PMID- 25110536
TI - Effect of sitagliptin on lipid profile in patients with type 2 diabetes mellitus.
AB - BACKGROUND: Animal studies have demonstrated that an inhibition of DPP-4 has an
impact on the secretion of cholesterol and apoB by the small intestine. However,
there is no consensus about the changes of the lipid profile following
administration of sitagliptin. METHODS: Accordingly, we treated patients who had
type 2 diabetes complicated by dyslipidemia with sitagliptin and evaluated its
effects on the profile of lipid parameters. A total of 248 outpatients with type
2 diabetes complicated by dyslipidemia were treated with sitagliptin at a daily
dose of 50 mg. The levels and percent changes of lipid and glucose metabolism
markers were measured at baseline and at 12 weeks after the initiation of
treatment. RESULTS: Both plasma glucose and HbA1c were significantly decreased.
Among the lipid parameters, total cholesterol (TC) and non-high-density
lipoprotein cholesterol (non-HDL-C) showed a significant decrease (TC 3.6+/
15.6%, non-HDL-C 2.9+/-19.7%; P < 0.05). Stratified analysis revealed a
significant decrease of TC, low-density lipoprotein cholesterol (LDL-C) and non
HDL-C in the high triglyceride (TG) group (>= 150 mg/dL) (P < 0.05). Analysis
stratified by demographic factors demonstrated significant differences in the
changes of TC, LDL-C and non-HDL-C. Multivariate analysis showed a significant
decrease of the TC, LDL-C and non-HDL-C levels in the high TG group (>= 150
mg/dL), as well as a significant decrease of TC and LDL-C in patients using
strong statins. CONCLUSIONS: The results suggested that sitagliptin caused a
significant decrease of TC, LDL-C and non-HDL-C, particularly in patients with
high baseline TG levels and those using strong statins.
PMID- 25110537
TI - Psychological distress, personality traits and functional disability in patients
with osteonecrosis of the femoral head.
AB - BACKGROUND: The aim of the present study was to investigate personality traits,
psychological distress and functional disability in patients with non-traumatic
osteonecrosis of the femoral head (ONFH). METHODS: Sixty-seven patients
participated in the study, 48 males and 19 females. The mean age was 37.6 years
(SD: 10.92, range: 15 - 61). Seventy-five healthy individuals, age and sex
matched, served as controls. Socio-demographic information and clinical data were
collected. The following instruments were used: the General Health Questionnaire
(GHQ-28), the Defence Style Questionnaire (DSQ) and the World Health Organization
Disability Assessment Schedule II (WHO-DAS II). RESULTS: Patients suffering from
ONFH presented higher scores at the GHQ-28 compared to healthy controls (P <
0.001). Duration of disease (P < 0.047) and age (P < 0.023) were the main factors
associated with psychological distress (P < 0.003). Personality traits such as
image distorting (P < 0.025) and self-sacrificing (P < 0.029) were identified in
patients with ONFH compared to healthy controls. Functional disability was
associated with high scores at GHQ-28 scale (P < 0.001). The "adaptive
personality structure", as measured by DSQ was negatively associated with
functional impairment (P < 0.022). CONCLUSIONS: Patients with ONFH more commonly
present symptoms of psychological distress associated with distinct functional
clinical parameters. The present study also reveals the role of personality
traits. Further investigation could specify the possible influence of
psychopathology and personality traits or coping strategies on the course of
disease.
PMID- 25110538
TI - Risk factors for subclavian vein thrombosis in cancer patients with total
parenteral nutrition.
AB - BACKGROUND: There are few reports on total parenteral nutrition (TPN) and its
possible prothrombotic effect. The purpose of this study was to identify risk
factors for subclavian vein thrombosis (SVT) in patients receiving TPN. METHOD:
Cancer patients with indwelling subclavian catheters and TPN were followed in a
cohort study. Doppler ultrasound examination was performed 8 and 30 days after
catheter placement. RESULTS: One hundred twenty-one patients were included, with
a mean of 61 (+/- 11.8) years of age. We detected 36 SVT events at day 8 (29.8%)
and 47 (38.8%) at day 30 after central catheter placement. Mean length of
subclavian catheterization was 17.2 (+/- 8.2) days. Fifty-three point three
percent of patients receiving >= 3,050 mOsm TPN in 24 hours developed SVT
(relative risk (RR) = 2.01, 95% CI, 1.14 - 3.57; P = 0.016) at day 8 and 60% (RR
= 1.67, 95% CI, 1.30 - 2.71; P = 0.038) at day 30 post-catheter placement.
Protein administration of > 97.5 g/day was shown to be a risk factor for early
thrombosis with a mean of 16.88 days for the development of SVT (95% CI, 10 -
23.7) versus 27.8 days (95% CI, 25.8 - 29.9) in the group with nutritional
protein content < 97.5 g/day (P = 0.000). CONCLUSION: High-osmolarity and high
protein nutrition formulas were shown to be risk factors for SVT in cancer
patients receiving TPN.
PMID- 25110539
TI - Effect of statins on endothelial function in patients with acute coronary
syndrome: a prospective study using adhesion molecules and flow-mediated
dilatation.
AB - BACKGROUND: Accumulating evidence suggests that inflammatory mechanisms play a
central role in the development, progression and outcome of atherosclerosis.
Recent evidence suggests that statins improve anti-inflammatory, anti-thrombotic
and endothelial functions, along with their lipid-decreasing effects. We examined
the effect of statins on endothelial function using biochemical markers of
endothelial dysfunction and brachial artery flow-mediated dilatation (FMD).
METHODS: Thirty male patients presenting with acute coronary syndrome (ACS) and
26 age-matched healthy control subjects aged 40 - 60 years who were not on any
medication were enrolled in the study. The patient group was started on
atorvastatin (40 mg/day) without consideration of their low-density lipoprotein
(LDL)-cholesterol levels. Endothelin, sICAM and E-selectin from stored serum
samples were measured using commercially available enzyme-linked immunosorbant
assays (ELISAs). Endothelial function was assessed using brachial artery FMD.
RESULTS: Prior to statin treatment, E-selectin, sICAM and endothelin levels,
endothelial dysfunction markers, were 99.74 +/- 34.67 ng/mL, 568.8 +/- 149.0
ng/mL and 0.62 +/- 0.33 fmol/mL, respectively in the patient group. E-selectin
and sICAM levels were significantly higher in the patients than in the control
subjects (P < 0.001); however, endothelin levels were not significantly different
between groups. Statin treatment significantly reduced E-selectin and sICAM
levels (P < 0.001); however, the decrease in endothelin levels was not
statistically significant. %FMD values were significantly increased after statin
treatment (P = 0.005), and levels of C-reactive protein (CRP), an inflammation
marker, were significantly reduced. CONCLUSION: Our results indicate that statins
play an important role in treatment endothelial dysfunction by reducing adhesion
of inflammatory cells.
PMID- 25110540
TI - Quality of life of patients after an acute coronary event: hospital discharge.
AB - BACKGROUND: The acute coronary syndrome (ACS) has a high morbi-mortality rate,
including physical deficiencies and functional limitations with impact on quality
of life. Cardiovascular rehabilitation 1 (CVR1) should begin as early as
possible, to enable improvement in functional capacity and quality of life.
Previous studies have shown association of cardiovascular diseases with quality
of life, in which depression and anxiety are the domains most altered. The aim of
the study is to verify the impact of an acute coronary event on quality of life
at the moment of hospital discharge. METHODOLOGY: This was a cross-sectional
study, with ACS patients hospitalized in ICU of a private hospital in the city of
Salvador, Brazil, submitted to CVR1. The quality of life questionnaire Euroqol-5D
was applied on discharge from hospital. Patients included in the study were those
with ACV, who had medical permission to walk, had not been submitted to acute
surgical treatment, were time and space oriented, and over the age of 18 years.
Patients excluded from the study were those with cognitive, orthopedic and
neurological problems, who used orthesis on a lower limb, and were in any
condition of risk at the time of beginning with CVR1. Data were collected by a
previously trained ICU team. RESULTS: Data were collected of 63 patients who
revealed compromise in the domains of pain/feeling ill (20.63%) and
anxiety/depression (38.09%). Statistical significance was observed in the
association between sex and pain/feeling ill (P < 0.01), sex and
anxiety/depression (P < 0.01), diabetes and mobility (P < 0.01), hereditary
factors and anxiety/depression (p < 0.01), BMI and pain/feeling ill (P < 0.01).
CONCLUSION: In this sample of patients, on discharge from hospital after ACS, the
pain/feeling ill and anxiety/depression domains were shown to be compromised.
PMID- 25110541
TI - Accuracy of unstimulated Basal serum thyroglobulin levels in assessing the
completeness of thyroidectomy.
AB - BACKGROUND: Complete excision is important for proper surgical treatment of
thyroid disorders. Functional thyroid tissue can be identified based on the level
of serum thyroglobulin (Tg), which is produced only by the thyroid follicular
cells, and nuclear scan. METHODS: Serum thyroid stimulating hormone (TSH), free
thyroxin (FT4), basal (unstimulated) Tg and anti-Tg antibody (anti-Tg ab) were
measured at the sixth postoperative month in 100 patients with benign thyroid
disorders treated by total thyroidectomy. Thyroid nuclear scan was obtained to
identify functional remnant of the thyroid gland. The sensitivity, specificity,
accuracy, positive predictive value (PPV) and negative predictive value (NPV) of
the Tg levels in assessing thyroid remnant were calculated. RESULTS: Positive
scan showed thyroid remnant in 23 patients, among whom 16 were Tg positive (true
positive) and seven were Tg negative (< 0.5 ng/mL) (false negative). In these
patients, the nuclear scan revealed pyramidal lobe remnants. In 77 patients with
negative scan, the Tg levels were also negative (true negative), and the PPV,
NPV, sensitivity, specificity and accuracy of the Tg levels were 100%, 92%, 70%,
100% and 93%, respectively. CONCLUSIONS: The positive basal Tg (> 0.5 ng/mL)
level accurately indicated the functional thyroid remnant after total
thyroidectomy. The negative Tg (< 0.5 ng/mL) level supported complete excision of
the thyroid gland. The surgical completeness of total thyroidectomy was
accurately evaluated based on the serum Tg levels. Therefore, serum Tg levels
should be measured in postoperative follow-up to determine the completeness of
total thyroidectomy.
PMID- 25110542
TI - Validation of the edinburgh postpartum depression scale in a population of adult
pregnant women in Mexico.
AB - BACKGROUND: The Edinburgh postnatal depression scale (EPDS) is useful for
screening depression in puerperal women as well as women during pregnancy.
However, such instrument should be validated in a given language before it can be
used. There is not validated Mexican version of the EPDS for use in adult
pregnant women. Therefore, we sought to validate a Spanish translated Mexican
version of the EPDS in a population of adult pregnant women. METHODS: One hundred
fifty-eight adult women (mean age: 28 +/- 6.8 years; range: 18 - 45 years) within
their 2 - 9 months of pregnancy attending routine prenatal consultations in a
public hospital in Durango City, Mexico were studied. All pregnant women
submitted a Spanish translated Mexican version of the EPDS. In addition,
participants were assessed for major and minor depression by using the DSM-IV
criteria. RESULTS: Of the 158 pregnant women studied, 11 had major depression and
26 had minor depression by the DSM-IV criteria. The best EPDS score for screening
combined major and minor depression in adult pregnant women was 9/10. This
threshold showed a sensitivity of 75.7%, a specificity of 74.4%, a positive
predictive value of 50.8%, a negative predictive value of 94.7% and an area under
the curve of 0.89 (95% confidence interval: 0.71 - 1.06). CONCLUSION: The Mexican
version of the EPDS can be considered for screening depression in Mexican adult
pregnant women whenever a cut-off score of 9/10 is used.
PMID- 25110543
TI - Chronic subdural hematoma in patients over 90 years old in a super-aged society.
AB - BACKGROUND: Chronic subdural hematoma (CSDH) is one of the most common diseases
in neurosurgical practice, particularly among aged patients. With the continuing
increase in the aged population, further increases in incidence are expected.
However, few studies have focused on CSDH in super-aged patients over 90 years
old. METHODS: We retrospectively reviewed medical records for 20 consecutive
patients over 90 years old with CSDH treated in our department between 2007 and
2013. The diagnosis of CSDH was confirmed by computed tomography (CT). Patients
were divided into a surgery group and a conservative group. Surgical procedures
included burr-hole surgery followed by insertion of a subdural drain under local
anesthesia. Clinical data were compared and analyzed. Neurological status was
evaluated according to the modified Rankin Scale at three time points: before
suffering from CSDH; at the time of referral or admission to our department; and
at discharge or 1 month after the first referral. Statistical tests were used to
analyze data and values of P < 0.05 were considered significant. RESULTS: Mean
age for the 20 cases was 92.6 years (range, 90 - 96 years). The leading symptoms
in this population were hemiparesis and gait disturbance, followed by disturbance
of consciousness and speech disturbance. Twelve patients underwent burr-hole
surgery. Mean maximum thickness of subdural hematoma as measured on CT was
significantly higher in the surgery group (28.2 +/- 5.4 mm) than in the
conservative group (17.0 +/- 3.8 mm; P < 0.01). Postoperatively, mean
neurological status was significantly improved in the surgery group (P < 0.01).
After surgery, 66.7% of patients could return home directly from hospital. No
significant perioperative complications directly related to surgery were
encountered in the surgery group, except for transient postoperative restlessness
and bruising of extremities due to falls. CONCLUSIONS: Surgery for CSDH is safe
and positively recommended even in super-aged patients over 90 years old if the
patient's physical status is fair. Pre-illness status is the most important
factor for considering operative indications and represents a limiting factor for
postoperative outcomes in this age population.
PMID- 25110544
TI - Does modification to the approach to contacting potential participants improve
recruitment to clinical trials?
AB - BACKGROUND: It is critical that clinical trial researchers ensure efficient and
successful patient recruitment. Recruitment is often slower than expected and
required sample sizes not obtained within initial funding deadlines. There is
little rigorous evidence supporting ways to improve recruitment. We hypothesized
making telephone contact with subjects prior to hospital attendance would improve
recruitment rates into clinical trials. METHODS: Retrospective post hoc analysis
of recruitment rates in an on-going clinical trial was undertaken. Two hundred
twelve consecutive patients were recruited over 6 months. During the first 3
months, patients received a telephone call from the research team and also
received an information sheet by post prior to clinic attendance (group 1). The
study was discussed on telephone and any issues were re-addressed at the
patient's clinic appointment when they were formally invited to participate in
the study. After 3 months, the investigators stopped telephoning the patients
(group 2); patients were invited to participate in the study by post and were
first spoken to directly by an investigator in clinic. The study protocol and
investigators did not change between groups. RESULTS: There was no significant
difference in baseline demographics between the two groups. There was a
significant improvement in recruitment rate in group 1 compared to group 2 (77.7%
vs. 45.0%, P < 0.0001). An improvement in clinic attendance rate in group 1 was
observed, although this was not significant (did not attend rate: 2.9% vs. 7.8%,
P = 0.14). CONCLUSION: Telephone contact between researchers and potential
participants prior to clinic attendance can greatly improve study recruitment
rates. This information may benefit the design of all clinical studies.
PMID- 25110545
TI - Recurrent arterial and venous thromboemboli as initial presentation of acute
promyelocytic leukemia.
AB - We report a case of a 52-year-old Caucasian woman diagnosed with a synchronic
arterial and venous thrombosis as an initial presentation of an acute
promyelocytic leukemia (APL). After the diagnosis, the patient was treated with
all trans-retinoic acid and arsenic chemotherapy concomitant to systemic
anticoagulation. This treatment regimen led to a complete remission and absence
of relapse of the thrombosis or APL during the follow-up. To our knowledge, this
presentation is the second case in the literature. We use this opportunity to
emphasize the importance of performing a complete medical evaluation in cases of
unusual thromboembolic events.
PMID- 25110546
TI - Potential biomarker for human uterine leiomyosarcoma.
PMID- 25110547
TI - Secondary polycythemia and the risk of venous thromboembolism.
PMID- 25110548
TI - Behavioral Attention: A Longitudinal Study of Whether and How It Influences the
Development of Word Reading and Reading Comprehension among At-Risk Readers.
AB - The purpose of this study was to examine the extent to which teacher ratings of
behavioral attention predicted responsiveness to word reading instruction in
first grade and third-grade reading comprehension performance. Participants were
110 first grade students identified as at-risk for reading difficulties who
received 20 weeks of intensive reading intervention in combination with classroom
reading instruction. Path analysis indicated that teacher ratings of student
attention significantly predicted students' word reading growth in first grade
even when they were competed against other relevant predictors (phonological
awareness, nonword reading, sight word efficiency, vocabulary, listening
comprehension, hyperactivity, nonverbal reasoning, and short term memory). Also,
student attention demonstrated a significant indirect effect on third grade
reading comprehension via word reading, but not via listening comprehension.
Results suggest that student attention (indexed by teacher ratings) is an
important predictor of at-risk readers' responsiveness to reading instruction in
first grade and that first-grade reading growth mediates the relationship between
students' attention and their future level of reading comprehension. The
importance of considering ways to manage and improve behavioral attention when
implementing reading instruction is discussed.
PMID- 25110549
TI - Atorvastatin represses the angiotensin 2-induced oxidative stress and
inflammatory response in dendritic cells via the PI3K/Akt/Nrf 2 pathway.
AB - Dendritic cells (DCs), which are highly proficient antigen-presenting cells, play
a complex role in both the initiation and progression of atherosclerosis. We
tested the hypothesis that the anti-inflammatory and antioxidant effects of
atorvastatin may be partly mediated by the phosphatidylinositol 3-kinase/protein
kinase B/transcription factor nuclear factor-erythroid 2-related factor 2
(PI3K/Akt/Nrf 2) pathway via the attenuation of DC maturation, thus reducing the
inflammatory and oxidative stress responses. This study showed that angiotensin 2
(Ang 2) induced the maturation of DCs, stimulated CD83, CD40, CD80, and CD86
expression, and increased the secretion of IL-12p70, IL-6, and TNF-alpha. These
effects were suppressed by atorvastatin. Atorvastatin also lowered the levels of
reactive oxygen species (ROS) and malondialdehyde (MDA), counteracting their
initial increases in response to Ang 2 stimulation. Atorvastatin activated Nrf 2
via the PI3K/Akt pathway and thereby promoted Nrf 2 translocation from the
cytoplasm to the nucleus in bone marrow-derived dendritic cells (BMDCs), a
process that was reversed by the PI3K inhibitor LY294002. Therefore, the
regulation of Nrf 2 expression by the PI3K/Akt pathway plays an important role in
the regulation of the statin-mediated antioxidant and anti-inflammatory responses
in DCs.
PMID- 25110550
TI - Oxidative stresses and mitochondrial dysfunction in age-related hearing loss.
AB - Age-related hearing loss (ARHL), the progressive loss of hearing associated with
aging, is the most common sensory disorder in the elderly population. The
pathology of ARHL includes the hair cells of the organ of Corti, stria
vascularis, and afferent spiral ganglion neurons as well as the central auditory
pathways. Many studies have suggested that the accumulation of mitochondrial DNA
damage, the production of reactive oxygen species, and decreased antioxidant
function are associated with subsequent cochlear senescence in response to aging
stress. Mitochondria play a crucial role in the induction of intrinsic apoptosis
in cochlear cells. ARHL can be prevented in laboratory animals by certain
interventions, such as caloric restriction and supplementation with antioxidants.
In this review, we will focus on previous research concerning the role of the
oxidative stress and mitochondrial dysfunction in the pathology of ARHL in both
animal models and humans and introduce concepts that have recently emerged
regarding the mechanisms of the development of ARHL.
PMID- 25110551
TI - Bovine beta-lactoglobulin/fatty acid complexes: binding, structural, and
biological properties.
AB - Ligand-binding properties of beta-lactoglobulin (beta-lg) are well documented,
but the subsequent biological functions are still unclear. Focusing on fatty
acids/beta-lg complexes, the structure-function relationships are reviewed in the
light of the structural state of the protein (native versus non-native aggregated
proteins). After a brief description of beta-lg native structure, the review
takes an interest in the binding properties of native beta-lg (localization of
binding sites, stoichiometry, and affinity) and the way the interaction affects
the biological properties of the protein and the ligand. The binding properties
of non-native aggregated forms of beta-lg that are classically generated during
industrial processing are also related. Structural changes modify the
stoichiometry and the affinity of beta-lg for fatty acids and consequently the
biological functions of the complex. Finally, the fatty acid-binding properties
of other whey proteins (alpha-lactalbumin, bovine serum albumin) and some
biological properties of the complexes are also addressed. These proteins affect
beta-lg/fatty acids complex in whey given their competition with beta-lg for
fatty acids.
PMID- 25110552
TI - Communicating clinical research to reduce cancer risk through diet: Walnuts as a
case example.
AB - Inflammation is one mechanism through which cancer is initiated and progresses,
and is implicated in the etiology of other conditions that affect cancer risk and
prognosis, such as type 2 diabetes, cardiovascular disease, and visceral obesity.
Emerging human evidence, primarily epidemiological, suggests that walnuts impact
risk of these chronic diseases via inflammation. The published literature
documents associations between walnut consumption and reduced risk of cancer, and
mortality from cancer, diabetes, and cardiovascular disease, particularly within
the context of the Mediterranean Diet. While encouraging, follow-up in human
intervention trials is needed to better elucidate any potential cancer prevention
effect of walnuts, per se. In humans, the far-reaching positive effects of a
plant-based diet that includes walnuts may be the most critical message for the
public. Indeed, appropriate translation of nutrition research is essential for
facilitating healthful consumer dietary behavior. This paper will explore the
translation and application of human evidence regarding connections with cancer
and biomarkers of inflammation to the development of dietary guidance for the
public and individualized dietary advice. Strategies for encouraging dietary
patterns that may reduce cancer risk will be explored.
PMID- 25110553
TI - Anti-inflammatory effect of methanol extract from Erigeron Canadensis L. may be
involved with upregulation of heme oxygenase-1 expression and suppression of
NFkappaB and MAPKs activation in macrophages.
AB - BACKGROUND/OBJECTIVES: In this study, we determined the anti-inflammatory
activities and the underlying molecular mechanisms of the methanol extract from
Erigeron Canadensis L. (ECM) in LPS-stimulated RAW264.7 macrophage cells.
MATERIALS/METHODS: The potential anti-inflammatory properties of ECM were
investigated by using RAW264.7 macrophages. We used western blot assays and real
time quantitative polymerase chain reaction to detect protein and mRNA
expression, respectively. Luciferase assays were performed to determine the
transactivity of transcription factors. RESULTS: ECM significantly inhibited
inducible nitric oxide synthase (iNOS)-derived NO and cyclooxygenase-2 (COX-2)
derived PGE2 production in LPS-stimulated RAW264.7 macrophages. These inhibitory
effects of ECM were accompanied by decreases in LPS-induced nuclear
translocations and transactivities of NFkappaB. Moreover, phosphorylation of
mitogen-activated protein kinase (MAPKs) including extracellular signal-related
kinase (ERK1/2), p38, and c-jun N-terminal kinase (JNK) was significantly
suppressed by ECM in LPS-stimulated RAW264.7 macrophages. Further studies
demonstrated that ECM by itself induced heme oxygenase-1 (HO-1) protein
expression at the protein levels in dose-dependent manner. However, zinc
protoporphyrin (ZnPP), a selective HO-1 inhibitor, abolished the ECM-induced
suppression of NO production. CONCLUSIONS: These results suggested that ECM
induced HO-1 expression was partly responsible for the resulting anti
inflammatory effects. These findings suggest that ECM exerts anti-inflammatory
actions and help to elucidate the mechanisms underlying the potential therapeutic
values of Erigeron Canadensis L.
PMID- 25110554
TI - The effect of long-term supplementation with different dietary omega-6/omega-3
ratios on mineral content and ex vivo prostaglandin E2 release in bone of growing
rabbits.
AB - BACKGROUND/OBJECTIVES: The aim of this research was to study the different long
term effects of consumption of dietary oil sources with varying omega-6/omega-3
(omega-6/omega-3) polyunsaturated fatty acids (PUFAs) ratios on bone marrow fatty
acid level, ex vivo prostaglandin E2 (PGE2) release, and mineral content of bone
in rabbits. MATERIALS/METHODS: For this purpose, weaning and female New Zealand
white rabbits were purchased and randomly divided into five groups and offered ad
libitum diets containing 70 g/kg of added oil for 100 days. The dietary lipid
treatments were formulated to provide the following ratios of omega-6/omega-3
fatty acids: 8.68 soy bean oil (SBO control), 21.75 sesame oil (SO), 0.39 fish
oil (FO), 0.63 algae oil (DHA), and 0.68 algae oils (DHA/ARA). DHA and ARA are
two types of marine microalgae of the genus Crypthecodinium cohnii. RESULTS: The
dietary treatments had significant effects on the bone marrow fatty acids of
rabbits. Rabbits fed the FO diet, containing the highest omega-3 PUFA
concentration, and those fed the SBO diet showed the highest omega-6 PUFA. On the
other hand, a positive correlation was observed between Ex vivo PGE2 level and
the omega-6/omega-3 dietary ratio. Significant effects of dietary treatment on
femur Ca, P, Mg, and Zn contents were observed in both genders. CONCLUSIONS:
Findings of the current study clearly demonstrated that dietary PUFA,
particularly omega-6/omega-3 and ARA/EPA ratios are important factors in
determining bone marrow fatty acid profile, and this in turn determines the
capacity of bone for synthesis of PGE2, thereby reducing bone resorption and
improving bone mass during growth.
PMID- 25110555
TI - Effects of lycopene on number and function of human peripheral blood endothelial
progenitor cells cultivated with high glucose.
AB - BACKGROUND/OBJECTIVES: The objectives of this study were to investigate the
effects of lycopene on the migration, adhesion, tube formation capacity, and p38
mitogen-activated protein kinase (p38 MAPK) activity of endothelial progenitor
cells (EPCs) cultivated with high glucose (HG) and as well as explore the
mechanism behind the protective effects of lycopene on peripheral blood EPCs.
MATERIALS/METHODS: Mononuclear cells were isolated from human peripheral blood by
Ficoll density gradient centrifugation. EPCs were identified after induction of
cellular differentiation. Third generation EPCs were incubated with HG (33
mmol/L) or 10, 30, and 50 ug/mL of lycopene plus HG. MTT assay and flow cytometry
were performed to assess proliferation and apoptosis of EPCs. EPC migration was
assessed by MTT assay with a modified boyden chamber. Adhesion assay was
performed by replating EPCs on fibronectin-coated dishes, after which adherent
cells were counted. In vitro vasculogenesis activity was assayed by Madrigal
network formation assay. Western blotting was performed to analyze protein
expression of both phosphorylated and non-phosphorylated p38 MAPK. RESULTS: The
proliferation, migration, adhesion, and in vitro vasculogenesis capacity of EPCs
treated with 10, 30, and 50 ug/mL of lycopene plus HG were all significantly
higher comapred to the HG group (P < 0.05). Rates of apoptosis were also
significantly lower than that of the HG group. Moreover, lycopene blocked
phosphorylation of p38 MAPK in EPCs (P < 0.05). To confirm the causal
relationship between MAPK inhibition and the protective effects of lycopene
against HG-induced cellular injury, we treated cells with SB203580, a
phosphorylation inhibitor. The inhibitor significantly inhibited HG-induced EPC
injury. CONCLUSIONS: Lycopene promotes proliferation, migration, adhesion, and in
vitro vasculogenesis capacity as well as reduces apoptosis of EPCs. Further, the
underlying molecular mechanism of the protective effects of lycopene against HG
induced EPC injury may involve the p38 MAPK signal transduction pathway.
Specifically, lycopene was shown to inhibit HG-induced EPC injury by inhibiting
p38 MAPKs.
PMID- 25110556
TI - Anti-proliferative and angio-suppressive effect of Stoechospermum marginatum (C.
Agardh) Kutzing extract using various experimental models.
AB - BACKGROUND/OBJECTIVES: Abundant consumption of seaweeds in the diet is
epidemiologically linked to the reduction in risk of developing cancer. In larger
cases, however, identification of particular seaweeds that are accountable for
these effects is still lacking, hindering the recognition of competent dietary
based chemo preventive approaches. The aim of this research was to establish the
antiproliferative potency and angiosuppressive mode of action of Stoechospermum
marginatum seaweed methanolic extract using various experimental models.
MATERIALS/METHODS: Among the 15 seaweeds screened for antiproliferative activity
against Ehrlich ascites tumor (EAT) cell line, Stoechospermum marginatum extract
(SME) was found to be the most promising. Therefore, it was further investigated
for its anti-proliferative activity in-vitro against choriocarcinoma (BeWo) and
non-transformed Human embryonic kidney (HEK 293) cells, and for its anti
migratory/tube formation activity against HUVEC cells in-vitro. Subsequently, the
angiosuppressive activity of S. marginatum was established by inhibition of
angiogenesis in in-vivo (peritoneal angiogenesis and chorioallantoic membrane
assay) and ex-vivo (rat cornea assay) models. RESULTS: Most brown seaweed
extracts inhibited the proliferation of EAT cells, while green and red seaweed
extracts were much less effective. According to the results, SME selectively
inhibited proliferation of BeWo cells in-vitro in a dose-dependent manner, but
had a lesser effect on HEK 293 cells. SME also suppressed the migration and tube
formation of HUVEC cells in-vitro. In addition, SME was able to suppress VEGF
induced angiogenesis in the chorio allantoic membrane, rat cornea, and tumor
induced angiogenesis in the peritoneum of EAT bearing mice. A decrease in the
microvessel density count and CD31 antigen staining of treated mice peritoneum
provided further evidence of its angiosuppressive activity. CONCLUSIONS:
Altogether, the data underline that VEGF mediated angiogenesis is the target for
the angiosuppressive action of SME and could potentially be useful in cancer
prevention or treatment involving stimulated angiogenesis.
PMID- 25110557
TI - Protective effects of Acanthopanax divaricatus extract in mouse models of
Alzheimer's disease.
AB - BACKGROUND: Acanthopanax divaricatus var. albeofructus (ADA) extract has been
reported to have anti-oxidant, immunomodulatory, and anti-mutagenic activity.
MATERIALS/METHODS: We investigated the effects of ADA extract on two mouse models
of Alzheimer's disease (AD); intracerebroventricular injection of beta-amyloid
peptide (Abeta) and amyloid precursor protein/presenilin 1 (APP/PS1)-transgenic
mice. RESULTS: Intra-gastric administration of ADA stem extract (0.25 g/kg, every
12 hrs started from one day prior to injection of Abeta1-42 until evaluation)
effectively blocked Abeta1-42-induced impairment in passive avoidance
performance, and Abeta1-42-induced increase in immunoreactivities of glial
fibrillary acidic protein and interleukin (IL)-1alpha in the hippocampus. In
addition, it alleviated the Abeta1-42-induced decrease in acetylcholine and
increase in malondialdehyde levels in the cortex. In APP/PS1-transgenic mice,
chronic oral administration of ADA stem extract (0.1 or 0.5 g/kg/day for six
months from the age of six to 12 months) resulted in significantly enhanced
performance of the novel-object recognition task, and reduced amyloid deposition
and IL-1beta in the brain. CONCLUSIONS: The results of this study suggest that
ADA stem extract may be useful for prevention and treatment of AD.
PMID- 25110558
TI - Apple pectin, a dietary fiber, ameliorates myocardial injury by inhibiting
apoptosis in a rat model of ischemia/reperfusion.
AB - BACKGROUND/OBJECTIVE: Myocardial cell death due to occlusion of the coronary
arteries leads to myocardial infarction, a subset of coronary heart disease
(CHD). Dietary fiber is known to be associated with a reduced risk of CHD, the
underlying mechanisms of which were suggested to delay the onset of occlusion by
ameliorating risk factors. In this study, we tested a hypothesis that a
beneficial role of dietary fiber could arise from protection of myocardial cells
against ischemic injury, manifested after occlusion of the arteries.
MATERIALS/METHODS: Three days after rats were fed apple pectin (AP) (with 10, 40,
100, and 400 mg/kg/day), myocardial ischemic injury was induced by 30 min
ligation of the left anterior descending coronary artery, followed by 3 hr
reperfusion. The area at risk and infarct area were evaluated using Evans blue
dye and 2,3,5-triphenyltetrazolium chloride (TTC) staining, respectively. DNA
nicks reflecting the extent of myocardial apoptosis were assessed by TUNEL assay.
Levels of cleaved caspase-3, Bcl-2, and Bax were assessed by
immunohistochemistry. RESULTS: Supplementation of AP (with 100 and 400 mg/kg/day)
resulted in significantly attenuated infarct size (IS) (ratio of infarct area to
area at risk) by 21.9 and 22.4%, respectively, in the AP-treated group, compared
with that in the control group. This attenuation in IS showed correlation with
improvement in biomarkers involved in the apoptotic cascades: reduction of
apoptotic cells, inhibition of conversion of procaspase-3 to caspase-3, and
increase of Bcl-2/Bax ratio, a determinant of cell fate. CONCLUSIONS: The
findings indicate that supplementation of AP results in amelioration of
myocardial infarction by inhibition of apoptosis. Thus, the current study
suggests that intake of dietary fiber reduces the risk of CHD, not only by
blocking steps leading to occlusion, but also by protecting against ischemic
injury caused by occlusion of the arteries.
PMID- 25110559
TI - Protective effect of the standardized green tea seed extract on UVB-induced skin
photoaging in hairless mice.
AB - BACKGROUND/OBJECTIVES: Ultraviolet B (UVB) irradiation on skin can induce
production of reactive oxygen species (ROS), which cause expression of matrix
metalloproteinases (MMPs) and collagen degradation. Thus, chronic exposure of
skin to UVB irradiation leads to histological changes consistent with aging, such
as wrinkling, abnormal pigmentation, and loss of elasticity. We investigated the
protective effect of the standardized green tea seed extract (GSE) on UVB-induced
skin photoaging in hairless mice. MATERIALS/METHODS: Skin photoaging was induced
by UVB irradiation on the back of Skh-1 hairless mice three times per week and
UVB irradiation was performed for 10 weeks. Mice were divided into six groups;
normal control, UVB irradiated control group, positive control (UVB + dietary
supplement of vitamin C 100 mg/kg), GSE 10 mg/kg (UVB + dietary supplement of GSE
10 mg/kg), GSE 100 mg/kg (UVB + dietary supplement of GSE 100 mg/kg), and GSE 200
mg/kg (UVB + dietary supplement of GSE 200 mg/kg). RESULTS: The dietary
supplement GSE attenuated UVB irradiation-induced wrinkle formation and the
decrease in density of dermal collagen fiber. In addition, results of the
antioxidant analysis showed that GSE induced a significant increase in
antioxidant enzyme activity compared with the UVB irradiation control group.
Dietary supplementation with GSE 200 mg/kg resulted in a significant decrease in
expression of MMP-1, MMP-3, and MMP-9 and an increase in expression of TIMP and
type-1 collagen. CONCLUSIONS: Findings of this study suggest that dietary
supplement GSE could be useful in attenuation of UVB irradiation-induced skin
photoaging and wrinkle formation due to regulation of antioxidant defense systems
and MMPs expression.
PMID- 25110560
TI - Effect of Hominis Placenta on cutaneous wound healing in normal and diabetic
mice.
AB - BACKGROUND/OBJECTIVES: The number of diabetic patients has recently shown a rapid
increase, and delayed wound healing is a major clinical complication in diabetes.
In this study, the wound healing effect of Hominis placenta (HP) treatment was
investigated in normal and streptozotocin-induced diabetic mice.
MATERIALS/METHODS: Four full thickness wounds were created using a 4 mm biopsy
punch on the dorsum. HP was injected subcutaneously at the middle region of the
upper and lower wounds. Wounds were digitally photographed and wound size was
measured every other day until the 14th day. Wound closure rate was analyzed
using CANVAS 7SE software. Wound tissues were collected on days 2, 6, and 14
after wounding for H/E, immunohistochemistry for FGF2, and Masson's trichrome
staining for collagen study. RESULTS: Significantly faster wound closure rates
were observed in the HP treated group than in normal and diabetes control mice on
days 6 and 8. Treatment with HP resulted in reduced localization of inflammatory
cells in wounded skin at day 6 in normal mice and at day 14 in diabetic mice (P <
0.01). Expression of fibroblast growth factor (FGF) 2 showed a significant
increase in the HP treated group on day 14 in both normal (P < 0.01) and diabetic
mice (P < 0.05). In addition, HP treated groups showed a thicker collagen layer
than no treatment groups, which was remarkable on the last day, day 14, in both
normal and diabetic mice. CONCLUSIONS: Taken together, HP treatment has a
beneficial effect on acceleration of cutaneous wound healing via regulation of
the entire wound healing process, including inflammation, proliferation, and
remodeling.
PMID- 25110561
TI - Improvement in metabolic parameters in obese subjects after 16 weeks on a
Brazilian-staple calorie-restricted diet.
AB - BACKGROUND/OBJECTIVES: The standard pattern of Brazilian food consumption is
based on the combination of rice and beans served together in the main meals.
This study assessed the effects of Brazilian-staple calorie-restricted (BS-diet)
dietary advice, with brown rice and beans, on metabolic parameters, body
composition, and food intake in overweight/obese subjects. SUBJECTS/METHODS:
Twentyseven subjects were randomly assigned to a conventional-type calorie
restricted diet (CT-diet) (n = 13) or a BS-diet (n = 14). Glucose metabolism,
lipid profile, anthropometric and body composition parameters, and food intake
were measured before and after 16 weeks. Paired t-tests/Wilcoxon tests were used
for comparison of differences from baseline and unpaired t-tests/Mann-Whitney
tests were used for comparison of differences between the groups. RESULTS: After
16 weeks, both groups showed reductions in weight and waist circumference (P <
0.02), and the BS-diet group showed a decrease in body fat (P = 0.0001), and
significant improvement in glucose metabolism (fasting plasma glucose, glucose
and insulin areas under the curve, Cederholm index, and HOMA2-%beta) (P <= 0.04)
and lipid profile (cholesterol, triacylglycerol, LDL-c, VLDL-c, and
cholesterol/HDL-c ratio) (P <= 0.05). In addition, the BS-diet group showed
significant improvement in HOMA2-%beta, compared to the CT-diet group (P = 0.03).
The BS-diet group also showed a significant reduction in energy, lipids,
carbohydrate, and cholesterol intake (P <= 0.04) and an increase in fiber intake
(P <= 0.001), while the CT-diet group showed a significant reduction in intake of
energy, macronutrients, PUFA, and cholesterol (P <= 0.002). CONCLUSIONS: These
results demonstrate the benefits of the BS-diet on metabolic parameters in obese
subjects.
PMID- 25110562
TI - Plasma adipocytokines and antioxidants-status in Korean overweight and obese
females with dyslipidemia.
AB - BACKGROUD/OBEJECTIVES: It is hypothesized that obese people with dyslipidemia is
more likely to have increased oxidative stress and decreased antioxidant status,
in comparison with the controls who were obese without dyslipidemia. Thus, the
aims of the present study were to determine the dietary intakes, plasma
adipokines, and antioxidative systems between obese with dyslipidemia and obese
without dyslipidemia were investigated. SUBJECTS/METHODS: Female subjects who
were between 20 and 55 years old, and whose BMI was 23 or greater were recruited.
Subjects who met the criteria of BMI >= 23, total cholesterol >= 200 mg/dL, LDL
cholesterol >= 130 mg/dL, and TG >= 110 mg/dL were categorized Obese with
dyslipidemia. Anthropometric measurements and blood biochemical tests were
conducted. The diet survey was conducted by a trained dietitian using two days of
24 hour dietary recall. The lipid peroxidation, the plasma total antioxidant
capacity (TAC), the activities of antioxidantive enzymes, and various
antioxidantive vitamins levels were determined. RESULTS: Plasma adiponectin and
leptin levels were also determined. There were no significant differences for
age, Body Mass index (BMI), and body fat (%), waist-size between two groups.
Obese with dyslipidemia had significantly high levels of total cholesterol,
triglyceride, LDL-cholesterol, the ratio of total cholesterol/HDL-C, and the
ratio of HDL-C/LDL-C, respectively. Blood alkaline phosphatase level was
statistically different between the two groups (P < 0.05). No statistical
significance in dietary intake between two groups was shown. In case of obese
with dyslipidemia group, the levels of GSH-Px (P < 0.05) and catalase (P < 0.05)
as well as adjusted blood retinol (P < 0.05) and tocopherol level (P < 0.05) were
significantly low. However, the plasma concentration of leptin was significantly
high (P < 0.05). CONCLUSIONS: Obesity with dyslipidemia was shown to have high
arthtrogenic index, depleted antioxidant status, and higher blood leptin levels
which suggest higher risks of oxidative stress and cardiovascular diseases.
PMID- 25110563
TI - Factors contributing to participation in food assistance programs in the elderly
population.
AB - BACKGROUND/OBJECTIVES: The study objectives were to examine the participation
rate in food assistance programs and explore the factors that contribute to such
participation among the Korean elderly population. SUBJECTS/METHODS: The study
sample comprised 3,932 respondents aged 65 years or older who were selected from
a secondary data set, the fourth Korean Welfare Panel Study (KoWePS). The
factors, related to participation in programs were examined based on the
predisposing, enabling and need factors of the help-seeking behavior model.
Multiple logistic regression analysis was used to select the best contributors
among the factors related to program participation. RESULTS: The predisposing
rate in food assistance programs was 8.5% (7.1% for men and 10.4% for women).
When all variables were included in the model, living without spouse, no formal
education, low income, having social security benefits and food insecurity in
elderly men, and age, low income, having social security benefits and feeling
poor in elderly women were significantly related to a higher tendency to program
participation. CONCLUSIONS: The predisposing and need factors, such as living
without spouse, low education level, food insecurity and feeling poor were
important for program participation, as well as enabling factors, such as
household income and social security benefits. A comprehensive approach
considering these factors to identify the target population for food assistance
programs is needed to increase the effectiveness and target population
penetration of these programs.
PMID- 25110564
TI - Structural relations of late night snacking choice attributes and health
promotion behaviors according to dietary style of industrial workers.
AB - BACKGROUND/OBJECTIVES: This research was conducted to develop a construct model
regarding the dietary style, late night snacking choice attributes and health
promotion behaviors of industrial workers. SUBJECTS/METHODS: The surveys were
collected during the period between January and February 2013. A statistical
analysis of 888 industrial workers was conducted using SPSS 12.0 for Windows and
SEM (Structural Equation Model) using AMOS (Analysis of Moment Structure) 5.0
statistics package. RESULTS: The results of the correlations between all
variables showed significant positive correlations (P < 0.05). Results of factors
analysis on dietary styles were categorized into five factors and health
promotion behaviors were categorized into four. The reliability of these findings
was supported by a Cronbach's alpha coefficient of 0.6 and higher for all other
factors. After obtaining the factors from processing an exploratory factor
analysis and the end results supported the validity. In an attempt to study the
late night snacking choice attributes in accordance to dietary styles and the
health promotion behaviors of industrial workers, a structural equation model was
constructed and analyzed. CONCLUSIONS: All tests proved the model satisfied the
recommended levels of the goodness on fit index, and thus, the overall research
model was proved to be appropriate.
PMID- 25110565
TI - Analysis of micromineral contents of school meals.
AB - BACKGROUND/OBJECTIVES: Korean ordinary diets are referred to be good for human
health in worldwide. However it is uncertain whether they provide microminerals
enough for growth and health of teenagers. A main purpose of this study was to
identify micromineral contents in school meals. MATERIALS/METHODS: The fifty
cuisines were collected from elementary schools and middle schools in Gyeongnam
area. The contents of Fe, Zn, Cu and Mn among microminerals were analyzed by
using ICP-OES method. Data were expressed as mean, standard deviation and range
value and linear regression analysis performed. RESULTS: Fe level of
Pangibuseotpaprika-salad was the highest among side-dishes (average 346.6 ug) and
Zn level of Sullung-tang was highest among soups (average 229.1 ug). Cu level of
Buchu-kimchi was the highest among kimchies (average 217.5 ug) and Mn level of
Gumeunkongyangnyum-gui was highest among side-dishes (average 198.4 ug).
Generally cooked-rices as main dish had relative smaller amounts of microminerals
than the other cuisines. The results showed that the ratio of Cu : Fe : Zn was
approximately 12 : 4 : 1 and the relationship between Fe versus Zn or Fe versus
Cu was significantly positive. CONCLUSION: Comparing to Korean Dietary
Recommended Intakes (KDRI) level, school meals provided not sufficient amount
(<25% DRI) of Fe, Zn or Mn, while they did excessive amount (>125% DRI) of Cu.
PMID- 25110566
TI - Association between high sensitivity C-reactive protein and dietary intake in
Vietnamese young women.
AB - BACKGROUND/OBJECTIVES: High sensitivity C-reactive protein (hsCRP) is a strong
independent predictor of future cardiovascular disease (CVD) risk. We evaluated
the relationship between hsCRP and dietary intake in apparently healthy young
women living in southern Vietnam. SUBJECTS/METHODS: Serum hsCRP was measured and
dietary intake data were obtained using the 1-day 24-hour recall method in women
(n = 956; mean age, 25.0 +/- 5.7 years) who participated in the International
Collaboration Study for the Construction of Asian Cohort of the Korean Genome and
Epidemiology Study (KoGES) in 2011. RESULTS: Women in the high risk group (> 3
mg/L) consumed fewer fruits and vegetables, total plant food, potassium, and
folate than those in the low risk group (< 1 mg/L). A multiple regression
analysis after adjusting for covariates revealed a significant negative
association between hsCRP and fruit and vegetable consumption. A logistic
regression analysis showed that the odds ratio (OR) of having a high hsCRP level
in women with the highest quartiles of consumption of fruits and vegetables [OR,
0.391; 95% confidence interval (CI), 0.190-0.807], potassium [OR, 0.425; 95% CI,
0.192-0.939] and folate [OR, 0.490; 95% CI, 0.249-0.964] were significantly lower
than those in the lowest quartiles. CONCLUSIONS: These results suggest that, in
young Vietnamese women, an increased consumption of fruit and vegetables might be
beneficial for serum hsCRP, a risk factor for future CVD events.
PMID- 25110567
TI - The relationship of dietary sodium, potassium, fruits, and vegetables intake with
blood pressure among Korean adults aged 40 and older.
AB - BACKGROUND/OBJECTIVES: The inverse relationships of combined fruits and
vegetables intake with blood pressure have been reported. However, whether there
are such relationships with salty vegetables has rarely been investigated in
epidemiologic studies. We evaluated the relation of combined and separate intake
of fruits, vegetable intakes, and salty vegetables, as well as sodium and
potassium, with blood pressure among the middle-aged and elderly populations.
SUBJECTS/METHODS: The present cross-sectional analysis of a prospective cohort
baseline survey was performed with 6,283 subjects (2,443 men and 3,840 women) and
free of hypertension, diabetes, cardiovascular diseases, and cancer. Dietary data
were collected by trained interviewers using food frequency questionnaire.
RESULTS: The significantly inverse linear trend of diastolic blood pressure (DBP)
was found in fruits and non-pickled vegetables (81.2 mmHg in the lowest quintile
vs 79.0 mmHg in the highest quintile, P for trend = 0.0040) and fruits only (80.9
mmHg in the lowest quintile vs 79.4 mmHg in the highest quintile, P for trend =
0.0430) among men. In contrast, sodium and sodium to potassium ratio were
positively related with blood pressure among men (DBP, 78.8 mmHg in the lowest
quintile vs 80.6 mmHg in the highest quintile, P for trend = 0.0079 for sodium;
DBP, 79.0 mmHg in the lowest quintile vs 80.7 mmHg in the highest quintile, P for
trend = 0.0199 and SBP, 123.8 mmHg in the lowest quintile vs 125.9 mmHg in the
highest quintile for sodium/potassium). Kimchies consumption was positively
related to DBP for men (78.2 mmHg in the lowest quintile vs 80.9 mmHg in the
highest quintile for DBP, P for trend = 0.0003). Among women, these relations
were not found. CONCLUSION: Fruits and/or non-pickled vegetables may be
inversely, but sodium, sodium to potassium, and Kimchies may be positively
related to blood pressure among men.
PMID- 25110568
TI - Association between family structure and food group intake in children.
AB - BACKGROUNDS/OBJECTOVES: Family has an impact on dietary intake of children as a
proximal food environment and family structures are changing and becoming more
diverse. This study was performed to identify the association between family
structure and food group intake of children aged 3-18 years in Korea.
SUBJECTS/METHODS: A total of 3,217 children with complete data on variables for
household information, dietary intake and sampling weights were obtained from
2010-2011 Korea National Health and Nutrition Examination Survey. Children's
family structure was classified into 3 groups (Living with both parents, Living
with one parent and Living without parents). To evaluate children's food group
intake, scores of individual food groups ('Grains', 'Meat, Fish, Eggs and Beans',
'Vegetables', 'Fruits' and 'Milk and Dairy products') was calculated from percent
adherence to the recommended servings of the Korean Food Guidance System (KFGS).
'Food group mean score' was obtained by calculating the average of five food
group scores. RESULTS: After adjusting for age, sex, number of family members,
and household income, children living with both parents had higher scores in
'Fruits' (P < 0.01), 'Milk and Dairy products' (P < 0.05), and mean score of
individual food group score (P < 0.001) compared to children living with one
parent. Individual food group scores and mean scores of individual food group
scores were associated with different socio-demographic factors in study
children. Family structure was associated with 'Fruits,' 'Milk and Dairy
products' score and mean scores of food group scores. CONCLUSIONS: These results
suggested that different approach might be required to solve nutrition problem in
children depending on their family structure and other socio-demographic factors.
PMID- 25110569
TI - Moderate diet-induced weight loss is associated with improved insulin sensitivity
in middle-aged healthy obese Korean women.
AB - BACKGROUND/OBJECTIVE: The goal of the present study was to investigate the
effects of moderate caloric restriction on beta-cell function and insulin
sensitivity in middle-aged obese Korean women. SUBJECTS/METHODS: Fifty-seven
obese pre-menopausal Korean women participated in a 12-week calorie restriction
program. Data on total cholesterol (TC), high density lipoprotein cholesterol
(HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), and
fasting serum levels of glucose, insulin, C-peptide, blood pressure, leptin and
anthropometrics were collected. A dietary intake assessment was based on three
days of food recording. Additionally, beta-cell function [homeostasis model
assessment of beta-cell (HOMA-beta), insulinogenic index (ISI), C-peptide:glucose
ratio, and area under curve insulin/glucose (AUCins/glu)] and insulin sensitivity
[homeostasis model assessment for insulin resistance (HOMA-IR), Quantitative
insulin-sensitivity check index (QUICKI) and Matsuda index (MI)] were recorded.
RESULTS: When calories were reduced by an average of 422 kcal/day for 12 weeks,
BMI (-2.7%), body fat mass (-10.2%), and waist circumference (-5%) all decreased
significantly (P < 0.05). After calorie restriction, weight, body fat percentage,
hip circumference, BP, TC, HDL-C, LDL-C, plasma glucose at fasting, insulin at
fasting and 120 min, AUCglu and the insulin area under the curve all decreased
significantly (all P < 0.05), while insulin sensitivity (HOMA-IR, QUICKI and
Matsuda index) measured by OGTT improved significantly (P < 0.01). CONCLUSIONS:
Moderate weight loss due to caloric restriction with reduction in insulin
resistance improves glucose tolerance and insulin sensitivity in middle-aged
obese women and thereby may help prevent the development of type 2 diabetes
mellitus.
PMID- 25110570
TI - Relationships of adolescent's dietary habits with personality traits and food
neophobia according to family meal frequency.
AB - BACKGROUND: A higher frequency of family meals is associated with good dietary
habits in young people. This study focused on the relationships of family meal
frequency with food neophobia and personality traits in adolescents.
SUBJECTS/METHOD: For this purpose, we administered a survey to 495 middle school
students in Seoul metropolitan city, after which the data were analyzed using the
SPSS (18.0) program. Pearson correlation was used to determine the relationships
among dietary habits, personality traits, and food neophobia according to
frequency of family meals. RESULTS: Dietary habits, personality traits, and food
neophobia all showed significant differences according to the frequency of family
meals. Further, eating regular family meals was associated with good dietary
habits (P < 0.001) and was linked with improved extraversion, agreeableness,
conscientiousness, emotional stability, and openness/intellect (P < 0.001). On
the other hand, it showed a negative relationship with food neophobia (P <
0.001). The relationship between dietary habits and food neophobia showed a
negative correlation (P < 0.01). The relationship between dietary habits and
personality traits showed a positive correlation (P < 0.01). Lastly, the
relationship between personality traits and food neophobia showed a negative
correlation (P < 0.01). CONCLUSION: Based on the results of the study, the
frequency of family meals affects dietary habits, personality traits, and food
neophobia in adolescents.
PMID- 25110571
TI - Antifungal Amphiphilic Aminoglycosides.
AB - The attachment of alkyl and other hydrophobic groups to traditional antibacterial
kanamycins and neomycins creates amphiphilic aminoglycosides with altered
antimicrobial properties. In this review, we summarize the discovery of
amphiphilic kanamycins that are antifungal, but not antibacterial, and that
inhibit the growth of fungi by perturbation of plasma membrane functions. With
low toxicities against plant and mammalian cells, they appear to specifically
target the fungal plasma membrane. These new antifungal agents offer new options
for fighting fungal pathogens and are examples of reviving old drugs to confront
new therapeutic challenges.
PMID- 25110572
TI - Nebulin interactions with actin and tropomyosin are altered by disease-causing
mutations.
AB - BACKGROUND: Nemaline myopathy (NM) is a rare genetic muscle disorder, but one of
the most common among the congenital myopathies. NM is caused by mutations in at
least nine genes: Nebulin (NEB), alpha-actin (ACTA1), alpha-tropomyosin (TPM3),
beta-tropomyosin (TPM2), troponin T (TNNT1), cofilin-2 (CFL2), Kelch repeat and
BTB (POZ) domain-containing 13 (KBTBD13), and Kelch-like family members 40 and 41
(KLHL40 and KLHL41). Nebulin is a giant (600 to 900 kDa) filamentous protein
constituting part of the skeletal muscle thin filament. Around 90% of the primary
structure of nebulin is composed of approximately 35-residue alpha-helical
domains, which form super repeats that bind actin with high affinity. Each super
repeat has been proposed to harbor one tropomyosin-binding site. METHODS: We
produced four wild-type (WT) nebulin super repeats (S9, S14, S18, and S22), 283
to 347 amino acids long, and five corresponding repeats with a patient mutation
included: three missense mutations (p.Glu2431Lys, p.Ser6366Ile, and p.Thr7382Pro)
and two in-frame deletions (p.Arg2478_Asp2512del and p.Val3924_Asn3929del). We
performed F-actin and tropomyosin-binding experiments for the nebulin super
repeats, using co-sedimentation and GST (glutathione-S-transferase) pull-down
assays. We also used the GST pull-down assay to test the affinity of WT nebulin
super repeats for WT alpha- and beta-tropomyosin, and for beta-tropomyosin with
six patient mutations: p.Lys7del, p.Glu41Lys, p.Lys49del, p.Glu117Lys,
p.Glu139del and p.Gln147Pro. RESULTS: WT nebulin was shown to interact with actin
and tropomyosin. Both the nebulin super repeats containing the p.Glu2431Lys
mutation and nebulin super repeats lacking exon 55 (p.Arg2478_Asp2512del) showed
weak affinity for F-actin compared with WT fragments. Super repeats containing
the p.Ser6366Ile mutation showed strong affinity for actin. When tested for
tropomyosin affinity, super repeats containing the p.Glu2431Lys mutation showed
stronger binding than WT proteins to tropomyosin, and the super repeat containing
the p.Thr7382Pro mutation showed weaker binding than WT proteins to tropomyosin.
Super repeats containing the deletion p.Val3924_Asn3929del showed similar
affinity for actin and tropomyosin as that seen with WT super repeats. Of the
tropomyosin mutations, only p.Glu41Lys showed weaker affinity for nebulin (super
repeat 18). CONCLUSIONS: We demonstrate for the first time the existence of
direct tropomyosin-nebulin interactions in vitro, and show that nebulin
interactions with actin and tropomyosin are altered by disease-causing mutations
in nebulin and tropomyosin.
PMID- 25110573
TI - Seizure evoked regulation of LIM-HD genes and co-factors in the postnatal and
adult hippocampus.
AB - The LIM-homeodomain (LIM-HD) family of transcription factors is well known for
its functions during several developmental processes including cell fate
specification, cell migration and axon guidance, and its members play fundamental
roles in hippocampal development. The hippocampus is a structure that displays
striking activity dependent plasticity. We examined whether LIM-HD genes and
their co-factors are regulated during kainic acid induced seizure in the adult
rat hippocampus as well as in early postnatal rats, when the hippocampal
circuitry is not fully developed. We report a distinct and field-specific
regulation of LIM-HD genes Lhx1, Lhx2, and Lhx9, LIM-only gene Lmo4, and cofactor
Clim1a in the adult hippocampus after seizure induction. In contrast none of
these genes displayed altered levels upon induction of seizure in postnatal
animals. Our results provide evidence of temporal and spatial seizure mediated
regulation of LIM-HD family members and suggest that LIM-HD gene function may be
involved in activity dependent plasticity in the adult hippocampus.
PMID- 25110574
TI - Prism adaptation does not alter configural processing of faces.
AB - Patients with hemispatial neglect ('neglect') following a brain lesion show
difficulty responding or orienting to objects and events on the left side of
space. Substantial evidence supports the use of a sensorimotor training technique
called prism adaptation as a treatment for neglect. Reaching for visual targets
viewed through prismatic lenses that induce a rightward shift in the visual image
results in a leftward recalibration of reaching movements that is accompanied by
a reduction of symptoms in patients with neglect. The understanding of prism
adaptation has also been advanced through studies of healthy participants, in
whom adaptation to leftward prismatic shifts results in temporary neglect-like
performance. Interestingly, prism adaptation can also alter aspects of non
lateralised spatial attention. We previously demonstrated that prism adaptation
alters the extent to which neglect patients and healthy participants process
local features versus global configurations of visual stimuli. Since deficits in
non-lateralised spatial attention are thought to contribute to the severity of
neglect symptoms, it is possible that the effect of prism adaptation on these
deficits contributes to its efficacy. This study examines the pervasiveness of
the effects of prism adaptation on perception by examining the effect of prism
adaptation on configural face processing using a composite face task. The
composite face task is a persuasive demonstration of the automatic global-level
processing of faces: the top and bottom halves of two familiar faces form a
seemingly new, unknown face when viewed together. Participants identified the top
or bottom halves of composite faces before and after prism adaptation.
Sensorimotor adaptation was confirmed by significant pointing aftereffect,
however there was no significant change in the extent to which the irrelevant
face half interfered with processing. The results support the proposal that the
therapeutic effects of prism adaptation are limited to dorsal stream processing.
PMID- 25110575
TI - Nasal decongestant and chronic headache: a case of naphazoline overuse headache?
AB - BACKGROUND: Chronic headache is an incapacitating condition afflicting patients
at least for 15 days per month. In the most cases it is developed as a
consequence of an excessive use of symptomatic drugs. CASE: Here we report the
case of a 34 year-old man suffering from chronic headache possibly related to the
overuse of naphazoline nitrate nasal decongestant, used to treat a supposed
chronic sinusitis. However, the patient did not suffer from sinusitis, but from a
medication overuse headache (ICHD-II 8.3; ICD-10 44.41) that appeared to be due
to excessive use of naphazoline. CONCLUSION: The use of naphazoline nitrate may
result in an analgesic effect upon first use, through activation of adrenergic
and opioidergic systems, followed by a pro-migraine effect via a late induction
of an inflammatory cascade, modulated by nitric oxide and arachidonic acid. The
observation that naphazoline detoxification relieved the patient's headache,
indicates that prolonged use of naphazoline may cause chronic headaches.
Therefore, physicians should ask for details on the use of nasal decongestants in
patients complaining of chronic headache, as they could potentially be suffering
from a medication-overuse headache.
PMID- 25110576
TI - Functional characterization of Candida albicans Hos2 histone deacetylase.
AB - Candida albicans is a mucosal commensal organism in normal individuals, but is a
major pathogen causing systemic and mucosal infections in immunocompromised
individuals. Azoles have been very effective anti-fungal agents and the mainstay
in treating opportunistic mold and yeast infections. Azole resistant strains have
emerged compromising the utility of this class of drugs. It has been shown that
azole resistance can be reversed by the co-administration of a histone
deacetylase (HDAC) inhibitor, suggesting that resistance is mediated by
epigenetic mechanisms possibly involving Hos2, a fungal deacetylase. We report
here the cloning and functional characterization of HOS2 (High Osmolarity
Sensitive) , a gene coding for fungal histone deacetylase from C. albicans.
Inhibition studies showed that Hos2 is susceptible to pan inhibitors such as
trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), but is not
inhibited by class I inhibitors such MS-275. Purified Hos2 protein consistently
deacetylated tubulins, rather than histones from TSA-treated cells. This in vitro
enzymatic assay, which is amenable to high throughput could be used for screening
potent fungal Hos2 inhibitors that could be a potential anti-fungal adjuvant.
Hos2 has been reported to be a putative NAD+ dependent histone deacetylase, a
feature of sirtuins. We assayed for sirtuin activation with resveratrol and
purified Hos2 protein and did not find any sirtuin activity.
PMID- 25110577
TI - Accumulation of oocytes and/or embryos by vitrification: a new strategy for
managing poor responder patients undergoing pre implantation diagnosis.
AB - BACKGROUND: Low (or poor) responder patients are women who require large doses of
stimulation medications and produce less than an optimal number of oocytes during
IVF cycles. Low responder patients produce few oocytes and embryos, which
significantly reduces their chances for success in a preimplantation genetic
diagnosis (PGD) cycle. Accumulation of vitrified oocytes or embryos before the
actual PGD cycle is a possible strategy that might increase patient's chances for
a healthy pregnancy. AIM OF THE STUDY: This retrospective study evaluates the
efficacy of a PGD program in low responder patients after repeated ovarian
stimulation cycles with cumulative vitrification of oocytes and embryos. METHODS:
Over a period of 30 months, 13 patients entering the PGD program were identified
as poor responders after their first ovarian stimulation. These patients started
a PGD cycle for one of the following indications: history of recurrent
implantation failure (n=1), cystic fibrosis (n=1), X-linked microtubular myopathy
(n=1), recurrent miscarriages (n=5), Duchene muscular dystrophy (n=1),
chromosomal translocation (n=1) and high sperm aneuploidy (n=1). After multiple
ovarian hormonal stimulations patients had either all mature oocytes (Group A; 3
patients) or all of their day 2 embryos vitrified (group B; 10 patients). Mean
total number of oocyte collections per patient was 2.3 (range: 2 - 5 cycles).
RESULTS: In the actual PGD cycle, all vitrified oocytes from group A patients
were warmed and underwent intra cytoplasmic sperm injection (ICSI) followed by
culture up to day 3. For group B patients all vitrified day 2 embryos were warmed
and cultured overnight. On day 3 of culture, all embryos from Group A and B had
blastomere biopsy followed by genetic analysis. In group A, 20 embryos were found
suitable for biopsy and genetic analysis; at least one healthy embryo was
available for transfer for each patient. For group B, 72 embryos in total were
available for biopsy and PGD. All patients, except one, had at least one healthy
day 5 embryo for transfer (mean number of 2.1 embryos per transfer). Nine
patients had a clinical pregnancy; 7 patients delivered a healthy baby.
CONCLUSION: Low responder patients entering a PGD program might increase their
chances for a healthy pregnancy by repeat ovarian stimulation in combination with
cumulative oocyte or embryo vitrification.
PMID- 25110578
TI - C-Sibelia: an easy-to-use and highly accurate tool for bacterial genome
comparison.
AB - We present C-Sibelia, a highly accurate and easy-to-use software tool for
comparing two closely related bacterial genomes, which can be presented as either
finished sequences or fragmented assemblies. C-Sibelia takes as input two FASTA
files and produces: (1) a VCF file containing all identified single nucleotide
variations and indels; (2) an XMFA file containing alignment information. The
software also produces Circos diagrams visualizing high level genomic
architecture for rearrangement analyses. C-Sibelia is a part of the Sibelia
comparative genomics suite, which is freely available under the GNU GPL v.2
license at http://sourceforge.net/projects/sibelia-bio. C-Sibelia is compatible
with Unix-like operating systems. A web-based version of the software is
available at http://etool.me/software/csibelia.
PMID- 25110579
TI - Ten things to get right for marine conservation planning in the Coral Triangle.
AB - Systematic conservation planning increasingly underpins the conservation and
management of marine and coastal ecosystems worldwide. Amongst other benefits,
conservation planning provides transparency in decision-making, efficiency in the
use of limited resources, the ability to minimise conflict between diverse
objectives, and to guide strategic expansion of local actions to maximise their
cumulative impact. The Coral Triangle has long been recognised as a global marine
conservation priority, and has been the subject of huge investment in
conservation during the last five years through the Coral Triangle Initiative on
Coral Reefs, Fisheries and Food Security. Yet conservation planning has had
relatively little influence in this region. To explore why this is the case, we
identify and discuss 10 challenges that must be resolved if conservation planning
is to effectively inform management actions in the Coral Triangle. These are:
making conservation planning accessible; integrating with other planning
processes; building local capacity for conservation planning; institutionalising
conservation planning within governments; integrating plans across governance
levels; planning across governance boundaries; planning for multiple tools and
objectives; understanding limitations of data; developing better measures of
progress and effectiveness; and making a long term commitment. Most important is
a conceptual shift from conservation planning undertaken as a project, to
planning undertaken as a process, with dedicated financial and human resources
committed to long-term engagement.
PMID- 25110580
TI - Positioning a proned patient with cauda equina syndrome who presents at 15 weeks
gestation: a case report.
AB - Cauda equina syndrome is a neurosurgical emergency that requires prompt
intervention to prevent irreversible spinal cord paralysis. This article
describes how we managed a case of an obese pregnant patient who was placed in
the prone position for surgery. We discuss the evidence behind the management
options and choice of operating tables available.
PMID- 25110581
TI - Factors that contribute to social media influence within an Internal Medicine
Twitter learning community.
AB - Medical societies, faculty, and trainees use Twitter to learn from and educate
other social media users. These social media communities bring together
individuals with various levels of experience. It is not known if experienced
individuals are also the most influential members. We hypothesize that
participants with the greatest experience would be the most influential members
of a Twitter community. We analyzed the 2013 Association of Program Directors in
Internal Medicine Twitter community. We measured the number of tweets authored by
each participant and the number of amplified tweets (re-tweets). We developed a
multivariate linear regression model to identify any relationship to social media
influence, measured by the PageRank. Faculty (from academic institutions)
comprised 19% of the 132 participants in the learning community (p < 0.0001).
Faculty authored 49% of all 867 tweets (p < 0.0001). Their tweets were the most
likely to be amplified (52%, p < 0.01). Faculty had the greatest influence
amongst all participants (mean 1.99, p < 0.0001). Being a faculty member had no
predictive effect on influence (beta = 0.068, p = 0.6). The only factors that
predicted influence (higher PageRank) were the number of tweets authored (p <
0.0001) and number of tweets amplified (p < 0.0001) The status of "faculty
member" did not confer a greater influence. Any participant who was able to
author the greatest number of tweets or have more of his/her tweets amplified
could wield a greater influence on the participants, regardless of his/her
authority.
PMID- 25110582
TI - Tooth eruption sequence and dental crowding: a case-control study.
AB - When cases of dental crowding are identified and diagnosed promptly, interceptive
orthodontics is particularly successful. AIM: To assess the differences in the
eruption sequence of the mandibular canine and first premolar teeth in children
with and without dental crowding. MATERIALS AND METHODS: Children who attended
the Shiraz Dental School's orthodontic clinic (Iran) from September to December
2012 were enrolled in this case-control study. Tooth size arch length discrepancy
(TSALD) of all 8-10 year olds was calculated from patients' dental models. Thirty
six children were randomly selected from those with TSALD of equal or less than
4mm (those with crowding). Each selected case was matched for sex and age with
another child (as control) with TSALD>-4mm attending the same clinic, in the same
time period. The existing panoramic radiographs were traced and the eruption
percentages were measured for mandibular canine and first premolar teeth. The
mean difference between canine and first premolar eruption percentages was
compared between the case and control groups using the SPSS (version PASW 18)
software and a paired sample t-test. RESULTS: Canine and first premolar eruption
percentages in the case group were 65.82+/-13.00 and 78.92+/-10.15 percent,
respectively. The mean eruption percentages for canines and first premolars of
the control group were 74.12+/-14.55 and 75.47+/-11.60 percent, respectively.
There was a significant difference in pre-eruptive positions of canine and first
premolar teeth in those with moderate to severe crowding when compared to the
control group (p<0.001). CONCLUSION: These findings may improve the early
diagnosis of children with high risk of developing moderate to severe crowding
during mixed dentition.
PMID- 25110583
TI - Vitellogenin family gene expression does not increase Drosophila lifespan or
fecundity.
AB - One of the most striking patterns in comparative biology is the negative
correlation between lifespan and fecundity observed in comparisons among species.
This pattern is consistent with the idea that organisms need to allocate a fixed
energy budget among competing demands of growth, development, reproduction and
somatic maintenance. However, exceptions to this pattern have been observed in
many social insects, including ants, bees, and termites. In honey bees ( Apis
mellifera), Vitellogenin ( Vg), a yolk protein precursor, has been implicated in
mediating the long lifespan and high fecundity of queen bees. To determine if Vg
like proteins can regulate lifespan in insects generally, we examined the effects
of expression of Apis Vg and Drosophila CG31150 (a Vg-like gene recently
identified as cv-d) on Drosophila melanogaster lifespan and fecundity using the
RU486-inducible GeneSwitch system. For all genotypes tested, overexpression of Vg
and CG31150 decreased Drosophila lifespan and did not affect total or age
specific fecundity. We also detected an apparent effect of the GeneSwitch system
itself, wherein RU486 exposure (or the GAL4 expression it induces) led to a
significant increase in longevity and decrease in fecundity in our fly strains.
This result is consistent with the pattern reported in a recent meta-analysis of
Drosophila aging studies, where transgenic constructs of the UAS/GAL4 expression
system that should have no effect (e.g. an uninduced GeneSwitch) significantly
extended lifespan in some genetic backgrounds. Our results suggest that Vg-family
genes are not major regulators of Drosophila life history traits, and highlight
the importance of using appropriate controls in aging studies.
PMID- 25110584
TI - BridgeDb app: unifying identifier mapping services for Cytoscape.
AB - The BridgeDb app for Cytoscape allows users to map and annotate identifiers of
genes, proteins and metabolites in the context of biological networks. The app
greatly simplifies the identifier mapping process in Cytoscape by providing a
unified interface to different mapping resources and services. The app also
provides a programming interface via Cytoscape Commands that can be utilized for
identifier mapping by other Cytoscape apps. In this article we provide a
technical guide to the BridgeDb app for mapping identifiers in Cytoscape.
PMID- 25110585
TI - Global burden, distribution, and interventions for infectious diseases of
poverty.
AB - Infectious diseases of poverty (IDoP) disproportionately affect the poorest
population in the world and contribute to a cycle of poverty as a result of
decreased productivity ensuing from long-term illness, disability, and social
stigma. In 2010, the global deaths from HIV/AIDS have increased to 1.5 million
and malaria mortality rose to 1.17 million. Mortality from neglected tropical
diseases rose to 152,000, while tuberculosis killed 1.2 million people that same
year. Substantial regional variations exist in the distribution of these diseases
as they are primarily concentrated in rural areas of Sub-Saharan Africa, Asia,
and Latin America, with geographic overlap and high levels of co-infection.
Evidence-based interventions exist to prevent and control these diseases,
however, the coverage still remains low with an emerging challenge of
antimicrobial resistance. Therefore, community-based delivery platforms are
increasingly being advocated to ensure sustainability and combat co-infections.
Because of the high morbidity and mortality burden of these diseases, especially
in resource-poor settings, it is imperative to conduct a systematic review to
identify strategies to prevent and control these diseases. Therefore, we
attempted to evaluate the effectiveness of one of these strategies, that is
community-based delivery for the prevention and treatment of IDoP. In this paper,
we describe the burden, epidemiology, and potential interventions for IDoP. In
subsequent papers of this series, we describe the analytical framework and the
methodology used to guide the systematic reviews, and report the findings and
interpretations of our analyses of the impact of community-based strategies on
individual IDoPs.
PMID- 25110586
TI - Likelihoods for fixed rank nomination networks.
AB - Many studies that gather social network data use survey methods that lead to
censored, missing, or otherwise incomplete information. For example, the popular
fixed rank nomination (FRN) scheme, often used in studies of schools and
businesses, asks study participants to nominate and rank at most a small number
of contacts or friends, leaving the existence of other relations uncertain.
However, most statistical models are formulated in terms of completely observed
binary networks. Statistical analyses of FRN data with such models ignore the
censored and ranked nature of the data and could potentially result in misleading
statistical inference. To investigate this possibility, we compare Bayesian
parameter estimates obtained from a likelihood for complete binary networks with
those obtained from likelihoods that are derived from the FRN scheme, and
therefore accommodate the ranked and censored nature of the data. We show
analytically and via simulation that the binary likelihood can provide misleading
inference, particularly for certain model parameters that relate network ties to
characteristics of individuals and pairs of individuals. We also compare these
different likelihoods in a data analysis of several adolescent social networks.
For some of these networks, the parameter estimates from the binary and FRN
likelihoods lead to different conclusions, indicating the importance of analyzing
FRN data with a method that accounts for the FRN survey design.
PMID- 25110587
TI - Aqueous interleukin-6 levels are superior to vascular endothelial growth factor
in predicting therapeutic response to bevacizumab in age-related macular
degeneration.
AB - Objective. To prospectively evaluate the effect of intravitreal bevacizumab on
aqueous levels of interleukin-6 (IL-6) and vascular endothelial growth factor
(VEGF) in patients with exudative age-related macular degeneration (AMD) and
correlate clinical outcomes with cytokine levels. Methods. 30 eyes of 30 patients
with exudative AMD underwent intravitreal injection of bevacizumab three times at
monthly intervals. The aqueous samples prior to the 1st injection (baseline) and
3rd injection were analyzed for VEGF and IL-6 levels. Subjects were subgrouped
based upon change in the central subfield (CSF) macular thickness on SD-OCT at 8
weeks. Group 1 included patients (n = 14) with a decrease in CSF thickness
greater than 10% from the baseline (improved group). Group 2 included patients (n
= 16) who had a decrease in CSF thickness 10% or less (treatment-resistant).
Results. In subgroup analysis, in both groups 1 and 2 patients, compared to
aqueous VEGF, aqueous IL-6 levels showed a better correlation with CSF thickness
on SD-OCT (r = 0.72 and 0.71, resp.). Conclusions. Aqueous IL-6 may be an
important marker of treatment response or resistance in wet macular degeneration.
Future therapeutic strategies may include targeted treatment against both VEGF
and IL-6, in patients who do not respond to anti-VEGF treatment alone.
PMID- 25110588
TI - Construct validity and reliability of the adult rejection sensitivity
questionnaire: a comparison of three factor models.
AB - Objectives and Methods. The aim of the study was to investigate the construct
validity of the ARSQ. Methods. The ARSQ and self-report measures of depression,
anxiety, and hopelessness were administered to 774 Italian adults, aged 18 to 64
years. Results. Structural equation modeling indicated that the factor structure
of the ARSQ can be represented by a bifactor model: a general rejection
sensitivity factor and two group factors, expectancy of rejection and rejection
anxiety. Reliability of observed scores was not satisfactory: only 44% of
variance in observed total scores was due to the common factors. The analyses
also indicated different correlates for the general factor and the group factors.
Limitations. We administered an Italian version of the ARSQ to a nonclinical
sample of adults, so that studies which use clinical populations or the original
version of the ARSQ could obtain different results from those presented here.
Conclusion. Our results suggest that the construct validity of the ARSQ is
disputable and that rejection anxiety and expectancy could bias individuals to
readily perceive and strongly react to cues of rejection in different ways.
PMID- 25110589
TI - Antifungal susceptibility patterns, in vitro production of virulence factors, and
evaluation of diagnostic modalities for the speciation of pathogenic Candida from
blood stream infections and vulvovaginal candidiasis.
AB - Candida spp. have emerged as successful pathogens in both invasive and mucosal
infections. Varied virulence factors and growing resistance to antifungal agents
have contributed to their pathogenicity. We studied diagnostic accuracy of
HiCrome Candida Differential Agar and Vitek 2 Compact system for identification
of Candida spp. in comparison with species-specific PCR on 110 clinical isolates
of Candida from blood stream infections (54, 49%) and vulvovaginal candidiasis
(56, 51%). C. albicans (61%) was the leading pathogen in VVC, while C. tropicalis
(46%) was prominent among BSIs. HiCrome Agar and Vitek 2 Compact had good
measures of agreement (kappa) 0.826 and 0.895, respectively, in comparison with
PCR. We also tested these isolates for in vitro production of proteinase,
esterase, phospholipases, and biofilms. Proteinase production was more among
invasive isolates (P = 0.017), while phospholipase production was more among
noninvasive isolates (P = 0.001). There was an overall increase in the production
of virulence factors among non-albicans Candida. Identification of clinical
isolates of Candida up to species level either by chromogenic agar or by Vitek 2
Compact system should be routinely done to choose appropriate therapy.
PMID- 25110590
TI - External rotator sparing with posterior acetabular fracture surgery: does it
change outcome?
AB - This study analyses the results of the treatment with external rotator sparing
approach in acetabular fractures to determine whether muscle sparing has a
positive impact on functional outcome. 20 patients with a mean age of 45.9 years
(range: 26-64) that had been treated for displaced acetabular fractures were
included in this series. Short Musculoskeletal Function Assessment (SMFA)
questionnaire and hip muscle strength measurement were done at the 24-month of
follow-up period. The radiographic results at the final followup were excellent
in 9 hips (45%), good in 6 hips (30%), fair in 4 hips (20%), and poor in one hip
(5%) according to the criteria developed by Matta. The average SMFA score for all
of the patients was 18.3 (range: 0-55.4). The mean dysfunctional and bother
indexes were 17.2 and 20.6, respectively. The overall muscle strength deficit was
11.8%. The greatest loss of strength was in internal rotation. In patients with
better postoperative reduction quality of acetabular fracture, peak torque, and
maximum work of hip flexion, extension and also internal rotation maximum work
deficit were significantly lower (P < 0.05). Accurate initial reduction and
longer postoperative muscle strengthening exercise programs seem critical to
decrease postoperative hip muscle weakness after acetabular fractures.
PMID- 25110591
TI - Partial facetectomy for lumbar foraminal stenosis.
AB - Background. Several different techniques exist to address the pain and disability
caused by isolated nerve root impingement. Failure to adequately decompress the
lumbar foramen may lead to failed back surgery syndrome. However, aggressive
treatment often causes spinal instability or may require fusion for satisfactory
results. We describe a novel technique for decompression of the lumbar nerve root
and demonstrate its effectiveness in relief of radicular symptoms. Methods.
Partial facetectomy was performed by removal of the medial portion of the
superior facet in patients with lumbar foraminal stenosis. 47 patients underwent
the procedure from 2001 to 2010. Those who demonstrated neurogenic claudication
without spinal instability or central canal stenosis and failed conservative
management were eligible for the procedure. Functional level was recorded for
each patient. These patients were followed for an average of 3.9 years to
evaluate outcomes. Results. 27 of 47 patients (57%) reported no back pain and no
functional limitations. Eight of 47 patients (17%) reported moderate pain, but
had no limitations. Six of 47 patients (13%) continued to experience degenerative
symptoms. Five of 47 patients (11%) required additional surgery. Conclusions.
Partial facetectomy is an effective means to decompress the lumbar nerve root
foramen without causing spinal instability.
PMID- 25110594
TI - Myocardial Rupture following Carbon Monoxide Poisoning.
AB - We present the first case of severe cardiotoxicity of carbon monoxide leading to
myocardial rupture and fatal outcome. 83-year-old woman was hospitalized 4 hours
after the fire in her house with no respiratory or cardiac symptoms. After two
days, she has suffered sudden collapse leading to cardiac arrest. Postmortem
examination revealed intramural haemorrhage with myocardial rupture at the apex
of the left ventricle. Minimal stenosis was noted in the proximal coronary
arteries with no evidence of distal occlusion or any other long-standing heart
disease. This case supports recommendations for targeted cardiovascular
investigations in cases of CO poisoning.
PMID- 25110595
TI - Informed consent in otolaryngologic surgery: case scenario from a nigerian
specialist hospital.
AB - Informed consent is a foundational concept necessary for ethical conduct of
clinical research and practice. It is a technical tool that shifts the autonomy
to decide whether a medical procedure should be performed-from the doctor to the
patient. However there is an ongoing discussion in bioethical circles on the
level of comprehension of the informed consent process by the patients and
research participants. We present this case vignette and the discussion
afterwards to explore the question of to what extent a patient comprehends the
information given to him/her before a surgical procedure is carried out. In other
words, the question being asked here is how informed is informed consent in the
context of oto-laryngological practice.
PMID- 25110592
TI - Behavioral improvement and regulation of molecules related to neuroplasticity in
ischemic rat spinal cord treated with PEDF.
AB - Pigment epithelium derived factor (PEDF) exerts trophic actions to motoneurons
and modulates nonneuronal restorative events, but its effects on neuroplasticity
responses after spinal cord (SC) injury are unknown. Rats received a low thoracic
SC photothrombotic ischemia and local injection of PEDF and were evaluated
behaviorally six weeks later. PEDF actions were detailed in SC ventral horn
(motor) in the levels of the lumbar central pattern generator (CPG), far from the
injury site. Molecules related to neuroplasticity (MAP-2), those that are able to
modulate such event, for instance, neurotrophic factors (NT-3, GDNF, BDNF, and
FGF-2), chondroitin sulfate proteoglycans (CSPG), and those associated with
angiogenesis and antiapoptosis (laminin and Bcl-2) and Eph (receptor)/ephrin
system were evaluated at cellular or molecular levels. PEDF injection improved
motor behavioral performance and increased MAP-2 levels and dendritic processes
in the region of lumbar CPG. Treatment also elevated GDNF and decreased NT-3,
laminin, and CSPG. Injury elevated EphA4 and ephrin-B1 levels, and PEDF treatment
increased ephrin A2 and ephrins B1, B2, and B3. Eph receptors and ephrins were
found in specific populations of neurons and astrocytes. PEDF treatment to SC
injury triggered neuroplasticity in lumbar CPG and regulation of neurotrophic
factors, extracellular matrix molecules, and ephrins.
PMID- 25110596
TI - Axillary metastasis from an occult tubal serous carcinoma in a patient with
ipsilateral breast carcinoma: a potential diagnostic pitfall.
AB - Axillary nodal metastasis from a nonmammary neoplasia is much rarer than diseases
associated with a primary breast carcinoma. However, this has to be considered in
the differential diagnosis of nodal disease in patients with a history of breast
cancer. Here, we report the case of a 73-year-old female with a past medical
history of breast cancer, presenting with an ipsilateral axillary metastatic
carcinoma. The immunohistochemical profile of the metastatic lesion was
consistent with a high grade serous carcinoma. After undergoing a total abdominal
hysterectomy and salpingo-oophorectomy, thorough pathological examination
revealed two microscopic foci of serous carcinoma in the right fallopian tube,
not detectable by preoperative magnetic resonance imaging. In this context, the
poorly differentiated appearance of the metastatic tumor and positive staining
for estrogen receptor, might lead to a misdiagnosis of metastatic breast
carcinoma. As the therapeutic implications differ, it is important for the
pathologist to critically assess axillary lymph node metastases, even in patients
with a past history of ipsilateral breast carcinoma and no other known primary
tumors.
PMID- 25110593
TI - Adult hippocampal neurogenesis in Parkinson's disease: impact on neuronal
survival and plasticity.
AB - In Parkinson's disease (PD) and other synucleinopathies, chronic
neurodegeneration occurs within different areas of the central nervous system
leading to progressive motor and nonmotor symptoms. The symptomatic treatment
options that are currently available do not slow or halt disease progression.
This highlights the need of a better understanding of disease mechanisms and
disease models. The generation of newborn neurons in the adult hippocampus and in
the subventricular zone/olfactory bulb system is affected by many different
regulators and possibly involved in memory processing, depression, and olfaction,
symptoms which commonly occur in PD. The pathology of the adult neurogenic niches
in human PD patients is still mostly elusive, but different preclinical models
have shown profound alterations of adult neurogenesis. Alterations in stem cell
proliferation, differentiation, and survival as well as neurite outgrowth and
spine formation have been related to different aspects in PD pathogenesis.
Therefore, neurogenesis in the adult brain provides an ideal model to study
disease mechanisms and compounds. In addition, adult newborn neurons have been
proposed as a source of endogenous repair. Herein, we review current knowledge
about the adult neurogenic niches in PD and highlight areas of future research.
PMID- 25110597
TI - Nodular Lymphocyte Predominant Hodgkin Lymphoma versus T-Cell/Histiocyte-Rich
Large B-Cell Lymphoma: A Diagnostic Challenge.
AB - Lymphomas with overlapping histological features of two distinct entities cause
difficulty in classification. Their classification is of particular significance
when the two alternatives require different treatment modalities. We present a
diagnostically challenging case of a nodular lymphocyte predominant Hodgkin
lymphoma (NLPHL) with features of T-cell/histiocyte-rich large B-cell lymphoma
(THRLBCL). Our patient is a 39-year-old woman who presented with painless
subclavicular and axillary lymphadenopathy. The biopsied lymph node showed
diffuse architectural effacement and scattered large neoplastic cells with large
irregular nuclei and prominent nucleoli. These cells were positive for CD20 and
Bcl-6 and negative for CD15, CD30, IgD, and Bcl-2. The background cells were
predominantly T lymphocytes, whereas B cells were markedly depleted. The lymph
node was interpreted as NLPHL, consistent with THRLBCL-like variant. NLPHL,
especially THRLBC-like variant, and de novo THRLBCL are characterized by
significant morphologic and immunophenotypic overlap. Our case demonstrates a
rare predominance of background T-cells in NLPHL and emphasizes the importance of
thorough evaluation of multiple morphologic and immunophenotypic features as an
essential approach for arriving at the correct diagnosis.
PMID- 25110598
TI - Sarcoidosis incidentally diagnosed: a case report.
AB - Sarcoidosis is a chronic, granulomatous condition with unknown cause. Because
most of the patients are free of clinical symptoms, sarcoidosis should be
considered in differential diagnosis if noncaseous granuloma is noted in
biopsies, performed for other reasons. With no clinical symptoms, our patient was
diagnosed with sarcoidosis upon identifying noncaseous granuloma in the lymph
node biopsy material collected during the laparoscopic operation, performed for
gallbladder polyp.
PMID- 25110599
TI - Rapidly destructive inflammatory arthritis of the hip.
AB - Rapidly destructive coxarthrosis (RDC) is a rare syndrome that involves
aggressive hip joint destruction within 6-12 months of symptom onset with no
single diagnostic laboratory, pathological, or radiographic finding. We report an
original case of RDC as an initial presentation of seronegative rheumatoid
arthritis (RA) in a 57-year-old Caucasian woman presenting with 6 months of
progressive right groin pain and no preceding trauma or chronic steroid use. Over
5 months, she was unable to ambulate and plain films showed complete resorption
of the right femoral head and erosion of the acetabulum. There were inflammatory
features seen on computed tomography (CT) and magnetic resonance imaging (MRI).
She required a right total hip arthroplasty, but arthritis in other joints showed
improvement with triple disease modifying antirheumatic drugs (DMARD) therapy and
almost complete remission with the addition of adalimumab. We contrast our case
of RDC as an initial presentation of RA to 8 RDC case reports of patients with
established RA. Furthermore, this case highlights the importance of obtaining
serial imaging to evaluate a patient with persistent hip symptoms and rapid
functional deterioration.
PMID- 25110600
TI - Treatment resistant severe digital ischemia associated with antiphospholipid
syndrome in a male patient with systemic sclerosis.
AB - We report the case of a male patient with limited cutaneous systemic sclerosis
(SSc) that was complicated with severe digital ischemia, resistant to medical
treatment. Due to the lack of treatment response, further laboratory and imaging
studies were conducted. Findings were compatible with antiphospholipid syndrome
and oral warfarin was added to the treatment regimen. After successful
anticoagulation no further recurrences of digital ischemia were seen. An
underlying etiology in SSc patients with treatment resistant digital ischemic
necrosis should be suspected for accompanying antiphospholipid syndrome (APS).
PMID- 25110601
TI - Laparoscopic Right Hemicolectomy in an Automated Peritoneal Dialysis Patient
without Removal of the PD Catheter: A Case Report.
AB - Introduction. Laparotomy in patients on peritoneal dialysis (PD) is associated
with an increased risk of morbidity. Furthermore, standard protocol recommends
removal of the PD catheter when surgery on the intestine is required. As far as
we are aware, this is the first case report of laparoscopic right hemicolectomy
in a patient on automated PD where the PD catheter was left in situ. Case Report.
A 61-year-old man man on APD who presented with a caecal carcinoma was stabilised
on temporary haemodialysis (HD) prior to undergoing a laparoscopic right
hemicolectomy without removal of the PD catheter. He made an uneventful recovery
and APD was resumed successfully 2 weeks after surgery. Discussion. PD patients
undergoing intra-abdominal surgery are at increased risk of complications. While
the benefits of laparoscopic surgery in the standard surgical population are well
established, there is limited experience of the technique in PD patients.
Possible advantages could theoretically be early resumption of PD as well as less
PD failure due to the formation of adhesions. Conclusion. Our experience with
this case indicates that laparoscopic right hemicolectomy in a background of PD
can be undertaken without removal of the PD catheter and is associated with early
resumption of PD.
PMID- 25110602
TI - Incidental Phaeochromocytoma on Staging PET-CT in a Patient with a Sigmoid Tumour
and Situs Inversalis Totalis.
AB - An adrenal "incidentaloma" is defined as an unexpected finding on radiological
imaging performed for unrelated indications. Improvements in radiological
technology have seen a dramatic increase in this phenomenon. We report the unique
case of a 60-year-old female presenting with a 6-month history of abdominal pain,
altered bowel habit, and rectal bleeding. Her past medical history included situs
inversus totalis and a patent ductus arteriosus. Colonoscopy revealed an
ulcerated tumour in her sigmoid colon. Staging PET-CT confirmed a sigmoid tumour
and also identified a large heterogenous enhancing FDG-avid right adrenal mass.
Biochemical testing/MIBG imaging confirmed a right adrenal phaeochromocytoma.
Hypertension was controlled and excision was performed via a transperitoneal
laparoscopic adrenalectomy, in the left lateral decubitus position. Uniquely,
liver retraction was not required due to its position in the left hypochondrium.
Histology confirmed a benign 46 mm phaeochromocytoma. Subsequent uncomplicated
sigmoid colectomy/right salpingo-oophorectomy for a locally advanced colonic
tumour was performed with adjuvant chemotherapy. This case highlights the
importance of accurately identifying functioning adrenal tumours before elective
surgery as undiagnosed phaeochromocytomas carry significant intraoperative
morbidity/mortality. Right adrenalectomy was made easier in this patient by the
liver's unique position. Uncomplicated colorectal resection was made possible by
combined preoperative functional/anatomical imaging.
PMID- 25110603
TI - Recurrent volvulus of an ileal pouch requiring repeat pouchopexy: a lesson
learnt.
AB - Introduction. Restorative surgery for ulcerative colitis with ileal pouch anal
anastomosis (IPAA) is frequently accompanied by complications. Volvulus of the
ileal pouch is one of the most rarely reported late complications and to our
knowledge no report exists on reoperative surgery for this condition. Case
Report. A 58-year-old woman who previously had undergone restorative
proctocolectomy due to ulcerative colitis with an IPAA presented with volvulus of
the pouch. She was operated with a single row pouchopexy to the presacral fascia.
Two months later she returned with a recurrent volvulus. At reoperation, the
pouch was found to have become completely detached from the fascia. A new pexy
was made by firmly anchoring the pouch with two rows of sutures to the presacral
fascia as well as with sutures to the lateral pelvic walls. At follow-up after
five months she was free of symptoms. Conclusion. This first report ever on
reoperative surgery for volvulus of a pelvic pouch indicates that a single row
pouchopexy might be insufficient for preventing retwisting. Several rows seem to
be needed.
PMID- 25110604
TI - Laparoscopic-assisted resection of jejunojejunal intussusception caused by a
juvenile polyp in an adult.
AB - Most bowel intussusceptions in adults have a leading point. However, there have
been few reports of jejunojejunal intussusception secondary to a solitary
juvenile polyp in adult. We report herein the case of a 19-year-old female with a
solitary juvenile polyp in the jejunum causing intussusception. Laparoscopic
assisted reduction and segmental resection of the jejunum were successfully done
for the patient.
PMID- 25110605
TI - Successful management of repetitive urinary obstruction and anuria caused by
double j stent calculi formation after renal transplantation.
AB - This report firstly describes an extremely rare case of repetitive double J stent
calculi formation after renal transplantation caused by the
antihyperparathyroidism (HPT) drug calcitriol. In 2012, a woman initially
presented to our hospital for anuria with lower abdominal pain. She was diagnosed
with allograft hydronephrosis and double J stents obstruction by calculi
formation after transplantation and treated with triplicate stents replacements
in another hospital without clinical manifestations improvements. Through
detailed exploration of medical history, we conclude that the abnormal calculi
formation is due to the calcitriol (1,25-dihydroxyvitamin D3) administration, a
drug which can increase renal tubular reabsorption of calcium for treating
posttransplant HPT bone disease. After discontinuing calcitriol, the patient was
stone-free and had a good recovery without severe complications during the 9
month follow-up. Our novel findings may provide an important clue and approach to
managing formidable repetitive double J stent calculi formation in the clinical
trial.
PMID- 25110606
TI - Iatrogenic salt water drowning and the hazards of a high central venous pressure.
AB - Current teaching and guidelines suggest that aggressive fluid resuscitation is
the best initial approach to the patient with hemodynamic instability. The source
of this wisdom is difficult to discern, however, Early Goal Directed therapy
(EGDT) as championed by Rivers et al. and the Surviving Sepsis Campaign
Guidelines appears to have established this as the irrefutable truth. However,
over the last decade it has become clear that aggressive fluid resuscitation
leading to fluid overload is associated with increased morbidity and mortality
across a diverse group of patients, including patients with severe sepsis as well
as elective surgical and trauma patients and those with pancreatitis. Excessive
fluid administration results in increased interstitial fluid in vital organs
leading to impaired renal, hepatic and cardiac function. Increased extra-vascular
lung water (EVLW) is particularly lethal, leading to iatrogenic salt water
drowning. EGDT and the Surviving Sepsis Campaign Guidelines recommend targeting a
central venous pressure (CVP) > 8 mmHg. A CVP > 8 mmHg has been demonstrated to
decrease microcirculatory flow, as well as renal blood flow and is associated
with an increased risk of renal failure and death. Normal saline (0.9% salt
solution) as compared to balanced electrolyte solutions is associated with a
greater risk of acute kidney injury and death. This paper reviews the adverse
effects of large volume resuscitation, a high CVP and the excessive use of normal
saline.
PMID- 25110607
TI - Managing sarcopenia and its related-fractures to improve quality of life in
geriatric populations.
AB - Sarcopenia, an aging-induced generalized decrease in muscle mass, strength, and
function, is known to affect elderly individuals by decreasing mobile function
and increasing frailty and imbalance that lead to falls and fragile fractures.
Sarcopenia is a known risk factor for osteoporotic fractures, infections, and
early death in some specific situations. The number of patients with sarcopenia
is estimated to increase to 500 million people in the year 2050. Sarcopenia is
believed to be caused by multiple factors such as disuse, malnutrition, age
related cellular changes, apoptosis, and genetic predisposition; however, this
remains to be determined. Various methods have been developed, but no safe or
effective treatment has been found to date. This paper is a review on the
association between sarcopenia and its related-fractures and their diagnoses and
management methods to prevent fractures.
PMID- 25110609
TI - Accelerated aging in schizophrenia patients: the potential role of oxidative
stress.
AB - Several lines of evidence suggest that schizophrenia, a severe mental illness
characterized by delusions, hallucinations and thought disorder is associated
with accelerated aging. The free radical (oxidative stress) theory of aging
assumes that aging occurs as a result of damage to cell constituents and
connective tissues by free radicals arising from oxygen-associated reactions.
Schizophrenia has been associated with oxidative stress and chronic inflammation,
both of which also appear to reciprocally induce each other in a positive
feedback manner. The buildup of damaged macromolecules due to increased oxidative
stress and failure of protein repair and maintenance systems is an indicator of
aging both at the cellular and organismal level. When compared with age-matched
healthy controls, schizophrenia patients have higher levels of markers of
oxidative cellular damage such as protein carbonyls, products of lipid
peroxidation and DNA hydroxylation. Potential confounders such as antipsychotic
medication, smoking, socio-economic status and unhealthy lifestyle make it
impossible to solely attribute the earlier onset of aging-related changes or
oxidative stress to having a diagnosis of schizophrenia. Regardless of whether
oxidative stress can be attributed solely to a diagnosis of schizophrenia or
whether it is due to other factors associated with schizophrenia, the available
evidence is in support of increased oxidative stress-induced cellular damage of
macromolecules which may play a role in the phenomenon of accelerated aging
presumed to be associated with schizophrenia.
PMID- 25110610
TI - mTOR Signaling from Cellular Senescence to Organismal Aging.
AB - The TOR (target of rapamycin) pathway has been convincingly shown to promote
aging in various model organisms. In mice, inhibiting mTOR (mammalian TOR) by
rapamycin treatment later in life can significantly extend lifespan and mitigate
multiple age-related diseases. However, the underlying mechanisms are poorly
understood. Cellular senescence is strongly correlated to organismal aging
therefore providing an attractive model to examine the mechanisms by which mTOR
inhibition contributes to longevity and delaying the onset of related diseases.
In this review, we examine the connections between mTOR and cellular senescence
and discuss how understanding cellular senescence on the aspect of mTOR signaling
may help to fully appreciate its role in the organismal aging. We also highlight
the opposing roles of senescence in various human diseases and discuss the
caveats in interpreting the emerging experimental data.
PMID- 25110611
TI - Effects of living at higher altitudes on mortality: a narrative review.
AB - Beside genetic and life-style characteristics environmental factors may
profoundly influence mortality and life expectancy. The high altitude climate
comprises a set of conditions bearing the potential of modifying morbidity and
mortality of approximately 400 million people who are permanently residing at
elevations above 1500 meters. However, epidemiological data on the effects of
high altitude living on mortality from major diseases are inconsistent probably
due to differences in ethnicity, behavioral factors and the complex interactions
with environmental conditions. The available data indicate that residency at
higher altitudes are associated with lower mortality from cardiovascular
diseases, stroke and certain types of cancer. In contrast mortality from COPD and
probably also from lower respiratory tract infections is rather elevated. It may
be argued that moderate altitudes are more protective than high or even very high
altitudes. Whereas living at higher elevations may frequently protect from
development of diseases, it could adversely affect mortality when diseases
progress. Corroborating and expanding these findings would be helpful for
optimization of medical care and disease management in the aging residents of
higher altitudes.
PMID- 25110608
TI - Metabolic disturbances in diseases with neurological involvement.
AB - Degeneration of specific neuronal populations and progressive nervous system
dysfunction characterize neurodegenerative diseases, including Alzheimer's
disease and Parkinson's disease. These findings are also reported in inherited
diseases such as phenylketonuria and glutaric aciduria type I. The involvement of
mitochondrial dysfunction in these diseases was reported, elicited by genetic
alterations, exogenous toxins or buildup of toxic metabolites. In this review we
shall discuss some metabolic alterations related to the pathophysiology of
diseases with neurological involvement and aging process. These findings may help
identifying early disease biomarkers and lead to more effective therapies to
improve the quality of life of the patients affected by these devastating
illnesses.
PMID- 25110612
TI - Nothobranchius as a model for aging studies. A review.
AB - In recent decades, the increase in human longevity has made it increasingly
important to expand our knowledge on aging. To accomplish this, the use of animal
models is essential, with the most common being mouse (phylogenetically similar
to humans, and a model with a long life expectancy) and Caenorhabditis elegans
(an invertebrate with a short life span, but quite removed from us in
evolutionary terms). However, some sort of model is needed to bridge the
differences between those mentioned above, achieving a balance between
phylogenetic distance and life span. Fish of the genus Nothobranchius were
suggested 10 years ago as a possible alternative for the study of the aging
process. In the meantime, numerous studies have been conducted at different
levels: behavioral (including the study of the rest-activity rhythm),
populational, histochemical, biochemical and genetic, among others, with very
positive results. This review compiles what we know about Nothobranchius to date,
and examines its future prospects as a true alternative to the classic models for
studies on aging.
PMID- 25110613
TI - Estimation of Heterogeneity in Diagnostic Parameters of Age-related Diseases.
AB - The heterogeneity of parameters is a ubiquitous biological phenomenon, with
critical implications for biological systems functioning in normal and diseased
states. We developed a method to estimate the level of objects set heterogeneity
with reference to particular parameters and applied it to type II diabetes and
heart disease, as examples of age-related systemic dysfunctions. The Friedman
test was used to establish the existence of heterogeneity. The Newman-Keuls
multiple comparison method was used to determine clusters. The normalized Shannon
entropy was used to provide the quantitative evaluation of heterogeneity. There
was obtained an estimate for the heterogeneity of the diagnostic parameters in
healthy subjects, as well as in heart disease and type II diabetes patients,
which was strongly related to their age. With aging, as with the diseases, the
level of heterogeneity (entropy) was reduced, indicating a formal analogy between
these phenomena. The similarity of the patterns in aging and disease suggested a
kind of "early aging" of the diseased subjects, or alternatively a "disease-like"
aging process, with reference to these particular parameters. The proposed method
and its validation on the chronic age-related disease samples may support a way
toward a formal mathematical relation between aging and chronic diseases and a
formal definition of aging and disease, as determined by particular heterogeneity
(entropy) changes.
PMID- 25110614
TI - Beyond IC50s: Towards Robust Statistical Methods for in vitro Association
Studies.
AB - Cell line cytotoxicity assays have become increasingly popular approaches for
genetic and genomic studies of differential cytotoxic response. There are an
increasing number of success stories, but relatively little evaluation of the
statistical approaches used in such studies. In the vast majority of these
studies, concentration response is summarized using curve-fitting approaches, and
then summary measure(s) are used as the phenotype in subsequent genetic
association studies. The curve is usually summarized by a single parameter such
as the curve's inflection point (e.g. the EC/IC50). Such modeling makes major
assumptions and has statistical limitations that should be considered. In the
current review, we discuss the limitations of the EC/IC50 as a phenotype in
association studies, and highlight some potential limitations with a simulation
experiment. Finally, we discuss some alternative analysis approaches that have
been shown to be more robust.
PMID- 25110616
TI - Creating a safe space to learn: The significant role of graduate students in
fostering educational engagement and aspirations among urban youth.
PMID- 25110615
TI - Vitamin C Transporters, Recycling and the Bystander Effect in the Nervous System:
SVCT2 versus Gluts.
AB - Vitamin C is an essential micronutrient in the human diet; its deficiency leads
to a number of symptoms and ultimately death. After entry into cells within the
central nervous system (CNS) through sodium vitamin C transporters (SVCTs) and
facilitative glucose transporters (GLUTs), vitamin C functions as a
neuromodulator, enzymatic cofactor, and reactive oxygen species (ROS) scavenger;
it also stimulates differentiation. In this review, we will compare the molecular
and structural aspects of vitamin C and glucose transporters and their expression
in endothelial or choroid plexus cells, which form part of the blood-brain
barrier and blood-cerebrospinal fluid (CSF) barrier, respectively. Additionally,
we will describe SVCT and GLUT expression in different cells of the brain as well
as SVCT2 distribution in tanycytes and astrocytes of the hypothalamic region.
Finally, we will describe vitamin C recycling in the brain, which is mediated by
a metabolic interaction between astrocytes and neurons, and the role of the
"bystander effect" in the recycling mechanism of vitamin C in both normal and
pathological conditions.
PMID- 25110618
TI - Tuberculous meningitis: Diagnostic and therapeutic challenges.
AB - Neurologists are often the first medical providers to evaluate patients with
possible infectious meningitis. Knowledge of the clinical presentations and
cerebrospinal fluid, microbiologic, and neuroimaging findings for different
etiologies is essential to make a prompt diagnosis and initiate appropriate
treatment. Tuberculosis is a common cause of meningitis in developing countries
with a high prevalence of pulmonary tuberculosis. However, tuberculosis affects
populations in every country and all neurologists need to be vigilant for
possible cases of tuberculous meningitis presenting to their medical facilities.
This article discusses the challenges of diagnosing and treating tuberculous
meningitis and highlights recent advances in diagnostic technology.
PMID- 25110617
TI - Fertility Preservation for Prepubertal Girls: Update and Current Challenges.
AB - With increasing rates of diagnosis of childhood cancers and the evolution of more
effective treatment options resulting in prolonged life spans, fertility
preservation counseling is an integral component of the discussion at the time of
diagnosis of childhood cancers. The primary fertility preservation option that
exists for prepubertal girls is ovarian tissue cryopreservation. Although ovarian
tissue cryopreservation is still considered to be experimental in nature, live
births have resulted from orthotopic tissue transplantation. Fertility
preservation should be offered to all prepubertal girls at high-risk for
premature ovarian failure as a result of gonadotoxic treatment. Ethical and legal
questions surrounding these issues must be considered as more and more pediatric
patients pursue fertility preservation.
PMID- 25110619
TI - Diagnosis and management of acute encephalitis: A practical approach.
AB - Encephalitis results in considerable morbidity and mortality in the United States
and worldwide. Neurologists are often consulted or directly care for patients
with encephalitis admitted to the hospital and must be able to discriminate
between encephalitis and the many conditions that mimic it. Moreover,
neurologists must be familiar with the myriad causes of encephalitis in order to
develop a practical approach to diagnostic testing and treatment. An
understanding of recent advances in management, particularly with respect to
autoimmune etiologies and critical care approaches, is equally important. Here,
we summarize a general approach to the care of adult patients with encephalitis.
PMID- 25110620
TI - Dementia in MS complicated by coexistent Alzheimer disease: Diagnosis premortem
and postmortem.
AB - Distinguishing dementia due to multiple sclerosis (MS) from that of an
accompanying neurodegenerative dementia coexisting with MS has been difficult.
The recent introduction of Alzheimer disease (AD) biomarkers of amyloid-beta and
neuronal degeneration has improved diagnosis of AD premortem. We describe 3
patients with MS with coexisting AD, 1 diagnosed at autopsy before AD biomarkers
were available and 2 diagnosed premortem by decreased CSF amyloid-beta1-42/tau
index, MRI, and 18F-flourodeoxyglucose-PET patterns. AD biomarkers may be of
diagnostic value in selected patients with severe dementia and MS.
PMID- 25110621
TI - Neurology goes global: Opportunities in international health.
AB - In recent years, the need for additional neurologists and neurologic expertise in
many low- and middle-income countries (LMIC) has become more apparent. Many
organizations are committed to this unmet need, but the scope of the problem
remains mostly underappreciated. Neurologists may be skeptical about their value
in resource-limited settings, yet we are critically needed and can have a marked
effect. International experiences, however, must be carried out in ethical,
informed, and sustainable ways in tandem with local health care providers when
possible. We present a brief overview of critical issues in global neurology, the
importance of focusing on benefits to the LMIC, and options for volunteer
opportunities in clinical service, education, research, and disaster relief.
Finally, we offer practical pointers and resources for planning these
experiences.
PMID- 25110622
TI - State neurologic societies and the AAN: Strengthening neurology for the future.
AB - This report considers the recommendations of the State Society Task Force (SSTF),
which evaluated how the relationship between the American Academy of Neurology
(AAN) and neurologic societies of individual states can foster the care of
patients with neurologic diseases. The task force also evaluated the role of
state neurosociety and state medical society interactions in supporting the
profession of neurology. The SSTF recommended that the AAN expand current support
services to state neurosocieties and foster additional neurosociety development.
Specific services to be considered by the AAN include online combined AAN/state
neurosociety dues payment and enhanced Web support. The role of the AAN as a
liaison between state neurosocieties and state medical societies is important to
facilitate state level advocacy for neurology.
PMID- 25110623
TI - Acute HIV infection presenting as fulminant meningoencephalitis with massive CSF
viral replication.
AB - A 22-year-old man presented to the emergency department with 10 days of malaise,
generalized rash, sore throat, oral ulcers, headache, nausea, and vomiting. On
examination he had fever (101.5 degrees F), hepatosplenomegaly, generalized
maculopapular rash, and lymphadenopathy. He rapidly became obtunded, requiring
intubation. Initial laboratory studies showed mild transaminitis, increased
lactate dehydrogenase, and 4,600 leukocytes per MUL with 61% bands and 18%
lymphocytes. Bacterial and fungal blood cultures were negative as well as a rapid
HIV test, additional serologies (including rapid plasma reagin and Treponema
pallidum particle agglutination), quantitative PCRs (for viruses other than HIV),
and urine and blood toxicology. CSF, on hospital day 4, showed a lymphocytic
pleocytosis (total leukocytes: 100), high protein, borderline hypoglycorrhachia,
and negative Gram stain and culture. Brain MRI revealed no meningeal enhancement
or masses. EEG revealed no epileptiform activity. Flow cytometry on bone marrow
biopsy and CSF found no evidence of malignancy; neither did an excisional lymph
node biopsy (figure 1). An immunofluorescent assay test for HIV returned
inconclusive and a Western blot detected HIV gp120/gp160 bands. Quantitative HIV
RNA PCR was 1.4 * 106 copies/mL in plasma and in CSF exceeded the upper limit of
quantitation (107 copies/mL) (figure 2).
PMID- 25110624
TI - Applications of Brain-Machine Interface Systems in Stroke Recovery and
Rehabilitation.
AB - Stroke is a leading cause of disability, significantly impacting the quality of
life (QOL) in survivors, and rehabilitation remains the mainstay of treatment in
these patients. Recent engineering and technological advances such as brain
machine interfaces (BMI) and robotic rehabilitative devices are promising to
enhance stroke neu-rorehabilitation, to accelerate functional recovery and
improve QOL. This review discusses the recent applications of BMI and robotic
assisted rehabilitation in stroke patients. We present the framework for
integrated BMI and robotic-assisted therapies, and discuss their potential
therapeutic, assistive and diagnostic functions in stroke rehabilitation.
Finally, we conclude with an outlook on the potential challenges and future
directions of these neurotechnologies, and their impact on clinical
rehabilitation.
PMID- 25110625
TI - The Immune System and AMD.
AB - Age related macular degeneration (AMD) is a complex, multifactorial disease that
has yet to be completely understood. Significant efforts in the basic and
clinical sciences have unveiled numerous areas which appear to be critical in the
pathogenesis of this disease. The alternative complement pathway, immune cell
activation, and autoimmunity are all emerging as important themes to the
suspected immunologic origins of this disease. Advancement toward a complete
understanding of these processes is important in development of new techniques
for disease monitoring and treatment.
PMID- 25110626
TI - Habitual exercise plus dietary supplementation with milk fat globule membrane
improves muscle function deficits via neuromuscular development in senescence
accelerated mice.
AB - We examined the effects of habitual exercise plus nutritional intervention
through consumption of milk fat globule membrane (MFGM), a milk component, on
aging-related deficits in muscle mass and function in senescence-accelerated P1
mice. Combining wheel-running and MFGM (MFGMEx) intake significantly attenuated
age-related declines in quadriceps muscle mass (control: 318 +/- 6 mg; MFGMEx:
356 +/- 9 mg; P < 0.05) and in contractile force (1.4-fold and 1.5-fold higher in
the soleus and extensor digitorum longus muscles, respectively). Microarray
analysis of genes in the quadriceps muscle revealed that MFGMEx stimulated
neuromuscular development; this was supported by significantly increased docking
protein-7 (Dok-7) and myogenin mRNA expression. Treatment of differentiating
myoblasts with MFGM-derived phospholipid or sphingolipid fractions plus
mechanical stretching also significantly increased Dok-7 mRNA expression. These
findings suggest that habitual exercise plus dietary MFGM improves muscle
function deficits through neuromuscular development, and that phospholipid and
sphingolipid in MFGM contribute to its physiological actions.
PMID- 25110627
TI - Effects of a pre-and post-workout protein-carbohydrate supplement in trained
crossfit individuals.
AB - PURPOSE: The purpose was to assess effects of a pre- and a post-workout protein
carbohydrate supplement on CrossFit-specific performance and body composition.
METHODS: In an open label randomized study, 13 male and 16 female trained
Crossfit participants (mean +/- SD; age: 31.87 +/- 7.61 yrs, weight: 78.68 +/-
16.45 kg, percent body fat: 21.97 +/- 9.02) were assessed at 0 and 6 weeks for
body composition, VO2max, Wingate peak (WPP) and mean power (WMP), in addition to
sport-specific workouts (WOD1: 500 m row, 40 wall balls, 30 push-ups, 20 box
jumps, 10 thrusters for time; WOD2: 15 minutes to complete an 800 m run "buy in",
followed by as many rounds as possible (AMRAP) of 5 burpees, 10 Kettlebell
swings, 15 air squats). The supplement (SUP) group consisted of 19 g of a pre
workout drink (extracts of pomegranate, tart cherry, green and black tea) taken
30 minutes before and a post-workout protein (females: 20 g; males: 40 g) and
carbohydrate (females: 40 g; males: 80 g) supplement consumed immediately after
each workout. The control (CTL) group consumed only water one hour before or
after workouts. Participants completed three (minimum) varied workouts per week
at a CrossFit gym as typical to habitual training throughout the six week study.
Data were analyzed by repeated measures ANOVA (p <0 .05), 95% Confidence
Intervals, and Magnitude Inferences. RESULTS: There were no time * group
interactions for body composition, WMP, or WOD1 based on ANOVA statistics.
VO2MAX, WPP, and WOD2 results revealed that the pre/post supplements were likely
beneficial after 95% Confidence Intervals and Magnitude Inferences analysis.
CONCLUSION: The combination of proprietary supplements taken for 6 weeks may
provide benefits during certain sport-specific performance in trained CrossFit
athletes but not others.
PMID- 25110628
TI - Approaches for the design of reduced toxicant emission cigarettes.
AB - Cigarette smoking causes serious diseases through frequent and prolonged exposure
to toxicants. Technologies are being developed to reduce smokers' toxicant
exposure, including filter adsorbents, tobacco treatments and substitutes. This
study examined the effect of modifications to filter ventilation, variations in
cigarette circumference and active charcoal filter length and loading, as well as
combinations of these features in a reduced-toxicant prototype (RTP) cigarette,
on the yields of toxicants in cigarette smoke. An air-dilution mechanism, called
split-tipping, was developed in which a band of porous paper in the centre of the
filter tipping functions to minimise the loss of effective filter ventilation
that occurs at the high flow rates encountered during human-smoking, and to
facilitate the diffusional loss of volatile toxicants. As compared with
conventional filter ventilation cigarettes, split-tipping reduced tar and
volatile smoke constituent emissions under high flow rate machine-smoking
conditions, most notably for products with a 1-mg ISO tar yield. Furthermore,
mouth level exposure (MLE) to tar and nicotine was reduced among smokers of 1-mg
ISO tar cigarettes in comparison to smokers of cigarettes with traditional filter
ventilation. For higher ISO tar level cigarettes, however, there were no
significant reductions in MLE. Smaller cigarette circumferences reduced
sidestream toxicant yields and modified the balance of mainstream smoke chemistry
with reduced levels of aromatic amines and benzo[a]pyrene but increased yields of
formaldehyde. Smaller circumference cigarettes also had lower mainstream yields
of volatile toxicants. Longer cigarette filters containing increased levels of
high-activity carbon (HAC) showed reduced machine-smoking yields of volatile
toxicants: with up to 97% removal for some volatile toxicants at higher HAC
loadings. Split-tipping was combined with optimal filter length and cigarette
circumference in an RTP cigarette that gave significantly lower mainstream (up to
~90%) and sidestream (predominately 20%-60%) smoke yields of numerous toxicants
as compared with a commercial comparator cigarette under machine-smoking
conditions. Significantly lower mainstream and sidestream smoke toxicant yields
were observed for an RTP cigarette comprising several toxicant reducing
technologies; these observations warrant further evaluation in clinical studies
where real-world relevance can be tested using biomarkers of exposure and
physiological effect.
PMID- 25110629
TI - Pigeonpea genotypes influence parasitization preference and survival and
development of the Helicoverpa armigera larval parasitoid, Campoletis chlorideae.
AB - Studies were undertaken to identify pigeonpea, Cajanus cajan (L.) Millspaugh and
the wild relative of pigeonpea, Cajanus scarabaeoides (L.) (accession ICPW 125,)
genotypes that are hospitable to the pod borer, Helicoverpa armigera (Hubner)
(Lepidoptera: Noctuidae) larval parasitoid, Campoletis chlorideae Uchida
(Hymenoptera: Ichneumonidae) for the management of this pest in pigeonpea based
cropping systems. Percentage parasitization of the H. armigera larvae by the C.
chlorideae females was greater under no-choice conditions than under multi-choice
conditions because of forced parasitization under no-choice conditions. Lowest
parasitization was recorded on the wild relative, ICPW 125, which may be due to
long nonglandular hairs and low survival of H. armigera larvae. Parasitization of
H. armigera larvae was greater under no-choice, dual-choice and/or multi-choice
conditions on ICPL 87, ICPL 87119 and ICPL 87091, which are susceptible to H.
armigera, than on the pod borer-resistant genotypes ICPL 332WR, ICPL 84060 and
ICPB 2042; while survival and development of the parasitoid was better on H.
armigera larvae fed on ICPL 87, ICPL 87119, LRG 41, ICP 7035 and ICPL 87091 than
on ICPL 332WR, ICPL 84060, ICPB 2042 and ICPW 125. The genotypes ICPL 87, ICPL
87119, LRG 42 and ICPL 87091 that are hospitable to C. chloridae, are better
suited for use in integrated pest management to minimize the losses due to H.
armigera in pigeonpea.
PMID- 25110630
TI - Isolation and enzyme bioprospection of endophytic bacteria associated with plants
of Brazilian mangrove ecosystem.
AB - The mangrove ecosystem is a coastal tropical biome located in the transition zone
between land and sea that is characterized by periodic flooding, which confers
unique and specific environmental conditions on this biome. In these ecosystems,
the vegetation is dominated by a particular group of plant species that provide a
unique environment harboring diverse groups of microorganisms, including the
endophytic microorganisms that are the focus of this study. Because of their
intimate association with plants, endophytic microorganisms could be explored for
biotechnologically significant products, such as enzymes, proteins, antibiotics
and others. Here, we isolated endophytic microorganisms from two mangrove
species, Rhizophora mangle and Avicennia nitida, that are found in streams in two
mangrove systems in Bertioga and Cananeia, Brazil. Bacillus was the most
frequently isolated genus, comprising 42% of the species isolated from Cananeia
and 28% of the species from Bertioga. However, other common endophytic genera
such as Pantoea, Curtobacterium and Enterobacter were also found. After
identifying the isolates, the bacterial communities were evaluated for enzyme
production. Protease activity was observed in 75% of the isolates, while
endoglucanase activity occurred in 62% of the isolates. Bacillus showed the
highest activity rates for amylase and esterase and endoglucanase. To our
knowledge, this is the first reported diversity analysis performed on endophytic
bacteria obtained from the branches of mangrove trees and the first overview of
the specific enzymes produced by different bacterial genera. This work
contributes to our knowledge of the microorganisms and enzymes present in
mangrove ecosystems.
PMID- 25110631
TI - Different pioneer plant species select specific rhizosphere bacterial communities
in a high mountain environment.
AB - The rhizobacterial communities of 29 pioneer plants belonging to 12 species were
investigated in an alpine ecosystem to assess if plants from different species
could select for specific rhizobacterial communities. Rhizospheres and
unvegetated soils were collected from a floristic pioneer stage plot at 2,400 m
a.s.l. in the forefield of Weisskugel Glacier (Matsch Valley, South Tyrol,
Italy), after 160 years of glacier retreat. To allow for a culture-independent
perspective, total environmental DNA was extracted from both rhizosphere and bare
soil samples and analyzed by Automated Ribosomal Intergenic Spacer Analysis
(ARISA) and Denaturing Gradient Gel Electrophoresis (DGGE). ARISA fingerprinting
showed that rhizobacterial genetic structure was extremely different from bare
soil bacterial communities while rhizobacterial communities clustered strictly
together according to the plant species. Sequencing of DGGE bands showed that
rhizobacterial communities were mainly composed of Acidobacteria and
Proteobacteria whereas bare soil was colonized by Acidobacteria and Clostridia.
UniFrac significance calculated on DGGE results confirmed the rhizosphere effect
exerted by the 12 species and showed different bacterial communities (P < 0.05)
associated with all the plant species. These results pointed out that specific
rhizobacterial communities were selected by pioneer plants of different species
in a high mountain ecosystem characterized by oligotrophic and harsh
environmental conditions, during an early primary succession.
PMID- 25110632
TI - Immunogenicity of a monovalent 2009 influenza A (H1N1) vaccine in infants:
randomized, observer-masked, single-center clinical study.
AB - ABSTRACT: The aim of this study is to further investigate the immune response of
the inactivated split-virion vaccine for infants. We tested the immunogenicity
and safety of the inactivated split-virion vaccine in infants, aged 6-35 months,
for a randomized, observer-masked, age-stratified clinical study. We randomly
divided subjects into three groups: 7.5 MUg, 15 MUg of hemagglutinin antigen
dosage groups and seasonal influenza vaccine for children dosage group in a 2
dose regimen. A serologic analysis was performed at baseline and on day 21 and
42. 312 infants received a single dose injection of vaccine and 265 (84.94%)
infants received two doses injection of vaccine. Adverse reactions were mostly
mild or moderate. Among the subjects who received 7.5 MUg and 15 MUg of vaccine
for a single dose injection, the rate of hemagglutinin inhibition titer of 1:40
or greater were 52.48% (95% confidence interval (CI) 42.83 ~ 61.95) and 61.11%
(95% CI 50.78 ~ 70.53), respectively. Among the subjects receiving 7.5 MUg and 15
MUg of vaccine for two doses injection, the rate of hemagglutinin inhibition (HI)
titer of 1:40 or greater were 90.10% (95% CI 82.73 ~ 94.53) and 94.44% (95% CI
87.64 ~ 97.60), respectively. These data suggests that 15 MUg or 7.5 MUg dose of
hemagglutinin antigen of the inactivated split-virion vaccine was safe and two
doses of injection could induce a sufficient protective immune response in
infants. TRIAL REGISTRATION: CLINICAL TRIALS REGISTRATION: NCT01494740.
PMID- 25110633
TI - Shigella: A Highly Virulent and Elusive Pathogen.
AB - Despite a significant decrease in Shigella-related mortality, shigellosis
continues to carry a significant burden of disease worldwide, particularly in
Asia and Africa. Shigella is a highly virulent pathogen comprised of four major
species with numerous subtypes. Shigella dysenteriae and Shigella flexneri
infections are predominant in resource-limited settings. Clinical presentations
range from mild watery diarrhea to severe dysentery with systemic complications
such as electrolyte imbalance, seizures and hemolytic uremic syndrome. S.
dysenteriae subtype 1, the producer of Shiga toxin, causes the most severe
illness and highest mortality. Susceptible strains of Shigella may be effectively
treated with inexpensive oral antibiotics such as ampicillin or trimethoprim
sulfamethoxazole. Unfortunately, multidrug resistant strains have emerged that
have rendered most antibiotics, including fluoroquinolones and extended-spectrum
cephalosporins, ineffective. Management and prevention of shigellosis represents
a major public health challenge. The development of an effective vaccine is
urgently needed to decrease its global impact.
PMID- 25110634
TI - Weight Loss Programs May Have Beneficial or Adverse Effects on Fat Mass and
Insulin Sensitivity in Overweight and Obese Black Women.
AB - OBJECTIVE: Weight loss interventions have produced little change in insulin
sensitivity in black women, but mean data may obscure metabolic benefit to some
and adverse effects for others. Accordingly, we analyzed insulin sensitivity
relative to fat mass change following a weight loss program. DESIGN AND METHODS:
Fifty-four black women (BMI range 25.9 to 54.7 kg/m2) completed the 6-month
program that included nutrition information and worksite exercise facilities. Fat
mass was measured by dual-energy X-ray absorptiometry, and insulin sensitivity
index (SI) was calculated from an insulin-modified intravenous glucose tolerance
test using the minimal model. RESULTS: Baseline SI (range 0.74 to 7.58 l/mU-1*min
1) was inversely associated with fat mass (r = -0.516, p < 0.001), independent of
age. On average, subjects lost fat mass (baseline 40.8 +/- 12.4 to 39.4 +/- 12.6
kg [mean +/- SD], P < 0.01), but 17 women (32 %) actually gained fat mass. SI for
the group was unchanged (baseline 3.3 +/- 1.7 to 3.2 +/- 1.6, P = 0.67). However,
the tertile with greatest fat mass loss (-3.6 kg, range -10.7 to -1.7 kg)
improved insulin sensitivity (SI +0.3 +/- 1.2), whereas the tertile with net fat
mass gain (+0.9 kg, range -0.1 to +3.8 kg) had reduced insulin sensitivity (SI
0.7 +/- 1.3) from baseline values (P < 0.05 by ANOVA). CONCLUSIONS: Black women
in a weight loss program who lose fat mass may have improved insulin sensitivity,
but fat mass gain with diminished sensitivity is common. Additional support for
participants who fail to achieve fat mass loss early in an intervention may be
required for success.
PMID- 25110635
TI - Multidrug-resistant tuberculosis treatment with linezolid-containing regimen.
AB - The following is a case of multidrug-resistant pulmonary tuberculosis (MDR-TB)
that was treated successfully with a linezolid-containing regimen. It was found
that linezolid is an efficient medicine for MDR-TB treatment with an acceptable
side effect profile. Treatment was maintained for 18 months, and closely
monitoring toxicities did not reveal evidence of any neurologic adverse effects.
However, despite our expectation, thrombocytopenia was seen after 2 years follow
up.
PMID- 25110636
TI - Violent crime, suicide, and premature mortality in patients with schizophrenia
and related disorders: a 38-year total population study in Sweden.
AB - BACKGROUND: People with schizophrenia and related disorders are at an increased
risk of adverse outcomes, including conviction of a violent offence, suicide, and
premature mortality. However, the rates of, and risk factors for, these outcomes
need clarification as a basis for population-based and targeted interventions. We
aimed to determine rates and risk factors for these outcomes, and investigate to
what extent they are shared across outcomes and are specific to schizophrenia and
related disorders. METHODS: We undertook a total population cohort study in
Sweden of 24 297 patients with schizophrenia and related disorders between
January, 1972 and December, 2009. Patients were matched by age and sex to people
from the general population (n=485 940) and also to unaffected sibling controls
(n=26 357). First, we investigated rates of conviction of a violent offence,
suicide, and premature mortality, with follow-up until conviction of a violent
offence, emigration, death, or end of follow-up (Dec 31, 2009), whichever
occurred first. Second, we analysed associations between these adverse outcomes
and sociodemographic, individual, familial, and distal risk factors, for men and
women separately, with Cox proportional hazards models. Finally, we assessed time
trends in adverse outcomes between 1972 and 2009, for which we compared patients
with unaffected siblings, and analysed associations with changes in the number of
nights spent in inpatient beds in psychiatric facilities nationwide. FINDINGS:
Within 5 years of their initial diagnosis, 13.9% of men and 4.7% of women with
schizophrenia and related disorders had a major adverse outcome (10.7% of men and
2.7% of women were convicted of a violent offence, and 3.3% of men and 2.0% of
women died prematurely of any cause). During the study, the adjusted odds ratio
of any adverse outcomes for patients compared with general population controls
was 7.5 (95% CI 7.2-7.9) in men and 11.1 (10.2-12.1) in women. Three risk factors
that were present before diagnosis were predictive of any adverse outcome: drug
use disorders, criminality, and self-harm, which were also risk factors for these
outcomes in unaffected siblings and in the general population. Over the period
1973-2009, the odds of these outcomes increased in patients with schizophrenia
and related disorders compared with unaffected siblings. INTERPRETATION:
Schizophrenia and related disorders are associated with substantially increased
rates of violent crime, suicide, and premature mortality. Risk factors for these
three outcomes included both those specific to individuals with schizophrenia and
related disorders, and those shared with the general population. Therefore, a
combination of population-based and targeted strategies might be necessary to
reduce the substantial rates of adverse outcomes in patients with schizophrenia
and related disorders.
PMID- 25110637
TI - In vitro cytotoxicity of four calcium silicate-based endodontic cements on human
monocytes, a colorimetric MTT assay.
AB - OBJECTIVES: This study was performed to evaluate the cytotoxicity of four calcium
silicate-based endodontic cements at different storage times after mixing.
MATERIALS AND METHODS: Capillary tubes were filled with Biodentine (Septodont),
Calcium Enriched Mixture (CEM cement, BioniqueDent), Tech Biosealer Endo (Tech
Biosealer) and ProRoot MTA (Dentsply Tulsa Dental). Empty tubes and tubes
containing Dycal were used as negative and positive control groups respectively.
Filled capillary tubes were kept in 0.2 mL microtubes and incubated at 37C. Each
material was divided into 3 groups for testing at intervals of 24 hr, 7 day and
28 day after mixing. Human monocytes were isolated from peripheral blood
mononuclear cells and cocultered with 24 hr, 7 day and 28 day samples of
different materials for 24 and 48 hr. Cell viability was evaluated using an MTT
assay. RESULTS: In all groups, the viability of monocytes significantly improved
with increasing storage time regardless of the incubation time (p < 0.001). After
24 hr of incubation, there was no significant difference between the materials
regarding monocyte viability. However, at 48 hr of incubation, ProRoot MTA and
Biodentine were less cytotoxic than CEM cement and Biosealer (p < 0.01).
CONCLUSIONS: Biodentine and ProRoot MTA had similar biocompatibility. Mixing
ProRoot MTA with PBS in place of distilled water had no effect on its
biocompatibility. Biosealer and CEM cement after 48 hr of incubation were
significantly more cytotoxic to on monocyte cells compared to ProRoot MTA and
Biodentine.
PMID- 25110638
TI - Temperature changes under demineralized dentin during polymerization of three
resin-based restorative materials using QTH and LED units.
AB - OBJECTIVES: Light-curing of resin-based materials (RBMs) increases the pulp
chamber temperature, with detrimental effects on the vital pulp. This in vitro
study compared the temperature rise under demineralized human tooth dentin during
light-curing and the degrees of conversion (DCs) of three different RBMs using
quartz tungsten halogen (QTH) and light-emitting diode (LED) units (LCUs).
MATERIALS AND METHODS: Demineralized and non-demineralized dentin disks were
prepared from 120 extracted human mandibular molars. The temperature rise under
the dentin disks (n = 12) during the light-curing of three RBMs, i.e. an Ormocer
based composite resin (Ceram. X, Dentsply DeTrey), a low-shrinkage silorane-based
composite (Filtek P90, 3M ESPE), and a giomer (Beautifil II, Shofu GmbH), was
measured with a K-type thermocouple wire. The DCs of the materials were
investigated using Fourier transform infrared spectroscopy. RESULTS: The
temperature rise under the demineralized dentin disks was higher than that under
the non-demineralized dentin disks during the polymerization of all restorative
materials (p < 0.05). Filtek P90 induced higher temperature rise during
polymerization than Ceram.X and Beautifil II under demineralized dentin (p <
0.05). The temperature rise under demineralized dentin during Filtek P90
polymerization exceeded the threshold value (5.5C), with no significant
differences between the DCs of the test materials (p > 0.05). CONCLUSIONS:
Although there were no significant differences in the DCs, the temperature rise
under demineralized dentin disks for the silorane-based composite was higher than
that for dimethacrylate-based restorative materials, particularly with QTH LCU.
PMID- 25110639
TI - How to design in situ studies: an evaluation of experimental protocols.
AB - OBJECTIVES: Designing in situ models for caries research is a demanding
procedure, as both clinical and laboratory parameters need to be incorporated in
a single study. This study aimed to construct an informative guideline for
planning in situ models relevant to preexisting caries studies. MATERIALS AND
METHODS: An electronic literature search of the PubMed database was performed. A
total 191 of full articles written in English were included and data were
extracted from materials and methods. Multiple variables were analyzed in
relation to the publication types, participant characteristics, specimen and
appliance factors, and other conditions. Frequencies and percentages were
displayed to summarize the data and the Pearson's chi-square test was used to
assess a statistical significance (p < 0.05). RESULTS: There were many parameters
commonly included in the majority of in situ models such as inclusion criteria,
sample sizes, sample allocation methods, tooth types, intraoral appliance types,
sterilization methods, study periods, outcome measures, experimental
interventions, etc. Interrelationships existed between the main research topics
and some parameters (outcome measures and sample allocation methods) among the
evaluated articles. CONCLUSIONS: It will be possible to establish standardized in
situ protocols according to the research topics. Furthermore, data collaboration
from comparable studies would be enhanced by homogeneous study designs.
PMID- 25110640
TI - Effect of 38% carbamide peroxide on the microleakage of silorane-based versus
methacrylate-based composite restorations.
AB - OBJECTIVES: This study aimed to assess the effect of 38% carbamide peroxide on
the microleakage of class V cavities restored with either a silorane-based
composite or two methacrylate-based composites. MATERIALS AND METHODS: A total of
96 class V cavities were prepared on the buccal surface of extracted human teeth
with both enamel and dentin margins and were randomly assigned into three groups
of Filtek P90 (3M-ESPE) + P90 system adhesive (3M-ESPE)(group A), Filtek Z250 (3M
ESPE) + Adper Prompt L-Pop (3M-ESPE)(group B) and Filtek Z350XT (3M-ESPE) + Adper
Prompt L-Pop (group C). Half of the teeth were randomly underwent bleaching (38%
carbamide peroxide, Day White, Discus Dental, applying for 15 min, twice a day
for 14 day) while the remaining half (control) were not bleached. Dye penetration
was measured following immersion in basic fuchsine. Data were statistically
analyzed using Kruskal-Wallis and Mann-Whitney U tests at a level of 0.05.
RESULTS: No significant differences were found between composites in the control
groups in enamel (p = 0.171) or dentin (p = 0.094) margins. After bleaching,
microleakage of Z250 (in enamel [p = 0.867] or dentin [p = 0.590] margins) and
Z350 (in enamel [p = 0.445] or dentin [p = 0.591] margins) did not change
significantly, but the microleakage of P90 significantly increased in both enamel
(p = 0.042) and dentin (p = 0.002) margins. CONCLUSIONS: No significant
differences were noted between the bleached and control subgroups of two
methacrylate-based composites in enamel or dentin margins. Microleakage of
silorane-based composite significantly increased after bleaching.
PMID- 25110641
TI - Enamel pretreatment with Er:YAG laser: effects on the microleakage of fissure
sealant in fluorosed teeth.
AB - OBJECTIVES: The purpose of this in vitro study was to evaluate the microleakage
and penetration of fissure sealant in permanent molar teeth with fluorosis after
pretreatment of the occlusal surface. MATERIALS AND METHODS: A total of 120 third
molars with mild dental fluorosis were randomly divided into 6 groups (n = 20).
The tooth surfaces were sealed with an unfilled resin fissure sealant (FS)
material. The experimental groups included: 1) phosphoric acid etching (AE) + FS
(control); 2) AE + One-Step Plus (OS, Bisco) + FS; 3) bur + AE + FS; 4) bur + AE
+ OS + FS; 5) Er:YAG laser + AE + FS; and 6) Er:YAG laser + AE + OS + FS. After
thermocycling, the teeth were immersed in 0.5% fuchsin and sectioned. Proportions
of mircoleakage (PM) and unfilled area (PUA) were measured by digital microscope.
RESULTS: Overall, there were significant differences among all groups in the PM
(p = 0.00). Group 3 showed the greatest PM, and was significantly different from
groups 2 to 6 (p < 0.05). Group 6 showed the lowest PM. Pretreatment with Er:YAG
with or without adhesive led to less PM than bur pretreatment. There were no
significant differences among groups in PUA. CONCLUSIONS: Conventional acid
etching provided a similar degree of occlusal seal in teeth with fluorosis
compared to those pretreated with a bur or Er:YAG laser. Pretreatment of pits and
fissures with Er:YAG in teeth with fluorosis may be an alternative method before
fissure sealant application.
PMID- 25110642
TI - The effects of bone morphogenetic protein-2 and enamel matrix derivative on the
bioactivity of mineral trioxide aggregate in MC3T3-E1cells.
AB - OBJECTIVES: The effects of bone morphogenetic protein-2 (BMP-2) and enamel matrix
derivative (EMD) respectively with mineral trioxide aggregate (MTA) on hard
tissue regeneration have been investigated in previous studies. This study aimed
to compare the osteogenic effects of MTA/BMP-2 and MTA/EMD treatment in MC3T3-E1
cells. MATERIALS AND METHODS: MC3T3-E1 cells were treated with MTA (ProRoot,
Dentsply), BMP-2 (R&D Systems), EMD (Emdogain, Straumann) separately and MTA/BMP
2 or MTA/EMD combination. Mineralization was evaluated by staining the calcium
deposits with alkaline phosphatase (ALP, Sigma-Aldrich) and Alizarin red (Sigma
Aldrich). The effects on the osteoblast differentiation were evaluated by the
expressions of osteogenic markers, including ALP, bone sialoprotein (BSP),
osteocalcin (OCN), osteopontin (OPN) and osteonectin (OSN), as determined by
reverse-transcription polymerase chain reaction analysis (RT-PCR, AccuPower PCR,
Bioneer). RESULTS: Mineralization increased in the BMP-2 and MTA/BMP-2 groups and
increased to a lesser extent in the MTA/EMD group but appeared to decrease in the
MTA-only group based on Alizarin red staining. ALP expression largely decreased
in the EMD and MTA/EMD groups based on ALP staining. In the MTA/BMP-2 group, mRNA
expression of OPN on day 3 and BSP and OCN on day 7 significantly increased. In
the MTA/EMD group, OSN and OCN gene expression significantly increased on day 7,
whereas ALP expression decreased on days 3 and 7 (p < 0.05). CONCLUSIONS: These
results suggest the MTA/BMP-2 combination promoted more rapid differentiation in
MC3T3-E1 cells than did MTA/EMD during the early mineralization period.
PMID- 25110643
TI - Comparative efficacy of photo-activated disinfection and calcium hydroxide for
disinfection of remaining carious dentin in deep cavities: a clinical study.
AB - OBJECTIVES: To comparatively evaluate the efficacy of photo-activated
disinfection (PAD), calcium hydroxide (CH) and their combination on the treatment
outcome of indirect pulp treatment (IPT). MATERIALS AND METHODS: Institutional
ethical clearance and informed consent of the patients were taken. The study was
also registered with clinical registry of India. Sixty permanent molars
exhibiting deep occlusal carious lesion in patients with the age range of 18 - 22
yr were included. Clinical and radiographic evaluation and set inclusion and
exclusion criteria's were followed. Gross caries excavation was accomplished. In
group I (n = 20) PAD was applied for sixty seconds. In group II (n = 20), CH was
applied to the remaining carious dentin, while in group III (n = 20), PAD
application was followed by CH placement. The teeth were permanently restored.
They were clinically and radiographically followed-up at 45 day, 6 mon and 12
mon. Relative density of the remaining affected dentin was measured by
'Radiovisiography (RVG) densitometric' analysis. RESULTS: Successful outcome with
an increase in radiographic grey values were observed in all three groups.
However, on inter-group comparison, this change was not significant (p > 0.05).
CONCLUSIONS: PAD and CH both have equal disinfection efficacy in the treatment of
deep carious dentin. PAD alone is as effective for treatment of deep carious
lesion as calcium hydroxide and hence can be used as an alternative to CH. They
can be used independently in IPT, since combining both does not offer any
additional therapeutic benefits.
PMID- 25110644
TI - Comparative analysis of physicochemical properties of root perforation sealer
materials.
AB - OBJECTIVES: This study evaluated the solubility, dimensional alteration, pH,
electrical conductivity, and radiopacity of root perforation sealer materials.
MATERIALS AND METHODS: For the pH test, the samples were immersed in distilled
water for different periods of time. Then, the samples were retained in plastic
recipients, and the electrical conductivity of the solution was measured. The
solubility, dimensional alteration, and radiopacity properties were evaluated
according to Specification No. 57 of the American National Standards
Institute/American Dental Association (ANSI/ADA). Statistical analyses were
carried out using analysis of variance (ANOVA) and Tukey's test at a significance
level of 5%. When the sample distribution was not normal, a nonparametric ANOVA
was performed with a Kruskal-Wallis test (alpha = 0.05). RESULTS: The results
showed that white structural Portland cement (PC) had the highest solubility,
while mineral trioxide aggregate (MTA)-based cements, ProRoot MTA (Dentsply-Tulsa
Dental) and MTA BIO (Angelus Ind. Prod.), had the lowest values. MTA BIO showed
the lowest dimensional alteration values and white PC presented the highest
values. No differences among the tested materials were observed in the the pH and
electrical conductivity analyses. Only the MTA-based cements met the ANSI/ADA
recommendations regarding radiopacity, overcoming the three steps of the aluminum
step wedge. CONCLUSIONS: On the basis of these results, we concluded that the
values of solubility and dimensional alteration of the materials were in
accordance with the ANSI/ADA specifications. PCs did not fulfill the ANSI/ADA
requirements regarding radiopacity. No differences were observed among the
materials with respect to the pH and electrical conductivity analyses.
PMID- 25110645
TI - Prevalence of referral reasons and clinical symptoms for endodontic referrals.
AB - OBJECTIVES: To investigate the prevalence of different primary reasons for
endodontic referrals and the clinical symptoms of the referred cases. MATERIALS
AND METHODS: Clinical data of total endodontic treatment cases (1,014 teeth)
including endodontic referral cases (224 teeth) between January 1, 2010 and
December 31, 2012, at Kangdong Sacred Heart Hospital, were investigated
retrospectively. The one major reason for referral, the clinical symptoms, and
the resulting treatment procedures of referral cases were recorded. The
percentages of clinical symptoms of the endodontic referral cases and the total
endodontic treatment cases were compared by chi(2) test for each symptom.
RESULTS: Persistent pain was the most frequent reason for endodontic referral
(29.5%), followed by presence of gingival swelling and sinus tract (24.1%), and
apical radiolucency (12.9%). Referrals in cases involving endodontic difficulties
such as canal calcification, broken instruments, post, perforation, and
resorption were less than 5.0%, respectively. The percentages of four major
clinical symptoms of pain, apical radiolucency, previous endodontic treatment,
and gingival swelling and sinus tract were significantly higher in the endodontic
referral cases than those in the total endodontic cases (p = 0.001). Among the
included referral cases, 72.8% were treated with nonsurgical endodontic treatment
only. Teeth other than the referred teeth were diagnosed as the origin of the
problem in 5.8% of the referrals. CONCLUSIONS: The high prevalence of pain,
apical radiolucency, previous treatment, and gingival swelling and sinus tract in
endodontic referral cases suggest that these symptoms may be what general
practitioners consider to be difficult and refer to endodontists.
PMID- 25110646
TI - Mental nerve paresthesia secondary to initiation of endodontic therapy: a case
report.
AB - Whenever endodontic therapy is performed on mandibular posterior teeth, damage to
the inferior alveolar nerve or any of its branches is possible. Acute periapical
infection in mandibular posterior teeth may also sometimes disturb the normal
functioning of the inferior alveolar nerve. The most common clinical
manifestation of these insults is the paresthesia of the inferior alveolar nerve
or mental nerve paresthesia. Paresthesia usually manifests as burning, prickling,
tingling, numbness, itching or any deviation from normal sensation. Altered
sensation and pain in the involved areas may interfere with speaking, eating,
drinking, shaving, tooth brushing and other events of social interaction which
will have a disturbing impact on the patient. Paresthesia can be short term, long
term or even permanent. The duration of the paresthesia depends upon the extent
of the nerve damage or persistence of the etiology. Permanent paresthesia is the
result of nerve trunk laceration or actual total nerve damage. Paresthesia must
be treated as soon as diagnosed to have better treatment outcomes. The present
paper describes a case of mental nerve paresthesia arising after the start of the
endodontic therapy in left mandibular first molar which was managed successfully
by conservative treatment.
PMID- 25110647
TI - Esthetic rehabilitation of single anterior edentulous space using fiber
reinforced composite.
AB - A fiber-reinforced composite (FRC) fixed prosthesis is an innovative alternative
to a traditional metal restoration, as it is a conservative treatment method.
This case report demonstrates a detailed procedure for restoring a missing
anterior tooth with an FRC. A 44-year-old woman visited our department with an
avulsed tooth that had fallen out on the previous day and was completely dry.
This tooth was replanted, but it failed after one year. A semi-direct technique
was used to fabricate a FRC fixed partial prosthesis for its replacement. The FRC
framework and the pontic were fabricated using a duplicated cast model and
nanofilled composite resin. Later on, interproximal contact, tooth shape, and
shade were adjusted at chairside. This technique not only enables the clinician
to replace a missing tooth immediately after extraction for minimizing esthetic
problems, but it also decreases both tooth reduction and cost.
PMID- 25110648
TI - An esthetic appliance for the management of crown-root fracture: a case report.
AB - Orthodontic extrusion is usually performed by means of a fixed orthodontic
appliance that utilizes arch wire attached to adjacent teeth and transfers the
desired force by elastic from the wire to the root. However, clinicians often
encounter cases where the bonding required for tooth traction is not possible
because the adjacent teeth have been restored with ceramic or veneer. The purpose
of this case report is to describe a modified orthodontic extrusion appliance
that is useful when conventional orthodontic treatment is not possible. The
modified appliance was fabricated using an artificial tooth, clear plastic
sheeting, and a braided fiber-reinforced composite strip that covered adjacent
teeth without bonding. It satisfied the esthetic and functional needs of the
patient and established the optimal biologic width.
PMID- 25110650
TI - Statistical notes for clinical researchers: Nonparametric statistical methods: 1.
Nonparametric methods for comparing two groups.
PMID- 25110649
TI - The use of platelet rich plasma in the treatment of immature tooth with
periapical lesion: a case report.
AB - This study describes the treatment of an immature permanent tooth with periapical
lesion which was treated with regenerative approach using platelet rich plasma
(PRP). The root canal of immature human permanent tooth with periapical lesion
was gently debrided of necrotic tissue and disinfected with 2.5% NaOCl, and then
medicated with triple antibiotic paste comprised of ciprofloxacin, metronidazole,
and tetracycline. When the tooth was asymptomatic, PRP and mineral trioxide
aggregate (MTA) were placed into the root canal. Six months after PRP treatment,
radiographical examination revealed resolution of the radiolucency and
progressive thickening of the root wall and apical closure. Our findings suggest
that PRP can be used for the treatment of immature permanent teeth with
periapical lesion, as part of a regenerative endodontic treatment procedure.
PMID- 25110651
TI - Rotational stability of endodontic motors.
PMID- 25110652
TI - Identification of Differentially Expressed Gene after Femoral Fracture via
Microarray Profiling.
AB - We aimed to investigate differentially expressed genes (DEGs) in different stages
after femoral fracture based on rat models, providing the basis for the treatment
of sport-related fractures. Gene expression data GSE3298 was downloaded from Gene
Expression Omnibus (GEO), including 16 chips. All femoral fracture samples were
classified into earlier fracture stage and later fracture stage. Total 87 DEGs
simultaneously occurred in two stages, of which 4 genes showed opposite
expression tendency. Out of the 4 genes, Rest and Cst8 were hub nodes in protein
protein interaction (PPI) network. The GO (Gene Ontology) function enrichment
analysis verified that nutrition supply related genes were enriched in the
earlier stage and neuron growth related genes were enriched in the later stage.
Calcium signaling pathway was the most significant pathway in earlier stage; in
later stage, DEGs were enriched into 2 neurodevelopment-related pathways.
Analysis of Pearson's correlation coefficient showed that a total of 3,300 genes
were significantly associated with fracture time, none of which was overlapped
with identified DEGs. This study suggested that Rest and Cst8 might act as
potential indicators for fracture healing. Calcium signaling pathway and
neurodevelopment-related pathways might be deeply involved in bone healing after
femoral fracture.
PMID- 25110653
TI - Stereotactic body radiotherapy for small lung tumors in the University of Tokyo
Hospital.
AB - Our work on stereotactic body radiation therapy (SBRT) for primary and metastatic
lung tumors will be described. The eligibility criteria for SBRT, our previous
SBRT method, the definition of target volume, heterogeneity correction, the
position adjustment using four-dimensional cone-beam computed tomography (4D
CBCT) immediately before SBRT, volumetric modulated arc therapy (VMAT) method for
SBRT, verifying of tumor position within internal target volume (ITV) using in
treatment 4D-CBCT during VMAT-SBRT, shortening of treatment time using flattening
filter-free (FFF) techniques, delivery of 4D dose calculation for lung-VMAT
patients using in-treatment CBCT and LINAC log data with agility multileaf
collimator, and SBRT method for centrally located lung tumors in our institution
will be shown. In our institution, these efforts have been made with the goal of
raising the local control rate and decreasing adverse effects after SBRT.
PMID- 25110654
TI - Evaluation of cocktails with recombinant proteins of Mycobacterium bovis for a
specific diagnosis of bovine tuberculosis.
AB - The Delayed type hypersensitivity skin test (DTH) and interferon-gamma assay are
used for the diagnosis of bovine tuberculosis (TBB). The specificity of these
diagnoses, however, is compromised because both are based on the response against
purified protein derivative of Mycobacterium bovis (PPD-B). In this study, we
assessed the potential of two cocktails containing M. bovis recombinant proteins:
cocktail 1 (C1): ESAT-6, CFP-10 and MPB83 and cocktail 2 (C2): ESAT-6, CFP-10,
MPB83, HspX, TB10.3, and MPB70. C1, C2, and PPD-B showed similar response by DTH
in M. bovis-sensitized guinea pigs. Importantly, C1 induced a lower response than
PPD-B in M. avium-sensitized guinea pigs. In cattle, C1 displayed better
performance than PPD-B and C2; indeed, C1 showed the least detection of animals
either vaccinated or Map-infected. To optimize the composition of the cocktails,
we obtained protein fractions from PPD-B and tested their immunogenicity in
experimentally M. bovis-infected cattle. In one highly reactive fraction, seven
proteins were identified. The inclusion of FixB in C1 enhanced the recognition of
M. bovis-infected cattle without compromising specificity. Our data provide a
promising basis for the future development of a cocktail for TBB detection
without interference by the presence of sensitized or infected animals with other
mycobacteria.
PMID- 25110655
TI - Development and characterization of novel porous 3D alginate-cockle shell powder
nanobiocomposite bone scaffold.
AB - A novel porous three-dimensional bone scaffold was developed using a natural
polymer (alginate/Alg) in combination with a naturally obtained biomineral (nano
cockle shell powder/nCP) through lyophilization techniques. The scaffold was
developed in varying composition mixture of Alg-nCP and characterized using
various evaluation techniques as well as preliminary in vitro studies on MG63
human osteoblast cells. Morphological observations using SEM revealed variations
in structures with the use of different Alg-nCP composition ratios. All the
developed scaffolds showed a porous structure with pore sizes ideal for
facilitating new bone growth; however, not all combination mixtures showed
subsequent favorable characteristics to be used for biological applications.
Scaffolds produced using the combination mixture of 40% Alg and 60% nCP produced
significantly promising results in terms of mechanical strength, degradation
rate, and increased cell proliferation rates making it potentially the optimum
composition mixture of Alg-nCP with future application prospects.
PMID- 25110656
TI - Assessment of food processing and pharmaceutical industrial wastes as potential
biosorbents: a review.
AB - There is a growing need for the use of low-cost and ecofriendly adsorbents in
water/wastewater treatment applications. Conventional adsorbents as well as
biosorbents from different natural and agricultural sources have been extensively
studied and reviewed. However, there is a lack of reviews on biosorption
utilizing industrial wastes, particularly those of food processing and
pharmaceuticals. The current review evaluates the potential of these wastes as
biosorbents for the removal of some hazardous contaminants. Sources and
applications of these biosorbents are presented, while factors affecting
biosorption are discussed. Equilibrium, kinetics, and mechanisms of biosorption
are also reviewed. In spite of the wide spread application of these biosorbents
in the treatment of heavy metals and dyes, more research is required on other
classes of pollutants. In addition, further work should be dedicated to studying
scaling up of the process and its economic feasibility. More attention should
also be given to enhancing mechanical strength, stability, life time, and
reproducibility of the biosorbent. Environmental concerns regarding disposal of
consumed biosorbents should be addressed by offering feasible biosorbent
regeneration or pollutant immobilization options.
PMID- 25110657
TI - The effects of apigenin on the expression of Fas/FasL apoptotic pathway in warm
liver ischemia-reperfusion injury in rats.
AB - BACKGROUND: The aim of this experimental study was to investigate the role of
apigenin in liver apoptosis, in an experimental model of hepatic ischemia
reperfusion in rats. MATERIALS AND METHODS: Forty-eight Wistar rats (apigenin and
control groups), 14 to 16 weeks old and weighing 220 to 350 g, were used. They
were all subjected to hepatic ischemia by occlusion of the hepatic artery and
portal vein for 45 minutes and reperfusion was followed for 60, 120, and 240
minutes. Apigenin was administrated intraperitoneally. Liver tissues were used
for the detection of apoptosis by TUNEL assay and caspase 3 antibodies.
Expression analysis of Fas/FasL genes was evaluated by real time PCR. RESULTS:
The expression analysis of Fas and FasL genes was increasing during reperfusion
(significantly in the group of 240 minutes of reperfusion). It was in the same
group that apigenin decreased Fas receptor levels and inhibited apoptosis as
confirmed by TUNEL assay and caspase 3 antibodies. CONCLUSIONS: The effects of
apigenin in the Fas/FasL mediated pathway of apoptosis, in the hepatic ischemia
reperfusion, seem to have a protective result on the hepatic cell.
PMID- 25110658
TI - The role of microclot formation in an acute subarachnoid hemorrhage model in the
rabbit.
AB - BACKGROUND: Microvascular dysfunction and microthrombi formation are believed to
contribute to development of early brain injury (EBI) after aneurysmal
subarachnoid hemorrhage (SAH). OBJECTIVE: This study aimed to determine (i)
extent of microthrombus formation and neuronal apoptosis in the brain parenchyma
using a blood shunt SAH model in rabbits; (ii) correlation of structural changes
in microvessels with EBI characteristics. METHODS: Acute SAH was induced using a
rabbit shunt cisterna magna model. Extent of microthrombosis was detected 24 h
post-SAH (n = 8) by fibrinogen immunostaining, compared to controls (n = 4). We
assessed apoptosis by terminal deoxynucleotidyl transferase nick end labeling
(TUNEL) in cortex and hippocampus. RESULTS: Our results showed significantly more
TUNEL-positive cells (SAH: 115 +/- 13; controls: 58 +/- 10; P = 0.016) and
fibrinogen-positive microthromboemboli (SAH: 9 +/- 2; controls: 2 +/- 1; P =
0.03) in the hippocampus after aneurysmal SAH. CONCLUSIONS: We found clear
evidence of early microclot formation in a rabbit model of acute SAH. The extent
of microthrombosis did not correlate with early apoptosis or CPP depletion after
SAH; however, the total number of TUNEL positive cells in the cortex and the
hippocampus significantly correlated with mean CPP reduction during the phase of
maximum depletion after SAH induction. Both microthrombosis and neuronal
apoptosis may contribute to EBI and subsequent DCI.
PMID- 25110659
TI - Risk factors for mortality in patients with septic acute kidney injury in
intensive care units in Beijing, China: a multicenter prospective observational
study.
AB - OBJECTIVE: To discover risk factors for mortality of patients with septic AKI in
ICU via a multicenter study. BACKGROUND: Septic AKI is a serious threat to
patients in ICU, but there are a few clinical studies focusing on this. METHODS:
This was a prospective, observational, and multicenter study conducted in 30 ICUs
of 28 major hospitals in Beijing. 3,107 patients were admitted consecutively,
among which 361 patients were with septic AKI. Patient clinical data were
recorded daily for 10 days after admission. Kidney Disease: Improving Global
Outcomes (KDIGO) criteria were used to define and stage AKI. Of the involved
patients, 201 survived and 160 died. RESULTS: The rate of septic AKI was 11.6%.
Twenty-one risk factors were found, and six independent risk factors were
identified: age, APACHE II score, duration of mechanical ventilation, duration of
MAP <65 mmHg, time until RRT started, and progressive KIDGO stage. Admission
KDIGO stages were not associated with mortality, while worst KDIGO stages were.
Only progressive KIDGO stage was an independent risk factor. CONCLUSIONS: Six
independent risk factors for mortality for septic AKI were identified.
Progressive KIDGO stage is better than admission or the worst KIDGO for
prediction of mortality. This trial is registered with ChiCTR-ONC-11001875.
PMID- 25110660
TI - Beta-thalassaemia intermedia: evaluation of endocrine and bone complications.
AB - OBJECTIVE: Data about endocrine and bone disease in nontransfusion-dependent
thalassaemia (NTDT) is scanty. The aim of our study was to evaluate these
complications in beta-TI adult patients. METHODS: We studied retrospectively 70
beta-TI patients with mean followup of 20 years. Data recorded included age,
gender, haemoglobin and ferritin levels, biochemical and endocrine tests, liver
iron concentration (LIC) from T2*, transfusion regimen, iron chelation,
hydroxyurea, splenectomy, and bone mineralization by dual X-ray absorptiometry.
RESULTS: Thirty-seven (53%) males and 33 (47%) females were studied, with mean
age 41 +/- 12 years, mean haemoglobin 9.2 +/- 1.5 g/dL, median ferritin 537
(range 14-4893), and mean LIC 7.6 +/- 6.4 mg Fe/g dw. Thirty-three patients (47%)
had been transfused, occasionally (24/33; 73%) or regularly (9/33; 27%); 37/70
(53%) had never been transfused; 34/70 patients had been splenectomized (49%); 39
(56%) were on chelation therapy; and 11 (16%) were on hydroxyurea.
Endocrinopathies were found in 15 patients (21%): 10 hypothyroidism, 3
hypogonadism, 2 impaired glucose tolerance (IGT), and one diabetes. Bone disease
was observed in 53/70 (76%) patients, osteoporosis in 26/53 (49%), and osteopenia
in 27/53 (51%). DISCUSSION AND CONCLUSIONS: Bone disease was found in most
patients in our study, while endocrinopathies were highly uncommon, especially
hypogonadism. We speculate that low iron burden may protect against
endocrinopathy development.
PMID- 25110661
TI - Mechatronic feasibility of minimally invasive, atraumatic cochleostomy.
AB - Robotic assistance in the context of lateral skull base surgery, particularly
during cochlear implantation procedures, has been the subject of considerable
research over the last decade. The use of robotics during these procedures has
the potential to provide significant benefits to the patient by reducing
invasiveness when gaining access to the cochlea, as well as reducing
intracochlear trauma when performing a cochleostomy. Presented herein is
preliminary work on the combination of two robotic systems for reducing
invasiveness and trauma in cochlear implantation procedures. A robotic system for
minimally invasive inner ear access was combined with a smart drilling tool for
robust and safe cochleostomy; evaluation was completed on a single human cadaver
specimen. Access to the middle ear was successfully achieved through the facial
recess without damage to surrounding anatomical structures; cochleostomy was
completed at the planned position with the endosteum remaining intact after
drilling as confirmed by microscope evaluation.
PMID- 25110662
TI - A novel COL4A5 mutation identified in a Chinese Han family using exome
sequencing.
AB - Alport syndrome (AS) is a monogenic disease of the basement membrane (BM),
resulting in progressive renal failure due to glomerulonephropathy, variable
sensorineural hearing loss, and ocular anomalies. It is caused by mutations in
the collagen type IV alpha-3 gene (COL4A3), the collagen type IV alpha-4 gene
(COL4A4), and the collagen type IV alpha-5 gene (COL4A5), which encodes type IV
collagen alpha3, alpha4, and alpha5 chains, respectively. To explore the disease
related gene in a four-generation Chinese Han pedigree of AS, exome sequencing
was conducted on the proband, and a novel deletion mutation c.499delC
(p.Pro167Glnfs*36) in the COL4A5 gene was identified. This mutation, absent in
1,000 genomes project, HapMap, dbSNP132, YH1 databases, and 100 normal controls,
cosegregated with patients in the family. Neither sensorineural hearing loss nor
typical COL4A5-related ocular abnormalities (dot-and-fleck retinopathy, anterior
lenticonus, and the rare posterior polymorphous corneal dystrophy) were present
in patients of this family. The phenotypes of patients in this AS family were
characterized by early onset-age and rapidly developing into end-stage renal
disease (ESRD). Our discovery broadens the mutation spectrum in the COL4A5 gene
associated with AS, which may also shed new light on genetic counseling for AS.
PMID- 25110663
TI - The impact of tobacco smoke exposure on wheezing and overweight in 4-6-year-old
children.
AB - AIM: To investigate the association between maternal smoking during pregnancy,
second-hand tobacco smoke (STS) exposure, education level, and preschool
children's wheezing and overweight. METHODS: This cohort study used data of the
KANC cohort--1,489 4-6-year-old children from Kaunas city, Lithuania.
Multivariate logistic regression was employed to study the influence of prenatal
and postnatal STS exposure on the prevalence of wheezing and overweight,
controlling for potential confounders. RESULTS: Children exposed to maternal
smoking during pregnancy had a slightly increased prevalence of wheezing and
overweight. Postnatal exposure to STS was associated with a statistically
significantly increased risk of wheezing and overweight in children born to
mothers with lower education levels (OR 2.12; 95% CI 1.04-4.35 and 3.57; 95% CI
1.76-7.21, accordingly). CONCLUSIONS: The present study findings suggest that
both maternal smoking during pregnancy and STS increase the risk of childhood
wheezing and overweight, whereas lower maternal education might have a synergetic
effect. Targeted interventions must to take this into account and address
household smoking.
PMID- 25110664
TI - Cloning, expression, purification, and characterization of glutaredoxin from
Antarctic sea-ice bacterium Pseudoalteromonas sp. AN178.
AB - Glutaredoxins (Grxs) are small ubiquitous redox enzymes that catalyze glutathione
dependent reactions to reduce protein disulfide. In this study, a full-length Grx
gene (PsGrx) with 270 nucleotides was isolated from Antarctic sea-ice bacterium
Pseudoalteromonas sp. AN178. It encoded deduced 89 amino acid residues with the
molecular weight 9.8 kDa. Sequence analysis of the amino acid sequence revealed
the catalytic motif CPYC. Recombinant PsGrx (rPsGrx) stably expressed in E. coli
BL21 was purified to apparent homogeneity by Ni-affinity chromatography. rPsGrx
exhibited optimal activity at 30 degrees C and pH 8.0 and showed 25.5% of the
activity at 0 degrees C. It retained 65.0% of activity after incubation at 40
degrees C for 20 min and still exhibited 37.0% activity in 1.0 M NaCl. These
results indicated that rPsGrx was a typical cold active protein with low
thermostability.
PMID- 25110665
TI - Emerging microbial concerns in food safety and new control measures.
PMID- 25110666
TI - Evaluation of growth patterns and body composition in C57Bl/6J mice using dual
energy X-ray absorptiometry.
AB - The normal growth pattern of female C57BL/6J mice, from 5 to 30 weeks of age, has
been investigated in a longitudinal study. Weight, body surface area (BS), and
body mass index (BMI) were evaluated in forty mice. Lean mass and fat mass, bone
mineral content (BMC), and bone mineral density (BMD) were monitored by dual
energy X-ray absorptiometry (DEXA). Weight and BS increased linearly (16.15 +/-
0.64-27.64 +/- 1.42 g; 51.13 +/- 0.74-79.57 +/- 2.15 cm(2), P < 0.01), more
markedly from 5 to 9 weeks of age (P < 0.001). BMD showed a peak at 17 weeks
(0.0548 +/- 0.0011 g/cm(2) * m, P < 0.01). Lean mass showed an evident gain at 9
(15.8 +/- 0.8 g, P < 0.001) and 25 weeks (20.5 +/- 0.3 g, P < 0.01), like fat
mass from 13 to 17 weeks (2.0 +/- 0.4-3.6 +/- 0.7 g, P < 0.01). BMI and lean mass
index (LMI) reached the highest value at 21 weeks (3.57 +/- 0.02-0.284 +/- 0.010
g/cm(2), resp.), like fat mass index (FMI) at 17 weeks (0.057 +/- 0.009 g/cm(2))
(P < 0.01). BMI, weight, and BS showed a moderate positive correlation (0.45
0.85) with lean mass from 5 to 21 weeks. Mixed linear models provided a good
prediction for lean mass, fat mass, and BMD. This study may represent a baseline
reference for a future comparison of wild-type C57BL/6J mice with models of
altered growth.
PMID- 25110667
TI - Usefulness of anticoagulant therapy in the prevention of embolic complications in
patients with acute infective endocarditis.
AB - BACKGROUND: The use of anticoagulant therapy (ACT) in patients with acute
infective endocarditis (IE) remains a controversial issue. Our study attempts to
estimate the impact of ACT on the occurrence of embolic complications and the
usefulness of ACT in the prevention of embolism in IE patients. METHODS: The
present authors analyzed 150 patients with left-sided IE. Embolisms including
cerebrovascular events (CVE) and the use of ACT were checked at the time of
admission and during hospitalization. RESULTS: 57 patients (38.0%) experienced an
embolic event. There was no significant difference in the incidence of CVE and in
hospital mortality between patients with and without warfarin use at admission,
although warfarin-naive patients were significantly more likely to have large (>1
cm) and mobile vegetation. In addition, there was no significant difference in
the incidence of postadmission embolism and in-hospital death between patients
with and without in-hospital ACT. On multivariate logistic regression analysis,
ACT at admission was not significantly associated with a lower risk of embolism
in patients with IE. CONCLUSIONS: The role of ACT in the prevention of embolism
was limited in IE patients undergoing antibiotic therapy, although it seems to
reduce the embolic potential of septic vegetation before treatment.
PMID- 25110668
TI - Assessment of the optic disc morphology using spectral-domain optical coherence
tomography and scanning laser ophthalmoscopy.
AB - OBJECTIVE: To compare the equivalent optic nerve head (OHN) parameters obtained
with confocal scanning laser ophthalmoscopy (HRT3) and spectral-domain optical
coherence tomography (OCT) in healthy and glaucoma patients. METHODS: One hundred
and eighty-two consecutive healthy subjects and 156 patients with open-angle
glaucoma were divided into 2 groups according to intraocular pressure and visual
field outcomes. All participants underwent imaging of the ONH with the HRT3 and
the Cirrus OCT. The ONH parameters and the receiver operating characteristic
(ROC) curves were compared between both groups. RESULTS: Mean age did not differ
between the normal and glaucoma groups (59.55 +/- 9.7 years and 61.05 +/- 9.4
years, resp.; P = 0.15). Rim area, average cup-to-disc (C/D) ratio, vertical C/D
ratio, and cup volume were different between both instruments (P < 0.001). All
equivalent ONH parameters, except disc area, were different between both groups
(P < 0.001). The best areas under the ROC curve were observed for vertical C/D
ratio (0.980 for OCT and 0.942 for HRT3; P = 0.11). Sensitivities at 95% fixed
specificities of OCT parameters were higher than those of HRT3. CONCLUSIONS:
Equivalent ONH parameters of Cirrus OCT and HRT3 are different and cannot be used
interchangeably. ONH parameters measured with OCT yielded a slightly better
diagnostic performance.
PMID- 25110669
TI - Mycobacterium tuberculosis P-type ATPases: possible targets for drug or vaccine
development.
AB - Tuberculosis (TB) has been the biggest killer in the human history; currently,
Mycobacterium tuberculosis (Mtb) kills nearly 2 million people each year
worldwide. The high prevalence of TB obligates the identification of new
therapeutic targets and the development of anti-TB vaccines that can control
multidrug resistance and latent TB infections. Membrane proteins have recently
been suggested as key targets for bacterial viability. Current studies have shown
that mycobacteria P-type ATPases may play critical roles in ion homeostasis and
in the response of mycobacteria to toxic substances in the intraphagosomal
environment. In this review, we bring together the genomic, transcriptomic, and
structural aspects of the P-type ATPases that are relevant during active and
latent Mtb infections, which can be useful in determining the potential of these
ATPases as drug targets and in uncovering their possible roles in the development
of new anti-TB attenuated vaccines.
PMID- 25110670
TI - Preparation of three-dimensional vascularized MSC cell sheet constructs for
tissue regeneration.
AB - Engineering three-dimensional (3D) vascularized constructs remains a challenge
due to the inability to form rich microvessel networks. In this study we
engineered a prevascularized 3D cell sheet construct for tissue regeneration
using human bone marrow-derived mesenchymal stem cells (hMSCs) and human
umbilical vein endothelial cells as cell sources. hMSCs were cultured to form a
thick cell sheet, and human umbilical vein endothelial cells (HUVECs) were then
seeded on the hMSCs sheet to form networks. The single prevascularized HUVEC/hMSC
cell sheet was folded to form a 3D construct by a modified cell sheet engineering
technique. In vitro results indicated that the hMSCs cell sheet promoted the
HUVECs cell migration to form networks in horizontal and vertical directions. In
vivo results showed that many blood vessels grew into the 3D HUVEC/hMSC cell
sheet constructs after implanted in the subcutaneous pocket of immunodeficient
mice. The density of blood vessels in the prevascularized constructs was higher
than that in the nonprevascularized constructs. Immunohistochemistry staining
further showed that in vitro preformed human capillaries in the prevascularized
constructs anastomosed with the host vasculature to form functional blood
vessels. These results suggest the promising potential of this 3D prevascularized
construct using hMSCs cell sheet as a platform for wide applications in
engineering vascularized tissues.
PMID- 25110671
TI - Tick-borne encephalitis virus habitats in North East Germany: reemergence of TBEV
in ticks after 15 years of inactivity.
AB - The incidence of tick-borne encephalitis has risen in Europe since 1990 and the
tick-borne encephalitis virus (TBEV) has been documented to be spreading into
regions where it was not previously endemic. In Mecklenburg-West Pomerania, a
federal state in Northern Germany, TBEV was not detectable in over 16,000
collected ticks between 1992 and 2004. Until 2004, the last human case of TBE in
the region was reported in 1985. Following the occurrence of three autochthonous
human cases of TBE after 2004, however, we collected ticks from the areas in
which the infections were contracted. To increase the chance of detecting TBEV
RNA, some of the ticks were fed on mice. Using nested RT-PCR, we were able to
confirm the presence of TBEV in ticks for the first time after 15 years. A
phylogenetic analysis revealed a close relationship between the sequences we
obtained and a TBEV sequence from Mecklenburg-East Pomerania published in 1992
and pointed to the reemergence of a natural focus of TBEV after years of low
activity. Our results imply that natural foci of TBEV may either persist at low
levels of activity for years or reemerge through the agency of migrating birds.
PMID- 25110672
TI - Noninvasive and quantitative assessment of in vivo fetomaternal interface
angiogenesis using RGD-based fluorescence.
AB - Angiogenesis is a key process for proper placental development and for the
success of pregnancy. Although numerous in vitro methods have been developed for
the assessment of this process, relatively few reliable in vivo methods are
available to evaluate this activity throughout gestation. Here we report an in
vivo technique that specifically measures placental neovascularization. The
technique is based on the measurement of a fluorescent alpha v beta 3
(alphavbeta3) integrin-targeting molecule called Angiolone-Alexa-Fluor 700. The
alphavbeta3 integrin is highly expressed by endothelial cells during the
neovascularization and by trophoblast cells during their invasion of the maternal
decidua. Angiolone was injected to gravid mice at 6.5 and 11.5 days post coitus
(dpc). The fluorescence was analyzed one day later at 7.5 and 12.5 dpc,
respectively. We demonstrated that (i) Angiolone targets alphavbeta3 protein in
the placenta with a strong specificity, (ii) this technique is quantitative as
the measurement was correlated to the increase of the placental size observed
with increasing gestational age, and (iii) information on the outcome is
possible, as abnormal placentation could be detected early on during gestation.
In conclusion, we report the validation of a new noninvasive and quantitative
method to assess the placental angiogenic activity, in vivo.
PMID- 25110673
TI - The effect of maternal healthcare on the probability of child survival in
Azerbaijan.
AB - This study assesses the effects of maternal healthcare on child survival by using
nonrandomized data from a cross-sectional survey in Azerbaijan. Using 2SLS and
simultaneous equation bivariate probit models, we estimate the effects of
delivering in healthcare facility on probability of child survival taking into
account self-selection into the treatment. For women who delivered at healthcare
facilities, the probability of child survival increases by approximately 18%.
Furthermore, if every woman had the opportunity to deliver in healthcare
facility, then the probability of child survival in Azerbaijan as a whole would
have increased by approximately 16%.
PMID- 25110675
TI - Changes in cortical thickness in 6-year-old children open their mind to a global
vision of the world.
AB - Even if objectively presented with similar visual stimuli, children younger than
6 years of age exhibit a strong attraction to local visual information (e.g., the
trees), whereas children older than 6 years of age, similar to adults, exhibit a
visual bias toward global information (e.g., the forest). Here, we studied the
cortical thickness changes that underlie this bias shift from local to global
visual information. Two groups, matched for age, gender, and handedness, were
formed from a total of 30 children who were 6 years old, and both groups
performed a traditional global/local visual task. The first group presented a
local visual bias, and the other group presented a global visual bias. The
results indicated that, compared with the local visual bias group, children with
a global visual bias exhibited (1) decreased cortical thickness in the bilateral
occipital regions and (2) increased cortical thickness in the left frontoparietal
regions. These findings constitute the first structural study that supports the
view that both synaptic pruning (i.e., decreased cortical thickness) and
expansion mechanisms (i.e., increased cortical thickness) cooccur to allow
healthy children to develop a global perception of the visual world.
PMID- 25110676
TI - Radiosynthesis of [18)F]trifluoroalkyl groups: scope and limitations.
AB - The present paper is concerned with radiochemical methodology to furnish the
trifluoromethyl motif labelled with (18)F. Literature spanning the last four
decades is comprehensively reviewed and radiochemical yields and specific
activities are discussed.
PMID- 25110674
TI - Role of lectin-like oxidized low density lipoprotein-1 in fetoplacental vascular
dysfunction in preeclampsia.
AB - The bioavailability of nitric oxide (NO) represents a key marker in vascular
health. A decrease in NO induces a pathological condition denominated endothelial
dysfunction, syndrome observed in different pathologies, such as obesity,
diabetes, kidney disease, cardiovascular disease, and preeclampsia (PE). PE is
one of the major risks for maternal death and fetal loss. Recent studies suggest
that the placenta of pregnant women with PE express high levels of lectin-like
oxidized LDL receptor-1 (LOX-1), which induces endothelial dysfunction by
increasing reactive oxygen species (ROS) and decreasing intracellular NO. Besides
LOX-1 activation induces changes in migration and apoptosis of
syncytiotrophoblast cells. However, the role of this receptor in placental tissue
is still unknown. In this review we will describes the physiological roles of LOX
1 in normal placenta development and the potential involvement of this receptor
in the pathophysiology of PE.
PMID- 25110677
TI - Beneficial effects of testosterone therapy on functional capacity, cardiovascular
parameters, and quality of life in patients with congestive heart failure.
AB - BACKGROUND: According to the present evidences suggesting association between low
testosterone level and prediction of reduced exercise capacity as well as poor
clinical outcome in patients with heart failure, we sought to determine if
testosterone therapy improves clinical and cardiovascular conditions as well as
quality of life status in patients with stable chronic heart failure. METHODS: A
total of 50 male patients who suffered from congestive heart failure were
recruited in a double-blind, placebo-controlled trial and randomized to receive
an intramuscular (gluteal) long-acting androgen injection (1 mL of testosterone
enanthate 250 mg/mL) once every four weeks for 12 weeks or receive intramuscular
injections of saline (1 mL of 0.9% wt/vol NaCl) with the same protocol. RESULTS:
The changes in body weight, hemodynamic parameters, and left ventricular
dimensional echocardiographic indices were all comparable between the two groups.
Regarding changes in diastolic functional state and using Tei index, this
parameter was significantly improved. Unlike the group received placebo, those
who received testosterone had a significant increasing trend in 6-walk mean
distance (6MWD) parameter within the study period (P = 0.019). The discrepancy in
the trends of changes in 6MWD between study groups remained significant after
adjusting baseline variables (mean square = 243.262, F index = 4.402, and P =
0.045). CONCLUSION: Our study strengthens insights into the beneficial role of
testosterone in improvement of functional capacity and quality of life in heart
failure patients.
PMID- 25110678
TI - Effects of anti-TNF alpha drugs on disability in patients with rheumatoid
arthritis: long-term real-life data from the Lorhen Registry.
AB - This study involving 1033 patients with RA confirms the effectiveness of
etanercept, adalimumab, and infliximab in reducing RA-related disability even in
patients with a history of highly active and longstanding RA. Moreover, we found
that the improvement in disability was biphasic, with a marked improvement during
the first year of anti-TNF therapy, followed by slower but significant recovery
over the subsequent four years.
PMID- 25110679
TI - Evaluation of macular retinal ganglion cell-inner plexiform layer thickness after
vitrectomy with internal limiting membrane peeling for idiopathic macular holes.
AB - PURPOSE: To evaluate macular retinal ganglion cell-inner plexiform layer (GCIPL)
thickness changes after Brilliant Blue G-assisted internal limiting membrane
peeling for idiopathic macular hole repair using a high-resolution spectral
domain optical coherence tomography (SD-OCT). METHODS: 32 eyes from 32 patients
with idiopathic macular holes who underwent vitrectomy with internal limiting
membrane peeling between January 2011 and July 2012 were retrospectively
analyzed. GCIPL thickness was measured before surgery, and at one month and at
six months after surgery. Values obtained from automated and semimanual SD-OCT
segmentation analysis were compared (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin,
CA). RESULTS: No significant differences were found between average GCIPL
thickness values between preoperative and postoperative analysis. However,
statistical significant differences were found in GCIPL thickness at the temporal
macular quadrants at six months after surgery. Quality measurement analysis
performed by automated segmentation revealed a significant number of segmentation
errors. Semimanual segmentation slightly improved the quality of the results.
CONCLUSION: SD-OCT analysis of GCIPL thickness found a significant reduction at
the temporal macular quadrants at 6 months after Brilliant Blue G-assisted
internal limiting membrane peeling for idiopathic macular hole.
PMID- 25110680
TI - Specific growth rate determines the sensitivity of Escherichia coli to lactic
acid stress: implications for predictive microbiology.
AB - This study tested the hypothesis that sensitivity of Escherichia coli to lactic
acid at concentrations relevant for fermented sausages (pH 4.6, 150 mM lactic
acid, aw = 0.92, temperature = 20 or 27 degrees C) increases with increasing
growth rate. For E. coli strain 683 cultured in TSB in chemostat or batch,
subsequent inactivation rates when exposed to lactic acid stress increased with
increasing growth rate at harvest. A linear relationship between growth rate at
harvest and inactivation rate was found to describe both batch and chemostat
cultures. The maximum difference in T90, the estimated times for a one-log
reduction, was 10 hours between bacteria harvested during the first 3 hours of
batch culture, that is, at different growth rates. A 10-hour difference in T90
would correspond to measuring inactivation at 33 degrees C or 45 degrees C
instead of 37 degrees C based on relationships between temperature and
inactivation. At similar harvest growth rates, inactivation rates were lower for
bacteria cultured at 37 degrees C than at 15-20 degrees C. As demonstrated for E.
coli 683, culture conditions leading to variable growth rates may contribute to
variable lactic acid inactivation rates. Findings emphasize the use and reporting
of standardised culture conditions and can have implications for the
interpretation of data when developing inactivation models.
PMID- 25110681
TI - Healing efficacy of an EGF impregnated triple gel based wound dressing: in vitro
and in vivo studies.
AB - To accomplish an ideal wound healing process which promotes healthy tissue growth
with less scaring, a novel gel based topical drug delivery system composed of 3
different polymers chitosan, dextran sulfate, and polyvinylpyrrolidone K30 (CDP)
was prepared. The physicochemical properties of the prepared gels were
investigated in vitro. Gels showed a maximum swelling ratio of 50 +/- 1.95 times
of dried gel in PBS at pH 7.4. The swelling ratios increase in acidic and
alkaline pH to 55.3 +/- 1.75 and 65.5 +/- 2.42, respectively. In the rheological
test, prepared gels revealed viscoelastic properties and a small linear
viscoelastic region of 0.166%. In vivo wound healing promoting activities of CDP
gels containing 20 MUg/mL EGF were evaluated on surgically induced dermal wounds
in rats using pathologic examination. The application of CDP gel with
incorporated EGF significantly reduced the defect on the rat's skin and enhanced
epithelial healing compared with the topical application of the EGF-free CDP gel.
The results clearly substantiate the beneficial effects of the topical
application of CDP containing EGF in the acceleration of healthy wound healing
process with less scarring.
PMID- 25110682
TI - Induction of boosted immune response in mice by leptospiral surface proteins
expressed in fusion with DnaK.
AB - Leptospirosis is an important global disease of human and veterinary concern.
Caused by pathogenic Leptospira, the illness was recently classified as an
emerging infectious disease. Currently available veterinarian vaccines do not
induce long-term protection against infection and do not provide cross-protective
immunity. Several studies have suggested the use of DnaK as an antigen in vaccine
formulation, due to an exceptional degree of immunogenicity. We focused on four
surface proteins: rLIC10368 (Lsa21), rLIC10494, rLIC12690 (Lp95), and rLIC12730,
previously shown to be involved in host-pathogen interactions. Our goal was to
evaluate the immunogenicity of the proteins genetically fused with DnaK in animal
model. The chosen genes were amplified by PCR methodology and cloned into pAE, an
E. coli vector. The recombinant proteins were expressed alone or in fusion with
DnaK at the N-terminus. Our results demonstrate that leptospiral proteins fused
with DnaK have elicited an enhanced immune response in mice when compared to the
effect promoted by the individual proteins. The boosted immune effect was
demonstrated by the production of total IgG, lymphocyte proliferation, and
significant amounts of IL-10 in supernatant of splenocyte cell cultures. We
believe that this approach could be employed in vaccines to enhance presentation
of antigens of Leptospira to professional immune cells.
PMID- 25110683
TI - Potential use of halophytes to remediate saline soils.
AB - Salinity is one of the rising problems causing tremendous yield losses in many
regions of the world especially in arid and semiarid regions. To maximize crop
productivity, these areas should be brought under utilization where there are
options for removing salinity or using the salt-tolerant crops. Use of salt
tolerant crops does not remove the salt and hence halophytes that have capacity
to accumulate and exclude the salt can be an effective way. Methods for salt
removal include agronomic practices or phytoremediation. The first is cost- and
labor-intensive and needs some developmental strategies for implication; on the
contrary, the phytoremediation by halophyte is more suitable as it can be
executed very easily without those problems. Several halophyte species including
grasses, shrubs, and trees can remove the salt from different kinds of salt
affected problematic soils through salt excluding, excreting, or accumulating by
their morphological, anatomical, physiological adaptation in their organelle
level and cellular level. Exploiting halophytes for reducing salinity can be good
sources for meeting the basic needs of people in salt-affected areas as well.
This review focuses on the special adaptive features of halophytic plants under
saline condition and the possible ways to utilize these plants to remediate
salinity.
PMID- 25110684
TI - Feasibility study of a hand guided robotic drill for cochleostomy.
AB - The concept of a hand guided robotic drill has been inspired by an automated, arm
supported robotic drill recently applied in clinical practice to produce
cochleostomies without penetrating the endosteum ready for inserting cochlear
electrodes. The smart tactile sensing scheme within the drill enables precise
control of the state of interaction between tissues and tools in real-time. This
paper reports development studies of the hand guided robotic drill where the same
consistent outcomes, augmentation of surgeon control and skill, and similar
reduction of induced disturbances on the hearing organ are achieved. The device
operates with differing presentation of tissues resulting from variation in
anatomy and demonstrates the ability to control or avoid penetration of tissue
layers as required and to respond to intended rather than involuntary motion of
the surgeon operator. The advantage of hand guided over an arm supported system
is that it offers flexibility in adjusting the drilling trajectory. This can be
important to initiate cutting on a hard convex tissue surface without slipping
and then to proceed on the desired trajectory after cutting has commenced. The
results for trials on phantoms show that drill unit compliance is an important
factor in the design.
PMID- 25110686
TI - Dehydroabietic acid derivative QC2 induces oncosis in hepatocellular carcinoma
cells.
AB - AIM: Rosin, the traditional Chinese medicine, is reported to be able to inhibit
skin cancer cell lines. In this report, we investigate the inhibitory effect
against HCC cells of QC2, the derivative of rosin's main components
dehydroabietic acid. METHODS: MTT assay was used to determine the cytotoxicity of
QC2. Morphological changes were observed by time-lapse microscopy and
transmission electron microscopy and the cytoskeleton changes were observed by
laser-scanning confocal microscopy. Cytomembrane integrity and organelles damage
were confirmed by detection of the reactive oxygen (ROS), lactate dehydrogenase
(LDH), and mitochondrial membrane potential (Deltapsim). The underlying mechanism
was manifested by Western blotting. The oncotic cell death was further confirmed
by detection of oncosis related protein calpain. RESULTS: Swelling cell type and
destroyed cytoskeleton were observed in QC2-treated HCC cells. Organelle damage
was visualized by transmission electron microscopy. The detection of ROS
accumulation, increased LDH release, and decreased ATP and Deltapsim confirmed
the cell death. The oncotic related protein calpain was found to increase time
dependently in QC2-treated HCC cells, while its inhibitor PD150606 attenuated the
cytotoxicity. CONCLUSIONS: Dehydroabietic acid derivative QC2 activated oncosis
related protein calpain to induce the damage of cytomembrane and organelles which
finally lead to oncosis in HCC cells.
PMID- 25110687
TI - Characteristics and prediction of RNA structure.
AB - RNA secondary structures with pseudoknots are often predicted by minimizing free
energy, which is NP-hard. Most RNAs fold during transcription from DNA into RNA
through a hierarchical pathway wherein secondary structures form prior to
tertiary structures. Real RNA secondary structures often have local instead of
global optimization because of kinetic reasons. The performance of RNA structure
prediction may be improved by considering dynamic and hierarchical folding
mechanisms. This study is a novel report on RNA folding that accords with the
golden mean characteristic based on the statistical analysis of the real RNA
secondary structures of all 480 sequences from RNA STRAND, which are validated by
NMR or X-ray. The length ratios of domains in these sequences are approximately
0.382L, 0.5L, 0.618L, and L, where L is the sequence length. These points are
just the important golden sections of sequence. With this characteristic, an
algorithm is designed to predict RNA hierarchical structures and simulate RNA
folding by dynamically folding RNA structures according to the above golden
section points. The sensitivity and number of predicted pseudoknots of our
algorithm are better than those of the Mfold, HotKnots, McQfold, ProbKnot, and
Lhw-Zhu algorithms. Experimental results reflect the folding rules of RNA from a
new angle that is close to natural folding.
PMID- 25110685
TI - New insight into adiponectin role in obesity and obesity-related diseases.
AB - Obesity is a major health problem strongly increasing the risk for various severe
related complications such as metabolic syndrome, cardiovascular diseases,
respiratory disorders, diabetic retinopathy, and cancer. Adipose tissue is an
endocrine organ that produces biologically active molecules defined
"adipocytokines," protein hormones with pleiotropic functions involved in the
regulation of energy metabolism as well as in appetite, insulin sensitivity,
inflammation, atherosclerosis, cell proliferation, and so forth. In obesity, fat
accumulation causes dysregulation of adipokine production that strongly
contributes to the onset of obesity-related diseases. Several advances have been
made in the treatment and prevention of obesity but current medical therapies are
often unsuccessful even in compliant patients. Among the adipokines, adiponectin
shows protective activity in various processes such as energy metabolism,
inflammation, and cell proliferation. In this review, we will focus on the
current knowledge regarding the protective properties of adiponectin and its
receptors, AdipoRs ("adiponectin system"), on metabolic complications in obesity
and obesity-related diseases. Adiponectin, exhibiting antihyperglycemic,
antiatherogenic, and anti-inflammatory properties, could have important clinical
benefits in terms of development of therapies for the prevention and/or for the
treatment of obesity and obesity-related diseases.
PMID- 25110688
TI - Expression profiling of abiotic stress-inducible genes in response to multiple
stresses in rice (Oryza sativa L.) varieties with contrasting level of stress
tolerance.
AB - The present study considered transcriptional profiles and protein expression
analyses from shoot and/or root tissues under three abiotic stress conditions,
namely, salinity, dehydration, and cold, as well as following exogenous abscisic
acid treatment, at different time points of stress exposure in three indica rice
varieties, IR-29 (salt sensitive), Pokkali, and Nonabokra (both salt tolerant).
The candidate genes chosen for expression studies were HKT-1, SOS-3, NHX-1,
SAPK5, SAPK7, NAC-1, Rab16A, OSBZ8, DREBP2, CRT/DREBP, WRKY24, and WRKY71, along
with the candidate proteins OSBZ8, SAMDC, and GST. Gene expression profile
revealed considerable differences between the salt-sensitive and salt-tolerant
rice varieties, as the expression in the latter was higher even at the
constitutive level, whereas it was inducible only by corresponding stress signals
in IR-29. Whether in roots or shoots, the transcriptional responses to different
stressors peaked following 24 h of stress/ABA exposure, and the transcript levels
enhanced gradually with the period of exposure. The generality of stress
responses at the transcriptional level was therefore time dependent. Heat map
data also showed differential transcript abundance in the three varieties,
correlating the observation with transcript profiling. In silico analysis of the
upstream regions of all the genes represented the existence of conserved sequence
motifs in single or multiple copies that are indispensable to abiotic stress
response. Overall, the transcriptome and proteome analysis undertaken in the
present study indicated that genes/proteins conferring tolerance, belonging to
different functional classes, were overrepresented, thus providing novel insight
into the functional basis of multiple stress tolerance in indica rice varieties.
The present work will pave the way in future to select gene(s) for
overexpression, so as to generate broad spectrum resistance to multiple stresses
simultaneously.
PMID- 25110689
TI - Production of conjugated linoleic and conjugated alpha-linolenic acid in a
reconstituted skim milk-based medium by bifidobacterial strains isolated from
human breast milk.
AB - Eight bifidobacterial strains isolated from human breast milk have been tested
for their abilities to convert linoleic acid (LA) and alpha-linolenic acid (LNA)
to conjugated linoleic acid (CLA) and conjugated alpha-linolenic acid (CLNA),
respectively. These bioactive lipids display important properties that may
contribute to the maintenance and improvement human health. Three selected
Bifidobacterium breve strains produced CLA from LA and CLNA from LNA in MRS (160
170 and 210-230 MUg mL(-1), resp.) and, also, in reconstituted skim milk (75-95
and 210-244 MUg mL(-1), resp.). These bifidobacterial strains were also able to
simultaneously produce both CLA (90-105 MUg mL(-1)) and CLNA (290-320 MUg mL(-1))
in reconstituted skim milk. Globally, our findings suggest that these
bifidobacterial strains are potential candidates for the design of new fermented
dairy products naturally containing very high concentrations of these bioactive
lipids. To our knowledge, this is the first study describing CLNA production and
coproduction of CLA and CLNA by Bifidobacterium breve strains isolated from human
milk in reconstituted skim milk.
PMID- 25110690
TI - Investigation of the interaction between patulin and human serum albumin by a
spectroscopic method, atomic force microscopy, and molecular modeling.
AB - The interaction of patulin with human serum albumin (HSA) was studied in vitro
under normal physiological conditions. The study was performed using
fluorescence, ultraviolet-visible spectroscopy (UV-Vis), circular dichroism (CD),
atomic force microscopy (AFM), and molecular modeling techniques. The quenching
mechanism was investigated using the association constants, the number of binding
sites, and basic thermodynamic parameters. A dynamic quenching mechanism occurred
between HSA and patulin, and the binding constants (K) were 2.60 * 10(4), 4.59 *
10(4), and 7.01 * 10(4) M(-1) at 288, 300, and 310 K, respectively. Based on
fluorescence resonance energy transfer, the distance between the HSA and patulin
was determined to be 2.847 nm. The DeltaG (0), DeltaH (0), and DeltaS (0) values
across various temperatures indicated that hydrophobic interaction was the
predominant binding force. The UV-Vis and CD results confirmed that the secondary
structure of HSA was altered in the presence of patulin. The AFM results revealed
that the individual HSA molecule dimensions were larger after interaction with
patulin. In addition, molecular modeling showed that the patulin-HSA complex was
stabilized by hydrophobic and hydrogen bond forces. The study results suggested
that a weak intermolecular interaction occurred between patulin and HSA. Overall,
the results are potentially useful for elucidating the toxigenicity of patulin
when it is combined with the biomolecular function effect, transmembrane
transport, toxicological, testing and other experiments.
PMID- 25110691
TI - Advanced user interfaces for neurorehabilitation.
PMID- 25110693
TI - Effect of duplicate genes on mouse genetic robustness: an update.
AB - In contrast to S. cerevisiae and C. elegans, analyses based on the current
knockout (KO) mouse phenotypes led to the conclusion that duplicate genes had
almost no role in mouse genetic robustness. It has been suggested that the bias
of mouse KO database toward ancient duplicates may possibly cause this knockout
duplicate puzzle, that is, a very similar proportion of essential genes (PE)
between duplicate genes and singletons. In this paper, we conducted an extensive
and careful analysis for the mouse KO phenotype data and corroborated a strong
effect of duplicate genes on mouse genetics robustness. Moreover, the effect of
duplicate genes on mouse genetic robustness is duplication-age dependent, which
holds after ruling out the potential confounding effect from coding-sequence
conservation, protein-protein connectivity, functional bias, or the bias of
duplicates generated by whole genome duplication (WGD). Our findings suggest that
two factors, the sampling bias toward ancient duplicates and very ancient
duplicates with a proportion of essential genes higher than that of singletons,
have caused the mouse knockout duplicate puzzle; meanwhile, the effect of genetic
buffering may be correlated with sequence conservation as well as protein-protein
interactivity.
PMID- 25110694
TI - Emotion recognition pattern in adolescent boys with attention
deficit/hyperactivity disorder.
AB - BACKGROUND: Social and emotional deficits were recently considered as inherent
features of individuals with attention-deficit hyperactivity disorder (ADHD), but
only sporadic literature data exist on emotion recognition in adolescents with
ADHD. The aim of the present study was to establish emotion recognition profile
in adolescent boys with ADHD in comparison with control adolescents. METHODS:
Forty-four adolescent boys (13-16 years) participated in the study after informed
consent; 22 boys had a clinical diagnosis of ADHD, while data were also assessed
from 22 adolescent control boys matched for age and Raven IQ. Parent- and self
reported behavioral characteristics were assessed by the means of the Strengths
and Difficulties Questionnaire. The recognition of six basic emotions was
evaluated by the "Facial Expressions of Emotion-Stimuli and Tests." RESULTS:
Compared to controls, adolescents with ADHD were more sensitive in the
recognition of disgust and, worse in the recognition of fear and showed a
tendency for impaired recognition of sadness. Hyperactivity measures showed an
inverse correlation with fear recognition. CONCLUSION: Our data suggest that
adolescent boys with ADHD have alterations in the recognition of specific
emotions.
PMID- 25110695
TI - Prolonged sleep deprivation and continuous exercise: effects on melatonin,
tympanic temperature, and cognitive function.
AB - The purpose of this study was to examine tympanic temperature, melatonin, and
cognitive function during a 36-hour endurance event. Nine male and three female
participants took part in a 36-hour sustained endurance event without sleep (N =
12, mean age = 31.8 +/- 5.0 yrs). Participants were stopped for data collection
at checkpoints throughout the 36-hour event. Tympanic temperature was assessed, a
psychomotor vigilance test (PVT) was administered, and saliva samples were
collected. Salivary melatonin was determined via immunoassay. During the 36 hours
of competition, melatonin levels were negatively correlated with the day of the
race (rs = -0.277, P = 0.039) and positively associated with nighttime (rs =
0.316, P = 0.021). Significant main effects of tympanic temperature (P < 0.001),
day of the competition (P = 0.018), and a tympanic temperature * day of
competition interaction (P < 0.001) were used to predict minor lapses in
attention. No associations between melatonin levels and cognitive function were
observed (P > 0.05). During the event tympanic temperature declined and was
associated with an increase in lapses in attention. With sustained endurance
events becoming more popular future research is warranted to evaluate the
physiological impact of participation.
PMID- 25110696
TI - Connexin 43 expression on peripheral blood eosinophils: role of gap junctions in
transendothelial migration.
AB - Eosinophils circulate in the blood and are recruited in tissues during allergic
inflammation. Gap junctions mediate direct communication between adjacent cells
and may represent a new way of communication between immune cells distinct from
communication through cytokines and chemokines. We characterized the expression
of connexin (Cx)43 by eosinophils isolated from atopic individuals using RT-PCR,
Western blotting, and confocal microscopy and studied the biological functions of
gap junctions on eosinophils. The formation of functional gap junctions was
evaluated measuring dye transfer using flow cytometry. The role of gap junctions
on eosinophil transendothelial migration was studied using the inhibitor 18-a
glycyrrhetinic acid. Peripheral blood eosinophils express Cx43 mRNA and protein.
Cx43 is localized not only in the cytoplasm but also on the plasma membrane. The
membrane impermeable dye BCECF transferred from eosinophils to epithelial or
endothelial cells following coculture in a dose and time dependent fashion. The
gap junction inhibitors 18-a-glycyrrhetinic acid and octanol did not have a
significant effect on dye transfer but reduced dye exit from eosinophils. The gap
junction inhibitor 18-a-glycyrrhetinic acid inhibited eosinophil transendothelial
migration in a dose dependent manner. Thus, eosinophils from atopic individuals
express Cx43 constitutively and Cx43 may play an important role in eosinophil
transendothelial migration and function in sites of inflammation.
PMID- 25110697
TI - Magnetic resonance spectroscopy in the diagnosis of dementia with Lewy bodies.
AB - Dementia with Lewy bodies (DLB) is considered to be the second most frequent
primary degenerative dementing illness after Alzheimer's disease (AD). DLB,
together with Parkinson's disease (PD), Parkinson's disease with dementia (PDD)
belong to alpha-synucleinopathies--a group of neurodegenerative diseases
associated with pathological accumulation of the alpha-synuclein protein.
Dementia due to PD and DLB shares clinical symptoms and neuropsychological
profiles. Moreover, the core features and additional clinical signs and symptoms
for these two very similar diseases are largely the same. Neuroimaging seems to
be a promising method in differential diagnosis of dementia studies. The
development of imaging methods or other objective measures to supplement clinical
criteria for DLB is needed and a method which would accurately facilitate
diagnosis of DLB prior to death is still being searched. Proton magnetic
resonance spectroscopy ((1)H-MRS) provides a noninvasive method of assessing an
in vivo biochemistry of brain tissue. This review summarizes the main results
obtained from the application of neuroimaging techniques in DLB cases focusing on
(1)H-MRS.
PMID- 25110698
TI - Upper limb posture estimation in robotic and virtual reality-based
rehabilitation.
AB - New motor rehabilitation therapies include virtual reality (VR) and robotic
technologies. In limb rehabilitation, limb posture is required to (1) provide a
limb realistic representation in VR games and (2) assess the patient improvement.
When exoskeleton devices are used in the therapy, the measurements of their joint
angles cannot be directly used to represent the posture of the patient limb,
since the human and exoskeleton kinematic models differ. In response to this
shortcoming, we propose a method to estimate the posture of the human limb
attached to the exoskeleton. We use the exoskeleton joint angles measurements and
the constraints of the exoskeleton on the limb to estimate the human limb joints
angles. This paper presents (a) the mathematical formulation and solution to the
problem, (b) the implementation of the proposed solution on a commercial
exoskeleton system for the upper limb rehabilitation, (c) its integration into a
rehabilitation VR game platform, and (d) the quantitative assessment of the
method during elbow and wrist analytic training. Results show that this method
properly estimates the limb posture to (i) animate avatars that represent the
patient in VR games and (ii) obtain kinematic data for the patient assessment
during elbow and wrist analytic rehabilitation.
PMID- 25110699
TI - Cementless fixation of osteoporotic VCFs using titanium mesh implants (OsseoFix):
preliminary results.
AB - INTRODUCTION: Vertebral compression fractures (VCFs) affect 20% of people over
the age of 70 with increasing incidence. Kypho-/vertebroplasty as standard
operative procedures are associated with limitations like cement leakage, limited
reduction capabilities, and risk for adjacent fractures. To address these
shortcomings, we introduce a new minimal invasive cementless VCF fixation
technique. METHODS: Four patients (72.3 years, range 70-76) with VCFs type
AO/Muller A1.3 and concomitant osteoporosis were treated by minimal invasive
transpedicular placement of two intervertebral mesh cages for fracture reduction
and maintenance. Follow-up included functional/radiological assessment and
clinical scores and averaged 27.7 months (24-28). RESULTS: Endplate reduction was
achieved in all cases (mean surgery time: 28.5 minutes). Kyphotic (KA) and Cobb
angle revealed considerable improvements postoperatively (KA 14.5 degrees to
10.7 degrees /Cobb 10.1 degrees to 8.3 degrees ). Slight loss of vertebral
reduction (KA: 12.6 degrees ) and segment rekyphosis (Cobb: 10.7 degrees ) were
observed for final follow-up. Pain improved from 8.8 to 2.8 (visual analogue
scale). All cases showed signs of bony healing. No perioperative complications
and no adjacent fractures occurred. CONCLUSION: Preliminary results in a small,
selected patient collective indicate the ability of bony healing for osteoporotic
VCFs. Cementless fixation using intravertebral titanium mesh cages revealed
substantial pain relief, adequate reduction, and reduction maintenance without
complications. Trial registration number is DRKS00005657, German Clinical Trials
Register (DKRS).
PMID- 25110692
TI - The role of chemoattractant receptors in shaping the tumor microenvironment.
AB - Chemoattractant receptors are a family of seven transmembrane G protein coupled
receptors (GPCRs) initially found to mediate the chemotaxis and activation of
immune cells. During the past decades, the functions of these GPCRs have been
discovered to not only regulate leukocyte trafficking and promote immune
responses, but also play important roles in homeostasis, development,
angiogenesis, and tumor progression. Accumulating evidence indicates that
chemoattractant GPCRs and their ligands promote the progression of malignant
tumors based on their capacity to orchestrate the infiltration of the tumor
microenvironment by immune cells, endothelial cells, fibroblasts, and mesenchymal
cells. This facilitates the interaction of tumor cells with host cells, tumor
cells with tumor cells, and host cells with host cells to provide a basis for the
expansion of established tumors and development of distant metastasis. In
addition, many malignant tumors of the nonhematopoietic origin express multiple
chemoattractant GPCRs that increase the invasiveness and metastasis of tumor
cells. Therefore, GPCRs and their ligands constitute targets for the development
of novel antitumor therapeutics.
PMID- 25110701
TI - Significance of image guidance to clinical outcomes for localized prostate
cancer.
AB - PURPOSE: To compare toxicity profiles and biochemical tumor control outcomes
between patients treated with image-guided intensity-modulated radiotherapy (IG
IMRT) and non-IGRT intensity-modulated radiotherapy (IMRT) for clinically
localized prostate cancer. MATERIALS AND METHODS: Between 2009 and 2012, 65
patients with localized prostate cancer were treated with IG-IMRT. This group of
patients was retrospectively compared with a similar cohort of 62 patients who
were treated between 2004 and 2009 with IMRT to the same dose without image
guidance. RESULTS: The median follow-up time was 4.8 years. The rectal volume
receiving >=40 and >=70 Gy was significantly lower in the IG-IMRT group. Grade 2
and higher acute and late GI and GU toxicity rates were lower in IG-IMRT group,
but there was no statistical difference. No significant improvement in
biochemical control at 5 years was observed in two groups. In a Cox regression
analysis identifying predictors for PSA relapse-free survival, only
preradiotherapy PSA was significantly associated with biochemical control; IG
IMRT was not a statistically significant indicator. CONCLUSIONS: The use of image
guidance in the radiation of prostate cancer at our institute did not show
significant reduction in the rates of GI and GU toxicity and did not improve the
biochemical control compared with IMRT.
PMID- 25110700
TI - The harmful effects of subarachnoid hemorrhage on extracerebral organs.
AB - Subarachnoid hemorrhage (SAH) is a devastating neurological disorder. Patients
with aneurysmal SAH develop secondary complications that are important causes of
morbidity and mortality. Aside from secondary neurological injuries, SAH has been
associated with nonneurologic medical complications, such as neurocardiogenic
injury, neurogenic pulmonary edema, hyperglycemia, and electrolyte imbalance, of
which cardiac and pulmonary complications are most common. The related mechanisms
include activation of the sympathetic nervous system, release of catecholamines
and other hormones, and inflammatory responses. Extracerebral complications are
directly related to the severity of SAH-induced brain injury and indicate the
clinical outcome in patients. This review provides an overview of the
extracerebral complications after SAH. We also aim to describe the
manifestations, underlying mechanisms, and the effects of those extracerebral
complications on outcome following SAH.
PMID- 25110703
TI - Current evidence regarding prophylactic antibiotics in head and neck and
maxillofacial surgery.
AB - Antibiotic prophylaxis is commonly used to decrease the rate of infections in
head and neck surgery. The aim of this paper is to present the available evidence
regarding the application of antibiotic prophylaxis in surgical procedures of the
head and neck region in healthy patients. A systemic literature review based on
Medline and Embase databases was performed. All reviews and meta-analyses based
on RCTs in English from 2000 to 2013 were included. Eight out of 532 studies
fulfilled all requirements. Within those, only seven different operative
procedures were analyzed. Evidence exists for the beneficial use of prophylactic
antibiotics for tympanostomy, orthognathic surgery, and operative tooth
extractions. Unfortunately, little high-level evidence exists regarding the use
of prophylactic antibiotics in head and neck surgery. In numerous cases, no clear
benefit of antibiotic prophylaxis has been shown, particularly considering their
potential adverse side effects. Antibiotics are often given unnecessarily and are
administered too late and for too long. Furthermore, little research has been
performed on the large number of routine cases in the above-mentioned areas of
specialization within the last few years, although questions arising with respect
to the treatment of high-risk patients or of specific infections are discussed on
a broad base.
PMID- 25110702
TI - Immunocontraceptives: new approaches to fertility control.
AB - The rapidly increasing global population has bowed the attention of family
planning and associated reproductive health programmes in the direction of
providing a safe and reliable method which can be used to limit family size. The
world population is estimated to exceed a phenomenal 10 billion by the year 2050
A.D., thus presenting a real jeopardy of overpopulation with severe implications
for the future. Despite the availability of contraceptive methods, there are over
one million elective abortions globally each year due to unintended pregnancies,
having devastating impact on reproductive health of women worldwide. This
highlights the need for the development of newer and improved contraceptive
methods. A novel contraceptive approach that is gaining substantial attention is
"immunocontraception" targeting gamete production, gamete outcome, or gamete
function. Amongst these, use of sperm antigens (gamete function) seems to be an
exciting and feasible approach. However, the variability of immune response and
time lag to attain titer among vaccinated individuals after active immunization
has highlighted the potential relevance of preformed antibodies in this league.
This review is an attempt to analyze the current status and progress of
immunocontraceptive approaches with respect to their establishment as a future
fertility control agent.
PMID- 25110704
TI - Neurobiological mechanisms of pelvic pain.
AB - Pelvic pain is a common condition which significantly deteriorates health-related
quality of life. The most commonly identified causes of pain in the pelvic region
are gynaecologic, urologic, gastrointestinal, neurological, and musculoskeletal.
However, in up to 33% of patients the source of this symptom is not identified,
frustrating both patients and health-care professionals. Pelvic pain may involve
both the somatic and visceral systems, making the differential diagnosing
challenging. This paper aimed to review the mechanisms involved in pelvic pain
perception by analyzing the neural plasticity and molecules which are involved in
these complex circuits.
PMID- 25110705
TI - Cisplatin-based chemotherapy versus cetuximab in concurrent chemoradiotherapy for
locally advanced head and neck cancer treatment.
AB - BACKGROUND AND PURPOSE: This study aimed to analyze survival, clinical responses,
compliance, and adverse effects in locally advanced head and neck cancer (LAHNC)
patients treated with split-dose cisplatin-based concurrent chemoradiation
therapy (SD-CCRT) or cetuximab with concurrent radiation therapy (BioRT).
MATERIALS AND METHODS: We retrospectively evaluated 170 LAHNC patients diagnosed
between January 1, 2009, and July 31, 2012: 116 received CCRT and 54 received
BioRT. RESULTS: Complete response rates were similar in the SD-CCRT and BioRT
groups (63.8% versus 59.3%; P = 0.807), and locoregional relapse rates were 18.1%
and 13.0%, respectively (P = 0.400). The 3-year relapse-free survival rate was
65.8% in the SD-CCRT group and 65.5% in the BioRT group, respectively (P =
0.647). The 3-year overall survival rate was 78.5% in the SD-CCRT group and 70.9%
in the BioRT group, respectively (P = 0.879). Hematologic side effects were
significantly more frequent in the SD-CCRT than in the BioRT group. Mucositis
frequency was similar. CONCLUSIONS: Primary SD-CCRT and BioRT both showed good
clinical response and survival. Hematologic toxicities were more frequent, but
tolerable, in the SD-CCRT group. Both groups showed good compliance.
PMID- 25110706
TI - Cardiac troponin T (TNNT2) mutations in chinese dilated cardiomyopathy patients.
AB - BACKGROUND: Dilated cardiomyopathy (DCM) is one of the leading causes of heart
failure with high morbidity and mortality. Although more than 40 genes have been
reported to cause DCM, the role of genetic testing in clinical practice is not
well defined. Mutations in the troponin T (TNNT2) gene represent an important
subset of known disease-causing mutations associated with DCM. Therefore, the aim
of the present study was to determine the genetic variations in TNNT2 and the
associations of those variations with DCM in Chinese patients. METHODS: An
approximately 4 kb fragment of the TNNT2 gene was isolated from 103 DCM patients
and 192 healthy controls and was analyzed by DNA sequence analysis for genetic
variations. RESULTS: A total of 6 TNNT2 mutations were identified in 99 patients,
including a G321T missense mutation (Leu84Phe) and 5 novel intronic mutations.
Alleles of two novel SNPs (c.192 + 353 C>A, OR = 0.095, 95% CI: 0.013-0.714, P =
0.022; c.192 + 463 G>A, OR = 0.090, 95% CI: 0.012-0.675, P = 0.019) and SNP
rs3729843 (OR = 1.889, 95% CI: 1.252-2.852; P = 0.002) were significantly
correlated with DCM. CONCLUSIONS: These results suggest that the missense
mutation (Leu84Phe) and two novel SNPs (c.192 + 353 C>A, c.192 + 463 G>A) in
TNNT2 gene might be associated with DCM in the Chinese population.
PMID- 25110707
TI - Acute and long-term effects of noise exposure on the neuronal spontaneous
activity in cochlear nucleus and inferior colliculus brain slices.
AB - Noise exposure leads to an immediate hearing loss and is followed by a long
lasting permanent threshold shift, accompanied by changes of cellular properties
within the central auditory pathway. Electrophysiological recordings have
demonstrated an upregulation of spontaneous neuronal activity. It is still
discussed if the observed effects are related to changes of peripheral input or
evoked within the central auditory system. The present study should describe the
intrinsic temporal patterns of single-unit activity upon noise-induced hearing
loss of the dorsal and ventral cochlear nucleus (DCN and VCN) and the inferior
colliculus (IC) in adult mouse brain slices. Recordings showed a slight, but
significant, elevation in spontaneous firing rates in DCN and VCN immediately
after noise trauma, whereas no differences were found in IC. One week
postexposure, neuronal responses remained unchanged compared to controls. At 14
days after noise trauma, intrinsic long-term hyperactivity in brain slices of the
DCN and the IC was detected for the first time. Therefore, increase in
spontaneous activity seems to develop within the period of two weeks, but not
before day 7. The results give insight into the complex temporal
neurophysiological alterations after noise trauma, leading to a better
understanding of central mechanisms in noise-induced hearing loss.
PMID- 25110708
TI - A review on the traditional Chinese medicinal herbs and formulae with
hypolipidemic effect.
AB - Hyperlipidemia, characterized by the abnormal blood lipid profiles, is one of the
dominant factors of many chronic diseases such as diabetes, obesity, and
cardiovascular diseases (CVD). For the low cost, effectiveness, and fewer side
effects, the popularity of using traditional Chinese medicine (TCM) to handle
hyperlipidemia is increasing and its role in health care has been recognized by
the public at large. Despite the importance of TCM herbs and formulations, there
is no comprehensive review summarizing their scientific findings on handling
hyperlipidemia. This review summarizes the recent experimental and clinical
results of nine representative single Chinese herbs and seven classic TCM
formulae that could improve lipid profiles so as to help understand and compare
their underlying mechanisms. Most of single herbs and formulae demonstrated the
improvement of hyperlipidemic conditions with multiple and diverse mechanisms of
actions similar to conventional Western drugs in spite of their mild side
effects. Due to increasing popularity of TCM, more extensive, well-designed
preclinical and clinical trials on the potential synergistic and adverse side
effects of herb-drug interactions as well as their mechanisms are warranted.
Hyperlipidemic patients should be warned about the potential risks of herb-drug
interactions, particularly those taking anticoagulants and antiplatelet drugs.
PMID- 25110710
TI - Amplification of the insulin-like growth factor 1 receptor gene is a rare event
in adrenocortical adenocarcinomas: searching for potential mechanisms of
overexpression.
AB - CONTEXT: IGF1R overexpression appears to be a prognostic biomarker of metastatic
pediatric adrenocortical tumors. However, the molecular mechanisms that are
implicated in its upregulation remain unknown. Aim. To investigate the potential
mechanisms involved in IGF1R overexpression. PATIENTS AND METHODS: We studied 64
adrenocortical tumors. IGF1R copy number variation was determined in all patients
using MLPA and confirmed using real time PCR. In a subgroup of 32 patients,
automatic sequencing was used to identify IGF1R allelic variants and the
expression of microRNAs involved in IGF1R regulation by real time PCR. RESULTS:
IGF1R amplification was detected in an adrenocortical carcinoma that was
diagnosed in a 46-year-old woman with Cushing's syndrome and virilization. IGF1R
overexpression was demonstrated in this case. In addition, gene amplification of
other loci was identified in this adrenocortical malignant tumor, but no IGF1R
copy number variation was evidenced in the remaining cases. Automatic sequencing
revealed three known polymorphisms but they did not correlate with its
expression. Expression of miR-100, miR-145, miR-375, and miR-126 did not
correlate with IGF1R expression. CONCLUSION: We demonstrated amplification and
overexpression of IGF1R gene in only one adrenocortical carcinoma, suggesting
that these combined events are uncommon. In addition, IGF1R polymorphisms and
abnormal microRNA expression did not correlate with IGF1R upregulation in
adrenocortical tumors.
PMID- 25110709
TI - The impact of simulated and real microgravity on bone cells and mesenchymal stem
cells.
AB - How microgravity affects the biology of human cells and the formation of 3D cell
cultures in real and simulated microgravity (r- and s-ug) is currently a hot
topic in biomedicine. In r- and s-ug, various cell types were found to form 3D
structures. This review will focus on the current knowledge of tissue engineering
in space and on Earth using systems such as the random positioning machine (RPM),
the 2D-clinostat, or the NASA-developed rotating wall vessel bioreactor (RWV) to
create tissue from bone, tumor, and mesenchymal stem cells. To understand the
development of 3D structures, in vitro experiments using s-ug devices can provide
valuable information about modulations in signal-transduction, cell adhesion, or
extracellular matrix induced by altered gravity conditions. These systems also
facilitate the analysis of the impact of growth factors, hormones, or drugs on
these tissue-like constructs. Progress has been made in bone tissue engineering
using the RWV, and multicellular tumor spheroids (MCTS), formed in both r- and s
ug, have been reported and were analyzed in depth. Currently, these MCTS are
available for drug testing and proteomic investigations. This review provides an
overview of the influence of ug on the aforementioned cells and an outlook for
future perspectives in tissue engineering.
PMID- 25110711
TI - The K-Cl cotransporter KCC3 as an independent prognostic factor in human
esophageal squamous cell carcinoma.
AB - The objectives of the present study were to investigate the role of K-Cl
cotransporter 3 (KCC3) in the regulation of cellular invasion and the
clinicopathological significance of its expression in esophageal squamous cell
carcinoma (ESCC). Immunohistochemical analysis performed on 70 primary tumor
samples obtained from ESCC patients showed that KCC3 was primarily found in the
cytoplasm of carcinoma cells. Although the expression of KCC3 in the main tumor
(MT) was related to several clinicopathological features, such as the pT and pN
categories, it had no prognostic impact. KCC3 expression scores were compared
between the MT and cancer nest (CN), and the survival rate of patients with a CN
> MT score was lower than that of patients with a CN <= MT score. In addition,
the survival rate of patients in whom KCC3 was expressed in the invasive front of
tumor was lower than that of the patients without it. Furthermore, multivariate
analysis demonstrated that the expression of KCC3 in the invasive front was one
of the most important independent prognostic factors. The depletion of KCC3 using
siRNAs inhibited cell migration and invasion in human ESCC cell lines. These
results suggest that the expression of KCC3 in ESCC may affect cellular invasion
and be related to a worse prognosis in patients with ESCC.
PMID- 25110712
TI - The tarsal bone test: a basic test of health sciences students' knowledge of
lower limb anatomy.
AB - OBJECTIVES: The aim of the present study was to design an easy-to-use tool, the
tarsal bone test (TBT), to provide a snapshot of podiatry students' basic
anatomical knowledge of the bones of the lower limb. METHODS: The study included
254 podiatry students from three different universities, 145 of them were first
year students and 109 were in their fourth and final years. The TBT was
administered without prior notice to the participants and was to be completed in
5 minutes. RESULTS: The results show that 97.2% of the subjects (n = 247)
correctly labelled all tarsal bones, while the other 2.8% (n = 7) incorrectly
labelled at least one bone, that was either the cuboid (7 times) or the navicular
(6 times). Although only one fourth-year student inaccurately identified one
bone, no significant differences in the distribution of the correct and incorrect
responses were found between first and fourth-year students. CONCLUSIONS: The TBT
seems to be a straightforward and easy-to-apply instrument, and provides an
objective view of the level of knowledge acquired at different stages of podiatry
studies.
PMID- 25110713
TI - Perinatal nitric oxide therapy prevents adverse effects of perinatal hypoxia on
the adult pulmonary circulation.
AB - Adverse events in utero are associated with the occurrence of chronic diseases in
adulthood. We previously demonstrated in mice that perinatal hypoxia resulted in
altered pulmonary circulation in adulthood, with a decreased endothelium
dependent relaxation of pulmonary arteries, associated with long-term alterations
in the nitric oxide (NO)/cyclic GMP pathway. The present study investigated
whether inhaled NO (iNO) administered simultaneously to perinatal hypoxia could
have potential beneficial effects on the adult pulmonary circulation. Indeed, iNO
is the therapy of choice in humans presenting neonatal pulmonary hypertension.
Long-term effects of neonatal iNO therapy on adult pulmonary circulation have not
yet been investigated. Pregnant mice were placed in hypoxia (13% O2) with
simultaneous administration of iNO 5 days before delivery until 5 days after
birth. Pups were then raised in normoxia until adulthood. Perinatal iNO
administration completely restored acetylcholine-induced relaxation, as well as
endothelial nitric oxide synthase protein content, in isolated pulmonary arteries
of adult mice born in hypoxia. Right ventricular hypertrophy observed in old mice
born in hypoxia compared to controls was also prevented by perinatal iNO
treatment. Therefore, simultaneous administration of iNO during perinatal hypoxic
exposure seems able to prevent adverse effects of perinatal hypoxia on the adult
pulmonary circulation.
PMID- 25110714
TI - Incorporating amino acids composition and functional domains for identifying
bacterial toxin proteins.
AB - Aside from pathogenesis, bacterial toxins also have been used for medical purpose
such as drugs for cancer and immune diseases. Correctly identifying bacterial
toxins and their types (endotoxins and exotoxins) has great impact on the cell
biology study and therapy development. However, experimental methods for
bacterial toxins identification are time-consuming and labor-intensive, implying
an urgent need for computational prediction. Thus, we are motivated to develop a
method for computational identification of bacterial toxins based on amino acid
sequences and functional domain information. In this study, a nonredundant
dataset of 167 bacterial toxins including 77 exotoxins and 90 endotoxins is
adopted to learn the predictive model by using support vector machines (SVMs).
The cross-validation evaluation shows that the SVM models trained with amino
acids and dipeptides composition could yield an accuracy of 96.07% and 92.50%,
respectively. For discriminating endotoxins from exotoxins, the SVM models
trained with amino acids and dipeptides composition have achieved an accuracy of
95.71% and 92.86%, respectively. After incorporating functional domain
information, the predictive performance is further improved. The proposed method
has been demonstrated to be able to more effectively identify and classify
bacterial toxins than the other two features on independent dataset, which may
aid in bacterial biomedical development.
PMID- 25110715
TI - Antioxidant properties of mushroom mycelia obtained by batch cultivation and
tocopherol content affected by extraction procedures.
AB - The determination of the antioxidant potential of lyophilized mushroom mycelia
from 5 strains of the species Pleurotus ostreatus and Coprinus comatus (obtained
by submerged cultivation in batch system) was analyzed as ethanolic extracts by
evaluating ABTS and the hydroxyl scavenging activity, FRAP method, the chelating
capacity, the inhibition of human erythrocyte hemolysis, and the inhibition of
xanthine oxidase activity. The main compounds present in all extracts were
determined by HPLC chromatography. Overall, results demonstrated that the
biologically active substances content is modulated by the extraction method
used. The most beneficial extract, characterized by determining the EC50 value,
was that of C. comatus M8102, followed by P. ostreatus PQMZ91109. Significant
amount of alpha-tocopherol (179.51 +/- 1.51 mg/100 g extract) was determined as
well as flavones such as rutin and apigenin. In the P. ostreatus PQMZ91109
extract, 4.8 +/- 0.05 mg/100 g extract of tocopherol acetate known to play a
significant role as an antioxidant in skin protection against oxidative stress
generated by UV rays was determined. The various correlations (r (2) = 0.7665
0.9426 for tocopherol content) assessed and the composition of extracts in
fluidized bed from the mycelia of the tested species depicted a significant
pharmacological potential as well as the possibility of usage in the development
of new functional products.
PMID- 25110716
TI - Influence of thread pitch, helix angle, and compactness on micromotion of
immediately loaded implants in three types of bone quality: a three-dimensional
finite element analysis.
AB - This study investigated the influence of thread pitch, helix angle, and
compactness on micromotion in immediately loaded implants in bone of varying
density (D2, D3, and D4). Five models of the three-dimensional finite element
(0.8 mm pitch, 1.6 mm pitch, 2.4 mm pitch, double-threaded, and triple-threaded
implants) in three types of bone were created using Pro/E, Hypermesh, and ABAQUS
software. The study had three groups: Group 1, different pitches (Pitch Group);
Group 2, same compactness but different helix angles (Angle Group); and Group 3,
same helix angle but different compactness (Compact Group). Implant micromotion
was assessed as the comprehensive relative displacement. We found that vertical
relative displacement was affected by thread pitch, helix angle, and compactness.
Under vertical loading, displacement was positively correlated with thread pitch
and helix angle but negatively with compactness. Under horizontal loading in D2,
the influence of pitch, helix angle, and compactness on implant stability was
limited; however, in D3 and D4, the influence of pitch, helix angle, and
compactness on implant stability is increased. The additional evidence was
provided that trabecular bone density has less effect on implant micromotion than
cortical bone thickness. Bone type amplifies the influence of thread pattern on
displacement.
PMID- 25110718
TI - Operational Definitions of Sexual Orientation and Estimates of Adolescent Health
Risk Behaviors.
AB - PURPOSE: Increasing attention to the health of lesbian, gay, and bisexual (LGB)
populations comes with requisite circumspection about measuring sexual
orientation in surveys. However, operationalizing these variables also requires
considerable thought. This research sought to document the consequences of
different operational definitions of sexual orientation by examining variation in
health risk behaviors. METHODS: Using Massachusetts Youth Risk Behavior Survey
data, we examined how operational definitions of sexual behavior and sexual
identity influenced differences among three health behaviors known to disparately
affect LGB populations: smoking, suicide risk, and methamphetamine use. Sexual
behavior and sexual identity were also examined together to explore if they
captured unique sources of variability in behavior. RESULTS: Estimates of health
disparities changed as a result of using either sexual behavior or sexual
identity. Youth who reported their sexual identity as "not sure" also had
increased odds of health risk behavior. Disaggregating bisexual identity and
behavior from same-sex identity and behavior frequently resulted in the
attenuation or elimination of health disparities that would have otherwise been
attributable to exclusively same-sex sexual minorities. Finally, sexual behavior
and sexual identity explained unique and significant sources of variability in
all three health behaviors. CONCLUSION: Researchers using different operational
definitions of sexual orientation could draw different conclusions, even when
analyzing the same data, depending upon how they chose to represent sexual
orientation in analyses. We discuss implications that these manipulations have on
data interpretation and provide specific recommendations for best-practices when
analyzing sexual orientation data collected from adolescent populations.
PMID- 25110719
TI - Utility of Diagnostic Imaging in the Diagnosis and Management of Schistosomiasis.
AB - Diagnosis of schistosomiasis is made by demonstration of the parasite ova in
stools, urine,and biopsy specimens from affected organs, or presence of
antibodies to the different stages of the parasite or antigens circulating in
body fluids by serologic techniques. DNA of schistosomes can now also be detected
in serum and stool specimens by molecular technique.However, these tests are
unable to determine the severity of target organ pathology and resultant
complications. Accurate assessment of schistosome-induced morbidities is now made
with the use of imaging techniques like ultrasound (US), computed tomography
(CT), and magnetic resonance imaging (MRI). US has made major contributions in
the diagnosis of hepatosplenic and urinary form of disease. This imaging method
provides real time results, is portable (can be carried to the bed side and the
field) and is lower in cost than other imaging techniques. Typical findings in
hepatosplenic schistosomiasis by US include: hyperechoic fibrotic bands along the
portal vessels (Symmer's fibrosis), reduction in the size of the right lobe,
hypertrophy of the left lobe, splenomegaly, and ascites. More advanced ultrasound
equipment like the colour Doppler ultrasound can characterize portal vein
perfusion, a procedure that is critical for the prediction of disease prognosis
and for treatment options for complicated portal hypertension. Although CT and
MRI are more expensive, are hospital based, and require highly additional
specially-trained personnel, they provide more accurate description of the
pathology, not only in hepatosplenic and urinary forms of schistosomiasis, but
also in the diagnosis of ectopic forms of the disease,particularly involving
thebrain and spinal cord. MRI demonstrates better tissue differentiation and lack
of exposure to ionizing radiation compared with CT.
PMID- 25110717
TI - TGF- beta: an important mediator of allergic disease and a molecule with dual
activity in cancer development.
AB - The transforming growth factor- beta (TGF- beta ) superfamily is a family of
structurally related proteins that includes TGF- beta , activins/inhibins, and
bone morphogenic proteins (BMPs). Members of the TGF- beta superfamily regulate
cellular functions such as proliferation, apoptosis, differentiation, and
migration and thus play key roles in organismal development. TGF- beta is
involved in several human diseases, including autoimmune disorders and vascular
diseases. Activation of the TGF- beta receptor induces phosphorylation of
serine/threonine residues and triggers phosphorylation of intracellular effectors
(Smads). Once activated, Smad proteins translocate to the nucleus and induce
transcription of their target genes, regulating various processes and cellular
functions. Recently, there has been an attempt to correlate the effect of TGF-
beta with various pathological entities such as allergic diseases and cancer,
yielding a new area of research known as "allergooncology," which investigates
the mechanisms by which allergic diseases may influence the progression of
certain cancers. This knowledge could generate new therapeutic strategies aimed
at correcting the pathologies in which TGF- beta is involved. Here, we review
recent studies that suggest an important role for TGF- beta in both allergic
disease and cancer progression.
PMID- 25110720
TI - Infections and inflammation in prostate cancer.
AB - The frequent observation of both acute and chronic inflammation of unknown
stimulus in the adult prostate has motivated a large body of research aimed at
identifying potential infectious agents that may elicit prostatic inflammation.
The overarching hypothesis is that infection-induced inflammation may be
associated with prostate cancer development or progression, as inflammation is
known to serve as an "enabling characteristic" of cancer. With recent advances in
molecular techniques for microorganism identification, a panoply of
microorganisms has been scrutinized in prostate tissues and in relation to
prostate carcinogenesis. The aim of this review is to summarize the current
literature on the evidence for infectious agents as a contributing factor to
prostatic inflammation and prostate cancer, and to highlight recent literature
suggesting an infectious etiology to the biogenesis of prostatic corpora amylacea
and on the development of mouse models of prostatic infections.
PMID- 25110722
TI - Facilitative and inhibitory effect of litter on seedling emergence and early
growth of six herbaceous species in an early successional old field ecosystem.
AB - In the current study, a field experiment was conducted to examine effects of
litter on seedling emergence and early growth of four dominant weed species from
the early successional stages of old field ecosystem and two perennial grassland
species in late successional stages. Our results showed that increased litter
cover decreased soil temperature and temperature variability over time and
improved soil moisture status. Surface soil electrical conductivity increased as
litter increased. The increased litter delayed seedling emergence time and rate.
The emergence percentage of seedlings and establishment success rate firstly
increased then decreased as litter cover increased. When litter biomass was below
600 g m(-2), litter increased seedlings emergence and establishment success in
all species. With litter increasing, the basal diameter of seedling decreased,
but seedling height increased. Increasing amounts of litter tended to increase
seedling dry weight and stem leaf ratio. Different species responded differently
to the increase of litter. Puccinellia tenuiflora and Chloris virgata will
acquire more emergence benefits under high litter amount. It is predicted that
Chloris virgata will dominate further in this natural succession old field
ecosystem with litter accumulation. Artificial P. tenuiflora seeds addition may
be required to accelerate old field succession toward matured grassland.
PMID- 25110721
TI - Biomarker Development for Brain-Based Disorders: Recent Progress in Psychiatry.
AB - Biomarkers are biological measures that are indicative of a specific disorder,
its severity or response to treatment. They are widely used in many areas of
medicine, but biomarker development for brain-based disorders lags behind. Using
examples from the field of psychiatry, this article reviews the concepts of
biomarkers, challenges to their development and the recent progress along those
lines. In addition to discussing historical biomarker candidates such as cortisol
or catecholamine levels, we include progress from recent genetic, epigenetic,
proteomic, neuroimaging and EEG studies. Successful identification of biomarkers
will advance the field of psychiatry towards the goal of biological tests for
diagnosis, symptom management and treatment response.
PMID- 25110724
TI - Gait signal analysis with similarity measure.
AB - Human gait decision was carried out with the help of similarity measure design.
Gait signal was selected through hardware implementation including all in one
sensor, control unit, and notebook with connector. Each gait signal was
considered as high dimensional data. Therefore, high dimensional data analysis
was considered via heuristic technique such as the similarity measure. Each human
pattern such as walking, sitting, standing, and stepping up was obtained through
experiment. By the results of the analysis, we also identified the overlapped and
nonoverlapped data relation, and similarity measure analysis was also
illustrated, and comparison with conventional similarity measure was also carried
out. Hence, nonoverlapped data similarity analysis provided the clue to solve the
similarity of high dimensional data. Considered high dimensional data analysis
was designed with consideration of neighborhood information. Proposed similarity
measure was applied to identify the behavior patterns of different persons, and
different behaviours of the same person. Obtained analysis can be extended to
organize health monitoring system for specially elderly persons.
PMID- 25110723
TI - Mitigative effect of erythromycin on PMMA challenged preosteoblastic MC3T3-E1
cells.
AB - BACKGROUND: Aseptic loosening (AL) is a major complication of total joint
replacement. Recent approaches to limiting AL have focused on inhibiting
periprosthetic inflammation and osteoclastogenesis. QUESTIONS/PURPOSES: The
purpose of this study was to determine the effects of erythromycin (EM) on
polymethylmethacrylate (PMMA) particle-challenged MC3T3 osteoblast precursor
cells. MetHODS: MC3T3 cells were pretreated with EM (0-10 MUg/mL) and then
stimulated with PMMA (1 mg/mL). Cell viability was evaluated by both a lactate
dehydrogenase (LDH) release assay and cell counts. Cell differentiation was
determined by activity of alkaline phosphatase (ALP). Gene expression was
measured via real-time quantitative RT-PCR. RESULTS: We found that exposure to
PMMA particles reduced cellular viability and osteogenetic potential in MC3T3
cell line. EM treatment mitigated the effects of PMMA particles on the
proliferation, viability and differentiation of MC3T3 cells. PMMA decreased the
gene expression of Runx2, osterix and osteocalcin, which can be partially
restored by EM treatment. Furthermore, EM suppressed PMMA- induced increase of NF
kappaB gene expression. CONCLUSIONS: These data demonstrate that EM mitigates the
effects of PMMA on MC3T3 cell viability and differentiation, in part through
downregulation of NF-kappaB pathway. EM appeared to represent an anabolic agent
on MC3T3 cells challenged with PMMA particles.
PMID- 25110725
TI - Detecting community structures in networks by label propagation with prediction
of percolation transition.
AB - Though label propagation algorithm (LPA) is one of the fastest algorithms for
community detection in complex networks, the problem of trivial solutions
frequently occurring in the algorithm affects its performance. We propose a label
propagation algorithm with prediction of percolation transition (LPAp). After
analyzing the reason for multiple solutions of LPA, by transforming the process
of community detection into network construction process, a trivial solution in
label propagation is considered as a giant component in the percolation
transition. We add a prediction process of percolation transition in label
propagation to delay the occurrence of trivial solutions, which makes small
communities easier to be found. We also give an incomplete update condition which
considers both neighbor purity and the contribution of small degree vertices to
community detection to reduce the computation time of LPAp. Numerical tests are
conducted. Experimental results on synthetic networks and real-world networks
show that the LPAp is more accurate, more sensitive to small community, and has
the ability to identify a single community structure. Moreover, LPAp with the
incomplete update process can use less computation time than LPA, nearly without
modularity loss.
PMID- 25110726
TI - Coal fly ash ceramics: preparation, characterization, and use in the hydrolysis
of sucrose.
AB - Coal ash is a byproduct of mineral coal combustion in thermal power plants. This
residue is responsible for many environmental problems because it pollutes soil,
water, and air. Thus, it is important to find ways to reuse it. In this study,
coal fly ash, obtained from the Presidente Medici Thermal Power Plant, was
utilized in the preparation of ceramic supports for the immobilization of the
enzyme invertase and subsequent hydrolysis of sucrose. Coal fly ash supports were
prepared at several compaction pressures (63.66-318.30 MPa) and sintered at 1200
degrees C for 4 h. Mineralogical composition (by X-ray diffraction) and surface
area were studied. The ceramic prepared with 318.30 MPa presented the highest
surface area (35 m(2)/g) and amount of immobilized enzyme per g of support (76.6
mg/g). In assays involving sucrose inversion, it showed a high degree of
hydrolysis (around 81%) even after nine reuses and 30 days' storage. Therefore,
coal fly ash ceramics were demonstrated to be a promising biotechnological
alternative as an immobilization support for the hydrolysis of sucrose.
PMID- 25110727
TI - Technology efficacy in active prosthetic knees for transfemoral amputees: a
quantitative evaluation.
AB - Several studies have presented technological ensembles of active knee systems for
transfemoral prosthesis. Other studies have examined the amputees' gait
performance while wearing a specific active prosthesis. This paper combined both
insights, that is, a technical examination of the components used, with an
evaluation of how these improved the gait of respective users. This study aims to
offer a quantitative understanding of the potential enhancement derived from
strategic integration of core elements in developing an effective device. The
study systematically discussed the current technology in active transfemoral
prosthesis with respect to its functional walking performance amongst above-knee
amputee users, to evaluate the system's efficacy in producing close-to-normal
user performance. The performances of its actuator, sensory system, and control
technique that are incorporated in each reported system were evaluated separately
and numerical comparisons were conducted based on the percentage of amputees'
gait deviation from normal gait profile points. The results identified particular
components that contributed closest to normal gait parameters. However, the
conclusion is limitedly extendable due to the small number of studies. Thus, more
clinical validation of the active prosthetic knee technology is needed to better
understand the extent of contribution of each component to the most functional
development.
PMID- 25110728
TI - Scene consistency verification based on PatchNet.
AB - In the real world, the object does not exist in isolation, and it always appears
in a certain scene. Usually the object is fixed in a particular scene and even in
special spatial location. In this paper, we propose a method for judging scene
consistency effectively. Scene semantics and geometry relation play a key role.
In this paper, we use PatchNet to deal with these high-level scene structures. We
construct a consistent scene database, using semantic information of PatchNet to
determine whether the scene is consistent. The effectiveness of the proposed
algorithm is verified by a lot of experiments.
PMID- 25110729
TI - Inference for one-way ANOVA with equicorrelation error structure.
AB - We consider inferences in a one-way ANOVA model with equicorrelation error
structures. Hypotheses of the equality of the means are discussed. A generalized
F-test has been proposed by in the literature to compare the means of all
populations. However, they did not discuss the performance of that test. We
propose two methods, a generalized pivotal quantities-based method and a
parametric bootstrap method, to test the hypotheses of equality of the means. We
compare the empirical performance of the proposed tests with the generalized F
test. It can be seen from the simulation results that the generalized F-test does
not perform well in terms of Type I error rate, and the proposed tests perform
much better. We also provide corresponding simultaneous confidence intervals for
all pair-wise differences of the means, whose coverage probabilities are close to
the confidence level.
PMID- 25110730
TI - Enoxaparin prevents steroid-related avascular necrosis of the femoral head.
AB - Nontraumatic osteonecrosis of the femoral head is still a challenging problem in
orthopedic surgery. It is responsible for 10% of the 500,000 hip replacement
surgeries in the USA and affects relatively young, active patients in particular.
Main reasons for nontraumatic osteonecrosis are glucocorticoid use, alcoholism,
thrombophilia, and hypofibrinolysis (Glueck et al., 1997; Orth and Anagnostakos,
2013). One pathomechanism of steroid-induced osteonecrosis is thought to be
impaired blood flow to the femoral head caused by increased thrombus formation
and vasoconstriction. To investigate the preventive effect of enoxaparin on
steroid-related osteonecrosis, we used male New Zealand white rabbits.
Osteonecrosis was induced by methylprednisolone-injection (1 * 20 mg/kg body
weight). Control animals were treated with phosphate-buffered saline. Treatment
consisted of an injection of 11.7 mg/kg body weight of enoxaparin per day
(Clexane) in addition to methylprednisolone. Four weeks after methylprednisolone
injection the animals were sacrificed. Histology (hematoxylin-eosin and Ladewig
staining) was performed, and empty lacunae and histological signs of
osteonecrosis were quantified. Histomorphometry revealed a significant increase
in empty lacunae and necrotic changed osteocytes in glucocorticoid-treated
animals as compared with the glucocorticoid- and Clexane-treated animals and with
the control group. No significant difference was detected between the
glucocorticoid and Clexane group and the control group. This finding suggests
that cotreatment with enoxaparin has the potential to prevent steroid-associated
osteonecrosis.
PMID- 25110732
TI - Value and vulnerability assessment of a historic tomb for conservation.
AB - Monumental tombs reflect various social, cultural, architectural, religious,
economic, and engineering features of a community. However, environmental
weathering, natural disasters, poor maintenance, vandalism, and misuse
unfortunately pose serious threats to these cultural assets. Historic monuments
are often exposed to the highest risk due to their vulnerability. The Ottoman
style Nisanci Hamza Pasa tomb located in Karacaahmet Cemetery, Istanbul, the
largest and oldest public cemetery in Turkey, is a case in point. The tomb
consisting of six granite columns and a brick dome supported by six arches was
constructed in 1605. Cracks, material loss, and decay as a result of adverse
environmental effects and past earthquakes are evident. Therefore, this paper
analyses the overall value of the tomb with respect to its historical, communal,
evidential, and aesthetic aspects. Using the finite element approach and data on
the tomb's material properties, a structural analysis under the self-weight and a
time history analysis based on the earthquake ground motion data recorded in
Duzce, Turkey, in November 1999 were conducted to encourage the conservation of
this tomb and similar cultural heritage assets all over the world. The damage
observed in the structure is congruent with the analysis results.
PMID- 25110731
TI - Laser welded versus resistance spot welded bone implants: analysis of the thermal
increase and strength.
AB - INTRODUCTION: The first aim of this "ex vivo split mouth" study was to compare
the thermal elevation during the welding process of titanium bars to titanium
implants inserted in pig jaws by a thermal camera and two thermocouples. The
second aim was to compare the strength of the joints by a traction test with a
dynamometer. MATERIALS AND METHODS: Six pigs' jaws were used and three implants
were placed on each side of them for a total of 36 fixtures. Twelve bars were
connected to the abutments (each bar on three implants) by using, on one side,
laser welding and, on the other, resistance spot welding. Temperature variations
were recorded by thermocouples and by thermal camera while the strength of the
welded joint was analyzed by a traction test. RESULTS: For increasing
temperature, means were 36.83 and 37.06, standard deviations 1.234 and 1.187, and
P value 0.5763 (not significant). For traction test, means were 195.5 and 159.4,
standard deviations 2.00 and 2.254, and P value 0.0001 (very significant).
CONCLUSION: Laser welding was demonstrated to be able to connect titanium implant
abutments without the risk of thermal increase into the bone and with good
results in terms of mechanical strength.
PMID- 25110733
TI - Arsenic modulates posttranslational S-nitrosylation and translational proteome in
keratinocytes.
AB - Arsenic is a class I human carcinogen (such as inducing skin cancer) by its
prominent chemical interaction with protein thio (-SH) group. Therefore, arsenic
may compromise protein S-nitrosylation by competing the -SH binding activity. In
the present study, we aimed to understand the influence of arsenic on protein S
nitrosylation and the following proteomic changes. By using primary human skin
keratinocyte, we found that arsenic treatment decreased the level of protein S
nitrosylation. This was coincident to the decent expressions of endothelial
nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS). By using
LC-MS/MS, around twenty S-nitrosoproteins were detected in the biotin-switched
eluent. With the interest that arsenic not only regulates posttranslational S
nitrosylation but also separately affects protein's translation expression, we
performed two-dimensional gel electrophoresis and found that 8 proteins were
significantly decreased during arsenic treatment. Whether these decreased
proteins are the consequence of protein S-nitrosylation will be further
investigated. Taken together, these results provide a finding that arsenic can
deplete the binding activity of NO and therefore reduce protein S-nitrosylation.
PMID- 25110735
TI - Mathematical analysis of the effect of rotor geometry on cup anemometer response.
AB - The calibration coefficients of two commercial anemometers equipped with
different rotors were studied. The rotor cups had the same conical shape, while
the size and distance to the rotation axis varied. The analysis was based on the
2-cup positions analytical model, derived using perturbation methods to include
second-order effects such as pressure distribution along the rotating cups and
friction. The comparison with the experimental data indicates a nonuniform
distribution of aerodynamic forces on the rotating cups, with higher forces
closer to the rotating axis. The 2-cup analytical model is proven to be accurate
enough to study the effect of complex forces on cup anemometer performance.
PMID- 25110734
TI - PEEK cages versus PMMA spacers in anterior cervical discectomy: comparison of
fusion, subsidence, sagittal alignment, and clinical outcome with a minimum 1
year follow-up.
AB - PURPOSE: To compare radiographic and clinical outcomes after anterior cervical
discectomy in patients with cervical degenerative disc disease using PEEK cages
or PMMA spacers with a minimum 1-year follow-up. METHODS: Anterior cervical
discectomy was performed in 107 patients in one or two levels using empty PEEK
cages (51 levels), Sulcem PMMA spacers (49 levels) or Palacos PMMA spacers (41
levels) between January, 2005 and February, 2009. Bony fusion, subsidence, and
sagittal alignment were retrospectively assessed in CT scans and radiographs at
follow-up. Clinical outcome was measured using the VAS, NDI, and SF-36. RESULTS:
Bony fusion was assessed in 65% (PEEK cage), 57% (Sulcem), and 46% (Palacos)
after a mean follow-up of 2.5 years. Mean subsidence was 2.3-2.6 mm without
significant differences between the groups. The most pronounced loss of lordosis
was found in PEEK cages (-4.1 degrees ). VAS was 3.1 (PEEK cage), 3.6 (Sulcem),
and 2.7 (Palacos) without significant differences. Functional outcome in the PEEK
cage and Palacos group was superior to the Sulcem group. CONCLUSIONS: The
substitute groups showed differing fusion rates. Clinical outcome, however,
appears to be generally not correlated with fusion status or subsidence. We could
not specify a superior disc substitute for anterior cervical discectomy. This
trial is registered with DRKS00003591.
PMID- 25110736
TI - A hop count based heuristic routing protocol for mobile delay tolerant networks.
AB - Routing in delay tolerant networks (DTNs) is a challenge since it must handle
network partitioning, long delays, and dynamic topology. Meanwhile, routing
protocols of the traditional mobile ad hoc networks (MANETs) cannot work well due
to the failure of its assumption that most network connections are available. In
this paper, we propose a hop count based heuristic routing protocol by utilizing
the information carried by the peripatetic packets in the network. A heuristic
function is defined to help in making the routing decision. We formally define a
custom operation for square matrices so as to transform the heuristic value
calculation into matrix manipulation. Finally, the performance of our proposed
algorithm is evaluated by the simulation results, which show the advantage of
such self-adaptive routing protocol in the diverse circumstance of DTNs.
PMID- 25110737
TI - Constructing topic models of Internet of Things for information processing.
AB - Internet of Things (IoT) is regarded as a remarkable development of the modern
information technology. There is abundant digital products data on the IoT,
linking with multiple types of objects/entities. Those associated entities carry
rich information and usually in the form of query records. Therefore,
constructing high quality topic hierarchies that can capture the term
distribution of each product record enables us to better understand users' search
intent and benefits tasks such as taxonomy construction, recommendation systems,
and other communications solutions for the future IoT. In this paper, we propose
a novel record entity topic model (RETM) for IoT environment that is associated
with a set of entities and records and a Gibbs sampling-based algorithm is
proposed to learn the model. We conduct extensive experiments on real-world
datasets and compare our approach with existing methods to demonstrate the
advantage of our approach.
PMID- 25110738
TI - A spread willingness computing-based information dissemination model.
AB - This paper constructs a kind of spread willingness computing based on information
dissemination model for social network. The model takes into account the impact
of node degree and dissemination mechanism, combined with the complex network
theory and dynamics of infectious diseases, and further establishes the dynamical
evolution equations. Equations characterize the evolutionary relationship between
different types of nodes with time. The spread willingness computing contains
three factors which have impact on user's spread behavior: strength of the
relationship between the nodes, views identity, and frequency of contact.
Simulation results show that different degrees of nodes show the same trend in
the network, and even if the degree of node is very small, there is likelihood of
a large area of information dissemination. The weaker the relationship between
nodes, the higher probability of views selection and the higher the frequency of
contact with information so that information spreads rapidly and leads to a wide
range of dissemination. As the dissemination probability and immune probability
change, the speed of information dissemination is also changing accordingly. The
studies meet social networking features and can help to master the behavior of
users and understand and analyze characteristics of information dissemination in
social network.
PMID- 25110739
TI - A review of norms and normative multiagent systems.
AB - Norms and normative multiagent systems have become the subjects of interest for
many researchers. Such interest is caused by the need for agents to exploit the
norms in enhancing their performance in a community. The term norm is used to
characterize the behaviours of community members. The concept of normative
multiagent systems is used to facilitate collaboration and coordination among
social groups of agents. Many researches have been conducted on norms that
investigate the fundamental concepts, definitions, classification, and types of
norms and normative multiagent systems including normative architectures and
normative processes. However, very few researches have been found to
comprehensively study and analyze the literature in advancing the current state
of norms and normative multiagent systems. Consequently, this paper attempts to
present the current state of research on norms and normative multiagent systems
and propose a norm's life cycle model based on the review of the literature.
Subsequently, this paper highlights the significant areas for future work.
PMID- 25110740
TI - Matrix transformations between certain sequence spaces over the non-Newtonian
complex field.
AB - In some cases, the most general linear operator between two sequence spaces is
given by an infinite matrix. So the theory of matrix transformations has always
been of great interest in the study of sequence spaces. In the present paper, we
introduce the matrix transformations in sequence spaces over the field C(*) and
characterize some classes of infinite matrices with respect to the non-Newtonian
calculus. Also we give the necessary and sufficient conditions on an infinite
matrix transforming one of the classical sets over C(*) to another one.
Furthermore, the concept for sequence-to-sequence and series-to-series methods of
summability is given with some illustrated examples.
PMID- 25110741
TI - Multispectral image compression based on DSC combined with CCSDS-IDC.
AB - Remote sensing multispectral image compression encoder requires low complexity,
high robust, and high performance because it usually works on the satellite where
the resources, such as power, memory, and processing capacity, are limited. For
multispectral images, the compression algorithms based on 3D transform (like 3D
DWT, 3D DCT) are too complex to be implemented in space mission. In this paper,
we proposed a compression algorithm based on distributed source coding (DSC)
combined with image data compression (IDC) approach recommended by CCSDS for
multispectral images, which has low complexity, high robust, and high
performance. First, each band is sparsely represented by DWT to obtain wavelet
coefficients. Then, the wavelet coefficients are encoded by bit plane encoder
(BPE). Finally, the BPE is merged to the DSC strategy of Slepian-Wolf (SW) based
on QC-LDPC by deep coupling way to remove the residual redundancy between the
adjacent bands. A series of multispectral images is used to test our algorithm.
Experimental results show that the proposed DSC combined with the CCSDS-IDC (DSC
CCSDS)-based algorithm has better compression performance than the traditional
compression approaches.
PMID- 25110742
TI - Recent advances in information technology.
PMID- 25110743
TI - A rhythm-based authentication scheme for smart media devices.
AB - In recent years, ubiquitous computing has been rapidly emerged in our lives and
extensive studies have been conducted in a variety of areas related to smart
devices, such as tablets, smartphones, smart TVs, smart refrigerators, and smart
media devices, as a measure for realizing the ubiquitous computing. In
particular, smartphones have significantly evolved from the traditional feature
phones. Increasingly higher-end smartphone models that can perform a range of
functions are now available. Smart devices have become widely popular since they
provide high efficiency and great convenience for not only private daily
activities but also business endeavors. Rapid advancements have been achieved in
smart device technologies to improve the end users' convenience. Consequently,
many people increasingly rely on smart devices to store their valuable and
important data. With this increasing dependence, an important aspect that must be
addressed is security issues. Leaking of private information or sensitive
business data due to loss or theft of smart devices could result in exorbitant
damage. To mitigate these security threats, basic embedded locking features are
provided in smart devices. However, these locking features are vulnerable. In
this paper, an original security-locking scheme using a rhythm-based locking
system (RLS) is proposed to overcome the existing security problems of smart
devices. RLS is a user-authenticated system that addresses vulnerability issues
in the existing locking features and provides secure confidentiality in addition
to convenience.
PMID- 25110744
TI - Predicting the use of public transportation: a case study from Putrajaya,
Malaysia.
AB - Putrajaya is a new federal administrative capital of Malaysia which has been set
to achieve a 70% share of all travels by public transport in the city area.
However, the current modal split between the public transport and private
transport is 15:85. In order to understand travelers' willingness to use the
public transport, a conceptual model has been developed to determine the factors
that affect them to use the public transport instead of travelling in their own
cars. Various variables such as service quality, environmental impact, attitude,
and behavior intention were analyzed and tested using structural equation model
(SEM). Results indicate that the service quality and attitude are found to have
positive effects on the behavioral intention of taking the public transport.
Other than this, this study also shows that the service quality and environmental
impact have some positive influences on the attitude to using the public
transport. However, environmental impact has no significant, positive, and direct
effect on behavioral intention. The results of this study demonstrate that the
model that was developed is useful in predicting the public transport and it
could provide a more complete understanding of behavioral intention towards
public transport use.
PMID- 25110745
TI - Hybrid polylingual object model: an efficient and seamless integration of Java
and native components on the Dalvik virtual machine.
AB - JNI in the Android platform is often observed with low efficiency and high coding
complexity. Although many researchers have investigated the JNI mechanism, few of
them solve the efficiency and the complexity problems of JNI in the Android
platform simultaneously. In this paper, a hybrid polylingual object (HPO) model
is proposed to allow a CAR object being accessed as a Java object and as vice in
the Dalvik virtual machine. It is an acceptable substitute for JNI to reuse the
CAR-compliant components in Android applications in a seamless and efficient way.
The metadata injection mechanism is designed to support the automatic mapping and
reflection between CAR objects and Java objects. A prototype virtual machine,
called HPO-Dalvik, is implemented by extending the Dalvik virtual machine to
support the HPO model. Lifespan management, garbage collection, and data type
transformation of HPO objects are also handled in the HPO-Dalvik virtual machine
automatically. The experimental result shows that the HPO model outweighs the
standard JNI in lower overhead on native side, better executing performance with
no JNI bridging code being demanded.
PMID- 25110746
TI - Utility-oriented placement of actuator nodes with a collaborative serving scheme
for facilitated business and working environments.
AB - Places to be served by cyber-physical systems (CPS) are usually distributed
unevenly over the area. Thus, different areas usually have different importance
and values of serving. In other words, serving power can be excessive or
insufficient in practice. Therefore, actuator nodes (ANs) in CPS should be
focused on serving around points of interest (POIs) with considerations of
"service utility." In this paper, a utility-oriented AN placement framework with
a collaborative serving scheme is proposed. Through spreading serving duties
among correctly located ANs, deployment cost can be reduced, utility of ANs can
be fully utilized, and the system longevity can be improved. The problem has been
converted into a binary integer linear programming optimization problem. Service
fading, 3D placements, multiscenario placements, and fault-tolerant placements
have been modeled in the framework. An imitated example of a CPS deployment in a
smart laboratory has been used for evaluations.
PMID- 25110747
TI - Synchronization control for stochastic neural networks with mixed time-varying
delays.
AB - Synchronization control of stochastic neural networks with time-varying discrete
and continuous delays has been investigated. A novel control scheme is proposed
using the Lyapunov functional method and linear matrix inequality (LMI) approach.
Sufficient conditions have been derived to ensure the global asymptotical mean
square stability for the error system, and thus the drive system synchronizes
with the response system. Also, the control gain matrix can be obtained. With
these effective methods, synchronization can be achieved. Simulation results are
presented to show the effectiveness of the theoretical results.
PMID- 25110748
TI - QoS measurement of workflow-based web service compositions using Colored Petri
net.
AB - Workflow-based web service compositions (WB-WSCs) is one of the main composition
categories in service oriented architecture (SOA). Eflow, polymorphic process
model (PPM), and business process execution language (BPEL) are the main
techniques of the category of WB-WSCs. Due to maturity of web services, measuring
the quality of composite web services being developed by different techniques
becomes one of the most important challenges in today's web environments.
Business should try to provide good quality regarding the customers' requirements
to a composed web service. Thus, quality of service (QoS) which refers to
nonfunctional parameters is important to be measured since the quality degree of
a certain web service composition could be achieved. This paper tried to find a
deterministic analytical method for dependability and performance measurement
using Colored Petri net (CPN) with explicit routing constructs and application of
theory of probability. A computer tool called WSET was also developed for
modeling and supporting QoS measurement through simulation.
PMID- 25110750
TI - Design and implementation of hybrid CORDIC algorithm based on phase rotation
estimation for NCO.
AB - The numerical controlled oscillator has wide application in radar, digital
receiver, and software radio system. Firstly, this paper introduces the
traditional CORDIC algorithm. Then in order to improve computing speed and save
resources, this paper proposes a kind of hybrid CORDIC algorithm based on phase
rotation estimation applied in numerical controlled oscillator (NCO). Through
estimating the direction of part phase rotation, the algorithm reduces part phase
rotation and add-subtract unit, so that it decreases delay. Furthermore, the
paper simulates and implements the numerical controlled oscillator by Quartus II
software and Modelsim software. Finally, simulation results indicate that the
improvement over traditional CORDIC algorithm is achieved in terms of ease of
computation, resource utilization, and computing speed/delay while maintaining
the precision. It is suitable for high speed and precision digital modulation and
demodulation.
PMID- 25110749
TI - acACS: improving the prediction accuracy of protein subcellular locations and
protein classification by incorporating the average chemical shifts composition.
AB - The chemical shift is sensitive to changes in the local environments and can
report the structural changes. The structure information of a protein can be
represented by the average chemical shifts (ACS) composition, which has been
broadly applied for enhancing the prediction accuracy in protein subcellular
locations and protein classification. However, different kinds of ACS composition
can solve different problems. We established an online web server named acACS,
which can convert secondary structure into average chemical shift and then
compose the vector for representing a protein by using the algorithm of auto
covariance. Our solution is easy to use and can meet the needs of users.
PMID- 25110751
TI - Assessment of potential location of high arsenic contamination using fuzzy
overlay and spatial anisotropy approach in iron mine surrounding area.
AB - Fuzzy overlay approach on three raster maps including land slope, soil type, and
distance to stream can be used to identify the most potential locations of high
arsenic contamination in soils. Verification of high arsenic contamination was
made by collection samples and analysis of arsenic content and interpolation
surface by spatial anisotropic method. A total of 51 soil samples were collected
at the potential contaminated location clarified by fuzzy overlay approach. At
each location, soil samples were taken at the depth of 0.00-1.00 m from the
surface ground level. Interpolation surface of the analysed arsenic content using
spatial anisotropic would verify the potential arsenic contamination location
obtained from fuzzy overlay outputs. Both outputs of the spatial surface
anisotropic and the fuzzy overlay mapping were significantly spatially conformed.
Three contaminated areas with arsenic concentrations of 7.19 +/- 2.86, 6.60 +/-
3.04, and 4.90 +/- 2.67 mg/kg exceeded the arsenic content of 3.9 mg/kg, the
maximum concentration level (MCL) for agricultural soils as designated by Office
of National Environment Board of Thailand. It is concluded that fuzzy overlay
mapping could be employed for identification of potential contamination area with
the verification by surface anisotropic approach including intensive sampling and
analysis of the substances of interest.
PMID- 25110752
TI - Prediction of maize single cross hybrids using the total effects of associated
markers approach assessed by cross-validation and regional trials.
AB - The present study aimed to predict the performance of maize hybrids and assess
whether the total effects of associated markers (TEAM) method can correctly
predict hybrids using cross-validation and regional trials. The training was
performed in 7 locations of Southern Brazil during the 2010/11 harvest. The
regional assays were conducted in 6 different South Brazilian locations during
the 2011/12 harvest. In the training trial, 51 lines from different backgrounds
were used to create 58 single cross hybrids. Seventy-nine microsatellite markers
were used to genotype these 51 lines. In the cross-validation method the
predictive accuracy ranged from 0.10 to 0.96, depending on the sample size.
Furthermore, the accuracy was 0.30 when the values of hybrids that were not used
in the training population (119) were predicted for the regional assays.
Regarding selective loss, the TEAM method correctly predicted 50% of the hybrids
selected in the regional assays. There was also loss in only 33% of cases; that
is, only 33% of the materials predicted to be good in training trial were
considered to be bad in regional assays. Our results show that the predictive
validation of different crop conditions is possible, and the cross-validation
results strikingly represented the field performance.
PMID- 25110753
TI - A fast density-based clustering algorithm for real-time Internet of Things
stream.
AB - Data streams are continuously generated over time from Internet of Things (IoT)
devices. The faster all of this data is analyzed, its hidden trends and patterns
discovered, and new strategies created, the faster action can be taken, creating
greater value for organizations. Density-based method is a prominent class in
clustering data streams. It has the ability to detect arbitrary shape clusters,
to handle outlier, and it does not need the number of clusters in advance.
Therefore, density-based clustering algorithm is a proper choice for clustering
IoT streams. Recently, several density-based algorithms have been proposed for
clustering data streams. However, density-based clustering in limited time is
still a challenging issue. In this paper, we propose a density-based clustering
algorithm for IoT streams. The method has fast processing time to be applicable
in real-time application of IoT devices. Experimental results show that the
proposed approach obtains high quality results with low computation time on real
and synthetic datasets.
PMID- 25110755
TI - Multilayer perceptron for robust nonlinear interval regression analysis using
genetic algorithms.
AB - On the basis of fuzzy regression, computational models in intelligence such as
neural networks have the capability to be applied to nonlinear interval
regression analysis for dealing with uncertain and imprecise data. When training
data are not contaminated by outliers, computational models perform well by
including almost all given training data in the data interval. Nevertheless,
since training data are often corrupted by outliers, robust learning algorithms
employed to resist outliers for interval regression analysis have been an
interesting area of research. Several approaches involving computational
intelligence are effective for resisting outliers, but the required parameters
for these approaches are related to whether the collected data contain outliers
or not. Since it seems difficult to prespecify the degree of contamination
beforehand, this paper uses multilayer perceptron to construct the robust
nonlinear interval regression model using the genetic algorithm. Outliers beyond
or beneath the data interval will impose slight effect on the determination of
data interval. Simulation results demonstrate that the proposed method performs
well for contaminated datasets.
PMID- 25110754
TI - High association between human circulating microRNA-497 and acute myocardial
infarction.
AB - Recent papers have reported the fundamental roles of miR-497 in infarction which
acute myocardial infarction (AMI) belongs to. However, the expression levels of
miR-497 in AMI patients were unclear, especially the circulating miR-497 that was
detectable in the human plasma. In this study, we focused on the expression
levels of circulating miR-497 in AMI and the roles of plasma miR-497 as a
promising biomarker for AMI. The plasma miR-497 levels were detected from 27 AMI
patients and 31 healthy volunteers by qRT-PCR. The cTnI concentrations of these
samples were also analyzed by ELISA. Results showed circulating miR-497 levels
were upregulated in AMI patients at 4 h, 8 h, 12 h, and 24 h, by contrast to
those in control. Interestingly, time courses of circulating miR-497 levels
displayed similar trends to that of cTnI concentrations in AMI patients; further
study revealed the high correlation between circulating miR-497 and cTnI
concentrations (r = 0.573, P < 0.001). At last, the receiver operating
characteristic (ROC) curve was performed and declared that there was a
faithworthy sensitivity and specificity to identify the AMI patients by using
circulating miR-497. In conclusion, circulating miR-497 might be a promising
biomarker for AMI identification and there was high association between human miR
497 and acute myocardial infarction.
PMID- 25110756
TI - Process design of a ball joint, considering caulking and pull-out strength.
AB - A ball joint for an automobile steering system is a pivot component which is
connected to knuckle and lower control arm. The manufacturing process for its
caulking comprises spinning and deforming. In this study, the process was
simulated by flexible multibody dynamics. The caulking was evaluated
qualitatively through numerical analysis and inspecting a plastically deformed
shape. The structural responses of a ball joint, namely, pull-out strength and
stiffness, are commonly investigated in the development process. Thus, following
the caulking analysis, the structural responses were considered. In addition,
three design variables related to the manufacturing process were defined, and the
effects of design variables with respect to pull-out strength, caulking depth,
and maximum stress were obtained by introducing the DOE using an L9 orthogonal
array. Finally, the optimum design maximizing the pull-out strength was
suggested. For the final design, the caulking quality and the pull-out strength
were investigated by making six samples and their tests.
PMID- 25110758
TI - A new step, a new challenge, a new beginning.
PMID- 25110757
TI - Developing Attention: Behavioral and Brain Mechanisms.
AB - Brain networks underlying attention are present even during infancy and are
critical for the developing ability of children to control their emotions and
thoughts. For adults, individual differences in the efficiency of attentional
networks have been related to neuromodulators and to genetic variations. We have
examined the development of attentional networks and child temperament in a
longitudinal study from infancy (7 months) to middle childhood (7 years). Early
temperamental differences among infants, including smiling and laughter and vocal
reactivity, are related to self-regulation abilities at 7 years. However, genetic
variations related to adult executive attention, while present in childhood, are
poor predictors of later control, in part because individual genetic variationmay
have many small effects and in part because their influence occurs in interaction
with caregiver behavior and other environmental influences. While brain areas
involved in attention are present during infancy, their connectivity changes and
leads to improvement in control of behavior. It is also possible to influence
control mechanisms through training later in life. The relation between
maturation and learning may allow advances in our understanding of human brain
development.
PMID- 25110759
TI - Ultrasound evaluation of mediastinal lymphadenopathy in patients with
sarcoidosis.
AB - AIM: Mediastinal lymphadenopathy is a typical feature of pulmonary sarcoidosis
and an important parameter for diagnosis and follow-up. The present feasibility
study is the first to elucidate the role of transthoracic mediastinal
ultrasonography (US) for evaluation and staging of lymphadenopathy in patients
with sarcoidosis. MATERIAL AND METHOD: Fifty patients with sarcoidosis were
subjected to high-definition mediastinal US. The sonographic lymph node status
was compared with the radiologic staging - the prevailing gold standard. RESULTS:
Mediastinal regions and landmarks could reliably be assessed by ultrasound in
45/50 (90%) of sarcoidosis patients. Lymphadenopathy was sonographically
documented in 29/50 (58%) of the patients (sensitivity 89%, specificity 76%, PPV
86%, NPV 81%, accuracy 84%). There was a marked concordance between US
confirmation of lymphadenopathy and radiologic staging (k=0.67, p<0.001).
CONCLUSIONS: Transthoracic US qualifies for the demonstration of the mediastinal
regions and lymphadenopathy in patients with sarcoidosis. The procedure is
facilitated by frequent and distinct mediastinal lymph node enlargement due to
sarcoidosis. Prospective studies are required to find out whether mediastinal US
adds value to conventional radiologic staging and provides a clinically
advantage, particularly in the follow-up of patients with sarcoidosis.
PMID- 25110760
TI - The effectiveness of power Doppler vocal fremitus imaging in the diagnosis of
breast hamartoma.
AB - OBJECTIVES: To evaluate the usefulness of power Doppler vocal fremitus (PDVF)
breast sonography for differentiation of hamartomas from other breast (malign or
benign) masses. MATERIAL AND METHODS: Two hundred and six breast masses in 180
women were evaluated. The breast lesions were scanned first by mammography (MG),
then by ultrasonography (US) with PDVF imaging. Finally, biopsy was performed on
lesions suspicious for malignancy (n=172). We used PDVF imaging to evaluate
whether the Power acoustic Doppler artifact existed in all breast lesions.
RESULTS: Pathology results of 172 biopsied lesions showed that 83 were malign and
89 masses were benign. Totally 39 breast hamartomas were diagnosed radiologically
(n=25) or histopathologically (n=14). All hamartomas (n=39) produced the power
acoustic Doppler artifact as the surrounding tissue at the same depth in PDVF
imaging. On the other hand, none of the malign or benign lesions, apart from
hamartomas, evidenced a similar vibrational artifact as the surrounding tissue at
the same depth in the PDVF imaging. CONCLUSION: PDVF imaging during breast
sonography is an invaluable technique in the identification of breast hamartomas
from other benign or malign breast masses.
PMID- 25110761
TI - The measurement of the prostatic resistive index is a reliable ultrasonographic
tool to stratify symptoms of patients with benign prosthatic hyperplasia.
AB - AIMS: To evaluate the correlation between lower urinary tract symptoms (LUTS) and
the resistive index (RI) of the transitional (TZ) and peripheral zone (PZ) of the
prostate and to assess the impact of alpha blocker (AB) treatment on RI changes.
MATERIAL AND METHODS: TZ-RI and PZ-RI values of 60 patients with LUTS were
calculated by using transrectal ultrasound (TRUS). Correlations between the
severity of LUTS and RI values were established. Then, AB was given to moderately
and severe symptomatic patients with LUTS. One month after AB usage, TRUS was
applied to assess the impact of AB on the TZ-RI, PZ-RI and the international
prostate symptom score (IPSS). RESULTS: Participants were divided into 3 groups
as mild (n=14), moderate (n=25) and severe symptomatic (n=21) patients. Mean TZ
RI and PZ-RI were statistically different between the three groups (p<0.01). TZ
RI and PZ-RI were correlated with the severity of LUTS (r=0.757, p<0.01 and
r=0.699, p<0.01 respectively). A decrease in symptom severity and RI values in
moderate and severe symptomatic groups were significant after AB treatment.
CONCLUSIONS: TZ-RI and PZ-RI values can reflect the severity of LUTS and the AB
treatment decreases the TZ-RI and the PZ-RI. Measuring the RI of the prostate by
TRUS can be a useful tool to stratify LUTS's severity.
PMID- 25110762
TI - Musculoskeletal ultrasound guided manoeuvres - a security profile.
AB - BACKGROUND: In daily rheumatology clinical practice, routine interventional
musculoskeletal ultrasound (MSUS) guided maneuvers such as aspiration,
intraarticular or periarticular drug injections require efficient cleaning and
disinfection methods for both transducer and patient's skin. AIM: To study the
efficacy of probe and skin disinfection measures after using simple protocols, to
identify the prevalence of septic and other drug related side effects after MSUS
guided interventions and to quantify the total procedure time. MATERIAL AND
METHODS: Recruitment of consecutive patients with different joint/ periarticular
MSUS guided interventions was made in 3 medical centers. Bacterial load was
determined on the transducers footprint after dry cleaning with the removal of
any gel trace and on patients' skin after rigorous skin disinfection with either
Bethadine or alcohol 70 degrees and Bethadine. Non-sterile gel was used as an
ultrasound transmission medium. The time spent for some of the invasive
procedures was quantified. RESULTS: Nine hundred and ninety eight MSUS guided
interventional maneuvers were performed in 945 patients with inflammatory and
degenerative musculoskeletal pathologies. Staphylococcus epidermidis was
identified in 13.33% cases of the skin bacterial load analysis and in 37.50%
cases of the footprint analysis. In two patients pathogenetic germs were detected
on the skin. No septic post-procedural complications were reported. In 0.6% of
the cohort other side effects occurred: aseptic osteonecrosis, skin
depigmentation at injection site and iatrogenic microcristaline reactions. The
median time frame dedicated to the intervention was 6 minutes. CONCLUSION:
Rigorous transducer dry cleaning and Bethadine / Bethadine and alcohol 70 degrees
skin disinfection are efficacious methods. The risk for septic complications and
other drug related side effects related to MSUS guided injections is very low in
this context. A correct injection technique must accompany the previous requests.
Rapid and safe interventional maneuvers reduce the risks and control the costs of
the healthcare system.
PMID- 25110763
TI - Percutaneous treatment of symptomatic non-parasitic hepatic cysts. Initial
experience with single-session sclerotherapy with polidocanol.
AB - AIMS: Hepatic cysts have a prevalence of 2.5-7% and most of them are
asymptomatic. However, large cysts may cause complaints; in such cases an
appropriate treatment is necessary (open surgery, laparoscopic deroofing, removal
of cystic fluid and injection of a sclerosing agent. The aim of this study was to
assess the efficacy and safety of a single session technique with polidocanol in
the therapy of symptomatic non parasitic hepatic cysts. MATERIAL AND METHODS. The
study included 13 patients with symptomatic liver cysts (range 4-10 cm). All
patients underwent percutaneous aspiration of the liver cyst under ultrasound
guidance followed by instillation of polidocanol (3%, 4-10 ml). The patients were
followed up at 1, 3 and 12 months. The disappearance of the cyst or reduction in
volume more than 90% was considered successful. If the fluid was accumulated at
1month the procedure was repeated. If after the second injection the fluid
accumulation was more than 50% of the initial volume the case was considered a
failure and a laparoscopic deroofing was performed. RESULTS: The procedure was
successful in 10 patients, 9 after the first instillation and one after the
second (76.9%). The mean initial volume of cysts was 228 ml, and the mean
reduction in volume at 1, 3 and 12 months was 80.2%, 91.9% and 96.7%. The cyst
resolution was gradual with clinically significant cyst reduction achievement
within 1 year after therapy. In 3 patients the fluid reaccumulated at the same
volume despite 2 instillations. Those 3 cases the procedure was considered
failure and the patients were sent to surgery. In 2 patients (one successfully
treated and one with treatment failure) bleeding during the first puncture and
aspiration appeared and the therapy was postponed for 1 month. There were no
significant adverse effects, and all the patients had relief of symptoms after
therapy. CONCLUSIONS: This initial experience with percutaneous aspiration and
polidocanol sclerosis of hepatic cysts demonstrated that the technique is
efficient and safe.
PMID- 25110764
TI - Real time sonoelastographic evaluation of renal allografts in correlation with
clinical prognostic parameters: comparison of linear and convex transducers
according to segmental anatomy.
AB - BACKGROUND: Renal transplantation is the treatment of choice in end-stage renal
disease. Chronic allograft dysfunction is the leading cause of chronic allograft
failure. Surveillance biopsy is the only reliable tool to detect early fibrosis
in the allograft. There is a need for non-invasive methods for the detection of
early development of renal allograft fibrosis. AIMS: To analyze the reliability
of sonographic elasticity index and resistive index measurements in the
evaluation of renal transplant fibrosis using linear and convex transducers
according to segmental anatomy. MATERIALS AND METHODS: Elasticity index and
resistive index were measured in 28 renal transplants and correlated with
clinical prognostic parameters. Donor age above 50 years old, post
transplantation time over 60 months and serum creatinine level above 1.5 mg/dl
were defined as poor prognostic parameters. RESULTS: Renal transplant recipients
with serum creatinine level above 1.5 mg/dl demonstrated higher mean elasticity
index (p=0.006) with a convex probe and higher elasticity index in the middle
segments both with a convex and a matrix linear probe (p=0.026, p=0.001). Renal
transplant recipients with post-transplantation time of 60 months and more
demonstrated higher resistive index values in the middle segments (p=0.016).
CONCLUSIONS: Convex probe was able to detect the changes in mean stiffness better
than the matrix linear probe. The measurements from subsegments might suggest
that diffuse changes in stiffness can truly be detected in the middle segments or
that fibrotic processes start from the middle segments of the renal transplants.
Further studies correlated with histopathology are required to validate the
findings.
PMID- 25110765
TI - Noninvasive assessment of liver steatosis using ultrasound methods.
AB - Hepatic steatosis is a condition frequently encountered in clinical practice,
with potential progression towards chirrhosis and hepatocellular carcinoma.
Ultrasonography (US) is one of the noninvasive imaging techniques used in the
diagnosis of steatosis. We will review the US diagnostic criteria, the US
performance in the diagnosis and grading of hepatic steatosis, the US steatosis
models, but also its limitations in the diagnosis of steatosis. In addition, we
will discuss 2 modern methods of assessing hepatic steatosis using ultrasounds,
namely the computerized processing of data forming the US image and the
controlled attenuation parameter measured with unidimensional transient
elastography.
PMID- 25110766
TI - Ultrasound guided axillary brachial plexus block.
AB - The axillary brachial plexus block is the most widely performed upper limb block.
It is relatively simple to perform and one of the safest approaches to brachial
plexus block. With the advent of ultrasound technology, there is a marked
improvement in the success rate of the axillary block. This review will focus on
the technique of ultrasound guided axillary brachial plexus block.
PMID- 25110767
TI - How can the use of lung ultrasound in cardiac arrest make ultrasound a holistic
discipline. The example of the SESAME-protocol.
AB - The most critical application of critical ultrasound - cardiac arrest - is the
opportunity for technical considerations. The necessity to immediately detect
reversible causes is integrated in the concept of holistic ultrasound. Holistic
ultrasound is defined as a discipline where each element interacts with the
others, and where the understanding of each of them allows understanding the
whole. A narrow machine (not necessarily a laptop), a fast start-on time, a
simple keyboard highlighting three useful buttons, a universal microconvex probe
able to immediately detect pneumothorax, then deep venous thrombosis, then
abdominal bleeding, then pericardial tamponade, then cardiac anomalies will allow
a fast protocol. The concept of holistic ultrasound is particularly on focus in
the first step done at the lung (search for pneumothorax and clearance for fluid
therapy), since the best image is obtained with the simplest equipment devoid of
traditional facilities (image filtering, harmonics, time lag, Doppler...). The
same simple gray-scale equipment is used for the other steps, all what is needed
is to see the real-time image of what is facing the probe: the very principle of
visual medicine. The same approach can be used with no change, just more quietly,
for many less urgent settings.
PMID- 25110768
TI - The role of ultrasound in the imaging assessment of the augmented breast. A
pictorial review.
AB - The imaging evaluation of the augmented breast is becoming more and more frequent
in daily practice. Even if mammography remains the golden standard for breast
cancer screening, ultrasound is used as a first step investigation in young
symptomatic patients or as a screening tool in detecting pathology related to the
implants. This pictorial essay reviews the indications and limitations of the
imaging methods and illustrates the normal and pathological ultrasound findings
in the augmented breast.
PMID- 25110769
TI - Fournier's gangrene. Case report.
AB - Fournier's gangrene is a condition marked by fulminant polymicrobial necrotizing
fasciitis of the urogenital and perineal areas. We present a patient with
Fournier's gangrene and describe the physical examination and bedside sonographic
findings. These findings can assist in the evaluation of patients with concerning
symptoms so there can be timely administration of antibiotics and specialist
consultation when necessary.
PMID- 25110770
TI - Bilateral subclavian steal syndrome in an intensive care unit. A case report.
AB - We report the case of a 56-year-old man who presented with arterial hypotension,
lightheadedness, vomiting, a sense of tingling in his right arm, and a right
beating horizontal nystagmus. He was initially admitted to the Intensive care
unit and treated with standard vasopressor agents. A neurosonological examination
showed the steal phenomenon on both vertebral arteries; the neuroradiological
examination revealed occlusion of the left subclavian artery and subtotal
stenosis of the innominate artery. Percutaneous transluminal angioplasty was
performed. Our case demonstrates how bilateral subclavian steal syndrome should
be taken into account in the case of a seemingly hypotensive patient unresponsive
to standard therapy.
PMID- 25110771
TI - Cutaneous histiocytoma - histological and imaging correlations. A case report.
AB - Dermatofibroma (benign fibrous histiocytoma) represents one of the most common
skin tumors. We present the case of a 52 year old female patient with a highly
pigmented nodular lesion, localized on the right thigh. Dermoscopy completed the
clinical diagnosis, but could not exclude a malignant tumour . Ultrasound
examination (Dermascan C sonograms 20 MHz, 2D ultrasound, Doppler ultrasound,
contrast enhanced ultrasound, and elastography) evidenced a highly vascularized
lesion (peripheral type of vascularization), and a sonographic depth index of 8.3
mm. The histopathological examination confirmed the diagnosis of a benign fibrous
histiocytoma with the histological Breslow index of 8 mm. The particularity of
the case consists of the complex non-invasive and in real time imaging
examination which describes the "in vivo" histology of the benign tumor lesion.
PMID- 25110772
TI - Contrast enhanced ultrasound of a hepatic soft tissue angiosarcoma metastasis.
Case report.
AB - Diagnostic imaging of angiosarcoma and angiosarcoma metastasis has been described
as confusing and challenging. We present a rare case of hepatic soft tissue
angiosarcoma metastasis, which was diagnosed by contrast enhanced ultrasound
(CEUS). The case further exemplifies the ability of CEUS to solve discrepancies
between other imaging modalities.
PMID- 25110773
TI - Diagnosis of sacrococcygeal teratoma using two and three-dimensional
ultrasonography: two cases reported and a literature review.
AB - The occurrence of a fetal tumor is rare, 50% of all fetal tumors being
sacrococcygeal teratomas. Prenatal diagnosis of this condition is important for
the monitoring of the affected fetuses and for establishing the mode and time of
delivery. We describe two cases of fetal sacrococcygeal teratoma diagnosed by 2D-
and 3D-ultrasound. Three-dimensional ultrasound proved to be useful both in the
diagnosis and patient counseling. The combination of 2D- and 3D-ultrasound
enables the diagnosis to be made during the first trimester of pregnancy.
PMID- 25110774
TI - Efficient enrichment of glycopeptides using metal-organic frameworks by
hydrophilic interaction chromatography.
AB - Selective enrichment of glycopeptides from complicated biological samples is
critical for glycoproteomics to obtain the structure and glycosylation
information of glycoproteins using mass spectrometry (MS), which still remains a
great challenge. Hydrophilic interaction chromatography (HILIC)-based strategies
have been proposed for selective isolation of glycopeptides via the interactions
between the glycan of glycopeptides and the matrices. However, the application of
these methods is limited by the medium selectivity of HILIC matrices. In this
study, hydrophilic metal-organic frameworks (MOFs) were fabricated and used as a
HILIC matrix. The cross-linked CD-MOFs (LCD-MOFs) were facilely prepared with
gamma-cyclodextrin as ligand and possessed nano-sized cubic structure, superior
hydrophilicity, and bio-compatibility. The LCD-MOFs performance for the selective
enrichment of glycopeptides from the complex biological samples were investigated
with a digested mixture of human immunoglobulin G (IgG) that was used as standard
samples. In the selectivity assessment, the non-glycopeptides causing ion
suppression to the glycopeptides were effectively removed, the signal of
glycopeptides were enhanced significantly by LCD-MOFs, and twenty glycopeptides
were identified with 67 fmol of IgG digest. In addition, the resulting LCD-MOFs
demonstrated the lower detection limit (3.3 fmol) with a satisfactory recovery
yield (84-103%) for glycopeptide enrichment from a digest of IgG. Furthermore, a
promising protocol was developed for the selective enrichment of glycopeptides
from mouse liver, and 344 unique N-glycosylation sites that mapped to 290
different glycoproteins were identified in a single MS run. The results clearly
demonstrated that when used in a HILIC matrix, LCD-MOFs have great potential for
identifying and enriching low-abundant glycopeptides in complex biological
samples.
PMID- 25110775
TI - Reply: To PMID 24762147.
PMID- 25110776
TI - Assessment of the effect of the climate variations of coastal surface water and
study of Sepia officinalis spawing.
AB - The aim of this study was to establish whether climate change affected migratory
behaviour of Sepia officinalis (Linnaeus, 1758), which is an important resource
for small-scale fishermen of Abruzzo region (Italy). Starting at the beginning of
March until the end of April, the cuttlefish in this area migrates from deep cold
water towards warmer coastal waters, where they spawn. Small-scale fishing of
cuttlefish is permitted in costal waters from March to September. During the
study period, between March and September 2008, both cuttlefish traps and trammel
nets were used in 5 sampling areas along the Abruzzo coast to test their relative
efficiency in catching cuttlefish. Trapped specimens were counted, weighed and
measured, their gender and sexual maturity were also determined. The data
obtained from the sampling were correlated to surface water temperature to assess
possible changes in migration behaviours. The obtained data show that during the
first months of migration (March and April), a greater percentage of large males
was caught, while females and smaller males predominated later in the year. The
study also showed that surface water temperature did not reveal any significant
shifts from the trend over the last 10 years. As for the efficiency of the
fishing methods, traps were found to be more effective than trammel nets.
PMID- 25110777
TI - Collaboration through competition.
PMID- 25110778
TI - The author file: Andrew Straw.
PMID- 25110779
TI - Points of significance: Analysis of variance and blocking.
PMID- 25110780
TI - The human proteome takes the spotlight.
PMID- 25110781
TI - Visualizing voltage.
PMID- 25110782
TI - More specific CRISPR editing.
PMID- 25110783
TI - Cancer stem cells on demand.
PMID- 25110784
TI - The sobering reality of outcomes when older adults require prolonged mechanical
ventilation.
PMID- 25110785
TI - Author response.
PMID- 25110786
TI - Author response.
PMID- 25110787
TI - Letter to the editor: resident presentations at scientific meetings.
PMID- 25110788
TI - Embodiment without bodies? Analysis of embodiment in US-based pro-breastfeeding
and anti-male circumcision movements.
AB - This article uses the cases of pro-breastfeeding and anti-circumcision activism
to complicate the prevailing conceptualisation of embodiment in research on
embodied health movements (EHMs). Whereas most EHM activists draw on their own
bodily experiences, in the breastfeeding and circumcision movements, embodiment
by proxy is common. Activists use embodiment as a strategy but draw on physical
sensations that they imagine for other people's bodies, rather than on those they
experience themselves. Pro-breastfeeding activists, who seldom disclose whether
they were themselves breastfed, target mothers, encouraging them to breastfeed
rather than to formula feed their children in order to reduce their child's risk
of disease. Anti-circumcision activists, only some of whom are circumcised men,
urge parents to leave their sons' penises intact in order to avoid illness and
disfigurement and to preserve the sons' rights to make their own informed
decisions as adults. In both movements activists use embodiment as a persuasive
strategy even though they themselves do not necessarily embody the risks of the
negative health outcomes with which they are concerned. Future research on EHMs
should reconceptualise EHMs to include embodiment by proxy and examine whether
this important phenomenon systematically affects movement strategies and
outcomes.
PMID- 25110789
TI - Careful science? Bodywork and care practices in randomised clinical trials.
AB - Concern about obesity has prompted numerous public health campaigns that urge
people to be more physically active. The campaigns often include normative
statements and attempt to impose restrictions on individuals' lives without
considering the complexities of daily life. We suggest that broadening the focus
to reflect everyday practices would foster better targeted public health
campaigns. This article is based on our participation in FINE, a
multidisciplinary Danish research project. The core methodology of FINE was a
randomised controlled trial in which 61 moderately overweight men were put into
different exercise groups. In this article we analyse the scientific work of the
trial as representing entangled processes of bodywork, where data are extracted
and objectified bodies are manipulated and care practices address the emotional,
social and mundane aspects of the participants' everyday lives. Care practices
are an inherent part of producing scientific facts but they are removed from the
recognised results of scientific practice and thus from common public health
recommendations. However, knowledge about the strategic use of care practices in
lifestyle interventions is important for public health initiatives and future
efforts should incorporate this aspect.
PMID- 25110790
TI - Constructing notions of healthcare productivity: the call for a new
professionalism?
AB - Improving performance is an imperative for most healthcare systems in
industrialised countries. This article considers one such system, the UK's
National Health Service (NHS). Recent NHS reforms and strategies have advocated
improved healthcare productivity as a fundamental objective of policy and
professional work. This article explores the construction of productivity in
contemporary NHS discourse, analysing it via the Foucauldian concept of
governmentality. In this manner it is possible to investigate claims that the
commodification of health work constitutes a threat to autonomy, and counter that
with an alternative view from a perspective of neoliberal self-governance.
Contemporary policy documents pertaining to NHS productivity were analysed using
discourse analysis to examine the way in which productivity was framed and how
responsibility for inefficient resource use, and possible solutions, were
constructed. Data reveals the notion of productivity as problematic, with
professionals as key protagonists. A common narrative identifies traditional NHS
command/control principles as having failed to engage professionals or having
been actively obstructed by them. In contrast, new productivity narratives are
framed as direct appeals to professionalism. These new narratives do not support
deprofessionalisation, but rather reconstruct responsibilities, what might be
called 'new professionalism', in which productivity is identified as an
individualised professional duty.
PMID- 25110791
TI - Response to McDermott.
PMID- 25110792
TI - Response to Hiatt et al.
PMID- 25110793
TI - Buccal mucosal graft in reconstructive urology: uses beyond urethral stricture.
AB - The use of buccal mucosal grafts for the reconstruction of urethral strictures is
an established procedure. Because of its robustness, the buccal mucosal graft
could also potentially provide an alternative for other indications in
reconstructive urology. We report here six consecutive patients who received a
buccal mucosal graft for ureteral strictures, glans reconstruction and stoma
stenosis. The follow up for all patients ranged from 26 to 50 months. The buccal
mucosal graft showed excellent functional results for the ureteral strictures and
stenosis from ureterocutaneostomy. For glans reconstructions, the buccal mucosal
grafts delivered excellent cosmetic and functional results without causing meatal
stenosis. We conclude the buccal mucosal graft can be used in reconstructive
surgery beyond the reconstruction of urethral strictures.
PMID- 25110794
TI - Editorial comment to buccal mucosal graft in reconstructive urology: uses beyond
urethral stricture.
PMID- 25110795
TI - Stent-assisted coil embolization--response.
PMID- 25110796
TI - Lamina terminalis fenestration--response.
PMID- 25110797
TI - Internal carotid artery anterior wall aneurysms--response.
PMID- 25110798
TI - The health of healthcare, Part V: Is the very freedom of providers at risk?
AB - When healthcare is fully compliant with the Patient Protection and Affordable
Health Care Act, U.S. health care providers lose their one inalienable American
right, namely freedom, and can no longer fulfill their fiduciary responsibility
to patients.
PMID- 25110799
TI - Eating small: applications and implications for nano-technology in agriculture
and the food industry.
PMID- 25110800
TI - Oncology medical home study examines physician payment models.
PMID- 25110801
TI - Utility of genetic testing linked to clinical interpretation.
PMID- 25110802
TI - Gum chewing: is it helpful or harmful?
PMID- 25110804
TI - Mercury ion responsive wettability and oil/water separation.
AB - A novel Hg(2+) responsive oil/water separation mesh with poly(acrylic acid)
hydrogel coating is reported. The mesh can separate oil and water because of the
superhydrophilicity of the poly(acrylic acid) hydrogel coating on the mesh, and
switch the wettability based on the chelation between Hg(2+) and poly(acrylic
acid) . The reversible change in oil contact angle of as-prepared mesh is about
149 degrees after immersion in Hg(2+) solution. This mesh is an ideal candidate
for oil-polluted water purification, especially for water that contains Hg(2+)
contaminant.
PMID- 25110805
TI - Increased serum heme oxygenase-1 levels as a diagnostic marker of oxidative
stress in preeclampsia.
AB - OBJECTIVE: To evaluate the utility of serum biomarkers in the diagnosis of
preeclampsia (PE) and also investigate possible correlation with pathogenesis of
PE. METHODS: Maternal serum concentrations of heme oxygenase-1 (HO1) and N-myc
downstream-regulated gene 1 (NDRG1) were measured at 27-34 weeks of gestation in
a case-control study of 33 pregnant women diagnosed with PE and in 43
normotensive pregnant women without proteinuria. The Mann-Whitney U test and
Spearman's correlation were used for statistical analysis. RESULTS: The median
serum HO1 level was found to be significantly higher in the PE group [76.7 ng/ml
(23.4-445.7)] than control group [55.9 ng/ml (3.7-354.3)] (p = 0.006). Positive
correlation was found between HO1 levels with presence of PE (r = 0.316, p =
0.005). There was no significant difference in NDRG1 values between the two
groups (p = 0.226). CONCLUSIONS: Serum HO1 levels were found to be increased in
patients with PE compared with normotensive pregnant women.
PMID- 25110806
TI - Synthesis and fungistatic activity of bicyclic lactones and lactams against
Botrytis cinerea, Penicillium citrinum, and Aspergillus glaucus.
AB - Six analogues of natural trans-4-butyl-cis-3-oxabicyclo[4.3.0]nonan-2-one (3) and
three derivatives, 11, 12, and 13, of Vince lactam (10) were synthesized and
tested as fungistatic agents against Botrytis cinerea AM235, Penicillium citrinum
AM354, and six strains of Aspergillus. Moreover, bioresolution carried out by
means of whole cell microorganisms and commercially available enzymes afforded
opposite enantiomerically enriched (-) and (+) isomers of Vince lactam (10),
respectively. The effect of compound structures and stereogenic centers on
biological activity has been discussed. The highest fungistatic activity was
observed for four lactones: 3, 4, 7, and 8 (IC50 = 104.6-115.2 MUg/mL) toward B.
cinerea AM235. cis-5,6-Epoxy-2-aza[2.2.1]heptan-3-one (13) indicated significant
fungistatic activity (IC50 = 107.1 MUg/mL) against Aspergillus glaucus AM211.
trans-4-Butyl-cis-3-oxabicyclo[4.3.0]nonan-2-one (3) and trans-4-butyl-cis-3
oxabicyclo[4.3.0]non-7-en-2-one (7) exhibited high fungistatic activity (IC50 =
143.2 and 110.2 MUg/mL, respectively) against P. citrinum AM354 as well.
PMID- 25110807
TI - Pulsed magnetic field induced fast drug release from magneto liposomes via
ultrasound generation.
AB - Fast drug delivery is very important to utilize drug molecules that are short
lived under physiological conditions. Techniques that can release model molecules
under physiological conditions could play an important role to discover the
pharmacokinetics of short-lived substances in the body. Here an experimental
method is developed for the fast release of the liposomes' payload without a
significant increase in (local) temperatures. This goal is achieved by using
short magnetic pulses to disrupt the lipid bilayer of liposomes loaded with
magnetic nanoparticles. The drug release has been tested by two independent
assays. The first assay relies on the AC impedance measurements of MgSO4 released
from the magnetic liposomes. The second standard release assay is based on the
increase of the fluorescence signal from 5(6)-carboxyfluorescein dye when the dye
is released from the magneto liposomes. The efficiency of drug release ranges
from a few percent to up to 40% in the case of the MgSO4. The experiments also
indicate that the magnetic nanoparticles generate ultrasound, which is assumed to
have a role in the release of the model drugs from the magneto liposomes.
PMID- 25110808
TI - Effect of astaxanthin on cataract formation induced by glucocorticoids in the
chick embryo.
AB - PURPOSE: To examine whether astaxanthin (AST) prevent the cataract formation
induced by glucocorticoid in chick embryo. MATERIALS AND METHODS: Hydrocortisone
hemisuccinate sodium (HC) (0.5 MUmol/egg) was administered directly into the air
chamber in the egg shell of chick embryo day 15. The eggs were then kept in an
incubator at same conditions and administered 100 MUL of 50 (HC + AST50 group),
80 (HC + AST80 group), 100 (HC + AST100 group) mg/mL of AST solutions dissolved
in dimethyl sulfoxide (DMSO) 3 h after administration of HC. In addition, non-HC
treated group (treated with physiological saline without HC and 100 MUL of DMSO),
HC-alone group (treated with 0.5 MUmol of HC and 100 MUL of DMSO), and AST100
group (treated with physiological saline without HC and 100 MUL of DMSO) were
also incorporated. After 48 h of treatment, lenses were removed from embryo and
classified into five stages according to developed opacity. The amounts of
reduced glutathione in the lenses and the blood glucose levels were measured.
RESULTS: The average scores of lens opacitiy were 2.63 +/- 1.02 nmol/lens (HC
alone), 2.78 +/- 0.97 nmol/lens (HC + AST50), 2.22 +/- 1.20 nmol/lens (HC +
AST80) and 1.84 +/- 0.83 nmol/lens (HC + AST100; p < 0.05), respectively.
Administration of AST decreased the lens opacity dose-dependently. The amounts of
reduced glutathione in lenses were 11.6 +/- 2.8 nmol/lens (HC-alone), 11.3 +/-
2.7 nmol/lens (HC + AST50), 13.4 +/- 2.4 nmol/lens (HC + AST80) and 13.7 +/- 3.1
nmol/lens (HC + AST100; p < 0.05), respectively. Higher levels of AST prevented
loss of reduced glutathione from the lens. CONCLUSION: These findings support
that AST protects glucocorticoid-induced cataract in chick embryo.
PMID- 25110809
TI - Efficacy of carbonaceous materials for sorbing polychlorinated biphenyls from
aqueous solution.
AB - Interest in incorporating nanomaterials into water treatment technologies is
steadily growing, driving the necessity to understand the interaction of these
new materials with specific water contaminants. In the present study, five
different carbonaceous materials: activated carbon (AC), charcoal (BC), carbon
nanotubes (CNT), graphene (GE), and graphene oxide (GO) were investigated as
sorbent materials for 11 polychlorinated biphenyl (PCB) congeners in aqueous
concentrations in the pg-MUg/L range. Sorbent-water distribution coefficients
(Ks) calculated in aqueous concentrations of ng/L show that AC is superior to GE,
GO, CNT, and BC for the 11 PCB congeners investigated by an average of 1.1, 1.1,
1.3, and 2.5 orders of magnitude, respectively. Additionally, maximum capacity
and sorption affinity parameters from the Langmuir, Freundlich, and Polanyi
Dubinin-Manes (PDM) models show a similar result. Interestingly, however, the
effect of molecular planarity has greater impact on PCB sorption to the
nanomaterials, such that the planar congeners form stronger bonds with CNT, GE,
and GO compared to AC and BC. This work demonstrated superior PCB sorption by AC
as compared with the nanomaterials examined such that substantial post production
modifications would be necessary for the nanomaterials to out-perform AC.
PMID- 25110810
TI - Component-controllable WS(2(1-x))Se(2x) nanotubes for efficient hydrogen
evolution reaction.
AB - Owing to the excellent potential for fundamental research and technical
applications in optoelectronic devices and catalytic activity for hydrogen
evolution reaction (HER), transition metal dichalcogenides have recently
attracted much attention. Transition metal sulfide nanostructures have been
reported and demonstrated promising application in transistors and
photodetectors. However, the growth of transition metal selenide nanostructures
and their applications has still been a challenge. In this work, we successfully
synthesized high-quality WSe2 nanotubes on carbon fibers via selenization. More
importantly, through optimizing the growth conditions, ternary WS2(1-x)Se2x
nanotubes were synthesized and the composition of S and Se can be systematically
controlled. The as-grown WS2(1-x)Se2x nanotubes on carbon fibers, assembled as a
working electrode, revealing low overpotential, high exchange current density,
and small series resistance, exhibit excellent electrocatalytic properties for
hydrogen evolution reaction. Our study provides the experimental groundwork for
the synthesis of low-dimensional transition metal dichalcogenides and may open up
exciting opportunities for their application in electronics, photoelectronics,
and catalytic electrochemical reactions.
PMID- 25110811
TI - Stability of the cationic oxidation states in Pr(0.50)Sr(0.50)CoO3 across the
magnetostructural transition by X-ray absorption spectroscopy.
AB - The possible hybridization between Pr 4f and O 2p states in Pr(0.50)Sr(0.50)CoO3
at low temperatures was investigated by different techniques. First, using
neutron diffraction we observed a strong contraction of some Pr-O bonds across
the magnetostructural transition at T(S) ~ 120 K. In contrast to the Pr-O bond
contraction in Pr(0.50)Sr(0.50)CoO3, this transition is not accompanied by the
appearance of Pr(4+) at low temperatures, as revealed by X-ray absorption
spectroscopy at Pr edges. Despite the fact that a Pr valence change is not the
mechanism that drives this transition, we point out an active participation of Pr
ions across T(S). Moreover, Co L(2,3)-edge and O K edge X-ray absorption spectra
did not reveal any spin-state variation and showed the stability of the average
formal valence of cobalt ions. The large density of empty t(2g) symmetry states
in the studied thermal range does not suggest the occurrence of Co(3+) in a pure
low-spin state. The overall metallic behavior agrees with our findings. We
propose a mixture of Co(3+) ions in the intermediate-spin or high-spin
configuration together with Co(4+) ions in a low- or intermediate-spin state.
PMID- 25110812
TI - A novel method to identify fat malabsorption: the Serum Retinyl Palmitate Test.
AB - BACKGROUND: Malabsorptive etiologies of chronic diarrhea are important to
identify. The 72-h stool for fecal fat test (FFT), the gold standard for
diagnosing fat malabsorption, is fraught with limitations that impact its
reliability. Vitamin A, a fat-soluble vitamin, parallels the absorption of
lipids. We assessed the feasibility and validate a novel clinical test, retinyl
palmitate (RP), for the diagnosis of fat malabsorption, and to compare the
results to the FFT. METHODS: Using a case-control study design, patients with
chronic diarrhea secondary to suspected malabsorption, and healthy control
subjects were identified. A Dietitian taught subjects to consume a 100g fat diet
for the FFT with measurements of stool fat after 72-h. Serum levels of Vitamin A
(retinol) and RP were measured by reversed-phase high pressure liquid
chomatography. Two-way comparisons were made between the groups using 2 sample
Wilcoxon rank-sum tests. RESULTS: Sixteen patients completed this study (8 cases
and 8 control subjects). Fecal fat results were available for 15/16 patients. The
sensitivity of the FFT was 100% (identified all cases), but the FFT specificity
was 42%, as 4/7 control patients were identified as malabsorbers. Cases with
short bowel syndrome had the lowest RP levels but this did not meet statistical
significance. There was no significant difference for serum RP levels when
comparing cases and control patients' AUC. CONCLUSIONS: Serum RP is useful to
identify malabsorption, albeit in severe cases. Furthermore, we have shown that
the 72-hour FFT has poor performance characteristics, highlighting the need for
more useful diagnostics in identifying malabsorption.
PMID- 25110813
TI - Performance enhancement in the measurement of 5 endogenous steroids by LC-MS/MS
combined with differential ion mobility spectrometry.
AB - BACKGROUND: Challenges for steroid analysis by LC-MS/MS include low ionization
efficiency, endogenous isobars with similar fragmentation patterns and
chromatographic retention. Differential ion mobility spectrometry (DMS) provides
an additional degree of separation prior to MS/MS detection, and shows promise in
improving specificity of analysis. We developed a sensitive and specific method
for measurement of corticosterone, 11-deoxycortisol, 11-deoxycorticosterone, 17
hydroxyprogesterone and progesterone in human serum and plasma using an ABSciex
5500 mass spectrometer equipped with a differential ion mobility interface.
METHODS: 250MUL aliquots of serum were spiked with deuterated internal standards
and extracted with MTBE. The samples were analyzed using positive mode
electrospray LC-DMS-MS/MS. The method was validated and compared with
immunoassays and LC-MS/MS methods of reference laboratories. RESULTS: Inter and
intra assay imprecision was <10%. Limits of quantification and detection in
nmol/L were 0.18, 0.09 for corticosterone and 17-hydroxyprogesterone, 0.30, 0.16
for 11-deoxycortisol, 0.12, 0.06 for progesterone and 0.06, 0.03 for 11
deoxycorticosterone. Comparison for progesterone and 17-hydroxyprogesterone with
immunoassay showed slopes of 0.97 and 1.0, intercepts of 0.16 and 0.10 and
coefficients of determination (r(2)) of 0.92 and 0.97, respectively. Progesterone
by immunoassay showed positive bias in samples measuring <3.18nmol/L. Reference
intervals for progesterone and 11-deoxycorticosterone in post-menopausal women
were found to be <2.88 and <0.28nmol/L respectively. CONCLUSIONS: We developed
and validated an LC-DMS-MS/MS method for analysis of five endogenous steroids
suitable for routine measurements in clinical diagnostic laboratories.
Specificity gained with DMS allows reducing the complexity of sample preparation,
decreasing LC run times and increasing speed of the analysis.
PMID- 25110814
TI - Application of nuclear magnetic resonance spectroscopy for identification of
ciprofloxacin crystalluria.
AB - This is a report describing a previously healthy young patient, who experienced
crystalluria and non-cholestatic acute liver injury after a single intravenous
dose of 400mg. The nuclear magnetic resonance spectra confirmed that the urinary
sediment in our patient was formed by pure ciprofloxacin. The nuclear magnetic
resonance spectra ((1)H NMR) of the urine sediment are a good test to confirm the
composition of the crystals observed by electron microscopy and infrared
spectrum. The findings indicate the importance of adequate hydration, urinalysis,
measurement of pH and liver enzyme levels, prior to treatment with ciprofloxacin.
Our findings also indicate that ciprofloxacin should not be administered to
patients with renal tubular acidosis, due to their high urinary pH.
PMID- 25110815
TI - Assessment of the reproducibility of oligoclonal IgM band detection for its
application in daily clinical practice.
AB - BACKGROUND: The presence of oligoclonal IgM bands (OCMB) in cerebrospinal fluid
(CSF) is an unfavourable prognostic marker in multiple sclerosis. There is no
commercial test to investigate OCMB status. However, a sensitive and specific
isoelectrofocusing (IEF) and western blot method was described. We aimed to study
the inter-centre reproducibility of this technique, a necessary condition for a
reliable test to be incorporated into clinical practice. METHODS: The presence of
OCMB was analysed by IEF and western blot with prior reduction of pentameric IgM.
We assayed the reproducibility of this test in a blinded multicentre study
performed in 13 university hospitals. Paired-CSF and serum samples from 52
neurological patients were assayed at every centre. RESULTS: Global analysis
rendered a concordance of 89.8% with a kappa value of 0.71. CONCLUSION: These
data indicate that OCMB detection by means of IEF and western blot with IgM
reduction shows a good interlaboratory reproducibility and thus can be used in
daily clinical setting.
PMID- 25110816
TI - Spontaneous neural activity alterations in temporomandibular disorders: a cross
sectional and longitudinal resting-state functional magnetic resonance imaging
study.
AB - The involvement of the central nervous system in the pathophysiology of
temporomandibular disorders (TMD) has been noticed. TMD patients have been shown
dysfunction of motor performance and reduced cognitive ability in
neuropsychological tests. The aim of this study is to explore the spontaneous
neural activity in TMD patients with centric relation (CR)-maximum intercuspation
(MI) discrepancy before and after stabilization splint treatment. Twenty-three
patients and twenty controls underwent clinical evaluations, including CR-MI
discrepancy, Helkimo indices and chronic pain, and resting state functional
magnetic resonance imaging scans at baseline. Eleven patients repeated the
evaluations and scanning after the initial wearing (T1) and 3months of wearing
(T2) of the stabilization splint. The fractional amplitude of low-frequency
fluctuation (fALFF) was calculated to compare the neural functions. At baseline,
the patients showed decreased fALFF in the left precentral gyrus, supplementary
motor area, middle frontal gyrus and right orbitofrontal cortex compared with the
controls (P<0.05, AlphaSim corrected). Negative correlations were found between
the fALFF in the left precentral gyrus and vertical CR-MI discrepancy of
bilateral temporomandibular joints of patients (P<0.05, two-tailed). At T2, the
symptoms and signs of the patients were improved, and a stable condylar position
on the CR was recovered, with increased fALFF in the left precentral gyrus and
left posterior insula compared with pretreatment. The fALFF decrease in the
patients before treatment was no longer evident at T2 compared with the controls.
The results suggested that TMD patients with CR-MI discrepancy showed
significantly decreased brain activity in their frontal cortexes. The
stabilization splint elicited functional recovery in these cortical areas. These
findings provided insight into the cortical neuroplastic processes underlying TMD
with CR-MI discrepancy and the therapeutic mechanisms of stabilization splint.
PMID- 25110817
TI - Promoting national blood systems in developing countries.
AB - PURPOSE OF REVIEW: Over the last decade, there has been increased global
attention dedicated to improving the availability, safety and use of blood in low
income and middle-income countries. These efforts have focused on a number of
common objectives, such as establishing a 100% voluntary nonremunerated blood
donor base and implementing component therapy. Recently, some of these objectives
have been challenged. This article reviews many recent findings of the experts
leading these international projects. RECENT FINDINGS: The majority of current
research is focused on blood donation and patient blood management in sub-Saharan
Africa, with contributions to other fields of blood safety in Latin America, the
Caribbean and Asia. Countries collecting blood from the replacement donors are
challenging the notion that replacement donors are inherently a higher risk group
than voluntary donors. Simultaneously, many countries are considering how best to
improve the management of their blood inventories and to optimize their national
standards, guidelines and protocols - all with the goal of improving patient
outcomes. SUMMARY: There still exist many questions in the areas of blood
donation and clinical use that are either unanswered or merit further
investigation. Given the variable circumstances observed between different
countries and geographic regions, it sometimes may be advisable to limit global
recommendations in favor of the regionally focused ones.
PMID- 25110818
TI - Catalytic generation of vinylthionium ions. (4 + 3)-Cycloadditions and Friedel
Crafts alkylations.
AB - A 3-phenylsulfanyl-substituted allylic alcohol and an ester thereof were treated
with Bronsted acids or a gold catalyst, respectively, to generate vinylthionium
ions. These species react with dienes, primarily substituted furans, to give
products of either (4 + 3)-cycloaddition or Friedel-Crafts alkylation. The
results are rationalized on the basis of a stepwise mechanism in which the
relative rates of ring closure versus proton loss in the intermediate sigma
complex determine the course of the reaction.
PMID- 25110819
TI - Incidence of and risk factors for involvement of the central nervous system in
acute myeloid leukemia.
AB - It is thought that the low incidence of central nervous system (CNS) involvement
in acute myeloid leukemia (AML) does not justify routine CNS prophylaxis, as high
dose cytarabine eliminates CNS disease. To investigate whether chemotherapy that
does not include high-dose cytarabine increases the risk of CNS involvement, the
medical records of 1412 newly diagnosed patients with AML were reviewed. In 1370
patients, lumbar puncture (LP) was performed only if clinically indicated, and
CNS disease was detected in 45 (3.3%) patients. Another 42 patients underwent
routine LP as part of an investigational protocol, and in eight (19%) CNS disease
was detected (p < 0.0001). Risk factors included high lactate dehydrogenase,
African-American ethnicity and young age. Patients receiving high-dose cytarabine
and those who did not had similar rates of CNS involvement. Disease-free survival
(DFS) and overall survival were shorter in patients with CNS involvement. It
remains to be determined whether routine CNS prophylaxis would improve DFS.
PMID- 25110820
TI - Pharmacogenetic studies in children with acute lymphoblastic leukemia in
Argentina.
AB - The aim of this study was to evaluate the influence of the most common genetic
variants in methylenetetrahydrofolate reductase (MTHFR), thiopurine
methyltransferase (TPMT) and glutathione-S-transferases (GSTs) on the outcome of
acute lymphoblastic leukemia (ALL) treatment in Argentinean children. Two hundred
and eighty-six patients with ALL treated with two Berlin-Frankfurt-Munster (BFM)
based protocols were analyzed. Ten genetic variants were studied. Toxicity was
evaluated during the consolidation phase. Children who received 2 g/m(2)/day of
methotrexate and carried at least one 677T allele in MTHFR showed an increased
risk of developing severe leukopenia (p = 0.004) and neutropenia (p = 0.003).
Intermediate-risk (IR) patients with a heterozygous TPMT genotype had a higher
probability of event-free survival than those with a wild-type genotype.
Genotyping of MTHFR polymorphisms might be useful to optimize consolidation
therapy, reducing the associated severe hematologic toxicity. Further studies are
necessary to establish the usefulness of MTHFR and TPMT variants as additional
markers to predict outcome in the IR group.
PMID- 25110821
TI - Hepatitis B virus infection correlates with poor prognosis of extranodal natural
killer/T cell lymphoma.
AB - Studies have shown that hepatitis B virus (HBV) infection may play an important
role in the lymphomagenesis of lymphoma, but no studies regarding the
relationship between HBV infection and extranodal natural killer/T cell lymphoma
(ENKTL) have been reported previously. One hundred and seven patients diagnosed
with ENKTL were retrospectively reviewed. The hepatitis B surface antigen (HBsAg)
positive rate was 13.1%, and no significant correlation existed between HBV
infection and clinical characteristics (p > 0.05). No significant difference
existed in complete remission rate between HBsAg-positive and -negative groups
(42.9% vs. 44.1%, p = 1.000). In a multivariate Cox regression model that
included international prognostic index (IPI) score, induction chemotherapy
regimen and HBsAg status, all these variables were independent prognostic factors
for overall survival (OS) and progression-free survival (PFS) (p < 0.05). In
conclusion, the HBsAg-positive rate in ENKTL was similar to that of the normal
population in a high HBV endemic area, and HBsAg-positive status was an
independent prognostic factor for OS and PFS.
PMID- 25110822
TI - Underlying autoimmune diseases are not aggravated during treatment with
lenalidomide in patients with mucosa-associated lymphoid tissue lymphoma:
author's reply.
PMID- 25110823
TI - Aggressive congenital juvenile myelomonocytic leukemia associated with somatic
KRAS p.G13D mutation and concurrent germline IGF1R duplication.
PMID- 25110824
TI - Extended treatment with brentuximab vedotin in patients with relapsed or
refractory CD30-positive hematological malignancies.
PMID- 25110825
TI - Comprehensive geriatric assessment is an essential tool to support treatment
decisions in elderly patients with diffuse large B-cell lymphoma: a prospective
multicenter evaluation in 173 patients by the Lymphoma Italian Foundation (FIL).
AB - We performed a multicenter study to validate the concept that a simple
comprehensive geriatric assessment (CGA) can identify elderly, non-fit patients
with diffuse large B-cell lymphoma (DLBCL) in whom curative treatment is not
better then palliation, and to analyze potential benefits of treatment modulation
after further subdividing the non-fit category by CGA criteria. One hundred and
seventy-three patients aged > 69 treated with curative or palliative intent by
clinical judgement only were grouped according to CGA into fit (46%), unfit (16%)
and frail (38%) categories. Two-year overall survival (OS) was significantly
better in fit than in non-fit patients (84% vs. 47%; p < 0.0001). Survival in
unfit and frail patients was not significantly different. Curative treatment
slightly improved 2-year OS in unfit (75% vs. 45%) but not in frail patients (44%
vs. 39%). CGA was confirmed as very efficient in identifying elderly patients
with DLBCL who can benefit from a curative approach. Further efforts are needed
to better tailor therapies in non-fit patients.
PMID- 25110826
TI - Cyclic and acyclic fructose conformers in the gas phase: a large-scale second
order perturbation theory study.
AB - We performed large-scale second-order perturbation theory gas-phase calculations
to study about five hundred structures of D-fructose. The two lowest energy
fructose structures identified are beta-pyranoses possessing (2)C5 chair, with
DeltaG(298 K) of 6 kJ/mol, differing in orientation of the equatorially
positioned hydroxymethyl group, gt and g'g, where the gt rotamer is the global
minimum, consistent with the recent microwave spectroscopy study. We have found
that interconversions from the fructose global minimum to the second and third
most stable beta-pyranose rotamers involve the energy barriers of ca. 30 kJ/mol.
Among numerous fructofuranose conformers discovered (about 250), a pair of the
((3)T2) alpha- and (E3) beta-anomers are energetically most preferred and lie at
least 12 kJ/mol above the global minimum. We also found that the fructose open
chain structures lie significantly higher in energy than the most stable cyclic
species. The commonly used M06-2X density functional performs well compared to
MP2 and G4 theory at identifying the low-energy fructose minima, including the
global one, and at reproducing their intramolecular H-bond geometric parameters.
The lowest-energy gas-phase pyranose and furanose structures of fructose benefit
from stabilization due to the cooperative or quasi-linear H-bonding and both endo
and exo anomeric effects.
PMID- 25110827
TI - Antibody informatics for drug discovery.
AB - More and more antibody therapeutics are being approved every year, mainly due to
their high efficacy and antigen selectivity. However, it is still difficult to
identify the antigen, and thereby the function, of an antibody if no other
information is available. There are obstacles inherent to the antibody science in
every project in antibody drug discovery. Recent experimental technologies allow
for the rapid generation of large-scale data on antibody sequences, affinity,
potency, structures, and biological functions; this should accelerate drug
discovery research. Therefore, a robust bioinformatic infrastructure for these
large data sets has become necessary. In this article, we first identify and
discuss the typical obstacles faced during the antibody drug discovery process.
We then summarize the current status of three sub-fields of antibody informatics
as follows: (i) recent progress in technologies for antibody rational design
using computational approaches to affinity and stability improvement, as well as
ab-initio and homology-based antibody modeling; (ii) resources for antibody
sequences, structures, and immune epitopes and open drug discovery resources for
development of antibody drugs; and (iii) antibody numbering and IMGT. Here, we
review "antibody informatics," which may integrate the above three fields so that
bridging the gaps between industrial needs and academic solutions can be
accelerated. This article is part of a Special Issue entitled: Recent advances in
molecular engineering of antibody.
PMID- 25110828
TI - Lycopene attenuates insulin signaling deficits, oxidative stress,
neuroinflammation, and cognitive impairment in fructose-drinking insulin
resistant rats.
AB - Fructose intake is linked with the increasing prevalence of insulin resistance,
and insulin resistance links Alzheimer's disease with impaired insulin signaling,
oxidative damage, neuroinflammation, and cognitive impairment. As a member of the
carotenoid family of phytochemicals, lycopene is used as a potent free scavenger,
and has been demonstrated to be effective in anti-oxidative stress and anti
inflammatory reaction in the models of AD and other neurodegenerative diseases.
Here, we investigated the effect of lycopene on learning and memory impairment
and the possible underlying molecular events in fructose-drinking insulin
resistant rats. We found that long-term fructose-drinking causes insulin
resistance, impaired insulin signaling, oxidative stress, neuroinflammation, down
regulated activity of cholinergic system, and cognitive impairment, which could
be significantly ameliorated by oral lycopene administration. The results from
this study provide experimental evidence for using lycopene in the treatment of
brain damage caused by fructose-drinking insulin resistance.
PMID- 25110830
TI - Clinical effectiveness of interventions for treatment-resistant anxiety in older
people: a systematic review.
AB - BACKGROUND: Anxiety and related disorders include generalised anxiety disorder,
obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder and
phobic disorders (intense fear of an object or situation). These disorders share
the psychological and physical symptoms of anxiety, but each disorder has its own
set of characteristic symptoms. Anxiety disorders can be difficult to recognise,
particularly in older people (those aged over 65 years). Older people tend to be
more reluctant to discuss mental health issues and there is the perception that
older people are generally more worried than younger adults. It is estimated that
between 3 and 14 out of every 100 older people have an anxiety disorder. Despite
treatment, some people will continue to have symptoms of anxiety. People are
generally considered to be 'resistant' or 'refractory' to treatment if they have
an inadequate response or do not respond to their first treatment. Older adults
with an anxiety disorder find it difficult to manage their day-to-day lives and
are at an increased risk of comorbid depression, falls, physical and functional
disability, and loneliness. OBJECTIVE: To evaluate the effectiveness of
pharmacological, psychological and alternative therapies in older adults with an
anxiety disorder who have not responded, or have responded inadequately, to
treatment. DATA SOURCES: Electronic databases (MEDLINE, MEDLINE In-Process and
Other Non-Indexed citations, EMBASE, The Cochrane Library databases, PsycINFO and
Web of Science) were searched from inception to September 2013. Bibliographies of
relevant systematic reviews were hand-searched to identify additional potentially
relevant studies. ClinicalTrials.gov was searched for ongoing and planned
studies. REVIEW METHODS: A systematic review of the clinical effectiveness of
treatments for treatment-resistant anxiety in older adults was carried out.
RESULTS: No randomised controlled trial or prospective comparative observational
study was identified meeting the prespecified inclusion criteria. Therefore, it
was not possible to draw any conclusions on clinical effectiveness. LIMITATIONS:
As no study was identified in older adults, there is uncertainty as to which
treatments are clinically effective for older adults with an anxiety disorder who
have not responded to prior treatment. The comprehensive methods implemented to
carry out this review are a key strength of the research presented. However, this
review highlights the extreme lack of research in this area, identifying no
comparative studies, which is a marked limitation. CONCLUSIONS: Specific studies
evaluating interventions in older adults with an anxiety disorder who have not
responded to first-line treatment are needed to address the lack of evidence. The
lack of evidence in this area means that older adults are perhaps receiving
inappropriate treatment or are not receiving a particular treatment because there
is limited evidence to support its use. At this time there is scope to develop
guidance on service provision and, as a consequence, to advance the standard of
care received by older adults with a treatment-resistant anxiety disorder in
primary and secondary care. Evaluation of the relative clinical effectiveness and
acceptability of pharmacological and psychological treatment in older adults with
an anxiety disorder that has not responded to first-line treatment is key future
research to inform decision-making of clinicians and patients. An important
consideration would be the enrolment of older adults who would be representative
of older adults in general, i.e. those with multiple comorbid physical and mental
disorders who might require polypharmacy. STUDY REGISTRATION: The protocol for
the systematic review is registered on PROSPERO (registration number
CRD42013005612). FUNDING: The National Institute for Health Research Health
Technology Assessment programme.
PMID- 25110831
TI - Progression of DNA damage induced by a glyphosate-based herbicide in fish
(Anguilla anguilla) upon exposure and post-exposure periods--insights into the
mechanisms of genotoxicity and DNA repair.
AB - Roundup(r) is a glyphosate-based herbicide widely used with both agricultural and
non-agricultural purposes, which has been demonstrated to represent a risk to non
target aquatic organisms, namely fish. Among the described effects to fish,
genotoxicity has been pointed out as one of the most hazardous. However, the
genotoxic mechanisms of Roundup(r) as well as the involvement of the oxidative
DNA damage repair system are not entirely understood. Hence, this work aimed to
improve the knowledge on the progression of DNA damage upon short-term exposure
(3 days) and post-exposure (1-14 days) periods in association with DNA repair
processes in Anguilla anguilla exposed to Roundup(r) (58 and 116 MUg L-1). DNA
damage in hepatic cells was evaluated by the comet assay improved with the DNA
lesion specific endonucleases FPG and EndoIII. In order to evaluate the oxidative
DNA damage repair ability, an in vitro base excision repair (BER) assay was
performed, testing hepatic subcellular extracts. Besides the confirmation of the
genotoxic potential of this herbicide, oxidative damage was implicit as an
important mechanism of genetic damage, which showed to be transient, since DNA
integrity returned to the control levels on the first day after cessation of
exposure. An increased capacity to repair oxidative DNA damage emerging in the
post-exposure period revealed to be a crucial pathway for the A. anguilla
recovery; nevertheless, DNA repair machinery showed to be susceptible to
inhibitory actions during the exposure period, disclosing another facet of the
risk associated with the tested agrochemical.
PMID- 25110832
TI - Liquid/Liquid interfacial fabrication of thermosensitive and catalytically active
Ag nanoparticle-doped block copolymer composite foam films.
AB - An aqueous solution of AgNO3 (upper phase) and a DMF/CHCl3 solution of
polystyrene-b-poly(acryl acid)-b-polystyrene (PS-b-PAA-b-PS) or PS-b-PAA-b-PS/1,6
diaminohexane (DAH) (lower phase) constituted a planar liquid/liquid interface.
The lower phase gradually transformed to a water-in-oil (W/O) emulsion via
spontaneous emulsification due to the "ouzo effect". Polymer molecules, DAH
molecules, and Ag(+) ions assembled into microcapsules around emulsion droplets
that adsorbed at the planar liquid/liquid interface, resulting in formation of a
foam film. DAH acted as a cross-linker during this process. Transmission electron
microscopic observations indicated that Ag nanoclusters that were generated
through reduction of Ag(+) ions by DMF were homogeneously dispersed in the walls
of the foam structure. X-ray photoelectron spectroscopic investigations revealed
that Ag(I) and Ag(0) coexisted in the film, and Ag(I) transformed to Ag(0) after
further treatment. The film formed without DAH was not stable, while the film
formed with DAH was very stable due to intermolecular attraction between PAA and
DAH and formation of amides, as revealed by FTIR spectra. The film formed with
DAH exhibited high and durable catalytic activity for hydrogenation of nitro
compounds and, very interestingly, exhibited thermoresponsive catalytic behavior.
PMID- 25110834
TI - Successful embolization of iatrogenic ruptured coronary artery using Onyx: a new
technique.
AB - Iatrogenic perforation of coronary artery is rare during percutaneous coronary
intervention (PCI); however the complications are life-threatening. Patients in
this clinical setting may be treated either by stent placement, closure of the
perforation with fibrin glue or coils, or with emergency bypass surgery. Onyx, a
new material that has been used successfully in cerebral arteries, represents a
new and safe alternative. The advantage of Onyx is that it is easily injected
through a microcatheter and it allows for a longer injection time having also the
ability to reach difficult anatomical locations. We present the first case of
successful embolization of a right coronary artery perforation during coronary
angiography using Onyx.
PMID- 25110833
TI - Molecular speciation and dynamics of oxidized triacylglycerols in lipid droplets:
Mass spectrometry and coarse-grained simulations.
AB - Lipid droplets (LDs) are ubiquitous and physiologically active organelles
regulating storage and mobilization of lipids in response to metabolic demands.
Among the constituent LD neutral lipids, such as triacylglycerols, cholesterol
esters, and free fatty acids, oxidizable polyunsaturated molecular species may be
quite abundant, yet the structural and functional roles of their oxidation
products have not been studied. Our previous work documented the presence of
these peroxidized species in LDs. Assuming that hydrophilic oxygen-containing
functionalities may markedly change the hydrophobic/hydrophilic molecular
balance, here we utilized computational modeling to test the hypothesis that
lipid peroxidation causes redistribution of lipids between the highly hydrophobic
core and the polar surface (phospho)lipid monolayer-the area enriched with
integrated enzymatic machinery. Using quantitative liquid chromatography/mass
spectrometry, we characterized molecular speciation of oxTAGs in LDs of dendritic
cells in cancer and hypoxic trophoblasts cells as two cellular models associated
with dyslipidemia. Among the many types of oxidized lipids identified, we found
that oxidatively truncated forms and hydroxyl derivatives of TAGs were the
prevailing oxidized lipid species in LDs in both cell types. Using coarse-grained
molecular dynamics (CG-MD) simulations we established that lipid oxidation
changed their partitioning whereby oxidized lipids migrated into the outer
monolayer of the LD, where they can affect essential metabolic pathways and
undergo conversions, possibly leading to the formation of oxygenated lipid
mediators.
PMID- 25110835
TI - Expression quantitative trait loci in long non-coding RNA ZNRD1-AS1 influence
both HBV infection and hepatocellular carcinoma development.
AB - Zinc ribbon domain containing 1 (ZNRD1), cloned from human leukocyte antigen
(HLA) region, may play integral roles in diverse processes including immune
response against HBV infection and hepatocarcinogenesis. ZNRD1-AS1 (ZNRD1
antisense RNA 1) may be an important regulator of ZNRD1. By bioinformatics
analyses, we identified that several single nucleotide polymorphisms (SNPs) in
ZNRD1-AS1 may be expression quantitative trait loci (eQTLs) for ZNRD1. In this
study, we hypothesized that these eQTLs SNPs in ZNRD1-AS1 may influence both
chronic HBV infection and hepatocellular carcinoma (HCC) development. We designed
a case-control study of 1300 HBV-positive HCC patients, 1344 HBV persistent
carriers and, 1344 HBV natural clearance subjects to test the associations of
three ZNRD1 eQTLs SNPs (rs3757328, rs6940552 and, rs9261204) in ZNRD1-AS1 with
the risk of both chronic HBV infection and HCC. Logistic regression analyses in
additive genetic model showed that variant alleles of all the three SNPs
increased host HCC risk, whereas variant allele of rs3757328 was associated with
HBV clearance. Moreover, the haplotype containing variant alleles of the three
SNPs was significantly associated with both HCC development (adjusted OR = 1.18,
95% CI = 1.01-1.38, P = 0.035) and HBV clearance (adjusted OR = 0.83, 95% CI =
0.71-0.96, P = 0.013), when compared with the most frequent haplotype. In vitro
experiments showed that ZNRD1 knockdown inhibited the expression of HBV mRNA and
promoted proliferation of HepG2.2.15 cells. These findings suggest that ZNRD1
regulatory SNPs may be susceptibility makers for risk of both chronic HBV
infection and HCC.
PMID- 25110836
TI - Alcohol abuse and ERP components in Go/No-go tasks using alcohol-related stimuli:
impact of alcohol avoidance.
AB - Alcohol addictive behaviors are associated with a combination of deficits in
executive functions, such as a weak response inhibition, and potent automatic
appetitive responses to alcohol-related cues. The aim of the present study was to
investigate behavioral responses and event-related potentials (ERPs) associated
with specific response inhibition for alcohol-related cues. Thirty participants
(15 heavy drinkers and 15 light drinkers) took part in the study. Response
inhibition was assessed by a classical letter Go/No-go task and by a modified
alcohol Go/No-go task. Participants were also classified as high and low alcohol
avoiders. Results showed that heavy drinkers made more false alarms in the letter
Go/No-go task. In the alcohol Go/No-go task, an absence of N200 amplitude
anteriorization was found in heavy drinkers as compared to light drinkers.
Participants with a high level of alcohol avoidance exhibited more false alarms,
and higher N200 amplitude for the No-go trials as compared to the Go trials for
alcohol-related cues. Higher P300 amplitude was observed in low alcohol avoiders
for No-go as compared to Go trials. Therefore, a context involving alcohol
related cues disturbed inhibition capacities of high alcohol avoiders. These
results suggest that the level of alcohol avoidance must be taken into account in
studies investigating alcohol-related cognitive biases.
PMID- 25110838
TI - Gender-age interaction in incidence rates of childhood emotional disorders.
AB - BACKGROUND: The post-pubertal association of female gender with emotional
disorder is a robust finding. However, studies exploring the association of
gender and emotional disorders before puberty are few and present diverging
results. The aim of this study was to present gender-specific incidence rates of
emotional disorders throughout childhood. METHOD: This is a population-based
cohort study of 907,806 Danish 3- to 18-year-olds. The outcome was assignment of
an emotional disorder diagnosis based on in-patient and out-patient data from The
Danish Psychiatric Central Register. Outcome measures were incidence rates and
cumulative incidences for unipolar depressive disorder (ICD-10: F32-F33), anxiety
disorders (ICD-10: F40-F42), and emotional disorders with onset specific to
childhood (ICD-10: F93). RESULTS: Pre-pubertal incidence rates for depressive and
anxiety disorders were higher for boys than girls. At age 12 years the pattern
reversed. The cumulative incidence for any emotional disorder (F32-F33, F40-F42,
F93) on the 11th birthday was 0.52% (95% CI 0.50-0.55) for boys and 0.31% (95% CI
0.29-0.33) for girls. On the 19th birthday cumulative incidence was 2.33% (95% CI
2.24-2.43) for boys and 3.77% (95% CI 3.64-3.90) for girls. The pre-pubertal male
preponderance was also significant for depressive disorders (F32-F33, p =
0.00144) and anxiety disorders (F40-F42, F93, p < 0.00001) separately.
CONCLUSIONS: Emotional disorders seem to display a male preponderance before the
age of 12 years and a female preponderance thereafter. Studies exploring this
gender-age interaction are needed. Still, the results question the general
assumption that females throughout the lifespan are more at risk for emotional
disorders than males.
PMID- 25110839
TI - Treatment type and demographic characteristics as predictors for cancer
adjustment: Prospective trajectories of depressive symptoms in a population
sample.
AB - OBJECTIVE: Prospectively identifying individuals at heightened risk for
depression can alleviate the disease burden of distal physical and mental health
consequences after cancer onset. Our objective was to identify heterogeneous
trajectories of adjustment in cancer patients, using treatment-type as a
predictor. METHODS: Participants were followed for 6 years within the Health and
Retirement Study (HRS), a prospective population-based cohort study. The sample
consisted of 1,294 middle-aged participants who were assessed once before and 3
time points after their report of an initial cancer diagnosis. In addition to
self-reported depressive symptoms, subjects indicated receipt of surgical,
radiological, or chemical interventions as part of their usual oncological care.
RESULTS: Four symptom trajectories were identified with Latent Growth Mixture
Modeling: an increasing depression (10.5%), chronic depression (8.0%), depressed
improved (7.8%), and stable-low depression (73.7%). A conditional model using
participants with available predictor data (n = 545) showed individuals in the
emerging depression class were significantly more likely to have received
chemo/medication therapy when compared with the remitting depression, stable-low,
and chronic depression classes. Participants in the chronic and depressed
improved classes generally had worse baseline health, and the depressed-improved
were also younger in age. CONCLUSION: Patients who exhibited increasing
depressive symptoms had a greater probability of receiving chemo/medication
therapy than any other adjustment trajectory group, although the majority of
chemotherapy patients did not exhibit depressive symptom changes. These data
underscore the diversity of ways that patients adjust to cancer, and suggest
cancer treatment, baseline health, and age may influence long-term patterns of
psychological adjustment.
PMID- 25110842
TI - A cross-sectional analysis of the association between perceived network social
control and telomere length.
AB - OBJECTIVE: Social control in the health domain refers to attempts by social
network members to get an individual to modify their health behaviors. According
to the dual effects model of social control, having one's health behavior
controlled by others should be related to healthier behavioral change, but might
arouse psychological distress as one may resent being controlled. Despite
potential healthy behavior change, the stress of social control may thus be
detrimental as interpersonal stress has been related to negative health outcomes.
In the present study, the association between perceived social control and
telomere length was tested to examine its association to biological outcomes.
METHOD: In this cross-sectional study, a relatively healthy community sample of
140 middle age and older adults completed measures of perceived social control,
perceived stress, and health behaviors. Peripheral blood mononuclear cells were
used to determine telomere length. RESULTS: Main results showed that higher
levels of perceived direct social network control were associated with shorter
telomere length. These links were not influenced by statistical controls for
medication use, self-rated health, trait hostility, and optimism. Perceived
social control was also related to greater perceived stress but not health
behaviors overall. However, neither perceived stress nor health behaviors
mediated the link between social control and telomere length. CONCLUSIONS:
Although the study design precludes strong inferences, these results suggest that
perceived social control may be associated with cellular aging. These data also
highlight the utility of integrating biological outcomes into social control
models. (PsycINFO Database Record
PMID- 25110840
TI - Distress and type 2 diabetes-treatment adherence: A mediating role for perceived
control.
AB - OBJECTIVE: To better understand independent pathways linking emotional distress,
medication adherence, and glycemic control in adults with Type 2 diabetes, as
well as the potential mediating effects of perceived control over illness and
self-efficacy. METHOD: Adults with Type 2 diabetes (N = 142) were recruited for
an intervention study evaluating cognitive-behavioral therapy for adherence and
depression. Depressive symptom severity was assessed via semistructured
interview. Validated self-reports assessed diabetes-related distress, perceived
control over diabetes (perceived control), self-efficacy for diabetes self
management, and medication adherence. Glycemic control was evaluated by
hemoglobin A1C. Only baseline data were included in correlational and linear
regression analyses. RESULTS: Perceived control was an important mediator of
emotional distress for both medication adherence and A1C outcomes. Specifically,
regression analyses demonstrated that diabetes distress, but not depression
severity, was significantly related to medication adherence and A1C. Self
efficacy and perceived control were also independently associated with medication
adherence and A1C. Mediation analyses demonstrated a significant indirect effect
for diabetes distress and medication adherence through perceived control and self
efficacy. The relationship between distress and A1C was accounted for by an
indirect effect through perceived control. CONCLUSION: Results demonstrated that
diabetes-related emotional distress is associated with poorer treatment adherence
and glycemic control among adults with Type 2 diabetes; these relationships were
partially mediated through perceived control over diabetes. Perceptions of one's
personal ability to influence the course of diabetes may be important in
understanding the pathway between emotional distress and poor diabetes-treatment
outcomes.
PMID- 25110841
TI - HIV/STI risk-reduction intervention efficacy with South African adolescents over
54 months.
AB - OBJECTIVE: Little research has tested HIV/sexually transmitted infection (STI)
risk-reduction interventions' effects on early adolescents as they age into
middle and late adolescence. This study tested whether intervention-induced
reductions in unprotected intercourse during a 12-month period endured over a 54
month period and whether the intervention reduced the prevalence of STIs, which
increase risk for HIV. METHOD: Grade 6 learners (mean age = 12.4 years)
participated in a 12-month trial in Eastern Cape Province, South Africa, in which
9 matched pairs of schools were randomly selected and within pairs randomized to
a theory-based HIV/STI risk-reduction intervention or an attention-control
intervention. They completed 42- and 54-month postintervention measures of
unprotected intercourse (the primary outcome), other sexual behaviors,
theoretical constructs, and, at 42- and 54-month follow-up only, biologically
confirmed curable STIs (chlamydial infection, gonorrhea, and trichomoniasis) and
herpes simplex virus 2. RESULTS: The HIV/STI risk-reduction intervention reduced
unprotected intercourse averaged over the entire follow-up period (OR = 0.42, 95%
CI [0.22, 0.84]), an effect not significantly reduced at 42- and 54-month follow
up compared with 3-, 6-, and 12-month follow-ups. The intervention caused
positive changes on theoretical constructs averaged over the 5 follow-ups,
although most effects weakened at long-term follow-up. Although the
intervention's main effect on STIs was nonsignificant, an Intervention Condition
* Time interaction revealed that it significantly reduced curable STIs at 42
month follow-up in adolescents who reported sexual experience. CONCLUSION: These
results suggest that theory-based behavioral interventions with early adolescents
can have long-lived effects in the context of a generalized severe HIV epidemic.
PMID- 25110843
TI - Anger arousal and behavioral anger regulation in everyday life among patients
with chronic low back pain: Relationships to patient pain and function.
AB - OBJECTIVE: The objective of this study was to determine the degree to which
patient anger arousal and behavioral anger regulation (expression, inhibition)
occurring in the course of daily life was related to patient pain and function as
rated by patients and their spouses. METHOD: Married couples (N = 105) (one
spouse with chronic low back pain) completed electronic daily diaries, with
assessments 5 times/day for 14 days. Patients completed items on their own state
anger, behavioral anger expression and inhibition, and pain-related factors.
Spouses completed items on their observations of patient pain-related factors.
Hierarchical linear modeling was used to test concurrent and lagged
relationships. RESULTS: Patient-reported increases in state anger were related to
their reports of concurrent increases in pain and pain interference and to spouse
reports of patient pain and pain behavior. Patient-reported increases in
behavioral anger expression were related to lagged increases in pain intensity
and interference and decreases in function. Most of these relationships remained
significant with state anger controlled. Patient-reported increases in behavioral
anger inhibition were related to concurrent increases in pain interference and
decreases in function, which also remained significant with state anger
controlled. Patient-reported increases in state anger were related to lagged
increases in spouse reports of patient pain intensity and pain behaviors.
CONCLUSIONS: Results indicate that in patients with chronic pain, anger arousal
and behavioral anger expression and inhibition in everyday life are related to
elevated pain intensity and decreased function as reported by patients. Spouse
ratings show some degree of concordance with patient reports.
PMID- 25110844
TI - Peers promoting physical activity among breast cancer survivors: A randomized
controlled trial.
AB - OBJECTIVE: Although studies have shown that physical activity (PA) can reduce
some treatment-related side effects of breast cancer, there is a need to offer PA
programs outside of research settings to reach more cancer survivors. We
partnered with the American Cancer Society's Reach to Recovery (RTR) program to
train their volunteers (breast cancer survivors) to deliver a 12-week PA
intervention to other breast cancer survivors. METHOD: We conducted a randomized
controlled trial to compare the PA intervention delivered by RTR volunteers (PA
plus RTR) with contact control (RTR control). Eighteen RTR volunteers/coaches
(Mage = 54.9 years; Mtime since diagnosis = 7.0 years) delivered the contact
control condition or the PA intervention. Seventy-six breast cancer survivors in
New England (Mage = 55.6 years; Mtime since diagnosis = 1.1 years) were
randomized to 1 of the 2 groups. At baseline, 12 weeks (postintervention), and at
24 weeks, participants wore an accelerometer for 7 days, were interviewed about
their PA, and reported their motivational readiness for PA. RESULTS: Adjusted,
mixed-effects longitudinal regression models showed significant group differences
favoring the PA plus RTR group in minutes of moderate to vigorous PA at 12 weeks
(Mdifference = 103 min/week, p < .001) and at 24 weeks (Mdifference = 34.7
min/week, p = .03). Results were corroborated with significant group differences
in accelerometer data favoring the PA plus RTR group at both time points.
CONCLUSION: Peer volunteers were able to significantly increase PA among cancer
survivors relative to contact control. Partnerships with existing volunteer
programs can help to widen the reach of behavioral interventions among cancer
survivors. (PsycINFO Database Record
PMID- 25110845
TI - Hostility and the risk of peptic ulcer in the GAZEL cohort.
AB - OBJECTIVE: Evidence for an association between hostility and peptic ulcer mainly
relies on cross-sectional studies. Prospective studies are rare and have not used
a validated measure of hostility. This prospective study aimed to examine the
association between hostility and peptic ulcer in the large-scale French GAZEL
cohort. METHOD: In 1993, 14,674 participants completed the Buss and Durkee
Hostility Inventory. Participants were annually followed-up from 1994 to 2011.
Diagnosis of peptic ulcer was self-reported. The association between hostility
scores and ulcer incidence was measured by hazard ratios (HR) and 95% confidence
intervals computed through Cox regression. RESULTS: Among 13,539 participants
free of peptic ulcer history at baseline, 816 reported a peptic ulcer during a
mean follow-up of 16.8 years. Adjusting for potential confounders, including
smoking, occupational grade, and a proxy for nonsteroidal anti-inflammatory drug
exposure, ulcer incidence was positively associated with total hostility (HR per
SD: 1.23, confidence interval: 1.14-1.31), behavioral hostility (HR per SD: 1.13,
confidence interval: 1.05-1.21), cognitive hostility (HR per SD: 1.26, confidence
interval: 1.18-1.35), and irritability (HR per SD: 1.20, confidence interval:
1.12-1.29). The risk of peptic ulcer increased from the lowest to the highest
quartile for all hostility measures (p for linear trend < .05). CONCLUSIONS:
Hostility might be associated with an increased risk of peptic ulcer. Should
these results be replicated, further studies would be needed to explore the
underlying mechanisms.
PMID- 25110846
TI - Racial and sexual minority women's receipt of medical assistance to become
pregnant.
AB - OBJECTIVE: This study aimed to determine rates at which racial minority (i.e.,
non-White) and sexual minority (i.e., lesbian and bisexual-identified) women in
the United States receive medical help to become pregnant. Income and insurance
coverage discrepancies were hypothesized to mediate differences in receipt of
medical help as a function of race and sexual orientation. METHOD: Two studies
compared rates at which adult women ages 21-44 reported receiving medical help to
become pregnant as a function of race and sexual orientation, using data from 2
cycles of the National Survey of Family Growth (the 2002 wave in Study 1, and the
2006-2010 wave in Study 2). Mediation analyses controlling for age and education
level evaluated whether race and sexual orientation were positively associated
with receipt of medical pregnancy help, as mediated by insurance coverage and
income. RESULTS: Heterosexual White women reported receiving medical fertility
assistance at nearly double the rates of women who identified as non-White,
sexual minority, or both. Differences in rates of help received by White and non
White groups were only partially mediated by insurance coverage and income in
both studies. Insurance and income discrepancies accounted for all differences
between sexual minority and heterosexual women's receipt of pregnancy help in
Study 1; insurance coverage alone explained differences in Study 2. CONCLUSIONS:
Researchers often indicate that economic differences are responsible for health
disparities between minority and majority groups, but this may not be the case
for all women pursuing medical fertility assistance. Possible origins of these
disparities are discussed.
PMID- 25110847
TI - Medication beliefs mediate between depressive symptoms and medication adherence
in cystic fibrosis.
AB - OBJECTIVE: Depression is a known barrier to regimen adherence for chronic
conditions. Despite elevated depression rates and complex regimens for people
with cystic fibrosis (CF), little is known about associations between depressive
symptoms and CF adherence. One possibility is that depressive symptoms distort
beliefs about medications, which may influence adherence. METHOD: Adolescents and
adults (N = 128; mean age = 29 +/- 11 years, range = 16-63, 93% Caucasian) with
CF reported on depressive symptoms and medication beliefs (self-efficacy,
motivation, perceived importance, and outcome expectancies related to taking
medications). Medication adherence was assessed objectively through pharmacy
refill data. Cross-sectional structural equation models evaluated medication
beliefs as a mediator between depressive symptoms and medication adherence.
RESULTS: Twenty-three percent of participants exceeded clinical cutoffs for
depressive symptoms. Participants took less than half of prescribed pulmonary
medications (mean adherence rate = 44.4 +/- 26.7%). Depressive symptoms were
correlated with adherence (r = -.22, p < .05), and medication beliefs (b = -0.13,
95% CI [-0.24, -0.03]) significantly mediated this relation. Higher depressive
symptoms were associated with less positive medication beliefs (b = -0.27, p <
.01), which were associated with lower medication adherence (b = 0.49, p < .01).
CONCLUSIONS: Depressive symptoms are related to beliefs about and adherence to CF
medications. Monitoring depressive symptoms and medication beliefs in routine CF
care may help identify risks for nonadherence and facilitate interventions to
reduce depression, adaptive medication beliefs, and ultimately improve adherence
and CF management. (PsycINFO Database Record
PMID- 25110848
TI - Prepregnancy body mass index, gestational weight gain, and elevated depressive
symptoms in a Hispanic cohort.
AB - OBJECTIVES: Our objective was to assess the associations among prepregnancy Body
Mass Index (BMI), gestational weight gain (GWG), and elevated depressive symptoms
across pregnancy. METHODS: We evaluated these associations among 1,090
participants in Proyecto Buena Salud, a prospective cohort study of Hispanic
(predominantly Puerto Rican) women in Western Massachusetts. BMI and GWG were
self-reported; GWG was classified according to the 2009 Institute of Medicine
guidelines. Depressive symptoms were assessed in early, mid-, and late pregnancy
using the 10-item Edinburgh Postnatal Depression Scale (EPDS). We defined
elevated depressive symptoms as EPDS scores >=13 and >=15. RESULTS: In
multivariable, longitudinal modeling, overweight (25.0 to <30 kg/m2) women had an
odds ratio of 0.53 (95% CI [0.31, 0.90]) for EPDS scores >=13 and 0.51 (95% CI
[0.28, 0.91]) for EPDS scores >=15 compared to normal weight women. We did not
observe an association between GWG or an interaction between BMI and GWG, in
predicting elevated depressive symptoms. CONCLUSIONS: Our findings provide
preliminary support for an association of prepregnancy overweight status and
lower depressive symptoms across pregnancy in Hispanic women. Future research
should focus on potential social and cultural differences in perceptions of
weight and weight gain in the perinatal period and how these influence
psychological health.
PMID- 25110849
TI - Capability to care: supporting the health of informal caregivers for older
people.
AB - OBJECTIVE: The study investigated the capabilities important to the health of
people caring informally for elders. METHOD: Over 4 months, 60 informal
caregivers from New Zealand participated in online discussion boards that
provided a set of virtual forums. It drew upon the Capability Approach (Sen,
1980) to frame a qualitative inquiry whereby participants could anonymously
respond to an evolving joint discussion of their health needs. Template analysis
based on Nussbaum's (2007) list of essential human capabilities informed the
thematic analysis. RESULTS: The results showed the interconnected nature of
capabilities and the importance of emotions in informal caregiving. Emotional
attachment influenced the caregivers' freedom to choose how they lived their
lives. Because they valued the capability to care for loved ones, the caregivers
traded other capabilities, putting their lives on hold, and compromising their
wellbeing. CONCLUSION: The self-abnegation reported by the caregivers highlighted
the relational nature of caregiving and challenged a dominant perspective in the
caregiving literature that focuses on the burdens of caregiving. The significance
of emotional aspects related to the valued capabilities of caregiving suggests
the need to acknowledge caregiving as an interdependent relationship and emotions
as a crucial place to focus future support for caregivers.
PMID- 25110850
TI - Examining the moderating effect of depressive symptoms on the relation between
exercise and self-efficacy during the initiation of regular exercise.
AB - OBJECTIVE: People with depressive symptoms report lower levels of exercise self
efficacy and are more likely to discontinue regular exercise than others, but it
is unclear how depressive symptoms affect the relation between exercise and self
efficacy. We sought to clarify whether depressive symptoms moderate the relations
between exercise and same-day self-efficacy, and between self-efficacy and next
day exercise. METHODS: Participants (n = 116) were physically inactive adults
(35% reported clinically significant depressive symptoms) who initiated regular
exercise and completed daily assessments for 4 weeks. Mixed linear models were
used to test whether (a) self-efficacy differed on days when exercise did and did
not occur, (b) self-efficacy predicted next-day exercise, and (c) these relations
were moderated by depressive symptoms. RESULTS: First, self-efficacy was lower on
days when no exercise occurred, but this difference was larger for people with
high depressive symptoms (p < .001). They had lower self-efficacy than people
with low depressive symptoms on days when no exercise occurred (p = .03), but
self-efficacy did not differ on days when exercise occurred (p = .34). Second,
self-efficacy predicted greater odds of next-day exercise, OR = 1.12, 95% [1.04,
1.21], but depressive symptoms did not moderate this relation, OR = 1.00, 95% CI
[.99, 1.01]. CONCLUSIONS: During exercise initiation, daily self-efficacy is more
strongly related to exercise occurrence for people with high depressive symptoms
than those with low depressive symptoms, but self-efficacy predicts next-day
exercise regardless of depressive symptoms. The findings specify how depressive
symptoms affect the relations between exercise and self-efficacy and underscore
the importance of targeting self-efficacy in exercise interventions, particularly
among people with depressive symptoms. (PsycINFO Database Record
PMID- 25110851
TI - Posttraumatic stress disorder and responses to couple conflict: implications for
cardiovascular risk.
AB - OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with increased risk
of coronary heart disease (CHD) and difficulties in intimate relationships.
Greater frequency and severity of couple conflict and greater cardiovascular
reactivity to such conflict might contribute to CHD risk in those with PTSD, but
affective and physiological responses to couple conflict have not been examined
previously in this population. METHOD: In a preliminary test of this hypothesis,
32 male veterans of the Iraq and Afghanistan Wars with PTSD and their female
partners, and 33 control male veterans without PTSD and their female partners
completed relationship quality assessments and a conflict discussion task. PTSD
diagnosis was confirmed through diagnostic interviews and questionnaires. State
anger, state anxiety, and cardiovascular measures (i.e., blood pressure, heart
rate) were recorded during baseline and the conflict discussion. RESULTS:
Compared with controls, PTSD couples reported greater couple conflict and less
warmth, and displayed pronounced increases in anger and greater increases in
systolic blood pressure in response to the conflict task (all ps < .05; range
eta2: .05-.24). Partners in the PTSD group exhibited similar, if not greater,
responses as veterans. CONCLUSIONS: This was the first investigation to document
emotional and cardiovascular responses to couple conflict in veterans with PTSD
and their partners. PTSD was associated with greater frequency and severity of
couple conflict, and greater anger and cardiovascular reactivity to conflict
discussions. Anger and physiological responses to couple discord might contribute
to CHD risk in veterans with PTSD, and perhaps their partners, as well.
PMID- 25110852
TI - Expression of executive control in situational context: Effects of facilitating
versus restraining cues on snack food consumption.
AB - OBJECTIVES: To examine the effects of executive function (EF) on objectively
measured high-calorie snack food consumption in 2 age groups and to explore the
moderating influence of environmental cues. METHODS: In Study 1, 43 older adults
(M(age) = 74.81) and in Study 2, 79 younger adults (M(age) = 18.71) completed
measures of EF and subsequently participated in a bogus taste-test paradigm
wherein they were required to rate 3 highly appetitive (but high-calorie) snack
foods on taste and texture. Grams of snack food consumed was measured covertly in
the presence randomly assigned contextual cues (explicit semantic cues in Study
1; implicit visual cues in Study 2) that were facilitating or restraining in
nature. RESULTS: Findings indicated that in both age groups, stronger EF
predicted lower consumption of snack foods across conditions, and the effects of
EF were most pronounced in the presence of facilitating cues. CONCLUSIONS: Older
and younger adults with weaker EF tend to consume more high-calorie snack food
compared with their stronger EF counterparts. These tendencies appear to be
especially amplified in the presence of facilitating cues.
PMID- 25110853
TI - Caregivers' burden and depressive symptoms: the moderational role of attachment
orientations.
AB - OBJECTIVE: The current study explored whether attachment orientations moderate
the associations between caregiver burden and depressive symptoms among women
coping with their partners' first time acute coronary syndrome. The association
between burden and depression was hypothesized to be stronger among caregivers
high on anxious attachment than among caregivers low on this dimension. In
addition, the association between burden and depressive symptoms was hypothesized
to be weaker among caregivers higher on avoidant attachment than among those
lower on this dimension. METHOD: The sample consisted of 111 female caregivers of
male patients admitted to the cardiac care unit of a hospital in Israel.
Caregivers completed a measure of attachment orientations during patients'
hospitalization (baseline). Caregiver burden was measured 1 month later.
Depressive symptoms were measured at baseline and again at 6-month follow-up.
Structural equation modeling was used to test the moderational models. RESULTS:
The association between caregiver burden and depressive symptoms at follow-up was
moderated by attachment-related anxiety but not attachment-related avoidance.
Congruent with predictions, a stronger association between caregiver burden and
depressive symptoms occurred for caregivers with greater (vs. lower) attachment
anxiety. CONCLUSIONS: The findings shed light on the possible dynamics among
attachment orientations and affect regulation when coping with one's partner's
illness. The findings are discussed in light of Pietromonaco, Uchino, and Dunkel
Schetter's (2013) model of integrating attachment into health psychology
research.
PMID- 25110854
TI - Modeling the association between lifecourse socioeconomic disadvantage and
systemic inflammation in healthy adults: The role of self-control.
AB - OBJECTIVE: We sought to identify pathways connecting lifecourse socioeconomic
status (SES) with chronic, low-grade inflammation, focusing on the explanatory
roles of self-control, abdominal adiposity, and health practices. METHODS:
Participants were 360 adults aged 15-55 who were free of chronic medical
conditions. They were roughly equally divided between low and high current SES,
with each group further divided between low and high early-life SES. Structural
equation modeling (SEM) was used to identify direct and indirect pathways linking
early-life and current SES with low-grade, chronic inflammation in adulthood, as
manifest by serum interleukin-6 and C-reactive protein. Low SES was hypothesized
to relate to inflammation by reducing self-control, which in turn was
hypothesized to facilitate lifestyle factors that potentiate inflammation
(smoking, alcohol use, sedentary behavior, and weight gain). RESULTS: Analyses
revealed that self-control was pivotal in linking both early-life and current SES
to inflammation. Low early-life SES was related to a harsher family climate, and
in turn lower adult self-control, over and above the effects of current SES.
Controlling for early-life SES, low current SES was associated with perceived
stress and, in turn, diminished self-control. Results showed that lower self
control primarily operated through higher abdominal adiposity to associate with
greater inflammation. CONCLUSIONS: The findings suggest a mechanistic scenario
wherein low SES in early life or adulthood depletes self-control and, in turn,
fosters adiposity and inflammation. These pathways should be studied
longitudinally to elucidate and potentially ameliorate socioeconomic disparities
in health.
PMID- 25110855
TI - Ossification sequence and genetic patterning in the mouse axial skeleton.
AB - We provide novel data on vertebral ontogeny in the mouse, the mammalian model-of
choice for developmental studies. Most previous studies on ossification sequences
in mice have focused on pooled elements of the spine (cervicals, thoracics,
lumbars, sacrals, and caudals). Here, we contribute data on ossification
sequences in the neural arches and centra to provide a comparative basis upon
which to evaluate mammalian diversity of the axial skeleton. In attempt to
explain the ossification pattern observed, we compared our observations with the
phenotype of Cdx over-expresser mice. We use high-resolution X-ray
microtomography and clearing and staining techniques to quantify the precise
sequential ossification pattern of the mouse spine. We show that micro-CT scans
perform better in all cases whereas clearing and staining exhibit sensitivity to
the presence of semi-opaque tissue. We observe that the centra of wild-type mice
always ossify after neural arches and that the ossification of the neural arches
proceeds from two loci. The ossification of the centra appears more complex,
especially in the neck where ossification is delayed and does not just follow the
order of the vertebrae along the anterior-posterior axis. Our findings also
suggest that Cdx genes' expression levels may be involved in the delayed
ossification in the neck centra.
PMID- 25110857
TI - Pregnancy outcomes of HIV-positive women in a tertiary centre in the UK.
AB - With the advent of highly active antiretroviral therapy (HAART), the mother-to
child HIV transmission rate in the UK has reduced to less than 2%. A review of
delivery outcomes of 106 HIV-positive pregnant women in a tertiary centre between
January 2005 and December 2010 was conducted. A total of 20 women had detectable
plasma viral load at 36 weeks, or before in the two women who delivered preterm.
Various peripartum management measures were undertaken in women with detectable
viral load close to delivery, to accelerate reduction in plasma viral load and to
reduce the risk of HIV transmission to the fetus. In our review, the overall
mother-to-child transmission rate was less than 1% and in women with undetectable
viral load at 36 weeks, it was 0% (zero), which signifies the importance of
strict virological control and a multidisciplinary approach, which plays an
important role in the successful achievement of this.
PMID- 25110856
TI - Closure versus non-closure of the peritoneum at caesarean section: short- and
long-term outcomes.
AB - BACKGROUND: Caesarean section is a very common surgical procedure worldwide.
Suturing the peritoneal layers at caesarean section may or may not confer
benefit, hence the need to evaluate whether this step should be omitted or
routinely performed. OBJECTIVES: The objective of this review was to assess the
effects of non-closure as an alternative to closure of the peritoneum at
caesarean section on intraoperative and immediate- and long-term postoperative
outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth
Group's Trials Register (1 November 2013). SELECTION CRITERIA: Randomised
controlled trials comparing leaving the visceral or parietal peritoneum, or both,
unsutured at caesarean section with a technique which involves suturing the
peritoneum in women undergoing elective or emergency caesarean section. DATA
COLLECTION AND ANALYSIS: Two review authors independently assessed trials for
inclusion and risk of bias, extracted data and checked it for accuracy. MAIN
RESULTS: A total of 29 trials were included in this review and 21 trials (17,276
women) provided data that could be included in an analysis. The quality of the
trials was variable. 1. Non-closure of visceral and parietal peritoneum versus
closure of both parietal layersSixteen trials involving 15,480 women, were
included and analysed, when both parietal peritoneum was left unclosed versus
when both peritoneal surfaces were closed. Postoperative adhesion formation was
assessed in only four trials with 282 women, and no difference was found between
groups (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.76 to 1.29). There
was significant reduction in the operative time (mean difference (MD) -5.81
minutes, 95% CI -7.68 to -3.93). The duration of hospital stay in a total of 13
trials involving 14,906 women, was also reduced (MD -0.26, 95% CI -0.47 to -0.05)
days. In a trial involving 112 women, reduced chronic pelvic pain was found in
the peritoneal non-closure group. 2. Non-closure of visceral peritoneum only
versus closure of both peritoneal surfacesThree trials involving 889 women were
analysed. There was an increase in adhesion formation (two trials involving 157
women, RR 2.49, 95% CI 1.49 to 4.16) which was limited to one trial with high
risk of bias.There was reduction in operative time, postoperative days in
hospital and wound infection. There was no significant reduction in postoperative
pyrexia. 3. Non-closure of parietal peritoneum only versus closure of both
peritoneal layersThe two identified trials involved 573 women. Neither study
reported on postoperative adhesion formation. There was reduction in operative
time and postoperative pain with no difference in the incidence of postoperative
pyrexia, endometritis, postoperative duration of hospital stay and wound
infection. In only one study, postoperative day one wound pain assessed by the
numerical rating scale, (MD -1.60, 95% CI -1.97 to -1.23) and chronic abdominal
pain d by the visual analogue score (MD -1.10, 95% CI -1.39 to -0.81) was reduced
in the non-closure group. 4. Non-closure versus closure of visceral peritoneum
when parietal peritoneum is closed.There was reduction in all the major urinary
symptoms of frequency, urgency and stress incontinence when the visceral
peritoneum is left unsutured. AUTHORS' CONCLUSIONS: There was a reduction in
operative time across all the subgroups. There was also a reduction in the period
of hospitalisation post-caesarean section except in the subgroup where parietal
peritoneum only was not sutured where there was no difference in the period of
hospitalisation. The evidence on adhesion formation was limited and inconsistent.
There is currently insufficient evidence of benefit to justify the additional
time and use of suture material necessary for peritoneal closure. More robust
evidence on long-term pain, adhesion formation and infertility is needed.
PMID- 25110858
TI - Diffusion NMR of molecular cages and capsules.
AB - In the last decade diffusion NMR and diffusion ordered spectroscopy (DOSY) have
become important analytical tools for the characterization of supramolecular
systems in solution. Diffusion NMR can be used to glean information on the
(effective) size and shape of molecular species, as well as to probe inter
molecular interactions and can be used to estimate the association constant (Ka)
of a complex. In addition, the diffusion coefficient, as obtained from diffusion
NMR, is a much more intuitive parameter than the chemical shift for probing self
association, aggregation and inter-molecular interactions. The diffusion
coefficient may be an even more important analytical parameter in systems in
which the formed supramolecular entity has the same symmetry as its building
units, when there is a large change in the molecular weight, where many molecular
species are involved in the formation of the supramolecular systems, and when
proton transfer may occur which, in turn, may affect the chemical shift. Some of
the self-assembled molecular capsules and cages prepared in the last decade
represent such supramolecular systems and in the present review, following a
short introduction on diffusion NMR, we survey the contribution of diffusion NMR
and DOSY in the field of molecular containers and capsules. We will first focus
on the role played by diffusion NMR in the field of hydrogen bond driven self
assembled capsules. We then survey the contributions of diffusion NMR and DOSY to
the study and characterization of metal-ligand cages and capsules. Finally, we
describe a few recent applications of diffusion NMR in the field of hydrophobic,
electrostatic and covalent containers.
PMID- 25110859
TI - The role of doppler waveforms in the fetal main pulmonary artery in the
prediction of neonatal respiratory distress syndrome.
AB - OBJECTIVE: To describe changes in the Doppler waveforms of the fetal main
pulmonary artery (MPA) throughout gestation and to assess their predictive value
of neonatal respiratory distress syndrome (RDS). STUDY DESIGN: In the first phase
of this study, we performed Doppler measurement of MPA acceleration time (AT),
ejection time (ET), peak systolic velocity, end-diastolic velocity, mean
velocity, pulsatility index, and resistance index in 288 healthy fetuses. In the
second phase, we carried out these measurements in a prospective cohort of 52
pregnant women with impending preterm birth. RESULTS: In phase I, satisfactory
fetal MPA Doppler recordings were collected in 284 of 288 (98.6%) normal fetuses.
Significant and positive linear correlations were found between gestational age
and AT, AT/ET ratio, peak systolic velocity, and mean velocity (p < 0.01), with
the strongest correlations concerning AT (r = 0.898) and AT/ET ratio (r = 0.868).
In phase II, satisfactory fetal MPA Doppler waveforms were obtained in 43 of 44
(97.7%) fetuses. Of these, 14 (32.6%) developed RDS and 29 did not. Using less
than or equal to the fifth percentile as a gestational age-specific cutoff, AT
alone could predict RDS with a sensitivity of 78.6% and a specificity of 89.7%.
The AT/ET ratio could predict RDS with 71.4% sensitivity and 93.1% specificity.
CONCLUSIONS: Fetal MPA Doppler velocimetry can reliably be obtained throughout
gestation. AT and AT/ET ratios of the fetal MPA Doppler waveform may help
identifying fetuses at risk of developing neonatal RDS.
PMID- 25110860
TI - Large and fast single-crystal resistive humidity sensitivity of metal pnictide
halides containing van der Waals host-guest interactions.
AB - Two new metal pnictide halides, (Hg(9.75)As(5.5))(GaCl4)3 and (Hg13Sb8)(ZnBr4)4,
have been prepared by solid-state reactions. Their structures feature 3D cationic
host frameworks built of mercury pnictide polyhedra and form 1D tunnels filled
with discrete guest halide polyanions; the guests and hosts are assembled by van
der Waals interactions. Both complexes exhibit good single-crystal humidity
sensitivity, with a humidity sensitivity factor as big as three orders of
magnitude, a quick resistance response, fast recovery, and good reproducibility.
This study provide a new way to design promising resistive humidity detectors by
introducing van der Waals host-guest interactions into their structures.
PMID- 25110861
TI - Mid-level practitioners in dermatology: a need for further study and oversight.
PMID- 25110862
TI - Robust non-wetting PTFE surfaces by femtosecond laser machining.
AB - Nature shows many examples of surfaces with extraordinary wettability,which can
often be associated with particular air-trapping surface patterns. Here,robust
non-wetting surfaces have been created by femtosecond laser ablation of
polytetrafluoroethylene (PTFE). The laser-created surface structure resembles a
forest of entangled fibers, which support structural superhydrophobicity even
when the surface chemistry is changed by gold coating. SEM analysis showed that
the degree of entanglement of hairs and the depth of the forest pattern
correlates positively with accumulated laser fluence and can thus be influenced
by altering various laser process parameters. The resulting fibrous surfaces
exhibit a tremendous decrease in wettability compared to smooth PTFE surfaces;
droplets impacting the virgin or gold coated PTFE forest do not wet the surface
but bounce off. Exploratory bioadhesion experiments showed that the surfaces are
truly air-trapping and do not support cell adhesion. Therewith, the created
surfaces successfully mimic biological surfaces such as insect wings with robust
anti-wetting behavior and potential for antiadhesive applications. In addition,
the fabrication can be carried out in one process step, and our results clearly
show the insensitivity of the resulting non-wetting behavior to variations in the
process parameters,both of which make it a strong candidate for industrial
applications.
PMID- 25110863
TI - A sensitive and effective proteomic approach to identify she-donkey's and goat's
milk adulterations by MALDI-TOF MS fingerprinting.
AB - She-donkey's milk (DM) and goat's milk (GM) are commonly used in newborn and
infant feeding because they are less allergenic than other milk types. It is,
therefore, mandatory to avoid adulteration and contamination by other milk
allergens, developing fast and efficient analytical methods to assess the
authenticity of these precious nutrients. In this experimental work, a sensitive
and robust matrix-assisted laser desorption/ionization time-of-flight mass
spectrometry (MALDI-TOF MS) profiling was designed to assess the genuineness of
DM and GM milks. This workflow allows the identification of DM and GM
adulteration at levels of 0.5%, thus, representing a sensitive tool for milk
adulteration analysis, if compared with other laborious and time-consuming
analytical procedures.
PMID- 25110864
TI - Biosurfactant mediated biosynthesis of selected metallic nanoparticles.
AB - Developing a reliable experimental protocol for the synthesis of nanomaterials is
one of the challenging topics in current nanotechnology particularly in the
context of the recent drive to promote green technologies in their synthesis. The
increasing need to develop clean, nontoxic and environmentally safe production
processes for nanoparticles to reduce environmental impact, minimize waste and
increase energy efficiency has become essential in this field. Consequently,
recent studies on the use of microorganisms in the synthesis of selected
nanoparticles are gaining increased interest as they represent an exciting area
of research with considerable development potential. Microorganisms are known to
be capable of synthesizing inorganic molecules that are deposited either intra-
or extracellularly. This review presents a brief overview of current research on
the use of biosurfactants in the biosynthesis of selected metallic nanoparticles
and their potential importance.
PMID- 25110865
TI - BMP4 protects rat pulmonary arterial smooth muscle cells from apoptosis by
PI3K/AKT/Smad1/5/8 signaling.
AB - Bone morphogenetic protein-4 (BMP4), a member of the transforming growth factor
beta (TGF-beta) family of growth factors, is activated and increased under
hypoxic conditions, which plays an important role in the progression of pulmonary
arterial hypertension (PAH). Previous studies have shown that BMP4 is involved in
the regulation of proliferation, differentiation, migration and apoptosis of
various cell types. However, the precise mechanisms involved in the regulation of
pulmonary artery smooth muscle cells (PASMCs) in PAH are still incompletely
understood. It has been reported that AKT is a critical regulator of cell
survival and vascular remodeling. Therefore, there may be crosstalk between BMP4
anti-apoptotic processes and PI3K/AKT survival effect in rat PASMCs. To test this
hypothesis, we performed confocal, cell viability measurement, mitochondrial
potential, real-time polymerase chain reaction (PCR), and Western blot analysis
to determine the role of BMP4 on cell survival and apoptosis. We found that
hypoxia up-regulated the expression of BMP4. BMP4 promoted cell survival, reduced
mitochondrial depolarization, and increased the expression of Bcl-2 and
procaspase-3 in PASMCs under serum-deprived condition. These effects were
reversed by PI3K/AKT inhibitors (LY294002 and wortmannin). Thus, these findings
indicate that BMP4 protects PASMCs from apoptosis at least in part, mediated via
the PI3K/AKT pathway.
PMID- 25110866
TI - Lutein inhibits the migration of retinal pigment epithelial cells via cytosolic
and mitochondrial Akt pathways (lutein inhibits RPE cells migration).
AB - During the course of proliferative vitreoretinopathy (PVR), the retinal pigment
epithelium (RPE) cells will de-differentiate, proliferate, and migrate onto the
surfaces of the sensory retina. Several studies have shown that platelet-derived
growth factor (PDGF) can induce migration of RPE cells via an Akt-related
pathway. In this study, the effect of lutein on PDGF-BB-induced RPE cells
migration was examined using transwell migration assays and Western blot
analyses. We found that both phosphorylation of Akt and mitochondrial
translocation of Akt in RPE cells induced by PDGF-BB stimulation were suppressed
by lutein. Furthermore, the increased migration observed in RPE cells with
overexpressed mitochondrial Akt could also be suppressed by lutein. Our results
demonstrate that lutein can inhibit PDGF-BB induced RPE cells migration through
the inhibition of both cytoplasmic and mitochondrial Akt activation.
PMID- 25110868
TI - The inflammation-related gene S100A12 is positively regulated by C/EBPbeta and AP
1 in pigs.
AB - S100A12 is involved in the inflammatory response and is considered an important
marker for many inflammatory diseases in humans. Our previous studies indicated
that the S100A12 gene was abundant in the immune tissues of pigs and was
significantly upregulated during infection with Haemophilus parasuis (HPS) or
porcine circovirus type 2 (PCV2). In this study, the mechanism of transcriptional
regulation of S100A12 was investigated in pigs. Our results showed that S100A12,
CCAAT/enhancer-binding protein beta (C/EBPbeta) and activator protein-1 (AP-1)
genes were up-regulated in PK-15 (ATCC, CCL-33) cells when treated with LPS or
Poly I: C. Additionally, the promoter activity and expression level of the
S100A12 gene were significantly upregulated when C/EBPbeta or AP-1 were
overexpressed. We utilized electromobility shift assays (EMSA) to confirm that
C/EBPbeta and AP-1 could directly bind the S100A12 gene promoter. We also found
that the transcriptional activity and expression levels of C/EBPbeta and AP-1
could positively regulate each other. Furthermore, the promoter activity of the
S100A12 gene was higher when C/EBPbeta and AP-1 were cotransfected than when they
were transfected individually. We concluded that the S100A12 gene was
cooperatively and positively regulated by C/EBPbeta and AP-1 in pigs. Our study
offers new insight into the transcriptional regulation of the S100A12 gene.
PMID- 25110869
TI - Richter's transformation to diffuse large B-cell lymphoma: a retrospective study
reporting clinical data, outcome, and the benefit of adding rituximab to
chemotherapy, from the Israeli CLL Study Group.
AB - Richter's syndrome (RS) is the rare development of an aggressive lymphoid
malignancy in a patient with pre-existing chronic lymphocytic leukemia (CLL).
Data on RS is sparse and mostly derived from case reports or small series of
patients and only a few larger cohorts have been published. The purpose of this
large retrospective study was to summarize our national experience with RS in
CLL, examine possible risk factors, and analyze relevant demographic, laboratory
and clinical parameters, including results of therapy and outcome. We first
evaluated data obtained from 119 patients with RS diagnosed during 1971-2010 from
12 medical centers in Israel. The final cohort summarized consisted of 81
patients with RS who developed only diffuse large B-cell lymphoma (DLBCL) after
exclusion all cases with insufficient data and those who were not DLBCL. Median
overall survival from time of diagnosis of RS was 8 months; after applying the
Richter score, patients could be stratified into three prognostic groups, while
all other clinical and laboratory parameters evaluated had no prognostic
significance. Prior therapy for CLL had no impact on RS survival (P = 0.8) and
patients with therapy "naive" RS and those who had already received chemotherapy
prior to developing RS, had the same survival. The addition of rituximab to
chemotherapy for RS improved 2 years overall survival from 19% in the
chemotherapy alone arm to 42% (P value of 0.001). Although prognosis of patients
with RS remains dismal, this retrospective observation provides support for the
use of chemo-immunotherapy in DLBCL-RS.
PMID- 25110870
TI - Graphene oxide and laponite composite films with high oxygen-barrier properties.
AB - The design and fabrication of oxygen barrier films is important for both
fundamental and industrial applications. We prepared three different thin films
composed of graphene oxide (GO) and laponite (LN), a typical low cost inorganic
clay, with the GO/LN volume ratios of 1.9/0.1, 1.7/0.3 and 1.5/0.5 together with
a double layer film of the GO and LN. We found that the films with GO/LN =
1.9/0.1 and the double layers exhibited high oxygen barrier and oxygen
transmission rate values that reached 0.55 and 0.37 cm(3) per m(2) per atm per
day, respectively, which were much lower than those of the films prepared from
the pure GO, only LN and GO/LN = 1.7/0.3 and 1.5/0.5. This study is important for
the design and fabrication of a film from GO-based all inorganic nanomaterials
for applications in gas-barrier membranes.
PMID- 25110871
TI - Endoscopist Fatigue May Contribute to a Decline in the Effectiveness of Screening
Colonoscopy.
AB - GOALS: To assess whether endoscopist fatigue adversely affects the adenoma
detection rate (ADR) during screening colonoscopy. BACKGROUND: Endoscopist
fatigue may affect the ADR during colonoscopy; however, this association has not
been directly studied. STUDY: A prospective, multi-center study was performed on
screening colonoscopies performed for asymptomatic subjects between March 2012
and December 2012 in Korea. Endoscopist fatigue was defined and measured by
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire.
The ADR was compared between fatigued endoscopists and nonfatigued endoscopists,
and a multivariate regression analysis was performed to identify independent
factors related to the detection of colorectal adenoma. RESULTS: During the study
period, a total of 457 subjects underwent screening colonoscopy. After excluding
62 subjects, outcomes of 395 subjects were analyzed. The overall ADR of the study
population was 39.7%. The mean score of FACIT-F was 36.4+/-10.8, and a cutoff
score of 25 was chosen to define fatigue. The ADR was lower in fatigued
endoscopists than nonfatigued endoscopists (25.0% vs. 42.6%, P=0.008). Using
multivariate regression analysis, endoscopist fatigue measured with FACIT-F (odds
ratio=3.585; 95% confidence interval, 1.663-7.728; P=0.001) was found to be an
independent factor for the ADR. CONCLUSIONS: FACIT-F score may be a novel measure
for endoscopist fatigue, and ADR was adversely influenced by endoscopist fatigue
measured by FACIT-F. Our results suggest that endoscopist fatigue may contribute
to a decline in the effectiveness of screening colonoscopy.
PMID- 25110872
TI - Esophageal Stenting With Sutures: Time to Redefine Our Standards?
AB - BACKGROUND AND STUDY AIMS: Migration is the most common complication of the fully
covered metallic self-expanding esophageal stent (FCSEMS). Recent studies have
demonstrated migration rates between 30% and 60%. The aim of this study was to
determine the effect of fixation of the FCSEMS by endoscopic suturing on
migration rate. PATIENT AND METHODS: Patients who underwent stent placement for
esophageal strictures and leaks over the last year were captured and reviewed
retrospectively. Group A, cases, were patients who underwent suture placement and
group B, controls, were patients who had stents without sutures. Basic
demographics, indications, and adverse events (AEs) were collected. Kaplan-Meier
analysis and Cox regression modeling were conducted to determine estimates and
predictors of stent migration in patients with and without suture placement.
RESULTS: Thirty-seven patients (18 males, 48.65%), mean age 57.2 years (+/-16.3
y), were treated with esophageal FCSEMS. A total of 17 patients received sutures
(group A) and 20 patients received stents without sutures (group B). Stent
migration was noted in a total of 13 of the 37 patients (35%) [2 (11%) in group A
and 11 (55%) in group B]. Using Kaplan-Meier analysis and log-rank analysis,
fixation of the stent with suturing reduced the risk of migration (P=0.04). There
were no AEs directly related to suture placement. CONCLUSIONS: Anchoring of the
upper flare of the FCSEMS with endoscopic sutures is technically feasible and
significantly reduces stent migration rate when compared with no suturing, and is
a safe procedure with very low AEs rates.
PMID- 25110867
TI - Small-molecule inhibitors of the receptor tyrosine kinases: promising tools for
targeted cancer therapies.
AB - Chemotherapeutic and cytotoxic drugs are widely used in the treatment of cancer.
In spite of the improvements in the life quality of patients, their effectiveness
is compromised by several disadvantages. This represents a demand for developing
new effective strategies with focusing on tumor cells and minimum side effects.
Targeted cancer therapies and personalized medicine have been defined as a new
type of emerging treatments. Small molecule inhibitors (SMIs) are among the most
effective drugs for targeted cancer therapy. The growing number of approved SMIs
of receptor tyrosine kinases (RTKs) i.e., tyrosine kinase inhibitors (TKIs) in
the clinical oncology imply the increasing attention and application of these
therapeutic tools. Most of the current approved RTK-TKIs in preclinical and
clinical settings are multi-targeted inhibitors with several side effects. Only a
few specific/selective RTK-TKIs have been developed for the treatment of cancer
patients. Specific/selective RTK-TKIs have shown less deleterious effects
compared to multi-targeted inhibitors. This review intends to highlight the
importance of specific/selective TKIs for future development with less side
effects and more manageable agents. This article provides an overview of: (1) the
characteristics and function of RTKs and TKIs; (2) the recent advances in the
improvement of specific/selective RTK-TKIs in preclinical or clinical settings;
and (3) emerging RTKs for targeted cancer therapies by TKIs.
PMID- 25110873
TI - The role of domperidone in increasing the completion rate of small bowel capsule
endoscopy: how should it be used?
PMID- 25110874
TI - Identifying all at-risk patients for Clostridium difficile infection.
PMID- 25110875
TI - Lynch-like syndrome: characterization and comparison with EPCAM deletion
carriers.
AB - Colorectal cancers (CRCs) with microsatellite instability-high (MSI+) but without
detectable germline mutation or hypermethylation in DNA mismatch repair (MMR)
genes can be classified as Lynch-like syndrome (LLS). The underlying mechanism
and clinical significances of LLS are largely unknown. We measured MSI and MMR
protein expression in 4,765 consecutive CRC cases. Among these, MSI+ cases were
further classified based on clinical parameters, germline sequencing of MMR genes
or polymerase epsilon (POLE) and delta (POLD1) and promoter methylation analysis
of MLH1 and MSH2. We found that MSI+ and MMR protein-deficient CRCs comprised
6.3% (N = 302) of this cohort. On the basis of germline sequencing of 124 cases,
we identified 54 LS with MMR germline mutation (LS-MMR), 15 LS with EPCAM
deletions (LS-EPCAM) and 55 LLS patients. Of the 55 LLS patients, six (10.9%) had
variants of unknown significance in the genes tested, and one patient had a novel
somatic mutation (p.S459P) in POLE. In patients with biallelic deletions of
EPCAM, all tumors and their matched normal mucosa showed promoter
hypermethylation of MSH2. Finally, we found that patients with LLS and LS-EPCAM
shared clinical features that differed from LS-MMR patients, including lower
frequency of fulfillment of the revised Bethesda guidelines (83.6 and 86.7% vs.
98.1% for LS-MMR) and older mean age at CRC diagnosis (52.6 and 52.7 years vs.
43.9 years for LS-MMR). We identified somatic mutation in POLE as a rare
underlying cause for MMR deficiency in LLS. The similarity between LLS and LS
EPCAM suggests LLS as a subset of familial MSI+ CRC.
PMID- 25110876
TI - Hematopoietic stem cell transplantation of an adolescent with neurological
manifestations of homozygous missense PRF1 mutation.
AB - Individuals with biallelic truncating PRF1 mutations typically present with
fulminant early-onset familial hemophagocytic lymphohistiocytosis (FHL). We
report a 19-year-old male with a 5-year history of recurrent fever and headaches
progressing to refractory seizures. Brain imaging revealed multiple ring
enhancing lesions. Laboratory investigations demonstrated that the patient
displayed defective lymphocyte cytotoxicity and carried a homozygous missense
PRF1 mutation, c.394G > A (p.Gly132Arg). The patient was successfully treated
with chemo-immunotherapy followed by matched related allogeneic hematopoietic
stem cell transplantation (HSCT). Our findings demonstrate that prompt HSCT of
late-onset FHL with primarily neurological manifestation can reverse central
nervous system symptoms and improve long-term outcome.
PMID- 25110877
TI - Cyclotrimerization of arylalkynes on Au(111).
AB - Surface-assisted cyclotrimerization of arylalkynes was studied on Au(111) by
means of scanning tunneling microscopy (STM) under ultra-high vacuum (UHV)
conditions. Upon thermal activation, cyclotrimerization of 1,3,5-tris-(4
ethynylphenyl)benzene proceeds readily and with high selectivity, and results in
two-dimensional covalently bonded polyphenylene nanostructures exhibiting a
honeycomb topology.
PMID- 25110878
TI - Hospital relationships with direct-to-consumer screening companies.
PMID- 25110879
TI - Cancer family caregiver depression: are religion-related variables important?
AB - OBJECTIVE: Prevalence estimates for clinical depression among cancer family
caregivers (CFC) range upwards to 39%. Research inconsistently reports risk for
CFC depressive symptoms when evaluating age, gender, ethnicity, or length of time
as caregiver. The discrepant findings, coupled with emerging literature
indicating religiosity may mitigate depression in some populations, led us to
investigate religion-related variables to help predict CFC depressive symptoms.
METHODS: We conducted a cross-sectional study of 150 CFC. Explanatory variables
included age, gender, spousal status, length of time as caregiver, attendance at
religious services, and prayer. The outcome variable was the Center for
Epidemiological Studies Depression Scale score. RESULTS: Compared with large
national and state datasets, our sample has lower representation of individuals
with no religious affiliation (10.7% vs. 16.1% national, p = 0.07 and 23.0%
state, p = 0.001), higher rate of attendance at religious services (81.3% vs.
67.2% national, p < 0.001 and 30.0% state, p < 0.001), and higher rate of prayer
(65.3% vs. 42.9% national, p < 0.001; no state data available). In unadjusted and
adjusted models, prayer is not significantly associated with caregiver depressive
symptoms or clinically significant depressive symptomology. Attendance at
religious services is associated with depressive symptoms (p = 0.004) with an
inversely linear trend (p = 0.002). CONCLUSION: The significant inverse
association between attendance at religious services and depressive symptoms,
despite no association between prayer and depressive symptoms, indicates that
social or other factors may accompany attendance at religious services and
contribute to the association. Clinicians can consider supporting a CFC's
attendance at religious services as a potential preventive measure for depressive
symptoms.
PMID- 25110880
TI - Contribution of human immunodeficiency virus type 1 minority variants to reduced
drug susceptibility in patients on an integrase strand transfer inhibitor-based
therapy.
AB - The role of HIV-1 minority variants on transmission, pathogenesis, and virologic
failure to antiretroviral regimens has been explored; however, most studies of
low-level HIV-1 drug-resistant variants have focused in single target regions.
Here we used a novel HIV-1 genotypic assay based on deep sequencing, DEEPGEN
(Gibson et al 2014 Antimicrob Agents Chemother 58?2167) to simultaneously analyze
the presence of minority variants carrying mutations associated with reduced
susceptibility to protease (PR), reverse transcriptase (RT), and integrase strand
transfer integrase inhibitors (INSTIs), as well as HIV-1 coreceptor tropism. gag
p2/NCp7/p1/p6/pol-PR/RT/INT and env/C2V3 PCR products were obtained from twelve
heavily treatment-experienced patients experiencing virologic failure while
participating in a 48-week dose-ranging study of elvitegravir (GS-US-183-0105).
Deep sequencing results were compared with (i) virological response to treatment,
(ii) genotyping based on population sequencing, (iii) phenotyping data using
PhenoSense and VIRALARTS, and (iv) HIV-1 coreceptor tropism based on the
phenotypic test VERITROP. Most patients failed the antiretroviral regimen with
numerous pre-existing mutations in the PR and RT, and additionally newly acquired
INSTI-resistance mutations as determined by population sequencing (mean 9.4, 5.3,
and 1.4 PI- RTI-, and INSTI-resistance mutations, respectively). Interestingly,
since DEEPGEN allows the accurate detection of amino acid substitutions at
frequencies as low as 1% of the population, a series of additional drug
resistance mutations were detected by deep sequencing (mean 2.5, 1.5, and 0.9,
respectively). The presence of these low-abundance HIV-1 variants was associated
with drug susceptibility, replicative fitness, and coreceptor tropism determined
using sensitive phenotypic assays, enhancing the overall burden of resistance to
all four antiretroviral drug classes. Further longitudinal studies based on deep
sequencing tests will help to clarify (i) the potential impact of minority HIV-1
drug resistant variants in response to antiretroviral therapy and (ii) the
importance of the detection of HIV minority variants in the clinical practice.
PMID- 25110881
TI - Acquisition of Cry1Ac protein by non-target arthropods in Bt soybean fields.
AB - Soybean tissue and arthropods were collected in Bt soybean fields in China at
different times during the growing season to investigate the exposure of
arthropods to the plant-produced Cry1Ac toxin and the transmission of the toxin
within the food web. Samples from 52 arthropod species/taxa belonging to 42
families in 10 orders were analysed for their Cry1Ac content using enzyme-linked
immunosorbent assay (ELISA). Among the 22 species/taxa for which three samples
were analysed, toxin concentration was highest in the grasshopper Atractomorpha
sinensis and represented about 50% of the concentration in soybean leaves. Other
species/taxa did not contain detectable toxin or contained a concentration that
was between 1 and 10% of that detected in leaves. These Cry1Ac-positive
arthropods included a number of mesophyll-feeding Hemiptera, a cicadellid, a
curculionid beetle and, among the predators, a thomisid spider and an
unidentified predatory bug belonging to the Anthocoridae. Within an arthropod
species/taxon, the Cry1Ac content sometimes varied between life stages
(nymphs/larvae vs. adults) and sampling dates (before, during, and after
flowering). Our study is the first to provide information on Cry1Ac-expression
levels in soybean plants and Cry1Ac concentrations in non-target arthropods in
Chinese soybean fields. The data will be useful for assessing the risk of non
target arthropod exposure to Cry1Ac in soybean.
PMID- 25110882
TI - Identification of candidate genes associated with leaf senescence in cultivated
sunflower (Helianthus annuus L.).
AB - Cultivated sunflower (Helianthus annuus L.), an important source of edible
vegetable oil, shows rapid onset of senescence, which limits production by
reducing photosynthetic capacity under specific growing conditions. Carbon for
grain filling depends strongly on light interception by green leaf area, which
diminishes during grain filling due to leaf senescence. Transcription factors
(TFs) regulate the progression of leaf senescence in plants and have been well
explored in model systems, but information for many agronomic crops remains
limited. Here, we characterize the expression profiles of a set of putative
senescence associated genes (SAGs) identified by a candidate gene approach and
sunflower microarray expression studies. We examined a time course of sunflower
leaves undergoing natural senescence and used quantitative PCR (qPCR) to measure
the expression of 11 candidate genes representing the NAC, WRKY, MYB and NF-Y TF
families. In addition, we measured physiological parameters such as chlorophyll,
total soluble sugars and nitrogen content. The expression of Ha-NAC01, Ha-NAC03,
Ha-NAC04, Ha-NAC05 and Ha-MYB01 TFs increased before the remobilization rate
increased and therefore, before the appearance of the first physiological
symptoms of senescence, whereas Ha-NAC02 expression decreased. In addition, we
also examined the trifurcate feed-forward pathway (involving ORE1, miR164, and
ethylene insensitive 2) previously reported for Arabidopsis. We measured
transcription of Ha-NAC01 (the sunflower homolog of ORE1) and Ha-EIN2, along with
the levels of miR164, in two leaves from different stem positions, and identified
differences in transcription between basal and upper leaves. Interestingly, Ha
NAC01 and Ha-EIN2 transcription profiles showed an earlier up-regulation in upper
leaves of plants close to maturity, compared with basal leaves of plants at pre
anthesis stages. These results suggest that the H. annuus TFs characterized in
this work could play important roles as potential triggers of leaf senescence and
thus can be considered putative candidate genes for senescence in sunflower.
PMID- 25110884
TI - Increased secretory leukocyte protease inhibitor (SLPI) production by highly
metastatic mouse breast cancer cells.
AB - The precise molecular mechanisms enabling cancer cells to metastasize from the
primary tumor to different tissue locations are still largely unknown. Secretion
of some proteins by metastatic cells could facilitate metastasis formation. The
comparison of secreted proteins from cancer cells with different metastatic
capabilities in vivo might provide insight into proteins involved in the
metastatic process. Comparison of the secreted proteins from the mouse breast
cancer cell line 4T1 and its highly metastatic 4T1.2 clone revealed a prominent
differentially secreted protein which was identified as SLPI (secretory leukocyte
protease inhibitor). Western blotting indicated higher levels of the protein in
both conditioned media and whole cell lysates of 4T1.2 cells. Additionally higher
levels of SLPI were also observed in 4T1.2 breast tumors in vivo following
immunohistochemical staining. A comparison of SLPI mRNA levels by gene profiling
using microarrays and RT-PCR did not detect major differences in SLPI gene
expression between the 4T1 and 4T1.2 cells indicating that SLPI secretion is
regulated at the protein level. Our results demonstrate that secretion of SLPI is
drastically increased in highly metastatic cells, suggesting a possible role for
SLPI in enhancing the metastatic behavior of breast cancer cell line 4T1.
PMID- 25110883
TI - Genome-wide modulation of gene transcription in ovarian carcinoma cells by a new
mithramycin analogue.
AB - Ovarian cancer has a poor prognosis due to intrinsic or acquired resistance to
some cytotoxic drugs, raising the interest in new DNA-binding agents such as
mithramycin analogues as potential chemotherapeutic agents in gynecological
cancer. Using a genome-wide approach, we have analyzed gene expression in A2780
human ovarian carcinoma cells treated with the novel mithramycin analogue DIG-MSK
(demycarosyl-3D-beta-D-digitoxosyl-mithramycin SK) that binds to C+G-rich DNA
sequences. Nanomolar concentrations of DIG-MSK abrogated the expression of genes
involved in a variety of cell processes including transcription regulation and
tumor development, which resulted in cell death. Some of those genes have been
associated with cell proliferation and poor prognosis in ovarian cancer. Sp1
transcription factor regulated most of the genes that were down-regulated by the
drug, as well as the up-regulation of other genes mainly involved in response to
cell stress. The effect of DIG-MSK in the control of gene expression by other
transcription factors was also explored. Some of them, such as CREB, E2F and
EGR1, also recognize C/G-rich regions in gene promoters, which encompass
potential DIG-MSK binding sites. DIG-MSK affected several biological processes
and molecular functions related to transcription and its cellular regulation in
A2780 cells, including transcription factor activity. This new compound might be
a promising drug for the treatment of ovarian cancer.
PMID- 25110885
TI - Quantum-classical calculation of the absorption and emission spectral shapes of
oligothiophenes at low and room temperature by first-principle calculations.
AB - We report a thorough computational characterization of the low- and room
temperature absorption and emission spectra of a series of oligothiophenes that
contain between three and seven thiophene units. Our computational approach is
based on time-dependent (TD) density functional calculations with the CAM-B3LYP
functional. The effect of vibrations is included without resorting to any
empirical parameters either at a fully quantum level or with a hybrid quantum
classical protocol. This latter approach is introduced to describe the relevant
broadening effects in absorption at room temperature and is based on the
partition of the vibrational modes into two sets: the inter-ring torsions treated
at the anharmonic level in a classical way and the remaining modes described at
the quantum level. The contribution of the quantum modes to the spectrum is
computed by using a harmonic approximation, which accounts for Duschinsky mixing
and changes in the vibrational frequencies associated with the electronic
transition; a path-integral TD approach is adopted to account for the effect of
temperature. The spectra simulated at low temperatures are in very good agreement
with their experimental counterparts, which indicates that our calculations can
quantitatively reproduce the effect of chain lengthening on the position and the
shape of the spectra. Good agreement is also obtained at room temperature, for
which we show that the classical description of the broadening, owing to the
inter-ring torsions, reproduces the loss of the vibronic structure observed in
the experiment and introduces only a slight overestimation of the spectral width.
PMID- 25110886
TI - The effects of genetic variation in FTO rs9939609 on obesity and dietary
preferences in Chinese Han children and adolescents.
AB - The association of the rs9939609 single nucleotide polymorphism in FTO gene with
obesity has been extensively investigated in studies of populations of European,
African, and Asian ancestry. However, inconsistent results have been reported in
Asian populations, and the relationship of FTO variation and dietary behaviors
has only rarely been examined in Chinese children and adolescents. The aim of
this study was to assess the association of rs9939609 with obesity and dietary
preferences in childhood in a Chinese population. Epidemiological data including
dietary preferences were collected in interviews using survey questionnaires, and
rs9939609 genotype was determined by real-time PCR. The associations of rs9939609
genotypes with obesity and dietary preferences were analyzed by multivariate
logistic regression using both additive and dominant models. The results showed
that subjects with a TA or AA genotype had an increased risk of obesity compared
with the TT participants; the odds ratios (ORs) were 1.47 (95% CI: 1.25-1.71, P =
1.73*10-6), and 3.32 (95% CI: 2.01-5.47, P = 2.68*10-6), respectively. After
adjusting for age and gender, body mass index, waist circumference, hip
circumference, systolic blood pressure, diastolic blood pressure, fasting blood
glucose, triglycerides, and low-density lipoprotein cholesterol were higher, and
high-density lipoprotein cholesterol was lower in TA and AA participants than in
those with the TT genotype. After additionally controlling for body mass index,
the association remained significant only for systolic blood pressure (P =
0.005). Compared with TT participants, those with the AA genotype were more
likely to prefer a meat-based diet (OR = 2.81, 95% CI: 1.52-5.21). The combined
OR for obesity in participants with TA/AA genotypes and preference for a meat
based diet was 4.04 (95% CI: 2.8-5.81) compared with the TT participants who
preferred a plant-based diet. These findings indicate the genetic variation of
rs9939609 is associated with obesity and dietary preferences in Chinese children
and adolescents.
PMID- 25110887
TI - Functional validation and comparison framework for EIT lung imaging.
AB - INTRODUCTION: Electrical impedance tomography (EIT) is an emerging clinical tool
for monitoring ventilation distribution in mechanically ventilated patients, for
which many image reconstruction algorithms have been suggested. We propose an
experimental framework to assess such algorithms with respect to their ability to
correctly represent well-defined physiological changes. We defined a set of
clinically relevant ventilation conditions and induced them experimentally in 8
pigs by controlling three ventilator settings (tidal volume, positive end
expiratory pressure and the fraction of inspired oxygen). In this way, large and
discrete shifts in global and regional lung air content were elicited. METHODS:
We use the framework to compare twelve 2D EIT reconstruction algorithms,
including backprojection (the original and still most frequently used algorithm),
GREIT (a more recent consensus algorithm for lung imaging), truncated singular
value decomposition (TSVD), several variants of the one-step Gauss-Newton
approach and two iterative algorithms. We consider the effects of using a 3D
finite element model, assuming non-uniform background conductivity, noise
modeling, reconstructing for electrode movement, total variation (TV)
reconstruction, robust error norms, smoothing priors, and using difference vs.
normalized difference data. RESULTS AND CONCLUSIONS: Our results indicate that,
while variation in appearance of images reconstructed from the same data is not
negligible, clinically relevant parameters do not vary considerably among the
advanced algorithms. Among the analysed algorithms, several advanced algorithms
perform well, while some others are significantly worse. Given its vintage and ad
hoc formulation backprojection works surprisingly well, supporting the validity
of previous studies in lung EIT.
PMID- 25110888
TI - Human-induced changes in landscape configuration influence individual movement
routines: lessons from a versatile, highly mobile species.
AB - Landscape conversion by humans may have detrimental effects on animal populations
inhabiting managed ecosystems, but human-altered areas may also provide suitable
environments for tolerant species. We investigated the spatial ecology of a
highly mobile nocturnal avian species-the red-necked nightjar (Caprimulgus
ruficollis)-in two contrastingly managed areas in Southwestern Spain to provide
management recommendations for species having multiple habitat requirements.
Based on habitat use by radiotagged nightjars, we created maps of functional
heterogeneity in both areas so that the movements of breeding individuals could
be modeled using least-cost path analyses. In both the natural and the managed
area, nightjars used remnants of native shrublands as nesting sites, while
pinewood patches (either newly planted or natural mature) and roads were selected
as roosting and foraging habitats, respectively. Although the fraction of
functional habitat was held relatively constant (60.9% vs. 74.1% in the natural
and the managed area, respectively), landscape configuration changed noticeably.
As a result, least-cost routes (summed linear distances) from nest locations to
the nearest roost and foraging sites were three times larger in the natural than
in the managed area (mean +/- SE: 1356+/-76 m vs. 439+/-32 m). It seems likely
that the increased proximity of functional habitats in the managed area relative
to the natural one is underlying the significantly higher abundances of nightjars
observed therein, where breeders should travel shorter distances to link together
essential resources, thus likely reducing their energy expenditure and mortality
risks. Our results suggest that landscape configuration, but not habitat
availability, is responsible for the observed differences between the natural and
the managed area in the abundance and movements of breeding nightjars, although
no effect on body condition was detected. Agricultural landscapes could be
moderately managed to preserve small native remnants and to favor the
juxtaposition of functional habitats to benefit those farm species relying on
patchy resources.
PMID- 25110891
TI - Gene knockout and overexpression analysis revealed the role of N-acetylmuramidase
in autolysis of Lactobacillus delbrueckii subsp. bulgaricus ljj-6.
AB - Autolysis of lactic acid bacteria (LAB) plays a vital role in dairy processing.
During cheese making, autolysis of LAB affects cheese flavor development through
release of intracellular enzymes and restricts the proliferation of cells in
yogurt fermentation and probiotics production. In order to explore the mechanism
of autolysis, the gene for the autolytic enzymes of L. bulgaricus, N
acetylmuramidase (mur), was cloned and sequenced (GenBank accession number:
KF157911). Mur gene overexpression and gene knockout vectors were constructed
based on pMG76e and pUC19 vectors. Recombinant plasmids were transformed into L.
bulgaricus ljj-6 by electroporation, then three engineered strains with pMG76e
mur vector and fifteen engineered strains with pUC19-mur::EryBII were screened.
The autolysis of the mur knockout strain was significantly lower and autolysis of
the mur overexpressed strain was significantly higher compared with that of the
wild type strain ljj-6. This result suggested that the mur gene played an
important role in autolysis of L. bulgaricus. On the other hand, autolytic
activity in a low degree was still observed in the mur knockout strain, which
implied that other enzymes but autolysin encoded by mur were also involved in
autolysis of L. bulgaricus.
PMID- 25110892
TI - Societal cost of skin cancer in Sweden in 2011.
PMID- 25110893
TI - Curcumin improves hypoxia induced dysfunctions in 3T3-L1 adipocytes by protecting
mitochondria and down regulating inflammation.
AB - Obesity induced metabolic syndrome is increasing worldwide at an alarming rate.
It is characterized by excessive expansion of white adipose tissue which leads to
hypoxia and impairs normal metabolism. Recent studies reveal that hypoxia could
be one of the factors for inflammation, insulin resistance and other obesity
related complications. There is a high demand for anti-obese phytoceuticals to
control and manage the complications resulting from obesity. In this study, we
investigated how hypoxia affect the physiological functions of 3T3-L1 adipocytes
emphasizing on oxidative stress, inflammation, and mitochondrial functions. We
also evaluated the protective role of various doses of curcumin, a well-known
dietary antioxidant, on hypoxia induced alterations. The results revealed that
hypoxia significantly altered the vital parameters of adipocyte biology like HIF
1alpha expression (103.47% ?), lactate, and glycerol release (184.34% and 69.1%
?, respectively), reactive oxygen species production (432.53% ?), lipid and
protein oxidation (376.6% and 566.6% ?, respectively), reduction in antioxidant
enzymes (superoxide dismutase and catalase) status, secretion of inflammatory
markers (TNF alpha, IL 6, IL 1beta, and IFN gamma), and mitochondrial functions
(mitochondrial mass, membrane potential, permeability transition pore integrity,
and superoxide generation). Curcumin substantially protected adipocytes from
toxic effects of hypoxia in a dose dependent manner by protecting mitochondria
and down regulating inflammation. Acriflavine is used as a positive control. A
detailed investigation is required for the development of curcumin as an
effective nutraceutical against obesity.
PMID- 25110896
TI - Fabrication of nickel-foam-supported layered zinc-cobalt hydroxide nanoflakes for
high electrochemical performance in supercapacitors.
AB - Nickel foam supported Zn-Co hydroxide nanoflakes were fabricated by a facile
solvothermal method. Benefited from the unique structure of Zn-Co hydroxide
nanoflakes on a nickel foam substrate, the as prepared materials exhibited an
excellent specific capacitance of 901 F g(-1) at 5 A g(-1) and remarkable cycling
stability as electrode materials in supercapacitors.
PMID- 25110897
TI - Host-guest chemistry of a water-soluble pillar[5]arene: evidence for an ionic
exchange recognition process and different complexation modes.
AB - The complexation of an anionic guest by a cationic water-soluble pillararene is
reported. Isothermal titration calorimetry (ITC), (1)H NMR, (1)H and (19)F DOSY,
and STD NMR experiments were performed to characterize the complex formed under
aqueous neutral conditions. The results of ITC and (1)H NMR analyses showed the
inclusion of the guest inside the cavity of the pillar[5]arene, with the binding
constant and thermodynamic parameters influenced by the counter ion of the
macrocycle. NMR diffusion experiments showed that although a fraction of the
counter ions are expelled from the host cavity by exchange with the guest, a
complex with both counter ions and the guest inside the pillararene is formed.
The results also showed that at higher concentrations of guest in solution, in
addition to the inclusion of one guest molecule in the cavity, the pillararene
can also form an external complex with a second guest molecule.
PMID- 25110898
TI - Effects of the relative values of alternatives on preference for free-choice in
humans.
AB - Organisms often prefer conditions that allow selection among alternatives (free
choice) to conditions that do not (forced-choice), particularly when response
alternatives in free-choice produce equal or greater reinforcer magnitudes than
those available under forced-choice. We present data on free-choice preference
for human participants who gained or lost points by selecting images of cards on
a computer screen under a concurrent-chains schedule. Responding during the
initial link gained access to a terminal link offering a single-card set (forced
choice) or a three-card set (free-choice). The alternatives in free-choice
produced reinforcer magnitudes (points) that were: (a) equal to forced-choice;
(b) equal to and greater than forced-choice; and (c) equal to and less than
forced-choice. Participants showed reliable preference for free-choice under some
conditions; however, preference decreased as reinforcer magnitude for some
alternatives in free-choice was reduced. This occurred even though it was
possible to obtain the same number of points across free- and forced-choice.
Although preference for free-choice was clearly demonstrated, the effect of
points available in the terminal link suggests that this phenomenon is subject to
modulation by other processes, such as reinforcement or punishment by obtained
outcomes in the terminal link. Context (reinforcer-gain or -loss) was not a
reliable predictor of preference.
PMID- 25110899
TI - Prevalence of anginal symptoms and myocardial ischemia and their effect on
clinical outcomes in outpatients with stable coronary artery disease: data from
the International Observational CLARIFY Registry.
AB - IMPORTANCE: In the era of widespread revascularization and effective
antianginals, the prevalence and prognostic effect of anginal symptoms and
myocardial ischemia among patients with stable coronary artery disease (CAD) are
unknown. OBJECTIVE: To describe the current clinical patterns among patients with
stable CAD and the association of anginal symptoms or myocardial ischemia with
clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: The Prospective
Observational Longitudinal Registry of Patients With Stable Coronary Artery
Disease (CLARIFY) registry enrolled outpatients in 45 countries with stable CAD
in 2009 to 2010 with 2-year follow-up (median, 24.1 months; range, 1 day to 3
years). Enrollees included 32 105 outpatients with prior myocardial infarction,
chest pain, and evidence of myocardial ischemia, evidence of CAD on angiography,
or prior revascularization. Of these, 20 291 (63.2%) had undergone a noninvasive
test for myocardial ischemia within 12 months of enrollment and were categorized
into one of the following 4 groups: no angina or ischemia (n = 13 207 [65.1%]);
evidence of myocardial ischemia without angina (silent ischemia) (n = 3028
[14.9%]); anginal symptoms alone (n = 1842 [9.1%]); and angina and ischemia (n =
2214 [10.9%]). EXPOSURES: Stable CAD. MAIN OUTCOME AND MEASURE: The composite of
cardiovascular (CV)-related death or nonfatal myocardial infarction. RESULTS:
Overall, 4056 patients (20.0%) had anginal symptoms and 5242 (25.8%) had evidence
of myocardial ischemia on results of noninvasive testing. Of 469 CV-related
deaths or myocardial infarctions, 58.2% occurred in patients without angina or
ischemia, 12.4% in patients with ischemia alone, 12.2% in patients with angina
alone, and 17.3% in patients with both. The hazard ratios for the primary outcome
relative to patients without angina or ischemia and adjusted for age, sex,
geographic region, smoking status, hypertension, diabetes mellitus, and
dyslipidemia were 0.90 (95% CI, 0.68-1.20; P = .47) for ischemia alone, 1.45 (95%
CI, 1.08-1.95; P = .01) for angina alone, and 1.75 (95% CI, 1.34-2.29; P < .001)
for both. Similar findings were observed for CV-related death and for fatal or
nonfatal myocardial infarction. CONCLUSIONS AND RELEVANCE: In outpatients with
stable CAD, anginal symptoms (with or without ischemia on noninvasive testing)
but not silent ischemia appear to be associated with an increased risk for
adverse CV outcomes. Most CV events occurred in patients without angina or
ischemia. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN43070564.
PMID- 25110900
TI - Smooth muscle cell phenotypic switch: implications for foam cell formation.
AB - PURPOSE OF REVIEW: It is well accepted that LDLs and its modified form oxidized
LDL (ox-LDL) play a major role in the development of atherosclerosis and foam
cell formation. Whereas the majority of these cells have been demonstrated to be
derived from macrophages, smooth muscle cells (SMCs) give rise to a significant
number of foam cells as well. During atherosclerotic plaque formation, SMCs
switch from a contractile to a synthetic phenotype. The contribution of this
process to foam cell formation is still not well understood. RECENT FINDINGS: It
has been confirmed that a large proportion of foam cells in human atherosclerotic
plaques and in experimental intimal thickening arise from SMCs. SMC-derived foam
cells express receptors involved in ox-LDL uptake and HDL reverse transport. In
vitro studies show that treatment of SMCs with ox-LDL induces typical foam-cell
formation; this process is associated with a transition of SMCs toward a
synthetic phenotype. SUMMARY: This review summarizes data regarding the
phenotypic switch of arterial SMCs within atherosclerotic lesion and their
contribution to intimal foam cell formation.
PMID- 25110902
TI - Characterizing Social and Recreational Programming in Assisted Living.
AB - The objectives of this three-phased investigation were to (1) characterize
existing recreational programming opportunities for tenants residing in assisted
living (AL) and (2) gather perceptions on factors influencing activity program
planning and delivery. Using an integrated knowledge translation framework during
a one-year collaboration, we targeted 51 publicly funded AL sites from two health
authorities in British Columbia. We conducted an activity calendar review, staff
survey, and interactive symposia to identify factors that enabled or restricted
recreational programming. From the information obtained, we determined that all
AL sites delivered recreational programming. Although exercise and physical
activity opportunities were perceived as having high importance, most activities
were social. Staff reported confidence in delivering this type of programming and
believed it met the holistic needs of tenants, including their mental well-being,
and fostered a sense of community. Future avenues for increasing physical
activity of AL tenants should address individual, site, and organizational
characteristics.
PMID- 25110901
TI - PCSK9 and LDLR degradation: regulatory mechanisms in circulation and in cells.
AB - PURPOSE OF REVIEW: Proprotein convertase subtilisin/kexin type-9 (PCSK9) binds to
LDL receptor (LDLR) and targets it for lysosomal degradation in cells. Decreased
hepatic clearance of plasma LDL-cholesterol is the primary gauge of PCSK9
activity in humans; however, PCSK9's evolutionary role may extend to other
lipoprotein classes and processes. This review highlights studies that are
providing novel insights into physiological regulation of PCSK9 transcription and
plasma PCSK9 activity. RECENT FINDINGS: Recent studies indicate that circulating
PCSK9 binds to apolipoprotein B100 on LDL particles, which in turn inhibits
PCSK9's ability to bind to cell surface LDLRs. Negative feedback of secreted
PCSK9 activity by LDL could serve to increase plasma excursion of triglyceride
rich lipoproteins and monitor lipoprotein remodeling. Recent findings have
identified hepatocyte nuclear factor-1alpha as a key transcriptional regulator
that cooperates with sterol regulatory element-binding protein-2 to control PCSK9
expression in hepatocytes in response to nutritional and hormonal inputs, as well
as acute inflammation. SUMMARY: PCSK9 is an established target for cholesterol
lowering therapies. Further study of PCSK9 regulatory mechanisms may identify
additional control points for pharmacological inhibition of PCSK9-mediated LDLR
degradation. PCSK9 function could reflect ancient roles in the fasting-feeding
cycle and in linking lipoprotein metabolism with innate immunity.
PMID- 25110903
TI - Modeling sparsely clustered data: design-based, model-based, and single-level
methods.
AB - Recent studies have investigated the small sample properties of models for
clustered data, such as multilevel models and generalized estimating equations.
These studies have focused on parameter bias when the number of clusters is
small, but very few studies have addressed the methods' properties with sparse
data: a small number of observations within each cluster. In particular, studies
have yet to address the properties of generalized estimating equations, a
possible alternative to multilevel models often overlooked in behavioral
sciences, with sparse data. This article begins with a discussion of population
averaged and cluster-specific models, provides a brief overview of both
multilevel models and generalized estimating equations, and then conducts a
simulation study on the sparse data properties of generalized estimating
equations, multilevel models, and single-level regression models for both normal
and binary outcomes. The simulation found generalized estimating equations
estimate regression coefficients and their standard errors without bias with as
few as 2 observations per cluster, provided that the number of clusters was
reasonably large. Similar to the previous studies, multilevel models tended to
overestimate the between-cluster variance components when the cluster size was
below about 5.
PMID- 25110904
TI - Combating unmeasured confounding in cross-sectional studies: evaluating
instrumental-variable and Heckman selection models.
AB - Unmeasured confounding is the principal threat to unbiased estimation of
treatment "effects" (i.e., regression parameters for binary regressors) in
nonexperimental research. It refers to unmeasured characteristics of individuals
that lead them both to be in a particular "treatment" category and to register
higher or lower values than others on a response variable. In this article, I
introduce readers to 2 econometric techniques designed to control the problem,
with a particular emphasis on the Heckman selection model (HSM). Both techniques
can be used with only cross-sectional data. Using a Monte Carlo experiment, I
compare the performance of instrumental-variable regression (IVR) and HSM to that
of ordinary least squares (OLS) under conditions with treatment and unmeasured
confounding both present and absent. I find HSM generally to outperform IVR with
respect to mean-square-error of treatment estimates, as well as power for
detecting either a treatment effect or unobserved confounding. However, both HSM
and IVR require a large sample to be fully effective. The use of HSM and IVR in
tandem with OLS to untangle unobserved confounding bias in cross-sectional data
is further demonstrated with an empirical application. Using data from the 2006
2010 General Social Survey (National Opinion Research Center, 2014), I examine
the association between being married and subjective well-being.
PMID- 25110905
TI - A comparison of procedures to test for moderators in mixed-effects meta
regression models.
AB - Several alternative methods are available when testing for moderators in mixed
effects meta-regression models. A simulation study was carried out to compare
different methods in terms of their Type I error and statistical power rates. We
included the standard (Wald-type) test, the method proposed by Knapp and Hartung
(2003) in 2 different versions, the Huber-White method, the likelihood ratio
test, and the permutation test in the simulation study. These methods were
combined with 7 estimators for the amount of residual heterogeneity in the effect
sizes. Our results show that the standard method, applied in most meta-analyses
up to date, does not control the Type I error rate adequately, sometimes leading
to overly conservative, but usually to inflated, Type I error rates. Of the
different methods evaluated, only the Knapp and Hartung method and the
permutation test provide adequate control of the Type I error rate across all
conditions. Due to its computational simplicity, the Knapp and Hartung method is
recommended as a suitable option for most meta-analyses.
PMID- 25110906
TI - Uromodulin, an emerging novel pathway for blood pressure regulation and
hypertension.
PMID- 25110907
TI - Construction of carbon nanotube based nanoarchitectures for selective
impedimetric detection of cancer cells in whole blood.
AB - A carbon nanotube (CNT) based nanoarchitecture is developed for rapid, sensitive
and specific detection of cancer cells by using real time electrical impedance
sensing. The sensor is constructed with carbon nanotube (CNT) multilayers and
EpCAM (epithelial cell adhesion molecule) antibodies, which are assembled on an
indium tin oxide (ITO) electrode surface. The binding of tumor cells to EpCAM
antibodies causes increase of the electron-transfer resistance. The
electrochemical impedance of the prepared biosensors is linear with the logarithm
of concentration of the liver cancer cell line (HepG2) within the concentration
range of 10 to 10(5) cells per mL. The detection limit for HepG2 cells is 5 cells
per mL. The proposed impedimetric sensing devices allow for sensitive and
specific detection of cancer cells in whole-blood samples without any sample
pretreatment steps.
PMID- 25110908
TI - Influence of pseudophakic lens capsule opacification on spectral domain and time
domain optical coherence tomography image quality.
AB - PURPOSE: To evaluate the influence of posterior capsule opacification (PCO) on
optical coherence tomography (OCT) acquisition of macular retinal thickness (RT)
and volume using time domain OCT (TD-OCT) and spectral domain OCT (SD-OCT).
MATERIALS AND METHODS: We studied 37 eyes of 31 patients with PCO. Each patient
underwent an evaluation with TD-OCT and with SD-OCT before and after Nd:YAG
capsulotomy. We recorded RT and retinal volume in the macular area using only
good quality images. RESULTS: Best corrected visual acuity improved in all eyes
after Nd:YAG capsulotomy, with the degree of improvement ranging from 0.3 +/- 0.7
to 0.1 +/-0.7 (p = 0.01). Before the treatment, only 27% of the examinations were
valuable with TD-OCT, while using SD-OCT, it was possible to obtain an
examination of suitable quality both before and after the Yag laser capsulotomy
in 100% of the eyes. We did not observe significant differences between mean
preoperative and postoperative RT and total macular volume measurements, neither
with TD-OCT nor with SD-OCT. RT and total macular volume values obtained using TD
OCT were always lower than those obtained from the SD-OCT, both before and after
capsulotomy. CONCLUSIONS: Our study confirmed that with old generation TD-OCT,
PCO has a strong negative influence on the quality of OCT acquisition, and
examination is reliable only when it is possible to acquire good quality images.
With new generation SD-OCT, tomographic acquisitions are always reliable and are
not influenced by the presence of PCO.
PMID- 25110909
TI - Sleep-related eating disorder associated with quetiapine.
PMID- 25110911
TI - Research networks in primary care: an answer to the call for better clinical
research.
PMID- 25110912
TI - Adaptive Parent Population Sizing in Evolution Strategies.
AB - Adaptive population sizing aims at improving the overall progress of an evolution
strategy. At each generation, it determines the parental population size that
promises the largest fitness gain, based on the information collected during the
evolutionary process. In this paper, we develop an adaptive variant of a (MU/MU,
lambda) evolution strategy. Based on considerations on the sphere, we derive two
approaches for adaptive population sizing. We then test these approaches
empirically on the sphere model using a normalized mutation strength and
cumulative mutation strength adaption. Finally, we compare the methodology on
more general functions with a fixed population, covariance matrix adaption
evolution strategy (CMA-ES). The results confirm that our adaptive population
sizing methods yield better results than even the best fixed population size.
PMID- 25110913
TI - Vaginal Dryness and Beyond: The Sexual Health Needs of Women Diagnosed With
Metastatic Breast Cancer.
AB - While research on the sexual health of women with early stage cancer has grown
extensively over the past decade, markedly less information is available to
support the sexual health needs of women diagnosed with advanced breast cancer.
Semistructured interviews were conducted with 32 women diagnosed with metastatic
breast cancer (ages 35 to 77) about questions they had concerning their sexual
health and intimate relationships. All participants were recruited from a
comprehensive cancer center at a large Midwestern university. Three themes were
examined: the role of sexual activity and intimate touch in participants' lives,
unmet information needs about sexual health, and communication with medical
providers about sexual concerns. Findings indicated that sexual activities with
partners were important; however, participants worried about their own physical
limitations and reported frequent physical (e.g., bone pains) and vaginal pain
associated with intercourse. When women raised concerns about these issues in
clinical settings, medical providers often focused exclusively on vaginal
lubricants, which did not address the entirety of women's problems or concerns.
In addition, women diagnosed with metastatic breast cancer reported needing
additional resources about specialized vaginal lubricants, nonpenetrative and
nongenitally focused sex, and sexual positions that did not compromise their
physical health yet still provided pleasure.
PMID- 25110914
TI - trans-Platinum(II) complex of 3-aminoflavone - synthesis, X-ray crystal structure
and biological activities in vitro.
AB - This paper describes the synthesis of trans-bis-(3
aminoflavone)dichloridoplatinum(ii) (trans-Pt(3-af)2Cl2; TCAP) for use as a
potential anticancer compound, and the evaluation of its structure by elemental
and spectral analyses, and X-ray crystallography. The complex demonstrated a
significant cytotoxic effect against human and murine cancer cell lines, as well
as weaker toxicity towards healthy cells (human peripheral blood lymphocytes) in
comparison with cisplatin. Various biochemical and morphological methods confirm
that the proapoptotic activity of trans-Pt(3-af)2Cl2 is markedly higher than the
reference cisplatin. Our results suggest that trans-Pt(3-af)2Cl2 may have a
different antitumour specificity from that of cisplatin.
PMID- 25110915
TI - Altered innervation of the fallopian tube in adenomyosis.
PMID- 25110916
TI - MIDA as a simple and highly efficient ligand for palladium-catalyzed Hiyama cross
coupling of aryl halides.
AB - N-Methyliminodiacetic acid (MIDA) as a simple, air stable and water-soluble
ligand has been used in the palladium-catalyzed Hiyama cross-coupling reaction of
trimethoxyphenylsilane with aryl halides. The yield of the corresponding Hiyama
coupling products is high up to around 90% in water and isopropanol under an
ambient atmosphere in the presence of KOH and NaF.
PMID- 25110917
TI - Relative and absolute stereochemistry of diacarperoxides: antimalarial
norditerpene endoperoxides from marine sponge Diacarnus megaspinorhabdosa.
AB - Five new norditerpene endoperoxides, named diacarperoxides H-L (1-5), and a new
norditerpene diol, called diacardiol B (6), were isolated from the South China
Sea sponge, Diacarnus megaspinorhabdosa. Their structures, including
conformations and absolute configurations, were determined by using spectroscopic
analyses, computational approaches and chemical degradation. Diacarperoxides H-J
(1-3) showed some interesting stereochemical issues, as well as antimalarial
activity.
PMID- 25110918
TI - The skeletal amino acid composition of the marine demosponge Aplysina
cavernicola.
AB - It has been discovered during the past few years that demosponges of the order
Verongida such as Aplysina cavernicola exhibit chitin-based skeletons. Verongida
sponges are well known to produce bioactive brominated tyrosine derivatives. We
could recently demonstrate that brominated compounds do not exclusively occur in
the cellular matrix but also in the skeletons of the marine sponges Aplysina
cavernicola and Ianthella basta. Our measurements imply that these yet unknown
compounds are strongly, possibly covalently bound to the sponge skeletons. In the
present work, we determined the skeletal amino acid composition of the demosponge
A. cavernicola especially with respect to the presence of halogenated amino
acids. The investigations of the skeletons before and after MeOH extraction
confirmed that only a small amount of the brominated skeleton-bound compounds
dissolves in MeOH. The main part of the brominated compounds is strongly attached
to the skeletons but can be extracted for example by using Ba(OH)2. Various
halogenated tyrosine derivatives were identified by GC-MS and LC-MS in these
Ba(OH)2 extracts of the skeletons.
PMID- 25110919
TI - Structure elucidation of five novel isomeric saponins from the viscera of the sea
cucumber Holothuria lessoni.
AB - Sea cucumbers are prolific producers of a wide range of bioactive compounds. This
study aimed to purify and characterize one class of compound, the saponins, from
the viscera of the Australian sea cucumber Holothuria lessoni. The saponins were
obtained by ethanolic extraction of the viscera and enriched by a liquid-liquid
partition process and adsorption column chromatography. A high performance
centrifugal partition chromatography (HPCPC) was applied to the saponin-enriched
mixture to obtain saponins with high purity. The resultant purified saponins were
profiled using MALDI-MS/MS and ESI-MS/MS which revealed the structure of isomeric
saponins to contain multiple aglycones and/or sugar residues. We have elucidated
the structure of five novel saponins, Holothurins D/E and Holothurinosides X/Y/Z,
along with seven reported triterpene glycosides, including sulfated and non
sulfated saponins containing a range of aglycones and sugar moieties, from the
viscera of H. lessoni. The abundance of novel compounds from this species holds
promise for biotechnological applications.
PMID- 25110920
TI - Is apolipoprotein e required for cognitive function in humans?: implications for
Alzheimer drug development.
PMID- 25110921
TI - Antibacterial polymeric nanostructures for biomedical applications.
AB - The high incidence of bacterial infection and the growing resistance of bacteria
to conventional antibiotics have resulted in the strong need for the development
of new generation of antibiotics. Nano-sized particles have been considered as
novel antibacterial agents with high surface area and high reactivity. The
overall antibacterial properties of antimicrobial nanostructures can be
significantly enhanced compared with conventional antibacterial agents not in a
regular nanostructure, showing a better effect in inhibiting the growth and
reproduction of microbials such as bacteria and fungi, etc. In this review,
recent advances in the research and applications of antimicrobial polymeric
nanostructures have been highlighted, including silver-decorated polymer micelles
and vesicles, antimicrobial polymer micelles and vesicles, and antimicrobial
peptide-based vesicles, etc. Furthermore, we proposed the current challenges and
future research directions in the field of antibacterial polymeric nanostructures
for the real-world biomedical applications.
PMID- 25110922
TI - Early surgery and survival of patients with anaplastic thyroid carcinoma:
analysis of a case series referred to a single institution between 1999 and 2012.
AB - BACKGROUND: Extensive resection of the tumor has been associated with better
survival of anaplastic thyroid carcinoma (ATC) patients. However, surgery is not
the rule for ATC patients with distant metastases at the time of diagnosis (stage
IV-C), regardless of tumor resectability. The aim of this work was to explore the
potential role of surgery in ATC patients, including those in stage IV-C.
METHODS: We considered all the consecutive ATC patients referred to our
institution from June 1999 to July 2012. Patients with stage IV-A incidentally
discovered ATC were excluded because of their better prognosis. All patients
eligible for surgery at the time of diagnosis were first operated with the intent
to obtain a macroscopically complete resection (R0, R1), or a R2 resection with
minimal macroscopical residual tumor. These operations were defined as "maximal
debulking," whereas operations that did not achieve this goal were defined as
"partial debulking." After surgery, almost all patients received adjuvant
chemotherapy, associated to radiotherapy in more than 50% of patients. RESULTS:
There were 55 eligible patients (34 women; median age 73.15 years). Thirty-one
patients had distant metastases (stage IV-C). The median overall survival was
5.55 months [CI 4.94-6.60], with no difference according to stage. "Maximal
debulking" was obtained in 70.73% of operated patients as a first modality and
resulted associated with better survival than "partial debulking" (6.57 months
[CI 5.52-12.09] vs. 3.25 months [CI 0.66-4.80]), without any difference between
stage IV-B and IV-C patients. Furthermore, 21% of patients submitted to "maximal
debulking" died secondary to local progression of the tumor, whereas this was the
case for 69% of patients treated with "partial debulking" or not operated at all.
CONCLUSIONS: Early "maximal debulking," followed by adjuvant therapy, can improve
the survival and ameliorate the quality of residual life preventing the risk of
suffocation. This effect is also observed in patients with distant metastasis at
diagnosis and treated with this approach: they have an outcome similar to that
observed in stage IV-B patients. We thus suggest that surgery may be considered
in the management of all ATC patients, and should not be restricted a priori to
stages IV-A and IV-B.
PMID- 25110923
TI - Scope of physician procedures independently billed by mid-level providers in the
office setting.
AB - IMPORTANCE: Mid-level providers (nurse practitioners and physician assistants)
were originally envisioned to provide primary care services in underserved areas.
This study details the current scope of independent procedural billing to
Medicare of difficult, invasive, and surgical procedures by medical mid-level
providers. OBJECTIVE: To understand the scope of independent billing to Medicare
for procedures performed by mid-level providers in an outpatient office setting
for a calendar year. DESIGN: Analyses of the 2012 Medicare Physician/Supplier
Procedure Summary Master File, which reflects fee-for-service claims that were
paid by Medicare, for Current Procedural Terminology procedures independently
billed by mid-level providers. SETTING AND PARTICIPANTS: Outpatient office
setting among health care providers. MAIN OUTCOMES AND MEASURES: The scope of
independent billing to Medicare for procedures performed by mid-level providers.
RESULTS: In 2012, nurse practitioners and physician assistants billed
independently for more than 4 million procedures at our cutoff of 5000 paid
claims per procedure. Most (54.8%) of these procedures were performed in the
specialty area of dermatology. CONCLUSIONS AND RELEVANCE: The findings of this
study are relevant to safety and quality of care. Recently, the shortage of
primary care clinicians has prompted discussion of widening the scope of practice
for mid-level providers. It would be prudent to temper widening the scope of
practice of mid-level providers by recognizing that mid-level providers are not
solely limited to primary care, and may involve procedures for which they may not
have formal training.
PMID- 25110924
TI - Positive changes in self-management and disease severity following climate
therapy in people with psoriasis.
AB - The aim of this study was to investigate the impact of climate therapy on self
management in people with psoriasis. This was a prospective study of 254 adults
with chronic psoriasis who participated in a 3-week climate therapy (CT)
programme. The 8-scale Health Education Impact Questionnaire (heiQ) was completed
at baseline, after 3 weeks of CT, and 3 months later. Change was assessed using
paired sample t-tests mean (95% confidence interval) change scores (range 1-4).
All heiQ scales showed statistically significant improvement after 3 weeks of CT.
The greatest improvement was in Health-directed activity, followed by Emotional
distress, and Skill and technique acquisition. At the 3-month follow-up, only the
Emotional distress scale remained improved. In addition, disease severity (self
administered PASI; SAPASI) improved significantly from before CT to 3 weeks and 3
months after CT. This study suggests that CT provides a range of benefits that
are important to people with psoriasis, particularly in the short term. A
challenge is how to achieve long-term benefits.
PMID- 25110925
TI - Interfacial hydrogenation and deamination of nitriles to selectively synthesize
tertiary amines.
AB - A novel one-pot method has been developed for the interfacial hydrogenation of
nitriles to synthesize asymmetrical tertiary amines. The active Pt NWs allow for
the preparation of a series of tertiary amines in excellent yields (up to 99.0%)
and a mixed solvent is vital for the adjustment of the yield. And also, the
reaction proceeded under mild conditions and is environmentally friendly.
PMID- 25110926
TI - Looking for trouble -- patient preference, misdiagnosis and overtesting: a
teachable moment.
PMID- 25110927
TI - Rapid decline in HCV incidence among people who inject drugs associated with
national scale-up in coverage of a combination of harm reduction interventions.
AB - BACKGROUND: Government policy has precipitated recent changes in the provision of
harm reduction interventions - injecting equipment provision (IEP) and opiate
substitution therapy (OST) - for people who inject drugs (PWID) in Scotland. We
sought to examine the potential impact of these changes on hepatitis C virus
(HCV) transmission among PWID. METHODS AND FINDINGS: We used a framework to
triangulate different types of evidence: 'group-level/ecological' and 'individual
level'. Evidence was primarily generated from bio-behavioural cross-sectional
surveys of PWID, undertaken during 2008-2012. Individuals in the window period (1
2 months) where the virus is present, but antibodies have not yet been formed,
were considered to have recent infection. The survey data were supplemented with
service data on the provision of injecting equipment and OST. Ecological analyses
examined changes in intervention provision, self-reported intervention uptake,
self-reported risk behaviour and HCV incidence; individual-level analyses
investigated relationships within the pooled survey data. Nearly 8,000 PWID were
recruited in the surveys. We observed a decline in HCV incidence, per 100 person
years, from 13.6 (95% CI: 8.1-20.1) in 2008-09 to 7.3 (3.0-12.9) in 2011-12; a
period during which increases in the coverage of OST and IEP, and decreases in
the frequency of injecting and sharing of injecting equipment, were observed.
Individual-level evidence demonstrated that combined high coverage of
needles/syringes and OST were associated with reduced risk of recent HCV in
analyses that were unweighted (AOR 0.29, 95%CI 0.11-0.74) and weighted for
frequency of injecting (AORw 0.05, 95%CI 0.01-0.18). We estimate the combination
of harm reduction interventions may have averted 1400 new HCV infections during
2008-2012. CONCLUSIONS: This is the first study to demonstrate that impressive
reductions in HCV incidence can be achieved among PWID over a relatively short
time period through high coverage of a combination of interventions.
PMID- 25110929
TI - Influence of California-style black ripe olive processing on the formation of
acrylamide.
AB - Methods used in processing California-style black ripe olives generate
acrylamide. California-style black ripe olives contain higher levels of
acrylamide (409.67 +/- 42.60-511.91 +/- 34.08 MUg kg(-1)) as compared to
California-style green ripe olives (44.02 +/- 3.55-105.79 +/- 22.01 MUg kg(-1)),
Greek olives (<1.42 MUg kg(-1)), and Spanish olives (not detected), indicating
that the higher temperatures used to sterilize the California-style green ripe
and black ripe olives are required for acrylamide formation. Preprocessing brine
storage influenced the formation of acrylamide in a time-dependent manner.
Acrylamide increased during the first 30 days of storage. Longer brine storage
times (>30 days) result in lower acrylamide levels in the finished product. The
presence of calcium ions in the preprocessing brining solution results in higher
levels of acrylamide in finished products. Air oxidation during lye processing
and the neutralization of olives prior to sterilization significantly increase
the formation of acrylamide in the finished products. Conversely, lye-processing
decreases the levels of acrylamide in the final product. These results indicate
that specific steps in the California-style black ripe olive processing may be
manipulated to mitigate the formation of acrylamide in finished products.
PMID- 25110928
TI - Comparative analyses between retained introns and constitutively spliced introns
in Arabidopsis thaliana using random forest and support vector machine.
AB - One of the important modes of pre-mRNA post-transcriptional modification is
alternative splicing. Alternative splicing allows creation of many distinct
mature mRNA transcripts from a single gene by utilizing different splice sites.
In plants like Arabidopsis thaliana, the most common type of alternative splicing
is intron retention. Many studies in the past focus on positional distribution of
retained introns (RIs) among different genic regions and their expression
regulations, while little systematic classification of RIs from constitutively
spliced introns (CSIs) has been conducted using machine learning approaches. We
used random forest and support vector machine (SVM) with radial basis kernel
function (RBF) to differentiate these two types of introns in Arabidopsis. By
comparing coordinates of introns of all annotated mRNAs from TAIR10, we obtained
our high-quality experimental data. To distinguish RIs from CSIs, We investigated
the unique characteristics of RIs in comparison with CSIs and finally extracted
37 quantitative features: local and global nucleotide sequence features of
introns, frequent motifs, the signal strength of splice sites, and the similarity
between sequences of introns and their flanking regions. We demonstrated that our
proposed feature extraction approach was more accurate in effectively classifying
RIs from CSIs in comparison with other four approaches. The optimal penalty
parameter C and the RBF kernel parameter [Formula: see text] in SVM were set
based on particle swarm optimization algorithm (PSOSVM). Our classification
performance showed F-Measure of 80.8% (random forest) and 77.4% (PSOSVM). Not
only the basic sequence features and positional distribution characteristics of
RIs were obtained, but also putative regulatory motifs in intron splicing were
predicted based on our feature extraction approach. Clearly, our study will
facilitate a better understanding of underlying mechanisms involved in intron
retention.
PMID- 25110930
TI - Efficacy and safety of adding clopidogrel to aspirin on stroke prevention among
high vascular risk patients: a meta-analysis of randomized controlled trials.
AB - OBJECTIVES: Whether clopidogrel should be added to aspirin for stroke prevention
remained controversial for the risk of hemorrhagic complications. This meta
analysis was aimed to assess the efficacy and safety of adding clopidogrel to
aspirin on stroke prevention in high vascular risk patients, and to provide
evidence for a suitable duration of dual antiplatelet therapy. METHODS: We
searched PubMed, EMBase, OVID and Cochrane Central Register of Controlled Trials
(up to June, 2013) for randomized controlled trials evaluating the efficacy and
safety of clopidogrel plus aspirin versus aspirin alone in high vascular risk
patients. Comparisons of stroke and hemorrhagic complications between treatment
groups were expressed by the pooled Relative Risks (RRs) with 95% Confidence
Intervals (CIs). RESULTS: Fifteen trials with a total of 97692 intention-to-treat
participants were included with duration of follow-up ranging from 7 days to 3.6
years. Dual antiplatelet therapy reduced all stroke by 21% (RR: 0.79, 95% CI:
0.73-0.85) with no evidence of heterogeneity across the trials (P = 0.27, I2 =
17%).The effects were consistent between short-term subgroup (<=1 month, RR:
0.76, 95% CI: 0.67-0.85) and long-term subgroup (>=3 months, RR: 0.81, 95% CI:
0.73-0.89). The risk of major bleeding was not significantly increased by dual
antiplatelet therapy in short-term subgroup (RR: 1.11, 95% CI: 0.91-1.36), while
significantly increased in long-term subgroup (RR: 1.52, 95% CI: 1.36-1.69). Long
term dual antiplatelet therapy substantially increased the risk of intracranial
bleeding (RR: 1.76, 95% CI: 1.22-2.54). CONCLUSIONS: This meta-analysis
demonstrates that short-term combination of clopidogrel and aspirin is effective
and safe for stroke prevention in high vascular risk patients. Long-term
combination therapy substantially increases the risk of major bleeding and
intracranial bleeding.
PMID- 25110931
TI - Cognitive deficits predict poorer functional capacity in Huntington's disease:
but what is being measured?
AB - OBJECTIVE: Huntington's disease (HD) is an inherited movement disorder
characterized by choreiform movements and frontostriatal dysfunction. Previous
studies have documented executive deficits in HD. We aimed to investigate the
effect of cognitive deficits on patients' daily functioning. Furthermore, we
sought to explore how independent patients' cognitive difficulties were from
their motor and psychiatric symptoms. METHOD: We administered a battery of
neuropsychological tasks assessing broader cognitive abilities and executive
functions (e.g., verbal fluency, working memory, response inhibition) to 25
patients with HD and 20 healthy controls. Clinical ratings of functional capacity
and the severity of motor and psychiatric symptoms were also taken. After
establishing that patients with HD demonstrated characteristic cognitive
deficits, we explored relationships between performance on neuropsychological
tasks and clinical ratings. RESULTS: Patients with HD exhibited deficits on all
timed neuropsychological tasks but not on measures of accuracy. Poorer functional
capacity was related to cognitive deficits and more severe motor symptoms. Motor
and psychiatric symptoms were also related to cognitive performance. Category
fluency scores alone predicted 54% of the variance in functional capacity.
CONCLUSIONS: Patients with HD exhibited a pattern of cognitive dysfunction that
may reflect a generalized slowing in processing. It is important to note that we
found that certain cognitive measures may help predict functional capacity in HD.
However, we also highlight that performance on neuropsychological tasks can be
influenced by motor or psychiatric symptoms. Future studies should consider such
confounds when seeking purer measures of cognitive capacity.
PMID- 25110932
TI - The role of the occipital face area in holistic processing involved in face
detection and discrimination: A tDCS study.
AB - OBJECTIVE: The aim of this study was to examine the role of occipital face area
(OFA) in mediating observers' tendency to perceive faces as "wholes" (holistic
processing) both when detecting and discriminating faces. To investigate this
issue, we modulated OFA activity using transcranial direct current stimulation
(tDCS). METHOD: In Experiment 1, participants performed a face detection task
(the Mooney faces task) and a face discrimination task (the Composite faces
task), which both assess holistic face processing. In Experiment 2, participants
were asked to detect both Mooney faces and Mooney objects, to test face
selectivity of OFA. In each experimental session, the tasks were presented once
before (pre) and once after (post) administration of 20 min of excitability
increasing anodal tDCS (real) and sham stimulation over the putative OFA.
RESULTS: Compared with sham stimulation, we found that real anodal tDCS
interfered with both Mooney faces and objects detection, whereas it had no effect
on holistic processing involved in face discrimination, as measured by the
Composite faces task. CONCLUSIONS: Our results suggest that OFA is causally
implicated in facial detection at least in degraded conditions (i.e., when the
"face" signal needs to be extracted from a noisy background). In turn, our data
do not implicate OFA in holistic processing in face discrimination. Finally, our
data suggest a possible role of OFA in categorization of other nonface stimuli, a
conclusion that must be taken with caution, as stimulation over OFA may affect
object-selective adjacent regions.
PMID- 25110935
TI - Recent advances in Charcot-Marie-Tooth disease.
AB - PURPOSE OF REVIEW: This article focuses on recent advances in Charcot-Marie-Tooth
disease, in particular additions to the genetic spectrum, novel paradigms in
molecular techniques and an update on therapeutic strategies. RECENT FINDINGS:
Several new Charcot-Marie-Tooth disease-causing genes have been recently
identified, further enlarging the genetic diversity and phenotypic variability,
including: SBF1, DHTKD1, TFG, MARS, HARS, HINT1, TRIM1, AIFM1, PDK3 and GNB4. The
increasing availability and affordability of next-generation sequencing
technologies has ramped up gene discovery and drastically changed genetic
screening strategies. All large-scale trials studying the effect of ascorbic acid
in Charcot-Marie-Tooth 1A have now been completed and were negative. Efforts have
been made to design more robust outcome-measures for clinical trials. Promising
results with lonaprisan, curcumin and histone deacetylase 6 inhibitors have been
obtained in animal models. SUMMARY: Charcot-Marie-Tooth is the most common form
of inherited peripheral neuropathy and represents the most prevalent hereditary
neuromuscular disorder. The genetic spectrum spans more than 70 genes. Gene
discovery has been revolutionized recently by new high-throughput molecular
technologies. In addition, the phenotypic diversity has grown tremendously. This
is a major challenge for geneticists and neurologists. No effective therapy is
available for Charcot-Marie-Tooth. Several large trials with ascorbic acid were
negative but research into novel compounds continues.
PMID- 25110934
TI - The evidence for symptomatic treatments in amyotrophic lateral sclerosis.
AB - PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) is a progressive,
incurable and fatal neurodegenerative disease. Few interventions significantly
alter the disease course, but many symptomatic treatments exist to improve
patients' quality of life. In this review, we describe our approach to
symptomatic management of ALS and discuss the underlying evidence base. RECENT
FINDINGS: Discussion focuses predominantly on recently published articles. We
cover management settings, disease-modifying treatment, vitamin D, respiratory
management including noninvasive ventilation and diaphragmatic pacing,
secretions, nutrition, dysphagia and gastrostomy, communication problems,
mobility, spasticity, pain, cognition, depression and emotional lability,
fatigue, sleep disturbance, head drop, prevention of deep venous thrombosis and
end-of-life issues. SUMMARY: Multidisciplinary specialist care appears to improve
quality of life and survival. Riluzole remains the only available disease
modifying medication and confers a survival advantage of 2-3 months. Noninvasive
ventilation improves quality of life and extends survival by approximately 7
months, at least in patients without severe bulbar problems. Nutrition is an
independent prognostic factor; whether gastrostomy improves survival and quality
of life remains unclear and further studies are underway. Many other symptomatic
treatments appear helpful to individuals in clinic, but further randomized
clinical trials are required to provide a more robust evidence base.
PMID- 25110933
TI - Early life instruction in foreign language and music and incidence of mild
cognitive impairment.
AB - OBJECTIVE: To test the hypothesis that foreign language and music instruction in
early life are associated with lower incidence of mild cognitive impairment (MCI)
and slower rate of cognitive decline in old age. METHOD: At enrollment in a
longitudinal cohort study, 964 older persons without cognitive impairment
estimated years of foreign language and music instruction by age 18. Annually
thereafter they completed clinical evaluations that included cognitive testing
and clinical classification of MCI. RESULTS: There were 264 persons with no
foreign language instruction, 576 with 1-4 years, and 124 with > 4 years; 346
persons with no music instruction, 360 with 1-4 years, and 258 with > 4 years.
During a mean of 5.8 years of observation, 396 participants (41.1%) developed
MCI. In a proportional hazards model adjusted for age, sex, and education, higher
levels (> 4 years) of foreign language (hazard ratio [HR] = 0.687, 95% confidence
interval [CI] [0.482, 0.961]) and music (HR = 0.708, 95% CI [0.539, 0.930])
instruction by the age of 18 were each associated with reduced risk of MCI. The
association persisted after adjustment for other early life indicators of an
enriched cognitive environment, and it was stronger for nonamnestic than amnestic
MCI. Both foreign language and music instruction were associated with higher
initial level of cognitive function, but neither instruction measure was
associated with cognitive decline. CONCLUSIONS: Higher levels of foreign language
and music instruction during childhood and adolescence are associated in old age
with lower risk of developing MCI but not with rate of cognitive decline.
PMID- 25110936
TI - The Effect of a Community-Engaged Arts Program on Older Adults' Well-being.
AB - This mixed-methods study evaluated the effect of a community-engaged arts program
on the physical, emotional, and social well-being of seniors. Weekly workshops
were offered over a three-year period at community centers where artists worked
with four groups of seniors to produce a collective art piece or performance for
public presentation. Participants completed pre- and post- questionnaires, and
group interviews were conducted at the program's end. Paired t-test analyses
indicated that seniors experienced improvement in perceived overall health,
experience of pain, and sense of community. Interpretive descriptive analysis of
the group interviews revealed six themes that informed understanding : (1)
providing structure and discipline; (2) facilitating coping; (3) requiring hard
work and effort; (4) bringing out one's artistic side; (5) promoting social
involvement; and (6) making a contribution. These results are consistent with
previous research and contribute to further understanding of how community
engaged arts can benefit the well-being of older people.
PMID- 25110937
TI - Engineering efficient thermoelectrics from large-scale assemblies of doped ZnO
nanowires: nanoscale effects and resonant-level scattering.
AB - Recent studies focusing on enhancing the thermoelectric performance of metal
oxides were primarily motivated by their low cost, large availability of the
component elements in the earth's crust, and their high stability. So far, these
studies indicate that n-type materials, such as ZnO, have much lower
thermoelectric performance than their p-type counterparts. Overcoming this
limitation requires precisely tuning the thermal and electrical transport through
n-type metal oxides. One way to accomplish this is through the use of optimally
doped bulk assemblies of ZnO nanowires. In this study, the thermoelectric
properties of n-type aluminum and gallium dually doped bulk assembles of ZnO
nanowires were determined. The results indicated that a high zT of 0.6 at 1000
degrees C, the highest experimentally observed for any n-type oxide, is possible.
The high performance is attributed to the tailoring of the ZnO phase composition,
nanostructuring of the material, and Zn-III band hybridization-based resonant
scattering.
PMID- 25110938
TI - A comprehensive global inventory of atmospheric Antimony emissions from
anthropogenic activities, 1995-2010.
AB - Antimony (Sb) and its compounds are considered as global pollutants due to their
health risks and long-range transport characteristics. A comprehensive global
inventory of atmospheric antimony emissions from anthropogenic activities during
the period of 1995-2010 has been developed with specific estimation methods based
on the relevant data available for different continents and countries. Our
results indicate that the global antimony emissions have increased to a peak at
about 2232 t (t) in 2005 and then declined gradually. Global antimony emissions
in 2010 are estimated at about 1904 t (uncertainty of a 95% confidence interval
(CI): -30% ~ 67%), with fuel combustion as the major source category. Asia and
Europe account for about 57% and 24%, respectively, of the global total
emissions, and China, the United States, and Japan rank as the top three emitting
countries. Furthermore, global antimony emissions are distributed into gridded
cells with a resolution of 1 degrees * 1 degrees . Regions with high Sb
emissions are generally concentrated in the Southeastern Asia and Western Europe,
while South Africa, economically developed regions in the eastern U.S., and
Mexico are also responsible for the high antimony emission intensity.
PMID- 25110940
TI - Solving the problem of comparing whole bacterial genomes across different
sequencing platforms.
AB - Whole genome sequencing (WGS) shows great potential for real-time monitoring and
identification of infectious disease outbreaks. However, rapid and reliable
comparison of data generated in multiple laboratories and using multiple
technologies is essential. So far studies have focused on using one technology
because each technology has a systematic bias making integration of data
generated from different platforms difficult. We developed two different
procedures for identifying variable sites and inferring phylogenies in WGS data
across multiple platforms. The methods were evaluated on three bacterial data
sets and sequenced on three different platforms (Illumina, 454, Ion Torrent). We
show that the methods are able to overcome the systematic biases caused by the
sequencers and infer the expected phylogenies. It is concluded that the cause of
the success of these new procedures is due to a validation of all informative
sites that are included in the analysis. The procedures are available as web
tools.
PMID- 25110941
TI - Laccase biosensor based on phytic acid modification of nanostructured SiO2
surface for sensitive detection of dopamine.
AB - In this work, three kinds of nanostructured silica-phytic acid (SiO2-PA)
materials with diverse morphologies including spherical SiO2-PA (s-SiO2-PA), rod
like (r-SiO2-PA), and helical SiO2-PA (h-SiO2-PA) were prepared with the help of
electrostatic interaction. The SiO2-PA nanomaterials with different morphologies
were characterized by using transmission electron microscopy (TEM), Fourier
transform infrared (FTIR), electrochemical impedance spectroscopy (EIS), and
circular dichroism spectrum (CD). Diverse morphologies of SiO2-PA were used as
electrode decorated materials to achieve a high efficiency for electrochemical
dopamine (DA) detection. The laccase biosensors were fabricated by immobilizing
different morphologies of SiO2-PA nanomaterials and laccase onto the glassy
carbon electrode (GCE) surface, successively. Then the electrochemical responses
of the different morphologies of nanostructured SiO2-PA nanomaterials to laccase
were discussed. Results indicated that compared to laccase/s-SiO2-PA and
laccase/r-SiO2-PA, the laccase/h-SiO2-PA-modified electrode showed the best
electrochemical performances.
PMID- 25110942
TI - Relativistic and electron-correlation effects on the nuclear magnetic resonance
shieldings of molecules containing tin and lead atoms.
AB - The reference values for NMR magnetic shieldings, sigma(ref), are of the highest
importance when theoretical analysis of chemical shifts are envisaged. The fact
that the nonrelativistically valid relationship among spin-rotation constants and
magnetic shieldings is not any longer valid for heavy atoms requires that the
search for sigma(ref) for such atoms needs new strategies to follow. We present
here results of sigma(ref) that were obtained by applying our own simple
procedure which mixes accurate experimental chemical shifts (delta) and
theoretical magnetic shieldings (sigma). We calculated sigma(Sn) and sigma(Pb) in
a family of heavy-halogen-containing molecules. We found out that
sigma(ref)[Sn;Sn(CH3)4] in gas phase should be close to 3864.11 +/- 20.05 ppm
(0.5%). For Pb atom, sigma(ref)[Pb;Pb(CH3)4] should be close to 14475.1 +/- 500.7
ppm. Such theoretical values correspond to calculations with the relativistic
polarization propagator method, RelPPA, at the RPA level of approach. They are
closer to experimental values as compared to those obtained applying few
different functionals such as PBE0, B3LYP, BLYP, BP86, KT2, and KT3 of the
density functional theory, DFT. We studied tin and lead shieldings of the XY(4
n)Z(n) (X = Sn, Pb; Y, Z = H, F, Cl, Br, I) and PbH(4-n)I(n) (n = 0, 1, 2, 3, 4)
family of compounds with four-component functionals as implemented in the DIRAC
code. For these systems results of calculations with RelPPA-RPA are more reliable
than DFT ones. We argue about why those DFT functionals must be modified in order
to obtain more accurate results of NMR magnetic shieldings within the
relativistic regime: first, there is a dependence among both electron-correlation
and relativistic effects that should be introduced in some way in the
functionals; and second, the DIRAC code uses standard nonrelativistic functionals
and the functionals B3LYP and PBE0 were parametrized only with data taken from
light elements. It can explain why they are not able to properly introduce
relativistic effects on nuclear magnetic shieldings. We finally show that in the
analysis of magnetic shieldings for the family of compounds mentioned above, one
must consider the newest and so-called heavy-atom effect on vicinal heavy atoms,
HAVHA. Such effects are among the most important relativistic effects in these
kind of compounds.
PMID- 25110943
TI - Synthesis of pyrrolo-/indolo[1,2-a]quinolines and naphtho[2,1-b]thiophenes from
gem-dibromovinyls and sulphonamides.
AB - A highly efficient and simple route for the synthesis of pyrrolo-/indolo[1,2
a]quinolines and naphtho[2,1-b]thiophenes from gem-dibromovinyls and
sulphonamides is reported. The noteworthy feature of this report is that the
methodology involves a two-step protocol to synthesize tri- and tetracyclic
heterocycles in a one-pot fashion through the Cu(I)-catalyzed formation of
ynamide followed by a Ag(I)-assisted intramolecular hydroarylation. The
photophysical properties of representative examples of pyrrolo- and indolo[1,2
a]quinolines in solid and solution states have also been studied.
PMID- 25110944
TI - Parametrization of 2,2,2-trifluoroethanol based on the generalized AMBER force
field provides realistic agreement between experimental and calculated properties
of pure liquid as well as water-mixed solutions.
AB - We present a novel force field model of 2,2,2-trifluoroethanol (TFE) based on the
generalized AMBER force field. The model was exhaustively parametrized to
reproduce liquid-state properties of pure TFE, namely, density, enthalpy of
vaporization, self-diffusion coefficient, and population of trans and gauche
conformers. The model predicts excellently other liquid-state properties such as
shear viscosity, thermal expansion coefficient, and isotropic compressibility.
The resulting model describes unexpectedly well the state equation of the liquid
region in the range of 100 K and 10 MPa. More importantly, the proposed TFE model
was optimized for use in combination with the TIP4P/Ew and TIP4P/2005 water
models. It does not manifest excessive aggregation, which is known for other
models, and therefore, it is supposed to more realistically describe the behavior
of TFE/water mixtures. This was demonstrated by means of the Kirkwood-Buff theory
of solutions and reasonable agreement with experimental data. We explored a
considerable part of the parameter space and systematically tested individual
combinations of parameters for performance in combination with the TIP4P/Ew and
TIP4P/2005 water models. We observed ambiguity in parameters describing pure
liquid TFE; however, most of them failed for TFE/water mixtures. We clearly
demonstrated the necessity for balanced TFE-TFE, TFE-water, and water-water
interactions which can be acquired only by employing implicit polarization
correction in the course of parametrization.
PMID- 25110946
TI - Catalytic hydrogen evolution by Fe(II) carbonyls featuring a dithiolate and a
chelating phosphine.
AB - Two pentacoordinate mononuclear iron carbonyls of the form (bdt)Fe(CO)P2 [bdt =
benzene-1,2-dithiolate; P2 = 1,1'-diphenylphosphinoferrocene (1) or methyl-2
{bis(diphenylphosphinomethyl)amino}acetate (2)] were prepared as functional,
biomimetic models for the distal iron (Fe(d)) of the active site of [FeFe]
hydrogenase. X-ray crystal structures of the complexes reveal that, despite
similar nu(CO) stretching band frequencies, the two complexes have different
coordination geometries. In X-ray crystal structures, the iron center of 1 is in
a distorted trigonal bipyramidal arrangement, and that of 2 is in a distorted
square pyramidal geometry. Electrochemical investigation shows that both
complexes catalyze electrochemical proton reduction from acetic acid at mild
overpotential, 0.17 and 0.38 V for 1 and 2, respectively. Although coordinatively
unsaturated, the complexes display only weak, reversible binding affinity toward
CO (1 bar). However, ligand centered protonation by the strong acid, HBF4.OEt2,
triggers quantitative CO uptake by 1 to form a dicarbonyl analogue [1(H)-CO](+)
that can be reversibly converted back to 1 by deprotonation using NEt3. Both
crystallographically determined distances within the bdt ligand and density
functional theory calculations suggest that the iron centers in both 1 and 2 are
partially reduced at the expense of partial oxidation of the bdt ligand. Ligand
protonation interrupts this extensive electronic delocalization between the Fe
and bdt making 1(H)(+) susceptible to external CO binding.
PMID- 25110947
TI - Clearance of intravitreal daptomycin in uveitis-induced rabbit model.
AB - PURPOSE: To investigate the elimination rate of daptomycin after intravitreal
injection in uveitis-induced rabbits. MATERIALS AND METHODS: Intravitreal
injection of the single dose of 200 MUg/0.05 mL daptomycin was administered to
rabbits starting 24 h after induction of uveitis by an intravitreal endotoxin
injection. Aqueous humor and vitreous humor samples of eight eyes per time point
were collected at selected time intervals (1, 3, 6, 24, 48, 72 and 96 h), and the
in vitreous half-life was calculated. Daptomycin concentrations in vitreous and
aqueous humor were assayed with high-performance liquid chromatography. RESULTS:
The vitreous concentration was noted to decline slowly with time. The mean
vitreous concentration was 23.25 +/- 10.99 MUg/mL and 11.10 +/- 3.33 MUg/mL at 96
h in inflamed and normal eyes, respectively. The vitreous daptomycin
concentration showed an exponential decay with a half-life of 25.67 h in normal
eyes and 34.6 h in inflamed eyes. The aqueous levels of daptomycin in normal eyes
were low but remained significantly higher than those of inflamed eyes.
CONCLUSIONS: Given that the injected dose corresponds to several times the
minimum inhibitory concentrations of organisms most involved in endophthalmitis,
and that therapeutic levels are present up to 96 h after injection, intravitreal
daptomycin should be considered for the treatment of endophthalmitis caused by
Gram-positive bacteria.
PMID- 25110948
TI - Antibiotic susceptibilities of bacteria isolated within the oral flora of Florida
blacktip sharks: guidance for empiric antibiotic therapy.
AB - Sharks possess a variety of pathogenic bacteria in their oral cavity that may
potentially be transferred into humans during a bite. The aim of the presented
study focused on the identification of the bacteria present in the mouths of live
blacktip sharks, Carcharhinus limbatus, and the extent that these bacteria
possess multi-drug resistance. Swabs were taken from the oral cavity of nineteen
live blacktip sharks, which were subsequently released. The average fork length
was 146 cm (+/-11), suggesting the blacktip sharks were mature adults at least 8
years old. All swabs underwent standard microbiological work-up with
identification of organisms and reporting of antibiotic susceptibilities using an
automated microbiology system. The oral samples revealed an average of 2.72 (+/
1.4) bacterial isolates per shark. Gram-negative bacteria, making up 61% of all
bacterial isolates, were significantly (p<0.001) more common than gram-positive
bacteria (39%). The most common organisms were Vibrio spp. (28%), various
coagulase-negative Staphylococcus spp. (16%), and Pasteurella spp. (12%). The
overall resistance rate was 12% for all antibiotics tested with nearly 43% of
bacteria resistant to at least one antibiotic. Multi-drug resistance was seen in
4% of bacteria. No association between shark gender or fork length with bacterial
density or antibiotic resistance was observed. Antibiotics with the highest
overall susceptibility rates included fluoroquinolones, 3rd generation
cephalosporins and sulfamethoxazole/trimethoprim. Recommended empiric
antimicrobial therapy for adult blacktip shark bites should encompass either a
fluoroquinolone or combination of a 3rd generation cephalosporin plus
doxycycline.
PMID- 25110949
TI - Anti-human herpesvirus 6A/B IgG correlates with relapses and progression in
multiple sclerosis.
AB - OBJECTIVE: To analyze the titers of the IgG and IgM antibodies against human
herpesvirus 6A/B (HHV-6A/B) in multiple sclerosis (MS) patients treated with
different disease modified therapies (DMTs) along two-years of follow-up.
METHODS: We collected 2163 serum samples from 596 MS; for 301 MS patients a 2
years follow-up was performed. Serum samples of 337 healthy controls were also
analyzed. Anti-HHV-6A/B IgG and IgM were analyzed by ELISA (Panbio). RESULTS: We
found that 129/187 (69.0%) MS patients with a decrease of the anti-HHV-6A/B IgG
titers after 2-years with DMTs were free of relapses and progression vs. 46/113
(40.7%) of MS patients with an increase of the anti-HHV-6A/B IgG titers (p =
0.0000015); the higher significance was found for natalizumab. Furthermore, we
found that anti-HHV-6A/B IgG titers reached their highest value two weeks before
the relapse (p = 0.0142), while the anti-HHV-6A/B IgM titers reached their
highest value one month before the relapse (p = 0.0344). CONCLUSION: The
measurement of the anti-HHV-6A/B IgG titers could be a good biomarker of clinical
response to the different DMTs. The increase of the anti-HHV-6A/B IgG and IgM
titers predicts the upcoming clinical relapses. However, further longitudinal
studies are needed to validate these results.
PMID- 25110951
TI - In silico modeling of human alpha2C-adrenoreceptor interaction with filamin-2.
AB - Vascular smooth muscle alpha2C-adrenoceptors (alpha2C-ARs) mediate
vasoconstriction of small blood vessels, especially arterioles. Studies of
endogenous receptors in human arteriolar smooth muscle cells (referred to as
microVSM) and transiently transfected receptors in heterologous HEK293 cells show
that the alpha2C-ARs are perinuclear receptors that translocate to the cell
surface under cellular stress and elicit a biological response. Recent studies in
microVSM unraveled a crucial role of Rap1A-Rho-ROCK-F-actin pathways in receptor
translocation, and identified protein-protein interaction of alpha2C-ARs with the
actin binding protein filamin-2 as an essential step in the process. To better
understand the molecular nature and specificity of this interaction, in this
study, we constructed comparative models of human alpha2C-AR and human filamin-2
proteins. Finally, we performed in silico protein-protein docking to provide a
structural platform for the investigation of human alpha2C-AR and filamin-2
interactions. We found that electrostatic interactions seem to play a key role in
this complex formation which manifests in interactions between the C-terminal
arginines of alpha2C-ARs (particularly R454 and R456) and negatively charged
residues from filamin-2 region between residues 1979 and 2206. Phylogenetic and
sequence analysis showed that these interactions have evolved in warm-blooded
animals.
PMID- 25110952
TI - The effect of double--blind carbohydrate ingestion during 60 km of self-paced
exercise in warm ambient conditions.
AB - This study evaluated double blind ingestions of placebo (PLA) versus 6%
carbohydrate (CHO) either as capsules (c) or beverage (b) during 60 km self-paced
cycling in the heat (32 degrees C and 50% relative humidity). Ten well-trained
males (mean +/- SD: 26+/-3 years; 64.5+/-7.7 kg and 70.7+/-8.8 ml.kg-1.min-1
maximal oxygen consumption) completed four separate 60 km time trials (TT)
punctuated by 1 km sprints (14, 29, 44, 59 km) whilst ingesting either PLAb or
PLAc or CHOb or CHOc. The TT was not different among treatments (PLAb 130.2+/
11.2 min, CHOb 140.5+/-18.1 min, PLAc 143.1+/-29.2 min, CHOc 137.3+/-20.1 min;
P>0.05). Effect size (Cohen's d) for time was only moderate when comparing CHOb -
PLAb (d = 0.68) and PLAb - PLAc (d = 0.57) whereas all other ES were 'trivial' to
'small'. Mean speed throughout the trial was significantly higher for PLAb only
(P<0.05). Power output was only different (P<0.05) between the sprints and low
intensity efforts within and across conditions. Core and mean skin temperatures
were similar among trials. We conclude that CHO ingestion is of little or no
benefit as a beverage compared with placebo during 60 km TT in the heat.
PMID- 25110953
TI - Inhibition of CSF-1R supports T-cell mediated melanoma therapy.
AB - Tumor associated macrophages (TAM) can promote angiogenesis, invasiveness and
immunosuppression. The cytokine CSF-1 (or M-CSF) is an important factor of TAM
recruitment and differentiation and several pharmacological agents targeting the
CSF-1 receptor (CSF-1R) have been developed to regulate TAM in solid cancers. We
show that the kinase inhibitor PLX3397 strongly dampened the systemic and local
accumulation of macrophages driven by B16F10 melanomas, without affecting Gr-1(+)
myeloid derived suppressor cells. Removal of intratumoral macrophages was
remarkably efficient and a modest, but statistically significant, delay in
melanoma outgrowth was observed. Importantly, CSF-1R inhibition strongly enhanced
tumor control by immunotherapy using tumor-specific CD8 T cells. Elevated
IFNgamma production by T cells was observed in mice treated with the combination
of PLX3397 and immunotherapy. These results support the combined use of CSF-1R
inhibition with CD8 T cell immunotherapy, especially for macrophage-stimulating
tumors.
PMID- 25110954
TI - Reflections on clinical expertise and silent know-how in voice therapy.
AB - The concept of 'clinical expertise' is described as a part of evidence-based
practice (EBP) together with 'external scientific evidence' and 'patient values
and perspectives'. However, clinical expertise in the management of voice
disorders has not been described or discussed in much detail. The expertise seems
to consist partly of silent know-how that, from the outside, may seem improperly
related to the personality of the speech-language pathologist or exclusively
dependent on the number of years in the field. In this paper, it is suggested
that clinical expertise in voice therapy consists of specific skills that can be
explicitly described and trained. These skills are discussed together with
educational aspects that contribute to the development of clinical expertise. The
skills are also discussed from the perspectives of the past, present, and future.
PMID- 25110955
TI - Unilateral full-thickness macular hole formation following low-energy Nd:YAG
peripheral iridotomy.
AB - Macular hole formation is a rare complication after YAG peripheral iridotomy. We
report a case of post-YAG peripheral iridotomy macular hole in 1 eye of a patient
with preexisting vitreomacular adhesion in that eye. Possibly because of the
vitreomacular adhesion, a single-shot low-energy YAG laser shot resulted in
macular hole formation.
PMID- 25110956
TI - Amniotic membrane transplantation in failed trabeculectomy.
AB - PURPOSE: To determine the efficacy and safety of amniotic membrane
transplantation for trabeculectomy in patients with previous failed filtering
blebs. METHODS: A consecutive series of 19 eyes from 18 patients with 1 or more
failed trabeculectomies were enrolled in this retrospective study.
Trabeculectomy, with amniotic membrane positioned as a "graft" under the scleral
flap, was performed, and the intraocular pressure (IOP), number of antiglaucoma
medications, appearance of the filtering bleb, and intraoperative and
postoperative complication data were retrospectively analyzed for a period of 24
months. Success was defined as IOP<21 mm Hg at the end of the follow-up period.
RESULTS: The median preoperative pressure was 29 mm Hg [interquartile range
(IQR)=5 mm Hg], with an average of 2.8 glaucoma medications (range, 1 to 4). At 6
months postoperatively the median IOP was 18 mm Hg (IQR=1.75 mm Hg) with no
further significant increases recorded, settling at 19 mm Hg (IQR=3.25 mm Hg) at
the end of the 24-month follow-up. Success was achieved in all 19 cases (100%),
and only 1 patient (5%) required postoperative antiglaucoma therapy to reach the
target pressure. At 24 months after surgery, 18 of 19 (95%) amniotic membrane
filtering blebs were functioning well without antiglaucoma therapy. No patients
had severe intraoperative or postoperative complications. CONCLUSIONS: Amniotic
membrane transplantation in trabeculectomy seems to be a safe and useful
procedure for improving the surgical outcome and maintaining low postoperative
IOP in patients with a high risk of surgical failure.
PMID- 25110957
TI - A computational study of the activation of allenoates by Lewis bases and the
reactivity of intermediate adducts.
AB - Several chemical properties of Lewis base-allenoate adducts (LB.allenoate), such
as solvent effect, basicity, nucleophilicity and cycloaddition, are studied to
provide a detailed foundation for the analysis of LB-catalyzed reactions of
allenoates. The zwitterionic LB.allenoates formed between methyl allenoate and
Lewis bases, such as N-heterocyclic carbenes (NHCs), phosphines, amines and aza
heterocycles, are studied at the M06-2X/6-31+G* level. The addition of the LBs to
the allenoate can yield Z- or E-type adducts. The formation of the Z-type adducts
is more favorable in the gas phase due to electrostatic interactions. The yield
of the E-type adducts increases with the permittivity of the solvent. The lowest
barriers for the addition and the most stable adducts are observed with NHCs as
catalysts. It is also shown that the alpha-carbon atom of the allenic moiety in
LB.allenoate is more nucleophilic than the gamma-carbon atom. Aza-arenes,
phosphines and NHCs stabilize the [3 + 2]-ylides formed by the cycloaddition of
LB.allenoate to ethylene; therefore, these LBs thermodynamically support the [3 +
2] cycloadditions. The detailed analysis of [3 + 2]-, [2 + 4]-, [2 + 2]- and [2 +
2 + 2]-cycloadditions with enones/ketones shows that the amine-catalyzed
reactions follow the kinetically preferred path, and that the exergonic formation
of the P-ylide favors the [3 + 2] cycloaddition in the phosphine-catalyzed
reaction. The thermodynamically preferred pathway is followed with NHCs whereas
the high stability of NHC.allenoate adducts reduces the overall catalytic
efficiency of NHCs.
PMID- 25110959
TI - Theoretical and experimental investigations of the potential of osmotic energy
for power production.
AB - This paper presents a study on the potential of osmotic energy for power
production. The study includes both pilot plant testing and theoretical modelling
as well as cost estimation. A projected cost of L30/MWh of clean electricity
could be achieved by using a Hydro-Osmotic Power (HOP) plant if a suitable
membrane is used and the osmotic potential difference between the two solutions
is greater than 25 bar; a condition that can be readily found in many sites
around the world. Results have shown that the membrane system accounts for 50%
80% of the HOP plant cost depending on the salinity difference level. Thus,
further development in membrane technology and identifying suitable membranes
would have a significant impact on the feasibility of the process and the route
to market. As the membrane permeability determines the HOP process feasibility,
this paper also describes the effect of the interaction between the fluid and the
membrane on the system permeability. It has been shown that both the fluid
physical properties as well as the membrane micro-structural parameters need to
be considered if further development of the HOP process is to be achieved.
PMID- 25110958
TI - Sex-Related Alcohol Expectancies Among African American Women Attending an Urban
STI Clinic.
AB - African American women are disproportionately affected by human immunodeficiency
virus/acquired immunodeficiency syndrome (HIV/AIDS) and sexually transmitted
infections (STIs). Alcohol use is a significant risk factor for HIV/STI
acquisition. Sex-related alcohol expectancies (SRAEs) may partially account for
alcohol-related risky sexual behaviors. Using qualitative interviews we explored
the link between alcohol use and risky sex among 20 African American women
attending an STI clinic who had consumed four or more alcoholic drinks per
drinking day (binge drinking) and/or reported vaginal or anal sex while under the
influence of alcohol. Four SRAEs emerged, which we named drink for sexual desire,
drink for sexual power, drink for sexual excuse, and drink for anal sex. While
the desire SRAE has been documented, this study identified three additional SRAEs
not currently assessed by expectancy questionnaires. These SRAEs may contribute
to high-risk sex when under the influence of alcohol and suggests the importance
of developing integrated alcohol-sexual risk reduction interventions for high
risk women.
PMID- 25110961
TI - Isolation and characterization of glycophorin from carp red blood cell membranes.
AB - We isolated a high-purity carp glycophorin from carp erythrocyte membranes
following extraction using the lithium diiodosalicylate (LIS)-phenol method and
streptomycin treatment. The main carp glycophorin was observed to locate at the
position of the carp and human band-3 proteins on an SDS-polyacrylamide gel. Only
the N-glycolylneuraminic acid (NeuGc) form of sialic acid was detected in the
carp glycophorin. The oligosaccharide fraction was separated into two components
(P-1 and P-2) using a Glyco-Pak DEAE column. We observed bacteriostatic activity
against five strains of bacteria, including two known fish pathogens. Fractions
from the carp erythrocyte membrane, the glycophorin oligosaccharide and the P-1
also exhibited bacteriostatic activity; whereas the glycolipid fraction and the
glycophorin fraction without sialic acid did not show the activity. The carp
glycophorin molecules attach to the flagellum of V. anguillarum or the cell
surface of M. luteus and inhibited bacterial growth.
PMID- 25110960
TI - Auxiliary subunits: shepherding AMPA receptors to the plasma membrane.
AB - Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated cation
channels that mediate excitatory signal transmission in the central nervous
system (CNS) of vertebrates. The members of the iGluR subfamily of alpha-amino-3
hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate
most of the fast excitatory signal transmission, and their abundance in the
postsynaptic membrane is a major determinant of the strength of excitatory
synapses. Therefore, regulation of AMPAR trafficking to the postsynaptic membrane
is an important constituent of mechanisms involved in learning and memory
formation, such as long-term potentiation (LTP) and long-term depression (LTD).
Auxiliary subunits play a critical role in the facilitation and regulation of
AMPAR trafficking and function. The currently identified auxiliary subunits of
AMPARs are transmembrane AMPA receptor regulatory proteins (TARPs), suppressor of
lurcher (SOL), cornichon homologues (CNIHs), synapse differentiation-induced gene
I (SynDIG I), cysteine-knot AMPAR modulating proteins 44 (CKAMP44), and germ cell
specific gene 1-like (GSG1L) protein. In this review we summarize our current
knowledge of the modulatory influence exerted by these important but still
underappreciated proteins.
PMID- 25110962
TI - Serum oxidative stress, visfatin and apelin in healthy women and those with
premenstrual syndrome.
AB - The aim of this study was to investigate whether there is a relationship between
premenstrual syndrome and oxidative stress, visfatin and apelin. The study
included 40 women with premenstrual syndrome and 40 healthy women. In all
subjects, serum visfatin, apelin and oxidative stress parameters were studied in
venous blood samples. The oxidative stress parameters were higher in the
premenstrual syndrome group than among the controls, but this difference did not
reach statistical significance (p > 0.05). It was found that total antioxidant
capacity was similar in both groups. For the insulin-serotonin cycle markers, no
significant difference was found between groups in terms of visfatin level (p =
0.893), although apelin was found to be significantly higher in the premenstrual
syndrome group when compared with the controls (p < 0.001). According to our
results, apelin can be used as an ancillary laboratory test in the diagnosis of
premenstrual syndrome.
PMID- 25110963
TI - Understanding spatial relationships in US: a computer-based training tool that
utilizes inexpensive off-the-shelf game controllers.
AB - The authors present a simulation-based ultrasonographic (US) training tool that
can help improve the understanding of spatial relationships in US. Use of a game
controller to simulate a US probe allows examination of different virtual three
dimensional (3D) objects. These 3D objects are either completely artificial
simple geometric objects (eg, spheres, tubes, and ellipsoids, or more complex
combinations thereof) or derived from photographed gross anatomic data (eg, the
Visible Human dataset [U.S. National Library of Medicine]) or clinical computed
tomographic (CT) data. The virtual US probe allows infinitely variable real-time
positioning of a "slice" that is displayed as a two-dimensional (2D) cross
sectional image and as part of a 3D view. Combining the 2D and 3D views helps
elucidate the spatial relationships between a 3D object and derived 2D images.
This training tool provides reliable real-time interactivity and is widely
available and easily affordable, since it utilizes standard personal computer
technology and off-the-shelf gaming hardware. For instance, it can be used at
home by medical students or residents as a complement to conventional US
training. In the future, this system could be adapted to support training for US
guided needle biopsy, with use of a second game controller to control the biopsy
needle. Furthermore, it could be used as a more general interactive visualization
tool for the evaluation of clinical 3D CT and magnetic resonance imaging data,
allowing efficient and intuitive real-time creation of oblique multiplanar
reformatted images.
PMID- 25110964
TI - New open-framework cobalt sulfate-oxalates based on molecular and chain-like
building blocks.
AB - Presented here are two novel open-framework cobalt sulfate-oxalates constructed
from molecular and chain-like building blocks. The two compounds have different
structures: an hcb-type layer with 20-ring windows and a mog-type framework with
12-ring channels. Amine molecules play dual roles in the two structures: as a
chelating ligand and a charge-balancing agent.
PMID- 25110965
TI - Short stories on zebrafish long noncoding RNAs.
AB - The recent re-annotation of the transcriptome of human and other model organisms,
using next-generation sequencing approaches, has unravelled a hitherto unknown
repertoire of transcripts that do not have a potential to code for proteins.
These transcripts have been largely classified into an amorphous class popularly
known as long noncoding RNAs (lncRNA). This discovery of lncRNAs in human and
other model systems have added a new layer to the understanding of gene
regulation at the transcriptional and post-transcriptional levels. In recent
years, three independent studies have discovered a number of lncRNAs expressed in
different stages of zebrafish development and adult tissues using a high
throughput RNA sequencing approach, significantly adding to the repertoire of
genes known in zebrafish. A subset of these transcripts also shows distinct and
specific spatiotemporal patterns of gene expression, pointing to a tight
regulatory control and potential functional roles in development, organogenesis,
and/ or homeostasis. This review provides an overview of the lncRNAs in zebrafish
and discusses how their discovery could provide new insights into understanding
biology, explaining mutant phenotypes, and helping in potentially modeling
disease processes.
PMID- 25110967
TI - Serotherapy for Ebola: back to the future.
PMID- 25110968
TI - Hidden victims of childhood vitiligo: impact on parents' mental health and
quality of life.
AB - This study aims to assess the impact of childhood vitiligo on the psychological
status and quality of life of their parents, and to determine how this varies
according to their children's disease condition. The study included 50 families
of children with vitiligo (a total of 75 participants) and 50 families of normal
children (a total of 79 participants). The psychosocial impact of the disease on
parents was measured using the Self-rated Health Measurement Scale (SRHMS) and
the Dermatitis Family Impact Questionnaire (DFI). SRHMS scores for parents of
children with vitiligo were significantly lower than for parents with normal
children. In addition, women had lower scores than men in the study group. The
mean DFI score in affected families was higher than in unaffected families.
Parents of children with vitiligo have significant psychological problems, and
their quality of life is poorer than for parents of normal children. In
conclusion, parents of children with vitiligo need as much care and attention as
their affected children.
PMID- 25110969
TI - Routine blood cultures for the febrile inpatient: a teachable moment.
PMID- 25110966
TI - Triheptanoin for glucose transporter type I deficiency (G1D): modulation of human
ictogenesis, cerebral metabolic rate, and cognitive indices by a food supplement.
AB - IMPORTANCE: Disorders of brain metabolism are multiform in their mechanisms and
manifestations, many of which remain insufficiently understood and are thus
similarly treated. Glucose transporter type I deficiency (G1D) is commonly
associated with seizures and with electrographic spike-waves. The G1D syndrome
has long been attributed to energy (ie, adenosine triphosphate synthetic) failure
such as that consequent to tricarboxylic acid (TCA) cycle intermediate depletion.
Indeed, glucose and other substrates generate TCAs via anaplerosis. However, TCAs
are preserved in murine G1D, rendering energy-failure inferences premature and
suggesting a different hypothesis, also grounded on our work, that consumption of
alternate TCA precursors is stimulated and may be detrimental. Second, common
ketogenic diets lead to a therapeutically counterintuitive reduction in blood
glucose available to the G1D brain and prove ineffective in one-third of
patients. OBJECTIVE: To identify the most helpful outcomes for treatment
evaluation and to uphold (rather than diminish) blood glucose concentration and
stimulate the TCA cycle, including anaplerosis, in G1D using the medium-chain,
food-grade triglyceride triheptanoin. DESIGN, SETTING, AND PARTICIPANTS:
Unsponsored, open-label cases series conducted in an academic setting. Fourteen
children and adults with G1D who were not receiving a ketogenic diet were
selected on a first-come, first-enrolled basis. INTERVENTION: Supplementation of
the regular diet with food-grade triheptanoin. MAIN OUTCOMES AND MEASURES: First,
we show that, regardless of electroencephalographic spike-waves, most seizures
are rarely visible, such that perceptions by patients or others are inadequate
for treatment evaluation. Thus, we used quantitative electroencephalographic,
neuropsychological, blood analytical, and magnetic resonance imaging cerebral
metabolic rate measurements. RESULTS: One participant (7%) did not manifest spike
waves; however, spike-waves promptly decreased by 70% (P = .001) in the other
participants after consumption of triheptanoin. In addition, the
neuropsychological performance and cerebral metabolic rate increased in most
patients. Eleven patients (78%) had no adverse effects after prolonged use of
triheptanoin. Three patients (21%) experienced gastrointestinal symptoms, and 1
(7%) discontinued the use of triheptanoin. CONCLUSIONS AND RELEVANCE:
Triheptanoin can favorably influence cardinal aspects of neural function in G1D.
In addition, our outcome measures constitute an important framework for the
evaluation of therapies for encephalopathies associated with impaired
intermediary metabolism.
PMID- 25110970
TI - Tunable exciton funnel using Moire superlattice in twisted van der Waals bilayer.
AB - A spatially varying bandgap drives exciton motion and can be used to funnel
energy within a solid (Nat. Photonics 2012, 6, 866-872). This bandgap modulation
can be created by composition variation (traditional heterojunction), elastic
strain, or in the work shown next, by a small twist between two identical
semiconducting atomic sheets, creating an internal stacking translation u(r) that
varies gently with position r and controls the local bandgap Eg(u(r)). Recently
synthesized carbon/boron nitride (Nat. Nanotechnol. 2013, 8, 119) and phosphorene
(Nat. Nanotechnol. 2014, 9, 372) may be used to construct this twisted
semiconductor bilayer that may be regarded as an in-plane crystal but an out-of
plane molecule, which could be useful in solar energy harvesting and
electroluminescence. Here, by first-principles methods, we compute the bandgap
map and delineate its material and geometric sensitivities. Eg(u(r)) is predicted
to have multiple local minima ("funnel centers") due to secondary or even
tertiary periodic structures in-plane, leading to a hitherto unreported pattern
of multiple "exciton flow basins". A compressive strain or electric field will
further enhance Eg-contrast in different regions of the pseudoheterostructure so
as to absorb or emit even broader spectrum of light.
PMID- 25110971
TI - Biofunctional constituent isolated from Citrullus colocynthis fruits and
structure-activity relationships of its analogues show acaricidal and
insecticidal efficacy.
AB - The acaricidal and insecticidal potential of the active constituent isolated from
Citrullus colocynthis fruits and its structurally related analogues was evaluated
by performing leaf disk, contact toxicity, and fumigant toxicity bioassays
against Tetranychus urticae, Sitophilus oryzae, and Sitophilus zeamais adults.
The active constituent of C. colocynthis fruits was isolated by chromatographic
techniques and was identified as 4-methylquinoline on the basis of spectroscopic
analyses. To investigate the structure-activity relationships, 4-methylquinoline
and its structural analogues were tested against mites and two insect pests. On
the basis of the LC50 values, 7,8-benzoquinoline was the most effective against
T. urticae. Quinoline, 8-hydroxyquinoline, 2-methylquinoline, 4-methylquinoline,
6-methylquinoline, 8-methylquinoline, and 7,8-benzoquinoline showed high
insecticidal activities against S. oryzae and S. zeamais regardless of the
application method. These results indicate that introduction of a functional
group into the quinoline skeleton and changing the position of the group have an
important influence on the acaricidal and insecticidal activities. Furthermore, 4
methylquinoline isolated from C. colocynthis fruits, along with its structural
analogues, could be effective natural pesticides for managing spider mites and
stored grain weevils.
PMID- 25110972
TI - The psychosocial impact of detention and deportation on U.S. migrant children and
families.
AB - Approximately 4.5 million U.S. citizen children live in mixed-status families, in
which at least 1 family member is an unauthorized migrant and therefore
vulnerable to detention and deportation from the United States (Passel & Cohn,
2011). This article critically examines the current state of the literature on
the psychosocial consequences of detention and deportation for unauthorized
migrants, mixed-status families, and their U.S.-born children. In particular,
drawing on social and psychological theory and research, we (a) review the impact
of parents' unauthorized status on children; (b) summarize the literature on the
impact of detention processes on psychosocial well-being; (c) describe the
dilemma faced by a mixed-status family when a parent faces deportation; (d)
examine the current social scientific literature on how parental deportation
impacts children and their families; and (e) summarize several policy
recommendations for protecting children and families.
PMID- 25110973
TI - Posttraumatic growth in children and youth: clinical implications of an emerging
research literature.
AB - Posttraumatic growth (PTG), positive change resulting from the struggle with
trauma, has garnered significant attention in the literature on adults. Recently,
the research base has begun to extend downward, and this literature indicates
that youth also evidence PTG-like changes. Researchers have sought to assess the
construct, examine its correlates, and understand the factors that contribute to
PTG in youth. Drawing from this work, this article considers clinical
implications for youth. After briefly describing the PTG construct, its
hypothesized process, and its distinction from resilience, the article focuses on
key themes in the literature and, with those findings as backdrop, ways in which
professionals can facilitate growth in youth who have experienced trauma. This
discussion situates PTG within the broader trauma literature and includes
specific applications used to date as well as the role of cultural factors.
Future directions--salient to practitioners and researchers alike--are
considered.
PMID- 25110974
TI - Sudden losses and negative appraisal in people with severe mental illness.
AB - Research on the impact of sudden or unexpected losses in people with severe
mental illness is scarce. The purpose of our study was to examine the
relationship between subjective distress from sudden losses in people with severe
mental illness and posttraumatic stress symptoms while controlling for gender,
psychiatric symptoms, and negative appraisals. As part of routine care, treatment
personnel collected data from 371 community mental health clients diagnosed with
a severe mental illness. Hierarchical linear regression revealed that negative
appraisals of the self and the world correlated significantly with posttraumatic
stress symptoms, and distress from losses accounted for the greatest amount of
variance in posttraumatic stress symptoms of the 6 traumas tested. When examined
by diagnostic group, only those with schizophrenia spectrum disorder showed a
significant association between distress from sudden losses and posttraumatic
stress symptoms. Relative to other factors including symptoms of severe mental
illness, distress from sudden losses in people with severe mental illness appears
to be strongly associated with posttraumatic stress symptoms.
PMID- 25110975
TI - Contemporary heterosexism on campus and psychological distress among LGBQ
students: the mediating role of self-acceptance.
AB - Contemporary heterosexism includes both overt and subtle discrimination. Minority
stress theory posits that heterosexism puts sexual minorities at risk for
psychological distress and other negative outcomes. Research, however, tends to
focus only on 1 form at a time, with minimal attention being given to subtle
heterosexism. Further, little is known about the connection between minority
stressors and underlying psychological mechanisms that might shape mental health
outcomes. Among a convenience sample of lesbian, gay, bisexual, and queer (LGBQ)
college students (n = 299), we investigated the role of blatant victimization and
LGBQ microaggressions, both together and separately, on psychological distress
and the mediating role of self-acceptance. We conducted structural equation
modeling to examine hypothesized relationships. Heterosexism was measured as
blatant victimization, interpersonal microaggressions, and environmental
microaggressions. Self-acceptance included self-esteem and internalized LGBTQ
pride. Anxiety and perceived stress comprised the psychological distress factor.
Our results suggest that students with greater atypical gender expression
experience, greater overall heterosexism and victimization, and younger students
experience more overall heterosexism, and undergraduates report more
victimization. Microaggressions, particularly environmental microaggressions, are
more influential on overall heterosexism than blatant victimization. Overall
heterosexism and microaggressions demonstrated main effects with self-acceptance
and distress, whereas victimization did not. Self-acceptance mediated the path
from discrimination to distress for both overall heterosexism and
microaggressions. Our findings advance minority stress theory research by
providing a nuanced understanding of the nature of contemporary discrimination
and its consequences, as well as illuminating the important role self-acceptance
plays as a mediator in the discrimination-psychological distress relationship.
PMID- 25110976
TI - Risk factors for suicidal behaviors among Filipino Americans: a data mining
approach.
AB - Filipino Americans have lower suicide rates than other Asian ethnic groups. The
present study examined risk factors for suicide ideation and attempt among
Filipino Americans with random forest. The data were from the Filipino American
Community Epidemiological Study (Takeuchi, 2011). The results showed that the
important predictors for suicide ideation were depressive disorder, substance use
disorder, and years in the United States. The important predictors for suicide
attempt were the number of family relatives and family conflict. Clinicians are
advised to investigate familial and cultural factors among Filipino Americans.
How family and cultural factors may affect suicidal behaviors were further
discussed.
PMID- 25110977
TI - Menstrual suppression for adolescents.
AB - PURPOSE OF REVIEW: The purpose of this review is to highlight the recent
literature and emerging data describing clinical situations in which menstrual
suppression may improve symptoms and quality of life for adolescents. A variety
of conditions occurring frequently in adolescents and young adults, including
heavy menstrual bleeding, and dysmenorrhea as well as gynecologic conditions such
as endometriosis and pelvic pain, can safely be improved or alleviated with
appropriate menstrual management. RECENT FINDINGS: Recent publications have
highlighted the efficacy and benefit of extended cycle or continuous combined
oral contraceptives, the levonorgestrel intrauterine device, and progestin
therapies for a variety of medical conditions. SUMMARY: This review places
menstrual suppression in an historical context, summarizes methods of hormonal
therapy that can suppress menses, and reviews clinical conditions for which
menstrual suppression may be helpful.
PMID- 25110978
TI - Risk factors for urinary, fecal, or double incontinence in women.
AB - PURPOSE OF REVIEW: To review recent, significant contributions to the medical
literature regarding the identification of factors which are associated with
urinary, fecal, and double incontinence in women. RECENT FINDINGS: Approximately
one out of five women suffers from moderate to severe urinary incontinence, one
out of 10 has fecal incontinence, and 2.5% have double incontinence of urine and
stool. Obesity is primarily associated with urinary incontinence, whereas
diabetes mellitus is a stronger risk factor for fecal incontinence. Double
incontinence is primarily associated with advanced age, depression, and
decompensating medical conditions that denote frailty. SUMMARY: Knowledge
regarding which clinical conditions and patient characteristics are strongly
associated with each type of incontinence helps identify those patients who are
at risk and aids in targeted screening and treatment programs.
PMID- 25110979
TI - Multidisciplinary care for individuals with disorders of sex development.
AB - PURPOSE OF REVIEW: Recommendations regarding the care of individuals with
disorders of sex development include that care be provided by multidisciplinary
teams. This article will discuss team composition and function as well as the
role of the gynecologist and barriers to such care. RECENT FINDINGS: Many
barriers to multidisciplinary care exist, but recent reports stress the roles of
different team members as well as tools for planning and implementation of such a
team that may help to overcome such barriers. All current recommendations include
the participation of a gynecologist in the disorders of sex development team.
Gynecologists are in the unique position to continue to provide care as these
individuals mature into adulthood. SUMMARY: Multidisciplinary care for patients
with disorders of sex development is recommended and gynecologists provide unique
expertise.
PMID- 25110980
TI - Uncovering the Meaning of Home Care Using an Arts-Based and Qualitative Approach.
AB - The need for home care is increasing in Canada, yet little is known about the
home care experience of clients and their families. Uncovering the meaning of the
home care experience is an important step towards developing understanding and
public awareness. We explored the experiences of home care using arts-based
methods and individual interviews with 11 participants (one client and 10 family
caregivers). Participants discussed the numerous ways formal home care and family
caregiving affected their lives, how they coped with these effects, their
experiences in hospitals or assisted living facilities, and aspects of the home
care experience they liked or disliked. Participants agreed that home care
facilitated a better quality of life for families and clients, although they
acknowledged some challenges with it. The artistic outputs produced by
participants facilitated interview dialogue and fostered understanding of key
themes within the research team.
PMID- 25110981
TI - Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease
in rat collagen-induced arthritis.
AB - INTRODUCTION: The inflammatory reflex is a physiological mechanism through which
the nervous system maintains immunologic homeostasis by modulating innate and
adaptive immunity. We postulated that the reflex might be harnessed
therapeutically to reduce pathological levels of inflammation in rheumatoid
arthritis by activating its prototypical efferent arm, termed the cholinergic
anti-inflammatory pathway. To explore this, we determined whether electrical
neurostimulation of the cholinergic anti-inflammatory pathway reduced disease
severity in the collagen-induced arthritis model. METHODS: Rats implanted with
vagus nerve cuff electrodes had collagen-induced arthritis induced and were
followed for 15 days. Animals underwent active or sham electrical stimulation
once daily from day 9 through the conclusion of the study. Joint swelling,
histology, and levels of cytokines and bone metabolism mediators were assessed.
RESULTS: Compared with sham treatment, active neurostimulation of the cholinergic
anti-inflammatory pathway resulted in a 52% reduction in ankle diameter (p =
0.02), a 57% reduction in ankle diameter (area under curve; p = 0.02) and 46%
reduction overall histological arthritis score (p = 0.01) with significant
improvements in inflammation, pannus formation, cartilage destruction, and bone
erosion (p = 0.02), accompanied by numerical reductions in systemic cytokine
levels, not reaching statistical significance. Bone erosion improvement was
associated with a decrease in serum levels of receptor activator of NF-kappaB
ligand (RANKL) from 132+/-13 to 6+/-2 pg/mL (mean+/-SEM, p = 0.01). CONCLUSIONS:
The severity of collagen-induced arthritis is reduced by neurostimulation of the
cholinergic anti-inflammatory pathway delivered using an implanted electrical
vagus nerve stimulation cuff electrode, and supports the rationale for testing
this approach in human inflammatory disorders.
PMID- 25110982
TI - Association between duration of carbon dioxide pneumoperitoneum during
laparoscopic abdominal surgery and hepatic injury: a meta-analysis.
AB - BACKGROUND: The aim of this study is to accurately assess whether the duration of
intraoperative carbon dioxide pneumoperitoneum (CDP) is associated with the
induction of hepatic injury. METHODS: We conducted a systematic review of PubMed,
Embase, and Cochrane Library databases (through February 2014) to identify case
match studies that compared high-pressure CDP with low-pressure CDP or varied the
duration of CDP in patients who underwent abdominal surgery. The outcome of
interest was postoperative liver function (ALT, AST, TB). RESULTS: Eleven
comparative studies involving 2,235 participants were included. Overall, levels
of ALT, AST, and TB (on postoperative days 1, 3, and 7) were significantly
elevated in the study groups. However, the results of the subanalyses of those
who underwent laparoscopic colorectal cancer resection (LCR) versus open
colorectal cancer resection (OCR) and those who underwent laparoscopic gastric
bypass (LGBP) versus open gastric bypass (OGBP) were inconsistent. CONCLUSIONS:
The current evidence suggests that the duration of CDP during laparoscopic
abdominal surgery may be associated with hepatic injury. Additional large-scale,
randomized, controlled trials are urgently needed to further confirm this.
PMID- 25110983
TI - Bioaccumulation and toxicity of CuO nanoparticles by a freshwater invertebrate
after waterborne and dietborne exposures.
AB - The incidental ingestion of engineered nanoparticles (NPs) can be an important
route of uptake for aquatic organisms. Yet, knowledge of dietary bioavailability
and toxicity of NPs is scarce. Here we used isotopically modified copper oxide
((65)CuO) NPs to characterize the processes governing their bioaccumulation in a
freshwater snail after waterborne and dietborne exposures. Lymnaea stagnalis
efficiently accumulated (65)Cu after aqueous and dietary exposures to (65)CuO
NPs. Cu assimilation efficiency and feeding rates averaged 83% and 0.61 g g(-1)
d(-1) at low exposure concentrations (<100 nmol g(-1)), and declined by nearly
50% above this concentration. We estimated that 80-90% of the bioaccumulated
(65)Cu concentration in L. stagnalis originated from the (65)CuO NPs, suggesting
that dissolution had a negligible influence on Cu uptake from the NPs under our
experimental conditions. The physiological loss of (65)Cu incorporated into
tissues after exposures to (65)CuO NPs was rapid over the first days of
depuration and not detectable thereafter. As a result, large Cu body
concentrations are expected in L. stagnalis after exposure to CuO NPs. To the
degree that there is a link between bioaccumulation and toxicity, dietborne
exposures to CuO NPs are likely to elicit adverse effects more readily than
waterborne exposures.
PMID- 25110984
TI - Self-assembly of a tripeptide into a functional coating that resists fouling.
AB - This communication describes the self-assembly of a tripeptide into a functional
coating that resists biofouling. Using this peptide-based coating we were able to
prevent protein adsorption and interrupt biofilm formation. This coating can be
applied on numerous substrates and therefore can serve in applications related to
health care, marine and water treatment.
PMID- 25110985
TI - Relationships Among Meeting Physical-Activity Guidelines and Health Risk
Behaviors.
AB - BACKGROUND: Young adults have the highest participation in physical activity but
also have the highest incidence rates of binge drinking, cigarette smoking, and
smokeless tobacco use. We examined these factors to determine whether there are
relationships among physical activity and health risk behaviors. METHODS: We
conducted correlation and chi2 analyses using the American College Health
Association-National College Health Assessment fall 2009 data set (N = 34,208) to
examine the relationship among meeting physical-activity guidelines, binge
drinking, and tobacco use among survey participants. RESULTS: The data suggest a
positive relationship between meeting physical-activity guidelines and binge
drinking, with the strongest relationship between those reporting binge drinking
4 times in a 2-week period. Meeting physical-activity guidelines was negatively
associated with cigarette use but positively associated with all other types of
tobacco use. CONCLUSIONS: Associations between physical activity and binge
drinking episodes indicate a need to address the relationship between heavy
drinking and alcohol dependence and physical-activity behavior patterns. Further
studies should examine relationships between physical activity and binge drinking
in other age groups. Results also suggest the need to examine differing
associations between physical activity and types of tobacco use.
PMID- 25110987
TI - Dendrimersomes with photodegradable membranes for triggered release of
hydrophilic and hydrophobic cargo.
AB - Amphiphilic Janus dendrimers containing first through third generation (G1-G3)
photodegradable hydrophobic blocks were synthesized and their self-assembly in
water was studied. While the G1 and G2 systems formed solid aggregates, the G3
system self-assembled to form dendrimersomes. These dendrimersomes were
demonstrated to degrade upon irradiation with UV light, and exhibited triggered
release of both hydrophobic and hydrophilic payloads.
PMID- 25110986
TI - On simplified global nonlinear function for fitness landscape: a case study of
inverse protein folding.
AB - The construction of fitness landscape has broad implication in understanding
molecular evolution, cellular epigenetic state, and protein structures. We
studied the problem of constructing fitness landscape of inverse protein folding
or protein design, with the aim to generate amino acid sequences that would fold
into an a priori determined structural fold which would enable engineering novel
or enhanced biochemistry. For this task, an effective fitness function should
allow identification of correct sequences that would fold into the desired
structure. In this study, we showed that nonlinear fitness function for protein
design can be constructed using a rectangular kernel with a basis set of proteins
and decoys chosen a priori. The full landscape for a large number of protein
folds can be captured using only 480 native proteins and 3,200 non-protein decoys
via a finite Newton method. A blind test of a simplified version of fitness
function for sequence design was carried out to discriminate simultaneously 428
native sequences not homologous to any training proteins from 11 million
challenging protein-like decoys. This simplified function correctly classified
408 native sequences (20 misclassifications, 95% correct rate), which outperforms
several other statistical linear scoring function and optimized linear function.
Our results further suggested that for the task of global sequence design of 428
selected proteins, the search space of protein shape and sequence can be
effectively parametrized with just about 3,680 carefully chosen basis set of
proteins and decoys, and we showed in addition that the overall landscape is not
overly sensitive to the specific choice of this set. Our results can be
generalized to construct other types of fitness landscape.
PMID- 25110988
TI - Behavior of highly diluted electrolytes in strong electric fields-prevention of
alumina deposition on grading electrodes in HVDC transmission modules by CO2
induced pH-control.
AB - Alumina deposition on platinum grading electrodes in high voltage direct current
(HVDC) transmission modules is an unsolved problem that has been around for more
than three decades. This is due to the unavoidable corrosion of aluminum heat
sinks that causes severe damage to electrical power plants and losses in the
range of a million Euro range per day in power outage. Simple experiments in a
representative HV test setup showed that aluminates at concentrations even below
10(-8) mol L(-1) can deposit on anodes through neutralization by protons produced
in de-ionized water (kappa<=0.15 MUS cm(-1)) at 20-35 kV (8 mA) per electrode. In
this otherwise electrolyte-poor aqueous environment, the depositions are formed
three orders of magnitude below the critical precipitation concentration at pH 7!
In the presence of an inert electrolyte such as TMAT (tetramethylammonium-p
toluenesulfonate), at a concentration level just above that of the total
dissolved aluminum, no deposition was observed. Deposition can be also prevented
by doping with CO2 gas at a concentration level that is magnitudes lower than
that of the dissolved aluminum. From an overview of aqueous aluminum chemistry,
the mystery of the alumina deposition process and its inhibition by CO2 is
experimentally resolved and fully explained by field accumulation and repulsion
models in synergism with acid-base equilibria. The extraordinary size of the
alumina depositions is accounted for in terms of proton tunneling through
"hydrated" alumina, which is supported by quantum chemical calculations. As a
consequence, pulse-purging with pure CO2 gas is presented as a technical solution
to prevent the deposition of alumina.
PMID- 25110989
TI - Measuring the pK/pI of biomolecules using X-ray photoelectron spectroscopy.
AB - Dissociation constants of GG-X-GG and X5 peptides (X = G, D, H, or K), and bovine
albumin (BSA) and fibronectin (FN) were measured by X-ray photoelectron
spectroscopy (XPS) in ultrahigh vacuum at room temperature. The biomolecules were
deposited on Au substrates by drying 2.0 MUL drops of 1.0 MUg MUL(-1) stock
solutions in 100 mM sodium phosphate buffers (pH 1-12) at room temperature.
Because of the ~+1.3 eV shift in binding energy (BE) of protonated amines, pK
values of basic amino acids were calculated by plotting the fraction of
protonated amines as a function of solution pH. Similarly, the BE of carboxyl
groups shifted ~-1.3 eV upon deprotonation. While C 1s spectra were convoluted by
the multiple chemical states of carbon present in the samples, the ratio of the C
1s components centered at BE = 289.0 +/- 0.4 and BE = 287.9 +/- 0.3 proved to
reliably assess deprotonation of carboxyl groups. The pK values for the Asp (3.1
and 2.4), His (6.7), and Lys (11.3 and 10.6) peptides, and the pI of BSA (4.8)
and FN (5.7), were consistent with published values; thus, these methods could
potentially be used to determine the dissociation constants of surface-bound
biomolecules.
PMID- 25110990
TI - A normal ovary in an abnormal location: A case of torsion.
AB - The clinical and radiologic diagnosis of adnexal torsion is challenging. The
patient's history, physical examination, and laboratory evaluation may overlap
significantly with other causes of abdominal pain. Ultrasound is the most common
radiologic tool to assess for torsion, and the imaging findings can be equally
equivocal. We present a case of adnexal torsion in an 18-year-old emergency room
patient with abdominal pain, diagnosed by ultrasound based solely on an abnormal
medial position of the ovary-a finding that has been only rarely mentioned in the
literature, and never in isolation.
PMID- 25110991
TI - Smarter hospital communication: secure smartphone text messaging improves
provider satisfaction and perception of efficacy, workflow.
AB - BACKGROUND: Though current hospital paging systems are neither efficient
(callbacks disrupt workflow), nor secure (pagers are not Health Insurance
Portability and Accountability Act [HIPAA]-compliant), they are routinely used to
communicate patient information. Smartphone-based text messaging is a potentially
more convenient and efficient mobile alternative; however, commercial cellular
networks are also not secure. OBJECTIVE: To determine if augmenting one-way
pagers with Medigram, a secure, HIPAA-compliant group messaging (HCGM)
application for smartphones, could improve hospital team communication. DESIGN:
Eight-week prospective, cluster-randomized, controlled trial SETTING: Stanford
Hospital INTERVENTION: Three inpatient medicine teams used the HCGM application
in addition to paging, while two inpatient medicine teams used paging only for
intra-team communication. MEASUREMENTS: Baseline and post-study surveys were
collected from 22 control and 41 HCGM team members. RESULTS: When compared with
paging, HCGM was rated significantly (P < 0.05) more effective in: (1) allowing
users to communicate thoughts clearly (P = 0.010) and efficiently (P = 0.009) and
(2) integrating into workflow during rounds (P = 0.018) and patient discharge (P
= 0.012). Overall satisfaction with HCGM was significantly higher (P = 0.003).
85% of HCGM team respondents said they would recommend using an HCGM system on
the wards. CONCLUSIONS: Smartphone-based, HIPAA-compliant group messaging
applications improve provider perception of in-hospital communication, while
providing the information security that paging and commercial cellular networks
do not.
PMID- 25110992
TI - Identification of cleavage sites leading to the shed form of the anti-aging
protein klotho.
AB - Membrane protein shedding is a critical step in many normal and pathological
processes. The anti-aging protein klotho (KL), mainly expressed in kidney and
brain, is secreted into the serum and CSF, respectively. KL is proteolytically
released, or shed, from the cell surface by ADAM10 and ADAM17, which are the
alpha-secretases that also cleave the amyloid precursor protein and other
proteins. The transmembrane KL is a coreceptor with the FGF receptor for FGF23,
whereas the shed form acts as a circulating hormone. However, the precise
cleavage sites in KL are unknown. KL contains two major cleavage sites: one close
to the juxtamembrane region and another between the KL1 and KL2 domains. We
identified the cleavage site involved in KL release by mutating potential
sheddase(s) recognition sequences and examining the production of the KL
extracellular fragments in transfected COS-7 cells. Deletion of amino acids T958
and L959 results in a 50-60% reduction in KL shedding, and an additional P954E
mutation results in further reduction of KL shedding by 70-80%. Deletion of amino
acids 954-962 resulted in a 94% reduction in KL shedding. This mutant also had
moderately decreased cell surface expression, yet had overall similar subcellular
localization as that of WT KL, as demonstrated by immunofluorescence. Cleavage
resistant mutants could function as a FGFR coreceptor for FGF23, but they lost
activity as a soluble form of KL in proliferation and transcriptional reporter
assays. Cleavage between the KL1 and KL2 domains is dependent on juxtamembrane
cleavage. Our results shed light onto mechanisms underlying KL release from the
cell membrane and provide a target for potential pharmacologic interventions
aimed at regulating KL secretion.
PMID- 25110994
TI - Feasibility of reirradiation in the treatment of locally recurrent rectal cancer
(Br J Surg 2014; 101: 1280-1289).
PMID- 25110993
TI - Thirty-day hospital readmissions in systemic lupus erythematosus: predictors and
hospital- and state-level variation.
AB - OBJECTIVE: Systemic lupus erythematosus (SLE) has one of the highest hospital
readmission rates among chronic conditions. This study was undertaken to identify
patient-level, hospital-level, and geographic predictors of 30-day hospital
readmissions associated with SLE. METHODS: Using hospital discharge databases
from 5 geographically dispersed states, we studied all-cause readmission of SLE
patients between 2008 and 2009. We evaluated each hospitalization as a possible
index event leading up to a readmission, our primary outcome. We accounted for
clustering of hospitalizations within patients and within hospitals and adjusted
for hospital case mix. Using multilevel mixed-effects logistic regression, we
examined factors associated with 30-day readmission and calculated risk
standardized hospital-level and state-level readmission rates. RESULTS: We
examined 55,936 hospitalizations among 31,903 patients with SLE. Of these
hospitalizations, 9,244 (16.5%) resulted in readmission within 30 days. In
adjusted analyses, age was inversely related to risk of readmission. African
American and Hispanic patients were more likely to be readmitted than white
patients, as were those with Medicare or Medicaid insurance (versus private
insurance). Several clinical characteristics of lupus, including nephritis,
serositis, and thrombocytopenia, were associated with readmission. Readmission
rates varied significantly between hospitals after accounting for patient-level
clustering and hospital case mix. We also found geographic variation, with risk
adjusted readmission rates lower in New York and higher in Florida as compared to
California. CONCLUSION: We found that ~1 in 6 hospitalized patients with SLE were
readmitted within 30 days of discharge, with higher rates among historically
underserved populations. Significant geographic and hospital-level variation in
risk-adjusted readmission rates suggests potential for quality improvement.
PMID- 25110998
TI - One-pot transformation of cellobiose to formic acid and levulinic acid over ionic
liquid-based polyoxometalate hybrids.
AB - Currently, levulinic acid (LA) and formic acid (FA) are considered as important
carbohydrates for the production of value-added chemicals. Their direct
production from biomass will open up a new opportunity for the transformation of
biomass resource to valuable chemicals. In this study, one-pot transformation of
cellobiose into LA and FA was demonstrated, using a series of multiple-functional
ionic liquid-based polyoxometalate (IL-POM) hybrids as catalytic materials. These
IL-POMs not only markedly promoted the production of valuable chemicals including
LA, FA and monosaccharides with high selectivities, but also provided great
convenience of the recovery and the reuse of the catalytic materials in an
environmentally friendly manner. Cellobiose conversion of 100%, LA selectivity of
46.3%, and FA selectivity of 26.1% were obtained at 423 K and 3 MPa for 3 h in
presence of oxygen. A detailed catalytic mechanism for the one-pot transformation
of cellobiose was also presented.
PMID- 25110999
TI - Late mortality among 5-year survivors of early onset cancer: a population-based
register study.
AB - To date, only few studies have been published documenting late mortality among
early onset cancer survivors, especially regarding young adulthood (YA)
malignancies. Our nation-wide population-based registry study provides
information concerning cause-specific long-term mortality among 16,769 5-year
survivors of early onset cancer (aged 0-34 years at diagnosis), with follow-up
for death extending from 1971 through 2012. A sibling cohort and population data
were used as reference. The overall standardized mortality ratio (SMR) of cancer
patients was 4.6-fold, (95% CI 4.4-4.8). Highest SMRs were found for malignancies
(12.8, 95% CI 12.3-13.3), infectious (4.8, 95%CI 2.9-6.7) and cardiovascular
diseases (1.9, 95% CI 1.7-2.1). Malignancies and cardiovascular diseases
accounted for the largest number of deaths. Childhood and YA cancer survivors
with the same primary cancer site had a similarly elevated overall SMR with the
exception of markedly higher SMRs after childhood Hodgkin lymphoma. The highest
cumulative non-malignancy-related mortality was due to cardiovascular disease
with a steady rise throughout the follow-up, but strongly dependent on the
primary cancer site and age at diagnosis. In childhood cancer survivors, the
cumulative cardiovascular mortality did not reduce over time. However, overall
and malignancy-related mortality showed a declining tendency towards the most
recent periods after both, childhood and YA cancer. Our findings on non
malignancy-related mortality stress the need to set up long-term individual
follow-up with a focus on cardiovascular late effects for early onset cancer
survivors, especially for YA cancer survivors still lacking those.
PMID- 25111000
TI - New insights on the antidepressant discontinuation syndrome.
AB - OBJECTIVE: Antidepressants are at best 50-55% effective. Non-compliance and the
antidepressant discontinuation syndrome (ADS) are causally related yet poorly
appreciated. While ADS is associated with most antidepressants, agomelatine seems
to be devoid of such risk. We review the neurobiology and clinical consequences
of antidepressant non-compliance and the ADS. Agomelatine is presented as a
counterpoint to learn more on how ADS risk is determined by pharmacokinetics and
pharmacology. DESIGN: The relevant literature is reviewed through a MEDLINE
search via PubMed, focusing on agomelatine and clinical and preclinical research
on ADS. RESULTS: Altered serotonergic dysfunction appears central to ADS so that
how an antidepressant targets serotonin will determine its relative risk for
inducing ADS and thereby affect later treatment outcome. Low ADS risk with
agomelatine versus other antidepressants can be ascribed to its unique
pharmacokinetic characteristics as well as its distinctive actions on serotonin,
including melatonergic, monoaminergic and glutamatergic-nitrergic systems.
CONCLUSIONS: This review raises awareness of the long-term negative aspects of
non-compliance and inappropriate antidepressant discontinuation, and suggests
possible approaches to "design-out" a risk for ADS. It reveals intuitive and
rational ideas for antidepressant drug design, and provides new thoughts on
antidepressant pharmacology, ADS risk and how these affect long-term outcome.
PMID- 25111001
TI - Anticoagulant therapy in head injury-associated cerebral sinovenous thrombosis in
children.
AB - BACKGROUND: Head injury is a risk factor for cerebral sinovenous thrombosis
(CSVT) in children. Literature concerning head injury-associated CSVT (HIA-CSVT)
is scarce. Data supporting safety and efficacy of anticoagulant therapy (ACT) in
childhood CSVT is emerging. However, intracranial hemorrhage (ICH) occurs
frequently in children with HIA-CSVT at diagnosis making initiation of ACT
controversial due to the fear of worsening of ICH. PROCEDURE: We conducted a
retrospective descriptive review of a consecutive cohort of children with HIA
CSVT from 1998 to 2012. RESULTS: Twenty patients (14 males, mean age 7 years)
with HIA-CSVT were identified. Most (19/20 [95%]) had significant ICH at
diagnosis. None received ACT at diagnosis. Fourteen (70%) were later (median 7
days post-trauma, range 2-48 days) treated with ACT due to CSVT persistence
(nine) and propagation (five), despite ICH in 13. None of the treated patients,
including the 13 with pre-existing ICH, had significant worsening of hemorrhage.
Three (21%) treated patients had minor asymptomatic extension of their hemorrhage
and further ACT was withheld. No patient died while on ACT. No patient
experienced CSVT propagation on ACT. Clinical outcomes were normal (no neurologic
deficits) in 5/20(25%), mild neurological deficits in 10/20(50%), and moderate
severe neurological deficits in 5/20(25%). Small sample size did not permit
assessment of the effect of ACT on outcome. CONCLUSIONS: Anticoagulant therapy is
safe in selected children with HIA-CSVT. ICH is not an absolute contraindication
to ACT in children with HIA-CSVT.
PMID- 25111002
TI - Distribution and presumed proliferation of macrophages in inflammatory diseases
of the ocular adnexae.
AB - PURPOSE: The aim of this article is to investigate whether macrophages show a
proliferative activity (as indicated by Ki67 expression) and their distribution
at the site of inflammation. MATERIALS AND METHODS: Six different macrophage
containing lesions from six different patients (four females, two males; age
range: 16-58 years) were stained for macrophage markers (CD68, CD163) and Ki67 by
immunohistochemistry. Immunofluorescence techniques were used to investigate dual
labeling of the specimens for CD68, CD163 and Ki67, respectively. RESULTS: With
immunofluorescence staining, scattered cells in all specimens were dual-labeled
for CD68-Ki67 and CD163-Ki67. All lesions were composed of mixed infiltrates of
M1 (CD68+CD163-) and M2 (CD68+CD163+) macrophages. The center of epithelioid-cell
granulomas and foreign body giant cells was exclusively composed of M1
macrophages. CONCLUSIONS: This study shows that CD68+ and CD163+ cells express
Ki67, a marker for proliferative activity at the site of inflammation. Until
recently, macrophages were regarded as end-differentiated cells without mitotic
activity. Since self-renewal of M1 and M2 macrophages has been described in the
literature, staining of macrophages with Ki67 may indicate proliferative activity
or at least an activation state. The distribution of macrophages in classic
granulomatous lesions with only M1 macrophages in the avascular center represents
an immune response to foreign body material, whereas the proangiogenic M2
macrophages are located mostly in the surrounding inflammatory tissue and seem to
be mandatory for the vascularization of the inflammatory tissue.
PMID- 25111003
TI - Random whole metagenomic sequencing for forensic discrimination of soils.
AB - Here we assess the ability of random whole metagenomic sequencing approaches to
discriminate between similar soils from two geographically distinct urban sites
for application in forensic science. Repeat samples from two parklands in
residential areas separated by approximately 3 km were collected and the DNA was
extracted. Shotgun, whole genome amplification (WGA) and single arbitrarily
primed DNA amplification (AP-PCR) based sequencing techniques were then used to
generate soil metagenomic profiles. Full and subsampled metagenomic datasets were
then annotated against M5NR/M5RNA (taxonomic classification) and SEED Subsystems
(metabolic classification) databases. Further comparative analyses were performed
using a number of statistical tools including: hierarchical agglomerative
clustering (CLUSTER); similarity profile analysis (SIMPROF); non-metric
multidimensional scaling (NMDS); and canonical analysis of principal coordinates
(CAP) at all major levels of taxonomic and metabolic classification. Our data
showed that shotgun and WGA-based approaches generated highly similar metagenomic
profiles for the soil samples such that the soil samples could not be
distinguished accurately. An AP-PCR based approach was shown to be successful at
obtaining reproducible site-specific metagenomic DNA profiles, which in turn were
employed for successful discrimination of visually similar soil samples collected
from two different locations.
PMID- 25111004
TI - Immunoglobulin light chain amyloidosis is diagnosed late in patients with
preexisting plasma cell dyscrasias.
AB - AL amyloidosis (AL) is rare and frequently remains undiagnosed until organ
function is compromised, even among patients with known pre-existing untreated
plasma cell dyscrasias (PCD). We identified 168 patients with AL amyloidosis who
had a prior untreated PCD. The earliest symptom or sign (s/s) was defined as the
first symptom reported by the patient that could be attributed to organ
dysfunction caused by AL. The interval from the time of development of s/s to the
establishment of diagnosis of AL (Interval-SA) was calculated. PCD diagnosis
preceded recorded onset of s/s in 75% (114/152) of patients, with a median
interval-SA for this group of 10 months. PCD was diagnosed after s/s in 25%
(38/152) of patients, with a median interval-SA of 20 months. Overall survival
(OS) from diagnosis of AL was not different between the two groups. AL
amyloidosis patients with an identified pre-existing PCD had less advanced
cardiac disease at AL diagnosis when compared to a control group of AL patients
without pre-identified PCD. Long-term OS was not significantly superior among
patients with a pre-identified PCD. In patients with "asymptomatic" PCD, symptoms
and signs of AL amyloidosis should be solicited, since timely diagnosis is
important in AL amyloidosis.
PMID- 25111006
TI - Hyperpolarized [1,(13)C]pyruvate in lysed human erythrocytes: effects of co
substrate supply on reaction time courses.
AB - Hyperpolarized [1,(13)C]pyruvate was injected rapidly into haemolysates in which
hydrolysis of nicotinamide adenine dinucleotide (phosphate) (NAD(P))/NAD(P)H had
been inhibited with nicotinamide. Haemolysates provide a stable glycolytic system
in which membrane permeability is not a flux-controlling step, and they enable
the concentration of NADH to be adjusted experimentally while keeping the rest of
the sample with the same composition as that of the cytoplasm of the cell (albeit
diluted twofold at the time of injection of the [1,(13)C]pyruvate). We showed
that the maximum amplitude of the (13)C NMR signal from the [1,(13)C]L-lactate,
produced from [1,(13)C]pyruvate, and the time at which it occurred was dependent
on NADH concentration, as predicted by enzyme-kinetic analysis. The main feature
of such curves was dictated by the immediacy of the supply of the co-substrate of
lactate dehydrogenase (LDH, EC 1.1.1.27), and we posit that this also pertains in
vivo in various tissues including neoplasms. By constructing an appropriate
mathematical model and by using a Markov-chain Monte Carlo approach, we fitted
experimental data to estimate LDH and NADH concentrations. Experiments carried
out with only endogenous NADH present enabled the estimation of its effective
concentration in human RBCs; the ability to make this estimate is a special
feature of the rapid-dissolution dynamic nuclear polarization method. We found an
endogenous NADH concentration in human RBCs two to four times higher than
previously reported.
PMID- 25111005
TI - RAD9 enhances radioresistance of human prostate cancer cells through regulation
of ITGB1 protein levels.
AB - BACKGROUND: Mouse embryonic stem cells null for Rad9 are sensitive to deleterious
effects of ionizing radiation exposure. Likewise, integrin beta1 is a known
radioprotective factor. Previously, we showed that RAD9 downregulation in human
prostate cancer cells reduces integrin beta1 protein levels and ectopic
expression of Mrad9 restores inherent high levels. METHODS: We used RNA
interference to knockdown Rad9 expression in PC3 and DU145 prostate cancer cells.
These cells were then exposed to ionizing radiation, and integrin beta1 protein
levels were measured by immunoblotting. Survival of irradiated cells was measured
by clonogenicity, cell cycle analysis, PARP-1 cleavage, and trypan blue
exclusion. RESULTS: The function of RAD9 in controlling integrin beta1 expression
is unique and not shared by the other members of the 9-1-1 complex, HUS1 and
RAD1. RAD9 or integrin beta1 silencing sensitizes DU145 and PC3 cells to ionizing
radiation. Irradiation of DU145 cells with low levels of RAD9 induces cleavage of
PARP-1 protein. High levels of ionizing radiation have no effect on integrin
beta1 protein levels. However, when RAD9 downregulation is combined with 10 Gy of
ionizing radiation in DU145 or PC3 cells, there is an additional 50%
downregulation of integrin beta1 compared with levels in unirradiated RAD9
knockdown cells. Finally, PC3 cells growing on fibronectin display increased
radioresistance. However, PC3 cells with RAD9 knockdown are no longer protected
by fibronectin after treatment with ionizing radiation. CONCLUSIONS:
Downregulation of RAD9 when combined with ionizing radiation results in reduction
of ITGB1 protein levels in prostate cancer cells, and increased lethality.
PMID- 25111007
TI - Strongly correlated alignment of fluorinated 5,11
bis(triethylgermylethynyl)anthradithiophene crystallites in solution-processed
field-effect transistors.
AB - The crystallinity of an organic semiconductor film determines the efficiency of
charge transport in electronic devices. This report presents a micro-to-nanoscale
investigation on the crystal growth of fluorinated 5,11
bis(triethylgermylethynyl)anthradithiophene (diF-TEG-ADT) and its implication for
the electrical behavior of organic field-effect transistors (OFETs). diF-TEG-ADT
exhibits remarkable self-assembly through spin-cast preparation, with highly
aligned edge-on stacking creating a fast hole-conducting channel for OFETs.
PMID- 25111008
TI - Microwave-assisted formation of organic monolayers from 1-alkenes on silicon
carbide.
AB - The rate of formation of covalently linked organic monolayers on HF-etched
silicon carbide (SiC) is greatly increased by microwave irradiation. Upon
microwave treatment for 60 min at 100 degrees C (60 W), 1-alkenes yield densely
packed, covalently attached monolayers on flat SiC surfaces, a process that
typically takes 16 h at 130 degrees C under thermal conditions. This approach
was extended to SiC microparticles. The monolayers were characterized by X-ray
photoelectron spectroscopy and static water contact angle measurements. The
microwave-assisted reaction is compatible with terminal functionalities such as
alkenes that enable subsequent versatile "click" chemistry reactions, further
broadening the range and applicability of chemically modified SiC surfaces.
PMID- 25111009
TI - Structure and conformation of the medium-sized chlorophosphazene rings.
AB - Medium-sized cyclic oligomeric phosphazenes [PCl2N]m (where m = 5-9) that were
prepared from the reaction of PCl5 and NH4Cl in refluxing chlorobenzene have been
isolated by a combination of sublimation/extraction and column chromatography
from the predominant products [PCl2N]3 and [PCl2N]4. The medium-sized rings
[PCl2N]m have been characterized by electrospray ionization-mass spectroscopy
(ESI-MS), their (31)P chemical shifts have been reassigned, and their T1
relaxation times have been obtained. Crystallographic data has been recollected
for [PCl2N]5, and the crystal structures of [PCl2N]6, and [PCl2N]8 are reported.
Halogen-bonding interactions were observed in all the crystal structures of
cyclic [PCl2N]m (m = 3-5, 6, 8). The crystal structures of [P(OPh)2N]7 and
[P(OPh)2N]8, which are derivatives of the respective [PCl2N]m, are also reported.
Comparisons of the intermolecular forces and torsion angles of [PCl2N]8 and
[P(OPh)2N]8 with those of three other octameric rings are described. The
comparisons show that chlorophosphazenes should not be considered prototypical,
in terms of solid-state structure, because of the strong influence of halogen
bonding.
PMID- 25111010
TI - Triterpenoids of Ganoderma theaecolum and their hepatoprotective activities.
AB - Five new lanostane triterpenoids, ganoderic acid XL1 (1), ganoderic acid XL2 (2),
20-hydroxy-ganoderic acid AM1 (3), ganoderenic acid AM1 (4) and ganoderesin C
(5), together with five known triterpenoids (6-10) were isolated from the
fruiting bodies of Ganoderma theaecolum. Chemical structures were elucidated on
the basis of spectroscopic evidence, including 1D, 2D NMR, mass spectrometric
data and circular dichroism spectra. Compounds 1, 4, 5, 8, 9 and 10 (10 MUM)
exhibited hepatoprotective activities against DL-galactosamine-induced cell
damage in HL-7702 cells.
PMID- 25111011
TI - Chemical investigation of the medicinal and ornamental plant Angelonia
angustifolia Benth. reveals therapeutic quantities of lupeol.
AB - Angelonia angustifolia Benth. is a small herbaceous plant with documented use as
an anti-inflammatory remedy by indigenous cultures in Latin America. It has
subsequently been developed as an ornamental annual widely available in nurseries
in the United States. Chemical investigation led to the discovery that lupeol is
the major organic soluble constituent in the roots, and is present in large
quantities in the aerial structures of the plant. Lupeol was identified by 1D and
2D NMR spectroscopic techniques and quantified by HPLC-MS. The concentration of
lupeol (9.14 mg/g in roots) in A. angustifolia is approximately 3 times higher
than any previously reported sources. Therefore, the amount of lupeol in the
roots of a single individual of A. angustifolia greatly exceeds the previously
determined topical threshold for significant reduction of inflammation. The
presence of topically therapeutic levels of lupeol in A. angustifolia provides
chemical rationale for its indigenous use. In addition, the established
cultivation of A. angustifolia could allow this plant to be used as a source of
the important bioactive molecule lupeol, or to be developed as a nutraceutical
without damaging wild populations.
PMID- 25111013
TI - Health-related quality of life of adolescent and young adult survivors of
childhood brain tumors.
AB - OBJECTIVE: Our aim was to expand research on predictors of health-related quality
of life (HRQOL) for adolescent and young adult survivors of childhood brain
tumors who are not living independently by evaluating the mediating role of
family functioning in the association of disease severity/treatment late effects
with survivor self-report and caregiver-proxy report of physical and emotional
HRQOL. METHODS: Mothers (N = 186) and their survivors living at home (N = 126)
completed self-report and caregiver-proxy report of physical and emotional HRQOL.
Mothers completed family functioning measures of general family functioning,
caregiving demands, and caregiver distress. Medical file review and caregiver
report were used to evaluate disease severity/treatment late effects. RESULTS:
Using structural equation models, family functioning was adjusted for
sociodemographic factors. Disease severity/treatment late effects had significant
direct effects on self-report and caregiver-proxy report of physical and
emotional HRQOL. Family functioning had a significant direct effect on caregiver
proxy report of physical and emotional HRQOL, but these findings were not
confirmed for self-report HRQOL. Model-fit indices suggested good fit of the
models, but the mediation effect of family functioning was not supported.
CONCLUSIONS: Disease severity/treatment late effects explained self-report and
caregiver-proxy report of physical and emotional HRQOL for these adolescent and
young adult survivors of childhood brain tumors. Family functioning was
implicated as an important factor for caregiver-proxy report only. To enhance
physical and emotional HRQOL, findings underscore the importance of coordinated,
multidisciplinary follow-up care for the survivors who are not living
independently and their families to address treatment late effects and support
family management.
PMID- 25111014
TI - Chimeric recombinant antibody fragments in cardiac troponin I immunoassay.
AB - OBJECTIVES: To introduce a novel nanoparticle-based immunoassay for cardiac
troponin I (cTnI) utilizing chimeric antibody fragments and to demonstrate that
removal of antibody Fc-part and antibody chimerization decrease matrix related
interferences. DESIGN AND METHODS: A sandwich-type immunoassay for cTnI based on
recombinant chimeric (mouse variable/human constant) antigen binding (cFab)
antibodies and intrinsically fluorescent nanoparticles was developed. To test
whether using chimeric antibody fragments helps to avoid matrix related
interferences, samples (n=39) with known amounts of triglycerides, bilirubin,
rheumatoid factor (RF) or human anti-mouse antibodies (HAMAs) were measured with
the novel assay, along with a previously published nanoparticle-based research
assay with the same antibody epitopes. RESULTS: The limit of detection (LoD) was
3.30ng/L. Within-laboratory precision for 29ng/L and 2819ng/L cTnI were 13.7% and
15.9%, respectively. Regression analysis with Siemens ADVIA Centaur(r) yielded a
slope (95% confidence intervals) of 0.18 (0.17-1.19) and a y-intercept of 1.94 (
1.28-3.91) ng/L. When compared to a previously published nanoparticle-based
assay, the novel assay showed substantially reduced interference in the tested
interference prone samples, 15.4 vs. 51.3%. A rheumatoid factor containing sample
was decreased from 241ng/L to =17),
but risks were also increased for some T-cell lymphomas (SIRs = 3.6-14.2),
marginal zone lymphoma (SIR = 2.4), lymphoplasmacytic lymphoma/Waldenstrom
macroglobulinemia (SIR = 3.6), and acute lymphoblastic leukemia/lymphoma (SIR =
2.4). CONCLUSION: HIV-infected people in the HAART era continue to have elevated
risk of AIDS-defining NHL subtypes, highlighting the contribution of moderate and
severe immunosuppression to their cause. Whereas non-AIDS-defining subtypes are
much less common, immunosuppression or other dysregulated immune states likely
play a role in the cause of some T-cell lymphomas, marginal zone lymphoma,
lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia, and acute lymphoblastic
leukemia/lymphoma.
PMID- 25111082
TI - Efficacy of prolonged tenofovir therapy on hepatitis delta in HIV-infected
patients.
AB - BACKGROUND: Hepatitis delta virus (HDV) produces the most severe form of chronic
viral hepatitis. We explored whether prolonged tenofovir exposure might be
beneficial on hepatitis delta in HIV-infected patients. METHODS: All HIV-infected
patients with hepatitis delta followed at our institution since year 2000 were
retrospectively examined. Serum HBV-DNA and HDV-RNA were quantified using
commercial assays. Liver fibrosis was measured using elastometry. RESULTS: A
total of 19 HIV/delta patients were identified. All were viremic for HDV and 11
for HBV. After a median tenofovir exposure of 58 months, all had undetectable HBV
DNA and 10 (53%) had undetectable HDV-RNA. The median drop in HDV-RNA in the
remaining nine HDV viremic patients at the end of follow-up was 2.4 log
copies/ml. A reduction above 30% in liver stiffness occurred in six out 10 (60%)
patients who achieved undetectable HDV-RNA, whereas hepatic stiffness did not
change in the remaining HDV viremic patients (P = 0.03). Serum HBsAg
concentrations did not decline significantly, although HBsAg seroclearance
occurred in three patients, all of whom became negative for HDV-RNA. CONCLUSION:
Long-term exposure to tenofovir significantly reduced serum HDV-RNA apart from
completely suppressing HBV-DNA in HIV-infected patients with hepatitis delta.
This virological benefit is accompanied by significant improvements in liver
fibrosis.
PMID- 25111083
TI - Influence of hepatitis C virus coinfection on CD4+ T cells of HIV-infected
patients receiving HAART.
AB - OBJECTIVE: The effects of hepatitis C virus (HCV) coinfection on immune
homeostasis and immune restoration in treated HIV infection are not well
understood. METHODS: We studied 79 HIV-infected patients who had been receiving
HAART for more than 2 years and who had HIV viral load below 50 copies/ml. Four
patient groups were studied: HIV/HCV, CD4+ cells above 350/MUl; HIV/HCV, CD4
cells below 350/MUl; HIV/HCV, CD4 cells above 350/MUl; HIV/HCV, CD4+ cells below
350/MUl. Controls comprised 20 healthy volunteers. Naive, central memory,
effector memory, and terminal effector CD4+ T cells were enumerated. Naive
CD4CD31 T cells were counted as recent thymic emigrants (RTEs). Activation state
and ex-vivo apoptosis of CD4+ T cells, levels of liver enzymes, and aspartate
aminotransferase-to-platelet ratio index were evaluated. RESULTS: CD4+ T-cell
counts and the numbers of all circulating CD4 T-cell maturation subsets were
diminished in HIV infection; CD4+ T-cell activation and apoptosis were increased
in HIV infection, but none of these indices was affected by HCV coinfection. RTE
numbers were diminished in HIV infection, were inversely related to age, and were
increased in women and lower in HIV/HCV patients than in singly HIV-infected
patients. In coinfected patients, RTE numbers were inversely related to levels of
liver enzymes, but not to HCV viral load. CONCLUSION: Whereas we could find no
relationship between HCV infection and most indices of CD4+ T-cell homeostasis or
activation, CD4+ RTEs are diminished in the circulation of HCV coinfected persons
and appear to be related to indices of ongoing hepatic damage or inflammation.
PMID- 25111085
TI - Sex-specific differences in offspring personalities across the laying order in
magpies Pica pica.
AB - Maternal effects provide an important mechanism for mothers to create variation
in offspring personality, and to potentially influence offspring life history
strategies e.g. creating more/less dispersive phenotypes. However, within-clutch
maternal effects often vary and hence there is potential for within-clutch
variation in personality. We studied the effects of hatching order on explorative
and neophobic behaviour of the magpies Pica pica in relation to sex using novel
environment and novel object experiments. Hatching order did affect explorative
behaviour in magpie, but did so in opposite directions for either sex. First
hatched females were more explorative and had a tendency to be less neophobic,
whereas in males, the reverse was true. Our results suggest that hormonal as well
as post-natal environmental mechanisms could be underpinning this pattern. Future
research is needed to fully understand the importance of both in creating
different offspring personalities. This article is part of a Special Issue
entitled: insert SI title.
PMID- 25111086
TI - Validated HPLC method for simultaneous estimation of khellol glucoside, khellin
and visnagin in Ammi visnaga L. fruits and pharmaceutical preparations.
AB - Tea bags including fruits of Ammi visnaga L. are used in Egypt as remedy for the
treatment of kidney stones. Our study focuses on developing simple and rapid
method utilising HPLC for quantitative estimation of khellol glucoside (KG),
khellin (KH) and visnagin (VS) simultaneously. Their concentrations were
determined in A. visnaga L. fruits at different developmental stages and in
pharmaceutical formulations together with following up them during shelf life.
Separation was accomplished using HPLC. Perfect resolution between KG, KH and VS
was possible through using a mobile phase consisting of
water:methanol:tetrahydrofuran (50:45:5, v/v/v). Peaks were detected at 245 nm.
The suggested method for the determination of KG, KH and VS was successful in
determining the analytes of interest without any interference of other compounds
and matrix. All validation parameters were satisfactory and the procedure was
relatively easy and fast as extracts are evaluated without previous steps of
purification.
PMID- 25111084
TI - The proteome of cholesteryl-ester-enriched versus triacylglycerol-enriched lipid
droplets.
AB - Within cells, lipids are stored in the form of lipid droplets (LDs), consisting
of a neutral lipid core, surrounded by a phospholipid monolayer and an outer
layer of protein. LDs typically accumulate either triacylglycerol (TAG) and
diacylglycerol or cholesteryl ester (CE), depending on the type of tissue.
Recently, there has been an increased interest in the proteins that surround LDs.
LD proteins have been found to be quite diverse, from structural proteins to
metabolic enzymes, proteins involved in vesicular transport, and proteins that
may play a role in LD formation. Previous proteomics analyses have focused on TAG
enriched LDs, whereas CE-enriched LDs have been largely ignored. Our study has
compared the LD proteins from CE-enriched LDs to TAG-enriched LDs in
steroidogenic cells. In primary rat granulosa cells loaded with either HDL to
produce CE-enriched LDs or fatty acids to produce TAG-enriched LDs, 61 proteins
were found to be elevated in CE-enriched LDs and 40 proteins elevated in TAG
enriched LDs with 278 proteins in similar amounts. Protein expression was further
validated by selected reaction monitoring (SRM) mass spectrometry (MS). SRM
verified expression of 25 of 27 peptides that were previously detected by tandem
mass tagging MS. Several proteins were confirmed to be elevated in CE-enriched
LDs by SRM including the intermediate filament vimentin. This study is the first
to compare the proteins found on CE-enriched LDs with TAG-enriched LDs and
constitutes the first step in creating a better understanding of the proteins
found on CE-enriched LDs in steroidogenic cells.
PMID- 25111087
TI - Design of functional nanoparticles and assemblies for theranostic applications.
AB - Nanostructured materials have found increasing applications in medical therapies
and diagnostics (theranostics). The main challenge is the ability to impart the
nanomaterials with structurally tailored functional properties which can
effectively target biomolecules but also provide signatures for effective
detection. The harnessing of functional nanoparticles and assemblies serves as a
powerful strategy for the creation of the structurally tailored multifunctional
properties. This article highlights some of the important design strategies in
recent investigation of metals (especially gold and silver), and magnetically
functionalized nanoparticles, and molecularly assembled or biomolecularly
conjugated nanoparticles with tunable optical, spectroscopic, magnetic, and
electrical properties for applications in several areas of potential theranostic
interests. Examples include colorimetric detection of amino acids and small
peptides, surface-enhanced Raman scattering detection of biomolecular recognition
of proteins and DNAs, delivery in cell transfection and bacteria inactivation,
and chemiresistive detection of breath biomarkers. A major emphasis is placed on
understanding how the control of the nanostructures and the molecular and
biomolecular interactions impact these biofunctional properties, which has
important implications for bottom-up designs of theranostic materials.
PMID- 25111088
TI - Effect of hydroxyapatite nanoparticles on osmotic responses of pig iliac
endothelial cells.
AB - In order to fully explore the potential applications of nanoparticles in
biopreservation, it is necessary to study the effect of nanoparticles on cell
membrane permeabilities. The aim of this study is therefore to comparatively
evaluate the osmotic responses of pig iliac endothelial cells in the absence and
presence of commercially available hydroxyapatite nanoparticles. The results
indicate that, after the introduction of 0.0 1 wt% hydroxyapatite nanoparticles,
the dependence of cell membrane hydraulic conductivity (Lp) on temperature still
obeys the Arrhenius relationship, while the reference value of the hydraulic
conductivity of the cell membrane at 273.15K (Lpg) and the activation energy for
water transport across cell membrane (ELp) change from 0.77 * 10(-14)m/Pa/s and
15.65 kJ/mol to 0.65 * 10(-14)m/Pa/s and 26.14 kJ/mol. That is to say, the
reference value of the hydraulic conductivity of the cell membrane has been
slightly decreased while the activation energy for water transport across cell
membrane has been greatly enhanced, and thus it implies that the hydraulic
conductivity of cell membrane are more sensitive to temperature in the presence
of nanoparticles. These findings are of potential significance to the
optimization of nanoparticles-aided cryopreservation.
PMID- 25111089
TI - Design and computational characterization of non-fullerene acceptors for use in
solution-processable solar cells.
AB - In an effort to seek high-performance small molecule electron acceptor materials
for use in heterojunction solar cells, computational chemistry was used to
examine a variety of terminal acceptor-conjugated bridge-core acceptor-conjugated
bridge-terminal acceptor small molecules. In particular, we have systematically
predicted the geometric, electronic, and optical properties of 16 potential small
molecule acceptors based upon a series of electron deficient pi-conjugated
building blocks that have been incorporated into materials exhibiting good
electron transport properties. Results show that the band gap, HOMO/LUMO energy
levels, orbital spatial distribution, and intrinsic dipole moments can be
systematically altered by varying the electron properties of the terminal or core
acceptor units. In addition, the identity of the conjugated bridge can help fine
tune the electronic properties of the molecule, where this study showed that the
strongest electron affinity of the conjugated pi-bridge increased the stability
in the HOMO and LUMO energies and increased the band gap of these small-molecule
acceptors. As a result, this work points toward an isoindigo (C5) core combined
with C2-thienopyrrole dione (A5) terminal units as the most promising small
molecule acceptor material that can be fine-tuned with the choice of conjugated
bridge and may be considered as reasonable candidates for synthesis and
incorporation into organic solar cells.
PMID- 25111090
TI - Comparing criterion- and trait-based personality disorder diagnoses in DSM-5.
AB - In the recent Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the
official personality disorder (PD) classification system remains unchanged.
However, DSM-5 also includes an alternative hybrid categorical-dimensional PD
system in Section III to spur additional research. One defining feature of the
alternative system is the incorporation of a trait model with PD-specific trait
configurations, but relatively little work has evaluated how these traits map
onto official PD diagnoses or their implications for diagnosis rates. To that
end, we compared official PD criteria to Section III PD traits in a sample of
current or recent psychiatric patients. We (a) evaluated the extent to which PD
traits predicted traditional PD criterion counts, and (b) computed trait-based
diagnosis rates and compared them to those reported in several published
outpatient and epidemiological samples. Overall, PD traits generally predicted PD
criterion counts, but with less than ideal specificity. In addition, we
identified differences in diagnosis rates across approaches. These results
provide some support for the Section III approach, but they also identify
important areas in need of refinement and future study before the field could
reasonably switch to a hybrid PD classification approach like that in Section
III.
PMID- 25111091
TI - The early access to medicines scheme.
PMID- 25111092
TI - Guidance on multi-morbidity: the challenge facing NICE.
PMID- 25111094
TI - Vasculitis: an update.
AB - The systemic vasculitides are uncommon but serious diseases. Early recognition
can be difficult because they mimic many conditions. Aggressive immunosuppression
is toxic but effective; a targeted approach with biological agents may improve
the outcome.
PMID- 25111095
TI - Biologics in systemic lupus erythematosus: current options and future
perspectives.
AB - Data from clinical trials highlighted the potential and pitfalls of the use of
biologics to treat systemic lupus erythematosus. With improved understanding of
immunopathogenesis and lessons learned from controlled trials, there is a growing
optimism for personalized treatment from an increasing range of targeted
therapies.
PMID- 25111096
TI - Biologics in rheumatoid arthritis: where are we going?
AB - Biological disease-modifying antirheumatic drugs have significantly improved
outcomes for patients with rheumatoid arthritis, but cost limits their use. This
article assesses data on patients who have achieved remission or low disease
activity with these drugs and the possibility of dose reduction or
discontinuation in these patients.
PMID- 25111097
TI - Why can't my child see 3D television?
AB - A child encountering difficulty in watching three-dimensional (3D) stereoscopic
displays could have an underlying ocular disorder. It is therefore valuable to
understand the differential diagnoses and so conduct an appropriate clinical
assessment to address concerns about poor 3D vision.
PMID- 25111098
TI - Effective medical leadership development for a complex NHS.
AB - The NHS Leadership Academy in England is investing L46 million in a standardized
model of development, with academic qualifications becoming essential in future
NHS leadership roles. This represents a cul-de-sac for medical leaders because it
is based on a series of misplaced assumptions about health-care leadership and
its development.
PMID- 25111099
TI - How competent do graduates feel to undertake the skills required by the General
Medical Council?
AB - The General Medical Council outlines the skills medical students are meant to
learn as undergraduates. This article summarizes how competent some foundation
year one doctors from one deanery felt to undertake these skills, what had
prepared them and what they would like more training on.
PMID- 25111100
TI - Isolated myeloid sarcoma of the buccal region.
PMID- 25111101
TI - Diogenes syndrome causing life-threatening complications of Paget's disease.
PMID- 25111102
TI - Recurrent sinusitis: think granulomatosis with polyangiitis.
PMID- 25111103
TI - Digestive enzyme supplements: replacement therapy for individuals unwilling to
take porcine products.
PMID- 25111104
TI - The outbreak of the first world war and the medical profession.
PMID- 25111106
TI - Should the national early warning score be adopted throughout the NHS?
PMID- 25111107
TI - In situ electrodeposition of an asymmetric sol-gel membrane based on an
octadecyltrimethoxysilane Langmuir film.
AB - The unique properties of Langmuir film formation were utilized in assembling a
thin skin of an asymmetric membrane. An octadecyltrimethoxysilane (ODTMS)
Langmuir monolayer was formed at the air-water interface and served as the
substrate for growing a bulky sol-gel polymer in situ. The latter was based on
the electrochemical deposition of tetramethoxysilane dissolved in the water
subphase by means of horizontal touch electrochemistry. The resultant asymmetric
layer that consisted of a thin hydrophobic ODTMS Langmuir film connected to a
bulk hydrophilic sol-gel network was studied in situ and ex situ by using various
techniques, such as cyclic voltammetry, electrochemical impedance spectroscopy
(EIS), scanning electron microscopy, transmission electron microscopy (TEM), and
goniometry. We found that a porous hydrophilic film grew on top of a hydrophobic
layer as was evident from TEM, contact angle, and EIS analyses. The film
thickness and film permeability could be controlled by changing the deposition
conditions such as the potential window applied and its duration. Hence, this
method offers an alternative approach for assembling asymmetric films for various
applications.
PMID- 25111108
TI - The association between prenatal sleep quality and obstetric outcome.
AB - BACKGROUND: Pregnancy-associated sleep disorder is a new category on the latest
version of the International Classification of Sleep Disorders. It is a
significant problem for pregnant women. PURPOSE: The present follow-up study
assesses the association between sleep quality during the second and third
trimesters of pregnancy and obstetric-neonatal outcomes. METHODS: A prospective
follow-up study design was used. Follow-up examination of the obstetric birth
records in the immediate postpartum period were carried out on 128 second
trimester and 120 third-trimester women and their newborns in two hospitals in
Taiwan. Poor sleep quality was identified using the Pittsburgh Sleep Quality
Index. Data were collected from October 2007 to June 2008. RESULTS: The
prevalence of poor sleepers (Pittsburgh Sleep Quality Index score > 5) was 58%
for second-trimester participants and 66% for third-trimester participants;
participants who were unemployed reported a significantly higher prevalence of
poor sleep quality than those who were employed. Subsequent review of the
participant's obstetric birth records revealed that third-trimester poor sleepers
were more likely to have had a vacuum-assisted delivery. CONCLUSIONS/IMPLICATIONS
FOR PRACTICE: This study identified poor sleep quality during the third trimester
as a novel risk factor for vacuum-assisted delivery. We suggest that prenatal
healthcare providers focus greater attention to the sleep disturbance condition
of pregnant women and provide proactive sleep counseling to facilitate pregnant
women's adjustment to the new psychosocial and physiological demands of
motherhood.
PMID- 25111109
TI - The effect of yoga exercise on improving depression, anxiety, and fatigue in
women with breast cancer: a randomized controlled trial.
AB - BACKGROUND: Depression, anxiety, and fatigue are among the most significant
problems that influence the quality of life of patients with breast cancer who
receive adjuvant chemotherapy. Although evidence has shown yoga to decrease
anxiety, depression, and fatigue in patients with cancer, few studies on the
effects of yoga have targeted patients with breast cancer. Yoga interventions
should be tested to promote the psychological and physical health of women with
breast cancer. PURPOSE: This study examines the effectiveness of an 8-week yoga
exercise program in promoting the psychological and physical health of women with
breast cancer undergoing adjuvant chemotherapy in terms of depression, anxiety,
and fatigue. METHODS: A sample of 60 women with nonmetastatic breast cancer was
recruited. Participants were randomly assigned into either the experimental group
(n = 30) or the control group (n = 30). A 60-minute, twice-per-week yoga exercise
was implemented for 8 weeks as the intervention for the participants in the
experimental group. The control group received standard care only. RESULTS:
Analysis using the Johnson-Neyman procedure found that the yoga exercise reduced
overall fatigue and the interference of fatigue in everyday life for the
experimental group participants. Significant reductions were obtained after 4
weeks of intervention participation for those experimental group patients with
relatively low starting baseline values (baseline item mean value < 3.31 and
3.22, respectively) and after 8 weeks for most patients (approximately 75%) with
moderate starting baseline values (baseline item mean value < 7.30 and 5.34,
respectively). The 8-week intervention did not significantly improve the levels
of depression (F = 1.29, p > .05) or anxiety (F = 2.7, p > .05).
CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The 8-week yoga exercise program developed
in this study effectively reduced fatigue in patients with breast cancer but did
not reduce depression or anxiety. Oncology nurses should strengthen their
clinical health education and apply yoga to reduce the fatigue experienced by
patients with breast cancer who undergo adjuvant chemotherapy.
PMID- 25111110
TI - Factors affecting perceptions of family function in caregivers of children with
attention deficit hyperactivity disorders.
AB - BACKGROUND: Attention deficit and hyperactivity disorder (ADHD) is the most
common neurobehavioral disorder of childhood. ADHD has been shown to persist into
adulthood in 30%-70% of cases. The long-term and escalating nature of ADHD
creates an increasing burden on families because of the influence of
hyperactivity and impulsivity on academic achievement and social interaction.
There is a lack of information on factors influencing function in the families of
children with ADHD. PURPOSE: The purpose of this study was to test theoretically
derived relationships among family demographic characteristics; family factors
such as support, hardiness, and caregiver health; and family-functioning
outcomes. METHODS: This study used a cross-sectional study and structural
equation modeling approach. A self-report questionnaire collected information
from 122 caregivers on demographics, income, employment, and marital status data
as well as on personal health, family support, family hardiness, and family
function statuses as determined, respectively, using the Duke Health Profile,
Family APGAR score, Family Hardiness Index, and Family Assessment Device.
RESULTS: Structural equation modeling provided a reasonable fit to the data using
AMOS (chi = .249, df = 1, p = .613, minimum discrepancy C = .249), goodness-of
fit index (.999), adjusted goodness of fit index (.990), normed fit index (.999),
comparative fit index (1.0), and root mean square error of approximation (.000).
Results indicated a 55.6% probability of becoming the construct model, with
family hardiness and family support directly affecting family function and
caregiver health. Family support functioned as a mediator in the relationship
between family hardiness and family function. CONCLUSIONS/IMPLICATIONS FOR
PRACTICE: The findings of this study help nurses improve professional assessments
and interventions for families of children with ADHD by highlighting the
importance of increased family support, promoting family hardiness, and promoting
caregivers' health to improved family function.
PMID- 25111111
TI - Exploring the relationship between personality features and teaching self
efficacy in clinical nursing preceptors.
AB - BACKGROUND: The clinical nursing preceptor system, first introduced in the 1960s,
is a one-on-one education and practice model. Preceptorship programs assign
experienced registered nurses (preceptors) as mentors or role models for new
clinical nurses (preceptees). PURPOSE: The objective of this study was to
delineate the relationship between personality features and teaching self
efficacy in clinical nursing preceptors. METHODS: In June 2009, clinical nursing
preceptors at a county hospital in Taiwan were asked to complete three
questionnaires, including (a) background demographics, (b) Eysenck Personality
Questionnaire, and (c) the teaching self-efficacy evaluation. A generalized
linear model was applied to determine the associations between the six dimensions
of teaching self-efficacy (maturity, teaching self-efficacy beliefs, professional
skill, teaching strategy effectiveness, quality of interpersonal relationships,
and objective teaching evaluation) and four dimensions related to personality
features (extraversion, neuroticism, psychoticism, and the lie scale), adjusted
for baseline characteristics. RESULTS: One hundred sixteen nurse preceptors (mean
age = 31.2 years, range = 25-54 years) participated in this survey. Analysis
showed that extraversion was related to higher scores for maturity, teaching self
efficacy beliefs, professional skill, teaching strategy effectiveness, and
objective teaching evaluation. A higher neuroticism score was negatively
associated with maturity. The psychoticism score had no significant associations.
A higher score on the lie scale was related to lower professional skill and less
teaching strategy effectiveness. CONCLUSIONS/IMPLICATIONS FOR PRACTICE:
Personality features relate significantly to teaching self-efficacy in nursing
preceptors. This study identified personality features that may influence the
success of nurses in becoming competent clinical preceptors.
PMID- 25111112
TI - A rehabilitation program for Alzheimer's disease.
AB - BACKGROUND: We present the design and implementation of a rehabilitation program
(RP) adapted for people diagnosed with various phases of Alzheimer's disease
(AD). The RP is a cognitive stimulation program that integrates the
recommendations of the American College of Sports Medicine for aerobic,
resistance, and balance exercises. PURPOSE: The aim of this study is to evaluate
the effect of the RP on the physical and functional capacities, cognitive
functions, and quality of life (QOL) of patients with AD. METHODS: We enrolled 64
participants with AD for an RP intervention lasting 12 months. The research used
a quasiexperimental approach. Assessed variables included cognitive ability (Mini
Mental State Examination), fitness (Chair Stand Test), level of independence
(Barthel Index), and QOL (the 12-item Short Form Health Survey). Statistical
analyses used the Student's t test, Mann-Whitney U test, and the chi-squared
test. The statistical significance level was set at 5%. RESULTS: The results
indicate the effectiveness of the RP in improving the physical fitness and the
QOL of participants with mild- to moderate-phase AD. CONCLUSIONS/IMPLICATIONS FOR
PRACTICE: The RP has a positive effect on patients with mild- to moderate-phase
AD. However, we identified no effect for the RP on cognitive ability. These
findings provide empirical evidence to support the use of RP as an effective
complementary therapy. Improving the physical capacity and the QOL may have
important long-term benefits for the older adults and their caregivers. The
results of this study should be helpful to decision makers and geriatric health
centers in planning and implementing RPs for elderly people with AD.
PMID- 25111113
TI - Work-family conflict and job performance in nurses: the moderating effects of
social support.
AB - BACKGROUND: A large number of women are employed in the labor market. This
phenomenon has widely supplanted the traditional family model of full-time
working fathers and full-time housewives with the dual-income family model. Most
nurses have both family and work responsibilities and hope to balance these two
aspects of their lives. Work-family conflict (WFC) is thus a significant issue
faced by professional nurses. PURPOSES: This study examines the relationship
between WFC and job performance in the nursing context and explores the
moderating effects of different sources of social support. METHODS: This study
questionnaire used a self-reporting scale. To avoid common method variance,
research data were collected at two time points. Five hundred twenty
questionnaires were sent to nurses working at five hospitals in Taiwan, and 501
were returned, of which 495 were valid and used in analysis. Hierarchical
regression analysis was used to test study hypotheses. RESULTS: Study findings
were (a) degree of family-to-work conflict influenced job performance negatively,
(b) level of WFC did not significantly affect job performance, (c) support from
friends strengthened the negative effect of family-to-work conflict on job
performance, and (d) support from coworkers weakened the relationship between WFC
and job performance. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: It is hoped that the
findings of this study will be useful for nursing managers, organizations, and
future research. Hospital organizations and nursing departments have a positive
role to play in fostering an organizational culture that helps its staffs balance
work and family responsibilities. A strategy of human resource management that is
consistent with the demands of nurses may help reduce WFC.
PMID- 25111114
TI - The link of sexual sensation seeking to acceptance of cybersex, multiple sexual
partners, and one-night stands among Taiwanese college students.
AB - BACKGROUND: Young people in Taiwan have become more liberal and active toward
sex. Despite heavy investments of money, time, and effort, sexual education
programs have generally lagged expectations. PURPOSE: Personality traits such as
sexual sensation seeking are found to be significantly associated with risky
sexual behaviors. This study, therefore, attempts to explore the link of sexual
sensation seeking to acceptance by Taiwanese college students of cybersex,
multiple sexual partners, and one-night stands. METHODS: A cross-sectional study
was conducted using the multistage cluster sampling method. Five hundred sixteen
students recruited from eight universities/colleges in Taiwan participated in
this study, and 507 completed the self-report questionnaire. The valid response
rate was 98.26%. RESULTS: The results reveal that high-sexual-sensation seekers
were more likely than low-sexual-sensation seekers to accept cybersex, multiple
sexual partners, and one-night stands. CONCLUSIONS/IMPLICATIONS FOR PRACTICE:
This study suggests that the designers of campus-based health prevention
campaigns should target campaign messages on high-sexual-sensation seekers using
novel, thrilling, and complex messages to achieve safe sex educational campaign
goals.
PMID- 25111115
TI - Do randomized controlled nursing trials have a pragmatic or explanatory attitude?
Findings from the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) tool
exercise.
AB - BACKGROUND: Randomized controlled trials (RCTs) may be categorized as either
effectiveness trials or efficacy trials, which may be categorized by the
Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) tool. However, no data
regarding the application of the PRECIS tool in a cluster of RCTs belonging to a
specific discipline such as nursing are available. PURPOSE: The principal aim of
this study was to assess the prevailing nature (pragmatic vs. explanatory) of a
cluster of clinical nursing RCTs. Evaluating the suitability of the PRECIS in the
analysis of nursing RCTs was the secondary aim. METHODS: All nursing RCTs
published in 2010 were identified through a systematic review and extracted in
full-text form. An explanatory-pragmatic (E-P) group consisting of 11 researchers
trained in the use of the PRECIS tool evaluated each RCT in terms of 10 domains,
respectively scored on a scale ranging from 5 (pragmatic) to 1 (explanatory). The
E-P group further scored the feasibility of the PRECIS tool using a numerical
rating scale (0 = not at all, 10 = entirely feasible). RESULTS: Along the
pragmatic-explanatory continuum, assuming 50 as the highest degree of pragmatism
and 10 as the highest degree of explanatory, the evaluation of nursing RCTs
returned an average of 31.1 (median = 31, SD = 7.18, range = 13-44). On the
pragmatic-explanatory continuum, the evaluated nursing RCTs tended to be
pragmatic, which seems to be consistent with the purposes of the nursing
discipline. The feasibility of the PRECIS tool in the evaluation of nursing
trials as perceived by the E-P Group was, on average, 7.09 (SD = 1.09, 95% CI
[6.35, 7.82]). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Applying the PRECIS tool is
perceived to be highly feasible in the critical appraisal of a cluster of RCTs in
a specific discipline such as nursing.
PMID- 25111116
TI - Trp28Arg/Ile35Thr LHB gene variants are associated with elevated testosterone
levels in women with polycystic ovary syndrome.
AB - INTRODUCTION: Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder,
of multifactorial etiology, which affects 6-10% of women of reproductive age. It
is considered the leading cause of anovulatory infertility, menstrual disorders
and hyperandrogenism in this population. The genetic basis of PCOS is still
largely unknown despite significant family clustering; determining its mode of
inheritance is particularly difficult given the heterogenic presentation of the
disease. MATERIALS AND METHODS: 130 Brazilian women, aged 14-42 years, who met
the 2003 Rotterdam criteria for PCOS diagnosis, were included, and 96 healthy
women constituted the control group. Presence of hirsutism was classified using
the modified Ferriman-Gallwey score (F-G score) as absent (<=7), mild (8-14), and
severe (>=15). Blood levels of luteinizing hormone (LH), total testosterone (TT),
dehydroepiandrosterone sulfate (DHEA-S) and androstenedione were determined. The
coding region of the luteinizing hormone beta-subunit (LHB) gene was amplified
and sequenced. Differences in allelic and genotypic frequency distribution of
each polymorphism across controls and cases were estimated by the Mantel-Haenszel
chi-square or Fisher's exact test (p<0.05), and the probability of an association
between the detection of a polymorphism and presence of a diagnosis of PCOS, by
logistic regression. RESULT(S): Sequencing detected 8 polymorphisms in the LHB
gene coding region. Two polymorphisms in linkage disequilibrium were
significantly more prevalent in the presence of hyperandrogenemia:
rs1800447/rs34349826 (Trp28Arg/Ile35Thr) (p=0.02). CONCLUSION(S): In this series,
a modulatory effect of LHB polymorphisms on hyperandrogenemia phenotype of PCOS
was observed; however, this finding needs to be replicated in other populations.
PMID- 25111117
TI - In-silico identification and characterization of organic and inorganic chemical
stress responding genes in yeast (Saccharomyces cerevisiae).
AB - To study the life processes of all eukaryotes, yeast (Saccharomyces cerevisiae)
is a significant model organism. It is also one of the best models to study the
responses of genes at transcriptional level. In a living organism, gene
expression is changed by chemical stresses. The genes that give response to
chemical stresses will provide good source for the strategies in engineering and
formulating mechanisms which are chemical stress resistant in the eukaryotic
organisms. The data available through microarray under the chemical stresses like
lithium chloride, lactic acid, weak organic acids and tomatidine were studied by
using computational tools. Out of 9335 yeast genes, 388 chemical stress
responding genes were identified and characterized under different chemical
stresses. Some of these are: Enolases 1 and 2, heat shock protein-82, Yeast
Elongation Factor 3, Beta Glucanase Protein, Histone H2A1 and Histone H2A2
Proteins, Benign Prostatic Hyperplasia, ras GTPase activating protein,
Establishes Silent Chromatin protein, Mei5 Protein, Nondisjunction Protein and
Specific Mitogen Activated Protein Kinase. Characterization of these genes was
also made on the basis of their molecular functions, biological processes and
cellular components.
PMID- 25111118
TI - Genotype-based databases for variants causing rare diseases.
AB - Inherited diseases are the result of DNA sequence changes. In recessive diseases,
the clinical phenotype results from the combined functional effects of variants
in both copies of the gene. In some diseases there is often considerable
variability of clinical presentation or disease severity, which may be predicted
by the genotype. Additional effects may be triggered by environmental factors, as
well as genetic modifiers which could be nucleotide polymorphisms in related
genes, e.g. maternal ApoE or ABCA1 genotypes which may have an influence on the
phenotype of SLOS individuals. Here we report the establishment of genotype
variation databases for various rare diseases which provide individual clinical
phenotypes associated with genotypes and include data about possible genetic
modifiers. These databases aim to be an easy public access to information on rare
and private variants with clinical data, which will facilitate the interpretation
of genetic variants. The created databases include ACAD8 (isobutyryl-CoA
dehydrogenase deficiency (IBD)), ACADSB (short-chain acyl-CoA dehydrogenase
(SCAD) deficiency), AUH (3-methylglutaconic aciduria (3-MGCA)), DHCR7 (Smith
Lemli-Opitz syndrome), HMGCS2 (3-hydroxy-3-methylglutaryl-CoA synthase 2
deficiency), HSD17B10 (17-beta-hydroxysteroid dehydrogenase X deficiency), FKBP14
(Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing
loss; EDSKMH) and ROGDI (Kohlschutter-Tonz syndrome). These genes have been
selected because of our specific research interests in these rare and metabolic
diseases. The aim of the database was to include all identified individuals with
variants in these specific genes. Identical genotypes are listed multiple times
if they were found in several patients, phenotypic descriptions and biochemical
data are included as detailed as possible in view also of validating the proposed
pathogenicity of these genotypes. For DHCR7 genetic modifier data (maternal APOE
and ABCA1 genotypes) is also included. Databases are available at
http://databases.lovd.nl/shared/genes and will be updated based on periodic
literature reviews and submitted reports.
PMID- 25111119
TI - Preparation and in vitro-in vivo evaluation of ofloxacin loaded ophthalmic nano
structured lipid carriers modified with chitosan oligosaccharide lactate for the
treatment of bacterial keratitis.
AB - The objective of this study was to explore the potential of the nanostructured
lipid carriers (NLCs) modified with chitosan oligosaccharide lactate (COL) for
topical ocular application. Ofloxacin (OFX) loaded NLCs were prepared by
microemulsion or high shear homogenization methods. For combination of NLCs
Compritol HD5 ATO was used as solid lipid, oleic acid as liquid lipid, Tween 80
as surfactant, ethanol as co-surfactant. The optimum NLCs was modified with 0.75%
COL. The properties of NLCs in the absence or presence of OFX (0.3%) were
characterized as zeta potential, particle size, viscosity and pH, TEM, drug
loading, encapsulation efficiency and anti-microbial properties. Ex-vivo
penetration/permeation studies were performed with rabbit cornea in Franz
diffusion cells. The penetration rate of OFX from NM-COL4OFX and NH-COL4OFX were
significantly higher than commercial solution. Based on the selected
formulations, in vivo tests were carried out by eye-drop instillation of NLCs in
rabbit. The addition of COL improved the preocular residence time, controlled the
drug release and enhanced the corneal bioavailability. In conclusion, OFX COL
modified NLCs prepared by high shear homogenization method could be offered as a
promising strategy for ocular drug delivery.
PMID- 25111120
TI - Effects of information processing speed on learning, memory, and executive
functioning in people living with HIV/AIDS.
AB - INTRODUCTION: It is unclear whether or to what degree literacy, aging, and other
neurologic abnormalities relate to cognitive deficits among people living with
HIV/AIDS in the combined antiretroviral therapy (CART) era. The primary aim of
this study was to simultaneously examine the association of age, HIV-associated
motor abnormalities, major depressive disorder, and reading level with
information processing speed, learning, memory, and executive functions, and to
determine whether processing speed mediated any of the relationships between
cognitive and noncognitive variables. METHOD: Participants were 186 racially and
ethnically diverse men and women living with HIV/AIDS who underwent comprehensive
neurological, neuropsychological, and medical evaluations. Structural equation
modeling was utilized to assess the extent to which information processing speed
mediated the relationship between age, motor abnormalities, major depressive
disorder, and reading level with other cognitive abilities. RESULTS: Age, motor
dysfunction, reading level, and current major depressive disorder were all
significantly associated with information processing speed. Information
processing speed fully mediated the effects of age on learning, memory, and
executive functioning and partially mediated the effect of major depressive
disorder on learning and memory. The effect of motor dysfunction on learning and
memory was fully mediated by processing speed. CONCLUSIONS: These findings
provide support for information processing speed as a primary deficit, which may
account, at least in part, for many of the other cognitive abnormalities
recognized in complex HIV/AIDS populations. The association of age and
information processing speed may account for HIV/aging synergies in the
generation of CART-era cognitive abnormalities.
PMID- 25111121
TI - The effects of fructose-containing sugars on weight, body composition and
cardiometabolic risk factors when consumed at up to the 90th percentile
population consumption level for fructose.
AB - The American Heart Association (AHA) and World Health Organization (WHO) have
recommended restricting calories from added sugars at lower levels than the
Institute of Medicine (IOM) recommendations, which are incorporated in the
Dietary Guidelines for Americans 2010 (DGAs 2010). Sucrose (SUC) and high
fructose corn syrup (HFCS) have been singled out for particular concern, because
of their fructose content, which has been specifically implicated for its
atherogenic potential and possible role in elevating blood pressure through uric
acid-mediated endothelial dysfunction. This study explored the effects when these
sugars are consumed at typical population levels up to the 90th percentile
population consumption level for fructose. Three hundred fifty five overweight or
obese individuals aged 20-60 years old were placed on a eucaloric diet for 10
weeks, which incorporated SUC- or HFCS-sweetened, low-fat milk at 8%, 18% or 30%
of calories. There was a slight change in body weight in the entire cohort (169.1
+/- 30.6 vs. 171.6 +/- 31.8 lbs, p < 0.01), a decrease in HDL (52.9 +/- 12.2 vs.
52.0 +/- 13.9 mg/dL, p < 0.05) and an increase in triglycerides (104.1 +/- 51.8
vs. 114.1 +/- 64.7 mg/dL, p < 0.001). However, total cholesterol (183.5 +/- 42.8
vs. 184.4 mg/dL, p > 0.05), LDL (110.3 +/- 32.0 vs. 110.5 +/- 38.9 mg/dL, p >
0.05), SBP (109.4 +/- 10.9 vs. 108.3 +/- 10.9 mmHg, p > 0.05) and DBP (72.1 +/-
8.0 vs. 71.3 +/- 8.0 mmHg, p > 0.05) were all unchanged. In no instance did the
amount or type of sugar consumed affect the response to the intervention
(interaction p > 0.05). These data suggest that: (1) when consumed as part of a
normal diet, common fructose-containing sugars do not raise blood pressure, even
when consumed at the 90th percentile population consumption level for fructose
(five times the upper level recommended by the AHA and three times the upper
level recommended by WHO); (2) changes in the lipid profile are mixed, but
modest.
PMID- 25111122
TI - Nutrient intake in Italian infants and toddlers from North and South Italy: the
Nutrintake 636 study.
AB - We performed a cross-sectional study to compare the intake of energy,
macronutrients, fiber, sodium and iron and the anthropometric status of infants
and toddlers living in North (Milano) and South Italy (Catania). Nutrient intake
was evaluated using a 7-day weighed food record. Out of 400 planned children aged
6 to 36 months, 390 (98%) were recruited, 189 in Milano and 201 in Catania. The
mean (standard deviation) age was 17 (9) months in Milano and 17 (10) months in
Catania. Anthropometry, energy intake and macronutrient intake were similar in
Milano and Catania. However, iron intake was 27% lower and fiber intake 16%
higher in Milano than in Catania. Despite normal anthropometry and energy intake,
in the pooled sample there was a high intake of proteins, simple carbohydrates,
saturated fats and sodium, and a low intake of iron and fiber compared to Italian
reference values. This is the first study to report the macro- and micro-nutrient
intake of children aged <12 months using the 7-day weighed food record and one of
the very few studies that have employed such reference method in children from
the general population.
PMID- 25111124
TI - Parasitic myoma in women after laparoscopic myomectomy: A late sequela of
morcellation?
PMID- 25111123
TI - Dietary fructose reduction improves markers of cardiovascular disease risk in
Hispanic-American adolescents with NAFLD.
AB - Nonalcoholic fatty liver disease (NAFLD) is now thought to be the most common
liver disease worldwide. Cardiovascular complications are a leading cause of
mortality in NAFLD. Fructose, a common nutrient in the westernized diet, has been
reported to be associated with increased cardiovascular risk, but its impact on
adolescents with NAFLD is not well understood. We designed a 4-week randomized,
controlled, double-blinded beverage intervention study. Twenty-four overweight
Hispanic-American adolescents who had hepatic fat >8% on imaging and who were
regular consumers of sweet beverages were enrolled and randomized to calorie
matched study-provided fructose only or glucose only beverages. After 4 weeks,
there was no significant change in hepatic fat or body weight in either group. In
the glucose beverage group there was significantly improved adipose insulin
sensitivity, high sensitivity C-reactive protein (hs-CRP), and low-density
lipoprotein (LDL) oxidation. These findings demonstrate that reduction of
fructose improves several important factors related to cardiovascular disease
despite a lack of measurable improvement in hepatic steatosis. Reducing dietary
fructose may be an effective intervention to blunt atherosclerosis progression
among NAFLD patients and should be evaluated in longer term clinical trials.
PMID- 25111127
TI - Dioscin inhibits colon tumor growth and tumor angiogenesis through regulating
VEGFR2 and AKT/MAPK signaling pathways.
AB - Dioscin has shown cytotoxicity against cancer cells, but its in vivo effects and
the mechanisms have not elucidated yet. The purpose of the current study was to
assess the antitumor effects and the molecular mechanisms of dioscin. We showed
that dioscin could inhibit tumor growth in vivo and has no toxicity at the test
condition. The growth suppression was accompanied by obvious blood vessel
decrease within solid tumors. We also found dioscin treatment inhibited the
proliferation of cancer and endothelial cell lines, and most sensitive to primary
cultured human umbilical vein endothelial cells (HUVECs). What's more, analysis
of HUVECs migration, invasion, and tube formation exhibited that dioscin has
significantly inhibitive effects to these actions. Further analysis of blood
vessel formation in the matrigel plugs indicated that dioscin could inhibit VEGF
induced blood vessel formation in vivo. We also identified that dioscin could
suppress the downstream protein kinases of VEGFR2, including Src, FAK, AKT and
Erk1/2, accompanied by the increase of phosphorylated P38MAPK. The results
potently suggest that dioscin may be a potential anticancer drug, which
efficiently inhibits angiogenesis induced by VEGFR2 signaling pathway as well as
AKT/MAPK pathways.
PMID- 25111129
TI - Crossover between entropic and interfacial elasticity and osmotic pressure in
uniform disordered emulsions.
AB - We develop a simple predictive model of the osmotic pressure Pi and linear shear
elastic modulus G of uniform disordered emulsions that includes energetic
contributions from entropy and interfacial deformation. This model yields a
smooth crossover between an entropically dominated G ~ kBT/a(3) for droplet
volume fractions phi below a jamming threshold for spheres, phic, and an
interfacially dominated G ~ sigma/a for phi above phic, where a and sigma are the
undeformed radius and interfacial tension, respectively, of a droplet and T is
the temperature. We show that this model reduces to the known phi-dependent
jamming behavior G(phi) ~ (sigma/a)phi(phi - phic) as T -> 0 for phi > phic of
disordered uniform emulsions, and it also produces the known divergence for
disordered hard spheres G(phi) ~ (kBT/a(3))phi/(phic - phi) for phi < phic when
sigma -> infinity. We compare predictions of this model to data for disordered
uniform microscale emulsion droplets, corrected for electrostatic repulsions. The
smooth crossover captures the observed trends in G and Pi below phic better than
existing analytic models of disordered emulsions, which do not make predictions
below phic. Moreover, the model predicts that entropic contributions to the shear
modulus can become more significant for nanoemulsions as compared to microscale
emulsions.
PMID- 25111128
TI - Is bisphenol S a safe substitute for bisphenol A in terms of metabolic function?
An in vitro study.
AB - As bisphenol A (BPA) has been shown to induce adverse effects on human health,
especially through the activation of endocrine pathways, it is about to be
withdrawn from the European market and replaced by analogues such as bisphenol S
(BPS). However, toxicological data on BPS is scarce, and so it is necessary to
evaluate the possible effects of this compound on human health. We compared the
effect of BPA and BPS on obesity and hepatic steatosis processes using low doses
in the same range as those found in the environment. Two in vitro models were
used, the adipose cell line 3T3-L1 and HepG2 cells, representative of hepatic
functions. We analyzed different parameters such as lipid and glucose uptakes,
lipolysis, leptin production and the modulation of genes involved in lipid
metabolism and energy balance. BPA and BPS induced an increase in the lipid
content in the 3T3-L1 cell line and more moderately in the hepatic cells. We also
observed a decrease in lipolysis after bisphenol treatment of adipocytes, but
only BPS was involved in the increase in glucose uptake and leptin production.
These latter effects could be linked to the modulation of SREBP-1c, PPARgamma,
aP2 and ERRalpha and gamma genes after exposure to BPA, whereas BPS seems to
target the PGC1alpha and the ERRgamma genes. The findings suggest that both BPA
and BPS could be involved in obesity and steatosis processes, but through two
different metabolic pathways.
PMID- 25111131
TI - Current issues of RNAi therapeutics delivery and development.
AB - 12 years following the discovery of the RNAi mechanism in Man, a number of RNAi
therapeutics development candidates have emerged with profiles suggesting that
they could become drugs of significant medical importance for diseases like TTR
amyloidosis, HBV, solid cancers, and hemophilia. Despite this robust progress,
the perception of RNAi therapeutics has been on a roller-coaster ride driven not
only by science, but also regulatory trends, the stock markets, and Big Pharma
business development decisions [1]. This presentation provides an update on the
current state of RNAi therapeutics development with a particular focus on what
RNAi delivery can achieve today and key challenges to be overcome to expand
therapeutic opportunities. The delivery of RNAi triggers to disease-relevant cell
types clearly represents the rate-limiting factor in broadly expanding the
applicability of RNAi therapeutics. Today, with at least 3 delivery options
(lipid nanoparticles/LNPs, GalNAc-siRNA conjugates, Dynamic PolyConjugates/DPCs)
for which profound gene knockdowns have been demonstrated in non-human primates
and in the clinic, RNAi therapeutics should in principle be able to address most
diseases related to gene expression in the liver. Given the central importance of
the liver in systemic physiology, this already represents a significant
therapeutic and commercial opportunity rivaling that of e.g. monoclonal
antibodies. Beyond the liver, there is a reason to believe that current RNAi
therapeutics technologies can address a number of solid tumors (e.g. LNPs),
diseases of the eye (e.g. self-delivering RNAi triggers) as well as diseases
involving the respiratory epithelium (e.g. aerosolized LNPs), certain phagocytic
cells (LNPs), hematopoietic stem cells and their progeny (lentiviral DNA-directed
RNAi), vascular endothelial cells (cationic lipoplexes), and certain cell types
in the kidney (self-delivering RNAi triggers, DPCs; Table 1). Despite this
success, there has been a sense that the applications of RNAi therapeutics are
rather limited. This is largely based on the observation that the biodistribution
of RNAi formulations is typically more limited compared to small molecules and
oral administration is not possible with current technologies. Similarly, the
utility of a given RNAi formulation is limited to a few cell types and tissues at
most and a universal delivery strategy should remain elusive for the foreseeable
future. Therefore, to further expand on the therapeutic utility and patient
convenience of RNAi, it is important to overcome a number of delivery-related
technical and scientific challenges which will be discussed in this presentation.
For systemic applications, these include the necessity for extended blood
circulation times, vascular escape (probably the most rewarding inquiry
currently), tissue penetration, cellular uptake, and escape into the cytoplasm.
In terms of safety, it is important that these formulations do not accumulate in
the body, do not cause excessive off-targeting due to 'chemical stickiness'
(often useful for purposes of biodistribution), and overcome the
physical/biological barriers in a controlled manner. The time for realizing the
therapeutic potential of RNAi has come. At the same time, it is important to lay
the foundations for the next leg of value creation by overcoming the challenges
of delivering RNAi to new cell types. Based on results from exploratory research,
the renewed interest in RNAi therapeutics and capital infusion, there is a reason
to be optimistic that this can be achieved.
PMID- 25111130
TI - Microparticle-loaded neonatal porcine Sertoli cells for cell-based therapeutic
and drug delivery system.
AB - Neonatal porcine Sertoli cells (NPSC) are immune privileged cells showing innate
phagocytic and antibacterial activities. NPSC have been shown capable of
immunoaltering the body's response and possess lung homing capacity. These
properties encourage investigation of NPSC as functional components of cell-based
therapeutic protocols to treat lung infections and related complications. In this
work, for the first time, NPSC were tailored to carry an antibiotic drug loaded
into poly(d,l lactic) acid microparticles (MP). A loading protocol was developed,
which afforded 30% drug uptake and high stability over time, with little or no
effects on NPSC viability, morphology, reactive oxygen species production and DNA
integrity. FSH receptor integrity, and TGFbeta (transforming growth factor beta)
and AMH (anti-Mullerian hormone) expressions were unchanged after 1month of
cryopreservation. Protein tyrosine kinase activation due to phagocytosis may have
had resulted in changes in inhibin B expression. The activity of MP-loaded or
NPSC alone against Pseudomonas aeruginosa was maintained throughout 1month of
storage. NPSC couple an innate antibacterial activity with the capacity to embody
drug loaded MP. We showed for the first time that engineered NPSC can be
cryopreserved with no loss of their basic properties, thereby possibly
representing a novel approach for cell-based therapeutic and drug delivery
system.
PMID- 25111132
TI - Origin of cardiovascular risk in overweight preschool children: a cohort study of
cardiometabolic risk factors at the onset of obesity.
AB - IMPORTANCE: To date, the relationship among adiposity, insulin resistance, and
cardiovascular risk factors at the onset of overweight or obesity has been
unexplored. OBJECTIVES: To assess whether insulin resistance and metabolic
abnormalities are detectable at the onset of obesity and to unravel the interplay
among adiposity, insulin resistance, and other such abnormalities. DESIGN,
SETTING, AND PARTICIPANTS: The Origin of Cardiovascular Risk in Overweight
Preschool Children cohort study aimed to evaluate at the onset of obesity in
preschool children the prevalence of metabolic abnormalities, including
hypertension, dyslipidemia, impaired carbohydrate metabolism, and nonalcoholic
fatty liver disease. Between July 1, 2011, and July 30, 2012, in the Rome
municipality, 13 family pediatricians enrolled healthy children (age range, 2.0
5.8 years) in the study during their routine practice of growth monitoring.
Clinical medical records of 5729 children were reviewed; 597 children manifested
new-onset overweight or obesity as their body mass index changed from normal
weight to overweight or obesity in the previous 12 months according to the
International Obesity Task Force classification. Of them, 219 were studied. MAIN
OUTCOMES AND MEASURES: Patients with new-onset overweight or obesity underwent
clinical laboratory testing, including oral glucose tolerance test, and
ultrasonographic investigations of fatty liver and intimal medial thickness of
the common carotid arteries, subcutaneous adipose tissue, and visceral adipose
tissue. The homeostatic assessment model algorithm-insulin resistance was
calculated. RESULTS: Among the entire population (n = 5729), overweight increased
from 7.0% at 2.0 years to 16.9% at 5.8 years, with corresponding figures of 1.1%
to 2.9% for obesity. In total, 597 overweight or obese children (10.4%) were
identified, and 219 of them (36.7%) were studied. Among the latter, 86 patients
(39.3%) had at least 1 metabolic abnormality. Hypertension was diagnosed in 29
patients (13.2%), dyslipidemia in 55 patients (25.1%), impaired fasting glucose
level in 7 patients (3.2%), and glucose intolerance in 6 patients (2.7%).
Nonalcoholic fatty liver disease was diagnosed in 68 patients (31.1%).
CONCLUSIONS AND RELEVANCE: Cardiometabolic risk factors, including fatty liver,
are detectable in preschoolers at the onset of overweight or obesity, despite
short-term exposure to excess weight and reduced insulin sensitivity. Our
findings suggest the need to screen for cardiometabolic abnormalities at an
earlier age than is now recommended.
PMID- 25111133
TI - New members of fluorescent 1,8-naphthyridine-based BF2 compounds: selective
binding of BF2 with terminal bidentate N^N^O and N^C^O groups and tunable
spectroscopy properties.
AB - Intensely luminescent 1,8-naphthyridine-BF2 complexes 1-9 containing terminal
bidentate N^N^O and/or N^C^O groups are synthesized and structurally
characterized by X-ray diffraction, electrospray ionization mass spectrometry,
(1)H and (19)F NMR spectroscopy and elemental analysis. Complexes 1-4 are
synthesized from 2-acetamino-1,8-naphthyridine derivatives by a facile route.
Selective bonding modes and the chemical stability of complexes 5 and 6 obtained
by reacting BF3.Et2O with 1,8-naphthyridine derivatives bearing dual-functional
groups (N^C^O and N^N^O) are investigated by crystal structure analysis and time
dependent density functional theory calculations. The products containing a BF2
core bound to a N^C^O chelating group are energetically favorable and can expand
the range of derivatives by substitution at the 2-position. In this regard, a
free -NH2 group at the 2-position of complex 7 obtained from 5 can be
functionalized under a variety of pH conditions to generate complexes 8 and 9,
which bear flexible coordination arms that can be used to recognize certain
transition metals. The photophysical properties of the complexes are examined in
solution and solid state at room temperature. Compared with those of the starting
naphthyridine-based compounds, the naphthyridine-BF2 complexes display desirable
light-absorbing properties and intense solution and solid-state emission with
large Stokes shifts. Complex 4 in solution exhibited an emission quantum yield of
0.98. In complexes 5-9, the binding sites for the BF2 core change from N^N^O to
N^C^O, which leads to red shifts of absorption and emission, excellent chemical
stability and high emission quantum yields.
PMID- 25111134
TI - Deterministic coupling of a single silicon-vacancy color center to a photonic
crystal cavity in diamond.
AB - Deterministic coupling of single solid-state emitters to nanocavities is the key
for integrated quantum information devices. We here fabricate a photonic crystal
cavity around a preselected single silicon-vacancy color center in diamond and
demonstrate modification of the emitters internal population dynamics and
radiative quantum efficiency. The controlled, room-temperature cavity coupling
gives rise to a resonant Purcell enhancement of the zero-phonon transition by a
factor of 19, coming along with a 2.5-fold reduction of the emitter's lifetime.
PMID- 25111135
TI - Radiofrequency ablation for the treatment of gastric antral vascular ectasia.
AB - BACKGROUND AND STUDY AIMS: The traditional endoscopic treatment for gastric
antral vascular ectasia (GAVE) is argon plasma coagulation, but results are not
always positive. Radiofrequency ablation (RFA) is a new endoscopic therapy that
may be an attractive option for the treatment of GAVE. The aim of this study was
to assess the efficacy and safety of RFA for the treatment of GAVE. PATIENTS AND
METHODS: This was an open-label, retrospective, case series study. The main
outcome measures were number of red blood cell (RBC) packs transfused
(transfusion requirement) and hemoglobin concentrations (g/dL) in the 6 months
prior to and after RFA. Success was defined as a decrease in transfusion
requirement in the 6 months after RFA compared with before treatment. RESULTS: A
total of 24 patients underwent a mean of 1.8 +/- 0.8 RFA sessions. No
complications were reported. One patient was referred for additional argon plasma
coagulation during follow-up. The mean number of RBC packs decreased in all 23
transfusion-dependent patients, from a mean of 10.6 +/- 12.1 during the 6 months
prior to RFA, to a mean of 2.5 +/- 5.9 during the 6 months after RFA treatment (P
< 0.001), and 15 patients (65.2 %) were weaned off transfusions completely. An
increase in the hemoglobin concentration was reported in all patients after RFA
(from 6.8 +/- 1.4 g/dL to 9.8 +/- 1.8 g/dL; P < 0.001). CONCLUSION: RFA for the
treatment of GAVE seems feasible and safe, and significantly reduced the need for
RBC transfusion and increased the hemoglobin level in this retrospective case
series.
PMID- 25111136
TI - Deep biopsy via endoscopic submucosal dissection in upper gastrointestinal
subepithelial tumors: a prospective study.
AB - BACKGROUND AND STUDY AIMS: Preoperative pathological diagnosis may improve
clinical management decisions in patients with upper gastrointestinal
subepithelial tumors (SETs). The aims of this study were to evaluate the
diagnostic yield of deep biopsy via an endoscopic submucosal dissection (ESD)
technique, the complications associated with the procedure, and the impact on
management of patients with upper gastrointestinal SETs. PATIENTS AND METHODS: A
total of 68 patients with SETs in the stomach or esophagus were voluntarily
assigned to two groups. One group underwent endoscopic ultrasound (EUS) and
endoscopic deep biopsy using the ESD technique (40 patients), and the other group
(28 patients) underwent surgical resection after EUS without obtaining
preoperative pathological diagnosis, in accordance with accepted clinical
management algorithms. RESULTS: The diagnostic yield of deep biopsy was 90 %
(36/40). The results of deep biopsy changed the treatment plans in 14/40 patients
(35 %). One patient with lymphoepithelial carcinoma was scheduled for surgical
resection, and 13 patients with benign SETs of diameter >= 2 cm avoided surgery.
Of the 28 patients who underwent surgical resection without preoperative
pathological diagnosis, 12 (42.9 %) were confirmed to have benign lesions. The
mean procedure time for deep biopsy was 13.7 minutes. There were no procedure
related complications in the deep biopsy group. CONCLUSIONS: Deep biopsy by the
ESD technique is a safe, high-yield, diagnostic method in patients with upper
gastrointestinal SETs. Pathologic confirmation could improve clinical decision
making in the management of patients with upper gastrointestinal SETs. CLINICAL
TRIAL REGISTRATION: NCT 01993199.
PMID- 25111138
TI - Novel intramedullary-fixation technique for long bone fragility fractures using
bioresorbable materials.
AB - Almost all of the currently available fracture fixation devices for metaphyseal
fragility fractures are made of hard metals, which carry a high risk of implant
related complications such as implant cutout in severely osteoporotic patients.
We developed a novel fracture fixation technique (intramedullary-fixation with
biodegradable materials; IM-BM) for severely weakened long bones using three
different non-metallic biomaterials, a poly(l-lactide) (PLLA) woven tube, a
nonwoven polyhydroxyalkanoates (PHA) fiber mat, and an injectable calcium
phosphate cement (CPC). The purpose of this work was to evaluate the feasibility
of IM-BM with mechanical testing as well as with an animal experiment. To perform
mechanical testing, we fixed two longitudinal acrylic pipes with four different
methods, and used them for a three-point bending test (N = 5). The three-point
bending test revealed that the average fracture energy for the IM-BM group (PLLA
+ CPC + PHA) was 3 times greater than that of PLLA + CPC group, and 60 to 200
times greater than that of CPC + PHA group and CPC group. Using an osteoporotic
rabbit distal femur incomplete fracture model, sixteen rabbits were randomly
allocated into four experimental groups (IM-BM group, PLLA + CPC group, CPC
group, Kirschner wire (K-wire) group). No rabbit in the IM-BM group suffered
fracture displacement even under full weight bearing. In contrast, two rabbits in
the PLLA + CPC group, three rabbits in the CPC group, and three rabbits in the K
wire group suffered fracture displacement within the first postoperative week.
The present work demonstrated that IM-BM was strong enough to reinforce and
stabilize incomplete fractures with both mechanical testing and an animal
experiment even in the distal thigh, where bone is exposed to the highest bending
and torsional stresses in the body. IM-BM can be one treatment option for those
with severe osteoporosis.
PMID- 25111137
TI - Extinction risks and the conservation of Madagascar's reptiles.
AB - BACKGROUND: An understanding of the conservation status of Madagascar's endemic
reptile species is needed to underpin conservation planning and priority setting
in this global biodiversity hotspot, and to complement existing information on
the island's mammals, birds and amphibians. We report here on the first
systematic assessment of the extinction risk of endemic and native non-marine
Malagasy snakes, lizards, turtles and tortoises. METHODOLOGY/PRINCIPAL FINDINGS:
Species range maps from The IUCN Red List of Threatened Species were analysed to
determine patterns in the distribution of threatened reptile species. These data,
in addition to information on threats, were used to identify priority areas and
actions for conservation. Thirty-nine percent of the data-sufficient Malagasy
reptiles in our analyses are threatened with extinction. Areas in the north, west
and south-east were identified as having more threatened species than expected
and are therefore conservation priorities. Habitat degradation caused by wood
harvesting and non-timber crops was the most pervasive threat. The direct removal
of reptiles for international trade and human consumption threatened relatively
few species, but were the primary threats for tortoises. Nine threatened reptile
species are endemic to recently created protected areas.
CONCLUSIONS/SIGNIFICANCE: With a few alarming exceptions, the threatened endemic
reptiles of Madagascar occur within the national network of protected areas,
including some taxa that are only found in new protected areas. Threats to these
species, however, operate inside and outside protected area boundaries. This
analysis has identified priority sites for reptile conservation and completes the
conservation assessment of terrestrial vertebrates in Madagascar which will
facilitate conservation planning, monitoring and wise-decision making. In sharp
contrast with the amphibians, there is significant reptile diversity and regional
endemism in the southern and western regions of Madagascar and this study
highlights the importance of these arid regions to conserving the island's
biodiversity.
PMID- 25111139
TI - The strong selective sweep candidate gene ADRA2C does not explain domestication
related changes in the stress response of chickens.
AB - Analysis of selective sweeps to pinpoint causative genomic regions involved in
chicken domestication has revealed a strong selective sweep on chromosome 4 in
layer chickens. The autoregulatory alpha-adrenergic receptor 2C (ADRA2C) gene is
the closest to the selective sweep and was proposed as an important gene in the
domestication of layer chickens. The ADRA2C promoter region was also
hypermethylated in comparison to the non-selected ancestor of all domesticated
chicken breeds, the Red Junglefowl, further supporting its relevance. In mice the
receptor is involved in the fight-or-flight response as it modulates epinephrine
release from the adrenals. To investigate the involvement of ADRA2C in chicken
domestication, we measured gene expression in the adrenals and radiolabeled
receptor ligand in three brain regions comparing the domestic White Leghorn
strain with the wild ancestor Red Junglefowl. In adrenals ADRA2C was twofold
greater expressed than the related receptor gene ADRA2A, indicating that ADRA2C
is the predominant modulator of epinephrine release but no strain differences
were measured. In hypothalamus and amygdala, regions associated with the stress
response, and in striatum, receptor binding pIC50 values ranged between 8.1-8.4,
and the level was not influenced by the genotyped allele. Because chicken strains
differ in morphology, physiology and behavior, differences attributed to a single
gene may be lost in the noise caused by the heterogeneous genetic background.
Therefore an F10 advanced intercross strain between White Leghorn and Red
Junglefowl was used to investigate effects of ADRA2C alleles on fear related
behaviors and fecundity. We did not find compelling genotype effects in open
field, tonic immobility, aerial predator, associative learning or fecundity.
Therefore we conclude that ADRA2C is probably not involved in the domestication
of the stress response in chicken, and the strong selective sweep is probably
caused by selection of some unknown genetic element in the vicinity of the gene.
PMID- 25111140
TI - Can gas replace protein function? CO abrogates the oxidative toxicity of
myoglobin.
AB - Outside their cellular environments, hemoglobin (Hb) and myoglobin (Mb) are known
to wreak oxidative damage. Using haptoglobin (Hp) and hemopexin (Hx) the body
defends itself against cell-free Hb, yet mechanisms of protection against
oxidative harm from Mb are unclear. Mb may be implicated in oxidative damage both
within the myocyte and in circulation following rhabdomyolysis. Data from the
literature correlate rhabdomyolysis with the induction of Heme Oxygenase-1 (HO
1), suggesting that either the enzyme or its reaction products are involved in
oxidative protection. We hypothesized that carbon monoxide (CO), a product, might
attenuate Mb damage, especially since CO is a specific ligand for heme iron. Low
density lipoprotein (LDL) was chosen as a substrate in circulation and myosin
(My) as a myocyte component. Using oxidation targets, LDL and My, the study
compared the antioxidant potential of CO in Mb-mediated oxidation with the
antioxidant potential of Hp in Hb-mediated oxidation. The main cause of LDL
oxidation by Hb was found to be hemin which readily transfers from Hb to LDL. Hp
prevented heme transfer by sequestering hemin within the Hp-Hb complex. Hemin
barely transferred from Mb to LDL, and oxidation appeared to stem from heme iron
redox in the intact Mb. My underwent oxidative crosslinking by Mb both in air and
under N2. These reactions were fully arrested by CO. The data are interpreted to
suit several circumstances, some physiological, such as high muscle activity, and
some pathological, such as rhabdomyolysis, ischemia/reperfusion and skeletal
muscle disuse atrophy. It appear that CO from HO-1 attenuates damage by
temporarily binding to deoxy-Mb, until free oxygen exchanges with CO to restore
the equilibrium.
PMID- 25111141
TI - Tick surveillance for relapsing fever spirochete Borrelia miyamotoi in Hokkaido,
Japan.
AB - During 2012-2013, a total of 4325 host-seeking adult ticks belonging to the genus
Ixodes were collected from various localities of Hokkaido, the northernmost
island of Japan. Tick lysates were subjected to real-time PCR assay to detect
borrelial infection. The assay was designed for specific detection of the
Relapsing fever spirochete Borrelia miyamotoi and for unspecific detection of
Lyme disease-related spirochetes. Overall prevalence of B. miyamotoi was 2%
(71/3532) in Ixodes persulcatus, 4.3% (5/117) in Ixodes pavlovskyi and 0.1%
(1/676) in Ixodes ovatus. The prevalence in I. persulcatus and I. pavlovskyi
ticks were significantly higher than in I. ovatus. Co-infections with Lyme
disease-related spirochetes were found in all of the tick species. During this
investigation, we obtained 6 isolates of B. miyamotoi from I. persulcatus and I.
pavlovskyi by culture in BSK-M medium. Phylogenetic trees of B. miyamotoi
inferred from each of 3 housekeeping genes (glpQ, 16S rDNA, and flaB)
demonstrated that the Hokkaido isolates were clustered with Russian B. miyamotoi,
but were distinguishable from North American and European B. miyamotoi. A
multilocus sequence analysis using 8 genes (clpA, clpX, nifS, pepX, pyrG, recG,
rplB, and uvrA) suggested that all Japanese B. miyamotoi isolates, including past
isolates, were genetically clonal, although these were isolated from different
tick and vertebrate sources. From these results, B. miyamotoi-infected ticks are
widely distributed throughout Hokkaido. Female I. persulcatus are responsible for
most human tick-bites, thereby I. persulcatus is likely the most important vector
of indigenous relapsing fever from tick bites in Hokkaido.
PMID- 25111142
TI - Children with chronic suppurative lung disease have a reduced capacity to
synthesize interferon-gamma in vitro in response to non-typeable Haemophilus
influenzae.
AB - Chronic suppurative lung disease (CSLD) is characterized by the presence of a
chronic wet or productive cough and recurrent lower respiratory infections. The
aim of this study was to identify features of innate, cell-mediated and humoral
immunity that may increase susceptibility to respiratory infections in children
with CSLD. Because non-typeable Haemophilus influenzae (NTHi) is commonly
isolated from the airways in CSLD, we examined immune responses to this organism
in 80 age-stratified children with CSLD and compared their responses with 51
healthy control children. Cytokines involved in the generation and control of
inflammation (IFN-gamma, IL-13, IL-5, IL-10 at 72 hours and TNFalpha, IL-6, IL-10
at 24 hours) were measured in peripheral blood mononuclear cells challenged in
vitro with live NTHi. We also measured circulating IgG subclass antibodies (IgG1
and IgG4) to two H. influenzae outer membrane proteins, P4 and P6. The most
notable finding was that PBMC from children with CSLD produced significantly less
IFN-gamma in response to NTHi than healthy control children whereas mitogen
induced IFN-gamma production was similar in both groups. Overall there were minor
differences in innate and humoral immune responses between CSLD and control
children. This study demonstrates that children with chronic suppurative lung
disease have an altered systemic cell-mediated immune response to NTHi in vitro.
This deficient IFN-gamma response may contribute to increased susceptibility to
NTHi infections and the pathogenesis of CSLD in children.
PMID- 25111144
TI - Single-channel prototype terahertz endoscopic system.
AB - We demonstrate the design and development of an innovative single-channel
terahertz (THz) prototype endoscopic imaging system based on flexible metal
coated THz waveguides and a polarization specific detection technique. The
continuous-wave (CW) THz imaging system utilizes a single channel to transmit and
collect the reflected intrinsic THz signal from the sample. Since the prototype
system relies on a flexible waveguide assembly that is small enough in diameter,
it can be readily integrated with a conventional optical endoscope. This study
aims to show the feasibility of waveguide enabled THz imaging. We image various
objects in transmission and reflection modes. We also image normal and cancerous
colonic tissues in reflectance mode using a polarization specific imaging
technique. The resulting cross-polarized THz reflectance images showed contrast
between normal and cancerous colonic tissues at 584 GHz. The level of contrast
observed using endoscopic imaging correlates well with contrast levels observed
in ex vivo THz reflectance studies of colon cancer. This indicates that the
single-channel flexible waveguide-based THz endoscope presented here represents a
significant step forward in clinical endoscopic application of THz technology to
aid in in vivo cancer screening.
PMID- 25111143
TI - Characterization of newly isolated lytic bacteriophages active against
Acinetobacter baumannii.
AB - Based on genotyping and host range, two newly isolated lytic bacteriophages,
myovirus vB_AbaM_Acibel004 and podovirus vB_AbaP_Acibel007, active against
Acinetobacter baumannii clinical strains, were selected from a new phage library
for further characterization. The complete genomes of the two phages were
analyzed. Both phages are characterized by broad host range and essential
features of potential therapeutic phages, such as short latent period (27 and 21
min, respectively), high burst size (125 and 145, respectively), stability of
activity in liquid culture and low frequency of occurrence of phage-resistant
mutant bacterial cells. Genomic analysis showed that while Acibel004 represents a
novel bacteriophage with resemblance to some unclassified Pseudomonas aeruginosa
phages, Acibel007 belongs to the well-characterized genus of the Phikmvlikevirus.
The newly isolated phages can serve as potential candidates for phage cocktails
to control A. baumannii infections.
PMID- 25111145
TI - Micrometric precision of prosthetic dental crowns obtained by optical scanning
and computer-aided designing/computer-aided manufacturing system.
AB - The current study evaluated prosthetic dental crowns obtained by optical scanning
and a computer-aided designing/computer-aided manufacturing system using micro
computed tomography to compare the marginal fit. The virtual models were obtained
with four different scanning surfaces: typodont (T), regular impressions (RI),
master casts (MC), and powdered master casts (PMC). Five virtual models were
obtained for each group. For each model, a crown was designed on the software and
milled from feldspathic ceramic blocks. Micro-CT images were obtained for
marginal gap measurements and the data were statistically analyzed by one-way
analysis of variance followed by Tukey's test. The mean vertical misfit was T =
62.6 +/- 65.2 MUm ; MC = 60.4 +/- 38.4 MUm; PMC = 58.1 +/- 38.0 MUm, and RI =
89.8 +/- 62.8 MUm. Considering a percentage of vertical marginal gap of up to 75
MUm, the results were T = 71.5%, RI = 49.2%, MC = 69.6%, and PMC = 71.2%. The
percentages of horizontal overextension were T = 8.5%, RI = 0%, MC = 0.8%, and
PMC = 3.8%. Based on the results, virtual model acquisition by scanning the
typodont (simulated mouth) or MC, with or without powder, showed acceptable
values for the marginal gap. The higher result of marginal gap of the RI group
suggests that it is preferable to scan this directly from the mouth or from MC.
PMID- 25111146
TI - Thermoreversible gel lubricants through universal supramolecular assembly of a
nonionic surfactant in a variety of base lubricating liquids.
AB - The present paper investigates a new type of thermoreversible gel lubricant
obtained by supramolecular assembly of low-molecular-weight organic gelator
(LMWG) in different base oils. The LMWG is a nonionic surfactant with polar
headgroup and hydrophobic tail that can self-assemble through collective
noncovalent intermolecular interactions (H-bonding, hydrophobic interaction) to
form fibrous structures and trap base oils (mineral oils, synthetic oils, and
water) in the as-formed cavities. The gel lubricants are fully thermoreversible
upon heating-up and cooling down and exhibit thixotropic characteristics. This
makes them semisolid lubricants, but they behave like oils. The tribological test
results disclosed that the LMWG could also effectively reduce friction and wear
of sliding pairs compared with base oils without gelator. It is expected that
when being used in oil-lubricated components, such as gear, rolling bearing, and
so on, gel lubricant may effectively avoid base oil leak and evaporation loss and
so is a benefit to operation and lubrication failure for a long time.
PMID- 25111149
TI - Knowledge-based libraries for predicting the geometric preferences of druglike
molecules.
AB - We describe the automated generation of libraries for predicting the geometric
preferences of druglike molecules. The libraries contain distributions of
molecular dimensions based on crystal structures in the Cambridge Structural
Database (CSD). Searching of the libraries is performed in cascade fashion to
identify the most relevant distributions in cases where precise structural
features are poorly represented by existing crystal structures. The libraries are
fully comprehensive for bond lengths, valence angles, and rotamers and produce
templates for the large majority of unfused and fused rings. Geometry
distributions for rotamers and rings take into account any atom chirality that
may be present. Library validation has been performed on a set of druglike
molecules whose structures were published after the latest CSD entry contributing
to the libraries. Hence, the validation gives a true indication of prediction
accuracy.
PMID- 25111147
TI - Treatment efficacy for non-cardiovascular chest pain: a systematic review and
meta-analysis.
AB - BACKGROUND: Non-cardiovascular chest pain (NCCP) leads to impaired quality of
life and is associated with a high disease burden. Upon ruling out cardiovascular
disease, only vague recommendations exist for further treatment. OBJECTIVES: To
summarize treatment efficacy for patients presenting with NCCP. METHODS:
Systematic review and meta-analysis. In July 2013, Medline, Web of Knowledge,
Embase, EBSCOhost, Cochrane Reviews and Trials, and Scopus were searched. Hand
and bibliography searches were also conducted. Randomized controlled trials
(RCTs) evaluating non-surgical treatments in patients with NCCP were included.
Exclusion criteria were poor study quality and small sample size (<10 patients
per group). RESULTS: Thirty eligible RCT's were included. Most studies assessed
PPI efficacy for gastroesophageal reflux disorders (GERD, n = 10). Two RCTs
included musculoskeletal chest pain, seven psychotropic drugs, and eleven various
psychological interventions. Study quality was high in five RCTs and acceptable
in 25. PPI treatment in patients with GERD (5 RCTs, 192 patients) was more
effective than placebo [pooled OR 11.7 (95% CI 5.5 to 25.0, heterogeneity I2 =
6.1%)]. The pooled OR in GERD negative patients (4 RCTs, 156 patients) was 0.8
(95% CI 0.2 to 2.8, heterogeneity I2 = 50.4%). In musculoskeletal NCCP (2 RCTs,
229 patients) manual therapy was more effective than usual care but not than home
exercise [pooled mean difference 0.5 (95% CI -0.3 to 1.3, heterogeneity I2 =
46.2%)]. The findings for cognitive behavioral treatment, serotonin reuptake
inhibitors, tricyclic antidepressants were mixed. Most evidence was available for
cognitive behavioral treatment interventions. LIMITATIONS: Only a small number of
studies were available. CONCLUSIONS: Timely diagnostic evaluation and treatment
of the disease underlying NCCP is important. For patients with suspected GERD,
high-dose treatment with PPI is effective. Only limited evidence was available
for most prevalent diseases manifesting with chest pain. In patients with
idiopathic NCCP, treatments based on cognitive behavioral principles might be
considered.
PMID- 25111151
TI - Axolotls with an under- or oversupply of neural crest can regulate the sizes of
their dorsal root ganglia to normal levels.
AB - How animals adjust the size of their organs is a fundamental, enduring question
in biology. Here we manipulate the amount of neural crest (NC) precursors for the
dorsal root ganglia (DRG) in axolotl. We produce embryos with an under- or over
supply of pre-migratory NC in order to find out if DRG can regulate their sizes
during development. Axolotl embryos are perfectly suitable for this research.
Firstly, they are optimal for microsurgical manipulations and tissue repair.
Secondly, they possess, unlike most other vertebrates, only one neural crest
string located on top of the neural tube. This condition and position enables NC
cells to migrate to either side of the embryo and participate in the regulation
of NC cell distribution. We show that size compensation of DRG in axolotl occurs
in 2 cm juveniles after undersupply of NC (up-regulation) and in 5 cm juveniles
after oversupply of NC (down-regulation). The size of DRG is likely to be
regulated locally within the DRG and not via adaptations of the pre-migratory NC
or during NC cell migration. Ipsi- and contralateral NC cell migration occurs
both in embryos with one and two neural folds, and contralateral migration of NC
is the only source for contralateral DRG formation in embryos with only one
neural fold. Compensatory size increase is accompanied by an increase in cell
division of a DRG precursor pool (PCNA+/SOX2-), rather than by DRG neurons or
glial cells. During compensatory size decrease, increased apoptosis and reduced
proliferation of DRG cells are observed.
PMID- 25111152
TI - Chemical preparation of ferroelectric mesoporous barium titanate thin films:
drastic enhancement of Curie temperature induced by mesopore-derived strain.
AB - Mesoporous barium titanate (BT) thin films are synthesized by a surfactant
assisted sol-gel method. The obtained mesoporous BT thin films show enhanced
ferroelectricity due to the effective strains induced by mesopores. The Curie
temperature (T(c)) of the mesoporous BT reaches approximately 470 degrees C.
PMID- 25111153
TI - High interfacial activity of polymers "grafted through" functionalized iron oxide
nanoparticle clusters.
AB - The mechanism by which polymers, when grafted to inorganic nanoparticles, lower
the interfacial tension at the oil-water interface is not well understood,
despite the great interest in particle stabilized emulsions and foams. A simple
and highly versatile free radical "grafting through" technique was used to bond
high organic fractions (by weight) of poly(oligo(ethylene oxide) monomethyl ether
methacrylate) onto iron oxide clusters, without the need for catalysts. In the
resulting ~1 MUm hybrid particles, the inorganic cores and grafting architecture
contribute to the high local concentration of grafted polymer chains to the
dodecane/water interface to produce low interfacial tensions of only 0.003 w/v %
(polymer and particle core). This "critical particle concentration" (CPC) for
these hybrid inorganic/polymer amphiphilic particles to lower the interfacial
tension by 36 mN/m was over 30-fold lower than the critical micelle concentration
of the free polymer (without inorganic cores) to produce nearly the same
interfacial tension. The low CPC is favored by the high adsorption energy (~10(6)
kBT) for the large ~1 MUm hybrid particles, the high local polymer concentration
on the particles surfaces, and the ability of the deformable hybrid nanocluster
cores as well as the polymer chains to conform to the interface. The nanocluster
cores also increased the entanglement of the polymer chains in bulk DI water or
synthetic seawater, producing a viscosity up to 35,000 cP at 0.01 s(-1), in
contrast with only 600 cP for the free polymer. As a consequence of these
interfacial and rheological properties, the hybrid particles stabilized oil-in
water emulsions at concentrations as low as 0.01 w/v %, with average drop sizes
down to 30 MUm. In contrast, the bulk viscosity was low for the free polymer, and
it did not stabilize the emulsions. The ability to influence the interfacial
activity and rheology of polymers upon grafting them to inorganic particles,
including clusters, may be expected to be broadly applicable to stabilization of
emulsions and foams.
PMID- 25111154
TI - Interplay between cellular activity and three-dimensional scaffold-cell
constructs with different foam structure processed by electron beam melting.
AB - The cellular activity, biological response, and consequent integration of
scaffold-cell construct in the physiological system are governed by the ability
of cells to adhere, proliferate, and biomineralize. In this regard, we combine
cellular biology and materials science and engineering to fundamentally elucidate
the interplay between cellular activity and interconnected three-dimensional
foamed architecture obtained by a novel process of electron beam melting and
computational tools. Furthermore, the organization of key proteins, notably,
actin, vinclulin, and fibronectin, involved in cellular activity and biological
functions and relationship with the structure was explored. The interconnected
foamed structure with ligaments was favorable to cellular activity that includes
cell attachment, proliferation, and differentiation. The primary rationale for
favorable modulation of cellular functions is that the foamed structure provided
a channel for migration and communication between cells leading to highly
mineralized extracellular matrix (ECM) by the differentiating osteoblasts. The
filopodial interaction amongst cells on the ligaments was a governing factor in
the secretion of ECM, with consequent influence on maturation and mineralization.
PMID- 25111156
TI - The introduction of dengue vaccine may temporarily cause large spikes in
prevalence.
AB - A dengue vaccine is expected to be available within a few years. Once vaccine is
available, policy-makers will need to develop suitable policies to allocate the
vaccine. Mathematical models of dengue transmission predict complex temporal
patterns in prevalence, driven by seasonal oscillations in mosquito abundance. In
particular, vaccine introduction may induce a transient period immediately after
vaccine introduction where prevalence can spike higher than in the pre
vaccination period. These spikes in prevalence could lead to doubts about the
vaccination programme among the public and even among decision-makers, possibly
impeding the vaccination programme. Using simple dengue transmission models, we
found that large transient spikes in prevalence are robust phenomena that occur
when vaccine coverage and vaccine efficacy are not either both very high or both
very low. Despite the presence of transient spikes in prevalence, the models
predict that vaccination does always reduce the total number of infections in the
15 years after vaccine introduction. We conclude that policy-makers should
prepare for spikes in prevalence after vaccine introduction to mitigate the
burden of these spikes and to accurately measure the effectiveness of the vaccine
programme.
PMID- 25111157
TI - Enzyme immobilised novel core-shell superparamagnetic nanocomposites for
enantioselective formation of 4-(R)-hydroxycyclopent-2-en-1-(S)-acetate.
AB - Lipase immobilized novel high surface area core-shell superparamagnetic
nanoparticles have been fabricated and used as efficient reusable catalysts for
the selective production of pharmaceutically important chiral isomers from meso
cyclopent-2-en-1,4-diacetate.
PMID- 25111155
TI - An integrative omics strategy to assess the germ cell secretome and to decipher
sertoli-germ cell crosstalk in the Mammalian testis.
AB - Mammalian spermatogenesis, which takes place in complex testicular structures
called seminiferous tubules, is a highly specialized process controlled by the
integration of juxtacrine, paracrine and endocrine information. Within the
seminiferous tubules, the germ cells and Sertoli cells are surrounded by
testicular fluid (TF), which probably contains most of the secreted proteins
involved in crosstalk between these cells. It has already been established that
germ cells can modulate somatic Sertoli cell function through the secretion of
diffusible factors. We studied the germ cell secretome, which was previously
considered inaccessible, by analyzing the TF collected by microsurgery in an
"integrative omics" strategy combining proteomics, transcriptomics, genomics and
interactomics data. This approach identified a set of proteins preferentially
secreted by Sertoli cells or germ cells. An interaction network analysis revealed
complex, interlaced cell-cell dialog between the secretome and membranome of
seminiferous cells, mediated via the TF. We then focused on germ cell-secreted
candidate proteins, and we identified several potential interacting partners
located on the surface of Sertoli cells. Two interactions, APOH/CDC42 and
APP/NGFR, were validated in situ, in a proximity ligation assay (PLA). Our
results provide new insight into the crosstalk between germ cells and Sertoli
cells occurring during spermatogenesis. Our findings also demonstrate that this
"integrative omics" strategy is powerful enough for data mining and highlighting
meaningful cell-cell communication events between different types of cells in a
complex tissue, via a biological fluid. This integrative strategy could be
applied more widely, to gain access to secretomes that have proved difficult to
study whilst avoiding the limitations of in vitro culture.
PMID- 25111158
TI - Single-victim and serial sexual homicide offenders: differences in crime,
paraphilias and personality traits.
AB - BACKGROUND: Information on psychopathological characteristics of sexual homicide
offenders is scarce. AIMS: To investigate criminal, paraphilic and personality
trait differences between serial and single-victim sexual homicide offenders.
METHODS: All 73 single-victim and 13 serial sexual homicide offenders presenting
within a cohort of 671 men sentenced for sexual crimes between 1994 and 2005 and
serving their sentence in one high-security Canadian prison and who consented to
interview were assessed and compared on their offending patterns, personality
pathology and paraphilic behaviours. RESULTS: Serial sexual homicide offenders
were more likely than the single offenders to report deviant sexual fantasies,
having selected victims with distinctive characteristics, to have targeted
strangers, structured premeditation and/or verbal humiliation of their victims
during the offences. Personality pathology, defined by at least two Diagnostic
and Statistical Manual of Mental Disorders IV criteria for personality disorder,
was common in both groups, but the serial offenders were more likely to have
narcissistic, schizoid and/or obsessive-compulsive traits; they were also more
likely to engage in sexual masochism, partialism, homosexual paedophilia,
exhibitionism and/or voyeurism. IMPLICATIONS FOR PRACTICE: Samples of serial
sexual homicide offenders will, fortunately, always be small, and it may be that
more could be learned to assist in preventing such crimes if data from several
studies or centres were pooled. Our findings suggest that an investigation of
sexual homicide offenders should include strategies for evaluating premeditation
as well as personality and paraphilic characteristics. Crime scene features that
should alert investigators should include similar characteristics between victims
and particular aspects of body exposure or organisation.
PMID- 25111159
TI - Dynamic relationships between motor skill competence and health-related fitness
in youth.
AB - This cross-sectional study examined associations among motor skill competence
(MSC) and health-related fitness (HRF) in youth. A convenient sample of 253 boys
and 203 girls (aged 4-13 years) participated in the study. Associations among
measures of MSC (throwing and kicking speed and standing long jump distance) and
a composite measure of HRF (push-ups, curl-ups, grip strength and PACER test)
across five age groups (4-5, 6-7, 8-9, 10-11 and 12-13 yrs.) were assessed using
hierarchical regression modeling. When including all children, throwing and
jumping were significantly associated with the composite HRF factor for both boys
and girls (throw, t = 5.33; jump, t = 4.49) beyond the significant age effect (t
= 4.98) with kicking approaching significance (t = 1.73, p = .08). Associations
between throwing and kicking speed and HRF appeared to increase from early to
middle to late childhood age ranges. Associations between jumping and HRF were
variable across age groups. These results support the notion that the
relationship between MSC and HRF performance are dynamic and may change across
childhood. These data suggest that the development of object control skills in
childhood may be important for the development and maintenance of HRF across
childhood and into adolescence.
PMID- 25111160
TI - Modified Chrispin-Norman score: correlation with peak exercise capacity and
efficiency of ventilation in children with cystic fibrosis.
AB - The modified Chrispin-Norman radiography score (CNS) is used in evaluation of
radiographic changes in children with cystic fibrosis (CF). We evaluated the
correlation of modified CNS with peak exercise capacity (Wpeak) and ventilatory
efficiency (reflected by breathing reserve index-BRI) during progressive
cardiopulmonary exercise testing (CPET). Thirty-six children aged 8-17 years were
stratified according to their CNS into 3 groups: mild (<10), moderate (10-15),
and severe (>15). CPET was performed on a cycle ergometer. Lung function tests
included spirometry and whole-body plethysmography. Patients with higher CNS had
lower FEV1 (p < .001), Wpeak predicted (%; p = .01) and lower mean peak oxygen
consumption (VO2peak/kg; p = .014). The BRI at the anaerobic threshold and at
Wpeak was elevated in patients with the highest CNS values (p < .001). The
modified CNS correlates moderately with Wpeak (R = -0.443; p = .007) and BRI (R =
-0.419; p = .011). Stepwise multiple linear regression showed that RV/TLC was the
best predictor of Wpeak/pred (%; B = -0.165; ? = -0.494; R2 = .244; p = .002).
Children with CF who have high modified CNS exhibit decreased exercise tolerance
and ventilatory inefficacy during progressive effort.
PMID- 25111161
TI - Running activity profile of adolescent tennis players during match play.
AB - The aims of this study were (1) to assess the running activities of adolescent
tennis players during match play with respect to velocity, acceleration, and
deceleration; (2) to characterize changes in these activities during the course
of a match; and (3) to identify potential differences between winners and losers.
Twenty well-trained adolescent male athletes (13 +/- 1 y) played one simulated
match each (giving a total of 10 matches), during which distances covered at
different velocity categories (0 to < 1, 1 to < 2, 2 to < 3, 3 to < 4, and >= 4
m.s(-1)) and number of running activities involving high velocity (>= 3 m.s(-1)),
acceleration (>= 2 m.s(-2)), and deceleration (<= -2 m.s(-2)) were monitored
using a global positioning system (10 Hz). Heart rate was also assessed. The
total match time, total distance covered, peak velocity, and mean heart rate were
81.2 +/- 14.6 min, 3362 +/- 869 m, 4.4 +/- 0.8 m.s(-1), and 159 +/- 12 beats.min(
1), respectively. Running activities involving high acceleration (0.6 +/- 0.2
n.min(-1)) or deceleration (0.6 +/- 0.2 n.min(-1)) were three times as frequent
as those involving high velocity (0.2 +/- 0.1 n.min(-1)). No change in the
pattern of running activities (P >= .13, d <= 0.39) and no differences between
winners and losers (P >= .22, d <= 0.53) were evident during match play. We
conclude that training of well-trained adolescent male tennis players need not
focus on further development of their running abilities, since this physical
component of multifactorial tennis performance does not change during the course
of a match and does not differ between the winners and losers.
PMID- 25111162
TI - From filter paper to porous carbon composite membrane oxygen reduction catalyst.
AB - A novel type of porous carbon composite membrane (PCCM) based on the low-cost
common filter paper via a simple route is reported. The obtained material
exhibited excellent electrocatalytic activities toward the oxygen reduction
reaction, high tolerance of methanol crossover, and durability in alkaline
solution.
PMID- 25111163
TI - Muscle activity and spine load during anterior chain whole body linkage
exercises: the body saw, hanging leg raise and walkout from a push-up.
AB - This study examined anterior chain whole body linkage exercises, namely the body
saw, hanging leg raise and walkout from a push-up. Investigation of these
exercises focused on which particular muscles were challenged and the magnitude
of the resulting spine load. Fourteen males performed the exercises while muscle
activity, external force and 3D body segment motion were recorded. A
sophisticated and anatomically detailed 3D model used muscle activity and body
segment kinematics to estimate muscle force, and thus sensitivity to each
individual's choice of motor control for each task. Gradations of muscle activity
and spine load characteristics were observed across tasks. On average, the
hanging straight leg raise created approximately 3000 N of spine compression
while the body saw created less than 2500 N. The hanging straight leg raise
created the highest challenge to the abdominal wall (>130% MVC in rectus
abdominis, 88% MVC in external oblique). The body saw resulted in almost 140% MVC
activation of the serratus anterior. All other exercises produced substantial
abdominal challenge, although the body saw did so in the most spine conserving
way. These findings, along with consideration of an individual's injury history,
training goals and current fitness level, should assist in exercise choice and
programme design.
PMID- 25111164
TI - Coxsackievirus can persist in murine pancreas by deletion of 5' terminal genomic
sequences.
AB - Enterovirus infections are generally acute and rapidly cleared by the host immune
response. Enteroviruses can at times persist in immunologically intact
individuals after the rise of the type-specific neutralizing immune response. The
mechanism of enterovirus persistence was shown in group B coxsackieviruses (CVB)
to be due to naturally-occurring deletions at the 5' terminus of the genome which
variably impact the stem-loop secondary structure called domain I. These
deletions result in much slower viral replication and a loss of measurable
cytopathic effect when such 5' terminally deleted (TD) viruses are assayed in
cell culture. The existence and persistence of CVB-TD long after the acute phase
of infection has been documented in hearts of experimentally inoculated mice and
naturally infected humans but to date, the existence of TD enteroviral
populations have not been documented in any other organ. Enteroviral infections
have been shown to impact type 1 diabetes (T1D) onset in humans as well as in the
non-obese diabetic mouse model of T1D. The first step to studying the potential
impact of CVB-TD on T1D etiology is to determine whether CVB-TD populations can
arise in the pancreas. After inoculation of NOD diabetic mice with CVB, viral RNA
persists in the absence of cytopathic virus in pancreas weeks past the acute
infectious period. Analysis of viral genomic 5' termini by RT-PCR showed CVB-TD
populations displace the parental population during persistent replication in
murine pancreata.
PMID- 25111165
TI - Hydrogen peroxide enhances the oxidation of oxygenated volatile organic compounds
on mineral dust particles: a case study of methacrolein.
AB - Heterogeneous oxidation of oxygenated volatile organic compounds (OVOCs) serves
as an important sink of OVOCs as well as a source of secondary organic material.
However, the roles of gas phase oxidants in these reactions are poorly
understood. In this work, we present the first laboratory study of the
heterogeneous reactions of methacrolein (MACR) on various mineral dust particles
in the presence of gaseous H2O2. It is found that the presence of gaseous H2O2
significantly promotes both the uptake and oxidation of MACR on kaolinite, alpha
Al2O3, alpha-Fe2O3, and TiO2, but not on CaCO3. The oxidation of MACR produces
organic acids as its major low-molecular-weight product, whose yields are
enhanced by a factor of 2-6 in the presence of H2O2. In addition, organic
peroxides such as methyl hydroperoxide, peroxyformic acid, and peroxyacetic acid
are only formed in the presence of H2O2, and the formation of methyl
hydroperoxide indicates that MACR oxidation on the surface involves reaction with
OH radicals. A probe reaction using salicylic acid verifies the production of OH
radicals from H2O2 decomposition on kaolinite, alpha-Al2O3, alpha-Fe2O3, and
TiO2, which rationalizes the enhanced MACR oxidation observed on these particles.
The uptake coefficients of MACR on kaolinite, alpha-Fe2O3, and TiO2 in the
presence of H2O2 are on the order of 10(-5)-10(-4). Our results provide new
insights into the formation and chemical evolution of organic species in the
atmosphere.
PMID- 25111167
TI - Impact of an adherence program to antiretroviral treatment on virologic response
in a cohort of multitreated and poorly adherent HIV-infected patients in Spain.
AB - Several studies have shown the importance of adherence to highly active
antiretroviral therapy (HAART) in achieving HIV-1 suppression. However, most have
focused on naive patients and do not assess the impact of HAART on viral load
(VL). Our aim was to evaluate the effectiveness of an adherence program in a
cohort of multitreated and poorly adherent patients. We performed a cohort study
of all adult HIV-1 infected patients with detectable VL who were treatment
experienced and poorly adherent to HAART, included in an adherence program since
its introduction in 2009 (n=136). The adherence program consisted of a
multidisciplinary team with a nurse who specialized in behavioral intervention,
counselling on substance abuse, and motivational interviewing, as well as a
social worker responsible for referring patients to local healthcare centers.
Effectiveness was evaluated as percentage of patients with VL <50 copies/mL at
week 48 by modified intent-to-treat (mITT) analysis. Initially, 76.6% of the
patients had an adherence <30% according to the Simplified Medication Adherence
Questionnaire (SMAQ). At 48 weeks, 48.1% of the patients had VL <50 copies/mL,
and the adherence was >90% in 71% of the patients. In multivariate analysis, a
ratio of bottle refill per month >0.9 during the study [odds ratio (OR) 14.3; 95%
confidence interval (CI) 4.08-50.08, p<0.001] and being on a b.i.d. regimen (OR
12.5; 95% CI 1.81-86.4, p=0.010) were associated with an undetectable VL. In
conclusion, the adherence program was successful in almost half of the patients,
despite their long treatment experience and prior poor adherence. This strategy
may help to prevent disease progression and the risk of HIV transmission in these
patients.
PMID- 25111168
TI - Field effectiveness of hepatitis A vaccine and uptake of post exposure
prophylaxis following a change to the Australian guidelines.
AB - BACKGROUND: In 2009, national guidelines for hepatitis A control in Australia
changed to recommend hepatitis A vaccine (HAV), instead of normal human immune
globulin (NHIG), for post-exposure prophylaxis (PEP). AIMS: (1) Determine whether
the uptake of PEP among contacts of hepatitis A cases changed after the
introduction of the new guidelines, and (2) assess the field effectiveness of the
HAV used as PEP in preventing infection among contacts of hepatitis A cases.
METHODS: A retrospective cohort of contacts from hepatitis A cases reported to
metropolitan Public Health Units in Sydney, Australia, between October 2008 and
June 2010, was identified. Contacts were analysed by time period, age, PEP type,
and susceptibility to hepatitis A. The relative risk (RR) of hepatitis A
infection among susceptible contacts who received HAV, compared with susceptible
contacts who had not received HAV, was calculated to estimate the effectiveness
of the HAV when used as PEP. RESULTS: The uptake of PEP by susceptible contacts
increased from 76% (n=133) to 89% (n=127) after the introduction of the new
guidelines. Before the change in guidelines, no one who received PEP was later
reported with hepatitis A. After the change in guidelines, one of the 123
contacts who received HAV as PEP was subsequently reported with hepatitis A.
However, this case was likely to have been co-exposed with a primary case.
Conservatively, assuming this was a secondary case, the vaccine effectiveness of
HAV was 95.6% (66.1%-99.4%). Nine of 10 incident cases of hepatitis A were
contacts who did not receive any PEP. CONCLUSION: The improved uptake of PEP and
the high estimate of the effectiveness of HAV provides support for using HAV for
PEP. The very high occurrence of hepatitis A among contacts who did not receive
any PEP further highlights the importance of PEP in preventing hepatitis A
infection.
PMID- 25111166
TI - Effects of the absence of apolipoprotein e on lipoproteins, neurocognitive
function, and retinal function.
AB - IMPORTANCE: The identification of a patient with a rare form of severe
dysbetalipoproteinemia allowed the study of the consequences of total absence of
apolipoprotein E (apoE). OBJECTIVES: To discover the molecular basis of this rare
disorder and to determine the effects of complete absence of apoE on
neurocognitive and visual function and on lipoprotein metabolism. DESIGN,
SETTING, AND PARTICIPANTS: Whole-exome sequencing was performed on the patient's
DNA. He underwent detailed neurological and visual function testing and
lipoprotein analysis. Lipoprotein analysis was also performed in the
Cardiovascular Research Institute, University of California, San Francisco, on
blood samples from the proband's mother, wife, 2 daughters, and normolipidemic
control participants. MAIN OUTCOME MEASURES: Whole-exome sequencing, lipoprotein
analysis, and neurocognitive function. RESULTS: The patient was homozygous for an
ablative APOE frameshift mutation (c.291del, p.E97fs). No other mutations likely
to contribute to the phenotype were discovered, with the possible exception of
two, in ABCC2 (p.I670T) and LIPC (p.G137R). Despite complete absence of apoE, he
had normal vision, exhibited normal cognitive, neurological, and retinal
function, had normal findings on brain magnetic resonance imaging, and had normal
cerebrospinal fluid levels of beta-amyloid and tau proteins. He had no
significant symptoms of cardiovascular disease except a suggestion of myocardial
ischemia on treadmill testing and mild atherosclerosis noted on carotid
ultrasonography. He had exceptionally high cholesterol content (760 mg/dL; to
convert to millimoles per liter, multiply by 0.0259) and a high cholesterol to
triglycerides ratio (1.52) in very low-density lipoproteins with elevated levels
of small-diameter high-density lipoproteins, including high levels of prebeta-1
high-density lipoprotein. Intermediate-density lipoproteins, low-density
lipoproteins, and very low-density lipoproteins contained elevated apoA-I and
apoA-IV levels. The patient's apoC-III and apoC-IV levels were decreased in very
low-density lipoproteins. Electron microscopy revealed large lamellar particles
having electron-opaque cores attached to electron-lucent zones in intermediate
density and low-density lipoproteins. Low-density lipoprotein particle diameters
were distributed bimodally. CONCLUSIONS AND RELEVANCE: Despite a profound effect
on lipoprotein metabolism, detailed neurocognitive and retinal studies failed to
demonstrate any defects. This suggests that functions of apoE in the brain and
eye are not essential or that redundant mechanisms exist whereby its role can be
fulfilled. Targeted knockdown of apoE in the central nervous system might be a
therapeutic modality in neurodegenerative disorders.
PMID- 25111170
TI - Highly drug-resistant pathogens implicated in burn-associated bacteremia in an
Iraqi burn care unit.
AB - OBJECTIVE: In low- and middle-income countries, bloodstream infections are an
important cause of mortality in patients with burns. Increasingly implicated in
burn-associated infections are highly drug-resistant pathogens with limited
treatment options. We describe the epidemiology of bloodstream infections in
patients with burns in a humanitarian surgery project in Iraq. METHODS: We
performed a retrospective, descriptive study of blood culture isolates identified
between July 2008 and September 2009 among patients with burns in a single
hospital in Iraq who developed sepsis. RESULTS: In 1169 inpatients admitted to
the burn unit during the study period, 212 (18%) had suspected sepsis, and 65
(6%) had confirmed bacteremia. Sepsis was considered the primary cause of death
in 198 patients (65%; 95% CI 65-70) of the 304 patients that died. The most
commonly isolated organisms were Pseudomonas aeruginosa (22 isolates [34%]),
Staphylococcus aureus (17 [26%]), Klebsiella pneumoniae (8 [12%]), Staphylococcus
epidermidis (7 [11%]), Acinetobacter baumannii (6 [9%]), and Enterobacter cloacae
(5 [8%]). A high proportion of Enterobacteriaceae strains produced extended
spectrum beta-lactamase and S. aureus isolates were uniformly methicillin
resistant. For gram-negative bacteria, the most reliably active antibiotics were
imipenen and amikacin. CONCLUSIONS: Burn patients with sepsis in Iraq were
commonly found to have bloodstream pathogens resistant to most antibiotics
available locally. Effective empirical therapy of burn sepsis in this region of
Iraq would consist of vancomycin or teicoplanin and a carbapenem-class antibiotic
with antipseudomonal activity.
PMID- 25111172
TI - Long-term outcome in PSC/AIH "overlap syndrome": does immunosuppression also
treat the PSC component?
PMID- 25111169
TI - Adjuvants for vaccines to drugs of abuse and addiction.
AB - Immunotherapeutic vaccines to drugs of abuse, including nicotine, cocaine,
heroin, oxycodone, methamphetamine, and others are being developed. The
theoretical basis of such vaccines is to induce antibodies that sequester the
drug in the blood in the form of antibody-bound drug that cannot cross the blood
brain barrier, thereby preventing psychoactive effects. Because the drugs are
haptens a successful vaccine relies on development of appropriate hapten-protein
carrier conjugates. However, because induction of high and prolonged levels of
antibodies is required for an effective vaccine, and because injection of T
independent haptenic drugs of abuse does not induce memory recall responses, the
role of adjuvants during immunization plays a critical role. As reviewed herein,
preclinical studies often use strong adjuvants such as complete and incomplete
Freund's adjuvant and others that cannot be, or in the case of many newer
adjuvants, have never been, employed in humans. Balanced against this, the only
adjuvant that has been included in candidate vaccines in human clinical trials to
nicotine and cocaine has been aluminum hydroxide gel. While aluminum salts have
been widely utilized worldwide in numerous licensed vaccines, the experience with
human responses to aluminum salt-adjuvanted vaccines to haptenic drugs of abuse
has suggested that the immune responses are too weak to allow development of a
successful vaccine. What is needed is an adjuvant or combination of adjuvants
that are safe, potent, widely available, easily manufactured, and cost-effective.
Based on our review of the field we recommend the following adjuvant combinations
either for research or for product development for human use: aluminum salt with
adsorbed monophosphoryl lipid A (MPLA); liposomes containing MPLA [L(MPLA)];
L(MPLA) adsorbed to aluminum salt; oil-in-water emulsion; or oil-in-water
emulsion containing MPLA.
PMID- 25111171
TI - Changing indications and socio-demographic determinants of (adeno)tonsillectomy
among children in England--are they linked? A retrospective analysis of hospital
data.
AB - OBJECTIVE: To assess whether increased awareness and diagnosis of obstructive
sleep apnoea syndrome (OSAS) and national guidance on tonsillectomy for recurrent
tonsillitis have influenced the socio-demographic profile of children who
underwent tonsillectomy over the last decade. METHOD: Retrospective time-trends
study of Hospital Episodes Statistics data. We examined the age, sex and
deprivation level, alongside OSAS diagnoses, among children aged <16 years who
underwent (adeno)tonsillectomy in England between 2001/2 and 2011/12. RESULTS:
Among children aged <16 years, there were 29,697 and 27,732
(adeno)tonsillectomies performed in 2001/2 and 2011/12, respectively. The median
age at (adeno)tonsillectomy decreased from 7 (IQR: 5-11) to 5 (IQR: 4-9) years
over the decade. (Adeno)tonsillectomy rates among children aged 4-15 years
decreased by 14% from 350 (95%CI: 346-354) in 2001/2 to 300 (95%CI: 296-303) per
100,000 children in 2011/12. However, (adeno)tonsillectomy rates among children
aged <4 years increased by 58% from 135 (95%CI: 131-140) to 213 (95%CI 208-219)
per 100,000 children in 2001/2 and 2011/2, respectively. OSAS diagnoses among
children aged <4 years who underwent surgery increased from 18% to 39% between
these study years and the proportion of children aged <4 years with OSAS from the
most deprived areas increased from 5% to 12%, respectively. CONCLUSIONS:
(Adeno)tonsillectomy rates declined among children aged 4-15 years, which
reflects national guidelines recommending the restriction of the operation to
children with more severe recurrent throat infections. However,
(adeno)tonsillectomy rates among pre-school children substantially increased over
the past decade and one in five children undergoing the operation was aged <4
years in 2011/12.The increase in surgery rates in younger children is likely to
have been driven by increased awareness and detection of OSAS, particularly among
children from the most deprived areas.
PMID- 25111173
TI - Monitoring dominant strictures in primary sclerosing cholangitis with brush
cytology and FDG-PET.
AB - BACKGROUND & AIMS: Despite a high risk of cholangiocellular adenocarcinoma (CCA)
it is unclear how surveillance of patients with primary sclerosing cholangitis
(PSC) should be performed. METHODS: We evaluated a follow-up algorithm of brush
cytology and positron emission tomography/computed tomography with [(18)F]
fluorodeoxyglucose ([(18)F]FDG-PET/CT), measured as maximum standardized uptake
values, normalized to the liver background (SUVmax/liver) at 180 min, in PSC
patients with dominant bile duct strictures. RESULTS: Brush cytology with high
grade dysplasia (HGD) was detected in 12/70 patients (17%), yielding a diagnostic
sensitivity, specificity, positive predictive value (PPV), and negative
predictive value (NPV) of 56%, 89%, 75%, and 88%, respectively. Preemptive liver
transplantations due to repeated HGD before manifest CCA were performed in six
patients. Receiver operating characteristic (ROC) analysis of [(18)F]FDG uptake
showed that a SUVmax/liver quotient of 3.3 was able to discriminate between CCA
and non-malignant disease with a sensitivity, specificity, PPV and NPV for CCA of
89%, 92%, 62%, 98%, respectively. A SUVmax/liver >3.3 detected CCA in 8/9
patients whereas a quotient <2.4 excluded CCA. Combining brush cytology and
quantitative [(18)F]FDG-PET/CT yielded a sensitivity for HGD and/or CCA of 100%
and a specificity of 88%. CONCLUSION: Early detection of HGD before manifest CCA
is feasible with repeated brush cytology and may allow for preemptive liver
transplantation. [(18)F]FDG-PET/CT has a high sensitivity for manifest CCA and a
negative scan indicates a non-malignant state of the disease. Brush cytology and
[(18)F]FDG-PET/CT are complementary in monitoring and managing PSC patients with
dominant strictures.
PMID- 25111175
TI - The effect of brain death in rat steatotic and non-steatotic liver
transplantation with previous ischemic preconditioning.
AB - BACKGROUND & AIMS: Most liver grafts undergoing transplantation derive from brain
dead donors, which may also show hepatic steatosis, being both characteristic
risk factors in liver transplantation. Ischemic preconditioning shows benefits
when applied in non-brain dead clinical situations like hepatectomies, whereas it
has been less promising in the transplantation from brain dead patients. This
study examined how brain death affects preconditioned steatotic and non-steatotic
liver grafts undergoing transplantation. METHODS: Steatotic and non-steatotic
grafts from non-brain dead and brain dead-donors were cold stored for 6h and then
transplanted. After 2, 4, and 16 h of reperfusion, hepatic damage was analysed.
In addition, two therapeutic strategies, ischemic preconditioning and/or
acetylcholine pre-treatment, and their underlying mechanisms were characterized.
RESULTS: Preconditioning benefits in non-brain dead donors were associated with
nitric oxide and acetylcholine generation. In brain dead donors, preconditioning
generated nitric oxide but did not promote acetylcholine upregulation, and this
resulted in inflammation and damage. Acetylcholine treatment in brain dead
donors, through PKC, increased antioxidants and reduced lipid peroxidation,
nitrotyrosines and neutrophil accumulation, altogether protecting against damage.
The combination of acetylcholine and preconditioning conferred stronger
protection against damage, oxidative stress and neutrophil accumulation than
acetylcholine treatment alone. These superior beneficial effects were due to a
selective preconditioning-mediated generation of nitric oxide and regulation of
PPAR and TLR4 pathways, which were not observed when acetylcholine was
administered alone. CONCLUSIONS: Our findings propose the combination of
acetylcholine+preconditioning as a feasible and highly protective strategy to
reduce the adverse effects of brain death and to ultimately improve liver graft
quality.
PMID- 25111174
TI - Correction of hyponatraemia improves cognition, quality of life, and brain oedema
in cirrhosis.
AB - BACKGROUND & AIMS: Hyponatraemia in cirrhosis is associated with impaired
cognition and poor health-related quality of life (HRQOL). However, the benefit
of hyponatraemia correction is unclear. The aim of this study was to evaluate the
effect of tolvaptan on serum sodium (Na), cognition, HRQOL, companion burden, and
brain MRI (volumetrics, spectroscopy, and diffusion tensor imaging) in cirrhotics
with hyponatraemia. METHODS: Cirrhotics with Na <130 mEq/L were included for a
four-week trial. At screening, patients underwent cognitive and HRQOL testing,
serum/urine chemistries and companion burden assessment. Patients then underwent
fluid restriction and diuretic withdrawal for two weeks after which cognitive
tests were repeated. If Na was still <130 mEq/L, brain magnetic resonance imaging
(MRI) was performed and tolvaptan was initiated for 14 days with frequent
clinical/laboratory monitoring. After 14 days of tolvaptan, all tests were
repeated. Comparisons were made between screen, pre-and post-drug periods Na,
urine/serum laboratories, cognition, HRQOL and companion burden. RESULTS: 24
cirrhotics were enrolled; seven normalized Na without tolvaptan with improvement
in cognition. The remaining 17 received tolvaptan of which 14 completed the study
over 13 +/- 2 days (age 58 +/- 6 years, MELD 17, 55% HCV, median 26 mg/day of
tolvaptan). Serum Na and urine free water clearance increased with tolvaptan
without changes in mental status or liver function. Cognitive function, HRQOL and
companion burden only improved in these 14 patients after tolvaptan, along with
reduced total brain and white matter volume, increase in choline on magnetic
resonance spectroscopy, and reduced cytotoxic oedema. CONCLUSIONS: Short-term
tolvaptan therapy is well tolerated in cirrhosis. Hyponatraemia correction is
associated with cognitive, HRQOL, brain MRI and companion burden improvement.
PMID- 25111177
TI - Genetic predisposition to hepatocellular carcinoma in alcoholic cirrhosis: the
NCAN-PNPLA3-lipid connection?
PMID- 25111176
TI - S100A4 promotes liver fibrosis via activation of hepatic stellate cells.
AB - BACKGROUND & AIMS: S100A4 has been linked to the fibrosis of several organs due
to its role as a fibroblast-specific marker. However, the role of S100A4 itself
in the development of fibrosis has not been much investigated. Here, we
determined whether S100A4 regulates liver fibrogenesis and examined its mechanism
by focusing on the activation of hepatic stellate cells (HSCs). METHODS: S100A4
deficient mice were used to determine the role of S100A4 in liver fibrogenesis.
The effect of S100A4 on HSC activation was estimated by using primary mouse HSCs
and the human HSC cell line LX-2. Serum levels of S100A4 in cirrhotic patients
were determined by ELISA. RESULTS: S100A4 was found to be secreted by a
subpopulation of macrophages and to promote the development of liver fibrosis. It
accumulated in the liver during the progression of liver fibrosis and activated
HSCs in mice. In vitro studies demonstrated that S100A4 induced the
overexpression of alpha-smooth muscle actin through c-Myb in HSCs. Both, the
selective depletion of S100A4-expressing cells and knockdown of S100A4 in the
liver by RNA interference, resulted in a reduction of liver fibrosis following
injury. Importantly, increased S100A4 levels in both the liver tissue and serum
correlated positively with liver fibrosis in humans. CONCLUSIONS: S100A4 promotes
liver fibrosis by activating HSCs, which may represent a potential target for
anti-fibrotic therapies.
PMID- 25111178
TI - A high throughput screen identifies potent and selective inhibitors to human
epithelial 15-lipoxygenase-2.
AB - Lipoxygenase (LOX) enzymes catalyze the hydroperoxidation of arachidonic acid and
other polyunsaturated fatty acids to hydroxyeicosatetraenoic acids with varying
positional specificity to yield important biological signaling molecules. Human
epithelial 15-lipoxygenase-2 (15-LOX-2) is a highly specific LOX isozyme that is
expressed in epithelial tissue and whose activity has been correlated with
suppression of tumor growth in prostate and other epithelial derived cancers.
Despite the potential utility of an inhibitor to probe the specific role of 15
LOX-2 in tumor progression, no such potent/specific 15-LOX-2 inhibitors have been
reported to date. This study employs high throughput screening to identify two
novel, specific 15-LOX-2 inhibitors. MLS000545091 is a mixed-type inhibitor of 15
LOX-2 with a Ki of 0.9+/-0.4 uM and has a 20-fold selectivity over 5-LOX, 12-LOX,
15-LOX-1, COX-1, and COX-2. MLS000536924 is a competitive inhibitor with a Ki of
2.5+/-0.5 uM and also possesses 20-fold selectivity toward 15-LOX-2 over the
other oxygenases, listed above. Finally, neither compound possesses reductive
activity towards the active-site ferrous ion.
PMID- 25111179
TI - Characterization of nodal/TGF-lefty signaling pathway gene variants for possible
roles in congenital heart diseases.
AB - BACKGROUND: Nodal/TGF-Lefty signaling pathway has important effects at early
stages of differentiation of human embryonic stem cells in directing them to
differentiate into different embryonic lineages. LEFTY, one of transforming
growth factors in the Nodal/TGF-Lefty signaling pathway, plays an important role
in the development of heart. The aim of this work was to find evidence on whether
Lefty variations are associated with congenital heart diseases (CHD). METHODS: We
sequenced the Lefty gene for 230 Chinese Han CHD patients and evaluated SNPs
rs2295418, rs360057 and g.G169A, which are located within the translated regions
of the genes. The statistical analyses were conducted using Chi-Square Tests as
implemented in SPSS (version 13.0). The Hardy-Weinberg equilibrium test of the
population was carried out using online software OEGE, and multiple-sequence
alignments of LEFTY proteins were carried out using the Vector NTI software.
RESULTS: Two heterozygous variants in Lefty1 gene, g.G169A and g.A1035C, and one
heterozygous variant in Lefty2 gene, g.C925A, were identified. Statistical
analyses showed that the rs2295418 (g.C925A) variant in Lefty2 gene was obviously
associated with the risk of CHD (P value = 0.016<0.05). The genotype frequency of
rs360057 (g.A1035C) variant in Lefty1 gene was associated with the risk of CHD (P
value = 0.007<0.05), but the allele frequency was not (P value = 0.317>0.05).
CONCLUSIONS: The SNP rs2295418 in the Lefty2 gene is associated with CHD in
Chinese Han populations.
PMID- 25111181
TI - Ecofriendly porphyrin synthesis by using water under microwave irradiation.
AB - Water, under microwave irradiation and at a temperature of 473 K, reaches
pressures above 16 bar, being capable to act as catalyst, without the use of
organic solvents and oxidants, for meso-substituted porphyrin synthesis.
Sustainability of the reaction is proved by E Factor=35 and EcoScale value of
50.5, the highest so far obtained for porphyrin synthesis. Methodology's wide
versatility is clearly demonstrated by the good yields obtained for both aryl and
alkyl substituted porphyrins. These reaction conditions represent a huge
development, not only by using very high concentrations, minimizing organic
solvent usage, but also by eradicating toxic expensive solvents and oxidants.
PMID- 25111180
TI - A splicing mutation in the novel mitochondrial protein DNAJC11 causes motor
neuron pathology associated with cristae disorganization, and lymphoid
abnormalities in mice.
AB - Mitochondrial structure and function is emerging as a major contributor to
neuromuscular disease, highlighting the need for the complete elucidation of the
underlying molecular and pathophysiological mechanisms. Following a forward
genetics approach with N-ethyl-N-nitrosourea (ENU)-mediated random mutagenesis,
we identified a novel mouse model of autosomal recessive neuromuscular disease
caused by a splice-site hypomorphic mutation in a novel gene of unknown function,
DnaJC11. Recent findings have demonstrated that DNAJC11 protein co
immunoprecipitates with proteins of the mitochondrial contact site (MICOS)
complex involved in the formation of mitochondrial cristae and cristae junctions.
Homozygous mutant mice developed locomotion defects, muscle weakness, spasticity,
limb tremor, leucopenia, thymic and splenic hypoplasia, general wasting and early
lethality. Neuropathological analysis showed severe vacuolation of the motor
neurons in the spinal cord, originating from dilatations of the endoplasmic
reticulum and notably from mitochondria that had lost their proper inner membrane
organization. The causal role of the identified mutation in DnaJC11 was verified
in rescue experiments by overexpressing the human ortholog. The full length 63
kDa isoform of human DNAJC11 was shown to localize in the periphery of the
mitochondrial outer membrane whereas putative additional isoforms displayed
differential submitochondrial localization. Moreover, we showed that DNAJC11 is
assembled in a high molecular weight complex, similarly to mitofilin and that
downregulation of mitofilin or SAM50 affected the levels of DNAJC11 in HeLa
cells. Our findings provide the first mouse mutant for a putative MICOS protein
and establish a link between DNAJC11 and neuromuscular diseases.
PMID- 25111182
TI - SpyAvidin hubs enable precise and ultrastable orthogonal nanoassembly.
AB - The capture of biotin by streptavidin is an inspiration for supramolecular
chemistry and a central tool for biological chemistry and nanotechnology, because
of the rapid and exceptionally stable interaction. However, there is no robust
orthogonal interaction to this hub, limiting the size and complexity of molecular
assemblies that can be created. Here we combined traptavidin (a streptavidin
variant maximizing biotin binding strength) with an orthogonal irreversible
interaction. SpyTag is a peptide engineered to form a spontaneous isopeptide bond
to its protein partner SpyCatcher. SpyTag or SpyCatcher was successfully fused to
the C-terminus of Dead streptavidin subunits. We were able to generate chimeric
tetramers with n (0 <= n <= 4) biotin binding sites and 4-n SpyTag or SpyCatcher
binding sites. Chimeric SpyAvidin tetramers bound precise numbers of ligands
fused to biotin or SpyTag/SpyCatcher. Mixing chimeric tetramers enabled assembly
of SpyAvidin octamers (8 subunits) or eicosamers (20 subunits). We validated
assemblies using electrophoresis and native mass spectrometry. Eicosameric
SpyAvidin was used to cluster trimeric major histocompatibility complex (MHC)
class I:beta2-microglobulin:peptide complexes, generating an assembly with up to
56 components. MHC eicosamers surpassed the conventional MHC tetramers in acting
as a powerful stimulus to T cell signaling. Combining ultrastable noncovalent
with irreversible covalent interaction, SpyAvidins enable a simple route to
create robust nanoarchitectures.
PMID- 25111183
TI - Different gDNA content in the subpopulations of prostate cancer extracellular
vesicles: apoptotic bodies, microvesicles, and exosomes.
AB - BACKGROUND: Extracellular vesicles (EVs) are cell-derived membrane vesicles. EVs
contain several RNAs such as mRNA, microRNAs, and ncRNAs, but less is known of
their genomic DNA (gDNA) content. It is also unknown whether the DNA cargo is
randomly sorted or if it is systematically packed into specific EV
subpopulations. The aim of this study was to analyze whether different prostate
cancer (PCa) cell-derived EV subpopulations (apoptotic bodies, microvesicles, and
exosomes) carry different gDNA fragments. METHODS: EV subpopulations were
isolated from three PCa cell lines (LNCaP, PC-3, and RC92a/hTERT) and the plasma
of PCa patients and healthy donors, and characterized by transmission electron
microscopy, nanoparticle tracking analysis and total protein content. gDNA
fragments of different genes were detected by real time quantitative PCR and
confirmed by DNA sequencing. RESULTS: We report that the concentration of EVs was
higher in the cancer patients than in the healthy controls. EV subpopulations
differed from each other in terms of total protein and DNA content. Analysis of
gDNA fragments of MLH1, PTEN, and TP53 genes from the PCa cell-derived EV
subpopulations showed that different EVs carried different gDNA content, which
could even harbor specific mutations. Altogether, these results suggest that both
nucleic acids and proteins are selectively and cell-dependently packed into the
EV subtypes. CONCLUSIONS: EVs derived from PCa cell lines and human plasma
samples contain double-stranded gDNA fragments which could be used to detect
specific mutations, making EVs potential biomarkers for cancer diagnostics and
prognostics.
PMID- 25111184
TI - The effect of processing on the surface physical stability of amorphous solid
dispersions.
AB - The focus of this study was to investigate the effect of processing on the
surface crystallization of amorphous molecular dispersions and gain insight into
the mechanisms underpinning this effect. The model systems, amorphous molecular
dispersions of felodipine-EUDRAGIT(r) E PO, were processed both using spin
coating (an ultra-fast solvent evaporation based method) and hot melt extrusion
(HME) (a melting based method). Amorphous solid dispersions with drug loadings of
10-90% (w/w) were obtained by both processing methods. Samples were stored under
75% RH/room temperatures for up to 10months. Surface crystallization was observed
shortly after preparation for the HME samples with high drug loadings (50-90%).
Surface crystallization was characterized by powder X-ray diffraction (PXRD), ATR
FTIR spectroscopy and imaging techniques (SEM, AFM and localized thermal
analysis). Spin coated molecular dispersions showed significantly higher surface
physical stability than hot melt extruded samples. For both systems, the progress
of the surface crystal growth followed zero order kinetics on aging. Drug
enrichment at the surfaces of HME samples on aging was observed, which may
contribute to surface crystallization of amorphous molecular dispersions. In
conclusion it was found the amorphous molecular dispersions prepared by spin
coating had a significantly higher surface physical stability than the
corresponding HME samples, which may be attributed to the increased process
related apparent drug-polymer solubility and reduced molecular mobility due to
the quenching effect caused by the rapid solvent evaporation in spin coating.
PMID- 25111186
TI - Interactive effects of contextual cues and acute alcohol intoxication on the
associations between alcohol expectancy activation and urge to drink.
AB - This study examined the joint effects of contextual cues and alcohol intoxication
on the associations between activation of positive and negative alcohol
expectancies in memory and self-reported urges to drink alcohol after a
laboratory alcohol administration. Young adult heavy drinkers were randomly
assigned to drink a moderate dose of alcohol or a placebo (alcohol manipulation),
and then listened to positive or negative drinking scenarios (cue manipulation).
Before and after these manipulations, participants completed an alcohol
expectancy Stroop task assessing positive and negative expectancy activation, as
well as self-report measures of urges to drink. Regression analyses revealed that
the alcohol and cue manipulations had a joint, moderating impact on the
associations between expectancy activation and postcue changes in urge to drink.
Specifically, both increased activation of negative expectancies and decreased
activation of positive expectancies predicted decreases in urges to drink, but
only for intoxicated participants in the negative cue condition. There were no
associations between expectancy activation and urges to drink for those in the
positive cue condition regardless of beverage condition. Results suggest that
whether memory activation of alcohol expectancies has an impact on urge to drink
after alcohol is on board may depend on the relevance of the activated
expectancies to the current drinking context. This process appears to be
influenced by a complex interaction between contextual cues in the environment
and the pharmacological effects of alcohol.
PMID- 25111185
TI - Dendritic cell-mediated, DNA-based vaccination against hepatitis C induces the
multi-epitope-specific response of humanized, HLA transgenic mice.
AB - Hepatitis C virus (HCV) is the etiologic agent of chronic liver disease,
hepatitis C. Spontaneous resolution of viral infection is associated with
vigorous HLA class I- and class II-restricted T cell responses to multiple viral
epitopes. Unfortunately, only 20% of patients clear infection spontaneously, most
develop chronic disease and require therapy. The response to chemotherapy varies,
however; therapeutic vaccination offers an additional treatment strategy. To
date, therapeutic vaccines have demonstrated only limited success. Vector
mediated vaccination with multi-epitope-expressing DNA constructs alone or in
combination with chemotherapy offers an additional treatment approach. Gene
sequences encoding validated HLA-A2- and HLA-DRB1-restricted epitopes were
synthesized and cloned into an expression vector. Dendritic cells (DCs) derived
from humanized, HLA-A2/DRB1 transgenic (donor) mice were transfected with these
multi-epitope-expressing DNA constructs. Recipient HLA-A2/DRB1 mice were
vaccinated s.c. with transfected DCs; control mice received non-transfected DCs.
Peptide-specific IFN-gamma production by splenic T cells obtained at 5 weeks post
immunization was quantified by ELISpot assay; additionally, the production of IL
4, IL-10 and TNF-alpha were quantified by cytokine bead array. Splenocytes
derived from vaccinated HLA-A2/DRB1 transgenic mice exhibited peptide-specific
cytokine production to the vast majority of the vaccine-encoded HLA class I- and
class II-restricted T cell epitopes. A multi-epitope-based HCV vaccine that
targets DCs offers an effective approach to inducing a broad immune response and
viral clearance in chronic, HCV-infected patients.
PMID- 25111187
TI - Sheet-type titania, but not P25, induced paraptosis accompanying apoptosis in
murine alveolar macrophage cells.
AB - In this study, we identified the toxic effects of sheet-type titania (TNS), which
are being developed as a material for UV-blocking glass, comparing with P25, a
benchmark control for titania, in MH-S cells, a mouse alveolar macrophage cell
line. After 24 h exposure, the TNS-exposed cells formed large vacuoles while the
P25-exposed ones did not. The decreased levels of cell viability were similar
between the P25 and TNS groups, but ATP production was clearly lower in cells
exposed to the TNS. P25 decreased the expression of calnexin protein, an
endoplasmic reticulum (ER) membrane marker, and increased the number of cells
generating ROS in a dose dependent manner. Meanwhile, TNS dilated the ER and
mitochondria and increased the secretion of NO and pro-inflammatory cytokines,
but not of ROS. Subsequently, we studied the molecular response following TNS
induced vacuolization. TNS started to form vacuoles in the cytosol since 20 min
after exposure, and the expression of the mitochondria function-related genes
were down-regulated the most in the cells exposed for 1 h. After 24 h exposure,
the number of apoptotic cells and the relative levels of BAX to Bcl-2 increased.
The expression of SOD1 protein, but not of SOD2, also dose-dependently increased
with an increase in caspase-8 activity. Additionally, the MAPK pathway was
significantly activated, even though the expression of p-EGFR did not change
significantly. Furthermore, the number of apoptotic cells increased rapidly with
time and with the inhibition of vacuole formation. Taken together, we suggest
that P25 and TNS may target different organelles. In addition, TNS, but not P25,
induced paraptosis accompanied by apoptosis in MH-S cells, and the formation of
the cytoplasmic vacuoles allowed delay apoptosis following TNS exposure.
PMID- 25111188
TI - Development of an in vitro cytochrome P450 cocktail inhibition assay for
assessing the inhibition risk of drugs of abuse.
AB - Drugs of abuse are not tested for cytochrome P450 (CYP) inhibition potential
before distribution. Therefore, a cocktail assay should be developed for testing
the inhibition potential for all relevant CYPs. The following CYP test substrates
and selective inhibitors were incubated in pooled human liver microsomes:
phenacetin (alpha-naphthoflavone for CYP1A2), coumarin (tranylcypromine, CYP2A6),
bupropion (sertraline, CYP2B6), amodiaquine (trimethoprim, CYP2C8), diclofenac
(sulfaphenazole, CYP2C9), omeprazole (fluconazole, CYP2C19), dextromethorphan
(quinidine, CYP2D6), chlorzoxazone (clomethiazole, CYP2E1), testosterone
(verapamil, CYP3A). Samples were analyzed after protein precipitation using a
Thermo Fisher Q-Exactive LC-high-resolution-MS/MS. The IC50 values were
calculated by plotting the concentration of the formed metabolite, relative to
the control sample, over the logarithm of the inhibitor concentration. They were
determined either for single substrate or the cocktail incubation. Unfortunately,
the cocktail assay had to be split because of interferences during incubation
caused by substrates or metabolites, but the mixture of both incubates could be
analyzed in one analytical run. The IC50 values determined in the single
substrate or both cocktail incubations were comparable among themselves and with
published data. In conclusion, the new inhibition cocktail assay was reproducible
and applicable for testing the inhibition potential of drugs of abuse as
exemplified for 2,5-dimethoxy-4-iodo-amfetamine (DOI).
PMID- 25111189
TI - Case studies of hydrogen sulphide occupational exposure incidents in the UK.
AB - The UK Health and Safety Executive has investigated several incidents of
workplace accidents involving hydrogen sulphide exposure in recent years.
Biological monitoring has been used in some incidents to determine the cause of
unconsciousness resulting from these incidents and as a supporting evidence in
regulatory enforcement. This paper reports on three case incidents and discusses
the use of biological monitoring in such cases. Biological monitoring has a role
in identifying hydrogen sulphide exposure in incidents, whether these are
occupational or in the wider environment. Sample type, time of collection and
sample storage are important factors in the applicability of this technique. For
non-fatal incidents, multiple urine samples are recommended at two or more time
points between the incident and 15 h post-exposure. For routine occupational
monitoring, post-shift samples should be adequate. Due to endogenous levels of
urinary thiosulphate, it is likely that exposures in excess of 12 ppm for 30 min
(or 360 ppm/min equivalent) would be detectable using biological monitoring. This
is within the Acute Exposure Guideline Level 2 (the level of the chemical in air
at or above which there may be irreversible or other serious long-lasting effects
or impaired ability to escape) for hydrogen sulphide.
PMID- 25111190
TI - COMP does not directly modify the expression of genes involved in cartilage
homeostasis in contrast to several other cartilage matrix proteins.
AB - OBJECTIVE: We investigated whether COMP may modify cartilage metabolism and play
a role as an endogenous disease aggravating factor in OA. MATERIALS AND METHODS:
Full-length and momomeric COMP was recombinantly expressed in human embryonic
kidney cells and purified it via affinity chromatography. Purified COMP was used
to stimulate either primary human chondrocytes or cartilage explants. Changes in
the expression profiles of inflammatory genes, differentiation markers and growth
factors were examined by immunoassay and by quantitative real-time reverse
transcription polymerase chain reaction. RESULTS: Incubation of primary human
chondrocytes or cartilage explants in the presence of COMP did not induce
statistically significant changes in the expression of IL-6, MMP1, MMP13,
collagen I, collagen II, collagen X, TGF-beta1 and BMP-2. CONCLUSIONS: In
contrast to collagen II and matrilin-3, COMP lacks the ability to trigger a
proinflammatory response in chondrocytes, although it carries an RGD motif and
can bind to integrins. COMP is a well-accepted biomarker for osteoarthritis but
increased COMP levels do not necessarily correlate with inflammation.
PMID- 25111191
TI - Comparison of equine articular cartilage thickness in various joints.
AB - PURPOSE: Thicknesses of fresh equine articular cartilage surfaces from the
fetlock, carpal and stifle joints were measured employing a needle probe test.
MATERIALS AND METHODS: Eighty-seven samples used in measurement were cultivated
from fetlock, carpal and stifle joints of 12 deceased within 4 h of death. After
approximately three minutes of exposure to air during dissection, all cartilage
samples were preserved in a saline solution to keep the articular cartilage
hydrated for testing. The thickness was measured on five different spots on the
same sample. The thicknesses of the fetlock, carpus and stifle were compared.
RESULTS: The articular cartilage of the stifle was thicker than the fetlock and
carpus, while the fetlock and the carpus had similar thickness values. The
average thickness of the fetlock, carpal and stifle joint are 0.86, 0.87 and 2.1
mm, respectively. They were statistically compared using the Student t-test. The
differences on the articular cartilage thicknesses between the fetlock and
stifle, and carpus and stifle were "very highly significant" (p < 0.001). This
indicates that the articular cartilage thickness of the stifle is significantly
different from that of the fetlock and carpus. Four different surfaces in the
fetlock and four in the carpal joint were also compared. Significant differences
between each set of the four surfaces were not observed. In the carpus, the
difference in thickness between the distal radius and proximal third carpal bone
articular cartilage surfaces as well as the proximal radial carpal bone and
distal radial carpal bone articular cartilage surfaces were statistically
significant.
PMID- 25111192
TI - Effect of S-methylisothiourea, an inducible nitric oxide synthase inhibitor, in
joint pain and pathology in surgically induced model of osteoarthritis.
AB - The aim of the present study was to evaluate in vivo modulatory effect of S
methylisothiourea (SMT), a preferential inhibitor of inducible nitric oxide
synthase (iNOS) on pain and pathology in the surgical model of osteoarthritis
(OA) in rats. The OA was produced by the anterior cruciate ligament transection
(ACLT) and medial meniscectomy (MMx) of right knee. SMT was administered 1 day
prior to the production of OA and continued up to day 42 postoperation.
Mechanical hyperalgesia, thermal hyperalgesia, tail flick latency after repeated
flexion and extension of OA knee and knee diameter of right knee were determined
at weekly intervals. Serum levels of IL-1beta, TNF-alpha and nitrite
concentration were determined at the end of the experiment. Glycosaminoglycan
(GAG) content, collagen content and histopathological evaluation of articular
cartilage were also determined at the end of the experiment. SMT reduced
mechanical hyperalgesia and the serum levels of IL-1beta, TNF-alpha and nitrite.
Further, SMT reduced the loss of GAG from articular cartilage. Microscopically,
SMT reduced the severity of the cartilage lesion. The results indicate the
effectiveness of SMT in attenuating the pain and pathology of experimental OA
phase by reducing the production of nitric oxide and interleukin-1beta and tumor
necrosis factor-alpha, which are known to play a major role in the
pathophysiology of OA.
PMID- 25111193
TI - Assessment of body composition in Indian adults: comparison between dual-energy X
ray absorptiometry and isotope dilution technique.
AB - Dual-energy X-ray absorptiometry (DXA) and isotope dilution technique have been
used as reference methods to validate the estimates of body composition by simple
field techniques; however, very few studies have compared these two methods. We
compared the estimates of body composition by DXA and isotope dilution (18O)
technique in apparently healthy Indian men and women (aged 19-70 years, n 152, 48
% men) with a wide range of BMI (14-40 kg/m2). Isotopic enrichment was assessed
by isotope ratio mass spectroscopy. The agreement between the estimates of body
composition measured by the two techniques was assessed by the Bland-Altman
method. The mean age and BMI were 37 (sd 15) years and 23.3 (sd 5.1) kg/m2,
respectively, for men and 37 (sd 14) years and 24.1 (sd 5.8) kg/m2, respectively,
for women. The estimates of fat-free mass were higher by about 7 (95 % CI 6, 9)
%, those of fat mass were lower by about 21 (95 % CI - 18, - 23) %, and those of
body fat percentage (BF%) were lower by about 7.4 (95 % CI - 8.2, - 6.6) % as
obtained by DXA compared with the isotope dilution technique. The Bland-Altman
analysis showed wide limits of agreement that indicated poor agreement between
the methods. The bias in the estimates of BF% was higher at the lower values of
BF%. Thus, the two commonly used reference methods showed substantial differences
in the estimates of body composition with wide limits of agreement. As the
estimates of body composition are method-dependent, the two methods cannot be
used interchangeably.
PMID- 25111196
TI - Nonsterile glove use in addition to hand hygiene to prevent late-onset infection
in preterm infants: randomized clinical trial.
AB - IMPORTANCE: Late-onset infections commonly occur in extremely preterm infants and
are associated with high rates of mortality and neurodevelopmental impairment.
Hand hygiene alone does not always achieve the desired clean hands, as
microorganisms are still present more than 50% of the time. We hypothesize that
glove use after hand hygiene may further decrease these infections. OBJECTIVE: To
determine if nonsterile glove use after hand hygiene before all patient and
intravenous catheter contact, compared with hand hygiene alone, prevents late
onset infections in preterm infants. DESIGN, SETTINGS, AND PARTICIPANTS: A
prospective, single-center, clinical, randomized trial was conducted in infants
admitted to the neonatal intensive care unit who weighed less than 1000 g and/or
had a gestational age of less than 29 weeks and were less than 8 days old. There
were 175 eligible infants, of which 120 were enrolled during a 30-month period
from December 8, 2008, to June 20, 2011. INTERVENTIONS: Infants were randomly
assigned to receive care with nonsterile gloves after hand hygiene (group A) or
care after hand hygiene alone (group B) before all patient and intravenous line
(central and peripheral) contact. Study intervention was continued while patients
had central or peripheral venous access. MAIN OUTCOMES AND MEASURES: One or more
episodes of late-onset (>72 hours of age) infection in the bloodstream, urinary
tract, or cerebrospinal fluid or necrotizing enterocolitis. RESULTS: The 2 groups
were similar in baseline demographic characteristics. Late-onset invasive
infection or necrotizing enterocolitis occurred in 32% of infants (19 of 60) in
group A compared with 45% of infants (27 of 60) in group B (difference, -12%; 95%
CI, -28% to 6%; P = .13). In group A compared with group B, there were 53% fewer
gram-positive bloodstream infections (15% [9 of 60] vs 32% [19 of 60];
difference, -17%; 95% CI, -31% to -1%; P = .03) and 64% fewer central line
associated bloodstream infections (3.4 vs 9.4 per 1000 central line days; ratio,
0.36; 95% CI, 0.16 to 0.81; P = .01). CONCLUSIONS AND RELEVANCE: Glove use after
hand hygiene prior to patient and line contact is associated with fewer gram
positive bloodstream infections and possible central line-associated bloodstream
infections in preterm infants. This readily implementable infection control
measure may result in decreased infections in high-risk preterm infants. TRIAL
REGISTRATION: clinicaltrials.gov Identifier: NCT01729000.
PMID- 25111195
TI - Extremely low-frequency electromagnetic fields cause G1 phase arrest through the
activation of the ATM-Chk2-p21 pathway.
AB - In daily life, humans are exposed to the extremely low-frequency electromagnetic
fields (ELF-EMFs) generated by electric appliances, and public concern is
increasing regarding the biological effects of such exposure. Numerous studies
have yielded inconsistent results regarding the biological effects of ELF-EMF
exposure. Here we show that ELF-EMFs activate the ATM-Chk2-p21 pathway in HaCaT
cells, inhibiting cell proliferation. To present well-founded results, we
comprehensively evaluated the biological effects of ELF-EMFs at the
transcriptional, protein, and cellular levels. Human HaCaT cells from an
immortalized epidermal keratinocyte cell line were exposed to a 1.5 mT, 60 Hz ELF
EMF for 144 h. The ELF-EMF could cause G1 arrest and decrease colony formation.
Protein expression experiments revealed that ELF-EMFs induced the activation of
the ATM/Chk2 signaling cascades. In addition, the p21 protein, a regulator of
cell cycle progression at G1 and G2/M, exhibited a higher level of expression in
exposed HaCaT cells compared with the expression of sham-exposed cells. The ELF
EMF-induced G1 arrest was diminished when the CHK2 gene expression (which encodes
checkpoint kinase 2; Chk2) was suppressed by specific small interfering RNA
(siRNA). These findings indicate that ELF-EMFs activate the ATM-Chk2-p21 pathway
in HaCaT cells, resulting in cell cycle arrest at the G1 phase. Based on the
precise control of the ELF-EMF exposure and rigorous sham-exposure experiments,
all transcriptional, protein, and cellular level experiments consistently
supported the conclusion. This is the first study to confirm that a specific
pathway is triggered by ELF-EMF exposure.
PMID- 25111197
TI - Control of single-molecule junction conductance of porphyrins via a transition
metal center.
AB - Using scanning tunneling microscope break-junction experiments and a new first
principles approach to conductance calculations, we report and explain low-bias
charge transport behavior of four types of metal-porphyrin-gold molecular
junctions. A nonequilibrium Green's function approach based on self-energy
corrected density functional theory and optimally tuned range-separated hybrid
functionals is developed and used to understand experimental trends
quantitatively. Importantly, due to the localized d states of the porphyrin
molecules, hybrid functionals are essential for explaining measurements; standard
semilocal functionals yield qualitatively incorrect results. Comparing directly
with experiments, we show that the conductance can change by nearly a factor of 2
when different metal cations are used, counter to trends expected from gas-phase
ionization energies which are relatively unchanged with the metal center. Our
work explains the sensitivity of the porphyrin conductance with the metal center
via a detailed and quantitative portrait of the interface electronic structure
and provides a new framework for understanding transport quantitatively in
complex junctions involving molecules with localized d states of relevance to
light harvesting and energy conversion.
PMID- 25111198
TI - Manganese doped fluorescent paramagnetic nanocrystals for dual-modal imaging.
AB - In this work, dual-modal (fluorescence and magnetic resonance) imaging
capabilities of water-soluble, low-toxicity, monodisperse Mn-doped ZnSe
nanocrystals (NCs) with a size (6.5 nm) below the optimum kidney cutoff limit (10
nm) are reported. Synthesizing Mn-doped ZnSe NCs with varying Mn(2+)
concentrations, a systematic investigation of the optical properties of these NCs
by using photoluminescence (PL) and time resolved fluorescence are demonstrated.
The elemental properties of these NCs using X-ray photoelectron spectroscopy and
inductive coupled plasma-mass spectroscopy confirming Mn(2+) doping is confined
to the core of these NCs are also presented. It is observed that with increasing
Mn(2+) concentration the PL intensity first increases, reaching a maximum at
Mn(2+) concentration of 3.2 at% (achieving a PL quantum yield (QY) of 37%), after
which it starts to decrease. Here, this high-efficiency sample is demonstrated
for applications in dual-modal imaging. These NCs are further made water-soluble
by ligand exchange using 3-mercaptopropionic acid, preserving their PL QY as high
as 18%. At the same time, these NCs exhibit high relaxivity (~2.95 mM(-1) s(-1))
to obtain MR contrast at 25 degrees C, 3 T. Therefore, the Mn(2+) doping in
these water-soluble Cd-free NCs are sufficient to produce contrast for both
fluorescence and magnetic resonance imaging techniques.
PMID- 25111199
TI - Docetaxel plus oral metronomic cyclophosphamide: a phase II study with
pharmacodynamic and pharmacogenetic analyses in castration-resistant prostate
cancer patients.
AB - BACKGROUND: Docetaxel plus prednisone is currently the standard first-line
treatment in metastatic castration-resistant prostate cancer (mCRPC). The aim of
this study was to assess the clinical activity and
pharmacodynamic/pharmacogenetic profile of docetaxel plus prednisone in
combination with metronomic cyclophosphamide in mCRPC patients. METHODS: Forty
one chemotherapy-naive patients received docetaxel (60 mg/m(2) intravenously
every 3 weeks up to 12 cycles) and, from day 2, prednisone 10 mg/day, celecoxib
400 mg/day, and metronomic cyclophosphamide 50 mg/day, continuously. Plasma VEGF
and bFGF were detected by ELISA. Real-time PCR-SNP analysis of VEGF gene was
performed using an ABI PRISM 7900HT SDS and TaqMan SNP genotyping. RESULTS:
Eighty-seven percent of patients were free of progression at 6 months. A decrease
in prostate-specific antigen >=50% was observed in 82% of 39 evaluable patients,
with a median time to progression of 12.3 months. Grade 3 adverse events were
neutropenia (5%), thrombocytopenia, diarrhea, and stomatitis (2.5%). Median PFS
and OS were 14.9 months (95% CI, 9.2-15.3 months) and 33.3 months (95% CI, 23
35.6 months), respectively. Of 11 patients (28%) with evaluable disease, 5 (44%)
achieved a complete response, 2 (11%) a partial response, and 2 (11%) stable
disease, whereas 2 showed disease progression. The -1154A/G VEGF polymorphism,
plasma VEGF, and bFGF after the first cycle of chemotherapy may represent useful
pharmacodynamic markers to predict better outcomes. CONCLUSIONS: The combination
of docetaxel and oral metronomic chemotherapy is effective and well tolerated in
mCRPC patients and may deserve further evaluation.
PMID- 25111200
TI - Stroke code improves intravenous thrombolysis administration in acute ischemic
stroke.
AB - BACKGROUND AND PURPOSE: Timely intravenous (IV) thrombolysis for acute ischemic
stroke is associated with better clinical outcomes. Acute stroke care implemented
with "Stroke Code" (SC) may increase IV tissue plasminogen activator (tPA)
administration. The present study aimed to investigate the impact of SC on
thrombolysis. METHODS: The study period was divided into the "pre-SC era"
(January 2006 to July 2010) and "SC era" (August 2010 to July 2013).
Demographics, critical times (stroke symptom onset, presentation to the emergency
department, neuroimaging, thrombolysis), stroke severity, and clinical outcomes
were recorded and compared between the two eras. RESULTS: During the study
period, 5957 patients with acute ischemic stroke were admitted; of these, 1301
(21.8%) arrived at the emergency department within 3 h of stroke onset and 307
(5.2%) received IV-tPA. The number and frequency of IV-tPA treatments for
patients with an onset-to-door time of <3 h increased from the pre-SC era (n =
91, 13.9%) to the SC era (n = 216, 33.3%) (P<0.001). SC also improved the
efficiency of IV-tPA administration; the median door-to-needle time decreased (88
to 51 min, P<0.001) and the percentage of door-to-needle times <=60 min increased
(14.3% to 71.3%, P<0.001). The SC era group tended to have more patients with
good outcome (modified Rankin Scale <=2) at discharge (49.5 vs. 39.6%, P = 0.11),
with no difference in symptomatic hemorrhage events or in-hospital mortality.
CONCLUSION: The SC protocol increases the percentage of acute ischemic stroke
patients receiving IV-tPA and decreases door-to-needle time.
PMID- 25111201
TI - IgY pharmacokinetics in rabbits: implications for IgY use as antivenoms.
AB - This paper presents the first study of chicken IgY pharmacokinetics (PK) in
rabbits. We measured IgY blood serum concentrations using a specific high
sensitivity ELISA method. The fast initial component observed when studying horse
Fab, F(ab')2 or IgG was absent from IgY PK. During the first 80 min of
observation there was only a single slow exponential decay, which sped up
afterward to the point that IgY became undetectable after 216 h of observation;
due to this time course, PK parameters were determined with trapezoidal
integration. The most significant IgY pharmacokinetic parameters determined were
(all presented as medians and their 95% confidence interval): Area Under the
Curve = 183.8 (135.2, 221.5) mg.h.L(-1); Distribution volume of the central
compartment.[Body Weight (BW)](-1) = 46.0 (21.7, 70.3) mL.kg(-1); Distribution
volume in steady state.BW(-1) = 56.8 (44.4, 68.5) mLkg(-1); Mean Residence Time =
40.1 (33.6, 48.5) h; Total plasma clearance.BW(-1) = 1.44 (1.15, 1.66) mL.h(
1).kg(-1). Anti IgY IgG titers determined by ELISA increased steadily after 72 h,
and reached 2560 (1920, 5760) dilution(-1) at 264 h; anti-chicken IgG
concentrations rose up to 3.19 (2.31, 6.17) MUg/mL in 264 h. Our results show
that IgY PK lacks the fast initial decay observed in other PK studies using horse
IgG, F(ab')2 or Fab, remains in the body 39.0 (28.7, 47.2) % much as IgG and is
~3 times more immunogenic that horse IgG in rabbits.
PMID- 25111202
TI - Kinetics and mechanism of the racemization of aryl allenes catalyzed by cationic
gold(I) phosphine complexes.
AB - The kinetics of the racemization of aromatic 1,3-disubstituted allenes catalyzed
by gold phosphine complexes has been investigated. The rate of gold-catalyzed
allene racemization displayed first-order dependence on allene, and catalyst
concentration and kinetic analysis of gold-catalyzed allene racemization as a
function of allene and phosphine electron-donor ability established the
accumulation of electron density on the phosphine atom and the depletion of
electron density on the terminal allenyl carbon atoms in the rate-limiting
transition state for racemization. These and other observations were in accord
with a mechanism for allene racemization involving rapid and reversible inter-
and intramolecular allene exchange followed by turnover-limiting, unimolecular
conversion of a chiral gold eta(2)-allene complex to an achiral eta(1)-allylic
cation intermediate through a bent and twisted eta(1)-allene transition state.
With respect to proper ligand selection, these studies reveal that both electron
poor phosphine ligands and polar solvents facilitate racemization.
PMID- 25111206
TI - Alzheimer disease risk factors.
PMID- 25111207
TI - Alzheimer disease risk factors--reply.
PMID- 25111208
TI - GNAL mutations and dystonia.
PMID- 25111209
TI - GNAL mutations and dystonia--reply.
PMID- 25111210
TI - Blood test for variant Creutzfeldt-Jakob disease.
PMID- 25111211
TI - Blood test for variant Creutzfeldt-Jakob disease--reply.
PMID- 25111212
TI - Elevated serum DDE and risk for Alzheimer disease.
PMID- 25111213
TI - Defining the new end point for multiple sclerosis treatment.
PMID- 25111214
TI - Elevated serum DDE and risk for Alzheimer disease--reply.
PMID- 25111217
TI - Pregnancy post-laparoscopic hysteropexy.
PMID- 25111218
TI - Impact of the anesthetic conserving device on respiratory parameters and work of
breathing in critically ill patients under light sedation with sevoflurane.
AB - BACKGROUND: Sevoflurane sedation in the intensive care unit is possible with a
special heat and moisture exchanger called the Anesthetic Conserving Device (ACD)
(AnaConDa; Sedana Medical AB, Uppsala, Sweden). The ACD, however, may corrupt
ventilatory mechanics when used during the weaning process of intensive care unit
patients. The authors compared the ventilatory effects of light-sedation with
sevoflurane administered with the ACD and those of classic management, consisting
of a heated humidifier and intravenous sedation, in intensive care unit patients
receiving pressure-support ventilation. METHODS: Fifteen intensive care unit
patients without chronic pulmonary disease were included. A target Richmond
Agitation Sedation Scale level of -1/-2 was obtained with intravenous
remifentanil (baseline 1-condition). Two successive interventions were tested:
replacement of the heated humidifier by the ACD without sedation change (ACD
condition) and sevoflurane with the ACD with an identical target level (ACD
sevoflurane-condition). Patients finally returned to baseline (baseline 2
condition). Work of breathing, ventilatory patterns, blood gases, and tolerance
were recorded. A steady state of 30 min was achieved for each experimental
condition. RESULTS: ACD alone worsened ventilatory parameters, with significant
increases in work of breathing (from 1.7 +/- 1.1 to 2.3 +/- 1.2 J/l), minute
ventilation, P0,1, intrinsic positive end-expiratory pressure (from 1.3 +/- 2.6
to 4.7 +/- 4.2 cm H2O), inspiratory pressure swings, and decreased patient
comfort. Sevoflurane normalized work of breathing (from 2.3 +/- 1.2 to 1.8 +/- 1
J/l), intrinsic positive end-expiratory pressure (from 4.7 +/- 4.2 to 1.8 +/- 2
cm H2O), inspiratory pressure swings, other ventilatory parameters, and patient
tolerance. CONCLUSIONS: ACD increases work of breathing and worsens ventilatory
parameters. Sevoflurane use via the ACD (for a light-sedation target) normalizes
respiratory parameters. In this patient's population, light-sedation with
sevoflurane and the ACD may be possible during the weaning process.
PMID- 25111219
TI - Development and validation of instrumentation to assess perceptions of
educational issues for students with cancer.
PMID- 25111220
TI - Microvillous atrophy: atypical presentations.
AB - OBJECTIVES: Microvillous inclusion disease (MVID) is a cause of intractable
diarrhea in infancy. In its classic form, the disease is characterized by a
severe persistent watery diarrhea starting within the first days of life.
Parenteral nutrition and small bowel transplantation are the only known
treatments for the affected children. Histologically, periodic acid-Schiff (PAS)
staining shows accumulation of periodic acid-Schiff-positive staining material
along the apical pole of enterocytes, whereas transmission electron microscopy
exhibits microvillus inclusion bodies within the cytoplasm of enterocytes with
rarefied and shortened microvilli and secretory granules. The objective of this
work was to explore clinical, morphological, and genetic findings in cases of
MVID with unusual presentations. METHODS: Clinical, histological, and genetic
findings are reported for 8 cases of MVID with atypical presentation. RESULTS:
The diarrhea started after several months in 3 cases. It was usually less
abundant and 3 patients were weaned off parenteral nutrition. None required
intestinal transplantation. Three patients experienced malformations, dysmorphy,
sensory disabilities, and severe mental retardation. One had a hydrocephaly.
Three patients had a cholestasis with low gamma-glutamyl transferase levels.
Light microscopy showed histological abnormalities consistent with MVID in all of
the cases, but the lesions were sometimes focal or delayed. Transmission electron
microscopy retrieved some criteria of MVID in 4 patients. Finally, 6 patients
were homozygotes or compound heterozygotes for MYO5B mutations. CONCLUSIONS: This
study extends the spectrum of MVID to less severe clinical presentations.
PMID- 25111221
TI - Breast-feeding improves gut maturation compared with formula feeding in preterm
babies.
AB - OBJECTIVE: The incidence of necrotizing enterocolitis (NEC) is higher in formula
fed babies than in breast-fed babies, which may be caused by breast-feeding
induced gut maturation. The effect of breast-feeding on gut maturation has been
widely studied in animal models. This study aimed to assess the effects of breast
feeding on intestinal maturation in prematurely born babies by evaluating
postnatal changes in urinary intestinal fatty acid binding protein (I-FABP)
levels, a specific enterocyte marker. METHODS: Gut maturation in 40 premature
babies (<37 weeks of gestation) without gastrointestinal morbidity was studied,
of whom 21 were exclusively breast-fed and 19 were formula-fed infants. Urinary I
FABP levels as the measure of gut maturation were measured at 5, 12, 19, and 26
days after birth. RESULTS: In breast-fed infants, there was a significant
increase in median urinary I-FABP levels between 5 and 12 days after birth (104
[78-340] pg/mL to 408 [173-1028] pg/mL, P = 0.002), whereas I-FABP concentration
in formula-fed infants increased between 12 and 19 days after birth (105 [44-557]
pg/mL, 723 [103-1670] pg/mL, P = 0.004). Breast-fed babies had significantly
higher median urinary I-FABP levels at postnatal day 12 (P = 0.01). CONCLUSIONS:
The time course of the postnatal increase in urinary I-FABP levels reflecting gut
maturation was significantly delayed in formula-fed babies, suggesting a delayed
physiological response in formula-fed compared with breast-fed infants.
PMID- 25111222
TI - Inflammatory bowel disease in children of Manitoba: 30 years' experience of a
tertiary center.
AB - OBJECTIVES: The aim of this study was to describe the incidence and prevalence of
inflammatory bowel disease (IBD) in children <17 years of age in 30 years from
1978 to 2007. METHODS: From January 1, 1978, to December 31, 2007, the sex- and
age-adjusted annual incidence and prevalence of pediatric IBD per 100,000
population were calculated based on the pediatric IBD database of the only
pediatric tertiary center in the province. The annual health statistics records
for the Province of Manitoba were used to calculate population estimates for the
participants. To ensure validity of data, the University of Manitoba IBD
Epidemiology Database was analyzed for patients <17 years of age from 1989 to
2000. RESULTS: The sex- and age-adjusted incidence of pediatric Crohn disease has
increased from 1.2/100,000 in 1978 to 4.68/100,000 in 2007 (P < 0.001). For
ulcerative colitis, the incidence has increased from 0.47/100,000 in 1978 to
1.64/100,000 in 2007 (P < 0.001). During the same time period, the prevalence of
Crohn disease has increased from 3.1 to 18.9/100,000 (P < 0.001) and from 0.7 to
12.7/100,000 for ulcerative colitis (P < 0.001). During the last 5 years of the
study the average annual incidence of IBD in urban patients was 8.69/100,000 as
compared with 4.75/100,000 for rural patients (P < 0.001). CONCLUSIONS: The
incidence and prevalence of pediatric IBD are increasing. The majority of
patients were residents of urban Manitoba, confirming the important role of
environmental factors in the etiopathogenesis of IBD.
PMID- 25111223
TI - A 16-Year-Old Boy With Colonic Adenocarcinoma.
PMID- 25111224
TI - Psychometric properties of PedsQL generic core scales for children with
functional constipation in the Netherlands.
AB - OBJECTIVES: The aim of the study was to evaluate the psychometric properties of
the Dutch translation of the Pediatric Quality of Life Inventory version 4.0
Generic Core Scales (PedsQL) in children with functional constipation (FC).
METHODS: The PedsQL was completed by children with FC ages 5 to 18 years and by
the parents of children ages 2 to 18 years. To assess construct validity, all of
the parents and children completed the PedsQL Gastrointestinal Symptoms Module
(GI module) and children ages 8 to 18 years completed the defecation disorder
list. Item response distributions, internal consistency reliability, patient
parent agreement, and discriminating ability were evaluated. RESULTS: Overall,
269 children were enrolled. The PedsQL showed minimal missing responses (self
report: 5.3% with >50% missing, parent report: 2.6% with >50% missing) and
achieved satisfactory internal consistency for the total (self-report: alpha =
0.86, parent report: alpha = 0.88), physical health (self-report: alpha = 0.75,
parent report alpha = 0.83), and psychosocial health (self-report: alpha = 0.80;
parent report: alpha = 0.85) scores. Internal consistency was less convincing for
those ages 5 to 7 years (alpha = 0.53-0.77) than for older individuals. Self
reported health-related quality of life was lower than parent reported, with the
exception of children ages 5 to 7 years. Interrater reliability intraclass
correlations were 0.52 to 0.61 for the overall population. Correlations among the
PedsQL, GI module, and defecation disorder list were consistent with a priori
hypotheses and generally supported construct validity. The PedsQL distinguished
between a previously published healthy reference sample and children with FC, and
between those with mild and severe symptoms (P < 0.05). CONCLUSIONS: The self
reported and proxy reported PedsQL demonstrated satisfactory measurement
properties in Dutch children with FC ages 8 to 18 years. Further research is
needed to establish internal consistency and validity in those ages 5 to 7 years.
PMID- 25111225
TI - Scanning the scars: the utility of transient elastography in young children.
PMID- 25111226
TI - Thrombospondin-1 deficiency causes a shift from fibroproliferative to
inflammatory kidney disease and delays onset of renal failure.
AB - Thrombospondin-1 (TSP1) is a multifunctional matricellular protein known to
promote progression of chronic kidney disease. To gain insight into the
underlying mechanisms through which TSP1 accelerates chronic kidney disease, we
compared disease progression in Col4a3 knockout (KO) mice, which develop
spontaneous kidney failure, with that of Col4a3;Tsp1 double-knockout (DKO) mice.
Decline of excretory renal function was significantly delayed in the absence of
TSP1. Although Col4a3;Tsp1 DKO mice did progress toward end-stage renal failure,
their kidneys exhibited distinct histopathological lesions, compared with
creatinine level-matched Col4a3 KO mice. Although kidneys of both Col4a3 KO and
Col4a3;Tsp1 DKO mice exhibited a widened tubulointerstitium, predominant lesions
in Col4a3 KO kidneys were collagen deposition and fibroblast accumulation,
whereas in Col4a3;Tsp1 DKO kidney inflammation was predominant, with less
collagen deposition. Altered disease progression correlated with impaired
activation of transforming growth factor-beta1 (TGF-beta1) in vivo and in vitro
in the absence of TSP1. In summary, our findings suggest that TSP1 contributes to
progression of chronic kidney disease by catalyzing activation of latent TGF
beta1, resulting in promotion of a fibroproliferative response over an
inflammatory response. Furthermore, the findings suggest that fibroproliferative
and inflammatory lesions are independent entities, both of which contribute to
decline of renal function.
PMID- 25111227
TI - Mutations in pre-mRNA processing factors 3, 8, and 31 cause dysfunction of the
retinal pigment epithelium.
AB - Mutations in the ubiquitously expressed pre-mRNA processing factors 3, 8, and 31
(PRPF3, PRPF8, and PRPF31) cause nonsyndromic dominant retinitis pigmentosa in
humans, an inherited retinal degeneration. It is unclear what mechanisms, or
which cell types of the retina, are affected. Transgenic mice with the human
mutations in these genes display late-onset morphological changes in the retinal
pigment epithelium (RPE). To determine whether the observed morphological changes
are preceded by abnormal RPE function, we investigated its phagocytic function in
Prpf3(T494M/T494M), Prpf8(H2309P/H2309P), and Prpf31(+/-) mice. We observe
decreased phagocytosis in primary RPE cultures from mutant mice, and this is
replicated by shRNA-mediated knockdown of PRPF31 in human ARPE-19 cells. The
diurnal rhythmicity of phagocytosis is almost lost, indicated by the marked
attenuation of the phagocytic burst 2 hours after light onset. The strength of
adhesion between RPE apical microvilli and photoreceptor outer segments also
declined during peak adhesion in all mutants. In all models, at least one of the
receptors involved in binding and internalization of shed photoreceptor outer
segments was subjected to changes in localization. Although the mechanism
underlying these changes in RPE function is yet to be elucidated, these data are
consistent with the mouse RPE being the primary cell affected by mutations in the
RNA splicing factors, and these changes occur at an early age.
PMID- 25111228
TI - Silencing of drpr leads to muscle and brain degeneration in adult Drosophila.
AB - Mutations in the gene encoding the single transmembrane receptor multiple
epidermal growth factor-like domain 10 (MEGF10) cause an autosomal recessive
congenital muscle disease in humans. Although mammalian MEGF10 is expressed in
the central nervous system as well as in skeletal muscle, patients carrying
mutations in MEGF10 do not show symptoms of central nervous system dysfunction.
drpr is the sole Drosophila homolog of the human genes MEGF10, MEGF11, and MEGF12
(JEDI, PEAR). The functional domains of MEGF10 and drpr bear striking
similarities, and residues affected by MEGF10 mutations in humans are conserved
in drpr. Our analysis of drpr mutant flies revealed muscle degeneration with
fiber size variability and vacuolization, as well as reduced motor performance,
features that have been observed in human MEGF10 myopathy. Vacuolization was also
seen in the brain. Tissue-specific RNAi experiments demonstrated that drpr
deficiency in muscle, but not in the brain, leads to locomotor defects. The
histological and behavioral abnormalities seen in the affected flies set the
stage for further studies examining the signaling pathway modulated by
MEGF10/Drpr in muscle, as well as assessing the effects of genetic and/or
pharmacological manipulations on the observed muscle defects. In addition, the
absence of functional redundancy for Drpr in Drosophila may help elucidate
whether paralogs of MEGF10 in humans (eg, MEGF11) contribute to maintaining wild
type function in the human brain.
PMID- 25111229
TI - CREB-induced inflammation is important for malignant mesothelioma growth.
AB - Malignant mesothelioma (MM) is an aggressive tumor with no treatment regimen.
Previously we have demonstrated that cyclic AMP response element binding protein
(CREB) is constitutively activated in MM tumor cells and tissues and plays an
important role in MM pathogenesis. To understand the role of CREB in MM tumor
growth, we generated CREB-inhibited MM cell lines and performed in vitro and in
vivo experiments. In vitro experiments demonstrated that CREB inhibition results
in significant attenuation of proliferation and drug resistance of MM cells. CREB
silenced MM cells were then injected into severe combined immunodeficiency mice,
and tumor growth in s.c. and i.p. models of MM was followed. We observed
significant inhibition in MM tumor growth in both s.c. and i.p. models and the
presence of a chemotherapeutic drug, doxorubicin, further inhibited MM tumor
growth in the i.p. model. Peritoneal lavage fluids from CREB-inhibited tumor
bearing mice showed a significantly reduced total cell number, differential cell
counts, and pro-inflammatory cytokines and chemokines (IL-6, IL-8, regulated on
activation normal T cell expressed and secreted, monocyte chemotactic protein-1,
and vascular endothelial growth factor). In vitro studies showed that asbestos
induced inflammasome/inflammation activation in mesothelial cells was CREB
dependent, further supporting the role of CREB in inflammation-induced MM
pathogenesis. In conclusion, our data demonstrate the involvement of CREB in the
regulation of MM pathogenesis by regulation of inflammation.
PMID- 25111230
TI - Sphingosine-1-phosphate mediates a reciprocal signaling pathway between stellate
cells and cancer cells that promotes pancreatic cancer growth.
AB - Sphingosine-1-phosphate (S1P) is produced by sphingosine kinase 1 and is
implicated in tumor growth, although the mechanisms remain incompletely
understood. Pancreatic stellate cells (PSCs) reside within the tumor
microenvironment and may regulate tumor progression. We hypothesized that S1P
activates PSCs to release paracrine factors, which, in turn, increase cancer cell
invasion and growth. We used a combination of human tissue, in vitro, and in vivo
studies to mechanistically evaluate this concept. Sphingosine kinase 1 was
overexpressed in human pancreatic tissue, especially within tumor cells. S1P
activated PSCs in vitro and conditioned medium from S1P-stimulated PSCs,
increased pancreatic cancer cell migration, and invasion, which was dependent on
S1P2, ABL1 (alias c-Abl) kinase, and matrix metalloproteinase-9. In vivo studies
showed that pancreatic cancer cells co-implanted with S1P2 receptor knockdown
PSCs led to less cancer growth and metastasis in s.c. and orthotopic pancreatic
cancer models compared with control PSCs. Pancreatic cancer cell-derived S1P
activates PSCs to release paracrine factors, including matrix metalloproteinase
9, which reciprocally promotes tumor cell migration and invasion in vitro and
cancer growth in vivo.
PMID- 25111231
TI - Comparative urease enzyme inhibition profile of leaves and stems of Rumex
nervosus vahl.
AB - Ureases inhibitory agents are becoming important because of their application in
treating many aliments. This work describes the urease inhibitory potential of
the crude extracts of leaves and stems of Rumex nervosus, which includes crude
extracts as well as various sub-fractions, n-hexane, chloroform, ethyl acetate
and methanol. The crude extracts of stems and leaves exhibited promising ureases
inhibition (IC50 values of 17.5 +/- 0.84 and 29.6 +/- 0.96 MUg/mL, respectively).
Among the sub-fractions, methanol-soluble fractions of leaves and stems showed
significant inhibition having IC50 values of 21.9 +/- 0.67 and 21.5 +/- 0.69
MUg/mL, respectively, followed by ethyl acetate fractions of stems and leaves.
PMID- 25111233
TI - Psychological stress increases risk for peptic ulcer, regardless of Helicobacter
pylori infection or use of nonsteroidal anti-inflammatory drugs.
AB - BACKGROUND & AIMS: There is controversy over whether psychological stress
contributes to development of peptic ulcers. We collected data on features of
life stress and ulcer risk factors from a defined population in Denmark and
compared these with findings of confirmed ulcers during the next 11-12 years.
METHODS: We collected blood samples and psychological, social, behavioral, and
medical data in 1982-1983 from a population-based sample of 3379 Danish adults
without a history of ulcer participating in the World Health Organization's
MONICA study. A 0- to 10-point stress index scale was used to measure stress on
the basis of concrete life stressors and perceived distress. Surviving eligible
participants were reinterviewed in 1987-1988 (n = 2809) and 1993-1994 (n = 2410).
Ulcer was diagnosed only for patients with a distinct breach in the mucosa. All
diagnoses were confirmed by review of radiologic and endoscopic reports.
Additional cases of ulcer were detected in a search of all 3379 subjects in the
Danish National Patient Register. RESULTS: Seventy-six subjects were diagnosed
with ulcer. On the basis of the stress index scale, ulcer incidence was
significantly higher among subjects in the highest tertile of stress scores
(3.5%) than the lowest tertile (1.6%) (adjusted odds ratio, 2.2; 95% confidence
interval [CI], 1.2-3.9; P < .01). The per-point odds ratio for the stress index
(1.19; 95% CI, 1.09-1.31; P < .001) was unaffected after adjusting for the
presence of immunoglobulin G antibodies against Helicobacter pylori in stored
sera, alcohol consumption, or sleep duration but lower after adjusting for
socioeconomic status (1.17; 95% CI, 1.07-1.29; P < .001) and still lower after
further adjustments for smoking, use of nonsteroidal anti-inflammatory drugs, and
lack of exercise (1.11; 95% CI, 1.01-1.23; P = .04). The risk for ulcer related
to stress was similar among subjects who were H pylori seropositive, those who
were H pylori seronegative, and those exposed to neither H pylori nor
nonsteroidal anti-inflammatory drugs. On multivariable analysis, stress,
socioeconomic status, smoking, H pylori infection, and use of nonsteroidal anti
inflammatory drugs were independent predictors of ulcer. CONCLUSIONS: In a
prospective study of a population-based Danish cohort, psychological stress
increased the incidence of peptic ulcer, in part by influencing health risk
behaviors. Stress had similar effects on ulcers associated with H pylori
infection and those unrelated to either H pylori or use of nonsteroidal anti
inflammatory drugs.
PMID- 25111232
TI - Comparative molecular dynamics simulation of Hepatitis C Virus NS3/4A protease
(Genotypes 1b, 3a and 4b) predicts conformational instability of the catalytic
triad in drug resistant strains.
AB - The protease domain of the Hepatitis C Virus (HCV) nonstructural protein 3 (NS3)
has been targeted for inhibition by several direct-acting antiviral drugs. This
approach has had marked success to treat infections caused by HCV genotype 1
predominant in the USA, Europe, and Japan. However, genotypes 3 and 4, dominant
in developing countries, are resistant to a number of these drugs and little
progress has been made towards understanding the structural basis of their drug
resistivity. We have previously developed a 4D computational methodology, based
on 3D structure modeling and molecular dynamics simulation, to analyze the active
sites of the NS3 proteases of HCV-1b and 4a in relation to their catalytic
activity and drug susceptibility. Here, we improved the methodology, extended the
analysis to include genotype 3a (predominant in South Asia including Pakistan),
and compared the results of the three genotypes (1b, 3a and 4a). The 4D analyses
of the interactions between the catalytic triad residues (His57, Asp81, and
Ser139) indicate conformational instability of the catalytic site in HCV-3a and
4a compared to that of HCV-1b NS3 protease. The divergence is gradual and
genotype-dependent, with HCV-1b being the most stable, HCV-4a being the most
unstable and HCV-3a representing an intermediate state. These results suggest
that the structural dynamics behavior, more than the rigid structure, could be
related to the altered catalytic activity and drug susceptibility seen in NS3
proteases of HCV-3a and 4a.
PMID- 25111235
TI - Training directors have positive perceptions of a competency-based
gastroenterology and transplant hepatology fellowship program.
AB - BACKGROUND & AIMS: In 2012, the American Board of Internal Medicine approved a
pilot competency-based transplant hepatology (TH) training program. This program
allows gastroenterology (GI) and TH fellowships to be completed in 3 years. We
investigated the perceptions and beliefs of GI and TH division and fellowship
program directors on the competency-based TH training program. METHODS: All
current GI and TH division and fellowship program directors from the 162
fellowship programs accredited by the Accreditation Council for Graduate Medical
Education were invited via e-mail to anonymously complete the online survey. The
survey questioned their perceptions of the 3-year combined GI and TH training
program. RESULTS: A total of 116 participants completed the survey (~38% response
rate). Most respondents were GI fellowship directors (61%); 15% were GI and
hepatology division directors, 19% were TH fellowship directors, 14% were TH
division directors, and 5% were GI division directors. Most of the respondents
were in favor of the pilot program (85%). Only 63% of all respondents believed
that graduates of the pilot program would achieve the same level of competency in
GI as those who completed the traditional program. Overall, 71% believed
incorporation of the 3-year training model would increase interest and
participation in TH fellowships. CONCLUSIONS: Most of the academic GI and TH
division and fellowship program directors embrace competency-based fellowship
education and TH subspecialty training during the designated 3-year GI
fellowship. Future studies will be needed to reevaluate these beliefs after
several years.
PMID- 25111234
TI - Clinical and histologic features of azithromycin-induced liver injury.
AB - BACKGROUND & AIMS: Rare cases of azithromycin-induced hepatotoxicity have been
reported, with variable clinical and histologic features. We characterized
clinical features and outcomes of azithromycin-induced liver injury. METHODS: We
identified patients with azithromycin-induced liver injury from the Drug-Induced
Liver Injury Network Prospective Study who had causality scores of definite,
highly likely, or probable. Demographic, clinical, and laboratory data and 6
month outcomes were examined. RESULTS: Eighteen patients (72% female; mean age,
37 y) had causality scores of definite (n = 1), highly likely (n = 9), or
probable (n = 8). Common presenting symptoms were jaundice, abdominal pain,
nausea, and/or pruritus. For 16 patients, abnormal results from liver tests were
first detected 14 days after azithromycin cessation (range, 9-20 d). The median
duration of azithromycin treatment was 4 days (range, 2-7 d). The pattern of
injury was hepatocellular in 10 patients, cholestatic in 6 patients, and mixed in
2 patients. The mean peak level of alanine aminotransferase was 2127 IU/L, of
alkaline phosphatase was 481 IU/L, and of total bilirubin was 9.2 mg/dL. Liver
histology showed ductopenia and veno-occlusive changes in a few patients. Two
individuals had severe hypersensitivity cutaneous reactions. After 6 months, 8
patients had recovered, 4 patients had chronic injury, 1 patient died, and 1
patient underwent liver transplantation (outcomes were unavailable for 4
patients). Two of the patients who died or underwent liver transplantation had
underlying chronic liver disease. CONCLUSIONS: Azithromycin-induced liver injury
occurs within 1 to 3 weeks after azithromycin initiation and predominantly is
hepatocellular in nature. Although most patients recover fully, severe cutaneous
reactions, chronic injury, and serious complications leading to death or liver
transplantation can occur (ClinicalTrials.gov identifier, NCT00345930).
PMID- 25111237
TI - Electrochemical quantification of the antioxidant capacity of medicinal plants
using biosensors.
AB - The working area of a screen-printed electrode, SPE, was modified with the enzyme
tyrosinase (Tyr) using different immobilization methods, namely entrapment with
water-soluble polyvinyl alcohol (PVA), cross-linking using glutaraldehyde (GA),
and cross-linking using GA and human serum albumin (HSA); the resulting
electrodes were termed SPE/Tyr/PVA, SPE/Tyr/GA and SPE/Tyr/HSA/GA, respectively.
These biosensors were characterized by means of amperometry and EIS techniques.
From amperometric evaluations, the apparent Michaelis-Menten constant, Km', of
each biosensor was evaluated while the respective charge transfer resistance,
Rct, was assessed from impedance measurements. It was found that the SPE/Tyr/GA
had the smallest Km' (57 +/- 7) uM and Rct values. This electrode also displayed
both the lowest detection and quantification limits for catechol quantification.
Using the SPE/Tyr/GA, the Trolox Equivalent Antioxidant Capacity (TEAC) was
determined from infusions prepared with "mirto" (Salvia microphylla), "hHierba
dulce" (Lippia dulcis) and "salve real" (Lippia alba), medicinal plants commonly
used in Mexico.
PMID- 25111238
TI - An adaptive jitter mechanism for reactive route discovery in sensor networks.
AB - This paper analyses the impact of jitter when applied to route discovery in
reactive (on-demand) routing protocols. In multi-hop non-synchronized wireless
networks, jitter--a small, random variation in the timing of message emission--is
commonly employed, as a means to avoid collisions of simultaneous transmissions
by adjacent routers over the same channel. In a reactive routing protocol for
sensor and ad hoc networks, jitter is recommended during the route discovery
process, specifically, during the network-wide flooding of route request
messages, in order to avoid collisions. Commonly, a simple uniform jitter is
recommended. Alas, this is not without drawbacks: when applying uniform jitter to
the route discovery process, an effect called delay inversion is observed. This
paper, first, studies and quantifies this delay inversion effect. Second, this
paper proposes an adaptive jitter mechanism, designed to alleviate the delay
inversion effect and thereby to reduce the route discovery overhead and
(ultimately) allow the routing protocol to find more optimal paths, as compared
to uniform jitter. This paper presents both analytical and simulation studies,
showing that the proposed adaptive jitter can effectively decrease the cost of
route discovery and increase the path quality.
PMID- 25111236
TI - Liver involvement in early autosomal-dominant polycystic kidney disease.
AB - BACKGROUND & AIMS: Polycystic liver disease (PLD), the most common extrarenal
manifestation of autosomal-dominant polycystic kidney disease (ADPKD), has become
more prevalent as a result of increased life expectancy, improved renal survival,
reduced cardiovascular mortality, and renal replacement therapy. No studies have
fully characterized PLD in large cohorts. We investigated whether liver and cyst
volumes are associated with volume of the hepatic parenchyma, results from liver
laboratory tests, and patient-reported outcomes. METHODS: We performed a cross
sectional analysis of baseline liver volumes, measured by magnetic resonance
imaging, and their association with demographics, results from liver laboratory
and other tests, and quality of life. The data were collected from a randomized,
placebo-controlled trial underway at 7 tertiary-care medical centers to determine
whether the combination of an angiotensin I-converting enzyme inhibitor and
angiotensin II-receptor blocker was superior to the inhibitor alone, and whether
low blood pressure (<110/75 mm Hg) was superior to standard blood pressure (120
130/70-80 mm Hg), in delaying renal cystic progression in 558 patients with
ADPKD, stages 1 and 2 chronic kidney disease, and hypertension (age, 15-49 y).
RESULTS: We found hepatomegaly to be common among patients with ADPKD. Cysts and
parenchyma contributed to hepatomegaly. Cysts were more common and liver and cyst
volumes were greater in women, increasing with age. Patients with advanced
disease had a relative loss of liver parenchyma. We observed small abnormalities
in results from liver laboratory tests, and that splenomegaly and hypersplenism
were associated with PLD severity. Higher liver volumes were associated with a
lower quality of life. CONCLUSIONS: Hepatomegaly is common even in early stage
ADPKD and is not accounted for by cysts alone. Parenchymal volumes were larger,
compared with liver volumes of patients without ADPKD or with those predicted by
standardized equations, even among patients without cysts. The severity of PLD
was associated with altered biochemical and hematologic features, as well as
quality of life. ClinicalTrials.gov identifier: NCT00283686.
PMID- 25111239
TI - Colorimetric detection of Ehrlichia canis via nucleic acid hybridization in gold
nano-colloids.
AB - Canine monocytic ehrlichiosis (CME) is a major thick-bone disease of dog caused
by Ehrlichia canis. Detection of this causal agent outside the laboratory using
conventional methods is not effective enough. Thus an assay for E. canis
detection based on the p30 outer membrane protein gene was developed. It was
based on the p30 gene amplification using loop-mediated isothermal DNA
amplification (LAMP). The primer set specific to six areas within the target gene
were designed and tested for their sensitivity and specificity. Detection of DNA
signals was based on modulation of gold nanoparticles' surface properties and
performing DNA/DNA hybridization using an oligonucleotide probe. Presence of
target DNA affected the gold colloid nanoparticles in terms of particle
aggregation with a plasmonic color change of the gold colloids from ruby red to
purple, visible by the naked eye. All the assay steps were completed within 90
min including DNA extraction without relying on standard laboratory facilities.
This method was very specific to target bacteria. Its sensitivity with probe
hybridization was sufficient to detect 50 copies of target DNA. This method
should provide an alternative choice for point of care control and management of
the disease.
PMID- 25111240
TI - Genotyping single nucleotide polymorphisms using different molecular beacon
multiplexed within a suspended core optical fiber.
AB - We report a novel approach to genotyping single nucleotide polymorphisms (SNPs)
using molecular beacons in conjunction with a suspended core optical fiber (SCF).
Target DNA sequences corresponding to the wild- or mutant-type have been
accurately recognized by immobilizing two different molecular beacons on the core
of a SCF. The two molecular beacons differ by one base in the loop-probe and
utilize different fluorescent indicators. Single-color fluorescence enhancement
was obtained when the immobilized SCFs were filled with a solution containing
either wild-type or mutant-type sequence (homozygous sample), while filling the
immobilized SCF with solution containing both wild- and mutant-type sequences
resulted in dual-color fluorescence enhancement, indicating a heterozygous
sample. The genotyping was realized amplification-free and with ultra low-volume
for the required DNA solution (nano-liter). This is, to our knowledge, the first
genotyping device based on the combination of optical fiber and molecular
beacons.
PMID- 25111241
TI - Resource optimization scheme for multimedia-enabled wireless mesh networks.
AB - Wireless mesh networking is a promising technology that can support numerous
multimedia applications. Multimedia applications have stringent quality of
service (QoS) requirements, i.e., bandwidth, delay, jitter, and packet loss
ratio. Enabling such QoS-demanding applications over wireless mesh networks
(WMNs) require QoS provisioning routing protocols that lead to the network
resource underutilization problem. Moreover, random topology deployment leads to
have some unused network resources. Therefore, resource optimization is one of
the most critical design issues in multi-hop, multi-radio WMNs enabled with
multimedia applications. Resource optimization has been studied extensively in
the literature for wireless Ad Hoc and sensor networks, but existing studies have
not considered resource underutilization issues caused by QoS provisioning
routing and random topology deployment. Finding a QoS-provisioned path in
wireless mesh networks is an NP complete problem. In this paper, we propose a
novel Integer Linear Programming (ILP) optimization model to reconstruct the
optimal connected mesh backbone topology with a minimum number of links and relay
nodes which satisfies the given end-to-end QoS demands for multimedia traffic and
identification of extra resources, while maintaining redundancy. We further
propose a polynomial time heuristic algorithm called Link and Node Removal
Considering Residual Capacity and Traffic Demands (LNR-RCTD). Simulation studies
prove that our heuristic algorithm provides near-optimal results and saves about
20% of resources from being wasted by QoS provisioning routing and random
topology deployment.
PMID- 25111242
TI - High temperature, high power piezoelectric composite transducers.
AB - Piezoelectric composites are a class of functional materials consisting of
piezoelectric active materials and non-piezoelectric passive polymers,
mechanically attached together to form different connectivities. These composites
have several advantages compared to conventional piezoelectric ceramics and
polymers, including improved electromechanical properties, mechanical flexibility
and the ability to tailor properties by using several different connectivity
patterns. These advantages have led to the improvement of overall transducer
performance, such as transducer sensitivity and bandwidth, resulting in rapid
implementation of piezoelectric composites in medical imaging ultrasounds and
other acoustic transducers. Recently, new piezoelectric composite transducers
have been developed with optimized composite components that have improved
thermal stability and mechanical quality factors, making them promising
candidates for high temperature, high power transducer applications, such as
therapeutic ultrasound, high power ultrasonic wirebonding, high temperature non
destructive testing, and downhole energy harvesting. This paper will present
recent developments of piezoelectric composite technology for high temperature
and high power applications. The concerns and limitations of using piezoelectric
composites will also be discussed, and the expected future research directions
will be outlined.
PMID- 25111244
TI - Improved ionization energies for the two isomers of phenylpropargyl radical.
AB - The ionization of two resonantly stabilized radicals, namely 1-phenylpropargyl
(1PPR) and 3-phenylpropargyl (3PPR) are reinvestigated applying vacuum
ultraviolet synchrotron radiation and threshold photoelectron spectroscopy.
Ionization energies of 7.24+/-0.02 and 7.25+/-0.01 eV are obtained for 1 and 3PPR
respectively, which compare well with ab initio calculations. The quality of the
spectra are significantly improved mostly due to the application of a new high
photon-flux grating available at the VUV-beamline of Swiss Light Source. Resolved
vibrational features are assigned according to a Franck-Condon approach.
PMID- 25111243
TI - 3beta-Acetyl tormentic acid reverts MRP1/ABCC1 mediated cancer resistance through
modulation of intracellular levels of GSH and inhibition of GST activity.
AB - ABC transporter overexpression is an important mechanism of multidrug resistance
(MDR) and one of the main obstacles to successful cancer treatment. As these
proteins actively remove chemotherapeutics from the tumor cells, the
pharmacological inhibition of their activity is a possible strategy to revert
drug resistance. Moreover, the ability of MDR inhibitors to sensitize resistant
cells to conventional drugs is important for their clinical use. Evidence has
shown that the multidrug resistance protein 1 (MRP1/ABCC1) is a negative
prognostic marker in patients with lung, gastric, or breast cancers or
neuroblastoma. Previous data have shown that 3beta-acetyl tormentic acid (3ATA)
inhibits the transport activity of the protein MRP1/ABCC1. In this study, we
evaluated the ability of 3ATA to sensitize an MDR cell line (GLC4/ADR), which
overexpresses MRP1, and investigated the anti-MRP1 mechanisms activated by 3ATA.
The results showed that 3ATA is able to reverse the resistance of the MDR cell
line to doxorubicin and vincristine, two drugs that are commonly used in cancer
chemotherapy. Regarding the sensitizing mechanism induced by 3ATA, this work
shows that the triterpene does not modulate the expression of MRP1/ABCC1 but is
able to reduce total intracellular glutathione (GSH) levels and decrease the
activity of glutathione-s-transferase (GST), the enzyme responsible for the
glutathione conjugation of xenobiotics. Together, these results show that 3ATA
sensitizes the MDR cell line overexpressing MRP1/ABCC1 to antineoplastic drugs
and that this effect is mediated by the modulation of intracellular levels of GSH
and GST activity.
PMID- 25111245
TI - A barium based coordination polymer for the activity assay of deoxyribonuclease
I.
AB - A new coordination polymer which shows an unusual 2D inorganic connectivity was
constructed. This compound exhibits distinct fluorescence quenching ability to
the dye-labeled single-stranded DNA probes with different lengths, based on which
an analytical method was developed for the activity assay of deoxyribonuclease I.
PMID- 25111246
TI - Highly-efficient synthesis of covalent porphyrinic cages via DABCO-templated
imine condensation reactions.
AB - We report a new approach to construct covalent porphyrinic cages with different
spacer lengths, in which the cage compounds have been conveniently synthesized in
quantitative yields, via DABCO-templated imine condensation reactions.
PMID- 25111247
TI - The effect of therapeutic hypothermia after cardiopulmonary resuscitation on ICAM
1 and NSE levels in sudden cardiac arrest rabbits.
AB - PURPOSE: To assess the effects of hypothermia and normothermia treatments for
sudden cardiac arrest (SCA) on brain injury recovery in rabbit models. METHODS:
Cardiopulmonary resuscitation (CPR) was implemented on apnea-induced SCA rabbit
models. Fifty survived rabbits were then randomly received hypothermia (n = 25,
32-34 degrees C) or normothermia treatment (n = 25, 39-39.5 degrees C) for 12
hours. The expected body temperatures were achieved within the first two hours,
maintained for ten hours and then rewarmed. The physiological parameters,
neurologic function, and the levels of adhesion molecule ICAM-1 and neuron
specific enolase (NSE) were monitored. RESULTS: Hypothermia-treated rabbits had
lower heart rate when achieving hypothermia (p < 0.0001) and higher SjvO2 after
hypothermia maintenance (p = 0.038). The hypothermia group achieved better brain
recovery performance according to the neurological deficit grading scale. ICAM-1
and NSE levels in both serum and CSF of the hypothermia group were lower than the
normothemia group (all p < 0.0001) during hypothermia maintenance. CONCLUSION:
Hypothermia treatment after CPR provides better outcome than normothermia
treatment in SCA rabbits. Hypothermia can reduce the ICAM-1 and NSE levels in
both serum and cerebrospinal fluid (CSF). This study supports the clinical
implementation of hypothermia treatment for SCA and reveals that ICAM-1 and NSE
are involved in the recovery of brain function after resuscitation.
PMID- 25111248
TI - How "situational" is judgment in situational judgment tests?
AB - Whereas situational judgment tests (SJTs) have traditionally been conceptualized
as low-fidelity simulations with an emphasis on contextualized situation
descriptions and context-dependent knowledge, a recent perspective views SJTs as
measures of more general domain (context-independent) knowledge. In the current
research, we contrasted these 2 perspectives in 3 studies by removing the
situation descriptions (i.e., item stems) from SJTs. Across studies, the
traditional contextualized SJT perspective was not supported for between 43% and
71% of the items because it did not make a significant difference whether the
situation description was included or not for these items. These results were
replicated across construct domains, samples, and response instructions. However,
there was initial evidence that judgment in SJTs was more situational when (a)
items measured job knowledge and skills and (b) response options denoted context
specific rules of action. Verbal protocol analyses confirmed that high scorers on
SJTs without situation descriptions relied upon general rules about the
effectiveness of the responses. Implications for SJT theory, research, and design
are discussed.
PMID- 25111249
TI - Modeling time-lagged reciprocal psychological empowerment-performance
relationships.
AB - Employee psychological empowerment is widely accepted as a means for
organizations to compete in increasingly dynamic environments. Previous empirical
research and meta-analyses have demonstrated that employee psychological
empowerment is positively related to several attitudinal and behavioral outcomes
including job performance. While this research positions psychological
empowerment as an antecedent influencing such outcomes, a close examination of
the literature reveals that this relationship is primarily based on cross
sectional research. Notably, evidence supporting the presumed benefits of
empowerment has failed to account for potential reciprocal relationships and
endogeneity effects. Accordingly, using a multiwave, time-lagged design, we model
reciprocal relationships between psychological empowerment and job performance
using a sample of 441 nurses from 5 hospitals. Incorporating temporal effects in
a staggered research design and using structural equation modeling techniques,
our findings provide support for the conventional positive correlation between
empowerment and subsequent performance. Moreover, accounting for the temporal
stability of variables over time, we found support for empowerment levels as
positive influences on subsequent changes in performance. Finally, we also found
support for the reciprocal relationship, as performance levels were shown to
relate positively to changes in empowerment over time. Theoretical and practical
implications of the reciprocal psychological empowerment-performance
relationships are discussed. (PsycINFO Database Record (c) 2014 APA, all rights
reserved).
PMID- 25111250
TI - The contextualized self: how team-member exchange leads to coworker
identification and helping OCB.
AB - This article develops the argument that team-member exchange (TMX) relationships
operate at both between- and within-group levels of analysis to influence an
employee's sense of identification with coworkers in the group and their helping
organizational citizenship behavior (OCB) directed at coworkers. Specifically, we
propose that relatively higher quality TMX relationships of an employee as
compared with other members of the group influence an employee's sense of
positive uniqueness, whereas higher average level of TMX quality in the group
creates a greater sense of belonging. Multilevel modeling analysis of field data
from 236 bank managers and their subordinates supports the hypotheses and
demonstrates 3 key findings. First, team members identify more with their
coworkers when they have high relative TMX quality compared with other group
members and are also embedded in groups with higher average TMX. Second,
identification with coworkers is positively related to helping OCB directed
toward team members. Finally, identification with coworkers mediates the
interactive effect of relative TMX quality and group average TMX quality on
helping. When TMX group relations allow individuals to feel a valued part of the
group, but still unique, they engage in higher levels of helping. Overall
moderated mediation analysis demonstrates that the mediated relationship linking
relative TMX quality with helping OCB via identification with coworkers is
stronger when group average TMX is high, but not present when group average TMX
is low. We discuss theoretical and practical implications and recommend future
research on multilevel conceptualizations of TMX.
PMID- 25111251
TI - Beyond the individual victim: multilevel consequences of abusive supervision in
teams.
AB - We conceptualize a multilevel framework that examines the manifestation of
abusive supervision in team settings and its implications for the team and
individual members. Drawing on Hackman's (1992) typology of ambient and
discretionary team stimuli, our model features team-level abusive supervision
(the average level of abuse reported by team members) and individual-level
abusive supervision as simultaneous and interacting forces. We further draw on
team-relevant theories of social influence to delineate two proximal outcomes of
abuse-members' organization-based self-esteem (OBSE) at the individual level and
relationship conflict at the team level-that channel the independent and
interactive effects of individual- and team-level abuse onto team members' voice,
team-role performance, and turnover intentions. Results from a field study and a
scenario study provided support for these multilevel pathways. We conclude that
abusive supervision in team settings holds toxic consequences for the team and
individual, and offer practical implications as well as suggestions for future
research on abusive supervision as a multilevel phenomenon. (PsycINFO Database
Record (c) 2014 APA, all rights reserved).
PMID- 25111252
TI - "Well, I'm tired of tryin'!" Organizational citizenship behavior and citizenship
fatigue.
AB - This study seeks to identify workplace conditions that influence the degree to
which employees feel worn out, tired, or on edge attributed to engaging in
organizational citizenship behavior (OCB) and also how this phenomenon, which we
refer to as citizenship fatigue, is associated with future occurrences of OCB.
Using data collected from 273 employees and their peers at multiple points in
time, we found that the relationship between OCB and citizenship fatigue depends
on levels of perceived organizational support, quality of team-member exchange
relationships, and pressure to engage in OCB. Specifically, the relationship
between OCB and citizenship fatigue is significantly stronger and positive when
perceived organizational support is low, and it is significantly stronger and
negative when the quality of team-member exchange is high and pressure to engage
in OCB is low. Our results also indicate that citizenship fatigue is negatively
related to subsequent acts of OCB. Finally, supplemental analyses reveal that the
relationship between OCB and citizenship fatigue may vary as a function of the
specific facet of OCB. We conclude with a discussion of the key theoretical and
practical implications of our findings.
PMID- 25111253
TI - Electronic control of ligand-binding preference of a myoglobin mutant.
AB - The L29F mutant of sperm whale myoglobin (Mb), where the leucine 29 residue was
replaced by phenylalanine (Phe), was shown to exhibit remarkably high affinity to
oxygen (O2), possibly due to stabilization of the heme Fe atom-bound O2 in the
mutant protein through a proposed unique electrostatic interaction with the
introduced Phe29, in addition to well-known hydrogen bonding with His64 [Carver,
T. E.; Brantley, R. E.; Singleton, E. W.; Arduini, R. M.; Quillin, M. L.;
Phillips, G. N., Jr.; Olson, J. S. J. Biol. Chem., 1992, 267, 14443-14450]. We
analyzed the O2 and carbon monoxide (CO) binding properties of the L29F mutant
protein reconstituted with chemically modified heme cofactors possessing a heme
Fe atom with various electron densities, to determine the effect of a change in
the electron density of the heme Fe atom (rho(Fe)) on the O2 versus CO
discrimination. The study demonstrated that the preferential binding of O2 over
CO by the protein was achieved through increasing rho(Fe), and the ordinary
ligand-binding preference, that is, the preferential binding of CO over O2, by
the protein was achieved through decreasing rho(Fe). Thus, the O2 and CO binding
preferences of the L29F mutant protein could be controlled through electronic
modulation of intrinsic heme Fe reactivity through a change in rho(Fe). The
present study highlighted the significance of the tuning of the intrinsic heme Fe
reactivity through the heme electronic structure in functional regulation of Mb.
PMID- 25111254
TI - Solvent-assisted lipid bilayer formation on silicon dioxide and gold.
AB - Planar lipid bilayers on solid supports mimic the fundamental structure of
biological membranes and can be investigated using a wide range of surface
sensitive techniques. Despite these advantages, planar bilayer fabrication is
challenging, and there are no simple universal methods to form such bilayers on
diverse material substrates. One of the novel methods recently proposed and
proven to form a planar bilayer on silicon dioxide involves lipid deposition in
organic solvent and solvent exchange to influence the phase of adsorbed lipids.
To scrutinize the specifics of this solvent-assisted lipid bilayer (SALB)
formation method and clarify the limits of its applicability, we have developed a
simplified, continuous solvent-exchange version to form planar bilayers on
silicon dioxide, gold, and alkanethiol-coated gold (in the latter case, a lipid
monolayer is formed to yield a hybrid bilayer) and varied the type of organic
solvent and rate of solvent exchange. By tracking the SALB formation process with
simultaneous quartz crystal microbalance-dissipation (QCM-D) and ellipsometry, it
was determined that the acoustic, optical, and hydration masses along with the
acoustic and optical thicknesses, measured at the end of the process, are
comparable to those observed by employing conventional fabrication methods (e.g.,
vesicle fusion). As shown by QCM-D measurements, the obtained planar bilayers are
highly resistant to protein adsorption, and several, but not all, water-miscible
organic solvents could be successfully used in the SALB procedure, with
isopropanol yielding particularly high-quality bilayers. In addition,
fluorescence recovery after photobleaching (FRAP) measurements demonstrated that
the coefficient of lateral lipid diffusion in the fabricated bilayers corresponds
to that measured earlier in the planar bilayers formed by vesicle fusion. With
increasing rate of solvent exchange, it was also observed that the bilayer became
incomplete and a phenomenological model was developed in order to explain this
feature. The results obtained allowed us to clarify and discriminate likely steps
of the SALB formation process as well as determine the corresponding influence of
organic solvent type and flow conditions on these steps. Taken together, the
findings demonstrate that the SALB formation method can be adapted to a
continuous solvent-exchange procedure that is technically minimal, quick, and
efficient to form planar bilayers on solid supports.
PMID- 25111255
TI - Immunomodulatory agents for the treatment of cachexia.
AB - PURPOSE OF REVIEW: In patients with advanced cancer, AIDS and end-stage organ
diseases, symptoms of cachexia syndrome include decrease in appetite, weight
loss, decreased performance status, and an increase in the systemic inflammatory
response. Inflammatory cytokines and other immune interactions affect the lean
tissue mass and body fat. It is hopeful that modulation of these inflammatory
interactions may contribute to the delay in the development and treatment of
cachexia. This review summarizes the current state of the art. RECENT FINDINGS:
This article covers the role of inflammatory response in cachexia, measurement of
inflammatory response, mechanism and measurement of cachexia, immunomodulation in
cancer, drugs targeting inflammatory cytokines, effect of exercise in cachexia,
and treatment of cancer cachexia using immunomodulatory agents. SUMMARY:
Understanding the immune response associated with cachexia may improve future
pharmacological modification of the cytokines. In addition, the multifactorial
contributions to the mechanisms of cachexia indicate that a multimodal approach
may be necessary to treat cachexia and its associated symptoms.
PMID- 25111256
TI - Chronobiology of chronic pain: focus on diurnal rhythmicity of neuropathic pain.
AB - PURPOSE OF REVIEW: Although circadian rhythmicity has long been recognized in
various nociceptive pain conditions such as arthritis, diurnal pain patterns in
neuropathic conditions have only recently been described. The purpose of this
article is to review emerging evidence and discuss future research to further
understand this phenomenon. RECENT FINDINGS: Secondary analyses of neuropathic
pain clinical trials demonstrate that pain intensity fluctuations exhibit a
distinct diurnal pattern that contrasts that of nociceptive pain conditions.
Ongoing preclinical investigations support the phenomenon of circadian pain
fluctuations and provide the opportunity to better describe pain chronobiology
and to elucidate underlying mechanisms of circadian pain rhythmicity. SUMMARY:
The observation of clinically relevant diurnal pain variability in neuropathic
conditions has important implications for future research and treatment of pain.
This is an immature research field, and further investigation is needed to better
characterize these patterns in more detail, investigate contributory mechanisms,
and to develop therapeutic strategies that exploit this phenomenon.
PMID- 25111257
TI - A behavioral study of healthy and cancer genes by modeling electrical network.
AB - In recent years, gene network modeling is gaining popularity in genomics to
monitor the activity profile of genes. More specifically, the objective of the
network modeling concept is to study the genetic behavior associated with
disease. Previous researchers have designed network model at nucleotide level
which produces more complexity for designing circuits mostly in case of gene
expression studies. Whereas the authors have designed the present network model,
based on amino acid level which is simpler as well as more appropriate for
prediction of the genetic abnormality. In the present concept, SISO continuous
and discrete system models of genes are realized using Foster network. The model
is designed based on hydropathy index value of amino acids to study the
biological system behavior. The time and phase response in continuous (s) domain
and pole-zero distribution in discrete (z) domain are used as measurement metric
in the present study. The simulated responses of the system show genetic
instability for cancer genes which truly reflects the medical reports. The
proposed modeling concept can be used, to accurately identify or separate out the
diseased genes from healthy genes.
PMID- 25111258
TI - Dihaloimidazolidinediones as versatile halodehydrating agents.
AB - Dihaloimidazolidinediones containing geminal dibromides, dichlorides, or
diiodides were synthesized and used to transform various alcohols to their
corresponding alkyl halides in high yields and under mild conditions. High
functional group tolerance and, in many cases, high selectivities were observed.
Efforts toward elucidating the mechanism revealed that significant charge build
up may occur at the eventual halogen containing carbon nucleus prior to
substitution.
PMID- 25111259
TI - A new class of organocatalysts: sulfenate anions.
AB - Sulfenate anions are known to act as highly reactive species in the organic
arena. Now they premiere as organocatalysts. Proof of concept is offered by the
sulfoxide/sulfenate-catalyzed (1-10 mol%) coupling of benzyl halides in the
presence of base to generate trans-stilbenes in good to excellent yields (up to
99%). Mechanistic studies support the intermediacy of sulfenate anions, and the
deprotonated sulfoxide was determined to be the resting state of the catalyst.
PMID- 25111266
TI - Computational studies support the role of the C7-sibirosamine sugar of the
pyrrolobenzodiazepine (PBD) sibiromycin in transcription factor inhibition.
AB - The pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are a group of sequence-selective,
DNA minor-groove binding agents that covalently attach to guanine residues.
Originally derived from Streptomyces species, a number of naturally occurring PBD
monomers exist with varying A-Ring and C2-substituents. One such agent,
sibiromycin, is unusual in having a glycosyl residue (sibirosamine) at its A-Ring
C7-position. It is the most cytotoxic member of the naturally occurring PBD
family and has the highest DNA-binding affinity. Recently, the analogue 9
deoxysibiromyin was produced biosynthetically by Yonemoto and co-workers.1
Differing only in the loss of the A-Ring C9-hydroxyl group, it was reported to
have a significantly higher DNA-binding affinity than sibiromycin based on DNA
thermal denaturation studies, although these data have since been retracted.2 As
deletion of the C9-OH moiety, which points toward the DNA minor groove floor,
might intuitively be expected to reduce DNA-binding affinity through the loss of
hydrogen bonding, we carried out molecular dynamics simulations on the
interaction of both molecules with DNA over a 10 ns time-course in explicit
solvent. Our results suggest that the two molecules may differ in their sequence
selectivity and that 9-deoxysibiromycin should have a lower binding affinity for
certain sequences of DNA compared to sibiromycin. Our molecular dynamics results
indicate that the C7-sibirosamine sugar does not form hydrogen bonding
interactions with groups in the DNA minor-groove wall as previously reported, but
instead points orthogonally out from the minor groove where it may inhibit the
approach of DNA control proteins such as transcription factors. This was
confirmed through a docking study involving sibiromycin and the GAL4
transcription factor, and these results could explain the significantly enhanced
cytotoxicity of sibiromycin compared to other PBD family members without bulky C7
substituents.
PMID- 25111267
TI - Chiral multidentate oxazoline ligands based on cyclophosphazene cores: synthesis,
characterization and complexation studies.
AB - Chiral oxazoline based bi and hexadentate ligands built on cyclophosphazene cores
have been synthesized and characterized. (NPPh2)2[NP(m-OC6H4C(O)OCH3)2] (1) was
prepared by the reaction of gem-(NPPh2)2(NPCl2) with methyl-3-hydroxy benzoate in
the presence of Cs2CO3. Compound 1 was converted to the dicarboxylic acid
(NPPh2)2[NP(m-OC6H4C(O)OH)2] (2) by base promoted hydrolysis with KO(t-Bu). The
dicarboxylic acid 2 on reaction with oxalyl chloride followed by (S)-(+)-2-amino
3-methyl-1-butanol, triethylamine and mesyl chloride was converted to the C2
symmetric phosphazene based chiral bisoxazoline ligand (NPPh2)2[NP{m-OC6H4(4-iPr
2-Ox)}2] (3) (Ox = oxazolinyl). A similar C2-symmetric bisoxazoline derivative
having an oxazoline group attached to the para position of the phenyl ring was
also synthesized starting from (NPPh2)2[NP(p-OC6H4C(O)OCH3)2] (4) which was first
converted to the dicarboxylic acid (NPPh2)2[NP(p-OC6H4C(O)OH)2] (5) and finally
to (NPPh2)2[NP{p-OC6H4(4-iPr-2-Ox)}2] (6) and (NPPh2)2[NP{p-OC6H4(4-Ph-2-Ox)}2]
(7) under similar reaction conditions. Reaction of 6 with Pd(OAc)2 in acetic acid
at room temperature and with PdCl2(C6H5CN)2 in refluxing benzene resulted in
chiral palladium complexes Pd(OAc)2(NPPh2)2[NP{p-OC6H4(4-iPr-2-Ox)}2] (8) and
PdCl2(NPPh2)2[NP{p-OC6H4(4-iPr-2-Ox)}2] (9), respectively. The utility of these
palladium complexes as chiral catalysts for the asymmetric rearrangement of
trichloroacetimidates to trichloroacetamides has been explored. The
hexa(methylbenzoate) derivative of cyclophosphazene [PN(OC6H4COOCH3)2]3 (10) on
treatment with KO(t-Bu) and H2O gave the hexacarboxylic acid derivative
[PN(OC6H4COOH)2]3 (11), which on treatment with oxalyl chloride followed by (S)
(+)-2-amino-3-methyl-1-butanol/(S)-(+)-2-phenylglycinol, triethylamine and mesyl
chloride was converted to the C3-symmetric cyclophosphazene based chiral
hexaoxazoline ligands [PN{OC6H4(4-iPr-2-Ox)}2]3 (12) and [PN{OC6H4(4-Ph-2-Ox)}2]3
(13). The bis(phebox) derivative of the cyclophosphazene was prepared starting
from (NPPh2)2[NP{OC6H3(COOCH3)2}2] (14), by the reaction of gem-Ph4P3N3Cl2 with
dimethyl 5-hydroxyisophthalate in the presence of Cs2CO3. Compound 14 was
converted to the tetracarboxylic acid (NPPh2)2[NP{OC6H3(COOH)2}2] (15) by base
promoted hydrolysis with KO(t-Bu). The tetracarboxylic acid 15 on reaction with
oxalyl chloride followed by (S)-(+)-2-amino-3-methyl-1-butanol/(S)-(+)-2
phenylglycinol, triethylamine and mesyl chloride was converted to the bis(phebox)
substituted tetraphenylcyclophosphazene derivatives (NPPh2)2[NP{OC6H3(4-iPr-2
Ox)2}2] (16)/(NPPh2)2[NP{OC6H3(4-Ph-2-Ox)2}2] (17). A similar tetra(phebox)
derivative was synthesized from (NPPh2)[NP{OC6H3(COOCH3)2}2]2 (18) which was
first converted to (NPPh2)[NP{OC6H3(COOH)2}2]2 (19) and further converted to the
tetra(phebox) derivative (NPPh2) [NP{OC6H3(4-Ph-2-Ox)2}2]2 (20). All new
compounds were characterized by IR, NMR [(1)H, (13)C{(1)H} and (31)P{(1)H}] and
HRMS studies. Compounds 1, 2, 4, 5, 7, 14 and 18 have also been structurally
characterized.
PMID- 25111268
TI - Optical properties of 4-bromobenzaldehyde derivatives in chloroform solution.
AB - In this work we give a deeper insight into the electronic structure of a series
of purely organic molecules that were recently employed as building blocks in
crystals with very efficient phosphorescent emission. With this purpose, the low
lying excited states of a series of 4-bromobenzaldehyde derivatives in chloroform
solution are explored by means of time-dependent density functional theory
(TDDFT) calculations, together with the absorption, fluorescence, and
phosphorescence experimental spectra. The optical properties of the studied
molecular models are extensively discussed, in terms of the frontier molecular
orbitals involved in the relevant electronic transitions, the recorded and
simulated absorption profiles, and the molecular geometries and transition
energies of the emitting states. The calculations eventually help in the
assignment of the character of the lowest lying singlet and triplet emitting
states for these compounds.
PMID- 25111269
TI - New media in pediatric surgery: innovations that have changed the way we educate
and communicate.
PMID- 25111270
TI - Comparative Analysis of Modified Laparoscopic Swenson and Laparoscopic Soave
Procedure for Short-Segment Hirschsprung Disease in Children.
AB - INTRODUCTION: This clinical analysis compared the characteristics and outcomes of
modified laparoscopic Swenson (MLSw) and laparoscopic Soave (LS) procedures for
short-segment Hirschsprung disease (HD) in children. PATIENTS AND METHODS: This
clinical analysis involved a retrospective series of 42 pediatric patients with
HD who underwent surgery from March 2007 to July 2012. Patients were divided into
two groups: the LS group (n = 15) and the MLSw group (n = 27). Preoperative,
operative, and postoperative data were collected, through patient follow-up
periods ranging from 12 to 48 months, to compare perioperative/operative
characteristics, postoperative complications, and outcomes between the two
groups. Major measurements were analyzed statistically. RESULTS: On average, the
patients in the LS group had a longer operating time (mean +/- standard
deviation, 199 +/- 60 minutes) than those in the MLSw group (148 +/- 23 minutes)
(p < 0.05). Blood loss was significantly less in the MLSw group (10 +/- 7 mL)
than in the LS group (26 +/- 14 mL) (p < 0.05). There was no difference in
feeding time between the two groups (p > 0.05). The MLSw group was discharged
after a shorter hospitalization time (8 +/- 2 days) than the LS group (12 +/- 4
days) (p < 0.05). The MLSw group had lower incidences of soiling (5, 18.5% vs. 7,
46.7%) and constipation (1, 3.7% vs. 3, 20%) than the LS group in the early
postoperative period, but no difference was found between the two groups in the
rate of complications during the late postoperative period. CONCLUSIONS: The MLSw
procedure did not increase the risk of injury to vital intrapelvic structures or
the incidence of complications in surgery for short-segment HD. The early
postoperative outcome was much better in the MLSw group than in the LS group, but
long-term outcomes were similar. However, the MLSw procedure was simpler,
resulting in reduced operating time and less intraoperative blood loss.
PMID- 25111271
TI - Highly Efficient Conservative Treatment of Pectus Carinatum in Compliant
Patients.
AB - PURPOSE: Pectus carinatum is a thoracic deformity, which causes severe
psychological problems for affected patients but almost no physical limitations.
Invasive procedures are difficult to justify for this reason. We present a
conservative therapy which leads to complete resolution in most cases when
performed properly. METHODS: Between January 2008 and December 2012, 69 patients
from 4 to 17 years with pectus carinatum were treated with a custom-fitted brace.
Patients were stratified in children, adolescents, and adults. RESULTS: Mean
therapy time was 7 months. Mean time of daily brace wearing was 12 to 15 hours.
The results were evaluated by pictures taken before and after the therapy and
from a patient interview. Standardized lateral views revealed a mean correction
angle of 10 degrees in the children's group and 5 degrees in the adolescent
group. In the adolescent group, 82% of patients judged the result as "excellent"
or "good." In this large group with 56 patients, those who reported the result
"unchanged" had a mean daily brace wearing time of 8.73 hours, those who judged
the result as "good" 14.53 hours, and those who judged the result as "excellent"
18.36 hours. CONCLUSION: Our results show that pectus carinatum is efficiently
treated with a customized brace therapy within 7 to 12 months. Best correction
can be achieved in children and young adolescents. Daily brace-wearing time
should be above 14 hours, ideally 24 hours. Duration of the treatment should be
around 1 year. Treatment results correlate directly with the cooperation of the
patients.
PMID- 25111272
TI - Maximizing lymph node retrieval during surgical resection of Wilms tumor.
AB - INTRODUCTION: Sampling lymph nodes (LNs) is independently associated with
decreased recurrence and improved survival for Wilms tumor (WT). Despite
sampling, we noted cases where a few or no LNs were identified after resection of
WT. We hypothesized fewer LNs were identified when submitted en bloc with the
tumor, compared with when submitted separately. PATIENTS/MATERIALS AND METHODS:
We conducted a retrospective chart review from 2003 to 2012 of WT resection
cases, examining the type of LN dissection, the specimens submitted to pathology,
number of LNs evaluated, and complications associated with the procedure.
RESULTS: We identified 74 children with WT; 59 of 74 (79.7%) had unilateral
disease and 15 of 74 (20.3%) had bilateral disease. With unilateral disease, more
LNs were identified by separate versus en bloc sampling (5.2 +/- 0.6 vs. 4.4 +/-
1.2 nodes, p=0.61). Both the methods identified fewer LNs compared with en
bloc+separate sampling (12.5 +/- 2.7 nodes, p<0.001 and p=0.04, respectively).
The majority of children with bilateral disease (10/15, 66.6%) did not have LN
sampling intraoperatively. When submitted separately, 83.3 +/- 3.8% of all LNs
were identified in the separate specimen, and two en bloc specimens that were
noted to have adenopathy intraoperatively had no LNs pathologically identified.
Few cases had complications, which did not appear associated with LN sampling.
CONCLUSIONS: En bloc+separate sampling yields the most LNs during resection of
WT. We recommend using this technique to facilitate the maximum number of LNs
evaluated in WT. Low rates of LN sampling in bilateral disease may indicate
decreased regard for sampling when tumor stage is already known.
PMID- 25111273
TI - Lysyl oxidase expression is decreased in the developing diaphragm and lungs of
nitrofen-induced congenital diaphragmatic hernia.
AB - INTRODUCTION: Malformation of the nonmuscular tissue components in congenital
diaphragmatic hernia (CDH) is thought to underlie the diaphragmatic defect,
causing intrathoracic herniation of abdominal viscera and thus disturbing normal
lung development. It has been shown that diaphragmatic and pulmonary
morphogeneses require the structural integrity of connective tissue, and
developmental mutations that inhibit the formation of extracellular matrix (ECM)
result in CDH with hypoplastic lungs. Lysyl oxidase (lox), an extracellular
enzyme that catalyzes the cross-linking of ECM proteins, plays an essential role
during diaphragmatic and pulmonary development by controlling the formation of
connective tissue. Furthermore, lox (-/-) knockouts exhibit abnormal connective
tissue with diaphragmatic defects and impaired airway morphogenesis. We designed
this study to investigate the hypothesis that diaphragmatic and pulmonary lox
expression is decreased in the nitrofen-induced CDH model. MATERIALS AND METHODS:
Timed-pregnant Sprague-Dawley rats were exposed to either nitrofen or vehicle on
gestational day 9 (D9), and fetuses were harvested on selected time points D15
and D18. The micro-dissected fetal diaphragms (n=48) and lungs (n=48) were
divided into two groups: control and nitrofen-exposed samples (n=12 per specimen
and time point, respectively). Diaphragmatic and pulmonary gene expression levels
of lox were analyzed by quantitative real-time polymerase chain reaction.
Immunohistochemical staining was performed to evaluate lox protein expression in
diaphragms and lungs. RESULTS: Relative mRNA expression of lox was significantly
reduced in diaphragms and lungs of nitrofen-exposed fetuses on D15 (0.29 +/- 0.08
vs. 0.12 +/- 0.05; p<0.05 and 0.52 +/- 0.44 vs. 0.20 +/- 0.04; p<0.05) and D18
(0.90 +/- 0.25 vs. 0.57 +/- 0.23; p<0.05 and 0.59 +/- 0.26 vs. 0.35 +/- 0.09;
p<0.05) compared with controls. Diaphragmatic and pulmonary immunoreactivity of
lox was markedly decreased in nitrofen-exposed fetuses on D15 and D18 compared
with controls. CONCLUSIONS: Decreased lox expression during diaphragmatic
development and lung branching morphogenesis may interfere with normal cross
linking of ECM proteins, disrupting the integrity of connective tissue, and
contributing to the diaphragmatic defect and impaired airway formation in the
nitrofen-induced CDH model.
PMID- 25111274
TI - Tumor-associated energy homeostasis: hepatoblastoma and neuroblastoma affect
glucose and lipid metabolism as well as ghrelin, GLP-1, and PYY in nude rats.
AB - INTRODUCTION: The "metabolic competition" for nutrients between cancer cells and
the patient has emerged as an important research area. For pediatric oncology, it
remains unclear whether the neuroendokrine regulation of appetite by
gastrointestinal hormones such as ghrelin "eat", GLP-1 (glucagon-like peptide,
"do not eat"), and PYY (peptide tyrosine-tyrosine, "do not eat") is influenced by
tumor growth. MATERIAL AND METHODS: In a prospective randomized study, human
hepatoblastoma (HB) and neuroblastoma (NB) cells (3 * 10(6)) were transplanted
into the abdominal wall of immune-incompetent (nu/nu) rats (ethic committee
approval: TVV43/11). Sham-operated animals received cell culture medium only.
Tumor growth was allowed for 8 weeks. Then, all the animals underwent a 2-hour
oGTT (oral glucose tolerance test) and were assessed for serum levels of glucose,
insulin, ghrelin, GLP-1, and PYY. Finally, all tumor masses and adipose tissues
were excised and calculated. RESULTS: Total body weight (including tumor masses)
differed for HB (329+31 g), but not for NB (358+22 g) compared with Sham (361+35
g). Subcutaneous adipose tissue was significantly decreased for both the tumor
groups (HB=2.6 g, NB=2.1 g, and Sham=3.5 g). Only for NB, fasting glucose (3.4 +
0.6 mmol/L) and insulin (0.89+0.11 ng/mL) levels were significantly decreased
compared with Sham (4.4+0.6 mmol/L; 1.19+0.36 ng/mL) only. During the oGTT (all
data calculated as area under the curve, AUC) glucose levels were significantly
increased for HB (104 +/- 10) and NB (102 +/- 13) compared with Sham (84 +/- 3),
but insulin levels remained similar for either group. Triglyceride levels were
increased for HB (0.51 mmol/L) and especially NB (0.73 mmol/L) compared with Sham
(0.34 mmol/L). Inflammatory parameters did not differ between the groups. Total
ghrelin levels were significantly increased for NB (111 +/- 10) and altered for
HB (102 +/- 15) compared with Sham (84 +/- 8). Vice versa GLP-1 was statistically
decreased in HB (92 +/- 7) and NB (88 +/- 12) compared with Sham (127 +/- 13).
Finally, PYY levels were nonsignificantly reduced for HB (117 +/- 5) and NB (120
+/- 4) compared with Sham (146 +/- 12).
PMID- 25111275
TI - Perioperative management after high-dose chemotherapy with autologous or
allogeneic hematopoietic stem cell transplantation for pediatric solid tumors.
AB - INTRODUCTION: An increasing number of children with advanced malignancies have
recently received high-dose chemotherapy (HDC) with hematopoietic stem cell
transplantation (HSCT), followed by surgery. In this study, we reviewed our
experience with surgery after HDC and autologous (auto) or allogeneic (allo) HSCT
to elucidate the problems associated with this treatment and establish the
optimum surgical management strategy. PATIENTS AND METHODS: We retrospectively
reviewed the cases of 24 children with advanced malignancy treated with HDC and
HSCT before tumor resection at our institution. The tumors included 18
neuroblastomas, 5 soft tissue sarcomas, 2 hepatoblastomas, and 1 Wilms tumor. The
source of hematopoietic stem cells was auto-HSCT in 19 patients and allo-HSCT in
5 patients. To be able to undergo surgery, it was necessary that the patient's
general condition, including hemostasis, should be fairly good and that the
results of hematological examinations should include a white blood cell (WBC)
count of>1,000/uL, hemoglobin level of>10 g/dL and platelet count of>5 *
10(4)/uL. RESULTS: The mean duration before WBC recovery after HSCT was 14.5 +/-
1.4 days after auto-HSCT and 23.8 +/- 1.2 days after allo-HSCT, respectively
(p<0.01). The mean duration before platelet recovery after HSCT was 46.5 +/- 5.2
days for auto-HSCT and 48.6 +/- 5.5 days for allo-HSCT (not significant [n.s.]).
The mean interval between allo-HSCT and surgery was significantly longer (92.8 +/
6.2 days) than that between auto-HSCT and surgery (57.0 +/- 3.9 days) (p<0.01),
likely because of the use of steroids and immunosuppressants after HSCT. The
tumors were completely resected in all cases without severe complications. All
the patients treated with allo-HSCT had an acute graft versus host (aGVH)
reaction at 2 to 3 weeks after HSCT, and specifically required the administration
of steroids and immunosuppressants to prevent aGVH. The postoperative
complications included paralytic ileus in two cases and a tacrolimus-associated
encephalopathy in one case involving allo-HSCT. In half of the patients, the WBC
count was not elevated after surgery, whereas the postoperative serum C-reactive
protein (CRP) level was elevated in all cases. CONCLUSIONS: Our data indicate
that surgical treatment can be safely performed even after HDC with HSCT if
attention is paid to myelosuppression and the adverse effects of both
chemotherapeutic agents and immunosuppressants.
PMID- 25111276
TI - Nursing Intervention for Outpatient Rehabilitation in Pediatric Patients with
Hirschsprung Disease after Colectomy.
AB - OBJECTIVE: The present study was designed to evaluate the effectiveness of a
nursing intervention program for outpatient rehabilitation of children with
Hirschsprung-associated enterocolitis (HAEC) after radical colectomy for
Hirschsprung disease (HD). BACKGROUND: Postoperative outcomes severely affect the
quality of life in pediatric HD patients after operation. The improvement in
defecation function is regarded as one of the most useful parameters to evaluate
the quality of life in HD patients after radical intestinal resection. A close
attention should also be paid to the patients' ability of social adaptation.
METHODS: This prospective, randomized control trial enrolled 85 pediatric
patients with HAEC after colectomy. They were randomly divided into the control
and intervention groups. All the patients were followed up for 6 to 12 months
after initial HAEC treatment. RESULTS: The intervention group had a lower
enterocolitis recurrence rate than the control group, with a better ability to
control defecation and their parents had better rehabilitation nursing knowledge
(p < 0.05). The degree of parents' satisfaction regarding the outcome was
significantly better in the intervention group than that in the control group (p
< 0.05). CONCLUSION: A systemic rehabilitation nursing program could decrease
enterocolitis recurrence, improve the recovery of anorectal functions, and
enhance the quality of life in the pediatric patients after radical colectomy.
PMID- 25111277
TI - What is "telemedicine" and what does it mean for a pediatric surgeon?
AB - Telemedicine is a broad term and has recently become a household term in the
medical field. However, there are many interpretations as to what the term
"telemedicine" means. There are many facets to telemedicine and here we describe
all of the elements of telemedicine, a glossary of terms, and how they relate to
pediatric surgery.
PMID- 25111278
TI - Telementoring: the surgical tool of the future.
AB - With decreased resident experience during training and the constant evolution of
new surgical techniques, surgeons are at risk for complications during the early
part of the learning curve. Mentorship by experienced surgeons may mitigate these
complications. The availability of such advanced telepresence technology makes it
logical that this will be used as part of the model to proctor, mentor, and train
practicing surgeons. Here, we review the current state of telementoring.
PMID- 25111279
TI - Online resources in pediatric surgery: the new era of medical information.
AB - Tele-education has the potential to facilitate rapid sharing and dissemination of
current research and knowledge among pediatric surgeons around the world.
Classically, the exchange of surgical research occurred via national surgical
conferences, articles published in peer-reviewed journals, and textbooks. The
advent of Web 2.0 and the rapid pace of technologic advancement have allowed
knowledge, education, and research to be exchanged online. Virtual symposiums act
as online conferences where participants present and debate new research and
surgical techniques in real-time web meetings. Resource libraries allow up-to
date information to be archived and viewed at the user's convenience, bypassing
the need to wait long periods for paper publications. Tele-education allows
pediatric surgeons to connect and share ideas around the world, while saving time
and money.
PMID- 25111280
TI - How pediatric surgeons use social media to attract new patients.
AB - Social media has changed the landscape of online interaction for all doctors
including pediatric surgeons. Of course the public including our patients and
potential new patients having immediate access to these sites through mobile
devices and iPads has contributed immensely to this phenomenon. Nonetheless, it
seems that we are all rushing to get in front of our target audience and to
engage in a relationship with them in a cost-effective fashion. This article will
discuss the role of the Internet and media and how you can use this technology to
attract new pediatric patients to your practice.
PMID- 25111282
TI - Delirium and hypovitaminosis D: neuroimaging findings.
AB - The authors examined the frequency of neuroimaging findings of cortical atrophy
and/or cerebrovascular disease in patients with delirium with hypovitaminosis D
and normal vitamin D levels. Of 32 patients with delirium with hypovitaminosis D
who were neuroimaged, 91.4% had neuroimaging findings, despite only five cases
having a comorbid diagnosis of dementia. Similar frequencies of cortical atrophy
and/or cerebrovascular disease were found in patients with delirium with normal
vitamin D levels. Further research with a larger sample size is needed to compare
neuroimaging findings between normal patients and patients with hypovitaminosis D
with delirium.
PMID- 25111281
TI - Osteoblast maturation on microtextured titanium involves paracrine regulation of
bone morphogenetic protein signaling.
AB - Osteoblasts are sensitive to surface microtopography and chemistry. Osteoblast
differentiation and maturation are higher in vitro and bone formation and
osseointegration enhanced in vivo on microstructured titanium (Ti) compared to
smooth surfaces. Cells increased BMP2 expression on microtextured Ti alloy,
suggesting a paracrine role in regulating osteoblast maturation. However, recent
studies show that exogenous BMP2 inhibits osteoblast production of anti
inflammatory cytokines and osteocalcin, indicating that control of BMP-signaling
may be involved. This study examined whether cells modulate BMP ligands,
receptors, and inhibitors during osteoblast maturation on Ti, specifically
focusing on the roles of BMP2 and Noggin (NOG). mRNA and protein for BMP2, BMP4,
and BMP7 and receptors BMPR1A, BMPR1B, and BMPR2, and BMP inhibitors were
upregulated on microtextured surfaces in comparison to smooth surfaces.
Maturation on microstructured Ti was slightly enhanced with exogenous BMP2 while
NOG addition inhibited osteoblast maturation. Cells with NOG knocked down
significantly increased osteoblast maturation. These results demonstrate that BMP
related molecules are controlled during osteoblast maturation on microstructured
Ti surfaces and that endogenous NOG is an important regulator of the process.
Modifying paracrine BMP signaling may yield more robust bone formation than
application of exogenous BMPs.
PMID- 25111284
TI - Editorial.
PMID- 25111283
TI - Hybrid elastin-like polypeptide-polyethylene glycol (ELP-PEG) hydrogels with
improved transparency and independent control of matrix mechanics and cell ligand
density.
AB - Hydrogels have been developed as extracellular matrix (ECM) mimics both for
therapeutic applications and basic biological studies. In particular, elastin
like polypeptide (ELP) hydrogels, which can be tuned to mimic several biochemical
and physical characteristics of native ECM, have been constructed to encapsulate
various types of cells to create in vitro mimics of in vivo tissues. However, ELP
hydrogels become opaque at body temperature because of ELP's lower critical
solution temperature behavior. This opacity obstructs light-based observation of
the morphology and behavior of encapsulated cells. In order to improve the
transparency of ELP hydrogels for better imaging, we have designed a hybrid ELP
polyethylene glycol (PEG) hydrogel system that rapidly cross-links with
tris(hydroxymethyl) phosphine (THP) in aqueous solution via Mannich-type
condensation. As expected, addition of the hydrophilic PEG component
significantly improves the light transmittance. Coherent anti-Stokes Raman
scattering (CARS) microscopy reveals that the hybrid ELP-PEG hydrogels have
smaller hydrophobic ELP aggregates at 37 degrees C. Importantly, this hydrogel
platform enables independent tuning of adhesion ligand density and matrix
stiffness, which is desirable for studies of cell-matrix interactions. Human
fibroblasts encapsulated in these hydrogels show high viability (>98%) after 7
days of culture. High-resolution confocal microscopy of encapsulated fibroblasts
reveals that the cells adopt a more spread morphology in response to higher RGD
ligand concentrations and softer gel mechanics.
PMID- 25111285
TI - Psychometric properties of the Geriatric Anxiety Inventory (GAI) and its short
form (GAI-SF) in a clinical and non-clinical sample of older adults.
AB - BACKGROUND: The Geriatric Anxiety Inventory is a 20-item geriatric-specific
measure of anxiety severity. While studies suggest good internal consistency and
convergent validity, divergent validity from measures of depression are weak.
Clinical cutoffs have been developed that vary across studies due to the small
clinical samples used. A six-item short form (GAI-SF) has been developed, and
while this scale is promising, the research assessing the psychometrics of this
scale is limited. METHODS: This study examined the psychometric properties of GAI
and GAI-SF in a large sample of 197 clinical geriatric participants with a
comorbid anxiety and unipolar mood disorder, and a non-clinical control sample (N
= 59). RESULTS: The internal consistency and convergent validity with other
measures of anxiety was adequate for GAI and GAI-SF. Divergent validity from
depressive symptoms was good in the clinical sample but weak in the total and non
clinical samples. Divergent validity from cognitive functioning was good in all
samples. The one-factor structure was replicated for both measures. Receiver
Operating Characteristic analyses indicated that the GAI is more accurate at
identifying clinical status than the GAI-SF, although the sensitivity and
specificity for the recommended cutoffs was adequate for both measures.
CONCLUSIONS: Both GAI and GAI-SF show good psychometric properties for
identifying geriatric anxiety. The GAI-SF may be a useful alternative screening
measure for identifying anxiety in older adults.
PMID- 25111286
TI - Prevalence of HPV and variation of HPV 16/HPV 18 E6/E7 genes in cervical cancer
in women in South West China.
AB - Genetic variations of High-Risk HPV E6/E7 may be associated with the development
of cervical cancer in specific geographic regions. Few data have been reported
about the HPV prevalence and E6/E7 variants among cervical cancer patients in
Southwest China. This study was designed to investigate the prevalence of HPV and
E6/E7 variants of most prevalent HPV among cervical cancer patients in Southwest
China. After genotyping, E6/E7 genes of most prevalent HR HPV samples were
sequenced and analyzed. Phylogenetic trees were then constructed, followed by an
analysis of the diversity of secondary structure and selection pressures. HPV 16
(73.8%) and HPV 18 (16.4%) are the most prevalent infection types among cervical
cancer patients, followed by HPV 58, HPV 56 and HPV 59, which is different from
the high HPV 58 infection rate of outpatients in this region. Eighteen single
nucleotide changes were observed in HPV 16 E6 with 13/18 non-synonymous mutations
(5 in beta sheet and 2 in alpha helix). Ten single nucleotide changes were
identified among HPV 16 E7 with 3/10 non-synonymous mutations. Three single
nucleotide changes were observed in HPV 18 E6 with one non-synonymous mutation,
and only one synonymous mutation was identified in HPV 18 E7. HPV 16 E6-D25E, E7
N29S and E7-T846C (S95S) exhibited a prevalent linkage mutation. The phylogenetic
tree demonstrates that European and Asian lineages were the main patterns. This
study may help understand the intrinsic geographical relatedness and oncogenic
potential of HR HPV and contributes further to research of diagnostic,
therapeutic and therapeutic vaccine strategy.
PMID- 25111289
TI - Global carbon benefits of material substitution in passenger cars until 2050 and
the impact on the steel and aluminum industries.
AB - Light-weighting of passenger cars using high-strength steel or aluminum is a
common emissions mitigation strategy. We provide a first estimate of the global
impact of light-weighting by material substitution on GHG emissions from
passenger cars and the steel and aluminum industries until 2050. We develop a
dynamic stock model of the global car fleet and combine it with a dynamic MFA of
the associated steel, aluminum, and energy supply industries. We propose four
scenarios for substitution of conventional steel with high-strength steel and
aluminum at different rates over the period 2010-2050. We show that light
weighting of passenger cars can become a "gigaton solution": Between 2010 and
2050, persistent light-weighting of passenger cars can, under optimal conditions,
lead to cumulative GHG emissions savings of 9-18 gigatons CO2-eq compared to
development business-as-usual. Annual savings can be up to 1 gigaton per year.
After 2030, enhanced material recycling can lead to further reductions: closed
loop metal recycling in the automotive sector may reduce cumulative emissions by
another 4-6 gigatons CO2-eq. The effectiveness of emissions mitigation by
material substitution significantly depends on how the recycling system evolves.
At present, policies focusing on tailpipe emissions and life cycle assessments of
individual cars do not consider this important effect.
PMID- 25111287
TI - Is there a role for base excision repair in estrogen/estrogen receptor-driven
breast cancers?
AB - Estrogen and estrogen metabolite-induced reactive oxygen species generation can
promote oxidative DNA base damage. If unrepaired, base damaging lesions could
accelerate mutagenesis, leading to a "mutator phenotype" characterized by
aggressive behavior in estrogen-estrogen receptor (ER)-driven breast cancer. To
test this hypothesis, we investigated 1406 ER(+) early-stage breast cancers with
20 years' long-term clinical follow-up data for DNA polymerase beta (pol beta),
flap endonuclease 1 (FEN1), AP endonuclease 1 (APE1), X-ray cross-complementation
group 1 protein (XRCC1), single-strand monofunctional uracil glycosylase-1
(SMUG1), poly (ADP-ribose) polymerase 1 (PARP1), ataxia telangiectasia mutated
and Rad3 related (ATR), ataxia telangiectasia mutated (ATM), DNA-dependent
protein kinase catalytic subunit (DNA-PKcs), Chk1, Chk2, p53, breast cancer
susceptibility gene 1 (BRCA1), and topoisomerase 2 (TOPO2) expression.
Multivariate Cox proportional hazards model was used to calculate a DNA repair
prognostic index and correlated to clinicopathological variables and survival
outcomes. Key base excision repair (BER) proteins, including XRCC1, APE1, SMUG1,
and FEN1, were independently associated with poor breast cancer-specific survival
(BCSS) (ps<=0.01). Multivariate Cox model stratified patients into four distinct
prognostic sub-groups with worsening BCSS (ps<0.01). In addition, compared with
prognostic sub-group 1, sub-groups 2, 3, and 4 manifest increasing tumor size,
grade, mitosis, pleomorphism, differentiation, lymphovascular invasion, high
Ki67, loss of Bcl-2, luminal B phenotype (ps<=0.01), and poor survival, including
in patients who received tamoxifen adjuvant therapy (p<0.00001). Our observation
supports the hypothesis that BER-directed stratification could inform appropriate
therapies in estrogen-ER-driven breast cancers. Antioxid.
PMID- 25111290
TI - Breaking down the reactivity of lambda(3)-iodanes: the impact of structure and
bonding on competing reaction mechanisms.
AB - The functionalization of arenes via diaryliodonium salts has gained considerable
attention in synthesis, as these compounds react under mild conditions.
Mechanistic studies have shown that the formation of corresponding lambda(3)
iodane intermediates takes a key role, as they determine the course and
selectivity of the reaction. Bridged diaryliodonium salts, featuring a
heterocyclic moiety involving the iodine atom, were shown to exhibit a distinctly
different reactivity, leading to different products. These products are not just
the result of reductive elimination reactions but may also arise via radical
mechanisms. Our quantum chemical calculations reveal that the lambda(3)-iodane
intermediate is also the "gateway" for reactions that are observed only for
strained bridged systems. At the same time, we find a remarkable affinity of the
hypervalent region to planarity for all reaction mechanisms. This also explains
the correlation between the size of the bridge connecting the aryl groups and the
reaction products observed. Furthermore, the energetics of these competing
reactions are examined by analysis of the mechanisms. Finally, using model
compounds, some of the basic features governing the reactivity of lambda(3)
iodanes are discussed.
PMID- 25111291
TI - Translational research in acute central nervous system injury: lessons learned
and the future.
AB - IMPORTANCE: Research to improve outcomes from acute central nervous system (CNS)
injury has progressed little, although limited examples (eg, induced hypothermia
for out-of-hospital ventricular fibrillation cardiac arrest and birth asphyxia
and tissue plasminogen activator for ischemic stroke) have proved that it is
possible to favorably alter outcome. OBJECTIVE: To chronicle the evolution of
preclinical research designed to provide therapeutic interventions for acute CNS
injury. EVIDENCE REVIEW: Preclinical literature cited by major clinical
intervention trials was systematically assessed with respect to fulfillment of
fundamental elements of experimental design in current guidelines. FINDINGS:
Preclinical studies of acute CNS injury to date have a poor record of adhering to
basic tenets of experimental design, including randomization, concealment of
treatment allocation, definition of sustained robustness of therapeutic benefit,
and emulation of clinical disease. Major clinical trials continue to be justified
and conducted on the basis of weak preclinical evidence. Publication of
preclinical research guidelines and endorsement by scientific journals have been
insufficient to alter practice. Novel approaches to preclinical therapeutic
development, including multicenter phase 3 trials and preclinical trial
registries that document a priori experimental design and primary dependent
variables, may overcome this intransigence and enhance possibility for
therapeutic breakthroughs. CONCLUSIONS AND RELEVANCE: Current knowledge of acute
CNS injury dictates that therapeutic discovery and translation apply known tenets
of sound experimental design and emulation of the clinical disorder targeted for
therapeutic intervention. Peer-review systems must demand these qualities in
proposed and published research to assess validity and potential for clinical
translation.
PMID- 25111292
TI - Mental health and substance use among bisexual youth and non-youth in Ontario,
Canada.
AB - Research has shown that bisexuals have poorer health outcomes than heterosexuals,
gays, or lesbians, particularly with regard to mental health and substance use.
However, research on bisexuals is often hampered by issues in defining
bisexuality, small sample sizes, and by the failure to address age differences
between bisexuals and other groups or age gradients in mental health. The Risk &
Resilience Survey of Bisexual Mental Health collected data on 405 bisexuals from
Ontario, Canada, using respondent-driven sampling, a network-based sampling
method for hidden populations. The weighted prevalence of severe depression (PHQ
9 >= 20) was 4.7%, possible anxiety disorder (OASIS >= 8) was 30.9%, possible
post-traumatic stress disorder (PCL-C >= 50) was 10.8%, and past year suicide
attempt was 1.9%. With respect to substance use, the weighted prevalence of
problem drinking (AUDIT >= 5) was 31.2%, and the weighted prevalence of illicit
polydrug use was 30.5%. Daily smoking was low in this sample, with a weighted
prevalence of 7.9%. Youth (aged 16-24) reported significantly higher weighted
mean scores on depression and post-traumatic stress disorder, and higher rates of
past year suicidal ideation (29.7% vs. 15.2%) compared with those aged 25 and
older. The burden of mental health and substance use among bisexuals in Ontario
is high relative to population-based studies of other sexual orientation groups.
Bisexual youth appear to be at risk for poor mental health. Additional research
is needed to understand if and how minority stress explains this burden.
PMID- 25111293
TI - Parental modelling of eating behaviours: observational validation of the Parental
Modelling of Eating Behaviours scale (PARM).
AB - Parents are important role models for their children's eating behaviours. This
study aimed to further validate the recently developed Parental Modelling of
Eating Behaviours Scale (PARM) by examining the relationships between maternal
self-reports on the PARM with the modelling practices exhibited by these mothers
during three family mealtime observations. Relationships between observed
maternal modelling and maternal reports of children's eating behaviours were also
explored. Seventeen mothers with children aged between 2 and 6 years were video
recorded at home on three separate occasions whilst eating a meal with their
child. Mothers also completed the PARM, the Children's Eating Behaviour
Questionnaire and provided demographic information about themselves and their
child. Findings provided validation for all three PARM subscales, which were
positively associated with their observed counterparts on the observational
coding scheme (PARM-O). The results also indicate that habituation to
observations did not change the feeding behaviours displayed by mothers. In
addition, observed maternal modelling was significantly related to children's
food responsiveness (i.e., their interest in and desire for foods), enjoyment of
food, and food fussiness. This study makes three important contributions to the
literature. It provides construct validation for the PARM measure and provides
further observational support for maternal modelling being related to lower
levels of food fussiness and higher levels of food enjoyment in their children.
These findings also suggest that maternal feeding behaviours remain consistent
across repeated observations of family mealtimes, providing validation for
previous research which has used single observations.
PMID- 25111294
TI - Alternatives to the six-minute walk test in pulmonary arterial hypertension.
AB - INTRODUCTION: The physiological response during the endurance shuttle walk test
(ESWT), the cycle endurance test (CET) and the incremental shuttle walk test
(ISWT) remains unknown in PAH. We tested the hypothesis that endurance tests
induce a near-maximal physiological demand comparable to incremental tests. We
also hypothesized that differences in respiratory response during exercise would
be related to the characteristics of the exercise tests. METHODS: Within two
weeks, twenty-one PAH patients (mean age: 54(15) years; mean pulmonary arterial
pressure: 42(12) mmHg) completed two cycling exercise tests (incremental
cardiopulmonary cycling exercise test (CPET) and CET) and three field tests
(ISWT, ESWT and six-minute walk test (6MWT)). Physiological parameters were
continuously monitored using the same portable telemetric device. RESULTS: Peak
oxygen consumption (VO(2peak)) was similar amongst the five exercise tests (p =
0.90 by ANOVA). Walking distance correlated markedly with the VO(2peak) reached
during field tests, especially when weight was taken into account. At 100%
exercise, most physiological parameters were similar between incremental and
endurance tests. However, the trends overtime differed. In the incremental tests,
slopes for these parameters rose steadily over the entire duration of the tests,
whereas in the endurance tests, slopes rose sharply from baseline to 25% of
maximum exercise at which point they appeared far less steep until test end.
Moreover, cycling exercise tests induced higher respiratory exchange ratio,
ventilatory demand and enhanced leg fatigue measured subjectively and
objectively. CONCLUSION: Endurance tests induce a maximal physiological demand in
PAH. Differences in peak respiratory response during exercise are related to the
modality (cycling vs. walking) rather than the progression (endurance vs.
incremental) of the exercise tests.
PMID- 25111295
TI - Biological construction of single-walled carbon nanotube electron transfer
pathways in dye-sensitized solar cells.
AB - We designed and mass-produced a versatile protein supramolecule that can be used
to manufacture a highly efficient dye-sensitized solar cell (DSSC). Twelve single
walled carbon-nanotube (SWNT)-binding and titanium-mineralizing peptides were
genetically integrated on a cage-shaped dodecamer protein (CDT1). A process
involving simple mixing of highly conductive SWNTs with CDT1 followed by TiO2
biomineralization produces a high surface-area/weight TiO2 -(anatase)-coated
intact SWNT nanocomposite under environmentally friendly conditions. A DSSC with
a TiO2 photoelectrode containing 0.2 wt % of the SWNT-TiO2 nanocomposite shows a
current density improvement by 80% and a doubling of the photoelectric conversion
efficiency. The SWNT-TiO2 nanocomposite transfers photon-generated electrons from
dye molecules adsorbed on the TiO2 to the anode electrode swiftly.
PMID- 25111297
TI - Novel method to characterize immune cells from human prostate tissue.
AB - BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common benign adenoma
and prostate cancer is the most frequent malignancy in men over 50 years of age
in the Western world, where it remains a significant health problem. Prostate
lesions are known to contain immune cells, which may contribute to the immune
control of tumor progression. However, due to their low numbers and restricted
access to necessary material it is difficult to isolate immune cells from
prostate tissue to characterize their immunological features. METHODS: An
efficient and robust method was developed to process prostate tissue and isolate
immune cells for phenotypic analysis by multicolor flow cytometry as downstream
application. Fresh prostate tissue from 11 patients undergoing surgery for
bladder outlet obstruction due to BPH was processed to evaluate the number,
viability, yield, and frequency of various immune cell types. RESULTS: The
presented method does not include enzymatic digestion nor incubation steps at 37
degrees C, increasing cellular viability and avoiding possible phenotypic
modification. Various immune cell populations were detected in all patient
samples and the median cellular viability was 90%. The number of detected events
of individual cell populations varied between patients. The median frequency of
different immune cell populations also varied, being 87% for the CD3- and 15% for
the CD3+ cell population. CONCLUSIONS: This novel method will allow the
phenotypic characterization of immune cell populations present in tumor tissue of
prostate cancer patients and promote development of novel approaches to
immunotherapy of the disease.
PMID- 25111296
TI - A new model for predicting non-sentinel lymph node status in Chinese sentinel
lymph node positive breast cancer patients.
AB - BACKGROUND: Our goal is to validate the Memorial Sloan-Kettering Cancer Center
(MSKCC) nomogram and Stanford Online Calculator (SOC) for predicting non-sentinel
lymph node (NSLN) metastasis in Chinese patients, and develop a new model for
better prediction of NSLN metastasis. METHODS: The MSKCC nomogram and SOC were
used to calculate the probability of NSLN metastasis in 120 breast cancer
patients. Univariate and multivariate analyses were performed to evaluate the
relationship between NSLN metastasis and clinicopathologic factors, using the
medical records of the first 80 breast cancer patients. A new model predicting
NSLN metastasis was developed from the 80 patients. RESULTS: The MSKCC and SOC
predicted NSLN metastasis in a series of 120 patients with an area under the
receiver operating characteristic curve (AUC) of 0.688 and 0.734, respectively.
For predicted probability cut-off points of 10%, the false-negative (FN) rates of
MSKCC and SOC were both 4.4%, and the negative predictive value (NPV) 75.0% and
90.0%, respectively. Tumor size, Kiss-1 expression in positive SLN and size of
SLN metastasis were independently associated with NSLN metastasis (p<0.05). A new
model (Peking University People's Hospital, PKUPH) was developed using these
three variables. The MSKCC, SOC and PKUPH predicted NSLN metastasis in the second
40 patients from the 120 patients with an AUC of 0.624, 0.679 and 0.795,
respectively. CONCLUSION: MSKCC nomogram and SOC did not perform as well as their
original researches in Chinese patients. As a new predictor, Kiss-1 expression in
positive SLN correlated independently with NSLN metastasis strongly. PKUPH model
achieved higher accuracy than MSKCC and SOC in predicting NSLN metastasis in
Chinese patients.
PMID- 25111298
TI - Impact of bottom trawling on deep-sea sediment properties along the flanks of a
submarine canyon.
AB - The offshore displacement of commercial bottom trawling has raised concerns about
the impact of this destructive fishing practice on the deep seafloor, which is in
general characterized by lower resilience than shallow water regions. This study
focuses on the flanks of La Fonera (or Palamos) submarine canyon in the
Northwestern Mediterranean, where an intensive bottom trawl fishery has been
active during several decades in the 400-800 m depth range. To explore the degree
of alteration of surface sediments (0-50 cm depth) caused by this industrial
activity, fishing grounds and control (untrawled) sites were sampled along the
canyon flanks with an interface multicorer. Sediment cores were analyzed to
obtain vertical profiles of sediment grain-size, dry bulk density, organic carbon
content and concentration of the radionuclide 210Pb. At control sites, surface
sediments presented sedimentological characteristics typical of slope
depositional systems, including a topmost unit of unconsolidated and bioturbated
material overlying sediments progressively compacted with depth, with
consistently high 210Pb inventories and exponential decaying profiles of 210Pb
concentrations. Sediment accumulation rates at these untrawled sites ranged from
0.3 to 1.0 cm y-1. Sediment properties at most trawled sites departed from
control sites and the sampled cores were characterized by denser sediments with
lower 210Pb surface concentrations and inventories that indicate widespread
erosion of recent sediments caused by trawling gears. Other alterations of the
physical sediment properties, including thorough mixing or grain-size sorting, as
well as organic carbon impoverishment, were also visible at trawled sites. This
work contributes to the growing realization of the capacity of bottom trawling to
alter the physical properties of surface sediments and affect the seafloor
integrity over large spatial scales of the deep-sea.
PMID- 25111299
TI - Biosynthetic pathway of the phytohormone auxin in insects and screening of its
inhibitors.
AB - Insect galls are abnormal plant tissues induced by galling insects. The galls are
used for food and habitation, and the phytohormone auxin, produced by the
insects, may be involved in their formation. We found that the silkworm, a non
galling insect, also produces an active form of auxin, indole-3-acetic acid
(IAA), by de novo synthesis from tryptophan (Trp). A detailed metabolic analysis
of IAA using IAA synthetic enzymes from silkworms indicated an IAA biosynthetic
pathway composed of a three-step conversion: Trp -> indole-3-acetaldoxime ->
indole-3-acetaldehyde (IAAld) -> IAA, of which the first step is limiting IAA
production. This pathway was shown to also operate in gall-inducing sawfly.
Screening of a chemical library identified two compounds that showed strong
inhibitory activities on the conversion step IAAld -> IAA. The inhibitors can be
efficiently used to demonstrate the importance of insect-synthesized auxin in
gall formation in the future.
PMID- 25111301
TI - The psychology of coordination and common knowledge.
AB - Research on human cooperation has concentrated on the puzzle of altruism, in
which 1 actor incurs a cost to benefit another, and the psychology of
reciprocity, which evolved to solve this problem. We examine the complementary
puzzle of mutualism, in which actors can benefit each other simultaneously, and
the psychology of coordination, which ensures such benefits. Coordination is
facilitated by common knowledge: the recursive belief state in which A knows X, B
knows X, A knows that B knows X, B knows that A knows X, ad infinitum. We test
whether people are sensitive to common knowledge when deciding whether to engage
in risky coordination. Participants decided between working alone for a certain
profit and working together for a potentially higher profit that they would
receive only if their partner made the same choice. Results showed that more
participants attempted risky coordination when they and their prospective partner
had common knowledge of the payoffs (broadcast over a loudspeaker) than when they
had only shared knowledge (conveyed to both by a messenger) or private knowledge
(revealed to each partner separately). These results support the hypothesis that
people represent common knowledge as a distinct cognitive category that licenses
them to coordinate with others for mutual gain. We discuss how this hypothesis
can provide a unified explanation for diverse phenomena in human social life,
including recursive mentalizing, performative speech acts, public protests,
hypocrisy, and self-conscious emotional expressions.
PMID- 25111300
TI - Mycobacterium Avium subsp. paratuberculosis isolates induce in vitro granuloma
formation and show successful survival phenotype, common anti-inflammatory and
antiapoptotic responses within ovine macrophages regardless of genotype or host
of origin.
AB - The analysis of the early macrophage responses, including bacterial growth within
macrophages, represents a powerful tool to characterize the virulence of clinical
isolates of Mycobcaterium avium susbp. paratuberculosis (Map). The present study
represents the first assessment of the intracellular behaviour in ovine monocyte
derived macrophages (MDMs) of Map isolates representing distinct genotypes (C, S
and B), and isolated from cattle, sheep, goat, fallow deer, deer, and wild boar.
Intracellular growth and survival of the selected isolates in ovine MDMs was
assessed by quantification of CFUs inside of the host cells at 2 h p.i. (day 0)
and 7 d p. i. using an automatic liquid culture system (Bactec MGIT 960).
Variations in bacterial counts over 7 days from the baseline were small, in a
range between 1.63 to 1.05-fold. After 7 d of infection, variations in the
estimated log10 CFUs between all the tested isolates were not statistically
significant. In addition, ovine MDMs exhibited enhanced anti-inflammatory,
antiapoptotic and antidestructive responses when infected with two ovine isolates
of distinct genotype (C and S) or with two C-type isolates from distinct hosts
(cattle and sheep); which correlated with the successful survival of these
isolates within ovine MDMs. A second objective was to study, based on an in vitro
granuloma model, latter stages of the infection by investigating the capacity of
two Map isolates from cattle and sheep to trigger formation of microgranulomas.
Upon 10 d p.i., both Map isolates were able to induce the formation of granulomas
comparable to the granulomas observed in clinical specimens with respect to the
cellular components involved. In summary, our results demonstrated that Map
isolates from cattle, sheep, goats, deer, fallow-deer and wild boar were able not
only to initiate but also to establish a successful infection in ovine
macrophages regardless of genotype.
PMID- 25111302
TI - Why side-effect outcomes do not affect intuitions about intentional actions:
properly shifting the focus from intentional outcomes back to intentional
actions.
AB - Over the last decade, many articles have suggested that the "badness" of side
effect outcomes influences perceivers' intuitions about intentionality,
contradicting the traditional notion that mental state inferences lead to moral
judgments rather than the reverse. Challenging this assertion, we argue that
typically, consideration of intentionality involves thinking about "intentional
actions" (things people do) rather than unintended outcomes. Across several
studies, we offer an explanatory framework describing why side-effect asymmetries
emerge. We first establish that people differentiate actions, outcomes, goals,
and side effects, associating intentions with goals but intentionality with
actions in furtherance of goals, and that each of these components is readily
identified in side-effect scenarios. We then demonstrate that when relationships
among actions, goals, and side effects are available for consideration in
response options, side-effect effects disappear. We additionally show that,
because actions are not explicitly referenced, people reinterpret questions about
the intentionality of side effects-particularly for harmful outcomes-as asking
about intentional actions that caused side effects, creating a mismatch between
participants' pragmatic and researchers' literal interpretations. Finally, we
demonstrate how harmful side effects shift perceivers' attention toward
considering agents' knowledge/awareness, whereas beneficial side effects focus
attention on intentions/motives, which serves a useful social purpose. We discuss
how perceptions of intentionality are not influenced by side-effect valence,
although, because of structural differences in how people view harm versus
benefit, outcomes influence which mental states perceivers consider important
when answering questions that are typically asked in side-effects research.
Beyond intentionality, we consider how these findings may shed light on trait
attribution processes, more generally.
PMID- 25111303
TI - Trusting others: the polarization effect of need for closure.
AB - Because trust-related issues inherently involve uncertainty, we expected
individuals' social-cognitive motivation to manage uncertainty--which is captured
by their need for closure--to influence their level of trust in others. Through
the results of 6 studies, we showed that higher need for closure was related to
more polarized trust judgments (i.e., low trust in distant others and high trust
in close others) in the case of both chronic and situational need for closure.
Moreover, participants with high need for closure did not revise their level of
trust when they received feedback about the trustees' actual trustworthiness,
whereas participants with low need for closure did. Overall, our findings
indicate that polarized (either high or low, as opposed to moderate) and
persistent levels of trust may serve people's seizing and freezing needs for
achieving cognitive closure.
PMID- 25111304
TI - Too young to correct: a developmental test of the three-stage model of social
inference.
AB - The 3-stage model of social inference posits that people categorize behaviors and
characterize actors or situations effortlessly, but they correct these
characterizations with additional information effortfully. The current article
tests this model using developmental data, assuming that the less cognitively
demanding processes in the model (i.e., categorization, characterization) should
appear earlier in development, whereas the more demanding correction process
should not appear until later in development. Using 2 different paradigms,
Studies 1 and 3 found that younger children failed to take situational
information into account while characterizing the actor. Study 2 found that
younger children failed to take dispositional information into account while
characterizing the situation. In contrast, in these 3 studies, older children
used the available information to correct their characterizations of the actors
and of the situations. Consistent with the 3-stage model, during elementary
school years, children start to integrate additional information when drawing
explicit social inferences. In Study 4, children of all age levels used a prior
expectancy to draw a dispositional inference, ignoring situational information,
suggesting that characterizations based on prior expectancies about an actor are
a highly efficient process, not contemplated by the model. The 4 studies together
illustrate how developmental data can be valuably used to test adult socio
cognitive models, to extend their validity, or to simply further inform those
models.
PMID- 25111305
TI - Mutual reinforcement between neuroticism and life experiences: a five-wave, 16
year study to test reciprocal causation.
AB - High neuroticism predicts psychopathology and physical health problems.
Nongenetic factors, including major life events and experiences, explain
approximately half of the variance in neuroticism. Conversely, neuroticism also
predicts these life experiences. In this study, we aimed to quantify the
reciprocal causation between neuroticism and life experiences and to gauge the
magnitude and persistence of these associations. This longitudinal cohort study
included 5 assessment waves over 16 years in a random sample of 296 Dutch
participants (47% women) with a mean age of 34 years (SD = 12, range 16-63
years). Neuroticism was assessed with the Amsterdam Biographic Questionnaire. The
experiences measured included positive and negative life events, long-term
difficulties (LTDs), and change in life quality, all assessed by contextual
rating procedures adapted from the Life Event and Difficulties Schedule. We fit
structural equation models in Mplus. Results showed that neuroticism consistently
predicted negative experiences, decreased life quality, and LTDs (beta = 0.15 to
0.39), whereas effects on positive experiences were variable (beta = 0.14). LTDs
and deteriorated life quality each predicted small but persistent increases in
neuroticism (beta = 0.18), whereas improved life quality predicted small but
persistent decreases (beta = -0.13). This suggests set point change in
neuroticism. Life event aggregates showed no persistent effects on the
neuroticism set point. Neuroticism and life experiences showed persistent,
bidirectional associations. Experience-driven changes in neuroticism lasted over
a decade. Results support the corresponsive principle (reciprocal causation),
suggesting a mixed model of change in neuroticism that distinguishes temporary
changes in neuroticism from persistent changes in an individual's neuroticism set
point.
PMID- 25111307
TI - Evaluation of the ecotoxicity of sediments from Yangtze river estuary and
contribution of priority PAHs to ah receptor--mediated activities.
AB - In this study, in vitro bioassays were performed to assess the ecotoxicological
potential of sediments from Yangtze River estuary. The cytotoxicity and aryl
hydrocarbon receptor (AhR)-mediated toxicity of sediment extracts with rainbow
trout (Oncorhynchus mykiss) liver cells were determined by neutral red retention
and 7-ethoxyresorufin-O-deethylase assays. The cytotoxicity and AhR-mediated
activity of sediments from the Yangtze River estuary ranged from low level to
moderate level compared with the ecotoxicity of sediments from other river
systems. However, Yangtze River releases approximately 14 times greater water
discharge compared with Rhine, a major river in Europe. Thus, the absolute
pollution mass transfer of Yangtze River may be detrimental to the environmental
quality of estuary and East China Sea. Effect-directed analysis was applied to
identify substances causing high dioxin-like activities. To identify unknown
substances contributing to dioxin-like potencies of whole extracts, we
fractionated crude extracts by open column chromatography. Non-polar paraffinic
components (F1), weakly and moderately polar components (F2), and highly polar
substances (F3) were separated from each crude extract of sediments. F2 showed
the highest dioxin-like activities. Based on the results of mass balance
calculation of chemical toxic equivalent concentrations (TEQs), our conclusion is
that priority polycyclic aromatic hydrocarbons indicated a low portion of bio
TEQs ranging from 1% to 10% of crude extracts. Further studies should be
conducted to identify unknown pollutants.
PMID- 25111308
TI - Meta-analysis of apolipoprotein E gene polymorphism and susceptibility of
myocardial infarction.
AB - A number of case-control studies have been conducted to clarify the association
between ApoE polymorphisms and myocardial infarction (MI); however, the results
are inconsistent. This meta-analysis was performed to clarify this issue using
all the available evidence. Searching in PubMed retrieved all eligible articles.
A total of 33 studies were included in this meta-analysis, including 18752 MI
cases and 18963 controls. The pooled analysis based on all included studies
showed that the MI patients had a decreased frequency of the epsilon2 allele (OR
= 0.78, 95% CI = 0.70-0.87) and an increased frequency of the epsilon4 allele (OR
= 1.15, 95% CI = 1.10-1.20); The results also showed a decreased susceptibility
of MI in the epsilon2epsilon3 vs. epsilon3epsilon3 analysis (OR = 0.79, 95% CI =
0.68-0.90) and in the epsilon2 vs. epsilon3 analysis (OR = 0.78, 95% CI = 0.69
0.89), an increased susceptibility of MI in the epsilon3epsilon4 vs.
epsilon3epsilon3 analysis (OR = 1.26, 95% CI = 1.12-1.41), in the epsilon4 vs.
epsilon3 analysis (OR = 1.22, 95% CI = 1.12-1.32) and in the epsilon4epsilon4 vs.
epsilon3epsilon3 analysis (OR = 1.59, 95% CI = 1.15-2.19). However, there were no
significant associations among polymorphisms and MI for the following genetic
models: frequency of the epsilon3 allele (OR = 0.99, 95% CI = 0.96-1.02);
epsilon2epsilon2 vs. epsilon3epsilon3 analysis (OR = 0.73, 95% CI = 0.40-1.32);
or epsilon2epsilon4 vs. epsilon3epsilon3 analysis (OR = 1.10, 95% CI = 0.99
1.21). Our results suggested that the epsilon4 allele of ApoE is a risk factor
for the development of MI and the epsilon2 allele of ApoE is a protective factor
in the development of MI.
PMID- 25111310
TI - New insight into the role of gold nanoparticles in Au@CdS core-shell
nanostructures for hydrogen evolution.
PMID- 25111309
TI - Low-intensity pulsed ultrasound induces angiogenesis and ameliorates left
ventricular dysfunction in a porcine model of chronic myocardial ischemia.
AB - BACKGROUND: Although a significant progress has been made in the management of
ischemic heart disease (IHD), the number of severe IHD patients is increasing.
Thus, it is crucial to develop new, non-invasive therapeutic strategies. In the
present study, we aimed to develop low-intensity pulsed ultrasound (LIPUS)
therapy for the treatment of IHD. METHODS AND RESULTS: We first confirmed that in
cultured human endothelial cells, LIPUS significantly up-regulated mRNA
expression of vascular endothelial growth factor (VEGF) with a peak at 32-cycle
(P<0.05). Then, we examined the in vivo effects of LIPUS in a porcine model of
chronic myocardial ischemia with reduced left ventricular ejection fraction
(LVEF) (n = 28). The heart was treated with either sham (n = 14) or LIPUS (32
cycle with 193 mW/cm2 for 20 min, n = 14) at 3 different short axis levels. Four
weeks after the treatment, LVEF was significantly improved in the LIPUS group
(46+/-4 to 57+/-5%, P<0.05) without any adverse effects, whereas it remained
unchanged in the sham group (46+/-5 to 47+/-6%, P = 0.33). Capillary density in
the ischemic region was significantly increased in the LIPUS group compared with
the control group (1084+/-175 vs. 858+/-151/mm2, P<0.05). Regional myocardial
blood flow was also significantly improved in the LIPUS group (0.78+/-0.2 to
1.39+/-0.4 ml/min/g, P<0.05), but not in the control group (0.84+/-0.3 to 0.97+/
0.4 ml/min/g). Western blot analysis showed that VEGF, eNOS and bFGF were all
significantly up-regulated only in the LIPUS group. CONCLUSIONS: These results
suggest that the LIPUS therapy is promising as a new, non-invasive therapy for
IHD.
PMID- 25111311
TI - Recovering metric properties of objects through spatiotemporal interpolation.
AB - Spatiotemporal interpolation (STI) refers to perception of complete objects from
fragmentary information across gaps in both space and time. It differs from
static interpolation in that requirements for interpolation are not met in any
static frame. It has been found that STI produced objective performance
advantages in a shape discrimination paradigm for both illusory and occluded
objects when contours met conditions of spatiotemporal relatability. Here we
report psychophysical studies testing whether spatiotemporal interpolation allows
recovery of metric properties of objects. Observers viewed virtual triangles
specified only by sequential partial occlusions of background elements by their
vertices (the STI condition) and made forced choice judgments of the object's
size relative to a reference standard. We found that length could often be
accurately recovered for conditions where fragments were relatable and formed
illusory triangles. In the first control condition, three moving dots located at
the vertices provided the same spatial and timing information as the virtual
object in the STI condition but did not induce perception of interpolated
contours or a coherent object. In the second control condition oriented line
segments were added to the dots and mid-points between the dots in a way that did
not induce perception of interpolated contours. Control stimuli did not lead to
accurate size judgments. We conclude that spatiotemporal interpolation can
produce representations, from fragmentary information, of metric properties in
addition to shape.
PMID- 25111312
TI - Controlling catalytic selectivity on metal nanoparticles by direct
photoexcitation of adsorbate-metal bonds.
AB - Engineering heterogeneous metal catalysts for high selectivity in thermal driven
reactions typically involves the synthesis of nanostructures with well-controlled
geometries and compositions. However, inherent relationships between the
energetics of elementary steps limit the control of catalytic selectivity through
these approaches. Photon excitation of metal catalysts can induce chemical
reactivity channels that cannot be accessed using thermal energy, although the
potential for targeted activation of adsorbate-metal bonds is limited because the
processes of photon absorption and adsorbate-metal bond photoexcitation are
typically separated spatially. Here, we show that the use of sub-5-nanometer
metal particles as photocatalysts enables direct photoexcitation of hybridized
adsorbate-metal states as the dominant mechanism driving photochemistry.
Activation of targeted adsorbate-metal bonds through direct photoexcitation of
hybridized electronic states enabled selectivity control in preferential CO
oxidation in H2 rich streams. This mechanism opens new avenues to drive selective
catalytic reactions that cannot be achieved using thermal energy.
PMID- 25111313
TI - Learning curves for robot-assisted and laparoscopic partial nephrectomy.
AB - OBJECTIVES: To evaluate the learning curve of robot-assisted partial nephrectomy
(RAPN) and laparoscopic partial nephrectomy (LPN) between two surgeons at a
single institution. METHODS: A prospectively maintained, Institutional Review
Board (IRB)-approved kidney surgery database was reviewed retrospectively and the
first 116 consecutive LPNs performed by one surgeon (Hyung Kim) and 116
consecutive RPNs performed by a second surgeon (Thomas Schwaab) were identified.
The learning curve was evaluated by examining the operative times, warm ischemia
times (WITs), estimated blood loss, the postoperative estimated glomerular
filtration rate (eGFR), and intra- and postoperative complications in the
quartiles of 29 patients. The LPNs performed by Hyung Kim were done following
completion of a minimally invasive fellowship. Thomas Schwaab had minimal
experience with LPN and no fellowship training before starting RAPN. RESULTS: The
RAPN and LPN groups had similar patient and tumor characteristics. The RAPN group
had a higher preoperative eGFR (74.1+/-22.04 vs. 80.95+/-21.25 mL/minutes,
p=0.015) and a worse Eastern Cooperative Oncology Group (ECOG) performance status
(ECOG 1+ in 12% vs. 2.6%, p<0.001) compared with the LPN group. Rates of
intraoperative (p=0.203) and postoperative (p=0.193) complications were similar.
In the RAPN group, operating room (OR) time (161+/-51 vs. 203+/-55 minutes,
p<0.001) and WIT (17.7+/-14.8 vs. 21.8+/-9.1 minutes, p<0.001) were shorter.
Postoperative stay was longer in the RAPN group (2.4+/-2.2 vs. 1.67+/-1.1 days,
p<0.001). The percentage decrease in postoperative eGFR was lower in the RAPN
group versus the LPN (9.6% vs. 10%). The learning curves differed for log tumor
size, log WIT, and postoperative complications. CONCLUSIONS: The variables of the
learning curve for RAPN can be obtained earlier than the same variables for LPN.
RAPN had a shorter OR time and WITs. The shorter WITs, earlier in the series, led
to consistently lower fluctuations in GFR and preservation of the renal function.
The learning curves for each procedure need to be re-evaluated at longer
intervals to ensure their accuracy.
PMID- 25111314
TI - A 3D aligning method for stimulated emission depletion microscopy using
fluorescence lifetime distribution.
AB - Optimal resolution by stimulated emission depletion (STED) microscopy requires
precise alignment of the donut-shaped depletion focus to the excitation focus. In
this article, we demonstrate that fluorescence lifetime distribution can be
implemented to align the STED system. Different from the traditional aligning
methods in which a scattering imaging module is often equipped, the lifetime
based method is free from probable mismatches between the scattering mode and the
fluorescent mode, drift errors caused by separate imaging and complex fitting
methods. Based on this method, a spatial resolution of 38 nm by time-gated
detection has been achieved.
PMID- 25111315
TI - New regulatory paradigms for innovative drugs to treat pediatric diseases.
PMID- 25111316
TI - Estimation of sodium and potassium intakes assessed by two 24 h urine collections
in healthy Japanese adults: a nationwide study.
AB - Excess Na intake and insufficient K intake are well-known risk factors for CVD.
International comparative studies have reported that Japan has the highest intake
of Na and the lowest intake of K in the world. However, no recent study has
precisely assessed Na and K intakes in Japanese adults. In the present study, Na
and K intakes were estimated from two 24 h urine collections implemented in
twenty-three out of forty-seven prefectures in Japan. Apparently healthy men (n
384) and women (n 376), aged 20 to 69 years, who had been working in welfare
facilities were recruited, with data collection conducted in February and March
2013. The mean Na excretion was 206.0 mmol/d in men and 173.9 mmol/d in women.
The respective values of K excretion were 51.6 and 47.2 mmol/d. The excretion of
both Na and K varied considerably among the prefectures, and was higher in
subjects with a higher BMI. In contrast, only K excretion was associated with
age. After estimating the usual intakes of Na and K, it was found that none of
the male subjects met the recommended Na intake values of the WHO, and that only
3.2 % met those of the Japanese government. The respective values for females
were 0.1 and 5.0 %. For K intake, 7.5 % of the total subjects met the recommended
values of the WHO and 21.7 % met those of the Japanese government. These findings
suggest that there is an urgent need for the development of an effective
intervention programme to reduce Na intake and promote K intake in the Japanese
population.
PMID- 25111317
TI - New drugs and treatment targets in psoriasis.
AB - In recent years, the increased understanding of the pathophysiology of psoriasis
has resulted in several new treatments. The success of ustekinumab proved the
importance of the IL-23/T helper cell 17 axis in psoriatic diseases. Several new
biologics targeting this axis will reach the clinic in the next years. Biologics
are costly, require injections, and some patients experience tacaphylaxis, thus,
the development of orally available, small-molecule inhibitors is desirable.
Among small-molecules under investigation are A3 adenosine receptor agonists,
Janus kinase inhibitors, and phosphodiesterase inhibitors. We review published
clinical trials, and conference abstracts presented during the last years,
concerned with new drugs under development for the treatment of psoriasis. In
conclusion, our psoriasis armamentarium will be filled with several new effective
therapeutic options the coming years. We need to be aware of the limitations of
drug safety data when selecting new novel treatments. Monitoring and clinical
registries are still important tools.
PMID- 25111318
TI - Peripartum cardiomyopathy: definition, incidence, etiopathogenesis, diagnosis,
and management.
AB - Peripartum cardiomyopathy (PPCM) is a serious pregnancy-associated disorder of
unknown etiology. The precise cellular and molecular mechanisms underlying PPCM
are unclear. A heightened awareness among health care providers can result in
early diagnosis of heart failure in late pregnancy and the early postpartum
period. Though the symptoms of dyspnea and fatigue can result from normal
physiologic changes during pregnancy, an electrocardiogram and brain natriuretic
peptide level should be obtained in these patients, in addition to baseline
laboratory tests such as a complete blood count, and basic metabolic and hepatic
function panels. If the electrocardiogram and brain natriuretic peptide level are
abnormal, an echocardiogram should be obtained. The role of endomyocardial biopsy
for the diagnosis of PPCM is controversial. Patients should be started on
diuretics if volume overloaded, and beta-blockers (preferably metoprolol) if no
contraindications exist; angiotensin-converting enzyme inhibitors and angiotensin
receptor blockers should be avoided during pregnancy or lactation. There are no
standard, universally accepted guidelines for the management of PPCM. Although
experimental therapies like bromocriptine, pentoxifylline and immunoglobulins
have shown promising results, large double-blind randomized trials are essential
to confirm the results of smaller studies. In patients with persistent severe
left ventricular (LV) dysfunction, advanced therapies like mechanical circulatory
support and heart transplantation should be considered. Owing to recent data
demonstrating deterioration of LV systolic function after initial recovery, it is
essential to maintain long-term follow up of these patients regardless of initial
recovery of LV function. We present a comprehensive review of the literature
etiopathogenesis, diagnosis, and management of PPCM.
PMID- 25111319
TI - Structural biology of cisplatin complexes with cellular targets: the adduct with
human copper chaperone atox1 in aqueous solution.
AB - Cisplatin is one of the most used anticancer drugs. Its cellular influx and
delivery to target DNA may involve the copper chaperone Atox1 protein. Although
the mode of binding is established by NMR spectroscopy measurements in solution
the Pt atom binds to Cys12 and Cys15 while retaining the two ammine groups-the
structural determinants of the adduct are not known. Here a structural model by
hybrid Car-Parrinello density functional theory-based QM/MM simulations is
provided. The platinated site minimally modifies the fold of the protein. The
calculated NMR and CD spectral properties are fully consistent with the
experimental data. Our in silico/in vitro approach provides, together with
previous studies, an unprecedented view into the structural biology of cisplatin
protein adducts.
PMID- 25111320
TI - Synthesis of 8-methyl-1-tetralone, a potential intermediate for (+/-)
platyphyllide.
AB - An alternative method for the synthesis of the 8-methyl-1-tetralone from the
commercially available 5-methoxy-1-tetralone has been developed. The
transformation involves eight steps and affords an overall yield 25%.
PMID- 25111322
TI - Early recognition and treatment of pelvic fractures.
PMID- 25111321
TI - Is increased susceptibility to Balkan endemic nephropathy in carriers of common
GSTA1 (*A/*B) polymorphism linked with the catalytic role of GSTA1 in ochratoxin
a biotransformation? Serbian case control study and in silico analysis.
AB - Although recent data suggest aristolochic acid as a putative cause of Balkan
endemic nephropathy (BEN), evidence also exists in favor of ochratoxin A (OTA)
exposure as risk factor for the disease. The potential role of xenobiotic
metabolizing enzymes, such as the glutathione transferases (GSTs), in OTA
biotransformation is based on OTA glutathione adducts (OTHQ-SG and OTB-SG) in
blood and urine of BEN patients. We aimed to analyze the association between
common GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms and BEN susceptibility, and
thereafter performed an in silico simulation of particular GST enzymes
potentially involved in OTA transformations. GSTA1, GSTM1, GSTT1 and GSTP1
genotypes were determined in 207 BEN patients and 138 non-BEN healthy individuals
from endemic regions by polymerase chain reaction (PCR). Molecular modeling in
silico was performed for GSTA1 protein. Among the GST polymorphisms tested, only
GSTA1 was significantly associated with a higher risk of BEN. Namely, carriers of
the GSTA1*B gene variant, associated with lower transcriptional activation, were
at a 1.6-fold higher BEN risk than those carrying the homozygous GSTA1*A/*A
genotype (OR = 1.6; p = 0.037). In in silico modeling, we found four structures,
two OTB-SG and two OTHQ-SG, bound in a GSTA1 monomer. We found that GSTA1
polymorphism was associated with increased risk of BEN, and suggested, according
to the in silico simulation, that GSTA1-1 might be involved in catalyzing the
formation of OTHQ-SG and OTB-SG conjugates.
PMID- 25111323
TI - Anatomy of the left main coronary artery of particular relevance to ablation of
left atrial and outflow tract arrhythmias.
AB - BACKGROUND: Left main coronary artery (LMCA) damage is a rare but catastrophic
complication of cardiac ablation procedures. OBJECTIVE: The purpose of this study
was to describe the anatomic relationships of the LMCA to its adjacent structures
using analysis of computed tomographic coronary angiograms (CTCA). METHODS: We
studied 100 patients (55 males, age 51 +/- 10 years) who were investigated for
chest pain with CTCA. The relationships between the LMCA and adjacent structures
were described by analysis of 2-dimensional images and 3-dimensional
reconstructions. RESULTS: The LMCA coursed within 5 mm of the anterior left
atrial endocardium and/or base of left atrial appendage in 49% (within 2 mm in
17%) and from the pulmonary artery in 90% (within 2 mm in 43%). The LMCA was
within 5 mm of the right ventricular outflow tract in 1%. In 4% the LMCA coursed
inferiorly, remaining within 5 mm of the left aortic sinus of Valsalva at a
vertical distance >5 mm from the inferior margin of the LMCA ostium. CONCLUSION:
The LMCA is often intimately related to the anterior left atrium, left atrial
appendage base, and pulmonary artery and occasionally to the inferior part of the
left aortic sinus of Valsalva and thus is exposed to the risk of injury during
ablation in these areas. The LMCA is rarely close to the right ventricular
outflow tract.
PMID- 25111324
TI - Major predictors of fibrous adherences in transvenous implantable cardioverter
defibrillator lead extraction.
AB - BACKGROUND: Percutaneous removal of implantable cardioverter-defibrillator (ICD)
leads is a difficult procedure because of the consequence of massive fibrous
tissue growth along the lead. OBJECTIVE: The purpose of this study was to
describe the occurrence and location of fibrous adherences in ICD lead extraction
and to identify potential predictors among patient and lead characteristics.
METHODS: We studied 637 consecutive patients who underwent transvenous extraction
of 678 ICD leads from 1997 to 2013. RESULTS: Procedural success rate was 99%,
without major complications. Areas of adherence were found in the subclavian vein
(78%), innominate vein (65%), superior vena cava (66%), and heart (73%). Dwell
time, passive fixation, and dual-coil lead design were independently associated
with adherences. Dual-coil lead design was associated with adherences in the
innominate vein and superior vena cava, whereas coil treatment (eg, expandable
polytetrafluoroethylene-coated or medical adhesive back-filled strategies)
prevented adherences. Passive fixation mechanism was associated with adherences
in the heart. CONCLUSION: ICD leads, after long dwell-time, are affected by
fibrous adherences uniformly distributed along the lead course. Lead features
represent major predictors of the phenomenon. Careful lead selection is
recommended at the time of implantation to prevent adherences. In addition, lead
related risk stratification is mandatory before a transvenous extraction
procedure.
PMID- 25111325
TI - Second coupling interval of nonsustained ventricular tachycardia to distinguish
malignant from benign outflow tract ventricular tachycardias.
AB - BACKGROUND: Idiopathic ventricular tachycardia (VT) originating from the outflow
tract (OT) usually is considered a benign condition. In rare cases, patients with
OT-VT suffer from syncope or even sudden cardiac death. OT-VT is frequently
preceded by nonsustained VT (NSVT). OBJECTIVE: The purpose of this study was to
clarify if the ECG parameters of NSVTs could differentiate malignant from benign
OT-VT. METHODS: We retrospectively evaluated patients without structural heart
disease who had documented OT-NSVT on ECG. ECG parameters were compared between
patients with syncope, aborted sudden cardiac death, or ventricular fibrillation
(malignant group, n = 36) and patients without syncope (benign group, n = 40).
RESULTS: There were no differences with regard to age and gender between the
malignant and benign groups. On analysis of NSVT, the first coupling interval
(CI) of NSVT was comparable between the 2 groups (458 +/- 87 ms vs 485 +/- 95 ms,
P = .212). However, the second CI of NSVT beats was significantly shorter in the
malignant group (313 +/- 58 ms vs 385 +/- 83 ms, P < .0001). During 48-month
follow-up, the benign group had a significantly lower recurrence of clinical VT
than the malignant group (P = .046). The malignant group frequently had more than
1 focus of VT, whereas the benign group showed only a single focus (1.82 vs 1.09,
P = .023). CONCLUSION: The second CI of NSVT in the malignant group was
significantly shorter than that of the benign OT-VT group. Careful measurement of
the second CI of NSVT may help identify the malignant form of OT-VT, enabling
early treatment to prevent future cardiac events.
PMID- 25111326
TI - Time outside of therapeutic range in atrial fibrillation patients is associated
with long-term risk of dementia.
AB - BACKGROUND: The mechanisms behind the association of atrial fibrillation (AF) and
dementia are unknown. One possibility is that exposure to chronic microembolism
or microbleeds results in repetitive cerebral injury that is manifest by
cognitive decline. OBJECTIVE: The purpose of this study was to test the
hypothesis that AF patients with a low percentage of time in the therapeutic
range (TTR) are at higher risk for dementia due to under- or overanticoagulation.
METHODS: Patients anticoagulated with warfarin (target international normalized
ratio [INR] 2-3), managed by the Intermountain Healthcare Clinical Pharmacist
Anticoagulation Service with no history of dementia or stroke/transient ischemic
attack, were included in the study. The primary outcome was dementia incidence
defined by ICD-9 codes. Percent time in TTR was calculated using the method of
linear interpolation and stratified as >75%, 51%-75%, 26%-50%, and <=25%.
Multivariable Cox hazard regression was used to determine dementia incidence by
percentage categories of TTR. RESULTS: A total of 2605 patients (age 73.7 +/-
10.8 years, 1408 [54.0%] male) were studied. The CHADS2 score distribution was 0:
216 (8.3%); 1: 579 (22.2%); 2: 859(33.0%); 3: 708 (27.2%); and >=4: 243 (9.3%).
The percent TTR averaged 63.1 +/- 21.3, with percent INR <2.0: 25.6% +/- 17.9%
and percent INR >3.0: 16.2% +/- 13.6%. Dementia was diagnosed in 109 patients
(4.2%) (senile: 37 [1.4%]; vascular: 8 [0.3%]; Alzheimer: 64 (2.5%]). After
adjustment, decreasing categories of percent TTR were associated with increased
dementia risk (vs >75%): <25%: hazard ratio (HR) 5.34, P < .0001; 26%-50%: HR
4.10, P < .0001; and 51%-75%: HR = 2.57, P = .001. CONCLUSION: Quality of
anticoagulation management represented as percent TTR among AF patients without
dementia was associated with dementia incidence. These data support the
possibility of chronic cerebral injury as a mechanism that underlies the
association of AF and dementia.
PMID- 25111327
TI - If inhibition in the atrioventricular node by ivabradine causes rate-dependent
slowing of conduction and reduces ventricular rate during atrial fibrillation.
AB - BACKGROUND: If channels are functionally expressed in atrioventricular (AV) nodal
tissue. OBJECTIVE: The purpose of this study was to address whether the
prototypical If inhibitor, ivabradine, at clinically safe concentrations can slow
AV node conduction to reduce ventricular rate (VR) during atrial fibrillation
(AF). METHODS: Effects of ivabradine (0.1 mg/kg i.v. bolus) were studied in an
anesthetized Yorkshire pig (N = 7) model of AF and in isolated guinea pig hearts
(N = 7). RESULTS: Ivabradine reduced heart rate (P = .0001) without affecting
mean arterial pressure during sinus rhythm. The agent lengthened PR intervals in
a rate-dependent manner (P = .0009) by 14 +/- 2.7 ms (P = .003) and 25 +/- 3.0 ms
(P = .0004) and increased atrial-His (A-H) intervals in a rate-dependent manner
(P = .020) by 10 +/- 1.7 ms and 17 +/- 2.8 ms during pacing at 130 and 180 bpm,
respectively (both P = .0008). Similar rate-dependent effects were observed in
isolated guinea pig hearts. Ivabradine slowed VR during AF from 240 +/- 21 bpm to
211 +/- 25 bpm (P = .041). The ivabradine-induced increase in A-H interval was
inversely correlated with VR (r = -0.85, P = .03, at 130 bpm; r = -0.95, P =
.003, at 180 bpm). QT and HV intervals, AF dominant frequency (8.5 +/- 0.9 to 8.7
+/- 1.1 Hz, P = NS), mean arterial pressure, and left ventricular dP/dt (1672 +/-
222 to 1889 +/- 229 mm Hg/s, P = NS) during AF were unaffected. CONCLUSION:
Ivabradine's rate-dependent increase in A-H interval is highly correlated with VR
during AF. As dominant frequency was unaltered, AV node conduction slowing during
high nodal activation rates appears to be the main mechanism of ivabradine's VR
reduction. If inhibition in the AV node may provide a promising target to slow VR
during AF without depression in contractility.
PMID- 25111328
TI - Isolated polycystic morphology: Does it affect the IVF treatment outcomes?
AB - The aim of the current study was to compare women who have normal ovarian
ultrasonographic findings and women with ovulatory polycystic ovary (PCO), in
terms of IVF treatment outcome. The study was conducted at a tertiary referral
hospital and included 906 women who underwent IVF treatment. Of these, 224 of the
women had PCO (24.7%) and 682 of the women had normal ovarian morphology (75.3%)
at the time of ultrasonographic examination prior to IVF. The treatment outcomes
were compared between the two groups. In the PCO group, the number of oocytes at
the size of > 16 mm, the overall number of collected oocytes and the number of
fertilised oocytes were found to be significantly higher. Furthermore, the rates
of implantation, biochemical pregnancy and clinical pregnancy were significantly
higher in the PCO group (p < 0.05). The detection of PCO morphology on baseline
ultrasonography in IVF candidates may be associated with higher treatment
success.
PMID- 25111331
TI - Graphene/graphite sheet assisted growth of high-areal-density horizontally
aligned carbon nanotubes.
AB - We report a facile graphene/graphite sheet assisted CVD process for the synthesis
of high-areal-density HACNT arrays. Besides, some metal nanoparticles could eat
the graphene/graphite sheets, forming serpentine holes on the sheets in the early
stage, and finally leading to the precipitation of CNTs without an additional
carbon source.
PMID- 25111330
TI - Assessment of molecular testing in fine-needle aspiration biopsy samples: an
experience in a Chinese population.
AB - Fine-needle aspiration biopsy remains the mainstay for preoperative examination
of thyroid nodules; however, it does not provide a definite diagnosis in up to
25% of nodules. Considerable studies have been performed to identify molecular
markers to resolve this diagnostic dilemma. The aim of this study was to
establish the distribution and frequency of common genetic alterations in a
comprehensive set of benign and malignant thyroid nodules, and to determine the
feasibility and role of testing for a panel of genetic alterations in improving
the accuracy of cytology diagnosis in a Chinese population. This study was
conducted in 314 thyroid nodules comprising 104 papillary thyroid carcinomas, 13
suspicious nodules, 52 indeterminate nodules, and 145 benign nodules. Point
mutations and RET/PTC rearrangements, were evaluated by pyrosequencing and TaqMan
real-time PCR, respectively. After surgery, 115 nodules were confirmed as
conventional papillary thyroid carcinoma and 102 (88.70%) of these nodules
harbored either the BRAF(V600E) mutation (76.52%) or RET/PTC rearrangements
(12.17%). RAS mutation was found in 1 (33.33%) follicular thyroid carcinoma, 1
(14.29%) follicular thyroid adenoma and 4 (10%) goiter nodules. With cytology and
molecular testing, the diagnostic accuracy was further increased to 98.82% in
papillary thyroid carcinoma diagnosis, and was preoperatively increased to 76.92%
and 84.00%, respectively, in nodules with suspicious and indeterminate cytology.
In conclusion, molecular testing of a panel of genetic alterations in fine-needle
aspiration biopsy can be effectively performed in clinical practice. It enhances
the accuracy of cytology and is of particular value for indeterminate nodules in
the Chinese population.
PMID- 25111332
TI - How frustrated Lewis acid/base systems pass through transition-state regions: H2
cleavage by [tBu3P/B(C6F5)3].
AB - We investigate the transition-state (TS) region of the potential energy surface
(PES) of the reaction tBu3P + H2 + B(C6F5)3 -> tBu3P-H(+) + (-)H-B(C6F5)3 and the
dynamics of the TS passage at room temperature. Owing to the conformational
inertia of the phosphane???borane pocket involving heavy tBu3P and B(C6F5)3
species and features of the PES E(P???H, B???H | B???P) as a function of P???H,
B???H, and B???P distances, a typical reactive scenario for this reaction is a
trajectory that is trapped in the TS region for a period of time (about 350 fs on
average across all calculated trajectories) in a quasi-bound state (scattering
resonance). The relationship between the timescale of the TS passage and the
effective conformational inertia of the phosphane???borane pocket leads to a
prediction that isotopically heavier Lewis base/Lewis acid pairs and normal
counterparts could give measurably different reaction rates. Herein, the
predicted quasi-bound state could be verified in molecular collision experiments
involving femtosecond spectroscopy.
PMID- 25111333
TI - The relative contribution of edema and hemorrhage to raised intrathecal pressure
after traumatic spinal cord injury.
AB - Raised intrathecal pressure (ITP) after traumatic spinal cord injury (SCI) is a
critically important aspect of injury development that may result in
significantly greater tissue damage and worsened functional outcome. Raised ITP
is caused by the accumulation of blood and/or water (edema), and while their
occurrence after traumatic SCI has been well established, the relative
contribution of both processes to the development of ITP after SCI has not yet
been determined. Accordingly, the current study investigates the temporal profile
of raised ITP after traumatic SCI in relation to both hemorrhage and edema
development. A closed balloon compression injury was induced at T10 in New
Zealand White rabbits. Animals were thereafter assessed for spinal water content
(edema), ITP, lesion and hemorrhage volume, and albumin immunoreactivity from 5 h
to 1 week post-SCI. Early increases in ITP at 5 h post-injury were associated
with significant increases in blood volume. ITP, however, was maximal at 3 days
post-SCI, at which time there was an associated significant increase in edema
that persisted for 1 week. We conclude that raised ITP after traumatic SCI is
initially driven by volumetric increases in hemorrhage, while edema becomes the
primary driver of ITP at 3 days post-injury.
PMID- 25111334
TI - Nrf2 augments skeletal muscle regeneration after ischaemia-reperfusion injury.
AB - Skeletal muscles harbour a resident population of stem cells, termed satellite
cells (SCs). After trauma, SCs leave their quiescent state to enter the cell
cycle and undergo multiple rounds of proliferation, a process regulated by MyoD.
To initiate differentiation, fusion and maturation to new skeletal muscle fibres,
SCs up-regulate myogenin. However, the regulation of these myogenic factors is
not fully understood. In this study we demonstrate that Nrf2, a major regulator
of oxidative stress defence, plays a role in the expression of these myogenic
factors. In both promoter studies with myoblasts and a mouse model of muscle
injury in Nrf2-deficient mice, we show that Nrf2 prolongs SC proliferation by up
regulating MyoD and suppresses SC differentiation by down-regulating myogenin.
Moreover, we show that IL-6 and HGF, both factors that facilitate SC activation,
induce Nrf2 activity in myoblasts. Thus, Nrf2 activity promotes muscle
regeneration by modulating SC proliferation and differentiation and thereby
provides implications for tissue regeneration.
PMID- 25111335
TI - Extinction and reinstatement of phasic dopamine signals in the nucleus accumbens
core during Pavlovian conditioning.
AB - The prediction-error model of dopamine (DA) signaling has largely been confirmed
with various appetitive Pavlovian conditioning procedures and has been supported
in tests of Pavlovian extinction. Studies have repeatedly shown, however, that
extinction does not erase the original memory of conditioning as the prediction
error model presumes, putting the model at odds with contemporary views that
treat extinction as an episode of learning rather than unlearning of
conditioning. Here, we combined fast-scan cyclic voltammetry (FSCV) with
appetitive Pavlovian conditioning to assess DA release directly during extinction
and reinstatement. DA was monitored in the nucleus accumbens core, which plays a
key role in reward processing. Following at least 4 daily sessions of 16 tone
food pairings, fast-scan cyclic voltammetry was performed while rats received
additional tone-food pairings followed by tone alone presentations (i.e.,
extinction). Acquisition memory was reinstated with noncontingent presentations
of reward and then tested with cue presentation. Tone-food pairings produced
transient (1- to 3-s) DA release in response to tone. During extinction, the
amplitude of the DA response decreased significantly. Following presentation of 2
noncontingent food pellets, subsequent tone presentation reinstated the DA
signal. Our results support the prediction-error model for appetitive Pavlovian
extinction but not for reinstatement.
PMID- 25111337
TI - The role of the medial prefrontal cortex in regulating interanimal coordination
of movements.
AB - Rats with juvenile play experience display a greater ability in coordinating
their movements with social partners than those deprived of such experience, and
this may be due to the play-induced neural restructuring of the medial prefrontal
cortex (mPFC). The present study investigates the role of the mPFC in interanimal
coordination. Rats with and without bilateral mPFC lesions were tested on a
robbing-and-dodging task. This food protection task measures the ability of rats
to protect pieces of food by gaining and maintaining an interanimal distance
between themselves and the rat attempting to rob the food. Given that mPFC
lesions have been associated with sensory and motor deficits, the same rats were
also subjected to a task to measure skilled motor movements. Rats with bilateral
mPFC lesions had more food stolen and displayed an inability to maintain
interanimal distance with partner, but did not exhibit any motor or sensory
deficits. These findings suggest that the mPFC is involved in interanimal
coordination and that the play-induced neural restructuring of this area may
account for the enhanced coordination seen in rats with prior play experience.
PMID- 25111336
TI - Age-related spatial working memory deficits in homing pigeons (Columba livia).
AB - The hippocampus is particularly susceptible to age-related degeneration that,
like hippocampal lesions, is thought to lead to age-related decline in spatial
memory and navigation. Lesions to the avian hippocampal formation (HF) also
result in impaired spatial memory and navigation, but the relationship between
aging and HF-dependent spatial cognition is unknown. To investigate possible age
related decline in avian spatial cognition, the current study investigated
spatial working memory performance in older homing pigeons (10+ years of age).
Pigeons completed a behavioral procedure nearly identical to the delayed spatial,
win-shift procedure in a modified radial arm maze that has been previously used
to study spatial working memory in rats and pigeons. The results revealed that
the older pigeons required a greater number of choices to task completion and
were less accurate with their first 4 choices as compared to younger pigeons (1-2
years of age). In addition, older pigeons were more likely to adopt a stereotyped
sampling strategy, which explained in part their impaired performance. To the
best of our knowledge, this study is the first to demonstrate an age-related
impairment of HF-dependent, spatial memory in birds. Implications and future
directions of the findings are discussed.
PMID- 25111338
TI - Ferro- to antiferromagnetic crossover angle in diphenoxido- and carboxylato
bridged trinuclear Ni(II)2-Mn(II) complexes: experimental observations and
theoretical rationalization.
AB - Three new trinuclear heterometallic Ni(II)-Mn(II) complexes have been synthesized
using a [NiL] metalloligand, where H2L = N,N'-bis(salicylidene)-1,3
propanediamine. The complexes [(NiL)2Mn(OCnn)2(CH3OH)2].CH3OH (1),
[(NiL)2Mn(OPh)2(CH3OH)2][(NiL)2Mn(OPh)2].H2O (2), and
[(NiL)2Mn(OSal)2(CH3OH)2].2[NiL] (3) (where OCnn = cinnamate, OPh =
phenylacetate, OSal = salicylate) have been structurally characterized. In all
three complexes, in addition to the double phenoxido bridge, the two terminal
Ni(II) atoms are linked to the central Mn(II) by means of a syn-syn bridging
carboxylate, giving rise to a linear structure. Complexes 1 and 2 with Ni-O-Mn
angles of 97.24 and 96.43 degrees , respectively, exhibit ferromagnetic
interactions (J(Ni-Mn) = +1.38 and +0.50 cm(-1), respectively), whereas 3 is
antiferromagnetic (J(Ni-Mn) = -0.24 cm(-1)), having an Ni-O-Mn angle of 98.51
degrees . DFT calculations indicate that there is a clear magneto-structural
correlation between the Ni-O-Mn angle and J(Ni-Mn) values, which is in agreement
with the experimental results.
PMID- 25111340
TI - Structural studies of nonionic dodecanol ethoxylates at the oil-water interface:
effect of increasing head group size.
AB - The conformation of charged surfactants at the oil-water interface was recently
reported. With the aim to assess the role of the head group size on the
conformation of the adsorbed layer, we have extended these studies to a series of
nonionic dodecanol ethoxylate surfactants (C12En, ethylene oxide units n from 6
to 12). The study was performed using neutron reflectometry to enable maximum
sensitivity to buried interfaces. Similarly to charged surfactants, the interface
was found to be broader and rougher compared to the air-water interface.
Irrespective of the head group size, the tail group region was found to assume a
staggered conformation. The conformations of the head group were found to be
significantly different from those of the air-water interface, moving from a
globular to an almost fully extended conformation at the oil-water interface. The
stretching of the head groups is attributed to the presence of some hexadecane
oil molecules, which may penetrate all the way to this region. It is proposed
here that the presence of the oil, which can efficiently solvate the surfactant
tail groups, plays a key role in the conformation of the adsorbed layer and is
responsible for the broadening of the interface.
PMID- 25111339
TI - Gender-dependent effects of maternal immune activation on the behavior of mouse
offspring.
AB - Autism spectrum disorders are neurodevelopmental disorders characterized by two
core symptoms; impaired social interactions and communication, and ritualistic or
repetitive behaviors. Both epidemiological and biochemical evidence suggests that
a subpopulation of autistics may be linked to immune perturbations that occurred
during fetal development. These findings have given rise to an animal model,
called the "maternal immune activation" model, whereby the offspring from female
rodents who were subjected to an immune stimulus during early or mid-pregnancy
are studied. Here, C57BL/6 mouse dams were treated mid-gestation with saline,
lipopolysaccharide (LPS) to mimic a bacterial infection, or
polyinosinic:polycytidylic acid (Poly IC) to mimic a viral infection. Autism
associated behaviors were examined in the adult offspring of the treated dams.
Behavioral tests were conducted to assess motor activity, exploration in a novel
environment, sociability, and repetitive behaviors, and data analyses were
carried independently on male and female mice. We observed a main treatment
effect whereby male offspring from Poly IC-treated dams showed reduced motor
activity. In the marble burying test of repetitive behavior, male offspring but
not female offspring from both LPS and Poly IC-treated mothers showed increased
marble burying. Our findings indicate that offspring from mothers subjected to
immune stimulation during gestation show a gender-specific increase in
stereotyped repetitive behavior.
PMID- 25111341
TI - Management of trichilemmal carcinoma: an update and comprehensive review of the
literature.
AB - BACKGROUND: Trichilemmal carcinoma (TC) is a rare malignant adnexal neoplasm with
outer root sheath differentiation. Most cases have been treated by surgical
excision with a few recurrences. There have been 6 case reports of TC treated
with Mohs micrographic surgery (MMS). OBJECTIVE: To perform an updated review of
the literature regarding management of this uncommon tumor. METHODS: A
comprehensive literature review was conducted by searching the PubMed database
using the keywords trichilemmal carcinoma, tricholemmal carcinoma, and
tricholemmocarcinoma. RESULTS: There have been 103 reported cases of TC, and most
of these were treated with surgical excisions. Of the 35 cases with follow-up
data, 3 reported local recurrences and 1 had subsequent metastatic disease. There
are 6 cases of TC successfully treated with MMS without any recurrence. In
addition, we report the seventh case of TC successfully treated with MMS. Other
reported treatment modalities include imiquimod and excision with frozen
sections. Histopathologically, the distinction between TC and squamous cell
carcinoma with clear cell differentiation has been debated in the literature.
CONCLUSION: Trichilemmal carcinoma is a rare neoplasm that may behave
aggressively. The recommended treatment should be a complete surgical excision
with histologic confirmation of clear margins. In cases where tissue sparing or
cosmesis is important, MMS may be considered.
PMID- 25111342
TI - Statistical evaluation of dermoscopic features in basal cell carcinomas.
AB - BACKGROUND: Early detection of basal cell carcinoma (BCC) is of crucial
importance, as serious morbidity may result from undiagnosed tumor. OBJECTIVE: To
evaluate diagnostic significance (specificity, sensitivity, positive and negative
predictive value) of dermoscopic features in BCCs. METHODS: A prospective
observational study was conducted using contact polarized dermoscopy to evaluate
the presence of various dermoscopic features. Images were evaluated for a range
of dermoscopic colors, structures, and vessels. SETTING: Specialized University
Clinic. PATIENTS: A sample of 151 histopathologically verified BCCs was collected
from 116 patients (64 males and 52 females). The populations included
predominantly Caucasian individuals. MAIN OUTCOME MEASURES: The sensitivity,
specificity, positive and negative predictive values of the various dermoscopic
features seen in BCCs were calculated according to standard formulas. RESULTS:
The highest diagnostic value (specificity [Sp] = 100%, positive predictive value
[PPV] = 100%) for BCC had spoke-wheel areas, short fine telangiectasias, white
rosette, annular hypopigmentation, multiple erosions, and ulceration. Arborizing
vessels (Sp = 96%, PPV = 98%) and microvessels (Sp = 93%, PPV = 97%) had
significant diagnostic value for BCC. Annular distribution of telangiectatic
vessels (Sp = 96%), translucency (Sp = 93%), and multiple blue-gray globules (Sp
= 89%) had the same PPV of 95% for BCCs. Other dermoscopic features of this study
are not strongly associated with the diagnosis of BCC. CONCLUSION: Dermoscopic
features relevant for diagnosis of BCC have different diagnostic "weight."
Clinicians should have known the sensitivity and specificity of each relevant
feature before they can make an accurate dermoscopic diagnosis of BCC.
PMID- 25111343
TI - Dermoscopic features in different morphologic types of basal cell carcinoma.
AB - BACKGROUND: Many different phenotypic presentations of basal cell carcinoma (BCC)
are possible. OBJECTIVE: This study aims to highlight the similarities and
differences in dermoscopic features between different morphologic types of BCC.
METHODS: A prospective observational study was performed using contact polarized
dermoscopy to evaluate the presence of various dermoscopic features. Images were
evaluated for a range of dermoscopic colors, structures, and vessels. Features
were compared according to the histopathologic subtype. RESULTS: Of the 151 BCCs,
39.7% were nodular, 37.7% superficial, 13.9% ulcerated, 3.97% pigmented, 2.65%
morpheaform, and 1.99% infiltrative BCCs. The dermoscopic features that showed a
highly significant difference (p < .001) in distribution between various
histologic groups were large blue-gray ovoid nests, leaf-like areas, arborizing
vessels, short fine telangiectasias, annular distribution of telangiectatic
vessels, structureless hypopigmentation, annular hypopigmentation, translucency,
multiple erosions, and ulceration. A significant difference (p < .05) between
evaluated groups was found in structureless hyperpigmentation, arborizing
microvessels, milky red background, and pigment network. CONCLUSION: The results
of the study indicate that the combination of relevant dermoscopic features in
different morphologic types of BCC depends on the thickness of the tumor, and not
on its histologic nature. In addition, dermoscopy was shown to be not
particularly useful in identifying which BCCs are more aggressive.
PMID- 25111344
TI - History of laser ablation in pigmented basal cell carcinoma conceals classic
dermoscopic patterns.
AB - BACKGROUND: Some patients with pigmented basal cell carcinoma (pBCC) had a
history of laser ablation after misdiagnosis, which may conceal the dermoscopic
clues of malignancy. OBJECTIVE: The objective of this study was to investigate
the question of whether the classic and nonclassic dermoscopic patterns of BCCs
may be concealed by past laser ablation. METHODS: Classic and nonclassic
dermoscopic patterns were examined in 55 pBCC patients with a history of laser
ablation and another 150 control pBCC patients. RESULTS: All but 4 of the study
patients (92.3%) showed at least 1 classic pattern of BCC, whereas every control
patient showed more than 1 classic pattern (p = .995). Compared with the control
group, the detection rate of large blue/gray ovoid nests, multiple blue/gray
globules, and ulceration was found to be significantly decreased in the study
group (p < .05). However, 4 patients who lacked classic patterns showed at least
1 nonclassic pattern. CONCLUSION: Previous laser ablation in pBCC may conceal the
classic dermoscopic patterns by reducing the detection rate. Therefore, more
prudent and detailed dermoscopic monitoring is required in suspected cases of
pBCC, especially in patients with a history of laser ablation.
PMID- 25111345
TI - Reconstruction of the external auditory canal using the random flap technique and
laser Doppler evaluation.
AB - BACKGROUND: The external auditory canal is one of the most difficult sites to
reconstruct after tumor resection. In general, fascia transplantation is used to
reconstruct defects of the external auditory canal, but this method is associated
with scar formation and prolonged wound healing. Scar tissue might cause stenosis
in the external auditory canal and hypoacusis, and wound healing is further
delayed by radiation and chemotherapy. OBJECTIVE: To examine the safety of a
random flap for reconstruction of an external auditory canal based on blood flow
evaluation using a laser Doppler system. METHODS: Ten healthy volunteers were
enrolled in this study to compare blood flow in the face, back, and behind the
ear using a laser Doppler system. Two cases of external auditory canal
reconstruction are presented. RESULTS: Blood flow behind the ear was abundant
compared with that in the back. Blood flow in the face was higher than that
behind the ear or on the back. CONCLUSION: Blood flow in the random flap was
easily evaluated using the laser Doppler method. Based on our findings, we
propose the random flap to reconstruct the external auditory canal after tumor
resection.
PMID- 25111346
TI - Midface-lift with lateral orbicularis oculi flap excision or imbrication.
AB - BACKGROUND: The orbicularis oculi advancement midface-lift treats rhytides and
infraorbital grooves. The muscle flap smoothes the subciliary lid and cheek zone
but may produce contour abnormalities laterally. OBJECTIVE: To describe a
technique of orbicularis flap midface-lift with excision or imbrication of muscle
and to evaluate the results--to include characterizing the lateral contour
abnormalities--in a large series. MATERIALS AND METHODS: A total of 108 patients
received a primary aesthetic orbicularis advancement flap midface-lift. Two
masked observers scored each patient's result based on preoperative and
postoperative images. Patients also scored their satisfaction of the results of
their procedures. Patient age, sex, surgical technique specifics (i.e., excision
or imbrication), and complications were recorded. RESULTS: All patients had
favorable aesthetic improvement scores with no significant complications. In
patients who received orbicularis excision (N = 33), lateral hollowing occurred
in 3 patients; none desired correction. With an imbrication technique (N = 75),
lateral mounding occurred in 6 patients; 3 of these patients were treated with
elliptical excision. CONCLUSION: Orbicularis advancement midface-lifting was safe
and effective in rejuvenating the midface in this series. Aesthetic complications
were infrequent but include lateral hollowing when orbicularis is excised and
lateral mounding with muscle imbrication.
PMID- 25111347
TI - Combined use of monopolar radiofrequency and transdermal drug delivery in the
treatment of melasma.
AB - BACKGROUND: Melasma is a common acquired pigmentary disorder that has a
considerable psychological impact on the patient. The recurrent and refractory
nature of this condition makes it difficult for treatment. OBJECTIVE: We aim to
evaluate the efficacy and safety of a combined system that simultaneously uses
monopolar radiofrequency (RF) and transdermal drug delivery of phytocomplex
containing 1% kojic acid in the treatment of melasma. MATERIALS AND METHODS:
Fifty patients affected by melasma underwent 6 sessions of treatment at 1-week
intervals. The outcome was evaluated before treatment (T0) and 1 month (T1) and 6
months (T2) after treatment using the Melasma Area and Severity Index score, a
Mexameter, and Visioface devices for digital and ultraviolet computerized image
analysis of skin color. RESULTS: The image analysis showed that hyperpigmentation
was significantly reduced at T1 and T2 compared with baseline. Melasma Area and
Severity Index score, the average melanin score, and the average erythema values
showed a significant reduction. No side effects were observed or reported.
CONCLUSION: This study describes the first report of improvement in melasma
through the combined use of monopolar RF with transdermal delivery of
depigmenting agents. This could be a safe, tolerable, and effective alternative
tool for the treatment of melasma.
PMID- 25111348
TI - Treatment of skin laxity using multisource, phase-controlled radiofrequency in
Asians: visualized 3-dimensional skin tightening results and increase in elastin
density shown through histologic investigation.
AB - BACKGROUND: A new multisource phase-controlled radiofrequency (MPCRF) device is
widely used for skin tightening and rejuvenation in Asia. OBJECTIVE: To evaluate
the efficacy of MPCRF objectively and histologically. METHODS: An MPCRF device
with real-time impedance control was evaluated. Ten Japanese patients were
treated one side of the face, and the untreated side served as a control. Three
dimensional (3-D) imaging was performed to evaluate the posttreatment volume
change. An independent observer assessed the 3-D images. Histologic evaluations
of elastin were performed by Victoria Blue staining in 5 Japanese patients.
RESULTS: Objective assessments evaluated by a 3-D color schematic representation
showed improvement in skin laxity after the final treatment in all patients. The
treated side improved markedly compared with the untreated side; however, even
the untreated side slightly improved. The elastin density was significantly
increased compared with controls in all 5 Japanese patients (p = .0013). Induced
elastin appeared to be relatively thin elastic fibers without irregular elastic
fibers, such as solar elastosis. Side effects were not observed, and the patients
reported feeling comfortable throughout the study. CONCLUSION: Multisource phase
controlled radiofrequency treatments provide stimulation of elastin and skin
tightening results safely and effectively, and thus are beneficial for improving
skin laxity and rhytides.
PMID- 25111349
TI - Novel treatment of nail psoriasis using the intense pulsed light: a one-year
follow-up study.
AB - BACKGROUND: Pulsed dye laser has been used successfully in the treatment of nail
psoriasis. Intense pulsed light (IPL) has been used in the treatment of plaque
psoriasis using a 550-nm filter. OBJECTIVE: To study the efficacy of IPL in the
treatment of nail psoriasis. PATIENTS AND METHODS: Twenty patients with finger
and toe nail psoriasis were treated by IPL. Sessions were performed every 2 weeks
for a maximum of 6 months. The Nail Psoriasis Severity Index (NAPSI) score was
calculated at baseline and 1 month after the last treatment session. Follow-up
was performed at 1, 6, and 12 months. RESULTS: Patients received a mean of 8.63
+/- 3.6 IPL sessions. After treatment, there was significant improvement in the
nail bed and matrix (p < .0001), and in the NAPSI (p < .0001). Nail bed showed
improvement by 71.2%, whereas the nail matrix improvement was only 32.2%. The
total NAPSI was 82.4%. Patient follow-up revealed relapse in 3 patients after 6
months. CONCLUSION: Intense pulsed light is a promising effective modality of
treatment of nail psoriasis, which is easy to use, safe, and provide a long
period of remission. This was confirmed by the elicited clinical improvement,
NAPSI, and patient satisfaction.
PMID- 25111350
TI - Prevention of excessive endothelin-1 release in sclerotherapy: in vitro and in
vivo studies.
AB - BACKGROUND: The foam sclerotherapy technique has become one of the most commonly
used treatments for superficial venous insufficiency. Despite excellent results,
few visual/neurologic disturbances have been recently reported; their
pathogenesis is still debated but a correlation with endothelin-1 (ET-1) release
from the treated vein has been proposed. OBJECTIVE: The purpose of this work was
to evaluate the ET-1 release after sclerotherapy and to investigate the effects
of the anti-endothelin drug aminaphtone. METHODS AND MATERIALS: As in vitro
sclerotherapy model, an endothelial cell culture, mimicking vascular endothelium,
was pretreated with aminaphtone and exposed to detergents. Cell survival and ET-1
release were measured. In in vivo experiments, 45 rats, fed with different
aminaphtone-rich diets, were subjected to sclerotherapy, and the systemic ET-1
was measured. RESULTS: Aminaphtone cell exposure caused a statistically
significant reduction in ET-1 release, both before and after in vitro
sclerotherapy. Rats fed with aminaphtone showed a trend toward reduced mortality
and a significant decrease of ET-1 release after sclerotherapy. CONCLUSION: This
is the first study in which an anti-endothelin agent was able to cause a
significant reduction of ET-1 release during sclerotherapy. Although clinical
studies are required, these findings might advocate the use of anti-endothelin
agents in prophylaxis of neurologic or visual disturbances after sclerotherapy.
PMID- 25111351
TI - Efficacy of incobotulinumtoxinA for treatment of glabellar frown lines: a post
hoc pooled analysis of 2 randomized, placebo-controlled, phase 3 trials.
AB - BACKGROUND: Botulinum neurotoxin type A trials in aesthetic indications have used
differing efficacy parameters and responder definitions. OBJECTIVE: To analyze
the treatment efficacy and duration of incobotulinumtoxinA for glabellar frown
lines using pooled data from 2 large, Phase 3, placebo-controlled trials, and end
points similar to those used in previous botulinum neurotoxin type A studies.
MATERIALS AND METHODS: IncobotulinumtoxinA and placebo groups comprised 366 and
181 subjects, respectively. The efficacy of a single 20-U treatment of
incobotulinumtoxinA or placebo was evaluated by investigator-assessed and subject
assessed responder rates (>= 1-point improvement from baseline), mean score, and
mean change from the baseline glabellar frown line severity score. RESULTS: At
all follow-up visits, responder rates and mean change from the baseline score
(investigator-assessed and subject-assessed) were significantly greater for
incobotulinumtoxinA versus placebo (p < .0001). The maximum investigator-assessed
responder rate (93.1%) was achieved at Day 30 after treatment, when the mean
improvement on the 4-point facial wrinkle scale peaked at 1.88. Treatment effect
declined over time but the investigator-assessed responder rate was 45.7% at the
end of the study. CONCLUSION: Superiority of incobotulinumtoxinA over placebo for
treating glabellar frown lines was confirmed. IncobotulinumtoxinA achieved a
maximum responder rate of 93.1% and a long duration of treatment effect: 45.7% of
subjects showed efficacy at 120 days.
PMID- 25111352
TI - Quantifying soft tissue loss in the aging male face using magnetic resonance
imaging.
AB - BACKGROUND: Quantitative data on soft tissue aging of the face are scarce,
particularly in men. OBJECTIVE: Magnetic resonance imaging (MRI) was used to
quantify and compare facial soft tissue loss in men. MATERIALS AND METHODS: Two
thousand thirty-seven MRIs were screened and 30 male subjects were divided into
young, middle, and old-aged groups. A blinded radiologist measured temporal,
infraorbital, and medial and lateral cheek areas. RESULTS: The mean thickness of
the subcutaneous tissue in the temporal area was 12.5, 10.9, and 9.6 mm in the
young, middle, and older age groups, respectively (p < .001). A 40% reduction in
the skin thickness was seen in the infraorbital areas. Finally, a decrease of 1.5
and 2.7 mm in medial cheeks (p < .001), and 0.9 and 1.6 mm (p = .03) in lateral
cheeks were measured in middle and old age groups. CONCLUSION: A steady and
significant decline in the soft tissue thickness was noted at all measured sites
in men over time. These findings are in contrast to our recently study in women
showing dramatic loss of soft tissue between the ages of 30 and 60 with no
significant differences between the middle and old-aged groups. These results
have implications for volume correction and maintenance of a youthful appearance
in the aging male face.
PMID- 25111353
TI - Trilobed flap for inferior-medial alar defect.
PMID- 25111354
TI - Commentary on the Trilobed flap for inferior-medial alar defect.
PMID- 25111355
TI - Response to onychodystrophy treated using fractional carbon dioxide laser therapy
and topical steroids.
PMID- 25111356
TI - An important mimicker: plaque-type syringoma mistakenly diagnosed as microcystic
adnexal carcinoma.
PMID- 25111357
TI - Chromophoric and dendritic phosphoramidites enable construction of functional
dendrimers with exceptional brightness and water solubility.
AB - The fluorescence brightness of a molecular probe determines whether it can be
effectively measured and its water solubility dictates if it can be applied in
real-world biological systems. However, molecules brighter than the most
efficient fluorescent dyes or particles brighter than quantum dots are hard to
come by, especially when they must also be soluble in water. In this report,
chromophoric phosphoramidites are used in a solid-state synthesis to construct
functional dendrimers. When highly twisted chromophores are chosen and the proper
spacers and dendrons are introduced, the resultant dendrimers emit exceptionally
bright fluorescence. Chromophores, spacers, and dendrons are stitched together by
efficient phosphoramidite reagents, which afford high-yield water-soluble
phosphodiester linkages after deprotection. The resulting water-soluble
dendrimers are exceptionally bright.
PMID- 25111358
TI - Geometric and redox flexibility of pyridine as a redox-active ligand that can
reversibly accept one or two electrons.
AB - A low-coordinate iron(I) species can reversibly reduce pyridine, either by one
electron to give a new C-C bond, or by two electrons to give a pyridine-derived
bridge with an unprecedented MU-eta(1):eta(3) binding mode.
PMID- 25111359
TI - Bacterial imprinting at Pickering emulsion interfaces.
AB - The tendency of bacteria to assemble at oil-water interfaces can be utilized to
create microbial recognition sites on the surface of polymer beads. In this work,
two different groups of bacteria were first treated with acryloyl-functionalized
chitosan and then used to stabilize an oil-in-water emulsion composed of cross
linking monomers that were dispersed in aqueous buffer. Polymerization of the oil
phase followed by removal of the bacterial template resulted in well-defined
polymer beads bearing bacterial imprints. Chemical passivation of chitosan and
cell displacement assays indicate that the bacterial recognition on the polymer
beads was dependent on the nature of the pre-polymer and the target bacteria. The
functional materials for microbial recognition show great potential for
constructing cell-cell communication networks, biosensors, and new platforms for
testing antibiotic drugs.
PMID- 25111360
TI - Theoretical exploration of the potential and force acting on one electron within
a molecule.
AB - The potential and force acting on one electron within a molecule (PAEM and FAEM)
have been investigated and analyzed. The PAEM, defined as the interaction energy
on one electron provided by all the nuclei and the remaining electrons in a
molecule, can be precisely expressed and calculated by ab initio method and our
in-house program. Although the analysis of the scalar function PAEM is similar to
that of the molecular electron density in the Bader's AIM theory, the former is
distinct from the latter mainly in three points: (a) The minus gradient of the
PAEM is the force acting on one electron within a molecule (FAEM). (b) The bond
center is defined in terms of the features of FAEM and PAEM between two bonded
atoms, and it is a two-dimensional attractive center whereas a nucleus is a three
dimensional attractive source for electrons. We have calculated the physical
quantities of one electron at the bond center, such as Dpb, the Hessian matrix,
and its eigenvalues. Interestingly, it is found that the force constant and
frequency of the electron interflow around the bond center are well correlated
with those corresponding quantities for the nuclear vibration which relate to the
bond strength, for some series of diatomic molecules. (c) The bond center locates
at a different point from that of the critical point of the electron density in
the Bader's AIM theory, which will lead to different partitioning of the
molecular space into the atomic regions.
PMID- 25111361
TI - [Conflicting Rules and Incentives for Health Promotion and Prevention in the
German Statutory Health Insurance (GKV)].
AB - OBJECTIVES: This study examines what role the German statutory health insurance
(GKV) has in health promotion and prevention, if regulations and incentives are
consistent, and if the politically-intended strengthening of prevention has been
achieved. METHODS: We compiled the regulations and incentives of the German
Sozialgesetzbuch V as the legal basis for health promotion and prevention of the
GKV and studied their effects and interactions. Using annual financial reports of
GKV we determined how the spending in prevention overall and in specific fields
of prevention has -developed. RESULTS: The responsibilities of the GKV in health
promotion and prevention lack a clear scientific foundation. Regulations have
been incrementally added following changing ideas in prevention and health
promotion policies. Currently, different norms and a variety of incentives lead
to inconsistent and conflicting aims. Only 2% of all expenditures of the GKV are
for health promotion and prevention, mainly spent for medical measures like
preventive medical check-ups or vaccination. While spending of the GKV in general
is rising, expenditures for prevention have decreased since 2009. CONCLUSIONS:
There is a need to harmonise the different regulations in health promotion and
prevention and to correct currently inconsistent incentives in the GKV. Given the
similar evidence base there seems to be no reason why responsibilities for health
promotion and primary, secondary or tertiary prevention should be regulated by
different normative constructs. Incentives should account for the different aims
of health insurers and their members. Financial incentives to increase spending
in prevention may be particularly effective when there is no short-term
financial interest for the health insurer.
PMID- 25111362
TI - [Which Factors Affect Weight Maintenance? A Qualitative Study with Adolescents
and their Parents who have Completed a Ten-months Intervention].
AB - BACKGROUND: The alarming increase in the prevalence of childhood obesity is
recognised as a major public health concern. Currently, structured multi-modal
therapy programmes present the gold standard of therapy strategies for obese
children and adolescents. However, effects of these treatments are still a matter
of discussion. Failure to isolate and understand the external and internal
factors contributing to successful, long-term weight reduction may well be
contributing to the ineffectiveness of current treatment interventions.
OBJECTIVE: A qualitative approach was chosen in order to identify subjectively
perceived resources and barriers to weight maintenance after previous weight
reduction. The research question focused on how these resources and barriers
affect success of participants. Additionally the question arose as to how and to
what extent parents should and could be involved in the therapy process. The
results can deliver important starting points for the development of therapy
programmes and future research. METHOD: 7 participants of a weight reduction and
maintenance programme and 7 of their parents were interviewed on their personal
experiences during and after the treatment. The interviews were analysed based on
the qualitative content analysis. RESULTS: Continuous motivation, especially
after the initial weight reduction phase, was identified as the strongest
predictor of successful weight maintenance. Successful weight maintainers
generally showed characteristics of higher self-efficacy, internal motivation
concerning physical activity and flexible self-control concerning food intake.
Unsuccessful weight gainers stated a lack of motivation concerning physical
activity and lost control over their eating habits. Concerning the role of
parents in the therapy process, the results show that higher parental involvement
does not predict greater success. The general relationship between parents and
their children seems to be more significant, especially concerning the issues of
responsibility. CONCLUSION: It is disputable to what extent the post treatment
intervention contributed to the development of intrinsic motivation. More
attention should be paid to the age (children or adolescents) of participants of
therapy programmes, especially concerning the involvement of parents. It is
assumed that general aspects of education should be discussed with parents.
PMID- 25111363
TI - Redifferentiation of dedifferentiated chondrocytes in a novel three-dimensional
microcavitary hydrogel.
AB - Although chondrocytes exist in native cartilage all over the body, it is still a
challenge to use them as therapeutic cells for cartilage tissue engineering (TE)
because of their easy dedifferentiation in in vitro culture. An improved culture
system to maintain the characteristics of chondrocytes or recover their
chondrocytic phenotype should be developed. In this study, we have set up an
innovative microcavitary alginate hydrogel in an easy way. We compared this
culture system with the conventional hydrogel and found that the microcavitary
hydrogel exhibited outstanding superiorities in helping the dedifferentiated
chondrocytes recover the capability for synthesizing cartilaginous extracellular
matrix. In addition, we explored the correlation between chondrocyte
redifferentiation in microcavitary hydrogels and changes in p38 and Erk1/2
activity. Our findings indicated that this microcavitary hydrogel would be a
promising culture system to provide sufficient competent cells for cartilage
regeneration and TE.
PMID- 25111364
TI - High prevalence of antineuronal antibodies in Tunisian psychiatric inpatients.
AB - The authors aimed to determine the prevalence of antineuronal antibodies in 103
psychiatric inpatients and 41 control subjects with no history of malignancies or
neurological disorders. All sera were tested by indirect immunofluorescence and
positive sera by immunoblot. Using immunofluorescence, antineuronal nuclear
autoantibodies were detected in 20 patients and none of the control subjects, and
antibodies reacted with the cytoplasm of Purkinje cells in six patients and two
control subjects. The immunoblot confirmed well-characterized antineuronal
antibodies only in five patients: two had anti-Ri and three had anti-Yo
antibodies. After a follow-up of 5 years, none of these patients developed
neurological disorder or malignancy.
PMID- 25111365
TI - Patients with mental-physical multimorbidity: do not let them fall by the
wayside.
PMID- 25111366
TI - Highly stable dye-sensitized solar cells based on novel 1,2,3-triazolium ionic
liquids.
AB - We describe the design and synthesis of novel low viscosity bicyclic 1,2,3
triazolium ionic liquids. These new salts are applied as nonvolatile electrolytes
in dye-sensitized solar cells, affording efficiencies up to 7.07% at low light
intensities, and 6.00% when illuminated at 100 mW cm(-2). The devices are highly
stable, retaining ca. 90% of their initial performance even after 1000 h of sun
testing at 60 degrees C. The results obtained with these new ionic liquids
compare very favorably to benchmark ionic liquid-based devices and illustrate the
potential of the triazolium family of salts to compete with their imidazolium
counterparts.
PMID- 25111367
TI - Characterization of rubella virus genotypes among pregnant women in northern
Vietnam, 2011-2013.
AB - Rubella virus (RV) infection is an unresolved clinical complication that affects
children in developing countries including Vietnam. RV infection during the first
trimester of pregnancy causes severe birth defects known as congenital rubella
syndrome. This study reports on the genomic characterization of RV strains
circulating in northern Vietnam during 2011-2013. RV-IgM positive amniotic fluid
specimens were collected from 38 women from northern Vietnam who presented with
clinical rubella at the National Hospital of Obstetrics and Gynecology in Hanoi,
Vietnam. The RV genes were determined by nested PCR with primers amplifying the
739-nucleotide coding region of the E1 gene. The sequences from the amplified DNA
fragments were phylogenetically analyzed and compared to reference RV strains.
Seventeen out of 38 samples are positive for RV detecting. All new RV isolates
are clustered to genotype 2B. Eighteen amino acid mutations were found in the T
and B cell epitopes. These results suggest that genotype 2B RV strains frequently
circulate in northern Vietnam. These data describe the RV genotype in Vietnam
with the aim of improving maternal and child health in this country.
PMID- 25111368
TI - Specific behavioral comorbidity in a large sample of children with functional
incontinence: Report of 1,001 cases.
AB - AIMS: Psychological comorbidity among children with functional incontinence is
high: 20-30% of children with nocturnal enuresis (NE), 20-40% of those with
daytime urinary incontinence (DUI) and 30-50% of those with fecal incontinence
(FI) have clinically relevant comorbid disorders. The aim of this study was to
analyze specific comorbid behavioral symptoms for different subtypes of
incontinence in a large group of children. METHODS: All 1,001 consecutive
children and adolescents (67.5% boys) with a mean age of 8.5 years presented at a
tertiary outpatient department between 2004 and 2011 were examined with a full
pediatric and child psychiatric assessment. Prevalence of different subforms of
incontinence and associated behavioral symptoms were analyzed. The internalizing,
externalizing, and total problem scores of the Child Behavior Checklist (CBCL)
were evaluated. RESULTS: Of all children, 70.1% (702 children) had NE, 36.1% (361
children) had DUI, and 36.8% (368 children) were affected by FI. More than 43% of
all children had clinically relevant psychological symptoms (CBCL total score,
cut-off at 90th percentile). Children with non-retentive FI had highest rates of
clinically relevant psychological symptoms (58.8%). Children with combined
subtypes of incontinence (any combination of NE, DUI, and FI) were more affected
by psychological comorbidities than children with isolated subtypes (NE or DUI or
FI). CONCLUSIONS: Children with incontinence have high rates of comorbid
behavioral symptoms-three to six times higher than norms. Especially children
with FI and combined subtypes of incontinence were affected. As behavioral
symptoms and disorders will interfere with incontinence treatment, a general
screening is recommended.
PMID- 25111369
TI - Neonatal lung function and therapeutics.
AB - Respiratory diseases are increasingly recognized as having their origins during
perinatal and early postnatal lung development, a time of significant adaptation
to large changes in redox conditions as well as to mechanical forces. This Forum
of the journal presents a Forum highlighting studies of the interplay between
reactive oxygen/nitrogen species and the systems that have evolved to degrade
them or exploit them, as well as the cellular repair processes which respond to
early life redox stress in the lung. This group of authors suggests new
understandings of these events that may point the way to improved therapeutic
approaches.
PMID- 25111371
TI - Randomized clinical trials and observational studies are more often alike than
unlike.
PMID- 25111372
TI - Copper(I) bromide catalyzed arylation of cyclic enamides and naphthyl-1
acetamides using diaryliodonium salts.
AB - Copper(I) bromide catalyzed direct C-H arylation of cyclic enamides was achieved
using diaryliodonium salts in the absence of base/additive at ambient temperature
with high yields. A biologically active dihydro[a]benzocarbazole scaffold was
synthesized using the established protocol. The scope of the current methodology
was further extended for the synthesis of C4-, C7-aryl-substituted 1-naphthyl
acetamides in good yields.
PMID- 25111370
TI - Diurnal floc generation from neuston biofilms in two contrasting freshwater
lakes.
AB - Selective adaptation of biofilm-forming bacteria to the nutrient-rich but
environmentally challenging conditions of the surface microlayer (SML) or neuston
layer was evident in littoral regions of two physically and geochemically
contrasting freshwater lakes. SML bacterial communities (bacterioneuston) in
these systems were depleted in Actinobacteria, enriched in either
Betaproteobacteria or Gammaproteobacteria, and either unicellular Cyanobacteria
were absent or microbial mat forming Cyanobacteria enriched relative to
communities in the underlying shallow water column (0.5 m depth). Consistent with
the occurrence of biofilm-hosted, geochemically distinct microhabitats, As-, Fe-,
and S-metabolizing bacteria including anaerobic taxa were detected only in the
SML in both systems. Over diurnal time scales, higher wind speeds resulted in the
generation of floc from SML biofilms, identifying a transport mechanism
entraining SML accumulated microorganisms, nutrients, and contaminants into the
underlying water column. The energy regime experienced by the SML was more
important to floc generation as larger flocs were more abundant in the larger,
oligotrophic lake (higher relative energy regime) compared to the sheltered,
smaller lake, despite relatively higher concentrations of bacteria, organic
carbon, Fe, and PO4(3-) in the latter system.
PMID- 25111373
TI - A novel angiotensin-I converting enzyme (ACE) inhibitory peptide from
gastrointestinal protease hydrolysate of silkworm pupa (Bombyx mori) protein:
Biochemical characterization and molecular docking study.
AB - Silkworm pupa (Bombyx mori) protein was hydrolyzed using gastrointestinal
endopeptidases (pepsin, trypsin and alpha-chymotrypsin). Then, the hydrolysate
was purified sequentially by ultrafiltration, gel filtration chromatography and
RP-HPLC. A novel ACE inhibitory peptide, Ala-Ser-Leu, with the IC50 value of
102.15MUM, was identified by IT-MS/MS. This is the first report of Ala-Ser-Leu
from natural protein. Lineweaver-Burk plots suggest that the peptide is a
competitive inhibitor against ACE. The molecular docking studies revealed that
the ACE inhibition of Ala-Ser-Leu is mainly attributed to forming very strong
hydrogen bonds with the S1 pocket (Ala354) and the S2 pocket (Gln281 and His353).
The results indicate that silkworm pupa (B. mori) protein or its gastrointestinal
protease hydrolysate could be used as a functional ingredient in auxiliary
therapeutic foods against hypertension.
PMID- 25111374
TI - Downregulation of natriuretic peptide system and increased steroidogenesis in rat
polycystic ovary.
AB - Atrial natriuretic peptide (ANP) is known to regulate ovarian functions, such as
follicular growth and steroid hormone production. The aim of the present study
was to investigate the natriuretic peptide system in a rat model of chronic
anovulation, the rat polycystic ovary. Adult female Wistar rats received a single
subcutaneous injection of 2mg estradiol valerate to induce polycystic ovaries,
while the control group received vehicle injection. Two months later, their
ovaries were quickly removed and analyzed. Polycystic ovaries exhibited marked
elevation of testosterone and estradiol levels compared to control ovaries. The
levels of ANP and the expression of ANP mRNA were highly reduced in the
polycystic ovaries compared to controls. By immunohistochemistry, polycystic
ovaries showed weaker ANP staining in stroma, theca cells and oocytes compared to
controls. Polycystic ovaries also had increased activity of neutral
endopeptidase, the main proteolytic enzyme that degrades natriuretic peptides.
ANP receptor C mRNA was reduced and ANP binding to this receptor was absent in
polycystic ovaries. Collectively, these results indicate a downregulation of the
natriuretic peptide system in rat polycystic ovary, an established experimental
model of anovulation with high ovarian testosterone and estradiol levels.
Together with previous evidence demonstrating that ANP inhibits ovarian
steroidogenesis, these findings suggest that low ovarian ANP levels may
contribute to the abnormal steroid hormone balance in polycystic ovaries.
PMID- 25111375
TI - Explaining educational disparities in adiposity: the role of neighborhood
environments.
AB - OBJECTIVE: To examine the extent to which characteristics of the neighborhood
built environment explain the association between adiposity and educational
qualifications in Australian women. METHODS: A community sample of 1,819 women
(aged 18-66) from the Melbourne SESAW study provided information regarding their
body mass index (BMI) and level of education. Objective measures of participants'
residential neighborhood built environments were obtained using a Geographic
Information System. RESULTS: Compared with women with a high school degree or
above, women who did not complete high school had higher average BMI, which was
partially explained by lower density of sports facilities and living less
proximally to the coastline and to supermarkets. In a multiple mediator model,
which explained 16.6% of the educational disparity in BMI, the number of sports
facilities and presence of the coastline within 2 km of participants' homes were
significant mediators of the observed socioeconomic disparity in BMI.
CONCLUSIONS: The residential neighborhood environment may help to explain
socioeconomic patterning of overweight and obesity in Australian women. These
results provide further support for considering the built environment in obesity
prevention initiatives, suggesting a potential role in decreasing social
inequalities in obesity.
PMID- 25111376
TI - Down-modulation of Bcl-2 sensitizes PTEN-mutated prostate cancer cells to
starvation and taxanes.
AB - BACKGROUND: The critical role of PTEN in regulating the PI3K/Akt/mTOR signaling
pathway raises the possibility that targeting downstream effectors of the PI3K
pathway, such as Bcl-2, might be an effective anti-proliferative strategy for
PTEN-deficient prostate cancer cells. METHODS: Four prostate cancer cell lines
(LNCaP, PC3, DU145, 22Rv1) were assayed for their levels of total Akt and Ser473
phosphorylated Akt (p-Akt) by Western Blotting; their growth rates and
sensitivity to different doses of paclitaxel were determined by cell counts after
Trypan Blue dye exclusion assay. Cells were subjected to different combinations
of starvation (growth factors and/or aminoacids withdrawal), paclitaxel treatment
and Bcl-2 silencing by siRNA. Cell viability was evaluated by Trypan Blue dye
exclusion assay, Propidium Iodide (PI) and Annexin-V/PI staining. RESULTS: We
assessed the sensitivity of different prostate cancer cell lines to starvation
and we observed a differential response correlated to the levels of Akt
activation. The four prostate cancer cell lines also showed different sensitivity
to taxol treatments; LNCaP and 22Rv1 cells were more resistant to paclitaxel than
DU145 and PC3 cells. Combining taxol with growth factors and aminoacids
deprivation leaded to a more than additive reduction of cell viability compared
to single treatments in PTEN-mutant LNCaP cells. Down-modulation of anti
apoptotic Bcl-2 protein by siRNA sensitized LNCaP cells to taxanes and starvation
induced cell death. CONCLUSIONS: Silencing Bcl-2 in PTEN-mutated prostate cancer
cells enhances the apoptotic effects of combined starvation and taxol treatments,
indicating that inhibition of Bcl-2 may be of significant value in PTEN-mutant
tumor therapy.
PMID- 25111377
TI - Oncofetal signaling as a target for cancer therapy.
PMID- 25111379
TI - Evidence-based psychological interventions and the common factors approach: the
beginnings of a rapprochement?
AB - Laska, Gurman, and Wampold (2014, pp. 467-481) argue that common factors (CFs)
have largely been ignored by clinical researchers developing research-based
interventions but that CFs are primarily responsible for therapeutic change. On
the contrary, many clinical researchers developing empirically supported
treatments have been studying the contribution of these factors for decades. What
has been demonstrated is that these factors are contributory, but are not
sufficient to produce maximum effects and their impact differs greatly from
disorder to disorder. But we also take note of a change of tone and perhaps
substance from these authors on the contribution of CFs to evidence-based
psychological interventions, and reflect on recent changes in our own views both
of which may reduce differences in our respective positions.
PMID- 25111378
TI - Blockade of IL-36 receptor signaling does not prevent from TNF-induced arthritis.
AB - INTRODUCTION: Interleukin (IL)-36alpha is a newly described member of the IL-1
cytokine family with a known inflammatory and pathogenic function in psoriasis.
Recently, we could demonstrate that the receptor (IL-36R), its ligand IL-36alpha
and its antagonist IL-36Ra are expressed in synovial tissue of arthritis
patients. Furthermore, IL-36alpha induces MAP-kinase and NFkappaB signaling in
human synovial fibroblasts with subsequent expression and secretion of pro
inflammatory cytokines. METHODS: To understand the pathomechanism of IL-36
dependent inflammation, we investigated the biological impact of IL-36alpha
signaling in the hTNFtg mouse. Also the impact on osteoclastogenesis by IL
36alpha was tested in murine and human osteoclast assays. RESULTS: Diseased mice
showed an increased expression of IL-36R and IL-36alpha in inflamed knee joints
compared to wildtype controls. However, preventively treating mice with an IL-36R
blocking antibody led to no changes in clinical onset and pattern of disease.
Furthermore, blockade of IL-36 signaling did not change histological signs of TNF
induced arthritis. Additionally, no alteration on bone homeostasis was observed
in ex vivo murine and human osteoclast differentiation assays. CONCLUSION: Thus
we conclude that IL-36alpha does not affect the development of inflammatory
arthritis.
PMID- 25111380
TI - Use of relational strategies to repair alliance ruptures: How responsive
supervisors train responsive psychotherapists.
AB - Inasmuch as therapist responsiveness is the crucial ingredient in psychotherapy
success, teaching supervisees to be optimally responsive to their clients is the
primary function of supervision. Responsive supervision is particularly critical
when a trainee experiences a faltering or problematic working alliance with a
client. In this article, I describe and illustrate how supervisors can work
responsively, both explicitly (through instruction) and implicitly (through
modeling) when their supervisees report a serious alliance rupture. Next, I
illustrate, with the same case example, how quickly ruptures in the therapeutic
alliance can lead to ruptures in the supervisory alliance when the supervisor is
not sufficiently responsive to the trainee's needs and, instead, relies
exclusively on case management. Throughout the article, I discuss how the
construct of responsiveness fits within the substantial body of theory and
research on relational processes in supervision.
PMID- 25111381
TI - Common factors are not so common and specific factors are not so specified:
toward an inclusive integration of psychotherapy research.
AB - The dichotomy between what has been termed empirically supported treatments (EST)
and common factors (CF) is false and counterproductive. Neither has a monopoly on
empirical truth. The term nonspecific is unproductive and misleading. Specified
versus nonspecified is more empirically correct. Assumptions of the EST and CF
approaches are questionable. Common factors (both currently specified and not so
specified) are reviewed. These include the therapeutic relationship,
expectancies, attributions for therapeutic success, exposure, and mastery. Far
from maximizing therapeutic success, the CF EST dichotomy and its resulting
theoretical squabbles result in weaker outcomes than would be the case if
empirical results were taken seriously, and factors shown to be effective (both
specified and nonspecified) were systematically investigated and integrated so as
to create maximally effective treatments.
PMID- 25111382
TI - Crystal structures of PRK1 in complex with the clinical compounds lestaurtinib
and tofacitinib reveal ligand induced conformational changes.
AB - Protein kinase C related kinase 1 (PRK1) is a component of Rho-GTPase, androgen
receptor, histone demethylase and histone deacetylase signaling pathways
implicated in prostate and ovarian cancer. Herein we describe the crystal
structure of PRK1 in apo form, and also in complex with a panel of literature
inhibitors including the clinical candidates lestaurtinib and tofacitinib, as
well as the staurosporine analog Ro-31-8220. PRK1 is a member of the AGC-kinase
class, and as such exhibits the characteristic regulatory sequence at the C
terminus of the catalytic domain--the 'C-tail'. The C-tail fully encircles the
catalytic domain placing a phenylalanine in the ATP-binding site. Our inhibitor
structures include examples of molecules which both interact with, and displace
the C-tail from the active site. This information may assist in the design of
inhibitors targeting both PRK and other members of the AGC kinase family.
PMID- 25111383
TI - 18F-glutathione conjugate as a PET tracer for imaging tumors that overexpress L
PGDS enzyme.
AB - Lipocalin-type prostaglandin D synthase (L-PGDS) has been correlated with the
progression of neurological disorders. The present study aimed at evaluating the
imaging potency of a glutathione conjugate of fluorine-18-labeled fluorobutyl
ethacrynic amide ([18F]FBuEA-GS) for brain tumors. Preparation of [18F]FBuEA-GS
has been modified from the -4-tosylate derivative via radiofluorination in 5%
radiochemical yield. The mixture of nonradioactive FBuEA-GS derived from a
parallel preparation has be resolved to two isomers in a ratio of 9:1 using
analytic chiral reversed phase high performance liquid chromatography (RP-HPLC).
The two fluorine-18-labeled isomers purified through nonchiral semipreparative RP
HPLC as a mixture were studied by assessing the binding affinity toward L-PGDS
through a gel filtration HPLC, by analyzing radiotracer accumulation in C6 glioma
cells, and by evaluating the imaging of radiotracer in a C6 glioma rat with
positron emission tomography. The inhibition percentage of the production of PGD2
from PGH2 at the presence of 200 uM of FBuEA-GS and 4-Dibenzo[a,d]cyclohepten-5
ylidene-1-[4-(2H-tetrazol-5-yl)butyl]piperidine (AT-56) were 74.1 +/- 4.8% and
97.6 +/- 16.0%, respectively. [18F]FBuEA-GS bound L-PGDS (16.3-21.7%) but not the
isoform, microsomal prostaglandin E synthase 1. No binding to GST-alpha and GST
pi was observed. The binding strength between [18F]FBuEA-GS and L-PGDS has been
evaluated using analytic gel filtration HPLC at the presence of various
concentrations of the cold competitor FBuEA-GS. The contrasted images indicated
that the radiotracer accumulation in tumor lesions is probably related to the
overexpression of L-PGDS.
PMID- 25111384
TI - Enhanced anti-tumor effect of zoledronic acid combined with temozolomide against
human malignant glioma cell expressing O6-methylguanine DNA methyltransferase.
AB - Temozolomide (TMZ), a DNA methylating agent, is widely used in the adjuvant
treatment of malignant gliomas. O6-methylguanine-DNA methyltranferase (MGMT), a
DNA repair enzyme, is frequently discussed as the main factor that limits the
efficacy of TMZ. Zoledronic acid (ZOL), which is clinically applied to treat
cancer-induced bone diseases, appears to possess direct anti-tumor activity
through apoptosis induction by inhibiting mevalonate pathway and prenylation of
intracellular small G proteins. In this study, we evaluated whether ZOL can be
effectively used as an adjuvant to TMZ in human malignant glioma cells that
express MGMT. Malignant glioma cell lines, in which the expression of MGMT was
detected, did not exhibit growth inhibition by TMZ even at a longer exposure.
However, combination experiment of TMZ plus ZOL revealed that a supra-additive
effect resulted in a significant decrease in cell growth. In combined TMZ/ZOL
treatment, an increased apoptotic rate was apparent and significant activation of
caspase-3 and cleavage of poly-(ADP-ribose) polymerase were observed compared
with each single drug exposure. There were decreased amounts of Ras-GTP, MAPK and
Akt phosphorylation and MGMT expression in the ZOL-treated cells. Subcutanous
xenograft models showed significant decrease of tumor growth with combined
TMZ/ZOL treatment. These results suggest that ZOL efficaciously inhibits activity
of Ras in malignant glioma cells and potentiates TMZ-mediated cytotoxicity,
inducing growth inhibition and apoptosis of malignant glioma cells that express
MGMT and resistant to TMZ. Based on this work, combination of TMZ with ZOL might
be a potential therapy in malignant gliomas that receive less therapeutic effects
of TMZ due to cell resistance.
PMID- 25111385
TI - Bipolar vaporization, resection, and enucleation versus open prostatectomy:
optimal treatment alternatives in large prostate cases?
AB - OBJECTIVES: The study compared the transurethral resection in saline (TURis),
transurethral vaporization in saline (TUVis), bipolar plasma enucleation of the
prostate (BPEP), and open prostatectomy (OP) in a single-center, prospective,
randomized controlled clinical setting exclusively involving large prostate
patients. PATIENTS AND METHODS: During a 41/2 year enrollment period, 320 cases
of prostate volume over 80 mL, maximum flow rate (Qmax) below 10 mL/second,
International Prostate Symptom Score (IPSS) over 19, or urinary retention were
included in the trial and equally randomized in the four study arms. Patients
were assessed preoperatively as well as at the 1-, 3-, 6-, and 12-month follow-up
checkups using the IPSS, quality of life (QoL) score, Qmax, postvoiding residual
urinary volume (PVR), and prostate-specific antigen (PSA). RESULTS: Similar
preoperative parameters were established in the four series. OP and BPEP were
characterized by resembling operating times, while TURis and TUVis displayed
prolonged surgical durations. TURis emphasized a substantially decreased mean
resected tissue weight. TUVis showed the lowest mean hemoglobin level drop,
followed by TURis and BPEP (equivalent results) and finally OP (highest
bleeding). OP described the longest mean catheterization period and hospital
stay, followed by TURis, and afterward by TUVis and BPEP (similar data). During
the follow-up period, statistically equivalent IPSS, QoL, Qmax, and PVR outcomes
were established for OP, BPEP, and TURis. TUVis displayed significantly smaller
Qmax improvements, but similar other functional features. Significantly lower
mean PSA levels were determined secondary to OP and BPEP when compared to bipolar
resection and subsequently to vaporization. CONCLUSIONS: OP and BPEP emphasized
the highest surgical efficiency (prolonged postoperative recovery for OP), while
TUVis displayed the lowest hemorrhagic risks. On the medium term, generally
resembling functional outcomes were determined for the four techniques, with
significantly decreased mean PSA values secondary to OP and BPEP.
PMID- 25111386
TI - Electron spin resonance of nitrogen-vacancy defects embedded in single
nanodiamonds in an ABEL trap.
AB - Room temperature optically detected magnetic resonance of a single quantum object
with nanoscale position control is an outstanding challenge in many areas,
particularly in the life sciences. We introduce a novel approach to control the
nitrogen-vacancy (NV) centers hosted in a single fluorescent nanodiamond (FND)
for which an anti-Brownian electrokinetic trap (ABEL) performs the position
control and an integrated radiofrequency (RF) circuit provides enhanced magnetic
flux density for ensemble spin-state control simultaneously. We demonstrate
static magnetic field sensing in platforms compatible with ABEL trap. With the
advances in the synthesis and functionalization of stable arbitrarily small FNDs,
we foresee the use of our device for the trapping and manipulation of single
molecular-sized FNDs in aqueous solution.
PMID- 25111387
TI - Methylation marker analysis and HPV16/18 genotyping in high-risk HPV positive
self-sampled specimens to identify women with high grade CIN or cervical cancer.
AB - OBJECTIVES: Methylation marker analysis using bi-marker panel MAL/miR-124-2 is a
promising triage test for identifying cervical (pre)cancer in high-risk human
papillomavirus (hrHPV) positive women. Bi-marker panel MAL/miR-124-2 can be
applied directly on self-sampled cervico-vaginal material and its sensitivity is
non-inferior to that of cytology, yet at the cost of more colposcopy referrals.
Our objective was to increase specificity of MAL/miR-124-2 methylation analysis
by varying the assay thresholds and adding HPV16/18 genotyping. METHODS: 1019
hrHPV-positive women were selected from a randomized controlled self-sampling
trial (PROHTECT-3; 33-63 years, n=46,001) and nine triage strategies with
methylation testing of MAL/miR-124-2 and HPV16/18 genotyping were evaluated. The
methylation assay threshold was set at four different predefined levels which
correspond with clinical specificities for end-point cervical intra-epithelial
grade 3 or worse (CIN3+) of 50%, 60%, 70%, and 80%. RESULTS: The CIN3+
sensitivity of methylation analysis decreased (73.5 to 44.9%) while specificity
increased (47.2 to 83.4%) when increasing the assay threshold. CIN3+ sensitivity
and specificity of HPV16/18 genotyping were 68.0% and 65.6%, respectively.
Combined methylation analysis at threshold-80 and HPV16/18 genotyping yielded
similar CIN3+ sensitivity as that of methylation only at threshold-50 (77.6%)
with an increased specificity (54.8%). CONCLUSIONS: Combined triage by MAL/miR
124-2 methylation analysis with threshold-80 and HPV16/18 genotyping reaches high
CIN3+ sensitivity with increased specificity to identify women with cervical
(pre)cancer among HPV self-sample positive women. The combined strategy is
attractive as it is fully molecular and identifies women at the highest risk of
cervical (pre)cancer because of strongly elevated methylation levels and/or
HPV16/18 positivity.
PMID- 25111389
TI - Thermoresponsive poly(N-isopropylacrylamide)/graphene/Au nanocomposite hydrogel
for water treatment by a laser-assisted approach.
AB - The thermoresponsive poly(N-isopropylacrylamide)/graphene/Au multicomponent
hydrogel is prepared by the simultaneous in-situ formation of Au nanoparticles
and the reduction of graphene oxide, assisted by NIR laser irradiation of a
prefabricated PNIPAM/GO hydrogel with auric acid precursor, showing great
potential for water treatment owing to the excellent photothermal effect.
PMID- 25111391
TI - Treatment of Mycobacterium tuberculosis infection: time to get a move on?
PMID- 25111390
TI - Plasma levels of microRNA-499 provide an early indication of perioperative
myocardial infarction in coronary artery bypass graft patients.
AB - BACKGROUND: Recent studies indicated that microRNAs (miRNAs, miRs) were important
for many biological and pathological processes, and they might be potential
biomarkers for cardiovascular diseases. The present study aims to determine the
release patterns of miRNAs in cardiac surgery and to analyze the ability of miRs
to provide early prediction of perioperative myocardial infarction (PMI) in
patients undergoing coronary artery bypass graft (CABG) surgery.
METHODOLOGY/PRINCIPAL FINDINGS: Thirty on-pump CABG patients were recruited in
this study; and miR-499, miR-133a and miR-133b, cardiac troponin I (cTnI) were
selected for measurement. Serial plasma samples were collected at seven
perioperative time points (preoperatively, and 1, 3, 6, 12, 24, and 48 hours
after declamping) and were tested for cTnI and miRs levels. Importantly, miR
levels peaked as early as 1-3 hours, whereas cTnI levels peaked at 6 hours after
declamping. Peak plasma concentrations of miRs correlated significantly with cTnI
(miR-499, r = 0.583, P = 0.001; miR-133a, r = 0.514, P = 0.006; miR-133b, r =
0.437, P = 0.05), indicating the degree of myocardial damage. In addition, 30 off
pump CABG patients were recruited; miR-499 and miR-133a levels were tested, which
were significantly lower in off-pump group than in on-pump group. A prospective
cohort of CABG patients (n = 120) was recruited to study the predictive power of
miRs for PMI. The diagnosis of PMI strictly adhered to the principles of
universal definition of myocardial infarction. The data analysis revealed that
miR-499 had higher sensitivity and specificity than cTnI, and indicated that miR
499 could be an independent risk factor for PMI. CONCLUSION: Our results
demonstrate that circulating miR-499 is a novel, early biomarker for identifying
perioperative myocardial infarction in cardiac surgery.
PMID- 25111392
TI - Microbial community structure of relict niter-beds previously used for saltpeter
production.
AB - From the 16th to the 18th centuries in Japan, saltpeter was produced using a
biological niter-bed process and was formed under the floor of gassho-style
houses in the historic villages of Shirakawa-go and Gokayama, which are
classified as United Nations Educational, Scientific and Cultural Organization
(UNESCO) World Heritage Sites. The relict niter-beds are now conserved in the
underfloor space of gassho-style houses, where they are isolated from
destabilizing environmental factors and retain the ability to produce nitrate.
However, little is known about the nitrifying microbes in such relict niter-bed
ecosystems. In this study, the microbial community structures within nine relict
niter-bed soils were investigated using 454 pyrotag analysis targeting the 16S
rRNA gene and the bacterial and archaeal ammonia monooxygenase gene (amoA). The
16S rRNA gene pyrotag analysis showed that members of the phyla Proteobacteria,
Actinobacteria, Bacteroidetes, Chloroflexi, Firmicutes, Gemmatimonadetes, and
Planctomycetes were major microbial constituents, and principal coordinate
analysis showed that the NO3-, Cl-, K+, and Na+ contents were potential
determinants of the structures of entire microbial communities in relict niter
bed soils. The bacterial and archaeal amoA libraries indicated that members of
the Nitrosospira-type ammonia-oxidizing bacteria (AOB) and "Ca. Nitrososphaera"
type ammonia-oxidizing archaea (AOA), respectively, predominated in relict niter
bed soils. In addition, soil pH and organic carbon content were important factors
for the ecological niche of AOB and AOA in relict niter-bed soil ecosystems.
PMID- 25111393
TI - Population genomics of the fission yeast Schizosaccharomyces pombe.
AB - The fission yeast Schizosaccharomyces pombe has been widely used as a model
eukaryote to study a diverse range of biological processes. However, population
genetic studies of this species have been limited to date, and we know very
little about the evolutionary processes and selective pressures that are shaping
its genome. Here, we sequenced the genomes of 32 worldwide S. pombe strains and
examined the pattern of polymorphisms across their genomes. In addition to
introns and untranslated regions (UTRs), intergenic regions also exhibited lower
levels of nucleotide diversity than synonymous sites, suggesting that a
considerable amount of noncoding DNA is under selective constraint and thus
likely to be functional. A number of genomic regions showed a reduction of
nucleotide diversity probably caused by selective sweeps. We also identified a
region close to the end of chromosome 3 where an extremely high level of
divergence was observed between 5 of the 32 strains and the remain 27, possibly
due to introgression, strong positive selection, or that region being responsible
for reproductive isolation. Our study should serve as an important starting point
in using a population genomics approach to further elucidate the biology of this
important model organism.
PMID- 25111394
TI - Nowcasting the spread of chikungunya virus in the Americas.
AB - BACKGROUND: In December 2013, the first locally-acquired chikungunya virus
(CHIKV) infections in the Americas were reported in the Caribbean. As of May 16,
55,992 cases had been reported and the outbreak was still spreading.
Identification of newly affected locations is paramount to intervention
activities, but challenging due to limitations of current data on the outbreak
and on CHIKV transmission. We developed models to make probabilistic predictions
of spread based on current data considering these limitations. METHODS AND
FINDINGS: Branching process models capturing travel patterns, local infection
prevalence, climate dependent transmission factors, and associated uncertainty
estimates were developed to predict probable locations for the arrival of CHIKV
infected travelers and for the initiation of local transmission. Many
international cities and areas close to where transmission has already occurred
were likely to have received infected travelers. Of the ten locations predicted
to be the most likely locations for introduced CHIKV transmission in the first
four months of the outbreak, eight had reported local cases by the end of April.
Eight additional locations were likely to have had introduction leading to local
transmission in April, but with substantial uncertainty. CONCLUSIONS: Branching
process models can characterize the risk of CHIKV introduction and spread during
the ongoing outbreak. Local transmission of CHIKV is currently likely in several
Caribbean locations and possible, though uncertain, for other locations in the
continental United States, Central America, and South America. This modeling
framework may also be useful for other outbreaks where the risk of pathogen
spread over heterogeneous transportation networks must be rapidly assessed on the
basis of limited information.
PMID- 25111396
TI - (Phenoxyimidazolyl-salicylaldimine)iron complexes: synthesis, properties and iron
catalysed ethylene reactions.
AB - The reaction of 2-{[2-(1H-imidazol-4-yl)-ethylimino]-methyl}-phenol (L1), 2,4-di
tert-butyl-6-{[2-(1H-imidazol-4-yl)-ethylimino]-methyl}-phenol (L2) or 4-tert
butyl-2-{[2-(1H-imidazol-4-yl)-ethylimino]-methyl}-phenol (L3) with iron(ii)
precursors produced either iron(ii) or iron(iii) complexes, depending on the
nature of the anions in the iron(ii) precursor and the ligand. When the anion is
chloride and the ligand L1, the product is [(L1)2Fe][FeCl4] (1), but when the
anion is triflate (OTf(-)) and the ligand is L2, the product is [(L2)2Fe][OTf]2
(2). With iron(ii) halides and tert-butyl groups on the phenoxy ligands L2 and
L3, the iron(iii) complexes [(L2)FeX2] {where X = Cl (3), Br (4) and I = (5)} and
[(L3)FeCl2] (6) were formed. Complexes 1-6 were characterised by a combination of
elemental analyses, IR spectroscopy and mass spectrometry; and in selected cases
(3 and 4) by single crystal X-ray crystallography. The crystal structures of 3
and 4 indicated that the iron(ii) precursors oxidised to iron(iii) in forming
complexes 3-6; an observation that was corroborated by the magnetic properties
and the (57)Fe Mossbauer spectra of 3 and 4. The iron(iii) complexes 3-6 were
used as pre-catalysts for the oligomerisation and polymerisation of ethylene.
Products of these ethylene reactions depended on the solvent used. In toluene
ethylene oligomerised mainly to 1-butene and was followed by the 1-butene
alkylating the solvent to form butyl-toluenes via a Friedel-Crafts alkylation
reaction. In chlorobenzene, ethylene oligomerised mainly to a mixture of C4-C12
alkenes. Interestingly small amounts of butyl-chlorobenzenes and hexyl
chlorobenzenes were also formed via a Friedel-Crafts alkylation with butenes and
hexenes from the oligomerisation of ethylene.
PMID- 25111395
TI - Diphenyl diselenide and sodium selenite associated with chemotherapy in
experimental toxoplasmosis: influence on oxidant/antioxidant biomarkers and
cytokine modulation.
AB - SUMMARY The aim of this study was to assess the effect of
sulfamethoxazole/trimethoprim (ST) supplemented with diphenyl diselenide and
sodium selenite in experimental toxoplasmosis, on oxidant/antioxidant biomarkers
and cytokine levels. Eighty-four BALB/c mice were divided in seven groups: group
A (negative control), and groups B to G (infected). Blood and liver samples were
collected on days 4 and 20 post infection (p.i.). Levels of thiobarbituric acid
(TBA) reactive substances and advanced oxidation protein products (AOPP) were
assessed in liver samples. Both biomarkers were significantly increased in
infected groups on day 4 p.i., while they were reduced on day 20 p.i., compared
with group A. Glutathione reductase (GR) activity significantly (P<0.01)
increased on day 4 p.i., in group G, compared with group A. INF-gamma was
significantly increased (P<0.001) in both periods, day 4 (groups B, C, F and G)
and 20 p.i. (groups C, F and G). IL-10 significantly reduced (P<0.001) on day 4
p.i. in group B; however, in the same period, it was increased (P<0.001) in
groups C and G, compared with group A. On day 20 p.i., IL-10 increased (P<0.001)
in groups F and G. Therefore, our results highlighted that these forms of
selenium, associated with the chemotherapy, were able to reduce lipid
peroxidation and protein oxidation, providing a beneficial immunological balance
between the production of pro- and anti-inflammatory cytokines.
PMID- 25111397
TI - Rapidly developed neurosyphilis in a psoriasis patient under treatment with
infliximab: a case report.
PMID- 25111399
TI - National Association of Clinical Nurse Specialists news: Presidents message, June
2014.
PMID- 25111398
TI - Thermoresponsive copolymer/SiO2 nanoparticles with dual functions of thermally
controlled drug release and simultaneous carrier decomposition.
AB - The preparation of thermoresponsive drug carriers with a self-destruction
property is presented. These drug carriers were fabricated by incorporation of
drug molecules and thermoresponsive copolymer, poly(N-isopropylacrylamide-co
acrylamide), into silica nanoparticles in a one-pot preparation process. The
enhanced drug release was primarily attributed to faster molecule diffusion
resulting from the particle decomposition triggered by phase transformation of
the copolymer upon the temperature change. The decomposition of the drug carriers
into small fragments should benefit their fast excretion from the body. In
addition, the resulting drug-loaded nanoparticles showed faster drug release in
an acidic environment (pH 5) than in a neutral one. The controlled drug release
of methylene blue and doxorubicin hydrochloride and the self-decomposition of the
drug carriers were successfully characterized by using TEM, UV/Vis spectroscopy,
and confocal microscopy. Together with the nontoxicity and excellent
biocompatibility of the copolymer/SiO2 composite, the features of controlled drug
release and simultaneous carrier self-destruction provided a promising
opportunity for designing various novel drug-delivery systems.
PMID- 25111400
TI - Clinical Nurse Specialists National Survey.
PMID- 25111401
TI - The nurse's critical role in optimizing clinical documentation systems.
PMID- 25111402
TI - The need for increased sex and gender-based analysis/subanalysis in nursing and
medical research.
PMID- 25111403
TI - Prescribing with an empty pharmacy: drug shortages update for the clinical nurse
specialist.
PMID- 25111404
TI - Transdermal fentanyl for cancer pain.
PMID- 25111405
TI - Fundamentals of making a sale.
PMID- 25111406
TI - Preoperative factors affecting the intraoperative core body temperature in
abdominal surgery under general anesthesia: an observational cohort.
AB - PURPOSE: The study was conducted to identify preoperative factors affecting the
intraoperative core body temperature in abdominal surgery under general
anesthesia. DESIGN: This study was performed through prospective descriptive
research design. SETTING: The setting was a 1300-bed university hospital in
Incheon, South Korea. SAMPLES: The sample consisted of 147 patients who had
undergone elective abdominal surgery under general anesthesia. METHODS: Age,
weight, and height were collected on a preoperative visit to general unit, and
body mass index, body surface area, and total body fat were calculated. The basal
preoperative core body temperature (CBT), preoperative blood pressure, and heart
rate were measured. Core body temperature was again measured at 1, 2, and 3 hours
following general anesthesia. RESULTS: Predictive factors of intraoperative
hypothermia of less than 36 degrees C were preoperative CBT (beta = .44), weight
(beta = .41), preoperative heart rate (beta = .20), and age (beta = -.13) at 1
hour after anesthesia (R = 0.658, F = 68.3, P < .001); preoperative CBT (beta =
.33), weight (beta = .37), preoperative heart rate (beta = .22), and age (beta =
.24) at 2 hours after anesthesia (R = 0.631, F = 60.8, P < .001); and age (beta =
-.34), weight (beta = .36), preoperative CBT (beta = .30), and preoperative heart
rate (beta = .20) at 3 hours after anesthesia (R = 0.665, F = 70.6, P < .001).
CONCLUSION: Low preoperative body temperature and low weight seem to be risk
factors of intraoperative hypothermia during 2 hours after anesthesia and
advanced age and low weight at 3 hours following anesthesia. IMPLICATIONS: We
recommend prewarming and intraoperative warming through forced air warming
devices and covering a patient with a warm blanket during transportation. This
procedure is necessary for the abdominal surgical patients of advanced age with
low weight and duration of general anesthesia to last more than 1 hour.
PMID- 25111407
TI - Modeling the complex activity of sickle cell and thalassemia specialist nurses in
England.
AB - OBJECTIVE: Specialist advanced practice nursing in hemoglobinopathies has a rich
historical and descriptive literature. Subsequent work has shown that the role is
valued by patients and families and also by other professionals. However, there
is little empirical research on the complexity of activity of these services in
terms of interventions offered. In addition, the work of clinical nurse
specialists in England has been devalued through a perception of
oversimplification. PURPOSE: The purpose of this study was to understand the
complexity of expert nursing practice in sickle cell and thalassemia. DESIGN: The
approach taken to modeling complexity was used from common methods in
mathematical modeling and computational mathematics. Knowledge discovery through
data was the underpinning framework used in this study using a priori mined data.
This allowed categorization of activity and articulation of complexity. RESULT:
In total, 8966 nursing events were captured over 1639 hours from a total of 22.8
whole time equivalents, and several data sources were mined. The work of
specialist nurses in this area is complex in terms of the physical and
psychosocial care they provide. The nurses also undertook case management
activity such as utilizing a very large network of professionals, and others
participated in admission avoidance work and education of patients' families and
other staff. CONCLUSION: The work of nurses specializing in hemoglobinopathy care
is complex and multidimensional and is likely to contribute to the quality of
care in a cost-effective way. An understanding of this complexity can be used as
an underpinning to establishing key performance indicators, optimum caseload
calculations, and economic evaluation.
PMID- 25111408
TI - The relationship between uncontrolled glycemia and the cost of hospitalization.
AB - PURPOSE/OBJECTIVE: The purpose of this study was to examine the relationship
between hospitalization cost and discharge blood glucose levels among adult
diabetes mellitus type 2 patients hospitalized with uncontrolled glycemia without
complications. DESIGN: Retrospective cohort analysis examined healthcare billing
and laboratory data. SETTING: The study was performed in Chicago, Illinois, in a
269-bed medical center between January 1, 2011, and December 31, 2011. SAMPLE:
Patients were placed into 1 of 2 groups at discharge: blood glucose level less
than 250 mg/dL or blood glucose level 250 mg/dL or greater. RESULTS: Of the 579
patients with uncontrolled glycemia, 366 met inclusion criteria: diabetes
mellitus without complications (International Classification of Diseases, Ninth
Revision; 250.0) with abnormal fasting blood glucose (International
Classification of Diseases, Ninth Revision; 790.21). Discharge blood glucose
levels were 250 mg/dL or greater in 74 patients and less than 250 mg/dL in 292
patients. Mean age of the 2 cohorts was 71.4 (SD, 13.41) years. The majority was
male (52.1% and 59.7%, respectively). The median healthcare cost for the entire
sample was $3964.34. The mean cost of healthcare for the group with blood glucose
of 250 mg/dL or greater at discharge was $4182.65, with a mean length of stay of
8.22 (SD, 3.468) days, while the mean cost of healthcare for the group with blood
glucose of less than 250 mg/dL at discharge was $3826.25 and mean length of stay
7.826 (SD, 6.073) days. Analysis of cost was conducted using Pearson chi and was
significant for alpha = .05 (P = .037). The odds ratio of having increased
healthcare cost with blood glucose of 250 mg/dL or greater was 1.732 with a 95%
confidence interval of 0.998 to 3.012. CONCLUSION: The group discharged with
blood glucose levels of 250 mg/dL or greater accrued greater cost during
hospitalization than did patients who were discharged with blood glucose levels
of less than 250 mg/dL. IMPLICATIONS: Today's healthcare system is struggling
with cost containment, quality control, and standardization of care. Clinical
nurse specialists can evaluate current patient care practices and ensure that the
practice setting is fiscally beneficial to future patients and healthcare
organizations.
PMID- 25111409
TI - Characteristics, resource utilization, and nursing care of patients who undergo
percutaneous tracheostomy.
AB - PURPOSE/OBJECTIVES: Many critically ill patients require a tracheostomy when
unable to be weaned from prolonged ventilator support. This study describes the
characteristics, resource use, and outcomes of patients who required a
tracheostomy for failure to wean from mechanical ventilation. DESIGN: A
retrospective descriptive study was conducted to analyze data from the electronic
medical record and hospital databases. SETTING: The setting was a tertiary care
hospital with a level I trauma center. SAMPLE: Data from 363 adult subjects who
underwent a tracheostomy after prolonged mechanical ventilation during a 1-year
period were obtained from hospital databases. All underwent a percutaneous
procedure. The majority of subjects were male (62.8%) and white (57.9%), with a
median age of 59 years. Nearly half had a trauma diagnosis. RESULTS: Hospital
mortality was low (9.9%). Ventilator days, hospital/intensive care unit lengths
of stay, and costs were high. Only 7.1% of subjects were discharged directly from
the hospital to home. Others were transferred to long-term acute-care hospitals,
rehabilitation centers, skilled nursing facilities, and other hospitals. Those
who had the tracheostomy done prior to 10 days of ventilation had better
outcomes; however, these same subjects had lower acuity scores. Within 1 day of
the procedure, ventilator settings were reduced, airway pressures were lower, and
level of sedation was improved. CONCLUSIONS: Patients requiring a tracheostomy
incur high resource use, and although the majority was transferred to other
facilities, the number discharged directly home was low. Improved physiological
parameters and reduced ventilator settings following the tracheostomy facilitated
weaning from ventilation. IMPLICATIONS: Knowledge of characteristics and outcomes
may assist in identifying interventions to reduce the need for tracheostomy or
improve outcomes. In particular, the clinical nurse specialist can lead team
initiatives to promote weaning prior rather than performing a tracheostomy as
well as interventions postprocedure to improve discharge outcomes.
PMID- 25111410
TI - Clinical nurse specialist profile.
PMID- 25111411
TI - Where the heart is.
PMID- 25111412
TI - Impact of the clinical nurse specialist role on the costs and quality of
healthcare: policy briefing paper (December, 2013).
PMID- 25111413
TI - A new polyoxygenated cyclohexane and other constituents from Kaempferia rotunda
and their cytotoxic activity.
AB - The isolation of secondary metabolites from a methanolic extract of Kaempferia
rotunda yielded 12 compounds (1-12), including a new polyoxygenated cyclohexane
compound, (-)-3-acetyl-4-benzoyl-1-benzoyloxymethyl-1,6-diepoxycyclohexan-2,3,4,5
tetrol (1). The structures of the isolated compounds were determined based on
their spectroscopic data and comparison with references. All of the isolated
compounds were tested for their cytotoxic activity against pancreatic (PSN-1) and
breast (MDA-MB231) cancer cell lines. Compound 12 showed moderate cytotoxic
activity against PSN-1 and MDA-MB231 without showing any cytotoxicity against the
normal cell line, TIG-3.
PMID- 25111414
TI - [XVII Portuguese Congress of Rheumatology in a flash].
PMID- 25111415
TI - Infection and rheumatic diseases: cause, consequence or both?
PMID- 25111416
TI - Sclerostin and Dkk-1 in patients with ankylosing spondylitis.
AB - OBJECTIVE: To determine the serum Dickkopf-related protein 1 (Dkk-1) and
sclerostin levels, and their relationship to structural damage and disease
activity in patients with ankylosing spondylitis (AS), as well as to compare the
serum Dkk-1 and sclerostin levels in patients receiving and not receiving anti
TNF-a treatment. MATERIALS AND METHOds: This cross-sectional study included 44 AS
patients and 41 healthy age- and gender- -matched controls. Demographic data,
disease activity parameters, and Bath Ankylosing Spondylitis Radiologic Index
(BASRI) scores were recorded. Serum Dkk-1 and sclerostin levels were measured
using commercially available ELISA. RESULTS: Serum Dkk-1 levels were lower (P >
0.05) and sclerostin levels were significantly lower (P < 0.05) in the AS
patients than in the controls. Dkk-1 and sclerostin levels were similar in the
patients that did and didn't receive anti-TNF-a treatment, and in the patients
with active and inactive disease (P > 0.05). There wasn't a correlation between
serum Dkk-1 or sclerostin levels, and disease activity indices (P > 0.05). BASRI
scores did not correlate with serum Dkk-1 or sclerostin levels (P > 0.05).
DISCUSSIOn: Sclerostin expression is impaired in AS, but this is not the case for
Dkk-1. The lack of an association between Dkk-1 or sclerostin levels, and anti
TNF-a treatment, disease activity indices, and radiological damage might indicate
that neither the Dkk-1 nor sclerostin level induce inflammation and radiological
damage in AS patients. Pathologic bone formation in AS might be due to molecular
dysfunction of sclerostin and Dkk-1 at the cellular level.
PMID- 25111417
TI - Osteomyelitis and arthritis of the wrist caused by Mycobacterium intracellulare
in an immunocompetent patient: a case report and literature review.
AB - Mycobacterium intracellulare causes infection in humans. Involvement of joint and
bone, however, is extremely rare. We present the case of an immunocompetent 67
year-old female with chronic swelling of the wrist joint diagnosed as rheumatoid
arthritis by her previous physician. Examination revealed an unclosed fistula
associated with a puncture, and bone and joint destruction on radiographs. She
was diagnosed with osteomyelitis and arthritis due to M. intracellulare on
histological and microbiological examinations. She was successfully treated with
radical surgical debridement and anti-tuberculous drugs for 1 year and there was
no recurrence at 3 years postoperatively.
PMID- 25111418
TI - Condyloma acuminatum by human papilloma virus infection in childhood-systemic
lupus erythematosus patients.
AB - INTRODUCTION: Infections are frequent in childhood-systemic lupus erythematosus
(C-SLE) patients, including human papillomavirus (HPV). HPV infection may cause
genital and anal warts named condyloma acuminatum (CA). To our knowledge, none
case was reported and the prevalence of CA in C-SLE population was not performed.
CASE REPORTS: From January 1983 to May 2012, 5,682 patients were followed at the
Pediatric Rheumatology Unit from of our University Hospital and 289 (5%) of them
met the American College of Rheumatology classification criteria for C- SLE. Four
(1.4%) of our female patients had CA. The median age at diagnosis was 13 years.
Three of them were sexually active and all of them had active disease and had
high risk HPV anogenital warts. Pap smears showed low-grade squamous
intraepithelial lesion, guided biopsies identified chronic cervicitis, vulvar,
vaginal, anal and/or cervix intraepithelial neoplasia. All of them were under
corticosteroids and immunosuppressive drugs. The visible genital warts lesions
were eradicated. DISCUSSION: Our patients requires rigorous gynecologic follow-up
due to the severe anogenital dysplasia. HPV vaccine should be indicated in all C
SLE prior to sexual activity.
PMID- 25111419
TI - Reactive arthritis mimicking inflammatory bowel disease arthritis: a challenging
diagnosis.
AB - Reactive arthritis comprises a subgroup of infection-associated arthritis which
occurs after genitourinary or gastrointestinal tract infection in genetically
susceptible hosts. Studies have proposed Salmonella, Shigella or Yersinia
infection as the microorganisms responsible for the post-dysenteric form. The
human leukocyte antigen (HLA)-B27 is a well recognised best-known predisposing
factor. We report a case of HLA-B27-associated reactive arthritis after
Salmonella goldcoast enteritis, mimicking inflammatory bowel disease arthritis.
PMID- 25111420
TI - On the design and analysis of clinical trials with correlated outcomes.
AB - The convention in clinical trials is to regard outcomes as independently
distributed, possibly conditional on covariates, but in some situations they may
be correlated. For example, in infectious diseases, correlation may be induced if
participants have contact with a common infectious source, or share hygienic tips
that prevent infection. This paper discusses the design and analysis of
randomized clinical trials that allow arbitrary correlation among all randomized
participants. This perspective generalizes the traditional perspective of strata,
where patients are exchangeable within strata, and independent across strata. For
theoretical work, we focus on the test of no treatment effect MU(1)-MU(0)=0 when
the n dimensional vector of outcomes follows a Gaussian distribution with known n
* n covariance matrix Sigma, where the half randomized to treatment (placebo)
have mean response MU(1)(MU(0)). We show how the new test corresponds to familiar
tests in simple situations for independent, exchangeable, paired, and clustered
data. We also discuss the design of trials where Sigma is known before or during
randomization of patients and evaluate randomization schemes based on such
knowledge. We provide two complex examples to illustrate the method, one for a
study of 23 family clusters with cardiomyopathy, and the other where the malaria
attack rates vary within households and clusters of households in a Malian
village.
PMID- 25111421
TI - Correlation between inflammatory markers and insulin resistance in pregnancy.
AB - Gestational diabetes mellitus (GDM) is associated with an increased risk of
postpartum type 2 diabetes mellitus and cardiovascular risk factors, such as
obesity, hypertension, dyslipidaemia and systemic inflammation. We aimed to
evaluate further lipid profile and inflammatory status assessed by high sensitive
C-reactive protein (hsCRP) and TNF-alpha in GDM. Based on oral glucose tolerance
testing, participants were stratified into three groups: normal 50 g glucose
challenge test (GCT), normal 100 g glucose tolerance test (NOGTT) (control group)
(n = 40); abnormal GCT NOGTT (glucose intolerance) (n = 37); and GDM (n = 39),
defined by Carpenter and Coustan. The three groups did not demonstrate
significantly different hsCRP levels (p = 0.4180) and lipid profile parameters,
such as total cholesterol (p = 0.4210) and LDL-cholesterol (p = 0.4440) levels.
Triglycerides (p = 0.0150) and atherogenic index of the plasma levels (p =
0.0280) were slightly higher in the GDM group. But, TNF-alpha levels increased
significantly in the GDM (p < 0.0001) and in glucose intolerance (p = 0.0062)
groups as compared with the control group. Among the metabolic syndrome
components, insulin resistance was apparently associated with TNF-alpha, whereas
dyslipidaemia was slightly associated with hsCRP because of the effects of
maternal age on lipid markers. These findings suggest that TNF-alpha has a
stronger correlation with pregnancy-associated insulin resistance than hsCRP at
24 to 28 weeks' gestation.
PMID- 25111422
TI - My friend and mentor: Robert A. Jahrsdoerfer, M.D.
PMID- 25111423
TI - Tympanic membrane manipulation to treat symptoms of patulous eustachian tube.
AB - OBJECTIVE: Patulous eustachian tube (PET) can have a significant negative impact
on a patient's quality of life. Previous work has demonstrated that temporarily
mass loading and stiffening the tympanic membrane significantly reduces these
symptoms. This study examined KTP laser myringoplasty (LM) and cartilage
tympanoplasty (CT) as a means to manipulate the tympanic membrane to alleviate
PET symptoms. STUDY DESIGN: Retrospective case review. SETTING: Academic tertiary
care referral hospital. PATIENTS: Patients (n = 20) were identified from the
senior authors' (M.B.) specialty eustachian tube disorders clinic. Patients met
previously established diagnostic criteria for PET. All patients had a clinically
apparent flaccid segment of the eardrum and had symptom improvement after simple
mass loading of their eardrum in the clinic. INTERVENTIONS: Patients in this
study received either KTP LM (10 patients, 15 ears) or CT (10 patients, 11 ears)
to treat their flaccid eardrum segment in an attempt to alleviate PET symptoms.
MAIN OUTCOME MEASURES: Preoperative and postoperative questionnaire scores and
tympanometry measurements were compared. RESULTS: Patients undergoing CT for PET
had a significant reduction in their symptoms of autophony (p <= 0.001),
conducted breath sounds (p = 0.001), and aural fullness (p = 0.009). KTP LM did
not significantly reduce symptoms. CONCLUSION: Cartilage tympanoplasty provides a
safe and accessible surgical option for the treatment of PET and significantly
reduces the symptoms of autophony, conducted breath sounds, and aural fullness.
Further studies are needed to investigate whether addressing PET symptoms
simultaneously from both the tympanic membrane and the eustachian tube orifice
can improve patient symptoms even further.
PMID- 25111425
TI - Plasmon resonance-enhanced circularly polarized luminescence of self-assembled
meso-tetrakis(4-sulfonatophenyl)porphyrin-surfactant complexes in interaction
with Ag nanoparticles.
AB - The chiroptical properties of an anionic meso-tetrakis(4
sulfonatophenyl)porphyrin (TPPS) complexed with cationic surfactants were
enhanced by interaction with silver nanoparticles (AgNPs) in acidic solution.
Improvement in chiroptical properties was revealed by circular dichroism (CD) and
circularly polarized luminescence (CPL), with |gabs| and |glum| values reaching
0.05 and 0.001 at 303 K, respectively.
PMID- 25111424
TI - Scleral cross-linking using riboflavin and ultraviolet-a radiation for prevention
of progressive myopia in a rabbit model.
AB - Our study demonstrates the effect of scleral cross-linking using riboflavin and
ultraviolet-A radiation on the development of axial myopia in a rabbit model.
Axial length of the eyeball was measured by A-scan ultrasound in 22 New Zealand
white rabbits aged 13 days. The right eyes then underwent 360-degree conjunctival
peritomy with (experimental group, n = 11) or without (control group, n = 11)
scleral cross-linking, followed by tarsorrhaphy. The left eyes served as a
control eye. In the experimental group, the right eyeballs were divided into
quadrants, and every quadrant had either 2 (n = 8) or 6 (n = 3) scleral
irradiation zones, each with an area of 0.2 cm2 and radius of 4 mm. Cross-linking
was performed by dropping 0.1% dextran-free riboflavin-5-phosphate onto the
irradiation zones at 20 s before ultraviolet-A irradiation and every 20 s during
the 200-s irradiation time. UVA radiation (370 nm) was applied perpendicular to
the sclera at 57 mW/cm2 (total UVA light dose, 57 J/cm2). Tarsorrhaphies were
removed on day 55, followed by repeated axial-length measurement. In the control
group, mean axial length in the right eyes increased from 10.50 +/- 0.67 mm at
baseline to 15.69 +/- 0.39 mm 55 days later, for a mean change of 5.19 +/- 0.85
mm. In the experimental group, corresponding values were 10.68 +/- 0.74 mm and
14.29 +/- 0.3 mm, for a mean change of 3.61 +/- 0.76 mm. The between-group
difference in the change in mean axial length was statistically significant (p <
0.001, Mann-Whitney nonparametric test). The present manuscript demonstrates that
scleral cross-linking with riboflavin and ultraviolet-A radiation effectively
prevents occlusion-induced axial elongation in a rabbit model.
PMID- 25111426
TI - Somatic aberrations of mismatch repair genes as a cause of microsatellite
unstable cancers.
AB - Lynch syndrome (LS) is caused by germline mutations in mismatch repair (MMR)
genes, resulting in microsatellite-unstable tumours. Approximately 35% of
suspected LS (sLS) patients test negative for germline MMR gene mutations,
hampering conclusive LS diagnosis. The aim of this study was to investigate
somatic MMR gene aberrations in microsatellite-unstable colorectal and
endometrial cancers of sLS patients negative for germline MMR gene mutations.
Suspected LS cases were selected from a retrospective Clinical Genetics
Department diagnostic cohort and from a prospective multicentre population-based
study on LS in The Netherlands. In total, microsatellite-unstable tumours of 40
sLS patients (male/female 20/20, median age 57 years) were screened for somatic
MMR gene mutations by next-generation sequencing. In addition, loss of
heterozygosity (LOH) of the affected MMR genes in these tumours as well as in 68
LS-associated tumours and 27 microsatellite-unstable tumours with MLH1 promoter
hypermethylation was studied. Of the sLS cases, 5/40 (13%) tumours had two
pathogenic somatic mutations and 16/40 (40%) tumours had a (likely) pathogenic
mutation and LOH. Overall, LOH of the affected MMR gene locus was observed in
24/39 (62%) tumours with informative LOH markers. Of the LS cases and the tumours
with MLH1 promoter hypermethylation, 39/61 (64%) and 2/21 (10%) tumours,
respectively, demonstrated LOH. Half of microsatellite-unstable tumours of sLS
patients without germline MMR gene mutations had two (likely) deleterious somatic
MMR gene aberrations, indicating their sporadic origin. Therefore, we advocate
adding somatic mutation and LOH analysis of the MMR genes to the molecular
diagnostic workflow of LS.
PMID- 25111427
TI - Effect of small molecule vasopressin V1a and V2 receptor antagonists on brain
edema formation and secondary brain damage following traumatic brain injury in
mice.
AB - The attenuation of brain edema is a major therapeutic target after traumatic
brain injury (TBI). Vasopressin (AVP) is well known to play a major role in the
regulation of brain water content and vasoendothelial functions and to be
involved in brain edema formation. Therefore, the aim of the current study was to
analyze the antiedematous efficacy of a clinically relevant, nonpeptidic AVP V1a
and V2 receptor antagonists. C57Bl6 mice were subjected to controlled cortical
impact (CCI) and V1a or V2 receptors were inhibited by using the highly selective
antagonists SR-49059 or SR-121463A either by systemic (intraperitoneal, IP) or
intracerebroventricular (ICV) application. After 24 h, brain edema, intracranial
pressure (ICP), and contusion volume were assessed. Systemically applied AVP
receptor antagonists could not reduce secondary lesion growth. In contrast, ICV
administration of AVP V1a receptor antagonist decreased brain edema formation by
68%, diminished post-traumatic increase of ICP by 46%, and reduced secondary
contusion expansion by 43% 24 h after CCI. The ICV inhibition of V2 receptors
resulted in significant reduction of post-traumatic brain edema by 41% 24 h after
CCI, but failed to show further influence on ICP and lesion growth. Hence,
centrally applied vasopressin V1a receptor antagonists may be used to reduce
brain edema formation after TBI.
PMID- 25111429
TI - In-session processes of brief motivational interventions in two trials with
mandated college students.
AB - OBJECTIVE: Each year, thousands of college students receive mandated intervention
as a sanction for alcohol use or alcohol-related behavior. For these mandated
students, brief motivational interventions (BMIs) are currently the most
efficacious individual intervention. However, little is known about how the
technical (therapist behaviors) and relational (e.g., global ratings of therapist
empathy) components of BMIs influence client language as well as subsequent
change in alcohol use and consequences. METHOD: This study used the Motivational
Interviewing Skills Code (MISC 2.0; Miller, Moyers, Ernst, & Amrhein, 2003) to
code BMI sessions from 2 randomized clinical trials that facilitated significant
reductions in alcohol use (Study 1, n = 91) and alcohol-related consequences
(Study 2, n = 158) in mandated students. RESULTS: There were significant
relationships among therapist behaviors, global scores, and client language both
for and against change, yet there were no links between in-session client
language and subsequent changes in alcohol use or problems. In contrast,
relational aspects of motivational interviewing (MI; global ratings of therapist
MI Spirit and client self-exploration) were most predictive of postsession
alcohol use. Mediation models incorporating both technical and relational
components revealed that higher levels of client self-exploration mediated the
relationship between higher therapist ratings of MI Spirit and reduced drinking
at follow-up. CONCLUSIONS: Findings highlight the importance of considering how
both technical and relational components of MI may influence alcohol use in
mandated college students and also suggest more exact analyses to better
understand this complex relationship.
PMID- 25111431
TI - Testosterone treatment and MMPI-2 improvement in transgender men: a prospective
controlled study.
AB - OBJECTIVE: Most transgender men desire to receive testosterone treatment in order
to masculinize their bodies. In this study, we aimed to investigate the short
term effects of testosterone treatment on psychological functioning in
transgender men. This is the 1st controlled prospective follow-up study to
examine such effects. METHOD: We examined a sample of transgender men (n = 48)
and nontransgender male (n = 53) and female (n = 62) matched controls (mean age =
26.6 years; 74% White). We asked participants to complete the Minnesota
Multiphasic Personality Inventory (2nd ed., or MMPI-2; Butcher, Graham, Tellegen,
Dahlstrom, & Kaemmer, 2001) to assess psychological functioning at baseline and
at the acute posttreatment follow-up (3 months after testosterone initiation).
Regression models tested (a) Gender * Time interaction effects comparing
divergent mean response profiles across measurements by gender identity; (b)
changes in psychological functioning scores for acute postintervention
measurements, adjusting for baseline measures, comparing transgender men with
their matched nontransgender male and female controls and adjusting for baseline
scores; and (c) changes in meeting clinical psychopathological thresholds.
RESULTS: Statistically significant changes in MMPI-2 scale scores were found at 3
month follow-up after initiating testosterone treatment relative to baseline for
transgender men compared with female controls (female template): reductions in
Hypochondria (p < .05), Depression (p < .05), Hysteria (p < .05), and Paranoia (p
< .01); and increases in Masculinity-Femininity scores (p < .01). Gender * Time
interaction effects were found for Hysteria (p < .05) and Paranoia (p < .01)
relative to female controls (female template) and for Hypochondria (p < .05),
Depression (p < .01), Hysteria (p < .01), Psychopathic Deviate (p < .05),
Paranoia (p < .01), Psychasthenia (p < .01), and Schizophrenia (p < .01) compared
with male controls (male template). In addition, the proportion of transgender
men presenting with co-occurring psychopathology significantly decreased from
baseline compared with 3-month follow-up relative to controls (p < .05).
CONCLUSIONS: Findings suggest that testosterone treatment resulted in increased
levels of psychological functioning on multiple domains in transgender men
relative to nontransgender controls. These findings differed in comparisons of
transgender men with female controls using the female template and with male
controls using the male template. No iatrogenic effects of testosterone were
found. These findings suggest a direct positive effect of 3 months of
testosterone treatment on psychological functioning in transgender men.
PMID- 25111430
TI - Individual versus significant-other-enhanced brief motivational intervention for
alcohol in emergency care.
AB - OBJECTIVE: Effects of brief motivational interventions (BMIs) for heavy drinkers
identified by alcohol-related emergency department (ED) visits are mixed. The
successes of including significant others (SOs) in behavioral treatment suggest
that involving SOs in ED-delivered BMI might prove beneficial. This study
investigated the relative efficacy of an SO-enhanced motivational intervention
(SOMI) compared with an individual motivational intervention (IMI) to address
heavy drinking in emergency care settings. METHOD: ED (n = 317) or trauma unit (n
= 89) patients were randomly assigned to receive either an IMI or an SOMI and
were reassessed at 6 and 12 months for alcohol consumption, alcohol-related
consequences, and perceived alcohol-specific SO support. RESULTS: Generalized
estimating equation analyses showed consistent reductions over time for both
alcohol consumption and consequences. At 1-year follow-up, the average reduction
in total drinks consumed per week was greater for patients in the SOMI condition
than the IMI condition. In SOMI, 9.4% more patients moved to within the national
guidelines for weekly drinking than did IMI patients. Frequency of heavy drinking
and negative alcohol consequences showed no differential effects of intervention.
CONCLUSIONS: Emergence of a modest treatment effect at 12 months suggests that SO
involvement in the SOMI condition may have led to more sustained positive
influence on patient drinking than in the IMI condition. Implications and
limitations regarding SO involvement in brief treatment are discussed.
PMID- 25111433
TI - Behavior therapy for depressed breast cancer patients: predictors of treatment
outcome.
AB - OBJECTIVE: Major depressive disorder (MDD) is the most common psychiatric
disorder among breast cancer patients and is associated with substantial
functional impairment. Although several outcome studies have explored the utility
of psychotherapy for breast cancer patients with subsyndromal depression
symptoms, only a few clinical trials have explored the efficacy of behavior
therapy for patients with well-diagnosed MDD. An additional limitation of this
research is that little is known about factors that best predict treatment
outcome. METHOD: In the context of a recent randomized trial of behavior
activation and problem-solving therapy for depressed breast cancer patients (n =
80; Hopko et al., 2011), this study explored predictors of treatment outcome with
selected demographic (age, education, marital status, occupational status),
psychosocial (pretreatment depression and environmental reward, coexistent
anxiety disorders, social support, history of psychotherapy) and cancer-related
variables (cancer stage, duration of cancer diagnosis, and cancer treatment).
RESULTS: Positive treatment outcome as defined by Beck Depression Inventory-II
(Beck et al., 1996) response and remission criteria was associated with being
married, increased social support, not actively undergoing cancer treatment
during psychotherapy, and having a history of psychotherapy. CONCLUSIONS: The
efficacy of behavior therapy for depressed breast cancer patients may depend on
several patient variables. Implications for the provision of behavior therapy for
breast cancer patients are discussed.
PMID- 25111432
TI - Social network influences on initiation and maintenance of reduced drinking among
college students.
AB - OBJECTIVE: To determine whether (a) social networks influence the extent to which
college students initiate and/or maintain reductions in drinking following an
alcohol intervention and (b) students with riskier networks respond better to a
counselor-delivered, vs. a computer-delivered, intervention. METHOD: Mandated
students (N = 316; 63% male) provided their perceptions of peer network members'
drinking statuses (e.g., heavy drinker) and how accepting each friend would be if
the participant reduced his or her drinking. Next, they were randomized to
receive a brief motivational intervention (BMI) or Alcohol Edu for Sanctions
(EDU). In latent growth models controlling for baseline levels on outcomes,
influences of social networks on 2 phases of intervention response were examined:
initiation of reductions in drinks per heaviest week, peak blood alcohol content
(BAC), and consequences at 1 month (model intercepts) and maintenance of
reductions between 1 and 12 months (model slopes). RESULTS: Peer drinking status
predicted initiation of reductions in drinks per heaviest week and peak BAC; peer
acceptability predicted initial reductions in consequences. Peer Acceptability *
Condition interactions were significant or marginal for all outcomes in the
maintenance phase. In networks with higher perceived acceptability of decreasing
use, BMI and EDU exhibited similar growth rates. In less accepting networks,
growth rates were significantly steeper among EDU than BMI participants. For
consumption outcomes, lower perceived peer acceptability predicted steeper rates
of growth in drinking among EDU but not BMI participants. CONCLUSIONS:
Understanding how social networks influence behavior change and how interventions
mitigate their influence is important for optimizing efficacy of alcohol
interventions.
PMID- 25111434
TI - Bis-quaternary gemini surfactants as components of nonviral gene delivery
systems: a comprehensive study from physicochemical properties to membrane
interactions.
AB - Gemini surfactants have been successfully used as components of gene delivery
systems. In the present work, a family of gemini surfactants, represented by the
general structure [CmH2m+1(CH3)2N(+)(CH2)sN(+)(CH3)2CmH2m+1]2Br(-), or simply m-s
m, was used to prepare cationic gene carriers, aiming at their application in
transfection studies. An extensive characterization of the gemini surfactant
based complexes, produced with and without the helper lipids cholesterol and
DOPE, was carried out in order to correlate their physico-chemical properties
with transfection efficiency. The most efficient complexes were those containing
helper lipids, which, combining amphiphiles with propensity to form structures
with different intrinsic curvatures, displayed a morphologically labile
architecture, putatively implicated in the efficient DNA release upon complex
interaction with membranes. While complexes lacking helper lipids were
translocated directly across the lipid bilayer, complexes containing helper
lipids were taken up by cells also by macropinocytosis. This study contributes to
shed light on the relationship between important physico-chemical properties of
surfactant-based DNA vectors and their efficiency to promote gene transfer, which
may represent a step forward to the rational design of gene delivery systems.
PMID- 25111435
TI - Acquired hemophilia: a potentially life-threatening etiology of persistent
bleeding after Mohs micrographic surgery.
PMID- 25111436
TI - Platelet-rich plasma for androgenetic alopecia: a pilot study.
AB - BACKGROUND: Androgenetic alopecia is a common condition, with severe attendant
psychosocial implications, and for which it is difficult to obtain a satisfactory
degree of clinical improvement. OBJECTIVE: To explore the possible clinical
benefit of injecting platelet-derived growth factors into the scalp of patients
using a specific autologous blood concentrate. MATERIALS AND METHODS: Two
injections of a leukocyte platelet-rich plasma (L-PRP) with the addition of
concentrated plasmatic proteins were administered at baseline and after 3 months
(single spin at baseline and double-spin centrifugation at 3 months).
Macrophotographs were taken at baseline and after 6 months, and 2 independent
evaluators rated them using Jaeschke rating of clinical change. RESULTS: Sixty
four consecutive patients were enrolled. Some improvement was seen in all
patients by 1 evaluator and in 62 by the other. The mean change in clinical
rating was 3.2 (95% confidence interval [CI], 2.9-3.5) and 3.9 (95% CI, 3.5-4.3),
and the proportion of patients reaching a clinically important difference was
40.6% and 54.7%, according to the 2 evaluators, respectively. CONCLUSION: Our
pilot study may provide preliminary evidence that this treatment may induce some
degree of clinical advantage for male- and female-pattern baldness. This may
warrant the design of randomized controlled clinical trials to formally test this
procedure.
PMID- 25111437
TI - Fat reduction in the inner thigh using a prototype cryolipolysis applicator.
AB - BACKGROUND: Previous clinical studies have investigated cryolipolysis for
noninvasive reduction of fat in abdomens, outer thighs, flanks, and backs. This
study investigated feasibility of cryolipolysis for inner thigh treatment.
OBJECTIVE: This pilot study evaluated a cryolipolysis flat cup vacuum applicator
for treatment of inner thigh fat. METHODS: A prototype vacuum applicator was used
to treat n = 11 subjects in a single-side inner thigh study. Cryolipolysis
treatment was delivered to the larger thigh while the contralateral thigh served
as a control. Follow-ups were conducted at 8 and 16 weeks. Equalization
treatments were subsequently delivered to the contralateral thigh. Safety was
assessed by monitoring side effects and adverse events. Efficacy was evaluated by
ultrasound imaging, clinical photography, and patient surveys. RESULTS: Side
effects were typical and resolved spontaneously. Efficacy was demonstrated with
ultrasound measurements showing 83% of subjects attained some level of fat layer
reduction. Normalized mean reduction in fat layer thickness was 20%,
corresponding to 3.3 mm. Patient surveys revealed 91% were satisfied and 82% felt
inner thigh cryolipolysis was comfortable. Clinical photographs revealed visible
reduction in inner thigh contour after treatment. CONCLUSION: This study
demonstrates feasibility of safe and efficacious cryolipolysis treatment to the
inner thigh.
PMID- 25111438
TI - A comparison of the scar prevention effect between carbon dioxide fractional
laser and pulsed dye laser in surgical scars.
AB - BACKGROUND: The use of ablative lasers based on the fractional approach is a
novel strategy for the treatment of postoperative and acne scars in addition to
wrinkles. OBJECTIVE: To evaluate and compare the efficacy of carbon dioxide
ablative fractional laser (AFL) and the pulsed dye laser (PDL) for the
improvement of surgical scars. MATERIALS AND METHODS: Fourteen Korean patients
with surgical scars were enrolled for this study. Half of each scar was treated
with a 10,600-nm AFL and the contralateral half with the 595-nm PDL. For early
intervention of the postoperative scar, the laser treatments were begun after 2
weeks from the Mohs micrographic surgery. RESULTS: Both PDL and AFL produced
statistically significant improvements. However, comparatively, there was no
statistical difference between them. In each variable, AFL was more effective
than PDL in the improvement of pliability and thickness. In contrast, PDL was
superior to AFL in the improvement of vascularity and pigmentation. CONCLUSION:
Pulsed dye laser and AFL treatments for surgical scar provide significant
improvement. Pulsed dye laser was more effective in color of scar compared with
AFL, which showed marked improvement in the contour of scar. Overall improvement
was not statistically different in the Vancouver Scar Scale.
PMID- 25111440
TI - Sulfur copolymer nanowires with enhanced visible-light photoresponse.
AB - Sulfur copolymer nanowires have been reported for the first time as highly stable
visible-light-active photocatalysts for photoelectrochemical water splitting
depending on their size and sulfur content. The as-prepared sulfur copolymer
nanowires can serve as a sulfur source and templates to create metal
sulfide/copolymer heterocatalysts.
PMID- 25111441
TI - One-pot method for synthesizing spherical-like metal sulfide-reduced graphene
oxide composite powders with superior electrochemical properties for lithium-ion
batteries.
AB - A facile, one-pot method for synthesizing spherical-like metal sulfide-reduced
graphene oxide (RGO) composite powders by spray pyrolysis is reported. The direct
sulfidation of ZnO nanocrystals decorated on spherical-like RGO powders resulted
in ZnS-RGO composite powders. ZnS nanocrystals with a size below 20 nm were
uniformly dispersed on spherical-like RGO balls. The discharge capacities of the
ZnS-RGO, ZnO-RGO, bare ZnS, and bare ZnO powders at a current density of 1000 mA
g(-1) after 300 cycles were 628, 476, 230, and 168 mA h g(-1), respectively, and
the corresponding capacity retentions measured after the first cycles were 93,
70, 40, and 21 %, respectively. The discharge capacity of the ZnS-RGO composite
powders at a high current density of 4000 mA g(-1) after 700 cycles was 437 mA h
g(-1). The structural stability of the highly conductive ZnS-RGO composite
powders with ultrafine crystals during cycling resulted in excellent
electrochemical properties.
PMID- 25111439
TI - Pyrano-isochromanones as IL-6 inhibitors: synthesis, in vitro and in vivo
antiarthritic activity.
AB - Bergenin (1), a unique fused C-glycoside isolated from Bergenia species,
possesses interesting anti-inflammatory and antipain activities. To study SAR of
this scaffold, first-generation derivatives were synthesized and evaluated for
inhibition of lymphocyte proliferation and production of pro-inflammatory
cytokines. The C-7 substituted derivatives showed inhibition of IL-6 as well as
TNF-alpha production. Bergenin and its most potent IL-6 inhibitor derivatives 4e
and 4f were then investigated in a panel of in vitro and in vivo
inflammation/arthritis models. These compounds significantly decreased the
expression of NF-kB and IKK-beta in THP-1 cells. In in vivo study in BALB/c mice,
a dose-dependent inhibition of SRBC-induced cytokines, reduction in humoral/cell
mediated immunity, and antibody titer was observed. The CIA study in DBA/1J mice
indicated that compounds led to reduction in swelling of paws, cytokine levels,
and anticollagen IgG1/IgG2a levels. The significant in vivo immunosuppressive
efficacy of pyrano-isochromanones demonstrates the promise of this scaffold for
development of next-generation antiarthritic drugs.
PMID- 25111443
TI - Iridium-catalyzed enantioselective allyl-allylsilane cross-coupling.
AB - An enantioselective allyl-allylsilane cross-coupling involving racemic branched
allylic alcohols and allylsilanes is reported. An iridium-(P,olefin)
phosphoramidite complex enables the transformation with high regio- and
stereoselectivity under operationally simple conditions. The utility of the
coupling is demonstrated in a concise catalytic, enantioselective synthesis of a
pyrethroid insecticide protrifenbute.
PMID- 25111442
TI - An automated three-dimensional detection and segmentation method for touching
cells by integrating concave points clustering and random walker algorithm.
AB - Characterizing cytoarchitecture is crucial for understanding brain functions and
neural diseases. In neuroanatomy, it is an important task to accurately extract
cell populations' centroids and contours. Recent advances have permitted imaging
at single cell resolution for an entire mouse brain using the Nissl staining
method. However, it is difficult to precisely segment numerous cells, especially
those cells touching each other. As presented herein, we have developed an
automated three-dimensional detection and segmentation method applied to the
Nissl staining data, with the following two key steps: 1) concave points
clustering to determine the seed points of touching cells; and 2) random walker
segmentation to obtain cell contours. Also, we have evaluated the performance of
our proposed method with several mouse brain datasets, which were captured with
the micro-optical sectioning tomography imaging system, and the datasets include
closely touching cells. Comparing with traditional detection and segmentation
methods, our approach shows promising detection accuracy and high robustness.
PMID- 25111446
TI - Electroconvulsive therapy in obsessive-compulsive disorder: a chart review and
evaluation of its potential therapeutic effects.
AB - In a chart review of patients with obsessive-compulsive disorder (OCD) attending
a university clinic, ECT was prescribed for five subjects (1.2%), only because of
severe intervening manic (N=1) or depressive episodes (N=4). Although affective
symptoms improved in four of the five patients, OCD symptoms remained unchanged
(N=3) or transiently worsened (N=2).
PMID- 25111444
TI - Evaluation of staging and early response to chemotherapy with whole-body
diffusion-weighted MRI in malignant lymphoma patients: A comparison with FDG
PET/CT.
AB - BACKGROUND: To examine the utility of diffusion-weighted MRI (DW-MRI) for staging
and early response to chemotherapy assessment in lymphoma patients as compared
with fluorodeoxyglucose positron emission tomography/computed tomography (FDG
PET/CT). METHODS: Twenty-eight patients with histologically confirmed malignant
lymphoma underwent both MRI and FDG-PET/CT before (pretreatment) and after two
courses of chemotherapy (mid-treatment). Staging with MRI (DW-MRI alone and with
T2-weighted images) and FDG-PET was compared visually, and the concordance rate
(kappa value, kappa) was calculated. To evaluate early response to chemotherapy,
patients were divided into two groups, lesion-positive (LP) and lesion-negative
(LN), based on a proposed original criterion. Progression-free survival (PFS) was
compared between the groups using the Kaplan-Meier method. RESULTS: The stage
diagnosed with DW-MRI alone and with FDG-PET/CT was concordant in 22 patients
(kappa = 0.71; P < 0.05), and by adding T2-weighted images, the number of
concordant patients increased to 26 (kappa = 0.90; P < 0.05). On mid-treatment
imaging, 19 patients were diagnosed as LN from both modalities. PFS differed
significantly between LP and LN on both DW-MRI (P = 0.0013) and FDG-PET/CT (P =
0.037). CONCLUSION: DW-MRI is a promising tool for staging and evaluation of
early response to chemotherapy in patients with lymphoma.
PMID- 25111445
TI - Mechanical characterization of a bifunctional Tetronic hydrogel adhesive for soft
tissues.
AB - Although a number of tissue adhesives and sealants for surgical use are currently
available, attaining a useful balance in high strength, high compliance, and low
swelling has proven difficult. Recent studies have demonstrated that a four-arm
poly(propylene oxide)-poly(ethylene oxide) block copolymer, Tetronic, can be
chemically modified to form a hydrogel tissue adhesive (Cho et al., Acta Biomater
2012;8:2223-2232; Barrett et al., Adv Health Mater 2012;1-11; Balakrishnan,
Evaluating mechanical performance of hydrogel-based adhesives for soft tissue
applications. Clemson University, All Theses, Paper 1574: Tiger Prints; 2013).
Building on the success of these studies, this study explored bifunctionalization
of Tetronic with acrylates for chemical crosslinking of the hydrogel and N
hydroxysuccinimide (NHS) for reaction with tissue amines. The adhesive bond
strengths of various uni and bifunctional Tetronic blends (T1107 ACR: T1107
ACR/NHS) determined by lap shear testing ranged between 8 and 74 kPa, with the
75:25 (T1107 ACR: T1107 ACR/NHS) blend displaying the highest value. These
results indicated that addition of NHS led to improvement of tissue bond strength
over acrylation alone. Furthermore, ex vivo pressure tests using the rat bladder
demonstrated that the bifunctional Tetronic adhesive exhibited high compliance
and maintained pressures under hundreds of filling and emptying cycles. Together,
the results of this study provided evidence that the bifunctional Tetronic
adhesive with a proper blend ratio may be used to achieve an accurate balance in
bulk and tissue bond strengths, as well as the compliance and durability for soft
tissue such as the bladder.
PMID- 25111447
TI - [Validation of the German short version of the Murray Secretion Rating Scale].
AB - OBJECTIVE: Accumulation of secretions in hypopharynx, aditus vestibule, and
trachea is often found in cases of severe dysphagia and is considered a cardinal
trait of high clinical and therapeutic importance. For the graduation of the
severity level of accumulated secretions, a short version of the 4-point Murray
secretion scale is available, which is also integrated into the protocol of the
fiberoptic endoscopic evaluation of swallowing (FEES) according to the Langmore
standard. This study aimed at the validation of the German translation of this
short version in order to facilitate a uniform, standardized evaluation of the
accumulation of secretions in dysphagic patients in the German language area.
MATERIAL AND METHODS: For the examination of reliability and validity, a
reference standard was defined by 2 dysphagia experts on the basis of 40 video
files of the FEES examination, 10 videos for each of the severity grades.
Afterwards, these videos were rated independently by 4 raters and re-rated in a
new randomized order 2 weeks later. RESULTS: Both the intra-rater reliability
(tau>0,830***) and the inter-rater reliability (Kendalls W>0,890***) were highly
significant and can be considered good. The same is valid for the correlation of
ratings with the reference standard (tau=0,969***). CONCLUSIONS: The German
translation of the short version of the 4-point Murray secretion scale is
recommendable as a reliable and valid instrument for the graduation of the
cardinal trait of oropharyngeal dysphagia and also as an evidence-based
instrument for standardized use in the German language area.
PMID- 25111448
TI - [Inpatient vs. outpatient costs analysis of septumplasty in Germany].
AB - The septumplasty is realized inpatient and outpatient in different countries.
Caused by the pressure of reduction of expenses there is the question of the
economic benefit if done outpatient in Germany. A comparison of the inpatient and
outpatient gratification will be done. There is a yearly potential of cost
reduction of 180 million euro, if the operation would be done as an outpatient
procedure. From the hospital view actual there is no economical recommendation
doing an outpatient septumplasty caused by the poor outpatient remuneration.
That's why an adjustment of the outpatient remuneration should be done. Actual
there is no medical or economical recommendation doing the septumplasty as an
outpatient procedere.
PMID- 25111450
TI - Catalytic purification of directly written nanostructured Pt microelectrodes.
AB - In the majority of cases, nanostructures prepared by focused electron beam
induced deposition employing an organometallic precursor contain predominantly
carbon-based ligand dissociation products. This is unfortunate with regard to
using this high-resolution direct-write approach for the preparation of
nanostructures for various fields, such as mesoscopic physics, micromagnetism,
metaoptical phenomena in the visible spectral range, or others. Following early
attempts of postprocessing Pt-based structures prepared by focused electron beam
induced deposition at several hundred degrees Celsius in a reactive gas
atmosphere, recent work has focused on developing in situ purification processes
by using a stationary O2 flux in combination with electron irradiation to oxidize
the carbonaceous component of the deposits. Here we show that this purification
process is driven by the catalytic activity of Pt and in fact does not rely on
the parallel electron irradiation process to function, if the O2 exposure is done
in a pulsed fashion. We suggest a multistep cleaning mechanism which results in
pure, nanoporous Pt. By suitably chosen beam parameters, high-resolution Pt dot
and line structures with dimensions below 10 nm can thus be conveniently
obtained. In temperature-dependent resistance measurements, we find the typical
metallic behavior of Pt. In low-temperature magnetoresistance measurements, we
see clear evidence for weak antilocalization effects and deduce a dephasing
length of 234 nm at 1.2 K. We consider this to be a promising starting point for
developing this approach into a versatile preparation technique for Pt-based
mesoscopic structures, in particular since the purification process can be run in
parallel on different deposits. We furthermore anticipate that our results will
spur further research on purification approaches for nanostructures prepared by
focused electron beam induced deposition containing a catalytically active metal
species such as Pd-, Fe-, or Co-based deposits.
PMID- 25111449
TI - The relative validity and repeatability of an FFQ for estimating intake of zinc
and its absorption modifiers in young and older Saudi adults.
AB - OBJECTIVE: To assess the relative validity and repeatability of a sixty-four-item
FFQ for estimating dietary intake of Zn and its absorption modifiers in Saudi
adults. In addition, we used the FFQ to investigate the effect of age and gender
on these intakes. DESIGN: To assess validity, all participants completed the FFQ
(FFQ1) and a 3 d food record. After 1 month, the FFQ was administered for a
second time (FFQ2) to assess repeatability. SETTING: Jeddah, Saudi Arabia.
SUBJECTS: One hundred males and females aged 20-30 years and 60-70 years
participated. RESULTS: Mean intakes of Zn and protein from FFQ1 were
significantly higher than those from the food record while there were no
detectable differences between tools for measurement of phytic acid intake.
Estimated intakes of Zn, protein and phytate by both approaches were strongly
correlated (P<0.001). Bland-Altman analysis showed for protein that the
difference in intake as measured by the two methods was similar across the range
of intakes while for Zn and phytic acid, the difference increased with increasing
mean intake. Zn and protein intakes from FFQ1 and FFQ2 were highly correlated
(r>0.68, P<0.001) but were significantly lower at the second measurement (FFQ2).
Older adults consumed less Zn and protein compared with young adults. Intakes of
all dietary components were lower in females than in males. CONCLUSIONS: The FFQ
developed and tested in the current study demonstrated reasonable relative
validity and high repeatability and was capable of detecting differences in
intakes between age and gender groups.
PMID- 25111455
TI - Impact of sympathetic dysfunction in the etiology of overactive bladder in women:
A preliminary study.
AB - AIMS: We investigated the effects of autonomic sympathetic dysfunction in the
etiology of overactive bladder (OAB) in women, by assessing the sympathetic skin
response (SSR). METHODS: In total, 40 women with OAB and 15 volunteers were
enrolled. Group 1 (n = 20) consisted of patients who benefitted from oral
anticholinergics, Group 2 (n = 20) consisted of patients who were refractory to
oral anticholinergics, and the volunteers (n = 15) were the control group. All
patients were asked to complete OAB-SF questionnaires. The absence of SSR was
accepted as significant. Detailed physical examinations including neurological
examinations were performed. All patients underwent SSR tests on the skin of the
hands, feet, and genital area in our neurology department using electromyography,
and SSR responses were recorded. Statistical significance was accepted at P <
0.05. RESULTS: The mean age was 47.2 +/- 12.4 years. In total, 55 women were
evaluated (20 in Group 1, 20 in Group 2, and 15 in the control group). Mean OAB
scores were similar between groups 1 and 2, although urgency was significantly
higher in Group 2 than 1. The absence of SSR was significantly higher in Group 2
than 1 (P = 0.01). Impaired SSR was observed more commonly in Group 2 than 1. All
controls had normal SSRs. CONCLUSIONS: Regional dysfunction in the autonomic
nervous system may be part of OAB's etiology. SSR may be a candidate test for
determining early OAB, and may also be useful for predicting antimuscarinic
refractory patients.
PMID- 25111456
TI - Power spectral changes of the superimposed M wave during isometric voluntary
contractions of increasing strength.
AB - INTRODUCTION: We examined the power spectral changes of the compound muscle
action potential (M wave) evoked during isometric contractions of increasing
strength. METHODS: Surface electromyography (sEMG) of the vastus lateralis and
medialis was recorded from 20 volunteers who performed 4-s step-wise isometric
contractions of different intensities. A maximal M wave was elicited by a single
stimulus to the femoral nerve and superimposed on the voluntary contractions. The
spectral characteristics (Fmean and Fmedian) of sEMG and M-wave signals were
calculated. RESULTS: M-wave spectral indicators increased systematically with
contraction intensity up to 60% MVC and then leveled off at higher forces. Over
the 10-60% MVC range, the increase in spectral indicators was 3 times higher for
M waves (36%) than for sEMG (12%). CONCLUSIONS: The consistent increase in M-wave
spectral characteristics with force is due to the fact that the number of motor
units recruited by the superimposed supramaximal stimulus is approximately
stable.
PMID- 25111457
TI - Where are we in the modelling of traumatic brain injury? Models complicated by
secondary brain insults.
AB - BACKGROUND: Traumatic brain injury (TBI) contributes to a substantial number of
deaths and cases of disability. Despite well-established experimental models and
years of carefully conducted research, a clinical therapeutic breakthrough in TBI
has lagged. This may be due, in part, to the discrepancies between commonly used
experimental models and clinical scenarios. METHOD: Secondary insults, such as
hypotension and hypoxemia, have been well demonstrated as powerful determinants
of outcomes from TBI. Despite the frequency of secondary insults in patients with
TBI, they are rarely incorporated into most existing models of TBI. This review
focuses on the combined injury models, especially coupled with systemic secondary
insults, and aims to provide a new view to guiding future research endeavors in
this field. RESULTS: A growing number of experimental models of TBI complicated
by certain secondary insult have been gradually introduced and characterized.
Correspondingly, the pathophysiological changes following combined injuries and
the interactive effects of primary injury with secondary insults can be studied
more in-depth. CONCLUSION: A more complete understanding of the interactions
between the injured brain and secondary insults represents a potentially fruitful
avenue that may increase the likelihood of developing effective therapies.
Experimental models of TBI should not only attempt to model the focal or diffuse
changes resulting from external forces, but also integrate, when appropriate,
secondary insults reminiscent of human situations.
PMID- 25111458
TI - Effects of acute exposure to the non-steroidal anti-inflammatory drug ibuprofen
on the developing North American Bullfrog (Rana catesbeiana) tadpole.
AB - A variety of pharmaceutical chemicals can represent constituents of municipal
effluent outflows that are dispersed into aquatic receiving environments
worldwide. Increasingly, there is concern as to the potential of such bioactive
substances to interact with wildlife species at sensitive life stages and affect
their biology. Using a combination of DNA microarray, quantitative real-time
polymerase chain reaction, and quantitative nuclease protection assays, we
assessed the ability of sub-lethal and environmentally relevant concentrations of
ibuprofen (IBF), a non-steroidal anti-inflammatory agent and prevalent
environmental contaminant, to function as a disruptor of endocrine-mediated post
embryonic development of the frog. While the LC50 of IBF for pre-metamorphic Rana
catesbeiana tadpoles is 41.5 mg/L (95% confidence interval: 32.3-53.5 mg/L),
exposure to concentrations in the ppb range elicited molecular responses both in
vivo and in organ culture. A nominal concentration of 15 MUg/L IBF (actual = 13.7
MUg/L) altered the abundance of 26 mRNA transcripts within the liver of exposed
pre-metamorphic R. catesbeiana tadpoles within 6 d. IBF-treated animals
demonstrated subsequent disruption of thyroid hormone-mediated reprogramming in
the liver transcriptome affecting constituents of several metabolic,
developmental, and signaling pathways. Cultured tadpole tail fin treated with IBF
for 48 h also demonstrated altered mRNA levels at drug concentrations as low as
1.5 MUg/L. These observations raise the possibility that IBF may alter the post
embryonic development of anuran species in freshwater environs, where IBF is a
persistent or seasonal pollutant.
PMID- 25111459
TI - Folate testing: time to retire your VCR.
PMID- 25111460
TI - Oxidized low density lipoprotein increases acetylcholinesterase activity
correlating with reactive oxygen species production.
AB - Hyperlipidemia, low density lipoproteins (LDL) and their oxidized forms, and
oxidative stress are suspected to be a key combination in the onset of AD and
acetylcholinesterase (AChE) plays a part in this pathology. The present study
aimed to link these parameters using differentiated SH-SY5Y human neuroblastoma
cells in culture. Both mildly and fully oxidized human LDL (mox- and fox-LDL),
but not native (non-oxidized) LDL were cytotoxic in dose- and time-dependent
patterns and this was accompanied by an increased production of intracellular
reactive oxygen species (ROS). Oxidized LDL (10-200 MUg/mL) augmented AChE
activity after 4 and 24h treatments, respectively while the native LDL was
without effect. The increased AChE with oxidized LDLs was accompanied by a
proportionate increase in intracellular ROS formation (R=0.904). These findings
support the notion that oxidized LDLs are cytotoxic and that their action on AChE
may reduce central cholinergic transmission in AD and affirm AChE as a continued
rational for anticholinesterase therapy but in conjunction with
antioxidant/antihyperlipidemic cotreatments.
PMID- 25111461
TI - miR-129-1-3p promote BGC-823 cell proliferation by targeting PDCD2.
AB - MicroRNAs (miRNAs) are the class of small noncoding RNAs, and play an important
role in the regulation of gene expression at the posttranscriptional level. In
this study, we explored the effect of miR-129-1-3p on the growth and cell cycle
of human gastric cancer cell line BGC-823. The miR-129-1-3p mimics or inhibitors
were transfected into the BGC-823 cell line, and the cell cycle and cell growth
was measured by flow cytometry and real-time cell analyzer, respectively. The
possible targets of miR-129-1-3p were analyzed by quantitative real time-PCR (QRT
PCR), Western blotting and Luciferase reporter assay. The results showed that miR
129-1-3p could promote the growth and cell cycle of BGC-823 cells. Although
protein expression of programmed cell death 2 (PDCD2) was not changed with miR
129-1-3p, QRT-PCR showed that expression of PDCD2 mRNA was negatively related to
the miR-129-1-3p. Luciferase reporter assay revealed that PDCD2 is one of the
targets of miR-129-1-3p. Our results indicated that miR-129-1-3p might promote
proliferation of BGC-823 cells by targeting PDCD2.
PMID- 25111462
TI - Impact of several pre-treatments on the extraction of phenolic compounds in
winegrape varieties with different anthocyanin profiles and skin mechanical
properties.
AB - This study was performed to evaluate and compare the effects of different pre
treatments of whole grape berries (freezing with dry ice or in a cold room, steam
blanching with different exposure times, and microwave heating with different
exposure times and microwave power density) on total content of some phenolic
compounds and the composition of individual anthocyanins released into the pulp
during the treatment and those extracted during the maceration step. Two red
winegrape varieties with different proportions of di- and trisubstituted
anthocyanins were used (Nebbiolo and Barbera, respectively). Pulp-extracted
anthocyanins were more significantly influenced by the pre-treatment. The results
highlighted that freezing with dry ice, followed by freezing in a cold room and
steam blanching for 5 min, have a great potential from an industrial point of
view. They facilitated the extraction of anthocyanins in the must prior to
maceration, when compared with the control samples, increasing their total
content (+37.8-83.6%), and modifying the anthocyanin profile through the
enrichment in the most stable compounds (+2.8-6.6% malvidin derivatives) to the
detriment of others more prone to oxidation (-0.8-11.0% cyanidin derivatives). In
Nebbiolo winegrapes, an improved extraction of low- and high-molecular weight
flavanols into the pulp was also observed (+60.4-73.4%). Significant
relationships between the phenolic composition of treated berries and the
corresponding skin mechanical properties were also studied, but they were variety
dependent. Discriminant analysis permitted a correct classification of the
samples according to the variety and pre-treatment.
PMID- 25111463
TI - Breaking immune tolerance by targeting CD25+ regulatory T cells is essential for
the anti-tumor effect of the CTLA-4 blockade in an HLA-DR transgenic mouse model
of prostate cancer.
AB - INTRODUCTION: Recent studies suggest that the cancer immunotherapy based on the
blockade of the CTLA-4-mediated inhibitory pathway is efficacious only in select
populations, predominantly for immunogenic tumors or when delivered in
combination with modalities that can break immunologic tolerance to tumor
antigens. METHODS: We studied the effect of CD25+ cell depletion and CTLA-4
blockade on the growth of Transgenic Mouse Adenocarcinoma of Prostate (TRAMP)-PSA
tumor cells in DR2bxPSA F1 mice. In these mice, immunological tolerance to PSA
was established in a context of the HLA-DRB1*1501(DR2b) allele. RESULTS: In our
model, single administration of anti-CD25 antibody prior to tumor inoculation
significantly increased IFN-gamma production in response to the CD8 T cell
epitope PSA65-73 , and delayed TRAMP-PSA tumor growth compared to mice treated
with isotype control antibodies. In contrast, the anti-tumor effect of the anti
CTLA-4 antibody as a monotherapy was marginal. The combinatory treatment with
anti-CD25/anti-CTLA-4 antibodies significantly enhanced anti-tumor immunity and
caused more profound delay in tumor growth compared to each treatment alone. The
proportion of tumor-free animals was higher in the group that received
combination treatment (21%) compared to other groups (2-7%). The enhanced anti
tumor immunity in response to the CD25 depletion or CTLA-4 blockade was only seen
in the immunogenic TRAMP-PSA tumor model, whereas the effect was completely
absent in mice bearing poorly immunogenic TRAMP-C1 tumors. DISCUSSION: Our data
suggest that breaking immunological tolerance to "self" antigens is essential for
the therapeutic effect of CTLA-4 blockade. Such combinatory treatment may be a
promising approach for prostate cancer immunotherapy.
PMID- 25111464
TI - School climate, family structure, and academic achievement: a study of moderation
effects.
AB - School climate has been lauded for its relationship to a host of desirable
academic, behavioral, and social-emotional outcomes for youth. The present study
tested the hypothesis that school climate counteracts youths' home-school risk by
examining the moderating effects of students' school climate perceptions on the
relationship between family structure (i.e., two-parent, one-parent, foster-care,
and homeless households), and academic performance (i.e., self-reported [grade
point average] GPA). The present sample consisted of 902 California public high
schools, including responses from over 490,000 students in Grades 9 and 11.
Results indicated that, regardless of family structure, students with more
positive school climate perceptions self-reported higher GPAs. Youths with two
parent, one-parent, and homeless family structures displayed stepwise, linear
improvements in self-reported GPA as perceptions of climate improved. Foster-care
students' positive school climate perceptions had a weaker effect on their self
reported GPA compared with students living in other family structures. A unique
curvilinear trend was found for homeless students, as the relationship between
their school climate perceptions and self-reported GPA was stronger at lower
levels. Overall, the moderation effect of positive school climate perceptions on
self-reported GPA was strongest for homeless youth and youth from one-parent
homes, suggesting that school climate has a protective effect for students living
in these family structures. A protective effect was not found for youth in foster
care. Implications for research and practice are discussed.
PMID- 25111465
TI - Efficacy of the Social Skills Improvement System Classwide Intervention Program
(SSIS-CIP) primary version.
AB - A multisite cluster randomized trial was conducted to examine the effects of the
Social Skills Improvement System Classwide Intervention Program (SSIS-CIP;
Elliott & Gresham, 2007) on students' classroom social behavior. The final sample
included 432 students across 38 second grade classrooms. Social skills and
problem behaviors were measured via the SSIS rating scale for all participants,
and direct observations were completed for a subsample of participants within
each classroom. Results indicated that the SSIS-CIP demonstrated positive effects
on teacher ratings of participants' social skills and internalizing behaviors,
with the greatest changes occurring in classrooms with students who exhibited
lower skill proficiency prior to implementation. Statistically significant
differences were not observed between treatment and control participants on
teacher ratings of externalizing problem behaviors or direct observation.
PMID- 25111466
TI - Examination of the change in latent statuses in bullying behaviors across time.
AB - Involvement in bullying and victimization has been mostly studied using cross
sectional data from 1 time point. As such, much of our understanding of bullying
and victimization has not captured the dynamic experiences of youth over time. To
examine the change of latent statuses in bullying and victimization, we applied
latent transition analysis examining self-reported bullying involvement from
1,180 students in 5th through 9th grades across 3 time points. We identified
unobserved heterogeneous subgroups (i.e., latent statuses) and investigated how
students transition between the unobserved subgroups over time. For
victimization, 4 latent statuses were identified: frequent victim (11.23%),
occasional traditional victim (28.86%), occasional cyber and traditional victim
(10.34%), and infrequent victim (49.57%). For bullying behavior, 3 latent
statuses were identified: frequent perpetrator (5.12%), occasional
verbal/relational perpetrator (26.04%), and infrequent perpetrator (68.84%). The
characteristics of the transitions were examined. The multiple-group effects of
gender, grade, and first language learned on transitions across statuses were
also investigated. The infrequent victim and infrequent perpetrator groups were
the most stable, and the frequent victim and frequent perpetrator groups were the
least stable. These findings suggest instability in perpetration and
victimization over time, as well as significant changes, especially during school
transition years. Findings suggest that school-based interventions need to
address the heterogeneity in perpetrator and victim experiences in adolescence.
PMID- 25111467
TI - Psychosocial functioning of bullied youth who adopt versus deny the bully-victim
label.
AB - This study addressed a need for research on the association between adopting or
denying the label of bully victim and students' psychosocial functioning.
Participants were 1,063 students in Grades 5, 7, and 9 in a school district in
the northeastern United States. Students were grouped based on their pattern of
responses to (a) the California Bully Victimization Scale (Felix et al., 2011),
which does not use the term "bully," but includes behavioral items assessing
frequency of peer victimization and whether or not that victimization involved
any perceived power disadvantage, and (b) the Olweus Bully/Victim Questionnaire
(Solberg & Olweus, 2003; Solberg, Olweus, & Endresen, 2007), which queries self
identification as a bully victim. We compared groups using a series of planned
comparisons with ANOVA on self-reported emotional distress and withdrawal,
behavioral reactivity and conduct problems, and prosocial behavior and peer
competence, as measured by the Strengths and Difficulties Questionnaire (Goodman,
1997). Results revealed complexities regarding the experience of bullying. The
perception of a power difference and having been bullied both related to
psychosocial functioning in an interactive way, suggesting that both are
important to query. Moreover, students who labeled themselves as victims of
bullying reported poorer psychosocial functioning than those who had the
experience of being bullied but did not adopt that label.
PMID- 25111468
TI - Identifying emotional and behavioral risk among gifted and nongifted children: A
multi-gate, multi-informant approach.
AB - The purpose of the current investigation was to compare 1,206 gifted and
nongifted elementary students on the identification of emotional and behavioral
risk (EBR) as rated by teachers and parents using a multigate, multi-informant
approach to assessment. The Parent and Teacher Behavioral Assessment System for
Children, Second Edition (BASC-2) and the Behavioral and Emotional Screening
System were used to assess behavioral functioning as rated by teachers and
parents. There were significant differences between the number of gifted and
nongifted children demonstrating emotional and behavioral risk, with parents and
teachers identifying a higher number of boys and nongifted children as at risk.
Among children demonstrating EBR, gifted children demonstrated elevated
internalizing behaviors as rated by parents. Gifted students demonstrated higher
academic performance regardless of risk level, suggesting higher cognitive
abilities may be one of several protective factors that serve to attenuate the
development of other social, emotional, or behavioral concerns. Implications for
practice and future research needs are discussed.
PMID- 25111469
TI - A comparison of measures to screen for social, emotional, and behavioral risk.
AB - The purpose of this study was to examine the relation between teacher-implemented
screening measures used to identify social, emotional, and behavioral risk. To
this end, 5 screening options were evaluated: (a) Direct Behavior Rating - Single
Item Scales (DBR-SIS), (b) Social Skills Improvement System - Performance
Screening Guide (SSiS), (c) Behavioral and Emotional Screening System - Teacher
Form (BESS), (d) Office discipline referrals (ODRs), and (e) School nomination
methods. The sample included 1974 students who were assessed tri-annually by
their teachers (52% female, 93% non-Hispanic, 81% white). Findings indicated that
teacher ratings using standardized rating measures (DBR-SIS, BESS, and SSiS)
resulted in a larger proportion of students identified at-risk than ODRs or
school nomination methods. Further, risk identification varied by screening
option, such that a large percentage of students were inconsistently identified
depending on the measure used. Results further indicated weak to strong
correlations between screening options. The relation between broad behavioral
indicators and mental health screening was also explored by examining
classification accuracy indices. Teacher ratings using DBR-SIS and SSiS correctly
identified between 81% and 91% of the sample as at-risk using the BESS as a
criterion. As less conservative measures of risk, DBR-SIS and SSiS identified
more students as at-risk relative to other options. Results highlight the
importance of considering the aims of the assessment when selecting broad
screening measures to identify students in need of additional support.
PMID- 25111470
TI - Characteristics of the default mode functional connectivity in normal ageing and
Alzheimer's disease using resting state fMRI with a combined approach of entropy
based and graph theoretical measurements.
AB - Cognitive decline in normal ageing and Alzheimer's disease (AD) emerges from
functional disruption in the coordination of large-scale brain systems sustaining
cognition. Integrity of these systems can be examined by correlation methods
based on analysis of resting state functional magnetic resonance imaging (fMRI).
Here we investigate functional connectivity within the default mode network (DMN)
in normal ageing and AD using resting state fMRI. Images from young and elderly
controls, and patients with AD were processed using spatial independent component
analysis to identify the DMN. Functional connectivity was quantified using
integration and indices derived from graph theory. Four DMN sub-systems were
identified: Frontal (medial and superior), parietal (precuneus-posterior
cingulate, lateral parietal), temporal (medial temporal), and hippocampal
(bilateral). There was a decrease in antero-posterior interactions (lower global
efficiency), but increased interactions within the frontal and parietal sub
systems (higher local clustering) in elderly compared to young controls. This
decreased antero-posterior integration was more pronounced in AD patients
compared to elderly controls, particularly in the precuneus-posterior cingulate
region. Conjoint knowledge of integration measures and graph indices in the same
data helps in the interpretation of functional connectivity results, as
comprehension of one measure improves with understanding of the other. The
approach allows for complete characterisation of connectivity changes and could
be applied to other resting state networks and different pathologies.
PMID- 25111471
TI - Optical Coherence Tomography angiography reveals laminar microvascular
hemodynamics in the rat somatosensory cortex during activation.
AB - The BOLD (blood-oxygen-level dependent) fMRI (functional Magnetic Resonance
Imaging) signal is shaped, in part, by changes in red blood cell (RBC) content
and flow across vascular compartments over time. These complex dynamics have been
challenging to characterize directly due to a lack of appropriate imaging
modalities. In this study, making use of infrared light scattering from RBCs,
depth-resolved Optical Coherence Tomography (OCT) angiography was applied to
image laminar functional hyperemia in the rat somatosensory cortex. After
defining and validating depth-specific metrics for changes in RBC content and
speed, laminar hemodynamic responses in microvasculature up to cortical depths of
>1mm were measured during a forepaw stimulus. The results provide a comprehensive
picture of when and where changes in RBC content and speed occur during and
immediately following cortical activation. In summary, the earliest and largest
microvascular RBC content changes occurred in the middle cortical layers, while
post-stimulus undershoots were most prominent superficially. These laminar
variations in positive and negative responses paralleled known distributions of
excitatory and inhibitory synapses, suggesting neuronal underpinnings.
Additionally, the RBC speed response consistently returned to baseline more
promptly than RBC content after the stimulus across cortical layers, supporting a
"flow-volume mismatch" of hemodynamic origin.
PMID- 25111473
TI - Multi-label segmentation of white matter structures: application to neonatal
brains.
AB - Accurate and consistent segmentation of brain white matter bundles at neonatal
stage plays an important role in understanding brain development and detecting
white matter abnormalities for the prediction of psychiatric disorders. Due to
the complexity of white matter anatomy and the spatial resolution of diffusion
weighted MR imaging, multiple fiber bundles can pass through one voxel. The goal
of this study is to assign one or multiple anatomical labels of white matter
bundles to each voxel to reflect complex white matter anatomy of the neonatal
brain. For this, we develop a supervised multi-label k-nearest neighbor (ML-kNN)
classification algorithm in Riemannian diffusion tensor spaces. Our ML-kNN
considers diffusion tensors lying on the Log-Euclidean Riemannian manifold of
symmetric positive definite (SPD) matrices and their corresponding vector space
as feature space. The ML-kNN utilizes the maximum a posteriori (MAP) principle to
make the prediction of white matter labels by reasoning with the labeling
information derived from the neighbors without assuming any probabilistic
distribution of the features. We show that our approach automatically learns the
number of white matter bundles at a location and provides anatomical annotation
of the neonatal white matter. In addition, our approach also provides the binary
mask for individual white matter bundles to facilitate tract-based statistical
analysis in clinical studies. We apply this method to automatically segment 13
white matter bundles of the neonatal brain and examine the segmentation accuracy
against semi-manual labels derived from tractography.
PMID- 25111472
TI - Guiding functional connectivity estimation by structural connectivity in MEG: an
application to discrimination of conditions of mild cognitive impairment.
AB - Whole brain resting state connectivity is a promising biomarker that might help
to obtain an early diagnosis in many neurological diseases, such as dementia.
Inferring resting-state connectivity is often based on correlations, which are
sensitive to indirect connections, leading to an inaccurate representation of the
real backbone of the network. The precision matrix is a better representation for
whole brain connectivity, as it considers only direct connections. The network
structure can be estimated using the graphical lasso (GL), which achieves
sparsity through l1-regularization on the precision matrix. In this paper, we
propose a structural connectivity adaptive version of the GL, where weaker
anatomical connections are represented as stronger penalties on the corresponding
functional connections. We applied beamformer source reconstruction to the
resting state MEG recordings of 81 subjects, where 29 were healthy controls, 22
were single-domain amnestic Mild Cognitive Impaired (MCI), and 30 were multiple
domain amnestic MCI. An atlas-based anatomical parcellation of 66 regions was
obtained for each subject, and time series were assigned to each of the regions.
The fiber densities between the regions, obtained with deterministic tractography
from diffusion-weighted MRI, were used to define the anatomical connectivity.
Precision matrices were obtained with the region specific time series in five
different frequency bands. We compared our method with the traditional GL and a
functional adaptive version of the GL, in terms of log-likelihood and
classification accuracies between the three groups. We conclude that introducing
an anatomical prior improves the expressivity of the model and, in most cases,
leads to a better classification between groups.
PMID- 25111475
TI - The NOACs (novel oral anticoagulants) have landed!
PMID- 25111476
TI - Unravelling immune alterations in schizophrenia: can DNA methylation provide
clues?
PMID- 25111477
TI - Pathogenesis of CpG island methylator phenotype-positive colorectal cancers: role
of genetic alteration and colonic flora.
PMID- 25111474
TI - Threat-related learning relies on distinct dorsal prefrontal cortex network
connectivity.
AB - Conditioned changes in the emotional response to threat (e.g. aversive
unconditioned stimulus; UCS) are mediated in part by the prefrontal cortex (PFC).
Unpredictable threats elicit large emotional responses, while the response is
diminished when the threat is predictable. A better understanding of how PFC
connectivity to other brain regions varies with threat predictability would
provide important insights into the neural processes that mediate conditioned
diminution of the emotional response to threat. The present study examined brain
connectivity during predictable and unpredictable threat exposure using a fear
conditioning paradigm (previously published in Wood et al., 2012) in which
unconditioned functional magnetic resonance imaging data were reanalyzed to
assess effective connectivity. Granger causality analysis was performed using the
time series data from 15 activated regions of interest after hemodynamic
deconvolution, to determine regional effective connectivity. In addition,
connectivity path weights were correlated with trait anxiety measures to assess
the relationship between negative affect and brain connectivity. Results indicate
the dorsomedial PFC (dmPFC) serves as a neural hub that influences activity in
other brain regions when threats are unpredictable. In contrast, the dorsolateral
PFC (dlPFC) serves as a neural hub that influences the activity of other brain
regions when threats are predictable. These findings are consistent with the view
that the dmPFC coordinates brain activity to take action, perhaps in a reactive
manner, when an unpredicted threat is encountered, while the dlPFC coordinates
brain regions to take action, in what may be a more proactive manner, to respond
to predictable threats. Further, dlPFC connectivity to other brain regions (e.g.
ventromedial PFC, amygdala, and insula) varied with negative affect (i.e. trait
anxiety) when the UCS was predictable, suggesting that stronger connectivity may
be required for emotion regulation in individuals with higher levels of negative
affect.
PMID- 25111478
TI - Epigenetic traits of testicular cancer: from primordial germ cells to germ cell
tumors.
PMID- 25111480
TI - Remodeling and spacing factor 1 (RSF1): a rising star in DNA repair.
PMID- 25111481
TI - Specific inhibition of DNMT1/CFP1 reduces cancer phenotypes and enhances
chemotherapy effectiveness.
AB - AIM: DNA methylation is a fundamental biologic process of genomes and is a
candidate for pharmacological manipulation that might have important therapeutic
advantages. Thus, DNA methyltransferases (DNMTs) appear to be ideal targets for
drug intervention. MATERIALS & METHODS: To develop a new generation of DNMT
inhibitor, we analyzed the ability of peptides to selectively inhibit certain
DNMT1-incuding complexes. RESULTS: Our study demonstrates that the disruption of
DNMT1/CFP1-including complexes increases the efficiency of chemotherapeutic
treatment on established tumors in mice. CONCLUSION: Our data opens a promising
and innovative alternative to the development of DNMT inhibitors.
PMID- 25111482
TI - The KDM5 family of histone demethylases as targets in oncology drug discovery.
AB - There is growing evidence for a causal role of the KDM5 family of histone
demethylases in human cancer. In particular, KDM5A (JARID1A/RBP2) and KDM5B
(JARID1B/PLU1) contribute to cancer cell proliferation, reduce the expression of
tumor suppressor genes, promote the development of drug tolerance and maintain
tumor-initiating cells. KDM5 enzymes remove tri- and di-methylations of lysine 4
of histone H3 - modifications that occur at the start site of transcription in
actively transcribed genes. However, the importance of the histone demethylase
activity of KDM5 proteins for cancer cells has not been resolved so far. The
currently available approaches suppress or remove the targeted proteins and
thereby affect their putative functions as structural components and recruitment
factors for other chromatin-associated proteins. Therefore, the development of
specific enzymatic inhibitors for KDM5 will promote our understanding of the
biological role of their catalytic activity and yield potential novel anticancer
therapeutics.
PMID- 25111483
TI - Epigenetic modifications as novel therapeutic targets for Huntington's disease.
AB - Huntington's disease is a late-onset, autosomal dominant neurodegenerative
disorder characterized by motor, cognitive and psychiatric symptomatology. The
earliest stage of Huntington's disease is marked by alterations in gene
expression, which partially results from dysregulated epigenetic modifications.
In past decades, altered epigenetic markers including histone modifications
(acetylation, methylation, ubiquitylation and phosphorylation) and DNA
modifications (cytosine methylation and hydroxymethylation) have been reported as
important epigenetic features in patients and multiple animal models of
Huntington's disease. Drugs aimed to correct some of those alterations have shown
promise in treating Huntington's disease. This article discusses the field of
epigenetics for potential Huntington's disease interventions and presents the
most recent findings in this area.
PMID- 25111484
TI - Using epigenomic studies in monozygotic twins to improve our understanding of
cancer.
AB - Cancer is a set of diseases that exhibit not only genetic mutations but also a
profoundly distorted epigenetic landscape. Over the last two decades, great
advances have been made in identifying these alterations and their importance in
the initiation and progression of cancer. Epigenetic changes can be seen from the
very early stages in tumorigenesis and dysregulation of the epigenome has an
increasingly acknowledged pathogenic role. Epigenomic twin studies have great
potential to contribute to our understanding of complex diseases, such as cancer.
This is because the use of monozygotic twins discordant for cancer enables
epigenetic variation analysis without the confounding influence of the
constitutive genetic background, age or cohort effects. It therefore allows the
identification of susceptibility loci that may be sensitive to modification by
the environment. These studies into cancer etiology will potentially lead to
robust epigenetic markers for the detection and risk assessment of cancer.
PMID- 25111485
TI - DNA methylation markers for early detection of women's cancer: promise and
challenges.
AB - Breast, ovarian and endometrial cancers cause significant morbidity and
mortality. Despite the presence of existing screening, diagnostic and treatment
modalities, they continue to pose considerable unsolved challenges. Overdiagnosis
is a growing problem in breast cancer screening and neither screening nor early
diagnosis of ovarian or endometrial cancer is currently possible. Moreover,
treatment of the diversity of these cancers presenting in the clinic is not
sufficiently personalized at present. Recent technological advances, including
reduced representation bisulfite sequencing, methylation arrays, digital PCR,
next-generation sequencing and advanced statistical data analysis, enable the
analysis of methylation patterns in cell-free tumor DNA in serum/plasma. Ongoing
work is bringing these methods together for the analysis of samples from large
clinical trials, which have been collected well in advance of cancer diagnosis.
These efforts pave the way for the development of a noninvasive method that would
enable us to overcome existing challenges to personalized medicine.
PMID- 25111487
TI - EZH2 as a potential target in cancer therapy.
AB - Over the last several years, dysregulation of epigenetic mechanisms including DNA
and histone methylation has been recognized as a hallmark of cancer. Alterations
of epigenetic regulators themselves, including the histone lysine
methyltransferase EZH2, have been reported in numerous cancer types. With the
discovery of small molecule inhibitors of EZH2, we can now begin to evaluate EZH2
as a therapeutic target in cancer. This article will provide an overview of the
dysregulation of EZH2 in cancer, possible mechanisms for inhibition of EZH2
activity, and the preclinical activity of currently available EZH2 inhibitors.
PMID- 25111488
TI - Active DNA demethylation of the vertebrate genomes by DNA methyltransferases:
deaminase, dehydroxymethylase or demethylase?
AB - Vertebrate DNA methyltransferases (DNMTs) have been thought to primarily function
to covalently add a methyl group to the 5-position of cytosine. However, recent
discovery of the DNA demethylation and dehydroxymethylation activities of DNMTs
in vitro suggest new routes to complete the dynamic cycle of DNA methylation
demethylation of the vertebrate genomes. The in vitro reaction conditions suggest
that vertebrate DNMTs can switch from DNA methylases to DNA dehydroxymethylases
under oxidative stress and to DNA demethylases in the presence of calcium ion
under nonreducing conditions. These environmental parameters provide clues
regarding the choices in vivo of DNMT activities utilized in different
physiological systems. In particular, the nature of these parameters suggest that
the DNA demethylation and dehydroxymethylation activities of the vertebrate DNMTs
play essential roles in multiple biological processes including early embryo
development, regulation of neuronal plasticity, tumorigenesis and hormone
regulated transcription.
PMID- 25111486
TI - Functions of SAGA in development and disease.
AB - Precise regulation of gene expression programs during embryo development requires
cooperation between transcriptional factors and histone-modifying enzymes, such
as the Gcn5 histone acetyltransferase. Gcn5 functions within a multi-subunit
complex, called SAGA, that is recruited to specific genes through interactions
with sequence-specific DNA-binding proteins to aid in gene activation. Although
the transcriptional programs regulated by SAGA in embryos are not well defined,
deletion of either Gcn5 or USP22, the catalytic subunit of a deubiquitinase
module in SAGA, leads to early embryonic lethality. Here, we review the known
functions of Gcn5, USP22 and associated proteins during development and discuss
how these functions might be related to human disease states, including cancer
and neurodegenerative diseases.
PMID- 25111490
TI - Thermal conductivity of graphene laminate.
AB - We have investigated thermal conductivity of graphene laminate films deposited on
polyethylene terephthalate substrates. Two types of graphene laminate were
studied, as deposited and compressed, in order to determine the physical
parameters affecting the heat conduction the most. The measurements were
performed using the optothermal Raman technique and a set of suspended samples
with the graphene laminate thickness from 9 to 44 MUm. The thermal conductivity
of graphene laminate was found to be in the range from 40 to 90 W/mK at room
temperature. It was found unexpectedly that the average size and the alignment of
graphene flakes are more important parameters defining the heat conduction than
the mass density of the graphene laminate. The thermal conductivity scales up
linearly with the average graphene flake size in both uncompressed and compressed
laminates. The compressed laminates have higher thermal conductivity for the same
average flake size owing to better flake alignment. Coating plastic materials
with thin graphene laminate films that have up to 600* higher thermal
conductivity than plastics may have important practical implications.
PMID- 25111489
TI - Multicellular architecture of malignant breast epithelia influences mechanics.
AB - Cell-matrix and cell-cell mechanosensing are important in many cellular
processes, particularly for epithelial cells. A crucial question, which remains
unexplored, is how the mechanical microenvironment is altered as a result of
changes to multicellular tissue structure during cancer progression. In this
study, we investigated the influence of the multicellular tissue architecture on
mechanical properties of the epithelial component of the mammary acinus. Using
creep compression tests on multicellular breast epithelial structures, we found
that pre-malignant acini with no lumen (MCF10AT) were significantly stiffer than
normal hollow acini (MCF10A) by 60%. This difference depended on structural
changes in the pre-malignant acini, as neither single cells nor normal
multicellular acini tested before lumen formation exhibited these differences. To
understand these differences, we simulated the deformation of the acini with
different multicellular architectures and calculated their mechanical properties;
our results suggest that lumen filling alone can explain the experimentally
observed stiffness increase. We also simulated a single contracting cell in
different multicellular architectures and found that lumen filling led to a 20%
increase in the "perceived stiffness" of a single contracting cell independent of
any changes to matrix mechanics. Our results suggest that lumen filling in
carcinogenesis alters the mechanical microenvironment in multicellular epithelial
structures, a phenotype that may cause downstream disruptions to mechanosensing.
PMID- 25111491
TI - Editorial: European Symposium on BioPolymers.
PMID- 25111492
TI - Minocycline encapsulated chitosan nanoparticles for central antinociceptive
activity.
AB - The purpose of the study is to explore the central anti-nociceptive activity of
brain targeted nanoparticles (NP) of minocycline hydrochloride (MH). The NP were
formulated using the modified ionotropic gelation method (MHNP) and were coated
with Tween 80 (T80) to target them to brain (cMHNP). The formulated nanoparticles
have already been characterized for particle size, zeta potential, drug
entrapment efficiency and in vitro drug release. The nanoparticles were then
evaluated for pharmacodynamic activity using thermal methods. The pure drug and
the formulation, MHNP were not able to show a statistically significant central
analgesic activity. cMHNP on the other hand evidenced a significant central
analgesic activity. Animal models evidenced that brain targeted nanoparticles may
be utilized for effective delivery of central anti-nociceptive effect of MH.
Further clinical studies are required to explore the activity for mankind.
PMID- 25111493
TI - Extraction optimization of polysaccharide from Zanthoxylum bungeanum using RSM
and its antioxidant activity.
AB - Polysaccharide prepared from pericarp of Zanthoxylum bungeanum was proved to
possess excellent antioxidant activities in vitro by using reducing ferric iron
power, DPPH radical scavenging activity, chelating ferrous iron capacity, and
hydroxyl radical scavenging activity assays in the present study. In those four
antioxidant assay models, Z. bungeanum polysaccharide (ZBP) displayed prominent
antioxidant activities with low EC50 values of 0.011, 0.021, 0.056 and 0.008
mg/mL, respectively. Moreover, the extraction process of ZBP was further
optimized by response surface methodology combined with Box-Behnken design. The
highest polysaccharide yield 13.96%, which agreed closely with the predicted
yield 13.20%, was obtained under the optimal extraction conditions as follows:
extraction temperature 89 degrees C, extraction time 3h, ratio of water volume
(mL) to raw material weight (g) 29 (v/w), and extraction number two times. The
present research not only provide theoretical basis for exploitation of natural
polysaccharide antioxidants, but also establish the foundation of large-scale
production and further system utilization of ZBP.
PMID- 25111494
TI - Preparation of amidated derivatives of carboxymethylcellulose.
AB - Carboxymethylcellulose (CMC) was selected as substrate for amidation based on
previous results described for monocarboxy cellulose (MCC) with the aim to
prepare highly substituted products. In comparison with MCC containing uronic
carboxyl groups at C-6 position, O-carboxymethyl groups in CMC should be more
accessible for reagents because they are more distant from the polysaccharide
chain. Two-step way of amidation was based on the esterification of CMC carboxyls
by reaction with methanol and further amino-de-alkoxylation (aminolysis) of the
obtained methyl ester with amidation reagents (n-alkylamines, hydrazine and
hydroxylamine). Purity and substitution degree of the products were monitored by
the vibration spectroscopic methods (FTIR and Raman) and organic elemental
analysis. Analytical methods confirmed the preparation of highly or moderately
substituted N-alkylamides, hydrazide and hydroxamic acid of CMC.
PMID- 25111495
TI - Metal ion-induced alginate-locust bean gum IPN microspheres for sustained oral
delivery of aceclofenac.
AB - The alginate microspheres represent a useful tool for sustained oral delivery of
drugs but exhibit several problems associated with the stability and rapid
release of drugs at higher pH values. To overcome these drawbacks, alginate
locust bean gum (LBG) interpenetrating microspheres were prepared by calcium ion
(Ca(+2)) induced ionotropic gelation technique for prolonged release of
aceclofenac. The drug entrapment efficiency of these microspheres was found to be
59-93%. The microspheres lied in the size range of 406-684MUm. Scanning electron
microscopy revealed spherical shape of the microspheres. No drug-polymer
interaction was evident after infrared spectroscopy analysis. The microspheres
provided sustained release of aceclofenac in phosphate buffer solution (pH 6.8)
over a period of 8h. The drug release data were fitted into the Korsmeyer-Peppas
model and the drug release was found to follow anomalous (non-Fickian) diffusion
mechanism. Pharmacodynamic study of the microspheres showed a prolonged anti
inflammatory activity in carrageenan-induced rat paw model following oral
administration.
PMID- 25111497
TI - A contact-imaging based microfluidic cytometer with machine-learning for single
frame super-resolution processing.
AB - Lensless microfluidic imaging with super-resolution processing has become a
promising solution to miniaturize the conventional flow cytometer for point-of
care applications. The previous multi-frame super-resolution processing system
can improve resolution but has limited cell flow rate and hence low throughput
when capturing multiple subpixel-shifted cell images. This paper introduces a
single-frame super-resolution processing with on-line machine-learning for
contact images of cells. A corresponding contact-imaging based microfluidic
cytometer prototype is demonstrated for cell recognition and counting. Compared
with commercial flow cytometer, less than 8% error is observed for absolute
number of microbeads; and 0.10 coefficient of variation is observed for cell
ratio of mixed RBC and HepG2 cells in solution.
PMID- 25111496
TI - Role for heat shock protein 90alpha in the proliferation and migration of HaCaT
cells and in the deep second-degree burn wound healing in mice.
AB - Inflammation, proliferation, and tissue remodeling are essential steps for wound
healing. The hypoxic wound microenvironment promotes cell migration through a
hypoxia--heat shock protein 90 alpha (Hsp90alpha)--low density lipoprotein
receptor-related protein-1 (LRP-1) autocrine loop. To elucidate the role of this
autocrine loop on burn wound healing, we investigated the expression profile of
Hsp90alpha at the edge of burn wounds and found a transient increase in both mRNA
and protein levels. Experiments performed with a human keratinocyte cell line-
HaCaT also confirmed above results. 17-dimethylaminoethylamino
17demethoxygeldanamycin hydrochloride (17-DMAG), an Hsp90alpha inhibitor, was
used to further evaluate the function of Hsp90alpha in wound healing.
Consistently, topical application of Hsp90alpha in the early stage of deep second
degree burn wounds led to reduced inflammation and increased tissue granulation,
with a concomitant reduction in the size of the wound at each time point tested
(p<0.05). Consequently, epidermal cells at the wound margin progressed more
rapidly causing an expedited healing process. In conclusion, these results
provided a rationale for the therapeutic effect of Hsp90alpha on the burn wound
management.
PMID- 25111498
TI - Enhanced fluorescence of gold nanoclusters composed of HAuCl4 and histidine by
glutathione: glutathione detection and selective cancer cell imaging.
AB - Glutathione (GSH) can significantly and selectively enhance the fluorescence
intensity of Au nanoclusters (NCs) prepared by blending HAuCl4 and histidine in
solution. The quantum yield of the Au NCs after adding GSH can reach above 10%.
Besides, GSH capping shifts the excitation peak of Au NCs from ultraviolet (386
nm) to visible light (414 nm) and improves the stability of the Au NCs. The
cytotoxicities of the Au NCs with and without GSH for normal lung cells (ATII)
and cancerous lung cells (A549) are evaluated. The GSH-capped Au NCs have much
less cytotoxicity to both normal and cancer cells, as compared to those without
GSH. For Au NCs without GSH, less cytotoxicity is observed in cancer cells than
in normal cells. In addtion, the Au NCs can selectively detect GSH over cysteine
and homocysteine, the two biothiols which commonly exist in cells that can
seriously affect GSH detection. Most importantly, Au NCs without GSH can
selectively image the cancer cells, especially for the liver cancer cells whose
GSH content is much higher than other cell types. This property makes the Au NCs
a powerful probe to distinguish cancer cells from normal cells.
PMID- 25111499
TI - Prognostic value of cardiac troponin in patients with chronic kidney disease
without suspected acute coronary syndrome: a systematic review and meta-analysis.
AB - BACKGROUND: Clinicians face uncertainty about the prognostic value of troponin
testing in patients with chronic kidney disease (CKD) without suspected acute
coronary syndrome (ACS). PURPOSE: To systematically review the literature on
troponin testing in patients with CKD without ACS. DATA SOURCES: MEDLINE, EMBASE,
and the Cochrane Central Register of Controlled Trials through May 2014. STUDY
SELECTION: Studies examining elevated versus normal troponin levels in patients
with CKD without ACS. DATA EXTRACTION: Paired reviewers selected articles for
inclusion, extracted data, and graded strength of evidence (SOE). Meta-analyses
were conducted when studies had sufficient homogeneity of key variables. DATA
SYNTHESIS: Ninety-eight studies met inclusion criteria. Elevated troponin levels
were associated with all-cause and cardiovascular mortality among patients
receiving dialysis (moderate SOE). Pooled hazard ratios (HRs) for all-cause
mortality from studies that adjusted for age and coronary artery disease or a
risk equivalent were 3.0 (95% CI, 2.4 to 4.3) for troponin T and 2.7 (CI, 1.9 to
4.6) for troponin I. The pooled adjusted HRs for cardiovascular mortality were
3.3 (CI, 1.8 to 5.4) for troponin T and 4.2 (CI, 2.0 to 9.2) for troponin I.
Findings were similar for patients with CKD who were not receiving dialysis, but
there were fewer studies. No study tested treatment strategies by troponin cut
points. LIMITATION: Studies were heterogeneous regarding assays, troponin cut
points, covariate adjustment, and follow-up. CONCLUSION: In patients with CKD
without suspected ACS, elevated troponin levels were associated with worse
prognosis. Future studies should focus on whether this biomarker is more
appropriate than clinical models for reclassifying risk of patients with CKD and
whether such classification can help guide treatment in those at highest risk for
death. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.
PMID- 25111501
TI - Cryptosporidium species in humans and animals: current understanding and research
needs.
AB - Cryptosporidium is increasingly recognized as one of the major causes of moderate
to severe diarrhoea in developing countries. With treatment options limited,
control relies on knowledge of the biology and transmission of the members of the
genus responsible for disease. Currently, 26 species are recognized as valid on
the basis of morphological, biological and molecular data. Of the nearly 20
Cryptosporidium species and genotypes that have been reported in humans,
Cryptosporidium hominis and Cryptosporidium parvum are responsible for the
majority of infections. Livestock, particularly cattle, are one of the most
important reservoirs of zoonotic infections. Domesticated and wild animals can
each be infected with several Cryptosporidium species or genotypes that have only
a narrow host range and therefore have no major public health significance.
Recent advances in next-generation sequencing techniques will significantly
improve our understanding of the taxonomy and transmission of Cryptosporidium
species, and the investigation of outbreaks and monitoring of emerging and
virulent subtypes. Important research gaps remain including a lack of subtyping
tools for many Cryptosporidium species of public and veterinary health
importance, and poor understanding of the genetic determinants of host
specificity of Cryptosporidium species and impact of climate change on the
transmission of Cryptosporidium.
PMID- 25111500
TI - Neuromelanin magnetic resonance imaging reveals increased dopaminergic neuron
activity in the substantia nigra of patients with schizophrenia.
AB - PURPOSE: The dopamine hypothesis suggests that excessive dopamine release results
in the symptoms of schizophrenia. The purpose of this study was to elucidate the
dopaminergic and noradrenergic neurons using 3-T neuromelanin magnetic resonance
imaging (MRI) in patients with schizophrenia and healthy control subjects.
METHODS: We prospectively examined 52 patients with schizophrenia (M: F = 27?25,
mean age, 35 years) and age- and sex-matched healthy controls. Using a 3T MRI
unit, we obtained oblique T1-weighted axial images perpendicular to the
brainstem. We measured the signal intensity and area for the substantia nigra
(SNc), midbrain tegmentum, locus ceruleus (LC), and pons. We then calculated the
contrast ratios (CR) for the SNc (CRSN) and LC (CRLC), which were compared
between patients and healthy controls using unpaired t-tests. RESULTS: The SNc
and LC were readily identified in both patients and healthy controls as areas
with high signal intensities in the posterior part of the cerebral peduncle and
in the upper pontine tegmentum. The CRSN values in patients were significantly
higher than those in healthy controls (10.89+/-2.37 vs. 9.6+/-2.36, p<0.01). We
observed no difference in the CRLC values between the patients and healthy
controls (14.21+/-3.5 vs. 13.44+/-3.37, p = 0.25). Furthermore, there was no
difference in area of the SNc and LC between schizophrenia patients and controls.
CONCLUSIONS: Neuromelanin MRI might reveal increased signal intensity in the SNc
of patients with schizophrenia. Our results indicate the presence of excessive
dopamine products in the SNc of these patients.
PMID- 25111502
TI - Oxygen-driven competition between low-dimensional structures of Sr3CoMO6 and
Sr3CoMO7-delta with M = Ru, Ir.
AB - We have realized a reversible structure transformation of one-dimensional 1D
K4CdCl6-type Sr3CoMO6 with the Co(2+)/M(4+) cation ordering into the two
dimensional 2D double layered Ruddlesden-Popper structure Sr3CoMO7-delta with a
random distribution of Co and M (with M = Ru, Ir) upon increasing the partial
oxygen pressure. The combined soft and hard X-ray absorption spectroscopy studies
show that under transformation, Co and M cations were oxidized to Co(3+) and
M(5+). During oxidation, high-spin Co(2+) in Sr3CoMO6 first transforms into high
spin Co(3+) in oxygen-deficient Sr3CoMO7-delta, and then further transforms into
low-spin Co(3+) in fully oxidized Sr3CoMO7 upon further increasing the partial
pressure of oxygen. The 1D Sr3CoMO6 compound is magnetically ordered at low
temperatures with the magnetic moments lying along the c-axis. Their alignment is
parallel for Sr3CoRuO6 and antiparallel for Sr3CoIrO6. The 2D compounds reveal a
spin-glass-like behavior related to the random distribution of magnetic cations
in the structure.
PMID- 25111503
TI - Cutaneous sensory function is not related to depression and anxiety in patients
with chronic pruritus with dysesthetic subqualities.
AB - The objective of this study was to examine the subgroup of patients with chronic
pruritus with dysesthetic subqualities for the presence of psychiatric
comorbidities and to evaluate whether anxiety and depression make a difference in
perception of somatosensory stimuli in quantitative sensory testing (QST). Forty
nine patients underwent routine diagnostics, a standardised QST testing battery,
a psychosomatic evaluation for psychic comorbidities and filled out 2
questionnaires: the Patient Health Questionnaire for the assessment of depressive
mood and the State Trait Anxiety Inventory. Twenty-seven (55.1%) of the sample
had at least one psychiatric comorbid diagnosis. QST parameters were not
correlated to anxiety and depression levels. We conclude that psychosomatic
evaluation should become part of routine diagnostics of these patients in order
to detect and treat psychiatric comorbidity. However, research on somatosensory
aspects in these patients seems not to be affected by the levels of anxiety and
depression.
PMID- 25111505
TI - Synthesis and cytotoxic activity of 1-{3-[1-(5-organylsilylfuran-2-yl)silinan-1
yl]propyl}amines and some trimethylgermyl analogues.
AB - New highly cytotoxic 1-{3-[1-(5-organylsilyl-furan-2-yl)silinan-1
yl]propyl}amines and some trimethylgermyl analogues (IC50 1-7 MUg mL(-1)) have
been synthesized by a hydrosilylation reaction of aliphatic and heterocyclic N
allylamines in the presence of Speier's catalyst. The effects of the silacycle,
the element-organic substituent in position 5 of the furan ring, and the
structure of the amine on the cytotoxicity of the new compounds have been
studied.
PMID- 25111504
TI - Inhibition of breast cancer resistance protein (ABCG2) in human myeloid dendritic
cells induces potent tolerogenic functions during LPS stimulation.
AB - Breast cancer resistance protein (ABCG2), a member of the ATP-binding cassette
transporters has been identified as a major determinant of multidrug resistance
(MDR) in cancer cells, but ABC transporter inhibition has limited therapeutic
value in vivo. In this research, we demonstrated that inhibition of efflux
transporters ABCG2 induced the generation of tolerogenic DCs from human
peripheral blood myeloid DCs (mDCs). ABCG2 expression was present in mDCs and was
further increased by LPS stimulation. Treatment of CD1c+ mDCs with an ABCG2
inhibitor, Ko143, during LPS stimulation caused increased production of IL-10 and
decreased production of pro-inflammatory cytokines and decreased expression of
CD83 and CD86. Moreover, inhibition of ABCG2 in monocyte-derived DCs (MDDCs)
abrogated the up-regulation of co-stimulatory molecules and production of pro
inflammatory cytokines in these cells in response to LPS. Furthermore, CD1c+ mDCs
stimulated with LPS plus Ko143 inhibited the proliferation of allogeneic and
superantigen-specific syngenic CD4+ T cells and promoted expansion of CD25+FOXP3+
regulatory T (Treg) cells in an IL-10-dependent fashion. These tolerogenic
effects of ABCG2 inhibition could be abolished by ERK inhibition. Thus, we
demonstrated that inhibition of ABCG2 in LPS-stimulated mDCs can potently induce
tolerogenic potentials in these cells, providing crucial new information that
could lead to development of better strategies to combat MDR cancer.
PMID- 25111506
TI - Mitigating phototoxicity during multiphoton microscopy of live Drosophila embryos
in the 1.0-1.2 um wavelength range.
AB - Light-induced toxicity is a fundamental bottleneck in microscopic imaging of live
embryos. In this article, after a review of photodamage mechanisms in cells and
tissues, we assess photo-perturbation under illumination conditions relevant for
point-scanning multiphoton imaging of live Drosophila embryos. We use third
harmonic generation (THG) imaging of developmental processes in embryos excited
by pulsed near-infrared light in the 1.0-1.2 um range. We study the influence of
imaging rate, wavelength, and pulse duration on the short-term and long-term
perturbation of development and define criteria for safe imaging. We show that
under illumination conditions typical for multiphoton imaging, photodamage in
this system arises through 2- and/or 3-photon absorption processes and in a
cumulative manner. Based on this analysis, we derive general guidelines for
improving the signal-to-damage ratio in two-photon (2PEF/SHG) or THG imaging by
adjusting the pulse duration and/or the imaging rate. Finally, we report label
free time-lapse 3D THG imaging of gastrulating Drosophila embryos with sampling
appropriate for the visualisation of morphogenetic movements in wild-type and
mutant embryos, and long-term multiharmonic (THG-SHG) imaging of development
until hatching.
PMID- 25111507
TI - Ethnicity is an independent determinant of age-specific PSA level: findings from
a multiethnic Asian setting.
AB - OBJECTIVES: To study the baseline PSA profile and determine the factors
influencing the PSA levels within a multiethnic Asian setting. MATERIALS AND
METHODS: We conducted a cross-sectional study of 1054 men with no clinical
evidence of prostate cancer, prostate surgery or 5alpha-reductase inhibitor
treatment of known prostate conditions. The serum PSA concentration of each
subject was assayed. Potential factors associated with PSA level including age,
ethnicity, height, weight, family history of prostate cancer, lower urinary tract
voiding symptoms (LUTS), prostate volume and digital rectal examination (DRE)
were evaluated using univariable and multivariable analysis. RESULTS: There were
38 men (3.6%) found to have a PSA level above 4 ng/ml and 1016 (96.4%) with a
healthy PSA (<=4 ng/ml). The median PSA level of Malay, Chinese and Indian men
was 1.00 ng/ml, 1.16 ng/ml and 0.83 ng/ml, respectively. Indians had a relatively
lower median PSA level and prostate volume than Malays and Chinese, who shared a
comparable median PSA value across all 10-years age groups. The PSA density was
fairly similar amongst all ethnicities. Further analysis showed that ethnicity,
weight and prostate volume were independent factors associated with age specific
PSA level in the multivariable analysis (p<0.05). CONCLUSION: These findings
support the concept that the baseline PSA level varies between different
ethnicities across all age groups. In addition to age and prostate volume,
ethnicity may also need to be taken into account when investigating serum PSA
concentrations in the multiethnic Asian population.
PMID- 25111508
TI - Phytochemical study of Caulerpa racemosa (Forsk.) J. Agarth, an invading alga in
the habitat of La Maddalena Archipelago.
AB - Caulerpa racemosa is a marine Chlorophyta widely distributed in tropical areas,
introduced into the Mediterranean Sea since 1990. It has been invading the
Mediterranean Sea causing ecological problems. This invasive event can be
considered as one of the most serious in the history of species introduced into
the Mediterranean Sea, even if C. racemosa has not triggered as much attention as
the famous 'killer alga' Caulerpa taxifolia. The aim of this work is to analyse
phytochemically C. racemosa in the northern Sardinia area for secondary
metabolites. Marine algae shows the molecular pattern of bis-indole alkaloids,
sesquiterpenes, diterpenes and sterols. The intention is to expand phytochemical
analysis in order to understand just how significant the anti-tumour, anti
inflammatory and antinociceptive actions can be.
PMID- 25111510
TI - Analysis of post-transplant chimerism by using a single amplification reaction of
38 Indel polymorphic loci.
AB - In order to detect chimerism after allogeneic hematopoietic SCT (HSCT), several
methods have been developed. In this study we describe the use of a set of
insertion/deletion (Indel) polymorphic loci to determine the level of donor cell
engraftment. We analyzed 50 DNA samples from patients who had undergone HSCT, and
also several artificial chimeric samples created by mixing different DNA
specimens from non-transplanted donors in various proportions. A specific set of
38 autosomic Indel polymorphisms were analyzed. For comparison purposes, a set of
15 short tandem repeats (STRs) were analyzed using the Identifiler Plus
Amplification Kit. Our results suggest that Indel-based and STR-based procedures
behave similarly in most cases. However, Indel analysis may provide additional
information in some cases with a small minor chimeric component or when the
presence of stutter bands complicates chimerism estimation.
PMID- 25111509
TI - T helper subsets in allergic eye disease.
AB - PURPOSE OF REVIEW: Ocular allergy is an IgE-mediated disease that results in
inflammation of the conjunctiva and, in more severe cases, the cornea. This is
driven by an immediate hypersensitivity response via mast cells, followed by a
late phase response mediated by eosinophils both of which are indeed dependent on
T helper (Th) lymphocyte activity. Here, we provide an update on Th subsets [Th1,
Th2, Th17, and T regulatory (Treg)] and their relevance in ocular allergy. RECENT
FINDINGS: Recent evidence in ocular allergy points to an involvement of other Th
subsets, in addition to Th2. However, how these subsets are activated and their
role in mediating the different clinical forms is poorly understood. Novel mouse
models may facilitate addressing such unknowns, and future challenges will
involve how to translate such findings into more effective and 'patho-specific'
treatments. SUMMARY: Ocular allergy, especially in severe forms, involves subsets
other than Th2. Th1 cells have been detected in mild and severe forms, and recent
evidence points to a possible role for IL-17 in severe disease. Tregs, on the
other hand, dampen pathogenic Th cell function and allergy immunotherapy is
associated with Treg augmentation in disease management. Further understanding of
Th biology is warranted and may lead to better therapies.
PMID- 25111511
TI - Impact of pretransplant body mass index on the clinical outcome after allogeneic
hematopoietic SCT.
AB - To elucidate the impact of pretransplant body mass index (BMI) on the clinical
outcome, we performed a retrospective study with registry data including a total
of 12 050 patients (age ?18 years) who received allogeneic hematopoietic SCT
(HSCT) between 2000 and 2010. Patients were stratified as follows: BMI<18.5
kg/m(2), Underweight, n=1791; 18.5?BMI<25, Normal, n=8444; 25?BMI<30, Overweight,
n=1591; BMI?30, Obese, n=224. The median age was 45 years (range, 18-77). A
multivariate analysis showed that the risk of relapse was significantly higher in
the underweight group and lower in the overweight and obese groups compared with
the normal group (hazard ratio (HR), 1.16, 0.86, and 0.74, respectively). The
risk of GVHD was significantly higher in the overweight group compared with the
normal group. The risk of non-relapse mortality (NRM) was significantly higher in
the overweight and obese group compared with the normal group (HR 1.19 and HR
1.43, respectively). The probability of OS was lower in the underweight group
compared with the normal group (HR 1.10, P=0.018). In conclusion, pretransplant
BMI affected the risk of relapse and NRM after allogeneic HSCT. Underweight was a
risk factor for poor OS because of an increased risk of relapse. Obesity was a
risk factor for NRM.
PMID- 25111512
TI - Identification of molecular and cytogenetic risk factors for unfavorable core
binding factor-positive adult AML with post-remission treatment outcome analysis
including transplantation.
AB - Emerging molecular studies have identified a subgroup of patients with
unfavorable core-binding factor-positive (CBF)-AML who should be treated by
intensified post-remission treatments. We analyzed 264 adults with CBF-AML from
2002 to 2011, and focused on 206 patients who achieved CR after standard '3+7'
induction chemotherapy. Patients who achieved CR with an available donor were
treated with allogeneic hematopoietic SCT (allo-HSCT, n=115) and the rest were
treated with autologous (auto) HSCT (n=72) or chemotherapy alone (n=19). OS was
not significantly different between CBFbeta/MYH11 (n=62) and RUNX1/RUNX1T1
(n=144), and auto-HSCT showed favorable OS compared with allo-HSCT or
chemotherapy alone. Cytogenetic analysis identified that inv(16) without trisomy
had a favorable OS and t(8;21) with additional chromosomes had an unfavorable OS,
but multivariate analysis revealed those were NS. Patients with c-kit mutation
showed inferior OS. For transplanted patients, residual post-transplant CBF
minimal residual disease quantitative PCR with higher WT1 expression at D+60
showed the worst OS with a higher incidence of relapse. Conclusively, we found
that unfavorable CBF-AML can be defined with risk stratification using
cytogenetic and molecular studies, and a careful risk-adapted treatment approach
using frontline transplantation with novel therapies should be evaluated for this
particular risk subgroup.
PMID- 25111513
TI - BAT2 and BAT3 polymorphisms as novel genetic risk factors for rejection after HLA
related SCT.
AB - The genetic background of donor and recipient is an important factor determining
the outcome of allogeneic hematopoietic SCT (allo-HSCT). We applied whole-genome
analysis to investigate genetic variants-other than HLA class I and II-associated
with negative outcome after HLA-identical sibling allo-HSCT in a cohort of 110
beta-Thalassemic patients. We identified two single-nucleotide polymorphisms
(SNPs) in BAT2 (A/G) and BAT3 (T/C) genes, SNP rs11538264 and SNP rs10484558,
both located in the HLA class III region, in strong linkage disequilibrium
between each other (R(2)=0.92). When considered as single SNP, none of them
reached a significant association with graft rejection (nominal P<0.00001 for
BAT2 SNP rs11538264, and P<0.0001 for BAT3 SNP rs10484558), whereas the BAT2/BAT3
A/C haplotype was present at significantly higher frequency in patients who
rejected as compared to those with functional graft (30.0% vs 2.6%, nominal
P=1.15 * 10(-8); and adjusted P=0.0071). The BAT2/BAT3 polymorphisms and
specifically the A/C haplotype may represent a novel immunogenetic factor
associated with graft rejection in patients undergoing allo-HSCT.
PMID- 25111514
TI - Outcomes of stem cell transplant patients with acute respiratory failure
requiring mechanical ventilation in the United States.
AB - SCT indications and procedures are increasing worldwide. We sought to estimate
the prevalence of acute respiratory failure (ARF) of any cause in hospitalized
SCT patients, and assess the impact of invasive mechanical ventilation (IMV) on
outcomes. We hypothesize that duration of IMV in such patients is an independent
predictor of higher mortality. We performed a retrospective analysis of the
largest all-payer hospitalization data set in the United States, Nationwide In
patient Sample for years 2004-2010. Of the 101 462 SCT hospitalizations, 6074
(6%) developed ARF and were the final cohort. Type of SCT with ARF included
autologous 1987 (32.7%), allogeneic 3467 (57.1%) and cord blood 655 (10.8%).
Duration of IMV included <96 h (17.1%) and ?96 h (41.1%). Overall in-hospital
mortality (IHM) was 50.6% (3075). Predictors of IHM were IMV <96 h (odds
ratio=3.42 (2.44-4.79), P<0.0001) or IMV ?96 h (OR=4.61 (3.17-6.70), P<0.0001).
Type of SCT, comorbid burden, gender, hospital-teaching status/bed size or
insurance did not influence IHM. IMV ?96 h was associated with higher hospital
charges (mean $762 515, 95% estimate 0.3991 (0.3123-0.4859), increase of $304
474, P<0.0001) and higher length of stay (mean 61.5 days, 95% estimate 0.2198
(0.1531-0.2866), increase of 13 days, P<0.0001). In conclusion, ARF in
hospitalized SCT patients is not an uncommon occurrence and is associated with
50% mortality. Duration of IMV (?96 h) was an independent predictor of higher
mortality rates. Hospital resource utilization was significant.
PMID- 25111515
TI - Aerobic exercise capacity at long-term follow-up after paediatric allogeneic
haematopoietic SCT.
AB - Peak oxygen uptake (VO2peak), a measure of aerobic exercise capacity, predicts
mortality and morbidity in healthy and diseased individuals. Our aim was to
determine VO2peak years after paediatric allogeneic haematopoietic SCT (HSCT) and
to identify associations with baseline patient and donor characteristics,
transplantation factors, pulmonary function and self-reported sports activity. In
this cross-sectional, population-based study, we measured VO2peak, spirometry and
diffusion capacity of the lung (DLCO) 3-10 years post HSCT. Z-scores were
calculated by reference values from healthy subjects. Self-reported hours of
sports activity were obtained by interview. We included 63 patients (mean age
(range) 14.4 (7-24) years). HSCT patients exhibited lower mean VO2peak (-1.42 z
score, 95% confidential interval (-1.7; -1.1)) compared with healthy subjects
(P<0.001). Sixteen patients (25%) had VO2peak values <-1.96 z-score. Low VO2peak
was associated with reduced forced expiratory volume in 1 s (R(2)=0.11, P=0.009),
reduced DLCO/VA (R(2)=0.09, P=0.01) and low physical activity (mean VO2peak z
score inactive group: -2.1 vs most active group: -1.1, P=0.02). No associations
between VO2peak and diagnosis, donor type or GvHD were found. Although causes for
reduced VO2peak may be multiple, our findings stress the need to focus on
physical activity post HSCT to prevent lifestyle diseases and improve quality of
life.
PMID- 25111516
TI - Risk factors for vancomycin-resistant enterococcus bacteremia and its influence
on survival after allogeneic hematopoietic cell transplantation.
AB - Vancomycin-resistant enterococcus (VRE) is a well-known infectious complication
among immunocompromised patients. We performed a retrospective analysis to
identify risk factors for the development of VRE bacteremia (VRE-B) within 15
months after allogeneic hematopoietic cell transplantation (alloHCT) and to
determine its prognostic importance for other post-transplant outcomes. Eight
hundred consecutive adult patients who underwent alloHCT for hematologic diseases
from 1997 to 2011 were included. Seventy-six (10%) developed VRE-B at a median of
46 days post transplant. Year of transplant, higher HCT comorbidity score, a
diagnosis of ALL, unrelated donor and umbilical cord blood donor were all
significant risk factors on multivariable analysis for the development of VRE-B.
Sixty-seven (88%) died within a median of 1.1 months after VRE-B, but only four
(6%) of these deaths were attributable to VRE. VRE-B was significantly associated
with worse OS (hazard ratio 4.28, 95% confidence interval 3.23-5.66, P<0.001) in
multivariable analysis. We conclude that the incidence of VRE-B after alloHCT has
increased over time and is highly associated with mortality, although not usually
attributable to VRE infection. Rather than being the cause, this may be a marker
for a complicated post-transplant course. Strategies to further enhance immune
reconstitution post transplant and strict adherence to infection prevention
measures are warranted.
PMID- 25111518
TI - Caecal rupture associated with Ogilvie syndrome following caesarean hysterectomy
due to morbidly adherent placenta.
PMID- 25111519
TI - Hysteroscopic management of an oblique vaginal septum in a virgin girl with a
rare variant of Herlyn-Werner-Wunderlich syndrome.
AB - STUDY OBJECTIVE: To demonstrate a technique for hysteroscopic diagnosis and
management of a rare variant of Herlyn-Werner-Wunderlich syndrome (HWWS) in a
virgin girl. DESIGN: Presentation of a rare variant of HWWS and a step-by-step
description of the technique using videos, images, and title slides (educative
video) (Canadian Task Force classification III). SETTING: HWWS is a congenital
anomaly of the urogenital tract, typically characterized by uterus didelphys,
obstructed hemivagina, and ipsilateral renal agenesis. Of HWWS cases, 11.5% are a
rare variant of the syndrome, with a septate bicollis uterus and obstructed
hemivagina. HWWS is often diagnosed in adolescent girls and virgin patients.
Early diagnosis and treatment should be achieved using a convenient, minimally
invasive, and effective surgical approach to prevent complications.
INTERVENTIONS: A 14-year-old virgin girl had aggressive cyclic dysmenorrhea for 7
months. We made a diagnosis of the non-classic HWWS variant: septate uterus with
double cervix, obstructed right hemivagina with hematocolpos, and unilateral
renal agenesis. Diagnostic hysteroscopy indicated a flat hemivaginal septum, left
cervix, and uterine cavity, but no right cervix or other associated channel.
Hysteroscopic incision of the bulging oblique vaginal septum was performed
medially from the most prominent point of the septum up to the left cervix and
then down to the low edge of the oblique septum. An inflated Foley catheter was
placed in the right hemivagina for 2 days to prevent adhesion of the incised
septum. Surgery was successful, and the intact hymen was preserved. The patient
has been symptom-free for 4 months after surgery. CONCLUSION: Hysteroscopic
incision of the oblique vaginal septum is a convenient, minimally invasive, and
effective approach for treating HWWS in adolescents with cyclic dysmenorrhea and
hematocolpos.
PMID- 25111521
TI - The Medially Migrating Intracanalicular Vestibular Schwannoma.
PMID- 25111517
TI - The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic
hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and
severe acute GVHD.
AB - Hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic
SCT (allo-HSCT). Several risk factors have been suggested including BU-containing
myeloablative conditioning, unrelated donors and GVHD, but these have not been
consistently reported. We conducted a retrospective study including 339 allo-HSCT
recipients between 2009 and 2012. Of 339 patients, 79 (23.3%) developed HC with 2
year cumulative incidence of 24.0% (95% confidence interval, 19.4-28.9). The
median onset time was 45 days (range, 16-430) after allo-HSCT. Sixty-two patients
(84%) out of 74 evaluated for urine BK virus PCR testing showed a positive result
(mean 2.0 * 10(10) copies of DNA per mL). In univariate analysis, myeloablative
conditioning, HLA-mismatched donor, CMV viremia and acute GVHD (aGVHD) grade 3-4
were significantly associated with the risk of HC. Multivariate analysis
confirmed all associating factors identified in univariate analysis except for
HLA-mismatched donor: myeloablative conditioning (hazard ratio (HR) 2.63,
P=0.003), CMV viremia (HR 1.88, P=0.014) and aGVHD grade 3-4 (HR 1.71, P=0.029).
HC did not affect OS or non-relapse mortality. Symptomatic HC is a frequent
complication following allo-HSCT, with a 2-year cumulative incidence of 24.0%.
Three clinical factors associated with HC were identified including myeloablative
conditioning, CMV viremia and severe aGVHD.
PMID- 25111520
TI - Protein-engineered hydrogel encapsulation for 3-D culture of murine cochlea.
AB - HYPOTHESIS: Elastin-like protein (ELP) hydrogel helps maintain the three
dimensional (3-D) cochlear structure in culture. BACKGROUND: Whole-organ culture
of the cochlea is a useful model system facilitating manipulation and analysis of
live sensory cells and surrounding nonsensory cells. The precisely organized 3-D
cochlear structure demands a culture method that preserves this delicate
architecture; however, current methods have not been optimized to serve such a
purpose. METHODS: A protein-engineered ELP hydrogel was used to encapsulate organ
of Corti isolated from neonatal mice. Cultured cochleae were immunostained for
markers of hair cells and supporting cells. Organ of Corti hair cell and
supporting cell density and organ dimensions were compared between the ELP and
nonencapsulated systems. These culture systems were then compared with
noncultured cochlea. RESULTS: After 3 days in vitro, vital dye uptake and
immunostaining for sensory and nonsensory cells show that encapsulated cochlea
contain viable cells with an organized architecture. In comparison with
nonencapsulated cultured cochlea, ELP-encapsulated cochleae exhibit higher
densities of hair cells and supporting cells and taller and narrower organ of
Corti dimensions that more closely resemble those of noncultured cochleae.
However, we found compromised cell viability when the culture period extended
beyond 3 days. CONCLUSION: We conclude that the ELP hydrogel can help preserve
the 3-D architecture of neonatal cochlea in short-term culture, which may be
applicable to in vitro study of the physiology and pathophysiology of the inner
ear.
PMID- 25111522
TI - Round window stimulation for conductive and mixed hearing loss.
AB - OBJECTIVE: Assess surgical complications, postoperative residual hearing, and
speech perception outcomes of placement of a middle ear implant on the round
window in conductive and mixed hearing loss cases. STUDY DESIGN: Single-subject,
repeated-measures design where each subject served as his or her own control.
SETTING: Tertiary referral medical systems. SUBJECTS: Eighteen subjects with
either conductive or mixed hearing loss who could not benefit from conventional
amplification were enrolled in a clinical trial investigating vibratory
stimulation of the round window. INTERVENTION: The floating mass transducer (FMT)
was positioned in the round window niche. MAIN OUTCOME MEASURES: Unaided residual
hearing, and aided sound field thresholds and speech perception abilities were
evaluated preoperatively, and at 1, 3, 6, and 10 months post-activation of the
external speech processor. RESULTS: Six subjects experienced complications that
either required further medical management or resolved on their own. There was no
difference in residual bone conduction thresholds or unaided word discrimination
over time. All subjects experienced a significant improvement in aided speech
perception abilities as compared to preoperative performance. CONCLUSION:
Subjects with conductive and mixed hearing loss with placement of the FMT in the
round window niche experienced improved sound field thresholds and speech
perception, without compromising residual hearing thresholds. Vibratory
stimulation of the round window via a middle ear implant may be an appropriate
treatment option for patients with conductive and mixed hearing loss. Additional
research is needed on the preferred placement of the FMT, improvement of
functional gain, and methods to limit postoperative complications and need for
revision surgery.
PMID- 25111523
TI - The rising incidence of spontaneous cerebrospinal fluid leaks in the United
States and the association with obesity and obstructive sleep apnea.
AB - OBJECTIVE: To determine the national rates of spontaneous CSF leaks and to
determine the association with risk factors. STUDY DESIGN: Retrospective review
from 2002 to 2012. SETTING: University HealthSystem Consortium (UHC) database of
127 of the leading academic medical centers in the United States (81 centers
participated all years of the study). PATIENTS: Those who underwent craniotomy
for CSF leak repair in the UHC database and those who have undergone repair of
spontaneous CSF leaks at one UHC center. INTERVENTION: Assessment of procedure
code rates and patient demographics from 2002 to 2012. MAIN OUTCOME MEASURE:
National rates of craniotomy for spontaneous CSF leak repair each year, the
relation to U.S. regional obesity rates, and the proportion of patients with
coincident obstructive sleep apnea. Spontaneous CSF leak patient characteristics
(age, sex, BMI, hypertension, and OSA) were calculated. RESULTS: The rate of
craniotomy for spontaneous CSF leak repair has risen 2 fold from 2002 (218 cases
per year) to 2012 (488 cases per year). There was no change in the rate of
nonspontaneous CSF leaks over the same period. The rate of spontaneous CSF leak
repair is twice as high (2.54 versus 1.07 per million people per year) in regions
of the United States with the highest obesity rate (Midwest) compared with the
lowest obesity rate (West). All patients with spontaneous CSF leaks were
overweight (BMI, >25 kg/m2) with an average BMI of 37.8 kg/m2. The average age
was 57.03 years, and 72% were female. Patients with spontaneous CSF leaks
presented with high rate of OSA (14.8% nationally and 37.1% at the University of
Iowa) and hypertension (85.7%). CONCLUSION: The national rate of craniotomy for
spontaneous CSF leak repair is rising. This condition is yet another public
health problem related to the rising obesity epidemic. All patients with
spontaneous CSF leaks should be evaluated for OSA.
PMID- 25111524
TI - Intralabyrinthine schwannomas mimic cochleovestibular disease: symptoms from
tumor mass effect in the labyrinth.
AB - OBJECTIVE: To describe symptoms from intralabyrinthine schwannomas specific from
more common vestibular schwannomas of the internal auditory canal or
cerebellopontine angle resulting from mass effect from the tumor within the
labyrinth. PATIENTS: Eight patients diagnosed as having intralabyrinthine
schwannomas from 2000 to 2014 were examined retrospectively from two tertiary
neurotologic centers. INTERVENTIONS: Diagnosis of intralabyrinthine schwannoma
was made with gadolinium-enhanced magnetic resonance imaging scans. Heavily T2
weighted sequences were used to verify mass within the fluid-filled labyrinth.
Patients then underwent audiometric and vestibular testing when appropriate.
Treatment consisted of observation or surgical resection. MAIN OUTCOME MEASURES:
Clinical symptoms, magnetic resonance imaging scans, audiometric and
videonystagmography data, and operative findings were reviewed. RESULTS: Five of
the eight patients had positional vertigo or nystagmus on testing. One patient's
only complaint was positional vertigo without auditory symptoms. Three of the
patients demonstrated mixed hearing loss. Two patients underwent resection of
their tumors, one because of tumor growth and the other because of intractable
vertigo. CONCLUSION: These data show that a high proportion within our series
displayed symptoms of positional vertigo and mixed hearing loss, which are
symptoms not typical of nonintralabyrinthine schwannomas. One patient's only
reported symptom was positional vertigo. These symptoms may arise from the effect
of the tumor's mass exerted on the cochlear and vestibular end organs.
PMID- 25111525
TI - A lightning strike causing a cholesteatoma: a unique form of otologic blast
injury.
AB - OBJECTIVE: We present a case of a middle-aged male struck by lightning while
walking in a parking lot. Assessment of the patient's injuries demonstrated
common sequelae of an otologic blast injury. Review of this case should prepare
the otolaryngologist to identify and manage otologic blast injuries regardless of
their etiology. METHODS: Case study and literature review CASE REPORT: The
patient presented to a level 1 trauma and burn center with a ruptured tympanic
membrane, otalgia, mixed hearing loss, dizziness, and tinnitus. After 3 months of
observation, the patient's tympanic membrane perforation demonstrated little
spontaneous closure. Additionally, he was noted to have formation of a
posttraumatic cholesteatoma in the posterior-superior mesotympanum. Over-under
tympanoplasty with excision of the cholesteatoma was successful, and the
ossicular chain remained intact. The patient underwent vestibular therapy for an
ipsilateral uncompensated vestibular weakness. His dizziness resolved, allowing
him to return to full employment. The patient's final audiogram demonstrated
normal hearing thresholds sloping to a mild mixed hearing loss in the high
frequencies, and the tinnitus reduced significantly in intensity but did not
resolve. CONCLUSION: The patient's injury pattern clearly resulted from the
damaging effects of the shock wave generated by the lightning bolt, which
impacted the patient's thorax. Management of his otologic care was conducted
after practices developed for otologic blast injury and resulted in his being
able to return to his primary occupation.
PMID- 25111526
TI - Power spectral analysis of postural sway during foam posturography in patients
with peripheral vestibular dysfunction.
AB - OBJECTIVE: To assess the frequency-domain characteristics of postural instability
caused by peripheral vestibular dysfunction by performing a power spectral
analysis of the center of pressure (COP) sway during foam posturography. METHODS:
Data were obtained from 78 patients and 163 controls. Two-legged stance tasks
were performed in 4 conditions: eyes open with and without foam rubber, and eyes
closed with and without foam rubber. We estimated the power spectrum of the
acceleration signal using the maximum entropy method. The areas under the curve
(AUCs) of power spectral density of the COP were calculated across low-frequency
(0.02 to 0.1 Hz, LF-AUC), middle-frequency (0.1 to 1Hz, MF-AUC), and high
frequency (1 to 10 Hz, HF-AUC) ranges. We performed binomial logistic regression
analyses to see whether the AUCs of selected bandwidths of COP have a stronger
association with the presence of peripheral vestibular dysfunction in comparison
with the velocity and area in the eyes closed/foam rubber condition. RESULTS: In
both the controls and patients, the MF-AUC was significantly larger than the LF
AUC or HF-AUC in the eyes closed/foam rubber condition. In this condition, the
presence of peripheral vestibular dysfunction had a significantly positive
relationship with MF-AUC and HF-AUC (p < 0.05) and the MF-AUC of the anterior
posterior axis showed a stronger association with the presence of peripheral
vestibular dysfunction than area. CONCLUSION: An increase in activity at middle
frequency movements could be characteristic of peripheral vestibular dysfunction
when standing on foam rubber with the eyes closed.
PMID- 25111527
TI - Genomic medicine for cancer prognosis.
AB - There is a heavy research emphasis on prognostic and predictive approaches based
on genomic data, which has in turn challenged standard paradigms for the
management of patients with malignant disease. This review will highlight the
recent advances made in genomic medicine, specifically with regard to prognosis
associated with thyroid cancer, cutaneous melanoma, and pancreatic
adenocarcinoma. Although none of the markers reviewed have been incorporated into
routine clinical practice, this review covers the most promising ones.
PMID- 25111530
TI - Re: Sarcopenia as a predictor of complications and survival following radical
cystectomy: A. B. Smith, A. M. Deal, H. Yu, B. Boyd, J. Matthews, E. M. Wallen,
R. S. Pruthi, M. E. Woods, H. Muss and M. E. Nielsen. J Urol 2014; 191: 1714
1720.
PMID- 25111531
TI - The sigma-1 receptor agonist 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP)
protects against newborn excitotoxic brain injury by stabilizing the
mitochondrial membrane potential in vitro and inhibiting microglial activation in
vivo.
AB - Premature birth represents a clinical situation of risk for brain injury. The
diversity of pathophysiological processes complicates efforts to find effective
therapeutic strategies. Excitotoxicity is one important factor in the
pathogenesis of preterm brain injury. The observation that sigma-1 receptor
agonists possess neuroprotective potential, at least partly mediated by a variety
of anti-excitotoxic mechanisms, has generated great interest in targeting those
receptors to counteract brain injury. The objective of this study was to evaluate
the effect of the highly specific sigma-1 receptor agonist, 4-phenyl-1-(4
phenylbutyl) piperidine (PPBP) to protect against excitotoxic developmental brain
injury in vivo and in vitro. Primary hippocampal neurons were pre-treated with
PPBP before glutamate was applied and subsequently analyzed for cell death
(PI/calcein AM), mitochondrial activity (TMRM) and morphology of the neuronal
network (WGA) using confocal microscopy. Using an established neonatal mouse
model we also determined whether systemic injection of PPBP significantly
attenuates excitotoxic brain injury. PPBP significantly reduced neuronal cell
death in primary hippocampal neurons exposed to glutamate. Neurons treated with
PPBP showed a less pronounced loss of mitochondrial membrane potential and fewer
morphological changes after glutamate exposure. A single intraperitoneal
injection of PPBP given one hour after the excitotoxic insult significantly
reduced microglial cell activation and lesion size in cortical gray and white
matter. The present study provides strong support for the consideration of sigma
1 receptor agonists as a candidate therapy for the reduction of neonatal
excitotoxic brain lesions and might offer a novel target to counteract
developmental brain injury.
PMID- 25111532
TI - Progressive multiple sclerosis cerebrospinal fluid induces inflammatory
demyelination, axonal loss, and astrogliosis in mice.
AB - Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory
demyelination and neurodegeneration throughout the CNS, which lead over time to a
condition of irreversible functional decline known as progressive MS. Currently,
there are no satisfactory treatments for this condition because the mechanisms
that underlie disease progression are not well understood. This is partly due to
the lack of a specific animal model that represents progressive MS. We
investigated the effects of intracerebroventricular injections of cerebrospinal
fluid (CSF) derived from untreated primary progressive (PPMS), secondary
progressive (SPMS), and relapsing/remitting (RRMS) MS patients into mice. We
found discrete inflammatory demyelinating lesions containing macrophages, B cell
and T cell infiltrates in the brains of animals injected with CSF from patients
with progressive MS. These lesions were rarely found in animals injected with
RRMS-CSF and never in those treated with control-CSF. Animals that developed
brain lesions also presented extensive inflammation in their spinal cord.
However, discrete spinal cord lesions were rare and only seen in animals injected
with PPMS-CSF. Axonal loss and astrogliosis were seen within the lesions
following the initial demyelination. In addition, Th17 cell activity was enhanced
in the CNS and in lymph nodes of progressive MS-CSF injected animals compared to
controls. Furthermore, CSF derived from MS patients who were clinically stable
following therapy had greatly diminished capacity to induce CNS lesions in mice.
Finally, we provided evidence suggesting that differential expression of pro
inflammatory cytokines present in the progressive MS CSF might be involved in the
observed mouse pathology. Our data suggests that the agent(s) responsible for the
demyelination and neurodegeneration characteristic of progressive MS is present
in patient CSF and is amenable to further characterization in experimental models
of the disease.
PMID- 25111533
TI - Mincle signaling in the innate immune response after traumatic brain injury.
AB - The innate immune response contributes to the inflammatory activity after
traumatic brain injury (TBI). In the present study we identify macrophage
inducible C-type lectin (mincle) as a pattern recognition receptor that
contributes to innate immunity in neurons after TBI. Here we report that mincle
is activated by SAP130 in cortical neurons in culture, resulting in production of
the inflammatory cytokine TNF. In addition, mincle and SAP130 are elevated in the
brain and cerebrospinal fluid of humans after TBI and the brain of rodents after
fluid percussion brain injury. Thus, these findings suggest the involvement of
mincle to the pathology of TBI. Importantly, blocking mincle with a neutralizing
antibody against mincle in cortical neurons in culture treated with SAP130
resulted in inhibition of mincle signaling and decreased TNF production.
Therefore, our findings identify mincle as a contributor to the inflammatory
response after TBI.
PMID- 25111534
TI - Graphene-supported Pt and PtPd nanorods with enhanced electrocatalytic
performance for the oxygen reduction reaction.
AB - The combinational modification of the morphology, alloying, and support for Pt
catalysts has been optimized towards the oxygen reduction reaction. Graphene
supported PtPd nanorods have lower unfilled Pt d-states than carbon-supported Pt
nanoparticles (Pt/C) and their specific and mass activities after the accelerated
durability test are about 6.5 and 2.7 times higher than those of Pt/C, attributed
to the synergistic electronic modification effect and graphene-metal interaction.
PMID- 25111536
TI - Tandem mass spectrometry in an electrostatic linear ion trap modified for surface
induced dissociation.
AB - A variety of ion traps are used in mass spectrometry. A key feature shared by
most of them is the ability to perform tandem mass spectrometry (MS/MS). The
Orbitrap is perhaps the most notable ion trap in which MS/MS has yet to be
performed. An electrostatic linear ion trap (ELIT) is analogous to an orbitrap in
that ions are trapped using solely electrostatic fields. However, the relatively
simple ion motion within an ELIT facilitates analysis of fragment ions produced
within the device. In this report, we describe an ELIT to which we have added a
target for surface induced dissociation (SID). When combined with our previously
described method for isolating a precursor ion trapped in an ELIT,1 this
apparatus enables MS/MS to be performed. Measurement of product ion m/z is
facilitated by the fact that the ELIT is isochronous over the energy range of
1850-2000 eV so that changes to ion energy during SID do not cause major m/z
shifts. We demonstrate MS/MS by isolating and dissociating each compound in a
four component mixture of tetraalkylphosphonium cations. We also discuss the
optimization of collision energy and the length of time that the SID target is
available for collision, two parameters that are important in the performance of
these experiments.
PMID- 25111538
TI - Comparison of Quick Track and Melker for emergent invasive airway management
during chest compression: A crossover simulation trial.
PMID- 25111537
TI - Effects of ethanolic dried leaf extract of Lecaniodiscus cupanioides on
antioxidant enzymes and biochemical parameters in rats.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Lecaniodiscus cupanioides is widely used in West
African folk medicine for the treatment of inflammatory conditions, fevers and
bacterial infections. AIM OF THE STUDY: To evaluate the potential toxic effects
of the ethanolic dried leaf extract of Lecaniodiscus cupanioides (LC) on
antioxidant enzymes in selected organs and biochemical parameters. MATERIALS AND
METHODS: Crude ethanolic extract of Lecaniodiscus cupanioides dried leaves was
prepared. A 90-day sub-chronic toxicity study was conducted using albino rats.
Reconstituted Lecaniodiscus cupanioides was administered at a dosage of 400, 800
and 1600 mg/kg (high dose) with a control group receiving 10 ml/kg orally.
Histopathological studies of major organs and blood chemistry analysis were
performed on blood obtained via cardiac puncture after euthanization. Selected
organs (liver, kidney and brain) were harvested for antioxidant and
histopathological assessments. RESULTS: The extract produced significant (p<0.05)
increases in the weights of liver, kidney and brain at 800 mg/kg and 1600 mg/kg
compared to the control. Biochemical analysis showed significant increase in
Alanine transferase (ALT) at 800 mg/kg and 1600 mg/kg. Assay for antioxidant
enzymes showed a reversible decrease in the activity of Catalase (CAT),
Superoxide dismutase (SOD) and Glutathione (GSH) with an increase in
Malondialdehyde (MDA) at 800 mg/kg and 1600 mg/kg Lecaniodiscus cupanioides.
Histopathological study showed reversible congestion in the brain, liver, and
kidney at 800 mg/kg and 1600 mg/kg. CONCLUSION: Findings in this study reveal
that the ethanolic dried leaf extract of Lecaniodiscus cupanioides has the
potential for inhibiting in vivo antioxidant enzymes activity and causing
hepatotoxicity after prolonged exposure.
PMID- 25111539
TI - Electromyographic activity of the diaphragm during neostigmine or sugammadex
enhanced recovery after neuromuscular blockade with rocuronium: a randomised
controlled study in healthy volunteers.
AB - BACKGROUND: The use of neuromuscular blocking agents has been associated with
severe postoperative respiratory morbidity. Complications can be attributed to
inadequate reversal, and reversal agents may themselves have adverse effects.
OBJECTIVE: To compare the electromyographic activity of the diaphragm (EMGdi)
during recovery from neuromuscular blockade using neostigmine and sugammadex. The
hypothesis was that there would be better neuromuscular coupling of the diaphragm
when sugammadex was used. DESIGN: A randomised, controlled, parallel-group,
single-centre, double-blinded study. SETTING: District general hospital in
Belgium. PARTICIPANTS: Twelve healthy male volunteers. INTERVENTIONS: Individuals
were anaesthetised with propofol and remifentanil. After rocuronium 0.6 mg kg, a
transoesophageal electromyography (EMG) recorder was inserted. For reversal of
neuromuscular blockade, volunteers received sugammadex 2 mg kg (n = 6) or
neostigmine 70 MUg kg (n = 6). MAIN OUTCOME MEASURES: EMGdi, airway pressure and
flow were continuously measured during weaning from the ventilator until tracheal
extubation. Arterial blood gas samples were obtained for PaO2 and PaCO2 analysis
at the first spontaneous breathing attempt and after tracheal extubation.
RESULTS: During weaning, 560 breaths were retained for analysis. The median (95%
CI) peak EMGdi was 1.1 (0.9 to 1.5) MUV in the neostigmine group and 1.6 (1.3 to
1.9) MUV in the sugammadex group (P < 0.001). Individuals in the neostigmine
group had 125 of 228 (55%) breaths with associated EMGdi at least 1 MUV vs. 220
of 332 (66%) breaths in the sugammadex group (P = 0.008). The median (95% CI)
tidal volume was 287 (256 to 335) ml after neostigmine and 359 (313 to 398) ml
after sugammadex (P = 0.013). The median (95% CI) PaO2 immediately after
extubation was 30.5 (22.8 to 37.1) kPa after sugammadex vs. 20.7 (12.9 to 27.5)
kPa after neostigmine (P = 0.03). CONCLUSION: EMGdi, tidal volume and PaO2
following tracheal extubation were increased after sugammadex compared with
neostigmine, reflecting diaphragm-driven inspiration after sugammadex
administration. Sugammadex may free more diaphragmatic acetylcholine receptors
than neostigmine, which has an indirect effect. TRIAL REGISTRATION: EudraCT ref:
2013-002078-30.
PMID- 25111540
TI - When visibility hurts and helps: how intersections of race and gender shape Black
professional men's experiences with tokenization.
AB - Research shows groups who experience minority status encounter tokenization. Most
studies applying token theory to minority groups at work focus on either gendered
or racialized processes of tokenization. We offer a different approach by using
an intersectional lens to examine how both race and gender work together to shape
ways Black professional men experience tokenization when employed in
predominantly White male-dominated workplaces. Based on interviews with 42 Black
men employed as doctors, lawyers, bankers, or engineers, we conclude that
although Black professional men encounter some of the typical negative aspects of
tokenization, intersections of race and gender create other important facets that
render their token experience somewhat unique and different from their White
male, White female, and Black female counterparts.
PMID- 25111541
TI - Same spaces, different races: what can cafeteria seating patterns tell us about
intergroup relations in middle school?
AB - Using 2 segregation indices--an exposure index previously used in cafeteria
studies and an entropy index used for the first time, to our knowledge, in this
study--we examined racial segregation in seating patterns among ethnically
diverse middle school students in their school cafeteria over a 2-week period.
Given the representation of groups in the cafeteria each day, results indicated
the expected amount of contact between Asian and White students, but more limited
contact between Asian and Latino students and between White and Latino students.
Latino students, who were in the numerical majority in the sample, appeared least
likely to contribute to overall segregation in the cafeteria. Implications for
using the cafeteria methodology to examine intergroup relations were discussed.
PMID- 25111542
TI - Transracially adoptive parents' color-blind attitudes and views toward
socialization: Cross-racial friendships as a moderator.
AB - This study examined the moderating role of transracially adoptive parents' cross
racial friendships in the relationship between their color-blind attitudes and
views toward cultural and racial socialization. Using hierarchical multiple
regression analyses and the Johnson-Neyman technique, it was hypothesized that
parents' color-blind attitudes would significantly account for 3 different
dimensions of socialization beliefs (i.e., prejudice awareness, ethnic pride, and
egalitarian socialization) and that self-reported cross-racial friendships would
moderate the effects of color-blind attitudes. Results suggest that having
several cross-racial friendships minimized the effects of participants' color
blind attitudes on their ethnic pride and egalitarian socialization beliefs,
whereas having few cross-racial friendships enhanced the effects of color-blind
attitudes on both socialization variables. The importance of transracially
adoptive families creating diverse and multiracial social networks is discussed.
PMID- 25111543
TI - Negotiating multiple marginalizations: experiences of South Asian LGBQ
individuals.
AB - Drawing from minority stress (Meyer, 2003) and feminist multicultural (Brown,
1994) theories, the present study investigated the additive and interactive
relations between 2 types of external minority stress (heterosexist
discrimination and racist events) and 4 internal stress processes related to
identifying as a South Asian American lesbian, gay, bisexual, and queer (LGBQ)
person (internalized heterosexism, acculturation, enculturation, and outness as
LGBQ) with psychological distress. With 142 participants, Pearson's correlations,
multiple regression, and simultaneous multiple moderation analyses were
conducted. Experiences of heterosexist discrimination, racist events, and
internalized heterosexism were correlated positively with psychological distress
and enculturation was correlated negatively. In a test of the additive model,
heterosexist discrimination, racist events, and internalized heterosexism
accounted for significant and unique variance in psychological distress, but
outness, acculturation, and enculturation did not. To test the interactive model,
the simultaneous moderating roles of the internal stress processes were examined
in the links between the external minority stressors to psychological distress.
Only outness as LGBQ emerged as a moderator. The link between racist events and
psychological distress was exacerbated in instances of higher outness, such that
respondents with high racist events and high outness reported the highest levels
of psychological distress. Clinical implications of these findings are discussed
and future research directions focused on the needs of South Asian American LGBQ
people are suggested.
PMID- 25111545
TI - Pedagogy of the Privileged: Review of Deconstructing Privilege: Teaching and
Learning as Allies in the Classroom.
AB - As scholarship and research in multicultural psychology evolves to a multilayered
and complex discipline, increased attention to the role of larger structural
forces of privilege has come to the forefront. Intersectionality of
sociopolitical identities and the role those with privilege have in confronting
oppression becomes a critical component of multicultural education. The edited
volume, Deconstructing Privilege: Teaching and Learning as Allies in the
Classroom (Case, 2013) provides concrete guidance and examples for educators
seeking to enhance their approach to teaching privilege as a necessary mirror of
oppression. This review highlights strengths of the book for educators in
psychology and suggests recommendations for more complex discussion of the
integration of privilege within the framework of structural oppression. (PsycINFO
Database Record (c) 2014 APA, all rights reserved).
PMID- 25111544
TI - Suicidal ideation among racial/ethnic minorities: moderating effects of
rumination and depressive symptoms.
AB - Among emerging adults and college students, racial and ethnic minorities
experience greater risk for suicidal ideation and behavior than their White
counterparts. Research has identified numerous cognitive risk factors for
suicidal ideation. However, they have not been well studied among racial and
ethnic minorities. The present study examined the association between these
factors (brooding rumination, reflective rumination, hopelessness, and depressive
symptoms) and suicidal ideation among 690 Black, Latino, and biracial college
students. Among all groups, hopelessness was positively associated with suicidal
ideation. Brooding was negatively associated with suicidal ideation, after
adjusting for reflection and hopelessness, although only at low levels of
depressive symptoms. Black race/ethnicity and Latino race/ethnicity, compared
with biracial race/ethnicity, each separately interacted with reflection to
predict lower levels of suicidal ideation at moderate to high levels of
reflection. Furthermore, Latino race/ethnicity, compared with biracial
race/ethnicity, interacted with both reflection and depressive symptoms, such
that reflection was negatively associated with suicidal ideation among Latino
individuals reporting depressive symptoms above the 39th percentile. Biracial
race/ethnicity, compared with monoracial race/ethnicity, also interacted with
reflection and depressive symptoms, with reflection associated with greater
amounts of suicidal ideation at depressive symptom levels above the 39th
percentile. Our findings suggest reflective rumination differentially affects
racial and ethnic groups and should be considered in conjunction with depressive
symptoms among Latino and biracial individuals in suicide risk assessment and
treatment.
PMID- 25111546
TI - Perceptions and experiences in higher education: a national study of multiracial
Asian American and Latino/a students in psychology.
AB - Demographic trends suggest increasing numbers of multiple racial heritage
students attending U.S. campuses and universities, a change reflected within
psychology. However, there is little empirical investigation into the educational
experiences and needs of multiracials. The current study (the second in a series
of studies to use data from a national survey of psychology graduate and
undergraduate students) compared 2 multiracial groups, Asian American/European
American and Latino/a/European Americans, with their single-heritage counterparts
on several variables of interest-academic supports and barriers, linkage between
barriers faced and ethnicity, and perceived cultural diversity. Results indicated
that multiracial groups reported more of a link between academic barriers
experienced and their ethnicity than European American students, but less of a
link than their monoracial minority peers. No differences between groups were
found related to academic supports, academic barriers, and perceived cultural
diversity. Study limitations, future research, and implications are discussed.
PMID- 25111547
TI - Ethnicity moderates the outcomes of self-enhancement and self-improvement themes
in expressive writing.
AB - The current study examined whether writing content related to self-enhancing
(viz., downward social comparison and situational attributions) and self
improving (viz., upward social comparison and persistence) motivations were
differentially related to expressive writing outcomes among 17 Asian American and
17 European American participants. Content analysis of the essays revealed no
significant cultural group differences in the likelihood of engaging in self
enhancing versus self-improving reflections on negative personal experiences.
However, cultural group differences were apparent in the relation between self
motivation processes and changes in anxiety and depressive symptoms at 3-month
follow-up. Among European Americans, writing that reflected downward social
comparison predicted positive outcomes, whereas persistence writing themes were
related to poorer outcomes. For Asian Americans, writing about persistence was
related to positive outcomes, whereas downward social comparison and situational
attributions predicted poorer outcomes. Findings provide evidence suggesting
culturally distinct mechanisms for the effects of expressive disclosure.
(PsycINFO Database Record
PMID- 25111548
TI - Cultural distance between parents' and children's creativity: A within-country
approach in Taiwan.
AB - The present study adopted a within-country approach to investigate the relation
of cultural distance to general creativity and math creativity in Taiwan. First,
we conducted a pilot study of 201 young adolescents with parents from one of the
3 largest subethnic groups in Taiwan, namely Min-nan Taiwanese, Ha-kka Taiwanese,
and Outside-Province Taiwanese. The results revealed that young Taiwanese
adolescents perceived the cultural distance between Min-nan Taiwanese and Outside
Province Taiwanese as larger than the cultural distance between the other
subethnic groups. The main study revealed that 610 young adolescents from large
cultural distance families (i.e., those comprising 1 Min-nan Taiwanese parent and
1 Outside-Province Taiwanese parent) outperformed those from small cultural
distance families (i.e., those comprising 2 Min-nan Taiwanese parents, and those
comprising 1 Min-nan Taiwanese parent and 1 Ha-kka Taiwanese parent) on both
general creativity and math creativity. This pattern remained even after
controlling for family socioeconomic status, parents' education level, and
adolescents' school mathematical performance. Implications and limitations are
discussed.
PMID- 25111549
TI - The influence of ethnic group variation on victimization and help seeking among
Latino women.
AB - Interpersonal violence research on Latinos has largely ignored the ethnic group
variations that are included under the pan-ethnic term Latino. The current study
adds to the literature by utilizing a national sample of Latino women to examine
the interpersonal victimization experiences and help-seeking responses to
victimization by ethnic group. The sample was drawn from the Sexual Assault Among
Latinas Study (SALAS; Cuevas & Sabina, 2010) that surveyed 2,000 self-identified
adult Latino women. For the purpose of this study, victimization in the United
States was examined among Mexican ethnics (73.3% of sample), Cuban ethnics (14%),
and other ethnics (12.8%). Mexican ethnicity was found to be significantly
associated with increased odds of experiencing any, physical, sexual, threat, and
stalking victimization. Findings also show that higher levels of Latino
orientation and being an immigrant were associated with decreased odds of
experiencing any victimization, whereas Anglo orientation, as measured by the
Brief ARSMA-II (Cuellar, Arnold, & Maldonado, 1995), was associated with greater
odds of experiencing any victimization. Anglo orientation was significantly
associated with formal help seeking. Taken as a whole, these findings emphasize
the importance of bilingual and culturally competent services and also reveal
that culturally competent services includes developing an understanding of the
cultural differences between Latino ethnic groups. Specifically, service
providers should be aware that Latinos of Mexican ethnicity may face unique risks
for victimization.
PMID- 25111550
TI - Therapist effects, working alliance, and African American women substance users.
AB - African American (AfA) women with substance use disorders experience low rates of
treatment retention compared to other groups of substance abusers. This is
problematic since substance abuse treatment is effective only to the extent
clients are retained. A weak working alliance is a significant barrier to
treatment retention for AfA women. Thus, identifying therapist characteristics
that facilitate a strong working alliance among this population stands as a
promising step toward reducing disparities in treatment retention for this group.
Therapist characteristics were explored as predictors of working alliance with
AfA women substance users (N = 102). Two hypotheses were tested: (1) Population
Sensitive Therapist Characteristics (PSTCs: multicultural competence,
egalitarianism, and empowerment) will explain a significant amount of variance in
working alliance beyond that explained by general therapist characteristics
(GTCs: empathy, regard, and genuineness) and (2) GTCs will partially mediate the
effect of each individual PSTC on working alliance. Hierarchical multiple
regression revealed that PSTCs explained 12% of the variance in working alliance
after controlling for GTCs. Bootstrapping analyses demonstrated that GTCs
mediated the effect of each PSTC on working alliance. Findings suggest that
therapists can facilitate a stronger working alliance with AfA women substance
users through demonstration of PSTCs in addition to GTCs, and that PSTCs are
facilitative because they increase the likelihood the therapist is perceived as
empathic, having unconditional positive regard, and genuine. Clinical and
therapist training implications are discussed.
PMID- 25111551
TI - Person-environment fit: everyday conflict and coparenting conflict in Mexican
origin teen mother families.
AB - The current study examined whether a match or mismatch between teen mothers'
cultural orientation and the cultural context of the family (i.e., familial
ethnic socialization) predicted mother-daughter everyday and coparenting
conflict, and in turn, teen mothers' adjustment. Participants were 204 Mexican
origin teen mothers (M age = 16.81 years; SD = 1.00). Consistent with a person
environment fit perspective, findings indicated that a mismatch between teen
mothers' cultural orientation (i.e., high mainstream cultural involvement) and
the cultural context of the family (i.e., higher levels of familial ethnic
socialization) predicted greater mother-daughter everyday conflict and
coparenting conflict 1 year later. However, when there was a match (i.e., high
levels of familial ethnic socialization for teen mothers with high Mexican
orientation), familial ethnic socialization was not associated with mother
daughter conflict. In addition, mother-daughter conflict was positively
associated with depressive symptoms and engagement in risky behaviors 1 year
later among all teen mothers.
PMID- 25111553
TI - See no evil: color blindness and perceptions of subtle racial discrimination in
the workplace.
AB - Workplace discrimination has grown more ambiguous, with interracial interactions
often perceived differently by different people. The present study adds to the
literature by examining a key individual difference variable in the perception of
discrimination at work, namely individual color-blind attitudes. We examined
relationships between 3 dimensions of color-blind attitudes (Racial Privilege,
Institutional Discrimination, and Blatant Racial Issues) and perceptions of
racial microaggressions in the workplace as enacted by a White supervisor toward
a Black employee (i.e., discriminatory actions ranging from subtle to overt).
Findings showed that observer views on institutional discrimination fully
mediated, and blatant racial issues partially mediated, the relationships between
racial group membership and the perception of workplace microaggressions. Non
Hispanic Whites endorsed color blindness as institutional discrimination and
blatant racial issues significantly more than members of racioethnic minority
groups, and higher levels of color-blind worldviews were associated with lower
likelihoods of perceiving microaggressions. Views on racial privilege did not
differ significantly between members of different racial groups or affect
microaggression perceptions. Implications for organizations concerned about
promoting more inclusive workplaces are discussed.
PMID- 25111552
TI - The joint effect of bias awareness and self-reported prejudice on intergroup
anxiety and intentions for intergroup contact.
AB - Two correlational studies investigated the joint effect of bias awareness-a new
individual difference measure that assesses Whites' awareness and concern about
their propensity to be biased-and prejudice on Whites' intergroup anxiety and
intended intergroup contact. Using a community sample (Study 1), we found the
predicted Bias Awareness * Prejudice interaction. Prejudice was more strongly
related to interracial anxiety among those high (vs. low) in bias awareness.
Study 2 investigated potential behavioral consequences in an important real world
context: medical students' intentions for working primarily with minority
patients. Study 2 replicated the Bias Awareness * Prejudice interaction and
further demonstrated that interracial anxiety mediated medical students'
intentions to work with minority populations.
PMID- 25111554
TI - Mild test anxiety influences neurocognitive performance among African Americans
and European Americans: identifying interfering and facilitating sources.
AB - The current study examined ethnic/racial differences in test-related anxiety and
its relationship to neurocognitive performance in a community sample of African
American (n = 40) and European American (n = 36) adults. The authors hypothesized
the following: (a) Test-anxiety related to negative performance evaluation would
be associated with lower neurocognitive performance, whereas anxiety unrelated to
negative evaluation would be associated with higher neurocognitive performance.
(b) African American participants would report higher levels of anxiety about
negative performance evaluation than European Americans. (c) European Americans
would report higher levels of anxiety unrelated to negative performance
evaluation. The first two hypotheses were supported: Ethnic/racial differences in
test-taking anxiety emerged such that African Americans reported significantly
higher levels of negative performance evaluation, which was associated with lower
cognitive performance. The third hypothesis was not supported: African Americans
and European Americans reported similar levels of test-anxiety unrelated to
negative evaluation.
PMID- 25111555
TI - The Pacific Identity and Wellbeing Scale-Revised (PIWBS-R).
AB - We develop and validate a revised version of the Pacific Identity and Wellbeing
Scale (the PIWBS-R). This revision extends the original 5-factor PIWBS model to
include a sixth subscale assessing Cultural Efficacy (CE). The definition and
item content for CE was based on a synthesis of research on self-efficacy and
Pacific cultural capital. Confirmatory Factor Analysis (N = 919) supported the
revised 6-factor PIWBS-R model. Validation analyses using a sample subset
indicated that the PIWBS-R subscales predicted distinct criterion outcomes (Ns =
452-522). CE uniquely predicted self-reported Church Attendance, travel to the
Pacific Islands, confidence in speaking Pacific heritage language, and
satisfaction with health. Critically, Pacific Connectedness and Belonging and
Perceived Societal Wellbeing predicted a lower likelihood of having been
diagnosed with diabetes. These findings highlight the potential of the PIWBS-R
model for research assessing the protective function of certain aspects of
Pacific identity on health-related outcomes. A copy of the PIWBS-R, scale
psychometrics, and construct definitions are provided.
PMID- 25111556
TI - Mechanistic study on the palladium(II)-catalyzed synthesis of 2,3-disubstituted
indoles under aerobic conditions: anion effects and the development of a low
catalyst-loading process.
AB - As a result of detailed mechanistic and kinetic studies, we have proposed that
PdX2-catalyzed oxidative coupling of o-alkynylanilines 1 with terminal alkynes 2
under aerobic conditions is initiated by aminopalladation of 1 followed by ligand
exchange of the resulting sigma-indolylpalladium(II) complex with 2, reductive
elimination and N-demethylation. Side reactions associated with intermediates on
the way to 2,3-disubstituted indoles 3 were identified, and the roles of acetate
and iodide in channeling the reaction towards the desired product were
established. Based on kinetic and spectroscopic studies, the soluble iodide
ligated Pd(0) species was proposed to be the resting state of the catalyst and
its oxidation to active Pd(II) species was the turnover-limiting step. Catalytic
conditions with low loading of Pd(OAc)2 (0.0005 to 0.001 equiv) were subsequently
developed.
PMID- 25111557
TI - Vibrational dynamics and solvatochromism of the label SCN in various solvents and
hemoglobin by time dependent IR and 2D-IR spectroscopy.
AB - We investigated the characteristics of the thiocyanate (SCN) functional group as
a probe of local structural dynamics for 2D-IR spectroscopy of proteins,
exploiting the dependence of vibrational frequency on the environment of the
label. Steady-state and time-resolved infrared spectroscopy are performed on the
model compound methylthiocyanate (MeSCN) in solvents of different polarity, and
compared to data obtained on SCN as a local probe introduced as cyanylated
cysteine in the protein bovine hemoglobin. The vibrational lifetime of the
protein label is determined to be 37 ps, and its anharmonicity is observed to be
lower than that of the model compound (which itself exhibits solvent-independent
anharmonicity). The vibrational lifetime of MeSCN generally correlates with the
solvent polarity, i.e. longer lifetimes in less polar solvents, with the longest
lifetime being 158 ps. However, the capacity of the solvent to form hydrogen
bonds complicates this simplified picture. The long lifetime of the SCN vibration
is in contrast to commonly used azide labels or isotopically-labeled amide I and
better suited to monitor structural rearrangements by 2D-IR spectroscopy. We
present time-dependent 2D-IR data on the labeled protein which reveal an
initially inhomogeneous structure around the CN oscillator. The distribution
becomes homogeneous after 5 picoseconds so that spectral diffusion has
effectively erased the 'memory' of the CN stretching frequency. Therefore, the 2D
IR data of the label incorporated in hemoglobin demonstrate how SCN can be
utilized to sense rearrangements in the local structure on a picosecond
timescale.
PMID- 25111558
TI - Melasma-like hyperpigmentation induced by intense pulsed light treatment in
Chinese individuals.
AB - BACKGROUND: Symmetric melasma-like hyperpigmentation (MLH) has been identified in
several patients following intense pulsed laser (IPL) treatment sessions. These
patients exhibited no typical signs of melasma prior to IPL therapy. OBJECTIVES:
To investigate the incidence of MLH in Chinese patients receiving IPL treatment
and to discuss potential causative factors for this condition and potential
preventive measures. METHODS: 675 patients with skin types III-IV who were
treated with IPL were retrospectively studied. RESULTS: MLH was noted in 20 cases
(20/675, 2.96%) within 3 months following IPL treatment session. All the patients
had a pigmentary disorder prior to their IPL treatment s, the most common being
photoaging or the presence of freckles. The lesions seen in 14 of the 20 cases
(14/20, 70%) were multiple pigmented lesions along a wide distribution of the
skin with undefined borders. Six of the cases had a strong post-treatment local
reaction which also may have contributed to the MLH. In 2 cases, the original
skin concern became worse following the IPL therapy and may have been a reason
for the formation of MLH. In 6 cases, we noted that these individuals were not
regular users of sunscreen post-therapy, despite our recommendations, which also
may have contributed to the formation of their MLH. CONCLUSIONS: The adverse
event and formation of IPL-induced MLH seen in Chinese individuals does have a
relationship to a primary pigmentary lesion(s) and trend toward melasma prior to
the IPL therapy. The IPL parameters chosen should be suitable for the skin
condition being treated and should follow the recommendations of the
manufacturer's default settings prior to undertaking the treatments. Post-therapy
skin care and the use of appropriate sun protection are also important factors in
preventing MLH.
PMID- 25111559
TI - Palladium-catalyzed direct C(sp(2))-H alkoxylation of 2-aryloxypyridines using 2
pyridyloxyl as the directing group.
AB - An efficient and highly regioselective palladium-catalyzed ortho-C(sp(2))-H bond
alkoxylation of 2-aryloxypyridines was developed using 2-pyridyloxyl as the
directing group and alcohols as alkoxylation reagents. Under an air atmosphere
and in the presence of PhI(OAc)2, the reaction gave the corresponding products in
moderate to good yields, and a series of functional groups could be tolerated.
PMID- 25111560
TI - Gold-catalyzed 1,2-acyloxy migration/intramolecular [3+2] 1,3-dipolar
cycloaddtion cascade reaction: an efficient strategy for syntheses of medium
sized-ring ethers and amines.
AB - A highly efficient strategy for the formation of medium-sized-ring ethers and
amines based on a gold-catalyzed cascade reaction, involving enynyl ester
isomerization and intramolecular [3+2] cyclization, has been developed. Various
multisubstituted medium-sized-ring unsaturated ethers and amines were obtained
through this transformation. This method represents one of the relatively few
transition metal catalyzed intramolecular cycloaddition reactions for medium
sized ring synthesis.
PMID- 25111561
TI - Automatic and quantitative assessment of regional muscle volume by multi-atlas
segmentation using whole-body water-fat MRI.
AB - PURPOSE: To develop and demonstrate a rapid whole-body magnetic resonance imaging
(MRI) method for automatic quantification of total and regional skeletal muscle
volume. MATERIALS AND METHODS: The method was based on a multi-atlas segmentation
of intensity corrected water-fat separated image volumes. Automatic lean muscle
tissue segmentations were achieved by nonrigid registration of atlas datasets
with 10 different manually segmented muscle groups. Ten subjects scanned at 1.5 T
and 3.0 T were used as atlases, initial validation and optimization. Further
validation used 11 subjects scanned at 3.0 T. The automated and manual
segmentations were compared using intraclass correlation, true positive volume
fractions, and delta volumes. RESULTS: For the 1.5 T datasets, the intraclass
correlation, true positive volume fractions (mean +/- standard deviation, SD),
and delta volumes (mean +/- SD) were 0.99, 0.91 +/- 0.02, -0.10 +/- 0.70L (whole
body), 0.99, 0.93 +/- 0.02, 0.01 +/- 0.07L (left anterior thigh), and 0.98, 0.80
+/- 0.07, -0.08 +/- 0.15L (left abdomen). The corresponding values at 3.0 T were
0.97, 0.92 +/- 0.03, -0.17 +/- 1.37L (whole body), 0.99, 0.93 +/- 0.03, 0.03 +/-
0.08L (left anterior thigh), and 0.89, 0.90 +/- 0.04, -0.03 +/- 0.42L (left
abdomen). The validation datasets showed similar results. CONCLUSION: The method
accurately quantified the whole-body skeletal muscle volume and the volume of
separate muscle groups independent of field strength and image resolution.
PMID- 25111562
TI - An arched micro-injector (ARCMI) for innocuous subretinal injection.
AB - Several critical ocular diseases that can lead to blindness are due to retinal
disorders. Subretinal drug delivery has been developed recently for the treatment
of retinal disorders such as hemorrhage because of the specific ocular structure,
namely, the blood retinal barrier (BRB). In the present study, we developed an
Arched Micro-injector (ARCMI) for subretinal drug delivery with minimal retinal
tissue damage. ARCMIs were fabricated using three major techniques: reverse
drawing lithography, controlled air flow, and electroplating. In order to achieve
minimal retinal tissue damage, ARCMIs were fabricated with specific features such
as a 0.15 mm(-1) curvature, 45 degrees tip bevel, 5 mm length, inner diameter of
40 um, and an outer diameter of 100 um. These specific features were optimized
via in-vitro experiments in artificial ocular hemispherical structures and
subretinal injection of indocyanine green in porcine eye ex-vivo. We confirmed
that the ARCMI was capable of delivering ocular drugs by subretinal injection
without unusual subretinal tissue damage, including hemorrhage.
PMID- 25111563
TI - Extracellular matrix components of adipose derived stromal cells promote
alignment, organization, and maturation of cardiomyocytes in vitro.
AB - Adipose derived stromal cells (ADSC) are relevant therapeutic agents to treat
myocardial infarction (MI) in clinical trials. Soluble factors secreted by ADSC,
such as growth factors and cytokines, suppress inflammation and apoptosis while
promoting angiogenesis and the proliferation of cardiomyocytes (CM). Moreover,
ADSC synthesize extracellular matrix (ECM) components into the intercellular
space which might contribute to their therapeutic capacity. Thus, ADSC might
directly modulate the post-MI microenvironment through a combination of paracrine
and juxtacrine signaling. In this study, the juxtacrine role of ADSC and ADSC
derived ECM on the organization and maturation of CM was investiagated. Human
ADSC synthesized and deposited a heterogenous and complex mixture of ECM
components such as collagen I, III, IV, fibronectin, elastin as well as the
matricellular protein periostin. Cocultures of rodent CM with human ADSC or with
human ADSC-derived ECM components enhanced the cardiomyocyte alignment, their
intercellular connections and the maturation of their sarcomeres, while the
proliferation rate of the CM was increased and their level of hypertrophy
reduced. The use of human ADSC-derived ECM could serve both to augment in vitro
tissue-engineered myocardial constructs and to improve myocardial remodeling
after infarction.
PMID- 25111564
TI - Long survival in Leigh syndrome: new cases and review of literature.
AB - Leigh syndrome (MIM 25600), also known as infantile subacute necrotizing
encephalomyelopathy, is a neurodegenerative disorder with characteristic
bilateral symmetric lesions in basal ganglia and subcortical brain regions. It is
commonly associated with systemic cytochrome c oxidase (COX) deficiency and
mutations in the SURF1 gene (MIM 185620), encoding a putative assembly or
maintenance factor of COX. The clinical course is dominated by neurodevelopmental
regression, brain stem, and basal ganglia involvement (e.g., dystonia, apnea)
with death often occurring before the age of 10 years. Herein, we present three
sisters carrying a previously reported homozygous SURF1 mutation (c.868_869insT)
that is predicted to result in a truncated protein with loss of function. Our
patients show heterogeneous clinical findings with different distribution
patterns of metabolic lesions in brain magnetic resonance imaging (MRI) as well
as a Chiari malformation with hydrocephalus in one patient. However, all three
siblings show an unusual long survival (12 years and>16 years). COX activity was
not detectable in one patient and strongly reduced in the other two. We discuss
these findings with respect to a review of the literature. A total of 15
additional patients with survival>14 years have been reported so far. Overall, no
clear genotype-phenotype correlations are detectable among these patients.
PMID- 25111565
TI - Researchers-in-residence: a solution to the challenge of evidence-informed
improvement?
PMID- 25111566
TI - Increased low-frequency oscillation amplitude of sensorimotor cortex associated
with the severity of structural impairment in cervical myelopathy.
AB - Decreases in metabolites and increased motor-related, but decreased sensory
related activation of the sensorimotor cortex (SMC) have been observed in
patients with cervical myelopathy (CM) using advanced MRI techniques. However,
the nature of intrinsic neuronal activity in the SMC, and the relationship
between cerebral function and structural damage of the spinal cord in patients
with CM are not fully understood. The purpose of this study was to assess
intrinsic neuronal activity by calculating the regional amplitude of low
frequency fluctuations (ALFF) using resting-state functional MRI (rs-fMRI), and
correlations with clinical and imaging indices. Nineteen patients and 19 age- and
sex-matched healthy subjects underwent rs-fMRI scans. ALFF measurements were
performed in the SMC, a key brain network likely to impaired or reorganized
patients with CM. Compared with healthy subjects, increased amplitude of cortical
low-frequency oscillations (LFO) was observed in the right precentral gyrus,
right postcentral gyrus, and left supplementary motor area. Furthermore,
increased z-ALFF values in the right precentral gyrus and right postcentral gyrus
correlated with decreased fractional anisotropy values at the C2 level, which
indicated increased intrinsic neuronal activity in the SMC corresponding to the
structural impairment in the spinal cord of patients with CM. These findings
suggest a complex and diverging relationship of cortical functional
reorganization and distal spinal anatomical compression in patients with CM and,
thus, add important information in understanding how spinal cord integrity may be
a factor in the intrinsic covariance of spontaneous low-frequency fluctuations of
BOLD signals involved in cortical plasticity.
PMID- 25111567
TI - Preparation and multiple antitumor properties of AuNRs/spinach extract/PEGDA
composite hydrogel.
AB - In this study, a novel composite hydrogel that contains spinach extract (SE),
gold nanorods (AuNRs), and poly(ethylene glycol) double acrylates (PEGDA) is
prepared through a one-step in situ photopolymerization under noninvasive 660 nm
laser irradiation for localized antitumor activity. SE plays a role as a
photoinitiator for initiating the formation of the PEGDA hydrogel and as an
excellent photosensitizer for generating cytotoxic singlet oxygen ((1)O2) with
oxygen to kill tumor cells. AuNRs can be used as a photoabsorbing agent to
generate heat from optical energy. Moreover, the introduction of AuNRs is
conducive to the formation of the hydrogel and accelerates the rate of (1)O2
generation. The composite hydrogel shell, which has good biocompatibility on
tumor cells, can prevent the photosensitizer from migrating to normal tissue and
maintains a high concentration on lesions, thereby enhancing the curative effect.
The combination of NIR light-triggered mild photothermal heating of AuNRs, the
photodynamic treatment using SE, and localized gelation by photopolymerization
exhibits a synergistic effect for the destruction of cancer cells.
PMID- 25111568
TI - The association of genes involved in the angiogenesis-associated signaling
pathway with risk of anterior cruciate ligament rupture.
AB - Angiogenesis-associated signaling is a fundamental component in the remodeling of
the extracellular matrix in response to loading. Genes encoding protein
components within this signaling cascade are therefore suitable candidates for
investigation into ACL injury susceptibility: namely, vascular endothelial growth
factor A isoform (VEGFA), kinase insert-domain receptor (KDR), nerve growth
factor (NGF), and hypoxia inducible factor-1alpha (HIF1A). A case-control genetic
association study was conducted on 227 asymptomatic control participants and 227
participants with surgically diagnosed ACL ruptures of which 126 participants
reported a non-contact mechanism of rupture. All participants were genotyped for
seven polymorphisms within the four genes. The VEGFA rs699947 CC genotype
(p=0.010, OR: 1.92, 95% CI: 1.17-3.17) was significantly over-represented within
participants with non-contact ACL ruptures. The VEGFA rs1570360 GA genotype was
significantly over-represented in the CON group (p=0.007, OR: 1.70, 95% CI: 1.16
2.50). Furthermore, the KDR rs2071559 GA genotype was significantly over
represented in the female controls (p=0.023, OR: 2.16, 95% CI: 1.11-4.22).
Inferred haplotype analyses also implicated genomic regions spanning the VEGFA
and KDR genes. These novel findings suggest that regions within VEGFA and KDR may
be implicated in the pathophysiology of ACL ruptures; highlighting the potential
biological significance of angiogenesis-associated signaling in the aetiology of
ACL ruptures.
PMID- 25111569
TI - Venous thromboembolism after diaphragm pacing in amyotrophic lateral sclerosis.
AB - INTRODUCTION: Patients with amyotrophic lateral sclerosis (ALS) are prone to
venous thromboembolism (VTE) and secondary complications. Because there is an
increased incidence of VTE after surgical procedures, placement of a Diaphragm
Pacing System (DPS) in ALS patients as treatment for respiratory muscle weakness
could potentially increase the incidence of VTE, especially in patients with
limited mobility. METHODS: We implanted a DPS in 10 ALS patients who met the
criteria for this procedure. They underwent a preoperative evaluation as
recommended by the guidelines. RESULTS: We report 2 patients with no symptoms of
deep vein thrombosis (DVT) before the surgical procedure who then developed
perioperative VTE. CONCLUSIONS: These patients highlight the need to consider
preoperative screening for DVT and postoperative thromboprophylaxis in high-risk
ALS patients who undergo DPS placement.
PMID- 25111570
TI - The combination use of platelet-rich fibrin and treated dentin matrix for tooth
root regeneration by cell homing.
AB - Endogenous regeneration through cell homing provides an alternative approach for
tissue regeneration, except cell transplantation, especially considering clinical
translation. However, tooth root regeneration through cell homing remains a
provocative approach in need of intensive study. Both platelet-rich fibrin (PRF)
and treated dentin matrix (TDM) are warehouses of various growth factors, which
can promote cell homing. We hypothesized that endogenous stem cells are able to
sense biological cues from PRF membrane and TDM, and contribute to the
regeneration of tooth root, including soft and hard periodontal tissues.
Therefore, the biological effects of canine PRF and TDM on periodontal ligament
stem cells (PDLSCs) and bone marrow mesenchymal stem cells (BMSCs) were evaluated
respectively in vitro. Beagle dogs were used as orthotopic transplantation model.
It was found that PRF significantly recruited and stimulated the proliferation of
PDLSCs and BMSCs in vitro. Together, PRF and TDM induced cell differentiation by
upregulating the mineralization-related gene expression of bone sialoprotein
(BSP) and osteopotin (OPN) after 7 days coculture. In vivo, transplantation of
autologous PRF and allogeneic TDM into fresh tooth extraction socket achieved
successful root regeneration 3 months postsurgery, characterized by the
regeneration of cementum and periodontal ligament (PDL)-like tissues with
orientated fibers, indicative of functional restoration. The results suggest that
tooth root connected to the alveolar bone by cementum-PDL complex can be
regenerated through the implantation of PRF and TDM in a tooth socket
microenvironment, probably by homing of BMSCs and PDLSCs. Furthermore, bioactive
cues and inductive microenvironment are key factors for endogenous regeneration.
This approach provides a tangible pathway toward clinical translation.
PMID- 25111571
TI - Mild traumatic brain injury defined by Glasgow Coma Scale: Is it really mild?
AB - INTRODUCTION: Conventionally, a Glasgow Coma Scale (GCS) score of 13-15 defines
mild traumatic brain injury (mTBI). The aim of this study was to identify the
factors that predict progression on repeat head computed tomography (RHCT) and
neurosurgical intervention (NSI) in patients categorized as mild TBI with
intracranial injury (intracranial haemorrhage and/or skull fracture). METHODS:
This study performed a retrospective chart review of all patients with traumatic
brain injury who presented to a level 1 trauma centre. Patients with blunt TBI,
an intracranial injury and admission GCS of 13-15 without anti-platelet and anti
coagulation therapy were included. The outcome measures were: progression on RHCT
and need for neurosurgical intervention (craniotomy and/or craniectomy). RESULTS:
A total of 1800 patients were reviewed, of which 876 patients were included. One
hundred and fifteen (13.1%) patients had progression on RHCT scan. Progression on
RHCT was 8-times more likely in patients with subdural haemorrhage >=10 mm, 5
times more likely with epidural haemorrhage >=10 mm and 3-times more likely with
base deficit >=4. Forty-seven patients underwent a neurosurgical intervention.
Patients with displaced skull fracture were 10-times more likely and patients
with base deficit >4 were 21-times more likely to have a neurosurgical
intervention. CONCLUSION: In patients with intracranial injury, a mild GCS score
(GCS 13-15) in patients with an intracranial injury does not preclude progression
on repeat head CT and the need for a neurosurgical intervention. Base deficit
greater than four and displaced skull fracture are the greatest predictors for
neurosurgical intervention in patients with mild TBI and an intracranial injury.
PMID- 25111572
TI - Synthesizing scientific progress: outcomes from U.S. EPA's carbonaceous aerosols
and source apportionment STAR grants.
AB - In response to recommendations by the National Research Council in the late 1990
s and early 2000s for critical research into understanding sources and formation
mechanisms of PM2.5, EPA created multiple funding opportunities through the
Science to Achieve Results (STAR) program: "Measurement, Modeling, and Analysis
Methods for Airborne Carbonaceous Fine Particulate Matter" (2003) and "Source
Apportionment of Particulate Matter" (2004). The carbonaceous fine PM
solicitation resulted in 16 different projects focusing on the measurement
methods, source identification, and exploration of the chemical and physical
processes important for PM2.5 carbon in the atmosphere. The source apportionment
funding opportunity led to 11 projects improving tools and characterization of
source-receptor relationships of PM2.5. Many funding mechanisms include a final
synopsis of funded research and published manuscripts. Here, this evaluation is
extended to include citations of research published as part of these
solicitations. These solicitations resulted in 275 publications that included
more than 850 unique authors in 37 different journals with a weighted average
2011 impact factor of 4.21. At the time of this assessment, these publications
have been cited by 13,612 peer review journal articles with 31 (11%) of the
manuscripts being cited over 100 times.
PMID- 25111573
TI - Incidence of acute coronary syndrome in the general Medicare population, 1992 to
2009: a real-world perspective.
PMID- 25111574
TI - A review of multiple hypothesis testing in otolaryngology literature.
AB - OBJECTIVES/HYPOTHESIS: Multiple hypothesis testing (or multiple testing) refers
to testing more than one hypothesis within a single analysis, and can inflate the
type I error rate (false positives) within a study. The aim of this review was to
quantify multiple testing in recent large clinical studies in the otolaryngology
literature and to discuss strategies to address this potential problem. DATA
SOURCES: Original clinical research articles with >100 subjects published in 2012
in the four general otolaryngology journals with the highest Journal Citation
Reports 5-year impact factors. REVIEW METHODS: Articles were reviewed to
determine whether the authors tested greater than five hypotheses in at least one
family of inferences. For the articles meeting this criterion for multiple
testing, type I error rates were calculated, and statistical correction was
applied to the reported results. RESULTS: Of the 195 original clinical research
articles reviewed, 72% met the criterion for multiple testing. Within these
studies, there was a mean 41% chance of a type I error and, on average, 18% of
significant results were likely to be false positives. After the Bonferroni
correction was applied, only 57% of significant results reported within the
articles remained significant. CONCLUSIONS: Multiple testing is common in recent
large clinical studies in otolaryngology and deserves closer attention from
researchers, reviewers, and editors. Strategies for adjusting for multiple
testing are discussed.
PMID- 25111575
TI - Safety evaluation of the human-identical milk monosaccharide sialic acid (N
acetyl-d-neuraminic acid) in Sprague-Dawley rats.
AB - N-Acetyl-d-neuraminic acid (Neu5Ac) is the predominant form of sialic acid (Sia)
in humans, while other mammals express Sia as a mixture with N-glycolyl-d
neuraminic acid (Neu5Gc). Neu5Ac occurs in highest levels in the brain and in
breast milk, and is therefore, coined a human-specific milk monosaccharide, and
is thought to play an important nutritional role in the developing infant.
Synthesized human-identical milk monosaccharide (HiMM) Neu5Ac is proposed for use
in infant formulas to better simulate the free saccharides present in human
breast milk. As part of the safety evaluation of HiMM Neu5Ac, a subchronic
dietary toxicity study preceded by an in utero phase was conducted in Sprague
Dawley rats. Neu5Ac was without maternal toxicity or compound-related adverse
effects on female reproduction and on the general growth and development of
offspring at a maternal dietary level of up to 2%, equivalent to a dose of
1895mg/kg body weight (bw)/day. During the subchronic phase, no compound-related
adverse effects were observed in first generation rats at dietary levels of up to
2% (highest level tested), corresponding to doses of 974 and 1246mg/kgbw/day in
males and females, respectively. Neu5Ac also was non-genotoxic in a series of in
vitro genotoxicity/mutagenicity tests. These results support the safe use of
Neu5Ac both in infant formula and as a food ingredient at levels equivalent to
those found naturally in human breast milk.
PMID- 25111578
TI - Stromal nodules in benign prostatic hyperplasia: morphologic and
immunohistochemical characteristics.
AB - BACKGROUND: One hundred forty nine stromal nodules (SNs) from transurethral
resection of benign prostatic hyperplasia specimens in 39 patients (57-85 years
with mean of 70.9) were investigated to characterize the SNs and to outline the
etiopathogenesis of solitary fibrous tumors (SFTs) and gastrointestinal stromal
tumors (GISTs) of prostate by immunohistochemistry performed on tissue microarray
sections. METHODS: Antibodies used included smooth muscle actin, desmin,
vimentin, and S-100 protein for subtyping, vascular endothelial growth factor,
insulin-like growth factor-1, fibroblast growth factor, and TGF-beta as growth
factors; CD133, c-KIT, CD34, and CD44 as stem cell markers; and estrogen (ER),
progesterone (PR), and androgen receptor (AR) as hormone receptors. RESULTS: SNs
were classified into four subtypes: (1) immature mesenchymal (n = 7, 4.7%); (2)
fibroblastic (n = 74, 49.7%); (3) fibromuscular (n = 53, 35.6%); and (4) smooth
muscular (n = 15, 10.1%) types. There were linear trends of the expression of all
growth factors (VEGF, IGF-1, FGF, TGF-beta), but only CD44 stem cell marker and
AR hormone receptor as maturation progressed from immature mesenchymal to smooth
muscular type (Ptrend < 0.05). S-100, c-KIT, and ER were not expressed in any
types of SNs. CD34 was positive in 55% of the SNs (82/149). CONCLUSIONS: The data
suggest that AR and growth factors are important factors for maturation of SNs,
but not influenced by the administration of 5-alpha reductase inhibitor (5ARI).
Although the cells comprising the SNs seem to be not associated with the origin
of prostatic GISTs, there is a possibility of a tentative link of SFTs arising
from SNs of the prostate.
PMID- 25111576
TI - Measures of initiation and progression to increased smoking among current menthol
compared to non-menthol cigarette smokers based on data from four U.S. government
surveys.
AB - There are no large-scale, carefully designed cohort studies that provide evidence
on whether menthol cigarette use is associated with a differential risk of
initiating and/or progressing to increased smoking. However, questions of whether
current menthol cigarette smokers initiated smoking at a younger age or are more
likely to have transitioned from non-daily to daily cigarette use compared to non
menthol smokers can be addressed using cross-sectional data from U.S. government
surveys. Analyses of nationally representative samples of adult and youth smokers
indicate that current menthol cigarette use is not associated with an earlier age
of having initiated smoking or greater likelihood of being a daily versus non
daily smoker. Some surveys likewise provide information on cigarette type
preference (menthol versus non-menthol) among youth at different stages or
trajectories of smoking, based on number of days smoked during the past month
and/or cigarettes smoked per day. Prevalence of menthol cigarette use does not
appear to differ among new, less experienced youth smokers compared to
established youth smokers. While there are limitations with regard to inferences
that can be drawn from cross-sectional analyses, these data do not suggest any
adverse effects for menthol cigarettes on measures of initiation and progression
to increased smoking.
PMID- 25111579
TI - Tissue alterations in urethral and vaginal walls related to multiparity in
rabbits.
AB - In rodents, vaginal distention after delivery or experimental manipulation
affects innervations as well as the amount of striated/smooth musculature or
collagen in both the urethra and vagina. These changes are associated with
modifications in excretory and reproductive processes. Although successive and
consecutive vaginal deliveries (multiparity) affect the contractile and
functional properties of the female lower urogenital tract (LUT), its impact on
LUT morphometry, including persistency, has been barely studied. The caudal
urethra (CU) and cranial (V1) and caudal (V2) pelvic vaginal regions were excised
from young and adult nulliparous (YN and AN, respectively) and multiparous (YM
and AM, respectively) rabbits. Tissues were histologically processed and stained
with Masson's trichrome. The thickness of the tissue layers and areas covered by
tissue components were measured and compared using two-way ANOVA followed by
Student-Newmann-Keuls tests to determine statistical differences (P <= 0.05).
Compared to YN, YM, and AN tissues showed a reduction in the thickness of the
epithelium, as well as in areas covered by striated musculature, collagen, and
blood vessels of the LUT. In comparison with YM, only some morphometric changes
were recovered in the AM group. Our study shows that multiparity and age can be
associated with epithelial and muscular atrophy of urethral and vaginal walls.
The morphometry of the LUT between young and adult female rabbits varies with
multiparity. These findings may help to better understand the effects of
multiparity on young and adult females and its correlation with the development
of pelvic dysfunctions.
PMID- 25111580
TI - Statistical power and optimal design in experiments in which samples of
participants respond to samples of stimuli.
AB - Researchers designing experiments in which a sample of participants responds to a
sample of stimuli are faced with difficult questions about optimal study design.
The conventional procedures of statistical power analysis fail to provide
appropriate answers to these questions because they are based on statistical
models in which stimuli are not assumed to be a source of random variation in the
data, models that are inappropriate for experiments involving crossed random
factors of participants and stimuli. In this article, we present new methods of
power analysis for designs with crossed random factors, and we give detailed,
practical guidance to psychology researchers planning experiments in which a
sample of participants responds to a sample of stimuli. We extensively examine 5
commonly used experimental designs, describe how to estimate statistical power in
each, and provide power analysis results based on a reasonable set of default
parameter values. We then develop general conclusions and formulate rules of
thumb concerning the optimal design of experiments in which a sample of
participants responds to a sample of stimuli. We show that in crossed designs,
statistical power typically does not approach unity as the number of participants
goes to infinity but instead approaches a maximum attainable power value that is
possibly small, depending on the stimulus sample. We also consider the
statistical merits of designs involving multiple stimulus blocks. Finally, we
provide a simple and flexible Web-based power application to aid researchers in
planning studies with samples of stimuli.
PMID- 25111581
TI - Plerixafor and abbreviated-course granulocyte colony-stimulating factor for
mobilizing hematopoietic progenitor cells in light chain amyloidosis.
AB - Cytokine-based mobilization in light chain (AL) amyloidosis is frequently
complicated by fluid overload, weight gain, cardiac arrhythmias, and peri
mobilization mortality. We analyzed hematopoietic progenitor cells (HPC)
mobilization outcomes in 49 consecutive AL amyloidosis patients at our
institution between 2004 and 2013 with granulocyte colony-stimulating factor (G)
(10 MUg/kg/day) (n = 25) versus an institutional protocol to limit G exposure
using plerixafor (P) (.24 mg/kg s.c. starting day 3 of G 10 MUg/kg) (n = 24). G+P
strategy yielded higher total CD34(+) cells/kg (12.8 * 10(6) versus 6.3 * 10(6);
P < .001) and CD34(+) cells/kg collected on day 1 (10.8 * 10(6) versus 4.9 *
10(6), P = .004) compared with the G cohort. More G+P patients collected >=5 *
10(6) CD34(+) HPCs/kg (22 versus 16, P = .02) and >= 10 * 10(6) CD34(+) HPCs/kg
(13 versus 5, P = .01). Four patients (16%) had mobilization failure with G; none
with G+P. Peri-mobilization weight gain was lower with G+P strategy (median
weight gain 1 versus 7 pounds, P = .009). Numbers of apheresis sessions (median,
1 versus 1, P = .52), number of hospitalization days (median, 1.1 versus 1.6, P =
.52), transfusions, use of intravenous antibiotics, and cardiac arrhythmias were
similar. In conclusion, our study demonstrates that upfront use of G+P as a
mobilization strategy results in superior HPC collection, no mobilization
failures, and less weight gain than G alone.
PMID- 25111584
TI - Expression levels of mRNA for neurosteroidogenic enzymes 17beta-HSD, 5alpha
reductase, 3alpha-HSD and cytochrome P450 aromatase in the fetal wild type and SF
1 knockout mouse brain.
AB - The presence of steroidogenic enzymes in the brain suggests de novo synthesis of
steroid hormones in the brain. The current study was designed to determine the
developmental profiles of cytochrome p450 aromatase (cyp19), 17beta
hydroxysteroid dehydrogenase (17beta-HSD), 5alpha-reductase type I and 3alpha
hydroxysteroid dehydrogenase (3alpha-HSD) mRNA expression levels in the fetal
mouse brain and potential influence of peripheral steroids, and the steroidogenic
factor 1 (SF-1) gene on their expression. Brains were collected from WT and SF-1
knockout male and female fetuses at embryonic (E) days E12, E14, E16, and E18.
Quantitative PCR analyses revealed age related increases in the expression levels
of 17beta-HSD and 5alpha-reductase. Differences between genotypes in the
expression levels of 17beta-HSD and 5alpha-reductase were detected on E14, with
reduced levels of expression in SF-1 KO males and females for 17beta-HSD and only
between females for 5alpha-reductase. Expression of 3alpha-HSD mRNA did not
differ significantly between sexes, age groups or genotypes with the exception of
SF-1 KO males, which had an unexplained increase in mRNA for this enzyme on day
E18. Expression of cyp19 was at the limit of detection and could not be analyzed
effectively. There were no sex differences and, with the exception of small
difference on E14 for 17beta-HSD and 5alpha-reductase, no differences between
genotypes. The results suggest that gonadal steroids do not influence the
production of neurosteroids in the fetal brain, nor does SF-1 play a major role
in the regulation of steroidogenic enzyme expression in the brain.
PMID- 25111582
TI - Nonmyeloablative allogeneic hematopoietic stem cell transplantation for GATA2
deficiency.
AB - We treated 14 patients with GATA2 deficiency using a nonmyeloablative allogeneic
hematopoietic stem cell transplantation regimen. Four patients received
peripheral blood stem cells from matched related donors (MRD), 4 patients
received peripheral blood stem cells from matched unrelated donors (URD), 4
patients received hematopoietic stem cells from umbilical cord blood donors
(UCB), and 2 patients received bone marrow cells from haploidentical related
donors. MRD and URD recipients received conditioning with 3 days of fludarabine
and 200 cGy total body irradiation (TBI). Haploidentical related donor recipients
and UCB recipients received cyclophosphamide and 2 additional days of fludarabine
along with 200 cGY TBI. MRD, URD, and UCB recipients received tacrolimus and
sirolimus for post-transplantation immunosuppression, whereas haploidentical
recipients received high-dose cyclophosphamide followed by tacrolimus and
mycophenolate mofetil. Eight patients are alive with reconstitution of the
severely deficient monocyte, B cell, and natural killer cell populations and
reversal of the clinical phenotype at a median follow-up of 3.5 years. Two
patients (1 URD recipient and 1 UCB recipient) rejected the donor graft and 1 MRD
recipient relapsed with myelodysplastic syndrome after transplantation. We are
currently using a high-dose conditioning regimen with busulfan and fludarabine in
patients with GATA2 deficiency to achieve more consistent engraftment and
eradication of the malignant myeloid clones.
PMID- 25111585
TI - Severity of influenza and noninfluenza acute respiratory illness among pregnant
women, 2010-2012.
AB - OBJECTIVE: The objective of the study was to identify characteristics of
influenza illness contrasted with noninfluenza acute respiratory illness (ARI) in
pregnant women. STUDY DESIGN: ARI among pregnant women was identified through
daily surveillance during 2 influenza seasons (2010-2012). Within 8 days of
illness onset, nasopharyngeal swabs were collected, and an interview was
conducted for symptoms and other characteristics. A follow-up telephone interview
was conducted 1-2 weeks later, and medical records were extracted. Severity of
illness was evaluated by self-assessment of 12 illness symptoms, subjective
ratings of overall impairment, highest reported temperature, illness duration,
and medical utilization. RESULTS: Of 292 pregnant women with ARI, 100 tested
positive for influenza viruses. Women with influenza illnesses reported higher
symptom severity than those with noninfluenza ARI (median score, 18 vs 16 of 36;
P < .05) and were more likely to report severe subjective feverishness (18% vs
5%; P < .001), myalgia (28% vs 14%; P < .005), cough (46% vs 30%; P < .01), and
chills (25% vs 13%; P < .01). More influenza illnesses were associated with fever
greater than 38.9 degrees C (20% vs 5%; P < .001) and higher subjective
impairment (mean score, 5.9 vs 4.8; P < .001). Differences in overall symptom
severity, fever, cough, chills, early health care-seeking behavior, and
impairment remained significant in multivariate models after adjusting for study
site, season, age, vaccination status, and number of days since illness onset.
CONCLUSION: Influenza had a greater negative impact on pregnant women than
noninfluenza ARIs, as indicated by symptom severity and greater likelihood of
elevated temperature. These results highlight the importance of preventing and
treating influenza illnesses in pregnant women.
PMID- 25111583
TI - Synergistic cytotoxicity of sorafenib with busulfan and nucleoside analogs in
human FMS-like tyrosine kinase 3 internal tandem duplications-positive acute
myeloid leukemia cells.
AB - Clofarabine (Clo), fludarabine (Flu), and busulfan (Bu) are used in
pretransplantation conditioning therapy for patients with myeloid leukemia. To
further improve their efficacy in FMS-like tyrosine kinase 3 internal tandem
duplications (FLT3-ITD)-positive acute myeloid leukemia (AML), we investigated
their synergism with sorafenib (Sor). Exposure of FLT3-ITD-positive MV-4-11 and
MOLM 13 cells to Bu+Clo+Flu+Sor resulted in synergistic cytotoxicity; no such
synergism was observed in the FLT3-wild type THP-1 and KBM3/Bu250(6) cell lines.
The drug synergism in MV-4-11 cells could be attributed to activation of DNA
damage response, histone 3 modifications, inhibition of prosurvival kinases, and
activation of apoptosis. Further, the phosphorylation of kinases, including FLT3,
MAPK kinase (MEK), and AKT, was inhibited. The FLT3-ITD substrate STAT5 and its
target gene PIM 2 product decreased when cells were exposed to Sor alone,
Bu+Clo+Flu, and Bu+Clo+Flu+Sor. The level of the proapoptotic protein p53
upregulated modulator of apoptosis (PUMA) increased, whereas the level of
prosurvival protein MCL-1 decreased when cells were exposed to Bu+Clo+Flu+Sor.
The interactions of PUMA with MCL-1 and/or BCL-2 were enhanced when cells were
exposed to Bu+Clo+Flu or Bu+Clo+Flu+Sor. The changes in the level of these
proteins, which are involved in mitochondrial control of apoptosis, correlate
with changes in mitochondrial membrane potential. Bu+Clo+Flu+Sor decreased
mitochondrial membrane potential by 60% and caused leakage of cytochrome c,
second mitochondria-derived activator of caspases (SMAC)/direct IAP Binding
protein with low pI (DIABLO), and AIF from the mitochondria to the cytoplasm,
caspase activation, and cell death, suggesting the activation of apoptosis.
Analogous, synergistic cytotoxicity in response to Bu, Clo, Flu, and Sor was
observed in mononuclear cells isolated from FLT3-ITD-positive AML patients.
Although our previous studies were aimed at standardizing the conditioning
regimen, the new findings suggest that patients with abnormal expression of FLT3
might further benefit from individualizing treatment through the addition of Sor
to Bu+Clo+Flu, thereby providing personalized pretransplantation therapy.
PMID- 25111586
TI - Repeated measures of urinary oxidative stress biomarkers during pregnancy and
preterm birth.
AB - OBJECTIVE: The purpose of this study was to investigate oxidative stress as a
mechanism of preterm birth in human subjects; we examined associations between
urinary biomarkers of oxidative stress that were measured at multiple time points
during pregnancy and preterm birth. STUDY DESIGN: This nested case-control study
included 130 mothers who delivered preterm and 352 mothers who delivered term who
were originally recruited as part of an ongoing prospective birth cohort at
Brigham and Women's Hospital. Two biomarkers that included 8
hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane were measured in urine samples
that were collected at up to 4 time points (median 10, 18, 26, and 35 weeks)
during gestation. RESULTS: Urinary concentrations of 8-isoprostane and 8-OHdG
decreased and increased, respectively, as pregnancy progressed. Average levels of
8-isoprostane across pregnancy were associated with increased odds of spontaneous
preterm birth (adjusted odds ratio, 6.25; 95% confidence interval, 2.86-13.7),
and associations were strongest with levels measured later in pregnancy. Average
levels of 8-OHdG were protective against overall preterm birth (adjusted odds
ratio, 0.19; 95% confidence interval, 0.10-0.34), and there were no apparent
differences in the protective effect in cases of spontaneous preterm birth
compared with cases of placental origin. Odds ratios for overall preterm birth
were more protective in association with urinary 8-OHdG concentrations that were
measured early in pregnancy. CONCLUSION: Maternal oxidative stress may be an
important contributor to preterm birth, regardless of subtype and timing of
exposure during pregnancy. The 2 biomarkers that were measured in the present
study had opposite associations with preterm birth; an improved understanding of
what each represents may help to identify more precisely important mechanisms in
the pathway to preterm birth.
PMID- 25111587
TI - Clinical experience and follow-up with large scale single-nucleotide polymorphism
based noninvasive prenatal aneuploidy testing.
AB - OBJECTIVE: We sought to report on laboratory and clinical experience following 6
months of clinical implementation of a single-nucleotide polymorphism-based
noninvasive prenatal aneuploidy test in high- and low-risk women. STUDY DESIGN:
All samples received from March through September 2013 and drawn >=9 weeks'
gestation were included. Samples that passed quality control were analyzed for
trisomy 21, trisomy 18, trisomy 13, and monosomy X. Results were reported as high
or low risk for fetal aneuploidy for each interrogated chromosome. Relationships
between fetal fraction and gestational age and maternal weight were analyzed.
Follow-up on outcome was sought for a subset of high-risk cases. False-negative
results were reported voluntarily by providers. Positive predictive value (PPV)
was calculated from cases with an available prenatal or postnatal karyotype or
clinical evaluation at birth. RESULTS: Samples were received from 31,030
patients, 30,705 met study criteria, and 28,739 passed quality-control metrics
and received a report detailing aneuploidy risk. Fetal fraction correlated
positively with gestational age, and negatively with maternal weight. In all, 507
patients received a high-risk result for any of the 4 tested conditions (324
trisomy 21, 82 trisomy 18, 41 trisomy 13, 61 monosomy X; including 1 double
aneuploidy case). Within the 17,885 cases included in follow-up analysis, 356
were high risk, and outcome information revealed 184 (51.7%) true positives, 38
(10.7%) false positives, 19 (5.3%) with ultrasound findings suggestive of
aneuploidy, 36 (10.1%) spontaneous abortions without karyotype confirmation, 22
(6.2%) terminations without karyotype confirmation, and 57 (16.0%) lost to follow
up. This yielded an 82.9% PPV for all aneuploidies, and a 90.9% PPV for trisomy
21. The overall PPV for women aged >=35 years was similar to the PPV for women
aged <35 years. Two patients were reported as false negatives. CONCLUSION: The
data from this large-scale report on clinical application of a commercially
available noninvasive prenatal test suggest that the clinical performance of this
single-nucleotide polymorphism-based noninvasive prenatal test in a mixed high-
and low-risk population is consistent with performance in validation studies.
PMID- 25111589
TI - The structure of cyclolinopeptide A in chloroform refined by RDC measurements.
AB - Three-dimensional structures of molecules traditionally assigned from nuclear
Overhauser effects and vicinal coupling constants are recently complemented by
measurements of residual dipolar couplings. Residual dipolar couplings measured
in a stretched poly(dimethylsiloxane) gel were used to determine the structure of
cyclolinopeptide A in chloroform solution at -50 degrees C. After structure
refinement, conformational details of main cluster were discussed in relation to
crystal and nuclear Overhauser effect derived structures.
PMID- 25111590
TI - Probing the electronic properties of individual MnPc molecules coupled to
topological states.
AB - Hybrid organic/inorganic interfaces have been widely reported to host emergent
properties that go beyond those of their single constituents. Coupling molecules
to the recently discovered topological insulators, which possess linearly
dispersing and spin-momentum-locked Dirac fermions, may offer a promising
platform toward new functionalities. Here, we report a scanning tunneling
microscopy and spectroscopy study of the prototypical interface between MnPc
molecules and a Bi2Te3 surface. MnPc is found to bind stably to the substrate
through its central Mn atom. The adsorption process is only accompanied by a
minor charge transfer across the interface, resulting in a moderately n-doped
Bi2Te3 surface. More remarkably, topological states remain completely unaffected
by the presence of the molecules, as evidenced by the absence of scattering
patterns around adsorption sites. Interestingly, we show that, while the HOMO and
LUMO orbitals closely resemble those of MnPc in the gas phase, a new hybrid state
emerges through interaction with the substrate. Our results pave the way toward
hybrid organic-topological insulator heterostructures, which may unveil a broad
range of exciting and unknown phenomena.
PMID- 25111591
TI - Cellular immune responses against viral pathogens in shrimp.
AB - Shrimp is one of the most important commercial marine species worldwide; however,
viral diseases threaten the healthy development of shrimp aquaculture. In order
to develop efficient control strategies against viral diseases, researchers have
begun focusing increasing attention to the molecular mechanism of shrimp innate
immunity. Although knowledge of shrimp humoral immunity has grown significantly
in recent years, very little information is available about the cell-mediated
immune responses. Several cellular processes such as phagocytosis, apoptosis, and
RNA interference critical in cellular immune response play a significant role in
endogenous antiviral activity in shrimp. In this review, we summarize the
emerging research and highlight key mediators of cellular immune response to
viral pathogens.
PMID- 25111592
TI - A rapid and label-free SERS detection method for biomarkers in clinical
biofluids.
AB - A metal carbonyl-functionalized nanostructured substrate can be used in a rapid
and simple assay for the detection of A1AT, a potential biomarker for bladder
cancer, in clinical urine samples. The assay involves monitoring changes in the
carbonyl stretching vibrations of the metal carbonyl via surface-enhanced Raman
spectroscopy (SERS). These vibrations lie in the absorption spectral window of
1800-2200 cm(-1), which is free of any spectral interference from biomolecules.
PMID- 25111588
TI - Systematic review and metaanalysis of genetic association studies of urinary
symptoms and prolapse in women.
AB - OBJECTIVE: Family studies and twin studies demonstrate that lower urinary tract
symptoms and pelvic organ prolapse are heritable. This review aimed to identify
genetic polymorphisms tested for an association with lower urinary tract symptoms
or prolapse, and to assess the strength, consistency, and risk of bias among
reported associations. STUDY DESIGN: PubMed and HuGE Navigator were searched up
to May 1, 2014, using a combination of genetic and phenotype key words, including
"nocturia," "incontinence," "overactive bladder," "prolapse," and "enuresis."
Major genetics, urology, and gynecology conference abstracts were searched from
2005 through 2013. We screened 889 abstracts, and retrieved 78 full texts. In
all, 27 published and 7 unpublished studies provided data on polymorphisms in or
near 32 different genes. Fixed and random effects metaanalyses were conducted
using codominant models of inheritance. We assessed the credibility of pooled
associations using the interim Venice criteria. RESULTS: In pooled analysis, the
rs4994 polymorphism of the ADRB3 gene was associated with overactive bladder
(odds ratio [OR], 2.5; 95% confidence interval [CI], 1.7-3.6; n = 419). The
rs1800012 polymorphism of the COL1A1 gene was associated with prolapse (OR, 1.3;
95% CI, 1.0-1.7; n = 838) and stress urinary incontinence (OR, 2.1; 95% CI, 1.4
3.2; n = 190). Other metaanalyses, including those for polymorphisms of
COL3A1,LAMC1,MMP1,MMP3, and MMP9 did not show significant effects. Many studies
were at high risk of bias from genotyping error or population stratification.
CONCLUSION: These metaanalyses provide moderate epidemiological credibility for
associations of variation in ADRB3 with overactive bladder, and variation of
COL1A1 with prolapse. Clinical testing for any of these polymorphisms cannot be
recommended based on current evidence.
PMID- 25111593
TI - Role of troponin in patients with chronic kidney disease and suspected acute
coronary syndrome: a systematic review.
AB - BACKGROUND: Patients with chronic kidney disease (CKD) have high prevalence of
elevated serum troponin levels, which makes diagnosis of acute coronary syndrome
(ACS) challenging. PURPOSE: To evaluate the utility of troponin in ACS diagnosis,
treatment, and prognosis among patients with CKD. DATA SOURCES: MEDLINE, EMBASE,
and the Cochrane Central Register of Controlled Trials through May 2014. STUDY
SELECTION: Studies examining elevated versus normal troponin levels in terms of
their diagnostic performance in detection of ACS, effect on ACS management
strategies, and prognostic value for mortality or cardiovascular events after ACS
among patients with CKD. DATA EXTRACTION: Paired reviewers selected articles for
inclusion, extracted data, and graded strength of evidence (SOE). DATA SYNTHESIS:
Twenty-three studies met inclusion criteria. The sensitivity of troponin T for
ACS diagnosis ranged from 71% to 100%, and specificity ranged from 31% to 86% (6
studies; low SOE). The sensitivity and specificity of troponin I ranged from 43%
to 94% and from 48% to 100%, respectively (8 studies; low SOE). No studies
examined how troponin levels affect management strategies. Twelve studies
analyzed prognostic value. Elevated levels of troponin I or troponin T were
associated with higher risk for short-term death and cardiac events (low SOE). A
similar trend was observed for long-term mortality with troponin I (low SOE), but
less evidence was found for long-term cardiac events for troponin I and long-term
outcomes for troponin T (insufficient SOE). Patients with advanced CKD tended to
have worse prognoses with elevated troponin I levels than those without them
(moderate SOE). LIMITATION: Studies were heterogeneous in design and in ACS
definitions and adjudication methods. CONCLUSION: In patients with CKD and
suspected ACS, troponin levels can aid in identifying those with a poor
prognosis, but the diagnostic utility is limited by varying estimates of
sensitivity and specificity. PRIMARY FUNDING SOURCE: Agency for Healthcare
Research and Quality.
PMID- 25111594
TI - Circulating tumour cells in metastatic head and neck cancers.
AB - Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer
with 650,000 new cases p/a worldwide. HNSCC causes high morbidity with a 5-year
survival rate of less than 60%, which has not improved due to the lack of early
detection (Bozec et al. Eur Arch Otorhinolaryngol. 2013;270: 2745-9). Metastatic
disease remains one of the leading causes of death in HNSCC patients. This review
article provides a comprehensive overview of literature over the past 5 years on
the detection of circulating tumour cells (CTCs) in HNSCC; CTC biology and future
perspectives. CTCs are a hallmark of invasive cancer cells and key to metastasis.
CTCs can be used as surrogate markers of overall survival and progression-free
survival. CTCs are currently used as prognostic factors for breast, prostate and
colorectal cancers using the CellSearch(r) system. CTCs have been detected in
HNSCC, however, these numbers depend on the technique applied, time of blood
collection and the clinical stage of the patient. The impact of CTCs in HNSCC is
not well understood, and thus, not in routine clinical practice. Validated
detection technologies that are able to capture CTCs undergoing epithelial
mesenchymal transition are needed. This will aid in the capture of heterogeneous
CTCs, which can be compiled as new targets for the current food and drug
administration-cleared CellSearch(r) system. Recent studies on CTCs in HNSCC with
the CellSearch(r) have shown variable data. Therefore, there is an immediate need
for large clinical trials encompassing a suite of biomarkers capturing CTCs in
HNSCC, before CTCs can be used as prognostic markers in HNSCC patient management.
PMID- 25111595
TI - Expression of heat shock protein 47, transforming growth factor-beta 1, and
connective tissue growth factor in liver tissue of patients with Schistosoma
japonicum-induced hepatic fibrosis.
AB - SUMMARY To detect the expression of pro-fibrotic molecules, such as heat shock
protein 47 (Hsp47), transforming growth factor-beta 1 (TGF-beta1) and connective
tissue growth factor (CTGF) in liver specimens, and analyse their correlations
with the progression of schistosomal hepatic fibrosis, liver biopsy was performed
in 42 chronic schistosomiasis (CS) patients, 16 chronic hepatitis B (CHB)
patients and five healthy individuals (HI). Immunohistochemistry (IHC) analyses
displayed that the expression of Hsp47, TGF-beta1 and CTGF was increased in CS
and CHB patients compared with HI. Using real-time PCR, the mRNA levels of Hsp47,
TGF-beta1 and CTGF were higher in CS patients compared with HI. In CS patients,
the mRNA levels of these genes were correlated with the stage of fibrosis, and
TGF-beta1 mRNA expression was associated with the grade of inflammation.
Additional analyses indicated that the mRNA levels of Hsp47 and CTGF were highly
correlated with liver stiffness value and spleen thickness diameter, both of
which represented the severity of fibrosis. In conclusion, the three molecules
are involved in the pathogenesis of hepatic fibrosis infected by Schistosoma
japonicum. TGF-beta1 participates not only in the inflammatory process, but also
in the fibrotic process in which Hsp47 and CTGF probably play a key role.
PMID- 25111596
TI - Contaminants of emerging concern in fresh leachate from landfills in the
conterminous United States.
AB - To better understand the composition of contaminants of emerging concern (CECs)
in landfill leachate, fresh leachate from 19 landfills was sampled across the
United States during 2011. The sampled network included 12 municipal and 7
private landfills with varying landfill waste compositions, geographic and
climatic settings, ages of waste, waste loads, and leachate production. A total
of 129 out of 202 CECs were detected during this study, including 62 prescription
pharmaceuticals, 23 industrial chemicals, 18 nonprescription pharmaceuticals, 16
household chemicals, 6 steroid hormones, and 4 plant/animal sterols. CECs were
detected in every leachate sample, with the total number of detected CECs in
samples ranging from 6 to 82 (median = 31). Bisphenol A (BPA), cotinine, and N,N
diethyltoluamide (DEET) were the most frequently detected CECs, being found in
95% of the leachate samples, followed by lidocaine (89%) and camphor (84%). Other
frequently detected CECs included benzophenone, naphthalene, and amphetamine,
each detected in 79% of the leachate samples. CEC concentrations spanned six
orders of magnitude, ranging from ng L(-1) to mg L(-1). Industrial and household
chemicals were measured in the greatest concentrations, composing more than 82%
of the total measured CEC concentrations. Maximum concentrations for three
household and industrial chemicals, para-cresol (7 020 000 ng L(-1)), BPA (6 380
000 ng L(-1)), and phenol (1 550 000 ng L(-1)), were the largest measured, with
these CECs composing 70% of the total measured CEC concentrations.
Nonprescription pharmaceuticals represented 12%, plant/animal sterols 4%,
prescription pharmaceuticals 1%, and steroid hormones <1% of the total measured
CEC concentrations. Leachate from landfills in areas receiving greater amounts of
precipitation had greater frequencies of CEC detections and concentrations in
leachate than landfills receiving less precipitation.
PMID- 25111597
TI - Polycystic kidney disease with steatocystoma multiplex: evidences for a
disruptive effect of mutated polycystin-1 on keratin 17 polymerisation.
PMID- 25111598
TI - Exploring three PIPs and three TIPs of grapevine for transport of water and
atypical substrates through heterologous expression in aqy-null yeast.
AB - Aquaporins are membrane channels that facilitate the transport of water and other
small molecules across the cellular membranes. We examined the role of six
aquaporins of Vitis vinifera (cv. Touriga nacional) in the transport of water and
atypical substrates (other than water) in an aqy-null strain of Saccharomyces
cerevisiae. Their functional characterization for water transport was performed
by stopped-flow fluorescence spectroscopy. The evaluation of permeability
coefficients (Pf) and activation energies (Ea) revealed that three aquaporins
(VvTnPIP2;1, VvTnTIP1;1 and VvTnTIP2;2) are functional for water transport, while
the other three (VvTnPIP1;4, VvTnPIP2;3 and VvTnTIP4;1) are non-functional. TIPs
(VvTnTIP1;1 and VvTnTIP2;2) exhibited higher water permeability than VvTnPIP2;1.
All functional aquaporins were found to be sensitive to HgCl2, since their water
conductivity was reduced (24-38%) by the addition of 0.5 mM HgCl2. Expression of
Vitis aquaporins caused different sensitive phenotypes to yeast strains when
grown under hyperosmotic stress generated by KCl or sorbitol. Our results also
indicate that Vitis aquaporins are putative transporters of other small molecules
of physiological importance. Their sequence analyses revealed the presence of
signature sequences for transport of ammonia, boron, CO2, H2O2 and urea. The
phenotypic growth variations of yeast cells showed that heterologous expression
of Vitis aquaporins increased susceptibility to externally applied boron and
H2O2, suggesting the contribution of Vitis aquaporins in the transport of these
species.
PMID- 25111599
TI - Atomic force microscopy reveals a morphological differentiation of
chromobacterium violaceum cells associated with biofilm development and directed
by N-hexanoyl-L-homoserine lactone.
AB - Chromobacterium violaceum abounds in soil and water ecosystems in tropical and
subtropical regions and occasionally causes severe and often fatal human and
animal infections. The quorum sensing (QS) system and biofilm formation are
essential for C. violaceum's adaptability and pathogenicity, however, their
interrelation is still unknown. C. violaceum's cell and biofilm morphology were
examined by atomic force microscopy (AFM) in comparison with growth rates, QS
dependent violacein biosynthesis and biofilm biomass quantification. To evaluate
QS regulation of these processes, the wild-type strain C. violaceum ATCC 31532
and its mini-Tn5 mutant C. violaceum NCTC 13274, cultivated with and without the
QS autoinducer N-hexanoyl-L-homoserine lactone (C6-HSL), were used. We report for
the first time the unusual morphological differentiation of C. violaceum cells,
associated with biofilm development and directed by the QS autoinducer. AFM
revealed numerous invaginations of the external cytoplasmic membrane of wild-type
cells, which were repressed in the mutant strain and restored by exogenous C6
HSL. With increasing bacterial growth, polymer matrix extrusions formed in place
of invaginations, whereas mutant cells were covered with a diffusely distributed
extracellular substance. Thus, quorum sensing in C. violaceum involves a
morphological differentiation that organises biofilm formation and leads to a
highly differentiated matrix structure.
PMID- 25111600
TI - Mating behavior of Daphnia: impacts of predation risk, food quantity, and
reproductive phase of females.
AB - High predation risk and food depletion lead to sexual reproduction in cyclically
parthenogenetic Daphnia. Mating, the core of sexual reproduction, also occurs
under these conditions. Assessment of the environmental conditions and alteration
of mating efforts may aid in determining the success of sexual reproduction.
Here, we evaluated the impacts of predation risk, food quantity, and reproductive
phase of females on the mating behavior of Daphnia obtusa males including contact
frequency and duration using video analysis. Mating-related behavior involved
male-female contact (mating) as well as male-male contact (fighting). Mating
frequency increased while unnecessary fighting decreased in the presence of
predation risk. In addition, low food concentration reduced fighting between
males. Males attempted to attach to sexual females more than asexual females, and
fighting occurred more frequently in the presence of sexual females. Duration of
mating was relatively long; however, males separated shortly after contact in
terms of fighting behavior. Thus, assessment of environmental factors and primary
sexing of mates were performed before actual contact, possibly mechanically, and
precise sex discrimination was conducted after contact. These results suggest
that mating in Daphnia is not a random process but rather a balance between
predation risk and energetic cost that results in changes in mating and fighting
strategies.
PMID- 25111601
TI - Pentameric thiophene-based ligands that spectrally discriminate amyloid-beta and
tau aggregates display distinct solvatochromism and viscosity-induced spectral
shifts.
AB - A wide range of neurodegenerative diseases are characterized by the deposition of
multiple protein aggregates. Ligands for molecular characterization and
discrimination of these pathological hallmarks are thus important for
understanding their potential role in pathogenesis as well as for clinical
diagnosis of the disease. In this regard, luminescent conjugated oligothiophenes
(LCOs) have proven useful for spectral discrimination of amyloid-beta (Abeta) and
tau neurofibrillary tangles (NFTs), two of the pathological hallmarks associated
with Alzheimer's disease. Herein, the solvatochromism of a library of anionic
pentameric thiophene-based ligands, as well as their ability to spectrally
discriminate Abeta and tau aggregates, were investigated. Overall, the results
from this study identified distinct solvatochromic and viscosity-dependent
behavior of thiophene-based ligands that can be applied as indices to direct the
chemical design of improved LCOs for spectral separation of Abeta and tau
aggregates in brain tissue sections. The results also suggest that the observed
spectral transitions of the ligands are due to their ability to conform by
induced fit to specific microenvironments within the binding interface of each
particular protein aggregate. We foresee that these findings might aid in the
chemical design of thiophene-based ligands that are increasingly selective for
distinct disease-associated protein aggregates.
PMID- 25111604
TI - Diagnosis, mechanisms and treatment of complex regional pain syndrome.
AB - PURPOSE OF REVIEW: The incidence and disease course of complex regional pain
syndrome (CRPS) has been unclear until recently. This was due to inconsistent
diagnostic criteria used in previous studies and a lack of large-scale
prospective datasets. Multiple mechanisms of CRPS have been suggested, and recent
research has begun to explain how inflammation, the immune system and the
autonomic nervous system may interact with aberrant central neuroplasticity to
produce the clinical picture. This review summarizes progress in these fields.
RECENT FINDINGS: National registries of patients with CRPS have provided us with
an invaluable insight into the epidemiology of the disorder. We now have a better
understanding of the disease course and expected outcome. Widespread sensory
abnormalities, not limited to the CRPS limb, have been found suggesting that
systemic changes may occur. Parietal lobe dysfunction and problems with sensory
motor integration have also been revealed. Abnormalities in the immune system in
CRPS have also been demonstrated. SUMMARY: Recent findings in diverse research
fields suggest novel treatment options for CRPS: from targeting autoimmunity to
correcting abnormal body image. Many of the advances in our understanding of CRPS
have arisen from the development of collaborative research efforts, such as the
TREND group in the Netherlands.
PMID- 25111602
TI - Abnormal mitochondrial L-arginine transport contributes to the pathogenesis of
heart failure and rexoygenation injury.
AB - BACKGROUND: Impaired mitochondrial function is fundamental feature of heart
failure (HF) and myocardial ischemia. In addition to the effects of heightened
oxidative stress, altered nitric oxide (NO) metabolism, generated by a
mitochondrial NO synthase, has also been proposed to impact upon mitochondrial
function. However, the mechanism responsible for arginine transport into
mitochondria and the effect of HF on such a process is unknown. We therefore
aimed to characterize mitochondrial L-arginine transport and to investigate the
hypothesis that impaired mitochondrial L-arginine transport plays a key role in
the pathogenesis of heart failure and myocardial injury. METHODS AND RESULTS: In
mitochondria isolated from failing hearts (sheep rapid pacing model and mouse
Mst1 transgenic model) we demonstrated a marked reduction in L-arginine uptake
(p<0.05 and p<0.01 respectively) and expression of the principal L-arginine
transporter, CAT-1 (p<0.001, p<0.01) compared to controls. This was accompanied
by significantly lower NO production and higher 3-nitrotyrosine levels (both
p<0.05). The role of mitochondrial L-arginine transport in modulating cardiac
stress responses was examined in cardiomyocytes with mitochondrial specific
overexpression of CAT-1 (mtCAT1) exposed to hypoxia-reoxygenation stress. mtCAT1
cardiomyocytes had significantly improved mitochondrial membrane potential,
respiration and ATP turnover together with significantly decreased reactive
oxygen species production and cell death following mitochondrial stress.
CONCLUSION: These data provide new insights into the role of L-arginine transport
in mitochondrial biology and cardiovascular disease. Augmentation of
mitochondrial L-arginine availability may be a novel therapeutic strategy for
myocardial disorders involving mitochondrial stress such as heart failure and
reperfusion injury.
PMID- 25111605
TI - Regional analgesia techniques for total knee replacement.
AB - PURPOSE OF REVIEW: Pain following total knee arthroplasty is a challenging task
for healthcare providers. Concurrently, fast recovery and early ambulation are
required to regain function and to prevent postoperative complications. Ideal
postoperative analgesia provides sufficient pain relief with minimal opioid
consumption and preservation of motor strength. Regional analgesia techniques are
broadly used to answer these expectations. Femoral nerve blocks are performed
frequently but have suggested disadvantages, such as motor weakness. The use of
lumbar epidurals is questioned because of the risk of epidural hematoma.
Relatively new techniques, such as local infiltration analgesia or adductor canal
blocks, are increasingly discussed. The present review discusses new findings and
weight between known benefits and risks of all of these techniques for total knee
arthroplasty. RECENT FINDINGS: Femoral nerve blocks are the gold standard for
total knee arthroplasty. The standard use of additional sciatic nerve blocks
remains controversial. Lumbar epidurals possess an unfavourable risk/benefit
ratio because of increased rate of epidural hematoma in orthopaedic patients and
should be reserved for lower limb amputation; peripheral regional techniques
provide comparable pain control, greater satisfaction and less risk than epidural
analgesia. Although motor weakness might be greater with femoral nerve blocks
compared with no regional analgesia, new data point towards a similar risk of
falls after total knee arthroplasty with or without peripheral nerve blocks.
Local infiltration analgesia and adductor canal blockade are promising recent
techniques to gain adequate pain control with a minimum of undesired side
effects. SUMMARY: Femoral nerve blocks are still the gold standard for an
effective analgesia approach in knee arthroplasty and should be supplemented (if
needed) by oral opioids. An additional sciatic nerve blockade is still
controversial and should be an individual decision. Large-scale studies are
needed to reinforce the promising results of newer regional techniques, such as
local infiltration analgesia and adductor canal block.
PMID- 25111603
TI - DNA methylation modifications associated with chronic fatigue syndrome.
AB - Chronic Fatigue Syndrome (CFS), also known as myalgic encephalomyelitis, is a
complex multifactorial disease that is characterized by the persistent presence
of fatigue and other particular symptoms for a minimum of 6 months. Symptoms fail
to dissipate after sufficient rest and have major effects on the daily
functioning of CFS sufferers. CFS is a multi-system disease with a heterogeneous
patient population showing a wide variety of functional disabilities and its
biological basis remains poorly understood. Stable alterations in gene function
in the immune system have been reported in several studies of CFS. Epigenetic
modifications have been implicated in long-term effects on gene function,
however, to our knowledge, genome-wide epigenetic modifications associated with
CFS have not been explored. We examined the DNA methylome in peripheral blood
mononuclear cells isolated from CFS patients and healthy controls using the
Illumina HumanMethylation450 BeadChip array, controlling for invariant probes and
probes overlapping polymorphic sequences. Gene ontology (GO) and network analysis
of differentially methylated genes was performed to determine potential
biological pathways showing changes in DNA methylation in CFS. We found an
increased abundance of differentially methylated genes related to the immune
response, cellular metabolism, and kinase activity. Genes associated with immune
cell regulation, the largest coordinated enrichment of differentially methylated
pathways, showed hypomethylation within promoters and other gene regulatory
elements in CFS. These data are consistent with evidence of multisystem
dysregulation in CFS and implicate the involvement of DNA modifications in CFS
pathology.
PMID- 25111606
TI - Colorectal cancers mimic structural organization of normal colonic crypts.
AB - Colonic crypts are stereotypical structures with distinct stem cell,
proliferating, and differentiating compartments. Colorectal cancers derive from
colonic crypt epithelia but, in contrast, form morphologically disarrayed glands.
In this study, we investigated to which extent colorectal cancers phenocopy
colonic crypt architecture and thus preserve structural organization of the
normal intestinal epithelium. A subset of colon cancers showed crypt-like
compartments with high WNT activity and nuclear beta-Catenin at the leading tumor
edge, adjacent proliferation, and enhanced Cytokeratin 20 expression in most
differentiated tumor epithelia of the tumor center. This architecture strongly
depended on growth conditions, and was fully reproducible in mouse xenografts of
cultured and primary colon cancer cells. Full crypt-like organization was
associated with low tumor grade and was an independent prognostic marker of
better survival in a collection of 221 colorectal cancers. Our findings suggest
that full activation of preserved intestinal morphogenetic programs in colon
cancer requires in vivo growth environments. Furthermore, crypt-like architecture
was linked with less aggressive tumor biology, and may be useful to improve
current colon cancer grading schemes.
PMID- 25111607
TI - Preterm birth related to post-endoscopic retrograde cholangiopancreatography
pancreatitis in pregnancy with newly diagnosed primary sclerosing cholangitis.
PMID- 25111609
TI - Outline-based morphometrics, an overlooked method in arthropod studies?
AB - Modern methods allow a geometric representation of forms, separating size and
shape. In entomology, as well as in many other fields involving arthropod
studies, shape variation has proved useful for species identification and
population characterization. In medical entomology, it has been applied to very
specific questions such as population structure, reinfestation of insecticide
treated areas and cryptic species recognition. For shape comparisons, great
importance is given to the quality of landmarks in terms of comparability. Two
conceptually and statistically separate approaches are: (i) landmark-based
morphometrics, based on the relative position of a few anatomical "true" or
"traditional" landmarks, and (ii) outline-based morphometrics, which captures the
contour of forms through a sequence of close "pseudo-landmarks". Most of the
studies on insects of medical, veterinary or economic importance make use of the
landmark approach. The present survey makes a case for the outline method, here
based on elliptic Fourier analysis. The collection of pseudo-landmarks may
require the manual digitization of many points and, for this reason, might appear
less attractive. It, however, has the ability to compare homologous organs or
structures having no landmarks at all. This strength offers the possibility to
study a wider range of anatomical structures and thus, a larger range of
arthropods. We present a few examples highlighting its interest for separating
close or cryptic species, or characterizing conspecific geographic populations,
in a series of different vector organisms. In this simple application, i.e. the
recognition of close or cryptic forms, the outline approach provided similar
scores as those obtained by the landmark-based approach.
PMID- 25111608
TI - Renal response to L-arginine in diabetic rats. A possible link between nitric
oxide system and aquaporin-2.
AB - The aim of this study was to evaluate whether L-Arginine (L-Arg) supplementation
modifies nitric oxide (NO) system and consequently aquaporin-2 (AQP2) expression
in the renal outer medulla of streptozotocin-diabetic rats at an early time point
after induction of diabetes. Male Wistar rats were divided in four groups:
Control, Diabetic, Diabetic treated with L-Arginine and Control treated with L
Arginine. Nitric oxide synthase (NOS) activity was estimated by [14C] L
citrulline production in homogenates of the renal outer medulla and by NADPH
diaphorase staining in renal outer medullary tubules. Western blot was used to
detect the expression of AQP2 and NOS types I and III; real time PCR was used to
quantify AQP2 mRNA. The expression of both NOS isoforms, NOS I and NOS III, was
decreased in the renal outer medulla of diabetic rats and L-Arg failed to prevent
these decreases. However, L-Arg improved NO production, NADPH-diaphorase activity
in collecting ducts and other tubular structures, and NOS activity in renal
homogenates from diabetic rats. AQP2 protein and mRNA were decreased in the renal
outer medulla of diabetic rats and L-Arg administration prevented these
decreases. These results suggest that the decreased NOS activity in collecting
ducts of the renal outer medulla may cause, at least in part, the decreased
expression of AQP2 in this model of diabetes and constitute additional evidence
supporting a role for NO in contributing to renal water reabsorption through the
modulation of AQP2 expression in this pathological condition. However, we cannot
discard that another pathway different from NOS also exists that links L-Arg to
AQP2 expression.
PMID- 25111610
TI - Dominant modern sublineages and a new modern sublineage of Mycobacterium
tuberculosis Beijing family clinical isolates in Heilongjiang Province, China.
AB - Mycobacterium tuberculosis Beijing family includes a variety of sublineages.
Knowledge of the distribution of a certain sublineage of the Beijing family may
help to understand the mechanisms of its rapid spread and to establish an
association between a certain genotype and the disease outcome. We have
previously found that M. tuberculosis Beijing family clinical isolates represent
approximately 90% of the clinical isolates from Heilongjiang Province, China. To
clarify the distribution of M. tuberculosis Beijing family sublineages in
Heilongjiang Province, China and to investigate the regularity rule for their
evolution, we examined single nucleotide polymorphisms (SNPs) of 250 M.
tuberculosis Beijing family clinical isolates using 10 SNP loci that have been
identified as appropriate for defining Beijing sublineages. After determining the
sequence type (ST) of each isolate, the sublineages of all M. tuberculosis
Beijing family isolates were determined, and phylogenetic analysis was performed.
We found that 9 out of the 10 SNP loci displayed polymorphisms, but locus 1548149
did not. In total, 92.8% of the isolates in Heilongjiang Province are modern
sublineages. ST10 is the most prevalent sublineage (ST10 and ST22 accounted for
63.2% and 23.6% of all the Beijing family isolates, respectively). A new ST,
accounting for 4% of the Beijing family isolates in this area, was found for the
first time. Each new ST isolate showed a unique VNTR pattern, and none were
clustered. The present findings suggest that controlling the spread of these
modern sublineages is important in Heilongjiang Province and in China.
PMID- 25111611
TI - Whole genomic analysis of human G12P[6] and G12P[8] rotavirus strains that have
emerged in Kenya: identification of porcine-like NSP4 genes.
AB - G12 rotaviruses are globally emerging rotavirus strains causing severe childhood
diarrhea. However, the whole genomes of only a few G12 strains have been fully
sequenced and analyzed, of which only one G12P[4] and one G12P[6] are from
Africa. In this study, we sequenced and characterized the complete genomes of
three G12 strains (RVA/Human-tc/KEN/KDH633/2010/G12P[6], RVA/Human
tc/KEN/KDH651/2010/G12P[8], and RVA/Human-tc/KEN/KDH684/2010/G12P[6]) identified
in three stool specimens from children with acute diarrhea in Kenya, Africa. On
whole genomic analysis, all three Kenyan G12 strains were found to have a Wa-like
genetic backbone: G12-P[6]-I1-R1-C1-M1-A1-N1-T1-E1-H1 (strains KDH633 and KDH684)
and G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 (strain KDH651). Phylogenetic analysis
showed that most genes of the three strains examined in this study were
genetically related to globally circulating human G1, G9, and G12 strains. Of
note is that the NSP4 genes of strains KDH633 and KDH684 appeared to be of
porcine origin, suggesting the occurrence of reassortment between human and
porcine strains. Furthermore, strains KDH633 and KDH684 were very closely related
to each other in all the 11 gene segments, indicating derivation of the two
strains from a common origin. On the other hand, strain KDH651 consistently
formed distinct clusters of 10 of the 11 gene segments (VP1-2, VP4, VP6-7, and
NSP1-5), indicating a distinct origin of strain KDH651 from that of strains
KDH633 and KDH684. To our knowledge, this is the first report on whole genome
based characterization of G12 strains that have emerged in Kenya. Our
observations will provide important insights into the evolutionary dynamics of
emerging G12 rotaviruses in Africa.
PMID- 25111613
TI - Spread and predominance in Japan of novel G1P[8] double-reassortant rotavirus
strains possessing a DS-1-like genotype constellation typical of G2P[4] strains.
AB - Rotavirus is a major cause of severe gastroenteritis in children <5 years of age
worldwide, and two, live attenuated rotavirus vaccines are globally available. As
rotavirus vaccines are introduced into national immunization programs, there is
an increasing need to monitor circulating wild-type strains. However, few studies
have systematically examined their full genotype constellation. This study was
therefore undertaken to characterize the whole genotype constellation of
circulating rotavirus strains in three widely-separated locations in Japan during
the 2012 rotavirus season when rotavirus vaccines became available in the country
for the first time. Of 107 rotavirus-positive specimens, 50 (46.7%) strains
collected from all three locations possessed an unusual G1-P[8]-I2-R2-C2-M2-A2-N2
T2-E2-H2 constellation in which a typical G2P[4] strain appeared to have acquired
its two surface protein genes from the most common G1P[8] strain. These G1P[8]
double-reassortant strains were shown to possess the 11 genome segments virtually
indistinguishable from each other in their nucleotide sequences and phylogenetic
lineages except for two strains that underwent further intra-genotype
reassortment. Successful spread to and predominance in broad locations across
Japan of novel rotavirus strains possessing a genotype constellation that was
previously thought not to be preferred suggests unexpected genomic flexibility of
the genotype constellation.
PMID- 25111612
TI - Preponderant clonal evolution of Trypanosoma cruzi I from Argentinean Chaco
revealed by Multilocus Sequence Typing (MLST).
AB - Trypanosoma cruzi has been historically classified as a species with preponderant
clonal evolution (PCE). However, with the advent of highly polymorphic markers
and studies at geographically reduced scales, the PCE in T. cruzi was challenged.
In fact, some studies have suggested that recombination in T. cruzi lineage I
(TcI) is much more frequent than previously believed. Further analyses of TcI
populations from different geographical regions of Latin America are needed to
examine this hypothesis. In the present study, we contribute to this topic by
analyzing the population structure of TcI from a restricted geographical area in
the Chaco region, Argentina. We analyzed TcI isolates from different hosts and
vectors using a Multilocus Sequence Typing (MLST) approach. These isolates were
previously characterized by sequencing the spliced leader intergenic region (SL
IR). Low levels of incongruence and well-supported clusters for MLST dataset were
obtained from the analyses. Moreover, high linkage disequilibrium was found and
five repeated and overrepresented genotypes were detected. In addition, a good
correspondence between SL-IR and MLST was observed which is expected under PCE.
However, recombination is not ruled out because five out of 28 pairs of loci were
incompatible with strict clonality and one possible genetic exchange event was
detected. Overall, our results represent evidence of PCE in TcI from the study
area. Finally, considering our findings we discuss the scenario for the genetic
structure of TcI.
PMID- 25111614
TI - Time and temperature effects on the digestive ripening of gold nanoparticles: is
there a crossover from digestive ripening to Ostwald ripening?
AB - The effects of time and temperature on the gold nanoparticle sizes obtained by
digestive ripening have been investigated. In digestive ripening, a polydisperse
colloid, upon refluxing with a surface-active ligand in a solvent, gets converted
to a nearly monodisperse one. In this study, a polydisperse gold nanoparticle
system was heated in 4-tert-butyltoluene with hexadecanethiol at different
temperatures, viz., 60, 90, 120, 150, and 180 degrees C for different time
periods, and the trends in particle size variations were recorded. At lower
temperatures such as 60 and 90 degrees C, after the initial narrowing of the
size distribution, the particle sizes remain constant even though the refluxing
step is continued for 24 h, substantiating the prevalence of the digestive
ripening process. However, at elevated temperatures (120, 150, and 180 degrees
C) particle sizes grow continuously, indicating a deviation from the digestive
ripening behavior to an Ostwald ripening-type phenomenon.
PMID- 25111615
TI - The effect of surgical margins on outcomes for low grade MPNSTs and atypical
neurofibroma.
AB - BACKGROUND AND OBJECTIVES: While convention defines atypical neurofibroma as
benign and low-grade malignant peripheral nerve sheath tumors (MPNSTs) as
malignant, sparse outcomes data exist for these tumors. This study reviews
clinical outcomes of surgically resected low-grade MPNST and atypical
neurofibroma, focusing on the effect of surgical margins on outcome. METHODS:
This study is a retrospective review of 23 patients who underwent surgical
resection of a low-grade MPNST or atypical neurofibroma. Treatment
characteristics of adjuvant therapy and surgical margin were noted. Endpoints of
local recurrence, presence of metastatic disease, disease-specific survival, and
overall survival were reviewed. RESULTS: Eighteen of 23 patients (78%) had
microscopically positive margins on the resection. Disease-specific survival was
100% for both atypical neurofibroma patients and those with low-grade MPNST,
regardless of surgical margin. Local recurrence in terms of recurrence of
measureable disease occurred in 2/12 (16.7%) of LGMPNST patients and 1/11 (9.1%)
of atypical NF patients, all of whom had microscopically positive surgical
margins. CONCLUSIONS: In a study dedicated exclusively to "intermediate" nerve
sheath tumors, no patients developed metastatic disease nor died of disease
despite a high rate of microscopically positive surgical margins (78%). While
positive margins did lead to increased rates of local recurrence, these data
suggest that surgeons potentially can temper their zeal for negative surgical
margins in the setting of low-grade MPNST and atypical neurofibroma, as surgical
morbidity may be more important than a presumed survival benefit of wide
resection.
PMID- 25111616
TI - SERPINB3/B4 contributes to early inflammation and barrier dysfunction in an
experimental murine model of atopic dermatitis.
AB - Serine proteases are critical for epidermal barrier homeostasis, and their
aberrant expression and/or activity is associated with chronic skin diseases.
Elevated levels of the serine protease inhibitors SERPINB3 and SERPINB4 are seen
in patients with atopic dermatitis and psoriasis. However, their mechanistic role
in the skin is unknown. To evaluate the contribution of Serpinb3a (mouse homolog
of SERPINB3 and SERPINB4) in atopic dermatitis, we examined the effect of topical
Aspergillus fumigatus extract exposure in wild-type and Serpinb3a-null mice on
transepidermal water loss (TEWL), sensitization, and inflammation. Allergen
exposure induced Serpinb3a expression in the skin, along with increased TEWL,
epidermal thickness, and skin inflammation, all of which were attenuated in the
absence of Serpinb3a. Attenuated TEWL correlated with decreased expression of the
pro-inflammatory marker S100A8. Silencing of SERPINB3/B4 in human keratinocytes
decreased S100A8 expression, supporting a role for SERPINB3/B4 in the initiation
of the acute inflammatory response. RNA-seq analysis following allergen exposure
identified a network of pro-inflammatory genes induced in wild-type mice that was
absent in Serpinb3a-null mice. In conclusion, Serpinb3a deficiency attenuates
barrier dysfunction and the early inflammatory response following cutaneous
allergen exposure, supporting a role for Serpinb3a (mice) and SERPINB3/B4
(humans) early in atopic dermatitis.
PMID- 25111618
TI - Long-term IFN-gamma and IL-2 response for detection of latent tuberculosis
infection in healthcare workers with discordant immunologic results.
AB - Discordant results between the interferon-gamma release assays (IGRAs) and
tuberculin skin test (TST) are common in latent tuberculosis infection (LTBI). We
evaluated whether the measurement of IFN-gamma and interleukin (IL)-2T-cell
responses, after prolonged Mycobacterium tuberculosis-specific antigen
stimulation, can be used as adjunctive biomarker for LTBI detection in subjects
with discordant results between TST and QuantiFERON-Gold In-Tube (QFT). 196
healthcare workers were screened for LTBI and in 90 of those participants, the
QFT was repeated after 18 h, and IFN-gamma/IL-2 immune response was measured
after 72 h long-term stimulation. Of the 196 patients, 34 had positive, 155
negative, and 7 indeterminate QFT results. Discordant TST+/QFT- results were
found in 29 (14.7%) patients, of whom 6 (20.6%) were Bacillus Calmette-Guerin
(BCG) vaccinated. None of 23 non-BCG vaccinated subjects showed a specific IFN
gamma immune response after 18 h nor 72 h of incubation, whereas 3/23 (13.04%)
discordant subjects produced a specific long-term IL-2 response, which might
reflect a LTBI status. In LTBI group (TST+/QFT+) both cytokine levels were
increased after long-term in comparison to short-term stimulation. No significant
long-term IFN-gamma/IL-2 secretion was detected in control group (TST-/QFT-).
Taken together, our data showed that the 87% of discordant patients who did not
respond to the long-term assay, as controls subjects, were judged LTBI negative.
The use of classic QFT and long-term IL-2 response may have a potential role to
clarify the LTBI status in individuals in whom the diagnosis of LTBI is uncertain
due to the discordance of the available diagnostic tests, such as TST and IGRA.
PMID- 25111617
TI - Comparison of molecular signatures from multiple skin diseases identifies
mechanisms of immunopathogenesis.
AB - The ability to obtain gene expression profiles from human disease specimens
provides an opportunity to identify relevant gene pathways, but is limited by the
absence of data sets spanning a broad range of conditions. Here, we analyzed
publicly available microarray data from 16 diverse skin conditions in order to
gain insight into disease pathogenesis. Unsupervised hierarchical clustering
separated samples by disease as well as common cellular and molecular pathways.
Disease-specific signatures were leveraged to build a multi-disease classifier,
which predicted the diagnosis of publicly and prospectively collected expression
profiles with 93% accuracy. In one sample, the molecular classifier differed from
the initial clinical diagnosis and correctly predicted the eventual diagnosis as
the clinical presentation evolved. Finally, integration of IFN-regulated gene
programs with the skin database revealed a significant inverse correlation
between IFN-beta and IFN-gamma programs across all conditions. Our study provides
an integrative approach to the study of gene signatures from multiple skin
conditions, elucidating mechanisms of disease pathogenesis. In addition, these
studies provide a framework for developing tools for personalized medicine toward
the precise prediction, prevention, and treatment of disease on an individual
level.
PMID- 25111619
TI - Pattern of Uveitis in a Referral Ophthalmology Center in the Central District of
Thailand.
AB - PURPOSE: To report the pattern of uveitis in a major ophthalmology center in the
central district of Thailand. METHODS: A retrospective study was performed in
uveitis cases visiting the Department of Ophthalmology at Rajavithi Hospital,
Thailand, from January 2007 to October 2012. RESULTS: Four hundred and forty-six
patients (mean age 42 years, female 53.8%) were included in the study. Uveitis
was unilateral in 51.1% of cases. Anterior uveitis was the most common (44.8%)
case, closely followed by panuveitis (40%), posterior uveitis (14.3%), and
intermediate uveitis (0.9%). Specific diagnosis was established in 51.6% of
patients. The three most common specific diagnoses were Vogt-Koyanagi-Harada
(VKH) disease (22.4%), followed by Behcet disease (6.7%) and herpetic anterior
uveitis (5.8%). CONCLUSIONS: The most common type of noninfectious uveitis group
was VKH, while herpetic anterior uveitis was the most common type of infectious
uveitis in the central district of Thailand.
PMID- 25111620
TI - Local protonation control using plasmonic activation.
AB - Localized protonation of 4-mercaptopyridine (4-MPY), activated by light in the
presence of silver nanoparticles is monitored under ambient conditions using
surface-enhanced Raman scattering (SERS) and tip-enhanced Raman scattering
(TERS). The reaction can be controlled by the excitation wavelength and the
atmospheric conditions, thus, providing a tool for site-specific control of
protonation.
PMID- 25111621
TI - Two pediatric liver transplantation guidelines issued by the American Association
for the Study of Liver Diseases: A simple survey of their characteristics.
PMID- 25111622
TI - Troponin T immunosensor based on liquid crystal and silsesquioxane-supported gold
nanoparticles.
AB - A nanostructured immunosensor based on the liquid crystal (E)-1-decyl-4-[(4
decyloxyphenyl)diazenyl]pyridinium bromide (Br-Py) and gold nanoparticles
supported by the water-soluble hybrid material 3-n-propyl-4-picolinium
silsesquioxane chloride (AuNP-Si4Pic(+)Cl(-)) was built for the detection of
troponin T (cTnT), a cardiac marker for acute myocardial infarction (AMI). The
functionalized nanostructured surface was used to bind anti-cTnT monoclonal
antibodies through electrostatic interaction. The immunosensor (ab-cTnT/AuNP
Si4Pic(+)Cl(-)/Br-Py/GCE) surface was characterized by microscopy techniques. The
electrochemical behavior of the immunosensor was studied by cyclic voltammetry
and electrochemical impedance spectroscopy. A calibration curve was obtained by
square-wave voltammetry. The immnunosensor provided a limit of detection of 0.076
ng mL(-1) and a linear range between 0.1 and 0.9 ng mL(-1) (appropriate for AMI
diagnosis).
PMID- 25111623
TI - The reliability of routine clinical post-processing software in assessing
potential diffusion-weighted MRI "biomarkers" in brain metastases, common
mistake.
PMID- 25111624
TI - MR spectroscopy in the diagnosis of bacterial etiology in brain abscesses.
PMID- 25111626
TI - Response to "The reliability of routine clinical post-processing software in
assessing potential diffusion weighted MRI biomarkers in brain metastases: common
mistake".
PMID- 25111625
TI - MR T(1)rho quantification of cartilage focal lesions in acutely injured knees:
correlation with arthroscopic evaluation.
AB - OBJECTIVE: Quantitative T1rho MRI has been suggested as a promising tool to
detect changes in cartilage composition that are characteristic of cartilage
damage and degeneration. The objective of this study was to evaluate the
capability of MR T1rho to detect cartilage lesions as evaluated by arthroscopy in
acutely ACL-injured knees and to compare with the Whole-Organ Magnetic Resonance
Imaging Score (WORMS) using clinical standard MRI. METHOD: Ten healthy controls
(mean age 35) with no ACL injury or history of osteoarthritis (OA) and 10
patients with acute ACL injuries (mean age 39) were scanned at 3 Tesla (3T). ACL
patients underwent ACL reconstruction, where focal lesions were graded according
to an Outerbridge grading system during arthroscopic evaluation. Normalized MR
T1rho values (T1rho z-scores normalized to control values in matched regions) in
full thickness, and superficial and deep layers of cartilage were compared
between defined sub-compartments with and without focal lesions. Intraclass (ICC)
correlation and the root mean square coefficient of variation (RMS-CV) were
performed to evaluate the inter-observer reproducibility of T1rho quantification.
Sub-compartments of cartilage were also evaluated using WORMS scoring and
compared to their Outerbridge score respectively. RESULTS: The inter-observer ICC
and the RMS-CV of the sub-compartment T1rho quantification were 0.961 and 3.9%,
respectively. The average T1rho z-scores were significantly increased in sub
compartments with focal lesions compared to those without focal lesions and to
the control cohort (p<0.05). CONCLUSION: Our results indicate that T1rho provided
a better diagnostic capability than clinical standard MRI grading in detecting
focal cartilage abnormalities after acute injuries. Quantitative MRI may have
great potential in detecting cartilage abnormalities and degeneration non
invasively, which are occult with standard morphological MRI.
PMID- 25111627
TI - Serine versus threonine glycosylation with alpha-O-GalNAc: unexpected selectivity
in their molecular recognition with lectins.
AB - The molecular recognition of several glycopeptides bearing Tn antigen (alpha-O
GalNAc-Ser or alpha-O-GalNAc-Thr) in their structure by three lectins with
affinity for this determinant has been analysed. The work yields remarkable
results in terms of epitope recognition, showing that the underlying amino acid
of Tn (serine or threonine) plays a key role in the molecular recognition. In
fact, while Soybean agglutinin and Vicia villosa agglutinin lectins prefer Tn
threonine, Helix pomatia agglutinin shows a higher affinity for the glycopeptides
carrying Tn-serine. The different conformational behaviour of the two Tn
biological entities, the residues of the studied glycopeptides in the close
proximity to the Tn antigen and the topology of the binding site of the lectins
are at the origin of these differences.
PMID- 25111628
TI - Pigeon (Columba livia) and rat (Rattus norvegicus) performance in the midsession
reversal procedure depends upon cue dimensionality.
AB - Pigeons (Columba livia) produce many anticipatory and perseverative errors on
discrimination tasks with a reversal of reward contingencies partway through the
session. Prior comparative research has suggested that rats (Rattus norvegicus)
do not show the same number of errors and produce results that more closely
resemble those of humans. We examined pigeons' performance on a visual-spatial
discrimination with the reversal point randomized within the session and found
that they showed remarkably few errors. When these subjects were split into
groups with the contingencies for reward unconfounded, the birds in the spatial
contingency group maintained their performance, and those in the visual
contingency group made many more anticipatory and perseverative errors. We also
examined the performance of naive pigeons on a spatial midsession reversal task
and found a pattern of results similar to those shown by pigeons that had
previously been trained on a visual-spatial reversal procedure. Finally, we
studied rats on a T-maze using a spatial-discrimination midsession reversal task
and found that the rats showed a large number of anticipatory and perseverative
errors. Near-perfect performance on the midsession reversal task appears to be
subject to the ability of the animal to orient spatially during the intertrial
interval, rather than being due to broad species differences.
PMID- 25111629
TI - Personality structure in the domestic cat (Felis silvestris catus), Scottish
wildcat (Felis silvestris grampia), clouded leopard (Neofelis nebulosa), snow
leopard (Panthera uncia), and African lion (Panthera leo): a comparative study.
AB - Although the study of nonhuman personality has increased in the last decade,
there are still few studies on felid species, and the majority focus on domestic
cats. We assessed the structure of personality and its reliability in five felids
domestic cats, clouded leopards, snow leopards, African lions, and previous data
on Scottish wildcats-and compared the results. In addition to the benefits of
understanding more about this taxon, comparative studies of personality structure
have the potential to provide information on evolutionary relationships among
closely related species. Each of the species studied was found to have three
factors of personality. Scottish wildcats' factors were labeled Dominance,
Agreeableness, and Self Control; domestic cats' factors were Dominance,
Impulsiveness, and Neuroticism; clouded leopards' factors were
Dominance/Impulsiveness, Agreeableness/Openness, and Neuroticism; snow leopards'
factors were Dominance, Impulsiveness/Openness, and Neuroticism; and African
lions' factors were Dominance, Impulsiveness, and Neuroticism. The Neuroticism
and Impulsiveness factors were similar, as were two of the Dominance factors. A
taxon-level personality structure also showed three similar factors. Age and sex
effects are also discussed.
PMID- 25111630
TI - Shape from shading in starlings (Sturnus vulgaris).
AB - Birds behave as if they quickly and accurately perceive an object-filled visual
world. Beyond the extensive research with pigeons, however, there is a large and
important gap in our knowledge about the mechanisms of object perception and
recognition in other avian visual systems. The pattern of shading reflected from
the surfaces of objects is one important optical feature that provides
fundamental information about shape. To better understand how surface and object
shading is processed by a passerine species, 5 starlings were tested with
differentially illuminated convex and concave curved surfaces in 3 experiments
using a simultaneous visual discrimination procedure. Starlings rapidly learned
this shape-from-shading discrimination independent of varied lighting direction,
surface color, and camera perspective. Variations in the pattern of lighting
through experimental manipulations of camera perspective, surface height,
contrast, material specularity, and surface shape were consistent with the
hypothesis that the starlings perceived these illuminated surfaces as having 3
dimensional shape, similar to results previously collected with pigeons. These
similarities across different orders of birds indicate that the relative shading
of objects in a visual scene is a highly salient feature for shape processing in
birds and is likely a highly conserved visual process that is widely distributed
within this class of animal.
PMID- 25111631
TI - Interspecific communication from people to horses (Equus ferus caballus) is
influenced by different horsemanship training styles.
AB - The ability of many domesticated animals to follow human pointing gestures to
locate hidden food has led to scientific debate on the relative importance of
domestication and individual experience on the origins and development of this
capacity. To further explore this question, we examined the influence of
different prior training histories/methods on the ability of horses (Equus ferus
caballus) to follow a momentary distal point. Ten horses previously trained using
one of two methods (ParelliTM natural horsemanship or traditional horse training)
were tested using a standard object choice task. The results show that neither
group of horses was initially able to follow the momentary distal point. However,
after more experience with the point, horses previously trained using the Parelli
natural horsemanship method learned to follow momentary distal points
significantly faster than those previously trained with traditional methods. The
poor initial performance of horses on distal pointing tasks, coupled with the
finding that prior training history and experimental experience can lead to
success on this task, fails to support the predictions of the domestication
hypothesis and instead lends support to the two-stage hypothesis.
PMID- 25111633
TI - Right anterior thoracotomy aortic valve replacement is associated with less cost
than sternotomy-based approaches: a multi-institution analysis of 'real world'
data.
AB - BACKGROUND: Large institutional analyses demonstrating outcomes of right anterior
mini-thoracotomy (RAT) for isolated aortic valve replacement (isoAVR) do not
exist. In this study, a group of cardiac surgeons who routinely perform minimally
invasive isoAVR analyzed a cross-section of US hospital records in order to
analyze outcomes of RAT as compared to sternotomy. METHODS: The Premier database
was queried from 2007-2011 for clinical and cost data for patients undergoing
isoAVR. This de-identified database contains billing, hospital cost, and coding
data from >600 US facilities with information from >25 million inpatient
discharges. Expert rules were developed to identify patients with RAT and those
with any sternal incision (aStern). Propensity matching created groups adjusted
for patient differences. The impact of surgical approach on outcomes and costs
was modeled using regression analysis and, where indicated, adjusting for
hospital size and geographical differences. RESULTS: AVR was performed in 27,051
patients. Analysis identified isoAVR by RAT (n = 1572) and by aStern (n = 3962).
Propensity matching created two groups of 921 patients. RAT was more likely
performed in southern hospitals (63% vs 36%; p < 0.01), teaching hospitals (66%
vs 58%; p < 0.01) and larger hospitals (47% vs 30%; p < 0.01). There was
significantly less blood product cost associated with RAT ($1381 vs $1912; p <
0.001). After adjusting for hospital differences, RAT was associated with lower
cost than aStern ($38,769 vs $42,656; p < 0.01). CONCLUSIONS: Outcomes analyses
can be performed from hospital administrative collective databases. This real
world analysis demonstrates comparable outcomes and less cost and ICU time with
RAT for AVR.
PMID- 25111634
TI - Costs and utilization of hemophilia A and B patients with and without inhibitors.
AB - OBJECTIVE: To evaluate the health system costs among patients with hemophilia A
and B with and without inhibitors over 5 years. METHODS: This was a
retrospective, observational study utilizing medical and pharmacy electronic
medical records and administrative encounters/claims data tracking US patients
between 2006-2011. Patients with diagnosis codes for hemophilia A and B were
identified. Patients with inhibitors were characterized by utilization of
bypassing agents activated prothrombin complex concentrate or factor VIIa on two
or more distinct dates. Severity was classified as mild, moderate, or severe
based on laboratory tests of clotting factor. RESULTS: There were 160 hemophilia
A patients and 54 hemophilia B patients identified. From this group, seven were
designated as patients with inhibitors (five with hemophilia A and two with
hemophilia B). Hemophilia A patients without inhibitors reported 65 (41.9%) as
being severe, 19 (12.3%) as moderate, and 71 (45.8%) as mild. Hemophilia B
patients without inhibitors reported nine (17.3%) had severe, 13 (25.0%) had
moderate, and 30 (57.7%) had mild hemophilia. All patients with inhibitors had
been hospitalized in the previous 5 years compared to 64 (41.3%) with hemophilia
A without inhibitors and 22 (42.3%) with hemophilia B without inhibitors. The
median aggregate cost per year (including factor and health resource use) was
$325,780 for patients with inhibitors compared to $98,334 for hemophilia A
patients without inhibitors and $23,265 for hemophilia B patients without
inhibitors. CONCLUSIONS: The results suggest that, while the frequency of
inhibitors within the hemophilia cohort was low, there was a higher frequency of
hospitalizations, and the associated median aggregate costs per year were 3-fold
higher than those patients without inhibitors. In contrast, hemophilia B patients
experience less severe disease and account for lower aggregate yearly costs
compared to either patients with hemophilia A or patients with inhibitors.
PMID- 25111632
TI - Chemical interrogation of the malaria kinome.
AB - Malaria, an infectious disease caused by eukaryotic parasites of the genus
Plasmodium, afflicts hundreds of millions of people every year. Both the parasite
and its host utilize protein kinases to regulate essential cellular processes.
Bioinformatic analyses of parasite genomes predict at least 65 protein kinases,
but their biological functions and therapeutic potential are largely unknown. We
profiled 1358 small-molecule kinase inhibitors to evaluate the role of both the
human and the malaria kinomes in Plasmodium infection of liver cells, the
parasites' obligatory but transient developmental stage that precedes the
symptomatic blood stage. The screen identified several small molecules that
inhibit parasite load in liver cells, some with nanomolar efficacy, and each
compound was subsequently assessed for activity against blood-stage malaria. Most
of the screening hits inhibited both liver- and blood-stage malaria parasites,
which have dissimilar gene expression profiles and infect different host cells.
Evaluation of existing kinase activity profiling data for the library members
suggests that several kinases are essential to malaria parasites, including
cyclin-dependent kinases (CDKs), glycogen synthase kinases, and phosphoinositide
3-kinases. CDK inhibitors were found to bind to Plasmodium protein kinase 5, but
it is likely that these compounds target multiple parasite kinases. The dual
stage inhibition of the identified kinase inhibitors makes them useful chemical
probes and promising starting points for antimalarial development.
PMID- 25111635
TI - The characteristics of n- and p-type dopants in SnS2 monolayer nanosheets.
AB - Based on density functional theory, the characteristics of n- and p-type
impurities are investigated firstly by means of group V and VII atoms
substituting sulfur atoms in the SnS2 monolayer nanosheets. Numerical results
show that the formation energy and transition levels depend highly on the atomic
size and electronegativity of the impurity atom. The formation energies increase
with the increasing impurity atom size for each considered doping case. For group
V atom-doped SnS2 monolayer nanosheet systems, the calculations of the transition
level indicate that N, P or As doping is not effective for p-type conductivity.
However, for group VII atom doping cases, F, Cl, Br and I impurities can offer
effective n-type carriers in the SnS2 monolayer nanosheets.
PMID- 25111638
TI - The first case of a patient with de novo partial distal 16q tetrasomy and a
data's review.
AB - We report on a patient with severe psychomotor disability, numerous dysmorphic
features, and congenital malformations resulting from a complex genomic
rearrangement on 16q24.1-q24.3 involving a de novo duplication-triplication
pattern. To the best of our knowledge, this is the first reported patient
presenting with this aberration within the distal chromosome 16q. We suggest that
the clinical phenotype of our patient results from over-dosage of genes mapped to
the region with duplication/triplication (five genes: FOXF1, FOXC2, ANKRD11, SPG7
and FANCA seem to play a peculiar role). Detailed molecular characterization and
documentation of the complex genomic rearrangement observed in the proband and of
the clinical presentation are important for accurate genotype-phenotype
correlations in genetic counseling. Delineation of the gene map for the terminal
region of chromosome 16q will provide insight into this chromosome 16q24.1-q24.3
contiguous gene duplication-triplication syndrome.
PMID- 25111636
TI - Nanostructure embedded microchips for detection, isolation, and characterization
of circulating tumor cells.
AB - Circulating tumor cells (CTCs) are cancer cells that break away from either a
primary tumor or a metastatic site and circulate in the peripheral blood as the
cellular origin of metastasis. With their role as a "tumor liquid biopsy", CTCs
provide convenient access to all disease sites, including that of the primary
tumor and the site of fatal metastases. It is conceivable that detecting and
analyzing CTCs will provide insightful information in assessing the disease
status without the flaws and limitations encountered in performing conventional
tumor biopsies. However, identifying CTCs in patient blood samples is technically
challenging due to the extremely low abundance of CTCs among a large number of
hematologic cells. To address this unmet need, there have been significant
research endeavors, especially in the fields of chemistry, materials science, and
bioengineering, devoted to developing CTC detection, isolation, and
characterization technologies. Inspired by the nanoscale interactions observed in
the tissue microenvironment, our research team at UCLA pioneered a unique concept
of "NanoVelcro" cell-affinity substrates, in which CTC capture agent-coated
nanostructured substrates were utilized to immobilize CTCs with high efficiency.
The working mechanism of NanoVelcro cell-affinity substrates mimics that of
Velcro: when the two fabric strips of a Velcro fastener are pressed together,
tangling between the hairy surfaces on two strips leads to strong binding.
Through continuous evolution, three generations (gens) of NanoVelcro CTC chips
have been established to achieve different clinical utilities. The first-gen
NanoVelcro chip, composed of a silicon nanowire substrate (SiNS) and an overlaid
microfluidic chaotic mixer, was created for CTC enumeration. Side-by-side
analytical validation studies using clinical blood samples suggested that the
sensitivity of first-gen NanoVelcro chip outperforms that of FDA-approved
CellSearch. In conjunction with the use of the laser microdissection (LMD)
technique, second-gen NanoVelcro chips (i.e., NanoVelcro-LMD), based on polymer
nanosubstrates, were developed for single-CTC isolation. The individually
isolated CTCs can be subjected to single-CTC genotyping (e.g., Sanger sequencing
and next-generation sequencing, NGS) to verify the CTC's role as tumor liquid
biopsy. Created by grafting of thermoresponsive polymer brushes onto SiNS, third
gen NanoVelcro chips (i.e., Thermoresponsive NanoVelcro) have demonstrated the
capture and release of CTCs at 37 and 4 degrees C, respectively. The temperature
dependent conformational changes of polymer brushes can effectively alter the
accessibility of the capture agent on SiNS, allowing for rapid CTC purification
with desired viability and molecular integrity. This Account summarizes the
continuous evolution of NanoVelcro CTC assays from the emergence of the original
idea all the way to their applications in cancer research. We envision that
NanoVelcro CTC assays will lead the way for powerful and cost-efficient
diagnostic platforms for researchers to better understand underlying disease
mechanisms and for physicians to monitor real-time disease progression.
PMID- 25111639
TI - Influence on quality of life from an early cinacalcet prescription for secondary
hyperparathyroidism in dialysis.
AB - OBJECTIVE: The goal of this study is to compare patient-reported quality of life
(PRQOL) evolution between two groups of end-stage renal disease patients with
secondary hyperparathyroidism (SHPT). The first with a cinacalcet prescription
within 3 months after a diagnosis of SHPT (early group) and a second group of
patients with a later or no cinacalcet prescription (nonearly group). PATIENTS
AND METHODS: From 2009 to 2012, we conducted a multicenter pharmaco-epidemiologic
study in Lorraine region (France) including all consecutive patients on
maintenance dialysis for at least 3 months with a diagnosis of SHPT (PTH > 500
pg/ml or first cinacalcet prescription). PRQOL was estimated using the Kidney
Disease Quality Of Life-Short Form questionnaire, at baseline and at 6 and 12
months follow-up. Change in PRQOL was compared between the groups and adjusted
with a propensity score. RESULTS: We included 124 patients: 44 in the early group
and 80 in the nonearly group. The mental component summary score was lower in the
early group, at baseline (43.6 +/- 6.6 vs 46.6 +/- 7.6; p = 0.030), and at the
follow-up assessment (42.6 +/- 6.9 vs 45.7 +/- 7.9; p = 0.033). We found no
difference between the groups in change in PRQOL, for all dimensions, even after
adjustment with the propensity score. Mean serum alkaline phosphatase levels were
normal in both groups at baseline (80.9 +/- 32.5 vs 95.1 +/- 39.6; p = 0.41).
CONCLUSION: Cinacalcet prescription immediately following diagnosis of SHPT does
not seem to be associated with better PRQOL evolution at 1 year. Mean serum
alkaline phosphatase levels suggest that physicians should consider waiting for
another PTH assay result before starting cinacalcet in case of a PTH rise.
PMID- 25111640
TI - Ventilatory strategies in severe acute respiratory failure.
AB - Lung-protective ventilator strategies are considered standard practice in the
care of patients with the acute respiratory distress syndrome (ARDS). To minimize
ventilator-induced lung injury, attention is directed at avoidance of alveolar
overdistention and cyclical opening and closing. The lowest possible plateau
pressure and tidal volume (V(T)) should be selected. A reasonable target V(T) in
all mechanically ventilated patients is 6 mL/kg. A topic of much controversy is
the optimal setting of positive end-expiratory pressure (PEEP). Results of a meta
analysis using individual patient data from three randomized controlled trials
suggest that higher PEEP should be used for moderate and severe ARDS, whereas
lower PEEP may be more appropriate in patients with mild ARDS. PEEP should be set
to maximize alveolar recruitment while avoiding overdistention. Volume and
pressure limitation during mechanical ventilation can be described in terms of
stress and strain. Fraction of inspired oxygen (Fio(2)) and PEEP are typically
titrated to maintain arterial oxygen saturation (Spo(2)) of 88 to 95% (Pao(2) 55
80 mm Hg). There is currently no clear proven benefit for advanced modes.
PMID- 25111641
TI - Ventilatory strategies in obstructive lung disease.
AB - Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow
limitation (EFL) due to progressive airflow obstruction. The various mechanisms
that cause EFL are central to understanding the physiopathology of COPD. At the
end of expiration, dynamic inflation may occur due to incomplete emptying the
lungs. This "extra" volume increases the alveolar pressure at the end of the
expiration, resulting in auto-positive end-expiratory pressure (PEEP) or PEEPi.
Acute exacerbations of COPD may result in increased airway resistance and
inspiratory effort, further leading to dynamic hyperinflation. COPD exacerbations
may be triggered by environmental exposures, infections (viral and bacterial), or
bronchial inflammation, and may result in worsening respiratory failure requiring
mechanical ventilation (MV). Acute exacerbations of COPD need to be distinguished
from other events such as cardiac failure or pulmonary emboli. Strategies to
treat acute respiratory failure (ARF) in COPD patients include noninvasive
ventilation (NIV), pressure support ventilation, and tracheal intubation with MV.
In this review, we discuss invasive and noninvasive techniques to address ARF in
this patient population. When invasive MV is used, settings should be adjusted in
a way that minimizes hyperinflation, while providing reasonable gas exchange,
respiratory muscle rest, and proper patient-ventilator interaction. Further,
weaning from MV may be difficult in these patients, and factors amenable to
pharmacological correction (such as increased bronchial resistance,
tracheobronchial infections, and heart failure) are to be systematically searched
and treated. In selected patients, early use of NIV may hasten the process of
weaning from MV and improve outcomes.
PMID- 25111642
TI - Sedation and analgesia in mechanical ventilation.
AB - Traditionally, critically ill patients undergoing mechanical ventilation (MV)
have received sedation. Over the last decade, randomized controlled trials have
questioned continued use of deep sedation. Evidence shows that a nurse-driven
sedation protocol reduces length of MV compared with standard strategy with
sedation. Furthermore, daily interruption of sedation reduces length of MV,
intensive care unit (ICU), and hospital length of stay (LOS). A larger scale
trial with daily interruption of sedation has confirmed these findings and
furthermore showed a reduction in 1-year mortality with the use of daily
interruption of sedation. Recently, a strategy with no sedation has been
described reporting a reduction in length of MV, ICU, and hospital LOS compared
with a strategy with daily interruption of sedation. Follow-up trials report that
reducing sedation does not seem to increase the risk of psychological morbidity.
Moreover, delirium has gained increased focus in recent years with development of
validated tools to detect both hyperactive and hypoactive forms of delirium.
Using validated tools for detecting delirium is important in monitoring and
detecting acute brain dysfunction in critically ill patients. Evidence from
randomized trials also cites a beneficial effect of early mobilization with
respect to length of MV and delirium.
PMID- 25111643
TI - Ventilator-associated pneumonia.
AB - Ventilator-associated pneumonia (VAP) is an iatrogenic pulmonary infection that
develops in tracheally intubated patients on mechanical ventilation for at least
48 hours. VAP is the nosocomial infection with the greatest impact on patient
outcomes and health care costs. Endogenous colonization by aerobic gram-negative
pathogens, that is, Pseudomonas aeruginosa, and methicillin-resistant
Staphylococcus aureus play a pivotal role in the pathogenesis of VAP. Several
preventive strategies have shown efficacy in decreasing VAP incidence and are
often implemented altogether as a prevention bundle. In patients with clinical
suspicion of VAP, respiratory samples should be promptly collected. The empiric
treatment should be based on the local prevalence of pathogens, duration of
hospital stay, and prior antimicrobial therapy. The antibiotics can be stopped or
adjusted to more narrow-spectrum once cultures and susceptibilities are
available.
PMID- 25111644
TI - Tracheostomy in mechanical ventilation.
AB - Airway access for mechanical ventilation (MV) can be provided either by
orotracheal intubation (OTI) or tracheostomy tube. During episodes of acute
respiratory failure, patients are commonly ventilated through an orotracheal tube
that represents an easy and rapid initial placement of the airway device. OTI
avoids acute surgical complications such as bleeding, nerve and posterior
tracheal wall injury, and late complications such as wound infection and tracheal
lumen stenosis that may emerge due to tracheostomy tube placement. Tracheostomy
is often considered when MV is expected to be applied for prolonged periods or
for the improvement of respiratory status, as this approach provides airway
protection, facilitates access for secretion removal, improves patient comfort,
and promotes progression of care in and outside the intensive care unit (ICU).
The aim of this review is to assess the frequency and performance of different
surgical or percutaneous dilational tracheostomy and timing and safety procedures
associated with the use of fiberoptic bronchoscopy and ultrasounds. Moreover, we
analyzed the performance based on National European surveys to assess the current
tracheostomy practice in ICUs.
PMID- 25111645
TI - Noninvasive ventilation for patients with hypoxemic acute respiratory failure.
AB - Noninvasive ventilation (NIV) has an established efficacy to improve gas exchange
and reduce the work of breathing in patients with hypoxemic acute respiratory
failure. The clinical efficacy in terms of meaningful outcome is less clear and
depends very much on patient selection and assessment of the risks of the
technique. The potential risks include an insufficient reduction of the oxygen
consumption of the respiratory muscles in case of shock, an excessive increase in
tidal volume in case of lung injury, and a risk of delayed or emergent
intubation. With a careful selection of patients and a rapid decision regarding
the need for intubation in case of failure, great benefits can be offered to
patients. Emerging indications include its use in patients with treatment
limitations, in the postoperative period, and in patients with immunosuppression.
This last indication will necessitate reappraisal because the prognosis of the
conditions associated with immunosuppression has improved over the years. In all
cases, there is both a time window and a severity window for NIV to work, after
which delaying endotracheal intubation may worsen outcome. The preventive use of
NIV seems promising in this setting but needs more research. An emerging
interesting new option is the use of high flow humidified oxygen, which seems to
be intermediate between oxygen alone and NIV.
PMID- 25111646
TI - Noninvasive ventilation in acute hypercapnic respiratory failure.
AB - Noninvasive mechanical ventilation (NIV) improves gas exchange and clinical
outcome in various types of acute respiratory failure. Acute exacerbation of
chronic obstructive pulmonary disease is a frequent cause of acute hypercapnic
respiratory failure (AHRF). According to several randomized controlled trials,
the addition of NIV to standard medical therapy reduces mortality, intubation
rate, and hospital length of stay in these patients. Indications for the use of
NIV have expanded over the past decade. In this article, we discuss the clinical
indications and goals of NIV in the management of AHRF.
PMID- 25111647
TI - Noninvasive ventilation in withdrawal from mechanical ventilation.
AB - Patients with chronic airflow obstruction and difficult or prolonged weaning are
at increased risk for prolonged invasive mechanical ventilation (IMV). Several
randomized controlled trials mainly conducted in patients who had pre-existing
lung disease have shown that the use of noninvasive ventilation (NIV) to advance
extubation in patients with difficult and prolonged weaning can result in reduced
periods of endotracheal intubation, complication rates, and improved survival.
Patients in these studies were hemodynamically stable, with a normal level of
consciousness, no fever, and a preserved cough reflex. The use of NIV in the
management of mixed populations with respiratory failure after extubation,
including small proportions of chronic respiratory patients did not show clinical
benefits included. By contrast, NIV immediately after extubation is effective in
avoiding respiratory failure after extubation and improving survival in patients
at risk for this complication, particularly those with chronic respiratory
disorders, cardiac comorbidity, and hypercapnic respiratory failure. Finally,
both continuous positive airway pressure and NIV can improve clinical outcomes in
patients with postoperative acute respiratory failure, particularly abdominal and
thoracic surgery.
PMID- 25111648
TI - Extracorporeal support for severe acute respiratory failure.
AB - Extracorporeal membrane oxygenation (ECMO) and extracorporeal CO(2) removal
(ECCO(2)R) techniques have increasingly been applied in patients with severe
acute lung injury refractory to conventional mechanical ventilatory support. The
objectives of this article are to review current concepts of extracorporeal life
support techniques (ECMO and ECCO(2)R systems) and provide the rationale for
their application in patients with acute respiratory distress syndrome, chronic
obstruction pulmonary disease, and as adjunctive therapy for bridging patients to
lung transplantation.
PMID- 25111649
TI - Late prematurity in twins: a Polish multicenter study.
AB - The study aimed at investigating the impact of late prematurity (LPT) on neonatal
outcome in twins and neonatal morbidity and mortality within LPT with regard to
the completed weeks of gestation. The study was conducted in six tertiary
obstetric departments from different provinces of Poland (Warsaw, Lublin, Poznan,
Wroclaw, Bytom). It included 465 twin deliveries in the above centers in 2012. A
comparative analysis of maternal factors, the course of pregnancy and delivery
and neonatal outcome between LPT (34 + 0-36 + 6 weeks of gestation) and term
groups (completed 37 weeks) was performed. The neonatal outcome included short
term morbidities. The analysis of neonatal complication rates according to
completed gestational weeks was carried out. Out of 465 twin deliveries 213
(44.8%) were LPT and 156 (33.55%) were term. There were no neonatal deaths among
LPT and term twins. One-third of LPT newborns suffered from respiratory disorders
or required antibiotics, 40% had jaundice requiring phototherapy, and 30% were
admitted to NICU. The analysis of neonatal morbidity with regard to each
gestational week at delivery showed that most analyzed complications occurred
less frequently with the advancing gestational age, especially respiratory
disorders and NICU admissions. The only two factors with significant influence on
neonatal morbidity rate were neonatal birth weight (OR = 0.43, 95% CI = 0.2-0.9,
p = .02) and gestational age at delivery (OR = 0.62, 95% CI = 0.5-0.8, p < .01).
LPT have a higher risk of neonatal morbidity than term twins. Gestational age and
neonatal birth weight seem to play a crucial role in neonatal outcome in twins.
PMID- 25111652
TI - Responses of 9 lepidopteran species to Bacillus thuringiensis: How useful is
phylogenetic relatedness for selecting surrogate species for nontarget arthropod
risk assessment?
AB - To evaluate phylogenetic relatedness as a proxy for susceptibility to Bacillus
thuringiensis (Bt) when selecting species to act as surrogates for others in
prerelease testing, we examined the responses of 11 laboratory-reared
lepidopteran colonies, comprising members of 2 families, 5 genera, and 9 species,
to a commercial Bt preparation. Survival, pupal mass, and timing of pupation and
adult emergence of 2 noctuids (Spodoptera litura and Helicoverpa armigera) and 7
tortricids (Cnephasia jactatana, Ctenopseustis obliquana, Ctenopseustis
herana,Planotortrix octo, Planotortrix notophaea,Planotortrix excessana [2
different laboratory colonies], and Epiphyas postvittana [2 colonies]) were
examined after feeding first instar larvae with artificial diet containing 5
MUL/100 mL Dipel ES (Bt subsp. kurstaki). Bt caused significant larval mortality
in all species except S. litura, in which only pupation was delayed compared with
untreated controls. Neither of the noctuid species tested would act as a suitable
surrogate for the other in tests of Bt impacts on survival. With the exception of
the 2 colonies of E. postvittana, which differed from each other not only in
their responses to Bt but also in their development times when not treated with
Bt, species within each tortricid genus had similar responses to Bt and thus
could act as surrogates for each other. Members of different genera within this
family could represent each other only if relatively coarse measurement endpoints
(e.g., toxic or not) were considered adequate for assessing risks to nontarget
species in the field.
PMID- 25111650
TI - Nuclear overhauser enhancement mediated chemical exchange saturation transfer
imaging at 7 Tesla in glioblastoma patients.
AB - BACKGROUND AND PURPOSE: Nuclear Overhauser Enhancement (NOE) mediated chemical
exchange saturation transfer (CEST) is a novel magnetic resonance imaging (MRI)
technique on the basis of saturation transfer between exchanging protons of
tissue proteins and bulk water. The purpose of this study was to evaluate and
compare the information provided by three dimensional NOE mediated CEST at 7
Tesla (7T) and standard MRI in glioblastoma patients. PATIENTS AND METHODS:
Twelve patients with newly diagnosed histologically proven glioblastoma were
enrolled in this prospective ethics committee-approved study. NOE mediated CEST
contrast was acquired with a modified three-dimensional gradient-echo sequence
and asymmetry analysis was conducted at 3.3 ppm (B1 = 0.7 uT) to calculate the
magnetization transfer ratio asymmetry (MTR(asym)). Contrast enhanced T1 (CE-T1)
and T2-weighted images were acquired at 3T and used for data co-registration and
comparison. RESULTS: Mean NOE mediated CEST signal based on MTR(asym) values over
all patients was significantly increased (p<0.001) in CE-T1 tumor (-1.99 +/-
1.22%), tumor necrosis (-1.36 +/- 1.30%) and peritumoral CEST hyperintensities
(PTCH) within T2 edema margins (-3.56 +/- 1.24%) compared to contralateral normal
appearing white matter (-8.38 +/- 1.19%). In CE-T1 tumor (p = 0.015) and tumor
necrosis (p<0.001) mean MTR(asym) values were significantly higher than in PTCH.
Extent of the surrounding tumor hyperintensity was smaller in eight out of 12
patients on CEST than on T2-weighted images, while four displayed at equal size.
In all patients, isolated high intensity regions (0.40 +/- 2.21%) displayed on
CEST within the CE-T1 tumor that were not discernible on CE-T1 or T2-weighted
images. CONCLUSION: NOE mediated CEST Imaging at 7 T provides additional
information on the structure of peritumoral hyperintensities in glioblastoma and
displays isolated high intensity regions within the CE-T1 tumor that cannot be
acquired on CE-T1 or T2-weighted images. Further research is needed to determine
the origin of NOE mediated CEST and possible clinical applications such as
therapy assessment or biopsy planning.
PMID- 25111654
TI - The National ALS Registry: a recruitment tool for research.
AB - INTRODUCTION: Subject recruitment is critical for understanding fatal diseases
like ALS, however linking patients with researchers can be challenging. The U.S.
population-based National ALS Registry allows recruitment of persons with ALS
(PALS) for research opportunities. METHODS: The Registry's Research Notification
Mechanism was used to recruit PALS aged >=21 years; participants completed a Web
based epidemiologic survey. PALS (n = 2,232) were sent an email describing the
study, and 268 surveys were completed. RESULTS: The mean age (+/- SD) of eligible
participants was 57.7 +/- 9.3 years for men and 61.5 +/- 8.9 for women. Most were
men (63%) and Caucasian (92%). Of 256 potentially eligible participants, 37.5% (n
= 96) returned an authorization to disclose protected health information. ALS was
confirmed for 94% (83/88) from physician responses. CONCLUSIONS: This analysis
demonstrates the National ALS Registry's usefulness in recruiting PALS for
research. This recruitment source can potentially foster the discovery of better
treatment options and therapies, and of prevention strategies.
PMID- 25111656
TI - Post-traumatic olfactory loss: psychophysical, electrophysiological and
neuroradiological findings in three single case studies.
AB - BACKGROUND: Traumatic brain injury is one of the main causes of smell disorders.
The degree of olfactory loss may vary and depend on the severity, nature and
location of injury within the olfactory system. The diagnosis of disorders of the
sense of smell is based on medical history and clinical data supported by
psychophysical tests of smell, electrophysiological and neuroimaging measures.
METHODS: This study reports three single clinical cases of post-traumatic anosmia
evaluated by Sniffin' Sticks Test, Olfactory Event-Related Potential and Magnetic
Resonance Imaging examinations. RESULTS: The Olfactory Event-Related Potential
findings confirmed the presence of functional olfactory impairment in all three
post-traumatic patients showing a good correlation with results of the
psychophysical testing. In particular, Sniffin' Sticks Test and OERPs allowed to
demonstrate the functional nature of post-traumatic olfactory loss, while the MRI
identified the location and extent of injury compatible with the olfactory
disorder. CONCLUSIONS: OERPs may have a good clinical application in objective
diagnosis of post-traumatic anosmia, especially when the neuroradiological
examination does not show lesions compatible with olfactory loss.
PMID- 25111655
TI - Somatostatin analogues for receptor targeted photodynamic therapy.
AB - Photodynamic therapy (PDT) is an established treatment modality, used mainly for
anticancer therapy that relies on the interaction of photosensitizer, light and
oxygen. For the treatment of pathologies in certain anatomical sites, improved
targeting of the photosensitizer is necessary to prevent damage to healthy
tissue. We report on a novel dual approach of targeted PDT (vascular and cellular
targeting) utilizing the expression of neuropeptide somatostatin receptor (sst2)
on tumor and neovascular-endothelial cells. We synthesized two conjugates
containing the somatostatin analogue [Tyr3]-octreotate and Chlorin e6 (Ce6): Ce6
K3-[Tyr3]-octreotate (1) and Ce6-[Tyr3]-octreotate-K3-[Tyr3]-octreotate (2).
Investigation of the uptake and photodynamic activity of conjugates in-vitro in
human erythroleukemic K562 cells showed that conjugation of [Tyr3]-octreotate
with Ce6 in conjugate 1 enhances uptake (by a factor 2) in cells over-expressing
sst2 compared to wild-type cells. Co-treatment with excess free Octreotide
abrogated the phototoxicity of conjugate 1 indicative of a specific sst2-mediated
effect. In contrast conjugate 2 showed no receptor-mediated effect due to its
high hydrophobicity. When compared with un-conjugated Ce6, the PDT activity of
conjugate 1 was lower. However, it showed higher photostability which may
compensate for its lower phototoxicity. Intra-vital fluorescence pharmacokinetic
studies of conjugate 1 in rat skin-fold observation chambers transplanted with
sst2+ AR42J acinar pancreas tumors showed significantly different uptake profiles
compared to free Ce6. Co-treatment with free Octreotide significantly reduced
conjugate uptake in tumor tissue (by a factor 4) as well as in the chamber neo
vasculature. These results show that conjugate 1 might have potential as an in
vivo sst2 targeting photosensitizer conjugate.
PMID- 25111657
TI - Definition and applications of a versatile chemical pollution footprint
methodology.
AB - Because of the great variety in behavior and modes of action of chemicals, impact
assessment of multiple substances is complex, as is the communication of its
results. Given calls for cumulative impact assessments, we developed a
methodology that is aimed at expressing the expected cumulative impacts of
mixtures of chemicals on aquatic ecosystems for a region and subsequently allows
to present these results as a chemical pollution footprint, in short: a chemical
footprint. Setting and using a boundary for chemical pollution is part of the
methodology. Two case studies were executed to test and illustrate the
methodology. The first case illustrates that the production and use of organic
substances in Europe, judged with the European water volume, stays within the
currently set policy boundaries for chemical pollution. The second case shows
that the use of pesticides in Northwestern Europe, judged with the regional water
volume, has exceeded the set boundaries, while showing a declining trend over
time. The impact of mixtures of substances in the environment could be expressed
as a chemical footprint, and the relative contribution of substances to that
footprint could be evaluated. These features are a novel type of information to
support risk management, by helping prioritization of management among chemicals
and environmental compartments.
PMID- 25111658
TI - Baseline adherence to the Mediterranean diet and major cardiovascular events:
Prevencion con Dieta Mediterranea trial.
PMID- 25111659
TI - Subgroups of familial and aggressive prostate cancer with considerable
frequencies of BRCA2 mutations.
AB - BACKGROUND: One of the known risk factors for prostate cancer (PrCa) is germline
mutations in the BRCA2 gene. Previous searches for clinical characteristics which
could identify a subgroup of patients enriched for mutation carriers revealed
early onset and aggressive PrCa as useful parameters, but they are rather
unspecific. METHODS: Identification of BRCA2 mutation carriers by sequencing all
exons of BRCA2 in a German cohort of 382 familial PrCa cases and of 92 sporadic
PrCa cases with early onset (<=60 years). To define a subgroup of PrCa patients
enriched for BRCA2 mutation carriers, we used clinical parameters including a
detailed family history (FH) for PrCa and breast cancer. RESULTS: Five BRCA2
mutations and ten variants of unknown significance (VUS) were identified. While
the VUS were evenly distributed among the groups, mutation carriers were lacking
from the sporadic cases and over represented among familial cases with aggressive
disease. High prostate specific antigen (PSA) at diagnosis (>20 ng/ml) was the
only criterion with significant enrichment of mutation carriers (6.4%, P =
0.0005). In men with aggressive disease, death from PrCa (6.3% including FH of
lethal PrCa; P = 0.05) and FH of both prostate and breast cancer (4.8%; P = 0.3)
increased the frequency of mutation carriers. Larger studies and/or meta-analyses
are needed to validate these parameters. CONCLUSIONS: We have identified three
potentially useful criteria, high PSA, death from PrCa (patient or FH), and
aggressive PrCa in combination with FH of breast and prostate cancer. If
confirmed, they may become useful for the decision which patients may benefit
from BRCA2 testing.
PMID- 25111660
TI - The berry constituents quercetin, kaempferol, and pterostilbene synergistically
attenuate reactive oxygen species: involvement of the Nrf2-ARE signaling pathway.
AB - Quercetin, kaempferol, and pterostilbene are abundant in berries. The anti
oxidative properties of these constituents may contribute to cancer
chemoprevention. However, their precise mechanisms of action and their
combinatorial effects are not completely understood. Nuclear factor (erythroid
derived 2)-like 2 (Nrf2) regulates anti-oxidative stress enzymes and Phase II
drug metabolizing/detoxifying enzymes by binding to antioxidant response element
(ARE). This study aimed to investigate the anti-oxidative stress activities of
quercetin, kaempferol, and pterostilbene individually and in combination, as well
as the involvement of the Nrf2-ARE signaling pathway. Quercetin, kaempferol, and
pterostilbene all exhibited strong free-radical scavenging activity in the DPPH
assay. The MTS assay revealed that low concentration combinations we tested were
relatively non-toxic to HepG2-C8 cells. The results of the DCFH-DA assay and
combination index (CI) indicated that quercetin, kaempferol, and pterostilbene
attenuated intracellular reactive oxygen species (ROS) levels when pretreated
individually and had synergistic effects when used in combination. In addition,
the combination treatment significantly induced ARE and increased the mRNA and
protein expression of Nrf2-regulated genes. Collectively, our study demonstrated
that the berry constituents quercetin, kaempferol, and pterostilbene activated
the Nrf2-ARE signaling pathway and exhibited synergistic anti-oxidative stress
activity at appropriate concentrations.
PMID- 25111661
TI - Metallothioneins attenuate paraquat-induced acute lung injury in mice through the
mechanisms of anti-oxidation and anti-apoptosis.
AB - Paraquat (PQ) is a widely used herbicide, and lung is the primary target of PQ
poisoning. Metallothionein (MT) is a potent antioxidant and free radical
scavenger, and has been shown to play a protective role in lung injury induced by
different stressors. This study was undertaken to evaluate the protective
potential of MT against PQ-induced acute lung injury using MT-I/II null (MT(-/-))
mice. Wild-type (MT(+/+)) mice and MT(-/-) mice were given one intragastric
administration of 50mg/kg PQ for 24h, and it was revealed that MT(-/-) mice were
more susceptible to PQ-induced acute lung injury than MT(+/+) mice evidenced by
the following findings. As compared with MT(+/+) mice, MT(-/-) mice presented
more severe histopathological lesions in the lung, higher pulmonary
malondialdehyde content, and more reduced pulmonary antioxidative enzymes
activities. PQ also induced more apoptosis in pneumocytes from MT(-/-) mice, and
the expressions of apoptosis-related proteins Bax, Bcl-2, cleaved-caspase-3, and
the ratio of Bax/Bcl-2 were all more significantly increased in PQ-treated MT(-/
) mice. Our results clearly demonstrate that endogenous MT can attenuate PQ
induced acute lung injury, possibly through the mechanisms of anti-oxidation and
anti-apoptosis.
PMID- 25111662
TI - Coordination of care between health and education systems for patients with a
hematologic or oncologic diagnosis: a time study analysis.
AB - Given the increasing emphasis on care coordination between healthcare and
schools, hospital-school liaison services are increasing in demand. Limited
research examines hospital-school liaison programs that focus on educational
journeys of school-age patients with a chronic illness. Thus, this initiative
aimed to determine the time needed to support the educational needs of these
patients. Liaisons tracked time spent per patient, and per specific task
category, to support school-age patients (N=419) using work-sampling and time-and
motion methods. Findings may be useful for hospital-based programs seeking to
establish or increase staff dedicated to the coordination of care between school
and healthcare systems.
PMID- 25111663
TI - Available resources and challenges for the clinical annotation of somatic
variations.
AB - Next-generation sequencing (NGS) has become an important tool for identifying
clinically relevant variants in both inherited disorders and oncology. Variants
annotation that enables the creation of meaningful clinical reports often
requires mining multiple publicly available databases. There are a number of such
resources that have been designed to catalog and mine a plethora of germline
variants or mutations. However, when analyzing tumor specimens in clinical
settings, one may need to use different or ancillary resources that are specific
for somatic variants or actionable mutations that may have clinical or treatment
implications. The purpose of this review is to recapitulate the state of the art
of somatic variation databases, which can aid in the clinical interpretation of
NGS-based assays in oncology. In addition, the current need for collating various
annotation sources into one-stop solutions to facilitate faster query execution
and better integration into existing laboratory information systems are
discussed.
PMID- 25111664
TI - On the precision of goal-directed attentional selection.
AB - Attention selects objects in a scene for cognitive processing. A growing body of
evidence has been used to argue that observers are able to narrowly restrict
attentional selection to stimuli that match a feature-based target template while
ignoring similar-looking distractors. For example, visual search for a target
among feature-similar nontargets is highly efficient. Here, I demonstrate that
observers are substantially impaired at selecting a target among feature-similar
nontargets when stimuli are compared with a target template serially in time. The
results argue that goal-directed attentional selection is distinctly imprecise,
and that comparing stimuli with a target template reflects an inefficient
mechanism of selection that cannot fully explain visual search performance under
demanding conditions.
PMID- 25111665
TI - Pitch structure, but not selective attention, affects accent weightings in
metrical grouping.
AB - Among other cues, pitch and temporal accents contribute to grouping in musical
sequences. However, exactly how they combine remains unclear, possibly because of
the role of structural organization. In 3 experiments, participants rated the
perceived metrical grouping of sequences that either adhered to the rules of
tonal Western musical pitch structure (musical key) or did not (atonal). The
tonal status of sequences did not provide any grouping cues and was irrelevant to
the task. Experiment 1 established equally strong levels of pitch leap accents
and duration accents in baseline conditions, which were then recombined in
subsequent experiments. Neither accent type was stronger or weaker for tonal and
atonal contexts. In Experiment 2, pitch leap accents dominated over duration
accents, but the extent of this advantage was greater when sequences were tonal.
Experiment 3 ruled out an attentional origin of this effect by replicating this
finding while explicitly manipulating attention to pitch or duration accents
between participant groups. Overall, the presence of tonal pitch structure made
the dimension of pitch more salient at the expense of time. These findings
support a dimensional salience framework in which the presence of organizational
structure prioritizes the processing of the more structured dimension regardless
of task relevance, independent from psychophysical difficulty, and impervious to
attentional allocation.
PMID- 25111666
TI - Selection history modulates the effects of dual mechanisms on flanker
interference.
AB - The limit of processing capacity and the effectiveness of top-down control are 2
mechanisms that underlie distractor interference in a flanker task. The current
study investigates how the interblock selection history shaped by the target
number and the predictability of distractor location may modulate the effects of
these 2 mechanisms on flanker interference. Experiment 1 showed that the
distractor compatibility effect was eliminated when the task array contained 4 or
5 identical targets, which reflected the capacity limit. The target number and
distractor location's predictability (Experiment 2) or location predictability
and target-distractor proximity (Experiment 3) were manipulated across blocks,
while compatibility varied within blocks, with control efficacy underlying the
effects of distractor location (predictability and proximity). The interblock
selection history was induced by task order, beginning with 2 or 4 targets in
Experiment 2 and with a distractor at a fixed or an unpredictable location in
Experiment 3. Effects of interblock selection history were found when the
intertrial context did not promote an incentive for altering the processing mode.
When the incentive for enacting top-down control is high, intertrial contextual
factors influence flanker interference. Contextual factors related to the target
number and distractor location modulate flanker interference at multiple levels.
PMID- 25111667
TI - A randomized, placebo-controlled, double-blind trial on the management of post
infective cough by inhaled ipratropium and salbutamol administered in
combination.
AB - Post-viral cough is a type of cough originating from upper respiratory tract
infections that persists after the infection is resolved. Although it was
hypothesized that bronchodilators might have a role in the management of post
viral cough, a clear demonstration of their efficacy is missing. Therefore, we
tested the efficacy of a combination of a beta-agonist and an anticholinergic
agent in reducing post-viral cough with a randomized, double blind, placebo
controlled clinical trial. Patients were treated for 10 days with either a
nebulized combination of salbutamol 1.875 mg/0.5 mL and ipratropium bromide 0.375
mg/0.5 mL, or a placebo, and followed up for another 10 days. Daytime and
nighttime cough severity and spirometry testing were assessed before starting
treatment, after 10 and 20 days. Ninety-two patients were randomized to receive
placebo (n = 46) or the active treatment (n = 46); nine of them (4 in the placebo
group, 5 in the active treatment group) dropped out from the study. Daytime and
nighttime cough severity were significantly reduced in both groups during the
study period, but the reduction was more prominent in the active treatment group
vs. placebo after 10 days of treatment (P = 0.003 for day cough; P = 0.061 for
night cough), whereas at the end of follow-up period cough severity was
comparable between the two groups. Small but significant increases in spirometric
parameters were observed in the active treatment vs. placebo group, although at
the end of follow-up these values returned to be comparable to placebo. The
frequency of adverse events was not significantly different between the two
groups of patients. We concluded that a combination of a beta-agonist and an
anticholinergic agent can effectively reduce post-viral cough, and can thus
represent a valid option for this type of cough.
PMID- 25111668
TI - Factors associated with postoperative hypothyroidism after lobectomy in papillary
thyroid microcarcinoma patients.
AB - PURPOSE: No previous study regarding the correlation between post-operative
thyroid function and underlying thyroid histopathology has been published. This
study assessed the relationship between postoperative thyroid function after
lobectomy and multiple factors in papillary thyroid microcarcinoma (PTMC)
patients. MATERIALS AND METHODS: From January 2010 to December 2010, 338 patients
who had undergone thyroid lobectomy for PTMC were enrolled. Patients with pre
operative hyperthyroidism or those with hypothyroidism but no pre-operative
serological data were excluded, leaving a cohort of 285 patients. The
relationships between post-operative thyroid function (based on successful
cessation of thyroxine replacement therapy) and multiple factors (patient age and
sex, serological data, the Pre-operative anteroposterior diameter of the thyroid
gland, underlying histopathology of the thyroid gland, and number of attempts to
stop thyroxine replacement therapy) were analyzed. RESULTS: Out of 285 patients,
157 attempted to stop thyroxine replacement therapy once or twice after
lobectomy; 91 successfully stopped thyroxine replacement therapy during the study
period. The final histopathologic diagnoses after surgery included Hashimoto's
thyroiditis (n = 5), non-Hashimoto type of lymphocytic thyroiditis (n = 17), and
normal thyroid parenchyma (n = 135). Pre-operative thyroid-stimulating hormone
(TSH) levels differed significantly between patients with postoperative
hypothyroidism and those with postoperative euthyroidism (univariate logistic
regression analysis, p = 0.0028; multivariate logistic regression analysis, p =
0.0029). No statistically significant differences were found for any other
factors. CONCLUSIONS: The study results demonstrated that the Pre-operative TSH
level was the only predictor for the development of post-operative hypothyroidism
after thyroid lobectomy in PTMC patients.
PMID- 25111669
TI - Synthesis of cyclic imides from nitriles and diols using hydrogen transfer as a
substrate-activating strategy.
AB - An atom-economical and versatile method for the synthesis of cyclic imides from
nitriles and diols was developed. The method utilizes a Ru-catalyzed transfer
hydrogenation reaction in which the substrates, diols, and nitriles are
simultaneously activated into lactones and amines in a redox-neutral manner to
afford the corresponding cyclic imides with evolution of H2 gas as the sole
byproduct. This operationally simple and catalytic synthetic method provides a
sustainable and easily accessible route to cyclic imides.
PMID- 25111670
TI - Maternal mood and concordant maternal and infant salivary cortisol during heel
lance while in kangaroo care.
AB - BACKGROUND: Maternal kangaroo care (MKC) is a naturalistic intervention that
alleviates neonatal pain, and mothers are assumed to play a stress regulatory
role in MKC. Yet, no MKC infant pain study has examined relationship between
maternal and infant stress reactivity concurrently, or whether post-partum
depression and/or anxiety (PPDA) alters maternal and neonatal stress response and
the regulatory effects of MKC. OBJECTIVES: To examine the concordance of salivary
cortisol reactivity between 42 mothers and their stable preterm infants during
routine infant heel lance (HL) while in MKC and to compare salivary cortisol
between groups of mothers with and without PPDA and their infants. METHODS:
Maternal and infant salivary cortisol samples were collected pre-HL and 20 min
post-HL with two additional maternal samples at night and in the morning. Mothers
and infants were allocated to with PPDA versus without PPDA study groups on the
basis of maternal post-natal mental health assessment scores. RESULTS: Higher
mothers' cortisol pre-HL was weakly associated with higher infants' salivary
cortisol in response to the HL procedure. Maternal depression and/or anxiety were
not associated with infants' cortisol. During HL, both groups of mothers and
infants showed no change in salivary cortisol. CONCLUSIONS: Concordance between
mother and infant salivary cortisol supports the maternal stress regulatory role
in MKC. MKC may have stress regulatory benefits for mothers and their preterm
infants during HL independent of PPDA. Future MKC studies that target mothers
with altered mood will help to build on these findings.
PMID- 25111673
TI - Implementation of a new screening recommendation in health care: the Veterans
Health Administration's approach to lung cancer screening.
PMID- 25111672
TI - Small regulatory RNAs in lambdoid bacteriophages and phage-derived plasmids: Not
only antisense.
AB - Until recently, only two small regulatory RNAs encoded by lambdoid bacteriophages
were known. These transcripts are derived from paQ and pO promoters. The former
one is supposed to act as an antisense RNA for expression of the Q gene, encoding
a transcription antitermination protein. The latter transcript, called oop RNA,
was initially proposed to have a double role, in establishing expression of the
cI gene and in providing a primer for DNA replication. Although the initially
proposed mechanisms by which oop RNA could influence the choice between two
alternative developmental pathways of the phage and the initiation of phage DNA
replication were found not true, the pO promoter has been demonstrated to be
important for both regulation of phage development and control of DNA
replication. Namely, the pO-derived transcript is an antisense RNA for expression
of the cII gene, and pO is a part of a dual promoter system responsible for
regulation of initiation of DNA synthesis from the orilambda region. Very recent
studies identified a battery of small RNAs encoded by lambdoid bacteriophages
existing as prophages in chromosomes of enterohemorrhagic Escherichia coli
strains. Some of them have very interesting functions, like anti-small RNAs.
PMID- 25111671
TI - The roles of microphthalmia-associated transcription factor and pigmentation in
melanoma.
AB - MITF and pigmentation play important roles in both normal melanocyte and
transformed melanoma cell biology. MITF is regulated by many pathways and it also
regulates many targets, some of which are still being discovered and functionally
validated. MITF is involved in a wide range of processes in melanocytes,
including pigment synthesis and lineage survival. Pigmentation itself plays an
important role as the interface between genetic and environmental factors that
contribute to melanoma.
PMID- 25111674
TI - Giant condyloma acuminatum in the axilla.
PMID- 25111675
TI - Cluster size effects of platinum oxide as active sites in hydrogen evolution
reactions.
AB - The successful design of photocatalytic hydrogen generation from water relies on
a thorough understanding of the role of cocatalyst. The photoreactivity was
studied as a function of the cluster size of the oxidized platinum cocatalyst.
The maximum turnover frequency is found on the smallest-sized cocatalyst. This
effect can be attributed to the size-dependent proton adsorption.
PMID- 25111676
TI - Redescription of Sarcocystis fusiformis sarcocysts from the water buffalo
(Bubalus bubalis).
AB - Four valid species of Sarcocystis have been reported from the water buffalo
(Bubalus bubalis): Sarcocystis fusiformis, Sarcocystis buffalonis, Sarcocystis
levinei and Sarcocystis dubeyi. Here, we redescribe structure of S. fusiformis
sarcocysts by scanning and transmission electron microscopy (SEM, TEM). Twenty
one macroscopic sarcocysts from oesophagus of the water buffalo in Egypt were
examined by light microscopy, SEM and TEM. The sarcocyst wall was up to 9 MUm
thick, depending on the section and the technique. In 5 MUm paraffin-embedded
sections, the sarcocyst wall was indistinct, 2-5 MUm thick and appeared smooth.
In 1 MUm plastic-embedded sections stained with toluidine blue, the sarcocyst
wall was 2.5-5.2 MUm thick and had branched villar protrusions (vp)-like branches
of a dead tree. By SEM, the sarcocyst wall had a mesh-like structure with
irregularly shaped vp that were folded over the sarcocyst wall. On each vp there
were uniform papillomatous structures that were 100 nm wide. By TEM, vp were up
to 6 MUm long and contained filamentous tubular structures, most of which were
parallel to the long axis of the projections; granules were absent from these
tubules. By TEM, bradyzoites within the same cyst varied from 11.2 to 16.8 MUm in
length. By TEM, bradyzoites had a very long (10 MUm) convoluted mitochondrion, up
to 12 dense granules, but only 2 rhoptries. This redescription should help to
differentiate the sarcocysts of S. fusiformis from similar sarcocysts in domestic
and wild ruminants.
PMID- 25111677
TI - A superhydrophobic chip based on SU-8 photoresist pillars suspended on a silicon
nitride membrane.
AB - We developed a new generation of superhydrophobic chips optimized for probing
ultrasmall sample quantities by X-ray scattering and fluorescence techniques. The
chips are based on thin Si3N4 membranes with a tailored pattern of SU-8
photoresist pillars. Indeed, aqueous solution droplets can be evaporated and
concentrated at predefined positions using a non-periodic pillar pattern. We
demonstrated quantitatively the deposition and aggregation of gold
glyconanoparticles from the evaporation of a nanomolar droplet in a small spot by
raster X-ray nanofluorescence. Further, raster nanocrystallography of biological
objects such as rod-like tobacco mosaic virus nanoparticles reveals crystalline
macro-domain formation composed of highly oriented nanorods.
PMID- 25111678
TI - SUMO1 genetic polymorphisms may contribute to the risk of nonsyndromic cleft lip
with or without palate: a meta-analysis.
AB - OBJECTIVE: We conducted the present meta-analysis to investigate whether single
nucleotide polymorphisms (SNPs) in the SUMO1 gene contribute to the risk of
nonsyndromic cleft lip with or without palate (NSCL/P). METHOD: The Web of
Science (1945-2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966
2013), EMBASE (1980-2013), CINAHL (1982-2013), and the Chinese Biomedical
Database (CBM) (1982-2013) were searched without language restrictions. Meta
analysis was performed with the use of the STATA statistical software. RESULTS:
Six studies with a total of 1381 NSCL/P patients and 2054 control subjects were
included. Twenty-seven functional polymorphisms in the SUMO1 gene were assessed.
Our results indicated that SUMO1 genetic polymorphisms were correlated with an
increased risk of NSCL/P. Subgroup analysis by the SNP type indicated that 4
functional polymorphisms (rs12470401 T>C, rs16838917 A>G, rs12470529 A>G, and
rs7572505 A>G) in the SUMO1 gene might be strongly correlated with NSCL/P risk.
Furthermore, ethnicity-stratified analysis demonstrated that SUMO1 genetic
polymorphisms were closely related to an increased risk of NSCL/P among both
Asians and Caucasians. CONCLUSION: Our findings provide empirical evidence that
SUMO1 genetic polymorphisms might be strongly involved in the etiology of NSCL/P,
especially for rs12470401 T>C, rs16838917 A>G, rs12470529 A>G, and rs7572505 A>G
polymorphisms.
PMID- 25111679
TI - Posterior reversible encephalopathy syndrome: An atypical complication of
postpartum wound infection.
PMID- 25111680
TI - Fluid removal in acute heart failure: diuretics versus devices.
AB - PURPOSE OF REVIEW: Fluid removal and relief of congestion are central to
treatment of acute heart failure. Diuretics have been the decongestive mainstay
but their known limitations have led to the exploration of alternative
strategies. This review compares diuretics with ultrafiltration and examines the
recent evidence evaluating their use. RECENT FINDINGS: Relevant recent studies
are the Diuretic Optimization Strategies Evaluation trial (of diuretics) and the
Cardiorenal Rescue Study in Acute Decompensated Heart Failure (of
ultrafiltration). The Diuretic Optimization Strategies Evaluation study evaluated
strategies of loop diuretic use during acute heart failure (continuous infusion
versus intermittent bolus and high dose versus low dose). After 72 h, there was
no significant difference with either comparison for the coprimary end points.
Patients treated with a high-dose strategy tended to have greater diuresis and
more decongestion compared with low-dose therapy, at the cost of transient
changes in renal function. The Cardiorenal Rescue Study in Acute Decompensated
Heart Failure study showed that in acute heart failure patients with persistent
congestion and worsening renal function, ultrafiltration, as compared with a
medical therapy, was associated with similar weight loss but greater increase in
serum creatinine and more adverse events. SUMMARY: Decongestion remains a major
challenge in acute heart failure. Although recent studies provide useful data to
guide practice, the relatively poor outcomes point to the continued need to
identify better strategies for safe and effective decongestion.
PMID- 25111681
TI - Theoretical explanation of the photoswitchable superhydrophobicity of
diarylethene microcrystalline surfaces.
AB - Two types of superhydrophobic surfaces which show lotus and petal effects were
induced on photochromic diarylethene microcrystalline surfaces by UV and visible
light irradiation and temperature control. On the surfaces showing the lotus
effect, a low-adhesion superhydrophobic property is attributed to the surface
structure being covered with densely standing needle-shaped crystals of the
closed-ring isomer. On surfaces showing the petal effect, a high-adhesion
superhydrophobic surface consists of fine needle-shaped crystals with high
density together with a few rod-shaped crystals, where an invasion phenomenon
occurs between these rod-shaped crystals. Furthermore, the different
superhydrophobic properties of the surfaces are theoretically explained using
multipillar surface models.
PMID- 25111683
TI - The value of preoperative medical testing for vitreoretinal surgery.
AB - PURPOSE: To determine whether preoperative medical testing reduces the risk of
postoperative systemic adverse events after vitreoretinal surgery. METHODS:
Retrospective cohort study at a single academic university hospital involving a
total of 2,215 patients undergoing vitreoretinal surgery. Medical charts of 2,215
patients who underwent vitreoretinal surgery between January 2002 and November
2011 at Vanderbilt University were reviewed for baseline comorbidities,
preoperative testing, type of anesthesia during surgery, and systemic adverse
events occurring within 30 days after surgery. Main outcome measures were the
association of baseline characteristics and preoperative testing with
postoperative systemic adverse events. RESULTS: Approximately a half of patients
had electrolyte, renal function, and electrocardiogram evaluation. The most
common comorbidities were hypertension (53%), diabetes mellitus (37%), and
coronary artery disease (18%). The most common preoperative testing performed was
blood glucose (58%). A total of 102 systemic adverse events occurred in 89 of
2,215 patients (4%) within the first 30 days after surgery with the majority
(72%) occurring within the first 24 hours. The most common adverse event was
bradycardia (34%) followed by desaturation (25%). Patients with a history of
coronary artery disease, asthma, chronic renal disease, or receiving general
anesthesia had a 2.04 (P = 0.01), 2.18 (P = 0.03), 2.76 (P < 0.01), and 3.72 (P <
0.001) increased odds of developing postoperative systemic adverse events,
respectively. Multivariate logistic regression analysis demonstrated no
significant correlation between preoperative testing and postoperative adverse
events. CONCLUSION: Incidence of postoperative systemic adverse events after
vitreoretinal surgery was 4% and was significantly increased in patients with
coronary artery disease, asthma, chronic renal disease, or receiving general
anesthesia. In this series, preoperative testing did not measurably influence
rates of postoperative systemic complications.
PMID- 25111682
TI - Expression of receptor activator of nuclear factor kappa-B as a poor prognostic
marker in breast cancer.
AB - PURPOSE: Receptor activator of nuclear factor kappa-B and its ligand (RANK/RANKL)
and Osteoprotegerin (OPG) are key molecules for regulating osteoclastic activity
in bone. However, little is known about the role of RANK-related molecules in
breast cancer prognosis. We aimed to evaluate RANK, RANKL, and OPG expression and
the associated clinical impact in breast cancer. METHODS: Tissue microarray (TMA)
from 185 patients with primary breast cancer was established.
Immunohistochemistry for RANK, RANKL, and OPG was performed. Clinicopathologic
features and survival outcomes associated with expression of RANK, RANKL, and OPG
were analyzed. RESULTS: RANK, RANKL, and OPG were expressed in 74.1%, 78.4%, and
45.9% of patients, respectively. RANKL expression was associated with lower Ki-67
level. OPG expression was related to small tumor size, node negativity, and low
Ki-67. There was no significant difference in clinicopathologic features between
tumors with RANK and those without RANK. RANK expression was significantly
associated with poor disease-free survival in univariate analysis (P = 0.04) and
multivariate analysis (P = 0.02). RANKL expression was associated with improved
skeletal disease-free survival in multivariate analysis (P = 0.03). CONCLUSIONS:
The RANK/RANKL pathway regulated by OPG may have a role in predicting progression
and prognosis of breast cancer.
PMID- 25111684
TI - Diagnostic and Therapeutic Challenges.
PMID- 25111685
TI - Malattia leventinese/Doyne honeycomb retinal dystrophy in a chinese family with
mutation of the EFEMP1 gene.
AB - PURPOSE: To characterize the clinical features and molecular genetic findings in
a Chinese pedigree with Malattia leventinese/Doyne honeycomb retinal dystrophy.
METHODS: All patients underwent ophthalmologic examinations, including Snellen
best-corrected visual acuity, fundus photography, fundus autofluorescence
imaging, fundus fluorescein angiography, and optical coherence tomography.
Genomic DNA was isolated from blood samples. All exons of EFEMP1 were amplified
by polymerase chain reaction and sequenced. Possible structural and functional
impacts of the protein because of amino acid substitution were predicted by
bioinformatics analysis. RESULTS: A heterozygous missense mutation comprising C >
T in exon 10 of EFEMP1 was identified in all patients of the pedigree; this
resulted in an amino acid substitution at position 345 (Arg345Trp, R345W).
Clinically, six patients from the Chinese family were ascertained with varying
degrees of early onset drusen. Besides the drusen, choroidal neovascularization
and retinal pigment epithelium changes were noted in some patients. Increased
autofluorescence corresponding to the drusen was detected in the R345W mutation
patients. Intrafamilial patients with Malattia leventinese/Doyne honeycomb
retinal dystrophy seem to be phenotypically variable in visual loss,
ophthalmoscopic findings, autofluorescence imaging, and optical coherence
tomography changes. The amino acid change may have an effect on protein structure
and function through bioinformatics analysis. CONCLUSION: The R345W mutation in
EFEMP1 caused Malattia leventinese/Doyne honeycomb retinal dystrophy in a Chinese
family. This is the first report, as per our knowledge, of the R345W mutation in
EFEMP1 in a Chinese pedigree of this disease.
PMID- 25111686
TI - Neuroprotective effects of intravitreal triamcinolone acetonide and dexamethasone
implant in rabbit retinas after pars plana vitrectomy and silicone oil injection.
AB - PURPOSE: To investigate potential retinal neuroprotective effects of intravitreal
triamcinolone acetonide and dexamethasone implant in rabbits after pars plana
vitrectomy and intravitreal silicone oil injection. METHODS: The right eyes of 84
rabbits, divided into 3 groups of 28 rabbits each, underwent standard 3-port pars
plana vitrectomy with silicone oil (SO group), silicone oil and intravitreal
dexamethasone implant (SO/DEX group), or silicone oil and triamcinolone acetonide
(SO/TA group). The retina from the left eye of each rabbit served as a control.
The animals were killed at 4 weeks after surgery. Qualitative and quantitative
histopathologic analyses were performed 4 weeks after surgery, and investigation
for apoptosis was performed using the Tunel assay. RESULTS: Intravitreal
triamcinolone acetonide and dexamethasone implant were associated with increased
retinal neuronal survival, primarily in the outer nuclear layer, inner nuclear
layer, and ganglion cell layer. In the SO group, the cell density in eyes that
underwent PPV/SO was 31% lower in the outer nuclear layer, 33% lower in the inner
nuclear layer, and 45% lower in the ganglion cell layer compared to control eyes
(p < 0.05 for all PPV/SO versus control comparisons). Compared to eyes that
underwent PPV/SO, the cell density in eyes treated with triamcinolone was 27%
higher in the outer nuclear layer, 66% higher in the inner nuclear layer, and
100% higher in the ganglion cell layer (p < 0.05 for all triamcinolone versus
PPV/SO comparisons). Compared to eyes that underwent PPV/SO, the cell density in
eyes treated with dexamethasone was 46% higher in the outer nuclear layer, 62%
higher in the inner nuclear layer, and 77% higher in the ganglion cell layer (p <
0.05 for all dexamethasone versus PPV/SO comparisons). Analyses using the Tunnel
assay demonstrated apoptotic bodies in all eyes in the SO group, compared with
none of the eyes in the SO/TA and SO/DEX groups. The presence of cell nuclei
stained with 49,6-diamidino-2-phenylindole (DAPI) was demonstrated in all groups.
CONCLUSION: In this experimental model of neuroprotection, increased retinal
neuronal survival was seen in the steroid-treated groups compared with the
controls.
PMID- 25111687
TI - Posterior scleral reinforcement and vitrectomy for myopic foveoschisis in extreme
myopia.
AB - PURPOSE: To evaluate the effect of surgical posterior scleral reinforcement in
extremely myopic patients (axial length >=30 mm) with myopic foveoschisis.
METHODS: The retrospective interventional case series study included patients
with an axial length >=30 mm, posterior scleral staphyloma, and myopic
foveoschisis, who were treated either by posterior scleral reinforcement and 23
gauge 3-port pars plana vitrectomy (posterior scleral reinforcement group) or by
vitrectomy (vitrectomy group) alone. All eyes additionally underwent cataract
surgery. RESULTS: The study included 28 patients (28 eyes) with no significant
(all P > 0.05) difference between the posterior scleral reinforcement group (n =
14) and the vitrectomy group (n = 14) in age, refractive error, axial length, and
preoperative best-corrected visual acuity (BCVA). In addition to posterior
scleral staphyloma and foveoschisis, a macular hole, a macular hole-associated
retinal detachment, and a macular detachment without macular hole were present in
three eyes, five eyes, and one eye, respectively in the study group and in three
eyes, three eyes, and six eyes, respectively in the control group. In the study
group, BCVA was significantly better after surgery than at baseline (P = 0.005)
with an improvement in BCVA in 13 eyes, whereas BCVA was unchanged in 1 eye. In
the control group, BCVA at baseline and at the end of follow-up did not differ
significantly (P = 0.22). Gain in BCVA was marginally significantly higher in the
study group than that in the control group (improvement by 0.69 +/- 0.76 logMAR
vs. 0.19 +/- 0.54 logMAR; P = 0.05). The number of eyes with any improvement in
BCVA (13 [93%] eyes vs. 11 [79%] eyes; P = 0.289) did not differ between both
groups; an improvement in BCVA by more than 2 lines (10 [71%] eyes vs. 3 [21%]
eyes; P = 0.009) was significantly higher in the study group than that in the
control group. Anatomical success (defined as closure of macular holes and
collapse of the foveoschisis) was achieved earlier in the study group (3.7 +/-
3.2 months vs. 6.2 +/- 3.0 months; P = 0.04). CONCLUSION: Posterior scleral
reinforcement in association with vitrectomy, as compared with vitrectomy alone,
was associated with a higher improvement in visual acuity in extremely myopic
eyes with foveoschisis.
PMID- 25111688
TI - The cost of being queen: investment across Pogonomyrmex harvester ant gynes that
differ in degree of claustrality.
AB - The role of the ant colony largely consists of non-reproductive tasks, such as
foraging, tending brood, and defense. However, workers are vitally linked to
reproduction through their provisioning of sexual offspring, which are produced
annually to mate and initiate new colonies. Gynes (future queens) have size
associated variation in colony founding strategy (claustrality), with each
strategy requiring different energetic investments from their natal colony. We
compared the per capita production cost required for semi-claustral, facultative,
and claustral gynes across four species of Pogonomyrmex harvester ants. We found
that the claustral founding strategy is markedly expensive, costing approximately
70% more energy than that of the semi-claustral strategy. Relative to males,
claustral gynes also had the largest differential investment and smallest size
variation. We applied these investment costs to a model by Brown and Bonhoeffer
(2003) that predicts founding strategy based on investment cost and foraging
survivorship. The model predicts that non-claustral foundresses must survive the
foraging period with a probability of 30-36% in order for a foraging strategy to
be selectively favored. These results highlight the importance of incorporating
resource investment at the colony level when investigating the evolution of
colony founding strategies in ants.
PMID- 25111689
TI - Control of larval and egg development in Aedes aegypti with RNA interference
against juvenile hormone acid methyl transferase.
AB - RNA interference (RNAi) is a powerful approach for elucidating gene functions in
a variety of organisms, including mosquitoes and many other insects. Little has
been done, however, to harness this approach in order to control adult and larval
mosquitoes. Juvenile hormone (JH) plays a pivotal role in the control of
reproduction in adults and metamorphism in larval mosquitoes. This report
describes an approach to control Aedes aegypti using RNAi against JH acid methyl
transferase (AeaJHAMT), the ultimate enzyme in the biosynthetic pathway of JH III
that converts JH acid III (JHA III) into JH III. In female A. aegypti that were
injected or fed jmtA dsRNA targeting the AeaJHAMT gene (jmtA) transcript, egg
development was inhibited in 50% of the treated females. In mosquito larvae that
were fed transgenic Pichia pastoris cells expressing long hair pin (LHP) RNA,
adult eclosion was delayed by 3 weeks causing high mortality. Northern blot
analyses and qPCR studies show that jmtA dsRNA causes inhibition of jmtA
transcript in adults and larvae, which is consistent with the observed inhibition
of egg maturation and larval development. Taken together, these results suggest
that jmtA LHP RNA expressed in heat inactivated genetically modified P. pastoris
cells could be used to control mosquito populations in the marsh.
PMID- 25111690
TI - Uric acid induces fat accumulation via generation of endoplasmic reticulum stress
and SREBP-1c activation in hepatocytes.
AB - Non-alcoholic fatty liver disease (NAFLD) is currently one of the most common
types of chronic liver injury. Elevated serum uric acid is a strong predictor of
the development of fatty liver as well as metabolic syndrome. Here we demonstrate
that uric acid induces triglyceride accumulation by SREBP-1c activation via
induction of endoplasmic reticulum (ER) stress in hepatocytes. Uric acid-induced
ER stress resulted in an increase of glucose-regulated protein (GRP78/94),
splicing of the X-box-binding protein-1 (XBP-1), the phosphorylation of protein
kinase RNA-like ER kinase (PERK), and eukaryotic translation initiation factor
2alpha (eIF-2alpha) in cultured hepatocytes. Uric acid promoted hepatic
lipogenesis through overexpression of the lipogenic enzyme, acetyl-CoA
carboxylase 1 (ACC1), fatty acid synthase (FAS), and stearoyl-CoA desaturase 1
(SCD1) via activation of SREBP-1c, which was blocked by probenecid, an organic
anion transport blocker in HepG2 cells and primary hepatocytes. A blocker of ER
stress, tauroursodeoxycholic acid (TUDCA), and an inhibitor of SREBP-1c,
metformin, blocked hepatic fat accumulation, suggesting that uric acid promoted
fat synthesis in hepatocytes via ER stress-induced activation of SREBP-1c. Uric
acid-induced activation of NADPH oxidase preceded ER stress, which further
induced mitochondrial ROS production in hepatocytes. These studies provide new
insights into the mechanisms by which uric acid stimulates fat accumulation in
the liver.
PMID- 25111693
TI - A hydrophobic hole transporting oligothiophene for planar perovskite solar cells
with improved stability.
AB - An oligothiophene derivative named DR3TBDTT with high hydrophobicity was
synthesized and functioned as the hole transporting material without an ion
additive. 8.8% of power conversion efficiency was obtained for CH3NH3PbI3-xClx
based planar solar cells with improved stability, compared to devices using Li
TFSI doped spiro-MeOTAD.
PMID- 25111692
TI - Renoprotective effect of red ginseng in gentamicin-induced acute kidney injury.
AB - Aminoglycoside-induced nephrotoxicity is one of the prevalent causes of acute
kidney injury (AKI). Oxidative stress-mediated apoptosis of renal tubular cells
is known to be a major mechanism of renal injury. Red ginseng extract (RGE) has
been reported to possess antioxidant and immune-modulatory activities. We
investigated the effect of RGE on gentamicin (GM)-induced apoptosis and oxidative
stress in cultured renal tubular cells and animal model of GM-induced AKI. GM
induced the generation of reactive oxygen species (ROS) with an increase in NADPH
oxidase (NOX) activity and mitochondrial oxidation in NRK-52E cells that were
ameliorated with RGE. GM-induced apoptosis of NRK-52E cells, which was associated
with an increased expression of mitochondrial Bax, cytosolic cytochrome c, and
cleaved caspase-9 and -3, along with a decrease in bcl-2 expression, was also
blocked by RGE. In an animal model of GM-induced AKI, RGE treatment significantly
attenuated renal dysfunction, cell apoptosis, and tubular damage. RGE ameliorated
ROS production in rats with GM-induced AKI, as demonstrated by an increase in the
reduced form of glutathione in renal cortex and a decrease in urinary excretion
of 8-hydroxy-2'-deoxyguanosine. Our results suggest that RGE protects the kidney
from GM-induced AKI via the mechanism of modulation of oxidative stress.
PMID- 25111694
TI - Highlighting the importance of metabolic risk factors, obesity, and liver
steatosis after pediatric liver transplantation.
PMID- 25111691
TI - Merkel cell carcinoma expresses vasculogenic mimicry: demonstration in patients
and experimental manipulation in xenografts.
AB - Merkel cell carcinoma (MCC) is a highly virulent cutaneous neoplasm that, like
melanoma, is a frequent cause of patient morbidity and mortality. The cellular
mechanisms responsible for the aggressive behavior of MCC remain unknown.
Vasculogenic mimicry (VM) is a phenomenon associated with cancer virulence,
including in melanoma, whereby anastomosing laminin networks form in association
with tumor cells that express certain endothelial genes. To determine whether VM
is a factor in MCC, we employed a relevant xenograft model using two independent
human MCC lines. Experimentally induced tumors were remarkably similar
histologically to patient MCC, and both contained laminin networks associated
with vascular endothelial-cadherin (CD144) and vascular endothelial growth factor
receptor 1, as well as Nodal expression typical of VM in melanoma. Moreover, two
established chemotherapeutic agents utilized for human MCC, etoposide and
carboplatin, induced necrosis in xenografts on systemic administration while
enriching for laminin networks in apparently resistant viable tumor regions that
persisted. These findings for the first time establish VM-like laminin networks
as a biomarker in MCC, demonstrate the experimental utility of the MCC xenograft
model, and suggest that VM-rich regions of MCC may be refractory to conventional
chemotherapeutic agents.
PMID- 25111696
TI - Gift-giving and network structure in rural China: utilizing long-term spontaneous
gift records.
AB - The tradition of keeping written records of gift received during household
ceremonies in many countries offers researchers an underutilized means of data
collection for social network analysis. This paper first summarizes unique
features of the gift record data that circumvent five prevailing sampling and
measurement issues in the literature, and we discuss their advantages over
existing studies at both the individual level and the dyadic link level using
previous data sources. We then document our research project in rural China that
implements a multiple wave census-type household survey and a long-term gift
record collection. The pattern of gift-giving in major household social events
and its recent escalation is analyzed. There are significantly positive
correlations between gift network centrality and various forms of informal
insurance. Finally, economic inequality and competitive marriage market are among
the main demographic and socioeconomic determinants of the observed gift network
structure.
PMID- 25111698
TI - Validation of a high throughput flow cytometric in vitro micronucleus assay
including assessment of metabolic activation in TK6 cells.
AB - Genotoxicity is an unacceptable property for new drug candidates and we employ
three screening assays during the drug discovery process to identify genotoxicity
early and optimize chemical series. One of these methods is the flow cytometric
in vitro micronucleus assay for which protocol optimizations have been described
recently. Here, we report further validation of the assay in TK6 cells including
assessment of metabolic activation. We first optimized assay conditions to allow
for testing with and without metabolic activation in parallel in a 96-well plate
format. Then, we tested a set of 48 compounds carefully selected to contain known
in vivo genotoxins, nongenotoxins and drugs. Avoidance of irrelevant positives, a
known issue with mammalian cell-based genotoxicity assays, is important to
prevent early deselection of potentially promising compounds. Therefore, we
enriched the validation set with compounds that were previously reported to
produce irrelevant positive results in mammalian cell-based genotoxicity assays.
The resulting dataset was used to set the relevant cut-off values for scoring a
compound positive or negative, such that we obtained an optimal balance of high
sensitivity (88%) and high specificity (87%). Finally, we tested an additional
set of 16 drugs to further probe assay performance and 14 of them were classified
correctly. To our knowledge, the present study is the most comprehensive
validation of the in vitro flow cytometric micronucleus assay and the first to
report parallel assessment with metabolic activation in reasonable throughput.
The assay allows for rapidly screening novel compounds for genotoxicity and is
therefore well-suited for use in early drug discovery projects. Environ.
PMID- 25111695
TI - Involvement of potato (Solanum tuberosum L.) MKK6 in response to potato virus Y.
AB - Mitogen-activated protein kinase (MAPK) cascades have crucial roles in the
regulation of plant development and in plant responses to stress. Plant
recognition of pathogen-associated molecular patterns or pathogen-derived
effector proteins has been shown to trigger activation of several MAPKs. This
then controls defence responses, including synthesis and/or signalling of defence
hormones and activation of defence related genes. The MAPK cascade genes are
highly complex and interconnected, and thus the precise signalling mechanisms in
specific plant-pathogen interactions are still not known. Here we investigated
the MAPK signalling network involved in immune responses of potato (Solanum
tuberosum L.) to Potato virus Y, an important potato pathogen worldwide. Sequence
analysis was performed to identify the complete MAPK kinase (MKK) family in
potato, and to identify those regulated in the hypersensitive resistance response
to Potato virus Y infection. Arabidopsis has 10 MKK family members, of which we
identified five in potato and tomato (Solanum lycopersicum L.), and eight in
Nicotiana benthamiana. Among these, StMKK6 is the most strongly regulated gene in
response to Potato virus Y. The salicylic acid treatment revealed that StMKK6 is
regulated by the hormone that is in agreement with the salicylic acid-regulated
domains found in the StMKK6 promoter. The involvement of StMKK6 in potato defence
response was confirmed by localisation studies, where StMKK6 accumulated strongly
only in Potato-virus-Y-infected plants, and predominantly in the cell nucleus.
Using a yeast two-hybrid method, we identified three StMKK6 targets downstream in
the MAPK cascade: StMAPK4_2, StMAPK6 and StMAPK13. These data together provide
further insight into the StMKK6 signalling module and its involvement in plant
defence.
PMID- 25111699
TI - Assembly of polyelectrolyte multilayer films on supported lipid bilayers to
induce neural stem/progenitor cell differentiation into functional neurons.
AB - The key factors affecting the success of neural engineering using neural
stem/progenitor cells (NSPCs) are the neuron quantity, the guidance of neurite
outgrowth, and the induction of neurons to form functional synapses at synaptic
junctions. Herein, a biomimetic material comprising a supported lipid bilayer
(SLB) with adsorbed sequential polyelectrolyte multilayer (PEM) films was
fabricated to induce NSPCs to form functional neurons without the need for serum
and growth factors in a short-term culture. SLBs are suitable artificial
substrates for neural engineering due to their structural similarity to synaptic
membranes. In addition, PEM film adsorption provides protection for the SLB as
well as the ability to vary the surface properties to evaluate the effects of
physical and mechanical signals on NSPC differentiation. Our results revealed
that NSPCs were inducible on SLB-PEM films consisting of up to eight alternating
layers. In addition, the process outgrowth length, the percentage of
differentiated neurons, and the synaptic function were regulated by the number of
layers and the surface charge of the outermost layer. The average process
outgrowth length was greater than 500 MUm on SLB-PLL/PLGA (n = 7.5) after only 3
days of culture. Moreover, the quantity and quality of the differentiated neurons
were obviously enhanced on the SLB-PEM system compared with those on the PEM-only
substrates. These results suggest that the PEM films can induce NSPC adhesion and
differentiation and that an SLB base may enhance neuron differentiation and
trigger the formation of functional synapses.
PMID- 25111700
TI - Automated movement correction for dynamic PET/CT images: evaluation with phantom
and patient data.
AB - Head movement during a dynamic brain PET/CT imaging results in mismatch between
CT and dynamic PET images. It can cause artifacts in CT-based attenuation
corrected PET images, thus affecting both the qualitative and quantitative
aspects of the dynamic PET images and the derived parametric images. In this
study, we developed an automated retrospective image-based movement correction
(MC) procedure. The MC method first registered the CT image to each dynamic PET
frames, then re-reconstructed the PET frames with CT-based attenuation
correction, and finally re-aligned all the PET frames to the same position. We
evaluated the MC method's performance on the Hoffman phantom and dynamic FDDNP
and FDG PET/CT images of patients with neurodegenerative disease or with poor
compliance. Dynamic FDDNP PET/CT images (65 min) were obtained from 12 patients
and dynamic FDG PET/CT images (60 min) were obtained from 6 patients. Logan
analysis with cerebellum as the reference region was used to generate regional
distribution volume ratio (DVR) for FDDNP scan before and after MC. For FDG
studies, the image derived input function was used to generate parametric image
of FDG uptake constant (Ki) before and after MC. Phantom study showed high
accuracy of registration between PET and CT and improved PET images after MC. In
patient study, head movement was observed in all subjects, especially in late PET
frames with an average displacement of 6.92 mm. The z-direction translation
(average maximum = 5.32 mm) and x-axis rotation (average maximum = 5.19 degrees)
occurred most frequently. Image artifacts were significantly diminished after MC.
There were significant differences (P<0.05) in the FDDNP DVR and FDG Ki values in
the parietal and temporal regions after MC. In conclusion, MC applied to dynamic
brain FDDNP and FDG PET/CT scans could improve the qualitative and quantitative
aspects of images of both tracers.
PMID- 25111701
TI - Argument structure and the representation of abstract semantics.
AB - According to the dual coding theory, differences in the ease of retrieval between
concrete and abstract words are related to the exclusive dependence of abstract
semantics on linguistic information. Argument structure can be considered a
measure of the complexity of the linguistic contexts that accompany a verb. If
the retrieval of abstract verbs relies more on the linguistic codes they are
associated to, we could expect a larger effect of argument structure for the
processing of abstract verbs. In this study, sets of length- and frequency
matched verbs including 40 intransitive verbs, 40 transitive verbs taking simple
complements, and 40 transitive verbs taking sentential complements were presented
in separate lexical and grammatical decision tasks. Half of the verbs were
concrete and half were abstract. Similar results were obtained in the two tasks,
with significant effects of imageability and transitivity. However, the
interaction between these two variables was not significant. These results
conflict with hypotheses assuming a stronger reliance of abstract semantics on
linguistic codes. In contrast, our data are in line with theories that link the
ease of retrieval with availability and robustness of semantic information.
PMID- 25111702
TI - Lewis acid mediated tandem reaction of propargylic alcohols to tetrazoles
involving C-O- and C-C-bond cleavage reactions and a C-N-bond formation.
AB - A novel and direct synthesis of 1-aryl-5-arylvinyl-tetrazoles from easily
prepared propargylic alcohols and TMSN3 is developed in the presence of TMSCl
under mild conditions (TMS = trimethylsilyl). The process involves an
allenylazide intermediate, followed by a C-C-bond cleavage and C-N-bond formation
to afford the desired products. Moreover, this method offers a good functional
group applicability and can be scaled-up to grams (yield up to 85 %).
PMID- 25111703
TI - Perfectionism, neuroticism, and daily stress reactivity and coping effectiveness
6 months and 3 years later.
AB - The present study addressed a fundamental gap between research and clinical work
by advancing longitudinal explanatory conceptualizations of stress and coping
processes that trigger daily affect in the short- and long-term for individuals
with higher levels of personality vulnerability. Community adults completed
measures of 2 higher order dimensions of perfectionism (personal standards [PS],
self-criticism [SC]), neuroticism, and conscientiousness. Then, 6 months later
and again 3 years later, participants completed daily questionnaires of stress,
coping, and affect for 14 consecutive days. PS was associated with aggregated
daily problem-focused coping and positive reinterpretation, whereas SC was
uniquely associated with daily negative social interactions, avoidant coping,
negative affect, and sadness at Month 6 and Year 3. Multilevel modeling results
demonstrated that both individuals with higher PS and those with higher SC were
emotionally reactive to event stress, negative social interactions, and avoidant
coping at Month 6 and Year 3 and to less perceived control at Year 3. Positive
reinterpretation was especially effective for individuals with higher SC at Month
6 and Year 3. The effects of PS on daily stress reactivity and coping
(in)effectiveness were clearly distinguished from the effects of neuroticism and
conscientiousness, whereas the SC effects were due to shared overlap with PS and
neuroticism. The present findings demonstrate the promise of using repeated daily
diary methodologies to help therapists and clients reliably predict future client
reactions to daily stressors, which, in turn, could help guide interventions to
break apart dysfunctional patterns connected to distress and build resilience for
vulnerable individuals.
PMID- 25111704
TI - Predicting job satisfaction: a new perspective on person-environment fit.
AB - There may be 2 ways to look at person-environment (P-E) fit: the extent to which
the environment matches the person (which, in the case of person-job [P-J] fit,
we term ideal-job actualization) and the extent to which the person matches the
environment (which we term actual-job regard; cf. Hardin & Larsen, 2014). Adults
employed full time in the United States (n = 251; 49.8% women) completed an
online survey that included measures assessing these 2 perspectives on P-J fit,
along with measures of job and life satisfaction. Ideal-job actualization and
actual-job regard were empirically and conceptually distinct, each accounting for
unique variance in overall job satisfaction, even after controlling for overall
life satisfaction and remuneration. Looking at fit from these 2 frames of
reference may give a more complete perspective that accounts for critical
outcomes, like satisfaction, as well as suggest novel approaches to career
counseling.
PMID- 25111705
TI - Classification challenges in perfectionism.
AB - High performance expectations are central to perfectionism, but because most
participants endorse high standards, it becomes difficult for practitioners and
researchers to accurately screen for perfectionists. We addressed problems linked
to the measurement and classification of perfectionism by testing various
strategies aimed at broadening the range and skew of scores on the Standards
subscale from the Almost Perfect Scale-Revised (APS-R; Slaney, Mobley, Trippi,
Ashby, & Johnson, 1996). Randomly assigned participants (N = 506) completed the
APS-R following standard instructions or 1 of 2 variations, one prompting
participants to consider their responses in light of a normal distribution of
scores and another in which participants used a visual analog (slider) scale. The
visual analog scale produced more differentiated scores, but range restrictions
and skewed distributions remained for all 3 variations. Statistical
transformations improved skew. Factor mixture modeling was conducted using
transformed and nontransformed perfectionism scores along with criterion
indicators of emotion regulation (reappraisal or suppression), perceived stress,
and depression. Results supported a 3-class model, although more balanced
distributions of classes emerged than were previously reported. Perfectionists
were differentiated from nonperfectionists by their higher standards scores.
Maladaptive perfectionists scored highest among the classes on most self-critical
perfectionism indicators, suppression, perceived stress, and depression. Adaptive
perfectionists had the lowest levels of perceived stress and depression and
scored highest on reappraisal. Both perfectionist classes had generally
comparable concerns about mistakes, but criterion indicators suggested those were
more problematic for maladaptive perfectionists. Results supported the value of
incorporating adaptive and maladaptive criterion indicators in classification
models.
PMID- 25111706
TI - Compromises in career-related decisions: examining the role of compromise
severity.
AB - This study tested L. S. Gottfredson's (1996) revised compromise theory by
examining whether the relative importance of job sex type, job prestige, and
person-job interest congruence for predicting job choice changed as the level of
compromise required changed. The fully within-persons design had participants
engage in a simulated occupational choice task where job sex type and job
prestige were manipulated to be experimentally independent. Participants 1st
categorized jobs as unacceptable, acceptable, or preferred. Then, within each
category, they made further pairwise choices among jobs in that category. In
Study 1, participants were 168 college seniors (124 women, 44 men) from a large
Midwestern university. In Study 2, participants were 262 (146 women, 116 men)
individuals residing in the United States and recruited via Amazon's Mechanical
Turk platform. Across both studies, job sex type predicted choice when large
compromises were required. Across both studies, job prestige did not predict
choice when moderate compromises were required. In Study 2 but not Study 1,
person-job interest congruence predicted choice when minimal compromises were
required.
PMID- 25111707
TI - Male Asian international students' perceived racial discrimination, masculine
identity, and subjective masculinity stress: a moderated mediation model.
AB - This study examined male Asian international college students' perceptions of
racial discrimination, subjective masculinity stress, centrality of masculine
identity, and psychological distress by testing a moderated mediation model.
Participants were 160 male Asian international college students from 2 large
public universities. Participants' perceived racial discrimination was positively
related to their subjective masculinity stress only at high (but not low) levels
of masculine identity centrality. Additionally, subjective masculinity stress was
positively related to psychological distress, although this association was
stronger among those who reported high levels of masculine identity centrality.
The authors also detected a moderated mediation effect in which subjective
masculinity stress mediated the relationship between perceived racial
discrimination and psychological distress only at high (but not low) levels of
masculine identity centrality. These findings contribute to the counseling
psychology literature by highlighting the connections between race- and gender
related stressors as well as the relevance of masculine identity to an
understanding of men's mental health.
PMID- 25111709
TI - Sortase-based bio-organic strategies for macromolecular synthesis.
AB - Protein ligation sorted: SrtA is one of the molecules nature uses to perform
chemoselective ligation on amazingly complex protein molecules. Sortase-mediated
ligation (SML) with chemoselective reactions will find a variety of applications
in chemistry, biology, and medicine in the near future.
PMID- 25111708
TI - Characterization of BPSS1521 (bprD), a regulator of Burkholderia pseudomallei
virulence gene expression in the mouse model.
AB - The Gram-negative saprophytic bacterium Burkholderia pseudomallei is the
causative agent of melioidosis, a severe infectious disease of both humans and
animals. Severity of the disease is thought to be dependent on both the health
status of the host, including diabetes mellitus and kidney disease, and bacterial
derived factors. To identify the bacterial factors important during an acute
infection, gene expression profiles in the spleen, lung, and liver of BALB/c (Th2
prototype) and C57BL/6 mice (Th1 prototype) were determined using DNA
microarrays. This analysis identified BPSS1521 (bprD), a predicted
transcriptional regulator located in the type III secretion system (T3SS-3)
operon, to be up regulated, specifically in C57BL/6 mice. BALB/c mice infected
with a bprD mutant showed a shorter time to death and increased inflammation, as
determined by histopathological analysis and enumeration of bacteria in the
spleen. Elevated numbers of multinucleated giant cells (MNGCs), which is the
hallmark of melioidosis, were detected in both the wild-type and the bprD
mutants; a similar elevation occurs in melioidosis patients. One striking
observation was the increased expression of BPSS1520 (bprC), located downstream
of bprD, in the bprD mutant. BprC is a regulator of T6SS-1 that is required for
the virulence of B. pseudomallei in murine infection models. Deletion of bprD led
to the overexpression of bprC and a decreased time to death. bprD expression was
elevated in C57BL/6--as compared to BALB/c--mice, suggesting a role for BprD in
the natural resistance of C57BL/6 mice to B. pseudomallei. Ultimately, this
analysis using mice with different immune backgrounds may enhance our
understanding of the outcomes of infection in a variety of models.
PMID- 25111711
TI - Fluoroscopic removal of 'lost thread' IUCD's: a novel second line technique.
AB - Intrauterine contraceptive devices (IUCDs) with lost threads are an infrequent
but growing problem, and there are several successful first-line methods of
retrieving the devices. In the event of retrieval failure, we propose a novel
second-line technique using an endovascular snare under direct fluoroscopic
guidance. A total of 137 women were referred with 'lost string' IUCDs and
underwent removal using a snare device, designed for endovascular foreign body
retrieval, inserted transcervically. The snare is manipulated to catch the stem
of the IUCD under C-arm fluoroscopy. The successful removal rate was 89.6%. The
average screening time was 3 min 29 s, with a median air kerma of 12.33 mGy and
DAP of 985 mGy cm(2), which was considered minimal and comparable with similar
gynaecological interventional procedures. There were no significant
complications, with the procedure being tolerated and pain free in 97.8% of
cases.
PMID- 25111710
TI - Different requirements for GFRalpha2-signaling in three populations of cutaneous
sensory neurons.
AB - Many primary sensory neurons in mouse dorsal root ganglia (DRG) express one or
several GFRalpha's, the ligand-binding receptors of the GDNF family, and their
common signaling receptor Ret. GFRalpha2, the principal receptor for neurturin,
is expressed in most of the small nonpeptidergic DRG neurons, but also in some
large DRG neurons that start to express Ret earlier. Previously, GFRalpha2 has
been shown to be crucial for the soma size of small nonpeptidergic nociceptors
and for their target innervation of glabrous epidermis. However, little is known
about this receptor in other Ret-expressing DRG neuron populations. Here we have
investigated two populations of Ret-positive low-threshold mechanoreceptors that
innervate different types of hair follicles on mouse back skin: the small C-LTMRs
and the large Abeta-LTMRs. Using GFRalpha2-KO mice and immunohistochemistry we
found that, similar to the nonpeptidergic nociceptors, GFRalpha2 controls the
cell size but not the survival of both C-LTMRs and Abeta-LTMRs. In contrast to
the nonpeptidergic neurons, GFRalpha2 is not required for the target innervation
of C-LTMRs and Abeta-LTMRs in the back skin. These results suggest that different
factors drive target innervation in these three populations of neurons. In
addition, the observation that the large Ret-positive DRG neurons lack GFRalpha2
immunoreactivity in mature animals suggests that these neurons switch their
GFRalpha signaling pathways during postnatal development.
PMID- 25111712
TI - Bandgap engineering through nanocrystalline magnetic alloy grafting on reduced
graphene oxide.
AB - High conductivity and the absence of ferromagnetism in pristine graphene fail to
satisfy primary criteria for possible technological application in spintronics.
Opening of the bandgap in graphene is primarily desirable for such applications.
We report a simplified and novel approach of controlled grafting of a magnetic
alloy on reduced graphene oxide. This eventually leads to ferromagnetism of the
stable hybrid material at room temperature, with a large moment (~1.2 MUB) and a
remarkable decrease in conductivity (~10 times) compared to highly ordered
pyrolytic graphite. Our model band-structure calculation indicates that the
combined effect of controlled vacancies and impurities attributed to the
nanocrystalline alloy grafting leads to a promising step toward band gap
engineering.
PMID- 25111714
TI - No gain, no pain: NaV1.7 as an analgesic target.
AB - Chronic pain is one of the most complex and difficult to manage clinical
problems, with the therapeutic utility of current-generation analgesics
restricted by problems such as dose-limiting side effects, tolerance, and the
potential for addiction. The voltage-gated sodium channel NaV1.7 plays a key role
in setting the threshold for action potential generation in primary sensory
neurons, and humans that lack this channel are completely insensitive to pain. In
this Viewpoint, we examine the potential of NaV1.7 as an analgesic target a well
as the challenges involved in developing therapeutically useful subtype-selective
inhibitors of this ion channel.
PMID- 25111713
TI - Association between noninvasive fibrosis markers and cardio-vascular organ damage
among adults with hepatic steatosis.
AB - Evidence suggests that advanced fibrosis, as determined by the noninvasive NAFLD
fibrosis score (NFS), is a predictor of cardiovascular mortality in individuals
with ultrasonography-diagnosed NAFLD. Whether the severity of histology (i.e.,
fibrosis stage) is associated with more pronounced cardiovascular organ damage is
unsettled. In this study, we analyzed the clinical utility of NFS in assessing
increased carotid intima-media thickness (cIMT), and left ventricular mass index
(LVMI). In this cross-sectional study NFS, cIMT and LVMI were assessed in 400
individuals with ultrasonography-diagnosed steatosis. As compared with
individuals at low probability of liver fibrosis, individuals both at high and at
intermediate probability of fibrosis showed an unfavorable cardio-metabolic risk
profile having significantly higher values of waist circumference, insulin
resistance, high sensitivity C-reactive protein (hsCRP), fibrinogen, cIMT, and
LVMI, and lower insulin-like growth factor-1 (IGF-1) levels. The differences in
cIMT and LVMI remained significant after adjustment for smoking and metabolic
syndrome. In a logistic regression model adjusted for age, gender, smoking, and
diagnosis of metabolic syndrome, individuals at high probability of fibrosis had
a 3.9-fold increased risk of vascular atherosclerosis, defined as cIMT>0.9 mm,
(OR 3.95, 95% CI 1.12-13.87) as compared with individuals at low probability of
fibrosis. Individuals at high probability of fibrosis had a 3.5-fold increased
risk of left ventricular hypertrophy (LVH) (OR 3.55, 95% CI 1.22-10.34) as
compared with individuals at low probability of fibrosis. In conclusion, advanced
fibrosis, determined by noninvasive fibrosis markers, is associated with
cardiovascular organ damage independent of other known factors.
PMID- 25111715
TI - Fetal phenotype associated with the 22q11 deletion.
AB - The 22q11 deletion syndrome is one of the most common human microdeletion
syndromes, with a wide spectrum of abnormalities. The fetal phenotype associated
with the 22q11 deletion is poorly described in the literature. A national
retrospective study was performed from 74 feto-pathological examinations. The
objectives were to evaluate the circumstances of the 22q11 deletion diagnosis and
to describe fetal anomalies. Post mortem examinations were performed after 66
terminations of pregnancy and eight fetal deaths. The series included nine
fetuses from the first trimester, 55 from the second trimester, and ten from the
third trimester. A 22q11 FISH analysis was recommended for 57 fetuses after
multidisciplinary prenatal diagnostic counseling and for 17 fetuses by a fetal
pathologist. Conotruncal heart defects were the most common anomalies (65
fetuses), followed by thymus defects (62 fetuses), and malformations of the
urinary tract (25 fetuses). This study identified several unusual and severe
features rarely described in the literature. Neurological abnormalities were
described in ten fetuses, with seven neural tube defects and five
arhinencephalies. This series also included lethal malformations: two hypoplastic
left heart syndromes, two bilateral renal agenesis, and one tracheal agenesis.
Genetic analysis for a 22q11 deletion is usually indicated when a congenital
conotruncal heart and/or thymus defect is detected, but might also be useful in
case of other lethal or severe malformations that initially led to the
termination of pregnancy.
PMID- 25111718
TI - [Invitation to the Congress of Visceral Medicine 2014 in Leipzig].
PMID- 25111717
TI - [Prof. Dr. med. Peter Galle].
PMID- 25111716
TI - The ecology of prescription opioid abuse in the USA: geographic variation in
patients' use of multiple prescribers ("doctor shopping").
AB - PURPOSE: This study estimates the prevalence in US counties of opioid patients
who use large numbers of prescribers, the amounts of opioids they obtain, and the
extent to which their prevalence is predicted by ecological attributes of
counties, including general medical exposure to opioids. METHODS: Finite mixture
models were used to estimate the size of an outlier subpopulation of patients
with suspiciously large numbers of prescribers (probable doctor shoppers), using
a sample of 146 million opioid prescriptions dispensed during 2008. Ordinary
least squares regression models of county-level shopper rates included
independent variables measuring ecological attributes of counties, including
rates of patients prescribed opioids, socioeconomic characteristics of the
resident population, supply of physicians, and measures of healthcare service
utilization. RESULTS: The prevalence of shoppers varied widely by county, with
rates ranging between 0.6 and 2.5 per 1000 residents. Shopper prevalence was
strongly correlated with opioid prescribing for the general population,
accounting for 30% of observed county variation in shopper prevalence, after
adjusting for physician supply, emergency department visits, in-patient hospital
days, poverty rates, percent of county residents living in urban areas, and
racial/ethnic composition of resident populations. Approximately 30% of shoppers
obtained prescriptions in multiple states. CONCLUSIONS: The correlation between
prevalence of doctor shoppers and opioid patients in a county could indicate
either that easy access to legitimate medical treatment raises the risk of abuse
or that drug abusers take advantage of greater opportunities in places where
access is easy. Approaches to preventing excessive use of different prescribers
are discussed.
PMID- 25111719
TI - Endoscopic management for patients with serrated polyposis syndrome is feasible
and effective: a prospective observational study at a tertiary centre.
AB - BACKGROUND AND STUDY AIMS: Serrated polyposis syndrome is a rare condition in
which multiple serrated lesions develop all over the colon, which is thought to
be associated with an increased risk for the development of cancer. The aim of
this study was to investigate the feasibility of endoscopic treatment and
standardised surveillance in patients with this increasingly recognised syndrome.
METHODS: From September 2010 to November 2013, consecutive patients were included
in a prospective study. All patients underwent chromoendoscopy at first
presentation and during surveillance. Follow-up examinations were carried out at
3 month intervals until complete clearance was achieved. Afterwards, patients
entered a standardised surveillance protocol with a chromoendoscopic colonoscopy
annually. RESULTS: Altogether 100 colonoscopies were carried out in 28 patients,
with endoscopic resection of 436 lesions. Total clearance was accomplished in 27
patients (96.0 %) after 2.5 colonoscopies (range 1 - 8). Histology revealed 359
hyperplastic polyps (82.3 %), 37 sessile serrated adenomas (8.5 %), 36 low-grade
adenomas (8.3 %), and one patient with advanced colorectal cancer. Twelve
patients (42.8 %) had serrated polyps > 10 mm in size. During the surveillance
period, 86 additional lesions were detected and resected. The mean follow-up
period was 21.5 months (range 2 - 39 months). No interval carcinoma was detected
during the surveillance. CONCLUSIONS: The present study indicates that endoscopic
management in patients who meet the diagnostic criteria for serrated polyposis
syndrome is feasible and safe. In particular, the incidence of colorectal cancer
in this cohort was lower in comparison with previous studies.
PMID- 25111720
TI - [Actors in liver transplantation advocate greater transparency and systematic
evaluations of transplant centres].
AB - BACKGROUND: Following the introduction of the MELD score, the survival rates have
worsened after liver transplantation (LTX) in Germany. Existing organ shortages,
shorter survival rates after LTX, and failures in the liver allocation process
provide true challenges. Facilitated by a structured questionnaire, the
appropriate German liver transplantation actors were approached with regard to
these challenges for the first time. The aim was to provide a balanced experts'
view in an anonymous fashion thereby identifying areas for potential improvement.
METHOD: Data collection was performed by a structured, standardised, anonymous
survey of all LTX centres in Germany. RESULTS: We received 75 % replies of the
questionnaires, 35 of 36 participants responded to more than 75 % of all
questions. The following key points were highlighted. A minimum amount of LTX per
centre was deemed important and monetary incentives must not exist. The ultimate
goal of LTX is a prolongation of life and social as well as occupational
reintegration. Quality management and transparent LTX registers are prerequisites
for both adequate organ allocation and distribution of resources in order to
achieve the best possible transplant outcomes. CONCLUSION: The German liver
transplant experts consider transparency of organ allocation and systematic
evaluation of the quality of transplant centres and the transplantation process
itself to be mandatory, however, executed in a participatory way. A scoring
system to facilitate the decision making process in order to predict the
likelihood of satisfactory LTX outcome thereby circumventing some of the ethical
and constitutional doubts would be highly appreciated.
PMID- 25111721
TI - Invasive cardiac aspergillosis after orthotopic liver transplantation.
AB - Invasive aspergillus infection occurs in 5 - 42 % of liver-transplanted
recipients and is a dangerous complication, associated with high mortality if
untreated. However, the early diagnosis of invasive aspergillosis can be elusive,
as clinical signs are unspecific and the pathogenic agent is difficult to
demonstrate. We here report about a 58-year-old man with acute liver failure
caused by newly diagnosed chronic hepatitis B infection who underwent liver
transplantation. The postoperative course was uneventful, and the patient was
discharged after 30 days. After 105 days the patient was readmitted because of
fever, recurrent chest and abdominal pain. Computed tomography revealed a cardiac
lesion; other diagnostic steps including bone-marrow and endomycordial biopsy,
virological and microbiological investigations gave no clear findings. To exclude
a malignant process, thoracotomy with mass and simultaneous lower left lobe
resection were performed. Histopathological findings revealed an invasive
perimyocardial aspergillosis. Immediate intravenous therapy with voriconazole and
caspofungin was initiated and monitoring of the mass was performed with
transesophageal echocardiography and Cardio-MRI. Due to slightly increase of the
lesion, medication was switched to posaconazole and caspofungin. Under this dual
fungal treatment the lesion regressed and the patient could be discharged after
two months in good clinical condition. Frequent Cardio-MRI scan after discharge
showed further mass-regression. Therefore antifungal treatment was switched to
oral posaconazole mono-therapy. After one year, complete reduction of the mass
was achieved and antifungal therapy was discontinued. Recent diagnostic imaging
follow-up showed no pathological finding.
PMID- 25111722
TI - [Treatment of a subsequently detected, iatrogenic colonic perforation via minimal
invasive rendezvous procedure].
AB - Laparoscopic surgery as primary therapeutical option for iatrogenic colonic
perforation after colonoscopy can be complemented by intraoparative colonoscopy
in order to detect and treat even difficult accessible lesions. Via the presented
method minimal invasisve detection and therapy of perforation can be conducted
safely and can lead to reduction of morbidity.
PMID- 25111723
TI - [Incidence and treatment of chemotherapy-induced nausea and emesis in
gastrointestinal cancer].
AB - The incidence of gastrointestinal (GI) cancer is increasing, with approximately 2
million new cases diagnosed worldwide and about 1.2 million patients dying per
year. In Europe, about 500 ,000 people per year are newly diagnosed with GI
cancer. The most frequent cancer types that undergo chemotherapy include cancer
of the oesophagus, stomach, pancreas, biliary tract and colorectum. In the last
years, various new agents and combinations have been demonstrated to improve the
prognosis of patients with GI cancer. However, with the introduction of new and
more effective systemic treatments, the need for supportive treatment has become
more complex. There has been significant improvement in the management of nausea
and vomiting arising from highly and moderately emetogenic chemotherapy.
Nevertheless, vomiting and especially nausea continue to be two of the most
distressing side effects of antineoplastic treatment. For the prevention of
chemotherapy-induced nausea and vomiting in highly emetogenic therapy, a triple
therapy including a 5-HT3-receptor antagonist (RA), dexamethasone and an NK1-RA,
aprepitant or fosaprepitant are recommended. In moderately emetogenic regimens,
updated guidelines recommend the combination of the second-generation 5-HT3-RA
palonosetron with dexamethasone, providing improved protection against acute
nausea and vomiting, and demonstrating superior prevention in the delayed phase.
This review provides an update of the revised clinical guidelines for antiemetic
treatment and prophylaxis in GI cancer patients receiving chemotherapy.
PMID- 25111724
TI - [Differential diagnosis of diarrhoea].
AB - Diarrhoea is a common symptom and numerous differential diagnoses must be
considered. This article illustrates approaches for a rational and efficient work
up based on practical facilities in acute diarrhoea and fostered by 4 key
questions scrutinising chronic diarrhoea. The applications of imaging methods
(endoscopy, ultrasonography) are discussed along with infectious topics and
function testing. The aim of this contribution is to help patients to get a
precise diagnosis in a most rational way. This implies a transparent and targeted
medical strategy, avoiding selective intuitions ("trial and error") as well as
extensive diagnostic overdoing in the case of only putative diarrhoea. Knowing
the potential of diagnostic methods which are (or can) possibly not performed
regularly in the physician's office, and their requirements/limitations is an
important component in this situation. The basic fundament for application of
such methods, however, and the clue to economic diagnosis as well as the
differential diagnosis of diarrhoeal diseases are the history and simple tests.
PMID- 25111725
TI - [Endoscopic or surgical cystogastrostomy for pancreatic pseudocysts: finally a
clear answer to an old question?].
PMID- 25111726
TI - Twinship as a resource: zygosity- and gender-based comparison of twins' attitudes
toward twinship.
AB - Aiming to perform the first sociological survey of Hungarian twins, our main
question was whether being a twin has positive consequences on one's life. Adult
twins completed our questionnaire at three Hungarian summer twin festivals, in
hospitals during medical twin studies, and on some websites online. Data
represent 140 twin pairs (mean age: 38.2 +/- 14.6 years). We employed some
indices for measuring the resource nature of twinship. Three main types of
benefits were distinguished: profit of attraction, as 'material capital'; the
easier obtainability of cultural goods when twins take part in it, as 'cultural
capital'; and positive aspects of an a priori existing dyadic relation, as
'relational capital'. We were interested in the difference among types of twins
regarding advantages. We paid special attention to the five groups of twins
derived from gender and zygosity (i.e., monozygotic females, monozygotic males,
dizygotic females, dizygotic males, opposite-sex pairs). Our analysis showed that
Hungarian twins involved in our research basically enjoy their twinship; during
their lives they used and still make use of different benefits given by it. In
our twin samples, women had more advantages from being a twin than men.
Significant differences could be observed on all indicators between monozygotic
and dizygotic twins.
PMID- 25111729
TI - SurfKin: an ab initio kinetic code for modeling surface reactions.
AB - In this article, we describe a C/C++ program called SurfKin (Surface Kinetics) to
construct microkinetic mechanisms for modeling gas-surface reactions.
Thermodynamic properties of reaction species are estimated based on density
functional theory calculations and statistical mechanics. Rate constants for
elementary steps (including adsorption, desorption, and chemical reactions on
surfaces) are calculated using the classical collision theory and transition
state theory. Methane decomposition and water-gas shift reaction on Ni(111)
surface were chosen as test cases to validate the code implementations. The good
agreement with literature data suggests this is a powerful tool to facilitate the
analysis of complex reactions on surfaces, and thus it helps to effectively
construct detailed microkinetic mechanisms for such surface reactions. SurfKin
also opens a possibility for designing nanoscale model catalysts.
PMID- 25111727
TI - Complications associated with the pedicled nasoseptal flap for skull base
reconstruction.
AB - OBJECTIVES/HYPOTHESIS: To analyze complications associated with nasoseptal flap
elevation and reconstruction in endoscopic skull base surgery. STUDY DESIGN: Case
series. METHODS: Retrospective chart review of all patients who underwent
nasoseptal flap procedure in our institution between 2008 and 2013. RESULTS: A
total of 121 patients were identified with a mean follow-up time of 10.4 months.
Complications associated with this procedure occurred in 33 patients (27%). The
majority of complications were related to the septal donor site and included
septal perforation, cartilage necrosis, and prolonged crusting. Other
complications included intraoperative injury to the flap pedicle (n = 4) or
recurrent/persistent cerebrospinal fluid leak occurring in the early
postoperative period (n = 7). Long-term quality-of-life data assessed via
Sinonasal Outcome Test-22 questionnaires did not reveal notable differences when
compared to preoperative scores. CONCLUSION: The complication rate associated
with nasoseptal flap elevation and inset is higher than previously described. The
majority of complications became manifest beyond the immediate postoperative
period and were associated with the septal donor site, including septal
perforation, prolonged crusting, and cartilage necrosis. We hypothesize that
donor site morbidity may be related to compromise of the contralateral septal
vascular supply during the procedure. The range and frequency of complications of
nasal septal flap surgery should be considered in counseling patients who may
receive a nasoseptal flap for skull base reconstruction.
PMID- 25111731
TI - Measurement of T1 relaxation time of osteochondral specimens using VFA-SWIFT.
AB - PURPOSE: To evaluate the feasibility of SWIFT with variable flip angle (VFA) for
measurement of T1 relaxation time in Gd-agarose-phantoms and osteochondral
specimens, including regions of very short T2 *, and compare with T1 measured
using standard methods METHODS: T1 s of agarose phantoms with variable
concentration of Gd-DTPA2- and nine pairs of native and trypsin-treated bovine
cartilage-bone specimens were measured. For specimens, VFA-SWIFT, inversion
recovery (IR) fast spin echo (FSE) and saturation recovery FSE were used. For
phantoms, additionally spectroscopic IR was used. Differences and agreement
between the methods were assessed using nonparametric Wilcoxon and Kruskal-Wallis
tests and intraclass correlation. RESULTS: The different T1 mapping methods
agreed well in the phantoms. VFA-SWIFT allowed reliable measurement of T1 in the
osteochondral specimens, including regions where FSE-based methods failed. The T1
s measured by VFA-SWIFT were shifted toward shorter values in specimens. However,
the measurements correlated significantly (highest correlation VFA-SWIFT versus
FSE was r = 0.966). SNR efficiency was generally highest for SWIFT, especially in
the subchondral bone. CONCLUSION: Feasibility of measuring T1 relaxation time
using VFA-SWIFT in osteochondral specimens and phantoms was demonstrated. A shift
toward shorter T1 s was observed for VFA-SWIFT in specimens, reflecting the
higher sensitivity of SWIFT to short T2 * spins. Magn Reson Med 74:175-184, 2015.
(c) 2014 Wiley Periodicals, Inc.
PMID- 25111732
TI - Tracking the actions and possessions of agents.
AB - We propose that there is a powerful human disposition to track the actions and
possessions of agents. In two experiments, 3-year-olds and adults viewed sets of
objects, learned a new fact about one of the objects in each set (either that it
belonged to the participant, or that it possessed a particular label), and were
queried about either the taught fact or an unrelated dimension (preference)
immediately after a spatiotemporal transformation, and after a delay. Adults
uniformly tracked object identity under all conditions, whereas children tracked
identity more when taught ownership versus labeling information, and only
regarding the taught fact (not the unrelated dimension). These findings suggest
that the special attention that children and adults pay to agents readily extends
to include inanimate objects. That young children track an object's history,
despite their reliance on surface features on many cognitive tasks, suggests that
unobservable historical features are foundational in human cognition.
PMID- 25111733
TI - Development of an applicator for eye lens dosimetry during radiotherapy.
AB - OBJECTIVE: To develop an applicator for in vivo measurements of lens dose during
radiotherapy. METHODS: A contact lens-shaped applicator made of acrylic was
developed for in vivo measurements of lens dose. This lens applicator allows the
insertion of commercially available metal oxide semiconductor field effect
transistors (MOSFETs) dosemeters. CT images of an anthropomorphic phantom with
and without the applicator were acquired. Ten volumetric modulated arc therapy
plans each for the brain and the head and neck cancer were generated and
delivered to an anthropomorphic phantom. The differences between the measured and
the calculated doses at the lens applicator, as well as the differences between
the measured and the calculated doses at the surface of the eyelid were acquired.
RESULTS: The average difference between the measured and the calculated doses
with the applicator was 3.1 +/- 1.8 cGy with a micro MOSFET and 2.8 +/- 1.3 cGy
with a standard MOSFET. The average difference without the lens applicator was
4.8 +/- 5.2 cGy with the micro MOSFET and 5.7 +/- 6.5 cGy with the standard
MOSFET. The maximum difference with the micro MOSFET was 10.5 cGy with the
applicator and 21.1 cGy without the applicator. For the standard MOSFET, it was
6.8 cGy with the applicator and 27.6 cGy without the applicator. CONCLUSION: The
lens applicator allowed reduction of the differences between the calculated and
the measured doses during in vivo measurement for the lens compared with in vivo
measurement at the surface of the eyelid. ADVANCES IN KNOWLEDGE: By using an
applicator for in vivo dosimetry of the eye lens, it was possible to reduce the
measurement uncertainty.
PMID- 25111734
TI - AGR2, an endoplasmic reticulum protein, is secreted into the gastrointestinal
mucus.
AB - The MUC2 mucin is the major constituent of the two mucus layers in colon. Mice
lacking the disulfide isomerase-like protein Agr2 have been shown to be more
susceptible to colon inflammation. The Agr2(-/-) mice have less filled goblet
cells and were now shown to have a poorly developed inner colon mucus layer. We
could not show AGR2 covalently bound to recombinant MUC2 N- and C-termini as have
previously been suggested. We found relatively high concentrations of Agr2 in
secreted mucus throughout the murine gastrointestinal tract, suggesting that Agr2
may play extracellular roles. In tissue culture (CHO-K1) cells, AGR2 is normally
not secreted. Replacement of the single Cys in AGR2 with Ser (C81S) allowed
secretion, suggesting that modification of this Cys might provide a mechanism for
circumventing the KTEL endoplasmic reticulum retention signal. In conclusion,
these results suggest that AGR2 has both intracellular and extracellular effects
in the intestine.
PMID- 25111735
TI - Generation of rat-induced pluripotent stem cells from a new model of metabolic
syndrome.
AB - We recently characterized DahlS.Z-Leprfa/Leprfa (DS/obese) rats, derived from a
cross between Dahl salt-sensitive rats and Zucker rats, as a new animal model of
metabolic syndrome (MetS). Although the phenotype of DS/obese rats is similar to
that of humans with MetS, the pathophysiological and metabolic characteristics in
each cell type remain to be clarified. Hence, the establishment of induced
pluripotent stem cells (iPSCs) derived from MetS rats is essential for
investigations of MetS in vitro. Reports of rat iPSCs (riPSCs), however, are few
because of the difficulty of comparing to other rodents such as mouse. Recently,
the advantage of using mesenchymal stromal cells (MSCs) as a cell source for
generating iPSCs was described. We aimed to establish riPSCs from MSCs in adipose
tissues of both DS/obese rats and their lean littermates, DahlS.Z-Lepr+/Lepr+
(DS/lean) rats using lentivirus vectors with only three factors Oct4, Klf4, and
Sox2 without c-Myc. The morphology, gene expression profiles, and protein
expression of established colonies showed embryonic stem cell (ESCs)-like
properties, and the differentiation potential into cells from all three germ
layers both in vitro and in vivo (teratomas). Both riPSCs became adipocytes after
induction of adipogenesis by insulin, T3, and dexamethasone. Real-time PCR
analysis also revealed that both riPSCs and the adipose tissue from DS/obese and
DS/lean rats possess similar expression patterns of adipocyte differentiation
related genes. We succeeded in generating riPSCs effectively from MSCs of both
DS/obese and DS/lean rats. These riPSCs may well serve as highly effective tools
for the investigation of MetS pathophysiology in vitro.
PMID- 25111736
TI - Retreatment of men with metastatic castrate-resistant prostate cancer with
abiraterone.
AB - BACKGROUND: Abiraterone acetate (AA), oral CYP17 inhibitor, is an active agent in
the treatment of metastatic castrate-resistant prostate cancer (mCRPC). METHODS:
We (R.L.A and N.A) retrospectively evaluated outcome in 12 men who were re
treated with AA following prior treatment with AA at the Princess Margaret Cancer
Centre. RESULTS: All men were heavily pre-treated for mCRPC with a median of four
prior lines of therapy, one of which was AA (given either pre- or post
chemotherapy). Eleven out of 12 (92%) men stopped their first treatment course of
AA due to progression and one stopped for financial reasons. Seven men had a PSA
decrease >=50% following their first AA treatment, of which three (46%) had a PSA
decrease >=50% to AA re-treatment. The responses to AA re-treatment were
generally short-lived with a median biochemical progression-free survival of 2.3
months and median treatment duration of 3.2 months. No PSA responses to AA re
treatment were seen in five men who did not have an initial PSA response to AA.
CONCLUSIONS: Our data suggest that AA re-challenge may have limited benefit in
select men with mCRPC, and warrants further formal research.
PMID- 25111737
TI - Phosphorus reclamation through hydrothermal carbonization of animal manures.
AB - Projected shortages of global phosphate have prompted investigation of methods
that could be employed to capture and recycle phosphate, rather than continue to
allow the resource to be essentially irreversibly lost through dilution in
surface waters. Hydrothermal carbonization of animal manures from large farms was
investigated as a scenario for the reclamation of phosphate for agricultural use
and mitigation of the negative environmental impact of phosphate pollution.
Hydrothermal reaction conditions were identified for poultry, swine, and cattle
manures that resulted in hydrochar yields of 50-60% for all three manures, and
>90% of the total phosphorus present in these systems was contained in the
hydrochars as precipitated phosphate salts. Phosphate recovery was achieved in
yields of 80-90% by subsequent acid treatment of the hydrochars, addition of base
to acid extracts to achieve a pH of 9, and filtration of principally calcium
phosphate. Phosphate recovery was achieved in yields of 81-87% based on starting
manures by subsequent acid treatment of the hydrochars, addition of base to acid
extracts to achieve a pH of 9, and filtration of principally calcium phosphate.
Swine and cattle manures produced hydrochars with combustion energy contents
comparable to those of high-end sub-bituminous coals.
PMID- 25111738
TI - Phosphatidic acid in neuronal development: a node for membrane and cytoskeleton
rearrangements.
AB - Phosphatidic acid (PA) is the simplest phospholipid naturally existing in all
living organisms. It constitutes only a minor fraction of the total cell lipids
but has attracted considerable attention being both a lipid second messenger and
a modulator of membrane shape. The pleiotropic functions of PA are the direct
consequence of its very simple chemical structure consisting of only two acyl
chains linked by ester bonds to two adjacent hydroxyl groups of glycerol, whose
remaining hydroxyl group is esterified with a phosphomonoester group. Hence the
small phosphate head group of PA gives it the shape of a cone providing
flexibility and negative curvatures in the context of a lipid bilayer. In
addition, the negatively charged phosphomonoester headgroup of PA is unique
because it can potentially carry one or two negative charges playing a role in
the recruitment of positively charged molecules to biomembranes. In consequence,
PA has been proposed to play various key cellular functions. In the brain, a fine
balance between cell growth, migration and differentiation, and cell death is
required to sculpt the nervous system during development. In this review, we will
summarize the various functions that have been proposed for PA in neuronal
development.
PMID- 25111739
TI - The role of functional form in causal-based categorization.
AB - Two experiments tested how the functional form of the causal relations that link
features of categories affects category-based inferences. Whereas independent
causes can each bring about an effect by themselves, conjunctive causes all need
to be present for an effect to occur. The causal model view of category
representations is extended to include a representation of conjunctive causes and
then predictions are derived for 3 category-based judgments: classification,
conditional feature predictions, and feature likelihoods. Experiment 1 revealed
that subjects' judgments on all 3 tasks were not only sensitive to whether causes
were independent or conjunctive but also conformed to the causal model
predictions, albeit with an important exception. Experiment 2 revealed that
inferences with independent and conjunctive causes were affected quite
differently by a manipulation of the strengths of the causal relations (and in
the manner predicted by the model). This is the 1st study to show how a single
representation of a category's causal knowledge can account for 3 category-based
judgments with the same model parameters. Other models of causal-based categories
are unable to account for the observed effects.
PMID- 25111740
TI - Spotted fever from Rickettsia typhi in an older woman: a case report from a
geographic area where it would not be expected.
AB - We describe the case of a 75-year-old woman presenting with spotted fever
followed by acute renal failure and septic shock. The infection was caused by
Rickettsia typhi, not reported in Calabria district (southern Italy) since World
War II. The diagnosis of murine typhus was made 3 days after admission and was
based solely on clinical criteria when her worsening condition required a prompt
move to the intensive care unit. Therapy with tigecycline was then started
immediately and the patient improved dramatically. The diagnosis of murine typhus
was confirmed 10 days after admission by immunofluorescence assay. Our case is an
example of how the diagnosis of murine typhus is challenging. However, in the
case of a disease lacking specific symptoms, clinicians should never forget that,
even in geographic areas considered free of flea-borne diseases, the components
of the enzootic cycle are present and the diagnosis should never be
underestimated.
PMID- 25111742
TI - Unique mechanism of facile polymorphic conversion of acetaminophen in aqueous
medium.
AB - Rapid polymorphic conversion of acetaminophen (APAP) in solution, from metastable
orthorhombic Form II to the stable monoclinic Form I, is well-known. The
mechanism is believed to be solution-mediated phase transformation (SMPT), but
with little experimental evidence. The present study was undertaken to understand
this phenomenon from both thermodynamic and kinetic perspectives. Reliable
apparent solubility of Form II was measured, for the first time, in 0.15 M
aqueous NaCl solution at 37 degrees C. The solubility ratio of Form II over Form
I, 1.27 +/- 0.04, is quite low, which translates to a relatively low
thermodynamic driving force for the conversion. Further solution crystallization
experiments at supersaturation levels equal to or much greater than Form II
solubility did not result in any crystallization in 10 days. Therefore, fast
conversion is not possible through SMPT. To explore alternative mechanisms,
molecular dynamics (MD) simulations were conducted to investigate the molecular
level dissolution behavior and the solid state differences between the two
polymorphs. The MD simulations reveal very different behavior. Form II exhibits a
much higher rate of H-bond breakage, leading to the accumulation of a large
number of disordered APAP molecules on the crystal surface. This thick disordered
molecular layer provides a high local acetaminophen concentration which could be
responsible for the fast crystallization of Form I. This was further supported by
the observations made, using polarized light microscopy and powder X-ray
diffractometry, when monitoring Form II crystals coming into contact with NaCl
solution. We thus concluded that the hydrated surface layer is the "catalyst" for
the facile phase conversion. This new mechanism, termed as SurFPT (surface
facilitated phase transformation), is much more effective in promoting
polymorphic transformation than the well-known SMPT.
PMID- 25111741
TI - Association between early temperament and depression at 18 years.
AB - BACKGROUND: Early childhood temperament, particularly negative emotionality (high
tendency to show distress), may be a risk factor for subsequent depression.
METHODS: Using data from a large UK cohort (Avon Longitudinal Study of Parents
and Children), we examined the association between temperament on the
Emotionality Activity Sociability Questionnaire at age 6 and ICD-10 depression at
18. Results were adjusted for a range of confounders. RESULTS: Children with high
emotionality scores at age 6 had a 20% (7-36%) increase in the odds of being
diagnosed with depression at age 18. CONCLUSIONS: Depression at 18 years has an
early developmental diathesis, which means we may be able to identify children at
risk of developing depression in young adulthood.
PMID- 25111743
TI - Iron concentration increases after moderate endurance exercise: implications for
screening of blood transfusion in sports.
PMID- 25111744
TI - Assessment of the neurotoxic potential of exposure to 50Hz extremely low
frequency electromagnetic fields (ELF-EMF) in naive and chemically stressed PC12
cells.
AB - Increasing exposure to extremely low frequency electromagnetic fields (ELF-EMF),
generated by power lines and electric appliances, raises concern about potential
adverse health effects of ELF-EMF. The central nervous system is expected to be
particularly vulnerable to ELF-EMF as its function strongly depends on electrical
excitability. We therefore investigated effects of acute (30min) and sub-chronic
(48h) exposure to 50Hz ELF-EMF on naive and chemically stressed pheochromocytoma
(PC12) cells. The latter have higher levels of iron and/or reactive oxygen
species (ROS) and display increased vulnerability to environmental insults.
Effects of ELF-EMF on Ca(2+)-homeostasis, ROS production and membrane integrity
were assessed using Fura-2 single cell fluorescence microscopy, H2-DCFDA and CFDA
assays, respectively. Our data demonstrate that acute exposure of naive PC12
cells to 50Hz ELF-EMF up to 1000MUT fails to affect basal or depolarization
evoked [Ca(2+)]i. Moreover, sub-chronic ELF-EMF exposure up to 1000MUT has no
consistent effects on Ca(2+)-homeostasis in naive PC12 cells and does not affect
ROS production and membrane integrity. Notably, in chemically stressed PC12 cells
both acute and sub-chronic ELF-EMF exposure also failed to exert consistent
effects on Ca(2+)-homeostasis, ROS production and membrane integrity. Our
combined findings thus indicate that exposure to 50Hz ELF-EMF up to 1000MUT, i.e.
10,000 times above background exposure, does not induce neurotoxic effects in
vitro, neither in naive nor in chemically stressed PC12 cells. Though our data
require confirmation, e.g. in developing neuronal cells in vitro or (developing)
animals, it appears that the neurotoxic risk of ELF-EMF exposure is limited.
PMID- 25111745
TI - Treatment of latent tuberculosis infection: a network meta-analysis.
AB - BACKGROUND: Effective treatment of latent tuberculosis infection (LTBI) is an
important component of TB elimination programs. Promising new regimens that may
be more effective are being introduced. Because few regimens can be directly
compared, network meta-analyses, which allow indirect comparisons to be made,
strengthen conclusions. PURPOSE: To determine the most efficacious regimen for
preventing active TB with the lowest likelihood of adverse events to inform LTBI
treatment policies. DATA SOURCES: PubMed, EMBASE, and Web of Science up to 29
January 2014; clinical trial registries; and conference abstracts. STUDY
SELECTION: Randomized, controlled trials that evaluated LTBI treatment in humans
and recorded at least 1 of 2 prespecified end points (preventing active TB or
hepatotoxicity), without language or date restrictions. DATA EXTRACTION: Data
from eligible studies were independently extracted by 2 investigators according
to a standard protocol. DATA SYNTHESIS: Of the 1516 articles identified, 53
studies met the inclusion criteria. Data on 15 regimens were available; of 105
possible comparisons, 42 (40%) were compared directly. Compared with placebo,
isoniazid for 6 months (odds ratio [OR], 0.64 [95% credible interval {CrI}, 0.48
to 0.83]) or 12 months or longer (OR, 0.52 [CrI, 0.41 to 0.66]), rifampicin for 3
to 4 months (OR, 0.41 [CrI, 0.18 to 0.86]), and rifampicin-isoniazid regimens for
3 to 4 months (OR, 0.52 [CrI, 0.34 to 0.79]) were efficacious within the network.
LIMITATIONS: The risk of bias was unclear for many studies across various
domains. Evidence was sparse for some comparisons, particularly hepatotoxicity.
CONCLUSION: Comparison of different LTBI treatment regimens showed that various
therapies containing rifamycins for 3 months or more were efficacious at
preventing active TB, potentially more so than isoniazid alone. Regimens
containing rifamycins may be effective alternatives to isoniazid monotherapy.
PRIMARY FUNDING SOURCE: None.
PMID- 25111746
TI - Ene-hydrazide from enol triflate for the regioselective Fischer indole synthesis.
AB - Ene-hydrazide prepared from enol triflate undergoes a Fischer indolization
reaction to give the corresponding indole with complete regioselectivity. The
starting enol triflate is readily accessed in regiochemically defined form from
the ketone precursor via various well-established methods. This new protocol was
successfully applied to the synthesis of desbromoarborescidine A, a natural beta
carboline alkaloid, difficult to prepare with conventional Fischer indole
synthesis.
PMID- 25111747
TI - Excess body weight affects HbA1c progression irrespective of baseline HbA1c
levels in Japanese individuals: a longitudinal retrospective study.
AB - PURPOSE/AIM: Obese individuals with normal HbA1c levels and low-body-weight
individuals with high-normal HbA1c levels are frequently encountered in clinical
settings, but the effects of these phenotypes on the onset of diabetes are poorly
understood. Therefore, we addressed this issue in a longitudinal study. MATERIALS
AND METHODS: We analyzed clinical parameters, including body mass index (BMI) and
HbA1c levels, in 5325 non-diabetic Japanese people aged 20-75 years who underwent
four medical checkups between 1999 (baseline) and 2007. The subjects were then
classified into six baseline BMI categories, each of which was divided into two
HbA1c groups, resulting in a total of 12 groups. RESULTS: In 405 obese subjects
with a normal baseline HbA1c (BMI >= 27.0 kg/m(2), HbA1c 5.2-5.6%), the mean
HbA1c level increased during the study period, and 50.9% developed
prediabetes/diabetes. In contrast, in 77 low-body-weight subjects with a high
normal baseline HbA1c (BMI <= 18.9 kg/m(2), HbA1c 5.7-6.4%), the mean HbA1c level
remained constant. Similar changes occurred in the other groups during the study,
resulting in a linear increase in HbA1c levels with increasing BMI. CONCLUSION:
Our results suggest that approximately half of the obese individuals with HbA1c
in the normal range develop prediabetes or diabetes within 8 years, whereas low
body-weight individuals with high-normal HbA1c are less likely to exhibit
worsening in glycemia. Thus, excess body weight may be the primary therapeutic
target to prevent the early onset of diabetes, regardless of the individual's
HbA1c.
PMID- 25111748
TI - Infrared spectroscopic studies on the V-ATPase.
AB - V-ATPase is an ATP-driven rotary motor that vectorially transports ions. Together
with F-ATPase, a homologous protein, several models on the ion transport have
been proposed, but their molecular mechanisms are yet unknown. V-ATPase from
Enterococcus hirae forms a large supramolecular protein complex (total molecular
weight: ~700,000) and physiologically transports Na+ and Li+ across a hydrophobic
lipid bilayer. Stabilization of these cations in the binding site has been
discussed on the basis of X-ray crystal structures of a membrane-embedded domain,
the K-ring (Na+ and Li+ bound forms). Sodium or lithium ion binding-induced
difference FTIR spectra of the intact E. hirae V-ATPase have been measured in
aqueous solution at physiological temperature. The results suggest that sodium or
lithium ion binding induces the deprotonation of Glu139, a hydrogen-bonding
change in the tyrosine residue and rigid alpha-helical structures. Identical
difference FTIR spectra between the entire V-ATPase complex and K-ring strongly
suggest that protein interaction with the I subunit does not cause large
structural changes in the K-ring. This result supports the previously proposed
Na+ transport mechanism by V-ATPase stating that a flip-flop movement of a
carboxylate group of Glu139 without large conformational changes in the K-ring
accelerates the replacement of a Na+ ion in the binding site. This article is
part of a Special Issue entitled: Vibrational spectroscopies and bioenergetic
systems.
PMID- 25111749
TI - Characterisation of the LH2 spectral variants produced by the photosynthetic
purple sulphur bacterium Allochromatium vinosum.
AB - This study systematically investigated the different types of LH2 produced by
Allochromatium (Alc.) vinosum, a photosynthetic purple sulphur bacterium, in
response to variations in growth conditions. Three different spectral forms of
LH2 were isolated and purified, the B800-820, B800-840 and B800-850 LH2 types,
all of which exhibit an unusual split 800 peak in their low temperature
absorption spectra. However, it is likely that more forms are also present.
Relatively more B800-820 and B800-840 are produced under low light conditions,
while relatively more B800-850 is produced under high light conditions.
Polypeptide compositions of the three different LH2 types were determined by a
combination of HPLC and TOF/MS. The B800-820, B800-840 and B800-850 LH2 types all
have a heterogeneous polypeptide composition, containing multiple types of both
alpha and beta polypeptides, and differ in their precise polypeptide composition.
They all have a mixed carotenoid composition, containing carotenoids of the
spirilloxanthin series. In all cases the most abundant carotenoid is rhodopin;
however, there is a shift towards carotenoids with a higher conjugation number in
LH2 complexes produced under low light conditions. CD spectroscopy, together with
the polypeptide analysis, demonstrates that these Alc. vinosum LH2 complexes are
more closely related to the LH2 complex from Phs. molischianum than they are to
the LH2 complexes from Rps. acidophila.
PMID- 25111750
TI - Connection between the membrane electron transport system and Hyn hydrogenase in
the purple sulfur bacterium, Thiocapsa roseopersicina BBS.
AB - Thiocapsa. roseopersicina BBS has four active [NiFe] hydrogenases, providing an
excellent opportunity to examine their metabolic linkages to the cellular redox
processes. Hyn is a periplasmic membrane-associated hydrogenase harboring two
additional electron transfer subunits: Isp1 is a transmembrane protein, while
Isp2 is located on the cytoplasmic side of the membrane. In this work, the
connection of HynSL to various electron transport pathways is studied. During
photoautotrophic growth, electrons, generated from the oxidation of thiosulfate
and sulfur, are donated to the photosynthetic electron transport chain via
cytochromes. Electrons formed from thiosulfate and sulfur oxidation might also be
also used for Hyn-dependent hydrogen evolution which was shown to be light and
proton motive force driven. Hyn-linked hydrogen uptake can be promoted by both
sulfur and nitrate. The electron flow from/to HynSL requires the presence of Isp2
in both directions. Hydrogenase-linked sulfur reduction could be inhibited by a
QB site competitive inhibitor, terbutryne, suggesting a redox coupling between
the Hyn hydrogenase and the photosynthetic electron transport chain. Based on
these findings, redox linkages of Hyn hydrogenase are modeled.
PMID- 25111751
TI - Vegetating nodules following erosions on the oral cavity: a quiz. Iatrogenic
Kaposi's sarcoma associated with pemphigus vulgaris.
PMID- 25111752
TI - Prussian blues as a cathode material for lithium ion batteries.
AB - Prussian blues (or iron cyanides) and their analogues are attractive in both
fundamental studies and industrial applications owing to their chemical and
structural diversity. The large open space in their framework provides tunnels
and space for the transport and storage of lithium ions. Two Prussian blues were
synthesized by a co-precipitation method. The nanosized Fe4 [Fe(CN)6 ]3 and cubic
FeFe(CN)6 deliver reversible capacities of 95 mAh g(-1) and 138 mAh g(-1) ,
respectively. In comparison, FeFe(CN)6 shows cycling and rate performances
superior to Fe4 [Fe(CN)6 ]3 .
PMID- 25111753
TI - Horizontal transmission of a parasite is influenced by infected host phenotype
and density.
AB - Transmission is a key determinant of parasite fitness, and understanding the
dynamics of transmission is fundamental to the ecology and evolution of host
parasite interactions. Successful transmission is often reliant on contact
between infected individuals and susceptible hosts. The social insects consist of
aggregated groups of genetically similar hosts, making them particularly
vulnerable to parasite transmission. Here we investigate how the ratio of
infected to susceptible individuals impacts parasite transmission, using the
honey bee, Apis mellifera and its microsporidian parasite Nosema ceranae. We used
2 types of infected hosts found simultaneously in colonies; sterile female
workers and sexual males. We found a higher ratio of infected to susceptible
individuals in groups resulted in a greater proportion of susceptibles becoming
infected, but this effect was non-linear and interestingly, the ratio also
affected the spore production of infected individuals. The transmission level was
much greater in an experiment where the infected individuals were drones than in
an experiment where they were workers, suggesting drones may act as intracolonial
'superspreaders'. Understanding the subtleties of transmission and how it is
influenced by the phenotype of the infected/susceptible individuals is important
for understanding pathogen transmission at population level, and for optimum
targeting of parasite control strategies.
PMID- 25111754
TI - One third of dynamic protein expression profiles can be predicted by a simple
rate equation.
AB - Cells respond to environmental stimuli with expression changes at both the mRNA
and protein level, and a plethora of known and unknown regulators affect
synthesis and degradation rates of the resulting proteins. To investigate the
major principles of gene expression regulation in dynamic systems, we estimated
protein synthesis and degradation rates from parallel time series data of mRNA
and protein expression and tested the degree to which expression changes can be
modeled by a simple linear differential equation. Examining three published
datasets for yeast responding to diamide, rapamycin, and sodium chloride
treatment, we find that almost one-third of genes can be well-modeled, and the
estimated rates assume realistic values. Prediction quality is linked to low
measurement noise and the shape of the expression profile. Synthesis and
degradation rates do not correlate within one treatment, consistent with their
independent regulation. When performing robustness analyses of the rate
estimates, we observed that most genes adhere to one of two major modes of
regulation, which we term synthesis- and degradation-independent regulation.
These two modes, in which only one of the rates has to be tightly set, while the
other one can assume various values, offer an efficient way for the cell to
respond to stimuli and re-establish proteostasis. We experimentally validate
degradation-independent regulation under oxidative stress for the heatshock
protein Ssa4.
PMID- 25111755
TI - Rapid peptidomic profiling of peritoneal fluid by MALDI-TOF mass spectrometry for
the identification of biomarkers of endometriosis.
AB - Peptidomic profiling of peritoneal fluid by Matrix Assisted Laser Desorption
Ionization-Time of Flight Mass Spectrometry (MALDI-TOF-MS) may represent a
promising, suitable, rapid method for early diagnosis and staging of
endometriosis. In a case-control study, peritoneal fluid was collected from 23
patients affected by endometriosis (eight minimal/mild endometriosis and 15
moderate/severe endometriosis) and six "endometriosis free" women undergoing
laparoscopy. MALDI-TOF mass spectra of the peptide fraction extracted from
peritoneal fluid samples lead to identify biomarkers potentially suitable for
discriminating between peritoneal fluid samples from women affected by
minimal/mild endometriosis and those from women affected by moderate/severe
endometriosis. Peptidomic analysis of peritoneal fluid samples may define
putative peptide biomarkers suitable for staging endometriosis and improve our
understanding of the pathogenesis of endometriosis.
PMID- 25111756
TI - Treatment of simple and complex endometrial non-atypical hyperplasia with natural
progesterone: response rate to different doses.
AB - The aim of this study is to evaluate the response rate to natural progesterone in
non-atypical endometrial hyperplasia and to identify the lowest effective dose. A
total of 197 patients of childbearing age with simple or complex hyperplasia were
retrospectively identified. The women were treated with a cyclic administration
of progesterone at different dosages (100 versus 200 versus 300 mg daily).
Endometrial biopsies were performed at 6, 12, 18 months. In comparing
progesterone to a regimen of no therapy, a significantly higher remission rate
was observed in the progesterone group than in the latter (95 versus 75%, p =
0.05 for simple hyperplasia; 89 versus 35%, p < 0.001 for complex hyperplasia).
Out of 60 women with simple hyperplasia, remission was observed in 9/11 (81.8%),
40/41 (97.5%) and 8/8 (100%) patients treated, respectively, with progesterone
100, 200 and 300 mg daily. Out of 72 women with complex hyperplasia, remission
was observed in 3/5 (60%), 49/53 (92.4%) and 12/14 (85.7%) patients treated with
progesterone 100, 200 and 300 mg daily, respectively. There was no statistically
significant difference in the response rate in the two groups, neither with
simple nor with complex hyperplasia. In conclusion, progesterone increased the
regression rate of both simple and complex hyperplasia.
PMID- 25111757
TI - Deferred intravitreal triamcinolone in diabetic eyes after phacoemulsification.
AB - PURPOSE: Evaluation of diabetic macular edema (DME) after phacoemulsification by
optical coherence tomography (OCT) and the use of deferred intravitreal
triamcinolone acetonide (IVTA) as a therapy. METHODS: This was an institutional,
nonrandomized, retrospective study. Within a period of 18 months, 5,684 eyes
underwent phacoemulsification in our department, 1,634 of which were diabetic.
Eight weeks after surgery, 55 out of 1,634 diabetic eyes that had undergone
phacoemulsification developed DME and were treated with a 3.2 mg IVTA injection.
The mean best-corrected visual acuity (BCVA) and mean central macular thickness
(CMT) were measured before and after phacoemulsification and 3 months after IVTA.
RESULTS: The mean BCVA at baseline, after phacoemulsification, and 3 months after
deferred IVTA was 49.0+/-17.7, 53.7+/-17.4, and 66.36+/-20.66, respectively. The
mean CMT for the same endpoints was 268.9+/-76.3, 554.6+/-137.8, and 275.0+/-76.3
MUm, respectively. Eyes were subdivided into 2 subgroups: eyes with a previous
history of DME and eyes with de novo DME. Three months after deferred IVTA, there
was a statistically significant difference between these 2 subgroups in BCVA
(P<0.001) and in CMT (P=0.002). The OCT features before and after IVTA defined 2
subgroups of DME, with respect to cyst color and symmetry and OS/IS line
integrity after IVTA. CONCLUSIONS: Our data suggest that DME progresses after
uncomplicated phacoemulsification in diabetic eyes and that IVTA is an
appropriate therapeutic tool. The response to IVTA treatment depends on previous
history of DME and its OCT profile.
PMID- 25111758
TI - Modulation of hunger and satiety: hormones and diet.
AB - PURPOSE OF REVIEW: To highlight recent research developments relating to the
effects of, and interactions between, hormones and diet, as well as underlying
mechanisms, on appetite, energy intake and body weight. For this purpose,
clinically relevant English language articles were reviewed from October 2012 to
April 2014. RECENT FINDINGS: The mechanisms underlying nutrient-induced energy
intake suppression differ between dietary protein and lipid. High-fat, energy
dense diets compromise the satiating effects of gut hormones, and, therefore,
promote further overconsumption. These effects are mediated by changes in the
signalling in both peripheral and central pathways, and may only be partially
reversible by dietary restriction. Additional factors, including probiotics, meal
related factors (e.g., eating speed and frequency), circadian influences and gene
polymorphisms, also modify energy intake and eating behaviour. SUMMARY: Research
continues to unravel the pathways and mechanisms underlying the nutrient-induced
and diet-induced regulation of energy intake, as well as the changes, both
peripherally and in the central nervous system, brought about by the consumption
of high-fat, energy-dense diets. Much further work is required to translate this
knowledge into novel, and effective, approaches for the management and treatment
of obesity and associated metabolic disorders.
PMID- 25111759
TI - Blue native-PAGE analysis of membrane protein complexes in Porphyromonas
gingivalis.
AB - Membrane complexes of Porphyromonas gingivalis were analyzed using two
dimensional-blue native-PAGE. The molecular mass of the gingipain complexes, RgpA
and Kgp, ranged from 450 kDa to greater than 1200 kDa, and did not change in
single rgpA and kgp mutants indicating that the proteolytically processed
polyproteins were independently capable of forming complexes. The outer membrane
protein, LptO, which is essential for gingipain secretion, was found in up to
seven different complex sizes. PG0026, also important for secretion, was observed
to interact with the largest LptO complex [VII] at 480 kDa, supporting a
cooperative role in secretion. Two pro-form RgpB intermediates formed a complex
before cleavage of their C-terminal secretion signal domains (CTDs) such that
complex formation may occur during secretion and processing. This may also be the
case for other CTD-proteins as not only modified, mature RgpB, but also CPG70 was
found to exist as multi-subunit complexes. RagA and RagB were observed in three
different complex sizes. Elimination of the abundant gingipains enabled the
identification of many inner and outer membrane protein complexes:
TonB:ExbB:ExbD, Omp85, P51:PG2168, PorK:PorN, PG0056, PG0241, PG1430 and five
proposed respiratory chain complexes (Mmd, Nqr, Rnf, Frd/Sdh and Atp). BIOLOGICAL
SIGNIFICANCE: Porphyromonas gingivalis is a major oral pathogen associated with
chronic periodontitis in humans. Secreted gingipains are considered major
virulence factors of this pathogen and are secreted by a newly described type IX
secretion system. This work has used 2D-BN-PAGE and MS to demonstrate that mature
gingipains can independently form complexes and that substrate intermediates and
mature secreted proteins of the type IX secretion system form multi-subunit
complexes. Based on this work we propose that the substrates of this secretion
system are secreted as large multi-subunit protein complexes. Two known important
components of the secretion machinery, PG0026 and the integral outer membrane
protein, LptO, were found to interact which would anchor PG0026 to the outer
membrane and perhaps aid in the function of PG0026 to cleave the CTD from
secreted substrates. The work has also identified more than 100 membrane proteins
forming multi-subunit complexes.
PMID- 25111760
TI - Superficial dopants allow growth of silicone nanofilaments on hydroxyl-free
substrates.
AB - We report new types of silicone nanostructures by a gas-phase reaction of
trichloromethylsilane: 1-D silicone nanofilaments with a raveled end and silicone
nanoteeth. Filaments with a raveled end are obtained on poly(vinyl chloride),
which is superficially doped with the detergent Span 20. Silicone nanoteeth grow
on sodium chloride using dibutyl phthalate as superficial dopant. Without
dopants, no structures are observed. The dopants are identified by mass
spectroscopy and the silicone nanostructures are analyzed by infrared
spectroscopy and energy-dispersive analysis of X-rays. The growth of silicone
nanostructures on a hydrophobic substrate (poly(vinyl chloride)/Span 20) and a
substrate free of hydroxyl groups (sodium chloride/dibutyl phthalate) questions
the currently discussed mechanisms for the growth of 1-D silicone nanofilaments,
which is discussed. We suggest superficial doping as an alternative pretreatment
method to oxidizing activation and prove this principle by the successful coating
of copper, which is superficially doped with Span 20.
PMID- 25111762
TI - Reorientation osteotomy for the atypical clasp thumb in children with
arthrogryposis.
AB - Congenital thumb contractures are a well described but complex deformity to
manage. Thumb contractures are common in patients with arthrogryposis. Many
patients with arthrogryposis develop a supination, adduction, and flexion
contracture at the thumb carpometacarpal join. Despite some thumb function, their
thumb position and contracted first webspace precludes effective pinch or grasp,
with the thumb opposing only to the palmar space. An extension, reorientation
metacarpal osteotomy that places thumb in an efficient position has the potential
to improve function in of these patients. This report provides a new
classification system for congenital thumb deformities that can dictate
management based upon thumb joint positions. We describe a previously unreported,
arthrogrypotic thumb contracture that can be managed with an extension/pronation
metacarpal osteotomy with simultaneous widening of the first webspace.
PMID- 25111763
TI - Laboratory and field efficacy of entomopathogenic fungi for the management of the
sweetpotato weevil, Cylas formicarius (Coleoptera: Brentidae).
AB - The sweetpotato weevil, Cylas formicarius (F.) (Coleoptera: Brentidae), is one of
the most important pests of sweet potatoes in the world. With free trade between
the United States and the U.S.-controlled Mariana Islands, C. formicarius has
spread along with this commodity. Because of the cryptic nature of the larvae and
nocturnal activity of the adults, and the cancellation of long-residual
pesticides, this pest has become increasingly difficult to control. Therefore,
the present study sought to explore and to compare the effectiveness of
Metarhizium brunneum F52 (90ml a.i./ha), Beauveria bassiana GHA (40ml a.i./ha),
spinosad (90g a.i./ha), azadirachtin (1484ml a.i./ha), B. bassiana+M. brunneum
(20ml a.i./ha+45ml a.i./ha), B. bassiana+azadirachtin (20ml a.i./ha+742ml
a.i./ha), B. bassiana+spinosad (20ml a.i./ha+45ml a.i./ha), M.
brunneum+azadirachtin (45ml a.i./ha+742ml a.i./ha) and M. brunneum+spinosad (45ml
a.i./ha+45 grams a.i./ha) in controlling this pest in both the laboratory and the
field. The treatment with B. bassiana+M. brunneum was the most effective in
reducing tuber damage by C. formicarius, producing the highest yields. The most
adult cadavers were found in plots treated with the combination of two fungi.
This combined fungal formulation appears to be appropriate for the practical
control of C. formicarius on sweet potatoes.
PMID- 25111761
TI - Optimization of sentinel lymph node mapping in bladder cancer using near-infrared
fluorescence imaging.
AB - BACKGROUND AND OBJECTIVES: Unlike other cancers, the Sentinel Lymph Node (SLN)
procedure in bladder cancer requires special attention to the injection
technique. The aim of this study was to assess feasibility and to optimize tracer
injection technique for SLN mapping in bladder cancer patients using NIR
fluorescence imaging. METHODS: Twenty patients with invasive bladder cancer
scheduled for radical cystectomy were prospectively enrolled. Indocyanine green
(ICG) bound to human serum albumin (complex ICG:HSA; 500 uM) was injected
peritumourally to permit SLN mapping. ICG:HSA was first administrated serosally
(n = 5), and subsequently mucosally by cystoscopic injection (n = 15). In the
last cohort of 12 patients treated with cystoscopic injection, the bladder was
kept filled with saline for at least 15 min. RESULTS: Fluorescent lymph nodes
were observed only in the patient group with cystoscopic injection of ICG:HSA.
Filling of the bladder post-injection was of added value to promote drainage of
ICG:HSA to the lymph nodes, and in 11 of these 12 patients (92%) one or more NIR
fluorescent lymph nodes were identified. CONCLUSIONS: The current study
demonstrates proof-of-principle of using NIR fluorescence imaging for SLN
identification in bladder cancer. Cystoscopic injection with distension of the
bladder appears optimal for SLN mapping.
PMID- 25111765
TI - Template-derived carbon: an unexpected promoter for the creation of strong
basicity on mesoporous silica.
AB - Template-derived carbon is demonstrated to effectively promote the creation of
strong basicity on mesoporous silica, for the first time. New materials owning
ordered mesoporous structure, strong basicity, and excellent catalytic activity
are thus successfully constructed at low temperatures, which are impossible to
achieve using conventional methods.
PMID- 25111766
TI - Reply to comment: Asociacion de Hemato-Oncologia Pediatrica de Centro America
(AHOPCA): a model for sustainable development in pediatric oncology.
PMID- 25111767
TI - A cell-surface-anchored ratiometric fluorescent probe for extracellular pH
sensing.
AB - Accurate sensing of the extracellular pH is a very important yet challenging task
in biological and clinical applications. This paper describes the development of
an amphiphilic lipid-DNA molecule as a simple yet useful cell-surface-anchored
ratiometric fluorescent probe for extracellular pH sensing. The lipid-DNA probe,
which consists of a hydrophobic diacyllipid tail and a hydrophilic DNA strand, is
modified with two fluorescent dyes; one is pH-sensitive as pH indicator and the
other is pH-insensitive as an internal reference. The lipid-DNA probe showed
sensitive and reversible response to pH change in the range of 6.0-8.0, which is
suitable for most extracellular studies. In addition, based on simple hydrophobic
interactions with the cell membrane, the lipid-DNA probe can be easily anchored
on the cell surface with negligible cytotoxicity, excellent stability, and unique
ratiometric readout, thus ensuring its accurate sensing of extracellular pH.
Finally, this lipid-DNA-based ratiometric pH indicator was successfully used for
extracellular pH sensing of cells in 3D culture environment, demonstrating the
potential applications of the sensor in biological and medical studies.
PMID- 25111768
TI - Selective uptake of cylindrical poly(2-oxazoline) brush-antiDEC205 antibody-OVA
antigen conjugates into DEC-positive dendritic cells and subsequent T-cell
activation.
AB - To achieve specific cell targeting by various receptors for oligosaccharides or
antibodies, a carrier must not be taken up by any of the very many different
cells and needs functional groups prone to clean conjugation chemistry to derive
well-defined structures with a high biological specificity. A polymeric
nanocarrier is presented that consists of a cylindrical brush polymer with poly-2
oxazoline side chains carrying an azide functional group on each of the many side
chain ends. After click conjugation of dye and an anti-DEC205 antibody to the
periphery of the cylindrical brush polymer, antibody-mediated specific binding
and uptake into DEC205(+) -positive mouse bone marrow-derived dendritic cells
(BMDC) was observed, whereas binding and uptake by DEC205(-) negative BMDC and
non-DC was essentially absent. Additional conjugation of an antigen peptide
yielded a multifunctional polymer structure with a much stronger antigen-specific
T-cell stimulatory capacity of pretreated BMDC than application of antigen or
polymer-antigen conjugate.
PMID- 25111770
TI - The development of time-based prospective memory in childhood: the role of
working memory updating.
AB - This large-scale study examined the development of time-based prospective memory
(PM) across childhood and the roles that working memory updating and time
monitoring play in driving age effects in PM performance. One hundred and ninety
seven children aged 5 to 14 years completed a time-based PM task where working
memory updating load was manipulated within individuals using a dual task design.
Results revealed age-related increases in PM performance across childhood.
Working memory updating load had a negative impact on PM performance and
monitoring behavior in older children, but this effect was smaller in younger
children. Moreover, the frequency as well as the pattern of time monitoring
predicted children's PM performance. Our interpretation of these results is that
processes involved in children's PM may show a qualitative shift over development
from simple, nonstrategic monitoring behavior to more strategic monitoring based
on internal temporal models that rely specifically on working memory updating
resources. We discuss this interpretation with regard to possible trade-off
effects in younger children as well as alternative accounts.
PMID- 25111771
TI - Thirty-day readmission rates after PCI in a metropolitan center in Europe:
incidence and impact on prognosis.
AB - INTRODUCTION: Thirty-day readmission rates after percutaneous coronary
intervention (PCI) have been related to adverse prognosis, and represent one of
the most investigated indicators of quality of care. These data, however, derive
from non-European centers evaluating all-cause readmissions, without
stratification for diagnosis. METHODS: All consecutive patients undergoing PCI at
our center from January 2009 to December 2011 were enrolled. Thirty-day
readmissions related to postinfarction angina, myocardial infarction, unstable
angina or heart failure were defined as acute coronary syndrome (ACS) or heart
failure rehospitalizations. Major cardiac adverse event (MACE) was the primary
outcome, and its single components (death, myocardial infarction and repeated
revascularization) the secondary ones. RESULTS: A total of 1192 patients were
included; among them, 53 (4.7%) were readmitted within 30 days, and 25 (2.1%)
were classified as ACS/heart failure related. During hospitalization, patients
with ACS/heart failure readmissions were more likely to suffer a periprocedural
myocardial infarction (22 vs. 4%; P = 0.012), and to undergo PCI at 30 days (52
vs. 0.5%; P < 0.001). Logistic regression analysis indicated that periprocedural
myocardial infarction represented the only independent predictor of an ACS/heart
failure readmission [odds ratio (OR) 4.5; 1.1-16.8; P = 0.047]. After a median
follow-up of 787 days (434-1027; first and third quartiles), patients with a 30
day ACS/heart failure readmission experienced higher rates of MACE, all-cause
death and myocardial infarction (64 vs. 21%, P < 0.001; 28 vs. 6%, P = 0.017; and
20 vs. 2.7%, P < 0.001, respectively). Cox multivariate analysis indicated that
ACS/heart failure 30-day readmissions were independently related to an increased
risk of all-cause death (OR 3.3; 1.1-8.8; P = 0.02), differently from 30-day non
ACS/heart failure readmissions (OR 3.1; 0.7-12.9; P = 0.12). CONCLUSION: Thirty
day readmissions after PCI in an Italian center are infrequent, and only those
patients with ACS/heart failure show a detrimental impact on prognosis who have
periprocedural myocardial infarction as the only independent predictor.
PMID- 25111772
TI - Rat models reveal differences in cardiocirculatory profile between Takotsubo
syndrome and acute myocardial infarction.
AB - AIMS: Takotsubo syndrome, also known as stress-induced cardiomyopathy, is an
important differential diagnosis in patients presenting with chest pain and is
associated with significant morbidity and mortality. Beyond adrenergic
overstimulation the pathophysiology behind Takotsubo is poorly known and the
syndrome cannot be differentiated from acute myocardial infarction (AMI) by non
invasive tests. Despite the facts that Takotsubo syndrome and AMI may differ in
many important aspects and that potential mechanistic similarities and/or
differences between Takotsubo syndrome and AMI have not been established,
Takotsubo syndrome patients are treated according to guidelines developed for AMI
and acute heart failure. The aim of this article was to assess whether cardiac
function and hemodynamic indices differ between rat models of Takotsubo syndrome
and AMI. METHODS: Male Sprague-Dawley rats were randomized to the Takotsubo
syndrome (50 mg/kg intraperitoneally isoprenaline) or AMI [permanent left
anterior descending coronary artery (LAD) ligation] models. Two hours post
isoprenaline or LAD ligation, arterial and intraventricular pressures were
recorded and cardiac function was studied by echocardiography. In another subset
of Takotsubo syndrome rats, pharmacological intervention aimed at maintaining
systolic blood pressure more than 90 mmHg with either norepinephrine or
phenylephrine was compared with saline. RESULTS: Left ventricular end-diastolic
pressure was significantly lower and estimates of cardiac function were
significantly better in Takotsubo syndrome rats compared with AMI rats.
Vasopressor treatment was associated with increased mortality in Takotsubo
syndrome rats (P < 0.05). CONCLUSION: Takotsubo syndrome and AMI are associated
with different cardiocirculatory profiles. Extrapolation of treatment strategies
across the syndromes may therefore not be appropriate.
PMID- 25111773
TI - Usefulness of EuroSCORE systems for risk stratification.
AB - Risk stratification of patients undergoing open-heart surgery or percutaneous
interventions may help physicians select the best individual management of
patients with advanced heart disease.European System for Cardiac Operative Risk
Evaluation (EuroSCORE) is an easy-to-calculate, clinical scoring system which has
been developed for coronary surgery and applied in various cardiological
settings. Recently, the EuroSCORE II model has been launched with the aim of
improving the stratification performance over the first model.In the present
study, we review the available scientific data on the use of EuroSCORE systems in
patients undergoing surgical or percutaneous procedures.
PMID- 25111774
TI - Coronary plaque ulceration documented at sequential angiography and confirmed by
optical coherence tomography in a patient with recurrent acute coronary syndrome.
AB - : A 51-year-old man was hospitalized for recurrence of acute coronary syndrome
after few months. Coronary angiography during first hospitalization showed no
significant coronary stenosis, while the second time, right coronary artery
presented an expansion at the proximal segment. Optical coherence tomography
documented a long fibroatheroma with an ulceration and residual white thrombus.
PMID- 25111769
TI - Recognition and repair of chemically heterogeneous structures at DNA ends.
AB - Exposure to environmental toxicants and stressors, radiation, pharmaceutical
drugs, inflammation, cellular respiration, and routine DNA metabolism all lead to
the production of cytotoxic DNA strand breaks. Akin to splintered wood, DNA
breaks are not "clean." Rather, DNA breaks typically lack DNA 5'-phosphate and 3'
hydroxyl moieties required for DNA synthesis and DNA ligation. Failure to resolve
damage at DNA ends can lead to abnormal DNA replication and repair, and is
associated with genomic instability, mutagenesis, neurological disease, ageing
and carcinogenesis. An array of chemically heterogeneous DNA termini arises from
spontaneously generated DNA single-strand and double-strand breaks (SSBs and
DSBs), and also from normal and/or inappropriate DNA metabolism by DNA
polymerases, DNA ligases and topoisomerases. As a front line of defense to these
genotoxic insults, eukaryotic cells have accrued an arsenal of enzymatic first
responders that bind and protect damaged DNA termini, and enzymatically tailor
DNA ends for DNA repair synthesis and ligation. These nucleic acid transactions
employ direct damage reversal enzymes including Aprataxin (APTX), Polynucleotide
kinase phosphatase (PNK), the tyrosyl DNA phosphodiesterases (TDP1 and TDP2), the
Ku70/80 complex and DNA polymerase beta (POLbeta). Nucleolytic processing enzymes
such as the MRE11/RAD50/NBS1/CtIP complex, Flap endonuclease (FEN1) and the
apurinic endonucleases (APE1 and APE2) also act in the chemical "cleansing" of
DNA breaks to prevent genomic instability and disease, and promote progression of
DNA- and RNA-DNA damage response (DDR and RDDR) pathways. Here, we provide an
overview of cellular first responders dedicated to the detection and repair of
abnormal DNA termini.
PMID- 25111776
TI - Highly efficient fluorescent interstrand photo-crosslinking of DNA duplexes
labeled with 5-fluoro-4-thio-2'-o-methyluridine.
AB - The formation of a fluorescent photoadduct between 5-fluoro-4-thiouridine ((FS)
U), in the sequence context 5'-A(FS) UA-3' and incorporated into a synthetic
oligonucleotide either at its 3'- or 5'-end, and one of the thymines of the TAT
motif in a complementary target DNA strand led to photo-crosslinking of the two
strands for several oligonucleotide constructs. Enzymatic digestion, MS, UV, and
fluorescence spectral analyses of the interstrand crosslinked oligonucleotides
revealed the identity of the thymidine that participates in the photo
crosslinking reaction as well as the diastereomeric structures of the crosslinks.
The proposed pathways of interstrand photo-crosslinking are supported by
experiments with isotopically labeled oligonucleotide constructs and visualized
by means of molecular dynamics simulations.
PMID- 25111777
TI - A rare case of uterine rupture due to a placental site trophoblastic tumour in
the rudimentary horn.
PMID- 25111775
TI - Brief exposure to cigarette smoke impairs airway epithelial cell innate anti
viral defence.
AB - BACKGROUND: Human rhinovirus (hRV) infections commonly cause acute upper
respiratory infections and asthma exacerbations. Environmental cigarette smoke
exposure is associated with a significant increase in the risk for these
infections in children. OBJECTIVE: To determine the impact of short-term exposure
to cigarette smoke on innate immune responses of airway epithelial cells infected
with hRV. METHODS: A human bronchial epithelial cell line (HBEC-3KT) was exposed
to cigarette smoke extract (CSE) for 30 min and subsequently infected with hRV
serotype 1B. Viral-induced cytokine release was measured with AlphaLISA and viral
replication quantified by shed viral titer and intracellular viral copy number
24h post-infection. RESULTS: CSE induced a concentration-dependent decrease in
CXCL10 (p<0.001) and IFN-beta (p<0.001), with a 79% reduction at the highest dose
with an associated 3-fold increase in shed virus. These effects were maintained
when infection was delayed up to 24h post CSE exposure. Exogenous IFN-beta
treatment at t=0 after infection blunts the effects of CSE on viral replication
(p<0.05). CONCLUSION: A single exposure of 30 min to cigarette smoke has a
lasting impact on epithelial innate defence providing a plausible mechanism for
the increase in respiratory infections seen in children exposed to second-hand
tobacco smoke.
PMID- 25111778
TI - Theoretical investigation on carbon nucleation on nickel carbides at initial
stages of single-walled carbon nanotube formation.
AB - It is a long-standing controversy whether metal carbide clusters do exist during
the nucleation and growth process of single-walled carbon nanotubes (SWCNTs). In
the current work, we are trying to elucidate the carbon nucleation on nickel
carbides during the initial stages based on density functional theory calculated
formation energy and chemical potential for a series of Ni55Cn carbides (n is the
number of carbon atoms dissolved in the Ni55 cluster). It is found that the
formation energies of the Ni55Cn carbides decrease gradually with an increase of
dissolved carbon atomic numbers, meaning the Ni55Cn carbides are
thermodynamically stable. Meanwhile, the calculated chemical potentials indicate
that not only nickel carbides are preferentially formed during the initial stage
of the SWCNT nucleation, but also saturated nickel carbides may be able to exist
during the nucleation and growth process of SWCNTs. In addition, the nickel
carbides have a high selectivity for the formation of the carbon pentagon and
carbon structures with pentagon-incorporated end-edge according to the adsorption
energies. All of these findings provide opportunities in controlling the growth
of the SWCNTs.
PMID- 25111782
TI - A four-stage hybrid model for hydrological time series forecasting.
AB - Hydrological time series forecasting remains a difficult task due to its
complicated nonlinear, non-stationary and multi-scale characteristics. To solve
this difficulty and improve the prediction accuracy, a novel four-stage hybrid
model is proposed for hydrological time series forecasting based on the principle
of 'denoising, decomposition and ensemble'. The proposed model has four stages,
i.e., denoising, decomposition, components prediction and ensemble. In the
denoising stage, the empirical mode decomposition (EMD) method is utilized to
reduce the noises in the hydrological time series. Then, an improved method of
EMD, the ensemble empirical mode decomposition (EEMD), is applied to decompose
the denoised series into a number of intrinsic mode function (IMF) components and
one residual component. Next, the radial basis function neural network (RBFNN) is
adopted to predict the trend of all of the components obtained in the
decomposition stage. In the final ensemble prediction stage, the forecasting
results of all of the IMF and residual components obtained in the third stage are
combined to generate the final prediction results, using a linear neural network
(LNN) model. For illustration and verification, six hydrological cases with
different characteristics are used to test the effectiveness of the proposed
model. The proposed hybrid model performs better than conventional single models,
the hybrid models without denoising or decomposition and the hybrid models based
on other methods, such as the wavelet analysis (WA)-based hybrid models. In
addition, the denoising and decomposition strategies decrease the complexity of
the series and reduce the difficulties of the forecasting. With its effective
denoising and accurate decomposition ability, high prediction precision and wide
applicability, the new model is very promising for complex time series
forecasting. This new forecast model is an extension of nonlinear prediction
models.
PMID- 25111779
TI - Pleiotropic functions for transcription factor zscan10.
AB - The transcription factor Zscan10 had been attributed a role as a pluripotency
factor in embryonic stem cells based on its interaction with Oct4 and Sox2 in in
vitro assays. Here we suggest a potential role of Zscan10 in controlling
progenitor cell populations in vivo. Mice homozygous for a Zscan10 mutation
exhibit reduced weight, mild hypoplasia in the spleen, heart and long bones and
phenocopy an eye malformation previously described for Sox2 hypomorphs.
Phenotypic abnormalities are supported by the nature of Zscan10 expression in
midgestation embryos and adults suggesting a role for Zscan10 in either
maintaining progenitor cell subpopulation or impacting on fate choice decisions
thereof.
PMID- 25111780
TI - Shedding of a low pathogenic avian influenza virus in a common synanthropic
mammal--the cottontail rabbit.
AB - BACKGROUND: Cottontails (Sylvilagus spp.) are common mammals throughout much of
the U.S. and are often found in peridomestic settings, potentially interacting
with livestock and poultry operations. If these animals are susceptible to avian
influenza virus (AIV) infections and shed the virus in sufficient quantities they
may pose a risk for movement of avian influenza viruses between wildlife and
domestic animals in certain situations. METHODOLOGY/PRINCIPAL FINDINGS: To assess
the viral shedding potential of AIV in cottontails, we nasally inoculated
fourteen cottontails with a low pathogenic AIV (H4N6). All inoculated cottontails
shed relatively large quantities of viral RNA both nasally (<= 10(6.94) PCR EID50
equivalents/mL) and orally (<= 10(5.09) PCR EID50 equivalents/mL). However, oral
shedding tended to decline more quickly than did nasal shedding. No animals
showed any obvious signs of disease throughout the study. Evidence of a
serological response was found in all infected rabbits at 22 days post infection
in convalescent sera. CONCLUSIONS/SIGNIFICANCE: To our knowledge, cottontails
have not been previously assessed for AIV shedding. However, it was obvious that
they shed AIV RNA extensively via the nasal and oral routes. This is significant,
as cottontails are widely distributed throughout the U.S. and elsewhere. These
mammals are often found in highly peridomestic situations, such as farms, parks,
and suburban neighborhoods, often becoming habituated to human activities. Thus,
if infected these mammals could easily transport AIVs short distances.
PMID- 25111781
TI - Evolutionary stability in the asymmetric volunteer's dilemma.
AB - It is often assumed that in public goods games, contributors are either strong or
weak players and each individual has an equal probability of exhibiting
cooperation. It is difficult to explain why the public good is produced by strong
individuals in some cooperation systems, and by weak individuals in others.
Viewing the asymmetric volunteer's dilemma game as an evolutionary game, we find
that whether the strong or the weak players produce the public good depends on
the initial condition (i.e., phenotype or initial strategy of individuals). These
different evolutionarily stable strategies (ESS) associated with different
initial conditions, can be interpreted as the production modes of public goods of
different cooperation systems. A further analysis revealed that the strong player
adopts a pure strategy but mixed strategies for the weak players to produce the
public good, and that the probability of volunteering by weak players decreases
with increasing group size or decreasing cost-benefit ratio. Our model shows that
the defection probability of a "strong" player is greater than the "weak" players
in the model of Diekmann (1993). This contradicts Selten's (1980) model that
public goods can only be produced by a strong player, is not an evolutionarily
stable strategy, and will therefore disappear over evolutionary time. Our public
good model with ESS has thus extended previous interpretations that the public
good can only be produced by strong players in an asymmetric game.
PMID- 25111783
TI - Trimethoprim use before pregnancy and risk of congenital malformation: reanalyzed
using a case-crossover design and a case-time-control design.
AB - PURPOSE: Studies on the safety of drugs used during pregnancy are necessary and
important but prone to bias. Using cases as their own controls can reduce bias.
We used a case-crossover design and a case-time-control design to estimate the
risk of congenital malformation (CM) for children born to mothers who redeemed a
trimethoprim prescription shortly before pregnancy. METHODS: The study was based
on all live born singletons (N = 685 600) in Denmark whose mothers had available
information on prescriptions in the Danish National Prescription Registry between
1996 and 2008. We defined 1-3 months before pregnancy as a potential risk period
and 13-15 months before pregnancy as a reference period. Two other reference
periods were used (7-9 months before pregnancy and months 4-6 of pregnancy). The
case-crossover design is dependent on the assumption of a stable trimethoprim
prescription over the study period in the source population. To estimate the
trend of trimethoprim prescriptions, we used a control group comprising children
without CMs. RESULTS: Both study designs showed children had a higher risk of
overall CM [odds ratio of 1.66, 95% confidence interval (CI): 1.10-2.53 and 1.50,
95%CI: 0.66-3.38, respectively] if their mothers had a trimethoprim prescription
in the 3 months before pregnancy and subtypes of CM for example in the
musculoskeletal system, which were consistent to the previous findings from a
cohort study. CONCLUSIONS: This study corroborates that trimethoprim is a
potential teratogen when used 3 months before pregnancy and demonstrates the
value of case-only approaches for studying, for example, adverse effects of
antibiotics in reproductive epidemiology.
PMID- 25111784
TI - Hypomethylation of the paternally inherited LRRTM1 promoter linked to
schizophrenia.
AB - Epigenetic effects on psychiatric traits remain relatively under-studied, and it
remains unclear what the sizes of individual epigenetic effects may be, or how
they vary between different clinical populations. The gene LRRTM1 (chromosome
2p12) has previously been linked and associated with schizophrenia in a parent-of
origin manner in a set of affected siblings (LOD = 4.72), indirectly suggesting a
disruption of paternal imprinting at this locus in these families. From the same
set of siblings that originally showed strong linkage at this locus, we analyzed
99 individuals using 454-bisulfite sequencing, from whole blood DNA, to measure
the level of DNA methylation in the promoter region of LRRTM1. We also assessed
seven additional loci that would be informative to compare. Paternal identity-by
descent sharing at LRRTM1, within sibling pairs, was linked to their similarity
of methylation at the gene's promoter. Reduced methylation at the promoter showed
a significant association with schizophrenia. Sibling pairs concordant for
schizophrenia showed more similar methylation levels at the LRRTM1 promoter than
diagnostically discordant pairs. The alleles of common SNPs spanning the locus
did not explain this epigenetic linkage, which can therefore be considered as
largely independent of DNA sequence variation and would not be detected in
standard genetic association analysis. Our data suggest that hypomethylation at
the LRRTM1 promoter, particularly of the paternally inherited allele, was a risk
factor for the development of schizophrenia in this set of siblings affected with
familial schizophrenia, and that had previously showed linkage at this locus in
an affected-sib-pair context.
PMID- 25111787
TI - Transfer hydrogenation as a redox process in nucleotides.
AB - Using a combined theoretical and experimental strategy, the heats of
hydrogenation of the nucleotide bases uracil, thymine, cytosine, adenine, and
guanine have been determined. The most easily hydrogenated base is uracil,
followed by thymine and cytosine. Comparison of these hydrogenation enthalpies
with those of ketones and aldehydes derived from sugar models indicates the
possibility of near-thermoneutral hydrogen transfer between uracil and the sugar
phosphate backbone in oligonucleotides.
PMID- 25111786
TI - Salt appetite is reduced by a single experience of drinking hypertonic saline in
the adult rat.
AB - Salt appetite, the primordial instinct to favorably ingest salty substances,
represents a vital evolutionary important drive to successfully maintain body
fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague
Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid
intake tests. However, this appetitive stimulus was fundamentally transformed
into a powerfully aversive one by increasing the salt content of drinking fluid
from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS
similar to IS when given no choice in one-bottle tests and previous studies have
indicated that this may modify salt appetite. We thus investigated if a single 24
h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD)
altered salt preference. Here we show that 24 h of ingesting IS and HS solutions,
but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days
and 35 days later. Using two-bottle tests rats previously exposed to IS preferred
neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses
to sweet solutions (1% sucrose) were not different in two-bottle tests with
water, suggesting that salt was the primary aversive taste pathway recruited in
this model. Inducing thirst by subcutaneous administration of angiotensin II did
not overcome this salt aversion. We hypothesised that this behavior results from
altered gene expression in brain structures important in thirst and salt
appetite. Thus we also report here lasting changes in mRNAs for markers of
neuronal activity, peptide hormones and neuronal plasticity in supraoptic and
paraventricular nuclei of the hypothalamus following rehydration after both DH
and HS. These results indicate that a single experience of drinking HS is a
memorable one, with long-term changes in gene expression accompanying this
aversion to salty solutions.
PMID- 25111785
TI - Common and rare variant analysis in early-onset bipolar disorder vulnerability.
AB - Bipolar disorder is one of the most common and devastating psychiatric disorders
whose mechanisms remain largely unknown. Despite a strong genetic contribution
demonstrated by twin and adoption studies, a polygenic background influences this
multifactorial and heterogeneous psychiatric disorder. To identify susceptibility
genes on a severe and more familial sub-form of the disease, we conducted a
genome-wide association study focused on 211 patients of French origin with an
early age at onset and 1,719 controls, and then replicated our data on a German
sample of 159 patients with early-onset bipolar disorder and 998 controls.
Replication study and subsequent meta-analysis revealed two genes encoding
proteins involved in phosphoinositide signalling pathway (PLEKHA5 and PLCXD3). We
performed additional replication studies in two datasets from the WTCCC (764
patients and 2,938 controls) and the GAIN-TGen cohorts (1,524 patients and 1,436
controls) and found nominal P-values both in the PLCXD3 and PLEKHA5 loci with the
WTCCC sample. In addition, we identified in the French cohort one affected
individual with a deletion at the PLCXD3 locus and another one carrying a
missense variation in PLCXD3 (p.R93H), both supporting a role of the
phosphatidylinositol pathway in early-onset bipolar disorder vulnerability.
Although the current nominally significant findings should be interpreted with
caution and need replication in independent cohorts, this study supports the
strategy to combine genetic approaches to determine the molecular mechanisms
underlying bipolar disorder.
PMID- 25111789
TI - Low yield of outpatient serum folate testing: eleven years of experience.
PMID- 25111788
TI - White matter tractography in early psychosis: clinical and neurocognitive
associations.
AB - BACKGROUND: While many diffusion tensor imaging (DTI) investigations have noted
disruptions to white matter integrity in individuals with chronic psychotic
disorders, fewer studies have been conducted in young people at the early stages
of disease onset. Using whole tract reconstruction techniques, the aim of this
study was to identify the white matter pathology associated with the common
clinical symptoms and executive function impairments observed in young people
with psychosis. METHODS: We obtained MRI scans from young people with psychosis
and healthy controls. Eighteen major white matter tracts were reconstructed to
determine group differences in fractional anisotropy (FA), axial diffusivity (AD)
and radial diffusivity (RD) and then were subsequently correlated with
symptomatology and neurocognitive performance. RESULTS: Our study included 42
young people with psychosis (mean age 23 yr) and 45 healthy controls (mean age 25
yr). Compared with the control group, the psychosis group had reduced FA and AD
in the left inferior longitudinal fasciculus (ILF) and forceps major indicative
of axonal disorganization, reduction and/or loss. These changes were associated
with worse overall psychiatric symptom severity, increases in positive and
negative symptoms, and worse current levels of depression. The psychosis group
also showed FA reductions in the left superior longitudinal fasciculus that were
associated with impaired neurocognitive performance in attention and semantic
fluency. LIMITATIONS: Our analysis grouped 4 subcategories of psychosis together,
and a larger follow-up study comparing affective and nonaffective psychoses is
warranted. CONCLUSION: Our findings suggest that impaired axonal coherence in the
left ILF and forceps major underpin psychiatric symptoms in young people in the
early stages of psychosis.
PMID- 25111790
TI - Inhibin alpha-subunit (INHA) expression in adrenocortical cancer is linked to
genetic and epigenetic INHA promoter variation.
AB - Adrenocortical carcinoma (ACC) is a rare, but highly malignant tumor of unknown
origin. Inhibin alpha-subunit (Inha) knockout mice develop ACCs following
gonadectomy. In man, INHA expression varies widely within ACC tissues and its
circulating peptide inhibin pro-alphaC has been described as a novel tumor marker
for ACC. We investigated whether genetic and epigenetic changes of the INHA gene
in human ACC cause loss or variation of INHA expression. To this end, analyses of
INHA sequence, promoter methylation and mRNA expression were performed in human
adrenocortical tissues. Serum inhibin pro-alphaC levels were also measured in ACC
patients. INHA genetic analysis in 37 unique ACCs revealed 10 novel, heterozygous
rare variants. Of the 3 coding bases affected, one variant was synonymous and two
were missense variants: S72F and S184F. The minor allele of rs11893842 at -124 bp
was observed at a low frequency (24%) in ACC samples and was associated with
decreased INHA mRNA levels: 4.7+/-1.9 arbitrary units for AA, compared to 26+/-11
for AG/GG genotypes (P = 0.034). The methylation of four proximal INHA promoter
CpGs was aberrantly increased in five ACCs (47.7+/-3.9%), compared to normal
adrenals (18.4+/-0.6%, P = 0.0052), whereas the other 14 ACCs studied showed
diminished promoter methylation (9.8+/-1.1%, P = 0.020). CpG methylation was
inversely correlated to INHA mRNA levels in ACCs (r = -0.701, p = 0.0036), but
not associated with serum inhibin pro-alphaC levels. In conclusion, aberrant
methylation and common genetic variation in the INHA promoter occur in human ACCs
and are associated with decreased INHA expression.
PMID- 25111793
TI - Surgical clipping of a basilar perforator artery aneurysm: a case of avoiding
perforator sacrifice.
AB - BACKGROUND: Aneurysms arising from basilar perforator arteries are very rare. A
primary goal of surgery is always preservation of perforator flow. However, in
most surgically managed cases in the literature, sacrifice of the perforator was
reported. It is important for the literature to demonstrate that patency of the
perforator is an achievable goal. OBJECTIVE: To present the second reported case
of perforator flow preservation in the surgical management of basilar perforator
artery aneurysms. CLINICAL PRESENTATION: A 45-year-old woman presented with World
Federation of Neurologic Surgeons grade 1 subarachnoid hemorrhage. Digital
subtraction angiography ultimately revealed a 2-mm aneurysm of the basilar artery
arising from a perforator after an initially negative angiogram. Clipping was
performed with perforator patency confirmed on direct inspection and
intraoperative angiography. The patient's postoperative course was uneventful,
and postoperative magnetic resonance imaging (MRI) showed no evidence of
brainstem stroke. CONCLUSION: Although patency of the perforator is a rather
obvious goal of cerebrovascular surgery, the current literature does not reflect
an ability to do so in the case of basilar perforator aneurysms. We present only
the second reported case of maintenance of perforator flow after clipping of a
basilar perforator artery aneurysm.
PMID- 25111792
TI - Beta-2 adrenergic receptor (ADRB2) gene polymorphisms and the risk of asthma: a
meta-analysis of case-control studies.
AB - BACKGROUND AND OBJECTIVE: A number of studies have assessed the relationship
between beta-2 adrenergic receptor (ADRB2) gene polymorphisms and asthma risk.
However, the results are inconsistent. A meta-analysis that focused on the
association between asthma and all ADRB2 polymorphisms with at least three case
control studies was thus performed. METHODS: A literature search of the PubMed,
Embase, Web of Science, CNKI, and Wangfang databases was conducted. Odds ratios
with 95% confidence intervals were used to assess the strength of associations.
RESULTS: Arg16Gly, Gln27Glu, Thr164Ile, and Arg19Cys single nucleotide
polymorphisms (SNPs) were identified in 46 case-control studies. The results
showed that not all of the SNPs were associated with asthma in the overall
population. Significant associations were found for the Arg16Gly polymorphism in
the South American population via dominant model comparison (OR = 1.754, 95% CI =
1.179-2.609, I2 = 16.9%, studies = 2, case = 314, control = 237) in an
analysis stratified by ethnicity. For the Gln27Glu polymorphism, a protective
association was found in children via recessive model comparison (OR = 0.566, 95%
CI = 0.417-0.769, I2 = 0.0%, studies = 11, case = 1693, control = 502) and
homozygote genotype comparison (OR = 0.610, 95% CI = 0.434-0.856, I2 = 0.0%,
studies = 11, case = 1693, control = 1502), and in adults via dominant model
comparison (OR = 0.864, 95% CI = 0.768-0.971, I2 = 46.9%, n = 18, case = 3160,
control = 3433). CONCLUSIONS: None of the ADRB2 gene polymorphisms were
reproducibly associated with a risk of asthma across ethnic groups in the general
population.
PMID- 25111794
TI - A novel high-resolution single locus sequence typing scheme for mixed populations
of Propionibacterium acnes in vivo.
AB - The Gram-positive anaerobic bacterium Propionibacterium acnes is a prevalent
member of the normal skin microbiota of human adults. In addition to its
suspected role in acne vulgaris it is involved in a variety of opportunistic
infections. Multi-locus sequence-typing (MLST) schemes identified distinct
phylotypes associated with health and disease. Being based on 8 to 9 house
keeping genes these MLST schemes have a high discriminatory power, but their
application is time- and cost-intensive. Here we describe a single-locus sequence
typing (SLST) scheme for P. acnes. The target locus was identified with a genome
mining approach that took advantage of the availability of representative genome
sequences of all known phylotypes of P. acnes. We applied this SLST on a
collection of 188 P. acnes strains and demonstrated a resolution comparable to
that of existing MLST schemes. Phylogenetic analysis applied to the SLST locus
resulted in clustering patterns identical to a reference tree based on core
genome sequences. We further demonstrate that SLST can be applied to detect
multiple phylotypes in complex microbial communities by a metagenomic
pyrosequencing approach. The described SLST strategy may be applied to any
bacterial species with a basically clonal population structure to achieve easy
typing and mapping of multiple phylotypes in complex microbiotas. The P. acnes
SLST database can be found at http://medbac.dk/slst/pacnes.
PMID- 25111796
TI - Adsorption of small molecules on helical gold nanorods: a relativistic density
functional study.
AB - We study the adsorption of a variety of small molecules on helical gold nanorods
using relativistic density functional theory. We focus on Au40 which consists of
a central linear strand of five gold atoms with seven helical strands of five
gold atoms on a coaxial tube. All molecules preferentially adsorb at a single low
coordinated gold atom on the coaxial tube at an end of Au40. In most cases, there
is significant charge transfer (CT) between Au40 and the adsorbate, for CO and
NO2, there is CT from the Au40 to adsorbate while for all other molecules there
is CT from the adsorbate to Au40. Thus, Au40-adsorbate can be described as a
donor-accepter complex and we use charge decomposition analysis to better
understand the adsorption process. We determine the adsorption energy order to be
C5H5N >NO2 > CO > NH3 > CH2=CH2 > CH2=CH-CHO > NO > HC=CH > H2S > SO2 > HCN >
CH3OH > H2C=O > O2 > H2O > CH4 > N2. We find that the Au-C, Au-N, Au-S, and Au
O bonds are surprisingly strong, with clear implications for reactivity
enhancement of the adsorbate. The Au-H bond is relatively weak but, for
interactions via an H atom that is bonded to a carbon atom (e.g., CH4), we find
that there is large charge polarization of the Au-H-C moiety and partial
activation of the inert C-H bond. Although the Au-S and Au-O bonds are generally
weaker than the Au-C and Au-N bonds, we find that adsorption of H2S or H2O causes
greater distortion of Au40 in the binding region. However, the degree of
distortion is small and the helical structure is retained, demonstrating the
stability of the helical Au40 nanorod under perturbations.
PMID- 25111795
TI - An animal model for laryngotracheal injuries: an experimental study.
AB - OBJECTIVES/HYPOTHESIS: To establish an animal model for post-intubation
laryngotracheal injuries resulting in significant laryngotracheal insult without
compromising the survival of the animal for a minimum period of 12 weeks post
extubation. To study the extent of injury based on morphometric and
histopathological change seen at 12 weeks post-extubation. STUDY DESIGN:
Randomized block, single-blinded, experimental study. METHODS: Twelve New Zealand
white rabbits were used in this study. The rabbits were randomly divided into
three groups depending on the duration of intubation (6 hours, 4 hours, and 2
hours, respectively). The technique of intubation was standardized. Post
extubation, these rabbits were humanely sacrificed after observation for 12 weeks
or when they developed severe respiratory distress. The larynx and trachea were
subjected to gross and histopathological examination. RESULTS: Histopathological
examination and statistical analysis showed significant subglottic injury in all
group B rabbits (intubated for 4 hours), and all of them survived for 12 weeks.
CONCLUSION: In this study, an animal model for inducing and studying
laryngotracheal injuries due to endotracheal intubation has been established.
This study has the potential applications in research on etiopathogenesis and
management of post-intubation laryngotracheal injuries.
PMID- 25111797
TI - Broadening the spectrum of actin-based protrusive activity mediated by Arp2/3
complex-facilitated polymerization: motility of cytoplasmic ridges and tubular
projections.
AB - Arp2/3 complex-facilitated actin polymerization plays an essential role in a
variety of cellular functions including motility, adherence, endocytosis, and
trafficking. In the present study, we employ the sea urchin coelomocyte
experimental model system to test the hypotheses that Arp2/3 complex-nucleated
actin assembly mediates the motility of two unusual cellular protrusions; the
cytoplasmic ridges present during coelomocyte spreading, and inducible, tubular
shaped, and neurite-like projections. Our investigations couple pharmacological
manipulation employing inhibitors of actin polymerization and the Arp2/3 complex
with a wide array of imaging methods including digitally enhanced phase contrast,
DIC, and polarization light microscopy of live cells; conventional, confocal and
super-resolution light microscopy of fluorescently labeled cells; and scanning
and transmission electron microscopy. Taken together, the results of this study
indicate that Arp2/3 complex-facilitated actin polymerization underlies the
motility of coelomocyte cytoplasmic ridges and tubular projections, that these
processes are related to each other, and that they have been preliminarily
identified in other cell types. The results also highlight the broad spectrum of
actin-based protrusive activities dependent on the Arp2/3 complex and provide
additional insights into the pervasive nature of this ubiquitous actin nucleator.
Furthermore, we provide the first evidence of a possible mechanistic difference
between the impacts of the small molecule drugs BDM and CK666 on the Arp2/3
complex.
PMID- 25111798
TI - Direct imaging of functional networks.
AB - In blood-oxygenation-level-dependent functional magnetic resonance imaging
(fMRI), current methods typically acquire ~ 500,000 imaging voxels at each time
point, and then use computer algorithms to reduce this data to the coefficients
of a few hundred parcels or networks. This suggests that the amount of relevant
information present in the fMRI signal is relatively small, and presents an
opportunity to greatly improve the speed and signal to noise ratio (SNR) of the
fMRI process. In this work, a theoretical framework is presented for calculating
the coefficients of functional networks directly from highly undersampled fMRI
data. Using predefined functional parcellations or networks and a compact k-space
trajectory that samples data at optimal spatial scales, the problem of estimating
network coefficients is reformulated to allow for direct least squares
estimation, without Fourier encoding. By simulation, this approach is shown to
allow for acceleration of the imaging process under ideal circumstances by nearly
three orders of magnitude.
PMID- 25111800
TI - Methodology to improve design of accelerated life tests in civil engineering
projects.
AB - For reliability testing an Energy Expansion Tree (EET) and a companion Energy
Function Model (EFM) are proposed and described in this paper. Different from
conventional approaches, the EET provides a more comprehensive and objective way
to systematically identify external energy factors affecting reliability. The EFM
introduces energy loss into a traditional Function Model to identify internal
energy sources affecting reliability. The combination creates a sound way to
enumerate the energies to which a system may be exposed during its lifetime. We
input these energies into planning an accelerated life test, a Multi Environment
Over Stress Test. The test objective is to discover weak links and interactions
among the system and the energies to which it is exposed, and design them out. As
an example, the methods are applied to the pipe in subsea pipeline. However, they
can be widely used in other civil engineering industries as well. The proposed
method is compared with current methods.
PMID- 25111802
TI - Are there consistent grazing indicators in Drylands? Testing plant functional
types of various complexity in South Africa's Grassland and Savanna Biomes.
AB - Despite our growing knowledge on plants' functional responses to grazing, there
is no consensus if an optimum level of functional aggregation exists for
detecting grazing effects in drylands. With a comparative approach we searched
for plant functional types (PFTs) with a consistent response to grazing across
two areas differing in climatic aridity, situated in South Africa's grassland and
savanna biomes. We aggregated herbaceous species into PFTs, using hierarchical
combinations of traits (from single- to three-trait PFTs). Traits relate to life
history, growth form and leaf width. We first confirmed that soil and grazing
gradients were largely independent from each other, and then searched in each
biome for PFTs with a sensitive response to grazing, avoiding confounding with
soil conditions. We found no response consistency, but biome-specific optimum
aggregation levels. Three-trait PFTs (e.g. broad-leaved perennial grasses) and
two-trait PFTs (e.g. perennial grasses) performed best as indicators of grazing
effects in the semi-arid grassland and in the arid savanna biome, respectively.
Some PFTs increased with grazing pressure in the grassland, but decreased in the
savanna. We applied biome-specific grazing indicators to evaluate if differences
in grazing management related to land tenure (communal versus freehold) had
effects on vegetation. Tenure effects were small, which we mainly attributed to
large variability in grazing pressure across farms. We conclude that the striking
lack of generalizable PFT responses to grazing is due to a convergence of aridity
and grazing effects, and unlikely to be overcome by more refined classification
approaches. Hence, PFTs with an opposite response to grazing in the two biomes
rather have a unimodal response along a gradient of additive forces of aridity
and grazing. The study advocates for hierarchical trait combinations to identify
localized indicator sets for grazing effects. Its methodological approach may
also be useful for identifying ecological indicators in other ecosystems.
PMID- 25111799
TI - Effects of aging on genioglossus motor units in humans.
AB - The genioglossus is a major upper airway dilator muscle thought to be important
in obstructive sleep apnea pathogenesis. Aging is a risk factor for obstructive
sleep apnea although the mechanisms are unclear and the effects of aging on motor
unit remodeled in the genioglossus remains unknown. To assess possible changes
associated with aging we compared quantitative parameters related to motor unit
potential morphology derived from EMG signals in a sample of older (n = 11; >55
years) versus younger (n = 29; <55 years) adults. All data were recorded during
quiet breathing with the subjects awake. Diagnostic sleep studies (Apnea Hypopnea
Index) confirmed the presence or absence of obstructive sleep apnea. Genioglossus
EMG signals were analyzed offline by automated software (DQEMG), which estimated
a MUP template from each extracted motor unit potential train (MUPT) for both the
selective concentric needle and concentric needle macro (CNMACRO) recorded EMG
signals. 2074 MUPTs from 40 subjects (mean+/-95% CI; older AHI 19.6+/-9.9
events/hr versus younger AHI 30.1+/-6.1 events/hr) were extracted. MUPs detected
in older adults were 32% longer in duration (14.7+/-0.5 ms versus 11.1+/-0.2 ms;
P = 0.05), with similar amplitudes (395.2+/-25.1 uV versus 394.6+/-13.7 uV).
Amplitudes of CNMACRO MUPs detected in older adults were larger by 22% (62.7+/
6.5 uV versus 51.3+/-3.0 uV; P<0.05), with areas 24% larger (160.6+/-18.6 uV.ms
versus 130.0+/-7.4 uV.ms; P<0.05) than those detected in younger adults. These
results confirm that remodeled motor units are present in the genioglossus muscle
of individuals above 55 years, which may have implications for OSA pathogenesis
and aging related upper airway collapsibility.
PMID- 25111801
TI - Comparative 2D-DIGE proteomic analysis of bovine mammary epithelial cells during
lactation reveals protein signatures for lactation persistency and milk yield.
AB - Mammary gland is made up of a branching network of ducts that end with alveoli
which surrounds the lumen. These alveolar mammary epithelial cells (MEC) reflect
the milk producing ability of farm animals. In this study, we have used 2D-DIGE
and mass spectrometry to identify the protein changes in MEC during immediate
early, peak and late stages of lactation and also compared differentially
expressed proteins in MEC isolated from milk of high and low milk producing cows.
We have identified 41 differentially expressed proteins during lactation stages
and 22 proteins in high and low milk yielding cows. Bioinformatics analysis
showed that a majority of the differentially expressed proteins are associated in
metabolic process, catalytic and binding activity. The differentially expressed
proteins were mapped to the available biological pathways and networks involved
in lactation. The proteins up-regulated during late stage of lactation are
associated with NF-kappaB stress induced signaling pathways and whereas Akt, PI3K
and p38/MAPK signaling pathways are associated with high milk production mediated
through insulin hormone signaling.
PMID- 25111803
TI - Theory on the dynamics of oscillatory loops in the transcription factor networks.
AB - We develop a detailed theoretical framework for various types of transcription
factor gene oscillators. We further demonstrate that one can build genetic
oscillators which are tunable and robust against perturbations in the critical
control parameters by coupling two or more independent Goodwin-Griffith
oscillators through either -OR- or -AND- type logic. Most of the coupled
oscillators constructed in the literature so far seem to be of -OR- type. When
there are transient perturbations in one of the -OR- type coupled-oscillators,
then the overall period of the system remains constant (period-buffering) whereas
in case of -AND- type coupling the overall period of the system moves towards the
perturbed oscillator. Though there is a period-buffering, the amplitudes of
oscillators coupled through -OR- type logic are more sensitive to perturbations
in the parameters associated with the promoter state dynamics than -AND- type.
Further analysis shows that the period of -AND- type coupled dual-feedback
oscillators can be tuned without conceding on the amplitudes. Using these results
we derive the basic design principles governing the robust and tunable synthetic
gene oscillators without compromising on their amplitudes.
PMID- 25111804
TI - A computational approach to evaluate the androgenic affinity of iprodione,
procymidone, vinclozolin and their metabolites.
AB - Our research is aimed at devising and assessing a computational approach to
evaluate the affinity of endocrine active substances (EASs) and their metabolites
towards the ligand binding domain (LBD) of the androgen receptor (AR) in three
distantly related species: human, rat, and zebrafish. We computed the affinity
for all the selected molecules following a computational approach based on
molecular modelling and docking. Three different classes of molecules with well
known endocrine activity (iprodione, procymidone, vinclozolin, and a selection of
their metabolites) were evaluated. Our approach was demonstrated useful as the
first step of chemical safety evaluation since ligand-target interaction is a
necessary condition for exerting any biological effect. Moreover, a different
sensitivity concerning AR LBD was computed for the tested species (rat being the
least sensitive of the three). This evidence suggests that, in order not to over
/under-estimate the risks connected with the use of a chemical entity, further in
vitro and/or in vivo tests should be carried out only after an accurate
evaluation of the most suitable cellular system or animal species. The
introduction of in silico approaches to evaluate hazard can accelerate discovery
and innovation with a lower economic effort than with a fully wet strategy.
PMID- 25111805
TI - Responses of super rice (Oryza sativa L.) to different planting methods for grain
yield and nitrogen-use efficiency in the single cropping season.
AB - To break the yield ceiling of rice production, a super rice project was developed
in 1996 to breed rice varieties with super high yield. A two-year experiment was
conducted to evaluate yield and nitrogen (N)-use response of super rice to
different planting methods in the single cropping season. A total of 17 rice
varieties, including 13 super rice and four non-super checks (CK), were grown
under three N levels [0 (N0), 150 (N150), and 225 (N225) kg ha-1] and two
planting methods [transplanting (TP) and direct-seeding in wet conditions (WDS)].
Grain yield under WDS (7.69 t ha-1) was generally lower than TP (8.58 t ha-1).
However, grain yield under different planting methods was affected by N rates as
well as variety groups. In both years, there was no difference in grain yield
between super and CK varieties at N150, irrespective of planting methods.
However, grain yield difference was dramatic in japonica groups at N225, that is,
there was an 11.3% and 14.1% average increase in super rice than in CK varieties
in WDS and TP, respectively. This suggests that high N input contributes to
narrowing the yield gap in super rice varieties, which also indicates that super
rice was bred for high fertility conditions. In the japonica group, more N was
accumulated in super rice than in CK at N225, but no difference was found between
super and CK varieties at N0 and N150. Similar results were also found for N
agronomic efficiency. The results suggest that super rice varieties have an
advantage for N-use efficiency when high N is applied. The response of super rice
was greater under TP than under WDS. The results suggest that the need to further
improve agronomic and other management practices to achieve high yield and N-use
efficiency for super rice varieties in WDS.
PMID- 25111806
TI - Voice prosthetic biofilm formation and Candida morphogenic conversions in absence
and presence of different bacterial strains and species on silicone-rubber.
AB - Morphogenic conversion of Candida from a yeast to hyphal morphology plays a
pivotal role in the pathogenicity of Candida species. Both Candida albicans and
Candida tropicalis, in combination with a variety of different bacterial strains
and species, appear in biofilms on silicone-rubber voice prostheses used in
laryngectomized patients. Here we study biofilm formation on silicone-rubber by
C. albicans or C. tropicalis in combination with different commensal bacterial
strains and lactobacillus strains. In addition, hyphal formation in C. albicans
and C. tropicalis, as stimulated by Rothia dentocariosa and lactobacilli was
evaluated, as clinical studies outlined that these bacterial strains have
opposite results on the clinical life-time of silicone-rubber voice prostheses.
Biofilms were grown during eight days in a silicone-rubber tube, while passing
the biofilms through episodes of nutritional feast and famine. Biofilms
consisting of combinations of C. albicans and a bacterial strain comprised
significantly less viable organisms than combinations comprising C. tropicalis.
High percentages of Candida were found in biofilms grown in combination with
lactobacilli. Interestingly, L. casei, with demonstrated favorable effects on the
clinical life-time of voice prostheses, reduced the percentage hyphal formation
in Candida biofilms as compared with Candida biofilms grown in absence of
bacteria or grown in combination with R. dentocariosa, a bacterial strain whose
presence is associated with short clinical life-times of voice prostheses.
PMID- 25111808
TI - Solid support membrane-aerated catalytic biofilm reactor for the continuous
synthesis of (S)-styrene oxide at gram scale.
AB - Catalytic biofilms minimize reactant toxicity and maximize biocatalyst stability
in selective transformations of chemicals to value-added products in continuous
processes. The scaling up of such catalytic biofilm processes is challenging, due
to fluidic and biological parameters affording a special reactor design affecting
process performance. A solid support membrane-aerated biofilm reactor was
optimized and scaled-up to yield gram amounts of (S)-styrene oxide, a toxic and
instable high value chemical synthon. A sintered stainless steel membrane unit
was identified as an optimal choice as biofilm substratum and for high oxygen
mass transfer. A stable expanded polytetrafluoroethylene (ePTFE) membrane was
best suited for in situ substrate delivery and product extraction. For the
verification of scalability, catalytic biofilms of Pseudomonas sp. strain
VLB120DeltaC produced (S)-styrene oxide to an average concentration of 390 mM in
the organic phase per day (equivalent to 24.4 g Laq (-1) day(-1) ). This
productivity was gained by efficiently using the catalyst with an excellent
product yield on biomass of 13.6 gproduct gbiomass (-1) . This product yield on
biomass is in the order of magnitude reported for other continuous systems based
on artificially immobilized biocatalysts and is fulfilling the minimum
requirements for industrial biocatalytic processes. Overall, 46 g of (S)-styrene
oxide were produced and isolated (purity: 99%; enantiomeric excess [ee]: >99.8%.
yield: 30%). The productivity is in a similar range as in comparable small-scale
biofilm reactors highlighting the large potential of this methodology for
continuous bioprocessing of bulk chemicals and biofuels.
PMID- 25111809
TI - Anomalous one-electron processes in the chemistry of uranium nitrogen multiple
bonds.
AB - Novel reaction pathways are illustrated in the synthesis of uranium(IV),
uranium(V), and uranium(VI) monoimido complexes. In contrast to the
straightforward preparation of U(V)(?NSiMe3)[N(SiMe3)2]3 (1), the synthesis of a
uranium(V) tritylimido complex, U(V)(?NCPh3)[N(SiMe3)2]3 (4), from
U(III)[N(SiMe3)2]3 and Ph3CN3 was found to proceed through multiple one-electron
steps. Whereas the oxidation of 1 with copper(II) salts produced the uranium(VI)
monoimido complexes U(VI)(?NSiMe3)X[N(SiMe3)2]3 (X = Cl, Br), the reaction of 4
with CuBr2 undergoes sterically induced reduction to form the uranium(VI)
monoimido complex U(VI)(?NCPh3)Br2[N(SiMe3)2]2, demonstrating a striking
difference in reactivity based on imido substituent. The facile reduction of
compounds 1 and 4 with KC8 allowed for the synthesis of the uranium(IV) monoimido
derivatives, K[U(IV)(?NSiMe3)[N(SiMe3)2]3] (1-K) and K[U(IV)(?NCPh3)[N(SiMe3)2]3]
(4-K), respectively. In contrast, an analogous uranium(IV) monoimido complex,
K[U(IV)(?NPh(F))[N(SiMe3)Ph(F)]], Ph(F) = -pentafluorophenyl (6), was prepared
through a loss of N(SiMe3)2Ph(F) concomitant with one-electron oxidation of a
uranium(III) center. The uranium(IV) monoimido complexes were found to be
reactive toward electrophiles, demonstrating N-C and N-Si single bond formation.
One-electron reduction of nitrite provided a route to the uranium(VI) oxo/imido
complex, [Ph4P][U(VI)O(?NSiMe3)[N(SiMe3)2]3]. The energetics and electrochemical
processes involved in the various oxidation reactions are discussed. Finally,
comparison of the U(VI)(?NSiMe3)X[N(SiMe3)2]3, X = Cl, Br, complexes with the
previously reported U(VI)OX[N(SiMe3)2]3, X = Cl, Br, complexes suggested that the
donor strength of the trimethylsilylimido ligand is comparable to the oxo ligand.
PMID- 25111807
TI - An interferon response gene signature is associated with the therapeutic response
of hepatitis C patients.
AB - Infection with the hepatitis C virus (HCV) is a major cause of chronic liver
diseases and hepatocellular carcinoma worldwide, and thus represents a
significant public health problem. The type I interferon (IFN), IFNalpha, has
been successful in treating HCV-infected patients, but current IFN-based
treatment regimens for HCV have suboptimal efficacy, and relatively little is
known about why IFN therapy eliminates the virus in some patients but not in
others. Therefore, it is critical to understand the basic mechanisms that
underlie the therapeutic resistance to IFN action in HCV-infected individuals,
and there is an urgent need to identify those patients most likely to respond to
IFN therapy for HCV. To characterize the response of HCV-infected patients to
treatment with IFNalpha, the expression of an IFN-response gene signature
comprised of IFN-stimulated genes and genes that play an important role in the
innate immune response was examined in liver biopsies from HCV-infected patients
enrolled in a clinical trial. In the present study we found that the expression
of a subset of IFN-response genes was dysregulated in liver biopsy samples from
nonresponsive hepatitis C patients as compared with virologic responders. Based
on these findings, a statistical model was developed to help predict the response
of patients to IFN therapy, and compared to results obtained to the IL28 mutation
model, which is highly predictive of the response to IFN-based therapy in HCV
infected patients. We found that a model incorporating gene expression data can
improve predictions of IFN responsiveness compared to IL28 mutation status alone.
PMID- 25111810
TI - Infiltration of CD8+ lymphocytes is an independent prognostic factor of
biochemical failure-free survival in prostate cancer.
AB - BACKGROUNDS: The adaptive immune system can potentially have dual roles in cancer
development and progression by contributing to or suppressing tumor progression
and metastasis. The aim of this study was to evaluate the prognostic impact of
adaptive immune cells residing in different tumor compartments in prostate
cancer. METHODS: Tissue microarrays from 535 patients were constructed from
viable and representative tumor epithelial and stromal areas of primary PC
tumors, as well as from normal epithelial and stromal areas. Immunohistochemistry
was used to evaluate the density of CD3+, CD4+, CD8+, and CD20+ lymphocytes in
both tumor epithelial and tumor stromal areas. RESULTS: In univariate analysis, a
high density of CD3+ (P = 0.037) and CD8+ lymphocytes (P = 0.010) in tumor
epithelial areas was associated with significantly shorter biochemical failure
free survival. When analyzing both tumor epithelial and stromal tissue
compartments as one entity, similar relationships were observed for CD3+ (P =
0.046), CD4+ (P = 0.026), and CD8+ (P = 0.003) lymphocytes. In multivariate
analysis, high densities of CD8+ lymphocytes limited to tumor epithelial areas
(HR = 1.45, P = 0.032), as well as in the total tumor tissue (HR = 1.57, P =
0.007), were independent negative prognostic factors for biochemical failure-free
survival. CONCLUSIONS: A high density of CD8+ lymphocytes, especially in tumor
epithelial areas, is an independent negative prognostic factor for biochemical
failure-free survival.
PMID- 25111811
TI - Formaldehyde and heavy metal migration from rubber and metallic
packaging/utensils in Korea.
AB - The aim of this study was to determine the non-intentionally added substances-
formaldehyde and trace metals--at 4% acetic acid conditions in rubber and
metallic packaging/utensils. The temperature effect on migration in rubber and
metallic packaging/utensils was monitored at 60 degrees C and 100 degrees C
under acidic (pH < 3) circumstances. The concentrations were: formaldehyde--23.1
MUg kg-1, lead--13.41 MUg kg-1, cadmium--0.15 MUg kg-1, total arsenic--2.02 MUg
kg-1 and nickel--2.92 MUg kg-1 at 60 degrees C and formaldehyde--148.9 MUg kg-1,
lead--17.04 MUg kg-1, cadmium--0.14 MUg kg-1, total arsenic--7.25 MUg kg-1 and
nickel--8.7 MUg kg-1 at 100 degrees C. A significant difference was noticed in
formaldehyde and total arsenic between both temperatures (p < 0.01), which was
not present in other trace metals. In conclusion, formaldehyde and total arsenic
were more sensitive with cooking temperature than the other metals.
PMID- 25111812
TI - Genomic aspects of age-related macular degeneration.
AB - Age-related macular degeneration (AMD) is a major late-onset posterior eye
disease that causes central vision to deteriorate among elderly populations. The
predominant lesion of AMD is the macula, at the interface between the outer
retina and the inner choroid. Recent advances in genetics have revealed that
inflammatory and angiogenic pathways play critical roles in the pathophysiology
of AMD. Genome-wide association studies have identified ARMS2/HTRA1 and CFH as
major AMD susceptibility genes. Genetic studies for AMD will contribute to the
prevention of central vision loss, the development of new treatment, and the
maintenance of quality of vision for productive aging.
PMID- 25111813
TI - Microtubule stabilization attenuates vascular calcification through the
inhibition of osteogenic signaling and matrix vesicle release.
AB - Vascular calcification is a strong predictor of cardiovascular morbidity and
mortality, especially in individuals with chronic kidney disease or diabetes. The
mechanism of vascular calcification has remained unclear, however, and no
effective therapy is currently available. Our study was aimed at identifying the
role of dynamic remodeling of microtubule cytoskeletons in hyperphosphatemia
induced vascular calcification. Exposure of primary cultures of mouse vascular
smooth muscle cells (VSMCs) to inorganic phosphate (Pi) elicited ectopic
calcification that was associated with changes in tubulin dynamics, induction of
osteogenic signaling, and increased release of matrix vesicles. A microtubule
depolymerizing agent enhanced Pi-dependent calcification, whereas microtubule
stabilization by paclitaxel suppressed calcification both in VSMC cultures and in
an ex vivo culture system for the mouse aorta. The inhibition of Pi-stimulated
calcification by paclitaxel was associated with down-regulation of osteogenic
signal and attenuation of matrix vesicle release. Our results indicate that
microtubule plays a central role in vascular calcification, and that microtubule
stabilization represents a potential new approach to the treatment of this
condition.
PMID- 25111814
TI - MicroRNA-665 is involved in the regulation of the expression of the
cardioprotective cannabinoid receptor CB2 in patients with severe heart failure.
AB - The myocardial endocannabinoid system has been linked to stress response and
cardioprotection. In chronic heart failure (CHF), protective CB2 receptors are
markedly up-regulated while CB1 receptors are slightly down-regulated. We here
provide evidence that myocardial CB receptors are subject to microRNA regulation.
By a combined computational and experimental approach we show that CB1 receptors
are regulated by miR-494, and CB2 receptors are targeted by miR-665. Moreover, we
demonstrate that in CHF, miR-665 expression is significantly decreased while miR
494 is slightly increased, which is concordant with the previously reported
alterations of CB receptors. These results suggest that in CHF, altered
expression of specific miRNAs may contribute to a compensatory response of the
diseased myocardium.
PMID- 25111815
TI - Detection of in vivo protein tyrosine nitration in petite mutant of Saccharomyces
cerevisiae: consequence of its formation and significance.
AB - Protein tyrosine nitration (PTN) is a selective post-translational modification
often associated with physiological and pathophysiological conditions. Tyrosine
is modified in the 3-position of the phenolic ring through the addition of a
nitro group. In our previous study we first time showed that PTN occurs in vivo
in Saccharomyces cerevisiae. In the present study we observed occurrence of PTN
in petite mutant of S. cerevisiae which indicated that PTN is not absolutely
dependent on functional mitochondria. Nitration of proteins in S. cerevisiae was
also first time confirmed in immunohistochemical study using spheroplasts. Using
proteosomal mutants Rpn10Delta, Pre9Delta, we first time showed that the fate of
protein nitration in S. cerevisiae was not dependent on proteosomal clearing and
probably played vital role in modulating signaling cascades. From our study it is
evident that protein tyrosine nitration is a normal physiological event of S.
cerevisiae.
PMID- 25111816
TI - The role of calpain in an in vivo model of oxidative stress-induced retinal
ganglion cell damage.
AB - PURPOSE: In this study, we set out to establish an in vivo animal model of
oxidative stress in the retinal ganglion cells (RGCs) and determine whether there
is a link between oxidative stress in the RGCs and the activation of calpain, a
major part of the apoptotic pathway. MATERIALS AND METHODS: Oxidative stress was
induced in the RGCs of C57BL/6 mice by the intravitreal administration of 2,2'
azobis (2-amidinopropane) dihydrochloride (AAPH, 30mM, 2MUl). Control eyes were
injected with 2MUl of vehicle. Surviving Fluorogold (FG)-labeled RGCs were then
counted in retinal flat mounts. Double staining with CellROX and Annexin V was
performed to investigate the co-localization of free radical generation and
apoptosis. An immunoblot assay was used both to indirectly evaluate calpain
activation in the AAPH-treated eyes by confirming alpha-fodrin cleavage, and also
to evaluate the effect of SNJ-1945 (a specific calpain inhibitor: 4% w/v,
100mg/kg, intraperitoneal administration) in these eyes. RESULTS: Intravitreal
administration of AAPH led to a significant decrease in FG-labeled RGCs 7days
after treatment (control: 3806.7+/-575.2RGCs/mm(2), AAPH: 3156.1+/
371.2RGCs/mm(2), P<0.01). CellROX and Annexin V signals were co-localized in the
FG-labeled RGCs 24h after AAPH injection. An immunoblot assay revealed a cleaved
alpha-fodrin band that increased significantly 24h after AAPH administration.
Intraperitoneally administered SNJ-1945 prevented the cleavage of alpha-fodrin
and had a neuroprotective effect against AAPH-induced RGC death (AAPH: 3354.0+/
226.9RGCs/mm(2), AAPH+SNJ-1945: 3717.1+/-614.6RGCs/mm(2), P<0.01). CONCLUSION:
AAPH administration was an effective model of oxidative stress in the RGCs,
showing that oxidative stress directly activated the calpain pathway and induced
RGC death. Furthermore, inhibition of the calpain pathway protected the RGCs
after AAPH administration.
PMID- 25111817
TI - Genetic architecture of type 2 diabetes.
AB - Genome-wide association studies (GWAS) have identified over 70 loci associated
with type 2 diabetes (T2D). Most genetic variants associated with T2D are common
variants with modest effects on T2D and are shared with major ancestry groups. To
what extent the genetic component of T2D can be explained by common variants
relies upon the shape of the genetic architecture of T2D. Fine mapping utilizing
populations with different patterns of linkage disequilibrium and functional
annotation derived from experiments in relevant tissues are mandatory to track
down causal variants responsible for the pathogenesis of T2D.
PMID- 25111818
TI - The role of mutation of metabolism-related genes in genomic hypermethylation.
AB - Genetic mutations, metabolic dysfunction, and epigenetic misregulation are
commonly considered to play distinct roles in tumor development and maintenance.
However, intimate relationships between these mechanisms are now emerging. In
particular, mutations in genes for the core metabolic enzymes IDH, SDH, and FH
are significant drivers of diverse tumor types. In each case, the resultant
accumulation of particular metabolites inhibits TET enzymes responsible for
oxidizing 5-methylcytosine, leading to pervasive DNA hypermethylation.
PMID- 25111819
TI - Evidence for participation of GCS1 in fertilization of the starlet sea anemone
Nematostella vectensis: implication of a common mechanism of sperm-egg fusion in
plants and animals.
AB - It has been reported that GCS1 (Generative Cell Specific 1) is a transmembrane
protein that is exclusively expressed in sperm cells and is essential for gamete
fusion in flowering plants. The GCS1 gene is present not only in angiosperms but
also in unicellular organisms and animals, implying the occurrence of a common or
ancestral mechanism of GCS1-mediated gamete fusion. In order to elucidate the
common mechanism, we investigated the role of GCS1 in animal fertilization using
a sea anemone (Cnidaria), Nematostella vectensis. Although the existence of the
GCS1 gene in N. vectensis has been reported, the expression of GCS1 in sperm and
the role of GCS1 in fertilization are not known. In this study, we showed that
the GCS1 gene is expressed in the testis and that GCS1 protein exists in sperm by
in situ hybridization and proteomic analysis, respectively. Then we made four
peptide antibodies against the N-terminal extracellular region of NvGCS1. These
antibodies specifically reacted to NvGCS1 among sperm proteins on the basis of
Western analysis and potently inhibited fertilization in a concentration
dependent manner. These results indicate that sperm GCS1 plays a pivotal role in
fertilization, most probably in sperm-egg fusion, in a starlet sea anemone,
suggesting a common gamete-fusion mechanism shared by eukaryotic organisms.
PMID- 25111820
TI - Skeletal analysis and differential gene expression in Runx2/Osterix double
heterozygous embryos.
AB - The transcription factors, Runx2 and Osterix (Osx), act downstream in the BMP2
pathway, and they are essential for osteoblast differentiation and bone
formation. While Runx2 expression is normal in Osx-null mice, Osx is not
expressed in Runx2-null mice, indicating that Osx acts downstream of Runx2 during
bone formation. Runx2 and Osx are also independently regulated during bone
formation. To define the unknown correlation between Runx2 and Osx in the
regulation of bone formation, we analyzed the bone of Runx2/Osx double
heterozygotes generated by mating heterozygous Runx2 and Osx mice and elucidated
the differential gene expressions due to the lack of Runx2 and Osx in bone.
Compared to the Runx2 and Osx heterozygous embryos, Runx2/Osx double heterozygous
embryos showed reduced bone length in the humerus and femur as well as
hypoplastic or complete absence of the maxillary and palatine shelf, presphenoid
bone, zygomatic bone, and tympanic ring. Severe inward bending was observed in
the ribs and humerus. Histological analysis showed an expanded region of
hypertrophic chondrocytes and a reduced area of mineralized bones in the
Runx2/Osx double heterozygous embryos. DNA microarray analysis of the calvaria of
embryos allowed gene classification based on similarities in the upregulated and
downregulated expression patterns. Clusters 1 and 2 include 68 downregulated
genes and 18 upregulated genes, respectively, in the Runx2/Osx double
heterozygous embryos. Finally, the skeletal analysis and gene expression profiles
obtained by clustering may facilitate the understanding of the correlation
between Runx2 and Osx in skeletal development.
PMID- 25111821
TI - Somatic alterations and dysregulation of epigenetic modifiers in cancers.
AB - Genomic discovery efforts in patients with cancer have been critical in
identifying a recurrent theme of mutations in epigenetic modifiers. A number of
novel and exciting basic biological findings have come from this work including
the discovery of an enzymatic pathway for DNA cytosine demethylation, a link
between cancer metabolism and epigenetics, and the critical importance of post
translational modifications at specific histone residues in malignant
transformation. Identification of cancer cell dependency on a number of these
mutations has quickly resulted in the development of therapies targeting several
of these genetic alterations. This includes, the development of mutant-selective
IDH1 and IDH2 inhibitors, DOT1L inhibitors for MLL rearranged leukemias, EZH2
inhibitors for several cancer types, and the development of bromodomain
inhibitors for many cancer types--all of which are in early phase clinical
trials. In many cases, however, specific genetic targets linked to malignant
transformation following mutations in individual epigenetic modifiers are not yet
known. In this review we present functional evidence of how alterations in
frequently mutated epigenetic modifiers promote malignant transformation and how
these alterations are being targeted for cancer therapeutics.
PMID- 25111822
TI - Separating heart and brain: on the reduction of physiological noise from
multichannel functional near-infrared spectroscopy (fNIRS) signals.
AB - OBJECTIVE: Functional near-infrared spectroscopy (fNIRS) is an emerging technique
for the in vivo assessment of functional activity of the cerebral cortex as well
as in the field of brain-computer interface (BCI) research. A common challenge
for the utilization of fNIRS in these areas is a stable and reliable
investigation of the spatio-temporal hemodynamic patterns. However, the recorded
patterns may be influenced and superimposed by signals generated from
physiological processes, resulting in an inaccurate estimation of the cortical
activity. Up to now only a few studies have investigated these influences, and
still less has been attempted to remove/reduce these influences. The present
study aims to gain insights into the reduction of physiological rhythms in
hemodynamic signals (oxygenated hemoglobin (oxy-Hb), deoxygenated hemoglobin
(deoxy-Hb)). APPROACH: We introduce the use of three different signal processing
approaches (spatial filtering, a common average reference (CAR) method;
independent component analysis (ICA); and transfer function (TF) models) to
reduce the influence of respiratory and blood pressure (BP) rhythms on the
hemodynamic responses. MAIN RESULTS: All approaches produce large reductions in
BP and respiration influences on the oxy-Hb signals and, therefore, improve the
contrast-to-noise ratio (CNR). In contrast, for deoxy-Hb signals CAR and ICA did
not improve the CNR. However, for the TF approach, a CNR-improvement in deoxy-Hb
can also be found. SIGNIFICANCE: The present study investigates the application
of different signal processing approaches to reduce the influences of
physiological rhythms on the hemodynamic responses. In addition to the
identification of the best signal processing method, we also show the importance
of noise reduction in fNIRS data.
PMID- 25111823
TI - Identifying barriers to move to better health coverage: preferences for health
insurance benefits among the rural poor population in La Guajira, Colombia.
AB - Even though access to health insurance in Colombia has improved since the
implementation of the 1993 health reforms (Law 100), universal coverage has not
yet been accomplished. There is still a segment of the population under the low
income (subsidized) health insurance policy or without health insurance
altogether. The purpose of this research was to identify preferences and behavior
regarding health insurance among the subsidized rural population in La Guajira,
Colombia, and to understand why that population remains under the subsidized
health insurance policy. The field experiment gathered information from 400
households regarding their socioeconomic situation, health conditions, and
preferences for health insurance characteristics. Results suggest that the
surveyed population gives priority to expanded family coverage, physician and
hospital choice, and access to specialists, rather than to attributes associated
with co-payments or premiums. That indicates that people value healthcare
benefits and family coverage more than health insurance expenses, and policy
makers could use these preferences to enroll subsidized population into the
contributory regime.
PMID- 25111824
TI - Odor tracking in sharks is reduced under future ocean acidification conditions.
AB - Recent studies show that ocean acidification impairs sensory functions and alters
the behavior of teleost fishes. If sharks and other elasmobranchs are similarly
affected, this could have significant consequences for marine ecosystems
globally. Here, we show that projected future CO2 levels impair odor tracking
behavior of the smooth dogfish (Mustelus canis). Adult M. canis were held for 5
days in a current-day control (405 +/- 26 MUatm) and mid (741 +/- 22 MUatm) or
high CO2 (1064 +/- 17 MUatm) treatments consistent with the projections for the
year 2100 on a 'business as usual' scenario. Both control and mid CO2 -treated
individuals maintained normal odor tracking behavior, whereas high CO2 -treated
sharks significantly avoided the odor cues indicative of food. Control sharks
spent >60% of their time in the water stream containing the food stimulus, but
this value fell below 15% in high CO2 -treated sharks. In addition, sharks
treated under mid and high CO2 conditions reduced attack behavior compared to the
control individuals. Our findings show that shark feeding could be affected by
changes in seawater chemistry projected for the end of this century.
Understanding the effects of ocean acidification on critical behaviors, such as
prey tracking in large predators, can help determine the potential impacts of
future ocean acidification on ecosystem function.
PMID- 25111826
TI - Balance of apoptotic cell death and survival in allergic diseases.
AB - Allergic diseases result from over-reaction of the immune system in response to
exogenous allergens, where inflammatory cells have constantly extended longevity
and contribute to an on-going immune response in allergic tissues. Here, we
review disequilibrium in the death and survival of epithelial cells and
inflammatory cells in the pathological processes of asthma, atopic dermatitis,
and other allergic diseases.
PMID- 25111827
TI - The immune response of two microbial antigens delivered intradermally,
sublingually, or the combination thereof.
AB - A key consideration to produce a successful vaccine is the choice of appropriate
vaccination route. Though most vaccines are administered parenterally, this route
is not effective in producing a robust mucosal or cell-mediated response.
Intradermal and sublingual vaccinations have been explored recently as potential
needle-free immunization strategies. We explored intradermal and sublingual
routes as well as the combination of the two routes in eliciting both systemic
and mucosal immune responses. Mice were immunized intradermally or sublingually
with dmLT, a mutant of Escherichia coli heat-labile toxin. A systemic IgG
response is dominant in intradermal immunization while a mucosal IgA response is
dominant in sublingual immunization. When routes were combined, a synergistic
response was seen with high titers of anti-dmLT IgG and IgA. IpaB/IpaD antigens
of Shigella flexneri type III secretion system, were admixed with dmLT as
adjuvant and administered by each route alone or in combination. Again, the
intradermal route elicited a systemic response while the sublingual route
elicited a mucosal response. When combined, the routes produced a robust
synergistic response to both antigens that exhibited a balanced Th1/Th2 response.
These results provide a new potential needle-free immunization strategy that will
benefit low income countries and increase compliance in industrial countries.
PMID- 25111828
TI - Anti-Mullerian hormone is associated with extrauterine involvement and stage of
disease in patients with endometrial cancer.
AB - Our aim was to evaluate serum levels of anti-Mullerian hormone (AMH) and also
immunohistochemical (IHC) staining properties of AMH receptor type II (AMHRII) in
patients with endometrial cancer (EC) and a control group. Preoperatively, serum
levels of AMH were assessed and AMHRII expression was evaluated by
immunohistochemistry in a benign and malignant group. AMH serum levels of the
control group and EC patients were comparable. For EC patients, there was no
difference with respect to the AMH levels and tumour stage; grade; histological
type; deep myometrial invasion; lymphovascular space invasion or lymph node
involvement. However, AMH levels in patients with extrauterine involvement were
higher than patients with disease confined to the uterus. EC samples were more
likely to be stained positive for AMHRII than benign lesions. Also, as the stage
of the lesion worsens, the rate of IHC staining of AMHRII decreases. In
conclusion, AMHRII is expressed in normal endometrial cells as well as
endometrial cancer cells. AMH levels increase in EC, with extrauterine
involvement at least in locally advanced disease. Also AMH expression decreases
as the disease is staged-up.
PMID- 25111829
TI - Connecting carbon nanotubes to polyoxometalate clusters for engineering high
performance anode materials.
AB - Carbon nanotubes (CNTs) possess excellent structural and electronic properties
and have been widely investigated as anode materials. Polyoxometalates (POMs)
exhibit superior physical properties such as electronic versatility, redox
characteristics and unique molecular structures. In this paper, we report the
covalent modification of carbon nanotubes (CNTs) with organosilica-containing
polyoxometalate (POM) of [Bu4N]4[SiW11O39{O(SiCH2CH2CH2NH2.HCl)2}] (SiW11-NH2)
that leads to the formation of the nanocomposite material of CNTs-SiW11, which
has been characterized by FT-IR, XRD, HR-TEM, XPS and Raman spectrum, etc. At a
current density of 0.5 mA cm(-2), the application of CNTs-SiW11 nanocomposite as
anode material in lithium batteries exhibits the first discharge capacity of 1189
mA h g(-1), and the second discharge capacity of 650 mA h g(-1), which remains
stable up to 100 cycles. The CNTs-SiW11 nanocomposite exhibits high discharge
capacity, good capacity retention and cycling stability.
PMID- 25111830
TI - Effect of surface potential on extracellular matrix protein adsorption.
AB - Extracellular matrix (ECM) proteins, such as fibronectin, laminin, and collagen
IV, play important roles in many cellular behaviors, including cell adhesion and
spreading. Understanding their adsorption behavior on surfaces with different
natures is helpful for studying the cellular responses to environments. By
tailoring the chemical composition in binary acidic (anionic) and basic
(cationic) functionalized self-assembled monolayer (SAM)-modified gold
substrates, variable surface potentials can be generated. To examine how surface
potential affects the interaction between ECM proteins and substrates, a quartz
crystal microbalance with dissipation detection (QCM-D) was used. To study the
interaction under physiological conditions, the ionic strength and pH were
controlled using phosphate-buffered saline at 37 degrees C, and the zeta
potentials of the SAM-modified Au and protein were determined using an
electrokinetic analyzer and phase analysis light scattering, respectively. During
adsorption processes, the shifts in resonant frequency (f) and energy dissipation
(D) were acquired simultaneously, and the weight change was calculated using the
Kelvin-Voigt model. The results reveal that slightly charged protein can be
adsorbed on a highly charged SAM, even where both surfaces are negatively
charged. This behavior is attributed to the highly charged SAM, which polarizes
the protein microscopically, and the Debye interaction, as well as other short
range interactions such as steric force, hydrogen bonding, direct bonding,
charged domains within the protein structure, etc., that allow adsorption,
although the macroscopic electrostatic interaction discourages adsorption. For
surfaces with a moderate potential, proteins are not significantly polarized by
the surface, and the interaction can be predicted through simple electrostatic
attraction. Furthermore, surface-induced self-assembly of protein molecules also
affects the adsorbed structures and kinetics. The adsorbed layer properties, such
as rigidity and packing behaviors, were further investigated using the D-f plot
and phase detection microscopy (PDM) imaging.
PMID- 25111831
TI - Valuation, categories and attributes.
AB - Existing research on categories has only examined indirectly the value associated
with being a member of a category relative to the value of the set of attributes
that determine membership in that category. This study uses survey data to
analyze consumers' preferences for the "organic" label versus for the attributes
underlying that label. We found that consumers generally preferred products with
the category label to those with the attributes required for the organic label
but without the label. We also found that the value accorded to the organic label
increased with the number of attributes that an individual associated with the
category. Category membership nevertheless still had greater value than even that
of the sum of the attributes associated with it.
PMID- 25111832
TI - Vitamin D status among Thai school children and the association with 1,25
Dihydroxyvitamin D and parathyroid hormone levels.
AB - In several low latitude countries, vitamin D deficiency is emerging as a public
health issue. Adequate vitamin D is essential for bone health in rapidly growing
children. In the Thai population, little is known about serum 25-hydroxyvitamin D
[25(OH)D] status of infants and children. Moreover, the association between
25(OH)D and the biological active form of 1,25-dihydroxyvitamin D [1,25(OH)]2D is
not clear. The specific aims of this study were to characterize circulating serum
25(OH)D, 1,25(OH)2D and their determinants including parathyroid hormone (PTH),
age, sex, height and body mass index (BMI) in 529 school-aged Thai children aged
6-14 y. Adjusted linear regression analysis was performed to examine the impact
of age and BMI, and its interaction with sex, on serum 25(OH)D concentrations and
1,25(OH)2D concentrations. Serum 25(OH)D, 1,25(OH)2D and PTH concentrations
(geometric mean +/- geometric SD) were 72.7+/-1.2 nmol/L, 199.1+/-1.3 pmol/L and
35.0+/-1.5 ng/L, respectively. Only 4% (21 of 529) participants had a serum
25(OH)D level below 50 nmol/L. There was statistically significant evidence for
an interaction between sex and age with regard to 25(OH)D concentrations.
Specifically, 25(OH)D concentrations were 19% higher in males. Moreover, females
experienced a statistically significant 4% decline in serum 25(OH)D levels for
each increasing year of age (P = 0.001); no decline was seen in male participants
with increasing age (P = 0.93). When BMI, age, sex, height and serum 25(OH)D were
individually regressed on 1,25(OH)2D, height and sex were associated with
1,25(OH)2D with females exhibiting statistically significantly higher serum
1,25(OH)2D levels compared with males (P<0.001). Serum 1,25(OH)2D among our
sample of children exhibiting fairly sufficient vitamin D status were higher than
previous reports suggesting an adaptive mechanism to maximize calcium absorption.
PMID- 25111833
TI - Altered distribution of peripheral blood memory B cells in humans chronically
infected with Trypanosoma cruzi.
AB - Numerous abnormalities of the peripheral blood T cell compartment have been
reported in human chronic Trypanosoma cruzi infection and related to prolonged
antigenic stimulation by persisting parasites. Herein, we measured circulating
lymphocytes of various phenotypes based on the differential expression of CD19,
CD4, CD27, CD10, IgD, IgM, IgG and CD138 in a total of 48 T. cruzi-infected
individuals and 24 healthy controls. Infected individuals had decreased
frequencies of CD19+CD27+ cells, which positively correlated with the frequencies
of CD4+CD27+ cells. The contraction of CD19+CD27+ cells was comprised of IgG+IgD
, IgM+IgD- and isotype switched IgM-IgD- memory B cells, CD19+CD10+CD27+ B cell
precursors and terminally differentiated CD19+CD27+CD138+ plasma cells.
Conversely, infected individuals had increased proportions of CD19+IgG+CD27-IgD-
memory and CD19+IgM+CD27-IgD+ transitional/naive B cells. These observations
prompted us to assess soluble CD27, a molecule generated by the cleavage of
membrane-bound CD27 and used to monitor systemic immune activation. Elevated
levels of serum soluble CD27 were observed in infected individuals with Chagas
cardiomyopathy, indicating its potentiality as an immunological marker for
disease progression in endemic areas. In conclusion, our results demonstrate that
chronic T. cruzi infection alters the distribution of various peripheral blood B
cell subsets, probably related to the CD4+ T cell deregulation process provoked
by the parasite in humans.
PMID- 25111835
TI - Completed suicide with violent and non-violent methods in rural Shandong, China:
a psychological autopsy study.
AB - BACKGROUND: This study aims to describe the specific characteristics of completed
suicides by violent methods and non-violent methods in rural Chinese population,
and to explore the related factors for corresponding methods. METHODS: Data of
this study came from investigation of 199 completed suicide cases and their
paired controls of rural areas in three different counties in Shandong, China, by
interviewing one informant of each subject using the method of Psychological
Autopsy (PA). RESULTS: There were 78 (39.2%) suicides with violent methods and
121 (60.8%) suicides with non-violent methods. Ingesting pesticides, as a non
violent method, appeared to be the most common suicide method (103, 51.8%).
Hanging (73 cases, 36.7%) and drowning (5 cases, 2.5%) were the only violent
methods observed. Storage of pesticides at home and higher suicide intent score
were significantly associated with choice of violent methods while committing
suicide. Risk factors related to suicide death included negative life events and
hopelessness. CONCLUSIONS: Suicide with violent methods has different factors
from suicide with non-violent methods. Suicide methods should be considered in
suicide prevention and intervention strategies.
PMID- 25111836
TI - Ultrathin hexagonal hybrid nanosheets synthesized by graphene oxide-assisted
exfoliation of beta-Co(OH)2 mesocrystals.
AB - In the present study, we report the synthesis of a high-quality, single-crystal
hexagonal beta-Co(OH)2 nanosheet, exhibiting a thickness down to ten atomic
layers and an aspect ratio exceeding 900, by using graphene oxide (GO) as an
exfoliant of beta-Co(OH)2 nanoflowers. Unlike conventional approaches using ionic
precursors in which morphological control is realized by structure-directing
molecules, the beta-Co(OH)2 flower-like superstructures were first grown by a
nanoparticle-mediated crystallization process, which results in large 3D
superstructure consisting of ultrathin nanosheets interspaced by
polydimethoxyaniline (PDMA). Thereafter, beta-Co(OH)2 nanoflowers were chemically
exfoliated by surface-active GO under hydrothermal conditions into unilamellar
single-crystal nanosheets. In this reaction, GO acts as a two-dimensional (2D)
amphiphile to facilitate the exfoliation process through tailored interactions
between organic and inorganic molecules. Meanwhile, the on-site conjugation of GO
and Co(OH)2 promotes the thermodynamic stability of freestanding ultrathin
nanosheets and restrains further growth through Oswald ripening. The unique 2D
structure combined with functionalities of the hybrid ultrathin Co(OH)2
nanosheets on rGO resulted in a remarkably enhanced lithium-ion storage
performance as anode materials, maintaining a reversible capacity of 860 mA h g(
1) for as many as 30 cycles. Since mesocrystals are ubiquitous and rich in
morphological diversity, the strategy of the GO-assisted exfoliation of
mesocrystals developed here provides an opportunity for the synthesis of new
functional nanostructures that could bear importance in clean renewable energy,
catalysis, photoelectronics, and photonics.
PMID- 25111834
TI - Prevalence of HPV 16 and HPV 18 lineages in Galicia, Spain.
AB - Genetic variants of human papillomavirus types 16 and 18 (HPV16/18) could differ
in their cancer risk. We studied the prevalence and association with high-grade
cervical lesions of different HPV16/18 variant lineages in a case-control study
including 217 cases (cervical intraepithelial neoplasia grade 2 or grade 3 or
worse: CIN2 or CIN3+) and 116 controls (no CIN2 or CIN3+ in two-year follow-up).
HPV lineages were determined by sequencing the long control region (LCR) and the
E6 gene. Phylogenetic analysis of HPV16 confirmed that isolates clustered into
previously described lineages: A (260, 87.5%), B (4, 1.3%), C (8, 2.7%), and D
(25, 8.4%). Lineage D/lineage A strains were, respectively, detected in 4/82
control patients, 19/126 CIN3+ cases (OR = 3.1, 95%CI: 1.0-12.9, p = 0.04), 6/1
glandular high-grade lesions (OR = 123, 95%CI: 9.7-5713.6, p<0.0001), and 4/5
invasive lesions (OR = 16.4, 95%CI: 2.2-113.7, p = 0.002). HPV18 clustered in
lineages A (32, 88.9%) and B (4, 11.1%). Lineage B/lineage A strains were
respectively detected in 1/23 control patients and 2/5 CIN3+ cases (OR = 9.2,
95%CI: 0.4-565.4, p = 0.12). In conclusion, lineages A of HPV16/18 were
predominant in Spain. Lineage D of HPV16 was associated with increased risk for
CIN3+, glandular high-grade lesions, and invasive lesions compared with lineage
A. Lineage B of HPV18 may be associated with increased risk for CIN3+ compared
with lineage A, but the association was not significant. Large well-designed
studies are needed before the application of HPV lineage detection in clinical
settings.
PMID- 25111838
TI - Nanomechanical properties, SEM, and EDS microanalysis of dentin treated with 2.5%
titanium tetrafluoride, before and after an erosive challenge.
AB - The aim was to assess the nanohardness (H) and the reduced modulus of elasticity
(Er ) of 2.5% titanium tetrafluoride (TiF4 ) modified dentin, before and after an
erosive challenge with 0.3% citric acid (CA). Exposed dentin surfaces were
divided into two groups (n = 5): (1) Control-no dentin pretreatment with TiF4
prior to etching with CA, and (2) Experimental-dentin pretreatment with TiF4 +
CA. The H and the Er of intertubular dentin were measured using a triboindenter
at different time points: baseline for both groups, after using 2.5% TiF4 for the
experimental group, and after using CA for both the experimental and the control
groups. Scanning electron microscope and energy dispersive X-ray spectroscopy
(EDS) analysis of the dentin surfaces were undertaken at the same time points for
both groups. Two-way ANOVA for randomized block design was applied. There was
significant interaction between the application of the TiF4 solution and
different time points (p = 0.001 for H and p < 0.001 for Er ), identified by
Tukey's test. Erosive challenge provided a significant decrease in H and Er mean
values. The TiF4 solution caused a significant increase in H and Er values, but
no significant differences were found between post-TiF4 and post-CA application.
TiF4 application produced a precipitate surface layer on intertubular and
intratubular dentin. EDS analysis indicated the presence of titanium. The H and
Er of the dentin surface were greatly increased after application of 2.5% TiF4 .
TiF4 may modify the micromorphology of the dentin surface and produces an erosive
resistance surface.
PMID- 25111839
TI - Intermolecular interactions and 3D structure in cellulose-NaOH-urea aqueous
system.
AB - The dissolution of cellulose in NaOH/urea aqueous solution at low temperature is
a key finding in cellulose science and technology. In this paper, (15)N and
(23)Na NMR experiments were carried out to clarify the intermolecular
interactions in cellulose/NaOH/urea aqueous solution. It was found that there are
direct interactions between OH(-) anions and amino groups of urea through
hydrogen bonds and no direct interaction between urea and cellulose. Moreover,
Na(+) ions can interact with both cellulose and urea in an aqueous system. These
interactions lead to the formation of cellulose-NaOH-urea-H2O inclusion complexes
(ICs). (23)Na relaxation results confirmed that the formation of urea-OH(-)
clusters can effectively enhance the stability of Na(+) ions that attracted to
cellulose chains. Low temperature can enhance the hydrogen bonding interaction
between OH(-) ions and urea and improve the binding ability of the NaOH/urea/H2O
clusters that attached to cellulose chains. Cryo-TEM observation confirmed the
formation of cellulose-NaOH-urea-H2O ICs, which is in extended conformation with
mean diameter of about 3.6 nm and mean length of about 300 nm. Possible 3D
structure of the ICs was proposed by the M06-2X/6-31+G(d) theoretical
calculation, revealing the O3H...O5 intramolecular hydrogen bonds could remain in
the ICs. This work clarified the interactions in cellulose/NaOH/urea aqueous
solution and the 3D structure of the cellulose chain in dilute
cellulose/NaOH/urea aqueous solution.
PMID- 25111841
TI - Self-reported versus administrative identification of American Indian and Alaska
Native arrestees: effects on relative estimates of illicit drug use and alcohol
abuse.
AB - Arrestee Drug Abuse Monitoring program data were used to consider the effects of
two methods of racial classification upon estimates of illicit drug use and
alcohol abuse among American Indian/Alaska Native (AI/AN) arrestees. Overall,
compared to arrestees who self-identified as Black, White, Asian/Pacific
Islander, or Hispanic, arrestees self-identifying as AI/AN were most likely to be
identified administratively as something other than AI/AN. Results of 'difference
of difference' analyses indicate that differences in estimates of AI/AN versus
non-AI/AN arrestees' illicit drug use and alcohol abuse were much more extreme
when identification was based on administrative records than when based upon
arrestees' self-reports.
PMID- 25111840
TI - Land-bridge calibration of molecular clocks and the post-glacial Colonization of
Scandinavia by the Eurasian field vole Microtus agrestis.
AB - Phylogeography interprets molecular genetic variation in a spatial and temporal
context. Molecular clocks are frequently used to calibrate phylogeographic
analyses, however there is mounting evidence that molecular rates decay over the
relevant timescales. It is therefore essential that an appropriate rate is
determined, consistent with the temporal scale of the specific analysis. This can
be achieved by using temporally spaced data such as ancient DNA or by relating
the divergence of lineages directly to contemporaneous external events of known
time. Here we calibrate a Eurasian field vole (Microtus agrestis) mitochondrial
genealogy from the well-established series of post-glacial geophysical changes
that led to the formation of the Baltic Sea and the separation of the
Scandinavian peninsula from the central European mainland. The field vole
exhibits the common phylogeographic pattern of Scandinavian colonization from
both the north and the south, however the southernmost of the two relevant
lineages appears to have originated in situ on the Scandinavian peninsula, or
possibly in the adjacent island of Zealand, around the close of the Younger
Dryas. The mitochondrial substitution rate and the timescale for the genealogy
are closely consistent with those obtained with a previous calibration, based on
the separation of the British Isles from mainland Europe. However the result here
is arguably more certain, given the level of confidence that can be placed in one
of the central assumptions of the calibration, that field voles could not survive
the last glaciation of the southern part of the Scandinavian peninsula.
Furthermore, the similarity between the molecular clock rate estimated here and
those obtained by sampling heterochronous (ancient) DNA (including that of a
congeneric species) suggest that there is little disparity between the measured
genetic divergence and the population divergence that is implicit in our land
bridge calibration.
PMID- 25111842
TI - Health perceptions among urban American Indians with type II diabetes.
AB - Since the 1940s, American Indians (AIs) have increasingly urbanized, moving off
of reservations in large part due to federal policies of tribal termination and
relocation. Though previous AI research has largely focused on reservation
associated challenges, many of these same challenges persist among urban AI
populations. One mutual concern is the growing prevalence and incidence of type
II diabetes mellitus (T2DM). While behavioral, genetic, and socioeconomic
determinants of T2DM have been explored, much less is known about the influence
of cultural and psychosocial factors. Recent studies suggest that the way AIs
perceive diabetes may affect their health trajectory and explain their poor
prognosis. Through the use of the Illness Perception Questionnaire, we explored
this hypothesis in a pilot study of urban AI with T2DM living in Los Angeles
County. We found that the majority of participants have a neutral perception
about their diabetes: They view their condition to be long lasting yet treatable
and indicate reasonable understanding of its symptoms and progression. We also
identified "personal control," the level of perceived control one has over his or
her disease, as a strong correlate of overall illness perception and, thus, a
potentially useful psychological metric.
PMID- 25111843
TI - Client and provider views on access to care for substance-using American Indians:
perspectives from a Northern Plains urban clinic.
AB - In addition to disparities in rates of substance use problems, American Indians
(AIs) report multiple barriers to receiving treatment services. The present study
utilized intake questionnaire data and focus groups to gain perspectives from 152
clients (65% male, 35% female; mean age 30 years) and 6 female providers on
access to treatment for Northern Plains AIs in an urban, non-Native program. AI
clients acknowledged the need for treatment more often than did substance users
in general, but faced greater resource barriers. Both clients and providers
offered specific recommendations for improving access to substance use treatment
for AI populations in the Northern Plains.
PMID- 25111844
TI - The economics of vaccination.
AB - The market for vaccinations is widely believed to be characterized by market
failures, because individuals do not internalize the positive externalities that
their vaccination decisions may confer on other individuals. Francis (1997)
provided a set of assumptions under which the equilibrium vaccination pattern is
socially optimal. We show that his conditions are not necessary for the welfare
theorem to hold but that in general, the market yields inefficiently low
vaccination uptake. Equilibrium non-optimality may obtain if (i) agents can
recover from infection, (ii) vaccines are imperfect, (iii) individuals are ex
ante heterogeneous, (iv) vaccination timing is inflexible or (v) the planning
horizon is finite. Apart from the case with heterogeneity, inefficiencies result
from the presence of strategic interaction.
PMID- 25111845
TI - On-line monitoring of chemical reactions by using bench-top nuclear magnetic
resonance spectroscopy.
AB - Real-time nuclear magnetic resonance (NMR) spectroscopy measurements carried out
with a bench-top system installed next to the reactor inside the fume hood of the
chemistry laboratory are presented. To test the system for on-line monitoring, a
transfer hydrogenation reaction was studied by continuously pumping the reaction
mixture from the reactor to the magnet and back in a closed loop. In addition to
improving the time resolution provided by standard sampling methods, the use of
such a flow setup eliminates the need for sample preparation. Owing to the
progress in terms of field homogeneity and sensitivity now available with compact
NMR spectrometers, small molecules dissolved at concentrations on the order of 1
mmol L(-1) can be characterized in single-scan measurements with 1 Hz resolution.
Owing to the reduced field strength of compact low-field systems compared to that
of conventional high-field magnets, the overlap in the spectrum of different NMR
signals is a typical situation. The data processing required to obtain
concentrations in the presence of signal overlap are discussed in detail, methods
such as plain integration and line-fitting approaches are compared, and the
accuracy of each method is determined. The kinetic rates measured for different
catalytic concentrations show good agreement with those obtained with gas
chromatography as a reference analytical method. Finally, as the measurements are
performed under continuous flow conditions, the experimental setup and the flow
parameters are optimized to maximize time resolution and signal-to-noise ratio.
PMID- 25111847
TI - Clearing up cardiorenal confusion.
PMID- 25111846
TI - Advanced glycation end products increase carbohydrate responsive element binding
protein expression and promote cancer cell proliferation.
AB - Diabetic patients have increased levels of advanced glycation end products (AGEs)
and the role of AGEs in regulating cancer cell proliferation is unclear. Here, we
found that treating colorectal and liver cancer cells with AGEs promoted cell
proliferation. AGEs stimulated both the expression and activation of a key
transcription factor called carbohydrate responsive element binding protein
(ChREBP) which had been shown to promote glycolytic and anabolic activity as well
as proliferation of colorectal and liver cancer cells. Using siRNAs or the
antagonistic antibody for the receptor for advanced glycation end-products (RAGE)
blocked AGEs-induced ChREBP expression or cell proliferation in cancer cells.
Suppressing ChREBP expression severely impaired AGEs-induced cancer cell
proliferation. Taken together, these results demonstrate that AGEs-RAGE signaling
enhances cancer cell proliferation in which AGEs-mediated ChREBP induction plays
an important role. These findings may provide new explanation for increased
cancer progression in diabetic patients.
PMID- 25111848
TI - Kinetic study of the OH radical reaction with phenylacetylene.
AB - The reaction of the OH radical with phenylacetylene is studied over the 298-423 K
temperature range and 1-7.5 Torr pressure range in a quasi-static reaction cell.
The OH radical is generated by 266 nm photolysis of hydrogen peroxide (H2O2) or
355 nm photolysis of nitrous acid (HONO), and its concentration monitored using
laser-induced fluorescence. The measured reaction rates are found to strongly
depend on laser fluence at 266 nm. The 266 nm absorption cross-section of
phenylacetylene is measured to be 1.29 (+/-0.71) * 10(-17) cm(2), prohibiting any
accurate kinetic measurements at this wavelength. The rates are independent of
laser fluence at 355 nm with an average value of 8.75 (+/-0.73) * 10(-11) cm(3)
s(-1). The reaction exhibits no pressure or temperature dependence over the
studied experimental conditions and is much faster than the estimated values
presently used in combustion models. These results are consistent with the
formation of a short lifetime intermediate that stabilizes by collisional
quenching with the buffer gas. The structures of the most likely formed products
are discussed based on both the computed energies for the OH-addition
intermediates and previous theoretical investigations on similar chemical
systems.
PMID- 25111849
TI - Intriguing transmission electron microscopy images observed for perpendicularly
oriented cylindrical microdomains of block copolymers.
AB - Intriguing images of dislocation structures were observed by the transmission
electron microscopy (TEM) technique for hexagonally packed cylindrical
microdomains in a block copolymer (polystyrene-block-polyethylenebutylene-block
polystyrene triblock copolymer) film. The polystyrene (PS) cylinders were
embedded in the polyethylenebutylene (PEB) matrix and oriented perpendicular to
the surface of the thin section for the TEM observations. In order to understand
such strange dislocation structures, we applied an image processing technique
using two-dimensional Fourier transform (FT) and inverse Fourier transform (IFT)
methods. It was found that these intriguing images were not ascribed to real
dislocation structures but were fake ones due to the moire effect caused by the
overlapping of hexagons with a slightly mismatched orientation. Furthermore,
grain boundaries in the ultrathin section can be identified by image processing
using FT and IFT methods.
PMID- 25111850
TI - Electrophysiology-based detection of emergency braking intention in real-world
driving.
AB - OBJECTIVE: The fact that all human action is preceded by brain processes
partially observable through neuroimaging devices such as electroencephalography
(EEG) is currently being explored in a number of applications. A recent study by
Haufe et al (2011 J. Neural Eng. 8 056001) demonstrates the possibility of
performing fast detection of forced emergency brakings during driving based on
EEG and electromyography, and discusses the use of such neurotechnology for
braking assistance systems. Since the study was conducted in a driving simulator,
its significance regarding real-world applicability needs to be assessed.
APPROACH: Here, we replicate that experimental paradigm in a real car on a non
public test track. MAIN RESULTS: Our results resemble those of the simulator
study, both qualitatively (in terms of the neurophysiological phenomena observed
and utilized) and quantitatively (in terms of the predictive improvement
achievable using electrophysiology in addition to behavioral measures). Moreover,
our findings are robust with respect to a temporary secondary auditory task
mimicking verbal input from a fellow passenger. SIGNIFICANCE: Our study serves as
a real-world verification of the feasibility of electrophysiology-based detection
of emergency braking intention as proposed in Haufe et al (2011 J. Neural Eng. 8
056001).
PMID- 25111851
TI - Gonadotropin-releasing hormone agonist selectively augments thymopoiesis and
prevents cell apoptosis in LPS induced thymic atrophy model independent of
gonadal steroids.
AB - Lipopolysaccharide (LPS) causes acute thymic atrophy, a phenomenon that has been
linked to immune dysfunction and poor survival during sepsis. The systemic
response to LPS involves a rise in glucocorticoids and proinflammatory cytokines
which contribute greatly to thymic involution and apoptosis. Gonadotropin
releasing hormone (GnRH) analog exerts thymopoietic regulatory effects and
possesses immunostimulant properties. We determined whether leuprolide, a GnRH
analog can be useful in LPS induced thymic involution and apoptosis. Mice
injected with 100 MUg of LPS intraperitoneally led to involution of thymus, to
decrease of CD4(+)8(+) thymocyte subset, and to fragmentation of thymic DNA.
Leuprolide (100 MUg/mouse, s.c.) pretreatment significantly attenuated LPS
induced thymic atrophy, and also reduced LPS induced systemic rise in
corticosterone levels. The observed effect of leuprolide remained unaffected in
castrated and ovariectomized mice. Collectively, leuprolide has protective action
independent of gonadal steroids, which was mediated by blunting of the systemic
corticosteroid response in LPS induced thymic atrophy model.
PMID- 25111852
TI - Glucagon like peptide-1 attenuates bleomycin-induced pulmonary fibrosis,
involving the inactivation of NF-kappaB in mice.
AB - Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with high
mortality and poor prognosis. Previous studies confirmed that NF-kappaB plays a
critical role in the pathogenesis of pulmonary fibrosis and glucagon like peptide
1 (GLP-1) has a property of anti-inflammation by inactivation of NF-kappaB.
Furthermore, the GLP-1 receptor was detected in the lung tissues. Our aim was to
investigate the potential value and mechanisms of GLP-1 on BLM-induced pulmonary
fibrosis in mice. Mice with BLM-induced pulmonary fibrosis were treated with or
without GLP-1 administration. 28 days after BLM infusion, the number of total
cells, macrophages, neutrophils, lymphocytes, and the content of TGF-beta1 in
BALF were measured. Hematoxylin-eosin (HE) staining and Masson's trichrome (MT)
staining were performed. The Ashcroft score and hydroxyproline content were
analyzed. RT-qPCR and western blot were used to evaluate the expression of alpha
SMA and VCAM-1. The phosphorylation of NF-kappaB p65 was also assessed by western
blot. DNA binding of NF-kappaB p65 was measured through Trans(AM) p65
transcription factor ELISA kit. GLP-1 reduced inflammatory cell infiltration and
the content of TGF-beta1 in BLAF in mice with BLM injection. The Ashcroft score
and hydroxyproline content were decreased by GLP-1 administration. Meanwhile, BLM
induced overexpression of alpha-SMA and VCAM-1 were blocked by GLP-1 treatment in
mice. GLP-1 also reduced the ratio of phosphor-NF-kappaB p65/total-NF-kappaB p65
and NF-kappaB p65 DNA binding activity in BLM-induced pulmonary fibrosis in mice.
Our data found that BLM-induced lung inflammation and pulmonary fibrosis were
significantly alleviated by GLP-1 treatment in mice, possibly through
inactivation of NF-kappaB.
PMID- 25111854
TI - Think twice before prescribing custom-compounded bioidentical hormone therapy.
PMID- 25111853
TI - Tristetraprolin is involved in the glucocorticoid-mediated interleukin 8
repression.
AB - Glucocorticoids have been widely used in various inflammatory disorders, and the
transcriptional repression of inflammatory mediators has been considered to be
the main mechanism of action. However, a previous study showed that dexamethasone
inhibited interleukin 8 (IL-8) expression by promoting IL-8 mRNA decay, which
implies a posttranscriptional regulation. Nevertheless, by which mechanism
dexamethasone destabilized IL-8 mRNA was unclear. Another study indicated that an
RNA-binding protein, tristetraprolin (TTP), could be induced by dexamethasone.
TTP can bind to AU-rich elements (ARE) in the 3'-untranslated region of target
mRNAs and promotes mRNA degradation. So, we speculated that dexamethasone
destabilized IL-8 mRNA by upregulating TTP expression. Here, we report that
dexamethasone reduced IL-8 expression through destabilizing IL-8 mRNA in human
pulmonary microvascular endothelial cells (HPMECs). Dexamethasone stimulation
increased TTP mRNA and protein levels. TTP silencing led to mRNA stabilization
and protein upregulation of IL-8. These results provide the evidence that the
glucocorticoid, in HPMECs, inhibits IL-8 expression through TTP at the
posttranscriptional level.
PMID- 25111855
TI - Toward a better understanding of the relationship between vulvodynia and chronic
stressors.
PMID- 25111856
TI - Risks and effectiveness of compounded bioidentical hormone therapy: a case
series.
AB - After the publication of the Women's Health Initiative, attitudes towards
management of menopausal symptoms changed dramatically. One alternative that has
received much media attention is the use of bioidentical hormone therapy (BHT).
The media and celebrity endorsements have promoted a number of misconceptions
about the risks and benefits associated with the various forms of BHT. This
article will review the available evidence regarding the safety and efficacy of
BHT in comparison to conventional hormone therapy. We will also review several
cases seen in our midlife women's referral clinics, which demonstrate concerns
for the safety and efficacy of BHT, including unexplained endometrial cancer in
otherwise healthy BHT users. Due to the lack of sufficient data to support the
efficacy or safety of BHT, we recommend the use of United States Food and Drug
Administration-approved regimens in the management of menopausal symptoms.
PMID- 25111857
TI - Ex vivo protective effects of nicotinamide and 3-aminobenzamide on rat
synaptosomes treated with Abeta(1-42).
AB - Alzheimer's disease (AD) is the most common form of dementia and is characterized
by the presence of senile plaques and neurofibrillary tangles, along with
synaptic loss. The underlying mechanisms of AD are not clarified yet, but
oxidative stress and mitochondrial dysfunction are important factors.
Overactivation of poly(adenosine diphosphate ribose) polymerase-1 (PARP-1) enzyme
has been known to cause neuroinflammation and cell death in neurodegenerative
processes. The aim of the present study was to investigate the protective effects
of the PARP-1 inhibitors, 3-aminobenzamide (3-AB) and nicotinamide (NA), against
amyloid beta peptide (1-42) (Abeta(1-42))-induced oxidative damage and
mitochondrial reduction capacity on isolated synaptosomes. Rats were injected
intraperitoneally with 3-AB (30-100 mg kg(-1)), NA (100-500 mg kg(-1)) or with
saline for 7 days. Synaptosomes were incubated with 10-30 MUM Abeta(1-42) or
saline for 6 h at 37 degrees C. Ex vivo Abeta(1-42) treatment significantly
induced oxidative stress and mitochondrial dysfunction in synaptosomes of the
saline group, while synaptosomes of 3-AB and NA groups showed significant
decreases in lipid peroxidation, reactive oxygen species production and protein
oxidation. Moreover, both NA and 3-AB were able to improve the mitochondrial
reduction capacity against Abeta(1-42). These data suggest that NA and 3-AB may
have protective effects in neurodegenerative processes because of the reduced
levels of oxidative stress and the improvement of mitochondrial function.
PMID- 25111858
TI - The hypertriglyceridemia is associated with isolated impaired glucose tolerance
in subjects without insulin resistance.
AB - AIM OF THE STUDY: The objective of this study was to determine if
hypertriglyceridemia is associated with isolated impaired glucose tolerance in
subjects without insulin resistance. MATERIALS AND METHODS: A total of 365
apparently healthy individuals aged 20-65 years were enrolled in a population
based cross-sectional study. Subjects were allocated into the groups with and
without hypertriglyceridemia. Age, gender, body mass index, and waist
circumference were matched criteria. Individuals with impaired fasting glucose,
impaired fasting glucose+impaired glucose tolerance, diabetes, homeostasis model
assessment of insulin resistance index >= 2.5, and/or chronic illnesses such as
renal disease or malignancy were excluded. Hypertriglyceridemia was defined by
triglycerides levels >= 150 mg/dL. Impaired glucose tolerance was defined by
plasma glucose concentration 2-h post-load glucose >= 140 mg/dL <200 mg/dL.
Subjects with impaired glucose tolerance were required to have fasting plasma
glucose levels <100 mg/dL. Logistic regression analysis was used to compute the
odds ratio between hypertriglyceridemia (independent variable) and impaired
glucose tolerance (dependent variable). RESULTS: A total of 132 and 233 subjects
were allocated into the groups with and without hypertriglyceridemia,
respectively. The frequency of impaired glucose tolerance was 13.6% and 5.6% in
the individuals with and without hypertriglyceridemia, p = 0.01. The logistic
regression analysis adjusted by gender, blood pressure, and high-density
lipoprotein cholesterol showed that hypertriglyceridemia is significantly
associated with impaired glucose tolerance (OR 2.34; 95% CI: 1.02-5.32, p =
0.04). CONCLUSION: Results of this study indicate that hypertriglyceridemia is
independently associated with isolated impaired glucose tolerance in subjects
without insulin resistance.
PMID- 25111859
TI - Cisplatin/gemcitabine or oxaliplatin/gemcitabine in the treatment of advanced
biliary tract cancer: a systematic review.
AB - Cisplatin/gemcitabine association has been a standard of care for first-line
regimen in advanced biliary tract cancer nevertheless oxaliplatin/gemcitabine
regimen is frequently preferred. Because comparative effectiveness in clinical
outcomes of cisplatin- versus oxaliplatin-containing chemotherapy is not
available, a systematic review of studies assessing cisplatin/gemcitabine or
oxaliplatin/gemcitabine chemotherapies in advanced biliary tract cancer was
performed. Published studies evaluating cisplatin/gemcitabine or
oxaliplatin/gemcitabine in advanced biliary tract cancer were included. Each
study was weighted according to the number of patients included. The primary
objective was to assess weighted median of medians overall survival (mOS)
reported for both regimens. Secondary goals were to assess weighted median of
medians progression-free survival (mPFS) and toxic effects were pooled and
compared within each arm. Thirty-three studies involving 1470 patients were
analyzed. In total, 771 and 699 patients were treated by cisplatin/gemcitabine
and oxaliplatin/gemcitabine, respectively. Weighted median of mOS was 9.7 months
in cisplatin group and 9.5 months in oxaliplatin group. Cisplatin-based
chemotherapy was significantly associated with more grade 3 and 4 asthenia,
diarrhea, liver toxicity, and hematological toxicity. Sensitivity analysis
including only the studies with the standard regimen of cisplatin (25-35 mg/m(2)
administered on days 1 and 8) showed that the weighted median of mOS increased
from 9.7 to 11.7 months but Gem/CDDP regimen remained more toxic than Gemox
regimen. These results suggest that the Gem/CDDP regimen with cisplatin (25-35
mg/m(2)) administered on days 1 and 8 is associated with survival advantage than
Gemox regimen but with addition of toxicity.
PMID- 25111860
TI - Alkali-soluble polysaccharide, isolated from Lentinus edodes, induces apoptosis
and G2/M cell cycle arrest in H22 cells through microtubule depolymerization.
AB - The aim of the study was to evaluate the pro-apoptotic effects of polysaccharides
derived from Lentinus edodes and further elucidated the mechanisms of this
action. Our results demonstrated that marked morphological changes of apoptosis
were observed after treatment of L. edodes polysaccharides [Lentinan (LTN)].
Moreover, LTN-induced cell apoptosis was characterized by a rapid stimulation of
reactive oxygen species production, the loss of mitochondrial membrane potential
and an increase in intracellular concentration of Ca(2+) . In addition, the
results of the haematoxylin and eosin and TUNEL assay further confirmed that LTN
induced apoptosis in vivo. Furthermore, flow cytometry analysis showed that LTN
could arrest the cell cycle at G2/M phase, and immunofluorescence showed LTN
caused disruption of microtubule. These results suggest that disruption of
cellular microtubule network, arrest of the cell cycle at G2/M phase and
induction of apoptosis may be one of the possible mechanisms of anti-tumour
effect of LTN.
PMID- 25111861
TI - The Yes-associated protein controls the cell density regulation of Hedgehog
signaling.
AB - The evolutionarily conserved Hedgehog (Hh) signaling pathway is essential for
correct embryogenesis and is misregulated in several malignancies. In cell
culture, Hh-sensitive cells display a striking dependence on cell density with
active Hh signaling requiring cell-to-cell contact. As the Hippo/YAP system is
tightly linked to cell density control and contact inhibition, we investigated
the cross-talk between the two pathways. Our data reveal that the suppression of
Hh signaling in the absence of cellular contacts is independent of primary cilia
and is mediated by the YAP oncogene. Overexpression of YAP blocks Hh signaling
whereas RNA interference-mediated knockdown of YAP enhances Hh/GLI activity.
Despite this negative regulation, Hh signaling promotes YAP activity through post
transcriptional mechanisms, resulting in a negative feedback loop. In vivo, we
found strong nuclear YAP immunoreactivity restricted to compartments with low Hh
pathway activity in human and mouse pancreatic cancer. Finally, we identified
protease-activated receptors (PARs) as molecules being able to override the
inverse Hippo/Hh regulation, potentially giving tumors a mechanism to utilize
both oncogenic pathways in parallel.Oncogenesis (2014) 3, e112;
doi:10.1038/oncsis.2014.27; published online 11 August 2014.
PMID- 25111862
TI - Selective repression of the oncogene cyclin D1 by the tumor suppressor miR-206 in
cancers.
AB - MicroRNAs (miRNAs) are deregulated in cancer and have been shown to exhibit both
oncogenic and tumor suppressive functions. Although the functional effects of
several miRNAs have been elucidated, those of many remain to be discovered. In
silico analysis identified microRNA-206 (miR-206) binding sites in the 3'
untranslated regions (3'-UTR) of both the mouse and human CCND1 gene. Cyclin D1
is a recognized oncogene involved in direct phosphorylation of the retinoblastoma
(Rb) protein and promoting cell cycle transition from G1 to S. miR-206
specifically binds to the CCND1 3'-UTR and mediates reduction of both cyclin D1
protein and mRNA. Expression of miR-206 induced a G1 arrest and a decrease in
cell proliferation in breast cancer cells. Ectopic expression of miRNA-resistant
cyclin D1 was able to reverse the miR-206-induced decrease in cell proliferation.
Therefore, we identified miR-206 as an activator of cell cycle arrest resulting
in a decrease in cell proliferation that is dependent on the inhibition of cyclin
D1. Interestingly, prostatic cancer (PCa) cells express low levels of miR-206
resulting in deregulated cyclin D1 expression compared with non-transformed
primary prostatic epithelial cells (PrEC). Finally, we demonstrate that cyclin D1
is regulated by miR-206 in PrEC but not in PCa cells and this is due to the
absence of a CCND1 3'-UTR in these cells. This suggests that miR-206-based anti
cyclin D1 targeted therapy would be beneficial in cancers where cyclin D1 is
overexpressed and contains a 3'-UTR.
PMID- 25111864
TI - Anatomy. The oldest child of Mother Medicine.
PMID- 25111863
TI - PSGR promotes prostatic intraepithelial neoplasia and prostate cancer xenograft
growth through NF-kappaB.
AB - Prostate-specific G-protein-coupled receptor (PSGR), a member of the olfactory
subfamily of G-protein-coupled receptors, is specifically expressed in human
prostate tissue and overexpressed in prostate cancer (PCa). This expression
pattern suggests a possible role in PCa initiation and progression. We developed
a PSGR transgenic mouse model driven by a probasin promoter and investigated the
role of PSGR in prostate malignancy. Overexpression of PSGR induced a chronic
inflammatory response that ultimately gave rise to premalignant mouse prostate
intraepithelial neoplasia lesions in later stages of life. PSGR-overexpressing
LnCaP cells in prostate xenografts formed larger tumors compared with normal
LnCaP cancer cells, suggesting a role of PSGR in the promotion of tumor
development. Furthermore, we identified nuclear factor-kappaB (NF-kappaB) or RELA
as a key downstream target activated by PSGR signaling. We also show that this
regulation was mediated in part by the phosphatidylinositol-3-kinase/Akt
(PI3K/AKT) pathway, highlighting a collaborative role between PI3K/AKT and NF
kappaB during tumor inflammation downstream of PSGR in the initial phases of
prostate disease.Oncogenesis (2014) 3, e114; doi:10.1038/oncsis.2014.29;
published online 11 August 2014.
PMID- 25111866
TI - The role of ghrelin in metabolic regulation.
AB - PURPOSE OF REVIEW: To discuss recent research on the role of ghrelin in the
regulation of carbohydrate and lipid metabolism in the context of its wider role
in regulating energy balance. RECENT FINDINGS: Ghrelin possesses a range of
centrally and peripherally mediated metabolic actions influencing insulin glucose
homeostasis and fatty acid metabolism and appetite. Although acyl ghrelin was
previously thought to be the active hormone, recent evidence suggests that des
acyl ghrelin also possesses activity, and the enzyme ghrelin-O-acyl transferase
regulates their interconversion. In partnership with insulin and leptin, ghrelin
defends against energy deficit by enhancing hunger, conserving carbohydrate and
promoting fat oxidation. In the postprandial state, it contributes to satiety,
energy storage and favours glucose oxidation. New research suggests a range of
new roles including addictive behaviours, cardiovascular protection,
neuroprotection and regeneration and perhaps the ageing process. SUMMARY: Ghrelin
functions primarily as a short-term metabolic switch at the onset of fasting,
gearing the fuel economy away from glucose uptake, conserving glucose for vital
functions, favouring fatty acid oxidation and triggering food-seeking behaviour.
The ghrelin system is a potential target for a range of pharmacological
interventions, but its pleiotropic nature makes selective treatments challenging.
PMID- 25111867
TI - The energy balance in cancer cachexia revisited.
AB - PURPOSE OF REVIEW: To review new putative mechanisms involved in the
pathophysiology of a disturbed energy balance in cancer cachexia, which can lead
to novel targets for clinical cachexia management. In the context of rapid
developments in tumour treatment with potential systemic consequences, this
article reviews recent data on energy requirements. Furthermore, we focus on new
insights in brown adipose tissue (BAT) activity and reward processing in the
brain in relation to the cachexia process. RECENT FINDINGS: Nearly no new data
have been published on energy requirements of cancer patients in the light of
comprehensive new therapies in oncology. New developments, such as the
introduction of staging with 18F-fluorodeoxyglucose PET-computed tomography
scanning, led to the observation that BAT activation may contribute to impaired
energy balance in cancer cachexia. Animal and human data to date provide an
indication that BAT activation indeed occurs, but its quantitative impact on the
degree of cachexia is controversial. The peripheral and central nervous system is
known to influence satiation, with a possible role for impaired food reward
processing in the brain. To date, there are limited confirmatory data, but this
is an interesting new area to explore for better understanding and treating
cancer-induced anorexia. SUMMARY: The multimodal approach to counteract cancer
cachexia should expand its targets to BAT and food reward processing in the
brain.
PMID- 25111868
TI - Integration of genome-wide of Stat3 binding and epigenetic modification mapping
with transcriptome reveals novel Stat3 target genes in glioma cells.
AB - BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is
constitutively activated in many human tumors, including gliomas, and regulates
the expression of genes implicated in proliferation, survival, apoptosis,
angiogenesis and immune regulation. Only a small fraction of those genes has been
proven to be direct STAT3 targets. In gliomas, STAT3 can play tumor suppressive
or oncogenic roles depending on the tumor genetic background with target genes
being largely unknown. RESULTS: We used chromatin immunoprecipitation, promoter
microarrays and deep sequencing to assess the genome-wide occupancy of phospho
(p)-Stat3 and epigenetic modifications of H3K4me3 and H3ac in C6 glioma cells.
This combined assessment identified a list of 1200 genes whose promoters have
both Stat3 binding sites and epigenetic marks characteristic for actively
transcribed genes. The Stat3 and histone markings data were also intersected with
a set of microarray data from C6 glioma cells after inhibition of Jak2/Stat3
signaling. Subsequently, we found 284 genes characterized by p-Stat3 occupancy,
activating histone marks and transcriptional changes. Novel genes were screened
for their potential involvement in oncogenesis, and the most interesting hits
were verified by ChIP-PCR and STAT3 knockdown in human glioma cells. CONCLUSIONS:
Non-random association between silent genes, histone marks and p-Stat3 binding
near transcription start sites was observed, consistent with its repressive role
in transcriptional regulation of target genes in glioma cells with specific
genetic background.
PMID- 25111869
TI - Breaking away from the norm: a new perspective on cancer therapeutics.
PMID- 25111870
TI - Formal [3+3] cycloaddition of indol-2-yl carbinol with azadiene and the oxidative
ring expansion reaction for the synthesis of indole azepinones.
AB - We present the unprecedented reaction of a [3+3] cyclization of indol-2-yl
carbinol with azadiene for the construction of a six-membered ring and the
subsequent oxidative ring expansion reaction for the construction of indole
azepinones.
PMID- 25111871
TI - Improved hydrogen production in the microbial electrolysis cell by inhibiting
methanogenesis using ultraviolet irradiation.
AB - Methanogenesis inhibition is essential for the improvement of hydrogen (H2) yield
and energy recovery in the microbial electrolysis cell (MEC). In this study,
ultraviolet (UV) irradiation was proposed as an efficient method for
methanogenesis control in a single chamber MEC. With 30 cycles of operation with
UV irradiation in the MEC, high H2 concentrations (>91%) were maintained, while
without UV irradiation, CH4 concentrations increased significantly and reached up
to 94%. In the MEC, H2 yields ranged from 2.87 +/- 0.03 to 3.70 +/- 0.11 mol
H2/mol acetate with UV irradiation and from 3.78 +/- 0.12 to 0.03 +/- 0.004 mol
H2/mol acetate without UV irradiation. Average energy efficiencies from the UV
irradiated MEC were 1.5 times of those without UV irradiation. Energy production
from the MEC without UV irradiation was a negative energy yield process because
of large amount of CH4 produced over time, which was mainly attributable to
cathodic hydrogenotrophic methanogenesis. Our results clearly showed that UV
irradiation could effectively inhibit methanogenesis and improve MEC performance
to produce H2.
PMID- 25111872
TI - Rhodium-catalyzed [(3+2)+1] carbocyclization reactions of
alkynylidenecyclopropanes with carbon monoxide: regiospecific construction of
polysubstituted phenols.
AB - The development of the rhodium-catalyzed [(3+2)+1] carbocyclization reaction of
alkynylidenecyclopropanes with carbon monoxide to construct polysubstituted
phenols is described. This work offers a convenient method for the selective
formation of tetra- and pentasubstituted phenols, which provide important
intermediates for target directed synthesis. Finally, the ability to
regiospecifically functionalize the phenols using conventional methods further
illustrates the utility of this process.
PMID- 25111873
TI - Is Gadolinium contrast enhancement necessary in screening MRI for asymmetric
sensorineural hearing loss?
PMID- 25111874
TI - The longer you stay, the worse your health? A critical review of the negative
acculturation theory among Asian immigrants.
AB - Researchers have become increasingly interested in the health patterns of
immigrants with longer residence in the United States, as this reveals the health
consequences of integration processes. The negative acculturation effect has been
the dominant interpretation of duration patterns, despite empirical and
theoretical uncertainties about this assumption. This theory assumes that
immigrant health declines with longer residence in the United States because of
poorer health behaviors and health risks that reflect Americanized lifestyles.
This paper reviews the empirical support for the negative acculturation theory
among Asian immigrants to determine if and when it is an appropriate
interpretation for duration patterns. I conclude that empirical inconsistencies
and methodological issues limit the negative acculturation theory as the primary
interpretation for duration patterns. First, there is no consistent evidence that
health behaviors decline with time. There is also substantial group heterogeneity
in duration patterns as well as heterogeneity across health outcomes. The
literature has not adequately addressed methodological shortcomings, such as
confounding by cohort effects or non-linear duration patterns. Length of
residence in the United States is still an important aspect of Asian immigrant
health, but the mechanisms of this relationship are still understudied. I propose
alternative frameworks between duration and health that consider environmental
influences and end with future research directions to explore research gaps.
PMID- 25111875
TI - Factors associated with no dental treatment in preschoolers with toothache: a
cross-sectional study in outpatient public emergency services.
AB - Many parents rely on emergency services to deal with their children's dental
problems, mostly pain and infection associated with dental caries. This cross
sectional study analyzed the factors associated with not doing an oral procedure
in preschoolers with toothache attending public dental emergency services. Data
were obtained from the clinical files of preschoolers treated at all nine dental
emergency centers in Goiania, Brazil, in 2011. Data were children's age and sex,
involved teeth, oral procedures, radiography request, medications prescribed and
referrals. A total of 531 files of children under 6 years old with toothache out
of 1,108 examined were selected. Children's mean age was 4.1 (SD 1.0) years
(range 1-5 years) and 51.6% were girls. No oral procedures were performed in
49.2% of cases; in the other 50.8%, most of the oral procedures reported were
endodontic intervention and temporary restorations. Primary molars were involved
in 48.4% of cases. With the exception of "sex", the independent variables tested
in the regression analysis significantly associated with non-performance of oral
procedures: age (OR 0.7; 95% CI 0.5-0.8), radiography request (OR 3.8; 95% CI 1.7
8.2), medication prescribed (OR 7.5; 95% CI 4.9-11.5) and patient referred to
another service (OR 5.7; 3.0-10.9). Many children with toothache received no oral
procedure for pain relief.
PMID- 25111876
TI - Study of epigenetic properties of Poly(HexaMethylene Biguanide) hydrochloride
(PHMB).
AB - Poly(HexaMethylene Biguanide) hydrochloride (PHMB) CAS No. [32289-58-0] is a
particularly effective member of the biguanides antiseptic chemical group, and
has been in use since the early fifties in numerous applications. It has been
proposed that PHMB be classified as a category 3 carcinogen although PHMB is not
genotoxic. It has been hypothesized that PHMB may have epigenetic properties
effects, including non-genotoxic modifications of DNA bases, DNA methylation and
mitogenic cytokine production. These properties have been assessed in vitro using
3 cell types: Caco-2 cells (from a human colon adenocarcinoma) with a non
functional p53 gene. (?p53: mut p53), N2-A (Neuro-2A cells, mouse neural cells),
the brain being a possible target organ in rodents and HepG2 cells (human
hepatocellular carcinoma) with functional p53 gene. From the concentration 1
ug/mL up to 20 ug/mL of PHMB, no effect was observed, either growth stimulation
or inhibition. Viability testing using neutral red led to an IC 50 of 20-25 ug/mL
after treatment with PHMB for 3 h, whereas the MTT test led to IC50 values of 80
ug/mL, 160 ug/mL and 160 ug/mL respectively for HepG2 cells, Neuro-2A cells and
Caco-2 cells. PHMB does not induce significant oxidative stress (production of
MDA or lipoperoxidation, nor does it induce hydroxylation of DNA (8-OH-dG) and/or
its hypermethylation (m5dC), the latter being strongly implicated in DNA
replication and regulation and cell division. PHMB does not induce significant
production of mitogenic cytokines such as TNF-alpha (tumor necrosis factor),
interleukins (IL-1 alpha), and the transcription factor nuclear factor kappa B
(NF-kappaB) which can cause either apoptosis or stimulate the growth of
transformed cells or tumors. Instead, from concentrations of 20 to 100 ug/mL,
PHMB kills cells of all types in less than 3 h. The expression of genes involved
in the mechanisms of cell death induced by PHMB, including p53, the pro apoptotic
gene bax and others, the anti-apoptotic bcl-2 and caspase-3 has been evaluated by
RT-PCR. Finally, the status of GAP-junctions (GJIC) in the presence of PHMB has
been determined and appeared to not be significantly affected. Taken together the
data show that in vitro PHMB does not exhibit clear and remarkable epigenetic
properties except a slight increase of some cytokines and transcription factor at
higher concentrations at which cell lysis occurs rapidly.
PMID- 25111877
TI - Physical activity and the perceived neighbourhood environment - looking at the
association the other way around.
AB - The association between physical activity (PA) and variables of the perceived
environment mainly originate from cross-sectional studies that introduced the
idea that the environment influences the PA level of residents. However, the
direction of cause and effect has not been solved with finality. The aim of this
study was to investigate whether residents' perception of their proximate
environment differs depending on their level of PA in transport and recreation.
We conducted a cross-sectional survey with residents of six different parts of
the city of Cologne, Germany. The sample of 470 adults (52.8% females; mean age =
35.5 +/- 13.8 years) filled in the Global Physical Activity Questionnaire (GPAQ),
as well as the European Environmental Questionnaire ALPHA. To distinguish between
residents with "low" and "high" PA, we split the samples into two on the basis of
the specific median in transport- and recreation-related PA. In the "high" vs.
"low" PA group of the overall sample, we noted 4%-16% more "PA favourable"
environmental perceptions in seven of the 15 environmental variables. Multiple
linear regression analyses were performed to investigate associations of socio
demographic correlates and transport- and recreation-related PA on the dependent
variables of the environmental perception. In this case, levels of PA were
significant predictors for eight of the 15 items concerning environmental
perceptions. Thus, the present study introduces the idea that residents with
higher levels of transport and recreational PA may perceive their environment in
a more "PA-favourable" way than residents with lower levels.
PMID- 25111878
TI - Atopic diseases and systemic lupus erythematosus: an epidemiological study of the
risks and correlations.
AB - Both atopic diseases and systemic lupus erythematosus (SLE) are immune disorders
that may lead to physical complications or multi-system comorbidities. This
population-based case-control study was designed to evaluate the risk of SLE
associated with atopic diseases. Using a national insurance claims dataset in
Taiwan, we identified 1673 patients newly diagnosed with SLE and 6692 randomly
selected controls frequency matched for gender, age and index date. The odds
ratios (OR) for SLE were calculated for associations with allergic rhinitis,
allergic conjunctivitis, atopic dermatitis and asthma. The SLE patients were
predominantly female (82.5%) with a mean age of 40.1 (SD = 18.2). The patients
with SLE had a higher rate of atopic dermatitis (6.81% vs. 3.06%), and asthma
(10.6% vs. 7.64%) was approximately 2 times more common in the patients with
lupus than in those without. The patients with atopic disease (atopic dermatitis,
allergic rhinitis, allergic conjunctivitis and asthma) were at a significant risk
for SLE. The overall risk for SLE increased as the number of atopic diseases
increased from 1.46 to 2.29, compared with-individuals without the diseases (p <
0.0001). In conclusion, this population-based case-control study demonstrates a
significant relationship between atopic diseases and the risk of SLE, especially
for females. Atopic dermatitis plays a stronger role than other types of atopic
disease in association with SLE.
PMID- 25111879
TI - In-vitro indicators of natural resistance and milk-producing ability in dairy
buffaloes (Bubalus bubalis).
AB - The aim of this study was to explore the possibility of detecting novel
phenotypes of natural resistance at the molecular level through the in-vitro
stimulation of monocyte-derived macrophages (MDMs). This study was conducted with
16 healthy buffaloes who were reared for milk production and for whom data on
milk-producing ability were available for several lactations. MDMs from
circulating monocytes were activated with interferon-gamma and
lipopolysaccharide. The response was evaluated using Western blotting to detect
the presence of 2 types of proteins separated by electrophoresis: tyrosine
phosphorylated proteins, which are indicators of the dynamic control of
biochemical pathways, and IkB-alpha (Kappa light polipeptide gene enhancer in B
cells Inhibitor, alpha) protein, which controls the activity of nuclear factor
kappa-light-chain-enhancer of activated B cells-a transcription factor that is
responsible for the expression of proinflammatory cytokines. The results showed
that the buffaloes who were positive for IkB-alpha proteins had a significantly
higher milk-producing ability than the buffaloes who did not express IkB-alpha.
On the contrary, no significant difference was detected between the high and low
milk-producing buffaloes with regard to the presence of tyrosine-phosphorylated
proteins. This preliminary study indicated that it may be possible to identify
the more disease-resistant nonhuman animals on a molecular level. The results,
therefore, indicate that an intense selection toward the increase of milk yield
could impair natural disease resistance in future dairy buffalo generations.
PMID- 25111881
TI - Warm thanks: gratitude expression facilitates social affiliation in new
relationships via perceived warmth.
AB - Recent theorizing on the nature and function of gratitude (the find-remind-and
bind theory; Algoe, 2012) stipulates that expressing gratitude should serve to
alert previously unacquainted peers to the potential for a high-quality social
bond (i.e., a find function). Although the logic of this premise is supported by
extant research, it has not, as yet, been tested empirically. In the current
study, participants received a note from a previously unacquainted peer that
contained an expression of gratitude (or did not) with regard to prior benefits
provided by the participant. After providing ratings of the peer and ostensibly
completing the study, participants were given an opportunity to spontaneously
give their contact information to the peer, which served as a behavioral measure
of affiliation. In line with the proposed find function of gratitude expressions,
recipients of expressions of gratitude were more likely to extend the effort to
continue the relationship with the novel peer by providing that peer with a means
to contact them. This experiment also provided evidence that perceptions of
interpersonal warmth (e.g., friendliness, thoughtfulness) serve as the mechanism
via which gratitude expressions facilitate affiliation: insofar as gratitude
expressions signaled interpersonal warmth of the expresser, they prompted
investment in the burgeoning social bond. As such, these findings provide the
first empirical evidence regarding 1 of the 3 central premises of the find-remind
and-bind theory of gratitude (Algoe, 2012) in the context of novel relationships.
PMID- 25111882
TI - Naturally-occurring expressive suppression in daily life depletes executive
functioning.
AB - The depleting impact of experimentally manipulated expressive suppression (ES) on
cognition (especially executive functioning and related processes) has been well
established (Baumeister, 2002a). However, the impact of ES that occurs naturally
in the course of daily life has not been examined. Sixty two adults (M = 22.89
years old) completed questions about recent ES burden (over the past 2 weeks and
on the test day) and completed cognitive measures assessing executive
functioning, working memory, and speed of information processing. Individuals
with higher-than-usual burden of ES on the test day exhibited poorer executive
performance and those with high ES over the past 2 weeks exhibited poorer
processing speed above and beyond depression, suggesting that ES burden as it
occurs in the course of daily life is associated with compromised cognitive
performance.
PMID- 25111880
TI - Effect of bisphosphonate use on risk of postmenopausal breast cancer: results
from the randomized clinical trials of alendronate and zoledronic acid.
AB - IMPORTANCE: Studies have shown that bisphosphonates may have antitumor and
antimetastatic properties. Recently, observational studies have suggested a
possible protective effect of bisphosphonates on breast cancer, but the effect of
bisphosphonate use on risk of breast cancer has not been tested in randomized
trials. OBJECTIVE: To assess the relationship of postmenopausal breast cancer
incidence and bisphosphonate use using data from 2 randomized (1:1), double
blind, placebo-controlled trials. DESIGN, SETTING, AND PARTICIPANTS: The Fracture
Intervention Trial (FIT) randomly assigned 6459 women aged 55 to 81 years to
alendronate or placebo for a mean follow-up of 3.8 years. The Health Outcomes and
Reduced Incidence With Zoledronic Acid Once Yearly-Pivotal Fracture Trial
(HORIZON-PFT) randomly assigned 7765 women aged 65 to 89 years to annual
intravenous zoledronic acid or placebo for a mean follow-up of 2.8 years. Data
were collected at clinical centers in the United States (FIT and HORIZON-PFT) and
in Asia and the Pacific, Europe, North America, and South America (HORIZON-PFT).
Women, in either study, with recurrent breast cancer or who reported a history of
breast cancer were excluded from analyses. In each trial, a blinded review was
conducted of each cancer adverse event report to verify incident invasive breast
cancer cases. The primary analysis compared events in the active vs placebo group
using a log-rank test. INTERVENTION: Alendronate vs placebo (FIT) or zoledronic
acid vs placebo (HORIZON-PFT). MAIN OUTCOMES AND MEASURES: Hazard ratio for
incident breast cancer in the bisphosphonate treatment group compared to the
placebo group. RESULTS: There was no significant difference in the rate of breast
cancer in FIT: 1.5% (n = 46) in the placebo group and 1.8% (n = 57) in the
alendronate group (hazard ratio [HR], 1.24 [95% CI, 0.84-1.83]). In HORIZON-PFT,
there was also no significant difference: 0.8% (n = 29) in the placebo group and
0.9% (n = 33) in the zoledronic acid group (HR, 1.15 [95% CI, 0.70-1.89]). There
was also no significant difference when the data from FIT and HORIZON-PFT were
pooled (HR, 1.20 [95% CI, 0.89-1.63]). CONCLUSIONS AND RELEVANCE: These 2
randomized clinical trials do not support the findings from observational
research. Contrary to the results from observational studies, we found that 3 to
4 years of bisphosphonate treatment did not decrease the risk of invasive
postmenopausal breast cancer. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
NCT00049829 (HORIZON-PFT).
PMID- 25111883
TI - Dissecting the global variation of gene expression for the functional
interpretation of transcriptome data.
AB - To perform their biological functions, individual genes exhibit varying ranges of
expression levels. Thus, considering the intrinsic variability of gene expression
can improve geneset-based functional analyses which are typically used to
interpret transcriptome data. Through the extensive quantitative analysis of the
expressional variability of individual genes using large collections of
transcriptome and proteome data, we found the existence of the intrinsic
variability of gene expression at the transcriptional level. Interestingly, genes
under post-translational regulation were not sensitively regulated at the
transcriptional level. Because genes have intrinsically different levels of
regulation at the transcription and translation stages, the functional geneset
based interpretation of transcriptome data should only include genes that are
significantly varied at the transcriptional level. Thus, by removing genes with
low transcriptional variation from the DNA microarray data, we showed that
geneset enrichment analysis could provide improved resolution in prioritizing
target functional pathways in several different experimental datasets.
PMID- 25111884
TI - Role of post-operative radiation boost for soft tissue sarcomas with positive
margins following pre-operative radiation and surgery.
AB - BACKGROUND AND OBJECTIVES: The role of a radiation therapy (RT) boost for
positive margins following pre-operative RT and surgery in extremity soft tissue
sarcomas (STS) is unclear. We assessed the contribution of a boost to local
control (LC), disease-free survival (DFS), and overall survival (OS). METHODS: We
identified 67 patients treated from 1987 to 2011 with pre-operative RT and
surgery with positive margin(s). Select patients received a boost delivered as
peri-operative Iridium-192 brachytherapy (BRT), intra-operative electrons (IORT),
or post-operative external beam RT (EBRT). RESULTS: Ten patients received no RT
boost, 10 received a BRT or IORT boost, and 47 received an EBRT boost. Five-year
LC rates for no boost, BRT/IORT boost, and EBRT boost were 100%, 78%, and 71% (P
= 0.5). On multivariate analysis, there were no significant predictors for LC.
Variables associated with improved DFS rates were single positive margin (P =
0.007) and low tumor grade (P = 0.03). Tumor size <5 cm (P = 0.003), low grade (P
= 0.001), and boost (P = 0.02) were associated with longer survival. CONCLUSIONS:
We did not identify a LC advantage for an RT boost. Given the unidentified
selection factors for delivery of boost and its potential toxicities, its role in
this setting remains unproven.
PMID- 25111885
TI - Sensitive diagnosis of cutaneous leishmaniasis by lesion swab sampling coupled to
qPCR.
AB - Variation in clinical accuracy of molecular diagnostic methods for cutaneous
leishmaniasis (CL) is commonly observed depending on the sample source, the
method of DNA recovery and the molecular test. Few attempts have been made to
compare these variables. Two swab and aspirate samples from lesions of patients
with suspected CL (n = 105) were evaluated alongside standard diagnosis by
microscopic detection of amastigotes or culture of parasites from lesion
material. Three DNA extraction methods were compared: Qiagen on swab and aspirate
specimens, Isohelix on swabs and Boil/Spin of lesion aspirates. Recovery of
Leishmania DNA was evaluated for each sample type by real-time polymerase chain
reaction detection of parasitic 18S rDNA, and the diagnostic accuracy of the
molecular method determined. Swab sampling combined with Qiagen DNA extraction
was the most efficient recovery method for Leishmania DNA, and was the most
sensitive (98%; 95% CI: 91-100%) and specific (84%; 95% CI: 64-95%) approach.
Aspirated material was less sensitive at 80% (95% CI: 70-88%) and 61% (95% CI: 50
72%) when coupled to Qiagen or Boil-Spin DNA extraction, respectively. Swab
sampling of lesions was painless, simple to perform and coupled with standardized
DNA extraction enhances the feasibility of molecular diagnosis of CL.
PMID- 25111886
TI - Impact of long-term erythrocytapheresis on growth and peak height velocity of
children with sickle cell disease.
AB - BACKGROUND: Children with sickle cell disease (SCD) lag in weight and height and
have a delayed growth spurt compared to normal children. We studied the effect of
long-term erythrocytapheresis (LTE) on the growth of children with SCD and the
age at which they attained peak height velocity. PROCEDURE: A retrospective chart
review was performed recording weight, height, and body mass index (BMI)
measurements of 36 patients with SCD who received LTE every 3-5 weeks for an
average duration of 5 years. The z-scores for weight, height, and BMI of these
patients were compared with that of patients with SCD from the Cooperative Study
of Sickle Cell Disease (CSSCD) and a sub-set of 64 controls matched for age, sex,
and initial growth parameter z-scores at the start of LTE. RESULTS: The z-scores
for all parameters improved significantly for our patients on LTE compared to
match controls from CSSCD and the entire pediatric CSSCD cohort (P-value: <0.01).
Peak height velocity was achieved 2 months earlier for females (P-value: 0.94)
and 11 months earlier for males (P-value: 0.02), who started LTE before 14 years
of age, compared to matched CSSCD controls. The study subjects who had not been
on regular simple transfusions prior to starting LTE had a mean serum ferritin of
681 ng/ml after LTE for an average duration of 63 months. CONCLUSION: LTE
improves the growth of children with SCD without the risk of iron overload.
PMID- 25111890
TI - Replica exchange Monte Carlo simulation of human serum albumin-catechin
complexes.
AB - Replica exchange Monte Carlo simulation equipped with an orientation-enhanced
hydrophobic interaction was utilized to study the impacts of molar ratio and
ionic strength on the complex formation of human serum albumin (HSA) and
catechin. Only a small amount of catechins was found to act as bridges in the
formation of HSA-catechin complexes. Selective binding behavior was observed at
low catechin to HSA molar ratio (R). Increase of catechin amount can suppress HSA
self-aggregation and diminish the selectivity of protein binding sites. Strong
saturation binding with short-range interactions was found to level off at around
4.6 catechins per HSA on average, while this number slowly increased with R when
long-range interactions were taken into account. Meanwhile, among the three rings
of catechin, the 3,4-dihydroxyphenyl (B-ring) shows the strongest preference to
bind HSA. Neither the aggregation nor the binding sites of the HSA-catechin
complex was sensitive to ionic strength, suggesting that the electrostatic
interaction is not a dominant force in such complexes. These results provide a
further molecular level understanding of protein-polyphenol binding, and the
strategy employed in this work shows a way to bridge phase behaviors at
macroscale and the distribution of binding sites at residue level.
PMID- 25111887
TI - Glycyrrhizin protects brain against ischemia-reperfusion injury in mice through
HMGB1-TLR4-IL-17A signaling pathway.
AB - High mobility group box 1 (HMGB1)-Toll-like receptor 4 (TLR4) signaling has been
recently found to induce interleukin (IL)-17A secretion in drug-induced hepatitis
and myocardial I/R injury. The purpose of this study is to evaluate whether HMGB1
TLR4 signaling could induce IL-17A secretion and lead to brain I/R injury. We
also sought to investigate whether glycyrrhizin elucidated its neuroprotective
effects through HMGB1-TLR4-IL-17A signaling pathway. Various biochemical
estimations, neurological status, and assessment of cerebral infarct size were
carried out 72h after middle cerebral artery occlusion (MCAO) stroke. Apoptotic
cells were assessed using a terminal deoxynucleotidyl transferase, dUTP nick and
labeling (TUNEL) kit. The expression of HMGB1, IL-17A, bcl-2, bax and cleaved
caspase-3, were determined by Western blot assay. In the present study we found
that glycyrrhizin significantly decreased HMGB1 protein expression. Glycyrrhizin
markedly reduced whereas recombinant HMGB1 (rHMGB1) increased IL-17A expression.
HMGB1 induced increase of IL-17A was significantly diminished in TLR4-mutant
C3H/HeJ mice. Brain injury and neurological deficits were largely abrogated by
glycyrrhizin or IL-17A knockout. In contrast, rHMGB1 or recombinant mouse IL-17A
markedly increased I/R injury. However, rHMGB1 had no effects on infarct size and
neurological deficits in Il17a(-/-) mice following brain I/R injury. In addition,
IL-17A knockout mice significantly increased bcl-2 protein expression and had
fewer apoptotic cells, whereas recombinant IL-17A-treated mice significantly
increased bax and cleaved caspase-3 protein expression and had more apoptotic
cells. Together these results indicate that glycyrrhizin has neuroprotective
efficacy in the postischemic brain through HMGB1-TLR4-IL-17A signaling pathway.
PMID- 25111891
TI - Poor outcome and death among youth, young adults, and midlife adults with eating
disorders: an investigation of risk factors by age at assessment.
AB - OBJECTIVE: Eating disorders (EDs) present across a broad age range, yet little is
known about the characteristics and outcome of midlife patients compared to
younger patients. Among patients seeking ED treatment who were stratified by age
at initial assessment (IA), this study aimed to (1) discern sociodemographic and
clinical differences, (2) determine outcome rates, and (3) identify predictors of
poor outcome including death. METHOD: Participants [219 females (12 years or
older, 94.1% Caucasian) who completed outcome assessment and 31 known decedents]
were stratified by age at IA (<18 as youth, 18-39 as young adult, and >=40 years
as midlife adult). Analyses of variance and chi-square tests identified group
differences; ordered logistic regression with stepwise selection identified
factors predicting outcome. RESULTS: Midlife adults were more significantly
compromised at follow-up compared to youths and young adults, including
psychological and physical quality of life, ineffectiveness, interpersonal
concerns, and general psychological maladjustment. Midlife adults had the highest
rates of poor outcome or death; good outcome was achieved by only 5.9% of midlife
adult compared to 14.0% of young adult and 27.5% of youth patients. Older age at
IA, alcohol and/or drug misuse, endocrine concerns, and absence of family ED
history predicted poor outcome or death. DISCUSSION: Midlife adults seeking ED
treatment have more complex medical and psychological concerns and poorer
outcomes than youths and young adults; further exploration is needed to improve
treatment outcome. Specialized treatment focusing on quality of life, comorbid
medical concerns, interpersonal connection, and emotion regulation is encouraged.
PMID- 25111892
TI - Designed synthesis of a highly conjugated hexaethynylbenzene-based host for
supramolecular architectures.
AB - The construction of efficient synthetic functional receptors with tunable
cavities, and the self-organization of guest molecules within these cavities
through noncovalent interactions can be challenging. Here we have prepared a
double-cavity molecular cup based on hexaethynylbenzene that possesses a highly
pi-conjugated interior for the binding of electron-rich guests. X-ray
crystallography, NMR spectroscopy, UV/Vis spectroscopy, fluorescent spectroscopy,
cyclic voltammetry, and SEM were used to investigate the structures and the
binding behaviors. The results indicated that the binding of a guest in one
cavity would affect the binding of the same or another guest in the other cavity.
The effect of electron transfer in this system suggests ample opportunities for
tuning the optical and electronic properties of the molecular cup and the
encapsulated guest. The encapsulation of different guests would also lead to
different aggregate nanostructures, which is a new way to tune their
supramolecular architectures.
PMID- 25111893
TI - Introducing diagnosis-related groups: is the information system ready?
AB - Diagnosis-related group (DRG) system is a classification system widely used in
health managements, the foundation of which lies in the medical information
system. A large effort had been made to improve the quality of discharge data
before the introduction of DRGs in Beijing. We extract discharge data from 108
local hospitals spanning 4 years before and after standardization to evaluate the
impact of standardization on DRG grouping performance. The data was grouped on an
annual basis in accordance with Beijing's local DRG system. Proportion of
ungrouped data, coefficient of variation (CV) and reduction in variance (RIV)
were used to measure the performance of the DRG system. Both the descriptive and
regression analysis indicate a significant reduction in terms of ungrouped data
and CV for expenditure, increase of RIV for expenditure and length of stay.
However, when there was no intervention, that is, between 2005 and 2006 and
between 2008 and 2009, changes in these indicators were all insignificant.
Therefore, the standardization of discharge data did improve data quality and
consequently enhanced the performance of DRGs. Developing countries with a
relatively weak information infrastructure should strengthen their medical
information system before the introduction of the DRG system.
PMID- 25111894
TI - Erythematous-to-brownish plaques on the upper back: a quiz. Phenytoin-induced T
cell predominant pseudolymphoma ("pseudomycosis fungoides") with T-cell
clonality.
PMID- 25111896
TI - Cell death induced by 2-phenylethynesulfonamide uncovers a pro-survival function
of BAX.
AB - PES (2-phenylethynesulfonamide) was initially identified as an inhibitor of p53
translocation to mitochondria and named Pifithrin-u. Further studies showed that
PES selectively killed tumour cells and was thus a promising anticancer agent.
PES-induced cell death was characterised by a non-apoptotic, autophagosome-rich
phenotype. We observed this phenotype via electron microscopy in wild type (wt)
and double Bax-/- Bak-/- (DKO) mouse embryonic fibroblasts (MEFs) treated with
PES. We excluded the involvement of effector caspases, BAX and BAK, in causing
PES-triggered cell death. Therefore, apoptosis was ruled out as the lethal mode
of action of PES. Surprisingly, MEFs containing BAX were significantly protected
from PES treatments. BAX overexpression in Bax-/- MEFs confirmed this pro
survival effect. Moreover, this protective effect required the ability of BAX to
localise to mitochondrial membranes. Conversely, mitochondrial fusion induced by
treatment with Mdivi-1 conferred increased resistance to MEFs subjected to PES
treatment. The involvement of BAX in the regulation of mitochondrial dynamics has
been reported. We propose the promotion of mitochondrial fusion by BAX to be the
pro-survival function attributed to BAX.
PMID- 25111895
TI - The use of valproic acid and multiple sclerosis.
AB - BACKGROUND: Animal studies have suggested that drugs inhibiting the enzyme
histone deacetylase might have a beneficial effect on multiple sclerosis (MS).
Valproic acid (VPA), an anti-epileptic drug, is the only widely used human drug
with a histone deacetylase inhibitory effect. OBJECTIVE: The objective of this
paper is to examine if VPA use is associated with a reduced risk of MS. METHODS:
We conducted a propensity score-matched cohort study in the period 1997-2011
linking nationwide register data on filled VPA prescriptions, MS cases, and
several covariates. The VPA users were matched on propensity scores in a 1:4
ratio with non-users of VPA. Incidence rates of MS were compared among VPA users
and non-users of VPA using Cox regression to estimate hazard ratios (HRs).
RESULTS: Among 16 028 ever-users of VPA and 54 172 non-users, 18 and 26 cases of
MS were identified, respectively. Neither current VPA users nor recent users of
VPA, who had ceased VPA treatment within the last year, were at a reduced risk of
MS compared with non-users of VPA (HR = 1.30 (95% confidence interval, 0.44
3.80), n = 4, and HR = 1.22 (0.28-5.32), n = 2, respectively). Similarly, in an
intention-to-treat analysis, ever-users of VPA were not at reduced risk of MS (HR
= 2.41 (1.32-4.43), n = 18). CONCLUSION: In the first human study addressing a
possible beneficial effect of VPA use on the risk of MS, we found no support for
a protective effect. However, given the wide confidence intervals, only large
effects can be ruled out with sufficient certainty.
PMID- 25111897
TI - HDAC6 sustains growth stimulation by prolonging the activation of EGF receptor
through the inhibition of rabaptin-5-mediated early endosome fusion in gastric
cancer.
AB - The aberrant regulation of histone deacetylase 6 (HDAC6) contributes to malignant
progression in various types of cancer, but the mechanism underlying gastric
carcinogenesis remains unknown. Aberrant HDAC6 overexpression was observed in a
subset of human gastric cancer cells. HDAC6 knockdown caused the significant
inhibition of gastric cancer cell growth without affecting the transition of cell
cycles or the processing of cell death. We demonstrate that an increase in
epidermal growth factor receptor (EGFR) signaling through decreased EGFR
degradation was mediated by HDAC6 in gastric carcinogenesis. These results
establish a molecular mechanism responsible for oncogenic HDAC6, explaining how
EGFR signaling induced by the growth factor is sustained during the malignant
progression of gastric cancer.
PMID- 25111898
TI - Gain-of-function of mutant p53: mutant p53 enhances cancer progression by
inhibiting KLF17 expression in invasive breast carcinoma cells.
AB - Kruppel-like-factor 17 (KLF17) is a negative regulator of metastasis and
epithelial-mesenchymal-transition (EMT). However, its expression is downregulated
in metastatic breast cancer that contains p53 mutations. Here, we show that
mutant-p53 plays a key role to suppress KLF17 and thereby enhances cancer
progression, which defines novel gain-of-function (GOF) of mutant-p53. Mutant-p53
interacts with KLF17 and antagonizes KLF17 mediated EMT genes transcription.
Depletion of KLF17 promotes cell viability, decreases apoptosis and induces drug
resistance in metastatic breast cancer cells. KLF17 suppresses cell migration and
invasion by decreasing CD44, PAI-1 and Cyclin-D1 expressions. Taken together, our
results show that KLF17 is important for the suppression of metastasis and could
be a potential therapeutic target during chemotherapy.
PMID- 25111900
TI - Streaming potential near a rotating porous disk.
AB - Theory and experimental results for the streaming potential measured in the
vicinity of a rotating porous disk-shaped sample are described. Rotation of the
sample on its axis draws liquid into its face and casts it from the periphery.
Advection within the sample engenders streaming current and streaming potential
that are proportional to the zeta potential and the disk's major dimensions. When
Darcy's law applies, the streaming potential is proportional to the square of the
rotation at low rate but becomes invariant with rotation at high rate. The
streaming potential is invariant with the sample's permeability at low rate and
is proportional to the inverse square of the permeability at high rate. These
predictions were tested by determining the zeta potential and permeability of the
loop side of Velcro, a sample otherwise difficult to characterize; reasonable
values of -56 mV for zeta and 8.7 * 10(-9) m(2) for the permeability were
obtained. This approach offers the ability to determine both the zeta potential
and the permeability of materials having open structures. Compressing them into a
porous plug is unnecessary. As part of the development of the theory, a
convenient formula for a flow-weighted volume-averaged space-charge density of
the porous medium, -epsilonzeta/k, was obtained, where epsilon is the
permittivity, zeta is the zeta potential, and k is the Darcy permeability. The
formula is correct when Smoluchowski's equation and Darcy's law are both valid.
PMID- 25111901
TI - Pulsed transfer etching of PS-PDMS block copolymers self-assembled in 193 nm
lithography stacks.
AB - This work presents the graphoepitaxy of high-chi block copolymers (BCP) in
standard industry-like lithography stacks and their transfer into the silicon
substrate The process includes conventional 193 nm photolithography, directed
self-assembly of polystyrene-block-polydimethylsiloxane (PS-b-PDMS) and pulsed
plasma etching to transfer the obtained features into the substrate. PS-b-PDMS
has a high Flory-Huggins interaction parameter (high-chi) and is capable of
achieving sub-10 nm feature sizes. The photolithography stack is fabricated on
300 mm diameter silicon wafers and is composed of three layers: spin-on-carbon
(SoC), silicon-containing anti-reflective coating (SiARC) and 193 nm
photolithography resist. Sixty-nanometer-deep trenches are first patterned by
plasma etching in the SiARC/SoC stack using the resist mask. The PS-b-PDMS is
then spread on the substrate surface. Directed self-assembly (DSA) of the BCP is
induced by a solvent vapor annealing process and PDMS cylinders parallel to the
substrate surface are obtained. The surface chemistry based on SoC permits an
efficient etching process into the underlying silicon substrate. The etching
process is performed under dedicated pulsed plasma etching conditions. Fifteen
nanometer half-pitch dense line/space features are obtained with a height up to
90 nm.
PMID- 25111902
TI - Spectral entropy, ecological resilience, and adaptive capacity for understanding,
evaluating, and managing ecosystem stability and change.
PMID- 25111903
TI - Synthesis of polymeric phosphonates for selective delivery of radionuclides to
osteosarcoma.
AB - Discussed in detail is the synthesis and primary structure characterization of
two polymers aimed at advancing the treatment of pediatric osteosarcoma. These
polymers are designed to systemically deliver radiometals specifically to
osteosarcomas using the passive targeting mechanism of enhanced permeability and
retention (the EPR effect). The approach begins with the synthesis of a polymer
capable of binding radiometals, for which prior data show improved site-specific
targeting of solid tumors. Building on this success, a second polymer has been
designed for improving the efficacy of currently available radionuclide therapies
by incorporating the FDA-approved small-molecule ligand Quadramet directly onto
the polymer structure. Time-activity curves of the phosphonate-functionalized
polymers show rapid clearance from the central compartment and nontargeted
organs, with up to 65% of injected activity being excreted within 3 hours. Both
polymer ligands demonstrate good osteosarcoma targeting capability with little to
no uptake in organs associated with the dose-limiting bone marrow. Additionally,
biodistribution studies in nonosseous tumor models demonstrate the tumor
targeting mechanism of the polymer ligands, which appears to be influenced by the
high affinity of the phosphonate functionality for the positively charged
hydroxyapatite mineral found in bone tumors.
PMID- 25111904
TI - Preparation and electric property of polysilsesquioxane thin films incorporating
carbazole groups.
AB - New silsesquioxane incorporating a carbazole groups (PCTSQ) has been synthesized
by a click thiol-ene reaction and a subsequent sol-gel reaction. To evaluate the
electric property of this hybrid, diode devices have been fabricated by using
PCTSQ thin film by spin-coating onto n-type ZnO film prepared by the
electrodeposition method. The thin film hybrid devices showed good electric
characteristics and high rectification ratio, as well as worked as a rectifier.
PMID- 25111905
TI - Protection from pulmonary tissue damage associated with infection of cynomolgus
macaques by highly pathogenic avian influenza virus (H5N1) by low dose natural
human IFN-alpha administered to the buccal mucosa.
AB - Using an established nonhuman primate model for H5N1 highly pathogenic influenza
virus infection in humans, we have been able to demonstrate the prophylactic
mitigation of the pulmonary damage characteristic of human fatal cases from
primary influenza virus pneumonia with a low dose oral formulation of a
commercially available parenteral natural human interferon alpha (Alferon N
Injection(r)). At the highest oral dose (62.5IU/kg body weight) used there was a
marked reduction in the alveolar inflammatory response with minor evidence of
alveolar and interstitial edema in contrast to the hemorrhage and inflammatory
response observed in the alveoli of control animals. The mitigation of severe
damage to the lower pulmonary airway was observed without a parallel reduction in
viral titers. Clinical trial data will be necessary to establish its prophylactic
human efficacy for highly pathogenic influenza viruses.
PMID- 25111899
TI - A new model army: Emerging fish models to study the genomics of vertebrate Evo
Devo.
AB - Many fields of biology--including vertebrate Evo-Devo research--are facing an
explosion of genomic and transcriptomic sequence information and a multitude of
fish species are now swimming in this "genomic tsunami." Here, we first give an
overview of recent developments in sequencing fish genomes and transcriptomes
that identify properties of fish genomes requiring particular attention and
propose strategies to overcome common challenges in fish genomics. We suggest
that the generation of chromosome-level genome assemblies--for which we introduce
the term "chromonome"--should be a key component of genomic investigations in
fish because they enable large-scale conserved synteny analyses that inform
orthology detection, a process critical for connectivity of genomes. Orthology
calls in vertebrates, especially in teleost fish, are complicated by divergent
evolution of gene repertoires and functions following two rounds of genome
duplication in the ancestor of vertebrates and a third round at the base of
teleost fish. Second, using examples of spotted gar, basal teleosts, zebrafish
related cyprinids, cavefish, livebearers, icefish, and lobefin fish, we
illustrate how next generation sequencing technologies liberate emerging fish
systems from genomic ignorance and transform them into a new model army to answer
longstanding questions on the genomic and developmental basis of their
biodiversity. Finally, we discuss recent progress in the genetic toolbox for the
major fish models for functional analysis, zebrafish, and medaka, that can be
transferred to many other fish species to study in vivo the functional effect of
evolutionary genomic change as Evo-Devo research enters the postgenomic era.
PMID- 25111906
TI - Ellagitannins as synergists of ACV on the replication of ACV-resistant strains of
HSV 1 and 2.
AB - The plant-derived polyphenolic compounds castalagin, vescalagin and grandinin (C
glucosidic ellagitannins containing nonahydroxyterphenoyl) manifested a strong
inhibitory effect on the replication of acyclovir-resistant strains of herpes
simplex viruses (HSV) type 1 and 2 in MDBK cells in focus forming units (i.e.,
microscopically registered microplaques) reduction assay and in two variants of
cytopathic effect inhibition test. The effect on the acyclovir (ACV)-resistant
herpes simplex virus type 1 (HSV-1) strain was markedly higher compared to that
on the ACV-resistant herpes simplex virus type 2 (HSV-2). The three compounds
showed comparable levels of antiviral activity against ACV-resistant HSV strains,
in contrast with previous results where castalagin exerted the highest degree of
activity against wild type HSV strains (Vilhelmova et al., 2011). Combinations of
ellagitannins and ACV were tested on the ACV-resistant strains of both HSV-1 and
2 and produced synergistic effects that were revealed by applying the three
dimensional approach of Prichard and Shipman (1990). The ellagitannin(s)-ACV
combination applied against ACV-resistant HSV-1 produced a much stronger
synergistic effect compared to the effect observed against ACV-resistant HSV-2.
The study of the effects of the combination ellagitannin(s)-ACF on intact cell
monolayers did not show any toxicity resulting from interaction between the two
substances. Altogether, the results obtained in this study demonstrate the highly
promising potential of these plant polyphenols as antiherpetic agents.
PMID- 25111908
TI - Highly efficient hybrid solar cells with tunable dipole at the donor-acceptor
interface.
AB - Effects of molecular dipole at the conjugated polymer-nanocrystal interface on
the energy level alignment, the exciton dissociation process, and consequently
the photovoltaic performance of poly[2,6-(4,4-bis-(2-ethylhexyl)-4H
cyclopenta[2,1-b;3,4-b']-dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)]
(PCPDTBT):CdSe quantum dot bulk heterojunction hybrid solar cells are
systemically studied. Power conversion efficiency up to 4.0% is achieved when 4
fluorobenzenethiol is used for ligand exchange.
PMID- 25111907
TI - Improving rheology and enzymatic hydrolysis of high-solid corncob slurries by
adding lignosulfonate and long-chain fatty alcohols.
AB - The effects of lignosulfonate (SXSL) and long-chain fatty alcohols (LFAs) on the
rheology and enzymatic hydrolysis of high-solid corncob slurries were
investigated. The application of 2.5% (w/w) SXSL increased the substrate
enzymatic digestibility (SED) of high-solid corncob slurries at 72 h from 31.7 to
54.0%, but meanwhile it increased the slurry's yield stress and complex viscosity
to make the slurry difficult to stir and pump. The smallest molecular weight (MW)
SXSL fraction had the strongest enhancement on SED. The SXSL fraction with large
MW had a negative effect on rheology. n-Octanol (C8) and n-decanol (C10) improved
the rheological properties of high-solid slurry and are strong enough to
counteract the negative effect of SXSL. Furthermore, C8 and C10 clearly enhanced
the enzymatic hydrolysis of high-solid corncob slurries with and without SXSL. A
mechanism was proposed to explain the observed negative effect of SXSL and the
positive effect of LFAs on the rheological properties.
PMID- 25111909
TI - Stable single-molecule lines of terrylene in polycrystalline para-dichlorobenzene
at 1.5 K.
AB - The spectroscopic properties of single terrylene (Tr) molecules are studied in a
polycrystalline matrix of para-dichlorobenzene (p-DCB) at 1.5 K. Samples grown in
a glass capillary show a very strong site at 597 nm, which is redshifted by more
than 700 cm(-1) from the observed transition energy for Tr in p-DCB prepared as a
film on a coverslip (572 nm). Each of these two sites is characterized by
measuring their single-molecule spectroscopic parameters at 1.5 K. Lifetime
limited linewidths of 45+/-5 MHz are found for both sites. Fluorescence detection
rates reach 8*10(4) count s(-1) at saturation. The spectral trails of the
majority of single molecules show no spectral jumps, indicating an absence of
interacting two-level systems; however, the small distribution of linewidths may
indicate weak interactions with low-frequency modes. Frequency jumps are observed
for 10 % of the molecules. The complete emission spectra from two different
single molecules at the center of each of the two sites is presented. Debye
Waller factors of alphaDW=0.33+/-0.05 for the normal site (572 nm) and
alphaDW=0.30+/-0.05 for the red site (597 nm) are reported. This new host-guest
system provides a quick and easy way to obtain lifetime-limited single-molecule
lines.
PMID- 25111910
TI - Fragmentation of urinary calculi in vitro by burst wave lithotripsy.
AB - PURPOSE: We developed a new method of lithotripsy that uses short, broadly
focused bursts of ultrasound rather than shock waves to fragment stones. We
investigated the characteristics of stone comminution by burst wave lithotripsy
in vitro. MATERIALS AND METHODS: Artificial and natural stones (mean +/- SD size
8.2 +/- 3.0 mm, range 5 to 15) were treated with ultrasound bursts using a
focused transducer in a water bath. Stones were exposed to bursts with focal
pressure amplitude of 6.5 MPa or less at a 200 Hz burst repetition rate until
completely fragmented. Ultrasound frequencies of 170, 285 and 800 kHz were
applied using 3 transducers, respectively. Time to fragmentation for each stone
type was recorded and fragment size distribution was measured by sieving.
RESULTS: Stones exposed to ultrasound bursts were fragmented at focal pressure
amplitudes of 2.8 MPa or greater at 170 kHz. Fractures appeared along the stone
surface, resulting in fragments that separated at the surface nearest to the
transducer until the stone was disintegrated. All natural and artificial stones
were fragmented at the highest focal pressure of 6.5 MPa with a mean treatment
duration of 36 seconds for uric acid stones to 14.7 minutes for cystine stones.
At a frequency of 170 kHz the largest artificial stone fragments were less than 4
mm. Exposure at 285 and 800 kHz produced only fragments less than 2 mm and less
than 1 mm, respectively. CONCLUSIONS: Stone comminution with burst wave
lithotripsy is feasible as a potential noninvasive treatment method for
nephrolithiasis. Adjusting the fundamental ultrasound frequency allows for stone
fragment size to be controlled.
PMID- 25111912
TI - Early discontinuation of antibiotic prophylaxis in patients with persistent
primary vesicoureteral reflux initially detected during infancy: outcome analysis
and risk factors for febrile urinary tract infection.
AB - PURPOSE: We retrospectively assessed the incidence of and risk factors for
febrile urinary tract infection in children during active surveillance after
early discontinuation of antibiotic prophylaxis. MATERIALS AND METHODS: We
retrospectively evaluated 9 females and 61 uncircumcised males diagnosed with
primary vesicoureteral reflux before age 1 year who had persistent reflux on
followup voiding cystourethrogram and were subsequently followed under active
surveillance without continuous antibiotic prophylaxis. Patients with secondary
vesicoureteral reflux or associated urological abnormality were excluded.
Clinical outcomes, including incidence of febrile urinary tract infection and new
scar formation, were evaluated. Risk factors for febrile urinary tract infection
were also analyzed. RESULTS: Mean age at stopping continuous antibiotic
prophylaxis was 21 months, and mean followup was 61 months. During active
surveillance 21 patients had febrile urinary tract infection, and the 5-year
infection-free rate under active surveillance was 67.5%. One or 2 foci of minimal
new scarring developed in 4 of 16 patients who underwent followup dimercapto
succinic acid scan after febrile urinary tract infection. On multivariate
analysis dilated vesicoureteral reflux on followup voiding cystourethrogram was
the only significant risk factor for febrile urinary tract infection.
CONCLUSIONS: This study revealed that about two-thirds of patients with
persistent vesicoureteral reflux were free of febrile urinary tract infection
during 5 years of active surveillance. Those with dilated vesicoureteral reflux
on followup voiding cystourethrogram are at significantly greater risk for
febrile urinary tract infection. Accordingly active surveillance, especially in
patients with nondilated vesicoureteral reflux on followup voiding
cystourethrogram, seems to be a safe option even in children who have not yet
been toilet trained.
PMID- 25111911
TI - Fluoroquinolone resistance in the rectal carriage of men in an active
surveillance cohort: longitudinal analysis.
AB - PURPOSE: Rectal swabs can identify men with fluoroquinolone resistant bacteria
and decrease the infection rate after transrectal ultrasound guided prostate
biopsy by targeted antimicrobial prophylaxis. We evaluated the rate of
fluoroquinolone resistance in an active surveillance cohort with attention to
factors associated with resistance and changes in resistance with time. MATERIALS
AND METHODS: We evaluated 416 men with prostate cancer on active surveillance who
underwent rectal swabs to assess the rate of fluoroquinolone resistance compared
to that in men undergoing diagnostic transrectal ultrasound guided prostate
biopsy. The chi-square test and Student t-test were used to compare categorical
and continuous variables, respectively. Poisson regression analysis was used for
multivariate analysis. RESULTS: On the initial swab fluoroquinolone resistance
was found in 95 of 416 men (22.8%) on active surveillance compared to 54 of 221
(24.4%) in the diagnostic biopsy cohort (p = 0.675). Diabetes was found in 4.0%
of the fluoroquinolone sensitive group vs 14.7% of the resistant group (p
<0.001). Biopsy history was not associated with resistance. Of those with a
resistant first swab 62.9% had a resistant second swab and 88.9% of those with 2
resistant swabs showed resistance on the third swab. Of men with a sensitive
first swab 10.6% showed resistance on the second swab and 10.6% of those with 2
sensitive swabs had resistant third swabs. CONCLUSIONS: One of 4 men who present
for surveillance and diagnostic transrectal ultrasound guided prostate biopsy
have rectal flora resistant to fluoroquinolone. Resistance is significantly
associated with diabetes but the number of prior biopsies is not. Men with
fluoroquinolone resistant flora tend to remain resistant with time.
PMID- 25111913
TI - Histological analysis of the kidney tumor-parenchyma interface.
AB - PURPOSE: During enucleative partial nephrectomy excision is performed adjacent to
the tumor edge. To better determine the oncologic propriety of enucleative
partial nephrectomy we histologically examined the tumor-parenchyma interface.
MATERIALS AND METHODS: Archived hematoxylin and eosin stained slides of 124
nephrectomy specimens were rereviewed. We evaluated representative sections of
tumor abutting the renal parenchyma and overlying pseudocapsule/perirenal fat
were selected at 4 mm(2) sectors apportioned 1, 2, 3 and 4 mm, respectively, from
the tumor edge. RESULTS: Median tumor size was 3.5 cm. Of the tumors 111 were
malignant (90%) and 119 (96%) had a pseudocapsule with a median thickness of 0.6
mm. Of malignant and benign tumors 82% and 31%, respectively, had an intrarenal
pseudocapsule (p < 0.001). Pseudocapsule invasion was noted in 45% of cancers and
15% of benign tumors (p < 0.04). Of pT1a cancers 36% showed intrarenal
pseudocapsule invasion. No patient had positive surgical margins. Intrarenal
pseudocapsule invasion correlated with clear cell renal cell carcinoma histology
but not with cancer size, grade, necrosis or margin width. Inflammation,
nephrosclerosis, glomerulosclerosis and arteriosclerosis decreased with
increasing distance from the tumor edge. At 1 mm changes were moderate to severe
in 38%, 32%, 20% and 17% of tumors while at 5 mm changes were mild in 2.5%, 0.8%,
0.8% and 4%, respectively (p <0.001). Mean arteriolar diameter decreased with
tumor proximity (p < 0.0001). CONCLUSIONS: Most renal cancers have an intrarenal
pseudocapsule. Partial nephrectomy excision adjacent to the tumor edge appears to
be histologically safe. Because 18% of cancers lacked a discernible intrarenal
pseudocapsule and 25% of pT1a cancers showed intrarenal pseudocapsule invasion,
extreme care is needed to avoid positive margins during enucleative partial
nephrectomy.
PMID- 25111914
TI - Endometriosis, endocervicosis and mullerianosis of the bladder.
PMID- 25111915
TI - Data requirements for electronic surveillance of healthcare-associated
infections.
AB - Electronic surveillance for healthcare-associated infections (HAIs) is
increasingly widespread. This is driven by multiple factors: a greater burden on
hospitals to provide surveillance data to state and national agencies, financial
pressures to be more efficient with HAI surveillance, the desire for more
objective comparisons between healthcare facilities, and the increasing amount of
patient data available electronically. Optimal implementation of electronic
surveillance requires that specific information be available to the surveillance
systems. This white paper reviews different approaches to electronic
surveillance, discusses the specific data elements required for performing
surveillance, and considers important issues of data validation.
PMID- 25111917
TI - Antimicrobial stewardship strategies: preauthorization or postprescription audit
and feedback?
PMID- 25111916
TI - Comparison of prior authorization and prospective audit with feedback for
antimicrobial stewardship.
AB - OBJECTIVE: Although prior authorization and prospective audit with feedback are
both effective antimicrobial stewardship program (ASP) strategies, the relative
impact of these approaches remains unclear. We compared these core ASP strategies
at an academic medical center. DESIGN: Quasi-experimental study. METHODS: We
compared antimicrobial use during the 24 months before and after implementation
of an ASP strategy change. The ASP used prior authorization alone during the
preintervention period, June 2007 through May 2009. In June 2009, many
antimicrobials were unrestricted and prospective audit was implemented for
cefepime, piperacillin/tazobactam, and vancomycin, marking the start of the
postintervention period, July 2009 through June 2011. All adult inpatients who
received more than or equal to 1 dose of an antimicrobial were included. The
primary end point was antimicrobial consumption in days of therapy per 1,000
patient-days (DOT/1,000-PD). Secondary end points included length of stay (LOS).
RESULTS: In total, 55,336 patients were included (29,660 preintervention and
25,676 postintervention). During the preintervention period, both total systemic
antimicrobial use (-9.75 DOT/1,000-PD per month) and broad-spectrum anti-gram
negative antimicrobial use (-4.00 DOT/1,000-PD) declined. After the introduction
of prospective audit with feedback, however, both total antimicrobial use (+9.65
DOT/1,000-PD per month; P < .001) and broad-spectrum anti-gram-negative
antimicrobial use (+4.80 DOT/1,000-PD per month; P < .001) increased
significantly. Use of cefepime and piperacillin/tazobactam both significantly
increased after the intervention (P = .03). Hospital LOS and LOS after first
antimicrobial dose also significantly increased after the intervention (P = .016
and .004, respectively). CONCLUSIONS: Significant increases in antimicrobial
consumption and LOS were observed after the change in ASP strategy.
PMID- 25111918
TI - Development of an antibiotic spectrum score based on veterans affairs culture and
susceptibility data for the purpose of measuring antibiotic de-escalation: a
modified Delphi approach.
AB - OBJECTIVE: Development of a numerical score to measure the microbial spectrum of
antibiotic regimens (spectrum score) and method to identify antibiotic de
escalation events based on application of the score. DESIGN: Web-based modified
Delphi method. PARTICIPANTS: Physician and pharmacist antimicrobial stewards
practicing in the United States recruited through infectious diseases-focused
listservs. METHODS: Three Delphi rounds investigated: organisms and antibiotics
to include in the spectrum score, operationalization of rules for the score, and
de-escalation measurement. A 4-point ordinal scale was used to score antibiotic
susceptibility for organism-antibiotic domain pairs. Antibiotic regimen scores,
which represented combined activity of antibiotics in a regimen across all
organism domains, were used to compare antibiotic spectrum administered early
(day 2) and later (day 4) in therapy. Changes in spectrum score were calculated
and compared with Delphi participants' judgments on de-escalation with 20
antibiotic regimen vignettes and with non-Delphi steward judgments on de
escalation of 300 pneumonia regimen vignettes. Method sensitivity and specificity
to predict expert de-escalation status were calculated. RESULTS: Twenty-four
participants completed all Delphi rounds. Expert support for concepts utilized in
metric development was identified. For vignettes presented in the Delphi, the
sign of change in score correctly classified de-escalation in all vignettes
except those involving substitution of oral antibiotics. The sensitivity and
specificity of the method to identify de-escalation events as judged by non
Delphi stewards were 86.3% and 96.0%, respectively. CONCLUSIONS: Identification
of de-escalation events based on an algorithm that measures microbial spectrum of
antibiotic regimens generally agreed with steward judgments of de-escalation
status.
PMID- 25111919
TI - Multisite exploration of clinical decision making for antibiotic use by emergency
medicine providers using quantitative and qualitative methods.
AB - OBJECTIVES: To explore current practices and decision making regarding
antimicrobial prescribing among emergency department (ED) clinical providers.
METHODS: We conducted a survey of ED providers recruited from 8 sites in 3
cities. Using purposeful sampling, we then recruited 21 providers for in-depth
interviews. Additionally, we observed 10 patient-provider interactions at one of
the ED sites. SAS 9.3 was used for descriptive and predictive statistics.
Interviews were audio recorded, transcribed, and analyzed using a thematic,
constructivist approach with consensus coding using NVivo 10.0. Field and
interview notes collected during the observational study were aligned with themes
identified through individual interviews. RESULTS: Of 150 survey respondents, 76%
agreed or strongly agreed that antibiotics are overused in the ED, while half
believed they personally did not overprescribe. Eighty-nine percent used a
smartphone or tablet in the ED for antibiotic prescribing decisions. Several
significant differences were found between attending and resident physicians.
Interview analysis identified 42 codes aggregated into the following themes: (1)
resource and environmental factors that affect care; (2) access to and quality of
care received outside of the ED consult; (3) patient-provider relationships; (4)
clinical inertia; and (5) local knowledge generation. The observational study
revealed limited patient understanding of antibiotic use. Providers relied
heavily upon diagnostics and provided limited education to patients. Most
patients denied a priori expectations of being prescribed antibiotics.
CONCLUSIONS: Patient, provider, and healthcare system factors should be
considered when designing interventions to improve antimicrobial stewardship in
the ED setting.
PMID- 25111920
TI - Infection prevention practices in neonatal intensive care units reporting to the
national healthcare safety network.
AB - BACKGROUND: Patients in the neonatal intensive care unit (NICU) are at high risk
for healthcare-associated infections. Variability in reported infection rates
among NICUs exists, possibly related to differences in prevention strategies. A
better understanding of current prevention practices may help identify prevention
gaps and areas for further research. METHODS: We surveyed infection control staff
in NICUs reporting to the National Healthcare Safety Network (NHSN) to assess
strategies used to prevent methicillin-resistant Staphylococcus aureus (MRSA)
transmission and central line-associated bloodstream infections in NICUs.
RESULTS: Staff from 162 of 342 NICUs responded (response rate, 47.3%). Most
(92.3%) NICUs use central line insertion and maintenance bundles, but maintenance
practices varied, including agents used for antisepsis and frequency of dressing
changes. Forty-two percent reported routine screening for MRSA colonization upon
admission for all patients. Chlorhexidine gluconate (CHG) use for central line
care for at least 1 indication (central line insertion, dressing changes, or
port/cap antisepsis) was reported in 82 NICUs (51.3%). Among sixty-five NICUs
responding to questions on CHG use restrictions, 46.2% reported no restrictions.
CONCLUSIONS: Our survey illustrated heterogeneity of CLABSI and MRSA prevention
practices and underscores the need for further research to define optimal
strategies and evidence-based prevention recommendations for neonates.
PMID- 25111921
TI - The association of state legal mandates for data submission of central line
associated bloodstream infections in neonatal intensive care units with process
and outcome measures.
AB - OBJECTIVE: To determine the association between state legal mandates for data
submission of central line-associated bloodstream infections (CLABSIs) in
neonatal intensive care units (NICUs) with process and outcome measures. DESIGN:
Cross-sectional study. PARTICIPANTS: National sample of level II/III and III
NICUs participating in National Healthcare Safety Network (NHSN) surveillance.
METHODS: State mandates for data submission of CLABSIs in NICUs in place by 2011
were compiled and verified with state healthcare-associated infection
coordinators. A web-based survey of infection control departments in October 2011
assessed CLABSI prevention practices, ie, compliance with checklist/bundle
components (process measures) in ICUs including NICUs. Corresponding 2011 NHSN
NICU CLABSI rates (outcome measures) were used to calculate standardized
infection ratios (SIRs). Association between mandates and process and outcome
measures was assessed by multivariable logistic regression. RESULTS: Among 190
study NICUs, 107 (56.3%) were located in states with mandates, with mandates in
place >3 years in 52 (49%). More NICUs in states with mandates reported >=95%
compliance to at least 1 CLABSI prevention practice (52.3%-66.4%) than NICUs in
states without mandates (28.9%-48.2%). Mandates were predictors of >=95%
compliance with all practices (odds ratio, 2.8; 95% confidence interval, 1.4
6.1). NICUs in states with mandates reported lower mean CLABSI rates in the <=750
g birth weight group (2.4 vs 5.7 CLABSIs/1,000 central line-days) but not in
others. Mandates were not associated with SIR <1. CONCLUSIONS: State mandates for
NICU CLABSI data submission were significantly associated with >=95% compliance
with CLABSI prevention practices, which declined with the duration of mandate but
not with lower CLABSI rates.
PMID- 25111922
TI - The effect of multiple concurrent central venous catheters on central line
associated bloodstream infections.
AB - OBJECTIVE: The current central line-associated bloodstream infection (CLABSI)
surveillance rate calculation does not account for multiple concurrent central
venous catheters (CVCs). The presence of multiple CVCs creates more points of
entry into the bloodstream, potentially increasing CLABSI risk. Multiple CVCs may
be used in sicker patients, making it difficult to separate the relative
contributions of multiple CVCs and comorbidities to CLABSI risk. We explored the
relative impact of multiple CVCs, patient comorbidities, and disease severity on
the risk of CLABSI. DESIGN: Case-control study. SETTING: A total of 197 case
patients and 201 control subjects with a CVC inserted during hospitalization at a
tertiary care academic medical center from January 1, 2008, to December 31, 2010.
METHODS: Multiple CVCs was the exposure of interest; the primary outcome was
CLABSI. Multivariable logistic regression was conducted to estimate odds ratios
(ORs) and 95% confidence intervals (CIs) describing the association between
CLABSI and multiple CVCs with and without controlling for Acute Physiology and
Chronic Health Evaluation (APACHE) II and Charlson comorbidity index (CCI) scores
as measures of disease severity and patient comorbidities, respectively. RESULTS:
Patients with multiple CVCs (n = 78) showed a 4.2 (95% CI, 2.2-8.4) times greater
risk of CLABSI compared with patients with 1 CVC after adjusting for CLABSI risk
factors. When including APACHE II and CCI scores, multiple CVCs remained an
independent risk factor for CLABSI (OR, 3.4 [95% CI, 1.7-6.9]). CONCLUSIONS:
Multiple CVCs is an independent risk factor for CLABSI even after adjusting for
severity of illness. Adjustment for this risk may be necessary to accurately
compare rates between hospitals.
PMID- 25111923
TI - Usability and impact of a computerized clinical decision support intervention
designed to reduce urinary catheter utilization and catheter-associated urinary
tract infections.
AB - OBJECTIVE: To evaluate the usability and effectiveness of a computerized clinical
decision support (CDS) intervention aimed at reducing the duration of urinary
tract catheterizations. DESIGN: Retrospective cohort study. SETTING: Academic
healthcare system. PATIENTS: All adult patients admitted from March 2009 through
May 2012. INTERVENTION: A CDS intervention was integrated into a commercial
electronic health record. Providers were prompted at order entry to specify the
indication for urinary catheter insertion. On the basis of the indication chosen,
providers were alerted to reassess the need for the urinary catheter if it was
not removed within the recommended time. Three time periods were examined:
baseline, after implementation of the first intervention (stock reminder), and
after a second iteration (homegrown reminder). The primary endpoint was the
usability of the intervention as measured by the proportion of reminders through
which providers submitted a remove urinary catheter order. Secondary endpoints
were the urinary catheter utilization ratio and the rate of hospital-acquired
catheter-associated urinary tract infections (CAUTIs). RESULT: The first
intervention displayed limited usability, with 2% of reminders resulting in a
remove order. Usability improved to 15% with the revised reminder. The catheter
utilization ratio declined over the 3 time periods (0.22, 0.20, and 0.19,
respectively; P < .001), as did CAUTIs per 1,000 patient-days (0.84, 0.70, and
0.51, respectively; P < .001). CONCLUSIONS: A urinary catheter removal reminder
system was successfully integrated within a healthcare system's electronic health
record. The usability of the reminder was highly dependent on its user interface,
with a homegrown version of the reminder resulting in higher impact than a stock
reminder.
PMID- 25111924
TI - Preventing the transmission of multidrug-resistant organisms: modeling the
relative importance of hand hygiene and environmental cleaning interventions.
AB - OBJECTIVE: Hand hygiene and environmental cleaning are essential infection
prevention strategies, but the relative impact of each is unknown. This
information is important in assessing resource allocation. METHODS: We developed
an agent-based model of patient-to-patient transmission-via the hands of
transiently colonized healthcare workers and incompletely terminally cleaned
rooms-in a 20-patient intensive care unit. Nurses and physicians were modeled and
had distinct hand hygiene compliance levels on entry and exit to patient rooms.
We simulated the transmission of Acinetobacter baumannii, methicillin-resistant
Staphylococcus aureus, and vancomycin-resistant enterococci for 1 year using data
from the literature and observed data to inform model input parameters. RESULTS:
We simulated 175 parameter-based scenarios and compared the effects of hand
hygiene and environmental cleaning on rates of multidrug-resistant organism
acquisition. For all organisms, increases in hand hygiene compliance outperformed
equal increases in thoroughness of terminal cleaning. From baseline, a 2?1
improvement in terminal cleaning compared with hand hygiene was required to match
an equal reduction in acquisition rates (eg, a 20% improvement in terminal
cleaning was required to match the reduction in acquisition due to a 10%
improvement in hand hygiene compliance). CONCLUSIONS: Hand hygiene should remain
a priority for infection control programs, but environmental cleaning can have
significant benefit for hospitals or individual hospital units that have either
high hand hygiene compliance levels or low terminal cleaning thoroughness.
PMID- 25111925
TI - Establishing evidence-based criteria for directly observed hand hygiene
compliance monitoring programs: a prospective, multicenter cohort study.
AB - OBJECTIVE: Hand hygiene surveillance programs that rely on direct observations of
healthcare worker activity may be limited by the Hawthorne effect. In addition,
comparing compliance rates from period to period requires adequately sized
samples of observations. We aimed to statistically determine whether the
Hawthorne effect is stable over an observation period and statistically derive
sample sizes of observations necessary to compare compliance rates. DESIGN:
Prospective multicenter cohort study. SETTING: Five intensive care units and 6
medical/surgical wards in 3 geographically distinct acute care hospitals.
METHODS: Trained observers monitored hand hygiene compliance during routine care
in fixed 1-hour periods, using a standardized collection tool. We estimated the
impact of the Hawthorne effect using empirical fluctuation processes and F tests
for structural change. Standard sample-size calculation methods were used to
estimate how many hand hygiene opportunities are required to accurately measure
hand hygiene across various levels of baseline and target compliance. RESULTS:
Exit hand hygiene compliance increased after 14 minutes of observation (from
56.2% to 60.5%; P < .001) and increased further after 50 minutes (from 60.5% to
66.0%; P < .001). Entry compliance increased after 38 minutes (from 40.4% to
43.4%; P = .005). Between 79 and 723 opportunities are required during each
period, depending on baseline compliance rates (range, 35%-90%) and targeted
improvement (5% or 10%). CONCLUSIONS: Limiting direct observation periods to
approximately 15 minutes to minimize the Hawthorne effect and determining
required number of hand hygiene opportunities observed per period on the basis of
statistical power calculations would be expected to improve the validity of hand
hygiene surveillance programs.
PMID- 25111926
TI - A cluster of Mycobacterium wolinskyi surgical site infections at an academic
medical center.
AB - OBJECTIVE: To study a cluster of Mycobacterium wolinskyi surgical site infections
(SSIs). DESIGN: Observational and case-control study. SETTING: Academic hospital.
PATIENTS: Subjects who developed SSIs with M. wolinskyi following cardiothoracic
surgery. METHODS: Electronic surveillance was performed for case finding as well
as electronic medical record review of infected cases. Surgical procedures were
observed. Medical chart review was conducted to identify risk factors. A case
control study was performed to identify risk factors for infection; Fisher exact
or Kruskal-Wallis tests were used for comparisons of proportions and medians,
respectively. Patient isolates were studied using pulsed-field gel
electrophoresis (PFGE). Environmental microbiologic sampling was performed in
operating rooms, including high-volume water sampling. RESULTS: Six definite
cases of M. wolinskyi SSI following cardiothoracic surgery were identified during
the outbreak period (October 1, 2008-September 30, 2011). Having cardiac surgery
in operating room A was significantly associated with infection (odds ratio, 40;
P = .0027). Observational investigation revealed a cold-air blaster exclusive to
operating room A as well a microbially contaminated, self-contained water source
used in heart-lung machines. The isolates were indistinguishable or closely
related by PFGE. No environmental samples were positive for M. wolinskyi.
CONCLUSIONS: No single point source was established, but 2 potential sources,
including a cold-air blaster and a microbially contaminated, self-contained water
system used in heart-lung machines for cardiothoracic operations, were
identified. Both of these potential sources were removed, and subsequent active
surveillance did not reveal any further cases of M. wolinskyi SSI.
PMID- 25111927
TI - Translating evidence into practice using a systems engineering framework for
infection prevention.
PMID- 25111929
TI - Intraoperative stopcock and manifold colonization of newly inserted peripheral
intravenous catheters.
PMID- 25111930
TI - Electronic monitoring of individual healthcare workers' hand hygiene event rate.
PMID- 25111928
TI - High prevalence of reduced chlorhexidine susceptibility in organisms causing
central line-associated bloodstream infections.
AB - In units that bathe patients daily with chlorhexidine gluconate (CHG), organisms
causing central line-associated bloodstream infections (CLABSIs) were more likely
to have reduced CHG susceptibility than organisms causing CLABSIs in units that
do not bathe patients daily with CHG (86% vs 64%; P = .028). Surveillance is
needed to detect reduced CHG susceptibility with widespread CHG use.
PMID- 25111931
TI - Anatomic sites of colonization with community-associated methicillin-resistant
Staphylococcus aureus.
PMID- 25111932
TI - Discordance between novel and traditional surveillance paradigms of ventilator
associated pneumonia.
PMID- 25111933
TI - Discordance between novel and traditional surveillance definitions for ventilator
associated pneumonia: insights and opportunities to improve patient care.
PMID- 25111934
TI - Impact of physicians' mindfulness attitudes toward prevention of catheter
associated urinary tract infection.
PMID- 25111935
TI - A formula for infection control using colonization pressure and compliance rates.
PMID- 25111936
TI - Epidemiology of sharps injury and splash exposure in an oncology care center in
eastern India.
PMID- 25111937
TI - Multidrug-resistant gram-negative bacteria in hematology and oncology.
PMID- 25111938
TI - Port-related Aeromonas bacteremia.
PMID- 25111939
TI - Tuberculosis infection control: potential benefit of a new rapid tuberculosis
test in a human immunodeficiency virus/AIDS reference hospital.
PMID- 25111942
TI - Relapse following antithyroid drug therapy for Graves' hyperthyroidism.
AB - PURPOSE OF REVIEW: In most patients with hyperthyroidism caused by Graves'
disease, antithyroid drug (ATD) therapy is followed by a gradual amelioration of
the autoimmune abnormality, but about half of the patients will experience
relapse of hyperthyroidism when the ATDs are withdrawn after a standard 1 to 2
years of therapy. This is a major drawback of ATD therapy, and a major concern to
patients. We review current knowledge on how to predict and possibly reduce the
risk of such relapse. RECENT FINDINGS: Several patient and disease
characteristics, as well as environmental factors and duration of ATD therapy,
may influence the risk of relapse after ATD withdrawal. Depending on the presence
of such factors, the risk of relapse after ATD withdrawal may vary from around 10
to 90%. Risk factors for relapse should be taken into account when choosing
between therapeutic modalities in a patient with newly diagnosed disease, and
also when discussing duration of ATD therapy. SUMMARY: Prolonged low-dose ATD
therapy may be feasible in patients with high risk of relapse, such as children
and patients with active Graves' orbitopathy, and in patients with previous
relapse who prefer such therapy rather than surgery or radioiodine.
PMID- 25111941
TI - Molecular evidence of cryptic diversity in Paracaryophyllaeus (Cestoda:
Caryophyllidea), parasites of loaches (Cobitidae) in Eurasia, including
description of P. vladkae n. sp.
AB - Molecular phylogenetic analysis of an extensive collection of monozoic tapeworms
of the genus Paracaryophyllaeus Kulakovskaya, 1961 (Cestoda: Caryophyllidea),
parasites of loaches (Cypriniformes: Cobitidae) in Eurasia, has revealed cryptic
species diversity within this long-time monotypic genus, especially in the
Paracaryophyllaeus gotoi (Motomura, 1927) species complex [syn.
Paracaryophyllaeus dubininorum (Kulakovskaya, 1961); type species]. Three
independent, well-supported clades were discovered on the basis of molecular
data: (i) specimens from Misgurnus anguillicaudatus and Cobitis lutheri from
China, Russian Far East and Japan - called herein P. cf. gotoi 1, which may be
conspecific with P. gotoi (Motomura, 1927), although in the absence of sequence
data for P. gotoi from its type locality (basin of the River Kumkan in Korea), no
certain inferences about their identity can currently be made; (ii) specimens
from M. anguillicaudatus from China and Japan - P. cf. gotoi 2, which are
morphologically indistinguishable from those of P. cf. gotoi 1; and (iii)
morphologically distinct tapeworms from the endemic loach Cobitis bilseli from
southwestern Turkey (Beysehir Lake), which are described herein as a new species.
Paracaryophyllaeus vladkae Scholz, Oros and Aydogdu n. sp. differs from the
remaining species of the genus in the following characteristics: the testes begin
anterior to the first vitelline follicles (versus posterior), the body is short
and robust (versus more elongate and slender), and the scolex is wide, rounded or
apically tapered (versus claviform to truncate). Species composition of the
genus, host specificity of species and geographical distribution are briefly
discussed.
PMID- 25111943
TI - Sleeve gastrectomy and Roux En Y gastric bypass: current state of metabolic
surgery.
AB - PURPOSE OF REVIEW: Roux En Y gastric bypass (RYGB) is considered the bariatric
gold standard. Recently, sleeve gastrectomy has gained significant popularity.
Early evidence suggests sleeve gastrectomy as a well tolerated and efficacious
alternative to RYGB. This article compares RYGB and sleeve gastrectomy by
reviewing and summarizing recently published clinical trials. RECENT FINDINGS:
Surgery remains the most effective therapy for obese patients meeting criteria.
Excess weight loss in short-term follow-up appears similar between RYGB and
sleeve gastrectomy. Long-term data on sleeve gastrectomy are limited. RYGB is
more effective in producing resolution and remission of type II diabetes
mellitus, particularly in patients at high risk for relapse. RYGB and sleeve
gastrectomy are similar in their reduction of other obesity-related comorbid
conditions with the exception of gastroesophageal reflux disease. RYGB has
slightly higher overall morbidity but mortality is similar. SUMMARY: RYGB and
sleeve gastrectomy are well tolerated and effective bariatric operations and
represent metabolic surgery. More prospective, long-term data are needed. Both
procedures benefit specific groups of patients better than the other. Research
defining the obese patient's metabolic state and the metabolic response to both
operations will ultimately allow physicians to optimally match patient and
procedure.
PMID- 25111944
TI - How long should patients remain in the supine treatment position after
intratympanic dexamethasone injection?
AB - OBJECTIVES/HYPOTHESIS: Intratympanic dexamethasone injection (ITDI) is a widely
accepted treatment for patients with sudden hearing loss. We investigated the
appropriate patient wait time in the supine treatment position after ITDI. STUDY
DESIGN: Prospective study. METHODS: In an in vivo animal study, 24 mice were
injected intratympanically with dexamethasone. Perilymphatic fluid was sampled at
5, 10, 15, 20, 25, and 30 minutes postinjection. The dexamethasone concentration
was analyzed using high-performance liquid chromatography. In a separate
prospective clinical study, 79 patients with refractory sudden hearing loss
underwent intratympanic injection. After the injection, patients remained in the
supine position with the head rotated 45 degrees to the unaffected side.
Patients were divided into two groups according to the wait time in this
treatment position postinjection: 30 minutes (n = 47) and 10 minutes (n = 32).
Final hearing assessments were conducted 2 months after salvage treatment.
RESULTS: In the in vivo animal study, the perilymphatic concentration of
dexamethasone showed no significant increase after 10 minutes. In the clinical
setting, hearing improvement according to Siegel's criteria was similar in the 30
minute (14/47) and 10-minute (10/32) groups (P = 0.999). No significant
differences in relative hearing gain was observed between the two groups (13.80
+/- 19.9 dB and 12.57 +/- 14.9 dB, respectively; P = 0.766). CONCLUSION: We
suggest that 10 minutes is a sufficient time to remain in the supine treatment
position after ITDI in patients with sudden hearing loss. LEVEL OF EVIDENCE: N/A.
PMID- 25111945
TI - Transient osteoporosis of pregnancy of the bilateral hips in twin gestation: a
case series.
AB - Transient osteoporosis of pregnancy has been described as a rare, self-limiting
disease of unclear etiology that presents as severe pain, which typically affects
pregnant women in their third trimester. We describe 3 cases of primigravid
pregnant women with twin gestation who reported unilateral hip pain and who were
diagnosed with transient osteoporosis of pregnancy of the hip by magnetic
resonance imaging. These women were advised to undergo limited weight bearing and
activity modification to minimize the risk of fracture. Each patient was able to
proceed through her pregnancy, delivery, and postpartum course without
complication, with symptom resolution, and return to unrestricted activity.
PMID- 25111946
TI - Single leg squat test and its relationship to dynamic knee valgus and injury risk
screening.
AB - BACKGROUND: Lower extremity injuries are common in athletes. Valid tests to
assess for risk of injury that are easily performed during a preparticipation
sports physical examination are lacking. Two-dimensional (2D) analysis of the
drop-jump test can identify athletes at risk, but it is too expensive and
cumbersome to use in this setting. OBJECTIVE: To identify if those who perform a
"positive"(abnormal postures) single leg squat (SLS) test also exhibit greater
"dynamic valgus" on the 2D drop-jump test. Our secondary purpose was to assess
whether group differences in gender, age, or body mass index are evident between
those who exhibit a positive SLS test result versus a negative SLS test result.
Also, we wanted to determine any gender differences with the 2D drop-jump test.
DESIGN: A cross-sectional study. SETTING: Private practice, preparticipation
sports physical examinations. PARTICIPANTS: A total of 142 middle school and high
school athletes. METHODS: Participants performed a SLS test and a drop-jump test
during their preparticipation sports physical examination. Individuals were
partitioned into groups based on the outcome of their SLS test (positive SLS
group versus negative SLS group). Independent sample t-tests were used to
evaluate SLS group differences in the drop-jump test, age, and body mass index,
and the chi(2) test was used to evaluate SLS group differences in gender (P <=
.05). MAIN OUTCOME MEASUREMENTS: The SLS test and drop-jump test. RESULTS:
Seventy-three of the 142 athletes (51%) had a positive SLS test result, whereas
69 athletes (49%) had a negative SLS test result. Individuals in the positive SLS
group had a significantly lower knee-hip ratio), indicative of greater dynamic
knee valgus, than did those in the negative SLS group (P = .02). Individual
characteristics between SLS groups including gender, age, and body mass index
were similar. CONCLUSION: The SLS test is a reasonable tool to use in
preparticipation sports physical examinations to assess for dynamic knee valgus
and the potential risk of lower extremity injury.
PMID- 25111947
TI - Detection of DNA damage in peripheral blood mononuclear cells from pancreatic
cancer patients.
AB - DNA repair is a key mechanism in maintaining genomic stability: repair
deficiencies increase DNA damage and mutations that lead to several diseases,
including cancer. We extracted DNA from peripheral blood mononuclear cells
(PBMCs) of 48 pancreatic adenocarcinoma cases and 48 healthy controls to
determine relative levels of nuclear DNA (nDNA) and mitochondrial DNA (mtDNA)
damage by QPCR. All participants were never smokers and between the ages of 60
and 69. Average levels among cases were compared to controls using a rank sum
test, and logistic regression adjusted for potential confounding factors (age,
sex, and diabetes mellitus). Cases had less DNA damage, with a significant
decrease in mtDNA damage (P-value = 0.03) and a borderline significant decrease
in nDNA damage (P = 0.08). Across samples, we found mtDNA abundance was higher
among non-diabetics compared to diabetics (P = 0.04). Our results suggest that
patients with pancreatic adenocarcinoma have less DNA damage in their PBMCs, and
that having diabetes, a known pancreatic cancer risk factor, is associated with
lower levels of mtDNA abundance.
PMID- 25111949
TI - Transposition of the left renal vein for the treatment of nutcracker syndrome in
children: a short-term experience.
AB - BACKGROUND: Nutcracker syndrome is caused by compression of the left renal vein
between the superior mesenteric artery and the aorta. Invasive surgical
intervention for this pathologic entity is controversial, particularly in the
pediatric population. We aim to describe our early clinical and operative
experience with such patients. METHODS: We report 3 cases of pediatric patients
undergoing successful left renal vein transposition for the treatment of
nutcracker syndrome. RESULTS: All 3 patients were female (age 9-17 years) and
presented with a mean of 11.7 months of abdominal or left flank pain requiring
chronic narcotic analgesia. Initial clinical presentations were associated with
either hematuria or proteinuria. Diagnosis of nutcracker syndrome was supported
in each case by an elevated renocaval pressure gradient and/or axial imaging
demonstrating mesoaortic compression of the left renal vein. All patients
underwent open surgical repair, which included left renal vein transposition,
liberation of the ligament of Treitz and associated adhesions, as well as
excision of periaortic nodal tissue (mean hospital length of stay 5.7 days).
After mean follow-up of 13 months, all patients report complete resolution of
symptoms and hematuria/proteinuria. CONCLUSIONS: Transposition of the left renal
vein is a safe and effective treatment for nutcracker syndrome in appropriately
selected pediatric patients. Further experience and long-term follow-up are
warranted to better evaluate the sustained efficacy of this procedure in this
unique patient population.
PMID- 25111948
TI - White-matter relaxation time and myelin water fraction differences in young
adults with autism.
AB - BACKGROUND: Increasing evidence suggests that autism is associated with abnormal
white-matter (WM) anatomy and impaired brain 'connectivity'. While myelin plays a
critical role in synchronized brain communication, its aetiological role in
autistic symptoms has only been indirectly addressed by WM volumetric,
relaxometry and diffusion tensor imaging studies. A potentially more specific
measure of myelin content, termed myelin water fraction (MWF), could provide
improved sensitivity to myelin alteration in autism. METHOD: We performed a cross
sectional imaging study that compared 14 individuals with autism and 14 age- and
IQ-matched controls. T 1 relaxation times (T 1), T 2 relaxation times (T 2) and
MWF values were compared between autistic subjects, diagnosed using the Autism
Diagnostic Interview - Revised (ADI-R), with current symptoms assessed using the
Autism Diagnostic Observation Schedule (ADOS) and typical healthy controls.
Correlations between T 1, T 2 and MWF values with clinical measures [ADI-R, ADOS,
and the Autism Quotient (AQ)] were also assessed. RESULTS: Individuals with
autism showed widespread WM T 1 and MWF differences compared to typical controls.
Within autistic individuals, worse current social interaction skill as measured
by the ADOS was related to reduced MWF although not T 1. No significant
differences or correlations with symptoms were observed with respect to T 2.
CONCLUSIONS: Autistic individuals have significantly lower global MWF and higher
T 1, suggesting widespread alteration in tissue microstructure and biochemistry.
Areas of difference, including thalamic projections, cerebellum and cingulum,
have previously been implicated in the disorder; however, this is the first study
to specifically indicate myelin alteration in these regions.
PMID- 25111950
TI - Isolated dissecting aneurysms of the abdominal aorta and the superior mesenteric
artery. A case report and literature review.
AB - Supracoeliac abdominal aortic dissections are rare and require complex
interventions for repair. Superior mesenteric artery (SMA) dissections are also
rare and even less frequently reported to involve aneurysmal change. We present
the case of a 65-year-old man with a dissecting supracoeliac aortoiliac aneurysm
and a separate dissecting aneurysm of the SMA The surgical intervention performed
and a review of the literature on the management of SMA dissection in the
endovascular era are presented.
PMID- 25111951
TI - Antiinflammatory properties of the stem-bark of Anopyxis klaineana and its major
constituent, methyl angolensate.
AB - Anopyxis klaineana (Pierre) Engl. (Rhizophoraceae) is one of the reputed West
African folkloric medicines that has never been investigated for its
pharmacological effects or phytochemical constituents. In the present study, the
antiinflammatory properties of the stem-bark extracts were evaluated using the
carrageenan-induced paw oedema model in chicks. The petroleum ether, ethyl
acetate and methanol extracts all showed a time and dose-dependent
antiinflammatory effect over the 5-h observation period. Phytochemical analysis
of the most active extract (methanol extract) yielded the principal constituent
that was identified as methyl angolensate through extensive spectroscopic and X
ray analysis studies. Although slightly less potent (ED50 , 4.05 +/- 0.0034
mg/kg, orally) than the positive control, diclofenac (ED50 , 2.49 +/- 0.023,
intraperitoneally n = 5), this first ever compound isolated from A. klaineana
showed promising antiinflammatory activity that may account to some of the
reported medicinal uses of the plant.
PMID- 25111952
TI - Importance of diameter control on selective synthesis of semiconducting single
walled carbon nanotubes.
AB - The coexistence of semiconducting and metallic single-walled carbon nanotubes
(SWNTs) during synthesis is one of the major bottlenecks that prevent their broad
application for the next-generation nanoelectronics. Herein, we present more
understanding and demonstration of the growth of highly enriched semiconducting
SWNTs (s-SWNTs) with a narrow diameter distribution. An important fact discovered
in our experiments is that the selective elimination of metallic SWNTs (m-SWNTs)
from the mixed arrays grown on quartz is diameter-dependent. Our method
emphasizes controlling the diameter distribution of SWNTs in a narrow range where
m-SWNTs can be effectively and selectively etched during growth. In order to
achieve narrow diameter distribution, uniform and stable Fe-W nanoclusters were
used as the catalyst precursors. About 90% of as-prepared SWNTs fall into the
diameter range 2.0-3.2 nm. Electrical measurement results on individual SWNTs
confirm that the selectivity of s-SWNTs is ~95%. The present study provides an
effective strategy for increasing the purity of s-SWNTs via controlling the
diameter distribution of SWNTs and adjusting the etchant concentration.
Furthermore, by carefully comparing the chirality distributions of Fe-W-catalyzed
and Fe-catalyzed SWNTs under different water vapor concentrations, the
relationship between the diameter-dependent and electronic-type-dependent etching
mechanisms was investigated.
PMID- 25111953
TI - Inverse effect of mucinous component on survival in stage III colorectal cancer.
AB - BACKGROUND: Although mucinous adenocarcinoma (MAC) is has been recognized as a
separate entity in colorectal cancer (CRC), adenocarcinoma with a mucinous
component (ACM) remains poorly understood. METHODS: The association of MAC and
ACM with disease-free survival (DFS) and overall survival (OS) was examined using
the Cox proportional hazard model in 425 consecutive stage III CRCs. RESULTS:
Compared with conventional adenocarcinoma (CAC), patients with MAC exhibited
independently worse DFS (hazard ratio [HR], 2.64; 95% CI, 1.21-5.80; P = 0.014)
and OS (HR, 3.56; 95% CI, 1.53-8.30; P = 0.003). Unexpectedly, ACM was
significantly associated with worse OS than CAC (P = 0.002), despite having a
similar DFS to CAC. Further, ACM patients after recurrence exhibited
significantly worse OS than CAC patients (P < 0.001), similar to MAC.
CONCLUSIONS: Although ACM is similar to CAC with regard to estimated risk of
recurrence, the outcome is extremely poor once recurrence occurs and is identical
to MAC; one of the most aggressive phenotypes of stage III CRC. Thus, both MAC
and ACM are adverse prognostic factors for OS.
PMID- 25111954
TI - Surveillance colonoscopy in elderly patients: a retrospective cohort study.
AB - IMPORTANCE: The risks and benefits of surveillance colonoscopy in elderly
patients have not been well characterized. OBJECTIVE: To investigate the relative
impact of surveillance colonoscopy in elderly patients compared with a reference
cohort. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study from 2001
through 2010 of patients 50 years and older undergoing surveillance colonoscopy
for a history of colorectal cancer (CRC) or adenomatous polyps at an integrated
health care system in southern California. Patients were followed up from the
surveillance examination until CRC diagnosis, death, disenrollment, IBD
diagnosis, or study end date (December 31, 2010). MAIN OUTCOMES AND MEASURES: The
primary outcome measure was incidence of CRC detected following surveillance
colonoscopy. The secondary outcome was risk of procedure defined as postprocedure
hospitalization within 30 days. Cox regression and multivariable logistic
regression analyses were used to determine the impact of age on CRC incidence on
surveillance examination as well as postprocedure hospitalization, respectively.
RESULTS: The study cohort included 4834 elderly patients (age >=75 years; 55.8%
male) (median surveillance age, 79 years) and 22 929 individuals in the reference
group (age 50-74 years; 57.7% male) (median surveillance age, 63 years). A total
of 373 cancers were detected following surveillance colonoscopy (368 in the
reference group and 5 among the elderly patients). There were a total of 711
postprocedure hospitalizations (184 in the reference group and 527 among the
elderly patients). The CRC incidence among elderly patients undergoing
surveillance was 0.24 per 1000 person-years vs 3.61 per 1000 person-years in the
reference population (P < .001). In Cox regression analysis, the hazard ratio for
CRC in the elderly patients compared with the reference group was 0.06 (95% CI,
0.02-0.13) (P < .001) after adjusting for comorbid illness, sex, and
race/ethnicity. In logistic regression analysis, age 75 years and older was
independently associated with increased risk of postprocedure hospitalization
(adjusted odds ratio, 1.28 [95% CI, 1.07-1.53]; P = .006). Charlson score of 2
was also independently associated with increased risk of postprocedure
hospitalization (adjusted odds ratio, 2.54 [95% CI, 2.06-3.14]; P < .001).
CONCLUSIONS AND RELEVANCE: A low incidence of CRC and relatively high rate of
postprocedure hospitalization were found among elderly patients undergoing
surveillance colonoscopy. Recommendations for ongoing surveillance in the elderly
population should take into consideration the impact of comorbid illness and
increasing age on the anticipated risks and benefits of colonoscopy.
PMID- 25111955
TI - Family dynamics and young children's sibling victimization.
AB - This research examines how family dynamics like interparental conflict, family
violence, and quality of parenting are associated with young children's
experiences of sibling victimization. We use nationally representative data from
interviews with caregivers of 1,726 children aged 2 to 9 years of age. We
hypothesized different family dynamics predictors for a composite of common types
of sibling victimization (property, psychological, and mild physical aggression)
in comparison to severe physical sibling victimization (victimization that
includes physical aggression with a weapon and/or injury). Multinomial regression
results showed that sibling victimization in general was associated with negative
family dynamics but that children in the severe group had even less parental
warmth, poor parental supervision, and greater exposure to interparental conflict
and family violence than children in the common types victimization group.
Different aspects of family dynamics contribute to sibling victimization, but
possibly in different ways and with different consequences. The findings
underscore the importance of a family systems theory approach to clinical and
intervention work.
PMID- 25111956
TI - Shared possible selves, other-focus, and perceived wellness of couples with
prostate cancer.
AB - Shared possible selves are associated with better well-being in couples through
their engagement in and enjoyment of collaboration (Schindler, Berg, Butler,
Fortenberry, & Wiebe, 2010). The present study sought to address which partner's
other-focus accounted for this sharedness in possible selves and how the
individual and dyadic configurations of other-focused selves relate to health and
well-being (i.e., perceived wellness) in an important health context for adult
couples-prostate cancer. Sixty-one men diagnosed with prostate cancer and their
wives rated their own subjective physical health and well-being and listed
possible selves. Possible selves were reliably coded for the inclusion of the
other (i.e., other-focus), either with the other as the subject or communal in
content. Regression analysis showed that wives' other-focus, not husbands',
explained variance in shared selves. A Bayesian actor-partner interdependence
model (APIM) of both partners' other-focus and interaction between the 2 revealed
a pattern that differed by partner. The association between husband other-focus
and his perceived wellness was negative for husbands whose wives were low in
other-focus and not significant for husbands with highly other-focused wives.
Women's sense of perceived wellness did not relate to either partner's other
focus. Results support the notion that shared possible selves may be shared
unequally in couples facing chronic illness and suggest the importance of
considering both partners' other-focus to understand perceived wellness. Findings
may point to more general processes of relational adaptation to major life
stressors such as prostate cancer.
PMID- 25111957
TI - Oleanolic acid co-administration alleviates ethanol-induced hepatic injury via
Nrf-2 and ethanol-metabolizing modulating in rats.
AB - Alcoholic liver disease (ALD) is one of the leading causes of death in the world.
Oxidative stress plays an important role in the pathogenesis of alcohol-induced
liver injury. Our previous results have found that oleanolic acid (OA), a liver
protective agent, plays a potent antioxidant activity in hepatocyte. In the
present study, the protective effects of OA co-administration on ethanol-induced
oxidative injury in rats were investigated through detecting hepatic
histopathology, antioxidant enzymes, ethanol metabolic enzymes and inflammatory
factors. Preventions of ethanol-induced oxidative injury by OA were reflected by
markedly decreased serum activities of AST, ALT and significantly increased the
hepatic ATP level. In addition, the increase of the hepatic TG content, MDA level
and the decrease of hepatic GSH level, SOD activity, CAT activity induced by
ethanol were significantly inhibited by OA co-administration. Furthermore, OA
could also elevate the protein expressions and nuclear translocation of
antioxidant transcription factor Nrf-2 and then up-regulated antioxidant enzymes
expressions of HO-1, SOD-1 and GR. Moreover, OA co-administration can
significantly reduce the activity and expressions of CYP2E1 and ADH, which has
characteristic of generation ROS mediated oxidative stress and acetaldehyde
respectively. Furthermore, OA co-administration could inhibition of the
generation of inflammatory factors TNF-alpha and IL-6. Those above results
indicated that OA co-administration can protect rats against ethanol-induced
liver injury by induction Nrf-2 related antioxidant to maintain redox balance and
modulating the ethanol-metabolizing and inflammatory pathway.
PMID- 25111958
TI - Ovarian insufficiency and pubertal development after hematopoietic stem cell
transplantation in childhood.
AB - BACKGROUND: Ovarian insufficiency (OI) and infertility are common and devastating
late effects of cancer treatment and hematopoietic stem cell transplantation
(HSCT). In children, gonadal insufficiency may subsequently lead to abnormal
pubertal development. The aim of this study was to assess the cumulative
incidence of OI and the need for hormonal induction of pubertal development after
HSCT in childhood. We additionally assessed HSCT-related risk factors for OI.
PROCEDURES: A single center cohort study was undertaken of female patients
transplanted during childhood, surviving at least 2 years post-HSCT and who were
at least 10 years old at initiation of the study. Of 141 eligible patients, 109
were included and hormone levels and clinical data of these patients during
follow-up were collected. Risk factors for OI were analyzed by multivariate Cox
regression analysis. RESULTS: Cumulative incidence of OI was 56% at a median
follow-up of 7.2 years. Eight patients, initially diagnosed with OI, showed
recovery of ovarian function over time. Hormonal induction of puberty was
necessary in 44% of females who were pre-pubertal or pubertal at HSCT. In
multivariate analysis, more advanced pubertal stage at HSCT was associated with
OI. We found a trend for an association of busulfan with OI in patients
conditioned with chemotherapy only. CONCLUSIONS: The incidence of OI after HSCT
was high and associated with more advanced pubertal stage at HSCT. Almost half of
the females who were pre-pubertal or pubertal at HSCT required hormonal induction
of pubertal development.
PMID- 25111959
TI - Pharmacokinetic profile and first preliminary clinical evaluation of bendamustine
in Taiwanese patients with heavily pretreated indolent B-cell non-Hodgkin
lymphoma and mantle cell lymphoma.
AB - Prior studies found bendamustine is efficacious in patients with indolent B-cell
non-Hodgkin lymphoma (NHL). To date, no studies have reported the efficacy of
bendamustine in a Chinese population. This multicentre phase II trial evaluated
the pharmacokinetics (PK), safety and efficacy of bendamustine monotherapy in
Chinese patients in Taiwan with pretreated indolent B-cell NHL or mantle cell
lymphoma (MCL). For PK assessments, patients were randomized (n = 16; 11 with
indolent B-cell NHL and five with MCL) to 90 or 120 mg/m(2) of bendamustine for
the first cycle. Plasma levels of bendamustine and its two metabolites were
analyzed. For efficacy and safety evaluations, bendamustine 120 mg/m(2) was given
to all patients every 3 weeks starting at cycle 2 for a minimum of a total of six
cycles. The median age of patients was 61.7 years, and the majority were men
(75%). The median number of prior treatments was 4 (range, 1-9 regimens), and all
patients were previously treated with rituximab. Bendamustine plasma
concentration peaked near the end of infusion and was rapidly eliminated with a
mean elimination half-life (t(1/2)) of 0.67-0.8 h. Of the evaluable patients (n =
14), the overall response rate was 78.6%, including 7.2% of patients having a
complete response. Mean progression-free survival was 27.5 weeks. The most common
grade 3-4 adverse events were leucopenia (56.3%), neutropenia (56.3%) and
thrombocytopenia (25%). In conclusion, bendamustine was efficacious and well
tolerated in Taiwanese patients with indolent NHL and MCL with a similar PK
profile to that of other populations.
PMID- 25111960
TI - Emission-tunable CuInS2/ZnS quantum dots: structure, optical properties, and
application in white light-emitting diodes with high color rendering index.
AB - Synthesis and application of CuInS2/ZnS core/shell quantum dots (QDs) with
varying [Cu]/[In] ratios were conducted using a stepwise solvothermal route.
CuInS2 (CIS) core QDs with varying [Cu]/[In] ratios exhibited deep-red emissions
result from donor-acceptor pair recombination. The absorption and emission band
gap of the CuInS2 QDs increased with the decrease in Cu content. The emission
bands of the CuInS2/ZnS were tuned from 550 to 616 nm by controlling the
[Cu]/[In] ratio after coating ZnS layer. The CIS QDs model was developed to
elucidate the synthesized crystal structure and photoluminescence of the QDs with
various [Cu]/[In] ratios. Temperature-dependent photoluminescence spectra of the
CIS/ZnS QDs were also investigated. The temperature dependency of the
photoluminescence energy and intensity for various CIS/ZnS QDs were studied from
25 to 200 degrees C. Efficient white light-emitting diodes with high color
rendering index values (Ra = 90) were fabricated using CIS/ZnS QDs as color
converters in combination with green light-emitting Ba2SiO4:Eu(2+) phosphors and
blue light-emitting diodes.
PMID- 25111961
TI - Systematic review of pharmacological treatments for depressive symptoms in
Huntington's disease.
AB - BACKGROUND: Depressive symptoms are common in Huntington's disease (HD),
profoundly affect quality of life, and predict suicidal ideation. However, no
recent review of antidepressant treatment in HD has been published. METHODS: We
performed a PRISMA systematic review of HD studies, which used a recognized
antidepressant and measured change in depressive symptoms using a validated
psychiatric scale. Controlled trials, uncontrolled trials, observational studies,
and case series were included. RESULTS: Eleven studies were included, totalling
190 patients. One study examined venlafaxine, one fluoxetine, one citalopram, one
atomoxetine, one modafinil, one lithium, and five antipsychotics. No studies were
of adequate duration, size, or outcome, and no controlled trial in a depressed
population produced a positive result. CONCLUSIONS: Inadequate evidence exists to
guide antidepressant treatment in HD. Further research is needed to assess
antidepressant efficacy and to examine whether treatment of depression represents
a modifiable target for the high suicide rate in HD.
PMID- 25111962
TI - Regulatory decision-making: are we getting it right?
PMID- 25111963
TI - Development of a new benzylating reagent spontaneously releasing benzyl cation
equivalents at room temperature.
AB - A new O-benzylating reagent, that is, 4-(4,6-diphenoxy-1,3,5-triazin-2-yl)-4
benzylmorpholinium trifluoromethanesulfonate (DPT-BM), has been developed. Benzyl
cation equivalents are generated from DPT-BM by dissolving the compound in a
solvent at room temperature under non-acidic conditions. The benzylation of
various alcohols by using a combination of DPT-BM and magnesium oxide provided
the benzyl ethers in good yields.
PMID- 25111964
TI - SLaP mapper: a webserver for identifying and quantifying spliced-leader addition
and polyadenylation site usage in kinetoplastid genomes.
AB - The Kinetoplastida are a diverse and globally distributed class of free-living
and parasitic single-celled eukaryotes that collectively cause a significant
burden on human health and welfare. In kinetoplastids individual genes do not
have promoters, but rather all genes are arranged downstream of a small number of
RNA polymerase II transcription initiation sites and are thus transcribed in
polycistronic gene clusters. Production of individual mRNAs from this continuous
transcript occurs co-transcriptionally by trans-splicing of a ~39 nucleotide
capped RNA and subsequent polyadenylation of the upstream mRNA. SLaP mapper
(Spliced-Leader and Polyadenylation mapper) is a fully automated web-service for
identification, quantitation and gene-assignment of both spliced-leader and
polyadenylation addition sites in Kinetoplastid genomes. SLaP mapper only
requires raw read data from paired-end Illumina RNAseq and performs all read
processing, mapping, quality control, quantification, and analysis in a fully
automated pipeline. To provide usage examples and estimates of the quantity of
sequence data required we use RNAseq obtained from two different library
preparations from both Trypanosoma brucei and Leishmania mexicana to show the
number of expected reads that are obtained from each preparation type. SLaP
mapper is an easy to use, platform independent webserver that is freely available
for use at http://www.stevekellylab.com/software/slap. Example files are provided
on the website.
PMID- 25111965
TI - The revolution of whole genome sequencing to study parasites.
AB - Genome sequencing has revolutionized the way in which we approach biological
research from fundamental molecular biology to ecology and epidemiology. In the
last 10 years the field of genomics has changed enormously as technology has
improved and the tools for genomic sequencing have moved out of a few dedicated
centers and now can be performed on bench-top instruments. In this review we will
cover some of the key discoveries that were catalyzed by some of the first genome
projects and discuss how this field is developing, what the new challenges are
and how this may impact on research in the near future.
PMID- 25111966
TI - Characterization of recombinant malarial RecQ DNA helicase.
AB - RecQ DNA gene of multi-drug resistant Plasmodium falciparum K1 (PfRecQ1) was
cloned, and the recombinant C-terminal-decahistidine-tagged PfRecQ1 was expressed
in Escherichia coli. The purified enzyme could efficiently unwind partial duplex
DNA substrate in a 3' to 5' direction. The malarial RecQ1 could not unwind
substrates with both 5' and 3' overhangs, those with a 5' overhang, or blunt
ended DNA duplexes. Unwinding of DNA helicase activity was driven by the
hydrolysis of ATP. The drug inhibitory effects of six compounds indicated that
only doxorubicin and daunorubicin could inhibit the unwinding activity.
PMID- 25111968
TI - Development, validation and characterization of a novel mouse model of Adynamic
Bone Disease (ABD).
AB - The etiology of Adynamic Bone Disease (ABD) is poorly understood but the hallmark
of ABD is a lack of bone turnover. ABD occurs in renal osteodystrophy (ROD) and
is suspected to occur in elderly patients on long-term anti-resorptive therapy. A
major clinical concern of ABD is diminished bone quality and an increased
fracture risk. To our knowledge, experimental animal models for ABD other than
ROD-ABD have not been developed or studied. The objectives of this study were to
develop a mouse model of ABD without the complications of renal ablation, and to
characterize changes in bone quality in ABD relative to controls. To re-create
the adynamic bone condition, 4-month old female Col2.3Deltatk mice were treated
with ganciclovir to specifically ablate osteoblasts, and pamidronate was used to
inhibit osteoclastic resorption. Four groups of animals were used to characterize
bone quality in ABD: Normal bone controls, No Formation controls, No Resorption
controls, and an Adynamic group. After a 6-week treatment period, the animals
were sacrificed and the bones were harvested for analyses. Bone quality
assessments were conducted using established techniques including bone histology,
quantitative backscattered electron imaging (qBEI), dual energy X-ray
absorptiometry (DXA), microcomputed tomography (microCT), and biomechanical
testing. Histomorphometry confirmed osteoblast-related hallmarks of ABD in our
mouse model. Bone formation was near complete suppression in the No Formation and
Adynamic specimens. Inhibition of bone resorption in the Adynamic group was
confirmed by tartrate-resistant acid phosphatase (TRAP) stain. Normal bone
mineral density and architecture were maintained in the Adynamic group, whereas
the No Formation group showed a reduction in bone mineral content and trabecular
thickness relative to the Adynamic group. As expected, the No Formation group had
a more hypomineralized profile and the Adynamic group had a higher mean
mineralization profile that is similar to suppressed bone turnover in human. This
data confirms successful replication of the adynamic bone condition in a mouse
without the complication of renal ablation. Our approach is the first model of
ABD that uses pharmacological manipulation in a transgenic mouse to mimic the
bone cellular dynamics observed in the human ABD condition. We plan to use our
mouse model to investigate the adynamic bone condition in aging and to study
changes to bone quality and fracture risk as a consequence of over-suppressed
bone turnover.
PMID- 25111970
TI - Outcomes in operative management of pancreatic cancer.
AB - Pancreatic cancer is a highly lethal malignancy that often presents at an
advanced stage. Surgical resection can prolong survival and offers the only
potential for cure. However, pancreatectomy is associated with significant
morbidity and mortality. This article reviews perioperative outcomes, post
resection long-term survival, and innovations in the surgical management of
pancreatic cancer.
PMID- 25111971
TI - The use of 3D power Doppler ultrasound in the quantification of blood vessels in
uterine fibroids: feasibility and reproducibility.
AB - BACKGROUND: To evaluate the interobserver agreement and discriminating value of
three-dimensional power Doppler ultrasound (3D PDUS) in patients with fibroids.
METHODS: An observational prospective cohort study in 19 patients with fibroids.
3D PDUS was performed by one examiner and evaluated by three independent
examiners in order to evaluate various vascular parameters: vascular index (VI),
flow index, and vascular flow index of the fibroid, the vascular capsule and of
its highest vascular area, using both manual and automatic contour modes. The
intraclass correlation coefficient and discriminating values were calculated. The
correlation between VI and volume was studied using Kendall's Tau test. RESULTS:
In the manual contour mode, the VIs of the fibroid and of the vascular capsule
had the highest interobserver agreements (intraclass correlation coefficients of
0.89 and 0.87, respectively). Both parameters seem to have good discriminating
values, given the large range of these parameters between different fibroids,
independent of their volume. The vascularity of the fibroid and capsule was
related. VI was not related to the volume of the fibroid. CONCLUSIONS: VI
assessed using 3D PDUS is a reproducible parameter in the assessment of fibroid
vascularization with discriminating abilities. Additional studies are needed to
further evaluate its validity and clinical relevance.
PMID- 25111972
TI - Response to "'Everybody's plastic": so what?'.
PMID- 25111969
TI - Monitoring oxygen levels in orthotopic human glioma xenograft following carbogen
inhalation and chemotherapy by implantable resonator-based oximetry.
AB - Hypoxia is a critical hallmark of glioma, and significantly compromises treatment
efficacy. Unfortunately, techniques for monitoring glioma pO2 to facilitate
translational research are lacking. Furthermore, poor prognosis of patients with
malignant glioma, in particular glioblastoma multiforme, warrant effective
strategies that can inhibit hypoxia and improve treatment outcome. EPR oximetry
using implantable resonators was implemented for monitoring pO2 in normal
cerebral tissue and U251 glioma in mice. Breathing carbogen (95% O2 + 5% CO2 )
was tested for hyperoxia in the normal brain and glioma xenografts. A new
strategy to inhibit glioma growth by rationally combining gemcitabine and MK
8776, a cell cycle checkpoint inhibitor, was also investigated. The mean pO2 of
left and right hemisphere were ~56-69 mmHg in the normal cerebral tissue of mice.
The mean baseline pO2 of U251 glioma on the first and fifth day of measurement
was 21.9 +/- 3.7 and 14.1 +/- 2.4 mmHg, respectively. The mean brain pO2
including glioma increased by at least 100% on carbogen inhalation, although the
response varied between the animals over days. Treatment with gemcitabine + MK
8776 significantly increased pO2 and inhibited glioma growth assessed by MRI. In
conclusion, EPR oximetry with implantable resonators can be used to monitor the
efficacy of carbogen inhalation and chemotherapy on orthotopic glioma in mice.
The increase in glioma pO2 of mice breathing carbogen can be used to improve
treatment outcome. The treatment with gemcitabine + MK-8776 is a promising
strategy that warrants further investigation.
PMID- 25111973
TI - "Everybody's plastic": so what?
PMID- 25111974
TI - Prenatal melamine exposure induces impairments of spatial cognition and
hippocampal synaptic plasticity in male adolescent rats.
AB - Our previous studies showed that chronic melamine exposure could affect
hippocampal synaptic plasticity and impair learning and memory on adult rats. In
this study, we investigated whether prenatal melamine exposure (PME) induced
cognitive deficits and impairment of synaptic plasticity in postnatal offspring.
An animal model was produced by melamine exposure throughout gestational period
with 400mg/kg/day, while male offspring rats were employed. Rats' performance in
Morris water maze (MWM) was tested to evaluate learning and memory. To examine
the variations of paired-pulse facilitation (PPF) and synaptic plasticity, field
excitatory postsynaptic potentials (fEPSPs) were recorded in hippocampal CA1 by
stimulating Schaffer collaterals path. The result showed that PME probably
impaired spatial learning and memory. The fEPSPs amplitudes of LTP were much
lower and the PPF ratio was significantly higher in PME group than controls.
These data suggested that PME impaired hippocampal synaptic function, which was
partly involved in spatial cognition impairments.
PMID- 25111976
TI - Effect of extended pi-conjugation structure of donor-acceptor conjugated
copolymers on the photoelectronic properties.
AB - New donor-acceptor conjugated copolymers based on alkylthienylbenzodithiophene
(BDTT) and alkoxynaphthodithiophene (NDT) have been synthesized and compared with
their benzo[1,2-b:4,5-b']dithiophene (BDT)-based analogues to investigate the
effect of the extended pi conjugation of the polymer main chain on the
physicochemical properties of the polymers. A systematic investigation into the
optical properties, energy levels, field-effect transistor characteristics, and
photovoltaic characteristics of these polymers was conducted. Both polymers
demonstrated enhanced photovoltaic performance and increased hole mobility
compared with the BDT-based analogue. However, the BDTT-based polymer (with pi
conjugation extension perpendicular to main chain) gave the highest power
conversion efficiency of 5.07% for the single-junction polymer solar cell,
whereas the NDT-based polymer (with pi-conjugation extension along the main
chain) achieved the highest hole mobility of approximately 0.1 cm(2) V(-1) s(-1)
based on the field-effect transistor; this indicated that extending the pi
conjugation in different orientations would have a significant influence on the
properties of the resulting polymers.
PMID- 25111975
TI - Zebrafish embryotoxicity test for developmental (neuro)toxicity: Demo case of an
integrated screening approach system using anti-epileptic drugs.
AB - To improve the predictability of the zebrafish embryotoxicity test (ZET) for
developmental (neuro)toxicity screening, we used a multiple-endpoints strategy,
including morphology, motor activity (MA), histopathology and kinetics. The model
compounds used were antiepileptic drugs (AEDs): valproic acid (VPA),
carbamazepine (CBZ), ethosuximide (ETH) and levetiracetam (LEV). For VPA,
histopathology was the most sensitive parameter, showing effects already at
60MUM. For CBZ, morphology and MA were the most sensitive parameters, showing
effects at 180MUM. For ETH, all endpoints showed similar sensitivity (6.6mM),
whereas MA was the most sensitive parameter for LEV (40mM). Inclusion of kinetics
did not alter the absolute ranking of the compounds, but the relative potency was
changed considerably. Taking all together, this demo-case study showed that
inclusion of multiple-endpoints in ZET may increase the sensitivity of the assay,
contribute to the elucidation of the mode of toxic action and to a better
definition of the applicability domain of ZET.
PMID- 25111977
TI - Behavioral side effects of pediatric acute lymphoblastic leukemia treatment: the
role of parenting strategies.
AB - BACKGROUND: Behavioral and emotional difficulties are a recognised side effect of
childhood acute lymphoblastic leukemia (ALL) treatment. Modifiable factors, such
as parenting strategies, may be an appropriate target for interventions to assist
families with managing their child's behavior, potentially leading to improved
psychosocial and clinical outcomes. This study examined whether parenting
strategies are associated with child behavioral and emotional problems in a
pediatric oncology context, with the aim of establishing whether parenting is a
potential modifiable target for psychosocial intervention. PROCEDURE:
Participants included 73 parents of children aged 2-6 years who were either (i)
in the maintenance phase of treatment for ALL at the Royal Children's Hospital
Children's Cancer Centre, Melbourne (N = 43), or (ii) had no major medical
history (healthy control group) (N = 30). Participants completed psychometrically
validated questionnaires that assessed parenting strategies and child emotional
and behavioral problems. RESULTS: Results revealed that the ALL group parents
reported higher lax parenting and more spoiling and bribing of their child than
the healthy control group. Results from regression models indicated that, after
controlling for the significant contribution of illness status and child age on
child emotional and behavioral difficulties, parental laxness and parental
overprotection were significantly associated with child emotional and behavioral
difficulties. CONCLUSIONS: Supporting parents to minimise sub-optimal parenting
strategies, particularly lax parenting, may offer a fruitful avenue for future
research directed toward modifiable factors associated with managing child
emotional and behavioral problems in a pediatric oncology context.
PMID- 25111978
TI - Reduction of physiological effects in fNIRS waveforms for efficient brain-state
decoding.
AB - This paper presents a methodology for online estimation of brain activities with
reduction in the effects of physiological noises in functional near-infrared
spectroscopy signals. The input-output characteristics of a hemodynamic response
are modeled as an autoregressive moving average model together with exogenous
physical signals (i.e., ARMAX). In contrast to the fixed design matrix in the
conventional general linear model, the proposed model incorporates the temporal
variations in the experimental paradigm as well as in the hemodynamics. The
performance of the proposed method has been tested by using box-car type
functions followed by individual tapping tasks. The results and their
significance were verified using t-statistics indicating that ARMAX seems to be
better able to track/reveal the hemodynamic response. Also, online brain
activation maps were generated for localizing brain activities. Experimental
results are compared with those of the existing conventional GLM-based method.
PMID- 25111979
TI - alpha-Synuclein rs356219 polymorphisms in patients with Gaucher disease and
Parkinson disease.
AB - Mutations in beta-glucocerebrosidase, the genetic defect in Gaucher disease (GD),
are an important susceptibility factor for Parkinson disease (PD). A PD effector
is alpha-synuclein (SNCA) hypothesized to selectively interact with beta
glucocerebrosidase under lysosomal conditions. SNCA polymorphism rs356219 may be
associated with early-age-onset PD, common among patients with GD+PD. The
objective of this study was to ascertain rs356219 genotypes of GD+PD patients.
All GD+PD patients at our Gaucher referral clinic were asked to participate. A GD
only sex-, age-, GD genotype-, and enzyme therapy (ERT)-matched control was found
for each GD+PD participant. Student's t-test was used (p-value <0.05 as
significant). There were 14 GD+PD patients: all Ashkenazi Jewish; 11 males
(78.6%); mean (range) age diagnosed GD 34.2 (5-62) years; 50% N370S homozygous;
mild to moderate GD; 3 asplenic and only these have osteonecrosis; 5 received
ERT; mean age (range) diagnosed PD was 57.8 (43-70) years; first PD sign was
tremor in 9 (64.3%); cognitive dysfunction in all. In GD+PD, frequency for AG+GG
(9) was greater than AA (5); in GD only, there was equality (7). Odds Ratio risk
for PD increases with number minor alleles: but not significantly greater among
GD+PD than GD only; in aggregate, there was no difference between cohorts for
frequency of minor alleles. The limitation of this study is few GD+PD, albeit
virtually all the GD+PD cohort >500 adult GD patients in our clinic. Nonetheless,
as a foray into potential genetic GD susceptibility for a synucleinopathy, this
study suggests the need for collaboration to achieve larger sample size.
PMID- 25111980
TI - Feto-maternal allo-immunity, regulatory T cells and predisposition to auto
immunity. Does it all start in utero?
AB - During gestation, maternal cells traffic to the fetus leading to the natural
phenomenon of microchimerism. Although their persistence in offspring has been
associated with several autoimmune disorders, the precise role of maternal cells
in these disorders remains unclear. We aimed to evaluate whether alloreactive
maternal T cells could directly trigger a graft-vs.-host like reaction or
indirectly influence the development of the offspring's regulatory T cells (Treg)
favoring autoimmunity. In a specific breeding strategy, we recently reported that
maternal allogeneic T cells changed fetal Treg development and their quantities
in mesenteric lymph nodes, leading to early signs of inflammation in the gut
later in life. Although maternal microchimeric T cells were found in newborn
tissues, we could not detect any cells in the gut from adult offspring where the
inflammation occurred. Thus, strongly alloreactive maternal microchimeric T cells
may indirectly drive the offspring to gut inflammation. We believe these results
suggest a new mechanism for predisposition to auto-immunity.
PMID- 25111981
TI - Diagnostic usefulness of quantitative tissue velocity imaging and anatomic M-mode
echocardiography for coronary artery diseases: A pilot study.
AB - BACKGROUND AND OBJECTIVE: To explore the potential clinical usefulness and
determine optimal diagnostic criteria of quantitative tissue velocity imaging and
anatomic M-mode echocardiography in patients with coronary artery disease (CAD).
METHODS: We used quantitative tissue velocity imaging for the measurement of
systolic myocardial velocity, and anatomic M-mode echocardiography for the
measurement of ventricular wall-thickening fraction in 44 subjects with suspected
CAD. Subjects were classified as patients if coronary angiography demonstrated a
stenosis >= 50%, and as controls if it was strictly normal. The diagnostic
criteria, sensitivity, and specificity were assessed by receiver-operator curves.
RESULTS: Controls had greater mean systolic myocardial velocity and ventricular
wall-thickening fraction in the basal (6.59 +/- 1.25 cm/s and 0.44 +/- 0.05) and
mid segment (5.23 +/- 0.93 cm/s and 0.43 +/- 0.04) than patients (5.02 +/- 1.17
cm/s and 0.29 +/- 0.04, 3.27 +/- 1.29 cm/s and 0.29 +/- 0.04, respectively, p <
0.001). Mid-segment ventricular wall-thickening fraction offered 95% sensitivity
(95% CI 88.7% to 98.4%), and 98.3% specificity (95% CI 90.9% to 1.0) with an
optimal cut-off point of 0.349, yielding better results than systolic myocardial
velocity, which provided 83% sensitivity (95% CI 74.2% to 89.8%), 90% specificity
(95% CI 79.5% to 96.2%), and optimal cut-off point 4.47. The combination of
systolic myocardial velocity and ventricular wall-thickening fraction offered 97%
sensitivity (95% CI 91.5% to 99.4%) CONCLUSIONS: Mid-segment ventricular wall
thickening fraction might be suitable for the evaluation of patients with CAD.
PMID- 25111982
TI - Coronary artery disease and 10-year outcome after hospital admission for heart
failure with preserved and with reduced ejection fraction.
AB - AIMS: The prognostic impact of coronary artery disease (CAD) in heart failure is
debated. Whereas causes of death have been well described in patients with
cardiomyopathy, little is known about how CAD influences causes of death in heart
failure with preserved ejection fraction (HFPEF). We undertook a 10-year study
and analysed causes of death in relation with CAD in HFPEF and in heart failure
with reduced ejection fraction (HFREF). METHODS AND RESULTS: Our prospective
analysis included 591 consecutive patients (320 HFPEF and 271 HFREF) hospitalized
for the first time for heart failure during 2000 and followed for 10 years.
History of CAD was documented in 25% of HFPEF and 39% of HFREF patients (P <
0.001). Overall, CAD was independently predictive of all-cause and cardiovascular
death. CAD had powerful prognostic impact in HFREF [adjusted hazard ratio (HR)
1.60 (1.19-2.15) for all-cause death, and adjusted HR 2.01 (1.38-2.92) for
cardiovascular death]. In HFPEF, the association between CAD and cardiovascular
death was no longer observed after adjustment [adjusted HR 1.01 (0.69-1.50)]. In
HFREF, CAD was associated with increased risk of heart failure-related (adjusted
HR 2.03 (1.21-3.43)] and myocardial infarction-related fatal events [adjusted HR
3.84 (1.16-12.7)], while HFPEF patients with CAD appeared at greater risk of
sudden death [adjusted HR 2.22 (1.05-4.95)]. CONCLUSION: The prognostic impact of
CAD is different in HFPEF compared with HFREF. Patients with HFPEF and CAD are at
high risk of cardiovascular death, especially sudden death.
PMID- 25111983
TI - Cancer germline gene activation: friend or foe?
PMID- 25111985
TI - Retracted manuscript: Barre B, et al. Cell Cycle 2010; 9:4795-804.
PMID- 25111986
TI - Special issue "Organ replacement approaches".
PMID- 25111988
TI - Tips for finding reliable health information online.
PMID- 25111987
TI - Assessment of factors affecting the difficulty of caudal epidural injections in
adults using ultrasound.
AB - BACKGROUND: In unaided caudal epidural block (CEB), incorrect needle insertion
has been reported to occur in 15% to 38% of attempts. OBJECTIVE: To statistically
analyze the anatomical variables affecting difficult CEB using ultrasonographic
measurement. METHODS: Preprocedural ultrasonography was performed and the
following measurements were obtained in 146 patients: the distance from the skin
to the apex of the sacral hiatus; the depth of the sacral canal at the apex of
the sacral hiatus; the length of the sacrococcygeal ligament between the apex of
the sacral hiatus and sacral base; the distance from the skin to the apex of the
sacral cornu; and the distance between the apexes of bilateral cornua. One
clinician, unaware of the ultrasonographic findings, performed the injections
using the landmark technique. The procedures were videotaped and were
subsequently reviewed by an independent investigator. RESULTS: The means (+/-
SDs) of the abovementioned measurements were 12.1+/-3.7 mm, 6.1+/-2.1 mm, 25.9+/
7.4 mm, 10.0+/-4.0 mm and 16.4+/-3.2 mm, respectively. Injections failed in 16
(11%) patients and were defined as difficult in 21 (14.4%) patients. The depth of
the sacral canal at the apex of sacral hiatus (P<0.001) and the length of the
sacrococcygeal ligament between the apex of the sacral hiatus and sacral base
(P=0.001) were significant predictors of difficult CEB. Of all patients, 85.7%
and 75.2% were correctly classified as difficult or not difficult, respectively.
The cutoff values of the depth of the sacral canal at the apex of the sacral
hiatus and the length of the sacrococcygeal ligament between the apex of the
sacral hiatus and the sacral base to predict a difficult CEB were 3.7 mm and 17.6
mm, respectively. CONCLUSIONS: Both the depth of the sacral canal at the apex of
the sacral hiatus and the length of the sacrococcygeal ligament between the apex
of the sacral hiatus and sacral base are significant variables affecting the
difficulty of the CEB.
PMID- 25111990
TI - NIH-funded study finding: investigational oral regimen for hepatitis C shows
promise.
PMID- 25111989
TI - Obesity programs for children may help lower blood pressure.
PMID- 25111991
TI - The NIH urges older Americans to protect their kidneys.
PMID- 25111992
TI - Nurse staffing and education linked to reduced patient mortality.
PMID- 25111994
TI - Abstracts of the 16th International Conference for Philosophy, Psychiatry and
Psychology, June 26-29, 2014, Bulgaria.
PMID- 25111993
TI - NIH-funded study finding: data supports benefits of colon cancer screening.
PMID- 25111995
TI - Radio-guided parathyroidectomy for secondary hyperparathyroidism.
AB - BACKGROUND: The value of gamma probes in the surgical treatment of secondary
hyperparathyroidism (sHPT) was determined. METHOD: We retrospectively analyzed
the clinical data of 48 sHPT patients between May 2007 and September 2011.
Preoperative (99)Tc(m)- methoxyisobutyl isonitrile (MIBI) scintigraphy and high
frequency ultrasonography were used for parathyroid localization. Thirty-five
patients (group I) underwent conventional neck exploration and open
parathyroidectomy. Thirteen patients (group II) underwent gamma probe-guided
total parathyroidectomy and parathyroid transplantation. The two groups were
compared in terms of the number of parathyroid resections, operative time, and
postoperative changes in the blood levels of parathyroid hormone (PTH), calcium,
and phosphate. RESULTS: The clinical manifestations, PTH and calcium levels, age
distribution, and clinical characteristics did not differ between the two groups.
The accuracy of preoperative (99)Tc(m)-MIBI scintigraphy (89.74%) for the
diagnosis of hyperparathyroidism did not differ from that of ultrasonography
(81.25%). However, the accuracy of (99)Tc(m)-MIBI scintigraphy (66.67%) for
localizing hyperfunctioning parathyroids was significantly lower than that of
ultrasonography (76.86%). The operation time was significantly longer in group I
(120+/-25) min than in group II (90+/-30) min. The accuracy of parathyroid
specimens were obtained in group I (2.5+/-0.5) than in group II (3.5+/-0.5).
Compared with group I, group II showed a significant increase (15.4%) in the
number of parathyroid resections. The PTH, calcium, and phosphate levels
significantly decreased postoperatively in all patients. CONCLUSION:
Intraoperative gamma probe examination confirmed that the excised specimen was
parathyroid tissue and improved the accuracy of parathyroid resection. The
parathyroidectomy rate was increased by 15.4% due to the use of these probes.
However, the probes did not detect all ectopic parathyroids, and further research
is required to clarify the underlying reasons.
PMID- 25111996
TI - When you need medical care, stat.
PMID- 25111998
TI - Fix mistakes on your medical bill.
PMID- 25111999
TI - How to pick a medical alert system.
PMID- 25111997
TI - Where should you go for heart surgery? Our new ratings of more than 400 hospitals
can help you find the right one.
PMID- 25112000
TI - Deadly pain pills: everyday, 46 people in the U.S. die from legal pain pills.
Here's how to avoid being a statistic.
PMID- 25112002
TI - [How do we treat an electrical storm in implantable cardioverter defibrillator
(ICD) appropriate patients?].
PMID- 25112001
TI - Reanalyzing reverse payment settlements: a solution to the patentee's dilemma.
PMID- 25112003
TI - [Reconstruction of full-thickness nasal alar defect with combined nasolabial flap
and free auricular composite flap].
AB - OBJECTIVE: To investigate the technique and its effect of combined nasolabial
flap and free auricular composite flap for full-thickness nasal alar defect.
METHODS: From March 2010 to March 2013, 9 patients with full-thickness nasal alar
defects were treated with combined nasolabial flaps and free auricular composite
flaps. Composite auricular flap was used as inner lining and cartilage framework.
The nasolabial flap at the same side was used as outer lining. RESULTS: All the
patients were followed up for 6-18 months (average, 12 months). All the 9
composite auricular flaps survived completely. Epidermal necrosis happened at the
distal end of 1 nasolabial flap. Alar rim was almost normal and symmetric nose
was achieved in 6 cases. The arc and the thickness of the alar rim was not enough
in 3 cases, resulting in asymmetric appearance. CONCLUSIONS: The survival area of
auricular composite flap can be enlarged with nasolabial flap. The auricular
helix edge can be reserved to reconstruct nasal alar rim with smooth and natural
arc. Large full-thickness nasal alar defedts can be reconstructed with combined
nasolabial flaps and free auricular composite flaps.
PMID- 25112004
TI - [Comparative study in reconstruction of tongue defect with thin anterolateral
flap and forearm flap].
AB - OBJECTIVE: To compare the thin anterolateral flap with forearm flap in tongue
defect repairing, and to introduce our methods and experiences in the tongue
reconstruction with the thin anterolateral flap. METHODS: The clinicopathologic
data of 46 cases with tongue carcinoma were obtained from School of Stomatology,
Nanjing University Medical Center, Nanjing University from December 2009 to
December 2011. To compare two methods of incidence of vascular crisis, tongue
shape, language and swallowing functional recovery. RESULTS: 46 patients with
tongue carcinoma were performed the tongue reconstruction in 12 month, which 12
cases were used the thin anterolateral flap and 34 cases were used the forearm
flap. In the thin anterolateral flap group, All cases were succeeded. 1 case
occurs vascular crisis. In the forearm flap group, 33 cases were succeeded, and 1
case occurs necrosis. 3 cases occurs vascular crisis. The results of comparing
two methods showed that: no obvious differences in the tongue shape, and no
obvious differences in the function of language and swallowing. CONCLUSIONS:
There no obvious differences in the reconstruction of tongue defect between the
thin anterolateral flap and the forearm flap. The thin anterolateral flap have
some advantages: little influence is on the donor site, the flap extent is
abundant, the donor site is not spectacular. The thin anterolateral flap should
be piror method for the tongue defect repairing.
PMID- 25112005
TI - [Application of the expanded distant skin flaps for the facial and cervical
deformities].
AB - OBJECTIVE: To investigate the application of expanded distant skin flaps for the
facial and cervical deformities. METHODS: 96 patients with facial and cervical
deformities who underwent reconstructive surgery with expanded distant skin flaps
were retrospectively reviewed and followed up. RESULTS: Good results were
achieved in 95 cases. Necrosis happened in the distal end of one flap. The
patients were followed up for 1-8 years with good cosmetic results, such as well
matched flap texture and color. CONCLUSION: The expanded distant skin flap is
suitable and reliable for facial and cervical deformities.
PMID- 25112006
TI - [Primary report of single rib-cartilage recombination transplantation in Binder
syndrome treatment].
AB - OBJECTIVE: To explore the surgical methods and advantages of single rib-cartilage
recombination transplantation in Binder syndrome treatment. METHODS: Five
patients were treated with single rib-cartilage recombination transplantation. We
harvested only the seventh costal cartilage including partial costal bone of the
same rib to correct all the deformities. The rib was divided into 3 parts: 1 I
shaped cartilage, 1 inverted-T-shaped cartilage, and 1 C-shaped implant (later
divided into a C and a reversed-C implant) composed of rib bone and cartilage.
The first 2 parts were constructed to an L-shaped implant for nasal dorsum
augmentation, collumella support, and nasal base elevation. The C-shaped and
reversed-C-shaped implants were placed on both sides of the pyriform aperture.
RESULTS: All patients were followed up for eighteen to thirty months. No apparent
deviation on the nasal support was found. CONCLUSION: Single rib-cartilage
recombination transplantation in Binder syndrome treatment has lots of
advantages, such as less morbidity, rapid recovery, and good results.
PMID- 25112007
TI - [Correction of minor breast ptosis by subfascia breast augmentation with
periareolar incision and anatomic mammary implant].
AB - OBJECTIVE: To correct the minor breast ptosis with minimal breast scar. METHODS:
32 cases with minor breast ptosis were corrected by subfascia breast augmentation
with periareolar incision and anatomic mammary implant. RESULT: Breast ptosis was
completely or mostly corrected in all the patitents with periareola scar,
avoiding the vertical breast scar. Except for short-time effusion in 2 cases, no
other complication happened. CONCLUSIONS: Subfascia breast augmentation with
periareolar incision and anatomic mammary implant can effectively correct minor
breast ptosis with minimal breast scar and less complication.
PMID- 25112008
TI - [Comparative study of three different methods for penile reconstruction].
AB - OBJECTIVE: To compare the effect of three methods for penile reconstruction.
METHODS: From Sept. 2000 to Dec. 2012, penile reconstruction was performed in 48
cases with free scapular flap transplantation, or pedicled superficial circumflex
iliac artery skin flap, or anterolateral thigh skin flap pedicled with lateral
circumflex femoral artery. The flaps were 12.0-14.5 cm in length, 10-12 cm in
width and the urethra perimeter was about 2-3 cm. RESULTS: Free scapular flaps
were used in 21 cases, with flap failure in 3 cases due to insufficient blood
supply. Malleable penile prosthesis was implanted in 11 cases, which was exposed
in 3 cases. Groin skin flaps were used in 21 cases, with flap failure in 8 cases
due to insufficient blood supply. Malleable penile prostheses were implanted in 7
cases, which was exposed in 3 cases. Anterolateral thigh skin flaps were used in
6 cases, with flap failure in 2 cases due to necrosis and infection. No
prosthesis was implanted in this group. All the failure cases underwent secondary
reconstruction with successful results. 37 cases were followed up for 1-6 years,
avevage 2.5 years. 26 cases were satisfied with the results of appearance and
function. CONCLUSIONS: Among these three methods, the free scapular flap is most
recommended for its high survival rate, low complication rate and high patient
satisfaction.
PMID- 25112009
TI - [Efficacy of dexmedetomidine combined with remifentanil for lower eyelid
blepharoplasty].
AB - OBJECTIVE: To explore the feasibility and safety of dexmedetomidine combined with
remifentanil for lower eyelid blepharoplasty. METHODS: 50 patients undergoing
lower eyelid blepharoplasty ASA I - II were randomly divided into 2 groups (25 in
each group) as observation group and control group. Dexmedetomidine (0.3 microg x
kg(-1) x h(-1)) and remifentanil (0.05 microg x kg(-1) x min(-1)) were used in
observation group. Local anesthesia by lidocaine (1%) combined with midazolam
(0.04 mg/kg) intravenous sedation were used in control group. HR, mean arterial
pressure (MAP), heart rate (HR), breathing rate (RR), pulse oxygen saturation
(SpO2) change were monitored and recorded before and after the administration of
the drug, as well as at the beginning of operation, during the operation, at the
end of the operation, and 5 minutes after the operation. Patients sedation degree
was evaluated by Ramsay. Operation time, recovery time, the incidence of adverse
reactions, the satisfaction of patients and doctors were also recorded. RESULTS:
Patients had no obvious difference of intraoperative MAP, RR, SpO2, operation
time and postoperative recovery time between the two groups (P > 0.05). Compared
with control group, HR during the operation were decreased significantly [(64.2
+/- 8.2) bpm, P < 0.05] in observation group. In control group, there were 18
cases of patients with agitation, but they endured the operation anyway. In
observation group, 24 cases of patients underwent operation without agitation.
The satisfaction of patients and the operation doctors (96%) in observation group
were markedly higher than that in control group (P < 0.05). CONCLUSION:
Dexmedetomidine combined with remifentanil is practical and safe. The effect of
reducing HR should be noticed.
PMID- 25112010
TI - [Effect of postoperative analgesia with dexmedetomidine on the survival rate of
amputated finger replantation].
AB - OBJECTIVE: To observe the effect of postoperative analgesia with dexmedetomidine
on the survival rate of amputated finger replantation. METHODS: 91 cases, who was
going to receive amputated finger replantation, were randomly divided into group
A (n = 48) and B (n = 43). PCIA (patient-controlled intravenous analgesia) was
set immediately after operation in group A (fentanyl 1.0 mg + tropisetron 4.0 mg
+ 10 mg + dexmedetomidine 200 microg + saline 100 ml) and group B (same as group
A except dexmedetomidine). Background infusion is 2 ml/h with a bolous of 0.5 ml
and lockout time is 15 min. postoperative VAS score, Ramsay score, condition of
replanted fingers and other adverse events at the 0-6 h, 6-12 h, 12-24 h and 24
48 h were recorded and analyzed. RESULTS: The age, sex, height, weight, amputated
time (Ts), revascularized time (Tt) in the two groups were not statistically
different (P > 0.05). Postoperative VAS score in the two groups was significantly
different at the 0-6 h, 6-12 h, 12-24 h and 24-48 h (P < 0.05), but Ramsay score
was not (P > 0.05). The highest and lowest postoperative VAS score and Ramsay
score were markedly different between two groups (P < 0.05). 3 of the 60 fingers
in group A experienced vascular crisis and 2 underwent vascular explore surgery.
13 of 56 fingers in group B occurred vascular crisis, and 10 underwent vascular
explore surgery, showing significant difference between the two groups (P <
0.05). PCIA adverse reactions showed no difference between the two groups (P >
0.05). Bradycardia and hypotension didn't happen in any patients in the two
groups. 4 weeks after surgery, the survival rate was 96.7% (58/60) in group A,
and 83.9% (47/56) in group B (P < 0.05). CONCLUSION: Postoperative analgesia with
dexmedetomidine as an adjuvant can increase the survival rate of replantation
fingers with high safety.
PMID- 25112011
TI - [Functions of retinoic acid on the biological characteristics of human embryonic
stem cells].
AB - OBJECTIVE: To analyze the influence of retinoic acid (RA) on the undifferentiated
state and EB formation abilities of human embryonic stem cells. METHODS: The
biological characteristics of H9 ESCs after RA treatment were characterized by
real-time PCR, MTS proliferation assay and immunofluorescence staining. The
expression of three germ layers markers, osteogenic differentiation markers and
adipogenic differentiation markers in H9-differentiated embryoid bodies (EBs)
with RA treatment were quantified by real time PCR. RESULTS: The proliferation of
H9 ESCs in the early logarithmic growth phase was accelerated by RA treatment. In
addition, RA induced differentiation of H9 ESC coupled with morphology changes,
decreased expression of undifferentiated markers Oct4, Nanog, Sox2 and OCT4 mRNA
binding protein Lin28 at mRNA level, and reduced expression of Oct4 at protein
level. RA induced formation of cavities in EBs. Real time PCR results showed that
the expressions of ectodermal markers: NeuroD1, Noggin; mesodermal markers:
Brachyury, Twist and endodermal markers: AFP, GATA-4 were significantly increased
(P < 0.05), especially for AFP (P < 0.01), by RA treatment in a dose-dependent
manner. In addition, the expression of adipogenic differentiation marker
C/EBPalpha was increased while the osteogenic differentiation marker OPN was
decreased in EBs after RA treatment for 5 days. CONCLUSIONS: High concentrations
of RA induced the loss of stemness in H9 ESCs and excessive differentiation in
EBs, and damaged the balance between osteogenic and adipogenic differentiation
during early EB differentiation, which may be relevant to the congenital
malformations.
PMID- 25112012
TI - [The expressions of notch genes in human keloid-derived mesenchymal-like stem
cells].
AB - OBJECTIVE: To study the expressions of Notch1-4 gene in human keloid-derived
mesenchymal-like stem cells, and to explore the Notch signaling pathway's role in
the formation of keloid. METHODS: Keloid samples were collected to harvest human
keloid-derived mesenchymal-like stem cells through two-step enzymatic
dissociation method. By flow cytometry, cell phenotype of primary and P3
generation were analyzed. By immunocytochemistry, the expressions of Oct4,
vimentin and CK19 were examined. Keloid-derived mesenchymal-like stem cells were
induced into osteoblasts in vitro and calcium deposition was detected by Alizarin
red S stain. Realtime polymerase chain reaction (RT-PCR) was used to detect the
expressions of Notch1-4 mRNA in keloid-derived mesenchymal-like stem cells.
RESULTS: Flow cytometry showed that keloid-derived mesenchymal-like stem cells of
primary and P3 generation highly expressed CD29, CD44, CD90 from the typical MSC
phenotype marker, but they failed to express HSC phenotype markers, such as CD34
and CD45. The results of immunocytochemistry showed that Oct4 from pluripotent
stem cell markers and vimentin from mesenchymal cell markers was positive and
CK19 from epithelial cell markers was negative. After induced differentiation
into osteoblasts in vitro after 21 day, calcium nodules could be seen clearly;
Notch1-4 gene were expressed in keloid-derived mesenchymal-like stem cells
through RT-PCR. The relative quantitative of Notch2, Notch3 gene were higher than
Notch1, Notch4 gene (P < 0.05). CONCLUSIONS: The expression difference of
different subtypes from Notch gene in human keloid-derived mesenchymal-like stem
ceils may be related to self-renewal, proliferation, differentiation, and
participate in the formation of keloid.
PMID- 25112013
TI - [Preliminary study of the biological characteristics of fibroblasts in human
granulation tissue in vitro].
AB - OBJECTIVE: To explore the biological characteristics of fibroblasts in adult
granulation tissue in vitro, including cell viability, CD phenotypic, factor and
protein expression, and differentiation, so as to facilitate further research of
the role of fibroblasts in early wound healing. METHODS: Fibroblasts were
isolated from human granulation tissue and cultured by mechanical and enzymatic
digestion method. The cell morphology and proliferation were observed under
inverted phase contrast microscope. The first and third passages of cells' growth
curve were drawn respectively. The surface markers (CD105, CD73, CD90, CD44,
CD34, CD45, CD19, CD11b, HLA-DR) of the first and third passage fibroblasts were
identified by Flow Cytometry. And the expression of Vimentin, CK19, CD31 and
Factor VIII were detected by immunocytochemistry. RESULTS: Primary cultured
fibroblasts were short spindle, polygonal and irregular in shape. The morphology
of fibroblasts were uniform by repeatedly passage cultured in vitro and showed
spindle-shaped. The proliferative capacity of the fibroblasts were not
significantly different, with logarithmic growth phase. From 1 to 4 days, The
primary and third passage cells' proliferation was no difference (P > 0.05),
After the five days, the proliferative ability of third generation was better
than the primary passage (P < 0.01). All fibroblasts highly expressed mesenchymal
stem cells' surface markers CD105, CD73, CD90 and CD44, and didnt express
hematopoietic stem cells' surface markers CD34, CD45, CD19, CD11b and HLA-DR. The
expression of mesenchymal stem cells' surface markers in third generation of
cells were increased significantly. Immunocytochemistry showed positive
expression of Vimentin, CD31, and negative expression of CK19 and Factor VIII.
CONCLUSIONS: Fibroblasts in human granulation tissue show the biology
characteristics of Mesenchymal Stem Cells. Some biological markers of endothelial
cells are expressed in fibroblasts in granulation tissue. The fibroblasts may
play an important role during the process of endothelial to mesenchymal
transformation in early wound healing.
PMID- 25112014
TI - [In vitro induction of human breast adipose-derived stem cells into epithelial
like cells by co-culturing].
AB - OBJECTIVE: To explore the feasibility of the transdiferentiation of human breast
adipose-derived stem cells (hbASCs) into mammary epithelial-like cells after co
culturing in Transwell in vitro. METHODS: The third passage hbASC and the HBL-100
cell line were co-cultured in a Transwell culture system for 15 days. The hbASCs
were observed and identified by inverted phase contrast microscope and
transmission electron microscopy, and immunocytochemistry staining in the induced
and control groups. RESULTS: Both the third passage hbASCs and the HBL-100 cell
line cells could adhere and grow rapidly after co-culture in the Transwell
system. After co-culture for 15 days, the morphology of some induced hbASCs
changed into epithelial-like cells. Some induced hbASCs showed positive
expression of CK18, CK19 by immunocytochemistry staining, and typical epithelium
cells with microvilli, desmosomes and tonofilaments observed under TEM. The
positive rate of CK18 and CK19 was (24.4 +/- 12.0)% and (21.6 +/- 16.4)% in
experimental group, and (1.8 +/- 1.7)% and (1.1 +/- 0.6)% in control group.
CONCLUSION: The data suggests that hbASCs may have the potential to
transdifferentiate into human mammary epithelial-like cells after co-culturing in
Transwell in vitro.
PMID- 25112016
TI - Responding to the peer review.
PMID- 25112015
TI - [Vascular supply of intrinsic muscles of foot and anatomic basis for muscular
flaps design].
AB - OBJECTIVE: To investigate the vascular supply of intrinsic muscles of foot and
anatomic basis for muscular flap design. METHODS: A radiopaque injectate (lead
oxide-gelatin mixtures, 26 ml/kg) was injected into 10 fresh cadavers. The
dissected regions were photographed and each intrinsic muscles on the foot was
removed and radiographed. The number, type, diameter of vascular branches of
muscles and their distributions were observed. The area of the vascular territory
supplied by each source vessel was calculated using Scion Image for Windows
software. RESULTS: There were significant architectural differences among the
intrinsic muscles. The muscles length varied from 22.5mm to 116.2mm [average,
(66.1 +/- 23.2)mm]. The measured fiber length were relatively consistent, ranging
from 14.2 mm to 27.5 mm [average, (20.2 +/- 4.5)mm]. There are 63 vascular
branches into the 23 foot muscles, each muscle having average branches of 3.2 +/-
0.8. The average diameter of branches, the length and width of each vascular
territorial area is (0.8 +/- 0.3) mm, (2.2 +/- 0.8) cm, and (0.9 +/- 0.4) cm,
respectively. Other findings included that some muscles were not present in some
cadavers. CONCLUSIONS: The blood supply of intrinsic muscles of foot is abundant
with different diameter and distributions of branches. There is an anatomic basis
for muscular or musculoosseous flap design. There are 7 intrinsic muscles with
large and reliable vascular supply which can be chosen as muscular flaps.
PMID- 25112017
TI - Preparing quality improvement, research, and evidence-based practice manuscripts.
PMID- 25112018
TI - Evaluation of the effect of cranberry juice on symptoms associated with a urinary
tract infection.
AB - The purpose of this research was to correlate daily consumption of cranberry
juice and symptoms of a diagnosed UTI among 26 volunteer adult female patients.
PMID- 25112019
TI - The effect of collection method on urinalysis results in women with pelvic organ
prolapse.
AB - Midstream clean catch and catheterized urine specimens were obtained for each
patient and samples were compared by microscopic urinalysis. The results of this
study demonstrate that a midstream clean catch does not yield accurate urinalysis
results in women with advanced urogenital prolapse.
PMID- 25112020
TI - Adding to the evidence base: the effect of collection method on urinalysis in
women with pelvic organ prolapse.
PMID- 25112021
TI - A nurse practitioner's experience in a post-graduate nurse practitioner urology
fellowship.
AB - In 2012 the Division of Urologic Surgery at Washington University School of
Medicine developed and piloted a 12-month post-graduate nurse practitioner
fellowship. The author completed this fellowship. This is a report on the
experiences.
PMID- 25112022
TI - Monolateral purple urine bag syndrome in a patient with bilateral nephrostomy
tubes.
AB - Purple urine bag syndrome (PUBS) is a constellation of findings resulting in
purple discoloration of the urine and/or urine drainage bag(s) occurring in
patients with long-term urinary indwelling catheters. Other causative factors may
include constipation, female gender, the presence of bacteria containing
sulphatase and phosphatase enzymes, and alkaline urine. While the contributing
factors for PUBS are linked with high morbidity, PUBS itself is a benign
condition. A case study of monolateral PUBS in a patient with bilateral
nephrostomy tubes (NTs) is presented.
PMID- 25112023
TI - Conservative management of acute scrotal edema.
AB - Scrotal edema is a prevalent issue. It is difficult to treat and has a myriad of
causes. Historical treatments for scrotal edema have lacked efficacy. If treated
before fibrosis occurs, surgery can be avoided. A method for conservative
management is outlined.
PMID- 25112024
TI - Female stress urinary incontinence: an evidence-based, case study approach.
AB - Over half of all women are affected by urinary incontinence at some point during
their lives. Due to patients' embarrassment and health care providers' reluctance
to discuss this sensitive subject, many women may go untreated, and in turn,
suffer with disruptive symptoms and co-morbid complications associated with
urinary incontinence. This article highlights a literature review of the
evaluation and management of female stress urinary incontinence using a
corresponding case study example. Increasing awareness and implementing evidence
based, nonsurgical treatment options are essential components of high-quality
care for women with stress urinary incontinence. Urologic nurses and other health
care professionals are in an ideal position to evaluate and identify strategies
for the treatment of female stress urinary incontinence.
PMID- 25112025
TI - Electrocoagulation treatment of metal finishing wastewater.
AB - Electrocoagulation has been found to be a consistent and reliable industrial
wastewater treatment process capable of removing heavy metals to levels well
below pretreatment discharge standards. Results from the testing of a 113 L/min
pilot scale electrocoagulation unit indicated that electrocoagulation was capable
of decreasing the cadmium, chromium, and nickel concentrations from 0.14, 18.1,
and 0.06 parts per million (ppm) to 0.029, 0.039, and 0.020 ppm respectively, at
a 1-min hydraulic retention time. In the presence of a strong chelating
substance, electrocoagulation performance was found to be effective in reducing
both chromium and nickel concentrations to levels well below discharge limits. At
a pH of 8.0, chromium and nickel influent concentrations of 0.328 and 0.062 ppm,
respectively, were reduced to 0.005 and 0.04 ppm. The electrocoagulation removal
efficiency for chromium remained high at over 98% and appeared to be unaffected
by the presence of chelating substances. Utilizing aluminum as the sacrificial
anode improved the removal efficiency of targeted heavy metals when the
industrial wastewater was treated under acidic conditions. At a pH of 5.6, the
influent concentrations of the regulated heavy metals cadmium, chromium, and
nickel were reduced from 0.55, 49.7, and 13.7 ppm, respectively, to 0.013, 2.7,
and 0.8 ppm at a 1-min hydraulic retention time. The results of these tests
suggest that the formation of ferric hydroxide and aluminum hydroxide through the
electrocoagulation process may be an effective approach for treating metal
finishing wastewaters.
PMID- 25112026
TI - Monitoring and remediation of organochlorine residues in water.
AB - This study monitored the presence of organochlorines in drinking water in Kafr-El
Sheikh, Ebshan, Elhamoul, Mehalt Aboali, Fowa, Balteem, and Metobess in the Kafr
El-Sheikh Governorate, Egypt, to evaluate the efficiencies of different
remediation techniques (advanced oxidation processes [AOPs] and bioremediation)
for removing the most frequently detected compound (i.e., lindane) in drinking
water. The results showed the presence of several organochlorine residues at all
water sampling sites. Lindane was detected with high frequency relative to other
detected organochlorines in water. Nano photo-Fenton-like reagent was the most
effective treatment for lindane removal in drinking water. Bioremediation of
lindane by effective microorganisms removed 100% of the initial concentration of
lindane after 23 days of treatment. The study found that there is no remaining
toxicity of lindane-contaminated water after remediation on treated rats relative
to the control with respect to histopathological changes in the liver and
kidneys. Therefore, AOPs, particularly those with nanomaterials and
bioremediation, can be regarded as safe and effective remediation technologies
for lindane in water.
PMID- 25112027
TI - Efficient control of odors and VOC emissions via activated carbon technology.
AB - This research study was undertaken to enhance the efficiency and economy of
carbon scrubbers in controlling odors and volatile organic compounds (VOCs) at
the wastewater collection and treatment facilities of the Bureau of Sanitation,
City of Los Angeles. The butane activity and hydrogen sulfide breakthrough
capacity of activated carbon were assessed. Air streams were measured for odorous
gases and VOCs and removal efficiency (RE) determined. Carbon towers showed
average to excellent removal of odorous compounds, VOCs, and siloxanes; whereas,
wet scrubbers demonstrated good removal of odorous compounds but low to negative
removal of VOCs. It was observed that the relative humidity and empty bed contact
time are one of the most important operating parameters of carbon towers
impacting the pollutant RE. Regular monitoring of activated carbon and VOCs has
resulted in useful information on carbon change-out frequency, packing
recommendations, and means to improve performance of carbon towers.
PMID- 25112028
TI - Partial nitrification in sequencing batch reactors treating low ammonia strength
synthetic wastewater.
AB - Sequencing batch reactors fed with low ammonium strength synthetic wastewater
under C/N ratios of 0.5, 1.5, and 3.0 were used to investigate the transition
from full to partial nitrification. Two strategies for establishing partial
nitrification, aeration duration control and process parameter control, were
compared. The effect of C/N ratio on nitrite accumulation was also evaluated.
Results showed that partial nitrification established by controlling aeration
duration presented better performance with higher nitrite accumulation. An
increase of C/N ratio helped nitrite accumulation; however, non-filamentous
bulking of sludge happened at high C/N ratio. Based on mass balances for
nitrogen, results for nitrogen during full and partial nitrification were
distinct from one another. For low C/N ratio, during full nitrification, almost
100% of NH(4+)-N was oxidized to NO(3-)-N without nitrogen loss; however,
nitrogen loss increased obviously during partial nitrification, which indicated
that dissolved oxygen concentration and C/N ratio influenced nitrogen loss
significantly during nitrification.
PMID- 25112029
TI - Performance evaluation of a dual-flow recharge filter for improving groundwater
quality.
AB - A dual-flow multimedia stormwater filter integrated with a groundwater recharge
system was developed and tested for hydraulic efficiency and pollutant removal
efficiency. The influent stormwater first flows horizontally through the circular
layers of planted grass and biofibers. Subsequently, the flow direction changes
to a vertical direction so that water moves through layers of pebbles and sand
and finally gets recharged to the deep aquifers. The media in the sequence of
vegetative medium:biofiber to pebble:sand were filled in nine proportions and
tested for the best performing combination. Three grass species, viz., Typha
(Typha angustifolia), Vetiver (Chrysopogon zizanioides), and St. Augustine grass
(Stenotaphrum secundatum), were tested as the best performing vegetative medium.
The adsorption behavior of Coconut (Cocos nucifera) fiber, which was filled in
the middle layer, was determined by a series of column and batch studies.The dual
flow filter showed an increasing trend in hydraulic efficiency with an increase
in flowrate. The chemical removal efficiency of the recharge dual-flow filter was
found to be very high in case of K+ (81.6%) and Na+ (77.55%). The pH normalizing
efficiency and electrical conductivity reduction efficiency were also recorded as
high. The average removal percentage of Ca2+ was moderate, while that of Mg2+ was
very low. The filter proportions of 1:1 to 1:2 (plant:fiber to pebble:sand)
showed a superior performance compared to all other proportions. Based on the
estimated annual costs and returns, all the financial viability criteria
(internal rate of return, net present value, and benefit-cost ratio) were found
to be favorable and affordable to farmers in terms of investing in the developed
filtration system.
PMID- 25112030
TI - Methylmercury accumulation and toxicity to cyanobacteria: implications of
extracellural polymeric substances and growth properties.
AB - This investigation examines how extracellular polymeric substances (EPSs) and
environmental factors influence the bioaccumulation of monomethylmercury (MMeHg)
using a culture of Microcystis aeruginosa, which dominates eutrophic reservoir
populations. The identified EPSs were classified as carbohydrates and proteins.
Evaluation of the bioaccumulation of MMeHg in cells by multiple regression
analysis reveals that the concentration of EPSs in filtrate, the initial
concentration of MMeHg in media, and the age of the culture significantly
affected the amount of accumulation of MMeHg. Based on the composition profiles,
the concentrations of soluble carbohydrates were significantly higher in the
cells with bioaccumulated MMeHg than in the control ones. Preliminary results
based on SEM-map investigations suggest that most of the MMeHg accumulated in the
cytoplasm (intracellular). Additionally, the effective concentrations (EC50) of
MMeHg that inhibit the growth of M. aeruginosa were 5.1 to 7.8 microg/L in the
logarithmic phase and 2.5 to 4.6 microg/L in the stationary phase.
PMID- 25112032
TI - Hydrogen production and wastewater treatment in a microbial electrolysis cell
with a biocathode.
AB - The broad application of microbial electrolysis cells (MECs) requires a system
characterized by low cost and high operational sustainability. Biocathode MECs,
which only require bacteria as the cathode catalysts, can satisfy these demands
and have attracted considerable attention in recent years. In this study, we have
examined biocathode alternatives to the typical platinum cathode in a single
chamber, membrane-free MEC. This biocathode MEC has been used for simultaneous
hydrogen production and wastewater treatment. The results showed that hydrogen
production rates increased in response to an increase in voltage. At an applied
voltage of 0.9 V, the biocathode MEC achieved a hydrogen production rate of 0.39
m3 m(-3) d(-1), with a current density of 134 Am(-3), chemical oxygen demand
(COD) removal of 90%, a coulombic efficiency of 63%, a cathodic hydrogen recovery
of 37%, and an energy efficiency based on an electricity input of 67%. The
biocathode demonstrated sufficient electrocatalytic activity and achieved a
performance level comparable to that of the platinum cathode. Moreover, the
substrate that was used to simulate wastewater in this study was efficiently
treated by the MEC.
PMID- 25112031
TI - Hydraulic and hydrogeochemical characteristics of a riverbank filtration site in
rural India.
AB - A riverbank filtration (RBF) system was tested along the Kali River in rural part
of the state of Karnataka in India. The polluted river and water from open wells
served the local population as their principal irrigation water resource and some
used it for drinking. Four RBF wells (up to 25 m deep) were installed. The mean
hydraulic conductivity of the well field is 6.3 x 10(-3) cm/s and, based on
Darcy's law, the water travel time from the river to the principal RBF well (MW3)
is 45.2 days. A mixing model based on dissolved silica concentrations indicated
that, depending on the distance from the river and closeness to irrigated rice
fields, approximately 27 to 73% of the well water originated from groundwater.
Stable isotopic data indicates that a fraction of the water was drawn in from the
nearby rice fields that were irrigated with river water. Relative to preexisting
drinking water sources (Kali River and an open well), RBF well water showed lower
concentration of dissolved metals (60.1% zinc, 27.8% cadmium, 83.9% lead, 75.5%
copper, 100% chromium). This study demonstrates that RBF technology can produce
high-quality water from low-quality surface water sources in a rural, tropical
setting typical for many emerging economies. Further, in parts of the world where
flood irrigation is common, RBF well water may draw in infiltrated irrigation
water, which possibly alters its geochemical composition. A combination of more
than one mixing model, silica together with stable isotopes, was shown to be
useful explaining the origin of the RBF water at this study site.
PMID- 25112033
TI - Formation kinetics of gemfibrozil chlorination reaction products: analysis and
application.
AB - Aqueous chlorination kinetics of the lipid regulator gemfibrozil and the
formation of reaction products were investigated in deionized water over the pH
range 3 to 9, and in two wastewater matrices. Chlorine oxidation of gemfibrozil
was found to be highly dependent on pH. No statistically significant degradation
of gemfibrozil was observed at pH values greater than 7. Gemfibrozil oxidation
between pH 4 and 7 was best represented by first order kinetics. At pH 3,
formation of three reaction products was observed. 4'-C1Gem was the only reaction
product formed from pH 4-7 and was modeled with zero order kinetics. Chlorine
oxidation of gemfibrozil in two wastewater matrices followed second order
kinetics. 4'-C1Gem was only formed in wastewater with pH below 7. Deionized water
rate kinetic models were applied to two wastewater effluents with gemfibrozil
concentrations reported in literature in order to calculate potential mass
loading rates of 4'C1Gem to the receiving water.
PMID- 25112034
TI - Polyphosphate- and glycogen-accumulating organisms in one EBPR system for liquid
dairy manure.
AB - Two enhanced biological phosphorus removal (EBPR) sequencing batch reactors
(SBR1, SBR2) treating liquid dairy manure were operated with the same hydraulic
retention time (HRT) and solids retention time (SRT), but with different aeration
cycles. During eight months of operation, both SBRs achieved good removal of
total phosphorus (P) (TP; 56.8 and 73.5% for SBR1 and SBR2 respectively) and of
orthophosphate (OP; 76.2 vs. 82.7%, P < 0.05). Growth dynamics of presumptive
phosphate-accumulating organisms (PAOs) and glycogen-accumulating organisms
(GAOs) were examined by quantitative polymerase chain reaction (qPCR). SBR1 was
enriched with a greater abundance of PAOs while SBR2 was characterized by a
greater abundance of GAOs. These results demonstrate the capability of EBPR of
dairy manure and challenge conventional wisdom, since greater abundance of PAOs
in EBPR system was not associated with improved OP removal and greater abundance
of GAOs did not indicate deterioration of the EBPR system.
PMID- 25112035
TI - Expert recognition.
PMID- 25112036
TI - QNI celebrates outstanding service.
PMID- 25112038
TI - State nurseries bridge the disadvantaged gap.
PMID- 25112039
TI - Infant mortality rates 'lagging behind' European counterparts, new report
reveals.
PMID- 25112037
TI - Call for HPV vaccine reduction.
PMID- 25112040
TI - New guidelines advocate better birth choice.
PMID- 25112041
TI - Increase in allergy-caused hospital admissions.
PMID- 25112042
TI - Almost half of asthma deaths are avoidable.
PMID- 25112043
TI - Children need health education, says TV doc.
PMID- 25112044
TI - Making progress on children and young people's health.
PMID- 25112045
TI - Not to be sneezed at.
PMID- 25112046
TI - Childhood infestations: prevention and eradication.
PMID- 25112047
TI - 'Is Healthy Start working? Not by a long means'.
PMID- 25112048
TI - Vitamin D--raising awareness of low intakes.
PMID- 25112049
TI - All you need to know about omega-3s.
PMID- 25112050
TI - Factors that influence changes in wheelchair cushion performance over time.
AB - Wheelchair cushions can be used for many hours every day. Like all devices,
cushions degrade over time, losing the ability to provide adequate support.
Little is known about the changes that cushions undergo after typical everyday
use. This project was designed to monitor cushion performance over time with the
objective to identify the most important factors that predict cushion
degradation. Wheelchair users and their cushions were evaluated multiple times.
Information was collected about participants' posture and activities, their
cushions, and use of their cushions. Cushion performance was determined by
measuring interface pressure using a buttock model. Data analysis proceeded in
two steps. First, principal component analysis was run to reduce the number of
variables. Second, multiple regression determined which variables influenced the
interface pressure performance variables. Results indicated that user
characteristics and the manner in which the cushion is used have a greater
influence on cushion performance than the chronological age of the cushion. This
result can be useful to clinicians who should query users about cushion use when
investigating the need to replace a cushion. Finally, this information is
applicable to policies that govern cushion replacement and indicted that wear on
a cushion is not equivocal across users.
PMID- 25112052
TI - Assistive technology as a predictor of general or alternate assessment among
elementary-aged students with autism spectrum disorders.
AB - The No Child Left Behind Act of 2001 specifically mandates that all students
participate in the general assessment process or some form of alternate
assessment as a measure of school accountability for student academic progress.
Although levels of communication difficulties, intellectual impairment, and
specific diagnoses such as autism spectrum disorders (ASDs) are correlated with
increased probability of participating in alternate assessment methods, very
little empirical research has focused on identifying predictors for students'
assessment modality. Archival data from the Special Education Elementary
Longitudinal Study (SEELS; 2005) were used to examine variables that predict
whether elementary school students with ASD participated in the general or
alternate assessment. Results indicated that receptive and expressive
communication abilities appear to influence participation in the general vs.
alternate assessment in tandem with access to assistive technology. Students with
ASDs were approximately 2.71 times more likely to participate in the general
assessment when they had access to assistive technology. Next, we performed a
second, follow-up analysis for only ASD students with communication problems. The
odds ratio value increased to 14.9 indicating that ASD students with
communication problems that had access to assistive technology were almost 15
times more likely to participate in the general assessment than students with
communication problems without access to assistive technology.
PMID- 25112051
TI - Analysis of electrode shift effects on wavelet features embedded in a myoelectric
pattern recognition system.
AB - Myoelectric pattern recognition systems can translate muscle contractions into
prosthesis commands; however, the lack of long-term robustness of such systems
has resulted in low acceptability. Specifically, socket misalignment may cause
disturbances related to electrodes shifting from their original recording
location, which affects the myoelectric signals (MES) and produce degradation of
the classification performance. In this work, the impact of such disturbances on
wavelet features extracted from MES was evaluated in terms of classification
accuracy. Additionally, two principal component analysis frameworks were studied
to reduce the wavelet feature set. MES from seven able-body subjects and one
subject with congenital transradial limb loss were studied. The electrode shifts
were artificially introduced by recording signals during six sessions for each
subject. A small drop in classification accuracy from 93.8% (no disturbances) to
88.3% (with disturbances) indicated that wavelet features were able to adapt to
the variability introduced by electrode shift disturbances. The classification
performance of the reduced feature set was significantly lower than the
performance of the full wavelet feature set. The results observed in this study
suggest that the effect of electrode shift disturbances on the MES can
potentially be mitigated by using wavelet features embedded in a pattern
recognition system.
PMID- 25112053
TI - A paired outcomes study comparing two pediatric wheelchairs for low-resource
settings: the regency pediatric wheelchair and a similarly sized wheelchair made
in Kenya.
AB - This comparative study of two similar wheelchairs designed for less-resourced
settings provides feedback to manufacturers, informing ongoing improvement in
wheelchair design. It also provides practical familiarity to clinicians in
countries where these chairs are available, in their selection of prescribed
wheelchairs. In Kenya, 24 subjects completed 3 timed skills and assessments of
energy cost on 2 surfaces in each of 2 wheelchairs: the Regency pediatric chair
and a pediatric wheelchair manufactured by the Association of the Physically
Disabled of Kenya (APDK). Both wheelchairs are designed for and distributed in
less-resourced settings. The Regency chair significantly outperformed the APDK
chair in one of the energy cost assessments on both surfaces and in one of three
timed skills tests.
PMID- 25112054
TI - Improving mouse controlling and movement for people with Parkinson's disease and
involuntary tremor using adaptive path smoothing technique via B-spline.
AB - Many input devices are available for interacting with computers, but the computer
mouse is still the most popular device for interaction. People who suffer from
involuntary tremor have difficulty using the mouse in the normal way. The target
participants of this research were individuals who suffer from Parkinson's
disease. Tremor in limbs makes accurate mouse movements impossible or difficult
without any assistive technologies to help. This study explores a new assistive
technique-adaptive path smoothing via B-spline (APSS)-to enhance mouse
controlling based on user's tremor level and type. APSS uses Mean filtering and B
spline to provide a smoothed mouse trajectory. Seven participants who have
unwanted tremor evaluated APSS. Results show that APSS is very promising and
greatly increases their control of the computer mouse. Result of user acceptance
test also shows that user perceived APSS as easy to use. They also believe it to
be a useful tool and intend to use it once it is available. Future studies could
explore the possibility of integrating APSS with one assistive pointing
technique, such as the Bubble cursor or the Sticky target technique, to provide
an all in one solution for motor disabled users.
PMID- 25112055
TI - Use of assistive technologies in academic libraries: a survey.
AB - The present article attempts to highlight the use of assistive technologies in
academic libraries in India, the United Kingdom, the United States, and Canada.
It dwells upon the use and importance of assistive technologies in general and
their use for visually challenged learners in particular. Further, it gives
suggestions for implementing assistive technologies in academic libraries for
making visually challenged students self-reliant learners in accomplishing their
academic and research pursuits. The present study adopted convenience sampling
for collecting the data, which was collected between December 15, 2012 and
January 18, 2013.
PMID- 25112056
TI - Homebirth and the microbiome.
PMID- 25112057
TI - Tricks of the trade.
PMID- 25112058
TI - Marion's message: birth and the human future.
PMID- 25112059
TI - Coming to twins.
PMID- 25112060
TI - Why all the fuss about twins?
PMID- 25112061
TI - The wonderful world of twin birth.
PMID- 25112062
TI - The voice of reason.
PMID- 25112063
TI - Twin birth in rural Nevada.
PMID- 25112065
TI - Maternal placentophagy as an alternative medicinal practice in the postpartum
period.
PMID- 25112064
TI - Helping a mother with twins: choose your words wisely.
PMID- 25112066
TI - In memory of Marsden Wagner. A friend to midwives, 1930-2014.
PMID- 25112067
TI - Zachary and Jack.
PMID- 25112068
TI - Jade and Cole.
PMID- 25112069
TI - Rose and Philippa.
PMID- 25112070
TI - Temperance and Genevieve.
PMID- 25112072
TI - GBS updates from a homebirth perspective.
PMID- 25112071
TI - Catharina Schrader: a midwife of 18th-century Friesland.
PMID- 25112073
TI - Easing afterpains: wisdom from the Midwives College of Utah.
PMID- 25112074
TI - Utilizing chiropractic for optimal pregnancy and birth outcomes.
PMID- 25112075
TI - Moving from independent midwifery to a consultation service.
PMID- 25112076
TI - Belly buddies.
PMID- 25112077
TI - From Robin Lim in the Philippines.
PMID- 25112078
TI - Is there a time or circumstance in the 3rd stage of labor when it is appropriate
to massage the fundus?
PMID- 25112079
TI - What are your comfort tips for 1st or 2nd stage labor?
PMID- 25112080
TI - [Comparison of efficacy on functional constipation treated with
electroacupuncture of different acupoint prescriptions: a randomized controlled
pilot trial].
AB - OBJECTIVE: To evaluate preliminarily the efficacy on functional constipation
treated with electroacupuncture of different acupoint prescriptions. METHODS: One
hundred and four patients were randomized into a front-mu and back-shu points
group (19 cases), a he-sea points group (34 cases), a he-sea, front-mu and back
shu points group (26 cases) and a western medication control group (25 cases). In
the front-mu and back-shu points group, electroacupuncture was applied at
bilateral Tianshu (ST 25) and Dachangshu (BL 25). In the he-sea points group,
electroacupuncture was applied at bilateral Quchi (LI 11) and Shangjuxu (ST 37).
In the he-sea, front-mu and back-shu points group, electroacupuncture was applied
at unilateral Tianshu (ST 25), Dachangshu (BL 25), Quchi (LI 11) and Shangjuxu
(ST 37). In the three groups above, the treatment was given 5 times a week in the
first two weeks and 3 times a week in the next two weeks. In the western
medication control group, mosapride citrate tablets were prescribed for oral
administration, 1 table (5 mg) each time, 3 times a day, continuously for 4
weeks. The period of research was 9 weeks, including 1 week for baseline
evaluation, 4 weeks for treatment and 4 weeks for follow-up. The weekly
defecation frequency was taken as primary index, while the defecation difficulty
and life quality score were taken as the secondary indices for the efficacy
evaluation after treatment and in follow-up. RESULTS: According to the intention
to-treat (ITT) analytic principle, 104 cases were all enrolled in the final
analysis. (1) After treatment, the weekly frequency of defecation was all
increased significantly in the four groups (P < 0.05, P < 0.01). The efficacy of
the three electroacupuncture groups was similar to that of western medication
control group (P > 0.05). In follow-up, the increasing effect on the weekly
frequency of defecation was maintained in the he-sea points group (P < 0.01),
superior to the front-mu and back-shu points group and the western medication
control group (P < 0.05, P < 0.01); the weekly frequency of defecation was not
improved in the rest three groups (P > 0.05). (2) After treatment, defecation
difficulty was relieved in the he-sea points group, the he-sea, front-mu and back
shu points group and the western medication control group (P < 0.05, P < 0.01).
In follow-up, the improvements were still significant in the he-sea points group
and the he-sea, front-mu and back-shu points group (both P < 0.01). (3) After
treatment, the life quality score was significantly improved in the patients of
the he-sea points group (P < 0.05). The difference was not significant in the
rest three groups as compared with that before treatment (all P > 0.05).
CONCLUSION: The weekly frequency of defecation is increased effectively after
treatment in the three electroacupuncture groups and the efficacy is similar to
mosapride citrate tablets. The bilateral Quchi (LI 11) and Shangjuxu (ST 37) in
he-sea acupoints increase significantly the weekly frequency of defecation,
relieve defecation difficulty and improve life quality. Acupuncture efficacy is
sustained for 4 weeks. This acupoints prescription is the best in the treatment
of functional constipation.
PMID- 25112081
TI - [Clinical efficacy observation of acupuncture at suliao (GV 25) on improving
regain of consciousness from coma in severe craniocerebral injury].
AB - OBJECTIVE: To compare the clinical therapeutic effects differences between
acupuncture at Suliao (GV 25) and Shuigou (GV 26) on promoting regain of
consciousness from coma in severe craniocerebral injury. METHODS: Based on
regular emergency treatments of neurosurgery, eighty-two cases of craniocerebral
injury who were under stable condition were randomly divided into an observation
group (42 cases) and a control group (40 cases). Suliao (GV 25) was selected as
main aupoint, while Laogong (PC 8) and Yongquan (KI 1), etc. were selected as
adjuvant acupoints and Neiguan (PC 6), Sanyinjiao (SP 6), Yifeng (TE 17) and
Wangu (GB 12), etc. were selected as matching acupoints in the observation group
where a strong needle manipulation was applied to improve the regain of
consciousness. The main acupoint of Shuigou (GV 26) along with identical adjuvant
acupoints and matching acupoints in the observation group were selected in the
control group with identical strong needle manipulation. The treatment was given
once a day in both groups, five times per week and ten times were considered as
one session. The immediate clinical symptoms after acupuncture at Suliao (GV 25)
and Shuigou (GV 26) were observed as well as Glasgow coma scale (GCS) before the
treatment, after 45 days and 90 days of treatment to assess the resuscitation
time and rate. Also the clinical efficacy was compared between both groups.
RESULTS: The occurrence rate of sneezing reflex was 85.7% (36/42) in the
observation group, which was higher than 25.0% (10/40) in the control group (P <
0.01). The average resuscitation time was (64.6 +/- 19.4) days in the observation
group, which was obviously shorter than (73.8 +/- 14. 6) days in the control
group (P < 0.05). The resuscitation rate was 88.1% (37/42) in the observation
group, which was similar to 75.0% (30/40) in the control group (P > 0.05).
Compared before the treatment, GCS were both improved after the treatment in two
groups (both P < 0.01). The 90-day GCS was 9.52 +/- 2.32 in the observation
group, which was superior to 8.47 +/-2.14 in the control group (P < 0.05). The
curative and markedly effective rate was 45.2% (19/42) in the observation group,
which was superior to 22.5% (9/40) in the control group (P < 0.05). CONCLUSION:
The effect of acupuncture at Suliao (GV 25) on improving regain of consciousness
from coma in severe craniocerebral injury is positive. It could specifically
improve sneezing reflex and stimulate respiratory center, which has more obvious
effect than acupuncture at Shuigou (GV 26).
PMID- 25112082
TI - [Stroke-induced acroparalysis treated with xunjingcuiqi needling technique: a
randomized controlled trial].
AB - OBJECTIVE: To observe the impacts on the muscle strength in the patients of
stroke-induced acroparalysis treated with Xunjingcuiqi needling technique.
METHODS: One hundred patients were randomized into a Xunjingcuiqi group and a
routine acupuncture group, 50 cases in each group. In the routine acupuncture
group, the routine acupuncture technique was adopted at the main acupoints, such
as Shangxing (GV 23), Baihui (GV 20), Dicang (ST 4), Quchi (LI 11), Huantiao (GB
30) and Zusanli (ST 36), etc. In Xunjingcuiqi group, on the basis of the routine
acupuncture technique, Xunjingcuiqi needling technique (pricking technique was
quickly applied with the filiform needle along the running course of meridian to
promote the conduction of meridian qi) was added. For the patients being hard to
feel the needling sensation and with the muscle strength of 0 to 1 degree,
Dongzhencuiqi technique was supplemented at shu-stream points of yang meridians
(after qi arrival, the needling manipulation with limb movement was given to
promote the conduction of meridian qi). The treatment was given once every day in
the two groups. Ten treatments made one session. Three sessions of treatment were
required. At the end of each session treatment, the muscle strength and clinical
efficacy were assessed. RESULTS: In the 1st, 2nd and 3rd sessions of treatment,
20, 24 and 36 cases achieved the 3 to 5 degrees muscle strength in Xunjingcuiqi
group, respectively; and 6, 10 and 15 cases achieved the 3 to 5 degrees muscle
strength in the routine acupuncture group. The differences were significant
statistically in comparison of the two groups (P < 0.01, P < 0.05). The markably
effective rates were 60.0% (30/50), 64.0% (32/50) and 70.0% (35/50) after the
1st, 2nd and 3rd sessions of treatment in Xunjingcuiqi group, respectively; and
those were 38.0% (19/50), 44.0% (22/50) and 46.0% (23/50) in the routine
acupuncture group, respectively. The differences were significant in the 1st and
3rd sessions of treatment between the two groups (both P < 0.05). CONCLUSION:
Xunjingcuiqi needling technique combined with routine acupuncture achieves the
apparent superior efficacy on acroparalysis induced by ischemic stroke as
compared with the simple routine acupuncture. Xunjingcuiqi needling technique
obviously improves muscle strength and shortens the duration of sickness.
PMID- 25112083
TI - [Clinical observation on medulla oblongata palsy after brainstem infarction
treated with electroacupuncture at eight-neck-occiput points].
AB - OBJECTIVE: To compare the differences in the efficacy on speech and swallowing
dysfunction of medulla oblongata palsy (MOP) after brainstem infarction between
electroacupuncture at eight-neck-occiput points and routine acupoints. METHODS:
Seventy-two patients were randomized into a neck-occiput points group and a
meridian points group, 36 cases in each one. In the neck-occiput points group,
the eight-neck-occiput points (Neck 1-4 points, Occiput 1-4 points) were
selected. In the meridian points group, Lianquan (CV 23), Futu (LI 18), Tongli
(HT 5), Hegu (LI 4) and the others were selected. Electroacupuncture was used in
the two groups, dense-dispersion wave, retaining for 30 min. The treatment was
given once a day, 5 treatments a week. Totally, 4 weeks were required. The
symptom scores of speech and swallowing dysfunction were observed before and
after treatment in the two groups. The efficacy was compared between the two
groups. RESULTS: The scores of speech and swallowing dysfunction were improved
significantly after treatment in the two groups (P < 0.05, P < 0.01). The results
in the neck-occiput points group were better than those in the meridian points
group (both P < 0.01). The curative rate of speech dysfunction was 30.6% (11/36)
and that of swallowing dysfunction was 22.2% (8/ 36) in the neck-occiput points
group, which were better than 11.1% (4/36) and 5.6% (2/36) in the meridian points
group, respectively. The differences were significant in comparison of the two
groups (P < 0.01, P < 0.05). CONCLUSION: Electroacupuncture at eight-neck-occiput
points achieves a better efficacy on speech and swallowing dysfunction of MOP
after brainstem infarction as compared with the routine acupoints. This therapy
is characterized as more accurate point localization and safer operation.
PMID- 25112084
TI - [Controlled observation of the efficacy on motion sickness in the prevention and
treatment with jianpixingnao needling therapy].
AB - OBJECTIVE: To verify the efficacy of Jianpi-xingniao needling therapy on
prevention and treatment of motion sickness. METHODS: Sixty volunteers of motion
sickness were randomized into an acupuncture group and a delayed acupuncture
group, 30 cases in each one. In the acupuncture group, acupuncture was given at
Baihui (GV 20), Sishencong (EX-HN 1), Neiguan (PC 6), Zusanli (ST 36) and Hegu
(LI 4). The needles were retained for 20 min. The treatment was given twice a
week and 10 treatments were required. In the delayed acupuncture group,
acupuncture was postponed, meaning no acupuncture during observation stage.
Graybel scale was adopted to observe the score of symptoms and physical signs of
the subjects of motion sickness before and after intervention. The efficacy was
compared between the two groups. RESULTS: Twenty-five cases in the acupuncture
group and 22 cases in the delayed acupuncture group were included in the
statistical analysis. The score of symptoms and physical signs of motion sickness
was reduced significantly after treatment in the acupuncture group as compared
with that before treatment (10.12 +/- 3.37 vs 0.92 +/- 0.40, P < 0.05). The score
in the acupuncture group was lower apparently than that in the delayed
acupuncture group (0.92 +/- 0.40 vs 9.86 +/- 2.53, P < 0.05). The difference was
not significant before and after treatment in the self-comparison of the delayed
acupuncture group (P > 0.05). The total effective rate was 96.0% (24/25) in the
acupuncture group, which was significantly better than 0.0% (0/22) in the delayed
acupuncture group (P < 0.01). CONCLUSION: Jianpixingniao needling therapy
relieves the symptoms of motion sickness in the patients and achieves a better
clinical efficacy.
PMID- 25112085
TI - [Efficacy observation on acupuncture for essential hypertension of yin deficiency
due to yang hyperactivity pattern].
AB - OBJECTIVE: To observe the clinical effects of essential hypertension treated with
acupuncture at Siguan [Hegu (LI 4) and Taichong (LR 3)], Quchi (LI 11) and
Xingjian (LR 2). METHODS: Sixty cases of essential hypertension were randomly
divided into an acupuncture group and a medication group, 30 cases in each group.
Two groups of acupoint, which were (1) Siguan [Hegu (LI 4) and Taichong (LR 3)]
and (2) Quchi (LI 11), Xingjian (LR 2), were selected alternatively in the
acupuncture group, once everyday. In the medication group, captopril was
prescribed for oral administration 25 mg per time, three times per day. Seven
days made one session in both groups and totally three sessions were required.
RESULTS: (1) After treatment, the blood pressure were decreased significantly in
the two groups (all P < 0.01). Compared with the medication group, the diastolic
pressure after 14 days, 21 days of treatment in the acupuncture group was
decreased significantly (both P < 0.01). (2) In the terms of TCM syndrome score,
the improvement of dizziness, soreness and weakness of waist and knees,
palpitations was significant in the acupuncture group compared with that in the
medication group(all P < 0.05). (3) The acupuncture group had less adverse
reactions compared with the control group (P < 0.05). CONCLUSION: Acupuncture at
Hegu (LI4) and Taichong (LR 3), Quchi (LI 11) and Xingjian (LR 2) can effectively
decrease blood pressure; the effect of controlling diastolic pressure is better
than captopril. It can also improve the symptoms of dizziness, soreness and
weakness of waist and knees, and palpitations.
PMID- 25112086
TI - [Efficacy observation on chrondromalacia patellae treated with fire needling
technique at high stress points].
AB - OBJECTIVE: To compare the clinical efficacy differences between fire needling
technique of filiform needle at high stress points and regular acupuncture on
chrondromalacia patellae so as to provide the better therapy for the treatment of
this disease. METHODS: Sixty cases of chrondromalacia patellae were randomized
into a fire needling group (28 cases) and a routine acupuncture group (32 cases).
In the fire needling group, 5 to 6 high stress points were localized according to
the symptoms, palpation and imaging condition and were stimulated with fire
needling technique of filiform needle. The treatment was given once every two
days, 5 treatments made one session. In the routine acupuncture group, the
regular acupuncture was applied at Dubi (ST 35), Xiguan (LR 7), Yanglingquan (GB
34), Yinlingquan (SP 9), Zusanli (ST 36), etc. The treatment was given once every
day, 5 treatments made one session. Lysholm score, VSA score, patella title angle
(PTA) and lateral patella angle (LPA) of the affected knees before and after
treatment, as well as the clinical efficacy after treatment were observed in the
two groups. RESULTS: After treatment, Lysholm score, VSA score, PTA and LPA were
all improved apparently in the two groups (all P < 0.01). After the treatments,
the improvements in Lysholm score, VSA score, PTA and LPA in the fire needling
group were more obvious than those in the routine acupuncture group (all P <
0.05). The effective rate was 92.9% (26/28) in the fire needling group, better
than 87.5% (28/32) in the routine acupuncture group (P < 0.01). CONCLUSION: The
fire needling technique of filiform needle at the high stress points relieves the
clinical symptoms of chrondromalacia patellae and recovers the biodynamical
structure of patellae.
PMID- 25112087
TI - [Clinical study on primary osteoporosis treated with spreading moxibustion for
warming yang and activating blood circulation].
AB - OBJECTIVE: To observe the efficacy on primary osteoporosis treated with spreading
moxibustion for warming yang and activating blood circulation so as to provide
the effective clinical therapeutic methods for osteoporosis. METHODS: Sixty cases
of primary osteoporosis were randomized into a spreading moxibustion group (30
cases) and a calcium tablet group (30 cases). In the calcium tablet group,
caltrate was prescribed for oral administration, 600 mg per day. In the spreading
moxibustion group, on the basis of the treatment as the calcium tablet group, the
spreading moxibustion was applied at Dazhui (GV 14) to Yaoshu (GV 2) for warming
yang and activating blood circulation. The duration of treatment was 12 weeks.
Visual analogue scale (VAS) score, TCM clinical symptom score and bone mineral
density (BMD) were observed and compared before and after treatment in the
patients between the two groups. RESULTS: VAS scores were reduced apparently
after treatment in the two groups (both P < 0.01) and the results in the
spreading moxibustion group were obviously superior to that in the calcium tablet
group (2.36 +/- 0.43 vs 4.52 +/- 0.35, P < 0.01). BMD were all increased in the
two groups (P < 0.05, P < 0.01) and the results in the spreading moxibustion
group were superior to those in the calcium tablet group (both P < 0.05). The
total clinical effective rate was 86.67% (26/30) in the spreading moxibustion
group, apparently better than 63.33% (19/30) in the calcium tablet group (P <
0.05). TCM clinical symptom scores after treatment were all reduced apparently in
the two groups (both P < 0.01), and the result in the spreading moxibustion group
was obviously superior to that in the calcium tablet group (4.72 +/- 1.90 vs 6.82
+/- 2.30, P < 0.01). The total effective rate of TCM symptoms was 93.33% (28/30)
in the spreading moxibustion group, apparently better than 70.00% (21/30) in the
calcium tablet group (P < 0.05). CONCLUSION: The combined therapy of spreading
moxibustion for warming yang and activating blood circulation and the oral
administration of caltrate apparently relieves pain and TCM clinical symptoms,
improves BMD in the patients of osteoporosis and achieves definite clinical
efficacy in the patients of osteoporosis.
PMID- 25112088
TI - [Dragon moxibustion for 32 cases of low back muscle fasciitis].
PMID- 25112089
TI - [Discussion on disease spectrum treated with acupuncture at shenmen (HT 7) and
its compatibility based on bibliometrics].
AB - The modern literatures on the diseases treated with acupuncture at Shenmen (HT 7)
were collected. Using literature statistical analysis in bibliometrics, the
common compatibility of Shenmen (HT 7) and the disease spectrum were analyzed so
as to provide the references of the diseases that can be treated with acupuncture
at Shenmen (HT 7). It was found that 39 kinds of diseases and symptoms, mainly
nerve system disedses, could be treated with acupuncture at Shenmen (HT 7),
including insomnia, depression, anxiety and dementia. Shenmen (HT 7) was seldom
used alone. Instead, it was commonly used along with Baihui (GV 20), Sanyinjiao
(SP 6), Neiguan (PC 6), Sishencong (EX-HN 1) and Taicong (LR 3).
PMID- 25112090
TI - [Analysis on clinical palpation laws of muscle meridian focus in scapulohumeral
periarthritis].
AB - OBJECTIVE: To explore the distribution rules of proximal and distal focus of
muscle meridian region in scapulohumeral periarthritis. METHODS: Three hundred
and six shoulder joints of affected side were selected in 216 patients of
scapulohumeral periarthritis. Under the guidance of muscle meridian theory, with
the anatomical characteristics of muscle meridian focuses, the frequency and
location where proximal and distal focus appeared were calculated by palpation.
RESULTS: The percentages of the frequency that the focus of muscle meridian of
Hand-Yangming, Hand-Shaoyang, Hand-Taiyang, and three yin meridians of hand
appeared at proximal points of shoulder joint were 25.6% (1 146/5 657), 30.9% (1
749/5 657), 19.0% (1 075/5 657), and 24.5% (1 387/5 657), respectively, the
focuses of muscle meridian region were Jianyuci, Juguci, Xiaoshuoci, Naohuici,
etc. The percentages of the frequency that the focus of muscle meridian region
appeared at distal points of shoulder joint were 31.77% (287/905), 23.2%
(210/905), 10.9% (99/905), and 34.1% (304/905), the focuses of muscle meridian
were Yangxici, Shousanlici, Yangchici, etc. CONCLUSION: The location and
frequency of proximal and distal focus of muscle meridian in scapulohumeral
periarthritis are closely related with the anatomical structure and biomechanical
characteristics of the shoulder joints, thus new therapy for scapulohumeral
periarthritis is implied.
PMID- 25112091
TI - [A secondary discussion on acupoint characteristic].
AB - With references of historical materials and modern literature regarding acupoint
characteristic, a secondary analysis on the concept, origin, related factors and
research methods in present research of acupoint characteristic is performed. The
acupoint characteristic should be considered as an acupoint inherent attribute
that could explain physiological and pathological manifestations at the same
time, including location attribute and function attribute, which is related with
time and treatment method. Some re-thinking on acupoint characteristic is
proposed as well as advice on further research method and direction, hoping to
promote the research development of acupoint characteristic.
PMID- 25112092
TI - [Fire needle combined with small needle-knife for 58 cases of chronic lumbar
muscle strain].
PMID- 25112093
TI - [Effects of controllable dynamic inhaled exposure of moxa smoke on LDL-r, ICAM-1
and morphology of heart tissue in rats].
AB - OBJECTIVE: To observe the change of lipid metabolism and vascular endothelium as
well as morphology of heart tissue in rats who were long-time exposed to moxa
smoke with different concentrations in order to provide reference for safety
assessment of moxa smoke on cardiovascular system. METHODS: One hundred and sixty
eighty Wistar rats were randomly divided into a control group, a low
concentration group, a median-concentration group and a high-concentration group,
42 rats in each one. The rats were exposed to moxa smoke with concentration of
0%, 10%, 40% and 70%, respectively, for 20 min per day. After continuous
intervention for six months, enzyme-linked immunosorbent assay (ELISA) was
applied to measure the level of low density lipoprotein-receptor (LDL-r) and
intercellular adhesion molecule-1 (ICAM-1) in blood serum in each group; the
slices of heart tissue were stained with hematoxylin-eosin staining method to
observe morphology change of heart tissue. RESULTS: (1) After the intervention of
moxa smoke, the levels of LDL-r and ICAM-1 in the low-concentration group were
not statistically different from those in the control group (both P > 0.05); the
level of LDL-r in the median-concentration group was significantly increased,
which was statistically different from that in the control group [(3.87 +/- 0.27)
mg/mL vs (2.12 +/- 0.13) mg/mL, P < 0.01], however, the content of ICAM-1 was not
obviously changed; although the level of LDL-r in the high-concentration group
was presented with an escalating trend, it was not statistically different from
that in the control group (P > 0.05) while the level of ICAM-1 was obviously
increased (P < 0.01). (2) Under the light microscope, the abnormalities of
cardiac muscle fibers and myocardial cell in each group were not been observed.
CONCLUSION: The long-time intervention of low-concentration moxa smoke has no
significant effects on lipid metabolism and vascular endothelium of rats,
indicating that clinical application of low-concentration moxa smoke is
relatively safe. The long-time intervention of moderate-concentration moxa smoke
could significantly increase the clearance rate of cholesterol, implying the
beneficial regulation of moxa smoke on lipid metabolism. The high-concentration
moxa smoke could induce certain damage to vascular endothelium but its mechanism
is in need of further research. The pathologic change of heart tissue could not
be induced by moxa smoke with any concentration.
PMID- 25112094
TI - [Effects of electroacupuncture with manifestation-root acupoint combination on
ultrastructure and biosynthesis in mitochondrial of quadriceps femoris in rats
with insulin resistance].
AB - OBJECTIVE: To explore the mechanism of electroacupuncture on improving insulin
resistance of rat from aspects of morphology and function of mitochondrial in
quadriceps femoris. METHODS: Forty-eight 8-week Wistar rats (female and male in
half) were randomly divided into a normal group (16 rats, group A), a model
control group (16 rats, group B), a model plus electroacupuncture (EA) group (8
rats, group C) and a model plus sham acupoint EA group (8 rats, group D). Group A
was given with basic diet while high-fat diet was applied in the group B, group C
and group D for 8 weeks to establish model of insulin resistance. After the model
establishment, "Guanyuan" (CV 4), "Zhongwan" (CV 12), "Zusanli" (ST 36) and
"Fenglong" (ST 30) were selected according to acupoint combination of
manifestation-root in the group C, while four points in non-meridian area where 1
to 2 mm next to the acupoints used in group C were selected in the group D. The
treatment was given 15 min per time with 1 mA of intensity and 2 Hz in frequency,
5 times per week for totally 8 weeks. The transmission electron microscope was
adopted to observe mitochondria structure, and chemical colorimetry was used to
test the activity of adenosine triphosphate (ATP) synthase and phosphomolybdic
acid colorimetry was applied to measure the content of ATP. RESULTS: After the
treatment, the body mass was (401.63 +/- 109.81) g in the group B, which was
significantly higher than (305.88 +/- 62.72) g in the group A (P < 0.05);
morphological structure of mitochondrion was damaged, showing swelling and
deformation; the activity of ATP synthase was decreased (P < 0.05) and the
content of ATP in tissue of quadriceps femoris was also obviously lowered (P <
0.05). The body mass was (294.13 +/- 53.78) g in the group C, which was
significantly lower than that in the group B (P < 0.05); the damaged
mitochondrion was restored and merged among each other; the activity of ATP
synthase was increased (P < 0.05); the content of ATP in tissue of quadriceps
femoris was obviously lifted (P < 0.05). The results in group D were not
different from those in group B. CONCLUSION: The electroacupuncture with
manifestation-root acupoint combination could improve the recovery of damaged
structure of mitochondrion and promote the merge among each other, which could
enhance oxidizing capacity, lower body mass and improve synthetic rate of ATP.
PMID- 25112095
TI - [Ninety-one cases of intractable hiccups treated by acupuncture of relaxing the
bowels and keeping the adverse stomach-qi downswards].
PMID- 25112096
TI - [Low back pain of cold-damp pattern treated with electric-thermal Bian-stone
therapy and traditional moxibustion: a randomized controlled trial].
AB - OBJECTIVE: To compare the difference in the efficacy on low back pain of cold
damp pattern between electric-thermal Bian-stone therapy and moxibustion box
therapy. METHODS: Forty-one cases of low back pain of cold-damp pattern were
randomized into an electric-thermal Bian-stone therapy group (group A, 26 cases)
and a box moxibustion therapy group (group B, 15 cases). In the group A, the
electric-thermal Bian-stone was placed over Shenshu (BL 23) and Weizhong (BL 40).
The temperature of stone was adjusted in accordance with patient's comfort. In
the group B, moxibustion box was used over Shenshu (BL 23) and Weizhong (BL 40).
The treatment was given once every day or every two days. Ten treatments made one
session. The symptom and physical signs score of low back pain and the score of
cold-damp syndrome were observed before and after treatment in the patients.
RESULTS: The symptom and physical signs score of low back pain and the score of
cold-damp syndrome were all improved in the two groups (all P < 0.01). The
changing rate of symptom and physical signs and syndrome were (37.04 +/- 32.68)%
and (22.85 +/- 29.95)% in the group A, and were (47.29 +/- 22.08)% and (23.89 +/-
22.53)% in the group B, respectively, without significant difference in
comparison between the two groups (all P > 0.05). CONCLUSION: The efficacy on low
back pain of cold-damp pattern treated with the electric-thermal Bian-stone
therapy is similar to that of moxibustion box therapy. This therapy is
characterized as more convenient, safer operation and less pollution.
PMID- 25112098
TI - [Fire-needle with sulfur for 40 cases of epidemic parotitis].
PMID- 25112097
TI - [Acupuncture combined with moxibustion for 32 cases of anal pain after anus
operation].
PMID- 25112099
TI - [The enlightenment of Fu's subcutaneous needling on pain medicine].
AB - Fu's subcutaneous needling (FSN) is a modern approach developed from traditional
Chinese acupuncture. It could give some stimulation in the subcutaneous region
that has a quick and long-lasting effect on soft tissue injuries and some of the
internal medicine diseases. It is a safe approach without adverse reaction.
Through analysis of the features and possible mechanism of FSN, it is believed
that research on mechanism of FSN is beneficial to the development of modern
medicine, especially to pain management.
PMID- 25112100
TI - [Acupuncture combined with Tuina for 10 cases of sacroiliac joint sclerosing
osteitis].
PMID- 25112101
TI - [Present situation and development of acupuncture and moxibustion in Turkey].
AB - The development and status of acupuncture-moxibustion in Turkey in the fields of
education, legal establishment, treatment, etc. are introduced. There are four
distinguished features of acupuncture-moxibustion development in Turkey: (1) The
geographical position of the country as the link of Europe and Asia, has resulted
in the special feature of acupuncture-moxibustion transmission and development.
It combines both the traditional theories from the East and the modified and
modern techniques from the West. (2) The combination of theories and clinical
practice started when acupuncture-moxibustion was first introduced. (3) The
application of acupuncture-moxibustion has gone through a process from
spontaneous transmission among the people to legalization by the government, from
disorderly to orderly, and from market behavior to government-lead regulation,
which has powerfully promoted healthy development of the medicine. (4)
Acupuncture-moxibustion education provided by registered universities has
guaranteed the quality of the education itself and the competency of the
professionals. It has raised the scientific and normative character of
application and increased the credibility of the people, and also has ensured the
sustainability of acupuncture-moxibustion development by providing qualified
professionals.
PMID- 25112102
TI - [Case of Raynaud disease].
PMID- 25112103
TI - [Quality assessment on guidelines of clinical practice in acupuncture and
moxibustion: a study based on AGREE].
AB - The quality of guidelines of clinical practice in acupuncture and moxibustion was
evaluated with AGREE II tool. After retrieval of officially-issued guidelines of
clinical practice in acupuncture and moxibustion from 2004 to 2013, totally 5
types of evidence-based guidelines of clinical practice in acupuncture and
moxibustion were acquired, including depression, herpes zoster, pseudobulbar
palsy after stroke, migraine and Bell's palsy. With AGREE II tool, independent
score in six areas, including guideline's scope and purpose, participants and
personnel, preciseness, clarity and readability, applicability and editorial
independence were analyzed to perform a comprehensive evaluation in the end. The
assessment results indicated that the score of editorial independence in evidence
based guidelines of clinical practice in acupuncture and moxibustion was the
highest, averagely 97.9%, which was followed by clarity and readability (83.3%),
participants and personnel (78.1%), preciseness (75.6%), the scope and purpose
(68.1%) and the applicability (62.5%). The total evaluation score was all 6
points in the five guidelines with recommended as comprehensive evaluation
advice. This study results indicate that although the guideline of clinical
practice in acupuncture and moxibustion is low in number, the total quality is
considerable.
PMID- 25112104
TI - [A further discussion on acupuncture treatment plan of facial neuritis in
Evidence-based Guidelines of Clinical Practice in Acupuncture and Moxibustion].
AB - The treatment plan of facial neuritis in Evidence-based Guidelines of Clinical
Practice in Acupuncture and Moxibustion (2011 edition) is discussed, and case
information of facial neuritis during the recent five years in department of
acupuncture and moxibustion, PLA General Hospital, is retrospectively analyzed.
In accordance with anatomy of the facial nerve to form the acupuncture
prescription, the detailed diagnosis and treatment method for facial neuritis are
introduced. The advantages of the diagnosis and treatment method for facial
neuritis are summarized, hoping to establish a more comprehensive, standardized
and unified treatment plan.
PMID- 25112105
TI - [Long snake moxibustion for 38 cases of gout].
PMID- 25112106
TI - [Origin and development of umbilical therapy in traditional Chinese medicine].
AB - The origin and development of umbilical therapy in traditional Chinese medicine
is explored from related literature in the history. As a result, the Shang period
is regarded as initial period of umbilical therapy, while periods from Han
Dynasty, Jin Dynasty and Southern-Northern Dynasties to Sui Dynasty and Tang
Dynasty could be taken as stage of primary development. Time from Song Dynasty,
Jin Dynasty and Yuan Dynasty to Ming and Qing Dynasties is believed as mature
stage. Also the manipulation, application principle, indications and
contraindications of umbilical therapy are explained. A brief overview of modern
development of umbilical therapy is also described.
PMID- 25112107
TI - [Acupuncturists and their academic contributions in Lingnan area: a review].
AB - The academic thoughts of Lingnan acupuncture and moxibustion have been an
essential part of Lingnan medicine. By exploration and arrangement of Lingnan
medicine and books, journals and literatures regarding acupuncture and
moxibustion, the ancient and modern acupuncturists and their academic
contributions in Lingnan area were reviewed. As a result, the number of Lingnan
acupuncturists and their works was low before Qing Dynasty, while from the
Republic of China era to People's Republic of China, a considerable amount of
acupuncturists emerged with quite a lot of works. By exploration and arrangement
of Lingnan acupuncturists and their works and academic opinion, the acupuncture
moxibustion school characterized by Lingnan could be formed and developed.
PMID- 25112108
TI - [Discussion on professor SHAO Jing-Ming's academic opinion of focusing spirit].
AB - During professor SHAO Jing-ming's academic research and medical practice, his
academic opinion of focusing spirit is gradually developed. In terms of nurturing
the spirit, attention should be paid on persistence as well as everyday health
maintenance and exercise to nurture the spirit of physician. In terms of clinical
diagnosis and treatment, patients' psychology, employment and life status should
be observed and experienced, which could bring more methods to take essential
care of patients' spirit. The treatment should work with psychological
counseling, advocating that based on patients' qi and spirit, various forms of
treatment methods should be properly used, such as acupuncture or moxibustion or
combination of acupuncture and medicine, along with simple acupoint selection and
harmony medication. Before clinical treatment of acupuncture, calming the mind is
critically emphasized to make a clear diagnosis. During the acupuncture, calming
and focusing the mind is necessary as well as emphasizing the details, so
acupuncture could be integrated with Chi Gong to create a new warming-sensation
technique. In a word, the academic opinion of focusing spirit is shedding an
inspiring light upon further study.
PMID- 25112109
TI - [Case of lacrimal duct obstruction].
PMID- 25112110
TI - [Twenty cases of spinocerebellar atrophy treated by multi-needling in rows at
occiput].
PMID- 25112111
TI - [Clinical randomized controlled trials of acupoint catgut-embedding for simple
obesity: a meta-analysis].
AB - The clinical therapeutic effect of acupoint catgut-embedding for simple obesity
was systemically analyzed to provide reference and assistance for its clinical
treatment and research. By searching in the CBM, CNKI, VIP, Wanfang, Pubmed,
Springer and Medline databases, clinical randomized controlled trials (RCT) of
acupoint catgut-embedding for simple obesity published from Jan, 2009 to July,
2013 were collected while Revman 5. 2 software was applied to perform the Meta
analysis. Totally 19 articles were acquired with 1 658 cases involved. The
effective rate was selected as primary outcome measure in 19 articles. The Meta
analysis was performed among homogeneous researches. The results indicated that
compared with other therapies, pooled OR of acupoint catgut-embedding was 2.45
with 95% CI [1.81, 3.32]; in the test for overall effect, Z = 5.81, implying the
efficacy difference of two therapies was significant in the treatment of simple
obesity (P < 0.01). In subgroups analysis, in the event of treatment session with
more than 3 months, compared with other therapies, pooled OR of acupoint catgut
embedding was 2.61 with 95% CI [1.53, 4.46]; in test for overall effect, Z =
3.51, implying the efficacy difference of two therapies was significant in the
treatment of simple obesity (P < 0.01); in the event of treatment session with
less than 3 months, compared with other therapies, pooled OR of acupoint catgut
embedding was 2.38 with 95% CI [1.65, 3.44]; in test for overall effect, Z =
4.46, implying in the treatment of simple obesity the efficacy difference of two
therapies was significant (P < 0.01). Compared with electroacupuncture, OR of
acupoint catgut-embedding was 1.79, 95% CI [1.08, 2.95] (P = 0.02). Compared with
acupuncture, OR of acupoint catgut-embedding was 1.89, 95% CI [1.16, 3.09] (P =
0.01), which explained that compared with electroacupuncture and acupuncture, the
efficacy of acupoint catgut-embedding was significantly different. In a word, the
clinical efficacy of acupoint catgut-embedding is superior to other therapies in
the treatment of simple obesity.
PMID- 25112112
TI - [Clinical utility of reflectance confocal microscopy for the non-invasive
diagnosis of lentigo maligna melanoma].
AB - BACKGROUND: Lentigo maligna melanoma (LMM), a melanoma subtype that arises on sun
damaged facial skin, is difficult to diagnose clinically. Patients and physicians
are reluctant to perform unnecessary facial biopsies. Reflectance confocal
microscopy (RCM) is a novel technique for non-invasive skin imaging at cellular
level resolution. RCM increases the accuracy of melanoma diagnosis. AIMS: To
describe the diagnostic utility of RCM in cases of clinically and
dermatoscopically equivocal pigmented skin lesions suspicious for LMM. METHODS:
This is a retrospective case series derived from the population of patients
undergoing periodic skin cancer screening at a tertiary hospital clinic that
specializes in skin cancer diagnosis. All patients consented to RCM imaging as an
ancillary test prior to the decision on performing a biopsy in the facial lesion.
RESULTS: We report on four patients who presented clinically and
dermatoscopically equivocal pigmented skin lesions in the head and neck region,
with differential diagnosis of LMM. Furthermore, in two patients, a prior
incisional biopsy indicated a benign diagnosis upon histopathological analysis.
In all cases, RCM examination showed specific criteria for LMM. The RCM diagnosis
of LMM allowed direct referral for excisional surgery in three patients. In
another patient, RCM findings guided incisional biopsy-site selection to a focus
that revealed histopathology clear-cut criteria for LMM. CONCLUSIONS: RCM is a
very useful adjunct to the non-invasive diagnosis of LMM.
PMID- 25112113
TI - [Cutis verticis gyrata as an early rare presenting sign of acromegaly].
AB - Cutis verticis gyrata (CVG) is a descriptive term for a dermal sign in which deep
furrows and convoluted ridges are seen upon the scalp. They are formed due to
thickening of the skin folds of the scalp and produce an appearance that
resembles the gyri of the brain. The condition is classified primary when the
etiology is unknown or neurologically based. CVG will be considered secondary
when a definite cause, systemic or localized, is responsible for the sign. We
describe a 34 year-old male who was presented with a one-month history of
arthralgia in his interphalangeal joints. His physical examination revealed scalp
changes compatible with CVG, which appeared 3 years earlier. Following a thorough
investigation of the patient, acromegaly was diagnosed. Although CVG is a rare
condition, it has been described in patients with acromegaly. The appearance of
SVG as an early sign of acromegaly makes this case unique and important. In a
patient developing CVG, acromegaly and other treatable disorders should always be
excluded.
PMID- 25112114
TI - [Peripheral arthritis in polymyalgia rheumatica].
AB - Polymyalgia rheumatica is characterized by aching and stiffness of the shoulder,
the pelvic girdles and the neck. Peripheral joint involvement is less recognized
by the medical community as a sign of the disease. In this article we present two
patients whose disease was manifested by peripheral symptoms. The frequency,
manifestations and the pathogenesis of the disorder are discussed and the
importance of recognition of these symptoms and signs of the disease is stressed.
PMID- 25112115
TI - [Unique mechanism in heart-shaped balloon burst resulting in blunt ocular
injury].
AB - We have previously shown that heart-shaped balloons have a different explosion
mechanism than spherical balloons in which the former splits into two rubber
parts still attached to the balloon base with a backward whiplash motion. This
backward whiplash motion may cause significant blunt ocular trauma if the balloon
is inflated by mouth. In this article, the energy of the blunt ocular trauma is
estimated by the high speed camera photos analysis of the balloon burst.
Furthermore, we describe the followup of eight patients with ocular trauma
following inflation of heart-shaped balloons.
PMID- 25112116
TI - [Lentigo maligna: a diagnostic and therapeutic challenge].
AB - Lentigo maligna is an early type of melanoma which appears in sun damaged skin.
The clinical diagnosis as well as the pathological diagnosis are a challenge to
the clinician and the pathologist since atypical proliferation of melanocytes is
a common finding in chronically sun exposed skin. The use of a dermatoscope and
in vivo reflectance confocal microscopy as diagnostics aids can make the clinical
diagnosis more accurate. Mohs micrographic surgery has become the standard of
care, if available, for lentigo maligna.
PMID- 25112117
TI - [Posterolateral rotatory instability of the elbow].
AB - The term posterolateral rotatory instability (PLRI) was coined in 1991 by
O'Driscoll to describe the instability of the elbow caused by injury to the
lateral ulnar collateral ligament (LUCL). This condition, which is usually
preceded by a traumatic dislocation of the elbow, is the most common type of
chronic instability of the elbow. In this type of instability, the radius and
ulna rotate externally in relation to the distal humerus, leading to posterior
displacement of the radial head relative to the capitellum. lateral elbow pain,
clicking, popping and snapping are possible symptoms. The diagnosis of PLRI
relies on a high index of suspicion and on a detailed physical examination.
Several tests have been described including apprehension tests and examination
under anesthesia. Surgical treatment with reconstruction of the lateral
collateral ligament complex yields successful results. In this review we
summarize the current knowledge of the pathoanatomy, presentation, physical
examination, diagnostic tests and management of chronic posterolateral rotatory
instability of the elbow.
PMID- 25112118
TI - [Physical exercise for people with cerebral palsy: effects, recommendations and
barriers].
AB - The management goal of cerebral palsy (CP) is improving functionality, locomotion
and independence. Treatment programs commonly encompass adapted physical activity
(APA). This review summarizes the knowledge regarding the effects and
recommendations for APA in persons with CP. In addition, barriers to APA in this
population are reviewed. The available literature on benefits of APA to persons
with CP has focused mainly on youth. The components of the APA programs generally
consist of strength, aerobic and flexibility training. There is no empirical
evidence that strength-training increases spasticity in people with CP.
Furthermore, strength-training may increase strength and the ability to perform
daily activities. Aerobic-training is especially important as persons with CP
typically have low cardiorespiratory fitness and high prevalence of cardiac
disease. However, limited published evidence exists on aerobic-training effects
in this population. Nonetheless, the evidence suggests that aerobic-training in
persons with CP can improve physiological outcomes, yet the influence of these
changes on participation has not been investigated sufficiently. Stretching
exercise is a common treatment for spasticity. Surprisingly, there is
inconclusive evidence for the effectiveness of stretching exercise for persons
with CP. Despite the importance attributed to APA for people with CP, low levels
of physical activity have been reported in this population. However, when
caregivers perceive greater benefits of exercise, individuals with CP are more
likely to be active. In contrast, barriers to APA include costs of APA programs,
limited means of transportation to APA facilities, lack of information regarding
APA facilities and limited appropriate exercising equipment in the APA
facilities.
PMID- 25112119
TI - [Breastfeeding and childhood leukemia and lymphoma].
AB - In the last 30 years there has been an increase in the incidence rate of
childhood cancer in the western world. Although the 5-year survival rate from
childhood cancer has increased significantly over the years due to advances in
treatment technologies, cancer is still one of the leading causes of death among
children in westernized countries. Leukemia and lymphoma are two of the most
common cancer types in children and together account for about 45% of all
childhood cancers. Nevertheless, very little is known of the etiology of
childhood leukemia and lymphoma. Several studies had looked into the question of
a relationship between infant nutrition--breastfeeding or lack thereof--and the
risk of childhood leukemia and lymphoma as part of the "infective agent theory".
This review aims to describe the current scientific evidence regarding the
possible connection between breastfeeding and childhood malignancies, with an
emphasis on childhood and adolescent leukemia and lymphoma. To that end, a
systematic review of past studies has been conducted using Pubmed. Furthermore,
the bibliographies of the relevant studies found on Pubmed were consulted.
Studies were divided into two groups: original studies, and systematic reviews
and meta analyses. Based on the Literature review, it is evident that the results
are still inconclusive--some studies found a connection between breastfeeding and
a lower risk of childhood leukemia and lymphoma, while others found no
connection. The variability in breastfeeding and childhood cancer rates among the
different populations where studies were conducted is large. In view of that
variability and the differing results of former studies, there is a need to
continue research. Israel, with characteristics of both a westernized country and
a more traditional society with respect to parity and breastfeeding, is a good
place to conduct such a study, with possible important implications for public
health.
PMID- 25112120
TI - [Consensus conferences as a tool for implementing national policy--a review and
international comparison].
AB - The consensus conference (CC) is a professional methodology for comprehensive
decision-making on controversial healthcare issues. The CC is based on health
technology assessment, combining an in-depth review of the literature,
consultation with experts and discussion within the framework of a broad panel of
public and medical representatives. The process has many advantages but was also
faces criticism; it reflects democratic deliberation, and reveals an opportunity
to bridge the conceptual gap between policymakers and the public. The process
enables citizens to be involved in decisions regarding unsolved medical dilemmas,
as well as the means for resolving these questions, in an open transparent way.
Those who criticize this mechanism refer to the restricted understanding of
medical topics by lay-men, leading to only a negligible influence by nonmedical
participants. However, the range of successful recommendations varies between
countries. Many constraints raise the need for bending and matching the original
model to different scenarios around the world; in the USA, an effort was made to
preserve professional and academic principles, while in European countries
flexibility led to evolving methodologies, and other frameworks developed.
Currently, the most common methodology is the "citizen jury", empowering the
participation of representatives of the public, as a mirror to preferences of the
individual and society. Despite resistance, consensus conferences remain a
successful model for policy-making in healthcare for over 30 years. During 2009
the method was even expended for global discussion involving representatives from
38 nations.
PMID- 25112121
TI - [Spiritual care in hospitals and other healthcare settings in Israel--a
profession in the making].
AB - Faced with a serious, incurable illness, disability, and other symptoms, both
physical and mental, some patients find themselves wondering about the meaning of
their Lives. They need the help of a professional who can perceive their mental
turmoil and identify their spiritual needs, and who knows how to help them find
meaning in their uncertain state. Spiritual care providers are professionals
whose role it is to provide patients with support in their hour of need, to help
them preserve their identity in life-threatening situations, and to help them re
endow their world with meaning, employing a special language and set of tools
that enable patients to get in touch with their spiritual resources and internal
powers of healing. Spiritual care providers serve on the medical staff in Western
countries. In the United States, some 2,600 are employed in general hospitals,
psychiatric hospitals, long-term care facilities, and palliative care units.
Approximately ten years ago, the profession began developing in Israel. Today,
dozens of spiritual care providers are now working in the healthcare system.
There is a spiritual care network with 21 member organizations. Although the
profession is laying down roots in the healthcare system in this country, it is
still in its infancy and has to contend with substantial barriers and challenges,
including professional recognition, creating positions, and identifying sources
of funding for positions. The profession still has much room to grow as it is
further incorporated into the healthcare system and continues undergoing
adaptation to the Israeli cultural setting.
PMID- 25112122
TI - [Confidence interval calculation for small numbers of observations or no
observations at all].
AB - Confidence interval calculation is a common statistics measure, which is
frequently used in the statistical analysis of studies in medicine and life
sciences. A confidence interval specifies a range of values within which the
unknown population parameter may lie. In most situations, especially those
involving normally-distributed data or large samples of data from other
distributions, the normal approximation may be used to calculate the confidence
interval. But, if the number of observed cases is small or zero, we recommend
that the confidence interval be calculated in more appropriate ways. In such
cases, for example, in clinical trials where the number of observed adverse
events is small, the criterion for approximate normality is calculated.
Confidence intervals are calculated with the use of the approximated normal
distribution if this criterion is met, and with the use of the exact binomial
distribution if not. This article, accompanied by examples, describes the
criteria in which the common and known method cannot be used as well as the
stages and methods required to calculate confidence intervals in studies with a
small number of observations.
PMID- 25112123
TI - [Tocophobia--its origin, prevalence and implications].
AB - Tocophobia is defined as fear from pregnancy in general and fear of vaginal
delivery in particular. This is a relatively prevalent phenomenon, which
originates due to traumatic events in the past: whether as a result of previous
bad obstetric experience or from other non-obstetric related events. Unstable
mental disorder may also be expressed as tocophobia. As there is no common
agreement regarding the definition of tocophobia, conservative methods of
treatment have not proven effective. Male tocophobia is also recognized and can
be negatively influential on female males and spouses. The ultimate solution to
tocophobia is an elective cesarean section following maternal request, with no
obvious medical indication. This creates ethical problems to the attending
physicians.
PMID- 25112124
TI - [Clinical pathological conference: abdominal masses and purulent ascites].
AB - A 91 year old patient presented with constipation, abdominal distension, weakness
and anorexia lasting for two days. Computed tomography revealed multiple
peritoneal masses with significant growth within days and local invasiveness
without regard to anatomical boundaries. No lymphadenopathy or hepatosplenomegaly
were found. Abdominal paracentesis showed 60,000 cells/mm3 presumed to be
neutrophils. During follow-up, there were no clinical or radiographic signs of
peritonitis. Trans-abdominal true-cut biopsy from the peritoneal masses was
consistent with diffuse large B cell lymphoma germinal center B cell type,
clinically presenting as peritoneal lymphomatosis. FISH cytogenetic study
identified single BLC-6 gene in the tumor infiltrating lymphocytes. We speculated
that this aberration in the patient's immune system cells contributed to this
rare, unusual and aggressive lymphoma presentation in an otherwise non-immune
compromised patient.
PMID- 25112125
TI - [Sick child, sick parents].
PMID- 25112126
TI - Has Jackson talken over our MSMA?
PMID- 25112127
TI - Change of heart: transplantation in Mississippi.
PMID- 25112128
TI - Axillary lymph node treatment in breast cancer: an update.
AB - Sentinel lymph node biopsy (SLNbx) is the standard of care for staging of breast
cancer. Patients with a negative sentinel lymph node biopsy (SLNbx) do not
undergo axillary lymph node dissection (ALND) or regional nodal irradiation
(RNI). However, if a patient has a positive sentinel lymph node biopsy (SLNbx),
then axillary lymph nodal dissection (ALND) is the standard treatment. Recent
studies, notably the Z-0011 and MA-20 trials, have demonstrated that omission of
axillary lymph nodal dissection (ALND) did not decrease overall survival. MA-20
demonstrated that inclusion of regional nodal irradiation (RNI) in addition to
axillary lymph nodal dissection (ALND) did increase survival when compared to
axillary lymph nodal dissection (ALND) without regional nodal irradiation (RNI).
Ongoing studies are randomizing patients to axillary lymph nodal dissection
(ALND) or regional nodal irradiation (RNI) after a positive sentinel lymph node
biopsy (SLNbx).
PMID- 25112129
TI - Mississippi provisional reportable disease statistics. March 2014.
PMID- 25112130
TI - Dr. W H. H. Lewis of Fayette (1866-1936).
PMID- 25112131
TI - President's page. Thoughts on Medicaid expansion.
PMID- 25112132
TI - A return to the Asclepeia: a physician's enduring obligation to his or her
patients.
PMID- 25112133
TI - Rationing vs. reengineering: the 21st century challenge for American health care.
PMID- 25112134
TI - Sustainable access to data for postmarketing medical product safety surveillance
under the amended HIPAA Privacy Rule.
PMID- 25112135
TI - Privacy vs. progress: research exceptionalism is bad medicine.
AB - Attitudes about privacy are changing in non-research settings, but these
attitudinal shifts do not seem to be affecting the way regulators and ethicists
think about the need to protect people from the risks of harm resulting from use
of personal information in research studies (so-called "informational risks").
Increasingly, people routinely share personal information (including health
information) online. And yet, a proposal has been made to restrict further the
use of existing data, such as electronic medical records, for purposes of
scientific research, even when personal identifiers have been removed. The
disproportionate focus on "informational" risks in research is a form of research
exceptionalism. This practice of treating research risks with greater caution
than we treat other risks encountered in daily life is a legacy of past research
abuses. Although understandable in historical context, this exceptionalism is
harmful when it unreasonably interferes with scientific advances that could
improve human health and welfare.
PMID- 25112136
TI - Big data proxies and health privacy exceptionalism.
PMID- 25112137
TI - Crossing 138: two approaches to churn under the Affordable Care Act.
AB - A predicted side effect of the Medicaid expansion and state-based Exchanges under
the Affordable Care Act is churn. Churn is the shifting into and out of
eligibility for insurance affordability programs due to income changes. Because
the line between Medicaid and Exchange eligibility is fine -138% of the federal
poverty level -millions of Americans are expected to gain and lose eligibility.
Frequently, this churning undermines continuity of care, raises costs, and
frustrates those affected. This article explores two proposed programs to
mitigate the effects of churn: the Basic Health Program and the Bridge Program.
This article evaluates both programs' ability to mitigate the effects of churn,
the likely side effects to states' implementing them, and legal and practical
obstacles to their implementation. It concludes that the Bridge Program is the
better approach.
PMID- 25112138
TI - Antitrust and the future of nursing: federal competition policy and the scope of
practice.
PMID- 25112139
TI - How Medicare Part D, Medicaid, electronic prescribing, and ICD-10 could improve
public health (but only if CMS lets them).
AB - A simple change to the Medicare and Medicaid outpatient prescription drug billing
systems could improve patient safety and the systems' long-term fiscal stability.
Including diagnosis codes on prescription drug claims (codes already in use for
other billing purposes) would transform the Medicare Part D and Medicaid
prescription drug claims databases into powerful public health research tools-
ones that could provide much-needed (and, to date, elusive) information on how
prescription drugs work in vulnerable patient populations underrepresented in
clinical research. Achieving the full potential of this proposal, though, depends
upon the federal agency responsible for Medicare and Medicaid, the Centers for
Medicare and Medicaid Services (CMS), maintaining its current reimbursement
policy, which is perhaps best characterized as one of benign neglect of the
statutory standard for coverage. If, instead of continuing coverage for the vast
majority of prescription drugs, CMS decided to deny payment for the millions of
prescriptions falling short of the statutory standard (and thus avoid spending
billions of federal health care dollars), prescribers would find themselves in an
ethical dilemma between truth-telling and effectively treating their patients.
Due to the systemic incentives for prescribers and pharmacists to miscode
diagnoses in order to get CMS to pay for the prescription drugs needed by
patients, the decision to treat patients effectively in the short-term under a
strict coverage enforcement policy would undermine the potential to more
effectively treat vulnerable patients, reduce prescription errors, and properly
allocate federal health care dollars in the future. Even in the midst of a
financial crisis, or perhaps especially because of our current financial crisis,
we cannot afford to sacrifice improved patient safety and better informed long
term management of federal health care dollars for a short-term reduction in
federal spending on prescription drugs.
PMID- 25112141
TI - Mandatory school-based mental health services and the prevention of school
violence.
PMID- 25112140
TI - Repairing the therapist? Banning reparative therapy for LGB minors.
PMID- 25112142
TI - "Death is different": limiting health care for death row inmates.
PMID- 25112143
TI - Unwrapped: how the Los Angeles County safer sex in the Adult Film Industry Act's
condom mandate hurts performers & violates the First Amendment.
PMID- 25112144
TI - Sealing the record: an analysis of jurisdictional variations of juvenile sex
offender record sealing laws.
PMID- 25112145
TI - Sexual and reproductive health and HIV in border districts affected by migration
and poverty in Tanzania.
AB - OBJECTIVES: To assess HIV knowledge, attitudes, sexual practices and sexual and
reproductive health (SRH) service delivery in border areas of Tanzania, with a
view to support the prioritisation of SRH interventions in border areas. METHODS:
The target sample comprised randomly selected people living near the border, aged
15 to 49 years. To gather information, we utilised: (i) a standardised
questionnaire (n = 86; 42 men and 44 women) previously used in national household
surveys conducted by the Tanzanian government; (ii) focus group discussions (ten
male groups, n = 47; ten female groups, n = 51); and (iii) semi-structured
interviews with service providers (n = 37). RESULTS: The mean number of sexual
partners, frequency of multiple concurrent partnerships and engagement in
transactional sex were significantly higher in the border community than in the
national population. Knowledge about HIV was comparable with that in the general
population. Access to SRH services was limited in the border areas. CONCLUSION:
Efforts to reduce HIV transmission and to improve SRH in the border areas should
focus on gaps in service delivery rather than education and information
activities alone. In addition, multi-sectorial efforts spanning the health,
social, legal and private sectors addressing gender imbalances and poverty
alleviation are imperative for reducing poverty-driven unsafe transactional sex.
PMID- 25112146
TI - New approaches in commercial development of artificial oxygen carriers.
PMID- 25112148
TI - Interventions to improve adherence to first-line antibiotics in respiratory tract
infections. The impact depends on the intensity of the intervention.
AB - BACKGROUND: Many interventions aimed at improving the quality of antibiotic
prescribing have been investigated, but more knowledge is needed regarding the
impact of different intensity interventions. OBJECTIVES: To compare the effect of
two interventions, a basic intervention (BI) and intensive intervention (II),
aimed to improve the adherence to recommendations on first-line antibiotics in
patients with respiratory tract infections (RTIs). METHODS: General practitioners
(GPs) from different regions of Spain were offered two different interventions on
antibiotic prescribing. They registered all patients with RTIs during 15 days
before (2008) and after (2009) the intervention. GPs in Catalonia were exposed to
BI including prescriber feedback, clinical guidelines and training sessions
focused on appropriate antibiotic prescribing. The other group of GPs was exposed
to an II, which besides BI, also included training and access to point-of-care
tests in practice. RESULTS: The GPs registered 15 073 RTIs before the
intervention and 12 760 RTIs after. The antibiotic prescribing rate reduced from
27.7% to 19.8%. Prescribing of first-choice antibiotics increased after the
intervention in both groups. In the group of GPs following the BI, first-line
antibiotics accounted for 23.8% of antibiotics before the intervention and 29.4%
after (increase 5.6%, 95% confidence interval (CI): 1.2-10%), while in the group
of GPs following the II these figures were 26.2% and 48.6% (increase 22.4%, 95%
CI: 18.8-26%), respectively. CONCLUSION: Multifaceted interventions targeting GPs
can improve adherence to recommendations for first-line antibiotic prescribing in
patients with RTI, with intensive interventions that include point-of-care
testing being more effective.
PMID- 25112147
TI - Perception of high school students on risk for acquiring HIV and utilization of
voluntary counseling and testing (VCT) service for HIV in Debre-berhan Town,
Ethiopia: a quantitative cross-sectional study.
AB - BACKGROUND: Human immunodeficiency virus (HIV) epidemic among youth is largely
ignored and remains invisible to both young people themselves and to the society
as a whole. Thus, the aim of the study was to assess the extent of perception
risk of HIV and utilization of voluntary counseling and testing (VCT) service
among high school students at Debre-berhan Town, Amhara Regional State, Ethiopia.
METHODS: A cross-sectional study was carried out from November 2010 up to January
2011 among secondary school students at Debre-berhan Town. Perception risk and
VCT use were considered as dependant variables. A stratified random sampling
technique was used to recruit study participants by taking schools as strata.
Semi-structured self-administered questionnaire was used to collect the necessary
data. Data was entered and analyzed using SPSS version 17.0. P-value < 0.05 was
considered as statistically significant. RESULTS: A total of 339 students were
consented to participate in the study and the response rate was 96.3%. The
student ages' were ranged from 15 up to 24 years. Among the study participants,
30 (8.8%) had sexual contact and the mean age of first sexual encounter was 16.4
(SD =2.05) years. Of sexually active students, 12 (40%) had sex with different
persons within the last 6 months, 13 (43.3%) had ever used condom and 15 (50%)
had used VCT service. There was no statistically significant association between
risk perception towards HIV infection and ever use of VCT service (AOR (95% CI) =
1.0(0.30, 4.02). CONCLUSIONS: Some students were engaged in risky sexual behavior
even though they had heard about HIV/AIDS. The perception of risk for acquisition
of HIV infection and utilization of VCT were low. Thus, education on topic of
HIV/AIDS through integrating as part of school curriculum and encouraging the
existing health institutions to provide youth-friendly sexual counseling services
including VCT for HIV are strongly recommended.
PMID- 25112149
TI - Exploring precarious employment and women's health within the context of U.S.
microenterprise using focus groups.
AB - OBJECTIVE: Nursing has been a leader in exploring social determinants of health
within the context of U.S. microenterprise and women's health. The purpose of
this study was to explore precarious employment within the context of
microenterprise and women's health using focus groups with clientele from New
Mexico (NM). The specific aims were to identify (1) the health concerns of low
income women who utilized resources from Women's Economic Self-Sufficiency Team
(WESST), and (2) the meaning of precarious employment in low-income women's
lives. DESIGN AND STRATEGY: Fourteen women, ranging in age from 21-65 years, who
were affiliated with regional WESST sites around NM participated in focus groups
and completed a demographic questionnaire. MEASURES: Focus group data were
analyzed using content analysis. The degree of interrater agreement was
determined by calculating the Cohen's kappa, percentage agreement, and prevalence
adjusted and bias-adjusted kappa (PABAK). RESULTS: Two broad themes emerged from
these data: (1) Working for Yourself and (2) Strategies. Although the women
identified concerns about participation in microenterprise, flexibility, freedom,
and feeling purposeful were motivators to pursue a small business. The kappa
statistics on the five transcripts revealed poor inter-rater agreement, yet
PABAK, which is a more sophisticated inter-rater reliability index, indicated
that inter-rater agreement between the two raters was satisfactory. CONCLUSION:
Despite the challenges associated with microenterprise in the US, women found
value in working for themselves.
PMID- 25112150
TI - Perforated colonic tubulovillous adenoma--a rare presentation.
PMID- 25112151
TI - McKittrick-Wheelock syndrome complicated by Enterococcus faecalis endocarditis: a
unique combination.
PMID- 25112152
TI - Hydrotaea similis Meade (Diptera: Muscidae) newly reported from a human cadaver:
a case report and larval morphology.
AB - A human cadaver is an attractive breeding habitat for necrophagous insects and
for those species that are predators of necrophages. One of the important tasks
of forensic entomologists is to provide a reliable list of species associated
with decomposing bodies both in the adult and larval stages. We present here a
case of a human cadaver discovered in Central Sweden and the insect fauna
associated with it. This is the first report of Hydrotaea similis larvae
developing in a dead human body. The larvae of H. similis have only recently been
studied and, therefore, even if previously they had been collected during
forensic casework or experiments, the larvae could not have been properly
identified, except if reared to the adult stage. To facilitate future studies and
casework, detailed descriptions are provided here of the morphology of third
instar larvae of both H. dentipes and H. similis using combined SEM and light
microscopy techniques. We describe characters that allow for easy species
identification and discrimination of these two forensically important and closely
related species.
PMID- 25112153
TI - Acute intoxication due to tert-amyl alcohol--a case report.
AB - We presented a case of 28 year-old male, who was found in a deep coma complicated
with acute respiratory failure because of recreational intoxication with tert
amyl alcohol (TAA). The TAA blood level at the admission was 83 MUg/mL determined
by gas chromatography-mass spectrometry (GC-MS). In the last few months
popularity of TAA among alcohol and drug addicted people in Europe is still
growing. The main reasons of these are: self-healing of addiction, low price of
this xenobiotic compare to alcohol, and problem to detect this xenobiotic in
generally used screening tests.
PMID- 25112155
TI - Association between transforming growth factor-beta1gene-509C/T polymorphism and
susceptibility of IgA nephropathy: a meta-analysis.
AB - A role for transforming growth factor-beta1gene has been suggested in the
etiology of IgA nephropathy. However, results have been inconsistent. In this
study, a meta-analysis was performed to further clarify the association between
transforming growth factor-beta1-509C/T gene polymorphism and the susceptibility
of IgA nephropathy. PubMed, EMBASE, Web of Science, CNKI, WanFang, and VIP Data
were searched for eligible studies. Pooled odds ratios (ORs) with 95% confidence
intervals were calculated using a fixed-effects model or random-effects model. A
total of eight publications involving 1355 IgA nephropathy patients and 1464
controls met the inclusion and were analyzed. The pooled ORs for the association
between TGF-beta1gene-509C/T polymorphism and IgA nephropathy risk were not
statistically significant under all genetic models (for CT+TT vs. CC: OR = 1.09;
95% CI = 0.92-1.29, p = 0.490; for TT vs. CT+CC: OR = 1.14; 95% CI = 0.94-1.38, p
= 0.081; for CC vs. TT: OR = 0.87; 95% CI = 0.69-1.08, p = 0.195; for C allele
vs. T allele: OR = 0.92; 95% CI = 0.83-1.03, p = 0.149). In the stratified
analysis by ethnicity, results also showed no significant association between TGF
beta1 gene-509C/T polymorphism and IgA nephropathy risk in both European and
Asian populations. This meta-analysis does not support the hypothesis that TGF
beta1 gene-509C/T polymorphism is a risk factor for the development of IgA
nephropathy.
PMID- 25112154
TI - Prolonged ingestion of ovalbumin diet by sensitized mice improves the metabolic
consequences induced by experimental food allergy.
AB - The prevalence of food allergy is rising in the western world. Allergen
restriction is the chosen treatment in this condition, but continuous ingestion
of the antigen has shown positive results in clinical trials. In a previous
study, we have shown several allergic and metabolic alterations after 7 days of
ovalbumin (OVA) ingestion by sensitized mice. The aim of this study was to
investigate whether prolonged ingestion of antigen by sensitized mice would
reverse the metabolic consequences caused by experimental food allergy. For this,
allergic and metabolic parameters were analysed after prolonged ingestion of an
OVA diet by OVA-sensitized mice. As shown previously, after 7 days of OVA
consumption, sensitized mice showed increased serum levels of anti-OVA
immunoglobulin (Ig)E and IgG1, aversion to the antigen ingestion, marked body and
adipose tissue weight loss, followed by adipose tissue inflammation and decreased
serum levels of adipokines, glucose and triglycerides. However, after 14 days of
oral challenge, sensitized mice showed an anti-OVA IgE level similar to the mice
that were only sensitized, but the specific IgG1 did not change. With this
prolonged ingestion of OVA, sensitized mice were protected from OVA-induced
anaphylaxis when the antigen was given systemically at a dose of 2 mg/animal.
Moreover, various parameters analysed were significantly ameliorated, including
adipose tissue inflammation, body and adipose tissue loss, as well as serum
levels of adipokines and triglycerides. Therefore, our data suggest that
prolonged ingestion of OVA by sensitized mice results in an improvement of the
metabolic consequences caused by experimental food allergy.
PMID- 25112156
TI - Hydrogenation of amides catalyzed by a combined catalytic system of a Ru complex
with a zinc salt.
AB - Addition of catalytic amounts of zinc salts facilitated the hydrogenation of
amides catalyzed by a ruthenium complex bearing 2-(diphenylphosphino)ethanamine
(L1). The combined catalytic system of the ruthenium complex [RuCl2(L1)2] with a
zinc salt such as Zn(OCOCF3)2 mediated hydrogenation of various amides under mild
conditions to afford the corresponding primary alcohols.
PMID- 25112157
TI - Affinity purified anti-citrullinated protein/peptide antibodies target antigens
expressed in the rheumatoid joint.
AB - INTRODUCTION: A major subset of patients with rheumatoid arthritis (RA) is
characterized by the presence of circulating autoantibodies directed to
citrullinated proteins/peptides (ACPAs). These autoantibodies, which are commonly
detected by using an enzyme-linked immunosorbent assay (ELISA) based on synthetic
cyclic citrullinated peptides (CCPs), predict clinical onset and a destructive
disease course. In the present study, we have used plasma and synovial fluids
from patients with RA, for the affinity purification and characterization of anti
CCP2 reactive antibodies, with an aim to generate molecular tools that can be
used in vitro and in vivo for future investigations into the pathobiology of the
ACPA response. Specifically, this study aims to demonstrate that the surrogate
marker CCP2 can capture ACPAs that bind to autoantigens expressed in vivo in the
major inflammatory lesions of RA (that is, in the rheumatoid joint). METHODS:
Plasma (n = 16) and synovial fluid (n = 26) samples were collected from RA
patients with anti-CCP2 IgG levels of above 300 AU/mL. Total IgG was isolated on
Protein G columns and subsequently applied to CCP2 affinity columns. Purified
anti-CCP2 IgG was analyzed for reactivity and specificity by using the CCPlus(r)
ELISA, in-house peptide ELISAs, Western blot, and immunohisto
/immunocytochemistry. RESULTS: Approximately 2% of the total IgG pool in both
plasma and synovial fluid was CCP2-reactive. Purified anti-CCP2 reactive
antibodies from different patients showed differences in binding to CCP2 and
differences in binding to citrullinated peptides from alpha-enolase, vimentin,
fibrinogen, and collagen type II, illustrating different ACPA fine-specificity
profiles. Furthermore, the purified ACPA bound not only in vitro citrullinated
proteins but, more importantly, in vivo-generated epitopes on synovial fluid
cells and synovial tissues from patients with RA. CONCLUSIONS: We have isolated
ACPAs from plasma and synovial fluid and demonstrated that the CCP2 peptides,
frequently used in diagnostic ELISAs, de facto act as surrogate antigens for at
least four different, well-characterized, largely non-cross-reactive, ACPA fine
specificities. Moreover, we have determined the concentration and proportion of
CCP2-reactive IgG molecules in rheumatoid plasma and synovial fluid, and we have
shown that the purified ACPAs can be used to detect both in vitro- and in vivo
generated citrullinated epitopes by various techniques. We anticipate that these
antibodies will provide us with new opportunities to investigate the potential
pathogenic effects of human ACPAs.
PMID- 25112159
TI - Relation between jumping to conclusions and cognitive functioning in people with
schizophrenia in contrast with healthy participants.
AB - 'Jumping to conclusions' (JTC) is a reasoning bias consisting of a tendency to
take a decision without having enough information about an event. It has been
related to the presence of delusions. The aim of the present study was to assess
the relationship between three tasks differing in complexity and concept which
assess JTC and cognitive functioning in a sample of people with schizophrenia and
healthy participants. We also assessed which cognitive variables, after
controlling for psychotic symptoms, explained the presence of JTC in each sample.
A total of 43 patients with schizophrenia and 57 healthy participants were
assessed with a cognition battery including executive function, verbal memory,
and IQ. JTC was assessed with three tasks (probability of 85:15; 60:40, and 60:40
with emotional component). Patients were also assessed on psychotic and affective
symptoms and the healthy participants on proneness to hallucinations and
delusion. The present study demonstrates a clear relationship between JTC and
cognitive functioning, especially in working memory, verbal memory, and cognitive
processing speed in people with schizophrenia and in healthy participants.
However no relationship was found in the emotional task of JTC. Hallucinations
(in people with schizophrenia) and proneness to hallucinations (in the healthy
participants) are related to JTC. Our results suggest that diverse psychological
interventions such as cognitive remediation, cognitive behavioral therapy and
meta-cognitive training might contribute to reducing JTC bias.
PMID- 25112158
TI - Disease and drug effects on internally-generated and externally-elicited
responses in first episode schizophrenia and psychotic bipolar disorder.
AB - Neurocognitive deficits are associated with most psychotic disorders, but may
differ across diagnosis and by treatment status. This ambiguity is partly
addressed in longitudinal pre/post treatment studies with first episode patients.
Antipsychotic-naive first-episode schizophrenia patients have shown intact
performance on a predictive saccade task that assesses simple motor learning,
spatial abilities, and response planning. After antipsychotic treatment, however,
schizophrenia patients performing this task show a selective impairment in the
accuracy of anticipatory responses, generated from learned internal
representations of the task stimulus. This finding is in line with other
observations of antipsychotic medication effects on frontostriatal systems,
particularly dorsolateral prefrontal cortex. We sought to replicate this
provocative finding with an independent sample of antipsychotic-naive first
episode schizophrenia patients and extend it by including a group of patients
with first episode bipolar disorder with psychosis (BDP). Matched healthy
controls were also studied in parallel. Schizophrenia patients demonstrated
intact performance pretreatment followed by impairment post-treatment for
accuracy of anticipatory responses, and worse accuracy was associated with higher
antipsychotic dose. BDP patients displayed saccade accuracy deficits before and
after treatment and had no correlation of performance and antipsychotic dose. The
findings suggest different neural alterations early in the course of each
psychotic disorder, and different vulnerabilities to antipsychotic treatment
effects between schizophrenia and BDP.
PMID- 25112160
TI - The Arcuate Fasciculus in auditory-verbal hallucinations: a meta-analysis of
diffusion-tensor-imaging studies.
AB - Auditory-verbal hallucinations (AVHs) are associated with an impaired
connectivity of large-scale networks. To examine the relationship between white
matter integrity and AVHs, we conducted a meta-analysis of diffusion-tensor
imaging studies that compared patients with schizophrenia and AVHs with matched
healthy controls (HCs). Five studies were retained gathering 256 DTI data points,
divided into AVHs (n=106) and HCs (n=150). The meta-analysis demonstrated a
reduced fractional anisotropy in the left Arcuate Fasciculus (AF) of
hallucinators (hg= -0.42; CI[-0.69,-0.16]; p<10(-3)). The current meta-analysis
confirmed disruptions of white matter integrity in the left AF bundle of
schizophrenia patients with AVHs.
PMID- 25112162
TI - Copper(II) coordination polymers with azide and bipyridine-based zwitterionic
carboxylate ligands: structures and magnetism.
AB - Two novel Cu(II) coordination polymers, [Cu4O(L(1))4(N3)2]n(ClO4)4n.3nH2O (1) and
[Cu7(L(2))2(N3)14]n (2), have been synthesized from two zwitterionic carboxylate
ligands, 1-carboxylatomethyl-4,4'-bipyridinium (L(1)) and 1-carboxylatomethyl
4,4'-dimethylenedipyridinium (L(2)). Compound 1 exhibits interpenetrated 3D
diamond networks in which the unusual MU4-O-centred tetrahedral Cu4 clusters with
peripheral 1,1-N3 and COO bridges are cross-linked by 4,4'-dipyridinium-1
methylene spacers. In compound 2, pentanuclear and dinuclear units with double
azide bridges are linked into a unique 2D layer by MU3-1,1,3-N3, (1,1-N3)(COO)
and the organic backbone of the zwitterionic ligand. Magnetic studies reveal that
compound 1 exhibits ferromagnetic coupling through (MU4-O)(1,1-N3) and
antiferromagnetic coupling through the MU4-O-only and (MU4-O)(COO)2 pathways.
Compound 2 exhibits ferromagnetic coupling within the (1,1-N3)2 bridged
polynuclear units and weak antiferromagnetic coupling through MU3-1,1,3-N3, and
(1,1-N3)(COO) between the units.
PMID- 25112161
TI - The nature and timing of social deficits in child and adolescent offspring of
parents with schizophrenia: preliminary evidence for precursors of negative
symptoms?
AB - Children with social dysfunction and a first-degree relative with schizophrenia
are at elevated risk for schizophrenia; however, the nature of this dysfunction
is unclear. It was hypothesized that familial high-risk (HR) children and
adolescents (n=17) would have social skill deficits relative to healthy controls
(HC; n=35). HR participants had a bimodal distribution of social skill scores
(47% excellent; 53% poor). HR participants had worse social skills, assertion and
empathy scores, suggesting possible developmental precursors to the social
amotivation domain of negative symptoms. Characterizing HR children's social
deficits could assist identification of those at risk for schizophrenia.
PMID- 25112163
TI - Gas sensing of SnO2 nanocrystals revisited: developing ultra-sensitive sensors
for detecting the H2S leakage of biogas.
AB - As a typical mode of energy from waste, biogas technology is of great interest to
researchers. To detect the trace H2S released from biogas, we herein demonstrate
a high-performance sensor based on highly H2S-sensitive SnO2 nanocrystals, which
have been selectively prepared by solvothermal methods using benzimidazole as a
mineralization agent. The sensitivity of as-obtained SnO2 sensor towards 5 ppm
H2S can reach up to 357. Such a technique based on SnO2 nanocrystals opens up a
promising avenue for future practical applications in real-time monitoring a
trace of H2S from the leakage of biogas.
PMID- 25112164
TI - Epidemiology of nasopharyngeal colonization by S. pneumoniae in Indian infants in
the first 2 years of life.
AB - BACKGROUND: Streptococcus pneumoniae is a leading cause of invasive disease in
developing countries like India. Although the 13 valent pneumococcal vaccine has
already been introduced in the country, there is very little epidemiological data
regarding S. pneumoniae colonization and antibiotic susceptibility in Indian
infants. METHODS: We studied serogroup/serotype (SGT) distribution and antibiotic
susceptibility pattern of S. pneumoniae in unvaccinated Indian infants by
performing monthly nasopharyngeal swabbing of a birth cohort for 2 years.
RESULTS: Colonization began soon after birth and was complete in the first year
of life in the majority of those colonized. Carriage rates increased during
winter (p<0.01) and in those with upper respiratory infection (URI) (p<0.01). The
most frequently (76.1%) isolated SGT were 19, 6, 15, 23, 9, 35 and 10. Vaccine
SGT accounted for 60.5% of all colonizers. Antibiotic resistance was maximum for
cotrimoxazole (94.3%) and least for erythromycin (11.2%) with no penicillin
resistance. Ten of the commonest SGT which cause invasive disease among Indian
infants comprised 46.9% of the colonizers. Serogroups 1, 5, 45 and 12 which cause
invasive disease in under-fives were not seen in this birth cohort in the first
year. CONCLUSIONS: S. pneumoniae colonization in Indian infants commences soon
after birth and chiefly occurs in the first year of life. The 13 valent vaccine
may protect against a little less than half the commonly seen invasive SGT of S.
pneumoniae.
PMID- 25112165
TI - Speech outcomes at age 5 and 10 years in unilateral cleft lip and palate after
one-stage palatal repair with minimal incision technique - a longitudinal
perspective.
AB - OBJECTIVES: To investigate speech outcomes in 5- and 10-year-old children with
unilateral cleft lip and palate (UCLP) treated according to minimal incision
technique (MIT) - a one-stage palatal method. METHODS: A retrospective,
longitudinal cohort study of a consecutive series of 69 patients born with UCLP,
treated with MIT (mean age 13 months) was included. Forty-two children (43%)
received a velopharyngeal flap; 12 before 5 years and another 18 before 10 years
of age. Cleft speech variables were rated from standardized audio recordings at 5
and 10 years of age, independently by three experienced, external speech-language
pathologists, blinded to the material. The prevalences of cleft speech
characteristics were determined, and inter- and intra-rater agreement calculated.
RESULTS: More than mild hypernasality, weak pressure consonants and perceived
incompetent velopharyngeal function were present in 19-22% of the children at 5
years, but improved to less than 5% at 10 years. However, audible nasal air
leakage, prevalent in 23% at 5 years, did not improve by age 10. Thirty percent
had frequent or almost always persistent compensatory articulation at 5 years,
and 6% at age 10. The general impression of speech improved markedly, from 57%
giving a normal impression at 5 years to 89% at 10 years. A high prevalence of
distorted/s/was found at both 5 and 10 years of age. CONCLUSIONS: A high
occurrence of speech deviances at 5 years of age after MIT was markedly reduced
at 10 years in this study of children with unilateral cleft lip and palate. The
high pharyngeal flap rate presumably accounted for the positive speech
development.
PMID- 25112166
TI - Pseudohypacusis in children: circumstances and diagnostic strategy.
AB - OBJECTIVES: The study attempts to specify the circumstances under which we should
pay attention to children's pseudohypacusis. It evaluates the methods used to
detect such cases and to determine hearing thresholds, according to the uni-or
bilateralism of hearing loss. The study finally deals with the future of children
diagnosed with pseudohypacusis. METHODS: The study was retrospective from January
1993 to November 2011 and prospective from December 2011 to April 2012. We
included all the children between 3 and 16 years who were diagnosed with
pseudohypacusis. We observed the reasons for them to consult, whether they had
already been tested or had treatment, and what kind of hearing loss they
displayed. All children were tested using standard pure tone audiometry and
speech audiometry. Depending on the first results, other tests were conducted.
They included transient evoked otoacoustic emissions (TEOEs), auditory brainstem
responses (ABR) and auditory steady state responses. Families were finally
contacted by phone over April 2012 in order to let them know about their child's
results. RESULTS: Fifty-four children were included: 19 boys and 35 girls, with
an average age of 10 year-old (+/-3). The simulated hearing loss (HL) was
bilateral (36), unilateral (18), of perception (37), moderate HL (33), cophosis
(5). Fifteen cases were linked to a family or personal history of hearing loss,
while 27 cases were due to important events like adoption, abuse, verbal
aggression, school problems. Before diagnosing a pseudohypacusis, 13 children had
had imaging studies, 3 had been treated with corticosteroids, and 5 had hearing
aids. Most of the time the presence of pseudohypacusis was suspected a
discrepancy between speech reception and air-conduction pure tone thresholds, as
shown by the medical test (answer on whispered voice). The diagnosis was
confirmed by ABR or TEOEs, except in cases where clinic was obvious. Then
family's patient and patient were reassured and informed. An audiological follow
up during either 6 months or 1 year was proposed, as well as a psychological
consultation. CONCLUSION: Complementary examinations have to be performed to rule
out a pseudohypacusis case before suggesting an invasive or expensive treatment
(surgery or hearing aids) of children.
PMID- 25112167
TI - A test protocol for assessing the hearing status of students with special needs.
AB - OBJECTIVES: Individuals with disabilities are often reported to have a high
prevalence of undetected hearing disorders/loss, but there is no standardized
hearing test protocol for this population. The purposes of this study were (1) to
examine the hearing status of students with special needs in Taiwan, and (2) to
investigate the use of an on-site hearing test protocol that would adequately
detect hearing problems in this population and reduce unnecessary referrals for
off-site follow-up services. METHODS: A total of 238 students enrolled in two
schools for special education and one habilitation center participated in the
study. Most students had intellectual disabilities and some also had additional
syndromes or disorders. A hearing screening protocol including otoscopy,
tympanometry, and distortion product otoacoustic emissions was administered to
examine students' outer, middle, and inner ear functions, respectively. Pure tone
tests were then administered as an on-site follow-up for those who failed or
could not be tested using the screening protocol. RESULTS: Only 32.4% of students
passed. When administered alone, the referral rate of otoscopy, tympanometry, and
otoacoustic emissions were 38.7%, 46.0%, and 48.5%, respectively. The integration
of these subtests revealed 52.1% of students needed follow-up services, 11.8%
could not be tested, 2.5% had documented hearing loss, and 1.3% needed to be
monitored because of negative middle ear pressure. The inclusion of pure tone
audiometry increased the passing rate by 9.9% and provided information on hearing
sensitivity for an additional 8.6% of students. CONCLUSION: Hearing assessments
and regular hearing screening should be provided as an integral part of health
care services for individuals with special needs because of high occurrences of
excessive cerumen, middle ear dysfunction, and sensorineural hearing loss. The
training of care-givers and teachers of students with special needs is encouraged
so that they can help identify hearing problems and reduce the negative impact of
hearing disorders and hearing loss. The screening protocol needs to include
subtests that examine the status of different parts of their auditory system. The
addition of pure tone audiometry as an on-site follow-up tool reduced the rate of
off-site referrals and provided more information on hearing sensitivity.
PMID- 25112169
TI - The roles of the Q (q) wave in lead I and QRS frontal axis for diagnosing loss of
left ventricular capture during cardiac resynchronization therapy.
AB - INTRODUCTION: Loss of left ventricular (LV) capture may lead to deterioration of
heart failure in patients with cardiac resynchronization therapy (CRT).
Recognition of loss of LV capture in time is important in clinical practice.
METHODS AND RESULTS: A total of 422 electrocardiograms were acquired and analyzed
from 53 CRT patients at 8 different pacing settings (LV only, right ventricle
[RV] only, biventricular [BV] pacing with LV preactivation of 60, 40, 20, and 0
milliseconds and RV preactivation of 20 and 40 milliseconds). A modified Ammann
algorithm by adding a third step-presence of Q (q, or QS) wave-to the original 2
step Ammann algorithm and a QRS axis shift method were devised to identify the
loss of LV capture. The accuracy of modified Ammann algorithm was significantly
higher than that of Ammann algorithm (78.9% vs. 69.1%, P < 0.001). The accuracy
of the axis shift method was 66.4%, which was significantly lower than the
modified Ammann algorithm (P < 0.001) and similar to the original one (P =
0.412). However, in the ECGs with QRS axis shift, 96.8% were correctly
classified. LV preactivation or simultaneous BV activation and LV lead positioned
in nonposterior or noninferior wall could elevate the accuracies of the modified
Ammann algorithm and the QRS axis shift method. CONCLUSIONS: The accuracy of the
modified Ammann algorithm is greatly improved. The QRS axis shift method can help
diagnose LV capture. The LV preactivation, or simultaneous BV activation and LV
lead positioned in nonposterior or noninferior wall can increase the diagnostic
power of the modified Ammann algorithm and QRS axis shift method.
PMID- 25112168
TI - De novo transcriptome sequencing and digital gene expression analysis predict
biosynthetic pathway of rhynchophylline and isorhynchophylline from Uncaria
rhynchophylla, a non-model plant with potent anti-alzheimer's properties.
AB - BACKGROUND: The major medicinal alkaloids isolated from Uncaria rhynchophylla
(gouteng in chinese) capsules are rhynchophylline (RIN) and isorhynchophylline
(IRN). Extracts containing these terpene indole alkaloids (TIAs) can inhibit the
formation and destabilize preformed fibrils of amyloid beta protein (a
pathological marker of Alzheimer's disease), and have been shown to improve the
cognitive function of mice with Alzheimer-like symptoms. The biosynthetic
pathways of RIN and IRN are largely unknown. RESULTS: In this study, RNA
sequencing of pooled Uncaria capsules RNA samples taken at three developmental
stages that accumulate different amount of RIN and IRN was performed. More than
50 million high-quality reads from a cDNA library were generated and de novo
assembled. Sequences for all of the known enzymes involved in TIAs synthesis were
identified. Additionally, 193 cytochrome P450 (CYP450), 280 methyltransferase and
144 isomerase genes were identified, that are potential candidates for enzymes
involved in RIN and IRN synthesis. Digital gene expression profile (DGE) analysis
was performed on the three capsule developmental stages, and based on genes
possessing expression profiles consistent with RIN and IRN levels; four CYP450s,
three methyltransferases and three isomerases were identified as the candidates
most likely to be involved in the later steps of RIN and IRN biosynthesis.
CONCLUSION: A combination of de novo transcriptome assembly and DGE analysis was
shown to be a powerful method for identifying genes encoding enzymes potentially
involved in the biosynthesis of important secondary metabolites in a non-model
plant. The transcriptome data from this study provides an important resource for
understanding the formation of major bioactive constituents in the capsule
extract from Uncaria, and provides information that may aid in metabolic
engineering to increase yields of these important alkaloids.
PMID- 25112170
TI - Room-temperature sensor based on surface-enhanced Raman spectroscopy.
AB - As reported in the literature, several factors, such as scattering cross
sections, polarisability and wavelength suitability, contribute to increased SERS
enhancement. In general, the advantage of surface-enhanced Raman scattering
(SERS)-active Ag nanoparticles (NPs) is their higher SERS enhancement over Au NPs
because the molar extinction coefficient of the Ag NPs is the highest of its kind
among metals. Nevertheless, the corresponding SERS-active hot spots on Au are of
inherently greater stability than on Ag. In this work, innovative temperature
sensors based on SERS-active Au and Ag substrates prepared by sonoelectrochemical
deposition-dissolution cycles (SEDDCs) are first reported. The SERS intensity of
the model probe molecules of Rhodamine 6G (R6G) adsorbed on a SERS-active Ag
substrate is monotonically increased from 25 to 50 degrees C. Moreover, this
temperature-dependent intensity is linear with a slope of ca. 430 cps per
degrees C between 25 to 45 degrees C. In addition, the reversibility and
reusability of the developed temperature sensors are evaluated after the R6G
adsorbed sensors are alternately exposed to the temperatures of 25 and 45
degrees C in a sealed chamber. After every five cycles, the SERS spectra of
treated substrates were recorded and compared with those of the as-prepared
substrates. Experimental results indicate that SERS enhancement capability is
mostly reversible based on 90% intensity of the Raman signal being maintained for
the SERS-active Au substrate after 25 cycles (only 15 cycles for the Ag
substrate).
PMID- 25112172
TI - Steep drop in hematocrit of sheep undergoing sedation with acepromazine-diazepam
and epidural injections of ketamine, ketamine-morphine or ketamine-xylazine.
PMID- 25112171
TI - Asymmetric transverse control of maxillary dentition with two midpalatal
orthodontic miniscrews.
AB - There have been several orthodontic modalities for maxillary transverse control
with most addressing symmetric control. The asymmetric transverse control of
maxillary dentition is challenging to orthodontists due to the lack of certain
modalities and possible dental side effects. Skeletal anchorages provide
biomechanics without orthodontic side effects, but reports of their utilization
for transverse control of maxillary dentition are scarce. The purpose of this
article is to introduce a novel method utilizing two midpalatal orthodontic
miniscrews and a connecting wire system for the asymmetric transverse control of
maxillary dentition. Records of two patients consecutively treated with this
system are reported, and the related biomechanical considerations are presented.
PMID- 25112173
TI - Clinical utility and validity of minoxidil response testing in androgenetic
alopecia.
AB - Clinical response to 5% topical minoxidil for the treatment of androgenetic
alopecia (AGA) is typically observed after 3-6 months. Approximately 40% of
patients will regrow hair. Given the prolonged treatment time required to elicit
a response, a diagnostic test for ruling out nonresponders would have significant
clinical utility. Two studies have previously reported that sulfotransferase
enzyme activity in plucked hair follicles predicts a patient's response to
topical minoxidil therapy. The aim of this study was to assess the clinical
utility and validity of minoxidil response testing. In this communication, the
present authors conducted an analysis of completed and ongoing studies of
minoxidil response testing. The analysis confirmed the clinical utility of a
sulfotransferase enzyme test in successfully ruling out 95.9% of nonresponders to
topical minoxidil for the treatment of AGA.
PMID- 25112174
TI - Awareness of surgical costs: a multicenter cross-sectional survey.
AB - BACKGROUND: Resource scarcity continues to be an important problem in modern
surgical practice. Studies in North America and Europe have found that medical
professionals have limited understanding of the costs of medical care. No cost
awareness studies have been undertaken in Australasia or specifically focusing on
the surgical team. This study determined the cost of a range of commonly used
diagnostic tests, procedures, and hospital resources associated with care of the
surgical patient. The surgical teams' awareness of these costs was then assessed
in a multicenter cross-sectional survey. METHODS: In total, 14 general surgical
consultants, 14 registrars, and 25 house officers working in three New Zealand
hospitals were asked to estimate the costs of 14 items commonly associated with
patient care. Cost estimations were considered correct if within 25% plus or
minus of the actual cost. Accuracy was assessed by calculating the median, mean,
and absolute percentage discrepancy. RESULTS: A total of 57 surveys were
completed. Of which, four were incomplete and were not included in the analysis.
Cost awareness was generally poor, and members of the surgical team were rarely
able to estimate the costs to within 25%. The mean absolute percentage error was
0.87 (95% CI: 0.58-1.18) and underestimates were most common. There was no
significant difference in estimate accuracy between consultants, registrars, or
house officers, or between consultants working in both public/private practice
compared with those working in public practice alone. CONCLUSION: There is poor
awareness of surgical costs among consultant surgeons, registrars, and junior
physicians working in Australasia.
PMID- 25112176
TI - The paradox of atrial fibrillation in African Americans.
AB - The reported lower prevalence and incidence of atrial fibrillation (AF) despite
the higher prevalence of AF risk factors in African Americans compared to
Caucasian whites has been referred to as the paradox of AF in African Americans.
In this report we highlight this paradox and address potential explanations using
data from several US populations studies. These possible explanations include
limited methodology to detect AF patterns that are harder to detect (e.g.
paroxysmal/intermittent AF or atrial flutter) coupled with the possibility of
African Americans having more of these patterns, differential access to health
care with African Americans having less access and subsequently less detected AF,
survival bias with Caucasian whites living longer and subsequently having more
AF, and finally differential impact of AF risk factors with Caucasian whites
being more affected or African Americans less affected by AF risk factors whether
this is genetically determined or via other unknown predispositions.
PMID- 25112177
TI - Antagonism of D1/D5 receptors prevents long-term depression (LTD) and learning
facilitated LTD at the perforant path-dentate gyrus synapse in freely behaving
rats.
AB - Hippocampal synaptic plasticity, in the form of long-term potentiation (LTP) and
long-term depression (LTD), enables spatial memory formation, whereby LTP and LTD
are likely to contribute different elements to the resulting spatial
representation. Dopamine, released from the ventral tegmental area particularly
under conditions of reward, acts on the hippocampus, and may specifically
influence the encoding of information into long-term memory. The dentate gyrus
(DG), as the "gateway" to the hippocampus is likely to play an important role in
this process. D1/D5 dopamine receptors are importantly involved in the regulation
of synaptic plasticity thresholds in the CA1 region of the hippocampus and
determine the direction of change in synaptic strength that occurs during novel
spatial learning. Here, we explored whether D1/D5-receptors influence LTD that is
induced in the DG following patterned afferent stimulation of the perforant path
of freely behaving adult rats, or influence LTD that occurs in association with
spatial learning. We found that LTD that is induced by afferent stimulation, and
LTD that is facilitated by learning about novel landmark configurations, were
both prevented by D1/D5-receptor antagonism, whereas agonist activation of the
D1/D5-receptor had no effect on basal tonus or short-term depression. Other
studies have reported that in the DG, D1/D5-receptor agonism or antagonism do not
affect LTP, but agonism prevents depotentiation. These findings suggest that the
dopaminergic system, acting via D1/D5-receptors, influences information gating by
the DG and modulates the direction of change in synaptic strength that underlies
information storage in this hippocampal substructure. Information encoded by
robust forms of LTD is especially dependent on D1/D5-receptor activation. Thus,
dopamine acting on D1/D5-receptors is likely to support specific experience
dependent encoding, and may influence the content of hippocampal representations
of experience.
PMID- 25112175
TI - Tryptophan supplementation and postoperative delirium--a randomized controlled
trial.
AB - OBJECTIVES: To determine whether the postoperative administration of tryptophan
would be beneficial for elderly adults undergoing surgery who are at risk of
developing postoperative delirium. DESIGN: Randomized, double-blind, placebo
controlled trial. SETTING: Denver Veterans Affairs Medical Center. PARTICIPANTS:
Individuals aged 60 and older undergoing major elective operations requiring a
postoperative intensive care unit (ICU) admission (n = 325). INTERVENTION: L
tryptophan, 1 g orally three times a day or placebo was started after surgery and
continued for up to 3 days postoperatively. MEASUREMENTS: Delirium and its motor
subtypes were measured using the Confusion Assessment Method-Intensive Care Unit
(CAM-ICU) and the Richmond Agitation and Sedation Scale. The primary outcome for
between-group comparison was the incidence of excitatory (mixed and hyperactive)
postoperative delirium. The secondary outcomes for comparison were the incidence
and duration of overall postoperative delirium. RESULTS: The overall incidence of
postoperative delirium was 39% (95% confidence interval = 34-44%) (n = 116).
Seventeen percent of participants in the tryptophan group and 9% in the placebo
group had excitatory delirium (P = .18), and the duration of excitatory delirium
was 3.3 +/- 1.7 days for tryptophan and 3.1 +/- 1.9 days for placebo (P = .74).
Forty percent of participants in the tryptophan group and 37% in the placebo
group had overall delirium (P = .60), and the duration of overall delirium was
2.9 +/- 1.8 days for tryptophan and 2.4 +/- 1.6 days for placebo (P = .17).
CONCLUSION: Postoperative tryptophan supplementation in older adults undergoing
major elective operations requiring postoperative ICU admission did not reduce
the incidence or duration of postoperative excitatory delirium or overall
delirium.
PMID- 25112178
TI - [Treatment of giant acoustic neuromas].
AB - INTRODUCTION AND OBJECTIVES: To analyze the treatment modality and outcome of a
series of patients with giant acoustic neuromas, a particular type of tumour
characterised by their size (extracanalicular diameter of 4cm or more) and high
morbidity and mortality. MATERIALS AND METHODS: This was a retrospective
unicentre study of patients with acoustic neuromas treated in a period of 12
years. In our institutional series of 108 acoustic neuromas operated on during
that period, we found 13 (12%) cases of giant acoustic neuromas. We reviewed the
available data of these cases, including presentation and several clinical,
anatomical, and microsurgical aspects. RESULTS: All patients were operated on by
the same neurosurgeon and senior author (EU) using the suboccipital retrosigmoid
approach and complete microsurgical removal was achieved in 10 cases. In one
case, near total removal was deliberately performed, in another case a CSF shunt
was placed as the sole treatment measure, and in the remaining case no direct
treatment was given. One patient died in the immediate postoperative period. One
year after surgery, 4 patients showed facial nerve function of iii or more in the
House-Brackman scale. CONCLUSIONS: The 4 most important prognostic
characteristics of giant acoustic neuromas are size, adhesion to surrounding
structures, consistency and vascularity. Only the first of these is evident in
neuroimaging. Giant acoustic neuromas are characterised by high morbidity at
presentation as well as after treatment. Nevertheless, the objective of complete
microsurgical removal with preservation of cranial nerve function is attainable
in some cases through the suboccipital retrosigmoid approach.
PMID- 25112179
TI - Vitamin D deficiency in minority populations.
AB - OBJECTIVE: Black and Hispanic individuals synthesize less vitamin D per unit of
sun exposure than white individuals. The relationship between UV radiation and
vitamin D insufficiency in minorities has not been well explored. DESIGN:
Prospective cohort study. SETTING: Using the National Health and Nutrition
Examination Survey, we obtained serum vitamin D levels for non-Hispanic Whites,
Hispanics and non-Hispanic Blacks aged >=18 years from 2000-2006. We linked these
data with the average monthly solar UV index by census tract and data on sun
exposure, vitamin D supplementation, health and demographics. We used
multivariable regression analyses to assess vitamin D deficiency (<15 ng/ml) and
insufficiency (<20 ng/ml) in January (when the UV index was lowest) by
race/ethnicity and geography. SUBJECTS: Adults (n 14,319) aged >=18 years.
RESULTS: A 1-point increase in the UV index was associated with a 0.51 ng/ml
increase in vitamin D (95% CI 0.35, 0.67 ng/ml; P<0.001). Non-Hispanic Black race
and Hispanic ethnicity were associated with a 7.47 and 3.41 ng/ml decrease in
vitamin D, respectively (both P<0.001). In January, an estimated 65.4% of non
Hispanic Blacks were deficient in vitamin D, compared with 28.9% of Hispanics and
14.0% of non-Hispanic Whites. An estimated 84.2% of non-Hispanic Blacks were
insufficient in vitamin D v. 56.3% of Hispanics and 34.8% of non-Hispanic Whites.
More non-Hispanic Blacks were estimated to be deficient in vitamin D in January
in the highest UV index quartile than were non-Hispanic Whites in the lowest UV
index quartile (60.2% v. 25.7%). CONCLUSIONS: Wintertime vitamin D insufficiency
is pervasive among minority populations, and not uncommon among non-Hispanic
Whites.
PMID- 25112181
TI - Microfluidic geometric metering-based multi-reagent mixture generator for robust
live cell screening array.
AB - Microfluidic live cell arrays with integrated concentration gradient or mixture
generators have been utilized in screening cellular responses to various
biomolecular cues. Microfluidic network-based gradient generators that can create
concentration gradients by repeatedly splitting and mixing different solutions
using networks of serpentine channels are commonly used. However, in this method
the generation of concentration gradients relies on the continuous flow of sample
solutions at optimized flow rates, which poses challenges in maintaining the
pressure and flow stability throughout the entire assay period. Here we present a
microfluidic live cell screening array with an on-demand multi-reagent mixture
generator where the mixing ratios, thus generated concentrations, are hard-wired
into the chip itself through a geometric metering method. This platform showed
significantly improved robustness and repeatability in generating concentration
gradients of fluorescent dyes (average coefficient of variance C.V. = 9 %)
compared to the conventional network-based gradient generators (average C.V. = 21
%). In studying the concentration dependent effects of the environmental toxicant
3-methylcholanthrene (3MC) on the activation of cytochrome P450 1A1 (Cyp 1A1)
enzyme in H4IIE rat hepatoma cells, statistical variation of the Cyp 1A1 response
was significantly lower (C.V. = 5 %) when using the developed mixture generator
compared to that using the conventional gradient generator (C.V. = 12 %).
Reduction in reagent consumption by 12-times was also achieved. This robust,
accurate, and scalable multi-reagent mixture generator integrated with a cell
culture array as a live cell assay platform can be readily implemented into
various screening applications where repeatability, robustness, and low reagent
consumptions over long periods of assay time are of importance.
PMID- 25112180
TI - The important ergot alkaloid intermediate chanoclavine-I produced in the yeast
Saccharomyces cerevisiae by the combined action of EasC and EasE from Aspergillus
japonicus.
AB - BACKGROUND: Ergot alkaloids are a group of highly bioactive molecules produced by
a number of filamentous fungi. These compounds have been intensely studied for
decades, mainly due to their deleterious effects in contaminated food and feeds,
but also for their beneficial pharmaceutical and agricultural applications.
Biosynthesis of ergot alkaloids goes via the common intermediate chanoclavine-I,
and studies of the key enzymes, EasE and EasC, involved in chanoclavine-I
formation, have relied on gene complementation in fungi, whereas further
characterization has been hampered by difficulties of poor EasE protein
expression. In order to facilitate the study of ergot alkaloids, and eventually
move towards commercial production, the early steps of the biosynthetic pathway
were reconstituted in the unicellular yeast Saccharomyces cerevisiae. RESULTS:
The genomic sequence from an ergot alkaloid producer, Aspergillus japonicus, was
used to predict the protein encoding sequences of the early ergot alkaloid
pathway genes. These were cloned and expressed in yeast, resulting in de novo
production of the common intermediate chanoclavine-I. This allowed further
characterization of EasE and EasC, and we were able to demonstrate how the N
terminal ER targeting signal of EasE is crucial for activity in yeast. A
putative, peroxisomal targeting signal found in EasC was shown to be
nonessential. Overexpression of host genes pdi1 or ero1, associated with
disulphide bond formation and the ER protein folding machinery, was shown to
increase chanoclavine-I production in yeast. This was also the case when
overexpressing host fad1, known to be involved in co-factor generation.
CONCLUSIONS: A thorough understanding of the enzymatic steps involved in ergot
alkaloid formation is essential for commercial production and exploitation of
this potent compound class. We show here that EasE and EasC are both necessary
and sufficient for the production of chanoclavine-I in yeast, and we provide
important new information about the involvement of ER and protein folding for
proper functional expression of EasE. Moreover, by reconstructing the
chanoclavine-I biosynthetic pathway in yeast we demonstrate the advantage and
potential of this host, not only as a convenient model system, but also as an
alternative cell factory for ergot alkaloid production.
PMID- 25112182
TI - Drinking from the Holy Grail: analysis of whole-genome sequencing from the
Genetic Analysis Workshop 18.
AB - The Genetic Analysis Workshops distribute real and simulated human genetic data
to allow the development and comparison of methods to detect genetic variants and
genes related to biological traits; the results are then presented and discussed
at a biennial meeting. The data made available for Genetic Analysis Workshop 18
(GAW18) included whole-genome sequence data for odd-numbered autosomes from 20
large Mexican American pedigrees selected through probands with type 2 diabetes.
Real and simulated blood pressure phenotype data were provided to allow the
comparison of methods to detect variants and genes associated with blood
pressure. Some of the complexity present in the data includes related
individuals, repeated quantitative trait outcomes, covariates, medication
effects, pharmacokinetic effects, missing data, admixed population, and imputed
genotypes. A wide range of analytic approaches were applied to the data.
Contributions that focused only on a subset of up to 155 unrelated subjects from
the pedigrees were faced with low power. One recommendation for future analysis
is the use of the provided null phenotype to allow comparison of type I error
across methods. Collaboration between statistical geneticists and molecular
biologists or bioinformaticians would provide helpful input to place variants in
genes for gene-based association tests.
PMID- 25112183
TI - Methods for collapsing multiple rare variants in whole-genome sequence data.
AB - Genetic Analysis Workshop 18 provided whole-genome sequence data in a pedigree
based sample and longitudinal phenotype data for hypertension and related traits,
presenting an excellent opportunity for evaluating analysis choices. We summarize
the nine contributions to the working group on collapsing methods, which
evaluated various approaches for the analysis of multiple rare variants. One
contributor defined a variant prioritization scheme, whereas the remaining eight
contributors evaluated statistical methods for association analysis. Six
contributors chose the gene as the genomic region for collapsing variants,
whereas three contributors chose nonoverlapping sliding windows across the entire
genome. Statistical methods spanned most of the published methods, including well
established burden tests, variance-components-type tests, and recently developed
hybrid approaches. Lesser known methods, such as functional principal components
analysis, higher criticism, and homozygosity association, and some newly
introduced methods were also used. We found that performance of these methods
depended on the characteristics of the genomic region, such as effect size and
direction of variants under consideration. Except for MAP4 and FLT3, the
performance of all statistical methods to identify rare casual variants was
disappointingly poor, providing overall power almost identical to the type I
error. This poor performance may have arisen from a combination of (1) small
sample size, (2) small effects of most of the causal variants, explaining a small
fraction of variance, (3) use of incomplete annotation information, and (4)
linkage disequilibrium between causal variants in a gene and noncausal variants
in nearby genes. Our findings demonstrate challenges in analyzing rare variants
identified from sequence data.
PMID- 25112184
TI - Value of Mendelian laws of segregation in families: data quality control,
imputation, and beyond.
AB - When analyzing family data, we dream of perfectly informative data, even whole
genome sequences (WGSs) for all family members. Reality intervenes, and we find
that next-generation sequencing (NGS) data have errors and are often too
expensive or impossible to collect on everyone. The Genetic Analysis Workshop 18
working groups on quality control and dropping WGSs through families using a
genome-wide association framework focused on finding, correcting, and using
errors within the available sequence and family data, developing methods to infer
and analyze missing sequence data among relatives, and testing for linkage and
association with simulated blood pressure. We found that single-nucleotide
polymorphisms, NGS data, and imputed data are generally concordant but that
errors are particularly likely at rare variants, for homozygous genotypes, within
regions with repeated sequences or structural variants, and within sequence data
imputed from unrelated individuals. Admixture complicated identification of
cryptic relatedness, but information from Mendelian transmission improved error
detection and provided an estimate of the de novo mutation rate. Computationally,
fast rule-based imputation was accurate but could not cover as many loci or
subjects as more computationally demanding probability-based methods.
Incorporating population-level data into pedigree-based imputation methods
improved results. Observed data outperformed imputed data in association testing,
but imputed data were also useful. We discuss the strengths and weaknesses of
existing methods and suggest possible future directions, such as improving
communication between data collectors and data analysts, establishing thresholds
for and improving imputation quality, and incorporating error into imputation and
analytical models.
PMID- 25112185
TI - Complex pedigrees in the sequencing era: to track transmissions or decorrelate?
AB - Next-generation sequencing (NGS) studies are becoming commonplace, and the NGS
field is continuing to develop rapidly. Analytic methods aimed at testing for the
various roles that genetic susceptibility plays in disease are also rapidly being
developed and optimized. Studies that incorporate large, complex pedigrees are of
particular importance because they provide detailed information about inheritance
patterns and can be analyzed in a variety of complementary ways. The nine
contributions from our Genetic Analysis Workshop 18 working group on family-based
tests of association for rare variants using simulated data examined analytic
methods for testing genetic association using whole-genome sequencing data from
20 large pedigrees with 200 phenotype simulation replicates. What distinguishes
the approaches explored is how the complexities of analyzing familial genetic
data were handled. Here, we explore the methods that either harness inheritance
patterns and transmission information or attempt to adjust for the correlation
between family members in order to utilize computationally and conceptually
simpler statistical testing procedures. Although directly comparing these two
classes of approaches across contributions is difficult, we note that the two
classes balance robustness to population stratification and computational
complexity (the transmission-based approaches) with simplicity and increased
power, assuming no population stratification or proper adjustment for it
(decorrelation approaches).
PMID- 25112186
TI - Testing genetic association with rare and common variants in family data.
AB - With the advance of next-generation sequencing technologies in recent years, rare
genetic variant data have now become available for genetic epidemiology studies.
For family samples, however, only a few statistical methods for association
analysis of rare genetic variants have been developed. Rare variant approaches
are of great interest, particularly for family data, because samples enriched for
trait-relevant variants can be ascertained and rare variants are putatively
enriched through segregation. To facilitate the evaluation of existing and new
rare variant testing approaches for analyzing family data, Genetic Analysis
Workshop 18 (GAW18) provided genotype and next-generation sequencing data and
longitudinal blood pressure traits from extended pedigrees of Mexican American
families from the San Antonio Family Study. Our GAW18 group members analyzed real
and simulated phenotype data from GAW18 by using generalized linear mixed-effects
models or principal components to adjust for familial correlation or by testing
binary traits using a correction factor for familial effects. With one exception,
approaches dealt with the extended pedigrees in their original state using
information based on the kinship matrix or alternative genetic similarity
measures. For simulated data our group demonstrated that the family-based kernel
machine score test is superior in power to family-based single-marker or burden
tests, except in a few specific scenarios. For real data three contributions
identified significant associations. They substantially reduced the number of
tests before performing the association analysis. We conclude from our real data
analyses that further development of strategies for targeted testing or more
focused screening of genetic variants is strongly desirable.
PMID- 25112187
TI - Summary of results and discussions from the gene-based tests group at Genetic
Analysis Workshop 18.
AB - I present a summary of the results and discussions held within the working group
on gene-based tests at Genetic Analysis Workshop 18 (GAW18). The main focus of
interest in our working group was modeling the action of combinations or "groups"
of genetic variants, with a group of variants most often defined as a set of
single-nucleotide polymorphisms lying within a known gene. Some contributions
investigated the performance of previously proposed methods (particularly rare
variant collapsing or burden-type methods) for addressing this question, applied
to the GAW18 data, and other contributions developed novel approaches and
addressed novel questions. Most approaches were successful in detecting
significant effects at MAP4 in the simulated data. No other genetic effects were
consistently detected across different analyses. Low power was noted,
particularly for those methods that restricted analysis to purely the subset of
unrelated individuals.
PMID- 25112188
TI - Population-based association and gene by environment interactions in Genetic
Analysis Workshop 18.
AB - In the past decade, genome-wide association studies have been successful in
identifying genetic loci that play a role in many complex diseases. Despite this,
it has become clear that for many traits, investigation of single common variants
does not give a complete picture of the genetic contribution to the phenotype.
Therefore a number of new approaches are currently being investigated to further
the search for susceptibility loci or regions. We summarize the contributions to
Genetic Analysis Workshop 18 (GAW18) that concern this search using methods for
population-based association analysis. Many of the members of our GAW18 working
group made use of data types that have only recently become available through the
use of next-generation sequencing technologies, with many focusing on the
investigation of rare variants instead of or in combination with common variants.
Some contributors used a haplotype-based approach, which to date has been used
relatively infrequently but may become more important for analyzing rare variant
association data. Others analyzed gene-gene or gene-environment interactions,
where novel statistical approaches were needed to make the best use of the
available information without requiring an excessive computational burden. GAW18
provided participants with the chance to make use of state-of-the-art data,
statistical techniques, and technology. We report here some of the experiences
and conclusions that were reached by workshop participants who analyzed the GAW18
data as a population-based association study.
PMID- 25112189
TI - Local and global ancestry inference and applications to genetic association
analysis for admixed populations.
AB - Genetic association studies in recently admixed populations offer exciting
opportunities to identify novel variants underlying phenotypic diversity. At the
same time, genetic heterogeneity resulting from population admixture has to be
accounted for to ensure validity of association tests. The whole-genome sequence
data and the genome-wide single-nucleotide polymorphism chip data for Mexican
American individuals provided by Genetic Analysis Workshop 18 (GAW18) presents a
unique opportunity to evaluate and compare methods for the statistical analysis
of admixed genetic data. We summarize here the five contributions from the GAW18
working group on admixture mapping and adjusting for admixture. Although group
members considered a variety of research topics, the general theme was inference
and consideration of ancestry admixture in genetic analyses. The topics
considered can be grouped into three categories: (1) global and local ancestry
inference and estimation, (2) association and admixture mapping, and (3) genotype
imputation in admixed samples. We describe the approaches that were used and the
most relevant findings from each contribution. We also provide insight into the
strengths and limitations of the state-of-the-art methods considered for genetic
analyses in admixed populations.
PMID- 25112191
TI - Multivariate analyses of blood pressure related phenotypes in a longitudinal
framework: insights from Genetic Analysis Workshop 18.
AB - Our working group studied methods for joint analyses of multiple phenotypes using
the data provided by Genetic Analysis Workshop 18. Two data sets were available:
one containing genotypes obtained from a real human whole-genome sequencing study
along with longitudinal measurements on systolic and diastolic blood pressure,
age, sex, medication use, and tobacco smoking; and the other a simulated data set
using the same set of genotypes and phenotype structure as the real data set. The
nine sets of investigators in our working group focused on the statistical
challenges posed by association analyses of multivariate phenotypes; they applied
a wide spectrum of statistical methods, such as linear mixed models, copula
models, and semiparametric regression models for simultaneous analyses of
longitudinal data on the two blood pressure phenotypes at the genome-wide level.
In this report, we discuss the various strategies explored by the different
investigators whose common goal was improving the power to detect association
with multivariate phenotypes.
PMID- 25112190
TI - Genetic prediction in the Genetic Analysis Workshop 18 sequencing data.
AB - High-throughput sequencing data can be used to predict phenotypes from genotypes,
and this corresponds to establishing a prognostic model. In extended pedigrees
the relatedness of subjects provides additional information so that genetic
values, fixed or random genetic components, and heritability can be estimated. At
the Genetic Analysis Workshop 18, the working group on genetic prediction dealt
with both establishing a prognostic model and, in one contribution, comparing
standard logistic regression with robust logistic regression in a sample of
unrelated affected or unaffected individuals. Results of both logistic regression
approaches were similar. All other contributions to this group used extended
family data, in general using the quantitative trait blood pressure. The
individual contributions varied in several important aspects, such as the
estimation of the kinship matrix and the estimation method. Contributors chose
various approaches for model validation, including different versions of cross
validation or within-family validation. Within-family validation included model
building in the upper generations and validation in later generations. The choice
of the statistical model and the computational algorithm had substantial effects
on computation time. If decorrelation approaches were applied, the computational
burden was substantially reduced. Some software packages estimated negative
eigenvalues, although eigenvalues of correlation matrices should be non-negative.
Most statistical models and software packages have been developed for
experimental crosses and planned breeding programs. With their specialized
pedigree structures, they are not sufficiently flexible to accommodate the
variability of human pedigrees in general, and improved implementations are
required.
PMID- 25112192
TI - Longitudinal data analysis in genome-wide association studies.
AB - Genome-wide association studies have led to the discovery of thousands of
susceptibility genetic variants (typically single-nucleotide polymorphisms
[SNPs]) for a wide range of complex diseases and traits commonly measured at a
single point in time. Although many novel genotype-phenotype associations have
been identified and successfully replicated using cross-sectionally measured
phenotypes, there is growing interest in the study of longitudinally measured
phenotypes because these allow for the study of the natural trajectory of traits
and disease progression. However, there are several challenges with analysis and
interpretation of longitudinal data. Here, we summarize the methods and
strategies proposed and applied in genome-wide association studies of blood
pressure related phenotypes made available through Genetic Analysis Workshop 18
(GAW18). The investigators considered methods that incorporated correlation
across time points and familial relatedness among the individuals into their
studies and compared their approaches with single-time-point analysis using
baseline data. Some of the studies used unrelated individuals; some also used the
simulated data provided by the GAW18 organizers to assess type I error and power
of their approach in detecting true associations.
PMID- 25112193
TI - Longitudinal data analysis for genetic studies in the whole-genome sequencing
era.
AB - The analysis of whole-genome sequence (WGS) data using longitudinal phenotypes
offers a potentially rich resource for the examination of the genetic variants
and their covariates that affect complex phenotypes over time. We summarize eight
contributions to the Genetic Analysis Workshop 18, which applied a diverse array
of statistical genetic methods to analyze WGS data in combination with data from
genome-wide association studies (GWAS) from up to four different time points on
blood pressure phenotypes. The common goal of these analyses was to develop and
apply appropriate methods that utilize longitudinal repeated measures to
potentially increase the analytic efficiency of WGS and GWAS data. These diverse
methods can be grouped into two categories, based on the way they model
dependence structures: (1) linear mixed-effects (LME) models, where the random
effect terms in the linear models are used to capture the dependence structures;
and (2) variance-components models, where the dependence structures are
constructed directly based on multiple components of variance-covariance matrices
for the multivariate Gaussian responses. Despite the heterogeneous nature of
these analytical methods, the group came to the following conclusions: (1) the
use of repeat measurements can gain power to identify variants associated with
the phenotype; (2) the inclusion of family data may correct genotyping errors and
allow for more accurate detection of rare variants than using unrelated
individuals only; and (3) fitting mixed-effects and variance-components models
for longitudinal data presents computational challenges. The challenges and
computational burden demanded by WGS data were addressed in the eight
contributions.
PMID- 25112194
TI - Applications of machine learning and data mining methods to detect associations
of rare and common variants with complex traits.
AB - Machine learning methods (MLMs), designed to develop models using high
dimensional predictors, have been used to analyze genome-wide genetic and genomic
data to predict risks for complex traits. We summarize the results from six
contributions to our Genetic Analysis Workshop 18 working group; these
investigators applied MLMs and data mining to analyses of rare and common genetic
variants measured in pedigrees. To develop risk profiles, group members analyzed
blood pressure traits along with single-nucleotide polymorphisms and rare variant
genotypes derived from sequence and imputation analyses in large Mexican American
pedigrees. Supervised MLMs included penalized regression with varying penalties,
support vector machines, and permanental classification. Unsupervised MLMs
included sparse principal components analysis and sparse graphical models.
Entropy-based components analyses were also used to mine these data. None of the
investigators fully capitalized on the genetic information provided by the
complete pedigrees. Their approaches either corrected for the nonindependence of
the individuals within the pedigrees or analyzed only those who were independent.
Some methods allowed for covariate adjustment, whereas others did not. We
evaluated these methods using a variety of metrics. Four contributors conducted
primary analyses on the real data, and the other two research groups used the
simulated data with and without knowledge of the underlying simulation model. One
group used the answers to the simulated data to assess power and type I errors.
Although the MLMs applied were substantially different, each research group
concluded that MLMs have advantages over standard statistical approaches with
these high-dimensional data.
PMID- 25112196
TI - Challenges of linkage analysis in the era of whole-genome sequencing.
AB - Whole-genome sequencing (WGS) is becoming an affordable technology for the study
of the genetics of complex traits. With any new technology, experimental designs
and statistical methods, both old and new, must be evaluated. One design seeing a
resurgence of interest is the use of families. Genetic Analysis Workshop 18
provided the opportunity to evaluate statistical methods applied to WGS data for
family-based studies. We summarize the results of five contributions that used
linkage in the context of WGS. The investigators took differing approaches,
including assessment of false-positive rates in classic two-point linkage, the
effects of heterogeneity on linkage and association tests, and the use of linkage
to focus association tests. We describe the primary findings of each contribution
and note challenges that are not new to those working in family designs or
specific to WGS data; for example, choice of phenotype definition, covariate
adjustment, and use of longitudinal data may produce different results, making
comparisons challenging. We detail new issues brought about by WGS, such as the
elevated genome-wide false-positive rate for classic two-point parametric linkage
analysis, computational demands in multipoint calculations, and lack of clarity
in how to best use linkage to focus association testing. Finally, we comment on
when linkage may be helpful for WGS, highlighting where additional research is
needed; for example, although linkage analysis has been successful in the study
of rare variants of large effect, how to best use family information in the
context of rare variants of moderate effect remains an open research question.
PMID- 25112195
TI - Pathway analysis approaches for rare and common variants: insights from Genetic
Analysis Workshop 18.
AB - Pathway analysis, broadly defined as a group of methods incorporating a priori
biological information from public databases, has emerged as a promising approach
for analyzing high-dimensional genomic data. As part of Genetic Analysis Workshop
18, seven research groups applied pathway analysis techniques to whole-genome
sequence data from the San Antonio Family Study. Overall, the groups found that
the potential of pathway analysis to improve detection of causal variants by
lowering the multiple-testing burden and incorporating biologic insight remains
largely unrealized. Specifically, there is a lack of best practices at each stage
of the pathway approach: annotation, analysis, interpretation, and follow-up.
Annotation of genetic variants is inconsistent across databases, incomplete, and
biased toward known genes. At the analysis stage insufficient statistical power
remains a major challenge. Analyses combining rare and common variants may have
an inflated type I error rate and may not improve detection of causal genes.
Inclusion of known causal genes may not improve statistical power, although the
fraction of explained phenotypic variance may be a more appropriate metric.
Interpretation of findings is further complicated by evidence in support of
interactions between pathways and by the lack of consensus on how to best
incorporate functional information. Finally, all presented approaches warranted
follow-up studies, both to reduce the likelihood of false-positive findings and
to identify specific causal variants within a given pathway. Despite the initial
promise of pathway analysis for modeling biological complexity of disease
phenotypes, many methodological challenges currently remain to be addressed.
PMID- 25112197
TI - Clinical behavior of Japanese community pharmacists for preventing prescription
drug overdose.
AB - AIM: Prescription drug abuse, including benzodiazepines, is a growing health
problem in Japan. This study examined the community pharmacist's clinical
behavior regarding patients who overdose on prescribed drugs, and explored the
possibility of overdose prevention by community pharmacists. METHODS: We surveyed
all registered community pharmacies with dispensing functions (n = 1867) in the
Saitama Pharmaceutical Association. An anonymous self-administered questionnaire
was mailed to each pharmacy. Respondents were asked about clinical behavior such
as medication counseling and referral to the prescriber if prescription drug
overdose was identified. RESULTS: Among respondents, 26% of community pharmacists
reported clinical experience of working with patients who overdosed on prescribed
drugs in the previous year. Half of respondents evaluated their practice such as
medication counseling and referral to the prescriber as 'good'. On multivariate
analysis, a 'poor' self-evaluation of referral to the prescriber was
significantly associated with the following perceptions: 'insufficient confidence
in communication with prescribers' (odds ratio [OR], 2.7; 95% confidence interval
[95%CI]: 1.4-5.3), and 'to avoid trouble with prescribers' (OR, 1.7; 95%CI: 1.0
2.7). CONCLUSION: Japanese community pharmacists could prevent prescription drug
abuse in their practice, but the pharmacists who have insufficient confidence in
communication with prescribers and who are afraid of trouble with a prescriber,
reported poor self-evaluation for referral to the prescribers. All prescribers
should understand the importance of referral by community pharmacists, to assist
community pharmacists in playing a critical role in prevention of prescription
drug abuse.
PMID- 25112198
TI - Analysis of tramadol and O-desmethyltramadol in decomposed skeletal tissues
following acute and repeated tramadol exposure by gas chromatography mass
spectrometry.
AB - Decomposed bone and plasma samples of rats exposed to tramadol (TRAM) under
different dosing patterns were analyzed. Wistar rats received TRAM as one acute
dose (n=4, 45 mg/kg, i.p.) or three doses (n=4, 15 mg/kg, i.p.), 40 min apart.
Perimortem heart blood was collected, rats were euthanized and placed outdoors to
decompose to skeleton. Recovered bone was ground and subjected to methanolic
extraction. Bone extracts and plasma samples underwent solid phase extraction and
were analyzed using gas chromatography-mass spectrometry. Levels of TRAM and the
primary metabolite O-desmethyltramadol (ODMT) were expressed as mass normalized
response ratios (RR/m). Levels (RR/m) for TRAM and ODMT did not differ
significantly between exposure types in any of the bone types examined or for the
pooled bone comparisons (Mann-Whitney, p>0.05). However, ratios of analyte levels
(RRTRAM/RRODMT) differed significantly between exposure patterns for tibial and
skull bone as well as for pooled bone comparisons (Mann-Whitney, p<0.05). Levels
of TRAM and ODMT, as well as ratios of analyte levels (RRTRAM/RRODMT), differed
significantly in plasma between exposure patterns. Bone TRAM and ODMT levels were
poorly correlated to corresponding plasma levels (TRAM: r=0.33-0.57; ODMT: r=
0.35-0.23).
PMID- 25112199
TI - Fluorescent dye ProteoStat to detect and discriminate intracellular amyloid-like
aggregates in Escherichia coli.
AB - The formation of amyloid aggregates is linked to the onset of an increasing
number of human disorders. Thus, there is an increasing need for methodologies
able to provide insights into protein deposition and its modulation. Many
approaches exist to study amyloids in vitro, but the techniques available for the
study of amyloid aggregation in cells are still limited and non-specific. In this
study we developed a methodology for the detection of amyloid-like aggregates
inside cells that discriminates these ordered assemblies from other intracellular
aggregates. We chose bacteria as model system, since the inclusion bodies formed
by amyloid proteins in the cytosol of bacteria resemble toxic amyloids both
structurally and functionally. Using confocal microscopy, fluorescence
spectroscopy, and flow cytometry, we show that the recently developed red
fluorescent dye ProteoStat can detect the presence of intracellular amyloid-like
deposits in living bacterial cells with high specificity, even when the target
proteins are expressed at low levels. This methodology allows quantitation of the
intracellular amyloid content, shows the potential to replace in vitro screenings
in the search for therapeutic anti-amyloidogenic compounds, and might be useful
for identifying conditions that prevent the aggregation of therapeutic
recombinant proteins.
PMID- 25112201
TI - QTL analysis of flowering time and ripening traits suggests an impact of a
genomic region on linkage group 1 in Vitis.
AB - In the recent past, genetic analyses of grapevine focused mainly on the
identification of resistance loci for major diseases such as powdery and downy
mildew. Currently, breeding programs make intensive use of these results by
applying molecular markers linked to the resistance traits. However, modern
genetics also allows to address additional agronomic traits that have
considerable impact on the selection of grapevine cultivars. In this study, we
have used linkage mapping for the identification and characterization of
flowering time and ripening traits in a mapping population from a cross of V3125
('Schiava Grossa' * 'Riesling') and the interspecific rootstock cultivar 'Borner'
(Vitis riparia * Vitis cinerea). Comparison of the flowering time QTL mapping
with data derived from a second independent segregating population identified
several common QTLs. Especially a large region on linkage group 1 proved to be of
special interest given the genetic divergence of the parents of the two
populations. The proximity of the QTL region contains two CONSTANS-like genes. In
accordance with data from other plants such as Arabidopsis thaliana and Oryza
sativa, we hypothesize that these genes are major contributors to control the
time of flowering in Vitis.
PMID- 25112200
TI - Identification and characterization of unrecognized viruses in stool samples of
non-polio acute flaccid paralysis children by simplified VIDISCA.
AB - BACKGROUND: The use of sequence independent methods combined with next generation
sequencing for identification purposes in clinical samples appears promising and
exciting results have been achieved to understand unexplained infections. One
sequence independent method, Virus Discovery based on cDNA Amplified Fragment
Length Polymorphism (VIDISCA) is capable of identifying viruses that would have
remained unidentified in standard diagnostics or cell cultures. METHODS: VIDISCA
is normally combined with next generation sequencing, however, we set up a
simplified VIDISCA which can be used in case next generation sequencing is not
possible. Stool samples of 10 patients with unexplained acute flaccid paralysis
showing cytopathic effect in rhabdomyosarcoma cells and/or mouse cells were used
to test the efficiency of this method. To further characterize the viruses,
VIDISCA-positive samples were amplified and sequenced with gene specific primers.
RESULTS: Simplified VIDISCA detected seven viruses (70%) and the proportion of
eukaryotic viral sequences from each sample ranged from 8.3 to 45.8%. Human
enterovirus EV-B97, EV-B100, echovirus-9 and echovirus-21, human parechovirus
type-3, human astrovirus probably a type-3/5 recombinant, and tetnovirus-1 were
identified. Phylogenetic analysis based on the VP1 region demonstrated that the
human enteroviruses are more divergent isolates circulating in the community.
CONCLUSION: Our data support that a simplified VIDISCA protocol can efficiently
identify unrecognized viruses grown in cell culture with low cost, limited time
without need of advanced technical expertise. Also complex data interpretation is
avoided thus the method can be used as a powerful diagnostic tool in limited
resources. Redesigning the routine diagnostics might lead to additional detection
of previously undiagnosed viruses in clinical samples of patients.
PMID- 25112202
TI - Mapping resistance to the bird cherry-oat aphid and the greenbug in wheat using
sequence-based genotyping.
AB - KEY MESSAGE: Identification of novel resistance QTL against wheat aphids. First
QTL-resistance report for R. padi in wheat and chromosome 2DL for S. graminum .
These sources have potential use in wheat breeding. The aphids Rhopalosiphum padi
and Schizaphis graminum are important pests of common wheat (Triticum aestivum
L.). Characterization of the genetic bases of resistance sources is crucial to
facilitate the development of resistant wheat cultivars to these insects. We
examined 140 recombinant inbred lines (RILs) from the cross of Seri M82 wheat
(susceptible) with the synthetic hexaploid wheat CWI76364 (resistant). RILs were
phenotyped for R. padi antibiosis and tolerance traits. Phenotyping of S.
graminum resistance was based on leaf chlorosis in a greenhouse screening and the
number of S. graminum/tiller in the field. RILs were also scored for pubescence.
Using a sequence-based genotyping method, we located genomic regions associated
with these resistance traits. A quantitative trait locus (QTL) for R. padi
antibiosis (QRp.slu.4BL) that explained 10.2 % of phenotypic variation was found
in chromosome 4BL and located 14.6 cM apart from the pubescence locus. We found
no association between plant pubescence and the resistance traits. We found two
QTLs for R. padi tolerance (QRp.slu.5AL and QRp.slu.5BL) in chromosomes 5AL and
5BL, with an epistatic interaction between a locus in chromosome 3AL
(EnQRp.slu.5AL) and QRp.slu.5AL. These genomic regions explained about 35 % of
the phenotypic variation. We re-mapped a previously reported gene for S. graminum
resistance (putatively Gba) in 7DL and found a novel QTL associated with the
number of aphids/tiller (QGb.slu-2DL) in chromosome 2DL. This is the first report
on the genetic mapping of R. padi resistance in wheat and the first report where
chromosome 2DL is shown to be associated with S. graminum resistance.
PMID- 25112203
TI - Lr70, a new gene for leaf rust resistance mapped in common wheat accession
KU3198.
AB - KEY MESSAGE: KU3198 is a common wheat accession that carries one novel leaf rust
resistance (Lr) gene, Lr70 , and another Lr gene which is either novel, Lr52 or
an allele of Lr52. Leaf rust, caused by Puccinia triticina Eriks. (Pt), is a
broadly distributed and economically important disease of wheat. Deploying
cultivars carrying effective leaf rust resistance (Lr) genes is a desirable
method of disease control. KU3198 is a common wheat (Triticum aestivum L.)
accession from the Kyoto collection that was highly resistant to Pt in Canada. An
F2 population from the cross HY644/KU3198 showed segregation for two dominant Lr
genes when tested with Pt race MBDS which was virulent on HY644. Multiple bulk
segregant analysis (MBSA) was employed to find putative chromosome locations of
these Lr genes using SSR markers that provided coverage of the genome. MBSA
predicted that the Lr genes were located on chromosomes 5B and 5D. A doubled
haploid population was generated from the cross of JBT05-714 (HY644*3/KU3198), a
line carrying one of the Lr genes from KU3198, to Thatcher. This population
segregated for a single Lr gene conferring resistance to Pt race MBDS, which was
mapped to the terminal region of the short arm of chromosome 5B with SSR markers
and given the temporary designation LrK1. One F3 family derived from the
HY644/KU3198 F2 population that segregated only for the second Lr gene from
KU3198 was identified. This family was treated as an F2-equivalent population and
used for mapping the Lr gene, which was located to the terminal region of
chromosome 5DS. As no other Lr gene has been mapped to 5DS, this gene is novel
and has been designated as Lr70.
PMID- 25112204
TI - Mapping of quantitative adult plant field resistance to leaf rust and stripe rust
in two European winter wheat populations reveals co-location of three QTL
conferring resistance to both rust pathogens.
AB - KEY MESSAGE: We detected several, most likely novel QTL for adult plant
resistance to rusts. Notably three QTL improved resistance to leaf rust and
stripe rust simultaneously indicating broad spectrum resistance QTL. The rusts of
wheat (Puccinia spp.) are destructive fungal wheat diseases. The deployment of
resistant cultivars plays a central role in integrated rust disease management.
Durability of resistance would be preferred, but is difficult to analyse. The
Austrian winter wheat cultivar Capo was released in the 1989 and grown on a large
acreage during more than two decades and maintained a good level of quantitative
leaf rust and stripe rust resistance. Two bi-parental mapping populations: Capo *
Arina and Capo * Furore were tested in multiple environments for severity of leaf
rust and stripe rust at the adult plant stage in replicated field experiments.
Quantitative trait loci associated with leaf rust and stripe rust severity were
mapped using DArT and SSR markers. Five QTL were detected in multiple
environments associated with resistance to leaf rust designated as QLr.ifa-2AL,
QLr.ifa-2BL, QLr.ifa-2BS, QLr.ifa-3BS, and QLr.ifa-5BL, and five for resistance
to stripe rust QYr.ifa-2AL, QYr.ifa-2BL, QYr.ifa-3AS, QYr.ifa-3BS, and QYr.ifa
5A. For all QTL apart from two (QYr.ifa-3AS, QLr.ifa-5BL) Capo contributed the
resistance improving allele. The leaf rust and stripe rust resistance QTL on 2AL,
2BL and 3BS mapped to the same chromosome positions, indicating either closely
linked genes or pleiotropic gene action. These three multiple disease resistance
QTL (QLr.ifa-2AL/QYr.ifa-2AL, QLr.ifa.2BL/QYr.ifa-2BL, QLr.ifa-3BS/QYr.ifa.3BS)
potentially contribute novel resistance sources for stripe rust and leaf rust.
The long-lasting resistance of Capo apparently rests upon a combination of
several genes. The described germplasm, QTL and markers are applicable for
simultaneous resistance improvement against leaf rust and stripe rust.
PMID- 25112205
TI - Mapping resistance genes for Oculimacula acuformis in Aegilops longissima.
AB - KEY MESSAGE: This study identified three QTL conferring resistance to Oculimacula
acuformis in Aegilops longissima and their associated markers, which can be
useful in marker-assisted selection breeding for eyespot resistance. Oculimacula
acuformis is one of two species of soilborne fungi that cause eyespot of wheat,
the other being Oculimacula yallundae. Both pathogens can coexist in the same
field and produce elliptical lesions on stem bases of wheat that are
indistinguishable. Pch1 and Pch2 are the only two eyespot resistance genes
readily available to wheat breeders, but neither provides complete control. A new
source of eyespot resistance was identified from Aegilops longissima (2n = 14,
S(l)S(l)), a wild relative of wheat. Three QTL for resistance to O. acuformis
were mapped in chromosomes 1S(l), 3S(l), and 5S(l) using a recombinant inbred
line population developed from the cross Ae. longissima accessions PI 542196 (R)
* PI 330486 (S). The three QTL explained 66 % of phenotypic variation by beta
glucuronidase score (GUS) and 84 % by visual rating. These QTL had LOD values of
10.6, 8.8, and 6.0 for GUS score, and 16.0, 10.0, and 13.0 for visual rating. QTL
associated with resistance to O. acuformis have similar chromosomal locations as
some for resistance to O. yallundae, except that a QTL for resistance to O.
yallundae was found in chromosome 7S(l) but not for O. acuformis. Thus, it
appears that some genes at the same locus in Ae. longissima may control
resistance to both eyespot pathogens. QTL effective against both pathogens will
be most useful for breeding programs and have potential to improve the
effectiveness and genetic diversity of eyespot resistance.
PMID- 25112207
TI - A fast way to fluorescence: a fourfold domino reaction to condensed polycyclic
compounds.
AB - A fast and efficient palladium-catalyzed fourfold domino Sonogashira/double
carbopalladation/C?H-activation reaction that converts simple aromatic systems
into complex polycyclic hydrocarbons has been developed. A number of substituted
products has thus been prepared in yields up to 89 %. The structural assignment
has been confirmed by using single-crystal X-ray crystallography. The products
show intriguing fluorescence activity and thus might serve as chemical sensors or
fluorescent imaging dyes.
PMID- 25112206
TI - The dynamic influence of emotional words on sentence processing.
AB - In the present study, we aimed to examine how the emotionality of words
influences online sentence processing-specifically, the influence of emotional
words on the processing of following words in sentences. We manipulated the
emotionality of verbs as well as the orthographic correctness of their following
(neutral) object nouns, so that the orthographic violation of the (neutral) nouns
occurred in either emotional or neutral sentences. Event-related potentials
(ERPs) were recorded to both the nouns and the verbs. We found that the
orthographic violation of the nouns elicited a P2 and an N400 effect in the
emotionally neutral sentences, but an LPC effect in the emotionally charged
sentences. We also found that the emotional verbs elicited a larger N1, a larger
P2, and a larger N400 than did the neutral verbs. The ERP results suggest that
emotional words capture more attention than neutral words, which further affects
early orthographic analysis of the following words. Our findings demonstrate a
dynamic influence of emotional words on sentence processing.
PMID- 25112208
TI - High-throughput method of dioxin analysis in aqueous samples using consecutive
solid phase extraction steps with the new C18 UltraflowTM pressurized liquid
extraction and automated clean-up.
AB - A high-throughput analytical method has been developed for the determination of
seventeen 2,3,7,8-substituted congeners of polychlorinated dibenzo-p-dioxins and
dibenzofurans (PCDD/Fs) in aqueous samples. A recently introduced octadecyl (C18)
disk for semi-automated solid-phase extraction of PCDD/Fs in water samples with a
high level of particulate material has been tested for the analysis of dioxins. A
new type of C18 disk specially designed for the analysis of hexane extractable
material (HEM), but never previously reported for use in PCDD/Fs analysis. This
kind of disk allows a higher filtration flow, and therefore the time of analysis
is reduced. The solid-phase extraction technique is used to change samples from
liquid to solid, and therefore pressurized liquid extraction (PLE) can be used in
the pre-treatment. In order to achieve efficient purification, extracts from the
PLE are purified using an automated Power-prep system with disposable silica,
alumina, and carbon columns. Quantitative analyses of PCDD/Fs were performed by
GC-HRMS using multi-ion detection (MID) mode. The method was successfully applied
to the analysis of water samples from the wastewater treatment system of a vinyl
chloride monomer plant. The entire procedure is in agreement with EPA1613
recommendations regarding the blank control, MDLs (method detection limits),
accuracy, and precision. The high-throughput method not only meets the
requirements of international standards, but also shortens the required analysis
time from 2 weeks to 3d.
PMID- 25112209
TI - Asymmetries in explosive strength following anterior cruciate ligament
reconstruction.
AB - BACKGROUND: Despite its apparent functional importance, there is a general lack
of data regarding the time-related changes in explosive strength and the
corresponding side-to-side asymmetries in individuals recovering from an ACL
reconstruction (ACLR). The present study was designed to assess changes in the
maximum and explosive strength of the quadriceps and hamstring muscles in
athletes recovering from an ACLR. METHODS: Twenty male athletes with an ACL
injury completed a standard isometric testing protocol pre-ACLR, four and
sixmonths post-ACLR. In addition to the maximum strength (Fmax), the explosive
strength of quadriceps and hamstrings was assessed through four variables derived
from the slope of the force-time curves over various time intervals (RFDmax,
RFD50, RFD150 and RFD250). Side-to-side asymmetries were calculated relative to
post-ACLR measures of the uninvolved leg ("standard" asymmetries), and relative
to pre-ACLR value of the uninvolved leg ("real" asymmetries). RESULTS: Pre-ACLR
asymmetries in quadriceps RFD (average 26%) were already larger than in Fmax
(14%) (p<0.05). Six months post-ACLR real asymmetries in RFD variables (33-39%)
were larger than the corresponding standard asymmetries (26-28%; p<0.01). Average
asymmetries in hamstrings' RFD and Fmax were 10%, 25% and 15% for pre-ACLR and
two post-ACLR sessions, respectively (all p>0.05). CONCLUSIONS: In addition to
the maximum strength, the indices of explosive strength should also be included
in monitoring recovery of muscle function following an ACLR. Furthermore, pre
injury/reconstruction values should be used for the post-ACLR side-to-side
comparisons, providing a more valid criterion regarding the muscle recovery and
readiness for a return to sports.
PMID- 25112210
TI - Synovial fluid differential cell count in wear debris synovitis after total knee
replacement.
AB - BACKGROUND: Determining the cause of synovitis following total knee arthroplasty
(TKA) can be challenging. The differential diagnoses include infection,
hemarthrosis, instability, crystalline disease, wear debris or idiopathic causes.
Wear particle synovitis can mimic periprosthetic infection with symptoms of pain
and effusion. Radiographs and physical exam are often inconclusive in
differentiating the two. Synovial fluid analysis is routinely used in evaluating
periprosthetic infections. We examined the association between synovial white
blood cell count and differentials, and polyethylene wear and osteolysis, to see
if fluid analysis can aid in establishing the diagnosis of wear particle
synovitis. METHODS: A cell count and differential was obtained from synovial
fluid samples from 54 TKAs undergoing revision for aseptic failure. Explanted
polyethylene inserts were analyzed for linear and volumetric wear, oxidation
(ketone peak height), and damage features. Analysis was performed to assess the
relationship between cell counts and polyethylene wear indicators as well as
severity of intra-operative and radiographic osteolysis. RESULTS: Total and
percent mononuclear (monocyte and lymphocyte) cell counts were found to be
elevated in the presence of documented wear debris synovitis and an association
was suggested between their levels and maximum ketone levels. CONCLUSION: The
present study implies that the differential cell count of knee fluid can help
distinguish wear debris from infection as a source of synovitis following TKA and
identifies the value of the mononuclear cell count as a possible tool to assess
abnormal wear rates of the polyethylene insert. Further research into identifying
the exact role of monocytes in the wear debris synovitis and osteolytic pathways
is warranted. LEVEL OF EVIDENCE: Level II, diagnostic study.
PMID- 25112212
TI - Histological features of the ACL remnant in partial tears.
AB - BACKGROUND: The aim of this study was to investigate the histological features of
the remaining fibers bridging the femur and tibia in partial ACL tears. METHODS:
Twenty-six ACL remnants were harvested from patients who had arthroscopic
criteria concordant with a partial tear. Histological analysis includes
cellularity, blood vessel density evaluation and characterization of the femoral
bony insertion morphology. Immunohistochemical studies were carried out to
determine cells positive for alpha-smooth actin and for mechanoreceptor
detection. RESULTS: In these samples, a normal femoral insertion of the remnant
was present in 22.7% of the cases. In 54% of the samples, substantial areas of
hypercellularity were observed. Myofibroblasts were the predominant cell type and
numerous cells positive for alpha-smooth actin were detected at immunostaining.
Blood vessel density was increased in hypercellularity areas and in the synovial
sheet. Free nerve endings and few Golgi or Ruffini corpuscles were detected in
41% of the specimens. The cellularity was correlated to the time between injury
to surgery (p=0.001). CONCLUSION: Competent histological structures including a
well-vascularized synovial sheet, numerous fibroblasts and myofibroblasts and
mechanoreceptors were found in ACL remnants. These histological findings bring
additional knowledge towards the preservation of the ACL remnant in partial tears
when ACL reconstruction or augmentation is considered. CLINICAL RELEVANCE:
Descriptive laboratory study.
PMID- 25112211
TI - Relationship of the posterior femoral axis of the "kinematically aligned" total
knee arthroplasty to the posterior condylar, transepicondylar, and
anteroposterior femoral axes.
AB - BACKGROUND: A recent proposed modification in surgical technique in total knee
arthroplasty (TKA) has been the introduction of the "kinematically aligned" TKA,
in which the angle and level of the posterior joint line of the femoral component
and joint line of the tibial component are aligned to those of the "normal," pre
arthritic knee. The purpose of this study was to establish the relationship of
the posterior femoral axis of the "kinematically aligned" total knee arthroplasty
(TKA) to the traditional axes used to set femoral component rotation. METHODS:
One hundred and fourteen consecutive, unselected patients with preoperative MRI
images undergoing TKA were retrospectively reviewed. The transepicondylar axis
(TEA), posterior condylar axis (PCA), antero-posterior axis (APA) of the
trochlear groove, and posterior femoral axis of the kinematically aligned TKA
(KAA) were templated on axial MRI images by two independent observers. The
relationships between the KAA, TEA, APA, and PCA were determined, with a negative
value indicating relative internal rotation of the axis. RESULTS: On average, the
KAA was 0.5 degrees externally rotated relative to the PCA (minimum of -3.6
degrees , maximum of 5.8 degrees ), -4.0 degrees internally rotated relative to
the TEA (minimum of -10.5 degrees , maximum of 2.3 degrees ), and -96.4 degrees
internally rotated relative to the APA (minimum of -104.5 degrees , maximum of
88.5 degrees ). Each of these relationships exhibited a wide range of potential
values. CONCLUSIONS: Using a kinematically aligned surgical technique internally
rotates the posterior femoral axis relative to the transepicondylar axis, which
significantly differs from current alignment instrument targets.
PMID- 25112213
TI - Sarcocystis arieticanis (Apicomplexa: Sarcocystidae) infecting the heart muscles
of the domestic sheep, Ovis aries (Artiodactyla: Bovidae), from K. S. A. on the
basis of light and electron microscopic data.
AB - In the present study, the heteroxenous life cycle of Sarcocystis species from
three strains of the slaughtered sheep at Al-Azizia and Al-Saada abattoirs in
Riyadh city, K.S.A., was studied. Muscle samples of the oesophagus, diaphragm,
tongue, skeletal and heart muscles were examined. Varied natural infection rates
in the muscles of the examined sheep strains were recorded as 83% in Niemy, 81.5%
in Najdy and 90% in Sawakny sheep. Muscles of the diaphragm showed the highest
infection level above all organs except Najdy sheep in which oesophagus has the
highest rate. Also, the heart was the lowest infected organ (40% Niemy, 44% Najdy
and 53% Sawakny). Microscopic sarcocysts of Sarcocystis arieticanis are easily
identified in sections through the heart muscles of the domestic sheep Ovis aries
(Artiodactyla: Bovidae). Cysts measured 38.5-64.4 MUm (averaged 42.66 MUm) in
width and 62.4-173.6 MUm (averaged 82.14 MUm) in length. The validity of this
species was confirmed by means of ultrastructural characteristics of the primary
cyst wall (0.1-0.27 MUm thick) which revealed the presence of irregularly shaped
crowded and hairy-like projections underlined by a thin layer of ground
substance. This layer consisted mainly of fine, dense homogenous granules
enclosing the developing metrocytes and merozoites that usually contain nearly
all the structures of the apical complex and fill the interior cavity of the
cyst. Several septa derived from the ground substance divided the cyst into
compartments. The merozoites were banana-shaped and measured 12-16 MUm in length
with centrally or posteriorly located nuclei. Experimental infection of
carnivores by feeding heavily infected sheep muscles revealed that the dog, Canis
familiaris, is the only final host of the present Sarcocystis species. Gamogony,
sporogonic stages and characteristics of sporulated oocysts were also
investigated.
PMID- 25112214
TI - Clamp ultrastructure of the basal monogenean Chimaericola leptogaster (Leuckart,
1830) (Polyopisthocotylea: Chimaericolidae).
AB - The ultrastructure of the haptoral clamps of the chimaericolid monogenean
Chimaericola leptogaster, a basal polyopisthocotylean from the gills of a
holocephalan fish, is described. These clamps are characterized by the presence
of two muscle blocks interrupted mid-anteriorly and mid-posteriorly and different
kinds of hard structures: a single median and paired lateral sclerites embedded
in the clamp wall; six spine-like structures directed towards the clamp lumen;
and electron dense surface structures along the internal surface of the anterior
clamp lips and along the luminal surface of the tegument of the clamp lumen. The
lateral sclerites are situated deep within muscular tissue and are closely
bounded by radial myofibrils, possessing a uniform electron dense matrix within
which are hollow areas of different sizes. The median sclerite occupies an area
between the clamp wall myofibrils and the luminal epithelium, is surrounded by a
basement lamina and is composed of a heterogeneous matrix comprising two
different morphological layers related to variations in the type and
concentration of fibrils. Four of the spine-like structures are extensions of the
margins of the two spindle-like muscle blocks in the clamps, i.e. the two
anterior and two posterior structures, and the two others are situated at the
lateral constrictions of the left and right muscle blocks. The electron dense
surface structures are derivations of the clamp tegument or, to be more precise,
its outer, densely fibrous region. These results are discussed in relation to the
evidence that the haptoral clamps of C. leptogaster are apparently ancient
origin.
PMID- 25112215
TI - The role of quorum sensing system in antimicrobial induced ampC expression in
Pseudomonas aeruginosa biofilm.
AB - The aim of this study was to evaluate the effects of quorum sensing (QS) systems
in Pseudomonas aeruginosa (P. aeruginosa) on the expression of ampC gene induced
by antibiotics. An in vitro dynamic model of P. aeruginosa biofilms was
established in a silicon tube in once-flowthrough system at 37 degrees C.
Biofilm generation was identified by argentation. Biofilm morphology of standard
P. aeruginosa strain (PAO-1) and QS systems deficient strains (PDO100, rhlI
deficient strain; PAO-JP1, lasI deficient strain; and PAO-MW1, rhlI and lasI
deficient strain) were observed by optical microscope. The expression of ampC in
PAO1, PAO1 with QS inhibitor (furanone C-30) and the QS deficient strains before
and after induced by antibiotics were quantified by real-time quantitative PCR.
The biofilms of PAO-1 and PDO100 were much thicker and denser than that of PAO
JP1 and PAO-MW1. Being induced by antibiotics, the expression of ampC in PAO1 and
PDO100 was significantly higher than that in PAO-MW1 and PAO-JP1. With the effect
of furanone C-30, the expression of ampC in PAO1 induced by antibiotics was
reduced in a dose-dependent manner. QS system, especially the las system, plays
an important role in both biofilm formation and antimicrobials induced ampC
expression and furanone C-30 is a potent inhibitor for P. aeruginosa QS system.
PMID- 25112216
TI - Cell penetration: scope and limitations by the application of cell-penetrating
peptides.
AB - The penetration of polar or badly soluble compounds through a cell membrane into
live cells requires mechanical support or chemical helpers. Cell-penetrating
peptides (CPPs) are very promising chemical helpers. Because of their low
cytotoxicity and final degradation to amino acids, they are particularly favored
in in vivo studies and for clinical applications. Clearly, the future of CPP
research is bright; however, the required optimization studies for each drug
require considerable individualized attention. Thus, CPPs are not the
philosopher's stone. As of today, a large number of such transporter peptides
with very different sequences have been identified. These have different uptake
mechanisms and can transport different cargos. Intracellular concentrations of
cargos can reach a low micromole range and are able to influence intracellular
reactions. Internalized ribonucleic acids such as small interfering RNA (siRNA)
and mimics of RNA such as peptide nucleic acids, morpholino nucleic acids, and
triesters of oligonucleotides can influence transcription and translation.
Despite the highly efficient internalization of antibodies, enzymes, and other
protein factors, as well as siRNA and RNA mimics, the uptake and stabile
insertion of DNA into the genome of the host cells remain substantially
challenging. This review describes a wide array of differing CPPs, cargos, cell
lines, and tissues. The application of CPPs is compared with electroporation,
magnetofection, lipofection, viral vectors, dendrimers, and nanoparticles,
including commercially available products. The limitations of CPPs include low
cell and tissue selectivity of the first generation and the necessity for
formation of fusion proteins, conjugates, or noncovalent complexes to different
cargos and of cargo release from intracellular vesicles. Furthermore, the
noncovalent complexes require a strong molar excess of CPPs, and extensive
experimentation is required to determine the most optimal CPP for any given cargo
and cell type. Yet to predict which CPP is optimal for any given target remains a
complex question. More recently, there have been promising developments: the
enhancement of cell specificity using activatable CPPs, specific transport into
cell organelles by insertion of corresponding localization sequences, and the
transport of drugs through blood-brain barriers, through the conjunctiva of eyes,
skin, and into nerve cells. Proteins, siRNA, and mimics of oligonucleotides can
be efficiently transported into cells and have been tested for treatment of
certain diseases. The recent state of the art in CPP research is discussed
together with the overall scope, limitations, and some recommendations for future
research directions.
PMID- 25112217
TI - Comorbid Problem Gambling and Major Depression in a Community Sample.
AB - Major depression is among the most common comorbid conditions in problem
gambling. However, little is known about the effects of comorbid depression on
problem gambling. The present study examined the prevalence of current major
depression among problem gamblers (N = 105) identified from a community sample of
men and women in Alberta, and examined group differences in gambling severity,
escape motivation for gambling, family functioning, childhood trauma, and
personality traits across problem gamblers with and without comorbid depression.
The prevalence of major depression among the sample of problem gamblers was
32.4%. Compared to problem gamblers without depression (n = 71), problem gamblers
with comorbid depression (n = 34) reported more severe gambling problems, greater
history of childhood abuse and neglect, poorer family functioning, higher levels
of neuroticism, and lower levels of extraversion, agreeableness, and
conscientiousness. Furthermore, the problem gamblers with comorbid depression had
greater levels of childhood abuse and neglect, worse family functioning, higher
neuroticism, and lower agreeableness and conscientiousness than a comparison
sample of recreational gamblers with depression (n = 160). These findings
underscore the need to address comorbid depression in assessment and treatment of
problem gambling and for continued research on how problem gambling is related to
frequently co-occurring disorders such as depression.
PMID- 25112219
TI - Gender Differences in Risk Aversion Among Chinese University Students.
AB - This paper examines gender differences in risk aversion among Chinese university
students. Chinese females are proposed to be more risk averse and require a
higher risk premium when faced with a gamble option in the gain-domain frame as
compared to Chinese males. Two groups of 100 participants each (male = 100 and
female = 100 in total) were recruited to fill up questionnaires that included
items relating to objective probability lotteries. Within each group, it was
found that Chinese males and females did not differ in their risk aversion.
However, results show that Chinese males tend to react more readily to rising
risk premium by taking up options with higher expected values when compared to
Chinese females. Current findings will have useful implications to marketers
(particularly, promoters of gambling products) and problem gambling counselors.
PMID- 25112218
TI - The Relationship Between Gambling and Homelessness: A Commentary on Sharman et
al. (2014).
AB - The relationship between problem gambling and homelessness is a little studied
area in the gambling studies field. A recent study by Sharman et al. (J Gambl
Stud, doi: 10.1007/s10899-014-9444-7, 2014) is the first quantitative study in
Great Britain on this interesting and important topic. In this context, the study
is to be commended and provides an empirical benchmark on which other studies can
build. The study reported a problem gambling prevalence rate of 11.6% and is
significantly higher than the problem gambling rate of the general population in
Great Britain (which is <1%). However, given the political sensitivity
surrounding the expansion of bookmakers in the UK, the study needs further
contextualization otherwise the findings of such studies may be used by anti
gambling lobby groups to serve their own political agendas. While it is good that
such an area has been empirically investigated in Great Britain, this paper
briefly (1) places the issue of problem gambling among the homeless into the
wider context of problems among the homeless more generally (particularly in
relation to mental health problems and other addictive behaviors), (2) highlights
some of the methodological problems and weaknesses of the study, and (3) notes a
number of factual errors made in the paper.
PMID- 25112220
TI - A Resource Model of Change: Client Factors that Influence Problem Gambling
Treatment Outcomes.
AB - This study examined a resource-based model of change whereby poor problem
gambling (PG) treatment outcomes and relapse are viewed as resulting from client
coping resources being diminished or overwhelmed. Specifically, client factors
that work like resources to facilitate treatment (i.e., social support, self
efficacy, motivation, readiness for change, and emotion-focused coping) or use up
resources and hinder treatment (i.e., co-morbid depression and life stress) were
examined. The 50 participants were followed for 4 months after entering treatment
for PG and were assessed at baseline, 1 month into treatment, 2 months into
treatment, and during a follow-up 4 months after treatment began. Of the 50
participants, 20 dropped-out of treatment and 24 completed the follow-up measure.
The results suggest that self-efficacy and depression, measured at baseline, are
good predictors of 1- and 2-month outcomes, whereas depression and life stress,
measured after 2 months of treatment, are good predictors of 4-month outcomes. In
the strongest of these models, baseline scores of client self-efficacy and
depressed affect explained as much as 48.7% of the variance in gambling behaviors
2 months later.
PMID- 25112222
TI - Impulse control disorders are associated with multiple psychiatric symptoms in
Parkinson's disease.
AB - BACKGROUND: Impulse control disorders can have serious adverse consequences to
the life of a patient with Parkinson's disease. Although impulse control
disorders are common, a possible psychiatric comorbidity has not been fully
characterized. OBJECTIVE: The aim of this study was to investigate the
psychiatric symptoms exhibited by Parkinson's disease patients with impulse
control disorders. METHODS: The study was conducted as a postal survey to
patients in the registry of the Finnish Parkinson Association. A total of 290
Parkinson's disease patients were evaluated for impulse control disorders using
the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease.
Psychiatric symptoms were systematically screened using the Symptom Checklist 90.
RESULTS: We found that 108 of the evaluated patients had one or more impulse
control disorders. Patients with impulse control disorders had markedly higher
scores for symptoms of psychoticism (Bonferroni corrected p < 0.001),
interpersonal sensitivity (p < 0.001), obsessive-compulsive disorder (p < 0.001),
and depression (p = 0.01) when compared with patients without impulse control
disorders. Impulse control disorders were shown to be independently associated
with these symptoms. Patients with multiple impulse control disorders had higher
scores for depression and obsessive-compulsive symptoms when compared with
patients that exhibited only one impulse control disorder. COUNCLUSIONS: Our
results confirm the previous observations that impulse control disorders in
Parkinson's disease are linked with multiple psychiatric symptoms, including
psychoticism, interpersonal sensitivity, obsessive-compulsive symptoms and
depression. Clinicians treating these patients should acknowledge the concomitant
psychiatric symptoms.
PMID- 25112223
TI - Measuring stem cell dynamics in the human colon--where there's a wiggle, there's
a way.
AB - The last decade has seen huge improvements in our understanding of intestinal
stem cell biology, with major advances arising from the ability to transgenically
label, and thus identify, murine stem cells and their progeny. In the human,
transgenic labelling is not an available option and stem cell dynamic
observations have been based on rare hereditary mutations and polymorphisms.
Somatic mitochondrial DNA mutations cause a histochemically detectable, but
neutrally selected, change in cytochrome c oxidase (CCO) enzyme activity and when
this occurs in an intestinal stem cell, it can be used as an effective clonal
marker in both health and disease. The intestinal crypt is the functional unit of
the gut. Daughter cells are 'born' in the stem cell niche at the crypt base and
proliferate, differentiate, and then apoptose as they migrate along the vertical
crypt axis over 5-7 days. This stereotypical architecture provides a historical
record of cell dynamics, as the distance travelled along the crypt axis is
proportional to the time since the daughter cell was born. By staining,
identifying, and carefully reconstructing crypt maps from serial en face sections
of partially mutated mtDNA crypts, clonal ribbon images can be generated.
'Wiggles' in the width of the clonal ribbon reflect mtDNA mutated stem cell
expansion or contraction events and these biological observations are applied in
mathematical models. This clever approach is able to infer temporal evolutionary
dynamics from a static, single time point measurement, in both normal and
familial adenomatous polyposis tissue. As we have seen in the mouse, the simple
ability to identify stem cell progeny can lead to a vast expansion in our
understanding of stem cell evolution. The use of these techniques to trace recent
stem cell dynamics in the human colon makes some headway into the knowledge gap
in our understanding of murine and human intestinal stem cell biology. (c) 2014
The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on
behalf of Pathological Society of Great Britain and Ireland.
PMID- 25112224
TI - [Clearer labelling is required on tubes emitting ultraviolet C to prevent skin
and eye lesions].
PMID- 25112225
TI - Detoxification of furfural in Corynebacterium glutamicum under aerobic and
anaerobic conditions.
AB - The toxic fermentation inhibitors in lignocellulosic hydrolysates raise serious
problems for the microbial production of fuels and chemicals. Furfural is
considered to be one of the most toxic compounds among these inhibitors. Here, we
describe the detoxification of furfural in Corynebacterium glutamicum ATCC13032
under both aerobic and anaerobic conditions. Under aerobic culture conditions,
furfuryl alcohol and 2-furoic acid were produced as detoxification products of
furfural. The ratio of the products varied depending on the initial furfural
concentration. Neither furfuryl alcohol nor 2-furoic acid showed any toxic effect
on cell growth, and both compounds were determined to be the end products of
furfural degradation. Interestingly, unlike under aerobic conditions, most of the
furfural was converted to furfuryl alcohol under anaerobic conditions, without
affecting the glucose consumption rate. Both the NADH/NAD(+) and NADPH/NADP(+)
ratio decreased in the accordance with furfural concentration under both aerobic
and anaerobic conditions. These results indicate the presence of a single or
multiple endogenous enzymes with broad and high affinity for furfural and co
factors in C. glutamicum ATCC13032.
PMID- 25112226
TI - Engineering color variants of green fluorescent protein (GFP) for
thermostability, pH-sensitivity, and improved folding kinetics.
AB - A number of studies have been conducted to improve chromophore maturation,
folding kinetics, thermostability, and other traits of green fluorescent protein
(GFP). However, no specific work aimed at improving the thermostability of the
yellow fluorescent protein (YFP) and of the pH-sensitive, yet thermostable color
variants of GFP has so far been done. The protein variants reported in this study
were improved through rational multiple site-directed mutagenesis of GFP (ASV) by
introducing up to ten point mutations including the mutations near and at the
chromophore region. Therefore, we report the development and characterization of
fast folder and thermo-tolerant green variant (FF-GFP), and a fast folder
thermostable yellow fluorescent protein (FFTS-YFP) endowed with remarkably
improved thermostability and folding kinetics. We demonstrate that the
fluorescence intensity of this yellow variant is not affected by heating at 75
degrees C. Moreover, we have developed a pH-unresponsive cyan variant AcS-CFP,
which has potential use as part of in vivo imaging irrespective of intracellular
pH. The combined improved properties make these fluorescent variants ideal tools
to study protein expression and function under different pH environments, in
mesophiles and thermophiles. Furthermore, coupling of the FFTS-YFP and AcS-CFP
could potentially serve as an ideal tool to perform functional analysis of live
cells by multicolor labeling.
PMID- 25112227
TI - Surgical treatment of prolactinomas: cons.
AB - Prolactinomas account for approximately 40 % of all pituitary adenomas. Over 95 %
of prolactinomas are microadenomas (< 10 mm diameter). Treatment is indicated to
correct hypogonadism, restore other hormonal deficits, and alleviate local mass
effects. Dopamine agonists (DA) are highly effective in achieving these goals and
are well-tolerated. The vast majority of prolactinomas will respond to
conventional doses of cabergoline (<=2 mg/week) that do not carry an increased
risk of cardiac valvular abnormalities. DA therapy may be successful withdrawn in
a subset of patients and thus is not necessarily a lifelong commitment. Although
transsphenoidal surgery (TSS) is an option for prolactinoma treatment, it is less
effective than medical management, carries considerably more risk, and is more
expensive. The benefit/risk ratio for DA therapy compared to TSS actually becomes
increasingly more favorable as tumor size increases. Therefore DA should remain
the clear treatment of choice for essentially all patients with prolactinomas,
reserving TSS as a second-line option for the very small number of patients that
do not tolerate or are completely resistant to DA therapy.
PMID- 25112228
TI - Treatment of hyperprolactinemia in post-menopausal women: pros.
AB - The incidence of hyperprolactinemia in women peaks during the 3rd-4th decade and
then greatly decreases after the menopause. Apart from the effects on the
hypothalamic-pituitary-gonadal axis, prolactin can act directly on bone
metabolism. Hyperprolactinemia is a recognized cause of secondary osteoporosis,
and treatment with dopamine agonists can lead to improved BMD. Moreover,
hyperprolactinemia has been linked to weight gain and insulin resistance, which
can be ameliorated following medical treatment. Although relatively rare,
prolactinomas can be observed in post-menopausal women and are frequently large
and invasive; dopamine agonists appear to be as effective in these patients as in
younger women to induce reduction of prolactin levels and tumour shrinkage. Here,
we review data potentially favouring medical treatment with dopamine agonists in
post-menopausal women diagnosed with hyperprolactinemia.
PMID- 25112229
TI - Interventions to reduce inappropriate prescribing of antipsychotic medications in
people with dementia resident in care homes: a systematic review.
AB - BACKGROUND: Antipsychotic medications are commonly used to manage the behavioral
and psychological symptoms of dementia. Several large studies have demonstrated
an association between treatment with antipsychotics and increased morbidity and
mortality in people with dementia. AIMS: To assess the effectiveness of
interventions used to reduce inappropriate prescribing of antipsychotics to the
elderly with dementia in residential care. METHOD: Systematic searches were
conducted in 12 electronic databases. Reference lists of all included studies and
forward citation searching using Web of Science were also conducted. All
quantitative studies with a comparative research design and studies in which
recognized methods of qualitative data collection were used were included.
Articles were screened for inclusion independently by 2 reviewers. Data
extraction and quality appraisal were performed by 1 reviewer and checked by a
second with discrepancies resolved by discussion with a third if necessary.
RESULTS: Twenty-two quantitative studies (reported in 23 articles) were included
evaluating the effectiveness of educational programs (n = 11), in-reach services
(n = 2), medication review (n = 4), and multicomponent interventions (n = 5). No
qualitative studies meeting our inclusion criteria were identified. Eleven
studies were randomized or controlled in design; the remainder were uncontrolled
before and after studies. Beneficial effects were seen in 9 of the 11 studies
with the most robust study design with reductions in antipsychotic prescribing
levels of between 12% and 20%. Little empirical information was provided on the
sustainability of interventions. CONCLUSION: Interventions to reduce
inappropriate prescribing of antipsychotic medications to people with dementia
resident in care homes may be effective in the short term, but longer more robust
studies are needed. For prescribing levels to be reduced in the long term, the
culture and nature of care settings and the availability and feasibility of
nondrug alternatives needs to be addressed.
PMID- 25112230
TI - Low serum selenium level is associated with low muscle mass in the community
dwelling elderly.
AB - OBJECTIVES: Elderly persons with low muscle mass (LMM) or sarcopenia are prone to
frailty and functional decline. This study aimed to investigate the relationship
between serum selenium level and skeletal muscle mass in community-dwelling
elderly. DESIGN: Cross-sectional observational study. SETTING AND PARTICIPANTS: A
total of 327 elderly Taipei citizens (mean age 71.5 +/- 4.7 years) were recruited
from the community. MEASUREMENTS: Skeletal muscle mass was measured by
bioelectrical impedance analysis. LMM was defined by low skeletal muscle index
(SMI: muscle mass (kg)/[height (m)](2)). All participants were further divided
into quartiles by serum selenium level and the risk for LMM among these quartiles
was examined using multivariate logistic regression analyses. Estimated serum
selenium levels for the LMM group vs the normal group and estimated SMI in the
quartiles of serum selenium were computed by least square method in linear
regression models. RESULTS: The estimated mean (+/-standard deviation) of serum
selenium level was significantly lower in the LMM group compared with the normal
group after adjusting for confounders (1.01 +/- 0.03 MUmol/L vs 1.14 +/- 0.02
MUmol/L, P < .001). After adjusting for age, sex, lifestyle, and physical and
metabolic factors, the odds ratios (95% confidence interval, P value) of LMM in
the bottom, second, and third selenium quartile groups were 4.62 (95% CI 2.11
10.10, P < .001), 2.30 (95% CI 1.05-5.03, P < .05) and 1.51 (95% CI 0.66-3.46, P
= .327), respectively, compared with the top quartile group of serum selenium
level. The least square mean of SMI increased with the quartiles of serum
selenium (P < .001). CONCLUSIONS: This is the first study to demonstrate that low
serum selenium is independently associated with low muscle mass in the elderly.
The causality and underlying mechanism between selenium and low muscle mass or
sarcopenia warrant further research.
PMID- 25112231
TI - Obesity: cerebral damage in obesity-associated metabolic syndrome.
AB - The prevalence of the metabolic syndrome has increased in tandem with that of
obesity. The metabolic syndrome is associated with structural and functional
cerebral damage. A new study confirms the association between the metabolic
syndrome and reduced brain volume in the absence of diabetes mellitus. Here, we
highlight how vascular dysfunction potentially contributes to this brain damage.
PMID- 25112232
TI - Biomarkers: Sclerostin levels linked to CKD outcomes.
PMID- 25112233
TI - Diabetes: Protective role of autophagy in pancreatic beta cells.
PMID- 25112234
TI - Diabetes: insulin pump therapy for type 2 diabetes mellitus.
AB - The evidence base for the efficacy of insulin pump therapy in type 2 diabetes
mellitus (T2DM) has been inconsistent to date. However, a recent large-scale
randomized controlled trial comparing pump treatment with multiple daily insulin
injections in patients with poorly controlled T2DM has shown substantial
improvement in glycaemic control with pump therapy.
PMID- 25112236
TI - Streaming potential and electroviscous effects in soft nanochannels: towards
designing more efficient nanofluidic electrochemomechanical energy converters.
AB - In this paper we provide analytical solutions for the streaming potential and
electroviscous effects in soft nanochannels. The analysis is based on the
solution of the linearized Poisson-Boltzmann equation, valid for small
electrostatic potentials. We identify the important dimensionless parameters that
dictate these two effects. Results are provided for a large range of electric
double layer (EDL) thickness values, spanning from the case of very thin to very
large overlapped EDL thicknesses. We compare the results with those of a rigid
nanochannel, having zeta potential equal to the electrostatic potential at the
solid-polyelectrolyte interface of the soft nanochannels. For the soft
nanochannel, the streaming potential varies very weakly with the EDL thickness
and can be substantially larger than that corresponding to the rigid nanochannel.
The electroviscous effects for the soft nanochannel, unlike the rigid
nanochannel, virtually always exhibit a monotonic decrease with the EDL
thickness, and for certain parameter ranges can be several times larger than that
for a rigid nanochannel. Most importantly, for the soft nanochannels the
electrochemomechanical energy conversion, associated with the generation of
streaming potential, is found to be highly efficient, with the efficiency being
several times higher than that of a rigid nanochannel.
PMID- 25112237
TI - Australian marsh beetles (Coleoptera: Scirtidae). 6. Genera Calvarium Pic,
Papuacyphon Zwick, and Ypsiloncyphon Klausnitzer.
AB - The genus Calvarium Pic, 1918 is for the first time recorded from Australia. Six
new Australian species are named and described. Calvarium australiense n. sp. and
C. superbum n. sp. from the Northern Territory are typical representatives of the
genus. A new subgenus, Calvariellum n. subgen., is proposed for four species from
NE Queensland which share general body structure with other Calvarium species but
have different, less derived male genitalia: Calvarium (Calvariellum)
bellendenker n. sp., C. (Calvariellum) cochlearifer n. sp., C. (Calvariellum)
hamifer n. sp., and C. (Calvariellum) lancifer n. sp. Papuacyphon darwini n. sp.
is described from SW Australia. The genus was previously known only from Papua
New Guinea. Species Group 3 of the genus Ypsiloncyphon Klausnitzer, 2009 is first
recorded from Australia. It is endemic to the Australasian region. The Australian
species Y. angustus n. sp., Y. brevis n. sp., Y. katherinae n. sp., Y. longus n.
sp., Y. pusillus n. sp., Y. velatus n. sp., and Y. virgulifer n. sp. are
described, the New Guinean species Y. micans (Klausnitzer, 1973) (= Cyphon
paramicans Klausnitzer, 1973, n. syn.), Y. mutilatus n. sp., Y. ruficollis n.
sp., and Y. rugosus n. sp. are described or redescribed from types, respectively.
Three Australian species known only in the female sex are described under
informal designations.
PMID- 25112238
TI - Synopsis of Oryssomini Gordon (Coleoptera: Coccinellidae) from the Neotropical
region with new species of Oryssomus Mulsant, Pseudoryssomus Gordon and
Gordonoryssomus Almeida & Lima.
AB - Six new species of Oryssomus are described: O. calix sp. nov., O. guillermo sp.
nov., O. guyanensis sp. nov. and O. rhombus sp. nov., from French Guiana; and O.
paschoali sp. nov. and O. rogeri sp. nov., from Brazil. Four new species of
Pseudoryssomus are described: P. brulei sp. nov., P. crucifer sp. nov., P.
triangulus sp. nov., from French Guiana; and P. rufomarginatus sp. nov., from
Trinidad and Tobago. Three new species of Gordonoryssomus are described: G.
mirnae sp. nov., from Peru, G. everardoi sp. nov. and G. limeirai sp. nov., from
Brazil. The new species are placed within the South American classification of
Gordon (1974) and Almeida & Lima (1995). Keys to genera and species of Oryssomus,
Pseudoryssomus and Gordonoryssomus are included. Distribution maps and a
checklist of the known species of Oryssomini are provided.
PMID- 25112239
TI - An annotated checklist of scale insects (Hemiptera: Coccoidea) of Saint Lucia,
Lesser Antilles .
AB - An annotated list of 83 scale insect species (Hemiptera: Sterorrhyncha:
Coccoidea) recorded from Saint Lucia is presented, based on data gathered from UK
quarantine interceptions, samples collected in an urban coastal habitat in the
North West of the Island in 2013, and published records. Thirty-three species
(40%) are recorded for the first time for the country, including Dysmicoccus
joannesiae (Costa Lima), a South American mealybug, and Poliaspoides formosana
(Takahashi), an Asian armoured scale insect pest of bamboo, which are new for the
Caribbean region. The economic, environmental and social impacts caused by
introduced exotic species of scale insect are discussed. Two predatory midges
Diadiplosis ?coccidivora (Felt) and Diadiplosis multifila (Felt) (Diptera:
Cecidomyiidae) are recorded for the first time from Saint Lucia. The latter
species was observed causing 90% mortality of a large infestation of passion vine
mealybug Planococcus minor (Maskell) on soursop fruit.
PMID- 25112235
TI - Gynaecomastia--pathophysiology, diagnosis and treatment.
AB - Gynaecomastia (enlargement of the male breast tissue) is a common finding in the
general population. Most cases of gynaecomastia are benign and of cosmetic,
rather than clinical, importance. However, the condition might cause local pain
and tenderness, could occasionally be the result of a serious underlying illness
or a medication, or be inherited. Breast cancer in men is much less common than
benign gynaecomastia, and the two conditions can usually be distinguished by a
careful physical examination. Estrogens are known to stimulate the growth of
breast tissue, whereas androgens inhibit it; most cases of gynaecomastia result
from deficient androgen action or excessive estrogen action in the breast tissue.
In some cases, such as pubertal gynaecomastia, the breast enlargement resolves
spontaneously. In other situations, more active treatment might be required to
correct an underlying condition (such as hyperthyroidism or a benign Leydig cell
tumour of the testis) or medications that could cause breast enlargement (such as
spironolactone) might need to be discontinued. For men with hypogonadism,
administration of androgens might be helpful, as might antiestrogen therapy in
men with endogenous overproduction of estrogens. Surgery to remove the enlarged
breast tissue might be necessary when gynaecomastia does not resolve
spontaneously or with medical therapy.
PMID- 25112241
TI - Cleridae (Insecta: Coleoptera) type collection at National Forest Insect
Collection (NFIC), Forest Research Institute, Dehradun (India).
AB - Clerids are small predacious beetles (Coleoptera) that belong to the family
Cleridae. In the National Forest Insect Collection (NFIC) Cleridae is represented
by 31 authentically identified specimens including types of 27 species. The type
material of Cleridae, deposited in the NFIC, Forest Research Institute, Dehradun
(India), is listed and illustrated with digital automontage photographs. A list
of 27 type species of Cleridae, 13 holotypes and 14 paratypes with information on
species names, reference of the original publication, all available information
on labels of types (country, locality, date of collection, collector name, etc)
along with colored photographs of types and the labels that are attached to them,
taken with Auto-montage 3-D imaging system, is provided.
PMID- 25112240
TI - Two new genera and five new species of Teloganodidae (Ephemeroptera) from South
India.
AB - Two new genera and five new species of teloganodid mayflies (Ephemeroptera:
Pannota: Ephemerelloidea) are described based on larvae from south India:
Janohyphella indica, n. gen., n. sp., Indoganodes jobini, n. gen., n. sp.,
Teloganodes sartorii, n. sp., Dudgeodes palnius, n. sp., and Derlethina
tamiraparaniae, n. sp. Janohyphella, n. gen., is distinguished from the larvae
of other teloganodid genera by having a combination of three subequal caudal
filaments, lamellate gills on abdominal segments II through V and posterolateral
processes well-developed on abdominal segments II through IX, except III.
Indoganodes, n. gen., is distinguished from the larvae of other teloganodid
genera by having three subequal caudal filaments, lamellate gills on abdominal
segments II through VI, posterolateral projections weakly developed on abdominal
segments I through V, but distinct on segments VI through IX. Our new species of
Dudgeodes Sartori, 2008 and Derlethina Sartori, 2008 represent the first
discoveries of these genera outside Southeast Asia, with the latter genus
previously considered endemic to Borneo. Emendations to the larval species key of
known Oriental Teloganodidae are provided. We hypothesize that the occurrence of
the new taxa in southern India is a result of the tectonic events associated with
the split-up of Gondwana. This illustrates the profound biogeographical
significance of how vicariance led to the establishment of some distinct oriental
lineages initially on the rafting Indian Deccan Plate, which might have triggered
dispersal events for subsequent species diversification in Southeast Asia.
PMID- 25112242
TI - A new species of Hetereleotris (Perciformes: Gobiidae) from Farasan Island (Red
Sea).
AB - A new species of the genus Hetereleotris is described from Farasan Island, Saudi
Arabia, Red Sea, on the basis of a single specimen. Hetereleotris dorsovittata
sp. nov is unique among the known sixteen species of Hetereleotris, except for H.
diademata and H. psammophila, in the combination of the absence of head canals
and lack of squamation. The low count of pectoral-fin rays (14) is only overlap
with H. psammophila (14 or 15), whereas all other Hetereleotris species have a
higher number of pectoral-fin rays. The new species differs from H. psammophila
in having more soft rays in the dorsal and anal fins, by the arrangement of
papillae in the preoperculo-mandibular row i and by coloration. The single
specimen was collected in the large lagoon at the base of an isolated small coral
patch at a depth of 1m.
PMID- 25112243
TI - New data on the genus Micromus Rambur, 1842 from China (Neuroptera,
Hemerobiidae), with a key to Chinese species.
AB - A review of the genus Micromus Rambur from China is presented. A new species,
Micromus setulosus sp. nov., which was found in Ningxia province, is described.
The male of Micromus pallidius (Yang, 1987) and the female of Micromus perelegans
Tjeder, 1936 are described for the first time in China. Keys to the adult males
and females of the Micromus from China are also given.
PMID- 25112244
TI - Rumen ciliates in the African (Cape) buffalo (Syncerus caffer caffer) living in
the vicinity of the Orpen Gate entrance into Kruger National Park, South Africa.
AB - Samples of rumen contents were obtained from 10 African (Cape) buffalo living in
the vicinity of the Orpen Gate entrance into Kruger National Park in South
Africa. Total number of ciliate protozoa per animal ranged from 3.15 to 23.25 x
103. Forty three different species and forms were observed, of which
35 are a new host record. The total number of species and forms per animal varied
from 10 to 17. Eudiplodinium maggii occurred in all 10 animals, followed by
Dasytricha ruminantium in nine animals. Diplodinium posterovesiculatum,
Eudiplodinium magnodentatum and Ostracodinium mammosum were present in seven
animals with all other species and forms occurring in five or less animals.
PMID- 25112245
TI - The first species of the spider genus Episinus in Colombia (Araneae,
Theridiidae).
PMID- 25112246
TI - Revision of the systematics of the cardinalfishes (Percomorpha: Apogonidae) based
on molecular analyses and comparative reevaluation of morphological characters.
AB - Molecular analyses were conducted based on 120 of the estimated 358 species of
the family Apogonidae with 33 of 40 genera and subgenera, using three gobioids
and one kurtid as collective outgroups. Species of Amioides, Apogon,
Apogonichthyoides, Apogonichthys, Archamia, Astrapogon, Brephamia, Cercamia,
Cheilodipterus, Fibramia n. gen., Foa, Fowleria, Glossamia, Gymnapogon, Jaydia,
Lachneratus, Nectamia, Ostorhinchus, Paroncheilus, Phaeoptyx, Pristiapogon,
Pristicon, Pseudamia, Pterapogon, Rhabdamia, Siphamia, Sphaeramia, Taeniamia,
Verulux, Vincentia, Yarica, Zapogon and Zoramia were present in the molecular
analyses; species of Bentuviaichthys, Holapogon, Lepidamia, Neamia, Paxton,
Pseudamiops and Quinca were absent from the analyses. Maximum-likelihood (ML),
Bayesian (BA), and Maximum parsimony (MP) analyses based on two mitochondrial
(12S rRNA-tRNAVal-16S rRNA, ca. 1500 bp; COI, ca. 1500 bp) and two nuclear DNA
(RAG1, ca. 1300 bp; ENC1, ca. 800 bp) fragments reproduced two basal clades
within the monophyletic family: one including a single species, Amioides
polyacanthus, and the other comprising species of Pseudamia. All the other
apogonid species formed a large well-established monophyletic group, in which
almost identical 12 major clades were reproduced, with phylogenetic positions of
four species (Glossamia aprion, Ostorhinchus margaritophorus, Pterapogon
kauderni, and Vincentia novaehollandiae) left unsettled. Apogon sensu lato and
recent Ostorhinchus (excepting O. margaritophorus) were divided into six and
three major clades, respectively. Each of the recognized clades in the family was
then evaluated for morphological characters to identify synapomorphies. Based on
the results of the molecular analyses and the reevaluation of morphological
characters, four subfamilies were proposed within the family: Apogoninae
(including most of the species in the family), Amioidinae new subfamily
(including Amioides, and based on morphology, Holapogon), Paxtoninae new
subfamily (including Paxton, based only on morphology) and Pseudamiinae
(including Pseudamia). Within the largest subfamily Apogoninae, twelve new tribes
were proposed based on the 12 molecular clades and associated morphology:
Apogonichthyini, Apogonini (mainly including species of Apogon sensu stricto),
Archamiini, Cheilodipterini, Gymnapogonini, Ostorhinchini (including striped
species of recent Ostorhinchus), Pristiapogonini, Rhabdamiini, Sphaeramiini
(mainly including barred species of traditional Ostorhinchus, such as
Apogonichthyoides, Jaydia and Nectamia), Siphamiini, Veruluxini, and Zoramiini.
Two additional tribes are proposed based only on morphology: Glossamiini and
Lepidamiini. For each of the 14 tribes, morphological characters were described.
One new genus, Fibramia, type species Apogon thermalis, recently in Ostorhinchus,
was described supported by morphology and molecular trees. A key to all genera is
provided and all valid and uncertain status species are allocated to tribes and
genera.
PMID- 25112247
TI - Additions to the Nepticulidae (Lepidoptera) of East Asia, with descriptions of
three new species from Primorskiy Kray.
AB - Stigmella multispicata Rociene & Stonis, sp. nov., S. sexcornuta Rociene &
Stonis, sp. nov., and Ectoedemia paraortiva Rociene & Stonis, sp. nov. are
described from Primorskiy Kray (Russian Far East). The new species are
illustrated with photographs and drawings of the adults and genitalia. Stigmella
thuringiaca (Petry), a species previously known only from West Palaearctic, is
here newly recorded in East Asia. The male genitalia of the little known
Stigmella gimmonella (Matsumura) are illustrated for the first time with
photographs; the male genital morphology of two other species, S. tranocrossa
Kemperman & Wilkinson and Ectoedemia philipi Puplesis, is updated and newly
documented. A chart of chorological composition of the Nepticulidae currently
known in East Asia is provided.
PMID- 25112248
TI - First evidence of cynipids from the Oceanian Region: the description of
Lithonecrus papuanus a new genus and species of cynipid inquiline from Papua New
Guinea (Hymenoptera: Cynipidae, Synergini).
AB - Lithonecrus papuanus Nieves-Aldrey & Butterill, a new genus and species of
inquiline oak gall wasps (Hymenoptera: Cynipidae: Synergini), is described from
material reared from galls on Lithocarpus celebicus (Miq.) Rehd., collected in
Papua New Guinea. The new genus and species is the first record of a cynipid from
Papua New Guinea and the whole Oceanian biogeographic region, and represents
the easternmost oriental record of a cynipid wasp (Hymenoptera: Cynipidae). The
new genus is similar to Saphonecrus Dalla Torre & Kieffer, and to the recently
described Lithosaphonecrus Tang, Melika & Bozso, but differs from these genera in
several important diagnostic characters. Taxonomic affinities and differences
with related genera and species and biogeographical implications are discussed.
PMID- 25112249
TI - Pethia longicauda, a new species of barb (Teleostei: Cyprinidae) from the
northern Western Ghats, India.
AB - Pethia longicauda, a new cyprinid fish, is described from Hiranyakeshi River,
Krishna drainage, Maharashtra, India. It can be distinguished from congeners
based on a combination of characters including: a long caudal peduncle,
incomplete lateral line, absence of barbels, upper lip thick and fleshy, distinct
lateral fold on snout, 22-24 scales in lateral series, 5-6 lateral-line pored
scales, nine predorsal scales, 9-10 prepelvic scales, 15-17 preanal scales,
1/23/1/31/2 transverse scales, 11-15 pairs of serrae on the distal half of the
last unbranched dorsal-fin ray, 11-13 branched pectoral fin rays, 4+26 total
vertebrae, 4+5 predorsal vertebrae, 4+13 abdominal and 13 caudal vertebrae, body
iridescent silver in color with a black humeral spot, two black blotches on
caudal peduncle and dorsal fin usually without any color bands or blotches but in
breeding males with two rows of minute, indistinct black spots.
PMID- 25112250
TI - A taxonomic revision of boas (Serpentes: Boidae).
PMID- 25112251
TI - Two new Aprostocetus species (Hymenoptera: Eulophidae: Tetrastichinae),
fortuitous parasitoids of invasive eulophid gall inducers (Tetrastichinae) on
Eucalyptus and Erythrina.
AB - Two closely related new species of Aprostocetus Westwood (Hymenoptera:
Eulophidae: Tetrastichinae) are described as fortuitous parasitoids of invasive
gall inducers in two other genera of Tetrastichinae, Leptocybe Fisher & LaSalle
and Quadrastichus Girault. Aprostocetus causalis La Salle & Wu is a parasitoid of
Leptocybe invasa Fisher & La Salle on Eucalyptus spp. (Myrtaceae) in China and
Thailand, and A. felix La Salle, Yang & Lin is a parasitoid of Quadrastichus
erythrinae Kim on Erythrina spp. (Fabaceae) in Taiwan. Epitetrastichus
nigriventris Girault, 1913 is removed from synonymy from Aprostocetus gala
(Walker), and treated as the valid species A. nigriventris (Girault).
PMID- 25112252
TI - The genus Nyctiophylax Brauer in China (Trichoptera, Polycentropodidae).
AB - Currently, 8 species of the genus Nyctiophylax Brauer are known from China.
Examination of material collected from Guangdong, Guangxi, Jiangxi and Sichuan
Provinces during 2004-2005 has revealed 4 new species and 2 new records of this
genus, bringing the number of Chinese Nyctiophylax species to 14. Newly described
species include: Nyctiophylax (Paranyctiophylax) crinalis n. sp., N. (P.)
dactylatus n. sp., N. (P.) orbicularis n. sp., and N. (P.) macrorrhinus n. sp.
Nyctiophylax (Paranyctiophylax) sagax Mey and N. (N.) amphonion Malicky &
Chantaramongkol are newly recorded for the Chinese fauna, which are re
illustrated and re-described for clear comparisons. The additional collection
sites for the previously described species are provided.
PMID- 25112253
TI - Two new species of Syrphidae (Diptera) from Chukotka (Northern Russian Far East).
AB - Two new species, Platycheirus beringiensis sp. n. and Cheilosia chukotana sp. n.,
are described from Chukotka (northern part of Russian Far East). The new
Platycheirus is close to Platycheirus immarginatus (Zetterstedt), but differing
by the following characters: fore tibia with a black stripe on posterior side;
mid-femur without fine black curved hairs directed to the base of the femur; mid
tibia without long anteroventral hairs; abdomen black with fine brownish lustre
on tergites. The new Cheilosia species is close to Ch. semifasciata Becker, but
differs by its characteristic sharply raised central knob, and by lack of
transversal stripe and indentation in anterior third of frons.
PMID- 25112254
TI - Two new species of quill mites of the family Syringophilidae (Acariformes:
Cheyletoidea) associated with treronine doves (Columbiformes: Columbidae:
Treroninae).
AB - Two new species of quill mites (Acariformes: Syringophilidae) associated with
doves of the subfamily Treroninae (Columbiformes: Columbidae) from the Oceanian
realm are described: Gunabopicobia masalaje sp. nov. from six avian host species,
Ptilinopus iozonus Gray (type host) Ducula pistrinaria (Bonaparte), D. rosacea
(Temminck), D. rufigaster (Quoy and Gaimard), D. spilorrhoa (Gray), D. luctuosa
(Temminck), and Peristerophila lature sp. nov. also from six host species Ducula
luctuosa (type host ), D. spilorrhoa, Ptilinopus jambu Gmelin, P. melanospilus
Salvadori, P. porphyreus Temminck, P. regina Swainson. Additionally, Treron
waalia (Meyer) is noted as a new host species for Meitingsunes columbicus Glowska
and Skoracki, 2010.
PMID- 25112255
TI - Species-richness in the Oriental fungus-feeding thrips of the genus Azaleothrips
(Thysanoptera, Phlaeothripidae).
AB - Azaleothrips, a phlaeothripine genus of fungus-feeding species, is presumably
endemic to the Oriental Region between India and Japan. Although only 10 species
have been known in this genus until now, a total of 35 species is recorded here,
of which 26 are newly described: from Indonesia--A. bali sp.n., A. bulelengi
sp.n., A. dentatus sp.n., A. dorsalis sp.n., A. floresi sp.n., A. inflavus sp.n.,
A. simulans sp.n., A. sulawesicus sp.n., from the Philippines--A. apoensis sp.n.,
A. bifidius sp.n., A. luzonensis sp.n., A. mindanaoensis sp.n., A. philippinensis
sp.n., from Taiwan--A. atayal sp.n., A. formosae sp.n., A. taiwanus sp.n., from
Thailand--A. flavicollis sp.n., A. phuketanus sp.n., A. pulcher sp.n., A.
toshifumii sp.n., from Vietnam--A. laocai sp.n., A. vietnamensis sp.n., from W.
Malaysia--A. malaya sp.n., A. reticulatus sp.n., A. richardi sp.n., A. templeri
sp.n. In addition A. magnus Chen, described from Taiwan, is newly synonymized
with A. moundi. Azaleothrips laevigatus, described from southern Japan, is newly
recorded more widely in Southeast Asia. A key to 33 species is provided, but A.
bhattii and A. lineus cannot be recognized because of the poor information in the
original descriptions.
PMID- 25112256
TI - A new diminutive frog species of Adelophryne (Amphibia: Anura:
Eleutherodactylidae) from the Atlantic Forest, southeastern Brazil.
AB - The genus Adelophryne is composed of diminutive frogs occurring in northern
Amazonia and the Atlantic Forest. Herein we describe a new species of Adelophryne
found in the leaf litter of primary and secondary forests in the mountainous
region of Espirito Santo state, southeastern Brazil. The new species is
characterized by its small body size, two phalanges in the finger IV, and a
glandular ridge line that runs from the posterior part of eye to the insertion of
the forelimb. This species is sensitive to edge effect and conversion of native
forest into coffee and Eucalyptus plantations and may be listed as Endangered
(EN) under B1ab(iii) criteria of the IUCN Red List.
PMID- 25112257
TI - New species of Pseudonannolene Silvestri, 1895 from Brazilian limestone caves
with comments on the potential distribution of the genus in South America
(Spirostreptida: Pseudonannolenidae).
AB - Ten new species of Pseudonannolene Silvestri, 1895 are described from Brazilian
limestone caves. The species are separated by the morphology of their gonopods
and the processes of the first pair of legs of males. A pictorial identification
key for the cave-dwelling species from Brazil is provided, besides comments on
the distribution of the genus with a potential distribution map of
Pseudonannolene and Epinannolene in South and Central America.
PMID- 25112258
TI - A re-description of rare alpheid shrimp Amphibetaeus jousseaumei (Coutiere, 1896)
and escription of a new species of the genus Athanopsis Coutiere, 1897(Crustacea:
Decapoda: Alpheidae) from Iranian coast of the Persian Gulf.
AB - A new record of rare alpheid shrimp Amphibetaeus jousseaumei (Coutiere, 1896)
(Decapoda: Caridea: Alpheidae) is presented based on material collected from
Qeshm Island, Iran, the Persian Gulf. This is the first record of the species for
the Iranian waters as well as the second record and re-description of A.
jousseaumei from its original description given by Coutiere (1896). Besides, a
new alpheid shrimp species Athanopsis tarahomii sp. nov. is described from the
same locality. The new species can be clearly separated from all remaining
species of the genus Athanopsis by deep rostrum curved downward and the presence
of well marked blunt extra-cornea tooth on carapace.
PMID- 25112259
TI - Taxonomic utility of niche models in validating species concepts: A case study in
Anthophora (Heliophila) (Hymenoptera: Apidae).
AB - Taxonomy has far-reaching effects throughout biology, and incorrect taxonomy can
be detrimental in many ways. Polymorphic species complexes, many of which exist
in the bee genus Anthophora Latreille, lend themselves to such difficulties. This
study employs environmental niche mapping (ENM) and traditional morphological
analyses to investigate the validity of the subjective synonymy of Anthophora
(Heliophila) curta Provancher with the senior synonym A. squammulosa Dours.
Eleven of fifty morphological characters consistently differentiate the two
putative species, with an additional five characters sometimes separating them.
Additionally, based on over 1000 georeferenced museum specimens, the geographic
ranges of the two taxa do not overlap. The two entities also react differently to
the bioclimatic variables based on correlation analysis. We further tested the
two-species hypothesis by constructing ENMs with informative bioclimatic
variables associated with locality records. Their modelled distributions
overlapped less than 1%, suggesting discrete environmental boundaries. The
variables which contributed most to each species' model also differed. These
differences are explored in relation to their habitats. The combined
morphological and biogeographic analysis indicates that A. curta and A.
squammulosa are distinct species. Based on the accumulated evidence the synonymy
is formally rejected and A. curta is recognized as a valid species. Five
additional taxa (A. bispinosa Cockerell, A. franciscana Cockerell, A. usticauda
Cockerell, A. u. cinerior Cockerell, A. zamoranella Cockerell) are newly
synonymized with A. squammulosa and Anthophora curta var. melanops Cockerell is
newly synonymized with A. curta. Implications outside of taxonomy are discussed.
PMID- 25112260
TI - Description of Ektaphelenchoides fuchsi n. sp. (Nematoda: Ektaphelenchinae) from
western Iran.
AB - Ektaphelenchoides fuchsi n. sp., recovered from a soil sample around the
rhizosphere of Cucurbita maxima in western Iran, is described and illustrated
based on morphological and molecular characters. The new species is characterized
by its body length of 529-712 um, continuous lip region, lateral fields with
three incisures, total stylet length of 14-18 um with rounded basal knobs,
excretory pore 70-84 um and hemizonid 87-96 um from the anterior end, post
uterine sac short, 6-9 um long in female and tail conoid with long filiform
terminus in male. Based on morphological and molecular characters, the new
species is close to E. kelardashtensis, E. attenuata, and E. musae. It differs
from the closest species E. kelardashtensis by its longer sylet (14-18 vs 13-16
um) and stylet with basal knobs vs not, longer post uterine sac (6-9 vs 3-6 um),
more posterior position of excretory pore and hemizonid (70-84 vs 55-66 and 87-96
vs 67-78 um, respectively), and longer spicules (12-13 vs 8-10 um). Comparisons
with other species of Ektaphelenchoides are also discussed. Molecular analyses
were performed based on 631 bp of the partial ribosomal RNA large subunit gene
(D2/D3 of LSU) and showed that E. fuchsi n. sp. is unique when compared with
other species of the genus for which sequences of that region are available.
PMID- 25112261
TI - Laomenes albonigrus sp. nov., (Crustacea: Decapoda; Pontoniinae) from Ashmore
Reef, Western Australia.
AB - One specimen of an un-described species of pontoniine shrimp of the genus
Laomenes Clark, 1919, Laomenes albonigrus sp. nov., was collected from a crinoid
host from Ashmore Reef, Western Australia, and is now described and illustrated.
PMID- 25112262
TI - Grammoplites vittatus (Valenciennes), (Scorpaeniformes, Platycephalidae), removed
from synonymy with Grammoplites scaber (Linnaeus).
AB - Grammoplites vittatus (Valenciennes), often previously overlooked by authors or
regarded as a junior synonym of G. scaber (Linnaeus), is shown here to be a valid
species. It has more gill rakers (7-8) then G. scaber and G. knappi (usually 6)
and a narrower interorbital width than G. scaber. A key to the species of
Grammoplites Fowler is given.
PMID- 25112263
TI - A phylogenetic analysis of the southern African gecko genus Afroedura Loveridge
(Squamata: Gekkonidae), with the description of nine new species from Limpopo and
Mpumalanga provinces of South Africa.
AB - A molecular phylogeny of the largely rupicolous geckos of the gekkonid genus
Afroedura is presented based on a combination of mitochondrial and nuclear gene
sequence data. Previously recognized species groups are only partly recovered,
with A. pondolia retrieved as very distantly related to the congeners to which it
was previously considered allied. Afroedura hawequensis forms a monotypic group
that is sister to all other species, which are allocated to the A. nivaria, A.
transvaalica, A. africana, A. multiporis, A. marleyi, and A. langi groups. The
taxonomic status of species occurring in the former Transvaal province of South
Africa (now Limpopo and Mpumalanga provinces) is reviewed based on morphological
and molecular evidence. Afroedura rupestris sp. nov. is described in the A.
multiporis group, A. maripi sp. nov., A. pongola sp. nov., and A. rondavelica sp.
nov., are described in the A. marleyi group, and A. broadleyi sp. nov., A.
granitica sp. nov., A. leoloensis sp. nov., A. pienaari sp. nov., and A.
waterbergensis sp. nov. are described in the A. langi group. In addition, A.
haackei, A. namaquensis, and A. tirasensis, are all raised to specific status.
The description of nine new species highlights Limpopo and Mpumalanga provinces
as previously unrecognized centers of diversity for the genus Afroedura. A key to
the species of Afroedura is provided.
PMID- 25112264
TI - Revision of opeatocerata melander, 1928 (Diptera: empididae: empidinae).
AB - The species of the Neotropical genus Opeatocerata Melander are revised to include
21 species, with fifteen species described as new: O. agudeloi sp. nov., O.
ampullaria sp. nov., O. bare sp. nov., O. brasiliensis sp. nov., O.
chaetohypandrialis sp. nov., O. cylindrophallus sp. nov., O. curvipenis sp. nov.,
O. hadrophallus sp. nov., O. megalophallus sp. nov., O. mourai sp. nov., O.
nhamunda sp. nov., O. smithi sp. nov., O. spinipenis sp. nov., O. tanimboca sp.
nov. and O. zuleideae sp. nov. All species are described and male and female
genitalia illustrated. An identification key and the geographic distributions of
the species are also presented.
PMID- 25112265
TI - Plant mites of the Dominican Republic, with a description of a new species of
Petrobia (Tetranychina) Wainstein, 1960 (Acari, Prostigmata, Tetranychidae) and a
key to the species of this subgenus.
AB - Fourteen mite species of plant-associated mites of the suborder Prostigmata are
reported from the Dominican Republic. Four of these refer to new findings for the
country, including Petrobia (Tetranychina) hispaniola n. sp. Sanchez &
Flechtmann, described from specimens collected from leaves of Citrus sp.
(Rutaceae) and Rosa sp. (Rosaceae). A key for the separation of the world species
of Petrobia (Tetranychina) is presented.
PMID- 25112266
TI - The genus Mytilina in China, with description of a new species (Rotifera:
Monogononta: Mytilinidae).
AB - During our study of biodiversity of Rotifera in PR China, as model taxon of
freshwater Micrometazoa, we came across several records that warrant revision
regarding species of genus Mytilina Bory de St. Vincent, 1826 (Rotifera,
Monogonta, Mytilinidae). In addition to this review we describe a new species
encountered during examination of freshwater habitats of Inner Mongolia,
P.R.China. This new species, Mytilina wangi n. sp., appears to belong to the
Mytilina mucronata - ventralis complex but differs from the known taxa in the
group by its domed lorica and relatively short toes. We provide an annotated
checklist of the Chinese representatives of the genus and discuss the species of
the M. mucronata-ventralis group. We suggest treating M. brevispina (Ehrenberg,
1830) and M. ventralis (Ehrenberg, 1830)(synonym: M. macracantha (Gosse, 1886))
as separate species-level taxa rather than as two infrasubspecific variants of
the same species, and argue that Mytilina trigona var. bispinosa Wang, 1961 is a
misidentified M. acanthophora Hauer, 1938 rather than an infrasubspecific variant
of M. trigona (Gosse, 1851).
PMID- 25112267
TI - A new species of Hypoaspis Canestrini from Iran (Acari: Laelapidae), with a key
to the species occurring in the Western Palaearctic Region.
AB - Hypoaspis elegans sp. nov. was collected on adult female Oryctes elegans Prell.
(Coleoptera: Scarabaeidae) in Bam, Kerman province, Iran. The new species is
described and illustrated from adult females. Hypoaspis surii Khanjani et. al.,
2013 is a junior synonym of Hypoaspis maryamae Joharchi & Halliday, 2011. A key
to the Western Palaearctic species of Hypoaspis is presented.
PMID- 25112268
TI - Description of Hylopanchax paucisquamatus (Cyprinodontiformes: Poeciliidae), a
new lampeye species from the Odzala-Kokoua National Park, Republic of Congo.
AB - A new deep-bodied Hylopanchax species is described from the northwestern Congo
basin. Hylopanchax paucisquamatus, new species, was collected in the Odzala
Kokoua National Park in the Likouala River drainage of the Republic of Congo. It
differs from its congeners, including the deep-bodied H. leki and H. ndeko, by a
unique combination of morphological characters, including low number of mid
longitudinal and transverse scales, number of dorsal-fin rays, and position of
dorsal-fin origin in relation to anal-fin. It is the only deep-bodied species
currently known outside the Kasai River drainage.
PMID- 25112269
TI - Ceriomicrodon petiolatus Hull, 1937 (Diptera, Syrphidae, Microdontinae):
Redescription and new records.
AB - The monotypic genus Ceriomicrodon Hull, 1937 was known in the current literature
by a few specimens, all from Brazil but with records only for Mato Grosso and
Roraima states. The only species of the genus is here redescribed including the
description of the female and its terminalia, in addition to a preliminary
description of the egg. Images of male and female genitalia and egg are provided.
New Brazilian records for Amazonas, Maranhao and Rondonia and a brief diagnosis
to distinguish that genus from other similar Microdontinae genera are presented.
PMID- 25112270
TI - New and little known bees of the genus Colletes Latreille 1802 (Hymenoptera:
Colletidae) from Central Asia.
AB - In addition to a previously published study about Central Asian Colletes bees we
here further report on nine rarely collected and little known species. Now 85
species of Colletes are known from this region with three of them recorded for
the first time: C. asiaticus Kuhlmann 1999, C. iranicus Noskiewicz 1962 and C.
succinctus (Linnaeus 1758). Colletes pseudomirabilis sp. nov. is described from
Turkmenistan.
PMID- 25112271
TI - One new species of the genus Alloteratura Hebard, 1922 (Orthoptera:
Tettigoniidae: Meconematinae) from Yunnan, China.
AB - The paper describes one new species of the genus Alloteratura Hebard, 1922 from
Yunnan, China, i.e. Alloteratura quaternispina, sp. nov.
PMID- 25112272
TI - Cross-cultural adaptation and reliability and validity of the Dutch Patient-Rated
Tennis Elbow Evaluation (PRTEE-D).
AB - BACKGROUND: Lateral Epicondylalgia (LE) is a common injury for which no reliable
and valid measure exists to determine severity in the Dutch language. The Patient
Rated Tennis Elbow Evaluation (PRTEE) is the first questionnaire specifically
designed for LE but in English. The aim of this study was to translate into Dutch
and cross-culturally adapt the PRTEE and determine reliability and validity of
the PRTEE-D (Dutch version). METHODS: The PRTEE was cross-culturally adapted
according to international guidelines. Participants (n = 122) were asked to fill
out the PRTEE-D twice with a one week interval to assess test-retest reliability.
Internal consistency of the PRTEE-D was determined by calculating Crohnbach's
alphas for the questionnaire and subscales. Intraclass Correlation Coefficients
(ICC) were calculated for the overall PRTEE-D score, pain and function subscale
and individual questions to determine test-retest reliability. Additionally, the
Disabilities for the Arm, Shoulder and Hand questionnaire (DASH) and Visual
Analogue Scale (VAS) pain scores were obtained from 30 patients to assess
construct validity; Spearman's correlation coefficients were calculated between
the PRTEE-D (subscales) and DASH and VAS-pain scores. RESULTS: The PRTEE was
successfully cross-culturally adapted into Dutch (PRTEE-D). Crohnbach's alpha for
the first assessment of the PRTEE-D was 0.98; Crohnbach's alpha was 0.93 for the
pain subscale and 0.97 for the function subscale. ICC for the PRTEE-D was 0.98;
subscales also showed excellent ICC values (pain scale 0.97 and function scale
0.97). A significant moderate correlation exists between PRTEE-D and DASH (0.65)
and PRTEE-D and VAS pain (0.68). CONCLUSION: The PRTEE was successfully cross
culturally adapted and this study showed that the PRTEE-D is reliable and valid
to obtain an indication of severity of LE. An easy-to-use instrument for
practitioners is now available and this facilitates comparing Dutch and
international research data.
PMID- 25112273
TI - Decision support system for age-related macular degeneration using discrete
wavelet transform.
AB - Age-related macular degeneration (AMD) affects the central vision and
subsequently may lead to visual loss in people over 60 years of age. There is no
permanent cure for AMD, but early detection and successive treatment may improve
the visual acuity. AMD is mainly classified into dry and wet type; however, dry
AMD is more common in aging population. AMD is characterized by drusen, yellow
pigmentation, and neovascularization. These lesions are examined through visual
inspection of retinal fundus images by ophthalmologists. It is laborious, time
consuming, and resource-intensive. Hence, in this study, we have proposed an
automated AMD detection system using discrete wavelet transform (DWT) and feature
ranking strategies. The first four-order statistical moments (mean, variance,
skewness, and kurtosis), energy, entropy, and Gini index-based features are
extracted from DWT coefficients. We have used five (t test, Kullback-Lieber
Divergence (KLD), Chernoff Bound and Bhattacharyya Distance, receiver operating
characteristics curve-based, and Wilcoxon) feature ranking strategies to identify
optimal feature set. A set of supervised classifiers namely support vector
machine (SVM), decision tree, [Formula: see text]-nearest neighbor ([Formula: see
text]-NN), Naive Bayes, and probabilistic neural network were used to evaluate
the highest performance measure using minimum number of features in classifying
normal and dry AMD classes. The proposed framework obtained an average accuracy
of 93.70%, sensitivity of 91.11%, and specificity of 96.30% using KLD ranking and
SVM classifier. We have also formulated an AMD Risk Index using selected features
to classify the normal and dry AMD classes using one number. The proposed system
can be used to assist the clinicians and also for mass AMD screening programs.
PMID- 25112274
TI - Evaluation of the hemodynamics in straight 6-mm and tapered 6- to 8-mm grafts as
upper arm hemodialysis vascular access.
AB - The present study is intended to investigate and compare the hemodynamics in two
different sizes of hemodialysis arteriovenous grafts for upper arm hemodialysis
vascular access: 8-mm tapered to 6-mm at the arterial side and straight 6 mm. A
computational simulation approach is presented for this study, which is validated
against the available experimental and numerical pressure measurements in the
literature. The imposed boundary conditions at the arterial inlet and venous
outlet boundaries of the models are physiological velocity and pressure
waveforms, respectively. Blood flow fields and distribution patterns of the
hemodynamic indices including wall shear stress (WSS) as one of the major
hemodynamic parameters of the cardiovascular system and spatial wall shear stress
gradient (SWSSG) as an indicator of disturbed flow patterns and hence susceptible
sites of lesion developments are analyzed and compared between the two grafts.
The tapered 6- to 8-mm graft seemingly is associated with less disturbed flow
patterns within the venous anastomosis (VA) and the vein downstream while
benefiting from higher blood flow rates within. Also, it shows a definitive
advantage in terms of WSS and SWSSG distribution patterns around the VA and
throughout the vein downstream with significantly lower values, which reduce the
risk of thrombosis formation and stenotic lesion developments. The only
disadvantage encountered in using 6- to 8-mm tapered graft is higher values of
hemodynamic parameters at the arterial junction attributable to its significantly
higher mean blood flow rate within. The results clearly indicate that the tapered
6- to 8-mm graft entirely outperforms straight 6-mm graft hemodynamically as an
upper arm hemodialysis vascular access graft and confirms clinical data in the
literature, which suggests advantageous use of tapered 6- to 8-mm grafts in the
creation of upper arm brachioaxillary hemodialysis vascular access grafts in
selected groups of patients with expectably higher patency rates and lower
complications.
PMID- 25112276
TI - Gene mutation may increase risk of breast cancer by up to nine times.
PMID- 25112275
TI - Platelets promote mitochondrial uncoupling and resistance to apoptosis in
leukemia cells: a novel paradigm for the bone marrow microenvironment.
AB - Here we report that leukemia cell lines and primary CD34+ leukemic blasts exposed
to platelet rich plasma (PRP) or platelet lysates (PL) display increased
resistance to apoptosis induced by mitochondria-targeted agents ABT-737 and CDDO
Me. Intriguingly, leukemia cells exposed to platelet components demonstrate a
reduction in mitochondrial membrane potential (DeltaPsiM) and a transient
increase in oxygen consumption, suggestive of mitochondrial uncoupling.
Accompanying the ranolazine-sensitive increase in oxygen consumption, a reduction
in triglyceride content was also observed in leukemia cells cultured with
platelet components indicating that lipolysis and fatty acid oxidation may
support the molecular reduction of oxygen in these cells. Mechanistically,
platelet components antagonized Bax oligomerization in accordance with previous
observations supporting an antiapoptotic role for fatty acid oxidation in
leukemia cells. Lastly, substantiating the notion that mitochondrial uncoupling
reduces oxidative stress, platelet components induced a marked decrease in basal
and rotenone-induced superoxide levels in leukemia cells. Taken together, the
decrease in DeltaPsiM, the transient increase in ranolazine-sensitive oxygen
consumption, the reduction in triglyceride levels, and the reduced generation of
superoxide, all accompanying the increased resistance to mitochondrial apoptosis,
substantiate the hypothesis that platelets may contribute to the chemoprotective
sanctuary of the bone marrow microenvironment via promotion of mitochondrial
uncoupling.
PMID- 25112277
TI - Male genital mutilation (amputation) and its complications: a case report.
AB - BACKGROUND: Genital losses from ritual attacks are often reported in the media
and often discussed in the social media but are hardly reported in medical
literature. Male genital mutilation (MGM) refers to permanent modification of the
external genitalia that involves ablation of genital tissues.When found, it is
usually as a consequence of poor circumcision skills, auto mutilation/castration
or genital injuries caused by attacks or accidents. Male circumcision on its own
is widely regarded as a rather safe and acceptable practice which is known to
have some health benefits and in keeping with several religious customs as rite
of passage. Outside of professional performed circumcision, MGM is usually
associated with dark arts and malicious intentions like witchcraft or as a
consequence of torture of prisoners of war for information. CASE PRESENTATION: In
this case we describe a 5-year old Ugandan boy who had his genitals mutilated in
bizarre circumstances within a ritual attack. He survived and a urethrostomy was
fashioned. CONCLUSION: There is need to document more of these cases in order to
gather enough information to inform prevention and treatment strategies. Issues
of hormonal replacement therapy (HRT) and possible sex change require much
debate. These genital sex changing operations should preferably be avoided until
a child can fully participate in decision making.
PMID- 25112278
TI - Nonlesions, misdiagnoses, missed diagnoses, and other interpretive challenges in
fish histopathology studies: a guide for investigators, authors, reviewers, and
readers.
AB - Differentiating salient histopathologic changes from normal anatomic features or
tissue artifacts can be decidedly challenging, especially for the novice fish
pathologist. As a consequence, findings of questionable accuracy may be reported
inadvertently, and the potential negative impacts of publishing inaccurate
histopathologic interpretations are not always fully appreciated. The objectives
of this article are to illustrate a number of specific morphologic findings in
commonly examined fish tissues (e.g., gills, liver, kidney, and gonads) that are
frequently either misdiagnosed or underdiagnosed, and to address related issues
involving the interpretation of histopathologic data. To enhance the utility of
this article as a guide, photomicrographs of normal and abnormal specimens are
presented. General recommendations for generating and publishing results from
histopathology studies are additionally provided. It is hoped that the furnished
information will be a useful resource for manuscript generation, by helping
authors, reviewers, and readers to critically assess fish histopathologic data.
PMID- 25112279
TI - Pharmacological inhibition of DGAT1 induces sebaceous gland atrophy in mouse and
dog skin while overt alopecia is restricted to the mouse.
AB - Diacylglycerol O-acyltransferase 1 (DGAT1) plays an important role in
synthesizing lipids, and inhibitors of DGAT1 have been investigated as potential
treatments for diabetes and metabolic diseases. DGAT1 knockout (-/-) mice are
resistant to obesity, have increased sensitivity to insulin, and exhibit
sebaceous gland atrophy and alopecia. Prolonged pharmacological inhibition of
DGAT1 with AZD7687 in mice results in the same skin phenotype, including
sebaceous gland atrophy and alopecia, as seen in the skin of DGAT1 (-/-) mice.
AZD7687-mediated effects on the skin were dose- and time-dependent and
reversible. They occurred only at substantial levels of continuous DGAT1
inhibition. Prolonged treatment of dogs with AZD7687 also resulted in sebaceous
gland atrophy but did not result in the more adverse skin changes of hair loss
and skin lesions. Our findings highlight a significant risk of generating the
same lesions that were seen in mouse skin during clinical development of DGAT1
inhibitors in humans and also reveal a species difference in the effects on the
skin, indicating that the mouse may be an especially sensitive species.
Therefore, although human therapeutic doses may not have the same influence on
skin morphology as seen in mice, monitoring of skin changes will be essential in
clinical trials with DGAT1 inhibitors.
PMID- 25112281
TI - The Relationship between Perceptual Decision Variables and Confidence in the
Human Brain.
AB - Perceptual confidence refers to the degree to which we believe in the accuracy of
our percepts. Signal detection theory suggests that perceptual confidence is
computed from an internal "decision variable," which reflects the amount of
available information in favor of one or another perceptual interpretation of the
sensory input. The neural processes underlying these computations have, however,
remained elusive. Here, we used fMRI and multivariate decoding techniques to
identify regions of the human brain that encode this decision variable and
confidence during a visual motion discrimination task. We used observers' binary
perceptual choices and confidence ratings to reconstruct the internal decision
variable that governed the subjects' behavior. A number of areas in prefrontal
and posterior parietal association cortex encoded this decision variable, and
activity in the ventral striatum reflected the degree of perceptual confidence.
Using a multivariate connectivity analysis, we demonstrate that patterns of brain
activity in the right ventrolateral prefrontal cortex reflecting the decision
variable were linked to brain signals in the ventral striatum reflecting
confidence. Our results suggest that the representation of perceptual confidence
in the ventral striatum is derived from a transformation of the continuous
decision variable encoded in the cerebral cortex.
PMID- 25112280
TI - The distribution of insertionally polymorphic endogenous retroviruses in breast
cancer patients and cancer-free controls.
AB - BACKGROUND: Integration of retroviral DNA into a germ cell can result in a
provirus that is transmitted vertically to the host's offspring. In humans, such
endogenous retroviruses (HERVs) comprise >8% of the genome. The HERV-K(HML-2)
proviruses consist of ~90 elements related to mouse mammary tumor virus, which
causes breast cancer in mice. A subset of HERV-K(HML-2) proviruses has some or
all genes intact, and even encodes functional proteins, though a replication
competent copy has yet to be observed. More than 10% of HML-2 proviruses are
human-specific, having integrated subsequent to the Homo-Pan divergence, and, of
these, 11 are currently known to be polymorphic in integration site with variable
frequencies among individuals. Increased expression of the most recent HML-2
proviruses has been observed in tissues and cell lines from several types of
cancer, including breast cancer, for which expression may provide a meaningful
marker of the disease. RESULTS: In this study, we performed a case-control
analysis to investigate the possible relationship between the genome-wide
presence of individual polymorphic HML-2 proviruses with the occurrence of breast
cancer. For this purpose, we screened 50 genomic DNA samples from individuals
diagnosed with breast cancer or without history of the disease (n = 25 per group)
utilizing a combination of locus-specific PCR screening, in silico analysis of
HML-2 content within the reference human genome sequence, and high-resolution
genomic hybridization in semi-dried agarose. By implementing this strategy, we
were able to analyze the distribution of both annotated and previously
undescribed polymorphic HML-2 proviruses within our sample set, and to assess
their possible association with disease outcome. CONCLUSIONS: In a case-control
analysis of 50 humans with regard to breast cancer diagnosis, we found no
significant difference in the prevalence of proviruses between groups, suggesting
common polymorphic HML-2 proviruses are not associated with breast cancer. Our
findings indicate a higher level of putatively novel HML-2 sites within the
population, providing support for additional recent insertion events, implying
ongoing, yet rare, activities. These findings do not rule out either the
possibility of involvement of such proviruses in a subset of breast cancers, or
their possible utility as tissue-specific markers of disease.
PMID- 25112282
TI - Control of Spontaneous Ca2+ Transients Is Critical for Neuronal Maturation in the
Developing Neocortex.
AB - Neural activity plays roles in the later stages of development of cortical
excitatory neurons, including dendritic and axonal arborization, remodeling, and
synaptogenesis. However, its role in earlier stages, such as migration and
dendritogenesis, is less clear. Here we investigated roles of neural activity in
the maturation of cortical neurons, using calcium imaging and expression of
prokaryotic voltage-gated sodium channel, NaChBac. Calcium imaging experiments
showed that postmigratory neurons in layer II/III exhibited more frequent
spontaneous calcium transients than migrating neurons. To test whether such an
increase of neural activity may promote neuronal maturation, we elevated the
activity of migrating neurons by NaChBac expression. Elevation of neural activity
impeded migration, and induced premature branching of the leading process before
neurons arrived at layer II/III. Many NaChBac-expressing neurons in deep cortical
layers were not attached to radial glial fibers, suggesting that these neurons
had stopped migration. Morphological and immunohistochemical analyses suggested
that branched leading processes of NaChBac-expressing neurons differentiated into
dendrites. Our results suggest that developmental control of spontaneous calcium
transients is critical for maturation of cortical excitatory neurons in vivo:
keeping cellular excitability low is important for migration, and increasing
spontaneous neural activity may stop migration and promote dendrite formation.
PMID- 25112283
TI - Functional two-way analysis of variance and bootstrap methods for neural
synchrony analysis.
AB - BACKGROUND: Pairwise association between neurons is a key feature in
understanding neural coding. Statistical neuroscience provides tools to estimate
and assess these associations. In the mammalian brain, activating ascending
pathways arise from neuronal nuclei located at the brainstem and at the basal
forebrain that regulate the transition between sleep and awake neuronal firing
modes in extensive regions of the cerebral cortex, including the primary visual
cortex, where neurons are known to be selective for the orientation of a given
stimulus. In this paper, the estimation of neural synchrony as a function of time
is studied in data obtained from anesthetized cats. A functional data analysis of
variance model is proposed. Bootstrap statistical tests are introduced in this
context; they are useful tools for the study of differences in synchrony strength
regarding 1) transition between different states (anesthesia and awake), and 2)
affinity given by orientation selectivity. RESULTS: An analysis of variance model
for functional data is proposed for neural synchrony curves, estimated with a
cross-correlation based method. Dependence arising from the experimental setting
needs to be accounted for. Bootstrap tests allow the identification of
differences between experimental conditions (modes of activity) and between pairs
of neurons formed by cells with different affinities given by their preferred
orientations. In our test case, interactions between experimental conditions and
preferred orientations are not statistically significant. CONCLUSIONS: The
results reflect the effect of different experimental conditions, as well as the
affinity regarding orientation selectivity in neural synchrony and, therefore, in
neural coding. A cross-correlation based method is proposed that works well under
low firing activity. Functional data statistical tools produce results that are
useful in this context. Dependence is shown to be necessary to account for, and
bootstrap tests are an appropriate method with which to do so.
PMID- 25112284
TI - An unusual case of abdominal distension with constipation.
PMID- 25112285
TI - Annual review of children with tuberous sclerosis.
AB - Tuberous sclerosis complex is a complex childhood disorder characterised by the
formation of hamartomas in multiple organs. Annual review of this disease is
recommended to monitor the development of complications. We aim to provide a
concise, evidence-based framework to assist clinicians during this annual review.
We focus on the following areas: (A) what questions need to be asked during
annual review, (B) which areas need emphasis on examination, (C) when is an
investigation required and (D) referral to tertiary specialists and other members
of the multidisciplinary team. It should also be noted that there are ongoing
debates regarding screening intervals in certain areas. These include the
frequency, modality of screening and degree of intervention for astrocytomas and
renal angiomyolipomas. This review seeks to summarise the product of the ongoing
debates, and provide evidence-based suggestions in light of the uncertainty.
PMID- 25112287
TI - Alpha-lipoic acid enhances DMSO-induced cardiomyogenic differentiation of P19
cells.
AB - Alpha-lipoic acid (alpha-LA) is a potent antioxidant that acts as an essential
cofactor in mitochondrial dehydrogenase reactions. alpha-LA has been shown to
possess anti-inflammatory and cytoprotective properties, and is used to improve
symptoms of diabetic neuropathy. However, the role of alpha-LA in stem cell
differentiation and the underlying molecular mechanisms remain unknown. In the
present study, we showed that alpha-LA significantly promoted dimethyl sulfoxide
(DMSO)-induced cardiomyogenic differentiation of mouse embryonic carcinoma P19
cells. alpha-LA dose dependently increased beating embryonic body (EB)
percentages of DMSO-differentiated P19 cells. The expressions of cardiac specific
genes TNNT2, Nkx2.5, GATA4, MEF2C, and MLC2V and cardiac isoform of troponin T
(cTnT)-positively stained cell population were significantly up-regulated by the
addition of alpha-LA. We also demonstrated that the differentiation time after EB
formation was critical for alpha-LA to take effect. Interestingly, without DMSO
treatment, alpha-LA did not stimulate the cardiomyogenic differentiation of P19
cells. Further investigation indicated that collagen synthesis-enhancing
activity, instead of the antioxidative property, plays a significant role in the
cardiomyogenic differentiation-promoting function of alpha-LA. These findings
highlight the potential use of alpha-LA for regenerative therapies in heart
diseases.
PMID- 25112286
TI - Fifteen minute consultation: managing neonatal and childhood herpes encephalitis.
AB - Herpes simplex encephalitis (HSE) is the most common single cause of viral
encephalitis in infants and children. Treated or untreated, it can be associated
with considerable morbidity and mortality, and its presentation is usually
insidious and non-specific. Prompt and careful investigation is important in
order to establish the diagnosis so that treatment can be optimised. We address
some common questions arising when diagnosing and treating presumed HSE
throughout childhood.
PMID- 25112288
TI - The influence of nitroglycerin on the proliferation of endothelial progenitor
cells from peripheral blood of patients with coronary artery disease.
AB - Endothelial progenitor cells (EPCs) are associated with vascular repairing and
progression of atherosclerotic lesion. It may lead to coronary artery disease
(CAD) if circulating EPCs lose their function. Continuous nitroglycerin (NTG)
therapy causes increased vascular oxidative stress and endothelial dysfunction.
The aim of this study was to investigate the effects of NTG on the proliferation
of human peripheral blood-derived EPCs. EPC cultures, collected from 60 CAD
patients and cultured for 7-12 days, were treated with different concentrations
of NTG (0.0, 0.3, 1.0, 2.0, 7.5, 15.0, and 20.0 mg/l) for 72 h, respectively. The
cell counts and proliferative activities of EPC; the levels of vascular
endothelial growth factor-A (VEGF-A), nitric oxide (NO) and peroxynitrite (ONOO(
)) in culture medium; and the level of reactive oxygen species (ROS) in adherent
cells were measured. Compared with control (0.0 mg/l NTG), the cell number and
proliferative activities of EPCs were increased when treated with 1.0 mg/l NTG
and reached maximum level when NTG concentration was 7.5 mg/l. However, there was
a significant reduction when treated with higher doses of NTG (>=15.0 mg/l).
Meanwhile, VEGF-A expression reached its maximal expression with 7.5 mg/l NTG,
but gradually declined by incubation with higher doses of NTG. There was a linear
relationship between NO level and NTG concentration, but no changes of ONOO(-)
and ROS levels were found when EPCs were incubated with 0.3-7.5 mg/l NTG.
However, ONOO(-) and ROS levels were significantly increased when incubated with
15 and 20 mg/l NTG. Our data demonstrated that moderate dose of NTG may stimulate
the proliferative activities of EPCs isolated from CAD patients.
PMID- 25112289
TI - Identification of biochemical association of phycobilisome with photosystems in
cyanobacterial state transition.
AB - State transition is a short-term balance mechanism of energy distribution between
photosystem II (PSII) and PSI. Although light-induced state transition in
cyanobacteria has been suggested to depend completely on the phycobilisome (PBS)
movement between PSII and PSI, the biochemical evidence has not been clearly
shown. In this study, we locked the association of PBS with PSII or PSI using
glycinebetaine when cells attain State 1 or 2 by exposure to light of blue or
green, respectively. Subsequently, the PBS-reaction centers were resolved by blue
native polyacrylamide gel electrophoresis and two-dimensional electrophoresis,
and then identified by western blot analysis. The results showed that in wild
type (WT) Synechocystis sp. strain PCC 6803, the PBS core always co-migrates with
the PSII dimer during light-induced State 1-State 2 transition, but its rod
leaves the PSII dimer in State 2 regardless of its co-migration in State 1. In
the light-induced State 2, the co-migration of PBS rod with PSI trimer was
observed in WT, but not in DeltandhB (M55), a State-2-transition-deficient
mutant. This study first provided the biochemical evidence for the association of
PBS with photosystems during cyanobacterial state transition.
PMID- 25112299
TI - Stem cells: epigenome reprogramming--of mice and men.
PMID- 25112300
TI - Biotransformation and chemotaxis of 4-chloro-2-nitrophenol by Pseudomonas sp.
JHN.
AB - Pseudomonas sp. JHN decolourized and biotransformed 4-chloro-2-nitrophenol
(4C2NP) in the presence of additional carbon source. The effect of the various
concentrations of the 4C2NP was studied on the decolourization of 4C2NP by
Pseudomonas sp. JHN. It was observed that strain JHN decolourized and
biotransformed 4C2NP up to concentration of 0.6 mM. Gas chromatography and gas
chromatography-mass spectrometry detected 5-chloro-2-methylbenzoxazole as a major
metabolite of the co-metabolism of 4C2NP. Furthermore, strain JHN exhibits
positive chemotaxis toward 4C2NP based on the drop plate and capillary assays.
This is the first report of the chemotaxis toward 4C2NP by any bacterium.
PMID- 25112301
TI - Analyzing periodic and random textured silicon thin film solar cells by Rigorous
Coupled Wave Analysis.
AB - A simple and fast method was developed to determine the quantum efficiency and
short circuit current of thin-film silicon solar cells prepared on periodically
or randomly textured surfaces. The optics was studied for microcrystalline thin
film silicon solar cells with integrated periodic and random surface textures.
Rigorous Coupled Wave Analysis (RCWA) was used to investigate the behaviour of
the solar cells. The analysis of the periodic and random textured substrates
allows for deriving optimal surface textures. Furthermore, light trapping in
periodic and randomly textured substrates will be compared.
PMID- 25112293
TI - Context-dependent control of alternative splicing by RNA-binding proteins.
AB - Sequence-specific RNA-binding proteins (RBPs) bind to pre-mRNA to control
alternative splicing, but it is not yet possible to read the 'splicing code' that
dictates splicing regulation on the basis of genome sequence. Each alternative
splicing event is controlled by multiple RBPs, the combined action of which
creates a distribution of alternatively spliced products in a given cell type. As
each cell type expresses a distinct array of RBPs, the interpretation of
regulatory information on a given RNA target is exceedingly dependent on the cell
type. RBPs also control each other's functions at many levels, including by
mutual modulation of their binding activities on specific regulatory RNA
elements. In this Review, we describe some of the emerging rules that govern the
highly context-dependent and combinatorial nature of alternative splicing
regulation.
PMID- 25112303
TI - Impact of Educational Levels and Health Literacy on Community Acetaminophen
Knowledge.
AB - Patient understanding of acetaminophen is important for its safe and appropriate
self-use. A cross-sectional survey was conducted in the San Francisco Bay Area to
determine the impact of educational level, patient health literacy score, and
other demographic characteristics on acetaminophen knowledge. A 17-item, in
person, paper-and-pen questionnaire containing questions about demographics and
acetaminophen knowledge was administered to 311 adults outside 5 local grocery
stores in varying socioeconomic communities. Knowledge assessed was whether
Tylenol-McNeil contains acetaminophen, maximum daily dose, and primary organ
affected by toxicity. Participant health literacy was evaluated using the Rapid
Estimate of Adult Literacy in Medicine-Short Form (REALM-SF) test. Of the 300 who
successfully completed the study, only 3.8% of all subjects were able to answer
all 3 acetaminophen knowledge questions correctly regardless of educational level
or health literacy score. This reaffirms that a lack of appropriate acetaminophen
knowledge remains present in the general population, and further efforts to
educate patients will be needed to prevent adverse events.
PMID- 25112302
TI - Efficacy of lidocaine in patients receiving palliative care with opioid
refractory cancer pain with a neuropathic component: study protocol for a
randomized controlled study.
AB - BACKGROUND: The management of patients suffering from opioid-refractory cancer
pain with a neuropathic component remains an important challenge for healthcare
workers. Only one retrospective study specifically reported the use of
intravenous (IV) lidocaine amongst the palliative care unit population, the study
found that there was a positive response to this therapy. These preliminary
uncontrolled results need to be confirmed by randomized controlled trials. The
primary objective of this study is to assess the analgesic efficacy of IV
lidocaine in patients in palliative care suffering from opioid-refractory cancer
pain with a neuropathic component. The secondary objectives are to assess the
tolerance of, symptomatology, and patient satisfaction with the therapeutic
approach. METHODS/DESIGN: This will be a multicenter, prospective, randomized,
placebo-controlled, double-blind, two-parallel group study. It will take place in
eight adult palliative care units across France. The main inclusion criteria are
as follows: adult patients suffering from opioid-refractory cancer pain with a
neuropathic component, and those receiving palliative care as defined by French
Society of Palliative and Support Care. Participants will be randomized (1:1
allocation ratio) to one of two treatment groups: a) lidocaine-experimental group
(intravenous lidocaine), or b) placebo-control group (intravenous saline
solution). Evaluation assessments will be taken at baseline (T0 randomization),
40 minutes (T1), 120 minutes (T2), 12 hours (T3), 24 hours (T4), 48 hours (T5),
and 14 days (T6) after baseline. The primary endpoint is change in the pain level
between T0 and T1. The secondary endpoints are: changes in the pain level between
T0 and other times, intensity of the neuropathic pain component, daily opioid
consumption, symptoms (as classified by the MD Anderson Symptom Inventory),
adverse events, and patient's satisfaction (measured using the Pain Treatment
Satisfaction Scale). A sample size of 200 individuals will be needed to obtain
90% power to detect a 25% difference in pain success at T1 between the two
groups; pain success is classified as a 30% decrease in the pain level between T0
and T1 (10% of patients lost to follow-up expected). DISCUSSION: The randomized,
double-blind, placebo-controlled design is the most appropriate design to
demonstrate the efficacy of a new experimental intervention (Evidence-Based
Medicine Working Group classification). National and international
recommendations could be updated based on the findings of this study. TRIAL
REGISTRATION: Current controlled trials NCT02137954 (registration date: 7 May
2014).
PMID- 25112305
TI - Symptomatic Overlap and Therapeutic Opportunities in Primary Headache.
AB - Headache, a nearly universal experience, remains costly, disabling, and often
suboptimally managed. The most common presentations in the United States are
migraine, tension-type headache (TTH) and "sinus" headache, but their extensive
symptomatic overlap suggests that these conditions can be approached as
variations in the same underlying pathology and managed accordingly. We use case
studies of patients with varying prior diagnoses (none, migraine, TTH, and sinus
headache), as well as a 4-question diagnostic screening tool, to illustrate how
pharmacists can use this conceptual framework to simplify identification,
management, and referral of patients with primary headache conditions of
uncertain etiology.
PMID- 25112304
TI - Evaluation of Treatment Courses When Vancomycin Is Given Every 8 Hours in Adult
Patients.
AB - BACKGROUND: Several nomograms include recommendations to give intravenous (IV)
vancomycin at 8-hour dosing intervals (Q8H). However, there is a lack of detailed
data regarding this dosing recommendation. METHODS: A retrospective chart review
of 100 patients who received 107 treatment courses of vancomycin Q8H for at least
5 days was performed. Distribution of vancomycin trough levels and rate of
nephrotoxicity were evaluated. RESULTS: Median patient age was 38 years
(interquartile range [IQR] 27-50 years), median weight was 67 kg (IQR 55-79 kg),
and median creatinine clearance was 124 mL/min (IQR 101-147 mL/min). Median
duration of Q8H dosing was 9 days (IQR 7-12 days). Within the initial 96 hours,
only 7% (7 of 104) of maximum trough concentrations were >20 mg/L (median dose 15
mg/kg [IQR 15-18 mg/kg]). After 96 hours of Q8H dosing, 34% (30 of 89) of maximum
troughs were >20 mg/L (median dose 17 mg/kg [IQR 15-20 mg/kg]), P = .0005. The
rate of nephrotoxicity was 4%. CONCLUSION: We observed an increase in the
percentage of trough levels >20 mg/L later during treatment courses of vancomycin
IV Q8H with a relatively small corresponding increase in vancomycin dose. Close
monitoring of trough levels (eg, every 3 days) with prolonged courses of
vancomycin IV Q8H is warranted.
PMID- 25112306
TI - A Comprehensive Review of Potential Warfarin-Fruit Interactions.
AB - PURPOSE: The aim of this review is to discuss possible interactions that may
occur between warfarin and fruit products. METHODS: A literature search was
conducted using the search terms: "warfarin (Coumadin(r)) and fruit interactions,
warfarin and fruit, warfarin and fruit juice, case reports and clinical trials".
RESULTS: A total of 23 citations (15 case reports and 7 controlled clinical
trials) were reviewed. The majority of cases involved cranberry products, while
pomegranate juice, avocado, grapefruit juice, mango, and papain were also
implicated in reports of suspected warfarin-fruit interactions. Cranberry juice
was also the most frequently studied fruit product. Other fruit products
evaluated with warfarin in controlled clinical trials were cranberry concentrate
and grapefruit juice. CONCLUSION: Although a number of case reports have been
published that suggest warfarin has the potential to interact with several fruit
products, it is difficult to determine their relevance, as scientific evidence is
scarce. Until further information is available, clinicians may want to encourage
patients to consume cranberry products and grapefruit juice in small to moderate
quantities and to inquire about the recent consumption of mangos, pomegranate
juice, and avocados when taking a dietary history or when assessing possible
causes for international normalized ratio (INR) instability.
PMID- 25112309
TI - Transthyretin-type cerebral amyloid angiopathy: a serious complication in post
transplant patients with familial amyloid polyneuropathy.
PMID- 25112307
TI - Brief intervention for medication-overuse headache in primary care. The BIMOH
study: a double-blind pragmatic cluster randomised parallel controlled trial.
AB - BACKGROUND: Medication-overuse headache (MOH) is common in the general
population. We investigated effectiveness of brief intervention (BI) for
achieving drug withdrawal in primary care patients with MOH. METHODS: The study
was double-blind, pragmatic and cluster-randomised controlled. A total of 25,486
patients (age 18-50) from 50 general practitioners (GPs) were screened for MOH.
GPs defined clusters and were randomised to receive BI training (23 GPs) or to
continue business as usual (BAU; 27 GPs). The Severity of Dependence Scale was
applied as a part of the BI. BI involved feedback about individual risk of MOH
and how to reduce overuse. Primary outcome measures were reduction in medication
and headache days/month 3 months after the intervention and were assessed by a
blinded clinical investigator. RESULTS: 42% responded to the postal screening
questionnaire, and 2.4% screened positive for MOH. A random selection of up to
three patients with MOH from each GP were invited (104 patients), 75 patients
were randomised and 60 patients included into the study. BI was significantly
better than BAU for the primary outcomes (p<0.001). Headache and medication days
were reduced by 7.3 and 7.9 (95% CI 3.2 to 11.3 and 3.2 to 12.5) days/month in
the BI compared with the BAU group. Chronic headache resolved in 50% of the BI
and 6% of the BAU group. CONCLUSIONS: The BI method provides GPs with a simple
and effective instrument that reduces medication-overuse and headache frequency
in patients with MOH. TRIAL REGISTRATION NUMBER: NCT01314768.
PMID- 25112308
TI - A study of up to 12 years of follow-up of Friedreich ataxia utilising four
measurement tools.
AB - OBJECTIVE: To explore the progression of Friedreich ataxia by analysing the
change in scores of four clinical measures (the Friedreich Ataxia Rating Scale
(FARS), the International Cooperative Ataxia Rating Scale (ICARS), the Functional
Independence Measure (FIM) and the Modified Barthel Index (MBI)) over a period of
up to 12 years, to ascertain the effects of clinical variables on performance of
these measures, and to determine the most sensitive rating scale for measuring
disease progression. METHODS: We measured the disease progression of up to 147
individuals against disease duration grouped into 5-year intervals. Additional
subgroups were created to study the effects of the size of the smaller FXN intron
1 GAA repeat size (GAA1) and onset age on rating scale performance. RESULTS: Both
the FARS and ICARS demonstrated greater change in the first 20 years post disease
onset than in the subsequent 20 years during which there was little change in the
mean score. While the FIM and MBI continued to deteriorate beyond 20 years post
disease onset, floor effects were noted. As measured by the FARS, individuals
with a larger GAA1 repeat were found to progress more quickly in the first 20
years of disease. CONCLUSIONS: Individuals with larger GAA1 repeat sizes and
earlier ages of disease onset were shown to deteriorate at a faster rate and were
associated with greater FARS and ICARS scores and lower FIM and MBI scores, which
are indicative of greater disease severity.
PMID- 25112310
TI - Contraceptive counselling and self-prescription of contraceptives of German
gynaecologists: results of a nationwide survey.
AB - OBJECTIVE: To evaluate the attitude toward contraceptive methods of
gynaecologists who, in Germany, are the sole prescribers of contraceptives.
METHODS: An anonymous questionnaire was sent to 9545 gynaecologists inquiring
about factors involved in their prescription of contraceptives, the
contraceptives they preferred, and those they would recommend to their daughter,
if they had one. RESULTS: The response rate of this survey was 21% (N = 2016).
The combined oral contraceptive (COC) was the most commonly prescribed method
followed by the levonorgestrel-releasing intrauterine system (LNG-IUS), the
vaginal ring, the progestin-only pill (POP), the patch, and the progestin-only
injectables. Of the respondents 51% would never prescribe the patch and 45% would
never prescribe the hormonal implant at all; 61% would choose the LNG-IUS for
themselves/for their partner; 18% would opt for a COC and 8% for the vaginal
ring. Concerning their imaginary daughter, 71% would prefer a COC, 26% the ring,
and 9% the LNG-IUS. The first counselling session lasted 13.8 +/- 4.9 min, and
the provision of information on the occasion of following visits 6.6 +/- 3.2 min.
CONCLUSION: The contraceptives most prescribed by German gynaecologists were
COCs, followed by the LNG-IUS, the vaginal ring, and POPs. The spectrum of
contraceptives preferred for personal use differed in some ways from those
prescribed to patients. Reasons for this discrepancy should be investigated.
PMID- 25112311
TI - Osteogenic differentiation of amniotic epithelial cells: synergism of pulsed
electromagnetic field and biochemical stimuli.
AB - BACKGROUND: Pulsed electromagnetic field (PEMF) is a non-invasive physical
therapy used in the treatment of fracture nonunion or delayed healing. PEMF can
facilitate the osteogenic differentiation of bone marrow mesenchymal stem cells
in vitro. Amniotic epithelial cells (AECs) have been proposed as a potential
source of stem cells for cell therapy. However, whether PEMF could modulate the
osteogenic differentiation of AECs is unknown. In the present study, the effects
of PEMF on the osteogenic differentiation of AECs were investigated. METHODS:
AECs were isolated from amniotic membrane of human placenta by trypsin digestion
and were induced by PEMF and/or osteo-induction medium. After 21 days we used
real time RT-PCR and immunocytochemistry to study the expression of osteoblast
markers. The signal transduction of osteogenesis was further investigated.
RESULTS: The PEMF stimulation, or osteo-induction medium alone could induce
osteogenic differentiation of AECs, as shown by expression of osteoblast specific
genes and proteins including alkaline phosphatase and osteocalcin. Furthermore, a
combination of PEMF and osteo-induction medium had synergy effects on osteogenic
differentiation. In our study, the gene expression of BMP-2, Runx2, beta-catenin,
Nrf2, Keap1 and integrinbeta1 were up-regulated in the osteogenic differentiation
of AECs induced by PEMF and/or osteo-induction medium. CONCLUSIONS: Combined
application of PEMF and osteo-induction medium is synergistic for the osteogenic
differentiation of AECs. It might be a novel approach in the bone regenerative
medicine.
PMID- 25112312
TI - Protective immunity of 56-kDa type-specific antigen of Orientia tsutsugamushi
causing scrub typhus.
AB - Scrub typhus, caused by infection with Orientia tsutsugamushi, is a mite-borne
zoonotic disease endemic to the Asian-Pacific region. In Korea, the incidence of
this disease has increased with climate changes, and over 10,000 cases of
infection were reported in 2013. Although this infection is treatable with
antibiotics such as doxycycline and azithromycin, an effective prophylactic
vaccine against O. tsutsugamushi would be more desirable for preventing scrub
typhus in endemic areas. In this study, we investigated the 56-kDa type-specific
antigen (TSA56), which is a major outer membrane protein of O. tsutsugamushi, as
a vaccine candidate. Intranasal immunization of recombinant TSA56 (rec56) induced
a higher level of TSA56- specific IgG than that induced by intramuscular
immunization of tsa56-expressing DNA (p56). Both types of immunization induced a
cell-mediated immune response to TSA56, as demonstrated by the splenic cell
proliferation assay. Mice immunized with p56, followed by rec56 plus heat-labile
enterotoxin B subunit from E. coli, had a stronger protection from a homologous
challenge with the O. tsutsugamushi Boryong strain than with other combinations.
Our preliminary results suggest that an effective human vaccine for scrub typhus
can include either recombinant TSA56 protein or tsa56-expressing DNA, and provide
the basis for further studies to optimize vaccine performance using additional
antigens or different adjuvants.
PMID- 25112314
TI - Cloning and characterization of a multidomain GH10 xylanase from Paenibacillus
sp. DG-22.
AB - The xynC gene, which encodes high molecular weight xylanase from Paenibacillus
sp. DG-22, was cloned and expressed in Escherichia coli, and its nucleotide
sequence was determined. The xynC gene comprised a 4,419 bp open reading frame
encoding 1,472 amino acid residues, including a 27 amino acid signal sequence.
Sequence analysis indicated that XynC is a multidomain enzyme composed of two
family 4_9 carbohydrate-binding modules (CBMs), a catalytic domain of family 10
glycosyl hydrolases, a family 9 CBM, and three S-layer homologous domains.
Recombinant XynC was purified to homogeneity by heat treatment, followed by
Avicel affinity chromatography. SDS-PAGE and zymogram analysis of the purified
enzyme identified three active truncated xylanase species. Protein sequencing of
these truncated proteins showed that all had identical N-terminal sequences. In
the protein characterization, recombinant XynC exhibited optimal activity at pH
6.5 and 65 degrees C and remained stable at neutral to alkaline pH (pH 6.0
10.0). The xylanase activity of recombinant XynC was strongly inhibited by 1 mM
Cu(2+) and Hg(2+), whereas it was noticeably enhanced by 10 mM dithiothreitol.
The enzyme exhibited strong activity towards xylans, including beechwood xylan
and arabinoxylan, whereas it showed no cellulase activity. The hydrolyzed product
patterns of birchwood xylan and xylooligosaccharides by thin-layer chromatography
confirmed XynC as an endoxylanase.
PMID- 25112313
TI - Quorum quenching bacteria isolated from the sludge of a wastewater treatment
plant and their application for controlling biofilm formation.
AB - Bacteria recognize changes in their population density by sensing the
concentration of signal molecules, N-acyl-homoserine lactones (AHLs). AHL
mediated quorum sensing (QS) plays a key role in biofilm formation, so the
interference of QS, referred to as quorum quenching (QQ), has received a great
deal of attention. A QQ strategy can be applied to membrane bioreactors (MBRs)
for advanced wastewater treatment to control biofouling. To isolate QQ bacteria
that can inhibit biofilm formation, we isolated diverse AHL-degrading bacteria
from a laboratory-scale MBR and sludge from real wastewater treatment plants. A
total of 225 AHLdegrading bacteria were isolated from the sludge sample by
enrichment culture. To identify the enzyme responsible for AHL degradation in QQ
bacteria, AHL-degrading activities were analyzed using cell-free lysate, culture
supernatant, and whole cells. Afipia sp. and Acinetobacter sp. strains produced
the intracellular QQ enzyme, whereas Pseudomonas sp. and Micrococcus sp. produced
the extracellular QQ enzyme that was most likely to produce AHLacylase. AHL
degrading activity was observed in whole-cell assay with the Microbacterium sp.
and Rhodococcus sp. strains. There has been no report for AHL-degrading
capability in the case of Streptococcus sp. and Afipia sp. strains. Finally,
inhibition of biofilm formation by isolated QQ bacteria or enzymes was observed
on glass slides and 96-well microtiter plates using crystal violet staining. QQ
strains or enzymes not only inhibited initial biofilm development but also
reduced established biofilms.
PMID- 25112315
TI - Reverse micellar extraction of fungal glucoamylase produced in solid-state
fermentation culture.
AB - Partial purification of glucoamylase from solid-state fermentation culture was,
firstly, investigated by reverse micellar extraction (RME). To avoid back
extraction problems, the glucoamylase was kept in the original aqueous phase,
while the other undesired proteins/ enzymes were moved to the reverse micellar
organic phase. The individual and interaction effects of main factors (i.e., pH
and NaCl concentration in the aqueous phase, and concentration of sodium bis-2
ethyl-hexyl-sulfosuccinate (AOT) in the organic phase) were studied using
response surface methodology. The optimum conditions for the maximum recovery of
the enzyme were pH 2.75, 100 mM NaCl, and 200 mM AOT. Furthermore, the optimum
organic to aqueous volume ratio (Vorg/Vaq) and appropriate number of sequential
extraction stages were 2 and 3, respectively. Finally, 60% of the undesired
enzymes including proteases and xylanases were removed from the aqueous phase,
while 140% of glucoamylase activity was recovered in the aqueous phase and the
purification factor of glucoamylase was found to be 3.0-fold.
PMID- 25112316
TI - Crystal structure of (S)-3-hydroxybutyryl-CoA dehydrogenase from Clostridium
butyricum and its mutations that enhance reaction kinetics.
AB - 3-Hydroxybutyryl-CoA dehydrogenase is an enzyme that catalyzes the second step in
the biosynthesis of n-butanol from acetyl-CoA, in which acetoacetyl-CoA is
reduced to 3-hydroxybutyryl-CoA. To understand the molecular mechanisms of n
butanol biosynthesis, we determined the crystal structure of 3-hydroxybutyryl-CoA
dehydrogenase from Clostridium butyricum (CbHBD). The monomer structure of CbHBD
exhibits a two-domain topology, with N- and C-terminal domains, and the
dimerization of the enzyme was mostly constituted at the C-terminal domain. The
mode of cofactor binding to CbHBD was elucidated by determining the crystal
structure of the enzyme in complex with NAD(+). We also determined the enzyme's
structure in complex with its acetoacetyl-CoA substrate, revealing that the
adenosine diphosphate moiety was not highly stabilized compared with the
remainder of the acetoacetyl-CoA molecule. Using this structural information, we
performed a series of sitedirected mutagenesis experiments on the enzyme, such as
changing residues located near the substrate-binding site, and finally developed
a highly efficient CbHBD K50A/K54A/L232Y triple mutant enzyme that exhibited
approximately 5-fold higher enzyme activity than did the wild type. The increased
enzyme activity of the mutant was confirmed by enzyme kinetic measurements. The
highly efficient mutant enzyme should be useful for increasing the production
rate of n-butanol.
PMID- 25112317
TI - Improvement of Wuyiencin biosynthesis in Streptomyces wuyiensis CK-15 by
identification of a key regulator, WysR.
AB - Wuyiencin is produced by Streptomyces ahygroscopicus var. wuyiensis CK-15 and is
widely used as an antifungal agent in agriculture. Analysis of wuyiencin
biosynthetic gene clusters reveals wysR, a member of the LAL-family of
transcriptional regulatory genes. WysR consists of an Nterminal PAS domain and a
LuxR family C-terminal helix-turn-helix motif. However, the roles of wysR in
wuyiencin biosynthesis are largely unknown. In this study, we showed that
inactivation of wysR resulted in the complete loss of wuyiencin production, which
could be restored by complementation with a single copy of wysR. Furthermore, we
successfully increased wuyiencin production to a significantly higher level by
overexpression of wysR in S. wuyiensis CK-15. Quantitative real-time RT-PCR
analysis showed that WysR regulates wuyiencin biosynthesis by modulating other
putative regulatory genes. Thus, WysR was identified as an activator of wuyiencin
biosynthesis, and overexpression of wysR gene proved to be an effective strategy
for improving wuyiencin production.
PMID- 25112318
TI - Oral administration of Lactobacillus plantarum HY7714 protects hairless mouse
against ultraviolet B-induced photoaging.
AB - Ultraviolet (UV) irradiation alters multiple molecular pathways in the skin,
thereby inducing skin damage, including photoaging. In recent years, probiotics
have gained interest due to their beneficial effects on skin health, such as
inhibiting atopic dermatitis and improving skin immunity or inflammation.
However, little is known about the effects of probiotics on UVBinduced
photoaging. In this study, we evaluated the effect of Lactobacillus plantarum
HY7714 against UVB-induced photoaging in human dermal fibroblasts and hairless
mice. The results showed that L. plantarum HY7714 treatment effectively rescued
UVB-reduced procollagen expression through the inhibition of UVB-induced matrix
metalloproteinase (MMP)-1 expression in human dermal fibroblasts. Data from a
western blot showed that L. plantarum HY7714 inhibited the phosphorylation of Jun
N-terminal kinase, thereby suppressing the UVB-induced phosphorylation and
expression of c-Jun. Oral administration of L. plantarum HY7714 clearly inhibited
the number, depth, and area of wrinkles in hairless mouse skin. Histological data
showed that L. plantarum HY7714 significantly inhibited UVB-induced epidermal
thickness in mice. Western blot and zymography data also revealed that L.
plantarum HY7714 effectively inhibited MMP-13 expression as well as MMP-2 and -9
activities in dermal tissue. Collectively, these results provide further insight
regarding the skin biological actions of L. plantarum HY7714, a potential skin
anti-photoaging agent.
PMID- 25112319
TI - Insect cell surface expression of hemagglutinin (HA) of Egyptian H5N1 avian
influenza virus under transcriptional control of whispovirus immediate early-1
promoter.
AB - In the present study, whispovirus immediate early 1 promoter (ie-1) was used to
initiate surface expression of the hemagglutinin (HA) protein of Egyptian H5N1
avian influenza virus (AIV) by using the baculovirus expression vector system.
The HA gene and whispovirus ie-1 promoter sequence were synthesized as a fused
expression cassette (ie1-HA) and successfully cloned into the pFastBac-1 transfer
vector. The recombinant vector was transformed into DH10Bac competent cells, and
the recombinant bacmid was generated via site-specific transposition. The
recombinant bacmid was used for transfection of Spodoptera frugiperda (Sf-9)
insect cells to construct the recombinant baculovirus and to induce expression of
the HA protein of H5N1 AIV. The recombinant glycoprotein expressed in Sf-9 cells
showed hemadsorption activity. Hemagglutination activity was also detected in
both extra- and intracellular recombinant HAs. Both the HA and hemadsorption
activities were inhibited by reference polyclonal anti-H5 sera. Significant
expression of the recombinant protein was observed on the surface of infected
insect cells by using immunofluorescence. SDS-PAGE analysis of the expressed
protein revealed the presence of a visually distinguishable band of ~63 kDa in
size, which was absent in the non-infected cell control. Western blot analysis
confirmed that the distinct 63 kDa band corresponded to the recombinant HA
glycoprotein of H5N1 AIV. This study reports the successful expression of the HA
protein of H5N1 AIV. The expressed protein was displayed on the plasma membrane
of infected insect cells under the control of whispovirus ie-1 promoter by using
the baculovirus expression vector system.
PMID- 25112320
TI - Higher biomass productivity of microalgae in an attached growth system, using
wastewater.
AB - Although most algae cultivation systems are operated in suspended culture, an
attached growth system can offer several advantages over suspended systems. Algal
cultivation becomes light-limited as the microalgal concentration increases in
the suspended system; on the other hand, sunlight penetrates deeper and stronger
in attached systems owing to the more transparent water. Such higher availability
of sunlight makes it possible to operate a raceway pond deeper than usual,
resulting in a higher areal productivity. The attached system achieved 2.8-times
higher biomass productivity and total lipid productivity of 9.1 g m(-2) day(-1)
and 1.9 g m(-2) day(-1), respectively, than the suspended system. Biomass
productivity can be further increased by optimization of the culture conditions.
Moreover, algal biomass harvesting and dewatering were made simpler and cheaper
in attached systems, because mesh-type substrates with attached microalgae were
easily removed from the culture and the remaining treated wastewater could be
discharged directly. When the algal biomass was dewatered using natural sunlight,
the palmitic acid (C16:0) content increased by 16% compared with the freeze
drying method. There was no great difference in other fatty acid composition.
Therefore, the attached system for algal cultivation is a promising cultivation
system for mass biodiesel production.
PMID- 25112321
TI - Different immune regulatory potential of Lactobacillus plantarum and
Lactobacillus sakei isolated from Kimchi.
AB - It is known that lactic acid bacteria (LAB) have many beneficial health effects,
including antioxidative activity and immune regulation. In this study, the immune
regulatory effects of Lactobacillus sakei and Lactobacillus plantarum, which are
found in different types of kimchi, were evaluated. L. sakei and its lipoteichoic
acid (LTA) have greater immune stimulating potential in IL-12, IFN-gamma, and TNF
alpha production as compared with L. plantarum in an in vitro condition. On the
other hand, L. plantarum is assumed to repress the Th1 immune response in murine
experiments. After being injected with LPS, L. plantarum-fed mice maintained a
healthier state, and the level of TNF-alpha in their blood was lower than in
other bacterial strainfed mice and in the LPS-only control mice. Additionally, IL
12 production was significantly decreased and the production of IL-4 was greatly
increased in the splenocytes from L. plantarum-fed mice. Further experiments
revealed that the pre-injection of purified LTA from L. plantarum (pLTA), L.
sakei (sLTA), and S. aureus (aLTA) decreased TNF-alpha and IL-4 production in LPS
injected mice. Mouse IL-12, however, was significantly increased by aLTA pre
injection. In conclusion, the L. sakei and L. plantarum strains have immune
regulation effects, but the effects differ in cytokine production and the
regulatory effects of the Th1/Th2 immune response.
PMID- 25112323
TI - Systematic revision of the family Hoplitomerycidae Leinders, 1984 (Artiodactyla:
Cervoidea), with the description of a new genus and four new species.
AB - Six species of the cervoid genus Hoplitomeryx are currently recognized from the
Late Miocene sites of Gargano and Scontrone, in Italy: H. matthei Leinders, 1984,
H. apruthiensis Mazza & Rustioni, 2011, H. apulicus Mazza & Rustioni, 2011, H.
falcidens Mazza & Rustioni, 2011, H. magnus Mazza & Rustioni, 2011, and H.
minutus Mazza & Rustioni, 2011. These species are interpreted as members of an
anagenetic series in these two localities, which are considered as part of the
same bioprovince but with different geological ages. Comparative analysis of
postcranial, dental, and cranial material from Hoplitomerycidae resulted in the
reinterpretation of this current taxonomic arrangement. Two distinct genera can
be distinguished. The new genus Scontromeryx is restricted to Scontrone (Early
Tortonian) and is characterised by the presence of second upper and lower
premolars and the absence of a nasal (median) horn. Hoplitomeryx is restricted to
Gargano (Middle and/or Late Tortonian), and is characterized by the loss of the
second premolar and presence of a nasal horn. Both genera are characterized by
orbital appendages in some species, but the morphology of these appendages
differs between the genera. Six species can be recognized for Scontromeryx gen.
n.: S. minutus (type species), S. falcidens, S. apulicus, S. apruthiensis, S.
magnus (new combinations) and the newly described S. mazzai sp. n.. Hoplitomeryx
is represented by the H. matthei (type species) and 3 newly described species H.
devosi sp. n., H. macpheei sp. n. and H. kriegsmani sp. n.. These two
multispecies assemblages are best explained as independent adaptive radiations
with the two genera as sister taxa. There is no evidence that the two localities
were connected during the Late Miocene.
PMID- 25112322
TI - Molecular and biochemical characteristics of beta-propeller phytase from marine
Pseudomonas sp. BS10-3 and its potential application for animal feed additives.
AB - Phytate is an antinutritional factor that impacts the bioavailability of
essential minerals such as Ca(2+), Mg(2+), Mn(2+), Zn(2+), and Fe(2+) by forming
insoluble mineral-phytate salts. These insoluble mineral-phytate salts are
hydrolyzed rarely by monogastric animals, because they lack the hydrolyzing
phytases and thus excrete the majority of them. The beta-propeller phytases
(BPPs) hydrolyze these insoluble mineral-phytate salts efficiently. In this
study, we cloned a novel BPP gene from a marine Pseudomonas sp. This Pseudomonas
BPP gene (PsBPP) had low sequence identity with other known phytases and
contained an extra internal repeat domain (residues 24-279) and a typical BPP
domain (residues 280-634) at the C-terminus. Structurebased sequence alignment
suggested that the N-terminal repeat domain did not possess the active-site
residues, whereas the C-terminal BPP domain contained multiple calcium-binding
sites, which provide a favorable electrostatic environment for substrate binding
and catalytic activity. Thus, we overexpressed the BPP domain from Pseudomonas
sp. to potentially hydrolyze insoluble mineral-phytate salts. Purified
recombinant PsBPP required Ca(2+) or Fe(2+) for phytase activity, indicating that
PsBPP hydrolyzes insoluble Fe(2+)-phytate or Ca2+-phytate salts. The optimal
temperature and pH for the hydrolysis of Ca(2+)-phytate by PsBPP were 50 degrees
C and 6.0, respectively. Biochemical and kinetic studies clearly showed that
PsBPP efficiently hydrolyzed Ca(2+)-phytate salts and yielded myo-inositol 2,4,6
trisphosphate and three phosphate groups as final products. Finally, we showed
that PsBPP was highly effective for hydrolyzing rice bran with high phytate
content. Taken together, our results suggest that PsBPP has great potential in
the animal feed industry for reducing phytates.
PMID- 25112324
TI - Review and phylogeny of the geniculata group, genus Chinavia (Heteroptera:
Pentatomidae), with notes on biogeography and morphological evolution.
AB - Chinavia is one of the most diverse genera of Pentatomidae, comprising 80 species
distributed in the Afrotropical, Neartic and Neotropical regions. Some groups of
species have been proposed in the literature based on morphological similarities
or phylogenetic analyses. The geniculata group was proposed to include C.
geniculata, C. gravis and C. nigritarsis. However, eleven other species of
Chinavia share somatic and genital characteristics with C. geniculata, C. gravis
and C. nigritarsis, which allows hypothesizing the monophyly among these 14
species. In spite of the recent contributions to aspects of biology, immature
stages and species catalogs in Chinavia, the definition of monophyletic groups
within the genus and the establishment of boundaries among its species are
essential to understand its diversity and to test hypotheses on biogeography and
evolutionary biology. In this study we review the taxonomy of the geniculata
group, test its monophyly and propose a phylogenetic hypothesis for the group. We
discuss the phylogenetic relationships from a geographical perspective, and
provide insights about morphological evolution.
PMID- 25112325
TI - Review of the species of the genus Serrapinnus Malabarba, 1998 (Teleostei:
Characidae: Cheirodontinae) from the rio Tocantins-Araguaia basin, with
description of three new species.
AB - Species of the genus Serrapinnus from the rio Tocantins-Araguaia basin are
revised and three new species are described. Serrapinnus aster new species is
diagnosed by the presence of scimitar-shaped ventral procurrent caudal-fin rays
of mature males forming a semicircle and by the presence of 7-9 cusps on the
premaxillary teeth; S. lucindai new species is distinguished from its congeners
by the presence of a higher number of ventral procurrent caudal-fin rays (17 to
19); and S. tocantinensis new species differs from the remaining species of the
genus by the elongation of the unbranched dorsal and pelvic-fin rays into
filaments in mature males. Serrapinnus sterbai is recognized as broadly
distributed in the Tocantins-Araguaia basin and is redescribed based on specimens
from across its entire distribution. A key for the cheirodontines occurring in
the Atlantic drainages of northeastern Brazil, from the rio Tocantins-Araguaia to
the rio Paraguacu is provided.
PMID- 25112326
TI - Vietnamese Issidae (Hemiptera, Fulgoroidea): new taxa, new records and new
distribution data.
AB - An updated list of Issidae known from Vietnam is provided. Two new species, one
from the genus Darwallia Gnezdilov, 2010, and another one from a new genus are
described from the Hon Ba massif in Central Vietnam. A key to species of the
genus Darwallia is provided. Gelastyrella hainanensis Ran et Liang, 2006 is
placed in synonymy under Thabena litaoensis Yang, 1994. This last taxon and the
genus Gergithoides Schumacher, 1915 are recorded for the first time for
Vietnamese fauna. New records in Vietnam are given for Tetrica philo Fennah, 1978
and Gergithus iguchii Matsumura, 1916.
PMID- 25112327
TI - Afrotropical flower flies (Diptera: Syrphidae). A new genus and species from
Kenya, with a review of the melanostomine group of genera.
AB - A new genus and species of flower flies (Diptera: Syrphidae: Syrphinae: Syrphini)
are described from central Africa (Kenya & Uganda), Afrostoma quadripunctatum. A
key to the Afrotropical genera of the subfamily Syrphinae is given. A review of
the melanostomine [Bacchini] genera and subgenera is provided along with a key to
them. Phylogenetic placement of Afrostoma is included based on mitochondrial
cytochrome c oxidase subunit I (COI) data.
PMID- 25112328
TI - Leeonychiurus, a new genus from East Asia (Collembola: Onychiuridae:
Onychiurini).
AB - A new genus of Onychiurini including five species is described from East Asia.
Leeonychiurus gen. nov. differs in its antennal III sensory organ with granulated
sensory clubs and 11 chaetae in the distal whorl of tibiotarsi. The main
diagnostic characters of the genera from the tribe Onychiurini and the five
species from the new genus are summarized. A new species, Leeonychiurus
fusongensis sp. nov., is reported from northeast China and it can be easily
distinguished from other species of the genus by the number of dorsal and ventral
pseudocelli. The known Korean species L. polychaetosus is redescribed by the
examination of the type materials.
PMID- 25112329
TI - A new species of Endecous Saussure, 1878 (Orthoptera, Gryllidae) from northeast
Brazil with the first X1X20 chromosomal sex system in Gryllidae.
AB - In this paper we describe a new species of Luzarinae cricket collected from the
cave "Gruta de Ubajara, municipality of Ubajara, State of Ceara, Brazil,
highlighting phallic sclerites morphology and chromosome complement as diagnostic
characters. We presented meiotic and mitotic characterization in order to define
the karyotype with 2n = 12 + X1X2?/12 + X1X1X2X2?. This represents the first
record of X1X20 chromosomal sex system in Gryllidae.
PMID- 25112330
TI - A new species of the genus Aspidiotes Schoenherr, 1847 (Coleoptera:
Curculionidae: Tanymecini) from Middle Anatolia (Turkey).
AB - A new species of Aspidiotes Schoenherr, 1847 (Curculionidae: Tanymecini) from
Turkey is described and illustrated. Aspidiotes (Phaenognathus) candani sp. nov.
is closely related to A. anatolicus (Colonnelli) but can be separated by eye
shape, form of pronotum, form of setae on disc of elytra, surface morphology of
scales, structure of aedeagus (in dorsal view) and form of spermatheca.
PMID- 25112331
TI - Paracriodion Fragoso (Coleoptera: Cerambycidae: Cerambycinae): redefinition, with
description of a new species from Bolivia.
AB - The genus Paracriodion Fragoso, 1982, is redefined. A new species from Bolivia,
P. morrisi sp. nov., is described. A key for Paracriodion species is included and
new distributional data for P. romani (Aurivillius, 1926) are given.
PMID- 25112332
TI - The genus Anahita from Wuyi Mountains, Fujian, China, with description of one new
species (Araneae: Ctenidae).
PMID- 25112333
TI - An updated checklist of Nepticulidae (Lepidoptera) of the Crimea, Sub
Mediterranean SE Europe.
AB - This updated checklist is intended to be a collaborative effort by a team of
taxonomists to present a hitherto little known diversity of the Nepticulidae of
the Crimea. A total of 64 species of Nepticulidae are listed. The following 26
species are recorded for the first time from the Crimea: Stigmella confusella
(Wood & Walsingham, 1894), S. tiliae (Frey, 1856), S. microtheriella (Stainton,
1854), S. alnetella (Stainton, 1854), S. glutinosae (Stainton, 1858), S.
desperatella (Frey, 1856), S. torminalis (Wood, 1890), S. crataegella (Klimesch,
1936), S. hahniella (Worz, 1937), S. catharticella (Stainton, 1853), S. malella
(Stainton, 1854), S. rhamnella (Herrich-Schaffter, 1860), S. ulmivora (Fologne,
1860), S. trimaculella (Haworth, 1828), S. obliquella (Heinemann, 1862), S.
tityrella (Stainton, 1854), S. carpinella (Heinemann, 1862), S. lemniscella
(Zeller, 1839), S. plagicolella (Stainton, 1854), S. samiatella (Zeller, 1939),
Bohemannia pulverosella (Stainton, 1849), Ectoedemia mahalebella (Klimesch,
1936), Fomoria septembrella (Stainton, 1849), Trifurcula silviae van Nieukerken,
1990, T. macedonica Z. Lastuvka & A. Lastuvka, 1998, T. eurema (Tutt, 1899). One
species, Ectoedemia spinosella (Joannis, 1908), is excluded here from the list of
the Nepticulidae of the Crimea. Thirty-nine selected species are illustrated with
photographs of the leaf-mines, and forty-five species with photographs of
genitalia.
PMID- 25112334
TI - Review of the Stenothemus harmandi species-group (Coleoptera, Cantharidae), with
description of six new species from China.
AB - The diagnosis of the Stenothemus harmandi species-group is summarized, and all
species are reviewed and keyed. S. harmandi (Bourgeois, 1902) is redescribed and
six new species are described, S. fugongensis sp. nov. (CHINA: Yunnan), S.
distortirudis sp. nov. (CHINA: Xizang), S. parallelus sp. nov. (CHINA: Xizang),
S. septimus sp. nov. (CHINA: Xizang), S. leishanensis sp. nov. (CHINA: Guizhou)
and S. laticollis sp. nov. (CHINA: Xizang). Each species treatment is provided
with photos of habitus of male and abdominal sternite VIII of female, and
illustrations of aedeagus. Additionally, S. subnitidus Svihla, 2005, S.
holosericus Svihla, 2005 and S. orbiculatus Svihla, 2005 are provided with
supplementary descriptions and photos of abdominal sternites VIII of females.
Distribution maps are provided for each species of the S. harmandi species-group.
PMID- 25112335
TI - Revision of the brachiopod genus Amphithyris (Rhynchonelliformea: Platidiidae)
with descriptions of two new species.
AB - The recent brachiopod genus Amphithyris Thomson belongs to the family Platidiidae
and to date comprises five species, A. seminula (Philippi, 1836), A. buckmani
Thomson, 1918, A. hallettensis Foster, 1974, A. richardsonae Campbell & Fleming,
1981 and A. parva MacKinnon, Hiller, Long & Marshall, 2008. Like other platidiid
genera, Amphithyris has a worldwide distribution, but is mainly found in the
southern hemisphere, with the exception of A. seminula which occurs in the
Mediterranean Sea. This study is the first revision of the genus Amphithyris. We
describe two new species, A. cavernicola n. sp. from the Queensland Plateau,
Coral Sea, Australia and A. comitodentis n. sp. from deep waters east of the
South Island, New Zealand. A. cavernicola n. sp. represents the first record of
the genus from Australian waters, whereas A. comitodentis n. sp. is the first
species in the genus recorded from the deep sea. Additionally, we identified the
type material of A. seminula in the brachiopod collection of the Museum fur
Naturkunde, Berlin and designated a lectotype for this species. Despite their
simple shell morphology and few diagnostic features, we were able to clearly
discriminate the (now) seven species by morphological (shell) characters such as
absence/presence of a median septum, absence/presence of capillae, shell
convexity and/or combinations of these. On the basis of all known records, the
present distribution of Amphithyris spp. and a Cretaceous origin of the genus is
discussed.
PMID- 25112336
TI - The world's biogeographical regions revisited: global patterns of endemism in
Tipulidae (Diptera).
AB - This paper explores the distributional data of 4,224 Tipulidae (Insecta: Diptera)
species to search for endemism patterns in a worldwide scale and to test the
extent to which the global patterns of endemism of the group fit into previously
proposed regionalization schemes, particularly Wallace's system and recent
revisions of it. Large scale areas of endemism are assessed using the grid-based
method implemented in VNDM. VNDM depends on the prior definition of the grid size
for analysis, but a criterion for choosing beforehand a particular grid size is
not clear. The same holds for the choice of the level of similarity in species
composition selected for the calculation of consensus areas. In our study, we
developed a methodological approach that helped defining objective criteria for
choosing suitable values for these critical variables. Large-scale areas of
endemism around the globe are identified and ranked according to endemicity
levels: 1--West Palaearctic, 2--Nearctic, 3--East Palaearctic-Oriental, 4--West
North America, 5--Australia, 6--Neotropical, 7--Sub-Saharan Africa, 8-
Palaearctic, and 9--Middle East. Our main conclusion is that there are still some
limitations in applying biogeographical classifications proposed mostly on the
basis of vertebrate distribution to other taxonomic groups, such as the
Tipulidae. While there is a general congruence of the broad-scale areas of
endemism of tipulids with previously proposed regionalization schemes, for some
areas, the sharpness of boundaries between traditional regions is not so acute,
due to a great level of overlap of part of its biotic elements.
PMID- 25112338
TI - A new species of freshwater crab of the genus Microthelphusa Pretzmann, 1968
(Crustacea: Brachyura: Pseudothelphusidae) from the Amazon region of Guyana.
AB - A new species of freshwater crab, Microthelphusa furcifer, is described and
illustrated from the Potaro-Siparuni Kuribrong River in the Guyana Shield (Amazon
region of Guyana). The new species can be easily separated from its congeners by
the morphology of the first gonopod. The first gonopod of Microthelphusa meansi
Cumberlidge, 2007, is illustrated to clarify some aspects of its morphology.
PMID- 25112337
TI - Redescription and distribution of the rare flower chafer, Periphanesthes aurora
(Motschulsky, 1858) (Coleoptera: Scarabaeidae: Cetoniinae).
AB - This paper includes a detailed redescription of the monotypic genus
Periphanesthes Kraatz, 1880 (Coleoptera: Scarabaeidae: Cetoniinae) and its type
species, Periphanesthes aurora (Motschulsky, 1858), based on the lectotype
(designated within) and additional specimens. Illustrations of external features
and parameres are also provided. The distribution of P. aurora is studied, and
its new distribution records are mapped. Bonsiella Ruter, 1965 is confirmed as a
junior synonym of Periphanesthes Kraatz, 1880.
PMID- 25112339
TI - One new species in the cockroach genus Jacobsonina Hebard 1929 (Blattodea,
Ectobiidae, Blattellinae) from Mainland China.
AB - One new species of Jacobsonina Hebard from China is described and illustrated:
Jacobsonina erebis sp. nov.. A key to all known species in this genus, except for
J. lugubris (Brunner von Wattenwyl, 1893), based on males, is provided.
PMID- 25112340
TI - Re-description of the gudgeon species Saurogobio gracilicaudatus Yao & Yang in
Luo, Yue & Chen, 1977 (Teleostei: Cyprinidae) from the Chang-Jiang basin, South
China, with a note on its generic classification.
AB - Saurogobio gracilicaudatus, originally described from the middle Yangtze River
(Chang-Jiang in Chinese) basin at Yichang and Guanghua (now Laohekou), Hubei
Province, South China, is here re-described, with particular concern for
oromandibular structures in the mouth. It is uniquely distinguishable from all
other species of Saurogobio in having a rostral cap with a slightly crenulated
median portion, lips covered with brush-like, conical papillae, and a lower lip
with a small, smooth and protruded central pad anteriorly free and posteriorly
confluent with lateral lobes. The generic classification of this species is also
discussed on the basis of oromandibular structures, which are of taxonomic
importance in generic classification of gudgeons.
PMID- 25112341
TI - A new minute pirate bug of the genus Scoloposcelis (Hemiptera: Heteroptera:
Anthocoridae) from West Malaysia.
AB - Scoloposcelis seidaii sp. nov. is described from the Malay Peninsula based on a
single specimen collected under the bark of a decaying tree. This discovery
represents the first distribution record of the genus Scoloposcelis from
Malaysia. Habitus photographs and diagnosis of S. parallela (Motschulsky, 1863)
are provided for comparison with S. seidaii.
PMID- 25112342
TI - Cladocroce caelum sp. nov. from the Brazilian coast; first record of the genus in
the South Atlantic.
PMID- 25112343
TI - On cockroaches of the subfamily Epilamprinae (Dictyoptera: Blaberidae) from South
India and Sri Lanka, with descriptions of new taxa.
AB - The new genus Indoapterolampra, gen. nov. and two new species (I. rugosiuscula
sp. nov. and Morphna lucida sp. nov.) are described. Rhabdoblatta praecipua
(Walker, 1868) is removed from the synonymy with 'Polyzosteria' terranea Walker,
1868. The latter species is considered Epilamprinae gen. sp. The lectotype of
Phoraspis (Thorax) porcellana Saussure, 1862 is designated. A key for the genera
of Epilamprinae from South India and Sri Lanka is provided. Detailed
morphological descriptions of the studied taxa are given. The structure of the
male genitalia of I. rugosiuscula sp. nov., M. lucida sp. nov., M. plana (Brunner
von Wattenwyl, 1865), M. decolyi (Bolivar, 1897) and R. praecipua and that of the
female genital complex of M. decolyi, P. (T.) porcellana and Phlebonotus anomalus
(Saussure, 1863) are described for the first time. Some aspects of the cockroach
evolution are briefly discussed.
PMID- 25112344
TI - An annotated checklist of Lithobiomorpha of China.
AB - The lithobiomorph centipede fauna of China is listed here based on literature
data. A total of 68 species in 15 genera/subgenera in 2 families, Henicopidae and
Lithobiidae, has been recorded from China. Three genera and forty-four species
are known only from China, including the monotypic genera Pterygotergum and
Hedinobius. The original descriptions of 16 nominal species were based on
specimens of single sex only and 13 nominal species of Lithobius have never been
allocated to a subgenus. Lithobius (Lithobius) zhui Pei, Ma, Shi, Wu & Gai, 2011
is moved to subgenus Lithobius (Ezembius). Distribution data for each species is
provided here to promote further studies on the Lithobiomorpha fauna of China.
PMID- 25112345
TI - Rajella paucispinosa n. sp., a new deep-water skate (Elasmobranchii, Rajidae)
from the western Indian Ocean off South Mozambique, and a revised generic
diagnosis.
AB - A new species of the widely in temperate and tropical latitudes distributed skate
genus Rajella is described based on an almost adult male specimen from the
western Indian Ocean off South Mozambique. The holotype of R. paucispinosa n. sp.
was caught during cruise 17 of RV 'Vityaz' along the deep western Indian Ocean in
1988/89. It is the northernmost record of a Rajella specimen in the western
Indian Ocean. The new species is the 18th valid species of the genus and the
fifth species in the western Indian Ocean. It differs from its congeners in the
small maximal total length of about 50 cm and only few thorns on the dorsal
surface. The new species has only two thorns on each orbit, one nuchal thorn, one
right scapular thorn (left one not detectable, abraded), and one median row of
tail thorns. Other species of Rajella typically have half rings of thorns on
orbital rims, a triangle of thorns on nape-shoulder region, and at least three
rows of tail thorns. Another conspicuous feature of the new species is the almost
completely white dorsal and ventral coloration.
PMID- 25112347
TI - Fourteen new generic and ten new specific synonymies in Pholcidae (Araneae), and
transfer of Mystes Bristowe to Filistatidae.
AB - Between 1998 and 2011, the Venezuelan arachnologist Manuel Angel Gonzalez-Sponga
(GS) published a series of taxonomic papers devoted to the Pholcidae of
Venezuela. Of his 22 new genera, 20 were monotypic when described, suggesting a
high percentage of synonyms. We studied his descriptions and as far as accessible
his type specimens and propose the following new generic synonymies: Autana GS,
2011 = Mesabolivar GS, 1998; Ayomania GS, 2005 and Venezuela Kocak & Kemal, 2008
(new replacement names for Falconia GS, 2003) = Mecolaesthus Simon, 1893;
Carbonaria GS, 2009 = Mecolaesthus Simon, 1893; Caruaya GS, 2011 = Mesabolivar
GS, 1998; Coroia GS, 2005 = Artema Walckenaer, 1837; Maimire GS, 2009 =
Mecolaesthus Simon, 1893; Moraia GS, 2011 = Mecolaesthus Simon, 1893; Nasuta GS,
2009 = Mecolaesthus Simon, 1893; Portena GS, 2011 = Metagonia Simon, 1893;
Rioparaguanus GS, 2005 = Mesabolivar GS, 1998; Tonoro GS, 2009 = Litoporus Simon,
1893; Sanluisi GS, 2003 = Mecolaesthus Simon, 1893. Three of the type species are
also specific synonyms: Autana autanensis GS, 2011 = Mesabolivar aurantiacus
(Mello-Leitao, 1930); Coroia magna GS, 2005 = Artema atlanta Walckenaer, 1837;
Tonoro multispinae GS, 2009 = Litoporus uncatus (Simon, 1893). Six species that
Gonzalez-Sponga described under Blechroscelis (a genus previously synonymized
with Priscula Simon, 1893) are all synonyms of Mesabolivar eberhardi Huber, 2000
(B. acuoso GS, 2011; B. araguanus GS, 2011; B. blechroscelis GS, 2011; B.
copeyensis GS, 2011; B. cordillerano GS, 2011; B. andinensis GS, 2011). In
addition, and unrelated to Gonzalez-Sponga's work, we synonymize the Central
Asian monotypic genus Ceratopholcus Spassky, 1934 with Crossopriza Simon, 1893;
we synonymize the Chinese species Pholcus acerosus Peng & Zhang, 2011 with
Pholcus fragillimus Strand, 1907 and remove the Malaysian monotypic genus Mystes
Bristowe, 1938, previously thought to be the only East Asian representative of
the subfamily Ninetinae, to the family Filistatidae.
PMID- 25112346
TI - Taxonomic revision of the semi-aquatic skink Parvoscincus leucospilos (Reptilia:
Squamata: Scincidae), with description of three new species.
AB - We review the recent discovery of multiple populations of the enigmatic, semi
aquatic Sphenomorphus Group skink, Parvoscincus leucospilos Peters, and
investigate the morphological and genetic diversity of isolated, allopatric
populations of this unique skink. Our investigations support the recognition of
four unique evolutionary lineages distributed across Luzon Island in the
Philippines, three of which are herein described as new species (P. tikbalangi
sp. nov., P. manananggalae sp. nov., and P. duwendorum sp. nov.). All four
recognized species are genetically divergent in both mitochondrial and nuclear
DNA sequences, and morphologically distinct. The description of three new Luzon
Island endemic species adds to the growing body of literature suggesting that
mechanisms driving the accumulation of vertebrate diversity in the Philippines
may vary regionally across the archipelago.
PMID- 25112348
TI - Cymatodera ochlera Barr, a junior synonym of Cymatodera wolcotti Barr, with a
comparison to similar species (Coleoptera: Cleridae).
AB - Cymatodera ochlera Barr 1972 has been considered to be very similar to but
distinct from C. wolcotti Barr 1950. We present evidence to show that these two
species are conspecific and C. ochlera should be treated as a junior synonym of
C. wolcotti. Cymatodera wolcotti is compared to C. balteata and C. undulata, two
species remarkably similar to C. wolcotti. Morphological characters of
significant value are presented that confirm C. balteata and C. undulata are
separate species. Images of all characters discussed are provided.
PMID- 25112349
TI - Two new species and a new synonym of the genus Paederus Fabricius (Coleoptera:
Staphylinidae: Paederinae) from China.
AB - Two new species of the genus Paederus Fabricius, 1775 from mainland China are
described: Paederus (Harpopaederus) brevior sp. nov. (Shaanxi) and P. (H.)
multidenticulatus sp. nov. (Hubei). One new synonym is proposed: Paederus
parvidenticulatus Li, Zhou & Solodovnikov, 2013 = Paederus symmetricus Li, Zhou &
Solodovnikov, 2013 syn. nov.
PMID- 25112350
TI - Nippontonia ashmoreiensis sp. nov., (Crustacea: Decapoda; Pontoniinae) from
Ashmore Reef, Western Australia.
AB - An undescribed species of pontoniine shrimp of the genus Nippontonia Bruce &
Bauer, N. ashmoriensis sp. nov., collected from a sponge from Ashmore Reef,
Western Australia, is described and illustrated.
PMID- 25112351
TI - Helicopsyche (Feropsyche) timbira sp. nov. (Trichoptera: Helicopsychidae), a new
species from southeastern Brazil.
PMID- 25112352
TI - Aphodius petri: a replacement name for the primary junior homonym Aphodius
kozlovi Frolov, 2009 (Coleoptera: Scarabaeidae: Aphodiinae).
PMID- 25112353
TI - Galkinius nom.nov., replacement name for Galkinia Ross & Newman, 1995.
PMID- 25112354
TI - Plume moths of Malawi (Lepidoptera: Pterophoridae).
AB - A review of Pterophoridae of Malawi is presented; 96 species from 35 genera and
five subfamilies are recorded. Fourteen species are described as new: Agdistis
nyasa Kovtunovich & Ustjuzhanin sp. nov., Platyptilia mugesse Kovtunovich &
Ustjuzhanin sp. nov., Stenoptilia juniper Kovtunovich & Ustjuzhanin sp. nov.,
Sphenarches mulanje Kovtunovich & Ustjuzhanin sp.nov., Marasmarcha lamborni
Kovtunovich & Ustjuzhanin sp. nov., Arcoptilia malawica Kovtunovich & Ustjuzhanin
sp. nov., Apoxyptilus uzumarus Kovtunovich & Ustjuzhanin sp. nov., Gypsochares
murphy Kovtunovich & Ustjuzhanin sp. nov., Crassuncus livingstoni Kovtunovich &
Ustjuzhanin sp. nov., Hellinsia namizimu Kovtunovich & Ustjuzhanin sp. nov.,
Hellinsia shewa Kovtunovich & Ustjuzhanin sp. nov., Picardia leza Kovtunovich &
Ustjuzhanin sp. nov., Picardia raymondi Kovtunovich & Ustjuzhanin sp. nov.,
Picardia tumbuka Kovtunovich & Ustjuzhanin sp. nov. New synonymies are
established for 10 species: Deuterocopus deltoptilus Meyrick, 1930 = Deuterocopus
socotranus Rebel, 1907 syn. nov.; Deuterocopus henrioti Bigot & Boireau, 2006 =
Deuterocopus socotranus Rebel, 1907 syn. nov.; Platyptilia periacta Meyrick, 1910
= Platyptilia farfarella Zeller, 1867 syn. nov.; Platyptilia claripicta Fletcher,
1910 = Platyptilia farfarella Zeller, 1867 syn. nov.; Platyptilia pygmaeana
Strand, 1913 = Sphenarches anisodactylus (Walker, 1864) syn. nov.; Exelastis
bergeri Bigot, 1969 = Exelastis crudipennis (Meyrick, 1932) syn. nov.;
Prichotilus tanzanicus Gielis, 2011 = Prichotilus tara Ustjuzhanin and
Kovtunovich, 2011 syn. nov.; Crassuncus chappuisi Gibeaux, 1994 = Crassuncus
ecstaticus (Meyrick, 1932) syn. nov.; Paulianilus lolibai Arenberger, 2011 =
Hellinsia madecasseus (Bigot, 1964) syn. nov.; Pterophorus purus Meyrick, 1913 =
Crassuncus pacifica (Meyrick, 1911) syn. nov. New combinations are established
for six species: Marasmarcha bengtssoni (Gielis, 2009) comb. nov.; Marasmarcha
locharcha (Meyrick, 1924) comb. nov.; Marasmarcha rubriacuta (Gielis, 2009) comb.
nov.; Procapperia insomnis (Townsend, 1956) comb. nov.; Crassuncus ecstaticus
(Meyrick, 1932) comb. nov.; Crassuncus colubratus (Meyrick, 1909) comb. nov. For
Stenoptilia viettei Gibeaux, 1994, Sphenarches bifurcatus Gielis, 2009,
Crassuncus ecstaticus (Meyrick, 1932) images of the male genitalia are presented
for the first time, for Marasmarcha bengtssoni (Gielis, 2009), and Stenodacma
cognata Gielis, 2009 female genitalia are illustrated for the first time. Species
of wide pantropical or cosmopolitan distribution are not reported as new for the
fauna of Malawi. However, 65 species of Pterophoridae are reported for the fauna
of Malawi for the first time. One of them, Stenoptilia viettei Gibeaux, 1994,
described from Madagascar, is reported for continental Africa for the first time.
PMID- 25112355
TI - The identity of the treehopper genus Dysyncritus Fowler, with descriptions of new
related taxa (Hemiptera: Membracidae: Heteronotinae).
AB - Dysyncritus Fowler is revised based on the examination of primary types, and
restructured to exclusively accomodate Dysyncritus intectus Fowler, 1895.
Allodrilus Evangelista gen. nov. (type species: Cymbomorpha nitidipennis
Funkhouser, 1922 = Allodrilus nitidipennis (Funkhouser, 1922) comb. nov.) is
erected with seven newly discovered taxa: A. alboferrugineus Evangelista sp. nov.
(Brazil, Colombia, Guyana), A. colombiensis Florez-V sp. nov. (Colombia), A.
deitzi Evangelista sp. nov. (Ecuador), A. granulatus Evangelista sp. nov.
(Ecuador), A. horizontalis Evangelista sp. nov. (Bolivia), A. intermedius
Evangelista sp. nov. (Ecuador), and A. similis Evangelista sp. nov. (Peru). A key
to males is provided, in addition to annotated descriptions and illustrations.
Nomenclatural changes are proposed to species formerly included in Dysyncritus:
Smiliorachis nubilis (Goding, 1930) comb. nov., Smiliorachis discrepans (Goding,
1930) comb. nov., and Dysyncritus lineatus Goding, 1930 (= Smiliorachis octilinea
Stal, 1869 syn. nov.).
PMID- 25112356
TI - Two new species of Cosmolaelaps Berlese (Acari:Laelapidae) from Iran .
AB - This paper reports on two species of mites of the genus Cosmolaelaps Berlese,
1903 in Iran--C. dorfakiensis sp. nov., and C. pinnatus sp. nov., extracted from
soil and leaf litter samples in Guilan Province, Northern Iran. A key to the
species of Cosmolaelaps occurring in the Iran is also provided.
PMID- 25112357
TI - Three new bee species of Rhophitulus Ducke (Hymenoptera, Apidae, Protandrenini)
from Argentina and Brazil.
AB - This work describes three newly discovered species of Rhophitulus Ducke, 1907: R.
labiosus n. sp. from Minas Gerais (Brazil), R. mimus n. sp. from Salta
(Argentina), and R. xenopalpus n. sp. from Catamarca and Tucuman (Argentina).
Photographs of the holotype of Rhophitulus steinbachi (Friese, 1916) are
provided, and modifications in the morphology of a female of R. xenopalpus n. sp.
when parasitized by Strepsiptera are recorded for the first time for the genus.
PMID- 25112358
TI - The first record of an association between a pontoniine shrimp (Crustacea:
Decapoda: Palaemonidae: Pontoniinae) and a thalassematid spoon worm (Echiura:
Thalassematidae), with the description of a new shrimp species.
AB - A new pontoniine shrimp species, Eupontonia nudirostris sp. nov. (Crustacea:
Decapoda: Palaemonidae: Pontoniinae), was found in association with the
thalassematid spoon worm Listriolobus sp. (Echiura: Thalassematidae) in the
mangrove littoral of Dam Bay of Tre Island, Nhatrang Bay, Vietnam. This is the
first record of an association between symbiotic pontoniine shrimp and spoon worm
as their host. The new shrimp species clearly differs from other representatives
of the genus Eupontonia Bruce, 1971 by the unarmed rostrum with a blunt tip and
the reduced antennal tooth on the carapace, which can be considered as an
adaptation to symbiotic lifestyle inside cramped burrows of the host. A revised
key to the genus Eupontonia Bruce, 1971 is presented.
PMID- 25112359
TI - Two new species of Cyta (Acari: Prostigmata: Bdellidae) from Western Iran .
AB - This paper reports two new species of Bdellidae, Cyta leliae sp. nov. and Cyta
kurdistanicus sp. nov., collected from soil and litter under oak trees, Quercus
brantii Lindl. (Fagaceae), wild almond, Amygdalus lycioides Spach (Rosaceae) and
grass, Kurdistan Province, Iran. A key is provided to adult female Cyta of the
world.
PMID- 25112360
TI - Swedish Plectida (Nematoda). Part 7. Setostephanolaimus tchesunovi sp. n. from
the west coast of Sweden.
AB - A new species of Setostephanolaimus, S. tchesunovi sp. n., is described from
bottom sediments collected in the Skagerrak and Gullmarn Fjord off the west coast
of Sweden. It is characterised by 1.0-1.3 mm long body, outer labial setae 6.5
8.5 um long, cephalic setae 9-11 um long, subcephalic setae 4-6 um long,
transversely-oval amphid, female with monodelphic opisthodelphic reproductive
system, male with 6-9 tubular and without alveolar supplements, spicules arcuate
and 54-64 um long, gubernaculum with dorsal apophysis. A tabular compendium and
dichotomous identification key to species of the genus Setostephanolaimus are
provided.
PMID- 25112361
TI - A fossil Paratrombiinae mite (Actinotrichida: Trombidioidea) from the Rovno
amber, Ukraine.
AB - The first description of a fossil representative of Paratrombiinae from the Rovno
amber, Paratrombium rovniense sp. nov., based on an unengorged larva, is
provided. The discovery results in a re-definition of the Paratrombiinae and of
Paratrombium, which also comprise species with two pectinalae on coxa I.
PMID- 25112362
TI - A new species of Petersitocoroides Brailovsky (Hemiptera: Heteroptera: Coreidae:
Coreini) from Peru.
AB - Petersitocoroides vergarae, a new species from Peru, is described and placed in
the tribe Coreini (Heteroptera). Dorsal illustrations and drawings of the
pronotum, head and male genitalia, as well as a key to the known species, are
provided.
PMID- 25112363
TI - A new species of the genus Mazaeras Walker, 1855 (Lepidoptera: Erebidae:
Arctiinae).
PMID- 25112364
TI - Decoration of silicon nanostructures with copper particles for simultaneous
selective capture and mass spectrometry detection of His-tagged model peptide.
AB - We present in this work a simple and fast preparation method of a new affinity
surface-assisted laser/desorption ionization mass spectrometry (SALDI-MS)
substrate based on silicon nanostructures decorated with copper particles. The
silicon nanostructures were fabricated by the metal-assisted chemical etching
(MACE) method. Then, superhydrophilic areas surrounded by superhydrophobic
regions were formed through hydrosilylation reaction of 1-octadecene, followed by
local degradation of the octadecyl layer. After that, copper particles were
deposited in the hydrophilic areas by using the electroless method. We have
demonstrated that these surfaces were able to perform high selective capture of
model His-tag peptide even in a complex mixture such as serum solution. Then, the
captured peptide was detected by mass spectrometry at a femtomolar level without
the need of organic matrix.
PMID- 25112365
TI - Protein S-glutathionylation: from current basics to targeted modifications.
AB - The interaction between antioxidant glutathione and the free thiol in susceptible
cysteine residues of proteins leads to reversible protein S-glutathionylation.
This reaction ensures cellular homeostasis control (as a common redox-dependent
post-translational modification associated with signal transduction) and
intervenes in oxidative stress-related cardiovascular pathology (as initiated by
redox imbalance). The purpose of this review is to evaluate the recent knowledge
on protein S-glutathionylation in terms of chemistry, broad cellular
intervention, specific quantification, and potential for therapeutic
exploitation. The data bases searched were Medline and PubMed, from 2009 to 2014
(term: glutathionylation). Protein S-glutathionylation ensures protection of
protein thiols against irreversible over-oxidation, operates as a biological
redox switch in both cell survival (influencing kinases and protein phosphatases
pathways) and cell death (by potentiation of apoptosis), and cross-talks with
phosphorylation and with S-nitrosylation. Collectively, protein S
glutathionylation appears as a valuable biomarker for oxidative stress, with
potential for translation into novel therapeutic strategies.
PMID- 25112367
TI - The evolution of boosting algorithms. From machine learning to statistical
modelling.
AB - BACKGROUND: The concept of boosting emerged from the field of machine learning.
The basic idea is to boost the accuracy of a weak classifying tool by combining
various instances into a more accurate prediction. This general concept was later
adapted to the field of statistical modelling. Nowadays, boosting algorithms are
often applied to estimate and select predictor effects in statistical regression
models. OBJECTIVES: This review article attempts to highlight the evolution of
boosting algorithms from machine learning to statistical modelling. METHODS: We
describe the AdaBoost algorithm for classification as well as the two most
prominent statistical boosting approaches, gradient boosting and likelihood-based
boosting for statistical modelling. We highlight the methodological background
and present the most common software implementations. RESULTS: Although gradient
boosting and likelihood-based boosting are typically treated separately in the
literature, they share the same methodological roots and follow the same
fundamental concepts. Compared to the initial machine learning algorithms, which
must be seen as black-box prediction schemes, they result in statistical models
with a straight-forward interpretation. CONCLUSIONS: Statistical boosting
algorithms have gained substantial interest during the last decade and offer a
variety of options to address important research questions in modern biomedicine.
PMID- 25112369
TI - Electronic structures and selective fluoride sensing features of Os(bpy)2(HL(2-))
and [{Os(bpy)2}2(MU-HL(2-))](2+) (H3L: 5-(1H-benzo[d]imidazol-2-yl)-1H-imidazole
4-carboxylic acid).
AB - The article deals with the newly designed mononuclear and asymmetric dinuclear
osmium(ii) complexes Os(II)(bpy)2(HL(2-)) (1) and [(bpy)2Os(II)(MU-HL(2
))Os(II)(bpy)2](Cl)2 ([2](Cl)2)/[(bpy)2Os(II)(MU-HL(2-))Os(II)(bpy)2](ClO4)2
([2](ClO4)2), respectively, (H3L = 5-(1H-benzo[d]imidazol-2-yl)-1H-imidazole-4
carboxylic acid and bpy = 2,2'-bipyridine). The identity of 1 has been
established by its single crystal X-ray structure. The ligand (HL(2-))-based
primary oxidation process (E, 0.23 V versus SCE) along with the partial metal
contribution (~20%) in 1 has been revealed by the ligand-dominated HOMO of 1
(HL(2-): 88%, Os: 8%), as well as by the Mulliken spin density distribution of
1(+) (HL(2-): 0.878, Os: 0.220). Accordingly, 1(+) exhibits a free radical type
EPR at 77 K with a partial metal-based anisotropic feature (g1 = 2.127, g2 =
2.096, g3 = 2.046; = 2.089; Deltag = 0.08). (1)H-NMR of the dinuclear 2(2+)
in CDCl3 suggests an intimate mixture of two diastereomeric forms in a 1 : 1
ratio. The DFT-supported predominantly Os(ii)/Os(iii)-based couples of asymmetric
2(2+) at 0.24 V and 0.50 V versus SCE result in a comproportionation constant
(Kc) value of 8.2 * 10(4). The class I mixed valent state of 2(3+) (S = 1/2) has,
however, been corroborated by the Mulliken spin density distribution of Os1:
0.887, Os2: 0.005, HL(2-): 0.117, as well as by the absence of a low-energy IVCT
(intervalence charge transfer) band in the near-IR region (up to 2000 nm). The
appreciable spin accumulation on the bridge in 2(3+) or 2(4+) (S = 1, Os1: 0.915,
Os2: 0.811 and HL(2-): 0.275) implies a mixed electronic structural form of
[(bpy)2Os(III)(MU-HL(2-))Os(II)(bpy)2](3+)(major)/[(bpy)2Os(II)(MU-HL(
))Os(II)(bpy)2](3+)(minor) or [(bpy)2Os(III)(MU-HL(2
))Os(III)(bpy)2](4+)(major)/[(bpy)2Os(III)(MU-HL(-))Os(II)(bpy)2](4+) (minor),
respectively. The mixed valent {Os(III)(MU-HL(2-))Os(II)} state in 2(3+),
however, fails to show EPR at 77 K due to the rapid spin relaxation process. The
DFT-supported bpy-based two reductions for both 1(+) and 2(2+) appear in the
potential range of -1.5 V to -1.8 V versus SCE. The electronic transitions in
1(n) and 2(n) are assigned by the TD-DFT calculations. Furthermore, the potential
anion sensing features of 1 and 2(2+)via the involvement of the available N-H
proton in the framework of coordinated HL(2-) have been evaluated by different
experimental investigations, in conjunction with the DFT calculations, using a
wide variety of anions such as F(-), Cl(-), Br(-), I(-), OAc(-), SCN(-), HSO4(-)
and H2PO4(-). This, however, establishes that both 1 and 2(2+) are equally
efficient in recognising the F(-) ion selectively, with log K values of 6.83 and
5.89, respectively.
PMID- 25112368
TI - Globalization of leptospirosis through travel and migration.
AB - Leptospirosis remains the most widespread zoonotic disease in the world, commonly
found in tropical or temperate climates. While previous studies have offered
insight into intra-national and intra-regional transmission, few have analyzed
transmission across international borders. Our review aimed at examining the
impact of human travel and migration on the re-emergence of Leptospirosis.
Results suggest that alongside regional environmental and occupational exposure,
international travel now constitute a major independent risk factor for disease
acquisition. Contribution of travel associated leptospirosis to total caseload is
as high as 41.7% in some countries. In countries where longitudinal data is
available, a clear increase of proportion of travel-associated leptospirosis over
the time is noted. Reporting patterns is clearly showing a gross underestimation
of this disease due to lack of diagnostic facilities. The rise in global travel
and eco-tourism has led to dramatic changes in the epidemiology of Leptospirosis.
We explore the obstacles to prevention, screening and diagnosis of Leptopirosis
in health systems of endemic countries and of the returning migrant or traveler.
We highlight the need for developing guidelines and preventive strategies of
Leptospirosis related to travel and migration, including enhancing awareness of
the disease among health professionals in high-income countries.
PMID- 25112370
TI - Characteristics of evodiamine-exerted stimulatory effects on rat jejunal
contractility.
AB - This study was designed to characterise the effects of evodiamine on intestinal
contractility and reveal the correlated mechanisms. Evodiamine (2.5-80.0 MUM)
increased normal jejunal contractility and jejunal hypocontractility established
under a variety of experimental conditions. Evodiamine-exerted stimulatory
effects were blocked by the L-type Ca(2+) channel blocker nifedipine or abolished
in the Ca(2+)-free assay condition. The stimulatory effects of evodiamine on
jejunal contractility were partially blocked in the presence of neurotoxin
tetrodotoxin or endogenous acetylcholine synthesis blocker hemicholinium-3 or
muscarinic receptor antagonist atropine, respectively. Evodiamine-exerted
stimulatory effects were blocked by c-kit receptor tyrosine kinase inhibitor
imatinib. Evodiamine increased myosin phosphorylation in jejunal smooth muscle of
constipation-prominent rats. These results showed that evodiamine-exerted
stimulatory effects on jejunal segments are Ca(2+)-dependent, need the presence
of interstitial cell of Cajal, requirement of cholinergic neuron and correlate
with increased myosin phosphorylation, implicating the potential value of
evodiamine in relieving hypo-motility disorders.
PMID- 25112371
TI - A retrospective study of short- and long-term effects on renal function after
acute renal infarction.
AB - PURPOSE: Acute renal infarction is often missed or diagnosed late due to its
rarity and non-specific clinical manifestations. This study analyzed the clinical
and laboratory findings of patients diagnosed with renal infarction to determine
whether it affects short- or long-term renal prognosis. METHODS: We
retrospectively reviewed the medical records of 100 patients diagnosed as acute
renal infarction from January 1995 to September 2012 at Gyeongsang National
University Hospital, Jinju, South Korea. RESULTS: Acute kidney injury (AKI)
occurred in 30 patients. Infarct size was positively correlated with the
occurrence of AKI (p = 0.004). Compared with non-AKI patients, AKI occurrence was
significantly correlated with degree of proteinuria (p < 0.001) and the presence
of microscopic hematuria (p = 0.035). AKI patients had higher levels of aspartate
transaminase (p < 0.001), alanine transaminase (p < 0.001), and lactated
dehydrogenase (p = 0.027). AKI after acute renal infarction was more common in
patients with chronic renal failure (CRF) (eGFR < 60 mL/min), compared with non
CRF patients, whose baseline eGFR was >60 mL/min (p = 0.003). Most patients
recovered from AKI, except for seven patients (7%) who developed persistent renal
impairment (chronic kidney disease progression) closely correlated with magnitude
of infarct size (p = 0.015). Six AKI patients died due to combined comorbidity.
CONCLUSIONS: AKI is often associated with acute renal infarction. Although most
AKI recovers spontaneously, renal impairment following acute renal infarction can
persist. Thus, early diagnosis and intervention are needed to preserve renal
function.
PMID- 25112372
TI - The influence of vitamin D analogs on calcification modulators, N-terminal pro-B
type natriuretic peptide and inflammatory markers in hemodialysis patients: a
randomized crossover study.
AB - BACKGROUND: The risk of cardiovascular disease is tremendously high in dialysis
patients. Dialysis patients treated with vitamin D analogs show decreased
cardiovascular morbidity and mortality compared with untreated patients. We
examined the influence of two common vitamin D analogs, alfacalcidol and
paricalcitol, on important cardiovascular biomarkers in hemodialysis patients.
Anti-inflammatory effects and the influence on regulators of vascular
calcification as well as markers of heart failure were examined. METHODS: In 57
chronic hemodialysis patients enrolled in a randomized crossover trial comparing
paricalcitol and alfacalcidol, we examined the changes in osteoprotegerin, fetuin
A, NT-proBNP, hs-Crp, IL-6 and TNF-alpha, during 16 weeks of treatment. RESULTS:
NT-proBNP and osteoprotegerin increased comparably in the paricalcitol and
alfacalcidol-treated groups. Fetuin-A increased significantly in the alfacalcidol
treated group compared with the paricalcitol-treated group (difference 32.84
MUmol/l (95% C.I.; range 0.21-67.47)) during the first treatment period. No
difference was found between the groups during the second treatment period, and
IL-6, TNF-alpha and hs-Crp were unchanged in both treatment groups. CONCLUSIONS:
Paricalcitol and alfacalcidol modulate regulators of vascular calcification.
Alfacalcidol may increase the level of the calcification inhibitor fetuin-A. We
did not find any anti-inflammatory effect or difference in changes of NT-proBNP.
TRIAL REGISTRY: ClinicalTrials.gov NCT00469599 May 3 2007.
PMID- 25112375
TI - A distinct immunogenic region of glutamic acid decarboxylase 65 is naturally
processed and presented by human islet cells to cytotoxic CD8 T cells.
AB - CD8 T cells specific for islet autoantigens are major effectors of beta cell
damage in type 1 diabetes, and measurement of their number and functional
characteristics in blood represent potentially important disease biomarkers. CD8
T cell reactivity against glutamic acid decarboxylase 65 (GAD65) in HLA-A*0201
subjects has been reported to focus on an immunogenic region 114-123
(VMNILLQYVV), with studies demonstrating both 114-123 and 114-122 epitopes being
targeted. However, the fine specificity of this response is unclear and the key
question as to which epitope(s) beta cells naturally process and present and,
therefore, the pathogenic potential of CD8 T cells with different specificities
within this region has not been addressed. We generated human leucocyte antigen
(HLA)-A*0201-restricted CD8 T cell clones recognizing either 114-122 alone or
both 114-122 and 114-123. Both clone types show potent and comparable effector
functions (cytokine and chemokine secretion) and killing of indicator target
cells externally pulsed with cognate peptide. However, only clones recognizing
114-123 kill target cells transfected with HLA-A*0201 and GAD2 and HLA-A*0201(+)
human islet cells. We conclude that the endogenous pathway of antigen processing
by HLA-A*0201-expressing cells generates GAD65114-123 as the predominant epitope
in this region. These studies highlight the importance of understanding beta cell
epitope presentation in the design of immune monitoring for potentially
pathogenic CD8 T cells.
PMID- 25112373
TI - New subfamilies of major intrinsic proteins in fungi suggest novel transport
properties in fungal channels: implications for the host-fungal interactions.
AB - BACKGROUND: Aquaporins (AQPs) and aquaglyceroporins (AQGPs) belong to the
superfamily of Major Intrinsic Proteins (MIPs) and are involved in the transport
of water and neutral solutes across the membranes. MIP channels play significant
role in plant-fungi symbiotic relationship and are believed to be important in
host-pathogen interactions in human fungal diseases. In plants, at least five
major MIP subfamilies have been identified. Fungal MIP subfamilies include
orthodox aquaporins and five subgroups within aquaglyceroporins. XIP subfamily is
common to both plants and fungi. In this study, we have investigated the extent
of diversity in fungal MIPs and explored further evolutionary relationships with
the plant MIP counterparts. RESULTS: We have extensively analyzed the available
fungal genomes and examined nearly 400 fungal MIPs. Phylogenetic analysis and
homology modeling exhibit the existence of a new MIP cluster distinct from any of
the known fungal MIP subfamilies. All members of this cluster are found in
microsporidia which are unicellular fungal parasites. Members of this family are
small in size, charged and have hydrophobic residues in the aromatic/arginine
selectivity filter and these features are shared by small and basic intrinsic
proteins (SIPs), one of the plant MIP subfamilies. We have also found two new
subfamilies (delta and gamma2) within the AQGP group. Fungal AQGPs are the most
diverse and possess the largest number of subgroups. We have also identified
distinguishing features in loops E and D in the newly identified subfamilies
indicating their possible role in channel transport and gating. CONCLUSIONS:
Fungal SIP-like MIP family is distinct from any of the known fungal MIP families
including orthodox aquaporins and aquaglyceroporins. After XIPs, this is the
second MIP subfamily from fungi that may have possible evolutionary link with a
plant MIP subfamily. AQGPs in fungi are more diverse and possess the largest
number of subgroups. The aromatic/arginine selectivity filter of SIP-like fungal
MIPs and the delta AQGPs are unique, hydrophobic in nature and are likely to
transport novel hydrophobic solutes. They can be attractive targets for
developing anti-fungal drugs. The evolutionary pattern shared with their plant
counterparts indicates possible involvement of new fungal MIPs in plant-fungi
symbiosis and host-pathogen interactions.
PMID- 25112374
TI - Features of the built environment related to physical activity friendliness and
children's obesity and other risk factors.
AB - OBJECTIVES: We investigated the relationships among environmental features of
physical activity friendliness, socioeconomic indicators, and prevalence of
obesity (BMI status), central adiposity (waist circumference, waist-height
ratio), and hypertension. DESIGN AND SAMPLE: The design was cross-sectional; the
study was correlational. The sample was 911 kindergarteners through sixth graders
from three schools in an urban school district residing in 13 designated
neighborhoods. MEASURES: Data from walking environmental community audits, census
data for socioeconomic indicators, body mass index, waist circumference, waist
height ratio, and blood pressure were analyzed. A modified Alfonzo's Hierarchy of
Walking Needs model was the conceptual framework for environmental features
(i.e., accessibility, safety, comfort, and pleasurability) related to physical
activity. RESULTS: Accessibility was significantly and negatively correlated with
prevalence of obesity and with prevalence of a waist-height ratio >0.50. When
neighborhood education was controlled, and when both neighborhood education and
poverty were controlled with partial correlational analysis, comfort features of
a walking environment were significantly and positively related to prevalence of
obesity. When poverty was controlled with partial correlation, accessibility was
significantly and negatively correlated with prevalence of waist-height ratio
>0.50. CONCLUSIONS: The built environment merits further research to promote
physical activity and stem the obesity epidemic in children. Our approach can be
a useful framework for future research.
PMID- 25112377
TI - Variants associated with type 2 diabetes identified by the transethnic meta
analysis study: assessment in American Indians and evidence for a new signal in
LPP.
AB - AIM/HYPOTHESIS: A recent genome-wide trans-ancestry meta-analysis identified
seven new loci associated with type 2 diabetes. We assessed the replication of
the seven lead single nucleotide polymorphisms (SNPs) and evaluated these loci
for additional signals in American Indians. METHODS: Seven SNPs were genotyped in
7,710 individuals from a longitudinally studied American Indian population, and
associations with type 2 diabetes, BMI and related phenotypes were assessed.
Previous genome-wide association study (GWAS) data from these individuals were
used to screen for additional type 2 diabetes signals at these loci. A variant
independent of the trans-ancestry meta-analysis was identified within LPP, and
its replication was assessed in an additional 3,106 urban American Indians.
RESULTS: SNP rs6813195 near to TMEM154 was nominally associated with type 2
diabetes (p = 0.01, OR 1.12 [95% CI 1.03, 1.22]) and adiposity: the type 2
diabetes risk allele was associated with a lower percentage body fat (beta =
1.451%, p = 4.8 * 10(-4)). Another SNP, rs3130501 near to POU5F1-TCF19, was
associated with BMI (beta = -0.012, p = 0.004), type 2 diabetes adjusted for BMI
(p = 0.02, OR 1.11 [95% CI 1.02, 1.22]), 2 h glucose concentrations (beta = 0.080
mmol/l, p = 0.02) and insulin resistance estimated by homeostatic model (beta =
0.039, p = 0.009). The independent variant identified at the LPP locus in our
American Indian GWAS for type 2 diabetes was replicated in the additional samples
(all American Indian meta-analysis, p = 8.9 * 10(-6), OR 1.29 [95% CI 1.15,
1.45]). CONCLUSIONS/INTERPRETATION: For two of the seven newly identified
variants, there was nominal evidence for association with type 2 diabetes and
related traits in American Indians. Identification of an independent variant at
the LPP locus suggests the existence of more than one type 2 diabetes signal at
this locus.
PMID- 25112376
TI - RANKL-OPG and RAGE modulation in vascular calcification and diabetes: novel
targets for therapy.
AB - Type 2 diabetes is associated with increased cardiovascular morbidity and
mortality and early vascular ageing. This takes the form of atherosclerosis, with
progressive vascular calcification being a major complication in the pathogenesis
of this disease. Current research and drug targets in diabetes have hitherto
focused on atherosclerosis, but vascular calcification is now recognised as an
independent predictor of cardiovascular morbidity and mortality. An emerging
regulatory pathway for vascular calcification in diabetes involves the receptor
activator for nuclear factor kappaB (RANK), RANK ligand (RANKL) and
osteoprotegerin (OPG). Important novel biomarkers of calcification are related to
levels of glycation and inflammation in diabetes. Several therapeutic strategies
could have advantageous effects on the vasculature in patients with diabetes,
including targeting the RANKL and receptor for AGE (RAGE) signalling pathways,
since there has been little success-at least in macrovascular outcomes-with
conventional glucose-lowering therapy. There is substantial and relevant clinical
and basic science evidence to suggest that modulating RANKL-RANK-OPG signalling,
RAGE signalling and the associated proinflammatory milieu alters the natural
course of cardiovascular complications and outcomes in people with diabetes.
However, further research is critically needed to understand the precise
mechanisms underpinning these pathways, in order to translate the anti
calcification strategies into patient benefit.
PMID- 25112378
TI - The effects of UV-B radiation intensity on biochemical parameters and active
ingredients in flowers of Qi chrysanthemum and Huai chrysanthemum.
AB - The article studied UV-B effects on biochemical parameters and active ingredients
in flowers of Qi chrysanthemum and Huai chrysanthemum during the bud stage. The
experiment included four UV-B radiation levels (CK, ambient UV-B; T1, T2 and T3
indicated a 5%, 10% and 15% increase in ambient UV-BBE, respectively) to
determine the optimal UV-B radiation intensity in regulating active ingredients
level in flowers of two chrysanthemum varieties. Flower dry weight of two
cultivars was not affected by UV-B radiation under experimental conditions
reported here. UV-B treatments significantly increased the rate of superoxide
radical production, hydrogen peroxide (H2O2) (except for T1) and malondialdehyde
concentration in flowers of Huai chrysanthemum and H2O2 concentration in flowers
of Qi chrysanthemum. T2 and T3 treatments induced a significant increase in
phenylalanine ammonia lyase enzyme (PAL) activity, anthocyanins, proline,
ascorbic acid, chlorogenic acid and flavone content in flowers of two
chrysanthemum varieties, and there were no significant differences in PAL
activity, ascorbic acid, flavone and chlorogenic acid content between the two
treatments. These results indicated that appropriate UV-B radiation intensity did
not result in the decrease in flower yield, and could regulate PAL activity and
increase active ingredients content in flowers of two chrysanthemum varieties.
PMID- 25112379
TI - Genetics: New molecular classification of gastric adenocarcinoma proposed by The
Cancer Genome Atlas.
PMID- 25112381
TI - Herniated gravid uterus growing in an incisional hernia: study of three cases.
PMID- 25112382
TI - Gentamicin for prevention of intraoperative mesh contamination: demonstration of
high bactericide effect (in vitro) and low systemic bioavailability (in vivo).
AB - INTRODUCTION: Mesh infection is a severe complication after incisional hernia
repair and occurs in 1-3 % of all open mesh implantations. For this reason,
topical antimicrobial agent applied directly to the mesh is often used procedure.
So far, however, this procedure lacks a scientific basis. MATERIALS AND METHODS:
Two different meshes (ParietexTM, Covidien; UltraproTM, Ethicon Johnson &
Johnson) were incubated with increasing amounts of three different Staphylococcus
aureus strains (ATCC 25923; Mu50; ST239) with or without gentamicin and growth
ability were determined in vitro. To further address the question of the systemic
impact of topic gentamicin, serum levels were analyzed 6 and 24 h after
implantation of gentamicin-impregnated multifilament meshes in 19 patients.
RESULTS: None of the gentamicin-impregnated meshes showed any bacterial growth in
vitro. This effect was independent of the mesh type for all the tested S. aureus
strains. In the clinical setting, serum gentamicin levels 6 h after implantation
of the gentamicin-impregnated meshes were below the through-level (range 0.4-2.9
mg/l, mean 1.2 +/- 0.7 mg/l). After 24 h the gentamicin serum levels in all
patients had declined 90-65 % of the 6 h values. CONCLUSION: Local application of
gentamicin to meshes can completely prevent the growth of even gentamicin
resistant S. aureus strains in vitro. The systemic relevance of gentamicin in the
clinical controls showed to be very low, without reaching therapeutic
concentrations.
PMID- 25112380
TI - Tracking and quantification of dendritic cell migration and antigen trafficking
between the skin and lymph nodes.
AB - Skin-derived dendritic cells (DCs) play a crucial role in the maintenance of
immune homeostasis due to their role in antigen trafficking from the skin to the
draining lymph nodes (dLNs). To quantify the spatiotemporal regulation of skin
derived DCs in vivo, we generated knock-in mice expressing the photoconvertible
fluorescent protein KikGR. By exposing the skin or dLN of these mice to violet
light, we were able to label and track the migration and turnover of endogenous
skin-derived DCs. Langerhans cells and CD103(+)DCs, including
Langerin(+)CD103(+)dermal DCs (DDCs), remained in the dLN for 4-4.5 days after
migration from the skin, while CD103(-)DDCs persisted for only two days.
Application of a skin irritant (chemical stress) induced a transient >10-fold
increase in CD103(-)DDC migration from the skin to the dLN. Tape stripping
(mechanical injury) induced a long-lasting four-fold increase in CD103(-)DDC
migration to the dLN and accelerated the trafficking of exogenous protein
antigens by these cells. Both stresses increased the turnover of CD103(-)DDCs
within the dLN, causing these cells to die within one day of arrival. Therefore,
CD103(-)DDCs act as sentinels against skin invasion that respond with increased
cellular migration and antigen trafficking from the skin to the dLNs.
PMID- 25112383
TI - A detailed analysis of outcome reporting from randomised controlled trials and
meta-analyses of inguinal hernia repair.
AB - INTRODUCTION: Evidence is needed to justify whether investment in an
internationally agreed core outcome set for inguinal hernia surgery is needed.
This study aimed to assess outcome reporting from randomised controlled trials
(RCTs) and meta-analyses in inguinal hernia surgery. METHODS: RCTs and meta
analyses comparing surgical technique or mesh type for primary inguinal hernia
repair were systematically identified. Verbatim details, type, frequency and
definition of clinician-observed and -assessed outcomes were summarised. Patient
reported outcome measures (PROMs) were analysed for instrument validity and
frequency of domain reporting. RESULTS: 40 RCTs (10,810 patients) and 7 meta
analyses (17,280 patients) were identified. No single PROM was reported by all
studies. There were 58 different clinician-observed outcomes, with recurrence (n
= 47, 100%), wound infection (n = 33, 70.2%), haematoma (n = 31, 77.5%) and
seroma formation (n = 22, 46.8%) being most frequently reported. All studies
measured patients' views, although only 12 (30.0%) used validated instruments.
The SF36 was the most commonly used multi-dimensional valid PROM (n = 7), and a
visual analogue scale assessing pain (n = 32) was the most frequently used
unidimensional scale. Non-validated questionnaires assessed 25 other aspects of
patients' health. Two meta-analyses defined recurrence and three chronic pain
although neither ensured that included RCTs adhered to the definitions.
CONCLUSIONS: Outcome reporting from RCTs concerning inguinal hernia repair is
inconsistent and poorly defined, limiting meta-analyses, which themselves do not
control for the differing definitions of assessed outcomes. This study justifies
investment in a standardised core outcome set for inguinal hernia surgery, to
improve outcome reporting and evidence synthesis.
PMID- 25112384
TI - Small bowel obstruction after TAPP repair caused by a self-anchoring barbed
suture device for peritoneal closure: case report and review of the literature.
AB - INTRODUCTION: Transabdominal preperitoneal hernioplasty (TAPP) is a common
procedure for groin hernia repair in adults. The peritoneal closure after mesh
placement can be performed in various ways. In any case, thorough closure is
recommended to avoid mesh exposure to the viscera with the risk of adhesions and
bowel incarceration into peritoneal defects. Postoperative intestinal
obstructions can mainly occur due to adhesions or bowel herniation through
peritoneal defects into the dissected preperitoneal space. Incarcerations can
also occur as a consequence of trocar site herniation. RESULTS AND CONCLUSION:
Recently barbed self-anchoring knotless suturing devices are frequently used for
peritoneal closure. The correct handling of such sutures is crucial to avoid
potential complications. Despite of accurate management, bowel adherence and
injuries or volvulus can occur. METHODS: We present an unusual case of a
postoperative small bowel obstruction owing to strained adhesions and ingrowth
between a small bowel segment and a polyglyconate unidirectional self-anchoring
barbed suture device. Medline and PudMed databases were searched using the below
mentioned keywords and the literature on efficacy and safety of barbed sutures
for peritoneal closure is reviewed as well as the usage of such devices in other
fields of surgery.
PMID- 25112386
TI - Sportsman's groin: reaching a consensus.
PMID- 25112385
TI - Parastomal hernia repair with a 3-D mesh device and additional flat mesh repair
of the abdominal wall.
AB - PURPOSE: Parastomal hernias (PSHs) have been a major clinical problem. The aim of
this study was to evaluate a new method of PSH repair in combination with an
additional flat mesh reinforcement of the abdominal wall. METHODS: In a pilot
case series, seven patients suffering from complex PSHs (>=5 cm diameter and/or
recurrence) underwent surgery and were treated by intraperitoneal onlay technique
(IPOM) with a synthetic 3-D funnel-shaped mesh implant. The demographics,
perioperative, and follow-up data are presented in this report. RESULTS: The
surgical strategy varied between purely laparoscopic (n = 1), laparoscopically
assisted (hybrid n = 3), or open techniques (n = 3) using original or suture
reconstructed mesh devices. The funnel mesh implantations in IPOM technique were
combined with attached flat meshes in the appropriate position of the abdominal
wall. No procedure-related complications occurred. The mean length of hospital
stay was 12 days and the mean operating time was 171 min. No recurrence of PSH or
incisional hernias was observed during a mean follow-up period of 12.3 months
(range from 7 to 22). CONCLUSION: The use of a 3-D mesh implant has so far shown
to be a promising option in the treatment of primary and recurrent PSHs. Its use
proved to be reasonable in both laparoscopic and open IPOM technique. PSHs were
preferably repaired using the original, unmodified implant, but when we also
found it safe to incise, place and then suture the mesh around the pre-existing
ostomy.
PMID- 25112387
TI - Look carefully to the heels! A potentially treatable cause of spastic paraplegia.
PMID- 25112388
TI - Barth syndrome without tetralinoleoyl cardiolipin deficiency: a possible
ameliorated phenotype.
AB - Barth syndrome (BTHS) is an X-linked disorder characterised by cardiac and
skeletal myopathy, growth delay, neutropenia and 3-methylglutaconic aciduria (3
MGCA). Patients have TAZ gene mutations which affect metabolism of cardiolipin,
resulting in low tetralinoleoyl cardiolipin (CL(4)), an increase in its
precursor, monolysocardiolipin (MLCL), and an increased MLCL/CL(4) ratio. During
development of a diagnostic service for BTHS, leukocyte CL(4) was measured in 156
controls and 34 patients with genetically confirmed BTHS. A sub-group of seven
subjects from three unrelated families was identified with leukocyte CL(4)
concentrations within the control range. This had led to initial false negative
disease detection in two of these patients. MLCL/CL(4) in this subgroup was lower
than in other BTHS patients but higher than controls, with no overlap between the
groups. TAZ gene mutations in these families are all predicted to be
pathological. This report describes the clinical histories of these seven
individuals with an atypical phenotype: some features were typical of BTHS (five
have had cardiomyopathy, one family has a history of male infant deaths, three
have growth delay and five have 3-MGCA) but none has persistent neutropenia, five
have excellent exercise tolerance and two adults are asymptomatic. This report
also emphasises the importance of measurement of MLCL/CL(4) ratio rather than
CL(4) alone in the biochemical diagnosis of the BTHS.
PMID- 25112389
TI - Ten years of the international Pompe survey: patient reported outcomes as a
reliable tool for studying treated and untreated children and adults with non
classic Pompe disease.
AB - Pompe disease is a rare, progressive lysosomal storage disorder for which enzyme
therapy (ERT) became available in 2006. Four years earlier, the IPA/Erasmus MC
survey, an international longitudinal prospective survey, was established to
collect information on the natural course of the disease and its burden on
patients. The survey is a collaboration between Erasmus MC University Medical
Center and the International Pompe Association (IPA) and comprises an annual
questionnaire that was specifically designed to assess the symptoms and problems
of the disease. Here we review our results of over 10 years of follow-up, and
discuss the survey's contribution to the field. Tracking 408 Pompe patients
between 2002 and 2013, the cumulative data reveals the broad range of clinical
manifestations that interfere with patients' lives. The survey allowed us to
quantify the rate of disease progression and the positive effects of ERT on
patients' quality of life, fatigue, and participation in daily life. Furthermore,
it showed for the first time that survival is reduced in adult Pompe disease and
improved by ERT. Our results show that a patient survey can serve as a valuable
and reliable tool for obtaining quantifiable information on the natural course of
a rare disease and on the effects of therapy in a large cohort over a very long
time. Most importantly, by working with patient reported outcomes, the survey
provides the data that is truly relevant to the patient and complementary to
clinical datasets.
PMID- 25112392
TI - In vivo expression of recombinant pregnancy-specific glycoprotein 1a inhibits the
symptoms of collagen-induced arthritis.
AB - PROBLEM: The contribution of Pregnancy-specific glycoproteins (PSG), the major
variant of PSG released into the circulation during pregnancy, to the pregnancy
dependent improvement of rheumatoid arthritis (RA) has still not been elucidated.
METHOD OF STUDY: Collagen-induced arthritis (CIA) was used to test the hypothesis
that PSG1a when released into circulation has a modulatory role on the Th1
pathogenic response, thus improving the CIA symptoms. In vivo expression of PSG1a
was induced by injection of the vaccinia (Vac)-based expression vector harboring
the complete open-reading frame of PSG1a cDNA. RESULTS: In vivo PSG1a expression
during the induction of CIA ameliorated the clinical symptoms, thereby reducing
the arthritis score and incidence. Significantly lower levels of IL-17, IL-6, and
IFN-gamma, but higher levels of TGF-beta and IL-10 were secreted by collagen type
II-stimulated spleen mononuclear cells from Vac-PSG1a-treated mice compared with
control mice. Moreover, Vac-PSG1a treatment promoted the increase in splenic
CD4+CD25+Foxp3+ Treg cells. CONCLUSION: Pre-clinical Vac-PSG1a treatment
suppressed the Th1- and Th17-type-specific responses, leading to an increase in
splenic Treg cells as well as IL-10- and TGF-beta-secreting cells, with the CIA
symptoms being ameliorated.
PMID- 25112393
TI - Super-size me: self biases increase to larger stimuli.
AB - Prior work has shown that simple perceptual match responses to pairings of shapes
and labels are more efficient if the pairing is associated with the participant
(e.g., circle-you) than if it is associated with another familiar person (e.g.,
square-friend). There is a similar advantage for matching associations with high
value rewards (circle-L9) versus low-value rewards (square-L1) (Sui, He, &
Humphreys Journal of Experimental Psychology: Human Perception and Performance,
38, 1105-1117, 2012). Here we evaluated the relations between the self- and
reward-bias effects by introducing occasional trials in which the size of a shape
was varied unexpectedly (large or small vs. a standard medium). Participants
favored stimuli that were larger than the standard when stimuli were associated
with the self, and this enhancement of self bias was predicted by the degree of
self bias that participants showed to standard (medium) sized stimuli. Although
we observed a correlation between the magnitudes of the self and reward biases
over participants, reward-bias effects were not increased to large stimuli. The
data suggest both overlapping and independent components of the self and reward
biases, and that self biases are uniquely enhanced when stimuli increase in size,
consistent with previously reported motivational biases favoring large stimuli.
PMID- 25112391
TI - Adenylosuccinate lyase deficiency.
AB - Adenylosuccinate lyase ADSL) deficiency is a defect of purine metabolism
affecting purinosome assembly and reducing metabolite fluxes through purine de
novo synthesis and purine nucleotide recycling pathways. Biochemically this
defect manifests by the presence in the biologic fluids of two dephosphorylated
substrates of ADSL enzyme: succinylaminoimidazole carboxamide riboside (SAICAr)
and succinyladenosine (S-Ado). More than 80 individuals with ADSL deficiency have
been identified, but incidence of the disease remains unknown. The disorder shows
a wide spectrum of symptoms from slowly to rapidly progressing forms. The fatal
neonatal form has onset from birth and presents with fatal neonatal
encephalopathy with a lack of spontaneous movement, respiratory failure, and
intractable seizures resulting in early death within the first weeks of life.
Patients with type I (severe form) present with a purely neurologic clinical
picture characterized by severe psychomotor retardation, microcephaly, early
onset of seizures, and autistic features. A more slowly progressing form has also
been described (type II, moderate or mild form), as having later onset, usually
within the first years of life, slight to moderate psychomotor retardation and
transient contact disturbances. Diagnosis is facilitated by demonstration of
SAICAr and S-Ado in extracellular fluids such as plasma, cerebrospinal fluid
and/or followed by genomic and/or cDNA sequencing and characterization of mutant
proteins. Over 50 ADSL mutations have been identified and their effects on
protein biogenesis, structural stability and activity as well as on purinosome
assembly were characterized. To date there is no specific and effective therapy
for ADSL deficiency.
PMID- 25112394
TI - Spatial resolution in visual memory.
AB - Representations in visual short-term memory are considered to contain relatively
elaborated information on object structure. Conversely, representations in
earlier stages of the visual hierarchy are thought to be dominated by a sensory
based, feed-forward buildup of information. In four experiments, we compared the
spatial resolution of different object properties between two points in time
along the processing hierarchy in visual short-term memory. Subjects were asked
either to estimate the distance between objects or to estimate the size of one of
the objects' features under two experimental conditions, of either a short or a
long delay period between the presentation of the target stimulus and the probe.
When different objects were referred to, similar spatial resolution was found for
the two delay periods, suggesting that initial processing stages are sensitive to
object-based properties. Conversely, superior resolution was found for the short,
as compared with the long, delay when features were referred to. These findings
suggest that initial representations in visual memory are hybrid in that they
allow fine-grained resolution for object features alongside normal visual
sensitivity to the segregation between objects. The findings are also discussed
in reference to the distinction made in earlier studies between visual short-term
memory and iconic memory.
PMID- 25112395
TI - Time-based event expectations employ relative, not absolute, representations of
time.
AB - When the timing of an event is predictable, humans automatically form implicit
time-based event expectations. We investigated whether these expectations rely on
absolute (e.g., 800 ms) or relative (e.g., a shorter duration) representations of
time. In a choice-response task with two different pre-target intervals,
participants implicitly learned that targets were predictable by interval
durations. In a test phase, the two intervals were either considerably shortened
or lengthened. In both cases, behavioral tendencies transferred from practice to
test according to relative, not absolute, interval duration. We conclude that
humans employ relative representations of time periods when forming time-based
event expectations. These results suggest that learned time-based event
expectations (e.g., in communication and human-machine interaction) should
transfer to faster or slower environments if the relative temporal distribution
of events is preserved.
PMID- 25112396
TI - Interim FDG PET scans in lymphoma: SUV measurement error may impair qPET
methodology.
PMID- 25112397
TI - Sources of variability in FDG PET imaging and the qPET value: reply to Laffon and
Marthan.
PMID- 25112398
TI - Targeting post-infarct inflammation by PET imaging: comparison of (68)Ga-citrate
and (68)Ga-DOTATATE with (18)F-FDG in a mouse model.
AB - Imaging of inflammation early after myocardial infarction (MI) is a promising
approach to the guidance of novel molecular interventions that support endogenous
healing processes. (18)F-FDG PET has been used, but may be complicated by
physiological myocyte uptake. We evaluated the potential of two alternative
imaging targets: lactoferrin binding by (68)Ga-citrate and somatostatin receptor
binding by (68)Ga-DOTATATE. METHODS: C57Bl/6 mice underwent permanent coronary
artery ligation. Serial PET imaging was performed 3 - 7 days after MI using
(68)Ga-citrate, (68)Ga-DOTATATE, or (18)F-FDG with ketamine/xylazine suppression
of myocyte glucose uptake. Myocardial perfusion was evaluated by (13)N-ammonia
PET and cardiac geometry by contrast-enhanced ECG-gated CT. RESULTS: Mice
exhibited a perfusion defect of 30 - 40% (of the total left ventricle) with
apical anterolateral wall akinesia and thinning on day 7 after MI. (18)F-FDG with
ketamine/xylazine suppression demonstrated distinct uptake in the infarct region,
as well as in the border zone and remote myocardium. The myocardial standardized
uptake value in MI mice was significantly higher than in healthy mice under
ketamine/xylazine anaesthesia (1.9 +/- 0.4 vs. 1.0 +/- 0.1). (68)Ga images
exhibited high blood pool activity with no specific myocardial uptake up to 90
min after injection (tissue-to-blood contrast 0.9). (68)Ga-DOTATATE was rapidly
cleared from the blood, but myocardial SUV was very low (0.10 +/- 0.03).
CONCLUSION: Neither (68)Ga nor (68)Ga-DOTATATE is a useful alternative to (18)F
FDG for PET imaging of myocardial inflammation after MI in mice. Among the three
tested approaches, (18)F-FDG with ketamine/xylazine suppression of cardiomyocyte
uptake remains the most practical imaging marker of post-infarct inflammation.
PMID- 25112400
TI - [Dementia in families with a Turkish migration background. Organization and
characteristics of domestic care arrangements].
AB - BACKROUND: Until recently public health and health services research has not been
concerned with people suffering from dementia with a Turkish migration background
as a priority. There is little evidence about the situation of this population;
however, it is known that these individuals almost always live with their
families and are cared for by their families generally without seeking
professional support. The aim of this study was to gain insight into the
organization and characteristics of home-based care arrangements for people
suffering from dementia with a Turkish migration background from the family
carer's perspective. METHODS: Interviews with seven family carers. The principles
of the grounded theory served as a framework for data analysis. RESULTS:
Unconditional commitment to caring for a family member with dementia was
identified as the main characteristic of care arrangements in families with a
Turkish migration background. Dementia is not a factor that has an impact on the
decision of families to assume care responsibility for an affected family member
and there is a lack of knowledge about dementia in general. There are various
inhibiting factors for the utilization of formal services and the family carers
in this sample complained that the available services are not culturally
sensitive. CONCLUSION: There seems to be an extensive need for information and
counselling regarding care dependency and dementia among the Turkish community.
To provide personal-centred care and relief to these families in the future,
efforts should be made to adapt the current care system to the specific needs and
demands of this population. Cultural sensitivity in general and individual
subjective needs of persons with a Turkish migration background affected by
dementia should be taken into account.
PMID- 25112399
TI - Diagnostic accuracy of whole-body PET/MRI and whole-body PET/CT for TNM staging
in oncology.
AB - PURPOSE: In various tumours PET/CT with [(18)F]FDG is widely accepted as the
diagnostic standard of care. The purpose of this study was to compare a dedicated
[(18)F]FDG PET/MRI protocol with [(18)F]FDG PET/CT for TNM staging in a cohort of
oncological patients. METHODS: A dedicated [(18)F]FDG PET/MRI protocol was
performed in 73 consecutive patients (mean age of 59 years, range 21 - 85 years)
with different histologically confirmed solid primary malignant tumours after a
routine clinical FDG PET/CT scan (60 min after injection of 295 +/- 45 MBq
[(18)F]FDG). TNM staging according to the 7th edition of the AJCC Cancer Staging
Manual was performed by two readers in separate sessions for PET/CT and PET/MRI
images. Assessment of the primary tumour and nodal and distant metastases with
FDG PET/CT and FDG PET/MRI was based on qualitative and quantitative analyses.
Histopathology, and radiological and clinical follow-up served as the standards
of reference. A McNemar test was performed to evaluate the differences in
diagnostic performance between the imaging procedures. RESULTS: From FDG PET/CT
and FDG PET/MRI T stage was correctly determined in 22 (82 %) and 20 (74 %) of 27
patients, N stage in 55 (82 %) and 56 (84 %) of 67 patients, and M stage in 32
(76 %) and 35 (83 %) of 42 patients, respectively. Sensitivity, specificity,
positive predictive value, negative predictive value and diagnostic accuracy for
lymph node metastases were 65 %, 94 %, 79 %, 89 % and 87 % for PET/CT, and 63 %,
94 %, 80 %, 87 % and 85 % for PET/MRI. The respective values for the detection of
distant metastases were 50 %, 82 %, 40 %, 88 % and 76 % for PET/CT, and 50 %, 91
%, 57 %, 89 % and 83 % for PET/MRI. Differences between the two imaging
modalities were not statistically significant (P > 0.05). CONCLUSION: According
to our results, FDG PET/CT and FDG PET/MRI are of equal diagnostic accuracy for
TNM staging in patients with solid tumours.
PMID- 25112401
TI - ["So I would have been sitting at home and moping...": How do older single people
in need of support experience companionship by volunteers after discharge from
hospital?].
AB - BACKGROUND: Despite the well-known link between social support and health as well
as quality of life only a few scientifically meaningful studies have been carried
out to actively promote social support. In the +P Project (post-hospital lay
support for patients) elderly people in need of support after a stay in hospital
are accompanied in their daily life by volunteers. The qualitative research part
in the study evaluates conditions which led to the adoption of the support by the
volunteers and how the elderly people experienced this companionship. METHODS:
The analysis followed the grounded theory method. In a theoretical sampling nine
accompanied people were identified and participated in narrative interviews
regarding their experience of the voluntary support. RESULTS: In addition to
personality traits of the elderly and perceived seriousness of the project the
interpersonal relationship was important for the adoption of the companionship.
Key factors were the perceived similarity between the older people and their
supporters as well as confidence in the volunteers and their skills. The support
contributed to facilitating and enriching the daily life of the elderly and even
friendships with the volunteers developed. CONCLUSIONS: The results indicate that
volunteers can help to compensate a lack of social support for the elderly. The
results confirm theoretical models of coping with age and disease-related losses
and models of social relations in old age. At the same time this study underpins
political recommendations to strengthen community engagement to promote social
networks for older people.
PMID- 25112402
TI - Multimodal sensor-based fall detection within the domestic environment of elderly
people.
AB - BACKGROUND: Falls represent a major threat to the health of the elderly and are a
growing burden on the healthcare systems. With the growth of the elderly
population within most societies efficient fall detection becomes increasingly
important; however, existing fall detection systems still fail to produce
reliable results. OBJECTIVES: A study was carried out on sensor-based fall
detection, analysis of falls with the help of fall protocols and the analysis of
user acceptance of fall detection sensor technology through questionnaires.
MATERIAL AND METHODS: A total of 28 senior citizens were recruited from a German
community-dwelling population. The primary goal was a sensor-based detection of
falls with accelerometers, video cameras and microphones. Details of the falls
were analyzed with the help of medical geriatric assessments and standardized
fall protocols. The study duration was 8 weeks and required a maximum of nine
visits per subject. RESULTS: The study participants were 28 subjects with a mean
age of 74.3 and a standard deviation (SD) of +/- 6.3 years of which 12 were male
and 16 female. A total of 1225.7 measurement days were recorded from all
participants and the algorithms detected 2.66 falls per day. During the study
period 15 falls occurred and 12 of these falls were correctly recognized by the
fall detection system. CONCLUSION: Current fall detection technologies work well
under laboratory conditions but it is still problematic to produce reliable
results when these technologies are applied to real life conditions. Acceptance
towards the sensors decreased after study participation although the system was
generally perceived as useful or very useful.
PMID- 25112403
TI - Lysyl oxidase rs1800449 polymorphism and cancer risk among Asians: evidence from
a meta-analysis and a case-control study of colorectal cancer.
AB - Growing evidence has indicated that lysyl oxidase (LOX) G473A polymorphism
(rs1800449) is associated with cancer risk among Asians. However, results of
single center and small sample study lack enough power. We first investigated the
effect of LOX G473A polymorphism on cancer risk among Asians by a meta-analysis,
and then further validated this association by a case-control study of colorectal
cancer (CRC) with LOX G473A polymorphism in a Chinese population. STATA 12.0
software was used for the meta-analysis. The relationships were evaluated by
calculating the pooled odds ratios (ORs) and their 95 % confidence intervals
(CIs). In a case-control study comprising 577 CRC patients and 696 controls, LOX
G473A polymorphism was detected by polymerase chain reaction-restriction fragment
length polymorphism (PCR-RFLP) method. Logistic regression was used to evaluate
genetic associations with the occurrence of CRC. The results of our meta
analysis, including seven case-control studies with a total of 2,377 cancer
patients and 2,499 controls, suggested that LOX G473A polymorphism might be
associated with an increased risk of cancer among Asians. In addition, results of
a case-control study indicated that individuals with the AA or AG genotype had a
significantly increased susceptibility to CRC occurrence, compared with
individuals who had GG genotype. Overall, this meta-analysis and case-control
study of CRC observed convincing association of LOX G473A polymorphism with
cancer risk in Asians; our study would contribute to complete elucidation of
carcinogenesis.
PMID- 25112406
TI - Malignant transformation of craniopharyngioma with detailed follow-up.
AB - A 29-year-old male patient was admitted into hospital with the main complaint of
progressive visual disturbance. Both CT SCAN and MRI demonstrated a cystic-solid
contrast-enhancing sellar-suprasellar mass with obvious calcification.
Histopathological examination of the first resected specimen showed a typical
appearance of adamantinomatous craniopharyngioma. The patient received gamma
knife therapy after his first operation because of partial tumor removal. He
experienced two relapses in the subsequent 2 years, for which only surgical
resection was performed. The later histopathology presented malignant appearance
with tumor cells moderate to severe pleomorphism, hyperchromasia, increased
nuclear cytoplastic ratio, high mitotic activity (30/10 high power fields) and
focal coagulative necrosis. The patient died 9 months after identification of
histologic malignancy. Clinical and histopathological features, biological
behavior of one case of malignant craniopharyngioma were discussed, with a brief
review of the relevant literature.
PMID- 25112407
TI - Effect of aqueous leaf extract of Dalbergia sissoo Roxb. on spermatogenesis and
fertility in male mice.
AB - OBJECTIVES: Antifertility effects of Dalbergia sissoo in male mice were
investigated. METHODS: Adult Parkes strain male mice were orally administered
aqueous leaf extract of Dalbergia sissoo (50 and 100 mg/kg body weight/day) or
distilled water or no treatment (controls) for 35 days (n = 5/group). Motility,
viability and number of spermatozoa in the cauda epididymidis; testis histology;
serum level of testosterone; and toxicological parameters were evaluated. To
assess reversibility, more mice were treated with 100 mg/kg body weight of
Dalbergia sissoo or distilled water (n = 5/group) for 35 days and sacrificed 56
days later. Fertility was also assessed separately. RESULTS: Histologically,
testes of Dalbergia-treated mice showed dissimilar degenerative changes in the
seminiferous tubules. Significant reductions were noted (i) in epididymal sperm
motility, viability and number, and (ii) in serum level of testosterone in
Dalbergia-treated mice compared to controls. However, serum levels of alanine
aminotransferase, aspartate aminotransferase and creatinine, and haematological
parameters were not affected. Also libido of Dalbergia-treated males showed no
change, but their fertility was markedly suppressed. By 56 days of treatment
withdrawal, alterations induced in the above parameters returned to control
levels. CONCLUSIONS: Dalbergia sissoo treatment caused reversible suppression of
spermatogenesis and fertility in P mice, without eliciting detectable toxic
effects.
PMID- 25112405
TI - Mucosal vaccine delivery by non-recombinant spores of Bacillus subtilis.
AB - Development of mucosal vaccines strongly relies on an efficient delivery system
and, over the years, a variety of approaches based on phages, bacteria or
synthetic nanoparticles have been proposed to display and deliver antigens. The
spore of Bacillus subtilis displaying heterologous antigens has also been
considered as a mucosal vaccine vehicle, and shown able to conjugate some
advantages of live microrganisms with some of synthetic nanoparticles. Here we
review the use of non-recombinant spores of B. subtilis as a delivery system for
mucosal immunizations. The non-recombinant display is based on the adsorption of
heterologous molecules on the spore surface without the need of genetic
manipulations, thus avoiding all concerns about the use and environmental release
of genetically modified microorganisms. In addition, adsorbed molecules are
stabilized and protected by the interaction with the spore, suggesting that this
system could reduce the rapid degradation of the antigen, often observed with
other delivery systems and identified as a major drawback of mucosal vaccines.
PMID- 25112408
TI - Prognostic role of CD44 expression in osteosarcoma: evidence from six studies.
AB - BACKGROUND: Numerous studies examining the relationship between CD44 expression
and prognostic impact in patients with osteosarcoma have yielded inconclusive
results. The aim of this meta-analysis was carried out to investigate the
relationship between CD44 expression and the survival in patients with
osteosarcoma. METHODS: We therefore conducted a meta-analysis to provide a
comprehensive evaluation of the prognostic role of CD44 expression on the overall
survival rate and metastasis, which compared the positive and negative expression
of CD44 in patients of the available studies. RESULTS: A detailed search was made
in MEDLINE and EMBASE for relevant original articles published in English.
Finally, a total of six studies with 329 osteosarcoma patients were involved to
estimate the relationship between CD44 expression and metastasis of tumor and
overall survival. Positive expressions of CD44 did not predict neoplasm
metastasis (RR = 1.36, 95% CI: 1.00-1.84, P = 0.50), and the results indicated
that higher expression of CD44 could not predict poorer survival in osteosarcoma
with the pooled HR of 0.55 (95% CI: 0.27-1.13, P = 0.47). CONCLUSIONS: The
findings from this present meta-analysis suggest that CD44 expression is not
associated with overall survival rate and metastasis in osteosarcoma. VIRTUAL
SLIDES: The virtual slide(s) for this article can be found here:
http://www.diagnosticpathology.diagnomx.eu/vs/1373995521295618.
PMID- 25112409
TI - Gaps in preparedness of clergy and healthcare providers to address mental health
needs of returning service members.
AB - To elucidate gaps in the preparedness of clergy and healthcare providers to care
for service members (SM) with deployment-related mental health needs.
Participants identified clinically relevant symptoms in a standardized video role
play of a veteran with deployment-related mental health needs and discussed their
preparedness to deal with SM. Clergy members identified suicide and depression
most often, while providers identified difficulty sleeping, low energy,
nightmares and irritability. Neither clergy nor providers felt prepared to
minister to or treat SM with traumatic brain injury. Through a mixed methods
approach, we identified gaps in preparedness of clergy and healthcare providers
in dealing with the mental health needs of SM.
PMID- 25112411
TI - Low drain fluid amylase predicts absence of pancreatic fistula following
pancreatectomy.
AB - INTRODUCTION: Improvements in the ability to predict pancreatic fistula could
enhance patient outcomes. Previous studies demonstrate that drain fluid amylase
on postoperative day 1 (DFA1) is predictive of pancreatic fistula. We sought to
assess the accuracy of DFA1 and to identify a reliable DFA1 threshold under which
pancreatic fistula is ruled out. METHODS: Patients undergoing pancreatic
resection from November 1, 2011 to December 31, 2012 were selected from the
American College of Surgeons-National Surgical Quality Improvement Program
Pancreatectomy Demonstration Project database. Pancreatic fistula was defined as
drainage of amylase-rich fluid with drain continuation >7 days, percutaneous
drainage, or reoperation for a pancreatic fluid collection. Univariate and multi
variable regression models were utilized to identify factors predictive of
pancreatic fistula. RESULTS: DFA1 was recorded in 536 of 2,805 patients who
underwent pancreatic resection, including pancreaticoduodenectomy (n = 380),
distal pancreatectomy (n = 140), and enucleation (n = 16). Pancreatic fistula
occurred in 92/536 (17.2%) patients. DFA1, increased body mass index, small
pancreatic duct size, and soft texture were associated with fistula (p < 0.05). A
DFA1 cutoff value of <90 U/L demonstrated the highest negative predictive value
of 98.2%. Receiver operating characteristic (ROC) curve confirmed the predictive
relationship of DFA1 and pancreatic fistula. CONCLUSION: Low DFA1 predicts the
absence of a pancreatic fistula. In patients with DFA1 < 90 U/L, early drain
removal is advisable.
PMID- 25112412
TI - Reliability and validity of the Finnish version of the American Shoulder and
Elbow Surgeons Standardized Shoulder Assessment Form, patient self-report
section.
AB - BACKGROUND: The American Shoulder and Elbow Surgeons Standardized Shoulder
Assessment Form (ASES) is one of the most widely used shoulder outcome tools in
clinical work and in scientific studies. However, it has not been validated in
the Finnish language. The aims of this study were to cross-culturally adapt the
ASES to the Finnish language and to study the psychometric properties of the self
report section of the ASES. METHODS: A total of 105 patients with shoulder
symptoms answered the questionnaires of the ASES, a single disability question,
the Simple Shoulder Test (SST), and the Short-Form 36 Health Survey (SF-36). The
reliability of the ASES questionnaire was studied using a test-retest procedure
at 2-week intervals. Psychometric assessment was performed by testing the
construct validity, internal consistency, the criterion validity, and the
convergent validity of the ASES. RESULTS: The reproducibility and internal
consistency of the ASES were 0.83 (95% CI 0.70 to 0.90) and 0.88 (95% Cl 0.84 to
0.91). There were no significant differences between the diagnostic groups in the
pain scores from the ASES, and the function score was significantly higher in the
instability group compared to the other groups. The convergent validity of the
ASES correlated with the SST, r = 0.73 (p < 0.001); the single disability
question, r = -0.74 (p < 0.001); and the Physical Component Score of the SF-36, r
= 0.57 (p < 0.001). CONCLUSIONS: The Finnish version of the ASES proved to be a
reliable and valid tool for assessing shoulder disabilities in patients with
different shoulder diagnoses, including rotator cuff disease, instability, and
osteoarthritis.
PMID- 25112410
TI - Lithium chloride therapy fails to improve motor function in a transgenic mouse
model of Machado-Joseph disease.
AB - The accumulation of misfolded proteins in neurons, leading to the formation of
cytoplasmic and nuclear aggregates, is a common theme in age-related
neurodegenerative diseases, possibly due to disturbances of the proteostasis and
insufficient activity of cellular protein clearance pathways. Lithium is a well
known autophagy inducer that exerts neuroprotective effects in different
conditions and has been proposed as a promising therapeutic agent for several
neurodegenerative diseases. We tested the efficacy of chronic lithium (10.4
mg/kg) treatment in a transgenic mouse model of Machado-Joseph disease, an
inherited neurodegenerative disease, caused by an expansion of a polyglutamine
tract within the protein ataxin-3. A battery of behavioral tests was used to
assess disease progression. In spite of activating autophagy, as suggested by the
increased levels of Beclin-1, Atg7, and LC3-II, and a reduction in the p62
protein levels, lithium administration showed no overall beneficial effects in
this model concerning motor performance, showing a positive impact only in the
reduction of tremors at 24 weeks of age. Our results do not support lithium
chronic treatment as a promising strategy for the treatment of Machado-Joseph
disease (MJD).
PMID- 25112414
TI - Developmental prosopagnosia referred to outpatient psychiatric service.
PMID- 25112413
TI - Renal function assessment in child and adolescent heart transplant recipients
during routine cardiac catheterization.
AB - CKD identification after pediatric heart transplantation (PHT) is limited by
inaccuracies in estimates of GFR. We hypothesized that GFR can be measured by a
modified iohexol clearance protocol in PHT recipients and that the CKiD formula
provides a better estimate of GFR than other estimating equations. A cross
sectional study of PHT recipients, ages 2-18 yr, undergoing coronary angiography
was undertaken. The angiography dose of iohexol was divided by the area under the
curve from three iohexol levels post-infusion to calculate GFR. Agreement between
iGFR and multiple estimating equations (eGFR) was assessed. In 31 subjects,
median age was 15.0 yr (IQR 7.6, 16.6). Mean iGFR was 93.8 (s.d. 22.5)
mL/min/1.73 m(2) ; 16 (52%) had an iGFR <90 mL/min/1.73 m(2) . The full CKiD
formula (mean eGFR 88.9, s.d. 14.9) had low bias (-5.0), narrowest 95% limits of
agreement (-42.0, 32.1), highest 30% (94%) and 10% (52%) accuracy, and highest
correlation coefficient (0.576) relative to iGFR. We describe a novel modified
iohexol clearance method to assess GFR after PHT. Over half of the cohort had an
iGFR <90, suggesting CKD. The full CKiD formula performs best with respect to
bias, accuracy, and correlation.
PMID- 25112415
TI - Low levels of 25-hydroxy vitamin D and active 1,25-dihydroxyvitamin D
independently associated with type 2 diabetes mellitus in older Australian men:
the Concord Health and Ageing in Men Project.
AB - OBJECTIVES: To examine the associations between serum 25-hydroxyvitamin D (25OHD)
levels and the active vitamin D metabolite, 1,25-hydroxyvitamin D (1,25OHD), with
type 2 diabetes mellitus (DM) in community-living men aged 70 and older. DESIGN:
Cross-sectional. SETTING: A population-based, cross-sectional analysis of the
baseline phase of the Concord Health and Ageing in Men Project (CHAMP), a large
epidemiological study conducted in Sydney between January 2005 and May 2007.
PARTICIPANTS: Community dwelling men aged 70 and older taking part in CHAMP (N =
1,659). MEASUREMENTS: Serum 25OHD and 1,25OHD levels, presence of DM, age,
country of birth, season of blood collection, sun exposure, body mass index,
vitamin D supplement use, statin use, income, measures of health, depression,
activity of daily living disabilities, parathyroid hormone, estimated glomerular
filtration rate, phosphate, and calcium. RESULTS: The prevalence of DM was 20.0%.
There was a significant association between low 25OHD and 1,25OHD levels and DM
that remained after adjustment for a wide range of confounders and covariates of
clinical significance such as comorbidity, renal function, calciotropic hormones,
and medications. CONCLUSION: 25OHD and 1,25OHD levels were associated with DM.
The independent association between serum 25OHD and 1,25OHD concentrations and DM
raises the question of whether each of the two vitamin D metabolites may
influence DM through different biological mechanisms and pathways.
PMID- 25112416
TI - A drastic substituent effect on the emission properties of quinone diimine models
and valuable insight into the excited states of emeraldine.
AB - The (alpha-NR,alpha'-NR,N,N'-(C6H4C=CSiMe3)4)[Q] models ([Q] = -N=C6H4=N-)
exhibit upper excited state emissions Sn,Tn -> S0 (n >1, R = Boc), similar to
emeraldine, vs. a fluorescence S1 -> S0 (R = H), driven by a large change in
dihedral angles made by the NR-C6H4 and [Q] planes and intramolecular H-bonds.
PMID- 25112417
TI - Hepatitis mouse models: from acute-to-chronic autoimmune hepatitis.
AB - Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated
with interface hepatitis, raised plasma liver enzymes, the presence of
autoantibodies and regulatory T-cell (Tregs) dysfunction. The clinical course is
heterogeneous, manifested by a fulminant or indolent course. Although genetic
predisposition is well accepted, the combination with currently undefined
environmental factors is crucial for the development of the disease. Progress in
the development of reliable animal models provides added understanding of the
pathophysiology of AIH, and these will be very useful in evaluating potential
therapeutics. It appears that artificially breaking tolerance in the liver is
easy. However, maintaining this state of tolerance breakdown, to get chronic
hepatitis, is difficult because liver immune homeostasis is strongly regulated by
several immune response inhibitory mechanisms. For example, Tregs are crucial
regulators in acute and chronic hepatitis, and C57BL/6 mice are most prone to
experimental AIH. Immunization of C57BL/6 mice with liver (AIH) autoantigens
(CYP2D6/FTCD or IL-4R) and the disturbance of liver regulatory mechanism(s),
leading to experimental AIH, are likely to be most representative of human AIH
pathology.
PMID- 25112420
TI - Cardiopulmonary and anesthetic effects of the combination of butorphanol,
midazolam and alfaxalone in Beagle dogs.
AB - OBJECTIVE: To evaluate the physiological variables, arterial blood gas values,
induction of anesthesia quality, and recovery quality using the combination of
butorphanol, midazolam and alfaxalone in dogs. ANIMALS: Ten healthy adult Beagle
dogs weighing 8.3 +/- 3.1 kg. METHODS: Rectal temperature (T), pulse rate (PR),
respiratory rate (f(R)), mean arterial pressure (MAP), and arterial blood gases
were measured and recorded prior to intravenous (IV) administration of
butorphanol, prior to administration of both midazolam and alfaxalone IV 10
minutes later, then every 5 minutes for 20 minutes. M-mode echocardiographic left
ventricular (LV) indices were measured before and 5 minutes after administration
of alfaxalone. Qualitative scores for induction of anesthesia and recovery were
allocated, duration of anesthesia and recovery were calculated, and adverse
events were recorded. RESULTS: Scores for induction and recovery quality were
excellent. No significant adverse events were observed. Mean +/- SD time from
induction to extubation and to standing (full recovery) was 29 +/- 6 and 36 +/- 8
minutes, respectively. There were statistically significant changes in PR, f(R)
and MAP after drug administration. Transient hypercarbia developed after
alfaxalone injection. The echocardiographic LV indices were reduced after
alfaxalone injection, although those changes were not statistically significant.
CONCLUSIONS AND CLINICAL RELEVANCE: The combination of butorphanol, midazolam and
alfaxalone provided excellent quality of induction of anesthesia and exerted
minimal cardiopulmonary effects in healthy dogs.
PMID- 25112419
TI - Structural and morphometric comparison of the molar teeth in pre-eruptive
developmental stage of PACAP-deficient and wild-type mice.
AB - Pituitary adenylate cyclase activating polypeptide (PACAP) is a pleiotropic
neuropeptide with widespread distribution. It plays pivotal role in neuronal
development. PACAP-immunoreactive fibers have been found in the tooth pulp, and
recently, it has been shown that PACAP may also play a role in the regeneration
of the periodontium after luxation injuries. However, there is no data about the
effect of endogenous PACAP on tooth development. Ectodermal organogenesis
including tooth development is regulated by different members of bone
morphogenetic protein (BMP), fibroblast growth factor (FGF), hedgehog (HH), and
Wnt families. There is also a growing evidence to support the hypothesis that
PACAP interacts with sonic hedgehog (SHH) receptor (PTCH1) and its downstream
target (Gli1) suggesting its role in tooth development. Therefore, our aim was to
study molar tooth development in mice lacking endogenous PACAP. In this study
morphometric, immunohistochemical and structural comparison of molar teeth in pre
eruptive developmental stage was performed on histological sections of 7-day-old
wild-type and PACAP-deficient mice. Further structural analysis was carried out
with Raman microscope. The morphometric comparison of the 7-day-old samples
revealed that the dentin was significantly thinner in the molars of PACAP
deficient mice compared to wild-type animals. Raman spectra of the enamel in wild
type mice demonstrated higher diversity in secondary structure of enamel
proteins. In the dentin of PACAP-deficient mice higher intracrystalline
disordering in the hydroxyapatite molecular structure was found. We also obtained
altered SHH, PTCH1 and Gli1 expression level in secretory ameloblasts of PACAP
deficient mice compared to wild-type littermates suggesting that PACAP might play
an important role in molar tooth development and matrix mineralization involving
influence on SHH signaling cascade.
PMID- 25112421
TI - Development of an ELISA microarray assay for the sensitive and simultaneous
detection of ten biodefense toxins.
AB - Plant and microbial toxins are considered bioterrorism threat agents because of
their extreme toxicity and/or ease of availability. Additionally, some of these
toxins are increasingly responsible for accidental food poisonings. The current
study utilized an ELISA-based protein antibody microarray for the multiplexed
detection of ten biothreat toxins, botulinum neurotoxins (BoNT) A, B, C, D, E, F,
ricin, shiga toxins 1 and 2 (Stx), and staphylococcus enterotoxin B (SEB), in
buffer and complex biological matrices. The multiplexed assay displayed a
sensitivity of 1.3 pg mL(-1) (BoNT/A, BoNT/B, SEB, Stx-1 and Stx-2), 3.3 pg mL(
1) (BoNT/C, BoNT/E, BoNT/F) and 8.2 pg mL(-1) (BoNT/D, ricin). All assays
demonstrated high accuracy (75-120 percent recovery) and reproducibility (most
coefficients of variation <20%). Quantification curves for the ten toxins were
also evaluated in clinical samples (serum, plasma, nasal fluid, saliva, stool,
and urine) and environmental samples (apple juice, milk and baby food) with
overall minimal matrix effects. The multiplex assays were highly specific, with
little cross-reactivity observed between the selected toxin antibodies. The
results demonstrate a multiplex microarray that improves current immunoassay
sensitivity for biological warfare agents in buffer, clinical, and environmental
samples.
PMID- 25112418
TI - Pituitary adenylate cyclase-activating polypeptide (PACAP) signalling enhances
osteogenesis in UMR-106 cell line.
AB - Presence of the pituitary adenylate cyclase-activating polypeptide (PACAP)
signalling has been proved in various peripheral tissues. PACAP can activate
protein kinase A (PKA) signalling via binding to pituitary adenylate cyclase
activating polypeptide type I receptor (PAC1), vasoactive intestinal polypeptide
receptor (VPAC) 1 or VPAC2 receptor. Since little is known about the role of this
regulatory mechanism in bone formation, we aimed to investigate the effect of
PACAP on osteogenesis of UMR-106 cells. PACAP 1-38 as an agonist and PACAP 6-38
as an antagonist of PAC1 were added to the culture medium. Surprisingly, both
substances enhanced protein expressions of collagen type I, osterix and alkaline
phosphatase, along with higher cell proliferation rate and an augmented
mineralisation. Although expression of PKA was elevated, no alterations were
detected in the expression, phosphorylation and nuclear presence of CREB, but
increased nuclear appearance of Runx2, the key transcription factor of osteoblast
differentiation, was shown. Both PACAPs increased the expressions of bone
morphogenetic proteins (BMPs) 2, 4, 6, 7 and Smad1 proteins, as well as that of
Sonic hedgehog, PATCH1 and Gli1. Data of our experiments indicate that activation
of PACAP pathway enhances bone formation of UMR-106 cells and PKA, BMP and
Hedgehog signalling pathways became activated. We also found that PACAP 6-38 did
not act as an antagonist of PACAP signalling in UMR-106 cells.
PMID- 25112423
TI - Speech-language pathology practices with Indigenous Australians with acquired
communication disorders.
AB - PURPOSE: Little is known about the needs of Indigenous Australian adults with
acquired communication disorders (ACD) following stroke or brain injury and how
these needs are met by speech-language pathology (SLP) services. In order for the
profession to respond to the challenges of providing culturally appropriate, well
tailored and accessible services, more information on current practice and SLPs'
concerns and attitudes is required. METHOD: This paper reports on a national
survey with completed responses from 112 SLPs, who worked with adult neurological
populations, about their levels of contact with Indigenous clients, cultural
competency training and potential sources of support. RESULT. Of the total
respondents, 63 SLPs reported clinical contact with Indigenous clients and :they
also answered questions on their assessment, intervention and discharge
practices; liaison with family; and involvement with Aboriginal Health
Professionals and interpreters. This group reported insufficient knowledge about
Indigenous culture, lack of support and lower levels of confidence overall in
working with these clients as compared to non-Indigenous clients. They wanted
more flexible services for their Indigenous clients, good access to interpreters
and culturally appropriate assessments and treatments delivered in culturally
appropriate settings. CONCLUSION: This research provides a useful starting point
towards understanding SLPs' perspectives and practice at a national level.
PMID- 25112425
TI - A new titanosauriform sauropod (Dinosauria: Saurischia) from the Lower Cretaceous
of Hyogo, Japan.
AB - A new genus and species of titanosauriform sauropod is erected based on a partial
skeleton found in the Lower Cretaceous Sasayama Group of Hyogo Prefecture, SW
Japan. The new taxon is here named as Tambatitanis amicitiae gen. et sp. nov.,
which is diagnosed by the following features of the caudal vertebrae, chevrons
and braincase: the postzygapophysis and the summit of the neural spine of the
anterior caudal vertebrae are located beyond the posterior border of the centrum,
the spine of the anterior caudal vertebrae is curved strongly anteriorly and bow
shaped in lateral view, the summit of the neural spine is expanded and
hemispherical with its anterior face excavated by the posterodorsal extension of
a deep and narrow SPRF, the transverse process of the anterior caudal vertebrae
are short and L shaped, the anterior chevron is the longest among sauropods in
proportion to body size, the distal ends of the anterior chevrons are rod-shaped,
the distal ends of the mid chevrons are transversely thin and anteroposteriorly
long without cranial processes, and the dorsal border of the shaft of the
paroccipital process that forms the ventral margin of the posttemporal fenestra
is short mediolaterally and V-shaped in posterior view. A phylogenetic analysis
suggests that T. amicitiae is a basal titanosauriform, possibly belonging to the
East Asian endemic clade Euhelopodidae. The caudals and chevrons are described in
detail in order to document highly autapomorphic features of the new taxon as
well as potentially phylogenetically informative characters. The discovery of T.
amicitiae suggests that East Asian basal titanosauriforms were diverse not only
in the number of the taxa but also in the morphological variation of the caudal
elements.
PMID- 25112426
TI - Systematics, morphology, and ecological history of the Mascarene starlings (Aves:
Sturnidae) with the description of a new genus and species from Mauritius.
AB - Two endemic starlings, both extinct, have been described from the Mascarene
Islands of Reunion and Rodrigues: the Hoopoe Starling, Huppe or Reunion Crested
Starling Fregilupus varius, which is known from 19 skins and a single Holocene
proximal end of a fossil femur, and the Rodrigues Starling Necropsar rodericanus,
which is known as specimens only from fossils of most skeletal elements. Both
were recorded alive in early accounts of Mascarene faunas. A third species of
starling Cryptopsar ischyrhynchus gen. nov. sp. nov. is described herein from
fossils from Mauritius, but was never reported in the early literature. This
paper provides an analysis of the Sturnidae of the Mascarene Islands based on
newly discovered fossil remains, and details historical reports and accounts.
Their ecology and extinction are interpreted from historical evidence. Necropsar,
Cryptopsar and Fregilupus clearly form part of the same clade, but morphological
analysis shows that Necropsar and Cryptopsar are more closely related to each
other than to Fregilupus and may have been part of a different colonisation
event. All three genera appear to have their origins in SE Asia and have
morphological similarities with the SE Asian sturnid genera, Sturnia and
Gracupica, so they presumably colonised the islands via island-hopping during
lower sea level stands.
PMID- 25112424
TI - Molecular characterization of the thioredoxin system from Methanosarcina
acetivorans.
AB - The thioredoxin system, composed of thioredoxin reductase (TrxR) and thioredoxin
(Trx), is widely distributed in nature, where it serves key roles in electron
transfer and in the defense against oxidative stress. Although recent evidence
reveals Trx homologues are almost universally present among the methane-producing
archaea (methanogens), a complete thioredoxin system has not been characterized
from any methanogen. We examined the phylogeny of Trx homologues among
methanogens and characterized the thioredoxin system from Methanosarcina
acetivorans. Phylogenetic analysis of Trx homologues from methanogens revealed
eight clades, with one clade containing Trxs broadly distributed among
methanogens. The Methanococci and Methanobacteria each contain one additional Trx
from another clade, respectively, whereas the Methanomicrobia contain an
additional five distinct Trxs. Methanosarcina acetivorans, a member of the
Methanomicrobia, contains a single TrxR (MaTrxR) and seven Trx homologues (MaTrx1
7), with representatives from five of the methanogen Trx clades. Purified
recombinant MaTrxR had 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) reductase and
oxidase activities. The apparent Km value for NADPH was 115-fold lower than that
for NADH, consistent with NADPH as the physiological electron donor to MaTrxR.
Purified recombinant MaTrx2, MaTrx6 and MaTrx7 exhibited dithiothreitol- and
lipoamide-dependent insulin disulfide reductase activities. However, only MaTrx7,
which is encoded adjacent to MaTrxR, could serve as a redox partner to MaTrxR.
These results reveal that M. acetivorans harbors at least three functional and
distinct Trxs, and a complete thioredoxin system composed of NADPH, MaTrxR and at
least MaTrx7. This is the first characterization of a complete thioredoxin system
from a methanogen, which provides a foundation to understand the system in
methanogens.
PMID- 25112427
TI - Revision of the Oriental genus Horniella Raffray (Coleoptera, Staphylinidae,
Pselaphinae).
AB - The Oriental pselaphine genus Horniella Raffray, 1905 (tribe Tyrini: subtribe
Somatipionina) is redefined and revised. Twenty-five new species are described:
H. centralis Yin & Li, sp. n., H. confragosa Yin & Li, sp. n., H. dao Yin & Li,
sp. n., H. hongkongensis Yin & Li, sp. n., H. nakhi Yin & Li, sp. n., H.
schuelkei Yin & Li, sp. n., H. sichuanica Yin & Li, sp. n., H. simplaria Yin &
Li, sp. n., and H. tianmuensis Yin & Li, sp. n. from China, H. himalayica Yin &
Li, sp. n. from Nepal and North India, H. asymmetrica Yin & Li, sp. n., H.
burckhardti Yin & Li, sp. n., H. intricata Yin & Li, sp. n., H. kaengkrachan Yin
& Li, sp. n., H. khaosabap Yin & Li, sp. n., H. loebli Yin & Li, sp. n., H.
phuphaman Yin & Li, sp. n., H. prolixo Yin & Li, sp. n., and H. schwendingeri Yin
& Li, sp. n. from Thailand, H. philippina Yin & Li, sp. n. from the Philippines,
H. awana Yin & Li, sp. n., H. gigas Yin & Li, sp. n., H. pilosa Yin & Li, sp. n.,
and H. smetanai Yin & Li, sp. n. from Malaysia, and H. cibodas Yin & Li, sp. n.
from Indonesia. The two previously described species, H. hirtella Raffray, 1901
(type species) from Sri Lanka and H. falcis Yin & Li, 2010 from China are
redescribed, and a lectotype is designated for H. hirtella. Illustrations of
habitus and important diagnostic features, an identification key, and
distributional maps for all species are provided. Eleven unidentified species
represented only by females are left unnamed. Illustrations of the habitus and
the genital complex, and label data of these species are given to facilitate
future study. All available data indicates that species of Horniella typically
inhabit leaf litter of various kinds of forests, and can be most efficiently
collected by sifting and use of Winkler-Moczarski extractors.
PMID- 25112428
TI - A review of Northern Peruvian glassfrogs (Centrolenidae), with the description of
four new remarkable species.
AB - Peru is well known for amphibian diversity and endemism, yet there have been
relatively few field studies of glassfrog (Centrolenidae) diversity in this
country. Research in Colombia and Ecuador indicates that centrolenid diversity is
higher in the northern Andes. However, part of this trend appears to be due to
sampling effort. We conducted fieldwork throughout northern Peru, and based on
phylogenetic analysis of DNA sequences, combined with bioacoustic and
morphological analyses of new and available material we now recognize 33 species
from the country (versus 30 species prior to this work). Field surveys led to the
discovery of four remarkable species: Centrolene charapita new species is a
large, ornamented glassfrog that appears to be sister to Ce. geckoideum;
Chimerella corleone new species represents the second-known member of the genus
Chimerella; Cochranella guayasamini new species is the second-known member of the
genus with humeral spines; and Hyalinobatrachium anachoretus new species occurs
in the cloud forest of the east-Andean versant in Peru. In addition to the new
species described here, we provide new country records, new localities including
range extensions of up to 875 km, information on diagnostic characters and
phylogenetic relationships, call and larval descriptions, and observations on
natural history for several Peruvian centrolenids. Our results also revealed
several taxonomic problems concerning species of the genus Rulyrana, and we
conclude that R. croceopodes and R. tangarana are junior synonyms of R.
saxiscandens. By implication of our phylogenetic analyses, we recognize the
following new combinations: Espadarana audax new combination, Espadarana
durrelorum new combination, and Espadarana fernandoi new combination.
PMID- 25112429
TI - Extending statistical boosting. An overview of recent methodological
developments.
AB - BACKGROUND: Boosting algorithms to simultaneously estimate and select predictor
effects in statistical models have gained substantial interest during the last
decade. OBJECTIVES: This review highlights recent methodological developments
regarding boosting algorithms for statistical modelling especially focusing on
topics relevant for biomedical research. METHODS: We suggest a unified framework
for gradient boosting and likelihood-based boosting (statistical boosting) which
have been addressed separately in the literature up to now. RESULTS: The
methodological developments on statistical boosting during the last ten years can
be grouped into three different lines of research: i) efforts to ensure variable
selection leading to sparser models, ii) developments regarding different types
of predictor effects and how to choose them, iii) approaches to extend the
statistical boosting framework to new regression settings. CONCLUSIONS:
Statistical boosting algorithms have been adapted to carry out unbiased variable
selection and automated model choice during the fitting process and can nowadays
be applied in almost any regression setting in combination with a large amount of
different types of predictor effects.
PMID- 25112430
TI - A formative evaluation of the implementation of an upper limb stroke
rehabilitation intervention in clinical practice: a qualitative interview study.
AB - BACKGROUND: The Graded Repetitive Arm Supplementary Program (GRASP) is a hand and
arm exercise programme designed to increase the intensity of exercise achieved in
inpatient stroke rehabilitation. GRASP was shown to be effective in a randomised
controlled trial in 2009 and has since experienced unusually rapid uptake into
clinical practice. The aim of this study was to conduct a formative evaluation of
the implementation of GRASP to inform the development and implementation of a
similar intervention in the United Kingdom. METHODS: Semi-structured interviews
were conducted with therapists who were involved in implementing GRASP at their
work site, or who had experience of using GRASP. Normalisation Process Theory
(NPT), a sociological theory used to explore the processes of embedding
innovations in practice, was used to develop an interview guide. Intervention
components outlined within the GRASP Guideline Manual were used to develop
prompts to explore how therapists use GRASP in practice. Interview transcripts
were analysed using a coding frame based on implementation theory. RESULTS:
Twenty interviews were conducted across eight sites in British Columbia Canada.
Therapists identified informal networks and the free online availability of GRASP
as key factors in finding out about the intervention. All therapists reported
positive opinions about the value of GRASP. At all sites, therapists identified
individuals who advocated for the use of GRASP, and in six of the eight sites
this was the practice leader or senior therapist. Rehabilitation assistants were
identified as instrumental in delivering GRASP in almost all sites as they were
responsible for organising the GRASP equipment and assisting patients using
GRASP. Almost all intervention components were found to be adapted to some degree
when used in clinical practice; coverage was wider, the content adapted, and the
dose, when monitored, was less. CONCLUSIONS: Although GRASP has translated into
clinical practice, it is not always used in the way in which it was shown to be
effective. This formative evaluation has informed the development of a novel
intervention which aims to bridge this evidence-practice gap in upper limb
rehabilitation after stroke.
PMID- 25112431
TI - Reducing the risk of bias in health behaviour change trials: improving trial
design, reporting or bias assessment criteria? A review and case study.
AB - OBJECTIVE: It has been suggested that randomised controlled trials (RCTs) of
health behaviour change (HBC) interventions are less rigorously designed than -
for example- drug trials. This study presents an approach to clarifying whether
this is due to poor trial design, incomplete trial reporting and/or the
inappropriateness of commonly applied risk of bias assessment criteria. DESIGN:
First, a framework of key sources of bias and common strategies for reducing bias
risk is developed based on a literature review. Second, we describe the design of
a multi-site RCT evaluating the cost-effectiveness of an HIV-treatment adherence
intervention (case study). The choices made by the multidisciplinary team trying
to minimise the risk of bias are compared against the risk of bias framework.
MAIN OUTCOME MEASURES: Implementation of common strategies for reducing the risk
of bias in the case study; alternative or additional strategies applied; a
justification for each deviation from the risk of bias framework. RESULTS: Most
of the common strategies for reducing the risk of bias could be implemented.
Alternative strategies were developed for minimising the risk of performance bias
and contamination. Several additional, domain-specific risk of bias strategies
were implemented. CONCLUSIONS: The literature provides useful guidance for
reducing the risk of bias in HBC trials. Yet, the case study suggests that HBC
trial designers may face specific challenges that require alternative/additional
measures for reducing the risk of bias. Using the risk of bias justification
table (RATIONALE) could lead to better-designed HBC trials, more comprehensive
trial reports and the data necessary for evaluating the appropriateness of
commonly applied risk of bias assessment criteria to HBC trials.
PMID- 25112432
TI - Experiences of and responses to disrespectful maternity care and abuse during
childbirth; a qualitative study with women and men in Morogoro Region, Tanzania.
AB - BACKGROUND: Interventions to reduce maternal mortality have focused on delivery
in facilities, yet in many low-resource settings rates of facility-based birth
have remained persistently low. In Tanzania, rates of facility delivery have
remained static for more than 20 years. With an aim to advance research and
inform policy changes, this paper builds on a growing body of work that explores
dimensions of and responses to disrespectful maternity care and abuse during
childbirth in facilities across Morogoro Region, Tanzania. METHODS: This research
drew on in-depth interviews with 112 respondents including women who delivered in
the preceding 14 months, their male partners, public opinion leaders and
community health workers to understand experiences with and responses to abuse
during childbirth. All interviews were recorded, transcribed, translated and
coded using Atlas.ti. Analysis drew on the principles of Grounded Theory.
RESULTS: When initially describing birth experiences, women portrayed encounters
with providers in a neutral or satisfactory light. Upon probing, women recounted
events or circumstances that are described as abusive in maternal health
literature: feeling ignored or neglected; monetary demands or discriminatory
treatment; verbal abuse; and in rare instances physical abuse. Findings were
consistent across respondent groups and districts. As a response to abuse, women
described acquiescence or non-confrontational strategies: resigning oneself to
abuse, returning home, or bypassing certain facilities or providers. Male
respondents described more assertive approaches: requesting better care, paying a
bribe, lodging a complaint and in one case assaulting a provider. CONCLUSIONS:
Many Tanzanian women included in this study experienced unfavorable conditions
when delivering in facilities. Providers, women and their families must be made
aware of women's rights to respectful care. Recommendations for further research
include investigations of the prevalence and dimensions of disrespectful care and
abuse, on mechanisms for women and their families to effectively report and
redress such events and on interventions that could mitigate neglect or isolation
among delivering women. Respectful care is a critical component to improve
maternal health.
PMID- 25112433
TI - Impact of pre-imputation SNP-filtering on genotype imputation results.
AB - BACKGROUND: Imputation of partially missing or unobserved genotypes is an
indispensable tool for SNP data analyses. However, research and understanding of
the impact of initial SNP-data quality control on imputation results is still
limited. In this paper, we aim to evaluate the effect of different strategies of
pre-imputation quality filtering on the performance of the widely used imputation
algorithms MaCH and IMPUTE. RESULTS: We considered three scenarios: imputation of
partially missing genotypes with usage of an external reference panel, without
usage of an external reference panel, as well as imputation of completely un
typed SNPs using an external reference panel. We first created various datasets
applying different SNP quality filters and masking certain percentages of
randomly selected high-quality SNPs. We imputed these SNPs and compared the
results between the different filtering scenarios by using established and newly
proposed measures of imputation quality. While the established measures assess
certainty of imputation results, our newly proposed measures focus on the
agreement with true genotypes. These measures showed that pre-imputation SNP
filtering might be detrimental regarding imputation quality. Moreover, the
strongest drivers of imputation quality were in general the burden of missingness
and the number of SNPs used for imputation. We also found that using a reference
panel always improves imputation quality of partially missing genotypes. MaCH
performed slightly better than IMPUTE2 in most of our scenarios. Again, these
results were more pronounced when using our newly defined measures of imputation
quality. CONCLUSION: Even a moderate filtering has a detrimental effect on the
imputation quality. Therefore little or no SNP filtering prior to imputation
appears to be the best strategy for imputing small to moderately sized datasets.
Our results also showed that for these datasets, MaCH performs slightly better
than IMPUTE2 in most scenarios at the cost of increased computing time.
PMID- 25112434
TI - Prostate cancer in a man with a BRCA2 mutation and a personal history of
bilateral breast cancer.
AB - Men with a BRCA2 mutation face substantial lifetime risks for the development of
both breast and prostate cancer. A male who was initially diagnosed with breast
cancer at the age of 32 was subsequently diagnosed at age 77 with both
contralateral breast cancer and prostate cancer. He was found to be BRCA2
mutation carrier. The patient was treated with contralateral mastectomy, breast
irradiation, prostate irradiation and adjuvant endocrine therapy. At age 83 he
died of metastatic prostate cancer. Our case underscores the observation that
BRCA2 mutation carriers are at risk for multiple cancers, including contralateral
breast cancer, and illustrates the need for current practice recommendations for
the early detection of breast and prostate cancer in men with BRCA2 mutations.
PMID- 25112435
TI - Accumulation of cadmium in and its effect on the midgut gland of terrestrial
snail Helix pomatia L. from urban areas in Poland.
AB - The objectives of this study were (1) to determine cadmium (Cd) accumulation in
the midgut gland of a land snail Helix pomatia L. inhabiting residential areas of
the 14 largest cities in Poland, and (2) to examine whether the accumulated Cd
exerted any toxic effects. The average accumulation of Cd in the midgut gland of
snails, weighing 16-18 g, ranged from 7.00 to 87.3 ug/g dry weight (0.06-0.77
umol/g) and differed significantly among animals from the various urban areas.
This difference in Cd accumulation was not related to city population, but was
associated with the topsoil Cd (R(2) = 0.868, p < 0.0001). The tissue Cd was not
found to produce toxicity (histopathology, programmed cell death, lipofuscin
formation or lipid peroxidation), probably due to the induction of sufficiently
high quantities of metallothionein and glutathione, well-known protective
molecules.
PMID- 25112436
TI - YLT192, a novel, orally active bioavailable inhibitor of VEGFR2 signaling with
potent antiangiogenic activity and antitumor efficacy in preclinical models.
AB - Antagonizing vascular endothelial growth factor receptor 2 (VEGFR2) to block
angiogenesis has been applied toward cancer therapy for its role in promoting
cancer growth and metastasis. However, most these clinical anticancer drugs have
unexpected side effects. Development of novel VEGFR2 inhibitors with less
toxicity remains an urgent need. In this study, we describe a novel, well
tolerated, and orally active VEGFR2 inhibitor, YLT192, which inhibits tumor
angiogenesis and growth. YLT192 significantly inhibited kinase activity of VEGFR2
and suppressed proliferation, migration, invasion, and tube formation of human
umbilical vascular endothelial cells (HUVEC) in vitro. In addition, it inhibited
VEGF-induced phosphorylation of VEGFR2 and its downstream signaling regulator in
HUVEC. Zebrafish embryonic models and alginate-encapsulated tumor cell assays
indicated YLT192 also inhibited angiogenesis in vivo. Moreover, YLT192 could
directly inhibit proliferation and induce apoptosis of cancer cells in vitro and
in vivo. Oral administration of YLT192 at a dose of 100 mg/kg/day could markedly
inhibited human tumor xenograft growth without causing obvious toxicities. It
decreased microvessel densities (MVD) in tumor sections. It also shows good
safety profiles in the studies with mice and rats. Taken together, these
preclinical evaluations suggest that YLT192 inhibits angiogenesis and may be a
promising anticancer drug candidate.
PMID- 25112440
TI - Cystic kidney disease: Intracellular clusterin implicated in nephropathic
cystinosis.
PMID- 25112438
TI - Child Eating Behaviors and Caregiver Feeding Practices in Children with Autism
Spectrum Disorders.
AB - OBJECTIVE: This pilot study compared children with autism spectrum disorders
(ASD) and typically developing children (TDC) on weight-related outcomes and
caregiver-reported child eating behaviors and feeding practices. DESIGN AND
SAMPLE: Cross-sectional study. Caregivers of 25 children with ASD and 30 TDC,
ages 4-6. METHODS: Caregivers completed validated questionnaires that assessed
child eating behaviors and feeding practices. Children's height, weight, and
waist circumference were measured. RESULTS: Children with ASD, when compared to
TDC, showed significantly greater abdominal waist circumferences (p = .01) and
waist-to-height ratios (p < .001). Children with ASD with atypical oral sensory
sensitivity exhibited greater food avoidance behaviors, including reluctance to
eat novel foods (p = .004), being selective about the range of foods they accept
(p = .03), and undereating due to negative emotions (p = .02), than children with
ASD with typical oral sensory sensitivity. Caregivers of children with ASD with
atypical oral sensory sensitivity reported using food to regulate negative child
emotions to a greater extent than caregivers of children with typical oral
sensory sensitivity (p = .02). DISCUSSION: Children with ASD, especially those
with atypical oral sensory sensitivity, are at increased risk for food avoidance
behaviors and may require additional support in several feeding domains.
PMID- 25112437
TI - Proanthocyanidins from grape seeds inhibit UV-radiation-induced immune
suppression in mice: detection and analysis of molecular and cellular targets.
AB - Ultraviolet (UV)-radiation-induced immunosuppression has been linked with the
risk of skin carcinogenesis. Approximately, 2 million new cases of skin cancers,
including melanoma and nonmelanoma, diagnosed each year in the USA and therefore
have a tremendous bad impact on public health. Dietary phytochemicals are
promising options for the development of effective strategy for the prevention of
photodamaging effects of UV radiation including the risk of skin cancer. Grape
seed proanthocyanidins (GSPs) are such phytochemicals. Dietary administration of
GSPs with AIN76A control diet significantly inhibits UV-induced skin tumor
development as well as suppression of immune system. UV-induced suppression of
immune system is commonly determined using contact hypersensitivity (CHS) model
which is a prototype of T-cell-mediated immune response. We present evidence that
inhibition of UV-induced suppression of immune system by GSPs is mediated
through: (i) the alterations in immunoregulatory cytokines, interleukin (IL)-10
and IL-12, (ii) DNA repair, (iii) stimulation of effector T cells and (iv) DNA
repair-dependent functional activation of dendritic cells in mouse model. These
information have important implications for the use of GSPs as a dietary
supplement in chemoprevention of UV-induced immunosuppression as well as
photocarcinogenesis.
PMID- 25112443
TI - Would medical students enter an exclusion zone in an infected district with a
high mortality rate? An analysis of book reports on 28 (secondary publication).
AB - This study aimed to ascertain whether medical students would enter a closed area
where there was a raging epidemic of an infectious disease with a high fatality
rate, and includes reasons for the students entering or refusing to enter.
Participants included 50 second-year medical students. They were assigned to read
a novel entitled 28, written by Youjeong Jeong, and discuss it in groups. Using
their book reports, their decisions of whether or not to enter Hwayang, the city
from the novel, and the reasons for their decisions were analyzed; we furthermore
investigated the factors affecting their decisions. Among the 50 respondents, 18
students (36%) answered that they would enter, and the remaining 32 students
(64%) answered that they would not enter the zone. The reasons given for entering
were responsibility (44%), sense of ethics (33%), social duty (17%), and sense of
guilt (6%). The reasons the students provided for not entering were inefficiency
(44%), worry regarding family (28%), needlessness of sacrifice (19%), and safety
not ensured (9%). Students who had four or fewer family members were more likely
to enter Hwayang than were students who had five or more family members (odds
ratio, 1.85). Students who had completed over 100 hours of volunteer work were
more likely to enter Hwayang than were students who had volunteered less than 100
hours (odds ratio, 2.04). Owing to their "responsibility" as a doctor, 36% of
medical students answered that they would enter an exclusion zone in an infected
district with a high fatality rate. However, 64% answered they would not enter
because of "inefficiency." For the medical students it is still a question 'To
enter or not to enter?'
PMID- 25112441
TI - Transplantation: Alemtuzumab induction reduces acute rejection risk.
PMID- 25112444
TI - Is a medical humanities test needed in the National Medical Licensing Examination
of Korea? Opinions of medical students and physician writers (secondary
publication).
AB - The purpose of this study was to examine the opinions of medical students and
physician writers regarding the medical humanities as a subject and its inclusion
in the medical school curriculum. Furthermore, we addressed whether an assessment
test should be added to the National Medical Licensing Examination of Korea
(KMLE). A total of 192 medical students at Inha University and 39 physician
writers registered with the Korean Association of Physician Essayists and the
Korean Association of Physician Poets participated in this study. They were asked
to answer a series of questionnaires. Most medical students (59%) and all
physician writers (100%) answered that the medical humanities should be included
in the medical school curriculum to train good physicians. They thought that the
KMLE did not currently include an assessment of the medical humanities (medical
students 69%, physician writers 69%). Most physician writers (87%; Likert scale,
4.38+/-0.78) felt that an assessment of the medical humanities should be included
in the KMLE. Half of the medical students (51%; Likert scale, 2.51+/-1.17) were
against including it in the KMLE, which they would have to pass after several
years of study. For the preferred field of assessment, medical ethics was the
most commonly endorsed subject (medical students 59%, physician writers 39%). The
most frequently preferred evaluation method was via an interview (medical
students 45%, physician writers 33%). In terms of the assessment of the medical
humanities and the addition of this subject to the KMLE, an interview-based
evaluation should be developed.
PMID- 25112446
TI - Documentary research and evaluation in medical education.
PMID- 25112447
TI - Assessing the reliability and validity of the Revised Two Factor Study Process
Questionnaire (R-SPQ2F) in Ghanaian medical students.
AB - PURPOSE: We investigated the validity and reliability of the Revised Two Factor
Study Process Questionnaire (R-SPQ2F) in preclinical students in Ghana. METHODS:
The R-SPQ2F was administered to 189 preclinical students of the University for
Development Studies, School of Medicine and Health Sciences. Both descriptive and
inferential statistics with Cronbach's alpha test and factor analysis were done.
RESULTS: The mean age of the students was 22.69+/- 0.18years, 60.8% (n=115) were
males and 42.3% (n=80) were in their second year of medical training. The
students had higher mean deep approach scores (31.23+/-7.19) than that of surface
approach scores (22.62+/-6.48). Findings of the R-SPQ2F gave credence to a
solution of two-factors indicating deep and surface approaches accounting for
49.80% and 33.57%, respectively, of the variance. The scales of deep approach
(Cronbach's alpha, 0.80) and surface approach (Cronbach's alpha, 0.76) and their
subscales demonstrated an internal consistency that was good. The factorial
validity was comparable to other studies. CONCLUSION: Our study confirms the
construct validity and internal consistency of the R-SPQ2F for measuring
approaches to learning in Ghanaian preclinical students. Deep approach was the
most dominant learning approach among the students. The questionnaire can be used
to measure students' approaches to learning in Ghana and in other African
countries.
PMID- 25112445
TI - Confounding factors in using upward feedback to assess the quality of medical
training: a systematic review.
AB - PURPOSE: Upward feedback is becoming more widely used in medical training as a
means of quality control. Multiple biases exist, thus the accuracy of upward
feedback is debatable. This study aims to identify factors that could influence
upward feedback, especially in medical training. METHODS: A systematic review
using a structured search strategy was performed. Thirty-five databases were
searched. Results were reviewed and relevant abstracts were shortlisted. All
studies in English, both medical and non-medical literature, were included. A
simple pro-forma was used initially to identify the pertinent areas of upward
feedback, so that a focused pro-forma could be designed for data extraction.
RESULTS: A total of 204 articles were reviewed. Most studies on upward feedback
bias were evaluative studies and only covered Kirkpatrick level 1-reaction. Most
studies evaluated trainers or training, were used for formative purposes and
presented quantitative data. Accountability and confidentiality were the most
common overt biases, whereas method of feedback was the most commonly implied
bias within articles. CONCLUSION: Although different types of bias do exist,
upward feedback does have a role in evaluating medical training. Accountability
and confidentiality were the most common biases. Further research is required to
evaluate which types of bias are associated with specific survey characteristics
and which are potentially modifiable.
PMID- 25112448
TI - Reflective writing and its impact on empathy in medical education: systematic
review.
AB - PURPOSE: Medical schools are increasingly aware of the ways in which physician
empathy can have a profound impact on patients' lives and have developed
humanities initiatives to address this concern. Reflective writing in particular
is more commonly promoted in medical curricula, but there is limited research on
the impact of reflective writing on medical student empathy levels. It aims to
find the emotional effects of reflective writing interventions on medical and
healthcare students by systemic review. METHODS: Two investigators independently
reviewed educational publications for critical analysis. This review focused
systematically on quantitative papers that measure the impact of reflective
writing on empathy. RESULTS: Of the 1,032 studies found on Medline and CINAHL,
only 8 used quantitative measures pre- and postwritten reflection to measure any
impact on empathy outcomes. The outcomes measured included impact of reflective
writing exercises on student wellness, aptitude, and/or clinical skills. Of these
studies, a significant change in student empathy was observed in 100% of the
studies, demonstrating a significant change in outcomes. CONCLUSION: Although the
lack of homogeneity in outcome measurement in the literature limits possible
conclusion from this review, the overwhelmingly positive reporting of outcomes
suggests that reflective writing should be considered in any medical curriculum.
PMID- 25112449
TI - Strengthening student communication through pediatric simulated patient
encounters.
AB - As medical students enter the role of physician, clinical outcomes not only rely
on their mastery of clinical knowledge, but also on the effectiveness in which
they can communicate with patients and family members. While students typically
have numerous opportunities to practice clinical communication with adult
patients, such practice in pediatric settings is limited. This study examines if
simulated patient (SP) encounters strengthen third-year medical students'
communication skills during the pediatrics clerkship. During 2011-2013, three SP
encounters (comprising 3 pediatric scenarios) were incorporated into a pediatrics
clerkship at one United States medical school to give students a safe venue to
practice advanced communication with observation and direct feedback. Third-year
medical students engaged in the scenarios and received both written and oral
feedback from an evaluator observing the encounter. With IRB approval, students'
self-perceived confidence and abilities at performing the advanced communication
skills were measured using an eightitem, Likert scale questionnaire administered
pre and post the SP encounter. Pre- and post-questionnaires (n=215; response
rate, 96%) analyzed using a Wilcoxon-matched pairs signed-rank test demonstrated
statistically significant increases in students' perception of their confidence
and abilities regarding their performance (P<0.05; Bonferroni correction,
P<0.006). There was an increases in student confidence and self-perceived ability
in: first, communicating with children and family members of young patients;
second, managing confrontational situations involving parents; third, performing
a thorough psychosocial history with an adolescent; and fourth, using Evidence
Based Medicine to motivate parents.
PMID- 25112450
TI - Ranolazine treatment for myocardial infarction? Effects on the development of
necrosis, left ventricular function and arrhythmias in experimental models.
AB - Ranolazine, an inhibitor of the late current of the cardiac action potential
(late I(Na)), is a well established clinical treatment for chronic angina. The
late INa in cardiac myocytes also plays an important role in the pathophysiology
of acute myocardial ischemia and reperfusion, and thus is a potential therapeutic
target to ameliorate consequences of myocardial infarction. In experimental
animal models, ranolazine has been shown to reduce myocardial infarct size,
improve left ventricular function, decrease ischemia/reperfusion-induced
arrhythmias and improve outcome in heart failure. Here we focus specifically on
data from in vivo animal studies of myocardial ischemia and reperfusion.
PMID- 25112452
TI - Thermal human biometeorological conditions and subjective thermal sensation in
pedestrian streets in Chengdu, China.
AB - The outdoor thermal environment of a public space is highly relevant to the
thermal perception of individuals, thereby affecting the use of space. This study
aims to connect thermal human biometeorological conditions and subjective thermal
sensation in hot and humid regions and to find its influence on street use. We
performed a thermal comfort survey at three locations in a pedestrian precinct of
Chengdu, China. Meteorological measurements and questionnaire surveys were used
to assess the thermal sensation of respondents. The number of people visiting the
streets was counted. Meanwhile, mean radiant temperature (T mrt) and the
physiological equivalent temperature (PET) index were used to evaluate the
thermal environment. Analytical results reveal that weather and street design
drive the trend of diurnal micrometeorological conditions of the street. With the
same geometry and orientation, a street with no trees had wider ranges of
meteorological parameters and a longer period of discomfort. The neutral
temperature in Chengdu (24.4 degrees C PET) is similar to that in Taiwan,
demonstrating substantial human tolerance to hot conditions in hot and humid
regions. Visitors' thermal sensation votes showed the strongest positive
relationships with air temperature. Overall comfort level was strongly related to
every corresponding meteorological parameter, indicating the complexity of
people's comfort in outdoor environments. In major alleys with multiple
functions, the number of people in the street decreased as thermal indices
increased; T mrt and PET had significant negative correlations with the number of
people. This study aids in understanding pedestrian street use in hot and humid
regions.
PMID- 25112453
TI - Efficacy of daptomycin lock therapy in the treatment of bloodstream infections
related to long-term catheter.
AB - BACKGROUND: Concomitant systemic and intracatheter antibiotic therapy is a
therapeutic option for catheter-related bloodstream infections (CRBSI) in patient
fitted with long-term intravenous central catheters. CRBSI are mainly caused by
Gram-positive bacteria. Daptomycin (DPT) is an antibiotic active against Gram
positive bacteria with high bactericidal activity and good biofilm penetration.
OBJECTIVE: To study the efficacy of DPT given systemically and as lock therapy in
the treatment of CRBSI. MATERIALS AND METHODS: A retrospective review was
conducted of adult patients with a long-term central venous catheter (CVC)
receiving both systemic intravenous and intracatheter lock therapy for CRBSI. The
primary outcome was catheter maintenance, following clinical success and
microbiological eradication. RESULTS: Eight patients who had failed previous
standard therapy (vancomycin 7, cefazolin 1) were included in the study. In all
but one, coagulase-negative staphylococci were repeatedly isolated. The other
patient had enterococcal infection. DPT, given intravenously and as lock therapy,
was successful in six of eight cases. The mean time to negative blood cultures
was 2 days (range 1-6). In two cases neither clinical nor microbiological
response was documented and the catheter was removed. DISCUSSION: Systemic and
intracatheter therapy with DPT is feasible, carries no toxicity and is apparently
effective. DPT might be a suitable therapeutic option in CRBSI to achieve CVC
sterilization and preserve the catheter.
PMID- 25112454
TI - Navigated three-dimensional T1-weighted gradient-echo sequence for gadoxetic acid
liver magnetic resonance imaging in patients with limited breath-holding
capacity.
AB - PURPOSE: To determine whether a navigator-gated three-dimensional T1-weighted
gradient-echo sequence (T1W-GRE, navigated LAVA) can improve diagnostic
performance for the detection of focal liver lesions (FLLs) compared to standard
breath-hold (BH) T1W-GRE breath-hold LAVA (BH-LAVA) during the hepatobiliary
phase (HBP) of gadoxetic acid liver magnetic resonance imaging (MRI) in patients
with limited breath-holding capacity. MATERIALS AND METHODS: This retrospective
study was approved by our institutional review board and the requirement for
informed consent was waived. We included 372 patients who underwent liver MRI
including both navigated LAVA and BH-LAVA sequences. Overall image quality of the
two HBP image sets was compared. In patients with limited breath-holding
capacity, diagnostic performances in detecting FLLs on the two HBP images were
compared using jackknife-alternative free-response receiver-operating
characteristic (JAFROC) analysis by two reviewers. RESULTS: There were 13 cases
(13/372; 3.5%) of image acquisition failure using the navigated LAVA sequence due
to severe irregular breathing, and 50 of 359 patients had limited breath-holding
capacity. In these patients, overall image quality of navigated LAVA (2.78 +/-
0.95) was significantly better than that of BH-LAVA (2.42 +/- 0.81, P < 0.005),
and both readers showed significantly higher JAFROC figure-of-merit values with
navigated LAVA compared to BH-LAVA (0.94 and 0.86 in reviewer 1, respectively;
0.89 and 0.83 in reviewer 2, respectively, P < 0.005). Overall image quality of
navigated LAVA was also better than that of BH-LAVA in patients with sufficient
breath-holding capacity (n = 309, 3.96 +/- 0.88, 3.81 +/- 0.66, respectively, P <
0.001). CONCLUSION: The navigated LAVA sequence could provide better image
quality and diagnostic performance in detecting FLLs than BH-LAVA in patients
with limited breath-holding capacity during HBP of gadoxetic acid MRI.
PMID- 25112457
TI - Drug-target interaction prediction via chemogenomic space: learning-based
methods.
AB - INTRODUCTION: Identification of the interaction between drugs and target proteins
is a crucial task in genomic drug discovery. The in silico prediction is an
appropriate alternative for the laborious and costly experimental process of drug
target interaction prediction. Developing a variety of computational methods
opens a new direction in analyzing and detecting new drug-target pairs. AREAS
COVERED: In this review, we will focus on chemogenomic methods which have
established a learning framework for predicting drug-target interactions.
Learning-based methods are classified into supervised and semi-supervised, and
the supervised learning methods are studied as two separate parts including
similarity-based methods and feature-based methods. EXPERT OPINION: In spite of
many improvements for pharmacology applications by learning-based methods, there
are many over simplification settings in construction of predictive models that
may lead to over-optimistic results on drug-target interaction prediction.
PMID- 25112455
TI - Efficient production of single-chain fragment variable-based N-terminal
trimerbodies in Pichia pastoris.
AB - BACKGROUND: Recombinant antibodies are highly successful in many different
pathological conditions and currently enjoy overwhelming recognition of their
potential. There are a wide variety of protein expression systems available, but
almost all therapeutic antibodies are produced in mammalian cell lines, which
mimic human glycosylation. The production of clinical-grade antibodies in
mammalian cells is, however, extremely expensive. Compared to mammalian systems,
protein production in yeast strains such as Pichia pastoris, is simpler, faster
and usually results in higher yields. RESULTS: In this work, a trivalent single
chain fragment variable (scFv)-based N-terminal trimerbody, specific for the
human carcinoembryonic antigen (CEA), was expressed in human embryonic kidney 293
cells and in Pichia pastoris. Mammalian- and yeast-produced anti-CEA trimerbody
molecules display similar functional and structural properties, yet, the yield of
trimerbody expressed in P. pastoris is about 20-fold higher than in human cells.
CONCLUSIONS: P. pastoris is an efficient expression system for multivalent
trimerbody molecules, suitable for their commercial production.
PMID- 25112458
TI - The frequency of re-planning and its variability dependent on the modification of
the re-planning criteria and IGRT correction strategy in head and neck IMRT.
AB - BACKGROUND: To analyse the frequency of re-planning and its variability dependent
on the IGRT correction strategy and on the modification of the dosimetric
criteria for re-planning for the spinal cord in head and neck IG-IMRT. METHODS:
Daily kV-control-CTs of six head and neck patients (=175 CTs) were analysed. All
volumes of interest were re-contoured using deformable image registration. Three
IGRT correction strategies were simulated and the resulting dose distributions
were computed for all fractions. Different sets of criteria with varying dose
thresholds for re-planning were investigated. All sets of criteria ensure
equivalent target coverage of both CTVs, but vary in the tolerance threshold of
the spinal cord. RESULTS: The variations of the D95 and D2 in respect to the
planned values ranged from -7% to +3% for both CTVs, and -2% to +6% for the
spinal cord. Despite different correction vectors of the three IGRT strategies,
the dosimetric differences were small. The number of fractions not requiring re
planning varied between 0% and 11% dependent on the applied IGRT correction
strategy. In contrast, this number ranged between 32% and 70% dependent on the
dosimetric thresholds, even though these thresholds were only gently modified.
CONCLUSIONS: The more precise the planned dose needs to be maintained over the
treatment course, the more frequently re-planning is required. The influence of
different IGRT correction strategies, even though geometrically notable, was
found to be of only limited relevance for the re-planning frequency. In contrast,
the definition and modification of thresholds for re-planning have a major impact
on the re-planning frequency.
PMID- 25112459
TI - Month-wise estimates of tobacco smoking during pregnancy for the United States,
2002-2009.
AB - The timing of prenatal exposure to tobacco cigarette smoking can be crucial for
the developing fetus. Pushing the field beyond prior pregnancy trimester-focused
smoking estimates, we estimated month-specific prevalence proportions for tobacco
cigarette smoking among pregnant and non-pregnant women of the United States,
with consideration of tobacco dependence (TD) as well. In advance, we posited
that pregnancy onset might prompt smoking cessation in early months, before the
end of the 1st trimester, and that TD might account for sustained smoking in
later months, especially months 8-9, when there are added reasons to quit.
Estimates are from the 2002-2009 National Surveys on Drug Use and Health
Restricted-Data Analysis System (R-DAS), with large nationally representative
samples of US civilians, including 12-44 year old women (n ~ 70,000) stratified
by pregnancy status and month of pregnancy, with multi-item assessment of TD as
well as recently active smoking. Age was held constant via the Breslow-Day
indirect standardization approach, a methodological detail of potential interest
to other research teams conducting online R-DAS analyses. Among 12-44 year old
women in Month 1 of pregnancy, as well as non-pregnant women, just over one in
four was a recently active smoker (26-27 %), and approximately one-half of these
smokers qualified as a TD case (52 %). Corresponding estimates for women in Month
3 were 17.6 % and two-thirds, respectively, lending some support for our advance
hypotheses. Nonetheless, our a priori TD hypothesis about Months 8-9 seems to be
contradicted: an increased concentration of TD among smokers surfaced early in
pregnancy. Evidence of a possible ameliorative pregnancy effect on smoking
prevalence as well as TD's effect on smoking persistence might be seen quite
early in pregnancy. Substitution of a month-specific view for the traditional
trimester view sheds new light on how pregnancy might shape smoking behavior
before the end of trimester 1, with TD seeming to thwart a public health goal of
100 % cessation, early in pregnancy.
PMID- 25112451
TI - Evaluation of the impact of implementing the emergency medical services traumatic
brain injury guidelines in Arizona: the Excellence in Prehospital Injury Care
(EPIC) study methodology.
AB - Traumatic brain injury (TBI) exacts a great toll on society. Fortunately, there
is growing evidence that the management of TBI in the early minutes after injury
may significantly reduce morbidity and mortality. In response, evidence-based
prehospital and in-hospital TBI treatment guidelines have been established by
authoritative bodies. However, no large studies have yet evaluated the
effectiveness of implementing these guidelines in the prehospital setting. This
article describes the background, design, implementation, emergency medical
services (EMS) treatment protocols, and statistical analysis of a prospective,
controlled (before/after), statewide study designed to evaluate the effect of
implementing the EMS TBI guidelines-the Excellence in Prehospital Injury Care
(EPIC) study (NIH/NINDS R01NS071049, "EPIC"; and 3R01NS071049-S1, "EPIC4Kids").
The specific aim of the study is to test the hypothesis that statewide
implementation of the international adult and pediatric EMS TBI guidelines will
significantly reduce mortality and improve nonmortality outcomes in patients with
moderate or severe TBI. Furthermore, it will specifically evaluate the effect of
guideline implementation on outcomes in the subgroup of patients who are
intubated in the field. Over the course of the entire study (~9 years), it is
estimated that approximately 25,000 patients will be enrolled.
PMID- 25112460
TI - Therapeutic options after treatment failure in rheumatoid arthritis or
spondyloarthritides.
AB - The prognosis for patients with rheumatoid arthritis or spondyloarthritides has
improved dramatically due to earlier diagnosis, recognition of the need to treat
early with conventional synthetic disease-modifying antirheumatic drugs
(csDMARDs), alone or in combinations, the establishment of treatment targets, and
the development of biological DMARDs (bDMARDs). Many patients are now able to
achieve clinical remission or low disease activity with therapy, and reduce or
eliminate systemic corticosteroid use. Guidelines recommend methotrexate as a
first-line agent for the initial treatment of rheumatoid arthritis; however, a
majority of patients will require a change of csDMARD or step up to combination
therapy with the addition of another csDMARD or a bDMARD. However, treatment
failure is common and switching to a different therapy may be required. The large
number of available treatment options, combined with a lack of comparative data,
makes the choice of a new therapy complex and often not evidence based. We
summarize and discuss evidence to inform treatment decisions in patients who
require a change in therapy, including baseline factors that may predict response
to therapy.
PMID- 25112461
TI - Comparing patient outcomes of academician-preceptors, hospitalist-preceptors, and
hospitalists on internal medicine services in an academic medical center.
AB - BACKGROUND: Patient outcomes with hospitalist care have been studied in many
settings, yet little is known about how hospitalist care interacts with trainee
care to affect patient outcomes in teaching hospitals. OBJECTIVES: The aim of
this study was to compare patient outcomes between hospitalist-preceptors and
hospitalists working alone (isolating the effect of housestaff involvement), and
between hospitalist-preceptors and academician-preceptors (isolating the effect
of attending type, given housestaff involvement). DESIGN: A four-year
retrospective cohort study of patients (n = 13,313) admitted to all internal
medicine services at an academic medical center from July 2008 to June 2012. MAIN
MEASURES: Using generalized estimating equations, we measured readmission within
30 days, hospital length of stay, cost of the index hospitalization, and
cumulative cost including readmissions within 30 days. KEY RESULTS: In the
adjusted models, 30-day readmission odds were higher for academic-preceptors (OR,
1.14 [95% CI, 1.03 - 1.26]) and hospitalist-preceptors (OR, 1.10 [95% CI, 1.002 -
1.21]) than for hospitalists working alone. Compared with hospitalists working
alone, academic-preceptors were associated with shorter length of stay (mean
difference, 0.27 days [95% CI, 0.18 - 0.38]), lower index hospitalization costs
(mean difference, $386 [95% CI, $192 - $576]), but similar cumulative inpatient
costs within 30 days of discharge. Compared with hospitalists working alone,
hospitalist-preceptors were associated with shorter length of stay (mean
difference, 0.34 days [95% CI, 0.26 - 0.42]), lower index hospitalization cost
(mean difference, $570 [95% CI, $378 - $760]), and a trend toward lower
cumulative cost (mean difference, $1347 [95% CI, $254 - $2,816]). CONCLUSIONS:
Preceptor-led medicine services were associated with more readmissions within 30
days, shorter lengths of stay, and lower index admission-associated costs.
However, when considering cumulative hospitalization costs, patients discharged
by academician-preceptors incurred the highest cost and hospitalist-preceptors
incurred the lowest cost.
PMID- 25112462
TI - Gender differences in resources and negotiation among highly motivated physician
scientists.
AB - BACKGROUND: Resources, including space, equipment, funding, personnel, and
protected time, are essential in academic medical careers. Negotiation often
plays a key role in the distribution of these resources. OBJECTIVE: This study
explored gender differences in resources, negotiation behaviors, and negotiation
outcomes in a sample of career development awardees. DESIGN: Postal survey of a
cohort of 1,708 clinician-researchers with responses from 1,275 (75 % response
rate). PARTICIPANTS: Researchers who received NIH K08 or K23 awards between 2006
and 2009. MAIN MEASURES: We analyzed gender differences in resources, negotiation
behaviors, and negotiation outcomes, using regression models adjusted for race, K
award type, K award year, degree, academic rank, specialty, and institutional
funding. KEY RESULTS: Over one-fifth of respondents reported inadequate access to
research space and one-third had asked for increased space or equipment.
Perceived adequacy of these physical resources did not differ significantly by
gender, but a higher proportion of women reported inadequate access to grants
administrators (34.8 %) and statistical support (49.9 %) than men (26.9 %; p =
0.002 and 43.4 %; p = 0.025, respectively). Women were more likely to have asked
for reduction in clinical hours (24.1 % vs. 19.3 %; p = 0.02) and to have raised
concerns about unfair treatment (50.2 % vs. 38.2 %; p < 0.001). Overall, 42.9 %
of women and 35.9 % of men asked for a raise in the two years preceding the
survey (p = 0.09), and among those who had asked for increased resources, the
likelihood that the request was granted did not differ significantly by gender.
CONCLUSION: Many career development award recipients report resource needs and
negotiate for increased resources. Gender differences in perceived access to
research support personnel exist even in this select cohort of K awardees.
Institutions should provide appropriate training in negotiation and ensure
adequate and equitable distribution of resources to promote academic success.
PMID- 25112463
TI - The shift of segmental contribution ratio in patients with herniated disc during
cervical lateral bending.
AB - BACKGROUND: Abnormal intervertebral movements of spine have been reported to be
associated with trauma and pathological conditions. The importance of objective
spinal motion imaging assessment in the frontal plane was frequently
underestimated. The clinical evaluation of the segmental motion contribution
could be useful for detecting the motion pattern of individual vertebrae.
Therefore the purpose of this study was to investigate the shift of segmental
contribution ratio in patients with herniated disc during cervical lateral
bending to provide additional insights to cervical biomechanics. METHODS: A total
of 92 subjects (46 healthy adult subjects and 46 disc-herniated patients) were
enrolled in this case-control study. The motion images during cervical lateral
bending movements were digitized using a precise image protocol to analyze the
intervertebral motion and contribution. RESULTS: Our results showed that the
intervertebral angulation during cervical lateral bending for the C2/3 to C6/7
segments were 7.66 degrees +/-2.37 degrees , 8.37 degrees +/-2.11 degrees , 8.91
degrees +/-3.22 degrees , 7.19 degrees +/-2.29 degrees , 6.31 degrees +/-2.11
degrees , respectively for the healthy subjects. For the patients with herniated
disc, the intervertebral angulation for the C2/3 to C6/7 segments were 6.87
degrees +/-1.67 degrees , 7.83 degrees +/-1.79 degrees , 7.73 degrees +/-2.71
degrees , 5.13 degrees +/-2.05 degrees , 4.80 degrees +/-1.93 degrees ,
respectively. There were significant angulation and translational differences
between healthy subjects and the patients with herniated disc in the C5/6 and
C6/7 segments (P=0.001-0.029). The segmental contributions of the individual
vertebral segments were further analyzed. There was a significant increase in
segmental contribution ratio of C3/4 (P=0.048), while a significant decrease in
contribution ratio of C5/6 (P=0.037) was observed in the patients with herniated
disc. Our results indicated that the segmental contribution shifted toward the
middle cervical spine in the patients with herniated disc. CONCLUSIONS: The
segmental contributions of cervical spine during lateral bending movement were
first described based on the validated radiographic protocol. The detection of
the shift of segmental contribution ratio could be helpful for the diagnosis the
motion abnormality resulted from the disc or, facet pathologies, and arthritic
changes of cervical spine.
PMID- 25112464
TI - Synthesis and antiviral bioactivity of novel 3-((2-((1E,4E)-3-oxo-5-arylpenta-1,4
dien-1-yl)phenoxy)methyl)-4(3H)-quinazolinone derivatives.
AB - A series of novel 3-((2-((1E,4E)-3-oxo-5-arylpenta-1,4-dien-1-yl)phenoxy)methyl)
4(3H)-quinazolinone derivatives were designed and synthesized. Antiviral
bioassays indicated that a few of the compounds exhibited higher antiviral
activities against tobacco mosaic virus (TMV) in vivo than the commercial agent
ningnanmycin. In particular, compounds A5, A12, A25, and A27 possessed
appreciable curative bioactivities on TMV in vivo, with 50% effective
concentration values ranging from 132.25 to 156.10 MUg/mL. These values are
superior to that of ningnanmycin (281.22 MUg/mL) and suggest that novel 4(3H)
quinazolinone derivatives containing 1,4-pentadien-3-one moiety can effectively
control TMV. Evaluation of the antiviral properties in field studies and the
mechanisms underlying the enhanced antiviral activities of these derivatives are
an interesting topic for future investigation.
PMID- 25112465
TI - Use of combination antihypertensive therapy initiation in older Americans without
prevalent cardiovascular disease.
AB - OBJECTIVES: To describe new users of antihypertensive medications and identify
predictors of combination therapy initiation in older Americans. DESIGN:
Retrospective observational cohort study. SETTING: Population-based study using
U.S. Medicare fee-for-service healthcare claims (2007-2010). PARTICIPANTS:
Medicare beneficiaries aged 65 and older with no recent diagnoses, procedures, or
medications for cardiovascular disease who newly initiated an antihypertensive
therapy (n = 275,493; 210,605 initiated monotherapy, 64,888 initiated combination
therapy). MEASUREMENTS: Multivariable Poisson regression was used to assess
factors associated with initiation of combination therapy versus monotherapy,
including participant characteristics, prescriber characteristics, and
participant encounters with the healthcare system. RESULTS: Initiation of
combination therapy increased from 21.9% in 2007 to 24.7% in 2010. The most
frequently initiated combinations were angiotensin-converting enzyme inhibitors
with thiazide (29.7%) and angiotensin II receptor antagonists with thiazide
(18.7%). Blacks (prevalence ratio (PR) = 1.48, 95% confidence interval (CI) =
1.45-1.51 vs. whites), individuals seeing a generalist (PR = 1.10, 95% CI = 1.07
1.14), individuals seeing more than one doctor (PR = 3.38, 95% CI = 3.33-3.44),
and participants with no pharmacy claims in the previous 6 months (PR = 1.34, 95%
CI = 1.30-1.37 vs. >=3 unique drug classes) were more likely to initiate
combination therapy, whereas those who had more outpatient visits in the previous
12 months were less likely to initiate combination therapy (per five visits, PR =
0.82, 95% CI = 0.80-0.83). CONCLUSION: Nearly one in four new users of
antihypertensive medications aged 65 and older started treatment with combination
therapy. Blacks, individuals living in the south, and those with fewer outpatient
physician office visits were more likely to initiate combination therapy. Further
research is needed to determine whether this approach to managing hypertension is
being well targeted to individuals who will require combination treatment.
PMID- 25112467
TI - The effect of proinflammatory cytokines on IL-17RA expression in NSCLC.
AB - Interleukin-17 receptor (IL-17RA) is essential for proinflammatory cytokine IL-17
mediated pathogenesis of various tumors. IL-17RA is upregulated by some
proinflammatory cytokines such as IL-21 and IL-15 and downregulated by IL-2,
while the effect of IL-1beta, IL-6, IL-8, TNF-alpha on IL-17RA expression in non
small cell lung caner (NSCLC) remains unknown. Our findings revealed that IL-17RA
mRNA was increased in NSCLC tissues compared with the corresponding peritumor
tissues (P = 0.0039) and high expression of IL-17RA protein in human NSCLC
tissues was significantly associated with histological subtype, primary tumor
size and clinical stages (P = 0.033, 0.033 and 0.011, respectively). IL-17RA mRNA
expression was positively related to IL-1beta, IL-6, IL-8, TNF-alpha mRNA
expression (P = 0.013, 0.0001, 0.002 and 0.010 respectively) in NSCLC tissues.
Furthermore, IL-1beta, IL-6, IL-8, TNF-alpha upregulated IL-17RA mRNA and protein
in A549 and H460 cells (all P < 0.05). It is suggested that IL-1beta, IL-6, IL-8,
TNF-alpha promoted IL-17RA expression in NSCLC and they may involve in IL-17RA
signaling in NSCLC.
PMID- 25112468
TI - Outcomes of surgical treatment for gastric cancer patients: 11-year experience of
a Chinese high-volume hospital.
AB - Gastric cancer is one of the leading causes of cancer-related deaths worldwide.
We report our experience with surgery-related parameters and survival outcomes at
a single Chinese center. This study analyzed patients following gastric resection
between 2000 and 2010, and overall survival was the primary end point. In this
study, 1,936 patients who underwent gastrectomy were collected from 2000 to 2010.
Curative gastrectomy (R0 resection) was performed in 86.6 % of patients. D1/D1+
lymphadenectomy was frequently performed from 2000 to 2005, and the proportion of
D2/D2+ lymphadenectomy increased after 2006. The number of harvested lymph nodes
was 10.1 +/- 6.0 in 2000 and increased to 28.0 +/- 10.5 in 2010. Serosa-invasive
lesions (pT4) accounted for 67.9 % of all cases. The 1-year overall survival
(OS), 2-year OS, and 3-year OS rates were 89, 74, and 63 %, respectively.
Multivariate analysis identified R status, tumor location, macroscopic type, and
tumor stage (pT stage and pN stage) as the independent risk factors for overall
survival. The prognosis of gastric cancer patients in China remains dismal. To
improve the survival outcomes, further efforts toward early detection and multi
disciplinary treatment are needed.
PMID- 25112470
TI - Dyspnoea and comorbidity contribute to anxiety and depression in interstitial
lung disease.
AB - BACKGROUND AND OBJECTIVES: Little is known about the prevalence of anxiety in
interstitial lung disease (ILD), and the contributors to depression are not
clear. The aim of this study was to determine the prevalence and predictors of
anxiety and depression in people with ILD. METHODS: One hundred and twenty-four
individuals with ILD (age 64 years (standard deviation 12), 48 idiopathic
pulmonary fibrosis) participated. Anxiety and depression were assessed using the
Hospital Anxiety and Depression Scale to determine likely cases and borderline
cases. Associations with demographic data, respiratory function, 6-min walk and
Modified Medical Research Council Dyspnoea Scale (MMRC) were examined. RESULTS:
The prevalence of anxiety was 31%, with clinically significant anxiety in 12%.
Depression was present in 23% of individuals, with 7% having clinically
significant depression. Independent predictors of anxiety were a higher MMRC
score (P = 0.005, odds ratio (OR) for case 2.60, 95% confidence interval 1.37 to
4.92) and higher nadir SpO2 during walking (P = 0.003, OR for case 1.16, 1.04
1.30). Independent predictors of depression were a higher MMRC score (P = 0.006,
case OR 3.84, 1.25-11.78, borderline case OR 2.44, 1.14-5.19) and a greater
number of comorbidities (P = 0.003, case OR 2.02, 0.97-4.21, borderline case OR
2.26, 1.30-3.93). CONCLUSIONS: Anxiety and depression are present in a
significant minority of individuals with ILD. Dyspnoea and comorbidities are
important contributors that may be amenable to intervention.
PMID- 25112471
TI - NPHS2 variation in Chinese southern infants with late steroid-resistant nephrotic
syndrome.
AB - Abstract NPHS2 mutations are responsible for autosomal recessive familial steroid
resistant nephrotic syndrome (SRNS) with minor glomerular abnormalities or focal
segmental glomerulosclerosis (FSGS), which is characterized by early childhood
onset and rapid progression to chronic renal insufficiency. This gene mutation is
also responsible for an adolescent onset form of autosomal recessive familial
FSGS with heavy proteinuria. Many infants with late steroid-resistant nephrotic
syndrome (late SRNS) are prone to an implicated clinical and therapeutic course.
The etiopathogenesis and the long-term prognosis of late SRNS remain obscure.
Considering the similar steroid resistance between late and initial SRNS,
analysis of NPHS2 variation was performed in 70 sporadic Chinese infants with
late SRNS and 70 controls in the present study to investigate the possible role
of NPHS2 gene in late SRNS. The variation analysis revealed three polymorphisms
(288C > T heterozygous in exon 2, 954T > C heterozygous and homozygous, and 1038A
> G heterozygous in exon 8) in 22 out of 70 patients studied. In conclusion,
NPHS2 gene mutations are not a major cause of chronic renal insufficiency caused
by late SRNS in Chinese southern infants.
PMID- 25112472
TI - Cell and molecular biology of intervertebral disc degeneration: current
understanding and implications for potential therapeutic strategies.
AB - Intervertebral disc degeneration (IDD) is a chronic, complex process associated
with low back pain; mechanisms of its occurrence have not yet been fully
elucidated. Its process is not only accompanied by morphological changes, but
also by systematic changes in its histological and biochemical properties. Many
cellular and molecular mechanisms have been reported to be related with IDD and
to reverse degenerative trends, abnormal conditions of the living cells and
altered cell phenotypes would need to be restored. Promising biological
therapeutic strategies still rely on injection of active substances, gene therapy
and cell transplantation. With advanced study of tissue engineering protocols
based on cell therapy, combined use of seeding cells, bio-active substances and
bio-compatible materials, are promising for IDD regeneration. Recently reported
progenitor cells within discs themselves also hold prospects for future IDD
studies. This article describes the background of IDD, current understanding and
implications of potential therapeutic strategies.
PMID- 25112469
TI - Clinical significance of HuR expression in human malignancy.
AB - Hu-antigen R (HuR) is an RNA-binding protein that regulates the stability,
translation, and nucleus-to-cytoplasm translocation of target mRNAs. The aim of
the present review was to summarize and present the currently available
information in the English literature on HuR expression in various human tumors,
verifying its possible clinical significance. HuR function is directly linked to
its subcellular localization. In normal cells, HuR is mostly localized in the
nucleus, while in malignant cells, an increase in cytoplasmic HuR levels has been
noted, in both cell lines and tissue samples. Moreover, in malignancy, elevated
HuR expression levels and cytoplasmic immunohistochemical pattern have been
correlated with advanced clinicopathological parameters and altered expression
levels of proteins implicated in neoplasia. Additionally, elevated HuR expression
levels and mainly cytoplasmic immunohistochemical pattern were correlated with
decreased patients' survival rate in various human tumors. HuR is a putative drug
target for cancer therapy, since it is expressed ubiquitously in malignant
clinical samples and has an apparently consistent role in tumor formation and
progression.
PMID- 25112473
TI - Towards an informative mutant phenotype for every bacterial gene.
AB - Mutant phenotypes provide strong clues to the functions of the underlying genes
and could allow annotation of the millions of sequenced yet uncharacterized
bacterial genes. However, it is not known how many genes have a phenotype under
laboratory conditions, how many phenotypes are biologically interpretable for
predicting gene function, and what experimental conditions are optimal to
maximize the number of genes with a phenotype. To address these issues, we
measured the mutant fitness of 1,586 genes of the ethanol-producing bacterium
Zymomonas mobilis ZM4 across 492 diverse experiments and found statistically
significant phenotypes for 89% of all assayed genes. Thus, in Z. mobilis, most
genes have a functional consequence under laboratory conditions. We demonstrate
that 41% of Z. mobilis genes have both a strong phenotype and a similar fitness
pattern (cofitness) to another gene, and are therefore good candidates for
functional annotation using mutant fitness. Among 502 poorly characterized Z.
mobilis genes, we identified a significant cofitness relationship for 174. For 57
of these genes without a specific functional annotation, we found additional
evidence to support the biological significance of these gene-gene associations,
and in 33 instances, we were able to predict specific physiological or
biochemical roles for the poorly characterized genes. Last, we identified a set
of 79 diverse mutant fitness experiments in Z. mobilis that are nearly as
biologically informative as the entire set of 492 experiments. Therefore, our
work provides a blueprint for the functional annotation of diverse bacteria using
mutant fitness.
PMID- 25112474
TI - Epoxide-mediated differential packaging of Cif and other virulence factors into
outer membrane vesicles.
AB - Pseudomonas aeruginosa produces outer membrane vesicles (OMVs) that contain a
number of secreted bacterial proteins, including phospholipases, alkaline
phosphatase, and the CFTR inhibitory factor (Cif). Previously, Cif, an epoxide
hydrolase, was shown to be regulated at the transcriptional level by epoxides,
which serve as ligands of the repressor, CifR. Here, we tested whether epoxides
have an effect on Cif levels in OMVs. We showed that growth of P. aeruginosa in
the presence of specific epoxides but not a hydrolysis product increased Cif
packaging into OMVs in a CifR-independent fashion. The outer membrane protein,
OprF, was also increased under these conditions, but alkaline phosphatase
activity was not significantly altered. Additionally, we demonstrated that OMV
shape and density were affected by epoxide treatment, with two distinct vesicle
fractions present when cells were treated with epibromohydrin (EBH), a model
epoxide. Vesicles isolated from the two density fractions exhibited different
protein profiles in Western blotting and silver staining. We have shown that a
variety of clinically or host-relevant treatments, including antibiotics, also
alter the proteins packaged in OMVs. Proteomic analysis of purified OMVs followed
by an analysis of transposon mutant OMVs yielded mutants with altered vesicle
packaging. Finally, epithelial cell cytotoxicity was reduced in the vesicles
formed in the presence of EBH, suggesting that this epoxide alters the function
of the OMVs. Our data support a model whereby clinically or host-relevant signals
mediate differential packaging of virulence factors in OMVs, which results in
functional consequences for host-pathogen interactions.
PMID- 25112475
TI - The disulfide bonding system suppresses CsgD-independent cellulose production in
Escherichia coli.
AB - The bacterial extracellular matrix encases cells and protects them from host
related and environmental insults. The Escherichia coli master biofilm regulator
CsgD is required for the production of the matrix components curli and cellulose.
CsgD activates the diguanylate cyclase AdrA, which in turn stimulates cellulose
production through cyclic di-GMP (c-di-GMP). Here, we identified and
characterized a CsgD- and AdrA-independent cellulose production pathway that was
maximally active when cultures were grown under reducing conditions or when the
disulfide bonding system (DSB) was compromised. The CsgD-independent cellulose
activation pathway was dependent on a second diguanylate cyclase, called YfiN. c
di-GMP production by YfiN was repressed by the periplasmic protein YfiR, and
deletion of yfiR promoted CsgD-independent cellulose production. Conversely, when
YfiR was overexpressed, cellulose production was decreased. Finally, we found
that YfiR was oxidized by DsbA and that intraprotein YfiR disulfide bonds
stabilized YfiR in the periplasm. Altogether, we showed that reducing conditions
and mutations in the DSB system caused hyperactivation of YfiN and subsequent
CsgD-independent cellulose production.
PMID- 25112476
TI - Mutations in the primary sigma factor sigmaA and termination factor rho that
reduce susceptibility to cell wall antibiotics.
AB - Combinations of glycopeptides and beta-lactams exert synergistic antibacterial
activity, but the evolutionary mechanisms driving resistance to both antibiotics
remain largely unexplored. By repeated subculturing with increasing vancomycin
(VAN) and cefuroxime (CEF) concentrations, we isolated an evolved strain of the
model bacterium Bacillus subtilis with reduced susceptibility to both
antibiotics. Whole-genome sequencing revealed point mutations in genes encoding
the major sigma factor of RNA polymerase (sigA), a cell shape-determining protein
(mreB), and the rho termination factor (rho). Genetic-reconstruction experiments
demonstrated that the G-to-C substitution at position 336 encoded by sigA
(sigA(G336C)), in the domain that recognizes the -35 promoter region, is
sufficient to reduce susceptibility to VAN and works cooperatively with the
rho(G56C) substitution to increase CEF resistance. Transcriptome analyses
revealed that the sigA(G336C) substitution has wide-ranging effects, including
elevated expression of the general stress sigma factor (sigma(B)) regulon, which
is required for CEF resistance, and decreased expression of the glpTQ genes,
which leads to fosfomycin (FOS) resistance. Our findings suggest that mutations
in the core transcriptional machinery may facilitate the evolution of resistance
to multiple cell wall antibiotics.
PMID- 25112478
TI - Enzymes involved in a novel anaerobic cyclohexane carboxylic acid degradation
pathway.
AB - The anaerobic degradation of cyclohexane carboxylic acid (CHC) has so far been
studied only in Rhodopseudomonas palustris, in which CHC is activated to
cyclohexanoyl coenzyme A (cyclohexanoyl-CoA [CHCoA]) and then dehydrogenated to
cyclohex-1-ene-1-carboxyl-CoA (CHeneCoA). This intermediate is further degraded
by reactions of the R. palustris-specific benzoyl-CoA degradation pathway of
aromatic compounds. However, CHeneCoA is not an intermediate in the degradation
of aromatic compounds in all other known anaerobic bacteria; consequently,
degradation of CHC was mostly unknown in anaerobic bacteria. We identified a
previously unknown CHC degradation pathway in the Fe(III)-reducing Geobacter
metallireducens by determining the following CHC-induced in vitro activities: (i)
the activation of CHC to CHCoA by a succinyl-CoA:CHC CoA transferase, (ii) the
1,2-dehydrogenation of CHCoA to CHeneCoA by CHCoA dehydrogenase, and (iii) the
unusual 1,4-dehydrogenation of CHeneCoA to cyclohex-1,5-diene-1-carboxyl-CoA.
This last represents a previously unknown joint intermediate of the CHC and
aromatic compound degradation pathway in bacteria other than R. palustris. The
enzymes catalyzing the three reactions were purified and characterized as
specific enzymes after heterologous expression of the encoding genes.
Quantitative reverse transcription-PCR revealed that expression of these genes
was highly induced during growth with CHC but not with benzoate. The newly
identified CHC degradation pathway is suggested to be present in nearly all CHC
degrading anaerobic bacteria, including denitrifying, Fe(III)-reducing, sulfate
reducing, and fermenting bacteria. Remarkably, all three CHC degradation pathways
always link CHC catabolism to the catabolic pathways of aromatic compounds. We
propose that the capacity to use CHC as a carbon source evolved from already
existing aromatic compound degradation pathways.
PMID- 25112479
TI - Competence for genetic transformation in Streptococcus pneumoniae: mutations in
sigmaA bypass the comW requirement.
AB - Competence for genetic transformation in the genus Streptococcus depends on an
alternative sigma factor, sigma(X), for coordinated synthesis of 23 proteins,
which together establish the X state by permitting lysis of incompetent
streptococci, uptake of DNA fragments, and integration of strands of that DNA
into the resident genome. Initiation of transient accumulation of high levels of
sigma(X) is coordinated between cells by transcription factors linked to peptide
pheromone signals. In Streptococcus pneumoniae, elevated sigma(X) is insufficient
for development of full competence without coexpression of a second competence
specific protein, ComW. ComW, shared by eight species in the Streptococcus mitis
and Streptococcus anginosus groups, is regulated by the same pheromone circuit
that controls sigma(X), but its role in expression of the sigma(X) regulon is
unknown. Using the strong, but not absolute, dependence of transformation on comW
as a selective tool, we collected 27 independent comW bypass mutations and mapped
them to 10 single-base transitions, all within rpoD, encoding the primary sigma
factor subunit of RNA polymerase, sigma(A). Eight mapped to sites in rpoD region
4 that are implicated in interaction with the core beta subunit, indicating that
ComW may act to facilitate competition of the alternative sigma factor sigma(X)
for access to core polymerase.
PMID- 25112477
TI - Serotype-converting bacteriophage SfII encodes an acyltransferase protein that
mediates 6-O-acetylation of GlcNAc in Shigella flexneri O-antigens, conferring on
the host a novel O-antigen epitope.
AB - Shigella flexneri O-antigen is an important and highly variable cell component
presented on the outer leaflet of the outer membrane. Most Shigella flexneri
bacteria share an O-antigen backbone composed of ->2)-alpha-L-Rhap(III)-(1->2)
alpha-L-Rhap(II)-(1->3)-alpha-L-Rhap(I)-(1->3)-beta-D-GlcpNAc-(1-> repeats, which
can be modified by adding various chemical groups to different sugars, giving
rise to diverse O-antigen structures and, correspondingly, to various serotypes.
The known modifications include glucosylation on various sugar residues, O
acetylation on Rha(I) or/and Rha(III), and phosphorylation with
phosphoethanolamine on Rha(II) or/and Rha(III). Recently, a new O-antigen
modification, namely, O-acetylation at position 6 of N-acetylglucosamine
(GlcNAc), has been identified in S. flexneri serotypes 2a, 3a, Y, and Yv. In this
study, the genetic basis of the 6-O-acetylation of GlcNAc in S. flexneri was
elucidated. An O-acyltransferase gene designated oacD was found to be responsible
for this modification. The oacD gene is carried on serotype-converting
bacteriophage SfII, which is integrated into the host chromosome by lysogeny to
form a prophage responsible for the evolvement of serotype 2 of S. flexneri. The
OacD-mediated 6-O-acetylation also occurs in some other S. flexneri serotypes
that carry a cryptic SfII prophage with a dysfunctional gtr locus for type II
glucosylation. The 6-O-acetylation on GlcNAc confers to the host a novel O
antigen epitope, provisionally named O-factor 10. These findings enhance our
understanding of the mechanisms of the O-antigen variation and enable further
studies to understand the contribution of the O-acetylation to the antigenicity
and pathogenicity of S. flexneri.
PMID- 25112480
TI - Functional and structural analysis of HicA3-HicB3, a novel toxin-antitoxin system
of Yersinia pestis.
AB - The mechanisms involved in the virulence of Yersinia pestis, the plague pathogen,
are not fully understood. In previous research, we found that a Y. pestis mutant
lacking the HicB3 (YPO3369) putative orphan antitoxin was attenuated for
virulence in a murine model of bubonic plague. Toxin-antitoxin systems (TASs) are
widespread in prokaryotes. Most bacterial species possess many TASs of several
types. In type II TASs, the toxin protein is bound and neutralized by its cognate
antitoxin protein in the cytoplasm. Here we identify the hicA3 gene encoding the
toxin neutralized by HicB3 and show that HicA3-HicB3 constitutes a new functional
type II TAS in Y. pestis. Using biochemical and mutagenesis-based approaches, we
demonstrate that the HicA3 toxin is an RNase with a catalytic histidine residue.
HicB3 has two functions: it sequesters and neutralizes HicA3 by blocking its
active site, and it represses transcription of the hicA3B3 operon. Gel shift
assays and reporter fusion experiments indicate that the HicB3 antitoxin binds to
two operators in the hicA3B3 promoter region. We solved the X-ray structures of
HicB3 and the HicA3-HicB3 complex; thus, we present the first crystal structure
of a TA complex from the HicAB family. HicB3 forms a tetramer that can bind two
HicA3 toxin molecules. HicA3 is monomeric and folds as a double-stranded-RNA
binding domain. The HicB3 N-terminal domain occludes the HicA3 active site,
whereas its C-terminal domain folds as a ribbon-helix-helix DNA-binding motif.
PMID- 25112483
TI - 3,6-Epidioxy-1,10-bisaboladiene inhibits G1 -specific transcription through
Swi4/Swi6 and Mbp1/Swi6 via the Hog1 stress pathway in yeast.
AB - 3,6-Epidioxy-1,10-bisaboladiene (EDBD), a bisabolane sesquiterpene endoperoxide
compound, was previously isolated from Cacalia delphiniifolia and C. hastata in
northern Japan. EDBD has cytotoxic effects and induces apoptosis via
phosphorylation of p38 mitogen-activated protein kinase in human promyelocytic
leukemia HL60 cells. However, the mechanism of action of EDBD has not yet been
fully elucidated. In this study, we examined the molecular mechanisms of EDBD in
the budding yeast Saccharomyces cerevisiae. EDBD arrested the growth of S.
cerevisiae cells by suppressing progression from the G1 phase to the S phase and
from the G2 phase to the M phase. Moreover, biochemical and genetic analyses
revealed that EDBD activated environmental stress-response pathways involving
Hog1 and affected Cln3/G1 cyclin activity, thereby inhibiting the expression of
SCB-binding factor and MCB-binding factor target genes. Our results provided
important insights into the functions of EDBD in tumor cells and may facilitate
the development of EDBD-based antitumor therapies. STRUCTURED DIGITAL ABSTRACT:
*Swi4 physically interacts with Swi6 by anti tag coimmunoprecipitation (View
interaction).
PMID- 25112484
TI - The association between vibration and vascular injury in rheumatic diseases: a
review of the literature.
AB - Vascular manifestations can be seen early in the pathogenesis of inflammatory
rheumatic diseases. Animal experiments, laboratory and clinical findings
indicated that acute or long-term vibration exposure can induce vascular
abnormalities. Recent years, in addition to Raynaud's phenomenon (RP), vibration
as a risk factor for other rheumatic diseases has also received corresponding
considered. This review is concentrated upon the role of vibration in the disease
of systemic sclerosis (SSc). In this review, we are going to discuss the main
mechanisms which are thought to be important in pathophysiology of vascular
injury under the three broad headings of "vascular", "neural" and
"intravascular". Aspects on the vibration and vascular inflammation are briefly
discussed. And the epidemiological studies related to vibration studies in SSc
and other rheumatic diseases are taken into account.
PMID- 25112481
TI - A comparison of the effectiveness of physical activity and sedentary behaviour
interventions in reducing sedentary time in adults: a systematic review and meta
analysis of controlled trials.
AB - The objective of this study was to systematically review the literature and
compare the effectiveness of controlled interventions with a focus on physical
activity (PA) and/or sedentary behaviours (SBs) for reducing sedentary time in
adults. Six electronic databases were searched to identify all studies that
examined the effects of interventions that targeted PA and/or SBs and that
reported on changes in SBs (sedentary, sitting or television time). A qualitative
synthesis was performed for all studies, and meta-analyses conducted among
studies with mean differences (min/d) of sedentary time. PROSPERO:
CRD42014006535. Sixty-five controlled studies met inclusion criteria; 33 were
used in the meta-analyses. Interventions with a focus on PA or that included a PA
and SB component produced less consistent findings and generally resulted in
modest reductions in sedentary time (PA: standardized mean differences [SMD] =
0.22 [95% confidence interval {CI}: -0.35, -0.10], PA+SB: SMD= -0.37 [95% CI:
0.69, -0.05]). Moderate quality evidence from the randomized controlled trial
meta-analysis coupled with the qualitative synthesis provides consistent evidence
that large and clinically meaningful reductions in sedentary time can be expected
from interventions with a focus on reducing SBs (SMD= -1.28 [95% CI: -1.68,
0.87] ). There is evidence to support the need for interventions to include a
component focused on reducing SBs in order to generate clinically meaningful
reductions in sedentary time.
PMID- 25112485
TI - The relationship between daily urinary sodium excretion and metabolic syndrome in
patients with kidney transplantation.
AB - BACKGROUND: The aim of this study was to determine whether there is a
relationship between daily urinary sodium excretion and metabolic syndrome in
kidney transplantation patients. MATERIAL AND METHODS: This cross-sectional study
included 76 adult renal transplantation recipients. To calculate urinary sodium
excretion, 24-h urine samples were collected. Metabolic syndrome was diagnosed
according to Adult Treatment Panel III (ATP III) criteria updated in a statement
from the American Heart Association (AHA)/National Heart, Lung, and Blood
Institute (NHLBI) in 2005. RESULTS: Mean age of the 76 patients was 38 +/- 10
years; 21 of the 76 patients were female. Metabolic syndrome was found in 52
(68.4%) of the 76 renal transplantation patients. Mean daily urinary sodium
excretion was 190 +/- 102 mmol/day, which is equal to a salt intake of 11.1
g/day. Daily urinary sodium excretion was significantly higher in patients with
metabolic syndrome compared to those without metabolic syndrome (209 +/- 112
mmol/day and 150 +/- 62 mmol/day, respectively, p: 0.005). Daily urinary sodium
excretion correlated with diastolic blood pressure (r: 0.254, p: 0.028), serum
glucose concentration (r: 0.446, p: <0.001), and creatinine clearance (r: 478, p:
<0.001). In addition, although there was no significant correlation between daily
urinary sodium excretion and systolic blood pressure, the statistical
significance was borderline (r: 0.221, p: 0.056). CONCLUSIONS: There is a
significant relationship between daily urinary sodium excretion and metabolic
syndrome in renal transplant recipients. The Turkish kidney transplantation
patients consume a great amount of salt and salt intake is positively correlated
with blood pressure.
PMID- 25112486
TI - Factors Associated With Hospitalizations Among HIV-Infected Adults in the United
States: Review of the Literature.
AB - Although improving health outcomes in human immunodeficiency virus (HIV)-infected
persons has been identified as a national priority, little is known about the
factors associated with hospitalizations of HIV-infected persons in the highly
active antiretroviral therapy (HAART) era. Since the introduction of HAART in
1996, there has been a dramatic increase in the life expectancy of HIV-infected
persons. However, aging and the long term use of HIV medications have led to an
increased incidence of chronic, non-HIV-related illnesses. To improve patient
outcomes, the factors that contribute to co-morbidities in HIV-infected persons
need to be identified. As a first step, we will summarize the current literature
on causes and contributing factors of hospitalizations in adults infected with
HIV in the HAART era.
PMID- 25112487
TI - Noninvasive prenatal testing.
AB - Noninvasive prenatal testing (NIPT) refers to recently developed genetic tests of
the maternal serum that allow higher detection rates of trisomy 21 and other
chromosomal aneuploidies in high-risk pregnancies. Noninvasive prenatal test
analyzes cell-free DNA (cfDNA) in the maternal serum. Approximately 3% to 15% of
cfDNA in the maternal blood is of fetal origin. Analysis of cfDNA can help
identify fetuses affected with trisomy 21 and several other fetal aneuploidies.
Testing can be performed after 9 to 10 weeks' gestation and has a higher
sensitivity and specificity for trisomy 21 than other aneuploidy screening test.
Noninvasive prenatal test has been studied and validated in singleton pregnancies
at risk for trisomy 21 secondary to advanced maternal age, an abnormal serum
screen, personal or family history of aneuploidy, or abnormal ultrasound
findings, if these are suggestive of trisomy 13, 18, or 21. The utilization of
NIPT for genetic screening has increased rapidly since introduction of the first
clinical test in October 2011. Currently, there are limitations to NIPT including
the possibility of test failure (2.6%-5.4%) and the focus on only the common
trisomies. Noninvasive prenatal test is a screening test, and both false-positive
(0.2%-1%) and false-negative results can occur. As the technology for NIPT is
further evaluated, this test is likely to be increasingly used for prenatal
screening. This review provides the obstetric clinician with an update of the
current issues concerning NIPT.
PMID- 25112488
TI - The impact of preoperative gonadotropin-releasing hormone agonist treatment on
women with uterine fibroids: a meta-analysis.
AB - AIM: The objectives of this study were to evaluate the efficacy of gonadotropin
releasing hormone agonist (GnRHa) treatment before surgery for women with uterine
fibroids and to explore potential factors predicting the pooled effect sizes.
METHODS: A meta-analysis was performed from published randomized controlled
trials using the random effects model. The efficacy of preoperative treatment
with GnRHa was investigated according to volume measurements of fibroid tumors,
postoperative complications, myoma recurrence, and changes in fertility.
Metaregression and subgroup analysis were used to identify potential predictors
of the effect sizes. RESULTS: A total of 26 studies were selected for the meta
analysis. Preoperative GnRHa therapy for women with uterine fibroids was
associated with a smaller preoperative volume of fibroid tumors, increased
hemoglobin and hematocrit levels, reductions in preoperative pelvic symptoms and
the vertical incision rate, and a higher proportion of patients undergoing a
vaginal procedure. No differences were observed in postoperative complications,
myoma recurrence, and changes in fertility in the GnRHa-treated patients compared
with patients treated with placebo or alternative clinical agents. The
metaregression suggested that age, the duration of GnRHa treatment, the type of
control group, and the type of surgery were important predictors of the efficacy
of preoperative GnRHa treatment. CONCLUSIONS: Preoperative GnRHa treatment for
women with uterine fibroids reduces preoperative fibroid size and increases
hemoglobin and hematocrit levels. Gonadotropin-releasing hormone agonist
pretreatment reduces preoperative pelvic symptoms and the rate of vertical
incision and results in a higher chance of patients to receive a vaginal
procedure, without significant difference in postoperative complications when
comparing with other preoperative treatments. The patients' age, duration of
GnRHa treatment, agents selected as control, and types of surgical procedures
serve as predictors of the efficacy of preoperative GnRHa treatment.
PMID- 25112489
TI - Definition and epidemiology of unexplained infertility.
AB - The diagnosis of unexplained infertility can be made only after excluding common
causes of infertility using standard fertility investigations,which include semen
analysis, assessment of ovulation, and tubal patency test. These tests have been
selected as they have definitive correlation with pregnancy. It is estimated that
a standard fertility evaluation will fail to identify an abnormality in
approximately 15% to 30% of infertile couples. The reported incidence of such
unexplained infertility varies according to the age and selection criteria in the
study population. We conducted a review of the literature via MEDLINE. Articles
were limited to English-language, human studies published between 1950 and 2013.
Since first coined more than 50 years ago, the term unexplained infertility has
been a subject of debate. Although additional investigations are reported to
explain or define other causes of infertility, these have high false-positive
results and therefore cannot be recommended for routine clinical practice.
Couples with unexplained infertility might be reassured that even after 12 months
of unsuccessful attempts, 50% will conceive in the following 12 months and
another 12% in the year after.
PMID- 25112491
TI - Shear stress and VEGF enhance endothelial differentiation of human adipose
derived stem cells.
AB - Herein we combine chemical and mechanical stimulation to investigate the effects
of vascular endothelial growth factor (VEGF) and physiological shear stress in
promoting the differentiation human adipose derived stem cells (ADSCs) into
endothelial cells. ADSCs were isolated and characterized; endothelial
differentiation was promoted by culturing confluent cells in 50 ng/ml VEGF under
physiological shear stress for up to 14 days. Afterwards, endothelial cells were
seeded onto collagen or acellular aortic valve matrices and exposed to four
culture conditions: shear stress + VEGF; shear stress - VEGF; static + VEGF and
static - VEGF. After 7 days, phenotype was investigated. ADSCs subjected to shear
stress and VEGF express a comprehensive range of specific endothelial markers
(vWF, eNOS and FLT-1 after 7 days and CD31, FLk-1 and VE-cadherin after 14 days)
and maintain the phenotype when seeded onto scaffolds. Our protocol proved to be
an efficient source of endothelial-like cells for tissue engineering based on
autologous ADSC.
PMID- 25112492
TI - Identifying determinants of care for tailoring implementation in chronic
diseases: an evaluation of different methods.
AB - BACKGROUND: The tailoring of implementation interventions includes the
identification of the determinants of, or barriers to, healthcare practice.
Different methods for identifying determinants have been used in implementation
projects, but which methods are most appropriate to use is unknown. METHODS: The
study was undertaken in five European countries, recommendations for a different
chronic condition being addressed in each country: Germany (polypharmacy in
multimorbid patients); the Netherlands (cardiovascular risk management); Norway
(depression in the elderly); Poland (chronic obstructive pulmonary disease-
COPD); and the United Kingdom (UK) (obesity). Using samples of professionals and
patients in each country, three methods were compared directly: brainstorming
amongst health professionals, interviews of health professionals, and interviews
of patients. The additional value of discussion structured through reference to a
checklist of determinants in addition to brainstorming, and determinants
identified by open questions in a questionnaire survey, were investigated
separately. The questionnaire, which included closed questions derived from a
checklist of determinants, was administered to samples of health professionals in
each country. Determinants were classified according to whether it was likely
that they would inform the design of an implementation intervention (defined as
plausibly important determinants). RESULTS: A total of 601 determinants judged to
be plausibly important were identified. An additional 609 determinants were
judged to be unlikely to inform an implementation intervention, and were
classified as not plausibly important. Brainstorming identified 194 of the
plausibly important determinants, health professional interviews 152, patient
interviews 63, and open questions 48. Structured group discussion identified 144
plausibly important determinants in addition to those already identified by
brainstorming. CONCLUSIONS: Systematic methods can lead to the identification of
large numbers of determinants. Tailoring will usually include a process to
decide, from all the determinants that are identified, those to be addressed by
implementation interventions. There is no best buy of methods to identify
determinants, and a combination should be used, depending on the topic and
setting. Brainstorming is a simple, low cost method that could be relevant to
many tailored implementation projects.
PMID- 25112493
TI - Vitamin D insufficiency and abnormal hemoglobin a1c in black and white older
persons.
AB - BACKGROUND: Although vitamin D has been mechanistically linked to insulin
secretion and sensitivity, it remains unclear whether low 25-hydroxyvitamin D
levels confer an increased risk of impaired glucose metabolism. We evaluated the
relationship between vitamin D insufficiency (25-hydroxyvitamin D < 20ng/mL) and
abnormal hemoglobin A1c (A1c) (>=6.5%) in community-dwelling older persons and
examined whether this relationship differed according to race. METHODS:
Participants were 2,193 persons of age 70-79 years at Year 1 (52% women; 37%
black) in the Health, Aging, and Body Composition study who had clinic visits at
Years 2 and 4. Logistic regression analyses, adjusted for potential confounders,
were used to evaluate the association between vitamin D insufficiency and
abnormal A1c 2 years later. Interaction of race and vitamin D insufficiency was
tested. RESULTS: A total of 665 (30%) and 301 (14%) of the participants had
vitamin D insufficiency at Year 2 and abnormal A1c at Year 4, respectively. After
controlling for demographics, other potential confounders, and diabetes status at
Year 4 (n = 477 diabetics), we found that vitamin D insufficiency was associated
with an increased likelihood of having abnormal A1c (odds ratio = 1.56; 95% CI:
1.03-2.37). We also found that this relationship persisted among the 1,765
participants without diabetes in Year 2 (odds ratio = 2.33; 95% CI: 1.00-5.40).
Findings did not differ by race. CONCLUSIONS: Vitamin D insufficiency was
associated with abnormal A1c levels among black and white older persons
independent of diabetes status. Future studies are needed to establish the
temporal relationship between vitamin D and A1c in diverse samples of older
persons.
PMID- 25112495
TI - The assessment of general well-being using spontaneous burrowing behaviour in a
short-term model of chemotherapy-induced mucositis in the rat.
AB - Mucositis is a common and serious side-effect experienced by cancer patients
during treatment with chemotherapeutic agents. Consequently, programmes of
research focus on the elucidation of novel therapeutics for alleviation of
mucositis symptoms, and these frequently use animal models. However, although
these models are assumed to be painful and distressing to the animal, endpoints
are difficult to determine. The aim of this study was to evaluate whether a
change in burrowing behaviour could provide an indication of disease onset and
potentially be applied as a humane endpoint. Baseline burrowing behaviour was
measured in healthy animals on three occasions by determining the weight of
gravel displaced from a hollow tube. Mucositis was then induced in the same
animals by intraperitoneal injection of 5-fluorouracil (150 mg/kg) and burrowing
behaviour recorded over three consecutive days. Standard measures of disease
progression, including body weight loss and clinical score, were also made. The
presence of mucositis was confirmed at necropsy by findings of decreased duodenal
and colon lengths, and reduced liver, spleen and thymus weights in comparison
with non-treated control animals. Histological score of the jejunum and ileum was
also significantly increased. Mucositis onset coincided with a decrease in mean
burrowing behaviour which was progressive, however this result did not achieve
statistical significance (P = 0.66).We conclude that burrowing may be a useful
indicator of inflammation in the mucositis model, although this requires further
characterization. Pre-selection of animals into treatment groups based on their
prior burrowing performance should be pursued in further studies.
PMID- 25112496
TI - Alkaline phosphatases in microbialites and bacterioplankton from Alchichica soda
lake, Mexico.
AB - Dissolved organic phosphorus utilization by different members of natural
communities has been closely linked to microbial alkaline phosphatases whose
affiliation and diversity is largely unknown. Here we assessed genetic diversity
of bacterial alkaline phosphatases phoX and phoD, using highly diverse microbial
consortia (microbialites and bacterioplankton) as study models. These microbial
consortia are found in an oligo-mesotrophic soda lake with a particular
geochemistry, exhibiting a low calcium concentration and a high Mg : Ca ratio
relative to seawater. In spite of the relative low calcium concentration in the
studied system, our results highlight the diversity of calcium-based
metallophosphatases phoX and phoD-like in heterotrophic bacteria of microbialites
and bacterioplankton, where phoX was the most abundant alkaline phosphatase
found. phoX and phoD-like phylotypes were more numerous in microbialites than in
bacterioplankton. A larger potential community for DOP utilization in
microbialites was consistent with the TN : TP ratio, suggesting P limitation
within these assemblages. A cross-system comparison indicated that diversity of
phoX in Lake Alchichica was similar to that of other aquatic systems with a
naturally contrasting ionic composition and trophic state, although no phylotypes
were shared among systems.
PMID- 25112494
TI - Enhanced somatosensory feedback reduces prefrontal cortical activity during
walking in older adults.
AB - BACKGROUND: The coordination of steady state walking is relatively automatic in
healthy humans, such that active attention to the details of task execution and
performance (controlled processing) is low. Somatosensation is a crucial input to
the spinal and brainstem circuits that facilitate this automaticity. Impaired
somatosensation in older adults may reduce automaticity and increase controlled
processing, thereby contributing to deficits in walking function. The primary
objective of this study was to determine if enhancing somatosensory feedback can
reduce controlled processing during walking, as assessed by prefrontal cortical
activation. METHODS: Fourteen older adults (age 77.1+/-5.56 years) with mild
mobility deficits and mild somatosensory deficits participated in this study.
Functional near-infrared spectroscopy was used to quantify metabolic activity
(tissue oxygenation index, TOI) in the prefrontal cortex. Prefrontal activity and
gait spatiotemporal data were measured during treadmill walking and overground
walking while participants wore normal shoes and under two conditions of enhanced
somatosensation: wearing textured insoles and no shoes. RESULTS: Relative to
walking with normal shoes, textured insoles yielded a bilateral reduction of
prefrontal cortical activity for treadmill walking (DeltaTOI = -0.85 and -1.19
for left and right hemispheres, respectively) and for overground walking
(DeltaTOI = -0.51 and -0.66 for left and right hemispheres, respectively).
Relative to walking with normal shoes, no shoes yielded lower prefrontal cortical
activity for treadmill walking (DeltaTOI = -0.69 and -1.13 for left and right
hemispheres, respectively), but not overground walking. CONCLUSIONS: Enhanced
somatosensation reduces prefrontal activity during walking in older adults. This
suggests a less intensive utilization of controlled processing during walking.
PMID- 25112498
TI - Bloom of the cyanobacterium Moorea bouillonii on the gorgonian coral Annella
reticulata in Japan.
AB - Coral populations are in decline due to environmental changes and biological
attacks by predators and infectious diseases. Here, we report a localized bloom
of the benthic filamentous cyanobacterium Moorea bouillonii (formerly Lyngbya
bouillonii) observed exclusively on the gorgonian (sea fan) coral Annella
reticulata at around 20 m depth in Japan. The degree of infection has reached 26%
among different sizes of Annella colonies. Thick and continuous growth of Moorea
may be sustained partly by symbiotic alpheid shrimp, which affix Moorea filaments
to gorgonian corals for use as food and shelter. Most filaments get entangled on
the coral colony, some penetrate into the stem of the coral with a swollen end
like a root hair, which appears to function as an anchor in Annella. In addition
to the cyanobacterium-shrimp interaction, the new trait of anchoring by the
cyanobacterium into gorgonian coral may contribute to persistence of this bloom.
PMID- 25112497
TI - Perceptions of, attitudes towards and barriers to male involvement in newborn
care in rural Ghana, West Africa: a qualitative analysis.
AB - BACKGROUND: Male involvement in various health practices is recognized as an
important factor in improving maternal and child health outcomes. Male
involvement interventions involve men in a variety of ways, at varying levels of
inclusion and use a range of outcome measures. There is little agreement on how
male involvement should be measured and some authors contend that male
involvement may actually be detrimental to women's empowerment and autonomy. Few
studies explore the realities, perceptions, determinants and efficacy of male
involvement in newborn care, especially in African contexts. METHODS: Birth
narratives of recent mothers (n = 25), in-depth interviews with recent fathers (n
= 12) and two focus group discussions with fathers (n = 22) were conducted during
the formative research phase of a community-based newborn care trial. Secondary
analysis of this qualitative data identified emergent themes and established
overall associations related to male involvement, newborn care and household
roles in a rural African setting. RESULTS: Data revealed that gender dictates
many of the perceptions and politics surrounding newborn care in this context.
The influence of mother-in-laws and generational power dynamics were also
identified as significant. Women alone perform almost all tasks related to
newborn care whereas men take on the traditional responsibilities of economic
providers and decision makers, especially concerning their wives' and children's
health. Most men were interested in being more involved in newborn care but
identified barriers to increased involvement, many of which related to gendered
and generational divisions of labour and space. CONCLUSIONS: Men defined
involvement in a variety of ways, even if they were not physically involved in
carrying out newborn care tasks. Some participant comments revealed potential
risks of increasing male involvement suggesting that male involvement alone
should not be an outcome in future interventions. Rather, the effect of male
involvement on women's autonomy, the dynamics of senior women's influence and
power and the real impact on health outcomes should be considered in intervention
design and implementation. Any male involvement intervention should integrate a
detailed understanding of context and strategies to include men in maternal and
child health should be mutually empowering for both women and men.
PMID- 25112499
TI - Embryogenesis of Heliconius erato (Lepidoptera, Nymphalidae): a contribution to
the anatomical development of an evo-devo model organism.
AB - This study reports on the embryogenesis of Heliconius erato phyllis between
blastoderm formation and the prehatching larval stage. Syncytial blastoderm
formation occurred approximately 2 h after egg laying (AEL) and at about 4 h, the
cellular blastoderm was formed. The germ band arose from the entire length of the
blastoderm, and rapidly became compacted occupying approximately two-thirds of
the egg length. At about 7 h AEL, protocephalon and protocorm differentiation
occurred. Continued proliferation of the germ band was followed by penetration
into the yolk mass, forming a C-shaped embryo at about 10 h. Approximately 12 h
AEL, the gnathal, thoracic and abdominal segments became visible. The primordium
of the mouthparts and thoracic legs formed as paired evaginations, while the
prolegs formed as paired lobes. At about 30 h, the embryo reversed
dorsoventrally. Approximately 32 h AEL, the protocephalon and gnathal segments
fused, shifting the relative position of the rudimentary appendages in this
region. At about 52 h, the embryo was U-shaped in lateral view and at
approximately 56 h, the bristles began evagination from the larval cuticle.
Larvae hatched at about 72 h. We found that H. erato phyllis followed an
embryonic pattern consistent with long-germ embryogenesis. Thus, we believe that
H. erato phyllis should be classified as a long-germ lepidopteran. The study of
H. erato phyllis embryogenesis provided a structural glimpse into the
morphogenetic events that occur in the Heliconius egg period. This study could
help future molecular approaches to understanding the evolution of Heliconius
development.
PMID- 25112500
TI - Mobilization of patients on venovenous extracorporeal membrane oxygenation
support using an ECMO helmet.
PMID- 25112501
TI - The assessment of transpulmonary pressure in mechanically ventilated ARDS
patients.
AB - PURPOSE: The optimal method for estimating transpulmonary pressure (i.e. the
fraction of the airway pressure transmitted to the lung) has not yet been
established. METHODS: In this study on 44 patients with acute respiratory
distress syndrome (ARDS), we computed the end-inspiratory transpulmonary pressure
as the change in airway and esophageal pressure from end-inspiration to
atmospheric pressure (i.e. release derived) and as the product of the end
inspiratory airway pressure and the ratio of lung to respiratory system elastance
(i.e. elastance derived). The end-expiratory transpulmonary pressure was
estimated as the product of positive end-expiratory pressure (PEEP) minus the
direct measurement of esophageal pressure and by the release method. RESULTS: The
mean elastance- and release-derived transpulmonary pressure were 14.4 +/- 3.7 and
14.4 +/- 3.8 cmH2O at 5 cmH2O of PEEP and 21.8 +/- 5.1 and 21.8 +/- 4.9 cmH2O at
15 cmH2O of PEEP, respectively (P = 0.32, P = 0.98, respectively), indicating
that these parameters were significantly related (r(2) = 0.98, P < 0.001 at 5
cmH2O of PEEP; r(2) = 0.93, P < 0.001 at 15 cmH2O of PEEP). The percentage error
was 5.6 and 12.0 %, respectively. The mean directly measured and release-derived
transpulmonary pressure were -8.0 +/- 3.8 and 3.9 +/- 0.9 cmH2O at 5 cmH2O of
PEEP and -1.2 +/- 3.2 and 10.6 +/- 2.2 cmH2O at 15 cmH2O of PEEP, respectively,
indicating that these parameters were not related (r(2) = 0.07, P = 0.08 at 5
cmH2O of PEEP; r (2) = 0.10, P = 0.53 at 15 cmH2O of PEEP). CONCLUSIONS: Based on
our observations, elastance-derived transpulmonary pressure can be considered to
be an adequate surrogate of the release-derived transpulmonary pressure, while
the release-derived and directly measured end-expiratory transpulmonary pressure
are not related.
PMID- 25112502
TI - Myocardial viability in human septic heart.
PMID- 25112503
TI - Extracorporeal membrane oxygenation as a bridge to allogeneic T-cell depleted
hematopoietic stem cell transplantation in infants with severe combined immune
deficiency: is it feasible?
PMID- 25112505
TI - Assessment of arsenic availability in soils using the diffusive gradients in thin
films (DGT) technique--a comparison study of DGT and classic extraction methods.
AB - This study was conducted to evaluate the feasibility and accuracy of available
arsenic (As) measurement in soils using the diffusive gradients in thin films
(DGT) technique and to shed further light on the risk evaluation of As
contaminated soils. A bio-indicator method was used to evaluate the dependence of
As concentrations in plant tissues (edible rape) on the As concentrations
measured by other methods. DGT, extraction of soil pore water, 0.5 M NaHCO3, 1 M
HCl, 1 M NH4Cl, 0.5 M NH4F, 0.1 M NaOH and 0.25 M H2SO4 extraction methods, as
well as total As content in the soil were employed in this study. Edible rape was
grown in 43 soils containing different concentrations of As. A better correlation
was obtained between the As concentrations in plant tissues and the As
concentrations measured by DGT than between plant concentrations and those
measured by other methods. The coefficients of determination (R(2)) before and
after growth of edible rape were 0.84 and 0.83, respectively. Levels of As in
plants and in soil pore water were also closely related: the coefficients of
determination (R(2)) between these variables before and after growth of edible
rape were 0.83 and 0.81, respectively. Measurements from the chemical extraction
methods were inferior to those from DGT and soil pore water. Levels of As in
plants were more scattered and nonlinear with respect to total soil As content
(R(2) = 0.27). The As measured by DGT closely reflected the pool of plant
adsorbed As. From the data obtained in this study, we can conclude that DGT is an
effective technique for the prediction and assessment of As bioavailability in
soils.
PMID- 25112504
TI - Bacteriophage as effective decolonising agent for elimination of MRSA from
anterior nares of BALB/c mice.
AB - BACKGROUND: Nasal carriers not only pose serious threat to themselves but also to
the community by playing an active role in the dissemination of serious and life
threatening S. aureus especially MRSA strains. The present study focuses on the
use of broad spectrum lytic phage as decolonising agent. In addition, the
combined use of lytic phage with mupirocin has also been investigated as an
effective decolonising regimen. The effect of phage on the adherence, invasion
and cytotoxic effect of MRSA strains on nasal epithelial cells was studied in an
ex-vivo model of cultured murine nasal epithelial cells. This was followed by
demonstration of therapeutic potential of phage along with mupirocin in
decolonising the nares of BALB/c mice using a nasal model of MRSA colonisation.
RESULTS: Phage was able to significantly reduce the in vitro adherence, invasion
and cytotoxicity of MRSA 43300 as well as other clinical MRSA strains on murine
nasal epithelial cells as compared to untreated control. Also, the frequency of
emergence of spontaneous mutants decreased to negligible levels when both the
agents (phage and mupirocin) were used together. CONCLUSION: Phage MR-10, given
along with mupirocin showed an additive effect and the combination was able to
effectively eradicate the colonising MRSA population from the nares of mice by
day 5.
PMID- 25112506
TI - Photodynamic inactivation of bacterial and yeast biofilms with a cationic
porphyrin.
AB - The efficiency of 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetra
iodide (Tetra-Py(+)-Me) in the photodynamic inactivation of single-species
biofilms of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans
and mixed biofilms of S. aureus and C. albicans was evaluated. The effect on the
extracellular matrix of P. aeruginosa was also assessed. Irradiation with white
light up to an energy dose of 64.8 J cm(-2) in the presence of 20 MUm of Tetra
Py(+)-Me caused significant inactivation in all single-species biofilms (3-6 log
reductions), although the susceptibility was attenuated in relation to planktonic
cells. In mixed biofilms, the inactivation of S. aureus was as efficient as in
single-species biofilms but the susceptibility of C. albicans decreased. In P.
aeruginosa biofilms, a reduction of 81% in the polysaccharide content of the
matrix was observed after treatment with a 20 MUm PS concentration and a total
light dose of 64.8 J cm(-2). The results show that the Tetra-Py(+)-Me causes
significant inactivation of the microorganisms, either in biofilms or in the
planktonic form, and demonstrate that polysaccharides of the biofilm matrix may
be a primary target of photodynamic damage.
PMID- 25112507
TI - Motor neuron disease: Evaluation of ALS via transcranial magnetic stimulation.
PMID- 25112511
TI - Neuro-oncology: Under-recognized mental incapacity in brain tumour patients.
AB - Many patients with brain tumours possess inadequate mental capacity to provide
informed consent, but this situation often goes undetected because clinicians do
not routinely conduct formal cognitive assessments. This oversight should be
recognized and rectified to enable optimum ethical and medical care of these
vulnerable individuals.
PMID- 25112510
TI - Epilepsy: Beyond the single nucleotide variant in epilepsy genetics.
AB - Copy number variants (CNVs; deletions or duplications of chromosomal regions)
have emerged as an important cause of human disease. In a recent study, epilepsy
could be attributed to a pathogenic CNV in 5% of patients, but understanding the
implications of a CNV for an individual patient can be challenging.
PMID- 25112509
TI - The link between multiple sclerosis and depression.
AB - Depression--be it a formal diagnosis based on consensus clinical criteria, or a
collection of symptoms revealed by a self-report rating scale--is common in
patients with multiple sclerosis (MS) and adds substantially to the morbidity and
mortality associated with this disease. This Review discusses the prevalence and
epidemiology of depression in patients with MS, before covering aetiological
factors, including genetics, brain pathology, immunological changes,
dysregulation of the hypothalamic-pituitary-adrenal axis, and psychosocial
influences. Treatment options such as antidepressant drugs, cognitive-behavioural
therapy, mindfulness-based therapy, exercise and electroconvulsive therapy are
also reviewed in the context of MS-related depression. Frequent comorbid
conditions, namely pain, fatigue, anxiety, cognitive dysfunction and alcohol use,
are also summarized. The article then explores three key challenges facing
researchers and clinicians: what is the optimal way to define depression in the
context of diseases such as MS, in which the psychiatric and neurological
symptoms overlap; how can current knowledge about the biological and
psychological underpinnings of MS-related depression be used to boost the
validity of this construct; and can intervention be made more effective through
use of combination therapies with additive or synergistic effects, which might
exceed the modest benefits derived from their individual components?
PMID- 25112512
TI - Troponin elevations only detected with a high-sensitivity assay: clinical
correlations and prognostic significance.
AB - OBJECTIVES: With clinical use of high-sensitivity troponin I (hsTnI), more
frequent troponin elevations will occur. However, the burden and implications of
these elevations are not well understood. The authors quantified the prevalence
of elevated hsTnI in patients presenting with possible acute coronary syndrome
(ACS) who do not have elevated troponin with a current generation assay (cardiac
troponin I [cTnI]) and determined the association of these newly detected
elevations with a composite of all-cause mortality and subsequent cardiac
hospitalization. METHODS: This was a prospective observational study of 808
subjects evaluated for possible ACS and followed for up to 1 year. Troponin
values were measured with hsTnI (Abbott Laboratories) and cTnI (Abbott and
Beckman Coulter). Cardiac hospitalization was defined as hospitalization for ACS,
revascularization, acute heart failure (AHF), or tachy/brady arrhythmia that
occurred after the index emergency department (ED) visit or hospital discharge.
RESULTS: Forty subjects (5%) were diagnosed with ACS (26 myocardial infarction
and 14 unstable angina). On the initial sample, the prevalence of elevated hsTnI
among subjects with nonelevated cTnI was 9.2% using a gender-neutral cutoff (95%
confidence interval [CI] = 7.1% to 11.4%) and 11.1% using a gender-specific
cutoff (95% CI = 8.8% to 13.4%). Adjudicated diagnoses for subjects whose initial
samples had elevated hsTnI but nonelevated cTnI (gender-neutral cutoff) were as
follows: three (4.6%) ACS, 15 (23.1%) AHF, three (4.6%) volume overload etiology
unclear/noncardiac, three (4.6%) cardiac (non-ACS), and 41 (63.1%) other. Of the
65 patients whose initial samples had hsTnI but nonelevated cTnI, eight developed
cTnI elevation on subsequent serial sampling. After traditional cardiovascular
risk factors and renal function were adjusted for, subjects with elevated initial
hsTnI but nonelevated cTnI (initial and serial sampling) had a higher risk of all
cause mortality and subsequent cardiac hospitalization than subjects with both
nonelevated hsTnI and nonelevated cTnI (hazard ratio [HR] = 1.91, 95% CI = 1.14
to 3.19). CONCLUSIONS: On the initial sample, 9% to 11% of subjects without cTnI
elevation had hsTnI elevation. Although the majority of the patients with these
newly detected hsTnI elevations did not have ACS, they had a higher risk for all
cause mortality and subsequent cardiac hospitalization.
PMID- 25112508
TI - Treatment of neuromyelitis optica: state-of-the-art and emerging therapies.
AB - Neuromyelitis optica (NMO) is an autoimmune disease of the CNS that is
characterized by inflammatory demyelinating lesions in the spinal cord and optic
nerve, potentially leading to paralysis and blindness. NMO can usually be
distinguished from multiple sclerosis (MS) on the basis of seropositivity for IgG
antibodies against the astrocytic water channel aquaporin-4 (AQP4).
Differentiation from MS is crucial, because some MS treatments can exacerbate
NMO. NMO pathogenesis involves AQP4-IgG antibody binding to astrocytic AQP4,
which causes complement-dependent cytotoxicity and secondary inflammation with
granulocyte and macrophage infiltration, blood-brain barrier disruption and
oligodendrocyte injury. Current NMO treatments include general immunosuppressive
agents, B-cell depletion, and plasma exchange. Therapeutic strategies targeting
complement proteins, the IL-6 receptor, neutrophils, eosinophils and CD19--all
initially developed for other indications--are under clinical evaluation for
repurposing for NMO. Therapies in the preclinical phase include AQP4-blocking
antibodies and AQP4-IgG enzymatic inactivation. Additional, albeit currently
theoretical, treatment options include reduction of AQP4 expression, disruption
of AQP4 orthogonal arrays, enhancement of complement inhibitor expression,
restoration of the blood-brain barrier, and induction of immune tolerance.
Despite the many therapeutic options in NMO, no controlled clinical trials in
patients with this condition have been conducted to date.
PMID- 25112516
TI - Sponges associated with octocorals in the Indo-Pacific, with the description of
four new species.
AB - Sponges are characterised by high levels of phenotypic plasticity, thus allowing
the same species to live in different habitats by taking different shapes. Here
we describe 28 sponge species associated with the octocorals Carijoa riisei,
Paratelesto rosea and Alertigorgia hoeksemai in Indonesia, Hawai'i and Vietnam,
including four species that are new to science (Chondropsis subtilis, Hymedesmia
(Hymedesmia) spinata, Hymedesmia (Stylopus) perlucida, Mycale (Aegogropila)
furcata). Moreover, a large proportion of the described sponge species (21.4%)
represent new records for the studied areas (Indonesia and Hawai'i). In total, we
have studied 47 colonies of C. riisei associated with 24 sponge species, 5
colonies of P. rosea associated with 4 species and one colony of A. hoeksemai
associated with one sponge species. Collectively, these examples of associations
highlight the importance of epibiosis as a biodiversity enhancing process.
PMID- 25112517
TI - Highly enantioselective catalytic system for asymmetric copolymerization of
carbon dioxide and cyclohexene oxide.
AB - A new ligand can be easily prepared, and its intramolecular dinuclear zinc
complexes act as a high performance catalyst for the asymmetric alternating
copolymerization of cyclohexene oxide and CO2 under very mild conditions (1 atm
CO2 , room temperature), affording completely alternating polycarbonates with up
to 93.8 % enantiomeric excess (ee) and 98 % yield. A high Mn value of 28 600 and
a relatively narrow polydispersity (Mw /Mn ratio) of 1.43 were also achieved.
PMID- 25112515
TI - Admixture mapping identifies a quantitative trait locus associated with FEV1/FVC
in the COPDGene Study.
AB - African Americans are admixed with genetic contributions from European and
African ancestral populations. Admixture mapping leverages this information to
map genes influencing differential disease risk across populations. We performed
admixture and association mapping in 3,300 African American current or former
smokers from the COPDGene Study. We analyzed estimated local ancestry and SNP
genotype information to identify regions associated with FEV1 /FVC, the ratio of
forced expiratory volume in one second to forced vital capacity, measured by
spirometry performed after bronchodilator administration. Global African ancestry
inversely associated with FEV1 /FVC (P = 0.035). Genome-wide admixture analysis,
controlling for age, gender, body mass index, current smoking status, pack-years
smoked, and four principal components summarizing the genetic background of
African Americans in the COPDGene Study, identified a region on chromosome
12q14.1 associated with FEV1 /FVC (P = 2.1 * 10(-6) ) when regressed on local
ancestry. Allelic association in this region of chromosome 12 identified an
intronic variant in FAM19A2 (rs348644) as associated with FEV1 /FVC (P = 1.76 *
10(-6) ). By combining admixture and association mapping, a marker on chromosome
12q14.1 was identified as being associated with reduced FEV1 /FVC ratio among
African Americans in the COPDGene Study.
PMID- 25112518
TI - Design and characterization of a twin ribozyme for potential repair of a deletion
mutation within the oncogenic CTNNB1-DeltaS45 mRNA.
AB - RNA repair is an emerging strategy for gene therapy. Conventional gene therapy
typically relies on the addition of the corrected DNA sequence of a defective
gene to restore gene function. As an additional option, RNA repair allows
alteration of the sequence of endogenous messenger RNAs (mRNAs). mRNA sequence
alteration is either facilitated by intracellular spliceosome machinery or by the
intrinsic catalytic activity of trans-acting ribozymes. Previously we developed
twin ribozymes, derived from the hairpin ribozyme, by tandem duplication and
demonstrated their potential for patchwise RNA repair. Herein we describe the
development of such a twin ribozyme for potential repair of a deletion mutation
in the oncogenic CTNNB1-DeltaS45 mRNA. We demonstrate that hairpin ribozyme units
within the twin ribozyme can be adapted to efficiently cleave/ligate non
consensus substrates by introduction of compensatory mutations in the ribozyme.
Thus, we show the twin ribozyme mediated repair of truncated CTNNB1 transcripts
(up to 1000 nt length). Repair of the entire CTNNB1-DeltaS45 mRNA, although
apparently possible in general, is hampered in vitro by the secondary structure
of the transcript.
PMID- 25112514
TI - Selenium-enriched Spirulina protects INS-1E pancreatic beta cells from human
islet amyloid polypeptide-induced apoptosis through suppression of ROS-mediated
mitochondrial dysfunction and PI3/AKT pathway.
AB - PURPOSE: Human islet amyloid polypeptide (hIAPP) aggregation is linked to loss of
pancreatic beta cells in type 2 diabetes, in part due to oxidative stress.
Currently, little is known about the effects of selenium-enriched Spirulina on
beta cells with the presence of hIAPP. In this study, INS-1E rat insulinoma cells
were used as a model to evaluate in vitro protective effects of Se-enriched
Spirulina extract (Se-SE) against hIAPP-induced cell death, as well as the
underlying mechanisms. METHODS: Flow cytometric analysis was used to evaluate
cell apoptosis, mitochondrial membrane potential (DeltaPsim) and ROS generation.
Caspase activity was measured using a fluorometric method. Western blotting was
applied to detect protein expression. RESULTS: Our results showed that exposure
of INS-1E cells to hIAPP resulted in cell viability loss, LDH release and
appearance of sub-G peak. However, cytotoxicity of hIAPP was significantly
attenuated by co-treatment with Se-SE. Se-SE also inhibited hIAPP-induced
activation of caspase-3, -8 and -9. Additionally, hIAPP-induced accumulation of
ROS and superoxide was suppressed by co-treatment with Se-SE. Moreover, Se-SE was
able to prevent hIAPP-induced depletion of DeltaPsim and intracellular ATP,
reduction in mitochondrial mass, changes in the expression of Bcl-2 family
members, release of mitochondrial apoptogenic factors. Furthermore, hIAPP
mediated AKT inhibition was restored by co-treatment with Se-SE. CONCLUSION: Our
results showed that Se-SE protects INS-1E cells from hIAPP-induced cell death
through preventing ROS overproduction, mitochondrial dysfunction and modulating
PI3K/AKT pathway.
PMID- 25112519
TI - Sulfur(VI) fluoride exchange (SuFEx): another good reaction for click chemistry.
AB - Aryl sulfonyl chlorides (e.g. Ts-Cl) are beloved of organic chemists as the most
commonly used S(VI) electrophiles, and the parent sulfuryl chloride, O2 S(VI) Cl2
, has also been relied on to create sulfates and sulfamides. However, the desired
halide substitution event is often defeated by destruction of the sulfur
electrophile because the S(VI) ?Cl bond is exceedingly sensitive to reductive
collapse yielding S(IV) species and Cl(-) . Fortunately, the use of sulfur(VI)
fluorides (e.g., R-SO2 -F and SO2 F2 ) leaves only the substitution pathway open.
As with most of click chemistry, many essential features of sulfur(VI) fluoride
reactivity were discovered long ago in Germany.6a Surprisingly, this
extraordinary work faded from view rather abruptly in the mid-20th century. Here
we seek to revive it, along with John Hyatt's unnoticed 1979 full paper
exposition on CH2 ?CH-SO2 -F, the most perfect Michael acceptor ever found.98 To
this history we add several new observations, including that the otherwise very
stable gas SO2 F2 has excellent reactivity under the right circumstances. We also
show that proton or silicon centers can activate the exchange of S?F bonds for
S?O bonds to make functional products, and that the sulfate connector is
surprisingly stable toward hydrolysis. Applications of this controllable ligation
chemistry to small molecules, polymers, and biomolecules are discussed.
PMID- 25112520
TI - Generation and characterization of Lhx9-GFPCreER(T2) knock-in mouse line.
AB - LHX9 is a LIM-homeodomain transcription factor essential for the development of
gonads, spinal cord interneurons, and thalamic neurons to name a few. We recently
reported the expression of LHX9 in retinal amacrine cells during development. In
this study, we generated an Lhx9-GFPCreER(T) (2) (GCE) knock-in mouse line by
knocking-in a GCE cassette at the Lhx9 locus, thus inactivating endogenous Lhx9.
Lhx9(GCE) (/+) mice were viable, fertile, and displayed no overt phenotypical
characteristics. Lhx9(GCE) (/) (GCE) mice were all phenotypically female, smaller
in size, viable, but infertile. The specificity and efficacy of the Lhx9-GCE
mouse line was verified by crossing it to a Rosa26-tdTomato reporter mouse line,
which reveals the Cre recombinase activities in retinal amacrine cells,
developing limbs, testis, hippocampal neurons, thalamic neurons, and cerebellar
neurons. Taken together, the Lhx9-GCE mouse line could serve as a beneficial tool
for lineage tracing and gene manipulation experiments. genesis
PMID- 25112522
TI - Standards of practice for clinical pharmacists: the time has come.
PMID- 25112521
TI - The precuneus and visuospatial attention in near and far space: a transcranial
magnetic stimulation study.
AB - BACKGROUND: There is a large body of evidence for the involvement of the parietal
cortex in orientation and navigation in space. This has been supplemented by
investigation of the contribution of a number of subregions using transcranial
magnetic stimulation. OBJECTIVE: The role of the precuneus area, located in the
medial plane of posterior parietal cortex (PPC), in visuospatial functions is not
well understood. We investigated the contribution of this area using the landmark
task. METHODS: Participants were asked to make forced-choice judgments of which
side of prebisected line was longer for near and far viewing conditions (70 and
180 cm, respectively). Online 10 Hz, repetitive transcranial magnetic stimulation
(rTMS) was delivered for 500 ms over the right precuneus, rPPC and vertex
(control), in separate blocks of trials. The rPPC stimulation was used as a
positive control, having previously resulted in "neglect like" spatial bias
effects in a number of studies. RESULTS: A no-TMS condition showed a leftward
spatial bias (pseudoneglect) for near space judgments but not for far space and
was used as the baseline. Precuneus stimulation resulted in rightward spatial
bias from the midpoint in near space similar to the rPPC neglect-like effect. No
significant effects were seen with vertex stimulation. CONCLUSION: This study
shows that precuneus, like other parietal areas, is involved in visuospatial
functions. Further work is required to clarify how the contribution of this area
differs from other parietal regions.
PMID- 25112523
TI - Standards of practice for clinical pharmacists.
PMID- 25112524
TI - Does board certification really matter?
PMID- 25112525
TI - Clinical pharmacy should adopt a consistent process of direct patient care.
AB - Although the application of a consistent process of care serves as a foundational
principle for most health care professions, this is not true for the discipline
of clinical pharmacy. Without an explicit, reproducible process of care, it is
not possible to demonstrate to patients, caregivers, or health professionals the
ways in which the clinical pharmacist can reliably contribute to improved
medication-related outcomes. A consistent patient care process should describe
the key steps that all clinical pharmacists will follow when they encounter a
patient, regardless of the type of practice, the clinical setting, or the medical
conditions or medications involved. Four essential elements serve as the
cornerstones of the clinical pharmacist's patient care process: assess the
patient and his or her medication therapy, develop a plan of care, implement the
plan, and evaluate the outcomes of the plan. Despite the fact that several
processes of care have been advocated for clinical pharmacists, none has been
adopted by the clinical pharmacy discipline. In addition, numerous publications
evaluate outcomes related to clinical pharmacy services, but it is difficult to
determine what process of patient care was used in most of these studies. In our
view, a consistent process of direct patient care that includes the four
essential elements should be adopted by the clinical pharmacy discipline. This
process should be clear, straightforward and intuitive, readily documentable, and
applicable to all practice settings. Once adopted, the process should be
implemented across practice settings, taught in professional degree programs,
integrated into students' clinical rotations, refined during residency training,
and used as a foundation for future large-scale studies to rigorously study the
effects of the clinical pharmacist on patients' medication-related outcomes.
PMID- 25112526
TI - Successful use of octreotide as a chemoprotectant for prevention of PEG
asparaginase-induced pancreatitis.
AB - l-asparaginase is an aminohydrolase that deprives leukemia cells of l-asparagine
required for protein synthesis. Although studies in patients with acute
lymphoblastic leukemia have shown that the addition of l-asparaginase improved
the overall remission rate, life-threatening acute pancreatitis has occurred in
0.5-4% of patients. We describe the first adult case report, to our knowledge, of
the successful use of octreotide as a chemoprotectant for the prevention of
recurrent pegylated asparaginase (PEG-ASP)-induced pancreatitis in a 21-year-old
man with Philadelphia chromosome-negative acute lymphoblastic leukemia. After
recurrent PEG-ASP administration during induction chemotherapy, he developed
necrotizing pancreatitis, confirmed by abdominal computed tomography, and further
asparaginase therapy was withheld. Currently, there are no specific treatment
recommendations for the management of asparaginase-induced pancreatitis other
than drug discontinuation. After disease relapse, a pediatric PEG-ASP-containing
regimen was initiated, and PEG-ASP therapy was resumed due to its potential
clinical benefit. Octreotide 100 MUg subcutaneously 3 times/day, utilized as a
chemoprotectant, was found to prevent pancreatitis recurrence. The patient
completed therapy and was able to receive a bone marrow transplant without
further complications from PEG-ASP therapy. Based on this patient's experience,
we believe it is reasonable to reincorporate PEG-ASP after an episode of
pancreatitis with use of octreotide as a chemoprotectant; however, this
conclusion will need to be substantiated in a randomized clinical trial with a
larger group of patients.
PMID- 25112527
TI - Alternative viewpoint: preparation for residency.
PMID- 25112528
TI - Beta-blocker and antipsychotic treatment of toxicity from so-called designer
drugs.
PMID- 25112529
TI - Shaping of an effective immune microenvironment to and by cancer cells.
AB - A high density of intratumoral effector memory CD8+/Th1 T cells is associated
with favorable prognosis in most cancers and may be induced or increased by
immunotherapy. Efficient adaptive immune reactions are shaped in tumor adjacent
tertiary lymphoid structures, which exhibit all characteristics of immunity
generating lymphoid formations in reactive lymph nodes. Malignant tumor cells
impact favorably or deleteriously their immune microenvironment if they bear
genetic mutations that result in neo-antigens or by producing chemokines and
cytokines that recruit lymphocytes and myeloid cells or increase inflammation and
neo-angiogenesis. This intricate network of interactions results in control or
escape of tumors, and its understanding will help define goals to monitor
efficiency of immunotherapies.
PMID- 25112530
TI - Downregulation of microRNA-124 predicts poor prognosis in glioma patients.
AB - The aim of the present study was to investigate the clinical significance of
microRNA-124 (miR-124) expression in glioma. The expression levels of miR-124
were measured using quantitative real-time polymerase chain reaction (qRT-PCR)
analysis. The correlation between the miR-124 levels and the clinicopathological
factors of the glioma patients was analyzed. The survival curves were calculated
by the Kaplan-Meier method. The influence of each variable on survival was
examined by the Cox multivariate regression analysis. Compared with nonneoplastic
brain tissues, the expression level of miR-124 was significantly decreased in
glioma tissues (1.27 +/- 0.55 versus 6.91 +/- 1.06, P < 0.0001). The expression
level of miR-124 was positively correlated with grade (P = 0.003) and Karnofsky
performance status (KPS) score (P = 0.008). A significant difference was found
that glioma patients with low miR-124 expression level had distinctly shorter OS
(P = 0.001) and PFS (P = 0.002) than patients with high miR-124 expression level.
Furthermore, we found that low miR-124 expression (OS P = 0.009; PFS P = 0.002)
and advanced histologic grade (OS P = 0.005; PFS P = 0.001) were independent
prognostic parameters indicating poor prognosis for glioma patients. Our results
showed that the decreased expression of miR-124 may be associated with malignant
tumor progression and poor prognosis in patients with gliomas, suggesting that
miR-124 may be a novel and valuable signature for predicting the clinical outcome
of patients with gliomas.
PMID- 25112531
TI - Role of physical activity in reducing cognitive decline in older Mexican-American
adults.
AB - The effect of physical activity on cognitive function in older adults from
minority and disadvantaged populations is not well understood. This study
examined the longitudinal association between physical activity and cognition in
older Mexican Americans. The study methodology included a prospective cohort with
longitudinal analysis of data from the Hispanic Established Populations for the
Epidemiologic Study of the Elderly. General linear mixed models were used to
assess the associations and interactions between physical activity and cognitive
function over 14 years. Community-based assessments were performed in
participants' homes. Physical activity was recorded for 1,669 older Mexican
Americans using the Physical Activity Scale for the Elderly. Cognition was
measured using the Mini-Mental State Examination (MMSE) and separated into memory
and nonmemory components. A statistically significant positive association was
observed between levels of physical activity and cognitive function after
adjusting for age, sex, marital status, education, and comorbid health
conditions. There was a statistically significant difference in MMSE scores over
time between participants in the third (beta = 0.11, standard error (SE) = 0.05)
and fourth (beta = 0.10, SE = 0.2) quartiles of physical activity and those in
the first. The protective effect of physical activity on cognitive decline was
evident for the memory component of the MMSE but not the nonmemory component
after adjusting for covariates. Greater physical activity at baseline was
associated with less cognitive decline over 14 years in older Mexican Americans.
The reduction in cognitive decline appeared to be related to the memory
components of cognitive function.
PMID- 25112532
TI - Modern extraction techniques and their impact on the pharmacological profile of
Serenoa repens extracts for the treatment of lower urinary tract symptoms.
AB - BACKGROUND: Bioactive compounds from plants (i.e., Serenoa repens) are often used
in medicine in the treatment of several pathologies, among which benign prostatic
hyperplasia (BPH) associated to lower urinary tract symptoms (LUTS). DISCUSSION:
There are different techniques of extraction, also used in combination, with the
aim of enhancing the amount of the target molecules, gaining time and reducing
waste of solvents. However, the qualitative and quantitative composition of the
bioactives depends on the extractive process, and so the brands of the recovered
products from the same plant are different in terms of clinical efficacy (no
product interchangeability among different commercial brands). SUMMARY: In this
review, we report on several and recent extraction techniques and their impact on
the composition/biological activity of S. repens-based available products.
PMID- 25112533
TI - A multi-institution evaluation of MLC log files and performance in IMRT delivery.
AB - BACKGROUND: The multileaf collimator (MLC) is a critical component to accurate
intensity-modulated radiotherapy (IMRT) delivery. This study examined MLC
positional accuracy via MLC logs from Varian machines from six institutions and
three delivery techniques to evaluate typical positional accuracy and treatment
and mechanical parameters that affect accuracy. Typical accuracy achieved was
compared against TG-142 recommendations for MLC performance; more appropriate
recommendations are suggested. METHODS: Over 85,000 Varian MLC treatment logs
were collected from six institutions and analyzed with FractionCHECK. Data were
binned according to institution and treatment type to determine overall root mean
square (RMS) and 95th percentile error values, and then to look for correlations
between those errors and with mechanical and treatment parameters including mean
and maximum leaf speed, gantry angle, beam-on time, mean leaf error, and number
of segments. RESULTS: Results of treatment logs found that leaf RMS error and
95th percentile leaf error were consistent between institutions, but varied by
treatment type. The step and shoot technique had very small errors: the mean RMS
leaf error was 0.008 mm. For dynamic treatments the mean RMS leaf error was 0.32
mm, while volumetric-modulated arc treatment (VMAT) showed an RMS leaf error of
0.46 mm. Most MLC leaf errors were found to be well below TG-142 recommended
tolerances. For the dynamic and VMAT techniques, the mean and maximum leaf speeds
were significantly linked to the leaf RMS error. Additionally, for dynamic
delivery, the mean leaf error was correlated with RMS error, whereas for VMAT the
average gantry speed was correlated. For all treatments, the RMS error and the
95th percentile leaf error were correlated. CONCLUSIONS: Restricting the maximum
leaf speed can help improve MLC performance for dynamic and VMAT deliveries.
Furthermore, the tolerances of leaf RMS and error counts for all treatment types
should be tightened from the TG-142 values to make them more appropriate for
clinical performance. Values of 1 mm for the 95th percentile of leaf RMS error
and 1.5 mm for the 95th percentile leaf error are suggested as action levels for
all treatment types.
PMID- 25112534
TI - Direct comparison of the different conventional laparoscopic positions with the
ethos surgical platform in a laparoscopic pelvic surgery simulation setting.
AB - OBJECTIVE: Laparoscopic surgery can be harmful to surgeons requiring a prolonged
learning curve due to significant ergonomic drawbacks. Based on preliminary
clinical experience, we present an experimental evaluation of the second
generation ETHOSTM operating chair by comparing it with two different operating
positions of conventional laparoscopic pelvic surgery. MATERIALS AND METHODS: The
ETHOS operation platform consists of a seat like a saddle and five more parts
that can be adjusted individually to support the surgeon's trunk and extremities.
This operation platform was tested in 30 trainees who performed three standard
suturing exercises in a pelvitrainer, approximating a linear and a U-shaped
incision, made on the skin of a chicken leg, and completing an urethrovesical
anastomosis, on a pig bladder specimen model, using interrupted sutures. The
trainees performed each exercise in standing laterally to pelvitrainer (torero
position) vs standing behind pelvi-trainer and sitting on ETHOS. The mean values,
from all times and for each exercise and position, were documented, and the
participants filled out a validated questionnaire focusing on ergonomic issues.
RESULTS: There were no significant differences among the different training
modalities, in step 1 and step 2. However, in step 3, which mimics the
urethrovesical anastomosis, the mean times were statistically significant
significantly less by using ETHOS (p<0.0001). The mean times of training in step
3 were 41.2 minutes in the behind the camera position, 49 minutes in torero
position, and 39.7 minutes by using ETHOS. The position that was maintained,
during the exercises, was mainly responsible for the improvement noted in the
ergonomic scores. CONCLUSIONS: The new operating platform (ETHOS chair) can
significantly improve ergonomics in laparoscopy particularly concerning difficult
steps like intracorporeal suturing. This may also improve the urethrovesical
anastomosis times in a clinical setting.
PMID- 25112536
TI - Survey of Victorian ophthalmologists who use ranibizumab to treat age-related
macular degeneration: to identify current practice and modifiable risk factors
relevant to post-injection endophthalmitis.
PMID- 25112535
TI - Now you see it, now you don't: Testing environments modulate the association
between hippocampal volume and cortisol levels in young and older adults.
AB - The hypothalamic pituitary adrenal axis production of the stress hormone cortisol
interacts with the hippocampal formation and impacts memory function. A growing
interest is to determine whether hippocampal volume (HV) predicts basal and/or
reactive cortisol levels in young and older adults. Recent evidence shows that
contextual features in testing environments might be stressful and inadvertently
induce a stress response in young and/or older populations. This latter result
suggests that variations in testing environments might influence associations
between HV and cortisol levels in young and older adults. To this end, we
investigated 28 healthy young adults (ages 18-35) and 32 healthy older adults
(ages 60-75) in two different environments constructed to be more or less
stressful for each age group (Favoring-Young versus Favoring-Old conditions).
Cortisol levels were repeatedly assessed in each environment, and young and older
participants underwent an anatomical magnetic resonance imaging scan for
subsequent assessment of HV. Results in both age groups showed that HV was
significantly associated with cortisol levels only in the unfavorable stressful
testing conditions specific for each age group. This association was absent when
testing environments were designed to decrease stress for each age group. These
findings are fundamental in showing that unless the nature of the testing
environment is taken into consideration, detected associations between HV and
cortisol levels in both young and older populations might be confounded by
environmental stress.
PMID- 25112537
TI - Nanocomplexes based on amphiphilic hyaluronic acid derivative and polyethylene
glycol-lipid for ginsenoside rg3 delivery.
AB - Hybrid nanocomplex formulations, based on amphiphilic hyaluronic acid-ceramide
(HACE) and lipids, were fabricated for the delivery of 20(S)-ginsenoside Rg 3
[(S)-Rg3]. Nanocomplexes with less than 200 nm mean diameter, narrow size
distribution, spherical shape, and negative zeta potential were prepared. The
maintenance of the structural stability of the hybrid nanocomplexes in the blood
stream was demonstrated by measuring their particle size in serum. Nanocomplexes
based on HACE, phosphatidylcholine (PC), and 1,2-distearoyl-sn-glycero-3
phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-PEG) showed a
sustained drug release profile compared with other formulations. Blank
nanocomplexes exhibited negligible cytotoxicity within the tested concentration
range in A549 human lung adenocarcinoma cells. The cellular uptake efficiency of
hybrid nanocomplexes was improved compared with the HACE-based nanoparticles
probably because of interactions between lipids and the cellular membrane. The
results of a pharmacokinetic study in rats revealed decreased in vivo clearance
of (S)-Rg3, especially in the HACE/PC/DSPE-PEG-based hybrid nanocomplex (F3)
group. The hybrid nanostructure and the outer PEG chain likely contributed to
improve in vivo performance of the F3 group. Thus, these developed hybrid
nanocomplexes could serve as good candidates for tumor-targeted delivery of
anticancer agents.
PMID- 25112538
TI - Hyperuricemia and chronic kidney disease: an enigma yet to be solved.
AB - The role of uric acid (UA) on the pathogenesis and progression of chronic kidney
disease (CKD) remains controversial. Experimental and clinical studies indicate
that UA is associated with several risk factors of CKD including diabetes,
hypertension, oxidative stress, and inflammation and hyperuricemia could be
considered as a common dominator linking CKD and cardiovascular disease. Notably,
the impact of serum UA levels on the survival of CKD, dialysis patients, and
renal transplant recipients is also a matter of debate, as there are conflicting
results from clinical studies. At present, there is no definite data whether UA
is causal, compensatory, coincidental or it is only an epiphenomenon in these
patients. In this article, we attempt to review and elucidate the dark side of
this old molecule in CKD and renal transplantation.
PMID- 25112539
TI - Metal artefact reduction algorithms prevent false positive results when assessing
patients for cardiac implantable electronic device infection.
AB - Software-based metal artefact reduction (MAR) techniques are available to reduce
artefacts from cardiac implantable electronic devices (CIED) in the CT data. The
impact of disabling MAR techniques on quantification of 18F-FDG uptake around the
CIED has not been examined. We consider the importance of enabling MAR in
patients with suspected CIED infection to prevent inaccuracies in quantification
of tissue tracer uptake on the attenuation-corrected PET images.
PMID- 25112540
TI - The potential role of gated myocardial perfusion SPECT imaging in patient
selection for cardiac resynchronization therapy.
PMID- 25112541
TI - Evaluation of the breeding soundness of male camels (Camelus dromedarius) via
clinical examination, semen analysis, ultrasonography and testicular biopsy: a
summary of 80 clinical cases.
AB - Male camel infertility is a heterogeneous disorder. A variety of factors may
adversely affect sperm production and function and impair fertility. This study
was designed to evaluate the sensitivity and specificity of ultrasonography and
testicular biopsy in the evaluation of the breeding soundness of male dromedaries
compared with results obtained by clinical examination and semen analysis. Eighty
four male dromedary camels (5-15 years old) were used in this study during the
rutting season (November-May). Four sexually mature male camels were used as
controls. These animals were apparently healthy and had histories of normal
fertility. Eighty infertile male camels were subjected to an algorithmic approach
based on information collected during careful examinations of the camels'
breeding histories, clinical examinations, testicular evaluations, testicular
ultrasonographies, the results of the semen analyses and testicular biopsies to
diagnose the camels' infertilities. The differences in the semen parameters
between the control and infertile male camels were highly significant (p < 0.01).
Regarding the diagnoses of male camel infertility, the results of testicular
ultrasonographies and biopsies were compared with those from the semen analyses,
and the accuracies of these tests were 92.5% and 90%, respectively. Additionally,
the results of the testicular ultrasonographies were matched with those of the
testicular biopsies of the infertile animals, and this comparison resulted in 85%
accuracy. Testicular biopsy is a promising method that, along with a carefully
performed history, clinical examination, an appropriate testicular
ultrasonography procedure and semen analysis, can afford veterinarians the
opportunity for more precise diagnosis and treatment of many dromedary
infertility disorders.
PMID- 25112543
TI - Ophthalmoplegia in congenital neuromuscular disease with uniform type 1 fiber.
AB - Congenital neuromuscular disease with uniform type 1 fiber (CNMDU1) is a rare
type of congenital myopathy. It is characterized by early onset of symptoms, mild
proximal muscle weakness, hyporeflexia or areflexia, normal serum creatine kinase
(CK) levels and myopathic electromyography finding, uniform type 1 fibers, and
nonprogression. We report a 2-year-old boy who presented with congenital
hypotonia, breathing and feeding difficulty, myopathic facies, proximal muscle
weakness, ptosis, total external ophthalmoplegia and delayed motor developmental
milestones. Normal serum muscle enzyme and short duration of motor unit
potentials on electromyography were noted. Muscle biopsy showed uniformity of
type 1 fibers (greater than 99%) and moderate variation in fiber size without
specific structural abnormality. Total external ophthalmoplegia may be one of the
important clinical manifestations of CNMDU1. It is important to recognize this
disorder because it is nonprogressive in nature.
PMID- 25112542
TI - Pharmacological management of central post-stroke pain: a practical guide.
AB - Pain is one of the most troublesome sequelae of stroke. Some of this post-stroke
pain is caused by the brain lesion itself; this is called central post-stroke
pain (CPSP). Although the prevalence of CPSP is low (1-8 %), persistent, often
treatment-resistant, painful sensations are a major problem for stroke patients.
The pathogenesis of CPSP remains unknown, but suggested underlying causes include
hyperexcitation in the damaged sensory pathways, damage to the central inhibitory
pathways, or a combination of the two. For pharmacological treatment,
amitriptyline, an adrenergic antidepressant, is currently the first-line drug for
CPSP. However, its effect is frequently incomplete and a high dose is commonly
not tolerated in stroke patients. Lamotrigine, an antiepileptic, was also found
to be effective in a controlled trial and can be used as an alternative or
additive therapy. GABAergic drugs with potential calcium channel-blocking
effects, such as gabapentin or pregabalin, have recently emerged as a potentially
useful therapy. These drugs are effective in various neuropathic pain syndromes,
but their effect on CPSP remains to be proven. Pregabalin may improve pain
related anxiety and sleep disturbances. Fluvoxamine and mexiletine may be used
adjunctively in some patients. Non-pharmacological treatments such as motor
cortex stimulation or deep brain stimulation are used in some centers, but are
not proven to be effective. Further well designed clinical trials as well as
basic research should be performed to improve our understanding of the
pathophysiology of CPSP and to develop better treatment strategies.
PMID- 25112544
TI - A resting state functional magnetic resonance imaging study of concussion in
collegiate athletes.
AB - Sports-related concussions are currently diagnosed through multi-domain
assessment by a medical professional and may utilize neurocognitive testing as an
aid. However, these tests have only been able to detect differences in the days
to week post-concussion. Here, we investigate a measure of brain function, namely
resting state functional connectivity, which may detect residual brain
differences in the weeks to months after concussion. Twenty-one student athletes
(9 concussed within 6 months of enrollment; 12 non-concussed; between ages 18 and
22 years) were recruited for this study. All participants completed the Wisconsin
Card Sorting Task and the Color-Word Interference Test. Neuroimaging data,
specifically resting state functional Magnetic Resonance Imaging data, were
acquired to examine resting state functional connectivity. Two sample t-tests
were used to compare the neurocognitive scores and resting state functional
connectivity patterns among concussed and non-concussed participants.
Correlations between neurocognitive scores and resting state functional
connectivity measures were also determined across all subjects. There were no
significant differences in neurocognitive performance between concussed and non
concussed groups. Concussed subjects had significantly increased connections
between areas of the brain that underlie executive function. Across all subjects,
better neurocognitive performance corresponded to stronger brain connectivity.
Even at rest, brains of concussed athletes may have to 'work harder' than their
healthy peers to achieve similar neurocognitive results. Resting state brain
connectivity may be able to detect prolonged brain differences in concussed
athletes in a more quantitative manner than neurocognitive test scores.
PMID- 25112545
TI - Filter wire fracture during transradial carotid stenting.
PMID- 25112546
TI - Poor response to antidepressants predicts new suicidal ideas and behavior in
depressed outpatients.
AB - BACKGROUND: Only a few studies have investigated the factors associated with
suicidal behavior after antidepressant treatment onset in adults. We examined the
specific predictors of de novo suicidal ideas or attempts among depressed
patients in the community, including subjects potentially at risk of suicidal
behaviors, who initiated a new antidepressant treatment. METHODS: A large set of
GPs and psychiatrists throughout France followed-up, for 6 weeks, 4357
outpatients for whom an antidepressant drug was prescribed. Dimensions related
with antidepressant-induced suicidal events, such as depression, anxiety or
hopelessness, were assessed longitudinally using univariate and multivariate
approaches among subjects with treatment-emergent suicide ideation or attempts.
RESULTS: New suicidal ideas were observed in 9% of patients with no suicidal
ideation at baseline (n=81), while suicidal attempts were reported for 1.7% of
the sample during the 6-week observation period (n=75). The onset of suicidal
ideas and attempts was associated with the initial features of the patients
(baseline level of anxiety, past history of suicide attempts and alcohol misuse)
and the non-improvement of depression. Worsening of depressive symptoms during
the follow-up increased the onset of new suicidal ideas (OR=5.67, p<0.001) and
attempts (OR=2.60, p=0.002), corresponding to 67.5% and 56.5% of attributable
risk respectively. CONCLUSIONS: When the analyses are restricted to the
occurrence of suicidal ideas or attempts, the link between antidepressants and
suicide risk might be more adequately explained by a poor response to
antidepressant treatment rather than by a direct trigger-effect. This
naturalistic study is limited by the use of non-structured diagnoses and self
report outcomes.
PMID- 25112547
TI - [Prevalence of sleep disorders and associated factors in inpatient].
AB - OBJECTIVE: To determine the prevalence of insomnia in inpatient in an Internal
Medicine Department and to identify risk factors of sleep disorders. METHOD: A
cross-sectional observational study was designed. Inpatients over eighteen years
old hospitalized for acute medical conditions were recruited. Insomnia was
assessed by the Athens insomnia scale. A nurse administered a questionnaire on
risk factors including socio-demographic factors, reason for admission,
comorbidities, current medications, functional status, nocturnal symptoms, and
environmental factors. RESULTS: A total of 299 patients were recruited with a
mean age of 73.7 years (SD 14.2). Overall prevalence of insomnia was 42.1%,
slightly higher in women (48.2%) than in men (37.0%) (P=.052). In those less than
65 years the prevalence was 33.8%, and in patients aged 65 or over it was 44.9%
(P=.093). The main factors associated with insomnia were a history of anxiety,
depression and stroke, heartburn, pain, fear, and poor functional capacity at
admission. Environmental factors such as noise, the sensation of cold or heat,
and changing habits involved in hospitalization did not reach statistical
significance. In patients 65 years or older, the use of beta-blockers was
associated with insomnia. The multivariate analysis showed stroke, heartburn, and
pain as independent risk factors for insomnia. CONCLUSIONS: Insomnia is highly
prevalent among inpatient, and is associated with some treatable or modifiable
factors.
PMID- 25112548
TI - The detection of neural autoantibodies in patients with antiepileptic-drug
resistant epilepsy predicts response to immunotherapy.
AB - BACKGROUND AND PURPOSE: The detection of antibodies binding neural antigens in
patients with epilepsy has led to the definition of 'autoimmune epilepsy'.
Patients with neural antibodies not responding to antiepileptic drugs (AEDs) may
benefit from immunotherapy. Aim of this study was to evaluate the frequency of
autoantibodies specific to neural antigens in patients with epilepsy and their
response to immunotherapy. METHODS: Eighty-one patients and 75 age- and sex
matched healthy subjects (HS) were enrolled in the study. Two groups of patients
were included: 39 patients with epilepsy and other neurological symptoms and/or
autoimmune diseases responsive to AEDs (group 1) and 42 patients with AED
resistant epilepsy (group 2). Patients' serum and cerebrospinal fluid were
evaluated for the presence of autoantibodies directed to neural antigens by
indirect immunofluorescence on frozen sections of mouse brain, cell-based assays
and a radioimmunoassay. Patients with AED-resistant epilepsy and neural
autoantibodies were treated with immunotherapy and the main outcome measure was
the reduction in seizure frequency. RESULTS: Neural autoantibodies were detected
in 22% of patients (18/81), mostly from the AED-resistant epilepsy group (P =
0.003), but not in HS. Indirect immunofluorescence on mouse brain revealed
antibodies binding to unclassified antigens in 10 patients. Twelve patients
received immunotherapy and nine (75%) achieved >50% reduction in seizure
frequency. CONCLUSIONS: A significant proportion of patients with AED-resistant
epilepsy harbor neural-specific autoantibodies. The detection of these
antibodies, especially of those binding to synaptic antigens, may predict a
favorable response to immunotherapy, thus overcoming AED resistance.
PMID- 25112549
TI - Minocycline protects against oxidative damage and alters energy metabolism
parameters in the brain of rats subjected to chronic mild stress.
AB - Studies have been suggested that minocycline can be a potential new agent for the
treatment of depression. In addition, both oxidative stress and energy metabolism
present an important role in pathophysiology of depression. So, the present study
was aimed to evaluate the effects of minocycline on stress oxidative parameters
and energy metabolism in the brain of adult rats submitted to the chronic mild
stress protocol (CMS). After CMS Wistar, both stressed animals as controls
received twice ICV injection of minocycline (160 MUg) or vehicle. The oxidative
stress and energy metabolism parameters were assessed in the prefrontal cortex
(PF), hippocampus (HIP), amygdala (AMY) and nucleus accumbens (Nac). Our findings
showed that stress induced an increase on protein carbonyl in the PF, AMY and
NAc, and mynocicline injection reversed this alteration. The TBARS was increased
by stress in the PF, HIP and NAc, however, minocycline reversed the alteration in
the PF and HIP. The Complex I was incrased in AMY by stress, and minocycline
reversed this effect, however reduced Complex I activity in the NAc; Complex II
reduced in PF and AMY by stress or minocycline; the Complex II-III increased in
the HIP in stress plus minocycline treatment and in the NAc with minocycline; in
the PF and HIP there were a reduced in Complex IV with stress and minocycline.
The creatine kinase was reduced in AMY and NAc with stress and minocycline. In
conclusion, minocycline presented neuroprotector effects by reducing oxidative
damage and regulating energy metabolism in specific brain areas.
PMID- 25112551
TI - N-nitrosodimethylamine (NDMA) formation potential of amine-based water treatment
polymers: Effects of in situ chloramination, breakpoint chlorination, and pre
oxidation.
AB - Recent studies show that cationic amine-based water treatment polymers may be
important precursors that contribute to formation of the probable human
carcinogen N-nitrosodimethylamine (NDMA) during water treatment and disinfection.
To better understand how water treatment parameters affect NDMA formation from
the polymers, the effects of in situ chloramination, breakpoint chlorination, and
pre-oxidation on the NDMA formation from the polymers were investigated. NDMA
formation potential (NDMA-FP) as well as dimethylamine (DMA) residual
concentration were measured from poly(epichlorohydrin dimethylamine) (polyamine)
and poly(diallyldimethylammonium chloride) (polyDADMAC) solutions upon reactions
with oxidants including free chlorine, chlorine dioxide, ozone, and
monochloramine under different treatment conditions. The results supported that
dichloramine (NHCl2) formation was the critical factor affecting NDMA formation
from the polymers during in situ chloramination. The highest NDMA formation from
the polymers occurred near the breakpoint of chlorination. Polymer chain
breakdown and transformation of the released DMA and other intermediates were
important factors affecting NDMA formation from the polymers in pre-oxidation
followed by post-chloramination. Pre-oxidation generally reduced NDMA-FP of the
polymers; however, the treatments involving pre-ozonation increased polyDADMAC's
NDMA-FP and DMA release. The strategies for reducing NDMA formation from the
polymers may include the avoidance of the conditions favorable to NHCl2 formation
and the avoidance of polymer exposure to strong oxidants such as ozone.
PMID- 25112550
TI - Competitive antagonism of insect GABA receptors by 4-substituted 5-(4-piperidyl)
3-isothiazolols.
AB - gamma-Aminobutyric acid (GABA) receptors are important targets of
parasiticides/insecticides. Several 4-substituted analogs of the partial GABAA
receptor agonist 5-(4-piperidyl)-3-isothiazolol (Thio-4-PIOL) were synthesized
and examined for their antagonism of insect GABA receptors expressed in
Drosophila S2 cells or Xenopus oocytes. Thio-4-PIOL showed weak antagonism of
three insect GABA receptors. The antagonistic activity of Thio-4-PIOL was
enhanced by introducing bicyclic aromatic substituents into the 4-position of the
isothiazole ring. The 2-naphthyl and the 3-biphenylyl analogs displayed
antagonist potencies with half maximal inhibitory concentrations in the low
micromolar range. The 2-naphthyl analog induced a parallel rightward shift of the
GABA concentration-response curve, suggesting competitive antagonism by these
analogs. Both compounds exhibited weak insecticidal activities against
houseflies. Thus, the orthosteric site of insect GABA receptors might be a
potential target site of insecticides.
PMID- 25112552
TI - Investigation of potential soil contamination with Cr and Ni in four metal
finishing facilities at Asopos industrial area.
AB - The objective of this work was to investigate whether previous disposal practices
in four metal finishing facilities, located at Asopos river basin (East-Central
Greece), have caused any potential serious contamination of soils. The study
focused mainly on Cr and Ni, which are the primary elements of concern in the
area. To estimate the natural geochemical levels of Cr and Ni, thirty soil
samples were collected from locations that were not suspected of any
contamination. In this group of samples, Cr concentration varied between 60 and
418 mg/kg, and Ni concentrations varied from 91 to 1200 mg/kg. The second group
of samples consisted of more than 100 drill cores and surface soil samples,
potentially affected by the disposal of effluents and/or the drainage of runoff
water from the industrial facilities. According to the findings of the study, the
disposal of treated effluents in absorption type sinks resulted occasionally in
the contamination of a thin layer of soil just at the bottom of the sinks, but
there was no indication of downward migration, since Cr and Ni concentrations in
the lower soil layers were similar to those of the reference soils.
PMID- 25112554
TI - Physical activity below the minimum international recommendations improves
oxidative stress, ADMA levels, resting heart rate and small artery endothelial
function.
AB - BACKGROUND: A moderate level of physical activity (PA), such as a daily 30-min
walk, reduces cardiovascular risk. There is a lack of evidence about the
cardiovascular benefits of PA below this recommendation of minimum PA level.
OBJECTIVE: We aimed to study the impact of a lower level of PA on cardiovascular
health. DESIGN: Sixty-four overweight/obese men and women were enrolled in a
community programme consisting of 4 months of 1h, low-intensity PA two days per
week. Before and after the intervention, PA level (METs/h/wk), endogenous
antioxidant status (SOD and GPX concentration and activity and oxidised LDL),
ADMA concentrations, endothelial function by small artery reactive hyperaemia
index (saRHI), and resting heart rate (RHR) were assessed. RESULTS: After the
intervention, significant increases in saRHI (P=0.031), SOD and GPX activities,
and a decrease in ADMA plasma concentrations, and RHR (P<0.001 for all) were
observed. Increases in PA were positively associated with increases in saRHI
(r=0.341, P=0.022), GPx (r=0.303, P=0.047) and decreases in RHR (r=-0.302,
P=0.047). Multivariate analyses showed that independent predictors of saRHI
improvement were an increase in PA (2.65, 95%CI: 1.21-4.01), decrease in RHR
(1.91, 95%CI: 1.01-4.98), and an increase in GPx (2.61, 95%CI: 1.16-5.01).
CONCLUSION: In obese and overweight men and women, an increase in PA, even below
the minimal international recommendations, improves antioxidant capacity, RHR and
peripheral small artery reactivity.
PMID- 25112555
TI - Trends in the incidence and management of acute myocardial infarction from 1999
to 2008: get with the guidelines performance measures in Taiwan.
AB - BACKGROUND: The American Heart Association Get With the Guidelines (GWTG) program
has improved care quality of acute myocardial infarction (AMI) with important
implications for other countries in the world. This study evaluated the incidence
and care of AMI in Taiwan and assessed the compliance of GWTG in Taiwan. METHODS
AND RESULTS: We used the Taiwan National Health Insurance Research Database (1999
2008) to identify hospitalized patients >=18 years of age presenting with AMI.
The temporal trends of annual incidence and care quality of AMI were evaluated.
The age-adjusted incidence of AMI (/100 000 person-years) increased from 28.0 in
1999 to 44.4 in 2008 (P<0.001). The use of guideline-based medications for AMI
was evaluated. The use of dual antiplatelet therapy (DAPT) increased from 65% in
2004 to 83.9% in 2008 (P<0.001). Angiotensin-converting enzyme (ACE) inhibitor or
angiotensin receptor blocker (ARB) was used in 72.6% in 2004 and 71.7% in 2008
(P=NS) and beta-blocker was used in 60% in 2004 and 59.7% in 2008 (P=NS). Statin
use increased from 32.1% to 50.1% from 2004 to 2008 (P<0.001). The in-hospital
mortality decreased from 15.9% in 1999 to 12.3% in 2008 (P<0.0001). Multivariable
analysis showed that DAPT, ACE inhibitor/ARB, beta-blocker, and statin use during
hospitalization were all associated with reduced in-hospital mortality in our AMI
patients. CONCLUSIONS: AMI incidence was increasing, but the guideline-based
medications for AMI were underutilized in Taiwan. Quality improvement programs,
such as GWTG, should be promoted to improve AMI care and outcomes in Taiwan.
PMID- 25112556
TI - Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification and vascular
territory of ischemic stroke lesions diagnosed by diffusion-weighted imaging.
AB - BACKGROUND: The association between the location and the mechanism of a stroke
lesion remains unclear. A diffusion-weighted imaging study may help resolve this
lack of clarity. METHODS AND RESULTS: We studied a consecutive series of 2702
acute ischemic stroke patients whose stroke lesions were confirmed by diffusion
weighted imaging and who underwent a thorough etiological investigation. The
vascular territory in which an ischemic lesion was situated was identified using
standard anatomic maps of the dominant arterial territories. Stroke subtype was
based on the Trial of ORG 10172 in Acute Stroke Treatment, or TOAST,
classification. Large-artery atherosclerosis (37.3%) was the most common stroke
subtype, and middle cerebral artery (49.6%) was the most frequently involved
territory. Large-artery atherosclerosis was the most common subtype for anterior
cerebral, middle cerebral, vertebral, and anterior and posterior inferior
cerebellar artery territory infarctions. Small vessel occlusion was the leading
subtype in basilar and posterior cerebral artery territories. Cardioembolism was
the leading cause in superior cerebellar artery territory. Compared with carotid
territory stroke, vertebrobasilar territory stroke was more likely to be caused
by small vessel occlusion (21.4% versus 30.1%, P<0.001) and less likely to be
caused by cardioembolism (23.2% versus 13.8%, P<0.001). Multiple-vascular
territory infarction was frequently caused by cardioembolism (44.2%) in carotid
territory and by large-artery atherosclerosis (52.1%) in vertebrobasilar
territory. CONCLUSIONS: Information on vascular territory of a stroke lesion may
be helpful in timely investigation and accurate diagnosis of stroke etiology.
PMID- 25112557
TI - The prevalence and subjective handicap of epilepsy in Ilie--a rural riverine
community in South West Nigeria: a door-to-door survey.
AB - BACKGROUND: The prevalence of epilepsy is high in tropical countries,
particularly in Africa with an estimated mean prevalence of 15 per 1000. There is
lack of recent data on epilepsy prevalence in Nigeria. The main objective of this
study was to determine the prevalence of epilepsy in Ilie in South West (SW)
Nigeria, and the secondary objectives were to determine the clinical
characteristics, the seizure types with electroencephalography (EEG) recording,
the pattern of treatment, and to evaluate the subjective handicap of people with
epilepsy (PWE). MATERIALS AND METHODS: The study, which was descriptive cross
sectional, was carried out in Ilie, a rural community in South West Nigeria,
using a simple random sampling technique. The survey was done in 2 phases from
January 2013 to April 2013. Phase 1: Door-to-door screening using the WHO
Neuroscience Research Protocol to detect neurological disorders by health
workers. Phase 2: Individuals with positive screening had complete neurologic
examination by neurologists as well as an EEG recording. The questionnaires for
survey of epilepsy in tropical countries and subjective handicap of epilepsy were
administered to all PWE. RESULTS: Two thousand two hundred twelve individuals
from 231 households were screened during the first phase, and 33 cases of
neurologic diseases were detected. During the second phase, 10 cases were
confirmed to be epilepsy by neurologists, thus giving a crude lifetime prevalence
of 10/2212=4.5/1000 population (95% CI=2.30-8.04). CONCLUSIONS: The prevalence of
epilepsy in Ilie in South West Nigeria is rather low compared with previous
figures from studies in rural Africa.
PMID- 25112558
TI - Brief postnatal exposure to phenobarbital impairs passive avoidance learning and
sensorimotor gating in rats.
AB - Phenobarbital is the most commonly utilized drug for the treatment of neonatal
seizures. However, mounting preclinical evidence suggests that even brief
exposure to phenobarbital in the neonatal period can induce neuronal apoptosis,
alterations in synaptic development, and long-lasting changes in behavioral
functions. In the present report, we treated neonatal rat pups with phenobarbital
and evaluated behavior in adulthood. Pups were treated initially with a loading
dose (80 mg/kg) on postnatal day (P)7 and with a lower dose (40 mg/kg) on P8 and
P9. We examined sensorimotor gating (prepulse inhibition), passive avoidance, and
conditioned place preference for cocaine when the animals reached adulthood.
Consistent with our previous reports, we found that three days of neonatal
exposure to phenobarbital significantly impaired prepulse inhibition compared
with vehicle-exposed control animals. Using a step-though passive avoidance
paradigm, we found that animals exposed to phenobarbital as neonates and tested
as adults showed significant deficits in passive avoidance retention compared
with matched controls, indicating impairment in associative memory and/or recall.
Finally, we examined place preference conditioning in response to cocaine.
Phenobarbital exposure did not alter the normal conditioned place preference
associated with cocaine exposure. Our findings expand the profile of behavioral
toxicity induced by phenobarbital.
PMID- 25112559
TI - Behavioural weight management programmes for adults assessed by trials conducted
in everyday contexts: systematic review and meta-analysis.
AB - This systematic review and meta-analysis of effectiveness trials comparing
multicomponent behavioural weight management programmes with controls in
overweight and obese adults set out to determine the effectiveness of these
interventions implemented in routine practice. To be included, interventions must
have been multicomponent, delivered by the therapists who would deliver the
intervention in routine practice and in that same context, and must be widely
available or feasible to implement with little additional infrastructure or
staffing. Searches of electronic databases were conducted, and augmented by
screening reference lists and contacting experts (November 2012). Data were
extracted by two reviewers, with mean difference between intervention and control
for 12-month change in weight, blood pressure, lipids and glucose calculated
using baseline observation carried forward. Data were also extracted on adverse
events, quality of life and mood measures. Although there were many published
efficacy trials, only eight effectiveness trials met the inclusion criteria.
Pooled results from five study arms providing access to commercial weight
management programmes detected significant weight loss at 12 months (mean
difference -2.22 kg, 95% confidence interval [CI] -2.90 to -1.54). Results from
two arms of a study testing a commercial programme providing meal replacements
also detected significant weight loss (mean difference -6.83 kg, 95% CI -8.39 to
5.26). In contrast, pooled results from five interventions delivered by primary
care teams showed no evidence of an effect on weight (mean difference -0.45 kg,
95% CI -1.34 to 0.43). One study testing an interactive web-based intervention
detected a significant effect in favour of the intervention at 12 months, but the
study was judged to be at high risk of bias and the effect did not persist at 18
months. Few studies reported other outcomes, limiting comparisons between
interventions. Few trials have examined the effectiveness of behavioural weight
loss programmes delivered in everyday contexts. These trials suggest that
commercial interventions delivered in the community are effective for achieving
weight loss. There is no evidence that interventions delivered within primary
care settings by generalist primary care teams trained in weight management
achieve meaningful weight loss.
PMID- 25112560
TI - Changes in sleep and fatigue in newly treated pediatric oncology patients.
AB - BACKGROUND: Fatigue has been reported as one of the most distressing symptoms in
oncology patients, yet few have investigated the longitudinal course of sleep and
fatigue in newly diagnosed pediatric oncology patients. PROCEDURE: To
longitudinally assess presence and changes of sleep complaints and fatigue, we
administered questionnaires designed to measure sleep complaints, sleep habits,
daytime sleepiness, and fatigue to parents of pediatric oncology patients ages 2
18 and to pediatric oncology patients, themselves, ages 8-18 within 30 days of
diagnosis (n = 170) and again 8 weeks later (n = 153). RESULTS: Bedtimes, wake
times, and sleep duration remained relatively stable across the first 8 weeks of
treatment. Sleep duration and fatigue were not related for the entire sample,
though children's self-reported sleep duration was positively correlated with
fatigue only at the baseline time point. Parent reports of fatigue significantly
decreased for leukemia patients but remained rather high for solid tumor and
brain tumor patients. CONCLUSIONS: Because fatigue remained high for solid tumor
and brain tumor patients across the initial 8 weeks of treatment, this may
highlight the need for intervention in this patient population.
PMID- 25112563
TI - A multicentre, prospective, randomized, controlled study to evaluate the use of a
fibrin sealant as an adjunct to sutured dural repair.
AB - Background. Obtaining intra-operative watertight closure of the dura is
considered important in reducing post-operative cerebrospinal fluid (CSF) leak.
The purpose of this study was to evaluate a fibrin sealant as an adjunct to
sutured dural repair to obtain intra-operative watertight closure in cranial
neurosurgery. Methods. This randomized, controlled multicenter study compared a
fibrin sealant (EVICEL(r) Fibrin Sealant [Human]) to sutured dural closure
(Control). Subjects underwent supratentorial or posterior fossa procedures.
Following primary dural repair by sutures, the closure was evaluated for intra
operative CSF leak by moderately increasing the intracranial pressure. If
present, subjects were randomized to EVICEL(r) or additional sutures (2:1 ratio),
stratified by surgical approach. Following treatment, subjects were successful if
no CSF leaks were present during provocative challenge. Safety was assessed to 30
days post-surgery, including incidence of CSF leakage. Results. One hundred and
thirty-nine subjects were randomized: 89 to EVICEL(r) and 50 to Control. Intra
operative watertight closure was achieved in 92.1% EVICEL(r)-treated subjects
versus 38.0% controls; a treatment difference of 54.1% (p < 0.001). The treatment
differences in the supratentorial and posterior fossa strata were 49.1% and
75.7%, respectively (p < 0.001). The incidence of adverse events was similar
between treatment groups. No deaths or unexpected serious adverse drug reactions
were reported. CSF leakage within 30 days post-operatively was 2.2% and 2.0% in
EVICEL(r) and control groups, respectively. In addition, 2 cases of CSF
rhinorrhoea were observed in the EVICEL(r) group. Although not associated with
the suture line where EVICEL(r) was applied, when combined with the other CSF
leaks, the observed leak rate in the EVICEL(r) group was 4.5%. Conclusions. These
results indicate that EVICEL(r) is effective as an adjunct to dural sutures to
provide watertight closure of the dura mater in cranial surgery. The study
confirmed the safety profile of EVICEL(r).
PMID- 25112562
TI - The relationship between nutritional status, inflammatory markers and survival in
patients with advanced cancer: a prospective cohort study.
AB - BACKGROUND: Malnutrition and elevated inflammatory markers have a negative impact
on clinical outcomes in cancer patients. Few studies have investigated the
associations between inflammatory makers, nutritional status and survival. This
study investigates the association between nutritional status, inflammatory
markers and overall survival (OS) in patients with advanced cancer. METHODS: This
prospective cohort study recruited 114 adult patients from January 2007 to
January 2010. It included patients diagnosed with advanced cancer, good Eastern
Cooperative Oncology Group (ECOG) performance status 0-2, a prognosis of more
than 3 months and had not received chemotherapy for advanced cancer prior to
enrollment. Baseline data were collected prior to commencement of chemotherapy.
Patients were followed up from the date of baseline nutritional assessment until
the date of death or the date that data were last updated, whichever came first.
RESULTS: Malnourished cancer patients had statistically significant higher
concentrations of serum C-reactive protein (CRP), neutrophil-to-lymphocyte ratio
(NLR) or modified Glasgow Prognostic Score (mGPS) prior to starting chemotherapy.
In univariate analyses to predict survival, mGPS 1 or 2 had a hazard ratio (HR)
of 1.81 (95 % confidence interval (CI) 1.13-2.89) and NLR >= 5 had a HR of 1.13
(95 % CI 1.08-4.60) and malnutrition (HR of 1.66 for Patient-Generated Subjective
Global Assessment (PG-SGA) B (95 % CI 1.02-2.71), and HR for severely
malnourished patients (PG-SGA C) was 2.73 (95 % CI 1.50-4.96). CONCLUSIONS:
Inflammatory markers were statistically associated with malnutrition.
Malnutrition and mGPS were significant independent predictors of overall survival
in patients with advanced cancer.
PMID- 25112561
TI - Incidence and predictors of anticipatory nausea and vomiting in Asia Pacific
clinical practice--a longitudinal analysis.
AB - PURPOSE: Some patients experience nausea and/or vomiting (NV) before receipt of
chemotherapy. Our objective was to evaluate the impact of prior chemotherapy
induced NV (CINV) on the incidence of anticipatory NV in later cycles. METHODS:
This multicenter, prospective non-interventional study enrolled chemotherapy
naive adults scheduled to receive highly or moderately emetogenic chemotherapy
(HEC/MEC) for cancer in six Asia Pacific countries, excluding those with emesis
within 24 h before cycle 1 chemotherapy. On day 1 before chemotherapy, patients
answered four questions regarding emesis in the past 24 h, nausea, expectation of
post-chemotherapy nausea, and anxiety in the past 24 h, the latter three scored
from 0-10 (none-maximum). Multivariate logistic regression was used to assess the
impact of prior CINV on anticipatory NV in cycles 2 and 3. RESULTS: Five hundred
ninety-eight patients (59% female) were evaluable in cycle 2 (49% HEC, 51% MEC).
The incidence of anticipatory emesis was low before cycles 2 and 3 (1.5-2.3%).
The incidence of clinically significant anticipatory nausea (score of >=3) was
4.8, 7.9, and 8.3% before cycles 1, 2, and 3, respectively, with adjusted odds
ratio (OR), 3.95 (95% confidence interval (CI), 2.23-7.00; p < 0.001) for
patients with clinically significant nausea in prior cycles, compared with none.
The adjusted ORs for other anticipatory NV endpoints ranged from 4.54-4.74 for
patients with prior CINV. The occurrence of clinically significant anxiety in the
prior cycle also resulted in a significantly increased likelihood of anticipatory
nausea. CONCLUSIONS: These findings highlight the importance of preventing CINV
in cycle 1 to reduce anticipatory NV in subsequent cycles.
PMID- 25112564
TI - The general and mental health of movers to more- and less-disadvantaged socio
economic and physical environments within the UK.
AB - Residential mobility may play an important role in influencing both individual
health, by determining individual exposures to environments, and area health, by
shaping area population composition. This study is the first analysis of
migration within the UK to compare general and mental health among adults by age
group and consider moves between neighbourhoods with different levels of both
socio-economic and physical environment disadvantage. The analysis assesses
122,570 cases from the annual British Household Panel Survey, 1996-2006, based
upon pooled data describing moves between consecutive waves of the survey. It
assesses the rates and binary logistic regression model odds of self-reported
general health and mental health problems of movers and stayers by age group. It
also compares movers between Census Area Statistics wards in the UK with
different levels of Carstairs and Multiple Environmental Deprivation Index
(MEDIx) scores. At all ages, movers had similar or higher odds of poor general
and mental health relative to non-movers. Risk of mental health problems were
particularly elevated among movers and remained significant after adjustment for
socio-demographic variables in most age groups. In adjusted analysis of all
adults odds of poor general and mental health were most elevated among movers to
more socio-economically deprived areas, with the highest odds for mental health
(1.54 95% CI 1.27-1.86). In contrast, risk of poor mental health among total
adults was greatest among movers to better physical environments (1.40 95% CI
1.16-1.70). This study therefore finds little evidence of 'healthy migrant
effects' among recent movers within the UK and suggests movers have particularly
elevated risk of mental health problems. It also indicates that selective
migration may not contribute to poor health found in UK neighbourhoods with
multiple physical environment deprivation. Further analysis should explore why
people with mental health problems are more likely to move to socio-economically
deprived neighbourhoods.
PMID- 25112565
TI - How does mental-physical multimorbidity express itself in lived time and space? A
phenomenological analysis of encounters with depression and chronic physical
illness.
AB - Mental-physical multimorbidity (the co-existence of mental and physical ill
health) is highly prevalent and associated with significant impairments and high
healthcare costs. While the sociology of chronic illness has developed a mature
discourse on coping with long term physical illness the impact of mental and
physical health have remained analytically separated, highlighting the need for a
better understanding of the day-to-day complexities encountered by people living
with mental-physical multimorbidity. We used the phenomenological paradigm of the
lived body to elucidate how the experience of mental-physical multimorbidity
shapes people's lifeworlds. Nineteen people with chronic obstructive pulmonary
disease (COPD) and depression (defined as a score >=8 on depression scale of
Hospital Anxiety and Depression Scale) were recruited from secondary NHS care and
interviewed at their homes. Data were analysed phenomenologically using van
Manen's lifeworld existential framework of the lived body, lived time, lived
space, lived relations. Additionally, we re-analysed data (using the same
framework) collected from 13 people recruited from secondary NHS care with either
COPD, rheumatoid arthritis, heart disease, or type 1 or type 2 diabetes and
depression. The phenomenology of mental-physical multimorbidity was articulated
through embodied and emotional encounters with day-to-day life in four ways: [a]
participants' perception of lived time and lived space contracted; [b] time and
[c] space were experienced as liminal categories, enforcing negative mood and
temporal and spatial contraction; and [d] time and space could also be customised
to reinstate agency and self-determination. Mental-physical multimorbidity
negatively impacts on individuals' perceptions of lived time and lived space,
leading to a loss of agency, heightened uncertainty, and poor well-being.
Harnessing people's capacity to modify their experience of time and space may be
a novel way to support people with mental-physical multimorbidity to live well
with illness.
PMID- 25112566
TI - Fragile health and fragile wealth: mortgage strain among African American
homeowners.
AB - Several recent studies identify illness and disability as contributors to
mortgage strain, suggesting that the disproportionate burden of poor health that
African Americans experience may be an important source of housing fragility in
this population. In order to understand how poor health plays out in the lived
experiences of African-American homeowners and contributes to mortgage strain, we
present an analysis of 28 in-depth interviews conducted with middle and working
class African-American homeowners at risk of losing their homes. Our interviews
show how racial inequalities in health, which result from an ongoing history of
racial discrimination, intersect with other racially stratified sources of
housing fragility to put homeowners at risk of foreclosure. Many participants in
this study were long-term homeowners who experienced mortgage strain as result of
a health-related event that triggered the collapse of a fragile household budget.
Like many middle and working-class African Americans, participants experienced
poor health and disability at relatively young ages. Additionally, they often
lacked access to personal and public safety nets that could buffer the
consequences of illness. Understanding how poor health contributes to mortgage
strain among African-American homeowners provides important insight into the
downstream consequences of health inequalities. Furthermore, understanding the
processes through which illness can act as a financial shock has important policy
implications.
PMID- 25112567
TI - Modeling satisfaction amongst the elderly in different Chinese urban
neighborhoods.
AB - Rapidly aging populations constitute a critical issue for researchers and
policymakers across the world; the challenges of a shifting demographic structure
are particularly pertinent in the case of China. Population control strategies
implemented in China in the late 1970s have substantially changed the social and
demographic structure of Chinese cities and the traditional role of families in
caring for elderly people. To meet the growing needs of elderly residents "aging
in place," age-friendly environments and new types of senior services are
required and encouraged. This research examines the satisfaction of seniors in
relation to the elderly services and living environments available to them,
through empirical studies of six types of neighborhoods in Beijing. Using
structural equation modeling (SEM), a satisfaction model under the Person
Environment Fit (P-E Fit) model framework was developed. This model considered
the senior respondent's health status, economic attributes, family and social
support networks, and neighborhood living environments. Social support was found
to be the primary factor affecting satisfaction amongst the urban elderly in
Beijing. The research also highlights the need to differentiate between different
types of neighborhoods, which can differ significantly in terms of the socio
economic attributes (i.e., family structure, income, and education) of their
senior residents. As such, based on the path coefficients revealed by different
structural equation models of various neighborhoods, four types of neighborhoods
were identified: in Type 1 neighborhoods, the neighborhood environment and the
senior services provided by communities were primary factors in elderly
satisfaction; in Type 2 neighborhoods, the satisfaction of inhabitants was
strongly influenced by personal attributes such as health and income; Type 3
neighborhoods were residence of low-income people where the level of social
support was the foremost factor; and in Type 4, social support and the
environment were both essential.
PMID- 25112568
TI - Predictors of suicides occurring within suicide clusters in Australia, 2004-2008.
AB - A number of studies have investigated the presence of suicide clusters, but few
have sought to identify risk and protective factors of a suicide occurring within
a cluster. We aimed to identify socio-demographic and contextual characteristics
of suicide clusters from national and regional analyses of suicide clusters. We
searched the National Coroners Information System for all suicides in Australia
from 2004 to 2008. Scan statistics were initially used to identify those deaths
occurring within a spatial-temporal suicide cluster during the period. We then
used logistic regression and generalized estimation equations to estimate the
odds of each suicide occurring within a cluster differed by sex, age, marital
status, employment status, Indigenous status, method of suicide and location. We
identified 258 suicides out of 10,176 suicides during the period that we
classified as being within a suicide cluster. When the deceased was Indigenous,
living outside a capital city, or living in the northern part of Australia (in
particular, Northern Territory, Queensland and Western Australia) then there was
an increased likelihood of their death occurring within a suicide cluster. These
findings suggest that suicide clustering might be linked with geographical and
Indigenous factors, which supported sociological explanations of suicide
clustering. This finding is significant for justifying resource allocation for
tackling suicide clustering in particular areas.
PMID- 25112569
TI - Social status and biological dysregulation: the "status syndrome" and allostatic
load.
AB - Data from a national sample of 1255 adults who were part of the MIDUS (Mid-life
in the U.S.) follow-up study and agreed to participate in a clinic-based in-depth
assessment of their health status were used to test the hypothesis that, quite
part from income or educational status, perceptions of lower achieved rank
relative to others and of relative inequality in key life domains would be
associated with greater evidence of biological health risks (i.e., higher
allostatic load). Results indicate that over a variety of status indices
(including, for example, the person's sense of control, placement in the
community rank hierarchy, perception of inequality in the workplace) a syndrome
of perceived relative deprivation is associated with higher levels of biological
dysregulation. The evidence is interpreted in light of the well-established
associations between lower socio-economic status and various clinically
identified health morbidities. The present evidence serves, in effect, both as a
part of the explanation of how socio-economic disparities produce downstream
morbidity, and as an early warning system regarding the ultimate health effects
of currently increasing status inequalities.
PMID- 25112570
TI - Serum-induced neurite retraction in CAD cells--involvement of an ATP-actin
retractile system and the lack of microtubule-associated proteins.
AB - Cultured catecholamine-differentiated cells [which lack the microtubule
associated proteins (MAPs): MAP1B, MAP2, Tau, STOP, and Doublecortin] proliferate
in the presence of fetal bovine serum, and, in its absence, cease dividing and
generate processes similar to the neurites of normal neurons. The reintroduction
of serum induces neurite retraction, and proliferation resumes. The neurite
retraction process in catecholamine-differentiated cells was partially
characterized in this study. Microtubules in the cells were found to be in a
highly dynamic state, and tubulin in the microtubules consisted primarily of the
tyrosinated and deacetylated isotypes. Increased levels of acetylated or Delta2
tubulin (which are normally absent) did not prevent serum-induced neurite
retraction. Treatment of differentiated cells with lysophosphatidic acid or
adenosine deaminase induced neurite retraction. Inhibition of Rho-associated
protein kinase, ATP depletion and microfilament disruption each (individually)
blocked serum-induced neurite retraction, suggesting that an ATP-dependent
actomyosin system underlies the mechanism of neurite retraction. Nocodazole
treatment induced neurite retraction, but this effect was blocked by pretreatment
with the microtubule-stabilizing drug paclitaxel (Taxol). Paclitaxel did not
prevent serum-induced or lysophosphatidic acid-induced retraction, suggesting
that integrity of microtubules (despite their dynamic state) is necessary to
maintain neurite elongation, and that paclitaxel-induced stabilization alone is
not sufficient to resist the retraction force induced by serum. Transfection with
green fluorescent protein-Tau conferred resistance to retraction caused by serum.
We hypothesize that, in normal neurons (cultured or in vivo), MAPs are necessary
not only to stabilize microtubules, but also to establish interactions with other
cytoskeletal or membrane components to form a stable structure capable of
resisting the retraction force.
PMID- 25112571
TI - Functionalized graphene as a nanostructured membrane for removal of copper and
mercury from aqueous solution: a molecular dynamics simulation study.
AB - The purpose of the present study was to investigate the removal of copper and
mercury using functionalized graphene as a nanostructured membrane. The molecular
dynamics simulation method was used to investigate the removal ability of these
ions from aqueous solution using functionalized graphene membrane. The studied
systems included a functionalized graphene membrane which was placed in the
aqueous ionic solution of CuCl2 and HgCl2. An external electrical field was
applied along the z axis of the system. The results indicated that the
application of electrical field on the system caused the desired ions to pass
through the functionalized graphene membrane. The Fluorinated pore (F-pore)
terminated graphene selectively conducted Cu(2+) and Hg(2+) ions. The calculation
of the potential of mean force of ions revealed that Cu(2+) and Hg(2+) ions face
a relatively small energy barrier and could not pass through the F-pore graphene
unless an external electrical field was applied upon them. In contrast, the
energy barrier for the Cl(-) ion was large and it could not pass through the F
pore graphene. The findings of the study indicate that the permeation of ions
across the graphene was a function of applied electrical fields. The findings of
the present study are based on the detailed analysis and consideration of
potential of mean force and radial distribution function curves.
PMID- 25112572
TI - India must act to stem rise of unnecessary medical interventions, says World
Bank.
PMID- 25112573
TI - Elevated prenatal methylmercury exposure in Nigeria: evidence from maternal and
cord blood.
AB - Methylmercury is a neurodevelopmental toxicant that is globally distributed
though little is known about prenatal exposures in sub-Saharan Africa. The
objective of the current study was to measure total mercury levels in cord blood
and maternal blood from 95 mother-newborn pairs recruited from hospitals in
Nnewi, Nigeria. The secondary aims of the study were to explore if demographic
and dietary factors were associated with blood mercury levels, and to explore if
mercury levels were associated with any self-reported health outcome and
childbirth outcome. Maternal blood mercury levels averaged 3.6 MUg L(-1) and
ranged from 1.1 MUg L(-1) to 9.5 MUg L(-1). Cord blood mercury averaged 5.1 MUg
L(-1) and ranged from 1.2 MUg L(-1) to 10.6 MUg L(-1). The mean ratio of mercury
in paired cord blood to maternal blood was 1.5 and it ranged from 0.4 to 3.2.
Mercury in maternal and cord blood were significantly correlated (r=0.471). More
than one-third of mothers reported eating fish at least once per day, and a weak
(p=0.08) fish consumption-related increase in blood mercury was found. Cord blood
mercury was positively and significantly associated with birth weight and length,
and head and chest circumference. Mercury levels in 36% of the participants
exceeded the biomonitoring guideline associated with the United States
Environmental Protection Agency (U.S. EPA) reference dose for mercury. The study
shows that pregnant women and their newborns are exposed to methylmercury and
that their exposures are higher compared to general populations sampled from
other regions of the world.
PMID- 25112574
TI - Sensitivity of the sea snail Gibbula umbilicalis to mercury exposure--linking
endpoints from different biological organization levels.
AB - Mercury contamination is a common phenomenon in the marine environment and for
this reason it is important to develop cost-effective and relevant tools to
assess its toxic effects on a number of different species. To evaluate the
possible effects of Hg in the sea snail Gibbula umbilicalis, animals were exposed
to increasing concentrations of the contaminant in the ionic form for 96 h. After
this exposure period, mortality, feeding and flipping behavior, the activity of
the biomarkers glutathione S-transferase, superoxide dismutase, catalase, lactate
dehydrogenase and cholinesterase, the levels of lipid peroxidation and cellular
energy allocation were measured. After 96 h of exposure to the highest Hg
concentration (~LC20), there was a significant inhibition of the cholinesterase
activity as well as impairment in the flipping behavior and post-exposure feeding
of the snails. Cholinesterase inhibition was correlated with the impairment of
behavioral responses also caused by exposure to Hg. These endpoints, including
the novel flipping test, revealed sensitivity to Hg and might be used as relevant
early warning indicators of prospective effects at higher biological organization
levels, making these parameters potential tools for environmental risk
assessment. The proposed test species showed sensitivity to Hg and proved to be a
suitable and resourceful species to be used in ecotoxicological testing to assess
effects of other contaminants in marine ecosystems.
PMID- 25112575
TI - Effects of molecular weight on the diffusion coefficient of aquatic dissolved
organic matter and humic substances.
AB - In situ measurements of labile metal species using diffusive gradients in thin
films (DGT) passive samplers are based on the diffusion rates of individual
species. Although most studies have dealt with chemically isolated humic
substances, the diffusion of dissolved organic matter (DOM) across the hydrogel
is not well understood. In this study, the diffusion coefficient (D) and
molecular weight (MW) of 11 aquatic DOM and 4 humic substances (HS) were
determined. Natural, unaltered aquatic DOM was capable of diffusing across the
diffusive gel membrane with D values ranging from 2.48*10(-6) to 5.31*10(-6)
cm(2) s(-1). Humic substances had diffusion coefficient values ranging from
3.48*10(-6) to 6.05*10(-6) cm(2) s(-1), congruent with previous studies.
Molecular weight of aquatic DOM and HS samples (~500-1750 Da) measured using
asymmetrical flow field-flow fractionation (AF4) strongly influenced D, with
larger molecular weight DOM having lower D values. No noticeable changes in DOM
size properties were observed during the diffusion process, suggesting that DOM
remains intact following diffusion across the diffusive gel. The influence of
molecular weight on DOM mobility will assist in further understanding and
development of the DGT technique and the uptake and mobility of contaminants
associated with DOM in aquatic environments.
PMID- 25112576
TI - Long-term manure application effects on phosphorus speciation, kinetics and
distribution in highly weathered agricultural soils.
AB - Phosphorus (P) K-edge XANES and Fe K-edge EXAFS spectroscopies along with
sequential P chemical fractionation and desorption kinetics experiments, were
employed to provide micro- and macro-scale information on the long-term fate of
manure application on the solid-state speciation, kinetics and distribution of P
in highly weathered agricultural soils of southern Brazil. Soil test P values
ranged from 7.3 up to 16.5 times as much higher than the reference soil. A sharp
increase in amorphous Fe and Al amounts were observed as an effect of the
consecutive application of manures. Whereas our results showed that the P
sorption capacity of some manured soils was not significantly affected, P risk
assessment indices indicated that P losses should be expected, likely due to the
excessive manure rates applied to the soils. The much higher contents of
amorphous Fe and Al (hydr)oxides (55% and 80% increase with respect to the
reference soil, respectively) in manured soils seem to have counterbalanced the
inhibiting effect of soil organic matter on P sorption by creating additional P
sorption sites. Accordingly, the newly created P sorbing surfaces were important
to prevent an even larger P loss potential. Phosphorus K-edge XANES lent
complimentary hints on the loss of crystallinity and transformation of originally
present Fe-P minerals into poorly crystalline ones as an effect of manuring,
whereas Fe K-edge EXAFS provided insights into the structural changes underwent
in the soils upon manure application and soil management.
PMID- 25112577
TI - Monitoring bisphenol A and its biodegradation in water using a fluorescent
molecularly imprinted chemosensor.
AB - In this paper, we present a simple and rapid method for monitoring bisphenol A
(BPA) and its biodegradation in environmental water using a fluorescent
molecularly imprinted polymer chemosensor (fMIPcs). A fluorescent molecularly
imprinted polymer (fMIP) was first synthesized by precipitation polymerization
method using BPA as template, dansyl methacrylate as functional monomer. Then a
fMIPcs was constructed by combining the fMIP with a fluorescent microplate
reader. The fMIPcs displayed selective, concentration-dependent fluorescence
quenching in response to BPA in water even in the existence of interferences,
thereby allowing reliable high through-put quantification of BPA via simple
fluorescence measurements. The fMIPcs was able to directly quantify BPA (from 10
to 2000 MUg L(-1)) in different environmental water samples (distilled water,
distilled water containing heavy metals and humic acid, tap water, and river
water) with high accuracy, and to monitor BPA biodegradation in real-time. Using
the fMIPcs, it was possible to achieve fast analytical results with lower limit
of detection for BPA (3 MUg L(-1)) from smaller sample volume (250 MUL), which
are superior to many relevant methods reported in the literature. Moreover, BPA
levels and biodegradation rates measured by fMIPcs are comparable to the
instrument-based method (HPLC). The fMIPcs developed in this work offers a new
solution for simple, rapid, accurate and high through-put BPA quantification, and
makes it possible to monitor BPA biodegradation in real time.
PMID- 25112578
TI - Transport via xylem and accumulation of aflatoxin in seeds of groundnut plant.
AB - Aflatoxin contamination in groundnut seeds in the absence of any aflatoxigenic
fungi leads to a hypothesis that aflatoxins are present naturally in soil and is
transferred to seeds through uptake by roots. A survey was conducted on the
natural occurrence of aflatoxins in agricultural soils, among nine main groundnut
growing regions of Karnataka state, India. All 71 soil samples collected in this
survey were contaminated with aflatoxins esp. AFB1. An in vitro xylem sap
experiment proved the ability of groundnut plant roots to absorb AFB1, and
transport to aerial plant parts via the xylem. Hydroponics experiment also proved
the uptake of AFB1 by the roots and their translocation to shoot. Uptake was
affected by the initial concentration of toxin and pH of the medium. Among the 14
varieties screened, GPBD4 and MLT.K.107 (III) recorded highest and least AFB1
uptake, respectively. The above results were validated using a greenhouse
experiment. Here, the aflatoxin absorbed by root gradually transferred to shoot
that was later found in seeds towards the end of experiment. Thus, the groundnut
seeds can also get contaminated with aflatoxin by direct uptake of aflatoxin
through conducting tissue in addition to fungal infection. The present study
revealed the novel mode of aflatoxin contamination in groundnut seeds without
fungal infection.
PMID- 25112579
TI - Characteristics and sources of atmospheric mercury speciation in a coastal city,
Xiamen, China.
AB - Semi-continental monitoring of gaseous elemental mercury (GEM), particulate
mercury (Hgp), and reactive gaseous mercury (RGM) was conducted in the Institute
of Urban Environment, CAS in Xiamen, China from March 2012 to February 2013. The
average concentrations and relative standard deviations (RSD) were 3.50 (34.6%)
ng m(-3), 174.41 (160.9%) pg m(-3), and 61.05 (113.7%) pg m(-3) for GEM, Hgp, and
RGM, respectively. The higher concentrations of GEM and Hgp were observed in
spring and winter months, indicating the combustion source, while RGM showed the
different seasonal variation with highest concentration in spring and the minimum
value in winter. The concentrations of Hg species were generally elevated in
nighttime and low in daytime to reflect the diurnal changes in meteorology,
especially the mixing condition of the air masses. The high Hg concentrations
were observed in SWW-NW sectors due to calm wind while the low levels in NE-SE
due to high speed wind, and the amplitude was much larger for Hgp and RGM.
Backward trajectories calculation indicated that summer air masses were much more
from ocean with lower Hg while the air masses were mainly from inland area in
other seasons. Principal component analysis suggested that combustion and road
traffic emissions were the dominant anthropogenic mercury sources for the study
area, and the temporal distribution of atmospheric mercury was mainly the result
of climatological change.
PMID- 25112580
TI - Use of multiple regression models to evaluate the formation of halonitromethane
via chlorination/chloramination of water from Tai Lake and the Qiantang River,
China.
AB - The deterioration of water quality, especially organic pollution in Tai Lake and
the Qiantang River, have recently received attention in China. The objectives of
this study were to evaluate the formation of halonitromethanes (HNMs) using
multiple regression models for chlorination and chloramination and to identify
the key factors that influence the formation of HNMs in Tai Lake and the Qiantang
River. The results showed that the total formation of HNMs (T-HNMs) during
chlorination and chloramination could be described using the following models:
(1) [Formula: see text] =(10)(5.267)(DON)(6.645)(Br(-))(0.737)(DOC)(
)(5.537)(Cl2)(0.333)(t)(0.165) (R(2)=0.974, p<0.01, n=33), and (2) T
HNMNH2Cl=(10)(-)(2.481)(Cl2)(0.451)(NO2(-))(0.382)(Br(
))(0.630)(t)(0.640)(Temp)(0.581) (R(2)=0.961, p<0.05, n=33), respectively. The
key factors that influenced the T-HNM yields during chlorination were dissolved
organic nitrogen (DON), bromide and dissolved organic carbon (DOC). The nitrite
and bromide concentrations and the reaction time mainly affected the T-HNM yields
during chloramination. Additional analysis indicated that the bromine
incorporation factors (BIFs) for trihalogenated HNMs generally decreased as the
chlorine/chloramine dose, temperature and reaction time decreased and increased
as the bromide concentration increased.
PMID- 25112581
TI - A colorimetric DET technique for the high-resolution measurement of two
dimensional alkalinity distributions in sediment porewaters.
AB - Measurements of porewater alkalinity are fundamental to the study of organic
matter mineralization in sediments, which plays an essential role in the global
cycles of carbon and nutrients. A new colorimetric diffusive equilibration in
thin film (DET) technique is described for measuring two-dimensional total
alkalinity distributions in sediment porewaters at high resolution (1-2 mm(2)).
Thin polyacrylamide hydrogel layers (0.8 mm) equilibrate with the porewater and,
after removal, are immediately laid onto another hydrogel containing formic acid,
which reacts with alkalinity-generating species, and the pH-indicator bromophenol
blue. The resultant color change is quantified using computer-imaging
densitometry. The lower limit of detection is 0.2 meq L(-1) and the upper
measurement limit is 8 meq L(-1). Deployment in seagrass colonized sediment
revealed high levels of spatial heterogeneity in the porewater alkalinity
distribution, with concentrations ranging from 2.28 meq L(-1) in the overlying
water to 5.13 meq L(-1) in some parts of the sediment. This is the first time
that two-dimensional, high-resolution distributions of porewater alkalinity have
been measured.
PMID- 25112583
TI - Introduction. Fertilization and early development.
PMID- 25112582
TI - Avian feathers as a non-destructive bio-monitoring tool of trace metals
signatures: a case study from severely contaminated areas.
AB - The concentrations of trace metals were assessed using feathers of cattle egrets
(Bubulcus ibis), collected within two industrial areas of Pakistan, Lahore and
Sialkot. We found, in order of descending concentration: Zinc (Zn), Iron (Fe),
Nickel (Ni), Copper (Cu), Cadmium (Cd), and Manganese (Mn), Chromium (Cr),
Arsenic (As), and Lithium (Li), without any significant difference (except Fe,
Zn, and Ni) between the two areas. The concentrations of trace metals, we
recorded were among the highest ever reported in the feathers of avian species
worldwide. The concentrations of Cr, Pb, Cd were above the threshold that affects
bird reproductive success. The high contamination by heavy metals in the two
areas is due to anthropogenic activities as well to natural ones (for As and Fe).
The bioaccumulation ratios in eggs and feathers of the cattle egret, their prey,
and the sediments from their foraging habitats, confirmed that avian feathers are
a convenient and non-destructive sampling tool for the metal contamination. The
results of this study will contribute to the environmental management of the
Lahore and Sialkot industrial areas.
PMID- 25112585
TI - Guided imagery for postoperative pain, energy healing for quality of life,
probiotics for acute diarrhea in children, acupuncture for postoperative nausea
and vomiting, and animal-assisted therapy for mental disorders.
PMID- 25112584
TI - Randomised clinical trial: the long-term safety and tolerability of naloxegol in
patients with pain and opioid-induced constipation.
AB - BACKGROUND: Opioid-induced constipation (OIC) is a common adverse effect of
opioid therapy. AIM: To evaluate the long-term safety and tolerability of
naloxegol, an oral, peripherally acting MU-opioid receptor antagonist (PAMORA),
in patients with noncancer pain and OIC. METHODS: A 52-week, multicenter, open
label, randomised, parallel-group phase 3 study was conducted in out-patients
taking 30-1000 morphine-equivalent units per day for >=4 weeks. Patients were
randomised 2:1 to receive naloxegol 25 mg/day or usual-care (UC; investigator
chosen laxative regimen) treatment for OIC. RESULTS: The safety set comprised 804
patients (naloxegol, n = 534; UC, n = 270). Mean exposure duration was 268 days
with naloxegol and 297 days with UC. Frequency of adverse events (AEs) was 81.8%
with naloxegol and 72.2% with UC. Treatment-emergent AEs occurring more
frequently for naloxegol vs. UC were abdominal pain (17.8% vs. 3.3%), diarrhoea
(12.9% vs. 5.9%), nausea (9.4% vs. 4.1%), headache (9.0% vs. 4.8%), flatulence
(6.9% vs. 1.1%) and upper abdominal pain (5.1% vs. 1.1%). Most naloxegol-emergent
gastrointestinal AEs occurred early, resolving during or after naloxegol
discontinuation and were mild or moderate in severity; 11 patients discontinued
due to diarrhoea and nine patients owing to abdominal pain. Pain scores and mean
daily opioid doses remained stable throughout the study; no attributable opioid
withdrawal AEs were observed. Two patients in each group had an adjudicated major
adverse cardiovascular event unrelated to study drug; no AEs were reported nor
adjudicated as bowel perforations. CONCLUSION: In patients with noncancer pain
and opioid-induced constipation, naloxegol 25 mg/day up to 52 weeks was generally
safe and well tolerated.
PMID- 25112586
TI - Predicting invasive breast cancer versus DCIS in different age groups.
AB - BACKGROUND: Increasing focus on potentially unnecessary diagnosis and treatment
of certain breast cancers prompted our investigation of whether clinical and
mammographic features predictive of invasive breast cancer versus ductal
carcinoma in situ (DCIS) differ by age. METHODS: We analyzed 1,475 malignant
breast biopsies, 1,063 invasive and 412 DCIS, from 35,871 prospectively collected
consecutive diagnostic mammograms interpreted at University of California, San
Francisco between 1/6/1997 and 6/29/2007. We constructed three logistic
regression models to predict the probability of invasive cancer versus DCIS for
the following groups: women >= 65 (older group), women 50-64 (middle age group),
and women < 50 (younger group). We identified significant predictors and measured
the performance in all models using area under the receiver operating
characteristic curve (AUC). RESULTS: The models for older and the middle age
groups performed significantly better than the model for younger group (AUC =
0.848 vs, 0.778; p = 0.049 and AUC = 0.851 vs, 0.778; p = 0.022, respectively).
Palpability and principal mammographic finding were significant predictors in
distinguishing invasive from DCIS in all age groups. Family history of breast
cancer, mass shape and mass margins were significant positive predictors of
invasive cancer in the older group whereas calcification distribution was a
negative predictor of invasive cancer (i.e. predicted DCIS). In the middle age
group--mass margins, and in the younger group--mass size were positive predictors
of invasive cancer. CONCLUSIONS: Clinical and mammographic finding features
predict invasive breast cancer versus DCIS better in older women than younger
women. Specific predictive variables differ based on age.
PMID- 25112588
TI - The relationship between urotensin II and its receptor and the
clinicopathological parameters of breast cancer.
AB - BACKGROUND: Urotensin II is a vasoactive polypeptide. It is known that some
vasoactive polypeptides are produced and secreted by tumor cells, and act as a
paracrine growth stimulant. The aim of this study was to examine the relationship
between urotensin II and its receptor's messenger RNA expression in breast
cancer. MATERIAL/METHODS: Fifty-nine women with breast cancer were included in
this study. The median age was 48 years. The relationships between urotensin II
and urotensin II receptor mRNA expressions, which were derived from fresh breast
cancer tissues and adjacent normal breast tissues, and clinical and pathological
parameters, were assessed. RESULTS: We found expressions of urotensin II mRNA and
its receptor in 55 of 59 breast cancer tissues and in 55 of 59 normal breast
tissues. We found a positive significant correlation between urotensin II and its
receptor (p=0.001, r=0.632), and found a negative, but insignificant, correlation
between urotensin II and age (p=0.038, r=-0.281). Urotensin II levels were higher
in the premenopausal group compared to the postmenopausal group (p<0.05). The
mean urotensin II receptor expression was higher in the premenopausal group
(p<0.05) compared to the postmenopausal group, and its expression was also higher
in the group without extra-nodal invasion compared to that of the group with
extra-nodal invasion (p=0.001). Urotensin II levels were higher in the group
without lymphatic invasion compared to the group with lymphatic invasion
(p=0.048). CONCLUSIONS: This study is the first in the English medical literature
to determine the urotensin II and its receptor mRNA expressions in breast cancer
tissues. Consequently, urotensin II seems be associated with menopausal status,
and extra-nodal and lymphatic invasion.
PMID- 25112590
TI - Uterine morcellation at the time of hysterectomy: techniques, risks, and
recommendations.
AB - IMPORTANCE: Uterine leiomyomata or fibroids are the most common pelvic tumor
experienced in women. A minimally invasive approach to hysterectomy has proven
benefits of cosmesis, lower blood loss, less pain, decreased hospital stay, and
faster recovery. The incidence of uterine morcellation, the process of making a
uterine specimen smaller for purposes of removal via a minimally invasive
approach, has increased for this reason. OBJECTIVE: We review the history,
techniques, and direct and indirect risks described in the literature,
recommendations for appropriate use, and how to counsel patients regarding this
procedure. EVIDENCE ACQUISITION: A thorough search of PubMed for all current
literature was performed. Techniques for morcellation were reviewed. We included
studies that addressed the type and incidence of morcellator-associated risks
including those addressing the incidence of leiomyosarcoma in patients with
presumed uterine fibroids. RESULTS: We have summarized several techniques to aid
the practitioner in performing morcellation procedures and the risks involved. We
have summarized all of the current consensus statements regarding the
recommendations for use of morcellation and the approach to proper counseling.
CONCLUSIONS AND RELEVANCE: Morcellation is an effective method of specimen
removal that can decrease the need for laparotomy in both benign and malignant
conditions. Upon analysis of current data and consensus statements, when
possible, morcellation should be performed within a contained environment to
minimize any potential tumor spread in the event of an undiagnosed malignancy.
Patients should be adequately counseled to make an informed decision regarding
undergoing a morcellation procedure. Future methods for enclosed specimen
extraction will hopefully change the future of morcellation.
PMID- 25112553
TI - [Patient's care and management of dyslipidemia in type 2 diabetic patients in the
clinical practice in Spain: The LIPEDIA study].
AB - INTRODUCTION: Treatment of atherogenic dyslipidemia (AD) in type 2 diabetes (DM2)
should focus on the global control of dyslipidemia. The aim of this study was to
determine how hospital (MSs) and primary care specialist (GPs) from Spain manage
AD in DM2 during their daily practice. METHODS: An observational, cross
sectional, multicentric study was conducted. Information about daily practice was
obtained from 497 MSs and 872 GPs across Spain. RESULTS: 66% of MSs and 30.5% of
GPs considered DM2 patients to be high-risk. Most consider the c-LDL targets
based on European guidelines. The statins most widely used are atorvastatin and
simvastatin. However both MSs and GPs considered rosuvastatin to be the most
appropriate statin for these patients. 82% of MSs and 68% of GPs considered that
>50% of their patients achieved the c-LDL target. The main reasons of not
achieving this target were lack of treatment adherence and pressure from the
administration. Seventy four percent of MSs reported that there are no common
clinical protocols with GPs. CONCLUSIONS: The differences in the perception of
the real cardiovascular risk of the patient, low use of more appropriate statins,
lack of adherence and poor perception of real c-LDL control may contribute to the
failure in achieving lipid targets in DM2.
PMID- 25112591
TI - The surgical management of cervical cancer: an overview and literature review.
AB - IMPORTANCE: Surgery has evolved into the standard therapy for nonbulky carcinoma
of the cervix. The mainstay of surgical management is radical hysterectomy;
however, less radical procedures have a small but important role in the
management of cervical tumors. OBJECTIVE: Our objective was to discuss the
literature behind the different procedures utilized in the management of cervical
cancer, emphasizing the radical hysterectomy. In addition, we aimed to discuss
ongoing trials looking at the utility of less radical surgeries as well as
emerging technologies in the management of this disease. EVIDENCE ACQUISITION: We
performed a PubMed literature search for articles in the English language that
pertained to the topic of surgical techniques and their outcomes in the treatment
of cervical cancer. RESULTS: The minimally invasive approaches to radical
hysterectomy appear to reduce morbidity without affecting oncological outcomes,
although further data are needed looking at long-term outcomes with the robotic
platform. Trials are currently ongoing looking at the role of less radical
surgery for patients with low-risk disease and the feasibility of sentinel lymph
node mapping. CONCLUSIONS AND RELEVANCE: Radical hysterectomy with pelvic
lymphadenectomy has evolved into the standard therapy for nonbulky disease, and
there is a clear advantage in the use of minimally invasive techniques to perform
these procedures. However, pending ongoing trials, less radical surgery in
patients with low-risk invasive disease as well as sentinel lymph node mapping
may emerge as standards of care in selected patients with cervical carcinoma.
PMID- 25112589
TI - Summary of international guidelines for physical activity after pregnancy.
AB - Postpartum physical activity can improve mood, maintain cardiorespiratory
fitness, improve weight control, promote weight loss, and reduce depression and
anxiety. This review summarizes current guidelines for postpartum physical
activity worldwide. PubMed (MEDLINE) was searched for country-specific government
and clinical guidelines on physical activity after pregnancy through the year
2013. Only the most recent guideline was included in the review. An abstraction
form facilitated extraction of key details and helped to summarize results. Six
guidelines were identified from 5 countries (Australia, Canada, Norway, United
Kingdom, and United States). All guidelines were embedded within pregnancy
related physical activity recommendations. All provided physical activity advice
related to breastfeeding and 3 remarked about physical activity after cesarean
delivery. Recommended physical activities mentioned in the guidelines included
aerobic (3/6), pelvic floor exercise (3/6), strengthening (2/6), stretching
(2/6), and walking (2/6). None of the guidelines discussed sedentary behavior.
The guidelines that were identified lacked specificity for physical activity.
Greater clarity in guidelines would be more useful to both practitioners and the
women they serve. Postpartum physical activity guidelines have the potential to
assist women to initiate or resume physical activity after childbirth so that
they can transition to meeting recommended levels of physical activity. Health
care providers have a critical role in encouraging women to be active at this
time, and the availability of more explicit guidelines may assist them to
routinely include physical activity advice in their postpartum care.
PMID- 25112592
TI - To boldly go.
PMID- 25112594
TI - Successful aging and subjective well-being among oldest-old adults.
AB - PURPOSE OF THE STUDY: This research integrates successful aging and developmental
adaptation models to empirically define the direct and indirect effects of 2
distal (i.e., education and past life experiences) and 5 proximal influences
(i.e., physical functioning, cognitive functioning, physical health impairment,
social resources, and perceived economic status) on subjective well-being. The
proximal influences involved predictors outlined in most extant models of
successful aging (e.g., Rowe & Kahn, 1998 [Rowe, J. W., & Kahn, R. L. (1998).
Successful aging. New York: Pantheon Books.]). Our model extends such models by
including distal impact as well as interactions between distal and proximal
impacts. DESIGN AND METHODS: Data were obtained from 234 centenarians and 72
octogenarians in the Georgia Centenarian Study. Structural equation modeling was
conducted with Mplus 6.1. RESULTS: Results showed significant direct effects of
physical health impairment and social resources on positive aspects of subjective
well-being among oldest-old adults. We also found significant indirect effects of
cognitive functioning and education on positive affect among oldest-old adults.
Social resources mediated the relationship between cognitive functioning and
positive affect; and cognitive functioning and social resources mediated the
relationship between education and positive affect. In addition, physical health
impairment mediated the relationship between cognitive functioning and positive
affect; and cognitive functioning and physical health impairment mediated the
relationship between education and positive affect. IMPLICATIONS: Integrating 2
different models (i.e., successful aging and developmental adaptation) provided a
comprehensive view of adaptation from a developmental perspective.
PMID- 25112596
TI - Combination of material flow analysis and substance flow analysis: a powerful
approach for decision support in waste management.
AB - The novelty of this paper is the demonstration of the effectiveness of combining
material flow analysis (MFA) with substance flow analysis (SFA) for decision
making in waste management. Both MFA and SFA are based on the mass balance
principle. While MFA alone has been applied often for analysing material flows
quantitatively and hence to determine the capacities of waste treatment
processes, SFA is more demanding but instrumental in evaluating the performance
of a waste management system regarding the goals "resource conservation" and
"environmental protection". SFA focuses on the transformations of wastes during
waste treatment: valuable as well as hazardous substances and their
transformations are followed through the entire waste management system. A
substance-based approach is required because the economic and environmental
properties of the products of waste management - recycling goods, residues and
emissions - are primarily determined by the content of specific precious or
harmful substances. To support the case that MFA and SFA should be combined, a
case study of waste management scenarios is presented. For three scenarios, total
material flows are quantified by MFA, and the mass flows of six indicator
substances (C, N, Cl, Cd, Pb, Hg) are determined by SFA. The combined results are
compared to the status quo in view of fulfilling the goals of waste management.
They clearly point out specific differences between the chosen scenarios,
demonstrating potentials for improvement and the value of the combination of
MFA/SFA for decision making in waste management.
PMID- 25112595
TI - An agent-based simulation model for Clostridium difficile infection control.
AB - BACKGROUND: Control of Clostridium difficile infection (CDI) is an increasingly
difficult problem for health care institutions. There are commonly recommended
strategies to combat CDI transmission, such as oral vancomycin for CDI treatment,
increased hand hygiene with soap and water for health care workers, daily
environmental disinfection of infected patient rooms, and contact isolation of
diseased patients. However, the efficacy of these strategies, particularly for
endemic CDI, has not been well studied. The objective of this research is to
develop a valid, agent-based simulation model (ABM) to study C. difficile
transmission and control in a midsized hospital. METHODS: We develop an ABM of a
midsized hospital with agents such as patients, health care workers, and
visitors. We model the natural progression of CDI in a patient using a Markov
chain and the transmission of CDI through agent and environmental interactions.
We derive input parameters from aggregate patient data from the 2007-2010
Wisconsin Hospital Association and published medical literature. We define a
calibration process, which we use to estimate transition probabilities of the
Markov model by comparing simulation results to benchmark values found in
published literature. RESULTS: In a comparison of CDI control strategies
implemented individually, routine bleach disinfection of CDI-positive patient
rooms provides the largest reduction in nosocomial asymptomatic colonization
(21.8%) and nosocomial CDIs (42.8%). Additionally, vancomycin treatment provides
the largest reduction in relapse CDIs (41.9%), CDI-related mortalities (68.5%),
and total patient length of stay (21.6%). CONCLUSION: We develop a generalized
ABM for CDI control that can be customized and further expanded to specific
institutions and/or scenarios. Additionally, we estimate transition probabilities
for a Markov model of natural CDI progression in a patient through calibration.
PMID- 25112597
TI - Transformation of membrane nanosurface of red blood cells under hemin action.
AB - Hemin is the product of hemoglobin oxidation. Some diseases may lead to a
formation of hemin. The accumulation of hemin causes destruction of red blood
cells (RBC) membranes. In this study the process of development of topological
defects of RBC membranes within the size range from nanoscale to microscale
levels is shown. The formation of the grain-like structures in the membrane
("grains") with typical sizes of 120-200 nm was experimentally shown. The process
of formation of "grains" was dependent on the hemin concentration and incubation
time. The possible mechanism of membrane nanostructure alterations is proposed.
The kinetic equations of formation and transformation of small and medium
topological defects were analyzed. This research can be used to study the cell
intoxication and analyze the action of various agents on RBC membranes.
PMID- 25112598
TI - The association of dorsiflexion flexibility on knee kinematics and kinetics
during a drop vertical jump in healthy female athletes.
AB - PURPOSE: While previous studies have examined the association between ankle
dorsiflexion flexibility and deleterious landing postures, it is not currently
known how landing kinetics are influenced by ankle dorsiflexion flexibility. The
purpose of this study was to examine whether ankle dorsiflexion flexibility was
associated with landing kinematics and kinetics that have been shown to increase
the risk of anterior cruciate ligament (ACL) injury in female athletes. METHODS:
Twenty-three female collegiate soccer players participated in a preseason
screening that included the assessment of ankle dorsiflexion flexibility and
lower-body kinematics and kinetics during a drop vertical jump task. RESULTS: The
results demonstrated that females with less ankle dorsiflexion flexibility
exhibited greater peak knee abduction moments (r = -.442), greater peak knee
abduction angles (r = .355), and less peak knee flexion angles (r = .385) during
landing. The range of dorsiflexion flexibility for the current study was between
9 degrees and 23 degrees (mean = 15.0 degrees ; SD 3.9 degrees ). CONCLUSION:
Dorsiflexion flexibility may serve as a useful clinical measure to predict poor
landing postures and external forces that have been associated with increased
knee injury risk. Rehabilitation specialists can provide interventions aimed at
improving dorsiflexion flexibility in order to ameliorate the impact of this
modifiable factor on deleterious landing kinematics and kinetics in female
athletes. LEVEL OF EVIDENCE: II.
PMID- 25112600
TI - Memory factors in Rey AVLT: Implications for early staging of cognitive decline.
AB - Supraspan verbal list learning is widely used to assess dementia and related
cognitive disorders where declarative memory deficits are a major clinical sign.
While the overall learning rate is important for diagnosis, serial position
patterns may give insight into more specific memory processes in patients with
cognitive impairment. This study explored these patterns in a memory clinic
clientele. One hundred eighty three participants took the Rey Auditory-Verbal
Learning Test (RAVLT). The major groups were patients with Alzheimer's disease
(AD), Vascular Dementia (VD), Mild Cognitive Impairment (MCI), and Subjective
Cognitive Impairment (SCI) as well as healthy controls (HC). Raw scores for the
five trials and five serial partitions were factor analysed. Three memory factors
were found and interpreted as Primacy, Recency, and Resistance to Interference.
AD and MCI patients had impaired scores in all factors. SCI patients were
significantly impaired in the Resistance to Interference factor, and in the
Recency factor at the first trial. The main conclusion is that serial position
data from word list testing reflect specific memory capacities which vary with
levels of cognitive impairment.
PMID- 25112599
TI - Sensation seeking predicting growth in adolescent problem behaviors.
AB - There is limited literature on the relationship between sensation seeking and
adolescent risk behaviors, particularly among African Americans. We tested the
association between psychometrically-derived subscales of the Zuckerman Sensation
Seeking Scale and the intercepts and slopes of individual growth curves of
conduct problems, sexual risk taking, and substance use from ages 13 to 18 years
by sex. Boys and girls had different associations between sensation seeking and
baseline levels and growth of risk behaviors. The Pleasure Seeking scale was
associated with baseline levels of conduct problems in boys and girls, baseline
substance use in boys, and growth in sexual risk taking and substance use by
girls. Girls had the same pattern of associations with the Danger/Novelty scale
as the Pleasure Seeking scale. Knowledge about the relationships between
adolescent risk taking and sensation seeking can help in the targeted design of
prevention and intervention programs for the understudied population of very low
income, African American adolescents.
PMID- 25112602
TI - Cartilage polysaccharide induces apoptosis in K562 cells through a reactive
oxygen species-mediated caspase pathway.
AB - In this study, a polysaccharide (PS) was successfully extracted from porcine
cartilage and its effect on chronic myeloid leukemia was examined using human
K562 cells. The results of cell proliferation assays indicated that the PS
inhibited cancer cell growth at different concentrations. Morphological and
biochemical changes characteristic of apoptosis were observed and confirmed by PI
staining and TUNEL assay. The nuclear DNA, RNA and proteins of the cancer cells
subjected to PS treatment were irreversibly destroyed by reactive oxygen species
(ROS), additionally, the ROS effected on the cells directly. The apoptotic
signals altered the permeability of the mitochondrial outer membrane, thereby
resulted in the release of apoptotic factors into the cytoplasm that induced
apoptosis. As caspase-3/7, 8 and 9 were expressed, it was speculated that both
intrinsic and extrinsic pathways were involved in the PS-induced apoptosis.
PMID- 25112603
TI - Prevalence of tonsillar human papillomavirus infections in Denmark.
AB - The incidence of tonsillar carcinomas associated with Human Papillomavirus (HPV)
infection has increased dramatically over the last three decades. In fact,
currently in Scandinavia, HPV-associated cases account for over 80 % of tonsillar
carcinoma cases. Yet, the epidemiology and natural history of tonsillar HPV
infections remains poorly characterized. Our aim was to characterize such
infections in the Danish population in tumor-free tonsillar tissue. Unlike
previous studies, we considered both palatine tonsils. We examined both tonsils
from 80 patients with peritonsillar abscess (n = 25) or chronic tonsillar disease
(n = 55). HPV was detected by nested PCR with PGMY 09/11 and GP5+/GP6+L1
consensus primers, and typed by sequencing. Samples were also analyzed using a
higher-throughput method, the CLART HPV 2 Clinical Array Assay. The overall
prevalence of HPV tonsillar infection was 1.25 % (1/80, 95 % CI 0.03-6.77 %) by
nested PCR, and 0 % by CLART HPV2 Clinical Array. The HPV-positive patient was a
16-year-old female with recurrent tonsillitis and tonsillar hypertrophy. The type
detected was HPV6. HPV was not detected in the contralateral tonsil of this
patient. Compared to cervical HPV infections in Denmark, tonsillar HPV infections
are 10- to 15-fold less frequent. In the HPV-positive patient in this study, HPV
was detected in only one of the tonsils. This raises the possibility that prior
studies may underestimate the prevalence of HPV infections, as they do not
consider both palatine tonsils.
PMID- 25112606
TI - Connective tissue diseases: A mechanism of B cell hyperactivity in SLE.
PMID- 25112607
TI - Metallogel template fabrication of pH-responsive copolymer nanowires loaded with
silver nanoparticles and their photocatalytic degradation of methylene blue.
AB - Poly(N,N'-methylenebisacrylamide-4-vinylpyridine) (P(MBA-4VP)) nanowires loaded
with silver nanoparticles (Ag NPs) have been fabricated by silver metallogel
template copolymerization, and subsequently, silver ions are reduced instead of
the template being removed. Ag NPs with a diameter of 5-15 nm were dispersed
throughout the core of P(MBA-4VP) nanowires. The size and distribution of the
formed Ag NPs could be finely controlled by reduction time. The pH sensitivity of
P(MBA-4VP) nanowires offers the possibility of Ag NP release from the nanowires
under acidic conditions. The photocatalytic performance of the P(MBA-4VP)
nanowires loaded with Ag NPs was evaluated for the degradation of methylene blue
(MB) under UV light irradiation. Their rate of degradation is dependent on the
content and size of the Ag NPs, as well as the pH values of the MB solution.
Moreover, the P(MBA-4VP) nanowires loaded with Ag NPs exhibited high
photostability, and the photocatalytic efficiency reduced by only 1.81% after
being used three times.
PMID- 25112608
TI - Evolution of an adenine-copper cluster to a highly porous cuboidal framework:
solution-phase ripening and gas-adsorption properties.
AB - The synthesis and directed evolution of a tetranuclear copper cluster, supported
by 8-mercapto-N9-propyladenine ligand, to a highly porous three-dimensional cubic
framework in the solid state is reported. The structure of this porous framework
was unambiguously characterized by X-ray crystallography. The framework contains
about 62 % solvent-accessible void; the presence of a free exocyclic amino group
in the porous framework facilitates reversible adsorption of gas and solvent
molecules. Oriented growth of framework in solution was also tracked by force and
scanning electron microscopy studies, leading to identification of an intriguing
ripening process, over a period of 30 days, which also revealed formation of
cuboidal aggregates in solution. The elemental composition of these cuboidal
aggregates was ascertained by EDAX analysis.
PMID- 25112604
TI - Pharmacogenetics: can genes determine treatment efficacy and safety in JIA?
AB - Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic
condition in childhood, with many children requiring immunomodulatory therapies
for many years following diagnosis. A considerable proportion of children
experience therapeutic inefficacy or substantial adverse effects, or both, but a
lack of reliable clinical indicators and biomarkers to predict treatment response
prevents optimization of existing therapies. The identification of valid
candidate gene variants involved in the pathways of methotrexate and etanercept,
the most commonly used medications in JIA, has seen little success to date. The
limited success of these studies is possibly due to the presence of confounding
variables in the study populations, the heterogeneity of outcome parameters used
to determine treatment response and the small number of candidate gene variants
analysed. The first genome-wide pharmacogenetic study in JIA has identified gene
regions of particular biological interest, but these findings require validation.
Moreover, epigenetic mechanisms as well as ontogeny processes might be additional
factors influencing drug responses. Access to large, well-documented JIA cohorts
and the rapid development of advanced genome analytics is ushering in a
personalized approach to treatment. The discovery of new pharmacogenomic
biomarkers and systems pathways can provide new drug targets and predictive tools
for improved drug response and fewer adverse drug reactions in JIA.
PMID- 25112609
TI - Efficacy and safety of dipeptidyl peptidase-4 inhibitors as an add-on to insulin
treatment in patients with Type 2 diabetes: a review.
AB - AIM: To review and discuss the results from the clinical controlled trials
comparing a dipeptidyl peptidase-4 inhibitor with placebo treatment as add-on to
insulin treatment with respect to changes in HbA1c , weight, fasting plasma
glucose, risk of hypoglycaemia and safety in patients with Type 2 diabetes.
METHODS: We searched the MEDLINE and PubMed databases to identify all randomized
controlled clinical trials evaluating dipeptidyl peptidase-4 inhibitors as an add
on to insulin in patients with Type 2 diabetes, which were selected for review.
The abstracts and posters of the recent annual meetings of the American Diabetes
Association and European Association for the Study of Diabetes were hand
searched, as were the reference lists of articles identified. RESULTS: Adding a
dipeptidyl peptidase-4 inhibitor to insulin treatment resulted in a glucose
lowering effect of ~ 6.6-8.7 mmol/mol (0.60-0.80%) from a baseline HbA1c of 67-78
mmol/mol (8.3-9.3%), without increasing the risk of hypoglycaemia. The dipeptidyl
peptidase-4 inhibitor treatment had no effect on body weight or daily dose of
insulin. The frequency and severity of adverse events did not differ between
dipeptidyl peptidase-4 inhibitor and placebo treatment. CONCLUSION: Adding a
dipeptidyl peptidase-4 inhibitor treatment to insulin has a moderate effect on
HbA1c , a weight-neutral effect and a good safety profile. The risk of
hypoglycaemia is not increased despite a significant improvement in HbA1c .
PMID- 25112610
TI - Modifications to nano- and microstructural quality and the effects on mechanical
integrity in Paget's disease of bone.
AB - Paget's disease of bone (PDB) is the second most common bone disease mostly
developing after 50 years of age at one or more localized skeletal sites; it is
associated with severely high bone turnover, bone enlargement, bowing/deformity,
cracking, and pain. Here, to specifically address the origins of the deteriorated
mechanical integrity, we use a cohort of control and PDB human biopsies to
investigate multiscale architectural and compositional modifications to the bone
structure (ie, bone quality) and relate these changes to mechanical property
measurements to provide further insight into the clinical manifestations (ie,
deformities and bowing) and fracture risk caused by PDB. Here, at the level of
the collagen and mineral (ie, nanometer-length scale), we find a 19% lower
mineral content and lower carbonate-to-phosphate ratio in PDB, which accounts for
the 14% lower stiffness and 19% lower hardness promoting plastic deformation in
pathological bone. At the microstructural scale, trabecular regions are known to
become densified, whereas cortical bone loses its characteristic parallel-aligned
osteonal pattern, which is replaced with a mosaic of lamellar and woven bone.
Although we find this loss of anisotropic alignment produces a straighter crack
path in mechanically-loaded PDB cases, cortical fracture toughness appears to be
maintained due to increased plastic deformation. Clearly, the altered quality of
the bone structure in PDB affects the mechanical integrity leading to
complications such as bowing, deformities, and stable cracks called fissure
fractures associated with this disease. Although the lower mineralization and
loss of aligned Haversian structures do produce a lower modulus tissue, which is
susceptible to deformities, our results indicate that the higher levels of
plasticity may compensate for the lost microstructural features and maintain the
resistance to crack growth.
PMID- 25112611
TI - Review of the hymenopteran fauna of New Caledonia with a checklist of species.
AB - The hymenopteran fauna of New Caledonia is reviewed and compared with that of
Australia and New Zealand, as well as other islands in the south-west Pacific. In
conclusion, several different scenarios (e.g., recent dispersal events and
radiations) can be used to explain the extant distribution of New Caledonian
Hymenoptera. A detailed checklist of 409 species and subspecies of Hymenoptera of
New Caledonia is provided, along with estimates of the undescribed fauna, and a
summary of the general biology of the families represented in the region.
PMID- 25112605
TI - Adverse reactions to biologic agents and their medical management.
AB - Biologic agents have substantially advanced the treatment of immunological
disorders, including chronic inflammatory and autoimmune diseases. However, these
drugs are often associated with adverse events (AEs), including allergic,
immunological and other unwanted reactions. AEs can affect almost any organ or
system in the body and can occur immediately, within minutes to hours, or with a
delay of several days or more after initiation of biologic therapy. Although some
AEs are a direct consequence of the functional inhibition of biologic-agent
targeted antigens, the pathogenesis of other AEs results from a drug-induced
imbalance of the immune system, intermediary factors and cofactors, a complexity
that complicates their prediction. Herein, we review the AEs associated with
biologic therapy most relevant to rheumatic and immunological diseases, and
discuss their underlying pathogenesis. We also include our recommendations for
the medical management of such AEs. Increased understanding and improved risk
management of AEs induced by biologic agents will enable better use of these
versatile immune-response modifiers.
PMID- 25112612
TI - Taxonomic revision of the ornate skink (Oligosoma ornatum; Reptilia: Scincidae)
species complex from northern New Zealand.
AB - Although the New Zealand skink fauna is known to be highly diverse, a substantial
proportion of the recognised species remain undescribed. We completed a taxonomic
revision of the ornate skink (Oligosoma ornatum (Gray, 1843)) as a previous
molecular study indicated that it represented a species complex. As part of this
work we have resolved some nomenclatural issues involving this species and a
similar species, O. aeneum (Girard, 1857). A new skink species, Oligosoma roimata
sp. nov., is described from the Poor Knights Islands, off the northeast coast of
the North Island of New Zealand. This species is diagnosed by a range of
morphological characters and genetic differentiation from O. ornatum. The
conservation status of the new taxon appears to be of concern as it is endemic to
the Poor Knights Islands and has rarely been seen over the past two decades.
PMID- 25112613
TI - Description of Mitogoniella mucuri sp. nov. (Opiliones: Gonyleptidae) and
considerations on polymorphic traits in the genus and Gonyleptidae.
AB - Mitogoniella mucuri sp. nov. is described for some caves in Minas Gerais, Brazil.
This species differs from other Mitogoniella species by large tubercles on the
ocularium that have fused bases and free apices (or almost fully fused tubercles
with bifurcated apices), and by a large dry-mark between tubercles on the
longitudinal groove of area III. Mitogoniella species are hard to recognize:
their males lack any armature on leg IV (normally an important diagnostic
character among gonyleptid species), and they also present many polymorphisms in
coloration (dry-mark), male secondary sex characters, the number of dorsal scutal
granules, and the shapes of tubercles on the ocularium. The patterns of these
polymorphisms are discussed for the genus and for the family. The present work
also presents new occurrences for all the species of the genus, and their
biogeography is discussed.
PMID- 25112614
TI - A new species of the genus Pethia from Mizoram, northeastern India (Teleostei:
Cyprinidae).
AB - The paper describes Pethia expletiforis, a new cyprinid species from the Ka-ao
River, Kaladan drainage, Mizoram, India. It is distinguished from its congeners
in the Chindwin-Irrawaddy and Ganga-Brahmaputra drainages by the combination of:
a complete lateral line, nine predorsal scales, 12 circumpeduncular scales,
1/24/1/31/2 transverse scales, a black blotch on the caudal peduncle, and the
absence of a humeral mark and barbels.
PMID- 25112615
TI - A new species of Hemiphyllodactylus (Reptilia: Gekkonidae) from northern Vietnam.
AB - We describe a new species of the genus Hemiphyllodactylus on the basis of four
specimens from Cao Bang Province, northern Vietnam. Hemiphyllodactylus zugi sp.
nov. is distinguished from the remaining congeners by a combination of the
following characters: a bisexual taxon; average SVL of adult males 41 mm, of
adult female 46.6 mm; chin scales bordering mental and first infralabial
distinctly enlarged; digital lamellae formulae 3-4-4-4 (forefoot) and 4-5-5-5
(hindfoot); femoral and precloacal pore series continuous, 18-21 in total in
males, absent in female; cloacal spur single in males; dorsal trunk pattern of
dark brown irregular transverse bands; dark lateral head stripe indistinct; upper
zone of flank with a series of large light spots, edged above and below in dark
grey; caecum and gonadal ducts unpigmented.
PMID- 25112616
TI - Schillerosaurus gen. nov., a replacement name for the lizard genus Schilleria
Evans and Chure, 1999 a junior homonym of Schilleria Dahl, 1907.
PMID- 25112617
TI - Names and publication dates of the Brachyura in F.E. Guerin (Guerin-Meneville)
(Crustacea: Decapoda).
AB - The names and dates of the publications of Brachyura of Guerin (Guerin-Meneville
from 1836) are reviewed, and previously unidentified or overlooked names are
identified. Several identical new names used in multiple publications by Guerin
(also under the name Guerin-Meneville), and others that appeared in the same year
necessitated the accurate determination of publication dates to establish
priority. The authorships of three names should be credited to Guerin (1832):
Gecarcinus lateralis (Gecarcinidae), Halimus aries (Majidae), and Libinia spinosa
(Epialtidae), the first previously attributed to Freminville (1835), the last two
to H. Milne Edwards (1834). The overlooked genus- and species-group names
Cyclocarcinus pinnotheroides Guerin-Meneville, 1838, are determined to be senior
subjective synonyms of the genus- and species-group names Hapalonotus reticulatus
(De Man, 1879) (Pilumnidae). Applying Article 23.9.1 of the International Code of
Zoological Nomenclature, precedence is reversed between the genus-group names and
the correct name is Hapalonotus pinnotheroides (Guerin-Meneville, 1838). Current
and widespread use of the genus-group name Thalamita Latreille, 1829 (31 March)
(Portunidae) is threatened by the overlooked Thalamites Guerin, 1829 (21 March),
and the precedence of the names is also reversed to maintain usage of the former.
The genus-group name Eurypodius Guerin (Inachidae) is shown to have been
established in 1828, not 1825. Included is a complete bibliography of the
publications in which Guerin (also under Guerin-Meneville) established new names
for Brachyura, with their accurate publication dates.
PMID- 25112619
TI - New records and distribution modeling of Gryne orensis (Sorensen) (Opiliones:
Cosmetidae) support the Mesopotamian-Yungas disjunction in subtropical Argentina.
AB - The presence of Gryne orensis (Sorensen) (Opiliones: Cosmetidae) in a Yungas
locality (northwestern Argentina) is reported for the first time, providing new
evidence for the Mesopotamian-Yungas disjunct pattern. Combining a total of 19
new Mesopotamian records with previous, reliable citations from the literature, a
dataset of 45 points was used to model the potential distribution of the species,
using the presence-only methods BIOCLIM and MAXENT. Models supported the
existence of a distributional gap across the Semiarid Chaco. The imprecise
literature record from "El Impenetrable", province of Chaco, is assigned to three
tentative locations to evaluate if models are affected by their inclusion; in all
cases, the disjunction was maintained. It was thereby estimated that the actual
record might have originated in a site closer to the Humid Chaco and/or
associated to streams. This paper also provides a statement of the bioclimatic
profile and identification of major environmental constraints that define the
range of G. orensis.
PMID- 25112618
TI - Three new species of Macrelmis Motschulsky, 1859 (Coleoptera: Elmidae: Elminae)
from the Brazilian Cerrado Biome with updated key for the Macrelmis of Brazil.
AB - Three new species of Macrelmis Motschulsky, 1859 (Macrelmis bispo sp. nov.,
Macrelmis froehlichi sp. nov., and Macrelmis nessimiani sp. nov.) are herein
described and illustrated. The species were collected from several streams in
Goias State, Brazil, a formerly unknown region concerning Elmidae fauna. We also
provide an updated key for the Macrelmis species of Brazil.
PMID- 25112620
TI - Latitudinal patterns in the diversity of two subgenera of the genus Daphnia O.F.
Muller (Crustacea: Cladocera: Daphniidae).
AB - Daphnia O.F. Muller (Crustacea: Cladocera: Daphniidae) is an important model in
biology. It was concluded earlier that subgenus Daphnia s.str. occurs mainly in
the northern hemisphere, subgenus Daphnia (Ctenodaphnia) in the southern
hemisphere, which could suggest that: (1) the subgeneric differentiation is
correlated with the Laurasia-Gondwanaland subdivision and (2) D. (Ctenodaphnia)
is a taxon of Gondwanian origin. Some authors even discussed mechanisms of
maintaince of the "ancient subgeneric north-south split", regarding such a
pattern as paradoxical. But both molecular clock calculations and fossils of both
subgenera from the Jurassic/Cretaceous boundary of Mongolia compromise such ideas
and suggest an earlier, Pangaean, differentiation of the subgenera. We discuss
the distribution of Daphnia worldwide based on recent literature. Our analysis
covers literature data on all described and on undescribed taxa revealed by
genetical methods. Distributional data were associated with five main zones:
southern cold (I), southern temperate (II), tropical (III), northern temperate
(IV), and northern cold (V) zone. We found no "subgeneric north-south split": the
distribution of Daphnia s.str. is dissymmetric between the hemispheres
(antipolar), while that of Ctenodaphnia is sub-symmetric (bipolar). We suggest
that both patterns are not of Mesozoic, but of Cenozoic origin. Mesozoic
differentiation of the subgenera does not contradict a recent origin of the
extant species, as found in e.g. Notostraca. A superficially attractive
hypothesis about a Gondwanian origin of a taxon (Daphnia (Ctenodaphnia))
therefore did not pass the test of the fossil records. In addition, we agree with
the opinion that an antipolar is only a variant of a bipolar pattern, as a result
of an extinction in the southern hemisphere, and that these patterns are mid-late
Cenozoic instead of Mesozoic.
PMID- 25112621
TI - A new cave-dwelling millipede of the genus Scutogona from central Portugal
(Diplopoda, Chordeumatida, Chamaesomatidae).
AB - A new cave-dwelling species of the genus Scutogona Ribuat, 1913, S. minor n. sp.,
is described from caves of Sico karst in central Portugal. The classification and
delimitation of Scutogona vis-a-vis related genera, in particular Meinerteuma
Mauries, 1982, is discussed.
PMID- 25112622
TI - Diversity of Aulacidae (Hymenoptera: Evanioidea) in the oceanic Ogasawara Islands
(Japan), with description of a new species from Anijima Island.
AB - In the context of the biodiversity conservation of the oceanic Ogasawara Islands,
the parasitoid species of Aulacidae are reviewed. We examined material from eight
islands with or without invasion of the introduced lizard Anolis carolinensis
(Voigt 1832) (green anoles): two species of Pristaulacus Kieffer 1900, P.
boninensis Konishi, 1989, and P. anijimensis sp. nov., are recognized. The former
species is widely distributed in the islands, whereas the latter species is found
from a single island only, Anijima Island. Although this island appears to be
currently well preserved, the recent introduction of green anoles will probably
affect the conservation status of many species, including the endemic P.
anijimensis sp. nov. A description of the new species, detailed drawings and
descriptions of genitalia of both recognized species, an updated key to Japanese
Aulacidae, and a brief discussion on the conservation aspects of Aulacidae in the
Ogasawara Islands are provided.
PMID- 25112623
TI - A new species of Lakshmia Yakovlev, 2004 (Lepidoptera: Cossidae) from Northern
Thailand with a world catalogue of the genus.
PMID- 25112624
TI - Gerromorpha (Hemiptera: Heteroptera) of eastern Mato Grosso State, Brazil:
checklist, new records, and species distribution modeling.
AB - The infraorder Gerromorpha comprises semiaquatic bugs, most of which spend much
of their lifetime on the water surface, between floating plants, or on the
margins of water bodies. Based on literature and collections made on streams and
lakes on municipalities of eastern Mato Grosso, Brazil, a list has been
elaborated with 52 species, including several new records. Out of the recorded
species, 26 belong to the family Veliidae, 20 to Gerridae, three to
Hydrometridae, two to Mesoveliidae, and one to Hebridae. The modeling of the
potential geographical distribution is also presented for the 20 species that
have been recorded for the first time from the state.
PMID- 25112625
TI - A new species of Physoschistura (Pisces: Nemacheilidae) from northern Thailand.
AB - Physoschistura chulabhornae, new species, is described from Maechaem River, a
tributary of Ping River, upper Chaophraya River drainage, Chiangmai province,
Thailand. It is distinguished from all other known species of Physoschistura in
having an incomplete lateral line reaching at least to the origin of the anal fin
with 62-83 lateral-line canal pores, the dorsal-fin origin slightly in front of
the pelvic-fin origin, no axillary pelvic lobe, and a suborbital flap in the
shape of a hammer head in the male.
PMID- 25112626
TI - A new species in the genus Pseudorhyncomyia Peris, 1952 and the identity of P.
deserticola Zumpt and Argo, 1978 (Diptera, Rhiniidae).
AB - The genus Pseudorhyncomyia Peris, 1952 is re-described and shown to have two
valid species: P. braunsi (Villeneuve, 1920) and P. aethiopica sp. nov. The
latter is described on the basis of a single male specimen captured near Ado,
Ethiopia, in 1953. Nominal species P. deserticola Zumpt and Argo, 1978 is
transferred to Zumba Peris, 1951, where it is placed as a junior synonym of Z.
antennalis (Villeneuve, 1929), syn. nov.
PMID- 25112627
TI - The Pselaphinae of Madagascar. II. Redescription of the genus Semiclaviger
Wasmann, 1893 (Coleoptera: Staphylinidae: Pselaphinae: Clavigeritae) and synonymy
of the subtribe Radamina Jeannel, 1954.
AB - The enigmatic Madagascan genus Semiclaviger Wasmann is among the most
morphologically distinct members of the obligately myrmecophilous pselaphine
supertribe Clavigeritae. Here, the genus is redescribed, and the lectotype of the
type species S. sikorae Wasmann is designated. We present a detailed study of the
morphology of Semiclaviger, which supports its uniqueness among the Clavigeritae.
The systematic position of the genus, and the validity of its subtribe Radamina,
are discussed leading us to place Radamina in synonymy with Clavigerodina.
PMID- 25112629
TI - New species of Narnia (Hemiptera: Heteroptera: Coreidae: Coreinae: Anisoscelini)
from Mexico and key to the known species of the genus.
AB - One new species of Narnia is described from Mexico, N. anaticula sp. nov. A key
to the species is provided together with dorsal view photograph of each known
species of Narnia. The genus is divided in two groups according the color of the
dorsal abdominal segments.
PMID- 25112628
TI - Working and reference check list for fireflies of Melanesia (Coleoptera:
Lampyridae: Luciolinae).
AB - Twenty-three species of Lampyridae (fifteen of them new) collected during the
1969-70 Alpha Helix scientific expedition to New Guinea are now characterized by
both behavioural and taxonomic data. For ease of identification, relocation of
specimens, and location of all pertinent literature this check list is presented.
PMID- 25112630
TI - Redescription of Parapercis punctata (Cuvier, 1829) and status of Neosillago
Castelnau, 1875 and its type species Neosillago marmorata Castelnau, 1875
(Perciformes: Pinguipedidae).
AB - The status of two doubtful fish species is reviewed. Percis punctata Cuvier, 1829
is confirmed to be a valid species of Parapercis Bleeker, 1863 and a senior
synonym of Parapercis guezei Fourmanoir, 1966. A redescription of Parapercis
punctata is provided, based on four specimens collected from the western Indian
Ocean. Examination of the holotype of Neosillago marmorata Castelnau, 1875
revealed that Neosillago is a junior synonym of Parapercis and N. marmorata is a
junior synonym of Parapercis nebulosa (Quoy & Gaimard, 1825).
PMID- 25112632
TI - Revision of the genus Ateralphus Restello, Iannuzzi & Marinoni, 2001 (Coleoptera:
Cerambycidae: Lamiinae).
AB - A revision of the genus Ateralphus Restello, Iannuzzi & Marinoni, 2001, based on
the detailed study of the morphology of the type-species and on the external
morphology and terminalia of the others species is presented. The genus and
species are redescribed and three new species are described. The genus is
composed of nine species: A. dejeani (Lane, 1973), A. javariensis (Lane, 1965),
A. lacteus Galileo & Martins, 2006, A. senilis (Bates, 1862), A. subsellatus
(White, 1855), A. variegatus (Mendes, 1938), A. auritarsus new species, A.
lucianeae new species and A. tumidus new species. A key for identification of the
species and maps of their geographical distribution are provided.
PMID- 25112633
TI - The genus Yemmalysus Stusak (Hemiptera: Heteroptera: Berytidae) from China.
AB - Species of the genus Yemmalysus Stusak, 1972 from China are treated in this
paper: Y. parallelus Stusak, 1972 and Y. brevispinus Cai, Ye & Bu, sp. nov.
Scanning electron micrographs of the head, thorax, external scent efferent system
and scutellar spine, illustrations of the male genital capsules and parameres of
the two species, and a key to the species of this genus are provided to assist in
identification. Type specimens of Y. brevispinus sp. nov. are deposited in
Institute of Entomology, College of Life Sciences, Nankai University, Tianjin,
China.
PMID- 25112634
TI - Description of three species of Halmyrapseudes (Crustacea: Tanaidacea:
Parapseudidae), with a discussion of biogeography.
AB - We describe Halmyrapseudes gutui sp. nov. from a mangrove area on Lidee Island,
southern Thailand. This species closely resembles H. cooperi, H. killaiyensis,
and H. thaumastocheles, but differs in having the lacinia mobilis with three
teeth, and the pereopod 1 carpus with 0,1 or 1,1 ventral simple setae proximal to
each spiniform seta. We redescribed and synonymized two species of questionable
affiliation, Apseudes cooperi and A. digitalis, placing them in Halmyrapseudes,
and partly redescribed Halmyrapseudes killaiyensis. Halmyrapseudes and
Pseudohalmyrapseudes have disjunct distributions. Halmyrapseudes is similar in
distribution to two freshwater fish taxa whose distributions are considered to
reflect the breakup of Gondwana and subsequent continental drift.
Pseudohalmyrapseudes occurs around Australia, and its distribution seems to be
separated from that of Halmyrapseudes by Wallace's Line or Huxley's Line, which
are distributional barriers for both terrestrial organisms and an amphidromous
shrimp. The adjacent distributions and morphological similarities suggest that
Halmyrapseudes and Pseudohalmyrapseudes are sister taxa.
PMID- 25112635
TI - Revision of the Neotropical genus Malacophagomyia (Diptera: Sarcophagidae) with
description of a new species.
AB - The small Neotropical genus Malacophagomyia Lopes is revised. Two previously
recorded species from tropical South America are redescribed: M. filamenta
(Dodge) and M. kesselringi Kano & Lopes. One new species is described, M.
rivadavia sp. nov., from temperate southern South America. The structures of the
male genitalia of the species of this genus are compared, and some female
genitalic structures of M. filamenta are reinterpreted. Diagnostic characters to
recognize the three species are given. Additionally, a key to described species
of Malacophagomyia is presented.
PMID- 25112636
TI - Two new genera and species of Tingidae from Cretaceous amber from Myanmar (Burma)
(Hemiptera: Heteroptera).
AB - From the Upper Cretaceous Burmese amber, the first known genera of Tingidae,
Spinitingis n. gen. and Burmacader n. gen. with the species Spinitingis
ellenbergeri n. sp. and Burmacader multivenosus n. sp., are described and
figured. Their systematic placement and relationship to fossil and extant taxa
are discussed.
PMID- 25112637
TI - A new genus of Saucrosmylinae (Insecta, Neuroptera) from the Middle Jurassic of
Daohugou, Inner Mongolia, China.
AB - A new genus and new species of Saucrosmylinae (Insecta, Neuroptera) is described
as Huiyingosmylus bellus gen. et sp. nov., based on a well-preserved forewing
from the Middle Jurassic of Daohugou, Inner Mongolia, China. Huiyingosmylus gen.
nov. is characterized by the large size of forewing, relatively wide R1 space
with several rows of cells, anteriorly bent Rs, dense crossveins over the entire
wing and undulate outer margin. A key to the genera of Saucrosymylinae is
provided.
PMID- 25112638
TI - Two new species of Lachesilla in the andra group, from the Chapada Diamantina,
Bahia, Brazil (Psocodea: 'Psocoptera': Lachesillidae).
AB - Two new species of Lachesilla in the andra group are described from Brazil, where
the group was previously unknown. They raise to five the number of species in the
group known in South America. An identification key for females of the andra
group in South America is included.
PMID- 25112639
TI - Two new species of Hemielimaea Brunner von Wattenwyl from China.
AB - Two new species Hemielimaea (Hemielimaea) paracari sp. nov. and H. (H.) parva sp.
nov. from southwestern China are described. Characteristics of the stridulatory
file on underside of male left tegmen, male stridulatory area on left and right
tegmen, and abdominal apex of male are provided. Important and necessary
illustrations of the new species are presented. Materials come from the following
two depositories: Institute of Zoology, Chinese Academy of Sciences, Beijing,
China (IZCAS), and China Agricultural University, Beijing, China (CAU).
PMID- 25112640
TI - Revision of the Empis subgenus Enoplempis Bigot, east of the Rocky Mountains
(Diptera: Empididae).
AB - The Empis subgenus Enoplempis Bigot, east of the Rocky Mountains of North America
is revised. A total of 19 species are recorded from this region including seven
new species: E. (En.) amytis Walker, E. (En.) appalachicola Sinclair sp. nov., E.
(En.) arthritica Melander, E. (En.) ctenonema Melander, E. (En.) enodis Melander,
E. (En.) gladiator Melander, E. (En.) gulosa Coquillett, E. (En.) loripedis
Coquillett, E. (En.) montywoodi Brooks sp. nov., E. (En.) nodipoplitea Steyskal,
E. (En.) nuda Loew, E. (En.) pectinata Sinclair sp. nov., E. (En.) penicillata
Brooks sp. nov., E. (En.) prodigiosa Cumming sp. nov., E. (En.) snoddyi Steyskal,
E. (En.) stenoptera Loew, E. (En.) tridentata Coquillett, E. (En.) vockerothi
Cumming sp. nov., E. (En.) volsella Sinclair sp. nov. The following new
synonymies are designated: E. (En.) longipes Loew, E. (En.) longeoblita Steyskal,
E. (En.) deterra Walley = E. (En.) amytis; E. (En.) cacuminifer Melander = E.
(En.) gulosa. Lectotypes are designated for the following species: E. (En.)
arthritica, E. (En.) cacuminifer, E. (En.) ctenonema, E. (En.) enodis, E. (En.)
gladiator, E. (En.) loripedis, E. (En.) stenoptera and E. (En.) tridentata. A key
to eastern species is presented and distributions illustrated. The form of
nuptial gift presentation displayed within this group, including the use of
balloons (with or without prey) and unwrapped prey are indicated for species when
known.
PMID- 25112641
TI - Redefinition of the genus Silphitrombium (Trombidiformes: Neothrombiidae) with
description of two new species parasitizing beetles (Coleoptera: Elateridae,
Tenebrionidae) from Iran.
AB - Two new species of Silphitrombium Fain, 1992 (Acari: Prostigmata:
Neothrombiidae), ectoparasites of beetles (Insecta: Coleoptera), are described
from Sistan and Baluchestan Province, eastern Iran: S. elateridum sp. nov. on
Heteroderes heideni Reitter, 1891 (Col.: Elateridae) and S. iranicum sp. nov. on
Opatroides punctulatus Brulle, 1832 (Col.: Tenebrionidae) and the genus
Silphitrombium is redefined. It is the first record of the relationship between
beetles of the families Elateridae and Tenebrionidae, and mites of the genus
Silphitrombium. A key to the species of the genus is presented.
PMID- 25112642
TI - Four new species of Acoela from Chile.
AB - Acoels are with few exceptions marine worms and a common component of the
interstitial meiofauna. In this study we present new species to science belonging
to Isodiametridae and Solenofilomorphidae. The new species, Isodiametra finkei n.
sp., Postaphanostoma nilssoni n. sp., Pseudaphanostoma hyalinorhabdoida n. sp.
and Solenofilomorpha pellucida n. sp. were all collected in Chile during March
2012. Nucleotide sequences for the ribosomal genes 18S rDNA and 28S rDNA as well
as COI mtDNA have been determined for the new species and used in a maximum
likelihood analysis to further support their classification.
PMID- 25112643
TI - Morphology of a neglected large-sized species of Geophilus from Iran (Chilopoda:
Geophilidae).
AB - Geophilus gigas was described briefly by Attems in 1951 from two sites in Iran,
but neither reported nor cited subsequently. The original description is
inadequate to understand the full morphology and the taxonomic position of the
species. Thus it is here redescribed and figured in detail based on the
examination of a syntype and newly collected specimens. Furthermore it is
compared with the most similar species of the genus Geophilus. G. gigas can be
reliably distinguished from other related species for the maximum body size (more
than 6 cm), the arrangement and extent of the sternal pore-fields (with
additional groups of pores), the coxal pores number and distribution (tens,
scattered), and the size of the ultimate legs (swollen in both sexes).
PMID- 25112644
TI - Review of the largest species group of the New World seed beetle genus Sennius
Bridwell (Coleoptera: Chrysomelidae), with host plant associations.
AB - Sennius Bridwell is a New World genus of Bruchinae. Most species are placed in
eight groups. In this study the species of the S. abbreviatus group are reviewed
based on characters of the external morphology and the male genitalia. The group
includes 14 species, two of which are new: Sennius abbreviatus (Say, 1824), S.
bondari (Pic, 1929), S. durangensis Johnson & Kingsolver, 1973, S. lawrencei
Johnson, 1977, S. lebasi (Fahraeus, 1839), S. leucostauros Johnson & Kingsolver,
1973, S. lojaensis (Pic, 1933), S. medialis (Sharp, 1885), S. nappi Ribeiro-Costa
& Reynaud, 1998, S. rufomaculatus (Motschulsky, 1874), S. transversesignatus
(Fahraeus, 1839), S. trinotaticollis (Pic, 1930), S. vivi sp. nov. and S. flinte
sp. nov. The S. abbreviatus group differs from other groups by the pattern of
sclerites and the shape of the internal sac of the male genitalia, and has three
subgroups, defined here. The lectotype of S. lebasi is designated. New host plant
records are presented for S. lojaensis and S. transversesignatus, and new
distribution records for S. lawrencei, S. lojaensis and S. trinotaticollis.
PMID- 25112645
TI - Review of the genus Cystocnemis (Coleoptera: Chrysomelidae: Chrysomelinae) with
descriptions of two new species .
AB - Two new species of Cystocnemis (s. str.) Motschulsky, 1860 namely C. levmedvedevi
sp. nov. and C. zintshenkoi sp. nov. are described from the Mongolian Altai
(Mongolia, Hovd aimag) and Southern Altai (Kazakhstan, East-Kazakhstan region)
respectively. Generic diagnosis as well as key to species and subspecies of
Cystocnemis are provided. Zoogeographical affinities of Entomoscelini are
discussed.
PMID- 25112646
TI - Five new eyed species of Sinella (Collembola: Entomobryidae) from China, with a
key to the eyed species of the genus.
AB - Five new eyed species of Sinella from China, respectively with 3, 3, 2, 1, 1
ommatidia on each side, are described here: S. longisensilla sp. nov., S. yui sp.
nov., S. pseudobrowni sp. nov., S. sacellum sp. nov. and S. gracilis sp. nov.
Clypeal chaetae and chaetae along cephalic groove exhibit differences among these
species and could be used to distinguish species in Sinella and Coecobrya. A key
to the eyed species of the genus is given.
PMID- 25112647
TI - Non-biting midges of the tribe Tanytarsini in Eocene amber from the Rovno region
(Ukraine): a pioneer systematic study with notes on the phylogeny (Diptera:
Chironomidae).
AB - The first detailed systematic study on the tanytarsine chironomids recorded in
the Eocene amber from the Rovno region (Ukraine) revealed seven new taxa.
Archistempellina gen. nov., represented by A. bifurca sp. nov. (type for the
genus, male) and A. falcifera sp. nov. (male), displays characters similar to
those found in Stempellina Thienemann et Bause, and is recognized as one of
probable basal lineages in the subtribe Stempellinina Shilova. Corneliola gen.
nov., represented by C. avia sp. nov. (male, female), combines features known
from several genera of the tribe Tanytarsini, and tentatively is regarded as the
closest relative of Constempellina Brundin. Rheotanytarsus alliciens sp. nov.
(male), featuring a long hypopygial digitus, is considered to be the oldest
species of the genus. Tanytarsus congregabilis sp. nov. (male) is the first known
Eocene representative of the lugens systematic species group. A complemented
description of the male of Tanytarsus serafini Gilka is provided as well.
PMID- 25112648
TI - The mammal type specimens at the Natural History Museum, University of Oslo,
Norway.
AB - A catalog of mammalian type specimens in the collections of Natural History
Museum, University of Oslo, Norway, is presented. All type specimens in the
Museum's mammal collection were revisited and the respective label information
was compared with the data provided in the original descriptions. Most taxa were
described from type series with no specimen particularly assigned to holotype.
The compiled catalog of the type specimens is not intended as a taxonomic
revision of the respective taxa, which is why we have not designated lectotypes
from the collection's type series. Specimens that were clearly marked as "the
type" in the original description were considered holotypes. The catalog consists
of 19 taxa, with the year of authority corrected for three taxa.
PMID- 25112649
TI - A new Odontothrips species (Thysanoptera: Thripidae) from Iran .
PMID- 25112650
TI - Testing departure from additivity in Tukey's model using shrinkage: application
to a longitudinal setting.
AB - While there has been extensive research developing gene-environment interaction
(GEI) methods in case-control studies, little attention has been given to sparse
and efficient modeling of GEI in longitudinal studies. In a two-way table for GEI
with rows and columns as categorical variables, a conventional saturated
interaction model involves estimation of a specific parameter for each cell, with
constraints ensuring identifiability. The estimates are unbiased but are
potentially inefficient because the number of parameters to be estimated can grow
quickly with increasing categories of row/column factors. On the other hand,
Tukey's one-degree-of-freedom model for non-additivity treats the interaction
term as a scaled product of row and column main effects. Because of the
parsimonious form of interaction, the interaction estimate leads to enhanced
efficiency, and the corresponding test could lead to increased power.
Unfortunately, Tukey's model gives biased estimates and low power if the model is
misspecified. When screening multiple GEIs where each genetic and environmental
marker may exhibit a distinct interaction pattern, a robust estimator for
interaction is important for GEI detection. We propose a shrinkage estimator for
interaction effects that combines estimates from both Tukey's and saturated
interaction models and use the corresponding Wald test for testing interaction in
a longitudinal setting. The proposed estimator is robust to misspecification of
interaction structure. We illustrate the proposed methods using two longitudinal
studies-the Normative Aging Study and the Multi-ethnic Study of Atherosclerosis.
PMID- 25112651
TI - Total versus unicompartmental knee replacement for isolated lateral
osteoarthritis: a matched-pairs study.
AB - PURPOSE: The aim of this study was to compare the functional outcome of patients
following unicompartmental knee replacement (UKR) using the Oxford domed lateral
UKR to patients who underwent cruciate-retaining total knee replacement (TKR) for
isolated osteoarthritis in the lateral compartment. METHODS: With the help of our
institutional database, we retrospectively identified 22 matched pairs with
regards to age, gender and body mass index (BMI). Functional outcome was measured
using the Oxford Knee Score (OKS) and range of motion (ROM). Complications and
revisions were recorded. RESULTS: The mean follow-up was 22 (UKR) and 19 (TKR)
months, respectively. Patients following UKR had a statistically significant
higher mean postoperative OKS and ROM: mean OKS was 43 [standard deviation (SD)
4] for UKR and 37 (SD 9) for TKR, respectively (p = 0.023); ROM was 127 degrees
(SD 13) for UKR and 107 degrees (SD 17) for TKR (p < 0.001). Additionally the
change in score was statistically significant higher in patients following UKR in
the OKS (14.3 (SD 6) vs. 9.6 (SD 8)) and in the range of motion (+12 degrees (SD
19) vs. -3 degrees (SD 20)), (p = 0.041 and p = 0.01 respectively). Survival at
two years using revision for any reason as the endpoint was 96% [95% confidence
interval (CI) 72-99] for UKR and 100% for TKR (Log-rank test, p = 0.317).
CONCLUSION: The functional results of mobile-bearing UKR for isolated
osteoarthritis in the lateral compartment compare favourably to those after
cruciate-retaining TKR in the short term. To compare survival and complications
after both procedures, longer-term follow-up is necessary.
PMID- 25112652
TI - Synthesis of nitrogen-doped zigzag-edge peripheries: dibenzo-9a-azaphenalene as
repeating unit.
AB - A bottom-up approach toward stable and monodisperse segments of graphenes with a
nitrogen-doped zigzag edge is introduced. Exemplified by the so far unprecedented
dibenzo-9a-azaphenalene (DBAPhen) as the core unit, a versatile synthetic concept
is introduced that leads to nitrogen-doped zigzag nanographenes and graphene
nanoribbons.
PMID- 25112654
TI - Attitude of physiotherapy students in Nigeria toward persons with disability.
AB - BACKGROUND: Attitudes of students of health care professions, such as
physiotherapy, toward persons with disability may influence their attitude and
practice post-qualification. OBJECTIVE: To examine attitudes toward persons with
disability among undergraduate physiotherapy students in Universities in Nigeria.
METHODS: The 30-item Attitudes toward Disabled Persons--Form A (ATDP-A) scale was
used to assess the attitudes of penultimate and final year physiotherapy students
in 3 Nigerian universities. Overall and item-by-item analyzes of responses to the
ATDP-A scale were carried out. Differences in attitude by sex, age, year and
university of study were also examined using independent t-test and one-way
ANOVA. RESULTS: One hundred and sixty-nine students with a male majority (56.2%)
participated in the study. Mean score on the ATDP-A was 94.95 +/- 17.50 with more
students (60.4%) having a score >90 which depicts positive attitude. Item-by-item
analysis of responses to the 30 items on the ATDP-A showed that negative
attitudes were preponderant on items relating to the emotional component of the
personality of persons with disability. Only age of students and their university
of study however resulted in statistically significant differences in attitudes
and older students reported better attitudes toward persons with disability.
CONCLUSIONS: Although the overall attitude of the physiotherapy students was
positive, negative stereotypes and discriminatory tendencies were observed in
issues relating to the perceived emotional capacity of persons with disabilities.
Educational strategies capable of effecting more positive attitudes in
physiotherapy students in Nigeria toward persons with disability are urgently
needed.
PMID- 25112655
TI - Severe muscle depletion predicts postoperative length of stay but is not
associated with survival after liver transplantation.
PMID- 25112653
TI - Emergency department provider preferences related to clinical practice guidelines
for tobacco cessation: a multicenter survey.
AB - OBJECTIVES: The objective was to assess current emergency department (ED)
provider practices and preferences for tobacco cessation interventions. The ED is
an opportune place to initiate smoking cessation interventions. However, little
is known about ED provider current practices and preferences for cessation
counseling in the ED. METHODS: This was a survey of ED providers conducted in
2008-2009 (including physicians, nurse practitioners, physician assistants, and
nurses), working at least half-time at 10 U.S. academic EDs, regarding adherence
to clinical practice guidelines ("5 As") and preferences for cessation
interventions/styles. Data analysis occurred in 2012-2013. RESULTS: The response
rate was 64% (800 out of 1,246 completed surveys). Providers reported strongest
adherence to asking about patient smoking status, followed by advising, with
significant variance by clinical role. Assessing, assisting, and arranging
support for patients was low overall. Most frequently used interventions were to
provide patients with a list of telephone numbers for stop-smoking counseling
(87%), pamphlets on smoking health risks and the benefits of stopping (85%), and
referrals to the National Toll-Free Smoker's Quitline (84%). Most providers (80%)
were supportive of personally conducting brief (less than 3 minutes) smoking
cessation counseling sessions during the ED visit, emphasizing education and
encouragement. The least appealing intervention was writing a prescription for
nicotine replacement therapies or medications to stop smoking (35%). CONCLUSIONS:
Interventions most likely to be used were brief and delivered with a positive
tone and included referral to external resources. The logical next step is to
design and test interventions that ED providers find acceptable.
PMID- 25112656
TI - Geriatric emergency department innovations: preliminary data for the geriatric
nurse liaison model.
AB - Older adults account for a large and growing segment of the emergency department
(ED) population. They are often admitted to the hospital for nonurgent conditions
such as dementia, impaired functional status, and gait instability. The aims of
this geriatric ED innovations (GEDI) project were to develop GEDI nurse liaisons
by training ED nurses in geriatric assessment and care coordination skills,
describe characteristics of patients that these GEDI nurse liaisons see, and
measure the admission rate of these patients. Four ED nurses participated in the
GEDI training program, which consisted of 82 hours of clinical rotations in
geriatrics and palliative medicine, 82 hours of didactics, and a pilot phase for
refinement of the GEDI consultation process. Individuals were eligible for GEDI
consultation if they had an Identification of Seniors At Risk (ISAR) score
greater than 2 or at ED clinician request. GEDI consultation was available Monday
through Friday from 9:00 a.m. to 8:00 p.m. An extensive database was set up to
collect clinical outcomes data for all older adults in the ED before and after
GEDI implementation. The liaisons underwent training from January through March
2013. From April through August 2013, 408 GEDI consultations were performed in
7,213 total older adults in the ED (5.7%, 95% confidence interval (CI) = 5.2
6.2%), 2,124 of whom were eligible for GEDI consultation (19.2%, 95% CI = 17.6
20.9%); 34.6% (95% CI = 30.1-39.3%) received social work consultation, 43.9% (95%
CI = 39.1-48.7) received pharmacy consultation, and more than 90% received
telephone follow-up. The admission rate for GEDI patients was 44.9% (95% CI =
40.1-49.7), compared with 60.0% (95% CI = 58.8-61.2) non-GEDI. ED nurses
undergoing a 3-month training program can develop geriatric-specific assessment
skills. Implementation of these skills in the ED may be associated with fewer
admissions of older adults.
PMID- 25112657
TI - New advances in the treatment of atrial fibrillation: focus on stroke prevention.
AB - INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia and brings
about significant mortality and morbidity as a result of heart failure and
ischemic stroke. Besides vitamin K antagonists (VKA), several new pharmacological
agents (nonvitamin K antagonist oral anticoagulants [NOACs]) and procedures have
since been developed to improve stroke prevention efforts in AF. AREAS COVERED:
This paper will discuss the antiplatelet agents, VKA and NOACs, and their
efficacy and safety for stroke prevention in AF. Focus will be placed on the
NOACs, their limitations and special considerations. A short assessment of other
nonpharmacological antithrombotic procedures will also be made. An extensive
PubMed search was used to identify suitable papers. EXPERT OPINION: Despite the
advent of NOACs, the VKAs will remain as an important oral anticoagulant due to
its versatility. However, convenience and limited food or drug interactions will
make NOACs attractive options. The choice between various NOACs will depend on
several important factors as illustrated below. Over time, the role for
antiplatelet agents will gradually diminish. Left atrial appendage occlusion
devices have shown promising results and may have the potential to change the way
clinicians manage thromboembolism risks related to AF.
PMID- 25112658
TI - Reirradiation as part of a salvage treatment approach for progressive non-pontine
pediatric high-grade gliomas: preliminary experiences from the German HIT-HGG
study group.
AB - BACKGROUND AND PURPOSE: The aim of the present analysis was to assess the
feasibility, toxicity, and the tumor control of reirradiation as a salvage
treatment for progressive pediatric non-pontine high-grade gliomas (HGG).
PATIENTS AND METHODS: The database of the Reference Center for Radiation Oncology
of the German HIT (HIT = German acronym for brain tumor) treatment network for
childhood brain tumors was screened for children who were reirradiated for
progressive non-pontine HGG. RESULTS: We identified eight patients (WHO grade
III: n = 5; WHO grade IV: n = 3) who underwent reirradiation between April 2006
and July 2012. Median age was 13.5 years at primary diagnosis and 14.8 years at
first progression. All patients initially underwent surgery (incomplete
resection, n = 7; biopsy, n = 1) followed by radiochemotherapy. Relapses occurred
inside (n = 2), at the margin (n = 4), and outside of the preirradiated area (n =
2). In all patients, reirradiation was tolerated well without significant acute
toxicity. Temporary clinical improvement and tumor regression on magnetic
resonance imaging (MRI) following reirradiation was reported (n = 3). However,
all patients finally died by disease progression. Median survival time was 26.2
months from initial diagnosis and 11.4 months after first progression. Median
time interval between initial radiotherapy and first reirradiation was 9.0
months. In six patients, all macroscopic tumor deposits were reirradiated. In
these patients, median progression-free (overall) survival from the start of
reirradiation was 2.4 (4.6) months. CONCLUSION: Our analysis, although based on a
limited patient number, suggests that reirradiation of progressive non-pontine
HGG is feasible in children. Benefit in terms of quality of life and/or survival
needs to be assessed in a prospective and ideally in a randomized manner.
PMID- 25112659
TI - BDNF contributes to the facilitation of hippocampal synaptic plasticity and
learning enabled by environmental enrichment.
AB - Sensory, motor, and cognitive stimuli, resulting from interactions with the
environment, play a key role in optimizing and modifying the neuronal circuitry
required for normal brain function. An experimental animal model for this
phenomenon comprises environmental enrichment (EE) in rodents. EE causes profound
changes in neuronal and signaling levels of excitation and plasticity throughout
the entire central nervous system and the hippocampus is particularly affected.
The mechanisms underlying these changes are not yet fully understood. As brain
derived neurotrophic factor (BDNF) supports hippocampal long-term potentiation
(LTP), we explored whether it participates in the facilitation of synaptic
plasticity and hippocampus-dependent learning that occurs following EE. In the
absence of EE, LTP elicited by high-frequency stimulation was equivalent in
wildtype mice and heterozygous BDNF(+/-) siblings. LTP elicited by theta-burst
stimulation in BDNF(+/-) mice was less than in wildtypes. Long-term depression
(LTD) was also impaired. EE for three weeks, beginning after weaning, improved
hippocampal LTP in both wildtype and transgenic animals, with LTP in transgenics
achieving levels seen in wildtypes in the absence of EE. Object recognition
memory was evident in wildtypes 24 h and 7 days after initial object exposure. EE
improved memory performance in wildtypes 24 h but not 7 days after initial
exposure. BDNF(+/-) mice in the absence of EE showed impaired memory 7 days after
initial object exposure that was restored by EE. Western blotting revealed
increased levels of BDNF, but not proBDNF, among both EE cohorts. These data
support that BDNF plays an intrinsic role in improvements of synaptic plasticity
and cognition that occur in EE.
PMID- 25112660
TI - Subacute presentation of eyebrow intravascular papillary endothelial hyperplasia
causing ophthalmic nerve compression.
PMID- 25112661
TI - Percutaneous closure of patent foramen ovale in patients with cryptogenic
embolism: a network meta-analysis.
AB - BACKGROUND: Up to 40% of ischaemic strokes are cryptogenic. A strong association
between cryptogenic stroke and the prevalence of patent foramen ovale (PFO)
suggests paradoxical embolism via PFO as a potential cause. Randomized trials
failed to demonstrate superiority of PFO closure over medical therapy. METHODS
AND RESULTS: Randomized trials comparing percutaneous PFO closure against medical
therapy or devices head-to-head published or presented by March 2013 were
identified through a systematic search. We performed a network meta-analysis to
determine the effectiveness and safety of PFO closure with different devices when
compared with medical therapy. We included four randomized trials (2963 patients
with 9309 patient-years). Investigated devices were Amplatzer (AMP), STARFlex
(STF), and HELEX (HLX). Patients allocated to PFO closure with AMP were less
likely to experience a stroke than patients allocated to medical therapy [rate
ratio (RR) 0.39; 95% CI: 0.17-0.84]. No significant differences were found for
STF (RR 1.01; 95% CI: 0.44-2.41), and HLX (RR, 0.71; 95% CI: 0.17-2.78) when
compared with medical therapy. The probability to be best in preventing strokes
was 77.1% for AMP, 20.9% for HLX, 1.7% for STF, and 0.4% for medical therapy. No
significant differences were found for transient ischaemic attack and death. The
risk of new-onset atrial fibrillation was more pronounced for STF (RR 7.67; 95%
CI: 3.25-19.63), than AMP (RR 2.14; 95% CI: 1.00-4.62) and HLX (RR 1.33; 95%-CI
0.33-4.50), when compared with medical therapy. CONCLUSIONS: The effectiveness of
PFO closure depends on the device used. PFO closure with AMP appears superior to
medical therapy in preventing strokes in patients with cryptogenic embolism.
PMID- 25112665
TI - Combined detection of coronary artery disease and lung cancer.
PMID- 25112662
TI - The association between biventricular pacing and cardiac resynchronization
therapy-defibrillator efficacy when compared with implantable cardioverter
defibrillator on outcomes and reverse remodelling.
AB - AIMS: Previous studies on biventricular (BIV) pacing and cardiac
resynchronization therapy-defibrillator (CRT-D) efficacy have used arbitrarily
chosen BIV pacing percentages, and no study has employed implantable cardioverter
defibrillator (ICD) patients as a control group. METHODS AND RESULTS: Using
Kaplan-Meier plots, we estimated the threshold of BIV pacing percentage needed
for CRT-D to be superior to ICD on the end-point of heart failure (HF) or death
in 1219 left bundle branch block (LBBB) patients in the MADIT-CRT trial. Patients
were censored at the time of crossover. In multivariable Cox analyses, no
difference was seen in the risk of HF/death between ICD and CRT-D patients with
BIV pacing <=90% [HR = 0.78 (0.47-1.30), P = 0.344], and with increasing BIV
pacing the risk of HF/death was decreased [CRT-D BIV 91-96% vs. ICD: HR = 0.63
(0.42-0.94), P = 0.024 and CRT-D BIV >=97% vs. ICD: HR = 0.32 (0.23-0.44), P <
0.001]. The risk of death alone was reduced by 52% in CRT-D patients with BIV
>=97% (HR = 0.48, P < 0.016), when compared with ICD patients. Within the CRT-D
group, for every 1 percentage point increase in BIV pacing, the risk of HF/death
and death alone significantly decreased by 6 and 10%, respectively. Increasing
BIV pacing percentage was associated with significant reductions in left
ventricular volume. CONCLUSION: In patients with LBBB, who were in sinus rhythm
at enrolment, BIV pacing exceeding 90% was associated with a benefit of CRT-D in
HF/death when compared with ICD patients. Furthermore, BIV pacing >=97% was
associated with an even further reduction in HF/death, a significant 52%
reduction in death alone, and increased reverse remodelling. Clinical trials.gov
identifier: NCT00180271.
PMID- 25112666
TI - Verwijzen naar het hospice: verwijsgedrag van artsen en ervaren belemmeringen in
Deventer en omgeving.
AB - PHYSICIANS' REFERRAL PATTERNS AND PERCEIVED BARRIERS IN THE DEVENTER REGION IN
THE NETHERLANDS: OBJECTIVE: To examine physicians' perceived referral patterns
and barriers to referral of terminally ill patients to a hospice (institute).
DESIGN: Survey study among physicians practicing in hospital and other settings
in the region of Deventer, The Netherlands, in 2011-2012. METHOD: We translated
two available American instruments into Dutch. The questionnaire assessed hospice
referral, knowledge about hospice, attitudes and barriers and reasons not to
refer. We queried physicians who had referred patients to the local hospice about
expectations and suggested areas for improvement with two open-ended items.
RESULTS: In total, 240 physicians received the questionnaire. The response rate
was 47%. The physicians were generally positive about hospice care. They
indicated experiencing few barriers in hospice referrals, but 32% of the
physicians (21% of those practicing in the hospital, and 39% in other settings),
indicated the patient being unready as a strong barrier. Half of the physicians
(51%) believed that hospice is being underutilized and 22% (35% and 14%,
respectively) thought that they would refer more frequently if they had more
knowledge about hospice care. Of the physicians, 35% answered all six knowledge
questions correctly. Communication with the hospice may be improved. CONCLUSION:
Despite positive attitudes toward hospice care, it may be underutilized due to
poor knowledge and communication with the hospice. Perhaps, this is also due to
limited patient-physician communication on prognosis, which further research may
address.
PMID- 25112667
TI - [TRANSITION OF A PSYCHOGERIATRIC DAY CARE IN THE NURSING HOME TO EASY-ACCESS DAY
CARE PLUS CAREGIVER SUPPORT IN THE COMMUNITY: A PILOT STUDY].
AB - BACKGROUND: In this study, the transition of a nursing home based psychogeriatric
day care centre to an easy-access community day care centre plus caregiver
support (DC-plus CS) is followed closely. The transition was based on the proven
effective Meeting Centres Support Program. METHOD: By means of qualitative
analysis of documents and interviews with key persons (n=11) we investigate
facilitating and impeding factors for making this transition. Besides, we
evaluate the satisfaction of participants and informal caregivers that used the
new support program longer than 6 months. RESULTS: Several characteristics of the
innovation (DC-plus CS) help to establish cooperation with other care and welfare
services in the region, such as: the easy-access location, the social integration
in the community, and the focus on combined support for people with dementia and
their informal carers. The good cooperation and the suitable location in the
community facilitate the implementation. At first, the presence of other
community care-centres for people with dementia and their informal carers in the
neighbourhood impedes the recruitment of new participants for the DC-plus CS. In
general, the satisfaction of participants and informal carers about the support
program is high. CONCLUSION AND DISCUSSION: The transition is made successfully
and this study gives other psychogeriatric day care centres in the nursing home
insight in how to make a similar transition to DC-plus CS.
PMID- 25112668
TI - 'Soya milk Tris-based phytoextender reduces apoptosis in cryopreserved buffalo
(Bubalus bubalis) spermatozoa'.
AB - The objective of this study was to investigate the effect of newly developed soya
milk Tris (SMT)-based phytoextender as an alternative to egg yolk Tris (EYT)
extender used for cryopreservation of buffalo (Bubalus bubalis) spermatozoa on
apoptosis. Fresh buffalo semen (control without dilution) was cryopreserved in
conventional EYT (20% egg yolk v/v in Tris) and SMT (25% soya milk v/v in Tris)
extender and used for the assessment of expression of apoptotic proteins.
Proteins extracted from a total number of nine ejaculates from three individual
buffalo bulls chosen at random were separated using SDS-PAGE followed by
immunoblotting against caspase-8, caspase-9, caspase-3, poly(ADP
ribose)polymerase (PARP), cytochrome c and apoptosis inducing factor (AIF). In
addition, fluorescence microscopy was used for the detection of mitochondrial
membrane potential (JC-1 assay) and apoptotic cells (annexin V-FITC/PI assay).
The results obtained clearly indicate the significant (p < 0.05) reduction in the
expression of caspase-3 (27 kDa), caspase-8 (53 kDa), caspase-9 (50 kDa)
precursor and cytochrome c (17 kDa) in semen cryopreserved in SMT extender in
comparison with EYT extender. A non-significant (p > 0.05) reduction in
expression of PARP-DNA-binding subunit (24 kDa) was observed in SMT extender. No
expression of AIF was found in cryopreserved semen samples. A significant (p <
0.05) increase in the mean percentage of cells having high mitochondrial membrane
potential and a non-significant (p > 0.05) decrease in late apoptotic cells
(AN+/PI+) was observed in SMT extender when compared to EYT extender. The results
demonstrated that cryopreservation of buffalo semen in SMT-based phytoextender
can replace the traditional egg yolk extenders as it reduces the expression of
apoptotic proteins maintaining high mitochondrial membrane potential and gives
better protection to sperms in terms of its non-animal origin.
PMID- 25112669
TI - Comparison of pregnancy and lactation labeling for attention-deficit
hyperactivity disorder drugs marketed in Australia, the USA, Denmark, and the UK.
AB - BACKGROUND: Pregnancy and lactation labeling is presented in the officially
recognized product information (PI) accompanying prescription drugs to ensure
appropriate prescribing in pregnant and breastfeeding women. OBJECTIVE: The aim
of this study was to analyze pregnancy and lactation labeling in PI for attention
deficit hyperactivity disorder drugs marketed across countries and to compare
this information with respect to consistency and discrepancy. METHODS: We
manually surveyed PI for atomoxetine, methylphenidate, and modafinil marketed by
the same pharmaceutical companies in Australia, the USA, Denmark, and the UK. We
extracted information regarding data sources (animal and human data), risk to the
fetus or breastfed child, excretion in breast milk, and recommendations for use.
The extracted information was then analyzed and compared with respect to
consistency and discrepancy. RESULTS: Inter-country discrepancies were identified
with respect to both animal and human data sources presented, types of risks
listed in association with exposure during pregnancy and lactation, information
regarding excretion of the drug in breast milk, and recommendations for use.
Consistency was identified between PI for drugs marketed in the EU. CONCLUSION:
The study suggests that pregnancy and lactation labeling in PI for drugs marketed
by the same pharmaceutical companies depend on the country of marketing; this
raises concern about the reliability of PI documents as a useful source of
information for appropriate prescribing during pregnancy and lactation.
Discrepancies in this information can potentially lead to inappropriate
prescribing in pregnant and breastfeeding women, who may expose their fetuses and
breastfed children to unnecessary risks. At the same time, unjustified warnings
against breastfeeding may result in children being unnecessarily weaned from
being breastfed.
PMID- 25112670
TI - Response to "diffusion-weighted MR imaging findings in a growing problem: hepatic
alveolar echinococcosis".
PMID- 25112663
TI - Establishing reference values for central blood pressure and its amplification in
a general healthy population and according to cardiovascular risk factors.
AB - AIMS: Estimated central systolic blood pressure (cSBP) and amplification
(Brachial SBP-cSBP) are non-invasive measures potentially prognostic of
cardiovascular (CV) disease. No worldwide, multiple-device reference values are
available. We aimed to establish reference values for a worldwide general
population standardizing between the different available methods of measurement.
How these values were significantly altered by cardiovascular risk factors
(CVRFs) was then investigated. METHODS AND RESULTS: Existing data from population
surveys and clinical trials were combined, whether published or not. Reference
values of cSBP and amplification were calculated as percentiles for 'Normal' (no
CVRFs) and 'Reference' (any CVRFs) populations. We included 45,436 subjects out
of 82,930 that were gathered from 77 studies of 53 centres. Included subjects
were apparently healthy, not treated for hypertension or dyslipidaemia, and free
from overt CV disease and diabetes. Values of cSBP and amplification were
stratified by brachial blood pressure categories and age decade in turn, both
being stratified by sex. Amplification decreased with age and more so in males
than in females. Sex was the most powerful factor associated with amplification
with 6.6 mmHg (5.8-7.4) higher amplification in males than in females.
Amplification was marginally but significantly influenced by CVRFs, with smoking
and dyslipidaemia decreasing amplification, but increased with increasing levels
of blood glucose. CONCLUSION: Typical values of cSBP and amplification in a
healthy population and a population free of traditional CVRFs are now available
according to age, sex, and brachial BP, providing values included from different
devices with a wide geographical representation. Amplification is significantly
influenced by CVRFs, but differently in men and women.
PMID- 25112671
TI - Reply to: comment on: CT analysis of the effect of pirfenidone in patients with
idiopathic pulmonary fibrosis.
PMID- 25112672
TI - Diffusion-weighted MR imaging findings in a growing problem: hepatic alveolar
echinococcosis.
AB - Hepatic alveolar echinococcosis (AE) is a rare parasitic disease which simulates
slow growing malignant processes. Cross-sectional imaging techniques play
important role in differentiating between AE lesions and malignant processes such
as cholangiocellular carcinoma (CCC) and hepatocellular carcinoma (HCC).
Diffusion-weighted (DW) MRI is a non-invasive technique, which can be used for
liver lesion detection and characterisation as benign or malignant in recent
years. Both conventional MRI and non-contrast enhanced CT images may be
insufficient the differential diagnosis in hepatic AE lesions particularly in
solid components. In our study, we have performed to differentiate hepatic AE
lesions from HCC and CCC lesions of the liver by using DW MRI and tried to define
ADC value of hepatic AE lesions for differentiation from malignant hepatic
lesions.
PMID- 25112673
TI - Incidence and classification of neointimal proliferation and in-stent restenosis
in post-stenting patients at 1-year interval: findings from non-invasive coronary
computed tomography angiography.
AB - OBJECTIVES: To evaluate the incidence of coronary in-stent restenosis (ISR) and
neointimal proliferation by coronary CT angiography (CCTA) at 1-year follow-up in
asymptomatic patients. METHODS: 234 patients (mean age: 67 +/- 10.2 years, range
39-88 years, 180 males and 54 females) with 379 stents were prospectively
enrolled in this study. Binary ISR was classified by CCTA into 4 types using
Mehran classification. Neointimal proliferation was similarly classified into
focal and diffuse types. All patients with CCTA-revealed ISR or neointimal
proliferation underwent further invasive coronary angiography (ICA) for
validation. Fisher's exact test was used for comparison. RESULTS: ICA revealed
patent stents with neointimal proliferation in 39 patients (16.7%, 39/234) and
binary ISR in 23 patients (9.8%, 23/234). Lesion-based analysis showed 12 type I
ISR lesions, 4 type II ISR lesions, 1 type III ISR lesion and 7 type IV ISR
lesions. Among cases with neointimal proliferation, 27 lesions were classified as
focal type whereas 13 lesions were classified as diffuse type. Patients with
diabetes mellitus were associated with higher incidence of CCTA-revealed
neointimal proliferation (21/77 vs. 18/157, p=0.002) as well as ISR (12/77 vs.
11/157, p=0.038), compared to patients without diabetes. CCTA was found to have
good diagnostic performance for neointimal proliferation and ISR detection as
well as classification, with an overall accuracy of 84.4% (54/64). CONCLUSIONS:
Silent ISR as well as neointimal proliferation is not uncommon findings in
asymptomatic post-stenting patients at 1-year interval, as revealed by CCTA.
Patients with diabetes are prone to have higher incidence of neointimal
proliferation.
PMID- 25112674
TI - Laboratory tests during direct oral anticoagulant treatment?
PMID- 25112676
TI - Chronic Stress Decreases Basal Levels of Memory-Related Signaling Molecules in
Area CA1 of At-Risk (Subclinical) Model of Alzheimer's Disease.
AB - An important factor that may affect the severity and time of onset of Alzheimer's
disease (AD) is chronic stress. Epidemiological studies report that chronically
stressed individuals are at an increased risk for developing AD. The purpose of
this study was to reveal whether chronic psychosocial stress could hasten the
appearance of AD symptoms including changes in basal levels of cognition-related
signaling molecules in subjects who are at risk for the disease. We investigated
the effect of chronic psychosocial stress on basal levels of memory-related
signaling molecules in area CA1 of subclinical rat model of AD. The subclinical
symptomless rat model of AD was induced by osmotic pump continuous
intracerebroventricular (ICV) infusion of 160 pmol/day Abeta1-42 for 14 days.
Rats were chronically stressed using the psychosocial stress intruder model.
Western blot analysis of basal protein levels of important signaling molecules in
hippocampal area CA1 showed no significant difference between the subclinical AD
rat model and control rat. Following six weeks of psychosocial stress, molecular
analysis showed that subclinical animals subjected to stress have significantly
reduced basal levels of p-CaMKII and decreased p-CaMKII/t-CaMKII ratio as well as
decreased basal levels of p-CREB, total CREB, and BDNF. The present results
suggest that these changes in basal levels of signaling molecules may be
responsible for impaired learning, memory, and LTP in this rat model, which
support the proposition that chronic stress may accelerate the emergence of AD in
susceptible individuals.
PMID- 25112677
TI - Identification and Expression of Acetylcholinesterase in Octopus vulgaris Arm
Development and Regeneration: a Conserved Role for ACHE?
AB - Acetylcholinesterase (ACHE) is a glycoprotein with a key role in terminating
synaptic transmission in cholinergic neurons of both vertebrates and
invertebrates. ACHE is also involved in the regulation of cell growth and
morphogenesis during embryogenesis and regeneration acting through its non
cholinergic sites. The mollusk Octopus vulgaris provides a powerful model for
investigating the mechanisms underlying tissue morphogenesis due to its high
regenerative power. Here, we performed a comparative investigation of arm
morphogenesis during adult arm regeneration and embryonic arm development which
may provide insights on the conserved ACHE pathways. In this study, we cloned and
characterized O. vulgaris ACHE, finding a single highly conserved ACHE
hydrophobic variant, characterized by prototypical catalytic sites and a putative
consensus region for a glycosylphosphatidylinositol (GPI)-anchor attachment at
the COOH-terminus. We then show that its expression level is correlated to the
stage of morphogenesis in both adult and embryonic arm. In particular, ACHE is
localized in typical neuronal sites when adult-like arm morphology is established
and in differentiating cell locations during the early stages of arm
morphogenesis. This possibility is also supported by the presence in the ACHE
sequence and model structure of both cholinergic and non-cholinergic sites. This
study provides insights into ACHE conserved roles during processes of arm
morphogenesis. In addition, our modeling study offers a solid basis for
predicting the interaction of the ACHE domains with pharmacological blockers for
in vivo investigations. We therefore suggest ACHE as a target for the regulation
of tissue morphogenesis.
PMID- 25112678
TI - Complexin-1 and Foxp1 Expression Changes Are Novel Brain Effects of Alpha
Synuclein Pathology.
AB - As the second most frequent neurodegenerative disorder of the aging population,
Parkinson's disease (PD) is characterized by progressive deficits in spontaneous
movement, atrophy of dopaminergic midbrain neurons and aggregation of the protein
alpha-synuclein (SNCA). To elucidate molecular events before irreversible cell
death, we studied synucleinopathy-induced expression changes in mouse brain and
identified 49 midbrain/brainstem-specific transcriptional dysregulations. In
particular complexin-1 (Cplx1), Rabl2a and 14-3-3epsilon (Ywhae) downregulation,
as well as upregulation of the midbrain-specific factor forkhead box P1 (Foxp1)
and of Rabgef1, were interesting as early mRNA level effects of alpha-synuclein
triggered pathology. The protein levels of complexin-1 were elevated in
midbrain/brainstem tissue of mice with A53T-SNCA overexpression and of mice with
SNCA-knockout. The response of CPLX1 and Foxp1 levels to SNCA deficiency supports
the notion that these factors are regulated by altered physiological function of
alpha-synuclein. Thus, their analysis might be useful in PD stages before the
advent of Lewy pathology. Because both alpha-synuclein and complexin-1 modulate
vesicle release, our findings support presynaptic dysfunction as an early event
in PD pathology.
PMID- 25112680
TI - The Neuroprotection of Lysosomotropic Agents in Experimental Subarachnoid
Hemorrhage Probably Involving the Apoptosis Pathway Triggering by Cathepsins via
Chelating Intralysosomal Iron.
AB - alpha-Lipoic acid-plus (LAP), an amine derivative of alpha-lipoic acid (LA),
could protect cells against oxidant challenges via chelating intralysosomal iron.
However, the application of LAP in experimental subarachnoid hemorrhage (SAH) is
still not well known. This study was designed to evaluate the potential
neuroprotection of LAP on the early brain injury (EBI) and the underlying
mechanisms in a rat model of SAH. The SAH models were induced in Sprague-Dawley
rats. LA and LAP were oral administration and lasted for 72 h once a day. The
brain tissue samples were obtained for assay at 72 h after SAH. In experiment 1,
we found that lysosome amounts in neurons decreased significantly in SAH group,
and LAP (100 mg/kg) could stabilize lysosomal membrane markedly based on
lysosomal-associated membrane protein-1 (LAMP-1) expression in neurons by
immunofluorescence. Hence, the LAP dosages of 100 and 150 mg/kg were applied in
experiment 2. Firstly, Western blot analysis showed that the protein levels of
cathepsin B/D, caspase-3, Bax, ferritin, and heme-oxygenase-1 (HO-1) markedly
increased after SAH, which were further confirmed by double immunofluorescence
staining and reversed by LA and LAP treatments. In addition, LA and LAP also
reduced oxidative stress and iron deposition in brain tissue. Furthermore, LA and
LAP significantly ameliorated brain edema, blood-brain barrier injury, cortical
apoptosis, and neurological behavior impairment induced by SAH. Finally, it is
noteworthy that LAP exerted more significant effects than LA on these parameters
as described above. LAP probably exerted neuroprotective effects via targeting
lysosomes and chelating intralysosomal iron in EBI post-SAH in rats.
PMID- 25112681
TI - Investigation of effect of 17alpha-ethinylestradiol on vigilin expression using
an isolated recombinant antibody.
AB - Vigilin, a highly conserved protein from yeast to mammals, is a multifunctional
protein in eukaryotic organisms. One biological function of vigilin is to
stabilize the expression level of vitellogenin (VTG). This study aimed to develop
vigilin as a new estrogen-inducible biomarker that correlates with the widely
applied estrogen-inducible biomarker VTG and expand the ability to detect it in
various species. Here, a recombinant monoclonal antibody with high specificity
against the conserved C-terminal region of vigilin from zebrafish (Danio rerio)
was successfully isolated from a phage display antibody library and found to
recognize vigilin proteins from multiple vertebrate species. The effect of
17alpha-ethinylestradiol (EE2) on vigilin expression in the liver of zebrafish
and juvenile crucian carp (Carassius auratus) was investigated. Although vigilin
mRNA was expressed in all tissues analyzed from male zebrafish, vigilin protein
was detected exclusively in the testis of male zebrafish, as well as the liver of
female zebrafish and juvenile crucian carp at a lower level without exposure to
EE2. Significant induction of vigilin mRNA by exposure to EE2 was observed in the
liver and testis of male zebrafish, even at a low dose of 6.25 ng/L (21.09
pmol/L). In Hela cells, the expression of vigilin coincided with high protein
synthesis activity but not dose-dependently by EE2 exposure. Therefore, the
recombinant antibody may be used as a detection tool to screen for mammalian cell
lines or organs with estrogen-inducible expression of vigilin.
PMID- 25112682
TI - Gene markers of generic Escherichia coli associated with colonization and
persistence of Escherichia coli O157 in cattle.
AB - Enterohemorrhagic Escherichia coli (EHEC) O157 are important foodborne pathogens
whose major reservoir are asymptomatic cattle. There is evidence suggesting that
nonpathogenic E. coli and bacteriophages in the gastro-intestinal tract can
influence the pathogenicity of EHEC O157. The factors contributing to the onset
and persistence of shedding EHEC O157 in cattle are not completely elucidated.
This study used Bayesian network analysis to identify genetic markers of generic
E. coli associated with shedding of EHEC O157 in cattle from data generated
during an oral experimental challenge study in 4 groups of 6 steers inoculated
with three different EHEC O157 strains. The quantification of these associations
was accomplished using mixed effects logistic regression. The results showed that
the concurrent presence of generic E. coli carrying the prophage marker R4-N and
the virulence marker stx2 increased the odds of the onset of EHEC O157 shedding.
The presence of prophage markers z2322 and X011C increased, while C1.N decreased
the odds of shedding EHEC O157 two days later. A significant antagonist
interaction effect between the presence of the virulence marker stx2 on the day
of shedding EHEC O157 and two days before shedding was also found. In terms of
the persistence of EHEC O157 shedding, the presence of prophage marker R4-N
(OR=16, and 95% confidence interval (CI): 1.1, 252) was found to increase the
odds of stopping EHEC O157 shedding, whereas prophage marker C1.N (OR=0.16, CI:
0.03, 0.7) and the enterohemolysin gene hly (OR=0.03, CI: 0.001, 0.8) were found
to significantly decrease the odds of stopping EHEC O157 shedding. In conclusion,
the study found that the presence of certain genetic markers in the generic E.
coli genome can influence the pathogenicity of EHEC O157.
PMID- 25112679
TI - Ceftriaxone Protects Astrocytes from MPP(+) via Suppression of NF-kappaB/JNK/c
Jun Signaling.
AB - Ceftriaxone has been shown to attenuate the dopaminergic neuron death and
alleviate behavioral disorders in Parkinson's disease models via upregulation of
glutamate transporter-1 (GLT-1) and decreases in extracellular glutamate.
However, details of how this neuroprotection occurs are uncertain. We
hypothesized that cytoprotection by ceftriaxone in astrocytes exposed to 1-methyl
4-phenylpyridinium (MPP(+)) involves suppression of the NF-kappaB/JNK/c-Jun
signaling pathway. Here, we observed a protective effect of ceftriaxone in
primary astrocytes exposed to MPP(+). Ceftriaxone enhanced glutamate uptake and
promoted primary astrocyte viability after MPP(+) exposure. Ceftriaxone enhances
glutamate uptake via upregulation of GLT-1 in the plasma membrane, and alleviates
MPP(+)-induced neurotoxicity via suppression of NF-kappaB/JNK/c-Jun signaling.
Collectively, our data offer evidence that increased expression and function of
GLT-1 are involved in the protective mechanism of ceftriaxone in astrocytes
exposed to MPP(+) in vitro, and we offer insight into the potential therapeutic
role of ceftriaxone in treatment of Parkinson's disease.
PMID- 25112683
TI - Subcellular neural probes from single-crystal gold nanowires.
AB - Size reduction of neural electrodes is essential for improving the functionality
of neuroprosthetic devices, developing potent therapies for neurological and
neurodegenerative diseases, and long-term brain-computer interfaces. Typical
neural electrodes are micromanufactured devices with dimensions ranging from tens
to hundreds of micrometers. Their further miniaturization is necessary to reduce
local tissue damage and chronic immunological reactions of the brain. Here we
report the neural electrode with subcellular dimensions based on single
crystalline gold nanowires (NWs) with a diameter of ~100 nm. Unique mechanical
and electrical properties of defect-free gold NWs enabled their implantation and
recording of single neuron-activities in a live mouse brain despite a ~50*
reduction of the size compared to the closest analogues. Reduction of electrode
dimensions enabled recording of neural activity with improved spatial resolution
and differentiation of brain activity in response to different social situations
for mice. The successful localization of the epileptic seizure center was also
achieved using a multielectrode probe as a demonstration of the diagnostics
potential of NW electrodes. This study demonstrated the realism of single-neuron
recording using subcellular-sized electrodes that may be considered a pivotal
point for use in diverse studies of chronic brain diseases.
PMID- 25112685
TI - Green condensation reaction of aromatic aldehydes with active methylene compounds
catalyzed by anion-exchange resin under ultrasound irradiation.
AB - To realize a practical and green chemistry, two important challenges need to be
addressed, namely the effective process for the activation of reaction and
efficient, eco-friendly and robust chemical methods for the reaction conversion
to target products via highly selective catalytic and reactions. Ultrasonic
energy promotes the conversion process through its special cavitational effects.
Combined with anion-exchange resin as a heterogeneous, reusable and efficient
catalyst, Ultrasonic energy enhances the Knoevenagel condensation and leads to
reduced reaction time at lower reaction temperature with less amounts of solvent
and catalyst.
PMID- 25112684
TI - Sensitivity of free radicals production in acoustically driven bubble to the
ultrasonic frequency and nature of dissolved gases.
AB - Central events of ultrasonic action are the bubbles of cavitation that can be
considered as powered microreactors within which high-energy chemistry occurs.
This work presents the results of a comprehensive numerical assessment of
frequency and saturating gases effects on single bubble sonochemistry. Computer
simulations of chemical reactions occurring inside a bubble oscillating in liquid
water irradiated by an ultrasonic wave have been performed for a wide range of
ultrasonic frequencies (213-1100kHz) under different saturating gases (O2, air,
N2 and H2). For O2 and H2 bubbles, reactions mechanism consisting in 25
reversible chemical reactions were proposed for studying the internal bubble
chemistry whereas 73 reversible reactions were taken into account for air and N2
bubbles. The numerical simulations have indicated that radicals such as OH, H,
HO2 and O are created in the bubble during the strong collapse. In all cases,
hydroxyl radical (OH) is the main oxidant created in the bubble. The production
rate of the oxidants decreases as the driving ultrasonic frequency increases. The
production rate of OH radical followed the order O2>air>N2>H2 and the order
becomes more remarkable at higher ultrasonic frequencies. The effect of
ultrasonic frequency on single bubble sonochemistry was attributed to its
significant impact on the cavitation process whereas the effects of gases were
attributed to the nature of the chemistry produced in the bubble at the strong
collapse. It was concluded that, in addition to the gas solubility, the nature of
the internal bubble chemistry is another parameter of a paramount importance that
controls the overall sonochemical activity in aqueous solutions.
PMID- 25112686
TI - Current or voltage? Another Shakespearean dilemma.
PMID- 25112688
TI - Infection rates of Linguatula serrata nymphs in mesenteric lymph nodes from water
buffaloes in North India.
AB - The literature pertaining to prevalence of Linguatula serrata in large ruminants
is limited. In abattoir survey, the infection rate of L. serrata in 1440
mesenteric lymph nodes collected from 480 buffaloes from North India was
investigated. Results revealed 88 (18.3%) buffaloes and 288 (20.0%) mesenteric
lymph nodes having parasite's nymphs. Nonsignificant difference (P>0.05), between
1 and 3 years age (51.5%) and above three years of age (48.5%) groups was
observed. Nonsignificant difference (P>0.05) between the infection rate of male
(51.5%) and female (48.5%) was also observed. Infection in haemorrhagic (57.2%)
and black-coloured (67.5%) nymph nodes were significantly (P<0.05) higher than
normal-coloured nodes (8.8%). When compared based on consistency, the results
showed soft lymph nodes (61.3%) were significantly (P<0.05) more infected than
normal (12.8%) and hard (30.0%) lymph nodes. The intensity of infection in
normal, haemorrhagic and black lymph nodes were 1.81 +/- 0.21, 4.23 +/- 0.0.62
and 5.12 +/- 0.73, nymphs respectively. The mean numbers of parasites in
haemorrhagic and black-coloured lymph nodes were significantly (P<0.0005) more
than mean number of parasites in normal-coloured nodes. Again intensity of
infection in normal, soft and hard lymph nodes was 2.31 +/- 0.18, 5.84 +/- 0.74
and 3.21 +/- 0.68, respectively. When compared based on lymph nodes consistency,
the soft lymph nodes were significantly (P<0.0005) more severely infected than
normal and hard ones. The study has generated some vital data about the
prevalence of this underreported disease amongst the bubaline intermediate hosts
along with important gross changes in the affected lymph nodes.
PMID- 25112687
TI - Identification of new novel scaffold for Aurora A inhibition by pharmacophore
modeling and virtual screening.
AB - Aurora kinases belong to family of highly conserved serine/threonine protein
kinases that are involved in diverse cell cycle events and play a major role in
regulation of cell division. Abnormal expression of Aurora kinases may lead to
cancer; hence, these are considered as a potential target in cancer treatment. In
this research article, we identified three novel Aurora A inhibitors using modern
computational tools. A four-point common 3D pharmacophore hypothesis of Aurora A
(AurA) inhibitors was developed using a diverse set of 55 thienopyrimidine
derivatives. A three-dimensional quantitative structure-activity relationship (3D
QSAR) study was carried out using atom-based alignment of diverse set of 55
molecules to evaluate the structure- activity relationships. Docking and 3D-QSAR
studies were performed with the 3D structure of AurA to evaluate the generated
pharmacophore. The pharmacophore model and 3D-QSAR results complemented the
results of our docking study. The pharmacophore hypothesis, which yields the best
results, was used to screen the Zinc 'clean drug-like' database. Various database
filters such as 3D-arrangement of pharmacophoric features, predicted activity and
binding interaction score were used to retrieve hits having potential AurA
inhibition activity.
PMID- 25112689
TI - Membrane disruptive antimicrobial activities of human beta-defensin-3 analogs.
AB - Human beta defensin-3 (HbetaD-3) is a host-defense protein exhibiting
antibacterial activity towards both Gram-negative and Gram-positive bacteria.
There is considerable interest in the function of this protein due to its
increased salt tolerance and activity against Gram-positive Staphylococcus
aureus. In this study, analogs of HbetaD-3 devoid of N and C terminal regions are
investigated to determine the influence of specific structural motif on
antimicrobial activity and selectivity between Gram-positive and Gram-negative
bacteria. Circular dichroism, fluorescence and solid-state NMR experiments have
been used to investigate the conformation and mode of action of HbetaD3 analogs
with various model membranes to mimic bacterial inner and outer membranes and
also mammalian membranes. Our studies specifically focused on determining four
major characteristics: (i) interaction of HbetaD3 analogs with phospholipid
vesicles composed of zwitterionic PC or anionic PE:PG vesicles and LPS; (ii)
conformation of HbetaD3-peptide analogs in the presence of PC or PE:PG vesicles;
(iii) ability of HbetaD3 analogs to permeate phospholipid vesicles composed of PC
or PE:PG; and (iv) activities on bacteria cells and erythrocytes. Our results
infer that the linear peptide L25P and its cyclic form C25P are more active than
L21P and C21P analogs. However, they are less active than the parent peptide,
thus pointing towards the importance of the N terminal domain in its biological
activity. The variation in the activities of L21P/C21P and L25P/C25P also suggest
the importance of the positively charged residues at the C terminus in providing
selectivity particularly to Gram-negative bacteria.
PMID- 25112691
TI - Anthropometric indices are not satisfactory predictors of metabolic comorbidities
in obese children and adolescents.
AB - OBJECTIVE: To assess the accuracy of body mass index (BMI), Z score of the BMI,
waist circumference, and waist-to-height ratio in selecting obese children with
fasting metabolic impairments or impaired glucose tolerance. STUDY DESIGN: In a
cohort of 883 obese children and adolescents (age 8-18 years), we assessed the
associations of anthropometric indices with traditional metabolic complications
of obesity (impaired fasting glucose, impaired glucose tolerance, hypertension,
high triglycerides, low high-density lipoprotein-cholesterol). The accuracy of
anthropometric indices as markers of metabolic impairment was assessed by
receiver operating characteristic analysis and the areas under the receiver
operating characteristics curves (AUROCs) of anthropometric indices were compared
with each other by the DeLong test. RESULTS: BMI, Z score of the BMI, waist
circumference, and waist-to-height ratio were associated with metabolic
impairments but showed low to moderate accuracy in discriminating both single and
clustered metabolic impairments. The AUROCs ranged from 0.55-0.70. The 4
anthropometric indices did not show significantly different AUROCs as predictors
of clustered metabolic risk factors (all P values of DeLong tests: >.05).
CONCLUSIONS: Commonly used anthropometric indices are not satisfactory markers of
metabolic comorbidity among obese children and adolescents and should not be
adopted as screening tools for the metabolic assessment of this category of
patients.
PMID- 25112690
TI - Conformational studies of chiral D-Lys-PNA and achiral PNA system in binding with
DNA or RNA through a molecular dynamics approach.
AB - The growing interest in peptide nucleic acid (PNA) oligomers has led to the
development of a very wide variety of PNA derivatives. Among others, the
introduction of charged chiral groups on a PNA oligomer has proven effective in
improving DNA binding ability, complexation direction and cellular uptake. In
particular, the introduction of three adjacent chiral monomers based on D-Lys in
the middle of the PNA sequence (D-Lys-PNA) has produced noteworthy results in
modulating the directionality of the binding with the DNA complementary strand
and in mismatch detection. Here, through a molecular dynamics approach, a
comparative study has been carried out to investigate the structural properties
that drive the interaction of the chiral D-Lys-PNA and the corresponding achiral
PNA system with DNA as well as RNA complementary strands, starting from the
crystal structure of D-Lys-PNA in complex with DNA. The results obtained
complement experimental data and indicate that the binding with the RNA molecule,
compared to DNA, is differently affected by the addition of three D-Lys groups on
the PNA backbone, suggesting that this modification could be taken into account
for the development of new PNA-based molecules able to discriminate between DNA
and RNA.
PMID- 25112692
TI - Association of Clostridium difficile infections with acid suppression medications
in children.
AB - OBJECTIVE: Multiple studies have confirmed associations between acid suppression
medication and Clostridium difficile infections (CDIs) in adults. Therefore, we
sought to evaluate an association between acid suppression medications and CDI in
children. STUDY DESIGN: A retrospective self-controlled case series was performed
utilizing billing records from the TRICARE Management Activity military health
system database. Children ages 2-18 years from October 1, 2001 to July 31, 2013,
who had an outpatient or inpatient record of CDI diagnosis were included. The
relative incidences (RIs) of CDI or recurrent CDI were calculated comparing time
periods prescribed and not prescribed proton pump inhibitors (PPIs) or histamine
2 receptor antagonists (H2RAs). RESULTS: There were 2531 cases of CDI among 2437
patients, and 1190 (48.8%) were prescribed acid suppression medications. CDI were
more likely to occur during periods when patients were prescribed a PPI (RI 2.36;
95% CI 2.22-2.52), H2RA (RI 1.95; 95% CI 1.63-2.34), or during periods while
prescribed both simultaneously (RI 2.40; 95% CI 1.90-3.04). There were 265
(10.4%) cases that were classified as recurrent among 217 (8.9%) patients.
Recurrent CDI also was found to be more likely during prescription periods of PPI
(RI 1.74; 95% CI 1.51-2.00) and H2RA (RI 2.63; 95% CI 1.89-3.66). CONCLUSIONS:
Acid suppression medications are associated with an increased risk of CDI and
recurrent CDI. Judicious use of acid suppression medication should be considered,
especially among those at highest risk for CDI.
PMID- 25112693
TI - Factors affecting the natural decay of hepatitis B surface antigen in children
with chronic hepatitis B virus infection during long-term follow-up.
AB - OBJECTIVE: To investigate the factors predicting spontaneous clearance of
hepatitis B surface antigen (HBsAg) in a long-term, prospectively followed cohort
from childhood into adult life. STUDY DESIGN: Children with chronic hepatitis B
virus (HBV) infection without treatment were followed longitudinally every 6
months. At each visit, liver profiles and HBV markers were assessed. Hepatitis B
vaccination history and the maternal HBV markers also were studied. RESULTS: A
total of 349 children (205 male) were followed for 20.6 +/- 4.4 years with
initial ages of 8.4 +/- 3.9 years; 42 (12.0%) cleared HBsAg spontaneously. The
HBsAg titers decayed with age, with an average annual clearance rate of 0.58%.
Children had a lower annual HBsAg decay rate if their mothers are HBsAg carriers
(P < .001). Hepatitis B e antigen-seroconversion is a favorable predictor for
spontaneous HBsAg clearance (P = .04). Those with HBsAg titer <=1000 IU/mL at
enrollment during childhood have a higher rate of HBsAg clearance (hazard ratio =
5.23; P < .001). Using HBsAg titer <=1000 IU/mL to predict HBsAg clearance, the
sensitivity is 38.1%, specificity is 90.6%, positive predictive value is 35.6%,
and negative predictive value is 91.4%. CONCLUSIONS: During long-term follow-up,
spontaneous HBsAg clearance is most likely to occur in a patient born to a non
HBsAg-carrier mother, is a hepatitis B e antigen-seroconverter, and had an
initial HBsAg level <=1000 IU/mL.
PMID- 25112694
TI - Heart rate variability and cardiovascular risk factors in adolescent boys.
AB - OBJECTIVE: To establish reference values of heart rate variability (HRV) measures
in a cohort of adolescent boys and to determine the relationship between HRV and
the clustering of risk factors (RFs) for cardiovascular disease. STUDY DESIGN:
This cross-sectional study included 1152 adolescent boys (age: 16.6 +/- 1.2 years
old). Demographic data, health-related habits, obesity indicators, and blood
pressure were evaluated. HRV measures of time (SD of all RR intervals, root mean
square of the squared differences between adjacent normal RR intervals, and the
percentage of adjacent intervals over 50 ms) and frequency domains were assessed
(low [LF] and high [HF] frequency). RESULTS: The components of HRV were RR
interval (827 +/- 128 ms), SD of all RR intervals (61.9 +/- 23.5 ms), root mean
square of the squared differences between adjacent normal RR intervals (54.5 +/-
29.4 ms), percentage of adjacent intervals over 50 ms (29.4 +/- 20.4%), LF (53 +/
16 nu), HF (47 +/- 16), and LF/HF (1.44 +/- 1.08). Greater sympathetic and lower
parasympathetic modulation at rest were associated with higher adiposity, higher
blood pressure and physical inactivity. Adolescents with 2 or more RFs also
presented lower HRV than subjects with no RFs (P < .001). CONCLUSIONS: The study
has provided descriptive indicators that help the interpretation of HRV results
in adolescents. Lower HRV measures are associated with the clustering of
cardiovascular RFs.
PMID- 25112695
TI - Reliability of circulatory and neurologic examination by telemedicine in a
pediatric intensive care unit.
AB - OBJECTIVE: To test the hypothesis that telemedicine can reliably be used for many
aspects of circulatory and neurologic examinations of children admitted to a
pediatric intensive care unit (PICU). STUDY DESIGN: A prospective, randomized
study in a 14-bed PICU in a tertiary care, academic-affiliated institution.
Eligible patients were >2 months or <19 years of age, not involved in a
concurrent study, had parents/guardian able to sign an informed consent form,
were not at end-of-life, and had an attending who not only deemed them medically
stable, but also felt that the study would not interrupt their care. Other than
the Principal Investigator, 6 pediatric intensivists and 7 pediatric critical
care fellows were eligible study providers. Two physician providers were randomly
assigned to perform circulatory and neurologic examinations according to the
American Heart Association/Pediatric Advanced Life Support guidelines in-person
and via telemedicine. Findings were recorded on a standardized data collection
form and compared. RESULTS: One hundred ten data collection forms were completed.
For many aspects of the circulatory and neurologic examinations, outcomes showed
substantial to perfect agreement between the in-person and telemedical care
providers (kappa = 0.64-1.00). However, assessments of muscle tone had a kappa =
0.23, with a kappa = 0.37 for skin color. CONCLUSIONS: Telemedicine can reliably
identify normal and abnormal findings of many aspects of circulatory and
neurologic examinations in PICU patients. This finding opens the door to further
studies on the use of telemedicine across other disciplines.
PMID- 25112696
TI - Breech labour is not a particular indication for STAN monitoring.
PMID- 25112698
TI - Classification of common variable immunodeficiencies using flow cytometry and a
memory B-cell functionality assay.
AB - BACKGROUND: The population of patients with common variable immunodeficiency
(CVID) comprises a heterogeneous group of patients with different causes of
hypogammaglobulinemia predisposing to recurrent infections, higher incidence of
autoimmunity, and malignancy. Although memory B cells (memBcs) are key players in
humoral defense and their numbers are commonly reduced in these patients, their
functionality is not part of any current classification. OBJECTIVE: We
established and validated a memBc enzyme-linked immunosorbent spot (ELISpot)
assay that reveals the capacity of memBcs to develop into antibody-secreting
cells and present an idea for a new classification based on this functional
capacity. METHODS: The memBc ELISpot assay, combined with flow cytometry, was
applied to patients with confirmed CVID in comparison with age-matched healthy
control subjects. RESULTS: Ex vivo frequency of IgG-, IgM-, and IgA-secreting
plasmablasts was significantly diminished by 27.2-, 2.4-, and 23.3-fold,
respectively, compared with that seen in healthy control subjects. Moreover, in
vitro differentiation of memBcs into antibody-secreting cells was 6.1-, 2.6-, and
3.7-fold significantly reduced for IgG-, IgM-, and IgA-secreting cells,
respectively. Proliferation of memBcs correlates inversely to immunoglobulin
secreting capacity, suggesting compensatory hyperproliferation. Furthermore,
patients with no serum IgA can still have a detectable IgA ELISpot assay result
in vitro. Most importantly, the large heterogeneity of memBc function in patients
with CVID homogenously grouped by means of fluorescence-activated cell sorting
allowed additional subclassification based on memBc/plasmablast function.
CONCLUSION: These data suggest almost normal memBc/immunoglobulin-secreting
plasmablast functionality in some patients if sufficient stimulatory signals are
delivered, which might open up opportunities for new therapeutic approaches.
PMID- 25112699
TI - IL-9 is a key component of memory TH cell peanut-specific responses from children
with peanut allergy.
AB - BACKGROUND: Differentiation between patients with peanut allergy (PA) and those
with peanut sensitization (PS) who tolerate peanut but have peanut-specific IgE,
positive skin prick test responses, or both represents a significant diagnostic
difficulty. Previously, gene expression microarrays were successfully used to
identify biomarkers and explore immune responses during PA immunotherapy.
OBJECTIVE: We aimed to characterize peanut-specific responses from patients with
PA, subjects with PS, and atopic children without peanut allergy (NA children).
METHODS: A preliminary exploratory microarray investigation of gene expression in
peanut-activated memory TH subsets from 3 children with PA and 3 NA children
identified potential PA diagnostic biomarkers. Microarray findings were confirmed
by using real-time quantitative PCR in 30 subjects (12 children with PA, 12
children with PS, and 6 NA children). Flow cytometry was used to identify the TH
subsets involved. RESULTS: Among 12,257 differentially expressed genes, IL9
showed the greatest difference between children with PA and NA children (45.59
fold change, P < .001), followed by IL5 and then IL13. Notably, IL9 allowed the
most accurate classification of children with PA and NA children by using a
machine-learning approach with recursive feature elimination and the random
forest algorithm. Skin- and gut-homing TH cells from donors with PA expressed
similar TH2- and TH9-associated genes. Real-time quantitative PCR confirmed that
IL9 was the highest differentially expressed gene between children with PA and NA
children (23.3-fold change, P < .01) and children with PS (18.5-fold change, P <
.05). Intracellular cytokine staining showed that IL-9 and the TH2-specific
cytokine IL-5 are produced by distinct TH populations. CONCLUSION: In this study
IL9 best differentiated between children with PA and children with PS (and atopic
NA children). Mutually exclusive production of IL-9 and the TH2-specific cytokine
IL-5 suggests that the IL-9-producing cells belong to the recently described TH9
subset.
PMID- 25112697
TI - "Auto-anti-IgE": naturally occurring IgG anti-IgE antibodies may inhibit allergen
induced basophil activation.
AB - BACKGROUND: Naturally occurring IgE-specific IgG autoantibodies have been
identified in patients with asthma and other diseases, but their spectrum of
functions is poorly understood. OBJECTIVE: Address the hypothesis that: (i) IgG
anti-IgE autoantibodies are detectable in the serum of all subjects but elevated
in asthmatic patients regardless of atopic status as compared with controls; (ii)
some activate IgE-sensitized basophils; and (iii) some inhibit allergen-induced
basophil activation. METHODS: IgE-specific IgG autoantibodies were detected and
quantified in sera using ELISA. Sera were examined for their ability to activate
IgE-sensitized human blood basophils in the presence and absence of allergen
using a basophil activation test, and to inhibit allergen binding to specific IgE
on a rat basophilic cell line stably expressing human FcepsilonRI. RESULTS: IgG
autoantibodies binding to both free and FcepsilonRI-bound IgE were detected in
patients with atopic and non-atopic asthma, as well as controls. While some were
able to activate IgE-sensitised basophils, others inhibited allergen-induced
basophil activation, at least partly by inhibiting binding of IgE to specific
allergen. CONCLUSION: Naturally occurring IgG anti-IgE autoantibodies may
inhibit, as well as induce, basophil activation. They act in a manner distinct
from therapeutic IgG anti-IgE antibodies such as omalizumab. They may at least
partly explain why atopic subjects who make allergen-specific IgE never develop
clinical symptoms, and why omalizumab therapy is of variable clinical benefit in
severe atopic asthma.
PMID- 25112700
TI - IL-33 promotes GATA-3 polarization of gut-derived T cells in experimental and
ulcerative colitis.
AB - BACKGROUND: In the respiratory mucosa, interleukin (IL)-33, has been shown to
enhance T helper 2 (TH2)-type responses through the master regulatory gene GATA
3. IL-33 is upregulated in ulcerative colitis (UC), and the aim was to assess if
IL-33 holds a similar key position in the shaping of the immune response in
experimental colitis (piroxicam-accelerated colitis (PAC) in IL-10 (-/-) mice,
dextran sodium sulfate (DSS) model) and UC. METHODS: Colonic IL-33 expression was
determined in UC (8 active UC, 8 quiescent UC, and 7 controls) and experimental
colitis. Mesenteric lymph node (MesLN) T cells were isolated from PAC IL-10 (-/-)
mice and stimulated with IL-33. RESULTS: The colonic IL-33 expression was
significantly upregulated all forms of colitis (P < 0.01) and correlated with
disease severity score and inflammation (P < 0.001), and with GATA-3 expression
levels (P < 0.01); no correlation with the TH1-specific T-bet expression was
observed. MesLN T cells stimulated with IL-33 had increased GATA-3 expression,
and showed an IL-33 dose-dependent increase in secreted TH2-type cytokines,
whereas this effect was abolished by blocking IL-33 signaling. The non-TH2-type
cytokine IL-17 was upregulated by IL-33 but in a T cell receptor dependent
manner, as opposed to TH2-type cytokines, which required only IL-33 stimulation.
CONCLUSIONS: The study demonstrates that intestinal IL-33 is capable of inducing
GATA-3 in mucosal T cells, and suggests that IL-33 is a key mediator of
pathological TH2 and non-TH2-type responses in intestinal inflammation. Blocking
IL-33 signaling could be a feasible option in the treatment of UC.
PMID- 25112702
TI - Declining trends in alcohol consumption among Swedish youth-does the theory of
collectivity of drinking cultures apply?
AB - AIMS: To analyse trends in alcohol consumption among young people in Sweden
between 2004 and 2012, to test whether the theory of collectivity of drinking
cultures is valid for a population of young people and to investigate the impact
of an increasing proportion of abstainers on the overall per capita trends.
METHODS: Data were drawn from an annual survey of a nationally representative
sample of students in year 11 (17-18 years old). The data covered 9 years and the
total sample comprised 36,141 students. Changes in the overall per capita
consumption were tested using linear regression on log-transformed data, and
changes in abstention rates were tested using logistic regression. The analyses
were then continued by calculating average consumption in deciles. RESULTS:
Alcohol consumption among year 11 students declined significantly among both boys
and girls between 2004 and 2012. These changes were reflected at all levels of
consumption, and the same results were found when abstainers were excluded from
the analyses. The increasing proportion of abstainers had a minimal effect on the
overall decline in consumption; rather, this was driven by a decline in
consumption among the heaviest drinkers. CONCLUSION: The theory of collectivity
of drinking cultures seems valid for understanding changes in alcohol consumption
among Swedish year 11 students. No support was found for a polarization of
alcohol consumption in this nationally representative sample.
PMID- 25112703
TI - Comment on Rezen et al. Expression changes in human skeletal muscle miRNAs
following 10 days of bed rest in young healthy males. Acta Physiol 2014; 210: 655
666.
PMID- 25112701
TI - Overexpression and gene amplification of EGFR, HER2, and HER3 in biliary tract
carcinomas, and the possibility for therapy with the HER2-targeting antibody
pertuzumab.
AB - BACKGROUND: Pertuzumab is a humanized monoclonal antibody that binds to HER2 at
an epitope that prevents HER2 from dimerizing with ligand-activated HER-family
receptors. To assess the potential of pertuzumab as a new therapy, the expression
status of HER family members was determined in biliary tract carcinoma (BTC), and
the antitumor activity of pertuzumab was investigated by assessing the inhibition
of BTC cell growth. METHODS: The expression status of HER family members in 113
archival specimens of BTC was analyzed by using immunohistochemistry and
fluorescence in situ hybridization. Using ten BTC cell lines, heregulin-alpha
(HRG-alpha) stimulated cell proliferation and its inhibition by pertuzumab was
tested in vitro. The phosphorylated HER family proteins and their respective
downstream molecules were analyzed. In vivo antitumor activity of pertuzumab was
evaluated in a xenograft model. RESULTS: Protein overexpression of HER2 and/or
HER3 was observed in 23-34 % of the specimens and gene amplification in 17-27 %.
Seven of the ten cell lines showed HER2 and/or HER3 protein overexpression and
gene amplification, and HRG-alpha stimulated cell proliferation was observed in
four of the ten cell lines. In a BTC cell line co-overexpressing HER2 and HER3,
pertuzumab potently inhibited the HRG-alpha stimulated cell proliferation in a
dose-dependent manner, and completely blocked the phosphorylation of HER3.
Suppression of downstream pathway molecules including p-AKT was also observed.
Pertuzumab inhibited the in vivo growth of subcutaneous tumors, and increased the
number of apoptotic cancer cells. CONCLUSIONS: Pertuzumab exerts potent antitumor
activity in BTC cells co-overexpressing HER2 and HER3. Pertuzumab provides a new
therapeutic option against BTC.
PMID- 25112704
TI - Endocrine disrupting potential of fipronil and its metabolite in reporter gene
assays.
AB - There is a rising concern about the ecological safety and potential health risks
caused by pesticides that are commonly present in the environment. Previous
studies have shown that metabolites of pesticides sometimes possess more potent
endocrine activity than the parent compounds. However very little efforts had
been devoted to evaluate the environmental risks of pesticide metabolites. In the
present study, we evaluated the agonistic and antagonistic activities of fipronil
and its metabolite, fipronil sulfone, and compared by in vitro reporter gene
assays using CHO-K1 cells. For estrogenic and antiestrogenic activities, both
fipronil and fipronil sulfone showed no agonistic activities but exhibited the
similarly antagonistic activities via estrogen receptor alpha (ERalpha), with the
RIC20 of 6.4 * 10(-7)M and 9.8 * 10(-7)M, respectively. In the thyroid hormone
receptor (TR) assay, only fipronil sulfone showed anti-thyroid hormone activity
with the RIC20 of 8.2 * 10(-7)M. Furthermore, molecular docking was employed to
support the results in TR assay with lower MolDock score for fipronil sulfone.
Data provided here suggested that it is of great significance to study the
endocrine-disrupting effects of pesticide's metabolites, especially those with
persistence in environment and high toxicity to non-targeted organisms.
PMID- 25112705
TI - AChE inhibition: one dominant factor for swimming behavior changes of Daphnia
magna under DDVP exposure.
AB - As a key enzyme that hydrolyzes the neurotransmitter acetylcholine in cholinergic
synapses of both vertebrates and invertebrates, acetylcholinesterase (AChE) is
strongly inhibited by organophosphates. AChE inhibition may induce the decrease
of swimming ability. According to previous research, swimming behavior of
different aquatic organisms could be affected by different chemicals, and there
is a shortage of research on direct correlation analysis between swimming
behavior and biochemical indicators. Therefore, swimming behavior and whole-body
AChE activity of Daphnia magna under dichlorvos (DDVP) exposure were identified
in order to clarify the relationship between behavioral responses and AChE
inhibition in this study. In the beginning, AChE activity was similar in all
treatments with the control. During all exposures, the tendency of AChE activity
inhibition was the same as the behavioral responses of D. magna. The AChE
activity of individuals without movement would decrease to about zero in several
minutes. The correlation analysis between swimming behavior of D. magna and AChE
activity showed that the stepwise behavioral response was mainly decided by AChE
activity. All of these results suggested that the toxicity characteristics of
DDVP as an inhibitor of AChE on the swimming behavior of organisms were the same,
and the AChE activity inhibition could induce loss of the nerve conduction
ability, causing hyperactivity, loss of coordination, convulsions, paralysis and
other kinds of behavioral changes, which was illustrated by the stepwise
behavioral responses under different environmental stresses.
PMID- 25112707
TI - NHS staff will treat civilians injured in Gaza.
PMID- 25112706
TI - Sex-specific effects of long-term exposure to bisphenol-A on anxiety- and
depression-like behaviors in adult mice.
AB - Humans are routinely exposed to low levels of bisphenol A (BPA), an environmental
endocrine disruptor, which is widely used in the production of polycarbonate
plastics. The effects of perinatal exposure to BPA have been shown to affect
various aspects of social behaviors such as anxiety and depression in adult
offspring. Because sex hormones play a critical role in neurobehavior in
adulthood, it is possible that long-term exposure to BPA has widespread effects
on these emotional behaviors in adulthood. In the present study, adult mice were
exposed to BPA at dosages of 0.04, 0.4, 4, 40 mg kg(-1)d(-1) for 12 weeks. A
behavioral assay was performed using the open field test (OFT), mirrored maze,
the elevated plus maze (EPM), and the forced swim task. The results showed that,
after exposure to BPA at 0.4-40 mg kg(-1)d(-1), the number of open arm entries
and the time spent in them in the elevated plus maze task were reduced in males
but increased in females, and thus eliminating or reversing sex differences in
these behaviors. BPA at 0.04-40 mg kg(-1)d(-1) increased the immobility of male
mice in the forced swimming test. Furthermore, BPA (0.4-40 mg kg(-1)d(-1))
significantly decreased brain level of testosterone in males, but no significant
influence was found in serum and the brain levels of estradiol in females.
Western blot analysis further indicated that BPA at 0.4, 4, or 40 mg kg(-1)d(-1)
significantly down-regulated the protein level of estrogen receptor beta (ERbeta)
in the hippocampus of the adult males but not females, and inhibited the protein
level of GABA(A)alpha2 receptor in hippocampus of males but promoted that of
females. These results suggest that long-term exposure to BPA sex specifically
affects anxiety- and depression-like behaviors in adult mice. Changes in the
levels of GABA(A)alpha2 receptor and ERbeta proteins of hippocampus might be
associated with BPA-induced changes in these emotional behaviors.
PMID- 25112708
TI - Proton pump inhibitor-responsive oesophageal eosinophilia correlates with
downregulation of eotaxin-3 and Th2 cytokines overexpression.
AB - BACKGROUND: The molecular basis and effects of proton pump inhibitor (PPI)
therapy on PPI-responsive oesophageal eosinophilia (PPI-REE) and eosinophilic
oesophagitis (EoE) remain unknown. AIM: To compare symptom-histological and
cytokine gene expression in PPI-REE and EoE patients, at baseline and after
specific treatment. METHODS: In consecutive adult patients with an EoE phenotype
(dysphagia/food impaction, typical endoscopic findings and > 15 eos/HPF), gene
expression of eotaxin-3, IL-13, and IL-5 were determined in distal and proximal
oesophagus, at baseline and after omeprazole 40 mg b.d. for 8 weeks. PPI-REE was
defined by clinicohistological response. PPI nonresponders (EoE) were offered
treatment with topical steroids. RESULTS: Fifty three patients were re-evaluated
on PPI therapy. 23 patients (43%) had PPI-REE and 30 patients (57%) had EoE. At
baseline, eotaxin-3/IL-13/IL-5 gene expression was indistinguishable between EoE
and PPI-REE, excepting increased IL-5 expression in proximal oesophagus (12.54
vs. 57, P = 0.029). PPI therapy significantly decreased eotaxin-3/IL-13 in PPI
REE, at both oesophageal sites (P <= 0.008), and IL-5 in distal (P = 0.016), but
not in proximal oesophagus. Patients with steroid-responsive EoE also showed a
significant decrease in eotaxin-3/IL-5 expression at both oesophageal sites. In
EoE patients, initial PPI trial significantly decreased distal oesophageal
eosinophilia (63.78 to 41.79 eos/HPF, P = 0.025) and led to symptom remission in
16%, but did not influence Th2 markers. CONCLUSIONS: Baseline cytokine gene
expression in PPI-REE was nearly indistinguishable from EoE. PPI therapy
significantly downregulated oesophageal eotaxin-3/Th2-cytokine gene expression in
PPI-REE, similarly to that seen in steroid-responsive EoE. A subset of EoE
patients showed clinicohistological improvement on PPI therapy.
PMID- 25112709
TI - Prognostic implication of intratumoral metabolic heterogeneity in invasive ductal
carcinoma of the breast.
AB - BACKGROUND: The purpose of this study was to evaluate the prognostic implication
of findings of intratumoral metabolic heterogeneity on pretreatment (18)F-FDG
PET/CT scans in patients with invasive ductal carcinoma (IDC) of the breast.
METHODS: One hundred and twenty-three female IDC patients who underwent
pretreatment 18F-fluorodeoxyglucose positron-emission tomography/computed
tomography ((18)F-FDG PET/CT) scans were retrospectively evaluated in this study.
The heterogeneity factor (HF) defined as the derivative (dV/dT) of a volume
threshold function from 40% to 80%, was computed for each primary tumor. Other
metabolic PET parameters (maximum standardized uptake value [SUVmax], metabolic
tumor volume [MTV], and total lesion glycolysis [TLG]) were measured. The HF was
compared with clinicopathologic factors and other PET parameters. Univariate and
multivariate analyses for the overall survival (OS) were performed. RESULTS: The
HF ranged from 0.02 to 6.72 (mean, 0.35 +/- 0.82) and significantly correlated
with MTV (r = 0.955; p < 0.0001) and TLG (r = 0.354; p = 0.0001). The HF was
significantly higher (implying more heterogeneity) in tumors with higher T and N
stages. The optimal cut-off values for the OS determined using a receiver
operating characteristic (ROC) curve were 0.34 for the HF, 5.6 for SUVmax, 8.55
cm(3) for MTV, and 14.43 for TLG. The OS rate among the 123 patients was 86.2%. T
stage (1, 2 vs. 3, 4), N stage (0, 1 vs. 2, 3), M stage (0 vs. 1), ER status (+
vs. -), SUVmax (<= 5.6 vs. > 5.6), MTV (<= 8.55 cm(3) vs. > 8.55 cm(3)), TLG (<=
14.43 vs. > 14.43), and HF (< 0.34 vs. >= 0.34) affected the OS on univariate
analysis. After adjustment for the effects of TNM stage and ER status, the HF and
MTV were significant predictors of OS. Among the PET parameters, the best
prognostic factor for OS was the HF. CONCLUSIONS: Intratumoral metabolic
heterogeneity correlated closely with the MTV and significantly affected the OS
in IDC patients. The HF may act as a robust surrogate marker for the prediction
of OS in IDC patients.
PMID- 25112711
TI - Nociceptive neurons regulate innate and adaptive immunity and neuropathic pain
through MyD88 adapter.
PMID- 25112712
TI - An ingredient for the elixir of youth.
AB - Emerging evidence indicates that there are factors within the blood of young
animals that have the ability to restore youthful characteristics to a number of
organ systems in older animals. Growth/differentiation factor 11 (GDF11) is the
first of such factors to be identified, and two new studies demonstrate that this
"factor of youth" rejuvenates stem cells found in the skeletal muscle and brain
of aged mice.
PMID- 25112714
TI - FNDC5 could be regulated by leptin in adipose tissue.
AB - INTRODUCTION: Irisin activates the thermogenic function in adipose tissues.
However, little is known on the association between human irisin and different
cardiometabolic risk factors. We analyse the influence of morbid obesity on
irisin levels and its relation with leptin and different cardiovascular risk
factors. MATERIAL AND METHODS: We measured the serum irisin level and the
fibronectin type III domain containing 5 (FNDC5) expression in adipose tissue
from 33 morbidly obese subjects and 12 nonobese subjects. We also studied the
effect of leptin on FNDC5 expression. RESULTS: Serum irisin was higher in the
nonobese subjects than in morbidly obese subjects, both before (P = 0.043) and
after bariatric surgery (P = 0.042). The variable that best explained the serum
irisin levels in a multiple linear regression model was the waist-to-hip ratio
(WHR) (R(2) = 0.201) (Beta = -0.357, P = 0.046). Those morbidly obese subjects
with android-type obesity had lower serum irisin levels than those with gynecoid
type obesity, both before (P = 0.027) and after bariatric surgery (P = 0.006).
Only the percentage change in WHR was associated with serum irisin levels after
bariatric surgery (r = -0.529, P = 0.005). FNDC5 expression levels in
subcutaneous adipose tissue (SAT) were higher in the nonobese than in the
morbidly obese subjects (P = 0.042). In SAT explants from nonobese subjects,
leptin (20 and 150 ng/mL) produced a decrease in FNDC5 expression (P = 0.009 and
P = 0.037, respectively). CONCLUSIONS: We showed decreased serum irisin levels in
morbidly obese subjects, related mainly to WHR. FNDC5 expression could be
regulated by leptin.
PMID- 25112715
TI - Structurally enhanced incremental neural learning for image classification with
subgraph extraction.
AB - In this paper, a structurally enhanced incremental neural learning technique is
proposed to learn a discriminative codebook representation of images for
effective image classification applications. In order to accommodate the
relationships such as structures and distributions among visual words into the
codebook learning process, we develop an online codebook graph learning method
based on a novel structurally enhanced incremental learning technique, called as
"visualization-induced self-organized incremental neural network (ViSOINN)". The
hidden structural information in the images is embedded into the graph
representation evolving dynamically with the adaptive and competitive learning
mechanism. Afterwards, image features can be coded using a sub-graph extraction
process based on the learned codebook graph, and a classifier is subsequently
used to complete the image classification task. Compared with other codebook
learning algorithms originated from the classical Bag-of-Features (BoF) model,
ViSOINN holds the following advantages: (1) it learns codebook efficiently and
effectively from a small training set; (2) it models the relationships among
visual words in metric scaling fashion, so preserving high discriminative power;
(3) it automatically learns the codebook without a fixed pre-defined size; and
(4) it enhances and preserves better the structure of the data. These
characteristics help to improve image classification performance and make it more
suitable for handling large-scale image classification tasks. Experimental
results on the widely used Caltech-101 and Caltech-256 benchmark datasets
demonstrate that ViSOINN achieves markedly improved performance and reduces the
computational cost considerably.
PMID- 25112713
TI - Massive glycosaminoglycan-dependent entry of Trp-containing cell-penetrating
peptides induced by exogenous sphingomyelinase or cholesterol depletion.
AB - Among non-invasive cell delivery strategies, cell-penetrating peptide (CPP)
vectors represent interesting new tools. To get fundamental knowledge about the
still debated internalisation mechanisms of these peptides, we modified the
membrane content of cells, typically by hydrolysis of sphingomyelin or depletion
of cholesterol from the membrane outer leaflet. We quantified and visualised the
effect of these viable cell surface treatments on the internalisation efficiency
of different CPPs, among which the most studied Tat, R9, penetratin and
analogues, that all carry the N-terminal biotin-Gly4 tag cargo. Under these cell
membrane treatments, only penetratin and R6W3 underwent a massive
glycosaminoglycan (GAG)-dependent entry in cells. Internalisation of the other
peptides was only slightly increased, similarly in the absence or the presence of
GAGs for R9, and only in the presence of GAGs for Tat and R6L3. Ceramide
formation (or cholesterol depletion) is known to lead to the reorganisation of
membrane lipid domains into larger platforms, which can serve as a trap and
cluster receptors. These results show that GAG clustering, enhanced by formation
of ceramide, is efficiently exploited by penetratin and R6W3, which contains Trp
residues in their sequence but not Tat, R9 and R6L3. Hence, these data shed new
lights on the differences in the internalisation mechanism and pathway of these
peptides that are widely used in delivery of cargo molecules.
PMID- 25112716
TI - Event-related complexity analysis and its application in the detection of facial
attractiveness.
AB - In this study, an event-related complexity (ERC) analysis method is proposed and
used to explore the neural correlates of facial attractiveness detection in the
context of a cognitive experiment. The ERC method gives a quantitative index for
measuring the diverse brain activation properties that represent the neural
correlates of event-related responses. This analysis reveals distinct effects of
facial attractiveness processing and also provides further information that could
not have been achieved from event-related potential alone.
PMID- 25112717
TI - The role of the SST-thermocline relationship in Indian Ocean Dipole skewness and
its response to global warming.
AB - A positive Indian Ocean Dipole (IOD) tends to have stronger cold sea surface
temperature anomalies (SSTAs) over the eastern Indian Ocean with greater impacts
than warm SSTAs that occur during its negative phase. Two feedbacks have been
suggested as the cause of positive IOD skewness, a positive Bjerknes feedback and
a negative SST-cloud-radiation (SCR) feedback, but their relative importance is
debated. Using inter-model statistics, we show that the most important process
for IOD skewness is an asymmetry in the thermocline feedback, whereby SSTAs
respond to thermocline depth anomalies more strongly during the positive phase
than negative phase. This asymmetric thermocline feedback drives IOD skewness
despite positive IODs receiving greater damping from the SCR feedback. In
response to global warming, although the thermocline feedback strengthens, its
asymmetry between positive and negative IODs weakens. This behaviour change
explains the reduction in IOD skewness that many models display under global
warming.
PMID- 25112718
TI - Histamine impairs midbrain dopaminergic development in vivo by activating
histamine type 1 receptors.
AB - BACKGROUND: Histamine (HA) regulates the sleep-wake cycle, synaptic plasticity
and memory in adult mammals. Dopaminergic specification in the embryonic ventral
midbrain (VM) coincides with increased HA brain levels. To study the effect of HA
receptor stimulation on dopamine neuron generation, we administered HA to
dopamine progenitors, both in vitro and in vivo. RESULTS: Cultured embryonic day
12 (E12) VM neural stem/progenitor cells expressed transcripts for HA receptors
H1R, H2R and H3R. These undifferentiated progenitors increased intracellular
calcium upon HA addition. In HA-treated cultures, dopamine neurons significantly
decreased after activation of H1R. We performed intrauterine injections in the
developing VM to investigate HA effects in vivo. HA administration to E12 rat
embryos notably reduced VM Tyrosine Hydroxylase (TH) staining 2 days later,
without affecting GABA neurons in the midbrain, or serotonin neurons in the mid
hindbrain boundary. qRT-PCR and Western blot analyses confirmed that several
markers important for the generation and maintenance of dopaminergic lineage such
as TH, Lmx1a and Lmx1b were significantly diminished. To identify the cell type
susceptible to HA action, we injected embryos of different developmental stages,
and found that neural progenitors (E10 and E12) were responsive, whereas
differentiated dopaminergic neurons (E14 and E16) were not susceptible to HA
actions. Proliferation was significantly diminished, whereas neuronal death was
not increased in the VM after HA administration. We injected H1R or H2R
antagonists to identify the receptor responsible for the detrimental effect of HA
on dopaminergic lineage and found that activation of H1R was required.
CONCLUSION: These results reveal a novel action of HA affecting dopaminergic
lineage during VM development.
PMID- 25112720
TI - Post-fracture pharmacotherapy for women with osteoporotic fracture: analysis of a
managed care population in the USA.
AB - Pharmacologic therapy is recommended to reduce future fracture risk. We examined
osteoporosis medications dispensed to older women after first fracture. Only 23 %
received therapy during the first year post-fracture. Prior osteoporosis therapy,
a prior osteoporosis diagnosis, and older age were good predictors of post
fracture osteoporosis therapy. INTRODUCTION: Pharmacologic therapy is recommended
after osteoporotic fracture to reduce future fracture risk. The objective of this
retrospective study was to examine osteoporosis therapy dispensed to women post
fracture. METHODS: We identified women >=50 years old in a large administrative
claims database from 2003 to mid-2012 who were continuously enrolled 2 years
before (baseline) and 1 year after first osteoporotic fracture. Exclusions were
Paget's disease or malignant neoplasm. Pre- and post-fracture osteoporosis
therapies (oral and parenteral) were assessed overall and by fracture site.
RESULTS: A total of 47,171 women of mean (SD) age of 63 (10) years were eligible;
fractures included 8 % hip, 17 % vertebral, 73 % non-hip/non-vertebral, and 3 %
multiple fracture sites. Only 18 % received osteoporosis therapy within 90 days
and 23 % within 1 year post-fracture. Overall, 19 % of women had a prior
osteoporosis diagnosis; 20 % had received osteoporosis therapy during baseline.
Of 37,649 (80 %) women without baseline therapy, only 9 % initiated pharmacologic
therapy within 1 year. The adjusted odds ratio (OR) of therapy within 1 year post
fracture was significantly greater for women who had received baseline
osteoporosis therapy (versus none) and who had vertebral (OR 12.7, 95 %
confidence interval (CI) 11.2-14.5), hip (15.2, 12.5-18.7), or non-hip/non
vertebral fracture (34.4, 31.7-37.3). Other significant predictors included pre
fracture osteoporosis diagnosis (1.6, 1.4-1.7) and older age (OR range, 1.3-1.7).
Treatment adherence was significantly better among women with baseline
osteoporosis diagnosis. CONCLUSIONS: The substantial post-fracture treatment gap
represents an important unmet need for women with osteoporotic fractures.
Fracture liaison or adherence programs could lead to improved post-fracture
treatment rates.
PMID- 25112721
TI - Effect of education intervention on the quality and long-term outcomes of root
canal treatment in general practice.
AB - AIM: To compare the technical quality and long-term outcomes of root canal
treatment by general practitioners of a Swedish Public Dental Service, before and
after an endodontic education including Ni-Ti rotary technique (NiTiR).
METHODOLOGY: A random sample was compiled, comprising one root filled tooth from
each of 830 patients, treated by 69 general practitioners participating in the
education: 414 teeth root filled in 2002, pre-education, using primarily
stainless steel instrumentation and filling by lateral compaction, and 416 teeth
root filled post-education (2005), using mainly NiTiR and single-cone obturation.
Follow-up radiographs taken in 2009 were evaluated alongside immediate post
filling radiographs from 2002 to 2005. The density and length of the root
fillings were registered. Periapical status was assessed by the Periapical Index
(PAI), using two definitions of disease: apical periodontitis (AP) (PAI 3 + 4 +
5) and definite AP (PAI 4 + 5). Tooth survival was registered. Root fillings pre-
and post-education were compared using chi-square and Fisher's exact tests. Crude
extraction rates per 100 years were calculated for comparison of tooth survival.
Explanatory variables (type of tooth, root filling quality, periapical status,
marginal bone loss, type and quality of coronal restoration) in relation to the
dependent variable (AP at follow-up) were analysed by multivariable logistic
regression. RESULTS: Follow-up data were available for 229 (55%) of teeth treated
pre- and 288 (69%) treated post-education: both tooth survival (P < 0.001) and
root filling quality were significantly higher (P < 0.001) in the latter.
However, there was no corresponding improvement in periapical status. Both pre-
and post-education, root fillings with definite AP on completion of treatment had
significantly higher odds of AP or definite AP at follow-up. For teeth treated
post-education, inadequate root filling quality was significantly associated with
AP at follow-up. CONCLUSIONS: Despite a higher tooth survival rate and a
significant improvement in technical quality of root fillings after the
education, there was no corresponding improvement in periapical status.
PMID- 25112722
TI - Patient-reported outcomes in Crohn's disease: does race matter?
PMID- 25112719
TI - Icariin may benefit the mesenchymal stem cells of patients with steroid
associated osteonecrosis by ABCB1-promoter demethylation: a preliminary study.
AB - In this study, we found out a previously undefined function of icariin which
restored the dynamic balance between osteogenic and adipogenic differentiation of
mesenchymal stem cells (MSCs) in patients with osteonecrosis of femoral head
(ONFH) via ABCB1-promoter demethylation. These findings provided important
information regarding potential implication of icariin targeting epigenetic
changes for the treatment of steroid -associated ONFH. INTRODUCTION: Here, we
investigated whether icariin can also exert a beneficial role in the reactivation
of MSCs in the patients with steroid-associated ONFH via ABCB1-promoter
demethylation. METHODS: Bone marrow was collected from the proximal femur in
patients with steroid-associated ONFH (n = 20) and patients with new femoral neck
fractures (n = 22), and then MSCs were isolated. We investigated cell viability,
intracellular reactive oxygen species (ROS) level, mitochondrial membrane
potential (MMP), P-glycoprotein (P-gp) activity, the transcript levels of ABCB1
and oxidative stress-related genes, methylation extent at CpG islands of ABCB1
promoter, and osteogenic and adipogenic differentiation ability of MSCs from the
femoral neck fractures group and from the steroid-associated ONFH group treated
with or without icariin. RESULTS: We observed that MSCs from the steroid
associated ONFH group showed reduced proliferation ability, elevated ROS level,
depressed MMP, weakened osteogenesis, and enhanced adipogenesis while low P-gp
activity, transcription level of ABCB1, and oxidative stress-related genes as
well as aberrant CpG islands hypermethylation of ABCB1 were also noted in steroid
associated ONFH group. Treatment with icariin obviously induced de novo P-gp
expression, decreased oxidative stress, and promoted osteogenesis. CONCLUSION:
Icariin may be a potential drug targeting epigenetic changes for the treatment of
steroid-associated ONFH.
PMID- 25112724
TI - Visualizing oil displacement with foam in a microfluidic device with permeability
contrast.
AB - Foam mobility control and novel oil displacement mechanisms were observed in a
microfluidic device representing a porous media system with layered permeability.
Foam was pre-generated using a flow-focusing microfluidic device and injected
into an oil-wet, oil-saturated 2-D PDMS microfluidic device. The device is
designed with a central fracture flanked by high-permeability and low
permeability zones stratified in the direction of injection. A 1 : 1, 1% blend of
alpha olefin sulfonate 14-16 (AOS) and lauryl betaine (LB) surfactants produced
stable foam in the presence of paraffin oil. The oil saturation and pressure drop
across the microfluidic device were measured as a function of time and the
injected pore volume, indicating an increase in apparent viscosity for foam with
an accompanying decrease in oil saturation. In contrast to the control
experiments, foam was shown to more effectively mobilize trapped oil by
increasing the flow resistance in the fracture and high-permeability zones and by
diverting the surfactant solution into adjacent low-permeability zones. The foam
was observed to separate into gas-rich and aqueous-rich phases depending on
matrix permeability, suggesting that it is not appropriate to treat foam as a
homogeneous dispersion of gas and liquid.
PMID- 25112723
TI - The histological quality and adequacy of diminutive colorectal polyps resected
using jumbo versus hot biopsy forceps.
AB - BACKGROUND: Polypectomy with jumbo forceps (JF) and polypectomy with hot biopsy
forceps (HBF) are still widely used techniques for removal of diminutive
colorectal polyps (DCPs). JF may be more effective for the removal of DCPs
because of their larger size. AIM: To evaluate the histological quality and
adequacy of DCPs resected using JF compared with HBF. METHODS: One hundred and
seventy-nine patients with 237 DCPs were included in this study. DCPs were
removed using either JP or HBF. RESULTS: The tissue architecture was good in 29.9
% of the HBF group, in comparison with 90 % of the JF group (p < 0.001). No
cautery damage or crash artifact was observed in 93.3 % of JF group and in 8.5 %
of HBF group (p < 0.001). Moreover, there were statistically significant
differences between the groups with regard to the high level of cautery damage or
crush artifact (p < 0.001). The overall diagnostic quality of the specimens
removed using JF was significantly better than that of the specimens removed by
HBF (96 vs. 80 %, respectively, p < 0.001). There were statistically significant
inverse associations between cautery damage or crush artifact and overall
diagnostic quality of HBF and JF (r = -0.373, p < 0.001; r = -0.382, p < 0.001,
respectively). Surgical margins were determined as negative in 87.5 % of the JF
group and in 76.1 % of the HBF group (p = 0.022). A total of 80.8 % of the JF
specimens and 30.8 % of the HBF specimens were well evaluated for two lateral and
deep surgical margins (p < 0.001). CONCLUSION: JF was superior to HBF for
histopathological interpretation and eradication of DCPs.
PMID- 25112727
TI - Synthesis and evaluation of novel analogues of ripostatins.
AB - Ripostatins are polyene macrolactones isolated from the myxobacterium Sorangium
cellulosum. They exhibit antibiotic activity by inhibiting bacterial RNA
polymerase (RNAP) through a binding site and mechanism that are different from
those of current antibacterial drugs. Thus, the ripostatins serve as starting
points for the development of new anti-infective agents with a novel mode of
action. In this work, several derivatives of ripostatins were produced. 15
Desoxyripostatin A was synthesized by using a one-pot carboalumination/cross
coupling. 5,6-Dihydroripostatin A was constructed by utilizing an intramolecular
Suzuki cross-coupling macrolactonization approach. 14,14'-Difluororipostatin A
and both epimeric 14,14'-difluororipostatins B were synthesized by using a
Reformatsky type aldol addition of a haloketone, Stille cross-coupling, and ring
closing metathesis. The RNAP-inhibitory and antibacterial activities are
presented. Structure-activity relationships indicate that the monocyclic keto-ol
form of ripostatin A is the active form of ripostatin A, that the ripostatin C5
C6 unsaturation is important for activity, and that C14 geminal difluorination of
ripostatin B results in no loss of activity.
PMID- 25112731
TI - Female fetus is associated with greater maternal insulin resistance in pregnancy.
AB - AIM: To explore the hypothesis that female fetus is associated with greater
maternal insulin resistance during pregnancy. METHODS: In a singleton pregnancy
cohort study (n = 299), we compared maternal insulin resistance according to
fetal sex, based on plasma biomarkers from a 50-g 1-h oral glucose tolerance test
at 24-28 weeks gestation. The primary outcome was plasma glucose-to-insulin
ratio. Other outcomes included plasma proinsulin-to-insulin ratio, and insulin,
proinsulin, leptin, adiponectin and insulin-like growth factor I and II
concentrations. RESULTS: After adjusting for maternal race, age, parity,
education, pre-pregnancy BMI, smoking and alcohol use, history of gestational
diabetes, and gestational age at blood sampling, plasma insulin concentrations
were significantly higher (mean +/- sd: 66.4 +/- 50.5 vs. 51.0 +/- 46.1 mU/l;
adjusted P = 0.001), and glucose-to-insulin ratios significantly lower (2.60 +/-
2.03 vs. 3.77 +/- 4.98 mg/dl/mU/l; adjusted P = 0.002) in women bearing a female
vs those bearing a male fetus, despite similar glucose levels (116.4 +/- 27.2 vs.
117.0 +/- 31.9 mg/dl; adjusted P = 0.92).There were no significant differences in
proinsulin-to-insulin ratios, or leptin, adiponectin, insulin-like growth factor
I and insulin-like growth factor II concentrations by fetal sex. CONCLUSION:
Female fetus may be associated with greater maternal insulin resistance during
pregnancy.
PMID- 25112726
TI - DNA damage accumulation and repair defects in acute myeloid leukemia:
implications for pathogenesis, disease progression, and chemotherapy resistance.
AB - DNA damage repair mechanisms are vital to maintain genomic integrity. Mutations
in genes involved in the DNA damage response (DDR) can increase the risk of
developing cancer. In recent years, a variety of polymorphisms in DDR genes have
been associated with increased risk of developing acute myeloid leukemia (AML) or
of disease relapse. Moreover, a growing body of literature has indicated that
epigenetic silencing of DDR genes could contribute to the leukemogenic process.
In addition, a variety of AML oncogenes have been shown to induce replication and
oxidative stress leading to accumulation of DNA damage, which affects the balance
between proliferation and differentiation. Conversely, upregulation of DDR genes
can provide AML cells with escape mechanisms to the DDR anticancer barrier and
induce chemotherapy resistance. The current review summarizes the DDR pathways in
the context of AML and describes how aberrant DNA damage response can affect AML
pathogenesis, disease progression, and resistance to standard chemotherapy, and
how defects in DDR pathways may provide a new avenue for personalized therapeutic
strategies in AML.
PMID- 25112730
TI - Cross-sectional associations between air pollution and chronic bronchitis: an
ESCAPE meta-analysis across five cohorts.
AB - BACKGROUND: This study aimed to assess associations of outdoor air pollution on
prevalence of chronic bronchitis symptoms in adults in five cohort studies
(Asthma-E3N, ECRHS, NSHD, SALIA, SAPALDIA) participating in the European Study of
Cohorts for Air Pollution Effects (ESCAPE) project. METHODS: Annual average
particulate matter (PM(10), PM(2.5), PM(absorbance), PM(coarse)), NO(2), nitrogen
oxides (NO(x)) and road traffic measures modelled from ESCAPE measurement
campaigns 2008-2011 were assigned to home address at most recent assessments
(1998-2011). Symptoms examined were chronic bronchitis (cough and phlegm for >=3
months of the year for >=2 years), chronic cough (with/without phlegm) and
chronic phlegm (with/without cough). Cohort-specific cross-sectional
multivariable logistic regression analyses were conducted using common confounder
sets (age, sex, smoking, interview season, education), followed by meta-analysis.
RESULTS: 15 279 and 10 537 participants respectively were included in the main
NO(2) and PM analyses at assessments in 1998-2011. Overall, there were no
statistically significant associations with any air pollutant or traffic
exposure. Sensitivity analyses including in asthmatics only, females only or
using back-extrapolated NO(2) and PM10 for assessments in 1985-2002 (ECRHS, NSHD,
SALIA, SAPALDIA) did not alter conclusions. In never-smokers, all associations
were positive, but reached statistical significance only for chronic phlegm with
PM(coarse) OR 1.31 (1.05 to 1.64) per 5 ug/m(3) increase and PM(10) with similar
effect size. Sensitivity analyses of older cohorts showed increased risk of
chronic cough with PM(2.5abs) (black carbon) exposures. CONCLUSIONS: Results do
not show consistent associations between chronic bronchitis symptoms and current
traffic-related air pollution in adult European populations.
PMID- 25112733
TI - First discovery of Quercus feeding Nepticulidae (Lepidoptera) in Central America.
AB - Despite the high taxonomic diversity of oaks in Mexico and Central America, no
Quercus feeding Nepticulidae have ever been recorded from the region. Here, we
present seven species whose larvae are leaf-miners of Quercus (section Lobatae)
in Guatemala. Except Stigmella nigriverticella (Chambers 1875), which was
previously known from the United States, all other discovered species are new. We
describe and name five new species (Stigmella jaguari Remeikis & Stonis, sp.
nov., S. lauta Diskus & Stonis, sp. nov., S. sublauta Remeikis & Stonis, sp.
nov., S. aurifasciata Diskus & Stonis, sp. nov. and S. guatemalensis Diskus &
Stonis, sp. nov.); the remaining new species is described but left unnamed
because of lack of adults (i. e. moths and genitalia are described from developed
pupae). All seven treated species are illustrated with photographs of the leaf
mines, adults, and genitalia.
PMID- 25112732
TI - Lipocalin 2: a new mechanoresponding gene regulating bone homeostasis.
AB - Mechanical loading represents a crucial factor in the regulation of skeletal
homeostasis. Its reduction causes loss of bone mass, eventually leading to
osteoporosis. In a previous global transcriptome analysis performed in mouse
calvarial osteoblasts subjected to simulated microgravity, the most upregulated
gene compared to unit gravity condition was Lcn2, encoding the adipokine
Lipocalin 2 (LCN2), whose function in bone metabolism is poorly known. To
investigate the mechanoresponding properties of LCN2, we evaluated LCN2 levels in
sera of healthy volunteers subjected to bed rest, and found a significant time
dependent increase of this adipokine compared to time 0. We then evaluated the in
vivo LCN2 regulation in mice subjected to experimentally-induced mechanical
unloading by (1) tail suspension, (2) muscle paralysis by botulin toxin A
(Botox), or (3) genetically-induced muscular dystrophy (MDX mice), and observed
that Lcn2 expression was upregulated in the long bones of all of them, whereas
physical exercise counteracted this increase. Mechanistically, in primary
osteoblasts transfected with LCN2-expression-vector (OBs-Lcn2) we observed that
Runx2 and its downstream genes, Osterix and Alp, were transcriptionally
downregulated, and alkaline phosphatase (ALP) activity was less prominent versus
empty-vector transduced osteoblasts (OBs-empty). OBs-Lcn2 also exhibited an
increase of the Rankl/Opg ratio and IL-6 mRNA, suggesting that LCN2 could link
poor differentiation of osteoblasts to enhanced osteoclast stimulation. In fact,
incubation of purified mouse bone marrow mononuclear cells with conditioned media
from OBs-Lcn2 cultures, or their coculture with OBs-Lcn2, improved
osteoclastogenesis compared to OBs-empty, whereas treatment with recombinant LCN2
had no effect. In conclusion, our data indicate that LCN2 is a novel osteoblast
mechanoresponding gene and that its regulation could be central to the
pathological response of the bone tissue to low mechanical forces.
PMID- 25112735
TI - Redescription of five gnathiid species from Japan (Crustacea: Isopoda).
AB - Five gnathiid species from Japan are redescribed based on14 holotypes, their
paratypes, topotypes, and new materials. Observations of these specimens revealed
that Caecognathia kikuchii (Nunomura, 1992) should be transferred to genus
Elaphognathia and Caecognathia nasuta (Nunomura, 1992) to genus Gnathia.
Furthermore, Caecognathia amakusaensis Nunomura, 1992, C. saikaiensis Nunomura,
1992, Gnathia azumai Nunomura, 2012a, G. quadricephala Nunomura, 2012a, and G.
recticornata Nunomura, 2012a are considered to be junior synonyms of E. kikuchii.
Gnathia hirayamai Nunomura, 1992, G. nagasakiensis Nunomura, 2012a, G.
shijikiensis Nunomura, 2012a, and G. brevicephala Nunomura, 2012a are considered
to be junior synonyms of G. nasuta. Moreover, Gnathia sanrikuensis Nunomura, 1998
and G. mutsuensis Nunomura, 2004 are redescribed. Gnathia bungoensis Nunomura,
1982 is not completely redescribed because the key characteristics were lacking.
The geographical records of these species are provided.
PMID- 25112734
TI - A new species-group of Chrysura Dahlbom, 1845 (Hymenoptera: Chrysididae), with
description of Ch. baiocchii sp. nov. from Iran .
AB - Chrysura baiocchii Rosa sp. nov. is described from Iran. Diagnosis of the new
species-group Ch. baiocchii and discussions on Ch. radians group and Ch. genalis
subgroup are given.
PMID- 25112736
TI - New records of moth flies (Diptera: Psychodidae) from Croatia, with the
description of Berdeniella keroveci sp.nov.
AB - Berdeniella keroveci sp. nov. is described based on males collected in Croatia.
Current knowledge of the psychodid fauna of Croatia is reviewed and new records
of 16 species are presented. Short taxonomic notes on Pericoma pseudocalcilega
Krek, 1972, Pneumia balkanica (Krek, 1990), Pneumia mutua (Eaton, 1893), Clogmia
albipunctata (Williston, 1893) and Lepiseodina tristis (Meigen, 1810) are given.
In total, 33 species of Psychodidae are known to occur in Croatia.
PMID- 25112737
TI - A new species of Lixophaga Townsend (Diptera: Tachinidae) from Colombia, a
parasitoid of Neoleucinodes elegantalis (Guenee) (Lepidoptera: Crambidae).
AB - A new species of Lixophaga Townsend (Diptera: Tachinidae) from Colombia,
Lixophaga puscolulo Carrejo & Woodley, sp. nov., is described and illustrated. It
is a parasitoid of the tomato fruit borer, Neoleucinodes elegantalis (Guenee)
(Lepidoptera: Crambidae), an insect pest of Solanum quitoense Lam., in Colombia.
Aspects of its biology are briefly discussed.
PMID- 25112738
TI - New species of the genus Jacekaphorura (Collembola: Onychiuridae) from upper
reaches of Kolyma river (North-East of Russia).
AB - Two new species of the genus Jacekaphorura from the North-East of Russia, viz. J.
catherinae sp. nov. and J. furcata sp. nov., were described and illustrated. The
former species clearly differs from the only previously known species of the
genus by a high and variable number of dorsal pso, the latter can easily be
distinguished due to specific structure of furcal remnant. The generic diagnosis
and position within modern tribal subdivision of the Onychiurinae are discussed.
PMID- 25112739
TI - A new species of Elathous Reitter (Coleoptera: Elateridae) from Turkey.
AB - A new click-beetle species, Elathous serti, from Denizli and Isparta provinces of
Turkey is described. Photographs of the adults, drawings of the aedeagi, a
contrasting comparison table, a key to all Turkish Elathous species, a
distribution map, and a table of collecting months and collecting provinces of
all Turkish species are provided.
PMID- 25112740
TI - Munidopsis lauensis Baba & de Saint Laurent, 1992 (Decapoda, Anomura,
Munidopsidae), a newly recorded squat lobster from a cold seep in Taiwan.
AB - The squat lobster, Munidopsis lauensis Baba & de Saint Laurent, 1992, is recorded
from Taiwan for the first time. This species was previously known only from deep
sea hydrothermal vents in the South-West Pacific but it was now found at a deep
sea cold seep site off southwestern Taiwan. The identity of the Taiwanese
material is confirmed by comparison of sequences from the barcoding gene COI.
Munidopsis lauensis can be easily separated from other congeners in Taiwanese
waters by the eyes bearing a strong mesiodorsal spine and a small mesioventral
spine, smooth carapace, fingers of the cheliped distally spooned and fixed finger
without a denticulate carina on the distolateral margin. The discovery of this
species in Taiwan increases the Munidopsis fauna of the island to 38 species. A
color photograph and line drawings illustrating distinctive characters are
provided for the Taiwanese material.
PMID- 25112741
TI - First description of the female Ozyptila kansuensis (Tang, Song & Zhu, 1995),
comb. nov. (Araneae: Thomisidae) .
PMID- 25112742
TI - Four new leaf-mining Acalyptris species from Guatemala and Belize, with new data
on bionomics of Stigmella pruinosa (Lepidoptera: Nepticulidae).
AB - This paper describes four new species: Acalyptris basicornis Remeikis & Stonis,
sp. nov., A. peteni Diskus & Stonis, sp. nov., A. caribbicus Diskus & Stonis, sp.
nov. (host-plant: Lantana involucrata L., Verbenaceae), and A. statuarius Diskus
& Stonis, sp. nov. Another species, Stigmella pruinosa Puplesis & Robinson, is re
described, with new distribution records in Guatemala and with the first
documentation of leaf-mines on Guazuma ulmifolia Lam. (Malvaceae). All five
species are illustrated with photographs of the leaf-mines, adults, and
genitalia.
PMID- 25112743
TI - Cuapetes yapiensis sp. nov. (Crustacea: Decapoda: Pontoniinae), a new mangrove
shrimp from Yap, Caroline Islands.
AB - A new pontoniine shrimp species, Cuapetes yapiensis, from mangroves at Quamun, on
Yap Island, Caroline Islands, is described and illustrated. Cuapetes yapiensis
most closely resembles C. darwiniensis Bruce. Six species of Cuapetes are now
known from the Caroline Islands.
PMID- 25112744
TI - New Mycomya species from the Himalayas (Diptera, Mycetophilidae): 3. Subgenera
Cesamya and Mycomyopsis.
AB - Mycomya Rondani specimens from the Himalayas, mostly Nepal and Myanmar, are
revised. Altogether four species of the subgenus Cesamya Kocak & Kemal and eleven
species of the subgenus Mycomyopsis Vaisanen are recorded from the Himalayas and
the Indian subcontinent. The paper includes a key to the Himalayan species of
Mycomya of the two subgenera. The following fourteen new species are described:
M. aix, M. alticola, M. banteng, M. cissa, M. ducula, M. irena, M. goral, M.
jeti, M. kaa, M. naja, M. niltava, M. pitta, M. sachak, and M. sanar. The
holotype of M. unipectinata Edwards from Sri Lanka was also examined and its
genitalia are described.
PMID- 25112745
TI - Review of genus Nicephora Bolivar (Orthoptera, Tettigoniidae, Meconematinae).
AB - This article presents a revision on all species of genus Nicephora Bolivar, 1900,
describes 1 new species distribute in China ally to this genus. A key to species
of the genus is given.
PMID- 25112746
TI - Systematical studies on the species of the subgenus Bombus (Thoracobombus)
(Hymenoptera: Apidae, Bombus Latreille) in Turkey.
AB - The aim of this study was to analyze the 12 species which belong to the subgenus
Bombus (Thoracobombus) by identifying, collating and testing the applicability of
geometrics morphometrics for distinguishing the species. This was carried out on
133 females and 42 males which were collected from various localities in Turkey.
After digitizing landmarks on the right fore wings, 2-dimensional Cartesian
coordinates were calculated and by Procrustes analysis the coordinates were
standardized and superimposed. Principal Components Analysis (PCA) and Canonical
Variates Analysis (CVA) were performed to show the distribution of all species.
Then, deformations which appeared in thin-plate splines were observed. Mean
values of all the specimens were calculated and Sequential, Agglomerative,
Hierarchical, and Nesting clustering method (SAHN) was performed with these data
to obtain the dissimilarity trees. It can be concluded that all species were
found to have consistently different wing shapes from each other. In females, the
species B. armeniacus, B. mesomelas and B. pomorum which resemble each other,
were also found to be similar based on their wing morphometry. Both in females
and males, the subspecies B. sylvarum citrinofasciatus and B. sylvarum
daghestanicus and the species B. humilis and B. laesus exposed high similarity in
wing morphometry. In males, results showed that the species B. armeniacus and B.
mesomelas and the species B. humilis and B. zonatus have very similar wing shape.
PMID- 25112747
TI - A new name for the oviraptorid dinosaur "Ingenia" yanshini (Barsbold, 1981;
preoccupied by Gerlach, 1957).
AB - The genus name of the small oviraptorid dinosaur Ingenia yanshini is preoccupied
by the tripyloidid nematode Ingenia mirabilis, thus making the former a junior
homonym of the latter. Although "Ingenia" yanshini is sympatric with
Conchoraptor gracilis, it is distinguished from Conchoraptor by proportions of
the manus. It also differs appreciably from the ingeniines Heyuannia huangi and
Nemegtomaia barsboldi in manual and pelvic proportions. "Ingenia" yanshini is
not referable to any other taxon, and is renamed Ajancingenia yanshini gen. nov.
Several specimens originally referred to this species have subsequently been
transferred to new genera, and the taxonomic assignment of material referred to
Ajancingenia yanshini gen. nov. is reassessed.
PMID- 25112748
TI - Tanyproctus (Tanyproctus) arher (Coleoptera: Scarabaeidae: Melolonthinae:
Tanyproctini), a new species from the Socotra Island, Yemen.
AB - Tanyproctus (Tanyproctus) arher Bezdek, Sehnal & Kral, new species, is described
from Socotra Island (Yemen), based on external morphology including male
genitalia.
PMID- 25112749
TI - The first description of adult female of Borboropactus asper (O. P.-Cambridge,
1884) from Sri Lanka (Araneae: Thomisidae).
PMID- 25112750
TI - Description of new species of oak leaf-miners (Lepidoptera: Nepticulidae), with
notes on the species groups of Stigmella Schrank associated with Quercus as a
host-plant.
AB - Stigmella acuta Diskus, Navickaite & Remeikis, sp. nov., a new species of oak
feeding leaf-miner belonging to the S. hemargyrella group, and S. cornuta Rociene
& Stonis, sp. nov., belonging to the newly designated S. cornuta group, are
described from Asia and, for the first time, the S. hemargyrella group is
associated with Quercus as a host-plant. The new species are illustrated with
photographs of the leaf mines, adults, and genitalia. Diagnostics and host-plant
preferences of seven Stigmella species groups associated with oaks (the S.
caesurifasciella, S. saginella, S. quercipulchella, S. ruficapitella, S.
castanopsiella, S. hemargyrella and S. cornuta groups) are discussed.
PMID- 25112751
TI - Studies on the chorionic structure of the eggs of Corixoidea (Hemiptera:
Heteroptera) with scanning electron microscopy.
AB - The chorionic structure of the eggs of sixteen species of Corixoidea
(Ectemnostega (Ectemnostega) quadrata (Signoret), E. (Ectemnostegella) quechua
(Bachmann), Trichocorixa mendozana Jaczewski, Centrocorisa kollari (Fieber),
Heterocorixa brasiliensis Hungerford, Sigara (Aphelosigara) tucma Bachmann, S.
(Tropocorixa) denseconscripta (Breddin), S. (T.) platensis Bachmann, S. (T.)
rubyae (Hungerford), S. (T.) santiagiensis (Hungerford), S. (T.) schadei
(Hungerford), S. (T.) yala Bachmann, Tenagobia (Incertagobia) incerta Lundblad,
T. (Fuscagobia) fuscata (Stal), T. (Schadeogobia) schadei Lundblad, and T.
(Tenagobia) pulchra Hungerford) is described for the first time using scanning
electron microscopy. In addition, the eggs of some of these species are described
based on color and morphometry. The sculpturing of the chorion and the structure
of the micropylar area here in studied using scanning electron microscopy
together with the length of the stalk distinguish the eggs of the genera (except
Sigara, genus without a uniform pattern on the sculpturing of the chorion) and
subgenera (including Aphelosigara and Tropocorixa) of Corixoidea present in
Argentina. The above mentioned characters, together with the egg length, proved
to be useful for the identification of the Argentinian species. An identification
key to the eggs of Argentinian species of Corixoidea based on the material herein
studied, and additional data present in the literature, is provided.
PMID- 25112752
TI - Four new species of genus Parallaxis McAtee (Hemiptera: Cicadellidae:
Typhlocybinae: Dikraneurini) from Argentina, with a key to known species.
AB - Four new species of Parallaxis McAtee are described from Argentina, P. jujuiensis
sp. n., P. misionensis sp. n., P. tucumanensis sp. n. and P. virlai sp. n.
Detailed morphological descriptions and illustrations of the new species and a
key to males of known species are provided.
PMID- 25112753
TI - Four new species of the genus Smaragdina Chevrolat, 1836 from China (Coleoptera:
Chrysomelidae: Cryptocephalinae: Clytrini) .
AB - Four new species are described for the genus Smaragdina, from Sichuan, Yunnan and
Zhejiang provinces of China: Smaragdina tianmuensis sp. nov., S. yajiangensis sp.
nov., S. yangae sp. nov., and S. zhangi sp. nov. The Chinese fauna of the genus
is thus increased to 64 species. Color plates and line drawings of habitus,
maxilla, labium, as well as those characters from the internal morphology like
male genitalia, female spermatheca, and rectal sclerites are provided.
PMID- 25112754
TI - Two new species of Tylototriton from Thailand (Amphibia: Urodela: Salamandridae).
AB - Three morphological groups are found in a salamandrid newt Tylototriton shanjing
from Thailand. We describe two of them as new species, one from northern and the
other from northeastern Thailand, based on molecular and morphological data,
however we could not make a taxonomic decision on the remaining one group because
of the lack of voucher specimens and sufficient genetic data. The northern
species differs morphologically from all known congeners by having the
combination of orange to reddish brown markings, narrow and sharply protruding
dorsolateral bony ridges on head, weakly segmented vertebral ridge, and long and
high tail. The northeastern species is characterized by having the combination of
yellow, orange, or reddish brown markings, wide and moderately protruding
dorsolateral bony ridges on head, smooth vertebral ridge, black limbs, and black
tail except for edges. Validity of taxonomic subdivision of the genus
Tylototriton is discussed.
PMID- 25112755
TI - Description of a new Tiger Snake (Colubridae, Telescopus) from south-western
Africa.
AB - Telescopus finkeldeyi sp. nov. is described from western central to northern
Namibia and south-western Angola. Its maximum size is less than that of the other
three taxa occurring in southern Africa. It is further distinguished by its
fairly variable colour pattern. Although the number of ventrals and the undivided
anal scale are similar to that of T. beetzii, the presence of 19 scale rows
around the middle differs from the 21 rows of T. beetzii.
PMID- 25112756
TI - Three new species of the genus Brachinus Weber, 1801 from the Philippines, with a
modified key to species (Coleoptera: Carabidae: Brachininae).
AB - Three new Brachinus species namely B. grootaerti n. sp. (Palawan Island), B.
palawanensis n. sp. (Palawan Island), B. mindanaoensis n. sp. (Mindanao Island)
from Philippines were described. In addition, a modified key to the known
Brachinus Philippine species is provided.
PMID- 25112757
TI - Loranthophila, a new genus of Australian Lyctinae (Coleoptera: Bostrichidae)
associated with Mistletoe.
AB - Loranthophila gen. n. is described, based on Minthea acanthacollis (Carter &
Zeck), and comparisons are made between this genus and other members of the
bostrichid subfamily Lyctinae.
PMID- 25112758
TI - Annotated list of Tettigoniidae (Orthoptera) from the East Usambara Mountains,
Tanzania and new Tettigoniidae species from East Africa.
AB - A list of the Tettigoniidae (Orthoptera) of the East Usambara Mountains is
presented and 16 new species are described from East Africa. A total number of 29
Tettigoniidae species is recorded for the East Usambara Mountains. New species
are described from the Shimba Hills in Kenya, coastal Tanzania from the
Kazimzumbwi forest reserve, Mt Kilimanjaro, the East and West Usambara and
Uluguru Mountains in Tanzania, namely in Conocephalinae Afroagraecia pwania n.
sp., Afroagraecia shimbaensis n. sp., Afroanthracites discolor n. sp.,
Afroanthracites jagoi n. sp. and Afroanthracites viridis n. sp., in Meconematinae
Afrophisis flagellata n. sp., Afrophisis kisarawe n. sp., Afrophisis
mazumbaiensis n. sp. and Afrophisis pseudoflagellata n. sp., in Hexacentrinae
Aerotegmina megaloptera n. sp., in Mecopodinae Apteroscirtus cristatus n. sp.,
and A. planidorsatus n. sp., in Phaneropterinae Gelotopoia amabilis n. sp., and
in Pseudophyllinae Cymatomerella pardopunctata n. sp. and Cymatomera
viridimaculata n. sp. Seven species are endemic to the East Usambara Mountains
which are 25% of the recorded forest-bound bush crickets. The Tettigoniidae fauna
is compared between the East Usambara Mountains and Mt Kilimanjaro and mechanisms
of speciation discussed in Orthoptera for the area. New Tettigoniidae records are
given for Mt Kilimanjaro (Oxyecous apertus Ragge, Tropidonotacris grandis Ragge
and Eurycorypha conclusa Hemp).
PMID- 25112759
TI - Updated checklist of the ice-crawlers (Insecta: Grylloblattodea: Grylloblattidae)
of North America, with notes on their natural history, biogeography and
conservation.
AB - We provide an updated checklist and comprehensive distributional record of
Grylloblatta (Grylloblattodea: Grylloblattidae) in North America. These
distribution records are based upon a thorough review of the literature, as well
as unpublished data of the authors and colleagues. Thirteen species of
Grylloblatta are currently described, with up to 16 additional taxa awaiting
formal description. Distributional data shows that endemism of Grylloblatta is
high and geographic range size is typically small: the median geographical area
of 13 species and six putative species is 179 km2. It is clear that there is a
general lack of knowledge of species range limits and local population sizes; for
example, three Grylloblatta species are known from just a single locality and
less than 15 specimens each. Conservation status ranks are suggested in order to
update the IUCN Red List and national Natural Heritage Network Database. Finally,
we describe the natural history and seasonality of Grylloblatta, discuss their
unique biogeography, and provide recommendations for future surveys of
grylloblattid species by highlighting known distributional gaps.
PMID- 25112760
TI - Two new species of the genus Temnaspis Lacordaire, 1845, (Coleoptera:
Chrysomeloidea: Megalopodidae) from China and Myanmar, with notes on the biology
of the genus.
AB - Two new species of the genus Temnaspis Lacordaire, 1845, family Megalopodidae,
are described from China and Myanmar: Temnaspis puae Li & H.B. Liang, sp. nov.,
Temnaspis syringa Li & H.B. Liang, sp. nov. Biological notes are provided for
Temnaspis syringa. Temnaspis flavicornis Jacoby, 1892 is redescribed and a
lectotype designated. A key to species of the genus Temnaspis with black elytra
in China and adjacent areas is provided.
PMID- 25112761
TI - Phylogeny of the Cyrtodactylus irregularis species complex (Squamata: Gekkonidae)
from Vietnam with the description of two new species.
AB - The number of described species of bent-toed geckos of the Cyrtodactylus
irregularis species complex in Vietnam has increased from one to eight in the
last six years. We combined morphological and molecular analyses to explore
phylogenetic relationships among all described species in the group. The
phylogeny required the description of two new species, Cyrtodactylus
phuocbinhensis sp. nov. and Cyrtodactylus taynguyenensis sp. nov. Further, the
tree resolved two additional undescribed clades that may also be new species. The
species C. bugiamapensis and C. ziegleri were found to require redefinition.
Cyrtodactylus phuocbinhensis sp. nov. is characterized by a series of enlarged
femoral scales separated from preanal scales while Cyrtodactylus taynguyenensis
sp. nov. does not possess enlarged femoral scales. Both new species are
distinguished from other congeners by a combination of the following characters:
small subcaudal scales, not transversely enlarged; presence (C. phuocbinhensis
sp. nov.) or absence (C. taynguyenensis sp. nov.) of enlarged femoral scales;
number of preanal pores; and dorsal pattern. Genetic distances between described
species and new species were 16.5% and 2.0% in COI and RPL35, respectively, for
C. phuocbinhensis sp. nov., and these distances were 18.8% and 2.2% for C.
taynguyenensis sp. nov., respectively.
PMID- 25112762
TI - A new species of Leptolalax (Anura: Megophryidae) from the highest mountain in
Indochina.
AB - We describe a new species of Leptolalax from northern Vietnam. Leptolalax
botsfordi sp. nov. is distinguished from its congeners by a combination of (1)
supra-axillary and ventrolateral glands present; (2) dark brownish red ventral
surface with white speckling; (3) medium body size for the genus (29.1-32.6 mm in
7 adult males, 30.0-31.8 mm in 2 females); (4) black markings on the flanks
absent; (5) toes with rudimentary webbing and weak lateral fringing; (6) large
pectoral glands (1.1-1.9 mm; 4-6% SVL) and femoral glands (2.4-4.3 mm; 7-14%
SVL); and (7) an advertisement call with a dominant frequency of 2.6-3.2 kHz (at
14.0o C). At present, the new species is known only from upper montane forest
between 2,795-2,815 m elevation on Mount Fansipan, Hoang Lien National Park. To
our knowledge, Leptolalax botsfordi sp. nov. occurs at higher elevations than any
other species in the genus. If L. botsfordi sp. nov. is truly restricted to a
narrow, high-elevation band, it is likely to be particularly vulnerable to the
effects of climate change. The new species also faces the immediate threat of
habitat degradation and pollution due to tourist activity.
PMID- 25112764
TI - Ogleus pilarae, a new genus and species of leptocheliid tanaidacean (Crustacea:
Peracarida: Tanaidomorpha) from the tropical Northwest Atlantic with observations
on the genus Pseudonototanais Lang, 1973.
AB - Ogleus pilarae n. gen., n. sp. (Leptocheliidae) is described from specimens
collected at a depth of 28 m off the eastern coast of Puerto Rico.
Morphologically the new genus appears to have its closest affinities with the
type species of Heterotanais and those of the two subgenera belonging to
Pseudonototanais sensu Gutu. Ogleus is distinguished from these and other
leptocheliids by a combination of characters including a male antennule having
three unfused peduncular articles, five aesthetasc-bearing flagellar articles
with the first being greatly reduced and bearing a single cluster of aesthetascs,
the shape of the male cheliped, and uropods of both sexes having an elongate
endopod with five articles or incipient articles, the distalmost being distinctly
longer than the first. The genus Pseudonototanais is rediagnosed to contain P.
werthi, P. modestus (female holotype), and with reservations P. bransfieldensis.
The Pseudonototanais subgenus Makassaritanais is elevated to full generic rank to
contain M. angustus and M. bamberi. The male originally attributed to P. (M.)
modestus, does not appear to be a leptocheliid since it has a short uropodal
endopod appearing to have just two articles. The taxonomic status of some of the
other taxa previously assigned to Pseudonototanais sensu lato or that are
superficially similar to it is discussed. Overall, based on the females, the
genera Ogleus and Makassaritanais may be more closely allied with genus
Leptochelia Dana, 1849 than to Pseudonototanais and Heterotanais. A key to the
male leptocheliid taxa having truncated or superficially subchelate-appearing
chelae is presented.
PMID- 25112763
TI - Studies in Mexican Tettigoniidae: a new genus of Copiphorini and the first
description of male Conocephalus (Aphauropus) leptopterus Rehn and Hebard and the
female of Insara acutitegmina Fontana, Buzzetti, Marino-Perez & Garcia Garcia.
AB - A new genus belonging to the katydid tribe Copiphorini (Tettigoniidae:
Conocephalinae) is established, Brachycaulopsis gen. nov., collected from the
state of Chiapas, Mexico. Also provided are first descriptions for both the male
of Conocephalus (Aphauropus) leptopterus Rehn & Hebard, 1915 (Conocephalinae:
Conocephalini) and the female of Insara acutitegmina Fontana et al., 2011
(Phaneropterinae: Insarini).
PMID- 25112765
TI - Redescription of Alatina alata (Reynaud, 1830) (Cnidaria: Cubozoa) from Bonaire,
Dutch Caribbean.
AB - Here we establish a neotype for Alatina alata (Reynaud, 1830) from the Dutch
Caribbean island of Bonaire. The species was originally described one hundred and
eighty three years ago as Carybdea alata in La Centurie Zoologique-a monograph
published by Rene Primevere Lesson during the age of worldwide scientific
exploration. While monitoring monthly reproductive swarms of A. alata medusae in
Bonaire, we documented the ecology and sexual reproduction of this cubozoan
species. Examination of forty six A. alata specimens and additional archived
multimedia material in the collections of the National Museum of Natural History,
Washington, DC revealed that A. alata is found at depths ranging from surface
waters to 675 m. Additional studies have reported it at depths of up to 1607 m in
the tropical and subtropical Atlantic Ocean. Herein, we resolve the taxonomic
confusion long associated with A. alata due to a lack of detail in the original
description and conflicting statements in the scientific literature. A new
cubozoan character, the velarial lappet, is described for this taxon. The
complete description provided here serves to stabilize the taxonomy of the second
oldest box jellyfish species, and provide a thorough redescription of the
species.
PMID- 25112766
TI - A new species of Charinus Simon, 1892 from northeastern Brazil with comments on
the potential distribution of the genus in Central and South Americas (Arachnida:
Amblypygi: Charinidae).
AB - A new species of the genus Charinus Simon, 1892 is described from caves in the
Rio Grande do Norte, Brazil. This is the first record of the genus for the state.
This paper presents a map of the Charinus species distribution in Brazil with new
records and a map of potential distribution of the genus in South and Central
Americas. An updated key for Charinus species from Brazil is also presented.
PMID- 25112767
TI - Aglaopheniid hydroids (Cnidaria: Hydrozoa: Aglaopheniidae) from bathyal waters of
the Flemish Cap, Flemish Pass, and Grand Banks of Newfoundland (NW Atlantic) .
AB - Five species of aglaopheniid hydroids (Aglaophenopsis cornuta, Cladocarpus diana,
C. formosus, C. integer, and Nematocarpus ramuliferus) were collected from the
Flemish Cap, Flemish Pass, and Grand Banks of Newfoundland during surveys with
bottom trawls, rock dredges, and scallop gear. All are infrequently reported
species, with C. diana being discovered for the first time since its original
description from Iceland. We document here the southernmost collections of C.
diana and N. ramuliferus, both previously unknown in the western Atlantic. Each
of the five species is described and illustrated based on fertile material, a key
is provided for their identification, and bathymetric distributions are noted.
Known depth ranges are extended for A. cornuta, C. diana, and C. integer.
Aglaophenopsis and Nematocarpus are recognized as genera distinct from the
polyphyletic Cladocarpus, based on the unique structure of the phylactocarp in
the former, and the existence of appendages with nematothecae (ramuli) on almost
all thecate internodes of hydrocladia in the latter. These appendages occur even
in the absence of gonothecae, and are here considered defensive structures that
protect the hydranths. In differing from typical phylactocarps, we accept the
contention that they are characters of generic value.
PMID- 25112768
TI - A new solifugae species of Mummucina Roewer, 1934 (Solifugae, Mummuciidae) from
the Northwest of Argentina.
AB - A new species of Mummuciidae, Mummucina puna sp. nov. (male and female) from
Northwest Puna eco-region of Salta province, Argentina, is described and
illustrated. A key and distribution map of known species of the genus Mummucina
are provided.
PMID- 25112769
TI - Four new troglobiotic species of the genus Megalothorax Willem, 1900 (Collembola:
Neelipleona) from the Carpathian Mountains (Slovakia, Romania).
AB - Four new species of Megalothorax Willem, 1900 are described and illustrated: M.
tatrensis sp. nov., M. carpaticus sp. nov., M. hipmani sp. nov. from caves in
Slovakia and M. draco sp. nov. from the Dracoaia Cave in western Romania. The
species represent troglobiotic forms exhibiting different level of troglomorphy
involving such features as larger body, elongated foot complex, antennae, mucro
and body chaetae. The most pronounced troglomorphy is observed in M. hipmani sp.
nov. and M. draco sp. nov. Species descriptions are completed with comparative
tables of chaetotaxy of antennae and legs. Diagnostic table for all congeners and
dichotomous identification key to the world species are provided. Distribution
records of other Megalothorax species in Slovakia are added.
PMID- 25112770
TI - New species of Floresorchestia from Micronesia living in unusual habitats
(Crustacea, Amphipoda, Talitridae).
AB - The first freshwater talitrid, Floresorchestia pohnpei sp. nov., is described
from the island of Pohnpei, Micronesia. Floresorchestia palau sp. nov. is
described from supralittoral and shallow-water marine habitats in Palau,
Micronesia.
PMID- 25112771
TI - Neoliomera moana, a new cavernicolous species of xanthid crab from the Marquesas
Islands (Crustacea: Decapoda: Brachyura).
AB - A new crab Liomerinae, Neoliomera moana sp. nov., is described from the Marquesas
Islands, based on three specimens collected by hand at the entrance of submarine
caves at depths of 6-28 m. Within the genus the new species belongs to a group of
six species that have the carapace cristate on the anterolateral margins. It can
be recognized by the presence of a double crest on the upper margin of the palm
of chela and by its colour pattern, with about twenty red spots on the dorsal
surface of the carapace. This new species is considered has a potential endemic
form to the Marquesas Islands.
PMID- 25112772
TI - Neostylidium, a new generic replacement name for Stylidium Dall 1907 (Gastropoda:
Caenogastropoda: Cerithiidae) non Eichwald 1855 (Anthozoa).
PMID- 25112773
TI - The genus Asuridia Hampson, 1900 in Taiwan, with descriptions of two new species
(Erebidae, Arctiinae, Lithosiini).
PMID- 25112775
TI - Circulating hematopoietic progenitor cells in essential thrombocythemia versus
prefibrotic/early primary myelofibrosis.
PMID- 25112776
TI - Enhanced separation of potassium ions by spontaneous K+-induced self-assembly of
a novel metal-organic framework and excess specific cation-pi interactions.
AB - A novel metal-organic framework (MOF) was fabricated by spontaneous K(+)-induced
supramolecular self-assembly with the embedded tripodal ligand units. When the 3D
ligand was loaded onto Fe3O4@mSiO2 core-shell nanoparticles, it could effectively
separate K(+) ions from a mixture of Na(+), K(+), Mg(2+), and Ca(2+) ions through
nanoparticle-assisted MOF crystallization into a Fe3O4@mSiO2@MOF hybrid material.
Excess potassium ions could be extracted because of the specific cation-pi
interaction between K(+) and the aromatic cavity of the MOF, leading to enhanced
separation efficiency and suggesting a new application for MOFs.
PMID- 25112778
TI - MRI dedicated to bones and joints: what are their market shares in terms of
number of patients in private practice in France?
AB - PURPOSE: The French government plans to install MRI facilities dedicated to
musculoskeletal indications. We have analyzed the use of imaging investigations
in the community to assess their market share. MATERIALS AND METHODS: We
undertook a retrospective analysis of all reimbursements during the year 2012 by
the French Social Plan for Independent Workers for 4 imaging methods for a
musculoskeletal indication (MRI, CT scan with or without opacification and
contrast-enhanced conventional radiography). RESULTS: Three hundred and thirty
two thousand eight hundred and ninety-three beneficiaries were included. The
following investigations were used: MRI 12659 investigations; CT scan without
direct opacification 7392; CT scan with direct opacification 1271; contrast
enhanced conventional radiography 1187. Of those beneficiaries who underwent
investigations of the spine, 39.91% had MRI alone, 8.62% had both MRI and one of
the other investigations and 51.46% did not have MRI. The corresponding figures
for beneficiaries undergoing lower limb investigations were 79.57%, 4.53% and
15.90% and those for beneficiaries undergoing upper limb investigations were
35.49%, 6.56% and 57.94% respectively. CONCLUSION: In terms of the numbers of
investigations, our results show that in France MRI dedicated to musculoskeletal
indications has a wide market share for the spine, upper and lower limbs.
PMID- 25112777
TI - Increased Platelet Distribution Width Is Associated With Severity of Coronary
Artery Disease in Patients With Acute Coronary Syndrome.
AB - Platelet activation plays a pivotal role in acute coronary syndrome (ACS). We
investigated the relationship between platelet distribution width (PDW) and
severity of coronary artery disease (CAD) in patients with ACS. A total of 502
patients with ACS were enrolled. High (n = 151) and low PDW (n = 351) groups were
defined as patients having values in the third tertile (>17%) and lower 2
tertiles (<=17%). There were significantly higher Gensini score (44 [10-168] vs.
36 [2-132], P < .001), and neutrophil-lymphocyte ratio (3.1 [0.8-12.4] vs. .2.5
[0.3-13], P = .012) and baseline platelet counts were significantly lower (220
[61-623] vs. 233 [79-644] 10(3)/mm3, P = .022) in the high PDW group. The
variables PDW >17%, diabetes mellitus, and myocardial infarction were found to be
associated with high Gensini score (odds ratio [OR]: 1.91, 95% confidence
interval [CI]: 1.27-2.88, P = .002; OR: 2.85, 95% CI: 1.91-4.25, P < .001; OR:
2.67, 95% CI:1.74-4.1, P < .001, respectively). An increased PDW (>17%) is
associated with severity of CAD in patients with ACS.
PMID- 25112780
TI - High-density monolayers of metal complexes: preparation and catalysis.
AB - Catalysts are one of the key materials for realizing a sustainable society.
However, we may encounter problematic cases where conventional catalyst systems
cannot provide effective solutions. We thus believe that the establishment of
novel methods of catalyst preparation is currently necessary. Utilization of high
density monolayers of molecular metal complexes is our strategy, and we expect
that this methodology will enable facile and systematic screening of unique and
efficient catalysts. This Personal Account describes our challenges to establish
such an immature method in catalyst preparation as well as the related background
and perspective. Preparation and catalysis by high-density monolayers of Rh
complexes with N-heterocyclic carbene, structurally compact phosphine and
diisocyanide ligands on gold surfaces are presented. The catalytic application of
a high-density Pd-bisoxazoline complex prepared on a single-crystal silicon
surface is also shown. Uniquely high catalyst turnover numbers and high
chemoselectivities were observed with these catalyst systems.
PMID- 25112779
TI - Influences of age, gender, and circadian rhythm on deceleration capacity in
subjects without evident heart diseases.
AB - BACKGROUND: Deceleration capacity (DC) is a newly found predictor of mortality
after myocardial infarction. Age-, gender-, and circadian rhythm-related
differences in DC may limit its predictive value, which should be considered in
clinical settings. METHODS: DC, average heart rate, and HRV parameters, including
24 hours, awaking state (15:00-20:00) and sleeping mode (00:00-05:00) strips from
24 hours Holter recordings in 636 subjects without heart diseases were examined.
Heart rate variability was analyzed in time domains (standard deviation of all
normal-to-normal intervals [SDNN], normal-to-normal RR intervals in all 5-minute
segments [SDANN], and root mean square successive difference [RMSSD]). RESULTS:
The DC, SDNN, SDANN, RMSSD, and heart rate decreased with age. Deceleration
capacity was significantly lower in patients greater than 50 years of age. The
largest decrease of SDNN, SDANN, and RMSSD occurred in patients 30-39 years of
age. The values of SDNN, SDANN, and DC of women were lower than that of men in
the young and middle-aged groups, but age-related decrease of DC in men was
greater than that in women. Heart rate of women was significantly higher than
that of men in younger subjects, especially in a sleeping mode. There were higher
values of DC and RMSSD during sleeping than that during a waking state.
CONCLUSIONS: The age, gender, and circadian rhythm may be useful when evaluating
cardiac autonomic function and need to be considered when evaluating DC and HRV
in clinical and scientific researches.
PMID- 25112782
TI - The acceptability and usefulness of mindfulness-based cognitive therapy for
people living with psoriasis: a qualitative study.
PMID- 25112781
TI - Impact of the expression of thymidylate synthase and dihydropyrimidine
dehydrogenase genes on survival in stage II/III gastric cancer.
AB - BACKGROUND: The efficacy of 5-fluorouracil (5FU)-based therapy, which remains the
cornerstone of gastrointestinal cancer treatment, depends upon the expression of
enzymes involved in pyrimidine metabolism, including thymidylate synthase (TS),
dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate
phosphoribosyltransferase (OPRT). We analyzed the expression of these genes in
patients enrolled in the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer
(ACTS-GC) and their possible roles as biomarkers for treatment outcomes. METHODS:
Formalin-fixed, paraffin-embedded specimens were available for 829 of a total of
1,059 (78.3 %) patients. TS, DPD, TP, and OPRT expression was measured by RT-PCR
in manually microdissected tumor specimens and normalized to the reference gene,
beta-actin. The expression level of each gene was categorized as low or high
using cutoffs at the 33.3rd, 50th, or 66.7th percentiles. RESULTS: The hazard
ratio (HR) for overall survival (OS) after S-1 treatment versus surgery alone was
significantly lower in high (>66.7th percentile; HR = 0.370; 95 % CI 0.221-0.619)
compared to low (<66.7th percentile; HR = 0.757; 95 % CI 0.563-1.018) TS
expression groups (P = 0.015). Similarly, the HR for OS after S-1 therapy versus
surgery alone was significantly lower in high (>33.3rd percentile; HR = 0.520, 95
% CI 0.376-0.720) compared to low (<33.3rd percentile; HR = 0.848, 95 % CI 0.563
1.276) DPD expression groups (P = 0.065). There was no interaction between TP or
OPRT expression and OS. CONCLUSIONS: This large biomarker study showed that high
TS and DPD gene expression in tumors was associated with enhanced benefit from
postoperative adjuvant S-1 treatment in gastric cancer. There was no interaction
between TP and OPRT expression and S-1 treatment.
PMID- 25112784
TI - Neurocomputational account of memory and perception: Thresholded and graded
signals in the hippocampus.
AB - Recent evidence suggests that the hippocampus, a region critical for long-term
memory, also supports certain forms of high-level visual perception. A seemingly
paradoxical finding is that, unlike the thresholded hippocampal signals
associated with memory, the hippocampus produces graded, strength-based signals
in perception. This article tests a neurocomputational model of the hippocampus,
based on the complementary learning systems framework, to determine if the same
model can account for both memory and perception, and whether it produces the
appropriate thresholded and strength-based signals in these two types of tasks.
The simulations showed that the hippocampus, and most prominently the CA1
subfield, produced graded signals when required to discriminate between highly
similar stimuli in a perception task, but generated thresholded patterns of
activity in recognition memory. A threshold was observed in recognition memory
because pattern completion occurred for only some trials and completely failed to
occur for others; conversely, in perception, pattern completion always occurred
because of the high degree of item similarity. These results offer a
neurocomputational account of the distinct hippocampal signals associated with
perception and memory, and are broadly consistent with proposals that CA1
functions as a comparator of expected versus perceived events. We conclude that
the hippocampal computations required for high-level perceptual discrimination
are congruous with current neurocomputational models that account for recognition
memory, and fit neatly into a broader description of the role of the hippocampus
for the processing of complex relational information.
PMID- 25112783
TI - A randomised clinical trial to evaluate the effects of Plantago ovata husk in
Parkinson patients: changes in levodopa pharmacokinetics and biochemical
parameters.
AB - BACKGROUND: Plantago ovata husk therapy could be used in patients with Parkinson
disease to reduce the symptoms of gastrointestinal disorders, but it is important
to know whether this compound modifies levodopa pharmacokinetics. The maintenance
of constant plasma concentrations of levodopa abolishes the clinical fluctuations
in parkinsonian patients. The aim of this randomised clinical trial was to
establish the influence of the fiber Plantago ovata husk in the pharmacokinetics
of levodopa when administered to Parkinson patients well controlled by their oral
medication. METHODS: To evaluate the effects of this fiber on several biochemical
parameters. 18 volunteers participated in the study and received alternatively
two treatments (Plantago ovata husk or placebo) with their usual
levodopa/carbidopa oral dose. On days 0 (initial situation), 14 and 35 of the
study, blood samples were taken to assess levodopa pharmacokinetics and to
determine biochemical parameters. RESULTS: Levodopa Cmax was very similar in the
initial situation (603.2 ng/ml) and after placebo administration (612.0 ng/ml),
being slightly lower (547.8 ng/ml) when Plantago ovata husk was given. AUC was
very similar in the three groups: initial situation.- 62.87 MUg.min/ml, fiber
treatment.- 64.47 MUg.min/ml and placebo treatment.- 65.10 MUg.min/ml. Fiber
reduced significantly the number of peaks observed in the levodopa
concentrations, maintaining concentrations more stable. No significant
differences were found in total cholesterol, LDL-cholesterol and triglycerides
with the administration of Plantago ovata husk. CONCLUSIONS: Plantago ovata husk
administration caused a smoothing and homogenization of levodopa absorption,
providing more stable concentrations and final higher levels, resulting in a
great benefit for patients. TRIAL REGISTRATION: EudraCT2006-000491-33.
PMID- 25112786
TI - Mating system and environmental variation drive patterns of adaptation in
Boechera spatifolia (Brassicaceae).
AB - Determining the relative contribution of population genetic processes to the
distribution of natural variation is a major goal of evolutionary biology. Here,
we take advantage of variation in mating system to test the hypothesis that local
adaptation is constrained by asexual reproduction. We explored patterns of
variation in ecological traits and genome-wide molecular markers in Boechera
spatifolia (Brassicaceae), a species that contains both apomictic (asexual) and
sexual individuals. Using a combination of quantitative genetics, neutral genetic
(SSR) and genome-wide single nucleotide polymorphism, we assessed the hypothesis
that asexual lineages should have reduced signatures of adaptation relative to
sexual conspecifics. All three measures (traits, SSRs, SNPs) demonstrated that
apomicts are genetically distinct from sexuals, regardless of population
location. Additionally, phylogenetic clustering revealed that the apomictic group
shared a single common ancestor. Across the landscape, sexual genome-wide SNP
variation was strongly associated with latitude (r(2) > 0.9), indicating that
sexual populations have differentiated across an environmental gradient.
Furthermore, flowering time and growth rate, as assessed in a common garden,
strongly covary with the elevation and latitude of the source population. Despite
a wide geographic distribution that largely overlaps with sexual populations,
there was little evidence for differentiation in molecular markers or
quantitative characters among apomictic populations. Combined, these data
indicated that, in contrast to asexual populations, sexual populations show
evidence of local adaptation.
PMID- 25112785
TI - Toxicity and quality of life after choline-PET/CT directed salvage lymph node
dissection and adjuvant radiotherapy in nodal recurrent prostate cancer.
AB - BACKGROUND: In a previous study we demonstrated that, based on 11C/18 F-choline
positron emission tomography-computerized-tomography as a diagnostic tool,
salvage lymph node dissection (LND) plus adjuvant radiotherapy (ART) is feasible
for treatment of pelvic/retroperitoneal nodal recurrence of prostate cancer
(PCa). However, the toxicity of this combined treatment strategy has not been
systematically investigated before. The aim of the current study was to evaluate
the acute and late toxicity and quality of life of ART after LND in
pelvic/retroperitoneal nodal recurrent PCa. MATERIAL AND METHODS: 43 patients
with nodal recurrent PCa were treated with 46 LND followed by ART (mean 49.6 Gy
total dose) at the sites of nodal recurrence. Toxicity of ART was analysed by
physically examination (31/43, 72.1%), by requesting 15 frequent items of adverse
events from the Common-Terminology-Criteria for Adverse Events Version 4.0
catalogue and by review of medical records. QLQ-C30 (EORTC quality of life
assessment) and PR25 (prostate cancer module) questionnaires were used to
investigate quality of life. Toxicity was evaluated before starting of ART,
during ART (acute toxicity), after ART (mean 2.3 months) and at end of follow up
(mean 3.2 years after end of ART) reflecting late toxicity. RESULTS: 71.7%
(33/46) of 46 ART were treatment of pelvic, 10.9% (5/46) of retroperitoneal only
and 28.3% (13/46) of pelvic and retroperitoneal regions. Overall 52 symptoms
representing toxicities were observed before ART, 107 during ART, 88 after end of
ART and 52 at latest follow up. Leading toxicities during ART were diarrhoea
(19%, 20/107), urinary incontinence (16%, 17/107) and fatigue (16%, 17/107). The
spectrum of late toxicities was almost equal to those before beginning of ART. No
grade 3 adverse events or chronic lymphedema at extremities were observed. We
observed no clear correlation between localisation of treated regions, technique
of ART and frequency or severity of toxicities. Mean quality of life at final
evaluation was 74%. CONCLUSION: ART after extended LND in PCa relapse is
justifiable with respect to adverse effects and toxicity. The side effects were
circumscribed and well tolerated. The spectrum of adverse events at latest follow
up was almost equal to those before start of ART.
PMID- 25112787
TI - Pathophysiology of blast-induced ocular trauma in rats after repeated exposure to
low-level blast overpressure.
AB - BACKGROUND: The incidence of blast-induced ocular injury has dramatically
increased due to advances in weaponry and military tactics. A single exposure to
blast overpressure (BOP) has been shown to cause damage to the eye in animal
models; however, on the battlefield, military personnel are exposed to BOP
multiple times. The effects of repeated exposures to BOP on ocular tissues have
not been investigated. The purpose of this study is to characterize the effects
of single or repeated exposure on ocular tissues. METHODS: A compressed air shock
tube was used to deliver 70 +/- 7 KPa BOP to rats, once (single blast
overpressure [SBOP]) or once daily for 5 days (repeated blast overpressure
[RBOP]). Immunohistochemistry was performed to characterize the pathophysiology
of ocular injuries induced by SBOP and RBOP. Apoptosis was determined by
quantification activated caspase 3. Gliosis was examined by detection of glial
fibrillary acidic protein (GFAP). Inflammation was examined by detection of CD68.
RESULTS: Activated caspase 3 was detected in ocular tissues from all animals
subjected to BOP, while those exposed to RBOP had more activated caspase 3 in the
optic nerve than those exposed to SBOP. GFAP was detected in the retinas from all
animals subjected to BOP. CD68 was detected in optic nerves from all animals
exposed to BOP. CONCLUSION: SBOP and RBOP induced retinal damage. RBOP caused
more apoptosis in the optic nerve than SBOP, suggesting that RBOP causes more
severe optic neuropathy than SBOP. SBOP and RBOP caused gliosis in the retina and
increased inflammation in the optic nerve.
PMID- 25112788
TI - Altered expression of transforming growth factor-beta isoforms in bovine cystic
ovarian disease.
AB - Cystic ovarian disease (COD) is one of the main causes of infertility in dairy
cattle. It has been shown that intra-ovarian factors may contribute to follicular
persistence. Transforming growth factor-beta (TGFB) isoforms are important
paracrine and autocrine signalling molecules that regulate ovarian follicle
growth and physiology. Considering the importance of these factors in the ovarian
physiology, in this study, we examined the expression of TGFB isoforms (TGFB1,
TGFB2 and TGFB3) in the ovary of healthy cows and animals with spontaneous and
adrenocorticotrophic hormone (ACTH)-induced COD. In the oestrous-synchronized
control group, the expression of TGFB1 in granulosa and theca cells was higher in
spontaneous cysts than in atretic or tertiary follicles. When we compared TGFB2
expression in granulosa cells from atretic or tertiary follicles from the
oestrous-synchronized control group with that in ACTH-induced or spontaneous
follicular cysts, we found a higher expression in the latter. The expression of
the TGFB isoforms studied was also altered during folliculogenesis in both the
spontaneous and ACTH-induced COD groups. As it has been previously shown that
TGFB influences steroidogenesis, ovarian follicular proliferation and apoptosis,
an alteration in its expression may contribute to the pathogenesis of this
disease.
PMID- 25112790
TI - Left ventricular ejection fraction by real-time three-dimensional
echocardiography : The Necker cube for the naive realism of two-dimensional
methods.
PMID- 25112789
TI - Effect of genetic and climatic variability on the metabolic profiles of black
gram (Vigna mungo L.) seeds and sprouts.
AB - BACKGROUND: Black gram is becoming increasingly of interest for consumers
worldwide. The metabolomics have been conducted to reflect the life history of
each individual plant. The metabolic pattern of black gram seeds and sprouts was
profiled to investigate genetic and climatic influences on a broad range of
chemical constituents. RESULTS: Distinct differences in metabolite profiles among
three black gram varieties for both intact seeds and sprouts were observed. The
differential impact of climate on metabolite profiles of the variety Chai Nat 80
during both dry and rainy seasons was investigated. Univariate statistical
analysis demonstrated that greater maturity due to adequate moisture in the rainy
season led to a higher content of nutritionally relevant polar metabolites,
whereas the dry season resulted in a high relative amount of storage lipid
because of immaturity due to insufficient rain and water supply. CONCLUSION: The
investigation confirmed the potential of metabolite profiling to assist in
breeding and farming practices.
PMID- 25112791
TI - The relationship between self-injurious behavior and self-disclosure in
adolescents with eating disorders.
AB - PURPOSE: The aim of the current study is to examine the association between self
disclosure and self-injurious behaviors among adolescent patients diagnosed with
an eating disorder. METHODS: Sixty three female patients who fulfilled the DSM-IV
diagnostic criteria of eating disorders were included (i.e. anorexia, bulimia,
binge eating disorder and eating disorders not otherwise specified).
Participants' age ranged from 11.5 to 20 years (M = 15.42, SD = 1.82).
Participants completed self- report questionnaires about eating disorders, self
disclosure, self-injurious behaviors (FASM) and depression (BDI-II) RESULTS:
82.5% of the sample endorsed severe self-injurious behaviors. A moderate negative
relationship was found between general disclosure to parents and self-injurious
behaviors indicating that patients who generally self-disclose to their parents
(on different topics, apart from suicidal ideation) engage less frequently in
self-injurious behaviors. In addition, the more patients self-disclose their
suicidal ideation to others, the more they tend to self-injure. CONCLUSION: Self
disclosure to parents on any topic may buffer against self-injurious behaviors
and therefore it is important to work with adolescents suffering from eating
disorders on effective self disclosure. In addition, self-disclosure about
suicidal ideation to others by adolescents suffering from eating disorders should
always be taken seriously, since it may be related to self-injurious behaviors.
PMID- 25112792
TI - Suicidal behaviour and memory: A systematic review and meta-analysis.
AB - OBJECTIVES: Suicidal behaviour results from a complex interplay between stressful
events and vulnerability factors, including cognitive deficits. It is not yet
clear if memory impairment is part of this specific vulnerability. Therefore, the
objective of this study was to examine the association between memory deficits
and vulnerability to suicidal acts. METHODS: A literature review was performed
using Medline, Embase, and PsycInfo databases. Twenty-four studies (including
2,595 participants) met the selection criteria. Four different types of memory
(i.e., working memory, short- and long-term memory, and autobiographical memory)
were assessed in at least three different studies. RESULTS: Autobiographical
memory was significantly less specific and more general in patients with a
history of suicide attempt relative to those without such a history (Hedges' g =
0.8 and 0.9, respectively). Long-term memory and working memory were both more
impaired in suicide attempters than in patient and healthy controls. Only short
term memory did not differentiate suicide attempters from patient controls.
CONCLUSIONS: Memory may play a significant role in the risk of suicidal acts,
perhaps by preventing these individuals from using past experiences to solve
current problems and to envision the future, and by altering inhibitory
processes. More studies are necessary to better clarify these relationships.
PMID- 25112793
TI - Controversy in mitral valve repair, resection or chordal replacement?
AB - Mitral valve plasty has superseded valve replacement as the standard technique
for treating degenerative mitral valve prolapse. Quadrangular resection is
considered the gold standard for posterior leaflet prolapse. Chordal replacement
was first developed to treat the anterior leaflet and subsequently became widely
used for the posterior leaflet, after which a new version of posterior leaflet
resection was developed that did not involve local annular plication. In the era
of the mini-thoracotomy, the premeasured loop technique is simple to adopt and is
as durable as quadrangular resection. However, there is controversy surrounding
whether resection or chordal replacement is the optimal technique. The resection
technique is curative because it removes the main pathologic lesion. The
disadvantage of the resection is that it can be complicated and often requires
advanced surgical skills. In contrast, chordal replacement is not pathologically
curative because it leaves behind a redundant leaflet. However, the long-term
results appear to be equivalent in many reports. Functionally, chordal
replacement retains greater posterior leaflet motion with a lower trans-mitral
pressure gradient than quadrangular resection. Moreover, chordal replacement is
simple and yields uniform results. The optimal technique depends on whether the
anterior leaflet or posterior leaflet is involved, the Barlow or non-Barlow
disease state, and whether a mini-thoracotomy or standard sternotomy approach is
used. For mitral valve repair, the most superior and reliable technique for the
posterior leaflet is resection using the newer resection technique with a
sternotomy approach, which requires a skilled surgeon.
PMID- 25112794
TI - Richards-like two species population dynamics model.
AB - The two-species population dynamics model is the simplest paradigm of inter- and
intra-species interaction. Here, we present a generalized Lotka-Volterra model
with intraspecific competition, which retrieves as particular cases, some well
known models. The generalization parameter is related to the species habitat
dimensionality and their interaction range. Contrary to standard models, the
species coupling parameters are general, not restricted to non-negative values.
Therefore, they may represent different ecological regimes, which are derived
from the asymptotic solution stability analysis and are represented in a phase
diagram. In this diagram, we have identified a forbidden region in the mutualism
regime, and a survival/extinction transition with dependence on initial
conditions for the competition regime. Also, we shed light on two types of
predation and competition: weak, if there are species coexistence, or strong, if
at least one species is extinguished.
PMID- 25112796
TI - Motion analysis of the upper extremity in children with unilateral cerebral palsy
-an assessment of six daily tasks.
AB - Restrictions in range of motion of the upper extremity are common in patients
with unilateral cerebral palsy (CP). The purpose of this study was to investigate
movement deviations of the upper extremity in children with unilateral CP by
means of 3D motion capture as well as by the use of easy to use scores and
questionnaires (MACS, MRC, MAS, ABILHAND-Kids). 16 children with a spastic,
unilateral CP were included and compared to a group of 17 typically developing
adolescents (TD). The movement time and range of motion (ROM) of six uni- and
bimanual daily tasks were compared and correlated with the scores and
questionnaires. Movement times increased significantly with involvement according
to MACS in all tasks. The restrictions in ROM were pronounced in the forearm. As
a compensatory mechanism the children of the MACS 2 and 3 groups showed increased
trunk movement. Furthermore, there was a positive correlation between the MACS
and the ABILHAND-Kids Questionnaire. In contrast to previous studies, which
reported a correlation between the restrictions in ROM and the MACS, this study
showed no consistent correlation between the restrictions in ROM neither with the
MACS nor with the ABILHAND-Kids. While the MACS and the ABILHAND-Kids function as
a simple rating tool for clinical use, the detailed analysis of different daily
tasks using 3-D-motion capture provides more detailed information about the
movement deviations and spatiotemporal parameters.
PMID- 25112795
TI - Patterns of change in nonverbal cognition in adolescents with Down syndrome.
AB - This study was designed to examine longitudinal change in nonverbal cognitive
abilities across adolescence for 20 males with Down syndrome (DS). We used
hierarchical linear modeling to examine the rate of change in performance on the
subtests of the Leiter-R Brief IQ across four annual time points and to determine
the relation between maternal IQ and level and rate of change in performance.
Results indicated no significant change in IQ (standard scores) with age in the
sample, suggesting IQ stability during adolescence for individuals with DS,
although several participants performed at floor level on the standard scores for
the Leiter-R, limiting interpretation. Growth scores, however, provide a metric
of absolute ability level, allow for the examination of change in Leiter-R
performance in all participants, and minimize floor effects. Results from the
analysis of growth scores indicated significant gain in absolute nonverbal
cognitive ability levels (growth score values) over time for the adolescents with
DS, although the growth varied by subdomain. Maternal IQ did not explain
variability in cognitive performance or change in that performance over time in
our sample of adolescents with DS.
PMID- 25112797
TI - Effect of concentration on the formation of rose bengal triplet state on
microcrystalline cellulose: a combined laser-induced optoacoustic spectroscopy,
diffuse reflectance flash photolysis, and luminescence study.
AB - Laser-induced optoacoustic spectroscopy (LIOAS), diffuse reflectance laser flash
photolysis (DRLFP), and laser-induced luminescence (LIL) have been applied in
conjunction to the determination of triplet state quantum yields of Rose Bengal
(RB) supported on microcrystalline cellulose, a strongly light-scattering solid.
Among the three used methods, the only one capable of providing absolute triplet
quantum yields is LIOAS, but DRLFP and LIL aid in demonstrating that the LIOAS
signal arises in fact from the triplet state and confirm the trend found with RB
concentration. The coherence found for the three techniques demonstrates the
usefulness of the approach. Observed triplet quantum yields are nearly constant
within a limited concentration range, after which they decay strongly due to the
generation of inactive dye aggregates or energy trapping centers. When quantum
yields are divided by the fraction of absorbed light exciting the dye, the
quotient falls off steadily with concentration, following the same trend as the
observed fluorescence quantum yield. The conditions that maximize triplet
formation are determined as a compromise between the rising light absorption and
the decrease of quantum yield with RB concentration.
PMID- 25112798
TI - NMR crystallography: Applications to inorganic materials.
AB - Current developments of NMR crystallography as well as some recent applications
to diamagnetic inorganic solids are presented. First, we illustrate how solid
state NMR data can be used in combination with diffraction data for the
determination of the periodic part of the crystal structures, from the space
group selection, to the structure determination over the refinement and
validation processes. As ss-NMR, contrary to diffraction (powder and single
crystal), is not restricted to periodic boundary conditions, ss-NMR data can be
used to further complete the structural description of materials, including
studies of local order/disorder, etc. This illustrated through examples, which
are shown and discussed in the second part of this review.
PMID- 25112799
TI - Obesity is a determinant of arterial stiffness independent of traditional risk
factors in Asians with young-onset type 2 diabetes.
AB - OBJECTIVE: Type 2 diabetes (T2DM) among the young population has become a serious
concern globally, presumably due to the rising trend of obesity. Compared to
other forms of diabetes, young-onset T2DM experiences more cardiovascular events
and other vascular complications although the underlying mechanisms remain
largely unknown. Increased arterial stiffness is a hallmark of vasculopathy. We
aim to study the clinical and metabolic determinants of arterial stiffness in a
cohort of multi-ethnic Asians with young-onset T2DM. METHODS: 179 subjects with
T2DM onset age below 30 years old were selected in this cross sectional study.
Arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWV).
RESULTS: PWV was correlated with age, duration of diabetes, systolic blood
pressure, alanine aminotransferase, urinary albumin-to-creatinine ratio (ACR) and
eGFR in bivariate correlation analysis. However, PWV was only significantly
correlated with body mass index (BMI), waist circumference, urinary ACR and eGFR
after adjustment for age. Overweight individuals with young-onset T2DM had
significantly higher PWV levels compared to their lean counterparts (7.3 +/- 2.4
m/s vs 6.4 +/- 2.3 m/s, p = 0.072 and p < 0.0001 without and with adjustment for
age, respectively). Multivariable regression models revealed that age, BMI, eGFR
and usage of insulin were independently associated with PWV. These 4 variables
explained 35.5% variance in PWV levels. CONCLUSION: Age, BMI, renal function and
insulin usage are the main determinants of PWV levels in Asians with young-onset
T2DM. Notably, obesity is a modifiable determinant of arterial stiffness
independent of high blood pressure, dyslipidemia and hyperglycemia in this
population.
PMID- 25112800
TI - Hemoglobin, iron metabolism and angiographic coronary artery disease (The
Ludwigshafen Risk and Cardiovascular Health Study).
AB - BACKGROUND: Anemia has been shown to be a risk factor for coronary artery disease
and mortality. The involvement of body iron stores in the development of CAD
remains controversial. So far, studies that examined hemoglobin and parameters of
iron metabolism simultaneously do not exist. METHODS AND RESULTS: Hemoglobin and
iron status were determined in 1480 patients with stable angiographic coronary
artery disease (CAD) and in 682 individuals in whom CAD had been ruled out by
angiography. The multivariate adjusted odds ratios (OR) for CAD in the lowest
quartiles of hemoglobin and iron were 1.62 (95%CI: 1.22-2.16), and 2.05 (95%CI:
1.51-2.78), respectively compared to their highest gender-specific quartiles. The
fully adjusted ORs for CAD in the lowest quartiles of transferrin saturation,
ferritin (F) and soluble transferrin receptor (sTfR)/log10F index were 1.69
(95%CI: 1.25-2.27), 1.98 (95%CI: 1.48-2.65), and 1.64 (95%CI: 1.23-2.18),
respectively compared to their highest gender-specific quartiles. When adjusting
in addition for iron and ferritin the OR for CAD in the lowest quartiles of
hemoglobin was still 1.40 (95%CI: 1.04-1.90) compared to the highest gender
specific quartiles. Thus, the associations between either iron status or low
hemoglobin and CAD appeared independent from each other. The sTfR was only
marginally associated with angiographic CAD. CONCLUSIONS: Both low hemoglobin and
iron depletion are independently associated with angiographic CAD.
PMID- 25112801
TI - Single nucleotide polymorphism of CYP3A5*3 contributes to clopidogrel resistance
in coronary artery disease patients among Tamilian population.
AB - Clopidogrel is an antiplatelet drug. It is used for the treatment as well as for
the prophylaxis of coronary artery disease. Clopidogrel resistance is an emerging
problem in clinical settings. The aim of the present study was to evaluate the
effect of CYP3A5*3 genetic polymorphism on clopidogrel resistance. One hundred
and forty-seven patients from outpatient Department of Cardiology on 75 mg/day of
clopidogrel as maintenance dose were recruited from April 2010 to July 2011. All
subjects gave written informed consent to participate in the study. DNA
extraction was performed using phenol chloroform extraction procedure and
genotyping by standard Taqman based RT-PCR method. Platelet aggregation was done
at the end of 7th and 14th day by using chronolog lumi Aggregometer which is
expressed as impedance in ohms. Impedance values of >5 ohms at the end of 6 min
were considered as clopidogrel resistance. Subjects (N = 147) were analysed for
CYP3A5*3 polymorphism, of which 49 (33%) were found to be clopidogrel resistant.
Homomutants of CYP3A5*3 gene had 2.78 (0.97-7.98; p < 0.05) fold risk and
heteromutants had 2.4 (0.93-6.46; p < 0.05) fold risk of developing clopidogrel
resistance. Carriers of defective allele G of CYP3A5*3 had higher propensity to
cause clopidogrel resistance with an odds ratio of 1.63. Variant alleles and
genotypes of CYP3A5*3 polymorphism contributed significantly to clopidogrel
resistance with a higher odds ratio. Thus, pharmacogenomics paves way for the
emergence of stratified medicine in clopidogrel therapy and personalised
pharmacotherapy in ischaemic heart disease.
PMID- 25112802
TI - The true incidence of traumatic spinal cord injuries.
PMID- 25112804
TI - [The new tools of microbiological diagnosis of tuberculosis].
AB - This review focuses on the role of new tools in the "modern" microbiological
diagnosis of tuberculosis. Traditional techniques of microscopy and culture
remain essential to diagnostic certainty, but some innovations replace daily the
older techniques such as the identification of Mycobacterium tuberculosis complex
by immunochromatography or mass spectrometry MALDI-TOF type from positive
cultures, or susceptibility testing in liquid medium. New tools that use
molecular techniques have become important. They all have in common to optimize
the fight against tuberculosis by reducing diagnostic delay. They also allow
rapid detection of drug resistance. However, the techniques of gene amplification
directly from clinical samples are still less sensitive than culture.
Bacteriological diagnosis of tuberculosis disease therefore still relies on the
complementarities of different phenotypic and molecular techniques.
PMID- 25112805
TI - [A rare cause of chondritis].
PMID- 25112803
TI - Sinus node dysfunction in catecholaminergic polymorphic ventricular tachycardia:
risk factor and potential therapeutic target?
AB - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited
heart rhythm disorder characterized by the occurrence of potentially life
threatening polymorphic ventricular tachyarrhythmias in conditions of physical or
emotional stress. The underlying cause is a dysregulation in intracellular Ca
handling due to mutations in the sarcoplasmic reticulum Ca release unit. Recent
experimental work suggests that sinus bradycardia, which is sometimes observed in
CPVT patients, may be another primary defect caused by CPVT mutations. Herein, we
review the pathophysiology of CPVT and discuss the role of sinus node dysfunction
as a modulator of arrhythmia risk and potential therapeutic target.
PMID- 25112806
TI - Resistance to rocuronium of rat diaphragm as compared with limb muscles.
AB - BACKGROUND: Skeletal muscles are composed of different muscle fiber types. We
investigated the different potency to rocuronium among diaphragm (DIA), extensor
digitorum longus (EDL), and soleus (SOL) in vitro as well as to investigate the
differences of acetylcholine receptors (AChRs) among these three typical kinds of
muscles. MATERIALS AND METHODS: The isolated left hemidiaphragm nerve-muscle
preparations, the EDL sciatic nerve-muscle preparations, and the SOL sciatic
nerve-muscle preparations were established to evaluate the potency to rocuronium.
Concentration-response curves were constructed and the values of IC50 were
obtained. The density of AChRs at the end plate and the number of AChRs per unit
fiber cross fiber area (CSA), AChR affinity for muscle relaxants were evaluated.
RESULTS: The concentration-twitch tension curves of rocuronium were significantly
different. The curves demonstrated a shift to the right of the DIA compared with
the EDL and SOL (P < 0.01), whereas no significant difference was observed
between EDL and SOL (P > 0.05). IC50 was significantly largest in DIA, second
largest in SOL, and smallest in EDL (P < 0.05). The number of AChRs per unit
fiber CSA was largest in DIA, second largest in EDL, and smallest in SOL (P <
0.01 or P < 0.05). The DIA showed the lowest affinity of the AChRs, whereas the
SOL showed the highest affinity. CONCLUSIONS: The resistance to rocuronium of DIA
compared with EDL and SOL was verified. The DIA was characterized by the largest
number of AChRs per unit fiber CSA and the lowest affinity of the AChRs. Although
compared with SOL, EDL was proved to have larger number of AChRs per unit fiber
CSA and the lower affinity of the AChRs. These findings may be the mechanisms of
different potency to rocuronium in DIA, EDL, and SOL. The results of the study
could help to explain the relationship between different composition of muscle
fibers and the potency to muscle relaxants. Extra caution should be taken in
clinical practice when monitoring muscle relaxation in anesthetic management
using different muscles.
PMID- 25112807
TI - Comparison of virtual bronchoscopy to fiber-optic bronchoscopy for assessment of
inhalation injury severity.
AB - PURPOSE: Compare virtual bronchoscopy (VB) to fiberoptic bronchoscopy (FOB) for
scoring smoke inhalation injury (SII). METHODS: Swine underwent computerized
tomography (CT) with VB and FOB before (0) and 24 and 48 h after SII. VB and FOB
images were scored by 5 providers off line. RESULTS: FOB and VB scores increased
over time (p<0.001) with FOB scoring higher than VB at 0 (0.30+/-0.79 vs. 0.03+/
0.17), 24 h (4.21+/-1.68 vs. 2.47+/-1.50), and 48h (4.55+/-1.83 vs. 1.94+/-1.29).
FOB and VB showed association with PaO2-to-FiO2 ratios (PFR) with areas under
receiver operating characteristic curves (ROC): for PFR<=300, VB 0.830, FOB
0.863; for PFR<=200, VB 0.794, FOB 0.825; for PFR<=100, VB 0.747, FOB 0.777 (all
p<0.001). FOB showed 80.3% specificity, 77% sensitivity, 88.8% negative
predictive value (NPV), and 62.3% positive-predictive value (PPV) for PFR<=300
and VB showed 67.2% specificity, 85.5% sensitivity, 91.3% NPV, and 53.4% PPV.
CONCLUSIONS: VB provided similar injury severity scores to FOB, correlated with
PFR, and reliably detected airway narrowing. VB performed during admission CT may
be a useful screening tool specifically to demonstrate airway narrowing induced
by SII.
PMID- 25112808
TI - Identification of drug-resistant subpopulations in canine hemangiosarcoma.
AB - Canine hemangiosarcoma is a rapidly progressive disease that is poorly responsive
to conventional chemotherapy. Despite numerous attempts to advance treatment
options and improve outcomes, drug resistance remains a hurdle to successful
therapy. To address this problem, we used recently characterized progenitor cell
populations derived from canine hemangiosarcoma cell lines and grown as non
adherent spheres to identify potential drug resistance mechanisms as well as drug
resistant cell populations. Cells from sphere-forming cultures displayed enhanced
resistance to chemotherapy drugs, expansion of dye-excluding side populations and
altered ATP-binding cassette (ABC) transporter expression. Invasion studies
demonstrated variability between cell lines as well as between sphere and
monolayer cell populations. Collectively, our results suggest that sphere cell
populations contain distinct subpopulations of drug-resistant cells that utilize
multiple mechanisms to evade cytotoxic drugs. Our approach represents a new tool
for the study of drug resistance in hemangiosarcoma, which could alter approaches
for treating this disease.
PMID- 25112809
TI - The influence of physiological noise correction on test-retest reliability of
resting-state functional connectivity.
AB - The utility and success of resting-state functional connectivity MRI (rs-fcMRI)
depend critically on the reliability of this technique and the extent to which it
accurately reflects neuronal function. One challenge is that rs-fcMRI is
influenced by various sources of noise, particularly cardiac- and respiratory
related signal variations. The goal of the current study was to evaluate the
impact of various physiological noise correction techniques, specifically those
that use independent cardiac and respiration measures, on the test-retest
reliability of rs-fcMRI. A group of 25 subjects were each scanned at three time
points--two within the same imaging session and another 2-3 months later.
Physiological noise corrections accounted for significant variance, particularly
in blood vessels, sagittal sinus, cerebrospinal fluid, and gray matter. The
fraction of variance explained by each of these corrections was highly similar
within subjects between sessions, but variable between subjects. Physiological
corrections generally reduced intrasubject (between-session) variability, but
also significantly reduced intersubject variability, and thus reduced the test
retest reliability of estimating individual differences in functional
connectivity. However, based on known nonneuronal mechanisms by which cardiac
pulsation and respiration can lead to MRI signal changes, and the observation
that the physiological noise itself is highly stable within individuals, removal
of this noise will likely increase the validity of measured connectivity
differences. Furthermore, removal of these fluctuations will lead to better
estimates of average or group maps of connectivity. It is therefore recommended
that studies apply physiological noise corrections but also be mindful of
potential correlations with measures of interest.
PMID- 25112811
TI - 8-year follow-up of central giant cell lesion mimicking apical periodontitis.
AB - INTRODUCTION: Lesions of nonendodontic origin may mimic apical periodontitis.
Central giant cell lesions (CGCLs) are aggressive or nonaggressive benign
idiopathic intraosseous lesions of the jaw. This report describes a case of a
CGCL in the periapical region of teeth #21-#26 of a 17-year-old female who sought
orthodontic care because of a change in the position of tooth #23. METHODS:
Clinical examination revealed mild facial asymmetry caused by increased volume in
the mental region and cortical bone expansion but no cortical disruption. A
panoramic radiograph showed a well-defined radiolucent osteolytic lesion
involving teeth #21-#26. The cortical bone was not affected, and there was no
root resorption. Incisional biopsy was performed, and the diagnosis was a CGCL.
The lesion was enucleated surgically. CGCLs should be included in the
differential diagnosis of jaw lesions that mimic apical periodontitis. RESULTS:
The patient subsequently underwent orthodontic treatment successfully.
CONCLUSIONS: The 8-year clinical and radiographic follow-up confirmed lesion
remission, no recurrence, and pulp vitality of all teeth.
PMID- 25112810
TI - Behavior of nickel-titanium instruments manufactured with different thermal
treatments.
AB - INTRODUCTION: The purpose of this study was to investigate if nickel-titanium
instruments with similar designs manufactured by different thermal treatments
would exhibit significantly different in vitro behavior. METHODS: Thirty-six
instruments each of ProTaper Universal (PTU F1; Dentsply Maillefer, Ballaigues,
Switzerland), ProFile Vortex (PV; Dentsply Tulsa Dental Specialties, Tulsa, OK),
Vortex Blue (VB, Dentsply Tulsa Dental Specialties), and TYPHOON Infinite Flex
NiTi (TYP; Clinician's Choice Dental Products, New Milford, CT) (all size 25/.06)
were evaluated. Bending resistance, torsion at failure, and dynamic torsional
tests were performed with the instruments (n = 12). Analysis of variance and
Tukey post hoc tests were applied. RESULTS: Flexibility was significantly higher
for TYP compared with the other 3 groups (P < .0001). With respect to the maximum
torque at failure, PV group showed the highest resistance to twisting (torsional
strength) among the analyzed instruments followed by VB, TYP, and PTU. The TYP
group exhibited greater angular deflection at failure compared with the other
groups (P < .0001). The mean dynamic torque scores during simulated canal
preparation were highest for TYP (3.01 +/- 0.71 Ncm) and lowest for PV (1.62 +/-
0.79 Ncm). However, no significant differences were observed comparing groups PTU
with TYP and VB and VB with PV (P > .05). The highest mean forces were recorded
with PTU (7.02 +/- 2.36 N) and the lowest with TYP (1.22 +/- 0.40 N).
CONCLUSIONS: TYP instruments were significantly more flexible than the other
instruments tested. The PV group had the highest torsional strength and TYP,
despite being the most flexible, showed similar torsional moments to the other
instruments, whereas its angular deflection was the highest among the groups.
PMID- 25112813
TI - Nasotracheal intubation with airway scope.
PMID- 25112812
TI - Predictors of hypofibrinogenemia in blunt trauma patients on admission.
AB - PURPOSE: Massive bleeding usually leads to critically low levels of clotting
factors, including fibrinogen. Although reduced fibrinogen levels correlate with
increased mortality, predictors of hypofibrinogenemia have remained poorly
understood. We investigated whether findings available on admission can be used
as predictors of hypofibrinogenemia. METHODS: We retrospectively reviewed serum
fibrinogen levels tested on arrival in 290 blunt trauma patients transported to a
level I trauma center during a 3-year period. The primary outcome was prehospital
predictors for hypofibrinogenemia. Covariates included age, sex, prehospital
fluid therapy, prehospital anatomical and physiological scores, time from injury,
base excess, and lactate on arrival. All variables with values of p < 0.10 in
univariate analysis were included in a multivariate logistic regression model.
The relationships between the variables and the 7-day mortality rate were
evaluated in a Cox proportional hazards model. RESULTS: Patient's age [odds ratio
(OR): 0.97, p < 0.001], Triage Revised Trauma Score (T-RTS) (OR: 0.81, p =
0.003), and prehospital fluid therapy (OR: 2.54, p = 0.01) were detected as
independent predictors for hypofibrinogenemia in multivariate logistic regression
analysis. Serum fibrinogen level [hazard ratio (HR): 0.99, p = 0.01] and T-RTS
(HR: 0.77, p < 0.01) were associated with the 7-day mortality rate. CONCLUSION: T
RTS is considered to play an important role in predicting hypofibrinogenemia and
7-day mortality in blunt trauma patients.
PMID- 25112814
TI - Signaling networks in MS: a systems-based approach to developing new
pharmacological therapies.
AB - The pathogenesis of multiple sclerosis (MS) involves alterations to multiple
pathways and processes, which represent a significant challenge for developing
more-effective therapies. Systems biology approaches that study pathway
dysregulation should offer benefits by integrating molecular networks and dynamic
models with current biological knowledge for understanding disease heterogeneity
and response to therapy. In MS, abnormalities have been identified in several
cytokine-signaling pathways, as well as those of other immune receptors. Among
the downstream molecules implicated are Jak/Stat, NF-Kb, ERK1/3, p38 or Jun/Fos.
Together, these data suggest that MS is likely to be associated with
abnormalities in apoptosis/cell death, microglia activation, blood-brain barrier
functioning, immune responses, cytokine production, and/or oxidative stress,
although which pathways contribute to the cascade of damage and can be modulated
remains an open question. While current MS drugs target some of these pathways,
others remain untouched. Here, we propose a pragmatic systems analysis approach
that involves the large-scale extraction of processes and pathways relevant to
MS. These data serve as a scaffold on which computational modeling can be
performed to identify disease subgroups based on the contribution of different
processes. Such an analysis, targeting these relevant MS-signaling pathways,
offers the opportunity to accelerate the development of novel individual or
combination therapies.
PMID- 25112815
TI - 'It feels like someone is hammering my feet': understanding pain and its
management from the perspective of people with multiple sclerosis.
AB - BACKGROUND: Pain affects around 63% of people with multiple sclerosis (pwMS).
Biomedical treatments demonstrate limited efficacy. More research is needed to
understand pain from the individual's perspective in order to better inform a
patient-centred approach that improves engagement, self-management and outcome.
OBJECTIVE: The objective of this paper is to explore pwMS' experience and
responses to pain, and their perspectives on pain management. METHODS: Twenty
five in-depth, semi-structured telephone interviews were conducted. Interviews
were audiotaped, transcribed and analysed using an inductive thematic analysis
approach with elements of grounded theory. RESULTS: Key themes included vivid
descriptions of pain and beliefs that pain is unpredictable, a sign of damage and
may worsen. Anger was a common emotional response. Two dominant pain management
themes emerged: one related to pain reduction and another to acceptance. Those
focusing on pain reduction appeared to engage in cycles in which they struggled
with symptoms and experienced continued distress. CONCLUSION: Findings identify
pain-related beliefs, emotional reactions and disparate pain-management
attitudes. All may influence pwMS' responses to pain and what they ask of their
clinicians. Uncovering pwMS' personal beliefs about pain, and introducing a
broader biopsychosocial understanding of pain in the clinical context, may
provide opportunities to rectify potentially unhelpful management choices and
enhance pain acceptance.
PMID- 25112816
TI - Factors associated with clinically significant increased walking time in multiple
sclerosis: results of a survival analysis of short-term follow-up data from a
clinical database.
AB - BACKGROUND: Because multiple sclerosis (MS) is variable and unpredictable, if
symptom worsening could be predicted, patients may feel better prepared to manage
changes in function. OBJECTIVE: The objective of this paper is to study the
prediction of walking impairment in MS. METHODS: We retrieved data for all MS
patients at our center (2008-2009), including baseline and follow-up timed 25
foot walk (T25FW) times. We assessed the incidence of >=20% worsening in T25FW by
developing two survival models: (1) disease course and (2) Multiple Sclerosis
Performance Scales (MSPS) score. The outcome was days until >=20% worsening in
T25FW. Covariates were disease subtype, years since diagnosis, Patient Health
Questionnaire-9 (PHQ-9) score, and demographics. Data were interval censored;
missing data were handled with multiple imputation. RESULTS: Of 1544 patients,
309 (20%) experienced >=20% worsening T25FW. For disease course, time to
worsening was significantly shorter for secondary progressive vs. relapsing
remitting disease (p < 0.001). For MSPS, patients with lower baseline MSPS scores
progressed more slowly (p = 0.001). In both models, sex, baseline T25W, and time
since diagnosis were significantly associated with worsening. In the disease
course model, PHQ 9 score may be related to worsening (p = 0.07). CONCLUSION:
These findings suggest factors associated with worsening in T25FW and a potential
approach to establishing indicators associated with clinically significant
change.
PMID- 25112817
TI - The effect of prolonged natalizumab treatment on anxiety and safety in JC virus
seropositive MS patients; a follow-up study.
PMID- 25112818
TI - Poor self-recognition of disordered eating among girls with bulimic-type eating
disorders: cause for concern?
AB - AIM: Bulimic-type eating disorders are common among young women and associated
with high levels of distress and disability and low uptake of mental health care.
We examined self-recognition of disordered eating and factors associated with
this among female adolescents with bulimic-type eating disorders (n = 139)
recruited from a large, population-based sample. METHODS: A vignette of a
fictional character with bulimia nervosa was presented, followed by a series of
questions addressing the nature and treatment of the problem described. One of
these questions required participants to indicate whether they currently had a
problem such as the one described. Self-report measures of eating disorder
symptoms, general psychological distress and quality of life were also completed.
RESULTS: More than half of participants (58%) did not believe that they currently
had a problem with their eating. In multivariable analysis, impairment in
emotional well-being and self-induced vomiting were the only variables
independently associated with self-recognition. Participants who recognized a
problem with their eating were more likely to have sought treatment for an eating
problem than those who did not. CONCLUSIONS: Recognition of disordered eating
among adolescents with bulimic-type eating disorders may be poor and this may be
a factor in low uptake of mental health care. Health promotion efforts may need
to address the misconception that only bulimic-type disorders involving self
induced vomiting are pathological.
PMID- 25112819
TI - Application of water footprint combined with a unified virtual crop pattern to
evaluate crop water productivity in grain production in China.
AB - Water shortages are detrimental to China's grain production while food production
consumes a great deal of water causing water crises and ecological impacts.
Increasing crop water productivity (CWP) is critical, so China is devoting
significant resources to develop water-saving agricultural systems based on crop
planning and agricultural water conservation planning. A comprehensive CWP index
is necessary for such planning. Existing indices such as water use efficiency
(WUE) and irrigation efficiency (IE) have limitations and are not suitable for
the comprehensive evaluation of CWP. The water footprint (WF) index, calculated
using effective precipitation and local water use, has advantages for CWP
evaluation. Due to regional differences in crop patterns making the CWP difficult
to compare directly across different regions, a unified virtual crop pattern is
needed to calculate the WF. This project calculated and compared the WF of each
grain crop and the integrated WFs of grain products with actual and virtual crop
patterns in different regions of China for 2010. The results showed that there
were significant differences for the WF among different crops in the same area or
among different areas for the same crop. Rice had the highest WF at 1.39 m(3)/kg,
while corn had the lowest at 0.91 m(3)/kg among the main grain crops. The WF of
grain products was 1.25 m(3)/kg in China. Crop patterns had an important impact
on WF of grain products because significant differences in WF were found between
actual and virtual crop patterns in each region. The CWP level can be determined
based on the WF of a virtual crop pattern, thereby helping optimize spatial
distribution of crops and develop agricultural water savings to increase CWP.
PMID- 25112820
TI - Asthma and asthma related symptoms in 23,326 Chinese children in relation to
indoor and outdoor environmental factors: the Seven Northeastern Cities (SNEC)
Study.
AB - BACKGROUND: Both the levels and patterns of outdoor and indoor air pollutants
have changed dramatically during the last decade in China. However, few studies
have evaluated the effects of the present air pollution on the health of Chinese
children. This study examines the association between outdoor and indoor air
pollution and respiratory diseases among children living in Liaoning, a heavy
industrial province of China. METHODS: A cross-sectional study of 23,326 Chinese
children aged 6 to 13 years was conducted in 25 districts of 7 cities in
Northeast China during 2009. Three-year (2006-2008) average concentrations of
particles with an aerodynamic diameter of <=10 MUm (PM10), sulfur dioxide (SO2),
nitrogen dioxides (NO2), and ozone (O3) were calculated from monitoring stations
in each of the 25 districts. We used two-level logistic regression models to
examine the effects of yearly variations in exposure to each pollutant,
controlling for important covariates. RESULTS: The prevalence of respiratory
symptoms was higher for those dwelling close to a busy road, those living near
smokestacks or factories, those living with smokers, those living in one-story
houses typically with small yards, and those with home renovation, bedroom carpet
or pets. Ventilation device use was associated with decreased odds of asthma in
children. The adjusted odds ratio for diagnosed-asthma was 1.34 (95% confidence
interval [CI], 1.24-1.45) per 31 MUg/m(3) increase in PM10, 1.23 (95%CI, 1.14
1.32) per 21 MUg/m(3) increase in SO2, 1.25 (95%CI, 1.16-1.36) per 10 MUg/m(3)
increase in NO2, and 1.31 (95%CI, 1.21-1.41) per 23 MUg/m(3) increase in O3,
respectively. CONCLUSION: Outdoor and indoor air pollution was associated with an
increased likelihood of respiratory morbidity among Chinese children.
PMID- 25112821
TI - Trace metal partitioning over a tidal cycle in an estuary affected by acid mine
drainage (Tinto estuary, SW Spain).
AB - The Tinto River estuary is highly polluted with the acid lixiviates from old
sulphide mines. In this work the behaviour of dissolved and particulate trace
metals under strong chemical gradients during a tidal cycle is studied. The pH
values range from 4.4 with low tide to 6.9 with high tide. Precipitation of Fe
and Al is intense during rising tides and As and Pb are almost exclusively found
in the particulate matter (PM). Sorption processes are very important in
controlling the mobility (and hence bioavailability) of some metals and
particularly affect Cu below pH 6. Above pH~6 Cu is desorbed, probably by the
formation of Cu(I)-chloride complexes. Although less pronounced than Cu, also Zn
desorption above pH 6.5 seems to occur. Mn and Co are affected by sorption
processes at pH higher than ca. 6. Cd behaves conservatively and Ni is slightly
affected by sorption processes.
PMID- 25112822
TI - Short-term bioavailability of carbon in soil organic matter fractions of
different particle sizes and densities in grassland ecosystems.
AB - The quality, stability and availability of organic carbon (OC) in soil organic
matter (SOM) can vary widely between differently managed ecosystems. Several
approaches have been developed for isolating SOM fractions to examine their
ecological roles, but links between the bioavailability of the OC of size-density
fractions and soil microbial communities have not been previously explored. Thus,
in the presented laboratory study we investigated the potential bioavailability
of OC and the structure of associated microbial communities in different particle
size and density fractions of SOM. For this we used samples from four grassland
ecosystems with contrasting management intensity regimes and two soil types: a
Haplic Cambisol and a typical Chernozem. A combined size-density fractionation
protocol was applied to separate clay-associated SOM fractions (CF1, <1 MUm; CF2,
1-2 MUm) from light SOM fractions (LF1, <1.8 g cm(-3); LF2, 1.8-2.0 g cm(-3)).
These fractions were used as carbon sources in a respiration experiment to
determine their potential bioavailability. Measured CO2-release was used as an
index of substrate accessibility and linked to the soil microbial community
structure, as determined by phospholipid fatty acids (PLFA) analysis. Several key
factors controlling decomposition processes, and thus the potential
bioavailability of OC, were identified: management intensity and the plant
community composition of the grasslands (both of which affect the chemical
composition and turnover of OC) and specific properties of individual SOM
fractions. The PLFA patterns highlighted differences in the composition of
microbial communities associated with the examined grasslands, and SOM fractions,
providing the first broad insights into their active microbial communities. From
observed interactions between abiotic and biotic factors affecting the
decomposition of SOM fractions we demonstrate that increasing management
intensity could enhance the potential bioavailability of OC, not only in the
active and intermediate SOM pools, but also in the passive pool.
PMID- 25112823
TI - Effects of olive oil wastes on river basins and an oligotrophic coastal marine
ecosystem: a case study in Greece.
AB - This work aims to contribute to the knowledge of the impacts of olive oil waste
discharge to freshwater and oligotrophic marine environments, since the
ecological impact of olive oil wastes in riverine and coastal marine ecosystems,
which are the final repositories of the pollutants, is a great environmental
problem on a global scale, mostly concerning all the Mediterranean countries with
olive oil production. Messinia, in southwestern Greece, is one of the greatest
olive oil production areas in Europe. During the last decade around 1.4*10(6)tons
of olive oil mill wastewater has been disposed in the rivers of Messinia and
finally entered the marine ecosystem of Messiniakos gulf. The pollution from
olive oil mill wastewater in the main rivers of Messinia and the oligotrophic
coastal zone of Messiniakos gulf and its effects on marine organisms were
evaluated, before, during and after the olive oil production period. Elevated
amounts of phenols (36.2-178 mg L(-1)) and high concentrations of ammonium (7.29
18.9 mmol L(-1)) and inorganic phosphorus (0.5-7.48 mmol L(-1)) were measured in
small streams where the liquid disposals from several olive oil industries were
gathered before their discharge in the major rivers of Messinia. The large number
of olive oil units has downgraded the riverine and marine ecosystems during the
productive period and a period more than five months is needed for the recovery
of the ecosystem. Statistical analysis showed that the enrichment of freshwater
and the coastal zone of Messiniakos gulf in ammonia, nitrite, phenols, total
organic carbon, copper, manganese and nickel was directly correlated with the
wastes from olive oil. Toxicity tests using 24h LC50 Palaemonidae shrimp confirm
that olive mill wastewater possesses very high toxicity in the aquatic
environment.
PMID- 25112824
TI - Serum regenerating islet-derived 3-alpha is a biomarker of mucosal enteropathies.
AB - BACKGROUND: The clinical presentation of organic and functional intestinal
disorders can overlap and clinicians often rely on invasive and time-consuming
procedures to make a final diagnosis. Regenerating islet-derived 3-alpha
(Reg3alpha) is detectable in the circulation of patients with intestinal graft
versus host disease and patients with inflammatory bowel disease (IBD). AIM: To
determine whether serum Reg3alpha testing is useful for discriminating mucosal
enteropathies from functional intestinal disorders. METHODS: We prospectively
included 47 patients with active coeliac disease (ACD), 13 patients with
refractory coeliac disease (RCD), seven patients with common variable
immunodeficiency (CVID), 72 patients with active Crohn's disease, 22 patients
with active ulcerative colitis (UC) and 28 patients with irritable bowel syndrome
(IBS)-related diarrhoea. Sera were also taken from 10 CD patients before and
after 6-12 months of a gluten-free diet (GFD) and from 14 patients with IBD
before and after induction therapy with Infliximab (IFX). Sera of 119 healthy
volunteers were used to determine the cut-off value. Reg3alpha levels were
measured by a commercial ELISA kit. RESULTS: Levels of Reg3alpha exceeded the cut
off value of the assay in 43/47(91%) ACD patients, 13/13(100%) RCD patients,
7/7(100%) CVID patients, 65/72(90%) Crohn's disease patients, 17/22(77%) UC
patients and one patient with IBS(4%). Reg3alpha levels distinguished mucosal
enteropathies from IBS with a sensitivity of 90% and a specificity of 96%.
Reg3alpha levels significantly decreased in CD patients following a GFD and in
IBD patients after treatment with IFX. CONCLUSION: Reg3alpha is a serum biomarker
of intestinal damage that, combined with clinical data, identifies patients who
should undergo invasive tests for diagnosing enteropathies.
PMID- 25112825
TI - Attending to the forest and the trees. Reply to comments on "Toward a
computational framework for cognitive biology: unifying approaches from cognitive
neuroscience and comparative cognition".
PMID- 25112826
TI - Complex networks are not (so much) privileged: comment on "approaching human
language with complex networks" by Cong and Liu.
PMID- 25112827
TI - Fanconi syndrome and severe polyuria: an uncommon clinicobiological presentation
of a Gitelman syndrome.
AB - BACKGROUND: Gitelman syndrome is an autosomal recessive tubulopathy characterized
by hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria. The
majority of patients do not present with symptoms until late childhood or
adulthood, and the symptoms are generally mild. We report here the first case of
Gitelman syndrome presenting with the biological features of Fanconi syndrome and
an early polyuria since the neonatal period. We discuss in this article the
atypical electrolytes losses found in our patient, as well as the possible
mechanisms of severe polyuria. CASE PRESENTATION: A 6-year-old Caucasian girl was
admitted via the Emergency department for vomiting, and initial laboratory
investigations found hyponatremia, hypokalemia, metabolic acidosis with normal
anion gap, hypophosphatemia, and hypouricemia. Urinalysis revealed Na, K, Ph and
uric acid losses. Thus, the initial biological profile was in favor of a proximal
tubular defect. However, etiological investigations were inconclusive and the
patient was discharged with potassium chloride and phosphorus supplementation.
Three weeks later, further laboratory analysis indicated persistent hypokalemia,
a metabolic alkalosis, hypomagnesemia, and hypocalciuria. We therefore sequenced
the SLC12A3 gene and found a compound heterozygosity for 2 known missense
mutations. CONCLUSIONS: Gitelman syndrome can have varying and sometimes atypical
presentations, and should be suspected in case of hypokalemic tubular disorders
that do not belong to any obvious syndromic entity. In this case, the proximal
tubular dysfunction could be secondary to the severe hypokalemia. This report
emphasizes the need for clinicians to repeat laboratory tests in undiagnosed
tubular disorders, especially not during decompensation episodes.
PMID- 25112830
TI - TRAF6 is a nexus for TLR-STAT1 crosstalk.
PMID- 25112829
TI - Protective genotypes in HIV infection reflect superior function of KIR3DS1+ over
KIR3DL1+ CD8+ T cells.
AB - Certain human class I histocompatibility-linked leukocyte antigen (HLA)/killer
cell immunoglobulin-like receptor (KIR) genotypic combinations confer more
favourable prognoses upon exposure to human immunodeficiency virus (HIV). These
combinations influence natural killer (NK) cell function, thereby implicating NK
cells in protection from HIV infection or disease progression. Because CD8(+) T
cells restrict HIV replication, depend upon HLA class I antigen presentation and
can also express KIR molecules, we investigated how these HLA/KIR combinations
relate to the phenotype and function of CD8(+) T cells from uninfected controls
and individuals with chronic HIV infection. CD8(+) T cells from KIR3DL1 and
KIR3DS1 homozygous individuals, and expressing the corresponding KIR, were
enumerated and phenotyped for CD127, CD57 and CD45RA expression. Ex vivo and in
vitro responsiveness to antigen-specific and polyclonal stimulation was compared
between KIR-expressing and non-expressing CD8(+) T cells by interferon-gamma
production. There were higher numbers and fractions of KIR3DL1-expressing CD8(+)
T cells in HIV-infected individuals independent of HLA-Bw4 co-expression, whereas
expansion of KIR3DS1-expressing CD8(+) T cells reflected HLA-Bw4*80I co
expression. KIR3DL1(+) and S1(+) CD8(+) T cells were predominantly CD127(
)CD57(+)CD45RA(+). KIR3DL1-expressing CD8(+) T cells were insensitive to ex vivo
stimulation with peptides from HIV or common viruses, but responded to anti-CD3
and recovered responsiveness to common viruses in vitro. Ex vivo non
responsiveness of KIR3DL1-expressing CD8(+) T cells was also independent of HLA
Bw4. KIR3DS1-expressing T cells responded normally to ex vivo antigenic
stimulation, illustrating functional superiority over KIR3DL1(+) CD8(+) T cells.
PMID- 25112832
TI - An innovative approach to providing collaborative education to undergraduate
students in the area of child maltreatment.
AB - Frontline workers in the area of child welfare often enter the field without
having taken any specialized coursework in the area of child maltreatment. This
article discusses an interdisciplinary certificate program that is specifically
designed to teach persons from various academic areas the knowledge and skills
necessary to work with children who experience maltreatment. The child advocacy
studies certificate program specifically focuses on coursework in the area of
child maltreatment and child advocacy to better train future frontline workers in
their vital roles. This certificate will decrease underreporting of child abuse
cases by mandated reporters by making them more aware of the signs and symptoms
of child maltreatment and also give students a greater understanding of how to
work with individuals from various fields.
PMID- 25112831
TI - The pREset Stent Retriever for Endovascular Treatment of Stroke Caused by MCA
Occlusion: Safety and Clinical Outcome.
AB - PURPOSE: The purpose of this study was to analyze the safety and efficacy of the
pREset device, a stent retriever system, for endovascular mechanical thrombectomy
(MT) in acute ischemic stroke (AIS) after middle cerebral artery (MCA) occlusion.
METHODS: Retrospectively, 48 consecutive patients (mean age +/- standard
deviation, 71.0 +/- 11.9 years; 24 women) treated for acute MCA occlusion using
pREset solely or in combination with other MT devices were identified.
Recanalization success was evaluated using the modified thrombolysis in cerebral
infarction score (TICI), and complications were detected by 24-h follow-up
computed tomography or magnetic resonance imaging. MCA anatomy was assessed in
angiograms. Clinical outcome was evaluated with National Institutes of Health
Stroke Scale (NIHSS) score at admission and discharge, and modified Rankin scale
(mRS) score at discharge and follow-up. RESULTS: Successful recanalization (TICI
2b/3) was achieved in 39 patients (81.3 %). Rate of procedure-related
complications was 8.3 %. In four patients, a subarachnoid hemorrhage occurred
(8.3 %), and parenchymal hematoma was detected in four patients (8.3 %). None of
those events was associated with clinical deterioration. MCA curvature
significantly influenced recanalization success (P < 0.005). Successful
recanalization correlated significantly with lower NIHSS scores and favorable
clinical outcome (mRS score 0-2) at discharge (P < 0.05). Mortality within 90
days was significantly lower in patients with TICI 2b/3 (P < 0.005). CONCLUSIONS:
High recanalization rates, low complication rates, and a significantly improved
outcome after successful recanalization strongly suggest that MT with pREset is
an adequate therapy for AIS after MCA occlusion. Vessel curvature is a
significant determining factor for recanalization success.
PMID- 25112833
TI - Perinatal exposure to bisphenol A exacerbates nonalcoholic steatohepatitis-like
phenotype in male rat offspring fed on a high-fat diet.
AB - Bisphenol A (BPA) is one of the environmental endocrine disrupting chemicals,
which is present ubiquitously in daily life. Accumulating evidence indicates that
exposure to BPA contributes to metabolic syndrome. In this study, we examined
whether perinatal exposure to BPA predisposed offspring to fatty liver disease:
the hepatic manifestation of metabolic syndrome. Wistar rats were exposed to 50
MUg/kg per day BPA or corn oil throughout gestation and lactation by oral gavage.
Offspring were fed a standard chow diet (SD) or a high-fat diet (HFD) after
weaning. Effects of BPA were assessed by examination of hepatic morphology,
biochemical analysis, and the hepatic expression of genes and/or proteins
involved in lipogenesis, fatty acid oxidation, gluconeogenesis, insulin
signaling, inflammation, and fibrosis. On a SD, the offspring of rats exposed to
BPA exhibited moderate hepatic steatosis and altered expression of insulin
signaling elements in the liver, but with normal liver function. On a HFD, the
offspring of rats exposed to BPA showed a nonalcoholic steatohepatitis-like
phenotype, characterized by extensive accumulation of lipids, large lipid
droplets, profound ballooning degeneration, impaired liver function, increased
inflammation, and even mild fibrosis in the liver. Perinatal exposure to BPA
worsened the hepatic damage caused by the HFD in the rat offspring. The additive
effects of BPA correlated with higher levels of hepatic oxidative stress.
Collectively, exposure to BPA may be a new risk factor for the development of
fatty liver disease and further studies should assess whether this finding is
also relevant to the human population.
PMID- 25112834
TI - Do patient-centered medical homes reduce emergency department visits?
AB - OBJECTIVE: To assess whether adoption of the patient-centered medical home (PCMH)
reduces emergency department (ED) utilization among patients with and without
chronic illness. DATA SOURCES: Data from approximately 460,000 Independence Blue
Cross patients enrolled in 280 primary care practices, all converting to PCMH
status between 2008 and 2012. RESEARCH DESIGN: We estimate the effect of a
practice becoming PCMH-certified on ED visits and costs using a difference-in
differences approach which exploits variation in the timing of PCMH
certification, employing either practice or patient fixed effects. We analyzed
patients with and without chronic illness across six chronic illness categories.
PRINCIPAL FINDINGS: Among chronically ill patients, transition to PCMH status was
associated with 5-8 percent reductions in ED utilization. This finding was robust
to a number of specifications, including analyzing avoidable and weekend ED
visits alone. The largest reductions in ED visits are concentrated among chronic
patients with diabetes and hypertension. CONCLUSIONS: Adoption of the PCMH model
was associated with lower ED utilization for chronically ill patients, but not
for those without chronic illness. The effectiveness of the PCMH model varies by
chronic condition. Analysis of weekend and avoidable ED visits suggests that
reductions in ED utilization stem from better management of chronic illness
rather than expanding access to primary care clinics.
PMID- 25112835
TI - Phylogenetic evidence for multiple intertypic recombinations in enterovirus B81
strains isolated in Tibet, China.
AB - Enterovirus B81 (EV-B81) is a newly identified serotype within the species
enterovirus B (EV-B). To date, only eight nucleotide sequences of EV-B81 have
been published and only one full-length genome sequence (the prototype strain)
has been made available in the GenBank database. Here, we report the full-length
genome sequences of two EV-B81 strains isolated in the Tibet Autonomous Region of
China during acute flaccid paralysis surveillance activities, and we also
conducted an antibody seroprevalence study in two prefectures of Tibet. The
sequence comparison and phylogenetic dendrogram analysis revealed high
variability among the global EV-B81 strains and frequent intertypic recombination
in the non-structural protein region of EV-B serotypes, suggesting high genetic
diversity of EV-B81. However, low positive rates and low titers of neutralizing
antibodies against EV-B81 were detected. Nearly 68% of children under the age of
five had no neutralizing antibodies against EV-B81. Hence, the extent of
transmission and the exposure of the population to this EV type are very limited.
Although little is known about the biological and pathogenic properties of EV-B81
because of few research in this field owing to the limited number of isolates,
our study provides basic information for further studies of EV-B81.
PMID- 25112838
TI - Halobacterium rubrum sp. nov., isolated from a marine solar saltern.
AB - Halophilic archaeal strain TGN-42-S1(T) was isolated from the Tanggu marine solar
saltern, China. Cells from strain TGN-42-S1(T) were observed to be pleomorphic
rods, stained Gram-negative, and formed red-pigmented colonies on solid media.
Strain TGN-42-S1(T) was found to be able to grow at 20-50 degrees C (optimum 35
37 degrees C), at 1.7-4.8 M NaCl (optimum 3.1 M), at 0-1.0 M MgCl2 (optimum 0.1
M), and at pH 5.0-9.0 (optimum pH 7.0-7.5). The cells lysed in distilled water,
and the minimal NaCl concentration to prevent cell-lysis was found to be 10 %
(w/v). The major polar lipids of the strain were phosphatidic acid,
phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester,
phosphatidylglycerol sulfate, galactosyl mannosyl glucosyl diether (TGD-1),
sulfated galactosyl mannosyl glucosyl diether (S-TGD-1), sulfated galactosyl
mannosyl galactofuranosyl glucosyl diether (S-TeGD), and three unidentified
glycolipids which were chromatographically identical to those of the
Halobacterium species. The 16S rRNA gene and rpoB' gene of strain TGN-42-S1(T)
were phylogenetically related to the corresponding genes of Halobacterium
jilantaiense CGMCC 1.5337(T) (98.8 and 93.5 % nucleotide identity, respectively),
Halobacterium salinarum CGMCC 1.1958(T) (98.4 and 91.9 %), and Halobacterium
noricense JCM 15102(T) (96.9 and 91.1 %). The DNA G + C content of strain TGN-42
S1(T) was determined to be 69.2 mol %. Strain TGN-42-S1(T) showed low DNA-DNA
relatedness with Hbt. jilantaiense CGMCC 1.5337(T) and Hbt. salinarum CGMCC
1.1958(T), the most closely related members of the genus Halobacterium. The
phenotypic, chemotaxonomic, and phylogenetic properties suggested that strain TGN
42-S1(T) (=CGMCC 1.12575(T) =JCM 19908(T)) represents a new species of
Halobacterium, for which the name Halobacterium rubrum sp. nov. is proposed.
PMID- 25112836
TI - Toll-like receptors in the pathogenesis of human B cell malignancies.
AB - Toll-like receptors (TLRs) are important players in B-cell activation, maturation
and memory and may be involved in the pathogenesis of B-cell lymphomas.
Accumulating studies show differential expression in this heterogeneous group of
cancers. Stimulation with TLR specific ligands, or agonists of their ligands,
leads to aberrant responses in the malignant B-cells. According to current data,
TLRs can be implicated in malignant transformation, tumor progression and immune
evasion processes. Most of the studies focused on multiple myeloma and chronic
lymphocytic leukemia, but in the last decade the putative role of TLRs in other
types of B-cell lymphomas has gained much interest. The aim of this review is to
discuss recent findings on the role of TLRs in normal B cell functioning and
their role in the pathogenesis of B-cell malignancies.
PMID- 25112839
TI - Basic fibroblastic growth factor affects the osteogenic differentiation of dental
pulp stem cells in a treatment-dependent manner.
AB - AIM: To determine how basic fibroblastic growth factor (bFGF) affected the
osteogenic differentiation of human dental pulp stem cells (DPSCs) in vitro and
in vivo. METHODOLOGY: Basic fibroblastic growth factor stimulation of DPSCs was
divided into a pre-treatment period and an osteogenic differentiation period.
Alizarin red quantification experiments and alkaline phosphatase activity
quantification assay were performed to examine the osteogenic differentiation of
DPSCs after different bFGF stimulation. Quantification reverse transcription
polymerase chain reaction was used to analyze the osteogenic gene expression of
DPSCs after different bFGF stimulation. In addition, DPSCs that received the 1
and 2 weeks bFGF pre-treatments as in the in vitro experiments were mineralized
for 1 week and seeded into hydroxyapatite/tricalcium phosphate (HA/TCP) pills and
subcutaneously transplanted into naked mice for 2 or 3 months. The transplants
were removed, sliced and stained using Modified Ponceau Trichrome Stain to
observe the formation of mineralized tissue. RESULTS: Basic fibroblastic growth
factor stimulation in the osteogenic differentiation period decreased the in
vitro osteogenic differentiation ability of DPSCs. One week pre-treatment with
bFGF increased the in vitro osteogenic differentiation ability of DPSCs, whereas
2 weeks pre-treatment with bFGF decreased the in vitro osteogenic differentiation
ability of DPSCs. The pre-treatment period was vital for the osteogenic
differentiation of DPSCs in vitro. The in vivo results were similar to the in
vitro results. CONCLUSIONS: Basic fibroblastic growth factor affected the
osteogenic differentiation of DPSCs in a treatment-dependent manner both in vitro
and in vivo.
PMID- 25112840
TI - Generalized regression neural network (GRNN)-based approach for colored dissolved
organic matter (CDOM) retrieval: case study of Connecticut River at Middle Haddam
Station, USA.
AB - The prediction of colored dissolved organic matter (CDOM) using artificial neural
network approaches has received little attention in the past few decades. In this
study, colored dissolved organic matter (CDOM) was modeled using generalized
regression neural network (GRNN) and multiple linear regression (MLR) models as a
function of Water temperature (TE), pH, specific conductance (SC), and turbidity
(TU). Evaluation of the prediction accuracy of the models is based on the root
mean square error (RMSE), mean absolute error (MAE), coefficient of correlation
(CC), and Willmott's index of agreement (d). The results indicated that GRNN can
be applied successfully for prediction of colored dissolved organic matter
(CDOM).
PMID- 25112841
TI - Potential effects of large linear pipeline construction on soil and vegetation in
ecologically fragile regions.
AB - Long-distance pipeline construction results in marked human disturbance of the
regional ecosystem and brings into question the safety of pipeline construction
with respect to the environment. Thus, the direct environmental impact and proper
handling of such large projects have received much attention. The potential
environmental effects, however, have not been fully addressed, particularly for
large linear pipeline projects, and the threshold of such effects is unclear. In
this study, two typical eco-fragile areas in western China, where large linear
construction projects have been conducted, were chosen as the case study areas.
Soil quality indices (SQI) and vegetation indices (VI), representing the most
important potential effects, were used to analyze the scope of the effect of
large pipeline construction on the surrounding environment. These two indices in
different buffer zones along the pipeline were compared against the background
values. The analysis resulted in three main findings. First, pipeline
construction continues to influence the nearby eco-environment even after a 4
year recovery period. During this period, the effect on vegetation due to
pipeline construction reaches 300 m beyond the working area, and is much larger
in distance than the effect on soil, which is mainly confined to within 30 m
either side of the pipeline, indicating that vegetation is more sensitive than
soil to this type of human disturbance. However, the effect may not reach beyond
500 m from the pipeline. Second, the scope of the effect in terms of distance on
vegetation may also be determined by the frequency of disturbance and the
intensity of the pipeline construction. The greater the number of pipelines in an
area, the higher the construction intensity and the more frequent the
disturbance. Frequent disturbance may expand the effect on vegetation on both
sides of the pipeline, but not on soil quality. Third, the construction may
eliminate the stable, resident plant community. During the recovery period, the
plant community in the work area of the pipeline is replaced by some species that
are rare or uncommon in the resident plant community because of human
disturbance, thereby increasing the plant diversity in the work area. In terms of
plant succession, the duration of the recovery period has a direct effect on the
composition and structure of the plant community. The findings provide a
theoretical basis and scientific foundation for improving the environmental
impact assessment (EIA) of oil and gas pipeline construction as it pertains to
the desert steppe ecosystem, and provide a reference point for recovery and
management of the eco-environment during the pipeline construction period.
PMID- 25112842
TI - Biological response to physical processes in the Indian Ocean sector of the
Southern Ocean: a case study in the coastal and oceanic waters.
AB - The spatial variation of chlorophyll a (Chl a) and factors influencing the high
Chl a were studied during austral summer based on the physical and biogeochemical
parameters collected near the coastal waters of Antarctica in 2010 and a zonal
section along 60 degrees S in 2011. In the coastal waters, high Chl a (>3 mg m(
3)) was observed near the upper layers (~15 m) between 53 degrees 30'E and 54
degrees 30'E. A comparatively higher mesozooplankton biomass (53.33 ml 100 m(-3))
was also observed concordant with the elevated Chl a. Low saline water formed by
melting of glacial ice and snow, as well as deep mixed-layer depth (60 m) due to
strong wind (>11 ms(-1)) could be the dominant factors for this biological
response. In the open ocean, moderately high surface Chl a was observed (>0.6 mg
m(-3)) between 47 degrees E and 50 degrees E along with a Deep Chlorophyll
Maximum of ~1 mg m(-3) present at 30-40 m depth. Melt water advected from the
Antarctic continent could be the prime reason for this high Chl a. The
mesozooplankton biomass (22.76 ml 100 m(-3)) observed in the open ocean was
comparatively lower than that in the coastal waters. Physical factors such as
melting, advection of melt water from Antarctic continent, water masses and wind
induced vertical mixing may be the possible reasons that led to the increase in
phytoplankton biomass (Chl a).
PMID- 25112843
TI - Two in one sweep: aluminum tolerance and grain yield in P-limited soils are
associated to the same genomic region in West African sorghum.
AB - BACKGROUND: Sorghum (Sorghum bicolor L. Moench) productivity is severely impeded
by low phosphorus (P) and aluminum (Al) toxic soils in sub-Saharan Africa and
especially West Africa (WA). Improving productivity of this staple crop under
these harsh conditions is crucial to improve food security and farmer's incomes
in WA. RESULTS: This is the first study to examine the genetics underlying
sorghum adaptation to phosphorus limitation in a wide range of WA growing
conditions. A set of 187 diverse sorghum genotypes were grown in 29 -P and + P
field experiments from 2006-2012 in three WA countries. Sorghum grain yield
performance under -P and + P conditions was highly correlated (r = 0.85***).
Significant genotype-by-phosphorus interaction was detected but with small
magnitude compared to the genotype variance component. We observed high genetic
diversity within our panel, with rapid linkage disequilibrium decay, confirming
recent sequence based studies in sorghum. Using genome wide association mapping
based on 220 934 SNPs we identified one genomic region on chromosome 3 that was
highly associated to grain yield production. A major Al-tolerance gene in
sorghum, SbMATE, was collocated in this region and SbMATE specific SNPs showed
very high associations to grain yield production, especially under -P conditions,
explaining up to 16% of the genotypic variance. CONCLUSION: The results suggest
that SbMATE has a possible pleiotropic role in providing tolerance to two of the
most serious abiotic stresses for sorghum in WA, Al toxicity and P deficiency.
The identified SNPs can help accelerate breeding for increased sorghum
productivity under unfavorable soil conditions and contribute to assuring food
security in WA.
PMID- 25112845
TI - Effect of sulodexide in patients with non-proliferative diabetic retinopathy:
diabetic retinopathy sulodexide study (DRESS).
AB - PURPOSE: To evaluate the effectiveness of sulodexide for the treatment of hard
exudates (HE) in non-proliferative diabetic retinopathy (NPDR). METHODS: This was
a randomized, placebo-controlled, multicenter trial involving 130 patients (65
for each group) who had mild-to-moderate NPDR with macular HE. Participants were
given a daily dose of either 50 mg sulodexide or a matching dose of placebo
orally for 12 months. Main outcome measure was an improvement in HE defined as a
decrease in severity by at least two grades on a 10-grade severity scale. This
was evaluated by fundus photography over 12-month period. RESULTS: The sulodexide
group showed significantly greater improvement in HE severity than that shown by
the placebo group (39.0 % vs. 19.3 %; chi square, P = 0.005). Logistic regression
analysis yielded an odds ratio of 2.790 (95 % confidence interval, 1.155-6.743; P
= 0.023) for the effect of treatment once adjustments were made for demographic,
prognostic and disease confounders. Intention to treat and per-protocol analysis
yielded similar results. Sulodexide's safety was comparable to that of the
placebo. CONCLUSIONS: Oral sulodexide therapy over 12 months improved macular HE
in patients with mild-to-moderate NPDR, without leading to detectable adverse
events. The study protocol was registered on clinicaltrial.gov under identifier
NCT01295775.
PMID- 25112848
TI - Pressure-driven ballistic Kelvin's water dropper for energy harvesting.
AB - In this paper, we introduce a microfluidic-based self-excited energy conversion
system inspired by Kelvin's water dropper but driven by inertia instead of
gravity. Two micro water jets are produced by forcing water through two
micropores by overpressure. The jets break up into microdroplets which are
inductively charged by electrostatic gates. The droplets land on metal targets
which are gradually charged up to high voltages. Targets and electrostatic gates
are cross-connected in a way similar to Kelvin's water dropper. Application of
pressure as driving force instead of gravity as in Kelvin's dropper allows for
much higher energy densities. To prevent overcharging of the droplets by the
inductive mechanism and consequent droplet loss by repulsion from the target as
in Kelvin's water dropper, a voltage divider using inversely connected diodes was
introduced in our system to control the charge induction providing self-limiting
positive feedback by the diode characteristics. A maximal 18% energy conversion
efficiency was obtained with the diode-gated system.
PMID- 25112847
TI - Changes of TGF-beta2, MMP-2, and TIMP-2 levels in the vitreous of patients with
high myopia.
AB - PURPOSE: To investigate the concentrations of transforming growth factor (TGF)
beta2, matrix metalloproteinase (MMP)-2, and tissue inhibitor of
metalloproteinase (TIMP)-2 in the vitreous of patients with high myopia. METHODS:
Twenty-six patients with high myopia (HM) who received vitrectomy for macular
retinoschisis or macular hole were enrolled in this prospective study. Twenty-six
patients with idiopathic macular hole or macular epiretinal membrane were chosen
as a control group. Vitreous samples were obtained during the vitrectomy surgery.
The levels of TGF-beta2,MMP-2,TIMP-2 in the vitreous samples were measured by
enzyme-linked immunosorbent assay. The MMP activity was determined by a
fluorometric assay. RESULTS: There was no significant difference in the vitreous
level of TGF-beta2 between HM (1.64 +/- 0.38 ng/ml) and the control group (1.56
+/- 0.32 ng/ml, p = 0.56). The vitreous levels of MMP-2 in HM (32.40 +/- 14.90
ng/ml) were significantly higher than in the control group (21.42 +/- 6.74 ng/ml,
p < 0.01). The ratio of MMP-2/TIMP-2 was significantly elevated in the vitreous
samples from HM (0.61 +/- 0.19), compared to the control group (0.48 +/- 0.11, p
< 0.05). The MMP activity was also significantly elevated in the vitreous samples
from HM (4,030.8 +/- 1,257.3 FIU), compared to the control group (3,245.8 +/-
835.6 FIU, p < 0.05). CONCLUSIONS: The elevated MMP/TIMP ratio and MMP activity
may play a role in the pathogenesis of human high myopia. Large prospective
studies are needed to further investigate the effect of MMPs in the pathogenesis
of human high myopia.
PMID- 25112850
TI - Clinical trials: Placebo effects in interstitial cystitis/bladder pain syndrome.
PMID- 25112846
TI - Investigation of blood flow regulation and oxygen saturation of the retinal
vessels in primary open-angle glaucoma.
AB - PURPOSE: To examine the supply of oxygen to the retina in primary open-angle
glaucoma (POAG). METHODS: Forty-one patients with primary open-angle glaucoma
(mean age 64.1 +/- 12.9 years) and 40 healthy subjects (63.6 +/- 14.1 years) were
included. Fundus images, centered at the optic disc, were taken using the Retinal
Vessel Analyzer (RVA). The vessel diameters were calculated as central retinal
artery (CRAE) and vein equivalent (CRVE) from diameter measurements in the
peripapillary vessels. The oxygen saturation of the arteries and veins was
investigated employing a two-wavelengths technique. After the measurement at
baseline, the vascular response to flicker light exposure was measured. RESULTS:
In glaucoma patients the mean oxygen saturation of the retinal veins at baseline
was higher than in the healthy controls (64.36 +/- 7.11 vs. 59.78 +/- 8.47, p =
0.01), whereas the mean arteriovenous oxygen saturation difference was lower
(33.07 +/- 5.24 vs. 37.53 +/- 6.95, p = 0.002). The arterial oxygen saturation as
well as the arterial and venous diameters showed no difference between the
groups. The increase of the CRVE during flicker light stimulation (3.72 +/- 3.29
% vs. 5.43 +/- 4.04, p = 0.039), as well as the change of the venous oxygen
saturation (2.08 +/- 3.74 % vs. 4.18 +/- 3.88 %, p = 0.016) and the arteriovenous
saturation difference (-2.1 +/- 3.31 % vs. -4.43 +/- 3.6 %, p = 0.003) were
smaller in POAG patients than in the healthy group. CONCLUSIONS: The reduction in
the arteriovenous difference in oxygen saturation in POAG patients might show a
decreased oxygen demand of the retina caused by the glaucomatous loss of
neuroretinal tissue. The lower extent of the flicker light-induced change of the
diameter of retinal veins and the venous oxygen saturation could indicate an
impairment of blood flow regulation.
PMID- 25112851
TI - Stones: Guidelines reignite interest in medical treatment of stones.
PMID- 25112853
TI - Prostate cancer: Probing progression in circulating tumour cells.
PMID- 25112854
TI - Beyond the G-spot: clitourethrovaginal complex anatomy in female orgasm.
AB - The search for the legendary, highly erogenous vaginal region, the Grafenberg
spot (G-spot), has produced important data, substantially improving understanding
of the complex anatomy and physiology of sexual responses in women. Modern
imaging techniques have enabled visualization of dynamic interactions of female
genitals during self-sexual stimulation or coitus. Although no single structure
consistent with a distinct G-spot has been identified, the vagina is not a
passive organ but a highly dynamic structure with an active role in sexual
arousal and intercourse. The anatomical relationships and dynamic interactions
between the clitoris, urethra, and anterior vaginal wall have led to the concept
of a clitourethrovaginal (CUV) complex, defining a variable, multifaceted
morphofunctional area that, when properly stimulated during penetration, could
induce orgasmic responses. Knowledge of the anatomy and physiology of the CUV
complex might help to avoid damage to its neural, muscular, and vascular
components during urological and gynaecological surgical procedures.
PMID- 25112857
TI - Prostate cancer: Is active surveillance safe for obese patients?
PMID- 25112858
TI - Surgery: Treating urotrauma--new guidelines to aid decisions.
PMID- 25112860
TI - Sexual dysfunction: A practical approach to men with premature ejaculation.
PMID- 25112861
TI - Prostate cancer: USPSTF screening recommendation could lead to greater numbers of
avoidable deaths.
PMID- 25112856
TI - Landmarks in the diagnosis and treatment of renal cell carcinoma.
AB - The most common renal cancer is renal cell carcinoma (RCC), which arises from the
renal parenchyma. The global incidence of RCC has increased over the past two
decades by 2% per year. RCC is the most lethal of the common urological cancers:
despite diagnostic advances, 20-30% of patients present with metastatic disease.
A clearer understanding of the genetic basis of RCC has led to immune-based and
targeted treatments for this chemoresistant cancer. Despite promising results in
advanced disease, overall response rates and durable complete responses are rare.
Surgery remains the main treatment modality, especially for organ-confined
disease, with a selective role in advanced and metastatic disease. Smaller
tumours are increasingly managed with biopsy, minimally invasive interventions
and surveillance. The future promises multimodal, integrated and personalized
care, with further understanding of the disease leading to new treatment options.
PMID- 25112862
TI - Halotriazolium axle functionalised [2]rotaxanes for anion recognition:
investigating the effects of halogen-bond donor and preorganisation.
AB - The anion-templated synthesis of three novel halogen-bonding 5-halo-1,2,3
triazolium axle containing [2]rotaxanes is described, and the effects of altering
the nature of the halogen-bond donor atom together with the degree of inter
component preorganisation on the anion-recognition properties of the interlocked
host investigated. The ability of the bromotriazolium motif to direct the halide
anion-templated assembly of interpenetrated [2]pseudorotaxanes was studied
initially; bromide was found to be the most effective template. As a consequence,
bromide anion templation was used to synthesise the first bromotriazolium axle
containing [2]rotaxane, the anion-binding properties of which, determined by (1)
H NMR spectroscopic titration experiments, revealed enhanced bromide and iodide
recognition relative to a hydrogen-bonding protic triazolium rotaxane analogue.
Two halogen-bonding [2]rotaxanes with bromo- and iodotriazolium motifs integrated
into shortened axles designed to increase inter-component preorganisation were
also synthesised. Anion (1) H NMR spectroscopic titration experiments
demonstrated that these rotaxanes were able to bind halide anions even more
strongly, with the iodotriazolium axle integrated rotaxane capable of recognising
halides in aqueous solvent media. Importantly, these observations suggest that a
halogen-bonding interlocked host binding domain, in combination with increased
inter-component preorganisation, are requisite design features for a potent anion
receptor.
PMID- 25112863
TI - Cause-specific mortality by race in low-income Black and White people with Type 2
diabetes.
AB - AIM: To investigate, with extended follow-up, cause-specific mortality among low
income Black and White Americans with Type 2 diabetes who have similar socio
economic status. METHODS: Black and White Americans aged 40-79 years with Type 2
diabetes (n = 12 498) were recruited from community health centres as part of the
Southern Community Cohort Study. Multivariable Cox analysis was used to estimate
mortality hazard ratios and 95% CIs for subsequent cause-specific mortality,
based on both underlying and contributing causes of death. RESULTS: During the
follow-up (median 5.9 years), 13.3% of the study population died. The leading
causes of death in each race were ischaemic heart disease, respiratory disorders,
cancer, renal failure and heart failure; however, Blacks were at a lower risk of
dying from ischaemic heart disease (hazard ratio 0.70, 95% CI 0.54-0.91) or
respiratory disorders (hazard ratio 0.70, 0.53-0.92) than Whites but had higher
or similar mortality attributable to renal failure (hazard ratio 1.57, 95% CI
1.02-2.40), heart failure (hazard ratio 1.47, 95% CI 0.98-2.19) and cancer
(hazard ratio 0.87, 95% CI 0.62-1.22). Risk factors for each cause of death were
generally similar in each race. CONCLUSIONS: These findings suggest that the
leading causes of death and their risk factors are largely similar among Black
and White Americans with diabetes. For the two leading causes of death in each
race, however, ischaemic heart disease and respiratory disorders, the magnitude
of risk is lower among Black Americans and contributes to their higher survival
rates.
PMID- 25112865
TI - Deferiprone in Friedreich ataxia: a 6-month randomized controlled trial.
AB - OBJECTIVE: We conducted a 6-month, randomized, double-blind, placebo-controlled
study to assess safety, tolerability, and efficacy of deferiprone in Friedreich
ataxia (FRDA). METHODS: Seventy-two patients were treated with deferiprone 20,
40, or 60mg/kg/day or placebo, divided into 2 daily doses. Safety was the primary
objective; secondary objectives included standardized neurological assessments
(Friedreich Ataxia Rating Scale [FARS], International Cooperative Ataxia Rating
Scale [ICARS], 9-Hole Peg Test [9HPT], Timed 25-Foot Walk, Low-Contrast Letter
Acuity), general functional status (Activities of Daily Living), and cardiac
assessments. RESULTS: Deferiprone was well tolerated at 20mg/kg/day, whereas more
adverse events occurred in the 40mg/kg/day than in the placebo group. The
60mg/kg/day dose was discontinued due to worsening of ataxia in 2 patients. One
patient on deferiprone 20mg/kg/day experienced reversible neutropenia, but none
developed agranulocytosis. Deferiprone-treated patients receiving 20 or
40mg/kg/day showed a decline in the left ventricular mass index, compared to an
increase in the placebo-treated patients. Patients receiving 20mg/kg/day of
deferiprone had no significant change in FARS, similar to the placebo-treated
patients, whereas those receiving 40mg/kg/day had worsening in FARS and ICARS
scores. The lack of deterioration in the placebo arm impaired the ability to
detect any potential protective effect of deferiprone. However, subgroup analyses
in patients with less severe disease suggested a benefit of deferiprone
20mg/kg/day on ICARS, FARS, kinetic function, and 9HPT. INTERPRETATION: This
study demonstrated an acceptable safety profile of deferiprone at 20mg/kg/day for
the treatment of patients with FRDA. Subgroup analyses raise the possibility
that, in patients with less severe disease, deferiprone 20mg/kg/day may reduce
disease progression, whereas higher doses appear to worsen ataxia.
PMID- 25112864
TI - Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of
transgenic mice.
AB - Alpha-synuclein (alpha-Syn) aggregates are the main component of Lewy bodies,
which are the characteristic pathological feature in Parkinson's disease (PD)
brain. Evidence that alpha-Syn aggregation can be propagated between neurones has
led to the suggestion that this mechanism is responsible for the stepwise
progression of PD pathology. Decreasing alpha-Syn expression is predicted to
attenuate this process and is thus an attractive approach to delay or halt PD
progression. We have used alpha-Syn small interfering RNA (siRNA) to reduce total
and aggregated alpha-Syn levels in mouse brains. To achieve widespread delivery
of siRNAs to the brain we have peripherally injected modified exosomes expressing
Ravies virus glycoprotein loaded with siRNA. Normal mice were analyzed 3 or 7
days after injection. To evaluate whether this approach can decrease alpha-Syn
aggregates, we repeated the treatment using transgenic mice expressing the human
phosphorylation-mimic S129D alpha-Syn, which exhibits aggregation. In normal mice
we detected significantly reduced alpha-Syn messenger RNA (mRNA) and protein
levels throughout the brain 3 and 7 days after treatment with RVG-exosomes loaded
with siRNA to alpha-Syn. In S129D alpha-Syn transgenic mice we found a decreased
alpha-Syn mRNA and protein levels throughout the brain 7 days after injection.
This resulted in significant reductions in intraneuronal protein aggregates,
including in dopaminergic neurones of the substantia nigra. This study highlights
the therapeutic potential of RVG-exosome delivery of siRNA to delay and reverse
brain alpha-Syn pathological conditions.
PMID- 25112867
TI - Evidence for a molecular diode-based mechanism in a multispecific ATP-binding
cassette (ABC) exporter: SER-1368 as a gatekeeping residue in the yeast multidrug
transporter Pdr5.
AB - ATP-binding cassette multidrug efflux pumps transport a wide range of substrates.
Current models suggest that a drug binds relatively tightly to a transport site
in the transmembrane domains when the protein is in the closed inward facing
conformation. Upon binding of ATP, the transporter can switch to an outward
facing (drug off or drug releasing) structure of lower affinity. ATP hydrolysis
is critically important for remodeling the drug-binding site to facilitate drug
release and to reset the transporter for a new transport cycle. We characterized
the novel phenotype of an S1368A mutant that lies in the putative drug-binding
pocket of the yeast multidrug transporter Pdr5. This substitution created broad,
severe drug hypersensitivity, although drug binding, ATP hydrolysis, and
intradomain signaling were indistinguishable from the wild-type control. Several
different rhodamine 6G efflux and accumulation assays yielded evidence consistent
with the possibility that Ser-1368 prevents reentry of the excluded drug.
PMID- 25112866
TI - Oligomeric state of purified transient receptor potential melastatin-1 (TRPM1), a
protein essential for dim light vision.
AB - Transient receptor potential melastatin-1 (TRPM1) is essential for the light
induced depolarization of retinal ON bipolar cells. TRPM1 likely forms a
multimeric channel complex, although almost nothing is known about the structure
or subunit composition of channels formed by TRPM1 or any of its close relatives.
Recombinant TRPM1 was robustly expressed in insect cells, but only a small
fraction was localized to the plasma membrane. Similar intracellular localization
was observed when TRPM1 was heterologously expressed in mammalian cells. TRPM1
was affinity-purified from Sf9 cells and complexed with amphipol, followed by
detergent removal. In blue native gels and size exclusion chromatography, TRPM1
migrated with a mobility consistent with detergent- or amphipol-bound dimers.
Cross-linking experiments were also consistent with a dimeric subunit
stoichiometry, and cryoelectron microscopy and single particle analysis without
symmetry imposition yielded a model with approximate 2-fold symmetrical features.
Finally, electron microscopy of TRPM1-antibody complexes revealed a large
particle that can accommodate TRPM1 and two antibody molecules. Taken together,
these data indicate that purified TRPM1 is mostly dimeric. The three-dimensional
structure of TRPM1 dimers is characterized by a small putative transmembrane
domain and a larger domain with a hollow cavity. Blue native gels of solubilized
mouse retina indicate that TRPM1 is present in two distinct complexes: one
similar in size to the recombinant protein and one much larger. Because dimers
are likely not functional ion channels, these results suggest that additional
partner subunits participate in forming the transduction channel required for dim
light vision and the ON pathway.
PMID- 25112869
TI - The role of constitutive nitric-oxide synthase in ultraviolet B light-induced
nuclear factor kappaB activity.
AB - NF-kappaB is a transcription factor involved in many signaling pathways that also
plays an important role in UV-induced skin tumorigenesis. UV radiation can
activate NF-kappaB, but the detailed mechanism remains unclear. In this study, we
provided evidence that the activation of constitutive nitric-oxide synthase plays
a role in regulation of IkappaB reduction and NF-kappaB activation in human
keratinocyte HaCaT cells in early phase (within 6 h) post-UVB. Treating the cells
with l-NAME, a selective inhibitor of constitutive nitric-oxide synthase (cNOS),
can partially reverse the IkappaB reduction and inhibit the DNA binding activity
as well as nuclear translocation of NF-kappaB after UVB radiation. A luciferase
reporter assay indicates that UVB-induced NF-kappaB activation is totally
diminished in cNOS null cells. The cNOS-mediated reduction of IkappaB is likely
due to the imbalance of nitric oxide/peroxynitrite because treating the cells
with lower (50 MUm), but not higher (100-500 MUm), concentration of S-nitroso-N
acetylpenicillamine (SNAP) can reverse the effect of l-NAME in partial restore
IkappaB level post-UVB. Our data also showed that NF-kappaB activity was required
for maintaining a stable IkappaB kinase alpha subunit (IKKalpha) level because
treating the cells with NF-kappaB or cNOS inhibitors could reduce IKKalpha level
upon UVB radiation. In addition, our data demonstrated that although NF-kappaB
protects cells from UVB-induced death, its pro-survival activity was likely
neutralized by the pro-death activity of peroxynitrite after UVB radiation.
PMID- 25112868
TI - Heme oxygenase-1 ameliorates dextran sulfate sodium-induced acute murine colitis
by regulating Th17/Treg cell balance.
AB - Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's
disease, is a group of autoimmune diseases characterized by nonspecific
inflammation in the gastrointestinal tract. Recent investigations suggest that
activation of Th17 cells and/or deficiency of regulatory T cells (Treg) is
involved in the pathogenesis of IBD. Heme oxygenase (HO)-1 is a protein with a
wide range of anti-inflammatory and immune regulatory function, which exerts
significantly protective roles in various T cell-mediated diseases. In this
study, we aim to explore the immunological regulation of HO-1 in the dextran
sulfate sodium-induced model of experimental murine colitis. BALB/c mice were
administered 4% dextran sulfate sodium orally; some mice were intraperitoneally
pretreated with HO-1 inducer hemin or HO-1 inhibitor stannum protoporphyrin IX.
The results show that hemin enhances the colonic expression of HO-1 and
significantly ameliorates the symptoms of colitis with improved histological
changes, accompanied by a decreased proportion of Th17 cells and increased number
of Tregs in mesenteric lymph node and spleen. Moreover, induction of HO-1 down
regulates retinoic acid-related orphan receptor gammat expression and IL-17A
levels, while promoting Treg-related forkhead box p3 (Foxp3) expression and IL-10
levels in colon. Further study in vitro revealed that up-regulated HO-1 switched
the naive T cells to Tregs when cultured under a Th17-inducing environment, which
involved in IL-6R blockade. Therefore, HO-1 may exhibit anti-inflammatory
activity in the murine model of acute experimental colitis via regulating the
balance between Th17 and Treg cells, thus providing a possible novel therapeutic
target in IBD.
PMID- 25112870
TI - Thrombin cleavage of osteopontin disrupts a pro-chemotactic sequence for
dendritic cells, which is compensated by the release of its pro-chemotactic C
terminal fragment.
AB - Thrombin cleavage alters the function of osteopontin (OPN) by exposing an
integrin binding site and releasing a chemotactic C-terminal fragment. Here, we
examined thrombin cleavage of OPN in the context of dendritic cell (DC) migration
to define its functional domains. Full-length OPN (OPN-FL), thrombin-cleaved N
terminal fragment (OPN-R), thrombin- and carboxypeptidase B2-double-cleaved N
terminal fragment (OPN-L), and C-terminal fragment (OPN-CTF) did not have
intrinsic chemotactic activity, but all potentiated CCL21-induced DC migration.
OPN-FL possessed the highest potency, whereas OPNRAA-FL had substantially less
activity, indicating the importance of RGD. We identified a conserved
(168)RSKSKKFRR(176) sequence on OPN-FL that spans the thrombin cleavage site, and
it demonstrated potent pro-chemotactic effects on CCL21-induced DC migration. OPN
FLR168A had reduced activity, and the double mutant OPNRAA-FLR168A had even lower
activity, indicating that these functional domains accounted for most of the pro
chemotactic activity of OPN-FL. OPN-CTF also possessed substantial pro
chemotactic activity, which was fully expressed upon thrombin cleavage and its
release from the intact protein, because OPN-CTF was substantially more active
than OPNRAA-FLR168A containing the OPN-CTF sequence within the intact protein.
OPN-R and OPN-L possessed similar potency, indicating that the newly exposed C
terminal SVVYGLR sequence in OPN-R was not involved in the pro-chemotactic
effect. OPN-FL and OPN-CTF did not directly bind to the CD44 standard form or
CD44v6. In conclusion, thrombin cleavage of OPN disrupts a pro-chemotactic
sequence in intact OPN, and its loss of pro-chemotactic activity is compensated
by the release of OPN-CTF, which assumes a new conformation and possesses
substantial activity in enhancing chemokine-induced migration of DCs.
PMID- 25112871
TI - Angiotensin type 2 receptor signaling in satellite cells potentiates skeletal
muscle regeneration.
AB - Patients with advanced congestive heart failure (CHF) or chronic kidney disease
(CKD) often have increased angiotensin II (Ang II) levels and cachexia. Ang II
infusion in rodents causes sustained skeletal muscle wasting and decreases muscle
regenerative potential through Ang II type 1 receptor (AT1R)-mediated signaling,
likely contributing to the development of cachexia in CHF and CKD. However, the
potential role of Ang II type 2 receptor (AT2R) signaling in skeletal muscle
physiology is unknown. We found that AT2R expression was increased robustly in
regenerating skeletal muscle after cardiotoxin (CTX)-induced muscle injury in
vivo and differentiating myoblasts in vitro, suggesting that the increase in AT2R
played an important role in regulating myoblast differentiation and muscle
regeneration. To determine the potential role of AT2R in muscle regeneration, we
infused C57BL/6 mice with the AT2R antagonist PD123319 during CTX-induced muscle
regeneration. PD123319 reduced the size of regenerating myofibers and expression
of the myoblast differentiation markers myogenin and embryonic myosin heavy
chain. On the other hand, AT2R agonist CGP42112 infusion potentiated CTX injury
induced myogenin and embryonic myosin heavy chain expression and increased the
size of regenerating myofibers. In cultured myoblasts, AT2R knockdown by siRNA
suppressed myoblast differentiation marker expression and myoblast
differentiation via up-regulation of phospho-ERK1/2, and ERK inhibitor treatment
completely blocked the effect of AT2R knockdown. These data indicate that AT2R
signaling positively regulates myoblast differentiation and potentiates skeletal
muscle regenerative potential, providing a new therapeutic target in wasting
disorders such as CHF and CKD.
PMID- 25112872
TI - Glutathionylation of the aquaporin-2 water channel: a novel post-translational
modification modulated by the oxidative stress.
AB - Aquaporin-2 (AQP2) is the vasopressin-regulated water channel that controls renal
water reabsorption and urine concentration. AQP2 undergoes different regulated
post-translational modifications, including phosphorylation and ubiquitylation,
which are fundamental for controlling AQP2 cellular localization, stability, and
function. The relationship between AQP2 and S-glutathionylation is of potential
interest because reactive oxygen species (ROS), produced under renal failure or
nephrotoxic drugs, may influence renal function as well as the expression and the
activity of different transporters and channels, including aquaporins. Here, we
show for the first time that AQP2 is subjected to S-glutathionylation in kidney
and in HEK-293 cells stably expressing AQP2. S-Glutathionylation is a redox
dependent post-translational modification controlling several signal transduction
pathways and displaying an acute effect on free cytosolic calcium concentration.
Interestingly, we found that in fresh kidney slices, the increased AQP2 S
glutathionylation correlated with tert-butyl hydroperoxide-induced ROS
generation. Moreover, we also found that cells expressing wild-type human calcium
sensing receptor (hCaSR-wt) and its gain of function (hCaSR-R990G; hCaSR-N124K)
had a significant decrease in AQP2 S-glutathionylation secondary to reduced ROS
levels and reduced basal intracellular calcium concentration compared with mock
cells. Together, these new findings provide fundamental insight into cell
biological aspects of AQP2 function and may be relevant to better understand and
explain pathological states characterized by an oxidative stress and AQP2
dependent water reabsorption disturbs.
PMID- 25112873
TI - Diacylglycerol kinase delta phosphorylates phosphatidylcholine-specific
phospholipase C-dependent, palmitic acid-containing diacylglycerol species in
response to high glucose levels.
AB - Decreased expression of diacylglycerol (DG) kinase (DGK) delta in skeletal
muscles is closely related to the pathogenesis of type 2 diabetes. To identify DG
species that are phosphorylated by DGKdelta in response to high glucose
stimulation, we investigated high glucose-dependent changes in phosphatidic acid
(PA) molecular species in mouse C2C12 myoblasts using a newly established liquid
chromatography/MS method. We found that the suppression of DGKdelta2 expression
by DGKdelta-specific siRNAs significantly inhibited glucose-dependent increases
in 30:0-, 32:0-, and 34:0-PA and moderately attenuated 30:1-, 32:1-, and 34:1-PA.
Moreover, overexpression of DGKdelta2 also enhanced the production of these PA
species. MS/MS analysis revealed that these PA species commonly contain palmitic
acid (16:0). D609, an inhibitor of phosphatidylcholine-specific phospholipase C
(PC-PLC), significantly inhibited the glucose-stimulated production of the
palmitic acid-containing PA species. Moreover, PC-PLC was co-immunoprecipitated
with DGKdelta2. These results strongly suggest that DGKdelta preferably
metabolizes palmitic acid-containing DG species supplied from the PC-PLC pathway,
but not arachidonic acid (20:4)-containing DG species derived from the
phosphatidylinositol turnover, in response to high glucose levels.
PMID- 25112875
TI - The roles of the RIIbeta linker and N-terminal cyclic nucleotide-binding domain
in determining the unique structures of the type IIbeta protein kinase A: a small
angle x-ray and neutron scattering study.
AB - Protein kinase A (PKA) is ubiquitously expressed and is responsible for
regulating many important cellular functions in response to changes in
intracellular cAMP concentrations. The PKA holoenzyme is a tetramer (R2:C2), with
a regulatory subunit homodimer (R2) that binds and inhibits two catalytic (C)
subunits; binding of cAMP to the regulatory subunit homodimer causes activation
of the catalytic subunits. Four different R subunit isoforms exist in mammalian
cells, and these confer different structural features, subcellular localization,
and biochemical properties upon the PKA holoenzymes they form. The holoenzyme
containing RIIbeta is structurally unique in that the type IIbeta holoenzyme is
much more compact than the free RIIbeta homodimer. We have used small angle x-ray
scattering and small angle neutron scattering to study the solution structure and
subunit organization of a holoenzyme containing an RIIbeta C-terminal deletion
mutant (RIIbeta(1-280)), which is missing the C-terminal cAMP-binding domain to
better understand the structural organization of the type IIbeta holoenzyme and
the RIIbeta domains that contribute to stabilizing the holoenzyme conformation.
Our results demonstrate that compaction of the type IIbeta holoenzyme does not
require the C-terminal cAMP-binding domain but rather involves large structural
rearrangements within the linker and N-terminal cyclic nucleotide-binding domain
of the RIIbeta homodimer. The structural rearrangements are significantly greater
than seen previously with RIIalpha and are likely to be important in mediating
short range and long range interdomain and intersubunit interactions that
uniquely regulate the activity of the type IIbeta isoform of PKA.
PMID- 25112874
TI - Chemotherapeutic drugs induce ATP release via caspase-gated pannexin-1 channels
and a caspase/pannexin-1-independent mechanism.
AB - Anti-tumor immune responses have been linked to the regulated release of ATP from
apoptotic cancer cells to engage P2 purinergic receptor signaling cascades in
nearby leukocytes. We used the Jurkat T cell acute lymphocytic leukemia model to
characterize the role of pannexin-1 (Panx1) channels in the release of
nucleotides during chemotherapeutic drug-induced apoptosis. Diverse pro-apoptotic
drugs, including topoisomerase II inhibitors, kinase inhibitors, and proteosome
inhibitors, induced functional activation of Panx1 channels via caspase-3
mediated cleavage of the Panx1 autoinhibitory C-terminal domain. The caspase
activated Panx1 channels mediated efflux of ATP, but also ADP and AMP, with the
latter two comprising >90% of the released adenine nucleotide pool as cells
transitioned from the early to late stages of apoptosis. Chemotherapeutic drugs
also activated an alternative caspase- and Panx1-independent pathway for ATP
release from Jurkat cells in the presence of benzyloxycarbonyl-VAD, a pan-caspase
inhibitor. Comparison of Panx1 levels indicated much higher expression in
leukemic T lymphocytes than in normal, untransformed T lymphoblasts. This
suggests that signaling roles for Panx1 may be amplified in leukemic leukocytes.
Together, these results identify chemotherapy-activated pannexin-1 channels and
ATP release as possible mediators of paracrine interaction between dying tumor
cells and the effector leukocytes that mediate immunogenic anti-tumor responses.
PMID- 25112876
TI - Identification of key residues determining isomerohydrolase activity of human
RPE65.
AB - RPE65 is the retinoid isomerohydrolase that converts all-trans-retinyl ester to
11-cis-retinol, a key reaction in the retinoid visual cycle. We have previously
reported that cone-dominant chicken RPE65 (cRPE65) shares 90% sequence identity
with human RPE65 (hRPE65) but exhibits substantially higher isomerohydrolase
activity than that of bovine RPE65 or hRPE65. In this study, we sought to
identify key residues responsible for the higher enzymatic activity of cRPE65.
Based on the amino acid sequence comparison of mammalian and other lower
vertebrates' RPE65, including cone-dominant chicken, 8 residues of hRPE65 were
separately replaced by their counterparts of cRPE65 using site-directed
mutagenesis. The enzymatic activities of cRPE65, hRPE65, and its mutants were
measured by in vitro isomerohydrolase activity assay, and the retinoid products
were analyzed by HPLC. Among the mutants analyzed, two single point mutants,
N170K and K297G, and a double mutant, N170K/K297G, of hRPE65 exhibited
significantly higher catalytic activity than WT hRPE65. Further, when an amino
terminal fragment (Met(1)-Arg(33)) of the N170K/K297G double mutant of hRPE65 was
replaced with the corresponding cRPE65 fragment, the isomerohydrolase activity
was further increased to a level similar to that of cRPE65. This finding
contributes to the understanding of the structural basis for isomerohydrolase
activity. This highly efficient human isomerohydrolase mutant can be used to
improve the efficacy of RPE65 gene therapy for retinal degeneration caused by
RPE65 mutations.
PMID- 25112877
TI - p53 is required for cisplatin-induced processing of the mitochondrial fusion
protein L-Opa1 that is mediated by the mitochondrial metallopeptidase Oma1 in
gynecologic cancers.
AB - Mitochondria are highly dynamic organelles, and mitochondrial fission is a
crucial step of apoptosis. Although Oma1 is believed to be responsible for long
form Opa1 (L-Opa1) processing during mitochondrial fragmentation, whether and how
Oma1 is involved in L-Opa1 processing and participates in the regulation of
chemoresistance is unknown. Chemosensitive and chemoresistant ovarian (OVCA) and
cervical (CECA) cancer cells were treated with cisplatin (CDDP). Mitochondrial
dynamics and protein contents were assessed by immunofluorescence and Western
blot, respectively. The requirements of Oma1 and p53 for CDDP-induced L-Opa1
processing, mitochondrial fragmentation, and apoptosis were examined by siRNA or
cDNA. CDDP induces L-Opa1 processing and mitochondrial fragmentation in
chemosensitive but not in chemoresistant cells. CDDP induced Oma1 40-kDa form
increases in OV2008 cells, not in C13* cells. Oma1 knockdown inhibited L-Opa1
processing, mitochondrial fragmentation, and apoptosis. Silencing p53 expression
attenuated the effects of CDDP in Oma1 (40 kDa) increase, L-Opa1 processing,
mitochondrial fragmentation, and apoptosis in chemosensitive OVCA cells, whereas
reconstitution of p53 in p53 mutant or null chemoresistant OVCA cells induced
Oma1 (40 kDa) increase, L-Opa1 processing, mitochondrial fragmentation, and
apoptosis irrespective of the presence of CDDP. Prohibitin 1 (Phb1) dissociates
from Opa1-Phb1 complex and binds phosphorylated p53 (serine 15) in response to
CDDP in chemosensitive but not chemoresistant CECA cells. These findings
demonstrate that (a) p53 and Oma1 mediate L-Opa1 processing, (b) mitochondrial
fragmentation is involved in CDDP-induced apoptosis in OVCA and CECA cells, and
(c) dysregulated mitochondrial dynamics may in part be involved in the
pathophysiology of CDDP resistance.
PMID- 25112879
TI - A revision of Metaleptobasis Calvert (Odonata: Coenagrionidae) with seven
synonymies and the description of eighteen new species from South America.
AB - Examination of over 1,400 specimens of the neotropical genus Metaleptobasis
Calvert, 1907, including primary types or paratypes of 18 of the 20 currently
available species names and large series of specimens including pairs in tandem
and copula, allowed me to unequivocally associate older names with species,
distinguish between specific and intraspecific variability, associate both sexes
for each species, and recognize the existence of female polymorphism. As a
result, seven names are found to be junior synonyms: Metaleptobasis mauritia
Williamson, 1915 junior synonym of M. bicornis (Selys, 1877), M. manicaria
Williamson, 1915 and M. fernandezi Racenis, 1955 junior synonyms of M. diceras
(Selys, 1877), M. westfalli Cumming, 1954 junior synonym of M. foreli Ris, 1915,
and M. tetragena Calvert, 1947, M. weibezahni Racenis, 1955, and M. incisula De
Marmels, 1989 junior synonyms of M. brysonima Williamson, 1915. Lectotypes are
designated for M. amazonica and Leptobasis diceras. Eighteen new species of
Metaleptobasis are described: M. brevicauda (Holotype ?, Peru, Huanuco Dep.,
Shapajilla, jungle, 11 v 1939, F. Woytkowski leg., in UMMZ); M. falcifera
(Holotype ?, Peru, Madre De Dios Dep., Pakitza, Reserved Zone, Manu National
Park, T2 to R2 to T1 to base camp, 11 degrees 55'48''S, 71 degrees 15'18''W, 250
m, 17 ix 1989, J.A. Louton leg., in USNM); M. furcifera (Holotype ?, Peru, Loreto
Dep., Iquitos, iii 1936, G.G. Klug leg., in BMNH); M. gabrielae (Holotype ?,
Peru, Loreto Dep., Tamshiyacu-Tahuayo Reserve, forest interior (4 degrees
23'40''S, 73 degrees 14'56''W), 27 vii 2009, T. Faasen leg., in RMNH); M.
guillermoi (Holotype ?, Peru, Loreto Dep., Yarinacocha, temporary forest stream
(8 degrees 17'S, 74 degrees 37'W, 145 m), 2 vi 1972, D.L. Pearson leg., in FSCA);
M. inermis (Holotype ?, Brazil, Para State, Jacareacanga, vii 1969, F.R. Barbosa
leg., in UMMZ); M. leniloba (Holotype ?, Peru, Loreto Dep., Pacaya-Samiria
National Reserve, Santa Luisa trail (5 degrees 15'S, 74 degrees 40'W), 10 vi
2008, C. Beatty, A. Cordero & J. Hoffmann leg., in FSCA); M. longicauda (Holotype
?, Brazil, Mato Grosso State, C. Teles Pires, Alto Tapajos, 1-31 viii 1956, Sick
leg., in MNRJ); M. orthogonia (Holotype ?, Peru, Loreto Dep., San Juan, Rio
Amazonas, near Iquitos, viii 1939, J. Schunke leg., in FSCA); M. paludicola
(Holotype ?, Peru, Loreto Dep., Tamshiyacu-Tahuayo Reserve, swamp, 4 degrees
23'49''S, 73 degrees 14'57''W, 27 ii 2009, T. Faasen leg., in RMNH); M. panguanae
(Holotype ?, Peru, Huanuco Dep., Biological Station Panguana, E side Rio
Yuyapichis, 9 degrees 37'S, 74 degrees 57'W, 6-17 iv 2003, H.J. & E.-G.
Burmeister leg., in ZSM); M. peltata (Holotype ?, Peru Loreto Dep., Tamshiyacu
Tahuayo Reserve, 4 degrees 21'22''S, 73 degrees 11'0''W, 19 ii 2010, T. Faasen
leg., in RMNH); M. prostrata (Holotype ?, Peru, Junin Dep., Satipo, v 1945, P.
Paprzycki leg., in UMMZ); M. silvicola (Holotype ?, Peru, Madre de Dios Dep.,
Explorer's Inn on Rio Tambopata, 30 km SW Puerto Maldonado, main trail, 1 viii
1979, M. Perkins & P. Donahue leg., in FSCA); M. spatulata (Holotype ?, Peru,
Huanuco Dep., 10 km N of Cucharas, confluence of Huallaga and Pacay rivers, viii
1954, F. Woytkowski leg., in UMMZ); M. tridentigera (Holotype ?, Brazil, Rondonia
State, Porto Velho, Area Abunan, T11 Aleatorio, 8 degrees 46'S, 63 degrees 54'W,
86 m, 16 v 2010, Nogueira & Mendes leg., in MZUSP); M. truncata (Holotype ?,
Brazil, Para State, Jacareacanga, xi 1969, F.R. Barbosa leg., in UMMZ); and M.
turbinata (Holotype ?, Peru, Loreto Dep., Tamshiyacu-Tahuayo Reserve, forest
swamp (4 degrees 24'18''S, 73 degrees 14'38''W), 25 ii 2010, T. Fassen leg., in
RMNH). Illustrations, keys, diagnoses, and distribution maps for all 31 currently
known species are provided. Phylogenetic relationships within the genus
Metaleptobasis are analyzed based on 33 adult morphological characters, including
the 31 currently described species of Metaleptobasis and eleven outgroup taxa of
other Coenagrionidae of the subfamily Teinobasinae. The cladistic analysis
recovered Metaleptobasis as monophyletic, and as sister group of Aceratobasis
Kennedy, a teinobasine genus some of the species of which possess an articulated
spur on base of male cercus. Hypothesized relationships among its species are
discussed.
PMID- 25112880
TI - Swedish Plectida (Nematoda). Part 4. The genus Leptolaimus de Man, 1876.
AB - Twelve known and nine new species of Leptolaimus are described from bottom
sediments collected in marine habitats of Sweden, including the Bothnian Sea and
Bothnian Bay, the Baltic Sea proper, Gullmarn Fjord and the Skagerrak. Three of
these species have been previously recorded in Sweden while nine are new records
for the Swedish fauna. The following known species are redescribed: Leptolaimus
papilliger de Man, 1876, L. cupulatus Lorenzen, 1972, L. danicus Jensen, 1978, L.
donsi (Allgen, 1946) comb. n., L. mixtus Lorenzen, 1972, L. pellucidus (Southern,
1914) comb. n., L. venustus Lorenzen, 1972, L. lorenzeni (Boucher & de Bovee,
1972) comb. n., L. alatus Vitiello, 1971, L. macer Lorenzen, 1972, L.
septempapillatus Platt, 1973, L. elegans (Schuurmans Stekhoven & De Coninck,
1933) Gerlach, 1958. Leptolaimus primus sp. n. is characterised by the 319-472 um
long body; rounded labial region continuous with body contour; cephalic setae 1.5
2.0 um long; amphid located 7.0-11.5 um from anterior end; first body pore
located 18.5-28.0 um from anterior end; lateral field originating 35 um from
anterior end; female without supplements, vagina without pars refringens, vulva
midventral; male without tubular and with four alveolar supplements, alveolar
supplements without sclerotized inner ring; spicules arcuate and 13.5-16.0 um
long. Leptolaimus secundus sp. n. is characterised by the 576-645 um long body;
rounded labial region continuous with body contour; cephalic setae 2.0 um long;
amphid located 6.5-7.0 um from anterior end; first body pore located 23.0-28.5 um
from anterior end; lateral field originating 18.0-23.0 um from anterior end;
female without supplements, vagina without pars refringens, vulva midventral;
male with single tubular and 9-15 alveolar supplements, tubular supplement weakly
arcuate with blunt tips, alveolar supplements with sclerotized lining; spicules
arcuate and 23.0-26.5 um long. Leptolaimus tertius sp. n. is characterised by the
576-579 um long body; rounded labial region continuous with body contour;
cephalic setae 2 um long; amphid located 4-5 um from anterior end; first body
pore located 21.0-23.5 um from anterior end; lateral field originating 26-29 um
from anterior end; male with four tubular and 7-10 alveolar supplements, tubular
supplements weakly arcuate with blunt tips, alveolar supplements with sclerotized
inner ring; spicules arcuate and 25-26 um long. Leptolaimus quartus sp. n. is
characterised by the 597-686 mm long body; rounded labial region continuous with
body contour; cephalic setae 2.0-3.5 um long; amphid located 5.0-7.0 um from
anterior end; first body pore located 23.5-27.0 um from anterior end; lateral
field originating 19.0-27.0 um from anterior end; male with three tubular and 8-9
alveolar supplements, tubular supplements straight with blunt expanded tips,
alveolar supplements with sclerotized inner ring; spicules arcuate and 23.0-25.0
um long. Leptolaimus quintus sp. n. is characterised by the 443-528 um long body;
rounded labial region continuous with body contour; cephalic setae 1.0-2.0 um
long; amphid located 7.0-10.0 um from anterior end; first body pore located 18.0
28.5 um from anterior end; lateral field originating 25.0-41.0 um from anterior
end; female with two tubular supplements (one just posterior to cardia and one in
front of anus), vagina without pars refringens, vulva right-sublateral; male with
8-10 tubular and without alveolar supplements, tubular supplements weakly arcuate
with anchor-like tips; spicules arcuate and 17.0-22.0 um long. Leptolaimus sextus
sp. n. is characterised by the 626-728 um long body; truncated labial region
offset from body contour; cephalic setae 1.5-2.0 um long; amphid located 8.0-12.0
um from anterior end; first body pore located 41.0-48.5 um from anterior end;
lateral field originating 28.0-41.0 um from anterior end; female without
supplements, vagina without pars refringens, vulva midventral; male with five
(rarely six) tubular and without alveolar supplements, tubular supplements weakly
S-shaped with bifid tips; spicules arcuate and 39.0-46.0 um long. Leptolaimus
septimus sp. n. is characterised by the 679-850 um long body; truncate labial
region offset from body contour; cephalic setae 2.5-3.5 um long; amphid located
8.5-11.5 um from anterior end; first body pore located 37.0-44.0 um from anterior
end; lateral field originating 26.5-37.0 um from anterior end; female without
supplements, vagina without pars refringens, vulva midventral; male with four
(rarely five) tubular and without alveolar supplements, tubular supplements
weakly S-shaped, with bifid or blunt tips; spicules arcuate and 31.0-33.5 um
long. Leptolaimus octavus sp. n. is characterised by the 541-638 um long body;
truncate labial region continuous with body contour; cephalic setae 1.5-2.0 um
long; amphid located 8.5-12.0 um from anterior end; first body pore located 31.5
41.0 um from anterior end; lateral field originating 26.0-40.0 um from anterior
end and expanding into bursa-like structures along the tail; female without
supplements, vagina without pars refringens, vulva midventral; male with four
tubular and without alveolar supplements, tubular supplements weakly S-shaped
with dentate tips; spicules arcuate and 30.0-31.5 um long. Leptolaimus nonus sp.
n. is characterised by the 403-633 um long body; rounded labial region continuous
with body contour; cephalic setae 1.5-3.0 um long; amphid located 8.0-10.0 um
from anterior end; first body pore located 16.5-29.0 um from anterior end;
lateral field originating 47.0-99.0 um from anterior end and expanding into bursa
like structures along the proximal part of the tail; female without supplements,
vagina with bacilliform pars refringens, vulva right-subventral; male with 4-5
tubular and without alveolar supplements, tubular supplements weakly arcuate with
dentate tips; spicules arcuate and 17.0-26.0 um long. The following
nomenclatorial changes are proposed: Eutelolaimus donsi Allgen, 1947 is
transferred to the genus Leptolaimus, as L. donsi (Allgen, 1947) comb. n.;
Halaphanolaimus cangionensis Gagarin & Nguyen Vu Thanh, 2007 is transferred to
the genus Leptolaimus, as L. cangionensis (Gagarin & Nguyen Vu Thanh, 2007) comb.
n.; Halaphanolaimus harpaga Boucher & de Bovee, 1972 is transferred to the genus
Leptolaimus, as L. harpaga (Boucher & de Bovee, 1972) comb. n.; Halaphanolaimus
lorenzeni Boucher & de Bovee, 1972 is transferred to the genus Leptolaimus, as L.
lorenzeni (Boucher & de Bovee, 1972) comb. n.; Halaphanolaimus pellucidus
Southern, 1914 is transferred to the genus Leptolaimus, as L. pellucidus
(Southern, 1914) comb. n.; Halaphanolaimus rivalis Gagarin & Nguyen Vu Thanh,
2007 is transferred to the genus Leptolaimus, as L. rivalis (Gagarin & Nguyen Vu
Thanh, 2007) comb. n.; Halaphanolaimus marinus Kamran, Nasira & Shahina, 2010 is
transferred to the genus Leptolaimus as L. marinus (Kamran, Nasira & Shahina,
2010) comb. n. and considered a junior synonym of Leptolaimus rivalis (Gagarin &
Nguyen Vu Thanh, 2007) comb. n.; Halaphanolaimus sergeevae Urkmez & Brennan, 2013
is transferred to the genus Leptolaimus as L. sergeevae (Urkmez & Brennan, 2013)
comb. n.; Leptolaimus vitielloi nom. nov. is proposed for Leptolaimus minutus
Vitiello, 1971 nec L. minutus (Schuurmans Stekhoven, 1942) comb. n.; Polylaimium
exile Cobb, 1920 is transferred to the genus Leptolaimus, as L. exilis (Cobb,
1920) comb. n. and is considered species inquirendae. A taxonomic review, tabular
compendium and identification key for species of the genus Leptolaimus are also
given.
PMID- 25112881
TI - An updated host-parasite catalogue of world Dryinidae (Hymenoptera:
Chrysidoidea).
AB - An updated host-parasite catalogue of world Dryinidae is presented. The catalogue
presents 1014 relationships between dryinids and their hosts checked in 84
countries of the world, including 38 new records.
PMID- 25112878
TI - Proline biosynthesis is required for endoplasmic reticulum stress tolerance in
Saccharomyces cerevisiae.
AB - The amino acid proline is uniquely involved in cellular processes that underlie
stress response in a variety of organisms. Proline is known to minimize protein
aggregation, but a detailed study of how proline impacts cell survival during
accumulation of misfolded proteins in the endoplasmic reticulum (ER) has not been
performed. To address this we examined in Saccharomyces cerevisiae the effect of
knocking out the PRO1, PRO2, and PRO3 genes responsible for proline biosynthesis.
The null mutants pro1, pro2, and pro3 were shown to have increased sensitivity to
ER stress relative to wild-type cells, which could be restored by proline or the
corresponding genetic complementation. Of these mutants, pro3 was the most
sensitive to tunicamycin and was rescued by anaerobic growth conditions or
reduced thiol reagents. The pro3 mutant cells have higher intracellular reactive
oxygen species, total glutathione, and a NADP(+)/NADPH ratio than wild-type cells
under limiting proline conditions. Depletion of proline biosynthesis also
inhibits the unfolded protein response (UPR) indicating proline protection
involves the UPR. To more broadly test the role of proline in ER stress,
increased proline biosynthesis was shown to partially rescue the ER stress
sensitivity of a hog1 null mutant in which the high osmolality pathway is
disrupted.
PMID- 25112882
TI - Outcomes of infrainguinal revascularizations with endovascular first strategy in
critical limb ischemia.
AB - PURPOSE: This study was designed to study the outcome of infrainguinal
revascularization in patients with critical limb ischemia (CLI) in an institution
with a preference towards endovascular intervention first in patients with poor
condition, unfavourable anatomy for surgery, no venous material for bypass, and
old age. METHODS: A prospective, observational cohort study was conducted between
May 2007 and May 2010 in patients presenting with CLI. At baseline, the optimal
treatment was selected, i.e., endovascular or surgical treatment. In case of
uncertainty about the preferred treatment, a multidisciplinary team (MDT) was
consulted. Primary endpoints were quality of life and functional status 6 and 12
months after initial intervention, assessed by the VascuQol and AMC Linear
Disability Score questionnaires, respectively. RESULTS: In total, 113 patients
were included; 86 had an endovascular intervention and 27 had surgery. During
follow-up, 41 % underwent an additional ipsilateral revascularisation procedure.
For the total population, and endovascular and surgery subgroups, the VascuQol
sum scores improved after 6 and 12 months (p < 0.01 for all outcomes) compared
with baseline. The functional status improved (p = 0.043) after 12 months
compared with baseline for the total population. Functional status of the surgery
subgroup improved significantly after 6 (p = 0.031) and 12 (p = 0.044) months,
but not that of the endovascular subgroup. CONCLUSIONS: Overall, the strategy of
performing endovascular treatment first in patients with poor condition,
unfavourable anatomy for surgery, no venous material for bypass, and old age has
comparable or even slightly better results compared with the BASIL trial and
other cohort studies. All vascular groups should discuss whether their treatment
strategy should be directed at treating CLI patients preferably endovascular
first and consider implementing an MDT to optimize patient outcomes.
PMID- 25112883
TI - Chemical renal denervation by vincristine: the role of the flow rate of delivery.
AB - PURPOSE: Vincristine has been proven promising regarding its safety and efficacy
for the renal artery denervation both in experimental models and in humans. The
aim of the study was to compare in an experimental model the efficacy of constant
versus random flow rate delivery of vincristine on renal sympathetic denervation.
METHODS: We used 10 juvenile Landrace swine. After the introduction of a 7F
sheath into the femoral artery, a guide wire was advanced into the distal part of
the renal artery. Then the first delivery balloon catheter, which delivers
vincristine in random flow rate, was advanced at the proximal part of the artery,
and the balloon was inflated in order to locally deliver vincristine to the media
of the renal artery. The process was repeated in the contralateral renal artery,
with the use of the double balloon catheter that delivers vincristine with a
constant flow rate. Euthanasia of the animals was performed at 28 days. All
sections were processed for histological and immunohistochemical analysis.
RESULTS: The delivery of vincristine with both catheters was successful and
uncomplicated. Immunohistochemistry showed that the mean number of intact nerves
in all sections was significantly lower in the group of vincristine delivered
with constant flow catheter compared to the group that the delivery was performed
in a random fashion. (1.48 +/- 0.37 vs. 1.70 +/- 0.41, p = 0.04). CONCLUSION:
Chemical renal denervation with vincristine by a constant flow rate catheter is
more effective compared to the denervation performed by a catheter that delivers
vincristine in a random fashion.
PMID- 25112884
TI - Neurotensin--regulated miR-133alpha is involved in proinflammatory signalling in
human colonic epithelial cells and in experimental colitis.
AB - OBJECTIVE: Neurotensin (NT) mediates colonic inflammation through its receptor
neurotensin receptor 1 (NTR1). NT stimulates miR-133alpha expression in colonic
epithelial cells. We investigated the role of miR-133alpha in NT-associated
colonic inflammation in vitro and in vivo. DESIGN: miR-133alpha and aftiphilin
(AFTPH) levels were measured by quantitative PCR. Antisense (as)-miR-133alpha was
administrated intracolonicaly prior to induction of 2, 4, 6-trinitrobenzene
sulfonic acid (TNBS)-induced colitis and dextran sodium sulfate (DSS)-induced
colitis. The effect of AFTPH was examined by gene silencing in vitro. RESULTS: NT
increased miR-133alpha levels in NCM-460 overexpressing NTR1 (NCM460-NTR1) and
HCT-116 cells. NT-induced p38, ERK1/2, c-Jun, and NF-kappaB activation, as well
as IL-6, IL-8 and IL-1beta messenger RNA (mRNA) expression in NCM-460-NTR1 cells
were reduced in miR-133alpha-silenced cells, while overexpression of miR-133alpha
reversed these effects. MiR-133alpha levels were increased in TNBS (2 day) and
DSS (5 day) colitis, while NTR1 deficient DSS-exposed mice had reduced miR
133alpha levels, compared to wild-type colitic mice. Intracolonic as-miR-133alpha
attenuated several parameters of colitis as well expression of proinflammatory
mediators in the colonic mucosa. In silico search coupled with qPCR identified
AFTPH as a downstream target of miR-133alpha, while NT decreased AFTPH expression
in NCM-460-NTR1 colonocytes. Gene silencing of AFTPH enhanced NT-induced
proinflammatory responses and AFTPH levels were downregulated in experimental
colitis. Levels of miR-133alpha were significantly upregulated, while AFTPH
levels were downregulated in colonic biopsies of patients with ulcerative colitis
compared to controls. CONCLUSIONS: NT-associated colitis and inflammatory
signalling are regulated by miR-133alpha-AFTPH interactions. Targeting of miR
133alpha or AFTPH may represent a novel therapeutic approach in inflammatory
bowel disease.
PMID- 25112885
TI - Interrupted imino-Nazarov cyclization of 1-aminopentadienyl cation and related
cascade process.
AB - Facile 4pi conrotatory imino-Nazarov cyclization of a 1-aminopentadienyl cation
generated from condensation an aldehyde and secondary aniline in the presence of
a catalytic amount of a Lewis acid has been developed. Silver(I)-catalyzed
intramolecular arene trapping of the resulting cyclic oxyallyl cation leads to
formation of tricyclic indoline-fused cyclopentanone. The use of lanthanide salts
allows transformation after the initial trapping to afford tetrahydroquinoline
fused cyclopentenone in a concise manner.
PMID- 25112886
TI - Hearing and age-related changes in the gray mouse lemur.
AB - In order to examine auditory thresholds and hearing sensitivity during aging in
the gray mouse lemur (Microcebus murinus), suggested to represent a model for
early primate evolution and Alzheimer research, we applied brainstem-evoked
response audiometry (BERA), traditionally used for screening hearing sensitivity
in human babies. To assess the effect of age, we determined auditory thresholds
in two age groups of adult mouse lemurs (young adults, 1-5 years; old adults, >=7
years) using clicks and tone pips. Auditory thresholds indicated frequency
sensitivity from 800 Hz to almost 50 kHz, covering the species tonal
communication range with fundamentals from about 8 to 40 kHz. The frequency of
best hearing at 7.9 kHz was slightly lower than that and coincided with the
dominant frequencies of communication signals of a predator. Aging shifted
auditory thresholds in the range between 2 and 50.4 kHz significantly by 12-27
dB. This mild presbyacusis, expressed in a drop of amplitudes of BERA signals,
but not discernible in latencies of responses, suggests a metabolic age-related
decrease potentially combined with an accompanying degeneration of the cochlear
nerve. Our findings on hearing range of this species support the hypothesis that
predation was a driving factor for the evolution of hearing in small ancestral
primates. Likewise, results provide the empirical basis for future approaches
trying to differentiate peripheral from central factors when studying Alzheimer's
disease-like pathologies in the aging brain.
PMID- 25112888
TI - The Neurostimulation Appropriateness Consensus Committee.
PMID- 25112887
TI - [Selective sentinel node biopsy in breast cancer with contralateral axillary
drainage].
PMID- 25112889
TI - The appropriate use of neurostimulation of the spinal cord and peripheral nervous
system for the treatment of chronic pain and ischemic diseases: the
Neuromodulation Appropriateness Consensus Committee.
AB - INTRODUCTION: The Neuromodulation Appropriateness Consensus Committee (NACC) of
the International Neuromodulation Society (INS) evaluated evidence regarding the
safety and efficacy of neurostimulation to treat chronic pain, chronic critical
limb ischemia, and refractory angina and recommended appropriate clinical
applications. METHODS: The NACC used literature reviews, expert opinion, clinical
experience, and individual research. Authors consulted the Practice Parameters
for the Use of Spinal Cord Stimulation in the Treatment of Neuropathic Pain
(2006), systematic reviews (1984 to 2013), and prospective and randomized
controlled trials (2005 to 2013) identified through PubMed, EMBASE, and Google
Scholar. RESULTS: Neurostimulation is relatively safe because of its minimally
invasive and reversible characteristics. Comparison with medical management is
difficult, as patients considered for neurostimulation have failed conservative
management. Unlike alternative therapies, neurostimulation is not associated with
medication-related side effects and has enduring effect. Device-related
complications are not uncommon; however, the incidence is becoming less frequent
as technology progresses and surgical skills improve. Randomized controlled
studies support the efficacy of spinal cord stimulation in treating failed back
surgery syndrome and complex regional pain syndrome. Similar studies of
neurostimulation for peripheral neuropathic pain, postamputation pain,
postherpetic neuralgia, and other causes of nerve injury are needed.
International guidelines recommend spinal cord stimulation to treat refractory
angina; other indications, such as congestive heart failure, are being
investigated. CONCLUSIONS: Appropriate neurostimulation is safe and effective in
some chronic pain conditions. Technological refinements and clinical evidence
will continue to expand its use. The NACC seeks to facilitate the efficacy and
safety of neurostimulation.
PMID- 25112890
TI - The appropriate use of neurostimulation: stimulation of the intracranial and
extracranial space and head for chronic pain. Neuromodulation Appropriateness
Consensus Committee.
AB - INTRODUCTION: The International Neuromodulation Society (INS) has identified a
need for evaluation and analysis of the practice of neurostimulation of the brain
and extracranial nerves of the head to treat chronic pain. METHODS: The INS board
of directors chose an expert panel, the Neuromodulation Appropriateness Consensus
Committee (NACC), to evaluate the peer-reviewed literature, current research, and
clinical experience and to give guidance for the appropriate use of these
methods. The literature searches involved key word searches in PubMed, EMBASE,
and Google Scholar dated 1970-2013, which were graded and evaluated by the
authors. RESULTS: The NACC found that evidence supports extracranial stimulation
for facial pain, migraine, and scalp pain but is limited for intracranial
neuromodulation. High cervical spinal cord stimulation is an evolving option for
facial pain. Intracranial neurostimulation may be an excellent option to treat
diseases of the nervous system, such as tremor and Parkinson's disease, and in
the future, potentially Alzheimer's disease and traumatic brain injury, but
current use of intracranial stimulation for pain should be seen as
investigational. CONCLUSIONS: The NACC concludes that extracranial nerve
stimulation should be considered in the algorithmic treatment of migraine and
other disorders of the head. We should strive to perfect targets outside the
cranium when treating pain, if at all possible.
PMID- 25112891
TI - The appropriate use of neurostimulation: avoidance and treatment of complications
of neurostimulation therapies for the treatment of chronic pain. Neuromodulation
Appropriateness Consensus Committee.
AB - INTRODUCTION: The International Neuromodulation Society (INS) has determined that
there is a need for guidance regarding safety and risk reduction for implantable
neurostimulation devices. The INS convened an international committee of experts
in the field to explore the evidence and clinical experience regarding safety,
risks, and steps to risk reduction to improve outcomes. METHODS: The
Neuromodulation Appropriateness Consensus Committee (NACC) reviewed the world
literature in English by searching MEDLINE, PubMed, and Google Scholar to
evaluate the evidence for ways to reduce risks of neurostimulation therapies.
This evidence, obtained from the relevant literature, and clinical experience
obtained from the convened consensus panel were used to make final
recommendations on improving safety and reducing risks. RESULTS: The NACC
determined that the ability to reduce risk associated with the use of
neurostimulation devices is a valuable goal and possible with best practice. The
NACC has recommended several practice modifications that will lead to improved
care. The NACC also sets out the minimum training standards necessary to become
an implanting physician. CONCLUSIONS: The NACC has identified the possibility of
improving patient care and safety through practice modification. We recommend
that all implanting physicians review this guidance and consider adapting their
practice accordingly.
PMID- 25112893
TI - Paraneoplastic pemphigus associated with metastatic lymphoepithelioma-like
carcinoma originating from the thyroid gland.
PMID- 25112892
TI - The appropriate use of neurostimulation: new and evolving neurostimulation
therapies and applicable treatment for chronic pain and selected disease states.
Neuromodulation Appropriateness Consensus Committee.
AB - INTRODUCTION: The International Neuromodulation Society (INS) has determined that
there is a need to provide an expert consensus that defines the appropriate use
of neuromodulation technologies for appropriate patients. The Neuromodulation
Appropriateness Consensus Committee (NACC) was formed to give guidance to current
practice and insight into future developments. METHODS: The INS executive board
selected members of the international scientific community to analyze scientific
evidence for current and future innovations and to use clinical experience to
fill in any gaps in information. The NACC used PubMed and Google Scholar to
obtain current evidence in the field and used clinical and research experience to
give a more complete picture of the innovations in the field. RESULTS: The NACC
has determined that currently approved neurostimulation techniques and
technologies have expanded our ability to treat patients in a more effective and
specific fashion. Despite these advances, the NACC has identified several
additional promising technologies and potential applications for neurostimulation
that could move this field forward and expand the applicability of
neuromodulation. CONCLUSIONS: The NACC concludes that the field of
neurostimulation is an evolving and rapidly changing one that will lead to
improved patient access, safety, and outcomes.
PMID- 25112894
TI - The role of postnatal neurogenesis in supporting remote memory and spatial metric
processing.
AB - In this study, we determined the contribution of juvenile neurogenesis to the
performance of mice on a remote memory for temporally based association task and
in a novelty based spatial pattern separation task. This was accomplished by
mating homozygous DNMT1-loxP mice with heterozygous GFAP-Cre mice and comparing
Cre+ (no postnatal neurogenesis) to Cre- (wild type) littermate offspring. The
results indicate that Cre+ mice are impaired relative to Cre- mice in the remote
memory for a temporal based association task and in a novelty based spatial
pattern separation task. These results support the temporal integration model of
Aimone et al., [(2006) Nat Neurosci 9:723-727] and provide further support for an
important role for postnatally born neurons in spatial pattern separation. In
contrast, Cre+ mice are not impaired relative to Cre- mice in an object-context
recognition task and a spatial location recognition task. These latter data
suggest that postnatally derived neurons in the dentate gyrus (DG) do not support
all spatial and object recognition functions of the DG.
PMID- 25112895
TI - Antioxidant, antimicrobial and antiproliferative activities of Anthemis palestina
essential oil.
AB - BACKGROUND: Anthemis palestina (Asteraceae) extends across the Mediterranean
region, southwest Asia and eastern Africa. Although traditionally used for
several applications, in vitro investigation of biological functions associated
with Anthemis palestina essential oil had never been reported. METHODS: The air
dried flowers of Anthemis palestina were subjected to hydrodistillation to yield
the oil. The antioxidant activity of the hydrodistilled oil was characterized
using various in vitro model systems such as DPPH, ferric-reducing antioxidant
power and hydroxyl radical scavenging activity. Antibacterial activity was tested
against six bacterial species, representing both Gram positive and Gram negative
bacteria. Antifungal activity was evaluated using three Candida species. The
minimum inhibitory concentration (MIC) for each examined microorganism was
determined using the microdilution method. The oil's antiproliferative effects
against eight human cancer cell lines were also studied and the lethal doses that
resulted in 50% reduction of cell viability (LD50) were determined. RESULTS: The
results indicate that the essential oil of Anthemis palestina exhibited
substantial antioxidant activities as demonstrated with DPPH, ferric reducing
antioxidant power, and hydroxyl radical scavenging activity. In addition, a broad
spectrum antibacterial activity of the oil was revealed with better
susceptibility of Gram positive bacteria towards the oil. The MIC values ranged
between 6-75 MUg/ml. Besides, the oil demonstrated a moderate inhibitory effect
on the three Candida species examined; with MIC values ranging between 48-95
MUg/ml. Potent cytotoxic activities, especially against HeLa cell line; with LD50
of 32 MUg/ml, BJAB cell line; with LD50 of 57 MUg/ml, and Caco-2 cell line; with
LD50 of 61 MUg/ml, were observed. CONCLUSION: The results obtained indicate high
potential of Anthemis palestina essential oil as bioactive oil, for nutraceutical
and medical applications, possessing antioxidant, antimicrobial and
antiproliferative activities.
PMID- 25112897
TI - History of corneal transplantation in Australia.
AB - Corneal transplantation is a triumph of modern ophthalmology. The possibility of
corneal transplantation was first raised in 1797 but a century passed before Zirm
achieved the first successful penetrating graft in 1905. Gibson reported the
first corneal graft in Australia from Brisbane in 1940 and English established
the first eye bank there a few years later. Corneal transplantation evolved
steadily over the twentieth century. In the second half of the century,
developments in microsurgery, including surgical materials such as monofilament
nylon and strong topical steroid drops, accounted for improvements in outcomes.
In 2013, approximately 1500 corneal transplants were done in Australia. Eye
banking has evolved to cope with the rising demands for donor corneas. Australian
corneal surgeons collaborated to establish and support the Australian Corneal
Graft Registry in 1985. It follows the outcomes of their surgery and has become
an important international resource for surgeons seeking further improvement with
the procedure.
PMID- 25112898
TI - Current management of hemophilia B: recommendations, complications and emerging
issues.
AB - Hemophilia B is a rare hereditary hemorrhagic disorder characterized by
deficiency of the clotting factor IX (FIX). Hemophilia B patients experience mild
to-severe bleeding complications according to the degree of FIX defect. The
mainstay of treatment of hemophilia B consists of replacement therapy and
nowadays several plasma-derived and recombinant FIX products are commercially
available. This article reviews the current management of hemophilia B patients
analyzing the results of the most important clinical trials. In addition, it will
focus on the more recent advances in the production of new FIX molecules aimed at
the improvement of the clinical management of such patients.
PMID- 25112896
TI - Sexual selection in true fruit flies (Diptera: Tephritidae): transcriptome and
experimental evidences for phytochemicals increasing male competitive ability.
AB - In male tephritid fruit flies of the genus Bactrocera, feeding on secondary plant
compounds (sensu lato male lures = methyl eugenol, raspberry ketone and
zingerone) increases male mating success. Ingested male lures alter the male
pheromonal blend, normally making it more attractive to females and this is
considered the primary mechanism for the enhanced mating success. However, the
male lures raspberry ketone and zingerone are known, across a diverse range of
other organisms, to be involved in increasing energy metabolism. If this also
occurs in Bactrocera, then this may represent an additional benefit to males as
courtship is metabolically expensive and lure feeding may increase a fly's short
term energy. We tested this hypothesis by performing comparative RNA-seq analysis
between zingerone-fed and unfed males of Bactrocera tryoni. We also carried out
behavioural assays with zingerone- and cuelure-fed males to test whether they
became more active. RNA-seq analysis revealed, in zingerone-fed flies, up
regulation of 3183 genes with homologues transcripts to those known to regulate
intermale aggression, pheromone synthesis, mating and accessory gland proteins,
along with significant enrichment of several energy metabolic pathways and gene
ontology terms. Behavioural assays show significant increases in locomotor
activity, weight reduction and successful mating after mounting; all
direct/indirect measures of increased activity. These results suggest that
feeding on lures leads to complex physiological changes, which result in more
competitive males. These results do not negate the pheromone effect, but do
strongly suggest that the phytochemical-induced sexual selection is governed by
both female preference and male competitive mechanisms.
PMID- 25112899
TI - "It takes a village": multilevel approaches to recruit African Americans and
their families for genetic research.
AB - One barrier to searching for novel mutations in African American families with
breast cancer is the challenge of effectively recruiting families-affected and
non-affected relatives-into genetic research studies. Using a community-based
participatory research (CBPR) orientation, we incorporated several evidence-based
approaches through an iterative fashion to recruit for a breast cancer genetic
epidemiology study in African Americans. Our combined methods allowed us to
successfully recruit 341 African American women (247 with breast cancer and 94
relatives without breast cancer) from 127 families. Twenty-nine percent of
participants were recruited through National Witness Project (NWP) sites, 11 %
came from in-person encounters by NWP members, 34 % from the Love Army of Women,
24 % from previous epidemiologic studies, and 2 % from a support group. In terms
of demographics, our varied recruitment methods/sources yielded samples of
African American women that differ in terms of several sociodemographic factors
such as education, smoking, and BMI, as well as family size. To successfully
recruit African American families into epidemiological research, investigators
should include community members in the recruitment processes, be flexible in the
adoption of multipronged, iterative methods, and provide clear communication
strategies about the underlying benefit to potential participants. Our results
enhance our understanding of potential benefits and challenges associated with
various recruitment methods. We offer a template for the design of future studies
and suggest that generalizability may be better achieved by using multipronged
approaches.
PMID- 25112900
TI - Risk factors for mortality in patients with bloodstream infections caused by
carbapenem-resistant Pseudomonas aeruginosa: clinical impact of bacterial
virulence and strains on outcome.
AB - The incidence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) bacteremia
has increased in recent years, and infections caused by CRPA result in higher
mortality than those caused by susceptible strains. This study was performed to
evaluate the risk factors for mortality and to study the impact of virulence
factors and bacterial strains on clinical outcomes in patients with CRPA
bacteremia. Data on 63 episodes of CRPA bacteremia that have occurred between
January 1, 2007, and December 31, 2009, in a teaching hospital (2000 beds) in
Seoul, Korea, were analyzed. The Acute Physiology and Chronic Health Evaluation
II (APACHE II) score at the time of CRPA bacteremia and the capacity of CRPA to
form biofilm were independent predictive factors for mortality in patients with
CRPA bacteremia. In addition, the biofilm-forming ability and elastase activity
of strains were correlated with APACHE II scores to measure the severity of
disease and estimate predicted mortality in the patients.
PMID- 25112901
TI - Real-time Leishmania genus master mix: a platform compatibility and stability
study.
AB - Performing diagnostics and vector-pathogen surveillance in austere environments
is challenging. On-site diagnostic/detection mitigates vector-borne disease
complications during military or humanitarian deployments to disease endemic
locals. The mobile molecular diagnostic platform, Joint Biological Agent
Identification and Diagnostic System (JBAIDS; BioFire Diagnostics Inc., Salt Lake
City, UT, USA), rapidly identifies biothreat pathogens. Although ideal for remote
diagnostics, the platform was validated for specific pathogens of insignificant
epidemiological consequence. Recognizing the JBAIDS's remote diagnostic/detection
versatility, we tested a Leishmania genus real-time PCR master mix validated for
use on the SmartCycler(r) (Cepheid, Sunnyvale, CA, USA) for concomitant use on
the JBAIDS. We evaluated assay sensitivity, precision, and specificity of one or
more Leishmania spp. on the JBAIDS and found that the JBAIDS produces superior
detection sensitivity and specificity compared to the SmartCycler(r). We also
examined the storage stability of a bulk lot preparation of the Leishmania genus
real-time PCR master mix on the SmartCycler(r) to ensure that long periods of
frozen storage that would translate to a field environment with the JBAIDS were
not detrimental to the reagent. We found that the bulk master mix maintains its
stability over a 13-month time period. Overall, these studies confirm JBAIDS's
versatility and demonstrate a streamlined assay development approach where
reagents are compatible with both platforms.
PMID- 25112903
TI - Polymorphism in NFKBIA gene is associated with recurrent acute rejections in
liver transplant recipients.
AB - The nuclear factor of kappa light polypeptide gene enhancer B-cells inhibitor
alpha (NFKBIA) gene encodes a member of the nuclear factor-kappa-B inhibitor
family. Polymorphisms in this gene might be associated with a susceptibility to
acute rejection episodes following liver transplantation, as they may cause an
increased activation level of the proinflammatory transcription factor nuclear
factor of kappa light polypeptide gene enhancer in B-cells (NFkappaB). The aim of
this study was to evaluate whether the NFKBIA polymorphisms -297 C/T (rs2233409),
-826 C/T (rs2233406) and 126 G/A (rs696) affect the incidence of acute liver
graft rejection. A total of 199 liver transplant recipients was analyzed, 100
without (NAR) and 99 with early acute rejection (AR). Thirty-two individuals with
multiple acute rejections (MAR) were analyzed as a subgroup of AR. Polymerase
chain reaction-allele specific restriction enzyme analysis (PCR-ASRA) and allele
specific hybridization with fluorescence resonance energy transfer (FRET) were
used for genotyping. We identified the genotype NFKBIA 126 AA (P = 0.002) as well
as the haplotype NFKBIA-126A-297T-826T (P = 0.002) as a potential risk factor for
the occurrence of recurrent acute rejections. Furthermore, we assessed an
association between the 126 A allele and susceptibility to recurrent acute
rejections (P = 0.027). Our data suggest that the NFKBIA 126 G/A polymorphism
might be potentially helpful to identify liver transplant recipients with an
increased susceptibility to develop recurrent acute rejections.
PMID- 25112902
TI - Carotid intima media thickness and other cardiovascular risk factors in children
with congenital adrenal hyperplasia.
AB - PURPOSE: Patients with congenital adrenal hyperplasia (CAH) are at increased risk
for cardiovascular disease due to many factors. The aim of this study is to
investigate the presence of dyslipidemia, insulin resistance, and subclinical
atherosclerosis as indicated by carotid intima media thickness in children with
congenital adrenal hyperplasia. METHODS: Thirty-two children with congenital
adrenal hyperplasia (3-17 years) were compared with 32 healthy controls. All
underwent anthropometric evaluation, measurement of fasting lipids, glucose,
insulin, oral glucose tolerance test (OGTT), homeostasis model assessment for
insulin resistance (HOMA-IR), and carotid intima media thickness (CIMT). RESULTS:
Fasting glucose, glucose at 30, 60, 90, and 120 min during OGTT were
significantly higher in patients. HOMA-IR was also significantly higher in
patients (p = 0.036). Patients had significantly higher CIMT (p = 0.003), and
higher systolic blood pressure. (p = 0.04). No significant difference existed in
lipid profile. Both systolic and diastolic blood pressures correlated with
treatment duration (p = 0.002, p = 0.043, respectively). CONCLUSION: Children
with CAH are at increased risk of insulin resistance, glucose intolerance, early
atherosclerosis, and cardiovascular disease. Screening of these patients at an
early age is recommended.
PMID- 25112905
TI - Canadian connective tissue society meeting schedule.
PMID- 25112904
TI - Purification of Chitinase enzymes from Bacillus subtilis bacteria TV-125,
investigation of kinetic properties and antifungal activity against Fusarium
culmorum.
AB - BACKGROUND: Chitin is the main structural component of cell walls of fungi,
exoskeletons of insects and other arthropods and shells of crustaceans. Chitinase
enzyme is capable of degrading chitin, and this enzyme can be used as a
biological fungicide against phytopathogenic fungi, as well as an insecticide
against insect pests. METHODS: In this study, 158 isolates, which were derived
from bacteria cultures isolated from leaves and root rhizospheres of certain
plants in Turkey, were selected after confirming that they are not
phytopathogenic based on the hypersensitivity test performed on tobacco; and
antifungal activity test was performed against Fusarium culmorum, which is a
pathogenic fungi that cause decomposition of roots of vegetables. Accordingly,
chitinase enzyme activity assay was performed on 31 isolates that have an
antifungal activity, and among them the isolate of Bacillus subtilis TV-125 was
selected, which has demonstrated the highest activity. RESULTS: Chitinase enzyme
was purified by using ammonium sulphate and DEAE-sephadex ion exchange
chromatography. Ammonium sulphate precipitation of chitinase enzyme from Bacillus
subtilis TV-125 isolate was performed at maximum range of 0-20%, and 28.4-fold
purification was obtained with a 13.4% of yield. Optimum activity of the purified
enzyme was observed at pH 4.0 and at 50 degrees C of temperature. In addition, it
was identified that Bacillus subtilis TV-125A isolate retains 42% of its activity
at 80 degrees C temperature. CONCLUSION: In the last phase of the study,
chitinase enzyme purified from Bacillus subtilis TV-125A was tested on four
fungal agents, although all the results were positive, it was particularly
effective on F. culmorum according to the findings.
PMID- 25112906
TI - Reactions of atomic hydrogen with formic acid and carbon monoxide in solid
parahydrogen I: Anomalous effect of temperature.
AB - Low-temperature condensed phase reactions of atomic hydrogen with closed-shell
molecules have been studied in rare gas matrices as a way to generate unstable
chemical intermediates and to study tunneling-driven chemistry. Although
parahydrogen (pH2) matrix isolation spectroscopy allows these reactions to be
studied equally well, little is known about the analogous reactions conducted in
a pH2 matrix host. In this study, we present Fourier transform infrared (FTIR)
spectroscopic studies of the 193 nm photoinduced chemistry of formic acid (HCOOH)
isolated in a pH2 matrix over the 1.7 to 4.3 K temperature range. Upon short-term
irradiation the HCOOH readily undergoes photolysis to yield CO, CO2, HOCO, HCO
and H atoms. Furthermore, after photolysis at 1.9 K tunneling reactions between
migrating H atoms and trapped HCOOH and CO continue to produce HOCO and HCO,
respectively. A series of postphotolysis kinetic experiments at 1.9 K with
varying photolysis conditions and initial HCOOH concentrations show the growth of
HOCO consistently follows single exponential (k = 4.9(7)x10(-3) min(-1)) growth
kinetics. The HCO growth kinetics is more complex displaying single exponential
growth under certain conditions, but also biexponential growth at elevated CO
concentrations and longer photolysis exposures. By varying the temperature after
photolysis, we show the H atom reaction kinetics qualitatively change at ~2.7 K;
the reaction that produces HOCO stops at higher temperatures and is only observed
at low temperature. We rationalize these results using a kinetic mechanism that
involves formation of an H...HCOOH prereactive complex. This study clearly
identifies anomalous temperature effects in the reaction kinetics of H atoms with
HCOOH and CO in solid pH2 that deserve further study and await full quantitative
theoretical modeling.
PMID- 25112907
TI - Restoration of the interfacial properties of lung surfactant with a newly
designed hydrocarbon/fluorocarbon lipid.
AB - Serum proteins, especially fibrinogen, inactivate the lung surfactant mixture by
adsorbing quickly and irreversibly to the alveolar air/aqueous interface. As a
consequence of the inactivation, the surfactant becomes dysfunctional, and
respiration cannot be maintained properly. Preventing the adsorption of surface
active serum proteins to the air/water interface is important because this
phenomenon causes fatal diseases such as acute respiratory distress syndrome
(ARDS). Although some treatments exist, improvements in synthetic surfactants
that can resist this inactivation are still expected. In this context, a novel
ion pair lipid (IPL, CF3(CF2)7SO3(-)(CH2CH3)3N(+)(CH2OCH2)10(CH2)15CH3) has been
designed and synthesized. This surfactant reduces the inhibitory effect of
fibrinogen by selectively interacting with DPPC (dipalmitoylphosphatidylcholine)
and mimicking some of the interfacial properties of the pulmonary surfactant
protein B (SP-B). Surface pressure-area isotherms and fluorescence microscopy
images demonstrate that IPL can mix and interact synergistically with DPPC due to
its unique molecular structure. Hysteresis behaviors of the monolayers, which are
composed of mixtures of DPPC and IPL at different molar ratios, indicate that
with increasing amounts of IPL, the lipid losses from the interface induced by
the presence of fibrinogen significantly decrease. It is also found that IPL is
able to adsorb to monolayers formed in the presence of fibrinogen, whereas
fibrinogen cannot penetrate the monolayers formed in the presence of IPL. These
results indicate that by mimicking some of the interfacial properties of SP-B,
this novel hybrid molecule is promising in terms of preventing fibrinogen
adsorption and therefore resisting surfactant inactivation.
PMID- 25112909
TI - Effect of hygroscopicity of the metal salt on the formation and air stability of
lyotropic liquid crystalline mesophases in hydrated salt-surfactant systems.
AB - It is known that alkali, transition metal and lanthanide salts can form lyotropic
liquid crystalline (LLC) mesophases with non-ionic surfactants (such as
CiH2i+1(OCH2CH2)jOH, denoted as CiEj). Here we combine several salt systems and
show that the percent deliquescence relative humidity (%DRH) value of a salt is
the determining parameter in the formation and stability of the mesophases and
that the other parameters are secondary and less significant. Accordingly, salts
can be divided into 3 categories: Type I salts (such as LiCl, LiBr, LiI, LiNO3,
LiClO4, CaCl2, Ca(NO3)2, MgCl2, and some transition metal nitrates) have low %DRH
and form stable salt-surfactant LLC mesophases in the presence of a small amount
of water, type II salts (such as some sodium and potassium salts) that are
moderately hygroscopic form disordered stable mesophases, and type III salts that
have high %DRH values, do not form stable LLC mesophases and leach out salt
crystals. To illustrate this effect, a large group of salts from alkali and
alkaline earth metals were investigated using XRD, POM, FTIR, and Raman
techniques. Among the different salts investigated in this study, the LiX (where
X is Cl(-), Br(-), I(-), NO3(-), and ClO4(-)) and CaX2 (X is Cl(-), and NO3(-))
salts were more prone to establish LLC mesophases because of their lower %DRH
values. The phase behavior with respect to concentration, stability, and thermal
behavior of Li(I) systems were investigated further. It is seen that the phase
transitions among different anions in the Li(I) systems follow the Hofmeister
series.
PMID- 25112908
TI - Relationships between molecular mobility, fibrillogenesis of collagen molecules,
and the inflammatory response: an experimental study in vitro and in vivo.
AB - This study was designed to investigate the in vitro adsorption and
fibrillogenesis of collagen on a surface with dynamic properties and to
investigate how this surface affected the inflammatory response in vivo.
Investigation of collagen-surface interactions is directly related to the control
of wound healing where collagen adsorption, fibrillization, deposition, and
maturation occur. ABA-type block copolymers, composed of polyrotaxane (which
possesses alpha-cyclodextrin threaded along poly(ethylene glycol)) and
hydrophobic terminal segments, were used to prepare mobile surfaces with
representative dynamic properties. Analyses using a quartz crystal microbalance
with dissipation monitoring (QCM-D) indicated that increasing the mobility of the
polymer on the surface led to the formation of a soft collagen layer. The
collagens in this layer had rearranged, leading to the formation of thicker
collagen fibrils by lateral aggregation. When a surface with a high molecular
mobility was subcutaneously implanted into rats, collagen rearrangement occurred
leading to suppression of macrophage recruitment at the interface and the
formation of a fibrotic capsule around the implant. These results suggest that
surface mobility on an implant is an important parameter for normal wound
healing.
PMID- 25112910
TI - Plasmonic response of DNA-assembled gold nanorods: effect of DNA linker length,
temperature and linker/nanoparticles ratio.
AB - Optical properties of gold nanorod (AuNR) particles self-assembled with DNA are
systematically investigated. The particles assembly is driven by specific base
pair recognition between single strand (ss) DNA linker and DNA anchored to AuNRs,
and it results in the distance- and morphology-dependent plasmonic coupling of
AuNRs. The longitudinal plasmon band is distinctly affected by tuning the length
of DNA linker, the temperature and linker/AuNRs ratio. We observed that the
increase of temperature enhances the interparticle interactions and leads to
clear distinguishable plasmonic signals between linker lengths up to 100 bases.
Both absorbance decrease and shift of the longitudinal plasmon allow for use of
AuNR for the DNA sensing applications.
PMID- 25112911
TI - Fabrication of mesoporous TiO2 membranes by a nanoparticle-modified polymeric sol
process.
AB - A straightforward synthesis of crack-free mesoporous titania membrane on a
macroporous support without intermediate layers by a nanoparticle-modified
polymeric sol-gel process is reported. TiO2 nanoparticle (Degussa P25) was
dispersed into the prepared sol to toughen the formed gel. This helped to avoid
the cracking of membrane during the drying and early stage of sintering,
particularly when the sol-gel transformation occurred on a substrate with an
uneven surface. The results of X-ray diffraction and Brunauer-Emmett-Teller
analyses show that the nanoparticle doping did not significantly affect the
particle size of TiO2 nanocrystals; however, it slightly broadened the pore size
distribution because it has a larger particle size compared to the prepared
materials. The sols with and without P25 nanoparticle were subsequently dip
coated on a support with average pore size of 150nm, thus formed a mesoporous
membrane layer after drying and sintering processes. An integrated, crack-free
mesoporous TiO2 membrane layer was obtained by this method, while the membrane
prepared with the original sol developed a few cracks. Further, the filtration
experiment showed that the prepared membrane had a high flux, and the membrane
with nanoparticle modification delivered better separation performance by
rejection of dextran.
PMID- 25112913
TI - Removal of oil from oil-in-saltwater emulsions by adsorption onto nano-alumina
functionalized with petroleum vacuum residue.
AB - Formation water from oilfields is one of the major environmental issues related
to the oil industry. This research investigated oil adsorption onto nanoparticles
of hydrophobic alumina and alumina nanoparticles functionalized with a petroleum
vacuum residue (VR) at 2 and 4wt% to reduce the amount of oil in oil-saltwater
emulsions at different pH values (5, 7 and 9). The initial concentration of crude
oil in water ranged from 100 to 500mg/L. The change in oil concentration after
adsorption was determined using a UV-vis spectrophotometer. The results indicated
that all of the systems performed more effectively at a pH of 7 and using Al/4VR
material. The oil adsorption was higher for neutral and acid systems compared
with basic ones, and it was improved by increasing the amount of VR on the
surface of the alumina. Additionally, the amount of NaCl adsorbed onto
nanoparticles was estimated for different mixtures. The adsorption equilibrium
and kinetics were evaluated using the Dubinin-Astakhov model, the Brunauer-Emmet
Teller model, and pseudo-first- and pseudo-second-order models, with a better
fitting to the Brunauer-Emmet-Teller model and pseudo-second-order model.
PMID- 25112912
TI - Structural characterization and electrocatalytic application of hemoglobin
immobilized in layered double hydroxides modified with hydroxyl functionalized
ionic liquid.
AB - Hemoglobin (Hb) was immobilized in Zn2Al-Layered Double Hydroxides (LDH) modified
with Hydroxyl Functionalized Ionic Liquid (HFIL) through adsorption and
coprecipitation method, respectively. Adsorption experiments showed that the
presence of HFIL could enhance the maximum protein loading. However, the Hb
loading through coprecipitation technique was far higher than that for
adsorption. The role of HFIL on the interaction between Hb and LDH was
investigated by XRD, FTIR, UV-vis and fluorescence spectroscopies. Although the
quaternary structure of Hb entrapped in HFIL-LDH through coprecipitation
technique (denoted as HFIL-LDH-Hbcop) might be altered slightly more than that in
LDH (LDH-Hbcop), its secondary structure and redox-active heme groups kept
intact. Morphologies of LDH-Hbcop and HFIL-LDH-Hbcop biohybrids were analyzed
through SEM and TEM images. The direct electrochemistry of the immobilized Hb
indicated that the coprecipitation bioelectrode performed better than that of the
corresponding adsorption one. Regardless of adsorption and coprecipitation, the
introduction of HFIL could distinctly promote the electron transport. Among all
bioelectrodes, HFIL-LDH-Hbcop/GCE displayed the best electrocatalytic activity
for H2O2 determination with a larger electroactive Hb percentage (6.76%), higher
sensitivity (40.63A/Mcm(2)) and lower detection limit (0.0054MUmol/L). So HFIL
LDH could effectively immobilize enzymes via coprecipitation technique, which had
potential applications in the fabrication of electrochemical biosensors.
PMID- 25112914
TI - Synthesis of magnetic core/shell carbon nanosphere supported manganese catalysts
for oxidation of organics in water by peroxymonosulfate.
AB - Magnetic separation is more cost-effective than conventional separation processes
in heterogeneous catalysis, especially for ultrafine nanoparticles. Magnetic
core/shell nanospheres (MCS, Fe3O4/carbon) were synthesized by a hydrothermal
method and their supported manganese oxide nanoparticles (Mn/MCS) were obtained
by redox reactions between MCS and potassium permanganate at a low temperature.
The materials were analyzed by a variety of characterization techniques such as
powder X-ray diffraction (XRD), field emission scanning electron microscopy
(FESEM), energy-dispersive X-ray spectrometer (EDS), Fourier transform infrared
spectroscopy (FTIR), thermogravimetric analysis (TGA) and N2
adsorption/desorption. The Mn/MCS catalysts were able to effectively activate
Oxone(r) for phenol degradation in aqueous solutions. Nitrogen treated MCS
supported Mn achieved 100% conversion within 120min. Kinetic studies showed that
phenol degradation over supported Mn catalysts follows the first order kinetics.
It was also found that the catalysts can be easily separated from the aqueous
solutions by an external magnetic field. The Oxone(r) activation mechanism by
Mn/MCS catalysts was discussed and sulfate radicals were suggested to be the
primary reactive species generated from peroxymonosulfate (PMS) for phenol
catalytic oxidation.
PMID- 25112915
TI - Synthesis, characterization, and cellular uptake of magnetic nanocarriers for
cancer drug delivery.
AB - HYPOTHESIS: The absence of targetability is the primary inadequacy of
conventional chemotherapy. Targeted drug delivery systems are conceptualized to
overcome this challenge. We have designed a targetable magnetic nanocarrier
consisting of a superparamagnetic iron oxide (SPIO) core and biocompatible and
biodegradable poly(sebacic anhydride)-block-methyl ether poly(ethylene glycol)
(PSA-mPEG) polymer shell. The idea is that this type of carriers should
facilitate the targeting of cancer cells. EXPERIMENTS: PSA-mPEG was synthesized
with poly-condensation and the in vitro degradation rate of the polymer was
monitored by gel permeation chromatography (GPC). The magnetic nanocarriers were
fabricated devoid of any surfactants and were capable of carrying high payload of
hydrophobic dye. The successful encapsulation of SPIO within the polymer shell
was confirmed by TEM. The results we obtained from measuring the size of SPIO
loaded in polymeric NPs (SPIO-PNP) by dynamic light scattering (DLS) and iron
content measurement of these particles by ICP-MS, indicate that SPIO is the most
suitable carrier for cancer drug delivery applications. FINDINGS: Measuring the
hydrodynamic radii of SPIO-PNPs by DLS over one month revealed the high stability
of these particles at both body and room temperature. We further investigated the
cell viability and cellular uptake of SPIO-PNPs in vitro with MDA-MB-231 breast
cancer cells. We found that SPIO-PNPs induce negligible toxicity within a
concentration range of 1-2MUg/ml. The TEM micrographs of thin cross-sectioned MDA
MBA-231 cells showed internalization of SPIO-PNPs within size range of 150-200nm
after 24h. This study has provided a foundation for eventually loading these
nanoparticles with anti-cancer drugs for targeted cancer therapy using an
external magnetic field.
PMID- 25112916
TI - Self-assembly of flagellin on Au(111) surfaces.
AB - The adsorption of flagellin monomers from Pseudomonas fluorescens on Au(111) has
been studied by Atomic Force Microscopy (AFM), Scanning Tunneling Microscopy
(STM), X-ray Photoelectron Spectroscopy (XPS), Surface Plasmon Resonance (SPR),
and electrochemical techniques. Results show that flagellin monomers
spontaneously self-assemble forming a monolayer thick protein film bounded to the
Au surface by the more hydrophobic subunit and exposed to the environment the
hydrophilic subunit. The films are conductive and allow allocation of
electrochemically active cytochrome C. The self-assembled films could be used as
biological platforms to build 3D complex molecular structures on planar metal
surfaces and to functionalize metal nanoparticles.
PMID- 25112918
TI - Ultrasensitive electrochemical biosensor for detection of DNA from Bacillus
subtilis by coupling target-induced strand displacement and nicking endonuclease
signal amplification.
AB - A simple, ultrasensitive, and specific electrochemical biosensor was designed to
determine the given DNA sequence of Bacillus subtilis by coupling target-induced
strand displacement and nicking endonuclease signal amplification. The target DNA
(TD, the DNA sequence from the hypervarient region of 16S rDNA of Bacillus
subtilis) could be detected by the differential pulse voltammetry (DPV) in a
range from 0.1 fM to 20 fM with the detection limit down to 0.08 fM at the
3s(blank) level. This electrochemical biosensor exhibits high distinction ability
to single-base mismatch, double-bases mismatch, and noncomplementary DNA
sequence, which may be expected to detect single-base mismatch and single
nucleotide polymorphisms (SNPs). Moreover, the applicability of the designed
biosensor for detecting the given DNA sequence from Bacillus subtilis was
investigated. The result obtained by electrochemical method is approximately
consistent with that by a real-time quantitative polymerase chain reaction
detecting system (QPCR) with SYBR Green.
PMID- 25112917
TI - Chars from gasification of coal and pine activated with K2CO3: acetaminophen and
caffeine adsorption from aqueous solutions.
AB - The high carbon contents and low toxicity levels of chars from coal and pine
gasification provide an incentive to consider their use as precursors of porous
carbons obtained by chemical activation with K2CO3. Given the chars
characteristics, previous demineralization and thermal treatments were made, but
no improvement on the solids properties was observed. The highest porosity
development was obtained with the biomass derived char (Pi). This char sample
produced porous materials with preparation yields near 50% along with high
porosity development (ABET~1500m(2)g(-1)). For calcinations at 800 degrees C, the
control of the experimental conditions allowed the preparation of samples with a
micropore system formed almost exclusively by larger micropores. A mesopore
network was developed only for samples calcined at 900 degrees C. Kinetic and
equilibrium acetaminophen and caffeine adsorption data, showed that the processes
obey to a pseudo-second order kinetic equation and to the Langmuir model,
respectively. The results of sample Pi/1:3/800/2 outperformed those of the
commercial carbons. Acetaminophen adsorption process was ruled by the micropore
size distribution of the carbons. The caffeine monolayer capacities suggest a
very efficient packing of this molecule in samples presenting monomodal micropore
size distribution. The surface chemistry seems to be the determinant factor that
controls the affinity of caffeine towards the carbons.
PMID- 25112919
TI - HOMA-IR and the risk of hyperuricemia: a prospective study in non-diabetic
Japanese men.
AB - AIMS: To examine the relation of insulin resistant status determined by
homeostasis model assessment of insulin resistance (HOMA-IR) with the risk of
incident hyperuricemia. METHODS: The study participants included 2071 Japanese
men without hyperuricemia and diabetes, aged 35-54 years. The participants had
undergone annual heath examinations for 6 years to compare incident hyperuricemia
(serum uric acid >416.4MUmol/L (7.0mg/dL) and/or taking medication for
hyperuricemia) in four groups based on quartiles of baseline HOMA-IR. RESULTS:
During follow-up there were 331 incident cases of hyperuricemia. The hazard
ratios for hyperuricemia, compared with HOMA-IR <=0.66, were 1.42 (95% confidence
interval 1.02-1.98) for HOMA-IR 0.67-0.98, 1.20 (0.86-1.68) for HOMA-IR 0.99-1.49
and 1.44 (1.04-1.98) for HOMA-IR >=1.50 after adjustment for baseline serum uric
acid, creatinine, hypercholesterolemia and hypertension status, age, alcohol
intake, and smoking and exercise habits. The hazard ratio associated with an
increase of one standard deviation in lnHOMA-IR (1.85 as one geometric standard
deviation of HOMA-IR) was 1.14 (1.03-1.28) (p for trend=0.02). CONCLUSIONS:
Increased HOMA-IR independently predicted the subsequent development of
hyperuricemia. Insulin resistance itself or compensatory hyperinsulinemia may
contribute to the development of hyperuricemia.
PMID- 25112920
TI - TRB3, up-regulated in kidneys of rats with type1 diabetes, mediates extracellular
matrix accumulation in vivo and in vitro.
AB - AIMS: Fibrosis is the final disorder of most chronic kidney disease including
diabetic nephropathy (DN), but the mechanisms are not fully understood. The
present study aims to determine whether TRB3 participates in fibrogenesis in DN.
METHODS: Type1 diabetes was induced in male Wistar rats via intraperitoneal
injection of streptozotocin (STZ). The expression of TRB3 and extracellular
matrix (ECM) protein collagen I and fibronectin was investigated in kidneys of
rats with diabetes and NRK-52E cells (a rat proximal tubular cell line)
stimulated with albumin-overload. Rats without diabetes and NRK-52E cells without
albumin stimulation served as control. Then gene silencing was used to study
whether TRB3 participated in accumulation of collagen I and fibronectin in vivo
and in vitro. RESULTS: TRB3 is up-regulated in renal tubules of kidneys of rats
with diabetes, especially proximal tubules. Albumin-overload can augments TRB3
expression and increase collagen I and fibronectin secretion in NRK-52E cells.
Importantly, silencing of TRB3 alleviates collagen I and fibronectin accumulation
in kidneys of rats with diabetes and NRK-52E cells induced by albumin-overload.
CONCLUSIONS: TRB3 mediates ECM accumulation in kidneys of rats with STZ-induced
type1 diabetes and proximal tubular cells induced by albumin-overload, suggesting
a potential target for treatment of DN.
PMID- 25112922
TI - Instant coffee consumption may be associated with higher risk of metabolic
syndrome in Korean adults.
AB - AIMS: Cumulative evidence suggests that coffee consumption may have beneficial
effects on metabolic diseases; however, few previous studies have considered the
types of coffee consumed and the additives used. We investigated the relationship
between coffee consumption and metabolic syndrome (MetSyn) and its components.
METHODS: We analyzed 17,953 Korean adults, aged 19-65 years, using cross
sectional data from the Korean National Health and Nutrition Examination Survey
(KNHANES, 2007-2011). Coffee consumption level, types of coffee consumed, and the
additives used were assessed based on a food frequency questionnaire and 24-h
recall. Demographic and lifestyle factors were assessed using self-administered
questionnaires. Data on metabolic biomarkers were obtained from a health
examination. Multivariable logistic regression was used to determine the odds
ratios of prevalent metabolic syndrome and its components according to frequency
and type of coffee consumption. RESULTS: We found that 76% of the subjects were
habitual coffee drinkers, most of whom consumed instant coffee mix containing
sugar and powder creamer. After multivariable adjustment, the odds ratios (95%
CI) comparing those who consumed coffee >=3 times/day with those who consumed
coffee <1 time/week were 1.37 (1.15-1.63) for obesity, 1.33 (1.11-1.59) for
abdominal obesity, 1.28 (1.09-1.51) for hypo-HDL cholesterolemia, and 1.37 (1.10
1.72) for metabolic syndrome. Instant-coffee drinkers were observed to have
elevated risks of these metabolic conditions. CONCLUSIONS: Consumption of coffee,
particularly instant coffee mix, may have harmful effects on MetSyn, perhaps
partly deriving from excessive intake of sugar and powder creamer.
PMID- 25112921
TI - Prevalence of diabetes and pre-diabetes among workers: Japan Epidemiology
Collaboration on Occupational Health Study.
AB - AIMS: Few studies have examined the prevalence of diabetes using glycated
hemoglobin (HbA1c), a newly recommended diagnostic test. We examined the
prevalence of diabetes and pre-diabetes using both HbA1c and fasting plasma
glucose (FPG) and their associations with risk factors for type 2 diabetes in a
large-scale Japanese working population. METHODS: Participants were 47,172 men
and 8280 women aged 20-69 years who received periodic health checkup in nine
companies which participated in the Japan Epidemiology Collaboration on
Occupational Health study. Participants were categorized into diabetes
(HbA1c>=6.5% (>=48mmol/mol), FPG>=126mg/dl (>=7.0mmol/L), or medication for
diabetes), pre-diabetes (HbA1c 6.0-6.4% (42-46mmol/mol) or FPG 110-125mg/dl (6.1
6.9mmol/L) among those without diabetes), and normal glucose regulation. RESULTS:
The prevalence of diabetes was 8.0% and 3.3% in men and women, respectively. Of
individuals with diabetes, approximately 80% were defined by HbA1c>=6.5%
(>=48mmol/mol) criterion. The prevalence of pre-diabetes was 14.1% in men and
9.2% in women. Prevalence of these glucose abnormalities increased with advancing
age, especially during mid-40s and 50s. Higher body mass index and waist
circumference, hypertension, dyslipidemia, and current smoking were each
associated with higher prevalence of diabetes in both men and women. CONCLUSIONS:
Using HbA1c and FPG criteria or current medication, one in 13 men and one in 30
women had diabetes in the present Japanese working population. Interventions
targeted for those in an early stage of impaired glucose metabolism would be
required to prevent diabetes.
PMID- 25112923
TI - Illness beliefs predict self-care behaviours in patients with diabetic foot
ulcers: a prospective study.
AB - AIMS: Patients' illness beliefs are known to be influential determinants of self
care behaviours in many chronic conditions. In a prospective observational study
we examined their role in predicting foot self-care behaviours in patients with
diabetic foot ulcers. METHODS: Patients (n=169) were recruited from outpatient
podiatry clinics. Clinical and demographic factors, illness beliefs and foot self
care behaviours were assessed as baseline (week 0). Foot self-care behaviours
were assessed again 6, 12 and 24 weeks later. Linear regressions examined the
contribution of beliefs at baseline to subsequent foot self-care behaviours,
controlling for past behaviour (i.e., foot self-care at baseline) and clinical
and demographic factors that may affect foot self-care (i.e., age and ulcer
size). RESULTS: Our models accounted for between 42 and 58% of the variance in
foot self-care behaviours. Even after controlling for past foot-care behaviours,
age and ulcer size; patients' beliefs regarding the symptoms associated with
ulceration, their understanding of ulceration and their perceived personal
control over ulceration emerged as independent determinants of foot self-care.
CONCLUSIONS: Patients' beliefs are important determinants of foot-care practices.
They may, therefore, also be influential in determining ulcer outcomes.
Interventions aimed at modifying illness beliefs may offer a means for promoting
self-care and improving ulcer outcomes.
PMID- 25112924
TI - The effect of six weeks endurance training on dynamic muscular control of the
knee following fatiguing exercise.
AB - The aim of the study was to examine whether six weeks of endurance training
minimizes the effects of fatigue on postural control during dynamic postural
perturbations. Eighteen healthy volunteers were assigned to either a 6-week
progressive endurance training program on a cycle ergometer or a control group.
At week 0 and 7, dynamic exercise was performed on an ergometer until exhaustion
and immediately after, the anterior-posterior centre of pressure (COP) sway was
analyzed during full body perturbations. Maximal voluntary contractions (MVC) of
the knee flexors and extensors, muscle fiber conduction velocity (MFCV) of the
vastus lateralis and medialis during sustained isometric knee extension
contractions, and power output were measured. Following the training protocol,
maximum knee extensor and flexor force and power output increased significantly
for the training group with no changes observed for the control group. Moreover,
the reduction of MFCV due to fatigue changed for the training group only (from
8.6% to 3.4%). At baseline, the fatiguing exercise induced an increase in the
centre of pressure sway during the perturbations in both groups (>10%). The
fatiguing protocol also impaired postural control in the control group when
measured at week 7. However, for the training group, sway was not altered after
the fatiguing exercise when assessed at week 7. In summary, six weeks of
endurance training delayed the onset of muscle fatigue and improved the ability
to control balance in response to postural perturbations in the presence of
muscle fatigue. Results implicate that endurance training should be included in
any injury prevention program.
PMID- 25112925
TI - Mental health lived experience academics in tertiary education: the views of
nurse academics.
AB - BACKGROUND: Australian national mental health strategy emphasises inclusion of
people diagnosed with mental illness in all areas of mental health care, policy
development and education of health professionals. However, the way this
inclusion has translated to Australian universities is relatively unexplored.
OBJECTIVES: Explore views of nurse academics regarding service user involvement
in nursing education programmes. DESIGN: Qualitative exploratory. SETTINGS:
Australian universities offering educational programmes in nursing at
postgraduate and undergraduate levels. PARTICIPANTS: Thirty four participants
from 27 Australian universities participated. METHODS: Data were collected using
semi-structured telephone interviews with academics involved in teaching and/or
coordinating undergraduate and/or postgraduate mental health nursing contents.
Data were analysed using content analysis based on four cognitive processes:
comprehending, synthesising, theorising and re-contextualising data. RESULTS:
Four major themes emerged: good idea? long way to go; conceptualising the service
user academic role; strengths of lived experience led student learning; and
barriers to implementation. CONCLUSIONS: Findings indicated strong support for
including mental health service users in teaching nursing students. However, at
most universities service user engagement was often an informal arrangement,
lacking clear guidelines and limited by financial barriers and the positioning of
mental health nursing within curricula.
PMID- 25112926
TI - Does a volume reduction of the parietal lobe contribute to freezing of gait in
Parkinson's disease?
AB - BACKGROUND: Freezing of gait (FOG) is as a brief, episodic absence or marked
reduction of forward progression of the feet despite the intention to walk.
Structural neuroimaging studies on FOG in PD using volumetric techniques yielded
variable and partially conflicting findings, probably reflecting the
heterogeneity and complexity of the phenomenon. The aim of this study was to
further explore the differences in local gray matter (GM) volume in patients with
PD with and without FOG by using Voxel-Based Morphometry (VBM). MATERIALS AND
METHODS: We enrolled 26 patients (7 women and 19 men) with a diagnosis of PD in
stable treatment with dopaminergic therapy. Thirteen patients classified as FOG+
were matched with thirteen non-freezer (FOG-) PD patients. All 26 participants
underwent a detailed neuropsychological assessment as well as a VBM analysis
derived from T1 weighted 3T MRI. RESULTS: The patient groups did not
significantly differ for age, disease duration, H&Y stage, UPDRS part-III or
educational attainment. No significant differences of cognitive profile emerged.
PD-FOG+ patients showed a pattern of relative GM atrophy in left posterior
parietal gyrus compared with PD-FOG-. DISCUSSION: Our results suggest that a
specific pattern of cortical volume reduction involving posterior parietal cortex
contributes to the occurrence of FOG in PD. These data agree with the growing
body of evidence considering the parietal posterior cortex as an associative area
involved in spatial control of motor behavior, par-taking in response selection
to sensory evaluation.
PMID- 25112927
TI - Wilate use in 47 children with von Willebrand disease: the North London
paediatric haemophilia network experience.
AB - Children with von Willebrand disease (VWD) in whom DDAVP is ineffective or
contraindicated require treatment with a coagulation factor concentrate
containing von Willebrand factor (VWF) and factor VIII (FVIII). The aim of this
study was to monitor the safety, efficacy and tolerability of Wilate((r)) (a
VWF:FVIII concentrate with a 1:1 ratio) used across the North London Paediatric
Haemophilia Network since May 2010. In total, 47 children (aged 0.0-17.0 years)
with type 1 (n = 28), type 2 (n = 7), type 3 (n = 10) and acquired VWS (n = 2)
have been treated for bleeds, surgery and/or prophylaxis using 260 000 IU
Wilate((r)). Analysis of dose and frequency of treatment show expected responses
to treatment with mean doses of 55, 50 and 50 IU kg(-1) for bleeds, surgery and
prophylaxis respectively. Most bleeds responded to a single treatment. Surgical
procedures were covered with clinician approved dosing schedules with 95% (39/41)
reported as having excellent or good efficacy. There was no accumulation of FVIII
or VWF and no thromboembolic events. This case series confirms the efficacy,
safety and tolerability of Wilate((r)) in neonates, children and adolescents when
used on-demand, prophylactically and in the surgical setting.
PMID- 25112928
TI - Propensity score-matched analysis of adjuvant chemotherapy for stage I non-small
cell lung cancer.
AB - OBJECTIVE: The aim of this study was to reevaluate the role of adjuvant
chemotherapy for patients with stage I non-small cell lung cancer (NSCLC).
METHODS: Data from 800 patients with completely resected pathologic stage I NSCLC
who received adjuvant chemotherapy (n=191) and those who did not (n=609) were
analyzed retrospectively and propensity score-matched pairs were determined.
RESULTS: Although recurrence-free survival (RFS) and overall survival (OS) were
not significantly different between patients who received adjuvant chemotherapy
and those who did not in the univariate analyses, multivariate Cox analyses
demonstrated that adjuvant chemotherapy was an independent prognostic factor for
RFS and OS (P=.008 and P=.009, respectively). In 159 propensity score-matched
pairs, including variables such as age, gender, smoking history, comorbidity,
postoperative complication, histology, size of the invasive component of the
tumor, and status of lymphatic, vascular, and pleural invasion, RFS and OS were
considerably better in patients who received adjuvant chemotherapy (5-year RFS
rate, 79.8%; 5-year OS rate, 89.3%) than in those who did not (5-year RFS rate,
60.2%; 5-year OS rate, 75.2%). Patients who received adjuvant chemotherapy showed
significantly better RFS than those who did not in the group with an invasive
component larger than 2 cm (5-year RFS rate, 74.4% vs 55.2%; P=.015) or in those
with positive lymphatic invasion (5-year RFS rate, 63.3% vs 44.8%; P=.05).
CONCLUSIONS: Adjuvant chemotherapy is effective for patients with stage I NSCLC,
particularly those with an invasive component larger than 2 cm or those with
lymphatic invasion.
PMID- 25112929
TI - The impact of arterial cannulation strategy on operative outcomes in aortic
surgery: evidence from a comprehensive meta-analysis of comparative studies on
4476 patients.
AB - OBJECTIVES: There is a growing perception that peripheral cannulation through the
femoral artery, by reversing the flow in the thoracoabdominal aorta, may increase
the risk of retrograde brain embolization in aortic surgery. Central cannulation
sites, including the right axillary artery, have been reported to improve
operative outcomes by allowing antegrade blood flow. However, peripheral
cannulation still remains largely used because a consensus for the routine use of
central cannulation approaches has not been reached. METHODS: A meta-analysis of
comparative studies reporting operative outcomes using central cannulation versus
peripheral cannulation was performed. Pooled weighted incidence rates for end
points of interest were obtained using an inverse variance model. RESULTS: A
total of 4476 patients were included in the final analysis. Central cannulation
was used in 2797 patients, and peripheral cannulation was used in 1679 patients.
Central cannulation showed a protective effect on in-hospital mortality (risk
ratio, 0.59; 95% confidence interval, 0.48-0.7; P < .001) and permanent
neurologic deficit (risk ratio, 0.71; 95% confidence interval, 0.55-0.90; P =
.005) when compared with peripheral cannulation. A trend toward an increased
benefit in terms of reduced in-hospital mortality was observed when only the
right axillary artery was used as the central cannulation approach (risk ratio,
0.35; 95% confidence interval, 0.22-0.55; P < .001; I(2) = 0%). CONCLUSIONS:
Central cannulation was superior to peripheral cannulation in reducing in
hospital mortality and the incidence of permanent neurologic deficit. This
superiority was particularly evident when the axillary artery was used for
central cannulation.
PMID- 25112930
TI - Long-term results of aggressive hemiarch replacement in 534 patients with type A
aortic dissection.
AB - OBJECTIVE: To present the outcomes of routinely performed hemiarch replacement in
patients with acute type A aortic dissection. METHODS: From 1993 to 2013, among
629 patients with acute type A dissection, 534 patients (85%) underwent hemiarch,
63 patients (10%) underwent hemiarch and antegrade thoracic stent grafting, 26
patients (4%) underwent total arch, and 6 patients (1%) underwent isolated
ascending replacement. Patients with hemiarch replacement comprised the study
population. Median follow-up was 4.1 years (first quartile, 1.9; third quartile,
7.8) (2462 patient years). RESULTS: In-hospital mortality was 12% (66 out of 534
patients). Survival was 80% +/- 2%, 68% +/- 3%, and 51% +/- 3%, and 84% +/- 3%,
65% +/- 4%, and 41% +/- 6% in DeBakey type I and II patients at 1, 5, and 10
years, respectively (log rank P = .375). Freedom from distal aortic
reintervention was 97% +/- 1%, 90% +/- 2%, and 85% +/- 3% and 99% +/- 1%, 97% +/-
2%, and 90% +/- 5% in DeBakey type I and II patients at 1, 5, and 10 years,
respectively (log rank P = .046). Seven patients (1.3%) required reintervention
for aortic arch aneurysm and 25 patients (5%) required reintervention for
descending aortopathy. The success rate for distal reintervention performed
electively or urgently was 92% (24 out of 26 patients). Marfan syndrome (odds
ratio, 3.43; P = .046) and DeBakey type I dissection (odds ratio, 2.49; P = .048)
were independent predictors of distal aortic reintervention. CONCLUSIONS:
Aggressive hemiarch replacement in acute type A dissection can be performed with
low mortality and low aortic arch reoperation rate. Resection of all dissected
aortic wall tissue decreases, but does not eliminate, the risk of later adverse
aortic events.
PMID- 25112932
TI - Synergistic protein secretion by mesenchymal stromal cells seeded in 3D scaffolds
and circulating leukocytes in physiological flow.
AB - Mesenchymal stromal cells (MSC) play an important role in natural wound healing
via paracrine and juxtacrine signaling to immune cells. The aim of this study was
to identify the signaling factors secreted by preseeded cells in a biomaterial
and their interaction with circulating leukocytes, in the presence of
physiological biomechanical stimuli exerted by the hemodynamic environment (i.e.
strain and shear flow). Electrospun poly(epsilon-caprolactone)-based scaffolds
were seeded with human peripheral blood mononuclear cells (PBMC) or MSC. Protein
secretion was analyzed under static conditions and cyclic strain. Subsequently,
the cross-talk between preseeded cells and circulating leukocytes was addressed
by exposing the scaffolds to a suspension of PBMC in static transwells and in
pulsatile flow. Our results revealed that PBMC exposed to the scaffold
consistently secreted a cocktail of immunomodulatory proteins under all
conditions tested. Preseeded MSC, on the other hand, secreted the trophic factors
MCP-1, VEGF and bFGF. Furthermore, we observed a synergistic upregulation of
CXCL12 gene expression and a synergistic increase in bFGF protein production by
preseeded MSC exposed to PBMC in pulsatile flow. These findings identify CXCL12
and bFGF as valuable targets for the development of safe and effective acellular
instructive grafts for application in in situ cardiovascular regenerative
therapies.
PMID- 25112931
TI - Phylogenetic analysis and evolutionary origins of DNA polymerase X-family
members.
AB - Mammalian DNA polymerase (pol) beta is the founding member of a large group of
DNA polymerases now termed the X-family. DNA polymerase beta has been
kinetically, structurally, and biologically well characterized and can serve as a
phylogenetic reference. Accordingly, we have performed a phylogenetic analysis to
understand the relationship between pol beta and other members of the X-family of
DNA polymerases. The bacterial X-family DNA polymerases, Saccharomyces cerevisiae
pol IV, and four mammalian X-family polymerases appear to be directly related.
These enzymes originated from an ancient common ancestor characterized in two
Bacillus species. Understanding distinct functions for each of the X-family
polymerases, evolving from a common bacterial ancestor is of significant interest
in light of the specialized roles of these enzymes in DNA metabolism.
PMID- 25112933
TI - In vivo assessment of guided neural stem cell differentiation in growth factor
immobilized chitosan-based hydrogel scaffolds.
AB - In this study, we demonstrate that a unique growth factor-biomaterial system can
offer spatial control of growth factors with sustained signaling to guide the
specific lineage commitment of neural stem/progenitor cells (NSPCs) in vivo.
First, recombinant fusion proteins incorporating an N-terminal biotin tag and
interferon-gamma (IFN-gamma), platelet derived growth factor-AA (PDGF-AA), or
bone morphogenic protein-2 (BMP-2) were immobilized to a methacrylamide chitosan
(MAC) based biopolymer via a streptavidin linker to specify NSPC differentiation
into neurons, oligodendrocytes, or astrocytes, respectively. MAC was mixed with
growth factors (immobilized or adsorbed), acrylated laminin, NSPCs, and
crosslinked within chitosan conduits. This system mimics regenerative aspects of
the central nervous system ECM, which is largely composed of a crosslinked
polysaccharide matrix with cell-adhesive regions, and adds the new functionality
of protein sequestration. We demonstrated that these growth factors are
maintained at functionally significant levels for 28 d in vitro. In the main
study, immobilized treatments were compared to absorbed and control treatments
after 28 d in vivo (rat subcutaneous). Masson's Trichrome staining revealed that
small collagen capsules formed around the chitosan conduits with an average
acceptable thickness of 153.07 +/- 6.02 MUm for all groups. ED-1 staining showed
mild macrophage clustering around the outside of chitosan conduits in all
treatments with no macrophage invasion into hydrogel portions. Importantly, NSPC
differentiation staining demonstrated that immobilized growth factors induced the
majority of cells to differentiate into the desired cell types as compared with
adsorbed growth factor treatments and controls by day 28. Interestingly,
immobilized IFN-gamma resulted in neural rosette-like arrangements and even
structures resembling neural tubes, suggesting this treatment can lead to guided
dedifferentiation and subsequent neurulation.
PMID- 25112934
TI - X-ray CT guided fault-free photothermal ablation of metastatic lymph nodes with
ultrafine HER-2 targeting W18O49 nanoparticles.
AB - Designing high accuracy in the diagnosing and fault-freely eliminating lymphatic
metastasis of breast malignancy, to avoid the invasiveness and complications
caused by traditional assays, is of great therapeutic importance. To this end,
theranostic W18O49 nanoparticles targeting to human epidermal growth receptor 2
(HER-2) over-expressed breast malignancy were synthesized via polyol method. By
taking advantage of their high X-ray attenuating and photothermotherapy potency,
lymph nodes in the mice bearing HER-2 positive metastasis could be clearly
distinguished under CT guidance and selectively eliminated by laser ablation. The
therapeutic efficacy was further confirmed by the significantly extended survival
period. These finding evidenced the potential of these nanoparticles for imaging
guided photothermal ablation of HER-2 positive breast malignancy.
PMID- 25112936
TI - Tissue engineering of electrically responsive tissues using polyaniline based
polymers: a review.
AB - Conducting polymers have found numerous applications as biomaterial components
serving to effectively deliver electrical signals from an external source to the
seeded cells. Several cell types including cardiomyocytes, neurons, and
osteoblasts respond to electrical signals by improving their functional outcomes.
Although a wide variety of conducting polymers are available, polyaniline (PANI)
has emerged as a popular choice due to its attractive properties such as ease of
synthesis, tunable conductivity, environmental stability, and biocompatibility.
PANI in its pure form has exhibited biocompatibility both in vitro and in vivo,
and has been combined with a host of biodegradable polymers to form composites
having a range of mechanical, electrical, and surface properties. Moreover,
recent studies in literature report on the functionalization of polyaniline
oligomers with end segments that make it biodegradable and improve its
biocompatibility, two properties which make these materials highly desirable for
applications in tissue engineering. This review will discuss the features and
properties of PANI based composites that make them effective biomaterials, and it
provides a comprehensive summary of studies where the use of PANI as a
biomaterial component has enhanced cellular function and behavior. We also
discuss recent studies utilizing functionalized PANI oligomers, and conclude that
electroactive PANI and its derivatives show great promise in eliciting favorable
responses from various cell lines that respond to electrical stimuli, and are
therefore effective biomaterials for the engineering of electrically responsive
biological tissues and organs.
PMID- 25112935
TI - Multi-layered nanoparticles for combination gene and drug delivery to tumors.
AB - Drug resistance and toxicity are major obstacles in cancer chemotherapy.
Combination therapies can overcome resistance, and synergies can minimize dosing.
Polymer nanocarriers are interesting vehicles for cancer therapeutics for their
delivery and tumor targeting abilities. We synthesized a multi-layered polymer
nanoparticle (MLNP), comprising of poly(lactic-co-glycolic acid) with surface
polyethyleneimine and functional peptides, for targeted drug and gene delivery.
We confirmed the particle's ability to inhibit tumor growth through synergistic
action of the drug and gene product. MLNPs achieved transfection levels similar
to lipofectamine, while maintaining minimal cytotoxicity. The particles delivered
camptothecin (CPT), and plasmid encoding TNF related apoptosis inducing ligand
(pTRAIL) (CT MLNPs), and synergistically inhibited growth of multiple cancer
cells in vitro. The synergy of co-delivering CPT and pTRAIL via CT MLNPs was
confirmed using the Chou-Talalay method: the combination index (CI) values at 50%
inhibition ranged between 0.31 and 0.53 for all cell lines. Further, co-delivery
with MLNPs resulted in a 3.1-15 fold reduction in CPT and 4.7-8.0 fold reduction
in pTRAIL dosing. CT MLNPs obtained significant HCT116 growth inhibition in vivo
compared to monotherapy. These results support our hypothesis that MLNPs can
deliver both small molecules and genetic agents towards synergistically
inhibiting tumor growth.
PMID- 25112937
TI - In vitro and in vivo anti-biofilm effects of silver nanoparticles immobilized on
titanium.
AB - Prevention of periprosthetic infection (PPI) by inhibiting biofilm formation on
prostheses is crucial to orthopedic surgery. In this work, silver nanoparticles
(Ag NPs) are fabricated in situ and immobilized on titanium by silver plasma
immersion ion implantation (PIII). The anti-biofilm activity rendered by the
immobilized Ag NPs is assessed using Staphylococcus epidermidis, a biofilm
producing strain, in vitro and in vivo. The immobilized Ag NPs show no apparent
cytotoxicity but reduce biofilm formation in vitro by inhibiting bacteria
adhesion and icaAD transcription. The immobilized Ag NPs offer a good defense
against multiple cycles of bacteria attack in vitro, and the mechanism is
independent of silver release. Radiographic assessment, microbiological cultures,
and histopathological results demonstrate the ability of the functionalized
surface against bacterial infection to reduce the risk of implant-associated PPI.
PMID- 25112938
TI - Synergistic effect of amino acids modified on dendrimer surface in gene delivery.
AB - Design of an efficient gene vector based on dendrimer remains a great challenge
due to the presence of multiple barriers in gene delivery. Single
functionalization on dendrimer cannot overcome all the barriers. In this study,
we synthesized a list of single-, dual- and triple-functionalized dendrimers with
arginine, phenylalanine and histidine for gene delivery using a one-pot approach.
The three amino acids play different roles in gene delivery: arginine is
essential in formation of stable complexes, phenylalanine improves cellular
uptake efficacy, and histidine increases pH-buffering capacity and minimizes
cytotoxicity of the cationic dendrimer. A combination of these amino acids on
dendrimer generates a synergistic effect in gene delivery. The dual- and triple
functionalized dendrimers show minimal cytotoxicity on the transfected NIH 3T3
cells. Using this combination strategy, we can obtain triple-functionalized
dendrimers with comparable transfection efficacy to several commercial
transfection reagents. Such a combination strategy should be applicable to the
design of efficient and biocompatible gene vectors for gene delivery.
PMID- 25112941
TI - Relationship between cervical sagittal alignment and quality of life in
ankylosing spondylitis.
AB - PURPOSE: Little information is available on the relationship between cervical
sagittal alignment and health-related quality of life (HRQOL) in ankylosing
spondylitis (AS) patients. The aim of this study was to identify relationships
between cervical sagittal alignment and HRQOL in AS. METHODS: The study and
control groups comprised 102 AS patients (15 women and 87 men) and age- and sex
matched 50 controls, respectively. All underwent anteroposterior and lateral
radiographs and completed clinical questionnaires. The radiographic parameters
examined were C2-C7 lordosis, C2-C7 sagittal vertical axis (SVA), T1 slope and T1
slope minus C2-C7 lordosis (TS-CL). A visual analogue scale (VAS 0-10) score for
neck pain, the neck disability index (NDI), neck pain and disability (NPAD) scale
and bath ankylosing spondylitis disease activity index (BASDAI) were administered
to evaluate QOL. Statistical analysis was performed to determine the
significances of differences between the study and control groups. In addition,
correlations between radiological parameters and clinical questionnaires were
sought. RESULTS: AS patients and controls were found to be different
significantly in terms of C2-C7 SVA, T1 slope, and TS-CL. However, no significant
intergroup difference was observed for C2-C7 lordosis (P > 0.05). Correlation
analysis revealed significant relationships between radiographic parameters and
QOL. Multiple regression analysis was performed to identify predictors of QOL,
and the results obtained revealed that C2-C7 SVA significantly predicted VAS,
NDI, and NPAD scores and that age predicted NPAD score. CONCLUSIONS: Cervical
sagittal parameters were found to be significantly different in AS patients and
normal controls. Correlation analysis revealed significant relationships between
radiographic parameters and QOL. In particular, C2-C7 SVA was found to be a
significant predictor of QOL in AS patient.
PMID- 25112942
TI - Atypical C2 fracture treated by posterior atlantoaxial fusion according to
Goel/Harms.
PMID- 25112943
TI - Functional connectivity in rat brain at 200 MUm resolution.
AB - The somatosensory functional magnetic resonance imaging (fMRI) response to
electrical stimulation of the middle phalange of the second digit of four rats at
a spatial resolution of 200 MUm cubic at 9.4 T is reported. At high threshold
(p<0.002), activated voxels encompass a penetrating vein that passes across the
gray matter. These voxels lie mostly in three contiguous slices perpendicular to
the pial surface. This activation is assigned to the representation in the
forepaw barrel subfield (FBS) of a single cortical column of this phalange. In
addition, the activation of the indusium griseum (IG) is visualized robustly.
Voxels revealed by fMRI were used to observe functional connectivity to other
voxels of the sensorimotor cortex using fcMRI. Results of this experiment were
analyzed as a function of decreasing threshold, which exhibited spreading
connectivity that revealed S2, M1/M2, and contralateral S1. Noting that every
cubic millimeter of tissue contains 125 voxels, connectivity patterns are
complex. It is hypothesized that they reflect connections within gray matter by
association fibers. S2 and IG revealed connectivities with many voxels across the
sensorimotor cortex. These regions also showed subregional variation of
connectivity. A 1-cm-diameter surface coil with a local low-noise RF amplifier
was used in these studies. The usual region of sensitivity (ROS) of such a coil
is 1 cm diameter by 0.5 cm depth. Significant connectivity was observed between
time courses of voxels that were within the ROS and voxels that were outside,
which extends the volume of tissue that can be observed by the methods of this
article.
PMID- 25112944
TI - Client and key worker ratings of need in first-episode psychosis early
intervention programmes.
AB - AIM: The aim of this study was to fill a gap in the literature by examining
agreement on need as rated by clients and their key workers from first-episode
psychosis early intervention programmes. Compared with adult populations and more
chronic courses of illness, these clients may have unique needs given the onset
of their illness in adolescence or early adulthood. METHODS: Needs agreement
between clients and key workers was assessed using the Camberwell Assessment of
Need in a sample of 188 client-key worker pairs recruited from six early
intervention programmes in Ontario, Canada. Ratings were assessed with percentage
agreement and prevalence-adjusted Cohen's kappa. RESULTS: At the aggregate level,
both clients and key workers rated a mean of 2.6 unmet needs. Compared with other
diagnoses, key workers rated significantly more unmet need in clients with
primary psychotic disorders. Agreement between individual client and key worker
ratings was highest (adjusted kappa > 0.85) in the domains of telephone, risk to
others, child care and accommodation. Lowest agreement (adjusted kappa < 0.4) was
found in the domains of psychological distress, sexual expression, company,
daytime activities and intimate relationships. CONCLUSIONS: While congruence is
present in concrete domains, there is substantial variability in how clients and
their key workers perceive need in more personal areas. The initial focus of care
may necessarily be on needs such as shelter, food and treatment; however,
subsequent care should incorporate a shared assessment of need to support strong
relationships with providers and ongoing engagement in treatment.
PMID- 25112945
TI - Vitamin B deficiencies in a critically ill autistic child with a restricted diet.
AB - An 11-year-old male with autism became less responsive and was hospitalized with
hepatomegaly and liver dysfunction, as well as severe lactic acidosis. His diet
for several years was self-limited exclusively to a single "fast food"-a
particular type of fried chicken-and was deficient in multiple micronutrients,
including the B vitamins thiamine and pyridoxine. Lactic acidosis improved
rapidly with thiamine; 2 weeks later, status epilepticus-with low serum
pyridoxine-resolved rapidly with pyridoxine. Dietary B vitamin deficiencies
complicated the care of this critically ill autistic child and should be
considered in this setting.
PMID- 25112946
TI - The personality of emergency nurses: is it unique?
AB - BACKGROUND: With ever increasing demands on emergency services it is necessary to
consider how to enhance the recruitment and retention of emergency nurses in
public hospitals. Personality is known to influence occupational choice, yet
there is a lack of research exploring how personality may influence the workforce
decisions of emergency nurses. METHODS: A standardised personality test
instrument, the NEOTM-PI-3, was used in a survey design inclusive of demographic
questions to measure personality characteristics. Data were collected from 72
emergency nurses working at an Australian Emergency Department between July and
October 2012. The personality scores of emergency nurses were compared against
general population norms in each of five personality domains and their 30
associated facets. RESULTS: Participants scored higher than population norms in
the domains of Extraversion (p < .001), Openness to experience (p < .001) and
Agreeableness (p = .001), and in twelve facets, including excitement-seeking (p <
.001) and competence (p = .003). CONCLUSION: The personality profile of this
sample of emergency nurses is different to the population norm. Assessment of
personality and knowledge of its influence on specialty selection may assist in
improving retention and recruitment in emergency nursing.
PMID- 25112947
TI - The emergency department prediction of disposition (EPOD) study.
AB - BACKGROUND: Emergency departments (ED) continue to evolve models of care and
streaming as interventions to tackle the effects of access block and
overcrowding. Tertiary ED may be able to design patient-flow based on predicted
dispositions in the department. Segregating discharge-stream patients may help
develop patient-flows within the department, which is less affected by
availability of beds in a hospital. We aim to determine if triage nurses and ED
doctors can predict disposition outcomes early in the patient journey and thus
lead to successful streaming of patients in the ED. METHODS: During this study,
triage nurses and ED doctors anonymously predicted disposition outcomes for
patients presenting to triage after their brief assessments. Patient disposition
at the 24-h post ED presentation was considered as the actual outcome and
compared against predicted outcomes. RESULTS: Triage nurses were able to predict
actual discharges of 445 patients out of 490 patients with a positive predictive
value (PPV) of 90.8% (95% CI 87.8-93.2%). ED registrars were able to predict
actual discharges of 85 patients out of 93 patients with PPV of 91.4% (95% CI
83.3-95.9%). ED consultants were able to predict actual discharges of 111
patients out of 118 patients with PPV 94.1% (95% CI 87.7-97.4%). PPVs for
admission among ED consultants, ED registrars and Triage nurses were 59.7%, 54.4%
and 48.5% respectively. CONCLUSIONS: Triage nurses, ED consultants and ED
registrars are able to predict a patient's discharge disposition at triage with
high levels of confidence. Triage nurses, ED consultants, and ED registrars can
predict patients who are likely to be admitted with equal ability. This data may
be used to develop specific admission and discharge streams based on early
decision-making in EDs by triage nurses, ED registrars or ED consultants.
PMID- 25112950
TI - [Gender-specific aspects of coronary heart disease].
AB - The total number of deaths from cardiovascular diseases (CVD) is greater for
women than for men, although the mean age at manifestation of CVD is about 10
years older. However, the annual number of cases treated for CVD in acute
hospital settings in men exceeds that of women by 50 %. Remarkable gender
differences exist in terms of morphological and physiological conditions (e.g.
mean coronary vessel diameter; ability to adapt to protective exercise-induced
myocardial hypertrophy), as well as of the frequency and clinical significance of
somatic risk factors (e.g. smoking). Female body weight increases after menopause
and the body shape assumes a more android fat distribution. Women report higher
levels of unspecific and affective symptoms. They suffer more from anxiety and
depression than men; however, the secondary impact on CVD onset may be less
pronounced. The post-acute CVD course is more complicated in women, mainly
because they are older and suffer more from multi-morbidity. Whilst male CVD
patients aim for a rapid recovery, physical fitness and an increased life
expectancy, female patients seek relief from everyday challenges, the maintenance
of their independence and emotional support.
PMID- 25112951
TI - [Health and gender].
PMID- 25112948
TI - Association of lifestyle habits and academic achievement in Norwegian
adolescents: a cross-sectional study.
AB - BACKGROUND: While healthy lifestyle habits are generally assumed to be important
for high academic achievement, there has been little research on this topic among
adolescents. The aim of this study was therefore to examine the associations
between several lifestyle habits and academic achievement in adolescent girls and
boys. METHODS: The study included 2,432 Norwegian adolescents, 15-17 years old. A
self-report questionnaire was used to assess dietary-, physical activity-,
smoking- and snuffing habits and academic achievement. Logistic regression models
were adjusted for body mass index (BMI) and parental education. RESULTS: In both
girls and boys, high academic achievement was associated with a regular
consumption of breakfast (AOR: 3.30 (2.45-4.45) and AOR: 1.76 (1.32-2.34),
respectively) and lunch (AOR: 1.44 (1.08-1.93) and AOR: 1.43 (1.09-1.89),
respectively), and in boys, with a regular consumption of dinner (AOR: 1.44 (1.16
1.79)) and a regular meal pattern in general (AOR: 1.50 (1.10 - 2.03)). In both
girls and boys, high academic achievement was associated with a high intake of
fruit and berries (AOR: 2.09 (1.51-2.88) and AOR: 1.47 (1.04-2.07),
respectively), and in girls, with a high intake of vegetables (AOR: 1.82 (1.30
2.53)). In both girls and boys, high academic achievement was associated with a
high leisure time physical activity level (AOR: 1.51 (1.10-2.08) and AOR: 1.39
(1.05-1.85), respectively) and use of active commuting (AOR: 1.51 (1.10-2.08) and
AOR: 1.72 (1.26-2.35), respectively). In both girls and boys, high academic
achievement was associated with a low intake of lemonade (AOR: 0.42 (0.27-0.64)
and AOR: 0.67 (0.48-0.94), respectively), and in girls, with a low intake of
sugar-sweetened soft drinks (AOR: 0.47 (0.35- 0.64)) and salty snacks (AOR: 0.63
(0.47-0.85)). Lastly, high academic achievement was inversely associated with
smoking and snuffing in both girls (AOR: 0.18 (0.12-0.25) and AOR: 0.25 (0.17
0.37), respectively) and boys (AOR: 0.37 (0.25-0.54) and AOR: 0.51 (0.36-0.72),
respectively). CONCLUSIONS: A regular meal pattern, an intake of healthy food
items and being physically active were all associated with increased odds of high
academic achievement, whereas the intake of unhealthy food and beverages, smoking
cigarettes and snuffing were associated with decreased odds of high academic
achievement in Norwegian adolescents.
PMID- 25112952
TI - [The EDQM Biological Standardisation Programme for the development of methods and
reference preparations].
AB - The Biological Standardisation Programme (BSP) of the European Directorate for
the Quality of Medicines & HealthCare (EDQM) was founded in 1992 with the
objective to provide the necessary tools for the quality controls prescribed by
the European Pharmacopoeia (Ph. Eur.). The BSP accomplishes this task by
establishing reference standards and materials, as well as standardised control
methods. A key aspect of BSP's work on development of methods is the validation
of methods which can replace Ph. Eur. tests involving animals. The current area
of work includes vaccines (for human and animal use), medicines produced from
human plasma, hormones, cytokines, allergens, as well as reference materials and
methods for determination of impurities and contaminations. BSP closely
collaborates with the World Health Organization (WHO) and national authorities;
many reference standards are established in joint projects with WHO. Participants
of studies for establishing of reference materials and methods are mainly
national control laboratories and manufacturers. BSP has to date run 131
projects, whereby 121 reference materials were established. Method development
was the objective of 38 projects, with 21 thereof aiming at replacement of animal
tests. BSP is funded by the EDQM (Council of Europe) and by the European
Commission. With its activities BSP makes a significant contribution to quality,
safety and efficacy of biological medicinal products in Europe and beyond, and
serves thereby health and well-being of human beings and animals.
PMID- 25112953
TI - 2'-Deoxyuridine conjugated with a reactive monobenzocyclooctyne as a DNA building
block for copper-free click-type postsynthetic modification of DNA.
AB - The carboxymethylmonobenzocyclooctyne group attached to the 5-position of a 2'
deoxyuridine in DNA allows rapid and efficient copper-free postsynthetic
modification as demonstrated with a far-red emitting fluorescent azide probe.
Upon labeling strong fluorescence intensity enhancement is observed.
PMID- 25112954
TI - Prevalence of macrolide, lincosamide, and streptogramin resistance among
staphylococci in a tertiary care hospital in Athens, Greece.
AB - The aims of the present study were to evaluate erythromycin, clindamycin, and
streptogramin resistance rates, as well as the phenotypic and genotypic
characteristics of erythromycin-resistant staphylococci in a Greek University
Hospital. Macrolide, lincosamide, and streptogramin B-type resistance was
investigated by double disk diffusion and the D-zone testing, while Minimal
inhibitory concentration determination was performed among 656 erythromycin
resistant staphylococcal clinical consecutive isolates, too. The presence of the
major genetic determinants ermA, ermB, ermC, and msrA were detected by polymerase
chain reaction (PCR). The overall erythromycin resistance rate was 49.70%. One
hundred and forty-six of the 322 Staphylococcus aureus were methicillin-resistant
S. aureus (MRSA) (45.34%), whereas 176 were methicillin-susceptible S. aureus
(54.66%). The macrolides, lincosamides, and streptogramin B-type antibiotics
(MLSB)-constitutive phenotype was detected in 126 S. aureus strains (88.7%),
whereas the inducible MLSB resistance phenotype was demonstrated in 16 S. aureus
(11.3%). The MS phenotype was not detected. ErmC was the most frequently
encountered gene responsible for macrolide resistance among S. aureus and
coagulase negative staphylococci in this hospital. Pulsed-field gel
electrophoresis (PFGE) analysis of SmaI DNA fragments revealed the presence of a
single predominant clone among erythromycin-resistant S. aureus. The predominance
of constitutive erythromycin resistance is a serious problem and limits the use
of clindamycin for severe staphylococcal infections not only in this university
hospital, but in many countries worldwide.
PMID- 25112955
TI - mecA-positive methicillin-sensitive Staphylococcus aureus clinical isolates in
Zenica-Doboj Canton, Bosnia and Herzegovina.
AB - Forty-four mecA-positive and eight mecA-negative Staphylococcus aureus isolates
confirmed by PCR were further tested by disc-diffusion (DD) oxacillin and
cefoxitin, oxacillin Epsilon (E)-test, and oxacillin and cefoxitin minimal
inhibitory concentration (MIC) Strip methicillin-resistant phenotype in S. aureus
(MRSA) tests. Among 44 mecA-positive S. aureus isolates, two (4.5%) were detected
as MRSA by DD-oxacillin, 17 (38.6%) by DD-cefoxitin test, and seven (15.9%) by
the E-test. In the cefoxitin MIC Strip MRSA test, 19 (43.2%) isolates were
resistant. In the oxacillin MIC Strip MRSA test, 18 (40.9%) isolates were
resistant and 26 (59.1%) were sensitive, i.e. oxacillin-sensitive MRSA (OS-MRSA)
(MIC range 0.25-<=0.25 mg/l). Fifteen out of 26 OS-MRSA (57.7%) belonged to spa
CC 355/595, 78% of which belonged to the largest PFGE clone. Some discrepancies
between the phenotypic methods for MRSA identification obtained in this study
were caused by large proportion of OS-MRSA. Misidentification of OS-MRSA as MSSA
might result in an appearance of highly resistant MRSA in patients treated with
beta-lactam antibiotics.
PMID- 25112956
TI - Exome sequencing identifies frequent mutation of MLL2 in non-small cell lung
carcinoma from Chinese patients.
AB - Lung cancer is the most common cause of cancer mortality worldwide, with an
estimated 1.4 million deaths each year. Here we report whole-exome sequencing of
nine tumor/normal tissue pairs from Chinese patients with non-small cell lung
carcinoma (NSCLC). This allows us to identify a number of significantly mutated
genes in NSCLC, which were highly enriched in DNA damage repair, NF-kappaB
pathway, JAK/STAT signaling and chromatin modification. Notably, we identify a
histone-lysine methyltransferase gene, namely, MLL2, as one of the most
significantly mutated genes in our screen. In a following validation study, we
identify deleterious mutations of MLL2 in 12 out of 105 (11.4%) NSCLC patients.
Additionally, reduced or lost expression of MLL2 was commonly observed in tumor
tissues as compared with paired adjacent non-tumor tissues regardless of mutation
status. Together, our study defines the landscape of somatic mutations in Chinese
NSCLC and supports the role of MLL2 mutation in the pathogenesis of the disease.
PMID- 25112957
TI - Emergent severe acute respiratory distress syndrome caused by adenovirus type 55
in immunocompetent adults in 2013: a prospective observational study.
AB - INTRODUCTION: Since 2008, severe cases of emerging human adenovirus type 55 (HAdV
55) in immunocompetent adults have been reported sporadically in China. The
clinical features and outcomes of the most critically ill patients with severe
acute respiratory distress syndrome (ARDS) caused by HAdV-55 requiring invasive
mechanical ventilation (IMV) and/or extracorporeal membrane oxygenation (ECMO)
are lacking. METHODS: We conducted a prospective, single-center observational
study of pneumonia with ARDS in immunocompetent adults admitted to our
respiratory ICU. We prospectively collected and analyzed clinical, laboratory,
radiological characteristics, sequential tests of viral load in respiratory tract
and blood, treatments and outcomes. RESULTS: The results for a total of five
consecutive patients with severe ARDS with confirmed HAdV-55 infection were
included. All five patients were immunocompetent young men with a median age of
32 years. The mean time from onset to dyspnea was 5 days. Arterial blood gas
analysis at ICU admission revealed profound hypoxia. Mean partial oxygen
pressure/fraction of inspired oxygen was 58.1. Mean durations from onset to a
single-lobe consolidation shown on chest X-rays (CXRs) and, from the first
positive CXR to bilateral multilobar lung infiltrates, were 2 days and 4.8 days,
respectively. The viral load was higher than 1 * 108 copies in three patients and
was 1 * 104 in one patient. It was negative in the only patient who survived. The
mean duration for noninvasive positive pressure ventilation (NPPV) failure and
IMV failure were 30.8 hours and 6.2 days, respectively. Four patients received
venovenous ECMO. Four (80%) of the five patients died despite receiving
appropriate respiratory support. CONCLUSIONS: HAdV-55 may cause severe ARDS in
immunocompetent young men. Persistent high fever, dyspnea and rapid progression
to respiratory failure within 2 weeks, together with bilateral consolidations and
infiltrates, are the most frequent clinical manifestations of HAdV-55-induced
severe ARDS. Viral load monitoring may help predict disease severity and outcome.
The NPPV and IMV failure rates were very high, but ECMO may still be the
respiratory support therapy of choice. TRIAL REGISTRATION: Clinicaltrials.gov
NCT01585922. Registered 20 April 2012.
PMID- 25112958
TI - Stereospecific hydrolysis of a phosphoramidate used as an OPIDP model by human
sera with PON1 192 alloforms.
AB - O-hexyl 2,5-dichlorophenyl phosphoramidate (HDCP) is a racemic organophosphate
compound (OP) that induces delayed neuropathy in vivo. The O-hexyl 2,5
dichlorophenyl phosphoramidate R (R-HDCP) isomer inhibits and ages neuropathic
target esterase (NTE) in hen brain. Moreover, human serum paraoxonase-1 (PON1) is
a Ca(2+)-dependent enzyme capable of hydrolyzing OPs. The enzymatic activity of
PON1 against OPs depends on the genetic polymorphisms present at position 192
(glutamine or arginine). The catalytic efficiency of PON1 is an important factor
that determines neurotoxic susceptibility to some OPs. In the present study, we
characterized the stereospecific hydrolysis of HDCP by alloforms PON1 Q192R human
serum by chiral chromatography. Forty-seven human samples were characterized for
the PON1 192 polymorphism. The hydrolysis data demonstrate that the three
alloforms of PON1 show an exclusive and significant stereospecific Ca(2+)
dependent hydrolysis of O-hexyl 2,5-dichlorophenyl phosphoramidate S isomer (S
HDCP) at 19-127 uM at the concentrations that remain in all the samples. This
stereoselective Ca(2+)-dependent hydrolysis of S-HDCP is inhibited by EDTA and is
independent of the PON1 Q192R alloform. The present research reinforces the
hypothesis that R-HDCP (an isomer that inhibits and causes NTE aging) is the
enantiomer that induces delayed neuropathy by this chiral phosphoramidate due to
the low hydrolysis level of the R-HDCP observed in this study.
PMID- 25112959
TI - Re: Waalkes et al.: Lung tumors in mice induced by "whole-life" inorganic arsenic
exposure at human-relevant doses, Arch Toxicol, 2014.
PMID- 25112960
TI - Evaluation of apically extruded debris associated with several Ni-Ti systems.
AB - AIM: To evaluate the apical extrusion of debris associated with several root
canal preparation systems in vitro. METHODOLOGY: Forty-five extracted human
mandibular premolars with single canals and similar lengths were used. The root
canals were instrumented using ProTaper Next (Dentsply Maillefer, Ballaigues,
Switzerland), Twisted File (SybronEndo, Orange, CA, USA) or WaveOne (Dentsply
Maillefer, Ballaigues, Switzerland). Debris extruded apically during
instrumentation was collected into pre-weighed Eppendorf tubes. The Eppendorf
tubes were then stored in an incubator at 70 degrees C for 5 days. The Eppendorf
tubes were weighed to obtain the final weight of the Eppendorf tubes plus
extruded debris. Three consecutive weights were obtained for each tube. The
groups were compared using the Kruskal-Wallis one-way analysis of variance on
Ranks and Tukey's test. RESULTS: The ProTaper Next group produced the highest
mean extrusion value whilst WaveOne produced less debris compared with all the
other instruments (P > 0.05). There was a significant difference between the
ProTaper Next and WaveOne group (P < 0.05). CONCLUSIONS: Apically extruded debris
was associated with all instrumentation techniques. The WaveOne system extruded
less debris compared with the Twisted File and ProTaper Next.
PMID- 25112962
TI - The resemblance and disparity of gene expression in dormant and non-dormant seeds
and crown buds of leafy spurge (Euphorbia esula).
AB - BACKGROUND: Leafy spurge (Euphorbia esula L.) is a herbaceous perennial weed and
dormancy in both buds and seeds is an important survival mechanism. Bud dormancy
in leafy spurge exhibits three well-defined phases of para-, endo- and
ecodormancy; however, seed dormancy for leafy spurge is classified as
physiological dormancy that requires after-ripening and alternating temperature
for maximal germination. Overlaps in transcriptome profiles between different
phases of bud and seed dormancy have not been determined. Thus, we compared
various phases of dormancy between seeds and buds to identify common genes and
molecular processes, which should provide new insights about common regulators of
dormancy. RESULTS: Cluster analysis of expression profiles for 201 selected genes
indicated bud and seed samples clustered separately. Direct comparisons between
buds and seeds are additionally complicated since seeds incubated at a constant
temperature of 20 degrees C for 21 days (21d C) could be considered paradormant
(Para) because seeds may be inhibited by endosperm-generated signals, or
ecodormant (Eco) because seeds germinate after being subjected to alternating
temperature of 20:30 degrees C. Since direct comparisons in gene expression
between buds and seeds were problematic, we instead examined commonalities in
differentially-expressed genes associated with different phases of dormancy.
Comparison between buds and seeds ('Para to Endo buds' and '21d C to 1d C
seeds'), using endodormant buds (Endo) and dormant seeds (1d C) as common
baselines, identified transcripts associated with cell cycle (HisH4), stress
response/transcription factors (ICE2, ERFB4/ABR1), ABA and auxin response (ABA1,
ARF1, IAA7, TFL1), carbohydrate/protein degradation (GAPDH_1), and transport
(ABCB2). Comparison of transcript abundance for the 'Eco to Endo buds' and '21d C
to 1d C seeds' identified transcripts associated with ABA response (ATEM6), auxin
response (ARF1), and cell cycle (HisH4). These results indicate that the
physiological state of 21d C seeds is more analogous to paradormant buds than
that of ecodormant buds. CONCLUSION: Combined results indicate that common
molecular mechanisms associated with dormancy transitions of buds and seeds
involve processes associated with ABA and auxin signaling and transport, cell
cycle, and AP2/ERF transcription factors or their up-stream regulators.
PMID- 25112965
TI - Doping of wide-bandgap titanium-dioxide nanotubes: optical, electronic and
magnetic properties.
AB - Doping semiconductors is an important step for their technological application.
While doping bulk semiconductors can be easily achieved, incorporating dopants in
semiconductor nanostructures has proven difficult. Here, we report a facile
synthesis method for doping titanium-dioxide (TiO2) nanotubes that was enabled by
a new electrochemical cell design. A variety of optical, electronic and magnetic
dopants were incorporated into the hollow nanotubes, and from detailed studies it
is shown that the doping level can be easily tuned from low to heavily-doped
semiconductors. Using desired dopants - electronic (p- or n-doped), optical
(ultraviolet bandgap to infrared absorption in co-doped nanotubes), and magnetic
(from paramagnetic to ferromagnetic) properties can be tailored, and these
technologically important nanotubes can be useful for a variety of applications
in photovoltaics, display technologies, photocatalysis, and spintronic
applications.
PMID- 25112961
TI - Next-generation endomyocardial biopsy: the potential of confocal and super
resolution microscopy.
AB - Confocal laser scanning microscopy and super-resolution microscopy provide high
contrast and high-resolution fluorescent imaging, which has great potential to
increase the diagnostic yield of endomyocardial biopsy (EMB). EMB is currently
the gold standard for identification of cardiac allograft rejection, myocarditis,
and infiltrative and storage diseases. However, standard analysis is dominated by
low-contrast bright-field light and electron microscopy (EM); this lack of
contrast makes quantification of pathological features difficult. For example,
assessment of cardiac allograft rejection relies on subjective grading of H&E
histology, which may lead to diagnostic variability between pathologists. This
issue could be solved by utilising the high contrast provided by fluorescence
methods such as confocal to quantitatively assess the degree of lymphocytic
infiltrate. For infiltrative diseases such as amyloidosis, the nanometre
resolution provided by EM can be diagnostic in identifying disease-causing
fibrils. The recent advent of super-resolution imaging, particularly direct
stochastic optical reconstruction microscopy (dSTORM), provides high-contrast
imaging at resolution approaching that of EM. Moreover, dSTORM utilises
conventional fluorescence dyes allowing for the same structures to be routinely
imaged at the cellular scale and then at the nanoscale. The key benefit of these
technologies is that the high contrast facilitates quantitative digital analysis
and thereby provides a means to robustly assess critical pathological features.
Ultimately, this technology has the ability to provide greater accuracy and
precision to EMB assessment, which could result in better outcomes for patients.
PMID- 25112963
TI - Expression of the long-chain fatty acid receptor GPR120 in the gonadotropes of
the mouse anterior pituitary gland.
AB - G-protein-coupled receptor 120 (GPR120) has been known to be a receptor of long
chain fatty acids. Here, we investigated GPR120 expression in the mouse pituitary
gland via real-time PCR, in situ hybridization, and immunohistochemistry. GPR120
mRNA was abundantly expressed in the pituitary gland of ad-lib fed animals. In
situ hybridization and immunohistochemistry revealed GPR120 expression in the
gonadotropes of the anterior pituitary gland, but not in thyrotropes,
somatotropes, lactotropes, corticotropes, melanotropes, and the posterior
pituitary gland. Furthermore, 24 h of fasting induced an increase in GPR120 mRNA
expression in the pituitary gland. These results demonstrate that GPR120 in mouse
pituitary gonadotropes is upregulated by fasting and that it may play a role in
controlling gonadotropin secretion.
PMID- 25112966
TI - Wheelchair appropriateness in patients with spinal cord injury: a Turkish
experience.
AB - STUDY DESIGN: Descriptive. OBJECTIVE: To determine the wheelchair appropriateness
in patients with spinal cord injury (SCI). SETTING: National Rehabilitation
Center in Ankara, Turkey. METHODS: Twenty-seven (25 male, 2 female) SCI patients
were included. Demographic and clinical characteristics of the patients were
noted. All wheelchairs were evaluated considering each part (seat length, seat
depth, seat height, back height, armrest, headrest, wheels and seat belt) by a
physiatrist who had attended the wheelchair-training course. The wheelchair was
declared as inappropriate if at least three parts of wheelchair were not
appropriate. RESULTS: The mean age of the patients was 32.9+/-9.3 years and mean
duration of wheelchair use was 19.63+/-23.02 months. Among the patients, 21
(77.8%) were American Spinal Injury Association Impairment Scale (AIS) A, 4
(3.7%) AIS B, 1 (3.7%) AIS C and 1 (3.7%) AIS D. Five (18.5%) wheelchairs were
motorized and 22 (81.5%) were manual. Overall, 15 (55.6%) wheelchairs were
inappropriate. Seat height, cushion and back height were the most common
inappropriate parts. CONCLUSION: In light of our first and preliminary results,
we can argue that 55% of the patients with SCI use inappropriate wheelchairs. In
order to achieve better mobility; personally designed wheelchairs should be
prescribed by the clinicians.
PMID- 25112967
TI - Association of acute pancreatitis or high level of serum pancreatic enzymes in
patients with acute spinal cord injury: a prospective study.
AB - BACKGROUND: Spinal cord injuries has increased together with urban violence and
show a high rates of incidence. Besides the onus to patient and society, it can
also cause other serious complications to victims. Acute pancreatitis has an
important impact on this disease and has been underdiagnosed in several patients.
OBJECTIVES: The aim of this study was investigate the association of acute
pancreatitis in acute spinal cord injuries. The secondary aim was to propose an
investigation protocol to early diagnose and prevent it. METHODS: A prospective
observational study was conducted in 78 patients who presented acute spinal cord
injury (SCI) at our emergency department, confirmed by clinical and imaging
examination, in according to the American Spinal Injury Association (ASIA)
Classification. Exclusion criteria were chronic or associate diseases in spinal
cord, pancreatic direct trauma, alcoholism and chronic pancreatic disease.
RESULTS: The association of acute pancreatitis in patients with SCI was 11.53%.
The occurrence of pancreatitis or high levels of serum pancreatic enzymes in
patients with ASIA A was 41.7% and only 4.17% in patients with ASIA E. In all,
55.2% of patients who presented pancreatitis or high levels of serum pancreatic
enzymes had cervical level of SCI and 34.5% had thoracic level. Adynamic ileus
was observed in 68.96% of this group. CONCLUSION: We concluded that, in acute
spinal cord injuries, the occurrence of acute pancreatitis or high serum levels
of pancreatic enzymes are more frequent in patients with ASIA A Classification,
cervical/thoracic level of spinal injury and adynamic ileus.
PMID- 25112968
TI - Centralized spinal cord injury care in Finland: unveiling the hidden incidence of
traumatic injuries.
AB - STUDY DESIGN: Population-based prospective study. OBJECTIVES: To determine the
incidence and evaluate the characteristics of newly injured patients with
traumatic spinal cord injury (TSCI) admitted to two of the three national spinal
cord injury (SCI) centers during the first year after the centralization of SCI
care in Finland. SETTING: Oulu and Tampere University Hospital SCI centers,
Finland. METHODS: The designated rehabilitation teams evaluated all of the
patients with a new SCI and persisting neurological symptoms. The data were
recorded according to the International Spinal Cord Injury Core Data Set.
RESULTS: In a 1-year period, 77 new patients with TSCI were admitted to the study
centers serving a population of 3 065 946. In the whole catchment area, the mean
annual incidence of TSCI was 25.1 per million, and in the hospital districts of
the SCI centers, the incidence was even higher, at 38.1 per million. The mean age
of the patients was 58.7 years. Falls were the leading cause of injury (64.9%),
and the injury resulted in tetraplegia in 70.1% of the cases. Alcohol use was a
contributing factor in 39% of the cases in the entire sample and in 58.6% of
cases among patients aged younger than 60 years. CONCLUSION: The incidence rates
of TSCI were markedly higher than expected, demonstrating the previously hidden
morbidity. The epidemiological features of TSCI appeared to follow the trends in
developed countries, highlighting the increasing incidence of cervical lesions
due to falling among the elderly. The results need to be confirmed in an extended
follow-up.
PMID- 25112969
TI - Intermittent catheterization in patients with traumatic spinal cord injury:
obstacles, worries, level of satisfaction.
AB - OBJECTIVES: The aim of this study is to examine the obstacles in people with
traumatic spinal cord injury (SCI) face performing intermittent catheterization
(IC), also their worries and level of satisfaction. METHODS: Two hundred sixty
nine patients performing IC for at least 3 months were asked to fill-out a
questionnaire about their opinions on IC. RESULTS: In total, 69.5% of patients
performed IC themselves, 10.4% had performed by their mothers, 7.8% by another
caregiver and 7.4% by their spouse. For the 72 (26%) patients unable to apply IC,
reasons were insufficient hand function (56.1%), being unable to sit
appropriately (35.4%) and spasticity (8.5%). In all, 70% of male patients had
insufficient hand function, 20% could not sit and 10% had spasticity while 56.3%
of female patients could not sit, 37.5% had insufficient hand function and 63%
had spasticity. Difference between sexes was found to be statistically
significant (P<0.05). Worries patients had when starting IC were fear of being
dependent on IC (50.2%), accidentally injuring self (43.8%), embarrassment
(43.2%), causing an infection (40.2%), bleeding (32.7%), fear of feeling pain
(30.2%) and hygiene (24.7%). More women felt embarrassment; other items were
similar in both sexes. In all, 46.9% of patients had urinary incontinence in
intervals. CONCLUSION: In total, 69.5% of patients performed IC themselves. Men's
most common obstacle was insufficient hand function while women's was being
unable to sit appropriately. Patients' most common worries were being dependent
on IC for life. In all, 46.9% had incontinence in intervals; 47.9% said IC
improved their life quality; and 97.4% preferred IC over continuous
catheterization.
PMID- 25112970
TI - rTMS modulates reciprocal inhibition in patients with traumatic spinal cord
injury.
AB - STUDY DESIGN: Randomized, double-blind, crossover, sham-controlled trial.
OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) over the primary
motor cortex (M1) leads to a significant reduction of spasticity in subjects with
spinal cord injury (SCI), but the physiological basis of this effect is still not
well understood. The purpose of this study was to evaluate the disynaptic
reciprocal Ia inhibition of soleus motoneurons in SCI patients. SETTING:
Department of Neurology, Merano, Italy and TMS Laboratory, Paracelsus Medical
University, Salzburg, Austria. METHODS: Nine subjects with incomplete cervical or
thoracic SCI received 5 days of daily sessions of real or sham rTMS applied over
the contralateral M1. We compared the reciprocal inhibition, the Modified
Ashworth Scale and the Spinal Cord Injury Assessment Tool for Spasticity at
baseline, after the last session and 1 week later in the real rTMS and sham
stimulation groups. RESULTS: We found that real rTMS significantly reduced lower
limb spasticity and restored the impaired excitability in the disynaptic
reciprocal inhibitory pathway. CONCLUSIONS: In a small proof-of-concept study,
rTMS strengthened descending projections between the motor cortex and inhibitory
spinal interneuronal circuits. This reversed a defect in reciprocal inhibition
after SCI, and reduced leg spasticity.
PMID- 25112971
TI - Thioetherification of chloroheteroarenes: a binuclear catalyst promotes wide
scope and high functional-group tolerance.
AB - A constrained binuclear palladium catalyst system affords selective
thioetherification of a wide range of functionalized arenethiols with
chloroheteroaromatic partners with the highest turnover numbers (TONs) reported
to date and tolerates a large variety of reactive functions. The scope of this
system includes the coupling of thiophenols with six- and five-membered 2
chloroheteroarenes (i.e., functionalized pyridine, pyrazine, quinoline,
pyrimidine, furane, and thiazole) and 3-bromoheteroarenes (i.e., pyridine and
furane). Electron-rich congested thiophenols and fluorinated thiophenols are also
suitable partners. The coupling of unprotected amino-2-chloropyridines with
thiophenol and the successful employment of synthetically valuable
chlorothiophenols are described with the same catalyst system. DFT studies
attribute the high performance of this binuclear palladium catalyst to the
decreased stability of thiolate-containing resting states. Palladium loading was
as low as 0.2 mol %, which is important for industrial application and is a step
forward in solving catalyst activation/deactivation problems.
PMID- 25112972
TI - Calibrating corneal material model parameters using only inflation data: an ill
posed problem.
AB - Goldmann applanation tonometry (GAT) is a method used to estimate the intraocular
pressure by measuring the indentation resistance of the cornea. A popular
approach to investigate the sensitivity of GAT results to material and geometry
variations is to perform numerical modelling using the finite element method, for
which a calibrated material model is required. These material models are
typically calibrated using experimental inflation data by solving an inverse
problem. In the inverse problem, the underlying material constitutive behaviour
is inferred from the measured macroscopic response (chamber pressure versus
apical displacement). In this study, a biomechanically motivated elastic fibre
reinforced corneal material model is chosen. The inverse problem of calibrating
the corneal material model parameters using only experimental inflation data is
demonstrated to be ill-posed, with small variations in the experimental data
leading to large differences in the calibrated model parameters. This can result
in different groups of researchers, calibrating their material model with the
same inflation test data, drawing vastly different conclusions about the effect
of material parameters on GAT results. It is further demonstrated that multiple
loading scenarios, such as inflation as well as bending, would be required to
reliably calibrate such a corneal material model.
PMID- 25112973
TI - Melatonin promotes seed germination under high salinity by regulating antioxidant
systems, ABA and GA4 interaction in cucumber (Cucumis sativus L.).
AB - Although previous studies have found that melatonin can promote seed germination,
the mechanisms involved in perceiving and signaling melatonin remain poorly
understood. In this study, it was found that melatonin was synthesized during
cucumber seed germination with a peak in melatonin levels occurring 14 hr into
germination. This is indicative of a correlation between melatonin synthesis and
seed germination. Meanwhile, seeds pretreated with exogenous melatonin (1 MUM)
showed enhanced germination rates under 150 mM NaCl stress compared to water
pretreated seeds under salinity stress. There are two apparent mechanisms by
which melatonin alleviated salinity-induced inhibition of seed germination.
Exogenous melatonin decreased oxidative damage induced by NaCl stress by
enhancing gene expression of antioxidants. Under NaCl stress, compared to
untreated control, the activities of antioxidant enzymes including superoxide
dismutase (SOD), catalase (CAT), and peroxidase (POD) were significantly
increased by approximately 1.3-5.0-fold, with a concomitant 1.4-2.0-fold increase
of CsCu-ZnSOD, CsFe-ZnSOD, CsCAT, and CsPOD in melatonin-pretreated seeds.
Melatonin also alleviated salinity stress by affecting abscisic acid (ABA) and
gibberellin acid (GA) biosynthesis and catabolism during seed germination.
Compared to NaCl treatment, melatonin significantly up-regulated ABA catabolism
genes (e.g., CsCYP707A1 and CsCYP707A2, 3.5 and 105-fold higher than NaCl
treatment at 16 hr, respectively) and down-regulated ABA biosynthesis genes
(e.g., CsNECD2, 0.29-fold of CK2 at 16 hr), resulting in a rapid decrease of ABA
content during the early stage of germination. At the same time, melatonin
positively up-regulated GA biosynthesis genes (e.g., GA20ox and GA3ox, 2.3 and
3.9-fold higher than NaCl treatment at 0 and 12 hr, respectively), contributing
to a significant increase of GA (especially GA4) content. In this study, we
provide new evidence suggesting that melatonin alleviates the inhibitory effects
of NaCl stress on germination mainly by regulating the biosynthesis and
catabolism of ABA and GA4.
PMID- 25112974
TI - Epidemiology of Wilson's disease in Ireland.
PMID- 25112976
TI - Revisionary checklist of the Southern African Sesiini (Lepidoptera: Sesiidae)
with description of new species.
AB - A revisionary checklist of the Sesiini of southern Africa is presented. All known
genera of the region and their type species are redescribed. The following genera
are placed in Sesiini for the first time: Alonina Walker, 1856; Anaudia
Wallengren, 1863; Austrosetia Felder & Felder, 1874; Megalosphecia Le Cerf, 1916
and Vespanthedon Le Cerf, 1917. The genera Cicinnoscelis Holland, 1893 rev. stat.
(from synonymy with Alonina Walker, 1856) and Felderiola Naumann, 1971 rev. stat.
(from synonymy with Monopetalotaxis Wallengren, 1859) are resurrected from
synonymy and included in Sesiini. One new genus, Hagnogyna new gen., and seven
new species, Cicinnoscelis flavipes new sp., C. krooni new sp., Alonina rufa new
sp., A. fusca new sp., Anaudia thyranthrena new sp., Felderiola karooensis new
sp. and F. xanthogaster new sp., are described. The following new combinations
are introduced: Cicinnoscelis longipes Holland, 1893 rev. comb., Alonina pyrethra
(Hampson, 1919) new comb., A. pyrocraspis (Hampson, 1910) new comb., A.
luteopunctata (Freina, 2011) new comb., Felderiola candescens (Felder & Felder,
1874) rev. comb., Hagnogyna sanguicosta (Hampson, 1919) new comb., H. bartschi
(Freina, 2011) new comb. and Vespanthedon chalciphora (Hampson, 1919) new comb.
Alonina difformis Hampson, 1919 new syn. is considered a subjective junior
synonym of A. rygchiiformis Walker, 1856. A lectotype is designated for
Austrosetia semirufa Felder & Felder, 1874 and the previously unknown males of
this species and of Anaudia felderi Wallengren, 1863 are described. Bionomical
data for some of the species discussed are given for the first time.
PMID- 25112975
TI - Epigenetic promoter silencing in Friedreich ataxia is dependent on repeat length.
AB - OBJECTIVE: Friedreich ataxia (FRDA) is caused by an expanded GAA triplet-repeat
(GAA-TR) mutation in the FXN gene. Patients are typically homozygous for expanded
alleles containing 100 to 1,300 triplets, and phenotypic severity is
significantly correlated with the length of the shorter of the 2 expanded
alleles. Patients have a severe deficiency of FXN transcript, which is
predominantly caused by epigenetic silencing of the FXN promoter. We sought to
determine whether the severity of FXN promoter silencing is related to the length
of the expanded GAA-TR mutation in FRDA. METHODS: Patient-derived lymphoblastoid
cell lines bearing a range of expanded alleles (200-1,122 triplets) were
evaluated for FXN transcript levels by quantitative reverse transcriptase
polymerase chain reaction. FXN promoter function was directly measured by
quantitative analysis of transcriptional initiation via metabolic labeling of
newly synthesized transcripts in living cells. RESULTS: FXN transcriptional
deficiency was significantly correlated with the length of the shorter of the 2
expanded alleles, which was noted both upstream (R(2) = 0.84, p = 0.014) and
downstream (R(2) = 0.89, p = 0.002) of the expanded GAA-TR mutation, suggesting
that FXN promoter silencing in FRDA is related to repeat length. A bilinear
regression model revealed that length dependence was strongest when the shorter
of the 2 expanded alleles contained <400 triplets. Direct measurement of FXN
promoter activity in patients with expanded alleles containing <400 versus >400
triplets in the shorter of the 2 expanded alleles revealed a significantly
greater deficiency in individuals with longer GAA-TR alleles (p < 0.05).
INTERPRETATION: FXN promoter silencing in FRDA is dependent on the length of the
expanded GAA-TR mutation.
PMID- 25112977
TI - Redefinition of the millipede subgenus Megaphyllum sensu stricto Verhoeff, 1894
and neotype designation for Megaphyllum austriacum (Latzel, 1884) (Myriapoda:
Diplopoda: Julida: Julidae).
AB - Megaphyllum sensu stricto, i.e. the nominotypical subgenus of the very
complicated genus Megaphyllum Verhoeff, 1894, is redefined on the basis of
examination of type and non-type material and literature data. Four species
groups including twenty species in all are listed, and the identity of M.
austriacum (C. L. Koch, 1838) is clarified with a proposal of neotype designation
under ICZN Article 75.6. in order to stabilize the current usage of the name.
Prevailing usage of M. silvaticum (Verhoeff, 1898) syn. nov. (nomen protectum)
over the senior synonym M. nigrescens (Latzel, 1884) (nomen oblitum) is
maintained under ICZN Article 23.9. M. banaticum (Verhoeff, 1899) is syn. nov. of
M. erythronotum (Latzel, 1884) comb. nov., M. bosniense cotinophilum (Loksa,
1962) syn. nov. of M. bosniense bosniense (Verhoeff, 1897) and M. transsylvanicum
transdanubicum (Loksa, 1962) syn. nov. of M. transsylvanicum transsylvanicum
(Verhoeff, 1897). M. unilineatum (C. L. Koch, 1838) is new to the fauna of
Turkey.
PMID- 25112979
TI - Phamartes coronatus gen. nov. sp. nov. a new genus and species of stick insect
from Bach Ma National Park, central Vietnam (Phasmida, Diapheromeridae,
Necrosciinae).
AB - A new genus and species of stick insect Phamartes coronatus gen. nov. sp. nov.
from Bach Ma National Park, central Vietnam is described and illustrated from
both sexes and the egg. The genus is most closely related to Oxyartes Stal, 1875,
but easily distinguishable by the presence of fully developed alae, the head
armature and the split and asymmetrical anal segment, a character previously
unknown in Necrosciinae.
PMID- 25112978
TI - Nematodes from galls on Myrtaceae. V. Fergusobia from large multilocular shoot
bud galls from Angophora and Eucalyptus in Australia, with descriptions of six
new species.
AB - Six new species of Fergusobia, from large multilocular shoot bud galls on two
species of Angophora and four species of Eucalyptus from both subgenera
Eucalyptus and Symphyomyrtus, are described. Fergusobia cosmophyllae Davies n.
sp. is characterized by the combination of a C-shaped parthenogenetic female with
a short arcuate conoid tail, a broad (small a ratio) arcuate infective female
with an hemispherical tail tip, and an arcuate to J-shaped male with broad,
angular spicules and short bursa. Fergusobia delegatensae Davies n. sp. has an
open C-shaped parthenogenetic female with a broadly conoid tail, an infective
female of variable shape with an hemispherical tail tip, and a male of open C
shape with a crenate bursa that arises 40-70% along the length of the body from
the tail tip and terminates just anterior to the cloaca. Fergusobia diversifoliae
Davies n. sp. has a C-shaped parthenogenetic female with a conoid tail, an
arcuate infective female with a hemispherical tail tip, and an arcuate, C- or J
shaped male with angular spicule and a long peloderan bursa. Fergusobia
floribundae Davies n. sp. has a C-shaped parthenogenetic female with a narrow,
arcuate, conoid tail, an arcuate infective female with a hemispherical tail tip,
and an arcuate or J-shaped male with an angular spicule and a short to mid-body
length peloderan bursa. Fergusobia minimus Lisnawita n. sp. has a C-shaped
parthenogenetic female with a conoid tail, an arcuate to open C-shaped infective
female with a hemispherical tail tip, and an arcuate to open C-shaped male with
an angular spicule and a peloderan bursa arising at about 10-30% of body length.
Fergusobia pimpamensis Davies n. sp. has an open C to C-shaped parthenogenetic
female with a narrow conoid tail, an arcuate to open C-shaped infective female
with a hemispherical tail tip, and an arcuate to C-shaped male with an arcuate
spicule and a long, crenate, peloderan bursa. An inventory of all known
Fergusobia/Fergusonina associations from terminal shoot bud galls is presented.
The larval shield morphology of the associated mutualistic Fergusonina species is
discussed where known. Analyses of DNA sequences of D2/D3 and COI suggested that
the six new species are distributed between three clades of Fergusobia.
PMID- 25112981
TI - A new species of Gamasiphis Berlese (Acari: Ologamasidae) from Russia (Sakhalin
and Kuril Islands) with a key to the Asian species .
AB - Gamasiphis ochotensis sp. n. is described based on the morphology of females and
males collected from litter and soil in the Sakhalin and Kuril Islands of Far
East Russia. A key for the separation of females of 10 recognisable species of
Gamasiphis distributed in Asia is provided.
PMID- 25112980
TI - Nematodes from galls on Myrtaceae. IV. Fergusobia from flat leaf galls on
Eucalyptus and Corymbia, with descriptions of two new species.
AB - Two new species of Fergusobia are described. Both were collected from flat leaf
galls from South Australia, one on Eucalyptus microcarpa and the other on E.
porosa. Fergusobia microcarpae n. sp. Davies is characterised by the combination
of a C-shaped parthenogenetic female with a short, broadly rounded conoid tail,
an arcuate to open C-shaped infective female with an hemispherical tail tip, and
arcuate to J-shaped males with angular spicules and short peloderan bursa.
Fergusobia porosae n. sp. Davies is similar in having an arcuate to C-shaped
parthenogenetic female with a small conoid tail, an almost straight to arcuate
infective female with an hemispherical tail tip, and males that are almost
straight to barely J-shaped with angular spicules and short peloderan bursa. They
differ in that the bodies of parthenogenetic and infective females of F.
microcarpae n. sp. are more curved than in F. porosae n. sp. Other known similar
forms of Fergusobia/Fergusonina galls are outlined and the larval shield
morphologies of their associated mutualistic Fergusonina fly species are
discussed where known. An inventory of all known Fergusobia/Fergusonina
associations from flat leaf galls from Corymbia spp. and Eucalyptus spp. is
presented. Relationships of Fergusobia nematodes were inferred from analysis of
sequences of 28S rDNA D2/D3 domains and a portion of mitochondrial DNA cytochrome
oxidase subunit I (mtCOI). Nematodes from flat leaf galls appeared in two clades.
PMID- 25112982
TI - Species diversity in the Palaeotropical leaf-litter genus Apelaunothrips
(Thysanoptera, Phlaeothripinae).
AB - Species of Apelaunothrips are fungus-feeders on dead leaves, particularly in leaf
litter, and they are recorded across the Old World tropics from Africa to
northern Australia and southern Japan. All species in this genus have the
maxillary stylets 4-6 microns in diameter, considerably broader than the 2-3
micron diameter that is typical among Phlaeothripinae. The species are largely
uniform in structure, but in four species the larger males have fore femora
enlarged with a conspicuous tubercle on the inner margin at the base. In one of
these species, the males are dimorphic, with no intermediates between large and
small individuals, in contrast to the continuous variation in structure found in
many polymorphic Phlaeothripidae. A key is provided to the 37 recognised species
of Apelaunothrips, including the following: A. desleyae sp.n. from northern
Australia; A. bogor sp.n. from Java; A. gombak sp.n. from Peninsular Malaysia.
PMID- 25112983
TI - A new, prairie-restricted species of Anacampsis Curtis (Lepidoptera: Gelechiidae)
from Illinois .
AB - Anacampsis wikeri (Lepidoptera: Gelechiidae), new species, is described. The
larva of A. wikeri feeds on leaves of a prairie legume, leadplant, Amorpha
canescens (Fabaceae). The moth is univoltine, with mature larvae occurring in
late May; adults are active from early June into summer and autumn, while
overwintering throughout the winter months. The adult of A. wikeri is externally
very similar to that of another legume-feeding species, Anacampsis psoraliella.
Sight identification of adults of these two species, especially of unreared
individuals originating in the multi-state area of the Midwest in which their
respective larval hostplants are sympatric, therefore is rendered problematic.
Larval host plant specificity and adult genital morphology, however, allow
unequivocal diagnosis. These characters are discussed, and male and female
genitalia are illustrated for both species.
PMID- 25112984
TI - Systematics, phylogeny and biology of a new genus of Lithocolletinae
(Lepidoptera: Gracillariidae) associated with Cistaceae.
AB - The gracillariid genus Triberta gen. nov. (Lepidoptera: Gracillariidae:
Lithocolletinae Stainton, 1854) is described to accommodate two species formerly
assigned to the genus Phyllonorycter Hubner, 1822: Triberta helianthemella
(Herrich-Schaffer, 1861) comb. nov. and T. cistifoliella (Groschke, 1944) comb.
nov. Triberta cistifoliella bona sp. is restored from synonymy based on
morphological characters. The new genus is biologically associated with the plant
family Cistaceae of the order Malvales and is endemic to the Palaearctics. Our
molecular analysis of eleven nuclear genes failed to unambiguously place Triberta
in the lithocolletine phylogeny, but revealed that this genus is distinct from
either clade Phyllonorycter + Cremastobombycia and Cameraria. The distinctiveness
of Triberta is also supported by inferred traits in wing venation, micro
morphology of the last instar larva, pupa, genital morphology of the adult and
life history. A key to the species of Triberta is provided. The interspecific
homogeneity in external morphology, coupled with minor differences in genital
traits, an apparent narrow specialization on Cistaceae host plants, restricted
geographical range and molecular evidence based on multi-nuclear genes jointly
suggest that the generic diversification of Triberta is a relatively old
phenomenon and driven strongly by host selection.
PMID- 25112985
TI - A new genus and species of Leptocheliidae (Crustacea: Peracarida: Tanaidacea)
from Isla del Coco (Costa Rica).
AB - Samples from the scarcely-studied sedimentary seabed from the Isla del Coco
(Costa Rica) yielded a single species of Tanaidacea, belonging to a new genus of
Leptocheliidae, Cocotanais. The new genus shows affinities with Pseudonototanais
and Heterotanais in bearing a conspicuous forcipate cheliped in the males, which
in Cocotanais has a modified merus and carpal flange. Other distinct characters
of the males are a triangular cephalothorax, a three-articled antennular peduncle
and swollen bases of pereopods 4-6. Females have a four-articled antennule, a
maxilliped endite with three distal flat spines and two inner coupling hooks, and
a maxilliped basis with two long setae. The species was found in sheltered bays,
both free-living in the sediment and also as a commensal of anemones (Infraorder
Boloceroidaria), thus representing the first reported case of such an
association.
PMID- 25112987
TI - Discovery of four new species of the genus Planaeschna from Southwestern China
(Odonata: Anisoptera: Aeshnidae).
AB - Four new species of the genus Planaeschna, P. robusta sp. nov. (holotype male;
Mt. Emeishan, Emeishan City, Sichuan Province, China, 16. VIII. 2007), P.
maculifrons sp. nov. (holotype male; Mt. Emeishan, Emeishan City, Sichuan
Province, China, 20. VIII. 2007), P. caudispina sp. nov. (holotype male; Mt.
Qingchengshan, Dujiangyan City, Sichuan Province, China, 30. VIII. 2007) and P.
monticola sp. nov. (holotype male; Sanjiacun Stream, Fengyi Town, Dali City,
Yunnan Province, China, 19. XI. 2012) are described and illustrated and diagnosed
from their congeners. All the holotypes have been deposited in the Collection of
Aquatic Animals, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan
City, Hubei Province, China. Brief notes on the biology of each species are also
provided.
PMID- 25112988
TI - Description of larva, redescription of adults and biology of Mortogenesia
mesopotamica (Morton, 1921) (Ephemeroptera: Palingeniidae).
AB - All life stages of Mortogenesia mesopotamica (Morton, 1921) are described, on the
basis of material collected in the lower Euphrates-Tigris River basin. Adults are
redescribed, and larvae are described for the first time, based on sets of larval
exuviae. The monotypic genus Mortogenesia Lestage, 1923 is redefined using both
adult and larval characteristics: eyes not contiguous, distinctly separated by a
wide gap; vestigial mandibular tusks present, with 3-4 rounded lateral
projections; forewing veins MP1 and iMP not brought together; CuA
furcation absent on forewing; both claws similarly shaped in males; hind tarsi
five-segmented; penes with roughly triangular, apically rounded and divergent
lobes (in adults); seven conspicuous stout teeth on outer margin of mandibular
tusk, with no apical spine-like setae; maxillary palps two-segmented; distal
segment of labial palps asymmetric and bulbous; basal segment of labial palps
densely pilose; forelegs with relatively short, triangular claws that are basally
wider than tarsi; foretibiae with stout spines only; and a simple, leaf-like gill
1 (in larvae). The burrowing larvae of M. mesopotamica occur solely in large
permanent lowland rivers, in clayey or muddy sediments, with particles exceeding
0.025-0.075 mm. Based on observations of their burrows, larval density is
approximately 100-200 individuals per square meter. Various evidence suggests a
unique phenomenon of male neoteny in Mortogenesia. Preliminary results of male
dissections suggests a missing teneral adult cuticle, and male "subimagoes" and
females occur simultaneously after oviposition. Mortogenesia mesopotamica is
known currently from the Euphrates-Tigris basin in Iraq and from the Karkheh
River in Iran.
PMID- 25112989
TI - New pseudophyllinae from the Lesser Antilles (Orthoptera: Ensifera:
Tettigoniidae).
AB - Two new Cocconitini Brunner von Wattenwyl, 1895 species belonging to Nesonotus
Beier, 1960 are described from the Lesser Antilles: Nesonotus caeruloglobus
Hugel, n. sp. from Dominica, and Nesonotus vulneratus Hugel, n. sp. from
Martinique. The songs of both species are described and elements of biology are
given. The taxonomic status of species close to Nesonotus tricornis (Thunberg,
1815) is discussed.
PMID- 25112986
TI - Pachybrachis holerorum (Coleoptera: Chrysomelidae: Cryptocephalinae), a new
species from the Apennines, Italy, identified by integration of morphological and
molecular data.
AB - Pachybrachis holerorum n. sp. is described from the northern Apennines, Italy.
The new species is related to P. karamani (Weise, 1893), from which it differs in
the shape of the median lobe of the aedeagus and in small differences in
chromatic pattern. The close relationship with P. karamani is confirmed by
molecular analyses performed on a fragment of 829 nucleotides of the
mitochondrial gene Cytochrome c oxidase subunit 1 (cox1). The general mixed Yule
coalescent model, developed for species delimitation using single-locus molecular
data, was applied to a cox1 phylogeny in order to test the hypothesis of P.
holerorum as a separate species. Information on the host plants, acquired during
specimen collection, was confirmed from gut content, targeting a fragment of the
plastid large subunit of the ribulose-bisphosphate carboxylase gene and the
trnL(UAA) intron. Besides, the lectotype of P. karamani is designated.
PMID- 25112990
TI - The Phyllomedusa perinesos group (Anura: Hylidae) is derived from a Miocene
Amazonian Lineage.
AB - The Phyllomedusa perinesos group is composed of four species that inhabit cloud
forests in the eastern Andean slopes. We estimated the phylogenetic relationships
among them and their closest relatives using mitochondrial DNA sequences. Our
results confirm the monophyly of the group and a close relationship with the
Amazonian species Phyllomedusa atelopoides and Phyllomedusa tomopterna. A
chronogram indicates that the group originated during the Miocene and the
contemporary species diverged from their closest relatives during the Miocene and
early Pliocene. The timing of the group's origin suggests that its evolution was
linked to the rise of the eastern Andes. Based on the phylogeny we expand the
species content of the group to include P. atelopoides and P. tomopterna.
PMID- 25112991
TI - Why Drosophila is not Drosophila any more, why it will be worse and what can be
done about it?
PMID- 25112992
TI - Tersilochinae of Western Amazonia (Hymenoptera: Ichneumonidae). Genus Stethantyx
Townes, part 1.
AB - Sixteen species of the genus Stethantyx Townes having first and second sections
of radius meeting at obtuse angle are recorded from Peru and Ecuador in Western
Amazonia. Ten species, S. amazonica Khalaim & Saaksjarvi, sp. nov., S. aurantia
Khalaim & Saaksjarvi, sp. nov., S. juninensis Khalaim & Bordera, sp. nov., S.
loretosa Khalaim & Saaksjarvi, sp. nov., S. neopropodeator Khalaim & Saaksjarvi,
sp. nov., S. orellana Khalaim & Saaksjarvi, sp. nov., S. sinuata Khalaim &
Saaksjarvi, sp. nov., S. tiputinia Khalaim & Saaksjarvi, sp. nov., S. trepida
Khalaim & Saaksjarvi, sp. nov. and S. voluptaria Khalaim & Saaksjarvi, sp. nov.,
are described as new. Six species, previously known only from Costa Rica, S.
alajuela Khalaim & Broad, S. heredia Khalaim & Broad, S. orosia Khalaim & Broad,
S. propodeator Khalaim & Broad, S. puntarenasa Khalaim & Broad and S. sanjosea
Khalaim & Broad, are recorded from South America for the first time. A partial
key to Western Amazonian species of Stethantyx is given.
PMID- 25112993
TI - Makoiamya cotterallae, a new genus and species of bivalve (Ceratomyidae) from the
latest Triassic of New Zealand and New Caledonia.
AB - The new genus and species Makoiamya cotterallae is erected for fossil bivalves
previously informally identified as Anodontophora Alberti (= Unionites Wissmann)
or a relative or Ochotomya Polubotko in the Late Triassic Murihiku Terrane of New
Zealand and Teremba Terrane of New Caledonia (Norian and Rhaetian; Warepan and
Otapirian local stages). Neither of these genera happily accommodates these
shells and a new genus is considered necessary for them. Makoiamya fits most
readily into the Ceratomyidae and members were burrowers in fine sand and silt,
where they are generally preserved in life orientation.
PMID- 25112994
TI - New species and new records of the hygropetric water beetle genus Oocyclus Sharp
from South America (Coleoptera: Hydrophilidae).
AB - Three new species of Oocyclus Sharp, 1882 are described from tropical South
America: O. maluz sp. n. (Venezuela), O. miza sp. n. (Venezuela), and O. brunneus
sp. n. (Bolivia). New distributional records are provided for O. andinus Short &
Garcia, O. coromoto Short & Garcia (newly recorded from Suriname), O. floccus
Short & Garcia (newly recorded from Guyana and Suriname), O. iguazu (Oliva), O.
meridensis Short & Garcia, O. petra Short & Garcia (newly recorded from Guyana
and Suriname), O. trio Short & Kadosoe (newly recorded from Guyana), O. trujillo
Short & Garcia, and O. yubai Clarkson & Short (newly recorded from Paraguay).
Updates to the keys of the Brazilian and Venezuelan Oocyclus species are
provided.
PMID- 25112995
TI - Fecenia travancoria Pocock is recognised as a junior synonym of Fecenia protensa
Thorell (Araneae: Psechridae): a case of intraspecific variation .
PMID- 25112996
TI - Armadillogorgia albertoi sp. nov.: a new primnoid from the Argentinean deep sea.
AB - Eleven specimens of a new species of primnoid from the Argentinean deep sea are
here presented. Armadillogorgia albertoi sp. nov. differs from A. cyathella
Bayer, 1980 in colony and polyp morphology, abaxial sclerite number and shape. It
is the second species of the hitherto monospecific genus, and the northernmost
record of the genus.
PMID- 25112997
TI - Description of a new species of the genus Neolucanus Thomson, 1862 (Coleoptera:
Lucanidae) from central Vietnam.
AB - Neolucanus baongocae new species is described from Lam Dong Province (Central
Vietnam) and compared to closely related Neolucanus taxa.
PMID- 25112999
TI - Two species of Thienemanniella Kieffer from Oriental China (Diptera:
Chironomidae: Orthocladiinae).
AB - A new species from Oriental China, Thienemanniella curva sp. n. is described and
illustrated as adult males. T. nipponica which belong to eye bare species group
in Thienemanniella from Guangdong Province is re-described. A revised key to
known males of the world is provided.
PMID- 25112998
TI - Redescription of Osmylus multiguttatus McLachlan, 1870 (Neuroptera: Osmylidae)
with distributional remarks.
AB - Osmylus multiguttatus McLachlan, 1870 has recently been rediscovered in the
Middle Anatolia. Redescription of the male and female is presented. Faunistic
data and habitat are provided. Photograph of wings, drawings of male and female
external and internal genitalia are illustrated for the first time. The
distribution map with new recording sites and recent data is also given. A
preliminary key to species of Osmylus is presented.
PMID- 25113000
TI - A replacement name for Macrobrachium aemulum madhusoodani Pillai & Unnikrishnan,
2013, a junior homonym of Macrobrachium madhusoodani Unnikrishnan, Pillai &
Jayachandran, 2011 (Decapoda: Palaemonidae) .
PMID- 25113002
TI - Phylogenetic relationships of Tectoribates: nymphal characters of new North
American species place the genus in Tegoribatidae (Acari, Oribatida).
AB - Species in the oribatid mite genus Tectoribates are primarily Palaearctic and
Neotropical, with scattered, unidentified records from North America. Herein, we
describe 3 new Tectoribates species from dry forest and prairie habitats in North
America: T. alcecampestris sp. nov., from Alberta, T. borealis sp. nov., from
southern Alberta and Ontario, both on the basis of adults and nymphs, and T.
campestris sp. nov., from dry grassland habitats in Ontario and Kansas, on the
basis of adults. We provide a revised and expanded diagnosis for adults of
Tectoribates. We assess relationships of Tectoribates, using characters of adults
and newly discovered apheredermous, plicate immatures. We include observations on
Pseudotectoribates which is closely related to Tectoribates. The closest
relatives of these genera are hypothesised to be among the Tegoribatidae
(Achipterioidea) rather than among the Achipteriidae (Achipterioidea),
Oribatellidae (Oribatelloidea), or Ceratozetoidea, as suggested in previous
classifications. Finally, we give a key to adults of the world fauna of
Tectoribates.
PMID- 25113003
TI - A revision of the New World sharpshooter genus Xyphon Hamilton (Hemiptera:
Cicadellidae: Cicadellinae).
AB - A phylogenetic analysis of Xyphon was completed using 45 adult morphological
characters and 1,076 base pairs of the mtDNA gene NADH dehydrogenase 1. Multiple
specimens, representative of the range of morphological variation found in each
previously described species, were scored for the morphological data matrix to
test the monophyly of each species. These tests supported the following
synonymies: Xyphon gillettei (Ball, 1901) to include X. balli (Knull, 1940) syn.
nov.; and X. reticulatum (Signoret, 1854) to include X. diductum (Fowler, 1900)
syn. nov., X. dyeri (Gibson, 1919) syn. nov., and X. sagittiferum (Uhler, 1895)
syn. nov. Parsimony and Bayesian techniques were used to infer relationships
among species, resulting in almost identical tree topologies. In all analyses
Xyphon was monophyletic and Draeculacephala was its sister genus although clade
support for Xyphon was generally low. The analyses suggest that a clade
comprising X. flaviceps (Riley) and X. fulgidum (Nottingham) is sister to the
remainder of the genus, and a clade comprising X. gillettei and X. spadice sp.
nov. was sister to a clade containing X. triguttatum (Nottingham), X. nudum
(Nottingham), and X. reticulatum. The six currently recognized species, including
X. spadice sp. nov., are described and illustrated and a key to adult Xyphon is
provided.
PMID- 25113001
TI - Using various lines of evidence to identify Chironomus species (Diptera:
Chironomidae) in eastern Canadian lakes.
AB - Chironomus Meigen (Diptera, Chironomidae) larvae are usually the largest sediment
burrowing chironomids, and as such often constitute a major part of the
freshwater infaunal biomass. However, use of this genus in ecological,
environmental and paleoecological studies is hampered by the fact that Chironomus
larvae are difficult to identify to species because the larvae of many species
are morphologically similar. We used a combination of morphological, cytological
and genetic techniques to distinguish Chironomus larvae collected from 31 water
bodies located in eastern Canada, producing 17 distinguishable groupings. These
groups of larvae were ultimately identified as belonging to 14 known species (C.
anthracinus, C. bifurcatus, C. cucini, C. decorus-group sp. 2, C. dilutus, C.
entis, C. frommeri, C. harpi, C. maturus, C. nr. atroviridis (sp. 2i), C.
ochreatus, C. plumosus, C. staegeri and C. 'tigris') and three other species that
remain unidentified (C. sp. NAI-III). No single approach served to delimit and
identify larvae of all 17 Chironomus species that we collected. Although we
expected that morphological criteria alone would be insufficient, our results
suggest that DNA barcoding, using either the mitochondrial cox1 or the nuclear
gb2beta gene, was also inadequate for separating some Chironomus species. Thus we
suggest that multiple approaches will often be needed to correctly identify
Chironomus larvae to species.
PMID- 25113004
TI - Description of larvae of two closely related species Cassida palaestina Reiche,
1858 and Cassida rubiginosa Muller, 1776 (Coleoptera: Chrysomelidae: Cassidinae).
AB - Larvae of two closely related species Cassida palaestina Reiche, 1858 and Cassida
rubiginosa Muller, 1776 are described in detail including SEM microstructures.
First instars are extremely similar with no clear diagnostic characters, larvae
of Cassida palaestina are slightly more contrastingly coloured than larvae of C.
rubiginosa, the latter having darker scoli, basal part of supra-anal processes
and legs. Last instars differ in very subtle but constant characters: lateral
scoli of C. palaestina are slightly shorter than those of C. rubiginosa, in C.
palaestina tops of the lateral branches are armed apically with an elongate
cauliflower-shaped sensillum while in C. rubiginosa tops of the lateral branches
are more often armed with a pointed seta than with an elongate cauliflower-shaped
sensillum, and cauliflower-shaped sensilla on tergites are less elongate in C.
palaestina than in C. rubiginosa. These differences accompanied by distinguishing
characters of adults and their distribution range indicate that both taxa are
probably vicariant species with partial parapatric occurrence. Centaurea behen is
a new host plant for C. palaestina.
PMID- 25113005
TI - Review of the genus Hemistola Warren, 1893 in Taiwan with notes on an unusual
conifer-feeding larva and descriptions of three new species (Lepidoptera,
Geometridae, Geometrinae).
AB - The genus Hemistola Warren, 1893 in Taiwan is reviewed. Seven species are
confirmed, with descriptions of three new species provided: H. piceacola sp.
nov., H. fui sp. nov. and H. taiwanensis sp. nov. The immature stages and unusual
conifer-feeding behavior of H. piceacola on Taiwan spruce (Picea morrisonicola)
are reported. The distribution of H. tenuilinea (Alpheraky, 1897) is discussed
and this species is omitted from the Taiwanese fauna.
PMID- 25113006
TI - Review of the genus Anasta Emeljanov (Hemiptera: Dictyopharidae: Hastini) from
the Australasian region.
AB - The dictyopharid planthopper genus Anasta Emeljanov from the Australasian region
is revised to include six species including a new one: A. australiaca (Lallemand,
1935) comb. nov. (North Australia), A. lobosa sp. nov. (Papua New Guinea), A.
minuta (Lallemand, 1935) comb. nov. (Timor, Indonesia), A. prognatha (Distant,
1906) (North Australia, Papua New Guinea), A. timorina (Lallemand, 1935) (Timor,
Indonesia), and A. vitiensis Emeljanov et Wilson, 2009 (Fiji). Descriptions or
redescriptions of A. australiaca, A. lobosa sp. nov., and A. prognatha are
provided together with dorsal habitus and structural illustrations of male
genitalia. A key to the species of the genus and distribution map are provided.
The biogeography of the genus is discussed.
PMID- 25113008
TI - Mooreonuphis vespa, a new brooding species of Onuphidae (Annelida) from northern
Spain (Bay of Biscay).
AB - A new species of the genus Mooreonuphis Fauchald, 1982 collected from the
Cantabrian shelf (Bay of Biscay) is described. Mooreonuphis vespa sp. nov.
constitutes the first record of this genus in European waters and is
characterised by: conspicuous dark brown transverse segmental pigment bands;
antennae and palps with 3-5 basal ceratophoral rings and a very long distal ring;
unusually long and slender peristomial and dorsal cirri; simple branchiae from
chaetiger 17-19. We present observations on its reproductive biology (including
brooding behaviour) and remark on the biogeography of the genus.
PMID- 25113007
TI - A molecular phylogeny recovers Strabomantis aramunha Cassimiro, Verdade and
Rodrigues, 2008 and Haddadus binotatus (Spix, 1824) (Anura: Terrarana) as sister
taxa.
AB - The taxonomic and biogeographic affinities of Strabomantis aramunha from the
Campos Rupestres of Brazil are intriguing. A unique skull morphology of females
suggest affinities with the broad-headed eleutherodactylines of Northwestern
South America in the genus Strabomantis. Male and juvenile morphology nonetheless
suggest S. aramunha could be related to members of the recently described genus
Haddadus from eastern Brazil. We assess the affinities of S. aramunha using
molecular phylogenetic analyses of mitochondrial (12S, tRNAval, 16S, cyt b) and
nuclear sequences (RAG-1and rhodopsin). Bayesian inference, likelihood, and
parsimony analysis recover a highly supported clade with S. aramunha and H.
binotatus as sister taxa. Accordingly, we transfer S. aramunha to Haddadus, and
provide a new generic definition of the later. The distribution of species in
Haddadus (highlands of the Espinhaco mountain Range and coastal eastern Brazil)
is now concordant with the general pattern observed for other species in the
area.
PMID- 25113009
TI - Eviota santanai, a new Dwarfgoby from Timor-Leste (Teleostei: Gobiidae).
AB - Eviota santanai is described based on four specimens from Timor-Leste, taken in 5
8 m depth. In general coloration pattern, the species is most similar to E.
latifasciata, but differs in the cephalic sensory-pore system pattern, the
absence of an occipital spot, and live color including pinkish-mauve bars. Eviota
santanai has a dorsal/anal fin-ray formula of 8/8, 5th pelvic-fin ray absent,
some lower pectoral-fin rays branched, and IT and PITO pores absent.
PMID- 25113010
TI - Ebola and other viral haemorrhagic fevers.
PMID- 25113011
TI - Correlation between the retroversion of the humeral head and the orientation of
the intertubercular sulcus: a CT scan anatomical study.
AB - PURPOSE: The purpose was to study the anatomy of the humeral head, more
specifically the retroversion of the humeral head and the orientation of the
intertubercular sulcus, using CT scan, and to make correlations between those two
entities of the proximal humerus. METHODS: Sixty dry adult humeri from an
osteological collection underwent CT scan from the proximal to the distal
extremity. The measurements obtained by CT-reformation were recorded by two
independent radiologists. We determined the humeral head axis, the
transepicondylar axis, the retroversion of the humeral head, and the orientation
of the intertubercular sulcus (ITS). Statistical analysis using SPSS determined
the Pearson correlation coefficient. RESULTS: The CT scan measurements were
similar to those in the literature, and thus allowed us to validate CT scan
assessment. Statistical analysis showed a significant reverse correlation [the
coefficient of correlation was -0.37 (p = 0.004)] between the retroversion of the
humeral head and the orientation of the intertubercular sulcus: the more the
retroversion of the humeral head increases, the more the angle of the orientation
of the ITS decreases. CONCLUSIONS: To the best of our knowledge, this reverse
correlation between the retroversion of the humeral head and the orientation of
the intertubercular sulcus has never been described. This new anatomical data
might be helpful for orthopedic surgery.
PMID- 25113012
TI - Is coxa valga a predictor for the severity of knee osteoarthritis? A cross
sectional study.
AB - PURPOSE: In the present study, we aimed to evaluate the affect of the variations
in hip anatomy and pelvic geometry on the severity of knee OA. METHODS:
Idiopathic knee OA patients fulfilling the clinical criteria of American College
of Rheumatology for OA were enrolled in the study. Several measurements regarding
the hip and pelvis were performed on pelvic radiographs. Each knee was graded
according to the Kellgren and Lawrence (KL) radiographic system (0-4) along with
a categorization in accordance with the medial tibiofemoral joint space widths
(JSW). RESULTS: The study group consisted of 111 subjects. The inner and outer
pelvic diameters were getting wider as the JSW grade increased. Likewise, among
the hip measurements, femoral head, neck and shaft diameters and hip axis lengths
were linked with KL grade. There were significant differences in neck-shaft angle
(NSA) between groups of JSW with a highest NSA in JSW grade 3. The optimal cut
off value for NSA in predicting the severity of knee OA was 134.4 degrees .
Furthermore, NSA beyond 134.4 degrees was found to increase the risk of severe
knee OA eightfold. CONCLUSIONS: Variations in pelvic geometry and hip anatomy are
associated with the severity of knee OA. People with NSA of above 134.4 degrees
have eightfold increased risk of developing severe knee OA. Pelvic radiographies
could be evaluated at younger ages-particularly in people with high genetic
predispositions-to identify the individuals at high risk and in turn, to tailor
the preventive measures to these subjects.
PMID- 25113013
TI - Purification and characterization of a novel alkaline beta-1,3-1,4-glucanase
(lichenase) from thermophilic fungus Malbranchea cinnamomea.
AB - A novel alkaline beta-1,3-1,4-glucanase (McLic1) from a thermophilic fungus,
Malbranchea cinnamomea, was purified and biochemically characterized. McLic1 was
purified to homogeneity with a purification fold of 3.1 and a recovery yield of
3.7 %. The purified enzyme was most active at pH 10.0 and 55 degrees C, and
exhibited a wide range of pH stability (pH 4.0-10.0). McLic1 displayed strict
substrate specificity for barley beta-glucan, oat beta-glucan and lichenan, but
did not show activity towards other tested polysaccharides and synthetic p
nitrophenyl derivates, suggesting that it is a specific beta-1,3-1,4-glucanase.
The K m values for barley beta-glucan, oat beta-glucan and lichenan were
determined to be 0.69, 1.11 and 0.63 mg mL(-1), respectively. Moreover, the
enzyme was stable in various non ionic surfactants, oxidizing agents and several
commercial detergents. Thus, the alkaline beta-1,3-1,4-glucanase may have
potential in industrial applications, such as detergent, paper and pulp
industries.
PMID- 25113014
TI - Metal-free hydrogenation catalyzed by an air-stable borane: use of solvent as a
frustrated Lewis base.
AB - In recent years 'frustrated Lewis pairs' (FLPs) have been shown to be effective
metal-free catalysts for the hydrogenation of many unsaturated substrates. Even
so, limited functional-group tolerance restricts the range of solvents in which
FLP-mediated reactions can be performed, with all FLP-mediated hydrogenations
reported to date carried out in non-donor hydrocarbon or chlorinated solvents.
Herein we report that the bulky Lewis acids B(C6Cl5)x(C6F5)(3-x) (x=0-3) are
capable of heterolytic H2 activation in the strong-donor solvent THF, in the
absence of any additional Lewis base. This allows metal-free catalytic
hydrogenations to be performed in donor solvent media under mild conditions;
these systems are particularly effective for the hydrogenation of weakly basic
substrates, including the first examples of metal-free catalytic hydrogenation of
furan heterocycles. The air-stability of the most effective borane,
B(C6Cl5)(C6F5)2, makes this a practically simple reaction method.
PMID- 25113015
TI - Partial proportional odds model-an alternate choice for analyzing pedestrian
crash injury severities.
AB - The conventional methods for crash injury severity analyses include either
treating the severity data as ordered (e.g. ordered logit/probit models) or non
ordered (e.g. multinomial models). The ordered models require the data to meet
proportional odds assumption, according to which the predictors can only have the
same effect on different levels of the dependent variable, which is often not the
case with crash injury severities. On the other hand, non-ordered analyses
completely ignore the inherent hierarchical nature of crash injury severities.
Therefore, treating the crash severity data as either ordered or non-ordered
results in violating some of the key principles. To address these concerns, this
paper explores the application of a partial proportional odds (PPO) model to
bridge the gap between ordered and non-ordered severity modeling frameworks. The
PPO model allows the covariates that meet the proportional odds assumption to
affect different crash severity levels with the same magnitude; whereas the
covariates that do not meet the proportional odds assumption can have different
effects on different severity levels. This study is based on a five-year (2008
2012) national pedestrian safety dataset for Switzerland. A comparison between
the application of PPO models, ordered logit models, and multinomial logit models
for pedestrian injury severity evaluation is also included here. The study shows
that PPO models outperform the other models considered based on different
evaluation criteria. Hence, it is a viable method for analyzing pedestrian crash
injury severities.
PMID- 25113016
TI - Delayed presentation of cerebellar and spinal cord infarction as a complication
of computed tomography-guided transthoracic lung biopsy: a case report.
AB - INTRODUCTION: Computed tomography-guided transthoracic needle biopsy is a common
diagnostic procedure that is associated with various complications including
pneumothorax, parenchymal hemorrhage, and hemoptysis. A systemic air embolism is
a very rare (0.06 to 0.21%) but potentially fatal complication. CASE
PRESENTATION: A 70-year-old Korean male was admitted to our hospital for
evaluation of a solitary pulmonary nodule located adjacent to the right inferior
pulmonary vein in the medial basal segment of the right lower lobe. A computed
tomography-guided needle biopsy was performed by a radiologist using a coaxial
needle. A computed tomography image obtained immediately after the biopsy showed
intraluminal free air in the proximal ascending aorta. He complained of a mild
electrical current sensation in both lower extremities. After three hours he
complained of neurological deficit in both lower extremities as well as voiding
difficulty. The brain and spine magnetic resonance images showed a right
cerebellar and spinal cord infarction at the T8-10 levels. CONCLUSIONS: We report
a case of air embolism to the cerebellum and spinal cord causing infarction
presenting with an initial symptom of mild electrical current sensation in both
lower extremities during the transthoracic needle biopsy. For this potentially
fatal complication, early recognition, followed by prompt therapy is critical to
reducing morbidity and mortality.
PMID- 25113018
TI - A simple formula for quick and accurate calculation of maximum allowable volume
of local anaesthetic agents.
PMID- 25113017
TI - Is there any role for community involvement in the community-based health
planning and services skilled delivery program in rural Ghana?
AB - BACKGROUND: In Ghana, between 1,400 and 3,900 women and girls die annually due to
pregnancy related complications and an estimated two-thirds of these deaths occur
in late pregnancy through to 48 hours after delivery. The Ghana Health Service
piloted a strategy that involved training Community Health Officers (CHOs) as
midwives to address the gap in skilled attendance in rural Upper East Region
(UER). CHO-midwives collaborated with community members to provide skilled
delivery services in rural areas. This paper presents findings from a study
designed to assess the extent to which community residents and leaders
participated in the skilled delivery program and the specific roles they played
in its implementation and effectiveness. METHODS: We employed an intrinsic case
study design with a qualitative methodology. We conducted 29 in-depth interviews
with health professionals and community stakeholders. We used a random sampling
technique to select the CHO-midwives in three Community-based Health Planning and
Services (CHPS) zones for the interviews and a purposive sampling technique to
identify and interview District Directors of Health Services from the three
districts, the Regional Coordinator of the CHPS program and community
stakeholders. RESULTS: Community members play a significant role in promoting
skilled delivery care in CHPS zones in Ghana. We found that community health
volunteers and traditional birth attendants (TBAs) helped to provide health
education on skilled delivery care, and they also referred or accompanied their
clients for skilled attendants at birth. The political authorities, traditional
leaders, and community members provide resources to promote the skilled delivery
program. Both volunteers and TBAs are given financial and non-financial
incentives for referring their clients for skilled delivery. However, inadequate
transportation, infrequent supply of drugs, attitude of nurses remains as
challenges, hindering women accessing maternity services in rural areas.
CONCLUSIONS: Mutual collaboration and engagement is possible between health
professionals and community members for the skilled delivery program. Community
leaders, traditional and political leaders, volunteers, and TBAs have all been
instrumental to the success of the CHPS program in the UER, each in their unique
way. However, there are problems confronting the program and we have provided
recommendations to address these challenges.
PMID- 25113019
TI - Proof of concept trial on changes in current perception threshold after sacral
neuromodulation.
AB - OBJECTIVES: Sacral neuromodulation (SNM) is theorized to alter the neural
pathways that mediate bladder and urethral sensation. We hypothesize that SNM
affects current perception thresholds (CPTs) of afferent sensory nerve pathways.
MATERIALS AND METHODS: Eight women were enrolled and completed pre and
postoperative testing. A CPT device was used to measure CPT at 5 Hz (C-fibers),
250 Hz (Adelta-fibers), and 2000 Hz (Abeta-fibers) on the urethra and bladder
prior to and one month after SNM. Index finger readings at 2000 Hz served as
controls. RESULTS: SNM had the greatest effect on the bladder at 250 and 2000 Hz,
suggesting reduced bladder sensitivity. Significant changes in CPT were seen in
the bladder at 2000 Hz with a decrease in sensitivity (p = 0.033). CPT testing
was well tolerated, and no adverse events were identified. CONCLUSIONS: With a
measurable change in CPT values for Adelta-fibers and Abeta-fibers, these
findings suggest that SNM modulates large myelinated afferent fibers in the
bladder. Notably, little or no changes were found in the C-fiber CPT
measurements. More research is needed with a larger sample size to determine the
significance of these findings.
PMID- 25113020
TI - Temporal dynamics of eye movements are related to differences in scene complexity
and clutter.
AB - Recent research has begun to explore not just the spatial distribution of eye
fixations but also the temporal dynamics of how we look at the world. In this
investigation, we assess how scene characteristics contribute to these fixation
dynamics. In a free-viewing task, participants viewed three scene types: fractal,
landscape, and social scenes. We used a relatively new method, recurrence
quantification analysis (RQA), to quantify eye movement dynamics. RQA revealed
that eye movement dynamics were dependent on the scene type viewed. To understand
the underlying cause for these differences we applied a technique known as
fractal analysis and discovered that complexity and clutter are two scene
characteristics that affect fixation dynamics, but only in scenes with meaningful
content. Critically, scene primitives-revealed by saliency analysis-had no impact
on performance. In addition, we explored how RQA differs from the first half of
the trial to the second half, as well as the potential to investigate the
precision of fixation targeting by changing RQA radius values. Collectively, our
results suggest that eye movement dynamics result from top-down viewing
strategies that vary according to the meaning of a scene and its associated
visual complexity and clutter.
PMID- 25113021
TI - The role of color in expert object recognition.
AB - In the current study, we examined how color knowledge in a domain of expertise
influences the accuracy and speed of object recognition. In Experiment 1, expert
bird-watchers and novice participants categorized common birds (e.g., robin,
sparrow, cardinal) at the family level of abstraction. The bird images were shown
in their natural congruent color, nonnatural incongruent color, and gray scale.
The main finding was that color affected the performance of bird experts and bird
novices, albeit in different ways. Although both experts and novices relied on
color to recognize birds at the family level, analysis of the response time
distribution revealed that color facilitated expert performance in the fastest
and slowest trials whereas color only helped the novices in the slower trials. In
Experiment 2, expert bird-watchers were asked to categorize congruent color,
incongruent color, and gray scale images of birds at the more subordinate,
species level (e.g., Nashville warbler, Wilson's warbler). The performance of
experts was better with congruent color images than with incongruent color and
gray scale images. As in Experiment 1, analysis of the response time distribution
showed that the color effect was present in the fastest trials and was sustained
through the slowest trials. Collectively, the findings show that experts have
ready access to color knowledge that facilitates their fast and accurate
identification at the family and species level of recognition.
PMID- 25113023
TI - Pre-hospital care: a critical phase of the acute cardiovascular care management
process.
PMID- 25113022
TI - A simple biophysically plausible model for long time constants in single neurons.
AB - Recent work in computational neuroscience and cognitive psychology suggests that
a set of cells that decay exponentially could be used to support memory for the
time at which events took place. Analytically and through simulations on a
biophysical model of an individual neuron, we demonstrate that exponentially
decaying firing with a range of time constants up to minutes could be implemented
using a simple combination of well-known neural mechanisms. In particular, we
consider firing supported by calcium-controlled cation current. When the amount
of calcium leaving the cell during an interspike interval is larger than the
calcium influx during a spike, the overall decay in calcium concentration can be
exponential, resulting in exponential decay of the firing rate. The time constant
of the decay can be several orders of magnitude larger than the time constant of
calcium clearance, and it could be controlled externally via a variety of
biologically plausible ways. The ability to flexibly and rapidly control time
constants could enable working memory of temporal history to be generalized to
other variables in computing spatial and ordinal representations.
PMID- 25113026
TI - Social solidarity and the right to health: essential elements for people-centred
health systems.
PMID- 25113025
TI - "It's Not that Easy"--Medical Students' Fears and Barriers in End-of-Life
Communication.
AB - This study aims to assess and improve communication education for medical
students in palliative care (PC) with the use of simulated patients (SP) in
Germany. More specifically, to explore how students evaluate the use of SP for
end-of-life communication training and which fears and barriers arise. A pilot
course was implemented. Qualitative content analysis was used to analyse
transcribed recordings of the course. Pre- and post-course questionnaires
containing open-ended questions ascertained students' motivation for
participating, their preparation within their degree programme and whether they
felt they had learned something important within the course. Seventeen medical
students in their third to fourth year of education (age 22-31) participated in
the five-session course and answered the questionnaires (pre n = 17, post n =
12). Students felt insufficiently prepared and insecure. Discussing end-of-life
issues was experienced as challenging and emotionally moving. Within the
conversations, although students sometimes showed blocking behaviour in reaction
to emotional impact, they valued the consideration of emotional aspects as very
important. The course was overall highly appreciated and valued as being helpful.
The communication situation with the SP was perceived as authentic. Ten out of 12
students confirmed to have learned something important (post course). Our results
indicate an urgent need for better communication training for medical students.
Due to the fact that bedside teaching in PC is not feasible for all students,
training with standardized SP can be a way to generate an authentic learning
situation. Techniques to address fears and blocking behaviour should, however,
also be considered.
PMID- 25113024
TI - ABC inference of multi-population divergence with admixture from unphased
population genomic data.
AB - Rapidly developing sequencing technologies and declining costs have made it
possible to collect genome-scale data from population-level samples in nonmodel
systems. Inferential tools for historical demography given these data sets are,
at present, underdeveloped. In particular, approximate Bayesian computation (ABC)
has yet to be widely embraced by researchers generating these data. Here, we
demonstrate the promise of ABC for analysis of the large data sets that are now
attainable from nonmodel taxa through current genomic sequencing technologies. We
develop and test an ABC framework for model selection and parameter estimation,
given histories of three-population divergence with admixture. We then explore
different sampling regimes to illustrate how sampling more loci, longer loci or
more individuals affects the quality of model selection and parameter estimation
in this ABC framework. Our results show that inferences improved substantially
with increases in the number and/or length of sequenced loci, while less benefit
was gained by sampling large numbers of individuals. Optimal sampling strategies
given our inferential models included at least 2000 loci, each approximately 2 kb
in length, sampled from five diploid individuals per population, although
specific strategies are model and question dependent. We tested our ABC approach
through simulation-based cross-validations and illustrate its application using
previously analysed data from the oak gall wasp, Biorhiza pallida.
PMID- 25113027
TI - Economic cost of primary prevention of cardiovascular diseases in Tanzania.
AB - Tanzania is facing a double burden of disease, with non-communicable diseases
being an increasingly important contributor. Evidence-based preventive measures
are important to limit the growing financial burden. This article aims to
estimate the cost of providing medical primary prevention interventions for
cardiovascular disease (CVD) among at-risk patients, reflecting actual resource
use and if the World Health Organization (WHO)'s CVD medical preventive
guidelines are implemented in Tanzania. In addition, we estimate and explore the
cost to patients of receiving these services. Cost data were collected in four
health facilities located in both urban and rural settings. Providers' costs were
identified and measured using ingredients approach to costing and resource
valuation followed the opportunity cost method. Unit costs were estimated using
activity-based and step-down costing methodologies. The patient costs were
obtained through a structured questionnaire. The unit cost of providing CVD
medical primary prevention services ranged from US$30-41 to US$52-71 per patient
per year at the health centre and hospital levels, respectively. Employing the
WHO's absolute risk approach guidelines will substantially increase these costs.
The annual patient cost of receiving these services as currently practised was
estimated to be US$118 and US$127 for urban and rural patients, respectively.
Providers' costs were estimated from two main viewpoints: 'what is', that is the
current practice, and 'what if', reflecting a WHO guidelines scenario. The higher
cost of implementing the WHO guidelines suggests the need for further evaluation
of whether these added costs are reasonable relative to the added benefits. We
also found considerably higher patient costs, implying that distributive and
equity implications of access to care require more consideration. Facility
location surfaced as the main explanatory variable for both direct and indirect
patient costs in the regression analysis; further research on the influence of
other provider characteristics on these costs is important.
PMID- 25113028
TI - An assessment of individual-level factors associated with alcohol treatment
utilization among Mexican Americans.
AB - The purpose of this study is to identify enabling factors for treatment
utilization for alcohol-related problems, and to evaluate how enabling factors
vary by need for treatment, among two samples of Mexican American adults. These
two distinct samples included 2,595 current and former drinkers (one sample
included 787 U.S./Mexico border residents; the other sample included 740 Mexican
Americans living in U.S. cities not proximal to the border). Need for treatment
(alcohol disorder severity) and (male) gender were the primary correlates of
treatment utilization; and there was no moderation in the enabling factors by
need for treatment as "enablers" of utilization. Further theoretical and
empirical research is necessary to determine which mechanisms are driving
disparities in treatment utilization across racial/ethnic groups generally, and
Hispanic national groups specifically.
PMID- 25113029
TI - Sac1-Vps74 structure reveals a mechanism to terminate phosphoinositide signaling
in the Golgi apparatus.
AB - Sac1 is a phosphoinositide phosphatase of the endoplasmic reticulum and Golgi
apparatus that controls organelle membrane composition principally via regulation
of phosphatidylinositol 4-phosphate signaling. We present a characterization of
the structure of the N-terminal portion of yeast Sac1, containing the conserved
Sac1 homology domain, in complex with Vps74, a phosphatidylinositol 4-kinase
effector and the orthologue of human GOLPH3. The interface involves the N
terminal subdomain of the Sac1 homology domain, within which mutations in the
related Sac3/Fig4 phosphatase have been linked to Charcot-Marie-Tooth disorder
CMT4J and amyotrophic lateral sclerosis. Disruption of the Sac1-Vps74 interface
results in a broader distribution of phosphatidylinositol 4-phosphate within the
Golgi apparatus and failure to maintain residence of a medial Golgi
mannosyltransferase. The analysis prompts a revision of the membrane-docking
mechanism for GOLPH3 family proteins and reveals how an effector of
phosphoinositide signaling serves a dual function in signal termination.
PMID- 25113030
TI - The nebulin repeat protein Lasp regulates I-band architecture and filament
spacing in myofibrils.
AB - Mutations in nebulin, a giant muscle protein with 185 actin-binding nebulin
repeats, are the major cause of nemaline myopathy in humans. Nebulin sets actin
thin filament length in sarcomeres, potentially by stabilizing thin filaments in
the I-band, where nebulin and thin filaments coalign. However, the precise role
of nebulin in setting thin filament length and its other functions in regulating
power output are unknown. Here, we show that Lasp, the only member of the nebulin
family in Drosophila melanogaster, acts at two distinct sites in the sarcomere
and controls thin filament length with just two nebulin repeats. We found that
Lasp localizes to the Z-disc edges to control I-band architecture and also
localizes at the A-band, where it interacts with both actin and myosin to set
proper filament spacing. Furthermore, introducing a single amino acid change into
the two nebulin repeats of Lasp demonstrated different roles for each domain and
established Lasp as a suitable system for studying nebulin repeat function.
PMID- 25113032
TI - Full-length KIR3DL1*022 detected in an African donor.
AB - KIR3DL1*022 is significantly different from the most common West African allele -
KIR3DL1*01501.
PMID- 25113033
TI - Pirfenidone for the treatment of idiopathic pulmonary fibrosis.
AB - Pirfenidone is an orally administered drug with anti-fibrotic, anti-inflammatory
and anti-oxidant properties. The efficacy of pirfenidone is supported by a number
of Phase III trials as well as a Cochrane meta-analysis and tolerability data are
also provided by clinical trials and a long-term extension phase of these
studies. These trials led to the approval of pirfenidone for the treatment of
idiopathic pulmonary fibrosis (IPF) in Japan in 2008 and in Europe in 2011 and it
is now indicated for treatment of patients with mild-to-moderate IPF. The primary
endpoint of these studies has usually been the change in percentage predicted
forced vital capacity from baseline; there has been no improvement in respiratory
symptoms and/or quality of life measurements and/or decrease in mortality.
Clinical and basic research studies are needed to expand our knowledge,
understanding the final role of pirfenidone in the treatment of IPF and also
identifing genetic factors that influence the effectiveness of this treatment.
PMID- 25113034
TI - Citation analysis of the most- and least-cited articles in Clinical and
Experimental Ophthalmology: 2000-2013.
PMID- 25113035
TI - Ethical concerns of visiting nurses caring for older people in the community.
AB - BACKGROUND: An understanding of the ethical concerns encountered by visiting
nurses in the community is needed. Yet, there is a lack of research on this
topic. OBJECTIVES: The purpose of this study was to explore the ethical concerns
that visiting nurses experience when caring for vulnerable older people living in
a community. DESIGN AND SAMPLE: A qualitative thematic analysis was used to
explore the nature of the ethical issues experienced by visiting nurses (N = 13)
who care for vulnerable older people, over 65 years of age, in a South Korean
community. METHODS: In-depth interviews were conducted with visiting nurses.
Qualitative thematic analysis was used to explore the main themes of the
phenomenon. ETHICAL CONSIDERATIONS: This study was approved by the Institutional
Review Board of Chung-Ang University Bioethics Committee in South Korea. RESULTS:
Four ethical themes emerged from the qualitative data: (a) quantitative
performance rather than quality care, (b) clients being invisible, (c) tuning the
level of the relationship with clients, and (d) facing the visiting nurses' own
limitations. CONCLUSION: This study provides a theoretical basis to understand
the ethical aspects of visiting nurses' interactions with clients, which should
facilitate the development of ethical guidelines for visiting nurses to use in
making ethical decisions in their practice.
PMID- 25113036
TI - Is the hoopla over CPAF justified?
PMID- 25113031
TI - Phosphorylated RPA recruits PALB2 to stalled DNA replication forks to facilitate
fork recovery.
AB - Phosphorylation of replication protein A (RPA) by Cdk2 and the checkpoint kinase
ATR (ATM and Rad3 related) during replication fork stalling stabilizes the
replisome, but how these modifications safeguard the fork is not understood. To
address this question, we used single-molecule fiber analysis in cells expressing
a phosphorylation-defective RPA2 subunit or lacking phosphatase activity toward
RPA2. Deregulation of RPA phosphorylation reduced synthesis at forks both during
replication stress and recovery from stress. The ability of phosphorylated RPA to
stimulate fork recovery is mediated through the PALB2 tumor suppressor protein.
RPA phosphorylation increased localization of PALB2 and BRCA2 to RPA-bound
nuclear foci in cells experiencing replication stress. Phosphorylated RPA also
stimulated recruitment of PALB2 to single-strand deoxyribonucleic acid (DNA) in a
cell-free system. Expression of mutant RPA2 or loss of PALB2 expression led to
significant DNA damage after replication stress, a defect accentuated by poly-ADP
(adenosine diphosphate) ribose polymerase inhibitors. These data demonstrate that
phosphorylated RPA recruits repair factors to stalled forks, thereby enhancing
fork integrity during replication stress.
PMID- 25113037
TI - Desmoplastic fibroma of the mandible: a series of three cases and review of
literature.
AB - The desmoplastic fibroma (DF) is a rare, fibroblastic lesion of bone that
histologically resembles the desmoid tumor of soft tissue. Although classified as
benign, it frequently demonstrates aggressive behavior, often causing tooth
mobility, extensive bone destruction, and has a moderate to high recurrence rate.
We present three cases of DF in the mandible: the first in a 13 year old female
involving the mandibular body in the region of teeth #s 27-#28, the second in a
57 year old female with a lesion apical to tooth #30, and the third in a 20-year
old female involving the left posterior mandible. Clinical, histologic,
immunohistochemical (IHC) and radiographic features of this rare neoplasm are
discussed. The challenges encountered in establishing an accurate diagnosis due
to significant microscopic overlap with other spindle cell lesions are also
detailed. Additionally, the findings of IHC stains including vimentin, smooth
muscle actin, S-100 protein, beta-catenin, HHF-35 and proliferation marker, Ki-67
on 3 cases are reported. The potential for misdiagnosis is high, especially in
early lesions, since immunohistochemistry has been reported in literature to be
inconsistent when differentiating DFs from other spindle cell lesions. A
comparative review of DF and similar entities in the jaws with current
considerations in treatment and prognosis is presented.
PMID- 25113038
TI - Dermoid cyst of the parotid gland: report of a rare entity with literature
review.
AB - Dermoid cysts (DCs)are benign lesions and histologically composed of tissues
originating from ectoderm and mesoderm, but not endoderm. Approximately 7 % of
all DCs are seen in head and neck area. However, parotid gland is an extremely
rare localization in which DCs develop, and only 17 cases have been reported in
the literature to date. Correct preoperative diagnosis is difficult to be
established due to the rarity and ambiguous radiological findings. We report a
case of a 21-year old man. All previous reports reviewed and the pathogenesis as
well as the histopathologic and radiologic features are discussed.
PMID- 25113039
TI - The ratio of high-density lipoprotein cholesterol to apolipoprotein A-I predicts
myocardial injury following elective percutaneous coronary intervention.
AB - BACKGROUND: High-density lipoprotein (HDL) has cardioprotective properties. Each
HDL particle has a few molecules of apolipoprotein A-I (apoA-I) and carries
various amounts of cholesterol. The ratio of high-density lipoprotein cholesterol
(HDL-C) to apoA-I may reflect mean HDL particle size. HYPOTHESIS: HDL-C/apoA-I
ratio may provide more information than HDL-C and apoA-I in predicting myocardial
injury following elective percutaneous coronary intervention (PCI). METHODS: We
prospectively enrolled 2529 consecutive patients who underwent elective PCI and
assessed the relationships of preprocedural HDL-C, apoA-I, and their ratio with
peak cardiac troponin I (cTnI) within 24 hours after PCI. RESULTS: Neither HDL-C
nor apoA-I levels showed significant association with postprocedural cTnI
elevation, whereas HDL-C/apoA-I ratio was associated with postprocedural cTnI
elevation above 3 up to 30 * upper limit of normal (ULN), with the lowest risk in
the middle quintile (all P values for quadratic term were <0.05). Adjusted odds
ratios (95% confidence interval) of postprocedural cTnI >3 * ULN for quintile 1
to 5 of HDL-C/apoA-I ratio were: 1 (reference), 0.81 (0.62-1.07), 0.57 (0.43
0.75), 0.65 (0.49-0.85), and 0.76 (0.58-1.01), respectively, and the adjusted
odds ratios of postprocedural cTnI >30 * ULN for quintile 1 to 5 of HDL-C/apoA-I
ratio were: 1 (reference), 0.81 (0.49-1.361), 0.42 (0.23-0.77), 0.66 (0.38-1.14),
and 0.82 (0.49-1.38), respectively. CONCLUSIONS: There was a U-shaped association
between HDL-C/apoA-I ratio and myocardial injury following PCI.
PMID- 25113040
TI - Gastrogastric fistulae following gastric bypass surgery-clinical recognition and
treatment.
AB - Gastrogastric fistula (GGF) formation is an uncommon but well-recognized
complication following Roux-en-Y gastric bypass for morbid obesity. Patients with
GGF may be asymptomatic or have nonspecific problems of abdominal pain, weight
regain, or ulcer formation at the gastrojejunal anastomosis. Maintaining a high
index of suspicion is the key to diagnosis. Flexible upper endoscopy and upper
gastrointestinal fluoroscopy are complementary imaging modalities for securing
the diagnosis of GGF. Surgical repair of GGF is generally the most definitive
management but is invasive and has the potential for morbidity. Endoscopic
methods of closure have gained favor in recent years due to their noninvasive
nature despite the lack of long-term data regarding their success. Novel methods
of endoscopic closure, including endoscopic suturing, more closely resemble the
surgical paradigm and will likely supplant traditional surgical methods for the
management of GGF.
PMID- 25113041
TI - The role of endoscopy in the management of pancreatic necrosis.
AB - The management of acute pancreatitis has seen many advances over the past three
decades. Attempts to improve care have led to new definitions, classification
systems, and treatment strategies. Despite those efforts, considerable morbidity
and mortality result from complications of severe acute pancreatitis. Much
attention has been given to new ways to treat these complications, including
inflammatory pancreatic fluid collections and associated infections. Endoscopy
has become one of the established modalities for the treatment of these
complications in many expert centers. This chapter will specifically address the
role of endoscopy in the management of pancreatic necrosis.
PMID- 25113043
TI - Comparison of identification systems for psychrotrophic bacteria isolated from
raw bovine milk.
AB - Psychrotrophic bacteria in raw milk produce heat-resistant extracellular
proteases, resulting in spoilage and shelf-life reduction of ultrahigh
temperature treated milk and milk products. Controlling of these spoilage
microbes requires rapid and reliable identification systems for screening of raw
milk. This study aimed to compare commercial bacterial identification systems
with a genetic method (considered as the 'gold standard' method) for the
identification of heat-resistant protease producing bacteria in raw milk. Five
bacterial identification systems were compared based on typability,
discrimination power (i.e. Simpson's Index of Diversity), reproducibility and
speed of analysis. The accuracy of 16S rRNA gene sequencing, Biolog, MALDI-TOF
MS, API, and Microbact for the identification of Gram negative bacilli at the
species level was 100.0%, 86.8%, 63.2%, 60.5% and 57.9%, respectively. The Gram
positive bacilli were identified by 16S rRNA gene sequencing, Biolog, MALDI-TOF
MS, and API with accuracies at the species level of 100.0%, 85.0%, 95.0% and
90.0%, respectively. The 16S rRNA gene sequencing and phylogenetic analysis
discriminated Pseudomonas fluorescens, Pseudomonas syringae, Hafnia alvei,
Bacillus cereus, Bacillus pumilus and Bacillus licheniformis to the subspecies
level. The Simpson's Index of Diversity scores were 0.966, 0.711, 0.496, 0.472,
and 0.140, for 16S rRNA gene sequencing, Biolog, MALDI-TOF MS, API and Microbact,
respectively. Limited reference profiles in the databases of Biolog, MALDI-TOF
MS, API and Microbact systems reduced their accuracy in bacterial identification,
compared to 16S rRNA gene sequencing. The rapidity of each assay is in the
following order; MALDI-TOF MS>16S rRNA gene sequencing>Biolog>Microbact>API. The
reproducibility of the assays is in the order of 16S rRNA gene
sequencing>API>Microbact>MALDI-TOF MS>Biolog. Thus, 16S rRNA gene sequencing
appears to be the most reliable and robust system for the identification of dairy
spoilage bacteria. The Biolog system is suitable for the identification of Gram
negative spoilage bacteria, while MALDI-TOF MS and API systems are suitable for
the identification of Gram positive spoilage bacteria isolated from raw milk. The
commercial systems used in this study have been developed and extensively used
for the identification of clinical microbes but only a limited number of studies
used those systems to identify the environmental microorganisms that often
contaminate raw milk. Therefore, comparison of those systems for the
identification of spoilage microbes in raw milk would provide better
understanding of their suitability for routine dairy microbiology and more
extensive dairy research.
PMID- 25113042
TI - Chromoendoscopy for colorectal cancer surveillance in patients with inflammatory
bowel disease.
AB - Chromoendoscopy utilizes colorimetric techniques to increase detection of lesions
that are difficult to see or cannot be seen with conventional white light
endoscopy. Multiple studies have demonstrated that chromoendoscopy with dye
spraying significantly increases the detection of dysplastic lesions in patients
with chronic inflammatory bowel disease (IBD) of the colon undergoing
colonoscopy. Furthermore, chromoendoscopy may obviate the need for random
biopsies and pending additional studies and may allow increased intervals between
surveillance exams, reducing costs while increasing the sensitivity for detection
of dysplasia per exam. Despite convincing data supporting the use of
chromoendoscopy for IBD colonic surveillance, it is seldom utilized outside of
academic centers. Here, we review the current approach to colorectal cancer
surveillance in IBD focusing on the data supporting the use of chromoendoscopy
including its use in a community setting and offer practical recommendations for
incorporating chromoendoscopy as a routine part of surveillance in IBD regardless
of practice setting.
PMID- 25113044
TI - Characterization of integrons and resistance genes in multidrug-resistant
Salmonella enterica isolated from meat and dairy products in Egypt.
AB - Foodborne pathogens are a leading cause of illness and death, especially in
developing countries. The problem is exacerbated if bacteria attain multidrug
resistance. Little is currently known about the extent of antibiotic resistance
in foodborne pathogens and the molecular mechanisms underlying this resistance in
Africa. Therefore, the current study was carried out to characterize, at the
molecular level, the mechanism of multidrug resistance in Salmonella enterica
isolated from 1600 food samples (800 meat products and 800 dairy products)
collected from different street venders, butchers, retail markets and
slaughterhouses in Egypt. Forty-seven out of 69 isolates (68.1%) showed multidrug
resistance phenotypes to at least three classes of antimicrobials. The incidence
of multidrug-resistant isolates was higher in meat products (37, 69.8%) than in
dairy products (10, 62.5%). The multidrug-resistant serovars included, S.
enterica serovar Typhimurium (24 isolates, 34.8%), S. enterica serovar
Enteritidis, (15 isolates, 21.8%), S. enterica serovar Infantis (7 isolates,
10.1%) and S. enterica non-typable serovar (1 isolate, 1.4%). The highest
resistance was to ampicillin (95.7%), then to kanamycin (93.6%), spectinomycin
(93.6%), streptomycin (91.5%) and sulfamethoxazole/trimethoprim (91.5%). PCR and
DNA sequencing were used to screen and characterize integrons and antibiotic
resistance genes and 39.1% and 8.7% of isolates were positive for class 1 and
class 2 integrons, respectively. beta-lactamase-encoding genes were identified in
75.4% of isolates and plasmid-mediated quinolone resistance genes were identified
in 27.5% of isolates. Finally, the florphenicol resistance gene, floR, was
identified in 18.8% of isolates. PCR screening identified S. enterica serovar
Typhimurium DT104 in both meat and dairy products. This is the first study to
report many of these resistance genes in dairy products. This study highlights
the high incidence of multidrug-resistant S. enterica in meat and dairy products
in Egypt, with the possibility of their transfer to humans leading to therapeutic
failure. Therefore, the overuse of antibiotics in animals should be drastically
reduced in developing countries.
PMID- 25113045
TI - Biocontrol activity of four non- and low-fermenting yeast strains against
Aspergillus carbonarius and their ability to remove ochratoxin A from grape
juice.
AB - Aspergillus spp. infection of grape may lead to ochratoxin A (OTA) contamination
in processed beverages such as wine and grape juice. The aim of the current study
was to evaluate the biocontrol potential of two non-fermenting (Cyberlindnera
jadinii 273 and Candida friedrichii 778) and two low-fermenting (Candida
intermedia 235 and Lachancea thermotolerans 751) yeast strains against the
pathogenic fungus and OTA-producer Aspergillus carbonarius, and their ability to
remove OTA from grape juice. Two strains, 235 and 751, showed a significant
ability to inhibit A. carbonarius both on grape berries and in in vitro
experiments. Neither their filtrate nor their autoclaved filtrate culture broth
was able to prevent consistently pathogen growth. Volatile organic compounds
(VOCs) produced by all four selected yeasts were likely able to consistently
prevent pathogen sporulation in vitro. VOCs produced by the non-fermenting strain
778 also significantly reduced A. carbonarius vegetative growth. Three yeast
strains (235, 751, and 778) efficiently adsorbed artificially spiked OTA from
grape juice, while autoclaving treatment improved OTA adsorption capacity by all
the four tested strains. Biological control of A. carbonarius and OTA
decontamination using yeast is proposed as an approach to meet the Islamic
dietary laws concerning the absence of alcohol in halal beverages.
PMID- 25113046
TI - Synthesis and in vitro pharmacological evaluation of novel 2-hydroxypropyl-4
arylpiperazine derivatives as serotoninergic ligands.
AB - This paper reports the synthesis of new norbornene and exo-N-hydroxy-7
oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboximide derivatives and their binding to
the 5-HT1A , 5-HT2A , and 5-HT2C receptors, in order to identify selective
ligands for these 5-hydroxytryptamine (5-HT, serotonine) receptor subtypes. The
combination of structural elements (heterocyclic nucleus, hydroxyalkyl chain, and
4-substituted piperazine) known to be critical for affinity to 5-HT1A receptors
and the proper selection of substituents led to compounds with high specificity
and affinity toward serotoninergic receptors. The most active compounds were
selected and further evaluated for their binding affinities to D1 , D2
dopaminergic and alpha1 , alpha2 adrenergic receptors. 4-[3-[4-(2
Furoyl)piperazin-1-yl]propoxy-2-ol]-4-aza-tricyclo[5.2.1.02,6]dec-8-ene-3,5-dione
3e with Ki = 5.04 +/- 0.227 nM was the most active and selective derivative for
the 5-HT2C receptor with respect to other serotonin receptors, and the most
selective derivative versus dopaminergic and adrenergic receptors.
PMID- 25113047
TI - Interobserver and intraobserver repeatability of lipid layer pattern evaluation
by two experienced observers.
AB - PURPOSE: The lipid layer plays a major role in limiting evaporation of the tear
film. Based on interference phenomena, there is a test directed to lipid layer
pattern (LLP) evaluation, but is affected by subjective interpretation of the
patterns. The aim of this study is to compare the LLP evaluation between two
experienced observers on a group of healthy patients. Furthermore, observers re
evaluated the same images to check their individual repeatability. MATERIALS AND
METHODS: LLP was examined using a Tearscope-plus (Keeler, Windsor, UK) attached
to a slit lamp. Tear film was recorded by a Topcon DV-3 digital camera video and
LLP images were captured. This yielded 124 LLP images that were categorized
(based on Guillon's scheme) by two expert observers in two sessions separated by
one month. Interobserver repeatability and intraobserver repeatability between
both sessions were studied by using Cohen's kappa coefficient. RESULTS: Comparing
LLP categorization between both observers, Cohen's kappa coefficient was 0.615
and 0.633 for first and second session, respectively. When comparing LLP
categorization by the same observer between both sessions, Cohen's kappa
coefficient was 0.770 and 0.812 for Observer 1 and Observer 2, respectively.
These results indicate substantial correlation in all cases. The most frequent
misinterpretations were between open and closed meshwork and Wave and closed
meshwork patterns. CONCLUSION: Although substantial correlation was found between
categorizations of experienced observers, misinterpretation of the patterns may
appear even in the same observer. Some misinterpretations between adjacent
patterns could be palliated by including intermediate patterns between those
categories.
PMID- 25113048
TI - An imprinted Ag@CdS core shell nanoparticle based optical-electrochemical dual
probe for trace level recognition of ferritin.
AB - In this work, we present a new approach to prepare the Ag@CdS core-shell
fluorescent nanoparticles wrapped with molecularly imprinted polymer for ferritin
macromolecule by capping with vinyl derivative of cysteine. The imprinted Ag@CdS
nanoparticle was prepared via activator regenerated by electron transfer-atom
transfer radical polymerization (ARGET-ATRP) method onto the surface of vinyl
silane modified pencil graphite electrode. Combination of Ag and CdS in a single
motif causes the dual behavior of core shell nanoparticle, which shows enhanced
fluorescence as well as electrochemical properties. The performance of the
obtained imprinted sensor was investigated by cyclic voltammetry, electrochemical
impedance spectroscopy, chronocoulometry, differential pulse voltammetry and
fluorescence spectrophotometry. Under the optimal experimental conditions, the
current response of the electrochemical sensor was linear to ferritin
concentrations in the range from 1.99 to 23.43 ug L-1, with the detection limit
of 0.65 ug L-1. Similarly, a linear response was obtained between fluorescence
quenching of imprinted Ag@CdS and concentration of ferritin in the range from 4.0
to 91.0 ug L-1, with limit of detection (LOD) of 1.3 ug L-1. The method was
successfully applied to the analysis of blood serum samples of five different men
and women with acceptable recoveries of 99.7% and 100.3% (RSD in %=1.0-2.0).
PMID- 25113049
TI - An exonuclease I-based label-free fluorometric aptasensor for adenosine
triphosphate (ATP) detection with a wide concentration range.
AB - A novel aptamer-based label-free assay for sensitive and selective detection of
ATP was developed. This assay employs a new aptamer/fluorescent probe system that
shows resistance to exonuclease I (Exo I) digestion upon binding to ATP
molecules. In the absence of ATP, the complex between the ATP-binding aptamer
(ATP-aptamer) and a DNA binding dye, berberine, is digested upon the addition of
exonuclease I, leading to the release of berberine into solution and
consequently, quenched berberine fluorescence. In the presence of ATP, the ATP
binding aptamer folds into a G-quadruplex structure that is resistant to Exo I
digestion. Accordingly, berberine is protected in the G-quadruplex structure and
high fluorescence intensity is observed. As such, based on the fluorescence
signal change, a label-free fluorescence assay for ATP was developed. Factors
affecting the analysis of ATP including the concentration of ATP-binding aptamer,
reaction time, temperature and the concentration of Exo I were comprehensively
investigated. Under optimal conditions, the fluorescence intensity of the sensing
system displayed a response for ATP in a wide range up to 17.5 mM with a
detection limit of 140 nM.
PMID- 25113050
TI - Using poly(3-aminophenylboronic acid) thin film with binding-induced ion flux
blocking for amperometric detection of hemoglobin A1c.
AB - This study reports a novel enzyme-free, label-free amperometric method for direct
detection of hemoglobin A1c (Hb(A1c)), a potent biomarker for diabetes diagnosis
and prognosis. The method relies on an electrode modified with poly(3
aminophenylboronic acid) (PAPBA) nanoparticles (20-50 nm) and a sensing scheme
named "binding-induced ion flux blocking." The PAPBA nanoparticles were
characterized by FT-IR, XPS, TEM, and SEM. Being a polyaniline derivative, PAPBA
showed an ion-dependent redox behavior, in which insertion or extraction of ions
into or out of PABPA occurred for charge balance during the electron transfer
process. The polymer allowed Hb(A1c) selectively bound to its surface via forming
the cis-diol linkage between the boronic acid and sugar moieties. Voltammetric
analyses showed that Hb(A1c) binding decreased the redox current of PAPBA;
however, the binding did not alter the redox potentials and the apparent
diffusivities of ions. This suggests that the redox current of PAPBA decreased
due to an Hb(A1c) binding-induced ion flux blocking mechanism, which was then
verified and characterized through an in situ electrochemical quartz crystal
microbalance (EQCM) study. Assay with Hb(A1c) by differential pulse voltammetry
(DPV) indicates that the peak current of a PAPBA electrode has a linear
dependence on the logarithm of Hb(A1c) concentration ranging from 0.975 to 156
MUM. The Hb(A1c) assay also showed high selectivity against ascorbic acid,
dopamine, uric acid, glucose and bovine serum albumin. This study has
demonstrated a new method for developing an electrochemical Hb(A1c) biosensor and
can be extended to other label-free, indicator-free protein biosensors based on a
similar redox polymer electrode.
PMID- 25113051
TI - Synthesis of carbon nanotube-nickel nanocomposites using atomic layer deposition
for high-performance non-enzymatic glucose sensing.
AB - A useful strategy has been developed to fabricate carbon-nanotube-nickel (CNT-Ni)
nanocomposites through atomic layer deposition (ALD) of Ni and chemical vapor
deposition (CVD) of functionalized CNTs. Various techniques, including scanning
electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray
photoelectron spectroscopy (XPS), were used to characterize the morphology and
the structure of as-prepared samples. It was confirmed that the products possess
uniform Ni nanoparticles that are constructed by finely controlled deposition of
Ni onto oxygen or bromine functionalized CNT surface. Electrochemical studies
indicate that the CNT-Ni nanocomposites exhibit high electrocatalytic activity
for glucose oxidation in alkaline solutions, which enables the products to be
used in enzyme-free electrochemical sensors for glucose determination. It was
demonstrated that the CNT-Ni nanocomposite-based glucose biosensor offers a
variety of merits, such as a wide linear response window for glucose
concentrations of 5 MUM-2 mM, short response time (3 s), a low detection limit (2
MUM), high sensitivity (1384.1 MUA mM(-1) cm(-2)), and good selectivity and
repeatability.
PMID- 25113052
TI - A highly sensitive non-enzymatic glucose sensor based on bimetallic Cu-Ag
superstructures.
AB - Bimetallic Cu-Ag superstructures were successfully fabricated for the first time
by using the natural leaves as reducing agent through a facile one-step
hydrothermal process. Morphology, structure and composition of the Cu-Ag
superstructures were characterized by field emission scanning electron microscopy
(FESEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray
photoelectron spectra (XPS) and inductively coupled plasma-optical emission
spectroscopy (ICP-OES), respectively. The results reveal that the Cu-Ag
superstructure is bimetallic nanocomposite constructed by nanoparticles with low
Ag content and shows a rough surface and porous flexural algae-like
microstructure. By using a three-dimensional nickel foam as the scaffold, a novel
non-enzymatic glucose sensor based on Cu-Ag nanocomposites has been fabricated
and applied to non-enzymatic glucose detection. The as-prepared Cu-Ag
nanocomposites based glucose sensor displays distinctly enhanced electrocatalytic
activity compared to those obtained with pure Cu nanomaterials prepared with a
similar procedure, revealing a synergistic effect of the matrix Cu and the doped
Ag. Cyclic voltammetry, chronoamperometry and electrochemical impedance
spectroscopy indicate that the Cu-Ag superstructures based glucose sensor
displays a fascinating sensitivity up to 7745.7 MUA mM(-1) cm(-2), outstanding
detection limit of 0.08 MUM and fast amperometric response (<2 s) for glucose
detection. Furthermore, the sensor also exhibits significant selectivity,
excellent stability and reproducibility, as well as attractive feasibility for
real sample analysis. Because of its excellent electrochemical performance, low
cost and easy preparation, this novel electrode material is a promising candidate
in the development of non-enzymatic glucose sensor.
PMID- 25113054
TI - Temperament and character as determinants of well-being.
AB - OBJECTIVES: We aimed to evaluate the effects of Temperament and Character
Inventory (TCI) personality measures on well-being scores in a sample of 49-51
year old New Zealanders. Previous research has linked high self-directedness (SD)
and low harm avoidance (HA) with well-being. We hypothesised that SD and HA would
have predictive power for Warwick-Edinburgh Mental Well-being Scale (WEMWBS) well
being. We anticipated that character profiles with high SD and cooperativeness
(CO) would be associated with higher well-being scores while high self
transcendence (ST) scores would have less of an influence on well-being in a
secular population such as New Zealand. Additionally we aimed to describe and
assess the performance of a well-being measure, the WEMWBS and we intended to
clarify the factors that underlie the questionnaire. METHODS: A cohort of 404
randomly selected participants in a study of ageing had WEMWBS means calculated
and with principal component analysis used to investigate the factors that
underlie the WEMWBS. Multiple hierarchical regression was used to predict WEMWBS
scores from socio-demographic and TCI personality variables. ANOVA were used to
explore the non-linear effects of personality profiles on well-being. RESULTS:
Principal components analysis revealed one significant factor which explained
54.34% of the variance. After initial univariate analysis current depression,
marital status and standard of living were entered at the first step of the
multivariate regression. They explained 20% of the variance. In step two the
seven TCI personality variables were added to the model, explaining a total of
49% (R(2) change=0.29). Low HA, high SD and the absence of current depression
were the main predictors of WEMWBS scores. Character profiles featuring high SD
produced significantly higher scores on the WEMWBS. Total WEMWBS scores were
normally distributed, and the mean was 52.83 (95% CI 51.96-53.70). CONCLUSIONS:
The key determinants of well-being were absence of current depression and
personality variables, especially low HA and high SD. The WEMWBS has face
validity and the New Zealand results were very similar to the UK results.
PMID- 25113053
TI - Piezoresistive microcantilever-based DNA sensor for sensitive detection of
pathogenic Vibrio cholerae O1 in food sample.
AB - Pathogenic Vibrio cholerae produces a cholera toxin which is the cause of a
severe diarrheal disease called "Cholera". Available detection methods, including
standard bacteriological test and immuno-based detection, are specific to the
suspected pathogenic V. cholerae O1 and O139, but they are not specific to the
cholera toxin producible strain. This work combined the polymerase chain reaction
(PCR) of cholera toxin gene, ctxA gene, and microcantilever-based DNA sensor to
improve the sensitivity and specificity of detection. Gold coated
microcantilever, 250 um long and 50 um wide, with an embedded polysilicon wire
acting as a piezoresistive material was modified by a self-assembled monolayer
(SAM) of 3-mercaptopropionic acid (MPA) for immobilization of specific DNA probe
via avidin layer on the surface. The avidin and 5' biotinylated single-stranded
DNA (ssDNA) probe concentrations were optimized for the immobilization at 50
ug/mL and 1 uM, respectively. The hybridization between ssDNA probe on this DNA
sensor and target DNA creates nanomechanical bending and resistance change of
piezoresistive material inside the beam. This microcantilever-based DNA sensor
offers a detection sensitivity of 3.25 pg or 14 nM of DNA template for ctxA gene
detection. The lowest number of V. cholerae O1 in food sample with and without
the enrichment process that the polymerase chain reaction (PCR) for ctxA gene
combined with this DNA sensor can detect is 0.835 and 835 cells/g, respectively.
This detection sensitivity is 10 times higher than that of the conventional PCR
method.
PMID- 25113055
TI - Losing control: assaultive behavior as a predictor of impulse control disorders
in young adults.
AB - OBJECTIVE: Assaultive behaviors are common among young people and have been
associated with a range of other unhealthy, impulsive behaviors such as substance
use and problem gambling. This study sought to determine the predictive ability
of single assaultive incidents for impulse control disorders, an association that
has yet to be examined, especially in young adults. METHODS: The authors
conducted a university-wide email survey in the spring of 2011 on 6000 university
students. The survey examined assaultive behavior and associated mental health
variables (using a clinically validated screening instrument, the Minnesota
Impulsive Disorders Interview), stress and mood states, and psychosocial
functioning. RESULTS: The rate of response was 35.1% (n=2108). 109 (5.9%)
participants reported that they had assaulted another person or destroyed
property at some time in their lives. Compared with respondents without lifetime
assaultive behavior, those with a history of assaultive or destructive behavior
reported more depressive symptoms, more stress, and higher rates of a range of
impulse control disorders (intermittent explosive disorder, compulsive sexual
behavior, compulsive buying, and skin picking disorder). CONCLUSIONS: Assaultive
behavior appears fairly common among college students and is associated with
symptoms of depression and impulse control disorders. Significant distress and
diminished behavioral control suggest that assaultive behaviors may often be
associated with significant morbidity. Additional research is needed to develop
specific prevention and treatment strategies for young adults attending college
who report problems with assaultive behaviors.
PMID- 25113056
TI - A preliminary investigation of the long-term outcome of the Unified Protocol for
Transdiagnostic Treatment of Emotional Disorders.
AB - OBJECTIVE: The aim of this study is to conduct a preliminary examination of long
term outcomes on a broad range of affective disorder symptoms treated with a
newly developed intervention: The Unified Protocol for Transdiagnostic Treatment
of Emotional Disorders (UP). METHOD: Maintenance of treatment gains at long-term
follow-up (LTFU) were explored in patients (N=15, mean age=32.27; 60% female) who
completed a clinical trial of the UP. RESULTS: Treatment gains observed at 6
month follow-up (6MFU) on measures of clinical severity, general symptoms of
depression and anxiety, and a measure of symptom interference in daily
functioning were largely maintained 12months later (at an average of 18months
posttreatment), and any significant changes from 6MFU to LTFU reflected small
increases in symptoms that remained, on average, in the subclinical range.
CONCLUSIONS: These findings provide the first initial support for the durability
of broad treatment gains following transdiagnostic treatment.
PMID- 25113057
TI - Spread of carbapenemase-producing enterobacteria in a southwest hospital in
China.
AB - BACKGROUND: The rapid emergence and dissemination of carbapenem resistance in
Enterobacteriaceae complicates the treatment of infections caused by these
organisms. METHODS: We collected clinical isolates with meropenem inhibition
zones of <= 22 mm from January 1, 2009, through December 31, 2010. We attempted
to amplify the NDM-1 gene from these isolates and conducted the modified Hodge
test (MHT). The minimal inhibitory concentration (MIC) of the MHT-positive
strains was determined by the agar disk dilution method. The carbapenemase
encoding resistance genes of these strains were examined using polymerase chain
reaction (PCR) analysis and a sequencing strategy to characterize these enzymes.
The clonal relationship among isolates was analyzed by pulsed-field gel
electrophoresis (PFGE). RESULTS: Among the 158 Enterobacteriaceae isolates that
were collected, there were no NDM-1-positive strains and 26 MHT-positive strains.
Among the latter, 18 strains were IMP-4-positive, and 1 was KPC-2-positive. In
addition, 15 of the IMP-4-positive Klebsiella pneumoniae strains belonged to 4
PFGE genotypes, with 8 strains having the same genotype. CONCLUSION: These
results suggest that nosocomial infections are one of the main reasons for the
spread of these resistant strains.
PMID- 25113058
TI - Caspase-3 inhibition prevents the development of hepatopulmonary syndrome in
common bile duct ligation rats by alleviating pulmonary injury.
AB - BACKGROUND & AIMS: Common bile duct ligation (CBDL) rats is an accepted
experimental model of hepatopulmonary syndrome (HPS), defined as liver disease
and intrapulmonary vascular dilatation and hypoxaemia. Pulmonary Akt and ERK
activation followed by angiogenesis in the later stages of CBDL, contribute to
the pathogenesis of HPS. However, the mechanisms behind Akt and ERK activation
remain undefined. Pulmonary injury induced by increased bilirubin, endotoxin and
inflammatory mediators occurs in the early stages of CBDL. We assessed the
effects of relieving pulmonary injury on Akt and ERK activation and on the
development of HPS following CBDL. METHODS: Pulmonary injury, angiogenesis,
arterial oxygenation, cell proliferation and, phospho-Akt and ERK1 were evaluated
in CBDL animals with or without caspase-3 inhibition (Z-DEVD-FMK). Pulmonary
injury was assessed by histology and quantifying apoptosis and aquaporin-1 (AQP1)
levels. Lung angiogenesis was assessed by quantifying AQP1 level, vWF-positive
cells and microvessel count. RESULTS: Pulmonary apoptosis and caspase-3
activation were markedly increased in the early stages of CBDL. Caspase-3
inhibition alleviated apoptosis, the reduction in AQP1, phospho-Akt and ERK1
levels and pulmonary injury 1 week after CBDL. Caspase-3 inhibition also reduced
AQP1, phospho-Akt and ERK1 levels, vWF-positive cells, cell proliferation,
microvessel count, and microvascular dilatation and improved arterial oxygenation
3 weeks following CBDL. CONCLUSIONS: Caspase-3 inhibition alleviates pulmonary
injury, thereby preventing angiogenesis as well as the development of HPS in CBDL
rats. These effects are related to the regulation of the Akt and ERK1 pathways.
PMID- 25113060
TI - In vivo gastric detection of alpha-synuclein inclusions in Parkinson's disease.
AB - alpha-Synuclein inclusions have been identified in the brain and some parts of
the enteric nervous system in Parkinson's disease cases. We aimed to assess these
inclusions in gastric mucosa samples from patients with symptomatic Parkinson's
disease. Random biopsies were performed by gastroscopy in 28 patients with
Parkinson's disease and in 29 age- and sex-matched controls. Gastroscopy was
performed to start enteral levodopa (L-dopa) therapy in cases and for diagnostic
purposes in controls (gastroesophageal reflux, anemia, and abdominal pain were
the main indications). The clinical definition of cases and controls was made a
priori. Six controls had data suggestive of "mild presymptomatic parkinsonism".
Biopsy specimens were immunostained for alpha-synuclein. The neuropathological
diagnosis was established post hoc. No differences were found in the baseline
characteristics of the groups. Positive fibers for the alpha-synuclein protein
were observed in 17 of 28 (60.7%) Parkinson's disease patients, 1 of 23 controls
(4.3%), and 1 of 6 (16.7%) cases of incident "mild presymptomatic parkinsonism."
Neuropathological diagnosis based on alpha-synuclein immunostaining showed a
sensitivity of 85% (95% confidence interval [CI] 62.1-96.8), specificity of 95%
(95% CI 76.2-99.9) and area under the receiver operating characteristics curve
(AUC) of 0.90 (95% CI 0.80-1.00). No adverse events occurred. Detection of alpha
synuclein inclusions in the gastric mucosa is a useful and safe tool providing in
vivo evidence of the underlying neurodegenerative peripheral involvement linked
to Parkinson's disease. Further studies are warranted to determine its
pathophysiological implications.
PMID- 25113062
TI - Reactions of atomic hydrogen with formic acid and carbon monoxide in solid
parahydrogen II: Deuterated reaction studies.
AB - It is difficult to determine whether the measured rate constant for reaction of
atomic hydrogen with formic acid reported in Part 1 reflects the H atom quantum
diffusion rate or the rate constant for the tunneling reaction step. In Part 2 of
this series, we present kinetic studies of the postphotolysis H atom reactions
with deuterated formic acid (DCOOD) to address this ambiguity. Short duration 193
nm in situ photolysis of DCOOD trapped in solid parahydrogen results in partial
depletion of the DCOOD precursor and photoproduction of primarily CO, CO2, DOCO,
HCO and mobile H atoms. At 1.9 K we observe post-irradiation growth in the
concentrations of DOCO and HCO that can be explained by H atom tunneling
reactions with DCOOD and CO, respectively. Conducting experiments with different
deuterium isotopomers of formic acid (DCOOD, DCOOH, HCOOD and HCOOH) provides
strong circumstantial evidence the reaction involves H atom abstraction from the
alkyl group of formic acid. Further, the anomalous temperature dependence
measured for the H + HCOOH reaction in Part 1 is also observed for the analogous
reactions with deuterated formic acid. The rate constants extracted for H atom
reactions with DCOOD and HCOOH are equivalent to within experimental uncertainty.
This lack of a kinetic isotope effect in the measured rate constant is
interpreted as evidence the reactions are diffusion limited; the measured rate
constant reflects the H atom diffusion rate and not the tunneling reaction rate.
Whether or not H atom reactions with chemical species in solid parahydrogen are
diffusion limited is one of the outstanding questions in this field, and this
work makes significant strides toward showing the reaction kinetics with formic
acid are diffusion limited.
PMID- 25113061
TI - Cellular inhibitors of apoptosis (cIAP) 1 and 2 are increased in placenta from
obese pregnant women.
AB - INTRODUCTION: Independent of their role in apoptosis, cellular inhibitors of
apoptosis (cIAP) 1 and 2, have emerged as regulators of inflammation. Obesity in
pregnancy is characterised by maternal and placental inflammation. Thus, the aim
of this study was to determine the effect of maternal obesity and pro
inflammatory mediators on cIAP expression in human placenta. METHODS: The
expression of cIAP was assessed in human placenta from lean (n = 15) and obese (n
= 14) patients by qRT-PCR and Western blotting. Primary trophoblast cells were
used to determine the effect of pro-inflammatory cytokines on cIAP expression,
and the effect of cIAP siRNA on pro-inflammatory cytokines. RESULTS: cIAP1 and
cIAP2, gene and protein expression were significantly higher in placenta from
women with pre-existing maternal obesity compared to placenta form lean women.
Additionally, bacterial endotoxin LPS and the pro-inflammatory cytokines tumour
necrosis factor (TNF)-alpha and interleukin (IL)-1beta significantly increased
the expression of both cIAP1 and cIAP2 in primary trophoblast cells isolated from
human term placenta. Knockdown of cIAP1 or cIAP2 in human primary trophoblast
cells significantly decreased TNF-alpha induced expression and secretion of pro
inflammatory cytokines IL-6 and IL-8 and of matrix metalloproteinase (MMP)-9.
DISCUSSION: cIAP1 and cIAP2 expression is increased in placenta from women with
pre-existing maternal obesity and in response to treatment with pro-inflammatory
cytokines. Functional studies in placental trophoblast cells revealed that cIAPs
are involved in TNF-alpha induced-expression of pro-inflammatory cytokines. Given
the central role of pro-inflammatory cytokines in placental nutrient transport,
this data suggest that cIAP1 and cIAP2 may play a role in fetal growth and
development.
PMID- 25113059
TI - Whole genome RNAi screens reveal a critical role of REV3 in coping with
replication stress.
AB - REV3, the catalytic subunit of translesion polymerase zeta (polzeta), is commonly
associated with DNA damage bypass and repair. Despite sharing accessory subunits
with replicative polymerase delta, very little is known about the role of polzeta
in DNA replication. We previously demonstrated that inhibition of REV3 expression
induces persistent DNA damage and growth arrest in cancer cells. To reveal
determinants of this sensitivity and obtain insights into the cellular function
of REV3, we performed whole human genome RNAi library screens aimed at
identification of synthetic lethal interactions with REV3 in A549 lung cancer
cells. The top confirmed hit was RRM1, the large subunit of ribonucleotide
reductase (RNR), a critical enzyme of de novo nucleotide synthesis. Treatment
with the RNR-inhibitor hydroxyurea (HU) synergistically increased the fraction of
REV3-deficient cells containing single stranded DNA (ssDNA) as indicated by an
increase in replication protein A (RPA). However, this increase was not
accompanied by accumulation of the DNA damage marker gammaH2AX suggesting a role
of REV3 in counteracting HU-induced replication stress (RS). Consistent with a
role of REV3 in DNA replication, increased RPA staining was confined to HU
treated S-phase cells. Additionally, we found genes related to RS to be
significantly enriched among the top hits of the synthetic sickness/lethality
(SSL) screen further corroborating the importance of REV3 for DNA replication
under conditions of RS.
PMID- 25113063
TI - Changes in length of the plantar aponeurosis during the stance phase of gait--an
in vivo dynamic fluoroscopic study.
AB - In locomotion, ligaments and muscles have been recognized to support the arch of
the foot. However, it remains unclear to what extent the passive and active
structures of the lower extremity support the longitudinal arch of the foot
during walking. In this study, the mechanical function of the plantar aponeurosis
(PA) is investigated by elongation measurements in vivo during the stance phase
of gait, in combination with measurements of the mechanical properties of the PA
in vitro. Fluoroscopy was used to measure the dynamic changes in PA length and
the angular motion of the metatarsophalangeal joint of the first ray, measured
during the stance phase (StPh) in 11 feet. Simultaneously, ground forces were
measured. Additionally, four cadaver feet delivered topographic information
relating to the PA, and three autopsy specimens of PA served to determine the in
vitro mechanical properties of PA. The present study revealed a non-significant
peak average PA shortening of 0.48% at about 32.5% StPh, followed by a
significant average peak elongation of 3.6% at 77.5% StPh. This average peak
elongation of 3.6% corresponds to a force of 292N, as estimated by mechanical
testing of the autopsy PA specimens. Considering the maximum peak elongation
measured in one volunteer of 4.8% at 76% StPh, a peak PA load of 488N might be
expected. Hence, with an average body weight of 751N, as allocated to the 11
investigated feet, this maximum peak force would correspond to about 0.65*body
weight. As far as we are aware, this is the first report on a dynamic
fluoroscopic study of the PA in gait with an appreciable number of feet (11
feet). In conclusion, muscles contribute to support of the longitudinal arch of
the foot and can possibly relax the PA during gait. The 'windlass effect' for
support of the arch in this context is therefore questionable.
PMID- 25113065
TI - Thromboembolic incidence with transiently elevated levels of coagulation factors
in patients with von Willebrand disease treated with VWF:FVIII concentrate during
surgery.
PMID- 25113066
TI - Somatic mosaicism for the COL7A1 mutation p.Gly2034Arg in the unaffected mother
of a patient with dystrophic epidermolysis bullosa pruriginosa.
AB - Dystrophic epidermolysis bullosa (DEB) is a heritable blistering disorder caused
by mutations in the type VII collagen gene, COL7A1. Although revertant mosaicism
is well known in DEB, 'forward' somatic mosaicism, in which a pathogenic mutation
arises on a wild-type (WT) background, extending beyond the germ cells, has not
been reported. It is therefore unknown what proportion of sporadic dominant DEB
(DDEB) cases result from de novo mutations or somatic mosaic parents. In the
clinically unaffected mother of a patient with DDEB pruriginosa due to the
p.Gly2034Arg mutation, we identified the p.Gly2034Arg mutation in a proportion of
lymphocytes and skin cells (mutational load 10-25%). Our data emphasize that
forward mosaicism occurs in DDEB and highlight that mutation analysis should
always be performed in the parents of sporadic DDEB patients to confirm the de
novo status of the mutation. Ultimately, this will reveal the frequency of true
de novo mutations and somatic mosaicism in parents, which has important
implications for genetic counselling. Our data indicate that the threshold of
mutant type VII procollagen to develop DDEB must be higher than 10-25%, which
provides a rationale for therapeutic approaches aimed at increasing the WT :
mutant type VII collagen ratio.
PMID- 25113067
TI - Parathyroid hormone may be an early predictor of low serum hemoglobin
concentration in patients with not advanced stages of chronic kidney disease.
AB - BACKGROUND: Parathyroid hormone (PTH) has been associated with anemia only in
dialysis patients with severe hyperparathyroidism. Whether an association between
PTH and hemoglobin also exists in patients with chronic kidney disease not on
dialysis (CKD-patients) is still unclear. In this study we evaluated the
association between PTH and hemoglobin in CKD-patients without severe secondary
hyperparathyroidism. METHODS: Hospitalized patients and outpatients (N = 979)
were retrospectively evaluated and categorized according to PTH quartile and
serum hemoglobin (<12.0, <11.0, <10.0 g/dl). Gender, diabetes, glomerular
filtration rate (GFR), hemoglobin, PTH, markers of mineral metabolism,
inflammation, iron status and nutrition were variables of adjustment in
univariate and multivariate analysis. RESULTS: An inverse association (p = 0.001)
was observed between PTH and hemoglobin in patients as a whole, in diabetics, and
in patients with GFR <=60 ml/min. PTH was the single predictor of low hemoglobin
in patients as a whole (unstandardized beta -2.12; p = 0.005), in diabetics
(unstandardized beta -8.86; p = 0.007) and in patients with GFR <=60 ml/min
(unstandardized beta -2.52; p = 0.006). For each increase of quartile of PTH the
risk of having hemoglobin level <10.0 mg/dl was more than doubled [hazard ratio
(HR) 2.79, 95% confidence interval (CI) 2.00-3.88; p = 0.001]. The receiver
operating characteristic curve showed that PTH >=122 pg/ml had 67% sensitivity
and 75% specificity in predicting hemoglobin level <10.0 g/dl with area under the
curve of 0.758 (95% CI 0.73-0.78). CONCLUSIONS: This study shows a significant
inverse association between PTH and hemoglobin levels across the whole spectrum
of non-dialysis CKD and a doubled risk of having serum hemoglobin <10.0 mg/dl in
the absence of severely deranged PTH concentration. These findings may have
clinical relevance in ascertaining the cause of unexplained low hemoglobin levels
in CKD-patients.
PMID- 25113068
TI - Applicability of the Chinese version of the 16-item Prodromal Questionnaire (CPQ
16) for identifying attenuated psychosis syndrome in a college population.
AB - AIM: The aim of this study was to examine the reliability, validity, sensitivity
and specificity of the Chinese version of the 16-item Prodromal Questionnaire
(CPQ-16) for identifying attenuated psychosis syndrome (APS) in a college
population. METHODS: The participants were recruited from a university. Five
hundred seventy-nine students completed the CPQ-16 and the Symptom Checklist-90.
One class (n = 79) was randomly selected to be retested with the CPQ-16 after 2
weeks. A randomly selected group of 49 individuals who tested positive and 50
individuals who tested negative were interviewed using the Structured Interview
for Prodromal Syndromes (SIPS). RESULTS: The internal consistency reliability was
good (Cronbach's alpha = 0.72). The test-retest reliability was 0.88. The total
score on the CPQ-16 was moderately to highly correlated with the total score on
the Symptom Checklist-90 and all of the subscales (r = 0.39-0.67, P < 0.001). A
cut-off CPQ-16 score of 9 was used to differentiate between those with a APS
diagnosis on the SIPS versus those with no SIPS diagnoses; this cut-off value
yielded 85% sensitivity, 87% specificity, a positive predictive value of 63% and
a positive likelihood ratio of 6.69. The area under the ROC curve (AUC) was
significant for the CPQ-16 total score (AUC = 0.93, SE = 0.026, 95% CI = 0.87
0.98, P < 0.001). Based on the proposed cut-off score, the CPQ-16 yielded a
positive rate of 5.0% (29/579). CONCLUSIONS: The CPQ-16, administered in a face
to-face interview, demonstrated high reliability and the ability to identify
college students at risk for psychosis.
PMID- 25113070
TI - Thermally induced structural rearrangement of the Fe(II) coordination geometry in
metallo-supramolecular polyelectrolytes.
AB - Rigid rod-type metallo-supramolecular coordination polyelectrolytes with Fe(II)
centres (Fe-MEPEs) are produced via the self-assembly of the ditopic ligand 1,4
bis(2,2':6',2''-terpyridine-4'-yl)benzene (tpy-ph-tpy) and Fe(II) acetate. Fe
MEPEs exhibit remarkable electrochromic properties; they change colour from blue
to transparent when an electric potential is applied. This electrochemical
process is generally reversible. The blue colour in the ground state is a result
of a metal-to-ligand charge transfer at the Fe(II) centre ion in a quasi
octahedral geometry. When annealed at temperatures above 100 degrees C, the blue
colour turns into green and the formerly reversible electrochromic properties are
lost, even after cooling down to room temperature. The thermally induced changes
in the Fe(II) coordination sphere are investigated in situ during annealing of a
solid Fe-MEPE using X-ray absorption fine structure (XAFS) spectroscopy. The
study reveals that the thermally induced transition is not accompanied by a redox
process at the Fe(II) centre. From the detailed analysis of the XAFS spectra, the
changes are attributed to structural changes in the coordination sphere of the
Fe(II) site. In the low temperature state, the Fe(II) ion rests in a quasi
octahedral coordination environment surrounded by six nitrogen atoms of the
pyridine rings. The axial Fe-N bond length is 1.94 A, while the equatorial bond
length amounts to 1.98 A. In the high temperature state, the FeN6-site exhibits a
distortion with the axial Fe-N bonds being shortened to 1.88 A and the equatorial
Fe-N bonds being elongated to 2.01 A.
PMID- 25113069
TI - Mycobacteria entry and trafficking into endothelial cells.
AB - Endothelial cells are susceptible to infection by mycobacteria, but the endocytic
mechanisms that mycobacteria exploit to enter host cells and their mechanisms of
intracellular transport are completely unknown. Using pharmacological inhibitors,
we determined that the internalization of Mycobacterium tuberculosis (MTB),
Mycobacterium smegmatis (MSM), and Mycobacterium abscessus (MAB) is dependent on
the cytoskeleton and is differentially inhibited by cytochalasin D, nocodazole,
cycloheximide, wortmannin, and amiloride. Using confocal microscopy, we
investigated their endosomal trafficking by analyzing Rab5, Rab7, LAMP-1, and
cathepsin D. Our results suggest that MSM exploits macropinocytosis to enter
endothelial cells and that the vacuoles containing these bacteria fuse with
lysosomes. Conversely, the entry of MTB seems to depend on more than one
endocytic route, and the observation that only a subset of the intracellular
bacilli was associated with phagolysosomes suggests that these bacteria are able
to inhibit endosomal maturation to persist intracellularly. The route of entry
for MAB depends mainly on microtubules, which suggests that MAB uses a different
trafficking pathway. However, MAB is also able to inhibit endosomal maturation
and can replicate intracellularly. Together, these findings provide the first
evidence that mycobacteria modulate proteins of host endothelial cells to enter
and persist within these cells.
PMID- 25113071
TI - Laparoscopic intraoperative navigation surgery for gastric cancer using real-time
rendered 3D CT images.
AB - PURPOSE: Recent advances in laparoscopic surgical technology have made it
possible to perform advanced high-level surgery, such as lymph node dissection
for malignancy. Grasping the anatomy during such procedures is important for a
safe operation. We have developed a new image information system that provides
three-dimensional (3D) reconstructed CT images synchronized with the motion of
the laparoscope. This study assesses this new navigation system. METHODS:
Enhanced CT using a custom-made software program can provide 3D angiography
images reconstructed as a laparoscopic view. A motion sensor mounted on the
laparoscope can detect the direction angle of the laparoscope. The real-time
rendered 3D CT images are synchronized with the laparoscopic video images
according to the motion of the scope. These 3D CT images are projected on another
monitor close to the laparoscopic video monitor. Lymph node dissection can be
performed with the help of the real-time navigation system that provides a
detailed 3D view of the vasculature. RESULTS: Ten laparoscopic gastrectomies were
performed using this navigation system. Real-time intraoperative navigation of
the vasculature was available, allowing for an excellent surgical outcome. No
complications occurred in this series. CONCLUSION: Our intraoperative navigation
system allows for safe laparoscopic gastric lymph node dissection.
PMID- 25113073
TI - Novel behaviors of multiferroic properties in Na-Doped BiFeO3 nanoparticles.
AB - Highly aliovalent Na(1+) ions were selected as the dopant to substitute Bi(3+)
ions in BiFeO3 (BFO) and Bi1-xNaxFeO3 (x = 0, 0.01, 0.03, 0.05) nanoparticles
prepared via a facile sol-gel method. Weak ferromagnetism and an obvious exchange
bias (EB) phenomenon without field cooling were observed in the samples. To
establish the presence of EB in the nanoparticles, training effect (TE) data were
analyzed using Binek's model. Moreover, with the increase in Na(1+) content, the
band gap was decreased, while interestingly, the leakage current density was
significantly reduced and the smallest leakage current density (~10(-7) A cm(-2))
was observed for the 3% Na-doped BFO. The electrical conduction mechanism of
samples was investigated by plotting log J versus log E. Oxygen vacancies
decreased with the increase of Na content analyzed through X-ray photoelectron
spectroscopy (XPS) measurements. To further explain the decrease of band gap and
leakage current density with the increase of Na content, the interplay of oxygen
vacancies and holes was analyzed and a phenomenological qualitative model based
on the electronic energy band proposed.
PMID- 25113074
TI - Synthesis of soluble, alkyne-substituted trideca- and hexadeca-starphenes.
AB - Two literature-known TIPS-ethynyl-dibromoacenes were prepared and employed to
synthesize cyclotrimers by using Yamamoto coupling conditions. Two large, well
soluble starphenes were isolated in good yields. Crystallographic
characterization verifies the triangular shape and shows significant differences
in crystal packing.
PMID- 25113072
TI - Hepatic resection for hepatocellular carcinoma in super-elderly patients aged 80
years and older in the first decade of the 21st century.
AB - PURPOSE: We evaluated the preoperative and postoperative characteristics and
prognosis of super-elderly patients with hepatocellular carcinoma (HCC). METHODS:
Four hundred and thirty-one patients who underwent hepatic resection for HCC were
classified into three groups according to their age at the time of surgery: super
elderly (>=80 years; n = 20), elderly (70-80 years; n = 172) and younger (<70
years; n = 239). We compared the clinical characteristics, preoperative and
postoperative factors and prognosis among the groups to evaluate whether liver
resection is appropriate for super-elderly patients. RESULTS: The liver function
was not significantly different among the groups. The proportion of patients with
preoperative cardiovascular and respiratory disease and hypertension was higher
in the super-elderly group compared to the other groups. The super-elderly group
had shorter operations and reduced hemorrhage rates compared to the other groups.
Postoperative cardiovascular complications and delirium were more frequently
observed in the super-elderly group. The overall and tumor-free survival rates
were not significantly different among the groups. Super-elderly patients had a
lower rate of liver or HCC-related death and a higher rate of death due to other
causes than the other groups. CONCLUSIONS: Super-elderly HCC patients who are
appropriately evaluated and selected might have a favorable prognosis after
undergoing hepatic resection.
PMID- 25113075
TI - Two-dimensional structured illumination microscopy.
AB - In widefield fluorescence microscopy, images from all but very flat samples
suffer from fluorescence emission from layers above or below the focal plane of
the objective lens. Structured illumination microscopy provides an elegant
approach to eliminate this unwanted image contribution. To this end a line grid
is projected onto the sample and phase images are taken at different positions of
the line grid. Using suitable algorithms 'quasi-confocal images' can be derived
from a given number of such phase-images. Here, we present an alternative
structured illumination microscopy approach, which employs two-dimensional
patterns instead of a one-dimensional one. While in one-dimensional structured
illumination microscopy the patterns are shifted orthogonally to the pattern
orientation, in our two-dimensional approach it is shifted at a single, pattern
dependent angle, yet it already achieves an isotropic power spectral density with
this unidirectional shift, which otherwise would require a combination of pattern
shift and -rotation. Moreover, our two-dimensional approach also yields a better
signal-to-noise ratio in the evaluated image.
PMID- 25113076
TI - Preventing Malaria among Children in Zambia: The Role of Mother's Knowledge.
AB - Malaria remains a devastating disease in Zambia, responsible for about 13% of
deaths among children under age 5. Lack of malaria-specific knowledge has been
commonly assumed to be an important barrier to engagement in behaviors that
prevent malaria. To the best of our knowledge, this is the first study that
accounts for the endogeneity of maternal knowledge in household's ownership of
insecticide-treated nets (ITN), child's use of ITN, and household's protection
against mosquitos (HSP). We account for the endogeneity of maternal knowledge
through discrete factor and standard instrumental variable estimators. We find
significant causal effects of maternal knowledge on the child's use of ITN and
HSP but no significant effect on ownership of ITN. The causal effects of maternal
knowledge on the use of ITN and HSP are strikingly larger in magnitude than the
effects in the reduced form models.
PMID- 25113077
TI - Is change in environmental supportiveness between primary and secondary school
associated with a decline in children's physical activity levels?
AB - Using a sample of English schoolchildren, we evaluate whether a change in school
local area environmental supportiveness between primary and secondary school is
associated with changes in active travel behaviours and physical activity levels.
Participant's activity levels and travel behaviours were recorded for a week
during their primary school final year and secondary school first year.
Environmental supportiveness was evaluated using a Geographical Information
System. Children attending both a primary and secondary school with a more
supportive local environment were more likely to maintain active travel
behaviours than those with less supportive environments. However, no trends were
apparent with change in school supportiveness and change in physical activity.
Policies that focus on the maintenance and uptake of active travel behaviours may
help maintain children's physical activity levels into adolescence.
PMID- 25113078
TI - Blood-brain barrier breakdown in reduced uterine perfusion pressure: a possible
model of posterior reversible encephalopathy syndrome.
AB - BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a clinical
entity characterized by headaches, altered mental status, seizures, and visual
disturbances and is associated with white matter vasogenic edema. There are no
experimental models to study PRES brain changes. METHODS: Twenty-eight pregnant
Wistar rats were divided into 4 groups of 7: (1) pregnant-control; (2) reduced
uterine perfusion pressure (RUPP); (3) invasive blood pressure (IBP); and (4)
reduced uterine perfusion pressure plus invasive blood pressure (RUPP-IBP). The
RUPP and RUPP-IBP groups were submitted to a reduction of uterine perfusion
pressure at pregnancy days 13 to 15. The invasive mean arterial pressure of the
IBP and RUPP-IBP groups was measured on day 20. The blood-brain barriers (BBBs)
of all groups were analyzed using 2% Evans Blue dye on day 21. RESULTS: RUPP rats
had higher blood pressures and increased BBB permeability to Evans Blue dye
compared with the control animals. Brain staining occurred in 11 of 14 RUPP rats
and in none of the control groups (P < .0001). CONCLUSIONS: The physiopathology
of PRES remains unclear. Here, we described the use of RUPP rats as a potential
model to better comprehend this syndrome.
PMID- 25113079
TI - Investigating the utility of previously developed prediction scores in acute
ischemic stroke patients in the stroke belt.
AB - BACKGROUND: To assess the utility of previously developed scoring systems, we
compared SEDAN, named after the components of the score (baseline blood Sugar,
Early infarct signs and (hyper) Dense cerebral artery sign on admission computed
tomography scan, Age, and National Institutes of Health Stroke Scale on
admission), Totaled Health Risks in Vascular Events (THRIVE), Houston Intra
arterial Therapy (HIAT), and HIAT-2 scoring systems among patients receiving
systemic (intravenous [IV] tissue plasminogen activator [tPA]) and endovascular
(intra-arterial [IA]) treatments. METHODS: We retrospectively reviewed all IV tPA
and IA patients presenting to our center from 2008-2011. The scores were assessed
in patients who were treated with IV tPA only, IA only, and a combination of IV
tPA and IA (IV-IA). We tested the ability of THRIVE to predict discharge modified
Rankin scale (mRS) 3-6, HIAT and HIAT-2 discharge mRS 4-6, and SEDAN symptomatic
intracerebral hemorrhage (sICH). RESULTS: Of the 366 patients who were included
in this study, 243 had IV tPA only, 89 had IA only, and 34 had IV-IA. THRIVE was
predictive of mRS 3-6 in the IV-IA (odds ratio [OR], 1.95; 95% confidence
interval [CI], 1.30-2.91) and the IV group (OR, 1.71; 95% CI, 1.43-2.04), but not
in the IA group. HIAT was predictive of mRS 4-6 in the IA (OR, 3.55; 95% CI, 1.65
7.25), IV (OR, 3.47; 95% CI, 2.26-5.33), and IV-IA group (OR, 6.48; 95% CI, 1.41
29.71). HIAT-2 was predictive of mRS 4-6 in the IA (OR, 1.39; 95% CI, 1.03-1.87)
and IV group (OR, 1.36; 95% CI, 1.18-1.57), but not in the IV-IA group. SEDAN was
not predictive of sICH in the IA or the IV-IA group, but was predictive in the IV
group (OR, 1.54; 95% CI, 1.01-2.36). CONCLUSIONS: Our study demonstrated that
although highly predictive of outcome in the original study design treatment
groups, prediction scores may not generalize to all patient samples, highlighting
the importance of validating prediction scores in diverse samples.
PMID- 25113081
TI - Stroke-induced immune depression-a randomized case control study in Kashmiri
population of North India.
AB - BACKGROUND: Stroke leads to transient immunedepression, which leads to increased
incidence of poststroke infections. Because infection is one of the most common
causes of increased mortality in patients with stroke, this study was undertaken
to document immunedepression after stroke in our population. METHODS: A case
controlled study wherein 39 patients with acute ischemic stroke in the age group
of 18 and 60 years without any evidence of previous immunedepression were
included. Interleukin 6 (IL-6) and interleukin 10 (IL-10) levels were checked in
plasma in both the groups on day 3 and day 45. Also Cortisol and epinephrine
levels were checked in the urine samples collected on day 3 and day 8. RESULTS:
No significant difference was seen between the IL-6 and the IL-10 levels in
samples collected on day 3 between the controls and cases, whereas Cortisol and
norepinephrine were significantly raised in samples collected on day 3 in cases
who developed infection as compared with controls. CONCLUSIONS: The higher levels
of urinary cortisol and norepinephrine were observed in patients with stroke who
developed infections, which indirectly reflected increased amount of stroke
related stress. Furthermore, the levels of plasma IL-6 and IL-10 were also
elevated in the same group of patients, which means transformation of
immunecompetence to immunedepression, which is responsible for higher mortality.
Subsequently on recovery from infection the plasma levels of interleukins and
urinary cortisol and norepinephrine did not show any difference, which indirectly
means recovery of the immune system on recovery from acute stage of stroke.
Mortality in the patients with infection was increased than controls.
PMID- 25113080
TI - Intravenously administered tissue plasminogen activator useful in milder strokes?
A meta-analysis.
AB - BACKGROUND: The dilemma of whether to treat mild strokes with tPA is a chronic
problem. We performed a meta-analysis and metaregression of the published
literature to determine the best definition of mild strokes and if intravenously
administered tissue plasminogen activator (IV-tPA) is beneficial. METHODS:
PubMed, Embase, Science Direct, and Cochrane CENTRAL were searched from inception
to May 2013. The search terms used were "stroke," "cerebral infarct," "mild
stroke," "minor stroke," "small infarct," "modified Rankin scale," "National
Institutes of Health Stroke Scale (NIHSS) score," "stroke thrombolysis," and
their combinations. Studies were included if they (1) involved 5 or more human
patients with stroke; (2) analyzed modified Rankin scale (mRS) scores as the main
variables of interest; (3) presented outcomes for NIHSS scores less than 6, 5, 4,
or 3 points. Good outcomes were defined as mRS scores 0-1, and other outcomes
studied were intracranial hemorrhage and mortality. RESULTS: Of 894 articles, 30
articles met our criteria. Only 8 articles provided patients arms with and
without tPA treatment. A total of 637 patients with IV-tPA treatment and 568
without thrombolysis were included in analysis. Good outcomes were associated
with tPA and just reached statistical significance (pooled odds ratio [OR],
1.319; 95% confidence interval [CI], 1.004-1.733; z = 1.987; P = .047). There
were moderate levels of heterogeneity between studies (tau(2) = .346; Q = 19.974;
df = 7; P = .006; I(2) = 64.954). On metaregression of a-priori sources of
heterogeneity within individuals, we found age (B = -.37; z = -2.496; P = .012)
to be a significant moderator. Mortality was not significantly different between
IV-tPA-treated and nonthrombolyzed groups (pooled OR 1.095; 95% CI, .438-2.738; z
= .193; P = .847). CONCLUSIONS: Patients with mild stroke may derive benefit from
intravenous thrombolysis without a significant increase in mortality.
PMID- 25113082
TI - Poor awareness of stroke--a hospital-based study from South India: an urgent need
for awareness programs.
AB - BACKGROUND: Stroke treatment has reached a new benchmark with thrombolytic
therapy. However, India has witnessed a tremendous increase in morbidity and
mortality of stroke over the past few decades. The prime deciding factor is
initiation of treatment within the time window, which requires early recognition
of stroke symptoms. We wished to analyze the lacunae in the stroke knowledge in
our population. This hospital-based study assessed awareness of the public
regarding stroke. METHODS: Two trained medical students interviewed accompanying
relatives using a structured questionnaire. Data were analyzed using Statistical
Package for the Social Sciences, version 20. Univariate and multivariate analyses
were done. Descriptive results are presented as mean +/- SD. P less than .05 was
considered as statistically significant. RESULTS: In total, 350 individuals
formed the study group; mean age was 40.23 +/- 13.4 years constituting 145 males
(47.5%) and 205 females (58.5%). Only 50 (14%) respondents could identify that
the patient had developed stroke; however, 35% respondents identified brain as
the organ involved for the presenting complaints and 34% could identify the
warning symptoms of stroke, limb weakness being the most common (30%). Sources of
information were friends and media (8%). Median time of reaching the hospital was
10 hours with patients transported by ambulance reaching early (P < .03); 80% of
patients were fed in drowsy state during transport. More than 50% of the
respondents were not able to identify the risk factors nor were aware that stroke
is a preventable or a life-threatening disease. Multivariate logistic regression
analysis confirmed that higher level of education was the only variable, which
correlated with the organ identification (P < .001), stroke recognition (P <
.002), and identification of the warning symptoms (P < .001). CONCLUSIONS: This
hospital-based study reveals that there is a poor knowledge of recognition of
stroke, its warning signs, risk factors, and prehospital care. There is an urgent
need to design stroke awareness programs in the country with emphasis on
ambulance service to minimize the time to thrombolysis.
PMID- 25113083
TI - Predicting walking function of patients one month poststroke using modified
Rivermead mobility index on admission.
AB - Being able to predict walking ability of patients with stroke at an early stage
is useful in formulating realistic rehabilitation goals and facilitating early
discharge planning, which are beneficial not only to the patients but their
family members and health care providers. This study aimed to use the modified
Rivermead mobility index (MRMI) of the stroke patients on day 3 of their
admission to predict their independent walking ability on day 28 postadmission. A
total of 232 patients with acute stroke who were admitted to the acute hospital
were recruited. Fifty-three percent of them (n = 123) were able to achieve
independent walking ability after 28 days of admission whereas 47.0% of them (n =
109) failed to do so. The receiver operating characteristics curve analysis was
performed. The optimal cutoff score with the highest sum of sensitivity and
specificity was found to be 18.5 (sensitivity, 85.0%; specificity, 75.0%) and the
area under the curve was .880. In conclusion, MRMI on day 3 of admission maybe
useful in predicting independent walking ability 1 month after stroke.
PMID- 25113085
TI - The impact of prior antithrombotic status on cerebral infarction in patients with
atrial fibrillation.
AB - BACKGROUND: Anticoagulation effectively prevents cardioembolic stroke in atrial
fibrillation (AF) patients, whereas it is less effective than antiplatelet
therapy (AT) in noncardioembolic stroke prevention. We hypothesized that the
ischemic lesion pattern and vascular patency would differ according to the
antithrombotic treatment status in AF patients. METHODS: The medical records of
1078 acute ischemic stroke patients with AF were retrospectively reviewed.
Patients were classified according to medication at stroke onset: (1) optimal
anticoagulation (OAC; international normalized ratio [INR] 1.7-3.0; n = 36); (2)
suboptimal anticoagulation (SOAC; INR <=1.7; n = 134); (3) AT (n = 285); and (4)
control (no antithrombotic medication; n = 623). Imaging and clinical variables
of each group were compared with that of controls. RESULTS: Small cortical or
single subcortical infarctions were more common in the OAC group than in controls
(6% vs. 1% and 22% vs. 8%, respectively; standardized residual, 2.4 and 2.8).
Multicirculatory infarctions were less common in the OAC group than in controls
(0% vs. 11%; standardized residual, -2.0). Obstruction of the corresponding
artery was less common in the OAC group than in controls (26.5% vs. 46.5%, P =
.02). Initial neurologic severity was lower in the OAC and AT groups than in
controls (P = .01 and .03, respectively). OAC and AT were independently
associated with favorable functional outcome at 3-months (P = .015 and <.001,
respectively). CONCLUSIONS: Ischemic stroke can occur during OAC in AF patients.
Small cortical or single subcortical lesions were more common than typical
cardioembolic lesion patterns. OAC and AT were protective against severe
neurologic deficit and independently associated with favorable outcome, but SOAC
was not.
PMID- 25113084
TI - Intravenous fibrinolysis eligibility: a survey of stroke clinicians' practice
patterns and review of the literature.
AB - BACKGROUND: The indications and contraindications for intravenous (IV)
recombinant tissue plasminogen activator (rtPA) use in ischemic stroke can be
confusing to the practicing neurologist. Here we seek to describe practice
patterns regarding decision-making among US stroke clinicians. METHODS: Stroke
clinicians (attending and fellow) from the 8 National Institutes of Health
SPOTRIAS (Specialized Programs of Translational Research in Acute Stroke) centers
were asked to complete a survey ahead of the 2012 SPOTRIAS Investigators'
meeting. RESULTS: A total of 51 surveys were collected (71% response rate). Most
of the responders were attending physicians (68%). Only 18% of clinicians
reported strictly adhering to current American Heart Association guidelines for
treatment within 3 hours from symptom onset; this increased to 51% for the
European Cooperative Acute Stroke Study (ECASS) III criteria in the 3 to 4.5
hours time frame. All clinicians treat eligible patients in the 3 to 4.5 hours
time frame. The great majority will recommend rtPA in the following scenarios:
(1) elderly individuals irrespective of age (97%); (2) severe stroke irrespective
of National Institutes of Health Stroke Scale (NIHSS) (95%); or (3) suspected
stroke with seizures at symptom onset (91%). None recommended rtPA in the setting
of an international normalized ratio >1.7. Most clinicians defined mild strokes
as an exclusion based on the perceived disability of the deficit (80%) rather
than on a specific NIHSS threshold. CONCLUSIONS: Most surveyed stroke clinicians
seem to find that the current IV rtPA eligibility criteria for the 3-hour time
frame too restrictive. All would recommend rtPA to eligible patients in the 3 to
4.5 hours time frame despite the absence of an U.S. Food and Drug Administration
(FDA)-approved indication.
PMID- 25113087
TI - Revision of Beardius Reiss et Sublette, 1985 (Diptera: Chironomidae), with the
description of twenty new species.
AB - The genus Beardius Reiss et Sublette, 1985 is revised and twenty new species,
Beardius abbadi sp. n., B. arawak sp. n., B. bizzoi sp. n., B. bucephalus sp. n.,
B. curticaudatus sp. n., B. dioi sp. n., B. hirtidorsum sp. n., B. krenak sp. n.,
B. kumadueni sp. n., B. longicaudatus sp. n., B. mileneae sp. n., B. nebularius
sp. n., B. neusae sp. n., B. novoairensis sp. n., B. phoenix sp. n., B. sapiranga
sp. n., B. tupinamba sp. n., B. vanessae sp. n., and B. yperoig sp. n. from
Brazil and Beardius chapala sp. n. from Mexico are described and figured.
Further, the female, pupa and larva of B. urupeatan Pinho, Mendes et Andersen and
the female and larva of B. cristhinae Trivinho-Strixino et Siqueira are
described, and new records of Brazilian species are provided. Emended diagnoses
for all stages and sexes are given. The phylogeny of the genus is outlined and
seven tentative species groups, the parcus group, the truncatus group, the
tupinamba group, the triangulatus group, the bucephalus group, the xylophilus
group, and the roquei group, are proposed. Keys to males, females, pupae and
larvae are provided.
PMID- 25113086
TI - Over-the-counter and prescription sleep medication and incident stroke: the
REasons for Geographic and Racial Differences in Stroke study.
AB - BACKGROUND: Preliminary evidence suggests sleep medications are associated with
risk of vascular events; however, the long-term vascular consequences are
understudied. This study investigated the relation between sleep medication use
and incident stroke. METHODS: Within the REasons for Geographic And Racial
Differences in Stroke study, 21,678 black participants and white participants
(>=45 years) with no history of stroke were studied. Participants were recruited
from 2003 to 2007. From 2008 to 2010, participants self reported their
prescription and over-the-counter sleep medication use over the past month.
Suspected stroke events were identified by telephone contact at 6-month intervals
and associated medical records were retrieved and physician-adjudicated.
Proportional hazards analysis was used to estimate hazard ratios for incident
stroke associated with sleep medication use (0, 1-14, and 15+ days per month)
controlling for sociodemographics, stroke risk factors, mental health symptoms,
and sleep apnea risk. RESULTS: At the sleep assessment, 9.6% of the sample used
prescription sleep medication and 11.1% used over-the-counter sleep aids. Over an
average follow-up of 3.3 +/- 1.0 years, 297 stroke events occurred. Over-the
counter sleep medication use was associated with increased risk of incident
stroke in a frequency-response relationship (P = .014), with a 46% increased risk
for 1-14 days of use per month (hazards ratio [HR] = 1.46; 95% confidence
interval [CI], .99-2.15) and a 65% increased risk for 15+ days (HR = 1.65; 95%
CI, .96-2.85). There was no significant association with prescription sleep
medications (P = .80). CONCLUSIONS: Over-the-counter sleep medication use may
independently increase the risk of stroke beyond other risk factors in middle
aged to older individuals with no history of stroke.
PMID- 25113088
TI - Watching individual molecules flex within lipid membranes using SERS.
AB - Interrogating individual molecules within bio-membranes is key to deepening our
understanding of biological processes essential for life. Using Raman
spectroscopy to map molecular vibrations is ideal to non-destructively
'fingerprint' biomolecules for dynamic information on their molecular structure,
composition and conformation. Such tag-free tracking of molecules within lipid
bio-membranes can directly connect structure and function. In this paper, stable
co-assembly with gold nano-components in a 'nanoparticle-on-mirror' geometry
strongly enhances the local optical field and reduces the volume probed to a few
nm(3), enabling repeated measurements for many tens of minutes on the same
molecules. The intense gap plasmons are assembled around model bio-membranes
providing molecular identification of the diffusing lipids. Our experiments
clearly evidence measurement of individual lipids flexing through telltale rapid
correlated vibrational shifts and intensity fluctuations in the Raman spectrum.
These track molecules that undergo bending and conformational changes within the
probe volume, through their interactions with the environment. This technique
allows for in situ high-speed single-molecule investigations of the molecules
embedded within lipid bio-membranes. It thus offers a new way to investigate the
hidden dynamics of cell membranes important to a myriad of life processes.
PMID- 25113090
TI - [Surgical characteristics of small parathyroid gland adenomas].
PMID- 25113089
TI - [Shoulder dislocation in athletes].
AB - BACKGROUND: Shoulder dislocation is a common injury in athletes. Surgical and non
surgical therapy options are still the subject of controversial debate. STUDY
AIM: This article presents important considerations for decision-making and
current concepts for the therapy of shoulder dislocation in athletes. METHODS: A
selective literature search was carried out in PubMed. RESULTS: Surgical and non
surgical therapy options are described in the literature without yet defining a
gold standard. CONCLUSION: Early surgical stabilization is currently recommended
in young athletes. For decision-making numerous sport and patient-related factors
need to be considered. Most athletes are able to return to the pre-injury level
after surgical stabilization.
PMID- 25113091
TI - [Perioperative treatment with pasireotide reduces the rate of postoperative
pancreatic fistula].
PMID- 25113093
TI - Detection of the motor points of the abdominal muscles.
AB - PURPOSE: Abdominal functional electrical stimulation (AFES) is a technique
intended to improve respiratory function in tetraplegia where breathing is
affected due to abdominal muscle paralysis. Although it is known that optimal
muscle contraction is achieved when electrical stimulation is applied close to
the muscle motor point, AFES studies have used a variety of electrode positions.
This study aims to investigate the feasibility of using Neuromuscular Electrical
Stimulation to detect the motor points of the abdominal muscles, and to evaluate
the intrasubject repeatability and intersubject uniformity of their positions, to
find the most suitable AFES electrode location. METHODS: Low frequency
stimulation (0.5 Hz) was applied to the abdominal muscles of 10 able bodied and
five tetraplegic participants. The electrode positions which achieved the
strongest muscle contractions were recorded as the motor point positions, with
measurements repeated once. For five able bodied participants, assessments were
repeated after 18 months, in seated and supine positions. RESULTS: Intersubject
uniformity ranged from 2.8 to 8.8%. Motor point positions were identified with
intrasubject repeatability of <1.7 cm, deemed adequate relative to standard AFES
electrode size. Intrasubject repeatability shows motor point positions changed
little (<1.7 cm) after 18 months but varied between seated and supine positions
with repeatability of up to 3.1 cm. CONCLUSIONS: A simple technique to locate the
motor points of the abdominal muscles is presented and shown to have an adequate
intrasubject repeatability, enabling the optimum AFES electrode location to be
identified for each user.
PMID- 25113094
TI - Reliability of H-reflex in vastus lateralis and vastus medialis muscles during
passive and active isometric conditions.
AB - PURPOSE: This study aimed to evaluate the modulation and reliability of the
vastus medialis (VM) and vastus lateralis (VL) H-reflexes in both passive and
active conditions. METHODS: Recruitment curves of VM and VL H-reflexes and M
waves at rest and during muscle contraction (30% of maximal voluntary
contraction) were performed for 12 healthy males and were then repeated after 1
h, 1 day and 1 week. The maximal H-reflexes of each muscle were normalized to
their respective maximal M-waves (H/M ratio) and absolute (CV) and relative (ICC)
reliability were calculated. RESULTS: The H-reflex was potentiated in active
compared to passive condition and a higher H-reflex occurrence (12 vs. 10
subjects) and amplitude (~+150%) was found for the VM compared to the VL in
active condition. The intra- (ICChour = 0.97) and inter-day (ICCday = 0.92;
ICCweek = 0.92) reliability was poor for the passive VM H/M ratio due to high
within-subject variations (CVhour = 52.2%; CVday = 69.8%; CVweek = 60.9%) whereas
for the active condition the reliability, especially intra-day, was good (ICChour
= 0.93 and CVhour = 12%; ICCday = 0.86 and CVday = 14.5%; ICCweek = 0.79 and
CVweek = 19.7%). CONCLUSIONS: This study showed differential modulation of the H
reflex between vasti muscles of the quadriceps and a higher occurrence and
reliability for the active VM H-reflex. One can therefore conclude that it seems
more appropriate to evoke quadriceps VM H-reflex (rather than VL) during an
isometric muscle contraction.
PMID- 25113095
TI - High-dose inhaled terbutaline increases muscle strength and enhances maximal
sprint performance in trained men.
AB - PURPOSE: The purpose of the present study was to investigate the effect of high
dose inhaled terbutaline on muscle strength, maximal sprinting, and time-trial
performance in trained men. METHODS: Nine non-asthmatic males with a VSO2max of
58.9 +/- 3.1 ml min(-1) kg(-1) (mean +/- SEM) participated in a double-blinded
randomized crossover study. After administration of inhaled terbutaline (30 * 0.5
mg) or placebo, subjects' maximal voluntary isometric contraction (MVC) of
m.quadriceps was measured. After MVC, subjects performed a 30-s Wingate test.
Sixty minutes following the Wingate test, subjects exercised for 10 min at 80% of
VSO2max and completed a 100-kcal time trial. Aerobic contribution was determined
during the Wingate test by indirect calorimetry. Furthermore, plasma terbutaline,
lactate, glucose, and K(+) were measured. RESULTS: Inhalation of 15 mg
terbutaline resulted in systemic concentrations of terbutaline of 23.6 +/- 1.1 ng
ml(-1) 30 min after administration, and elevated plasma lactate (P = 0.001) and
glucose (P = 0.007). MVC was higher for terbutaline than placebo (738 +/- 64 vs.
681 +/- 68 N) (P = 0.007). In addition, Wingate peak power and mean power were
2.2 +/- 0.8 (P = 0.019) and 3.3 +/- 1.0% (P = 0.009) higher for terbutaline than
placebo. Net accumulation of plasma lactate was higher (P = 0.003) for
terbutaline than placebo during the Wingate test, whereas [Formula: see text]
above baseline was unchanged by terbutaline (P = 0.882). Time-trial performance
was not different between treatments (P = 0.236). CONCLUSION: High-dose inhaled
terbutaline elicits a systemic response that enhances muscle strength and sprint
performance. High-dose terbutaline should therefore continue to be restricted in
competitive sport.
PMID- 25113097
TI - Muscle activation during low- versus high-load resistance training in well
trained men.
AB - PURPOSE: It has been hypothesized that lifting light loads to muscular failure
will activate the full spectrum of MUs and thus bring about muscular adaptations
similar to high-load training. The purpose of this study was to investigate EMG
activity during low- versus high-load training during performance of a multi
joint exercise by well-trained subjects. METHODS: Employing a within-subject
design, 10 young, resistance-trained men performed sets of the leg press at
different intensities of load: a high-load (HL) set at 75% of 1-RM and a low-load
(LL) set at 30% of 1-RM. The order of performance of the exercises was
counterbalanced between participants, so that half of the subjects performed LL
first and the other half performed HL first, separated by 15 min rest. Surface
electromyography (EMG) was used to assess mean and peak muscle activation of the
vastus medialis, vastus lateralis, rectus femoris, and biceps femoris. RESULTS:
Significant main effects for trials and muscles were found (p < 0.01).
Significantly greater peak EMG activity was found during the HL set (M = 177.3,
SD = 89.53) compared to the LL set (M = 137.73, SD = 95.35). Significantly
greater mean EMG activity was found during the HL set (M = 63.7, SD = 37.23)
compared to the LL set (M = 41.63, SD = 28.03). CONCLUSIONS: Results indicate
that training with a load of 30% 1-RM to momentary muscular failure does not
maximally activate the full motor unit pool of the quadriceps femoris and
hamstrings during performance of multi-joint lower body exercise.
PMID- 25113098
TI - Origin, patterns and anthropogenic accumulation of potentially toxic elements
(PTEs) in surface sediments of the Aviles estuary (Asturias, northern Spain).
AB - Sediment quality has been assessed within the Aviles estuary, an important
industrial area in the NW of Spain. The study started with a geochemical
characterization of the superficial sediments that revealed some anomalous
metal(oid)s concentrations in sensitive areas such as beaches or dunes. These
data were studied by means of multivariate statistical techniques and enrichment
factors calculation to evaluate the correlations and geochemical origin within
the different elements. A novel approach using the combination of enrichment
factors with a sequential application of factor analysis, clustering and kriging
was essential to identify the possible sources of pollution. The collected
information suggested that Cd (strongly correlated with Zn and Pb) was the
potentially toxic element most widely distributed and problematic. Furthermore,
particulate emissions from Zn metallurgy, as well as dust generated by the
mineral loading and stockpile activities in the port were identified as the most
important sources of pollution.
PMID- 25113099
TI - Resilience of branching and massive corals to wave loading under sea level rise-
a coupled computational fluid dynamics-structural analysis.
AB - Measurements of coral structural strength are coupled with a fluid dynamics
structural analysis to investigate the resilience of coral to wave loading under
sea level rise and a typical Great Barrier Reef lagoon wave climate. The measured
structural properties were used to determine the wave conditions and flow
velocities that lead to structural failure. Hydrodynamic modelling was
subsequently used to investigate the type of the bathymetry where coral is most
vulnerable to breakage under cyclonic wave conditions, and how sea level rise
(SLR) changes this vulnerability. Massive corals are determined not to be
vulnerable to wave induced structural damage, whereas branching corals are
susceptible at wave induced orbital velocities exceeding 0.5m/s. Model results
from a large suite of idealised bathymetry suggest that SLR of 1m or a loss of
skeleton strength of order 25% significantly increases the area of reef flat
where branching corals are exposed to damaging wave induced flows.
PMID- 25113101
TI - Evaluation of potential relationships between benthic community structure and
toxic metals in Laizhou Bay.
AB - The objective of the present study was to examine the relationships between
benthic community structure and toxic metals using bivariate/multivariate
techniques at 17 sediment locations in Laizhou Bay, North China. Sediment
chemical data were evaluated against geochemical background values and sediment
quality guidelines, which identified Cu and As as contaminants of concern with a
moderate potential for adverse effects. Benthic community data were subjected to
non-metric multidimensional scaling, which generated four groups of stations.
Spearman rank correlation was then employed to explore the relationships between
the major axes of heavy metals and benthic community structure. However, weak and
insignificant correlations were found between these axes, indicating that
contaminants of concern may not be the primary explanatory factors. Polychaeta
were abundant in southern Laizhou Bay, serving as a warning regarding the health
status of the ecosystem. Integrated sediment quality assessment showed sediments
from northern central locations were impaired, displaying less diverse benthos
and higher metal contamination.
PMID- 25113102
TI - Trace metal variability, background levels and pollution status assessment in
line with the water framework and Marine Strategy Framework EU Directives in the
waters of a heavily impacted Mediterranean Gulf.
AB - The aim of this work is to assess trace metal pollution status (Cd, Cu, Ni, Pb,
Zn) in the waters of Saronikos Gulf, Greece, in line with the WFD and MSFD
European Directives, based on data collected over a decade (2000-2010). Dissolved
metal background levels are estimated for the first time for Greek marine waters
and the upper limits are: Cd: 0.574 nmol L(-1); Cu: 8.26 nmol L(-1); Ni: 7.94
nmol L(-1); Pb: 2.60 nmol L(-1); Zn: 115 nmol L(-1). The variability of dissolved
and particulate metals reflected the presence of several point sources and
revealed the importance of natural mechanisms acting as non-point sources. The
status of Saronikos Gulf is classified as 'High' for most metals studied. An
exception to this is the enclosed Elefsis Bay where Cu, Ni and Zn concentrations
are found above background. Our work will assist the implementation of WFD and
MSFD directives in Greece.
PMID- 25113100
TI - Decalcification of benthic foraminifera due to "Hebei Spirit" oil spill, Korea.
AB - In order to determine the effects on foraminifera due to spilled crude oil in the
"Herbei Spirit" incident, a study of benthic foraminiferal assemblages was
carried out on sediment samples collected from the Sogeunri tidal flat, Taean
Peninsula, Korea. Breakages of the chambers in the Ammonia beccarii and Elphidium
subincertum species of the Sogeunri tidal flat with a low pH (6.98 on average)
were marked. These chamber breakages occurred in 71.6% of A. beccarii and are
thought to be caused by decalcification due to the fall in pH resulting from the
"Hebei Spirit" oil spill. The factors that affect breakage of the chamber in
benthic foraminifera under low pH condition may be not only deto decalcification
but also to exposure duration of substrata in the tidal flat spilled crude oil.
PMID- 25113103
TI - A three-step model to assess shoreline and offshore susceptibility to oil spills:
the South Aegean (Crete) as an analogue for confined marine basins.
AB - This study combines bathymetric, geomorphological, geological data and oil spill
predictions to model the impact of oil spills in two accident scenarios from
offshore Crete, Eastern Mediterranean. The aim is to present a new three-step
method of use by emergency teams and local authorities in the assessment of
shoreline and offshore susceptibility to oil spills. The three-step method
comprises: (1) real-time analyses of bathymetric, geomorphological, geological
and oceanographic data; (2) oil dispersion simulations under known wind and sea
current conditions; and (3) the compilation of final hazard maps based on
information from (1) and (2) and on shoreline susceptibility data. The results in
this paper show that zones of high to very-high susceptibility around the island
of Crete are related to: (a) offshore bathymetric features, including the
presence of offshore scarps and seamounts; (b) shoreline geology, and (c) the
presence near the shore of sedimentary basins filled with unconsolidated deposits
of high permeability. Oil spills, under particular weather and oceanographic
conditions, may quickly spread and reach the shoreline 5-96 h after the initial
accident. As a corollary of this work, we present the South Aegean region around
Crete as a valid case-study for confined marine basins, narrow seaways, or
interior seas around island groups.
PMID- 25113104
TI - Uncertainty analysis of total phosphorus spatial-temporal variations in the
Yangtze River Estuary using different interpolation methods.
AB - Interpolation processes and results are generally accompanied by uncertainty
which affects the spatial and temporal properties of pollutants. Based on the 4
period sample data of total phosphorus (TP) collected from the Yangtze River
Estuary (YRE) in 2010 and 2011, the uncertainty of spatial-temporal variation was
analyzed with interpolation methods of inverse distance weighted (IDW), local
polynomial interpolation (LPI), ordinary kriging (OK) and disjunctive kriging
(DK). The root mean square errors (RMSE) and the mean relative errors (MRE) were
used to analyze the accuracy of different interpolation methods. The results
showed that the uncertainty of DK was the lowest and the uncertainty of LPI was
the highest among the 4 methods. The subtraction results between different
interpolation methods showed that there was some distinct area of value in the
disparate interval (not in [-0.05, 0.05] (mg/L)) in the 4 seasonal results, which
was mainly distributed in the boundary region and around some sample sites. Both
standard deviation (SD) and coefficient of variance (CV) in August 2010 were the
highest in the 4 seasons and annual mean. The uncertainty may be caused by choice
of interpolation methods, spatial data discrepancy and the lack of sample data.
PMID- 25113105
TI - [Is invasive therapy (medically/ethically) justifiable nearing an end of life
situation, if it is based on symptom control and quality of life?].
AB - On the basis of a case study, the complex problems of an invasive therapy
(gastroscopy with stentig) in an end of life situation will be demonstrated and
discussed. The main problems of the 67-year-old patient with a gastric cardia
carcinoma were the symptoms of nausea and vomiting, which were managed well with
conservative treatment. The wish from the patient to eat was a highly ethical
demand on the team of the palliative care unit. This paper shows the area of
tension between the highly developed interventional endoscopic capabilities on
the one hand and the reasonable treatment in end of life situations on the other.
PMID- 25113106
TI - Master apical file size - smaller or larger: a systematic review of healing
outcomes.
AB - The purpose of this systematic review was to determine in patients undergoing
root canal treatment, whether apical enlargement affected the healing outcome. A
PICO (population, intervention, comparison and outcome) strategy was developed to
identify studies dealing with apical size of canal and healing outcome as
measured clinically and radiographically. The MEDLINE, Embase, Cochrane and
PubMed databases were searched. Additionally, the bibliography of all relevant
articles and textbooks was manually searched. Based on inclusion and exclusion
criteria, two reviewers independently selected the relevant articles. Four
articles were identified that met the inclusion criteria. There were no studies
that evaluated apical enlargement and healing outcome using cone beam computed
tomography. The results of the systematic review confirmed that more evidence
based research in this area is needed. With the limited information available,
the best current available clinical evidence suggests that for patients with
necrotic pulps and periapical lesions, enlargement of the apical size would
result in an increased healing outcome in terms of clinical and radiographic
evaluations.
PMID- 25113108
TI - Group conformity: the legacy continues.
PMID- 25113109
TI - Medical schools: what counts as one, and why count them?
PMID- 25113110
TI - Revealing the hidden curriculum and reducing cultural reproduction: small steps
on a long road.
PMID- 25113111
TI - When I say ... preparedness.
PMID- 25113112
TI - The good and bad of group conformity: a call for a new programme of research in
medical education.
AB - CONTEXT: Given that a significant portion of medical education occurs in various
social settings (small groups, large classes, clinical environments), it is
critical to examine how group members interact. One type of influence on these
interactions is conformity, whereby an individual changes his or her own
behaviour to match incorrect responses of others in a group. Conformity to peer
pressure has been replicated in experimental research conducted in many countries
over the last 60 years. There is newly emerging empirical evidence of this effect
in medical education, suggesting that subtle motivations and pressures within a
group may prevent students from challenging or questioning information that seems
incorrect. OBJECTIVES: This narrative review aims to present an overview of
theory and findings in research into conformity in the fields of social
psychology, business, sociology and aviation theory to demonstrate its direct
relevance to medical education and the health professions. METHODS: We searched
online databases (MEDLINE, PubMed, PsycINFO and ProQuest) from the University of
Calgary catalogue. We also searched citations in articles reviewed and references
provided by colleagues. We limited our narrative review to publications released
between 1950 and 2012. RESULTS: Group conformity behaviour may be one of a number
of communication challenges associated with interprofessional care, and may
represent a factor contributing to the burden of adverse events. This paper calls
for a new programme of research into conformity in medical education that
provides systematic empirical evidence of its relevance and applications in
education, health care and practice. CONCLUSIONS: This review reveals decades of
anecdotal and empirical evidence that conformity is a pervasive phenomenon across
disciplines. Further research is needed to elucidate which situations pose the
greatest risk for the occurrence of conformity, how to manage it in practice and
its implications for patient safety.
PMID- 25113113
TI - Overview of the world's medical schools: an update.
AB - CONTEXT: That few data are available on the characteristics of medical schools or
on trends within medical education internationally constitutes a major challenge
when developing strategies to address physician workforce shortages. Quality and
up-to-date information is needed to improve health and education policy planning.
METHODS: We used publicly available data from the International Medical Education
Directory and Avicenna Directories, and an internal education programme database
to gather data on medical education provision worldwide. We sent a semi
structured questionnaire to a selection of 346 medical schools, of which 218
(63%) in 81 different countries or territories replied. We contacted ministries
of health, national agencies for accreditation or similar bodies to clarify
inconsistencies among sources. We identified key informants to obtain country
level specific information. Descriptive statistics were used to analyse current
medical school data by country. RESULTS: There are about 2600 medical schools
worldwide. The countries with the largest numbers of schools are India (n = 304),
Brazil (n = 182), the USA (n = 173), China (n = 147) and Pakistan (n = 86). One
third of all medical schools are located in five countries and nearly half are
located in 10 countries. Of 207 independent states, 24 have no medical school and
50 have only one. Regionally, numbers of citizens per school differ: the
Caribbean region has one school per 0.6 million population; the Americas and
Oceania each have one school per 1.2 million population; Europe has one school
per 1.8 million population; Asia has one school per 3.5 million population, and
Africa has one school per 5.0 million population. In 2012, on average, there were
181 graduates per medical school. CONCLUSIONS: The total number and distribution
of medical schools around the world are not well matched with existing physician
numbers and distribution. The collection and aggregation of medical school data
are complex and would benefit from better information on local recognition
processes. Longitudinal comparisons are difficult and subject to several sources
of error. The consistency and quality of medical school data need to be improved
to accurately document potential supply; one example of such an advancement is
the World Directory of Medical Schools.
PMID- 25113114
TI - Key-feature questions for assessment of clinical reasoning: a literature review.
AB - OBJECTIVES: Key-feature questions (KFQs) have been developed to assess clinical
reasoning skills. The purpose of this paper is to review the published evidence
on the reliability and validity of KFQs to assess clinical reasoning. METHODS: A
literature review was conducted by searching MEDLINE (1946-2012) and EMBASE (1980
2012) via OVID and ERIC. The following search terms were used: key feature;
question or test or tests or testing or tested or exam; assess or evaluation, and
case-based or case-specific. Articles not in English were eliminated. RESULTS:
The literature search resulted in 560 articles. Duplicates were eliminated, as
were articles that were not relevant; nine articles that contained reliability or
validity data remained. A review of the references and of citations of these
articles resulted in an additional 12 articles to give a total of 21 for this
review. Format, language and scoring of KFQ examinations have been studied and
modified to maximise reliability. Internal consistency reliability has been
reported as being between 0.49 and 0.95. Face and content validity have been
shown to be moderate to high. Construct validity has been shown to be good using
vector thinking processes and novice versus expert paradigms, and to discriminate
between teaching methods. The very modest correlations between KFQ examinations
and more general knowledge-based examinations point to differing roles for each.
Importantly, the results of KFQ examinations have been shown to successfully
predict future physician performance, including patient outcomes. CONCLUSIONS:
Although it is inaccurate to conclude that any testing format is universally
reliable or valid, published research supports the use of examinations using KFQs
to assess clinical reasoning. The review identifies areas of further study,
including all categories of evidence. Investigation into how examinations using
KFQs integrate with other methods in a system of assessment is needed.
PMID- 25113115
TI - You've got to know the rules to play the game: how medical students negotiate the
hidden curriculum of surgical careers.
AB - OBJECTIVES: The hidden curriculum may be framed as the culture, beliefs and
behaviours of a community that are passed to students outside formal course
offerings. Medical careers involve diverse specialties, each with a different
culture, yet how medical students negotiate these cultures has not been fully
explored. Using surgery as a case study, we aimed to establish, first, whether a
specialty-specific hidden curriculum existed for students, and second, how
students encountered and negotiated surgical career options. METHODS: Using a
constructivist grounded theory approach, we explored students' thoughts, beliefs
and experiences regarding career decisions and surgery. An exploratory
questionnaire informed the discussion schedule for semi-structured individual
interviews. Medical students were purposively sampled by year group, gender and
career intentions in surgery. Data collection and analysis were iterative:
analysis followed each interview and guided the adaptation of our discussion
schedule to further our evolving model. RESULTS: Students held a clear sense of a
hidden curriculum in surgery. To successfully negotiate a surgical career,
students perceived that they must first build networks because careers
information flows through relationships. They subsequently enacted what they
learned by accruing the accolades ('ticking the boxes') and appropriating the
dispositions ('walking the talk') of 'future surgeons'. This allowed them to
identify themselves and to be identified by others as 'future surgeons' and to
gain access to participation in the surgical world. Participation then enabled
further network building and access to careers information in a positive feedback
loop. For some, negotiating the hidden curriculum was more difficult, which, for
them, rendered a surgical career unattractive or unattainable. CONCLUSIONS:
Students perceive a clear surgery-specific hidden curriculum. Using a
constructivist grounded theory approach, we have developed a model of how
students encounter, uncover and enact this hidden curriculum to succeed. Drawing
on concepts of Bourdieu, we discuss unequal access to the hidden curriculum,
which was found to exclude many from the possibility of a surgical career.
PMID- 25113116
TI - 'We' not 'I': health advocacy is a team sport.
AB - CONTEXT: Health advocacy, although recognised as a professional responsibility,
is often seen as overwhelming, perhaps because it is framed conceptually as an
activity that each physician should undertake alone rather than as a
collaborative process. In the context of a study exploring how effective
physician health advocates conceptualise their roles and their activities related
to health advocacy, we uncovered data that speak directly of the issue of whether
the activities of health advocates are enacted as individual or collective
pursuits. METHODS: We interviewed ten physicians, identified by others as
effective health advocates, regarding their advocacy activities. We collected and
analysed data in an iterative process, informed by constructivist grounded
theory, continuously refining the interview framework and examining evolving
themes. The final coding scheme was applied to all transcripts. RESULTS: Health
advocacy was viewed by these physicians as a collective activity. This collective
construction of advocacy presented in three ways: (i) as teamwork by
interprofessional teams of individuals with clearly defined roles and functional,
task-oriented goals; (ii) as a process involving networks of resources or people
that can be accessed for both support and reinforcement, and (iii) as a process
involving collaborative think-tanks in which members contribute different
perspectives to enact collective problem solving at a conceptual level.
CONCLUSIONS: Effective health advocates do not conceptualise themselves as stand
alone experts who must do everything themselves. Their collective approach makes
it possible for these physicians to incorporate health advocacy into their
clinical practice. However, although conceptualising health advocacy as a
collective activity may make it less daunting, this way of understanding health
advocacy is not compatible with current formal descriptions of the associated
competencies.
PMID- 25113117
TI - Feedback in action within bedside teaching encounters: a video ethnographic
study.
AB - CONTEXT: Feedback associated with teaching activities is often synonymous with
reflection on action, which comprises the evaluative assessment of performance
out of its original context. Feedback in action (as correction during clinical
encounters) is an underexplored, complementary resource facilitating students'
understanding and learning. OBJECTIVES: The purpose of this study was to explore
the interactional patterns and correction modalities utilised in feedback
sequences between doctors and students within general practice-based bedside
teaching encounters (BTEs). METHODS: A qualitative video ethnographic approach
was used. Participants were recorded in their natural settings to allow
interactional practices to be contextually explored. We examined 12 BTEs recorded
across four general practices and involving 12 patients, four general
practitioners and four medical students (209 minutes and 20 seconds of data)
taken from a larger corpus. Data analysis was facilitated by Transana video
analysis software and informed by previous conversation analysis research in
ordinary conversation, classrooms and health care settings. RESULTS: A range of
correction strategies across a spectrum of underlying explicitness were
identified. Correction strategies classified at extreme poles of this scale (high
or low explicitness) were believed to be less interactionally effective. For
example, those using abrupt closing of topics (high explicitness) or
interactional ambiguity (low explicitness) were thought to be less effective than
embedded correction strategies that enabled the student to reach the correct
answer with support. CONCLUSIONS: We believe that educators who are explicitly
taught linguistic strategies for how to manage feedback in BTEs might manage
learning more effectively. For example, clinicians might maximise learning
moments during BTEs by avoiding abrupt or ambiguous feedback practices. Embedded
correction strategies can enhance student participation by guiding students
towards the correct answer. Clinician corrections can sensitively manage student
face-saving by minimising the exposure of student error to patients. Furthermore,
we believe that the effective practices highlighted by our analysis might
facilitate successful transformation of feedback in action into feedback for
action.
PMID- 25113118
TI - Supervising incoming first-year residents: faculty expectations versus residents'
experiences.
AB - CONTEXT: First-year residents begin clinical practice in settings in which
attending staff and senior residents are available to supervise their work. There
is an expectation that, while being supervised and as they become more
experienced, residents will gradually take on more responsibilities and function
independently. OBJECTIVES: This study was conducted to define 'entrustable
professional activities' (EPAs) and determine the extent of agreement between the
level of supervision expected by clinical supervisors (CSs) and the level of
supervision reported by first-year residents. METHODS: Using a nominal group
technique, subject matter experts (SMEs) from multiple specialties defined EPAs
for incoming residents; these represented a set of activities to be performed
independently by residents by the end of the first year of residency, regardless
of specialty. We then surveyed CSs and first-year residents from one institution
in order to compare the levels of supervision expected and received during the
day and night for each EPA. RESULTS: The SMEs defined 10 EPAs (e.g. completing
admission orders, obtaining informed consent) that were ratified by a national
panel. A total of 113 CSs and 48 residents completed the survey. Clinical
supervisors had the same expectations regardless of time of day. For three EPAs
(managing i.v. fluids, obtaining informed consent, obtaining advanced directives)
the level of supervision reported by first-year residents was lower than that
expected by CSs (p < 0.001) regardless of time of day (i.e. day or night). For
four more EPAs (initiating the management of a critically ill patient, handing
over the care of a patient to colleagues, writing a discharge prescription,
coordinating a patient discharge) differences applied only to night-time work (p
<= 0.001). CONCLUSIONS: First-year residents reported performing EPAs with less
supervision than expected by CSs, especially during the night. Using EPAs to
guide the content of the undergraduate curriculum and during examinations could
help better align CSs' and residents' expectations about early residency
supervision.
PMID- 25113119
TI - What is the role of e-learning? Looking past the hype.
PMID- 25113120
TI - Correction of the Scimitar syndrome, a rare cardiac venous anomaly, leading to
Budd-Chiari syndrome: a case report.
AB - INTRODUCTION: Scimitar syndrome is a congenital heart disease characterized by an
abnormal drainage of the right lung into the inferior vena cava, the right atrium
or a variety of venous connections from the anomalous pulmonary vein to a
systemic vein. This left-to-right shunt induces pulmonary hypertension and is an
indication for surgical repair in cases of a history of recurrent pneumonia or
significant left-to-right shunting. A corrective approach, which consists of
rerouting the anomalous pulmonary flow to the left atrium, is usually performed.
Complications of scimitar repair are stenosis, thrombosis and occlusion of the
scimitar vein and its deviation. CASE PRESENTATION: This case report describes a
53-year-old Caucasian woman with known scimitar syndrome, undergoing surgical
repair due to invaliding symptoms of dyspnoea, and presenting with postoperative
Budd-Chiari syndrome due to anomalous drainage of her right hepatic vein into the
left atrium. It is an interesting cause of liver pathology caused by Budd-Chiari
that never has been described before. CONCLUSIONS: This case report emphasizes
the importance of a thorough preoperative evaluation, and the importance of
antecedents in newly presenting pathology. It is an interesting cause of a known
hepatic syndrome, the Budd-Chiari syndrome. This case report is of interest to
many specialties, including Hepatology, Cardiology, Radiology and Cardiovascular
Surgery. It exposes a new interesting anatomic variation of the scimitar syndrome
with significant postoperative implications.
PMID- 25113121
TI - Detection of antibodies against the CB9 to ICB10 region of merozoite surface
protein-1 of Plasmodium vivax among the inhabitants in epidemic areas.
AB - BACKGROUND: The purpose of this study was to examine the usefulness of the
conserved block 9 (CB9) to interspecies conserved block (ICB10) region of
Plasmodium vivax merozoite surface protein-1 (MSP-1 (ICB910)) as a serodiagnostic
tool for understanding malaria transmission. METHODS: Antibody titre in the blood
samples collected from the inhabitants of Gimpo city, Paju city and Yeoncheon
county of Gyeonggi Province, as well as Cheorwon county of Gangwon Province,
South Korea were determined by enzyme-linked immunosorbent assay (ELISA).
Microscopic examination was performed to identify malarial parasites. RESULTS:
MSP-1(ICB910) is encoded by a 1,212-bp sequence, which produced a recombinant
protein with a molecular weight of approximately 46 kDa. Antibody titres in 1,774
blood samples were determined with the help of ELISA using purified recombinant
MSP-1(ICB910). The overall ELISA-positive rate was 8.08% (n = 146). The annual
parasite incidences (APIs) in the regions where the blood sampling was carried
out gradually decreased from 2004 to 2005 (1.09 and 0.80, respectively).
Yeoncheon county had the highest ELISA-positive rate (10.20%, 46/451). Yeoncheon
county also had the highest API both in 2004 and 2005, followed by Cheorwon
county, Paju city and Gimpo city. CONCLUSIONS: The MSP-1 (ICB910)-ELISA-positive
rates were closely related to API in the geographic areas studied. These results
suggest that sero-epidemiological studies employing MSP-1 (ICB910)-ELISA may be
helpful in estimating the prevalence of malaria in certain geographic areas. MSP
1(ICB910)-ELISA can be effectively used to establish and evaluate malaria control
and eradication programmes in the affected areas.
PMID- 25113124
TI - Melatonin normalizes clinical and biochemical parameters of mild inflammation in
diet-induced metabolic syndrome in rats.
AB - The objective of this study was to evaluate the efficacy of melatonin to affect
mild inflammation in the metabolic syndrome (MS) induced by a high-fat diet in
rats. Adult Wistar male rats were divided into four groups (n = 16/group): (i)
control diet (3% fat); (ii) high-fat (35%) diet; (iii) high-fat diet + melatonin;
and (iv) melatonin. Rats had free access to high-fat or control chow and one of
the following drinking solutions for 10 wk: (a) tap water; (b) 25 MUg/mL of
melatonin. Plasma interleukin (IL)-1beta, IL-4, IL-6, IL-10, tumor necrosis
factor (TNF)-alpha, interferon (IFN)-gamma, and C-reactive protein (CRP) were
measured at two time intervals, that is, the middle of daylight period and the
middle of the scotophase. In addition, a number of somatic and metabolic
components employed clinically to monitor the MS were measured. Melatonin
decreased the augmented circulating levels of IL-1beta, IL-6, TNF-alpha, IFN
gamma, and CRP seen in obese rats and restored the depressed levels of IL-4 and
IL-10. Rats fed with the high-fat diet showed significantly higher body weights
and augmented systolic blood pressure from the third and fourth week onwards,
respectively, melatonin effectively preventing these changes. In high-fat-fed
rats, circulating low-density lipoprotein-cholesterol, total cholesterol, and
triglyceride concentration augmented significantly, melatonin being effective to
counteract these changes. Melatonin-treated rats showed a decreased insulin
resistance, the highest values of plasma high-density lipoprotein-cholesterol,
and the lowest values of plasma uric acid. The results indicate that melatonin is
able to normalize the altered biochemical pro-inflammatory profile seen in rats
fed with a high-fat diet.
PMID- 25113123
TI - Ammonium increases Ca(2+) signalling and up-regulates expression of TRPC1 gene in
astrocytes in primary cultures and in the in vivo brain.
AB - Rapid rise in ammonium concentration in the brain is the major pathogenic factor
in hepatic encephalopathy that is manifested by state of confusion, forgetfulness
and irritability, psychotic symptoms, delusions, lethargy, somnolence and, in the
terminal stages, coma. Primary cultures of mouse astrocytes were used to
investigate effects of chronic treatment (3 days) with ammonium chloride
(ammonium) at 3 mM, this being a relevant concentration for hepatic
encephalopathy condition, on metabotropic receptor agonist-induced increases in
free cytosolic Ca(2+) concentration [(Ca(2+))i], measured with fura-2 based
microfluorimetry and on store-operated Ca(2+) entry (SOCE) activated following
treatment with the SERCA inhibitor thapsigargin. The agonists used were the beta
adrenergic agonist isoproterenol, the alpha2-adrenergic agonist dexmedetomidine,
the InsP3 receptor (InsP3R) agonist adenophostin A and ryanodine receptor agonist
4-Chloro-m-cresol (4-CMC). Agonist-induced [Ca(2+)]i responses were significantly
increased in astrocytes chronically exposed to ammonium. Similarly, the SOCE,
meditated by the transient receptor potential channel 1 (TRPC1), was
significantly augmented. The ammonium-induced increase in SOCE was a result of an
up-regulation of mRNA and protein expression of TRPC1 in astrocytes. Increase in
TRPC1 expression and in SOCE were both prevented by ouabain antagonist canrenone.
Similar up-regulation of TRPC1 gene expression was found in the brain of adult
mice subjected to intraperitoneal injection of urease for 3 days. In transgenic
mice tagged with an astrocyte-specific or a neurone-specific markers and treated
with intraperitoneal injections of urease for 3 days, the fluorescence-activated
cell sorting of neurones and astrocytes demonstrated that TRPC1 mRNA expression
was up-regulated in astrocytes, but not in neurones.
PMID- 25113126
TI - Suppression of irrelevant activation in the horizontal and vertical Simon task
differs quantitatively not qualitatively.
AB - The Simon effect is usually explained by the assumption that the irrelevant
stimulus location automatically activates the corresponding response. In the case
of incongruent stimulus-response assignments automatically activated responses
therefore have to be suppressed to ensure correct responses. This account,
however, has been called into question for other than horizontally arranged
visual Simon tasks. We investigated whether there is a qualitative or
quantitative difference in suppression of irrelevant activation between
horizontally and vertically arranged Simon tasks, using delta-function analyses.
Sequential analyses revealed suppression after incongruent trials in both tasks,
supporting the idea of a quantitative rather than a qualitative difference
between the tasks. We conclude that automatic response activation is weaker in
vertical tasks resulting in lower inhibitory demands as compared to horizontal
tasks.
PMID- 25113122
TI - Why are astrocytes important?
AB - Astrocytes, which populate the grey and white mater of the brain and the spinal
cord are highly heterogeneous in their morphology and function. These cells are
primarily responsible for homeostasis of the central nervous system (CNS). Most
central synapses are surrounded by exceedingly thin astroglial perisynaptic
processes, which act as "astroglial cradle" critical for genesis, maturation and
maintenance of synaptic connectivity. The perisynaptic glial processes are
densely packed with numerous transporters, which provide for homeostasis of ions
and neurotransmitters in the synaptic cleft, for local metabolic support and for
release of astroglial derived scavengers of reactive oxygen species. Through
perivascular processes astrocytes contribute to blood-brain barrier and form
"glymphatic" drainage system of the CNS. Furthermore astrocytes are indispensible
for glutamatergic and gamma-aminobutyrate-ergic synaptic transmission being the
supplier of neurotransmitters precursor glutamine via an astrocytic/neuronal
cycle. Pathogenesis of many neurological disorders, including neuropsychiatric
and neurodegenerative diseases is defined by loss of homeostatic function
(astroglial asthenia) or remodelling of astroglial homoeostatic capabilities.
Astroglial cells further contribute to neuropathologies through mounting complex
defensive programme generally known as reactive astrogliosis.
PMID- 25113127
TI - The specificity of expertise: for whom is the clave pattern the "key" to salsa
music?
AB - Each Latin salsa music style is associated with a characteristic clave pattern
that constitutes an essential structure for performers. In this article we asked
what types of expertise are needed to detect the correct salsa-clave pairing.
Using two clave patterns (the 3-2 and 2-3 son clave) and three manipulated
alternatives, we asked listeners to choose the correct clave pattern for a
variety of bomba, calypso, mambo and merengue excerpts. The results of Studies 1
and 2 show that listeners unfamiliar with salsa were unable to detect the correct
salsa-clave pairing. Listeners who had some music training or were familiar with
salsa detected the need for syncopation but not the specific pairing. Only
musicians well-acquainted with salsa correctly detected the salsa-clave pairing.
Studies 3 and 4 showed that incorrect choices were not due to an inability to
distinguish between the alternatives: both adults and five-year-olds could easily
tell apart the various patterns we used. We conclude that the distinction between
the 2-3 and 3-2 claves is not inherent in the music itself, but rather is a
convention to be learned through exposure and training. We discuss the results
using an analogy to language learning.
PMID- 25113125
TI - Single adatom dynamics at monatomic steps of free-standing few-layer reduced
graphene.
AB - Steps and their associated adatoms extensively exist and play prominent roles in
affecting surface properties of materials. Such impacts should be especially
pronounced in two-dimensional, atomically-thin membranes like graphene. However,
how single adatom behaves at monatomic steps of few-layer graphene is still
illusive. Here, we report dynamics of individual adatom at monatomic steps of
free-standing few-layer reduced graphene under the electron beam radiations, and
demonstrate the prevalent existence of monatomic steps even down to unexpectedly
ultrasmall lateral size of a circular diameter of ~5 A. Single adatom prefers to
stay at the edges of the atomic steps of few-layer reduced graphene and evolve
with the steps. Moreover, we also find that how the single adatom behaves at
atomic step edges can be remarkably influenced by the type of adatoms and step
edges. Such single adatoms at monatomic steps and ultrasmall atomic steps open up
a new window for surface physics and chemistry for graphene-based as well as
other two-dimensional materials.
PMID- 25113128
TI - Know thy sound: perceiving self and others in musical contexts.
AB - This review article provides a summary of the findings from empirical studies
that investigated recognition of an action's agent by using music and/or other
auditory information. Embodied cognition accounts ground higher cognitive
functions in lower level sensorimotor functioning. Action simulation, the
recruitment of an observer's motor system and its neural substrates when
observing actions, has been proposed to be particularly potent for actions that
are self-produced. This review examines evidence for such claims from the music
domain. It covers studies in which trained or untrained individuals generated
and/or perceived (musical) sounds, and were subsequently asked to identify who
was the author of the sounds (e.g., the self or another individual) in immediate
(online) or delayed (offline) research designs. The review is structured
according to the complexity of auditory-motor information available and includes
sections on: 1) simple auditory information (e.g., clapping, piano, drum sounds),
2) complex instrumental sound sequences (e.g., piano/organ performances), and 3)
musical information embedded within audiovisual performance contexts, when action
sequences are both viewed as movements and/or listened to in synchrony with
sounds (e.g., conductors' gestures, dance). This work has proven to be
informative in unraveling the links between perceptual-motor processes,
supporting embodied accounts of human cognition that address action observation.
The reported findings are examined in relation to cues that contribute to agency
judgments, and their implications for research concerning action understanding
and applied musical practice.
PMID- 25113129
TI - Emotion modulates allocentric but not egocentric stimulus localization:
implications for dual visual systems perspectives.
AB - Considerable evidence suggests that emotional cues influence processing
prioritization and neural representations of stimuli. Specifically, within the
visual domain, emotion is known to impact ventral stream processes and ventral
stream-mediated behaviours; it remains unclear, however, the extent to which
emotion impacts dorsal stream processes. In the present study, participants
localized a visual target stimulus embedded within a background array utilizing
allocentric localization (requiring an object-centred representation of visual
space to perform an action) and egocentric localization (requiring purely target
directed actions), which are thought to differentially rely on the ventral versus
dorsal visual stream, respectively. Simultaneously, a task-irrelevant negative,
positive or neutral sound was presented to produce an emotional context. In line
with predictions, we found that during allocentric localization, response
accuracy was enhanced in the context of negative compared to either neutral or
positive sounds. In contrast, no significant effects of emotion were identified
during egocentric localization. These results raise the possibility that negative
emotional auditory contexts enhance ventral stream, but not dorsal stream,
processing in the visual domain. Furthermore, this study highlights the
complexity of emotion-cognition interactions, indicating how emotion can have a
differential impact on almost identical overt behaviours that may be governed by
distinct neurocognitive systems.
PMID- 25113130
TI - Do the same genes underlie parallel phenotypic divergence in different Littorina
saxatilis populations?
AB - Parallel patterns of adaptive divergence and speciation are cited as powerful
evidence for the role of selection driving these processes. However, it is often
not clear whether parallel phenotypic divergence is underlain by parallel genetic
changes. Here, we asked about the genetic basis of parallel divergence in the
marine snail Littorina saxatilis, which has repeatedly evolved coexisting
ecotypes adapted to either crab predation or wave action. We sequenced the
transcriptome of snails of both ecotypes from three distant geographical
locations (Spain, Sweden and United Kingdom) and mapped the reads to the L.
saxatilis reference genome. We identified genomic regions potentially under
divergent selection between ecotypes within each country, using an outlier
approach based on F(ST) values calculated per locus. In line with previous
studies indicating that gene reuse is generally common, we expected to find
extensive sharing of outlier loci due to recent shared ancestry and gene flow
between at least two of the locations in our study system. Contrary to our
expectations, we found that most outliers were country specific, suggesting that
much of the genetic basis of divergence is not shared among locations. However,
we did find that more outliers were shared than expected by chance and that
differentiation of shared outliers is often generated by the same SNPs. We
discuss two mechanisms potentially explaining the limited amount of sharing we
observed. First, a polygenic basis of divergent traits might allow for multiple
distinct molecular mechanisms generating the same phenotypic patterns. Second,
additional, location-specific axes of selection that we did not focus on in this
study may produce distinct patterns of genetic divergence within each site.
PMID- 25113131
TI - Very low rates of screening for metabolic syndrome among patients with severe
mental illness in Durban, South Africa.
AB - BACKGROUND: Sub Saharan African is experiencing the largest increase in the
prevalence of type 2 diabetes mellitus and cardiovascular disease globally.
Metabolic syndrome (MetS) is a cluster of risk factors for these conditions.
There is a consistently higher prevalence of cardiometabolic disease among
individuals with severe mental illness (SMI) compared to the general population
worldwide. However, it is known from research in high income countries that
screening for MetS in patients with SMI is low. The objective of this study was
to document the extent of the expected low frequency of testing for all the
components of the metabolic syndrome (MetS) in patients with SMI in a low middle
income country. METHODS: This was a cross sectional study, undertaken from
January to June 2012 on out-patients with SMI who were treated with antipsychotic
medication for at least 6 months. The study measured the proportion of
participants who were tested for MetS in the previous year. RESULTS: The study
included 331 (M: F; 167:164) participants with a mean age of 35.2 +/- 11.98
years. The majority (78.8%) were black South Africans. Only 2 subjects (0.6%)
were screened for all five components of MetS. Regarding the individual
components, 99%, 0.6%, 3.9% and 1.8% were screened for raised blood pressure,
abdominal obesity, hyperglycaemia, hypertriglyceridaemia and decreased high
density lipoprotein cholesterol respectively. CONCLUSION: It is unacceptable that
less than one percent of our participants were adequately screened for modifiable
risk factors for type 2 diabetes mellitus and cardiovascular disease which are
the most common causes of mortality among patients with SMI. These results
highlight the need for translating guidelines into action in low and middle
income countries.
PMID- 25113132
TI - Incidence and correlates of hepatitis C virus infection in a large cohort of
prisoners who have injected drugs.
AB - BACKGROUND: Hepatitis C virus (HCV) infection is common among prisoners,
particularly those with a history of injecting drug use (IDU). Incarcerated
people who inject drugs frequently report high-risk injecting practices both in
prison and in the community. In spite of rising morbidity and mortality,
utilisation of HCV-related services in Australia has been persistently low. This
study aimed to describe the incidence, prevalence and correlates of HCV
seropositivity in a large cohort of prisoners who have injected drugs, and to
identify correlates of receiving confirmation of active infection. METHODS: Data
linkage to a State-wide statutory notifiable diseases surveillance system was
used to investigate the incidence of notified HCV seropositivity, seroconversion
and confirmed HCV infection in a cohort of 735 prisoners with a history of IDU,
over 14 years of follow up. Hepatitis C test results from prison medical records
were used to identify correlates of testing positive in prison. RESULTS: The
crude incidence of HCV notification was 5.1 cases per 100 person-years. By the
end of follow up, 55.1% of the cohort had been the subject of a HCV-related
notification, and 47.4% of those tested in prison were HCV seropositive. In
multivariable analyses, injecting in prison was strongly associated with HCV
seropositivity, as was opioid use compared to injection of other drugs. The rate
of reported diagnostic confirmation among those with notified infections was very
low, at 6.6 confirmations per 100 seropositive participants per year.
CONCLUSIONS: Injecting drugs in prison was strongly associated with HCV
seropositivity, highlighting the need for increased provision of services to
mitigate the risk of transmission within prisons. Once identified as seropositive
through screening, people with a history of IDU and incarceration may not be
promptly receiving diagnostic services, which are necessary if they are to access
treatment. Improving access to HCV-related services will be of particular
importance in the coming years, as HCV-related morbidity and mortality is
increasing, and next generation therapies are becoming more widely available.
PMID- 25113133
TI - The antidiabetic agent glibenclamide protects airway hyperresponsiveness and
inflammation in mice.
AB - Glibenclamide has a newly discovered role in inflammation regulation besides its
antidiabetic effect. As an inhibitor of ATP-sensitive potassium (KATP) channel,
glibenclamide antagonizes the relaxation of the tracheal smooth muscle. This
indicates that glibenclamide might attenuate airway inflammation while aggravate
airway hyperresponsiveness (AHR) in asthmatics. Clinically, many diabetics with
asthma are prescribed with glibenclamide to control blood glucose. However,
whether glibenclamide could exert any effects on asthmatic inflammation remains
unknown. Using an ovalbumin (OVA)-induced mouse model of asthma, we evaluated the
effects of glibenclamide on the AHR and inflammation. Interestingly,
glibenclamide reduced all the cardinal features of asthma in OVA-challenged mice,
including AHR, airway inflammation, and T-helper type 2 (Th2) cytokines.
Glibenclamide also downregulated OVA-induced expressions of vascular cell
adhesion molecule 1 (VCAM-1) and phosphorylated signal transducer and activator
of transcription 6 (p-STAT6) in the lung. In addition, increased sulfonylurea
receptor 1 (SUR1) expression in the lung was observed after the OVA challenge.
These findings suggest that the classic sulfonylurea glibenclamide plays an
important protective role in the development of asthma, which not only provides
the evidence for the safety of prescribed glibenclamide in diabetics combined
with asthma but also indicates a possible new therapeutic for asthma via
targeting glibenclamide-related pathways.
PMID- 25113134
TI - Human leukocyte antigen DR surface expression on CD14+ monocytes during adverse
events after hematopoietic stem cell transplantation.
AB - The human leukocyte antigen DR surface expression on CD14+ monocytes reflects the
degree to which these cells have been activated. Given the central role monocytes
and macrophages play in the immune system, a decreased human leukocyte antigen DR
expression on CD14+ monocytes results in a hallmark of altered immune status
during systemic inflammatory response syndrome. We hypothesize that human
leukocyte antigen DR expression might be similarly altered after hematopoietic
stem cell transplantation and during post-transplant complications. Using flow
cytometry, this study investigates the human leukocyte antigen DR surface
expression of CD14+ monocytes in 30 pediatric and young adult patients up to 1
year after hematopoietic stem cell transplantation. Normal values were derived
from a control group of healthy children, adolescents, and young adults. Human
leukocyte antigen DR expression decreased significantly prior and during
bacterial infection or sepsis. By contrast, human leukocyte antigen DR expression
levels were elevated before and at the time of viremia. Human leukocyte antigen
DR expression was also elevated during acute graft-versus-host disease. In
contrast, the expression was reduced when patients had hepatic veno-occlusive
disease. A significant decrease of human leukocyte antigen DR expression was
associated with a relapse of the underlying disease and before death. Human
leukocyte antigen DR expression on CD14+ monocytes appears to be a promising
parameter that might allow identification of patients at risk after hematopoietic
stem cell transplantation.
PMID- 25113135
TI - An automatic patient-specific seizure onset detection method using intracranial
electroencephalography.
AB - OBJECTIVE: This study presents a multichannel patient-specific seizure detection
method based on the empirical mode decomposition (EMD) and support vector machine
(SVM) classifier. MATERIALS AND METHODS: The EMD is used to extract features from
intracranial electroencephalography (EEG). A machine-learning algorithm is used
as a classifier to discriminate between seizure and nonseizure intracranial EEG
epochs. A postprocessing algorithm is proposed to reject artifacts and increase
the robustness of the method. The proposed method was evaluated using 463 hours
of intracranial EEG recordings from 17 patients with a total of 51 seizures in
the Freiburg EEG database. RESULTS: The proposed method had better performance
than most of the existing seizure detection systems, including an average
sensitivity of 92%, false detection rate (FDR) of 0.17/hour, and time delay (TD)
of 12 sec. Moreover, the FDR could be further reduced by a TD extension.
CONCLUSIONS: Given its high sensitivity and low FDR, the proposed patient
specific seizure detection method can greatly assist clinical staff with
automatically marking seizures in long-term EEG or detecting seizure onset online
with high performance. Early and accurate seizure detection using this method may
serve as a practical tool for planning epilepsy interventions.
PMID- 25113137
TI - Metastable ionic diodes derived from an amine-based polymer of intrinsic
microporosity.
AB - A highly rigid amine-based polymer of intrinsic microporosity (PIM), prepared by
a polymerization reaction involving the formation of Troger's base, is
demonstrated to act as an ionic diode with electrolyte-dependent bistable
switchable states.
PMID- 25113136
TI - Effects of sigh during pressure control and pressure support ventilation in
pulmonary and extrapulmonary mild acute lung injury.
AB - INTRODUCTION: Sigh improves oxygenation and lung mechanics during pressure
control ventilation (PCV) and pressure support ventilation (PSV) in patients with
acute respiratory distress syndrome. However, so far, no study has evaluated the
biological impact of sigh during PCV or PSV on the lung and distal organs in
experimental pulmonary (p) and extrapulmonary (exp) mild acute lung injury (ALI).
METHODS: In 48 Wistar rats, ALI was induced by Escherichia coli
lipopolysaccharide either intratracheally (ALIp) or intraperitoneally (ALIexp).
After 24 hours, animals were anesthetized and mechanically ventilated with PCV or
PSV with a tidal volume of 6 mL/kg, FiO2 = 0.4, and PEEP = 5 cmH2O for 1 hour.
Both ventilator strategies were then randomly assigned to receive periodic sighs
(10 sighs/hour, Sigh) or not (non-Sigh, NS). Ventilatory and mechanical
parameters, arterial blood gases, lung histology, interleukin (IL)-1beta, IL-6,
caspase-3, and type III procollagen (PCIII) mRNA expression in lung tissue, and
number of apoptotic cells in lung, liver, and kidney specimens were analyzed.
RESULTS: In both ALI etiologies: (1) PCV-Sigh and PSV-Sigh reduced transpulmonary
pressure, and (2) PSV-Sigh reduced the respiratory drive compared to PSV-NS. In
ALIp: (1) PCV-Sigh and PSV-Sigh decreased alveolar collapse as well as IL-1beta,
IL-6, caspase-3, and PCIII expressions in lung tissue, (2) PCV-Sigh increased
alveolar-capillary membrane and endothelial cell damage, and (3) abnormal
myofibril with Z-disk edema was greater in PCV-NS than PSV-NS. In ALIexp: (1) PSV
Sigh reduced alveolar collapse, but led to damage to alveolar-capillary membrane,
as well as type II epithelial and endothelial cells, (2) PCV-Sigh and PSV-Sigh
increased IL-1beta, IL-6, caspase-3, and PCIII expressions, and (3) PCV-Sigh
increased the number of apoptotic cells in the lung compared to PCV-NS.
CONCLUSIONS: In these models of mild ALIp and ALIexp, sigh reduced alveolar
collapse and transpulmonary pressures during both PCV and PSV; however, improved
lung protection only during PSV in ALIp.
PMID- 25113138
TI - Increasing childhood influenza vaccination: a cluster randomized trial.
AB - BACKGROUND: Since the 2008 inception of universal childhood influenza
vaccination, national rates have risen more dramatically among younger children
than older children and reported rates across racial/ethnic groups are
inconsistent. Interventions may be needed to address age and racial disparities
to achieve the recommended childhood influenza vaccination target of 70%.
PURPOSE: To evaluate an intervention to increase childhood influenza vaccination
across age and racial groups. METHODS: In 2011-2012, a total of 20 primary care
practices treating children were randomly assigned to the intervention and
control arms of a cluster randomized controlled trial to increase childhood
influenza vaccination uptake using a toolkit and other strategies including early
delivery of donated vaccine, in-service staff meetings, and publicity. RESULTS:
The average vaccination differences from pre-intervention to the intervention
year were significantly larger in the intervention arm (n=10 practices) than the
control arm (n=10 practices); for children aged 9-18 years (11.1 pct pts
intervention vs 4.3 pct pts control, p<0.05); for non-white children (16.7 pct
pts intervention vs 4.6 pct pts control, p<0.001); and overall (9.9 pct pts
intervention vs 4.2 pct pts control, p<0.01). In multi-level modeling that
accounted for person- and practice-level variables and the interactions among
age, race, and intervention, the likelihood of vaccination increased with younger
age group (6-23 months); white race; commercial insurance; the practice's pre
intervention vaccination rate; and being in the intervention arm. Estimates of
the interaction terms indicated that the intervention increased the likelihood of
vaccination for non-white children in all age groups and white children aged 9-18
years. CONCLUSIONS: A multi-strategy intervention that includes a practice
improvement toolkit can significantly improve influenza vaccination uptake across
age and racial groups without targeting specific groups, especially in practices
with large percentages of minority children.
PMID- 25113139
TI - Motivational counseling to reduce sitting time: a community-based randomized
controlled trial in adults.
AB - BACKGROUND: Sedentary behavior is regarded as a distinct risk factor for
cardiometabolic morbidity and mortality, but knowledge of the efficacy of
interventions targeting reductions in sedentary behavior is limited. PURPOSE: To
investigate the effect of an individualized face-to-face motivational counseling
intervention aimed at reducing sitting time. DESIGN: A randomized, controlled,
observer-blinded, community-based trial with two parallel groups using open-end
randomization with 1:1 allocation. SETTING/PARTICIPANTS: A total of 166 sedentary
adults were consecutively recruited from the population-based Health2010 Study.
INTERVENTION: Participants were randomized to a control (usual lifestyle) or
intervention group with four individual theory-based counseling sessions. MAIN
OUTCOME MEASURES: Objectively measured overall sitting time (ActivPAL 3TM, 7
days); secondary measures were breaks in sitting time, anthropometric measures,
and cardiometabolic biomarkers, assessed at baseline and after 6 months. Data
were collected in 2010-2012 and analyzed in 2013-2014 using repeated measures
multiple regression analyses. RESULTS: Ninety-three participants were randomized
to the intervention group and 73 to the control group, and 149 completed the
study. The intervention group had a mean sitting time decrease of -0.27
hours/day, corresponding to 2.9% of baseline sitting time (hours/day); the
control group increased mean sitting time by 0.06 hours/day. The between-group
difference in change, -0.32 hours/day (95% CI=-0.87, 0.24, p=0.26), was not
statistically significant. Significant differences in change in fasting serum
insulin of -5.9 pmol/L (95% CI=-11.4, -0.5, p=0.03); homeostasis model assessment
estimated insulin resistance of -0.28 (95% CI=-0.53, -0.03, p=0.03); and waist
circumference of -1.42 cm (95% CI=-2.54, -0.29, p=0.01) were observed in favor of
the intervention group. CONCLUSIONS: Although the observed decrease in sitting
time was not significant, a community-based, individually tailored, theory-based
intervention program aimed at reducing sitting time may be effective for
increasing standing and improving cardiometabolic health in sedentary adults.
TRIAL REGISTRATION: This study is registered at Clinicaltrials.gov (NCT00289237).
PMID- 25113141
TI - FDA allows second experimental drug to be tested in Ebola patients.
PMID- 25113140
TI - Oestradiol modulates the effects of leptin on energy homeostasis by
corticotrophin-releasing factor type 2 receptor.
AB - In addition to its action in the control of the hypothalamic-pituitary-adrenal
axis, corticotrophin-releasing factor (CRF) has been described as an anorexigenic
neuropeptide, modulating food intake and energy expenditure. CRF synthesis is
influenced by leptin, which would act to increase CRF neurone activation in the
paraventricular nucleus (PVN). Gonadal hormones also participate in the
regulation of energy homeostasis. The reduction of food intake and body weight
gain in ovariectomised (OVX) rats treated with oestradiol is associated with an
increase in CRF mRNA expression in the PVN. The present study aimed to
investigate the role of CRF as a mediator of leptin responsiveness in the
presence of oestradiol. Wistar female rats were bilaterally OVX and divided into
three groups: OVX, OVX+E (i.e. treated with oestradiol) and OVX+PF (i.e. OVX
pairfed with OVX+E). The rats received daily s.c. injections of either oestradiol
cypionate or vehicle for 8 days. To evaluate the role of CRF on the effects of
leptin, we performed an i.c.v. leptin injection (10 MUg/5 MUl) with or without
previous i.c.v. treatment with an CRF-R2 antagonist. We observed that oestradiol
replacement in OVX rats reduced body weight gain and food intake. The effects of
exogenous leptin administration with respect to decreasing food intake and body
weight, and increasing uncoupling protein-1 expression in the brown adipose
tissue and neuronal activation in the arcuate nucleus, were reversed by previous
administration of a CRF-R2 antagonist only in oestradiol-treated OVX rats. These
effects appear to be mediated by CRF-2 receptor because the antagonist of this
receptor reversed the action of oestradiol on the effects of leptin.
PMID- 25113142
TI - Epithelial-mesenchymal transition as a fundamental underlying pathogenic process
in COPD airways: fibrosis, remodeling and cancer.
AB - Chronic obstructive pulmonary disease (COPD) is a complex condition, frequently
with a mix of airway and lung parenchymal damage. However, the earliest changes
are in the small airways, where most of the airflow limitation occurs. The
pathology of small airway damage seems to be wall fibrosis and obliteration, but
the whole airway is involved in a 'field effect'. Our novel observations on
active epithelial-mesenchymal transition (EMT) in the airways of smokers,
particularly in those with COPD, are changing the understanding of this airway
pathology and the aetiology of COPD. EMT involves a cascade of regulatory changes
that destabilise the epithelium with a motile and mesenchymal epithelial cell
phenotype emerging. One important manifestation of EMT activity involves up
regulation of specific key transcription factors (TFs), such as Smads, Twist, and
beta-catenin. Such TFs can be used as EMT biomarkers, in recognisable patterns
reflecting the potential major drivers of the process; for example, TGFbeta, Wnt,
and integrin-linked kinase systems. Thus, understanding the relative changes in
TF activity during EMT may provide rich information on the mechanisms driving
this whole process, and how they may change over time and with therapy. We have
sought to review the current literature on EMT and the relative expression of
specific TF activity, to define the networks likely to be involved in a similar
process in the airways of patients with smoking-related COPD.
PMID- 25113143
TI - A novel KIR2DL3 variant allele, KIR2DL3*031, identified from a southern Chinese
Han individual.
AB - The novel KIR2DL3*031 allele differs from KIR2DL3*00101 by a synonymous mutation
and a non-synonymous mutation.
PMID- 25113144
TI - Spontaneous passage of a very large ureteral stone.
PMID- 25113145
TI - Evaluation of antimicrobial treatment in a bovine model of acute Chlamydia
psittaci infection: tetracycline versus tetracycline plus rifampicin.
AB - Antimicrobial treatment of chlamydial infections is known to be of limited
efficacy. In this study, effects of doxycycline (D), usually the drug of choice,
were compared with the combined therapy of doxycycline and rifampicin (R) in a
bovine model of respiratory Chlamydia psittaci infection. After intrabronchial
inoculation of the pathogen, 30 animals were assigned to five groups (n = 6 per
group): untreated controls, monotherapy with D (5 mg kg(-1)day(-1) or 10 mg kg(
1)day(-1)), and combination therapy of D and R (600 mg day(-1)). Treatment
continued until day 14 post inoculation (d.p.i.). Clinical signs, inflammatory
markers, and pathological findings confirmed successful infection in all animals.
Reisolation of the pathogen was possible in 4/6 untreated animals and in 4/12
animals treated with D alone until 4 d.p.i., but in none of the calves of the two
D + R groups. Pathogen detection was possible in all animals without significant
differences among groups. Severity of disease and time course of its resolution,
assessed by clinical and pathological findings as well as inflammatory
parameters, were not significantly different between untreated controls and
calves receiving D alone or in combination with R. Regardless of the treatment
regimen, all groups recovered clinically and cleared the infection within 2
weeks.
PMID- 25113146
TI - Optimization of culturing conditions for toxicity testing with the alga Oophila
sp. (Chlorophyceae), an amphibian endosymbiont.
AB - Eggs of the yellow-spotted salamander (Ambystoma maculatum) have a symbiotic
relationship with green algae. It has been suggested that contaminants that are
preferentially toxic to algae, such as herbicides, may impair the symbiont and,
hence, indirectly affect the development of the salamander embryo. To enable
testing under near-standard conditions for first-tier toxicity screening, the
authors isolated the alga from field-collected eggs and identified conditions
providing exponential growth rates in the apparent asexual phase of the alga.
This approach provided a uniform, single-species culture, facilitating assessment
of common toxicity end points and comparison of sensitivity relative to other
species. Sequencing of the 18s ribosomal DNA indicated that the isolated alga is
closely related to the recently described Oophila amblystomatis but is more
similar to other known Chlamydomonas species, suggesting possible biogeographical
variability in the genetic identity of the algal symbiont. After a tiered
approach to culturing method refinement, a modified Bristol's media with 1 mM NH4
(+) as nitrogen source was found to provide suitable conditions for toxicity
testing at 18 degrees C and 200 umol m(-2) s(-1) photosynthetically active
radiation (PAR) on a 24-h light cycle. The validity of the approach was
demonstrated with Zn(2+) as a reference toxicant. Overall, the present study
shows that screening for direct effects of contaminants on the algal symbiont
without the presence of the host salamander is possible under certain laboratory
conditions.
PMID- 25113147
TI - Mother-child interactions in the NICU: relevance and implications for later
parenting.
AB - OBJECTIVE: This study examined the feasibility of observing mother-child
interactions in the neonatal intensive care unit (NICU), whether NICU
interactions related to later interactions, and how interactions related to child
and maternal characteristics. METHODS: The sample included 130 preterm infants
and their mothers, observed in a feeding interaction in the NICU. Dyads were
observed through 36 months postterm. RESULTS: Observed maternal positive
affective involvement and verbalizations in the NICU were associated with the
same parenting behaviors at 24 months, social support, socioeconomic status, and
being born in the late preterm period. Maternal negative affect and behavior were
unrelated to later maternal negativity or child and maternal characteristics.
CONCLUSIONS: Positive parenting assessed in the NICU appears related to later
parenting interaction quality, suggesting early assessment is possible. Maternal
negative affect and behavior toward children may not consistently emerge until
later in development.
PMID- 25113148
TI - Evaluation of regional cerebral glucose metabolism in patients with malignant
lymphoma of the body using statistical image analysis.
AB - OBJECTIVES: The aim of this study was to clarify the characteristics of regional
cerebral glucose metabolic abnormalities in patients with malignant lymphoma of
the body using statistical image analyses. Post-therapeutic changes in cerebral
glucose metabolism were also evaluated. METHODS: The subjects consisted of 30
patients, including 16 patients with diffuse large B-cell lymphoma and 14
patients with other types of lymphoma. Patients with primary cerebral lymphoma
were excluded from this study. All patients underwent CT and whole-body FDG-PET
scans, including 4-min brain scans using a dedicated PET/CT scanner during both
the pre- and post-treatment periods. The whole-body scans started 60 min after
the administration of 185 MBq of FDG, after which the brain data were extracted
from whole-body data. The degree of regional cerebral glucose metabolism was
evaluated on a voxel-by-voxel basis using statistical parametric mapping (SPM).
The total tumor glycolytic volume of the body was measured using a separate
workstation. The normal control subjects were 12 persons who underwent medical
check with FDG-PET/CT and had no lesions suggesting malignant tumor. RESULTS: The
level of regional cerebral glucose metabolism decreased in association with an
increase in the total glycolytic volume in the bilateral frontal and parietal
cortices. After chemotherapy, the statistical image analysis demonstrated an
interval recovery of the cerebral glucose metabolism of the bilateral parietal
and occipital cortices in the good responders, whereas there were no significant
differences observed in regional cerebral glucose metabolism between the pre- and
post-treatment images in the poor responders. Comparison between normal control
subjects and patients with pre-treatment lymphoma also showed that the regional
cerebral glucose metabolism decreased in the parieto-occipital cortices in
patients with lymphoma compared to normal control subjects. CONCLUSIONS: We
demonstrated that patients with malignant lymphoma of the body exhibited abnormal
regional cerebral glucose metabolism, which improves after chemotherapy. Although
the mechanism underlying the reduction of cerebral glucose metabolism remains
unclear, our findings indicate the functional alternation and/or subclinical
damage of the brain in patients with malignant lymphoma.
PMID- 25113149
TI - Nuclear medicine practice in Japan: a report of the seventh nationwide survey in
2012.
AB - OBJECTIVE: The Subcommittee on the Survey of Nuclear Medical Practice in Japan
has performed a nationwide survey of nuclear medicine practice every 5 years
since 1982 to survey contemporary nuclear medicine practice and its changes over
the years. METHODS: The subcommittee sent questionnaires, including the number
and category of examinations as well as the kind and dose of the
radiopharmaceuticals during the 30 days of June 2012, to all the nuclear medicine
institutes. The total numbers for the year 2012 were then estimated. RESULTS: A
total of 1,167 institutes responded to the survey, including the 14 in vitro
assay institutes and 266 PET centers. The recovery rate was 92 %. The number of
gamma cameras installed was 1,425 in total, with 9 % decrease in 5 years. Dual
head cameras and hybrid SPECT/CT scanners accounted for 84 and 10.5 %,
respectively. The number of single-photon tracer studies in 2012 was 1.15 million
which means decrease in 19 % in 5 years and 29 % in 10 years. All but cerebral
perfusion study and sentinel lymphoscintigraphy have decreased. Bone scintigraphy
was a leading examination (38.7 %), followed by cardiac studies (29.4 %) and
cerebral perfusion study (18.5 %) in order. SPECT studies showed an increase from
42.3 to 47.2 %. PET centers have also increased from 212 to 295, as compared to
the last survey. The 135 PET centers have installed one or two in-house
cyclotrons. PET studies showed 25.5 % increase in 5 years, with oncology
accounting for 96.3 %. (18)F-FDG accounted for 98.2 % (505,990 examinations). PET
examinations using (11)C-methionine have been increasing, with 3,352 examinations
in 2012. The number of new PET studies using (11)C-PIB PET was 695. (131)I
radioiodine targeted therapies showed an increase, including 3,644 patients (53.6
%) for thyroid cancer and 4,889 patients (17.9 %) for hyperthyroidism. Out
patient thyroid bed ablation therapy with 30 mCi of (131)I accounted for 21.0 %
of cancer patients. The number of admission rooms decreased from 158 to 135 in 5
years. In vitro radioassays have been declining continuously since 1992, with the
number of studies of 9.0 million in 2012. CONCLUSIONS: Single-photon examinations
showed a continuous tendency toward a decline in the survey. In contrast, the
number of hybrid SPECT/CT scanner examinations has increased. PET/CT study in the
oncology field and radionuclide targeted therapy have steadily increased.
PMID- 25113151
TI - One-year outcomes associated with using observation services in triaging patients
with nonspecific chest pain.
AB - BACKGROUND: Observation services are provided in greatly variant settings. The
aim of this study was to reexamine the effectiveness of observation services
compared to inpatient units for patients with nonspecific chest pain. HYPOTHESIS:
Patients admitted to observation units have similar outcomes to patients admitted
to inpatient wards. METHODS: We conducted a claim-based retrospective study for
7549 patients who were admitted to observation and inpatient units. Both models
of care were evaluated using the 1-year costs related to chest
pain/cardiovascular diseases, and primary and secondary outcomes. Primary outcome
was a composite of myocardial infarction, congestive heart failure, stroke, or
cardiac arrest, whereas secondary outcomes included revascularization procedures,
emergency room revisits, and hospitalization due to cardiovascular diseases.
RESULTS: Two-thirds (65.7%, n = 4962) of patients in the sample had observation
services, and 34.3% (n = 2587) were admitted to inpatient care. Of the inpatient
group, 4.9% experienced a total of 167 primary outcomes, whereas 14.1%
experienced a total of 571 secondary outcomes. In comparison, 3.8% of the
observation group experienced 238 primary outcomes, and 10.3% experienced 737
secondary outcomes. After adjusting for baseline characteristics using Cox
proportional hazard and quantile regression models, no differences between the 2
groups were detected in the 1-year costs of cardiovascular services and primary
or secondary outcomes. Patients who had observation services were 79% (95%
confidence interval: 1.24-2.58) more likely to have revascularization procedures
compared to those admitted to inpatient care. CONCLUSIONS: Patients who had
observation services had similar outcomes and 1-year costs compared to patients
admitted to inpatient wards.
PMID- 25113150
TI - UTIs in patients with neurogenic bladder.
AB - Urinary tract infections (UTI) remain one of the most prevalent and frustrating
morbidities for neurogenic bladder patients, and death attributed to urosepsis in
the spinal cord injury (SCI) patient is higher when compared to the general
population. Risk factors include urinary stasis, high bladder pressures, bladder
stones, and catheter use. While classic symptoms of UTI include dysuria,
increased frequency and urgency, neurogenic bladder patients present differently
with increased spasticity, autonomic dysreflexia, urinary incontinence, and vague
pains. Multiple modalities have been assessed for prevention including catheter
type, oral supplements, bladder irrigation, detrusor injections and prophylactic
antimicrobials. Of these, bladder inoculation with E. coli HU2117, irrigation
with iAluRil((r)), detrusor injections, and weekly prophylaxis with alternating
antibiotics appear to have a positive reduction in UTI but require further study.
Ultimately, treatment for symptomatic UTI should account for the varied flora and
possible antibiotic resistances including relying on urine cultures to guide
antibiotic therapy.
PMID- 25113153
TI - Representing and decomposing neural potential signals.
AB - This paper reviews methodologies for analyzing neural potentials via frequency,
time-frequency, or wavelet representations, and adaptive models that estimate the
signal's spatial or temporal structure. The fundamental assumptions of each
method are discussed. In particular, the Fourier transform is contrasted with
overcomplete representations, which are able to precisely delineate the timing
and/or frequency of neural events. Finally, a novel approach that combines
overcomplete representations with adaptive signal models is presented. This
approach describes a continuous signal as a linear combination of reoccurring
waveforms, referred to as phasic events, which are often associated with neural
processing. The new methodology automatically learns the reoccurring waveforms
and quantifies the neural potentials by the set of amplitudes and timings.
PMID- 25113152
TI - Health-related media use among youth audiences in Senegal.
AB - Lower- and middle-income countries (LMICs) are experiencing rapid changes in
access to and use of new internet and digital media technologies. The purpose of
this study was to better understand how younger audiences are navigating
traditional and newer forms of media technologies, with particular emphasis on
the skills and competencies needed to obtain, evaluate and apply health-related
information, also defined as health and media literacy. Sixteen focus group
discussions were conducted throughout Senegal in September 2012 with youth aged
15-25. Using an iterative coding process based on grounded theory, four themes
emerged related to media use for health information among Senegalese youth. They
include the following: (i) media utilization; (ii) barriers and conflicts
regarding media utilization; (iii) uses and gratifications and (iv) health and
media literacy. Findings suggest that Senegalese youth use a heterogeneous mix of
media platforms (i.e. television, radio, internet) and utilization often occurs
with family members or friends. Additionally, the need for entertainment,
information and connectedness inform media use, mostly concerning sexual and
reproductive health information. Importantly, tensions arise as youth balance
innovative and interactive technologies with traditional and conservative values,
particularly concerning ethical and privacy concerns. Findings support the use of
multipronged intervention approaches that leverage both new media, as well as
traditional media strategies, and that also address lack of health and media
literacy in this population. Implementing health-related interventions across
multiple media platforms provides an opportunity to create an integrated, as
opposed to a disparate, user experience.
PMID- 25113155
TI - Why should working memory be related to incidentally learned sequence structures?
PMID- 25113156
TI - A biomimetic multi-stimuli-response ionic gate using a hydroxypyrene derivation
functionalized asymmetric single nanochannel.
AB - A highly efficient multi-stimuli-response ionic gate that can be activated
separately or cooperatively by pH and UV light has been demonstrated by modifying
the environmental stimuli-responsive molecule 8-hydroxypyrene-1,3,6-trisulfonate
into a track-etched single conical nanochannel. Such a multi-response ionic gate
can find applications in areas such as electronics, actuators, and biosensors.
PMID- 25113154
TI - Intracranial recordings and human memory.
AB - Recent work involving intracranial recording during human memory performance
provides superb spatiotemporal resolution on mnemonic processes. These data
demonstrate that the cortical regions identified in neuroimaging studies of
memory fall into temporally distinct networks and the hippocampal theta activity
reported in animal memory literature also plays a central role in human memory.
Memory is linked to activity at multiple interacting frequencies, ranging from 1
to 500Hz. High-frequency responses and coupling between different frequencies
suggest that frontal cortex activity is critical to human memory processes, as
well as a potential key role for the thalamus in neocortical oscillations. Future
research will inform unresolved questions in the neuroscience of human memory and
guide creation of stimulation protocols to facilitate function in the damaged
brain.
PMID- 25113157
TI - The many generations of sequencing technology.
PMID- 25113160
TI - Sequence-based prediction of protein-binding sites in DNA: comparative study of
two SVM models.
AB - As many structures of protein-DNA complexes have been known in the past years,
several computational methods have been developed to predict DNA-binding sites in
proteins. However, its inverse problem (i.e., predicting protein-binding sites in
DNA) has received much less attention. One of the reasons is that the differences
between the interaction propensities of nucleotides are much smaller than those
between amino acids. Another reason is that DNA exhibits less diverse sequence
patterns than protein. Therefore, predicting protein-binding DNA nucleotides is
much harder than predicting DNA-binding amino acids. We computed the interaction
propensity (IP) of nucleotide triplets with amino acids using an extensive
dataset of protein-DNA complexes, and developed two support vector machine (SVM)
models that predict protein-binding nucleotides from sequence data alone. One SVM
model predicts protein-binding nucleotides using DNA sequence data alone, and the
other SVM model predicts protein-binding nucleotides using both DNA and protein
sequences. In a 10-fold cross-validation with 1519 DNA sequences, the SVM model
that uses DNA sequence data only predicted protein-binding nucleotides with an
accuracy of 67.0%, an F-measure of 67.1%, and a Matthews correlation coefficient
(MCC) of 0.340. With an independent dataset of 181 DNAs that were not used in
training, it achieved an accuracy of 66.2%, an F-measure 66.3% and a MCC of
0.324. Another SVM model that uses both DNA and protein sequences achieved an
accuracy of 69.6%, an F-measure of 69.6%, and a MCC of 0.383 in a 10-fold cross
validation with 1519 DNA sequences and 859 protein sequences. With an independent
dataset of 181 DNAs and 143 proteins, it showed an accuracy of 67.3%, an F
measure of 66.5% and a MCC of 0.329. Both in cross-validation and independent
testing, the second SVM model that used both DNA and protein sequence data showed
better performance than the first model that used DNA sequence data. To the best
of our knowledge, this is the first attempt to predict protein-binding
nucleotides in a given DNA sequence from the sequence data alone.
PMID- 25113158
TI - Safety and efficacy of triple therapy with peginterferon, ribavirin and
boceprevir within an early access programme in Spanish patients with hepatitis C
genotype 1 with severe fibrosis: SVRw12 analysis.
AB - BACKGROUND & AIMS: The addition of protease inhibitors (PIs) changed the
hepatitis C virus (HCV) treatment standards and improved sustained viral response
(SVR) rates in patients with genotype 1 HCV infection. METHODS: Prospective,
multicentre, national registry that includes naive and treatment-experienced
patients with HCV genotype 1 infection, who had bridging fibrosis or cirrhosis
and were treated with triple therapy (peginterferon alfa-2a or alfa-2b, ribavirin
and boceprevir) as compassionate use, and in accordance with the Summary of
Product Characteristics. RESULTS: Most of the patients (68.2%) were male, with a
mean age of 53 years, 75% (n = 128) had HCV 1b genotype and baseline viral load
of 6.2 log. According to prior treatment, 20% of patients were treatment-naive
and 80% had received prior treatment. Approximately 36.5% of patients (n = 62)
reported at least one serious adverse events (SAEs) (total SAEs = 103). The most
common SAEs were neutropenia (57.6%), anaemia (47.6%) and grade 3 thrombopenia
(25.9%). Patients with albumin <3.5 g/dl and bilirubin >2 mg/dl had an increased
relative risk (greater than one-fold) for SAEs, including infections and hepatic
decompensation. In the intent-to-treat analysis (n = 170), the overall percentage
of patients with SVRw12 was 46.5%. In patients with 1 log decrease at week 4
(lead-in phase), the overall SVRw12 rate was 67.0%. In the patients initiating
triple therapy with boceprevir (n = 139), the global response rate was 56.4%. In
a multivariate analysis, an increased probability of achieving SVR was associated
with response to prior treatment (relapsers), >1 log decrease in viral load in
the lead-in phase and baseline albumin >3.5 g/dl. CONCLUSIONS: Triple therapy in
patients with severe fibrosis/cirrhosis is associated with a higher rate of SAE
and a lower rate in comparison with patients with mild disease. However, for
patients with intact liver function, it could be considered as a treatment
option, when other alternatives would not be available.
PMID- 25113162
TI - Compliance, concordance and adherence: what are we talking about?
AB - Adherence or compliance to prescribed treatment regimens is an important and much
debated area of haemophilia care. Many patients are labelled as 'non-adherent'
because they don't do what we say in terms of self- treatment and factor
administration. However, do we engage patients in developing mutually acceptable
treatment programmes which work for them as individuals? If we do, does this
affect self-care and treatment uptake through a supportive relationship which
enhances treatment concordance? Once we have agreed treatment regimens, how do we
measure the success or outcomes of them? This paper discusses these issues, and
some of the tools that are available to assess adherence in a systematic way.
PMID- 25113159
TI - Hydrogen sulphide triggers VEGF-induced intracellular Ca2+ signals in human
endothelial cells but not in their immature progenitors.
AB - Hydrogen sulphide (H2S) is a newly discovered gasotransmitter that regulates
multiple steps in VEGF-induced angiogenesis. An increase in intracellular Ca(2+)
concentration ([Ca(2+)]i) is central to endothelial proliferation and may be
triggered by both VEGF and H2S. Albeit VEGFR-2 might serve as H2S receptor, the
mechanistic relationship between VEGF- and H2S-induced Ca(2+) signals in
endothelial cells is unclear. The present study aimed at assessing whether and
how NaHS, a widely employed H2S donor, stimulates pro-angiogenic Ca(2+) signals
in Ea.hy926 cells, a suitable surrogate for mature endothelial cells, and human
endothelial progenitor cells (EPCs). We found that NaHS induced a dose-dependent
increase in [Ca(2+)]i in Ea.hy926 cells. NaHS-induced Ca(2+) signals in Ea.hy926
cells did not require extracellular Ca(2+) entry, while they were inhibited upon
pharmacological blockade of the phospholipase C/inositol-1,4,5-trisphosphate
(InsP3) signalling pathway. Moreover, the Ca(2+) response to NaHS was prevented
by genistein, but not by SU5416, which selectively inhibits VEGFR-2. However,
VEGF-induced Ca(2+) signals were suppressed by dl-propargylglycine (PAG), which
blocks the H2S-producing enzyme, cystathionine gamma-lyase. Consistent with these
data, VEGF-induced proliferation and migration were inhibited by PAG in Ea.hy926
cells, albeit NaHS alone did not influence these processes. Conversely, NaHS
elevated [Ca(2+)]i only in a modest fraction of circulating EPCs, whereas neither
VEGF-induced Ca(2+) oscillations nor VEGF-dependent proliferation were affected
by PAG. Therefore, H2S-evoked elevation in [Ca(2+)]i is essential to trigger the
pro-angiogenic Ca(2+) response to VEGF in mature endothelial cells, but not in
their immature progenitors.
PMID- 25113163
TI - Dramatic efficacy of brentuximab vedotin in two patients with epidermotropic
cutaneous T-cell lymphomas after treatment failure despite variable CD30
expression.
PMID- 25113165
TI - Does a child's fear of needles decrease through a learning event with needles?
AB - BACKGROUND: Most children have a fear of needles. Suitable preparation can
decrease the pain and fear of needles in hospitals; however, few have examined
how such preparation affects healthy children. This study examined whether
learning with needles decreases fear of needles and changes motivation to get
vaccinations in school-age children and the possible association between fear of
needles and motivation toward vaccinations. METHODS: This study included children
participating in the "Let's Be Doctors" event, which was held in 4 child centers
in Tsukuba city, Ibaraki, Japan. In this event, children learned about injections
and how a vaccine works, and injected a vaccine (water) into skin (sponge) using
a real syringe and imitation needle. Data were collected just before and after
the event by anonymous self-assessment questionnaires that used a 4-point Likert
scale to assess fear of needles, motivation to get vaccinations, recommendation
of vaccinations, and fear toward doctors among the children. Answers were divided
into two categories for statistical analysis. RESULTS: In total, 194 children
participated in the event and 191 children answered the questionnaire (response
rate 98.5%). We analyzed 180 subjects, comprising 79 boys (43.9%) and 94 girls
(52.2%), mean age of 8.1 +/- 1.0 years. The number of children reporting a fear
of needles decreased from 69 (38.3%) before the event to 51 (28.3%) after the
event, and those unwilling to get vaccinations decreased from 48 (26.7%) to 27
(15.0%). Children who reported fear of needles before the event were more
unwilling to get vaccinations than those with no fear of needles (36 [52.2%] vs.
12 [10.8%]), while after the event the number of needle-fearing children
unwilling to get vaccinations decreased to 19 (27.5%). CONCLUSIONS: Children's
fear of needles and unwillingness to get vaccinations were decreased after
experiencing a learning event with needles. The fear of needles is associated
with a negative motivation to get vaccinations in children.
PMID- 25113164
TI - Pharmacological interventions for sleepiness and sleep disturbances caused by
shift work.
AB - BACKGROUND: Shift work results in sleep-wake disturbances, which cause sleepiness
during night shifts and reduce sleep length and quality in daytime sleep after
the night shift. In its serious form it is also called shift work sleep disorder.
Various pharmacological products are used to ameliorate symptoms of sleepiness or
poor sleep length and quality. OBJECTIVES: To evaluate the effects of
pharmacological interventions to reduce sleepiness or to improve alertness at
work and decrease sleep disturbances whilst off work, or both, in workers
undertaking shift work in their present job and to assess their cost
effectiveness. SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE, PubMed and
PsycINFO up to 20 September 2013 and ClinicalTrials.gov up to July 2013. We also
screened reference lists of included trials and relevant reviews. SELECTION
CRITERIA: We included all eligible randomised controlled trials (RCTs), including
cross-over RCTs, of pharmacological products among workers who were engaged in
shift work (including night shifts) in their present jobs and who may or may not
have had sleep problems. Primary outcomes were sleep length and sleep quality
while off work, alertness and sleepiness, or fatigue at work. DATA COLLECTION AND
ANALYSIS: Two authors independently selected studies, extracted data and assessed
risk of bias in included trials. We performed meta-analyses where appropriate.
MAIN RESULTS: We included 15 randomised placebo-controlled trials with 718
participants. Nine trials evaluated the effect of melatonin and two the effect of
hypnotics for improving sleep problems. One trial assessed the effect of
modafinil, two of armodafinil and one examined caffeine plus naps to decrease
sleepiness or to increase alertness.Melatonin (1 to 10 mg) after the night shift
may increase sleep length during daytime sleep (mean difference (MD) 24 minutes,
95% confidence interval (CI) 9.8 to 38.9; seven trials, 263 participants, low
quality evidence) and night-time sleep (MD 17 minutes, 95% CI 3.71 to 30.22;
three trials, 234 participants, low quality evidence) compared to placebo. We did
not find a dose-response effect. Melatonin may lead to similar sleep latency
times as placebo (MD 0.37minutes, 95% CI - 1.55 to 2.29; five trials, 74
participants, low quality evidence).Hypnotic medication, zopiclone, did not
result in significantly longer daytime sleep length compared to placebo in one
low quality trial and we could not use the data from the study on
lormetazepam.Armodafinil taken before the night shift probably reduces sleepiness
by one point on the Karolinska Sleepiness Scale (KSS) (MD -0.99, 95% CI -1.32 to
0.67; range 1 to 10; two trials, 572 participants, moderate quality evidence) and
increases alertness by 50 ms in a simple reaction time test (MD -50.0, 95% CI
85.5 to -15.5) at three months' follow-up in shift work sleep disorder patients.
Modafinil probably has similar effects on sleepiness (KSS) (MD -0.90, 95% CI
1.45 to -0.35; one trial, 183 participants, moderate quality evidence) and
alertness in the psychomotor vigilance test in the same patient group. Post
marketing, severe skin reactions have been reported. Adverse effects reported by
trial participants were headache, nausea and a rise in blood pressure. There were
no trials in non-patient shift workers.Based on one trial, caffeine plus pre
shift naps taken before the night shift decreased sleepiness (KSS) (MD -0.63, 95%
CI -1.09 to -0.17).We judged most trials to have a low risk of bias even though
the randomisation method and allocation concealment were often not described.
AUTHORS' CONCLUSIONS: There is low quality evidence that melatonin improves sleep
length after a night shift but not other sleep quality parameters. Both modafinil
and armodafinil increase alertness and reduce sleepiness to some extent in
employees who suffer from shift work sleep disorder but they are associated with
adverse events. Caffeine plus naps reduces sleepiness during the night shift, but
the quality of evidence is low. Based on one low quality trial, hypnotics did not
improve sleep length and quality after a night shift.We need more and better
quality trials on the beneficial and adverse effects and costs of all
pharmacological agents that induce sleep or promote alertness in shift workers
both with and without a diagnosis of shift work sleep disorder. We also need
systematic reviews of their adverse effects.
PMID- 25113166
TI - The effects of steroid hormone exposure on direct gene regulation.
AB - Steroid hormones have been widely overlooked as controllers of gene expression.
Through the mechanisms of gene expression (DNA methylation, histone methylation,
and RNAi), we discuss the impact of normal reproductive templates on the
pulsatility and amplitude of potential gene-regulating treatment protocols. By
examining the interactions of estradiol (E2) and progesterone (P4) in women, we
propose that changes in physiologic reproductive hormone templates of exposure
and timing can affect fertility and even cancer through the silencing or
amplification of gene products; such as P53 and Bcl-2 in women. We suggest that
uncontrolled hormone levels, due to aging and/or the environment, may be restored
to a normal youthful template of gene expression through the fluctuating
exogenous application of E2 and P4 that mimic the normal hormonal milieu of
reproductive health. Furthermore, we hypothesize that restoration of normal
hormone levels may lead to a lower risk of the chronic illnesses of aging and a
better quality of life in patients suffering those conditions.
PMID- 25113167
TI - Activity-dependent alterations in the sensitivity to BDNF-TrkB signaling may
promote excessive dendritic arborization and spinogenesis in fragile X syndrome
in order to compensate for compromised postsynaptic activity.
AB - Fragile X syndrome (FXS), the most common cause of inherited human mental
retardation, results from the loss of function of fragile X mental retardation
protein (FMRP). To date, most researchers have thought that FXS neural
pathologies are primarily caused by extreme dendritic branching and spine
formation. With this rationale, several researchers attempted to prune dendritic
branches and reduce the number of spines in FXS animal models. We propose that
increased dendritic arborization and spinogenesis in FXS are developed rather as
secondary compensatory responses to counteract the compromised postsynaptic
activity during uncontrollable metabotropic glutamate receptor (mGluR)-dependent
long-term depression (LTD). When postsynaptic and electrical activities become
dampened in FXS, dendritic trees can increase their sensitivity to brain-derived
neurotrophic factor (BDNF) by using the molecular sensor called eukaryotic
elongation factor 2 (eEF2) and taking advantage of the tight coupling of mGluR
and BDNF-TrkB signaling pathways. Then, this activity-dependent elevation of the
BDNF signaling can strategically alter dendritic morphologies to foster branching
and develop spine structures in order to improve the postsynaptic response in
FXS. Our model suggests a new therapeutic rationale for FXS: correcting the
postsynaptic and electrical activity first, and then repairing structural
abnormalities of dendrites. Then, it may be possible to successfully fix the
dendritic morphologies without affecting the survival of neurons. Our theory may
also be generalized to explain aberrant dendritic structures observed in other
neurobehavioral diseases, such as tuberous sclerosis, Rett syndrome,
schizophrenia, and channelopathies, which accompany high postsynaptic and
electrical activity.
PMID- 25113168
TI - Editorial.
PMID- 25113169
TI - Evaluation of radiocaesium wash-off by soil erosion from various land uses using
USLE plots.
AB - Radiocaesium wash-off associated with soil erosion in different land use was
monitored using USLE plots in Kawamata, Fukushima Prefecture, Japan after the
Fukushima Dai-ichi Nuclear Power Plant accident. Parameters and factors relating
to soil erosion and (137)Cs concentration in the eroded soil were evaluated based
on the field monitoring and presented. The erosion of fine soil, which is defined
as the fraction of soil overflowed along with discharged water from a sediment
trap tank, constituted a large proportion of the discharged radiocaesium. This
indicated that the quantitative monitoring of fine soil erosion is greatly
important for the accurate evaluation of radiocaesium wash-off. An exponential
relationship was found between vegetation cover and the amount of eroded soil.
Moreover, the radiocaesium concentrations in the discharged soil were greatly
affected by the land use. These results indicate that radiocaesium wash-off
related to vegetation cover and land use is crucially important in modelling
radiocaesium migration.
PMID- 25113170
TI - Selection of controls in the study of human neurodegenerative diseases in old
age.
AB - Human post-mortem brain tissue, mostly provided by brain banks, is precious
because most human neurodegenerative diseases are restricted in their complete
forms to human beings. However, the agonal state, post-mortem delay between death
and tissue processing, variable vulnerability of chromatin, RNAs, proteins and
metabolites can compromise the usability of the tissue material. Such factors
must be considered and assessed in every experimental approach. The use of
controls for comparative purposes to analyze diseased cases is crucial as the
basic conditions of controls must be the same as those encountered in problem
cases. Age, gender, region, hemisphere, and clear characterisation of objective
neuropathological changes (e.g., Alzheimer's disease stages of Braak and Braak)
in matching controls and problem cases must be considered in every study, and
data must be clearly specified when presenting materials and methods in
publications. Additional care must be taken regarding atypical neurodegenerative
alterations, concomitant pathologies, and systemic diseases, together with drug
consumption and treatments. The absence of neurological and mental symptoms and
signs, although a sine qua non condition, is not sufficient to match control and
problem cases for research.
PMID- 25113172
TI - Vacancy patterning and patterning vacancies: controlled self-assembly of
fullerenes on metal surfaces.
AB - A density functional theory study accounting for van der Waals interactions
reveals the potential of metal surface vacancies as anchor points for the
construction of user-defined 2D patterns of adsorbate molecules via a controlled
self-assembly process. Vice versa, energetic criteria indicate the formation of
regular adsorbate-induced vacancies after adsorbate self-assembly on clean
surfaces. These processes are exemplified by adsorbing C60 fullerene on Al(111),
Au(111), and Be(0001) surfaces with and without single, triple, and septuple atom
pits. An analysis of vacancy-adatom formation energetics precedes the study of
the adsorption processes.
PMID- 25113173
TI - Bis[N,N'-diisopropylbenzamidinato(-)]silicon(II): Lewis acid/base reactions with
triorganylboranes.
AB - Reaction of the donor-stabilized silylene 1 (which is three-coordinate in the
solid state and four-coordinate in solution) with BEt3 and BPh3 leads to the
formation of the Lewis acid/base complexes 2 and 3, respectively, which are the
first five-coordinate silicon compounds with an Si?B bond. These compounds were
structurally characterized by crystal structure analyses and by multinuclear NMR
spectroscopic studies in the solid state and in solution. Additionally, the
bonding situation in 2 and 3 was analyzed by quantum chemical studies.
PMID- 25113171
TI - Insulin sensitizers improve learning and attenuate tau hyperphosphorylation and
neuroinflammation in 3xTg-AD mice.
AB - Sporadic Alzheimer's disease (AD) is a multifactorial metabolic brain disorder
characterized by progressive neurodegeneration. Decreased brain energy and
glucose metabolism occurs before the appearance of AD symptoms and worsens while
the disease progresses. Deregulated brain insulin signaling has also been found
in AD recently. To restore brain insulin sensitivity and glucose metabolism,
pioglitazone and rosiglitazone, two insulin sensitizers commonly used for
treating type 2 diabetes, have been studied and shown to have some beneficial
effects in AD mouse models. However, the molecular mechanisms of the beneficial
effects remain elusive. In the present study, we treated the 3xTg-AD mice, a
widely used mouse model of AD, with pioglitazone and rosiglitazone for 4 months
and studied the effects of the treatments on cognitive performance and AD-related
brain alterations. We found that the chronic treatment improved spatial learning,
enhanced AKT signaling, and attenuated tau hyperphosphorylation and
neuroinflammation. These findings shed new light on the possible mechanisms by
which these two insulin sensitizers might be useful for treating AD and support
further clinical trials evaluating the efficacy of these drugs.
PMID- 25113174
TI - Incidence of alcohol use disorders among Hispanic subgroups in the USA.
AB - OBJECTIVE: Hispanics are the largest ethnic minority group in the USA and a
fairly heterogeneous group. But this heterogeneity has usually been ignored by
grouping them into a single category. The objective of this study is to challenge
that practice by providing alcohol use disorders (AUD) incidence and risk
estimates across Hispanic subgroups. METHODS: A subsample of Hispanics (n = 2371)
and non-Hispanic whites (n = 7741) at risk for AUD who participated in the first
and second wave of the National Epidemiological Survey on Alcohol and Related
Conditions was analyzed. Weighted incidence for AUD was calculated across
Hispanic subgroups. A weighted modified Poisson generalized linear model was used
to estimate relative risks. RESULTS: Compared with non-Hispanic whites, Puerto
Ricans have the highest AUD incidence (3.6%; 95% CI: 0.5, 6.7) followed by
Mexican-Americans (2.5%; 95% CI: 1.5, 3.6), Other Hispanics (1.6%; 95% CI: 0.1,
3.1) and Cuban-Americans (0.6%; 95% CI: 0.1, 1.2). In contrast, weighted adjusted
relative risk estimates for Mexican-Americans were (RR = 3.2; 95% CI: 1.7, 6.2)
but for Puerto Ricans (RR = 2.2; 95% CI: 1.0, 5.0) it was somewhat attenuated but
still significant (P = 0.049). No difference was found for Cuban-Americans or
Other Hispanics. CONCLUSIONS: The annual incidence and risk for AUD varies
greatly among Hispanic subgroups. Nonetheless, the practice of categorizing
Hispanics as a homogenous ethnic group still continues. Our findings suggest that
this practice is not only inappropriate, but also hinders a better understanding
of AUD etiology, prevention, treatment and rehabilitation in the largest ethnic
minority group in the USA.
PMID- 25113175
TI - Assessing restrictiveness of national alcohol marketing policies.
AB - AIMS: To develop an approach for monitoring national alcohol marketing policies
globally, an area of the World Health Organization's (WHO) Global Alcohol
Strategy. METHODS: Data on restrictiveness of alcohol marketing policies came
from the 2002 and 2008 WHO Global Surveys on Alcohol and Health. We included four
scales in a sensitivity analysis to determine optimal weights to score countries
on their marketing policies and applied the selected scale to assess national
marketing policy restrictiveness. RESULTS: Nearly, 36% of countries had no
marketing restrictions. The overall restrictiveness levels were not significantly
different between 2002 and 2008. The number of countries with strict marketing
regulations did not differ across years. CONCLUSION: This method of monitoring
alcohol marketing restrictiveness helps track progress towards implementing WHO'S
Global Alcohol Strategy. Findings indicate a consistent lack of restrictive
policies over time, making this a priority area for national and global action.
PMID- 25113177
TI - Blood levels of polychlorinated biphenyls and their hydroxylated metabolites in
Baikal seals (Pusa sibirica): emphasis on interspecies comparison, gender
difference and association with blood thyroid hormone levels.
AB - We have previously demonstrated that Baikal seals (Pusa sibirica) are still being
exposed to polychlorinated biphenyls (PCBs), and the population is at risk. In
the present study, we measured the residue levels of PCBs and their hydroxylated
metabolites (OH-PCBs) in the blood of Baikal seals and assessed the impact of OH
PCBs on the thyroid function. Blood concentrations of PCBs and OH-PCBs were in
the range of 2.8-130 ng g(-1)wet wt. and 0.71-4.6 ng g(-1)wetwt., respectively.
Concentrations of higher-chlorinated OH-PCBs (hexa- to octa-PCBs) were more than
70% to total OH-PCB concentrations, indicating Baikal seals are mostly risked by
higher-chlorinated OH-PCBs. High levels of 4OH-CB146 and 4OH-CB187 and low levels
of 4OH-CB107/4'OH-CB108 found in Baikal seals were different from those in other
phocidae species, suggesting the unique drug-metabolizing enzyme activities
and/or contamination sources in this species. Concentrations of some OH-PCBs in
males were significantly higher than those in females. These results suggest that
these isomers may be preferentially transferred from mother to pup via cord
blood. However, concentrations of almost all the isomers were not significantly
correlated with the levels of blood total T3 and T4, implying less impact of PCB
related compounds on the thyroid hormone circulation.
PMID- 25113176
TI - The relationships between alcohol source, autonomy in brand selection, and brand
preference among youth in the USA.
AB - AIMS: We aimed to describe the sources from which youth in the USA commonly
obtain alcohol, their role in selecting the brands they drink and the
relationship of these variables to their indicated alcohol brand preferences.
METHODS: We recruited 1031 underage drinkers in the age range of 13-20 through an
internet panel managed by Knowledge Networks. Respondents completed an online
survey assessing their recent brand-specific alcohol use, the source of their
most recently consumed alcohol and whether the respondent or another person
selected the brand they drank. RESULTS: Alcohol sources were more often passive
than transactional. Nearly equal proportions of youth reported that they did
versus did not choose the brand of their most recent drink. Analysis revealed
that the brand preferences of passive versus active source drinkers were highly
similar, as were the brand preferences of respondent versus non-respondent choice
drinkers. Stratification of respondents by age did not significantly change these
results. CONCLUSION: Our findings suggest that youth are consuming a homogenous
list of preferred brands regardless of the source of their most recently obtained
alcohol or who selected the brand they drank.
PMID- 25113178
TI - Partition of organochlorine concentrations among suspended solids, sediments and
brown mussel Perna perna, in tropical bays.
AB - For evaluating the brown mussel Perna perna as a sentinel organism regarding
environmental concentrations of organochlorine pesticides (OCPs) and
polychlorinated biphenyls (PCBs), the present study reports original data on the
relationship between the concentrations of these chemicals in bottom surface
sediments, suspended solids (SS) and concentrations bioaccumulated by this
bivalve. Three P. perna cultivation areas, located at three bays in southeastern
Brazil were used in this study. The three estuaries are under different degrees
of environmental impact. Variations in the OCP and PCB concentrations
bioaccumulated by the bivalves tended to be similar to those observed in the
sediment, but differed from those found in SS. This latter difference might
suggest that the SS trapping apparatuses should have been left in place for
approximately 60 days (not only 15 days). This longer period would allow the
integration of the environmental variability of the OCP and PCB burden adsorbed
to this compartment. Authors encourage future studies to evaluate P. perna
exposure to OCPs and PCBs through the evaluation of sediment concentrations.
PMID- 25113179
TI - Contamination profiles of perfluoroalkyl substances in five typical rivers of the
Pearl River Delta region, South China.
AB - A survey on contamination profiles of eighteen perfluoroalkyl substances (PFASs)
was performed via high performance liquid chromatography-tandem mass spectrometry
for surface water and sediments from five typical rivers of the Pearl River Delta
region, South China in summer and winter in 2012. The total concentrations of the
PFASs in the water phase of the five rivers ranged from 0.14 to 346.72 ng L(-1).
The PFAS concentrations in the water phase were correlated positively to some
selected water quality parameters such as chemical oxygen demand (COD) (0.7913)
and conductivity (0.5642). The monitoring results for the water samples showed
significant seasonal variations, while those for the sediment samples showed no
obvious seasonal variations. Among the selected 18 PFASs, perfluorooctane
sulfonic acid (PFOS) was the dominant PFAS compound both in water and sediment
for two seasons with its maximum concentration of 320.5 ng L(-1) in water and
11.4 ng g(-1) dry weight (dw) in sediment, followed by perfluorooctanoic acid
(PFOA) with its maximum concentration of 26.48 ng L(-1) in water and 0.99 ng g(
1) dw in sediment. PFOS and PFOA were found at relatively higher concentrations
in the Shima River and Danshui River than in the other three rivers (Xizhijiang
River, Dongjiang River and Shahe River). The principal component analysis for the
PFASs concentrations in water and sediment separated the sampling sites into two
groups: rural and agricultural area, and urban and industrial area, suggesting
the PFASs in the riverine environment were mainly originated from industrial and
urban activities in the region.
PMID- 25113180
TI - Distribution of organochlorine pesticides in sediments from Yangtze River Estuary
and the adjacent East China Sea: implication of transport, sources and trends.
AB - Thirty-eight surface sediments and two sediment cores were collected from Yangtze
River Estuary (YRE) and adjacent East China Sea (ECS) to study the distribution
patterns, origins, potential transport and burden of organochlorine pesticides
(OCPs) in the marginal sea. Residues of OCPs ranged from 0.190 to 5.17 ng g(-1)
dry weight with a distinct "band type" pattern under the control of Yangtze River
inputs and ECS circulation system. Differences in transmission media and redox
conditions in situ respectively resulted in the divergent distributions of
alpha/beta-HCH and DDD/DDE. The compositional pattern analysis implied that OCPs
in the inner shelf of ECS were derived from both "weathered" and fresh sources,
whereas those in the outer shelf of ECS had undergone high metabolism. Concurrent
with the land-sea migration, vertical profiles of sediment cores showed
increasing trends or rebound since the 1990s, characteristic of two evident
"jumps" of DDE+DDD/DDT and DDT/DDE ratios. Moreover, the primary distribution
pattern founded for HCHs and the considerable mass inventories calculated (6.20
metric tones for OCPs) together suggested that the contaminated sediments in the
studied area to be a potential source of OCPs to the global ocean.
PMID- 25113181
TI - PAHs in decaying Quercus ilex leaf litter: mutual effects on litter decomposition
and PAH dynamics.
AB - The investigation of the relationships between litter decomposition and
polycyclic aromatic hydrocarbons (PAHs) is important to shed light not only on
the effects of these pollutants on fundamental ecosystem processes, such as
litter decomposition, but also on the degradation of these pollutants by soil
microbial community. This allows to understand the effect of atmospheric PAH
contamination on soil PAH content via litterfall. At this aim, we studied mass
and PAH dynamics of Quercus ilex leaf litters collected from urban, industrial
and remote sites, incubated in mesocosms under controlled conditions for 361d.
The results highlighted a litter decomposition rate of leaves sampled in
urban>industrial>remote sites; the faster decomposition of litter of the urban
site is also related to the low C/N ratio of the leaves. The PAHs showed
concentrations at the beginning of the incubation of 887, 650 and 143 ng g(
1)d.w., respectively in leaf litters from urban, industrial and remote sites. The
PAHs in litter decreased along the time, with the same trend observed for mass
litter, showing the highest decrease at 361 d for the urban leaf litter. Anyway,
PAH dynamics in all the litters exhibited two phases of loss, separated by a PAH
increase observed at 246 d and mainly linked to benzo[e]pyrene.
PMID- 25113182
TI - Residues and chiral signatures of organochlorine pesticides in mollusks from the
coastal regions of the Yangtze River Delta: source and health risk implication.
AB - The residues and enantiomeric fractions of organochlorine pesticides (OCPs) were
measured in 11 mollusk species collected from the coastal areas along the Yangtze
River Delta to evaluate the status, potential sources, and health risks of
pollution in these areas. The concentrations of DDTs, HCHs, and chlordanes ranged
from 6.22 to 398.19, 0.66-7.11, and 0.14-4.08 ng g(-1) based on wet weight,
respectively; DDTs and HCHs have the highest values, globally. The DDTs increased
and the HCHs decreased compared to historical data. Both the box-and-whisker
plots and the one-way ANOVA tests indicated that the OCP levels varied little
between sampling locations and organism species. The compositions of the DDTs and
HCHs suggested a cocktail input pattern of fresh and weathered technical
products. The comparative EF values for the alpha-HCH between the sediments and
mollusks, as well as the lack of any discernible difference in the relative
proportions of HCH isomers among different species from the same sampling site
implied that the HCH residues in the mollusks came directly from the surrounding
environment. However, the biotransformation of DDTs in mollusks cannot be
precluded. The assessments performed based on several available guidelines
suggested that although no significant human health risks were associated with
the dietary intake of OCPs, the concentrations of DDTs exceeded the maximum
residual limits of China and many developed nations. Moreover, an increased
lifetime cancer risk from dietary exposure to either DDTs or HCHs remains a
possibility. Because non-racemic OCP residues are common in the mollusk samples,
our results suggest a need to further explore the levels and toxicity of the
chiral contaminants in mollusks and other foodstuff to develop the human risk
assessment framework based on chiral signatures.
PMID- 25113183
TI - Comparison of the sorption behaviors and mechanisms of perfluorosulfonates and
perfluorocarboxylic acids on three kinds of clay minerals.
AB - The sorption of four perfluoroalkyl acids (PFAAs) [perfluorooctane sulfonate
(PFOS), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA) and
perfluorohexanoic acid (PFHxA)] on three typical minerals [montmorillonite (MM),
kaolinite (KL) and hematite (HM)] was studied. The sorption of PFOS and PFHxS was
much stronger than PFOA and PFHxA. The sorption of each PFAA on the minerals
followed an order of HM>KL>MM, even though MM was positively while KL and HM were
negatively charged, implying that the sorption is driven by some other
interactions besides electrostatic attraction. The sorption decreased with an
increase in pH and a decrease in ionic strength of the solution, and their
impacts on PFOS were much stronger than other three PFAAs. Surface complexing and
hydrogen-bonding could make great contributions to the sorption of PFOS on the
minerals. The results are important for understanding the transport and fate of
PFAAs in sediment and ground water.
PMID- 25113184
TI - Study of penetration behavior of PCB-DNAPL in a sand layer by a column
experiment.
AB - To better understand the infiltration performances of high concentration PCB oils
(KC-300 and KC-1000 polychlorinated biphenyl (PCB) mixtures), representative
dense non-aqueous phase liquid (DNAPL), under both saturated and unsaturated
conditions, we conducted experiments on a sand column filled with Toyoura
Standard Sand. When PCB oil with the volume comparable to the total porosity in
the column was supplied, the residual PCB concentrations under PCB-water
conditions were 4.9*10(4)mgkg(-1) in KC-300 and 3.9*10(4)mgkg(-1) in KC-1000.
Under PCB-air conditions, residual PCB concentrations were 6.0*10(4)mgkg(-1) and
2.4*10(5)mgkg(-1) in the upper and lower parts for KC-300 and 3.6*10(4)mgkg(-1)
and 1.5*10(5)mgkg(-1) in those for KC-1000, respectively, while the rest of the
PCBs were infiltrated. On the other hand, when a small amount of PCB oil with the
volume far smaller than the total porosity in the column was supplied, the
original PCBs were not transported via water permeation. However, lower
chlorinated PCB congeners-e.g., di- or tri-chlorinated biphenyls-preferentially
dissolved and were infiltrated from the bottom of the column. These propensities
on PCB oil infiltration can be explained in conjunction with the degree of PCB
saturation in the sand column.
PMID- 25113185
TI - Distribution of persistent organic pollutants (POPs) in cultured mussels from the
Croatian coast of the Adriatic Sea.
AB - In this study we investigated the distribution of 7 organochlorine pesticides
(OCPs) and 17 polychlorinated biphenyl (PCBs) congeners in the edible tissue of
the blue mussels (Mytilusgalloprovincialis) collected at 15 shellfish breeding
farms and 1 harvesting area along the Croatian Adriatic coast. All analyzed OCPs
were found in all samples (0.011-1.47 ng g(-)(1) w.wt.). Concentrations of PCB
congeners in positive samples ranged between 0.007 and 7.66 ng g(-)(1) w.wt. The
most abundant compounds were gamma-HCH, PCB-138 and PCB-153. Overall levels of
PCBs and OCPs were in the lower end of the concentration ranges reported in
literature. Significant differences of all contaminants were recorded between
seasons, with higher values in the warmer part of the year. Results of the
evaluation of the risks to human health associated with consumption of the
mussels containing organic contaminants suggest that the levels of these
compounds in mussels do not pose any threat for consumers of cultivated mussels.
PMID- 25113186
TI - Study on the impact of industrial flue gases on the PCDD/Fs congener profile in
ambient air.
AB - The aim of this study was to examine the impact of emissions from combustion
processes from sinter, medical, waste and sewage waste incineration plants on the
PCDD and PCDF congener profile in ambient air in Krakow (city in Poland). The
subject matter of the study were air samples from the outskirts and the city
center. It was found that in flue gases from industrial sources and in ambient
air the share of PCDF congeners in relation to the total content of PCDD/Fs was
higher than the share of PCDDs. However, in air samples collected in the city
center, this relationship was reversed. The PCDD congener profiles in flue gases
and in air samples are comparable. However, in the samples from the city centre,
the share of OCDD is significantly higher and amounts to about 80%. The PCDF
congener shares show higher spatial diversity, although in all the analyzed air
samples, ODCF and 1,2,3,4,6,7,8 HpCDF dominated. Analyzing the share of congeners
in regard to the sum of PCDDs/Fs a mutual resemblance of air from the suburbs,
exhaust gases from the sinter ore and sewage sludge incinerator plant was
observed. The study showed a similarity between the profile of congeners in air
from the city centre and exhaust gases from the medical waste incinerator.
PMID- 25113187
TI - Polychlorinated biphenyls removal from contaminated soils using a transportable
indirect thermal dryer unit: implications for emissions.
AB - An assessment in China of the application of a transportable indirect thermal
dryer unit for the remediation of soils contaminated with polychlorinated
biphenyls (PCBs) demonstrated that it is well suited to remove PCBs from soils. A
remarkable reduction of total PCBs in soils from 163-770 MUg g(-1) to 0.08-0.15
MUg g(-1) was achieved. This represented removal efficiencies of greater than
99.9% and an approximate 100% removal of the toxic equivalent of the PCBs.
Furthermore, the emissions to the atmosphere from the unit were in compliance
with current PCBs regulations. In conclusion, remediation of PCBs-contaminated
soils based on a transportable indirect thermal dryer unit appears to be a highly
efficient and environmentally sound treatment technology that has huge
implications for cleaning thousands of regionally dispersed sites of PCBs
contamination in China.
PMID- 25113188
TI - Characterization and fate of polychlorinated biphenyls, polychlorinated dibenzo-p
dioxins and polychlorinated dibenzofurans in soils and sediments at the
Portsmouth Gaseous Diffusion Plant, Ohio.
AB - The U.S. Department of Energy Portsmouth Gaseous Diffusion Plant is in the early
stages of decommissioning and decontamination. During operations, the site drew a
large amount of electric power and had multiple large switchyards on site. These
are a source of polychlorinated biphenyls (PCB) contamination to both on-site and
off-site streams. Some soil remediation has been completed in the main
switchyard. During 2011 and 2012, fifteen sites were sampled at the surface (<10
cm) and subsurface (20-30 cm) to characterize the extent of PCB contamination, to
identify weathering and migration of PCB contamination and to explore potential
polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF)
contamination due to transformer fires and explosions in the 1950s and 1960s.
Stagnant sites tended to exhibit more migration of contamination to deeper
sediments than sites with fast-moving waters, and the highest concentrations were
found at the bottom of a settling pond. A signature set of five dioxin-like PCBs
were consistently found across the site with higher concentrations in carbon rich
surface sediments. PCB concentrations had a significant inverse correlation with
clay content, suggesting that PCBs did not bind to clays at this site.
Remediation has reduced PCB concentrations throughout the site compared to levels
found in previous studies and long-term upkeep of sediment lagoons is necessary
to retain PCB and dioxin-rich sediments. The flow regimen, organic carbon and
clay content play a very important role in the fate of PCBs in the environment at
the surface as well as downward migration.
PMID- 25113189
TI - QSAR studies of bioconcentration factors of polychlorinated biphenyls (PCBs)
using DFT, PCS and CoMFA.
AB - The bioconcentration factors (BCFs) of 58 polychlorinated biphenyls (PCBs) were
modeled by quantitative structure-activity relationship (QSAR) using density
functional theory (DFT), the position of Cl substitution (PCS) and comparative
molecular field analysis (CoMFA) methods. All the models were robust and
predictive, and especially, the best CoMFA model was significant with a
correlation coefficient (R(2)) of 0.926, a cross-validation correlation
coefficient (Q(2)) of 0.821 and a root mean square error estimated (RMSE) of
0.235. The results indicate that the electrostatic descriptors play a more
significant role in BCFs of PCBs. Additionally, a test set was used to compare
the predictive ability of our models to others, and results show that our CoMFA
model present the lowest RMSE. Thus, the models obtain in this work can be used
to predict the BCFs of remaining 152 PCBs without available experimental values.
PMID- 25113190
TI - Bioaccumulation and biomagnification of persistent organic pollutants in Indo
Pacific humpback dolphins (Sousa chinensis) from the Pearl River Estuary, China.
AB - Indo-Pacific humpback dolphins (Sousa chinensis) are apex predators in the Pearl
River Estuary waters (PRE) of China. PCBs, DDTs and other organochlorine
pesticides (OCPs) (e.g., HCHs, HCB, mirex and dieldrin) were analysed in blubber
samples of 45 dolphins and 10 prey fishes of S. chinensis collected from 2004 to
2013 in the PRE region to investigate the bioaccumulation and potential
biomagnification of persistent organic pollutants (POPs). DDTs were the most
abundant residue in the dolphins, with an average of 6,2700 ng g(-1) wet weight
(ww), followed by PCBs (average: 1,790 ng g(-1) ww) and other OCPs including
?HCHs, mirex, endrin, ?chlordanes, HCB, dieldrin, aldrin, heptachlor, and
pentachlorobenzene. The concentrations of PCBs and DDTs in male dolphins
significantly increased with age and length. In contrast, female dolphins did not
show obvious bioaccumulation trends with age and body length, possibly due to the
lactational and parturitional transfer of these compounds. Compared with the POP
residues in the prey fishes, the concentrations of PCBs, DDTs, and HCHs in the
dolphin blubber increased by factors of 99, 212, and 5, respectively, whereas the
residue levels of the other OCPs increased 2-185 times, indicating a potentially
significant biomagnification in the top predators. The potential biomagnification
factors calculated for most POPs were significantly higher than those in the
cetacean species from other regions.
PMID- 25113191
TI - Chronic effects of PFOA and PFOS on sexual reproduction of freshwater rotifer
Brachionus calyciflorus.
AB - Rotifers play an important role in the dynamics of freshwater and coastal marine
ecosystems, and are also important tools for assessing toxicity in aquatic
environments. In this study, the effects of perfluorooctane sulfonate (PFOS) and
perfluorooctanoic acid (PFOA) on the population growth rate and resting egg
production of rotifer Brachionus calyciflorus were investigated. Reproductive
bioassays indicated that PFOS increased the rotifer population growth rate at the
concentration ?2.0 mg L(-1), and inhibited it at higher concentrations. For PFOA,
the inhibition of population growth rate was observed when the concentration was
greater than 4.0 mg L(-1). Exposure to PFOS (0.25 mg L(-1)) or PFOA (2.0 mg L(
1)) increased the mictic ratios of unexposed rotifer offspring. Population
variation and increased mictic ratios were likely the two major factors leading
to decline of resting egg production. The resting eggs formed under exposure to
PFOA/PFOS in the range of 0.125-2.0 mg L(-1) showed higher hatching percentages
in the control medium than that without PFOA/PFOS exposure. When the resting eggs
were formed in the control medium and incubated in media with different levels of
PFOA/PFOS, higher hatching percentages were induced by PFOS but lower hatching
percentages induced by PFOA. The effects on the hatching rate of resting eggs
with PFOA/PFOS exposure during the hatching period were greater than those with
exposure during resting egg formation period, and the effect of PFOS was greater
than that of PFOA. Both PFOA and PFOS exhibited slight effect on the hatching
pattern.
PMID- 25113193
TI - Mechanisms of transformation of polychlorinated diphenyl ethers into
polychlorinated dibenzo-p-dioxins and dibenzofurans.
AB - This study presents a detailed mechanistic account of the formation of
polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs)
from polychlorinated diphenyl ethers (PCDEs). It applies the recently developed
meta hybrid M06-2X functional and deploys the 2,2'-dichlorodiphenylether (2,2'
DCDE) molecule as a representative model compound for all PCDEs congeners. We
find that, exceedingly high activation enthalpies prevent the direct formation of
PCDFs from PCDEs via unimolecular elimination of HCl or Cl2. Rather, loss of an
ortho H/Cl atom initiates the transformation of PCDEs into PCDD/Fs. Subsequent
formation of PCDFs takes place through ring-closure reactions with modest
activation enthalpies, whereas the addition of a ground state oxygen molecule at
an apparent ortho radical site of a PCDE congener commences a complex, yet very
exothermic, mechanism leading to the formation of PCDDs. Splitting the ether
linkage through H/Cl addition at the pivot carbon constitutes a major source for
the formation of chlorophenoxy radicals and chlorobenzene molecules. Our kinetic
and mechanistic analyses demonstrate that, the degree and pattern of chlorination
of PCDEs display a negligible effect on the formation pathways of PCDD/Fs from
PCDEs.
PMID- 25113192
TI - Consumption of foods of animal origin as determinant of contamination by
organochlorine pesticides and polychlorobiphenyls: results from a population
based study in Spain.
AB - The level of contamination with persistent organic pollutants (POPs) and dietary
habits and food consumption was extensively studied in the population from the
Canary Islands (Spain). Because foodstuffs of animal origin are well known to be
prominent contributors to these contaminants, the current study aimed to assess
the role of the dietary intake of animal products as a probability factor for
increased serum POPs. The intake of animal products (dietary variables) as a
determining factor for serum POP levels was investigated using multivariate
statistical models. Our results showed that while poultry, rabbit, and cheese
consumption increases the probability of having high levels of non-DDT-derivative
pesticides, sausage, yogurt, lard, and bacon consumption decreases the
probability of having high levels of these pesticides. In addition, poultry,
rabbit, eggs, cream, and butter consumption increased the probability of having
detectable levels of marker PCB, while dairy desserts decreased the probability
of having detectable levels of these PCBs. On the contrary, sausage and meat
consumption increased the probability of having detectable levels of dioxin-like
PCBs (DL-PCBs). The current results confirm that dietary intake of foodstuffs of
animal origin is a relevant risk factor for the accumulation of POPs (and
therefore their serum levels). Our study indicates that the analysis of dietary
patterns may be useful for identifying those individuals that will probably
present a high body burden of POPs. Because POPs can exert deleterious effects on
human health, the identification of populations at risk of being highly
contaminated is mandatory in order to implement policies that minimize the
exposure to these compounds.
PMID- 25113195
TI - Long-term potential of in situ chemical reduction for treatment of
polychlorinated biphenyls in soils.
AB - Polychlorinated biphenyls (PCBs) are well-known for being hydrophobic and
persistent in the environment. Although many treatment approaches have been
demonstrated to result in degradation of PCBs in water or water/cosolvent
systems, few examples exist where such approaches have been applied successfully
for PCB degradation in soil-water systems. A possible explanation for the limited
treatment of PCBs in soil-water systems is that reactants that are capable of
degrading PCBs in the aqueous phase are unlikely to persist long enough to
achieve meaningful treatment of slowly-desorbing PCBs associated with the soil
phase. To investigate this explanation, laboratory studies were conducted to
evaluate chemical reductants, including zero valent metals, palladium (Pd)
catalyst, and emulsified zero valent iron (EZVI), for dechlorination of PCBs in
the presence and absence of soil. In the absence of soil, Pd-catalyzed treatments
(Pd with electrolytic ZVI or iron/aluminum alloy) achieved rapid destruction of a
model PCB congener, 2-chlorobiphenyl, with half-lives ranging from 43 to 110 min.
For treatment of soils containing Aroclor 1248 at an initial concentration of
approximately 1,500 mg kg(-1), Pd-catalyzed treatments achieved no measurable
enhancement over the background PCB depletion rate (i.e., that measured in the
untreated control) of 5.3 mg kg(-1)week(-1). In the presence of soils, EZVI was
the only approach evaluated that resulted in a clear enhancement in PCB
dechlorination rates. EZVI achieved PCB concentration reductions of greater than
50% at an average rate of 19 mg kg(-1)week(-1). The results suggest that slow PCB
desorption limits treatment effectiveness in soils.
PMID- 25113194
TI - Occurrence and possible sources of organochlorine pesticides (OCPs) and
polychlorinated biphenyls (PCBs) along the Chao River, China.
AB - To analyze the possible influence of organochlorine pesticides (OCPs) and
polychlorinated biphenyls (PCBs) on Miyun Reservoir, 14 soil samples and 1 water
sample were collected along the Chao River, which is the main upstream source of
the reservoir. A total of 24 kinds of OCPs and 12 kinds of dioxin-like PCBs were
measured. Results showed that the ?OCPs concentration ranged from 0.8145 to
16.8524 ng g(-1), and the ?PCBs ranged from 0.0039 to 0.0365 ng g(-1).
Dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexanes (HCHs) and
hexachlorobenzene (HCB) were the three dominant kinds of OCPs in this region, and
the majority component of the PCBs was PCB-118 in both water and soil samples.
The OCP ratios suggest that new inputs of lindane exist. DDTs mainly come from
old technical inputs. HCHs might come from a new application of lindane, which
highlights the importance of prohibited pesticide control. OCP concentrations
were higher in corn fields and orchards and lower in forest lands and grasslands,
which indicated that OCPs were very much influenced by human activities. The
proportion of PCB components in this study area suggested that they mainly came
from atmospheric deposition.
PMID- 25113196
TI - Polychlorinated dibenzo-p-dioxins and dibenzofurans in water and six fish species
from Dongting Lake, China.
AB - There have been few studies of polychlorinated dibenzo-p-dioxins and
dibenzofurans (PCDD/Fs) in environmental water because of the large volume of
water required for PCDD/Fs analysis. Water quality directly affects aquatic
organisms, and little is known about how PCDD/Fs are transported in aquatic
environments. PCDD/Fs were analyzed in eight water samples from Dongting Lake,
China, which was contaminated with PCDD/Fs because of sodium pentachlorophenate
use between the 1960s and the 1980s. The total PCDD/F concentrations in the
samples were 36-345 pg L(-1), and the mean was 191 pg L(-1). Octachlorodibenzo-p
dioxin was the most abundant PCDD/F congener in every sample, contributing 67-95%
of the total 2,3,7,8-chlorinated PCDD/F concentrations. The toxic equivalent (WHO
TEQ) concentrations in the samples were 0.17-0.37 pg L(-1), and the mean was 0.28
pg L(-1), which is higher than the Canadian environmental quality guideline
(0.038 pg L(-1) WHO-TEQ for freshwater) and the United States Environmental
Protection Agency water quality criterion (0.014 pg L(-1) WHO-TEQ). PCDD/Fs were
also determined in six fish species collected from Dongting Lake, to assess the
concentrations, accumulation patterns, and potential for toxic effects. The total
2,3,7,8-chlorinated PCDD/F concentrations in the fish samples were 2.2-17.9 pg g(
1) (wet weight), and the dominant congeners were octachlorodibenzo-p-dioxin,
1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, 1,2,3,4,7,8-hexachlorodibenzo-p
dioxin, and 2,3,4,7,8-pentachlorodibenzofuran. The PCDD/F WHO-TEQs were 0.10-0.92
ww (3.3-65.3l w) pg g(-1) in different species of fish. PCDD/F congener patterns
in fish may be affected by food chain biomagnification and the lipid content of
the species.
PMID- 25113198
TI - Time trends and congener profiles of PCDD/Fs, PCBs, and PBDEs in Baltic herring
off the coast of Finland during 1978-2009.
AB - In Finland, consumption of Baltic fatty fish may lead to high exposure to
persistent organic pollutants (POPs), which might have hazardous health effects.
Monitoring of POPs in Baltic fish enables the health authorities to keep dietary
advice on fish consumption up to date. In this study, which is a compilation of
analytical data from earlier studies, time trends and congener profiles of
polychlorinated dioxins and furans (PCDD/Fs) and biphenyls (PCBs), and
polybrominated diphenyl ethers (PBDEs) in Baltic herring are reported. Altogether
344 samples of Baltic herring from 1978-2009 were collected across the Finnish
coast of the Baltic Sea. The chemical analysis was performed in an accredited
testing laboratory with high resolution gas chromatography mass spectrometry.
During the 31-year period, PCDD/F and PCB concentrations decreased on
approximately 80%, from approximately 20 to 5 pg/g fw, expressed as WHO2005 TEQ.
The PBDE concentrations experienced a 4-10 fold increase during late 1980s-early
1990s, and declined to 1978s levels of approximately 2 ng/g fw by 2009. The
current concentrations of PCDD/Fs, PCBs and PBDEs in Baltic herring are
relatively low, and mostly below EU maximum accepted levels, and are expected to
continue decreasing. In the future, it may be possible to re-evaluate the
consumption restrictions for this specific Baltic fatty fish.
PMID- 25113197
TI - Releases of chlorobenzenes, chlorophenols and dioxins during fireworks.
AB - In fireworks, organic additives with high chlorine content such as
hexachlorobenzene (HCB) are used for the improvement of illumination effects. In
the course of a monitoring campaign for the detection of HCB in fireworks,
atmospheric concentrations of chlorobenzenes (CBs), chlorophenols (CPs) and
polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), were measured
during the Swiss National holiday August 1, 2011 which is celebrated with
fireworks nationwide. Samples were collected in the city of Zurich using high
volume air samplers equipped with quartz fiber filters and poly-urethane foam
plugs. With one sampling period of 3h, a peak HCB concentration of 297 pg m(-3)
was detected. Maximum total concentrations of pentachlorophenol and PCDD/Fs were
218 pg m(-3) and 61 fg I-TEQ m(-3), respectively. These levels are in the order
of ten times above background concentrations measured one week before and two
weeks after the event. Atmospheric emissions of HCB and CPs were quantified using
a multimedia mass balance model to interpret the field measurements resulting in
total emissions of HCB and CPs during the event of 23 g and 25 g, respectively.
Based on per capita amounts this corresponds to total annual emissions from
fireworks of 1.5 kg for each of the two pollutants in Switzerland. Starting from
an estimation of the total worldwide emissions of HCB, in Switzerland emissions
from fireworks may represent about 2-14% of total HCB releases.
PMID- 25113199
TI - PCDD/Fs, PCBs and PBDEs in zooplankton in the Baltic Sea - spatial and temporal
shifts in the congener-specific concentrations.
AB - In the marine food-webs, zooplankton is a key element in the transfer of
persistent organic pollutants to higher trophic levels. We determined the
congener-specific concentrations of polychlorinated dibenzo-p-dioxins (PCDDs),
polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs) and
polybrominated diphenyl ethers (PBDEs) in offshore zooplankton (size from 0.2 to
20mm) collected in 2001, 2002 and 2010 in the northern and central Baltic Sea. Of
the PCDD/Fs, the concentrations of 2378-TCDF were from 18 to 47 and of 23478
PeCDF from 7.9 to 29 pg g(-1)fat and showed little temporal differences. However,
1234678-HpCDF and OCDF were abundant in 2001-2002 especially in the eastern Gulf
of Finland (average concentrations 50 and 89 pg g(-1)fat, respectively). In 2010
the concentrations of these two congeners were lower, 29 and 30 pg g(-1)fat,
respectively, but still substantially higher than in the other surveyed areas.
The principal components analysis (PCA) supported that area-specific patterns in
pollution strongly contributed to the congener profiles particularly in surface
sediment and in sediment trap material, but even in zooplankton. The
concentrations of the PCBs were highest in the Gulf of Finland and in the
Bothnian Bay. The concentrations of most PCBs were somewhat lower in 2010 than in
2001-2002. Of the dioxin-like PCBs, the concentrations of PCB-77 were highest
(271-572 pg g(-1)fat) but PCB-126 (32-113 pg g(-1)fat) contributed from 85% to
91% of the total toxicity of PCBs due to its higher toxic potency. Of the PBDEs,
the BDE47 and BDE99 were the most abundant (concentrations from 1.2 to 4.6 and
from 0.4 to 3.3 ng g(-1) fat, respectively). The concentrations of most PBDEs
were lower in 2010 than in 2001/2002 except in the eastern Gulf of Finland.
PMID- 25113200
TI - Fish consumption as a source of human exposure to perfluorinated alkyl substances
in Italy: analysis of two edible fish from Lake Maggiore.
AB - Extensive screening analyses of perfluorooctane sulfonate and related
perfluorinated compounds (PFCs) in biota samples from all over the world have
identified PFCs as global pollutants and have shown their bioaccumulation into
higher trophic levels in the food chain. Perfluorooctanoic acid (PFOA) and
perfluorooctane sulfonate (PFOS) are environmental contaminants belonging to a
chemical group known as perfluorinated compounds. PFOS and PFOA are very
persistent in the environment and bioaccumulate in humans. They are potential
reproductive and developmental toxicants and are considered to be emerging
endocrine disrupters. The United States Environmental Protection Agency (USEPA)
considers both compounds to be carcinogenic and the European Food Safety
Authority (EFSA) recently pointed out that they are associated with adverse
health effects. Diet is considered the main source of exposure to PFCs, which
have been found more frequently in fish and other seafood, compared to other food
groups. In fact, aquatic ecosystems represent the final reservoir for PFCs due to
their great affinity for sedimentary and living organic matter. In these systems,
measured levels of persistent organic pollutants (POPs) could increase along the
trophic web, ultimately affecting humans that consume aquatic species. In this
study, PFOS and PFOA was detected by LC-MS/MS in muscle samples of Coregonus
lavaretus (European whitefish) and Perca fluviatilis (European perch) collected
from Lake Maggiore, a large lake located on the south side of the Italian Alps.
PFOA was not found in any of the investigated samples above the limit of
quantitation of 0.50 ng g(-1) fresh weight (fw), whereas PFOS was detected in all
90 samples with concentrations of up to 46.0 ng g(-1)fw. Mean concentrations were
22.2 ng g(-1)fw in P. fluviatilis and 20.0 ng g(-1)fw in C.lavaretus. Comparison
of our results with literature data on PFOS intake suggested that fish from Lake
Maggiore may be a significant source of dietary PFOS exposure, even if the
reported values were lower than the Total Daily Intake (TDI) proposed by EFSA.
PMID- 25113201
TI - Estimating stepwise debromination pathways of polybrominated diphenyl ethers with
an analogue Markov Chain Monte Carlo algorithm.
AB - A stochastic process was developed to simulate the stepwise debromination
pathways for polybrominated diphenyl ethers (PBDEs). The stochastic process uses
an analogue Markov Chain Monte Carlo (AMCMC) algorithm to generate PBDE
debromination profiles. The acceptance or rejection of the randomly drawn
stepwise debromination reactions was determined by a maximum likelihood function.
The experimental observations at certain time points were used as target
profiles; therefore, the stochastic processes are capable of presenting the
effects of reaction conditions on the selection of debromination pathways. The
application of the model is illustrated by adopting the experimental results of
decabromodiphenyl ether (BDE209) in hexane exposed to sunlight. Inferences that
were not obvious from experimental data were suggested by model simulations. For
example, BDE206 has much higher accumulation at the first 30 min of sunlight
exposure. By contrast, model simulation suggests that, BDE206 and BDE207 had
comparable yields from BDE209. The reason for the higher BDE206 level is that
BDE207 has the highest depletion in producing octa products. Compared to a
previous version of the stochastic model based on stochastic reaction sequences
(SRS), the AMCMC approach was determined to be more efficient and robust. Due to
the feature of only requiring experimental observations as input, the AMCMC model
is expected to be applicable to a wide range of PBDE debromination processes,
e.g. microbial, photolytic, or joint effects in natural environments.
PMID- 25113202
TI - Identifying the provenance of Leach's storm petrels in the North Atlantic using
polychlorinated biphenyl signatures derived from comprehensive two-dimensional
gas chromatography with time-of-flight mass spectrometry.
AB - PCB signatures can be used for source identification, exposure studies, age
dating and bio-monitoring. This study uses comprehensive two-dimensional gas
chromatography with time-of-flight mass spectrometry (GCxGC-ToFMS) to produce a
PCB signature comprised of over 80 PCBs for individual Leach's storm petrels
(Oceanodroma leucorhoa). The Leach's storm petrel is a relatively small, elusive,
understudied pelagic bird, which only returns to remote islands under darkness
during the breeding season. Samples were obtained from 25 Leach's storm petrels
found dead in Canada and the UK following storm events in 2006 and 2009. Tissue
samples were extracted and analysed by GCxGC-ToFMS and results showed that 83 PCB
congeners were present in >60% of samples. An assessment of the PCB signature in
four different tissue types showed that it did not vary greatly in samples
obtained from the gut, heart, liver and stomach. Multivariate statistical
analysis identified a distinctive PCB signature in birds from Canada and Europe
which was used to identify the regional provenance and transatlantic movement of
individual birds. The findings showcase the ability of GCxGC-ToFMS to provide the
high quality congener specific analysis that is necessary for PCB fingerprinting,
as well as highlighting the potential of PCB signatures for use in ecological
studies of movement, foraging and behaviour.
PMID- 25113203
TI - Historical trends of inorganic and organic fluorine in sediments of Lake
Michigan.
AB - Total fluorine (TF), extractable organic fluorine (EOF) and poly- and per
fluorinated compounds (PFCs) were measured in eight dated cores of sediment taken
along with 27 surface sediments from Lake Michigan in 2010. Based on rates of
sedimentation, total concentrations of PFCs (?PFCs) reached a maximum in the
later 1990s and early 2000s. This result is consistent with rapid changes in
production and subsequent sedimentation. Perfluorooctanesulfonate (PFOS) and
perfluorooctanoate (PFOA) are still the predominant PFCs in the cores, but in
surface sediments, concentrations of perfluorobutane sulfonate (PFBS) and
perfluorobutanoic acid (PFBA) are now occurring at concentrations comparable to
those of PFOS and PFOA. This observation is consistent with shifts in patterns of
production and use in the US and Canada. Concentrations of TF in sediments were
greater than those of EOF. This result is consistent with a larger proportion of
un-extractable fluorinated material in both surface sediments and in cores.
PMID- 25113204
TI - Polychlorinated biphenyls in respirable particulate matter from different
industrial areas in northern China.
AB - As two typical industrial bases of China's great metropolises, Lingfen and Datong
are affected by the steel industry, chemical plants, coal-fired power plants, and
several coking plants, and face pollution from polychlorinated biphenyls (PCBs).
Therefore, this study was conducted to determine the PCB concentrations in PM2.5
and PM2.5-10 samples obtained in Lingfen and Datong. We collected 22 respirable
particulate matter samples (11 of PM2.5 and 11 of PM2.5-10) from Lingfen and
Datong, and measured a total of 144 PCB congeners. The total PCB concentrations
were 5.92-38.7 pg m(-3) (median: 21.58 pg m(-3)) in PM2.5 and 1.83-40.8 pg m(-3)
(median: 24.3 pg m(-3)) in PM2.5-10 in Linfen, and 4.33-18.5 pg m(-3) (median:
11.9 pg m(-3)) in PM2.5 and 13.0-47.4 pg m(-3) (median: 17.4 pg m(-3)) in PM2.5
10 in Datong. Of the PCB homologues, the dominant PCBs detected in the various
media were all trichlorobiphenyls (tri-CBs). Moreover, the PCB distributions in
PM2.5 and PM2.5-10 samples were quite different in the two cities. This may be
caused by the differences of the industrial structures, and their relatively
unintentional release of PCBs in these cities. Source analysis revealed that the
major PCB contaminants in Linfen and Datong were tri-CBs and di-CBs, which were
possibly associated with unintentional release of PCBs. Toxic equivalency
concentrations based on ten dioxin-like PCBs ranged from 4.0*10(-5) to 2.3*10(-3)
pgWHO-TEQ m(-3) in Linfen, and 4.5*10(-4) to 2.6*10(-4) pgWHO-TEQ m(-3) in
Datong. The presence of PCB pollution is a potential threat to the residents of
Datong and Linfen.
PMID- 25113206
TI - Inhibition of the de novo synthesis of PCDD/Fs on model fly ash by sludge drying
gases.
AB - Sludge drying gases (SDG), evolving from drying and mild thermal decomposition
(<300 degrees C) of raw sewage sludge contain NH3 and SO2 as well as other N- and
S-compounds. All of these are potential PCDD/Fs suppressants. It is indeed
observed that these SDG suppress 2,3,7,8-substitued PCDD/Fs formation on Model
Fly Ash (MFA) with an efficiency up to 97.6% in wt. units and 96% in I-TEQ,
respectively. This suppression is strong for (the bulk of) PCDD/Fs, adsorbed on
the model fly ash; conversely, sludge drying gases enhance PCDD/Fs desorption
from MFA. Moreover, TCDD/Fs are suppressed least, possibly following stepwise
dechlorination of higher chlorinated PCDD/Fs. Characteristics, such as the type,
origins and amount of sludge, its moisture-, nitrogen- and sulfur content and the
nature of the thermal treatment applied are all expected to influence upon the
suppression capabilities. In this study three types of dry sludge are tested and
applied as suppressant in four different amounts or modes. The quality of the
sludge drying gases is continuously monitored: the Gasmet results reveal that NH3
and SO2 are the most important components of SDG. The MFA reaction residue is
scrutinized by Scanning Electron Microscope (SEM) and Energy Dispersive
Spectrometer (EDS) analysis. A large number of particles attaching to the surface
of model fly ash are observed by SEM. Moreover, EDS analysis reveals that part of
the chlorine in MFA is carried away with the SDG and replaced by sulfur, so that
eliminating chlorine may be part of the inhibition mechanism. However, further
research is still needed to establish the optimum operating modes and to confirm
the role of both inorganic and organic nitrogen and sulfur compounds in the
suppression of PCDD/Fs formation on model fly ash.
PMID- 25113205
TI - Adjusting serum concentrations of organochlorine compounds by lipids and
symptoms: a causal framework for the association with K-ras mutations in
pancreatic cancer.
AB - In clinically aggressive diseases, patients experience pathophysiological changes
that often alter concentrations of lipids and environmental lipophilic factors;
such changes are related to disease signs and symptoms. The aim of the study was
to compare the effects of correcting for total serum lipids (TSL) and other
clinical factors on the odds of mutations in the K-ras oncogene by organochlorine
compounds (OCs), in logistic models, in 103 patients with exocrine pancreatic
cancer (EPC) using a causal directed acyclic graph (DAG) framework. Results and
likelihood of bias were discussed in the light of possible causal scenarios. The
odds of K-ras mutated EPC was associated with some TSL-corrected OCs, including
p,p'-DDT (p-value: 0.008) and polychlorinated biphenyl 138 (p-trend: 0.024). When
OCs were not corrected by TSL, the OR of a K-ras mutation was significant for
p,p'-DDT (p-trend: 0.035). Additionally adjusting for cholestatic syndrome
increased the ORs of TSL-corrected OCs. When models were adjusted by the interval
from first symptom to blood extraction (ISE), the ORs increased for both TSL
corrected and uncorrected OCs. Models with TSL-corrected OCs and adjusted for
cholestatic syndrome or ISE yielded the highest ORs. We show that DAGs clarify
the covariates necessary to minimize bias, and demonstrate scenarios under which
adjustment for TSL-corrected OCs and failure to adjust for symptoms or ISE may
induce bias. Models with TSL-uncorrected OCs may be biased too, and adjusting by
symptoms or ISE may not control such biases. Our findings may have implications
as well for studying environmental causes of other clinically aggressive
diseases.
PMID- 25113207
TI - Spatial and seasonal distribution of organochlorine pesticides in the sediments
of the Yangtze Estuary.
AB - The spatial and seasonal distribution of organochlorine pesticides (OCPs) in the
sediments of the Yangtze Estuary was investigated. The total concentration of 19
OCPs (?OCPs), including alpha-HCH, beta-HCH, gamma-HCH, delta-HCH, o, p'-DDE, p,
p'-DDE, o, p'-DDD, p, p'-DDD, o, p'-DDT, p, p'-DDT, heptachlor, aldrin,
heptachlor epoxide (Isomer B, Isomer A), endosulfan I, dieldrin, endrin,
endosulfan II and methoxychlor, in the surface sediments ranged from 0.4 to 82.1
ng g(-1) d.w. The mean values of the ?OCPs were 8.5 +/- 8.3 ng g(-1) d.w., 26.7
+/- 12.1 ng g(-1) d.w., 40.5 +/- 18.2 ng g(-1) d.w., and 13.0 +/- 11.2 ng g(-1)
d.w. for August 2010, November 2010, February 2011 and May 2011, respectively.
The highest concentration of OCPs was detected at the river-sea boundary because
of the intense resuspension and redeposition of sediments in this area. The OCPs
preferred to accumulate in the inner estuary, rather than in the offshore area in
the dry season, whereas the opposite occurred in the flood season. This
phenomenon was related to the seasonal changes of the Changjiang diluted water
(CDW). OCPs in the offshore area were controlled by the ocean currents and the
monsoon. There was a southward increase for the OCP deposition in the offshore
area in the winter. This increase resulted from the influences of the southward
Yellow Sea coastal current and the East China Sea coastal current, as well as the
northwest wind in winter. The Three Gorges Dam had an impact on HCH composition
by changing the sediment redistribution during the deposition process.
PMID- 25113208
TI - Sources, gastrointestinal absorption and stereo-selective and tissue-specific
accumulation of Dechlorane Plus (DP) in chicken.
AB - Dechlorane Plus (DP) isomers, along with two dechlorinated metabolites were
measured in environmental matrices, chyme and digestive tract contents and
tissues of chicken from an e-waste recycling site located in South China. Soil is
proved to be the main source of DP in chicken rather than food because soil
contributes more than 94% of total DP in chyme. In the gastrointestinal tract
absorption processes, no selective absorption was observed for DP isomers during
the ingestion processes. The tissue distribution of DP isomers in chicken
exhibits complicated characteristics. The lipid contents in tissues are the main
factors in the tissue distribution of DP, while the different blood perfusion
state and the different tissue functions also seem to influence the tissue
distribution of DP. The fat, brain, and liver exhibit higher fanti values (0.65,
0.64, and 0.64) than the other tissues (0.54-0.59). The elevated fanti values of
DP from the contamination source (0.52 in soil) to chicken suggest
stereoselective bioaccumulation of anti-DP in chicken. The similar ratios of anti
Cl11-DP to anti-DP between soil and chicken imply that anti-Cl11-DP mainly
derives from the uptake from environment rather than in vivo dechlorination.
PMID- 25113209
TI - Spatial distributions of methoxylated and hydroxylated polybrominated diphenyl
ethers in the East China Sea--a seaward increasing trend.
AB - Methoxylated (MeO-) and hydroxylated (OH-) polybrominated diphenyl ethers (PBDEs)
in marine environments have been of increasing concern due to their potential
ecological toxicities and worldwide occurrence. However, few reports have been
referred to their occurrence and distributions in marine sediments despite large
numbers of studies on marine organisms have been reported. In the present paper,
nine MeO-BDEs, ten OH-BDEs and three phytoplankton biomarkers (PBs) of
brassicasterol, dinosterol and alkenones have been measured in surface sediments
from the East China Sea. 6-MeO-BDE47, 2'-MeO-BDE68 and 6-OH-BDE47 were
predominant congeners, ranging from 5.2 to 599.5 pg g(-1)dw, 5.2 to 562.4 pg g(
1)dw, and 11.4 to 129.1 pg g(-1)dw, respectively. Their spatial patterns all
presented a seaward increasing trend and higher levels of these compounds were
mainly concentrated in the outer shelf influenced by the Kuroshio Current. The
patterns further prove that these ortho-substituted MeO-BDEs and OH-BDEs in
marine sediments are natural compounds. Furthermore, alkenones also presented a
seaward increasing trend. Statistical analysis shows that there are significant
correlations between MeO-BDEs, OH-BDEs and alkenones, impling the potential of
coccolithophorids for producing these natural compounds and their global
distribution, especially in open oceans. Comparison between TOC and the ratio of
6-MeO-BDE47/6-OH-BDE47 suggests that TOC should be a potential controlling factor
of the conversion between MeO-BDE and OH-BDE pairs.
PMID- 25113210
TI - Tea saponin enhanced biodegradation of decabromodiphenyl ether by Brevibacillus
brevis.
AB - Decabromodiphenyl ether (BDE209) is a ubiquitous persistent pollutant and has
contaminated the environment worldwide. To accelerate BDE209 elimination and
reveal the mechanism concerned, the biosurfactant tea saponin enhanced
degradation of BDE209 by Brevibacillus brevis was conducted. The results revealed
that tea saponin could efficiently increase the solubility of BDE209 in mineral
salts medium and improve its biodegradation. The degradation efficiency of 0.5 mg
L(-1) BDE209 by 1 g L(-1) biomass with surfactant was up to 55% within 5d.
Contact time was a significant factor for BDE209 biodegradation. BDE209
biodegradation was coupled with bioaccumulation, ion release and utilization, and
debromination to lower brominated PBDE metabolites. During the biodegradation
process, B. brevis metabolically released Na(+), NH4(+), NO2(-) and Cl(-), and
utilized the nutrient ions Mg(2+), PO4(3-) and SO4(2-). GC-MS analysis revealed
that the structure of BDE209 changed under the action of strain and
nonabromodiphenyl ethers (BDE-208, -207 and -206), octabromodiphenyl ethers (BDE
203, -197 and -196) and heptabromodiphenyl ether (BDE-183) were generated by
debromination.
PMID- 25113211
TI - Correlation between human maternal-fetal placental transfer and molecular weight
of PCB and dioxin congeners/isomers.
AB - Establishing methods for the assessment of fetal exposure to chemicals is
important for the prevention or prediction of the child's future disease risk. In
the present study, we aimed to determine the influence of molecular weight on the
likelihood of chemical transfer from mother to fetus via the placenta. The
correlation between molecular weight and placental transfer rates of
congeners/isomers of polychlorinated biphenyls (PCBs) and dioxins was examined.
Twenty-nine sample sets of maternal blood, umbilical cord, and umbilical cord
blood were used to measure PCB concentration, and 41 sample sets were used to
analyze dioxins. Placental transfer rates were calculated using the
concentrations of PCBs, dioxins, and their congeners/isomers within these sample
sets. Transfer rate correlated negatively with molecular weight for PCB
congeners, normalized using wet and lipid weights. The transfer rates of PCB or
dioxin congeners differed from those of total PCBs or dioxins. The transfer rate
for dioxin congeners did not always correlate significantly with molecular
weight, perhaps because of the small sample size or other factors. Further
improvement of the analytical methods for dioxin congeners is required. The
findings of the present study suggested that PCBs, dioxins, or their congeners
with lower molecular weights are more likely to be transferred from mother to
fetus via the placenta. Consideration of chemical molecular weight and transfer
rate could therefore contribute to the assessment of fetal exposure.
PMID- 25113212
TI - Levels of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/Fs) and dioxin
like PCBs in free range eggs from Vietnam, including potential health risks.
AB - Chicken and duck eggs collected from three different areas in Vietnam were
examined for polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). These
regions included a background area, an area sprayed with Agent Orange and the
Bien Hoa airbase area where Agent Orange was handled by the US Army. The latter
area now is inhabited and people keep their own laying hens. Egg samples were
first screened with an in vitro reporter gene bioassay and a selection was
analyzed by GC/HRMS. Samples from Bien Hoa airbase showed very high PCDD/F
levels, up to 249 pg dioxin-equivalents (TEQ)/g fat, mainly due to 2,3,7,8
tetrachlorodibenzo-p-dioxin (TCDD). In the sprayed areas, levels (3.2-8.2 pg TEQ
g(-1)) were comparable to those observed in background areas (3.2-8.2 pg TEQ g(
1) fat). The estimated average consumption of 22 g d(-1) of the highly
contaminated eggs will result in a 2-fold exceedance of the current exposure
limits for adults and 5-fold for children, even without considering other
contaminated food sources. This indicates a potential health risk from
consumption of these highly contaminated eggs, which were not yet considered as a
source for exposure to PCDD/Fs of people living in the highly contaminated areas.
PMID- 25113213
TI - Kinetic study of chlordecone orally given to laying hens (Gallus domesticus).
AB - The former use of chlordecone (CLD) in the French West Indies has resulted in
long-term pollution of soils. In this area, CLD may be transferred into eggs of
hens reared outdoors, through soil ingestion. In order to assess this risk, a
kinetic study involving the contamination of laying hens (22 weeks of age) with a
diet containing 500 MUg CLD kg(-1) during 42 d, followed by a depuration period
of 35 d was carried out. Forty-four hens were sequentially slaughtered all over
the experimental period and their liver, egg, abdominal fat and serum were
collected. Two additional edible tissues, pectoral and leg muscles, were
collected in hens slaughtered at the end of the contamination period. The
depuration half-life of CLD in liver, egg, abdominal fat and serum was estimated
at 5.0 +/- 0.38 (mean +/- SE), 5.5 +/- 0.29, 5.3 +/- 0.37 and 5.1 +/- 0.66 d,
respectively. CLD concentration at the end of the contamination period reached
1640 +/- 274, 460 +/- 41, 331 +/- 23, and 213 +/- 8.5 MUg kg(-1) fresh matter
(FM), respectively. The corresponding concentrations in pectoral and leg muscles
were 119 +/- 8.4, 127 +/- 11 MUg kg(-1) FM, respectively. The steady state carry
over rate of CLD in eggs reached 43 +/- 7.6%. This experiment demonstrates the
preferential accumulation of CLD in liver, its significant transfer to eggs and
its quite short half-life. It is concluded that raising hens on even mildly
contaminated areas would lead to products exceeding the regulatory maximum
residue limit of 20 MUg CLD kg(-1).
PMID- 25113214
TI - The occurrence of organic contaminants in European eel (Anguilla anguilla) in
Poland: an environmental quality assessment.
AB - The objective of the present study was to provide information on the levels of
pollutants in the tissues of eels caught in Polish waters. The contaminants
included in the study are those which have not yet been widely studied in eel
stocks, but which arouse concern in relation to the environment. An overview of
the pollutant levels in eels caught in other European waters was also conducted.
The results are evaluated in terms of environmental quality and consumer health.
The mean concentrations of SigmaPBDEs and SigmaHBCDs in muscles of eels sampled
in Polish waters were between 1 and 2 ng g(-1) ww. The mean TBT concentrations
were between 2 and 4 ng g(-1)ww with the exception of samples from the Szczecin
Lagoon, in which the mean TBT concentration was about tenfold higher.
PMID- 25113215
TI - Polychlorinated biphenyls (PCBs) and p,p'-dichlorodiphenyldichloroethylene (DDE)
concentrations in maternal and umbilical cord serum in a human cohort from South
Portugal.
AB - Organochlorine compounds as polychlorinated biphenyls (PCBs) and pp'
dichlorodiphenyldichloroethylene (pp'DDE) are ubiquitous, resistant to
degradation and lipophilic compounds, commonly found in the general population.
Prenatal exposure to these compounds has been associated to adverse developmental
effects. Levels of PCBs and pp'DDE were investigated in maternal and umbilical
cord serum of 68 women/newborns pairs from Algarve, South Portugal. Mean sum PCBs
congeners and pp'DDE concentrations were 1.62 +/- 0.39 ng mL(-1)and 1.11 +/- 0.69
ng mL(-1)-for maternal and 1.45 +/- 0.25 ng mL(-1) and 0.85 +/- 0.50 ng mL(-1)for
cord serum, respectively. Congeners distribution pattern followed the order PCB
153>180>130, both for maternal and cord serum). Significant correlations (p<0.05)
were found between maternal and cord serum concentrations. The umbilical
cord/maternal serum ratio were 0.90 and 0.76, respectively for SigmaPCB and
pp'DDE Multivariate analyses relate women in urban centers with higher PCB
levels, while higher pp'DDE relates to older primiparous women that live at rural
areas. PCBs were also correlated to more portions of fat rich foods, while pp'DDE
is associated to higher ingestion of vegetables and fruits. Smoking habits only
correlated to maternal PCB. The present work provides, to our knowledge and for
the first time, baseline human-biomonitoring data and establishes background
ranges of PCB and pp'DDE levels in the maternal and umbilical cord serum in the
Algarve region. These compounds exhibited the capacity to pass the placenta
barrier and target the fetus. Even in non-industrialized areas, and in non
intensive agriculture areas, like the Southern Portugal, there is a need to take
measures to eliminate or minimize the risk of organochlorine exposure during
pregnancy.
PMID- 25113216
TI - Influence of persistent organic pollutants on oxidative stress in population
based samples.
AB - Persistent organic pollutants (POPs) are a large group of chemicals widely used
and produced in various industrial applications. Many cell culture/animal studies
have shown that POPs can induce oxidative stress. Since such data is lacking in
humans, we conducted a large population-based study to analyze associations
between POPs and oxidative stress markers. We measured following POPs; 16
polychlorinated biphenyls (PCBs), 5 organochlorine (OC) pesticides,
octachlorinated dibenzo-p-dioxin, and polybrominated diphenyl ether 47, and
oxidative stress markers; homocysteine, reduced [GSH] and oxidized glutathione
[GSSG], glutathione ratio [GSSG/GSH], total glutathione, oxidized low-density
lipoprotein [ox-LDL], ox-LDL antibodies, conjugated dienes, baseline conjugated
dienes of LDL, and total anti-oxidative capacity in plasma samples collected from
992 70-year old individuals (50% women) from the population-based Prospective
Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. Linear
regression analyses were performed to study the associations between oxidative
stress markers and summary measures of POPs including the total toxic equivalence
(TEQ), sums of PCBs and OC pesticides (main exposures) while adjusting for
potential confounders. In multivariable-adjusted analyses, sum of PCBs showed
strong associations with ox-LDL (beta=0.94; P=2.9*10(-6)). Further, sum of PCBs
showed association with glutathione-related markers (GSSG: beta=-0.01; P=6.0*10(
7); GSSG/GSH: beta=-0.002; P=9.7*10(-10)), although in reverse direction. Other
summary measures did not show any significant association with these markers. In
our study of elderly individuals from the general population, we show that plasma
levels of POPs are associated with markers of increased oxidative stress thereby
suggesting that even low dose background exposure to POPs may be involved in
oxidative stress.
PMID- 25113217
TI - Sorption behaviors of a persistent toxaphene congener on marine sediments under
different physicochemical conditions.
AB - Sorptive processes are important parameters affecting the mobility, availability
and fate of persistent organic pollutants (POPs), such as toxaphene, in aquatic
systems. The sorption and desorption behaviors of the B7-1450, a stable toxaphene
congener in environment, on marine sediment was studied under different
temperature and salinity conditions to better understand the B-1450 distribution
in estuarine systems. The data were fitted to different sorption models to
characterize sorption behaviors by evaluating sorption coefficients and
sequestrated fraction of B7-1450 on sediments. High carbon-normalized sorption
coefficients (Koc) of the B7-1450 were observed with values ranging from 3.2*104
to 6.0*104 mL g(-1) under experimental conditions. The data showed an increase of
B7-1450 sorption coefficients with the salinity and a decrease with temperature.
These investigations indicate that B7-1450 is three times more sequestred on
sediments in cold (2 degrees C, 30 psu) than in warm marine conditions (20
degrees C, 30 psu). These results suggest that the mobility and bioavailable of
B7-1450 or other POPs from the sediments could be less important in cold marine
comparatively in warm marine and warm freshwater media. As a result of climate
changes, the warming of mid and high latitudes coastal waters could enhance the
mobility of POPs.
PMID- 25113218
TI - Spatial and seasonal distributions of polychlorinated dibenzo-p-dioxins and
dibenzofurans and polychlorinated biphenyls around a municipal solid waste
incinerator, determined using polyurethane foam passive air samplers.
AB - Twenty-six ambient air samples were collected around a municipal solid waste
incinerator (MSWI) in the summer and winter using polyurethane foam passive air
samplers, and analyzed to assess the spatial and seasonal distributions of
polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated
biphenyls (PCBs). Three stack gas samples were also collected and analyzed to
determine PCDD/F (971 pg m(-3) in average) and PCB (2,671 pg m(-3) in average)
emissions from the MSWI and to help identify the sources of the pollutants in the
ambient air. The total PCDD/F concentrations in the ambient air samples were
lower in the summer (472-1,223 fg m(-3)) than the winter (561-3913 fg m(-3)). In
contrast, the atmospheric total PCB concentrations were higher in the summer (716
4,902 fg m(-3)) than the winter (489-2,298 fg m(-3)). Principal component
analysis showed that, besides emissions from the MSWI, the domestic burning of
coal and wood also contributed to the presence of PCDD/Fs and PCBs in the ambient
air. The PCDD/F and PCB spatial distributions were analyzed using ordinary
Kriging Interpolation and limited effect was found to be caused by emissions from
the MSWI. Higher PCDD/F and PCB concentrations were observed downwind of the MSWI
than in the other directions, but the highest concentrations were not to be found
in the direction with the greatest wind frequency which might be caused by
emissions from domestic coal and wood burning. We used a systemic method
including sampling and data analysis method which can provide pioneering
information for characterizing risks and assessing uncertainty of PCDD/Fs and
PCBs in the ambient air around MSWIs in China.
PMID- 25113220
TI - Gender differences in alcohol demand: a systematic review of the role of prices
and taxes. Comment on conclusions by Nelson.
PMID- 25113219
TI - Determination of organochlorines, polychlorinated biphenyls and polybrominated
diphenyl ethers in human hair: estimation of external and internal exposure.
AB - A novel method was developed for the analysis of organochlorine pesticides
(OCPs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers
(PBDEs) in human hair samples. External contaminants of hair were extracted with
acetone under sonication, while washed hair was further hydrolyzed in formic acid
and acetone (1:4, v/v) with microwave assisted extraction (MAE) for internal
contaminant measurements. Both internal and external extracts were cleaned up
with gel permeation chromatography (GPC) and then solid phase extraction (SPE),
before analyzed by a large volume injection-gas chromatography-tandem mass
spectrometry (LVI-GC-MS/MS) using triple quadruple mass analyzer. Good linearity
(R(2)? 0.996) was established within a concentration range between 0.1 and 100 ng
mL(-)(1) among all target analytes. The method was validated for accuracy,
precision and sensitivity. The developed method is intended to be cost effective
and robust for the routine human hair analysis of PCBs, PBDEs and OCPs including
acid-labile OCPs. The described method has been applied in pilot biomonitoring
study and the preliminary data suggested that the contaminant profiles with the
use of partial least-squares analysis discriminant analysis (PLA-DA) could be
useful in differentiating external and internal exposure.
PMID- 25113221
TI - The reaction enthalpy of hydrogen dissociation calculated with the Small System
Method from simulation of molecular fluctuations.
AB - We show how we can find the enthalpy of a chemical reaction under non-ideal
conditions using the Small System Method to sample molecular dynamics simulation
data for fluctuating variables. This method, created with Hill's thermodynamic
analysis, is used to find properties in the thermodynamic limit, such as
thermodynamic correction factors, partial enthalpies, volumes, heat capacities
and compressibility. The values in the thermodynamic limit at (T,V, MUj) are then
easily transformed into other ensembles, (T,V,Nj) and (T,P,Nj), where the last
ensemble gives the partial molar properties which are of interest to chemists.
The dissociation of hydrogen from molecules to atoms was used as a convenient
model system. Molecular dynamics simulations were performed with three densities;
rho = 0.0052 g cm(-3) (gas), rho = 0.0191 g cm(-3) (compressed gas) and rho =
0.0695 g cm(-3) (liquid), and temperatures in the range; T = 3640-20,800 K. The
enthalpy of reaction was observed to follow a quadratic trend as a function of
temperature for all densities. The enthalpy of reaction was observed to only have
a small pressure dependence. With a reference point close to an ideal state (T =
3640 K and rho = 0.0052 g cm(-3)), we were able to calculate the thermodynamic
equilibrium constant, and thus the deviation from ideal conditions for the lowest
density. We found the thermodynamic equilibrium constant to increase with
increasing temperature, and to have a negligible pressure dependence. Taking the
enthalpy variation into account in the calculation of the thermodynamic
equilibrium constant, we found the ratio of activity coefficients to be in the
order of 0.7-1.0 for the lowest density, indicating repulsive forces between H
and H2. This study shows that the compressed gas- and liquid density values at
higher temperatures are far from those calculated under ideal conditions. It is
important to have a method that can give access to partial molar properties,
independent of the ideality of the reacting mixture. Our results show how this
can be achieved with the use of the Small System Method.
PMID- 25113222
TI - Systematic review of diplommatinid land snails (Caenogastropoda, Diplommatinidae)
endemic to the Palau Islands. (1) Generic classification and revision of
Hungerfordia species with highly developed axial ribs.
AB - Diplommatinidae is a family of terrestrial caenogastropod snails that shows
extensive species diversity and endemic radiation within the Palau (Belau)
Islands. In this paper, we revised the taxonomy of Palauan endemic diplommatinids
based on the comparative morphology of shell, operculum, radula, and genitalia.
Although the generic classification of Palauan diplommatinids has been confusing,
they are currently classified into two genera, Hungerfordia Beddome, 1889 and
Palaina Semper, 1865. Palauan diplommatinids of these two genera are primarily
distinguished by the radular, genital and operculum morphology. However, shell
morphology, on which taxonomy has traditionally been based, does not provide
definitive characters for generic identification, because shell shape and
sculpture are highly variable within each genus. Although Hungerfordia has long
been known as a monotypic genus, the current study redefines the endemic genus to
include a wider range of species that were formerly placed in Diplommatina or
Palaina. Following species are transferred to Hungerfordia: H. alata (Crosse,
1866) comb. nov.; H. lamellata (Crosse, 1866) comb. nov.; H. pyramis (Crosse,
1866) comb. nov.; H. ringens (Crosse, 1866) comb. nov.; H. polymorpha (Crosse,
1866) comb. nov.; H. inflatula (Crosse, 1866) comb. nov.; H. lutea (Beddome,
1889) comb. nov.; H. aurea (Beddome, 1889) comb. nov.; H. gibboni (Beddome, 1889)
comb. nov.; H. crassilabris (Beddome, 1889) comb. nov. Pseudopalaina Moellendorff
in Kobelt & Moellendorff, 1898 (synonym nov.) is demoted as a junior synonym of
Hungerfordia. Palaina is also redefined based on the internal shell features and
operculum morphology, in addition to the external shell characters. Furthermore,
Eupalaina Kobelt & Moellendorff, 1898 is restored as a subgenus of Palaina for
Palauan species on the basis of a genital character. The taxonomy of Hungerfordia
species with highly developed axial ribs is revised. H. pelewensis Beddome, 1889,
H. lamellata (Crosse, 1866) comb. nov., and H. alata (Crosse, 1866) comb. nov.
are redescribed with new morphological data. Following new taxa are described: H.
triplochilus sp. nov., H. expansilabris sp. nov., H. nudicollum sp. nov., H.
echinata echinata sp. et subsp. nov., H. echinata tubulispina subsp. nov., H.
elegantissima sp. nov., H. goniobasis goniobasis sp. et subsp. nov., H.
goniobasis dmasechensis subsp. nov., H. subalata sp. nov., H. pteropurpuroides
sp. nov., H. papilio papilio sp. et subsp. nov., H. papilio stenoptera subsp.
nov..
PMID- 25113223
TI - Twelve new Demospongiae (Porifera) from Chilean fjords, with remarks upon sponge
derived biogeographic compartments in the SE Pacific.
AB - This article reports on 12 new species originating from the Chilean fjords
region, namely Clathria (Microciona) mytilifila sp. nov., Haliclona (Reniera)
caduca sp. nov., Latrunculia (L.) ciruela sp. nov., Latrunculia (L.) copihuensis
sp. nov., Latrunculia (L.) verenae sp. nov., Latrunculia (L.) yepayek sp. nov.,
Myxilla (Burtonanchora) araucana sp. nov., Neopodospongia tupecomareni sp. nov.,
Oceanapia guaiteca sp. nov., Oceanapia spinisphaera sp. nov., Suberites cranium
sp. nov. and Tethya melinka sp. nov. The material studied was collected between 5
and 30 m depth at latitudes comprised between 42o and 50oS, and is part of a
large collection of Chilean sponges gathered by an international team in a series
of expeditions. Identification keys are provided for SE Pacific Suberites and
Latrunculia, and the known species of Myxilla (Burtonanchora) and Neopodospongia.
A trans-Pacific link to the New Zealand fauna was retrieved for the latter genus.
Distribution ranges apparent from the materials studied here are judged too
preliminary to allow any inference on biotic boundaries in the SE Pacific. A
revision of earlier assertions about these biogeographic units and their
boundaries concluded that very little support remains other than for existence of
a Magellanic fauna. This is in part a consequence of revising the taxonomy of
sponge species originally deemed to underpin these areas. Specifically, the
former proposal of a Central to Southern Chile biogeographic unit (33-56oS) has
been markedly undone.
PMID- 25113224
TI - [Delayed anaphylaxis after ingestion of meat. Carbohydrate epitope galactose
alpha-1,3-galactose as cause of severe anaphylactic reactions].
AB - The correlation between anaphylaxis after consumption of meat and the
carbohydrate epitope galactose-alpha-1,3-galactose (alpha-Gal) was first
described in oncologic patients treated with cetuximab. An association with tick
bites and parasitosis is suspected. We report on a healthy patient who developed
sudden anaphylactic reactions after the ingestion of meat. Serologic and skin
tests confirmed sensitization to alpha-Gal. Avoiding the consumption of mammalian
meat led to a complete absence of symptoms.
PMID- 25113225
TI - Solvent induced rapid modulation of micro/nano structures of metal carboxylates
coordination polymers: mechanism and morphology dependent magnetism.
AB - Rational modulation of morphology is very important for functional coordination
polymers (CPs) micro/nanostructures, and new strategies are still desired to
achieve this challenging target. Herein, organic solvents have been established
as the capping agents for rapid modulating the growth of metal-carboxylates CPs
in organic solvent/water mixtures at ambient conditions. Co-3,5
pyridinedicarboxylate (pydc) CPs was studied here as the example. During the
reaction, the organic solvents exhibited three types of modulation effect:
anisotropic growth, anisotropic growth/formation of new crystalline phase and the
formation of new crystalline phase solely, which was due to the variation of
their binding ability with metal cations. The following study revealed that the
binding ability was critically affected by their functional groups and molecular
size. Moreover, their modulation effect could be finely tuned by changing volume
ratios of solvent mixtures. Furthermore, they could be applied for modulating
other metal-carboxylates CPs: Co-1,3,5-benzenetricarboxylic (BTC), Zn-pydc and Eu
pydc etc. Additionally, the as-prepared Co-pydc CPs showed a fascinating
morphology-dependent antiferromagnetic behavior.
PMID- 25113226
TI - Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI,
HOVON/SAKK, SWOG and MD Anderson Cancer Center.
AB - Therapeutic resistance remains the principal problem in acute myeloid leukemia
(AML). We used area under receiver-operating characteristic curves (AUCs) to
quantify our ability to predict therapeutic resistance in individual patients,
where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using
data from 4601 patients with newly diagnosed AML given induction therapy with 3+7
or more intense standard regimens in UK Medical Research Council/National Cancer
Research Institute, Dutch-Belgian Cooperative Trial Group for
Hematology/Oncology/Swiss Group for Clinical Cancer Research, US cooperative
group SWOG and MD Anderson Cancer Center studies. Age, performance status, white
blood cell count, secondary disease, cytogenetic risk and FLT3-ITD/NPM1 mutation
status were each independently associated with failure to achieve complete
remission despite no early death ('primary refractoriness'). However, the AUC of
a bootstrap-corrected multivariable model predicting this outcome was only 0.78,
indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information
only slightly decreased the AUC (0.76). Prediction of resistance, defined as
primary refractoriness or short relapse-free survival, was even more difficult.
Our limited ability to forecast resistance based on routinely available
pretreatment covariates provides a rationale for continued randomization between
standard and new therapies and supports further examination of genetic and
posttreatment data to optimize resistance prediction in AML.
PMID- 25113228
TI - Olive mill wastewater treatment using a simple zeolite-based low-cost method.
AB - Olive mill wastewater (OMW), a liquid by-product of the olive oil industry,
represents a severe environmental problem owing to its high pollution load. In
this study, successive columns containing different types of natural materials
were investigated for their OMW treatment efficiency. Passing OMW through three
columns of gravel, fine sand, and a mixture of acidified cotton and zeolite
(weight:weight ratio of cotton:clinoptilolite of 2:1), followed by treatment with
activated charcoal (AC) and lime, was the best treatment in terms of the quality
of water obtained. This treatment decreased concentrations of [Formula: see text]
, B, K, P, and total fat in OMW by mean percentages of 78.0, 92.4, 66.6, 48.3,
and 93.3%, respectively. Furthermore, it decreased OMW turbidity and electric
conductivity (EC) by 96.8 and 48.4%, respectively. Most contaminants were removed
from the OMW in the cotton/clinoptilolite column owing to the high sorption
affinity of clinoptilolite on its active sites. The AC was efficient for organic
particle removal; meanwhile, lime was used to raise the pH of the treated OMW
(TOMW) from 2.9 to 5.1. This simple method enables us to obtain environmentally
friendly TOMW that can be safely used for irrigation.
PMID- 25113227
TI - The ill surgeon: a review of common work-related health problems amongst UK
surgeons.
AB - INTRODUCTION: Health-care workers are subjected to various occupational hazards
within the National Health Service (NHS). Surgeons are not excluded from this
group due to the nature of work carried out on a daily basis. As a result, we set
out to investigate the common work-related health issues a surgeon practising in
the UK may encounter. METHOD: A literature search conducted on PubMed, EMBASE,
MEDLINE(r) and Health Management Information Consortium (HMIC) revealed 66
literature papers between the years 1990 and 2013. Thirty-seven were excluded
from our review process for various reasons. RESULTS: Surgeons in the UK are
likely to be susceptible to stress, sharp injuries, burnout and psychiatric
morbidities, substance abuse and musculoskeletal pain. Noise-induced hearing loss
has been reported amongst orthopaedic surgeons due to the use of electric and air
powered drills and saws. No reports of skin-related illness, respiratory illness,
nosocomial infections or malignancies were found within the published UK
literature of our targeted group although they have been noted in other
specialties. CONCLUSION: These occupational hazards pose a huge risk to the NHS
and the personal well-being of its surgeons. As such, the importance of early
awareness and education alongside prompt intervention is duly emphasized.
PMID- 25113229
TI - Revisiting the relationship between environmental and financial performance in
Chinese industry.
AB - The debate on the relationship between corporate or industrial environmental
performance (EP) and financial performance (FP) has yet to be resolved, and
studies need to examine the possible moderating effects on the EP-FP link. We
argue that industrial EP has a positive effect on FP and that industrial
munificence and resource slack can moderate the EP-FP link. Using a dataset from
Chinese industrial firms, we examine the direct effect of industrial EP on FP and
the indirect effects of industrial munificence and resource slack on the EP-FP
link. Our results show that improving corporate or industrial-level EP
significantly influences FP and that slack resources play a significant role on
the EP-FP link. However, we found no significant moderating effect of industrial
munificence on the link.
PMID- 25113230
TI - The relationship between corporate environmental performance and environmental
disclosure: an empirical study in China.
AB - Based on a content analysis of 533 Chinese listed companies, this study examines
how corporate environmental performance affects not only the level of detail of a
company's environmental disclosures, but also what information is disclosed. The
results show that (1) both poor and good performers have more disclosure than the
median (i.e., "mixed") performers, which provides empirical evidence to support a
nonlinear relationship between corporate environmental performance and
environmental disclosure; (2) poor performers disclose more soft information on
environmental performance than good performers, and good performers disclose more
solid information; and (3) although poor performers increase disclosure after
being exposed as environmental violators, they avoid disclosing negative
environmental information, such as the violation and the associated penalties.
This study provides additional evidence for a nonlinear relationship between
environmental performance and disclosure in emerging markets, and suggests
environmental disclosure may not be a valid signal to differentiate good
performers from poor performers in contemporary China.
PMID- 25113232
TI - Fast and accurate pressure-drop prediction in straightened atherosclerotic
coronary arteries.
AB - Atherosclerotic disease progression in coronary arteries is influenced by wall
shear stress. To compute patient-specific wall shear stress, computational fluid
dynamics (CFD) is required. In this study we propose a method for computing the
pressure-drop in regions proximal and distal to a plaque, which can serve as a
boundary condition in CFD. As a first step towards exploring the proposed method
we investigated ten straightened coronary arteries. First, the flow fields were
calculated with CFD and velocity profiles were fitted on the results. Second, the
Navier-Stokes equation was simplified and solved with the found velocity profiles
to obtain a pressure-drop estimate (Deltap (1)). Next, Deltap (1) was compared to
the pressure-drop from CFD (Deltap CFD) as a validation step. Finally, the
velocity profiles, and thus the pressure-drop were predicted based on geometry
and flow, resulting in Deltap geom. We found that Deltap (1) adequately estimated
Deltap CFD with velocity profiles that have one free parameter beta. This beta
was successfully related to geometry and flow, resulting in an excellent
agreement between Deltap CFD and Deltap geom: 3.9 +/- 4.9% difference at Re =
150. We showed that this method can quickly and accurately predict pressure-drop
on the basis of geometry and flow in straightened coronary arteries that are
mildly diseased.
PMID- 25113231
TI - A low computational cost algorithm for REM sleep detection using single channel
EEG.
AB - The push towards low-power and wearable sleep systems requires using minimum
number of recording channels to enhance battery life, keep processing load small
and be more comfortable for the user. Since most sleep stages can be identified
using EEG traces, enormous power savings could be achieved by using a single
channel of EEG. However, detection of REM sleep from one channel EEG is
challenging due to its electroencephalographic similarities with N1 and Wake
stages. In this paper we investigate a novel feature in sleep EEG that
demonstrates high discriminatory ability for detecting REM phases. We then use
this feature, that is based on spectral edge frequency (SEF) in the 8-16 Hz
frequency band, together with the absolute power and the relative power of the
signal, to develop a simple REM detection algorithm. We evaluate the performance
of this proposed algorithm with overnight single channel EEG recordings of 5
training and 15 independent test subjects. Our algorithm achieved sensitivity of
83%, specificity of 89% and selectivity of 61% on a test database consisting of
2221 REM epochs. It also achieved sensitivity and selectivity of 81 and 75% on
PhysioNet Sleep-EDF database consisting of 8 subjects. These results demonstrate
that SEF can be a useful feature for automatic detection of REM stages of sleep
from a single channel EEG.
PMID- 25113233
TI - 'More than skin-deep': biological essentialism in response to a distinctiveness
threat in a stigmatized fan community.
AB - We investigated how group distinctiveness threats affect essentialist beliefs
about group membership in a stigmatized fan community. An experiment conducted on
817 members of the fan community revealed that highly identified fans who
perceived significant stigmatization were the most likely to endorse essentialist
beliefs about group membership when exposed to a distinctiveness threat via
comparison to a highly similar (vs. dissimilar) outgroup. These results bridge
essentialism research and research on distinctiveness threat by demonstrating the
mutability of group essentialism beliefs as a defensive response to
distinctiveness threats. Implications for future research are discussed.
PMID- 25113235
TI - An integrative review of promoting trust in the patient-primary care provider
relationship.
AB - AIM: An integrative review of empirical studies on factors promoting trust in the
patient-primary care provider relationship. BACKGROUND: Trust is essential to the
patient-provider relationship. Patients with high trust in their healthcare
providers have been found to have improved outcomes, including improved chronic
disease management, increased use of preventative services and satisfaction with
care. Breaches of trust in the healthcare system threaten trust. Exploring
factors that promote trust in the patient-provider relationship is warranted.
DESIGN: Integrative literature review. DATA SOURCES: Electronic databases
searched included CINAHL, MEDLINE and PsycARTICLES, using combinations of the key
term 'trust' with: concept, practitioner, provider, physician, developing,
creating, engendering, promoting and establishing. The results were limited to
original publications in English, published between 1998-2013. REVIEW METHODS: A
review of the literature was conducted by two independent reviewers based on the
criteria established by Cooper; Whittemore and Knafl; and Polit and Beck.
Methodological assessment tools were used to organize, evaluate the quality of
and synthesize the data. RESULTS: A new conceptual definition of promoting trust
is proposed that includes three core qualities: interpersonal and technical
competence, moral comportment and vigilance. Gaps in the literature still exist
related to rural, young adult, older adult and well patient populations.
CONCLUSION: The core qualities could serve as target areas for the development of
interventions aimed at modifying provider behaviours so that trust can be
established, maintained or improved. Future prospective longitudinal research
studies are needed that enhance understanding of trust with multiple primary care
provider types.
PMID- 25113234
TI - Determinants of overweight and obesity among Bangladeshi diabetic women of
reproductive age.
AB - BACKGROUND: Several reproductive disorders with overweight and obesity are now
known to be associated with insulin resistance. The study was aimed to assess the
proportion and determinants of overweight and obesity among diabetic women of
reproductive age. METHODS: This cross-sectional analytic study was conducted
among 888 diabetic women of reproductive age attending the out-patient department
(OPD) of the central hospital of the Diabetic Association. Body Mass Index (BMI)
was used to assess the general obesity. Waist Circumference (WC), Waist-Hip Ratio
(WHR) and Waist-Height Ratio (WHtR) were used to assess central obesity. RESULTS:
The overall prevalence of overweight was 22% (95% CI 19-24) and that of obesity
was 48% (95% CI 45-51). Prevalence of central obesity by waist circumference was
77%, by waist-hip ratio was 99.9% and by waist-height ratio was 89%. Overweight
and obesity were higher in the age group of 45-49 years (49%) and 35-44 years
(24%) respectively. On Pearson's correlation analysis, BMI and WC were
significantly correlated with age (r = 0.135, p = 0.001; r = 0.162, p = 0.001)
and income (r = 0.151, p = 0.001; r = 0.087, p = 0.009) respectively. WHR was
also correlated with income (r = 0.094, p = 0.005). Moreover, WHtR was
significantly correlated with age (r = 0.139, p = 0.001), income (r = 0.069, p =
0.04) and duration of diabetes (r = 0.073, p = 0.03).On binary logistic
regression analysis, BMI was significantly associated with age, income and
management of diabetes by Oral Hypoglycemic Agent (OHA) (p < 0.05). WC was
significantly associated with age, income and management of diabetes by OHA and
insulin (p < 0.05). Where, WHR was significantly associated only with duration of
diabetes (p < 0.05). WHtR was significantly associated with age (p < 0.05),
management of diabetes by OHA (p < 0.05) and insulin (p < 0.05) in this analysis.
CONCLUSIONS: A high prevalence of both overweight and obesity exists in diabetic
women of reproductive age in Bangladesh and it seems to be associated with
increasing age, income, duration of diabetes, and use of oral hypoglycemic
agents.
PMID- 25113236
TI - Migration protocol to estimate metal exposure from mouthing copper and tin alloy
objects.
AB - BACKGROUND: Low blood lead levels previously thought to pose no health risks may
have an adverse impact on the cognitive development of children. This concern has
given rise to new regulatory restrictions upon lead metal containing products
intended for child use. However few reliable experimental testing methods to
estimate exposure levels from these materials are available. METHODS: The present
work describes a migration test using a mimetic saliva fluid to estimate the
chronic exposure of children to metals such as lead while mouthing metallic
objects. The surrogate saliva medium was composed of: 150 mM NaCl, 0.16% porcine
Mucin and 5 mM buffer MOPS, adjusted to pH 7.2. Alloys samples, in the form of
polished metallic disc of known surface area, were subjected to an eight hours
test. RESULTS: Two whitemetal alloys Sn/Pb/Sb/Cu and three brass alloys Cu/Zn/Pb
were tested using the saliva migration protocol. In the case of the whitemetal
alloys, first order release kinetics resulting in the release of 0.03 and 0.51
MUg lead/cm2 after 8 hours of tests were observed, for lead contents of 0.05
0.07% and 5.5%, respectively. Brasses exhibited linear incremental release rates
of 0.043, 0.175 and 0.243 MUg lead/cm2h for lead contents of 0.1-0.2%, 1.7-2.2%
and 3.1-3.5%, respectively. The linear regression analysis of lead release rates
relative to Pb content in brasses yielded a slope of 0.08 MUg lead/cm2h%Pb (r2 =
0.92). Lead release rates were used to estimate the mean daily mouthing exposure
of a child to lead, according to age-specific estimates of mouthing time
behavior. Calculated daily intakes were used as oral inputs for the IEUBK
toxicokinetic model, predicting only marginal changes in blood lead levels (0.2
MUg lead/dL or less) for children aged 0.5 to 1 years old exposed to either class
of alloy. CONCLUSIONS: The results of this study as a whole support the use of
migration data of metal ions, rather than total metal content, to estimate health
risk from exposure to metals and metal alloys substances in children.
PMID- 25113237
TI - Combination of classical test theory (CTT) and item response theory (IRT)
analysis to study the psychometric properties of the French version of the
Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF).
AB - OBJECTIVE: The study aimed to examine the construct validity and reliability of
the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q
SF) according to both classical test and item response theories. METHOD: The
psychometric properties of the French version of this instrument were
investigated in a cross-sectional, multicenter study. A total of 124 outpatients
with a substance dependence diagnosis participated in the study. Psychometric
evaluation included descriptive analysis, internal consistency, test-retest
reliability, and validity. The dimensionality of the instrument was explored
using a combination of the classical test, confirmatory factor analysis (CFA),
and an item response theory analysis, the Person Separation Index (PSI), in a
complementary manner. RESULTS: The results of the Q-LES-Q-SF revealed that the
questionnaire was easy to administer and the acceptability was good. The internal
consistency and the test-retest reliability were 0.9 and 0.88, respectively. All
items were significantly correlated with the total score and the SF-12 used in
the study. The CFA with one factor model was good, and for the unidimensional
construct, the PSI was found to be 0.902. CONCLUSION: The French version of the Q
LES-Q-SF yielded valid and reliable clinical assessments of the quality of life
for future research and clinical practice involving French substance abusers. In
response to recent questioning regarding the unidimensionality or
bidimensionality of the instrument and according to the underlying theoretical
unidimensional construct used for its development, this study suggests the Q-LES
Q-SF as a one-dimension questionnaire in French QoL studies.
PMID- 25113239
TI - Chaotic oscillation and random-number generation based on nanoscale optical
energy transfer.
AB - By using nanoscale energy-transfer dynamics and density matrix formalism, we
demonstrate theoretically and numerically that chaotic oscillation and random
number generation occur in a nanoscale system. The physical system consists of a
pair of quantum dots (QDs), with one QD smaller than the other, between which
energy transfers via optical near-field interactions. When the system is pumped
by continuous-wave radiation and incorporates a timing delay between two energy
transfers within the system, it emits optical pulses. We refer to such QD pairs
as nano-optical pulsers (NOPs). Irradiating an NOP with external periodic optical
pulses causes the oscillating frequency of the NOP to synchronize with the
external stimulus. We find that chaotic oscillation occurs in the NOP population
when they are connected by an external time delay. Moreover, by evaluating the
time-domain signals by statistical-test suites, we confirm that the signals are
sufficiently random to qualify the system as a random-number generator (RNG).
This study reveals that even relatively simple nanodevices that interact locally
with each other through optical energy transfer at scales far below the
wavelength of irradiating light can exhibit complex oscillatory dynamics. These
findings are significant for applications such as ultrasmall RNGs.
PMID- 25113240
TI - A mini me?: exploring early childhood diet with stable isotope ratio analysis
using primary teeth dentin.
AB - OBJECTIVES: Reconstruct childhood diet using teeth collected in Edmonton in a
collaborative effort between the Departments of Dentistry and Anthropology at the
University of Alberta. METHODS: Deciduous teeth needing extraction were collected
from 33 children for stable isotope ratio analysis of diet. Tooth dentin was
microsampled in three locations using a newly developed technique to reconstruct
the changing pattern of participants' diet through early childhood including
breastfeeding practices. RESULTS: The microsampling method can reconstruct diet
with tiny samples (0.3 mg). The results reconstruct fetal isotope ratios, which
showed significant variation. delta(15)N values indicate some children were being
breastfed (7/17), while others were likely bottle fed (10/17). Surprisingly, the
early childhood results do not show the range of diets expected in adults based
on known eating habits. Toddler diets form a tight cluster implying diets of
similar isotopic composition in almost all of the households despite potential
cultural and class distinctions (delta(15)N values 11-11.50/00, delta(13)C values
around -180/00). The delta(13)C values show a strong C3 dependence for most
children, a two outliers show C4 (-120/00) dependence indicating a possible corn
based diet. CONCLUSIONS: Microsampling can potentially track each child's diet
through early childhood. For this group of children, both breastfeeding and
bottle feeding was practiced. However, the percent of breastfed infants was less
than reported Canadian rates. Surprisingly, the choice to breastfeed or to bottle
feed was not linked to the choice of toddler diet. All toddler diets were
narrower in scope than adult diets.
PMID- 25113238
TI - Predictors of changes in physical, psychosocial, sexual quality of life, and
comfort with food after obesity surgery: a 12-month follow-up study.
AB - PURPOSE: Although obesity surgery provides significant postoperative improvement
in quality of life (QoL), it is still unclear which factors might predict
improvement in QoL after surgery. We aimed to determine which factors might
predict changes in physical, psychosocial, sexual QoL, and comfort with food 12
months after surgery, by putting to the test a QoL model based on Wilson and
Cleary's model. METHODS: We included 126 obese patients (48.4% had gastric
banding, 34.1% had sleeve gastrectomy, and 17.5% had gastric bypass). At
baseline, we assessed QoL (Quality of Life, Obesity and Dietetics rating scale),
BMI, depression (Beck Depression Inventory), and binge eating (Bulimic
Investigatory Test, Edinburgh). At 12 months, we assessed QoL and BMI. To
determine the predictors for changes in each QoL dimension after surgery, we used
linear mixed models adjusted for preoperative age, BMI, time, type of surgery,
preoperative binge eating severity, and preoperative depression severity.
RESULTS: After 12 months, we found significant improvement in physical,
psychosocial, sexual QoL, but not in comfort with food. Increased weight loss was
associated with better improvement in physical and psychosocial QoL. Higher
preoperative depression severity predicted poorer improvement in physical,
psychosocial, and sexual QoL. Higher preoperative binge eating severity predicted
poorer improvement in psychosocial, sexual QoL, and comfort with food.
CONCLUSIONS: In addition to weight loss, preoperative levels of binge eating and
depression should be considered as important predictors for QoL changes after
bariatric surgery. Screening and treatment for preoperative depression and binge
eating might improve QoL after bariatric surgery.
PMID- 25113241
TI - Effect of clodronate treatment on risk of fracture: a systematic review and meta
analysis.
AB - A systematic review and a meta-analysis of data of literature were performed to
evaluate the efficacy of clodronate in the reduction of risk of fractures in
patients with osteoporosis or tumour diseases. A systematic review was conducted
to identify original articles, reviews, and any other literature report suitable
for the purposes of the meta-analysis, limited to prospective randomized trials
that included a placebo or an untreated control arm. The search has identified 18
trials, 13 of which in patients with cancer diseases (breast cancer and multiple
myeloma were prevalent), 4 in patients with osteoporosis/low BMD, and 1 in
elderly women living in community. A placebo control arm was used in 13 trials.
Treatment and follow-up duration ranged from 3 months to 5 years. The meta
analysis showed that treatment with clodronate was associated with a reduction of
the probability of new fractures compared with controls (OR = 0.572, 95% CI 0.465
0.704 for new vertebral fractures; OR = 0.668, 95% CI 0.494-0.905 for new non
vertebral fractures; and OR = 0.744, 95% CI 0.635-0.873 for new overall fractures
in those articles where vertebral and non-vertebral new fractures were not
considered separately). Similar findings were observed in the separate analysis
in patients with cancer forms or osteoporosis. The results of the meta-analysis
have demonstrated that clodronate is effective in reducing the risk of vertebral,
non-vertebral, and overall fractures in patients with skeletal fragility.
PMID- 25113242
TI - The relevance of rhythmical alternation in language processing: an ERP study on
English compounds.
AB - This study investigates the influence of rhythmic expectancies on language
processing. It is assumed that language rhythm involves an alternation of strong
and weak beats within a linguistic domain. Hence, in some contexts rhythmically
induced stress shifts occur in order to comply with the Rhythm Rule. In English,
this rule operates to prevent clashes of stressed adjacent syllables or lapses of
adjacent unstressed syllables. While previous studies investigated effects on
speech production and perception, this study focuses on brain responses to
structures either obeying or deviating from this rule. Event-related potentials
show that rhythmic regularity is relevant for language processing: rhythmic
deviations evoked different ERP components reflecting the deviance from rhythmic
expectancies. An N400 effect found for shifted items reflects higher costs in
lexical processing due to stress deviation. The overall results disentangle
lexical and rhythmical influences on language processing and complement the
findings of previous studies on rhythmical processing.
PMID- 25113243
TI - The Sphagnum microbiome supports bog ecosystem functioning under extreme
conditions.
AB - Sphagnum-dominated bogs represent a unique yet widely distributed type of
terrestrial ecosystem and strongly contribute to global biosphere functioning.
Sphagnum is colonized by highly diverse microbial communities, but less is known
about their function. We identified a high functional diversity within the
Sphagnum microbiome applying an Illumina-based metagenomic approach followed by
de novo assembly and MG-RAST annotation. An interenvironmental comparison
revealed that the Sphagnum microbiome harbours specific genetic features that
distinguish it significantly from microbiomes of higher plants and peat soils.
The differential traits especially support ecosystem functioning by a symbiotic
lifestyle under poikilohydric and ombrotrophic conditions. To realise a
plasticity-stability balance, we found abundant subsystems responsible to cope
with oxidative and drought stresses, to exchange (mobile) genetic elements, and
genes that encode for resistance to detrimental environmental factors, repair and
self-controlling mechanisms. Multiple microbe-microbe and plant-microbe
interactions were also found to play a crucial role as indicated by diverse genes
necessary for biofilm formation, interaction via quorum sensing and nutrient
exchange. A high proportion of genes involved in nitrogen cycle and recycling of
organic material supported the role of bacteria for nutrient supply. 16S rDNA
analysis indicated a higher structural diversity than that which had been
previously detected using PCR-dependent techniques. Altogether, the diverse
Sphagnum microbiome has the ability to support the life of the host plant and the
entire ecosystem under changing environmental conditions. Beyond this, the moss
microbiome presents a promising bio-resource for environmental biotechnology -
with respect to novel enzymes or stress-protecting bacteria.
PMID- 25113244
TI - The relationship between glucocorticoid receptor polymorphisms, stressful life
events, social support, and post-traumatic stress disorder.
AB - BACKGROUND: It is debatable whether or not glucocorticoid receptor (GR)
polymorphisms moderate susceptibility to PTSD. Our objective was to examine the
effects of stressful life events, social support, GR genotypes, and gene
environment interactions on the etiology of PTSD. METHODS: Three tag single
nucleotide polymorphisms, trauma events, stressful life events, and social
support were assessed in 460 patients with PTSD and 1158 control subjects from a
Chinese Han population. Gene-environment interactions were analyzed by
generalized multifactor dimensionality reduction (GMDR). RESULTS: Variation in GR
at rs41423247 and rs258747, stressful life events, social support, and the number
of traumatic events were each separately associated with the risk for PTSD. A
gene-environment interaction among the polymorphisms, rs41423247 and rs258747,
the number of traumatic events, stressful life events, and social support
resulted in an increased risk for PTSD. High-risk individuals (a large number of
traumatic events, G allele of rs258747 and rs41423247, high level stressful life
events, and low social support) had a 3.26-fold increased risk of developing PTSD
compared to low-risk individuals. The association was statistically significant
in the sub-groups with and without childhood trauma. CONCLUSIONS: Our data
support the notion that stressful life events, the number of trauma events, and
social support may play a contributing role in the risk for PTSD by interacting
with GR gene polymorphisms.
PMID- 25113245
TI - Incidence and risk factors for AIDS-related mortality in HIV patients in China: a
cross-sectional study.
AB - BACKGROUND: To estimate the incidence and risk factors for mortality in HIV-1
infected patients in China. METHODS: Information on AIDS-related deaths was
collected from the Chinese Center for Disease Control and Prevention's Disease
Surveillance Information Reporting System and AIDS Prevention and Control
Information System. RESULTS: A total of 379,348 HIV cases were recorded in the
databases from 2006. Among those, 138,288 patients were reported as having
developed AIDS and 72,616 (19%) died of AIDS after data was extracted from the
databases in January 2011. Mortality was higher among those patients aged 50
years old or older (AOR: 3.41, CI: 1.47-7.91) who had been infected by
intravenous drug use (AOR: 1.65, CI: 1.28-2.14) or blood transfusion/donation
(AOR: 2.18: 1.18-3.99). Compared to patients who had not initiated highly active
antiretroviral therapy (HAART), those who had initiated HAART were more likely to
have a long interval of time between infection confirmation and AIDS-related
death. CONCLUSIONS: The effective reduction of AIDS mortality could be improved
through timely treatment.
PMID- 25113246
TI - Intravitreal bevacizumab versus posterior subtenon triamcinolone in diffuse
diabetic macular edema.
AB - The aim of the study was to compare intravitreal bevacizumab (IVB) and posterior
subtenon triamcinolone (PST) as an adjunct to laser treatment in diffuse diabetic
macular edema (Diffuse DME). Prospective-randomized control trial of 30 eyes of
30 diabetic patients having Diffuse DME with maximum retinal thickness (MRT) was
more than or equal to 350 um. The subjects were randomly allocated into two
groups. Group A (12 eyes) received IVB and group B received PST (18 patients)
before laser treatment. Grid laser treatment was done when the MRT decreased to
less than 350 um. OCT thickness-guided repeat injections were given if required.
The patients had minimum follow-up of 6 months. At 6-month follow-up, the two
groups were compared for (1) Maximum change in visual acuity letter score using
logMAR chart (2) Reduction in MRT on OCT. The mean logMAR visual acuity at
baseline was 0.63 +/- 0.45 (0-1.6) in group A and was 0.76 +/- 0.38 (0.2-1.3) in
group B. The mean logMAR visual acuity at 6 month in group A was 0.34 +/- 0.21 (0
0.6) and in group B was 0.64 +/- 0.37 (0.3-1.3). The mean visual acuity at last
follow-up was significantly better in group A than group B (p = 0.02). The mean
change in MRT in Group A and Group B was 177.8 +/- 85.64 and 156.07 +/- 102.86,
respectively, which was significantly better than the baseline in both the groups
and was comparable in both groups. The study provides evidence to support the use
of IVB over PST in diffuse diabetic macular edema.
PMID- 25113247
TI - Au@Pt nanoparticle encapsulated target-responsive hydrogel with volumetric bar
chart chip readout for quantitative point-of-care testing.
AB - Point-of-care testing (POCT) with the advantages of speed, simplicity,
portability, and low cost is critical for the measurement of analytes in a
variety of environments where access to laboratory infrastructure is lacking.
While qualitative POCTs are widely available, quantitative POCTs present
significant challenges. Here we describe a novel method that integrates an Au
core/Pt shell nanoparticle (Au@PtNP) encapsulated target-responsive hydrogel with
a volumetric bar-chart chip (V-Chip) for quantitative POCT. Upon target
introduction, the hydrogel immediately dissolves and releases Au@PtNPs, which can
efficiently catalyze the decomposition of H2 O2 to generate a large volume of O2
to move of an ink bar in the V-Chip. The concentration of the target introduced
can be visually quantified by reading the traveling distance of the ink bar. This
method has the potential to be used for portable and quantitative detection of a
wide range of targets without any external instrument.
PMID- 25113248
TI - Focal adhesion kinase inhibitors in the treatment of metastatic cancer: a patent
review.
AB - INTRODUCTION: Focal adhesion kinase (FAK) plays a prominent role in integrin
signaling. FAK activation increases phosphorylation of Tyr397 and other sites of
the protein. FAK-dependent activation of signaling pathways implicated in
controlling essential cellular functions including growth, proliferation,
survival and migration. FERM (F for the 4.1 protein, ezrin, radixin and moesin)
domain-enhanced p53 degradation plays a critical role in proliferation and
survival. FAK, overexpressed in metastatic tumors, has emerged as an important
therapeutic target for the development of selective inhibitors. FAK inhibitors
achieved tumor growth inhibition and induced apoptosis. Strategies targeting FAK
inhibition using novel compounds have created an exciting opportunity for
anticancer therapy. AREAS COVERED: This review summarizes the current research
with available data from early phase clinical trials and discusses the available
small-molecule inhibitors of FAK from patents. The importance of inhibiting FAK
activity in cancer patients is discussed. EXPERT OPINION: Emerging data from
clinical trials with orally available small-molecule inhibitors of FAK are
promising. Although this approach is appropriate as a targeted therapeutic
approach against several metastatic cancer types, several compounds in research
are yet to prove their preclinical efficacy. This report lays special emphasis on
the available patent data of FAK inhibitors for such targeted molecular
therapies. This review summarizes current knowledge about FAK inhibition in
cancer therapy.
PMID- 25113249
TI - The prognosis significance of TGF-beta1 and ER protein in cervical adenocarcinoma
patients with stage Ib~IIa.
AB - The incidence of stage Ib~IIa of cervical adenocarcinoma accounts about 60 to 70%
of all patients. This study aims to investigate the prognostic significance of
protein estrogen receptor alpha (ERalpha) and transforming growth factor beta 1
(TGF-beta1) level in different glandular epithelia of the cervix. In this study,
immunohistochemistry was used to detect ERalpha and TGF-beta1 in carcinomas and
incisal margins of 66 cases with cervical adenocarcinoma, 20 cases with normal
cervix, and 20 cases with chronic cervicitis. Uni- and multivariate analysis was
applied to evaluate the prognostic significance of TGF-beta1 and ERalpha in
carcinomas. The results indicated that the positive expression of TGF-beta1 in
carcinomas was 71.21%, significantly higher compared to that in the normal cervix
(35%) and chronic cervicitis (55%) (chi(2) = 8.901, P = 0.012). Similarly, the
positive expression of ERalpha in the carcinomas was 68.18%, significantly higher
compared to the normal cervix (35%) and chronic cervicitis (50%) (chi(2) = 7.693,
P = 0.021). Both TGF-beta1 and ERalpha in the carcinomas were associated with the
vaginal recurrence, infection of HPV, depth of infiltration, and lymphatic
metastasis (P < 0.05). The conjugation of TGF-beta1 and ERalpha was an
independent prognostic factor for cervical adenocarcinoma. Survival curve showed
that the positive TGF-beta1 and ERalpha indicated a short lifetime of patient
with cervical adenocarcinoma. In conclusion, the expression of TGF-beta1 and
ERalpha protein in the carcinomas had a significant prognostic value in a patient
of stage Ib~IIa in cervical adenocarcinoma.
PMID- 25113250
TI - Fucoxanthin induces apoptosis in human cervical cancer cell line HeLa via
PI3K/Akt pathway.
AB - Cervical cancer (CC) is a malignant neoplasm arising from cells originating in
the cervix uteri, among the top causes of death from cancer in women. In a gene
expression profiling study of metabolic response to treatment, PI3K/Akt signaling
pathway are associated with the development of CC. A common mechanism of Akt
activation seen in cancer types is alterations in the upstream regulators of Akt
such as phosphatidylinositol 3-kinase (PI3K), which is overexpressed in cervical
cancer tissues, and leads to phosphorylation of Akt. Both PI3K and Akt inhibitors
exist and may be therapeutically valuable. In the present study, we use MTT assay
and western blot for the high-throughput screening to select specific inhibitors
of PI3K/Akt signaling pathway, and then obtain fucoxanthin. Fucoxanthin is a
water-soluble dietary fiber, taken from the unique slimy component of alginic
cells. Various studies have pointed out that fucoxanthin is very effective for
the treatment of cancer. Our results have shown that fucoxanthin induced a
significant apoptosis of HeLa cells, compared with other candidates. After
treatment with fucoxanthin for 24 h, the level of phosphorylation was inhibited
in a dose-dependent manner, and the proteins of apoptotic markers were changed in
HeLa cells. And fucoxanthin could suppress tumor growth in vivo. In addition, the
mitochondrial signal transduction pathway maybe was involved in its mechanism and
NF-kappaB activation was decreased after treatment with fucoxanthin. Therefore,
fucoxanthin may be used as anti-cervical cancer drugs in the future.
PMID- 25113251
TI - Association between the XPD/ERCC2 Lys751Gln polymorphism and risk of cancer:
evidence from 224 case-control studies.
AB - Genetic variations in the xeroderma pigmentosum group D (XPD) gene may increase
cancer susceptibility by affecting the capacity for DNA repair. A lot of studies
have reported the association of XPD Lys751Gln polymorphism with risk of cancer,
but the results remained controversial. Hence, we performed a systematic review
and conducted a meta-analysis to explore association of the XPD Lys751Gln
polymorphism with risk of cancer (78,398 cases and 103,178 controls from 224
studies). Overall, a significantly increased cancer risk was found in all genetic
models (dominant model: odds ratio (OR) = 1.10, 95% confidence interval (CI) =
1.06-1.14; recessive model: OR = 1.10, 95% CI = 1.05-1.15; homozygous model: OR =
1.14, 95% CI = 1.08-1.21; heterozygous model: OR = 1.09, 95% CI = 1.05-1.12;
additive model: OR = 1.08, 95% CI= 1.05-1.11) when all eligible studies were
pooled into the meta-analysis. In further stratified and sensitivity analyses,
the elevated risk of cancer remained for subgroups of breast cancer, esophageal
cancer, hepatocellular cancer, leukemia, lung cancer, and melanoma. In summary,
this meta-analysis suggests the XPD Lys751Gln polymorphism is a genetic
susceptibility for some cancer types. Moreover, ethnicity, histological type of
cancer, and smokers seem to contribute to varying expressions of the Lys751Gln on
some cancer risk. In addition, our work also points out the importance of new
studies for Lys751Gln association in endometrial cancer and ovarian cancer, where
at least some of the covariates responsible for heterogeneity could be
controlled, to obtain a more conclusive understanding about the function of the
Lys751Gln polymorphism in cancer development.
PMID- 25113252
TI - COX-2 overexpression and -8473 T/C polymorphism in 3' UTR in non-small cell lung
cancer.
AB - A new class of compounds targeting cyclooxygenase 2 (COX-2) together with other
different clinically used therapeutic strategies has recently shown a promise for
the chemoprevention of several solid tumors including lung cancer. The aim was to
study the possible role of COX-2 -8473 T/C NP and its expression in the
pathogenesis of non-small cell lung cancer. One hundred ninety non-small cell
lung cancer (NSCLC) patients and 200 healthy age-, sex-, and smoking-matched
controls were used for polymorphic analysis, and 48 histopathologically confirmed
NSCLC patients were analyzed for COX-2 messenger RNA (mRNA) and protein
expression. Our results showed that the frequencies of variant genotypes 8473
CT/CC were significantly less common in the cases (30.0%) than in the controls
(36%), suggesting that the 8473 C variant allele is related with lower
susceptibility in NSCLC (OR = 0.79, 95% CI 0.54-1.4). However, the frequency of
COX-2 -8473 TC and CC genotypes were significantly associated with age in NSCLC
(P = 0.02). Quantitative real-time expression analysis showed a significant
increase in the COX-2 mRNA in tumor tissues as compared to their adjacent normal
tissues [delta cycle threshold (DeltaCT) = 9.25 +/- 4.67 vs 5.63 +/- 3.85, P =
0.0001]. Multivariate logistic regression analyses revealed that the COX-2
expression was associated significantly with age (P = 0.044). Also, an increasing
trend was observed in stages I and II and in female patients compared to stages
III and IV and male patients, respectively, but no statistical significance was
observed. However, COX-2 mRNA expression shown no association with the -8473 C
variant allele. Our findings indicate that the COX-2 T8473C polymorphism may
contribute to NSCLC cancer susceptibility in the Kashmiri population, while our
expression analysis revealed a significant increase of COX-2 in tumor tissues as
compared to their adjacent normal tissues, suggesting that it could become an
important therapeutic marker in NSCLC in the future.
PMID- 25113253
TI - Vascular marker expression during the development of various types of
gynaecological malignancy.
AB - Clinical diagnosis of gynaecological malignancies is usually successful in the
advanced stages of the tumour, and this has a major impact on the success of
therapy. Therefore, in the last few years, cancer research has tried to identify
and characterise new biochemical and molecular markers needed as predictive
indicators for the diagnosis of cancer. Our aim has been to search the molecular
changes in gene expression of death receptor 6, glycoprotein M6B (Gpm6B) and
genes associated with tumours of the female genital system. After isolation of
messenger RNA (mRNA), transcription of mRNA into the cDNA was performed. The
quantification of gene expression changes was detected using the reverse
transcription polymerase chain reaction (RT-PCR) method. Analysis at the protein
level was performed using the Western blot method. In both methods, we used actin
as a housekeeping gene for normalisation. Numerical quantification of changes in
expression and in the level of the specific proteins was evaluated using the Data
Syngene program. Significant changes in the levels of protein and mRNA expression
were detected, mainly in the death receptor 6 (Dr6) gene of patients suffering
from cancer of the corpus and cervix uteri and ovarian cancer, which also
corresponded with the level of protein Dr6. At the level of transcription, a
significant increase in the expression levels of mRNA for the Gpm6B gene was
detected, which led to an increase in corresponding protein in the peripheral
blood of patients with gynaecological tumours against the healthy control group.
This article could help to find an adequate marker for clinical application that
will enable more sensitive detection of the early stages of gynaecological
malignancies from the peripheral blood of patients.
PMID- 25113256
TI - Core outcomes for reporting women's health.
PMID- 25113255
TI - Comment on Zhuang YF et al.: impact of vascular endothelial growth factor
expression on overall survival in patients with osteosarcoma: a meta-analysis.
PMID- 25113254
TI - A functional and protein-protein interaction analysis of neuroepithelial cell
transforming gene 1 in hepatocellular carcinoma.
AB - In our previous study, we reported that the expression of neuroepithelial
transforming gene 1 (NET1) was increased in hepatocellular carcinoma (HCC)
tissues and suggested that NET1 may serve as a novel prognostic predictor and a
useful target for HCC therapy. The aim of this study was to determine the role of
NET1 in HCC by monitoring the proliferation, migration, invasion, and metastasis
of HCC cells in which NET1 has been stably knocked down. Additionally, to provide
targets for therapeutic intervention, we aimed to identify the protein which
interacts with NET1. NET1 knockdown significantly reduced the migration,
invasion, and metastasis of MHCC-97H cells by 44, 65, and 77%, respectively,
while cell proliferation was not significantly altered following NET1 knockdown.
During our efforts to find potential NET1 modulators through protein-protein
interactions, we identified merlin as a NET1-binding protein in a yeast two
hybrid screen. The interaction between NET1 and merlin was confirmed by co
immunoprecipitation. We found that the levels of NET1 protein decreased along
with the increase of merlin levels. Furthermore, we demonstrated that merlin
facilitates NET1 ubiquitination via the ubiquitin-proteasome pathway. Taken
together, this study suggests that NET1 plays an important role in HCC cell
migration, invasion, and metastasis, which are key aspects of HCC progression.
Furthermore, merlin may serve as a tumor suppressor for HCC by facilitating
ubiquitination of NET1.
PMID- 25113258
TI - Intraoperative powdered vancomycin use with paddle lead placement.
AB - OBJECTIVES: This is a prospective case-control study that was conducted to
determine if the addition of intraoperative powdered vancomycin placed directly
into the wounds at the time of closure might decrease the rate of acute
postoperative infection after the placement of spinal cord stimulator paddle
leads. MATERIALS AND METHODS: A retrospective analysis of the author's practice
from January 1, 2009 through July 31, 2012 (Table 1) showed that those patients
requiring a laminectomy instead of a laminotomy to insert a paddle lead had an
increased rate of acute postop infection. All patients receiving a thoracic
spinal cord stimulator paddle from January 1, 2013 through December 31, 2013 were
then followed prospectively. Those patients whose paddle leads could be inserted
with a laminotomy were treated in a standard fashion. Those patients who required
a laminectomy for insertion of the paddle lead received powdered vancomycin
placed directly into the wounds prior to closure. RESULTS: One hundred and nine
patients underwent implantation of a permanent spinal cord stimulator paddle lead
and battery between January 1 and December 31, 2013. Thirty-two of those patients
required a laminectomy for implantation of the paddle and received intraoperative
powdered vancomycin placed directly into both wounds at the time of closure. The
remaining 77 patients were treated in a standard fashion. There were no
infections in the laminectomy group and two infections in the laminotomy group.
CONCLUSION: This study indicates that intraoperative powdered vancomycin placed
directly into the wounds at the time of closure can produce similar infection
rates between the groups of patients requiring a laminectomy vs. a laminotomy for
implantation of a thoracic paddle lead. These findings need confirmation by a
randomized controlled design study.
PMID- 25113257
TI - Cystoprostatectomy versus prostatectomy alone for locally advanced or recurrent
pelvic cancer.
AB - BACKGROUND: There is minimal published data evaluating the oncological outcome of
rectal resection with prostatectomy alone versus rectal resection with
cystoprostatectomy in patients undergoing pelvic exenteration for locally
advanced or recurrent pelvic cancer. This study aims to evaluate the oncological
and functional outcomes of performing rectal resection with prostatectomy alone
compared with rectal resection with cystoprostatectomy in patients undergoing
pelvic exenteration. METHODS: Consecutive patients undergoing pelvic exenteration
for locally advanced or recurrent pelvic cancer between 1998 and 2012 were
identified from a prospectively maintained database. Patients undergoing rectal
resection with prostatectomy alone were compared with a control group who
underwent rectal resection with cystoprostatectomy and urostomy formation. The
primary outcome was overall survival. Secondary outcomes analysed in the
prostatectomy group included completeness of resection, continence and erectile
function. RESULTS: Eleven rectal resections with prostatectomy were compared with
20 rectal resections with cystoprostatectomy. R0 resection was achieved in 73 and
65% respectively. There was no difference in overall survival (P = 0.40). Urinary
continence was achieved in 36% of prostatectomy alone patients, while 27%
experienced mild incontinence. Erectile function was poor, with only one patient
able to maintain normal erections. CONCLUSION: In appropriately selected patients
with invasive pelvic tumours, rectal resection with prostatectomy alone provides
adequate oncological outcomes. The ability to achieve an R0 resection was not
compromised and overall survival is comparable with cystoprostatectomy. Urinary
function is reasonable in most patients, although sexual function is compromised
in almost all.
PMID- 25113259
TI - Clinical and radiologic evaluation of arthroscopic medial meniscus root tear
refixation: comparison of the modified Mason-Allen stitch and simple stitches.
AB - PURPOSE: This study compared the clinical and radiologic outcomes of arthroscopic
medial meniscus root refixation using the modified Mason-Allen stitch and simple
stitches. METHODS: The outcomes of 25 patients who underwent arthroscopic
meniscus root refixation using the modified Mason-Allen stitch (M group) between
June 2010 and January 2012 were compared with those of 25 matched control
patients (S group) who underwent meniscus root refixation using simple stitches
between March 2004 and August 2007. The Lysholm score, International Knee
Documentation Committee Subjective Knee Form score, joint space narrowing, and
Kellgren-Lawrence grade were assessed. Medial meniscal extrusion, progression of
cartilage degeneration, and healing status of the refixed medial meniscus root
were assessed on magnetic resonance images. RESULTS: No between-group difference
was found in age, sex, body mass index, or preoperative patient characteristics.
The mean follow-up times for the M and S groups were 24.1 and 25.9 months (P =
.248), respectively. The Lysholm, International Knee Documentation Committee
Subjective Knee Form, and Tegner activity scores improved significantly in both
groups. The repaired root tended to heal better in the M group than in the S
group (P = .065). Although the postoperative clinical outcomes did not differ
between the groups, postoperative medial meniscal extrusion decreased -0.6 +/-
0.9 mm in the M group and increased 1 +/- 0.6 mm in the S group on magnetic
resonance imaging (P < .001). The M group did not show significant progression in
the Kellgren-Lawrence grade and cartilage degeneration (P = .083 and P = .317,
respectively), whereas both measures increased significantly in the S group (P =
.008 and P < .001, respectively). CONCLUSIONS: Compared with simple stitches, the
modified Mason-Allen stitch improved the degree of meniscal extrusion, although
the 2 different suture techniques showed no difference in clinical outcomes at
short-term follow-up. LEVEL OF EVIDENCE: Level III, retrospective comparative
study.
PMID- 25113261
TI - Resistance to the antiproliferative effect induced by a short-chain ceramide is
associated with an increase of glucosylceramide synthase, P-glycoprotein, and
multidrug-resistance gene-1 in cervical cancer cells.
AB - PURPOSE: Ceramide is glycosylated to glucosylceramide or lactosylceramide, and
this glycosylation is a novel multidrug-resistance (MDR) mechanism. In this work,
a short-chain ceramide (C6), lactosylceramide (LacCer), and an inhibitor of
ceramide glycosylation (D-threo-1-phenyl-2-decanoylamino-3-1-propanol, PDMP) were
evaluated on the proliferation of cervical cancer cells. The participation of
glucosylceramide synthase (GCS), P-glycoprotein (P-gp), and multidrug-resistance
gene-1 (MDR-1) in the resistance to the antiproliferative effect induced by C6
was also evaluated. METHODS: Cell proliferation was determined by crystal violet
staining. GCS and MDR-1 mRNA expression was evaluated by real-time RT-PCR assay.
GCS and P-gp protein expressions, as well as Rhodamine 123 uptake, which is a
functional test for P-gp efflux activity, were determined by flow cytometry.
RESULTS: C6 inhibited proliferation of CaLo and CasKi cells with an IC50 of 2.5
MUM; however, 50% proliferation of ViBo cells was inhibited with 10 MUM. LacCer
increased the proliferation of all cells. When cells were treated with PDMP plus
C6, no additional effect on antiproliferation induced by C6 was observed in CaLo
and CasKi cells; however, proliferation diminished in comparison with C6 alone in
ViBo cells. C6 increased GCS and MDR-1 expression in all cells, as well as P-gp
expression in CasKi cells. CONCLUSIONS: Cells that have more capacity to
glycosylate ceramide and express a higher level of GCS, MDR-1, and P-gp, are more
resistant to the antiproliferative effect induced by C6.
PMID- 25113262
TI - Combined effects of the cyanobacterial toxin microcystin-LR and environmental
factors on life-history traits of indigenous cladoceran Moina macrocopa.
AB - Environmental factors are important in that they might interact with toxicants
and could affect the concentration-response relationship of the toxicants in the
water environment. Microcystins (MCs) produced by algal blooming are natural
toxins that exert severe impacts on aquatic organisms. Despite the possibility of
interaction effects between environmental factors and MCs, very few studies have
been carried out to date. In the present study, the authors evaluated the effect
of 3 environmental factors on chronic toxicity of MC-leucine-arginine (MC-LR; 0
ug/L, 0.8 ug/L, 4 ug/L, 20 ug/L, 100 ug/L, 500 ug/L) to the freshwater
invertebrate Moina macrocopa. Three environmental factors were determined to
reflect the reasonable worst conditions of the water body in South Korea: high
water temperature (25 degrees C), the highest concentration of nutrients
(ammonia-nitrogen [NH3 -N] = 3.8 mg/L; nitrate-nitrogen [NO3 -N] = 8.5 mg/L)
during the occurrence of algal bloom, and 2 pH conditions of 7.0 and 9.0, which
satisfy the test acceptance criteria for the Daphnia test. Among the various
environmental factors being tested, high water temperature and NO3 -N elevated
chronic toxicity of MC-LR, whereas NH3 -N reduced toxicity. Water pH did not
influence chronic toxicity of MC-LR to M. macrocopa. This observation suggests
that those environmental factors are responsible for changing the trend of MC-LR
toxicity.
PMID- 25113263
TI - Hydrogel doped with nanoparticles for local sustained release of siRNA in breast
cancer.
AB - Of all the much hyped and pricy cancer drugs, the benefits from the promising
siRNA small molecule drugs are limited. Lack of efficient delivery vehicles that
would release the drug locally, protect it from degradation, and ensure high
transfection efficiency, precludes it from fulfilling its full potential. This
work presents a novel platform for local and sustained delivery of siRNA with
high transfection efficiencies both in vitro and in vivo in a breast cancer mice
model. siRNA protection and high transfection efficiency are enabled by their
encapsulation in oligopeptide-terminated poly(beta-aminoester) (pBAE)
nanoparticles. Sustained delivery of the siRNA is achieved by the enhanced
stability of the nanoparticles when embedded in a hydrogel scaffold based on
polyamidoamine (PAMAM) dendrimer cross-linked with dextran aldehyde. The
combination of oligopeptide-terminated pBAE polymers and biodegradable hydrogels
shows improved transfection efficiency in vivo even when compared with the most
potent commercially available transfection reagents. These results highlight the
advantage of using composite materials for successful delivery of these highly
promising small molecules to combat cancer.
PMID- 25113260
TI - Impact of transpulmonary thermodilution-based cardiac contractility and
extravascular lung water measurements on clinical outcome of patients with
Takotsubo cardiomyopathy after subarachnoid hemorrhage: a retrospective
observational study.
AB - INTRODUCTION: Takotsubo cardiomyopathy (TCM) is a life-threatening systemic
consequence early after subarachnoid hemorrhage (SAH), but precise hemodynamics
and related outcome have not been studied. The purpose of this study was to
investigate the TCM-induced cardiac function by transpulmonary thermodilution and
its impact on clinical outcome of SAH. METHODS: We retrospectively analyzed 46
consecutive postoperative SAH patients who developed TCM. Patients were divided
into two groups of echocardiographic left ventricular ejection fraction (LVEF) <
40% (TCM with left ventricular (LV) dysfunction) and LVEF >=40% (TCM without LV
dysfunction). Cardiac function index (CFI) and extravascular lung water index
(ELWI) were monitored by transpulmonary thermodilution, in parallel with serial
measurements of echocardiographic parameters and blood biochemical markers.
RESULTS: Transpulmonary thermodilution-derived cardiac function index (CFI) was
significantly correlated with (LVEF) (r = 0.82, P < 0.0001). The CFI between day
0 to day 7 was significantly lower in patients with LV dysfunction (LVEF <40%)
than in patients with LVEF >=40% (P < 0.05). CFI had a better ability than
cardiac output to detect cardiac dysfunction (LVEF < 40%) (area under the curve:
0.85 +/- 0.02; P < 0.001). A CFI value of < 4.2 min-1 had a sensitivity of 82%
and specificity of 84% for detecting LVEF <40%. The CFI < 4.2 min-1 was
associated with delayed cerebral ischemia (DCI) (odds ratio (OR), 2.14; 95%
confidence interval (CI), 1.33-2.86; P = 0.004) and poor 3-month functional
outcome on modified Rankin Scale of 4-6 (OR, 1.87; 95% CI, 1.06-3.29; P = 0.02).
An extravascular lung water index (ELWI) > 14 mL/kg after day 4 increased the
risk of poor functional outcome at 3-month follow-up (OR, 2.10; 95% CI, 1.11
3.97; P = 0.04). CONCLUSIONS: Prolonged cardiac dysfunction and pulmonary edema
increased the risk of DCI and poor 3-month functional outcome in patients with
SAH suffering from TCM. Serial measurements of CFI and ELWI by transpulmonary
thermodilution may provide an easy bedside method of detecting early changes of
the cardiopulmonary function in directing proper post-SAH treatment.
PMID- 25113265
TI - Editor's Spotlight/Take 5: Small improvements in mechanical axis alignment
achieved with MRI versus CT-based patient-specific instruments in TKA: a
randomized clinical trial.
PMID- 25113267
TI - Letter to the editor: anconeus interposition arthroplasty: mid- to long-term
results.
PMID- 25113266
TI - Does patient sex affect the anatomic relationships between the sternoclavicular
joint and posterior vascular structures?
AB - BACKGROUND: Despite increased concern for injury during surgical reconstruction
of the sternoclavicular joint, to our knowledge there are few studies detailing
the vascular relationships adjacent to the joint. QUESTIONS/PURPOSES: We
investigated sex differences in the following relationships for sternoclavicular
joint reconstruction: (1) safe distance from the posterior surface of the medial
clavicle's medial and lateral segments to the major vessels, (2) length of the
first costal cartilage and safe distance from the first rib to the internal
mammary artery, (3) minimum distance medial to the sternoclavicular joint for
optimal hole placement, and (4) safe distance from the manubrium to the great
vessels. METHODS: Fifty normal postcontrast CT scans of the chest were reviewed.
Means, standard deviations, and 95% CI were calculated for each aforementioned
measurement. A t-test was used to determine if a sex difference exists (p<=0.05).
RESULTS: At the medial end of the clavicle, the safe distance from the medial
segment (first 10 mm) to the major vessels was greater in males than in females
(3.5 mm versus 2.4 mm, respectively; 95% CI, 3 mm-4 mm versus 1.7 mm-3 mm,
respectively; p=0.014). For the lateral segment (next 10 mm), the distance also
was safer in males than in females (3.3 mm versus 1.7 mm, respectively; 95% CI,
2.7 mm-4 mm versus 1.1 mm-2.3 mm, respectively; p<0.001). The mean length of the
first costal cartilage also was greater in males (35.8 mm versus 30.1 mm,
respectively; 95% CI, 33.8 mm-37.8 mm versus 28.5 mm-31.9 mm, respectively;
p<0.001); the distance from the first costochondral joint to the internal mammary
artery was safer in males than in females (19.1 mm versus 15.4 mm, respectively;
95% CI, 16.5 mm-21.8 mm versus 13 mm-17.9 mm, respectively; p=0.05). The minimum
distance to avoid inadvertent penetration of the sternoclavicular joint was
greater in males than in females (16 mm versus 12.3 mm, respectively; 95% CI,
14.6 mm-17.5 mm versus 11 mm-13.6 mm, respectively; p<0.001). The distance to
vessels after penetration of the manubrium was not different between males and
females (5.6 mm versus 3.9, respectively; 95% CI, 4.4 mm-6.8 mm versus 2.6 mm-5.2
mm, respectively; p=0.06). CONCLUSIONS: This study makes apparent the intimate
relationships between vessels and the musculoskeletal structures associated with
sternoclavicular reconstruction. Based on our findings, we recommend considering
the sex of the patient, using caution when drilling, and protecting essential
structures posterior to the joint.
PMID- 25113268
TI - What is the work environment of orthopaedic surgeons in China?
AB - BACKGROUND: Physicians in China face heavy demands from patients and the
government for services but deal with the threat of unpredictable legal and
physical conflicts with patients, some ending with the death of doctors. More
than 40 doctors and nurses have been killed by patients since 2001.
QUESTIONS/PURPOSES: We sought to evaluate (1) the demographics of orthopaedic
practice, (2) duty periods, (3) practice support, and (4) job satisfaction among
orthopaedic surgeons in China. METHODS: Questionnaires were posted online at
www.OrthoChina.org for download by orthopaedic surgeons in 2006 to 2007, and sent
to those attending meetings in 2013. In 2013, a total of 1350 surgeons were
invited and 456 participated in the survey at meetings. In 2007, during the
period of the survey, 9759 individuals were qualified orthopaedic surgeons, and
334 participated in the survey at www.OrthoChina.org . RESULTS: Ninety-one
percent of orthopaedic surgeons work in public and 9% in private hospitals.
Ninety-four percent work more than 8 hours per day 6 to 7 days a week. Twenty
five percent work more than 12 hours per day 6 to 7 days a week without extra
compensation. The majority of orthopaedic surgeons must work on national
statutory holidays. Almost none received contractually mandated income for
weekends and national holidays. Approximately 80% of participants reported an
attack of some kind, including physical or psychologic harm. With respect to job
satisfaction, 73% stated they would not choose to be a physician again and 86%
reported that they do not want their children to become a physician. CONCLUSIONS:
China's rapid economic growth and resulting demands for modern health care have
resulted in heavy pressure on orthopaedic surgeons, financially and personally.
Chinese orthopaedic surgeons are overworked, suffer lack of respect, and face the
possibility of serious personal harm. As a consequence, they are demoralized and
unsatisfied. Significant reforms are needed.
PMID- 25113269
TI - Muscle fibers are injured at the time of acute and chronic rotator cuff repair.
AB - BACKGROUND: Rotator cuff tears are a common source of shoulder pain and
disability. Even after surgical repair, some patients continue to have reduced
function and progression of fatty degeneration. Because patients with chronic
cuff tears often experience muscle shortening, it is possible that repairing the
tendon to its anatomic footprint induces a stretch-induced muscle injury that
could contribute to failures of the repair and perhaps ongoing pain.
QUESTIONS/PURPOSES: We hypothesized that, compared with acutely torn and repaired
muscles, the stretch that is required to repair a chronically torn cuff would
result in more muscle fiber damage. Specifically, we asked: (1) Is there muscle
fiber damage that occurs from repair of an acutely torn rotator cuff and does it
vary by location in the muscle; and (2) is the damage greater in the case of
repair of a chronic injury? METHODS: We used an open surgical approach to create
a full-thickness rotator cuff tear in rats, and measured changes in muscle mass,
length, and the number of fibers containing the membrane impermeable Evans Blue
Dye after acute (1 day) or chronic (28 days) cuff tear or repair in rats.
Differences between groups were tested using a one-way ANOVA followed by Tukey's
post hoc sorting. RESULTS: Chronic tears resulted in 24% to 35% decreases in mass
and a 20% decrease in length. The repair of acutely and chronically torn muscles
resulted in damage to 90% of fibers in the distal portion of the muscle. In the
proximal portion, no differences between the acutely torn and repaired groups and
controls were observed, whereas repairing the chronically torn group resulted in
injury to almost 70% of fibers. CONCLUSIONS: In a rat model, marked injury to
muscle fibers is induced when the tendons of torn rotator cuffs are repaired to
their anatomic footprint. CLINICAL RELEVANCE: In this animal model, we found that
repair of chronically torn cuff muscles results in extensive injury throughout
the muscle. Based on these findings, we posit that inducing a widespread injury
at the time of surgical repair of chronically torn rotator cuff muscles may
contribute to the problems of failed repairs or continued progression of fatty
degeneration that is observed in some patients that undergo rotator cuff repair.
Therapeutic interventions to protect muscle fiber membranes potentially could
enhance outcomes for patients undergoing rotator cuff repair. To evaluate this,
future studies that evaluate the use of membrane sealing compounds or drugs that
upregulate endogenous membrane-sealing proteins are warranted.
PMID- 25113270
TI - Total serum transforming growth factor-beta1 is elevated in the entire spectrum
of genetic aortic syndromes.
AB - BACKGROUND: Total serum transforming growth factor-beta 1 (tsTGF-beta1) is
increased in patients with Marfan syndrome (MFS), but it has not been assessed in
thoracic aortic aneurysm and dissection (TAAD), Loeys-Dietz syndrome (LDS), and
bicuspid aortic valve disease (BAVD). HYPOTHESIS: tsTGF-beta1 is increased in
genetic aortic syndromes including TAAD, LDS, MFS, and BAVD. METHODS: We measured
tsTGF-beta1 and performed sequencing of the genes FBN1, TGFBR1, and TGFBR2 in 317
consecutive patients with suspected or known genetic aortic syndrome (167 men,
150 women; mean age 43 +/- 14 years). TAAD was diagnosed in 20, LDS in 20, MFS in
128, and BAVD in 30 patients, and genetic aortic syndrome was excluded in 119
patients. RESULTS: Elevated tsTGF-beta1 levels were associated with causative
gene mutations (P = 0.008), genetic aortic syndrome (P = 0.009), and sporadic
occurrence of genetic aortic syndrome (P = 0.048), whereas only genetic aortic
syndrome qualified as an independent predictor of tsTGF-beta1 (P = 0.001). The
tsTGF-beta1 levels were elevated in FBN1 and NOTCH1 mutations vs patients without
mutations (both P = 0.004), and in NOTCH1 mutations vs ACTA2/MYH11 mutations (P =
0.015). Similarly, tsTGF-beta1 levels were elevated in MFS (P = 0.003) and in
BAVD (P = 0.006) vs patients without genetic aortic syndrome. In contrast to
specific clinical features of MFS, FBN1 in-frame mutations (P = 0.019) were
associated with increased tsTGF-beta1 levels. CONCLUSIONS: tsTGF-beta1 is
elevated in the entire spectrum of genetic aortic syndromes. However, gradual
differences in the increases of tsTGF-beta1 levels may mirror different degrees
of alteration of tsTGF-beta1 signaling in different genetic aortic syndromes.
PMID- 25113272
TI - If doctors can train part time, why not medical students?
PMID- 25113271
TI - E pluribus unum, no more: from one crystal, many conformations.
AB - Several distinct computational approaches have recently been implemented to
represent conformational heterogeneity from X-ray crystallography datasets that
are averaged in time and space. As these modeling methods mature, newly
discovered alternative conformations are being used to derive functional protein
mechanisms. Room temperature X-ray data collection is emerging as a key variable
for sampling functionally relevant conformations also observed in solution
studies. Although concerns about radiation damage are warranted with higher
temperature data collection, 'diffract and destroy' strategies on X-ray free
electron lasers may permit radiation damage-free data collection. X-ray
crystallography need not be confined to 'static unique snapshots'; these
experimental and computational advances are revealing how the many conformations
populated within a single crystal are used in biological mechanisms.
PMID- 25113273
TI - High density EEG-what do we have to lose?
PMID- 25113274
TI - Upper limb function is normal in patients with restless legs syndrome (Willis
Ekbom Disease).
AB - OBJECTIVE: Restless legs syndrome, now called Willis-Ekbom Disease (RLS/WED), is
a sensorimotor-related sleep disorder. Little is known of the effect of RLS/WED
on motor function. The current study investigated upper limb function in RLS/WED
patients. We hypothesised that RLS/WED patients exhibit subtle changes in tremor
amplitude but normal dexterity and movement speed and rhythmicity compared to
healthy controls. METHODS: RLS/WED patients (n=17, 59 +/- 7 years) with moderate
disease and healthy controls (n=17, 58 +/- 6 years) completed screening tests and
five tasks including object manipulation, maximal pinch grip, flexion and
extension of the index finger (tremor assessment), maximal finger tapping
(movement speed and rhythmicity assessment), and the grooved pegboard test.
Force, acceleration, and/or first dorsal interosseus EMG were recorded during
four of the tasks. RESULTS: Task performance did not differ between groups.
Learning was evident on tasks with repeated trials and the magnitude of learning
did not differ between groups. CONCLUSIONS: Hand function, tremor, and task
learning were unaffected in RLS/WED patients. Patients manipulated objects in a
normal manner and exhibited normal movement speed, rhythmicity, and tremor.
SIGNIFICANCE: Further research is needed to assess other types of movement in
RLS/WED patients to gain insight into the motor circuitry affected and the
underlying pathophysiology.
PMID- 25113277
TI - Left lower lobe torsion following upper lobectomy-prompt recognition and
treatment improve survival.
AB - Lobar torsion is a rare but life-threatening complication after lung resection.
We report a case of left lower lobe torsion in 57-year-old women after upper
lobectomy for underlying lung cancer. Definitive diagnosis of lung torsion was
made at exploratory thoracotomy following abnormal chest radiography and
bronchoscopy on the first post-operative day. An emergency completion
pneumonectomy was performed and left lower lobe was resected. The post-operative
course was uncomplicated and patient was discharged home on the seventh post
operative day. Early recognition and prompt treatment of lobar torsion is
essential for preventing potentially catastrophic complications including fatal
gangrene of the pulmonary lobe.
PMID- 25113276
TI - Imbalance of von Willebrand factor and its cleaving protease ADAMTS13 during
systemic inflammation superimposed on advanced cirrhosis.
AB - BACKGROUND & AIMS: Systemic inflammation in advanced cirrhosis represents a
spectrum ranging from subclinical pathological bacterial translocation and immune
activation to overt bacterial infection and sepsis. We hypothesized that systemic
inflammation in cirrhosis is accompanied by a failure of ADAMTS13 to control the
prothrombotic function of von Willebrand factor (VWF), which is increased in
portal hypertension and hepatic fibrosis. METHODS: Patients with Child A
cirrhosis (n = 25), Child B/C cirrhosis without clinical features of systemic
inflammation (n = 31), and Child B/C cirrhosis with overt bacterial infections or
systemic inflammatory response syndrome (n = 24) were analysed for ADAMTS13 and
associated parameters and were followed to determine transplant-free survival.
RESULTS: Plasma concentration and activity of ADAMTS13 were decreased in patients
with systemic inflammation. Furthermore, ADAMTS13 inversely correlated with the
extent of bacterial translocation and the severity of acute-phase reaction. As a
function of reduced ADAMTS13 activity and increased VWF antigen, plasma from
patients with superimposed inflammation strongly aggregated the platelet receptor
glycoprotein Ib in presence of ristocetin. VWF:RCo correlated with higher
concentrations of leucocytes and lipopolysaccharide-binding protein, organ
dysfunction, augmented turnover of cross-linked intravascular fibrin, and the
occurrence of acute kidney injury during follow-up. VWF:RCo of 390% or more
predicted transplant-free survival in univariate analysis [HR = 8.24 (3.30
20.54)] and after adjustment for MELD [HR = 3.58 (1.30-9.88)]. However, adverse
outcome was not associated with the accumulation of high-molecular weight VWF
multimers. CONCLUSIONS: Systemic inflammation complicating advanced cirrhosis is
accompanied by reduced activity of ADAMTS13 promoting a prothrombotic function of
VWF, which can be employed to predict clinical outcome.
PMID- 25113278
TI - Optimizing the electrical energy conversion cycle of dielectric elastomer
generators.
AB - A strategy to control the electrical charge is developed to achieve high energy
density of soft dielectric elastomer generators for energy harvesting. The
strategy is analytically shown and experimentally demonstrated to produce the
highest energy density ever reported for a soft generator.
PMID- 25113275
TI - Conditions for enhancing the encoding of an elementary motor memory by rTMS.
AB - OBJECTIVE: Motor learning results in changes of movement representation in
primary motor cortex (M1) a process involving long-term potentiation (LTP).
Pairing motor training with repetitive transcranial magnetic stimulation (rTMS)
of M1 enhances the formation of a motor memory. Here we determined the effect of
pairing M1 stimulation and the execution of training movements at different times
and frequencies on the formation of a motor memory. METHODS: Formation of a motor
memory was defined as increases in motor evoked potentials (MEP) of the training
agonist (extensor carpi ulnaris muscle, ECU) and increases in peak acceleration
of the trained movements that last more than 60min. Training consisted of
auditory-paced ballistic wrist extension movements (30min, 0.5Hz) paired with
0.1, 0.25 or 0.5Hz subthreshold rTMS. The rTMS pulse was applied at either the
onset, 100ms prior to or 300ms after the onset of training movement related
increases in electromyographic (EMG) activity of ECU. This was compared to a Sham
condition. RESULTS: Only 0.1Hz rTMS applied at the onset of the training related
increase in ECU-EMG activity resulted in increases in MEP amplitudes and peak
acceleration when compared to the Sham. CONCLUSIONS: The formation of motor
memory is enhanced above the naive level by co-administration of low frequency
rTMS at the time of execution of training movements. SIGNIFICANCE: These results
indicate the importance of time and frequency of rTMS in these settings and
should be considered in the design of rehabilitation treatment strategies using
rTMS.
PMID- 25113280
TI - Elderly CML patients' treatment: considering not only physician's judgment but
also co-morbidity indexes.
PMID- 25113279
TI - Engineering of near infrared fluorescent proteinoid-poly(L-lactic acid) particles
for in vivo colon cancer detection.
AB - BACKGROUND: The use of near-infrared (NIR) fluorescence imaging techniques has
gained great interest for early detection of cancer owing to the negligible
absorption and autofluorescence of water and other intrinsic biomolecules in this
region. The main aim of the present study is to synthesize and characterize novel
NIR fluorescent nanoparticles based on proteinoid and PLLA for early detection of
colon tumors. METHODS: The present study describes the synthesis of new
proteinoid-PLLA copolymer and the preparation of NIR fluorescent nanoparticles
for use in diagnostic detection of colon cancer. These fluorescent nanoparticles
were prepared by a self-assembly process in the presence of the NIR dye
indocyanine green (ICG), a FDA-approved NIR fluorescent dye. Anti
carcinoembryonic antigen antibody (anti-CEA), a specific tumor targeting ligand,
was covalently conjugated to the P(EF-PLLA) nanoparticles through the surface
carboxylate groups using the carbodiimide activation method. RESULTS AND
DISCUSSION: The P(EF-PLLA) nanoparticles are stable in different conditions, no
leakage of the encapsulated dye into PBS containing 4% HSA was detected. The
encapsulation of the NIR fluorescent dye within the P(EF-PLLA) nanoparticles
improves significantly the photostability of the dye. The fluorescent
nanoparticles are non-toxic, and the biodistribution study in a mouse model
showed they evacuate from the body over 24 h. Specific colon tumor detection in a
chicken embryo model and a mouse model was demonstrated for anti-CEA-conjugated
NIR fluorescent P(EF-PLLA) nanoparticles. CONCLUSIONS: The results of this study
suggest a significant advantage of NIR fluorescence imaging using NIR fluorescent
P(EF-PLLA) nanoparticles over colonoscopy. In future work we plan to broaden this
study by encapsulating cancer drugs such as paclitaxel and/or doxorubicin, within
these biodegradable NIR fluorescent P(EF-PLLA) nanoparticles, for both detection
and therapy of colon cancer.
PMID- 25113281
TI - [Steppage gait in a 10 year-old girl].
PMID- 25113283
TI - Evaluating the implementation of a school-based emotional well-being programme: a
cluster randomized controlled trial of Zippy's Friends for children in
disadvantaged primary schools.
AB - Schools are recognized as one of the most important settings for promoting social
and emotional well-being among children and adolescents. This clustered
randomized controlled trial evaluated Zippy's Friends, an international school
based emotional well-being programme, with 766 children from designated
disadvantaged schools. The purpose of this study was to evaluate the immediate
and long term impact of the programme and to determine the impact of
implementation fidelity on programme outcomes. Teachers reported emotional
literacy outcomes using the Emotional Literacy Checklist, and emotional and
behavioural outcomes using the Strengths and Difficulties Questionnaire.
Controlling for the hierarchical structure of the data, path analysis using
structural equation modelling revealed that the programme had a significant
positive impact on the children's emotional literacy scores including significant
improvements in the subscale scores of self-awareness (P < 0.001), self
regulation (P < 0.01), motivation (P < 0.001) and social skills (P < 0.001) at
post-intervention. These results were maintained at 12-month follow-up (P <
0.01). The programme, however, did not have a significant impact on children's
emotional and behavioural problems. Analysis of programme fidelity indicated that
high fidelity was directly related to improved emotional literacy scores at post
intervention.
PMID- 25113284
TI - Antifreeze effect of carboxylated epsilon-poly-L-lysine on the growth kinetics of
ice crystals.
AB - Some biological substances control the nucleation and growth of inorganic
crystals. Antifreeze proteins, which prohibit ice crystal growth in living
organisms, promise are also important as biological antifreezes for medical
applications and in the frozen food industries. In this work, we investigated the
crystallization of ice in the presence of a new cryoprotector, carboxylated
epsilon-poly-L-lysine (COOH-PLL). In order to reveal the characteristics and the
mechanism of its antifreeze effect, free-growth experiments of ice crystals were
carried out in solutions with various COOH-PLL concentrations and degrees of
supercooling, and the depression of the freezing point and growth rates of the
tips of ice dendrites were obtained using optical microscopy. Hysteresis of
growth rates and depression of the freezing point was revealed in the presence of
COOH-PLL. The growth-inhibition effect of COOH-PLL molecules could be explained
on the basis of the Gibbs-Thomson law and the use of Langmuir's adsorption
isotherm. Theoretical kinetic curves for hysteresis calculated on the basis of
Punin-Artamonova's model were in good agreement with experimental data. We
conclude that adsorption of large biological molecules in the case of ice
crystallization has a non-steady-state character and occurs more slowly than the
process of embedding of crystal growth units.
PMID- 25113286
TI - Self-compassion moderates the relationship between body mass index and both
eating disorder pathology and body image flexibility.
AB - The current study examined whether self-compassion, the tendency to treat oneself
kindly during distress and disappointments, would attenuate the positive
relationship between body mass index (BMI) and eating disorder pathology, and the
negative relationship between BMI and body image flexibility. One-hundred and
fifty-three female undergraduate students completed measures of self-compassion,
self-esteem, eating disorder pathology, and body image flexibility, which refers
to one's acceptance of negative body image experiences. Controlling for self
esteem, hierarchical regressions revealed that self-compassion moderated the
relationships between BMI and the criteria. Specifically, the positive
relationship between BMI and eating disorder pathology and the negative
relationship between BMI and body image flexibility were weaker the higher
women's levels of self-compassion. Among young women, self-compassion may help to
protect against the greater eating disturbances that coincide with a higher BMI,
and may facilitate the positive body image experiences that tend to be lower the
higher one's BMI.
PMID- 25113287
TI - Body image and personality among British men: associations between the Big Five
personality domains, drive for muscularity, and body appreciation.
AB - The present study examined associations between the Big Five personality domains
and measures of men's body image. A total of 509 men from the community in
London, UK, completed measures of drive for muscularity, body appreciation, the
Big Five domains, and subjective social status, and provided their demographic
details. The results of a hierarchical regression showed that, once the effects
of participant body mass index (BMI) and subjective social status had been
accounted for, men's drive for muscularity was significantly predicted by
Neuroticism (beta=.29). In addition, taking into account the effects of BMI and
subjective social status, men's body appreciation was significantly predicted by
Neuroticism (beta=-.35) and Extraversion (beta=.12). These findings highlight
potential avenues for the development of intervention approaches based on the
relationship between the Big Five personality traits and body image.
PMID- 25113288
TI - Herpes PCR testing and empiric acyclovir use beyond the neonatal period.
AB - BACKGROUND: Diagnostic strategies based on empirical testing and treatment to
identify herpes simplex virus (HSV) infection in neonates may not be appropriate
for older children in whom the most common presentation of severe infection is
encephalitis, a rare and clinically recognizable condition. METHODS: Use of
acyclovir in infants and children in 6 common non-HSV infection-related diagnosis
related groups was characterized between 1999 and 2012 at 15 US pediatric
hospitals by using the Pediatric Health Information System database.
Characteristics of non-neonatal patients at 1 institution tested for HSV
encephalitis over a 6.5-year period were then analyzed to identify factors
associated with potentially unnecessary testing and treatment. RESULTS: Acyclovir
use increased from 7.6% to 15.6% (P < .001) from 1999 to 2012. Much of this
increase came in infants 30 to 60 days of age (82.7% increase, P < .001) and in
patients with milder disease severity (44.8% increase, P < .001). Length of stay
was increased by 2 days for children treated with acyclovir (P < .001). At our
institution, 1394 HSV cerebrospinal fluid polymerase chain reactions were
performed in children >30 days old, with only 3 positive results (0.22%).
Comparison of the 3 subjects with positive testing and 55 with negative testing
revealed that all cases, but only 4% (95% confidence interval 1.2%-14.0%) of
noncases had clinical characteristics typical of HSV encephalitis. CONCLUSIONS:
Strategies for diagnosis and empirical treatment of suspected HSV encephalitis
beyond the neonatal period have trended toward the approach common for neonates
without evidence of an increase in disease incidence. This may result in
increased medical costs and risk to patients.
PMID- 25113289
TI - Mild prematurity, proximal social processes, and development.
AB - OBJECTIVE: To elucidate the role of gestational age in determining the risk of
poor developmental outcomes among children born late preterm (34-36 weeks) and
early term (37-38 weeks) versus full term (39-41 weeks) by examining the
contribution of gestational age to these outcomes in the context of proximal
social processes. METHODS: This was an analysis of the Canadian National
Longitudinal Survey of Children and Youth. Developmental outcomes were examined
at 2 to 3 (N= 15099) and 4 to 5 years (N= 12302). The sample included singletons,
delivered at 34 to 41 weeks, whose respondents were their biological mothers.
Multivariable modified Poisson regression was used to directly estimate adjusted
relative risks (aRRs). We assessed the role of parenting by using moderation
analyses. RESULTS: In unadjusted analyses, children born late preterm appeared to
have greater risk for developmental delay (relative risk = 1.26; 95% confidence
interval [CI], 1.01 to 1.56) versus full term. In adjusted analyses, results were
nonsignificant at 2 to 3 years (late preterm aRR = 1.13; 95% CI, 0.90 to 1.42;
early term aRR = 1.11; 95% CI, 0.96 to 1.27) and 4 to 5 years (late preterm aRR =
1.06; 95% CI, 0.79 to 1.43; early term aRR = 1.03; 95% CI, 0.85 to 1.25).
Parenting did not modify the effect of gestational age but was a strong predictor
of poor developmental outcomes. CONCLUSIONS: Our findings show that, closer to
full term, social factors (not gestational age) may be the most important
influences on development.
PMID- 25113290
TI - Cognitive delay and behavior problems prior to school age.
AB - OBJECTIVE: To investigate the relationship between cognitive delay (CD) and
behavior problems between ages 9 months and 5 years, while adjusting for
covariates related to CD. METHODS: Data were from 4 waves of the Early Childhood
Longitudinal Study, Birth Cohort (n = 8000). Children were classified as
typically developing (TD) or as having resolved, newly developed, or persistent
CD between 9 and 24 months, based on scores from the Bayley Short Form-Research
Edition below or above the 10th percentile. Child behavior was measured by using
the Infant/Toddler Symptom Checklist (ages 9 and 24 months) and the Preschool and
Kindergarten Behavior Scales (ages 4 and 5 years); children in the top 10th
percentile were considered to have a behavior problem. Hierarchical linear
modeling estimated the effect of CD status on children's behavioral trajectories,
adjusted for confounders. RESULTS: CD resolved for 80.3% of children between 9
and 24 months. Behavior problems at 24 months were detected in 19.3%, 21.8%, and
35.5% of children with resolved, newly developed, and persistent CD,
respectively, versus 13.0% of TD children. Behavior problems increased among
children with CD over time, and more so among children with persistent CD. By age
5, children with persistent CD had behavior scores moderately (0.59 SD) higher
than TD children. CONCLUSIONS: Behavior problems among children with CD are
slightly higher at 9 months, clearly evident by 24 months, and increase as
children move toward school age. Efforts to promote the earliest identification,
evaluation, and service referral may be necessary to improve outcomes for these
children.
PMID- 25113291
TI - Variation in emergency department admission rates in US children's hospitals.
AB - OBJECTIVE: To measure the hospital-level variation in admission rates for
children receiving treatment of common pediatric illnesses across emergency
departments (EDs) in US children's hospitals. METHODS: We performed a multi
center cross sectional study of children presenting to the EDs of 35 pediatric
tertiary-care hospitals participating in the Pediatric Health Information System
(PHIS). Admission rates were calculated for visits occurring between January 1,
2009, and December 31, 2012, associated with 1 of 7 common conditions, and
corrected to adjust for hospital-level severity of illness. Conditions were
selected systematically based on frequency of visits and admission rates.
RESULTS: A total of 1288706 ED encounters (13.8% of all encounters) were
associated with 1 of the 7 conditions of interest. After adjusting for hospital
level severity, the greatest variation in admission rates was observed for
concussion (range 5%-72%), followed by pneumonia (19%-69%), and bronchiolitis
(19%-65%). The least variation was found among patients presenting with seizures
(7%-37%) and kidney and urinary tract infections (6%-37%). Although variability
existed in disease-specific admission rates, certain hospitals had consistently
higher, and others consistently lower, admission rates. CONCLUSIONS: We observed
greater than threefold variation in severity-adjusted admission rates for common
pediatric conditions across US children's hospitals. Although local practices and
hospital-level factors may partly explain this variation, our findings highlight
the need for greater focus on the standardization of decisions regarding
admission.
PMID- 25113292
TI - Impact locations and concussion outcomes in high school football player-to-player
collisions.
AB - BACKGROUND: Little research has examined concussion outcomes in terms of impact
location (ie, the area on the head in which the impact occurred). This study
describes the epidemiology of concussions resulting from player-to-player
collision in high school football by impact location. METHODS: National High
School Sports-Related Injury Surveillance Study data (2008/2009-2012/2013) were
analyzed to calculate rates and describe circumstances of football concussion
(eg, symptomology, symptom resolution time, return to play) resulting from player
to-player collisions by impact location (ie, front-, back-, side-, and top-of-the
head). RESULTS: Most concussions resulting from player-to-player collisions
occurred from front-of-the-head (44.7%) and side-of-the-head (22.3%) impacts.
Number of symptoms reported, prevalence of reported symptoms, symptom resolution
time, and length of time to return to play were not associated with impact
location. However, a larger proportion of football players sustaining concussions
from top-of-the-head impacts experienced loss of consciousness (8.0%) than those
sustaining concussions from impacts to other areas of the head (3.5%) (injury
proportion ratio 2.3; 95% confidence interval 1.2-4.2; P = .008). Players had
their head down at the time of impact in a higher proportion of concussions
caused by top-of-the-head impacts (86.4%) than concussions from impacts to other
areas of the head (24.0%) (injury proportion ratio 3.6; 95% confidence interval
3.2-4.0; P < .001). CONCLUSIONS: Among high school football players who sustained
concussions due to player-to-player collisions, concussion outcomes were
generally independent of impact location. Recommended strategies for reducing the
proportion of top-of-the-head impacts include improved education regarding
tackling with proper "head-up" technique.
PMID- 25113293
TI - Reducing catheter-associated urinary tract infections: a quality-improvement
initiative.
AB - BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are among the
most common health care-associated infections in the United States, yet little is
known about the prevention and epidemiology of pediatric CAUTIs. METHODS: An
observational study was conducted to assess the impact of a CAUTI quality
improvement prevention bundle that included institution-wide standardization of
and training on urinary catheter insertion and maintenance practices, daily
review of catheter necessity, and rapid review of all CAUTIs. Poisson regression
was used to determine the impact of the bundle on CAUTI rates. A retrospective
cohort study was performed to describe the epidemiology of incident pediatric
CAUTIs at a tertiary care children's hospital over a 3-year period (June 2009 to
June 2012). RESULTS: Implementation of the CAUTI prevention bundle was associated
with a 50% reduction in the mean monthly CAUTI rate (95% confidence interval:
1.28 to -0.12; P = .02) from 5.41 to 2.49 per 1000 catheter-days. The median
monthly catheter utilization ratio remained unchanged; ~90% of patients had an
indication for urinary catheterization. Forty-four patients experienced 57 CAUTIs
over the study period. Most patients with CAUTIs were female (75%), received care
in the pediatric or cardiac ICUs (70%), and had at least 1 complex chronic
condition (98%). Nearly 90% of patients who developed a CAUTI had a recognized
indication for initial catheter placement. CONCLUSIONS: CAUTI is a common
pediatric health care-associated infection. Implementation of a prevention bundle
can significantly reduce CAUTI rates in children.
PMID- 25113294
TI - Neuroinvasive arboviral disease in the United States: 2003 to 2012.
AB - OBJECTIVE: To describe the epidemiologic and clinical syndromes associated with
pediatric neuroinvasive arboviral infections among children in the United States
from 2003 through 2012. METHODS: We reviewed data reported by state health
departments to ArboNET, the national arboviral surveillance system, for 2003
through 2012. Children (<18 years) with neuroinvasive arboviral infections (eg,
meningitis, encephalitis, or acute flaccid paralysis) were included. Demographic,
clinical syndrome, outcome, geographic, and temporal data were analyzed for all
cases. RESULTS: During the study period, 1217 cases and 22 deaths due to
pediatric neuroinvasive arboviral infection were reported from the 48 contiguous
states. La Crosse virus (665 cases; 55%) and West Nile virus (505 cases; 41%)
were the most common etiologies identified. Although less common, Eastern equine
encephalitis virus (30 cases; 2%) resulted in 10 pediatric deaths. La Crosse
virus primarily affected younger children, whereas West Nile virus was more
common in older children and adolescents. West Nile virus disease cases occurred
throughout the country, whereas La Crosse and the other arboviruses were more
focally distributed. CONCLUSIONS: Neuroinvasive arboviral infections were an
important cause of pediatric disease from 2003 through 2012. Differences in the
epidemiology and clinical disease result from complex interactions among virus,
vector, host, and the environment. Decreasing the morbidity and mortality from
these agents depends on vector control, personal protection to reduce mosquito
and tick bites, and blood donor screening. Effective surveillance is critical to
inform clinicians and public health officials about the epidemiologic features of
these diseases and to direct prevention efforts.
PMID- 25113296
TI - Identifying very preterm children at educational risk using a school readiness
framework.
AB - OBJECTIVES: Children born very preterm (VPT) are at high risk of educational
delay, yet few guidelines exist for the early identification of those at greatest
risk. Using a school readiness framework, this study examined relations between
preschool neurodevelopmental functioning and educational outcomes to age 9 years.
METHODS: The sample consisted of a regional cohort of 110 VPT (<= 32 weeks'
gestation) and 113 full-term children born during 1998-2000. At corrected age 4
years, children completed a multidisciplinary assessment of their health/motor
development, socioemotional adjustment, core learning skills, language, and
general cognition. At ages 6 and 9, children's literacy and numeracy skills were
assessed using the Woodcock-Johnson III Tests of Achievement. RESULTS: Across all
readiness domains, VPT children were at high risk of delay/impairment (odds
ratios 2.5-3.5). Multiple problems were also more common (47% vs 16%). At follow
up, almost two-thirds of VPT children were subject to significant educational
delay in either literacy, numeracy or both compared with 29% to 31% of full-term
children (odds ratios 3.4-4.4). The number of readiness domains affected at age 4
strongly predicted later educational risk, especially when multiple problems were
present. Receiver operating characteristic analysis confirmed >= 2 readiness
problems as the optimal threshold for identifying VPT children at educational
risk. CONCLUSIONS: School readiness offers a promising framework for the early
identification of VPT children at high educational risk. Findings support the
utility of >= 2 affected readiness domains as an effective criterion for referral
for educational surveillance and/or additional support during the transition to
school.
PMID- 25113297
TI - Children in hospitals before there were children's hospitals.
PMID- 25113299
TI - Evidence-based standardization and ED admission rate variation in US children's
hospitals.
PMID- 25113298
TI - Defining and determining medical necessity in Medicaid managed care.
AB - OBJECTIVES: In 2013, the American Academy of Pediatrics published a policy
statement calling for pediatricians to be informed about the need for specific
pediatric medical necessity language because children deserve "the intent
embedded in Medicaid." This study aims to explore the definitions and
determinations of medical necessity in Medicaid Managed Care (MMC), document the
relevant language used throughout Medicaid, and investigate whether the federal
standard of medical necessity for children is replicated in related state
documents. METHODS: We conducted a desk review of state statutes, model MMC
contracts, and 2 provider manuals per state, for 33 states with a full-risk MMC
model. RESULTS: The federal "to correct and ameliorate" standard was replicated
in 100% of state regulations, 72% of MMC model contracts (n = 13 of 18 MMC model
contracts available online), and 54% of provider manuals (n = 30 of 56 available
and sampled online). Only 9 states had an explicit "preventive" pediatric medical
necessity standard in their state regulations that exemplified "the intent
imbedded in Medicaid." CONCLUSIONS: The federal medical necessity standard for
children is not replicated consistently within MMC programs from the state, to
health plans, to network providers. Although the majority of the documents
reviewed included the standard, the presence of the standard decreased by almost
half between state-level and network-provider-level regulations. Having a single,
explicitly defined pediatric medical necessity definition replicated at all
levels of the health system would reduce confusion and increase the ability of
pediatricians to apply the standard more uniformly.
PMID- 25113300
TI - Tachypnea of infancy as the first sign of Sanfilippo syndrome.
AB - This report describes the first known case of Mucopolysaccharidosis type IIIA
presenting with respiratory symptoms and characteristic lung pathology. This case
highlights under-recognized areas of systemic involvement and earlier modes of
presentation in lysosomal storage disorders as well as the importance of
investigating infants who have persistent tachypnea.
PMID- 25113295
TI - Autosomal recessive polycystic kidney disease: a hepatorenal fibrocystic disorder
with pleiotropic effects.
AB - Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of
chronic kidney disease in children. The care of ARPKD patients has traditionally
been the realm of pediatric nephrologists; however, the disease has multisystem
effects, and a comprehensive care strategy often requires a multidisciplinary
team. Most notably, ARPKD patients have congenital hepatic fibrosis, which can
lead to portal hypertension, requiring close follow-up by pediatric
gastroenterologists. In severely affected infants, the diagnosis is often first
suspected by obstetricians detecting enlarged, echogenic kidneys and
oligohydramnios on prenatal ultrasounds. Neonatologists are central to the care
of these infants, who may have respiratory compromise due to pulmonary hypoplasia
and massively enlarged kidneys. Surgical considerations can include the
possibility of nephrectomy to relieve mass effect, placement of dialysis access,
and kidney and/or liver transplantation. Families of patients with ARPKD also
face decisions regarding genetic testing of affected children, testing of
asymptomatic siblings, or consideration of preimplantation genetic diagnosis for
future pregnancies. They may therefore interface with genetic counselors,
geneticists, and reproductive endocrinologists. Children with ARPKD may also be
at risk for neurocognitive dysfunction and may require neuropsychological
referral. The care of patients and families affected by ARPKD is therefore a
multidisciplinary effort, and the general pediatrician can play a central role in
this complex web of care. In this review, we outline the spectrum of clinical
manifestations of ARPKD and review genetics of the disease, clinical and genetic
diagnosis, perinatal management, management of organ-specific complications, and
future directions for disease monitoring and potential therapies.
PMID- 25113301
TI - Subdural hemorrhages associated with antithrombotic therapy in infants with
cerebral atrophy.
AB - Low-molecular-weight heparins, such as enoxaparin, are often used to treat
thrombosis in infants. We present 4 infants with diffuse brain injury who
developed cerebral venous sinus thrombosis or deep vein thrombosis and were
treated with enoxaparin. These infants subsequently developed subdural
hemorrhages, and enoxaparin was stopped. In 3 cases, the subdural hemorrhages
were found on routine surveillance brain MRI, and in 1 case imaging was urgently
obtained because of focal seizures. Two patients needed urgent neurosurgical
intervention, and all subdural hemorrhages improved or resolved on follow-up
imaging. Each infant developed severe neurologic deficits, probably from the
coexisting diffuse brain injury rather than from the subdural hemorrhages
themselves. The risk of intracranial hemorrhage from enoxaparin may be
accentuated in patients with diffuse brain injury, and careful consideration
should be given before treatment in this population.
PMID- 25113302
TI - Hospitalizations for severe lower respiratory tract infections.
AB - BACKGROUND: Hospitalization for lower respiratory tract infections (LRTIs) among
children have been well characterized. We characterized hospitalizations for
severe LRTI among children. METHODS: We analyzed claims data from commercial and
Medicaid insurance enrollees (MarketScan) ages 0 to 18 years from 2007 to 2011.
LRTI hospitalizations were identified by the first 2 listed International
Classification of Diseases, Ninth Revision discharge codes; those with ICU
admission and/or receiving mechanical ventilation were defined as severe LRTI.
Underlying conditions were determined from out- and inpatient discharge codes in
the preceding year. We report insurance specific and combined rates that used
both commercial and Medicaid rates and adjusted for age and insurance status.
RESULTS: During 2007-2011, we identified 16797 and 12053 severe LRTI
hospitalizations among commercial and Medicaid enrollees, respectively. The rates
of severe LRTI hospitalizations per 100000 person-years were highest in children
aged <1 year (commercial: 244; Medicaid: 372, respectively), and decreased with
age. Among commercial enrollees, >= 1 condition increased the risk for severe
LRTI (1 condition: adjusted relative risk, 2.68; 95% confidence interval, 2.58
2.78; 3 conditions: adjusted relative risk, 4.85; 95% confidence interval, 4.65
5.07) compared with children with no medical conditions. Using
commercial/Medicaid combined rates, an estimated 31289 hospitalizations for
severe LRTI occurred each year in children in the United States. CONCLUSIONS:
Among children, the burden of hospitalization for severe LRTI is greatest among
children aged <1 year. Children with underlying medical conditions are at
greatest risk for severe LRTI hospitalization.
PMID- 25113303
TI - Small geographic area variations in prescription drug use.
AB - BACKGROUND: Despite the frequency of pediatric prescribing little is known about
practice differences across small geographic regions and payer type (Medicaid and
commercial). OBJECTIVE: The goal of this research was to quantify variation in
prescription drug use among northern New England children. METHODS: Northern New
England, all-payer administrative data (2007-2010) permitted study of
prescriptions for 949 821 children ages 0 to 17 years (1.75 million person-years
[PYs]; 54% Medicaid, 46% commercial). Age- and gender adjusted overall and drug
group-specific prescription use was quantified according to payer type (Medicaid
or commercial) and within payer type across 69 hospital service areas (HSAs). We
measured prescription fills per PY (rate) and annual, mean percentage of the
population with any drug group-specific fills (prevalence). RESULTS: Overall mean
annual prescriptions per PY were 3.4 (commercial) and 5.5 (Medicaid). Generally,
these payer type differences were smaller than HSA-level variation within payer
type. HSA-level rates of attention-deficit/hyperactivity disorder drug use (5th
95th percentile) varied twofold in Medicaid and more than twofold in commercially
insured children; HSA-level antidepressant use varied more than twofold within
each payer type. Antacid use varied threefold across HSAs and was highest in
infants where commercial use paradoxically exceeded Medicaid. Prevalence of drug
use varied as much as rates across HSAs. CONCLUSIONS: Prescription use was higher
among Medicaid-insured than commercially insured children. Regional variation
generally exceeded payer type differences, especially for drugs used in
situations of diagnostic and therapeutic uncertainty. Efforts should advance best
pediatric prescribing discussions and shared decision-making.
PMID- 25113305
TI - Characterization of a partial exon 9/intron 9 deletion in the coagulation factor
XII gene (F12) detected in two Turkish families with hereditary angioedema and
normal C1 inhibitor.
PMID- 25113304
TI - The diagnosis and management of von Willebrand disease: a United Kingdom
Haemophilia Centre Doctors Organization guideline approved by the British
Committee for Standards in Haematology.
PMID- 25113306
TI - US lung cancer trends by histologic type.
AB - BACKGROUND: Lung cancer incidence rates overall are declining in the United
States. This study investigated the trends by histologic type and demographic
characteristics. METHODS: Surveillance, Epidemiology, and End Results (SEER)
program rates of microscopically confirmed lung cancer overall and squamous cell,
small cell, adenocarcinoma, large cell, other, and unspecified carcinomas among
US whites and blacks diagnosed from 1977 to 2010 and white non-Hispanics,
Asian/Pacific Islanders, and white Hispanics diagnosed from 1992 to 2010 were
analyzed by sex and age. RESULTS: Squamous and small cell carcinoma rates
declined since the 1990s, although less rapidly among females than males.
Adenocarcinoma rates decreased among males and only through 2005, after which
they then rose during 2006 to 2010 among every racial/ethnic/sex group; rates for
unspecified type declined. Male/female rate ratios declined among whites and
blacks more than among other groups. Recent rates among young females were higher
than among males for adenocarcinoma among all racial/ethnic groups and for other
specified carcinomas among whites. CONCLUSIONS: US lung cancer trends vary by
sex, histologic type, racial/ethnic group, and age, reflecting historical
cigarette smoking rates, duration, cessation, cigarette composition, and exposure
to other carcinogens. Substantial excesses among males have diminished and higher
rates of adenocarcinoma among young females have emerged as rates among males
declined more rapidly. The recognition of EGFR mutation and ALK rearrangements
that occur primarily in adenocarcinomas are the primary basis for the molecular
revolution that has transformed lung cancer diagnosis and treatment over the past
decade, and these changes have affected recent type-specific trends.
PMID- 25113307
TI - [Placebo analgesia and sleep].
AB - The placebo response is a psychobiological phenomenon for clinical benefits
following the administration of an inert substance whatever its form. This
phenomenon can be attributed to a wide range of neurobiological processes, such
as expectations of relief, the Pavlovian conditioning and learning, emotional
regulation, and reward mechanisms, which are themselves under the influence of
processes that take place during sleep. The study of placebo analgesia in healthy
from a placebo conditioning associated with analgesic suggestions has highlighted
a relationship between sleep, expectations of relief and placebo analgesia: when
the induction is persuasive before sleep, expectations of relief modulate placebo
response the next morning and paradoxical sleep correlates negatively with both
expectations and the placebo response. When the analgesic experience before sleep
is less persuasive, expectations of relief are still present but no longer
interact with placebo analgesia while paradoxical sleep no longer correlates with
the analgesic placebo response. Sleep-processes especially during paradoxical
sleep seem to influence the relationship between expectations of relief and
placebo analgesia. In this review, we describe the relationship between sleep and
placebo analgesia, the mechanisms involved in the placebo response (e.g.,
conditioning, learning, memory, reward) and their potential link with sleep that
could make it a special time for the building placebo response.
PMID- 25113309
TI - Physical and chemical stability of proflavine contrast agent solutions for early
detection of oral cancer.
AB - BACKGROUND AND PURPOSE: Proflavine hemisulfate solution is a fluorescence
contrast agent to visualize cell nuclei using high-resolution optical imaging
devices such as the high-resolution microendoscope. These devices provide real
time imaging to distinguish between normal versus neoplastic tissue. These images
could be helpful for early screening of oral cancer and its precursors and to
determine accurate margins of malignant tissue for ablative surgery.
Extemporaneous preparation of proflavine solution for these diagnostic procedures
requires preparation in batches and long-term storage to improve compounding
efficiency in the pharmacy. However, there is a paucity of long-term stability
data for proflavine contrast solutions. METHODS: The physical and chemical
stability of 0.01% (10 mg/100 ml) proflavine hemisulfate solutions prepared in
sterile water was determined following storage at refrigeration (4-8C) and room
temperature (23C). Concentrations of proflavine were measured at predetermined
time points up to 12 months using a validated stability-indicating high
performance liquid chromatography method. RESULTS: Proflavine solutions stored
under refrigeration were physically and chemically stable for at least 12 months
with concentrations ranging from 95% to 105% compared to initial concentration.
However, in solutions stored at room temperature increased turbidity and
particulates were observed in some of the tested vials at 9 months and 12 months
with peak particle count reaching 17-fold increase compared to baseline.
Solutions stored at room temperature were chemically stable up to six months (94
105%). CONCLUSION: Proflavine solutions at concentration of 0.01% were chemically
and physically stable for at least 12 months under refrigeration. The solution
was chemically stable for six months when stored at room temperature. We
recommend long-term storage of proflavine solutions under refrigeration prior to
diagnostic procedure.
PMID- 25113310
TI - Removal of trace organic chemicals and performance of a novel hybrid
ultrafiltration-osmotic membrane bioreactor.
AB - A hybrid ultrafiltration-osmotic membrane bioreactor (UFO-MBR) was investigated
for over 35 days for nutrient and trace organic chemical (TOrC) removal from
municipal wastewater. The UFO-MBR system uses both ultrafiltration (UF) and
forward osmosis (FO) membranes in parallel to simultaneously extract clean water
from an activated sludge reactor for nonpotable (or environmental discharge) and
potable reuse, respectively. In the FO stream, water is drawn by osmosis from
activated sludge through an FO membrane into a draw solution (DS), which becomes
diluted during the process. A reverse osmosis (RO) system is then used to
reconcentrate the diluted DS and produce clean water suitable for direct potable
reuse. The UF membrane extracts water, dissolved salts, and some nutrients from
the system to prevent their accumulation in the activated sludge of the osmotic
MBR. The UF permeate can be used for nonpotable reuse purposes (e.g., irrigation
and toilet flushing). Results from UFO-MBR investigation illustrated that the
chemical oxygen demand, total nitrogen, and total phosphorus removals were
greater than 99%, 82%, and 99%, respectively. Twenty TOrCs were detected in the
municipal wastewater that was used as feed to the UFO-MBR system. Among these 20
TOrCs, 15 were removed by the hybrid UFO-MBR system to below the detection limit.
High FO membrane rejection was observed for all ionic and nonionic hydrophilic
TOrCs and lower rejection was observed for nonionic hydrophobic TOrCs. With the
exceptions of bisphenol A and DEET, all TOrCs that were detected in the DS were
well rejected by the RO membrane. Overall, the UFO-MBR can operate sustainably
and has the potential to be utilized for direct potable reuse applications.
PMID- 25113311
TI - Confidence and impact on clinical decision-making and behaviour in the emergency
department.
AB - BACKGROUND: Clinical competency is underpinned by the self-confidence of nurses
to act. Confidence may be critical to the understanding of how practice choices
are made and not made by nurses in extended practice roles. The aim of this study
was to explore how emergency nurses perceived (i) self-confidence in undertaking
an extended practice role; and (ii) the factors associated with confidence within
clinical practice. METHODS: A multicentred qualitative exploratory study. Fifty
two participants were included in the study. Across three sites 36 (28 females, 8
males) face to face interviews and 16 non-participant observations (13 females, 3
males) were conducted. RESULTS: The study generated new knowledge about self
confidence, self-efficacy and the role that contextual factors have in regulating
behaviour. It shows that self-confidence is an important resource that sustains a
nurse's ability to problem solve and to critically think in order to determine
how best to act. CONCLUSIONS: The development of self-confidence is important if
we are to promote effective clinical decision-making. Education programmes need
to identify strategies that can promote and support the development of self
confidence and resilience.
PMID- 25113312
TI - Shortfalls in residents' transfer documentation: challenges for emergency
department staff.
AB - BACKGROUND: Increasing numbers of residents are transferred from aged care
facilities to emergency departments. Frequently, residents arrive with inadequate
documentation regarding their presenting complaint or medical history, making it
difficult for emergency department staff to make decisions about care. METHODS: A
retrospective review of emergency department records was undertaken for residents
transferred from residential aged care facilities to two emergency departments in
Melbourne, Victoria in 2012. RESULTS: 2880 resident transfers were included in
the sample, of which 408 transfers were randomly selected for documentation
review. Clinically important documentation was frequently absent including: the
reason for transfer to the ED (n=197, 48.2%); baseline cognitive function (n=244,
59.7%); and vital signs at time of complaint (n=285, 69.9%). When the reason for
transfer was absent, residents with an altered conscious state had more
investigations and spent longer in the emergency department than when the reason
for transfer was recorded. CONCLUSION: Inadequate documentation negatively
impacted the resident's journey through the emergency department. There is
evidence that inadequate documentation contributes to poor patient outcomes. To
minimise the gaps in the transfer documentation regular staff development and
quality assurance programs may be required in residential aged care facilities.
PMID- 25113308
TI - Biology of advanced uveal melanoma and next steps for clinical therapeutics.
AB - Uveal melanoma is the most common intraocular malignancy although it is a rare
subset of all melanomas. Uveal melanoma has distinct biology relative to
cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed
with a primary uveal melanoma can be stratified for risk of metastasis by
cytogenetics or gene expression profiling, with approximately half of patients
developing metastatic disease, predominately hepatic in location, over a 15-yr
period. Historically, no systemic therapy has been associated with a clear
clinical benefit for patients with advanced disease, and median survival remains
poor. Here, as a joint effort between the Melanoma Research Foundation's ocular
melanoma initiative, CURE OM and the National Cancer Institute, the current
understanding of the molecular and immunobiology of uveal melanoma is reviewed,
and on-going laboratory research into the disease is highlighted. Finally, recent
investigations relevant to clinical management via targeted and immunotherapies
are reviewed, and next steps in the development of clinical therapeutics are
discussed.
PMID- 25113313
TI - Remote community-based public health nursing during a disaster: an ethnographic
case study in Japan.
AB - BACKGROUND: The Great East Japan Earthquake that occurred on March 11, 2011
generated a tsunami that directly struck Japan. Public health nurses (PHNs)
played important roles in this disaster response and community recovery. This
research identified a PHN's experience in an affected area. METHODS: An
ethnographic case study approach was used to obtain in-depth information
regarding the experiences of one PHN, using semi-structured interviews,
participant observation, and statistical documents. RESULTS: Six themes were
identified and explored, including that the PHN undertook overwhelming
responsibilities to protect the local residents, made several autonomous
decisions, and had a strong sense of mission. These were based on the
relationship-building that occurred with the local residents due to the
geographical characteristics and her own preparations. CONCLUSIONS: The findings
encourage PHNs to participate in simulations of disasters in preparation for
major catastrophes and establish good collaborative efforts with residents by
being a part of the community.
PMID- 25113314
TI - Patient perceptions of emergency department fast track: a prospective pilot study
comparing two models of care.
AB - BACKGROUND: Emergency department (ED) fast track has been shown to improve
patient flow for low complexity presentations.(1) The optimal model of care and
service delivery for fast track patients has not been established. AIMS: The
objective of this pilot study was to compare patient satisfaction using two
models of ED fast track - one in a tertiary hospital emergency department staffed
by doctors and the other in a nearby urban district hospital staffed by nurse
practitioners. We also wanted to determine the proportion of fast track patients
who would prefer to see a General Practitioner (GP) instead of presenting to the
ED. This pilot study was the foundation for subsequent studies later conducted by
Dinh et al.(2,3) METHODS: This was an observational study using a convenience
sample of patients. Eligible fast track patients were asked to complete a
standardised satisfaction survey. Presenting problems and waiting times of
patients were collected using patient information systems. Primary outcome
measure was satisfaction rating using a 5-point Likert scale. Secondary outcomes
were surrogate satisfaction measures encompassing questions on likelihood of
returning to ED. A multivariate analysis was performed to obtain odds ratio for
higher satisfaction scores. RESULTS: In total, 353 patients were recruited: 212
patients in the doctor treated group (DR) and 141 were in the nurse practitioner
treated group (NP). The two groups had similar baseline characteristics in terms
of age, gender, referral source and waiting times. Overall, 320/353(86%) patients
rated their care as either very good or excellent, with only 0.6% rating their
care as poor. Satisfaction scores in the NP group were higher than those in the
DR group (median score 4 vs. 3, p<0.01). A greater proportion of patients in the
NP group reported that they would return to the ED for a similar problem (99% vs.
91% p<0.01). Overall, 175/353 (50%) of patients indicated that they would prefer
to see a general practitioner for a similar problem if available nearby. These
numbers were slightly lower in the NP group (43% vs. 53%, p=0.05). CONCLUSIONS:
Most patients were satisfied with ED fast track, irrespective of model of care.
Patient satisfaction was greater in the group of patients using the nurse
practitioner model of care. Around half of the fast track patients would prefer
to see a general practitioner for a similar problem if available nearby.
PMID- 25113315
TI - Wildfire disasters: implications for rural nurses.
AB - BACKGROUND: As natural disasters are increasing globally, nursing's role in
responding to disasters is evolving. Disaster nursing has emerged as a specialty
that focuses on the care of groups and communities during disaster response. The
role of rural nurses in disasters is less well defined. METHODS: A review of peer
reviewed literature combined with the International Council of Nurses framework
of Disaster Nursing Competencies was conducted to understand the roles and
functions of nurses in rural areas that experience disasters. The authors'
findings from investigating the effects of four wildfires in rural Canadian
communities are also discussed. RESULTS: Six major themes derived from our
wildfire studies were generated within the context of nursing practice and are
useful in the preparation of rural nurses involved in disaster management and
recovery. This adds to the current literature which by and large has not
addressed nursing in rural catastrophes. CONCLUSION: Well-prepared and educated
rural nurses who combine theoretical knowledge with their understanding of a
rural community potentially can reduce the impact of a disaster. Other nursing
roles include mentoring nursing students in disaster preparation and assisting in
initiatives to address community recovery in the aftermath of a disaster.
PMID- 25113316
TI - Sudden onset Oculo-cardiac Reflex post-traumatic eye injury in PNG: a case study
and discussion.
AB - This case study examines the onset of traumatic OCR--Oculo-cardiac Reflex--in the
remote southern highlands of PNG. The spontaneous occurrence of OCR post-trauma
in the clinical setting leads to sudden onset bradycardia, nausea and
hypotension, resulting in cardiovascular compromise and deteriorating clinical
conditions. Initial recognition of the characteristics of OCR will prepare the
clinician to deal with the sequence of events that arise post the reflex
initiation.
PMID- 25113317
TI - Versatile Cu(I)/Pd(0) dual catalysis for the synthesis of quaternary alpha
allylated carbonyl compounds: development, mechanistic investigations and scope.
AB - We report herein a versatile cooperative dual catalysis reaction based on a
Cu(I)/Pd(0) system. Mechanistic investigation shows that every component plays a
crucial role in determining the reaction outcome. The reaction is successfully
extended to various substrates; such as alpha,beta-unsaturated ketones, malonates
and coumarins. The strategy tolerates different substitution patterns and affords
good yields for each family of substrates.
PMID- 25113318
TI - Time trends of antidepressant drug prescriptions in men versus women in a
geographically defined US population.
AB - The aim of this work was to study time trends of antidepressant drug (AD)
prescriptions in a geographically defined US population between 2005 and 2011 for
men and women separately. Using the Rochester Epidemiology Project medical
records-linkage system, we identified all Olmsted County, MN residents who
received AD outpatient prescriptions between 2005 and 2011 (7 years). We
calculated the annual age- and sex-specific prevalence over 7 years and used
generalized estimating equation models to test for time trends. The prevalence of
subjects receiving at least one AD prescription was approximately two times
higher in women than in men consistently across the 7 years of the study. The
standardized annual prevalence increased from 10.8 % in 2005 to 14.4 % in 2011
overall, from 7.0 % in 2005 to 9.9 % in 2011 for men, and from 14.4 % in 2005 to
18.6 % in 2011 for women. The absolute percent increase was greater in women (4.2
vs. 2.9 %; standardized); however, the relative percent increase was greater in
men (41.4 vs. 29.2 %; standardized). The relative percent increase was greater in
the age group 65+ years for both men and women. AD prescriptions are increasing
over time, especially in the elderly. Women receive more AD prescriptions than
men. However, the relative increase in AD prescriptions over time is greater in
men than women.
PMID- 25113319
TI - Oral contraceptive use and psychiatric disorders in a nationally representative
sample of women.
AB - The purpose of this study is to examine the association between oral
contraceptive use (any current use, duration, and type) and major depressive
disorder (MDD), generalized anxiety disorder (GAD), and panic disorder (PD) in a
nationally representative sample of women in the USA. Data were drawn from 1,105
women aged 20-39 in the National Health and Nutrition Examination Surveys from
1999 to 2004. The associations between self-reported use of oral contraceptives
in the past year and DSM-IV diagnosed and subthreshold MDD, GAD, and PD in the
past year were assessed comparing oral contraceptive users to all non-users,
former users, and former long-term users. Women using oral contraceptives had a
lower past-year prevalence of all disorders assessed, other than subthreshold
MDD. When adjusted for confounders, women using oral contraceptives in the past
year had significantly lower odds of subthreshold PD, compared to former users
(odds ratio (OR) = 0.34, 95 % CI 0.14-0.84). Effects estimates were strongest for
monophasic (versus multiphasic) oral contraceptive users. Hormonal contraceptive
use was associated with reduced risk of subthreshold PD. A potential mental
health benefit of hormonal contraceptives has substantial public health
implications; prospective longitudinal studies are needed to confirm whether
hormonal contraceptive use improves mental health.
PMID- 25113320
TI - Providing care to a child with cancer: a longitudinal study on the course,
predictors, and impact of caregiving stress during the first year after
diagnosis.
AB - OBJECTIVE: This study investigated the course, predictors, and impact of
caregiving stress on the functioning of primary caregivers of children with
cancer during the first year after a child's cancer diagnosis. METHODS: Primary
caregivers (N = 95, 100% mother, 86% response rate) of consecutive newly
diagnosed paediatric cancer patients (0-18 years) completed measures of
caregiving stress, depressive symptoms, anxiety, and self-reported health at
diagnosis, and 3, 6, and 12 months thereafter. RESULTS: Results indicated a
significant decrease in caregiving stress (especially during the first 3 months
after diagnosis). Caregiving stress was predicted by single marital status and
the ill child being the mother's only child. Multilevel analyses, controlled for
socio-demographic and medical covariates, showed that, over time, the decline in
caregiving stress was accompanied by a reduction in depressive symptoms and
anxiety. The amount of variance explained by caregiving stress was 53% for
depressive symptoms, 47% for anxiety, and 3% for self-reported health.
CONCLUSIONS: The present study suggests that caregiving stress is an important
factor in understanding parental adjustment to childhood cancer. This offers
possibilities for developing interventions aimed at preventing caregiving stress,
and strengthening mothers' confidence in their ability to provide good care.
PMID- 25113322
TI - One pot synthesis of nanoscale phase-segregated PdPt nanoarchitectures via
unusual Pt-doping induced structural reorganization of a Pd nanosheet into a PdPt
nanotent.
AB - Pt-doping of an ultrathin Pd nanosheet results in the unprecedented structural
rearrangement of a Pd nanosheet into a PdPt nanotent structure, in which a tripod
stands on a triangular nanosheet. Further growth of Pt phase on this nanotent
structure is dependent on the presence of surface-stabilizing CO molecules,
leading to the formation of two distinct nanoscale phase segregated structures
with respective structural features of a popped out Pt facet and an overgrown Pt
layer.
PMID- 25113324
TI - [Prurigo nodularis: A puzzle for more than 100 years].
PMID- 25113325
TI - [Nihil certum: historical development of the term prurigo].
AB - The term prurigo is still used to designate primary dermatoses and secondary
reaction patterns. A clear definition of the term is not available nor a clear
clinical classification of diseases categorized under the term. Furthermore,
there is no certainty about the entity it was primarily used to refer to, and
whether it should always be considered in relation to pruritus. The concept
appears already in very early medical treatises. From the very beginning, it was
used in dermatology in a non-uniform way, and was alternately accorded and denied
the status of an independent disease entity. Moreover, prurigo was subdivided
into many different forms, but their descriptions are partly very similar, so
that, for instance, it is quite difficult today to draw any conclusions about the
clinical entities the frequently used terms prurigo mitis and prurigo formicans
referred to. In contrast, the term prurigo nodularis is still commonly used. This
article traces exemplarily the use of the term prurigo in the standard medical
textbooks up to the definition of prurigo nodularis.
PMID- 25113326
TI - [Prurigo. Clinical definition and classification].
AB - BACKGROUND: There is no consistent definition of the term prurigo and a clear
classification is unavailable. OBJECTIVES: Definition of the current forms of
prurigo and a new approach to a specific classification. METHODS: Review of the
types of prurigo as presented in current textbooks and publications. RESULTS:
Pruritus is the main symptom of prurigo and shows an intensely pruritic papule or
nodule as the main efflorescence. The term prurigo is not only used for secondary
lesions, but also for primary dermatoses. The different forms of prurigo obtain
their names depending on etiology, onset and duration of lesions or the clinical
appearance. CONCLUSIONS: The term prurigo has not been used consistently. A
revision of the classification with a clear distinction between primary
dermatoses and secondary lesions seems reasonable. In secondary prurigo, a
clinical classification and the cause should be mentioned.
PMID- 25113321
TI - Comparing algorithms for automated vessel segmentation in computed tomography
scans of the lung: the VESSEL12 study.
AB - The VESSEL12 (VESsel SEgmentation in the Lung) challenge objectively compares the
performance of different algorithms to identify vessels in thoracic computed
tomography (CT) scans. Vessel segmentation is fundamental in computer aided
processing of data generated by 3D imaging modalities. As manual vessel
segmentation is prohibitively time consuming, any real world application requires
some form of automation. Several approaches exist for automated vessel
segmentation, but judging their relative merits is difficult due to a lack of
standardized evaluation. We present an annotated reference dataset containing 20
CT scans and propose nine categories to perform a comprehensive evaluation of
vessel segmentation algorithms from both academia and industry. Twenty algorithms
participated in the VESSEL12 challenge, held at International Symposium on
Biomedical Imaging (ISBI) 2012. All results have been published at the VESSEL12
website http://vessel12.grand-challenge.org. The challenge remains ongoing and
open to new participants. Our three contributions are: (1) an annotated reference
dataset available online for evaluation of new algorithms; (2) a quantitative
scoring system for objective comparison of algorithms; and (3) performance
analysis of the strengths and weaknesses of the various vessel segmentation
methods in the presence of various lung diseases.
PMID- 25113327
TI - [Pathogenesis of prurigo nodularis].
AB - BACKGROUND: Prurigo nodularis is a chronic reaction pattern associated with
severe pruritus that markedly affects the quality of life in patients.
PATHOGENESIS: The pathogenesis of prurigo nodularis is not completely clear.
Patients have an increased number of substance P and calcitonin gene-related
peptide positive nerves in the dermis. Eosinophils and mast cells are in close
vicinity to peripheral nerves and increased in numbers in the inflammatory
infiltrate in prurigo nodularis. Nerve growth factor (NGF) is increased in
lesional skin of patients and can be released by mast cells and eosinophils. In
addition, NGF modulates the functional activity of mast cells and eosinophils.
Recently, higher levels of the novel pruritic cytokine IL-31 were found in the
skin of patients with prurigo nodularis than other pruritic skin diseases.
CONCLUSION: The pathogenesis of prurigo nodularis seems to be regulated by
immunological and neuronal plasticity which will be highlighted in the current
article.
PMID- 25113328
TI - [Prurigo nodularis: its association with dermatoses and systemic disorders].
AB - BACKGROUND: Prurigo is seen in various dermatological diseases, but also in
systemic and neurological diseases. OBJECTIVES: Which diseases in dermatology,
internal medicine and neurology are linked to prurigo nodularis? MATERIAL AND
METHODS: We describe the various entities that are associated with prurigo and
discuss pathogenetic and therapeutic implications. RESULTS: In dermatology
prurigo nodularis is most frequently seen in atopic dermatitis, but also in
cutaneous lymphomas, mycobacterial skin infections and bullous diseases. Among
systemic diseases, prurigo nodularis frequently is associated with pruritus of
chronic renal or hepatic diseases. Prurigo nodularis is also seen in
hematological and metabolic diseases (such as solid tumors, lymphoma, diabetes
mellitus). The pathophysiology of prurigo is only partly understood. Treatment of
prurigo nodularis is often challenging and a multimodal approach is advisable.
CONCLUSION: Prurigo nodularis is a skin manifestation of chronic pruritus caused
by various diseases in dermatology, internal medicine and neurology. An
interdisciplinary approach should be taken for diagnosis and therapy.
PMID- 25113329
TI - [Psychosomatic aspects of prurigo nodularis].
AB - BACKGROUND/OBJECTIVES: This article gives an overview of the theoretical
background and the empirical research concerning psychosomatic aspects of prurigo
nodularis (PN). MATERIALS AND METHODS: Literature research in PubMed with the
search terms "prurigo nodularis", "nodular prurigo", "psych*"; clinical
experience and research of the authors. RESULTS: Although reviews on PN
frequently mention psychosomatic aspects, there is little empirical research
concerning the subject. Psychosomatic aspects of PN may play a role in (1) the
etiology of the chronic pruritus; (2) scratching, which leads to the typical
nodules of PN; (3) the consequences of the chronic pruritus, the scratching and
the skin lesions; (4) comorbidity. There is evidence for higher psychic
comorbidity and higher psychopathology (anxiety, depression) in PN patients than
in healthy controls, but PN patients were comparable to patients with other
pruritic dermatoses. DISCUSSION: Increased levels of psychopathological problems
and comorbidities also have been found in other dermatoses; they are not specific
for PN. Because all of the research on this topic is cross-sectional, we cannot
be sure whether these aspects are etiological factors or consequences of PN or
independent comorbidities. Nevertheless, psychosomatic aspects should be
considered in diagnosis and treatment of PN patients.
PMID- 25113330
TI - [Therapy of prurigo nodularis].
AB - Treatment of prurigo nodularis is a challenge. No specific therapies are approved
and data from clinical trials are rare. Based on our experience, case series,
randomized controlled trials as well as the S2k guideline on chronic pruritus, we
provide general principles and specific recommendations in this review.
PMID- 25113332
TI - [Reticulate necrotic lesions on lower legs].
PMID- 25113333
TI - [Acne vulgaris].
AB - Acne vulgaris is worldwide the most common skin disease. Acne is an inflammatory
disorder in whose emergence androgens, PPAR ligands, the IGF-1 signaling pathway,
regulating neuropeptides and environmental factors are probably involved. These
factors interrupt the natural cycling process in the sebaceous gland follicle and
support the transition of microcomedones to comedones and inflammatory lesions.
Proinflammatory lipids and cytokines are mediators for the development of acne
lesions. Bacterial antigens can potentate the inflammatory phenomena. Acne is
predominantly treated with combination therapy. Selecting a treatment regimen
depends on the exact classification of acne type and severity. The development of
scars is the main criterion for the choice of systemic therapy. Retinoids for
mild comedonal acne and the combination of retinoids with antibiotics and/or
benzoyl peroxide for mild to moderate papulopustular acne are the drugs of first
choice for topical treatment. The use of topical antibiotics is not recommended
any more because of the development of resistant bacterial strains. Systemic
antibiotics, in combination with topical retinoids and/or benzoyl peroxide, for
moderate papular/nodular acne and isotretinoin for severe nodular/conglobate acne
are the columns of systemic acne treatment. Systemic anti-androgens are used in
women against moderate papulopustular acne. Due to advances in the understanding
of the underlying inflammatory mechanisms in recent years the development of new
therapeutic agents with good efficacy and better side effect profile should be
expected in the future.
PMID- 25113331
TI - [Clinical features and prurigo nodularis in nephrogenic pruritus].
AB - BACKGROUND: Nephrogenic pruritus (NP) is a well-known associated symptom in
patients with chronic renal failure. The aim of the present study was to make a
detailed dermatological analysis including distribution of excoriations and their
correlation with pruritus characteristics. PATIENTS AND METHODS: Data on a total
of 17 patients with NP (14 males, mean 65.4 +/- SD 14.3 years) were subjected to
retrospective analysis. Most of the patients developed NP after start of kidney
disease; however, in 20 % of the patients, there was premonitory appearance of
the symptom 18 months (median) earlier. A majority of patients reported
neuropathic symptom qualities (burning, stinging). In 94.1 % of patients xerosis
was present; in 58.8 %, prurigo nodularis. The latter group of patients had a
longer duration of pruritus as well as up to 10 years longer duration of renal
disease than those without prurigo. RESULTS: Pruritus characteristics of NP show
a wide variance without a clear profile that is useful for clinical diagnosis. NP
can occur premonitorily, and, if of long duration and with coexistent metabolic
diseases, can develop into prurigo.
PMID- 25113334
TI - Revision of the neotropical jumping plant-louse genus Mastigimas (Hemiptera,
Psylloidea) attacking Cedrela and Toona species (Meliaceae).
AB - The small Neotropical genus Mastigimas with five described species is revised.
Three new species are added: Mastigimas colombianus sp. n. from Colombia on
Cedrela montana, M. drepanodis sp. n. from Brazil (Parana) on C. fissilis and M.
reseri sp. n. from Jamaica collected in light traps. Another two species are
recorded from Brazil and Colombia, respectively, which are not formally described
due to insufficient material. The new species are described, and illustrations
and identification keys are provided for all species. The last instar immatures
are described for five species. The phylogeny within Mastigimas is analysed, and
the biogeographic and host plant relationships are discussed.
PMID- 25113335
TI - Mature larva of Stenichnus collaris (Muller & Kunze) (Coleoptera: Staphylinidae:
Scydmaeninae).
AB - The mature larva of Stenichnus collaris is re-described on the basis of a shed
larval skin. This is the first description of an immature Stenichnus identified
by rearing to an adult beetle, and not only by collecting the larva in
association with adults, as in previously published works. New data on the life
history of St. collaris are provided, and possible serial homology of chaetotaxic
structures across body segments is discussed. The structures of immature Nearctic
St. turbatus, the only Stenichnus larva described with focus on the chaetotaxy,
are compared with those of St. collaris and possible homologies are indicated.
PMID- 25113336
TI - Morphological variation and affinities of the poorly known snake Atractus
caxiuana (Serpentes: Dipsadidae) .
AB - Atractus caxiuana was recently described based on three specimens (two males and
one female) from the Floresta Nacional de Caxiuana, municipality of Melgaco,
state of Para, in the eastern portion of the Brazilian Amazon. Apart from the
type series, no additional samples are known for the species. In this study, we
report new specimens of A. caxiuana, providing new morphological data (meristic,
morphometric, pholidosis, colour pattern, and hemipenis) and localities. We
relate the variability displayed by the characters analyzed to sexual dimorphism,
geographic variation, and ontogeny. Additionally, we provide detailed comparisons
with A. collaris and putative sister species, and propose a new species group to
accommodate this distinct and possible monophyletic assemblage.
PMID- 25113337
TI - Description of a new genus, Chileana (Hymenoptera: Chalcidoidea: Torymidae), with
four new species.
AB - Chileana Jansta & Krizkova gen. nov. and four new species, C. cyanea Jansta &
Krizkova sp. nov., C. maculata Jansta & Krizkova sp. nov., C. tricarinata Jansta
& Krizkova sp. nov. and C. penai Jansta & Krizkova sp. nov., all from Chile, are
described. The placement of this new genus within the tribe Monodontomerini is
discussed and several characters suggest a close relationship to Zaglyptonotus.
PMID- 25113338
TI - Redescription of three species of Filistatidae (Araneae) described by C.F. Roewer
from Afghanistan.
AB - Types of three filistatid species described by Roewer (1960, 1962) from
Afghanistan are redescribed and two of them transferred to other filistatid
genera. The new combinations proposed are: Zaitunia afghana (Roewer 1962) comb.
n. (ex. Filistata Latreille, 1810) and Tricalamus lindbergi (Roewer, 1962) comb.
n. (ex. Pritha Lehtinen, 1967). The taxonomic position of Pholcoides afghana
Roewer, 1960 is discussed and the species is placed in the filistatid subfamily
Prithinae Gray, 1994.
PMID- 25113339
TI - A new Philautus (Anura: Rhacophoridae) from northern Laos allied to P. abditus
Inger, Orlov & Darevsky, 1999.
AB - The small rhacophorid frog Philautus abditus is geographically restricted to
central Vietnam and adjacent Cambodia. Our fieldwork in northern Laos resulted in
the discovery of a Philautus species that very closely resembles P. abditus, but
is at least 330 km from the nearest known locality of that species. The Laos
population differs from P. abditus in mitochondrial DNA and coloration, and is
described here as a new species. Philautus nianeae sp. nov. is distinguished from
its congeners by having the combination of a hidden tympanum; no nuptial pads;
smooth skin; large black spots on the hidden surfaces of the hind limbs; light
venter with dark spotting; and a bronze iris. A second species of Philautus from
northern Laos, P. petilus, is transferred on the basis of morphology to the genus
Theloderma.
PMID- 25113340
TI - Discovery of the female of Protohermes niger Yang & Yang (Megaloptera:
Corydalidae): Sexual dimorphism in coloration of a dobsonfly revealed by
molecular evidence.
AB - In most species of Megaloptera, adult males and females have similar coloration.
In this paper, we associate the adult female of a Chinese endemic dobsonfly
species, Protohermes niger Yang & Yang, using molecular evidence from two
mitochondrial genes (16S rRNA and COI). The body and wing coloration between the
male and the female of P. niger exhibits distinct sexual dimorphism.
PMID- 25113341
TI - New contributions to the knowledge of the immatures of Stilobezzia punctulata
Lane and Stilobezzia fiebrigi Kieffer (Diptera: Ceratopogonidae).
AB - The fourth instar larva of Stilobezzia punctulata Lane is described for the first
time and the one of Stilobezzia fiebrigi Kieffer is redescribed. They are
illustrated and photomicrographed from material collected in different aquatic
environments of the province of Corrientes, Argentina. Both species show features
typical to carnivorous-predatory larva.
PMID- 25113342
TI - Neojilinga, a replacement name for Jilinga Eitschberger, Danner & Surholt, 1998
(Lepidoptera: Sphingidae).
PMID- 25113343
TI - Bees of the Colletes clypearis-group (Hymenoptera: Apoidea: Colletidae) from
China with descriptions of seven new species.
AB - Twenty-three known species of the Colletes clypearis speices group from China are
treated in this paper. C. cinerascens Morawitz 1893, C. clypearis Morawitz 1876,
C. floralis Eversmann 1852, C. impunctatus Nylander 1852, Colletes paratibeticus
Kuhlmann 2002 and Colletes sodalis (Cameron 1897) are newly recorded from China.
C. harrerioides sp. n., C. heilongtenensis sp. n., C. hirsutus sp. n., C.
inspersus sp. n., C. xizangensis sp. n., C. xuezhongi sp. n. and C. yanruae sp.
n. are described and illustrated as new species. Checklist of the known species
from China in Colletes clypearis-group with distribution, floral records, and an
illustrated key to all known males and females from China are provided. The type
specimens of the new species are deposited in the Insect Collection of Institute
of Zoology, Chinese Academy of Sciences, Beijing, China.
PMID- 25113344
TI - Taxonomic review of the family Discodorididae (Mollusca: Gastropoda:
Nudibranchia) from Brazil, with descriptions of two new species.
AB - The family Discodorididae was previously represented by 11 species in Brazil;
however, recently collected specimens from several localities in Rio de Janeiro,
in addition to the study of material previously deposited in scientific
collections, revealed the existence of 13 taxa: Diaulula greeleyi (MacFarland,
1909), Discodoris hummelincki (Ev. Marcus & Er. Marcus, 1963) comb. nov.,
Discodoris branneri MacFarland, 1909, Geitodoris pusae (Er. Marcus, 1955),
Hoplodoris hansrosaorum Dominguez, Garcia & Troncoso, 2006, Jorunna spazzola Er.
Marcus, 1955, Jorunna spongiosa sp. nov., Paradoris mulciber (Ev. Marcus, 1971),
Platydoris angustipes (Morch, 1863), Rostanga byga Er. Marcus, 1958a, Taringa
telopia Er. Marcus, 1955, Taringa iemanja sp. nov., and Thordisa diuda Er.
Marcus, 1955. Discodoris voniheringi MacFarland, 1909 was previously regarded as
nomen dubium, and this view is maintained in the present study. Three new records
for the Brazilian coast are recognized among these 13 taxa; the previous record
of Diaulula phoca (Ev. Marcus & Er. Marcus, 1967a) is rectified as Discodoris
hummelincki comb. nov., constituting the first record of this species from
Brazil; two new species, Taringa iemanja sp. nov. and Jorunna spongiosa sp. nov.,
are described in anatomical detail. The following taxa, which were formerly
considered junior synonyms of species studied in this work, have been
revalidated: Diaulula nayarita (Ortea & Llera, 1981), from the Pacific coast of
Costa Rica, which differs from Diaulula greeleyi in the length and width of
caryophyllidia; Discodoris mortenseni Ev. Marcus & Er. Marcus, 1963, from the
Caribbean, which is likely to belong to Jorunna, yet differs from Jorunna
spazzola in body size and coloration, radula appearance, and number of lamellae
in the rhinophores; Jorunna luisae Ev. Marcus, 1976, which differs from Jorunna
spazzola in the reproductive system, mainly in the size and shape of the
accessory gland; and Thordisa azmani Cervera & Garcia-Gomez, 1989, which differs
from Thordisa diuda in the presence of two accessory glands in the genital atrium
and the absence of one denticle in the external surface of the inner lateral
teeth. Finally, the specimens of Geitodoris pusae reported from the European
coast and Mediterranean Sea show differences in general coloration and in the
radula, gill, and reproductive system, thereby these specimens likely refer to
different taxa.
PMID- 25113345
TI - World synopsis of described species of the genus Platypygus Loew (Diptera:
Mythicomyiidae: Platypyginae).
AB - The taxonomy of the genus Platypygus Loew is summarized, previously described
species are reviewed based on examination of types, and a key to known species of
the genus worldwide is presented. All previously described species are diagnosed
and illustrated. The male genitalia of P. ridibundus (Costa) and female genitalia
of P. americanus Melander are described for the first time. Some characters
supporting the monophyly of the genus Platypygus are discussed and the Nearctic
Cyrtisiopsis americanus (Melander) is restored to its original combination as
Platypygus americanus. The type status of Platypygus bellus Loew, P. lativentris
Loew, P. pumilio Loew, and P. turkmenorum Paramonov is clarified and a lectotype
is selected for Platypygus kurdorum Paramonov and P. tauricus Paramonov. New
country records are given for the following species: P. bellus (Greece); P.
chrysanthemi (Israel, Jordan); P. kurdorum (Israel, Jordan, Syria); P. limatus
(Nepal, Thailand); P. pumilio (Greece, Turkmenistan); P. ridibundus (Cyprus,
Israel, Portugal), P. titanomedea (Jordan, Turkey).
PMID- 25113346
TI - Description of Culicoides paradoxalis sp. nov. from France and Portugal (Diptera:
Ceratopogonidae).
AB - A new species, Culicoides paradoxalis Ramilo and Delecolle (Diptera:
Ceratopogonidae), is described from specimens collected in France (Corsica and
southeast region) and Portugal. This species resembles Culicoides lupicaris
Downes and Kettle, and can be distinguished from this species and from Culicoides
newsteadi Austen by its wing pattern, in addition to the absence of spines on the
tarsomere 4 of female mid leg. In male, the presence of two appendices on the
sternite 9 together with the absence of sensilla coeloconica on the flagellomere
11 is also useful to distinguish these three species. Separation from other
members of the Culicoides subgenus is confirmed by the analysis of the Cytochrome
Oxidase I (COI) mitochondrial marker.
PMID- 25113347
TI - Two new species of scale mites (Acari: Pterygosomatidae) parasitizing Agama agama
(Sauria: Agamidae) from Kenya.
AB - Two new species of pterygosomatid mites Pterygosoma garissi sp. nov. and P.
fragilis sp. nov. (Acari: Pterygosomatidae) are described from the agamid lizard
Agama agama (Sauria: Agamidae) from Kenya. P. garissi sp. nov. is similar to P.
annectans Jack, 1962 but in the new species the peripheral setae are slightly
expanded apically, 3 pairs of setae are situated on the coxal fields I and and 2
pairs on II coxal fields, all pseudoanal setae are paddle-shaped with minute
spicules on the apical part, setae dFIV are absent and lTrIV present. P. fragilis
sp. nov. is most closely related to P. garissi sp. nov. but differs by the
presence of setae n on the subcapitulum, the hypostome with several denticles at
the apex, the fixed cheliceral digit bearing a spinous process, the presence of 8
9 pairs of the peripheral setae, 1-2 pairs of genital setae g, and by the
cheliceral shaft 2.1 times longer than the cheliceral base.
PMID- 25113348
TI - Two new endemic species of Ameiva (Squamata: Teiidae) from the dry forest of
northwestern Peru and additional information on Ameiva concolor Ruthven, 1924.
AB - We describe two new species of Ameiva Meyer, 1795 from the dry forest of the
Northern Peruvian Andes. The new species Ameiva nodam sp. nov. and Ameiva
aggerecusans sp. nov. share a divided frontal plate and are differentiated from
each other and from their congeners based on genetic (12S and 16S rRNA genes) and
morphological characteristics. A. nodam sp. nov. has dilated postbrachials, a
maximum known snout-vent length of 101 mm, 10 longitudinal rows of ventral
plates, 86-113 midbody granules, 25-35 lamellae under the fourth toe, and a color
pattern with 5 longitudinal yellow stripes on the dorsum. Ameiva aggerecusans sp.
nov. has not or only hardly dilated postbrachials, a maximum known snout-vent
length of 99.3 mm, 10-12 longitudinal rows of ventral plates, 73-92 midbody
granules, 31-39 lamellae under the fourth toe, and the females and juveniles of
the species normally exhibit a cream-colored vertebral stripe on a dark dorsum
ground color. We provide information on the intraspecific variation and
distribution of A. concolor. Furthermore, we provide information on the
environmental niches of the taxa and test for niche conservatism.
PMID- 25113349
TI - Polymona schellhorni sp nov., a new lymantrid moth from Jordania (Lepidoptera:
Lymantriidae).
PMID- 25113351
TI - The Australian Byrrhinae (Coleoptera: Byrrhidae) with descriptions of new genera
and species.
AB - The generic classification of the Australian Byrrhinae is revised and the
following new genera are described: Notolioon gen. n., Nothochaetes gen. n.,
Idiothrix gen. n., Akidomorychus gen. n., Brachybyrrhulus gen. n. and
Pseudomorychus gen. n. A key is provided for the genera of Australian Byrrhidae.
The following new combinations are proposed: Notolioon atronitens (Lea 1920)
comb. n., N. bryophagus (Lea 1907) comb. n., N. carissimus (Lea 1907). comb. n.,
N. dives (Lea 1907) comb. n., N. gemmatus (Lea 1920) comb. n., N. globosus
(Wilson 1921) comb. n., N. griffithi (Lea 1907) comb. n., N. maculatipes (Lea
1920) comb. n., N. multicolor (Lea 1907) comb. n., N. nodipennis (Lea 1920) comb.
n., N. simplicicornis (Lea 1907) comb. n., N. viridinitens (Lea (1920). comb. n.,
Nothochaetes fasciculatus (Lea 1920) comb. n., Idiothrix carinaticeps (Lea 1920)
comb. n., Akidomorychus comatus (Oke 1932) comb. n., A. polychromus (Lea 1920)
comb. n., A. raucus (Blackburn 1891) comb. n., A. venustus (Wilson 1921) comb.
n., Brachybyrrhulus discicollis (Lea 1920) comb. n., Pseudomorychus torrensensis
(Blackburn 1889) comb. n., P. mixtus (Lea 1907) comb. n. The following new
species are described: Notolioon cardamine sp. n., Nothochaetes howensis sp. n.
and Brachybyrrhulus malleecola sp. n.
PMID- 25113352
TI - On the endemic spider species of the genus Savigniorrhipis Wunderlich, 1992
(Araneae: Linyphiidae) in the Azores (Portugal), with description of a new
species.
AB - Savigniorrhipis topographicus new species is described from the Azores. The
synapomorphies of Savigniorrhipis are discussed along with the affinities of the
genus within the Savignia-group. Given the extremely restricted and increasingly
disturbed habitat, S. topographicus new species should be classified as
Critically Endangered and its single forest habitat at Topo (Sao Jorge Island)
should increase its current protection level to a strict nature reserve.
PMID- 25113353
TI - Review of the genus Dolichosciara Tuomikoski (Diptera, Sciaridae) from China.
AB - The genus Dolichosciara from China is reviewed and 17 species are recognized.
Among them, eight new species, D. sparsula sp. nov., D. gracilenta sp. nov., D.
oxyacantha sp. nov., D. scrobiculata sp. nov., D. tumidula sp. nov., D.
rectospinosa sp. nov., D. multisetosa sp. nov. and D. qingliangfengana sp. nov.
are described and seven species, D. ninae (Antonova, 1977), D. megumiae
(Sasakawa, 1994), D. orcina (Tuomikoski, 1960), D. semiferruginea (Menzel, 1995),
D. hippai Komarova & Vilkamaa, 2006, D. subornata (Mohrig & Menzel, 1994) and D.
ornata (Winnertz, 1867) are reported for the first time from China. In addition,
geographical distribution of 17 Chinese species are provided, as well as a key to
all these Chinese species. This study raises the number of the species of Chinese
Dolichosciara from 2 to 17.
PMID- 25113354
TI - Loricaria luciae, a new species of whiptail catfish (Siluriformes: Loricariidae)
from the Paraguay and lower Parana River basins of southeastern South America.
AB - Loricaria luciae, new species, is described from the the rio Paraguay basin of
Bolivia, Brazil, and Paraguay, south to its confluence with the rio Parana in
Argentina. It is distinguished from all congeners by the following combination of
characteristics: pectoral girdle entirely naked or with small isolated plates
near base of pectoral fin, post-ural plate at base of caudal fin large (plate
length 17.0-20.3% HL), and total lateral plates 32-33 (modally 32). The new
species occurs in a variety of habitats ranging from small, seasonally
intermittent streams with clear water to large, turbid rivers over sand and mud
substrates. It is sympatric with at least three other species of Loricaria in the
Paraguay and lower Parana drainages, including L. apeltogaster Boulenger 1895, L.
coximensis Rodriguez et al. 2012, and L. simillima Regan 1904.
PMID- 25113355
TI - A new species, Hemicrepidius (Miwacrepidius) rubriventris sp. nov. (Coleoptera,
Elateridae, Denticollinae) from Republic of Korea.
AB - The subgenus Miwacrepidius of the genus Hemicrepidius is represented by a
monotypic species, H. (M.) subcyaneus (Motschulsky 1866) from Japan, and no other
congener of the subgenus has been known until now. However, three female
specimens of a novel species belonging to this subgenus were recently collected
from the Republic of Korea. To delimitate the species boundary of the new species
compared with the monotypic species, H. (M.) subcyaneus, we attempted an
integrative taxonomy based on both morphological and DNA barcoding approaches. An
examination of the results revealed ten diagnostic characteristics and large
genetic distances, ranging from 8.40%, between these two species; therefore, we
herein describe and illustrate the new species, Hemicrepidius (Miwacrepidius)
rubriventris sp. nov., based on female types.
PMID- 25113356
TI - Notes on Citrogramma Vockeroth and Eosphaerophoria Frey (Diptera: Syrphidae).
AB - New taxonomic and distributional data on the genera Citrogramma Vockeroth, 1969
and Eosphaerophoria Frey, 1946 are presented, including descriptions of the
females of Citrogramma asombrosum Mengual, 2012, Citrogramma pennardsi Mengual,
2012 and Eosphaerophoria dentiscutellata (Keiser, 1958). Modifications to
published identification keys to accommodate the new information are provided for
both genera.
PMID- 25113357
TI - Endogean and cavernicolous Coleoptera of the Balkans. XII. New species of
Paramaurops Jeannel, 1948 (Coleoptera: Staphylinidae: Pselaphinae) from
Macedonia.
AB - The new species of the tribe Amauropini, Paramaurops vonickai n. sp. is described
from Macedonia.
PMID- 25113359
TI - Revision of the subgenus Cosmiomorpha (Cosmiomorpha)(Coleoptera: Scarabaeidae:
Cetoniinae).
AB - A taxonomic revision of the subgenus Cosmiomorpha (Cosmiomorpha) Saunders is
presented. Seven species are recognized, including four described herein, C.
fortis new species, C. nigripedis new species, C. maolanensis new species, and C.
cheni new species all from China. Cosmiomorpha baryi Bourgoin and C. squamulosa
Schurhoff are placed as junior synonyms of C. decliva Janson, and C. angulosa
Fairmaire as a synonym of C. decliva is also confirmed. Lectotypes are designated
for C. decliva Janson, C. angulosa Fairmaire, and C. squamulosa Schurhoff. Color
photographs and diagnoses of all species are provided, with comments on
intraspecific variations. A key to males is also presented. Localities of "Siao
Lou" and "Se Pin-Lou Chan" are discussed with a map.
PMID- 25113360
TI - Two interstitial species of the genus Semicytherura (Crustacea: Ostracoda) from
Japan, with notes on their microhabitats.
AB - A new interstitial ostracod, Semicytherura uzushio sp. nov., is described from
the southwest of Japan, and the details of the carapace characters of
Semicytherura mukaishimensis Okubo, 1980 are redescribed. Semicytherura uzushio
and S. mukaishimensis live interstitially in the intertidal and infralittoral
zones, respectively. They have the smallest carapaces among the known
Semicytherura species, comparable to those of other interstitial ostracods. It is
thought that most of the small species belonging to this genus have an
interstitial life style in marine sediments.
PMID- 25113361
TI - New species of Stenodactylus (Squamata: Gekkonidae) from the Sharqiyah Sands in
northeastern Oman.
AB - A new species of gecko of the genus Stenodactylus (Squamata: Gekkonidae) is
described from the dune desert of Al Sharqiyah Sands in northeastern Oman.
Stenodactylus sharqiyahensis sp. nov. is characterized morphologically by its
small size, snout shape, webbing between fingers not very extended, relatively
short limbs, and scalation. It is genetically distinct in the mitochondrial DNA
and the nuclear MC1R gene from Stenodactylus arabicus to which it has previously
been referred. The new species seems to have a restricted distribution confined
to the Sharqiyah Sands, which remain isolated from other sand deserts in Arabia.
In addition, the data presented herein confirm new locality records for
Stenodactylus arabicus in the easternmost limit of its distribution range in
western central Oman.
PMID- 25113362
TI - New species of Hypoaspis Canestrini and Coleolaelaps Berlese (Mesostigmata:
Laelapidae) associated with Polyphylla olivieri Castelnau (Coleoptera:
Scarabaeidae) in Iran .
AB - White grubs, including Polyphylla olivieri Castelnau, are among the most
economically important pests of orchard trees and other crops such as potato and
sugar beet. The larvae feed on the roots of the host plants and their adults feed
on the leaves. Several types of organisms are parasitic or phoretic on this pest,
including three species of mites from Iran. Two new species of mites, namely
Hypoaspis (Hypoaspis) surii n. sp. and Coleolaelaps massoumii n. sp. are
described here from the adults of P. olivieri in Hamedan, Iran. Hypoaspis
polyphyllae Khanjani & Ueckermann was previously described from the larva of this
species of beetle.
PMID- 25113363
TI - Description of the larva of Argia chelata Calvert, 1902 (Odonata:
Coenagrionidae).
AB - The larva of Argia chelata is described and figured. It falls into the group of
Argia larvae with a moderately prominent ligula and two palpal seta, but it
differs from its closest relatives by having labial palp with 2 setae plus one
basal setella; the length of the ligula is 30% of its maximum width; basal
tergites (1-5) lacking long, fine setae, mainly on midline; S8-10 mostly dark
brown; paraprocts with spiniform setae on basal 0.25 and 0.55 of dorsal and
ventral borders, respectively. Larvae were found in 2nd to
4th order shallow streams in cloud forest, crawling among debris, fine
sand and mud where the water flow is slow or still, close to the shoreline. The
larva is compared with A. lacrimans (Hagen), A. pima Garrison, and A. tonto
Calvert, species apparently closely related.
PMID- 25113364
TI - Cave millipedes of the United States. XIII. A new, troglobiotic species of
Austrotyla from Colorado (Diplopoda, Chordeumatida, Conotylidae).
AB - Austrotyla stephensoni n. sp., from Colorado, is described as the first
troglobiotic species of its genus, and compared to sympatric Austrotyla
coloradensis (Chamberlin 1910). A key to all Austrotyla species is provided.
PMID- 25113365
TI - The genus Rhamphothrips in India (Thysanoptera: Thripidae) with description of a
new species .
AB - Rhamphothrips bhattii sp.n. is described from India based on specimens collected
on flowers and leaves of Tabernaemontana divaricata (Apocynaceae) in the States
of West Bengal and Odisha. The pronotum of this species is longer than any other
known member of the genus. A key to the six species of Rhamphothrips recorded
from India is provided.
PMID- 25113366
TI - A new species of Mataeomera, formerly misidentified as M. obliquisigna (Hampson,
1894) from Japan (Lepidoptera, Erebidae, Boletobiinae).
AB - Mataeomera Butler, 1886, currently referred to the tribe Eublemmini in
Boletobiinae (Holloway 2011), was proposed by Butler (1886) to accommodate an
Australian species, Mataeomera dubia Butler. This genus was once regarded as a
junior synonym of Autoba Walker by Poole (1989) but resurrected by Edwards
(1996). Another related genus, Catoblemma Hampson, 1910 originally proposed for
Catoblemma sumbavensis Hampson, 1910 from Lesser Sunda was revised to include the
Australian and East and Southeast Asian species. Edwards (1996) found the
Australian species of Catoblemma and Mataeomera dubia congeneric and established
the synonymy of those two genera. Following Edwards (1996), Yoshimoto (1999)
transferred the Asian species of Catoblemma to Mataeomera. Mataeomera currently
includes 21 species (Poole 1989; Edwards 1996; Holloway 2009). Following Holloway
(2009), we note that Catoblemma appears to include several unrelated species and
is probably polyphyletic. In fact, the Indo-Himalayan and East Asian species
currently assigned to Mataeomera are distinct from the Australian congeners in
external appearance and larval feeding habits (Sohn & Ronkay 2001; Holloway
2009). As such these may merit generic status but this possibility is still under
study by the first author (JCS).
PMID- 25113367
TI - Internal oral morphology in larvae of the genus Rhinella Fitzinger, 1826
(Amphibia, Anura, Bufonidae) .
AB - From the 86 species allocated in the genus Rhinella, 25 have their tadpoles
described and only R. arenarum, R. chrysophora, R. icterica, R. ornata, R.
schneideri and R. spinulosa have aspects of the internal oral morphology
evidenced. Herein, the internal oral morphology from 12 species of Rhinella
distributed between the morphological groups of R. crucifer, R. granulosa, R.
marina and R margaritifera is described and compared. The internal oral
morphology of Rhinella is little variable in many aspects. Despite the many
similarities found between the tadpoles of Rhinella, the study showed that there
are characteristics that exhibit interspecific variation that can be used in the
taxonomy of the genus. Important features to distinguish species were: number of
infrarrostral projections; number and shape of the infralabial papillae; size,
arrangement, shape and apex of the lingual papillae; shape of the buccal floor
arena papillae; number of projections of the ventral velum; shape of the
prenarial ridge; choanae arrangement; number and apex of the postnarial papillae;
number and shape of the secondary branches on the lateral ridge papilla; buccal
roof arena papillae arrangement.
PMID- 25113368
TI - Description of the egg and immature stages of Potamobates anchicaya J. Polhemus &
D. Polhemus, 1995 (Hemiptera: Heteroptera: Gerridae) and intersexual variation in
adults.
AB - The egg and five nymphal stages, of the Neotropical species Potamobates anchicaya
are described and illustrated for the first time. Intra- and intersexual
variation in the abdominal terminalia of apterous adults is also illustrated.
Adults and nymphs were collected from three populations in southwestern Colombia.
PMID- 25113370
TI - Vulcanolepas scotiaensis sp. nov., a new deep-sea scalpelliform barnacle
(Eolepadidae: Neolepadinae) from hydrothermal vents in the Scotia Sea,
Antarctica.
AB - A new deep-sea stalked barnacle, Vulcanolepas scotiaensis sp. nov. is described
from hydrothermal vents at depths of 2400-2600 metres along segments of the East
Scotia Ridge and from 1400 metres in the Kemp Caldera. Both locations are areas
of volcanic activity that lie on the Antarctic-South American Ocean Ridge complex
near the South Sandwich Islands. This discovery confirms a wide distribution in
southern seas for Vulcanolepas, complementing the previous records from deep-sea
vents in the Lau Basin and Kermadec Ridge in the southwest Pacific, and the
Pacific Antarctic Ridge in the southeast Pacific. V. scotiaensis sp. nov., the
third described species of Vulcanolepas shows an extraordinary range in
morphology, requiring a reassessment of the original diagnosis for Vulcanolepas.
Although the morphological envelope of V. scotiaensis sp. nov. includes
representatives with a peduncle to capitulum ratio similar to that observed in
most neolepadines, the peduncle generally shows greater proportional length than
in species in any neolepadine genus except Leucolepas; it is distinguished from
other species of Vulcanolepas by a broader capitulum, much smaller imbricating
scales on the peduncle and more ornamented capitulum plates. The morphological
diversity of V. scotiaensis sp. nov. is interpreted as having arisen due to
abrupt changes in water temperature.LSID: urn:lsid:zoobank.org:act:AA2AFDA5-0B08
466A-A584-D3FDBDE9DA61.
PMID- 25113369
TI - Stictonectes abellani sp. n. (Coleoptera: Dytiscidae: Hydroporinae) from the
Iberian Peninsula, with notes on the phylogeny, ecology and distribution of the
Iberian species of the genus.
AB - Stictonectes abellani sp. n. is described from the Iberian Peninsula. On average,
the new species is larger and the colouration of the upper surface darker than in
most other species of the genus. Seemingly the species has been confounded with
others in the past, particularly S. optatus (Seidlitz, 1887). Males can be
separated from externally similar species by studying the shape of the parameres.
Additionally, the anterior margin of the clypeus is provided with a distinct rim
in both sexes, which is absent or only weakly present in other species. The
habitus and the male genitalia of the new species are illustrated, and compared
with those of S. optatus. External morphological differences from other members
of the genus are discussed. According to studies of the molecular phylogeny,
based on fragments of four mitochondrial genes, S. abellani sp. n. is clearly
separated from previously described species of Stictonectes Brinck, 1943,
apparently being relatively basal within the genus. The new species is rather
widely distributed in the south-western part of the Iberian Peninsula, inhabiting
pools in small temporary siliceous streams. We provide distributional maps for
all eight Iberian Stictonectes and estimate the potential distributional areas of
the new species and the other two endemic Iberian species S. occidentalis
Fresneda & Fery, 1990 and S. rebeccae Bilton, 2011, based on environmental niche
modelling.
PMID- 25113371
TI - Two new species of Gieysztoria (Platyhelminthes, Rhabdocoela, Dalyelliidae) from
a freshwater artificial lake in Shenzhen, China.
AB - Two new species of the "Aequales" of genus Gieysztoria were collected and
described from an artificial lake on the Shenzhen University campus. Gieysztoria
bimaculata n. sp., is distinguished based on two groups clavate pigmentations
dorsally between the pharynx and intestine, and has a sclerotic stylet comprising
a proximal girdle with 40-46 distal dagger-shape spines, thus has the maximum
number of spines within "Aequales" group. Gieysztoria guangdongensis n. sp. has a
sclerotic stylet with a proximal girdle and 18 distal blade-shaped spines.
Comparison with similar species based mainly on stylet morphology suggests that
Gieysztoria bimaculata n. sp. and Gieysztoria guangdongensis n. sp. are
apparently different from the known species of Gieysztoria in this moment. In
addition, the stability of the amount of distal spines of "Aequales" species is
briefly discussed.
PMID- 25113372
TI - Notes on the genus Libellulosoma Martin, 1906, and related genera (Odonata:
Anisoptera: Corduliidae).
AB - The holotype of Libellulosoma minuta, until now regarded as the unique specimen
of this monotypic genus and considered lost for half a century, was found again
in the dragonfly collection of the Museum National d'Histoire Naturelle in Paris.
A second specimen, also from Madagascar (probably East Madagascar) was found in
the collection Rene Martin together with the holotype. A redescription, including
the structure of the secondary copulatory apparatus, is provided. The genus
Libellulosoma is closely related to the genera Pentathemis and Aeschnosoma, and
its membership in the clade Aeschnosomata is well supported. Evidence from
biogeography, the fossil record, and phylogeny indicates that this group,
possible sister group of remaining Corduliidae s.s., was probably already present
in the Early Cretaceous.
PMID- 25113373
TI - Two new species of Microvelia Westwood, 1834 (Hemiptera: Heteroptera: Veliidae)
from Colombia, with a key to Colombian species.
AB - Only six species of Microvelia have been recorded from Colombia up to the
present, namely M. ancona, M. hinei, M. leucothea, M. longipes, M. panamensis,
and M. pulchella. Microvelia inguapi sp. n. and M. piedrancha sp. n. are herein
described and compared with similar species. An identification key to the
Colombian species of Microvelia is presented.
PMID- 25113374
TI - Chriolepis bilix, a new species of goby (Teleostei: Gobiidae) from deep waters of
the western Atlantic.
AB - A new species of seven-spined goby of the genus Chriolepis is described from four
specimens from four widely separate western Atlantic localities (Little Bahama
Bank; off southwestern Florida; Tobago Island; and northeastern Colombia) from
depths ranging from 62 to 138 m. The species is distinct from all other western
Atlantic species currently assigned to the genus Chriolepis in having a fully
scaled body, the first two dorsal-fin spines greatly elongated in both sexes,
especially so in females, and two anal-fin pterygiophores inserted anterior to
the first haemal spine. It differs from members of the similar genus Varicus in
having branched pelvic-fins rays, a longer fifth pelvic-fin ray and more numerous
meristic elements. It closely resembles Chriolepis atrimelum, known from a
similar depth at Isla del Coco in the eastern Pacific Ocean.
PMID- 25113376
TI - Reflections on eleven years with PCCP.
PMID- 25113375
TI - FAK and paxillin dynamics at focal adhesions in the protrusions of migrating
cells.
AB - Cell migration requires the fine spatiotemporal integration of many proteins that
regulate the fundamental processes that drive cell movement. Focal adhesion (FA)
dynamics is a continuous process involving coordination between FA and actin
cytoskeleton, which is essential for cell migration. We studied the
spatiotemporal relationship between the dynamics of focal adhesion kinase (FAK)
and paxillin at FAs in the protrusion of living endothelial cells. Concurrent
dual-color imaging showed that FAK was assembled at FA first, which was followed
by paxillin recruitment to the FA. By tracking and quantifying FAK and paxillin
in migrating cells, the normalized FAK/Paxillin fluorescence intensity (FI) ratio
is > 1 (~ 4 fold) at cell front, ~ 1 at cell center, and < 1 at cell rear. The
significantly higher FAK FI than paxillin FI at cell front indicates that the
assembly of FAK-FAs occurs ahead of paxillin at cell front. To determine the time
difference between the assemblies of FAK and paxillin at nascent FAs, FAs
containing both FAK and paxillin were quantified by image analysis and time
correlation. The results show that FAK assembles at the nascent FAs earlier than
paxillin in the protrusions at cell front.
PMID- 25113379
TI - Nasal MRSA colonization: impact on surgical site infection following spine
surgery.
AB - BACKGROUND: Prior studies published in the cardiothoracic, orthopedic and
gastrointestinal surgery have identified the importance of nasal (methicillin
resistant Staphylococcus aureus) MRSA screening and subsequent decolonization to
reduce MRSA surgical site infection (SSI). This is the first study to date
correlating nasal MRSA colonization with postoperative spinal MRSA SSI.
OBJECTIVE: To assess the significance of nasal MRSA colonization in the setting
of MRSA SSI. METHODS: A retrospective electronic chart review of patients from
year 2011 to June 2013 was conducted for patients with both nasal MRSA
colonization within 30 days prior to spinal surgery. Patients who tested positive
for MRSA were put on contact isolation protocol. None of these patients received
topical antibiotics for decolonization of nasal MRSA. RESULTS: A total of 519
patients were identified; 384 negative (74%), 110 MSSA-positive (21.2%), and 25
(4.8%) MRSA-positive. Culture positive surgical site infection (SSI) was
identified in 27 (5.2%) cases and was higher in MRSA-positive group than in MRSA
negative and MSSA-positive groups (12% vs. 5.73% vs. 1.82%; p=0.01). The MRSA SSI
rate was 0.96% (n=5). MRSA SSI developed in 8% of the MRSA-positive group as
compared to only in 0.61% of MRSA-negative group, with a calculated odds ratio of
14.23 (p=0.02). In the presence of SSI, nasal MRSA colonization was associated
with MRSA-positive wound culture (66.67 vs. 12.5%; p<0.0001). CONCLUSION:
Preoperative nasal MRSA colonization is associated with postoperative spinal MRSA
SSI. Preoperative screening and subsequent decolonization using topical
antibiotics may help in decreasing the incidence of MRSA SSI after spine surgery.
Nasal MRSA+ patients undergoing spinal surgery should be informed regarding their
increased risk of developing surgical site infection.
PMID- 25113380
TI - The midline suboccipital subtonsillar approach to the cerebellomedullary cistern
and its structures: anatomical considerations, surgical technique and clinical
application.
AB - OBJECTIVE: Lesions of the cerebellomedullary cistern lateral to the lower
brainstem in an area extending from the foraminae of Luschka to the foramen
magnum are rare and can be caused by various sources. There is no consensus on an
ideal surgical approach. We describe the anatomical features and the surgical
technique of the midline suboccipital subtonsillar (STA) approach to the
cerebellomedullary cistern and its pathologies. METHODS: The study was performed
on three alcohol (ETOH)-fixed specimens (6 sides), and the technique of the
approach was highlighted. The tonsillar retraction needed to view the important
structures was measured. Additionally, the records of 31 patients who underwent
the STA procedure were evaluated. We provide three clinical cases as examples.
RESULTS: Tonsillar retraction of 0.3cm (SD+/-0.1cm) exposed the PICA with its
telo-velo-tonsillar and cortical branches. Retraction of 0.4cm (SD+/-0.2cm)
exposed the spinal root of CN XI. Retraction of 0.9cm (SD+/-0.01cm) exposed the
hypoglossal canal. Retraction of 1.3cm (SD+/-0.2cm) exposed the root exit zone of
the glossopharyngeal nerve. Retraction of 1.6cm (SD+/-0.3cm) exposed the jugular
foramen (JF), and retraction of 2.4cm (SD+/-0.2cm) exposed the inner auditory
canal (IAC). In all of the selected cases, the pathology could be reached and
exposed using the STA. CONCLUSIONS: We recommend STA as a straightforward, easy
to-learn and therefore time-saving and safe procedure compared with other
standard approaches to the cerebellomedullary cistern and its pathologies.
PMID- 25113377
TI - Transcriptome sequencing and genome-wide association analyses reveal lysosomal
function and actin cytoskeleton remodeling in schizophrenia and bipolar disorder.
AB - Schizophrenia (SCZ) and bipolar disorder (BPD) are severe mental disorders with
high heritability. Clinicians have long noticed the similarities of clinic
symptoms between these disorders. In recent years, accumulating evidence
indicates some shared genetic liabilities. However, what is shared remains
elusive. In this study, we conducted whole transcriptome analysis of post-mortem
brain tissues (cingulate cortex) from SCZ, BPD and control subjects, and
identified differentially expressed genes in these disorders. We found 105 and
153 genes differentially expressed in SCZ and BPD, respectively. By comparing the
t-test scores, we found that many of the genes differentially expressed in SCZ
and BPD are concordant in their expression level (q?0.01, 53 genes; q?0.05, 213
genes; q?0.1, 885 genes). Using genome-wide association data from the Psychiatric
Genomics Consortium, we found that these differentially and concordantly
expressed genes were enriched in association signals for both SCZ (P<10(-7)) and
BPD (P=0.029). To our knowledge, this is the first time that a substantially
large number of genes show concordant expression and association for both SCZ and
BPD. Pathway analyses of these genes indicated that they are involved in the
lysosome, Fc gamma receptor-mediated phagocytosis, regulation of actin
cytoskeleton pathways, along with several cancer pathways. Functional analyses of
these genes revealed an interconnected pathway network centered on lysosomal
function and the regulation of actin cytoskeleton. These pathways and their
interacting network were principally confirmed by an independent transcriptome
sequencing data set of the hippocampus. Dysregulation of lysosomal function and
cytoskeleton remodeling has direct impacts on endocytosis, phagocytosis,
exocytosis, vesicle trafficking, neuronal maturation and migration, neurite
outgrowth and synaptic density and plasticity, and different aspects of these
processes have been implicated in SCZ and BPD.
PMID- 25113378
TI - Proneurogenic Group II mGluR antagonist improves learning and reduces anxiety in
Alzheimer Abeta oligomer mouse.
AB - Proneurogenic compounds have recently shown promise in some mouse models of
Alzheimer's pathology. Antagonists at Group II metabotropic glutamate receptors
(Group II mGluR: mGlu2, mGlu3) are reported to stimulate neurogenesis. Agonists
at those receptors trigger gamma-secretase-inhibitor-sensitive biogenesis of
Abeta42 peptides from isolated synaptic terminals, which is selectively
suppressed by antagonist pretreatment. We have assessed the therapeutic potential
of chronic pharmacological inhibition of Group II mGluR in Dutch APP (Alzheimer's
amyloid precursor protein E693Q) transgenic mice that accumulate Dutch amyloid
beta (Abeta) oligomers but never develop Abeta plaques. BCI-838 is a clinically
well-tolerated, orally bioavailable, investigational prodrug that delivers to the
brain BCI-632, the active Group II mGluR antagonist metabolite. Dutch Abeta
oligomer-forming APP transgenic mice (APP E693Q) were dosed with BCI-838 for 3
months. Chronic treatment with BCI-838 was associated with reversal of transgene
related amnestic behavior, reduction in anxiety, reduction in levels of brain
Abeta monomers and oligomers, and stimulation of hippocampal neurogenesis. Group
II mGluR inhibition may offer a unique package of relevant properties as an
Alzheimer's disease therapeutic or prophylactic by providing both attenuation of
neuropathology and stimulation of repair.
PMID- 25113381
TI - A case of contrecoup skull fracture caused by mild head injury.
PMID- 25113384
TI - Pilgrims.
PMID- 25113383
TI - Association between fasting serum glucose levels and incidence of colorectal
cancer in Korean men: the Korean Cancer Prevention Study-II.
AB - INTRODUCTION: The incidence of colorectal cancer (CRC) is steadily increasing
worldwide. Numerous studies have demonstrated that diabetes mellitus is related
to an increased risk of CRC; however, the association between impaired fasting
glucose and CRC is unclear. Therefore, we evaluated the correlation between
fasting serum glucose (FSG) levels and the incidence of CRC, which can be used to
develop novel methods for preventing CRC. METHODS: A total of 175,677 individuals
from the Korean Metabolic Syndrome Research Initiative study were enrolled
between 2004 and 2011. The incidence of CRC was assessed during a mean follow-up
of 4.7 years. Hazard ratios (HR) for CRC according to FSG levels were calculated
with the Cox proportional hazard model adjusted for age, sex, body mass index,
smoking status, alcohol consumption, and regular exercise. RESULTS: The risk of
developing CRC in subjects with high FSG was significant (HR, 1.45; 95%
confidence interval [CI], 1.10-1.90), and the risk was higher in men (HR, 1.51;
95% CI, 1.12-2.05). The HR of rectal cancer, but not colon cancer, was
significantly higher both in the total population and in men in the high FSG
group. CONCLUSIONS: The incidence of CRC positively correlated with FSG levels in
men. Rectal cancer incidence was especially correlated with high FSG in the site
specific analysis. Therefore, serum glucose levels maybe a potential marker of
colorectal cancer. Early detection and intervention for controlling elevated
glucose levels may be indicated as a way to prevent carcinogenesis.
PMID- 25113382
TI - MAG-EPA and 17,18-EpETE target cytoplasmic signalling pathways to reduce short
term airway hyperresponsiveness.
AB - This study was aimed to investigate the role of eicosapentaenoic acid
monoacylglyceride (MAG-EPA) and 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) on
the regulation of contractile reactivity and nuclear protein expression in 72-h
cultured and TNF-alpha-treated guinea pig tracheal rings. Tension measurements
performed on native tissues demonstrated that the cytochrome P-450 epoxygenase
(CYP450)-dependent EPA metabolite, 17,18-EpETE, displayed a higher potency than
MAG-EPA in inhibiting U-46619-induced tone. Calphostin C (a PKC inhibitor),
whether in association or not with MAG-EPA or 17,18-EpETE, had no further effect,
while 17,18-EpETE and Y-27632 (a Rho kinase inhibitor) yielded additive effects.
Of note, MAG-EPA and 17,18-EpETE pre-treatments normalized the contractile
responses to broncho-constrictive agents in 72-h-cultured trachea. The enhanced
expression of TNF-alpha, P-p65-nuclear factor kappaB (NF)-kappaB, c-fos and c-Jun
in 72-h-cultured tissues likely contributed to the hyperresponsiveness. beta
Escin-permeabilized preparations demonstrated that 17,18-EpETE abolished Ca(2+)
hypersensitivity, suggesting a blunting of PKC and/or Rho kinase activation.
Lastly, activation of NF-kappaB and activating protein-1 (AP-1) signalling by
exogenous TNF-alpha markedly increased the contractile response to MCh, through
an increase in 17-kDa PKC-potentiated inhibitory protein of PP1 (CPI-17)
phosphorylation and IkappaBalpha degradation. Dual incubation of 17,18-EpETE with
calphostin C or Y-27632 induced cumulative inhibitory effects on MCh responses in
TNF-alpha-incubated tracheal rings. 17,18-EpETE also reduced the detection level
of P-p65-NF-kappaB and AP-1 subunits. The present data provide evidence that MAG
EPA, through its bioactive metabolite, represents a prospective pharmacological
target in respiratory diseases.
PMID- 25113385
TI - Pseudohongiella acticola sp. nov., a novel gammaproteobacterium isolated from
seawater, and emended description of the genus Pseudohongiella.
AB - A Gram-negative, aerobic, non-spore-forming and rod-shaped or ovoid bacterial
strain able to move by a single polar flagellum, designated GBSW-5(T), was
isolated from seawater in the East Sea, South Korea. Strain GBSW-5(T) was found
to grow optimally at 30 degrees C, at pH 7.0-8.0 and in the presence of 2.0%
(w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences revealed that
strain GBSW-5(T) clustered with the type strain of Pseudohongiella spirulinae.
Strain GBSW-5(T) exhibited the highest 16S rRNA gene sequence similarity value
(96.4%) to the type strain of P. spirulinae, and of less than 91.0% sequence
similarities to the type strains of other recognized species. Strain GBSW-5(T)
was found to contain Q-8 as the predominant ubiquinone and C(18:1)omega7c and
summed feature 3 (C(16:1)omega7c and/or C(16:1)omega6c) as the major fatty acids.
The major polar lipids of strain GBSW-5(T) were identified as
phosphatidylglycerol, phosphatidylethanolamine and
phosphatidylmonomethylethanolamine. The DNA G+C content of strain GBSW-5(T) was
determined to be 59.1 mol%. The differential phenotypic properties, together with
the phylogenetic distinctiveness, revealed that strain GBSW-5(T) is separated
from P. spirulinae. On the basis of the data presented, strain GBSW-5(T) is
considered to represent a novel species of the genus Pseudohongiella, for which
the name Pseudohongiella acticola sp. nov. is proposed. The type strain is GBSW
5(T) (= KCTC 42131(T) = CECT 8627(T)). An emended description of the genus
Pseudohongiella is also given.
PMID- 25113386
TI - Granulosicoccus undariae sp. nov., a member of the family Granulosicoccaceae
isolated from a brown algae reservoir and emended description of the genus
Granulosicoccus.
AB - A Gram-stain-negative, aerobic, non-flagellated and coccoid bacterial strain, W
BA3(T), which was isolated from a brown algae reservoir in Wando of South Korea,
was characterized taxonomically. Strain W-BA3(T) was found to grow optimally at
30 degrees C, at pH 7.0-8.0 and in presence of 2.0 % (w/v) NaCl. In the
neighbour-joining phylogenetic tree based on 16S rRNA gene sequences, strain W
BA3(T) clustered with the type strains of Granulosicoccus antarcticus and
Granulosicoccus coccoides, with which it exhibited sequence similarity values of
98.4-99.3 %. Sequence similarity values of strain W-BA3(T) to the type strains of
the other recognized species were less than 90.2 %. Strain W-BA3(T) was found to
contain Q-8 as the predominant ubiquinone and summed feature 3 (C16:1 omega7c
and/or C16:1 omega6c), C18:1 omega7c and C16:0 as the major fatty acids. The
major polar lipids of strain W-BA3(T), which were identified as
phosphatidylethanolamine and phosphatidylglycerol, were similar to those of the
type strains of G. antarcticus and G. coccoides. The DNA G+C content of strain W
BA3(T) was 56.0 mol % and its mean DNA-DNA relatedness values with the type
strains of G. coccoides and G. antarcticus were 27 and 17 %, respectively.
Differential phenotypic properties, together with the phylogenetic and genetic
distinctiveness, demonstrated that strain W-BA3(T) is separated from the two
Granulosicoccus species. On the basis of the data presented, strain W-BA3(T) is
considered to represent a novel species of the genus Granulosicoccus, for which
the name Granulosicoccus undariae sp. nov. is proposed. The type strain is W
BA3(T) (=KCTC 42134(T) = NBRC 110411(T)). An emended description of the genus
Granulosicoccus is also proposed.
PMID- 25113387
TI - How 2 txt: an exploration of crafting public health messages in SMS.
AB - BACKGROUND: Health care providers are an important target audience for public
health emergency preparedness, response and recovery communications. Short
Message Service or text messaging to cell phones may be a promising supplemental
or alternative technique for reaching health care providers with time-sensitive
public health information. However, studies to date have yet to investigate the
message content and formatting requirements of providers with respect to public
health alerts and advisories or sought to understand how to meet these needs
using Short Message Service technology. METHODS: Data collection was completed
using a two-part online survey. In the first part, health care providers
identified their use of different technologies for receiving information and
provided input on the message components most important in a public health
message. In the second part, health care providers participated in an exercise in
which they shortened three public health emergency messages, ranging from 2024
2828 characters per message, to meet the 160-character limitation for text
delivery. Results were analyzed to determine associations between provider types,
age ranges, gender, access to various media (text, email, fax, social media,
etc.), and smart phone ownership. RESULTS: The following components were most
frequently selected as essential for a public health message: Topic,
Recommendation, Geographic Location, Signs & Symptoms, Population Affected, and
Link to Additional Information. There was no statistically significant
association between message component selection and provider type, age ranges, or
gender. In the message conversion exercise, we found a statistically significant
association between providers who reported receiving information by SMS and/or
smart phone ownership and including a link to additional information in the
converted message, ranging from 61% to over 72% on a per message analysis.
CONCLUSIONS: A substantive recommendation derived from this study is that public
health agencies include a link to additional website information when sending
messages in SMS format. SMS could be a useful public health tool for
communicating with health care providers but further investigation of how to
effectively use SMS and other mobile technologies is needed to inform public
health decisions regarding adoption of messaging systems utilizing these newer
technologies.
PMID- 25113389
TI - 3D Strain helps relating LV function to LV and structure in athletes.
AB - INTRODUCTION: The evaluation of cardiac contraction could benefit from a
connection with the underlying helical structure of cardiac fibers in athletes
either completely healthy or with minor common cardiopathies like Bicuspid Aortic
Valve (BAV). This study aims to exploit the potential role of 3D strain to
improve the physiological understanding of LV function and modification due to
physical activity as a comparative model. METHODS: Three age-matched groups of
young (age 20.3 +/- 5.4) individuals are prospectively enrolled: 15 normal
healthy subjects, 15 healthy athletes, and 20 athletes with bicuspid aortic valve
(BAV). All subjects underwent echocardiographic examination and both 2D and 3D
strain analysis. RESULTS: All echo parameters were within the normal range in the
three groups. Global values of end-systolic longitudinal and circumferential
strain, assesses by either 2D or 3D analysis, were not significantly different.
The 3D strain analysis was extended in terms of principal and secondary strain
(PS, SS). Global PS was very similar, global SS was significantly higher in
athletes and displays a modified time course. The comparative analysis of strain
lines pattern suggests that the enhancement of LV function is achieved by a more
synchronous recruitment of both left- and right-handed helical fibers.
CONCLUSIONS: 3D strain analysis allows a deeper physiological understanding of LV
contraction in different types of athletes. Secondary strain, only available in
3D, identifies increase of performances due to physical activity; this appears to
follow from the synergic activation of endocardial and epicardial fibers.
PMID- 25113388
TI - Nursing-sensitive indicators: a concept analysis.
AB - AIM: To report a concept analysis of nursing-sensitive indicators within the
applied context of the acute care setting. BACKGROUND: The concept of 'nursing
sensitive indicators' is valuable to elaborate nursing care performance. The
conceptual foundation, theoretical role, meaning, use and interpretation of the
concept tend to differ. The elusiveness of the concept and the ambiguity of its
attributes may have hindered research efforts to advance its application in
practice. DESIGN: Concept analysis. DATA SOURCES: Using 'clinical indicators' or
'quality of nursing care' as subject headings and incorporating keyword
combinations of 'acute care' and 'nurs*', CINAHL and MEDLINE with full text in
EBSCOhost databases were searched for English language journal articles published
between 2000-2012. Only primary research articles were selected. METHODS: A
hybrid approach was undertaken, incorporating traditional strategies as per
Walker and Avant and a conceptual matrix based on Holzemer's Outcomes Model for
Health Care Research. RESULTS: The analysis revealed two main attributes of
nursing-sensitive indicators. Structural attributes related to health service
operation included: hours of nursing care per patient day, nurse staffing.
Outcome attributes related to patient care included: the prevalence of pressure
ulcer, falls and falls with injury, nosocomial selective infection and
patient/family satisfaction with nursing care. CONCLUSION: This concept analysis
may be used as a basis to advance understandings of the theoretical structures
that underpin both research and practical application of quality dimensions of
nursing care performance.
PMID- 25113390
TI - The advances and perspectives of recombinant protein production in the silk gland
of silkworm Bombyx mori.
AB - The silk gland of silkworm Bombyx mori, is one of the most important organs that
has been fully studied and utilized so far. It contributes finest silk fibers to
humankind. The silk gland has excellent ability of synthesizing silk proteins and
is a kind tool to produce some useful recombinant proteins, which can be widely
used in the biological, biotechnical and pharmaceutical application fields. It's
a very active area to express recombinant proteins using the silk gland as a
bioreactor, and great progress has been achieved recently. This review
recapitulates the progress of producing recombinant proteins and silk-based
biomaterials in the silk gland of silkworm in addition to the construction of
expression systems. Current challenges and future trends in the production of
valuable recombinant proteins using transgenic silkworms are also discussed.
PMID- 25113391
TI - High temperature superconducting FeSe films on SrTiO3 substrates.
AB - Interface enhanced superconductivity at two dimensional limit has become one of
most intriguing research directions in condensed matter physics. Here, we report
the superconducting properties of ultra-thin FeSe films with the thickness of one
unit cell (1-UC) grown on conductive and insulating SrTiO3 (STO) substrates. For
the 1-UC FeSe on conductive STO substrate (Nb-STO), the magnetization versus
temperature (M-T) measurement shows a drop crossover around 85 K. For the FeSe
films on insulating STO substrate, systematic transport measurements were carried
out and the sheet resistance of FeSe films exhibits Arrhenius TAFF behavior with
a crossover from a single-vortex pinning region to a collective creep region.
More intriguing, sign reversal of Hall resistance with temperature is observed,
demonstrating a crossover from hole conduction to electron conduction above TC in
1-UC FeSe films.
PMID- 25113392
TI - Re: Impact of pelvicalyceal anatomy in treatment with shock wave lithotripsy and
flexible ureterorenoscopy of lower pole renal stones.
PMID- 25113396
TI - Interconvertible living radical and cationic polymerization through reversible
activation of dormant species with dual activity.
AB - The polymerization of vinyl monomers generally requires the selection of an
appropriate single intermediate, whereas in copolymerization, the selection of
the comonomer is limited by the intermediate. Herein, we propose interconvertible
dual active species that can connect comonomers through different mechanisms to
produce specific comonomer sequences in a single polymer chain. More
specifically, two different stimuli, that is, a radical initiator and a Lewis
acid, are used to activate the common dormant C-SC(S)Z group into radical and
cationic species, thereby inducing interconvertible radical and cationic
copolymerization of acrylate and vinyl ether to produce a copolymer chain that
consists of radically and cationically polymerized segments. The dual reversible
activation provides control over molecular weights and multiblock copolymers with
tunable segment lengths.
PMID- 25113394
TI - The internalizing pathway to adolescent substance use disorders: mediation by
ruminative reflection and ruminative brooding.
AB - Two subtypes of rumination were examined in relationship to substance use and
substance use disorders in adolescents. In the 8th and 9th grade, 521 adolescents
completed measures assessing depressive symptoms, conduct problems, and
reflective and brooding subtypes of rumination. In 12th grade, adolescents
reported substance use and were administered the substance use disorders modules
from the DISC. Path analyses conducted with data from 428 participants indicated
that neither depression nor rumination variables significantly affected the
presence of substance use. However, indirect effects of depression through
reflection and brooding were differentially related to risk of developing
substance use disorders, with brooding positively associated with Marijuana Use
Disorders, and reflection negatively related to both Marijuana and Alcohol Use
Disorders. Pathways did not differ by sex. These findings suggest that promoting
self-reflection may be an effective strategy to prevent and intervene with the
development of problematic substance use.
PMID- 25113395
TI - Newcomers in a hazardous environment: a qualitative inquiry into sex worker
vulnerability to HIV in Bali, Indonesia.
AB - BACKGROUND: Women new to sex work and those with a greater degree of mobility
have higher risk of HIV infection. Using social capital as a theoretical
framework, we argue that better understanding of the interactions of micro-level
structural factors can be valuable in reshaping and restructuring health
promotion programmes in Bali to be more responsive to the concerns and needs of
newcomer and mobile female sex workers (FSWs). METHODS: We conducted interviews
with 11 newcomer FSWs (worked < six months), 9 mobile FSWs (experienced but
worked at the current brothel < six months), and 14 senior FSWs (experienced and
worked at current brothel > six months). The interviews explored women's
experience of sex work including how and why they came to sex work, relationships
with other FSWs and their HIV prevention practices. RESULTS: A thematic framework
analysis revealed newcomer FSWs faced multiple levels of vulnerability that
contributed to increased HIV risk. First, a lack of knowledge and self-efficacy
about HIV prevention practices was related to their younger age and low exposure
to sexual education. Second, on entering sex work, they experienced intensely
competitive working environments fuelled by economic competition. This
competition reduced opportunities for positive social networks and social
learning about HIV prevention. Finally, the lack of social networks and social
capital between FSWs undermined peer trust and solidarity, both of which are
essential to promote consistent condom use. For example, newcomer FSWs did not
trust that if they refused to have sex without a condom, their peers would also
refuse; this increased their likelihood of accepting unprotected sex, thereby
increasing HIV risk. CONCLUSIONS: Public health and social welfare interventions
and programmes need to build social networks, social support and solidarity
within FSW communities, and provide health education and HIV prevention resources
much earlier in women's sex work careers.
PMID- 25113398
TI - Prognostic significance of perineural invasion in stage IIA colon cancer.
AB - BACKGROUND: Perineural invasion (PNI) may influence the prognosis of colon
cancer, but little is known about its predictive value. The aim of this study was
to reveal the role of PNI in predicting prognosis after curative resection of
colon cancer, especially T3N0. METHODS: Two hundred and fifty-five patients who
underwent curative resection for colon cancer at Samsung Medical Center and were
later diagnosed with stage T3N0 by a pathological report between November 2004
and December 2007 were retrospectively recruited into the study. RESULTS: Among
the 255 patients, 156 were male and 99 were female. The mean age was 61 years
(range, 25 to 88 years). The most common tumour location was the sigmoid colon
(93 patients, 36.5%). The median follow-up period was 61 months (range, 1 to 98
months). PNI was detected in 18 patients (7.1%). Adjuvant chemotherapy was
performed in 205 patients (80.4%). The 5-year disease-free survival rate was
greater for patients with PNI negative tumours compared with those with PNI
positive tumours (92.0% versus 76.0%, P = 0.025). Adjuvant chemotherapy was not
associated with significant differences in survival rate (94.8% versus 96.9%, P =
0.625). On multivariate analysis, PNI was an independent prognostic factor for
disease-free and overall survival (P = 0.046, hazard ratio (HR) = 3.113, 95%
confidence interval (CI) = 1.020-9.505 and P = 0.019, HR = 9.395, 95% CI = 1.453
60.755 respectively). CONCLUSIONS: PNI is the only significant prognostic factor
affecting disease-free and overall survival in patients with T3N0 colon cancer.
PMID- 25113399
TI - Low cord blood Foxp3/CD3gamma mRNA ratios: a marker of increased risk for allergy
development.
AB - BACKGROUND: Data from birth cohort studies suggest that increased cord blood
total IgE and reduced cord blood regulatory T cells increase the risk of
developing allergic sensitization and atopic dermatitis. OBJECTIVE: We here
addressed whether serum total IgE and hen's egg-specific IgE levels at birth and
at age 1 year differed between healthy and allergic children in a Belgian birth
cohort (FONIA). We furthermore studied whether these parameters as well as cord
blood Foxp3/CD3gamma mRNA levels might predict the allergic outcome. METHODS AND
RESULTS: Children (n = 84) were clinically assessed at the ages of 6, 12, 18, and
24 months and at 6 years. Cord blood total IgE levels above 0.35 kU/L predicted
early (i.e. before or at the age of 2 years) allergy development. Presence of
serum IgE antibodies to hen's egg (cut-off 0.05 Ua/mL) at the age of 1 year was
associated with early as well as late (i.e. between the age of 2 and 6 years)
allergy development. Cord blood Foxp3/CD3gamma mRNA ratios were significantly
lower in early allergic children and levels below 0.32 predicted the allergic
outcome. CONCLUSIONS AND CLINICAL RELEVANCE: Low cord blood Foxp3/CD3gamma mRNA
ratios are highly predictive for early allergy development, whereas specific IgE
levels to hen's egg white above 0.05 Ua/mL at age 1 year predict allergy
development in general.
PMID- 25113397
TI - Kindergarteners' self-reported social inhibition and observed social reticence:
moderation by adult-reported social inhibition and social anxiety disorder
symptoms.
AB - Prevention of later anxiety problems would best be accomplished by identifying at
risk children early in development. For example, children who develop Social
Anxiety Disorder (SAD) may show social withdrawal in the form of social
inhibition (i.e., shyness with unfamiliar adults and peers) at school entry.
Although the use of children's perceptions of their own social inhibition would
provide insight into early risk, the utility of young children's self-reports
remains unclear. The current study examined whether children deemed more extreme
on social inhibition or social anxiety by adult report provided self-report of
social inhibition that related to observed social reticence in the laboratory.
Participants included 85 kindergarten children (36 female, 49 male), their
parents, and their teachers. Moderation analyses revealed that children's self
reported social inhibition related significantly to observed social reticence
under the conditions of high parent-reported social inhibition, high teacher
reported social inhibition, and high SAD symptoms. These results suggest that the
most inhibited children are aware of their behavior and can report it in a
meaningfully way as young as kindergarten age.
PMID- 25113400
TI - Involvement of the NF-kB/p50/Bcl-3 complex in response to antiangiogenic therapy
in a mouse model of metastatic renal cell carcinoma.
AB - Renal cell carcinoma (RCC) represents approximately 2-3% of human malignancies.
Nuclear transcription factor kB (NF-kB) is composed of a family of transcription
factors that have been associated with the development and progression of RCC.
Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic
activity. In this study, we evaluated the expression of NF-kB in metastatic tumor
cells from animals treated with ES. Balb/c-bearing Renca-EGFP cells were treated
with NIH/3T3-LendSN or NIH/3T3-LXSN cells as a control. At the end of the in vivo
experiment, plasma Renca-EGFP-sorted cells and tissue lung samples were
collected. A real-time PCR array for NF-kappaB target genes revealed that ES
therapy led to down regulation of Bcl-3 (P<0.031), NF-kB1 (P<0.001) and c-Rel
(P<0.004) in the ES-treated group. Using an electrophoretic mobility shift assay
(EMSA), we observed a reduction in NF-kB binding activity in ES-treated Renca-EGP
cells. Furthermore, a supershift assay showed a clear shift of the NF-kB DNA band
in samples incubated with a p50 antibody. By immunohistochemistry analysis, ES
treatment resulted in a significant reduction in expression of p50. (ES vs.
control P<0.05). The immunoprecipitation experiments confirmed the presence of a
p50/Bcl-3 complex in nuclear extracts from cells of metastatic lung tissues. Our
findings indicate that p50 and Bcl-3 plays a regulatory role in gene
transcription in RCC.
PMID- 25113401
TI - Effective utilization of flue gases in raceway reactor with event-based pH
control for microalgae culture.
AB - This work addresses effective utilization of flue gases through the proper pH
control in raceway reactors. The pH control problem has been addressed with an
event-based control approach using a Generalized Predictive Controller (GPC) with
actuator deadband. Applying this control strategy it is possible to reduce the
control effort, and at the same time saving control resources. In the pH process
case, the event-based controller with actuator deadband can be tuned to supply
only necessary amount of CO2 to keep the pH close to its optimal value. On the
other hand, the evaluated control algorithm significantly improves the pH control
accuracy, what has a direct influence on biomass production. In order to test the
performance of the event-based GPC controller, several experiments have been
performed on a real raceway reactor. Additionally, several control performance
indexes have been used to compare the analyzed technique with commonly used
on/off controller.
PMID- 25113403
TI - Instrumentation for capillary electrophoresis and microchip electrophoresis.
PMID- 25113393
TI - The hidden history of the snowshoe hare, Lepus americanus: extensive
mitochondrial DNA introgression inferred from multilocus genetic variation.
AB - Hybridization drives the evolutionary trajectory of many species or local
populations, and assessing the geographic extent and genetic impact of
interspecific gene flow may provide invaluable clues to understand population
divergence or the adaptive relevance of admixture. In North America, hares (Lepus
spp.) are key species for ecosystem dynamics and their evolutionary history may
have been affected by hybridization. Here we reconstructed the speciation history
of the three most widespread hares in North America - the snowshoe hare (Lepus
americanus), the white-tailed jackrabbit (L. townsendii) and the black-tailed
jackrabbit (L. californicus) - by analysing sequence variation at eight nuclear
markers and one mitochondrial DNA (mtDNA) locus (6240 bp; 94 specimens). A
multilocus-multispecies coalescent-based phylogeny suggests that L. americanus
diverged ~2.7 Ma and that L. californicus and L. townsendii split more recently
(~1.2 Ma). Within L. americanus, a deep history of cryptic divergence (~2.0 Ma)
was inferred, which coincides with major speciation events in other North
American species. While the isolation-with-migration model suggested that nuclear
gene flow was generally rare or absent among species or major genetic groups,
coalescent simulations of mtDNA divergence revealed historical mtDNA
introgression from L. californicus into the Pacific Northwest populations of L.
americanus. This finding marks a history of past reticulation between these
species, which may have affected other parts of the genome and influence the
adaptive potential of hares during climate change.
PMID- 25113402
TI - Enhanced removal of COD and color from landfill leachate in a sequential
bioreactor.
AB - In the present study, a sequential treatment process was carried out using a
fungal sp. (Phanerochaete sp.) followed by a bacterial sp. (Pseudomonas sp.) for
the degradation and detoxification of contaminants in landfill leachate. The
process was optimized using Box-Behnken design (BBD) and response surface
methodology (RSM) for three variables (C source, N source and duration), while
monitoring two responses (% COD and color removal). After treatment in a
bioreactor under optimized conditions, enhanced removal of COD (76.9%) and color
(45.4%) was observed. Further, GC-MS analysis of metabolites detected at
different stages of treatment showed formation of degradation products of lignin
and polycyclic aromatic compounds. Treatment efficiency was finally evaluated by
the alkaline comet assay in HepG2 human hepato-carcinoma cells. The results
indicated no statistically significant DNA damage at the end of the treatment,
making the effluent suitable to be discharged conforming to the safety standards.
PMID- 25113408
TI - Clinical inertia in individualising care for diabetes: is there time to do more
in type 2 diabetes?
AB - Clinical inertia is defined as the failure to establish appropriate targets and
escalate treatment to achieve treatment goals. It accounts for a significant
proportion of failure to achieve targets in the management of diabetes and
contributes to up to 200,000 adverse diabetes- related outcomes per year. Despite
a growing awareness of the phenomenon, and newer, better-tolerated agents for the
control of diabetes, there has been little improvement over the last decade in
the prevalence of clinical inertia. Although common-place in clinical practice,
clinical inertia does not appear to affect clinical trials. There are lessons
that may be translated from these randomised controlled trials to clinical
practice, which that may improve the care for those with diabetes. Key amongst
these interventions are good education, clear treatment strategy and more time
for interaction between physician and patients, all of which appears to reduce
clinical inertia as evidenced by the "placebo effect" of clinical trials. We plan
to review here, the lessons that can be learnt from clinical trials and how these
may translate to better care for people with diabetes.
PMID- 25113407
TI - Fast and versatile fabrication of PMMA microchip electrophoretic devices by laser
engraving.
AB - This paper describes the effects of different modes and engraving parameters on
the dimensions of microfluidic structures produced in PMMA using laser engraving.
The engraving modes included raster and vector, while the explored engraving
parameters included power, speed, frequency, resolution, line-width, and number
of passes. Under the optimum conditions, the technique was applied to produce
channels suitable for CE separations. Taking advantage of the possibility to cut
through the substrates, the laser was also used to define solution reservoirs
(buffer, sample, and waste) and a PDMS-based decoupler. The final device was used
to perform the analysis of a model mixture of phenolic compounds within 200 s
with baseline resolution.
PMID- 25113410
TI - Alternative methods for toxicity assessments in fish: comparison of the fish
embryo toxicity and the larval growth and survival tests in zebrafish and fathead
minnows.
AB - An increased demand for chemical toxicity evaluations has resulted in the need
for alternative testing strategies that address animal welfare concerns. The fish
embryo toxicity (FET) test developed for zebrafish (Danio rerio) is one such
alternative, and the application of the FET test to other species such as the
fathead minnow (Pimephales promelas) has been proposed. In the present study, the
performances of the FET test and the larval growth and survival (LGS; a standard
toxicity testing method) test in zebrafish and fathead minnows were evaluated.
This required that testing methods for the fathead minnow FET and zebrafish LGS
tests be harmonized with existing test methods and that the performance of these
testing strategies be evaluated by comparing the median lethal concentrations of
2 reference toxicants, 3,4-dicholoraniline and ammonia, obtained via each of the
test types. The results showed that procedures for the zebrafish FET test can be
adapted and applied to the fathead minnow. Differences in test sensitivity were
observed for 3,4-dicholoraniline but not ammonia; therefore, conclusions
regarding which test types offer the least or most sensitivity could not be made.
Overall, these results show that the fathead minnow FET test has potential as an
alternative toxicity testing strategy and that further analysis with other
toxicants is warranted in an effort to better characterize the sensitivity and
feasibility of this testing strategy.
PMID- 25113409
TI - Comparison of magnetic resonance imaging sequences for depicting the subthalamic
nucleus for deep brain stimulation.
AB - Electrodes are surgically implanted into the subthalamic nucleus (STN) of
Parkinson's disease patients to provide deep brain stimulation. For ensuring
correct positioning, the anatomic location of the STN must be determined
preoperatively. Magnetic resonance imaging has been used for pinpointing the
location of the STN. To identify the optimal imaging sequence for identifying the
STN, we compared images produced with T2 star-weighted angiography (SWAN),
gradient echo T2*-weighted imaging, and fast spin echo T2-weighted imaging in 6
healthy volunteers. Our comparison involved measurement of the contrast-to-noise
ratio (CNR) for the STN and substantia nigra and a radiologist's interpretations
of the images. Of the sequences examined, the CNR and qualitative scores were
significantly higher on SWAN images than on other images (p < 0.01) for STN
visualization. Kappa value (0.74) on SWAN images was the highest in three
sequences for visualizing the STN. SWAN is the sequence best suited for
identifying the STN at the present time.
PMID- 25113411
TI - Term breech deliveries in the Netherlands: did the increased cesarean rate
affect neonatal outcome? A population-based cohort study.
AB - OBJECTIVE: The aim of this study was to evaluate the effect of the increased
cesarean rate for term breech presentation on neonatal outcome. We also
investigated whether the clinical case selection for vaginal delivery applied by
Dutch obstetricians led to an optimization of neonatal outcome, or whether there
is still room for improvement in terms of perinatal outcome. DESIGN:
Retrospective cohort. SETTING: The Netherlands. POPULATION: Singleton term breech
deliveries from 37+0 to 41+6 weeks, excluding fetuses with congenital
malformations or antenatal death. METHOD: We used data from the Dutch national
perinatal registry from 1999 up to 2007. MAIN OUTCOME MEASURES: Perinatal
mortality and morbidity. RESULTS: We studied 58,320 women with a term breech
delivery. There was an increase in the elective cesarean rate (from 24 to 60%).
As a consequence, overall perinatal mortality decreased [1.3 0/00 vs. 0.7
0/00;odds ratio 0.51 (95% confidence interval 0.28-0.93)], whereas it remained
stable in the planned vaginal birth group [1.7 0/00 vs. 1.6 0/00; odds ratio
0.96(95% confidence interval 0.52-1.76)]. The number of cesareans done to prevent
one perinatal death was 338. CONCLUSIONS: Adjustment of the national guidelines
after publication of the Term Breech Trial resulted in a shift towards elective
cesarean and a decrease of perinatal mortality and morbidity among women
delivering a child in breech at term. Still, 40% of these women attempt vaginal
birth. The relative safety of an elective cesarean should be weighed against the
consequences of a scarred uterus in future pregnancies.
PMID- 25113412
TI - Giant enhancement of ferroelectric retention in BiFeO3 mixed-phase boundary.
AB - A large enhancement of nanodomain retention is shown in the mixed-phase region of
a strained BiFeO3 epitaxial film. The superior ferroelectric retention is
attributed to a lower elastic-energy density at the phase boundaries, which act
as periodic pinning centers for the domain wall motion. This study delivers a new
pathway of incorporating an elastic-energy term to assist ferroelectric
retention.
PMID- 25113414
TI - Long-term sevelamer treatment lowers serum fibroblast growth factor 23
accompanied with increasing serum Klotho levels in chronic haemodialysis
patients.
AB - AIMS: Fibroblast growth factor 23 (FGF23) and Klotho are associated with vascular
calcification and cardiovascular disease in dialysis patients. Sevelamer has been
shown to reduce progression of vascular calcification. This study aimed to
determine the long-term effect of sevelamer treatment on serum FGF23 and Klotho
levels in chronic haemodialysis (HD) patients. METHODS: In the post-hoc analysis,
we measured serum FGF23, Klotho and other biochemical factors (Ca, P, i-PTH,
hsCRP, LDL-C) in 50 haemodialysis patients, who completed a 48-week, open-Label,
controlled randomized parallel-group study. Twenty-three patients received
sevelamer and 27 patients received calcium carbonate. RESULTS: After 48-week
sevelamer treatment, there were significant changes with lower LDL-C (from 2.82
+/- 0.78 to 1.65 +/- 0.53 mmol/L, P = 0.000), lower FGF23 (from 2465.97 (2568.88)
to 795.61 (1098.39), P = 0.000) and higher s-Klotho levels (from 189.35 (161.88)
to 252.94 (517.80) pg/mL, P = 0.000). In calcium carbonate group, there were no
significant changes of LDL-C and FGF23, but with a borderline significant
increase of s-Klotho level (from 142.34 (265.24) to 188.57 (252.38) pg/mL, P =
0.054). Multivariate analysis showed that FGF23 decrement was associated with
sevelamer treatment (beta = -0.277, P = 0.005), change of serum phosphate (beta =
0.609, P = 0.000) and calcium levels (beta = 0.635, P = 0.000). The increase of
serum Klotho was associated with the decrease of serum phosphate (beta = 0.490, P
= 0.019). CONCLUSION: Maintenance HD patients had lower serum FGF23 levels,
accompanied with significantly increased serum Klotho levels, after 48-week
sevelamer treatment. The FGF23 decrement was associated with sevelamer use, the
change of serum phosphate and calcium levels. The serum Klotho increment was
proportional to the phosphate-lowering power of the binders.
PMID- 25113413
TI - Stress response signaling and virulence: insights from entomopathogenic fungi.
AB - The Ascomycete fungal insect pathogens, Beauveria and Metarhizium spp. have
emerged as model systems with which to probe diverse aspects of fungal growth,
stress response, and pathogenesis. Due to the availability of genomic resources
and the development of robust methods for genetic manipulation, the last 5 years
have witnessed a rapid increase in the molecular characterization of genes and
their pathways involved in stress response and signal transduction in these
fungi. These studies have been performed mainly via characterization of gene
deletion/knockout mutants and have included the targeting of general proteins
involved in stress response and/or virulence, e.g. catalases, superoxide
dismutases, and osmolyte balance maintenance enzymes, membrane proteins and
signaling pathways including GPI anchored proteins and G-protein coupled membrane
receptors, MAPK pathways, e.g. (i) the pheromone/nutrient sensing, Fus3/Kss1,
(ii) the cell wall integrity, Mpk1, and (iii) the high osmolarity, Hog1, the
PKA/adenyl cyclase pathway, and various downstream transcription factors, e.g.
Msn2, CreA and Pac1. Here, we will discuss current research that strongly
suggests extensive underlying contributions of these biochemical and signaling
pathways to both abiotic stress response and virulence.
PMID- 25113415
TI - Change in health status in long-term conditions over a one year period: a cohort
survey using patient-reported outcome measures.
AB - BACKGROUND: Enhancing quality of life for people with long-term conditions by
monitoring patient-reported outcome measure scores is a key domain of health care
policy. This study investigated the responsiveness of patient-reported outcome
measures for long-term conditions. METHODS: A cohort survey was conducted in 33
primary care practices and 4485 patients (1334 asthma, 567 chronic obstructive
pulmonary disease, 1121 diabetes, 525 epilepsy, 520 heart failure and 418 stroke)
were sent a baseline survey containing a generic (EQ-5D) and a disease-specific
measure. Baseline respondents were sent a follow-up after 1 year. Differences in
scores for each long-term condition were assessed by paired t-tests. The
relationship between scores and self-reported 'change in health' was assessed by
analysis of variance. RESULTS: The baseline achieved a 38.4% response rate and
the follow-up 71.5%. The only significant difference for the EQ-5D was found for
the Visual Analogue Scale in heart failure between baseline and follow-up, and
for change in health. Significant differences between baseline and follow-up
scores were found on the disease-specific measures for 1 asthma dimension and 1
stroke dimension. No significant differences were found for other conditions.
Significant differences between self-reported change in health and the disease
specific measures were found for 4 asthma dimensions and 2 stroke dimensions.
CONCLUSIONS: Few significant differences were found between the baseline and
follow up or between 'change in health' and PROMs scores. This could be explained
by the time frame of one year being too short for change to occur or by the PROMs
not being responsive enough to change in a primary care sample. The latter is
unlikely as the PROMs were in part chosen for their responsiveness to change. The
baseline response rates may mean that the sample is not representative, and
stable patients may have been more likely to participate. If PROMs are to be used
routinely to monitor outcomes in LTCs, further research is needed to maximize
response rates, to ensure that the PROMs used are reliable, valid and sensitive
enough to detect change and that the time frame for data collection is
appropriate.
PMID- 25113416
TI - Study on the immune response to recombinant Hsp70 protein from Megalobrama
amblycephala.
AB - The expression of heat shock protein 70 (Hsp70) is induced in response to many
factors including high temperature, infection, metal pollutants and toxic
chemicals. In this study, Megalobrama amblycephala HSP70 promoter was cloned, and
characteristic heat shock elements (HSEs) were identified in the promoter region.
The recombinant M. amblycephala Hsp70 protein (rMaHsp70) was expressed and
purified from Escherichia coli BL21 (DE3). To evaluate in vivo immune response of
rMaHsp70, we administered intraperitoneal (IP) injection, and demonstrated that
rMaHsp70 stimulated M. amblycephala immune activity by inducing the expression of
HSP70, HIF-1alpha, HSC70, CXCR4b, TNF-alpha and IL-1beta mRNAs in liver,
headkidney, spleen and gill, as well as SOD, glutathione, lysozyme and interferon
alpha proteins in serum and liver. The effect of rMaHsp70 as adjuvant against
Aeromonas hydrophila was assessed by injecting a mixed vaccine of rMaHsp70 and A.
hydrophila (A. hydrophila/Hsp70) into M. amblycephala, and the relative percent
survival (RPS) in the A. hydrophila/Hsp70 group was 75% compared to 50% in the A.
hydrophila/PBS group. Furthermore, rMaHsp70 also promoted the proliferation and
suppressed apoptosis in M. amblycephala fin cells (MAF) in a dose-dependent
manner. Taken together, these results suggest that rMaHsp70 can induce organic
immune response and improve environmental tolerance.
PMID- 25113417
TI - Both habitual short sleepers and long sleepers are at greater risk of obesity: a
population-based 10-year follow-up in women.
AB - OBJECTIVE: To assess how change in sleep duration is related to subsequent
obesity. METHODS: In this 10-year follow-up, 4903 non-pregnant participants
answered a questionnaire on sleeping habits, obesity, and lifestyle factors
(questions identical to baseline questionnaire). Habitual normal sleepers were
defined as sleeping 6-9 h/night at both baseline and follow-up, whereas women
sleeping <6 h/night or >=9 h/night at both occasions were defined as habitual
short sleepers and habitual long sleepers, respectively. Logistic regression was
used to analyze associations between changes in sleep duration, general obesity
(body mass index >=30 kg/m(2)), weight gain (>=10 kg) and also, central obesity
(waist circumference >=88 cm), and increase in waist circumference (>=10 cm) at
follow-up. RESULTS: Among younger women (aged <40 years) both habitual short
sleepers and habitual long sleepers had a higher prevalence of general (short:
31.3%, P < 0.0001; long: 38.1%, P = 0.01) and central obesity (short: 60.5%, P =
0.01; long: 82.4%, P = 0.01) compared with habitual normal sleepers (general
obesity: 8.9%; central obesity: 35.9%) at follow-up. Younger women who were short
sleepers at baseline but normal sleepers at the follow-up had a higher prevalence
of both general (19.3%, P = 0.01) and central obesity (45.4%, P = 0.07) compared
with habitual normal sleepers at follow-up. In adjusted analyses, both habitual
short [adjusted odds ratio (aOR), 6.78; 95% confidence interval (CI), 2.71-17.0]
and long (aOR, 4.64; 95% CI, 1.09-19.8) sleep durations were risk factors for
general obesity in younger women. In younger women habitual long sleep duration
was a risk factor also for central obesity (aOR, 6.05; 95% CI, 1.19-30.7) whereas
habitual short sleep duration was not (aOR, 1.93; 95% CI, 0.87-4.81). Similar
results were seen also for weight gain and increased waist circumference as
dependent variables. In addition, decreased sleep duration from normal to short
duration was a risk factor for both weight gain (aOR, 1.85; 95% CI, 1.14-3.02)
and increased waist circumference (aOR, 1.84; 95% CI, 1.20-2.81). There were no
associations between changes in sleep duration and any of the measures of obesity
at the follow-up in women aged >40 years at baseline. CONCLUSION: In younger
women, both habitual short and long sleep duration was a risk factor for obesity,
whereas no such relationship was seen in older women.
PMID- 25113418
TI - Quantifying the influence of safe road systems and legal licensing age on road
mortality among young adolescents: steps towards system thinking.
AB - Based on existing literature, a system thinking approach was used to set up a
conceptual model on the interrelationships among the components influencing
adolescent road mortality, distinguishing between components at the individual
level and at the system level. At the individual level the role of risk behaviour
(sometimes deliberate and sometimes from inexperience or other non-deliberate
causes) in adolescent road mortality is well documented. However, little is known
about the extent to which the 'road system' itself may also have an impact on
younger adolescents' road mortality. This, by providing a safe or unsafe road
environment for all road users (System-induced exposure) and by allowing access
to high-risk vehicles at a young or older age through the legal licensing age.
This study seeks to explore these relationships by analysing the extent to which
the road mortality of 10 to 17 year olds in various jurisdictions can be
predicted from the System-induced Exposure (SiE) in a jurisdiction and from its
legal licensing age to drive motor vehicles. SiE was operationalized as the
number of road fatalities per 10(5) inhabitants/all ages together, but excluding
the 10 to 17 year olds. Data on road fatalities during the years 2001 through
2008 were obtained from the OECD International Road Traffic Accident Database
(IRTAD) and from the USA NHTSA's Fatality Analysis Reporting System (FARS)
database for 29 early and 10 late licensing jurisdictions. Linear mixed models
were fitted with annual 'Adolescent road mortality per capita' for 2001 through
2008 as the dependent variable, and time-dependent 'SiE' and time-independent
'Licensing system' as predictor variables. To control for different levels of
motorisation, the time-dependent variable 'Annual per capita vehicle distance
travelled' was used as a covariate. Licensing system of a jurisdiction was
entered as a categorical predictor variable with late licensing countries as a
baseline group. The study found support for the protective effects of SiE on
adolescent safety. If SiE increased by one unit, the mortality rate of 10 to 17
year olds increased by 0.487 units. No support was found for a protective effect
of late licensing for this age group. Thus, compared to young adolescents who are
allowed to drive motor vehicles in early licensing jurisdictions, late licensing
does not provide extra protection for pre-license adolescents. This finding is
probably the result of the high risks associated with alternative transport
modes, such as moped riding and bicycling. Also, the fact that the study only
included risks to young adolescents themselves and did not include the risks they
might pose to other road users and passengers may have contributed to this
finding, because such risks are greater when driving a motor vehicle than riding
a moped or a bicycle. Therefore, to advance our understanding of the impact of
licensing systems, more study is needed into the benefits of early or late
licensing, thereby considering these wider effects as well.
PMID- 25113419
TI - [Alcohol consumption in patients with psychiatric disorders: assessment and
treatment].
AB - Alcohol consumption in France exceeds the European average (12.7L of pure
alcohol/habitant/year in 2009 for an average of 12.5 L). This consumption has a
major professional, social and health impact on the individuals and their
families. The cost of such, estimated in Europe to be of 155.8 billion Euros in
2010, is the highest among the central nervous system diseases in Europe, far
higher than that of depression or dementia. Patients suffering from psychiatric
disorders are more frequently affected by problems related to alcohol use than
the general population. They are also more vulnerable to the immediate and
subsequent consequences of their consumption. The alcohol related disorders that
are often accompanied by risk taking and other addictive behaviour require a
global assessment of the addiction, with and without substance, and of the
complications. These have a strong impact on risk taking, compliance with care,
and the morbidity of somatic and psychiatric disorders, as well as access to
optimal care and the life span of patients suffering from psychiatric disorders.
The development of addictology care, with integrative treatment programs, is
recommended in response to these public health issues. Nevertheless, specific
addictology practices and partners with addictology care structures are still
scarcely developed in psychiatry. Firstly, it would be necessary to set up such
integrated treatments through the systematisation of an "addictology" checkup on
admission, a global assessment of addictive behaviour and cognitive disorders,
using pragmatic tools that are user-friendly for the care teams, maintain the
reduction in risk taking, and apply prescriptions for addiction to psychotropic
treatments, in liaison with the referring general practitioner. As early as
possible, accompanied by specific training in addictology for the psychiatrists
and the mental health nursing teams, such care could be enhanced by the
development of liaison and advanced psychiatric consultation teams, specialised
in addictology, together with the installation of a addictology care network in
supplementary psychiatry of levels 1, 2 and 3 in addictology. This network of
specific care would notably permit the integrated management of patients
suffering from acute psychiatric disorders or requiring care under constraint.
More specific care networks for particular problems (maternity issues,
adolescence, HIV and hepatitis, cognitive disorders...) and programs of
therapeutic education could reinforce this proposal within a protocol of care
that should be legible, coherent and coordinated. The psychiatrist and the
addictologist must therefore learn to work together over and above the dogmatic
boundaries and positioning in a constructive and efficient partnership,
beneficial for the patient.
PMID- 25113420
TI - Anti-SLA/LP alone or in combination with anti-Ro52 and fine specificity of anti
Ro52 antibodies in patients with autoimmune hepatitis.
AB - BACKGROUND & AIMS: Antibodies (Abs) to soluble liver antigen/liver pancreas (anti
SLA/LP) are considered markers of worse prognosis and outcome in patients with
autoimmune hepatitis (AIH) although this assumption has recently been attributed
to their frequent co-expression with Abs against Ro52 (anti-Ro52). To assess the
clinical significance of anti-SLA/LP Abs alone or in combination with anti-Ro52
in AIH patients and determine the immunodominant Ro52 epitopes according to the
anti-SLA/LP status. METHODS: Twenty-three anti-SLA/LP-positive and 106 anti
SLA/LP-negative AIH patients were included. Anti-SLA/LP were determined by ELISA
using recombinant antigen, and confirmed by immunoblot using cytosolic rat liver
fraction or HuH-7 extract. Anti-Ro52 Abs were determined by ELISA using
recombinant antigen. Epitope mapping was assessed by ELISA using overlapping
peptides covering the whole Ro52 protein in 26 AIH patients and 12 patients with
Sjogren's syndrome. RESULTS: Anti-SLA/LP positivity was not associated with the
clinical, laboratory or histological characteristics of AIH patients. Treatment
response, corticosteroid withdrawal, relapse after stopping treatment and
outcome, were not associated with the presence of anti-SLA/LP, anti-Ro52 or
double reactivity. Moreover, Ro52 epitope mapping revealed new epitopes unique
for AIH and independent from anti-SLA/LP positivity. CONCLUSIONS: Neither anti
SLA/LP nor anti-Ro52 Abs or their combination could specify a distinct group of
AIH patients in terms of clinical characteristics, treatment response and
outcome. Further studies are needed to clarify whether the newly discovered
immunodominant epitopes of Ro52 antigen which were associated specifically with
AIH have any clinical or pathogenetic significance in AIH.
PMID- 25113421
TI - GlycoMaster DB: software to assist the automated identification of N-linked
glycopeptides by tandem mass spectrometry.
AB - Glycosylation is one of the most commonly observed post-translational
modifications (PTMs) in eukaryotes. It is believed that more than 50% eukaryotic
proteins are glycosylated. To reveal the biological functions of protein-linked
glycans involved in numerous biological processes, the high-throughput
identification of both glycoproteins and the attached glycan structures becomes
fundamentally important. Tandem mass spectrometry (MS/MS) is an effective method
for glycoproteomic analysis because of its high sensitivity and selectivity. Two
experimental approaches exist to obtain MS/MS spectral data of glycopeptides. One
consists of isolating glycans from glycopeptides and generating MS/MS spectra of
the glycans and peptides separately. The other approach produces spectra directly
from intact glycopeptides. The latter approach has the advantage of retaining the
glycosylation site information. However, the spectral data cannot be readily
analyzed because of the lack of software specifically designed for the
identification of intact glycopeptides. To address this need, we developed a
novel software tool, GlycoMaster DB, to assist the automated and high-throughput
identification of intact N-linked glycopeptides from MS/MS spectra. The software
simultaneously searches a protein sequence database and a glycan structure
database to find the best pair of peptide and glycan for each input spectrum.
GlycoMaster DB can analyze mass spectral data produced with HCD/ETD mixed
fragmentation, where HCD spectra are used to identify glycans and ETD spectra are
used to determine peptide sequences. When only HCD spectra are available,
GlycoMaster DB can still help to identify the glycans, and a list of possible
peptide sequences are reported according to the accurate precursor mass and the N
linked glycopeptide sequon. GlycoMaster DB is freely accessible at http://www
novo.cs.uwaterloo.ca:8080/GlycoMasterDB .
PMID- 25113423
TI - Fires in Indian hospitals: root cause analysis and recommendations for their
prevention.
AB - There is an increase in the incidence of intraoperative fire in Indian hospitals.
It is hypothesized that oxygen (O2) enrichment of air, is primarily responsible
for most of the fires, particularly in intensive care units. As the amount of
ignition energy needed to initiate fire reduces in the presence of higher O2
concentration, any heat or spark, may be the source of ignition when the air is
O2-rich. The split air conditioner is the source of many such fires in the ICU,
neonatal intensive care unit (NICU), and operating room (OR), though several
other types of equipment used in hospitals have similar vulnerability. Indian
hospitals need to make several changes in the arrangement of equipment and
practice of handling O2 gas, as well as create awareness among hospital staff,
doctors, and administrators. Recommendations for changes in system practice,
which are in conformity with the National Fire Protection Association USA, are
likely to be applicable in preventing fires at hospitals in all developing
countries of the world with warm climates.
PMID- 25113422
TI - Quantification of clonal circulating plasma cells in relapsed multiple myeloma.
AB - The presence of clonal circulating plasma cells (cPCs) remains a marker of high
risk disease in newly diagnosed multiple myeloma (MM) patients. However, its
prognostic utility in MM patients with previously treated disease is unknown. We
studied 647 consecutive patients with previously treated MM seen at the Mayo
Clinic, Rochester who had their peripheral blood evaluated for cPCs by multi
parameter flow cytometry. Of these patients, 145 had actively relapsing disease
while the remaining 502 had disease that was in a plateau and included 68
patients in complete remission (CR) and 434 patients with stable disease.
Patients with actively relapsing disease were more likely to have clonal cPCs
than those in a plateau (P < 0.001). None of the patients in CR had any clonal
cPCs detected. Among patients whose disease was in a plateau, the presence of
clonal cPCs predicted for a worse median survival (22 months vs. not reached; P =
0.004). Among actively relapsing patients, the presence of >=100 cPCs predicted
for a worse survival after flow cytometry analysis (12 months vs. 33 months; P <
0.001). Future studies are needed to determine the role of these findings in
developing a risk-adapted treatment approach in MM patients with actively
relapsing disease.
PMID- 25113424
TI - Retrospective review of predisposing factors for intraoperative pressure ulcer
development.
AB - STUDY OBJECTIVE: To evaluate the comorbidities and surgical factors involved in
the genesis of intraoperative pressure ulcers. DESIGN: Retrospective chart
review. SETTING: Anesthesiology department of a university medical center.
MEASUREMENTS: The charts of 222 patients with varying illness, who underwent an
operation of at least two hours' duration, were analyzed retrospectively. Data on
surgery type, case length, comorbidities, intraoperative surgical position, and
area of ulceration were recorded. MAIN RESULTS: Risk factors for intraoperative
pressure ulcer development include surgical times of 4 hours or longer;
comorbidities affecting tissue perfusion (namely, diabetes, hypertension, and
nonspecific cardiac issues); supine placement during surgery; and abdominal,
noncardiac thoracic, and orthopedic operations. Regions of the body most at risk
for ulceration include the coccygeal/sacral region, the buttocks, genitalia, and
heels. CONCLUSIONS: Pressure ulcers are a costly, debilitating, and avoidable
complication of surgery.
PMID- 25113425
TI - Which nostril should be used for nasotracheal intubation: the right or left? A
randomized clinical trial.
AB - STUDY OBJECTIVE: To determine which nostril is more suitable for nasotracheal
intubation in patients with normal patency of both nostrils. DESIGN: Prospective,
randomized clinical trial. SETTING: Operating room of a university medical
center. PATIENTS: 191 ASA physical status 1 and 2 patients scheduled for elective
oral surgery requiring general anesthesia with nasotracheal intubation.
INTERVENTIONS: Patients were randomized to two groups to undergo nasotracheal
intubation through the right nostril (Group R; n = 96) or the left nostril (n =
95). Standard traditional nasotracheal intubation was performed using the
Macintosh laryngoscope. Tube rotation was attempted for alignment toward the
glottis, and Magill forceps were then used to assist intubation, as necessary.
MEASUREMENTS: Epistaxis was inspected in the pharynx after the tube tip was
passed through the nasal cavity and 15 minutes after nasotracheal intubation was
completed. Intubation time was the interval between when the anesthesiologist
opened the patient's mouth with the cross finger maneuver and when the tube was
connected to the anesthetic circuit after nasotracheal completion. MAIN RESULTS:
The frequency of epistaxis was significantly lower in Group R than Group L (P =
0.0006). Although there was no significant difference in nasal passage time
between two groups, the intubation time in Group R (24.5 +/- 9.4 sec) was shorter
than in Group L (30.5 +/- 15.6 sec; P = 0.0015). CONCLUSION: Nasal intubation via
the right nostril is more safely performed than with the left nostril. Because of
less epistaxis and faster intubation.
PMID- 25113426
TI - The effects of physical and geochemical heterogeneities on hydro-geochemical
transport and effective reaction rates.
AB - The role of coupled physical and geochemical heterogeneities in hydro-geochemical
transport is investigated by simulating three-dimensional transport in a
heterogeneous system with kinetic mineral reactions. Ensembles of 100 physically
heterogeneous realizations were simulated for three geochemical conditions: 1)
spatially homogeneous reactive mineral surface area, 2) reactive surface area
positively correlated to hydraulic heterogeneity, and 3) reactive surface area
negatively correlated to hydraulic heterogeneity. Groundwater chemistry and the
corresponding effective reaction rates were calculated at three transverse planes
to quantify differences in plume evolution due to heterogeneity in mineral
reaction rates and solute residence time (tau). The model is based on a
hypothetical CO2 intrusion into groundwater from a carbon capture utilization and
storage (CCUS) operation where CO2 dissolution and formation of carbonic acid
created geochemical dis-equilibrium between fluids and the mineral galena that
resulted in increased aqueous lead (Pb(2+)) concentrations. Calcite dissolution
buffered the pH change and created conditions of galena oversaturation, which
then reduced lead concentrations along the flow path. Near the leak kinetic
geochemical reactions control the release of solutes into the fluid, but further
along the flow path mineral solubility controls solute concentrations. Simulation
results demonstrate the impact of heterogeneous distribution of geochemical
reactive surface area in coordination with physical heterogeneity on the
effective reaction rate (Krxn,eff) and Pb(2+) concentrations within the plume.
Dissimilarities between ensemble Pb(2+) concentration and Krxn,eff are attributed
to how geochemical heterogeneity affects the time (taueq) and therefore advection
distance (Leq) required for the system to re-establish geochemical equilibrium.
Only after geochemical equilibrium is re-established, Krxn,eff and Pb(2+)
concentrations are the same for all three geochemical conditions. Correlation
between reactive surface area and hydraulic conductivity, either positive or
negative, results in variation in taueq and Leq.
PMID- 25113427
TI - The external use of comfrey: a practitioner survey.
AB - AIM: The survey aimed to assess how often and in what ways herbal practitioners
use comfrey (Symphytum officinale L.) externally in everyday practice. METHODS: A
2-sided A4 survey was sent to all UK members of the National Institute of Medical
Herbalists, the College of Practitioners of Phytotherapy and the Association of
Master Herbalists with viable practice addresses (n = 598). RESULTS: 239
herbalists responded, of whom 179 (75%) reported regularly using comfrey, in 15%
of their consultations. It was most commonly prescribed as a cream for tendon,
ligament and muscle problems, for fractures, and for wounds, the indications for
which it was also perceived to be most effective. Comfrey was rated least
effective for haemorrhoids, varicose veins and boils and was considered to carry
the greatest risk when prescribed for ulcers, wounds and boils. CONCLUSION:
Practitioner experience suggests that comfrey can be used safely and effectively
externally for certain indications.
PMID- 25113428
TI - Long-term inverse modeling of Chinese CO emission from satellite observations.
AB - Carbon monoxide (CO) emissions in China in 2005-2010 were estimated by inversion,
using the Green's function method from vertical CO profiles derived from MOPITT
Version 5 satellite data and a tagged CO simulation, and validated with
independent in situ observations from the World Data Centre for Greenhouse Gases.
Modeling with a posteriori emission successfully reproduced CO outflow from the
continent to the East China Sea, Sea of Japan, and Japanese islands during winter
and spring, and compensated for underestimates in central and eastern China in
summer. A posteriori emissions showed large seasonal variations in which December
and March emissions were on average 23% larger than August emissions, consistent
with other studies. Estimated Chinese CO emissions were 184.4, 173.1, 184.6,
158.4, 157.4, and 157.3 Tg/year for 2005-2010, respectively. The decrease after
2007 is partly attributed to Chinese socioeconomic conditions and improved
combustion efficiency.
PMID- 25113429
TI - Crystallization and its effect on the mechanical properties of a medium chain
length polyhydroxyalkanoate.
AB - Medium chain length polyhydroxyalkanoates (mcl-PHAs) could play a role in the
growing demand for highly elastic and biodegradable materials in the medical
field. In this study, a poly(3-hydroxyoctanoate-co-3-hydroxyhexanoate) (P(3HO-co
3HH)) was first fully characterized in terms of molecular weight, microstructural
chain parameters and chemical structure by means of gel permeation chromatography
(GPC), nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR). As
determined by NMR, the synthesized polymer contained 94.3% and 5.7% molar content
of 3-hydroxyoctanoate and 3-hydroxyhexanoate, respectively. Since mechanical
properties are closely related to thermal history, the effect of crystallization
on tensile properties was also investigated in the present study. Three
crystallization temperatures were selected (0, 23 and 37 degrees C), the
conclusion reached is that the maximum crystallization rate for this copolymer
was achieved at 0 degrees C. On the other hand, evolution of tensile properties
of P(3HO-co-3HH) films stored at room temperature demonstrated that, as
crystallization occurred toward the equilibrium state, the polymer underwent a
stiffening process. In this sense, secant modulus and tensile strength increased
respectively from 8.3 +/- 1.0 MPa and 6.4 +/- 0.8 MPa after 1 day stored at room
temperature to 36.2 +/- 3.3 MPa and 16.3 +/- 2.1 MPa after 16 weeks.
PMID- 25113430
TI - Targeted SLNs for management of HIV-1 associated dementia.
AB - CONTEXT: HIV-1 associated dementia (HAD) is an evolving disease in the category
of neurological disorders. OBJECTIVE: Nifedipine-loaded solid lipid nanoparticles
(SLNs) were developed and coated with Tween 80 to facilitate enhanced brain drug
delivery for the treatment of HAD. MATERIALS AND METHODS: SLNs were prepared
using solvent injection method. Lipids consisted of tristearin, hydrogenated soya
phosphatidylcholine (HSPC) (1.5:1 w/w). Nifedipine was model drug in this study.
Tween 80 (0.5% v/v) was taken as key modulator. SLNs were characterized for
particle shape, size, zeta potential, entrapment efficiency, in vitro drug
release, DNA fragmentation, cytotoxicity potential and in vivo studies. RESULTS:
The SLNs (plain and coated) were found to be in nanometric in size (~120 nm) with
more than 70% entrapment efficiency. In vitro drug release profile reflected
sustained release up to 48 h. Tween 80-coated SLNs showed higher percentage of
DNA fragmentation in vitro and enhanced cell viability in sulforhodamine assay
(rat cortical cells) as compared to plain drug and uncoated SLNs due to
facilitated uptake of SLNs and reversal of P-gp efflux by virtue of Tween 80.
Biodistribution study performed on vital organs, i.e. brain, heart, liver,
spleen, lungs and kidney showed increased accumulation of Tween 80-coated SLNs in
the brain. DISCUSSION AND CONCLUSION: Tween 80 enhanced localization of SLNs in
the brain as compared to uncoated SLNs. This approach can be employed effectively
to transport chemotherapeutics across the BBB for management of HIV-1 associated
dementia and other ailments.
PMID- 25113431
TI - Development of ocular drug delivery systems using molecularly imprinted soft
contact lenses.
AB - Recently, significant advances have been made in order to optimize drug delivery
to ocular tissues. The main problems in ocular drug delivery are poor
bioavailability and uncontrollable drug delivery of conventional ophthalmic
preparations (e.g. eye drops). Hydrogels have been investigated since 1965 as new
ocular drug delivery systems. Increase of hydrogel loading capacity, optimization
of drug residence time on the ocular surface and biocompatibility with the eye
tissue has been the main focus of previous studies. Molecular imprinting
technology provided the opportunity to fulfill the above-mentioned objectives.
Molecularly imprinted soft contact lenses (SCLs) have high potentials as novel
drug delivery systems for the treatment of eye disorders. This technique is used
for the preparation of polymers with specific binding sites for a template
molecule. Previous studies indicated that molecular imprinting technology could
be successfully applied for the preparation of SCLs as ocular drug delivery
systems. Previous research, particularly in vivo studies, demonstrated that
molecular imprinting is a versatile and effective method in optimizing the drug
release behavior and enhancing the loading capacity of SCLs as new ocular drug
delivery systems. This review highlights various potentials of molecularly
imprinted contact lenses in enhancing the drug-loading capacity and controlling
the drug release, compared to other ocular drug delivery systems. We have also
studied the effects of contributing factors such as the type of comonomer,
template/functional monomer molar ratio, crosslinker concentration in drug
loading capacity, and the release properties of molecularly imprinted hydrogels.
PMID- 25113432
TI - Enhancement of the oral bioavailability of breviscapine by nanoemulsions drug
delivery system.
AB - Aim to design an effective breviscapine nanoscale drug delivery system to realize
the improvement of its oral bioavailability. Based on the investigations of the
stabilities in the gastrointestinal tract (GIT), permeation and efflux across the
cell membrane, the breviscapine nanoemulsion (NE) was formulated and evaluated in
vitro and in vivo. The globule size and polydispersity index of the NE was 45.6
nm and 0.105, and the efficient encapsulation was 95.2%. In vitro, the drug
release from NEs in pH 6.8 PBS fit to the first-order kinetics. The Caco-2 cell
transport experiments showed that the breviscapine NE facilitated the improvement
of the apparent permeability coefficient (Papp) from the apical side to basilar
side compared with the free drug. In vivo, the relative bioavailability of
breviscapine NE reached to 249.7%. All the studies implicated that the NE carrier
contributed to the enhancement of the oral absorption of breviscapine due to the
improved stability and permeation in the GIT. The nanoemulsions technology is
better for the poor permeable and unstable active agents in GIT as well as helps
the industrial scale process.
PMID- 25113435
TI - Synthesis and characterization of inorganic-organic hybrid gallium selenides.
AB - Two semiconducting hybrid gallium selenides, [Ga6Se9(C6H14N2)4][H2O] (1) and
[C6H14N2][Ga4Se6(C6H14N2)2] (2), were prepared using a solvothermal method in the
presence of 1,2-diaminocyclohexane (1,2-DACH). Both materials consist of neutral
inorganic layers, in which 1,2-DACH is covalently bonded to gallium. In 1, the
organic amine acts as a monodentate and a bidentate ligand, while in 2, bidentate
and uncoordinated 1,2-DACH molecules coexist.
PMID- 25113436
TI - Optical coherence tomography-based retinal vessel analysis for the evaluation of
hypertensive vasculopathy.
AB - PURPOSE: Evaluation of retinal vessels in cardiovascular disease traditionally
relies upon funduscopy, but more recently digital photo analysis has expanded the
spectrum. As spectral domain optical coherence tomography (OCT) allows an in-vivo
assessment of retinal tissue and its vessels on a histological scale, our study
aimed at using this tool for the analysis of the retinal vasculature. METHODS:
Circumferential peripapillary OCT scans (3DOCT-2000; Topcon Inc., Tokyo, Japan),
with centration on the optic nerve head, were taken from 20 eyes (20
participants) with normal blood pressure and 20 eyes (20 participants) with
arterial hypertension above 120 mmHg (mean blood pressure). The diameter of all
vessels intersecting the scan line was measured in the OCT and used to calculate
central vessel equivalents, and the A/V ratios were calculated. Bland-Altman
analysis was performed to evaluate reliability. Correlation coefficients were
determined for reliability of the method as well as with the individual mean
arterial blood pressures. RESULTS: Forty eyes (40 participants) were included in
the study. Mean arterial blood pressure was 96+/-4 mmHg in the control group and
132+/-7 mmHg in the hypertonic group. Mean A/V ratio as determined from OCT scans
was 0.82+/-0.13 (normotonic) versus 0.62+/-0.11 (hypertonic). A Pearson's
correlation coefficient of 0.67 (p<0.001) was determined between A/V ratio and
blood pressure. CONCLUSIONS: Our results highlight the feasibility of retinal
vessel measurements in spectral domain OCT. A relation between mean arterial
blood pressure and OCT-based A/V ratio was established. Further research will
elucidate influencing factors and provide a broader basis for therapeutic
approaches.
PMID- 25113434
TI - A meta-analysis of the relationship between trait mindfulness and substance use
behaviors.
AB - BACKGROUND: The relationship between trait mindfulness and substance use
behaviors has been inconsistent across studies. The current meta-analysis aimed
at quantifying the magnitude of this relationship, and at determining how this
relationship varies in context of (1) mindfulness facets, (2) substance type, (3)
sample characteristics, and (4) substance use severity. METHODS: Using electronic
databases, the literature search yielded 303 articles, but only 39 articles met
inclusion criteria to be included in this meta-analysis. The relationship was
quantified as a Pearson's r correlation coefficient for all studies. RESULTS:
Findings indicated a small, negative, and significant trait mindfulness-substance
use behaviors relationship (r=-0.13). This relationship varied across substance
type, clinical status of the sample, and substance use severity. Mindfulness
facet was not a significant moderator; however, only particular facets (e.g.,
acting with awareness, non-judgment, and non-reactivity) were consistently
associated with substance use behaviors. CONCLUSIONS: This meta-analysis
quantified the trait mindfulness-substance use behaviors relationship, which can
be used as future effect size estimates. Findings also indicated that the trait
mindfulness-substance use behaviors relationship was more robust: (1) for alcohol
and tobacco use compared to marijuana use behaviors; (2) for problematic compared
to non-problematic substance use behaviors; and (3) with inpatient compared to
outpatient and non-clinical samples. Further work should continue to examine if
acting with awareness, non-judgment, and non-reactivity mindfulness facets are
more robustly associated with substance use behaviors. Failure to consider these
factors, or collapsing across these factors, could explain the smaller or
inconsistently reported associations across previous studies.
PMID- 25113437
TI - Dehydrative cross-coupling reactions of allylic alcohols with olefins.
AB - The direct dehydrative activation of allylic alcohols and subsequent cross
coupling with alkenes by using palladium catalyst containing a phosphoramidite
ligand is described. The activation of the allyl alcohol does not require
stoichiometric additives, thus allowing clean, waste-free reactions. The scope is
demonstrated by application of the protocol to a series allylic alcohols and
vinyl arenes, leading to variety of 1,4-diene products. Based on kinetic studies,
a mechanism is proposed that involves a palladium hydride species that activates
the allyl alcohol to form the allyl intermediate.
PMID- 25113438
TI - Factors that characterize bone health with aging in healthy postmenopausal women.
AB - The exponential increase in the incidence of fragility fractures in older people
is attributed to attenuation of both bone strength and neuromuscular function.
Decrease in bone mineral density (BMD) does not entirely explain this increase.
The objective of this study is to investigate the effect of age on various
parameters related to bone health with aging, and to identify combinations of
factors that collectively express the bone metabolic state in healthy
postmenopausal women. Height, weight, and grip strength were measured in 135
healthy postmenopausal volunteer women. Hip BMD, biomechanical indices derived
from quantitative computed tomography (QCT), cross-sectional areas of muscle and
fat of the proximal thigh, and various biochemical markers of bone metabolism
were measured. A smaller group of factors explanatory for bone health was
identified using factor analysis and each was newly named. As a result, the
factors bone mass, bone turnover, bone structure, and muscle strength had the
greatest explanatory power for assessing the bone health of healthy
postmenopausal women. Whereas dual X-ray absorptiometry parameters only loaded on
the factor bone mass, QCT parameters loaded on both the factors bone mass and
bone structure. Most bone turnover markers loaded on the factor bone turnover,
but deoxypyridinoline loaded on both bone turnover and muscle strength. Age was
negatively correlated with bone mass (r = -0.49, p < 0.001) and muscle strength
(r = -0.67, p < 0.001). We conclude that aging is associated as much with muscle
weakening as with low BMD. More attention should be paid to the effects of muscle
weakening during aging in assessments of bone health.
PMID- 25113439
TI - Regulatory T cells with CD62L or TNFR2 expression in young type 1 diabetic
patients: relation to inflammation, glycemic control and micro-vascular
complications.
AB - BACKGROUND: Alteration of regulatory T cells (Tregs) may contribute to
ineffective suppression of proinflammatory cytokines in type 1 diabetes. AIM: We
determined the percentage of Tregs expressing CD62L or tumor necrosis factor
receptor type 2 (TNFR2) in 70 young type 1 diabetic patients compared with 30
controls and assessed their relation to inflammation, glycemic control and micro
vascular complications. METHODS: High-sensitivity C-reactive protein (hs-CRP),
hemoglobin A1c (HbA1c), tumor necrosis factor alpha (TNF-alpha) and interleukin
10 (IL-10) were assessed with flow cytometric analysis of Tregs, Tregs expressing
CD62L or TNFR2. RESULTS: The percentage of CD4(+)CD25(high) T cells and
CD4(+)CD25(high)CD62L(high) cells were significantly decreased while
CD4(+)CD25(high)TNFR2(+) T cells were elevated in patients with micro-vascular
complications than those without and controls (p<0.001). ROC curve revealed that
the cutoff values of Tregs, Tregs expressing CD62L and Tregs expressing TNFR2
(7.46%, 24.2% and 91.9%, respectively) could detect micro-vascular complications.
Significant negative correlations were observed between Tregs expressing CD62L
and disease duration, FBG, HbA1c, urinary albumin excretion and hs-CRP, whereas,
positive correlations were found between Tregs expressing TNFR2 and these
variables (p<0.05). TNF-alpha was significantly increased while IL-10 was
decreased among patients with micro-vascular complications than those without
(p<0.05). CONCLUSIONS: Alteration in the frequency of Tregs and Tregs expressing
CD62L or TNFR2 in type 1 diabetes is associated with increased inflammation, poor
glycemic control and risk of micro-vascular complications.
PMID- 25113441
TI - A two-hybrid screen identifies an unconventional role for the intermediate
filament peripherin in regulating the subcellular distribution of the SNAP25
interacting protein, SIP30.
AB - Peripherin is a type III intermediate filament protein, the expression of which
is associated with the acquisition and maintenance of a terminally differentiated
neuronal phenotype. Peripherin up-regulation occurs during acute neuronal injury
and in degenerating motor neurons of amyotrophic lateral sclerosis. The
functional role(s) of peripherin during normal, injurious, and disease conditions
remains unknown, but may be related to differential expression of spliced
isoforms. To better understand peripherin function, we performed a yeast two
hybrid screen on a mouse brain cDNA library using an assembly incompetent
peripherin isoform, Per-61, as bait. We identified new peripherin interactors
with roles in vesicular trafficking, signal transduction, DNA/RNA processing,
protein folding, and mitochondrial metabolism. We focused on the interaction of
Per-61 and the constitutive isoform, Per-58, with SNAP25 interacting protein 30
(SIP30), a neuronal protein involved in SNAP receptor-dependent exocytosis. We
found that peripherin and SIP30 interacted through coiled-coil domains and
colocalized in cytoplasmic aggregates in SW13vim(-) cells. Interestingly, Per-61
and Per-58 differentially altered the subcellular distribution of SIP30 and
SNAP25 in primary motor neurons. Our findings suggest a novel role of peripherin
in vesicle trafficking.
PMID- 25113440
TI - Mutational and functional analysis of the tumor-suppressor PTPRD in human
melanoma.
AB - Protein tyrosine phosphatases (PTPs) tightly regulate tyrosine phosphorylation
essential for cell growth, adhesion, migration, and survival. We performed a
mutational analysis of the PTP gene family in cutaneous metastatic melanoma and
identified 23 phosphatase genes harboring somatic mutations. Among these,
receptor-type tyrosine-protein phosphatase delta (PTPRD) was one of the most
highly mutated genes, harboring 17 somatic mutations in 79 samples, a prevalence
of 21.5%. Functional evaluation of six PTPRD mutations revealed enhanced
anchorage-dependent and anchorage-independent growth. Interestingly, melanoma
cells expressing mutant PTPRD were significantly more migratory than cells
expressing wild-type PTPRD or vector alone, indicating a novel gain-of-function
associated with mutant PTPRD. To understand the molecular mechanisms of PTPRD
mutations, we searched for its binding partners by converting the active PTPRD
enzyme into a "substrate trap" form. Using mass spectrometry and
coimmunoprecipitation, we report desmoplakin, a desmosomal protein that is
implicated in cell-cell adhesion, as a novel PTPRD substrate. Further analysis
showed reduced phosphatase activity of mutant PTPRD against desmoplakin. Our
findings identify an essential signaling cascade that is disrupted in melanoma.
Moreover, because PTPRD is also mutated in glioblastomas and adenocarcinoma of
the colon and lung, our data might be applicable to a large number of human
cancers.
PMID- 25113442
TI - Ophthalmologic impairment during adulthood in central congenital hypoventilation
syndrome: a longitudinal cohort analysis of nine patients.
AB - BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare
dysgenetic form of neurocristopathy associated with dysfunction of the autonomic
nervous system. Ophthalmologic abnormalities are reported in CCHS children, and
range from pupillary and iris abnormalities to ptosis, strabismus and convergence
deficiency. Since earlier CCHS diagnosis and multidisciplinary management,
combined with improved ventilatory support techniques, the lifespan of children
with CCHS has been considerably lengthened. The oldest of them have now reached
adult age and we report in this study the results of their ophthalmologic
examination. MATERIALS AND METHODS: Nine CCHS adult patients were prospectively
included during a 14-month period. Each patient underwent complete ophthalmologic
examination, static pupillometry with scotopic and photopic pupillary diameter
(PD) measures, Humphrey 24-2 visual field analysis, macular OCT and complete
orthoptic assessment including a Hess-Lancaster test. RESULTS: Ophthalmologic
abnormalities were found in six of the nine patients (66%). The main features
were strabismus in six patients (66%). Four patients (44%) displayed abnormal
pupillary function, with a decrease in average scotopic PD (3.8 +/- 1.4 mm),
average photopic PD (3.5 +/- 1.2 mm), and average percentage of pupillary
constriction (7.6 +/- 8.5%). Three patients (33%) exhibited iris abnormalities
such as iris atrophy, smooth iris surface and atrophic sphincter. CONCLUSION:
This study allowed the description of ophthalmologic abnormalities occurring in
CCHS in a series of adult patients, thus improving current knowledge of the
disease. The prevalence of pupillary and iris lesions were lower than those
observed in a series of children, suggesting that they could be considered as
systemic disease severity markers.
PMID- 25113445
TI - Lessons from crop plants struggling with salinity.
AB - Salinity is a persistent problem, causing important losses in irrigated
agriculture. According to global climate change prediction models, salinity is
expected to expand in the near future. Although intensive studies have been
conducted on the mechanisms by which plants cope with saline conditions, the
multi-component nature of salt stress tolerance has rendered most plant breeding
efforts to improve the plant's response to salinity unsuccessful. This occurs
despite the extensive genetic diversity shown by higher plants for salt tolerance
and the similar mechanisms found in salt-sensitive and salt-tolerant genotypes in
response to the presence of excess of salts in the growth media. On the other
hand, there is an urge to increase crop yield to the maximum to cope with the
growing world population demands for food and fuel. Here, we examine some major
elements and signaling mechanisms involved in the plant's response to salinity
following the pathway of salt-footprints from the soil environment to leaf. Some
of the possible contrasting determinants for a better-balanced resource
allocation between salt tolerance and plant growth and yield are considered.
PMID- 25113446
TI - Mechanistic insights on the responses of plant and ecosystem gas exchange to
global environmental change: lessons from Biosphere 2.
AB - Scaling up leaf processes to canopy/ecosystem level fluxes is critical for
examining feedbacks between vegetation and climate. Collectively, studies from
Biosphere 2 Laboratory have provided important insight of leaf-to-ecosystem
investigations of multiple environmental parameters that were not before possible
in enclosed or field studies. B2L has been a testing lab for the applicability of
new technologies such as spectral approaches to detect spatial and temporal
changes in photosynthesis within canopies, or for the development of cavity ring
down isotope applications for ecosystem evapotranspiration. Short and long term
changes in atmospheric CO2, drought or temperature allowed for intensive
investigation of the interactions between photosynthesis and leaf, soil and
ecosystem respiration. Experiments conducted in the rainforest biome have
provided some of the most comprehensive dataset to date on the effects of climate
change variables on tropical ecosystems. Results from these studies have been
later corroborated in natural rainforest ecosystems and have improved the
predictive capabilities of models that now show increased resilience of tropics
to climate change. Studies of temperature and CO2 effects on ecosystem
respiration and its leaf and soil components have helped reconsider the use of
simple first-order kinetics for characterizing respiration in models. The B2L
also provided opportunities to quantify the rhizosphere priming effect, or
establish the relationships between net primary productivity, atmospheric CO2 and
isoprene emissions.
PMID- 25113443
TI - Novel C8orf37 Mutations in Patients with Early-onset Retinal Dystrophy, Macular
Atrophy, Cataracts, and High Myopia.
AB - PURPOSE: More than 50 genes are reported as causative genes of autosomal
recessive (ar) retinitis pigmentosa (RP) and cone-rod dystrophy (CRD). It is
challenging to identify causative mutations for arRP and arCRD. The purpose of
the present study was to investigate clinical and genetic features of two
siblings with early-onset retinal dystrophy. METHODS: Whole-exome sequencing was
conducted for the two affected siblings and their unaffected brother and mother
from a Japanese family. We performed complete ophthalmic examinations, including
visual acuity, funduscopy, visual-field testing, electroretinography and optical
coherence tomography. RESULTS: Whole-exome sequencing analysis identified novel
compound heterozygous mutations, a splice site mutation (c.374 + 2T > C in intron
4) and a deletion mutation (c.575delC [p.T192MfsX28] in exon 6) of chromosome 8
open reading frame 37 (C8orf37) gene, which encodes a ciliary protein, in both
patients. The mother carried the truncating mutation, and the brother carried
neither mutation. Ophthalmic examinations revealed diffuse retinal degeneration,
macular atrophy, non-recordable electroretinography responses, cataracts, and
high myopia in both patients, who could not be diagnosed with either RP or CRD
because of the severe retinal degeneration and early onset disease. Longitudinal
follow-up of the patients revealed highly progressive retinal degeneration,
macular atrophy, and visual field loss. CONCLUSIONS: Recessive C8orf37 mutations
have been identified in early to adolescent-onset arRP and arCRD with macular
involvement. Our study identified two novel truncating mutations of the C8orf37
gene in siblings with early-onset retinal dystrophy, macular atrophy, cataracts,
and high myopia.
PMID- 25113447
TI - Growth, photosynthetic acclimation and yield quality in legumes under climate
change simulations: an updated survey.
AB - Continued emissions of CO2, derived from human activities, increase atmospheric
CO2 concentration. The CO2 rise stimulates plant growth and affects yield
quality. Effects of elevated CO2 on legume quality depend on interactions with N2
fixing bacteria and mycorrhizal fungi. Growth at elevated CO2 increases
photosynthesis under short-term exposures in C3 species. Under long-term
exposures, however, plants generally acclimate to elevated CO2 decreasing their
photosynthetic capacity. An updated survey of the literature indicates that a key
factor, perhaps the most important, that characteristically influences this
phenomenon, its occurrence and extent, is the plant source-sink balance. In
legumes, the ability of exchanging C for N at nodule level with the N2-fixing
symbionts creates an extra C sink that avoids the occurrence of photosynthetic
acclimation. Arbuscular mycorrhizal fungi colonizing roots may also result in
increased C sink, preventing photosynthetic acclimation. Defoliation (Anthyllis
vulneraria, simulated grazing) or shoot cutting (alfalfa, usual management as
forage) largely increases root/shoot ratio. During re-growth at elevated CO2, new
shoots growth and nodule respiration function as strong C sinks that counteracts
photosynthetic acclimation. In the presence of some limiting factor, the legumes
response to elevated CO2 is weakened showing photosynthetic acclimation. This
survey has identified limiting factors that include an insufficient N supply from
bacterial strains, nutrient-poor soils, low P supply, excess temperature
affecting photosynthesis and/or nodule activity, a genetically determined low
nodulation capacity, an inability of species or varieties to increase growth (and
therefore C sink) at elevated CO2 and a plant phenological state or season when
plant growth is stopped.
PMID- 25113448
TI - Methodological advances: using greenhouses to simulate climate change scenarios.
AB - Human activities are increasing atmospheric CO2 concentration and temperature.
Related to this global warming, periods of low water availability are also
expected to increase. Thus, CO2 concentration, temperature and water availability
are three of the main factors related to climate change that potentially may
influence crops and ecosystems. In this report, we describe the use of growth
chamber - greenhouses (GCG) and temperature gradient greenhouses (TGG) to
simulate climate change scenarios and to investigate possible plant responses. In
the GCG, CO2 concentration, temperature and water availability are set to act
simultaneously, enabling comparison of a current situation with a future one.
Other characteristics of the GCG are a relative large space of work, fine control
of the relative humidity, plant fertirrigation and the possibility of light
supplementation, within the photosynthetic active radiation (PAR) region and/or
with ultraviolet-B (UV-B) light. In the TGG, the three above-mentioned factors
can act independently or in interaction, enabling more mechanistic studies aimed
to elucidate the limiting factor(s) responsible for a given plant response.
Examples of experiments, including some aimed to study photosynthetic
acclimation, a phenomenon that leads to decreased photosynthetic capacity under
long-term exposures to elevated CO2, using GCG and TGG are reported.
PMID- 25113450
TI - Inconsistency of mesophyll conductance estimate causes the inconsistency for the
estimates of maximum rate of Rubisco carboxylation among the linear, rectangular
and non-rectangular hyperbola biochemical models of leaf photosynthesis--a case
study of CO2 enrichment and leaf aging effects in soybean.
AB - The responses of CO2 assimilation to [CO2] (A/Ci) were investigated at two
developmental stages (R5 and R6) and in several soybean cultivars grown under two
levels of CO2, the ambient level of 370 MUbar versus the elevated level of 550
MUbar. The A/Ci data were analyzed and compared by either the combined iterations
or the separated iterations of the Rubisco-limited photosynthesis (Ac) and/or the
RuBP-limited photosynthesis (Aj) using various curve-fitting methods: the linear
2-segment model; the non-rectangular hyperbola model; the rectangular hyperbola
model; the constant rate of electron transport (J) method and the variable J
method. Inconsistency was found among the various methods for the estimation of
the maximum rate of carboxylation (Vcmax), the mitochondrial respiration rate in
the light (Rd) and mesophyll conductance (gm). The analysis showed that the
inconsistency was due to inconsistent estimates of gm values that decreased with
an instantaneous increase in [CO2], and varied with the transition Ci cut-off
between Rubisco-limited photosynthesis and RuBP-regeneration-limited
photosynthesis, and due to over-parameters for non-linear curve-fitting with gm
included. We proposed an alternate solution to A/Ci curve-fitting for estimates
of Vcmax, Rd, Jmax and gm with the various A/Ci curve-fitting methods. The study
indicated that down-regulation of photosynthetic capacity by elevated [CO2] and
leaf aging was due to partially the decrease in the maximum rates of
carboxylation and partially the decrease in gm. Mesophyll conductance lowered
photosynthetic capacity by 18% on average for the case of soybean plants.
PMID- 25113449
TI - Stomatal and mesophyll conductances to CO2 in different plant groups: underrated
factors for predicting leaf photosynthesis responses to climate change?
AB - The climate change conditions predicted for the end of the current century are
expected to have an impact on the performance of plants under natural conditions.
The variables which are foreseen to have a larger effect are increased CO2
concentration and temperature. Although it is generally considered CO2
assimilation rate could be increased by the increasing levels of CO2, it has been
reported in previous studies that acclimation to high CO2 results in reductions
of physiological parameters involved in photosynthesis, like the maximum
carboxylation rate (Vc,max), stomatal conductance (gs) and mesophyll conductance
to CO2 (gm). On the one hand, most of the previous modeling efforts have
neglected the potential role played by the acclimation of gm to high CO2 and
temperature. On the other hand, the effect of climate change on plant clades
other than angiosperms, like ferns, has received little attention, and there are
no studies evaluating the potential impact of increasing CO2 and temperature on
these species. In this study we predicted responses of several representative
species among angiosperms, gymnosperms and ferns to increasing CO2 and
temperature. Our results show that species with lower photosynthetic capacity -
such as some ferns and gymnosperms - would be proportionally more favored under
these foreseen environmental conditions. The main reason for this difference is
the lower diffusion limitation imposed by gs and gm in plants having high
capacity for photosynthesis among the angiosperms, which reduces the positive
effect of increasing CO2. However, this apparent advantage of low-diffusion
species would be canceled if the two conductances - gs and gm - acclimate and are
down regulated to high CO2, which is basically unknown, especially for
gymnosperms and ferns. Hence, for a better understanding of different plant
responses to future climate, studies are urged in which the actual photosynthetic
response/acclimation to increased CO2 and temperature of ferns, gymnosperms and
other under-evaluated plant groups is assessed.
PMID- 25113451
TI - Rubisco catalytic properties optimized for present and future climatic
conditions.
AB - Because of its catalytic inefficiencies, Rubisco is the most obvious target for
improvement to enhance the photosynthetic capacity of plants. Two hypotheses are
tested in the present work: (1) existing Rubiscos have optimal kinetic properties
to maximize photosynthetic carbon assimilation in existing higher plants; (2)
current knowledge allows proposal of changes to kinetic properties to make
Rubiscos more suited to changed conditions in chloroplasts that are likely to
occur with climate change. The catalytic mechanism of Rubisco results in higher
catalytic rates of carboxylation being associated with decreased affinity for
CO2, so that selection for different environments involves a trade-off between
these two properties. The simulations performed in this study confirm that the
optimality of Rubisco kinetics depends on the species and the environmental
conditions. In particular, environmental drivers affecting the CO2 availability
for carboxylation (Cc) or directly shifting the photosynthetic limitations
between Rubisco and RuBP regeneration determine to what extend Rubisco kinetics
are optimally suited to maximize CO2 assimilation rate. In general, modeled
values for optimal kinetic reflect the predominant environmental conditions
currently encountered by the species in the field. Under future climatic
conditions, photosynthetic CO2 assimilation will be limited by RuBP-regeneration,
especially in the absence of water stress, the largest rise in [CO2] and the
lowest increases in temperature. Under these conditions, the model predicts that
optimal Rubisco should have high Sc/o and low kcat(c).
PMID- 25113452
TI - Will carbon isotope discrimination be useful as a tool for analysing the
functional response of barley plants to salinity under the future atmospheric CO2
conditions?
AB - The objective of this study was to determine the response of barley's carbon
isotope composition and other physiological parameters to the interaction of salt
stress and elevated CO2 levels, and the usefulness of carbon isotope
discrimination (Delta(13)C) as indicative of the functional performance of barley
(Hordeum vulgare L.). Barley plants were grown under ambient (350 MUmol mol(-1))
and elevated (700 MUmol mol(-1)) CO2 conditions and subjected to salt stress (0,
80, 160, and 240 mM NaCl) for 14 days. Elevated CO2 levels increased biomass
production, water use efficiency and the photosynthetic rate, although this
parameter was partly acclimated to elevated CO2 levels. Salt stress decreased
this acclimation response because it enhanced the sink strength of the plant.
Elevated CO2 significantly decreased the (13)C isotopic composition (delta(13)C)
in all plant organs; however, the ratio of delta(13)C between the root and the
leaf was increased, indicating a higher allocation of delta(13)C to the below
ground parts. Conversely, salt stress increased plant delta(13)C, showing
differences between plant organs. From the strong correlations between Delta(13)C
and biomass production, the photosynthetic rate or water use efficiency both at
ambient and elevated CO2, we concluded that Delta(13)C is a useful parameter for
evaluating leaf and whole plant responses to salinity and can provide an
integrated index of processes to understand the mechanisms underlying salt
tolerance of barley both under current and future environmental CO2 conditions.
PMID- 25113453
TI - Isoprene emission aids recovery of photosynthetic performance in transgenic
Nicotiana tabacum following high intensity acute UV-B exposure.
AB - Isoprene emission by terrestrial plants is believed to play a role in mitigating
the effects of abiotic stress on photosynthesis. Ultraviolet-B light (UV-B)
induces damage to the photosynthetic apparatus of plants, but the role of
isoprene in UV-B tolerance is poorly understood. To investigate this putative
protective role, we exposed non-emitting (NE) control and transgenic isoprene
emitting (IE) Nicotiana tabacum (tobacco) plants to high intensity UV-B exposure.
Methanol emissions increased with UV-B intensity, indicating oxidative damage.
However, isoprene emission was unaffected during exposure to UV-B radiation, but
declined in the 48 h following UV-B treatment at the highest UV-B intensities of
9 and 15 Wm(-2). Photosynthesis and the performance of photosystem II (PSII)
declined to similar extents in IE and NE plants following UV-B exposure,
suggesting that isoprene emission did not ameliorate the immediate impact of UV-B
on photosynthesis. However, after the stress, photosynthesis and PSII recovered
in IE plants, which maintained isoprene formation, but not in NE plants. Recovery
of IE plants was also associated with elevated antioxidant levels and cycling;
suggesting that both isoprene formation and antioxidant systems contributed to
reinstating the integrity and functionality of cellular membranes and
photosynthesis following exposure to excessive levels of UV-B radiation.
PMID- 25113454
TI - Overexpression of monoubiquitin improves photosynthesis in transgenic tobacco
plants following high temperature stress.
AB - The ubiquitin/26S proteasome system (Ub/26S) is implicated in abiotic stress
responses in plants. In this paper, transgenic tobacco plants overexpressing Ta
Ub2 from wheat were used to study the functions of Ub in the improvement of
photosynthesis under high temperature (45 degrees C) stress. We observed higher
levels of Ub conjugates in transgenic plants under high temperature stress
conditions compared to wild type (WT) as a result of the constitutive
overexpression of Ta-Ub2, suggesting increased protein degradation by the 26S
proteasome system under high temperature stress. Overexpressing Ub increased the
photosynthetic rate (Pn) of transgenic tobacco plants, consistent with the
improved ATPase activity in the thylakoid membrane and enhanced efficiency of
PSII photochemistry. The higher D1 protein levels following high temperature
stress in transgenic plants than WT were also observed. These findings imply that
Ub may be involved in tolerance of photosynthesis to high temperature stress in
plants. Compared with WT, the transgenic plants showed lower protein
carbonylation and malondialdehyde (MDA) levels, less reactive oxygen species
(ROS) accumulation, but higher antioxidant enzyme activity under high temperature
stress. These findings suggest that the improved antioxidant capacity of
transgenic plants may be one of the most important mechanisms underlying Ub
regulated high temperature tolerance.
PMID- 25113455
TI - Foliar CO2 in a holm oak forest subjected to 15 years of climate change
simulation.
AB - A long-term experimental drought to simulate future expected climatic conditions
for Mediterranean forests, a 15% decrease in soil moisture for the following
decades, was conducted in a holm oak forest since 1999. Net photosynthetic rate,
stomatal conductance and leaf water potential were measured from 1999 to 2013 in
Quercus ilex and Phillyrea latifolia, two co-dominant species of this forest.
These measurements were performed in four plots, two of them received the drought
treatment and the two other plots were control plots. The three studied variables
decreased with increases in VPD and decreases in soil moisture in both species,
but the decrease of leaf water potential during summer drought was larger in P.
latifolia, whereas Q. ilex reached higher net photosynthetic rates and stomatal
conductance values during rainy periods than P. latifolia. The drought treatment
decreased ca. 8% the net photosynthetic rates during the overall studied period
in both Q. ilex and P. latifolia, whereas there were just non-significant trends
toward a decrease in leaf water potential and stomatal conductance induced by
drought treatment. Future drier climate may lead to a decrease in the carbon
balance of Mediterranean species, and some shrub species well resistant to
drought could gain competitive advantage relative to Q. ilex, currently the
dominant species of this forest.
PMID- 25113456
TI - Opportunities for improving leaf water use efficiency under climate change
conditions.
AB - WUEi (intrinsic water use efficiency) is a complex (multi)-trait, that depends on
several physiological processes, driving plant productivity and its relation with
a changing environment. Climatic change predictions estimate increases in
temperature and drought in the semi-arid regions, rendering improved water use
efficiency is a mandatory objective to maintain the current global food supply.
The aims of this review were (i) to identify through a meta-analysis the leaf
traits mostly related to intrinsic water use efficiency (WUEi, the ratio between
A - net photosynthesis and gs - stomatal conductance), based on a newly compiled
dataset covering more than 200 species/varieties and 106 genus of C3 plants (ii)
to describe the main potential targets for WUEi improvement via biotechnological
manipulations and (iii) to introduce emergent and innovative technologies
including UAVs (Unmanned Aerial Vehicles) to scale up levels from leaf to whole
plant water status. We confirmed that increases in gm/gs and Vcmax/gs ratios are
systematically related with increases in WUEi maintained across species,
habitats, and environmental conditions. Other emergent opportunities to improve
WUEi are described such as the relationship between photosynthesis and
respiration and their link with metabolomics. Finally, we outline our hypothesis
that we are observing the advent of a "smart" agriculture, wherein new
technologies, such as UAVs equipped with remote sensors will rapidly facilitate
an efficient water use regulating the irrigation schedule and determination,
under field conditions, of cultivars with improved water use efficiency. We,
therefore, conclude that the multi-disciplinary challenge toward WUE has only
just begun.
PMID- 25113457
TI - Leaf respiration in darkness and in the light under pre-industrial, current and
elevated atmospheric CO2 concentrations.
AB - Our study sought to understand how past, low atmospheric CO2 concentrations
([CO2]) impact respiration (R) of soybean (Glycine max), when compared to plants
grown under current and future [CO2]s. Experiments were conducted using plants
grown under 290, 400 and 700 ppm [CO2]. Leaf R was measured in both darkness (RD)
and in the light (RL; using the Kok method), with short-term changes in
measurement [CO2] and [O2] being used to explore the relationship between light
inhibition of leaf R and photorespiration. Root R, photosynthesis (A), leaf [N]
and biomass allocation traits were also quantified. In contrast to the inhibitory
effect of low growth [CO2] on A, growth [CO2] had no significant effect on leaf
RD or root R. Irrespective of growth [CO2], RL was always lower than RD, with
light inhibiting leaf R by 17-47%. Importantly, the degree of light inhibition of
leaf R was lowest in plants grown under low [CO2], with variations in RL being
positively correlated with RD and photorespiration. Irrespective of whether leaf
R was measured in the light or dark, a greater proportion of the carbon fixed by
leaf photosynthesis was released by leaf R in plants grown under low [CO2] than
under current/future [CO2]'s. Collectively, our results highlight the
differential responses of A and R to growth of plants under low to elevated
atmospheric [CO2].
PMID- 25113458
TI - Limitations to soybean photosynthesis at elevated carbon dioxide in free-air
enrichment and open top chamber systems.
AB - It has been suggested that the stimulation of soybean photosynthesis by elevated
CO2 was less in free-air carbon dioxide enrichment (FACE) systems than in open
top chambers (OTC), which might explain smaller yield increases at elevated CO2
in FACE systems. However, this has not been tested using the same cultivars grown
in the same location. I tested whether soybean photosynthesis at high light and
elevated CO2 (ambient+180 MUmol mol(-1)) was limited by electron transport (J) in
FACE systems but by ribulose-bisphosphate carboxylation capacity (VCmax) in OTC.
FACE systems with daytime and continuous CO2 enrichment were also compared. The
results indicated that in both cultivars examined, midday photosynthesis at high
light was always limited by VCmax, both in the FACE and in the OTC systems.
Daytime only CO2 enrichment did not affect photosynthetic parameters or
limitations, but did result in significantly smaller yields in both cultivars
than continuous elevation. Photosynthesis measured at low photosynthetic photon
flux density (PPFD) was not higher at elevated than at ambient CO2, because of an
acclimation to elevated CO2 which was only evident at low measurement PPFDs.
PMID- 25113459
TI - Biochemical acclimation, stomatal limitation and precipitation patterns underlie
decreases in photosynthetic stimulation of soybean (Glycine max) at elevated
[CO2] and temperatures under fully open air field conditions.
AB - The net effect of elevated [CO2] and temperature on photosynthetic acclimation
and plant productivity is poorly resolved. We assessed the effects of canopy
warming and fully open air [CO2] enrichment on (1) the acclimation of two
biochemical parameters that frequently limit photosynthesis (A), the maximum
carboxylation capacity of Rubisco (Vc,max) and the maximum potential linear
electron flux through photosystem II (Jmax), (2) the associated responses of leaf
structural and chemical properties related to A, as well as (3) the stomatal
limitation (l) imposed on A, for soybean over two growing seasons in a
conventionally managed agricultural field in Illinois, USA. Acclimation to
elevated [CO2] was consistent over two growing seasons with respect to Vc,max and
Jmax. However, elevated temperature significantly decreased Jmax contributing to
lower photosynthetic stimulation by elevated CO2. Large seasonal differences in
precipitation altered soil moisture availability modulating the complex effects
of elevated temperature and CO2 on biochemical and structural properties related
to A. Elevated temperature also reduced the benefit of elevated [CO2] by
eliminating decreases in stomatal limitation at elevated [CO2]. These results
highlight the critical importance of considering multiple environmental factors
(i.e. temperature, moisture, [CO2]) when trying to predict plant productivity in
the context of climate change.
PMID- 25113460
TI - Impacts of rising tropospheric ozone on photosynthesis and metabolite levels on
field grown soybean.
AB - The response of leaf photosynthesis and metabolite profiles to ozone (O3)
exposure ranging from 37 to 116 ppb was investigated in two soybean cultivars
Dwight and IA3010 in the field under fully open-air conditions. Leaf
photosynthesis, total non-structural carbohydrates (TNC) and total free amino
acids (TAA) decreased linearly with increasing O3 levels in both cultivars with
average decrease of 7% for an increase in O3 levels by 10 ppb. Ozone interacted
with developmental stages and leaf ages, and caused higher damage at later
reproductive stages and in older leaves. Ozone affected yield mainly via
reduction of maximum rate of Rubisco carboxylation (Vcmax) and maximum rates of
electron transport (Jmax) as well as a shorter growing season due to earlier
onset of canopy senescence. For all parameters investigated the critical O3
levels (~50 ppb) for detectable damage fell within O3 levels that occur routinely
in soybean fields across the US and elsewhere in the world. Strong correlations
were observed in O3-induced changes among yield, photosynthesis, TNC, TAA and
many metabolites. The broad range of metabolites that showed O3 dose dependent
effect is consistent with multiple interaction loci and thus multiple targets for
improving the tolerance of soybean to O3.
PMID- 25113461
TI - Acclimation of photosynthetic tolerance to acute heat stress at elevated CO2 and
N.
AB - Determining interactive effects of pre-heat-stress, CO2 and N on photosynthetic
thermotolerance is necessary for predicting plant responses to global change. We
grew Hordeum vulgare (barley, C3) and Zea mays (corn, C4) at current or elevated
CO2 (370 and 700 ppm) and limiting or optimal soil N (0.5 and 7.5mM). We assessed
basal and inducible thermotolerance of net photosynthesis (Pn), photosystem II
efficiency [Formula: see text] , photochemical quenching (qp), carboxylation
efficiency (CE), and rubisco activase content. Inducible thermotolerance was
measured on plants which were pre-heat-stressed (PHS) for 4h before heat stress.
We also assayed content of several major heat-shock proteins (HSPs), as HSPs are
primary adaptations to heat stress and affected by N. Acclimation of
photosynthetic thermotolerance was dependent on species, CO2 and N treatment and
the component in the photosynthetic processes. PHS had a positive effect on the
production of HSP60 and sHSP in low-N barley and corn. These results indicate
that stimulatory effects of elevated CO2 at normal temperatures on photosynthesis
may be partly changed by the different interactive effects of CO2, heat stress
and N for species with different photosynthetic pathways. Thus, PHS, CO2 and N
effects on photosynthetic thermotolerance may contribute to changes in plant
productivity, distribution, and diversity.
PMID- 25113462
TI - Effects of elevated O3 exposure on seed yield, N concentration and photosynthesis
of nine soybean cultivars (Glycine max (L.) Merr.) in Northeast China.
AB - Nine soybean cultivars widely cultivated in Northeast China were investigated in
present study to assess their O3 sensitivities on the basis of the response of
photosynthesis and seed yield to ambient and future ozone (O3) concentrations,
and determine whether the effects of O3 vary with the developmental stages
(flowering and seed filling stages). Relative to charcoal-filtered air (CF),
elevated O3 concentration (E-O3, ambient air+40 ppb) significantly reduced
soybean yields by 40%, with a range of 32-46% among cultivars. E-O3 also induced
significant decreases in pigment contents, net photosynthetic rate and
chlorophyll a fluorescence at both flowering and seed filling stages in most
cultivars. Except net photosynthetic rate and stomatal conductance (gs) at seed
filling stage, all variables showed no significant interaction between O3 and
cultivar, suggesting that all tested cultivars had similar sensitivities to O3.
The responses of seed N content to E-O3 differed among cultivars. Ambient O3
concentration (mean of daily concentration of 19 ppb) did not induce any change
relative to CF. Significant positive relationship between endogenous gs in CF and
yield loss among cultivars was found only at seed filling stage. Positive
correlation between effects of E-O3 on leaf N content and effects on light
saturated photosynthetic rate (Asat) indicated that gs and leaf N content at seed
filling stage contributes to yield loss and decreased photosynthesis by E-O3,
respectively. It can be inferred that E-O3 had a larger negative effects on seed
filling stage than flowering stage of soybean.
PMID- 25113463
TI - Impacts of elevated ozone on growth and photosynthesis of Metasequoia
glyptostroboides Hu et Cheng.
AB - One-year-old Metasequoia glyptostroboides seedlings were exposed to non-filtered
ambient air (NF) and elevated ozone (E-O3, NF+60 ppb) in open-top chambers for
two years. E-O3 accelerated leaf senescence, as indicated by significant
decreases in photosynthetic pigment contents with the elongation of O3 exposure.
E-O3 significantly affected gas exchange and carboxylation, inducing reductions
in light-saturated photosynthesis (Asat), the maximum activity of Rubisco
(Vc,max) and the maximum electron transport rate (Jmax). Chl a/b, Vc,max/Jmax and
stomatal limitation (l) were not affected. Stomatal conductance (gs) was
significantly decreased by E-O3 in the first year, but remained unchanged in the
second year. It can be inferred that the decrease in Asat by E-O3 was mainly
attributed to the changes in non-stomatal factors. After two years' exposure, E
O3 caused significant decreases in canopy photosynthesis and leaf mass per area,
and a significant increase in the number of branches, but induced slight, not
significant decreases in growth and biomass. Therefore, it can be concluded that
the carbon accumulation of the species M. glyptostroboides could be negatively
affected after long-term exposure to high O3 concentration.
PMID- 25113465
TI - Transcriptional networks leading to symbiotic nodule organogenesis.
AB - The symbiosis with nitrogen-fixing bacteria leading to root nodules is a
relatively recent evolutionary innovation and limited to a distinct order of land
plants. It has long been a mystery how plants have invented this complex trait.
However, recent advances in molecular genetics of model legumes has elucidated
genes involved in the development of root nodules, providing insights into this
process. Here we discuss how the de novo assembly of transcriptional networks may
account for the predisposition to nodulate. Transcriptional networks and modes of
gene regulation from the arbuscular mycorrhizal symbiosis, nitrate responses and
aspects of lateral root development have likely all contributed to the emergence
and development of root nodules.
PMID- 25113466
TI - Au nanoparticle sensitized ZnO nanopencil arrays for photoelectrochemical water
splitting.
AB - This paper describes the synthesis of Au nanoparticle sensitized ZnO nanopencil
arrays on F-doped SnO2 substrates by an aqueous chemical growth and subsequent
photoreduction method. The Au-ZnO nanopencil arrays yield a photocurrent of ~ 1.5
mA cm(-2) at 1 V versus Ag/AgCl. The enhanced photocurrent is attributed to the
surface plasmon resonance effect of Au nanoparticles and the prolonged lifetime
of the photo-generated electron-hole pairs. The improved stability of ZnO is due
to the plasmon resonance energy transfer process enabled by the Au nanoparticles,
which enhances the electric field intensity in a small, well-defined location of
the ZnO semiconductor.
PMID- 25113467
TI - Revision of Siobla (Hymenoptera, Tenthredinidae) from Japan.
AB - The Japanese species of the sawfly genus Siobla Cameron, 1877, are revised and
keyed. The following nine species are recognized: S. apicalis Takeuchi, 1929, S.
ferox (Smith, 1874), S. hirasana Takeuchi, 1929, S. jucunda (Mocsary, 1909), S.
metallica Takeuchi, 1929, S. sturmii (Klug, 1817), S. japonica, sp. nov., S.
pulchra, sp. nov., and S. takeuchii, sp. nov. Siobla pacifica (Smith, 1874) is
synonymized with S. sturmii. Lectotypes are designated for Macrophya ferox Smith,
1874, Macrophya pacifica Smith, 1874, Encarsioneura jucunda Mocsary, 1909, and
Siobla grandis Matsumura, 1912. Previous records of S. ruficornis (Gimmerthal,
1834) and S. villosa Malaise, 1931, from Japan have been found erroneous. Siobla
jucunda is newly recorded from Japan.
PMID- 25113468
TI - Revision of the Siobla formosana group (Hymenoptera: Tenthredinidae).
AB - 14 species of the Siobla formosana species-group are revised. Three new species:
Siobla jiangi Niu & Wei, sp. nov., S. parallela Niu & Wei, sp. nov., S. weiweii
Niu & Wei, sp. nov. are described. Siobla rufipes Malaise, 1945 is a new synonym
of S. atra Malaise, 1945. The males formerly assigned to S. atra belong to S.
semipicta Malaise, 1945. The previously unknown female of Siobla rufopropodea
Wei, 1998 is described. Lectotypes are designated for Siobla rufipes Malaise,
1945, Siobla atra Malaise, 1945 and Siobla semipicta Malaise, 1945. The
previously described species are illustrated and partly redescribed. A key to
species of the group is given. Distribution records of each species of the group
except S. takeuchii are given.
PMID- 25113470
TI - A checklist of the Kateretidae and Nitidulidae of Iran (Coleoptera: Cucujoidea).
AB - The current knowledge of the geographic distribution of short-winged flower
beetles and sap beetles (Kateretidae and Nitidulidae, respectively) from Iran is
summarized. In total, 84 species of Nitidulidae (in 22 genera and 5 subfamilies:
Epuraeinae, Carpophilinae, Cryptarchinae, Nitidulinae, Meligethinae) and 6
species of Kateretidae (in 4 genera: Brachyleptus Motschulsky, Brachypterolus
Grouvelle, Brachypterus Kugelann, Kateretes Herbst) are listed. Brachyleptus
discolor Reitter, Brachypterus glaber (Newman) (both Kateretidae), Epuraea
distincta (Grimmer), Soronia oblonga (Brisout), Lamiogethes bidens (Brisout),
Lamiogethes medvedevi (Kirejtshuk), Sagittogethes devillei (Grouvelle) and
Xerogethes rotundicollis (Brisout) (Nitidulidae) are new records for Iran.
PMID- 25113469
TI - Review of the Eulamprotes wilkella species-group based on morphology and DNA
barcodes, with descriptions of new taxa (Lepidoptera, Gelechiidae).
AB - The Eulamprotes wilkella species-group is revised based on morphological
characters and on DNA barcodes of the mtCOI (Cytochrome c Oxidase 1) gene. Adult
morphology combined with sequence information for 9 species supports the
existence of 12 species, 7 of which are described as new to science: E. mirusella
Huemer & Karsholt sp. nov. (France), E. baldizzonei Karsholt & Huemer sp. nov.
(Italy, Slovenia, Croatia), E. atrifrontella Karsholt & Huemer sp. nov. (Turkey),
E. wieseri Huemer & Karsholt sp. nov. (Kyrgizia), E. altaicella Huemer & Karsholt
sp. nov. (Russia: Altai, Buryatia, Tuva Republic), E. kailai Karsholt & Huemer
sp. nov. (Kazakhstan, Kyrgizia, Russia: Buryatia, Tuva Republic) and E.
gemerensis Elsner sp. nov. (Slovakia). E. buvati Leraut, 1991 syn. nov. is
synonymized with E. ochricapilla (Rebel, 1903).
PMID- 25113471
TI - A cryptic new species of Miniopterus from south-eastern Africa based on molecular
and morphological characters.
AB - Resolving species limits within the genus Miniopterus has traditionally been
complicated by the presence of cryptic species with overlapping morphological
features. We use molecular techniques, cranio-dental characters and tragus shape
to describe a new species of Miniopterus from Mozambique, M. mossambicus.
Miniopterus mossambicus shows > 12% divergence in cytochrome-b sequence from its
nearest congeners (the Malagasy M. gleni and M. griveaudi) and > 15% divergence
from the morphologically similar M. natalensis, M. fraterculus and M. minor (all
of which occur in southern and eastern Africa). There is considerable overlap in
cranio-dental characters of the southern African species, particularly M.
natalensis and M. mossambicus. However, tragus shape and multivariate comparisons
of skull measurements can be used to separate these species. Based on
morphological comparisons of museum specimens, this species may also be present
in neighbouring Malawi and Zimbabwe, suggesting that it is probably distributed
widely in south-central Africa.
PMID- 25113472
TI - Review of the genus Cidariplura Butler, 1879 (Lepidoptera, Erebidae, Herminiinae)
in Taiwan with descriptions of four new species.
AB - The genus Cidariplura Butler, 1879 from Taiwan is reviewed. A total of seven
species are confirmed to occur in this old landbridge island, and four new
species are described: C. shanmeii Wu & Owada sp. nov., C. maraho Wu & Owada sp.
nov., C. atayal Wu & Owada sp. nov. and C. ilana Wu & Owada sp. nov. The
Taiwanese C. bilineata (Wileman & South, 1919) is superficially similar to the
Indian and Nepalese C. brevivittalis (Moore, 1867) but their genitalia show
distinct differences. Elyra albifascia Hampson 1929 is regarded as a junior
synonym of C. brevivittalis (syn. nov.). All diagnostic characteristics of
Cidariplura from Taiwan and its adjacent areas are illustrated.
PMID- 25113473
TI - New records of Recent Brachiopoda from the Red Sea with a description of a new
species .
AB - A revised checklist of 14 Recent brachiopod species from Egypt and the Sudan in
the Red Sea has been compiled. New records of Minutella minuta (Cooper),
Thecidellina blochmanni Dall and Argyrotheca somaliensis Cooper are described and
a new species Argyrotheca cooperi is erected for specimens with few but very
strong costae. The new records support earlier suggestions that the affinities of
the Red Sea brachiopod fauna are with those of the Mediterranean and Indo-Pacific
areas.
PMID- 25113474
TI - A new species of fiddler crab from the Ogasawara (Bonin) Islands, Japan,
separated from the widely-distributed sister species Uca (Paraleptuca) crassipes
(White, 1847) (Crustacea: Decapoda: Brachyura: Ocypodidae).
AB - A new species of fiddler crab (Brachyura: Ocypodidae), Uca boninensis sp. nov.,
is described from the Ogasawara (Bonin) Islands, Japan. The new species has
previously been identified with the widely distributed U. crassipes (White,
1847), from which it differs by having a slightly differently shaped carapace,
and relatively stouter male first gonopods (G1). The recognition of the new
species is also supported by differences in the mitochondrial cytochrome oxidase
I (COI) and control region (CR) genes. U. boninensis sp. nov., appears to be
endemic to the Ogasawara Islands, and as the only known population is small,
urgent conservation measures are needed for its protection. Our study brings the
total number of the Japanese fiddler crab species to 12.
PMID- 25113475
TI - A new form of Elongatoolithidae, Undulatoolithus pengi oogen. et oosp. nov. from
Pingxiang, Jiangxi, China.
AB - A new oogenus and oospecies of the Elongatoolithidae, Undulatoolithus pengi
oogen. et oosp. nov., is described on the basis of specimens from the Upper
Cretaceous Zhoutian Formation of the Pingxiang Basin, Jiangxi Province, China.
The eggs are slightly asymmetrical, paired, and lay radially-oriented in a
circular configuration within the clutch, and most suggestive of Macroolithus of
the Elongatoolithidae by medium-sized eggs with average polar axis and equatorial
diameter of 19.36 and 8.35 cm, and the ornamentation pattern of nodes and ridges
on the outer surface. The new oogenus differs from Macroolithus in its prominent
ridges 0.67 mm in height, about half of the entire eggshell thickness,
gradational boundary between the cone layer and the overlying columnar layer,
cone layer-to-columnar layer thickness ratio of 1/8 or 1/4. This discovery adds
new data on the morphology and diversification of Late Cretaceous elongatoolithid
ootaxa.
PMID- 25113476
TI - A new dasyurid marsupial from Kroombit Tops, south-east Queensland, Australia:
the Silver-headed Antechinus, Antechinus argentus sp. nov. (Marsupialia:
Dasyuridae).
AB - Antechinus argentus sp. nov. is currently only known from the plateau at the
eastern escarpment of Kroombit Tops National Park, about 400km NNW of Brisbane
and 60km SSW of Gladstone, south-east Queensland, Australia. Antechinus flavipes
(Waterhouse) is also known from Kroombit Tops NP, 4.5km W of the nearest known
population of A. argentus; A. mysticus Baker, Mutton and Van Dyck has yet to be
found within Kroombit Tops, but is known from museum specimens taken at Bulburin
NP, just 40km ESE, as well as extant populations about 400km to both the south
east and north-west of Kroombit NP. A. argentus can be easily distinguished in
the field, having an overall silvery/grey appearance with much paler silver feet
and drabber deep greyish-olive rump than A. flavipes, which has distinctive
yellow-orange toned feet, rump and tail-base; A. argentus fur is also less coarse
than that of A. flavipes. A. argentus has a striking silver-grey head, neck and
shoulders, with pale, slightly broken eye-rings, which distinguish it from A.
mysticus which has a more subtle greyish-brown head, pale buff dabs of eyeliner
and more colourful brownish-yellow rump. Features of the dentary can also be used
for identification: A. argentus differs from A. flavipes in having smaller molar
teeth, as well as a narrower and smaller skull and from A. mysticus in having on
average a narrower snout, smaller skull and dentary lengths and smaller posterior
palatal vacuities in the skull. A. argentus is strongly divergent genetically (at
mtDNA) from both A. flavipes (9.0-11.2%) and A. mysticus (7.2-7.5%), and forms a
very strongly supported clade to the exclusion of all other antechinus species,
in both mtDNA and combined (mtDNA and nDNA) phylogenies inferred here. We are yet
to make detailed surveys in search of A. argentus from forested areas to the
immediate east and north of Kroombit Tops. However, A. mysticus has only been
found at these sites in low densities in decades past and not at all in several
recent trapping expeditions conducted by the authors. With similar habitat types
in close geographic proximity, it is plausible that A. argentus may be found
outside Kroombit. Nevertheless, it is striking that from a range of surveys
conducted at Kroombit Tops in the last 15 years and intensive surveys by the
authors in the last 3 years, totalling more than 5 080 trap nights, just 13 A.
argentus have been captured from two sites less than 6 km apart. If this is even
close to the true geographic extent of the species, it would possess one of the
smallest distributions of an Australian mammal species. With several threats
identified, we tentatively recommend that A. argentus be listed as Endangered,
pending an exhaustive trapping survey of Kroombit and surrounds.
PMID- 25113477
TI - Revision of the genus Ortopla Walker, [1859] with description of two new species
from Southeast Asia (Lepidoptera, Noctuidae, Pantheinae). Revision of Pantheinae,
contribution X.
AB - The pantheine genus Ortopla Walker, [1859] 1858 is revised. Two new species,
Ortopla witti sp. n. from the Philippines and O. longiuncus sp. n. from Nepal,
Vietnam, Thailand, Myanmar and South China are described. The name O. commutanda
Warren, 1891 (syn. n.) is synonymised with O. iarbasalis Walker, [1859] 1858. The
distribution of species in East Asia is clarified. A checklist of the genus
Ortopla is presented. Imagines, male and female genitalia of all species are
illustrated.
PMID- 25113478
TI - Review and revision of Australian Germalus Stal, with new genera and further new
species of Australian Geocorinae (Hemiptera: Heteroptera: Geocoridae).
AB - During a review of Australian Germalus Stal, types of all species recorded from
Australia, as well as of the type species G. kinbergi Stal, originally described
from Mauritius Island, were examined and illustrated to redefine and redescribe
the genus as well as all the included species. As a result of this, the following
synonymies have become necessary: G. humeralis Distant as junior synonym of G.
victoriae Bergroth; G. roseobistriatus Kirkaldy as junior synonym of G.
lineolosus Distant. Lectotype females have been designated for Germalus victoriae
Bergroth, and Germalus lineolosus Distant. The following new taxa have been
discovered in the material available for this study: Germalus australis Malipatil
sp. nov., Germalus fuscovittatus Malipatil sp. nov., Germalus littoralis
Malipatil sp. nov., Capitostylus kurandae Malipatil gen. et sp. nov.,
Unicageocoris griseus Malipatil gen. et sp. nov., and Ausogeocoris westraliensis
Malipatil gen. et sp. nov. Keys to the six genera of Geocorinae, and to the six
species of Germalus, now recognised in Australia, are provided.
PMID- 25113479
TI - Revised world catalogue of Eucopina, Eucosma, Pelochrista, and Phaneta
(Lepidoptera: Tortricidae: Eucosmini).
AB - A revised world catalogue of Eucopina, Eucosma, Pelochrista, and Phaneta is
provided. Assignment to genus is based on generic redescriptions by Gilligan et
al. (2013). A total of 709 names (including subspecies and synonyms) are listed,
including 251 new combinations and 52 revised combinations.
PMID- 25113480
TI - Four new species of Noeetomima Enderlein (Diptera: Lauxaniidae), with a key to
world species.
AB - The following four species are described as new to science: Noeetomima chinensis
sp. nov. (China), N. jinpingensis sp. nov. (China, Nepal), N. tengchongica sp.
nov. (China) and N. yunnanica sp. nov. (China). The species Noeetomima aberrans
Shatalkin and N. nepalensis Stuckenberg are newly recorded for Japan and India,
respectively, and the male genitalia for N. thaiensis Sasakawa are described and
illustrated for the first time. A key to separate world species is presented, as
is a detailed checklist of all species.
PMID- 25113481
TI - Phytoseiid mites (Acari) associated with yerba mate in southern Brazil, with
description of a new species.
AB - Yerba mate is a plant of great socioeconomic importance in southern South
America. Little has been published about the phytoseiid mite fauna of yerba mate.
This paper presents information about the morphology and distribution of
phytoseiid mites collected in yerba mate in the Ilopolis and Putinga counties of
Brazil between 2002 and 2004. Four areas with of different forms of cultivation
in every county were sampled. A list of the species recorded from that state, and
a key for their identification are provided. Sixteen phytoseiid mites species
were identified, belonging to 11 genera in the subfamilies Amblyseiinae (13
species) and Typhlodrominae (three species). The most abundant genus was
Amblyseius with three species. Phytoscutus sexpilis Muma, 1961 and Typhloseiopsis
dorsoreticulatus Lofego, Demite & Feres, 2011 are reported for the first time
from Rio Grande do Sul state. This study also includes the description of a new
species, Typhlodromips pallinii n. sp.
PMID- 25113482
TI - Timoides agassizii Bigelow, 1904, little-known hydromedusa (Cnidaria), appears
briefly in large numbers off Oman, March 2011, with additional notes about
species of the genus Timoides.
AB - A bloom of the hydromedusan jellyfish, Timoides agassizii, occurred in February
2011 off the coast of Sohar, Al Batinah, Sultanate of Oman, in the Gulf of Oman.
This species was first observed in 1902 in great numbers off Haddummati Atoll in
the Maldive Islands in the Indian Ocean and has rarely been seen since. The
species appeared briefly in large numbers off Oman in 2011 and subsequent
observation of our 2009 samples of zooplankton from Sohar revealed that it was
also present in low numbers (two collected) in one sample in 2009; these are the
first records in the Indian Ocean north of the Maldives. Medusae collected off
Oman were almost identical to those recorded previously from the Maldive Islands,
Papua New Guinea, the Marshall Islands, Guam, the South China Sea, and Okinawa.
T. agassizii is a species that likely lives for several months. It was present in
our plankton samples together with large numbers of the oceanic siphonophore
Physalia physalis only during a single month's samples, suggesting that the
temporary bloom off Oman was likely due to the arrival of mature, open ocean
medusae into nearshore waters. We see no evidence that T. agassizii has
established a new population along Oman, since if so, it would likely have been
present in more than one sample period. We are unable to deduce further details
of the life cycle of this species from blooms of many mature individuals
nearshore, about a century apart. Examination of a single damaged T. agassizii
medusa from Guam, calls into question the existence of its congener, T.
latistyla, known only from a single specimen.
PMID- 25113484
TI - First record of the bee genus Homalictus Cockerell for China with description of
a new species (Hymenoptera: Halictidae: Halictini).
AB - This paper reports the first record of the genus Homalictus from China. We
describe and illustrate H. (H.) nabanensis sp. n. collected from the Naban River
Watershed National Nature Reserve, Xishuangbanna, Yunnan, China. The type
specimens are deposited in Institute of Zoology, Chinese Academy of Sciences,
Beijing, China.
PMID- 25113483
TI - New bioacoustic and distributional data on Bokermannohyla sapiranga Brandao et
al., 2012 (Anura: Hylidae): revisiting its diagnosis in comparison with B.
pseudopseudis (Miranda-Ribeiro, 1937).
AB - In this paper, we provide new bioacoustic and distributional data on
Bokermannohyla sapiranga, as well as additional comparative bioacoustic data on
topotypes of B. pseudopseudis, and re-evaluate the differential diagnosis of the
former species with respect to the latter. Head shapes (dorsal and lateral views)
presented such variation that should not be used to differentially diagnose them
as originally proposed. On the other hand, the presence of a dermal ridge along
outer tarsi, and color patterns of the eyes and dorsal surface of hand/toe disks
still represent diagnostic characters between both species. We also found
differences in temporal (call duration; notes per call), spectral (dominant
frequency; harmonics), and structural (pulsed/non-pulsed note structure) traits
of their calls. Distribution of B. sapiranga is extended eastward (Paracatu),
which corresponds to the first record for the State of Minas Gerais, whereas B.
pseudopseudis distribution seems to be restricted to rocky montane field
environments of northern Goias State.
PMID- 25113485
TI - An integrative appraisal of the diagnosis and distribution of Allobates sumtuosus
(Morales, 2002) (Anura, Aromobatidae).
AB - We describe the advertisement calls and color in life of Allobates sumtuosus
(Morales 2002) based on specimens recorded and collected at its type locality in
Reserva Biologica do Rio Trombetas, Brazilian Amazonia. We also improve the
species diagnosis by adding information on states of characters frequently used
in current Allobates taxonomy. Finally, we analyze genetic distances and the
evolutionary relationships between typical A. sumtuosus and other Allobates
species distributed in Brazil and along the Guiana Shield region using a fragment
of the 16S rDNA mitochondrial gene. Based on this integrative analysis, we
propose the synonym of Allobates spumaponens Kok & Ernst 2007 with A. sumtuosus
and provide an updated geographic distribution of the species.
PMID- 25113486
TI - Revision of the Old World genera Panthea Hubner, [1820] 1816 and Pantheana
Hreblay, 1998 with description two new species from China (Lepidoptera,
Noctuidae: Pantheinae). Revision of Pantheinae, contribution IX.
AB - The Old World species of the genus Panthea Hubner [1820] 1816 are revised. The
article contains the description of two new species Panthea fuscogrisea sp. n.
and Panthea florianii sp. n. from continental China and re-description of two
species P. roberti Joannis 1928 and P. grisea Wileman, 1919 with illustration of
male and female genitalia. Diphthera hoenei Draudt, 1950 (syn. n.) is synonymised
with P. roberti Joannis 1928. The species Panthea ronnyi Thony, 1996 is excluded
from the genus Panthea. Lectotypes for Diphthera hoenei and Panthea roberti are
designated. The genus includes five species in the Old World, distributed mainly
in Sino-Himalayan subregion of the Palaearctic. A checklist of species of the
genus Panthea is presented. The little-known genus Pantheana Hreblay, 1998 with
the sole species Pantheana yangzisherpana Hreblay, 1998 is reviewed. The
imagines, male and female genitalia of all Old World species of Panthea and
Pantheana are illustrated.
PMID- 25113488
TI - A new species of water mite (Acari, Hydrachnidia) from Assam, India, found in the
gut contents of the fish Botia dario (Botiidae).
AB - Water mites (Hydrachnidia) occur sporadically in the gut of freshwater fishes. In
this study, nine water mite items were found in the gut contents of the fish
Botia dario (Hamilton, 1822) (Botiidae) collected in a floodplain wetland (beel)
in the river island Majuli, Assam, India. Torrenticola episce is described as new
to science; Torrenticola haliki Pesic & Smit 2010, Monatractides oxystomus (K.
Viets, 1935) and Hygrobates cf. sinensis Uchida & Imamura, 1951, are reported for
the first time from India.
PMID- 25113487
TI - The "Rhampholeon uluguruensis complex" (Squamata: Chamaeleonidae) and the
taxonomic status of the pygmy chameleons in Tanzania.
AB - The specific status of several pygmy chameleons endemic to mountain massifs in
the Eastern Arc Mountains, Tanzania has long been controversial due to their lack
of distinctive morphological characters. In this work we extend our previous
sampling of Rieppeleon and Rhampholeon species, especially from the Rhampoleon
moyeri/Rhampholeon uluguruensis complex, and add data from a new mitochondrial
marker to address this problem. Our results show that there is geographical
structure between populations of pygmy chameleons from different mountains. This
structure is especially well defined for Rhampholeon (Rhinodigitum). Phylogenetic
analyses confirm that both Rh. uluguruensis Tilbury and Emmrich, 1995 and Rh.
moyeri Menegon, Salvidio and Tilbury, 2002 are distinct lineages, the former from
the Uluguru Mountains and the latter from the Udzungwa Mountains. However, the
paratype material used to erect Rh. moyeri belongs to a separate lineage from the
holotype. Similarly, a number of additional lineages within the Rh. moyeri/Rh.
uluguruensis complex recovered in the analysis may deserve specific status. At
present, there is a lack of morphological characters that can be used to
distinguish these lineages, suggesting that there are multiple cryptic taxa in
this complex.
PMID- 25113489
TI - A new species of karst-adapted Cnemaspis Strauch, 1887 (Squamata: Gekkonidae)
from a threatened karst region in Pahang, Peninsular Malaysia.
AB - A new species of karst-adapted gekkonid lizard of the genus Cnemaspis Strauch is
described from Gua Gunting and Gua Goyang in a karst region of Merapoh, Pahang,
Peninsular Malaysia whose unique limestone formations are in immediate danger of
being quarried. The new species differs from all other species of Cnemaspis based
on its unique suite of morphological and color pattern characters. Its discovery
underscores the unique biodiversity endemic to karst regions and adds to a
growing list of karst-adapted reptiles from Peninsular Malaysia. We posit that
new karst-adapted species endemic to limestone forests will continue to be
discovered and these regions will harbor a significant percentage of Peninsular
Malaysia's biodiversity and thusly should be conserved rather than quarried.
PMID- 25113490
TI - New and little known species of Nemouridae (Plecoptera) from Inner Mongolia of
China.
AB - Four species of the family Nemouridae, Amphinemura helanshana sp. n., A. didyma
Zhu & Yang, Nemoura geei Wu, and Nemoura cf. securigera Klapalek were collected
during a two years survey of the Helan Mountains of Inner Mongolia, China.
Nemoura cf. securigera has not been collected for more than one hundred years.
PMID- 25113491
TI - Two new species of the leafhopper genus Anidiocerus (Hemiptera: Cicadellidae:
Idiocerinae) from China.
AB - Two new species of Anidiocerus from China, A. brevispinus Xue & Zhang sp. nov.
and A. longimus Xue & Zhang sp. nov. are described and illustrated, and A.
variabilis Maldonado-Capriles, 1976 is placed as a senior synonym of A. flavidus
Cai & Shen, 1998, syn. nov. A redescription of the genus is provided together
with a checklist and key for the separation of males.
PMID- 25113492
TI - Heleodromia Haliday newly found in Tibet with description of one new species
(Diptera: Empidoidea: Trichopezinae).
AB - Heleodromia Haliday is recorded from Tibet for the first time with the following
three species belonging to the subgenus Heleodromia: Heleodromia (Heleodromia)
ausobskyi Wagner, Heleodromia (Heleodromia) basiflava sp. nov. and H. (H.)
immaculata Haliday. This finding extends the distribution of Heleodromia in China
from Northwest China to Southwest China. A key to the known species of
Heleodromia from the Himalayas is presented.
PMID- 25113493
TI - The male and larvae of Nigritothrips longistylosus (Thysanoptera, Thripidae) with
observations on its biology.
AB - The male and larvae of Nigritothrips longistylosus (Priesner) are described for
the first time. The life cycle, seasonal abundance, natural enemies and host
plant relationships are described. This is the first record of this species from
the Iberian Peninsula.
PMID- 25113494
TI - Thailand Agromyzidae (Diptera)-2.
AB - The 29 species of the subfamily Agromyzinae in Thailand are revised, among these
13 species are described as new to science: Melanagromyza ancyla sp. nov., M.
catalexis sp. nov., M. cirrappendicula sp. nov., M. lunulata sp. nov., M.
macilenta sp. nov., M. multistriata sp. nov., M. pandiculata sp. nov., M.
sexseriata sp. nov., M. spinuliloba sp. nov., M. turgida sp. nov., Ophiomyia
flagellata sp. nov., O. quadrifida sp. nov., O. striata sp. nov.; and nine
species (three species of Agromyza, two of Melanagromyza and four of Ophiomyia)
are recorded as new to Thailand. One new synonym is established: Melanagromyza
cordiophoeta Spencer, 1961, as a junior synonym of M. dolichostigma Meijere,
1922. Keys to the Thailand species of the genera Agromyza, Melanagromyza and
Ophiomyia are given.
PMID- 25113495
TI - Calappid and leucosiid crabs (Crustacea: Decapoda: Brachyura) from Kerala, India,
with the description of a new species of Mursia Desmarest, 1823, from the Arabian
Sea and redescription of M. bicristimana Alcock & Anderson, 1894.
AB - Eleven species of calappid and leucosiid crabs were identified from by-catch
landed by trawlers at four fishing ports in Kerala, India that were surveyed in
2007 and supplemented by material obtained in January 2013. Four species are
reported for the first time from India, six are new records for Kerala. The
status of Mursia bicristimana Alcock & Anderson, 1894, is clarified and the
species redescribed. A new species of Mursia is described from the Gulf of Aden,
Arabian Sea.
PMID- 25113496
TI - Taxonomic study of Bathygadidae fishes (Gadiformes) from Atlantic Spanish waters
combining morphological and molecular approaches.
AB - From 2009 to 2011 eleven specimens belonging to four bathygadid species of the
family Bathygadidae were captured in two different locations in the northern
waters of Spain. The morphometric measurements and meristic characters of these
specimens are given. The specimens were identified as belonging to the genera
Gadomus Regan, 1903, and Bathygadus Gunther, 1878, including the following
species: Gadomus dispar (Vaillant, 1888), Gadomus longifilis (Goode & Bean,
1885), Gadomus arcuatus (Goode & Bean, 1886) and Bathygadus melanobranchus
Vaillant, 1888. As a result, a new northern limit of distribution of G. arcuatus
from the northeastern Atlantic is reported. The first molecular identification
and genetic interrelationships of Bathygadidae species, based on the
mitochondrial COI nucleotide sequences -DNA barcodes- is reported. Sequences
corresponding to specimens from the same species were identical and the overall
mean genetic diversity (uncorrected p-distance) was 0.096 +/- 0.008. Based on a
morphological and meristic examination of the specimens, as well as on the
available literature, an updated key of the members of the family Bathygadidae
from the north-eastern Atlantic Ocean is provided.
PMID- 25113497
TI - A new species of Murina (Mammalia: Chiroptera: Vespertilionidae) from peninsular
Thailand.
AB - A new species of Murina belonging to 'suilla-group' is described based on two
specimens collected with harp traps in lowland evergreen forest in the
southernmost part of peninsular Thailand. Morphology and molecular (mitochondrial
COI) data suggest that the new species is most closely related to M. eleryi,
which is currently known from Indochina. The new species, however, can be
distinguished by the size and shape of the upper canine, the shape of the upper
and lower premolars, and the colour of the ventral pelage. Additional data on
bacular morphology, echolocation, ecology, and distribution are included.
PMID- 25113498
TI - The identity of the genus Scatocoenosia Schnabl, 1915 (Diptera: Muscidae).
AB - A re-description is given of the problematic genus and species Scatocoenosia
cordyluraeformis Schnabl, 1915. Illustrations of the male and female terminalia,
and images of the female holotype and the male of this species, are given. The
syno-nymy of Scatocoenosia Schnabl, 1915 with Spilogona Schnabl, 1911 is
confirmed, and notes are given on the relationships of S. cordyluraeformis with
other Spilogona species.
PMID- 25113499
TI - Description of the male genitalia of Belminus rugulosus Stal and Belminus
corredori Galvao & Angulo, and comments on the holotype of Parabelminus yurupucu
Lent & Wygodzinsky (Hemiptera: Heteroptera: Reduviidae: Triatominae:
Bolboderini).
AB - The male genitalia of Belminus rugulosus Stal and Belminus corredori Galvao &
Angulo are described and illustrated for the first time. Comments on the holotype
of Parabelminus yurupucu Lent & Wygodzinsky are presented (Hemiptera:
Heteroptera: Reduviidae: Triatominae: Bolboderini). A discussion on previous data
in the literature on male genitalia of species of Belminus Stal is provided.
PMID- 25113500
TI - The genus Orestias (Teleostei: Cyprinodontidae): nomenclatural errors in the
assignation of species names.
PMID- 25113504
TI - The biosafety of lanthanide upconversion nanomaterials.
AB - Lanthanide upconversion nanophosphors (UCNPs) show unique upconversion
luminescence where lower-energy photons (such as near-infrared (NIR) excitation)
are converted into higher-energy photons covering the NIR to the UV region, and
are considered to have a bright future in clinical translation. As UCNPs are used
in a significant number of potential bio-applications, their biosafety is
important and has attracted significant attention. In this critical review,
recent reports regarding the cellular internalization, biodistribution,
excretion, cytotoxicity and in vivo toxic effects of UCNPs are reviewed. In
particular, the studies which evaluated the association between the chemical and
physical properties of UCNPs and their biodistribution, excretion, and toxic
effects are presented in detail. Finally, we also discuss the challenges of
ensuring the biosafety of UCNPs in vivo.
PMID- 25113502
TI - Fair and unfair punishers coexist in the Ultimatum Game.
AB - In the Ultimatum Game, a proposer suggests how to split a sum of money with a
responder. If the responder rejects the proposal, both players get nothing.
Rejection of unfair offers is regarded as a form of punishment implemented by
fair-minded individuals, who are willing to impose the cooperation norm at a
personal cost. However, recent research using other experimental frameworks has
observed non-negligible levels of antisocial punishment by competitive, spiteful
individuals, which can eventually undermine cooperation. Using two large-scale
experiments, this note explores the nature of Ultimatum Game punishers by
analyzing their behavior in a Dictator Game. In both studies, the coexistence of
two entirely different sub-populations is confirmed: prosocial punishers on the
one hand, who behave fairly as dictators, and spiteful (antisocial) punishers on
the other, who are totally unfair. The finding has important implications
regarding the evolution of cooperation and the behavioral underpinnings of stable
social systems.
PMID- 25113503
TI - [Abdominal pain and ascites formation in a 72-year-old woman].
AB - A 72-year-old woman presented with abdominal pain after micturition. Abdominal
ultrasound screening revealed ascites associated with acute renal failure.
Paracentesis of the peritoneal fluid was performed. Biochemical analysis
indicated a peritoneal transsudate and increased creatinine. Cystoscopy detected
a rupture of the urinary bladder. Catheterization and antibiotic therapy resulted
in an improvement of pain and closure of the hole in the urinary bladder wall.
Several different disorders can induce a rupture of the urinary bladder. In this
case, severe chronic constipation was the most probable causative disease.
PMID- 25113505
TI - Solitary fibrous tumors of the pleura with Doege-Potter syndrome: a case report
and three-decade review of the literature.
AB - BACKGROUND: No case of solitary fibrous tumor of the pleura with Doege-Potter
syndrome has been reported in China. This study was to report a rare repeatedly
recurrent case of solitary fibrous tumor of the pleura with Doege-Potter syndrome
diagnosed in China and a three-decade literature review of solitary fibrous tumor
of the pleura with Doege-Potter syndrome worldwide. CASE PRESENTATION: A rare
case of solitary fibrous tumor of the pleura with Doege-Potter syndrome was
diagnosed in 2005 with follow-up to 2011. All medical records were collected and
literature of solitary fibrous tumor of the pleura with Doege-Potter syndrome
from 1979 to 2011 was obtained through Medline. This typical case, diagnosed and
confirmed by histopathologic results, was a 72-year-old Chinese woman who had a
complaint of night sweat for a month. A localized mass 12 cm * 11 cm * 8 cm in
size was found associated with pleural effusion in her left low chest cavity, and
blood tests showed severe hypoglycemia. Removal of the mass solved the
hypoglycemia. The case was repeatedly recurrent in April, 2010 and March, 2011
and had no signs of recurrence up to the end of 2011 after surgery. A review of
45 cases of solitary fibrous tumor of the pleura with Doege-Potter syndrome
compared and summarized clinical characteristics, treatments, and outcomes by
benign and malignant tumor nature. CONCLUSIONS: Incidence of solitary fibrous
tumor of the pleura with Doege-Potter syndrome is similar between genders. There
are no significant differences in clinical characteristics between benign and
malignant cases. Surgery is the first effective treatment for solitary fibrous
tumor of the pleura with Doege-Potter syndrome and the completeness of the
initial resection is the key to preventing recurrence. Routine follow-up
examinations are recommended for early detection of recurrence.
PMID- 25113506
TI - Urokinase-type plasminogen activator receptor regulates apoptotic sensitivity of
colon cancer HCT116 cell line to TRAIL via JNK-p53 pathway.
AB - The urokinase-type plasminogen activator receptor (uPAR) serves not only as an
anchor for urokinase-type plasminogen activator but also participates in
intracellular signal transduction events. In this study, we investigated whether
uPAR could modulate TRAIL-induced apoptosis in human colon cancer cells HCT116.
Using an antisense strategy, we established a stable HCT116 cell line with down
regulated uPAR. The sensitivity to TRAIL-induced apoptosis was evaluated by FACS
analysis. Our results show that the inhibition of uPAR could sensitize HCT116 to
TRAIL-induced apoptosis. uPAR inhibition changed the expression of mitochondrial
apoptotic pathway proteins, including Bcl-2, Bax, Bid and p53, in a pro-apoptotic
manner. We also found that the inhibition of uPAR down-regulated the
phosphorylation of FAK, ERK and JNK. The inhibition of p53 by RNA interference
rescued cells from enhanced apoptosis, thus indicating that p53 is critical for
enhancing TRAIL-induced apoptosis. Furthermore, JNK, but not ERK, inhibition
involved in the up-regulation of p53. JNK negatively regulated p53 protein level.
Overall, our results show that uPAR inhibition can sensitize colon cancer cells
HCT116 to TRAIL-induced apoptosis via active p53 and mitochondrial apoptotic
pathways that JNK inhibition is involved.
PMID- 25113507
TI - XI-011 enhances cisplatin-induced apoptosis by functional restoration of p53 in
head and neck cancer.
AB - Head and neck cancer (HNC), one of the most common cancers worldwide, frequently
involves mutation of the TP53 gene and dysregulation of the p53 pathway.
Overexpression of MDM2 or MDM4 inactivates the tumor-suppressive function of p53.
Restoration of p53 function that counteracts these p53 repressors can lead to in
vivo tumor regression. Therefore, the present study assessed the ability of the
small molecule p53 activator XI-011 (NSC146109) to induce apoptosis in HNC by
restoring p53 function. We tested the effects of XI-011 treatment in HNC cell
lines, either individually or in combination with cisplatin and assessed growth
suppression, cell cycle arrest, and apoptosis. The drug effects on in vivo growth
of HNC cells were examined in mice xenograft model. XI-011 exerted the highest
growth suppression in tumor cells that overexpress MDM4, in which p53 is
degraded. XI-011 treatment downregulated MDM4 mRNA and protein levels, and
upregulated expression of proapoptotic genes and promoted apoptosis, in a dose
dependent manner. The apoptotic response was blocked by inhibition of p53 or
expression of MDM4, demonstrating that the effects of XI-011 depend on p53 and
MDM4. In combination treatments, XI-011 acted synergistically with cisplatin to
inhibit growth of HNC cells in vitro and in vivo. MDM4 inhibition and functional
restoration of p53 by XI-011 effectively enhanced cisplatin-induced cytotoxicity
in HNC cells, an activity that suggests a promising strategy for treating HNC.
PMID- 25113508
TI - Dexamethasone's effect in the retrocochlear auditory centers of a noise-induced
hearing loss mouse model.
AB - OBJECTIVE: Examine prophylactic effects of dexamethasone (Dex) in retrocochlear
auditory centers in a noise-induced hearing loss (NIHL) mouse model. STUDY
DESIGN: Prospective animal study. SETTING: Academic research center. SUBJECTS AND
METHODS: Thirty-two mice were divided into control, untreated, saline (2 and 10
uL), and Dex (2 and 10 uL) groups. Dex was applied intratympanically (IT) prior
to 110 to 120 dB noise over 6 hours. Auditory brainstem response (ABR) and
distortion product otoacoustic emission (DPOAE) were performed at 1 day, 1 week,
1 month, and 2 months. Retrocochlear neuronal cells were labeled with FluoroGold
and counted. Hair cells of the organ of Corti were labeled with fluorescein
isothiocyanate-conjugated phalloidin and counted. RESULTS: Auditory brainstem
response thresholds of untreated NIHL, 2 and 10 uL IT saline, and 2 and 10 uL IT
Dex were 21.7 +/- 2.9 dB, 20 +/- 0 dB, 20 +/- 5 dB, 18.3 +/- 2.9 dB, and 18.3 +/-
2.9 dB, respectively. At 1-day post NIHL, all groups demonstrated profound
hearing loss. At 2 weeks, 2 and 10 uL Dex thresholds improved to 47.5 +/- 3.5 dB
and 48.8 +/- 18.9 dB, respectively, whereas the untreated and saline groups
remained unchanged. Mean cell counts in the cochlear nucleus (CN), superior
olivary complex (SOC), and lateral lemniscus (LL) of control mice were 1483 +/-
190, 2807 +/- 67, and 112 +/- 20, respectively. After acoustic trauma, the
untreated, saline, and 2 uL Dex groups yielded decreased neuronal counts in the
SOC. In contrast, the 10 uL Dex group had 1883 +/- 186 (CN), 2774 +/- 182 (SOC),
and 166 +/- 18 (LL). There was sporadic hair cell loss for all traumatized
groups. CONCLUSION: Our NIHL mouse model demonstrated dose-dependent Dex
pretreatment otoprotection against NIHL with preservation of retrocochlear
auditory neurons.
PMID- 25113509
TI - Preemptive submucosal infiltration with ropivacaine for
uvulopalatopharyngoplasty.
AB - OBJECTIVE: To evaluate the preemptive analgesic effect of submucosal infiltration
of ropivacaine for uvulopalatopharyngoplasty. STUDY DESIGN: Randomized controlled
trial. SETTING: Comprehensive clinical center and academic hospital. SUBJECTS AND
METHODS: Fifty consecutive male patients scheduled for uvulopalatopharyngoplasty
were divided randomly into group A and group B. In group A, 4 mL of 0.33%
ropivacaine and normal saline with epinephrine was preincisionally injected under
the mucosa on both sides of the tonsillar fossa, soft palate, and the lower part
of palatoglossal arch, whereas the upper and middle parts of the palatoglossal
arch and the upper part of the palatopharyngeal arch were infiltrated with 2 mL
of the same mixture. In group B, an identical volume of normal saline with
epinephrine was administered. In both groups, postoperative pain was initially
controlled by intravenous morphine titration until patient-controlled analgesia
with morphine could be used. Cumulative patient-controlled analgesic morphine
consumption; visual analog scale scores at 4, 8, 12, 24, and 48 hours
postoperatively at rest and during swallowing; and opioid-related adverse effects
were recorded. RESULTS: The visual analog score was lower at rest during the 48
hour postoperative period and during swallowing within the first 12 hours for
group A versus group B (P < .05). Patients in group A required 44.1%, 38.2%, and
41.1% less morphine during the first 24 hours, 24 hours to 48 hours, and 48 hours
postoperatively, respectively, and fewer patients experienced nausea, vomiting,
and pruritus (P < .05). CONCLUSION: Preemptive submucosal infiltration with 0.33%
ropivacaine effectively controlled pain after uvulopalato-pharyngoplasty.
PMID- 25113510
TI - Improving atrial fibrillation detection in patients with implantable cardiac
devices by means of a remote monitoring and management application.
AB - BACKGROUND: Atrial fibrillation (AF) is common in patients with cardiac
implantable electronic devices (CIED) and has been associated with an increased
stroke risk. The aim of our project was to assess the clinical value of a web
based application, Discovery Link AFinder, in improving AF detection in CIED
patients. METHODS AND RESULTS: Seven Italian hospitals performed an observational
study consisting of four phases. During phase 1, expert nurses and cardiologists
prospectively followed-up CIED patients via in-hospital examinations and remote
monitoring, and classified clinically relevant events, particularly AF
occurrence. During phase 2, Discovery Link AFinder was exploited to identify
patients who had suffered AF in the previous 12 months through the systematic
scanning of device data remote transmissions. Phases 3 and 4 were repetitions of
phases 1 and 2, respectively, and were implemented 6 months after the previous
phases. A total of 472 consecutive patients were included in phase 1; AF occurred
in 170 patients, 61 of whom were identified as new AF patients. Evidence of AF
during this phase prompted prescription of oral anticoagulation (OAC) therapy in
30 patients. In phase 2, AFinder uncovered new AF, unidentified in phase 1, in 54
patients and prompted implementation of OAC therapy in 11 patients. During phase
3, 30 new AF patients were identified by means of remote monitoring, while during
phase 4, a further three AF patients were identified by AFinder only.
CONCLUSIONS: The AFinder web-based software, applied on top of standard in
hospital and remote monitoring, improved AF detection and enabled OAC treatment
to be undertaken.
PMID- 25113511
TI - Distribution of tension wood like gelatinous fibres in the roots of Acacia
nilotica (Lam.) Willd.
AB - KEY MESSAGE: The present study unravels the anatomical characteristics and
distribution patterns of cell wall polymers in the G-fibres found in the roots of
A. nilotica using different microscopy techniques (light, electron and
immunofluorescence microscopy). The present study was aimed to investigate the
anatomy of reaction xylem in the positively gravitropic roots of Acacia nilotica
growing in compact and waterlogged soils. The roots collected from the two
different sites showed occurrence of gelatinous fibres throughout xylem radii
from a distance of 4 cm from the soil surface. The thickness of gelatinous layer
(G-layer) increased in the root collected from the deeper soil. Further, the
ultrastructural studies revealed a complete replacement of S2 and S3 layers in G
fibres nearer to root tip region as compared to the root portion close to upper
part of the soil surface. In addition, these fibres demonstrated intense
lignification in compound middle lamellae region of G-fibre walls. Moreover, the
vessel density and their width increased considerably near the root tip region.
The immunofluorescence analysis suggested that the beta-1,4-galactans were
prevalent in G-layer, whereas the xylan was restricted to only regions of
lignified secondary wall. The similarities in distribution pattern and anatomical
features of G-fibres in waterlogged and non-waterlogged roots suggest the
occurrence of G-fibres as inherent characteristics in the roots of Acacia
nilotica.
PMID- 25113512
TI - Connection between expression of inducible nitric oxide synthase (iNOS) in skull
base chordoma and lower urinary tract symptoms.
AB - OBJECTIVE: To provide first insights into the potential role of iNOS expressed by
skull base chordoma, which causes brainstem compression in and around
Barrington's nucleus, and its effect on the micturition center. METHODS:
Urodynamic testing of 22 symptomatic patients was performed. All women and men
with skull base chordoma treated in two hospitals in Germany between 1986 and
2007 were studied. Lower urinary tract symptoms (LUTS) were documented in
patients with acute brainstem compression due to local chordoma growth positive
for iNOS expression. Brain magnetic resonance (MRI) images of the lesions of the
symptomatic patients were performed. RESULTS: Of 74 treated patients, 22 (7
women, 15 men) with a median age of 37 years were evaluated with voiding diaries
and computer urodynamic investigation. Urodynamic testing of 22 symptomatic
patients with positive iNOS expression of skull base chordoma revealed detrusor
overactivity in 55 %, low-compliance bladder in 14 %, detrusor sphincter
dyssynergia in 45 % and uninhibited sphincter relaxation in 27 %. There was a
significant correlation between strong iNOS expression (score 3-6) in skull base
chordoma and severe urinary symptoms (p = 0.003, Spearman rho = 0.526).
CONCLUSIONS: The expression of iNOS in skull base chordoma compressing the
dorsolateral pons, in and around Barrington's nucleus, may influence the pontine
micturition center (PMC) and be responsible for lower urinary tract symptoms.
Nitric oxide may possibly act as a neurotransmitter. We assume that the high
infiltration of chordoma with monocyte/macrophages enhances the release of nitric
oxide, as monocyte/macrophages are the main source of iNOS.
PMID- 25113513
TI - Incidence of pineal tumours. A review of the literature.
AB - The knowledge of the incidence of pineal tumours is important not only for
diagnostic care but also for its therapeutic programme. We reviewed the incidence
of pineal tumours reported in literature in an attempt to establish if a
difference existed between pineal gland tumours and the pineal region tumours as
different authors use both expressions to indicate the same thing. The rate of
frequency of these tumours is useful to guide the therapeutic choice for patients
as the decisional tree is completely different for either germ cell tumours,
pineal gland tumours or pineal gliomas and eventually papillary tumours of the
pineal region. According to the French Register of pineal tumours, true pineal
tumours represent: 27% pineal parenchymal tumours (PPT), 27% germ cell tumours,
17% gliomas, 8% papillary tumours. True pineal gland tumours are represented by:
pineocytomas - (13%), pineal parenchymal tumours with intermediary
differentiation PTT-ID - (66%) and pinealoblastomas - (21%). There was no
statistical difference found between the French register and the Lyon series
concerning histological diagnosis. It seemed to us important to discover its true
incidence by comparing the data published in the literature and to stress the
utility of the French Register for these uncommon tumours not only for recording
new histological cases but also to document clinical symptomatology, therapeutic
programmes, length of follow-up and clinical results for each patient treated. A
better understanding of their natural history and improved evaluation of
different treatments and their complications should contribute to improve
clinical results.
PMID- 25113514
TI - Review of environmental exposure concentrations of chemical warfare agent
residues and associated the fish community risk following the construction and
completion of the Nord Stream gas pipeline between Russia and Germany.
AB - This paper compiles all the measured chemical warfare agent (CWA) concentrations
found in relation to the Nord Stream pipeline work in Danish waters for the past
5 years. Sediment and biota sampling were performed along the pipeline route in
four campaigns, prior to (in 2008 and 2010), during (in 2011) and after (in 2012)
the construction work. No parent CWAs were detected in the sediments. Patchy
residues of CWA degradation products of Adamsite, Clark I, phenyldichloroarsine,
trichloroarsine and Lewisite II, were detected in a total of 29 of the 391
sediment samples collected and analyzed the past 5 years. The cumulative fish
community risk quotient for the different locations, calculated as a sum of
background and added risk, ranged between 0 and 0.017 suggesting a negligible
acute CWA risk toward the fish community. The added risk from sediment
disturbance in relation to construction of the pipelines represents less than 2%
of the total risk in the areas with the highest calculated risk. The analyses of
benthic infauna corroborate the finding of CWA related low risk across the years.
There was no significant difference in CWA risk before (2008) and after the
pipeline construction (2012).
PMID- 25113515
TI - K4Nb6O17.4.5H2O: a novel dual functional material with quick photoreduction of
Cr(VI) and high adsorptive capacity of Cr(III).
AB - A series of orthorhombic phase K4Nb6O17.4.5H2O was synthesized via a hydrothermal
approach. When presented in an acidic pH range, K4Nb6O17.4.5H2O showed a strong
ability in quick reduction from Cr(VI) to Cr(III). The resulted Cr(III) ions were
removed by an effective adsorption through simply adjusting the solution pH from
strong acidity to near neutrality, owing to the sample's unique nano-sheet
structure with a wide layer spacing. The Cr(III) ions adsorbed onto samples were
released again for reusing by eluting with 1molL(-1) HCl solution, and
K4Nb6O17.4.5H2O regenerated by immersing in a KOH solution. The reduction
efficiency of Cr(VI) was still up to 98% after irradiation for 60min, and the
removal efficiency of Cr(III) ions was as high as 83% even after five cycles.
Therefore, K4Nb6O17.4.5H2O is clearly demonstrated to be an excellent dual
functional material with quick photoreduction of Cr(VI) and high adsorptive
capacity of Cr(III). The relevant materials reported herein might be found
various environment-related applications.
PMID- 25113516
TI - Iron amendments to reduce bioaccessible arsenic.
AB - Former sugarcane lands on the Island of Hawaii have elevated levels of soil
arsenic (As) from historical use of arsenical pesticides. The bioaccessible
fraction of total As (AsTOT), a measure of the potential for human As uptake by
incidental ingestion of soil, is used in the assessment of human health risk and
the determination of the need for remedial action. Ferric chloride plus lime and
ferrous sulfate plus lime were applied to As-contaminated soils in a field plot
setting to determine the potential for reducing in vitro bioaccessible As
(AsIVBA) by increasing As sequestration by the formation of additional iron (Fe)
oxyhydroxides. The two Fe sources performed similarly in reducing AsIVBA over a 2
year observation period, with 30-41% reduction in AsIVBA for 0.25wt% Fe dosing
(dry soil basis) and 59-63% reduction for 0.5wt% Fe dosing. Addition of phosphate
(PO4) to treated and untreated soils caused a significant increase in AsIVBA.
Iron-treated and control soils showed more than twice the AsIVBA after the
addition of 1500mgPkg(-1). The cost of in situ treatment of As-contaminated soil
with ferrous sulfate plus lime to lower AsIVBA was estimated to be an order of
magnitude less than excavation and landfill disposal on the Island of Hawaii,
making the technology a viable alternative when remedial action objectives were
based on AsIVBA levels.
PMID- 25113518
TI - The efficiency of quartz addition on electric arc furnace (EAF) carbon steel slag
stability.
AB - Electric arc furnace slag (EAF) has the potential to be re-utilized as an
alternative to stone material, however, only if it remains chemically stable on
contact with water. The presence of hydraulic phases such as larnite (2CaO SiO2)
could cause dangerous elements to be released into the environment, i.e. Ba, V,
Cr. Chemical treatment appears to be the only way to guarantee a completely
stable structure, especially for long-term applications. This study presents the
efficiency of silica addition during the deslagging period. Microstructural
characterization of modified slag was performed by SEM and XRD analysis. Elution
tests were performed according to the EN 12457-2 standard, with the addition of
silica and without, and the obtained results were compared. These results
demonstrate the efficiency of the inertization process: the added silica induces
the formation of gehlenite, which, even in caustic environments, does not exhibit
hydraulic behaviour.
PMID- 25113517
TI - The critical role of the operating conditions on the Fenton oxidation of 2
chlorophenol: assessment of PCDD/Fs formation.
AB - This work assesses the influence of the operating conditions H2O2 dose (20 or
100% of the stoichiometric amount), temperature (20 or 70 degrees C), and the
presence of chloride in the oxidation medium in the formation of polychlorinated
dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) during Fenton treatment of aqueous
samples of 2-chlorophenol, 2-CP, one of the strongest precursor of PCDD/Fs. After
4h of oxidation in the experiments carried out with 20% H2O2 chlorinated
phenoxyphenols and biphenyls, which are intermediates in PCDD/Fs formation, as
well as PCDD/Fs were observed, resulting in concentrations 11 times higher than
in the untreated sample. Additionally, when NaCl was also present in the reaction
medium, PCDD/Fs were formed at higher extent, with a total concentration 74.4
times higher than in the untreated 2-CP solution. Results depicted a preferential
formation of PCDFs over PCDDs, with dominance of lower chlorinated PCDD/Fs (tetra
and penta-PCDD/Fs). Besides, the formation of the most toxic PCDD/Fs congeners
(2,3,7,8-PCDD/Fs) was not favored under the operating conditions used in this
work.
PMID- 25113519
TI - The effects of dexmedetomidine administration on the pulmonary artery pressure
and the transpulmonary pressure gradient after the bidirectional superior
cavopulmonary shunt.
AB - The hemodynamic effects of dexmedetomidine (DEX) on pulmonary artery pressure
(PAP) are not fully understood in patients with a single-ventricle physiology.
The objective of this retrospective study was to characterize the effect of
perioperative DEX infusion on PAP and the transpulmonary pressure gradient after
a bidirectional superior cavopulmonary shunt (BCPS) operation. We retrieved
physiologic data including the heart rate, incidence of cardiac pacing, systolic
and diastolic arterial blood pressure (ABP), and superior vena cava (SVC) and
inferior vena cava (IVC) pressures from the medical records of all patients <12
months of age who underwent a BCPS operation. Patients with an additional Norwood
or Damus-Kaye-Stansel procedure, those with additional pulmonary blood flow, and
those without both a SVC and an IVC catheter were excluded from the present
study. Following the BCPS operation, the SVC pressure is equivalent to the PAP.
Similarly, the IVC pressure is equivalent to the common atrial pressure (CAP).
Accordingly, we can directly assess the transpulmonary pressure gradient, defined
as the difference between the PAP and the CAP, using simultaneous SVC and IVC
pressure measurements. Twenty-nine patients were included in the present study.
We did not find any increase in the PAP, CAP, PAP/systolic ABP ratio, or the
transpulmonary pressure gradient as of 6 h after admission to the intensive care
unit when the patients were treated with DEX infusion at a median (interquartile
ranges) dose of 0.6 mcg/kg/h (0.4, 0.64 mcg/kg/h). We concluded that the
administration of DEX to children with a single-ventricle physiology is
acceptable.
PMID- 25113520
TI - Development of a charge adjustment model for cardiac catheterization.
AB - A methodology that would allow for comparison of charges across institutions has
not been developed for catheterization in congenital heart disease. A single
institution catheterization database with prospectively collected case
characteristics was linked to hospital charges related and limited to an episode
of care in the catheterization laboratory for fiscal years 2008-2010.
Catheterization charge categories (CCC) were developed to group types of
catheterization procedures using a combination of empiric data and expert
consensus. A multivariable model with outcome charges was created using CCC and
additional patient and procedural characteristics. In 3 fiscal years, 3,839 cases
were available for analysis. Forty catheterization procedure types were
categorized into 7 CCC yielding a grouper variable with an R (2) explanatory
value of 72.6%. In the final CCC, the largest proportion of cases was in CCC 2
(34%), which included diagnostic cases without intervention. Biopsy cases were
isolated in CCC 1 (12%), and percutaneous pulmonary valve placement alone made up
CCC 7 (2%). The final model included CCC, number of interventions, and cardiac
diagnosis (R (2) = 74.2%). Additionally, current financial metrics such as APR
DRG severity of illness and case mix index demonstrated a lack of correlation
with CCC. We have developed a catheterization procedure type financial grouper
that accounts for the diverse case population encountered in catheterization for
congenital heart disease. CCC and our multivariable model could be used to
understand financial characteristics of a population at a single point in time,
longitudinally, and to compare populations.
PMID- 25113521
TI - Effect of hypercrosslinking conditions on pore size distribution and efficiency
of monolithic stationary phases.
AB - Three dihalogenic solvents differing in the length of alkyl chain (1,2
dichloroethane, 1,4-dichlorobutane, and 1,6-dichlorohexane) with three Friedel
Crafts alkylation catalysts varying in reactivity (AlCl3 , FeCl3 , and SnCl4 )
have been used to prepare hypercrosslinked poly(styrene-co-vinylbenzyl chloride
co-divinylbenzene) columns. Hydrodynamic characteristics as well as column
efficiency and mass transfer resistance were tuned by the combination of swelling
solvent and alkylation reaction catalyst in the modification mixture. The column
swelled in 1,6-dichlorohexane and hypercrosslinked in the presence of AlCl3
provided the highest column efficiency and enabled fast isocratic separations of
small molecules in a RP mode. To uncover factors controlling the efficiency of
hypercrosslinked monolithic columns, we have studied pore volume distribution of
prepared columns. We found that column efficiency increases with the higher pore
volume of pores smaller than 2 nm.
PMID- 25113522
TI - A combined high CYP2D6-CYP2C19 metabolic capacity is associated with the severity
of suicide attempt as measured by objective circumstances.
AB - This study examined, for the first time, whether a high CYP2D6-CYP2C19 metabolic
capacity combination increases the likelihood of suicidal intent severity in a
large study cohort. Survivors of a suicide attempt (n=587; 86.8% women) were
genotyped for CYP2C19 (*2, *17) and CYP2D6 (*3, *4, *4xN, *5, *6, *10, wtxN)
genetic variation and evaluated with the Beck Suicide Intent Scale (SIS).
Patients with a high CYP2D6-CYP2C19 metabolic capacity showed an increased risk
for a severe suicide attempt (P<0.01) as measured by the SIS-objective
circumstance subscale (odds ratio (OR)=1.37; 95% confidence interval (CI)=1.05
1.78; P=0.02) after adjusting for confounders (gender, age, level of studies,
marital status, mental disorders, tobacco use, family history of suicide,
personal history of attempts and violence of the attempt). Importantly, the risk
was greater in those without a family history of suicide (OR=1.82; CI=1.19-2.77;
P=0.002). Further research is warranted to evaluate whether the observed
relationship is mediated by the role of CYP2D6 and CYP2C19 involvement in the
endogenous physiology or drug metabolism or both.
PMID- 25113523
TI - Societal cost-of-illness in patients with borderline personality disorder one
year before, during and after dialectical behavior therapy in routine outpatient
care.
AB - Societal cost-of-illness in a German sample of patients with borderline
personality disorder (BPD) was calculated for 12 months prior to an outpatient
Dialectical Behavior Therapy (DBT) program, during a year of DBT in routine
outpatient care and during a follow-up year. We retrospectively assessed resource
consumption and productivity loss by means of a structured interview. Direct
costs were calculated as opportunity costs and indirect costs were calculated
according to the Human Capital Approach. All costs were expressed in Euros for
the year 2010. Total mean annual BPD-related societal cost-of-illness was ?28026
(SD = ?33081) during pre-treatment, ?18758 (SD = ?19450) during the DBT treatment
year for the 47 DBT treatment completers, and ?14750 (SD = ?18592) during the
follow-up year for the 33 patients who participated in the final assessment. Cost
savings were mainly due to marked reductions in inpatient treatment costs, while
indirect costs barely decreased. In conclusion, our findings provide evidence
that the treatment of BPD patients with an outpatient DBT program is associated
with substantial overall cost savings. Already during the DBT treatment year,
these savings clearly exceed the additional treatment costs of DBT and are
further extended during the follow-up year. Correspondingly, outpatient DBT has
the potential to be a cost-effective treatment for BPD patients. Efforts
promoting its implementation in routine care should be undertaken.
PMID- 25113525
TI - Prevalence, correlates, and comorbidities of DSM-IV psychiatric disorders in
children in Seoul, Korea.
AB - The present study reports past-year prevalence of and comorbidities associated
with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
(DSM-IV) disorders in 1645 children aged 6 to 12 years in Seoul, Korea. The
diagnosis was based on the parental version of the Diagnostic Interview Schedule
for Children (DISC-IV). Our participants completed the Children's Depression
Inventory (CDI). The estimated prevalence of any full-syndrome and subthreshold
DSM-IV disorders were 16.2% and 28.1%, respectively. The most prevalent disorders
were specific phobia (9.6%), attention-deficit hyperactivity disorder (ADHD;
5.9%), and oppositional defiant disorder (ODD; 4.9%). The estimated prevalence of
depressive disorder was 0.1% according to the DISC-IV and1.9% according to the
CDI. ADHD, ODD, and anxiety disorders were highly comorbid. Our study highlights
the importance of obtaining children's self-report data in addition to the
parents' interview, particularly for depression, and the importance of early
detection of subthreshold conditions and considering comorbid diagnoses.
PMID- 25113526
TI - The impact of the environment on health in Mongolia: a systematic review.
AB - Mongolia has significant exposure to environmental risk factors because of poor
environmental management and behaviors, and children are increasingly vulnerable
to these threats. This study aimed to assess levels of exposure and summarize the
evidence for associations between exposures to environmental risk factors and
adverse health outcomes in Mongolia, with a particular focus on children. A
systematic review was conducted using the PubMed, EMBASE, Web of Science, Global
Health Library, CINAHL, CABI, Scopus, and mongolmed.mn electronic databases up to
April 2014 . A total of 59 studies meeting the predetermined criteria were
included. Results indicate that the Mongolian population has significant exposure
to outdoor and indoor air pollution, metals, environmental tobacco smoke, and
other chemical toxins, and these risk factors have been linked to respiratory and
cardiovascular diseases among adults and respiratory diseases and
neurodevelopmental disorders among children. Well-designed epidemiological
investigations in vulnerable populations especially in pregnant women and
children are recommended.
PMID- 25113524
TI - A randomized controlled trial of an internet-based therapist-assisted indicated
preventive intervention for prolonged grief disorder.
AB - This trial assessed the feasibility, acceptability, tolerability, and efficacy of
an Internet-based therapist-assisted cognitive-behavioral indicated prevention
intervention for prolonged grief disorder (PGD) called Healthy Experiences After
Loss (HEAL). Eighty-four bereaved individuals at risk for PGD were randomized to
either an immediate treatment group (n = 41) or a waitlist control group (n =
43). Assessments were conducted at four time-points: prior to the wait-interval
(for the waitlist group), pre-intervention, post-intervention, 6 weeks later, and
3 months later (for the immediate group only). Intent-to-treat analyses indicated
that HEAL was associated with large reductions in prolonged grief (d = 1.10),
depression (d = .71), anxiety (d = .51), and posttraumatic stress (d = .91).
Also, significantly fewer participants in the immediate group met PGD criteria
post-intervention than in the waitlist group. Pooled data from both groups also
yielded significant reductions and large effect sizes in PGD symptom severity at
each follow-up assessment. The intervention required minimal professional
oversight and ratings of satisfaction with treatment and usability of the
Internet interface were high. HEAL has the potential to be an effective, well
tolerated tool to reduce the burden of significant pre-clinical PGD. Further
research is needed to refine HEAL and to assess its efficacy and mechanisms of
action in a large-scale trial.
PMID- 25113527
TI - Efavirenz modulation of sleep spindles and sleep spectral profile.
AB - Non-nucleoside reverse transcriptase inhibitors are important antiretroviral
agents for the treatment of human immunodeficiency virus. Some non-nucleoside
reverse transcriptase inhibitors, in particular efavirenz, have prominent effects
on sleep, cognition and psychiatric variables that limit their tolerability. To
avoid confounds due to drug-drug and drug-disease interactions, we assessed the
effects of efavirenz in healthy volunteers on sleep, cognition and psychological
endpoints during the first week of treatment. Forty healthy male subjects were
randomized to receive placebo or efavirenz 600 mg nightly for 7 days after
completion of a 3-day placebo run-in period. Treatment with efavirenz was
associated with reduced time to sleep onset in the Maintenance of Wakefulness
Test, an increase in non-rapid eye movement sleep, a large exposure-related
decrease in sigma band spectral density and sleep spindle density during non
rapid eye movement sleep, and reduced performance on an attention switching task.
Because efavirenz has been shown to have serotonin 2A receptor partial-agonist
properties, we reasoned that antagonism of serotonin 2A receptor signalling in
the thalamic reticular nucleus, which generates sleep spindles and promotes
attention, may be responsible. Consistent with predictions, treatment of healthy
volunteers with a single dose of a serotonin 2A receptor antagonist was found to
significantly suppress sigma band spectral density in an exposure-related manner
and modulated the overall spectral profile in a manner highly similar to that
observed with efavirenz, consistent with the notion that efavirenz exhibits
serotonin 2A receptor partial-agonist pharmacology in humans.
PMID- 25113531
TI - Rapid progression of perianal abscess into Fournier's gangrene.
PMID- 25113528
TI - Quality of life among people living with hypertension in a rural Vietnam
community.
AB - BACKGROUND: To respond to growing prevalence of hypertension in Vietnam, it is
critical to have an in-depth understanding about quality of life (QOL) among
people living with hypertension and related factors. This study aimed to measure
QOL among hypertensive people in a rural community in Vietnam, and its
association with socio-demographic characteristics and factors related to
treatment. METHODS: This study was conducted in a rural community located 60 km
from Ho Chi Minh City. Face-to-face interviews were conducted among 275
hypertensive people aged 50 years and above using WHOQOL-BREF questionnaire.
Descriptive statistics were used to examine mean scores of quality of life.
Cronbach's alpha coefficient and Pearson's correlation coefficient were applied
to estimate the internal consistency, and the level of agreement between
different domains of WHOQOL-BREF, respectively. Independent T-test and ANOVA test
followed by multiple linear regression analyses were used to measure the
association between QOL domains and independent variables. RESULTS: Both overall
WHOQOL-BREF and each domain had a good internal consistency, ranging from 0.65 to
0.88. The QOL among hypertensive patients was found moderate in all domains,
except for psychological domain that was fairly low (mean = 49.4). Backward
multiple linear regressions revealed that being men, married, attainment of
higher education, having physical activities at moderate level, and adherence to
treatment were positively associated with QOL. However, older age and presence of
co-morbidity were negatively associated with QOL. CONCLUSION: WHOQOL-BREF is a
reliable instrument to measure QOL among hypertensive patients. The results
revealed low QOL in psychological domain and inequality in QOL across socio
demographic characteristics. Given the results, encouraging physical activities
and strengthening treatment adherence should be considered to improve QOL of
hypertensive people, especially for psychological aspect. Actions to improve QOL
among hypertensive patients targeted towards women, lower educated and unmarried
patients are needed in the setting.
PMID- 25113533
TI - Special issue on "Oxidative stress and mitochondrial alterations in aging and
disease".
PMID- 25113532
TI - Infection with human rhinovirus 16 promotes enhanced IgE responsiveness in
basophils of atopic asthmatics.
AB - BACKGROUND: Rhinovirus and IgE act in concert to promote asthma exacerbations.
While basophils are the principal cell type in the blood that is activated by
IgE, their role in virus-induced asthma episodes remains elusive. OBJECTIVE: To
monitor IgE responsiveness in circulating basophils of rhinovirus-infected atopic
asthmatics during acute infection and convalescence. METHODS: The capacity for
basophils to respond to IgE was assessed by testing the effects of allergen, or
cross-linking anti-FcepsilonRI and anti-IgE antibodies, on surface TSLP receptor
in 24-hour PBMC cultures. Activation profiles of basophils from atopic asthmatics
challenged intranasally with human rhinovirus 16 were monitored directly ex vivo
or else in 24-hour cultures, at baseline (day 0), and then at days 4 and 21 post
challenge. RESULTS: Basophils in atopic asthmatics, but not in non-atopic
controls, upregulated TSLP receptor upon IgE receptor ligation. The magnitude of
this response was correlated with the proportion of serum total IgE that was
allergen-specific (r = 0.615, P < 0.05). Following rhinovirus infection, all
subjects developed nasal symptoms that peaked 3-5 days after viral challenge.
Basophils displayed maximal IgE responsiveness 3 weeks post-challenge as judged
by TSLP receptor levels in 24-hour cultures. No significant change in total IgE
or specific IgE antibodies was detected during rhinovirus infection. By contrast,
levels of IgE receptor-associated spleen tyrosine kinase, Syk, were increased on
day 4 (P < 0.05), and elevated levels were also detected three weeks post
challenge. CONCLUSIONS AND CLINICAL RELEVANCE: Circulating basophils display
increased IgE responsiveness 3 weeks after rhinovirus infection in atopic
asthmatics. This observation, coupled with increased expression of Syk,
implicates basophils in promoting, or else prolonging, rhinovirus-induced
inflammation in atopic asthmatics.
PMID- 25113535
TI - Improved synthesis of [(18)F]FLETT via a fully automated vacuum distillation
method for [(18)F]2-fluoroethyl azide purification.
AB - The synthesis of [(18)F]2-fluoroethyl azide and its subsequent click reaction
with 5-ethynyl-2'-deoxyuridine (EDU) to form [(18)F]FLETT was performed using an
iPhase FlexLab module. The implementation of a vacuum distillation method
afforded [(18)F]2-fluoroethyl azide in 87+/-5.3% radiochemical yield. The use of
Cu(CH3CN)4PF6 and TBTA as catalyst enabled us to fully automate the [(18)F]FLETT
synthesis without the need for the operator to enter the radiation field.
[(18)F]FLETT was produced in higher overall yield (41.3+/-6.5%) and shorter
synthesis time (67min) than with our previously reported manual method (32.5+/
2.5% in 130min).
PMID- 25113536
TI - Excel2Genie: A Microsoft Excel application to improve the flexibility of the
Genie-2000 Spectroscopic software.
AB - Excel2Genie, a simple and user-friendly Microsoft Excel interface, has been
developed to the Genie-2000 Spectroscopic Software of Canberra Industries. This
Excel application can directly control Canberra Multichannel Analyzer (MCA),
process the acquired data and visualize them. Combination of Genie-2000 with
Excel2Genie results in remarkably increased flexibility and a possibility to
carry out repetitive data acquisitions even with changing parameters and more
sophisticated analysis. The developed software package comprises three
worksheets: display parameters and results of data acquisition, data analysis and
mathematical operations carried out on the measured gamma spectra. At the same
time it also allows control of these processes. Excel2Genie is freely available
to assist gamma spectrum measurements and data evaluation by the interested
Canberra users. With access to the Visual Basic Application (VBA) source code of
this application users are enabled to modify the developed interface according to
their intentions.
PMID- 25113534
TI - Microscopy and genomic analysis of Mycoplasma parvum strain Indiana.
AB - Mycoplasma parvum [Eperythrozoon parvum] is the second hemotrophic mycoplasma
(hemoplasma) described in pigs. Unlike M. suis, its closest phylogenetic
relative, M. parvum, is considered a non-pathogenic bacterium in this host
species. Natural infection of a domestic, 6-month-old splenectomized pig with M.
parvum strain Indiana is described herein. Light and scanning electron microscopy
of the bacteria were performed in addition to whole genome sequencing, analysis,
and comparison to the genome of M. suis strain Illinois. Neither clinical signs
nor anemia were observed during the infection. Microscopy analyses revealed
coccoid to rod- shaped organisms varying from 0.2 to 0.5 MUm; they were observed
individually or in short chains by both light and electron microscopy, however
less than 30% of the red blood cells were infected at peak bacteremia. The single
circular chromosome of M. parvum was only 564 395 bp, smaller than M. genitalium,
previously considered the tiniest member of the Mollicutes. Its general genomic
features were similar to others in this class and species circumscription was
verified by phylogenomic analysis. A gene-by-gene comparison between M. suis and
M. parvum revealed all protein coding sequences (CDS) with assigned functions
were shared, including metabolic functions, transporters and putative virulence
factors. However, the number of CDS in paralogous gene families was remarkably
different with about half as many paralogs in M. parvum. The differences in
paralogous genes may be implicated in the different pathogenic potential of these
two species, however variable gene expression may also play a role. Both are
areas of ongoing investigation.
PMID- 25113537
TI - A semi-empirical approach to analyze the activities of cylindrical radioactive
samples using gamma energies from 185 to 1764 keV.
AB - This work suggests a method for determining the activities of cylindrical
radioactive samples. The self-attenuation factor was applied for providing the
self-absorption correction of gamma rays in the sample material. The experimental
measurement of a (238)U reference sample and the calculation using the MCNP5 code
allow obtaining the semi-empirical formulae of detecting efficiencies for the
gamma energies ranged from 185 to 1764keV. These formulae were used to determine
the activities of the (238)U, (226)Ra, (232)Th, (137)Cs and (40)K nuclides in the
IAEA RGU-1, IAEA-434, IAEA RGTh-1, IAEA-152 and IAEA RGK-1 radioactive standards.
The coincidence summing corrections for gamma rays in the (238)U and (232)Th
series were applied. The activities obtained in this work were in good agreement
with the reference values.
PMID- 25113538
TI - [Tuberculosis, "a sustainable challenge"].
PMID- 25113540
TI - Species identification of strains belonging to genus Citrobacter using the
biochemical method and MALDI-TOF mass spectrometry.
AB - Strains of genus Citrobacter (152 isolates from 1950 to 1988 deposited in the
Czech National Collection of Type Cultures, Prague) were re-classified using
biological and matrix-assisted laser desorption/ionization time-of-flight mass
spectrometry (MALDI-TOF MS) methods. One-hundred thirty-six strains (ca. 90 %)
were identified to the species level using the biological method with evaluation
by Farmer matrix. MALDI-TOF MS exhibited better identification capability, the
data being more compact; the method was unambiguously successful in typing 145
(95 %) strains. Comparison of the results of identification by the two methods
revealed differences (for 12 samples) in identified species which, considering
all biochemical and/or MS characteristics, could be attributed to the natural
variability of strains and close relation of the misidentified species (all of
them belonged to the Citrobacter freundii complex). Taking into account all the
above data, both methods can be considered reliable; however, the MALDI-TOF MS
exhibits higher accuracy, efficiency, and rapidity.
PMID- 25113541
TI - Variation in riparian consumer diet composition and differential bioaccumulation
by prey influence the risk of exposure to elements from a recently remediated fly
ash spill.
AB - Emerging aquatic insects play a key role in transporting aquatic nutrients and
contaminants to riparian consumers. However, little is known about how within-
and between-year variation in the diet or patterns of element bioaccumulation in
emerging insect taxa may influence the risk of exposure to wildlife. During 2
breeding seasons, the composition of the diet of tree swallows (Tachycineta
bicolor) was examined at several colonies that were exposed to element
contamination from a remediated coal fly ash spill to determine how variation in
the diet influenced the risk of exposure to elements. The proportion of the diet
that consisted of insects with an aquatic larval stage was positively related to
concentrations of As, Fe, Se, and Tl in the samples. The proportion of the diet
that consisted of Chironomidae (midges) was positively related to exposure to
these elements at most colonies within and between years. Ephemeroptera
(mayflies) contained higher concentrations of Se than midges, including 17
samples with concentrations of Se above 5 ug/g dry mass, the threshold of
toxicological concern for birds. This was even the case at colonies several
kilometers downstream from the spill. The results indicate that greater
consideration should be given to the pattern of element bioaccumulation among
different prey taxa and their relative importance in the diet to better assess
the risk of contaminant exposure.
PMID- 25113539
TI - Genetics of Alzheimer's disease.
AB - The analyses of genetic factors contributing to Alzheimer's disease (AD) and
other dementias have evolved at the same pace as genetic and genomic technologies
are developed and improved. The identification of the first genes involved in AD
arose from family-based studies, but risk factors have mainly been identified by
studies comparing groups of patients with groups of controls. The best outcomes
have been heavily associated with the capacity of interrogating genetic
variability at the genome level without any particular a priori hypothesis. In
this review we assess the role of genetic family studies in Alzheimer's disease
and other dementias within the current status of dementias' and, particularly,
AD's genetic architecture.
PMID- 25113542
TI - Mechanical bowel obstruction due to occlusion with a biliary calculus: a case of
a 91-year-old woman with nausea and vomiting.
PMID- 25113543
TI - Molecular characterization of rice sphingosine-1-phosphate lyase gene OsSPL1 and
functional analysis of its role in disease resistance response.
AB - KEY MESSAGE: Our results indicate that overexpression of OsSPL1 in transgenic
tobacco plants attenuated disease resistance and facilitated programmed cell
death. Long-chain base phosphates including sphingosine-1-phosphate have been
shown to act as signaling mediators in regulating programmed cell death (PCD) and
stress responses in mammals. In the present study, we characterized a rice gene
OsSPL1, encoding a putative sphingosine-1-phosphate lyase that is involved in
metabolism of sphingosine-1-phosphate. Expression of OsSPL1 was down-regulated in
rice plants after treatments with salicylic acid, benzothiadiazole and 1-amino
cyclopropane-1-carboxylic acid, but was induced by infection with a virulent
strain of Magnaporthe oryzae, the causal agent of rice blast disease. Transgenic
tobacco lines with overexpression of OsSPL1 were generated and analyzed for the
possible role of OsSPL1 in disease resistance response and PCD. The OsSPL1
overexpressing tobacco plants displayed increased susceptibility to infection of
Pseudomonas syringae pv. tabaci (Pst), the causal agent of wildfire disease,
showing severity of disease symptom and bacterial titers in inoculated leaves,
and attenuated pathogen-induced expression of PR genes after infection of Pst as
compared to the wild-type and vector-transformed plants. Higher level of cell
death, as revealed by dead cell staining, leakage of electrolyte and expression
of hypersensitive response indicator genes, was observed in the OsSPL1
overexpressing plants after treatment with fumonisin B1, a fungal toxin that
induces PCD in plants. Our results suggest that OsSPL1 has different functions in
regulating disease resistance response and PCD in plants.
PMID- 25113546
TI - Single-cell transcriptome in the identification of disease biomarkers:
opportunities and challenges.
AB - Single cell transcriptome defined as the entire RNA or polyadenylated products of
RNA polymerase II on a cell can describe the gene regulation networks responsible
for physiological functions, behaviours, and phenotypes in response to signals
and microenvironmental changes. Single cell transcriptome/sequencing has the
special power to investigate small groups of differentiating cells, circulating
tumour cells, or tissue stem cells. A large number of factors may influence the
extent of single-cell heterogeneity within a system. It is the opportunity that
the single-cell sequencing can be used for the identification of genetic changes
in rare cells, e.g. cancer and tissue stem cells, in clinical samples. The
methodologies of single-cell sequencing have been improved and developed with the
increase of the understanding and attention. The clinical research and
application of the single cell sequencing analysis are expected to identify and
validate disease-specific biomarkers, network biomarkers, dynamic network
biomarkers. The single cell research and value will be also dependent upon the
understanding of genomic heterogeneity, planning and design of study protocol,
representative of selected and targeted cells, and sensitivity and repeatability
of the methodology. The single cell sequencing can be used to develop new
diagnostics, monitor disease progresses, measure responses to therapies, and
predict the prognosis of patients, although there are still a large number of
challenges and difficulties to be faced. It would be more values and
specificities of the single cell sequencing to integrate with the function of
cells, organs, and systems of the body, the clinical phenotypes of patients, and
the description of clinical bioinformatics.
PMID- 25113544
TI - Molecular and physiological stages of priming: how plants prepare for
environmental challenges.
AB - Being sessile organisms, plants must respond to various challenges in the
environment. The priming process consists of three clear stages. The first stage
includes all the cellular changes in the absence of the challenge so-called pre
challenge priming stage. These changes are expected to be rather subtle,
affecting the preparation of the plant to properly manage subsequent responses to
pathogens with no major fitness costs. Most of the research that has been
conducted at this stage has been dedicated to the study of changes in gene
expression and protein phosphorylation. However, the metabolic changes that occur
during the pre-challenge priming stage are poorly understood. The second stage
affects the early to late stages of the defence response, which occurs after the
interaction with a pathogen has been established. Most studies involving priming
are dedicated to the molecular events that take place during this stage. Most
studies have shown that defence priming is strongly hormonally regulated;
however, there is also evidence of the involvement of phenolic derivative
compounds and many other secondary metabolites, leading to stronger and faster
plant responses. The third priming phase ranges from long lasting defence priming
to trans-generational acquired resistance. Long-term metabolic transitions, that
occur in the offspring of primed plants, remain to be elucidated. Here we review
existing information in the literature that relates to the metabolic changes that
occur during all three defence priming stages and highlight the metabolic
transitions that are associated with the stimulation of priming and the
characteristics of the pathogens whenever possible.
PMID- 25113548
TI - [Concordance between central venous and arterial blood gases in post-surgical
myocardial revascularization patients in stable condition].
AB - OBJECTIVE: The concordance between the parameters of arterial and central venous
blood gases has not been defined yet. We studied the concordance between both
parameters in post-surgical myocardial revascularization patients in stable
condition. METHODS: Consecutive subjects were studied in a cross-sectional
design. The position of the central venous catheter was performed and
simultaneously we obtained arterial and central venous blood samples prior to
discharge from the intensive care unit. Data are expressed according to Bland
Altman statistical method and the intraclass correlation coefficient. Statistical
result was accepted at P<.05. RESULTS: Two hundred and six samples were studied
of 103 post-surgical patients, pH and lactate had a mean difference (limits of
agreement) 0.029+/-0.048 (-0018, 0.077) and -0.12+/-0.22 (-0.57, 0.33)
respectively. The magnitude of the intraclass correlation coefficient was 0.904
and 0.943 respectively. The values related to oxygen pressure were 27.86+/-6.08
(15.9, 39.8) and oxygen saturation 33.02+/-6.13 (21, 45), with magnitude of 0.258
and 0.418 respectively. CONCLUSION: The best matching parameters between arterial
and central venous blood samples were pH and lactate.
PMID- 25113549
TI - Preparation, biodistribution, and scintigraphic evaluation of (99m)Tc
clindamycin: an infection imaging agent.
AB - Bacterial infection is found to be the cause of death throughout the world.
Nuclear medicine imaging with the help of radiopharmaceuticals has great
potential for treating infections. In the present work, clindamycin, a
lincosamide antibiotic, was labeled with technetium-99 m (~380 MBq). Clindamycin
has been proven to be efficient for treating serious infections caused by
bacteria such as Staphylococcus aureus. Quality control, characterization,
biodistribution, and scintigraphy of radiolabeled clindamycin were done, and
labeling efficiency was determined by ascending paper chromatography. More than
95 % labeling efficiency with technetium-99 m ((99m)Tc) was achieved at pH 6-7
while using 2.5-3 MUg SnCl2 . H2O as a reducing agent and 100 MUg of ligand at
room temperature. The characterization of the compound was performed by using
electrophoresis, HPLC and shake flask assay. Electrophoresis indicates the
neutral behavior of (99m)Tc-clindamycin. HPLC analysis confirms the single specie
of the labeled compound, while shake flask assay confirms high lipophilicity. The
biodistribution studies of (99m)Tc-clindamycin were performed Sprague Dawley rats
bearing bacterial infection. Scintigraphy and biodistribution studies showed a
high uptake of (99m)Tc-clindamycin in the liver, heart, lung, and stomach as well
as at S. aureus-infected sites in rabbits.
PMID- 25113547
TI - Digging a little deeper: the stages of invadopodium formation and maturation.
AB - Invadopodia are actin-rich protrusions that degrade the extracellular matrix and
are required for penetration through the basement membrane, stromal invasion and
intravasation. Invadopodia are enriched in actin regulators, such as cortactin,
cofilin, N-WASp, Arp2/3 and fascin. Much of the work to date has centered around
identifying the proteins involved in regulating actin polymerization and matrix
degradation. Recently, there have been significant advances in characterization
of the very early stages of invadopodium precursor assembly and the role of
adhesion proteins, such as beta1 integrin, talin, FAK and Hic-5, in promoting
invadopodium maturation. This review summarizes these findings in the context of
our current model of invadopodial function and highlights some of the important
unanswered questions in the field.
PMID- 25113550
TI - Bioremediation of distillery sludge into soil-enriching material through
vermicomposting with the help of Eisenia fetida.
AB - The aim of the present study was bioremediation of distillery sludge into a soil
enriching material. It was mixed with a complementary waste, cattle dung, and
subjected to vermicomposting with (V) and without (T, control) Eisenia fetida in
the ratio of 0:100 % (V1, T1), 10:90 (V2, T2), 25:75 (V3, T3), 50:50 (V4, T4),
75:25 (V5, T5) and 100:0 % (V6, T6), respectively. Survival rate, growth rate,
onset of maturity, cocoon production and population build-up increased with
increasing ratio of cattle dung. Maximum mortality of earthworm was observed in
V6 mixture. On the basis of response surface design, the concentration of sludge
giving highest number of worms, cocoons and hatchlings came out to be 21.11,
24.51 and 17.19 %, respectively. Nitrogen, phosphorus, sodium and pH increased
during vermicomposting but decreased in the products without earthworm and there
was increase in the contents of transition metals in the products of both the
techniques. However, organic carbon, electrical conductivity and potassium showed
an opposite trend.
PMID- 25113551
TI - Impact of xylan on synergistic effects of xylanases and cellulases in enzymatic
hydrolysis of lignocelluloses.
AB - Supplementation of xylanase (XYL) has been found to synergistically improve the
performance of cellulases (CEL) in the hydrolysis of lignocelluloses. However,
the effect of xylan on the synergistic effects of XYL and CEL is still unclear.
In this work, the effect of xylan on the synergy between CEL and XYL was
investigated. Xylan content in corn stover was generally a good indicator of the
degree of the synergism between CEL and XYL. Strongest synergism was observed in
the hydrolysis of cellulose in corn stover with the highest xylan contents. A
more evident synergistic effect of CEL in xylan hydrolysis was observed in the
substrates with low original xylan content. It was also found that the ratio of
cellulose to xylan in substrates correlated to the synergism between the two
types of enzymes. The results indicated that supplementation of XYL with CEL was
most effective in the hydrolysis of corn stover with the highest xylan content.
For efficient enzymatic hydrolysis of lignocelluloses, both cellulases and
xylanase were important because cellulose and xylan coved each other and these
enzymes could improve their performance each other in the hydrolysis of cellulose
and xylan in lignocelluloses.
PMID- 25113552
TI - Fluidized bed layer-by-layer microcapsule formation.
AB - Polymer microcapsules can be used as bioreactors and artificial cells; however,
preparation methods for cell-like microcapsules are typically time-consuming, low
yielding, and/or involve custom microfluidics. Here, we introduce a rapid (~30
min per batch, eight layers), scalable (up to 500 mg of templates), and efficient
(98% yield) microcapsule preparation technique utilizing a fluidized bed for the
layer-by-layer (LbL) assembly of polymers, and we investigate the parameters that
govern the formation of robust capsules. Fluidization in water was possible for
particles of comparable diameter to mammalian cells (>5 MUm), with the
experimental flow rates necessary for fluidization matching well with the
theoretical values. Important variables for polymer film deposition and capsule
formation were the concentration of polymer solution and the molecular weight of
the polymer, while the volume of the polymer solution had a negligible impact. In
combination, increasing the polymer molecular weight and polymer solution
concentration resulted in improved film deposition and the formation of robust
microcapsules. The resultant polymer microcapsules had a thickness of ~5.5 nm per
bilayer, which is in close agreement with conventionally prepared (quiescent
(nonflow) adsorption/centrifugation/wash) LbL capsules. The technique reported
herein provides a new way to rapidly generate microcapsules (approximately 8
times quicker than the conventional means), while being also amenable to scale-up
and mass production.
PMID- 25113553
TI - Contraceptive confidence and timing of first birth in Moldova: an event history
analysis of retrospective data.
AB - OBJECTIVES: To test the contraceptive confidence hypothesis in a modern context.
The hypothesis is that women using effective or modern contraceptive methods have
increased contraceptive confidence and hence a shorter interval between marriage
and first birth than users of ineffective or traditional methods. We extend the
hypothesis to incorporate the role of abortion, arguing that it acts as a
substitute for contraception in the study context. SETTING: Moldova, a country in
South-East Europe. Moldova exhibits high use of traditional contraceptive methods
and abortion compared with other European countries. PARTICIPANTS: Data are from
a secondary analysis of the 2005 Moldovan Demographic and Health Survey, a
nationally representative sample survey. 5377 unmarried women were selected.
PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome measure was the interval
between marriage and first birth. This was modelled using a piecewise-constant
hazard regression, with abortion and contraceptive method types as primary
variables along with relevant sociodemographic controls. RESULTS: Women with high
contraceptive confidence (modern method users) have a higher cumulative hazard of
first birth 36 months following marriage (0.88 (0.87 to 0.89)) compared with
women with low contraceptive confidence (traditional method users, cumulative
hazard: 0.85 (0.84 to 0.85)). This is consistent with the contraceptive
confidence hypothesis. There is a higher cumulative hazard of first birth among
women with low (0.80 (0.79 to 0.80)) and moderate abortion propensities (0.76
(0.75 to 0.77)) than women with no abortion propensity (0.73 (0.72 to 0.74)) 24
months after marriage. CONCLUSIONS: Effective contraceptive use tends to increase
contraceptive confidence and is associated with a shorter interval between
marriage and first birth. Increased use of abortion also tends to increase
contraceptive confidence and shorten birth duration, although this effect is non
linear-women with a very high use of abortion tend to have lengthy intervals
between marriage and first birth.
PMID- 25113554
TI - Long-term follow-up results in patients undergoing percutaneous coronary
intervention (PCI) with drug-eluting stents: results from a single high-volume
PCI centre.
AB - OBJECTIVE: To assess both short-term and long-term prognosis in consecutive
patients with coronary heart disease treated with drug-eluting stents in a high
volume percutaneous coronary intervention (PCI) centre. DESIGN: Observational
cohort study. SETTING: A hospital in the Henan province, China, between 2009 and
2011. PARTICIPANTS: A total of 2533 patients were enrolled. Patients with ST
elevation myocardial infarction (STEMI) treated with urgent PCI accounted for
3.9% of cases; patients with STEMI treated with delayed PCI accounted for 20.5%
of cases; patients with stable angina accounted for 16.5% of cases; and patients
with non-ST elevation acute coronary syndrome (NSTE-ACS) accounted for 58.6% of
cases. PRIMARY OUTCOMES: Death, major adverse cardiac and cerebrovascular events
(MACCE: death/myocardial infarction/stroke), and target vessel revascularisation.
RESULTS: Follow-up after a median of 29.8 months was obtained for 2533 patients
(92.6%). The mortality rate during hospitalisation was highest in the urgent PCI
group (p<0.001). During follow-up, although the incidences of death and MACCE
were highest in the urgent PCI group, no significant differences were observed
among the different groups. The incidences of cardiac death and myocardial
infarction were significantly higher in the paclitaxel-eluting stent (PES) group
than in the sirolimus-eluting stent (SES) group. Independent predictors of death
during follow-up were age, left ventricular ejection function <40%, diabetes
mellitus, prior coronary artery bypass graft and chronic total occlusion.
CONCLUSIONS: PCI patients with STEMI had the worst hospital and long-term
prognosis. The mortality rate after hospital increased markedly in patients with
NSTE-ACS. SESs seem to be more effective than PESs.
PMID- 25113555
TI - Effects of the First Line Diabetes Care (FiLDCare) self-management education and
support project on knowledge, attitudes, perceptions, self-management practices
and glycaemic control: a quasi-experimental study conducted in the Northern
Philippines.
AB - OBJECTIVES: To investigate the effects of implementing a context-adapted diabetes
self-management education and support (DSME/S) project based on chronic care
models in the Philippines, on knowledge, attitudes, self-management practices,
adiposity/obesity and glycaemia of people with diabetes. DESIGN: Prospective
quasi-experimental before-after study. PARTICIPANTS: 203 people with type 2
diabetes mellitus from two local government units in the Northern Philippines
fulfilling set criteria. OUTCOME MEASURES: Context-adapted DSME/S was given to a
cohort of people with diabetes by trained pre-existing local government
healthcare personnel. Changes in knowledge, attitudes and self-management
practices, body mass index, waist circumference, waist-hip ratio (WHR) and
glycosylated haemoglobin (HbA1c) were measured 1 year after full project
implementation. Non-parametric and parametric descriptive and inferential
statistics including logistic regression analysis were done. RESULTS: Complete
data were collected from 164 participants. Improvements in glycaemia, waist
circumference, WHR, knowledge, some attitudes, adherence to medications and
exercise, and an increase in fear of diabetes were significant. Reductions in
HbA1c, regardless of level of control, were noted in 60.4%. Significant increase
in knowledge (p<0.001), positive attitude (p=0.013), perceived ability to control
blood glucose (p=0.004) and adherence to medications (p=0.001) were noted among
those whose glycaemia improved. Significant differences between the subgroups
whose HbA1c improved and those whose HbA1c deteriorated include male gender
(p=0.042), shorter duration of diabetes (p=0.001) and increased perceived ability
to control blood glucose (p=0.042). Significant correlates to improved glycaemia
were male gender (OR=2.655; p=0.034), duration of diabetes >10 years (OR=0.214;
p=0.003) and fear of diabetes (OR=0.490; p=0.048). CONCLUSIONS: Context-adapted
DSME/S introduced in resource-constrained settings and making use of established
human resources for health may improve knowledge, attitudes, self-management
practices and glycaemia of recipients. Further investigations on addressing fear
of diabetes and tailoring DSME/S to females with diabetes and those who have had
diabetes for a longer period of time may help improve glycaemia.
PMID- 25113556
TI - Assessing the feasibility of a randomised, double-blinded, placebo-controlled
trial to investigate the role of intraperitoneal ropivacaine in gastric bypass
surgery: a protocol.
AB - INTRODUCTION: Postoperative pain control remains a major challenge for surgical
procedures, including laparoscopic gastric bypass. Pain management is
particularly relevant in obese patients who experience a higher number of
cardiovascular and pulmonary events. Effective pain management may reduce their
risk of serious postoperative complication, such as deep vein thrombosis and
pulmonary emboli. The objective of this study is to evaluate the efficacy of
intraperitoneal local anaesthetic, ropivacaine, to reduce postoperative pain in
patients undergoing laparoscopic Roux-en-Y gastric bypass. METHODS AND ANALYSIS:
A randomised controlled trial will be conducted to compare intraperitoneal
ropivacaine (intervention) versus normal saline (placebo) in 120 adult patients
undergoing bariatric bypass surgery. Ropivacaine will be infused over the
oesophageal hiatus and throughout the abdomen. Patients in the control arm will
undergo the same treatment with normal saline. The primary end point will be
postoperative pain at 1, 2 and 4 h postoperatively. Pain measurements will then
occur every 4 h for 24 h and every 8 h until discharge. Secondary end points will
include opioid use, peak expiratory flow, 6 min walk distance and quality of life
assessed in the immediate postoperative period. Intention-to-treat analysis will
be used and repeated measures will be analysed using mixed modelling approach.
Post-hoc pairwise comparison of the treatment groups at different time points
will be carried out using multiple comparisons with adjustment to the type 1
error. Results of the study will inform the feasibility of recruitment and inform
sample size of a larger definitive randomised trial to evaluate the effectiveness
of intraperitoneal ropivacaine. ETHICS AND DISSEMINATION: This study has been
approved by the Ottawa Health Science Network Research Ethics Board and Health
Canada in April 2014. The findings of the study will be disseminated through
national and international conferences and peer-reviewed journals. TRIAL
REGISTRATION NUMBER: Clinicaltrial.gov NCT02154763.
PMID- 25113557
TI - Pneumococcal colonisation density: a new marker for disease severity in HIV
infected adults with pneumonia.
AB - OBJECTIVE: A high genomic load of Pneumococcus from blood or cerebrospinal fluid
has been associated with increased mortality. We aimed to analyse whether
nasopharyngeal colonisation density in HIV-infected patients with community
acquired pneumonia (CAP) is associated with markers of disease severity or poor
outcome. METHODS: Quantitative lytA real-time PCR was performed on nasopharyngeal
swabs in HIV-infected South African adults hospitalised for acute CAP at Chris
Hani Baragwanath Hospital, Soweto, South Africa. Pneumonia aetiology was
considered pneumococcal if any sputum culture or Gram stain, urinary pneumococcal
C-polysaccharide-based antigen, blood culture or whole blood lytA real-time PCR
revealed pneumococci. RESULTS: There was a moderate correlation between the mean
nasopharyngeal colonisation densities and increasing CURB65 scores among all
cause patients with pneumonia (Spearman correlation coefficient r=0.15, p=0.06)
or with the Pitt bacteraemia score among patients with pneumococcal bacteraemia
(p=0.63). In patients with pneumococcal pneumonia, nasopharyngeal pneumococcal
colonisation density was higher among non-survivors than survivors (7.7 vs 6.1
log10 copies/mL, respectively, p=0.02) and among those who had pneumococci
identified from blood cultures and/or by whole blood lytA real-time PCR than
those with non-bacteraemic pneumococcal pneumonia (6.6 vs 5.6 log10 copies/mL,
p=0.03). Nasopharyngeal colonisation density correlated positively with the
biomarkers procalcitonin (Spearman correlation coefficient r=0.37, p<0.0001),
proadrenomedullin (r=0.39, p=0.008) and copeptin (r=0.30, p=0.01). CONCLUSIONS:
In addition to its previously reported role as a diagnostic tool for pneumococcal
pneumonia, quantitative nasopharyngeal colonisation density also correlates with
mortality and prognostic biomarkers. It may also be useful as a severity marker
for pneumococcal pneumonia in HIV-infected adults.
PMID- 25113558
TI - PERK-dependent activation of JAK1 and STAT3 contributes to endoplasmic reticulum
stress-induced inflammation.
AB - Neuroinflammation and endoplasmic reticulum (ER) stress are associated with many
neurological diseases. Here, we have examined the interaction between ER stress
and JAK/STAT-dependent inflammation in glial cells. We show that ER stress is
present in the central nervous system (CNS) concomitant with inflammation and
astrogliosis in the multiple sclerosis (MS) mouse model of experimental
autoimmune encephalomyelitis (EAE). Astrocytes do not easily succumb to ER stress
but rather activate an inflammatory program involving activation of STAT3 in a
JAK1-dependent fashion. ER stress-induced activation of the JAK1/STAT3 axis leads
to expression of interleukin 6 (IL-6) and several chemokines. Moreover, the
activation of STAT3 signaling is dependent on PERK, a central component of the ER
stress response, which we show is phosphorylated by JAK1. Disruption of PERK
abrogates ER stress-induced activation of STAT3 and subsequent gene expression.
Additionally, ER-stressed astrocytes, via paracrine signaling, can stimulate
activation of microglia, leading to production of IL-6 and oncostatin M (OSM).
These IL-6 cytokines can then synergize with ER stress in astrocytes to drive
inflammation. Together, this work describes a new PERK/JAK1/STAT3 signaling
pathway that elicits a feed-forward inflammatory loop involving astrocytes and
microglia to drive neuroinflammation, which may be relevant in diseases such as
MS.
PMID- 25113561
TI - Plakophilin-2 promotes activation of epidermal growth factor receptor.
AB - While growth factor-driven dimerization of receptor tyrosine kinases (RTKs) is a
simple and intuitive mechanism of activating RTKs, K.-I. Arimoto et al. (Mol.
Cell. Biol. 34:3843-3854, 2014, doi:10.1128/MCB.00758-14) describe a novel means
of promoting the activity of RTKs. Namely, plakophilin-2 (PKP2) associates with
the epidermal growth factor receptor (EGFR) and enhances its ligand-dependent and
ligand-independent activity. This discovery suggests that antagonizing PKP2 may
be a new therapeutic opportunity to combat tumors in which activation of EGFR
contributes to pathogenesis.
PMID- 25113559
TI - Regulation of the protocadherin Celsr3 gene and its role in globus pallidus
development and connectivity.
AB - The globus pallidus (GP) is a central component of basal ganglia whose
malfunctions cause a variety of neuropsychiatric disorders as well as cognitive
impairments in neurodegenerative diseases such as Parkinson's disease. Here we
report that the protocadherin gene Celsr3 is regulated by the insulator CCCTC
binding factor (CTCF) and the repressor neuron-restrictive silencer factor (NRSF,
also known as REST) and is required for the development and connectivity of GP.
Specifically, CTCF/cohesin and NRSF inhibit the expression of Celsr3 through
specific binding to its promoter. In addition, we found that the Celsr3 promoter
interacts with CTCF/cohesin-occupied neighboring promoters. In Celsr3 knockout
mice, we found that the ventral GP is occupied by aberrant calbindin-positive
cholinergic neurons ectopic from the nucleus basalis of Meynert. Furthermore, the
guidepost cells for thalamocortical axonal development are missing in the caudal
GP. Finally, axonal connections of GP with striatum, subthalamic nucleus,
substantia nigra, and raphe are compromised. These data reveal the essential role
of Celsr3 in GP development in the basal forebrain and shed light on the
mechanisms of the axonal defects caused by the Celsr3 deletion.
PMID- 25113560
TI - Plakophilin-2 promotes tumor development by enhancing ligand-dependent and
independent epidermal growth factor receptor dimerization and activation.
AB - Epidermal growth factor (EGF) receptor (EGFR) has been implicated in tumor
development and invasion. Dimerization and autophosphorylation of EGFR are the
critical events for EGFR activation. However, the regulation of EGF-dependent and
EGF-independent dimerization and phosphorylation of EGFR has not been fully
understood. Here, we report that cytoplasmic protein plakophilin-2 (PKP2) is a
novel positive regulator of EGFR signaling. PKP2 specifically interacts with EGFR
via its N-terminal head domain. Increased PKP2 expression enhances EGF-dependent
and EGF-independent EGFR dimerization and phosphorylation. Moreover, PKP2
knockdown reduces EGFR phosphorylation and attenuates EGFR-mediated signal
activation, resulting in a significant decrease in proliferation and migration of
cancer cells and tumor development. Our results indicate that PKP2 is a novel
activator of the EGFR signaling pathway and a potential new drug target for
inhibiting tumor growth.
PMID- 25113563
TI - Special issue of BJP on nanomedicine.
PMID- 25113562
TI - Piwil2 inhibits keratin 8 degradation through promoting p38-induced
phosphorylation to resist Fas-mediated apoptosis.
AB - The piwi-like 2 (piwil2) gene is widely expressed in tumors and protects cells
from apoptosis induced by a variety of stress stimuli. However, the role of
Piwil2 in Fas-mediated apoptosis remains unknown. Here, we present evidence that
Piwil2 inhibits Fas-mediated apoptosis. By a bacterial two-hybrid screening, we
identify a new Piwil2-interacting partner, keratin 8 (K8), a major intermediate
filament protein protecting the cell from Fas-mediated apoptosis. Our results
show that Piwil2 binds to K8 and p38 through its PIWI domain and forms a
Piwil2/K8/P38 triple protein-protein complex. Thus, Piwil2 increases the
phosphorylation level of K8 Ser-73 and then inhibits ubiquitin-mediated
degradation of K8. As a result, the knockdown of Piwil2 increases the Fas protein
level at the membrane. In addition to our previous finding that Piwil2 inhibits
the expression of p53 through the Src/STAT3 pathway, here we demonstrate that
Piwil2 represses p53 phosphorylation through p38. Our present study indicates
that Piwil2 plays a role in Fas-mediated apoptosis for the first time and also
can affect p53 phosphorylation in tumor cells, revealing a novel mechanism of
Piwil2 in apoptosis, and supports that Piwil2 plays an active role in
tumorigenesis.
PMID- 25113564
TI - Human fibrocytic myeloid-derived suppressor cells express IDO and promote
tolerance via Treg-cell expansion.
AB - By restraining T-cell activation and promoting Treg-cell expansion, myeloid
derived suppressor cells (MDSCs) and tolerogenic DCs can control self-reactive
and antigraft effector T cells in autoimmunity and transplantation. Their
therapeutic use and characterization, however, is limited by their scarce
availability in the peripheral blood of tumor-free donors. In the present study,
we describe and characterize a novel population of human myeloid suppressor
cells, named fibrocytic MDSC, which are differentiated from umbilical cord blood
precursors by 4-day culture with FDA-approved cytokines (recombinant human-GM-CSF
and recombinant human-G-CSF). This MDSC subset, characterized by the expression
of MDSC-, DC-, and fibrocyte-associated markers, promotes Treg-cell expansion and
induces normoglycemia in a xenogeneic mouse model of Type 1 diabetes. In order to
exert their protolerogenic function, fibrocytic MDSCs require direct contact with
activated T cells, which leads to the production and secretion of IDO. This new
myeloid subset may have an important role in the in vitro and in vivo production
of Treg cells for the treatment of autoimmune diseases, and in either the
prevention or control of allograft rejection.
PMID- 25113565
TI - Genistein attenuates choroidal neovascularization.
AB - Genistein is a dietary-derived flavonoid abundantly present in soybeans and known
to possess various biological effects including anti-inflammation and anti
angiogenic activity. To investigate the effects of genistein on intraocular
neovascularization, we used an animal model of laser-induced choroidal
neovascularization (CNV). Male C57BL/6J mice were treated in accordance with the
ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. CNV was
induced by laser photocoagulation. The animals were fed a mixture diet containing
0.5% genistein or a control diet ad libitum for 7 days before laser
photocoagulation and the treatment was continued until the end of the study.
Seven days after laser injury, the size of CNV lesions was quantified. Retinal
pigment epithelium (RPE)-choroid complex was also harvested 1 or 3 days after
laser injury and the level of monocyte chemoattractant protein (MCP)-1,
intercellular adhesion molecule (ICAM)-1, and matrix metalloproteinase (MMP)-9
were measured by enzyme-linked immunosorbent assay. Expression levels of Ets-1
and F4/80 were examined by real-time PCR. A significant decrease in CNV size was
observed in animals treated with genistein (15441.9+/-1511.8 MUm(2)) compared to
control mice (21074.0+/-1940.7MUm(2), P<.05). Genistein significantly reduced the
protein level of MCP-1, ICAM-1, and MMP-9 in the RPE-choroid complex (P<.05). In
addition, genistein suppressed the expression levels of Ets-1 and F4/80 (P<.05).
The current data indicate the anti-angiogenic property of genistein during CNV
formation.
PMID- 25113566
TI - What can genes tell us about the relationship between education and health?
AB - We use genome wide data from respondents of the Health and Retirement Study (HRS)
to evaluate the possibility that common genetic influences are associated with
education and three health outcomes: depression, self-rated health, and body mass
index. We use a total of 1.7 million single nucleotide polymorphisms obtained
from the Illumina HumanOmni2.5-4v1 chip from 4233 non-Hispanic white respondents
to characterize genetic similarities among unrelated persons in the HRS. We then
used the Genome Wide Complex Trait Analysis (GCTA) toolkit, to estimate
univariate and bivariate heritability. We provide evidence that education (h(2) =
0.33), BMI (h(2) = 0.43), depression (h(2) = 0.19), and self-rated health (h(2) =
0.18) are all moderately heritable phenotypes. We also provide evidence that some
of the correlation between depression and education as well as self-rated health
and education is due to common genetic factors associated with one or both
traits. We find no evidence that the correlation between education and BMI is
influenced by common genetic factors.
PMID- 25113568
TI - Adding insult to injury: The development of psychosocial stress in Ontario wind
turbine communities.
AB - Though historically dismissed as not-in-my-backyard (NIMBY) attitudes, reports of
psychosocial stress linked to wind energy developments have emerged in Ontario,
Canada. While the debate and rhetoric intensify concerning whether wind turbines
'actually' cause 'health' effects, less sincere attention has been given to the
lived experience and mental well-being of those near turbines. Drawing on
theories of environmental stress, this grounded theory, mixed-method (n = 26
interviews; n = 152 questionnaires) study of two communities in 2011 and 2012
traces how and why some wind turbine community residents suffer substantial
changes to quality of life, develop negative perceptions of 'the other' and in
some cases, experience intra-community conflict. Policy-related forces, along
with existing community relationships may help explain much of these differences
between communities. We suggest a move beyond debating simply whether or not
'annoyance' represents a 'health impact' and instead focus on ways to minimize
and attenuate these feelings of threat (risk) and stress at the community level.
PMID- 25113567
TI - When does education matter? The protective effect of education for cohorts
graduating in bad times.
AB - Using Eurobarometer data, we document large variation across European countries
in education gradients in income, self-reported health, life satisfaction,
obesity, smoking and drinking. While this variation has been documented
previously, the reasons why the effect of education on income, health and health
behaviors varies is not well understood. We build on previous literature
documenting that cohorts graduating in bad times have lower wages and poorer
health for many years after graduation, compared to those graduating in good
times. We investigate whether more educated individuals suffer smaller income and
health losses as a result of poor labor market conditions upon labor market
entry. We confirm that a higher unemployment rate at graduation is associated
with lower income, lower life satisfaction, greater obesity, more smoking and
drinking later in life. Further, education plays a protective role for these
outcomes, especially when unemployment rates are high: the losses associated with
poor labor market outcomes are substantially lower for more educated individuals.
Variation in unemployment rates upon graduation can potentially explain a large
fraction of the variance in gradients across different countries.
PMID- 25113570
TI - Recreational participation and the development of social competence in preschool
aged children with disabilities: a cross-sectional study.
AB - PURPOSE: To explore the association between participation and social competence
for preschool aged children with and without disabilities. METHODS: The sample
was drawn from the Longitudinal Study of Australian Children (n = 4983) which
included children aged 4-5 years reported to have hearing problems (n = 164),
vision problems (n = 146) and other physical disabilities (n = 114). Chi-square,
correlation and logistic regression analyses were used to describe the
participation and social competence of children with and without these
conditions, as well as examine the association between these constructs. RESULTS:
Children with disabilities had similar levels of participation but lower social
competence than children without these disabilities. Further analyses revealed a
small negative correlation between the two variables (ranging from -0.120 to
0.300 for the three groups) and that children who have low participation are more
likely to have abnormal levels of social competence than children with higher
participation. CONCLUSIONS: The association between participation and social
competence may not be as strong for this age group as anticipated in the
literature, additional factors may be influential. Examination of the social
competence scores identified two factors which may assist in explaining the
variance in scores: (1) the experience of disability and (2) the quality of
interactions. IMPLICATIONS FOR REHABILITATION: Children with disabilities who
participate in similar activities to their typically developing peers may not
necessarily develop commensurate levels of social competence. As well as focusing
on increasing the participation of children in activities other factors that may
have a stronger influence on social competence should be considered, such as
supporting (1) the social experience of disability and (2) the quality of
interactions that children with disabilities experience.
PMID- 25113571
TI - A day in the life of older people in a rehabilitation setting: an observational
study.
AB - PURPOSE: Nurses' contribution during inpatient rehabilitation is well documented.
However, despite being the largest professional group in this setting, the
specialty of rehabilitation nursing is poorly recognised. This article reports on
the first of a four-phase study that aimed to clarify and develop the nursing
contribution to inpatient rehabilitation for older persons. The aim of this study
was to identify activity patterns and time use during daytime and evenings of
older adult patients undergoing inpatient rehabilitation. METHODS: Direct
observation using behavioural modelling was undertaken of a convenience sample of
37 older people undergoing inpatient rehabilitation in a specialist unit of a
large tertiary hospital in New Zealand. The primary outcome was the observation
of meaningful activity. Binomial logistic regression was used to study the
association between relevant variables. FINDINGS: Meaningful activity was most
likely to involve walking without assistance and to occur 08:00 to 14:00 h and
16:00 to 21:00 h during weekdays. Patients were more likely to receive treatment
during the weekend. Irrespective of time, registered nurses were the health
professionals most often present with patients. CONCLUSIONS: There is likely to
be unrealised opportunities for registered nurses to support improved
rehabilitation outcomes. Registered nurses' involvement in rehabilitation needs
to be actively optimised. IMPLICATIONS FOR REHABILITATION: Nurses' engagement
with older adults in rehabilitation settings is likely to be substantial, placing
them as key members of the rehabilitation team. Nurses make a pivotal
contribution to inpatient rehabilitation based on specialised knowledge and
skills but this contribution is not well understood. Opportunities are likely, at
times when allied health professionals are less often present, e.g. evenings and
weekends, for registered nurses to more intentionally overlap rehabilitation
activities with other care requirements.
PMID- 25113572
TI - Supporting the Loewenstein occupational therapy cognitive assessment using
distributed user interfaces.
AB - PURPOSE: Improve the quantity and quality of information obtained from
traditional Loewenstein Occupational Therapy Cognitive Assessment Battery systems
to monitor the evolution of patients' rehabilitation process as well as to
compare different rehabilitation therapies. METHODS: The system replaces
traditional artefacts with virtual versions of them to take advantage of cutting
edge interaction technology. The system is defined as a Distributed User
Interface (DUI) supported by a display ecosystem, including mobile devices as
well as multi-touch surfaces. Due to the heterogeneity of the devices involved in
the system, the software technology is based on a client-server architecture
using the Web as the software platform. RESULTS: The system provides therapists
with information that is not available (or it is very difficult to gather) using
traditional technologies (i.e. response time measurements, object tracking,
information storage and retrieval facilities, etc.). CONCLUSIONS: The use of DUIs
allows therapists to gather information that is unavailable using traditional
assessment methods as well as adapt the system to patients' profile to increase
the range of patients that are able to take this assessment. Implications for
Rehabilitation Using a Distributed User Interface environment to carry out LOTCAs
improves the quality of the information gathered during the rehabilitation
assessment. This system captures physical data regarding patient's interaction
during the assessment to improve the rehabilitation process analysis. Allows
professionals to adapt the assessment procedure to create different versions
according to patients' profile. Improves the availability of patients' profile
information to therapists to adapt the assessment procedure.
PMID- 25113573
TI - A stair-climbing test for measuring mechanical efficiency of ambulation in adults
with chronic stroke.
AB - PURPOSE: Mechanical efficiency can assess motor performance in individuals with
physical disabilities. The purpose was to determine the utility of predicting it
from heart rate (HR) during a self-paced stair-climbing test in adults with
chronic hemiparesis after stroke and to determine the minimal detectable change
of net mechanical efficiency (MEnet) measured by this exercise. METHODS: First,
15 subjects with chronic hemiparesis participated in a validation study (A) and
then 28 took part in a repeatability study (B). In study A the MEnet was
calculated from external work and oxygen uptake above rest (dVO2), as directly
measured and as predicted from body weight and increase in heart rate (dHR). In
study B, predicted dVO2 was used to obtain MEnet for duplicate stair-climbing
tests (T1, T2) with >30 min rest between. RESULTS: Measured MEnet was closely
related to predicted MEnet (r = 0.97, p < 0.001). In study B predicted MEnet for
T2 and T1 were closely related (r = 0.91, ICC = 0.90). CONCLUSION: With a minimal
detectable change of 0.6% (0.053 of average MEnet score of 10.4%), MEnet values
from the stair-climbing test seem sufficiently meaningful to estimate ambulatory
ability and its changes with interventions or walking aids in adults with
hemiparesis. IMPLICATIONS FOR REHABILITATION: Ambulatory ability can be estimated
from mechanical efficiency, obtained from a 5-min stair-climbing test utilizing a
4-step stair, to measure external work, and the change in heart rate above rest
to estimate the metabolic cost of the task. A change of > 0.6% in mechanical
efficiency by this stair-climbing test indicates a significant change in
ambulatory ability of persons with hemiparesis.
PMID- 25113574
TI - Serratus anterior muscle pedicle as the recipient site in DIEP flap transfer for
breast reconstruction: why not the first choice?
PMID- 25113575
TI - A structural and spectroscopic investigation of octahedral platinum
bis(dithiolene)phosphine complexes: platinum dithiolene internal redox chemistry
induced by phosphine association.
AB - The complexes [Pt(mdt)2] (4; mdt = methyldithiolene, [Me2C2S2](n-)), [Pt(adt)2]
(5; adt = p-anisyldithiolene, [(MeO-p-C6H4)2C2S2](n-)), and [Pd(adt)2] (10) have
been prepared in yields of >=90% via transmetalation reactions with the
corresponding [R2Sn(S2C2R'2)] complexes (R = (n)Bu, R' = Me; R = Me, R' = -C6H4-p
OMe, 3). Intraligand C-S and C-Cchelate bond lengths (~1.71 and ~1.40 A,
respectively) obtained by X-ray crystallography show these compounds to be
comprised of radical monoanions mdt(*-) and adt(*-). The six-coordinate
octahedral adducts [Pt(adt)2(dppe)] [6; dppe = 1,2-bis(diphenylphosphino)ethane],
trans-[Pt(adt)2(PMe3)2] (8), and trans-[Pt(mdt)2(PMe3)2] (9) have also been
prepared, and crystal structures reveal dithiolene ligands that are fully reduced
ene-1,2-dithiolates (C-S and C-C(chelate) = ~1.77 and 1.35 A, respectively).
Reduction of the dithiolene ligand thus occurs to accommodate the +IV oxidation
state typical of octahedral six-coordinate platinum. The cyclic voltammogram of 5
shows two fully reversible reductions at -0.11 and -0.84 V in CH2Cl2 (vs
Ag/AgCl), attributed to successive (adt(*-) + e(-) -> adt(2-)) processes, and a
reversible oxidation at +1.01 V. The cyclic voltammogram of 9 shows two
reversible oxidations at +0.38 and +0.86 V, which are assigned as successive
(adt(2-) -> adt(*-) + e(-)) oxidations. Consistent with their formulation as
having fully reduced dithiolene ligands, the UV-vis spectra for 6, 8, and 9 show
no low-energy absorptions below 700 nm, and the S K-edge XAS spectra of 6 and 8
show dithiolene sulfur that is reduced relative to that in 5. The introduction of
PMe3 to 10 did not produce the palladium analogue of 8 but rather
[Pd(adt)(PMe3)2] (11). The reaction of [PdCl2(PPh3)2] with Li2(mdt) produced a
mixture of [Pd(mdt)(PPh3)2] (12, 20%) and [(Ph3P)Pd(MU-1,2-mdt-S,S':S)2Pd(PPh3)]
(13, 28%), with the latter having C2 symmetry with a Pd2S2 core structure folded
along the S...S axis.
PMID- 25113576
TI - Familias 3 - Extensions and new functionality.
AB - In relationship testing the aim is to determine the most probable pedigree
structure given genetic marker data for a set of persons. Disaster Victim
Identification (DVI) based on DNA data from presumed relatives of the missing
persons can be considered to be a collection of relationship problems. Forensic
calculations in investigative mode address questions like "How many markers and
reference persons are needed?" Such questions can be answered by simulations.
Mutations, deviations from Hardy-Weinberg Equilibrium (or more generally,
accounting for population substructure) and silent alleles cannot be ignored when
evaluating forensic evidence in case work. With the advent of new markers, so
called microvariants have become more common. Previous mutation models are no
longer appropriate and a new model is proposed. This paper describes methods
designed to deal with DVI problems and a new simulation model to study
distribution of likelihoods. There are softwares available, addressing similar
problems. However, for some problems including DVI, we are not aware of freely
available validated software. The Familias software has long been widely used by
forensic laboratories worldwide to compute likelihoods in relationship scenarios,
though previous versions have lacked desired functionality, such as the above
mentioned. The extensions as well as some other novel features have been
implemented in the new version, freely available at www.familias.no. The
implementation and validation are briefly mentioned leaving complete details to
Supplementary sections.
PMID- 25113577
TI - Choosing supplementary markers in forensic casework.
AB - The vast majority of human familial identifications based on DNA end up with a
well founded conclusion, normally using a standard set of genetic short tandem
repeat (STR) loci. There are, however, a proportion of cases that show ambiguous
results. For such occasions a number of different supplementary markers could be
typed in order to gain further information. There are numerous markers available
for such supplementary DNA typing, including STRs, deletion and insertion
polymorphisms (DIPs), and single nucleotide polymorphisms (SNPs). The purpose of
this work was to describe a precise method for decision making, aiming to aid the
comparison of different sets of markers for different case scenarios in order to
find the most efficient set for routine casework. Comparisons are based on a
particular function relating the expected additional value of information from
new data to the amount of information already obtained from initial data. The
function can be computed approximately by approximating likelihood-based error
rates using simulation. In this paper we focused on paternity investigations,
more specifically the use of supplementary markers in cases where a smaller
number of genetic inconsistencies make the matter inconclusive. We applied the
method to a comparison of three different kits: Investigator HDplex (STRs),
Investigator DIPplex (DIPs), and the SNPforID-plex (SNPs) to study their
efficiencies in gaining information in different case scenarios involving various
alternative relationships between the tested man and the tested child. We show
that the Investigator HDplex was the most efficient set of supplementary markers
for the standard paternity case. However, for paternity cases with a close
relative being the alternative father, the Investigator HDplex and the SNPforID
plex showed similar patterns in their ability to deliver a well-founded
conclusion. The Investigator DIPplex was the least efficient set.
PMID- 25113580
TI - Anterior segment optical coherence tomography in autosomal recessive cornea
plana.
PMID- 25113582
TI - Oxygenation by ruthenium monosubstituted polyoxotungstates in aqueous solution:
experimental and computational dissection of a Ru(III)-Ru(V) catalytic cycle.
AB - Molecular polyoxometalates with one embedded ruthenium center, with general
formula [Ru(II/III)(DMSO)XW11O39](n-) (X = P, Si; n = 4-6), are readily
synthesized in gram scale under microwave irradiation by a flash hydrothermal
protocol. These nanodimensional and polyanionic complexes enable aerobic
oxygenation in water. Catalytic oxygen transfer to dimethylsulfoxide (DMSO)
yielding the corresponding sulfone (DMSO2 ) has been investigated with a combined
kinetic, spectroscopic and computational approach addressing: (i ) the Ru(III)
catalyst resting state; (ii ) the bimolecular event dictating its transformation
in the rate-determining step; (iii ) its aerobic evolution to a high-valent
ruthenium oxene species; (iv ) the terminal fate to diamagnetic dimers. This
pathway is reminiscent of natural heme systems and of bioinspired artificial
porphyrins. The in silico characterization of a key bis-Ru(IV)-MU-peroxo-POM
dimeric intermediate has been accessed by density functional theory. This
observation indicates a new landmark for tracing POM-based manifolds for
multiredox oxygen reduction/activation, where metal-centered oxygenated species
play a pivotal role.
PMID- 25113581
TI - Fluoride inhibition of Sporosarcina pasteurii urease: structure and
thermodynamics.
AB - Urease is a nickel-dependent enzyme and a virulence factor for ureolytic
bacterial human pathogens, but it is also necessary to convert urea, the most
worldwide used fertilizer, into forms of nitrogen that can be taken up by crop
plants. A strategy to control the activity of urease for medical and agricultural
applications is to use enzyme inhibitors. Fluoride is a known urease inhibitor,
but the structural basis of its mode of inhibition is still undetermined. Here,
kinetic studies on the fluoride-induced inhibition of urease from Sporosarcina
pasteurii, a widespread and highly ureolytic soil bacterium, were performed using
isothermal titration calorimetry and revealed a mixed competitive and
uncompetitive mechanism. The pH dependence of the inhibition constants,
investigated in the 6.5-8.0 range, reveals a predominant uncompetitive mechanism
that increases by increasing the pH, and a lesser competitive inhibition that
increases by lowering the pH. Ten crystal structures of the enzyme were
independently determined using five crystals of the native form and five crystals
of the protein crystallized in the presence of fluoride. The analysis of these
structures revealed the presence of two fluoride anions coordinated to the Ni(II)
ions in the active site, in terminal and bridging positions. The present study
consistently supports an interaction of fluoride with the nickel centers in the
urease active site in which one fluoride competitively binds to the Ni(II) ion
proposed to coordinate urea in the initial step of the catalytic mechanism, while
another fluoride uncompetitively substitutes the Ni(II)-bridging hydroxide,
blocking its nucleophilic attack on urea.
PMID- 25113584
TI - Concise review: understanding clonal dynamics in homeostasis and injury through
multicolor lineage tracing.
AB - Lineage tracing is an essential tool to study stem cell fate. Although
traditional lineage tracing techniques have considerably advanced our
understanding of stem cell behavior, they pose significant limitations for
identification and longitudinal tracking of the progeny of individual stem cells,
to compare their behaviors. This is of importance given the well-established
heterogeneity among stem cells both in terms of potentialities and proliferative
capacities. The recent development of multicolor genetic reporters addressable to
specific cell populations largely overcomes these issues. These new "rainbow"
technologies provide increased resolution in clonal identification and offer the
possibility to study the relative distribution, contacts, tiled arrangement, and
competitive interactions among cells or groups of cells of the same type.
PMID- 25113583
TI - Effect of genetic and pharmacological blockade of GABA receptors on the 5-HT2C
receptor function during stress.
AB - Serotonin (5-HT)2C receptors play a role in psychoaffective disorders and often
contribute to the antidepressant and anxiolytic effects of psychotropic drugs.
During stress, activation of these receptors exerts a negative feedback on 5-HT
release, probably by increasing the activity of GABAergic interneurons. However,
to date, the GABA receptor types that mediate the 5-HT2C receptor-induced
feedback inhibition are still unknown. To address this question, we assessed the
inhibition of 5-HT turnover by a 5-HT2C receptor agonist (RO 60-0175) at the
hippocampal level and under conditions of stress, after pharmacological or
genetic inactivation of either GABA-A or GABA-B receptors in mice. Neither the
GABA-B receptor antagonist phaclofen nor the specific genetic ablation of either
GABA-B1a or GABA-B1b subunits altered the inhibitory effect of RO 60-0175,
although 5-HT turnover was markedly decreased in GABA-B1a knock-out mice in both
basal and stress conditions. In contrast, the 5-HT2C receptor-mediated inhibition
of 5-HT turnover was reduced by the GABA-A receptor antagonist bicuculline.
However, a significant effect of 5-HT2C receptor activation persisted in mutant
mice deficient in the alpha3 subunit of GABA-A receptors. It can be inferred that
non-alpha3 subunit-containing GABA-A receptors, but not GABA-B receptors, mediate
the 5-HT2C -induced inhibition of stress-induced increase in hippocampal 5-HT
turnover in mice.
PMID- 25113586
TI - Spatio-temporal variability of bovine tuberculosis eradication in Spain (2006
2011).
AB - In this study we analyzed the space-time variation of the risk of bovine
tuberculosis (bTB) in cattle between 2006 and 2011. The results indicated that at
country level, there were no significant temporal changes between years, but, at
county level bTB evolution was more heterogeneous. In some counties, between some
years, the prevalence and the incidence of the disease was higher as compared to
the global rate in the rest of the counties of Spain. The analysis of potential
risk factors indicated that both, a large number of movements from counties with
high incidence (>1%), and presence of bullfighting cattle herds increased bTB
risk. Red deer abundance, number of goats and number of mixed cattle-goat farms
were not significantly associated with the prevalence/incidence of bTB.
PMID- 25113587
TI - The choice of spatial scales and spatial smoothness priors for various spatial
patterns.
AB - Given the drawbacks for using geo-political areas in mapping outcomes unrelated
to geo-politics, a compromise is to aggregate and analyse data at the grid level.
This has the advantage of allowing spatial smoothing and modelling at a
biologically or physically relevant scale. This article addresses two consequent
issues: the choice of the spatial smoothness prior and the scale of the grid.
Firstly, we describe several spatial smoothness priors applicable for grid data
and discuss the contexts in which these priors can be employed based on different
aims. Two such aims are considered, i.e., to identify regions with clustering and
to model spatial dependence in the data. Secondly, the choice of the grid size is
shown to depend largely on the spatial patterns. We present a guide on the
selection of spatial scales and smoothness priors for various point patterns
based on the two aims for spatial smoothing.
PMID- 25113588
TI - GEOMED 2013--from spatial analysis to public health practice.
PMID- 25113585
TI - Low adherence to secondary prophylaxis among clients diagnosed with rheumatic
fever, Jamaica.
AB - OBJECTIVES: To determine the level of adherence and possible barriers to
secondary prophylaxis among clients with rheumatic fever in Kingston, Jamaica.
METHODS: Cross-sectional survey of 39 clients diagnosed with rheumatic fever,
receiving penicillin prophylaxis for more than a year using a 22-item self
administered questionnaire on adherence to secondary prophylaxis and knowledge of
rheumatic fever. The patients' records were reviewed to determine the number of
prophylaxis injections the patients received for the year 2010. RESULTS: The
majority of participants (74%) were females and 51% were adults. Only 48.7% had a
high level of adherence. The majority (72%) had low knowledge levels regarding
their illness, while only 5% had a high knowledge level score. Most clients (70%)
strongly agreed that nurses and doctors encouraged them to take their
prophylaxis. However, over 60% reported that they travelled long distances and or
waited long periods to get their injections. One-third reported that they missed
appointments because of fear of injections and having to take time off from work
or school. DISCUSSION: Clients attending the health centers studied had limited
knowledge about rheumatic fever. Barriers to adherence included fear of the
injections, long commutes, and long waiting periods at the facilities studied.
PMID- 25113589
TI - A spatio-temporal model for estimating the long-term effects of air pollution on
respiratory hospital admissions in Greater London.
AB - It has long been known that air pollution is harmful to human health, as many
epidemiological studies have been conducted into its effects. Collectively, these
studies have investigated both the acute and chronic effects of pollution, with
the latter typically based on individual level cohort designs that can be
expensive to implement. As a result of the increasing availability of small-area
statistics, ecological spatio-temporal study designs are also being used, with
which a key statistical problem is allowing for residual spatio-temporal
autocorrelation that remains after the covariate effects have been removed. We
present a new model for estimating the effects of air pollution on human health,
which allows for residual spatio-temporal autocorrelation, and a study into the
long-term effects of air pollution on human health in Greater London, England.
The individual and joint effects of different pollutants are explored, via the
use of single pollutant models and multiple pollutant indices.
PMID- 25113590
TI - Bayesian tracking of emerging epidemics using ensemble optimal statistical
interpolation.
AB - We present a preliminary test of the Ensemble Optimal Statistical Interpolation
(EnOSI) method for the statistical tracking of an emerging epidemic, with a
comparison to its popular relative for Bayesian data assimilation, the Ensemble
Kalman Filter (EnKF). The spatial data for this test was generated by a spatial
susceptible-infectious-removed (S-I-R) epidemic model of an airborne infectious
disease. Both tracking methods in this test employed Poisson rather than Gaussian
noise, so as to handle epidemic data more accurately. The EnOSI and EnKF tracking
methods worked well on the main body of the simulated spatial epidemic, but the
EnOSI was able to detect and track a distant secondary focus of infection that
the EnKF missed entirely.
PMID- 25113591
TI - Real geographies and virtual landscapes: exploring the influence on place and
space on mortality Lexis surfaces using shaded contour maps.
AB - This paper describes how shaded contour plots, applied to mortality data from the
Human Mortality Database, can be used to compare between nations, and start to
tease out some of the ways that place and space matters. A number of shaded
contour plots are presented, in order to describe the age, period and cohort
effects which are apparent within them. They show variations between different
subpopulations within the same nation, over time, and between nations. In
illustrating these intra- and international variations in the patterns, we hope
to encourage the development of hypotheses about the influence of such factors on
mortality rates. We conclude with a brief discussion about how such hypotheses
might be developed into statistical models, allowing for more rigourous testing
of hypotheses and projection across time, place and space.
PMID- 25113592
TI - Using geographical information systems and cartograms as a health service quality
improvement tool.
AB - INTRODUCTION: Disease prevalence can be spatially analysed to provide support for
service implementation and health care planning, these analyses often display
geographic variation. A key challenge is to communicate these results to decision
makers, with variable levels of Geographic Information Systems (GIS) knowledge,
in a way that represents the data and allows for comprehension. The present
research describes the combination of established GIS methods and software tools
to produce a novel technique of visualising disease admissions and to help
prevent misinterpretation of data and less optimal decision making. The aim of
this paper is to provide a tool that supports the ability of decision makers and
service teams within health care settings to develop services more efficiently
and better cater to the population; this tool has the advantage of information on
the position of populations, the size of populations and the severity of disease.
METHODS: A standard choropleth of the study region, London, is used to visualise
total emergency admission values for Chronic Obstructive Pulmonary Disease and
bronchiectasis using ESRI's ArcGIS software. Population estimates of the Lower
Super Output Areas (LSOAs) are then used with the ScapeToad cartogram software
tool, with the aim of visualising geography at uniform population density. An
interpolation surface, in this case ArcGIS' spline tool, allows the creation of a
smooth surface over the LSOA centroids for admission values on both standard and
cartogram geographies. The final product of this research is the novel Cartogram
Interpolation Surface (CartIS). RESULTS: The method provides a series of outputs
culminating in the CartIS, applying an interpolation surface to a uniform
population density. The cartogram effectively equalises the population density to
remove visual bias from areas with a smaller population, while maintaining
contiguous borders. CartIS decreases the number of extreme positive values not
present in the underlying data as can be found in interpolation surfaces.
DISCUSSION: This methodology provides a technique for combining simple GIS tools
to create a novel output, CartIS, in a health service context with the key aim of
improving visualisation communication techniques which highlight variation in
small scale geographies across large regions. CartIS more faithfully represents
the data than interpolation, and visually highlights areas of extreme value more
than cartograms, when either is used in isolation.
PMID- 25113593
TI - Assessment of land use factors associated with dengue cases in Malaysia using
Boosted Regression Trees.
AB - The transmission of dengue disease is influenced by complex interactions among
vector, host and virus. Land use such as water bodies or certain agricultural
practices have been identified as likely risk factors for dengue because of the
provision of suitable habitats for the vector. Many studies have focused on the
land use factors of dengue vector abundance in small areas but have not yet
studied the relationship between land use factors and dengue cases for large
regions. This study aims to clarify if land use factors other than human
settlements, e.g. different types of agricultural land use, water bodies and
forest are associated with reported dengue cases from 2008 to 2010 in the state
of Selangor, Malaysia. From the correlative relationship, we aim to generate a
prediction risk map. We used Boosted Regression Trees (BRT) to account for
nonlinearities and interactions between the factors with high predictive
accuracies. Our model with a cross-validated performance score (Area Under the
Receiver Operator Characteristic Curve, ROC AUC) of 0.81 showed that the most
important land use factors are human settlements (model importance of 39.2%),
followed by water bodies (16.1%), mixed horticulture (8.7%), open land (7.5%) and
neglected grassland (6.7%). A risk map after 100 model runs with a cross
validated ROC AUC mean of 0.81 (+/-0.001 s.d.) is presented. Our findings may be
an important asset for improving surveillance and control interventions for
dengue.
PMID- 25113595
TI - Terrestrial and freshwater Tardigrada of the Americas.
AB - This paper provides a comprehensive list of the freshwater and terrestrial
tardigrade fauna reported from the Americas (North America, South America,
Central America and the West Indies), their distribution in the Americas, and the
substrates from which they have been reported. Data were obtained from 316
published references. Authors' identifications were accepted at face value unless
subsequently amended. Taxa were assigned to sub-national units (states,
provinces, etc.). Many areas, in particular large portions of Central America and
the West Indies, have no reported tardigrade fauna. The presence of 54 genera and
380 species has been reported for the Americas; 245 species have been collected
in the Nearctic ecozone and 251 in the Neotropical ecozone. Among the tardigrade
species found in the Americas, 52 are currently considered cosmopolitan, while
153 species have known distributions restricted to the Americas. Based on recent
taxonomic revision of the genus Milnesium, the vast majority of records of M.
tardigradum in the Americas should now be reassigned to Milnesium tardigradum
sensu lato, either because the provided description differs from M. tardigradum
sensu stricto or because insufficient description is provided to make a
determination; the remainder should be considered Milnesium cf. tardigradum. Most
terrestrial tardigrade sampling in the Americas has focused on cryptogams
(mosses, lichens and liverworts); 90% of the species have been collected in such
substrates. The proportion of species collected in other habitats is lower: 14%
in leaf litter, 20% in soil, and 24% in aquatic samples (in other terrestrial
substrates the proportion never exceeds 5%). Most freshwater tardigrades have
been collected from aquatic vegetation and sediment. For nine species in the
Americas no substrates have been reported.
PMID- 25113594
TI - Assessing the impact of selective migration and care homes on geographical
inequalities in health--a total population cohort study in Sheffield.
AB - Selective migration and moves to care homes may potentially contribute to
observed socioeconomic gradients in mortality across cities and regions.
Sheffield has striking socioeconomic gradients in area-level mortality across the
city. We examined for evidence of selective migration and assessed the
contribution of migration to observed mortality gradients. We used a total
population cohort (539737 in 2001), linked mortality data (2001-2010) and linked
data from a health survey carried out in 2000 (66% response rate yielding 10185
responses). We used lower super-output areas and electoral wards as the spatial
units of analysis. We found clear evidence of selective migration. In the 25-44
age band, relative risks of mortality were 1.71 (95% CI 1.37-2.12) in migrants
from low to high deprivation areas compared with people remaining in low
deprivation areas, and 0.53 (0.42-0.65) in migrants from high to low deprivation
areas compared with people remaining in high deprivation areas. Relative risks
shrank towards unity with increasing age. Characteristics of migrants and non
migrants (illness prevalence, indicators of socioeconomic status, smoking
prevalence) ascertained before migration were largely consistent with the
relative risks for mortality and indicated that people carried their risks with
them. There was also a clear care homes effect, with higher mortality in
electoral wards with higher care home bed provision rates. Overall, however,
adjustment for selective migration, which included moves to care homes, made
little difference to gradients in inequality across the city. Our results suggest
that selective migration, including moves to care homes, do not explain existing
socioeconomic gradients in area level mortality across Sheffield.
PMID- 25113596
TI - A taxonomic review of the genus Megalostomis Chevrolat (Coleoptera,
Cryptocephalinae, Chrysomelidae).
AB - A taxonomic revision of the genus Megalostomis Chevrolat, 1836 (Coleoptera:
Chrysomelidae: Cryptocephalinae: Clytrini: Megalostomina) is provided, including
new data on geographic ranges. Two new species and 34 new synonymies are proposed
within the genus Megalostomis, leaving 42 valid species in the genus. A checklist
of the species of Megalostomis is provided, with information on host plants, ant
associations, and natural enemies. The study includes a key to all species,
diagnoses, descriptions, habitat, photographs, and distribution maps. This
comparative study of the external and internal adult morphology includes the male
and female genitalia. Nomenclatural acts proposed in this revision are as follow:
Change of status: M. dynamica stat. rev. (=M. flavipennis dynamica Monros, 1952).
New synonymy: M. anachoreta Lacordaire, 1848 (=M. gratiosa Lacordaire, 1848, syn.
nov., M. amazona Jacoby, 1876, syn. nov., M. generosa Baly, 1877a, syn. nov., M.
balyi Monros, 1951a, syn. nov., M. mariae Monros 1951a, new status syn., M.
hespenheidi Moldenke, 1981, syn. nov.); M. basilaris Jacoby, 1880 (= M. runa
Monros, 1952, syn. nov.); M. cornuta Lacordaire, 1848 (=M. cornuta var. divisa
Guerin, 1949, syn. nov.); M. dimidiata dimidiata (Lacordaire, 1848) (= M.
tomentosa tomentosa Jacoby, 1880, syn. nov., M. punctatissima (Jacoby, 1888),
syn. nov., M. tomentosa orientalis Moldenke, 1970, syn. nov., M. tomentosa
sinaloensis Moldenke, 1970, syn. nov., M. tomentosa guatemalensis Achard, 1926
(2nd specimen only), syn. nov., M. dimidiata nayaritensis Moldenke,
1970, syn. nov., M. dimidiata sonorensis Moldenke, 1970, syn. nov.); M.
flavocincta Lacordaire, 1848 (=M. flavomaculata Lacordaire, 1848, syn. nov.); M.
fulvipes fulvipes Jacoby, 1888 (=M. fulvipes yucatanensis Moldenke, 1970, syn.
nov.); M. gazella Lacordaire 1848 (=M. bicingulata, Lacordaire, 1848, syn. nov.,
M. meretrix Lacordaire, 1848, syn. nov.); M. luctuosa Lacordaire, 1848 (=M.
iracunda Lacordaire, 1848, syn. nov.); M. microcephala Lacordaire, 1848 [=M.
tosta (Monros, 1950), syn. nov.]; M. notabilis notabilis Lacordaire, 1848 (=M.
notabilis linearis Moldenke, 1970, syn. nov.); M. pyropiga pyropiga Lacordaire,
1848 (=M. pyropiga chiapensis Moldenke, 1970, syn. nov.); M. querula Lacordaire,
1848 (=M. propinqua Lacordaire, 1848, syn. nov., M. univittata pacifica Monros,
1953a, syn. nov.); M. religiosa Lacordaire, 1848 (=M. distincta Lacordaire, 1848,
syn. nov.); M. splendida splendida Lacordaire, 1848 (=M. splendida affinis
Jacoby, 1888, syn. nov.; M. splendida regalis Achard, 1926, syn. nov.); M.
subfasciata subfasciata (LeConte, 1868) [= M. subfasciata majorubrofasciata
Moldenke, 1970, syn. nov.; M. subfasciata murina (Monros, 1952), syn. nov.]; M.
tricincta (Germar, 1824) (=M. bubalus bubalus Lacordaire, 1848 syn. nov., M.
bubalus bubaloides Monros, 1953a, syn. nov.); M. univittata Lacordaire, 1848 (=M.
univittata oblita Monros, 1953a, syn. nov.); M. viridana Lacordaire, 1848 (=M.
metallica Jacoby, 1888, syn. nov.). Type designations: lectotypes are designated
for the following species: M. anachoreta Lacordaire, 1848; M. chalybeosoma
Lacordaire, 1848; M. coerulea Baly, 1877a; M. cornuta Lacordaire, 1848; M.
dimidiata Lacordaire, 1848; M. flavipennis Jacoby, 1880; M. flavocincta
Lacordaire, 1848; M. gazella Lacordaire, 1848; M. gigas Lacordaire, 1848; M.
interruptofasciata Baly, 1877a; M. luctuosa Lacordaire, 1848; M. notabilis
Lacordaire, 1848; M. obesa Lacordaire, 1848; M. placida Baly, 1877b; M. pyropiga
Lacordaire, 1848; M. religiosa Lacordaire, 1848; M. splendida Lacordaire, 1848;
M. subfasciata (LeConte, 1868); M. tricincta (Germar, 1824); M. unicincta
Lefevre, 1884; M. univittata Lacordaire, 1848; M. viridana Lacordaire, 1848; M.
microcephala Lacordaire, 1848.
PMID- 25113597
TI - Shared but overlooked: 30 species of Holarctic Microlepidoptera revealed by DNA
barcodes and morphology.
AB - This study reports 30 species of Lepidoptera previously known from either the
Palearctic or the Nearctic that are newly recorded as Holarctic. For 28 of these
species, their intercontinental distributions were initially detected through DNA
barcode analysis and subsequently confirmed by morphological examination; two
Palearctic species were first detected in North America through morphology and
then barcoded. When possible, the origin and status of each species (introduced,
overlooked Holarctic species, or unknowingly re-described) is discussed, and its
morphology is diagnosed and illustrated. The species involved include Tineidae:
Scardia amurensis Zagulajev, Triaxomera parasitella (Hubner), Nemapogon cloacella
(Haworth), Elatobia montelliella (Schantz), Tinea svenssoni Opheim;
Gracillariidae: Caloptilia suberinella (Tengstrom), Parornix betulae (Stainton);
Phyllonorycter maestingella (Muller); Yponomeutidae: Paraswammerdamia
albicapitella (Scharfenberg), P. conspersella (Tengstrom); Plutellidae: Plutella
hyperboreella Strand; Lyonetiidae: Lyonetia pulverulentella Zeller;
Autostichidae: Oegoconia deauratella (Herrich-Schaffer), O. novimundi (Busck);
Blastobasidae: Blastobasis glandulella (Riley), B. maroccanella (Amsel), B. tarda
Meyrick; Depressariidae: Agonopterix conterminella (Zeller), Depressaria
depressana (F.); Coleophoridae: Coleophora atriplicis Meyrick, C. glitzella
Hofmann, C. granulatella Zeller, C. texanella Chambers, C. vitisella Gregson;
Scythrididae: Scythris sinensis (Felder & Rogenhofer); Gelechiidae: Altenia
perspersella (Wocke), Gnorimoschema jalavai Povolny, Scrobipalpa acuminatella
(Sircom), Sophronia gelidella Nordman; Choreutidae: Anthophila fabriciana (L.);
and Tortricidae: Phiaris bipunctana (F.). These cases of previously unrecognized
faunal overlap have led to their redescription in several instances. Five new
synonyms are proposed: Blastobasis glandulella (Riley, 1871) = B. huemeri Sinev,
1993, syn. nov.; B. tarda Meyrick, 1902 = Neoblastobasis ligurica Nel & Varenne,
2004, syn. nov.; Coleophora atriplicis Meyrick, 1928 = C. cervinella McDunnough,
1946, syn. nov.; C. texanella Chambers, 1878 = C. coxi Baldizzone & van der Wolf,
2007, syn. nov., and = C. vagans Walsingham, 1907, syn. nov. Lectotypes are
designated for Blastobasis tarda Meyrick and Coleophora texanella Chambers. Type
specimens were examined where pertinent to establish new synonymies. We identify
12 previously overlooked cases of species introductions, highlighting the power
of DNA barcoding as a tool for biosurveillance.
PMID- 25113599
TI - Facile synthesis of 5-hydroxy-L-lysine from D-galactose as a chiral-precursor.
AB - A concise synthesis of (2S,5R) and (2S,5S)-5-hydroxy-lysine was achieved by
utilizing D-galactose as a chiral-precursor with stereo retention. This synthetic
strategy showcased the potential of utilizing carbohydrates as starting materials
to prepare amino acids. Using the diazido intermediate, the derived beta-D
galactopyranosyl and alpha-D-glucopyranosyl-(1->2)-beta-D-galactosyl moieties
were synthesized.
PMID- 25113598
TI - Fixed-target protein serial microcrystallography with an x-ray free electron
laser.
AB - We present results from experiments at the Linac Coherent Light Source (LCLS)
demonstrating that serial femtosecond crystallography (SFX) can be performed to
high resolution (~2.5 A) using protein microcrystals deposited on an ultra-thin
silicon nitride membrane and embedded in a preservation medium at room
temperature. Data can be acquired at a high acquisition rate using x-ray free
electron laser sources to overcome radiation damage, while sample consumption is
dramatically reduced compared to flowing jet methods. We achieved a peak data
acquisition rate of 10 Hz with a hit rate of ~38%, indicating that a complete
data set could be acquired in about one 12-hour LCLS shift using the setup
described here, or in even less time using hardware optimized for fixed target
SFX. This demonstration opens the door to ultra low sample consumption SFX using
the technique of diffraction-before-destruction on proteins that exist in only
small quantities and/or do not produce the copious quantities of microcrystals
required for flowing jet methods.
PMID- 25113600
TI - Endogenous peptide ligand-receptor systems for diverse signaling networks in
plants.
AB - Endogenous peptide ligand-receptor systems regulate cell-cell communications in
various developmental processes in plants. Recent studies have revealed that the
peptide-receptor combinations are not simply one-on-one with single roles. One
peptide activates multiple downstream signaling through different receptors,
while one receptor transmits different signals depending on peptide partners.
Peptide signaling pathways also crosstalk with signaling pathways of
phytohormones such as auxin, cytokinin and brassinosteroids. Furthermore,
environmental cues such as temperature, nutrient, and microbes activate or
inactivate peptide signaling pathways, which in turn modulate developmental
processes. This report summarizes recent advance on peptide-receptor signaling,
which makes a signaling network with phytohormone signaling pathways and
environmental responses.
PMID- 25113602
TI - Two coordination polymers constructed from a multidentate carboxylic acid ligand
with a tertiary amine serve as acid-base catalysts for the synthesis of
chloropropene carbonate from CO2 under atmospheric pressure.
AB - Two new coordination polymers, [Ni(H2O)(Hpdcd)(H2O)2].DMF (1) and
[Co(H2O)(Hpdcd)(H2O)2].DMF (2) (H3pdcd = 1-(4-carboxyphenyl)-2,5-dimethyl, 1H
pyrrole-3,4-dicarboxylic acid), which were designed based on a tertiary amine
ligand, were synthesized and characterized using multiple spectroscopy
techniques, including single-crystal X-ray diffraction. These two 1D linear
chains possess the properties of both a Lewis acid and organic base, which was
confirmed by temperature programmed desorption of ammonia and on-line mass
spectrometry (NH3-TPD-MS), and selective sorption for carbon dioxide. Due to
their acid-base properties, the compounds exhibited high catalytic activity, in
the absence of co-catalysts, for solvent-free synthesis of chloropropene
carbonate from CO2 and epichlorohydrin under atmospheric CO2 pressure. The yields
of chloropropene carbonate were 88% and 87% for 1 and 2, respectively, under the
optimized conditions.
PMID- 25113603
TI - An algorithm for score aggregation over causal biological networks based on
random walk sampling.
AB - BACKGROUND: We recently published in BMC Systems Biology an approach for
calculating the perturbation amplitudes of causal network models by integrating
gene differential expression data. This approach relies on the process of score
aggregation, which combines the perturbations at the level of the individual
network nodes into a global measure that quantifies the perturbation of the
network as a whole. Such "bottom-up" aggregation relates the changes in molecular
entities measured by omics technologies to systems-level phenotypes. However, the
aggregation method we used is limited to a specific class of causal network
models called "causally consistent", which is equivalent to the notion of balance
of a signed graph used in graph theory. As a consequence of this limitation, our
aggregation method cannot be used in the many relevant cases involving "causally
inconsistent" network models such as those containing negative feedbacks.
FINDINGS: In this note, we propose an algorithm called "sampling of spanning
trees" (SST) that extends our published aggregation method to causally
inconsistent network models by replacing the signed relationships between the
network nodes by an appropriate continuous measure. The SST algorithm is based on
spanning trees, which are a particular class of subgraphs used in graph theory,
and on a sampling procedure leveraging the properties of specific random walks on
the graph. This algorithm is applied to several cases of biological interest.
CONCLUSIONS: The SST algorithm provides a practical means of aggregating nodal
values over causally inconsistent network models based on solid mathematical
foundations. We showed its utility in systems biology, where the nodal values can
be perturbation amplitudes of protein activities or gene differential
expressions, while the networks can be models of cellular signaling or expression
regulation. Since the SST algorithm is based on general graph-theoretical
considerations, it is scalable to arbitrary graph sizes and can potentially be
used for performing quantitative analyses in any context involving signed graphs.
PMID- 25113604
TI - PI3K, MAPK EPK1/2 and p38 are involved in the realization of growth potential of
mesenchymal progenitor cells under the influence of basic fibroblast growth
factor.
AB - We studied PI3K, MAPK/EPK1/2 and p38-dependent signaling cascade under
stimulation of the functions of mesenchymal progenitor cells by fibroblast growth
factor. The important role of PI3K and EPK1/2 in the realization of their growth
potential has been revealed. Experiments have demonstrated a blocking effect of
PI3K inhibitor on proliferation and differentiation of progenitor cells and
EPK1/2 inhibitor on mitotic activity of the progenitor cells. The p38-mediated
MAPK pathway did not play a role in determining the proliferative and
differentiation status of fibroblast CFU.
PMID- 25113601
TI - 17beta-estradiol differentially regulates stress circuitry activity in healthy
and depressed women.
AB - Many regions within stress neurocircuitry, including the anterior hypothalamus,
amygdala, hippocampus, and medial prefrontal cortex, are densely populated with
sex steroid receptors. Substantial evidence from animal studies indicates that
the gonadal hormone 17beta-estradiol (E2) impacts the structure and function of
these regions, but human studies are limited. Characterizing estradiol's role in
stress circuitry in vivo in humans may have important clinical implications given
the comorbidity between major depressive disorder (MDD), stress circuitry
dysfunction and endocrine dysregulation. In this study, we determined estradiol's
role in modulating activity within cortical and subcortical stress circuitry
regions in healthy and MDD women. Subjects were part of a population-based birth
cohort, the New England Family Study. Capitalizing on the endogenous fluctuation
in E2 during the menstrual cycle, we conducted a within-person repeated-measures
functional neuroimaging study in which 15 women with recurrent MDD, in remission,
and 15 healthy control women underwent hormonal evaluations, behavioral testing,
and fMRI scanning on two occasions, under low and high E2 conditions. Subjects
completed an fMRI scan while undergoing a mild visual stress challenge that
reliably activated stress neural circuitry. Results demonstrate that E2 modulates
activity across key stress circuitry regions, including bilateral amygdala,
hippocampus, and hypothalamus. In healthy women, robust task-evoked BOLD signal
changes observed under low E2 conditions were attenuated under high E2
conditions. This hormonal capacity to regulate activity in stress circuitry was
not observed in MDD women, despite their remitted status, suggesting that
dysregulation of gonadal hormone function may be a characteristic trait of the
disease. These findings serve to deepen our understanding of estradiol's actions
in the healthy brain and the neurobiological mechanisms that may underlie the
pronounced sex difference in MDD risk.
PMID- 25113605
TI - Functional and metabolic changes in the brain in neuropathic pain syndrome
against the background of chronic epidural electrostimulation of the spinal cord.
AB - Changes in functional and metabolic activities of the brain were evaluated by EEG
and positron-emission/computer tomography with 18F-fluorodeoxyglucose in patients
with neuropathic pain syndrome previous to and 3 months after implantation of a
system for chronic epidural spinal cord stimulation. In most cases, the use of a
nerve stimulator was followed by alleviation of neuropathic pain and partial
normalization of functional and metabolic activities of brain structures
responsible for pain perception, emotiogenic, behavioral, and autonomic
responses.
PMID- 25113607
TI - Relationship between brain natriuretic peptides and recurrence of atrial
fibrillation after successful direct current cardioversion: a meta-analysis.
AB - BACKGROUND: Atrial fibrillation (AF) recurrence is common after successful direct
current cardioversion (DCCV), with a 40% rate of recurrence within the first
month. Several studies have investigated the potential association between brain
natriuretic peptide (BNP) or N-terminal (NT)-proBNP levels before DCCV and the
risk of AF recurrence, but results have been inconsistent. We, therefore,
conducted a systematic review and meta-analysis of all available data to
determine whether sinus rhythm (SR) maintenance after successful DCCV may be
determined by preprocedural BNP and NT-proBNP levels. METHODS: We systematically
searched Scopus, the Cochrane library, EMBASE, and MEDLINE databases to identify
publications evaluating BNP or NT-proBNP levels in relation to post-DCCV AF
recurrence, indexed from inception to September 2013. Among the initial 1,067
citations, 18 studies fulfilled the specified criteria. The difference in BNP and
NT-proBNP concentrations in the AF recurrence and the SR-maintaining group was
estimated by the standardized mean difference and the estimates of the pooled
outcomes were evaluated using random-effects models. RESULTS: Baseline BNP levels
in the AF recurrence group were significantly higher compared to BNP levels in
the SR-maintaining group (standardized mean difference [SMD] -1.51, confidence
interval [CI] [-2.53, -0.48], P = 0.004). Similar results were observed for NT
proBNP levels, which were significantly higher in the AF recurrence group
compared with the SR-maintaining group (SMD -0.63, CI [-1.13, -0.14], P = 0.01).
CONCLUSIONS: Our analysis suggests that low preprocedural BNP/NT-proBNP levels
are associated with SR maintenance. The use of BNP or NT-proBNP for prediction of
long-term response to DCCV appears to be useful and should be further evaluated.
PMID- 25113608
TI - Developmental profiles of GFAP-positive astrocytes in sheep cerebellum.
AB - Astroglial account for the largest glial population in the brain and play a
variety of vital functions in the development of the central nervous system
(CNS). An immunohistochemical study was performed in 19 ovine foetuses ranging
from 2 to 5 months of gestation, one newborn lamb and three adult sheep. Using
the anit-glial fibrillary acidic protein (GFAP) marker, several variations were
found in the degree of GFAP positive (GFAP+) astrocyte distribution between the
different zones in the cerebellum of sheep during brain development. Our study
indicates that the first appearance of astrocytes from restricted zones in the
cerebellum occurs around the eighth week of gestation. Bergmann cells were found
to be present from around the 15th week of gestation onwards. Our findings
suggest that the maturation of astrocytes begins in the caudal parts of the
cerebellum, developing from their initial ventral regions to spread first to
dorsal regions radially within the white matter, then followed by the more
rostral parts of the cerebellum. Astrocytes were also found to proliferate in the
vermis before appearing in the cerebellar hemispheres.
PMID- 25113610
TI - Systematic review and meta-analysis on the efficacy of selective laser
trabeculoplasty in open-angle glaucoma.
AB - Selective laser trabeculoplasty (SLT) is a relatively new type of laser used in
treating open-angle glaucoma (OAG) and is reported to be equally efficacious to a
first-line medication and argon laser trabeculoplasty (ALT). We summarize
available evidence for considering SLT as an alternative treatment in OAG through
systematic review and meta-analysis. Among OAG patients who range from newly
diagnosed to those on maximally tolerated medical therapy, SLT results in a 6.9
35.9% intraocular pressure (IOP) reduction. Complications are rare and include an
IOP spike requiring surgery, persistent macular edema, and corneal haze and
thinning. Meta-analysis of randomized, controlled trials shows that SLT is non
inferior to ALT and medication in IOP reduction and also in achieving treatment
success. Number of medications reduction is similar between SLT and ALT. More
robust evidence is needed to determine its efficacy as a repeated procedure.
PMID- 25113606
TI - Spatial patterns of neuronal activity in rat cerebral cortex during non-rapid eye
movement sleep.
AB - It is commonly assumed that cortical activity in non-rapid eye movement sleep
(NREMS) is spatially homogeneous on the mesoscopic scale. This is partly due to
the limited observational scope of common metabolic or imaging methods in sleep.
We used the recently developed technique of thallium-autometallography (TlAMG) to
visualize mesoscopic patterns of activity in the sleeping cortex with single-cell
resolution. We intravenously injected rats with the lipophilic chelate complex
thallium diethyldithiocarbamate (TlDDC) during spontaneously occurring periods of
NREMS and mapped the patterns of neuronal uptake of the potassium (K+) probe
thallium (Tl+). Using this method, we show that cortical activity patterns are
not spatially homogeneous during discrete 5-min episodes of NREMS in unrestrained
rats-rather, they are complex and spatially diverse. Along with a relative
predominance of infragranular layer activation, we find pronounced differences in
metabolic activity of neighboring neuronal assemblies, an observation which lends
support to the emerging paradigm that sleep is a distributed process with
regulation on the local scale.
PMID- 25113609
TI - Palinopsia revamped: a systematic review of the literature.
AB - Palinopsia, the persistence or recurrence of visual images after the stimulus has
been removed, is a nonspecific term that describes multiple types of visual
symptoms with a wide variety of etiologies. For example, palinopsia may be the
presenting symptom of a potentially life-threatening posterior cortical lesion,
yet it may also be a benign medication side effect. We comprehensively review all
published cases and subdivide palinopsia into two clinically relevant categories:
illusory palinopsia and hallucinatory palinopsia.
PMID- 25113611
TI - Systematic review of 342 cases of endogenous bacterial endophthalmitis.
AB - We review a total of 342 cases of endogenous bacterial endophthalmitis reported
between 1986 and 2012. Predisposing conditions were present in 60%, most commonly
diabetes, intravenous drug use, and malignancy. The most common sources of
infection were liver, lung, endocardium, urinary tract, and meninges. Systemic
features such as fever were present in 74%, hypopyon in 35%, and an absent fundal
view in 40%. Diagnostic delay occurred in 26%. Blood cultures were positive in
56%, and at least one intraocular sample was positive in 58% (comprising 26%
anterior chamber samples, 59% vitreous taps, and 41% vitrectomy specimens).
Worldwide, Gram negative infections (55%) were more frequent than Gram positive
(45%) infections, particularly in Asia. Over the last decade, 11% of eyes were
treated with systemic antibiotics alone, 10% intravitreal antibiotics alone, 36%
systemic plus intravitreal antibiotics, and 20% systemic plus intravitreal
antibiotics plus pars plana vitrectomy. The most commonly used intravitreal
antibiotics were vancomycin (for Gram positive infection) and ceftazidime (Gram
negative). The median final visual acuity was 20/100, with 44% worse than 20/200.
Among all cases, 24% required evisceration or enucleation, and mortality was 4%.
Both intravitreal dexamethasone and vitrectomy were each associated with a
significantly greater chance of retaining 20/200 or better and significantly
fewer eviscerations or enucleations-these warrant further study. For most
patients, treatment should include a thorough systemic evaluation and prompt
intravitreal and systemic antibiotics.
PMID- 25113612
TI - Acoustic reflectors are visible in the right heart during radiofrequency ablation
of varicose veins.
AB - OBJECTIVE: Cerebrovascular events have been noted after foam sclerotherapy for
varicose veins. One hypothesis is migration of microemboli to the brain through a
cardiac septal defect. The aim of this study was to identify whether acoustic
reflectors are found in the right side of the heart during radiofrequency
ablation of varicose veins, as neurological events are not reported during these
procedures. METHODS: Transthoracic echocardiography was performed during local
anaesthetic radiofrequency ablation (VNUS ClosureFast) of the great saphenous
vein in 14 patients. An apical view was captured at the start of the procedure,
during each cycle of heating and at 1 min post-treatment. Patients were monitored
for 1 h. Video loops were read by an independent cardiologist. The presence of
acoustic reflectors was classified as: 0 = absent, 1 = occasional, 2 = stream, 3
= complete opacification. RESULTS: Loops were of diagnostic quality in 11/14
(79%) patients. After the second cycle of heating, acoustic reflectors moving
through the right heart were seen in 5/11 (45%) patients. These were classified
as grade 1 in four patients and grade 2 in one patient. No acoustic reflectors
were seen in the left heart. No neurological symptoms were reported. CONCLUSION:
Acoustic reflectors in the right heart are a common finding during radiofrequency
ablation of varicose veins. Considering the prevalence of cardiac septal defects
(17%), more neurological events would be expected if these particles were indeed
responsible for these events. Further work is required to elicit the mechanisms
underlying neurological complications following sclerotherapy.
PMID- 25113613
TI - Synthesis and role of salicylic acid in wheat varieties with different levels of
cadmium tolerance.
AB - Wheat genotypes with different endogenous SA contents were investigated, in order
to reveal how cadmium influences salicylic acid (SA) synthesis, and to find
possible relationships between SA and certain protective compounds (members of
the antioxidants and the heavy metal detoxification system) and between the SA
content and the level of cadmium tolerance. Cadmium exposure induced SA
synthesis, especially in the leaves, and it is suggested that the phenyl
propanoid synthesis pathway is responsible for the accumulation of SA observed
after cadmium stress. Cadmium influenced the synthesis and activation of
protective compounds to varying extents in wheat genotypes with different levels
of tolerance; the roots and leaves also responded differently to cadmium stress.
Although a direct relationship was not found between the initial SA levels and
the degree of cadmium tolerance, the results suggest that the increase in the
root SA level during cadmium stress in the Mv varieties could be related with the
enhancement of the internal glutathione cycle, thus inducing the antioxidant and
metal detoxification systems, which promote Cd stress tolerance in wheat
seedlings. The positive correlation between certain SA-related compounds and
protective compounds suggests that SA-related signalling may also play a role in
the acclimation to heavy metal stress.
PMID- 25113615
TI - Static headspace-multicapillary column with gas chromatography coupled to ion
mobility spectrometry as a simple approach for the discrimination of crude and
processed traditional Chinese medicines.
AB - The processing procedure can alter the nature and chemical transformation of
traditional Chinese medicine to accommodate different clinical dispensing and
preparation requirements. In this study, static headspace-multicapillary column
with gas chromatography coupled to ion mobility spectrometry was developed for
the rapid and sensitive discrimination of crude and processed traditional Chinese
medicine. Using Radix Paeoniae Alba as a traditional Chinese medicine model, the
combined power of this approach was illustrated by classifying the crude and
processed Radix Paeoniae Alba samples into two main categories. The contents of
the main components in Radix Paeoniae Alba varied significantly. The established
method could promote the use of ion mobility spectrometry in intrinsic quality
control and differentiation of herbal medicines from other processed products or
preparations.
PMID- 25113614
TI - Effect of paddy-upland rotation on methanogenic archaeal community structure in
paddy field soil.
AB - Methanogenic archaea are strict anaerobes and demand highly reduced conditions to
produce methane in paddy field soil. However, methanogenic archaea survive well
under upland and aerated conditions in paddy fields and exhibit stable community.
In the present study, methanogenic archaeal community was investigated in fields
where paddy rice (Oryza sativa L.) under flooded conditions was rotated with
soybean (Glycine max [L.] Merr.) under upland conditions at different rotation
histories, by polymerase chain reaction (PCR)-denaturing gradient gel
electrophoresis (DGGE) and real-time quantitative PCR methods targeting 16S rRNA
and mcrA genes, respectively. Soil samples collected from the fields before
flooding or seeding, during crop cultivation and after harvest of crops were
analyzed. The abundance of the methanogenic archaeal populations decreased to
about one-tenth in the rotational plots than in the consecutive paddy (control)
plots. The composition of the methanogenic archaeal community also changed. Most
members of the methanogenic archaea consisting of the orders Methanosarcinales,
Methanocellales, Methanomicrobiales, and Methanobacteriales existed
autochthonously in both the control and rotational plots, while some were
strongly affected in the rotational plots, with fatal effect to some members
belonging to the Methanosarcinales. This study revealed that the upland
conversion for one or longer than 1 year in the rotational system affected the
methanogenic archaeal community structure and was fatal to some members of
methanogenic archaea in paddy field soil.
PMID- 25113616
TI - Anthropometric and craniofacial sexual dimorphism in obstructive sleep apnea
patients: is there male-female phenotypical convergence?
AB - Obstructive sleep apnea (OSA) is more common in men than women. Body size is
greater in males (sexual dimorphism), but large body habitus is associated with
OSA for both genders. We speculated that male-female phenotypical convergence
(reduced sexual dimorphism via identical phenotype acquisition) occurs with OSA
and tested hypotheses: (1) phenotypical features pathogenic for OSA differ
between OSA and healthy subjects irrespective of gender; and (2) such
characteristics exhibit phenotypical convergence. Utilizing an existing database,
we calculated male-female (group average) ratios for eight anthropometric and 33
surface cephalometric variables from 104 Caucasian OSA patients [72 males; apnea
hypopnea index (events h(-1) ): males: 42.3 +/- 24.7 versus females: 42.6 +/-
26.1 (P > 0.9)] and 85 Caucasian, healthy, non-OSA, community volunteers (36
males). Log-transformed data were analysed using a general linear model with post
hoc unpaired t-tests and significance at P < 0.0012 (Bonferroni multiple
comparison correction). OSA patients were older (56.9 +/- 14.4 versus 38.0 +/-
13.8 years), but there were no within-group gender-based age differences. All
anthropometric variables (except height), plus cranial base width, mandibular
breadth and retromandibular width diagonal were larger in gender-matched OSA
versus healthy comparisons; thus satisfying hypothesis (1). Male-female ratios
were mostly >1.0 across groups, but with no significant group * gender
interactions no variable satisfied hypothesis (2). Thus, in this exploratory
study, OSA patients had gender-common phenotypical differences to healthy
subjects, but sexual dimorphism was preserved. Lack of complete phenotypical
convergence may indicate gender-based critical phenotype-level attainment for OSA
and/or gender-based OSA prevalence arises from factors other than those in this
study.
PMID- 25113617
TI - N-alkylacylamides in thin films display infrared spectra of 310-, alpha-, and pi
helices with visible static and dynamic growth phases.
AB - A peptide model is a physical system containing a CONH group, the simplest being
HCONHCH3 , N-methylformamide (NMF). We have discovered that NMF and N
methylacetamide (NMA), which form hydrogen-bonded oligomers in thin films on a
planar AgX fiber, display infrared (IR) spectra with peaks like those of
polypeptide helices. Structures can be assigned by their amide I maxima near 1672
(3(10)), 1655 (3(10)), 1653 (alpha), 1655 (pi), and 1635 cm(-1) (pi), which are
the first IR data for the pi-helix. Sharp peaks are an outcome of immobilization
of polar species on the polar surface of silver halides. We report the first use
of expanded thin-film IR spectroscopy, in which plots of every spectrum over the
amide I-II range show pauses or slow stages in the increase or decrease of
absorption. These are identified as static phases followed by dynamic phases,
with the incremental gain or loss of a helix turn. A general theory can be stated
for such processes. Density functional calculations show that the NMA alpha-helix
pentamer (crystal structure geometry) is transformed into a pi-helix-like form.
For the first time, an entire sequence (3(10)-helix, alpha-helix, pi-helix,
quasiplanar species) of spectra has been recorded for NMA.
PMID- 25113618
TI - The gene expression profile of cumulus cells reveals altered pathways in patients
with endometriosis.
AB - PURPOSE: The objective of this experimental study was to compare the global gene
expression profile of CC of mature oocytes in 18 patients with severe
endometriosis and CC in 18 control patients affected by a severe male factor.
METHODS: For each group, the CC were pooled, RNA was extracted and a microarray
performed. For validating the microarray, a quantitative real-time PCR was
performed in the CC of an independent set of patients with endometriosis (n = 5)
and controls (n = 7). RESULTS: 595 differentially expressed genes (320 down
regulated, 275 up-regulated, p < 0.05, fold change >=1.5) were identified. The
most significant changes were observed in genes involved in the chemokine
signaling and cell-cell or cell-extracellular matrix adhesion pathways. Several
genes of these pathways were down-regulated in endometriosis. Individual RT-PCR
assays confirmed the microarray for ten genes. CONCLUSIONS: Several genes
involved in the chemokine mediated-signaling pathway and in the functional cross
talk between CC and the oocyte are down-regulated in endometriosis CC. The
impairment of these processes could explain the reduction of oocyte competence in
endometriosis. This preliminary knowledge could be the starting point for a more
detailed elucidation of the relationship between endometriosis and oocyte
competence.
PMID- 25113619
TI - Protein modification as oxidative stress marker in follicular fluid from women
with polycystic ovary syndrome: the effect of inositol and metformin.
AB - PURPOSE: The purpose of this study was to evaluate the oxidative stress status
(OS) of follicular fluid (FF) and the oocyte quality in women with polycystic
ovary syndrome (PCOS) undergoing different ovarian stimulation protocols.
METHODS: FF samples were collected after gonadotropin administration in
association or not with metformin or D-chiro-inositol (DCI). OS status was then
evaluated by checking the follicular fluid protein oxidation profile after
specific labeling of aminoacidic free-SH groups, and two-dimensional
electrophoresis followed by qualitative and semiquantitative analysis. Oocyte
quality was assessed by international morphological criteria. RESULTS: Our data
indicated that both treatments, even if to different extent, recovered a
significantly high level of free-SH groups in FF proteins of PCOS women clearly
indicating a decrease of OS level with respect to that found in FF samples from
gonadotropins alone treated women. A higher number of good quality MII oocytes
was also observed in DCI (P < 0.05) or metformin (P < 0.05) study groups in
comparison to untreated control group. CONCLUSION: A natural supplement and a
drug both showed a statistically significant positive effect on follicular milieu
by decreasing the oxidative damage on FF proteins, as well as in recovering good
quality oocytes.
PMID- 25113621
TI - Clinical pregnancy in a woman with idiopathic hypogonadotropic hypogonadism and
low AMH: utility of ovarian reserve markers in IHH.
AB - OBJECTIVE: Serum anti-mullerian hormone (AMH) has been proposed as a useful
marker of ovarian reserve that is cycle-independent and predictive of outcome in
assisted reproduction cycles. However, there is evidence that AMH production is
gonadotropin-dependent, and that under the influence of FSH, growing follicles
contribute to circulating AMH levels. Therefore, AMH testing may not be
universally reflective of the primordial follicle pool in certain conditions. We
demonstrate that in patients with idiopathic hypogonadotropic hypogonadism (IHH)
and deficient gonadotropin production, AMH and antral follicle count (AFC) may
not be reliable markers of ovarian reserve. DESIGN: Case report. SETTING:
Fertility clinic at a tertiary academic hospital. PATIENT: A 30-year-old
nulligravid patient with IHH who presented for fertility treatment with low FSH
(0.3 IU/L), LH (0.1 IU/L), estradiol (77 pmol/L) and AMH levels (0.65 pmol/L),
and an unmeasurable AFC. INTERVENTION: A three-month course of priming with oral
micronized 17beta-estradiol, followed by daily injections of human menopausal
gonadotropins (hMG). MAIN OUTCOME MEASURE: AMH level and follicular development.
RESULTS: After 60 days of stimulation with hMG, the patient's AMH level increased
to a peak of 1.27 pmol/L. After 102 days of stimulation, her estradiol level rose
to 480 pmol/L and a 19 mm dominant follicle was detected. The patient
successfully conceived with intrauterine insemination. CONCLUSION: Ovarian
reserve testing in patients with IHH can be challenging due to the contracted
appearance of the ovaries and deficient FSH production. In these patients, AMH
levels may underestimate ovarian reserve due to the lack of FSH-dependent growing
follicles. When treated with a long course of hMG, these patients may exhibit
increased AMH levels and demonstrate adequate follicular development.
PMID- 25113622
TI - Controlling adverse and beneficial effects of solar UV radiation by wearing
suitable clothes - spectral transmission of different kinds of fabrics.
AB - Humans should avoid prolonged exposure to the Sun during the warm subperiod of
the year with naturally high solar UV level. One of the known recommendations to
avoid excessive UV radiation is wearing clothes with UV protection additives.
However there is an important question: how do we get an adequate solar UV
radiation, which maintains a healthy status of vitamin D, without facing
overexposure risks? It is found that some kind of 100% cotton knitted fabric,
used in the production of normal daily clothing, has ~15% transmittance of solar
UV. Model studies show that a garment made of this fabric allows larger synthesis
of vitamin D3 in human body without the erythema risks (skin redness). Thus the
adequate level of vitamin D could be attained safely by a person exposing only
small part of the body (face, palms) during the period (May-August) of the year.
PMID- 25113620
TI - Effects of group culture on the development of discarded human embryos and the
construction of human embryonic stem cell lines.
AB - PURPOSE: To explore the effect of group culture on the developmental potential of
discarded embryos in in vitro fertilization/intracytoplasmic sperm injection
(IVF/ICSI) cycles and establish the human embryonic stem cell lines for future
research. METHORDS: Fresh discarded embryos were collected from the IVF/ICSI-ET
program in the reproductive medical center of the first affiliated hospital of
Zhengzhou university in this study. All zygotes were individually cultured from
Day 1 to Day 3. On Day 3, discard embryos were then cultured in group of 1-4
embryos per droplet (30 MUl/droplets) with a constant culture medium until Day 5
or 6. Mechanical method was used to isolate the inner cell mass (ICM) of
blastocyst from the embryo. Then we inoculated the ICM on feeder layer. After
identification of those cells, the human embryonic stem cell lines (hESCs) were
established. RESULTS: In this study, we collected 1,223 fresh discarded embryos
and they were sequential cultured to the blastocysts (18.07 %, 221/1,223), in
which good quality blastocysts were 61(4.98 %, 61/1,223). There was no
significant difference in the patients. The embryos from 1PN, 2PN, 3PN were
sequential cultured to the blastocyst s(39.31 %,92/234;12.87 %,64/497;13.21
%,65/492),in which good quality blastocysts was 13.6 %(32/92),2.61 %(13/64), 3.04
%(15/65).1PN embryo's blastulation rate and quality embryo formation rate was
significantly higher than the 2PN and 3PN embryos' (P <0.05). Three embryos group
cultivation has the highest blastulation rate and quality embryo formation rate
(P <0.05). In total, we successfully established 4 hESCs lines. CONCLUSION: The
group culture of human discard embryos can improve the blastulation rate and
blastocyst quality to some extent. Three embryos group cultivate is the better
culture number. Human discard embryos are good source for establishment of hESCs.
PMID- 25113623
TI - Extramammary Paget's disease of the perianal region: a 20-year experience.
AB - BACKGROUND: To evaluate the results obtained from cases of perianal Paget's
disease (PPD) and to provide a current perspective in the diagnostic evaluation
and surgical management of this condition. METHODS: A retrospective review of a
single quaternary referral centre's experience with PPD from January 1994 to
December 2013 was performed. Medical records were reviewed to collect data on
demographics, preoperative investigations, complications, pathology and
recurrence. A review of existing literature was also performed. RESULTS: Five
patients (four females, one male) with histologically confirmed PPD were
identified. The median age of presentation was 72 (range 61 to 78). Three
patients were recurrences following previous excisions and first presentations in
two patients. Only one patient had an underlying diagnosis of cancer. The median
time to diagnosis was 24 months. Four patients underwent wide local excision with
skin graft and/or local flap reconstruction and one patient required an
abdominoperineal excision for recurrence. Four patients had involved lateral
margins despite wide local excision but follow-up to date has only revealed one
local recurrence. A review of available literature suggests that synchronous
cancers can occur in up to 33% of patients and that a further 10% may be
associated with metachronous cancers. Surveillance recommendations seem anecdotal
and do not appear to be supported by available literature. CONCLUSION: PPD is a
management challenge. Association with synchronous and metachronous carcinomas
may not be as strong as initially thought. Surgery is the mainstay treatment with
the need to balance between minimizing disease recurrence and functional sequelae
from excessive tissue loss.
PMID- 25113624
TI - A systematic review of the effectiveness of individual, community and societal
level interventions at reducing socioeconomic inequalities in obesity amongst
children.
AB - BACKGROUND: Tackling childhood obesity is one of the major contemporary public
health policy challenges and vital in terms of addressing socioeconomic health
inequalities.We aimed to systematically review studies of the effectiveness of
interventions (individual, community and societal) operating via different
approaches (targeted or universal) in reducing socio-economic inequalities in
obesity-related outcomes amongst children. METHODS: Nine electronic databases
were searched from start date to October 2012 along with website and grey
literature searches. The review examined the best available international
evidence from interventions that aimed to prevent obesity, treat obesity, or
improve obesity-related behaviours (diet and/or physical activity) amongst
children (aged 0-18 years) in any setting and country, so long as they provided
relevant information and analysis on both socioeconomic status and obesity
related outcomes. Data extraction and quality appraisal were conducted using
established mechanisms and narrative synthesis was conducted. RESULTS: We located
23 studies that provided the 'best available' (strongest methodologically)
international evidence. At the individual level (n = 4), there was indicative
evidence that screen time reduction and mentoring health promotion interventions
could be effective in reducing inequalities in obesity. For the community level
interventions (n = 17), evidence was inconclusive - with some studies suggesting
that school-based health promotion activities and community-based group-based
programmes were effective in reducing obesity - others not. Societal level
evaluations were few (n = 1). However, there was no evidence to suggest that any
of these intervention types increase inequalities and several studies found that
interventions could at least prevent the widening of inequalities in obesity. The
majority of studies were from America and were of 6-12 year old children.
CONCLUSIONS: The review has found only limited evidence although some individual
and community based interventions may be effective in reducing socio-economic
inequalities in obesity-related outcomes amongst children but further research is
required, particularly of more complex, societal level interventions and amongst
adolescents.
PMID- 25113625
TI - A semi-probabilistic modelling approach for the estimation of dietary exposure to
phthalates in the Belgian adult population.
AB - In this study, a semi-probabilistic modelling approach was applied for the
estimation of the long-term human dietary exposure to phthalates--one of world's
most used families of plasticisers. Four phthalate compounds were considered:
diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), benzylbutyl phthalate (BBP)
and di(2-ethylhexyl) phthalate (DEHP). Intake estimates were calculated for the
Belgian adult population and several subgroups of this population for two
considered scenarios using an extended version of the EN-forc model. The highest
intake rates were found for DEHP, followed by DnBP, BBP and DEP. In the Belgian
adult population, men and young adults generally had the highest dietary
phthalate intake estimates. Nevertheless, predicted dietary intake rates for all
four investigated phthalates were far below the corresponding tolerable daily
intake (TDI) values (i.e. P99 intake values were 6.4% of the TDI at most), which
is reassuring because adults are also exposed to phthalates via other
contamination pathways (e.g. dust ingestion and inhalation). The food groups
contributing most to the dietary exposure were grains and grain-based products
for DEP, milk and dairy products for DnBP, meat and meat products or grains and
grain-based products (depending on the scenario) for BBP and meat and meat
products for DEHP. Comparison of the predicted intake results based on modelled
phthalate concentrations in food products with intake estimates from other
surveys (mostly based on measured concentrations) showed that the extended
version of the EN-forc model is a suitable semi-probabilistic tool for the
estimation and evaluation of the long-term dietary intake of phthalates in
humans.
PMID- 25113626
TI - Effect modification of ozone-related mortality risks by temperature in 97 US
cities.
AB - Many time-series studies have characterized the relationship between short-term
ozone exposure and adverse health outcomes, controlling for temperature as a
confounder. Temperature may also modify ozone effects, though this has been
largely under-investigated. In this study, we explored whether temperature
modifies the effect of short-term ozone exposure on mortality. We used the
database developed for the National Morbidity and Mortality Air Pollution Study
to estimate ozone mortality risks in 97 US cities in May through September, 1987
2000. We treated temperature as a confounder as well as an effect modifier by
estimating risks at low, moderate, and high temperature categories. When
temperature was treated as a confounder, a 10-ppb increase in daily 24-h ozone
was associated with a 0.47% (95% CI: 0.19%-0.76%) increase in mortality. When we
assessed effect modification by temperature, the interaction between ozone and
temperature was not statistically significant. However, there was a U-shaped
pattern in mortality risk, which was greater at the low (<25th percentile) and
high (>75th percentile) temperature levels than moderate temperature levels. At
the high temperature category, a 10% increase in AC prevalence mitigated
mortality risk associated with 10-ppb of ozone exposure by -0.18% (95% CI:
0.35%, -0.02%). Furthermore, ozone mortality risk in the high temperature
category increased as we restricted our analyses to hotter days. On days where
temperatures exceeded the 75th, 90th, and 95th percentile temperatures, a 10-ppb
increase in ozone was associated with a 0.65% (95% CI: 0.20%-1.09%), 0.83% (95%
CI: 0.17%-1.48%), and 1.35% (95% CI: 0.44%-2.27%) increase in mortality,
respectively. These results suggested that high temperatures may exacerbate
physiological responses to short-term ozone exposure.
PMID- 25113627
TI - Photosynthesis, chlorophyll fluorescence characteristics, and chlorophyll content
of soybean seedlings under combined stress of bisphenol A and cadmium.
AB - Bisphenol A (BPA) is ubiquitous in the environment because of its continual
application in plastics and the epoxy resin industry. Cadmium (Cd) is a highly
toxic heavy metal element mainly used in smelting, electroplating, and plastic
and dye manufacturing. Pollution as a result of BPA and Cd exists simultaneously
in many agricultural regions. However, little information is available regarding
the combined effects of BPA and Cd on plants. The combined effects of BPA and Cd
on the photosynthesis, chlorophyll fluorescence, and chlorophyll content of
soybean seedlings were investigated using noninvasive technology. Combined
treatment with 1.5 mg/L BPA and 0.2 mg/L Cd synergistically improved the net
photosynthetic rate (Pn ), initial fluorescence (F0 ), maximal photochemical
efficiency (Fv /Fm ), effective quantum yield of photosystem II (PhiPSII ),
photosynthetic electron transport rate (ETR), and chlorophyll content. Combined
treatment with 1.5 mg/L BPA and 3.0 mg/L Cd increased the F0 and decreased the Pn
, Fv /Fm , PhiPSII , and ETR, whereas BPA and Cd exhibited an antagonistic
effect. Furthermore, combined treatment with 17.2/50.0 mg/L BPA and 3.0/10.0 mg/L
Cd synergistically decreased the Pn , Fv /Fm , PhiPSII , ETR, and chlorophyll
content, although it increased the F0 . Finally, the effects of BPA and Cd on
photosynthesis, chlorophyll fluorescence, and chlorophyll content ceased when BPA
stress was stopped.
PMID- 25113628
TI - Intranasally administered serelaxin abrogates airway remodelling and attenuates
airway hyperresponsiveness in allergic airways disease.
AB - BACKGROUND: The peptide hormone relaxin plays a key role in the systemic
hemodynamic and renovascular adaptive changes that occur during pregnancy, which
is linked to its antiremodelling effects. Serelaxin (a recombinant form of human
gene-2 relaxin) has been shown to inhibit lung fibrosis in various disease models
and reverse airway remodelling and airway hyperresponsiveness (AHR) in allergic
airways disease (AAD). OBJECTIVE: Although continuous systemic delivery of
exogenous serelaxin alleviates allergic fibrosis and AHR, more direct routes for
administration into the lung have not been investigated. Thus, intranasal
administration of serelaxin was evaluated for its ability to reverse airway
remodelling and AHR associated with AAD. METHODS: Female Balb/c mice were
subjected to a 9-week model of chronic AAD. Subgroups of animals (n = 12/group)
were then treated intranasally with serelaxin (0.8 mg/mL) or vehicle once daily
for 14 days (from weeks 9-11). Saline-sensitized/challenged mice treated with
intranasal saline served as additional controls. Differential bronchoalveolar
lavage (BAL) cell counts, ovalbumin (OVA)-specific IgE levels, tissue
inflammation, parameters of airway remodelling and AHR were then assessed.
RESULTS: Chronic AAD was associated with significant increases in differential
BAL cell counts, OVA-specific IgE levels, inflammation, epithelial thickening,
goblet cell metaplasia, TGF-beta1 expression, epithelial Smad2 phosphorylation
(pSmad2), subepithelial collagen thickness, total lung collagen concentration and
AHR (all P < 0.05 vs. respective measurements from saline-treated mice). Daily
intranasal delivery of serelaxin significantly diminished AAD-induced epithelial
thickening, epithelial pSmad2, subepithelial and total lung collagen content
(fibrosis) and AHR (all P < 0.05 vs. vehicle-treated AAD mice). CONCLUSIONS AND
CLINICAL RELEVANCE: Intranasal delivery of serelaxin can effectively reduce
airway remodelling and AHR, when administered once daily. Respirable preparations
of serelaxin may have therapeutic potential for the prevention and/or reversal of
established airway remodelling and AHR in asthma.
PMID- 25113629
TI - Experimental investigation of the 2D ion beam profile generated by an ESI
octopole-QMS system.
AB - In this paper, we have employed an ion imaging approach to investigate the
behavior of ions exiting from a quadrupole mass spectrometer (QMS) system that
employs a radio frequency octopole ion guide before the QMS. An in-vacuum active
pixel detector (Timepix) is employed at the exit of the QMS to image the ion
patterns. The detector assembly simultaneously records the ion impact position
and number of ions per pixel in every measurement frame. The transmission
characteristics of the ion beam exiting the QMS are studied using this imaging
detector under different operating conditions. Experimental results confirm that
the ion spatial distribution exiting the QMS is heavily influenced by ion
injection conditions. Furthermore, ion images from Timepix measurements of
protein standards demonstrate the capability to enhance the quality of the mass
spectral information and provide a detailed insight in the spatial distribution
of different charge states (and hence different m/z) ions exiting the QMS.
PMID- 25113630
TI - Subtotal supracricoid laryngectomy: changing in indications, surgical techniques
and use of new surgical devices.
AB - PURPOSE: The aim of this study is to evaluate the evolution of supracricoid
partial laryngectomy (SCPL) in indications, surgical techniques and outcomes
through last decades. MATERIALS AND METHODS: A retrospective analysis of 146
patients affected by laryngeal cancer treated with SCPL was carried on. We
defined: (1) group A, 100 patients treated by cold instruments between 1995 and
2004; (2) group B, 46 patients treated by harmonic scalpel between 2005 and 2010.
Complications rate, and functional and oncological results were documented and a
comparison between the two groups was made; histopathological analysis of
surgical margins was evaluated and correlated with local incidence of recurrence.
RESULTS: Significant differences in age mean-value (p=0.02), T classification
(p=0.007), and in indication for more advanced-staged patients were found in
group B (p=0.001). Surgical procedure was shorter in group B (p<0.001), with
shorter swallowing recovery (p=0.003). Oncological outcomes did not report any
significant differences. Group B showed a higher incidence of post- operative
arytenoid edema (p=0.03) associated with a lower rate of pneumonia (p=0.038).
Despite a higher rate of close or positive-margins found in group B no higher
incidence of local-recurrence was reported (p=0.02) compared to group A.
CONCLUSIONS: We documented changing in indications and surgical technique for
SCPL because of the development of modern diagnostic techniques and the
introduction of low-thermal injury device allowing a more challenging tumor
excision as well as with a shorter swallowing recovery in our series.
PMID- 25113631
TI - Long-term efficacy of inferior meatal antrostomy for treatment of postoperative
maxillary mucoceles.
AB - PURPOSE: Transnasal endoscopic marsupialization has replaced the conventional
Caldwell-Luc operation for managing postoperative maxillary mucoceles. Inferior
meatal antrostomy (IMA) may be an easier and more effective method than middle
meatal antrostomy (MMA) because of anatomical and structural changes of the
maxillary sinus. We evaluated the long-term efficacy and technical simplicity of
both methods. METHODS: This study included 21 and 32 patients who underwent MMA
and IMA, respectively. They were diagnosed with a unilateral postoperative
maxillary mucocele, and medical records were reviewed for history, clinical
presentation, radiographic findings, surgical intervention, complications, and
outcomes. During follow-up, the size of the opening and stenosis or obstruction
of the antrostomy site were evaluated. RESULTS: Preoperative symptoms and mean
follow-up period were similar in both groups. All patients in the IMA group
received the operation as planned, whereas in four MMA patients, the attempt to
create an opening failed because of thick bones and anatomical changes from the
previous operation; in these patients, IMA was performed. The opening remained
large enough for ventilation and drainage between the mucocele and the nasal
cavity in both groups. There were no major complications, such as profuse
bleeding, wound infection, or orbital or nasolacrimal duct injury. CONCLUSIONS:
Although both surgical procedures seem to be effective for managing postoperative
maxillary mucoceles, IMA is easier to perform, and no instances of failure to
create antrostomy openings occurred. We recommend IMA as the surgical technique
of choice, but providing an opening of sufficient size is necessary to ensure
long-term efficacy.
PMID- 25113633
TI - Improving complex kinship analyses with additional STR loci.
AB - In a standard paternity testing, mother, child, and alleged father are analyzed
with STR markers using commercially available kits. Since Italian civil
legislation does not have thresholds to confirm a paternity, paternity is
practically proven when likelihood ratio increases prior probability of paternity
to posterior, accepted by court as sufficient. However, in some cases the number
of markers included in a commercial kit may be insufficient to conclusively prove
or disprove a relationship between individuals, especially when complex family
scenarios are suspected or indirect analyses are required. Additional genetic
information can increase the values of the likelihood ratio regarding the
detection of true parental relationships in a pedigree, while reducing the
chances of false attributions (e.g. false paternities). In these cases the
introduction of a 26Plex amplification system allows to examine 23-26 additional
markers depending on the commercial kit used, thus increasing the statistical
power of the kinship analysis. The PCR conditions were optimized for a multiplex
amplification system and a new generation CE instrument. In order to demonstrate
the utility of additional STRs markers, four complex kinship cases are presented.
PMID- 25113632
TI - Linking mother and youth parenting attitudes: indirect effects via maltreatment,
parent involvement, and youth functioning.
AB - Evidence suggests that parenting attitudes are transmitted within families.
However, limited research has examined this prospectively. The current
prospective study examined direct effects of early maternal attitudes toward
parenting (as measured at child age 4 by the Adult-Adolescent Parenting Inventory
[AAPI]) on later youth parenting attitudes (as measured by the AAPI at youth age
18). Indirect effects via child maltreatment (physical abuse, sexual abuse,
neglect, and emotional maltreatment), parent involvement, and youth functioning
(internalizing and externalizing problems) were also assessed. Analyses were
conducted on data from 412 families enrolled in the Longitudinal Studies of Child
Abuse and Neglect (LONGSCAN). There were significant direct effects for three of
the four classes of mother parenting attitudes (appropriate developmental
expectations of children, empathy toward children, and appropriate family roles)
on youth attitudes but not for rejection of punishment. In addition, the
following indirect effects were obtained: Mother expectations influenced youth
expectations via neglect; mother empathy influenced youth empathy via both
parental involvement and youth externalizing problems; and mother rejection of
punishment influenced youth rejection of punishment via youth internalizing
problems. None of the child or family process variables, however, affected the
link between mother and youth attitudes about roles.
PMID- 25113634
TI - Weaknesses of histological analysis in celiac disease diagnosis: new possible
scenarios.
AB - INTRODUCTION: Celiac disease (CD) is an autoimmune disorder triggered by the
ingestion of gluten. Serology and organ culture system can support CD diagnosis,
despite histology being the gold standard. AIM: We wanted to test the uniformity
of application of Marsh-Oberhuber criteria by five different histologists. We
also compared histological and serological data with cultural results to consider
new possible strategies in CD diagnosis. METHODS: We studied 114 patients, who
were divided in two groups. Group A was composed of 66 patients on a gluten
containing diet, with gluten-related signs and symptoms, showing positive
serological anti-endomysial antibodies (EMA) and anti-tissue transglutaminase
(anti- tTG). Group B was composed of 48 disease-control patients, presenting
serological EMA and anti-tTG negative results. All patients studied underwent
esophagogastroduodenoscopy with duodenal biopsy and duodenal mucosa organ
culture. All histological samples were evaluated by five different histologists
according to an appropriate questionnaire following Marsh-Oberhuber
classification. Cohen kappa inter-test was used for evaluating the agreement
between histologists regarding group A. RESULTS: Strength of agreement was
fair/moderate for villous:crypt ratio, moderate/good for villous height and crypt
depth, and poor for intraepithelial lymphocytosis. Patients belonging to group A
presented positive serological as well as cultural results in 100% of cases. None
of the patients belonging to group B presented serological or cultural positive
results. DISCUSSION: Our study stresses the limits of histological interpretation
due to the lack of uniformity in the use of Marsh-Oberhuber classification. These
findings could cast doubt on the role of histology as CD gold standard and could
open a debate on the most appropriate CD diagnostic procedure.
PMID- 25113635
TI - Host defense peptides: front-line immunomodulators.
AB - Although first studied for their antimicrobial activity, host defense peptides
(HDPs) are now widely recognized for their multifunctional roles in both the
innate and adaptive immune responses. Their diverse immunomodulatory capabilities
include the modulation of pro- and anti-inflammatory responses, chemoattraction,
enhancement of extracellular and intracellular bacterial killing, cellular
differentiation and activation of the innate and adaptive compartments, wound
healing, and modulation of autophagy as well as apoptosis and pyroptosis. We
review the various immunomodulatory roles of HDPs and their synthetic analogs,
the innate defense regulators (IDRs). We discuss their potential as host-directed
therapies, the hurdles they face in clinical development, and propose ways
forward.
PMID- 25113636
TI - Long non-coding RNAs in the regulation of the immune response.
AB - It is increasingly clear that long non-coding RNAs (lncRNAs) regulate a variety
biological responses, and that they do so by a diverse range of mechanisms. In
the field of immunology, recent publications have shown widespread changes in the
expression of lncRNAs during the activation of the innate immune response and T
cell development, differentiation, and activation. These lncRNAs control
important aspects of immunity such as production of inflammatory mediators,
differentiation, and cell migration through regulating protein-protein
interactions or via their ability to basepair with RNA and DNA. We review the
current understanding of the mechanism of action of these immune-related lncRNAs,
discuss their impact on physiological and pathological processes, and highlight
important areas of inquiry at the intersection between immunology and lncRNA
biology.
PMID- 25113637
TI - Influence of the microbiota on vaccine effectiveness.
AB - Studies of the relationship between the microbiome and the development and
function of the immune system are demonstrating novel concepts that could
significantly alter the way we treat disease and promote wellness. Several
diseases, including inflammatory bowel disease, allergy/asthma, and diabetes, are
associated with changes in composition of the microbiome. Recent findings suggest
novel complex mechanisms by which the microbiome impacts immune cell development
and differentiation. A major implication of these findings is that the
composition of microbiome may ultimately affect vaccine efficacy. We explore here
the potential role of the microbiome in vaccine responses in the context of our
growing understanding of the relationship between the gastrointestinal
microbiota, resident immune cell populations, and systemic immunity.
PMID- 25113640
TI - Expression and localization of estrogen receptor in human breast cancer and its
clinical significance.
AB - The aim of this study was to analyze the clinicopathologic significance of
ERalpha protein that localized in the cell cytoplasm and/or cell membrane of
human breast cancer and explore what kind of protein that the cytoplasm/membrane
ERalpha belongs to. ERalpha expressions in 61 cases of breast cancer are detected
by immunohistochemistry, grouping is performed according to the positive staining
of different subcellular localizations, the expression levels of ERalpha66 and
ERalpha36 in cancer tissues of groups with different subcellular localizations
are detected by Western blot, and correlation between the indicators and its
clinicopathologic significance are analyzed by combining with the clinical
pathological parameters. Localization by immunohistochemical staining in breast
cancer cells shows that there are two types of ERalpha-in the cell nucleus and/or
the cell membrane; there are four groups as ER nuclear staining positive +
membrane staining positive (N+/C+), 23 cases; ER nuclear staining positive +
membrane staining negative (N+/C-), 16 cases; ER nuclear staining negative +
membrane staining positive (N-/C+), 8 cases; and ER nuclear staining negative +
membrane staining negative (N+/C+), 14 cases. ER expression in the cytoplasm
and/or membrane of cancer cells is correlated with the high expression of HER-2,
the lymphatic metastasis, and the late clinical stage. Western blot results show
that ER protein in breast cancer tissues mainly consists of ERalpha66 and
ERalpha36 bands, and among all the groups, all the cases from the N+/C+ group (n
= 23) have both ERalpha66 and ERalpha36 expressions; in the N+/C- group, 14 cases
of which only have the ERalpha66 expression without ERalpha36 expression and 2
cases of which have both ERalpha66 and ERalpha36 expression; all the cases from
the N-/C+ group have only the ERalpha36 expression without ERalpha66 expression;
and in the N-/C- group, there is no either ERalpha66 or ERalpha36 expression. The
expression level of ERalpha36 relates to the age of patients, the menopause, the
lymphatic metastasis, and the tumor size (p < 0.05), and no statistical
significance was shown between it and the family history of patients as well as
the clinical staging parameters (p > 0.05). The expression level of ERalpha66
relates to the tumor size of breast cancer and the clinical stages (p < 0.05),
and no statistical significance was shown between it and the age of patients, the
history of menopause, and the family history as well as the parameters of
lymphatic metastasis (p > 0.05). ER protein expression of human breast cancer is
localized in the cell nucleus and/or the cell membrane, with poor prognosis of
cytoplasm/membrane-positive patients; ER protein that localized in the nucleus is
mainly ERalpha66 and that localized in the cytoplasm and/or membrane is mainly
ERalpha36.
PMID- 25113638
TI - Prostaglandin D2-supplemented "functional eicosanoid testing and typing" assay
with peripheral blood leukocytes as a new tool in the diagnosis of systemic mast
cell activation disease: an explorative diagnostic study.
AB - BACKGROUND: Systemic mast cell activation disease (MCAD) is characterized by an
enhanced release of mast cell-derived mediators, including eicosanoids, which
induce a broad spectrum of clinical symptoms. Accordingly, the diagnostic
algorithm of MCAD presupposes the proof of increased mast cell mediator release,
but only a few mediators are currently established as routine laboratory
parameters. We thus initiated an explorative study to evaluate in vitro typing of
individual eicosanoid pattern of peripheral blood leukocytes (PBLs) as a new
diagnostic tool in MCAD. METHODS: Using the "functional eicosanoid testing and
typing" (FET) assay, we investigated the balance (i.e. the complex pattern of
formation, release and mutual interaction) of prostaglandin E2 (PGE2) and peptido
leukotrienes (pLT) release from PBLs of 22 MCAD patients and 20 healthy
individuals. FET algorithms thereby consider both basal and arachidonic acid (AA)
, acetylsalicylic acid (ASA)-, and substance P (SP)-triggered release of PGE2 and
pLT. The FET assay was further supplemented by analyzing prostaglandin D2 (PGD2),
as mast cell-specific eicosanoid. RESULTS: We observed marked PGE2-pLT imbalances
for PBLs of MCAD patients, as indicated by a markedly enhanced mean FET value of
1.75 +/- 0.356 (range: 1.14-2.36), compared to 0.53 +/- 0.119 (range: 0.36-0.75)
for healthy individuals. In addition, mean PGD2 release from PBLs of MCAD
patients was significantly, 6.6-fold higher than from PBLs of healthy individuals
(946 +/- 302.2 pg/ml versus 142 +/- 47.8 pg/ml; P < 0.001). In contrast to
healthy individuals, PGD2 release from PBLs of MCAD patients was markedly
triggered by SP (mean: 1896 +/- 389.7 pg/ml; P < 0.001), whereas AA and ASA
caused individually varying effects on both PGD2 and pLT release. CONCLUSIONS:
The new in-vitro FET assay, supplemented with analysis of PGD2, demonstrated that
the individual patterns of eicosanoid release from PBLs can unambiguously
distinguish MCAD patients from healthy individuals. Notably, in our analyses, the
FET value and both basal and triggered PGD2 levels were not significantly
affected by MCAD-specific medication. Thus, this approach may serve as an in
vitro diagnostic tool to estimate mast cell activity and to support
individualized therapeutic decision processes for patients suffering from MCAD.
PMID- 25113641
TI - New insight into improvement of cardiovascular outcomes with intensive glycemic
control in patients with metabolic syndrome and type 2 diabetes mellitus
included.
AB - The epidemiology of metabolic syndrome (MetS) is very concerning since this is a
widespread chronic disease in adult and elderly population. Different
epidemiological studies confirmed strong relationship between type 2 diabetes
mellitus (DM2) inclusive MetS and the occurrence of microvascular and
macrovascular complications in these patients. Therefore, we are discussing
molecular mechanisms and pathways recently introduced and intensively researched.
These molecules have been held responsible for direct and indirect correlative
trends important in the assessment of potential benefit of intensive glycemic
control. Novel substances may improve patient's outcome in recent future
regarding cardiovascular complications though their acting mechanisms have not
been completely elucidated. We are reviewing whether it would intensive glycemic
control be a reasonable approach in patients with MetS when DM2 is included and
which recommendations are currently widely applied. The aim was therefore to
emphasize current need for further investigations in the field since the utility
of intensive glycemic control in all DM/MetS patients as mean for reduction of
cardiovascular complications still remains controversial.
PMID- 25113639
TI - Tumor Necrosis Factor Alpha (-238 / -308) and TNFRII-VNTR (-322) Polymorphisms as
Genetic Biomarkers of Susceptibility to Develop Cervical Cancer Among Tunisians.
AB - Host genetic factors may confer susceptibility to Cervical Cancer. TNF-alpha as
pro-inflammatory cytokine participates in the maintenance of immune homeostasis.
Allelic variation of immuno-modulatory genes is associated with alteration in
immune function. This study investigated the associations between TNF-alpha
308G>A, -238G>A, and TNFRII - VNTR-322 and cervical cancer in Tunisian women.
Genotypes of those polymorphisms were detected in 130 cases and 260 controls. The
variant heterozygote -308 G/A was associated with a 41% decreased risk of
cervical cancer (GG vs A/A; p = 0.002; OR = 0.41; 95% CI =0.23-0.76).
Furthermore, compared with dominant variant G/G, the (G/A+A/A) genotypes was
significantly associated with a decreased risk of CC (GG vs G/A+A/A; p = 0.026;
OR = 0.62; 95% CI = 0.40-0.97). The FIGO stratified analysis showed that the
minor variant A/A and combined G/A+A/A of TNFalpha-238 G>A and TNFalpha-308 G>A
increased the risk of the tumor evolution, respectively, (P = 0.011; OR = 2.98;
95% CI = 1.16-7.72) (P = 0.008; OR = 2.76; 95% CI = 1.20-6.41), (P = 0.000; OR =
16.33; 95% CI = (5.10-55.23) (P = 0.000; OR = 7.54; 95% CI = 2.68-22.29). There
was statistically significant relationship between the incidence of the TNF-alpha
mutations and the clinical progression of cancer according to the FIGO
classification. In our study, the haploview analysis revealed no LD between
rs1800629 and rs361525. TNF-alpha and TNFRII polymorphisms might be genetic risk
factors for cervical cancer in Tunisian population.
PMID- 25113642
TI - Relation of PAI-1 and TPA genes polymorphisms to acute myocardial infarction and
its outcomes in Egyptian patients.
AB - Endogenous fibrinolysis is a protective mechanism against arterial thrombotic
occlusion, which would otherwise lead to permanent tissue damage as acute
myocardial infarction (AMI). We aimed to investigate the association of
plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (TPA)
genes polymorphisms with myocardial infarction and its outcomes in Egyptian
patients. 184 patients with AMI and 184 controls were included in the study. PAI
1 and TPA genes polymorphisms were analyzed by polymerase chain reaction. All
patients were followed for AMI complications during their hospitalization. We
found a significant association among TPA ID, II genotypes, and I allele and
increased risk of AMI by 2.1, 3.2, and 1.9 fold, respectively. Also, the
frequencies of PAI-1 4G/4G genotype and 4G allele were significantly increased in
patients with AMI as compared to the control group. Furthermore, AMI patients
with PAI-1 4G/4G genotype were significantly more likely to have morbidity and
mortality complications as compared to AMI patients without complications (P =
0.00 and 0.048, respectively). We concluded that 4G/4G genotype and 4G allele of
the PAI-1 gene are associated with risk of AMI and its morbidity. The PAI-1 4G/4G
genotype is associated with mortality of AMI. There is also an association
between TPA ID, II genotypes, and I allele with increased risk of AMI.
PMID- 25113643
TI - Posterior trochanteric osteotomy in acetabular fractures for 32 cases.
AB - The aim of this study is to explore the method and clinical outcome of posterior
trochanteric osteotomy in acetabular fractures. From January 2000 to January
2008, 32 cases of acetabular fractures involving the dome of acetabulum underwent
posterior trochanteric osteotomy for a better exposure and internal fixation with
acetabular tridimensional memory fixation system. 28 cases (16 men and 12 women,
mean age 39.9 years, range 16-73 years) were followed up with an average of 48.9
months (range of 19-95 months) and four were lost during follow up. Of 28 cases,
19 were fresh fractures and 9 were old fractures. The reduction was evaluated
with Matta criteria. Clinical evaluation was based on modified Merle d'Aubigne
and Postel scoring. Motor strength of the abductors was evaluated according to
the Medical Research Council grading system. Ectopic ossification was classified
according to Brooker criteria. Anatomical reduction was achieved in 17 cases and
satisfied reduction in 10 patients. Poor reduction happened in an old fracture.
All acetabular fractures got a direct bone union and no displacement and deep
infection occurred. All osteotomies healed within 3.5 months without any
nonunion, proximal migration of the greater trochanter, loosing or broken of
instrumentation, and deep infection. Two superficial infections were healed with
a regular dressing. Two patients underwent removal of implants from greater
trochanter because of irritation. The strength of the abductors was of Grade 3/5
in two patients, Grade 4/5 in five patients, and normal in the rest. Clinical
scoring was excellent to good in 84 %. Ectopic ossification occurred in five
patients, grade 1 in two patients, grade 2 in two, and grade 3 in one. But
function of hip joint was not seriously affected. Posterior trochanteric
osteotomy can provide an adequate exposure of the dome of acetabulum without the
associated complications like nonunion, proximal replacement, and weak of the
abductors which often occur with standard oblique osteotomy.
PMID- 25113644
TI - Gold-catalyzed cycloisomerization of 1,6,8-dienyne carbonates and esters to cis
cyclohepta-4,8-diene-fused pyrrolidines.
AB - A synthetic approach that provides access to cis-cyclohepta-4,8-diene-fused
pyrrolidines efficiently through Au(I) -catalyzed cycloisomerization of 1,6,8
dienyne carbonates and esters at a low catalyst loading of 2 mol % is reported.
Starting carbonates and esters with a pendant alkyl group on the terminal alkenyl
carbon center were found to favor tandem 1,2-acyloxy migration/cyclopropanation
followed by Cope rearrangement of the resulting cis-3-azabicyclo[3.1.0]hexane
intermediate. On the other hand, substrates containing a terminal diene or
starting materials in which the distal alkene moiety bears a phenyl substituent
were observed to undergo competitive but reversible 1,3-acyloxy migration prior
to the nitrogen-containing bicyclic ring formation. The delineated reaction
mechanism also provides experimental evidence for the reversible interconversion
between the oft-proposed organogold intermediates obtained in this step of the
tandem process.
PMID- 25113645
TI - Aging and the novelty pressor effect in men on the first day of 7-day/24-hour
ambulatory blood pressure monitoring.
PMID- 25113646
TI - Elevated serum CA 19-9 at screening tests: underlying conditions and role of
abdominopelvic CT.
AB - OBJECTIVES: To investigate underlying conditions of patients with elevated CA 19
9 at screening tests and to evaluate diagnostic performance of abdominopelvic CT.
METHODS: One hundred and thirteen patients with elevated CA 19-9 (>37 U/ml) who
underwent abdominopelvic CT in a screening program were selected. Underlying
conditions were determined by reviewing all available data and follow-up records.
Patients were categorized into malignancy, benign, and normal/non-related disease
groups. Their mean CA 19-9 and percent of patients with CA 19-9 >= 100 U/ml were
compared. Diagnostic sensitivity of CT for detecting underlying conditions of
elevated CA 19-9 was analysed. RESULTS: Seventeen patients (17/113, 15 %) had 17
elevated CA 19-9-related malignancies, and 55 patients (55/113, 48.7 %) had 70
benign diseases. Mean CA 19-9 and percent of patients with CA 19-9 >= 100 U/ml in
the malignancy group were significantly higher than in the two other groups. CT
detected all except one malignant lesion with a detection sensitivity of 94.1 %
(16/17). Of 70 CA 19-9-related benign diseases, CT detected 34 benign diseases
(48.6 %) providing an alternative diagnosis for elevated CA 19-9. CONCLUSION:
Abdominopelvic CT is not only useful in detecting malignancies, but can also
diagnose alternative benign causes of elevated CA 19-9 in asymptomatic screening
tests. KEY POINTS: * Fifteen percent of asymptomatic patients with elevated CA19
9 may have intra-abdominal malignancies. * Mean value of CA19-9 is different
among malignant, benign, and non-related groups. * CT shows excellent sensitivity
for intra-abdominal malignancies as causatives of elevated CA19-9. * CT provides
alternative benign diagnoses as causatives of elevated CA19-9. * Detection of
causatives of elevated CA19-9 using CT alleviates concerns and uncertainty.
PMID- 25113647
TI - Diffusion-weighted imaging for the detection of mesenteric small bowel tumours
with Magnetic Resonance--enterography.
AB - PURPOSE: To retrospectively investigate the added value of diffusion-weighted MR
imaging (DWI) for detecting mesenteric small bowel tumours (MSBTs) via MR
enterography. MATERIALS AND METHODS: MR-enterographies of 98 patients with
suspected MSBTs were blindly analyzed by two independent readers for the presence
of MSBTs. Four imaging sets including "standard" (Haste and TrueFisp), "standard
+ DWI," "standard + gadolinium-enhanced" and "standard + DWI + gadolinium
enhanced" were reviewed. Diagnostic performance of different readings were
compared with McNemar's test. RESULTS: Twenty-nine MSBTs were pathologically
confirmed. For R1 (junior radiologist) sensitivity, specificity, PPV, NPV and
accuracy for the detection of MSBTs via standard MRI were 52 % [95 % CI: 34 %-70
%] (15/29), 94 % [95 % CI: 89 %-100 %] (65/69), 79 % [95 % CI: 61 %-97 %]
(15/19), 82 % [95 % CI: 74 %-91 %] (65/79) and 82 % [95 % CI: 74 %-89 %] (80/98),
respectively. For R2 (senior radiologist) they were 76 % [95 % CI: 60 %-91 %]
(22/29), 96 % [95 % CI: 91-100 %] (66/69), 88 % [95 % CI: 75 %-100 %] (22/25), 90
% [95 % CI: 84 %-97 %] (66/73) and 90 % [95 % CI: 84 %-96 %] (88/98),
respectively. Adding DWI they were 72 % [95 % CI: 56 %-89 %] (21/29), 91 % [95 %
CI: 85 %-98 %] (63/69), 78 % [95 % CI: 62 %-94 %] (21/27), 89 % [95 % CI: 81 %-96
%] (63/71) and 87 % [95 % CI: 80 %-94 %] (85/98) for R1 and 79 % [95 % CI: 65 %
94 %] (23/29), 97 % [95 % CI: 93 %-100 %] (67/69), 92 % [95 % CI: 81 %-100 %]
(23/25), 92 % [95 % CI: 86 %-98 %] (67/73) and 92 % [95 % CI: 86 %-97 %] (90/98)
for R2. Sensitivities for tumour detection were higher after adding DWI to
standard MRI, although only for R1 was this significant (P = 0.03). Adding DWI to
standard + gadolinium-enhanced MRI did not significantly increase MR performance.
CONCLUSION: DWI improves MSBT detection via MR-enterography compared to standard
unenhanced MR-enterography, especially for unexperienced readers. KEY POINTS: *
MR-enterography is accurate for the detection of mesenteric small-bowel tumours.
* Diffusion-weighted sequencing helps inexperienced readers detect small-bowel
tumours with MR-enterography. * Diffusion-weighted sequencing adds value to
standard MR-enterography when gadolinium is contraindicated.
PMID- 25113648
TI - Diagnostic performance of shear wave elastography in the identification of
malignant thyroid nodules: a meta-analysis.
AB - OBJECTIVE: This meta-analysis aimed to assess the performance of shear wave
elastography (SWE) in the identification of malignant thyroid nodules. METHODS:
Web of Science, Scopus, PubMed, and the references of narrative reviews were
searched for relevant studies with a publication date through October 2013. The
methodological quality was assessed using QUADAS tools. Data synthesis was
calculated using the bivariate mixed-effects regression model. RESULTS: Of the
131 studies identified, 15 (11.5 %) were included, in which SWE, point-SWE or 2D
SWE, was used to evaluate 1,867 thyroid nodules in 1,525 patients. Methodological
assessment revealed study quality was moderate to high. The pooled sensitivity,
specificity, and area under the summary receiver operating characteristic curve
of SWE for detecting malignant thyroid nodules were 84.3 % (95 % confidence
interval [CI], 76.9-89.7 %), 88.4 % (95 % CI, 84.0-91.7 %), and 93 % (95 % CI, 90
95 %), respectively. As a screening tool, positive and negative predictive values
were 27.7-44.7 % and 98.1-99.1 %, respectively, calculated with a malignance
prevalence of 5-10 % in thyroid nodules. A publication bias regression test
revealed no significant small-study bias. CONCLUSIONS: SWE is a highly accurate
diagnostic modality for the identification of malignant thyroid nodules, with
promise for integration into routine imaging protocols for thyroid nodules. KEY
POINTS: * Shear wave elastography (SWE) is a group of novel ultrasound-based
technologies. * Meta-analysis was employed to assess relevant studies of SWE of
thyroid nodules. * SWE had high sensitivity and specificity in identifying
malignant thyroid nodules. * The high negative predictive value of SWE can reduce
unnecessary biopsies.
PMID- 25113649
TI - Quantitative assessment of right ventricular function and pulmonary regurgitation
in surgically repaired tetralogy of Fallot using 256-slice CT: comparison with 3
Tesla MRI.
AB - OBJECTIVES: To compare 256-slice cardiac computed tomography (CCT) with cardiac
magnetic resonance (CMR) imaging to assess right ventricular (RV) function and
pulmonary regurgitant fraction (PRF) in patients with repaired tetralogy of
Fallot (TOF). METHODS: Thirty-three consecutive patients with repaired TOF
underwent retrospective ECG-gated CCT and 3-Tesla CMR. RV and left ventricular
(LV) end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV)
and ejection fraction (EF) were measured using CCT and CMR. PRF-CCT (%) was
defined as (RVSV - LVSV)/RVSV. PRF-CMR (%) was measured by the phase-contrast
method. Repeated measurements were performed to determine intra- and
interobserver variability. RESULTS: CCT measurements, including PRF, correlated
highly with the CMR reference (r = 0.71-0.96). CCT overestimated RVEDV (mean
difference, 17.1 +/- 2.9 ml), RVESV (12.9 +/- 2.1 ml) and RVSV (4.2 +/- 2.0 ml),
and underestimated RVEF (-2.6 +/- 1.0%) and PRF (-9.1 +/- 2.0%) compared with
CMR. The limits of agreement between CCT and CMR were in a good range for all
measurements. The variability in CCT measurements was lower than those in CMR.
The estimated effective radiation dose was 7.6 +/- 2.6 mSv. CONCLUSIONS: 256
slice CCT can assess RV function and PRF with relatively low dose radiation
exposure in patients with repaired TOF, but overestimates RV volume and
underestimates PRF. KEY POINTS: 256-slice CT assessment of RV function is highly
reproducible in repaired TOF. Pulmonary regurgitation can be evaluated by
biventricular systolic volume difference. CT overestimates RV volume and
underestimates pulmonary regurgitation, compared with MRI.
PMID- 25113650
TI - A new technique for noise reduction at coronary CT angiography with multi-phase
data-averaging and non-rigid image registration.
AB - OBJECTIVES: To investigate the feasibility of a newly developed noise reduction
technique at coronary CT angiography (CTA) that uses multi-phase data-averaging
and non-rigid image registration. METHODS: Sixty-five patients underwent coronary
CTA with prospective ECG-triggering. The range of the phase window was set at 70
80% of the R-R interval. First, three sets of consecutive volume data at 70%, 75%
and 80% of the R-R interval were prepared. Second, we applied non-rigid
registration to align the 70% and 80% images to the 75% image. Finally, we
performed weighted averaging of the three images and generated a de-noised image.
The image noise and contrast-to-noise ratio (CNR) in the proximal coronary
arteries between the conventional 75% and the de-noised images were compared. Two
radiologists evaluated the image quality using a 5-point scale (1, poor; 5,
excellent). RESULTS: On de-noised images, mean image noise was significantly
lower than on conventional 75% images (18.3 HU +/- 2.6 vs. 23.0 HU +/- 3.3, P <
0.01) and the CNR was significantly higher (P < 0.01). The mean image quality
score for conventional 75% and de-noised images was 3.9 and 4.4, respectively (P
< 0.01). CONCLUSIONS: Our method reduces image noise and improves image quality
at coronary CTA. KEY POINTS: * We introduce a new method for image noise
reduction at cardiac CT. * Multiple data acquisitions of an object and their
averaging yield lower noise. * Our method uses multi-phase images reconstructed
from unused redundant imaging data. * It reduces image noise by averaging multi
phase images transformed by non-rigid registration. * This method achieves a 20%
image noise reduction at cardiac CT.
PMID- 25113651
TI - Ethical issues for late-stage trials of multipurpose prevention technologies for
HIV and pregnancy.
AB - Multipurpose prevention technologies (MPTs) designed to simultaneously prevent
pregnancy and HIV could provide urgently needed tools to address unmet sexual and
reproductive health needs of women worldwide. Late-stage clinical trials will be
complex given the need to demonstrate efficacy for HIV and contraceptive
indications simultaneously from a single product. Currently, HIV and pregnancy
prevention trials have distinctive design features that will need to be
reconciled in MPT trials. This article identifies several ethical issues uniquely
associated with this research that will benefit from future deliberation and
guidance to ensure that this globally important research can proceed efficiently
and expeditiously.
PMID- 25113652
TI - Prediction of domestic violence against married women in southwestern Turkey.
AB - OBJECTIVE: To determine the prevalence of, and independent risk factors for
various domestic violence categories among married women of reproductive age in
southwestern Turkey. METHODS: The present cross-sectional study included 260
randomly selected women registered to a family physician in the district of
Gonen, Isparta. During home visits between October 1 and December 31, 2012, the
women completed a questionnaire that included between four and eight questions
for each violence category (physical, verbal, economic, emotional, and sexual) to
assess the lifetime presence of domestic violence. Logistic regression models
with backward elimination were constructed to define independent risk factors for
domestic violence. RESULTS: In total, 176 (67.7%) women reported any type of
domestic violence at least once in their lifetime. Verbal/psychological abuse was
the most frequent type (reported by 121 [46.5%] women). Living in a village,
young age (19-29 years) of the husband, adolescent age (<19 years) of the husband
at marriage, and problem alcohol use or problem gambling in the partner were
independent predictors of domestic violence. CONCLUSION: Attention should be
given to area of residence, age of both partners at marriage, adolescent
marriage, and husband characteristics during screening for domestic violence.
PMID- 25113653
TI - Relationship between serum gamma-glutamyltransferase levels and prehypertension
in Chinese adults: the cardiometabolic risk in Chinese study.
AB - The authors aimed to investigate the relationship between serum gamma
glutamyltransferase (GGT) and prehypertension, as well as the modification of
other metabolic risk factors in a large cohort of Chinese individuals. The data
were collected via a community-based health examination survey in central China.
Blood pressure, body mass index (BMI), and levels of GGT, fasting blood glucose,
aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lipid
indicators were measured. In total, data from 18,302 patients with available
biomarkers were included in the present study. Elevated blood pressure was
associated with increased GGT concentration (P<.001). After adjusting for age,
sex, BMI, fasting blood glucose, lipid indicators, AST, and family history of
hypertension, the association between GGT levels and prehypertension remained
significant (P=.021). The adjusted odds ratios (95% confidence interval) for
prehypertension across quintiles of GGT level were 1.00, 1.057 (1.012-1.334),
1.068 (0.916-1.254), 1.024 (0.851-1.368), and 1.272 (1.027-1.593), respectively.
In stratified analyses, the association between GGT levels and prehypertension
was significant in women but was not significant in men. Moreover, additive
effect of BMI and age on the effect of GGT levels on prehypertension (both P for
interaction <.001) was observed. In summary, GGT levels were positively
associated with prehypertension in women, independent of other metabolic factors.
Furthermore, BMI and age may amplify the effects of GGT levels on
prehypertension. These findings suggest that monitoring the levels of GGT could
help in the diagnosis and monitoring of prehypertension.
PMID- 25113657
TI - A brief history of cancer: age-old milestones underlying our current knowledge
database.
AB - This mini-review chronicles the history of cancer ranging from cancerous growths
discovered in dinosaur fossils, suggestions of cancer in Ancient Egyptian papyri
written in 1500-1600 BC, and the first documented case of human cancer 2,700
years ago, to contributions by pioneers beginning with Hippocrates and ending
with the originators of radiation and medical oncology. Fanciful notions that
soon fell into oblivion are mentioned such as Paracelsus and van Helmont
substituting Galen's black bile by mysterious ens or archeus systems. Likewise,
unfortunate episodes such as Virchow claiming Remak's hypotheses as his own
remind us that human shortcomings can affect otherwise excellent scientists.
However, age-old benchmark observations, hypotheses, and practices of historic
and scientific interest are underscored, excerpts included, as precursors of
recent discoveries that shaped modern medicine. Examples include: Petit's total
mastectomy with excision of axillary glands for breast cancer; a now routine
practice, Peyrilhe's ichorous matter a cancer-causing factor he tested for
transmissibility one century before Rous confirmed the virus-cancer link, Hill's
warning of the dangers of tobacco snuff; heralding today's cancer pandemic caused
by smoking, Pott reporting scrotum cancer in chimney sweepers; the first proven
occupational cancer, Velpeau's remarkable foresight that a yet unknown
subcellular element would have to be discovered in order to define the nature of
cancer; a view confirmed by cancer genetics two centuries later, ending with
Rontgen and the Curies, and Gilman et al. ushering radiation (1896, 1919) and
medical oncology (1942), respectively.
PMID- 25113654
TI - Ultrasound imaging of the trapeziometacarpal articular cavity to investigate the
presence of intraarticular gas bubbles after chiropractic manipulation.
AB - OBJECTIVE: The purpose of this study was to investigate the presence of
intraarticular gas bubbles in the trapeziometacarpal joint cavity after
chiropractic manipulation with audible cavitation and to assess the state of the
gas bubbles after a 20-minute refractory period. METHODS: This investigation
included 18 asymptomatic male and female participants between the ages of 21 and
26 years. High-resolution (15 MHz) sonograms of the trapeziometacarpal articular
cavity were obtained by an experienced musculoskeletal ultrasonographer at 3
intervals: premanipulation, within 30 seconds postmanipulation, and at 20 minutes
postmanipulation. The sonograms were saved as digital copies for subsequent
reports that were correlated with reports compiled during dynamic visualization
of the articular cavity. Data were extracted from the reports for analysis.
RESULTS: The premanipulative sonograms showed that 27.78% of joints contained
minute gas bubbles, also known as microcavities, within the synovial fluid before
the joint was manipulated. The remaining 72.22% of joints contained no
intraarticular microcavities. All of the postmanipulative sonograms revealed
numerous large conspicuous gas bubbles within the synovial fluid. The
postrefractory sonograms showed that, in 66.66% of the synovial fluid, gas
bubbles were still visible, whereas the remaining 33.34% had no presence of gas
bubbles or microcavities, and the synovial fluid had returned to its
premanipulative state. CONCLUSION: The findings of this study suggest that
synovial fluid may contain intraarticular microcavities even before a
manipulation is performed. Numerous large intraarticular gas bubbles are formed
during manipulation due to cavitation of the synovial fluid and were observed in
the absence of an axial distractive load at the time of imaging. In most cases,
these gas bubbles remained within the joint for longer than 20 minutes.
PMID- 25113655
TI - Paediatric hereditary angioedema: a survey of UK service provision and patient
experience.
AB - Hereditary angioedema (HAE) is a rare disease characterized by episodes of
potentially life-threatening angioedema. For affected children in the United
Kingdom, there are relatively few data regarding disease prevalence, service
organization and the humanistic burden of the disease. To improve knowledge in
these areas, we surveyed major providers of care for children with HAE. A
questionnaire was sent to major paediatric centres to determine patient numbers,
symptoms, diagnostic difficulties, management and available services. In
addition, all patients at a single centre were given a questionnaire to determine
the experiences of children and their families. Sixteen of 28 centres responded,
caring for a total of 111 UK children. Seven children had experienced life
threatening crises. One-third of patients were on long-term prophylactic
medication, including C1 inhibitor prophylaxis in four children. Eight centres
reported patients who were initially misdiagnosed. Broad differences in
management were noted, particularly regarding indications for long-term
prophylaxis and treatment monitoring. We also noted substantial variation in the
organization of services between centres, including the number of consultants
contributing to patient care, the availability of specialist nurses, the
availability of home therapy training and the provision of patient information.
Ten of 12 patient/carer questionnaires were returned, identifying three common
themes: the need to access specialist knowledge, the importance of home therapy
and concerns around the direct effect of angioedema on their life. To our
knowledge, this study represents the first dedicated survey of paediatric HAE
services in the United Kingdom and provides useful information to inform the
optimization of services.
PMID- 25113658
TI - Phase II drugs currently being investigated for the treatment of hypogonadism.
AB - INTRODUCTION: Hypogonadism is the most common endocrine disorder, which affects
men of all age groups. Recent shifts in public awareness, increased screening and
recognition of symptoms and updated diagnostic criteria have led to an increase
in men diagnosed as hypogonadal, including middle-aged and older men who
previously would have been considered eugonadal. The increase in testosterone
replacement therapy (TRT) has paralleled an increase in advancements of treatment
options. Although current therapies are highly efficacious for many men, there
remains a need for newer therapies that are more cost-effective, preserve ease of
use and administration, mitigate undesirable effects and closely mimic
physiological levels of testosterone. AREAS COVERED: In this review, the authors
discuss current TRTs and therapies in development for the treatment of
hypogonadism. The focus is on therapies under Phase II investigation or those who
have recently completed Phase II study. EXPERT OPINION: With several new
therapies in development, the authors expect advancements in achieving treatment
benchmarks that meet the needs of the individual symptomatic hypogonadal male.
Increased public awareness of hypogonadism and TRT has led to a welcomed
expansion in the choice of TRT options. These include new delivery systems,
formulations, routes of administration and non-testosterone modalities.
PMID- 25113659
TI - A simple and sensitive fluorescence based biosensor for the determination of uric
acid using H2O2-sensitive quantum dots/dual enzymes.
AB - A novel optical detection system consisting of combination of uricase/HRP-CdS
quantum dots (QDs) for the determination of uric acid in urine sample is
described. The QDs was used as an indicator to reveal fluorescence property of
the system resulting from enzymatic reaction of uricase and HRP (horseradish
peroxidase), which is involved in oxidizing uric acid to allaintoin and hydrogen
peroxide. The hydrogen peroxide produced was able to quench the QDs fluorescence,
which was proportional to uric acid concentration. The system demonstrated
sufficient activity of uricase and HRP at a ratio of 5U:5U and pH 7.0. The
linearity of the system toward uric acid was in the concentration range of 125
1000 uM with detection limit of 125 uM.
PMID- 25113660
TI - Examining the link between adolescent brain development and risk taking from a
social-developmental perspective (reprinted).
AB - The adolescent age period is often characterized as a health paradox because it
is a time of extensive increases in physical and mental capabilities, yet overall
mortality/morbidity rates increase significantly from childhood to adolescence,
often due to preventable causes such as risk taking. Asynchrony in developmental
time courses between the affective/approach and cognitive control brain systems,
as well as the ongoing maturation of neural connectivity are thought to lead to
increased vulnerability for risk taking in adolescence. A critical analysis of
the frequency of risk taking behaviors, as well as mortality and morbidity rates
across the lifespan, however, challenges the hypothesis that the peak of risk
taking occurs in middle adolescence when the asynchrony between the different
developmental time courses of the affective/approach and cognitive control
systems is the largest. In fact, the highest levels of risk taking behaviors,
such as alcohol and drug use, often occur among emerging adults (e.g.,
university/college students), and highlight the role of the social context in
predicting risk taking behavior. Moreover, risk taking is not always unregulated
or impulsive. Future research should broaden the scope of risk taking to include
risks that are relevant to older adults, such as risky financial investing,
gambling, and marital infidelity. In addition, a lifespan perspective, with a
focus on how associations between neural systems and behavior are moderated by
context and trait-level characteristics, and which includes diverse samples
(e.g., divorced individuals), will help to address some important limitations in
the adolescent brain development and risk taking literature.
PMID- 25113662
TI - Mechanochemical preparation of nanocrystalline BaFCl doped with samarium in the
2+ oxidation state.
AB - We report a facile mechanochemical preparation method for nanocrystalline BaFCl
doped with samarium in the 2+ oxidation state by ball milling BaCl2, BaF2, and
SmI2 under a nitrogen atmosphere. The resulting phosphors were characterized by
powder X-ray diffraction; electron microscopy, X-ray photoelectron spectroscopy;
and photoluminescence, photoexcitation, cathodoluminescence, and diffuse
reflectance spectroscopy. This is the first report of a direct preparation method
of Sm(2+) doped alkaline earth fluorohalides at room temperature and points to a
significant potential for the preparation of a wide range of related X-ray
storage phosphors containing rare earth ions in divalent and trivalent cationic
states by mechanochemical methods.
PMID- 25113661
TI - Laparoscopic repair of posttraumatic diaphragmatic rupture. Report of three
cases.
AB - INTRODUCTION: Posttraumatic diaphragmatic rupture (PTDR) is a rare complication
of thoracoabdominal injuries. In the emergency phase, it is generally treated via
wide laparotomy. The laparoscopic approach is controversial and it is reserved
for the chronic type of PTDR. Herein we present three cases of laparoscopic
treatment of PTDR, one of which was conducted early after the injury.
PRESENTATION OF CASE: The patients' age was 42, 66 and 53 years and the time from
the injury until the operation 1 week, 2 months and 4 years, respectively. Hernia
involved the left hemidiaphragm in two patients and the right hemidiaphragm in
the second patient. Prolapsing viscera were the omentum/stomach/spleen, the small
intestine and the omentum/large bowel, respectively. The PTDR was diagnosed right
after the injury of the first patient but its treatment was postponed until the
fourth day of hospitalization because of severe respiratory distress due to
bilateral pneumothorax, flail chest and extended bilateral lung contusions. All
patients underwent laparoscopic operation and correction of the hernia with the
use of non-absorbable sutures or endoclips in two patients. There were no serious
intra- or postoperative complications and the patients were discharged 30, 5, 6
days after the operation. After a period of 1, 8 and 9 years, respectively the
patients remain without clinical evidence of recurrence. DISCUSSION: Trauma is
the major cause of acquired diaphragmatic hernias. CONCLUSION: Laparoscopy is an
attractive approach for the management of chronic PTDR. Moreover, it may offer
the benefits of minimally invasive surgery during the acute phase of injury in
highly selected patients.
PMID- 25113663
TI - Relighting behaviour among cigarette smokers seeking treatment: implications for
tobacco treatment and policy.
AB - AIMS: During the recent economic downturn, trends towards fewer cigarettes smoked
per day have emerged along with the practice of extinguishing and relighting
cigarettes. Few studies have characterised factors related to relighting
cigarettes and none have explored this behaviour in those seeking tobacco
treatment. This study describes treatment-seeking patients who relight cigarettes
and examines implications on tobacco policy and treatment. METHODS: Data were
collected from a cross-sectional sample of 496 patients at a specialty tobacco
treatment programme in New Jersey from 2010 to 2012. RESULTS: Forty-six per cent
of the sample reported relighting, and those subjects smoked significantly fewer
cigarettes per day (CPD), despite similar levels of dependence and exhaled carbon
monoxide (CO) values. In unadjusted analyses, significantly higher rates of
relighting were found among females, African-Americans, smokers who had a high
school diploma or less, and were unemployed, sick or disabled. Relighting was
more prevalent among smokers with higher markers of dependence, menthol smoking
and night smoking. In multivariate analyses, markers of dependence and economic
factors (employment and education) remained significant. CONCLUSIONS:
Characteristics linked to economic factors were related to increased relighting.
Implications for tobacco treatment include the impact on pharmacotherapy dosing
and counselling interventions. The tobacco control community needs to be aware of
this phenomenon. Collecting data on 'smoking sessions per day' might be a more
accurate depiction of smoking exposure than CPD.
PMID- 25113664
TI - Time to analgesia for care delivered by nurse practitioners in the emergency
department - a retrospective chart audit.
AB - OBJECTIVES: To evaluate quality of care delivered to patients presenting to the
emergency department (ED) with pain and managed by emergency nurse practitioners
by: 1 Evaluating time to analgesia from initial presentation 2 Evaluating time
from being seen to next analgesia 3 Measuring pain score documentation
BACKGROUND: The delivery of quality care in the emergency department (ED) is
emerging as one of the most important service indicators being measured by health
services. Emergency nurse practitioner services are designed to improve timely,
quality care for patients. One of the goals of quality emergency care is the
timely and effective delivery of analgesia for patients. Timely analgesia is an
important indicator of ED service performance. METHODS: A retrospective explicit
chart review of 128 consecutive patients with pain and managed by emergency nurse
practitioners was conducted. Data collected included demographics, presenting
complaint, pain scores, and time to first dose of analgesia. Patients were
identified from the ED patient information system (Cerner log) and data were
extracted from electronic medical records. RESULTS: Pain scores were documented
in 67 (52.3%; 95% CI: 43.3-61.2) patients. The median time to analgesia from
presentation was 60.5 (IQR 30-87) minutes, with 34 (26.6%; 95% CI: 19.1-35.1)
patients receiving analgesia within 30 minutes of presentation to hospital. There
were 22 (17.2%; 95% CI: 11.1-24.9) patients who received analgesia prior to
assessment by a nurse practitioner. Among patients who received analgesia after
assessment by a nurse practitioner, the median time to analgesia after assessment
was 25 (IQR 12-50) minutes, with 65 (61.3%; 95% CI: 51.4-70.6) patients receiving
analgesia within 30 minutes of assessment. CONCLUSIONS: The majority of patients
assessed by nurse practitioners received analgesia within 30 minutes after
assessment. However, opportunities for substantial improvement in such times
along with documentation of pain scores were identified and will be targeted in
future research.
PMID- 25113665
TI - A new method for modeling coalescent processes with recombination.
AB - BACKGROUND: Recombination plays an important role in the maintenance of genetic
diversity in many types of organisms, especially diploid eukaryotes.
Recombination can be studied and used to map diseases. However, recombination
adds a great deal of complexity to the genetic information. This renders
estimation of evolutionary parameters more difficult. After the coalescent
process was formulated, models capable of describing recombination using graphs,
such as ancestral recombination graphs (ARG) were also developed. There are two
typical models based on which to simulate ARG: back-in-time model such as ms and
spatial model including Wiuf&Hein's, SMC, SMC', and MaCS. RESULTS: In this study,
a new method of modeling coalescence with recombination, Spatial Coalescent
simulator (SC), was developed, which considerably improved the algorithm
described by Wiuf and Hein. The present algorithm constructs ARG spatially along
the sequence, but it does not produce any redundant branches which are inevitable
in Wiuf and Hein's algorithm. Interestingly, the distribution of ARG generated by
the present new algorithm is identical to that generated by a typical back-in
time model adopted by ms, an algorithm commonly used to model coalescence. It is
here demonstrated that the existing approximate methods such as the sequentially
Markov coalescent (SMC), a related method called SMC', and Markovian coalescent
simulator (MaCS) can be viewed as special cases of the present method. Using
simulation analysis, the time to the most common ancestor (TMRCA) in the local
trees of ARGs generated by the present algorithm was found to be closer to that
produced by ms than time produced by MaCS. Sample-consistent ARGs can be
generated using the present method. This may significantly reduce the
computational burden. CONCLUSION: In summary, the present method and algorithm
may facilitate the estimation and description of recombination in population
genomics and evolutionary biology.
PMID- 25113666
TI - The palmar approach for PIP-arthroplasty according to Simmen: results after 8
years follow-up.
AB - BACKGROUND: Alloarthroplasty of the proximal interphalangeal joint is indicated
for patients with osteoarthritis, an inflammatory disease of the joint. According
to the current literature, implants made of silicone are not inferior to newer
implants and the complications are well known. Therefore, focus should be shifted
to the operative approach to improve the results. METHODS: Eleven silicone
arthroplasties in 7 patients with arthritis and 35 silicone arthroplasties in 23
patients with osteoarthritis were reviewed after 15.6 months and after 105.3
months. All implants were inserted using the palmar approach according to Simmen.
We compared the pre- and postoperative arc of motion, pain, and strength, and
present postoperative complications and satisfaction. RESULTS: Patients with
arthritis showed a gain in range of motion of 36 degrees and patients with
osteoarthritis of 39 degrees . No implant failure occurred, and one revision was
performed,. Average extension lag over all operated joints of patients was 2.8
degrees . No swan-neck deformity or extensor tendon adhesion was observed. There
was no significant difference in the postoperative results between patients with
osteoarthritis and arthritis or between first and second follow-up. CONCLUSION:
Silicone arthroplasty restores the functionality of proximal interphalangeal
joints in patients with osteoarthritis and inflammatory joint disease. Using a
palmar approach, the surgeon can reach palmar and dorsal osteophytes. The
extensor mechanism stays intact reducing the risk for extensor lag and other
complications compared to the dorsal approach. The results do not change
significantly between 1 and 8 years postoperatively.
PMID- 25113667
TI - Bone substitute first or screws first? A biomechanical comparison of two
operative techniques for tibial-head depression fractures.
AB - BACKGROUND: The aim of this study was to investigate a drillable and injectable
bone substitute (calcium phosphate cement) and the operative technique enabled by
the drillable option in a new biomechanical fracture model for tibial depression
fractures in synthetic bones. MATERIALS AND METHODS: Lateral depression fractures
of the tibial plateau (AO 41-B2, Schatzker III) were created in a biomechanical
fracture model in three different synthetic bones (Sawbone 3401, Synbone
1110/1116). Reproducible fractures were generated employing Synbone 1110, which
exhibited a comparable strength to human osteoporotic bones and was used for the
further experiments. After reduction of the fractures, the stabilization was
performed with two different operative techniques. In group 1, first an
osteosynthesis with four screws was performed and then the metaphyseal defect was
filled up with calcium phosphate cement (Norian drillable). In group 2, initially
the filling up with Norian drillable was done enabling a complete filling of the
defect, followed by placing of the screws. Displacement under cyclic loading with
250 N for 3,000 cycles, stiffness, and maximum load in load-to-failure tests were
determined. RESULTS: A comparison of the two operative techniques of
stabilization showed a distinctly lower displacement and higher stiffness for
group 2 when the defect was filled up first. For the maximum load, no significant
differences could be demonstrated. CONCLUSIONS: A complete filling of the defect
by first applying the calcium phosphate cement significantly reduces the
secondary loss of reduction of the depression fracture fragment under cyclic
loading with a clinically relevant partial weight bearing. The beneficial effects
of drillable calcium phosphate cement may also be transferable to defects other
than tibial-head depression fractures.
PMID- 25113669
TI - Alkene carboboration enabled by synergistic catalysis.
AB - A synergistic Pd/Cu system for the coupling of alkenes, (Bpin)2 (pin =
pinacolate), and aryl/vinyl bromides is disclosed. This method allows for the
catalytic generation of secondary Csp(3)-Cu nucleophiles in situ and subsequent
Pd-catalyzed cross-coupling.
PMID- 25113668
TI - Metabotropic glutamate receptor 1 recycles to the cell surface in protein
phosphatase 2A-dependent manner in non-neuronal and neuronal cell lines.
AB - Trafficking of G protein-coupled receptors plays a crucial role in controlling
the precise signalling of the receptor as well as its proper regulation.
Metabotropic glutamate receptor 1 (mGluR1), a G protein-coupled receptor, is a
member of the group I mGluR family. mGluR1 plays a critical role in neuronal
circuit formation and also in multiple types of synaptic plasticity. This
receptor has also been reported to be involved in various neuropsychiatric
diseases. Other than the central nervous system, mGluR1 plays crucial roles in
various non-neuronal cells like hepatocytes, skin cells, etc. Although it has
been reported that mGluR1 gets endocytosed on ligand application, the events
after the internalization of the receptor has not been studied. We show here that
mGluR1 internalizes on ligand application. Subsequent to endocytosis, majority of
the receptors localize at the recycling compartment and no significant presence
of the receptor was noticed in the lysosome. Furthermore, mGluR1 returned to the
cell membrane subsequent to ligand-mediated internalization. We also show here
that the recycling of mGluR1 is dependent on the activity of protein phosphatase
2A. Thus, our data suggest that the ligand-mediated internalized receptors
recycle back to the cell surface in protein phosphatase 2A-dependent manner.
PMID- 25113671
TI - Investigation of phase diagrams and physical stability of drug-polymer solid
dispersions.
AB - Solid dispersion technology has been widely explored to improve the solubility
and bioavailability of poorly water-soluble compounds. One of the critical
drawbacks associated with this technology is the lack of physical stability, i.e.
the solid dispersion would undergo recrystallization or phase separation thus
limiting a product's shelf life. In the current study, the melting point
depression method was utilized to construct a complete phase diagram for
felodipine (FEL)-Soluplus(r) (SOL) and ketoconazole (KTZ)-Soluplus(r) (SOL)
binary systems, respectively, based on the Flory-Huggins theory. The miscibility
or solubility of the two compounds in SOL was also determined. The Flory-Huggins
interaction parameter chi values of both systems were calculated as positive at
room temperature (25 degrees C), indicating either compound was miscible with
SOL. In addition, the glass transition temperatures of both solid dispersion
systems were theoretically predicted using three empirical equations and compared
with the practical values. Furthermore, the FEL-SOL solid dispersions were
subjected to accelerated stability studies for up to 3 months.
PMID- 25113672
TI - Complete genome sequence analysis of goatpox virus isolated from China shows high
variation.
AB - Goatpox virus (GTPV), a member of the Capripoxvirus genus of the Poxviridae
family, is the causative agent of variolo caprina (goatpox). GTPV can cause
significant economic losses of domestic ruminants in endemic regions and can
threaten breeding stocks. In this study, we report on the compilation of the
complete genomic sequence of an isolated GTPV field strain FZ (GTPV_FZ). The
150,194bp GTPV genome consists of a central coding region bounded by two
identical 2301bp inverted terminal repeats and contains 151 putative genes.
Comparative genomic analysis reveals the apparent genetic relationships among
Capripoxviruses are close, but sufficient genomic variants in the field isolate
strain FZ have been identified to distinguish it from other GTPV strains and
other Capripoxvirus species. Phylogenetic analysis based on the p32 and complete
GTPV genome can be used to differentiate SPPVs, GTPVs and LSDVs. These data may
contribute to the epidemiological study of the Chinese capripoxvirus and help to
develop more specific detection methods to distinguish GTPVs, SPPVs and LSDVs.
PMID- 25113670
TI - Intrathecal delivery of mesenchymal stromal cells protects the structure of
altered perineuronal nets in SOD1 rats and amends the course of ALS.
AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder
resulting in a lethal outcome. We studied changes in ventral horn perineuronal
nets (PNNs) of superoxide dismutase 1 (SOD1) rats during the normal disease
course and after the intrathecal application (5 * 10(5) cells) of human bone
marrow mesenchymal stromal cells (MSCs) postsymptom manifestation. We found that
MSCs ameliorated disease progression, significantly improved motor activity, and
prolonged survival. For the first time, we report that SOD1 rats have an abnormal
disorganized PNN structure around the spinal motoneurons and give different
expression profiles of chondroitin sulfate proteoglycans (CSPGs), such as
versican, aggrecan, and phosphacan, but not link protein-1. Additionally, SOD1
rats had different profiles for CSPG gene expression (Versican, Hapln1, Neurocan,
and Tenascin-R), whereas Aggrecan and Brevican profiles remained unchanged. The
application of MSCs preserved PNN structure, accompanied by better survival of
motorneurons. We measured the concentration of cytokines (IL-1alpha, MCP-1, TNF
alpha, GM-CSF, IL-4, and IFN-gamma) in the rats' cerebrospinal fluid and found
significantly higher concentrations of IL-1alpha and MCP-1. Our results show that
PNN and cytokine homeostasis are altered in the SOD1 rat model of ALS. These
changes could potentially serve as biological markers for the diagnosis,
assessment of treatment efficacy, and prognosis of ALS. We also show that the
administration of human MSCs is a safe procedure that delays the loss of motor
function and increases the overall survival of symptomatic ALS animals, by
remodeling the recipients' pattern of gene expression and having neuroprotective
and immunomodulatory effects.
PMID- 25113674
TI - Six new species, complementary descriptions and new records from the Neotropical
Region of the spider genus Dipoena (Araneae: Theridiidae).
AB - The theridiid genus Dipoena Thorell, 1869 is distributed worldwide. Dipoena are
recognized by male with carapace often high, cylindrical, with grooves or
depression on dorsum; carapace of female rarely modified, sometimes high. In this
paper six new species of Dipoena are described from Brazil, one from the state of
Mato Grosso do Sul: Dipoena bonitensis new species, three from Sao Paulo: Dipoena
cidae new species, Dipoena ericae new species and Dipoena
santaritadopassaquatrensis new species and two from Parana: Dipoena guaraquecaba
new species and Dipoena fozdoiguacuensis new species, all based on males and
females. The males of Dipoena pusilla (Keyserling, 1886); D. peruensis Levi,
1963; D. olivenca Levi, 1963 and D. esra Levi, 1963 and the female of Dipoena
niteroi Levi, 1963 are here described and illustrated for the first time. New
records from Brazil include Dipoena augara Levi, 1963; D. bryantae Chickering,
1943; D. duodecimpunctata Chickering, 1943; D. isthmia Chickering, 1943; D.
kuyuwini Levi, 1963; D. mendoza Levi, 1967; D. puertoricensis Levi, 1963; D. tiro
Levi, 1963 and D. trinidensis Levi, 1963; and new records from Bolivia include
Dipoena atlantica Chickering, 1943, D. cornuta Chickering, 1943 and D. kuyuwini.
New distribution records within Brazil are presented for Dipoena cordiformis
Keyserling, 1886; D. hortoni Chickering, 1943; D. ira Levi, 1963; D. militaris
Chickering, 1943; D. obscura Keyserling, 1891; D. pumicata (Keyserling, 1886); D.
santacatarinae Levi, 1963; D. tingo Levi, 1963 and D. variabilis (Keyserling,
1886).
PMID- 25113673
TI - Pheno- and genotyping of Brucella abortus biovar 5 isolated from a water buffalo
(Bubalus bubalis) fetus: First case reported in the Americas.
AB - An isolate of Brucella spp. from an aborted water buffalo (Bubalus bubalis) fetus
was characterized based on its pheno- and genotype. The phenotype was defined by
carbon dioxide requirement, hydrogen sulfide production, sensitivity to thionin
and basic fuchsin and agglutination with Brucella A and M monospecific antisera.
The genotype was based on the amplification of the following genes: bcsp31,
omp2ab, and eri and the species-specific localization of the insertion sequence
IS711 in the Brucella chromosome via B. abortus-B. melitensis-B. ovis-B. suis
(AMOS)-PCR. Unexpectedly, the isolate showed a phenotype different from B.
abortus bv 1, the most prevalent strain in cattle in Argentina, and from vaccine
strain 19, currently used in bovines and water buffaloes. Genotyping supported
the phenotypic results, as the analysis of the omp2ab gene sequence showed an
identical pattern to either B. abortus bv 5 or B. melitensis. Finally, the AMOS
PCR generated a 1700-bp fragment from the isolate, different than those amplified
from B. abortus bv 1 (498bp) and B. melitensis (731bp), confirming the presence
of B. abortus bv 5. The OIE/FAO Reference Laboratory for Brucellosis confirmed
this typing. This is the first report of B. abortus bv 5 from a water buffalo in
the Americas.
PMID- 25113675
TI - A taxonomic revision of South African Sharphydrus, with the description of two
new species (Coleoptera: Dytiscidae: Bidessini).
AB - Sharphydrus Omer-Cooper, 1958 is one of two endemic bidessine genera currently
recognised from South Africa. Here Sharphydrus brincki sp. nov. and Sharphydrus
kamiesbergensis sp. nov. are described from the Cederberg and Gydopas areas of
the Western Cape, and the high Kamiesberg of the Northern Cape respectively,
doubling the known species of this genus. It is shown that S. brincki sp. nov.
has been included under S. capensis (Omer-Cooper, 1955) in the past, but that
these are quite distinct taxa, differing in the extent of their elytral keels and
male genitalia. Sharphydrus species are inhabitants of pools in seasonally
fluctuating rivers, the new species described here occurring in areas which are
somewhat transitional between fynbos and karoo biomes. An updated key is
presented to Sharphydrus species, together with data on the distribution and
ecology of known species, and a discussion of the status of the genus within the
Bidessini.
PMID- 25113676
TI - Psorodonotus venosus group (Orthoptera, Tettigoniidae; Tettigoniinae): geometric
morphometry revealed two new species in the group.
AB - Psorodonotus (Orthoptera, Tettigoniidae) includes 11 species distributed in
Caucasus, Anatolia and Balkans. Although its present taxonomy is problematic,
mainly three species groups can be distinguished; (i) The Specularis Group, (ii)
The Caucasicus Group and (iii) The Venosus Group. Our recent studies on the genus
have revealed presence of two new species in the last species group. Morphology
of the species group studied both qualitatively and quantitatively using linear
metric data of pronotum, tegmina and hind femur, and geometric data of male cerci
and ovipositor. Morphological data were accompanied by data obtained from male
calling song. Morphological and song data were produced from six different
populations from North and Eastern part of Turkey: (1) Hakkari, (2) Tendurek, (3)
Giresun, (4) Artvin, (5) Kars and (6) Agri. Qualitative and quantitative
morphology, either linear-metric or geometric, suggest last three population as
members of the same unit, but each of other three as different units. Song data
are also largely in support of the morphological results. Necessary illustrations
were provided to document results visually. Following conclusions were made: (1)
the Artvin, Kars and Agri populations represent typical P. venosus and the
Giresun population P. rugulosus, (2) each of the Hakkari and Tendurek populations
represents a new species and P. hakkari sp. n. and P. tendurek sp. n. described
by comparing with other members of P. venosus group, (3) P. rugulosus, P. hakkari
sp. n. and P. tendurek sp. n. differ from P. venosus mainly by the longer cerci
(extend to or beyond end of abdomen) and indistinct tubercles on surface of
pronotal disc in female. P. rugulosus and P. tendurek sp. n. are also similar by
sharing presence of two loud elements in a syllable (one in P. venosus, song of
P. hakkari sp. n. is not available). But, similarities in phenotype are in
conflict with relationships suggested by genetic data.
PMID- 25113677
TI - Revision of the genus Alkindus Distant (Hemiptera: Heteroptera: Thyreocoridae:
Corimelaeninae).
AB - The neotropical genus Alkindus Distant is revised based on morphological
characters (general morphology, including the external scent efferent system and
leg structures, and external genital morphology). The male of Alkindus
crassicosta Horvath is here described for the first time. Illustrations, an
adapted key to species, and a compiled list of plants associated with both
species are provided. Distribution records are expanded to include Guatemala and
Brazil (Roraima) for Alkindus atratus Distant and Brazil (Santa Catarina) for A.
crassicosta.
PMID- 25113678
TI - Two new species of Gaeolaelaps (Acari: Laelapidae) from Iran.
AB - This paper reports on two new species of mites of the genus Gaeolaelaps in soil
from Iran, G. farajii sp. nov., and G. orbiculatus sp. nov.. A key to the species
of Gaeolaelaps with short peritremes is presented.
PMID- 25113679
TI - The red-listed species Thamnurgus rossicus in East Europe is a synonym of the
rare Central European species, T. petzi (Curculionidae: Scolytinae).
AB - The taxonomic status of Thamnurgus rossicus was evaluated with respect to the
morphologically similar T. petzi using genetic markers. Nucleotide data from the
mitochondrial COI gene revealed 2.4% variation between the European Alps and
Russian steppe populations. The two nuclear DNA markers CAD and EF1a were
identical across populations. In view of their similar morphology, genetic
composition, and the partial overlap in host plant preferences (Ranunculaceae:
Aconitum and Delphinium), T. rossicus is placed in synonymy with T. petzi.
PMID- 25113680
TI - A new species of the genus Thoracochirus Bernhauer (Coleoptera: Staphylinidae:
Osoriinae) from Yunnan, China.
AB - Thoracochirus yunxianius sp. nov. is described from Yunnan, China. Color images
of the habitus and aedeagus of the new species are included. A key to the genus
Thoracochirus of mainland China species is provided.
PMID- 25113681
TI - A new species of Labiobaetis Novikova & Kluge, 1987 (Ephemeroptera: Baetidae)
from Washington, USA.
AB - Labiobaetis sonajuventus n.sp. is described from nymphs collected in a tributary
of the Okanogan River in north-central Washington, USA. The new species is
distinguished from North American congeners by the well-developed keel between
the bases of the antennae, the concave lateral margin of labial palp segment 2,
the apically expanded submarginal setae on the labrum, and its western Nearctic
distribution.
PMID- 25113683
TI - Adults and larvae of two Leucochrysa (Leucochrysa) species (Neuroptera:
Chrysopidae): descriptions, biological notes, and relationships.
AB - This taxonomic study includes: (i) a redescription of Leucochrysa (Leucochrysa)
nigrilabris (Banks) (? and ?), based on the type specimen and new material and
(ii) images of the Leucochrysa (L.) insularis (Walker) type, adult color
polymorphism, and genital characters (? and ?). For both species, it provides:
(iii) descriptions of the larvae, (iv) biological notes, and (v) geographic
records. Using the above information, we compare the two species with each other
and with other Leucochrysa (Leucochrysa) species that purportedly are closely
related. We conclude: First, the larval features of L. (L.) nigrilabris and L.
(L.) insularis coincide with those previously described as characteristic of the
genus Leucochrysa and its subgenus Leucochrysa. Second, based on their genitalia
(? and ?), larval morphology, and biology (e.g., deposition of eggs in clusters),
the two species are distinct, but very closely related. And, third, L. (L.)
nigrilabris and L. (L.) insularis share several characteristics with the
Leucochrysa (L.) "varia-like" species; these include similar adult color
polymorphisms and aspects of their larval morphology. However, their genitalia (?
and ?) differ significantly from those of the described L. (L.) "varia-like"
species, and thus we consider the two sets of species to be distinct.
PMID- 25113684
TI - A new genus and species of Discozerconidae (Acari: Mesostigmata) from carabid
beetles (Coleoptera: Carabidae) in New Zealand .
AB - Berzercon ferdinandi gen. nov., sp. nov. (Acari: Mesostigmata: Discozerconidae)
is described from carabid beetles in New Zealand. As in all Discozerconidae,
Berzercon has large ventrally-directed opisthogastric suckers. However it is
distinctive in its long marginal setae, tripartite gnathotectum, fused palp tibia
and tarsus, the female's large dome-shaped genital shield and the male's highly
modified hypostomal seta h1. This new species also represents the first
Heterozerconina from an insect host.
PMID- 25113685
TI - Taxonomic review of the genus Rhinoncomimus (Coleoptera: Curculionidae:
Ceutorhynchinae) with description of a new species from Yunnan, China.
AB - The genus Rhinoncomimus Wagner, 1940 includes seven species from Eastern Asia.
One new species, Rh. continuus sp. nov. from Yunnan, China, is described. Habitus
photos, illustrations and descriptions of all species except Rh. rubripes
Korotyaev, 2006 (a possible junior synonym of R. niger Chujo and Morimoto, 1959)
are provided in detail, as well as key to species and distribution maps. In
addition, the host plant of the type species Rh. klapperichi Wagner, 1940,
Polygonum hydropiper L. (Polygonaceae) is newly recorded.
PMID- 25113686
TI - Paratylenchus shenzhenensis n. sp. (Nematoda: Paratylenchinae) from the
rhizosphere soil of Anthurium andraeanum in China.
AB - Paratylenchus shenzhenensis n. sp. was collected from the rhizosphere soil of
Anthurium andraeanum in Shenzhen, Guangdong Province, China. The new species is
characterized by having a female with a small body (249-302 MUm), well developed
stylet (17-21 MUm), rounded head with four submedian lobes and lip-region with a
slight depression at the oral area, small post-vulval uterine sac with a few
vestigial cells; male with body dorsally curved behind the cloacal opening,
stylet absent, pharynx degenerate, prominent penial sheath; and juveniles with a
stylet. It is morphologically similar to P. minutus. The internal transcribed
spacer sequences of ribosomal DNA (ITS-rDNA) of the new species only have 72-73%
identity with P. minutus, confirming its status as a separate species. The D2/D3
region of 28S ribosomal DNA (28S rDNA) and 18S small subunit ribosomal DNA (18S
rDNA) from P. shenzhenensis n. sp. were also amplified and sequenced in this
study.
PMID- 25113687
TI - Two new species of the genus Cicadatra Kolenati (Hemiptera: Cicadidae) from
Pakistan.
AB - Two new species of the genus Cicadatra Kolenati, C. ashrafi sp.n. and C.
tandojamensis sp.n. are described from Pakistan. Male genitalia, timbals and
opercula are described and illustrated as important diagnostic characters. Host
affinity for one species is also provided. A key to the known species of
Pakistani Cicadatra is also given.
PMID- 25113688
TI - The female of Heteropoda schwalbachorum Jager, 2008 (Araneae: Sparassidae).
PMID- 25113690
TI - On the Australian linyphiid spider Alaxchelicera ordinaria Butler, 1932
(Araneae).
PMID- 25113689
TI - A simple device to collect, store and study samples of two-dimensional spider
webs.
PMID- 25113691
TI - The use of the prefix Pan- and other problems in zoological family-series
nomenclature.
PMID- 25113692
TI - On the identities of Barbus mussullah Sykes and Cyprinus curmuca Hamilton with
notes on the status of Gobio canarensis Jerdon (Teleostei: Cyprinidae).
AB - The identity and generic placement of Barbus mussullah Sykes, the type species of
Hypselobarbus Bleeker, have for long been unclear, variously having been
considered a synonym of Cyprinus curmuca Hamilton or a species of Tor Gray or
Gonoproktopterus Bleeker. Here, through a re-examination of the original
descriptions and the examination of specimens from western peninsular India, we
redescribe H. mussullah and show that Hypselobarbus is a valid genus, of which
Gonoproktopertus is a junior synonym. Hypselobarbus mussullah is distinguished
from all other species of Hypselobarbus by possessing both rostral and maxillary
barbels; having the last simple dorsal-fin ray weak and smooth; the lateral line
complete, with 41 +1 pored scales; 9/1/4 scales in transverse line between
origins of dorsal and pelvic fins; and 51/2 scales between lateral line and anal
fin origin. Species of Hypselobarbus are distinguished from other genera of
Cyprinidae by possessing long, branched gill rakers and the anal fin distally
rounded in adults. Hypselobarbus canarensis was found to be a valid species and
H. kurali is considered its synonym. Hypselobarbus canarensis can be
distinguished from all congeners by possessing both rostral and maxillary
barbels; having the last simple dorsal-fin ray weak and smooth; the lateral line
complete, with 40-42+1 pored scales; 1/27-1/28/1/31/2 scales in transverse line
from dorsal-fin origin to pelvic-fin origin; 41/2 scales between lateral line and
anal-fin origin. Hypselobarbus kolus is considered a synonym of H. curmuca, which
is redescribed: it is distinguished from all congeners by possessing maxillary
barbels only; the last simple dorsal-fin ray weak and smooth; 41-43+1 lateral
line scales; 9-10/1/41/2-5 scales in transverse line between origins of dorsal
and pelvic fins; and 51/2-6 scales between lateral line and anal-fin origin.
PMID- 25113693
TI - Acanthoplesiops cappuccino, a new species of acanthoclinine fish from the Red Sea
(Teleostei: Plesiopidae) .
AB - Acanthoplesiops cappuccino is described from the 16.4 mm SL holotype collected
from Jeddah, Saudi Arabia, Red Sea. The following combination of characters
distinguishes it from congeners: dorsal-fin rays XVIII,4; anal-fin rays VII,4;
pectoral-fin rays 18; caudal fin not connected to last rays of dorsal and anal
fins by membrane; and caudal peduncle with a pale yellowish brown bar, which
extends broadly on to caudal fin. An underwater photo of the anaesthetised
holotype is provided, as well as one of the freshly dead holotype and only known
specimen of the similar species A. naka. Tables summarizing diagnostic characters
of the six known species of Acanthoplesiops are included. congeners by possessing
both rostral and maxillary barbels; having the last simple dorsal-fin ray weak
and smooth; the lateral line complete, with 40-42+1 pored scales; 1/27
1/28/1/31/2 scales in transverse line from dorsal-fin origin to pelvic-fin
origin; 41/2 scales between lateral line and anal-fin origin. Hypselobarbus kolus
is considered a synonym of H. curmuca, which is redescribed: it is distinguished
from all congeners by possessing maxillary barbels only; the last simple dorsal
fin ray weak and smooth; 41-43+1 lateral-line scales; 9-10/1/41/2-5 scales in
transverse line between origins of dorsal and pelvic fins; and 51/2-6 scales
between lateral line and anal-fin origin.
PMID- 25113694
TI - Cambarus (C.) hatfieldi, a new species of crayfish (Decapoda:Cambaridae) from the
Tug Fork River Basin of Kentucky, Virginia and West Virginia, USA.
AB - Cambarus (Cambarus) hatfieldi is a stream-dwelling crayfish that appears to be
endemic to the Tug Fork River system of West Virginia, Virginia, and Kentucky.
Within this region, it is prevalent in all major tributaries in the basin as well
as the Tug Fork River's mainstem. The new species is morphologically most similar
to Cambarus sciotensis and Cambarus angularis. It can be differentiated from C.
sciotensis by its squamous, subtrinagular chelae compared to the elongate
triangular chelae of C. sciotensis; its shorter palm length/palm depth ratio
(1.9) compared to C. sciotensis (2.3); and a smaller areola length/total carapace
length ratio (30.4% vs.36.5% respectively). Cambarus hatfieldi can be
differentiated from C. angularis by its smaller areola length/total carapace
length ratio (30.4% vs. 36.7% respectively); a smaller rostrum width/rostral
length ratio (59.4% vs. 67.2% respectively); its rounded abdominal pleura as
compared to the subtruncated pleura of C. angularis; the length of the central
projection and mesial process of C. hatfieldi which both extend to the margin of
the gonopod shaft or slightly beyond the margin compared to the central
projection of C. sciotensis and C. angularis where both extend well beyond the
margin of the gonopod shaft.
PMID- 25113695
TI - An update of the blow flies (Diptera: Calliphoridae) of the Galapagos Islands,
and first record of Chrysomya rufifacies (Macquart) from mainland Ecuador.
AB - Seven species of Calliphoridae are reported from the Galapagos Islands, Ecuador:
Lucilia pionia (Walker), L. setosa (James), L. deceptor (Curran), L. eximia
(Wiedemann), Cochliomyia macellaria (Fabricius), Chrysomya albiceps (Wiedemann),
and Chrysomya megacephala (Fabricius). Lucilia eximia is newly recorded from the
islands. Lucilia sp. near pionia is recorded from the island of Espanola. The
distribution and collection records of these species are discussed and listed,
and a key to their identification is provided. Chrysomya rufifacies (Macquart) is
reported for the first time from mainland Ecuador and the identification of this
species is outlined.
PMID- 25113696
TI - Terataki, a new genus of Staphylinini (Coleoptera: Staphylinidae: Staphylininae)
from South America.
AB - A new genus of Xanthopygina is described here as Terataki gen. n. and includes
the following species: Te. badiipennis comb. n., Te. caterinoi sp. n., Te.
erithracus comb. n. and Te. liliputanum comb. n. Lectotypes are designated for
Creophilus badiipennis Nordmann, C. chloris Nordmann, C. erithracus Nordmann and
Polyphematiana liliputana Bernhauer. Creophilus chloris is shown to be a junior
synonym of C. erithracus and Trigonopselaphus nobilis Wendeler a junior synonym
of C. badiipennis. A key and illustrations of structural features are provided
for the identification of specimens.
PMID- 25113697
TI - The salmon, the lungfish (or the coelacanth) and the cow: a revival?
PMID- 25113698
TI - On three monotypic nursery web spider genera from Madagascar with first
description of the male of Tallonia picta Simon, 1889 and redescription of the
type-species of Paracladycnis Blandin, 1979 and Thalassiopsis Roewer, 1955
(Araneae: Lycosoidea: Pisauridae).
PMID- 25113699
TI - The Neotropical chloropine genus Ischnochlorops Paganelli 2002 (Diptera:
Chloropidae), with the description of a new species.
AB - A new species is described for the Neotropical genus Ischnochlorops Paganelli
(Diptera: Chloropidae), so far known only from the type-species, I. trilineatus
Paganelli. The type-species is redescribed based on an additional male from the
State of Parana. A new species, I. lefevrei sp. nov., from Campos do Jordao,
State of Sao Paulo, Brazil, is described. An emended diagnosis is proposed for
Ischnochlorops and a key to the species is provided. Photographs of the habitus,
head, and wing of both species are provided, as well as drawings of the male
terminalia.
PMID- 25113700
TI - A new genus and species of Vartini (Hemiptera: Cicadellidae: Deltocephalinae)
from Africa.
AB - A new genus and species of the leafhopper tribe Vartini are described. Afrovarta
angelae gen. & sp. nov. are described based on specimens from Ghana, Cameroon,
and Gabon.
PMID- 25113701
TI - Morphological and acoustic characterization of Proceratophrys goyana
(Lissamphibia: Anura: Odontophrynidae), with the description of a sympatric and
related new species.
AB - Proceratophrys goyana was until recently the only species of the genus described
from central Brazil. In this paper we characterize the adult morphology and
advertisement call of this species, based on data collected at its type-locality
(Chapada dos Veadeiros, Goias, Brazil). These new data allowed us to recognize a
new species of Proceratophrys, sympatric to P. goyana, which is described herein.
Proceratophrys goyana is mainly characterized by the male SVL = 38.8-46.5 mm; a
well-developed and continuous pair of dorsal sagittal ridges; upper eyelids
triangular; developed frontoparietal crests, delimiting a shallow depression
between them; overall color pattern browned, with the symmetrical dorsal ridges
bordered laterally by dark brown undulations. Proceratophrys rotundipalpebra sp.
nov. is characterized by the male SVL = 30.4-39.3 mm; the pair of symmetrical
dorsal ridges well-developed anteriorly and somewhat interrupted in the sacral
region; upper eyelids short and rounded; frontoparietal crests not well
developed; overall color pattern stained by 3-4 tonalities of gray, without a
clear background color. The advertisement calls of both species are emitted in a
multi-note pattern, each note pulsed, the first and last notes differing from
each other and from those amidst the call in temporal features. The description
of this new species is another example of the underestimated diversity of
Proceratophrys in the Cerrado of central Brazil.
PMID- 25113702
TI - Three new species of Proceratophrys Miranda-Ribeiro 1920 from Brazilian Cerrado
(Anura, Odontophrynidae).
AB - Based on the analyses of specimens collected at several areas in the Cerrado
domain from Central Brazil and others housed in scientific collections and on
specimens collected at the type-locality, herein we describe three new species
belonging to the P. cristiceps group: Proceratophrys bagnoi sp. nov., from UHE
Serra da Mesa power plant (13 degrees 49'47.5"S, 48 degrees 19'17"W; 570 m
a.s.l.; WGS84 datum), Municipality of Minacu, State of Goias; Proceratophrys
branti sp. nov., from Jalapao, Municipality of Mateiros (05o15'25"S,
48o12'00"W; 109 m a.s.l.; WGS84 datum), State of Tocantins; and
Proceratophrys dibernardoi sp. nov., Municipality of Mineiros
(17o33'52"S, 52o33'20"W; 803 m a.s.l.; WGS84 datum), State
of Goias. The diversity of Proceratophrys in Brazilian Cerrado is still
underscored and several species will be described in the following years.
PMID- 25113703
TI - Ultrastructure and morphometry of eggs of Triatoma rubrovaria (Blanchard, 1843),
Triatoma carcavalloi Juberg, Rocha & Lent, 1998 and Triatoma circummaculata
(Stal, 1859) (Hemiptera-Reduviidae-Triatominae).
AB - This study analyzed the body and the operculum of eggs of Triatoma rubrovaria, T.
carcavalloi and T. circummaculata, considered sylvatic species that live in
sympatry.Triatoma rubrovaria is currently considered the most important vector of
Trypanosoma cruzi in the rural areas of the state of Rio Grande do Sul, followed
by T.circummaculata. Significant differences other than morphometry have been
observed in the egg structures of the three species using traditional microscopy
and scanning electron microscopy. Triatoma circummaculata eggs are smaller than
those of T.rubrovaria and T. carcavalloi. The average number of perforations in
corionic cells in the egg body is higher for the T. rubrovaria. The average
number of perforations in the operculum cell is higher in T. circummaculata. This
is the first morpho-structural description of T. carcavalloi eggs. These results
widen the concept of these three species and create new subsidies for the
entomological monitoring in areas in which these vectors may infest human living
quarters.
PMID- 25113704
TI - Two new species of Aaptos (Demospongiae, Hadromerida) from Brazil (western
Atlantic).
AB - Twenty-one species of Aaptos Gray, 1867 are known world-wide, of which only three
were reported from Brazil. Two new species of this genus are here described from
the Brazilian coast (Potiguar Basin, Northeastern Brazil): A. hajdui sp. nov. and
A. potiguarensis sp. nov. Both possess only one category of strongyloxeas and one
of styles, although both with wide size variation, suggesting that the diagnosis
of the genus should be revised. Previous Brazilian records of A. aaptos have
their status re-evaluated here, and only three species of the genus can be
considered valid in Brazil: A. glutinans, A. hajdui sp. nov. and A. potiguarensis
sp. nov.
PMID- 25113705
TI - First zoeal stage of the partner shrimp Periclimenes paivai Chace, with remarks
on the genus Periclimenes O.G. Costa (Caridea, Palaemonidae.
AB - The morphology of the first zoeal stage of Periclimenes paivai Chace is described
and illustrated for the first time. Larvae were obtained from three females with
embryos, caught in the type locality (Cananeia, Sao Paulo state, Brazil). The
morphological characters are detailed and compared with all previous descriptions
of larvae in the genus (P. amethysteus, P. brevicarpalis, P. diversipes, P.
pandionis, P. sagittifer and P. soror). The zoeae I of Periclimenes species are
very similar, but P. paivai can be separated from the other six species by means
of five characteristics: 8 plumose setae on the inner margin of the antennal
scale, one spine on the endopod of the maxillule, one cuspidate seta on the basal
endite of the maxilulle, one plumose seta on the single coxal endite of the
maxilla, and one plumose seta on the endopod of the maxilla. Remarks from a
comparative analysis of available descriptions of the genus are furnished.
PMID- 25113706
TI - Cliona tumula sp. nov., a conspicuous, massive Symbiodinium-bearing clionaid from
the lower Florida Keys (USA)(Demospongiae: Hadromerida: Clionaidae).
AB - Cliona tumula sp. nov. is described from the Florida Keys, Florida, USA. The new
species is compared to representative Cliona spp. from the Caribbean and Indo
Pacific. Cliona tumula sp. nov. is a massive, mound-shaped zooxanthellate
clionaid with a central, apical cluster of numerous oscula, slender tylostyles
with variable heads and abundant, delicate spirasters with compound spines that
can be concentrated at the ends, which in this species can appear as mushroom
like caps, with a skeleton in typical clionaid arrangement. It is distinguished
from congeners by its epibenthic growth form that extends for 20-40 cm above the
substratum, centrally located concentration of oscula, and calcareous fragments
obtained from surrounding sediment that C. tumula sp. nov. incorporates in tracts
that run through the choanosome perpendicular to the ectosome. This species can
be locally abundant in the Florida Keys in patch reefs near sand flats, but may
be restricted to the lower keys as it has not been observed on reefs to the east.
PMID- 25113707
TI - Three new species of the tribe Meconematini (Orthoptera: Tettigoniidae) from
Taiwan.
AB - The paper reported three new species from Taiwan, i.e. Xizicus (Eoxizicus)
taiwanensis sp. nov., Xizicus (Axizicus) falcata sp. nov. and Decma (Decma)
brachyptera sp. nov., supplied the descriptions and illustrations.
PMID- 25113708
TI - New species of Fannia Robineau-Desvoidy (Diptera: Fanniidae) from Colombia.
AB - Fannia Robineau-Desvoidy is a genus of calyptrate Diptera that comprises 89
Neotropical species, of which only 23 occur in Colombia. Based on male characters
(including terminalia), two new species from the Department of Antioquia (Fannia
colazorrensis sp. nov. and Fannia laclara sp. nov.) are described. Illustrations
of the male are presented.
PMID- 25113709
TI - Two new species of Dryophthorinae in the genera Metamasius and Melchus from the
Lesser Antilles (Coleoptera: urculionidae).
AB - Metamasius planatus and Melchus jessae, are described and illustrated from the
Lesser Antilles islands of Dominica and St. Lucia. Metamasius planatus
(Dominica) is distinguished by a relatively flat profile and presence of dense,
very fine, golden micropilosity covering most of the dorsal surface. Melchus
jessae (Dominica and St. Lucia) is the sixth species known in the genus and is
distinguished by the cylindrical rostrum (not laterally compressed apically).
Information on natural history for both species is limited: some Metamasius
planatus and one Melchus jessae were collected in bases of Euterpe globosa
fronds. A revised key to genera of Neotropical Litosomini is presented.
PMID- 25113710
TI - The genus Colletes (Hymenoptera: Apoidea: Colletidae) in Central Asia .
AB - Available information about bees of the genus Colletes in Central Asia is
summarized. Eighty species are currently known from this area. Six new species
are described: Colletes transitus sp. nov., C. askhabadoides sp. nov., C. kaline
sp. nov., C. muellermotzfeldi sp. nov., C. pesenkoi sp. nov., and C. mirabilis
sp. nov. Five species are newly recorded from Central Asia: Colletes idoneus
Cockerell 1922, C. cunicularius (Linnaeus 1761), C. ebmeri Kuhlmann 2002, C.
friesei Cockerell 1918, and C. impunctatus Nylander 1852. The subspecies C.
tuberculatus anatolicus Noskiewicz 1959 syn. nov. and C. t. siculus Noskiewicz
1959 syn. nov. are synonymized with C. tuberculatus Morawitz 1894. Lectotypes are
designated for Colletes arenarius Morawitz 1876 and C. flavicornis Morawitz 1876.
Additionally one new species from Turkey and Iran, Colletes comatoides sp. nov.,
is here described as new and included due to its close relationship to the
Central Asian C. bernadettae Kuhlmann and C. comatus Noskiewicz.
PMID- 25113711
TI - Redescription and lectotype designation of the endemic South African mayfly
Lestagella penicillata (Barnard, 1932) (Ephemeroptera: Teloganodidae).
AB - The imago and nymph of Lestagella penicillata are redescribed based on historic
specimens and new material from Table Mountain slopes (Skeleton Gorge and Window
Stream), Western Cape, South Africa. A male from Barnard's syntype series is
designated as the lectotype. Wear-and-tear of mouthparts, particularly the
mandibles, has led to errors in identification of diagnostic characters for the
nymphs in earlier publications. Previous descriptions of the mandibles being
atrophied, in terms of dentition, are erroneous. The generic diagnosis of
Lestagella is modified to account for these errors and intraspecific variability.
Adults are distinguished from other Teloganodidae by the combination of a short,
detached iMP vein on the forewing, three caudal filaments and gill socket
vestiges on segments II - IV. Nymphs are distinguished from other Teloganodidae
by a conspicuous head fringe, lamellate gills on abdominal segments II-IV and a
dorso-ventrally flattened body.
PMID- 25113712
TI - A molecular phylogeny of the African plated lizards, genus Gerrhosaurus Wiegmann,
1828 (Squamata: Gerrhosauridae), with the description of two new genera.
AB - We constructed a molecular phylogeny of the African plated lizard family
Gerrhosauridae using two mitochondrial markers (ND2, 732 bp; 16S, 576 bp) and one
nuclear marker (PRLR, 538 bp). This analysis showed that the subfamily
Gerrhosaurinae consists of five major clades which we interpret as representing
five genera. The genera Tetradactylus and Cordylosaurus were each recovered as
monophyletic, but Gerrhosaurus as currently conceived is paraphyletic, consisting
of three distinct genus-level assemblages. The two clades consisting of
Gerrhosaurus major Dumeril, 1851 and Gerrhosaurus validus Smith, 1849 are both
described here as new genera, namely Broadleysaurus Bates & Tolley gen. nov. and
Matobosaurus Bates & Tolley gen. nov., respectively. Two subspecies of
'Gerrhosaurus major' that were historically separated on the basis of differences
in colour pattern are not reciprocally monophyletic, so Gerrhosaurus bottegoi Del
Prato, 1895 is relegated to the synonomy of Broadleysaurus major (Dumeril, 1851)
comb. nov., which is rendered monotypic. Gerrhosaurus validus maltzahni De Grys,
1938 is genetically and morphologically well differentiated from G. v. validus
and the two taxa also occur in allopatry. We therefore re-instate the former as
Matobosaurus maltzahni (De Grys, 1938) comb. nov., rendering Matobosaurus validus
(Smith, 1849) comb. nov. a monotypic species. Our analysis also showed that
Gerrhosaurus sensu stricto comprises two major subclades, one consisting of
Gerrhosaurus typicus (Smith, 1837) + Gerrhosaurus skoogi Andersson, 1916, and the
other containing the remaining species. In this latter subclade we show that west
Central African Gerrhosaurus nigrolineatus Hallowell, 1857 is most closely
related to Gerrhosaurus auritus Boettger, 1887 rather than to G. nigrolineatus
from East and Southern Africa. The west-Central African clade of G. nigrolineatus
differs from the East and Southern African clade by a p-distance of 13.0% (ND2)
and 6.9% (16S), and can be differentiated morphologically. We accordingly apply
the name Gerrhosaurus intermedius Lonnberg, 1907 comb. nov. to populations from
Kenya, Uganda, Rwanda, Tanzania, Malawi, Mozambique, Zimbabwe and South Africa
previously identified under the name G. nigrolineatus. Our analysis also confirms
that Gerrhosaurus bulsi Laurent, 1954 is a distinct species and sister taxon to a
clade containing G. nigrolineatus, G. auritus and G. intermedius. The latter four
taxa form a closely-related 'G. nigrolineatus species complex' with a widespread
distribution in Africa. Most closely related to this complex of species is
Gerrhosaurus flavigularis Wiegmann, 1828 which has an extensive range in East and
Southern Africa, and displays genetic substructure which requires further
investigation. The status of Gerrhosaurus multilineatus Bocage, 1866, and Angolan
populations referred to G. nigrolineatus, remains problematic.
PMID- 25113713
TI - Review of the Neotropical species of Stauropoctonus Brauns, 1889 (Hymenoptera:
Ichneumonidae: Ophioninae).
AB - The taxonomy of Neotropical species of Stauropoctonus is reviewed, with
redescriptions of S. bicarinatus and S. excarinatus, the description of four new
Brazilian species, S. amazonensis sp. n., S. leotacilioi sp. n., S. michelle sp.
n., and S. rectus sp. n., and for the first time with a detailed study of the
male genitalia of the genus. Additionally, we provide a key to the world
Stauropoctonus species.
PMID- 25113714
TI - Taxonomic study of the genus Scaphoideus Uhler (Hemiptera, Cicadellidae,
Deltocephalinae) from Japan.
AB - The Japanese species of the genus Scaphoideus are revised. Eight species are
recognized from Japan, including four new species: S. ryukyuensis sp. nov. from
the Ryukyus, S. pristiophorus sp. nov. from Honshu and Kyushu, S. aurantius sp.
nov. from the Ryukyus and S. brevistylus sp. nov. from Honshu, Kyushu and the
Ryukyus.
PMID- 25113715
TI - Bird fossils from Ankilitelo Cave: inference about Holocene environmental changes
in southwestern Madagascar.
AB - The identifications of non-permineralized fossil bird bones recovered from
Ankilitelo Cave in southwestern Madagascar are presented. Among the more than 560
elements recovered, 29 different taxa were identified, the vast majority being
species that still occur in this region of the island. Eggshell remains from the
extinct elephant bird (Family Aepyornithidae) and assigned to Aepyornis sp. were
found at the site. Two identified extant taxa, Scopus umbretta and Monias
benschi, no longer occur in the area immediately surrounding the cave. The
available radiocarbon measurements of collagen from fossil bird bones and avian
eggshell carbonate of recovered from the cave range from 13,270 Cal yr BP to
modern times. Hence, the presumed ecological shifts that took place resulting in
the disappearance or range contractions of these three taxa is within the
Holocene and are presumed to be associated with natural climatic change and in
more recent centuries associated human pressures. Information is also presented
on the origin of guinea fowl (Numida) and inference on the period of colonization
of Corvus albus on Madagascar.
PMID- 25113716
TI - Revision of the Neotropical genus Alloraphes Franz (Coleoptera: Staphylinidae:
Scydmaeninae).
AB - The Neotropical genus Alloraphes Franz belonging to the tribe Cyrtoscydmini is
revised. Alloraphes is redefined based on a detailed morphological study, and
Parastenichnaphes myrmecophilus (Franz) is transferred back to Alloraphes, where
it was originally placed. Alloraphes jamaicae Franz, A. peruanus Franz, A. lenkoi
Franz, A. yucatani Franz, A. chiapasensis Franz and A. myrmecophilus Franz, stat.
rest. are redescribed; A. dentatus sp. n. from Peru and A. peckorum sp. n. from
Bolivia are described. Alloraphes magnus Franz and A. bolivarensis Franz are
treated as species inquirendae pending further study. The placement of
?Alloraphes magnus, known from a single female only, remains unclear. The type
material of A. bolivarensis was not found in the Franz Collection and the
original description hardly allows for the species identification.
PMID- 25113717
TI - A new species of the genus Pristimantis (Amphibia, Craugastoridae) associated
with the moderately elevated massifs of French Guiana.
AB - We describe a new Pristimantis from French Guiana, northern South America, which
is mainly distinguished from known phenotypically related congeners (i.e. species
from the polyphyletic unistrigatus species group) occurring at low and middle
elevations in the Guiana Shield by the combination of a distinct tympanum, a
lower ratio of tibia vs. hand length, a reddish groin region, and a distinct
advertisement call consisting of clusters of generally four short notes. The new
species inhabits pristine primary forests on the slopes of isolated massifs
reaching more than 400 m elevation, and seems not to occur below ca. 200 m above
sea level. Such a sharp altitudinal limit suggests a strong influence of thermal
variation on the distribution of the species, and therefore a potential
sensitivity to climate change. With only nine isolated populations documented so
far, the new species should be prioritized for conservation. Historical climate
fluctuations during the Quaternary are likely responsible for the distribution
pattern of the new species.
PMID- 25113718
TI - The genus Leucophenga (Diptera, Drosophilidae), part III: the interrupta species
group from the Oriental region, with morphological and molecular evidence.
AB - A new species group, the interrupta group, is established within the genus
Leucophenga based on two known and three new species, all of which are endemic to
the Oriental region: L. interrupta Duda, 1924, L. neointerrupta Fartyal & Toda,
2005, L. bifurcata sp. nov., L. quadrifurcata sp. nov. and L. retifoliacea sp.
nov. A key to the five species of the interrupta group is provided. Sixteen mtDNA
COI sequences of the five species are analyzed; the molecular data are used as
complementary evidence for the species boundaries defined by the morphological
data.
PMID- 25113719
TI - WITHDRAWN: The Impact of Skills Training on Cognitive Functioning in Older People
with Serious Mental Illness.
PMID- 25113721
TI - [Infections due to unusual bacteria and bacterial oncogenesis].
AB - The recovery of an unusual organism in the clinical microbiology laboratory may
be an indicator of an immunological abnormality in the patient. For instance, an
important relationship between Clostridium septicum and colon carcinoma as well
as between leukemia or lymphoma with species frequently considered contaminants
(Bacillus spp., Corynebacterium spp.) or others rarely isolated from different
contexts (Capnocytophaga spp.) were described. Some bacteria are almost
exclusively isolated from AIDS patients (Rhodococcus equi). Campylobacter spp.,
Aeromonas spp., group G and mitis group streptococci were more frequently
isolated in individuals suffering from any type of cancer than in other patients.
Furthermore, some other bacteria can be considered markers of an undetected
cancer that can be found mostly in neutropenic patients rather than in
immunologically normal individuals. Possible mechanisms of bacterial oncogenesis
include a modification of the inflammatory response, antigen-derived
lymphoproliferation, and induction of hormones that increase epithelial cell
proliferation. Typical examples of the above are: gastric adenocarcinoma induced
by Helicobacter pylori, the association between group bovis bacteremia and colon
carcinoma and the mucosa-associated lymphoid tissue (MALT) related to
Helicobacter species (gastric MALT) and Chlamydophila spp. (ocular MALT).
Isolation of any of these pathogens should require a thorough search for possible
malignant diseases.
PMID- 25113720
TI - A Longitudinal Study of the Outcome and Associated Factors of Subsyndromal and
Syndromal Depression in Community-Dwelling Older Adults with Schizophrenia
Spectrum Disorder.
AB - OBJECTIVE: Studies examining depression in older adults with schizophrenia have
been limited by cross-sectional data. This study examines longitudinal changes in
depression, predictors of depression, and the impact of depression on clinical
and psychosocial variables in this population. METHODS: The sample consisted of
104 community-dwelling persons with schizophrenia spectrum disorder aged 55 and
over who developed the disorder before age 45. Mean follow-up was 54 months
(range: 12-116 months), mean age was 61 years, 55% were men, and 55% were white.
Presence of subsyndromal or syndromal depression (SSSD) was defined as scoring >7
on the Center for Epidemiologic Studies-Depression Scale (CES-D). RESULTS: There
were no significant differences in SSSD rates between interviews (61% baseline;
54% follow-up); 44% of the sample had SSSD at both assessments, 30% did not have
SSSD at either assessment, 16% went from SSSD to nondepression, and 10% went from
nondepression to SSSD. Similarly, 20%, 27%, and 53% of the sample exhibited >0.5
effect size increase, decrease, or no change, respectively, in their CES-D scores
between assessments. There were two significant time 1 predictors of SSSD at time
2: SSSD and greater number of psychotropic medications. SSSD at time 1 predicted
having higher time 2 anxiety scores. CONCLUSION: Persistent ("core") depression
occurs in about two-fifths of persons, 30% remain persistently nondepressed, and
one-fourth may fluctuate between depression and nondepression. No association was
found between depression and most predictor variables. This study supports recent
findings that schizophrenia in later life is not a quiescent state or one of
affective withdrawal.
PMID- 25113723
TI - Preoperative evaluation of the vascular surgery patient.
AB - Patients undergoing vascular surgery present a myriad of perioperative challenges
due to the complex comorbidities affecting them in conjunction with high-risk
surgical procedures. Additionally, advances in endovascular technology have
enabled surgical procedures to be performed on patients who would not have been
considered surgical candidates in the past. This combination of increasing
patient morbidity and evolving surgical technique requires a well-planned
preoperative assessment and close communication with surgical and perioperative
colleagues. This article outlines an appropriate approach by first considering
each organ system, followed by review of considerations unique to various
surgical procedures, and then an overall assessment of risk.
PMID- 25113724
TI - Optimal perioperative medical management of the vascular surgery patient.
AB - Perioperative medical management of patients undergoing vascular surgery can be
challenging because they represent the surgical population at highest risk. beta
Blockers should be continued perioperatively in patients already taking them
preoperatively. Statins may be used in the perioperative period in patients who
are not on statin therapy preoperatively. Institutional guidelines should be used
to guide insulin replacement. Recent research suggests that measurement of
troponins may provide some risk stratification in clinically stable patients
following vascular surgery. Multimodal pain therapy including nonopioid
strategies is necessary to improve the efficacy of pain relief and decrease the
risk of side effects and complications.
PMID- 25113725
TI - Regional anesthesia for vascular surgery.
AB - Patients presenting for vascular surgery present a challenge to anesthesiologists
because of their severe systemic comorbidities. Regional anesthesia has been used
as a primary anesthetic technique for many vascular procedures to avoid the
cardiovascular and pulmonary perturbations associated with general anesthesia. In
this article the use of regional anesthesia for carotid endarterectomy, open and
endovascular abdominal aortic aneurysm repair, infrainguinal arterial bypass,
lower extremity amputation, and arteriovenous fistula formation is described. A
focus is placed on reviewing the literature comparing anesthetic techniques, with
brief descriptions of the techniques themselves.
PMID- 25113726
TI - Perioperative management of lower extremity revascularization.
AB - Patients presenting for lower extremity revascularization often have multiple
systemic comorbidities, making them high-risk surgical candidates. Neuraxial
anesthesia and general anesthesia are equivocal in their effect on perioperative
cardiac morbidity and improved graft patency. Postoperative epidural analgesia
may improve perioperative cardiac morbidity. Systemic antithrombotic and
anticoagulation therapy is common among this patient population and may affect
anesthetic techniques.
PMID- 25113727
TI - Intraoperative management of carotid endarterectomy.
AB - First reports on surgical treatment of cerebrovascular atherosclerosis date to
the early 1950s. With advancements in surgical technique, carotid endarterectomy
(CEA) has become the treatment of choice for patients with both symptomatic and
asymptomatic severe carotid stenosis. Given the benefits that surgery offers
beyond medical management, the number of CEA procedures continues to increase.
The intraoperative management of patients undergoing CEA is challenging because
of the combination of patient and surgical factors. This article explores and
reviews the literature on anesthetic management and considerations of patients
undergoing CEA.
PMID- 25113728
TI - Perioperative management of combined carotid and coronary artery bypass grafting
procedures.
AB - The objective of this review is to provide a high level overview on current
thinking for treatment of patients with combined carotid and coronary artery
disease given that these patients are at higher risk of adverse cardiac events,
stroke, and death. This review discusses (1) the current literature addressing
perioperative stroke risk in the setting of coronary artery bypass graft, (2) the
literature regarding different surgical approaches when both carotid and coronary
revascularization are being considered, and (3) the data available to guide
optimal management of this complex patient population to minimize complications
regardless of the surgical approach taken.
PMID- 25113729
TI - Considerations for patients undergoing endovascular abdominal aortic aneurysm
repair.
AB - Endovascular aneurysm repair has taken over open surgery as the primary strategy
for treatment of patients with abdominal and thoracic aneurysms. The minimally
invasive nature of these techniques requires alterations in preoperative workup,
intraoperative management, and familiarity with unique complications that can
occur. Familiarity from the anesthetic standpoint of endovascular techniques,
including treatment of patients with fenestrated, chimney, snorkel, and periscope
grafts, is necessary for the contemporary cardiac anesthesiologist.
PMID- 25113730
TI - Postoperative ICU management of vascular surgery patients.
AB - Critical care management of vascular surgical patients poses significant
challenges owing to patients' comorbidities and the magnitude of the surgical
procedures. The primary goals of the anesthesiologist and intensivist are
reestablishing preoperative homeostasis, optimizing hemodynamics until return of
normal organ function, and managing postoperative complications promptly and
effectively. Postoperative critical care management demands a detailed knowledge
of the various vascular surgical procedures and the potential postoperative
complications. In this review, the authors describe the postoperative
complications related to the major specific vascular surgical procedures and
their perioperative management.
PMID- 25113732
TI - Vascular anesthesia. Preface.
PMID- 25113734
TI - Structure and photoluminescence studies of CeO2.CuAlO2 mixed metal oxide
fabricated by co-precipitation method.
AB - A novel mixed metal oxide, CeO2.CuAlO2 was fabricated by co-precipitation method
in aqueous medium. CeO2.CuAlO2 was characterized by XRD, SEM, EDS, TEM, FTIR and
PL spectra. The optical properties of the nanoparticles were studied by
photoluminescence (PL) spectra. PL spectra at different excitations were
recorded. The composite showed emission in UV, visible and NIR region depending
on the excitation wavelength. The special spectral feature observed for this
composite is that it showed six emission bands at 364, 409, 434, 448, 465 and 481
nm when excited at 298 nm. The green and red emissions observed at 512 and 669 nm
are originated from cubic CeO2 phase when excited at 450 nm. The PL spectra were
found to be dependent on excitation wavelength violating Kasha's rule. The X-ray
diffraction reveals a cubic CeO2 phase and hexagonal CuAlO2 phase. EDS spectra
revealed the presence of cerium (Ce), copper (Cu), aluminum (Al) and oxygen (O)
elements. The particle size of the CeO2.CuAlO2 mixed oxide was estimated using
Scherrer's formula, which was found to be in the range of 17.2-34.2 nm. The TEM
image showed particles are almost uniform size of approximately 15-50 nm with
spherical morphology.
PMID- 25113733
TI - Continuous dopaminergic stimulation (CDS)-based treatment in Parkinson's disease
patients with motor complications: a systematic review and meta-analysis.
AB - A systematic review of the literature was conducted to identify randomized trials
involving continuous dopaminergic stimulation (CDS) in PD patients with motor
complications. Difference between n groups was assessed by partitioning
heterogeneity and using the chi2 distribution with n-1 degrees of freedom, where
n equals the number of groups. We looked for publication bias using funnel
plotting, Egger's test and Begg's test. Twenty Randomized Controlled Trials
(RCTs) were included. The results showed that CDS could evidently improve the
Unified Parkinson's Disease Rating Scale (UPDRS) Part II (p < 0.0001), part III
(P < 0.00001) and UPDRS total score (p < 0.00001). There was also a statistical
discrepancy in off time reduction (p < 0.00001) and prolongation of on time (p <
0.00001) by the CDS therapy compared with control groups. Meanwhile, the results
of this study showed obvious side effects in the CDS therapy compared with the
placebo, especially at the expense of increased dyskinesia (23.4% vs 11.7%). The
present study showed that CDS was beneficial in the treatment of PD patients with
motor complications. But the incidence of the side events is more common than
placebo.
PMID- 25113735
TI - Validated spectrofluorimetric method for determination of selected
aminoglycosides.
AB - New, sensitive, and selective spectrofluorimetric method was developed for
determination of three aminoglycoside drugs in different dosage forms, namely;
neomycin sulfate (NEO), tobramycin (TOB) and kanamycin sulfate (KAN). The method
is based on Hantzsch condensation reaction between the primary amino group of
aminoglycosides with acetylacetone and formaldehyde in pH 2.7 yielding highly
yellow fluorescent derivatives measured emission (471 nm) and excitation (410 nm)
wavelengths. The fluorescence intensity was directly proportional to the
concentration over the range 10-60, 40-100 and 5-50 ng/mL for NEO, TOB and KAN
respectively. The proposed method was applied successfully for determination of
these drugs in their pharmaceutical dosage forms.
PMID- 25113737
TI - Switchable regioselectivity in the PIFA-BF3.Et2O mediated oxidative coupling of
meso-brominated Ni(II) porphyrin.
AB - A simple and efficient method has been developed for the switchable synthesis of
directly linked meso-brominated Ni(II) porphyrin dimers through PIFA-BF3.Et2O
mediated oxidative coupling. The respective syntheses of meso-meso or meso-beta
singly, doubly, and triply linked porphyrin dimers can be easily realized with
the same reagent system.
PMID- 25113736
TI - Application of central composite design for simultaneous removal of methylene
blue and Pb(2+) ions by walnut wood activated carbon.
AB - Activated carbon was prepared from walnut wood which was locally available, non
toxic, abundant and cheap. This new adsorbent was characterized using BET, FTIR
and SEM. Point of zero charge (pHpzc) and oxygen containing functional groups
were also determined. The prepared adsorbent was applied for simultaneous removal
of Pb(2+) ions and methylene blue (MB) dye from aqueous solution. The prominent
effect and interaction of variables such as amount of adsorbent, contact time,
concentration of MB and Pb(2+) ions were optimized by central composite design.
The equilibrium data obtained at optimum condition were fitted to conventional
isotherm models and found that Langmuir model was the best fitted isotherm.
Kinetic data were fitted using various models. It was revealed that the
adsorption rate follows pseudo-second order kinetic model and intraparticle
diffusion model.
PMID- 25113738
TI - Synthesis of a poly-pendant 1-D chain based on 'trans-vanadium' bicapped, Keggin
type vanadtungstate and its photocatalytic properties.
AB - A vanadtungstate cluster-based organic-inorganic hybrid material
[NiL4V(IV)W(VI)10W(V)2O40(V(IV)O)2] (1, L = 1,4-bis(imidazol-1-ylmethyl)benzene)
was synthesized and characterized by elemental analysis, IR spectra, thermal
gravimetric analysis, and single crystal X-ray diffraction analysis. Structural
analysis reveals that compound 1 contains a transition metal-centered, bicapped
Keggin-type {VW12O40(VO)2} core, connected by nickel linkers into a 1-D chain.
These 1D chains interdigitated with each other, achieving an interdigitated 3D
supermolecular architecture. Photocatalytic studies indicate that compound 1
exhibits not only active photocatalytic degradation of dye molecules, but also
selective photocatalytic activity for degradation of cationic dyes in aqueous
solution. Further, this photocatalyst is stable and easily separated from the
photocatalytic system for reuse as well.
PMID- 25113739
TI - Inverse association between cancer and neurodegenerative disease: review of the
epidemiologic and biological evidence.
AB - Growing evidence suggests an unusual epidemiologic association between cancer and
certain neurological conditions, particularly age-related neurodegenerative
diseases. Cancer survivors have a 20-50% lower risk of developing Parkinson's and
Alzheimer's disease, and patients with these neurodegenerative conditions have a
substantially lower incidence of cancer. We review the epidemiologic evidence for
this inverse co-morbidity and show that it is not simply an artifact of survival
bias or under-diagnosis. We then review the potential biological explanations for
this association, which is intimately linked to the very different nature of
dividing cells and neurons. The known genetic and metabolic connections between
cancer and neurodegeneration generally fall within two categories. The first
includes shared genes and pathways such as Pin1 and the ubiquitin proteasome
system that are dysregulated in different directions to cause one disease or the
other. The second includes common pathophysiological mechanisms such as
mitochondrial dysfunction, oxidative stress and DNA damage that drive both
conditions, but with different cellular fates. We discuss examples of these
biological links and their implications for developing new approaches to
prevention and treatment of both diseases.
PMID- 25113740
TI - International recognition for ageing research: John Scott Award-2014 to Leonard
Hayflick and Paul Moorhead.
PMID- 25113741
TI - Does bird species diversity vary among forest types? A local-scale test in
southern Chile.
AB - Birds are the most diverse vertebrate group in Chile, characterized by low
species turnover at the country-size scale (high alpha but low beta diversities),
resembling an island biota. We tested whether this low differentiation is valid
at a local scale, among six forest habitat types. We detected 25 bird species;
avifauna composition was significantly different among habitat types, with five
species accounting for 60% of the dissimilarity. We found a higher level of bird
assemblage differentiation across habitats at the local scale than has been found
at the country-size scale. Such differentiation might be attributed to structural
differences among habitats.
PMID- 25113742
TI - Streptococcal pharyngitis in children: to treat or not to treat?
AB - Controversy remains about the need for antibiotic therapy of group A
streptococcal (GAS) pharyngitis in high-resource settings. Guidelines on the
management of GAS pharyngitis differ considerably, especially in children. We
performed a literature search on the diagnosis and treatment of GAS pharyngitis
in children and compared different guidelines with current epidemiology and the
available evidence on management. Some European guidelines only recommend
antibiotic treatment in certain high-risk patients, while many other, including
all American, still advise antimicrobial treatment for all children with GAS
pharyngitis, given the severity and re-emerging incidence of complications.
Empirical antimicrobial treatment in children with sore throat and a high
clinical suspicion of GAS pharyngitis will still result in significant
overtreatment of nonstreptococcal pharyngitis. This is costly and leads to
emerging antibiotic resistance. Early differential diagnosis between viral and
GAS pharyngitis, by means of a 'rapid antigen detection test' (RADT) and/or a
throat culture, is therefore needed if 'pro treatment' guidelines are used.
CONCLUSION: Large scale randomized controlled trials are necessary to assess the
value of antibiotics for GAS pharyngitis in high-resource countries, in order to
achieve uniform and evidence-based guidelines. The severity and the possibly
increasing incidence of complications in school-aged children suggests that
testing and treating proven GAS pharyngitis can still be beneficial.
PMID- 25113743
TI - Inclusion of mobile telephone numbers into an ongoing population health survey in
New South Wales, Australia, using an overlapping dual-frame design: impact on the
time series.
AB - BACKGROUND: Since 1997, the NSW Population Health Survey (NSWPHS) had selected
the sample using random digit dialing of landline telephone numbers. When the
survey began coverage of the population by landline phone frames was high (96%).
As landline coverage in Australia has declined and continues to do so, in 2012, a
sample of mobile telephone numbers was added to the survey using an overlapping
dual-frame design. Details of the methodology are published elsewhere. This paper
discusses the impacts of the sampling frame change on the time series, and
provides possible approaches to handling these impacts. METHODS: Prevalence
estimates were calculated for type of phone-use, and a range of health
indicators. Prevalence ratios (PR) for each of the health indicators were also
calculated using Poisson regression analysis with robust variance estimation by
type of phone-use. Health estimates for 2012 were compared to 2011. The full time
series was examined for selected health indicators. RESULTS: It was estimated
from the 2012 NSWPHS that 20.0% of the NSW population were mobile-only phone
users. Looking at the full time series for overweight or obese and current
smoking if the NSWPHS had continued to be undertaken only using a landline frame,
overweight or obese would have been shown to continue to increase and current
smoking would have been shown to continue to decrease. However, with the
introduction of the overlapping dual-frame design in 2012, overweight or obese
increased until 2011 and then decreased in 2012, and current smoking decreased
until 2011, and then increased in 2012. Our examination of these time series
showed that the changes were a consequence of the sampling frame change and were
not real changes. Both the backcasting method and the minimal coverage method
could adequately adjust for the design change and allow for the continuation of
the time series. CONCLUSIONS: The inclusion of the mobile telephone numbers,
through an overlapping dual-frame design, did impact on the time series for some
of the health indicators collected through the NSWPHS, but only in that it
corrected the estimates that were being calculated from a sample frame that was
progressively covering less of the population.
PMID- 25113744
TI - Altered phenotype and Stat1 expression in Toll-like receptor 7/8 stimulated
monocyte-derived dendritic cells from patients with primary Sjogren's syndrome.
AB - INTRODUCTION: Dendritic cells (DC) are the most potent antigen-presenting cells
of the immune system, involved in both initiating immune responses and
maintaining tolerance. Dysfunctional and via toll-like receptor (TLR) ligands
activated DC have been implicated in the development of autoimmune diseases, but
their role in the etiology of Sjogren's syndrome, a chronic inflammatory
autoimmune disease characterized by progressive mononuclear cell infiltration in
the exocrine glands, has not been revealed yet. Therefore, the aim of this study
was to investigate phenotype and functional properties of immature and TLR7/8
stimulated monocyte-derived DC (moDC) of patients with primary Sjogren's syndrome
(pSS) and compare them to healthy controls. METHODS: The phenotype, apoptosis
susceptibility and endocytic capacity of moDC were analyzed by flow cytometry.
Secretion of cytokines was measured by enzyme-linked immunosorbent assay (ELISA)
and multiplex Luminex analyses in moDC cell culture supernatants. The expression
of TLR7 was analyzed by flow cytometry and real-time quantitative polymerase
chain reaction (qPCR). Expression of Ro/Sjogren's syndrome-associated autoantigen
A (Ro52/SSA), interferon regulatory factor 8 (IRF-8), Bim, signal transduction
and activators of transcription (Stat) 1, p-Stat1 (Tyrosin 701), p-Stat1 (Serin
727), Stat3, pStat3 (Tyrosin 705) and glyceraldehyde 3-phosphatase dehydrogenase
(GAPDH) was measured by Western blotting. Nuclear factor kappa-light-chain
enhancer of activated B cells (NF-kappaB) family members were quantified using
the ELISA-based TransAM NF-kappaB family kit. RESULTS: We could not detect
differences in expression of co-stimulatory molecules and maturation markers such
as cluster of differentiation (CD) 86, CD80, CD40 or CD83 on moDC from patients
compared to healthy controls. Moreover, we could not observe variations in
apoptosis susceptibility, Bim and Ro52/SSA expression and the endocytic capacity
of the moDC. However, we found that moDC from pSS patients expressed increased
levels of the major histocompatibility complex (MHC) class II molecule human
leukocyte antigen (HLA)-DR. We also found significant differences in cytokine
production by moDC, where increased interleukin (IL)-12p40 secretion in mature
pSS moDC correlated with increased RelB expression. Strikingly, moDC from pSS
patients matured for 48 hours with TLR7/8 ligand CL097 expressed significantly
less Stat1. CONCLUSION: Our results suggest a role for moDC in the pathogenesis
of Sjogren's syndrome.
PMID- 25113745
TI - Chikungunya virus was isolated in Thailand, 2010.
AB - Chikungunya fever (CHIKF) is an acute febrile illness caused by a mosquito-borne
alphavirus, chikungunya virus (CHIKV). This disease re-emerged in Kenya in 2004,
and spread to the countries in and around the Indian Ocean. The re-emerging
epidemics rapidly spread to regions like India and Southeast Asia, and it was
subsequently identified in Europe in 2007, probably as a result of importation of
chikungunya cases. On the one hand, chikungunya is one of the neglected diseases
and has only attracted strong attention during large outbreaks. In 2008-2009,
there was a major outbreak of chikungunya fever in Thailand, resulting in the
highest number of infections in any country in the region. However, no update of
CHIKV circulating in Thailand has been published since 2009. In this study, we
examined the viral growth kinetics and sequences of the structural genes derived
from CHIKV clinical isolates obtained from the serum specimens of CHIKF-suspected
patients in Central Thailand in 2010. We identified the CHIKV harboring two
mutations E1-A226V and E2-I211T, indicating that the East, Central, and South
African lineage of CHIKV was continuously circulating as an indigenous population
in Thailand.
PMID- 25113746
TI - A murine model of neurofibromatosis type 2 that accurately phenocopies human
schwannoma formation.
AB - Neurofibromatosis type 2 (NF2) is an autosomal dominant genetic disorder
resulting from germline mutations in the NF2 gene. Bilateral vestibular
schwannomas, tumors on cranial nerve VIII, are pathognomonic for NF2 disease.
Furthermore, schwannomas also commonly develop in other cranial nerves, dorsal
root ganglia and peripheral nerves. These tumors are a major cause of morbidity
and mortality, and medical therapies to treat them are limited. Animal models
that accurately recapitulate the full anatomical spectrum of human NF2-related
schwannomas, including the characteristic functional deficits in hearing and
balance associated with cranial nerve VIII tumors, would allow systematic
evaluation of experimental therapeutics prior to clinical use. Here, we present a
genetically engineered NF2 mouse model generated through excision of the Nf2 gene
driven by Cre expression under control of a tissue-restricted 3.9kbPeriostin
promoter element. By 10 months of age, 100% of Postn-Cre; Nf2(flox/flox) mice
develop spinal, peripheral and cranial nerve tumors histologically identical to
human schwannomas. In addition, the development of cranial nerve VIII tumors
correlates with functional impairments in hearing and balance, as measured by
auditory brainstem response and vestibular testing. Overall, the Postn-Cre;
Nf2(flox/flox) tumor model provides a novel tool for future mechanistic and
therapeutic studies of NF2-associated schwannomas.
PMID- 25113749
TI - Coronary artery disease: Predicting the progression of coronary artery
calcification.
PMID- 25113747
TI - Dyclonine rescues frataxin deficiency in animal models and buccal cells of
patients with Friedreich's ataxia.
AB - Inherited deficiency in the mitochondrial protein frataxin (FXN) causes the rare
disease Friedreich's ataxia (FA), for which there is no successful treatment. We
identified a redox deficiency in FA cells and used this to model the disease. We
screened a 1600-compound library to identify existing drugs, which could be of
therapeutic benefit. We identified the topical anesthetic dyclonine as
protective. Dyclonine increased FXN transcript and FXN protein dose-dependently
in FA cells and brains of animal models. Dyclonine also rescued FXN-dependent
enzyme deficiencies in the iron-sulfur enzymes, aconitase and succinate
dehydrogenase. Dyclonine induces the Nrf2 [nuclear factor (erythroid-derived 2)
like 2] transcription factor, which we show binds an upstream response element in
the FXN locus. Additionally, dyclonine also inhibited the activity of histone
methyltransferase G9a, known to methylate histone H3K9 to silence FA chromatin.
Chronic dosing in a FA mouse model prevented a performance decline in balance
beam studies. A human clinical proof-of-concept study was completed in eight FA
patients dosed twice daily using a 1% dyclonine rinse for 1 week. Six of the
eight patients showed an increase in buccal cell FXN levels, and fold induction
was significantly correlated with disease severity. Dyclonine represents a novel
therapeutic strategy that can potentially be repurposed for the treatment of FA.
PMID- 25113748
TI - An ALS-mutant TDP-43 neurotoxic peptide adopts an anti-parallel beta-structure
and induces TDP-43 redistribution.
AB - TDP-43 proteinopathies are clinically and genetically heterogeneous diseases that
had been considered distinct from classical amyloid diseases. Here, we provide
evidence for the structural similarity between TDP-43 peptides and other amyloid
proteins. Atomic force microscopy and electron microscopy examination of peptides
spanning a previously defined amyloidogenic fragment revealed a minimal core
region that forms amyloid fibrils similar to the TDP-43 fibrils detected in FTLD
TDP brain tissues. An ALS-mutant A315E amyloidogenic TDP-43 peptide is capable of
cross-seeding other TDP-43 peptides and an amyloid-beta peptide. Sequential
Nuclear Overhauser Effects and double-quantum-filtered correlation spectroscopy
in nuclear magnetic resonance (NMR) analyses of the A315E-mutant TDP-43 peptide
indicate that it adopts an anti-parallel beta conformation. When added to cell
cultures, the amyloidogenic TDP-43 peptides induce TDP-43 redistribution from the
nucleus to the cytoplasm. Neuronal cultures in compartmentalized microfluidic
chambers demonstrate that the TDP-43 peptides can be taken up by axons and induce
axonotoxicity and neuronal death, thus recapitulating key neuropathological
features of TDP-43 proteinopathies. Importantly, a single amino acid change in
the amyloidogenic TDP-43 peptide that disrupts fibril formation also eliminates
neurotoxicity, supporting that amyloidogenesis is critical for TDP-43
neurotoxicity.
PMID- 25113751
TI - Trials of implantable monitoring devices in heart failure: which design is
optimal?
AB - Implantable monitoring devices have been developed to detect early evidence of
heart failure (HF) decompensation, with the hypothesis that early detection might
enable clinicians to commence therapy sooner than would otherwise be possible,
and potentially to reduce the rate of hospitalization. In addition to the usual
challenges inherent to device trials (such as the difficulty of double-blinding
and potential for bias), studies of implantable monitoring devices present unique
difficulties because they involve assessment of therapeutic end points for
diagnostic devices. Problems include the lack of uniform approaches to treatment
in study protocols for device alerts or out-of-range values, and the requirement
of levels of evidence traditionally associated with therapeutic devices to
establish effectiveness and safety. In this Review, the approaches used to deal
with these issues are discussed, including the use of objective primary end
points with blinded adjudication, identical duration of follow-up and number of
encounters for patients in active monitoring and control groups, and treatment
recommendations between groups that are consistent with international guidelines.
Remote monitoring devices hold promise for reducing the rate of hospitalization
among patients with HF. However, optimization of regulatory approaches and
clinical trial design is needed to facilitate further evaluation of the
effectiveness of combining health information technology and medical devices.
PMID- 25113752
TI - Acute improvement of left ventricular relaxation as a predictor of volume
reduction after cardiac resynchronization therapy: a pilot study assessing the
value of left ventricular hemodynamic parameter.
AB - BACKGROUND: Cardiac resynchronization therapy (CRT) improves cardiac function,
but CRT recipients with advanced heart failure (HF) do not always respond well.
Because the best parameters for the prediction of CRT response are not
established, we investigated whether improvement of invasive left ventricular
(LV) hemodynamic diastolic parameters could identify CRT responders. METHODS: A
total of 34 consecutive patients (age, 69 +/- 9 years; 70% men) who received CRT
devices for HF were assessed as to whether acute invasive hemodynamic parameters
with and without CRT function could predict LV volume responders. RESULTS: These
patients demonstrated an improvement in LV dP/dtmax (11.1 +/- 11.7%), LV dP/dtmin
(4.6 +/- 12.1%), and tau (3.7 +/- 11.6%) by biventricular pacing. Nineteen
patients (55%) were classified as CRT responders, which was defined by a >15%
decrease in LV end-systolic volume (ESV) at the 6-month follow-up evaluation. The
area under the receiver operator characteristic curve to detect CRT volume
response was 0.93 for the shortening of tau, which was superior to any other
hemodynamic parameter. The multivariate analysis revealed that this improvement
in tau was the strongest predictive factor for identifying CRT volume responders.
Of note, the magnitude of tau shortening during biventricular pacing was
significantly correlated with the reduction in LVESV at the 6-month follow-up
evaluation. CONCLUSIONS: The extent of acute improvement in LV isovolumic
relaxation time, as assessed by tau, was associated with favorable response to
CRT. The assessment of invasive diastolic function could provide valuable
information about CRT volume response.
PMID- 25113750
TI - Global epidemiology of atrial fibrillation.
AB - Atrial fibrillation (AF) is a major public health burden worldwide, and its
prevalence is set to increase owing to widespread population ageing, especially
in rapidly developing countries such as Brazil, China, India, and Indonesia.
Despite the availability of epidemiological data on the prevalence of AF in North
America and Western Europe, corresponding data are limited in Africa, Asia, and
South America. Moreover, other observations suggest that the prevalence of AF
might be underestimated-not only in low-income and middle-income countries, but
also in their high-income counterparts. Future studies are required to provide
precise estimations of the global AF burden, identify important risk factors in
various regions worldwide, and take into consideration regional and ethnic
variations in AF. Furthermore, in response to the increasing prevalence of AF,
additional resources will need to be allocated globally for prevention and
treatment of AF and its associated complications. In this Review, we discuss the
available data on the global prevalence, risk factors, management, financial
costs, and clinical burden of AF, and highlight the current worldwide inadequacy
of its treatment.
PMID- 25113754
TI - Retrospective propensity score matching and the selection of surgical procedures:
how precise can a propensity estimate be?
PMID- 25113755
TI - Reply to M. Honda et al.
PMID- 25113753
TI - Recommendations for initial evaluation, staging, and response assessment of
Hodgkin and non-Hodgkin lymphoma: the Lugano classification.
AB - The purpose of this work was to modernize recommendations for evaluation,
staging, and response assessment of patients with Hodgkin lymphoma (HL) and non
Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference
on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading
hematologists, oncologists, radiation oncologists, pathologists, radiologists,
and nuclear medicine physicians, representing major international lymphoma
clinical trials groups and cancer centers. Clinical and imaging subcommittees
presented their conclusions at a subsequent workshop at the 12th International
Conference on Malignant Lymphoma, leading to revised criteria for staging and of
the International Working Group Guidelines of 2007 for response. As a result,
fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography
(CT) was formally incorporated into standard staging for FDG-avid lymphomas. A
modification of the Ann Arbor descriptive terminology will be used for anatomic
distribution of disease extent, but the suffixes A or B for symptoms will only be
included for HL. A bone marrow biopsy is no longer indicated for the routine
staging of HL and most diffuse large B-cell lymphomas. However, regardless of
stage, general practice is to treat patients based on limited (stages I and II,
nonbulky) or advanced (stage III or IV) disease, with stage II bulky disease
considered as limited or advanced disease based on histology and a number of
prognostic factors. PET-CT will be used to assess response in FDG-avid
histologies using the 5-point scale. The product of the perpendicular diameters
of a single node can be used to identify progressive disease. Routine
surveillance scans are discouraged. These recommendations should improve
evaluation of patients with lymphoma and enhance the ability to compare outcomes
of clinical trials.
PMID- 25113757
TI - Targeting inhibitor of apoptosis proteins for cancer therapy: a double-edge
sword?
PMID- 25113756
TI - Phase I dose-escalation study of LCL161, an oral inhibitor of apoptosis proteins
inhibitor, in patients with advanced solid tumors.
AB - PURPOSE: LCL161 antagonizes the function of inhibitor of apoptosis proteins
(IAPs), thereby promoting cancer cell death. This first-in-human dose-escalation
study assessed the maximum-tolerated dose (MTD), safety, pharmacokinetics, and
pharmacodynamics of LCL161 in patients with advanced solid tumors. A second part
of the study assessed the relative bioavailability of a tablet versus solution
formulation. PATIENTS AND METHODS: LCL161 was administered orally, once weekly,
on a 21-day cycle to adult patients with advanced solid tumors by using an
adaptive Bayesian logistic regression model with overdose control-guided dose
escalation. RESULTS: Fifty-three patients received at least one dose of LCL161
(dose range, 10 to 3,000 mg). LCL161 was well tolerated at doses up to 1,800 mg.
Cytokine release syndrome (CRS) was the only dose-limiting toxicity (in three
[6%] of 53 patients) and was the most common grades 3 to 4 event (in five [9%] of
53 patients). Vomiting, nausea, asthenia/fatigue, and anorexia were common but
not severe. Although the MTD was not formally determined, an 1,800-mg dose was
selected in compliance with the protocol for additional study, given the dose
limiting CRS at higher doses and pharmacodynamic activity at lower doses. LCL161
was rapidly absorbed, and exposure was generally increased with dose. The tablet
formulation of LCL161 was better tolerated than the solution; tablet and solution
formulations had similar exposures, and the solution was discontinued. No patient
had an objective response. LCL161 induced degradation of cellular IAP1 protein in
the blood, skin, and tumor and increased circulating cytokine levels. CONCLUSION:
The 1,800-mg dose of LCL161, administered as a single agent once weekly, in
tablet formulation is the recommended dose for additional study. This combined
dose and formulation was well tolerated and had significant pharmacodynamic
activity, which warrants additional investigation.
PMID- 25113758
TI - Stereotactic body radiation therapy as a derivative of stereotactic radiosurgery:
clinically independent but with enduring common themes.
PMID- 25113759
TI - Value: a framework for radiation oncology.
AB - In the current health care system, high costs without proportional improvements
in quality or outcome have prompted widespread calls for change in how we deliver
and pay for care. Value-based health care delivery models have been proposed.
Multiple impediments exist to achieving value, including misaligned patient and
provider incentives, information asymmetries, convoluted and opaque cost
structures, and cultural attitudes toward cancer treatment. Radiation oncology as
a specialty has recently become a focus of the value discussion. Escalating costs
secondary to rapidly evolving technologies, safety breaches, and variable,
nonstandardized structures and processes of delivering care have garnered
attention. In response, we present a framework for the value discussion in
radiation oncology and identify approaches for attaining value, including
economic and structural models, process improvements, outcome measurement, and
cost assessment.
PMID- 25113760
TI - Patient-reported outcomes and survivorship in radiation oncology: overcoming the
cons.
AB - PURPOSE: Although patient-reported outcomes (PROs) have become a key component of
clinical oncology trials, many challenges exist regarding their optimal
application. The goal of this article is to methodically review these barriers
and suggest strategies to overcome them. This review will primarily focus on
radiation oncology examples, will address issues regarding the "why, how, and
what" of PROs, and will provide strategies for difficult problems such as methods
for reducing missing data. This review will also address cancer survivorship
because it closely relates to PROs. METHODS: Key articles focusing on PROs,
quality of life, and survivorship issues in oncology trials are highlighted, with
an emphasis on radiation oncology clinical trials. Publications and Web sites of
various governmental and regulatory agencies are also reviewed. RESULTS: The
study of PROs in clinical oncology trials has become well established. There are
guidelines provided by organizations such as the US Food and Drug Administration
that clearly indicate the importance of and methodology for studying PROs.
Clinical trials in oncology have repeatedly demonstrated the value of studying
PROs and suggested ways to overcome some of the key challenges. The Radiation
Therapy Oncology Group (RTOG) has led some of these efforts, and their
contributions are highlighted. The current state of cancer survivorship
guidelines is also discussed. CONCLUSION: The study of PROs presents significant
benefits in understanding and treating toxicities and enhancing quality of life;
however, challenges remain. Strategies are presented to overcome these hurdles,
which will ultimately improve cancer survivorship.
PMID- 25113761
TI - Emergence of stereotactic body radiation therapy and its impact on current and
future clinical practice.
AB - Stereotactic body radiation therapy (SBRT) is generally a tumor-ablative
radiation modality using essential technologies capable of accurately and
precisely damaging the target with a high dose while geometrically sparing
innocent normal tissues. The intent, conduct, and tissue biology are all
dramatically distinct from conventionally fractionated radiotherapy such that new
understanding is required for its optimization. It is most practical, tolerable,
and tumoricidal in its most potent form treating tumors in the lung and liver.
However, it is increasingly being used for tumors adjacent to bowels and nervous
tissue, albeit with somewhat less ablative potency. Its strengths include high
rates of tumor eradication via a noninvasive, convenient outpatient treatment.
Its weakness relates to the possibility of causing difficult-to-manage toxicity
(eg, ulceration, stenosis, fibrosis, and even necrosis) that may occur
considerably later after treatment, particularly in the vicinity of the body's
many tubular structures (eg, organ hila, bowel). However, clinical trials in a
variety of organs and sites have shown SBRT to result in good outcomes in
properly selected patients. Given its short course, lack of need for recovery,
and favorable overall toxicity profile, there is great hope that SBRT will find a
prominent place in the treatment of metastatic cancer as a consolidative partner
with systemic therapy. With considerable published experience, available required
technologies and training, and many patients in need of local therapy, SBRT has
found a place in the routine cancer-fighting arsenal.
PMID- 25113763
TI - Psychosexual functioning among adult female survivors of childhood cancer: a
report from the childhood cancer survivor study.
AB - PURPOSE: Childhood cancer survivors may be at risk for impaired psychosexual
functioning as a direct result of their cancer or its treatments, psychosocial
difficulties, and/or diminished quality of life. PATIENTS AND METHODS: Two
thousand one hundred seventy-eight female adult survivors of childhood cancer and
408 female siblings from the Childhood Cancer Survivor Study (CCSS) completed a
self-report questionnaire about their psychosexual functioning and quality of
life. On average, participants were age 29 years (range, 18 to 51 years) at the
time of the survey, had been diagnosed with cancer at a median age of 8.5 years
(range, 0 to 20) and were most commonly diagnosed with leukemia (33.2%) and
Hodgkin lymphoma (15.4%). RESULTS: Multivariable analyses suggested that after
controlling for sociodemographic differences, survivors reported significantly
lower sexual functioning (mean difference [MnD], -0.2; P = .01), lower sexual
interest (MnD, -0.2; P < .01), lower sexual desire (MnD, -0.3; P < .01), lower
sexual arousal (MnD, -0.3; P < .01), lower sexual satisfaction (MnD, -0.2; P =
.01), and lower sexual activity (MnD, -0.1; P = .02) compared with siblings. Risk
factors for poorer psychosexual functioning among survivors included older age at
assessment, ovarian failure at a younger age, treatment with cranial radiation,
and cancer diagnosis during adolescence. CONCLUSION: Decreased sexual functioning
among female survivors of childhood cancers seems to be unrelated to emotional
factors and is likely to be an underaddressed issue. Several risk factors among
survivors have been identified that assist in defining high-risk subgroups who
may benefit from targeted screening and interventions.
PMID- 25113764
TI - Frontiers in radiotherapy for early-stage invasive breast cancer.
AB - The development of breast-conserving treatment for early-stage breast cancer is
one of the most important success stories in radiation oncology in the latter
half of the twentieth century. Lumpectomy followed by radiotherapy provides an
appealing alternative to mastectomy for many women. In recent years, there has
been a shift in clinical investigational focus toward refinements in the methods
of delivering adjuvant radiotherapy that provide shorter, more convenient
schedules of external-beam radiotherapy and interstitial treatment. Expedited
courses of whole-breast treatment have been demonstrated to be equivalent to
traditional lengthier courses in terms of tumor control and cosmetic outcome and
to provide an opportunity for cost efficiencies.
PMID- 25113762
TI - Cranial stereotactic radiosurgery: current status of the initial paradigm
shifter.
AB - The concept of stereotactic radiosurgery (SRS) was first described by Lars
Leksell in 1951. It was proposed as a noninvasive alternative to open
neurosurgical approaches to manage a variety of conditions. In the following
decades, SRS emerged as a unique discipline involving a collegial partnership
among neurosurgeons, radiation oncologists, and medical physicists. SRS relies on
the precisely guided delivery of high-dose ionizing radiation to an intracranial
target. The focused convergence of multiple beams yields a potent therapeutic
effect on the target and a steep dose fall-off to surrounding structures, thereby
minimizing the risk of collateral damage. SRS is typically administered in a
single session but can be given in as many as five sessions or fractions. By
providing an ablative effect noninvasively, SRS has altered the treatment
paradigms for benign and malignant intracranial tumors, functional disorders, and
vascular malformations. Literature on extensive intracranial radiosurgery has
unequivocally demonstrated the favorable benefit-to-risk profile that SRS affords
for appropriately selected patients. In a departure from conventional
radiotherapeutic strategies, radiosurgical principles have recently been extended
to extracranial indications such as lung, spine, and liver tumors. The paradigm
shift resulting from radiosurgery continues to alter the landscape of related
fields.
PMID- 25113766
TI - Enhancing the efficacy of radiation therapy: premises, promises, and
practicality.
PMID- 25113767
TI - Impact of informative censoring on the Kaplan-Meier estimate of progression-free
survival in phase II clinical trials.
AB - Informative censoring in a progression-free survival (PFS) analysis arises when
patients are censored for initiation of an effective anticancer treatment before
the protocol-defined progression, and these patients are at a different risk for
treatment failure than those who continue on therapy. This may cause bias in the
estimated PFS when using the Kaplan-Meier method for analysis. Although there are
several articles that discuss this issue from a theoretical perspective or in
randomized phase III studies, there are little data to demonstrate the magnitude
of the bias on the estimated quantities from a phase II trial. This article
describes the issues by using two oncology phase II trials as examples, evaluates
the impact of the bias using simulations, and provides recommendations. The two
trials were selected because they demonstrate two different reasons for
censoring. Simulations show that the magnitude of the bias depends primarily on
the proportion of patients who are informatively censored and secondarily on the
hazard ratio between the group of patients who remain on study and the group of
patients who are informatively censored. Recommendations include using an
alternative end point, which includes inadequate response and initial signs of
clinical progression as treatment failure, and a competing risk analysis for
studies in which competing events preclude or modify the probability of observing
the primary event of interest. If informative censoring cannot be avoided, then
all patients should be observed until progression, and sensitivity analyses
should be used as appropriate.
PMID- 25113765
TI - Radical irradiation of extracranial oligometastases.
AB - Advances in radiotherapy planning and delivery have been used to treat patients
with limited metastatic disease. With these techniques, high rates of treated
metastasis control and low toxicity have been reported. Some patients have long
disease-free intervals after radiotherapy similar to those seen after surgical
resection. Ongoing studies will determine the benefit of these irradiation
techniques to treat limited metastases, identify appropriate candidates, and
assist in integrating these treatments into management strategies for specific
diseases.
PMID- 25113768
TI - Molecular radiobiology: the state of the art.
AB - Traditional cytotoxic agents used in cancer therapy were initially discovered
based on their ability to kill rapidly dividing cells. The targets of these early
generation agents were typically one or more aspects of DNA synthesis or mitosis.
Thus, dose-limiting toxicities commonly associated with these agents include GI
dysfunction, immunosuppression, and other consequences of injury to normal
tissues in which cells are replicating under normal physiologic conditions.
Although many of these agents still play an important role in cancer therapy when
given concurrently with radiation therapy, the major thrust of radiobiology
research in the last two decades has focused on discovering tumor-specific traits
that might be exploited for more selective targeting that would enhance the
efficacy of radiotherapy with less normal tissue toxicity. These newer generation
molecular targeted therapies interfere with the growth of tumor cells by
inhibiting genes and their protein products that are needed specifically by the
tumor for survival and expansion. These agents can be complementary to
radiotherapy, a spatially targeted agent. Although there have been extraordinary
technical advances in radiotherapy in recent years, we are reaching the limits of
improvements that radiotherapy delivery technology can bring and need different
approaches. This review will highlight promising new tumor biology-based targets
and other novel strategies to reduce normal tissue injury, increase tumor
control, and expand the use of radiotherapy to treat widespread metastatic
disease.
PMID- 25113769
TI - Nanotechnology in radiation oncology.
AB - Nanotechnology, the manipulation of matter on atomic and molecular scales, is a
relatively new branch of science. It has already made a significant impact on
clinical medicine, especially in oncology. Nanomaterial has several
characteristics that are ideal for oncology applications, including preferential
accumulation in tumors, low distribution in normal tissues, biodistribution,
pharmacokinetics, and clearance, that differ from those of small molecules.
Because these properties are also well suited for applications in radiation
oncology, nanomaterials have been used in many different areas of radiation
oncology for imaging and treatment planning, as well as for radiosensitization to
improve the therapeutic ratio. In this article, we review the unique properties
of nanomaterials that are favorable for oncology applications and examine the
various applications of nanotechnology in radiation oncology. We also discuss the
future directions of nanotechnology within the context of radiation oncology.
PMID- 25113770
TI - Interaction of radiation therapy with molecular targeted agents.
AB - The development of molecular targeted therapeutics in oncology builds on many
years of scientific investigation into the cellular mechanics of malignant
transformation and progression. The past two decades have brought an accelerating
pace to the clinical investigation of new molecular targeted agents, particularly
in the setting of metastatic disease. The integration of molecular targeted
agents into phase III clinical trial design has lagged in the curative treatment
setting, particularly in combination with established therapeutic modalities such
as radiation. In this review, we discuss the interaction of radiation and
molecular targeted therapeutics. The dynamics of cellular and tumor response to
radiation offer unique opportunities for beneficial interplay with molecular
targeted agents that may go unrecognized with conventional screening and
monotherapy clinical testing of novel agents. By using epidermal growth factor
receptor (EGFR) as a primary example, we discuss recent clinical studies that
illustrate the potential synergy of molecular targeted agents with radiation and
highlight the clinical value of such interactions. For various molecular targeted
agents, their greatest clinical impact may rest in combination with radiation,
and efforts to facilitate systematic investigation of this approach appear highly
warranted.
PMID- 25113774
TI - Radiation oncology: a snapshot in time, 2014.
PMID- 25113772
TI - Promise and pitfalls of heavy-particle therapy.
AB - Proton beam therapy, the most common form of heavy-particle radiation therapy, is
not a new invention, but it has gained considerable public attention because of
the high cost of installing and operating the rapidly increasing number of
treatment centers. This article reviews the physical properties of proton beam
therapy and focuses on the up-to-date clinical evidence comparing proton beam
therapy with the more standard and widely available radiation therapy treatment
alternatives. In a cost-conscious era of health care, the hypothetical benefits
of proton beam therapy will have to be supported by demonstrable clinical gains.
Proton beam therapy represents, through its scale and its cost, a battleground
for the policy debate around managing expensive technology in modern medicine.
PMID- 25113773
TI - Role of radiation therapy in palliative care of the patient with cancer.
AB - Radiotherapy is a successful, time-efficient, well-tolerated, and cost-effective
intervention that is crucial for the appropriate delivery of palliative oncology
care. The distinction between curative and palliative goals is blurred in many
patients with cancer, requiring that treatments be chosen on the basis of factors
related to the patient (ie, poor performance status, advanced age, significant
weight loss, severe comorbid disease), the cancer (ie, metastatic disease,
aggressive histology), or the treatment (ie, poor response to systemic therapy,
previous radiotherapy). Goals may include symptom relief at the site of primary
tumor or from metastatic lesions. Attention to a patient's discomfort and
transportation limitations requires hypofractionated courses, when feasible.
Innovative approaches include rapid response palliative care clinics as well as
the formation of palliative radiotherapy specialty services in academic centers.
Guidelines are providing better definitions of appropriate palliative
radiotherapy interventions, and bone metastases fractionation has become the
first radiotherapy quality measure accepted by the National Quality Forum.
Further advances in the palliative radiation oncology subspecialty will require
integration of education and training between the radiotherapy and palliative
care specialties.
PMID- 25113775
TI - Simultaneous determination of nine lignans from Schisandra chinensis extract
using ultra-performance liquid chromatography with tandem mass spectrometry in
rat plasma, urine, and gastrointestinal tract samples: application to the
pharmacokinetic study of Schisandra chinensis.
AB - The fruit of Schisandra chinensis is a well-known herbal medicine and dietary
supplement due to a variety of biological activities including antihepatotoxic
and antihyperlipidemic activities. However, the simultaneous validation
methodology and pharmacokinetic investigation of nine lignans of S. chinensis
extract in biological samples have not been proved yet. Thus, the present study
was undertaken to develop the proper sample preparation method and simultaneous
analytical method of schisandrol A, gomisin J, schisandrol B, tigloylgomisin H,
angeloylgomisin H, schisandrin A, schisandrin B, gomisin N, and schisandrin C in
the hexane-soluble extract of S. chinensis to apply for the pharmacokinetic study
in rats. All intra- and interprecisions of nine lignans were below 13.7% and
accuracies were 85.1-115% and it is enough to evaluate the pharmacokinetic
parameters after both intravenous and oral administration of hexane-soluble
extract of S. chinensis to rats.
PMID- 25113776
TI - Electrical resistivity behaviors of liquid Pb-Sn binary alloy in the presence of
ultrasonic field.
AB - Electrical resistivity behaviors of liquid Pb-Sn alloys have been investigated in
the presence of ultrasonic field. The process demonstrated significantly that
electrical resistivity could reveal the precise influence caused by ultrasound.
Details revealed by applying the resistivity measuring approach to the liquid Pb
Sn alloy show that the short ordered structures in the liquid could be modified
by ultrasonic irradiation, and the resistivity approach could have application
value in the ultrasonic irradiation process on the specific liquid metals and
alloys.
PMID- 25113771
TI - Role of imaging in the staging and response assessment of lymphoma: consensus of
the International Conference on Malignant Lymphomas Imaging Working Group.
AB - PURPOSE: Recent advances in imaging, use of prognostic indices, and molecular
profiling techniques have the potential to improve disease characterization and
outcomes in lymphoma. International trials are under way to test image-based
response-adapted treatment guided by early interim positron emission tomography
(PET)-computed tomography (CT). Progress in imaging is influencing trial design
and affecting clinical practice. In particular, a five-point scale to grade
response using PET-CT, which can be adapted to suit requirements for early- and
late-response assessment with good interobserver agreement, is becoming widely
used both in practice- and response-adapted trials. A workshop held at the 11th
International Conference on Malignant Lymphomas (ICML) in 2011 concluded that
revision to current staging and response criteria was timely. METHODS: An imaging
working group composed of representatives from major international cooperative
groups was asked to review the literature, share knowledge about research in
progress, and identify key areas for research pertaining to imaging and lymphoma.
RESULTS: A working paper was circulated for comment and presented at the Fourth
International Workshop on PET in Lymphoma in Menton, France, and the 12th ICML in
Lugano, Switzerland, to update the International Harmonisation Project guidance
regarding PET. Recommendations were made to optimize the use of PET-CT in staging
and response assessment of lymphoma, including qualitative and quantitative
methods. CONCLUSION: This article comprises the consensus reached to update
guidance on the use of PET-CT for staging and response assessment for
[18F]fluorodeoxyglucose-avid lymphomas in clinical practice and late-phase
trials.
PMID- 25113777
TI - N-methyl-trimethylacetamide in thin films displays infrared spectra of pi
helices, with visible static and dynamic growth phases, and then a beta-sheet.
AB - The simplest (minimal) peptide model is HCONHCH3. An increase in the pi-helix
content with increased substitution in the acyl portion suggested the examination
of N-methyl-trimethylacetamide) (NMT). NMT displays spectra, in which there is
evolution of a set of helices defined by their amide I maxima near 1686 (3(10)),
1655 (first pi), and, most importantly, at 1637 cm(-1) (pi). Expanded thin-film
infrared spectroscopy (XTFIS) shows pauses or slow stages, which are identified
as static phases followed by dynamic phases with the incremental gain or loss of
a helix turn. In addition, absorbance at 1637 cm(-1) suddenly increases at 82.1 s
(30% over 0.3 s), indicating a phase change and crystallization of the pi-helix,
along with a coincidental decrease in the absorbance for the first pi-helix. A
sharp peak occurs at the maximum of the phase change at 82.5 s, representing a
pure NMT pi-helix. The spectra then undergo a decreasing general absorption loss
over 150 s, with the pi-helix evolving further to an antiparallel beta-sheet
fragment. The spectral quality arises from the immobilization of polar molecules
on polar surfaces. The crystal structure is that of an antiparallel beta-sheet.
PMID- 25113778
TI - Co-inheritance of the rare beta hemoglobin variants Hb Yaounde, Hb Gorwihl and Hb
City of Hope with other alterations in globin genes: impact in genetic
counseling.
AB - PURPOSE: Nearly 1183 different molecular defects of the globin genes leading to
hemoglobin variants have been identified (http://globin.bx.psu.edu) over the past
decades. The purpose of this study was to report three cases, never described in
the literature, of co-inheritance of three beta hemoglobin variants with other
alterations in globin genes and to evaluate the clinical significance to conduct
an appropriate genetic counseling. PATIENTS AND METHODS: We report the molecular
study performed in three probands and their families, sampling during the
screening program conducted at the Laboratory for Molecular Prenatal Diagnosis of
Hemoglobinopathies at Villa Sofia-Cervello Hospital in Palermo, Italy. RESULTS:
This work allowed us to describe the co-inheritance of three rare beta hemoglobin
variants with other alterations in globin genes: the beta hemoglobin variant Hb
Yaounde [beta134(H12)Val>Ala], found for the first time in combination with
alphaalphaalpha(anti3.7) arrangement, and the beta hemoglobin variants Hb Gorwihl
[beta5(A2)Pro>Ala] and Hb City of Hope [beta69(E13)Gly>Ser], found both in
association with beta(0) -thalassemia. CONCLUSION: The present work emphasizes
the importance of a careful evaluation of the hematological data, especially in
cases of atypical hematological parameters, to carry out an adequate and complete
molecular study and to formulate an appropriate genetic counseling for couples at
risk.
PMID- 25113779
TI - Scientific and technical data sharing: a trading perspective.
AB - It is arguably a precept that the open sharing of data maximises the scientific
utility of the research that generated that data. Indeed, progress depends on
individual scientists being able to build on the results produced by others. The
means to facilitate sharing undoubtedly exist, but various studies have
identified reluctance among researchers to share information with their peers, at
least until the professional priorities of the original researchers have been
accommodated. With a view to encouraging less inhibited collaboration, we
appraise the processes of data exchange from the perspective of a trading
environment and consider how data exchanges might promote (or perhaps hinder)
collaboration in data-rich scientific research disciplines and how such an
exchange might be set up. We suggest an exchange with trusted brokers (akin to
the commodity markets) as a way to overcome the challenges of the current
environment. We conclude by encouraging the scientific and technical community to
debate the merits of a trading perspective on data sharing and exchange.
PMID- 25113782
TI - Doctor, what does my knee arthroplasty weigh?
AB - The aim of this study was to compare the weight of the total knee arthroplasty
(TKA) implants and the weight of the natural knee. A prospective study was
conducted with two different brands of cemented primary TKA. During the
procedure, we collected the removed bone, soft tissues and the post-implantation
cement and weighed them all separately at the end. In both groups, the implants
plus cement were significantly heavier than the removed bone and soft tissues.
The average weight gained was 266.7 +/- 35.1 g for group 1 and 279.1 +/- 48.7 g
for group 2. This significant local weight gained after TKA is a new parameter
that should be taken into account for further studies and when creating new
implants.
PMID- 25113781
TI - Cardiorespiratory responses to 6-minute walk test in interstitial lung disease:
not always a submaximal test.
AB - BACKGROUND: The 6-minute walk test (6 MWT) is used to measure exercise capacity
and assess prognosis in interstitial lung disease (ILD). Although the 6 MWT is
usually considered to be a test of submaximal exercise capacity in ILD, the
physiological load imposed by this test is not well described and 6 MWT outcomes
are poorly understood. This study aimed to compare cardiorespiratory responses to
6 MWT and cardiopulmonary exercise test (CPET) in people with ILD. METHODS: 47
participants with ILD (27 idiopathic pulmonary fibrosis (IPF), mean age 71 (SD
12) years, diffusing capacity for carbon monoxide (TLCO) 49(15) %predicted)
undertook CPET and 6 MWT on the same day in random order. Oxygen uptake (VO(2)),
ventilation (VE) and carbon dioxide production (VCO2) were assessed during each
test using a portable metabolic cart. RESULTS: The VO(2)peak during the 6 MWT was
lower than during CPET (1.17(0.27) vs 1.30(0.37) L.min-1, p = 0.001),
representing an average of 94% (range 62-135%) of CPET VO(2)peak. Achieving a
higher percentage of CPET VO(2)peak on 6 MWT was associated with lower TLCO
%predicted (r = -0.43, p = 0.003) and more desaturation during walking (r =
0.46, p = 0.01). The VEpeak and VCO(2)peak were significantly lower during 6 MWT
than CPET (p < 0.05). However, participants desaturated more during the 6 MWT
(86(6)% vs 89(4)%, p < 0.001). The degree of desaturation was not affected by the
percent of peak VO2 achieved during the 6 MWT. Responses were similar in the
subgroup with IPF. CONCLUSIONS: On average, the 6 MWT elicits a high but
submaximal oxygen uptake in people with ILD. However the physiological load
varies between individuals, with higher peak VO2 in those with more severe
disease that may match or exceed that achieved on CPET. The 6 MWT is not always a
test of submaximal exercise capacity in people with ILD.
PMID- 25113783
TI - Patient-related predictors of treatment failure after primary total knee
arthroplasty for osteoarthritis.
AB - The aim was to identify patient-related predictors of treatment failure after
primary total knee arthroplasty for osteoarthritis. Treatment failure included
surgical revision or clinical failure, which was defined by less than 70 in any
score of the Knee Society. Prospective follow-up was performed in 412 consecutive
patients with a minimum of 5 years. Multivariate logistic regression analysis
revealed that higher Charlson index, worse preoperative Knee Society function,
and Western Ontario McMaster University pain component were significantly
associated with treatment failure. This study identified clinically important
patient-related predictors of treatment failure after TKA, which may be useful
preoperatively in identifying patients with risk of failure.
PMID- 25113784
TI - Prevalence and predictors of post-operative coronal alignment outliers and their
association with the functional outcomes in navigated total knee arthroplasty.
AB - We aimed to determine the prevalence and predictors for being an outlier after
navigated TKA and asked whether navigated TKAs with perfect coronal alignment
have better functional outcomes than those without it. Alignment was measured in
124 patients (191 knees) with navigated TKAs who were available for 1year
functional outcome assessment. The outcomes were compared among the 3 subgroups
divided by the deviation of mechanical axis from neutral (0 degrees ): the
perfect, 0 degrees or within 1 degrees ; the acceptable, 1 degrees -3 degrees ;
and the outlier, beyond 3 degrees . The prevalence of outliers was 20.4%, and the
severity of preoperative varus deformity was the strongest predictor. Accuracy of
coronal alignment in radiographs did not correlate consistently with functional
outcomes.
PMID- 25113785
TI - Cell blocks in cytopathology: a review of preparative methods, utility in
diagnosis and role in ancillary studies.
AB - The cell block (CB) is a routine procedure in cytopathology that has gained
importance because of its pivotal role in diagnosis and ancillary studies. There
is no precise review in the published literature that deals with the various
methods of preparation of CB, its utility in diagnosis, immunocytochemistry (ICC)
or molecular testing, and its drawbacks. An extensive literature search on CB in
cytology using internet search engines was performed for this review employing
the following keywords: cell block, cytoblock, cytology, cytopathology, methods,
preparation, fixatives, diagnostic yield, ancillary and molecular studies. Ever
since its introduction more than a century ago, the CB technique has undergone
numerous modifications to improve the quality of the procedure; however, the
overall principle remains the same in each method. CBs can be prepared from
virtually all varieties of cytological samples. In today's era of personalized
medicine, cytological specimens, including CBs, augment the utility of
cytological samples in analysing the molecular alterations as effectively as
surgical biopsies or resection specimens. With the availability of molecular
targeted therapy for many cancers, a large number of recent studies have used
cytological material or CBs for molecular characterization. The various
techniques of CB preparation with different fixatives, their advantages and
limitations, and issues of diagnostic yield are discussed in this review.
PMID- 25113786
TI - Comparative effects of biological and chemical dispersants on the bioavailability
and toxicity of crude oil to early life stages of marine medaka (Oryzias
melastigma).
AB - The authors assessed the bioavailability and chronic toxicity of water
accommodated fractions of crude oil (WAFs) and 2 dispersants plus dispersed crude
oil (chemical dispersant + crude oil [CE-WAF] and biological dispersant + crude
oil [BE-WAF]) on the early life stages of marine medaka, Oryzias melastigma. The
results showed that the addition of the 2 dispersants caused a 3- and 4-fold
increase in concentrations of summed priority polycyclic aromatic hydrocarbons
(PAHs) and high-molecular-weight PAHs with 3 or more benzene rings. The chemical
and biological dispersants increased the bioavailability (as measured by
ethoxyresorufin-O-dethylase activity) of crude oil 6-fold and 3-fold,
respectively. Based on nominal concentrations, chronic toxicity (as measured by
deformity) in WAFs exhibited a 10-fold increase in CE-WAF and a 3-fold increase
in BE-WAF, respectively. When total petroleum hydrocarbon was measured, the
differences between WAF and CE-WAF treatments disappeared, and CE-WAF was
approximately 10 times more toxic than BE-WAF. Compared with the chemical
dispersant, the biological dispersant possibly modified the toxicity of oil
hydrocarbons because of the increase in the proportion of 2- and 3-ringed PAHs in
water. The chemical and biological dispersants enhanced short-term
bioaccumulation and toxicity, through different mechanisms. These properties
should be considered in addition to their efficacy in degrading oil when oil
spill management strategies are selected.
PMID- 25113787
TI - Two novel mutations in conserved codons indicate that CHCHD10 is a gene
associated with motor neuron disease.
PMID- 25113788
TI - Reply: Two novel mutations in conserved codons indicate that CHCHD10 is a gene
associated with motor neuron disease.
PMID- 25113789
TI - The evolution of primary progressive apraxia of speech.
AB - Primary progressive apraxia of speech is a recently described neurodegenerative
disorder in which patients present with an isolated apraxia of speech and show
focal degeneration of superior premotor cortex. Little is known about how these
individuals progress over time, making it difficult to provide prognostic
estimates. Thirteen subjects with primary progressive apraxia of speech underwent
two serial comprehensive clinical and neuroimaging evaluations 2.4 years apart
[median age of onset = 67 years (range: 49-76), seven females]. All underwent
detailed speech and language, neurological and neuropsychological assessments,
and magnetic resonance imaging, diffusion tensor imaging and (18)F
fluorodeoxyglucose positron emission tomography at both baseline and follow-up.
Rates of change of whole brain, ventricle, and midbrain volumes were calculated
using the boundary-shift integral and atlas-based parcellation, and rates of
regional grey matter atrophy were assessed using tensor-based morphometry. White
matter tract degeneration was assessed on diffusion-tensor imaging at each time
point. Patterns of hypometabolism were assessed at the single subject-level.
Neuroimaging findings were compared with a cohort of 20 age, gender, and scan
interval matched healthy controls. All subjects developed extrapyramidal signs.
In eight subjects the apraxia of speech remained the predominant feature. In the
other five there was a striking progression of symptoms that had evolved into a
progressive supranuclear palsy-like syndrome; they showed a combination of severe
parkinsonism, near mutism, dysphagia with choking, vertical supranuclear gaze
palsy or slowing, balance difficulties with falls and urinary incontinence, and
one was wheelchair bound. Rates of whole brain atrophy (1.5% per year; controls =
0.4% per year), ventricular expansion (8.0% per year; controls = 3.3% per year)
and midbrain atrophy (1.5% per year; controls = 0.1% per year) were elevated (P
<= 0.001) in all 13, compared to controls. Increased rates of brain atrophy over
time were observed throughout the premotor cortex, as well as prefrontal cortex,
motor cortex, basal ganglia and midbrain, while white matter tract degeneration
spread into the splenium of the corpus callosum and motor cortex white matter.
Hypometabolism progressed over time in almost all subjects. These findings
demonstrate that some subjects with primary progressive apraxia of speech will
rapidly evolve and develop a devastating progressive supranuclear palsy-like
syndrome ~ 5 years after onset, perhaps related to progressive involvement of
neocortex, basal ganglia and midbrain. These findings help improve our
understanding of primary progressive apraxia of speech and provide some important
prognostic guidelines.
PMID- 25113791
TI - A novel CDC73 gene mutation in an Italian family with hyperparathyroidism-jaw
tumour (HPT-JT) syndrome.
AB - PURPOSE: The CDC73 gene, encoding parafibromin, has been identified as a tumour
suppressor gene both in hyperparathyroidism-jaw tumour (HPT-JT) syndrome and in
sporadic parathyroid carcinoma. While the vast majority of CDC73 mutations affect
the N-terminus or the central core of the encoded protein, as yet few mutations
have been reported affecting the C-terminus. Here, we report a case (Caucasian
female, 28 years) with an invasive ossifying fibroma of the left mandible and
hyperparathyroidism (sCa = 16 mg/dl, PTH = 660 pg/mL) due to a parathyroid lesion
of 20 mm, hystologically diagnosed as carcinoma. METHODS: The whole CDC73 gene
was screened for the presence of mutations by Sanger sequencing.
Immunohistochemistry, in vitro functional assays, Western blotting, MTT assays
and in-silico modelling were performed to assess the effect of the detected
mutation. RESULTS: Sequence analysis of the CDC73 gene in the proband revealed
the presence of a novel deletion affecting the C-terminus of the encoded protein
(c.1379delT/p.L460Lfs*18). Clinical and genetic analyses of the available
relatives led to the identification of three additional carriers, one of whom was
also affected by a parathyroid lesion. Immunohistochemistry, Western blotting,
MTT and in-silico modelling assays revealed that the deletion leads to down
regulation of the mutated protein, most likely through a proteasome-mediated
pathway. We also found that the deletion may cause a conformational change in the
C-terminus of the protein, possibly affecting its interaction with partner
proteins. Finally, we found that the mutant protein enhances cellular growth.
CONCLUSIONS: We report a novel mutation in the CDC73 gene that may underlie HPT
JT syndrome. This mutation appears to affect the C-terminal moiety of the encoded
protein, which is thought to interact with other protein partners. The
identification of these partners may be instrumental for our understanding of the
CDC73-associated phenotype.
PMID- 25113792
TI - Sinoatrial node dysfunction induces cardiac arrhythmias in diabetic mice.
AB - BACKGROUND: The aim of this study was to probe cardiac complications, including
heart-rate control, in a mouse model of type-2 diabetes. Heart-rate development
in diabetic patients is not straight forward: In general, patients with diabetes
have faster heart rates compared to non-diabetic individuals, yet diabetic
patients are frequently found among patients treated for slow heart rates. Hence,
we hypothesized that sinoatrial node (SAN) dysfunction could contribute to our
understanding of the mechanism behind this conundrum and the consequences
thereof. METHODS: Cardiac hemodynamic and electrophysiological characteristics
were investigated in diabetic db/db and control db/+ mice. RESULTS: We found
improved contractile function and impaired filling dynamics of the heart in db/db
mice, relative to db/+ controls. Electrophysiologically, we observed comparable
heart rates in the two mouse groups, but SAN recovery time was prolonged in
diabetic mice. Adrenoreceptor stimulation increased heart rate in all mice and
elicited cardiac arrhythmias in db/db mice only. The arrhythmias emanated from
the SAN and were characterized by large RR fluctuations. Moreover, nerve density
was reduced in the SAN region. CONCLUSIONS: Enhanced systolic function and
reduced diastolic function indicates early ventricular remodeling in obese and
diabetic mice. They have SAN dysfunction, and adrenoreceptor stimulation triggers
cardiac arrhythmia originating in the SAN. Thus, dysfunction of the intrinsic
cardiac pacemaker and remodeling of the autonomic nervous system may conspire to
increase cardiac mortality in diabetic patients.
PMID- 25113795
TI - Contactless conductivity detection for analytical techniques-developments from
2012 to 2014.
AB - The review covers the progress of capacitively coupled contactless conductivity
detection over the 2 years leading up to mid-2014. During this period many new
applications for conventional CE as well as for microchip separation devices have
been reported; prominent areas have been clinical, pharmaceutical, forensic, and
food analyses. Further progress has been made in the development of field
portable instrumentation based on CE with contactless conductivity detection.
Several reports concern the combination with sample pretreatment techniques, in
particular electrodriven extractions. Accounts of arrays of contactless
conductivity detectors have appeared, which have been created for quite different
tasks requiring spatially resolved information. The trend of the use of
contactless conductivity measurements for applications other than CE has
continued.
PMID- 25113794
TI - 7T T2*-weighted magnetic resonance imaging reveals cortical phase differences
between early- and late-onset Alzheimer's disease.
AB - The aim of this study is to explore regional iron-related differences in the
cerebral cortex, indicative of Alzheimer's disease pathology, between early- and
late-onset Alzheimer's disease (EOAD, LOAD, respectively) patients using 7T
magnetic resonance phase images. High-resolution T2(*)-weighted scans were
acquired in 12 EOAD patients and 17 LOAD patients with mild to moderate disease
and 27 healthy elderly control subjects. Lobar peak-to-peak phase shifts and
regional mean phase contrasts were computed. An increased peak-to-peak phase
shift was found for all lobar regions in EOAD patients compared with LOAD
patients (p < 0.05). Regional mean phase contrast in EOAD patients was higher
than in LOAD patients in the superior medial and middle frontal gyrus, anterior
and middle cingulate gyrus, postcentral gyrus, superior and inferior parietal
gyrus, and precuneus (p <= 0.042). These data suggest that EOAD patients have an
increased iron accumulation, possibly related to an increased amyloid deposition,
in specific cortical regions as compared with LOAD patients.
PMID- 25113796
TI - Beta-blockers in cirrhosis and refractory ascites: a retrospective cohort study
and review of the literature.
AB - OBJECTIVE: It is currently discussed if beta-blockers exert harmful effects and
increase mortality in patients with cirrhosis and refractory ascites. In this
study, we provide an overview of the available literature in this field in
combination with a retrospective analysis of 61 patients with cirrhosis and
refractory ascites in a tertiary unit. MATERIAL AND METHODS: We performed a
systematic search of literature in May 2014. In addition, 61 patients with
cirrhosis and ascites were identified and followed from development of refractory
ascites until death or end of follow-up. RESULTS: Fourteen trials (9 trials on
propranolol, 1 case-control study and 4 retrospective analyses) were identified.
One trial suggested an increased mortality in patients treated with beta-blockers
and refractory ascites. The results of the remaining trials were inconclusive. No
increase in mortality among beta-blocker-treated patients was found in the
present retrospective analysis. CONCLUSIONS: Treatment with beta-blockers may
increase mortality in patients with cirrhosis and refractory ascites. However,
the current evidence is sparse and high-quality studies are warranted to clarify
the matter.
PMID- 25113790
TI - Long non-coding RNAs in cancer: implications for personalized therapy.
AB - Long non-coding RNAs (lncRNAs, pseudogenes and circRNAs) have recently come into
light as powerful players in cancer pathogenesis and it is becoming increasingly
clear that they have the potential of greatly contributing to the spread and
success of personalized cancer medicine. In this concise review, we briefly
introduce these three classes of long non-coding RNAs. We then discuss their
applications as diagnostic and prognostic biomarkers. Finally, we describe their
appeal as targets and as drugs, while pointing out the limitations that still lie
ahead of their definitive entry into clinical practice.
PMID- 25113797
TI - Impact of implementation of the Surgical Care Improvement Project and future
strategies for improving quality in surgery.
AB - BACKGROUND: We present a comprehensive systematic review of the effect of
Surgical Care Improvement Project (SCIP) measures on surgical site infections
(SSIs) as related to SCIP compliance. DATA SOURCES: A systematic review of the
peer-reviewed literature was performed on PubMed, Medline, and Cochrane database
group using their own search engines. Keywords used were Surgical Care
Improvement Project (SCIP), adherence, compliance, surgical site infection (SSI),
infection bundle, antibiotics, perioperative antibiotics, and combinations
thereof. Furthermore, reference lists of selected articles were cross-searched
for additional literature. Papers published from January 1, 1998 to January 1,
2014 were included. RESULTS: A comprehensive analysis of these data demonstrated
an 18% decrease in the odds of developing SSI and a cumulative 4% decrease in
SSI. The largest increases in compliance for individual SCIP measures were
reported between 2004 and 2006. However, compliance with multiple measures
simultaneously had the sharpest increase between 2006 and 2009 without a
definitive asymptote ascertained from the current data. CONCLUSIONS: These
results represent some positive progress toward the SCIP task force's 2006 goal
of a 25% decrease in SSI by 2010. Suggestions for improved future papers in this
area were also added.
PMID- 25113793
TI - Relationships between default-mode network connectivity, medial temporal lobe
structure, and age-related memory deficits.
AB - Advanced aging negatively impacts memory performance. Brain aging has been
associated with shrinkage in medial temporal lobe structures essential for memory
-including hippocampus and entorhinal cortex--and with deficits in default-mode
network connectivity. Yet, whether and how these imaging markers are relevant to
age-related memory deficits remains a topic of debate. Using a sample of 182
older (age 74.6 +/- 6.2 years) and 66 young (age 22.2 +/- 3.6 years)
participants, this study examined relationships among memory performance,
hippocampus volume, entorhinal cortex thickness, and default-mode network
connectivity across aging. All imaging markers and memory were significantly
different between young and older groups. Each imaging marker significantly
mediated the relationship between age and memory performance and collectively
accounted for most of the variance in age-related memory performance. Within
older participants, default-mode connectivity and hippocampus volume were
independently associated with memory. Structural equation modeling of cross
sectional data within older participants suggest that entorhinal thinning may
occur before reduced default-mode connectivity and hippocampal volume loss, which
in turn lead to deficits in memory performance.
PMID- 25113799
TI - Embryonic aneuploidy: overcoming molecular genetics challenges improves outcomes
and changes practice patterns.
AB - Since its inception, in vitro fertilization (IVF) has pursued molecular
technology to improve patient outcomes, leading to enhanced methods of embryo
selection. Comprehensive chromosomal screening (CCS) is a powerful tool that
decreases maternal and neonatal morbidity due to multiple gestations by allowing
the transfer of fewer embryos while maintaining success rates. To optimize this
genetic test, physiological principles limiting the timing and type of cells to
be removed had to be realized. Molecular barriers involved in genome
amplification and ensuring the accuracy and validity of the CCS platform required
a multistep approach to ensure that this technology was not used prematurely.
Only after ensuring that the potential for harm was minimized and benefit
maximized could clinicians use this technology to improve patient care.
PMID- 25113800
TI - Evaluation of tumor response to cytokine-induced killer cells therapy in
malignant solid tumors.
AB - CIK cells therapy has been evaluated as an adoptive cell immunotherapy for cancer
patients, but there still have not been any standardized systems for evaluating
the antitumor efficacy yet. The WHO and RECIST criteria have already been
established for a few years but not sufficient to fully characterize the activity
of immunotherapy. Based on these two criteria, the irRC was proposed for
evaluating the efficacy of immunotherapy. A variety of bioassays for immune
monitoring including the specific and non-specific methods, have been
established. We recommend detect levels of various immunocytes, immune molecules
and soluble molecules to find the correlations among them and clinicopathological
characteristics to establish criteria for immunological classification. We also
recommend a paradigm shift for the oncologists in the evaluation of immune
therapies to ensure assessment of activity based on clinically relevant criteria
and time points.
PMID- 25113802
TI - Carcinoid tumor of the minor duodenal papilla: a rare entity in elderly
individuals.
PMID- 25113803
TI - High-capacity anode materials for sodium-ion batteries.
AB - Na-ion batteries are an attractive alternative to Li-ion batteries for large
scale energy storage systems because of their low cost and the abundant Na
resources. This Review provides a comprehensive overview of selected anode
materials with high reversible capacities that can increase the energy density of
Na-ion batteries. Moreover, we discuss the reaction and failure mechanisms of
those anode materials with a view to suggesting promising strategies for
improving their electrochemical performance.
PMID- 25113805
TI - Different regions of bovine deep digital flexor tendon exhibit distinct elastic,
but not viscous, mechanical properties under both compression and shear loading.
AB - Tendons in different locations function in unique, and at times complex, in vivo
loading environments. Specifically, some tendons are subjected to compression,
shear and/or torsion in addition to tensile loading, which play an important role
in regulating tendon properties. To date, there have been few studies evaluating
tendon mechanics when loaded in compression and shear, which are particularly
relevant for understanding tendon regions that experience such non-tensile
loading during normal physiologic function. The objective of this study was to
evaluate mechanical responses of different regions of bovine deep digital flexor
tendons (DDFT) under compressive and shear loading, and correlate structural
characteristics to functional mechanical properties. Distal and proximal regions
of DDFT were evaluated in a custom-made loading system via three-step incremental
stress-relaxation tests. A two-relaxation-time solid linear model was used to
describe the viscoelastic response. Results showed large differences in the
elastic behavior between regions: distal region stresses were 4-5 times larger
than proximal region stresses during compression and 2-3 times larger during
shear. Surprisingly, the viscous (i.e., relaxation) behavior was not different
between regions for either compression or shear. Histological analysis showed
that collagen and proteoglycan in the distal region distributed differently from
the proximal region. Results demonstrate mechanical differences between two
regions of DDFT under compression and shear loading, which are attributed to
variations of composition and microstructural organization. These findings deepen
our understanding of structure-function relationships of tendon, particularly for
tissues adapted to supporting combinations of tension, compression, and shear in
physiological loading environments.
PMID- 25113804
TI - Docetaxel followed by abiraterone in metastatic castration-resistant prostate
cancer: efficacy and predictive parameters in a large single center cohort.
AB - PURPOSE: To report the outcome and course of disease in patients with metastatic
castration-resistant prostate cancer (mCRPC) treated with first-line docetaxel
followed by abiraterone acetate in a single center. METHODS: In this
retrospective observational study, we reviewed the course of disease of all
applicable patients with mCRPC treated with docetaxel followed by abiraterone at
our center. We analyzed progression-free survival (PFS) of docetaxel and
abiraterone treatments. We further searched for predictive factors for the
duration of treatment response. RESULTS: Median PFS between initiation of
androgen deprivation therapy and the diagnosis of mCRPC was 32 months. Median PFS
on docetaxel treatment was 9 months. Median PFS on abiraterone treatment was 11
months. Patients with higher Gleason scores (GS) (8-10) at initial diagnosis had
a significantly longer median PFS on docetaxel as compared to patients with GS 6
7, p = 0.01. We demonstrate a significant correlation between the PFS on
docetaxel and PFS on abiraterone in the post-docetaxel setting (Kendall tau r =
0.32, p = 0.019) as well as a significant negative correlation between the PSA
nadir under abiraterone treatment and the time to progression under abiraterone
(Kendall tau r = -0.43, p = 0.007). CONCLUSIONS: High Gleason score appears to be
predictive of duration of response to docetaxel. Interestingly, progression-free
survival with abiraterone appears to be correlated with the duration of response
with docetaxel, whereas PSA decline and low nadir appear to be predictive of
response to abiraterone.
PMID- 25113806
TI - About the inevitable compromise between spatial resolution and accuracy of strain
measurement for bone tissue: a 3D zero-strain study.
AB - The accurate measurement of local strain is necessary to study bone mechanics and
to validate micro computed tomography (uCT) based finite element (FE) models at
the tissue scale. Digital volume correlation (DVC) has been used to provide a
volumetric estimation of local strain in trabecular bone sample with a reasonable
accuracy. However, nothing has been reported so far for uCT based analysis of
cortical bone. The goal of this study was to evaluate accuracy and precision of a
deformable registration method for prediction of local zero-strains in bovine
cortical and trabecular bone samples. The accuracy and precision were analyzed by
comparing scans virtually displaced, repeated scans without any repositioning of
the sample in the scanner and repeated scans with repositioning of the samples.
The analysis showed that both precision and accuracy errors decrease with
increasing the size of the region analyzed, by following power laws. The main
source of error was found to be the intrinsic noise of the images compared to the
others investigated. The results, once extrapolated for larger regions of
interest that are typically used in the literature, were in most cases better
than the ones previously reported. For a nodal spacing equal to 50 voxels (498
um), the accuracy and precision ranges were 425-692 uepsilon and 202-394
uepsilon, respectively. In conclusion, it was shown that the proposed method can
be used to study the local deformation of cortical and trabecular bone loaded
beyond yield, if a sufficiently high nodal spacing is used.
PMID- 25113801
TI - Impact of tissue-specific stem cells on lineage-specific differentiation: a focus
on the musculoskeletal system.
AB - Tissue-specific stem cells are found throughout the body and, with proper
intervention and environmental cues, these stem cells exercise their capabilities
for differentiation into several lineages to form cartilage, bone, muscle, and
adipose tissue in vitro and in vivo. Interestingly, it has been widely
demonstrated that they do not differentiate with the same efficacy during lineage
specific differentiation studies, as the tissue-specific stem cells are generally
more effective when differentiating toward the tissues from which they were
derived. This review focuses on four mesodermal lineages for tissue-specific stem
cell differentiation: adipogenesis, chondrogenesis, myogenesis, and osteogenesis.
It is intended to give insight into current multilineage differentiation and
comparative research, highlight and contrast known trends regarding
differentiation, and introduce supporting evidence which demonstrates particular
tissue-specific stem cells' superiority in lineage-specific differentiation,
along with their resident tissue origins and natural roles. In addition, some
epigenetic and transcriptomic differences between stem cells which may explain
the observed trends are discussed.
PMID- 25113807
TI - The role of transmembrane proteins on force transmission in skeletal muscle.
AB - Lateral transmission of force from myofibers laterally to the surrounding
extracellular matrix (ECM) via the transmembrane proteins between them is
impaired in old muscles. Changes in geometrical and mechanical properties of ECM
of skeletal muscle do not fully explain the impaired lateral transmission with
aging. The objective of this study was to determine the role of transmembrane
proteins on force transmission in skeletal muscle. In this study, a 2D finite
element model of single muscle fiber composed of myofiber, ECM, and the
transmembrane proteins between them was developed to determine how changes in
spatial density and mechanical properties of transmembrane proteins affect the
force transmission in skeletal muscle. We found that force transmission and
stress distribution are not affected by mechanical stiffness of the transmembrane
proteins due to its non-linear stress-strain relationship. Results also showed
that the muscle fiber with insufficient transmembrane proteins near the end of
muscle fiber transmitted less force than that with more proteins does. Higher
stress was observed in myofiber, ECM, and proteins in the muscle fiber with fewer
proteins.
PMID- 25113808
TI - 3D finite element model of the diabetic neuropathic foot: a gait analysis driven
approach.
AB - Diabetic foot is an invalidating complication of diabetes that can lead to foot
ulcers. Three-dimensional (3D) finite element analysis (FEA) allows
characterizing the loads developed in the different anatomical structures of the
foot in dynamic conditions. The aim of this study was to develop a subject
specific 3D foot FE model (FEM) of a diabetic neuropathic (DNS) and a healthy
(HS) subject, whose subject specificity can be found in term of foot geometry and
boundary conditions. Kinematics, kinetics and plantar pressure (PP) data were
extracted from the gait analysis trials of the two subjects with this purpose.
The FEM were developed segmenting bones, cartilage and skin from MRI and drawing
a horizontal plate as ground support. Materials properties were adopted from
previous literature. FE simulations were run with the kinematics and kinetics
data of four different phases of the stance phase of gait (heel strike, loading
response, midstance and push off). FEMs were then driven by group gait data of 10
neuropathic and 10 healthy subjects. Model validation focused on agreement
between FEM-simulated and experimental PP. The peak values and the total
distribution of the pressures were compared for this purpose. Results showed that
the models were less robust when driven from group data and underestimated the PP
in each foot subarea. In particular in the case of the neuropathic subject's
model the mean errors between experimental and simulated data were around the 20%
of the peak values. This knowledge is crucial in understanding the aetiology of
diabetic foot.
PMID- 25113809
TI - Regarding: Udeh BL, et al. The 2-year Cost-effectiveness of 3 Options to Treat
Lumbar Spinal Stenosis Patients. Pain Pract 2014 Jan 3 [epub ahead of print].
PMID- 25113810
TI - Relationship of CD146 expression to secretion of interleukin (IL)-17, IL-22 and
interferon-gamma by CD4(+) T cells in patients with inflammatory arthritis.
AB - Expression of the adhesion molecule, CD146/MCAM/MelCAM, on T cells has been
associated with recent activation, memory subsets and T helper type 17 (Th17)
effector function, and is elevated in inflammatory arthritis. Th17 cells have
been implicated in the pathogenesis of rheumatoid arthritis (RA) and
spondyloarthritides (SpA). Here, we compared the expression of CD146 on CD4(+) T
cells between healthy donors (HD) and patients with RA and SpA [ankylosing
spondylitis (AS) or psoriatic arthritis (PsA)] and examined correlations with
surface markers and cytokine secretion. Peripheral blood mononuclear cells (PBMC)
were obtained from patients and controls, and synovial fluid mononuclear cells
(SFMC) from patients. Cytokine production [elicited by phorbol myristate acetate
(PMA)/ionomycin] and surface phenotypes were evaluated by flow cytometry.
CD146(+) CD4(+) and interleukin (IL)-17(+) CD4(+) T cell frequencies were
increased in PBMC of PsA patients, compared with HD, and in SFMC compared with
PBMC. CD146(+) CD4(+) T cells were enriched for secretion of IL-17 [alone or with
IL-22 or interferon (IFN)-gamma] and for some putative Th17-associated surface
markers (CD161 and CCR6), but not others (CD26 and IL-23 receptor). CD4(+) T
cells producing IL-22 or IFN-gamma without IL-17 were also present in the
CD146(+) subset, although their enrichment was less marked. Moreover, a majority
of cells secreting these cytokines lacked CD146. Thus, CD146 is not a sensitive
or specific marker of Th17 cells, but rather correlates with heterogeneous
cytokine secretion by subsets of CD4(+) helper T cells.
PMID- 25113812
TI - Using a thermoluminescent dosimeter to evaluate the location reliability of the
highest-skin dose area detected by treatment planning in radiotherapy for breast
cancer.
AB - Acute skin reaction during adjuvant radiotherapy for breast cancer is an
inevitable process, and its severity is related to the skin dose. A high-skin
dose area can be speculated based on the isodose distribution shown on a
treatment planning. To determine whether treatment planning can reflect high-skin
dose location, 80 patients were collected and their skin doses in different areas
were measured using a thermoluminescent dosimeter to locate the highest-skin dose
area in each patient. We determined whether the skin dose is consistent with the
highest-dose area estimated by the treatment planning of the same patient. The
chi(2) and Fisher exact tests revealed that these 2 methods yielded more
consistent results when the highest-dose spots were located in the axillary and
breast areas but not in the inframammary area. We suggest that skin doses shown
on the treatment planning might be a reliable and simple alternative method for
estimating the highest skin doses in some areas.
PMID- 25113813
TI - Dosimetric comparison of intensity-modulated solutions for intact prostate
cancer.
AB - The purpose of this study is intended to investigate the implementation of a
modified class solution for intact prostate intensity-modulated radiation therapy
(IMRT). The class solution uses 2 additional optimization structures intended to
increase target conformity and decrease unnecessary dose to healthy tissue. A
total of 10 randomly selected intact prostate IMRT patients were chosen for this
retrospective study. Each of the original IMRT plans was compared with a modified
class solution. The class solution implemented 2 additional optimization
structures. The 95_OPT was intended to increase target conformity, and the
Avoidance_3780 was intended to reduce normal tissue. Each plan was evaluated for
minimum, maximum, and mean doses to the target. Additionally, mean normal tissue
dose, total monitor units (MUs), and segments were investigated. Conformity index
and normal healthy index were also compared. All comparisons were evaluated using
a paired t-test using GraphPad software. Evaluations of MUs; segments; minimum,
maximum, mean target doses; mean normal tissue dose; and conformity index did not
demonstrate a significant difference between the modified class solution and the
original plans. However, evaluation of healthy tissue conformity index indicated
a significant difference. Overall, 70% of the original plans failed to
demonstrate a satisfactory score (< 0.6) of properly sparing normal healthy
tissue, whereas 70% of the modified plans exhibited a satisfactory score (> 0.6).
Most (90%) of the modified plans demonstrated a greater number of segments than
the compared original plan. A modified class solution provides a good starting
point for planning intact prostate cancer. The addition of the Avoidance_3780
structure increases the healthy tissue conformity index score.
PMID- 25113814
TI - Effect of local heating on postprandial blood glucose excursions using the
InsuPad device: results of an outpatient crossover study.
AB - The InsuPad is a medical device to accelerate insulin resorption by applying
local heat at the insulin injection site. This crossover study examined the
impact of the InsuPad use on postprandial glucose excursions under daily life
conditions. In 1 study phase, diabetic patients used the InsuPad when injecting
bolus insulin before breakfast and dinner and measured their blood glucose 5
times daily (before breakfast, lunch, and dinner and after breakfast and dinner).
In the other study phase, blood glucose measurements were maintained without
using the InsuPad. The order of the study phases was randomized. Twenty patients
with a high insulin demand took part (30% type 1 diabetes, age 53.7 +/- 8.9
years, diabetes duration 14.9 +/- 7.4 years; HbA1c 8.3 +/- 0.8%; total daily
insulin demand 0.97 +/- 0.32 IU per kg). Postprandial glucose excursion was
reduced by 15.4 mg/dl (95% CI 9.7-21.2 mg/dl; P = .011) after breakfast and
dinner if InsuPad was used. The mean blood glucose was lower by 8.8 mg/dl (95% CI
0:3-18:0 mg/dl; P = .099) when using the InsuPad. Safety parameters and the
percentage of hypoglycemic (< 60 mg/dl) or hyperglycemic (> 300 mg/dl) blood
glucose measurements were not negatively affected by InsuPad use (hypoglycemic
values 1.4% vs 1.5%, P = .961; hyperglycemic values 2.6% vs 4.0%, P = .098).
Local heating of the insulin injection site by use of the InsuPad device is an
effective and safe method to reduce postprandial blood glucose excursions under
daily life conditions without negative side effects on the occurrence of low or
high blood glucose values.
PMID- 25113815
TI - Nitric oxide reactivity of [2Fe-2S] clusters leading to H2S generation.
AB - The crosstalk between two biologically important signaling molecules, nitric
oxide (NO) and hydrogen sulfide (H2S), proceeds via elusive mechanism(s). Herein
we report the formation of H2S by the action of NO on synthetic [2Fe-2S] clusters
when the reaction environment is capable of providing a formal H(*) (e(-)/H(+)).
Nitrosylation of (NEt4)2[Fe2S2(SPh)4] (1) in the presence of PhSH or (t)Bu3PhOH
results in the formation of (NEt4)[Fe(NO)2(SPh)2] (2) and H2S with the
concomitant generation of PhSSPh or (t)Bu3PhO(*). The amount of H2S generated is
dependent on the electronic environment of the [2Fe-2S] cluster as well as the
type of H(*) donor. Employment of clusters with electron-donating groups or H(*)
donors from thiols leads to a larger amount of H2S evolution. The 1/NO reaction
in the presence of PhSH exhibits biphasic decay kinetics with no deuterium
kinetic isotope effect upon PhSD substitution. However, the rates of decay
increase significantly with the use of 4-MeO-PhSH or 4-Me-PhSH in place of PhSH.
These results provide the first chemical evidence to suggest that [Fe-S] clusters
are likely to be a site for the crosstalk between NO and H2S in biology.
PMID- 25113816
TI - Determinants of glycaemic control in a practice setting: the role of weight loss
and treatment adherence (The DELTA Study).
AB - AIMS: Examine the association between weight loss and adherence with glycaemic
goal attainment in patients with inadequately controlled T2DM. MATERIALS AND
METHODS: Patients >= 18 years with T2DM from a US integrated health system
starting a new class of diabetes medication between 11/1/10 and 4/30/11 (index
date) with baseline HbA1c >= 7.0% were included in this cohort study. Target
HbA1c and weight change were defined at 6-months as HbA1c < 7.0% and >= 3% loss
in body weight. Patient-reported medication adherence was assessed per the
Medication Adherence Reporting Scale. Structural equation modelling was used to
describe simultaneous associations between adherence, weight loss and HbA1c goal
attainment. RESULTS: Inclusion criteria were met by 477 patients; mean (SD) age
59.1 (11.6) years; 50.9% were female; 30.4% were treatment naive; baseline HbA1c
8.6% (1.6); weight 102.0 kg (23.0). Most patients (67.9%) reported being adherent
to the index diabetes medication. At 6 months mean weight change was -1.3 (5.1)
kg (p = 0.39); 28.1% had weight loss of >= 3%. Mean HbA1c change was -1.2% (1.8)
(p< 0.001); 42.8% attained HbA1c goal. Adherent patients (OR 1.70; p = 0.02) and
diabetes therapies that lead to weight loss (metformin, GLP-1) were associated
with weight loss >= 3% (OR 2.96; p< 0.001). Weight loss (OR 3.60; p < 0.001) and
adherence (OR 1.59; p < 0.001) were associated with HbA1c goal attainment.
CONCLUSIONS: Weight loss >= 3% and medication adherence were associated with
HbA1c goal attainment in T2DM; weight loss was a stronger predictor of goal
attainment than medication adherence in this study population. It is important to
consider weight-effect properties, in addition to patient-centric adherence
counselling, when prescribing diabetes therapy.
PMID- 25113817
TI - A feature selection method for classification within functional genomics
experiments based on the proportional overlapping score.
AB - BACKGROUND: Microarray technology, as well as other functional genomics
experiments, allow simultaneous measurements of thousands of genes within each
sample. Both the prediction accuracy and interpretability of a classifier could
be enhanced by performing the classification based only on selected
discriminative genes. We propose a statistical method for selecting genes based
on overlapping analysis of expression data across classes. This method results in
a novel measure, called proportional overlapping score (POS), of a feature's
relevance to a classification task. RESULTS: We apply POS, along-with four widely
used gene selection methods, to several benchmark gene expression datasets. The
experimental results of classification error rates computed using the Random
Forest, k Nearest Neighbor and Support Vector Machine classifiers show that POS
achieves a better performance. CONCLUSIONS: A novel gene selection method, POS,
is proposed. POS analyzes the expressions overlap across classes taking into
account the proportions of overlapping samples. It robustly defines a mask for
each gene that allows it to minimize the effect of expression outliers. The
constructed masks along-with a novel gene score are exploited to produce the
selected subset of genes.
PMID- 25113818
TI - Effects of skin-to-skin contact and breastfeeding at birth on the incidence of
PPH: A physiologically based theory.
AB - BACKGROUND: The importance of optimising maternal/baby psychophysiology has been
integrated into contemporary midwifery theories but not in the detail required to
really understand the underpinning biological basis. METHOD: The functioning of
the autonomic nervous system, as it relates to the uterus is reviewed. The
physiology of myometrial cell contraction and relaxation is outlined. The main
focus is on the factors that affect the availability and uptake of oxytocin and
adrenaline/noradrenaline in the myometrial cells. These are the two key neuro
hormones, active in the 3rd and 4th stages of labour, that affect uterine
contraction and retraction and therefore determine whether the woman will have an
atonic PPH or not. DISCUSSION: The discussion explains and predicts the
physiological functioning of the uterus during the 3rd and 4th stages of labour
when skin-to-skin contact and breastfeeding occurs and when it does not.
CONCLUSION: This biologically based theory hypothesises that to achieve and
maintain eutony and eulochia, midwives and birthing women should ensure early,
prolonged and undisturbed skin-to-skin contact for mother and baby at birth
including easy access for spontaneous breastfeeding.
PMID- 25113819
TI - Targeting perfectionism in anorexia nervosa using a group-based cognitive
behavioural approach: a pilot study.
AB - OBJECTIVE: This study aimed to explore whether a six session cognitive
behavioural group intervention targeting perfectionism is efficacious in reducing
perfectionism in adults with anorexia nervosa in an inpatient setting. METHOD:
Adults with anorexia nervosa received a group perfectionism intervention in an
inpatient setting. Self-report and patient satisfaction questionnaires were
completed at the beginning of the first session and end of the last session.
RESULTS: Significant changes of moderate effect size were observed for overall
perfectionism, concern over mistakes and personal standards dimensions of
perfectionism following participation in the group. These changes were found to
be independent of change in body mass index. CONCLUSIONS: A group cognitive
behavioural approach appears to be efficacious in reducing perfectionism in
adults with anorexia nervosa.
PMID- 25113820
TI - Characteristics impacting on session rating of perceived exertion training load
in Australian footballers.
AB - The relationship between external training load and session rating of perceived
exertion (s-RPE) training load and the impact that playing experience, playing
position and 2-km time-trial performance had on s-RPE training load were
explored. From 39 Australian Football players, 6.9 +/- 4.6 training sessions were
analysed, resulting in 270 samples. Microtechnology devices provided external
training load (distance, average speed, high-speed running distance, player load
(PL) and player loadslow (PLslow)). The external training load measures had
moderate to very large associations (r, 95% CI) with s-RPE training load, average
speed (0.45, 0.35-0.54), high-speed running distance (0.51, 0.42-0.59), PLslow
(0.80, 0.75-0.84), PL (0.86, 0.83-0.89) and distance (0.88, 0.85-0.90).
Differences were described using effect sizes (d +/-95% CL). When controlling for
external training load, the 4- to 5-year players had higher s-RPE training load
than the 0- to 1- (0.44 +/- 0.33) and 2- to 3-year players (0.51 +/- 0.30),
ruckmen had moderately higher s-RPE training load than midfielders (0.82 +/-
0.58), and there was a 0.2% increase in s-RPE training load per 1 s increase in
time-trial (95% CI: 0.07-0.34). Experience, position and time-trial performance
impacted the relationship between external training load and s-RPE training load.
This suggests that a given external training load may result in different
internal responses between athletes, potentially leaving individuals at risk of
overtraining or failing to elicit positive adaptation. It is therefore vital that
coaches and trainers give consideration to these mediators of s-RPE training
load.
PMID- 25113824
TI - Revision of the fish family Kyphosidae (Teleostei: Perciformes).
AB - A molecular phylogenetic analysis with complete species sampling of the family
Kyphosidae revealed several discrepancies with the current taxonomy. We thus
undertook a complete taxonomic revision of all kyphosid genera, i.e. Kyphosus
Lacepede, 1801, and the monotypic Hermosilla Jenkins and Evermann, 1889, Sectator
Jordan and Evermann, 1903 and Neoscorpis Smith, 1931. Species delimitation was
determined on the basis of congruence between (a) monophyletic groupings in the
molecular phylogeny, and (b) clusters of morphological variation in type
material. Twelve species are supported and redescribed. Both Hermosilla and
Sectator are considered junior synonyms of Kyphosus. Kyphosus azureus (Jenkins &
Evermann, 1889) and K. ocyurus (Jordan & Gilbert, 1882) are redescribed
accordingly. We designate a neotype for Kyphosus cornelii (Whitley, 1944), as the
original material is lost, and new material was collected at the type locality
for this study to facilitate comparison with other species of Kyphosus. Kyphosus
sandwicensis (sensu Sauvage, 1880) was found to be a junior synonym of K. elegans
(Peters, 1869). Kyphosus incisor (Cuvier in Cuvier & Valenciennes, 1831) and K.
analogus (Gill, 1862) are considered junior synonyms of K. vaigiensis (Quoy &
Gaimard, 1825). Kyphosus gallveii (Cunningham, 1910), K. pacificus Sakai and
Nakabo, 2004 and K. lutescens (Jordan & Gilbert, 1882) are all considered junior
synonyms of K. sectatrix (Linnaeus, 1758). One of the two syntype specimens of K.
sectatrix was identified as the holotype of Pimelepterus bosquii (Lacepede,
1802), and proved to be a specimen of K. bigibbus Lacepede, 1801. This specimen
is re-assigned as a non-type of K. bigibbus. Full re-descriptions of the
following valid species are presented: K. bigibbus, K. cinerascens (Forsskal,
1775), K. cornelii, K. elegans, K. hawaiiensis Sakai and Nakabo, 2004, K. gladius
Knudsen and Clements, 2013, K. sydneyanus (Gunther, 1886) and K. vaigiensis,
together with a key to the family. The distribution of Kyphosus species is
reconsidered based on our taxonomic revision, indicating that four species (K.
bigibbus, K. cinerascens, K. sectatrix and K. vaigiensis) occur in both the
Atlantic and Indo-Pacific regions.
PMID- 25113821
TI - Impact of single-cell genomics and metagenomics on the emerging view of
extremophile "microbial dark matter".
AB - Despite >130 years of microbial cultivation studies, many microorganisms remain
resistant to traditional cultivation approaches, including numerous candidate
phyla of bacteria and archaea. Unraveling the mysteries of these candidate phyla
is a grand challenge in microbiology and is especially important in habitats
where they are abundant, including some extreme environments and low-energy
ecosystems. Over the past decade, parallel advances in DNA amplification, DNA
sequencing and computing have enabled rapid progress on this problem,
particularly through metagenomics and single-cell genomics. Although each
approach suffers limitations, metagenomics and single-cell genomics are
particularly powerful when combined synergistically. Studies focused on extreme
environments have revealed the first substantial genomic information for several
candidate phyla, encompassing putative acidophiles (Parvarchaeota), halophiles
(Nanohaloarchaeota), thermophiles (Acetothermia, Aigarchaeota, Atribacteria,
Calescamantes, Korarchaeota, and Fervidibacteria), and piezophiles
(Gracilibacteria). These data have enabled insights into the biology of these
organisms, including catabolic and anabolic potential, molecular adaptations to
life in extreme environments, unique genomic features such as stop codon
reassignments, and predictions about cell ultrastructure. In addition, the rapid
expansion of genomic coverage enabled by these studies continues to yield
insights into the early diversification of microbial lineages and the
relationships within and between the phyla of Bacteria and Archaea. In the next 5
years, the genomic foliage within the tree of life will continue to grow and the
study of yet-uncultivated candidate phyla will firmly transition into the post
genomic era.
PMID- 25113823
TI - Natural anionic polymer acts as highly efficient trypsin inhibitor based on an
electrostatic interaction mechanism.
AB - Sodium alginate (SA), acting as a trypsin inhibitor by means of electrostatic
interaction, is studied. The half-maximal inhibitory concentration (IC50 = 0.05
MUg mL(-1) ) of this natural anionic polymer is about 400 times lower than that
of commercial soybean trypsin inhibitor (STI). Unlike the Ca(2+) -deprivation
mechanisms, its inhibition may be attributed to preventing the trypsin active
site (TAS) from accessing the macromolecular substrates instead of denaturing it.
SA is an efficient, innocuous, and cost-effective inhibitory excipient that can
be conveniently used in many peptide and protein dosage formulations.
PMID- 25113822
TI - Dark matter in archaeal genomes: a rich source of novel mobile elements, defense
systems and secretory complexes.
AB - Microbial genomes encompass a sizable fraction of poorly characterized, narrowly
spread fast-evolving genes. Using sensitive methods for sequences comparison and
protein structure prediction, we performed a detailed comparative analysis of
clusters of such genes, which we denote "dark matter islands", in archaeal
genomes. The dark matter islands comprise up to 20% of archaeal genomes and show
remarkable heterogeneity and diversity. Nevertheless, three classes of entities
are common in these genomic loci: (a) integrated viral genomes and other mobile
elements; (b) defense systems, and (c) secretory and other membrane-associated
systems. The dark matter islands in the genome of thermophiles and mesophiles
show similar general trends of gene content, but thermophiles are substantially
enriched in predicted membrane proteins whereas mesophiles have a greater
proportion of recognizable mobile elements. Based on this analysis, we predict
the existence of several novel groups of viruses and mobile elements, previously
unnoticed variants of CRISPR-Cas immune systems, and new secretory systems that
might be involved in stress response, intermicrobial conflicts and biogenesis of
novel, uncharacterized membrane structures.
PMID- 25113825
TI - Topological defects in cholesteric liquid crystals induced by monolayer domains
with orientational chirality.
AB - Unless stabilized by colloids or confinement with well-defined boundary
conditions, defects in liquid crystals remain elusive short-lived objects that
tend to disappear with time to minimize the medium's free energy. In this work we
use multimodal three-dimensional imaging to visualize cholesteric director
structures to show that self-assembled chiral molecular monolayer domains can
stabilize topologically constrained defect configurations when in contact with a
cholesteric liquid crystal. The cholesteric liquid crystal, having features of
both coarse-grained lamellar and nematic liquid crystal with chiral symmetry
breaking, allows us to explore the interplay of chirality and implications of
layering on the formed defects and director configurations.
PMID- 25113826
TI - Desulfurization of thianthrene by a Gordonia sp. IITR100.
AB - Thianthrene (TA) was desulfurized by an isolated strain, Gordonia sp. IITR100.
The reaction is accompanied with the formation of TA-sulfoxide, TA-sulfone and 2
phenylsulfanylphenol. The formed 2-phenylsulfanylphenol undergoes further
oxidation to o-hydroxyphenyl phenylsulfone that accumulates as an end product.
Metabolism of TA to TA-sulfone can also occur by E. coli-DszC i.e. E. coli cells
that were harboring the gene coding for the enzyme dibenzothiophene desulfurase
C. When presented to E. coli-DszC in a binary combination with dibenzothiophene,
TA metabolism was completely inhibited. Metabolism of TA-TA-sulfone by E. coli
DszC, as well as the nature of metabolites formed by IITR100, suggests that the
desulfurization pathway for TA is similar to that of the thiophenic compounds.
This is first report on the desulfurization of thianthrene, and has implications
on biodesulfurization when multiple sulfur compounds are present together.
PMID- 25113827
TI - [Organ and function preservation in urethral cancer].
AB - Primary urethral carcinomas are rare tumors that can occur both in men and women.
Histological patterns of these tumors are mixed, urothelial tumors occur as well
as squamous cell tumors or adenocarcinomas.There are different clinical factors
that define clinical prognosis, and the 1- and 5-year cancer-free survival is 75%
and 54%. Therapy of locally limited disease is surgical resection, and organ
preserving treatment is possible if negative frozen sections prove complete
surgical resection. However, in men a perineal urethrostomy might be necessary,
and in women there is a high risk of urinary incontinence if more than 2 cm of
the distal urethra is resected.In case of locally advanced tumors or tumors of
the proximal urethra, a radical urethrectomy with supravesical urinrary diversion
is necessary. In some cases neoadjuvant (radio-)chemotherapy may be an option.
PMID- 25113828
TI - Facile, one-pot solvothermal method to synthesize ultrathin Sb2S3 nanosheets
anchored on graphene.
AB - Ultrathin, two-dimensional (2D) nanosheets of layered transition-metal
chalcogenides are theoretically and technologically intriguing. However, it still
remains a great challenge to synthesize ultrathin nanosheets because of the lack
of an intrinsic driving force for the anisotropic growth of 2D superposed
microstructures. Here we demonstrate, for the first time to our knowledge, the in
situ synthesis of large-scale ultrathin Sb2S3 nanosheets on graphene sheets (G)
by solvothermal method in a water-ethylene glycol mixed solvent. Owing to the
synergetic chemical coupling effects between G and Sb2S3, Sb2S3-G hybrid
nanosheets exhibit high catalytic performance for the degradation of methylene
blue in the presence of H2O2. Moreover, it was found that the resulting Sb2S3-G
shows good electrocatalytic activity towards hydrazine oxidation. This work not
only offers a low-cost and high performance alternative technology for
synthesizing sheet-like Sb2S3, but also opens the door toward the fabrication of
varying types of metal sulfide-graphene nanomaterials that will have wide
applications in catalysis, environmental, and new energy fields.
PMID- 25113830
TI - External NAD(P)H dehydrogenases in Acanthamoeba castellanii mitochondria.
AB - The mitochondrial respiratory chain of plants and some fungi contains multiple
rotenone-insensitive NAD(P)H dehydrogenases, of which at least two are located on
the outer surface of the inner membrane (i.e., external NADH and external NADPH
dehydrogenases). Annotated sequences of the putative alternative NAD(P)H
dehydrogenases of the protozoan Acanthamoeba castellanii demonstrated similarity
to plant and fungal sequences. We also studied activity of these dehydrogenases
in isolated A. castellanii mitochondria. External NADPH oxidation was observed
for the first time in protist mitochondria. The coupling parameters were similar
for external NADH oxidation and external NADPH oxidation, indicating similar
efficiencies of ATP synthesis. Both external NADH oxidation and external NADPH
oxidation had an optimal pH of 6.8 independent of relevant ubiquinol-oxidizing
pathways, the cytochrome pathway or a GMP-stimulated alternative oxidase. The
maximal oxidizing activity with external NADH was almost double that with
external NADPH. However, a lower Michaelis constant (K(M)) value for external
NADPH oxidation was observed compared to that for external NADH oxidation.
Stimulation by Ca(2+) was approximately 10 times higher for external NADPH
oxidation, while NADH dehydrogenase(s) appeared to be slightly dependent on
Ca(2+). Our results indicate that external NAD(P)H dehydrogenases similar to
those in plant and fungal mitochondria function in mitochondria of A.
castellanii.
PMID- 25113829
TI - The social amoeba Polysphondylium pallidum loses encystation and sporulation, but
can still erect fruiting bodies in the absence of cellulose.
AB - Amoebas and other freely moving protists differentiate into walled cysts when
exposed to stress. As cysts, amoeba pathogens are resistant to biocides,
preventing treatment and eradication. Lack of gene modification procedures has
left the mechanisms of encystation largely unexplored. Genetically tractable
Dictyostelium discoideum amoebas require cellulose synthase for formation of
multicellular fructifications with cellulose-rich stalk and spore cells. Amoebas
of its distant relative Polysphondylium pallidum (Ppal), can additionally encyst
individually in response to stress. Ppal has two cellulose synthase genes, DcsA
and DcsB, which we deleted individually and in combination. Dcsa- mutants formed
fruiting bodies with normal stalks, but their spore and cyst walls lacked
cellulose, which obliterated stress-resistance of spores and rendered cysts
entirely non-viable. A dcsa-/dcsb- mutant made no walled spores, stalk cells or
cysts, although simple fruiting structures were formed with a droplet of amoeboid
cells resting on an sheathed column of decaying cells. DcsB is expressed in
prestalk and stalk cells, while DcsA is additionally expressed in spores and
cysts. We conclude that cellulose is essential for encystation and that cellulose
synthase may be a suitable target for drugs to prevent encystation and render
amoeba pathogens susceptible to conventional antibiotics.
PMID- 25113831
TI - Molecular revision of the genus Wallaceina.
AB - This work is focused on the molecular revision of the genus Wallaceina
established in the very twilight of the classical morphotype-based approach to
classification of the Trypanosomatidae. The genus was erected due to the presence
of a unique variant of endomastigotes. In molecular phylogenetic studies four
described species of Wallaceina were shown to be extremely close to each other
and to some other undescribed isolates clustered within Leishmaniinae clade,
while three recently included species formed a separate clade. Our results of
morphological and molecular phylogenetic analyses demonstrated that all
Leishmaniinae-bound wallaceinas are just different isolates of the same species
that we rename back to Crithidia brevicula Frolov, Malysheva, 1989. To
accommodate former Wallaceina spp. phylogenetically distant from the genus
Crithidia, we propose a new generic name Wallacemonas Kostygov et Yurchenko,
2014.
PMID- 25113832
TI - Associations between body mass and papillary thyroid cancer stage and tumor size:
a population-based study.
AB - PURPOSE: The incidence of large thyroid tumors has increased over the past
decades, suggesting that improved diagnosis is not the only driver of increased
thyroid cancer incidence. Obesity has recently been implicated as an independent
risk factor for thyroid cancer in specific populations. We aimed to investigate
whether thyroid tumor size and advanced stage of diagnosis is associated with the
obesity epidemic, for the first time, in a US population-based cohort. METHODS:
We leveraged existing data and linked 1,077 papillary thyroid cancer patients
from the Nevada Central Cancer Registry to the Department of Motor Vehicle
dataset. Tumor size and cancer stage were assessed from cancer registry records,
and obesity was obtained using height and weight in the Department of Motor
Vehicle records and measured by a body mass index greater than 25 kg/m(2).
RESULTS: Crude analysis showed obesity as was associated with tumors larger than
2 cm [odds ratio (OR) 1.50, p = 0.0423] and advanced cancer stage (stage III and
IV) (OR 1.40, p = 0.0111). After adjusting for confounders, a significant
association was still observed between obesity and tumor larger than 2 cm (OR
1.53, p = 0.0339). A marginally significant association was shown between obesity
and advanced cancer stage (OR 1.29, p = 0.0649). CONCLUSION: As thyroid cancer
incidence continues to increase, this study's finding that obesity was
significantly associated with larger tumor size and marginally significantly
associated with advanced tumor stage can help establish new preventative actions
and identify new target populations for interventions.
PMID- 25113833
TI - Effect of different sulfides on cadmium distribution during sludge combustion
based on experimental and thermodynamic calculation approaches.
AB - The effects of sulfur compounds on the migration of a semi-volatile heavy metal
(cadmium) during sludge incineration were investigated with two methods, i.e.,
experiments in a tubular furnace reactor and thermodynamic equilibrium
calculations. The representative typical sludge with and without the addition of
sulfur compounds was incinerated at 850 degrees C. The partitioning of Cd among
the solid phase (bottom ash) and gas phase (fly ash and flue gas) was quantified.
The results indicate that sulfur compounds in the elemental form and a reduced
state could stabilize Cd in the form of CdS, aluminosilicate minerals, and
polymetallic sulfides, whereas sulfur in the oxidized forms slightly increases Cd
volatilization during incineration. For Cd solidification points, the inhibition
effect on the volatilization of Cd is as follows: S > Na2SO4 > Na2S. Chemical
equilibrium calculations indicate that sulfur binds with Cd and alters Cd
speciation at low temperatures (<950 K). Furthermore, SiO2- and Al2O3-containing
minerals can function as sorbents stabilizing Cd as condensed phase solids
(CdSiO4 and CdAl2O4) according to the results of equilibrium calculations. These
findings provide useful information for understanding the partitioning of Cd and
thus facilitate the development of strategies to control Cd volatilization during
sludge incineration.
PMID- 25113834
TI - In vivo toxicity of orally administrated silicon dioxide nanoparticles in healthy
adult mice.
AB - The increasing use of silica nanoparticles (SiNPs) in various applications
including industrial, agriculture, and medicine has raised concerns about their
potential risks to human health. Various nanotoxicity researches have been done
on the assessment of SiNPs' toxic effects; however, a few in vivo investigations
exist. In this investigation, an in vivo study was done in order to evaluate the
oral toxicity of SiNPs. The biochemical levels of 19 different serum parameters
were assessed. Moreover, the histopathological changes have been examined as
well. We showed that SiNPs with diameters of 10-15 nm in size can cause
significant changes in albumin, cholesterol, triglyceride, total protein, urea,
HDL, and LDL as well as in alkaline phosphatase and aspartate aminotransferase
activity. In addition, histopathological examinations demonstrated that SiNPs
have toxic effects on various tissues including liver, kidney, lung, and testis.
PMID- 25113835
TI - PEGylated carboxyhemoglobin bovine (SANGUINATE): results of a phase I clinical
trial.
AB - PEGylated carboxyhemoglobin bovine (SANGUINATE) is a dual action carbon monoxide
releasing (CO)/oxygen (O2 ) transfer agent for the treatment of hypoxia. Its
components inhibit vasoconstriction, decrease extravasation, limit reactive
oxygen species production, enhance blood rheology, and deliver oxygen to the
tissues. Animal models of cerebral ischemia, peripheral ischemia, and myocardial
ischemia demonstrated SANGUINATE's efficacy in reducing myocardial infarct size,
limiting necrosis from cerebral ischemia, and promoting more rapid recovery from
hind limb ischemia. In a Phase I trial, three cohorts of eight healthy volunteers
received single ascending doses of 80, 120, or 160 mg/kg of SANGUINATE. Two
volunteers within each cohort served as a saline control. There were no serious
adverse events. Serum haptoglobin decreased, but did not appear to be dose
related. The T1/2 was dose dependent and ranged from 7.9 to 13.8 h. In addition
to the Phase I trial, SANGUINATE was used under an expanded access emergency
Investigational New Drug. SANGUINATE was found to be safe and well tolerated in a
Phase I clinical trial, and therefore it will advance into further clinical
trials in patients.
PMID- 25113836
TI - Mitochondrial dynamics controlled by mitofusins define organelle positioning and
movement during mouse oocyte maturation.
AB - Mitochondria are abundant in fully grown mammalian oocytes with a unique
spherical morphology, but the mechanisms controlling mitochondria behavior are
not well understood. Here we describe for the first time the control of
mitochondrial behavior in mouse oocytes by a fusion/fission mechanism. Mitofusins
(Mfn1 and Mfn2) and OPA1 proteins are required for outer and inner mitochondrial
membrane fusion, respectively, whereas Drp1 is the key regulator of mitochondrial
fission. We show that mouse oocytes express the Mfn1, Mfn2, Opa1 and Drp1
proteins, both in immature and mature oocytes at similar levels. Overexpression
of Mfn1 or Mfn2 causes marked mitochondrial aggregation, particularly in the
perinuclear region during meiotic progression. Tracking of mitochondria with
chromosomes or endoplasmic reticulum (ER) throughout oocyte maturation
demonstrates that Mfn1 and Mfn2-promoted mitochondrial aggregation disturbs the
spatiotemporal dynamic of the chromosomes and ER, respectively. Our findings
suggest that organelle dynamics are co-ordinately controlled during meiotic
division, and an imbalance of mitochondrial fusion/fission leads to
disorganization of the organelle compartments.
PMID- 25113837
TI - Fluid overload in a South African pediatric intensive care unit.
AB - OBJECTIVE: Fluid resuscitation is integral to resuscitation guidelines and
critical care. However, fluid overload (FO) yields increased morbidity. METHODS:
Prospective observational study of Red Cross War Memorial Children's Hospital
pediatric intensive care unit admissions (February to March 2013). FO % = (fluid
in minus fluid out) [liters]/weight [kg] * 100%. PRIMARY OUTCOMES: FO >= 10%, 28
day mortality. RESULTS: Median [interquartile range (IQR)] age: 9.5 (2.0-39.0)
months, median (IQR) admission weight: 7.9 (3.6-13.7) kg. Median (IQR) FO with
admission weight: 3.5 (2.1-4.9)%; three patients had FO >= 10%. The 28 day
mortality was 10% (n = 10). Patients who died had higher mean (IQR) FO using
admission weight [4.9 (2.9-9.3)% vs. 3.4 (1.9-4.8)%; p = 0.04]. CONCLUSIONS: Low
FO >= 10% prevalence with 28 day mortality 10%. Higher FO% with admission weight
associated with mortality (p = 0.04). We advocate further investigation of FO% as
a simple bedside tool.
PMID- 25113838
TI - Drug therapy: keeping rats in the dark sheds light on tamoxifen resistance.
PMID- 25113841
TI - Genetics: new molecular classification of gastric adenocarcinoma proposed by The
Cancer Genome Atlas.
PMID- 25113839
TI - Cancer-related fatigue--mechanisms, risk factors, and treatments.
AB - Fatigue is one of the most common adverse effects of cancer that might persist
for years after treatment completion in otherwise healthy survivors. Cancer
related fatigue causes disruption in all aspects of quality of life and might be
a risk factor of reduced survival. The prevalence and course of fatigue in
patients with cancer have been well characterized and there is growing
understanding of the underlying biological mechanisms. Inflammation seems to have
a key role in fatigue before, during, and after cancer-treatment. However, there
is a considerable variability in the presentation of cancer-related fatigue, much
of which is not explained by disease-related or treatment-related
characteristics, suggesting that host factors might be important in the
development and persistence of this symptom. Indeed, longitudinal studies have
identified genetic, biological, psychosocial, and behavioural risk factors
associated with cancer-related fatigue. Although no current gold-standard
treatment for fatigue is available, a variety of intervention approaches have
shown beneficial effects in randomized controlled trials, including physical
activity, psychosocial, mind-body, and pharmacological treatments. This Review
describes the mechanisms, risk factors, and possible interventions for cancer
related fatigue, focusing on recent longitudinal studies and randomized trials
that have targeted fatigued patients.
PMID- 25113843
TI - l-carnitine supplementation during vitrification of mouse germinal vesicle stage
oocytes and their subsequent in vitro maturation improves meiotic spindle
configuration and mitochondrial distribution in metaphase II oocytes.
AB - STUDY QUESTION: How does l-carnitine (LC) supplementation during vitrification
and in vitro maturation (IVM) of germinal vesicle stage (GV)-oocytes improve the
developmental competence of the resultant metaphase II (MII) oocytes? SUMMARY
ANSWER: LC supplementation during both vitrification of GV-oocytes and their
subsequent IVM improved nuclear maturation as well as meiotic spindle assembly
and mitochondrial distribution in MII oocytes. WHAT IS KNOWN ALREADY:
Vitrification of GV-oocytes results in a lower success rate of blastocyst
development compared with non-vitrified oocytes. LC supplementation during both
vitrification and IVM of mouse GV-oocytes significantly improves embryonic
development after IVF. STUDY DESIGN, SIZE, DURATION: GV-oocytes were collected
from (B6.DBA)F1 and B6 mouse strains and subjected to vitrification and warming
with or without 3.72 mM LC supplementation. After IVM with or without LC
supplementation, the rate of nuclear maturation and the quality of MII oocytes
were evaluated. At least 20 oocytes/group were examined, and each experiment was
repeated at least three times. All experiments were conducted during 2013-2014.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Extrusion of the first polar body in
IVM oocytes was observed as an indication of nuclear maturation. Spindle assembly
and chromosomal alignment were examined by immunostaining of alpha-tubulin and
nuclear staining with 4,6-diamidino-2-phenylindole (DAPI). Mitochondrial
distribution and oxidative activity were measured by staining with Mitotracker
Green Fluorescence Mitochondria (Mitotracker Green FM) and
chloromethyltetramethylrosamine (Mitotracker Orange CMTMRos), respectively. ATP
levels were determined by using the Bioluminescent Somatic Cell Assay Kit. MAIN
RESULTS AND THE ROLE OF CHANCE: LC supplementation during both vitrification and
IVM of GV-oocytes significantly increased the proportions of oocytes with normal
MII spindles to the levels comparable with those of non-vitrified oocytes in both
mouse strains. While vitrification of GV-oocytes lowered the proportions of MII
oocytes with peripherally concentrated mitochondrial distribution compared with
non-vitrified oocytes, LC supplementation significantly increased the proportion
of such oocytes in the (B6.DBA)F1 strain. LC supplementation decreased the
proportion of oocytes with mitochondrial aggregates in both vitrified and non
vitrified oocytes in the B6 strain. The oxidative activity of mitochondria was
mildly decreased by vitrification and drastically increased by LC supplementation
irrespective of vitrification in both mouse strains. No change was found in ATP
levels irrespective of vitrification or LC supplementation. Results were
considered to be statistically significant at P < 0.05 by either chi(2)- or t
test. LIMITATIONS, REASONS FOR CAUTION: It remains to be tested whether
beneficial effect of LC supplementation during vitrification and IVM of GV
oocytes leads to fetal development and birth of healthy offspring after embryo
transfer to surrogate females. WIDER IMPLICATIONS OF THE FINDINGS: This protocol
has the potential to improve the quality of vitrified human oocytes and embryos
during assisted reproduction treatment. STUDY FUNDING/COMPETING INTEREST:
Partially supported by the Natural Sciences and Engineering Research Council of
Canada (NSERC) Discovery Grant and Mitacs Elevate Postdoctoral Fellowship,
Canada.
PMID- 25113842
TI - Quantitative multimodality imaging in cancer research and therapy.
AB - Advances in hardware and software have enabled the realization of clinically
feasible, quantitative multimodality imaging of tissue pathophysiology. Earlier
efforts relating to multimodality imaging of cancer have focused on the
integration of anatomical and functional characteristics, such as PET-CT and
single-photon emission CT (SPECT-CT), whereas more-recent advances and
applications have involved the integration of multiple quantitative, functional
measurements (for example, multiple PET tracers, varied MRI contrast mechanisms,
and PET-MRI), thereby providing a more-comprehensive characterization of the
tumour phenotype. The enormous amount of complementary quantitative data
generated by such studies is beginning to offer unique insights into
opportunities to optimize care for individual patients. Although important
technical optimization and improved biological interpretation of multimodality
imaging findings are needed, this approach can already be applied informatively
in clinical trials of cancer therapeutics using existing tools. These concepts
are discussed herein.
PMID- 25113845
TI - Quality testing of human albumin by capillary electrophoresis using thermally
cross-linked poly(vinyl pyrrolidone)-coated fused-silica capillary.
AB - To detect the quality of medicinal human albumin by capillary electrophoresis, we
produced a fused-silica capillary coated with thermally cross-linked poly(vinyl
pyrrolidone) to prohibit protein adsorption. This type of capillary was easily
obtained by injecting an aqueous poly(vinyl pyrrolidone) solution into a fused
silica capillary and thermally annealing it at 200 degrees C. Notably, stable and
low electro-osmotic flow was obtained in the poly(vinyl pyrrolidone)-coated
capillary at pH 2.20-9.00, and the separation of a mixture of four basic proteins
indicated that the poly(vinyl pyrrolidone)-coated capillary exhibits excellent
repeatability and separation efficiency; moreover, the separation of these four
basic proteins could even be achieved at pH 7.00. The protein recovery percentage
of human serum albumin in a single-protein solution and a mixed blood proteins
solution was determined to be 97.03 and 95.40% in the poly(vinyl pyrrolidone)50-3
(representing the concentration of the capillary-injected poly(vinyl pyrrolidone)
aqueous solution, 50 mg/mL, and thermal annealing time, 3 h) capillary,
respectively. Based on these results, we used the poly(vinyl pyrrolidone)50-3
coated capillary to quantify the protein content of human albumin, and the
results obtained from run to run, day to day and capillary to capillary
demonstrated that the coated capillary could be used for quality testing
commercially available human albumin.
PMID- 25113840
TI - Vessel caliber--a potential MRI biomarker of tumour response in clinical trials.
AB - Our understanding of the importance of blood vessels and angiogenesis in cancer
has increased considerably over the past decades, and the assessment of tumour
vessel calibre and structure has become increasingly important for in vivo
monitoring of therapeutic response. The preferred method for in vivo imaging of
most solid cancers is MRI, and the concept of vessel-calibre MRI has evolved
since its initial inception in the early 1990s. Almost a quarter of a century
later, unlike traditional contrast-enhanced MRI techniques, vessel-calibre MRI
remains widely inaccessible to the general clinical community. The narrow
availability of the technique is, in part, attributable to limited awareness and
a lack of imaging standardization. Thus, the role of vessel-calibre MRI in early
phase clinical trials remains to be determined. By contrast, regulatory approvals
of antiangiogenic agents that are not directly cytotoxic have created an urgent
need for clinical trials incorporating advanced imaging analyses, going beyond
traditional assessments of tumour volume. To this end, we review the field of
vessel-calibre MRI and summarize the emerging evidence supporting the use of this
technique to monitor response to anticancer therapy. We also discuss the
potential use of this biomarker assessment in clinical imaging trials and
highlight relevant avenues for future research.
PMID- 25113846
TI - Three dimensional analysis of the composition in solid alloys by variable probe
in scanning transmission electron microscopy.
AB - This paper reports on a novel approach to quantitatively reconstruct the column
by column composition and the 3D distribution of guest atoms inside a host matrix
by scanning transmission electron microscopy high angle annular dark field
technique. We propose a new mathematical framework that allows to jointly analyze
the information from a set of experiments with variable beam convergence and/or
defocus. Our scheme allows to reconstruct the atomic distribution along the
imaged columns from the measured intensity, for any dependence of the probe
intensity on the depth. It is therefore well suited to incorporate channeling
effects that are usually neglected in other approaches. As a case study, we focus
here on the systematic variation of the beam convergence that permits to set the
maximum of the channeling oscillations at different depths. We aim here to define
the reliability and the limitation of this technique by the application of the
method to accurate dynamic simulations in the case of the InGaN alloy.
PMID- 25113844
TI - Transcriptome profiling of CTLs regulated by rapamycin using RNA-Seq.
AB - Memory programming of cytotoxic T cells (CTLs) by inflammatory cytokines can be
regulated by mammalian target of rapamycin (mTOR). We have shown that inhibition
of mTOR during CTL activation leads to the enhancement of memory, but the
molecular mechanisms remain largely unknown. Using high-throughput RNA-Seq, we
identified genes and functions in mouse CTLs affected by mTOR inhibition through
rapamycin. Of the 43,221 identified transcripts, 184 transcripts were
differentially expressed after rapamycin treatment, corresponding to 128
annotated genes. Of these genes, 114 were downregulated and only 14 were
upregulated. Most importantly, 50 of them are directly related to cell death and
survival. In addition, several genes such as CD62L are related to migration.
Furthermore, we predicted downregulation of transcriptional regulators based on
the total differentially expressed genes, as well as the subset of apoptosis
related genes. Quantitative PCR confirmed the differential expressions detected
in RNA-Seq. We conclude that the regulatory function of rapamycin may work
through inhibition of multiple genes related to apoptosis and migration, which
enhance CTL survival into memory.
PMID- 25113847
TI - Theoretical modeling of low-energy electronic absorption bands in reduced
cobaloximes.
AB - The reduced Co(I) states of cobaloximes are powerful nucleophiles that play an
important role in the hydrogen-evolving catalytic activity of these species. In
this work we analyze the low-energy electronic absorption bands of two cobaloxime
systems experimentally and use a variety of density functional theory and
molecular orbital ab initio quantum chemical approaches. Overall we find a
reasonable qualitative understanding of the electronic excitation spectra of
these compounds but show that obtaining quantitative results remains a
challenging task.
PMID- 25113849
TI - The role of the cytopathologist's interpretation in achieving diagnostic adequacy
of head and neck fine needle aspirates.
AB - OBJECTIVE: We aimed to assess the potential role of interpretation by
cytopathologists on the level of diagnostic adequacy of head and neck fine needle
aspirations (FNAs). METHODS: An audit ('first audit') was performed between 1 May
2007 and 30 April 2008 using data from three different hospitals (A, B and C).
The specimens were interpreted by two cytopathologists with specific experience
in head and neck pathology in hospitals A and B, and by any of the eight
cytopathologists (only two of whom were experienced in head and neck
cytopathology) in hospital C. Following the analysis of the initial findings,
there was a change in practice in hospital C, after which specimens were also
read only by two experienced cytopathologists. A new audit ('second audit') was
then performed between 20 January 2011 and 20 December 2012 in the same three
hospitals. RESULTS: During the first audit, the diagnostic adequacy of FNAs from
hospital C was 84.2% compared with 96.6% in hospital A and 97.7% in hospital B (P
= 0.000). No significant difference in the diagnostic adequacy rate of the FNAs
performed in hospitals A and B was found when comparing the first and second
audits. The FNA diagnostic adequacy for hospital C increased significantly in the
second relative to the first audit (95.5% versus 84.2%, P = 0.000). CONCLUSIONS:
Our study confirms that expert cytology interpretation is important in achieving
optimal diagnostic adequacy of head and neck FNAs.
PMID- 25113848
TI - Identification of germinal centres in the lymph node of a patient with
hyperimmunoglobulin M syndrome associated with congenital rubella.
AB - BACKGROUND: The hyper immunoglobulin M syndrome (HIM) associated with congenital
rubella infection (rHIM) is an extremely rare disorder, where patients have
elevated serum IgM in association with reduced IgG and IgA. We have previously
shown that in contrast to X-linked HIM (XHIM), a patient with well-characterised
rHIM is able to express functional CD40 ligand, undergo immunoglobulin isotype
switching and to generate memory B cells. Here we describe the ultrastructural
features of an excised lymph node from this patient. METHODS: An inguinal lymph
node was surgically removed and examined histologically as well as by
immunohistochemistry. It was then stained with multiple fluorescent dyes to
visualize the cellular interactions within the node. Flow cytometry was
undertaken on a cellular suspension from the node. FINDINGS: Our patient has
normal lymph node architecture by light microscopy. Immunohistochemistry studies
showed the presence of scattered germinal centres. Polychromatic
immunofluorescence staining showed disruption of the architecture with mostly
abnormal germinal centres. A small number of relatively intact germinal centres
were identified. Both IgM and IgG bearing cells were identified in germinal
centres. INTERPRETATION: In contrast to XHIM where germinal centres are absent,
the presence of small numbers of relatively normal germinal centres explain our
previous identification of isotype switched memory B cells in rHIM.
PMID- 25113850
TI - Diurnal and nocturnal activity budgets of zoo elephants in an outdoor facility.
AB - The present study examined the activity budgets of 15 African elephants (1 bull,
6 cows, 2 male juveniles, 2 female juveniles, and 4 male calves) living at the
San Diego Zoo Safari Park during the summers of 2010 and 2011. Onsite behavioral
data (n = 600 hr) were collected for approximately 12 weeks from 0400 to 0830 and
1100 to 2400 during the 2010 and 2011 summer season. Foraging was the most common
behavior state during the day followed by resting, and walking. During the
evening hours, the elephants spent majority of their time foraging, resting, and
sleeping. The average rate of self-maintenance behavior events (dust, wallow,
etc.) increased from 0600 to 0700, 1100 to 1500, and from 1700 to 1900. Positive
social behavior events (touch other, play, etc.) remained high from 0500 to 2300,
with peaks at 0600, 1300, 1500, and 1900. Negative social events occurred at low
rates throughout the day and night, with peaks at 0600, 1900, and 2200. The
majority of positive behavior events during the daylight and nighttime hours
involved the mother-calf pairs. Furthermore, the calves and juveniles initiated
approximately 60% of all social events during the daytime and 57% of all social
interactions at night. The results of this study demonstrate the differences
between diurnal and nocturnal activity budgets of a multi-age and sex elephant
herd in a zoological facility, which highlights the importance of managing
elephants to meet their 24 hr behavioral needs.
PMID- 25113851
TI - Diagnostic value of the 4Ts score for heparin-induced thrombocytopenia in the
critically ill.
PMID- 25113852
TI - Finding faces among faces: human faces are located more quickly and accurately
than other primate and mammal faces.
AB - We tested the specificity of human face search efficiency by examining whether
there is a broad window of detection for various face-like stimuli-human and
animal faces-or whether own-species faces receive greater attentional allocation.
We assessed the strength of the own-species face detection bias by testing
whether human faces are located more efficiently than other animal faces, when
presented among various other species' faces, in heterogeneous 16-, 36-, and 64
item arrays. Across all array sizes, we found that, controlling for distractor
type, human faces were located faster and more accurately than primate and mammal
faces, and that, controlling for target type, searches were faster when
distractors were human faces compared to animal faces, revealing more efficient
processing of human faces regardless of their role as targets or distractors
(Experiment 1). Critically, these effects remained when searches were for
specific species' faces (human, chimpanzee, otter), ruling out a category-level
explanation (Experiment 2). Together, these results suggest that human faces may
be processed more efficiently than animal faces, both when task-relevant
(targets) and task-irrelevant (distractors), even in direct competition with
other faces. These results suggest that there is not a broad window of detection
for all face-like patterns but that human adults process own-species' faces more
efficiently than other species' faces. Such own-species search efficiencies may
arise through experience with own-species faces throughout development or may be
privileged early in development, due to the evolutionary importance of
conspecifics' faces.
PMID- 25113854
TI - Association between non-medical prescription drug use and personality traits
among young Swiss men.
AB - AIM: To investigate the relationships between six classes of non-medical
prescription drug use (NMPDU) and five personality traits. METHODS:
Representative baseline data on 5777 Swiss men around 20 years old were taken
from the Cohort Study on Substance Use Risk Factors. NMPDU of opioid analgesics,
sedatives/sleeping pills, anxiolytics, antidepressants, beta-blockers and
stimulants over the previous 12 months was measured. Personality was assessed
using the Brief Sensation Seeking Scale; attention deficit-hyperactivity (ADH)
using the Adult Attention-Deficit-Hyperactivity Disorder Self-Report Scale; and
aggression/hostility, anxiety/neuroticism and sociability using the Zuckerman
Kuhlmann Personality Questionnaire. Logistic regression models for each
personality trait were fitted, as were seven multiple logistic regression models
predicting each NMPDU adjusting for all personality traits and covariates.
RESULTS: Around 10.7% of participants reported NMPDU in the last 12 months, with
opioid analgesics most prevalent (6.7%), then sedatives/sleeping pills (3.0%),
anxiolytics (2.7%), and stimulants (1.9%). Sensation seeking (SS), ADH,
aggression/hostility, and anxiety/neuroticism (but not sociability) were
significantly positively associated with at least one drug class (OR varied
between 1.24, 95%CI: 1.04-1.48 and 1.86, 95%CI: 1.47-2.35). Aggression/hostility,
anxiety/neuroticism and ADH were significantly and positively related to almost
all NMPDU. Sociability was inversely related to NMPDU of sedatives/sleeping pills
and anxiolytics (OR, 0.70; 95%CI: 0.51-0.96 and OR, 0.64; 95%CI: 0.46-0.90,
respectively). SS was related only to stimulant use (OR, 1.74; 95%CI: 1.14-2.65).
CONCLUSION: People with higher scores for ADH, aggression/hostility and
anxiety/neuroticism are at higher risk of NMPDU. Sociability appeared to protect
from NMPDU of sedatives/sleeping pills and anxiolytics.
PMID- 25113853
TI - Task specificity of attention training: the case of probability cuing.
AB - Statistical regularities in our environment enhance perception and modulate the
allocation of spatial attention. Surprisingly little is known about how learning
induced changes in spatial attention transfer across tasks. In this study, we
investigated whether a spatial attentional bias learned in one task transfers to
another. Most of the experiments began with a training phase in which a search
target was more likely to be located in one quadrant of the screen than in the
other quadrants. An attentional bias toward the high-probability quadrant
developed during training (probability cuing). In a subsequent, testing phase,
the target's location distribution became random. In addition, the training and
testing phases were based on different tasks. Probability cuing did not transfer
between visual search and a foraging-like task. However, it did transfer between
various types of visual search tasks that differed in stimuli and difficulty.
These data suggest that different visual search tasks share a common and
transferrable learned attentional bias. However, this bias is not shared by high
level, decision-making tasks such as foraging.
PMID- 25113855
TI - Contemporary sample stacking in analytical electrophoresis.
AB - This contribution is a methodological review of the publications about the topic
from the last 2 years. Therefore, it is primarily organized according to the
methods and procedures used in surveyed papers and the origin and type of sample
and specification of analytes form the secondary structure. The introductory part
about navigation in the architecture of stacking brings a brief characterization
of the various stacking methods, with the description of mutual links to each
other and important differences among them. The main body of the article brings a
survey of publications organized according to main principles of stacking and
then according to the origin and type of the sample. Provided that the paper
cited gave explicitly the relevant data, information about the BGE(s) used,
procedure, detector employed, and reached LOD and/or concentration effect is
given. The papers where the procedure used is a combination of diverse fragments
and parts of various stacking techniques are mentioned in a special section on
combined techniques. The concluding remarks in the final part of the review
evaluate present state of art and the trends of sample stacking in CE.
PMID- 25113856
TI - pANCA-vasculitis associated with rectal adenocarcinoma.
AB - We report the case of a 69-year-old male patient who was admitted for fever, dry
cough, recurrent sinusitis with epistaxis, anorexia with weight loss of 20 kg
over a 3-month period, myalgia, and mononeuritis multiplex. He was diagnosed with
pANCA/anti-MPO associated vasculitis and rectal adenocarcinoma. The tumor was
treated by surgical resection. Recurrence of vasculitis occurred during steroid
tapering which prompted us to add Mycophenolate mofetyl. A complete remission was
achieved. We conclude that in the present case the vasculitis was an independent
disease, not a paraneoplastic phenomenon. We discuss the value of different ANCA
serologies for diagnostics and follow-up, the epidemiology of vasculitis
associated with malignancy, and the concept of vasculitis as a paraneoplastic
syndrome.
PMID- 25113857
TI - Silencing the mob: disrupting quorum sensing as a means to fight plant disease.
AB - Bacteria are able to sense their population's density through a cell-cell
communication system, termed 'quorum sensing' (QS). This system regulates gene
expression in response to cell density through the constant production and
detection of signalling molecules. These molecules commonly act as auto-inducers
through the up-regulation of their own synthesis. Many pathogenic bacteria,
including those of plants, rely on this communication system for infection of
their hosts. The finding that the countering of QS-disrupting mechanisms exists
in many prokaryotic and eukaryotic organisms offers a promising novel method to
fight disease. During the last decade, several approaches have been proposed to
disrupt QS pathways of phytopathogens, and hence to reduce their virulence. Such
studies have had varied success in vivo, but most lend promising support to the
idea that QS manipulation could be a potentially effective method to reduce
bacterial-mediated plant disease. This review discusses the various QS-disrupting
mechanisms found in both bacteria and plants, as well as the different approaches
applied artificially to interfere with QS pathways and thus protect plant health.
PMID- 25113858
TI - Effect of glucosamine conjugation to zinc(II) complexes of a bis-pyrazole ligand:
syntheses, characterization and anticancer activity.
AB - The bis(3,5-dimethyl-1H- pyrazol-1yl)acetic acid (bdmpza) ligand was conjugated
with tert-butyl-N-(2-aminoethyl) carbonate, methyl-2-amino-4
(methylthio)butanoate and 1,3,4,6-tetra-O-acetyl-beta-d-glucosamine hydrochloride
via amide coupling method to form three ligands L1-L3 which were then reacted
with Zn(II) salts to form four zinc complexes (1-4). The complexes were
characterized by (1)H NMR, (13)C NMR, electrospray ionization mass spectrometry
(ESI-MS), FT-IR, CHN analyses. Complexes 1, 2 and 4 were also characterized by
single crystal X-ray diffraction. It was found that Zn(II) salts could
selectively remove the acetyl group from anomeric position leaving everything
else intact. The cytotoxicity studies of the ligand and the complexes showed that
the conjugation to acetylated glucosamine enhances cytotoxic ability although the
complexes become more hydrophilic. Cytotoxicity studies in human breast
adenocarcinoma (MCF-7), human cervical cancer (HeLa WT) and human lung
adenocarcinoma (A549) showed that the acetylated glucosamine conjugation to the
bis-pyrazole ligated Zn(II) complex led to 2-4 fold increase in cytotoxicity
(IC50 values ca. 57-80MUM) against HeLa WT and MCF-7 cell lines. The Zn(II)
complex bearing the acetylated glucosamine inhibits the cell cycle in the G2/M
phase of MCF-7 cell line. ICP-MS data shows more accumulation of Zn(II) inside
the cell upon use of complex 4 as compared to Zn(II) salts or the other presented
complexes. Further studies suggest that the mitochondrial transmembrane potential
changes in the presence of complex 4 and caspase-7 is activated by Zn(II) salts
but the activation is much more by complex 4 and hence there is apoptosis and
dose dependent chromatin condensation/nuclear fragmentation as observed by
microscopy.
PMID- 25113859
TI - CD36 and malaria: friends or foes? A decade of data provides some answers.
AB - The past 10 years have generated new insights into the complex interaction
between CD36 (cluster of differentiation 36) and malaria. These range from the
crystallization of the CD36 homolog, LIMPII (lysosomal integral membrane protein
II), permitting modeling of CD36 and its binding to diverse ligands, to cell
biology-based studies of CD36 and large population genetic studies assessing the
association of CD36 polymorphisms and malarial disease severity. Collectively
these lines of evidence indicate that a receptor other than CD36 is associated
with severity. CD36 plays an important role in innate immunity and in the
phagocytic uptake of multiple pathogens including malaria. CD36 polymorphisms
lack association with severity, and isolates that cause severe disease primarily
bind to endothelial protein C receptor (EPCR) rather than to CD36.
PMID- 25113860
TI - [Cameron ulcers: two clinical presentations of an unusual upper gastrointestinal
hemorrhage].
PMID- 25113861
TI - [MALT lymphoma of the gallbladder].
PMID- 25113863
TI - [A trichobezoar causing intestinal obstruction in an adolescent girl].
PMID- 25113862
TI - [Small bowel volvulus: an unusual radiological diagnosis in adults].
PMID- 25113864
TI - Evaluating the physical demands on firefighters using track-type stair descent
devices to evacuate mobility-limited occupants from high-rise buildings.
AB - The physical demands on firefighting personnel were investigated when using
different types of track-type stair descent devices designed for the emergency
evacuation of high rise buildings as a function of staircase width and evacuation
urgency. Twelve firefighters used five track-type stair descent devices during
simulated urgent and non-urgent evacuations. The devices were evaluated under two
staircase width conditions (1.12, and 1.32 m), and three devices were also
evaluated under a narrower staircase condition (0.91 m). Dependent measures
included electromyographic (EMG) data, spine motion, heart rates, Borg Scale
ratings, task durations and descent velocities. Stair descent speeds favored the
devices that had shorter fore/aft dimensions when moving through the landing. EMG
results indicated that there were tradeoffs due to design features, particularly
on the landings where the physical demands tended to be greater. On the landings,
devices that could be rolled on four wheels reduced the deltoid and bicep
activation levels.
PMID- 25113865
TI - Surgical management of primary hyperparathyroidism in older adults.
AB - OBJECTIVES: To compare the feasibility, safety, and outcome of parathyroidectomy
in the management of primary hyperparathyroidism (PHPT) in individuals aged 75
and older with that of those younger than 50. DESIGN: Retrospective chart review.
SETTING: Department of Endocrine Surgery, Hospital Paul Desbief (Marseille,
France). PARTICIPANTS: Individuals who underwent surgery from June 2005 to
February 2013 (N = 526) had a clinical examination and laboratory and imaging
assessments to diagnose PHPT. MEASUREMENTS: The clinical and biochemical
characteristics and surgery outcomes of individuals younger than 50 (n = 80) were
compared with the characteristics and outcomes of those aged 75 and older (n =
89). RESULTS: Most of the participants did not have any specific signs of PHPT,
and the diagnosis of PHPT was established in some participants during routine
clinical and laboratory examination. Nephrolithiasis and osteitis fibrosa cystica
were observed only in the younger group. Urinary calcium decreased with age. Nine
participants aged 75 and older did not undergo surgery (four declined, five had
medical contraindications). Conventional surgery through transverse cervicotomy
was used in the majority of participants. Cure rate was excellent (158/160), with
few and reversible minor complications. The coexistence of thyroid lesions was
significantly higher in the older (47.5%) than in the younger group (32.3%).
Nodules and multinodular goiters were removed in the majority of participants
during the parathyroidectomy procedure. CONCLUSION: With the exception of a few
cases with severe associated comorbidities, parathyroidectomy is safe and
curative and should be considered as first-line choice for older adult with PHPT.
PMID- 25113867
TI - [Current recommendations on optic neuritis].
AB - BACKGROUND: The diagnostics and therapy of optic neuritis are complex and require
interdisciplinary cooperation. AIM: Compact, up-to-date recommendations for the
clinician appear to be desirable. MATERIAL AND METHODS: A selective literature
search including the authors' professional experience was carried out. An
algorithm for the practical approach to optic neuritis was derived from the best
available evidence. RESULTS: Our recommendation distinguishes between compulsory
and optional investigations. Differential diagnostic cues with regard to atypical
optic neuritis and other optic neuropathies are shown. Standard therapy patterns
and means of escalation are suggested. Indications for referral are presented.
CONCLUSION: The algorithm suggested in this article provides ophthalmologists
with an effective orientation aid for the complete treatment procedure of optic
neuritis.
PMID- 25113868
TI - Control of the single-molecule magnet behavior of lanthanide-diarylethene
photochromic assemblies by irradiation with light.
AB - Lanthanide-based extended coordination frameworks showing photocontrolled single
molecule magnet (SMM) behavior were prepared by combining highly anisotropic
Dy(III) and Ho(III) ions with the carboxylato-functionalized photochromic
molecule 1,2-bis(5-carboxyl-2-methyl-3-thienyl)perfluorocyclopentene (H2 dae),
which acts as a bridging ligand. As a result, two new compounds of the general
formula [{Ln(III) 2 (dae)3 (DMSO)3 (MeOH)}?10 MeOH]n (M=Dy for 1 a and Ho for 2)
and two additional pseudo-polymorphs [{Dy(III) 2 (dae)3 (DMSO)3 (H2 O)}?x MeOH]n
(1 b) and [{Dy(III) 2 (dae)3 (DMSO)3 (DMSO)}?x MeOH]n (1 c) were obtained. All
four compounds have 2D coordination-layer topologies, in which carboxylate
bridged Ln2 units are linked together by dae(2-) anions into grid-like
frameworks. All four compounds exhibited a strong reversible photochromic
response to UV/Vis light. Moreover, both 1 a and 2 show field-induced SMM
behavior. The slow magnetic relaxation of 1 a is influenced by the
photoisomerization reaction leading to the observation of the cross-effect:
photocontrolled SMM behavior.
PMID- 25113866
TI - Direct effect of bevacizumab on glioblastoma cell lines in vitro.
AB - Bevacizumab is a humanized monoclonal antibody directed against the pro
angiogenic factor vascular and endothelial growth factor-A (VEGF-A) used in the
treatment of glioblastomas. Although most patients respond initially to this
treatment, studies have shown that glioblastomas eventually recur. Several non
mutually exclusive theories based on the anti-angiogenic effect of bevacizumab
have been proposed to explain these mechanisms of resistance. In this report, we
studied whether bevacizumab can act directly on malignant glioblastoma cells. We
observe changes in the expression profiles of components of the VEGF/VEGF-R
pathway and in the response to a VEGF-A stimulus following bevacizumab treatment.
In addition, we show that bevacizumab itself acts on glioblastoma cells by
activating the Akt and Erks survival signaling pathways. Bevacizumab also
enhances proliferation and invasiveness of glioblastoma cells in hyaluronic acid
hydrogel. We propose that the paradoxical effect of bevacizumab on glioblastoma
cells could be due to changes in the VEGF-A-dependent autocrine loop as well as
in the intracellular survival pathways, leading to the enhancement of tumor
aggressiveness. Investigation of how bevacizumab interacts with glioblastoma
cells and the resulting downstream signaling pathways will help targeting
populations of resistant glioblastoma cells.
PMID- 25113869
TI - Outcomes, impact on management, and costs of fungal eye disease consults in a
tertiary care setting.
AB - OBJECTIVE: To determine the frequency of clinical management changes resulting
from inpatient ophthalmic consultations for fungemia and the associated costs.
DESIGN: Retrospective case series. PARTICIPANTS: Three hundred forty-eight
inpatients at a tertiary care center between 2008 and 2012 with positive fungal
blood culture results, 238 of whom underwent an ophthalmologic consultation.
METHODS: Inpatient charts of all fungemic patients were reviewed. Costs were
standardized to the year 2014. The Student t test was used for all continuous
variables and the Pearson chi-square test was used for categorical variables.
MAIN OUTCOME MEASURES: Prevalence of ocular involvement, rate of change in
clinical management, mortality rate of fungemic patients, and costs of ophthalmic
consultation. RESULTS: Twenty-two (9.2%) of 238 consulted patients with fungemia
had ocular involvement. Twenty patients had chorioretinitis and 2 had
endophthalmitis. Only 9 patients (3.7%) had a change in management because of the
ophthalmic consultation. One patient underwent bilateral intravitreal injections.
Thirty percent of consulted patients died before discharge or were discharged to
hospice. The total cost of new consults was $36 927.54 ($204.19/initial level 5
visit and $138.63/initial level 4). The cost of follow-up visits was $13 655.44
($104.24/visit). On average, 26.4 patients were evaluated to find 1 patient
needing change in management, with an average cost of $5620.33 per change in 1
patient's management. CONCLUSIONS: Clinical management changes resulting from
ophthalmic consultation in fungemic patients were uncommon. Associated costs were
high for these consults in a patient population with a high mortality rate.
Together, these data suggest that the usefulness of routine ophthalmic
consultations for all fungemic patients is likely to be low.
PMID- 25113871
TI - Comprehensive two-dimensional liquid chromatographic analysis of anthocyanins.
AB - Anthocyanins are naturally occurring plant pigments whose accurate analysis is
hampered by their complexity and unique chromatographic behaviour associated with
on-column conversion reactions. This paper reports the evaluation of off-line
comprehensive two-dimensional liquid chromatography (LC*LC) for the analysis of
anthocyanins. Hydrophilic interaction chromatography (HILIC) was used in the
first dimension in combination with reversed phase liquid chromatography (RP-LC)
in the second dimension. For the selective detection of anthocyanins, diode array
detection was used, while high resolution quadrupole-time-of-flight mass
spectrometry (Q-TOF) was used for compound identification. As application, the
HILIC*RP-LC separation of diverse anthocyanins in blueberries, red radish, black
beans, red grape skins and red cabbage is demonstrated. Off-line HILIC*RP-LC
revealed information which could not be obtained by one-dimensional HPLC methods,
while the structured elution order for the anthocyanins simplifies compound
identification and facilitates the comparison of anthocyanin content of natural
products by means of contour plots.
PMID- 25113870
TI - Walking deficits and centrophobism in an alpha-synuclein fly model of Parkinson's
disease.
AB - Parkinson's disease (PD) is a movement neurodegenerative disorder, characterized
by bradykinesia, rigidity and tremor, constituting difficulties in walking and
abnormal gait. Previous research shows that Drosophila expressing human alpha
synuclein A30P (A30P) develop deficits in geotaxis climbing; however, geotaxis
climbing is a different movement modality from walking. Whether A30P flies would
exhibit abnormal walking in a horizontal plane, a measure more relevant to PD, is
not known. In this study, we characterized A30P fly walking using a high-speed
camera and an automatic behavior tracking system. We found that old but not young
A30P flies exhibited walking abnormalities, specifically decreased total moving
distance, distance per movement, velocity, angular velocity and others, compared
with old control flies. Those features match the definition of bradykinesia.
Multivariate analysis further suggested a synergistic effect of aging and A30P,
resulting in a distinct pattern of walking deficits, as seen in aged A30P flies.
Psychiatric problems are common in PD patients with anxiety affecting 40-69% of
patients. Central avoidance is one assessment of anxiety in various animal
models. We found old but not young A30P flies exhibited increased centrophobism,
suggesting possible elevated anxiety. Here, we report the first quantitative
measures of walking qualities in a PD fly model and propose an alternative
behavior paradigm for evaluating motor functions apart from climbing assay.
PMID- 25113872
TI - In situ derivatization combined to automated microextraction by packed sorbents
for the determination of chlorophenols in soil samples by gas chromatography mass
spectrometry.
AB - A method based on the coupling of in situ extraction and derivatization of
chlorophenols (CPs) (2-chlorophenol, 4-chloro-3-methylphenol, 2,4-dichlorophenol,
and 2,4,6-trichlorophenol) from soils, accomplishing their preconcentration by
means of automated microextraction by packed sorbent (MEPS), is proposed. After
extraction and acylation of the chlorophenols in aqueous medium, the liquid phase
obtained is subjected to the MEPS procedure. The QuEChERS (Quick, Easy, Cheap,
Effective, Rugged and Safe) and MEPS techniques were compared and the results
confirmed the preconcentration carried out with MEPS. The existence of a matrix
effect was checked and the analytical characteristics of the method were
determined in a soil sample. The method provided good linearity (from 1 to
12MUgkg(-1)), together with good repeatability and reproducibility values (RSD
equal to or less than 10%). The limits of detection were in the 0.118-0.894MUgkg(
1) range. A certified reference material was applied to validate the proposed
methodology.
PMID- 25113873
TI - Optimum pH for the determination of bisphenols and their corresponding diglycidyl
ethers by gas chromatography-mass spectrometry. Migration kinetics of bisphenol A
from polycarbonate glasses.
AB - This paper presents, on the one hand, the study of the influence of the pH of the
medium on the determination of bisphenol F (BPF), bisphenol A (BPA) and their
corresponding diglycidyl ethers (BFDGE and BADGE, respectively) by GC-MS after a
solid-phase extraction step, using BPA-d16 as internal standard and Parallel
Factor Analysis (PARAFAC) decomposition as a multi-way tool for the unequivocal
identification and quantification of the four analytes. As the structure of both
BFDGE and BADGE has two 2,3-epoxypropoxy groups that can undergo an acid- or base
catalyzed ring-opening via nucleophilic substitution reactions, several samples
spiked with the four analytes were set to different pH values between 2 and 12.
The best results were obtained in the pH region 8-10, being 9 the most suitable
value. Coelution of interferents was overcome using the PARAFAC decomposition;
otherwise, the presence of some analytes could not have been ensured according to
the regulations currently in force. Secondly, the release of BPA from
polycarbonate glasses into food simulant D1 (ethanol 50% (v/v)) over time was
studied through seven migration tests and the differences found in this migration
process with the incubation temperature (50 and 70 degrees C) were evaluated. A
nonlinear regression was used to fit the experimental data following an
exponential relation between the concentration of BPA transferred from every
glass and the respective migration test. None of the quantities of BPA released
exceeded the specific migration limit of 0.6mgkg(-1) laid down for this compound
in the Commission Regulation (EU) No 10/2011, so the compliance of the glasses
evaluated was ensured. The average recovery percentages of the four analytes at a
fortification level of 800ngL(-1) ranged from 50.14 to 92.75%. The detection
capability (CCbeta) of the method for BPA was 2.60MUgL(-1) for n=2 replicates,
with probabilities of false positive and false negative fixed at 0.05.
PMID- 25113874
TI - Photoactivated cytotoxicity of ferrocenyl-terpyridine oxovanadium(IV) complexes
of curcuminoids.
AB - Oxovanadium(IV) complexes, viz. [VO(Fc-tpy)(Curc)](ClO4) (1), [VO(Fc
tpy)(bDHC)](ClO4) (2), [VO(Fc-tpy)(bDMC)](ClO4) (3) and [VO(Ph-tpy)(Curc)](ClO4)
(4), of 4'-ferrocenyl-2,2':6',2"-terpyridine (Fc-tpy) and 4'-phenyl-2,2':6',2"
terpyridine (Ph-tpy) and monoanionic curcumin (Curc), bis-dehydroxycurcmin (bDHC)
and bis-demethoxycurcumin (bDMC) were prepared, characterized and their photo
induced DNA cleavage activity and photocytotoxicity in visible light studied. The
ferrocenyl complexes 1-3 showed an intense metal-to-ligand charge transfer band
near 585 nm in DMF and displayed Fc(+)/Fc and V(IV)/V(III) redox couples near
0.65 V and -1.05 V vs. SCE in DMF-0.1 M TBAP. The complexes as avid binders to
calf thymus DNA showed significant photocleavage of plasmid DNA in red light of
647 nm forming OH radicals. The complexes showed photocytotoxicity in HeLa and
Hep G2 cancer cells in visible light of 400-700 nm with low dark toxicity. ICP-MS
and fluorescence microscopic studies exhibited significant cellular uptake of the
complexes within 4 h of treatment with complexes. The treatment with complex 1
resulted in the formation of reactive oxygen species inside the HeLa cells which
was evidenced from the DCFDA assay.
PMID- 25113875
TI - Indole-3-ethylsulfamoylphenylacrylamides: potent histone deacetylase inhibitors
with anti-inflammatory activity.
AB - A series of 2-methyl-1H-indol-3-ethylsulfamoylphenylacrylamides based on LBH589
PXD101 core have been synthesized and evaluated for their histone deacetylase
(HDAC) inhibitory and anti-inflammatory activity. In vitro, compounds 9-12 show
2.6-fold better HDAC inhibition and 3-fold better IL-6 suppression compared to
LBH589.HCl (1.HCl). Furthermore, these compounds did not show apparent cell
viability suppression on macrophages while in contrast, treatment with 1.HCl
resulted in significant reduction in cell viability as demonstrated by an MTT
assay. Repressed expression of iNOS, COX-2 and reduced phosphorylation of p65
revealed the inhibitory effect of these analogues on inflammatory mediator
release which is related to inhibited NF-KB signals. (N-Hydroxy-3-{3-[2-(2-methyl
1H-indol-3-yl)-ethylsulfamoyl]-phenyl}-acrylamide) (9), exhibited ability
superior to that of 1.HCl, was able to reduce carrageenan-induced acute
inflammation in an animal model. Compounds 9-12 have potential anti-inflammatory
activity and compound 9 can serve as lead compound for further development.
PMID- 25113876
TI - Improvement of antibacterial activity of some sulfa drugs through linkage to
certain phthalazin-1(2H)-one scaffolds.
AB - RAB1 5 is a lead antibacterial agent in which trimethoprim is linked to
phthalazine moiety. Similarly, our strategy in this research depends on the
interconnection between some sulfa drugs and certain phthalazin-1(2H)-one
scaffolds in an attempt to enhance their antibacterial activity. This approach
was achieved through the combination of 4-substituted phthalazin-1(2H)-ones 9a, b
or 14a, b with sulfanilamide 1a, sulfathiazole 1b or sulfadiazine 1c through
amide linkers 6a, b to produce the target compounds 10a-d and 15a-e,
respectively. The antibacterial activity of the newly synthesized compounds
showed that all tested compounds have antibacterial activity higher than that of
their reference sulfa drugs 1a-c. Compound 10c represented the highest
antibacterial activity against Gram-positive bacteria Streptococcus pneumonia and
Staphylococcus aureus with MIC = 0.39 MUmol/mL. Moreover, compound 10d displayed
excellent antibacterial activity against Gram-negative bacteria Escherichia coli
and Salmonella typhimurium with MIC = 0.39 and 0.78 MUmol/mL, respectively.
PMID- 25113877
TI - Design, synthesis and biological evaluation of novel 1-hydroxyl-3-aminoalkoxy
xanthone derivatives as potent anticancer agents.
AB - A series of novel 1-hydroxyl-3-aminoalkoxy xanthone derivatives were designed,
synthesized and evaluated for in vitro anticancer activity against four selected
human cancer cell lines (nasopharyngeal neoplasm CNE, liver cancer BEL-7402,
gastric cancer MGC-803, lung adenocarcinoma A549). Most of the synthesized
compounds exhibit effective cytotoxic activity against the four tested cancer
cell lines with the IC50 values at micromolar concentration level. Some
preliminary structure-activity relationships were also discussed. In this series
of derivatives, compound 3g shows excellent broad spectrum anticancer activity
with IC50 values ranging from 3.57 to 20.07 MUM. The in vitro anticancer activity
effect and action mechanism of compound 3g on human gastric carcinoma MGC-803
cell were further investigated. The results showed that compound 3g exhibits dose
and time-dependent anticancer effects on MGC-803 cells through apoptosis, which
might be associated with its decreasing intracellular calcium and the
mitochondrial membrane potential.
PMID- 25113878
TI - Synthesis and evaluation of novel podophyllotoxin derivatives as potential
antitumor agents.
AB - Cancer multidrug resistance (MDR) is a common cause of treatment failure in
cancer patients. Increased expression of permeability glycoprotein (P-gp), which
is also known as MDR-1, is the main cause of multidrug resistance.
Podophyllotoxin derivatives hold great promise in the battle to overcome
multidrug resistance, as they can induce cytotoxicity through multiple
mechanisms. Here, we synthesized sixteen novel podophyllotoxin derivatives and
evaluated their cytotoxicities in human cancer cell lines, HeLa, K562 and
K562/A02. Some of these compounds were more potent than etoposide, a clinically
relevant inhibitor of DNA repair enzymes. In particular, compound 5p exhibited
the most potent activity toward drug-resistant K562/A02 cells, as it robustly
inhibited tumor cell proliferation and induced apoptosis. Furthermore,
preliminary investigation suggested that 5p inhibited the expression of MDR-1 in
K562/A02 cells more effectively than etoposide.
PMID- 25113879
TI - Synthesis and bioevaluation of 2-phenyl-4-methyl-1,3-selenazole-5-carboxylic
acids as potent xanthine oxidase inhibitors.
AB - A series of 2-phenyl-4-methyl-1,3-selenazole-5-carboxylic acid derivatives (8a-f,
9a-m) were synthesized and evaluated for inhibitory activity against xanthine
oxidase in vitro. Structure-activity relationship analyses have also been
presented. Most of the target compounds exhibited potency levels in the nanomolar
range. Compound 9e emerged as the most potent xanthine oxidase inhibitor (IC50 =
5.5 nM) in comparison to febuxostat (IC50 = 18.6 nM). Steady-state kinetics
measurements with the bovine milk enzyme indicated a mixed type inhibition with
Ki and Ki' values of 0.9 and 2.3 nM, respectively. A molecular modeling study on
compounds 9e was performed to gain an insight into its binding mode with xanthine
oxidase, and to provide the basis for further structure-guided design of new non
purine xanthine oxidase inhibitors related with 2-phenyl-4-methyl-1,3-selenazole
5-carboxylic acid scaffold.
PMID- 25113881
TI - Experimental and economical evaluation of bioconversion of forest residues to
biogas using organosolv pretreatment.
AB - The methane potential of forest residues was compared after applying organic
solvent, i.e., acetic acid, ethanol, and methanol pretreatments using batch
anaerobic digestion (AD). The pretreatments were performed at 190 degrees C with
50% (V/V) organic solvent for 60 min. The accumulated methane yields after 40
days of AD from pretreated forest residues were between 0.23 and 0.34 m(3) CH4/kg
VS, which shows a significant improvement compared to 0.05 m(3) CH4/kg VS, from
untreated forest residues. These improvements count up to 50% increase in the
methane yields from the pretreated substrates based on expected theoretical yield
from carbohydrates. Among the organic solvents, pretreatments with acetic acid
and ethanol led to highest methane yields, i.e., over 0.30 m(3) CH4/kg VS.
However, techno-economical evaluation showed, pretreatment with methanol was more
viable financially. The capital investments of the plant operating 20,000 tons of
forest residues varied between 56 and 60 million USD, which could be recovered in
less than 8 years of operation.
PMID- 25113882
TI - Effect of liquefaction temperature on hydroxyl groups of bio-oil from loblolly
pine (Pinus taeda).
AB - Loblolly pine was liquefied with ethylene glycol at 100, 150, 200 and 250
degrees C in order to analyze the effect of liquefaction temperature on hydroxyl
groups of bio-oil, and to determine the source and variation of hydroxyl groups.
The optimum temperature was found to be 150-200 degrees C. Hydroxyl number (OHN)
of the bio-oil was ranged from 632 to 1430 mg KOH/g. GC-MS analysis showed that
70-90% of OHN was generated from unreacted EG. (31)P NMR analysis showed that the
majority of hydroxyl groups were aliphatic, and none of the bio-oil exhibited any
detectable hydroxyl groups from phenolic sources. Finally, it was found that all
bio-oils were stable in terms of OHN for 2 months when stored at -10 degrees C.
PMID- 25113883
TI - Fast pyrolysis product distribution of biopretreated corn stalk by methanogen.
AB - After pretreated by methanogen for 5, 15 and 25 days, corn stalk (CS) were
pyrolyzed at 250, 300, 350, 400, 450 and 500 degrees C by Py-GC/MS and product
distribution in bio-oil was analyzed. Results indicated that methanogen
pretreatment changed considerably the product distribution: the contents of sugar
and phenols increased; the contents of linear carbonyls and furans decreased; the
contents of linear ketones and linear acids changed slightly. Methanogen
pretreatment improved significantly the pyrolysis selectivity of CS to phenols
especially 4-VP. At 250 degrees C, the phenols content increased from 42.25% for
untreated CS to 79.32% for biopretreated CS for 5 days; the 4-VP content
increased from 28.6% to 60.9%. Increasing temperature was contributed to convert
more lignin into 4-VP, but decreased its content in bio-oil due to more other
chemicals formed. The effects of biopretreatment time on the chemicals contents
were insignificant.
PMID- 25113884
TI - Cationic polymers for successful flocculation of marine microalgae.
AB - Flocculation of microalgae is a promising technique to reduce the costs and
energy required for harvesting microalgae. Harvesting marine microalgae requires
suitable flocculants to induce the flocculation under marine conditions. This
study demonstrates that cationic polymeric flocculants can be used to harvest
marine microalgae. Different organic flocculants were tested to flocculate
Phaeodactylum tricornutum and Neochloris oleoabundans grown under marine
conditions. Addition of 10 ppm of the commercial available flocculants Zetag 7557
and Synthofloc 5080H to P. tricornutum showed a recovery of, respectively, 98% +/
2.0 and 94% +/- 2.9 after flocculation followed by 2h sedimentation. Using the
same flocculants and dosage for harvesting N. oleoabundans resulted in a recovery
of 52% +/- 1.5 and 36% +/- 11.3. This study shows that cationic polymeric
flocculants are a viable option to pre-concentrate marine cultivated microalgae
via flocculation prior to further dewatering.
PMID- 25113886
TI - Identification and analysis of ADP-ribosylated proteins.
AB - The analysis of ADP-ribosylated proteins is a challenging task, on the one hand
because of the diversity of the target proteins and the modification sites, on
the other hand because of the particular problems posed by the analysis of ADP
ribosylated peptides. ADP-ribosylated proteins can be detected in in vitro
experiments after the incorporation of radioactively labeled or chemically
modified ADP-ribose. Endogenously ADP-ribosylated proteins may be detected and
enriched by antibodies directed against the ADP-ribosyl moiety or by ADP-ribosyl
binding macro domains. The determination of the exact attachment site of the
modification, which is a prerequisite for the understanding of the specificity of
the various ADP-ribosyl transferases and the structural consequences of ADP
ribosylation, necessitates the proteolytic cleavage of the proteins. The
resulting peptides can afterwards be enriched either by IMAC (using the affinity
of the pyrophosphate group for heavy metal ions) or by immobilized boronic acid
beads (using the affinity of the vicinal ribose hydroxy groups for boronic acid).
The identification of the modified peptides usually requires tandem mass
spectrometric measurements. Problems that hamper the mass spectrometric analysis
by collision-induced decay (CID) can be circumvented either by the application of
different fragmentation techniques (electron transfer or electron capture
dissociation; ETD or ECD) or by enzymatic cleavage of the ADP-ribosyl group to
ribosyl-phosphate.
PMID- 25113887
TI - Will new insights into neural networks help us improve our models of suicidal
behavior?
PMID- 25113885
TI - Combination of glucosamine and low-dose cyclosporine for atopic dermatitis
treatment: a randomized, placebo-controlled, double-blind, parallel clinical
trial.
AB - Our recent pilot study showed better outcomes using a combination of low-dose
cyclosporine and glucosamine than cyclosporine alone in the treatment of atopic
dermatitis (AD). Here, a randomized, placebo-controlled, double-blind, parallel
designed study was planned to compare the efficacy and safety of low-dose
cyclosporine and glucosamine combination to low-dose cyclosporine alone for the
treatment of patients with moderate to severe AD. AD patients with a Severity
Scoring of Atopic Dermatitis (SCORAD) index >= 30 were randomly assigned in a 1:1
ratio to receive either cyclosporine 2 mg/kg and glucosamine 25 mg/kg (group A)
or cyclosporine and placebo (group B) for 8 weeks. SCORAD indices, serum levels
of chemokine ligand 17 and interleukin-31, eosinophil counts, and blood
cyclosporine levels were examined before and after treatment. The SCORAD indices
for group A (n = 19) were significantly reduced after the treatment and a
significant correlation between the changes in the SCORAD indices and changes in
the serum levels of chemokine ligand 17, but not interleukin-31, was detected.
Glucosamine combined with cyclosporine did not increase adverse events and serum
cyclosporine levels compared with cyclosporine alone. Therefore, combination of
low-dose cyclosporine and glucosamine may be useful to allow the long-term use of
cyclosporine in the treatment of patients with moderate to severe AD.
PMID- 25113888
TI - Exploring prospective predictors of completed suicides: evidence from the general
social survey.
AB - BACKGROUND: This study was based on over 30,000 respondents who completed General
Social Surveys between 1978 and 2002. AIMS: We approached these respondents
prospectively, comparing and contrasting the responses of those who subsequently
died by suicide (N = 141) with those who died from all other causes (N = 9,115).
METHOD: We employed chi-square and logistic regression analyses of important
demographic confounders to test for statistically significant differences between
suicide decedents and all other decedents. RESULTS: Suicide decedents died on
average 2 years sooner than all other decedents. When covariates of age and
gender were applied, suicide decedents exhibited greater acceptance of suicide
for dealing with various adverse life circumstances, were more likely to have
been the gun owners in their households, lived in regions where gun ownership was
more commonplace, and held less strong religious beliefs and less of a belief of
an afterlife. CONCLUSION: The observed affinity between attitudes of suicide
acceptability and completed suicide suggests a potential for creating a
meaningful assessment tool to identify those positioned at the extreme end of the
suicide risk continuum.
PMID- 25113889
TI - The rate of fatality and demographic characteristics associated with various
suicide methods: a community-based study in Northern Taiwan.
AB - BACKGROUND: Understanding lethality and risk factors of suicide methods is an
initial step in suicide prevention. AIMS: To investigate the fatality rate and
demographic characteristics of various suicide methods. METHOD: This study
enrolled consecutive individuals with episodes of suicide attempts registered in
a surveillance database in a city with a high rate of suicide mortality in
Taiwan, from January 1, 2006, to December 31, 2010. In total, 3,089 suicide
attempt events (including 2,583 nonfatal suicides and 506 completed suicides)
occurred during the study period. RESULTS: Overall, the fatality rate of suicides
was 16.4%. Charcoal burning accounted for the most suicide deaths (37.6%), with a
fatality rate of 50.1%. Suicide by hanging carried the highest fatality rate
(81.2%). Males tended to choose more lethal methods and had higher fatality rates
compared with females. Elders and married persons were less likely to attempt
suicide by charcoal burning. The case fatality ratio increased along with age
among suicide attempts, but not in those using charcoal burning. CONCLUSION: The
choice of suicide methods and lethality might be influenced by one's demographic
characteristics. RESULTS from this study may provide clues for establishing
suicide prevention strategies such as restricting access to common lethal suicide
methods in the high-risk group.
PMID- 25113890
TI - Shadows from the past: the situated meaning of being suicidal among depressed
older people living in the community.
AB - BACKGROUND: Most depressed older people in a suicidal state have mixed feelings,
where the wish to live and the wish to die wage a battle. AIMS: To explore and
describe depressed older people's experiences of being suicidal and their search
for meaning. METHOD: Data were collected from 29 participants resident in the
Rogaland and Vestfold districts of Norway, by means of individual interviews,
after which a thematic analysis was performed. RESULTS: For the participants in
this study, the lived experiences of the situated meaning of survival after being
suicidal comprised a main theme - "shadows from the past" - and two themes -
"feeling that something inside is broken" and "a struggle to catch the light."
CONCLUSION: Mental health-care professionals might be able to reduce the risk of
suicide and perturbation by helping depressed older people to explore, resolve,
and ultimately come to terms with their unresolved historical issues. Additional
valuable strategies in primary care settings include encountering patients
frequently, monitoring adherence to care plans, and providing support to address
the source of emotional pain and distress.
PMID- 25113891
TI - Ethnic differences in self-poisoning across South London.
AB - BACKGROUND: Self-poisoning (overdose) is the commonest form of self-harm cases
presenting to acute secondary care services in the UK, where there has been
limited investigation of self-harm in black and minority ethnic communities.
London has the UK's most ethnically diverse areas but presents challenges in
resident-based data collection due to the large number of hospitals. AIMS: To
investigate the rates and characteristics of self-poisoning presentations in two
central London boroughs. METHOD: All incident cases of self-poisoning
presentations of residents of Lambeth and Southwark were identified over a 12
month period through comprehensive acute and mental health trust data collection
systems at multiple hospitals. Analysis was done using STATA 12.1. RESULTS: A
rate of 121.4/100,000 was recorded across a population of more than half a
million residents. Women exceeded men in all measured ethnic groups. Black women
presented 1.5 times more than white women. Gender ratios within ethnicities were
marked. Among those aged younger than 24 years, black women were almost 7 times
more likely to present than black men were. CONCLUSION: Self-poisoning is the
commonest form of self-harm presentation to UK hospitals but population-based
rates are rare. These results have implications for formulating and managing risk
in clinical services for both minority ethnic women and men.
PMID- 25113892
TI - History of suicide attempts in adults with Asperger syndrome.
AB - BACKGROUND: Individuals with Asperger syndrome (AS) may be at higher risk for
attempting suicide compared to the general population. AIMS: This study examines
the issue of suicidality in adults with AS. METHOD: An online survey was
completed by 50 adults from across Ontario. The sample was dichotomized into
individuals who had attempted suicide (n = 18) and those who had not (n = 32). We
examined the relationship between predictor variables and previous attempts, and
compared the services that both groups are currently receiving. RESULTS: Over 35%
of individuals with AS reported that they had attempted suicide in the past.
Individuals who attempted suicide were more likely to have a history of
depression and self-reported more severe autism symptomatology. Those with and
without a suicidal history did not differ in terms of the services they were
currently receiving. This study looks at predictors retrospectively and cannot
ascertain how long ago the attempt was made. Although efforts were made to obtain
a representative sample, there is the possibility that the individuals surveyed
may be more or less distressed than the general population with AS. CONCLUSION:
The suicide attempt rate in our sample is much higher than the 4.6% lifetime
prevalence seen in the general population. These findings highlight a need for
more specialized services to help prevent future attempts and to support this
vulnerable group.
PMID- 25113893
TI - Lipophilic statin use and suicidal ideation in a sample of adults with mood
disorders.
AB - BACKGROUND: Mood disorders are associated with a high risk of suicide. Statin
therapy has been implicated in this relationship. AIMS: To further clarify
reported associations between suicide and cholesterol in mental health
conditions, we conducted an analysis of dietary, clinical, and suicidal ideation
measures in community-living adults with mood disorders. METHOD: Data were used
from a cross-sectional study of a randomly selected community-based sample (> 18
years; n = 97) with verified mood disorders. Dietary (e.g., fat, iron, vitamin
intakes), clinical (e.g., current depression and mania symptoms, medications),
and sociodemographic (age, sex, and income) measures were analyzed using
bivariate statistics and Poisson regression with robust variance. RESULTS:
Participants were predominantly female (71.1%) with bipolar disorder (59.8%);
almost one-third (28.9%) were taking lipophilic statins. The prevalence of
suicidal ideation was more than 2.5 times in those taking statins, PR = 2.59, 95%
CI 1.27-5.31, p < .05. The prevalence ratio for suicidal ideation was 1.10, 95%
CI 1.06-1.15, p < .001, for each unit increase in mania symptom scores. No
associations between suicidal ideation and dietary intake measures were
identified. CONCLUSION: Individuals with mood disorders may be susceptible to
neuropsychiatric effects of cholesterol-lowering drugs, which warrants further
research.
PMID- 25113897
TI - Improving prediction of binge episodes by modelling chronicity of dietary
restriction.
AB - This study evaluates the influences of chronicity of, and time lag between,
dietary restriction and binge outcome for predicting binge episode onset. Sixty
two women aged 18 to 40 years old completed an online survey at random intervals
seven times daily for a 7-day period. Participants self-reported engagement in
dietary restriction and/or binging, and temptation to binge. Consecutive
instances of reported dietary restriction better predicted subsequent binges than
single instances. As the time lag between the first report of dietary restriction
and binge onset increased, a clear linear trend emerged, such that the value of
restriction for predicting binges increased with the number of consecutive
assessments in which they reported dietary restriction. A similar pattern was
found when predicting temptation to binge. Present findings suggest that duration
of restriction is a crucial determinant of binge onset. These findings have
implications for clinical practice by highlighting the time course from dietary
restriction to binging.
PMID- 25113896
TI - Influence of RNA extraction methods and library selection schemes on RNA-seq
data.
AB - BACKGROUND: Gene expression analysis by RNA sequencing is now widely used in a
number of applications surveying the whole transcriptomes of cells and tissues.
The recent introduction of ribosomal RNA depletion protocols, such as RiboZero,
has extended the view of the polyadenylated transcriptome to the poly(A)-
fraction of the RNA. However, substantial amounts of intronic transcriptional
activity has been reported in RiboZero protocols, raising issues regarding their
potential nuclear origin and the impact on the actual sequence depth in exonic
regions. RESULTS: Using HEK293 human cells as source material, we assessed here
the impact of the two commonly used RNA extraction methods and of the library
construction protocols (rRNA depletion versus mRNA) on 1) the relative abundance
of intronic reads and 2) on the estimation of gene expression values. We
benchmarked the rRNA depletion-based sequencing with a specific analysis of the
cytoplasmic and nuclear transcriptome fractions, suggesting that the large
majority of the intronic reads correspond to unprocessed nuclear transcripts
rather than to independent transcriptional units. We show that Qiagen or TRIzol
extraction methods retain differentially nuclear RNA species, and that
consequently, rRNA depletion-based RNA sequencing protocols are particularly
sensitive to the extraction methods. CONCLUSIONS: We could show that the
combination of Trizol-based RNA extraction with rRNA depletion sequencing
protocols led to the largest fraction of intronic reads, after the sequencing of
the nuclear transcriptome. We discuss here the impact of the various strategies
on gene expression and alternative splicing estimation measures. Further, we
propose guidelines and a double selection strategy for minimizing the expression
biases, without loss of information.
PMID- 25113899
TI - Temporal trends in non-stricturing and non-penetrating behaviour at diagnosis of
Crohn's disease in Orebro, Sweden: a population-based retrospective study.
AB - BACKGROUND AND AIM: The incidence of Crohn's disease (CD) is continuing to rise
in several countries and in others it appears to have already levelled off after
a period of increase. We updated our previous population-based study, by re
extraction of all information on patients diagnosed with CD between 1963 and
2010. Our aim was to assess temporal trends in incidence, prevalence and disease
phenotype at diagnosis. METHODS: Patients of all ages with a potential diagnosis
of CD were identified retrospectively by evaluation of medical notes of all
current and previous patients at the colitis clinic, Orebro University Hospital
amended by computerised search in the inpatient, outpatient, primary care and
histopathological records. Diagnosis was confirmed by subsequent evaluation of
medical notes. Disease phenotype was defined according to the Montreal
classification. RESULTS: The incidence increased over time, especially among
Crohn's disease, A1 and A3. SaTScan model revealed a statistically significant
high incidence during 1991-2010 (p=0.0001). The median age at diagnosis increased
from 28 (3-79) years to 37 (5-87) years (p=0.0002). The point prevalence
increased from 21/10(5) (14-32) in 1965 to 267/10(5) (244-291) in 2010. Non
stricturing and non-penetrating disease at diagnosis increased from 12.5% in 1963
1965 to 82.3% in 2006-2010 (p<0.0001). CONCLUSION: The incidence of CD increased
over time, although it seemed to be plateauing during the most recent decades. A
striking increase in non-stricturing, non-penetrating disease at diagnosis was
observed, suggesting earlier diagnosis or phenotypic change. The observed point
prevalence in 2010 is among the highest reported.
PMID- 25113900
TI - Kinetic analysis of mechanochemical chain scission of linear
poly(phthalaldehyde).
AB - The kinetics of mechanochemical chain scission of poly(phthalaldehyde) (PPA) are
investigated. Ultrasound-induced cavitation is capable of causing chain scission
in the PPA backbone that ultimately leads to rapid depolymerization of each
resulting polymer fragment when above the polymer's ceiling temperature (Tc ). An
interesting feature of the mechanochemical breakdown of PPA is that "half-chain"
daughter fragments are not observed, since the depolymerization is rapid
following chain scission. These features facilitate the determination of rate
constants of activation for multiple molecular weights from a single sonication
experiment. Additionally, the degradation kinetics are modified with chain-end
trapping agents through variation of the nature and amount of small molecule
nucleophile or electrophile.
PMID- 25113901
TI - Early bovine embryos regulate oviduct epithelial cell gene expression during in
vitro co-culture.
AB - In mammals, the oviduct may participate to the regulation of early embryo
development. In vitro co-culture of early bovine embryos with bovine oviduct
epithelial cells (BOEC) has been largely used to mimic the maternal environment.
However, the mechanisms of BOEC action have not been clearly elucidated yet. The
aim of this study was to determine the response of BOEC cultures to the presence
of developing bovine embryos. A 21,581-element bovine oligonucleotide array was
used compare the gene expression profiles of confluent BOEC cultured for 8 days
with or without embryos. This study revealed 34 differentially expressed genes
(DEG). Of these 34 genes, IFI6, ISG15, MX1, IFI27, IFI44, RSAD2, IFITM1, EPSTI1,
USP18, IFIT5, and STAT1 expression increased to the greatest extent due to the
presence of embryos with a major impact on antiviral and immune response. Among
the mRNAs at least 25 are already described as induced by interferons. In
addition, transcript levels of new candidate genes involved in the regulation of
transcription, modulation of the maternal immune system and endometrial
remodeling were found to be increased. We selected 7 genes and confirmed their
differential expression by quantitative RT-PCR. The immunofluorescence imaging of
cellular localization of STAT1 protein in BOEC showed a nuclear translocation in
the presence of embryos, suggesting the activation of interferon signaling
pathway. This first systematic study of BOEC transcriptome changes in response to
the presence of embryos in cattle provides some evidences that these cells are
able to adapt their transcriptomic profile in response to embryo signaling.
PMID- 25113898
TI - Patient and physician views on the quality of care in inflammatory bowel disease:
results from SOLUTION-1, a prospective IG-IBD study.
AB - INTRODUCTION: Remarkable differences in quality of care (QoC) might be observed
in different countries, affecting quality of life of inflammatory bowel disease
(IBD) patients. The aim of this study was to assess patient and physician
perceptions of the QoC in Italy. METHODS: A multicentre observational study on
the quality of care in IBD (SOLUTION-1) was conducted in 36 IG-IBD (Italian Group
for Inflammatory Bowel Disease) centres in Italy. The QUOTE-IBD (Quality of Care
Through the Patient's Eyes) questionnaire was administered to IBD patients and to
the attending physicians. The Quality Impact (QI) score summarises the QUOTE-IBD
questionnaire, and a QI >9 is considered satisfactory. RESULTS: Nine-hundred
ninety-two patients and 75 physicians completed the QUOTE-IBD questionnaire. The
patients scored the domains of competence (9.47 vs. 8.55) and costs (9.54 vs.
8.26) higher that the physicians, while information (9.31 vs. 9.43) and
continuity of care (8.40 vs. 9.01) were scored lower. The QI score was rated
worse by physicians with less experience (<12 years) with regard to competence
(8.0 vs. 9.01), courtesy (8.12 vs. 10.0) and autonomy (8.97 vs. 10.0). Physicians
considered the cost domain unsatisfactory. CONCLUSIONS: Healthcare was rated as
satisfactory overall for Italian patients and physicians. The physicians
underestimate their competence and consider the cost of medical management
unsatisfactory. The patients are more critical regarding the continuity of care
and information. Country-specific data on QoC allow local governments to allocate
resources more effectively.
PMID- 25113904
TI - Patchwork structure-function analysis of the Sendai virus matrix protein.
AB - Paramyxoviruses contain a bi-lipidic envelope decorated by two transmembrane
glycoproteins and carpeted on the inner surface with a layer of matrix proteins
(M), thought to bridge the glycoproteins with the viral nucleocapsids. To
characterize M structure-function features, a set of M domains were mutated or
deleted. The genes encoding these modified M were incorporated into recombinant
Sendai viruses and expressed as supplemental proteins. Using a method of
integrated suppression complementation system (ISCS), the functions of these M
mutants were analyzed in the context of the infection. Cellular membrane
association, localization at the cell periphery, nucleocapsid binding, cellular
protein interactions and promotion of viral particle formation were characterized
in relation with the mutations. At the end, lack of nucleocapsid binding go
together with lack of cell surface localization and both features definitely
correlate with loss of M global function estimated by viral particle production.
PMID- 25113902
TI - Marital conflict in early childhood and adolescent disordered eating: emotional
insecurity about the marital relationship as an explanatory mechanism.
AB - Disordered eating behaviors, including frequent dieting, unhealthy weight control
behaviors (e.g., vomiting and skipping meals for weight loss) and binge eating
are prevalent among adolescents. While negative, conflict-ridden family
environments have long been implicated as problematic and a contributing factor
to the development of disordered eating, few studies have examined the influence
of marital conflict exposure in childhood to understand the development of these
behaviors in adolescence. The current study investigates the impact of marital
conflict, children's emotional insecurity about the marital relationship, and
disordered eating behaviors in early adolescence in a prospective, longitudinal
study of a community sample of 236 families in Midwest and Northeast regions of
the U.S. Full structural mediation analyses utilizing robust latent constructs of
marital conflict and emotional insecurity about the marital relationship, support
children's emotional insecurity as an explanatory mechanism for the influence of
marital conflict on adolescent disordered eating behaviors. Findings are
discussed with important implications for the long-term impact of marital
conflict and the development of disordered eating in adolescence.
PMID- 25113905
TI - Functional characterization of Autographa californica multiple
nucleopolyhedrovirus gp16 (ac130).
AB - To investigate the function of Autographa californica multiple
nucleopolyhedrovirus (AcMNPV) gp16, multiple gp16-knockout and repair mutants
were constructed and characterized. No obvious difference in productivity of
budded virus, DNA synthesis, late gene expression and morphogenesis was observed
between gp16-knockout and repair viruses, but gp16 deletion resulted in six hours
of lengthening in ST50 to the third instar Spodoptera exigua larvae in bioassays.
GP16 was fractionated mainly in the light membrane fraction, by subcellular
fractionation. A GP16-EGFP fusion protein was predominantly localized close
around the nuclear membrane in infected cells, being coincident with formation of
the vesicles associated with the nuclear membrane, which hosted nucleocapsids
released from the nucleus. These data suggest that gp16 is not required for viral
replication, but may be involved in membrane trafficking associated with the
envelopment/de-envelopment of budded viruses when they cross over the nuclear
membrane and pass through cytoplasm.
PMID- 25113903
TI - 3,4-methylenedioxymethamphetamine (MDMA--Ecstasy) decreases neutrophil activity
through the glucocorticoid pathway and impairs host resistance to Listeria
monocytogenes infection in mice.
AB - Ecstasy is the popular name of the abuse drug 3,4-methylenedioxymethamphetamine
(MDMA) that decreases immunity in animals. The mechanisms that generate such
alterations are still controversial. Seven independent pharmacological approaches
were performed in mice to identify the possible mechanisms underlying the
decrease of neutrophil activity induced by MDMA and the possible effects of MDMA
on host resistance to Listeria monocytogenes. Our data showed that MDMA (10 mg
kg(-1)) administration decreases NFkappaB expression in circulating neutrophils.
Metyrapone or RU-486 administration prior to MDMA treatment abrogated MDMA
effects on neutrophil activity and NFkappaB expression, while 6-OHDA or ICI
118,551 administration did not. As MDMA treatment increased the plasmatic levels
of adrenaline and noradrenaline, propranolol pre-treatment effects were also
evaluated. Propranolol suppressed both MDMA-induced increase in corticosterone
serum levels and its effects on neutrophil activity. In a L. monocytogenes
experimental infection context, we showed that MDMA: induced myelosuppression by
decreasing granulocyte-macrophage hematopoietic progenitors (CFU-GM) in the bone
marrow but increased CFU-GM in the spleen; decreased circulating leukocytes and
bone marrow cellularity and increased spleen cellularity; decreased pro
inflammatory cytokine (IL-12p70, TNF, IFN-gamma, IL-6) and chemokine (MCP-1)
production 24 h after the infection; increased the production of pro-inflammatory
cytokines and chemokines 72 h after infection and decreased IL-10 levels at all
time points analyzed. It was proposed that MDMA immunosuppressive effects on
neutrophil activity and host resistance to L monocytogenes rely on NFkappaB
signaling, being mediated by HPA axis activity and corticosterone.
PMID- 25113906
TI - The identification and characterization of nucleic acid chaperone activity of
human enterovirus 71 nonstructural protein 3AB.
AB - Human enterovirus 71 (EV71) belongs to the genus Enterovirus in the family
Picornaviridae and has been recognized as one of the most important pathogens
that cause emerging infectious disease. Despite of the importance of EV71, the
nonstructural protein 3AB from this virus is little understood for its function
during EV71 replication. Here we expressed EV71 3AB protein as recombinant
protein in a eukaryotic expression system and uncovered that this protein
possesses a nucleic acid helix-destabilizing and strand annealing acceleration
activity in a dose-dependent manner, indicating that EV71 3AB is a nucleic acid
chaperone protein. Moreover, we characterized the RNA chaperone activity of EV71
3AB, and revealed that divalent metal ions, such as Mg(2+) and Zn(2+), were able
to inhibit the RNA helix-destabilizing activity of 3AB to different extents.
Moreover, we determined that 3B plus the last 7 amino acids at the C-terminal of
3A (termed 3B+7) possess the RNA chaperone activity, and five amino acids, i.e.
Lys-80, Phe-82, Phe-85, Tyr-89, and Arg-103, are critical and probably the active
sites of 3AB for its RNA chaperone activity. This report reveals that EV71 3AB
displays an RNA chaperone activity, adds a new member to the growing list of
virus-encoded RNA chaperones, and provides novel knowledge about the virology of
EV71.
PMID- 25113907
TI - Infectious cDNA clones of the crinivirus Tomato chlorosis virus are competent for
systemic plant infection and whitefly-transmission.
AB - Tomato chlorosis virus (ToCV) (genus Crinivirus, family Closteroviridae) causes
important emergent diseases in tomato and other solanaceous crops. ToCV is not
transmitted mechanically and is naturally transmitted by whiteflies. The ToCV
genome consists of two molecules of linear, positive-sense RNA encapsidated into
long flexuous virions. We present the construction of full-length cDNA clones of
the ToCV genome (RNA1 and RNA2) fused to the SP6 RNA polymerase promoter and
under the control of the CaMV 35S promoter. RNA1 replicated in the absence of
RNA2 in Nicotiana benthamiana and tomato protoplasts after inoculation with cDNA
derived in vitro transcripts. Agroinfiltration of RNA1 and RNA2 under the 35S
promoter resulted in systemic infection in N. benthamiana plants. In addition,
tomato plants were infected by grafting with agroinfected N. benthamiana scions,
showing the typical ToCV symptoms. The viral progeny generated in tomato was
transmissible by the whitefly Bemisia tabaci.
PMID- 25113909
TI - Palmitoylation of the Alphacoronavirus TGEV spike protein S is essential for
incorporation into virus-like particles but dispensable for S-M interaction.
AB - The spike protein S of coronaviruses contains a highly conserved cytoplasmic
cysteine-rich motif adjacent to the transmembrane region. This motif is
palmitoylated in the Betacoronaviruses MHV and SARS-CoV. Here, we demonstrate by
metabolic labeling with [(3)H]-palmitic acid that the S protein of transmissible
gastroenteritis coronavirus (TGEV), an Alphacoronavirus, is palmitoylated as
well. This is relevant for TGEV replication as virus growth was compromised by
the general palmitoylation inhibitor 2-bromopalmitate. Mutation of individual
cysteine clusters in the cysteine-rich motif of S revealed that all cysteines
must be replaced to abolish acylation and incorporation of S into virus-like
particles (VLP). Conversely, the interaction of S with the M protein, essential
for VLP incorporation of S, was not impaired by lack of palmitoylation. Thus,
palmitoylation of the S protein of Alphacoronaviruses is dispensable for S-M
interaction, but required for the generation of progeny virions.
PMID- 25113908
TI - HIV-1 Vpu mediated downregulation of CD155 requires alanine residues 10, 14 and
18 of the transmembrane domain.
AB - HIV-1 NL4-3 Vpu induces downregulation of cell surface CD155, a ligand for the
DNAM-1 activating receptor of NK and CD8(+) T cells, to evade NK cell mediated
immune response. Here we show that the conserved alanine residues at positions
10, 14 and 18 in the TM domain of Vpu are required for the efficient
downregulation of cell surface CD155. In contrast, the CK-2 phosphorylation sites
and the second alpha-helix in the cytoplasmic Vpu domain have no influence on the
surface expression of CD155. Thus, compared to Vpu's effect on CD4, NTB-A and
tetherin, the Vpu mediated downregulation of CD155 is an independent Vpu
function. We finally show that in contrast to other lentiviral strains, only Vpu
and Nef from HIV-1 M NL4-3 potently interfere with CD155 surface expression.
Thus, Vpu seems to subvert NK cell responses against HIV-1 infected T cells by
modulation of receptors necessary for NK cell activation.
PMID- 25113910
TI - 8-Hydroxy-2'-deoxyguanosine as a biomarker of oxidative DNA damage induced by
perfluorinated compounds in TK6 cells.
AB - 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is the most common biomarker of oxidative
DNA damage, it is formed by chemical carcinogens and can be measured in any
species. Perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) are
suspected genotoxic carcinogens through induction of reactive oxygen species that
are responsible for oxidative DNA damage. This study was conducted to investigate
the in vitro genotoxicity of PFOA and PFNA in human lymphoblastoid (TK6) cell
line. TK6 cells were exposed to PFOA at 0, 125, 250, and 500 ppm and PFNA at 125
and 250 ppm for 2 h. Single cell gel electrophoresis (comet assay) was used to
measure DNA damage; at least 50 cells per sample were analyzed using comet Assay
Software Project (CASP). 8-OHdG was measured in DNA of exposed cells using high
performance liquid chromatography (HPLC)-mass spectrometry (MS)/MS. Results
showed that both PFOA and PFNA induced DNA damage indicated by increased tail
length (DNA migration). The level of 8-OHdG was increased in a dose-dependent
manner in both PFOA and PFNA exposure. We concluded that PFOA and PFNA induced
DNA damage and the biomarker of oxidative DNA damage (8-OHdG) could be measured
by HPLC-MS/MS. In addition, PFNA produced high level of 8-OHdG at concentrations
lower than PFOA, this may indicate that PFNA is more potent genotoxicant for TK6
cells than PFOA.
PMID- 25113911
TI - Simultaneous T1 and T2 quantification of the myocardium using cardiac balanced
SSFP inversion recovery with interleaved sampling acquisition (CABIRIA).
AB - PURPOSE: To develop a novel sequence for simultaneous quantification of T1 and T2
relaxation times in the myocardium based on the transient phase of the balanced
steady-state free precession. METHODS: A new prototype sequence, named "cardiac
balanced-SSFP inversion recovery with interleaved sampling acquisition" (CABIRIA)
was developed based on a single-shot bSSFP readout following an inversion pulse.
With this method, T1 and T2 values can be calculated from the analysis of signal
evolution. The scan duration for a single slice in vivo was 8 heartbeats, thus
feasible in a breath-hold. The sequence was validated both in vitro by comparing
it to conventional inversion recovery and multi-echo spin-echo methods and in 5
healthy volunteers by comparing it to the Modified Look-Locker Inversion Recovery
(MOLLI) sequence and to a T2 quantification sequence based on multi-T2 -prepared
bSSFP. RESULTS: The method showed good agreement with conventional methods for
both T1 and T2 measurements (concordance correlation coefficient >= 0.99) in
vitro. In healthy volunteers the measured T1 values were 1227 +/- 68 ms and T2
values 37.9 +/- 2.4 ms, with similar inter- and intrasubject variability with
respect to existing methods. CONCLUSION: The proposed CABIRIA method enables
simultaneous quantification of myocardial T1 and T2 values with good accuracy and
precision.
PMID- 25113913
TI - A simple and precise diagnostic method for spinal muscular atrophy using a
quantitative SNP analysis system.
AB - A simple and precise diagnostic method for spinal muscular atrophy (SMA) using
high-resolution CE-based single-strand conformation polymorphism (CE-SSCP) was
developed in this study. SMA is a common genetic disorder caused by an
abnormality in the relative copy numbers of SMN1 and its centromeric copy SMN2,
which differ only in two nucleotides, namely at exons 7 and 8. Therefore, the
precise discrimination of the differences in sequence as well as their relative
quantities is crucial for the diagnosis of SMA. Multiplex ligation-dependent
probe amplification and sequence-sensitive DNA separation using hydroxyethyl
cellulose and hydroxypropyl cellulose blended polymer matrix are currently the
available methods used in the diagnosis of SMA. However, these methods are
limited by their extended hybridization step and low resolution. In this study,
the simultaneous discrimination of SMN exons 7 and 8 was successfully
demonstrated using high-resolution CE-SSCP. Unlike the previously reported
alternative method, single base differing amplicons were baseline-separated
because of its extraordinary resolution, thus providing accurate and precise
quantification of each paralog.
PMID- 25113912
TI - Cooperative signaling between homodimers of metabotropic glutamate receptors 1
and 5.
AB - Metabotropic glutamate receptors (mGluRs) function as dimers. Recent work
suggests that mGluR1 and mGluR5 may physically interact, but the nature and
functional consequences of this relationship have not been addressed. In this
study, the functional and pharmacological consequences of this interaction were
investigated. Using heterologous expression of mGluR cDNA in rat sympathetic
neurons from the superior cervical ganglion and inhibition of the native calcium
currents as an assay for receptor activation, a functional interdependence
between mGluR1 and mGluR5 was demonstrated. In neurons coexpressing these
receptors, combining a selective mGluR1 competitive antagonist with either an
mGluR1- or mGluR5-selective negative allosteric modulator (NAM) BAY36-7620
[(3aS,6aS)-hexahydro-5-methylene-6a-(2-naphthalenylmethyl)-1H-cyclopenta[c]furan
1-one] or MPEP [2-methyl-6-(phenylethynyl)pyridine hydrochloride], respectively,
strongly occluded signaling by both receptors to an approximately equal degree.
By contrast, in cells coexpressing mGluR1 and mGluR2, combining the same mGluR1
competitive inhibitor with an mGluR1 or mGluR2 NAM yielded partial and full
inhibition of the response, respectively, as expected for independently acting
receptors. In neurons expressing mGluR1 and mGluR5, the selective NAMs each
strongly inhibited the response to glutamate, suggesting that these receptors do
not interact as heterodimers, which would not be inhibited by selective NAMs.
Finally, evidence for a similar mGluR1/mGluR5 functional dependence is shown in
medium spiny striatal neurons. Together, these data demonstrate cooperative
signaling between mGluR1 and mGluR5 in a manner inconsistent with
heterodimerization, and thus suggest an interaction between homodimers.
PMID- 25113914
TI - ODE/PDE analysis of corneal curvature.
AB - The starting point for this paper is a nonlinear, two-point boundary value
ordinary differential equation (BVODE) that defines corneal curvature according
to a static force balance. A numerical solution to the BVODE is computed by first
converting the BVODE to a parabolic partial differential equation (PDE) by adding
an initial value (t, pseudo-time) derivative to the BVODE. A numerical solution
to the PDE is then computed by the method of lines (MOL) with the calculation
proceeding to a sufficiently large value of t such that the derivative in t
reduces to essentially zero. The PDE solution at this point is also the solution
for the BVODE. This procedure is implemented in R (an open source scientific
programming system) and the programming is discussed in some detail. A series
approximation to the solution is derived from which an estimate for the rate of
convergence is obtained. This is compared to a fitted exponential model. Also,
two linear approximations are derived, one of which leads to a closed form
solution. Both provide solutions very close to that obtained from the full
nonlinear model. An estimate for the cornea radius of curvature is also derived.
The paper concludes with a discussion of the features of the solution to the
ODE/PDE system.
PMID- 25113916
TI - Infants' ability to respond to depth from the retinal size of human faces:
comparing monocular and binocular preferential-looking.
AB - To examine sensitivity to pictorial depth cues in young infants (4 and 5 months
of-age), we compared monocular and binocular preferential looking to a display on
which two faces were equidistantly presented and one was larger than the other,
depicting depth from the size of human faces. Because human faces vary little in
size, the correlation between retinal size and distance can provide depth
information. As a result, adults perceive a larger face as closer than a smaller
one. Although binocular information for depth provided information that the faces
in our display were equidistant, under monocular viewing, no such information was
provided. Rather, the size of the faces indicated that one was closer than the
other. Infants are known to look longer at apparently closer objects. Therefore,
we hypothesized that infants would look longer at a larger face in the monocular
than in the binocular condition if they perceived depth from the size of human
faces. Because the displays were identical in the two conditions, any difference
in looking-behavior between monocular and binocular viewing indicated sensitivity
to depth information. Results showed that 5-month-old infants preferred the
larger, apparently closer, face in the monocular condition compared to the
binocular condition when static displays were presented. In addition, when
presented with a dynamic display, 4-month-old infants showed a stronger 'closer'
preference in the monocular condition compared to the binocular condition. This
was not the case when the faces were inverted. These results suggest that even 4
month-old infants respond to depth information from a depth cue that may require
learning, the size of faces.
PMID- 25113915
TI - Chronic Delta9-tetrahydrocannabinol administration may not attenuate simian
immunodeficiency virus disease progression in female rhesus macaques.
AB - Persons living with HIV/AIDS (PLWHA) frequently use cannabinoids, either
recreationally by smoking marijuana or therapeutically (delta-9
tetrahydrocannabinol; Delta(9)-THC dronabinol). Previously, we demonstrated that
chronic Delta(9)-THC administration decreases early mortality in male simian
immunodeficiency virus (SIV)-infected macaques. In this study, we sought to
examine whether similar protective effects resulted from chronic cannabinoid
administration in SIV-infected female rhesus macaques. Clinical and viral
parameters were evaluated in eight female rhesus macaques that received either
Delta(9)-THC (0.18-0.32 mg/kg, intramuscularly, twice daily) or vehicle (VEH)
starting 28 days prior to intravenous inoculation with SIVmac251. SIV disease
progression was assessed by changes in body weight, mortality, viral levels in
plasma and mucosal sites, and lymphocyte subsets. In contrast to our results in
male animals, chronic Delta(9)-THC did not protect SIV-infected female rhesus
macaques from early mortality. Markers of SIV disease, including viral load and
CD4(+)/CD8(+) ratio, were not altered by Delta(9)-THC compared to control
females; however, females that received chronic Delta(9)-THC did not gain as much
weight as control animals. In addition, Delta(9)-THC administration increased
total CXCR4 expression in both peripheral and duodenal CD4(+) and CD8(+) T
lymphocytes prior to SIV inoculation. Although protection from early mortality
was not evident, chronic Delta(9)-THC did not affect clinical markers of SIV
disease progression. The contrasting effects of chronic Delta(9)-THC in males
versus females remain to be explained, but highlight the need for further studies
to explore the sex-dependent effects of Delta(9)-THC and other cannabinoids on
the HIV disease course and their implications for virus transmission.
PMID- 25113918
TI - Thrombotic thrombocytopenic purpura presenting with pathologic fracture: a case
report.
AB - Thrombotic thrombocytopenic purpura is an acute syndrome with abnormalities in
multiple organ systems, which becomes manifest with microangiopathic hemolytic
anemia and thrombocytopenia. The hereditary or acquired deficiency of ADAMTS-13
activity leads to an excess of high molecular weight von Willebrand factor
multimers in plasma, leading to platelet aggregation and diffuse intravascular
thrombus formation, resulting in thrombotic thrombocytopenic purpura. Thrombotic
lesions occurring in TTP leads to ischemia and convulsion. Depending on the
properties of the bony tissue, fractures are divided into three groups as
traumatic, pathological, and stress fractures. A pathologic fracture is a broken
bone caused by disease leading to weakness of the bone. This process is most
commonly due to osteoporosis, but may also be due to other pathologies such as
cancer, infections, inherited bone disorders, or a bone cyst. We herein report a
case with a pathologic fracture due to convulsion secondary to thrombotic
thrombocytopenic pupura. Thrombotic lesions occurring in TTP may lead to ischemia
and convulsion, as in our patient and pathological fractures presented in our
case report may occur as a result of severe muscle contractions associated with
convulsive activity. Thrombotic thrombocytopenic pupura is a disease that
involves many organ systems and thus may have a very wide spectrum of clinical
presentations.
PMID- 25113917
TI - Maternal prenatal stress and infant regulatory capacity in Mexican Americans.
AB - The early postpartum period lays important groundwork for later self-regulation
as infants' dispositional traits interact with caregivers' co-regulatory
behaviors to produce the earliest forms of self-regulation. Although emerging
literature suggests that fetal exposure to maternal stress may be integral in
determining child self-regulatory capacity, the complex pathways that
characterize these early developmental processes remain unclear. The current
study considers these complex, transactional processes in a low income, Mexican
American sample. Data were collected from 295 Mexican American infants and their
mothers during prenatal, 6- and 12-week postpartum home interviews. Mother
reports of stress were obtained prenatally, and mother reports of infant
temperament were obtained at 6 weeks. Observer ratings of maternal sensitivity
and infant regulatory behaviors were obtained at the 6- and 12-week time points.
Study results indicate that prenatal stress predicts higher levels of infant
negativity and surgency, both of which directly or interactively predict later
engagement in regulatory behaviors. Unexpectedly, prenatal stress also predicted
more engagement in orienting, but not self-comforting behaviors. Advancing
understandings about the nature of these developmental pathways may have
significant implications for targets of early intervention in this high risk
population.
PMID- 25113919
TI - Response to Dr. Rice M and colleagues on their letter to editor regarding
"validation of a non-invasive pulse CO-oximetry based hemoglobin estimation in
normal blood donors," Transfusion and Apheresis Science 2013 Nov 4. Accurate
enough for the spectrum tested.
PMID- 25113920
TI - [Transferable skills of healthcare professionals in providing homecare in
chronically ill patients].
AB - AIM: To determine the relevance level of non-technical skills of those
professionals dedicated to the healthcare of patients with chronic diseases, from
an analysis of home care professionals. DESIGN: Quantitative and qualitative
research conducted in 2 phases: 1.st from November 2010 to March 2011 and 2.nd
from December 2012 to August 2013. SETTING: Health Region of Barcelona city.
PARTICIPANTS: During the 1.st phase, 30 professionals from homecare teams (3 from
Primary Care and 3 from Hospitals). In 2.nd phase, 218 professionals from 50
Primary Healthcare Centres and 7 home care programmes. METHOD: Purposive sampling
in was used in the1st phase, and randomized sampling in the 2.nd phase. Likert
scales and focus group were used. RESULTS: A total of 19 skill categories were
identified in the 1.st phase. In the 2.nd phase 3 metacategories were
established: comprehensive patient-centered care, interprofessional organization,
and inter-health care fields and interpersonal skills. CONCLUSIONS: It is
necessary to improve and secure the professionals relationships between levels of
healthcare, continuity of healthcare, biopsychosocial model and holistic
attention to patients and relatives, looking at emotions, expectations, feelings,
beliefs and values. It is essential to design and implement continuing training
in transferable skills in every healthcare centre, through active methodologies.
PMID- 25113921
TI - [Inappropriate prescribing in polymedicated patients over 64 years-old in primary
care].
AB - OBJECTIVE: To describe inappropriate prescribing (IP) in the polymedicated
population over 64 years-old in primary care using the STOPP/START criteria.
DESIGN: The study design was descriptive, cross-sectional and multicenter.
LOCATION: Four urban primary care centers in Barcelona. Participants Patients
over 64 years-old with more than 5 prescribed drugs for at least 6 months
(n=467). Main measurements Major health problems, chronically prescribed drugs,
and percentage of IP using the STOPP/START criteria were studied. Percentage of
IP considered as the percentage of patients with at least one STOPP or START non
compliance criterion was calculated with a 95%CI. Chi-square was used for
statistical analysis. RESULTS: The mean age was 77.3 (+/- 7.0 SD) with a mean of
8.9 (+/- 2.8 SD) prescribed drugs. IP was higher the greater the number of drugs
prescribed (p<0,01). 326 patients (76.4% [95%CI: 72.2 to 80.6]) had at least one
IP, according to STOPP/START criteria. STOPP IP affected 51.4% of the patients
and START IP 53.6%. The most frequent causes of IP were antiplatelet agents, for
both over-prescribing (10.2%) and omission (17.9%). Prolonged use of
benzodiazepines (6.6%) and duplications (6.4%) followed in prevalence.
CONCLUSIONS: IP in polymedicated patients in primary care was very high. IP was
similar for drugs that should be withdrawn or started. The most common causes of
IP were antiplatelet agents, benzodiazepines and drug duplication.
PMID- 25113922
TI - [The adaptation and validation to Spanish of the questionnaire Aid to Capacity
Evaluation (ACE), for the assessment of the ability of patients in medical
decision-making].
AB - OBJECTIVE: To adapt and validate the Spanish version of the Aid to Capacity
Evaluation scale, designed to assess the capacity of the adult in medical
decision-making, both in diagnosis and treatment processes. DESIGN: Observational
study of prospective validation. SETTING: Primary and hospital care of the basic
health area of Jaen. PARTICIPANTS: One hundred twenty-nine patients. MAIN
MEASUREMENTS: Questionnaire which included sociodemographic variables, concerning
the decision (scope, type of decision, the need for written informed consent),
assessment of the capacity to the Aid to Capacity Evaluation scale and other
related comorbidity (hearing loss, alcoholism, cognitive level variables with the
Mini-Mental State Examination and depression by Goldberg or Yesavage test).
RESULTS: The tool is considered viable. The conclusions of the expert panel were
favorable. The result of the criteria' validity, comparing the results with the
assessment of the experts (forensic and psychiatrist) was very satisfying
(P<.001). The intra-observer reliability was low (kappa=0,135). Interobserver
reliability remained high (kappa=0.74). The internal consistency was awarded an
alpha of Cronbach's 0,645 for the reduced model of 6 items. CONCLUSIONS: The Aid
to Capacity Evaluation scale was adapted to Spanish, demonstrating adequate
internal consistency and construct validity. Its use in clinical practice could
contribute to the identification of patients unable to make a particular medical
decision and/or to give an informed consent.
PMID- 25113923
TI - Can the therapeutic relationship predict 18 month outcomes for individuals with
psychosis?
AB - Therapeutic relationships (TRs) are considered a key component of good
psychiatric care, yet its association with outcomes for individuals with
psychosis remains unclear. Five hundred and sixty-nine service users with
psychotic disorders and care coordinators in community settings rated their
therapeutic relationship; outcomes were assessed 18 months later. In multivariate
analyses, a small but significant association was found between service user
ratings and instances of psychiatric hospital admissions, self harm and suicide
attempts over an 18 month period. Care coordinator ratings were associated with
instances of psychiatric hospital admissions and harm to others over the 18
months and level of functioning at 18 months. The differential findings and small
effect size suggests that the therapeutic relationship needs further definition
for this patient group in this setting. Nevertheless, clinicians should
prioritise interactions that strengthen therapeutic relationships.
PMID- 25113924
TI - Prevalence of schizophrenia disability and associated mortality among Chinese men
and women.
AB - Schizophrenia is a major cause of psychiatric disability in China. In the present
study, we estimated total and age-specific prevalence of both schizophrenia
disability and associated mortality among Chinese women and men. We further
examined whether sex differences in prevalence were attributable to mortality
differences between men and women. Data from the Second China National Sample
Survey on Disability (2006) and the 2007-2010 follow-up studies were utilized.
Possibly psychiatrically disabled individuals were administered the World Health
Organization Disability Assessment Schedule, Version II and the ICD-10 Symptom
Checklist for Mental Disorders by trained clinical psychiatrists. In total, 0.37%
of men and 0.44% of women were living with schizophrenia disability in China. We
did not find statistically significant differences in the 4-year cumulative
mortality between men and women. Overall standardized mortality ratios for the
age groups of 18-29, 30-39, 40-49, 50-59, 60-69, and 70+ years were 120.89,
29.56, 15.06, 9.16, 10.57, and 4.95, respectively. In conclusion, mortality
differences between men and women were unlikely to be a major contributor to sex
differences in prevalence. Premature death among younger individuals experiencing
schizophrenia disability warrants urgent attention.
PMID- 25113925
TI - Sweet taste sensitivity is influenced by 5-HTTLPR genotype and affected in
seasonal affective disorder.
PMID- 25113926
TI - Biogenetic explanations and emotional reactions to people with schizophrenia and
major depressive disorder.
AB - Using population-based data, the relationship between biogenetic causal beliefs
and emotional reactions to persons with schizophrenia or depression was examined.
Biogenetic attributions elicited either negative emotions alone or pro-social and
negative emotions at the same time. Biogenetic attributions seem not helpful for
improving emotional reactions to people with mental disorders.
PMID- 25113927
TI - Phosphathiahelicenes: synthesis and uses in enantioselective gold catalysis.
AB - Enantiomerically pure thiahelicenes displaying a terminal phosphole unit and a
stereogenic phosphorus center have been prepared by oxidative photocyclization of
a diaryl-olefin precursor. Starting from one of these phosphathiahelicene oxides,
the corresponding trivalent phosphine-Au(I) complex is obtained with complete
diastereoselectivity. It affords a new, excellent precatalyst for the
enantioselective cycloisomerization of N-tethered enynes (up to 96 % ee).
PMID- 25113928
TI - High accuracy NMR chemical shift corrected for bulk magnetization as a tool for
structural elucidation of dilutable microemulsions. Part 1 - Proof of concept.
AB - In microemulsions, changes in droplet size and shape and possible transformations
occur under various conditions. They are difficult to characterize by most
analytical tools because of their nano-sized structure and dynamic nature.
Several methods are usually combined to obtain reliable information, guiding the
scientist in understanding their physical behavior. We felt that there is a need
for a technique that complements those in use today in order to provide more
information on the microemulsion behavior, mainly as a function of dilution with
water. The improvement of NMR chemical shift measurements independent of bulk
magnetization effects makes it possible to study the very weak intermolecular
chemical shift effects. In the present study, we used NMR high resolution magic
angle spinning to measure the chemical shift very accurately, free of bulk
magnetization effects. The chemical shift of microemulsion components is measured
as a function of the water content in order to validate the method in an
interesting and promising, U-type dilutable microemulsion, which had been
previously studied by a variety of techniques. Phase transition points of the
microemulsion (O/W, bicontinuous, W/O) and changes in droplet shape were
successfully detected using high-accuracy chemical shift measurements. We
analyzed the results and found them to be compatible with the previous studies,
paving the way for high-accuracy chemical shifts to be used for the study of
other microemulsion systems. We detected two transition points along the water
dilution line of the concentrate (reverse micelles) corresponding to the
transition from swollen W/O nano-droplets to bicontinuous to the O/W droplets
along with the changes in the droplets' sizes and shapes. The method seems to be
in excellent agreement with other previously studied techniques and shows the
advantage of this easy and valid technique.
PMID- 25113929
TI - Radium isotopes ((226)Ra and (228)Ra) in Na-Cl type groundwaters from Tohoku
District (Aomori, Akita and Yamagata Prefectures) in Japan.
AB - A total of 28 Na-Cl type groundwater samples were collected from Aomori, Akita
and Yamagata Prefectures, in the Tohoku District of Japan, and their radium
isotope ((226)Ra and (228)Ra) concentrations were measured along with their
chemical components and stable isotope ratios (delta(2)H and delta(18)Os). The
(226)Ra concentrations in groundwater samples varied widely, ranging from 8.8 to
1587 mBq kg(-1). These concentrations showed an increasing tendency with the
increase of the total dissolved solid (TDS) contents. The (228)Ra/(226)Ra
activity ratios were in the range from 0.3 to 4.2, with most data being around
0.5-2. These ratios were within those of (232)Th/(238)U found in granitic and
related rocks and so on in Japan, indicating that Ra isotopes mainly ejected into
the groundwater by the alpha-recoil process. The relationship between (226)Ra and
other parameters suggested that Ra isotopes in groundwater samples in this study
were mainly constrained by adsorption-desorption reactions depending on salinity
with wide variation. Clear correlation between (226)Ra-Ca, (226)Ra-Sr, (226)Ra-Ba
and (226)Ra-TDS observed in sulfate-free groundwater samples indicated that Ra
isotopes of them were constrained by adsorption-desorption reactions depending on
salinity under reducing condition. In contrast, relationship of (226)Ra-Ca,
(226)Ra-Sr, (226)Ra-Ba and (226)Ra-TDS in sulfate-containing groundwater samples
varied widely, and then, removal or enhanced mobility of Ra isotopes of them were
observed.
PMID- 25113931
TI - In search of next generation antimalarials.
AB - Compounds 7-10 displayed potency without any apparent toxicity, in animal models
of both relapsing and non-relapsing forms of malaria offering hope of a single
molecule that can cure both relapsing and non relapsing forms of malaria.
PMID- 25113930
TI - Kinase domain inhibition of leucine rich repeat kinase 2 (LRRK2) using a
[1,2,4]triazolo[4,3-b]pyridazine scaffold.
AB - Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson's
disease (PD). The most common mutant, G2019S, increases kinase activity, thus
LRRK2 kinase inhibitors are potentially useful in the treatment of PD. We herein
disclose the structure, potential ligand-protein binding interactions, and
pharmacological profiling of potent and highly selective kinase inhibitors based
on a triazolopyridazine chemical scaffold.
PMID- 25113932
TI - Optimization of 2-phenyl-pyrimidine-4-carboxamides towards potent, orally
bioavailable and selective P2Y(12) antagonists for inhibition of platelet
aggregation.
AB - 2-Phenyl-pyrimidine-4-carboxamide analogs were identified as P2Y12 antagonists.
Optimization of the carbon-linked or nitrogen-linked substituent at the 6
position of the pyrimidine ring provided compounds with excellent ex vivo potency
in the platelet aggregation assay in human plasma. Compound 23u met the
objectives for activity, selectivity and ADMET properties.
PMID- 25113934
TI - Discovery of pyrrolo-benzo-1,4-diazines as potent Na(v)1.7 sodium channel
blockers.
AB - A series of pyrrolo-benzo-1,4-diazine analogs have been synthesized and displayed
potent Nav1.7 inhibitory activity and moderate selectivity over Nav1.5. The
syntheses, structure-activity relationships, and selected pharmacokinetic data of
these analogs are described. Compound 41 displayed anti-nociceptive efficacy in
the rat CFA pain model at 100 mpk oral dosing.
PMID- 25113933
TI - Oleanolic acid analogs as NO, TNF-alpha and IL-1beta inhibitors: synthesis,
biological evaluation and docking studies.
AB - A series of oleanolic acid analogs, characterized by structural modifications at
position C-3 and C-28 of oleanane skeleton were synthesized and assessed for
antiinflammatory potential towards lipopolysaccharide (LPS) induced nitric oxide
(NO) production in macrophages. Results revealed that all the synthesized analogs
of oleanolic acid inhibit NO production with an IC50 of 2.66-41.7 MUM as compared
to the specific nitric oxide synthase (NOS) inhibitor, L-NAME (IC50=69.21 and
73.18 MUM on RAW 264.7 and J774A.1 cells, respectively) without affecting the
cell viability when tested at their half maximal concentration. The most potent
NO inhibitors (2, 8, 9 and 10) at a concentration of 20 MUg/mL also demonstrated
mild inhibition (27.9-51.9%) of LPS-induced tumor necrosis factor alpha (TNF
alpha) and weak inhibition (11.1-37.5%) towards interleukin 1-beta (IL-1beta)
production in both the cells. The present study paves a direction that analogs of
oleanolic acid can be employed as a lead in the development of potent NO
inhibitors. Molecular docking studies also showed that 10 (with top Goldscore
docking pose 19.05) showed similar interaction as that of co-crystallized
inhibitor and, thereby, helps to design the potent inhibitors of TNF-alpha.
PMID- 25113935
TI - Cellular differentiation assessments by measuring the degree of cellular
internalization and membrane adsorption using designed peptides.
AB - We demonstrate examples of cellular differentiation assessments, including
cellular neurite outgrowth and fat cell maturation, by measuring the degree of
membrane adsorption or cellular internalization using designed peptides. Because
changes in the cellular membrane and cytosol during differentiation were shown to
influence membrane adsorption and cellular internalization, we could successfully
evaluate the extent of differentiation simply like stain indicators.
PMID- 25113936
TI - Online dietary intake estimation: reproducibility and validity of the Food4Me
food frequency questionnaire against a 4-day weighed food record.
AB - BACKGROUND: Advances in nutritional assessment are continuing to embrace
developments in computer technology. The online Food4Me food frequency
questionnaire (FFQ) was created as an electronic system for the collection of
nutrient intake data. To ensure its accuracy in assessing both nutrient and food
group intake, further validation against data obtained using a reliable, but
independent, instrument and assessment of its reproducibility are required.
OBJECTIVE: The aim was to assess the reproducibility and validity of the Food4Me
FFQ against a 4-day weighed food record (WFR). METHODS: Reproducibility of the
Food4Me FFQ was assessed using test-retest methodology by asking participants to
complete the FFQ on 2 occasions 4 weeks apart. To assess the validity of the
Food4Me FFQ against the 4-day WFR, half the participants were also asked to
complete a 4-day WFR 1 week after the first administration of the Food4Me FFQ.
Level of agreement between nutrient and food group intakes estimated by the
repeated Food4Me FFQ and the Food4Me FFQ and 4-day WFR were evaluated using Bland
Altman methodology and classification into quartiles of daily intake. Crude
unadjusted correlation coefficients were also calculated for nutrient and food
group intakes. RESULTS: In total, 100 people participated in the assessment of
reproducibility (mean age 32, SD 12 years), and 49 of these (mean age 27, SD 8
years) also took part in the assessment of validity. Crude unadjusted
correlations for repeated Food4Me FFQ ranged from .65 (vitamin D) to .90
(alcohol). The mean cross-classification into "exact agreement plus adjacent" was
92% for both nutrient and food group intakes, and Bland-Altman plots showed good
agreement for energy-adjusted macronutrient intakes. Agreement between the
Food4Me FFQ and 4-day WFR varied, with crude unadjusted correlations ranging from
.23 (vitamin D) to .65 (protein, % total energy) for nutrient intakes and .11
(soups, sauces and miscellaneous foods) to .73 (yogurts) for food group intake.
The mean cross-classification into "exact agreement plus adjacent" was 80% and
78% for nutrient and food group intake, respectively. There were no significant
differences between energy intakes estimated using the Food4Me FFQ and 4-day WFR,
and Bland-Altman plots showed good agreement for both energy and energy
controlled nutrient intakes. CONCLUSIONS: The results demonstrate that the online
Food4Me FFQ is reproducible for assessing nutrient and food group intake and has
moderate agreement with the 4-day WFR for assessing energy and energy-adjusted
nutrient intakes. The Food4Me FFQ is a suitable online tool for assessing dietary
intake in healthy adults.
PMID- 25113939
TI - Estimated life expectancy and risk of death from cancer by quartiles in the older
Japanese population: 2010 vital statistics.
AB - Data on life expectancies and risk of death from cancer are essential information
to have when making informed decisions about cancer screening and treatment
options, but has never been presented in a way that is readily available to use
for physicians in Japan. We provided estimates of life expectancies and predicted
risk of death from seven most common types of cancer (lung, gastric, liver,
colon, prostate, breast, and cervical) by quartiles for the older Japanese
population above 50 years old, using 2010 life tables and cancer mortality
statistics data. We found that there was a large difference in life expectancy
between older persons in the upper and lower quartiles. Risk of death from breast
cancer was low. By using this data, physicians can more accurately obtain life
expectancy estimates by assessing which quartile the patient is most likely to
fall under, and help patients make better informed decisions.
PMID- 25113940
TI - Epidemiology of childhood leukemia in the presence and absence of Down syndrome.
AB - Down syndrome (DS) is a common congenital anomaly, and children with DS have a
substantially higher risk of leukemia. Although understanding of genetic and
epigenetic changes of childhood leukemia has improved, the causes of childhood
leukemia and the potential role of environmental exposures in leukemogenesis
remain largely unknown. Although many epidemiologic studies have examined a
variety of environmental exposures, ionizing radiation remains the only generally
accepted environmental risk factor for childhood leukemia. Among suspected risk
factors, infections, exposure to pesticides, and extremely low frequency magnetic
fields are notable. While there are well-defined differences between leukemia in
children with and without DS, studies of risk factors for leukemia among DS
children are generally consistent with trends seen among non-DS (NDS) children.
We provide background on DS epidemiology and review the similarities and
differences in biological and epidemiologic features of leukemia in children with
and without DS. We propose that both acute lymphoblastic and acute myeloblastic
leukemia among DS children can serve as an informative model for development of
childhood leukemia. Further, the high rates of leukemia among DS children make it
possible to study this disease using a cohort approach, a powerful method that is
unfeasible in the general population due to the rarity of childhood leukemia.
PMID- 25113938
TI - Statin use and risk of hepatocellular carcinoma in a U.S. population.
AB - PURPOSE: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are
medications widely prescribed to reduce cholesterol levels. Observational studies
in high-risk populations, mostly in Asia, have suggested that statins are
associated with a reduced risk of hepatocellular carcinoma (HCC). The current
study sought to evaluate the association of statin use and HCC in a U.S.-based,
low-risk, general population. METHODS: A nested case-control study was conducted
among members of the Health Alliance Plan HMO of the Henry Ford Health System
enrolled between 1999 and 2010. Electronic pharmacy records of statin use were
compared among tumor registry-confirmed cases of HCC (n=94) and controls (n=468)
matched on age, sex, diagnosis date, and length of HMO enrolment. RESULTS: In
multivariate analyses, ever-use of statins was significantly inversely associated
with development of HCC (Odds ratio (OR): 0.32, 95%CI: 0.15-0.67). No clear dose
response relationship was evident as statin use for <2 years (OR=0.32, 95%CI=0.13
0.83) and >2 years (OR=0.31, 95CI%=0.12-9.81) resulted in very similar ORs.
CONCLUSIONS: The use of statins among populations in low-risk HCC areas may be
associated with decreased risk of HCC.
PMID- 25113942
TI - A practical tool to evaluate dose distributions using radiochromic film in
radiation oncology.
AB - PURPOSE: Triple channel algorithm and specific procedures make more reliable
radiochromic dosimetry for treatment planning verification and quality assurance
in radiation therapy. A tool to obtain radiochromic dose distributions and
compare them with the ones resulting from a treatment planning system was
developed and applied. METHODS: The tool was developed as Microsoft Excel macro;
it builds dose calibration curves against net optical density of Gafchromic EBT3
film, produces axial, coronal and sagittal dose maps and allows to evaluate them
against dose distributions calculated by the Varian treatment planning system
Eclipse using gamma index and gamma angle. RESULTS: The net optical density
standard errors of estimate of calibration curves at 6 MV Varian DBX600 linac
energy were 0.2%, 0.4% and 0.2% for the red, green and blue channels. Tests of
these curves by means of three independent eight dose points measurement series,
at 15 MV and 6 MV Varian 2100C linac and at 6 MV DBX600 linac energies, showed
less than 2% of dose errors for the red channel and less than 3% for the green
channel in the range 100-450 cGy. The comparisons between dose distributions from
Gafchromic EBT3 triple channel algorithm and the ones from Eclipse analytic
anisotropic algorithm (AAA) showed values of gamma index 95th percentile between
0.6 and 1.0. CONCLUSION: The obtained results encourage the application of this
tool in radiation therapy quality assurance.
PMID- 25113941
TI - Cell-friendly inverse opal-like hydrogels for a spatially separated co-culture
system.
AB - Three-dimensional macroporous scaffolds have extensively been studied for cell
based tissue engineering but their use is mostly limited to mechanical support
for cell adhesion and growth on the surface of macropores. Here, a templated
fabrication method is described to prepare cell-friendly inverse opal-like
hydrogels (IOHs) allowing both cell encapsulation within the hydrogel matrix and
cell seeding on the surface of macropores. Ionically crosslinked alginate
microbeads and photocrosslinkable biocompatible polymers are used as a
sacrificial template and as a matrix, respectively. The alginate microbeads are
easily removed by a chelating agent, with minimal toxicity for the encapsulated
cells during template removal. The outer surface of macropores in IOHs can also
provide a space for cell adherence. The cells encapsulated or attached in IOHs
are able to remain viable and to proliferate over time. The elastic modulus and
cell-adhesion properties of IOHs can be easily controlled and tuned. Finally, it
is demonstrated that IOH can be used to co-culture two distinct cell populations
in different spatial positions. This cell-friendly IOH system provides a 3D
scaffold for organizing different cell types in a controllable microenvironment
to investigate biological processes such as stem cell niches or tumor
microenvironments.
PMID- 25113944
TI - Systemic progesterone therapy--oral, vaginal, injections and even transdermal?
AB - Several medicinal products containing progesterone are in widespread use orally
for protection of the endometrium during concurrent oestrogen treatment, and
injections or vaginally for support of luteal function during assisted
reproduction. These indications have been established in extensive clinical
testing programmes. In addition, the results of recent studies and meta-analyses
suggest that vaginal progesterone is an effective method for preventing premature
births in singleton pregnancies in women with a shortened cervix. In US, 17alpha
hydroxyprogesterone caproate is licensed to reduce the risk of preterm birth in
women with a singleton pregnancy who have a history of singleton spontaneous
preterm birth. There is insufficient evidence from scientific studies to
substantiate the transdermal application of progesterone. In particular, these
preparations should not be used to oppose the effects of oestrogen on the
endometrium, because even with low doses of estradiol a reliable progestogenic
effect to protect the endometrium has not been proved. On the other hand, the
application of transdermal progesterone preparations alone is not known to pose
any risks to health.
PMID- 25113943
TI - Static and rotational intensity modulated techniques for head-neck cancer
radiotherapy: a planning comparison.
AB - PURPOSE: To compare helical Tomotherapy (HT), two volumetric-modulated arc
techniques and conventional fixed-field intensity modulated techniques (S-IMRT)
for head-neck (HN) cancers. METHODS AND MATERIALS: Eighteen HN patients were
considered. Four treatment plans were generated for each patient: HT, S-IMRT
optimised with Eclipse treatment planning system and two volumetric techniques
using Elekta-Oncentra approach (VMAT) and Varian-RapidArc (RA), using two full
arcs. All techniques were optimised to simultaneously deliver 66Gy to PTV1 (GTV
and enlarged nodes) and 54Gy to PTV2 (subclinical and electively treated nodes).
Comparisons were assessed on several dosimetric parameters and, secondarily, on
planned MUs and delivery time. RESULTS: Concerning PTV coverage, significantly
better results were found for HT and RA. HT significantly improved the target
coverage both compared to S-IMRT and VMAT. No significant differences were found
between S-IMRT and volumetric techniques in terms of dose homogeneity. For OARs,
all the techniques were able to satisfy all hard constraints; significantly
better results were found for HT, especially in the intermediate dose range (15
30 Gy). S-IMRT reached a significantly better OARs sparing with respect to VMAT
and RA. No significant differences were found for body mean dose, excepting
higher values of V5-V10 for HT. A reduction of planned MUs and delivery treatment
time was found with volumetric techniques. CONCLUSIONS: The objectives of
satisfying target coverage and sparing of critical structures were reached with
all techniques. S-IMRT techniques were found more advantageous compared to RA and
VMAT for OARs sparing. HT reached the best overall treatment plan quality.
PMID- 25113945
TI - Recently targeted kinases and their inhibitors-the path to clinical trials.
AB - Protein kinases have emerged as one of the most important drug target families
for the treatment of cancer. To date, 28 inhibitors with reported activity versus
one or multiple kinases have been approved for clinical use. However, the
majority of new clinical trials are focused on new subindications using already
approved kinase inhibitors or target well validated kinase targets with novel
inhibitors. In contrast, relatively few clinical trials have been initiated using
specific inhibitors that inhibit novel kinase targets, despite significant
validation efforts in the public domain. Analysis of the target validation
history of first in class kinase inhibitors revealed a long delay between initial
disease association and development of inhibitors. As part of this analysis, we
have investigated which first in class inhibitor that entered phase I clinical
trials over the last five years and also considered which research approaches
that were used to validate them.
PMID- 25113946
TI - Metabolic modeling of spatial heterogeneity of biofilms in microbial fuel cells
reveals substrate limitations in electrical current generation.
AB - Microbial fuel cells (MFCs) have been proposed as an alternative energy resource
for the conversion of organic compounds to electricity. In an MFC, microorganisms
such as Geobacter sulfurreducens form an anode-associated biofilm that can
completely oxidize organic matter (electron donor) to carbon dioxide with direct
electron transfer to the anode (electron acceptor). Mathematical models are
useful in analyzing biofilm processes; however, existing models rely on Nernst
Monod type expressions, and evaluate extracellular processes separated from the
intracellular metabolism of the microorganism. Thus, models that combine both
extracellular and intracellular components, while addressing spatial
heterogeneity, are essential for improved representation of biofilm processes.
The goal of this work is to develop a model that integrates genome-scale
metabolic models with the model of biofilm environment. This integrated model
shows the variations of electrical current production and biofilm thickness under
the presence/absence of NH4 in the bulk solution, and under varying maintenance
energy demands. Further, sensitivity analysis suggested that conductivity is not
limiting electrical current generation and that increasing cell density can lead
to enhanced current generation. In addition, the modeling results also highlight
instances such as the transformation into respiring cells, where the mechanism of
electrical current generation during biofilm development is not yet clearly
understood.
PMID- 25113948
TI - Microalgal and cyanobacterial cultivation: the supply of nutrients.
AB - Microalgae and cyanobacteria are a promising new source of biomass that may
complement agricultural crops to meet the increasing global demand for food,
feed, biofuels and chemical production. Microalgae and cyanobacteria cultivation
does not interfere directly with food production, but care should be taken to
avoid indirect competition for nutrient (fertilizer) supply. Microalgae and
cyanobacteria production requires high concentrations of essential nutrients
(C,N,P,S,K,Fe, etc.). In the present paper the application of nutrients and their
uptake by microalgae and cyanobacteria is reviewed. The main focus is on the
three most significant nutrients, i.e. carbon, nitrogen and phosphorus; however
other nutrients are also reviewed. Nutrients are generally taken up in the
inorganic form, but several organic forms of them are also assimilable. Some
nutrients do not display any inhibition effect on microalgal or cyanobacterial
growth, while others, such as NO2 or NH3 have detrimental effects when present in
high concentrations. Nutrients in the gaseous form, such as CO2 and NO face a
major limitation which is related mainly to their mass transfer from the gaseous
to the liquid state. Since the cultivation of microalgae and cyanobacteria
consumes considerable quantities of nutrients, strategies to improve the nutrient
application efficiency are needed. Additionally, a promising strategy to improve
microalgal and cyanobacterial production sustainability is the utilization of
waste streams by recycling of waste nutrients. However, major constraints of
using waste streams are the reduction of the range of the biomass applications
due to production of contaminated biomass and the possible low bio-availability
of some nutrients.
PMID- 25113947
TI - Hybrid ferrihydrite-MF/UF membrane filtration for the simultaneous removal of
dissolved organic matter and phosphate.
AB - Dissolved organic matter (DOM) and phosphorus promote microbial regrowth in water
distribution networks. Ferrihydrite (Fh) has a high adsorption affinity with DOM
and phosphate. Hence, a lab-scale unit of the hybrid Fh-MF/UF membrane filtration
system was used to evaluate membrane fouling and the removal efficiency of DOM
and phosphate. Suwannee River natural organic matter (SRNOM) was used as a
surrogate for DOM in natural water. The Fh-membrane system demonstrated removal
rates of dissolved organic carbon (DOC), UV254 and phosphate up to 50%, 80% and
90%, respectively, at the Fh dose of 17.5 mg/L. The effect of phosphate on the
removal of DOM was different without or with the addition of Fh; namely,
phosphate increased the DOM removal without Fh by interacting with the UF
membrane made of regenerated cellulose (RC), but phosphate decreased the DOM
removal by Fh due to the strong affinity of phosphate with Fh. Size exclusion
chromatography revealed that phosphate mainly competed against smaller DOM
molecules for Fh adsorption sites. Although the addition of Fh caused only a
moderate flux decline with the RC membranes, the deposition of positively charged
Fh on the surface of a negatively charged high-flux membrane, i.e.,
polyethersulfone (PES), caused a rapid decline of the permeation flux.
PMID- 25113949
TI - Development of a polydimethylsiloxane-thymol/nitroprusside composite based sensor
involving thymol derivatization for ammonium monitoring in water samples.
AB - This report describes a polydimethylsiloxane (PDMS)-thymol/nitroprusside delivery
composite sensor for direct monitoring of ammonium in environmental water
samples. The sensor is based on a PDMS support that contains the Berthelot's
reaction reagents. To prepare the PDMS-thymol/nitroprusside composite discs,
thymol and nitroprusside have been encapsulated in the PDMS matrix, forming a
reagent release support which significantly simplifies the analytical
measurements, since it avoids the need to prepare derivatizing reagents and
sample handling is reduced to the sampling step. When, the PDMS
thymol/nitroprusside composite was introduced in water samples spontaneous
release of the chromophore and catalyst was produced, and the derivatization
reaction took place to form the indothymol blue. Thus, qualitative analysis of
NH4(+) could be carried out by visual inspection, but also, it can be quantified
by measuring the absorbance at 690 nm. These portable devices provided good
sensitivity (LOD<0.4 mg L(-1)) and reproducibility (RSD <10%) for the rapid
detection of ammonium. The PDMS-NH4(+) sensor has been successfully applied to
determine ammonium in water samples and in the aqueous extracts of particulate
matter PM10 samples. Moreover, the reliability of the method for qualitative
analysis has been demonstrated. Finally, the advantages of the PDMS-NH4(+) sensor
have been examined by comparing some analytical and complementary characteristics
with the properties of well-established ammonium determination methods.
PMID- 25113950
TI - Heart rate control with single administration of a long-acting beta-blocker at
bedtime before coronary computed tomography angiography.
AB - BACKGROUND: Beta-blockers are used to control the heart rate prior to coronary
computed tomography (CT) angiography. However, in-hospital administration is time
consuming, and it is hard to decrease the heart rate to <60 beats per minute
(bpm) when the initial heart rate is increased. In this study, we examined
whether the single administration of long-acting beta-blocker at bedtime before
angiography is effective for achieving the target heart rate. METHODS AND
RESULTS: A total of 314 consecutive patients with a resting heart rate >60bpm who
underwent coronary CT angiography were retrospectively collected. Either
bisoprolol or atenolol was orally administered the night before to 166 patients
(beta group), and no additional medication was administered to the other 148
patients (control group). When the heart rate was >60bpm on arrival, a beta
blocker or verapamil was orally administered at the discretion of the physician.
Although the baseline heart rate was not significantly different between the
groups, the beta-blocker treatment the night before significantly reduced the
heart rate compared to control group upon arrival at the hospital and at the time
of angiography. The rate of achievement of a heart rate <=60bpm on arrival at the
hospital was significantly higher in the beta group, and even after the
additional treatment. CONCLUSIONS: Bedtime administration of a long-acting beta
blocker the night before coronary CT angiography is an effective option to
achieve the target heart rate at the time of examination.
PMID- 25113951
TI - Management of ostium secundum atrial septal defect in the era of percutaneous
trans-catheter device closure: 7-Year experience at a single institution.
AB - OBJECTIVES: This study aimed to review the single institutional experience of the
repair of secundum atrial septal defect (ASD) after the initiation of
percutaneous trans-catheter device closure, to confirm the current management
strategy and outcomes. METHODS: From August 2005 to December 2012, a total of
1026 (659 females, age 27+/-21 years) consecutive patients underwent the repair
of ASD. Including eight patients who converted to surgical repair, 317 patients
(31%) underwent surgical repair and 709 (69%) underwent trans-catheter device
closure. RESULTS: An embolized device into the left atrium was surgically
retrieved in one patient soon after trans-catheter device closure without any
postoperative complications. The other patient developed left atrium to aorta
fistula due to late erosion, and required the removal of implanted device and
patch closure of fistula and ASD 3 months after trans-catheter device closure.
Whereas serious central nerve system complications occurred in three patients
after the surgical repair including a 75-year-old patient with postoperative
transient atrial fibrillation who subsequently developed aspiration pneumonia and
died; there were no mortalities and no morbidities associated with cranial nerve
function after trans-catheter device closure. A number of patients approached
through partial sternotomy with limited skin incision have increased per year,
and the length of skin incision was 5.1+/-1.2cm in pediatric patients weighing
less than 15kg (n=40), 6.9+/-1.9cm in the remaining pediatric patients (n=91),
and 10.0+/-2.5cm in young adult females (n=10). CONCLUSION: Percutaneous trans
catheter ASD closure was safely performed under the support of a surgical team.
The cosmetic outcome of surgical closure is improving after initiation of partial
sternotomy via limited skin incision for the pediatric population and young adult
females. Prior to the treatment, the physicians must thoroughly inform patients
and families of the advantages and disadvantages of both treatment options.
PMID- 25113953
TI - Genotyping of exons 1 to 20 in Duchenne muscular dystrophy by universal multiplex
PCR and short-end capillary electrophoresis.
AB - One rapid CE method was established to diagnose Duchenne muscular dystrophy
(DMD). DMD is a severe recessive inherited disorder frequently caused by gene
deletions. Among them, exons 1-20 account for nearly 30% of occurrences. In this
study, the universal multiplex PCR was used to enhance the fluorescently labeling
efficiency, which was performed only by one universal fluorescent primer. After
PCR, a short-end injection CE (short-end CE) speeded up the genotyping of the DMD
gene. This method involved no extra purification, and was completed within 9 min.
The CE conditions contained a polymer solution of 1.5% hydroxylethylcellulose in
1* TBE buffer at 6 kV for separation. This method was applied to test six DMD
patients and one healthy male person. The results showed good agreement with
those of multiplex ligation-dependent probe amplification. This method can be
applied for clinical diagnosis of DMD disease. Accurate diagnosis of the DMD gene
is the best way to prevent the disease.
PMID- 25113952
TI - Results of catheter ablation of atrial fibrillation in hypertrophied hearts -
Comparison between primary and secondary hypertrophy.
AB - BACKGROUND AND PURPOSE: Approximately 20-25% of the patients with hypertrophic
cardiomyopathy (HCM) develop atrial fibrillation (AF) during the clinical course
of the disease, a percentage significantly larger than that of the general
population. The purpose of the present study was to report on the procedural
results of patients with AF and either primary or secondary left ventricular
hypertrophy (LVH). METHODS AND SUBJECTS: Twenty-two consecutive HCM patients (55%
male, mean age 57+/-8 years) with symptomatic AF, having undergone AF ablation
procedures between September 2009 and July 2012 were compared with respect to
procedural outcome and follow-up characteristics with 22 matched controls with
secondary cardiac hypertrophy (64% male, 63+/-10 years) from our prospective AF
catheter ablation registry. RESULTS AND CONCLUSION: Radiofrequency catheter
ablation (RFCA) was successful in restoring long-term sinus rhythm in patients
with LVH due to HCM and due to secondary etiology. However, patients with HCM
needed more RFCA procedures and frequently additional antiarrhythmic drug therapy
in order to maintain sinus rhythm.
PMID- 25113954
TI - Two distinct neural mechanisms in early visual cortex determine subsequent visual
processing.
AB - Neuroscience research has conventionally focused on how the brain processes
sensory information, after the information has been received. Recently, increased
interest focuses on how the state of the brain upon receiving inputs determines
and biases their subsequent processing and interpretation. Here, we investigated
such 'pre-stimulus' brain mechanisms and their relevance for objective and
subjective visual processing. Using non-invasive focal brain stimulation
[transcranial magnetic stimulation (TMS)] we disrupted spontaneous brain state
activity within early visual cortex (EVC) before onset of visual stimulation, at
two different pre-stimulus-onset-asynchronies (pSOAs). We found that TMS pulses
applied to EVC at either 20 msec or 50 msec before onset of a simple orientation
stimulus both prevented this stimulus from reaching visual awareness.
Interestingly, only the TMS-induced visual suppression following TMS at a pSOA of
?20 msec was retinotopically specific, while TMS at a pSOA of ?50 msec was not.
In a second experiment, we used more complex symbolic arrow stimuli, and found
TMS-induced suppression only when disrupting EVC at a pSOA of ? ?60 msec, which,
in line with Experiment 1, was not retinotopically specific. Despite this
topographic unspecificity of the ?50 msec effect, the additional control
measurements as well as tracking and removal of eye blinks, suggested that also
this effect was not the result of an unspecific artifact, and thus neural in
origin. We therefore obtained evidence of two distinct neural mechanisms taking
place in EVC, both determining whether or not subsequent visual inputs are
successfully processed by the human visual system.
PMID- 25113955
TI - Relevance of subcortical visual pathways disruption to visual symptoms in
dementia with Lewy bodies.
AB - Visual hallucinations represent a core diagnostic criterion for dementia with
Lewy bodies (DLB). We hypothesized that thalamic regions, which are critically
involved in the modulation of visual transmission, may be differentially
disrupted in DLB as compared to Alzheimer's Disease (AD) and that these deficits
could relate to visual dysfunction in DLB patients. Magnetic Resonance and
Diffusion Tensor Imaging (DTI) were performed with a 3 T scanner on a sample
population of 15 DLB patients, 15 AD patients and 13 healthy volunteers. Regional
thalamic micro-structural changes were assessed by parcelling the thalamus based
on its connectivity to cortex and to amygdala and by measuring the mean
diffusivity (MD) in each connectivity-defined sub-region. Micro-structural grey
matter damage associated to higher MD values was found bilaterally in DLB
compared to controls in the sub-regions projecting from thalamus to prefrontal
and parieto-occipital cortices. Right thalamic sub-region projecting to amygdala
and left thalamic sub-region projecting to motor cortex were also affected in DLB
compared to controls. Higher MD values were found bilaterally in AD compared to
controls in the thalamic sub-regions projecting to temporal cortex. Specific
comparison between the two forms of dementia found differences: the sub-regions
which project from thalamus to parieto-occipital cortex and to amygdala showed
higher MD values in DLB compared to AD patients. In DLB patients, correlation
analysis showed a significant correlation between NPI hallucinations item scores
and MD values in the right thalamic sub-regions projecting to parietal and
occipital cortices. The present study demonstrates how thalamic connectivity
alterations between higher and lower visual areas may be relevant in explaining
visual hallucinations in DLB.
PMID- 25113956
TI - Impact of spinal dysraphism on urinary and faecal prognosis in 25 cases of
cloacal malformation.
AB - OBJECTIVE: Urinary and faecal continence are key challenges goal of cloacal
malformation management. Most well-known prognostic factors are the length of
common channel (CC) and the presence of a sacral defect, but the impact of
associated spinal dysraphism is less well documented. The aim of this study was
to investigate the impact of different types of dysraphism on urinary and faecal
continence in this patient population. MATERIALS AND METHODS: From 1991 to 2011,
charts and office notes of 25 patients with cloacal malformation were
retrospectively reviewed. At last clinic visit, urinary and faecal continence
status according to Krickenbeck criteria were correlated with the length of CC,
the presence of a sacral defect (sacral ratio), and the presence of different
types of spinal cord dysraphism using magnetic resonance imaging (MRI) and
Fisher's exact test. RESULTS: Mean follow-up was 8 years (4 months-21 years). The
sacral ratio was abnormal (below 0.74) in 18 cases out of 25 (72%). MRI review
showed normal spinal cord in eight out of 23 cases (Group 1), spinal cord anomaly
in 15 out of 23 cases (65%) including nine cases of tethered cord complex (Group
2) and six cases of a short spinal cord (Group 3). While statistical analysis
showed a difference regarding urinary prognosis between the groups (p=0.005), no
significant difference was found regarding faecal prognosis. None of the six
patients with short spinal cord were continent for both urinary and faecal
prognosis. CONCLUSIONS: This is the first study, which highlights the impact of
different types of spinal dysraphism on functional outcome in patients with
cloaca. Short spinal cord seemed to carry the worst prognosis. A prospective
study with a larger series is mandatory to confirm these preliminary results.
PMID- 25113957
TI - Methodological approaches and magnitude of the clinical unmet need associated
with amotivation in mood disorders.
AB - BACKGROUND: There is growing research interest in studying motivational deficits
in different neuropsychiatric disorders because these symptoms appear to be more
common than originally reported and negatively impact long-term functional
outcomes. However, there is considerable ambiguity in the terminology used to
describe motivational deficits in the scientific literature. For the purposes of
this manuscript, the term "amotivation" will be utilised in the context of mood
disorders, since this is considered a more inclusive/appropriate term for this
patient population. Other challenges impacting the study of amotivation in mood
disorders, include: appropriate patient population selection; managing or
controlling for potential confounding factors; the lack of gold-standard
diagnostic criteria and assessment scales; and determination of the most
appropriate study duration. METHODS: This paper summarises the search for a
consensus by a group of experts in the optimal approach to studying amotivation
in mood disorders. RESULTS: The consensus of this group is that amotivation in
mood disorders is a legitimate therapeutic target, given the magnitude of the
associated unmet needs, and that proof-of-concept studies should be conducted in
order to facilitate subsequent larger investigations. The focus of this
manuscript is to consider the study of amotivation, as a residual symptom of
major depressive disorder (MDD) or bipolar depression (BD), following adequate
treatment with a typical antidepressant or mood stabiliser/antipsychotic,
respectively. DISCUSSION: There is a paucity of data studying amotivation in mood
disorders. This manuscript provides general guidance on the most appropriate
study design(s) and methodology to assess potential therapeutic options for the
management of residual amotivation in mood disorders.
PMID- 25113959
TI - Obsessive-compulsive symptoms and personal disposition, family coherence and
school environment in Chinese adolescents: a resilience approach.
AB - BACKGROUND: Risk factors of adolescents with obsessive-compulsive symptoms (OC)
have been extensively examined, but protective resilience factors have not been
explored, particularly in Chinese adolescents. AIM: This study aimed to
investigate the association of resilience factors with the occurrence of OC and
its symptoms in Chinese adolescents. METHOD: This study consisted of two phases.
The first phase used a cross-sectional design involving a stratified clustered
non-clinical sample of 3185 secondary school students. A clinical interview
procedure was then employed to diagnose OC in students who had a Leyton
Obsessional Inventory 'yes' score of >=15. The second phase used a case-control
study design to analyse the relationship between resilience factors and OC in a
matched sample of 288 adolescents with diagnosed OC relative to 246 healthy
adolescents. RESULTS: Low personal disposition scores in self-fulfilment,
flexibility and self-esteem, and low peer relation scores in the school
environment were associated with a higher probability of having OC. Canonical
correlation analysis indicated that OC symptoms were significantly associated
with personal dispositions, poor peer relationships and maladaptive social life,
but not to family coherence. LIMITATIONS: The study is not prospective in nature,
so the causal relationship between OC occurrence and resilience factors cannot be
confirmed. Second, the use of self-report instruments in personal disposition,
family coherence, and school environment may be a source of error. CONCLUSIONS:
Resilience factors at both the personal disposition and school environment levels
are important predictors of OC symptoms and caseness. Future studies using
prospective designs are needed to confirm these relationships.
PMID- 25113958
TI - "Someone like us": delivering maternal mental health through peers in two South
Asian contexts.
AB - BACKGROUND: Peer-led psychosocial interventions are one solution to address the
great paucity of skilled mental health human resources in South Asia. The aim of
this study was to explore peer-delivered care for maternal depression in two
diverse contexts in South Asia. METHODS: The study was carried out in the urban
setting of Goa, India and rural setting in Rawalpindi, Pakistan. In total, 61 in
depth interviews (IDIs) and 3 focus group discussions (FGDs), and 38 IDIs and 10
FGDs, were conducted with multiple stakeholders in urban Goa and rural Rawalpindi
respectively. We used the framework approach to analyze data. RESULTS: Peers from
the same community were the most preferred delivery agents of a community-based
psychosocial intervention in both sites. There were contextual similarities and
differences between the two sites. Preferred characteristics among peers included
local, middle-aged, educated mothers with similar experiences to participants,
good communication skills and a good character. Key differences between the two
contexts included a greater emphasis on the peer's family social standing in
rural Rawalpindi and financial incentives as motivators for individual peers in
urban Goa. LIMITATIONS: Generalizability of our findings is limited to two
specific contexts in a vast and diverse region. DISCUSSION: Our study
demonstrates that peers have the potential to deliver maternal psychosocial
interventions in low-income settings. There are contextual differences in the
preferred characteristics and motivators between the sites, and these should be
carefully considered in program implementation.
PMID- 25113960
TI - Characteristics of deaths by suicide in Northern Ireland from 2005 to 2011 and
use of health services prior to death.
AB - BACKGROUND: Service presentation may offer an opportunity for intervention prior
to suicide. The study aimed to examine the characteristics, disorders and service
use profiles of those who had died by suicide in Northern Ireland (NI) from 2005
to 2011. METHODS: An analysis of a database of deaths by suicide and undetermined
intent based on data in the NI Coronial files from 2005 to 2011 (N=1667).
RESULTS: Males are three times as likely to die by suicide as females and suicide
rates similar among those aged 20-60 years. Females have increased service use
prior to suicide; males tend to disengage with services prior to death. Females
are more likely to have recorded prior attempts, service use, diagnosis and
referral. The most common health service used was primary care. LIMITATIONS:
Despite the inclusion of undetermined deaths (probable suicides) a proportion of
deaths by suicide remain unrecorded as such. Data on marital status and mental
and physical disorders were based on information recorded by police officers from
relatives, other informants and medical records. The reliability of this data may
therefore be questioned. CONCLUSIONS: Primary care has an important role in
suicide prevention. Gendered patterns in service use prior to death should be
considered in suicide prevention programmes. It is important to strengthen
clinicians' knowledge of the manifestations of suicidal ideation in males and
ways of encouraging service use in males. The NI population who were exposed to
the height of the violence of the conflict appear to be at increased risk of
suicide as they age.
PMID- 25113961
TI - [Mortality in patients with infective endocarditis treated in 2 different centers
with on-site cardiac surgery. Reply].
PMID- 25113962
TI - Anti-lymphoproliferative activity of alpha-2-macroglobulin in the plasma of
hibernating 13-lined ground squirrels and woodchucks.
AB - Plasma from hibernating (HIB) woodchucks (Marmota monax) or 13-lined ground
squirrels (Ictidomys tridecemlineatus) suppressed (3)H-thymidine uptake in mouse
spleen cell cultures stimulated with Concanavalin A (ConA); plasma from non
hibernating animals were only slightly inhibitory. Maximum inhibition occurred
when HIB plasma was added to the cultures prior to ConA. After HPLC size
exclusion chromatography of the HIB ground squirrel plasma, a single fraction
(fraction-14) demonstrated inhibitory activity. Assay of fraction-14 from 8 HIB
squirrels showed inhibition ranging from 13 to 95%; inhibition was correlated to
the time the squirrels were exposed to cold prior to hibernation. Western blot
analysis showed the factor to be a large molecular weight protein (>300 kDa), and
mass spectrometry identified sequences that were 100% homologous with alpha-2
macroglobulin from humans and other species. These findings indicate a
hibernation-related protein that may be responsible for immune system down
regulation.
PMID- 25113963
TI - Pex11a deficiency is associated with a reduced abundance of functional
peroxisomes and aggravated renal interstitial lesions.
AB - Although proteinuria is known to be associated with the deterioration of chronic
kidney disease, the molecular basis of this mechanism is not fully understood. We
previously found that Pex11a deficiency was associated with a reduction of
functional peroxisomes and impaired fatty acid metabolism in hepatocytes and
resulted in steatosis. Proximal tubule cells are rich in peroxisomes. We assessed
whether Pex11a deficiency might result in the derangement of peroxisome systems
in proximal tubule cells and the aggravation of tubulointerstitial lesions in
chronic kidney disease. Histological analyses showed that the number of
functional peroxisomes in proximal tubule cells was reduced in Pex11a knockout
(Pex11a(-/-)) mice. To clarify whether a decrease in the number of tubular
peroxisomes might aggravate interstitial lesions, we assessed 2 models in which
proximal tubule cells are overloaded with fatty acids (ie, deoxycorticosterone
acetate and salt hypertension and the overload of fatty acid-bound albumin).
Deoxycorticosterone acetate -salt-treated Pex11a(-/-) mice exhibited greater
interstitial lesions than deoxycorticosterone acetate-salt-treated wild-type mice
in terms of tubular lipid accumulation, blood pressure, urinary albumin, urinary
N-acetyl-beta-d-glucosaminidase, urinary 8-iso-prostane, and the histological
evaluation of fibrosis and inflammation. An overload of fatty acid-bound albumin
also resulted in more severe tubulointerstitial lesions in Pex11a(-/-) mice than
in wild-type mice. Fenofibrate, a peroxisome proliferator-activated receptor
alpha agonist, restored the abundance of peroxisomes and reduced the
tubulointerstitial lesions induced by deoxycorticosterone acetate-salt
hypertension. In conclusion, our results indicate that proximal tubule
peroxisomes play an important role in proteinuria-induced interstitial lesions.
The activation of tubular peroxisomes might be an excellent therapeutic strategy
against chronic kidney disease.
PMID- 25113965
TI - If I had resistant hypertension.
PMID- 25113966
TI - The influence of speaker and listener variables on intelligibility of dysarthric
speech.
AB - This study compared changes in speech clarity as a function of speaking context.
It is well documented that words produced in sentence contexts yield higher
intelligibility than words in isolation for speakers with mild to moderate
dysarthria. To tease apart the effect of speaker and listener variables, the
current study aimed to quantify differences in word intelligibility by speaking
task. Eighteen speakers with dysarthria produced a set of 25 words in isolation
and within the context of a sentence. Eighteen listeners heard a randomized
sample of the isolated productions, single words extracted from the sentences,
and the full unaltered sentences. Listeners transcribed what they heard and rated
their confidence. Words produced in isolation were just as intelligible as words
produced in sentence context, both of which were more intelligible than extracted
words. In other words, speakers reduced articulatory clarity in sentence
production compared to isolated productions; listeners were able to cope with
this reduction in clarity when they had access to contextual information but not
when these cues were removed in the extracted condition. These findings are
consistent with Lindblom's hypo-hyperarticulation theory in that adults with
dysarthria appear to be modulating articulatory precision based on listener/task
variables. This work has implications for clinical practice in that isolated word
and sentence production tasks yielded equivalent intelligibility findings.
LEARNING OUTCOMES: Readers will recognize that speech intelligibility is
influenced by speaker and listener variables and thus the choice of speaking and
listening task may yield different results. Commonly held clinical belief is that
sentence production tasks yield inflated intelligibility scores but we did not
find that in this sample. Findings also indicate that speakers with dysarthria
may modulate articulatory clarity in response to listener needs which should be
considered in treatment planning.
PMID- 25113964
TI - WNK-SPAK-NCC cascade revisited: WNK1 stimulates the activity of the Na-Cl
cotransporter via SPAK, an effect antagonized by WNK4.
AB - The with-no-lysine (K) kinases, WNK1 and WNK4, are key regulators of blood
pressure. Their mutations lead to familial hyperkalemic hypertension (FHHt),
associated with an activation of the Na-Cl cotransporter (NCC). Although it is
clear that WNK4 mutants activate NCC via Ste20 proline-alanine-rich kinase, the
mechanisms responsible for WNK1-related FHHt and alterations in NCC activity are
not as clear. We tested whether WNK1 modulates NCC through WNK4, as predicted by
some models, by crossing our recently developed WNK1-FHHt mice (WNK1(+/FHHt))
with WNK4(-/-) mice. Surprisingly, the activated NCC, hypertension, and
hyperkalemia of WNK1(+/FHHt) mice remain in the absence of WNK4. We demonstrate
that WNK1 powerfully stimulates NCC in a WNK4-independent and Ste20 proline
alanine-rich kinase-dependent manner. Moreover, WNK4 decreases the WNK1 and WNK3
mediated activation of NCC. Finally, the formation of oligomers of WNK kinases
through their C-terminal coiled-coil domain is essential for their activity
toward NCC. In conclusion, WNK kinases form a network in which WNK4 associates
with WNK1 and WNK3 to regulate NCC.
PMID- 25113967
TI - Interactions with John Gurdon--muscle as a mesodermal read-out and the community
effect.
AB - John Gurdon has made major contributions to developmental biology in addition to
his Nobel prize winning work on nuclear reprogramming. With the frog, Xenopus, as
a vertebrate model, his work on mesoderm induction led him to identify a
community effect required for tissue differentiation after progenitor cells have
entered a specific mesodermal programme. It is in the context of this
biologically important concept, with myogenesis as an example, that we have had
most scientific exchanges. Here I trace my contacts with him, from an interest in
histone regulation of gene expression and reprogramming, to myogenic
determination factors as markers of early mesodermal induction, to the role of
the community effect in the spatiotemporal control of skeletal muscle formation.
I also recount some personal anecdotes from encounters in Oxford, Paris and
Cambridge, to illustrate my appreciation of him as a scientist and a colleague.
PMID- 25113968
TI - Impact of urbanization level on urban air quality: a case of fine particles
(PM(2.5)) in Chinese cities.
AB - We examined and compared PM2.5 concentrations in urban and the surrounding
regions, and further investigated the impact of urbanization on urban PM2.5
concentrations at the Chinese prefectures. Annual PM2.5 concentrations in most
prefectures were greater than 10 MUg/m(3), the air quality guideline of the World
Health Organization. Those prefectures were mainly distributed along the east
coast and southeast of Sichuan province; The urban PM2.5 concentrations (
[Formula: see text] ) in 85 cities were greater than (>10 MUg/m(3)) those in the
surrounding area. Those cities were mainly located in the Beijing-Sichuan and
Shanghai-Guangxi belts. In addition, [Formula: see text] was less than (<0
MUg/m(3)) that in surrounding areas in only 41 prefectures, which were located in
western China or nearby mega cities; Significant positive correlations were found
between [Formula: see text] and urban population (R(2) = 0.99, P < 0.05), and
between [Formula: see text] and urban second industry fraction (R(2) = 0.71, P <
0.05), suggesting that urbanization had considerable impact on PM2.5
concentrations.
PMID- 25113969
TI - Pathological mechanisms underlying aneurysmal subarachnoid haemorrhage and
vasospasm.
AB - Aneurysmal subarachnoid haemorrhage is a cerebrovascular disease associated with
an overall mortality as high as 50%. Delayed ischaemic neurologic deficits are a
major contributor to this statistic, as well as the significant morbidity
associated with the disease. Studies examining the pathophysiologic events
causing these devastating changes in cerebral blood flow have identified several
mechanisms which are thought to contribute to the development of delayed
ischaemic neurological deficits, perhaps the most damaging of which are increased
intracranial pressure and cerebral vasospasm. In addition, the presence of blood
in the subarachnoid space can trigger a myriad of reactions resulting in
increased capillary permeability, breakdown of the blood-brain barrier, and
inflammation in surrounding neural tissue that adds to the devastating effects of
haemorrhage. A detailed understanding of the post-haemorrhagic cellular and
molecular changes that contribute to the development of cerebral ischaemia and
vasospasm is imperative to the formulation of treatment and prevention options
for subarachnoid haemorrhage patients. Despite a large body of research within
this field, a complete understanding of rupture and vasospasm remains elusive.
This study reviews the role of vasoactive substances, such as endothelin-1, as
well as the histochemistry and molecular pathology of post-haemorrhage
inflammation in the development of vasospasm and cerebral ischaemia.
PMID- 25113971
TI - Retraction. The requirements for natural Th17 cell development are distinct from
those of conventional Th17 cells.
PMID- 25113970
TI - Nfil3 is crucial for development of innate lymphoid cells and host protection
against intestinal pathogens.
AB - The bZIP transcription factor Nfil3 (also known as E4BP4) is required for the
development of natural killer (NK) cells and type 1 innate lymphoid cells
(ILC1s). We find that Nfil3 plays a critical role in the development of other
mucosal tissue-associated innate lymphocytes. Type 3 ILCs (ILC3s), including
lymphoid tissue inducer (LTi)-like cells, are severely diminished in both numbers
and function in Nfil3-deficient mice. Using mixed bone marrow chimeric mice, we
demonstrate that Nfil3 is critical for normal development of gut-associated ILC3s
in a cell-intrinsic manner. Furthermore, Nfil3 deficiency severely compromises
intestinal innate immune defense against acute bacterial infection with
Citrobacter rodentium and Clostridium difficile. Nfil3 deficiency resulted in a
loss of the recently identified ILC precursor, yet conditional ablation of Nfil3
in the NKp46(+) ILC3 subset did not perturb ILC3 numbers, suggesting that Nfil3
is required early during ILC3 development but not for lineage maintenance.
Lastly, a marked defect in type 2 ILCs (ILC2s) was also observed in the lungs and
visceral adipose tissue of Nfil3-deficient mice, revealing a general requirement
for Nfil3 in the development of all ILC lineages.
PMID- 25113973
TI - Interplay between regulatory T cells and PD-1 in modulating T cell exhaustion and
viral control during chronic LCMV infection.
AB - Regulatory T (T reg) cells are critical for preventing autoimmunity mediated by
self-reactive T cells, but their role in modulating immune responses during
chronic viral infection is not well defined. To address this question and to
investigate a role for T reg cells in exhaustion of virus-specific CD8 T cells,
we depleted T reg cells in mice chronically infected with lymphocytic
choriomeningitis virus (LCMV). T reg cell ablation resulted in 10-100-fold
expansion of functional LCMV-specific CD8 T cells. Rescue of exhausted CD8 T
cells was dependent on cognate antigen, B7 costimulation, and conventional CD4 T
cells. Despite the striking recovery of LCMV-specific CD8 T cell responses, T reg
cell depletion failed to diminish viral load. Interestingly, T reg cell ablation
triggered up-regulation of the molecule programmed cell death ligand-1 (PD-L1),
which upon binding PD-1 on T cells delivers inhibitory signals. Increased PD-L1
expression was observed especially on LCMV-infected cells, and combining T reg
cell depletion with PD-L1 blockade resulted in a significant reduction in viral
titers, which was more pronounced than that upon PD-L1 blockade alone. These
results suggest that T reg cells effectively maintain CD8 T cell exhaustion, but
blockade of the PD-1 inhibitory pathway is critical for elimination of infected
cells.
PMID- 25113972
TI - Dissecting the complement pathway in hepatic injury and regeneration with a novel
protective strategy.
AB - Liver resection is commonly performed under ischemic conditions, resulting in two
types of insult to the remnant liver: ischemia reperfusion injury (IRI) and loss
of liver mass. Complement inhibition is recognized as a potential therapeutic
modality for IRI, but early complement activation products are also essential for
liver regeneration. We describe a novel site-targeted murine complement
inhibitor, CR2-CD59, which specifically inhibits the terminal membrane attack
complex (MAC), and we use this protein to investigate the complement-dependent
balance between liver injury and regeneration in a clinical setting of
pharmacological inhibition. CR2-CD59 did not impact in vivo generation of C3 and
C5 activation products but was as effective as the C3 activation inhibitor CR2
Crry at ameliorating hepatic IRI, indicating that the MAC is the principle
mediator of hepatic IRI. Furthermore, unlike C3 or C5 inhibition, CR2-CD59 was
not only protective but significantly enhanced hepatocyte proliferation after
partial hepatectomy, including when combined with ischemia and reperfusion.
Remarkably, CR2-CD59 also enhanced regeneration after 90% hepatectomy and
improved long-term survival from 0 to 70%. CR2-CD59 functioned by increasing
hepatic TNF and IL-6 levels with associated STAT3 and Akt activation, and by
preventing mitochondrial depolarization and allowing recovery of ATP stores.
PMID- 25113974
TI - Tight regulation of ubiquitin-mediated DNA damage response by USP3 preserves the
functional integrity of hematopoietic stem cells.
AB - Histone ubiquitination at DNA breaks is required for activation of the DNA damage
response (DDR) and DNA repair. How the dynamic removal of this modification by
deubiquitinating enzymes (DUBs) impacts genome maintenance in vivo is largely
unknown. To address this question, we generated mice deficient for Ub-specific
protease 3 (USP3; Usp3Delta/Delta), a histone H2A DUB which negatively regulates
ubiquitin-dependent DDR signaling. Notably, USP3 deletion increased the levels of
histone ubiquitination in adult tissues, reduced the hematopoietic stem cell
(HSC) reserves over time, and shortened animal life span. Mechanistically, our
data show that USP3 is important in HSC homeostasis, preserving HSC self-renewal,
and repopulation potential in vivo and proliferation in vitro. A defective DDR
and unresolved spontaneous DNA damage contribute to cell cycle restriction of
Usp3Delta/Delta HSCs. Beyond the hematopoietic system, Usp3Delta/Delta animals
spontaneously developed tumors, and primary Usp3Delta/Delta cells failed to
preserve chromosomal integrity. These findings broadly support the regulation of
chromatin ubiquitination as a key pathway in preserving tissue function through
modulation of the response to genotoxic stress.
PMID- 25113975
TI - Increased severity of respiratory infections associated with elevated anti-LPS
IgG2 which inhibits serum bactericidal killing.
AB - Although specific antibody induced by pathogens or vaccines is a key component of
protection against infectious threats, some viruses, such as dengue, induce
antibody that enhances the development of infection. In contrast, antibody
dependent enhancement of bacterial infection is largely unrecognized. Here, we
demonstrate that in a significant portion of patients with bronchiectasis and
Pseudomonas aeruginosa lung infection, antibody can protect the bacterium from
complement-mediated killing. Strains that resist antibody-induced, complement
mediated killing produce lipopolysaccharide containing O-antigen. The inhibition
of antibody-mediated killing is caused by excess production of O-antigen-specific
IgG2 antibodies. Depletion of IgG2 to O-antigen restores the ability of sera to
kill strains with long-chain O-antigen. Patients with impaired serum-mediated
killing of P. aeruginosa by IgG2 have poorer respiratory function than infected
patients who do not produce inhibitory antibody. We suggest that excessive
binding of IgG2 to O-antigen shields the bacterium from other antibodies that can
induce complement-mediated killing of bacteria. As there is significant sharing
of O-antigen structure between different Gram-negative bacteria, this IgG2
mediated impairment of killing may operate in other Gram-negative infections.
These findings have marked implications for our understanding of protection
generated by natural infection and for the design of vaccines, which should avoid
inducing such blocking antibodies.
PMID- 25113976
TI - Aroclor 1254-induced genotoxicity in male gonads through oxidatively damaged DNA
and inhibition of DNA repair gene expression.
AB - The present study aimed to examine if multiple exposure to Aroclor 1254, a
commercial mixture of polychlorinated biphenyls, had any genotoxic potential on
gonads of male mice; moreover, the molecular mechanism(s) underlying this
deleterious effects were elucidated. In the standard comet assay, there were
significant increases in the incidence of DNA strand breaks in sperm of mice
killed after 3 and 24h of last treatment with 4 mg/kg/day Aroclor 1254 for 5
weeks, while no significant difference in the DNA strand breaks was found in mice
treatment with 1 and 2 mg/kg/day Aroclor 1254. The same results were also
observed with spermatocyte chromosomal analysis as obvious aberrant primary
spermatocytes were noted with the highest dose of Aroclor 1254 when testes were
examined at 24h after the last exposure. Moreover, digestion with EndoIII
resulted in significantly increased levels of DNA damage at 3 and 24h after the
last exposure to 2mg/kg/day Aroclor 1254; digestion with Fpg resulted in a
significant increase in DNA damage at the 3-h sampling time only as detected by
oxidative comet assays. The expression of DNA repair genes p53, PARP1 and BAX
were up-regulated in testes of mice killed after 3 and 24h of last administration
of 4 mg/kg/day Aroclor 1254. On the other hand, no significant alteration in the
expression of XRCC1 gene was observed at both sampling times. It is noteworthy
that the expression of OGG1 and APEX1 was significantly decreased at 3h after the
last exposure to 4 mg/kg/day Aroclor 1254. On the other hand, only the expression
level of APEX1 was recovered at the 24-h sampling times. The unrecovered OGG1 may
suggest that inhibition of DNA repair can be considered as a potential mode of
action of Aroclor 1254 gonadal toxicity and carcinogenesis.
PMID- 25113978
TI - The life cycle and occurrence of Haemaphysalis concinna (Acari: Ixodidae) under
field conditions.
AB - The life cycle and occurrence of Haemaphysalis concinna were investigated under
field conditions from April 2012 to March 2013 in Eerguna National Natural
Reserve Area situated on the China-Russia border in Inner Mongolia, China. Under
natural conditions, the whole life cycle of H. concinna was allowed to complete
in a natural tick habitat. With domestic rabbits supplied as hosts, the seasonal
occurrence and behaviors of H. concinna were also observed in the field plot
which was chosen in a natural tick habitat from April to October 2012. Results
indicated that the durations of the life cycle from unfed adults to the next
generation unfed adults of H. concinna ranged from 124 to 186 days (average
periods of 153.1 days). The incubation time of eggs ranged from 39 to 57 days
(average periods of 41.3 days), which is the longest period among the four
developmental stages, followed by the premolt periods for larvae (averaged 37.7
days) and nymphs (averaged 26.0 days). The number of eggs was positively
correlated with the weight of engorged females (r=0.8562, p<0.001). Eggs were
laid in high amounts in the first week, subsequently, the egg amount declined
gradually with small peaks occasionally observed. The female reproductive
efficiency index (REI) and reproductive fitness index (RFI) was 6.2 and 4.3,
respectively. Observations on the occurrence of H. concinna indicated that, in
the confined plot under field conditions, larvae appeared in late May and peaked
in early July, and nymphs were active during July and August. Therefore, there
was an overlap in the occurrence of larvae and nymphs in both June and July.
PMID- 25113977
TI - Blood feeding on large grazers affects the transmission of Borrelia burgdorferi
sensu lato by Ixodes ricinus.
AB - The presence of Ixodes ricinus and their associated Borrelia infections on large
grazers was investigated. Carcases of freshly shot red deer, mouflon and wild
boar were examined for the presence of any stage of I. ricinus. Questing ticks
were collected from locations where red deer and wild boar are known to occur.
Presence of Borrelia burgdorferi s.l. DNA was examined in a fraction of the
collected ticks. Larvae, nymphs and adult ticks were found on the three large
grazers. Red deer had the highest tick burden, with many of the nymphs and adult
females attached for engorgement. Most larvae had not attached. The mean number
of ticks on the animals varied from 13 to 67. Ticks were highly aggregated
amongst the animals: some animals had no ticks, while others had high numbers.
Larvae and nymphs were mostly found on the ears, while adult ticks were attached
to the axillae. The Borrelia infection rate of questing nymphs was 8.5%.
Unengorged wandering nymphs on deer had a Borrelia infection rate of 12.5%, while
only 0.9% of feeding nymphs carried a Borrelia infection. The infection rate of
unengorged adult male ticks was 4.5%, and that of feeding female ticks was 0.7%.
The data suggest that ticks feeding on red deer and wild boar lose their Borrelia
infections. The implications of the results are discussed with respect to
Borrelia epidemiology and maintenance of a Borrelia reservoir as well as the role
of reproductive hosts for Ixodes ricinus.
PMID- 25113979
TI - Genetic variability of Anaplasma phagocytophilum in ticks and voles from Ixodes
persulcatus/Ixodes trianguliceps sympatric areas from Western Siberia, Russia.
AB - Anaplasma phagocytophilum is a causative agent of granulocytic anaplasmosis in
different mammals. The presence of A. phagocytophilum was assayed in Ixodes
persulcatus, Ixodes trianguliceps ticks and Myodes spp. voles from two I.
persulcatus/I. trianguliceps sympatric areas in the Omsk region (Western Siberia,
Russia). In total, A. phagocytophilum was found in 42/108 (38.9%) of vole blood
samples, 13/34 (38.2%) of I. trianguliceps ticks removed from voles, 1/12 (8.3%)
of I. persulcatus removed from voles, and 18/279 (7.2%) of questing I.
persulcatus. GroESL operon sequence analysis of positive samples revealed three
distinct A. phagocytophilum genetic groups previously identified in ticks and
mammals in Russia. Genetic group 1 was found in 6/36 (16.7%) of sequenced
positive blood samples; this group was previously revealed in I. persulcatus and
Myodes spp. voles in different regions of Russia. Genetic group 2 was found in
30/36 (83.3%) of sequenced positive blood samples and all positive I.
trianguliceps; this group was previously revealed only in Myodes spp. voles and
common shrews (Sorex araneus) in I. persulcatus/I. trianguliceps sympatric areas
in the Northern Ural. Genetic group 3 was found in all positive questing I.
persulcatus and one blood sample; this group was previously revealed in I.
persulcatus and Siberian chipmunks (Tamias sibiricus). We suppose that I.
trianguliceps is the most probable vector for A. phagocytophilum of group 2.
Analysis of the msp4 gene, intergenic region DOV1, and some other genetic loci
has shown that isolates from different genetic groups significantly differ in all
studied loci and that A. phagocytophilum of group 2 is closely related to A.
phagocytophilum isolates revealed in voles and I. trianguliceps in Europe. A.
phagocytophilum of groups 1 and 2 are the most similar to each other, while A.
phagocytophilum of group 3 clusters with European A. phagocytophilum isolates
from I. ricinus and various mammalian species.
PMID- 25113980
TI - Seasonal activity patterns of the western black-legged tick, Ixodes pacificus, in
relation to onset of human Lyme disease in northwestern California.
AB - Seasonal activity patterns of questing western black-legged ticks, Ixodes
pacificus were investigated in northwestern California. Adult I. pacificus became
active in the fall (late October/early November) and their appearance was
associated with the first rain of the season. Following a peak in January, the
abundance of adult ticks declined such that they were rare or absent by
June/July. The nymphal tick activity season occurred from January through
October, and larval activity occurred from April to June, but sometimes extended
into October. Thus, potentially infectious ticks (nymphs and adults) present a
year-round risk of Lyme disease transmission in northwestern California. The
seasonality of Lyme disease cases in humans, based on the onset of erythema
migrans, mirrored tick activity patterns and was year-round in cases infected in
California. Peak incidence in humans occurs from May through July, and indicates
that most disease transmission is from nymphal ticks. This study demonstrates
that tick activity patterns are more extended than previously recognized in
northwestern California.
PMID- 25113981
TI - In vitro isolation and infection intensity of Rickettsia parkeri in Amblyomma
triste ticks from the Parana River Delta region, Argentina.
AB - In the present study, we report the first in vitro isolation and infection
intensity of Rickettsia parkeri in Amblyomma triste ticks from Argentina. No
genetic differences in the molecular targets evaluated were found between R.
parkeri isolates from Argentina and those R. parkeri isolates reported in Uruguay
and Brazil, both obtained from A. triste. Only a minor difference was observed
when compared to R. parkeri isolated from Amblyomma maculatum from United States.
Moreover, the prevalence of infection by R. parkeri in ticks collected from the
vegetation in the Parana Delta was high (20.4%). Interestingly, the distribution
of R. parkeri infection intensity observed in A. triste ticks was distinctly
bimodal, with approximately 60% of the infected ticks presenting high rickettsial
loads (3.8*10(5)-4.5*10(7) ompA copies/tick) and the remainder with low
rickettsial levels (5.6*10(1)-6.5*10(3) ompA copies/tick). This bimodality in R.
parkeri infection intensity in ticks could determine differences in the severity
of the disease, but also be important for the infection dynamics of this
pathogen. Further research exploring the distribution of rickettsial infection
levels in ticks, as well as its determinants and implications, is warranted.
PMID- 25113982
TI - Molecular detection of tick-borne pathogens in Rhipicephalus sanguineus group
ticks.
AB - The Rhipicephalus sanguineus group includes some of the most widespread dog
ticks, whose identification currently represents a difficult task due to the
morphological similarities of these ixodid species. Recently, following the
morphological and molecular characterization of tick specimens collected from
dogs in all continents, Rhipicephalus sanguineus sensu lato (s.l.), Rhipicephalus
turanicus and three different operational taxonomic units (namely Rhipicephalus
sp. I-III) have been identified. Therefore, a comprehensive molecular study has
been herein carried out to detect selected canine vector-borne pathogens (i.e.,
Anaplasma platys, Cercopithifilaria spp., Ehrlichia canis and Hepatozoon canis)
in ticks belonging to the R. sanguineus group. A total of 204 tick specimens from
dogs were examined and identified as R. sanguineus s.l. (n=81), R. turanicus
(n=17), Rhipicephalus sp. I (n=66), Rhipicephalus sp. II (n=37), and
Rhipicephalus sp. III (n=3). PCR assays were performed to detect mitochondrial
and ribosomal target genes of Cercopithifilaria spp., A. platys, E. canis and H.
canis. Out of 204 specimens examined, 2.5%, 7.4% and 21.6% scored positive to A.
platys, H. canis and Cercopithifilaria spp., respectively. In addition, co
infections with two pathogens (i.e., Cercopithifilaria bainae and A. platys or H.
canis) were detected in four tick specimens. This study suggests a relationship
between ticks belonging to the R. sanguineus group and the geographical
distribution of A. platys, H. canis and Cercopithifilaria spp. However, the role
of each representative tick species within the R. sanguineus group in the
transmission of these canine pathogens needs to be further investigated.
PMID- 25113983
TI - Differential diagnosis of three common Ixodes spp. ticks infesting songbirds of
Western Europe: Ixodes arboricola, I. frontalis and I. ricinus.
AB - The three most common Ixodes spp. ticks found on songbirds in Western Europe are
Ixodes frontalis, I. arboricola and I. ricinus. As the latter species is a
generalist, it shares several avian hosts with the two strictly ornithophilic
species. Infestations of the three species can overlap in time and space,
implying that tick-borne pathogens maintained by the ornithophilic ticks and
their hosts could be bridged by I. ricinus to non-avian hosts. Whereas the
endophilic Ixodes arboricola only occurs in cavities, I. frontalis has been
collected frequently by flagging methods from understory vegetation, which is
also the habitat of the field-dwelling I. ricinus. As the latter two species have
rather similar morphological characteristics, they can easily be confused with
each other. In this study, we present scanning electron photomicrographs of all
developmental stages of I. arboricola and I. frontalis, and provide a
differential diagnosis key to distinguish the ornithophilic ticks from I.
ricinus. In addition, we interpreted their phylogenetic associations based on
mitochondrial 16S rDNA with other Ixodes spp. ticks (I. lividus, I. turdus, I.
brunneus, I. vespertilionis, I. trianguliceps, I. hexagonus, I. scapularis).
PMID- 25113984
TI - Taxonomic key to nymphs of the genus Amblyomma (Acari: Ixodidae) in Argentina,
with description and redescription of the nymphal stage of four Amblyomma
species.
AB - In the present study, we provide morphological descriptions of the nymph of
Amblyomma parvitarsum, A. tonelliae, and redescriptions of A. argentinae and A.
sculptum. A taxonomic key, with relevant morphological characters illustrated by
scanning electron micrographs, is provided for nymphs of the 24 species of the
genus Amblyomma occurring in Argentina. Species included are A. argentinae, A.
aureolatum, A. auricularium, A. boeroi, A. brasiliense, A. calcaratum, A.
coelebs, A. dissimile, A. dubitatum, A. incisum, A. longirostre, A. neumanni, A.
nodosum, A. ovale, A. parvitarsum, A. parvum, A. pseudoconcolor, A. pseudoparvum,
A. rotundatum, A. sculptum, A. tigrinum, A. tonelliae, A. triste and A. varium.
Principal morphological characters used for discrimination among species are
presence/absence of auriculae, cornua and festoons with tubercles, size and shape
of spurs of coxa I, margin and punctations of scutum, shape of basis capituli and
length of cervical grooves. The geographical distribution of each tick species
included in this work is presented and the importance of an accurate
determination to species level of the Amblyomma nymphs to make epidemiological
inferences is also discussed.
PMID- 25113985
TI - Peri-urbanisation, counter-urbanisation, and an extension of residential exposure
to ticks: a clue to the trends in Lyme borreliosis incidence in the Czech
Republic?
AB - The incidence of tick-borne human diseases (TBD) in the Czech Republic (CZ) is on
the increase, driven by infections increasingly acquired in residential
locations, earlier in spring and later in autumn, and among children and the
elderly. To interpret these trends, data on Lyme borreliosis (LB) incidence
between 1997 and 2010 were analysed in the context of population migration flows
registered in the CZ during the same period. Analysis showed that a migration
stream of families with children, and of the elderly, flowed from more urbanized
and densely populated localities to those more rural and less populated, where
the chance of acquiring LB in the home vicinity was greater than in the urban
settings. By contrast, a stream of people in the life phase between early
adulthood and family formation flowed reversely, corresponding to a prominent
absence of this age category from the patient spectrum. The data further showed
that the more the residential exposure became prevalent, the more people were in
year-round (rather than in summertime only) contact with ticks, which accounts
for an extension of the cases' seasonal distribution as well as for an overall
increase in case numbers. Finally, the fact that majority of the urban-to-rural
migrants could be categorised as wealthier people could explain the previously
noticed lack of low-status people among TBD patients in the CZ.
PMID- 25113986
TI - Seasonality of immature stages of Ixodes loricatus (Acari: Ixodidae) in the
Parana Delta, Argentina.
AB - In this study we analyzed seasonal trends of immature stages of Ixodes loricatus
parasitizing Akodon azarae (Sigmodontinae) in a locality of the Parana Delta,
Buenos Aires, Argentina. The data encompassed two consecutive years and the
analysis included the control of potential confounders using Generalized Linear
Mixed Models (GLMM) with a negative binomial response. Larvae had within-year
differences in abundance, but the peak months differed drastically between both
sampling years, indicating that there was no consistent seasonal pattern.
Regarding nymphs, a seasonal pattern was first apparent, but it vanished
completely when potential confounders were considered, strongly suggesting that
the association with season was spurious and caused by the confounders. Our
results showed that the occurrence of immature I. loricatus in its hosts does not
follow a distinct seasonal pattern, and highlight the usefulness of controlling
for confounding and statistically assessing consistency between years when
establishing tick seasonality.
PMID- 25113987
TI - Serological evidence of exposure to Ehrlichia canis and Anaplasma phagocytophilum
in Central Italian healthy domestic cats.
AB - The aim of the present survey was to estimate the seroprevalences of Ehrlichia
canis and Anaplasma phagocytophilum in the Central Italian feline population.
Serum samples of 560 healthy domestic cats were examined by indirect
immunofluorescence assay (IFAT), considering an antibody titre of 1:40 as cut
off. Seroprevalences of 6.4% and 4.5% were found for E. canis and A.
phagocytophilum, respectively. Adult, mixed breed cats showed seroprevalences
higher than younger and purebred subjects, whereas no differences were observed
in relation to gender and living conditions.
PMID- 25113988
TI - Prevalence of antibodies against tick-borne encephalitis virus in wild game from
Saxony, Germany.
AB - Tick-borne encephalitis (TBE) is the most important tick-transmitted viral
disease in Europe and is caused by the flavivirus TBE-virus (TBEV). In Germany
TBE is unevenly distributed with the vast majority of cases occurring in the
south in so-called risk areas defined as regions with an incidence of at least 1
case in 100,000 inhabitants. However, in low endemic areas with lesser TBE cases
the respective risk assessment is hard to achieve. We therefore intend to use the
prevalence of antibodies against TBEV in wildlife to trace TBEV endemic areas as
a surrogate marker for the notification of human cases. This study was conducted
in Saxony, Germany, where 34 autochthonous cases were reported since 2001,
thereby not allowing a geographic allocation within the state. A total of 1,851
sera from wild boar and 35 sera from roe deer from all Saxon districts shot
between April 2011 and March 2013 were screened for the presence of antibodies
against TBEV. The overall seropositivity for Saxony was 10.5%. Among the wild
boar sera, most positive samples could be found in the districts Meibetaen (23%)
and Vogtlandkreis (20%) followed by Dresden (18%), Erzgebirgskreis and Gorlitz
(both 10%). We conclude that seroprevalence studies in game animals represent a
promising surrogate marker and should be considered for future determination of
risk areas. Although we are currently unable to explain the discrepancy of the
few human cases and the high seroprevalence in some districts, vaccination
against TBE should be considered for people planning outdoor activities in
Dresden, Meibetaen or Vogtlandkreis.
PMID- 25113989
TI - Tick-borne pathogens in ticks collected from breeding and migratory birds in
Switzerland.
AB - From 2007 to 2010, 4558 migrating and breeding birds of 71 species were caught
and examined for ticks in Switzerland. A total of 1205 specimens were collected;
all were Ixodes ricinus ticks except one Ixodes frontalis female, which was found
on a common chaffinch (Fringilla coelebs) for the first time in Switzerland. Each
tick was analysed individually for the presence of Borrelia spp., Rickettsia
spp., Anaplasma phagocytophilum and tick-borne encephalitis virus (TBEV).
Altogether, 11.4% of birds (22 species) were infested by ticks and 39.8% of them
(15 species) were carrying infected ticks. Bird species belonging to the genus
Turdus were the most frequently infested with ticks and they were also carrying
the most frequently infected ticks. Each tick-borne pathogen for which we tested
was identified within the sample of bird-feeding ticks: Borrelia spp. (19.5%) and
Rickettsia helvetica (10.5%) were predominantly detected whereas A.
phagocytophilum (2%), Rickettsia monacensis (0.4%) and TBEV (0.2%) were only
sporadically detected. Among Borrelia infections, B. garinii and B. valaisiana
were largely predominant followed by B. afzelii, B. bavariensis, B. miyamotoi and
B. burgdorferi ss. Interestingly, Candidatus Neoehrlichia mikurensis was
identified in a few ticks (3.3%), mainly from chaffinches. Our study emphasizes
the role of birds in the natural cycle of tick-borne pathogens that are of human
medical and veterinary relevance in Europe. According to infection detected in
larvae feeding on birds we implicate the common blackbird (Turdus merula) and the
tree pipit (Anthus trivialis) as reservoir hosts for Borrelia spp., Rickettsia
spp. and A. phagocytophilum.
PMID- 25113992
TI - Multiple EPS interactions involved in the cohesion and structure of aerobic
granules.
AB - This study aims to clarify the biochemical nature and interactions of
Extracellular Polymeric Substances (EPS) involved in the structure and cohesive
properties of aerobic granules. Granules were incubated with selective hydrolytic
enzymes or with chemicals and the resistance of digested granules to shear stress
was evaluated. After alpha-amylase digestion, the hydrodynamic stress released
macro-particles (>315 MUm) while soluble molecules (<1.5 MUm) and micro-particles
(1.5-315 MUm) where mainly recovered after savinase and EDTA treatments. These
data show that alpha (1-4) glucans and proteins are key polymers for granule
cohesion and that divalent cationic bridging is a major aggregative mechanism. On
the basis of these experiments and microscopy observations, a model is proposed
for the spatial organization of EPS in the granular structure, in which alpha
glucans are arranged in a capsular layer surrounding bacterial clusters while
anionic proteins constitute the intercellular cement that may reinforce cohesion
inside the bacterial clusters.
PMID- 25113991
TI - Duodenal luminal nutrient sensing.
AB - The gastrointestinal mucosa is exposed to numerous chemical substances and
microorganisms, including macronutrients, micronutrients, bacteria, endogenous
ions, and proteins. The regulation of mucosal protection, digestion, absorption
and motility is signaled in part by luminal solutes. Therefore, luminal
chemosensing is an important mechanism enabling the mucosa to monitor luminal
conditions, such as pH, ion concentrations, nutrient quantity, and microflora.
The duodenal mucosa shares luminal nutrient receptors with lingual taste
receptors in order to detect the five basic tastes, in addition to essential
nutrients, and unwanted chemicals. The recent 'de-orphanization' of nutrient
sensing G protein-coupled receptors provides an essential component of the
mechanism by which the mucosa senses luminal nutrients. In this review, we will
update the mechanisms of and underlying physiological and pathological roles in
luminal nutrient sensing, with a main focus on the duodenal mucosa.
PMID- 25113993
TI - Spectrometric characterization of the effluent dissolved organic matter from an
anammox reactor shows correlation between the EEM signature and anammox growth.
AB - Anaerobic ammonium oxidation (anammox) is a cost-effective process to treat high
strength nitrogenous wastewater. Even without organic carbon input, the effluent
contains bioproducts from autotrophic and heterotrophic bacteria. In this work,
excitation-emission matrix (EEM) fluorescence spectroscopy was used to
characterize the effluent dissolved organic matter (EfOM) from an anammox reactor
treating synthetic wastewater. Two dominant EEM components were identified as
humic acid-like (component 1) and protein-like (component 2) substances with
excitation/emission peaks at <240, 355, 420/464 nm and <240, 280, 330/346 nm,
respectively. The presence of both compounds in the effluent was tracked during
an activity recovery period (nitrogen load increased from 0.2 to 1.3 kg Nm(-3)d(
1)). The effluent concentration of both components increased during this period,
indicating correlation between production and bacterial activity. The dynamics of
these bioproducts during both substrate consumption and starvation phases was
analyzed in batch experiments. Component 1 was only formed during substrate
consumption in a rate proportional to ammonium removal and was considered an up
take associated product characteristic of anammox activity. The results show that
the composition of the EfOM was qualitatively and quantitatively influenced by
process performance. Monitoring the EfOM could, therefore, offer a useful
approach to assess anammox process performance and must be further explored.
PMID- 25113994
TI - Coke dust enhances coke plant wastewater treatment.
AB - Coke plant wastewater contain many toxic pollutants. Despite physico-chemical and
biological treatment this specific type of wastewater has a significant impact on
environment and human health. This article presents results of research on
industrial adsorptive coke plant wastewater treatment. As a sorbent the coke
dust, dozen times less expensive than pulverized activated carbon, was used.
Treatment was conducted in three scenarios: adsorptive after full treatment with
coke dust at 15 g L(-1), biological treatment enhanced with coke dust at 0.3-0.5
g L(-1) and addition of coke dust at 0.3 g L(-1) prior to the biological
treatment. The enhanced biological treatment proved the most effective. It
allowed additional removal of 147-178 mg COD kg(-1) of coke dust.
PMID- 25113990
TI - EPICO 2.0 project. Development of educational therapeutic recommendations using
the DELPHI technique on invasive candidiasis in critically ill adult patients in
special situations.
AB - BACKGROUND: Although there has been an improved management of invasive
candidiasis in the last decade, still controversial issues remain, especially in
different therapeutic critical care scenarios. AIMS: We sought to identify the
core clinical knowledge and to achieve high agreement recommendations required to
care for critically ill adult patients with invasive candidiasis for antifungal
treatment in special situations and different scenarios. METHODS: Second
prospective Spanish survey reaching consensus by the DELPHI technique, conducted
anonymously by electronic e-mail in the first phase to 23 national
multidisciplinary experts in invasive fungal infections from five national
scientific societies including intensivists, anesthesiologists, microbiologists,
pharmacologists and infectious disease specialists, answering 30 questions
prepared by a coordination group after a strict review of literature in the last
five years. The educational objectives spanned four categories, including
peritoneal candidiasis, immunocompromised patients, special situations, and organ
failures. The agreement among panelists in each item should be higher than 75% to
be selected. In a second phase, after extracting recommendations from the
selected items, a meeting was held with more than 60 specialists in a second
round invited to validate the preselected recommendations. MEASUREMENTS AND MAIN
RESULTS: In the first phase, 15 recommendations were preselected (peritoneal
candidiasis (3), immunocompromised patients (6), special situations (3), and
organ failures (3)). After the second round the following 13 were validated:
Peritoneal candidiasis (3): Source control and early adequate antifungal
treatment is mandatory; empirical antifungal treatment is recommended in
secondary nosocomial peritonitis with Candida spp. colonization risk factors and
in tertiary peritonitis. Immunocompromised patients (5): consider hepatotoxicity
and interactions before starting antifungal treatment with azoles in transplanted
patients; treat candidemia in neutropenic adult patients with antifungal drugs at
least 14 days after the first blood culture negative and until normalization of
neutrophils is achieved. Caspofungin, if needed, is the echinocandin with most
scientific evidence to treat candidemia in neutropenic adult patients;
caspofungin is also the first choice drug to treat febrile candidemia; in
neutropenic patients with candidemia remove catheter. Special situations (2): in
moderate hepatocellular failure, patients with invasive candidiasis use
echinocandins (preferably low doses of anidulafungin and caspofungin) and try to
avoid azoles; in case of possible interactions review all the drugs involved and
preferably use anidulafungin. Organ failures (3): echinocandins are the safest
antifungal drugs; reconsider the use of azoles in patients under renal
replacement therapy; all of the echinocandins to treat patients under continuous
renal replacement therapy are accepted and do not require dosage adjustment.
CONCLUSIONS: Treatment of invasive candidiasis in ICU patients requires a broad
range of knowledge and skills as summarized in our recommendations. These
recommendations may help to optimize the therapeutic management of these patients
in special situations and different scenarios and improve their outcome based on
the DELPHI methodology.
PMID- 25113995
TI - Development of aptamer oligonucleotides as anticoagulants and antithrombotics for
cardiovascular diseases: current status.
AB - Aptamers are short DNA/RNA oligonucleotides selected by a process known as
Systematic Evolution of Ligands by Exponential Enrichment (SELEX) based on
affinity for target molecules. Since aptamers have several advantages over
monoclonal antibodies, such as high specificity and affinity, flexible
modification and stability, and lack of toxicity and immunogenicity, they are
promising novel diagnostic and therapeutic agents. In this review, we will
describe the development of aptamers against thrombin, von Willebrand factor
(vWF), factor IX, and factor XII as potential anticoagulants or antithrombotics
for cardiovascular diseases, especially those that have entered clinical trials.
PMID- 25114006
TI - LOX-1 and mitochondria: an inflammatory relationship.
PMID- 25114007
TI - Press imprint smear: a rapid, simple, and cheap method for the diagnosis of
cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis.
AB - A modified imprint method, Press-Imprint-Smear, was compared with histopathology
for the diagnosis of cutaneous leishmaniasis. Amastigotes were seen in 69 (92%)
of 75 individuals in one or both assays. The Press-Imprint-Smear was positive in
85.3%, and histopathology was positive in 44%. Press-Imprint-Smear is a rapid and
relatively sensitive method for the diagnosis of cutaneous leishmaniasis.
PMID- 25113996
TI - CDC42 inhibition suppresses progression of incipient intestinal tumors.
AB - Mutations in the APC or beta-catenin genes are well-established initiators of
colorectal cancer, yet modifiers that facilitate the survival and progression of
nascent tumor cells are not well defined. Using genetic and pharmacologic
approaches in mouse colorectal cancer and human colorectal cancer xenograft
models, we show that incipient intestinal tumor cells activate CDC42, an APC
interacting small GTPase, as a crucial step in malignant progression. In the
mouse, Cdc42 ablation attenuated the tumorigenicity of mutant intestinal cells
carrying single APC or beta-catenin mutations. Similarly, human colorectal cancer
with relatively higher levels of CDC42 activity was particularly sensitive to
CDC42 blockade. Mechanistic studies suggested that Cdc42 may be activated at
different levels, including at the level of transcriptional activation of the
stem cell-enriched Rho family exchange factor Arhgef4. Our results indicate that
early-stage mutant intestinal epithelial cells must recruit the pleiotropic
functions of Cdc42 for malignant progression, suggesting its relevance as a
biomarker and therapeutic target for selective colorectal cancer intervention.
PMID- 25114008
TI - Chromosomal rearrangement features of Yersinia pestis strains from natural plague
foci in China.
AB - The Yersinia pestis chromosome contains a large variety and number of insert
sequences that have resulted in frequent chromosome rearrangement events. To
identify the chromosomal rearrangement features of Y. pestis strains from five
typical plague foci in China and study spontaneous DNA rearrangements potentially
stabilized in certain lineages of Y. pestis genomes, we examined the linking mode
of locally collinear blocks (LCBs) in 30 Y. pestis strains by a polymerase chain
reaction-based method. Our results suggest most strains have relatively stable
chromosomal arrangement patterns, and these rearrangement characteristics also
have a very close relationship with the geographical origin. In addition, some
LCB linking modes are only present in specific strains. We conclude Y. pestis
chromosome rearrangement patterns may reflect the genetic features of specific
geographical areas and can be applied to distinguish Y. pestis isolates;
furthermore, most of the rearrangement events are stable in certain lineages of
Y. pestis genomes.
PMID- 25114009
TI - Standardization of a TaqMan-based real-time PCR for the detection of
Mycobacterium tuberculosis-complex in human sputum.
AB - Real-time polymerase chain reaction (qPCR) was optimized for detecting
Mycobacterium tuberculosis in sputum. Sputum was collected from patients (N =
112) with suspected pulmonary tuberculosis, tested by smear microscopy,
decontaminated, and split into equal aliquots that were cultured in Lowenstein
Jensen medium and tested by qPCR for the small mobile genetic element IS6110. The
human ERV3 sequence was used as an internal control. 3 of 112 (3%) qPCR failed.
For the remaining 109 samples, qPCR diagnosed tuberculosis in 79 of 84 patients
with culture-proven tuberculosis, and sensitivity was greater than microscopy
(94% versus 76%, respectively, P < 0.05). The qPCR sensitivity was similar (P =
0.9) for smear-positive (94%, 60 of 64) and smear-negative (95%, 19 of 20)
samples. The qPCR was negative for 24 of 25 of the sputa with negative microscopy
and culture (diagnostic specificity 96%). The qPCR had 99.5% sensitivity and
specificity for 211 quality control samples including 84 non-tuberculosis
mycobacteria. The qPCR cost ~5US$ per sample and provided same-day results
compared with 2-6 weeks for culture.
PMID- 25114010
TI - Sperm morphological features associated with chronic Chagas disease in the semen
of experimentally infected dogs.
AB - The presence of trypanosomatids in the reproductive systems of different mammals
(causing genital lesions in the acute stage of the disease) may predispose the
animals to low semen quality. However, there are no studies examining the
alterations in the sperm morphological features in the chronic stage of
Trypanosoma cruzi infection. Knowledge of these aspects is important to
understand the other ways of transmission of the Chagas disease. Progressive
motility, mass motility, concentration, and sperm morphology of 84 ejaculates of
dogs that were chronically infected with T. cruzi were evaluated. Most of the
findings were consistent with the reference values and with those obtained from
healthy control dogs. The scrotal circumference was not correlated with
spermatozoa concentration in the infected animals. In conclusion, the T. cruzi
Ninoa (MHOM/MX/1994/Ninoa) strain does not cause significant alterations in the
semen quality of dogs experiencing chronic Chagas disease (at concentrations of 5
* 10(4) to 1 * 10(6) parasites per animal).
PMID- 25114011
TI - Preliminary study on tubuloglomerular dysfunction and evidence of renal
inflammation in patients with visceral leishmaniasis.
AB - Visceral leishmaniasis (VL) is a re-emerging zoonosis of worldwide distribution.
Monocyte chemotactic protein-1 (MCP-1) and malondialdehyde (MDA) are inflammation
biomarkers that have never been investigated in VL. The aim of this study is to
investigate the association between renal abnormalities and inflammation
biomarkers in VL. This study is a preliminary prospective study with 16 VL adult
patients evaluated before treatment compared with a group of 13 healthy
volunteers and 5 VL patients evaluated after treatment. Urinary concentration and
acidification tests were performed. MCP-1 and MDA were quantified in urine.
Urinary concentration deficit was found in all VL patients before (100%) and four
VL patients after (80%) treatment. Urinary acidification deficit was found in
nine cases before (56.2%) and two cases after (40%) treatment. Urinary MCP-1 (374
+/- 359 versus 42 +/- 29 pg/mg creatinine, P = 0.002) as well as urinary MDA (5.4
+/- 2.6 versus 2.0 +/- 0.8 MUmol/mL) showed significant differences between VL
patients and controls. These data show that VL patients present urinary
concentration and acidification deficit, which can persist even after specific
treatment. Urinary MCP-1 and MDA are elevated in patients with VL, which suggests
renal inflammation and incipient renal damage.
PMID- 25114012
TI - Bacterial shedding in household contacts of cholera patients in Dhaka,
Bangladesh.
AB - Multiple Vibrio cholerae infections within the same household are common.
Household contacts of patients with cholera were observed with daily clinical
assessments and collection of rectal swab cultures for nine days after
presentation of the index case. During the follow-up period, 71 (24%) of 294
household contacts developed a positive V. cholerae rectal swab, signifying
bacterial shedding. The average length of bacterial shedding was 2.0 days (95%
confidence interval 1.7-2.4). However, 16 (5%) of 294 contacts shed V. cholerae
for >= 4 days. In a multivariate analysis, malnutrition was predictive of long
term shedding (odds ratio = 1.4, 95% confidence interval = 1.3-13, P = 0.02).
High rates of V. cholerae infection and bacterial shedding among household
contacts of cholera patients represent an opportunity for intervention to reduce
V. cholerae transmission.
PMID- 25114013
TI - Development of conventional and real-time reverse transcription polymerase chain
reaction assays to detect Tembusu virus in Culex tarsalis mosquitoes.
AB - Tembusu virus (TMUV) is an important emerging arthropod-borne virus that may
cause encephalitis in humans and has been isolated in regions of southeast Asia,
including Malaysia, Thailand, and China. Currently, detection and identification
of TMUV are limited to research laboratories, because quantitative rapid
diagnostic assays for the virus do not exist. We describe the development of
sensitive and specific conventional and real-time quantitative reverse
transcription polymerase chain reaction assays for detecting TMUV RNA in infected
cell culture supernatant and Culex tarsalis mosquitoes. We used this assay to
document the replication of TMUV in Cx. tarsalis, where titers increased 1,000
fold 5 days after inoculation. These assays resulted in the detection of virus
specific RNA in the presence of copurified mosquito nucleic acids. The use of
these rapid diagnostic assays may have future applications for field pathogen
surveillance and may assist in early detection, diagnosis, and control of the
associated arthropod-borne pathogens.
PMID- 25114015
TI - Nitrogen signalling in plant interactions with associative and endophytic
diazotrophic bacteria.
AB - Some beneficial plant-interacting bacteria can biologically fix N2 to plant
available ammonium. Biological nitrogen fixation (BNF) is an important source of
nitrogen (N) input in agriculture and represents a promising substitute for
chemical N fertilizers. Diazotrophic bacteria have the ability to develop
different types of root associations with different plant species. Among the
highest rates of BNF are those measured in legumes nodulated by endosymbionts, an
already very well documented model of plant-diazotrophic bacterial association.
However, it has also been shown that economically important crops, especially
monocots, can obtain a substantial part of their N needs from BNF by interacting
with associative and endophytic diazotrophic bacteria, that either live near the
root surface or endophytically colonize intercellular spaces and vascular tissues
of host plants. One of the best reported outcomes of this association is the
promotion of plant growth by direct and indirect mechanisms. Besides fixing N,
these bacteria can also produce plant growth hormones, and some species are
reported to improve nutrient uptake and increase plant tolerance against biotic
and abiotic stresses. Thus, this particular type of plant-bacteria association
consists of a natural beneficial system to be explored; however, the regulatory
mechanisms involved are still not clear. Plant N status might act as a key
signal, regulating and integrating various metabolic processes that occur during
association with diazotrophic bacteria. This review will focus on the recent
progress in understanding plant association with associative and endophytic
diazotrophic bacteria, particularly on the knowledge of the N networks involved
in BNF and in the promotion of plant growth.
PMID- 25114014
TI - Regulation of amino acid metabolic enzymes and transporters in plants.
AB - Amino acids play several critical roles in plants, from providing the building
blocks of proteins to being essential metabolites interacting with many branches
of metabolism. They are also important molecules that shuttle organic nitrogen
through the plant. Because of this central role in nitrogen metabolism, amino
acid biosynthesis, degradation, and transport are tightly regulated to meet
demand in response to nitrogen and carbon availability. While much is known about
the feedback regulation of the branched biosynthesis pathways by the amino acids
themselves, the regulation mechanisms at the transcriptional, post
transcriptional, and protein levels remain to be identified. This review focuses
mainly on the current state of our understanding of the regulation of the enzymes
and transporters at the transcript level. Current results describing the effect
of transcription factors and protein modifications lead to a fragmental picture
that hints at multiple, complex levels of regulation that control and coordinate
transport and enzyme activities. It also appears that amino acid metabolism,
amino acid transport, and stress signal integration can influence each other in a
so-far unpredictable fashion.
PMID- 25114017
TI - Recent recreational physical activity and breast cancer risk in postmenopausal
women in the E3N cohort.
AB - BACKGROUND: Physical activity probably protects against the risk of breast cancer
after menopause, but questions remain about how rapidly and for how long this
protective effect exists. METHODS: We analyzed data from 59,308 postmenopausal
women (2,155 incident invasive breast cancers) followed between 1993 and 2005
(8.5 years postmenopause on average) through biennial questionnaires.
Multivariable Cox models included time-varying exposure data, using levels of
recreational physical activity self-reported in 1993, 1997, and 2002. RESULTS:
Women with recent (within the previous 4 years) recreational physical activity
levels >=12 metabolic equivalent task-hours (MET-h)/week had a lower risk of
invasive breast cancer than women with lower levels [HR, 0.90; 95% confidence
interval (CI), 0.82-0.99], with no apparent dose-response relation beyond 12 MET
h/week. Associations did not vary significantly across ER/PR subtypes. Risk
reductions were of the same magnitude order regardless of weight change, body
mass index, waist circumference, or less recent (5-9 years earlier) physical
activity levels. Among women with levels of physical activity >=12 MET-h/week 5
to 9 years earlier, those who became less active (<12 MET-h/week) had a
significantly increased risk of breast cancer compared with those who did not
(HR, 1.16; 95% CI, 1.01-1.35). And, compared with the least active women at both
time points, they had no significantly decreased risk of breast cancer (HR, 1.06;
95% CI, 0.87-1.29). CONCLUSIONS: Our results suggest a decrease in risk
associated with recent recreational physical activity even of modest levels.
IMPACT: Starting or maintaining physical activity after menopause may be
beneficial regarding breast cancer risk.
PMID- 25114018
TI - Effects of coronary artery bypass grafting surgery on retinal vascular caliber,
ocular pulse amplitude and retinal thickness measurements.
AB - AIM: The retina and ocular vasculature are vulnerable to alterations in systemic
hemodynamics, such as in open heart surgeries. Our aim was to investigate retinal
vascular caliber (RVC), ocular pulse amplitude (OPA), peripapillary retinal nerve
fiber layer (RNFL) and macular thickness in coronary artery bypass grafting
(CABG) surgery patients. METHODS: Twenty-six patients who had a history of CABG
surgery and 26 age-sex-matched healthy participants were recruited for this
prospective, cross-sectional and comparative study. The RVC, peripapillary RNFL
and macular thickness measurements were taken with spectral-domain optical
coherence tomography. The OPA, a surrogate of pulsatile ocular blood flow, was
measured with the Pascal dynamic contour tonometer. RESULTS: There were no
statistically significant differences between the CABG surgery patients and the
controls with regard to RVC, OPA, peripapillary RNFL thickness and macular
thickness measurements (p>0.05). CONCLUSIONS: CABG surgery does not affect
retinal structures and pulsatile ocular blood flow in the long-term follow-up.
PMID- 25114019
TI - Is it safe to leave an ECMO circuit primed?
AB - Extracorporeal membrane oxygenation (ECMO) is a means of life support for failing
patients who require extreme life-saving measures due to failure of their heart,
lungs or both organs. In a patient suffering cardiac arrest, the faster
circulation via cardiopulmonary resuscitation (CPR) can be instituted the better
the outcome is. If an ECMO circuit needs to be built and primed it may add
significant minutes to the response time. The purpose of this study is to test
for any growth in primed ECMO circuits at given time intervals to prove the
safety of leaving an ECMO circuit primed. This, in turn, may lead to decreased
response time, with an arrest and the placement of the arresting patient on ECMO.
Five ECMO circuits were set up, primed and sampled for bacterial growth at 0, 24,
48 and 72 hours and then at one-week intervals, with an end point of four weeks.
No bacterial growth was found at any point during the sampling process.
PMID- 25114016
TI - Arabidopsis ENHANCED DISEASE SUSCEPTIBILITY1 promotes systemic acquired
resistance via azelaic acid and its precursor 9-oxo nonanoic acid.
AB - Systemic acquired resistance (SAR) is a form of inducible disease resistance that
depends on salicylic acid and its upstream regulator ENHANCED DISEASE
SUSCEPTIBILITY1 (EDS1). Although local Arabidopsis thaliana defence responses
activated by the Pseudomonas syringae effector protein AvrRpm1 are intact in eds1
mutant plants, SAR signal generation is abolished. Here, the SAR-specific
phenotype of the eds1 mutant is utilized to identify metabolites that contribute
to SAR. To this end, SAR bioassay-assisted fractionation of extracts from the
wild type compared with eds1 mutant plants that conditionally express AvrRpm1 was
performed. Using high-performance liquid chromatography followed by mass
spectrometry, systemic immunity was associated with the accumulation of 60
metabolites, including the putative SAR signal azelaic acid (AzA) and its
precursors 9-hydroperoxy octadecadienoic acid (9-HPOD) and 9-oxo nonanoic acid
(ONA). Exogenous ONA induced SAR in systemic untreated leaves when applied at a 4
fold lower concentration than AzA. The data suggest that in planta oxidation of
ONA to AzA might be partially responsible for this response and provide further
evidence that AzA mobilizes Arabidopsis immunity in a concentration-dependent
manner. The AzA fragmentation product pimelic acid did not induce SAR. The
results link the C9 lipid peroxidation products ONA and AzA with systemic rather
than local resistance and suggest that EDS1 directly or indirectly promotes the
accumulation of ONA, AzA, or one or more of their common precursors possibly by
activating one or more pathways that either result in the release of these
compounds from galactolipids or promote lipid peroxidation.
PMID- 25114020
TI - Commentary on: Is it safe to leave an ECMO circuit primed?
PMID- 25114021
TI - One course of adjuvant BEP in clinical stage I nonseminoma mature and expanded
results from the SWENOTECA group.
AB - BACKGROUND: SWENOTECA has since 1998 offered patients with clinical stage I (CS
I) nonseminoma, adjuvant chemotherapy with one course of bleomycin, etoposide and
cisplatin (BEP). The aim has been to reduce the risk of relapse, sparing patients
the need of toxic salvage treatment. Initial results on 312 patients treated with
one course of adjuvant BEP, with a median follow-up of 4.5 years, have been
previously published. We now report mature and expanded results. PATIENTS AND
METHODS: In a prospective, binational, population-based risk-adapted treatment
protocol, 517 Norwegian and Swedish patients with CS I nonseminoma received one
course of adjuvant BEP. Patients with lymphovascular invasion (LVI) in the
primary testicular tumor were recommended one course of adjuvant BEP. Patients
without LVI could choose between surveillance and one course of adjuvant BEP.
Data for patients receiving one course of BEP are presented in this study.
RESULTS: At a median follow-up of 7.9 years, 12 relapses have occurred, all with
IGCCC good prognosis. The latest relapse occurred 3.3 years after adjuvant
treatment. The relapse rate at 5 years was 3.2% for patients with LVI and 1.6%
for patients without LVI. Five-year cause-specific survival was 100%.
CONCLUSIONS: The updated and expanded results confirm a low relapse rate
following one course of adjuvant BEP in CS I nonseminoma. One course of adjuvant
BEP should be considered a standard treatment in CS I nonseminoma with LVI. For
patients with CS I nonseminoma without LVI, one course of adjuvant BEP is also a
treatment option.
PMID- 25114022
TI - Phase II study of stereotactic body radiotherapy to primary tumor and metastatic
locations in oligometastatic nonsmall-cell lung cancer patients.
AB - BACKGROUND: Stereotactic body radiotherapy (SBRT) has emerged as a treatment
modality in patients presenting with oligometastatic nonsmall-cell lung cancer
(NSCLC). SBRT is used as a local consolidative treatment to metastatic disease
sites. The majority of patients included in SBRT trials for oligometastatic NSCLC
have controlled primary tumors and brain metastases. PATIENTS AND METHODS:
Oligometastatic NSCLC patients with <=5 metastatic lesions were included in a
prospective phase II trial to evaluate efficacy and toxicity of SBRT to all
disease sites, primary tumor and metastatic locations. SBRT to a dose of 50 Gy in
10 fractions was delivered. Positron emission tomography-computed tomography (PET
CT) was carried out at baseline and 3 months after SBRT to evaluate the metabolic
response rate according to PET Response Criteria in Solid Tumors (PERCIST). The
progression-free survival (PFS) and overall survival (OS) were calculated using
Kaplan-Meier method from start of chemotherapy or radiotherapy. Side-effects were
scored using the National Cancer Institute Common Terminology Criteria for
Adverse Events (NCI CTCAE) version 3.0. RESULTS: Twenty-six patients received
SBRT after induction chemotherapy (n = 17) or as a primary treatment (n = 9).
Median follow-up was 16.4 months. Overall metabolic response rate was 60% with
seven patients (30%) achieving a complete metabolic remission and 7 (30%) a
partial metabolic response. Any acute grade 2 toxicity was observed in four
patients (15%) and grade 3 pulmonary toxicity in two patients (8%). Median PFS
and OS were 11.2 and 23 months. The 1-year PFS and 1-year OS rate were 45% and
67%, respectively. CONCLUSION: SBRT to all disease sites, primary tumor and
metastatic locations, in oligometastatic NSCLC patients produced an acceptable
median PFS of 11.2 months.
PMID- 25114023
TI - Ion conduction and selectivity in acid-sensing ion channel 1.
AB - The ability of acid-sensing ion channels (ASICs) to discriminate among cations
was assessed based on changes in conductance and reversal potential with ion
substitution. Human ASIC1a was expressed in Xenopus laevis oocytes, and acid
induced currents were measured using two-electrode voltage clamp. Replacement of
extracellular Na(+) with Li(+), K(+), Rb(+), or Cs(+) altered inward conductance
and shifted the reversal potentials consistent with a selectivity sequence of Li
~ Na > K > Rb > Cs. Permeability decreased more rapidly than conductance as a
function of atomic size, with P(K)/P(Na) = 0.1 and G(K)/G(Na) = 0.7 and
P(Rb)/P(Na) = 0.03 and G(Rb)/G(Na) = 0.3. Stimulation of Cl(-) currents when
Na(+) was replaced with Ca(2+), Sr(2+), or Ba(2+) indicated a finite permeability
to divalent cations. Inward conductance increased with extracellular Na(+) in a
hyperbolic manner, consistent with an apparent affinity (K(m)) for Na(+)
conduction of 25 mM. Nitrogen-containing cations, including NH4(+), NH3OH(+), and
guanidinium, were also permeant. In addition to passing through the channels,
guanidinium blocked Na(+) currents, implying competition for a site within the
pore. The role of negative charges in an external vestibule of the pore was
evaluated using the point mutation D434N. The mutant channel had a decreased
single-channel conductance, measured in excised outside-out patches, and a
macroscopic slope conductance that increased with hyperpolarization. It had a
weakened interaction with Na(+) (K(m) = 72 mM) and a selectivity that was shifted
toward larger atomic sizes. We conclude that the selectivity of ASIC1 is based at
least in part on interactions with binding sites both within and internal to the
outer vestibule.
PMID- 25114025
TI - Three-dimensional bioprinting: new horizon for cardiac surgery.
PMID- 25114024
TI - Voltage control of Ca2+ permeation through N-type calcium (Ca(V)2.2) channels.
AB - Voltage-gated calcium (Ca(V)) channels deliver Ca(2+) to trigger cellular
functions ranging from cardiac muscle contraction to neurotransmitter release.
The mechanism by which these channels select for Ca(2+) over other cations is
thought to involve multiple Ca(2+)-binding sites within the pore. Although the
Ca(2+) affinity and cation preference of these sites have been extensively
investigated, the effect of voltage on these sites has not received the same
attention. We used a neuronal preparation enriched for N-type calcium (Ca(V)2.2)
channels to investigate the effect of voltage on Ca(2+) flux. We found that the
EC50 for Ca(2+) permeation increases from 13 mM at 0 mV to 240 mM at 60 mV,
indicating that, during permeation, Ca(2+) ions sense the electric field. These
data were nicely reproduced using a three-binding-site step model. Using
roscovitine to slow Ca(V)2.2 channel deactivation, we extended these measurements
to voltages <0 mV. Permeation was minimally affected at these hyperpolarized
voltages, as was predicted by the model. As an independent test of voltage
effects on permeation, we examined the Ca(2+)-Ba(2+) anomalous mole fraction (MF)
effect, which was both concentration and voltage dependent. However, the Ca(2+)
Ba(2+) anomalous MF data could not be reproduced unless we added a fourth site to
our model. Thus, Ca(2+) permeation through Ca(V)2.2 channels may require at least
four Ca(2+)-binding sites. Finally, our results suggest that the high affinity of
Ca(2+) for the channel helps to enhance Ca(2+) influx at depolarized voltages
relative to other ions (e.g., Ba(2+) or Na(+)), whereas the absence of voltage
effects at negative potentials prevents Ca(2+) from becoming a channel blocker.
Both effects are needed to maximize Ca(2+) influx over the voltages spanned by
action potentials.
PMID- 25114026
TI - Positive psychological states and health behaviors in acute coronary syndrome
patients: A qualitative study.
AB - Positive psychological states are linked to superior cardiac outcomes, possibly
mediated through increased participation in health behaviors. Trained study staff
conducted in-depth semi-structured interviews in the hospital and 3 months later
for 34 patients diagnosed with an acute coronary syndrome. These interviews
focused on positive psychological states, cardiac health behaviors, and their
connection; the interviews were transcribed and independently coded using
directed content analysis. Both optimism and positive affect were associated with
completion of physical activity and healthy eating in a bidirectional manner. In
contrast, gratitude, while common, was infrequently linked to completion of
health behaviors.
PMID- 25114028
TI - Mode of swine hepatitis E virus infection and replication in primary human
hepatocytes.
AB - The aim of this study was to investigate the infection and replication of swine
derived hepatitis E virus (HEV) in primary cultured human hepatocytes (PHCs).
Hepatocytes were cultured from the resected normal livers of patients with
metastatic tumours. These cultured hepatocytes were infected with swine-derived
genotype 3 or 4 HEV. Viral replication was monitored using reverse transcriptase
quantitative PCR. The amount of HEV RNA increased in the culture media and cells
following infection. Immunofluorescence staining implied that the spread of HEV
infection in hepatocytes was attributed mainly to cell-to-cell transmission via
the cell membrane. The sequences of the inoculated and propagated HEV were
determined to examine whether sequence variation occurred during infection.
Sequence analysis showed that there were no differences between inoculated and
propagated HEV, demonstrating that in vitro infection and replication of swine
HEV in PHCs occurred without sequence variation.
PMID- 25114030
TI - MitraClip procedure for the treatment of a pseudo-cleft in the posterior mitral
leaflet.
PMID- 25114029
TI - Identification and functional analysis of inter-subunit disulfide bonds of the F
protein of Helicoverpa armigera nucleopolyhedrovirus.
AB - The major envelope fusion protein F of the budded virus of baculoviruses consists
of two disulfide-linked subunits: an N-terminal F2 subunit and a C-terminal,
membrane-anchored F1 subunit. There is one cysteine in F2 and there are 15
cysteines in F1, but their role in disulfide linking is largely unknown. In this
study, the inter- and intra-subunit disulfide bonds of the Helicoverpa armigera
single nucleocapsid nucleopolyhedrovirus (HearNPV) F protein were analysed by
site-directed mutagenesis. Results indicated that in a functional F protein, an
inter-subunit disulfide bond exists between amino acids C108 (F2) and C241 (F1).
When C241 was mutated, an alternative disulfide bond was formed between C108 and
C232, rendering F non-functional. No inter-subunit bridge was observed in a
double C232/C241 mutant of F1. C403 was not involved in the formation of inter
subunit disulfide bonding, but mutation of this amino acid decreased viral
infectivity significantly, suggesting that it might be involved in intra-subunit
disulfide bonds. The influence of reductant [tris(2-carboxyethyl) phosphine
(TCEP)] and free-thiol inhibitors [4-acetamido-4'-maleimidylstilbene 2,2'
disulfonic acid (AMS) and 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB)] on the
infectivity of HearNPV was tested. The results indicated that TCEP greatly
decreased the infection of HzAm1 cells by HearNPV. In contrast, AMS and DTNB had
no inhibitory effect on viral infectivity. The data suggested that free
thiol/disulfide isomerization was not likely to play a role in viral entry and
infectivity.
PMID- 25114027
TI - Translating advances in cardiogenetics into effective clinical practice.
AB - In this article we describe a qualitative research study in which we explored
individuals' subjective experiences of both genetic testing and cardiogenetic
disorders. Using a grounded theory approach, we coded and analyzed interview and
focus group transcripts from 50 participants. We found that just under half of
the participants who received their diagnosis during the study reported
difficulty understanding information about both the purpose of genetic testing
and their cardiac disease. A high level of anxiety about genetic testing and
cardiac symptoms exacerbated individuals' cognitive confusion. Participants
reported both positive and negative interactions with the medical community,
depending on health care professionals' knowledge of cardiogenetic disorders.
Overall, participants expressed a range of attitudes--positive, negative, and
ambivalent--toward genetic testing. We conclude with a discussion of the barriers
to achieving effective clinical care for genetic conditions and offer suggestions
for improving collaborative decision making between physicians and patients.
PMID- 25114031
TI - Emerging epidemic of hepatitis C virus infections among young nonurban persons
who inject drugs in the United States, 2006-2012.
AB - BACKGROUND: Reports of acute hepatitis C in young persons in the United States
have increased. We examined data from national surveillance and supplemental case
follow-up at selected jurisdictions to describe the US epidemiology of hepatitis
C virus (HCV) infection among young persons (aged <=30 years). METHODS: We
examined trends in incidence of acute hepatitis C among young persons reported to
the Centers for Disease Control and Prevention (CDC) during 2006-2012 by state,
county, and urbanicity. Sociodemographic and behavioral characteristics of HCV
infected young persons newly reported from 2011 to 2012 were analyzed from case
interviews and provider follow-up at 6 jurisdictions. RESULTS: From 2006 to 2012,
reported incidence of acute hepatitis C increased significantly in young persons
13% annually in nonurban counties (P = .003) vs 5% annually in urban counties (P
= .028). Thirty (88%) of 34 reporting states observed higher incidence in 2012
than 2006, most noticeably in nonurban counties east of the Mississippi River. Of
1202 newly reported HCV-infected young persons, 52% were female and 85% were
white. In 635 interviews, 75% of respondents reported injection drug use. Of
respondents reporting drug use, 75% had abused prescription opioids, with first
use on average 2.0 years before heroin. CONCLUSIONS: These data indicate an
emerging US epidemic of HCV infection among young nonurban persons of
predominantly white race. Reported incidence was higher in 2012 than 2006 in at
least 30 states, with largest increases in nonurban counties east of the
Mississippi River. Prescription opioid abuse at an early age was commonly
reported and should be a focus for medical and public health intervention.
PMID- 25114033
TI - Editorial commentary: protease inhibitor monotherapy: safe for the CNS in durably
suppressed patients?
PMID- 25114034
TI - Immunogenic cell death inducers as anticancer agents.
PMID- 25114036
TI - Ras in epidermal proliferation.
PMID- 25114032
TI - A prospective cohort study of neurocognitive function in aviremic HIV-infected
patients treated with 1 or 3 antiretrovirals.
AB - BACKGROUND: The evolution of neurocognitive performance in aviremic human
immunodeficiency virus (HIV)-positive patients treated with <3 antiretrovirals is
unknown. METHODS: We prospectively included aviremic (>=1 year) HIV-positive
patients, without concomitant major neurocognitive confounders, currently
receiving boosted lopinavir or darunavir as monotherapy (n = 67) or triple
antiretroviral therapy (ART) (n = 67) for >=1 year. We evaluated neurocognitive
function (7 domains) at baseline and after 1 year. We performed analysis of
covariance to evaluate if 1 additional year of exposure to monotherapy compared
with triple ART had an effect on Global Deficit Score (GDS) changes after
adjustment for potential confounders. We also compared the evolution of
neurocognitive performance and impairment rates. RESULTS: Intention-to-treat
analysis showed that monotherapy did not influence 1-year GDS change after
adjustment for significant confounders (age, ethnicity, duration of therapy,
hepatitis C virus status, and HOMA-IR index); the adjusted effect was -0.04 (95%
confidence interval, -.14 to .05; P = .38). Neurocognitive stability was observed
with monotherapy and triple therapy (GDS crude mean change, -0.09 [95% confidence
interval, -.16 to -.01] vs -0.08 [-.14 to -.02]), after 1 year of follow-up,
similar proportions of patients changed neurocognitive status from impaired to
unimpaired (monotherapy, 4 of 18 [22.2%]; triple therapy, 4 of 19 [21.1%]; P =
.91) and vice versa (monotherapy, 5 of 44 [10.2%] and triple therapy, 3 of 45
[6.3%]; P = .48). Similar results were observed in an on-treatment analysis and
with use of clinical ratings instead of GDS changes. CONCLUSIONS: The number of
antiretrovirals included in the ART regimen does not seem to influence the
evolution of neurocognitive function in HIV-infected patients with suppressed
plasma viremia.
PMID- 25114037
TI - Knowledge-based computational models.
PMID- 25114035
TI - Targeting lemurs against cancer metastasis.
PMID- 25114039
TI - Caspase-2 regulates oncogene-induced senescence.
AB - Cellular senescence is activated by numerous cellular insults, in particular
those driving cancer formation, resulting in stable proliferation arrest and
acquisition of specific features. By self-opposing to oncogenic stimulation,
senescence is considered as a failsafe program, allowing, when functional, to
inhibit cancers occurrence. Compelling evidences suggest a tumor suppressive
activity of caspase-2, eventually independently of its effect on cell death. The
original results described here demonstrate that this tumor suppressive activity
of caspase-2 is mediated, at least in part, by its pro-senescing activity.
Indeed, we have demonstrated in vitro and in vivo that loss of function of
caspase-2 allows to escape oncogenic stress induced senescence. These results are
discussed in the context of known tumor suppressive activity of caspase-2.
PMID- 25114040
TI - Development of a real-time PCR for the detection of pathogenic Leptospira spp. in
California sea lions.
AB - Several real-time PCR assays are currently used for detection of pathogenic
Leptospira spp.; however, few methods have been described for the successful
evaluation of clinical urine samples. This study reports a rapid assay for the
detection of pathogenic Leptospira spp. in California sea lions Zalophus
californianus using real-time PCR with primers and a probe targeting the lipL32
gene. The PCR assay had high analytic sensitivity-the limit of detection was 3
genome copies per PCR volume using L. interrogans serovar Pomona DNA and 100%
analytic specificity; it detected all pathogenic leptospiral serovars tested and
none of the non-pathogenic Leptospira species (L. biflexa and L. meyeri serovar
Semaranga), the intermediate species L. inadai, or the non-Leptospira pathogens
tested. Our assay had an amplification efficiency of 1.00. Comparisons between
the real-time PCR assay and culture isolation for detection of pathogenic
Leptospira spp. in urine and kidney tissue samples from California sea lions
showed that samples were more often positive by real-time PCR than by culture
methods. Inclusion of an internal amplification control in the real-time PCR
assay showed no inhibitory effects in PCR negative samples. These studies
indicated that our real-time PCR assay has high analytic sensitivity and
specificity for the rapid detection of pathogenic Leptospira species in urine and
kidney tissue samples.
PMID- 25114038
TI - Tumor suppressor p53 negatively regulates glycolysis stimulated by hypoxia
through its target RRAD.
AB - Cancer cells display enhanced glycolysis to meet their energetic and biosynthetic
demands even under normal oxygen concentrations. Recent studies have revealed
that tumor suppressor p53 represses glycolysis under normoxia as a novel
mechanism for tumor suppression. As a common microenvironmental stress for
tumors, hypoxia drives the metabolic switch from the oxidative phosphorylation to
glycolysis, which is crucial for survival and proliferation of cancer cells under
hypoxia. The p53's role and mechanism in regulating glycolysis under hypoxia is
poorly understood. Here, we found that p53 represses hypoxia-stimulated
glycolysis in cancer cells through RRAD, a newly-identified p53 target. RRAD
expression is frequently decreased in lung cancer. Ectopic expression of RRAD
greatly reduces glycolysis whereas knockdown of RRAD promotes glycolysis in lung
cancer cells. Furthermore, RRAD represses glycolysis mainly through inhibition of
GLUT1 translocation to the plasma membrane. Under hypoxic conditions, p53 induces
RRAD, which in turn inhibits the translocation of GLUT1 and represses glycolysis
in lung cancer cells. Blocking RRAD by siRNA greatly abolishes p53's function in
repressing glycolysis under hypoxia. Taken together, our results revealed an
important role and mechanism of p53 in antagonizing the stimulating effect of
hypoxia on glycolysis, which contributes to p53's function in tumor suppression.
PMID- 25114041
TI - Benign effect of the fish parasitic isopod Ceratothoa cf. imbricata on Selenotoca
multifasciata (Scatophagidae) from Australia.
AB - The tongue-biter cymothoid isopod Ceratothoa cf. imbricata is nearly ubiquitous
in buccal cavities of the banded scat Selenotoca multifasciata (Scatophagidae)
from Waterloo Bay, south-east Queensland. To test whether infestation affects
fish growth or condition significantly, we explored parasitism and condition in
122 S. multifasciata specimens. The internal area of the buccal cavity and that
occupied by ovigerous female isopods were measured, allowing the relative
proportion of free internal area of the buccal cavity (PFIAO) to be calculated.
Of 122 fish, 119 (97.5%) were infected; 35.3% had large female isopods, the
remaining infections comprised much smaller mancae, juveniles and adult males.
Mean intensity of infection was significantly correlated with fish total length
(TL). In some fish, the female isopod occupied up to 80% of the buccal cavity
area. There was little evidence of attachment damage in the buccal cavity; only 9
of 43 hosts analysed had restricted damage to the tissues at the points of
attachment of the female isopod. Condition factor, food intensity index and
stomach weight did not differ between fish with and without female C. cf.
imbricata. The relative proportion of free internal area of the buccal cavity
with respect to the fish total length (PFIAO/TL2 ratio) of fish infected with
females correlated with food intensity and condition factor. Although the
correlation was significant, the actual effect was not large because more than
70% of these 2 indices was not explained by the PFIAO/TL2 ratio (r2 < 0.3 in both
cases). Despite the dramatic appearance of infestations and the high prevalence
of C. cf. imbricata in the population, the near-absence of pathological
alterations and the limited effect of the isopod on the condition indices and
food intensity suggest that this isopod is relatively benign for S.
multifasciata.
PMID- 25114042
TI - Identification and analysis of three virulence-associated TonB-dependent outer
membrane receptors of Pseudomonas fluorescens.
AB - Pseudomonas fluorescens is a Gram-negative bacterium that can infect a wide range
of farmed fish. However, very little is known about the virulence mechanism of P.
fluorescens as a fish pathogen. In this study, we identified and analyzed 3 TonB
dependent outer membrane receptors (TDRs) from a pathogenic P. fluorescens strain
isolated from fish. In silico analysis revealed that all 3 proteins (named Tdr1
to 3) possess structural domains typical of TDRs. Quantitative real time RT-PCR
analysis showed that tdr1, tdr2, and tdr3 expressions were upregulated under iron
depleted conditions. Compared to the wild type, mutants defective in tdr1, tdr2,
and tdr3 were retarded in growth to different extents. Infection in a turbot
Scophthalmus maximus model showed that all 3 mutants were impaired in their
ability to desseminate into and colonize host tissues. In addition, the tdr1 and
tdr3 mutants exhibited significantly reduced virulence. When used as subunit
vaccines, purified recombinant proteins of Tdr1, Tdr2, and, in particular, Tdr3
elicited significant protection in turbot against lethal P. fluorescens
challenge. The vaccinated fish produced specific serum antibodies, which, when
incubated with P. fluorescens, blocked infection of P. fluorescens in fish cells.
Together these results indicate that Tdr1, Tdr2, and Tdr3 are iron-regulated
factors that participate in bacterial virulence and induce protective immunity as
subunit vaccines.
PMID- 25114043
TI - Effects of experimentally induced infections of goldfish Carassius auratus with
cyprinid herpesvirus 2 (CyHV-2) at various water temperatures.
AB - In this study, we examined the influence of water temperature on the development
of herpesviral haematopoietic necrosis (HVHN) in goldfish Carassius auratus after
experimentally induced infection with cyprinid herpesvirus 2 (CyHV-2). In Expt 1,
Ryukin goldfish were infected with CyHV-2 by intraperitoneal injection and
maintained at 4 different water temperatures. Cumulative mortalities of the 15,
20, 25 and 30 degrees C groups were 10, 90, 90 and 60%, respectively. Therefore,
the temperature range of 20-25 degrees C is considered highly permissive for
HVHN. One of 6 surviving fish of the 15 degrees C group died after a rapid
temperature increase to 25 degrees C at 30 d post infection. All 3 Edonishiki
goldfish, co-reared with the surviving Ryukin in tanks where the water
temperature was increased from 15 to 25 degrees C, died. In Expt 2, Edonishiki
goldfish were exposed to CyHV-2 by bath immersion at 13 or 24 degrees C,
resulting in cumulative mortalities of 0 and 87%, respectively, at 28 d post
exposure. No mortality of the surviving Edonishiki in the 13 degrees C treatment
was observed when the water temperature was increased to 24 degrees C. In
addition, in Expt 2, no mortality was observed in any Ranchu co-reared with CyHV
2-immersed Edonishiki in the group where water temperature was increased from 13
to 24 degrees C, even after re-immersion challenge with CyHV-2. It is interesting
to note that CyHV-2 DNA was detected in the kidneys of 4 of the 5 surviving
Ranchu co-reared with the CyHV-2-immersed Edonishiki group where the water
temperature was increased from 13 to 24 degrees C. Therefore, it is likely that
the surviving Edonishiki of the 13 degrees C group were virus carriers. This
study indicates that most fish infected with CyHV-2 at 13-15 degrees C acquire
resistance to HVHN, but as carriers they are able to infect naive fish.
PMID- 25114044
TI - Rearing practices identified as risk factors for ostreid herpesvirus 1 (OsHV-1)
infection in Pacific oyster Crassostrea gigas spat.
AB - Early detection of Pacific oyster spat infected with ostreid herpesvirus 1 (OsHV
1) could prevent introduction of OsHV-1-infected individuals into farming areas
or onshore rearing facilities, thus reducing the risk of infection of naive
oysters in such production systems. Experiments were conducted on several hundred
oyster spat provided by producers in order to examine whether early rearing
practices could be considered as potential risk factors for (1) OsHV-1 infection
as detected by molecular methods and (2) spat mortality experimentally induced
through thermal challenge. Spat groups collected on oyster beds and hatchery spat
reared in growout areas during summer exhibited higher viral DNA contamination
and mortalities during the trial than spat kept in onshore rearing facilities.
Quantification of viral DNA before and during the trial showed that infection
prevalence and intensity changed over time and revealed latent infection
initially unsuspected in 3 of 10 groups. Thermal challenge induced a clear
increase in the probability of detecting infected individuals, particularly for
groups exhibiting significant prevalence of OsHV-1-contaminated spat prior to the
challenge. The use of detection methods are discussed in relation to early
rearing practices and disease control strategies.
PMID- 25114045
TI - Ameson metacarcini sp. nov. (Microsporidia) infecting the muscles of Dungeness
crabs Metacarcinus magister from British Columbia, Canada.
AB - The Dungeness crab Metacarcinus magister supports a large and valuable fishery
along the west coast of North America. Since 1998, Dungeness crabs exhibiting
pink- to orange-colored joints and opaque white musculature have been
sporadically observed in low prevalence from the Fraser River delta of British
Columbia, Canada. We provide histological, ultrastructural, and molecular
evidence that this condition is caused by a new microsporidian parasite. Crabs
displaying gross symptoms were confirmed to have heavy infections of ovoid-shaped
microsporidian spores (~1.8 * 1.4 um in size) within muscle bundles of the
skeletal musculature. The parasite apparently infected the outer periphery of
each muscle bundle, and then proliferated into the muscle fibres near the centre
of each infected bundle. Light infections were observed in heart tissues, and
occasionally spores were observed within the fixed phagocytes lining the blood
vessels of the hepatopancreas. Transmission electron microscopy (TEM) revealed
multiple life stages of a monokaryotic microsporidian parasite within the
sarcoplasm of muscle fibres. Molecular analysis of partial small subunit rRNA
sequence data from the new species revealed an affinity to Ameson, a genus of
Microsporidia infecting marine crustaceans. Based on morphological and molecular
data, the new species is distinct from Nadelspora canceri, a related
microsporidian that also infects the muscles of this host. At present, little is
known about the distribution, seasonality, and transmission of A. metacarcini in
M. magister.
PMID- 25114046
TI - Variation in black and white band disease progression in corals of the Gulf of
Mannar and Palk Bay, Southeastern India.
AB - Information on the progression of coral diseases and transmission to live corals
is scarce despite the fact that coral disease poses one of the most lethal
threats to the survival of coral reefs. In this study, in situ progression rates
of lesions similar to black band disease (BBD) and white band disease (WBD) were
measured in different species of corals from the Gulf of Mannar (GoM) and Palk
Bay, southeastern India, during the period between January and December of 2009.
Maximum progression rates of 3 and 1.6 cm mo-1 for BBD and WBD, respectively,
were observed during May, when the temperature exceeded 30 degrees C. The annual
progression rate was 10.9 and 4.9 cm yr-1 for BBD at GoM and Palk Bay,
respectively. Significant variation in the progression rate (p < 0.001) was
observed between months in all the examined species. Significant correlation
between temperature and disease progression rates for BBD (R2 = 0.875, p <=
0.001) and WBD (R2 = 0.776, p <= 0.001) was recorded. Rates of disease
progression were higher in Palk Bay than in GoM. This could be attributed to the
higher temperature coupled with higher anthropogenic activities in Palk Bay.
Severe mortality was observed due to both BBD and WBD. No sign of recovery was
noticed in the disease-affected colonies at either study site. Anthropogenic
activities should be checked, and further research on both the transmission and
progression rate and role of the diseases in reef dynamics should be carried out
to understand the causal factors in reef degradation and generate a plan to
manage the reef properly.
PMID- 25114047
TI - Detection of the emerging amphibian pathogens Batrachochytrium dendrobatidis and
ranavirus in Russia.
AB - In a population of the European common toad Bufo bufo from a rural pond in the
region of Lake Glubokoe Regional Reserve in Moscow province, Russia, unexplained
mass mortality events involving larvae and metamorphs have been observed over a
monitoring period of >20 yr. We tested toads from this and a nearby site for the
emerging amphibian pathogens Batrachochytrium dendrobatidis (Bd) and ranavirus
(Rv). Both pathogens were detected, and at the rural pond site, with the above
noted losses and decline in toad breeding success, 40% of B. bufo metamorphs were
Bd positive, 46% were Rv positive and 20% were co-infected with both pathogens.
Toad metamorphs from a neighbouring water body were also Bd and Rv positive (25
and 55%, respectively). This is the first confirmation of these pathogens in
Russia. Questions remain as to the origins of these pathogens in Russia and their
roles in documented mass mortality events.
PMID- 25114048
TI - Rrd1p, an RNA polymerase II-specific prolyl isomerase and activator of
phosphoprotein phosphatase, promotes transcription independently of rapamycin
response.
AB - Rrd1p (resistance to rapamycin deletion 1) has been previously implicated in
controlling transcription of rapamycin-regulated genes in response to rapamycin
treatment. Intriguingly, we show here that Rrd1p associates with the coding
sequence of a galactose-inducible and rapamycin non-responsive GAL1 gene, and
promotes the association of RNA polymerase II with GAL1 in the absence of
rapamycin treatment following transcriptional induction. Consistently,
nucleosomal disassembly at GAL1 is impaired in the absence of Rrd1p, and GAL1
transcription is reduced in the Deltarrd1 strain. Likewise, Rrd1p associates with
the coding sequences of other rapamycin non-responsive and inducible GAL genes to
promote their transcription in the absence of rapamycin treatment. Similarly,
inducible, but rapamycin-responsive, non-GAL genes such as CTT1, STL1 and CUP1
are also regulated by Rrd1p. However, transcription of these inducible GAL and
non-GAL genes is not altered in the absence of Rrd1p when the steady-state is
reached after long transcriptional induction. Consistently, transcription of the
constitutively active genes is not changed in the Deltarrd1 strain. Taken
together, our results demonstrate a new function of Rrd1p in stimulation of
initial rounds of transcription, but not steady-state/constitutive transcription,
of both rapamycin-responsive and non-responsive genes independently of rapamycin
treatment.
PMID- 25114049
TI - Structure and function of TatD exonuclease in DNA repair.
AB - TatD is an evolutionarily conserved protein with thousands of homologues in all
kingdoms of life. It has been suggested that TatD participates in DNA
fragmentation during apoptosis in eukaryotic cells. However, the cellular
functions and biochemical properties of TatD in bacterial and non-apoptotic
eukaryotic cells remain elusive. Here we show that Escherichia coli TatD is a
Mg(2+)-dependent 3'-5' exonuclease that prefers to digest single-stranded DNA and
RNA. TatD-knockout cells are less resistant to the DNA damaging agent hydrogen
peroxide, and TatD can remove damaged deaminated nucleotides from a DNA chain,
suggesting that it may play a role in the H2O2-induced DNA repair. The crystal
structure of the apo-form TatD and TatD bound to a single-stranded three
nucleotide DNA was determined by X-ray diffraction methods at a resolution of 2.0
and 2.9 A, respectively. TatD has a TIM-barrel fold and the single-stranded DNA
is bound at the loop region on the top of the barrel. Mutational studies further
identify important conserved metal ion-binding and catalytic residues in the TatD
active site for DNA hydrolysis. We thus conclude that TatD is a new class of TIM
barrel 3'-5' exonuclease that not only degrades chromosomal DNA during apoptosis
but also processes single-stranded DNA during DNA repair.
PMID- 25114050
TI - Hydration of protein-RNA recognition sites.
AB - We investigate the role of water molecules in 89 protein-RNA complexes taken from
the Protein Data Bank. Those with tRNA and single-stranded RNA are less hydrated
than with duplex or ribosomal proteins. Protein-RNA interfaces are hydrated less
than protein-DNA interfaces, but more than protein-protein interfaces. Majority
of the waters at protein-RNA interfaces makes multiple H-bonds; however, a
fraction do not make any. Those making H-bonds have preferences for the polar
groups of RNA than its partner protein. The spatial distribution of waters makes
interfaces with ribosomal proteins and single-stranded RNA relatively 'dry' than
interfaces with tRNA and duplex RNA. In contrast to protein-DNA interfaces,
mainly due to the presence of the 2'OH, the ribose in protein-RNA interfaces is
hydrated more than the phosphate or the bases. The minor groove in protein-RNA
interfaces is hydrated more than the major groove, while in protein-DNA
interfaces it is reverse. The strands make the highest number of water-mediated H
bonds per unit interface area followed by the helices and the non-regular
structures. The preserved waters at protein-RNA interfaces make higher number of
H-bonds than the other waters. Preserved waters contribute toward the affinity in
protein-RNA recognition and should be carefully treated while engineering protein
RNA interfaces.
PMID- 25114051
TI - Molecular basis for the differential interaction of plant mitochondrial VDAC
proteins with tRNAs.
AB - In plants, the voltage-dependent anion-selective channel (VDAC) is a major
component of a pathway involved in transfer RNA (tRNA) translocation through the
mitochondrial outer membrane. However, the way in which VDAC proteins interact
with tRNAs is still unknown. Potato mitochondria contain two major mitochondrial
VDAC proteins, VDAC34 and VDAC36. These two proteins, composed of a N-terminal
alpha-helix and of 19 beta-strands forming a beta-barrel structure, share 75%
sequence identity. Here, using both northwestern and gel shift experiments, we
report that these two proteins interact differentially with nucleic acids. VDAC34
binds more efficiently with tRNAs or other nucleic acids than VDAC36. To further
identify specific features and critical amino acids required for tRNA binding, 21
VDAC34 mutants were constructed and analyzed by northwestern. This allowed us to
show that the beta-barrel structure of VDAC34 and the first 50 amino acids that
contain the alpha-helix are essential for RNA binding. Altogether the work shows
that during evolution, plant mitochondrial VDAC proteins have diverged so as to
interact differentially with nucleic acids, and this may reflect their
involvement in various specialized biological functions.
PMID- 25114052
TI - Quantitative models for accelerated protein dissociation from nucleosomal DNA.
AB - Binding of transcription factors to their binding sites in promoter regions is
the fundamental event in transcriptional gene regulation. When a transcription
factor binding site is located within a nucleosome, the DNA has to partially
unwrap from the nucleosome to allow transcription factor binding. This reduces
the rate of transcription factor binding and is a known mechanism for regulation
of gene expression via chromatin structure. Recently a second mechanism has been
reported where transcription factor off-rates are dramatically increased when
binding to target sites within the nucleosome. There are two possible
explanations for such an increase in off-rate short of an active role of the
nucleosome in pushing the transcription factor off the DNA: (i) for dimeric
transcription factors the nucleosome can change the equilibrium between monomeric
and dimeric binding or (ii) the nucleosome can change the equilibrium between
specific and non-specific binding to the DNA. We explicitly model both scenarios
and find that dimeric binding can explain a large increase in off-rate while the
non-specific binding model cannot be reconciled with the large, experimentally
observed increase. Our results suggest a general mechanism how nucleosomes
increase transcription factor dissociation to promote exchange of transcription
factors and regulate gene expression.
PMID- 25114053
TI - Eukaryotic translation initiation factor eIF5 promotes the accuracy of start
codon recognition by regulating Pi release and conformational transitions of the
preinitiation complex.
AB - eIF5 is the GTPase activating protein (GAP) for the eIF2 . GTP . Met-tRNAi (Met)
ternary complex with a critical role in initiation codon selection. Previous work
suggested that the eIF5 mutation G31R/SUI5 elevates initiation at UUG codons by
increasing GAP function. Subsequent work implicated eIF5 in rearrangement of the
preinitiation complex (PIC) from an open, scanning conformation to a closed state
at AUG codons, from which Pi is released from eIF2 . GDP . Pi. To identify eIF5
functions crucial for accurate initiation, we investigated the consequences of
G31R on GTP hydrolysis and Pi release, and the effects of intragenic G31R
suppressors on these reactions, and on the partitioning of PICs between open and
closed states. eIF5-G31R altered regulation of Pi release, accelerating it at UUG
while decreasing it at AUG codons, consistent with its ability to stabilize the
closed complex at UUG. Suppressor G62S mitigates both defects of G31R, accounting
for its efficient suppression of UUG initiation in G31R,G62S cells; however
suppressor M18V impairs GTP hydrolysis with little effect on PIC conformation.
The strong defect in GTP hydrolysis conferred by M18V likely explains its broad
suppression of Sui(-) mutations in numerous factors. We conclude that both of
eIF5's functions, regulating Pi release and stabilizing the closed PIC
conformation, contribute to stringent AUG selection in vivo.
PMID- 25114054
TI - A statistical model of ChIA-PET data for accurate detection of chromatin 3D
interactions.
AB - Identification of three-dimensional (3D) interactions between regulatory elements
across the genome is crucial to unravel the complex regulatory machinery that
orchestrates proliferation and differentiation of cells. ChIA-PET is a novel
method to identify such interactions, where physical contacts between regions
bound by a specific protein are quantified using next-generation sequencing.
However, determining the significance of the observed interaction frequencies in
such datasets is challenging, and few methods have been proposed. Despite the
fact that regions that are close in linear genomic distance have a much higher
tendency to interact by chance, no methods to date are capable of taking such
dependency into account. Here, we propose a statistical model taking into account
the genomic distance relationship, as well as the general propensity of anchors
to be involved in contacts overall. Using both real and simulated data, we show
that the previously proposed statistical test, based on Fisher's exact test,
leads to invalid results when data are dependent on genomic distance. We also
evaluate our method on previously validated cell-line specific and constitutive
3D interactions, and show that relevant interactions are significant, while
avoiding over-estimating the significance of short nearby interactions.
PMID- 25114055
TI - A combination of computational and experimental approaches identifies DNA
sequence constraints associated with target site binding specificity of the
transcription factor CSL.
AB - Regulation of transcription is fundamental to development and physiology, and
occurs through binding of transcription factors to specific DNA sequences in the
genome. CSL (CBF1/Suppressor of Hairless/LAG-1), a core component of the Notch
signaling pathway, is one such transcription factor that acts in concert with co
activators or co-repressors to control the activity of associated target genes.
One fundamental question is how CSL can recognize and select among different DNA
sequences available in vivo and whether variations between selected sequences can
influence its function. We have therefore investigated CSL-DNA recognition using
computational approaches to analyze the energetics of CSL bound to different DNAs
and tested the in silico predictions with in vitro and in vivo assays. Our
results reveal novel aspects of CSL binding that may help explain the range of
binding observed in vivo. In addition, using molecular dynamics simulations, we
show that domain-domain correlations within CSL differ significantly depending on
the DNA sequence bound, suggesting that different DNA sequences may directly
influence CSL function. Taken together, our results, based on computational
chemistry approaches, provide valuable insights into transcription factor-DNA
binding, in this particular case increasing our understanding of CSL-DNA
interactions and how these may impact on its transcriptional control.
PMID- 25114056
TI - Characterizing RNA ensembles from NMR data with kinematic models.
AB - Functional mechanisms of biomolecules often manifest themselves precisely in
transient conformational substates. Researchers have long sought to structurally
characterize dynamic processes in non-coding RNA, combining experimental data
with computer algorithms. However, adequate exploration of conformational space
for these highly dynamic molecules, starting from static crystal structures,
remains challenging. Here, we report a new conformational sampling procedure,
KGSrna, which can efficiently probe the native ensemble of RNA molecules in
solution. We found that KGSrna ensembles accurately represent the conformational
landscapes of 3D RNA encoded by NMR proton chemical shifts. KGSrna resolves
motionally averaged NMR data into structural contributions; when coupled with
residual dipolar coupling data, a KGSrna ensemble revealed a previously
uncharacterized transient excited state of the HIV-1 trans-activation response
element stem-loop. Ensemble-based interpretations of averaged data can aid in
formulating and testing dynamic, motion-based hypotheses of functional mechanisms
in RNAs with broad implications for RNA engineering and therapeutic intervention.
PMID- 25114058
TI - Can we improve the performance and reporting of investigator-initiated clinical
trials? Rheumatoid arthritis as an example.
AB - Investigator-initiated trials, some of which have been referred to as comparative
effectiveness trials, pragmatic trials, or strategy trials, are sometimes
considered to be of greater clinical importance than industry-driven trials,
because they address important but unresolved clinical questions that differ from
the questions asked in industry-driven trials. Regulatory authorities have
provided methodological guidance for industry-driven trials for the approval of
new treatments, but such guidance is less clear for investigator-initiated
trials. The European League Against Rheumatism (EULAR) task force for the update
of the recommendations for the management of rheumatoid arthritis has critically
looked at the methodological quality and conduct of many investigator-initiated
trials, and has identified a number of concerns. In this Viewpoint paper, we
highlight commonly encountered issues that are discussed using examples of well
known investigator-initiated trials. These issues cover three themes: (1) design
choice (superiority vs non-inferiority designs); (2) statistical power and (3)
convenience reporting. Since we acknowledge the importance of investigator
initiated research, we also propose a shortlist of points-to-consider when
designing, performing and reporting investigator-initiated trials.
PMID- 25114059
TI - Estimation of heritability of different outcomes for genetic studies of TNFi
response in patients with rheumatoid arthritis.
AB - OBJECTIVES: Pharmacogenetic studies of tumour necrosis factor inhibitors (TNFi)
response in patients with rheumatoid arthritis (RA) have largely relied on the
changes in complex disease scores, such as disease activity score 28 (DAS28), as
a measure of treatment response. It is expected that genetic architecture of such
complex score is heterogeneous and not very suitable for pharmacogenetic studies.
We aimed to select the most optimal phenotype for TNFi response using
heritability estimates. METHODS: Using two linear mixed-modelling approaches
(Bayz and GCTA), we estimated heritability, together with genomic and
environmental correlations for the TNFi drug-response phenotype DeltaDAS28 and
its separate components: Delta swollen joint count (SJC), Delta tender joint
count (TJC), Delta erythrocyte sedimentation rate (ESR) and Delta visual-analogue
scale of general health (VAS-GH). For this, we used genome-wide single nucleotide
polymorphism (SNP) data from 878 TNFi-treated Dutch patients with RA.
Furthermore, a multivariate genome-wide association study (GWAS) approach was
implemented, analysing separate DAS28 components simultaneously. RESULTS: The
highest heritability estimates were found for DeltaSJC (h(2)gbayz=0.76 and
h(2)gGCTA=0.87) and DeltaTJC (h(2)gbayz=0.62 and h(2)gGCTA=0.82); lower
heritability was found for DeltaDAS28 (h(2)gbayz=0.59 and h(2)gGCTA=0.71) while
estimates for DeltaESR and DeltaVASGH were near or equal to zero. The highest
genomic correlations were observed for DeltaSJC and DeltaTJC (0.49), and the
highest environmental correlation was seen between DeltaTJC and DeltaVASGH
(0.62). The multivariate GWAS did not generate excess of low p values as compared
with a univariate analysis of DeltaDAS28. CONCLUSIONS: Our results indicate that
multiple SNPs together explain a substantial portion of the variation in change
in joint counts in TNFi-treated patients with RA. In conclusion, of the outcomes
studied, the joint counts are most suitable for TNFi pharmacogenetics in RA.
PMID- 25114061
TI - Development of a patient-reported outcome measure of tophus burden: the Tophus
Impact Questionnaire (TIQ-20).
AB - BACKGROUND: Tophus burden is currently measured using physical examination and
imaging methods. The aim of this study was to develop a patient-reported outcome
(PRO) tool to assess tophus burden in people with gout. METHODS: The responses
from interviews with 25 people with tophaceous gout were used to generate items
for a preliminary PRO tool. Following cognitive testing of each item, a
preliminary 34-item questionnaire was administered to 103 people with tophaceous
gout. Rasch analysis generated a 20-item Tophus Impact Questionnaire (TIQ-20).
Test-retest reproducibility and construct validity of the TIQ-20 were assessed.
RESULTS: The TIQ-20 responses fit the Rasch model and demonstrated
unidimensionality, adequate precision, absence of differential item functioning
and adequate person separation index. The TIQ-20 included items related to pain,
activity limitation, footwear modification, participation, psychological impact
and healthcare use due to tophi. In the 103 patients with tophaceous gout, floor
effects were observed in 4.9% and ceiling effects in 1%. The TIQ-20 test-retest
intraclass correlation coefficient was 0.76 (95% CI 0.61 to 0.85). All predicted
correlations for construct validity testing were observed, including weak
correlation with serum urate concentrations (r<0.30), moderate correlation with
subcutaneous tophus count and dual energy CT urate volume (r=0.30-0.50), and
stronger correlation with Health Assessment Questionnaire scores (r>0.50).
CONCLUSIONS: We have developed a tophus-specific PRO in patients with tophaceous
gout. The TIQ-20 demonstrates acceptable psychometric properties. Initial results
show internal, face and construct validity, reproducibility and feasibility.
Further research is required to determine responsiveness to change.
PMID- 25114060
TI - Safety, tolerability and potential efficacy of injection of autologous adipose
derived stromal vascular fraction in the fingers of patients with systemic
sclerosis: an open-label phase I trial.
AB - BACKGROUND: In patients with systemic sclerosis (scleroderma, SSc), impaired hand
function greatly contributes to disability and reduced quality of life, and is
insufficiently relieved by currently available therapies. Adipose tissue-derived
stromal vascular fraction (SVF) is increasingly recognised as an easily
accessible source of regenerative cells with therapeutic potential in ischaemic
or autoimmune diseases. We aimed to measure for the first time the safety,
tolerability and potential efficacy of autologous SVF cells local injections in
patients with SSc with hand disability. METHODS: We did an open-label, single
arm, at one study site with 6-month follow-up among 12 female SSc patients with
Cochin Hand Function Scale score >20/90. Autologous SVF was obtained from
lipoaspirates, using an automated processing system, and subsequently injected
into the subcutaneous tissue of each finger in contact with neurovascular
pedicles. Primary outcome was the number and the severity of adverse events
related to SVF-based therapy. Secondary endpoints were changes in hand disability
and fibrosis, vascular manifestations, pain and quality of life from baseline to
2 and 6 months after cell therapy. FINDINGS: All enrolled patients had surgery,
and there were no dropouts or patients lost to follow-up. No severe adverse
events occurred during the procedure and follow-up. Four minor adverse events
were reported and resolved spontaneously. A significant improvement in hand
disability and pain, Raynaud's phenomenon, finger oedema and quality of life was
observed. INTERPRETATION: This study outlines the safety of the autologous SVF
cells injection in the hands of patients with SSc. Preliminary assessments at 6
months suggest potential efficacy needing confirmation in a randomised placebo
controlled trial on a larger population. FUNDING: GFRS (Groupe Francophone de
Recherche sur la Sclerodermie). CLINICAL TRIALS NUMBER: NCT01813279.
PMID- 25114063
TI - Electrogram-gated radiofrequency ablations with duty cycle power delivery negate
effects of ablation catheter motion.
AB - BACKGROUND: Cardiac and respiratory movements cause catheter instability. Lateral
catheter sliding over target endocardial surface can lead to poor tissue contact
and unpredictable lesion formation. We describe a novel method of overcoming the
effects of lateral catheter sliding movements using an electrogram-gated pulsed
power ablation. METHODS AND RESULTS: All ablations were performed on a
thermochromic gel myocardial phantom. Ablation settings were randomized to
conventional (nongated) 30 W versus electrogram-gated at 20% duty cycle (30 W
average power) at 0-, 3-, 6-, and 9-mm lateral sliding distances. Forty-eight
radiofrequency ablations were performed. Deeper lesions were created in
electrogram-gated versus conventional ablations at 3 mm (4.36+/-0.08 versus
4.05+/-0.17 mm; P=0.009), 6 mm (4.39+/-0.10 versus 3.44+/-0.15 mm; P<0.001), and
9 mm (4.41+/-0.06 versus 2.94+/-0.16 mm; P<<0.001) sliding distances. Electrogram
gated ablations created consistent lesions at a quicker rate of growth in depth
when compared with conventional ablations (P<0.001). CONCLUSIONS: (1) Lesion
depth decreases and length increases in conventional ablations with greater
degrees of lateral catheter movements; (2) electrogram-gated pulsed
radiofrequency delivery negated the effects from lateral catheter movement by
creating consistently deeper lesions irrespective of the degree of catheter
movement; and (3) target lesion depths were reached significantly faster in
electrogram-gated than in conventional ablations.
PMID- 25114064
TI - Deafblindness: a review of the literature.
AB - BACKGROUND: Deafblindness or dual sensory loss is a rare condition among young
people, but more frequent among older people. Deafblindness is a heterogeneous
condition that varies with regard to time of onset and degree of vision and
hearing impairment, as well as communication mode, medical aetiology, and number
and severity of co-morbidity. METHOD: We conducted a comprehensive review of
public health issues related to deafblindness. RESULTS: Deafblindness often lead
to barriers in language and communication, access to information and social
interaction, which can lead to a number of health-related difficulties. Some of
the reported consequences are a higher risk of depression, cognitive decline,
developmental disorder in children and psychological distress. CONCLUSIONS:
Deafblindness is associated with a number of health-related issues and more
knowledge is needed about the impact of dual sensory loss to be able to offer the
best support.
PMID- 25114062
TI - Adverse remodeling of the electrophysiological response to ischemia-reperfusion
in human heart failure is associated with remodeling of metabolic gene
expression.
AB - BACKGROUND: Ventricular arrhythmias occur more frequently in heart failure during
episodes of ischemia-reperfusion although the mechanisms underlying this in
humans are unclear. We assessed, in explanted human hearts, the remodeled
electrophysiological response to acute ischemia-reperfusion in heart failure and
its potential causes, including the remodeling of metabolic gene expression.
METHODS AND RESULTS: We optically mapped coronary-perfused left ventricular wedge
preparations from 6 human end-stage failing hearts (F) and 6 donor hearts
rejected for transplantation (D). Preparations were subjected to 30 minutes of
global ischemia, followed by 30 minutes of reperfusion. Failing hearts had
exaggerated electrophysiological responses to ischemia-reperfusion, with greater
action potential duration shortening (P<0.001 at 8-minute ischemia; P=0.001 at 12
minute ischemia) and greater conduction slowing during ischemia, delayed recovery
of electric excitability after reperfusion (F, 4.8+/-1.8 versus D, 1.0+/-0
minutes; P<0.05), and incomplete restoration of action potential duration and
conduction velocity early after reperfusion. Expression of 46 metabolic genes was
probed using custom-designed TaqMan arrays, using extracted RNA from 15 failing
and 9 donor hearts. Ten genes important in cardiac metabolism were downregulated
in heart failure, with SLC27A4 and KCNJ11 significantly downregulated at a false
discovery rate of 0%. CONCLUSIONS: We demonstrate, for the first time in human
hearts, that the electrophysiological response to ischemia-reperfusion in heart
failure is accelerated during ischemia with slower recovery after reperfusion.
This can enhance spatial conduction and repolarization gradients across the
ischemic border and increase arrhythmia susceptibility. This adverse response was
associated with downregulation of expression of cardiac metabolic genes.
PMID- 25114065
TI - A case of community-based fall prevention: Survey of organization and content of
minor home help services in Swedish municipalities.
AB - BACKGROUND: The aim of this study was to survey minor home help services provided
by Swedish municipalities with the main purpose to prevent fall injuries.
METHODS: If minor home help services were presented on the homepage of a
municipality, an initial telephone contact was taken. Thereafter a questionnaire
was administered, including questions about target groups, aim with the services,
tasks included, costs and restrictions for users, budget, and experienced gains
with the services. Municipalities not providing minor home help services were
asked about the reason therefore and if the municipality had previously provided
the services Results: The questionnaire response rate was 92%. In 191 of Sweden's
290 municipalities services were provided by, or in cooperation with, the
municipality. Reasons for not providing the services were mainly financial and
lack of demand. Services were more often provided in larger cities and in
municipalities located in populous regions. In some municipalities services were
performed by persons with functional disabilities or unemployed persons.
CONCLUSIONS: Both providers and users expressed satisfaction with the services
aspects expressed were that services lead to greater sense of safety and social
gains the effect of the services in terms of fall prevention is yet to be proved
with only a small fall-preventive effect services are probably cost-effective
improved quality of life, sense of safety, and being able to offer meaningful
work to otherwise unemployed persons are important aspects that might in
themselves motivate the provision of minor home help services.
PMID- 25114066
TI - The association between erectile dysfunction, depressive symptoms and
testosterone levels among middle-aged men.
AB - AIMS: The aim of this study was to investigate the association between erectile
dysfunction and depressive symptoms and testosterone levels among middle-aged men
at the community level. METHODS: The study population consisted of 614 men born
in 1945 and living in the city of Oulu, Finland. Erectile dysfunction was
assessed by the erectile function domain of the International Index of Erectile
Function questionnaire and depressive symptoms by the Beck Depression Inventory.
Blood samples were collected to measure testosterone and sex hormone-binding
globulin level. RESULTS: After adjusting for confounders, erectile dysfunction
was statistically significantly associated with depressive symptoms (risk ratio
(RR) 1.66, 95% confidence interval (95% CI) 1.29-2.15), as well as with obesity
(RR 1.72, 95% CI 1.12-2.62). Neither total nor free testosterone level was
associated with erectile dysfunction among our study group. CONCLUSIONS:
Depressive symptoms rather than testosterone levels should be taken into
consideration while treating middle-aged men with erectile problems at the
community level.
PMID- 25114067
TI - Divorce and risk of hospital-diagnosed infectious diseases.
AB - BACKGROUND: Although, divorce is considered to have a negative impact on
morbidity, very little is known concerning exposure to divorce and risk of
infectious diseases. We aimed to investigate the association between divorce and
subsequent hospital contacts with infectious diseases. METHODS: We performed a
nation-wide cohort study, including all Danish men and women (n~5.6 million)
alive on the 1 January 1982 or later, and followed them for infectious disease
diagnosed in hospital settings from 1982 to 2010. The association between divorce
and risk of infectious diseases was evaluated through rate ratios (RRs) comparing
incidence rates of infectious diseases between divorced and married pesons.
RESULTS: Compared with married persons, divorced persons were overall at a 1.48
fold (RR=1.48 (95% CI: 1.47-1.50)) increased risk of hospital-diagnosed
infectious diseases (RR adjusted for sex, age, period, income and education). The
risk of infectious diseases was slightly more pronounced for divorced women
(RR=1.54 (1.52-1.56)) than divorced men ((RR=1.42 (1.41-1.44)). The increased
risk remained almost unchanged even more than 15 years after the divorce. Young
age at divorce, short duration of marriage and number of divorces further
increased the risk of infectious diseases, whereas number of children at time of
divorce had no impact on risk of hospital-diagnosed infectious diseases following
the divorce. CONCLUSIONS: Divorce appears to have a moderate but long lasting
impact on the risk of infectious diseases the underlying mechanism is unknown but
shared risk factors predicting divorce and infectious diseases could contribute
to our findings.
PMID- 25114069
TI - Inhibition of glutaminyl cyclase ameliorates amyloid pathology in an animal model
of Alzheimer's disease via the modulation of gamma-secretase activity.
AB - Alzheimer's disease is the most prevalent neurodegenerative disorder,
characterized by neurofibrillary tangles, senile plaques, and neuron loss.
Amyloid beta peptides are generated from amyloid beta precursor protein by
consecutive catalysis by beta and gamma-secretases. Diversely modified forms of A
have been N3pE-42 Abeta has received considerable attention as one of the major
constituents of the senile plaques of AD brains due to its higher aggregation
velocity, stability, and hydrophobicity compared to the full-length A. A previous
study suggested that is catalyzed by glutaminyl cyclase (QC) following limited
proteolysis of Abeta at the N-terminus. Here, we reveal that decreasing the QC
activity via application of a QC inhibitor modulates-gamma-secretase activity,
resulting in diminished plaque formation as well as reduced N3pE 42 Abeta
aggregates in the subiculum of the 5XFAD mouse model of AD. This study suggests a
possible novel mechanism by which QC regulates Abeta formation , namely
modulation of gamma-secretase activity.
PMID- 25114068
TI - Genetic determinants of disease progression in Alzheimer's disease.
AB - There is a strong genetic basis for late-onset Alzheimer's disease (LOAD); thus
far 22 genes/loci have been identified that affect the risk of LOAD. However, the
relationships among the genetic variations at these loci and clinical progression
of the disease have not been fully explored. In the present study, we examined
the relationships of 22 known LOAD genes to the progression of AD in 680 AD
patients recruited from the University of Pittsburgh Alzheimer's Disease Research
Center. Patients were classified as "rapid progressors" if the Mini-Mental State
Examination (MMSE) changed >=3 points in 12 months and "slow progressors" if the
MMSE changed <=2 points. We also performed a genome-wide association study in
this cohort in an effort to identify new loci for AD progression. Association
analysis between single nucleotide polymorphisms (SNPs) and the progression
status of the AD cases was performed using logistic regression model controlled
for age, gender, dementia medication use, psychosis, and hypertension. While no
significant association was observed with either APOE*4 (p = 0.94) or APOE*2 (p =
0.33) with AD progression, we found multiple nominally significant associations
(p < 0.05) either within or adjacent to seven known LOAD genes (INPP5D, MEF2C,
TREM2, EPHA1, PTK2B, FERMT2, and CASS4) that harbor both risk and protective
SNPs. Genome-wide association analyses identified four suggestive loci (PAX3,
CCRN4L, PIGQ, and ADAM19) at p < 1E-05. Our data suggest that short-term clinical
disease progression in AD has a genetic basis. Better understanding of these
genetic factors could help to improve clinical trial design and potentially
affect the development of disease modifying therapies.
PMID- 25114070
TI - Brain changes within the visuo-spatial attentional network in posterior cortical
atrophy.
AB - Posterior cortical atrophy (PCA) is characterized by basic visual and high order
visual-spatial dysfunctions. In this study, we investigated long-distance
deafferentation processes within the frontal-parietal-occipital network in ten
PCA patients using a MRI-PET combined approach. Objective voxel-based [18F]FDG
PET imaging measured metabolic changes in single patients. Comprehensive
investigation of diffusion tensor imaging (DTI) metrics and grey-matter density
with voxel-based morphometry were obtained in a subgroup of 6 patients.
Fractional anisotropy in the superior longitudinal fasciculus correlated with the
PET metabolic changes within the inferior parietal and frontal eye field regions.
[18F]FDG-PET analysis showed in each PCA case the typical bilateral hypometabolic
pattern, involving posterior temporal, parietal, and occipital cortex, with
additional hypometabolic foci in the frontal eye fields. Voxel-based morphometry
showed right-sided atrophy in the parieto-occipital cortex, as well as a limited
temporal involvement. DTI revealed extensive degeneration of the major anterior
posterior connecting fiber bundles and of commissural frontal lobe tracts.
Microstructural measures in the superior longitudinal fasciculus were correlated
with the PET metabolic changes within the inferior parietal and frontal eye field
regions. Our results confirmed the predominant occipital-temporal and occipital
parietal degeneration in PCA patients. [18F]FDG-PET and DTI-MRI combined
approaches revealed neurodegeneration effects well beyond the classical posterior
cortical involvement, most likely as a consequence of deafferentation processes
within the occipital-parietal-frontal network that could be at the basis of visuo
perceptual, visuo-spatial integration and attention deficits in PCA.
PMID- 25114071
TI - Classification of non-demented patients attending a memory clinic using the new
diagnostic criteria for Alzheimer's disease with disease-related biomarkers.
AB - BACKGROUND: New diagnostic criteria for predemential Alzheimer's disease (AD)
advocate the use of biomarkers. However, the benefit of using biomarkers has not
been clearly demonstrated in clinical practice. OBJECTIVE: To investigate whether
a combination of biomarkers may be helpful in classifying a population of non
demented patients attending a Memory Clinic. METHODS: Sixty non-demented patients
were compared with 31 healthy elderly subjects. All subjects underwent a
neuropsychological examination, brain 3T magnetic resonance imaging, [F18]
fluorodeoxyglucose and [F18]-flutemetamol positron emission tomography. According
to their performance on memory, language, executive, and visuo-spatial domains,
the patients were classified as mild cognitive impairment (amnestic, non
amnestic, single, or multiple domain) or subjective cognitive impairment.
Patients were then classified according to the National Institute on Aging
Alzheimer's Association (NIA-AA) criteria, using the normalized mean hippocampal
volume (Freesurfer), [F18]-FDG PALZAD, and [F18]-flutemetamol standard uptake
value ratio (SUVr) (cut-off at the 10th percentile of controls). The standard of
truth was the clinical status at study entry (patient versus control). RESULTS:
The sensitivity/specificity of the clinical classification was 65/84%. The NIA-AA
criteria were applicable in 85% of patients and 87% of controls. For biomarkers
the best sensitivity (72%) at a fixed specificity of 84% was achieved by a
combination of the three biomarkers. The clinical diagnosis was reconsidered in
more than one third of the patients (42%) as a result of including the biomarker
results. CONCLUSIONS: Application of the new NIA-AA AD diagnostic criteria based
on biomarkers in an unselected sample of non-demented patients attending a Memory
Clinic was useful in allowing for a better classification of the subjects.
PMID- 25114072
TI - A candidate plasma protein classifier to identify Alzheimer's disease.
AB - Biomarkers currently used in the aid for the diagnosis of Alzheimer's disease
(AD) are cerebrospinal fluid (CSF) protein markers and brain neuroimaging
markers. These biomarkers, however, either involve semi-invasive procedures or
are costly to measure. Thus, AD biomarkers from more easily accessible body
fluids, such as plasma, are very enticing. Using an aptamer-based proteomic
technology, we profiled 1,129 plasma proteins of AD patients and non-demented
control individuals. A 5-protein classifier for AD identification was constructed
in the discovery study with excellent 10-fold cross-validation performance (90.1%
sensitivity, 84.2% specificity, 87.9% accuracy, and AUC as 0.94). In an
independent validation study, the classifier was applied and correctly predicted
AD with 100.0% sensitivity, 80.0% specificity, and 90.0% accuracy, matching or
outperforming the CSF Abeta42 and tau biomarkers whose performance were assessed
in individual-matched CSF samples obtained at the same visit as plasma sample
collection. Moreover, the classifier also correctly predicted mild cognitive
impairment, an early pre-dementia state of the disease, with 96.7% sensitivity,
80.0% specificity, and 92.5% accuracy. These studies demonstrate that plasma
proteins could be used effectively and accurately to contribute to the clinical
diagnosis of AD. Although additional and more diverse cohorts are needed for
further validation of the robustness, including the support of postmortem
diagnosis, the 5-protein classifier appears to be a promising blood test to
contribute diagnosis of AD.
PMID- 25114073
TI - Increased permeability of the blood-brain barrier and Alzheimer's disease-like
alterations in slit-2 transgenic mice.
AB - Alzheimer's disease (AD) is a progressive neurological disorder that primarily
affects memory, and its prevalence is rising. Increasing evidence suggests that
dysfunction of the blood-brain barrier (BBB) may be involved in AD and other
neurodegenerative diseases. Herein, we report that the permeability of the BBB is
increased and that AD-like alterations are present in Slit-2 overexpressing
transgenic mice. We found that behavioral change and the corresponding molecular
diagnostic markers of AD, such as hippocampal neuron apoptosis, amyloid-beta
(Abeta) protein deposition, and acetylcholinesterase expression, were increased
in the Slit-2 transgenic mice. Moreover, the endothelial cells were
dysfunctional, the size of the lateral ventricle cavity increased, and the
permeability of the BBB increased. Additionally, there was an increased serum
level of glutamate indicating that the BBB is related to AD. Finally,
histopathological analysis of other organs in the Slit-2 overexpressing mice did
not show any marked abnormalities. These findings demonstrate that Slit2
overexpression may be responsible for AD-like alterations and the increased BBB
permeability in these mice. Our study provides a potential novel mechanism for
the development of AD.
PMID- 25114074
TI - Optimizing regions-of-interest composites for capturing treatment effects on
brain amyloid in clinical trials.
AB - BACKGROUND: Pittsburgh Compound B (PiB) positron emission tomography (PET)
neuroimaging is a powerful research tool to characterize amyloid evolution in the
brain. Quantification of amyloid load critically depends on (i) the choice of a
reference region (RR) and (ii) on the selection of regions of interest (ROIs) to
derive the standard uptake value ratios (SUVRs). OBJECTIVE: To evaluate the
stability, i.e., negligible amyloid accumulation over time, of different RRs, and
the performance of different PiB summary measures defined by selected ROIs and
RRs for their sensitivity to detecting longitudinal change in amyloid burden.
METHODS: To evaluate RRs, cross-sectional and longitudinal analyses of focal
regional and composite measures of amyloid accumulation were carried out on the
standardized PiB-PET regional data for cerebellar grey matter (CER), subcortical
white matter (SWM), and pons (PON). RRs and candidate composite SUVR measures
were further evaluated to select regions and develop novel composites, using
standardized 2-year change from baseline. RESULTS: Longitudinal trajectories of
PiB4-average of anterior cingulate (ACG), frontal cortex (FRC), parietal cortex,
and precuneus-demonstrated marked variability and small change from baseline when
normalized to CER, larger changes and less variability when normalized to SWM,
which was further enhanced for the composite in PON-normalized settings. Novel
composite PiB3, comprised of the average SUVRs of lateral temporal cortex, ACG,
and FRC was created. CONCLUSION: PON and SWM appeared to be more stable RRs than
the CER. PiB3 showed compelling sample size reduction and gains in power
calculations for clinical trials over conventional PiB4 composite.
PMID- 25114075
TI - AMPK activation ameliorates Alzheimer's disease-like pathology and spatial memory
impairment in a streptozotocin-induced Alzheimer's disease model in rats.
AB - Collecting evidence has shown that type 2 diabetes mellitus is a high risk factor
of late-onset Alzheimer's disease (AD); the energy metabolic dysfunction is
thought to be a convergent point of the two diseases. However, the underlying
mechanisms of diabetes-associated AD are still unclear. In the current study, we
investigated the roles of AMPK in diabetes-related AD-like pathologic features in
models of intracerebroventricular-streptozotocin (ICV-STZ) animals. Rats infused
with STZ (3 mg/kg, once) were followed by injection of AICAR (AMPK activator) or
vehicle via ICV. We found that the level of p-AMPK (active type of AMPK) and
SIRT1 activity were decreased and the level of phosphorylated tau was increased
at Ser396 and Thr231 sites in ICV-STZ rats when compared with control rats.
Mitochondria from ICV-STZ rats displayed a significant decrease in mitochondrial
membrane potential, complex I activity, ATP level, and superoxide dismutase
activity as well as an increase of reactive oxygen species production when
compared with that from control rats. Meanwhile the number of apoptotic cell
confirmed by cleaved caspase-3 (active type of caspase-3) staining was also
stronger in ICV-STZ rats than control rats. All pathological changes including
biochemistry and cognitive function could be mitigated through rescuing AMPK
activity with its specific activator (AICAR) in ICV-STZ rats. Taken together,
these results suggested that AMPK activation improves AD-like pathological
changes via repairing mitochondrial functions in ICV-STZ rats.
PMID- 25114076
TI - Amyloid-beta related memory decline is not associated with subjective or
informant rated cognitive impairment in healthy adults.
AB - BACKGROUND: The detection of early Alzheimer's disease (AD) can rely on
subjective and informant reports of cognitive impairment. However, relationships
between subjective cognitive impairment, objectively measured cognitive function,
and amyloid-beta (Abeta) biomarkers remain unclear. OBJECTIVE: To determine the
extent to which impairment or decline in subjective and informant rated cognitive
impairment was associated with memory in healthy older adults with high Abeta.
METHODS: Healthy older adults (n = 289) enrolled in the Australian Imaging,
Biomarkers and Lifestyle (AIBL) study were studied at baseline. Pittsburgh
Compound B was used to determine Abeta status at baseline. At baseline and 18
months assessments, subjective memory impairment was assessed using the Memory
Complaint Questionnaire and the Short Form of the Informant Questionnaire on
Cognitive Decline in the Elderly. Cognition was measured using the Cogstate Brief
Battery. RESULTS: At baseline, there were no differences between low and high
Abeta groups in subjective or informant-rated cognitive impairment, depressive
and anxiety symptoms, or cognitive function. Longitudinal analyses showed
moderate decline in learning and working memory over the 18 months in the high
Abeta group. However there was no change over time in subjective or informant
rated cognitive impairment, depressive and anxiety symptoms, or cognition in
either Abeta group. CONCLUSIONS: Although healthy older adults with high Abeta
levels show decline in learning and working memory over 18 months, subjective or
informant ratings of cognitive impairment do not change over the same period
suggesting subjective cognitive impairment may have limited utility for the very
early identification of AD.
PMID- 25114077
TI - Default mode network connectivity patterns associated with visual processing at
different stages of Parkinson's disease.
AB - BACKGROUND: The default mode network (DMN) decreases its activity when switching
from a resting state to a cognitive task condition, while activity of the network
engaged in the given task increases. Visual processing is typically disturbed in
Parkinson's disease dementia (PDD). OBJECTIVE: Using functional MRI, we studied
the DMN effective connectivity patterns in PDD as compared with cognitively
normal patients with Parkinson's disease (PD) and healthy controls (HC) when
switching from baseline to a visual cognitive task condition. METHODS: In all, 14
PDD, 18 PD, and 18 age-matched healthy controls participated in this functional
MRI study. We used a psychophysiological interaction analysis with the precuneus
(PCu) as a seed. The threshold was set at p(FWE) <0.05. RESULTS: The healthy
controls showed greater PCu connectivity with the bilateral middle
temporal/middle occipital gyri at baseline than during the task condition. The
correlation direction changed from positive to negative. Both PD and PDD showed
disturbed DMN connectivity with the brain regions that are involved in bottom-up
visual processing. In PD, we also found impaired integration of the areas engaged
in the ventral attentional network, which might reflect specific attentional
deficits observed during the early course of PD. In mild PDD, we detected
increased engagement of areas involved in the dorsal attentional network, which
corresponds to increased top-down control in this patient group as compared to
the healthy controls. CONCLUSION: Our results show impaired dynamic interplay
between large scale brain networks in PD that spread far beyond the motor system.
PMID- 25114078
TI - Cholinergic subcortical hyperintensities in Alzheimer's disease patients from the
Sunnybrook Dementia Study: relationships with cognitive dysfunction and
hippocampal atrophy.
AB - BACKGROUND: Subcortical hyperintensities within the cholinergic fiber projections
(chSH) on MRI are believed to reflect cerebral small vessel disease (SVD) which
may adversely impact cognition. Additionally, hippocampal atrophy represents a
commonly used biomarker to support the diagnosis of Alzheimer's disease (AD).
OBJECTIVE: To examine potential differences in neuropsychological test
performance between AD patients (n = 234) with high and low chSH volumes and
whether these differences corresponded to hippocampal atrophy. METHODS: A
modified version of Lesion Explorer was used to volumetrically quantify chSH
severity. The Sunnybrook Hippocampal Volumetry Tool was applied to obtain
hippocampal volumes. Composite z-scores to assess executive, memory, and
visuospatial functioning were generated from standardized neuropsychological test
performance scores. RESULTS: Inter-method technique validation demonstrated a
high degree of correspondence with the Cholinergic Pathways Hyperintensities
Scale (n = 40, rho = 0.84, p < 0.001). After adjusting for brain atrophy, disease
severity, global SH volumes, and demographic variables, multivariate analyses
revealed a significant group difference, with the high chSH group demonstrating
poorer memory function compared to the low chSH group (p = 0.03). A significant
difference was found between low and high chSH groups in total (p < 0.05) and
left (p < 0.01) hippocampal volume. CONCLUSION: These results suggest degradation
of the cholinergic projections due to strategic SVD may independently contribute
to memory dysfunction and hippocampal atrophy. Future studies examining
subcortical vasculopathy in the cholinergic pathways may have implications on the
development of therapeutic strategies for dementia and SVD.
PMID- 25114079
TI - Efficacy and adverse effects of ginkgo biloba for cognitive impairment and
dementia: a systematic review and meta-analysis.
AB - BACKGROUND: Research into Ginkgo biloba has been ongoing for many years, while
the benefit and adverse effects of Ginkgo biloba extract EGb761 for cognitive
impairment and dementia has been discussed controversially. OBJECTIVE: To discuss
new evidence on the clinical and adverse effects of standardized Ginkgo biloba
extract EGb761 for cognitive impairment and dementia. METHODS: MEDLINE, EMBASE,
Cochrane, and other relevant databases were searched in March 2014 for eligible
randomized controlled trials of Ginkgo biloba EGb761 therapy in patients with
cognitive impairment and dementia. RESULTS: Nine trials met our inclusion
criteria. Trials were of 22-26 weeks duration and included 2,561 patients in
total. In the meta-analysis, the weighted mean differences in change scores for
cognition were in favor of EGb761 compared to placebo (-2.86, 95%CI -3.18;
2.54); the standardized mean differences in change scores for activities in daily
living (ADLs) were also in favor of EGb761 compared to placebo (-0.36, 95%CI
0.44; -0.28); Peto OR showed a statistically significant difference from placebo
for Clinicians' Global Impression of Change (CGIC) scale (1.88, 95%CI 1.54;
2.29). All these benefits are mainly associated with EGb761 at a dose of 240
mg/day. For subgroup analysis in patients with neuropsychiatric symptoms, 240
mg/day EGb761 improved cognitive function, ADLs, CGIC, and also neuropsychiatric
symptoms with statistical superiority than for the whole group. For the
Alzheimer's disease subgroup, the main outcomes were almost the same as the whole
group of patients with no statistical superiority. Finally, safety data revealed
no important safety concerns with EGb761. CONCLUSIONS: EGb761 at 240 mg/day is
able to stabilize or slow decline in cognition, function, behavior, and global
change at 22-26 weeks in cognitive impairment and dementia, especially for
patients with neuropsychiatric symptoms.
PMID- 25114081
TI - Transmembrane protein 106B gene (TMEM106B) variability and influence on
progranulin plasma levels in patients with Alzheimer's disease.
AB - We carried out an association study of transmembrane protein 106B gene (TMEM106B)
rs1020004 A/G, rs6966915C/T, and rs1990622 A/G in a population of 656 patients
with Alzheimer's disease (AD) and 619 controls, and tested whether the rs1990622
influences plasma progranulin levels. No differences in allele and genotype
distribution were observed between cases and controls, even stratifying according
to APOE status (p > 0.05). No differences in progranulin plasma levels were found
between carriers of the rs1990622 and non-carriers. TMEM106b variability does not
influence AD risk or plasma levels. Replication, preferably in a population with
pathological confirmation, is required to confirm these results.
PMID- 25114082
TI - Characterizing topological patterns in amnestic mild cognitive impairment by
quantitative water diffusivity.
AB - Mean diffusivity (MD) derived from diffusion tensor imaging has shown its ability
to assess the microscopic structural integrity damage of gray matter in amnestic
mild cognitive impairment (aMCI), a prodromal stage of Alzheimer's disease (AD).
However, little is known about the small world topology networks constructed by
cortical MD in cognitive disease. In this work, we measured the cortical MD in
the entire brain in patients with aMCI (n = 30) and AD (n = 30) compared with
cognitive-normal (CNs) controls (n = 30), and then constructed the cortical
diffusivity network by using graph-theoretical analysis. Compared with CNs,
patients with aMCI and AD showed abnormal small-world property of cortical
diffusivity networks (higher degree of clustering and longer path length),
reflecting a less optimal topological organization. Moreover, the mean degree of
connections of network in aMCI patients was characterized by lower than CNs but
higher than AD. In addition, 11 hub regions were identified by negative
correlations between MD and the score of Montreal Cognitive Assessment after
multiple regression analysis, including bilateral hippocampi and related limbic
system. Among those hub regions, the connectivity of the right olfactory cortex
and middle orbital gyrus to the rest of brain regions were disrupted earlier than
the other 9 regions in aMCI when compared to CN. In conclusion, the change of
cortical diffusivity in topological network organization, mean degree of
connections, and disrupted hub regions in aMCI may serve to identify patients in
the prodromal stage of AD and reflect microstructural deterioration of
neurodegeneration.
PMID- 25114080
TI - Overexpression of heme oxygenase 1 causes cognitive decline and affects pathways
for tauopathy in mice.
AB - The stress protein heme oxygenase-1 (HO-1) is upregulated and co-localizes to
pathological features, including tauopathies in the brains of individuals with
Alzheimer's disease. However, the relationship between HO-1 and Alzheimer's
disease remains unclear. In our previous research, the long-term overexpression
of HO-1 was shown to promote tau aggregation by inducing tau phosphorylation in
the mouse brain. In this study, we found that the long-term overexpression of HO
1 led to cognitive decline in transgenic mice, as determined by the water maze
test, and that HO-1 can affect two pathways for tauopathy. Through one pathway,
HO-1 promotes the expression of CDK5 by accumulating reactive oxygen species,
which are produced by HO-1 downstream products of iron in neuro2a cell lines and
mouse brain. Through the second pathway, HO-1 induces tau truncation at D421 in
vivo and in vitro. Clearly, there is a HO-1-dependent mechanism responsible for
tau protein phosphorylation and tau truncation in vivo and in vitro. Taken
together, our results suggest that HO-1 plays an important role in the disease
process of tauopathies in AD.
PMID- 25114084
TI - Contributions of a risk assessment approach to the prevention of Alzheimer's
disease and dementia.
AB - The development and integration of risk assessment and clinical risk management
for Alzheimer's disease (AD) and dementia is a rapidly emerging field of research
and practice. At present, risk management is the only available approach with
potential for a large impact on the projected rates of dementia, given population
aging. This review describes six available risk assessment tools, including those
developed specifically for AD and those for dementia. These tools differ along
several important dimensions, including whether they (a) include clinical
measures, (b) require a clinician's ratings, (c) are predominantly self-report,
(d) are independently validated, and (e) are available online. A narrative review
of recently identified risk factors not included in these instruments is
included, indicating future directions for risk assessment. Finally,
consideration is given to the prioritization of risk advice according to the ease
of risk modification and the potential for synergies among risk factors.
PMID- 25114085
TI - Cognitively-based methods of enhancing and maintaining functioning in those at
risk of Alzheimer's disease.
AB - Projections indicate that the prevalence of Alzheimer's disease (AD) and other
dementias will increase two to three fold in the coming decades. As a result,
there has been considerable interest in identifying methods that maintain or
enhance cognitive functioning in these older adults. Existing pharmacological
agents are limited in this respect and disease-modifying agents are years away
from being available. Cognitively based interventions (i.e., cognitive training,
cognitive rehabilitation) hold particular promise for maximizing patients'
functioning, are relatively inexpensive, and have virtually no side effects.
Everyday life is complex and multifaceted, which means that a personalized
approach is essential for maximizing and prolonging functioning in each patient.
Unfortunately, little is known about the factors contributing to such an
approach. The current review first identifies several lifestyle factors that have
been shown to be neuroprotective as well as risk factors that may ultimately
contribute to the efficacy of different cognitive intervention techniques. There
is a critical need to understand the conditions under which individual techniques
are effective; an issue examined through characteristic examples across the AD
spectrum. While limited at this time, there is some evidence of the long-term
benefits of cognitive intervention. We conclude by describing several critical
areas of investigation and proposing a clinically oriented framework for both
furthering cognitive intervention research and providing patient-centered care.
PMID- 25114083
TI - A phenotype of atypical apraxia of speech in a family carrying SQSTM1 mutation.
AB - SQSTM1 mutations, coding for the p62 protein, were identified as a monogenic
cause of Paget disease of bone and of amyotrophic lateral sclerosis. More
recently, SQSTM1 mutations were identified in few families with frontotemporal
dementia. We report a new family carrying SQSTM1 mutation and presenting with a
clinical phenotype of speech apraxia or atypical behavioral disorders, associated
with early visuo-contructional deficits. This study further supports the
implication of SQSTM1 in frontotemporal dementia, and enlarges the phenotypic
spectrum associated with SQSTM1 mutations.
PMID- 25114086
TI - Tofu intake is associated with poor cognitive performance among community
dwelling elderly in China.
AB - Tofu is a soy product which is commonly consumed in Asian countries, such as
China and Indonesia. Several studies found negative associations of high tofu
consumption with cognitive function in older Asian populations. However, the
effect of tofu on cognitive function remains disputed as it was not found in
Western populations. In the present study, the effect of weekly tofu intake on
cognitive performance was investigated in an observational cross sectional study
of 517 Chinese elderly from Shanghai. Similar to earlier studies, results showed
that a higher weekly intake of tofu was associated with worse memory performance
using the Hopkins Verbal Learning Test (beta = -0.10, p = 0.01) after controlling
for age, gender, education, being vegetarian, and weekly intake of fruit/juice,
green vegetables, and orange/red vegetables. Furthermore, among older elderly
(>=68 years of age), high tofu intake increased the risk of cognitive impairment
indicative of dementia (OR = 1.27, 95% CI = 0.99-1.64, p = 0.04), after adjusting
for all covariates. Consumption of meat and green vegetables independently also
reduced risk of dementia. To conclude, high intake of tofu was negatively related
to cognitive performance among community-dwelling elderly in China. Similar
findings were reported in Indonesia and in Japanese Americans in the US. These
findings suggest that the effect of tofu on cognition in elderly should be
further investigated.
PMID- 25114087
TI - The Florence VAS-COG clinic: a model for the care of patients with cognitive and
behavioral disturbances consequent to cerebrovascular diseases.
AB - BACKGROUND AND OBJECTIVE: Services dedicated to patients with cognitive and
behavioral consequences of cerebrovascular diseases are not well established. In
this paper, we report on the general organization of such a service (the Florence
VAS-COG Clinic) after 9 years of activity, updating a previous work related to
the first 5 years. METHODS: The Florence VAS-COG clinic, started in 2006, is an
outpatient service dedicated to the assessment and follow-up of patients with
cerebrovascular diseases and related cognitive, psychiatric, and behavioral
disturbances. The staff involved in the clinic is composed of certified
neurologists, one neuropsychologist, and neurology residents. The diagnostic
protocol includes detailed personal and family history, general and neurologic
examinations, and functional, neuropsychological, and neuroimaging assessment.
After this work-up, comprehensive diagnoses are made. RESULTS: From January 2006
to March 2014, 600 patients (mean age 67.3 years +/- 13.9; 52% females) have been
evaluated in the clinic. Cognitive impairment, including mild cognitive
impairment and dementia, mainly of vascular origin, was the most common (36.4%)
diagnostic category, followed by suspected or confirmed familial micro-angiopathy
(35.8%). Compared to the first years of activity, we are now facing the need of
augmenting the number of visits due to increasing request and to better implement
the multidisciplinarity of the team. Efforts are currently directed towards the
definition of management protocols in pharmacological and non-pharmacological
strategies. CONCLUSIONS: The establishment of a VAS-COG clinic represents an
important step for the appreciation of the patient clinical needs and for the
implementation of screening, diagnostic, and treatment options in the field of
the neuropsychiatric consequences of cerebrovascular diseases.
PMID- 25114089
TI - In-house heart-brain clinics to reduce Alzheimer's disease incidence.
AB - The incidence rate in Alzheimer's disease (AD) is expected to quadruple worldwide
by 2050. To limit this impending socio-medical calamity, a fulcrum change from
how AD is presently managed is crucial. The present approach has not averted the
stress of AD on medical resources nor reduced the already cost-strained
government health care programs. Since substantial evidence indicates that
sporadic AD is directly associated with vascular risk factors, a strategic plan
is proposed to target this association and markedly reduce the onset of AD. This
plan would establish in-house heart-brain clinics devoted to identifying,
detecting, and preventing the progression of vascular risk factors that
predispose to cognitive impairment and development of AD. The heart-brain clinics
would be staffed with a multidisciplinary group of neurologists, psychologists,
neuroradiologists, cardiovascular specialists, and technical personnel Their goal
would be to apply and interpret non-invasive, cost-effective multidiagnostic
testing of heart and brain function in outpatient asymptomatic and symptomatic
patients at risk of dementia. Multidiagnostic testing would permit better risk
stratification, medical decision-making, and a tailored intervention of patients
at-risk of dementia than the present monotherapeutic approach. Personalized
intervention, moreover, should achieve better patient compliance and outcome
through periodic follow-up visits to the clinics where the medical plan of action
could be monitored and modified as needed. Multidisciplinary heart-brain clinics
will be costly at first but eventually should become cost-effective while
providing an invaluable medical service to an aging population and possibly
extending years of full-health lived in those at risk of dementia.
PMID- 25114090
TI - The interaction of APOE genotype by age in amnestic mild cognitive impairment: a
voxel-based morphometric study.
AB - The apolipoprotein E (APOE) gene has been confirmed as the major genetic risk
factor for the conversion of amnestic mild cognitive impairment (aMCI) to
Alzheimer's disease (AD). The present study was to assess whether there was a
specific interaction of APOE by the aging process on brain morphology in aMCI.
The analysis of gray matter (GM) voxel-based morphometry was performed in 85 aMCI
and 100 healthy controls (HC). A significant interaction of APOE genotype by age
on GM volume was found in the left calcarine, the left insula, and the left
medial frontal gyrus in aMCI. GM volume in aMCI decreased significantly with
epsilon 2-carriers < epsilon3/epsilon3 < epsilon4-carriers in above brain regions
(except the left insula) while there was only a reduced tendency in HC. The
multivariate regression analysis showed the well-known negative relationship for
epsilon4-carriers and the positive relationship for epsilon2-carriers (except the
left insula), while no correlations were found for epsilon3/epsilon3 between age
and GM volumes on above brain regions. Moreover, the reduced GM volumes in the
left calcarine and insula correlated with the impairment of visuo-spatial
cognition and episodic memory in epsilon4- and epsilon2-carriers but not
epsilon3/epsilon3, respectively. These results suggest that the APOE epsilon4 and
epsilon2 alleles have the opposing effects on brain morphology across the
spectrum of cognitive aging. Moreover, the interaction of APOE by age on brain
morphology may accelerate the pathological progression of late-life cognitive
decline in aMCI with epsilon4-carriers and delay the possible conversion from
aMCI with epsilon2-carriers to AD.
PMID- 25114091
TI - PTEN hamartoma tumour syndrome: early tumour development in children.
AB - OBJECTIVE: The aim of this study was to report the earliest age of diagnosis of
common clinical findings in children with PTEN hamartoma tumour syndrome (PHTS).
DESIGN: Medical records of children with PHTS were reviewed; data included growth
measurements, presence or absence of specific clinical manifestations and
tumours, and documented ages of diagnosis. SETTING: Children with PHTS evaluated
at Boston Children's Hospital from 1996 to 2011. PATIENTS: The cohort included 34
children diagnosed with PHTS via genetic testing, under the age of 21 years. Of
these, 23 were male and 11 female. The mean age at their last documented clinical
evaluation was 13.6 years. The mean follow-up time was 7.5 years. RESULTS:
Macrocephaly and developmental/intellectual disability were consistent findings.
Pigmented penile macules were noted in all males examined for this finding.
Thyroid nodules, found in half the children screened with ultrasound, were
diagnosed as early as at 5 years of age. Thyroid carcinoma, identified in 12% of
the children in this cohort, was diagnosed as early as at 7 years of age. Other
tumours included renal cell carcinoma diagnosed at 11 years of age and granulosa
cell tumour of the ovary and colonic ganglioneuroma, each diagnosed at 16 years
of age. CONCLUSIONS: Specific clinical findings and tumours are characteristic in
children with PHTS. Tumour development occurs in young children with this
condition, which necessitates early surveillance, especially of the thyroid.
PMID- 25114088
TI - Common mechanisms of Alzheimer's disease and ischemic stroke: the role of protein
kinase C in the progression of age-related neurodegeneration.
AB - Ischemic stroke and Alzheimer's disease (AD), despite being distinct disease
entities, share numerous pathophysiological mechanisms such as those mediated by
inflammation, immune exhaustion, and neurovascular unit compromise. An important
shared mechanistic link is acute and chronic changes in protein kinase C (PKC)
activity. PKC isoforms have widespread functions important for memory, blood
brain barrier maintenance, and injury repair that change as the body ages.
Disease states accelerate PKC functional modifications. Mutated forms of PKC can
contribute to neurodegeneration and cognitive decline. In some cases the PKC
isoforms are still functional but are not successfully translocated to
appropriate locations within the cell. The deficits in proper PKC translocation
worsen stroke outcome and amyloid-beta toxicity. Cross talk between the innate
immune system and PKC pathways contribute to the vascular status within the aging
brain. Unfortunately, comorbidities such as diabetes, obesity, and hypertension
disrupt normal communication between the two systems. The focus of this review is
to highlight what is known about PKC function, how isoforms of PKC change with
age, and what additional alterations are consequences of stroke and AD. The goal
is to highlight future therapeutic targets that can be applied to both the
treatment and prevention of neurologic disease. Although the pathology of
ischemic stroke and AD are different, the similarity in PKC responses warrants
further investigation, especially as PKC-dependent events may serve as an
important connection linking age-related brain injury.
PMID- 25114094
TI - A review of anomalous origination of a coronary artery from an opposite sinus of
Valsalva (ACAOS) impact on major adverse cardiovascular events based on coronary
computerized tomography angiography: a 6-year single center review.
AB - BACKGROUND: Anomalous origination of a coronary artery from an opposite sinus of
Valsalva (ACAOS) is a rare finding that is typically found on autopsy in a person
with sudden cardiac death or during routine cardiovascular testing. The true
prevalence is unknown for this reason. There is also question to the specific
anatomy of the anomalies themselves and how best to correct them. METHODS: We
performed a retrospective chart review of all coronary computed tomography
angiography (CCTA) studies to evaluate the incidence of all-cause mortality,
nonfatal myocardial infarction, stroke and late revascularization (>90 days
following CCTA) from January 2005 until July 2012. We describe the origin of the
artery, its course, slit-like appearance and treatment in this population.
RESULTS: We reviewed 1518 CCTA reports and identified 22 patients with ACAOS with
an incidence of 1.4% of our original study population over a review period of 6
years with a resultant median follow-up period of 25 months [interquartile range
(IQR)25,75 12-34 months]. The indication for CCTA was for chest pain in the
majority of patients (73%). We had one patient undergo surgical repair and one
with coronary bypass grafting for unrelated symptomatic coronary artery disease.
CONCLUSION: ACAOS continues to be a rare but presumed fatal condition in subsets
identified to carry high risk features. As the characteristics of the anomalous
vessels that increase risk are still debated, over an intermediate to long follow
up in a single large center, none of the different anomalous findings with
varying degrees of high risk findings were associated with sudden death.
PMID- 25114095
TI - A rare cause of cardiogenic shock: variant angina.
AB - Variant angina (VA) is a clinical syndrome caused by spontaneous vasospasm of the
epicardial coronary artery which is characterized by episodes of angina.
Endothelial dysfunction and neurohormonal hyperactivity are important factors in
pathogenesis of VA. Although patient prognosis is good, VA may be one of the
reasons of sudden cardiac death (SCD) in case of persistent ST segment elevation
and malignant arrhythmias. Therefore, early treatment of VA is crucial for
prevention of malignant arrhythmias and SCD. In this case report we describe a
case of VA presented with cardiogenic shock and malignant ventricular arrhythmia.
PMID- 25114092
TI - Direct measurement of the mechanical work during translocation by the ribosome.
AB - A detailed understanding of tRNA/mRNA translocation requires measurement of the
forces generated by the ribosome during this movement. Such measurements have so
far remained elusive and, thus, little is known about the relation between force
and translocation and how this reflects on its mechanism and regulation. Here, we
address these questions using optical tweezers to follow translation by
individual ribosomes along single mRNA molecules, against an applied force. We
find that translocation rates depend exponentially on the force, with a
characteristic distance close to the one-codon step, ruling out the existence of
sub-steps and showing that the ribosome likely functions as a Brownian ratchet.
We show that the ribosome generates ~13 pN of force, barely sufficient to unwind
the most stable structures in mRNAs, thus providing a basis for their regulatory
role. Our assay opens the way to characterizing the ribosome's full mechano
chemical cycle.
PMID- 25114096
TI - Elucidation of primary metabolic pathways in Aspergillus species: orphaned
research in characterizing orphan genes.
AB - Primary metabolism affects all phenotypical traits of filamentous fungi.
Particular examples include reacting to extracellular stimuli, producing
precursor molecules required for cell division and morphological changes as well
as providing monomer building blocks for production of secondary metabolites and
extracellular enzymes. In this review, all annotated genes from four Aspergillus
species have been examined. In this process, it becomes evident that 80-96% of
the genes (depending on the species) are still without verified function. A
significant proportion of the genes with verified metabolic functions are
assigned to secondary or extracellular metabolism, leaving only 2-4% of the
annotated genes within primary metabolism. It is clear that primary metabolism
has not received the same attention in the post-genomic area as many other
research areas--despite its role at the very centre of cellular function.
However, several methods can be employed to use the metabolic networks in tandem
with comparative genomics to accelerate functional assignment of genes in primary
metabolism. In particular, gaps in metabolic pathways can be used to assign
functions to orphan genes. In this review, applications of this from the
Aspergillus genes will be examined, and it is proposed that, where feasible, this
should be a standard part of functional annotation of fungal genomes.
PMID- 25114099
TI - Co-author responsibility: Distinguishing between the moral and epistemic aspects
of trust.
PMID- 25114097
TI - Adipose stromal cells differentiate along a smooth muscle lineage pathway upon
endothelial cell contact via induction of activin A.
AB - RATIONALE: Adipose stromal cells (ASC) are therapeutically potent progenitor
cells that possess properties of pericytes. In vivo, ASC in combination with
endothelial cells (EC) establish functional multilayer vessels, in which ASC form
the outer vessel layer and differentiate into mural cells. OBJECTIVE: To identify
factors responsible for ASC differentiation toward the smooth muscle cell
phenotype via interaction with EC. METHODS AND RESULTS: An in vitro model of EC
cocultivation with ASC was used, in which EC organized into vascular cords,
accompanied by ASC migration toward EC and upregulation of alpha-smooth muscle
actin, SM22alpha, and calponin expression. Conditioned media from EC-ASC, but not
from EC cultures, induced smooth muscle cell protein expression in ASC
monocultures. EC-ASC cocultivation induced marked accumulation of activin A but
not transforming growth factor-beta1 in conditioned media. This was attributed to
induction of activin A expression in ASC on contact with EC. Although
transforming growth factor-beta and activin A were individually sufficient to
initiate expression of smooth muscle cell antigens in ASC, only activin A IgG
blocked the effect of EC-ASC conditioned media. Although transforming growth
factor-beta was able to induce activin A expression in ASC, in cocultures this
induction was transforming growth factor-beta independent. In EC-ASC cocultures,
activin A IgG or ALK4/5/7 receptor inhibitors blocked expression of alpha-smooth
muscle actin in ASC in the absence of direct EC-cord contact, but this inhibition
was circumvented in ASC by direct EC contact. CONCLUSIONS: EC initiate a smooth
muscle cell differentiation program in adjacent ASC and propagate this
differentiation in distant ASC by induction of activin A expression.
PMID- 25114098
TI - Epigenetic modification at Notch responsive promoters blunts efficacy of inducing
notch pathway reactivation after myocardial infarction.
AB - RATIONALE: The Notch pathway plays a key role in stimulating mammalian
cardiomyocyte proliferation during development and in the early postnatal life;
in adult zebrafish, reactivation of this pathway is also essential to drive
cardiac regeneration after injury. OBJECTIVE: We wanted to assess efficacy of
Notch pathway stimulation in neonatal and adult hearts as a means to induce
cardiac regeneration after myocardial infarction in mice. METHODS AND RESULTS: In
early postnatal life, cardiomyocyte exit from the cell cycle was paralleled by
decreased Notch signaling and the establishment of a repressive chromatin
environment at Notch-responsive genes, characterized by recruitment of the
polycomb group enhancer of zeste homolog 2 methyltransferase and the acquisition
of the histone 3 Lysine 27 trimethylation histone mark, as detected by chromatin
immunoprecipitation. Forced Notch pathway activation by adenoassociated virus
gene transfer of activated Notch1 or its ligand Jagged1 expanded the
proliferative capacity of neonatal cardiomyocytes; this correlated with increased
transcription of Notch target genes and maintenance of an open chromatin
conformation at their promoters. The same adenoassociated virus vectors, however,
were largely ineffective in stimulating cardiac repair after myocardial
infarction in adult mice, despite optimal and long-lasting transgene expression.
Analysis of Notch-responsive promoters in adult cardiomyocytes showed marks of
repressed chromatin and irreversible CpG DNA methylation. Induction of adult
cardiomyocyte re-entry into the cell cycle with microRNAs was independent from
Notch pathway reactivation. CONCLUSIONS: Notch pathway activation is crucial in
regulating cardiomyocyte proliferation during the early postnatal life, but it is
largely ineffective in driving cardiac regeneration in adults, because of
permanent epigenetic modification at Notch-responsive promoters.
PMID- 25114100
TI - Hepatocyte growth factor limits autoimmune neuroinflammation via glucocorticoid
induced leucine zipper expression in dendritic cells.
AB - Autoimmune neuroinflammation, including multiple sclerosis and its animal model,
experimental autoimmune encephalomyelitis (EAE), a prototype for T cell-mediated
autoimmunity, is believed to result from immune tolerance dysfunction leading to
demyelination and substantial neurodegeneration. We previously showed that CNS
restricted expression of hepatocyte growth factor (HGF), a potent neuroprotective
factor, reduced CNS inflammation and clinical deficits associated with EAE. In
this study, we demonstrate that systemic HGF treatment ameliorates EAE through
the development of tolerogenic dendritic cells (DCs) with high expression levels
of glucocorticoid-induced leucine zipper (GILZ), a transcriptional repressor of
gene expression and a key endogenous regulator of the inflammatory response. RNA
interference-directed neutralization of GILZ expression by DCs suppressed the
induction of tolerance caused by HGF. Finally, adoptive transfer of HGF-treated
DCs from wild-type but not GILZ gene-deficient mice potently mediated functional
recovery in recipient mice with established EAE through effective modulation of
autoaggressive T cell responses. Altogether, these results show that by inducing
GILZ in DCs, HGF reproduces the mechanism of immune regulation induced by potent
immunomodulatory factors such as IL-10, TGF-beta1, and glucocorticoids and
therefore that HGF therapy may have potential in the treatment of autoimmune
dysfunctions.
PMID- 25114101
TI - Innate immune cell CD45 regulates lymphopenia-induced T cell proliferation.
AB - The leukocyte-specific tyrosine phosphatase, CD45, severely impacts T cell
development and activation by modulating TCR signaling. CD45-deficient (CD45KO)
mice have reduced peripheral T cell numbers where CD8 T cells are
underrepresented. In this article, we show that CD45KO mice are unable to support
efficient homeostatic proliferation, affecting CD8 T cells more than CD4 T cells.
Using CD45-RAG1 double-deficient (45RAGKO) mice, we show that lymphopenia-induced
proliferation (LIP) of CD45-sufficient T cells is defective in a host environment
lacking CD45 on innate immune cells. We identify two deficiencies in the 45RAGKO
mice that affect LIP. One involves CD11c(+) cells and the second the production
of IL-7 by lymphoid stromal cells. CD45KO dendritic cells were not defective in
foreign Ag-induced T cell proliferation, yet CD45KO CD11c(+) cells were unable to
rescue the spontaneous LIP in the 45RAGKO mice. This was in contrast with the
CD45-sufficient CD11c(+) cells that partially rescued this spontaneous
proliferation and did so without affecting IL-7 levels. The absence of CD45 also
led to reduced IL-7 production by lymphoid stromal cells, suggesting an indirect
effect of CD45 on innate immune cells in influencing IL-7 production by lymphoid
stromal cells. These findings demonstrate a novel role for CD45 on innate immune
cells in promoting lymphopenia-induced T cell proliferation and suggest that
innate immune cells may communicate with stromal cells to regulate IL-7
production.
PMID- 25114102
TI - Chlamydia trachomatis inhibits inducible NO synthase in human mesenchymal stem
cells by stimulating polyamine synthesis.
AB - Chlamydia trachomatis is considered the most common agent of sexually transmitted
disease worldwide. As an obligate intracellular bacterium, it relies on the host
for survival. Production of NO is an effective antimicrobial defense mechanism of
the innate immune system. However, whether NO is able to arrest chlamydial growth
remains unclear. Similarly, little is known about the mechanisms underlying
subversion of cellular innate immunity by C. trachomatis. By analyzing protein
and mRNA expression in infected human mesenchymal stem cells, combined with RNA
interference and biochemical assays, we observed that infection with C.
trachomatis led to downregulated expression of inducible NO synthase (iNOS) in
human mesenchymal stem cells in vitro. Furthermore, infection upregulated the
expression of the rate-limiting enzyme in the polyamine biosynthetic pathway,
ornithine decarboxylase, diverting the iNOS substrate l-arginine toward the
synthesis of polyamines. Inhibition of ornithine decarboxylase activity using
small interfering RNA or the competitive inhibitor difluoromethylornithine
restored iNOS protein expression and activity in infected cells and inhibited
chlamydial growth. This inhibition was mediated through tyrosine nitration of
chlamydial protein by peroxynitrite, an NO metabolite. Thus, Chlamydia evades
innate immunity by inhibiting NO production through induction of the alternative
polyamine pathway.
PMID- 25114105
TI - The proto-MHC of placozoans, a region specialized in cellular stress and
ubiquitination/proteasome pathways.
AB - The MHC is a large genetic region controlling Ag processing and recognition by T
lymphocytes in vertebrates. Approximately 40% of its genes are implicated in
innate or adaptive immunity. A putative proto-MHC exists in the chordate
amphioxus and in the fruit fly, indicating that a core MHC region predated the
emergence of the adaptive immune system in vertebrates. In this study, we
identify a putative proto-MHC with archetypal markers in the most basal branch of
Metazoans--the placozoan Trichoplax adhaerens, indicating that the proto-MHC is
much older than previously believed--and present in the common ancestor of
bilaterians (contains vertebrates) and placozoans. Our evidence for a T.
adhaerens proto-MHC was based on macrosynteny and phylogenetic analyses revealing
approximately one third of the multiple marker sets within the human MHC-related
paralogy groups have unique counterparts in T. adhaerens, consistent with two
successive whole genome duplications during early vertebrate evolution. A genetic
ontologic analysis of the proto-MHC markers in T. adhaerens was consistent with
its involvement in defense, showing proteins implicated in antiviral immunity,
stress response, and ubiquitination/proteasome pathway. Proteasome genes psma,
psmb, and psmd are present, whereas the typical markers of adaptive immunity,
such as MHC class I and II, are absent. Our results suggest that the proto-MHC
was involved in intracellular intrinsic immunity and provide insight into the
primordial architecture and functional landscape of this region that later in
evolution became associated with numerous genes critical for adaptive immunity in
vertebrates.
PMID- 25114103
TI - Peptidoglycan recognition protein 3 and Nod2 synergistically protect mice from
dextran sodium sulfate-induced colitis.
AB - Aberrant immune response and changes in the gut microflora are the main causes of
inflammatory bowel disease (IBD). Peptidoglycan recognition proteins (Pglyrp1,
Pglyrp2, Pglyrp3, and Pglyrp4) are bactericidal innate immunity proteins that
maintain normal gut microbiome, protect against experimental colitis, and are
associated with IBD in humans. Nucleotide-binding oligomerization domain 2 (Nod2)
is an intracellular bacterial sensor and may be required for maintaining normal
gut microbiome. Mutations in Nod2 are strongly associated with Crohn's disease,
but the causative mechanism is not understood, and the role of Nod2 in ulcerative
colitis is not known. Because IBD is likely caused by variable multiple mutations
in different individuals, in this study, we examined the combined role of Pglyrp3
and Nod2 in the development of experimental colitis in mice. We demonstrate that
a combined deficiency of Pglyrp3 and Nod2 results in higher sensitivity to
dextran sodium sulfate-induced colitis compared with a single deficiency.
Pglyrp3(-/-)Nod2(-/-) mice had decreased survival and higher loss of body weight,
increased intestinal bleeding, higher apoptosis of colonic mucosa, elevated
expression of cytokines and chemokines, altered gut microbiome, and increased
levels of ATP in the colon. Increased sensitivity to dextran sodium sulfate
induced colitis in Pglyrp3(-/-)Nod2(-/-) mice depended on increased apoptosis of
intestinal epithelium, changed gut microflora, and elevated ATP. Pglyrp3
deficiency contributed colitis-predisposing intestinal microflora and increased
intestinal ATP, whereas Nod2 deficiency contributed higher apoptosis and
responsiveness to increased level of ATP. In summary, Pglyrp3 and Nod2 are both
required for maintaining gut homeostasis and protection against colitis, but
their protective mechanisms differ.
PMID- 25114106
TI - 6-Methoxyflavone inhibits NFAT translocation into the nucleus and suppresses T
cell activation.
AB - NFAT plays a crucial role in the immune system by regulating the transcription of
inducible genes during immune responses. In T cells, NFAT proteins govern various
cellular events related to T cell development, activation, tolerance induction,
and differentiation. We previously reported the NFAT1-dependent enhancer activity
of conserved noncoding sequence (CNS)-9, a distal cis-acting element, in the
regulation of IL-10 transcription in T cells. In this study, we developed a T
cell-based reporter system to identify compounds that modulate the regulatory
activity of CNS-9. Among the identified candidates, 6-methoxyflavone (6-MF)
significantly inhibited the enhancer activity of CNS-9, thereby reducing IL-10
expression in T cells without affecting cell viability. 6-MF also downregulated
the transcription of NFAT1 target genes such as IL-4, IL-13, and IFN-gamma.
Treatment of 6-MF inhibited the translocation of NFAT1 into the nucleus, which
consequently interrupted NFAT1 binding to the target loci, without affecting the
expression or dephosphorylation of NFAT1. Treatment of 6-MF to CD4(+) T cells or
B cells isolated from mice with atopic dermatitis significantly reduced disease
associated cytokine production, as well as the levels of IgE. In addition, oral
administration of 6-MF to atopic dermatitis mice ameliorated disease symptoms by
reducing serum IgE levels and infiltrating lymphocytes. Conclusively, our results
suggest that 6-MF can be a potential candidate for the development of an
effective immunomodulator via the suppression of NFAT-mediated T cell activation.
PMID- 25114104
TI - MyD88 signaling inhibits protective immunity to the gastrointestinal helminth
parasite Heligmosomoides polygyrus.
AB - Helminth parasites remain one of the most common causes of infections worldwide,
yet little is still known about the immune signaling pathways that control their
expulsion. C57BL/6 mice are chronically susceptible to infection with the
gastrointestinal helminth parasite Heligmosomoides polygyrus. In this article, we
report that C57BL/6 mice lacking the adapter protein MyD88, which mediates
signaling by TLRs and IL-1 family members, showed enhanced immunity to H.
polygyrus infection. Alongside increased parasite expulsion, MyD88-deficient mice
showed heightened IL-4 and IL-17A production from mesenteric lymph node CD4(+)
cells. In addition, MyD88(-/-) mice developed substantial numbers of intestinal
granulomas around the site of infection, which were not seen in MyD88-sufficient
C57BL/6 mice, nor when signaling through the adapter protein TRIF (TIR domain
containing adapter-inducing IFN-beta adapter protein) was also ablated. Mice
deficient solely in TLR2, TLR4, TLR5, or TLR9 did not show enhanced parasite
expulsion, suggesting that these TLRs signal redundantly to maintain H. polygyrus
susceptibility in wild-type mice. To further investigate signaling pathways that
are MyD88 dependent, we infected IL-1R1(-/-) mice with H. polygyrus. This
genotype displayed heightened granuloma numbers compared with wild-type mice, but
without increased parasite expulsion. Thus, the IL-1R-MyD88 pathway is implicated
in inhibiting granuloma formation; however, protective immunity in MyD88
deficient mice appears to be granuloma independent. Like IL-1R1(-/-) and MyD88(-/
) mice, animals lacking signaling through the type 1 IFN receptor (i.e., IFNAR1(
/-)) also developed intestinal granulomas. Hence, IL-1R1, MyD88, and type 1 IFN
receptor signaling may provide pathways to impede granuloma formation in vivo,
but additional MyD88-mediated signals are associated with inhibition of
protective immunity in susceptible C57BL/6 mice.
PMID- 25114107
TI - Prevention of neutrophil extravasation by alpha2-adrenoceptor-mediated
endothelial stabilization.
AB - Adrenergic receptors are expressed on the surface of inflammation-mediating
cells, but their potential role in the regulation of the inflammatory response is
still poorly understood. The objectives of this work were to study the effects of
alpha2-adrenergic agonists on the inflammatory response in vivo and to determine
their mechanism of action. In two mouse models of inflammation, zymosan air pouch
and thioglycolate-induced peritonitis models, the i.m. treatment with xylazine or
UK14304, two alpha2-adrenergic agonists, reduced neutrophil migration by 60%. The
alpha2-adrenergic antagonist RX821002 abrogated this effect. In flow cytometry
experiments, the basal surface expression of L-selectin and CD11b was modified
neither in murine nor in human neutrophils upon alpha2-agonist treatment. Similar
experiments in HUVEC showed that UK14304 prevented the activation-dependent
upregulation of ICAM-1. In contrast, UK14304 augmented electrical resistance and
reduced macromolecular transport through a confluent HUVEC monolayer. In flow
chamber experiments, under postcapillary venule-like flow conditions, the
pretreatment of HUVECs, but not neutrophils, with alpha2-agonists decreased
transendothelial migration, without affecting neutrophil rolling. Interestingly,
alpha2-agonists prevented the TNF-alpha-mediated decrease in expression of the
adherens junctional molecules, VE-cadherin, beta-catenin, and plakoglobin, and
reduced the ICAM-1-mediated phosphorylation of VE-cadherin by immunofluorescence
and confocal analysis and Western blot analysis, respectively. These findings
indicate that alpha2-adrenoceptors trigger signals that protect the integrity of
endothelial adherens junctions during the inflammatory response, thus pointing at
the vascular endothelium as a therapeutic target for the management of
inflammatory processes in humans.
PMID- 25114108
TI - Glycosylation and immunoreactivity of the Histoplasma capsulatum Cfp4 yeast-phase
exoantigen.
AB - The yeast phase of Histoplasma capsulatum is the virulent form of this thermally
dimorphic fungal pathogen. Among the secreted proteome of Histoplasma, culture
filtrate protein 4 (Cfp4) is a heavily glycosylated factor produced abundantly
and specifically by Histoplasma yeast cells, suggesting its role in pathogenesis.
We have generated three monoclonal antibodies as tools for characterization and
detection of Cfp4 and determined the epitope each recognizes. Through site
directed mutagenesis of Cfp4, we identified three asparagines that function as
the principal sites of N-linked glycan modification. To test the function of Cfp4
in Histoplasma pathogenesis, we generated Cfp4-deficient strains by insertional
mutagenesis and by RNA interference. Cfp4-deficient strains are not attenuated in
virulence in human macrophages or during lung infection in a murine model of
histoplasmosis. Coinfection of differentially marked Cfp4-producing and Cfp4
deficient strains demonstrates that production of Cfp4 does not confer a fitness
advantage to Histoplasma yeasts during murine lung infection. Despite no apparent
role in acute virulence in mice, secretion of the Cfp4 glycoprotein by yeast
cells is consistent across clinical and laboratory isolates of the North American
type 1 and type 2 phylogenetic groups as well as a strain from Panama. In
addition, human immune sera recognize the Histoplasma Cfp4 protein, confirming
Cfp4 production during infection of human hosts. These results suggest the
potential utility of Cfp4 as a diagnostic exoantigen for histoplasmosis.
PMID- 25114111
TI - Tick passage results in enhanced attenuation of Babesia bovis.
AB - Serial blood passage of virulent Babesia bovis in splenectomized cattle results
in attenuated derivatives that do not cause neurologic disease. Tick
transmissibility can be lost with attenuation, but when retained, attenuated B.
bovis can revert to virulence following tick passage. This study provides data
showing that tick passage of the partially attenuated B. bovis T2Bo derivative
strain further decreased virulence compared with intravenous inoculation of the
same strain in infected animals. Ticks that acquired virulent or attenuated
parasites by feeding on infected cattle were transmission fed on naive,
splenectomized animals. While there was no significant difference between groups
in the number of parasites in the midgut, hemolymph, or eggs of replete female
ticks after acquisition feeding, animals infected with the attenuated parasites
after tick transmission showed no clinical signs of babesiosis, unlike those
receiving intravenous challenge with the same attenuated strain prior to tick
passage. Additionally, there were significantly fewer parasites in blood and
tissues of animals infected with tick-passaged attenuated parasites. Sequencing
analysis of select B. bovis genes before and after tick passage showed
significant differences in parasite genotypes in both peripheral blood and
cerebral samples. These results provide evidence that not only is tick
transmissibility retained by the attenuated T2Bo strain, but also it results in
enhanced attenuation and is accompanied by expansion of parasite subpopulations
during tick passage that may be associated with the change in disease phenotype.
PMID- 25114110
TI - Masking of beta(1-3)-glucan in the cell wall of Candida albicans from detection
by innate immune cells depends on phosphatidylserine.
AB - The virulence of Candida albicans in a mouse model of invasive candidiasis is
dependent on the phospholipids phosphatidylserine (PS) and
phosphatidylethanolamine (PE). Disruption of the PS synthase gene CHO1 (i.e.,
cho1Delta/Delta) eliminates PS and blocks the de novo pathway for PE
biosynthesis. In addition, the cho1Delta/Delta mutant's ability to cause invasive
disease is severely compromised. The cho1Delta/Delta mutant also exhibits cell
wall defects, and in this study, it was determined that loss of PS results in
decreased masking of cell wall beta(1-3)-glucan from the immune system. In wild
type C. albicans, the outer mannan layer of the wall masks the inner layer of
beta(1-3)-glucan from exposure and detection by innate immune effector molecules
like the C-type signaling lectin Dectin-1, which is found on macrophages,
neutrophils, and dendritic cells. The cho1Delta/Delta mutant exhibits increases
in exposure of beta(1-3)-glucan, which leads to greater binding by Dectin-1 in
both yeast and hyphal forms. The unmasking of beta(1-3)-glucan also results in
increased elicitation of TNF-alpha from macrophages in a Dectin-1-dependent
manner. The role of phospholipids in fungal pathogenesis is an emerging field,
and this is the first study showing that loss of PS in C. albicans results in
decreased masking of beta(1-3)-glucan, which may contribute to our understanding
of fungus-host interactions.
PMID- 25114109
TI - LcrV delivered via type III secretion system of live attenuated Yersinia
pseudotuberculosis enhances immunogenicity against pneumonic plague.
AB - Here, we constructed a Yersinia pseudotuberculosis mutant strain with arabinose
dependent regulated and delayed shutoff of crp expression (araC P(BAD) crp) and
replacement of the msbB gene with the Escherichia coli msbB gene to attenuate it.
Then, we inserted the asd mutation into this construction to form chi10057
[Deltaasd-206 DeltamsbB868::P(msbB) msbB(EC) DeltaP(crp21)::TT araC P(BAD) crp]
for use with a balanced-lethal Asd-positive (Asd(+)) plasmid to facilitate
antigen synthesis. A hybrid protein composed of YopE (amino acids [aa]1 to 138)
fused with full-length LcrV (YopE(Nt138)-LcrV) was synthesized in chi10057
harboring an Asd(+) plasmid (pYA5199, yopE(Nt138)-lcrV) and could be secreted
through a type III secretion system (T3SS) in vitro and in vivo. Animal studies
indicated that mice orally immunized with chi10057(pYA5199) developed titers of
IgG response to whole-cell lysates of Y. pestis (YpL) and subunit LcrV similar to
those seen with chi10057(pYA3332) (chi10057 plus an empty plasmid). However, only
immunization of mice with chi10057(pYA5199) resulted in a significant secretory
IgA response to LcrV. chi10057(pYA5199) induced a higher level of protection (80%
survival) against intranasal (i.n.) challenge with ~240 median lethal doses
(LD50) (2.4 * 10(4) CFU) of Y. pestis KIM6+(pCD1Ap) than chi10057(pYA3332) (40%
survival). Splenocytes from mice vaccinated with chi10057(pYA5199) produced
significant levels of gamma interferon (IFN-gamma), tumor necrosis factor alpha
(TNF-alpha), and interleukin-17 (IL-17) after restimulation with LcrV and YpL
antigens. Our results suggest that it is possible to use an attenuated Y.
pseudotuberculosis strain delivering the LcrV antigen via the T3SS as a potential
vaccine candidate against pneumonic plague.
PMID- 25114112
TI - The serine/threonine kinase STK11 promotes Shigella flexneri dissemination
through establishment of cell-cell contacts competent for tyrosine kinase
signaling.
AB - Shigella flexneri is an intracellular pathogen that disseminates in the
intestinal epithelium by displaying actin-based motility. We found that although
S. flexneri displayed comparable actin-based motilities in the cytosols of
HeLa229 and HT-29 epithelial cell lines, the overall dissemination process was
much more efficient in HT-29 cells. Time-lapse microscopy demonstrated that as
motile bacteria reached the cell cortex in HT-29 cells, they formed membrane
protrusions that resolved into vacuoles, from which the bacteria escaped and
gained access to the cytosol of adjacent cells. In HeLa229 cells, S. flexneri
also formed membrane protrusions that extended into adjacent cells, but the
protrusions rarely resolved into vacuoles. Instead, the formed protrusions
collapsed and retracted, bringing the bacteria back to the cytosol of the primary
infected cells. Silencing the serine/threonine kinase STK11 (also known as LKB1)
in HT-29 cells decreased the efficiency of protrusion resolution into vacuoles.
Conversely, expressing STK11 in HeLa229 cells, which lack the STK11 locus,
dramatically increased the efficiency of protrusion resolution into vacuoles. S.
flexneri dissemination in HT-29 cells led to the local phosphorylation of
tyrosine residues in protrusions, a signaling event that was not observed in
HeLa229 cells but was restored in STK11-expressing HeLa229 cells. Treatment of HT
29 cells with the tyrosine kinase inhibitor imatinib abrogated tyrosine kinase
signaling in protrusions, which correlated with a severe decrease in the
efficiency of protrusion resolution into vacuoles. We suggest that the formation
of STK11-dependent lateral cell-cell contacts competent for tyrosine kinase
signaling promotes S. flexneri dissemination in epithelial cells.
PMID- 25114113
TI - Epithelial innate immune response to Acinetobacter baumannii challenge.
AB - Currently, Acinetobacter baumannii is recognized as one of the major pathogens
seriously threatening our health care delivery system. Aspects of the innate
immune response to A. baumannii infection are not yet well understood. Human beta
defensins (hBDs) are epithelial cell-derived cationic antimicrobial peptides
(AMPs) that also function to bridge the innate and adaptive immune system. We
tested the induction of hBD-2 and -3 by A. baumannii on primary oral and skin
epithelial cells and found that A. baumannii induces hBD-3 transcripts to a
greater extent than it induces hBD-2 transcripts on both types of cells. In
addition, we found that A. baumannii is susceptible to hBD-2 and -3 killing at
submicromolar concentrations. Moreover, hBD-3 induction by A. baumannii was found
to be dependent on epidermal growth factor receptor (EGFR) signaling. Inhibition
of mitogen-activated protein kinase resulted in reduced expression of both hBD-2
and -3. Lastly, a disintegrin and metalloprotease 17 (ADAM17; also known as TACE)
was found to be critical for hBD-3 induction, while ADAM10 and dual oxidase 1
(Duox1) were not required for hBD-3 induction. Induction of AMPs is an important
component of innate sensing of pathogens and may play an important role in
triggering systemic immune responses to A. baumannii infection. Further studies
on the interactions between epithelial cells and A. baumannii will help us
understand early stages of infection and may shed light on why some individuals
are more vulnerable to A. baumannii infection.
PMID- 25114114
TI - BDCA1-positive dendritic cells (DCs) represent a unique human myeloid DC subset
that induces innate and adaptive immune responses to Staphylococcus aureus
Infection.
AB - Staphylococcus aureus bloodstream infection (bacteremia) is a major cause of
morbidity and mortality and places substantial cost burdens on health care
systems. The role of peripheral blood dendritic cells (PBDCs) in the immune
responses against S. aureus infection has not been well characterized. In this
study, we demonstrated that BDCA1(+) myeloid DCs (mDCs) represent a unique PBDC
subset that can induce immune responses against S. aureus infection. BDCA1(+)
mDCs could engulf S. aureus and strongly upregulated the expression of
costimulatory molecules and production of proinflammatory cytokines. Furthermore,
BDCA1(+) mDCs expressed high levels of major histocompatibility complex (MHC)
class I and II molecules in response to S. aureus and greatly promoted
proliferation and gamma interferon (IFN-gamma) production in CD4 and CD8 T cells.
Moreover, BDCA1(+) mDCs expressed higher levels of Toll-like receptor 2 (TLR-2)
and scavenger receptor A (SR-A) than those on CD16(+) and BDCA3(+) mDCs, and
these two receptors were both required for the recognition of S. aureus and the
subsequent activation of BDCA1(+) mDCs. Finally, BDCA1(+) mDC-mediated immune
responses against S. aureus were dependent on MyD88 signaling pathways. These
results demonstrate that human BDCA1(+) mDCs represent a unique subset of mDCs
that can respond to S. aureus to undergo maturation and activation and to induce
Th1 and Tc1 immune responses.
PMID- 25114116
TI - Blockade of indoleamine 2,3-dioxygenase reduces mortality from peritonitis and
sepsis in mice by regulating functions of CD11b+ peritoneal cells.
AB - Indoleamine 2,3-dioxygenase-1 (Ido), which catalyzes the first and limiting step
of tryptophan catabolism, has been implicated in immune tolerance. However, the
roles of Ido in systemic bacterial infection are complicated and remain
controversial. To explore this issue, we examined the roles of Ido in bacterial
peritonitis and sepsis after cecal ligation and puncture (CLP) in mice by using
the Ido inhibitor 1-methyl-d,l-tryptophan (1-MT), by comparing Ido(+/+) and Ido(
/-) mice, or by using chimeric mice in which Ido in the bone marrow-derived cells
was deficient. Ido expression in the peritoneal CD11b(+) cells and its metabolite
l-kynurenine in the serum were increased after CLP. 1-MT treatment or Ido
deficiency, especially in bone marrow-derived cells, reduced mortality after CLP.
Compared to Ido(+/+) mice, Ido(-/-) mice showed increased recruitment of
neutrophils and mononuclear cells into the peritoneal cavity and a decreased
bacterial count in the blood accompanied by increased CXCL-2 and CXCL-1 mRNA in
the peritoneal cells. Ido has an inhibitory effect on LPS-induced CXCL-2 and CXCL
1 production in cultured peritoneal cells. These findings indicate that
inhibition of Ido reduces mortality from peritonitis and sepsis after CLP via
recruitment of neutrophils and mononuclear cells by chemokine production in
peritoneal CD11b(+) cells. Thus, blockade of Ido plays a beneficial role in host
protection during bacterial peritonitis and sepsis.
PMID- 25114115
TI - New insights into the antimicrobial effect of mast cells against Enterococcus
faecalis.
AB - Enterococcus faecalis has emerged as an important cause of life-threatening
multidrug-resistant bacterial infections in the hospital setting. The
pathogenesis of enterococcal infections has remained a relatively neglected field
despite their obvious clinical relevance. The objective of this study was to
characterize the interactions between mast cells (MCs), an innate immune cell
population abundant in the intestinal lamina propria, and E. faecalis. This study
was conducted with primary bone marrow-derived murine MCs. The results
demonstrated that MCs exerted an antimicrobial effect against E. faecalis that
was mediated both by degranulation, with the concomitant discharge of the
antimicrobial effectors contained in the granules, and by the release of
extracellular traps, in which E. faecalis was snared and killed. In particular,
the cathelicidin LL-37 released by the MCs had potent antimicrobial effect
against E. faecalis. We also investigated the specific receptors involved in the
recognition of E. faecalis by MCs. We found that Toll-like receptors (TLRs) are
critically involved in the MC recognition of E. faecalis, since MCs deficient in
the expression of MyD88, an adaptor molecule required for signaling by most TLRs,
were significantly impaired in their capacity to degranulate, to reduce E.
faecalis growth as well as to release tumor necrosis factor alpha (TNF-alpha) and
interleukin 6 (IL-6) after encountering this pathogen. Furthermore, TLR2 was
identified as the most prominent TLR involved in the recognition of E. faecalis
by MCs. The results of this study indicate that MCs may be important contributors
to the host innate immune defenses against E. faecalis.
PMID- 25114117
TI - The interleukin-1beta/CXCL1/2/neutrophil axis mediates host protection against
group B streptococcal infection.
AB - Previous studies have indicated that group B streptococcus (GBS), a frequent
human pathogen, potently induces the release of interleukin-1beta (IL-1beta), an
important mediator of inflammatory responses. Since little is known about the
role of this cytokine in GBS disease, we analyzed the outcome of infection in IL
1beta-deficient mice. These animals were markedly sensitive to GBS infection,
with most of them dying under challenge conditions that caused no deaths in wild
type control mice. Lethality was due to the inability of the IL-1beta-deficient
mice to control local GBS replication and dissemination to target organs, such as
the brain and the kidneys. Moreover, in a model of inflammation induced by the
intraperitoneal injection of killed GBS, a lack of IL-1beta was associated with
selective impairment in the production of the neutrophil chemokines CXCL1 and
CXCL2 and in neutrophil recruitment to the peritoneal cavity. Decreased blood
neutrophil counts and impaired neutrophil recruitment to the brain and kidneys
were also observed during GBS infection in IL-1beta-deficient mice concomitantly
with a reduction in CXCL1 and CXCL2 tissue levels. Notably, the
hypersusceptibility to GBS infection observed in the immune-deficient animals was
recapitulated by neutrophil depletion with anti-Gr1 antibodies. Collectively, our
data identify a cytokine circuit that involves IL-1beta-induced production of
CXCL1 and CXCL2 and leads the recruitment of neutrophils to GBS infection sites.
Moreover, our data point to an essential role of these cells in controlling the
progression and outcome of GBS disease.
PMID- 25114119
TI - Characterization of a lipopolysaccharide-targeted monoclonal antibody and its
variable fragments as candidates for prophylaxis against the obligate
intracellular bacterial pathogen Coxiella burnetii.
AB - Our previous study demonstrated that treatment of Coxiella burnetii with the
phase I lipopolysaccharide (PI-LPS)-targeted monoclonal antibody (MAb) 1E4
significantly inhibited C. burnetii infection in mice, suggesting that 1E4 is a
protective MAb. To determine whether passive transfer of antibodies (Abs) can
provide protection against C. burnetii natural infection, we examined if passive
transfer of 1E4 would protect SCID mice against C. burnetii aerosol infection.
The results indicated that 1E4 conferred significant protection against
aerosolized C. burnetii, suggesting that 1E4 may be useful for preventing C.
burnetii natural infection. To further understand the mechanisms of 1E4-mediated
protection and to test the possibility of using humanized 1E4 to prevent C.
burnetii infection, we examined whether the Fab fragment of 1E4 (Fab1E4), a
recombinant murine single-chain variable fragment (muscFv1E4), and a humanized
single-chain variable fragment (huscFv1E4) retained the ability of 1E4 to inhibit
C. burnetii infection. The results indicated that Fab1E4, muscFv1E4, and
huscFv1E4 were able to inhibit C. burnetii infection in mice but that their
ability to inhibit C. burnetii infection was lower than that of 1E4. In addition,
treatment of C. burnetii with Fab1E4, muscFv1E4, or huscFv1E4 can block C.
burnetii infection of macrophages. Interestingly, treatment of C. burnetii with
huscFv1E4 can significantly reduce C. burnetii infectivity in human macrophages.
This report provides the first evidence to demonstrate that the humanized
variable fragments of an LPS-specific MAb can neutralize C. burnetii infection
and appears to be a promising step toward the potential use of a humanized MAb as
emergency prophylaxis against C. burnetii exposure.
PMID- 25114121
TI - Human monocyte subsets at homeostasis and their perturbation in numbers and
function in filarial infection.
AB - To characterize the function and plasticity of the major human circulating
monocyte populations and to explore their role in systemic helminth infection,
highly purified (by flow-based sorting) human monocyte subsets
(CD14(hi)/CD16(neg) [classical], CD14(+ or hi)/CD16(med) [intermediate], and
CD14(neg)/CD16(hi) [nonclassical]) were examined at homeostasis and after
activation. Among these three subsets the classical and intermediate subsets were
found to be the major sources of inflammatory and regulatory cytokines, as well
as cytokines/chemokines associated with alternative activation, whereas the
nonclassical and classical populations demonstrated an ability to transmigrate
through endothelial monolayers. Moreover, it was primarily the classical subset
that was the most efficient in promoting autologous T cell proliferation. The
distribution of these subsets changed in the context of a systemic helminth
(Wuchereria bancrofti) infection such that patent infection altered the frequency
and distribution of these monocyte subsets with the nonclassical monocytes being
expanded (almost 2-fold) in filarial infection. To understand further the
filarial/monocyte interface, in vitro modeling demonstrated that the classical
subset internalized filarial antigens more efficiently than the other two subsets
but that the parasite-driven regulatory cytokine interleukin-10 was exclusively
coming from the intermediate subset. Our data suggest that monocyte subsets have
a differential function at homeostasis and in response to helminth parasites.
PMID- 25114118
TI - Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the
lungs of cystic fibrosis patients.
AB - Cystic fibrosis (CF) patients have increased susceptibility to chronic lung
infections by Pseudomonas aeruginosa, but the ecophysiology within the CF lung
during infections is poorly understood. The aim of this study was to elucidate
the in vivo growth physiology of P. aeruginosa within lungs of chronically
infected CF patients. A novel, quantitative peptide nucleic acid (PNA)
fluorescence in situ hybridization (PNA-FISH)-based method was used to estimate
the in vivo growth rates of P. aeruginosa directly in lung tissue samples from CF
patients and the growth rates of P. aeruginosa in infected lungs in a mouse
model. The growth rate of P. aeruginosa within CF lungs did not correlate with
the dimensions of bacterial aggregates but showed an inverse correlation to the
concentration of polymorphonuclear leukocytes (PMNs) surrounding the bacteria. A
growth-limiting effect on P. aeruginosa by PMNs was also observed in vitro, where
this limitation was alleviated in the presence of the alternative electron
acceptor nitrate. The finding that P. aeruginosa growth patterns correlate with
the number of surrounding PMNs points to a bacteriostatic effect by PMNs via
their strong O2 consumption, which slows the growth of P. aeruginosa in infected
CF lungs. In support of this, the growth of P. aeruginosa was significantly
higher in the respiratory airways than in the conducting airways of mice. These
results indicate a complex host-pathogen interaction in chronic P. aeruginosa
infection of the CF lung whereby PMNs slow the growth of the bacteria and render
them less susceptible to antibiotic treatment while enabling them to persist by
anaerobic respiration.
PMID- 25114120
TI - Bacterial heterogeneity is a requirement for host superinfection by the Lyme
disease spirochete.
AB - In nature, mixed Borrelia burgdorferi infections are common and possibly can be
acquired by either superinfection or coinfection. Superinfection by heterologous
B. burgdorferi strains has been established experimentally, although the ability
of homologous B. burgdorferi clones to superinfect a host has not been studied in
detail. Information regarding any potential immune barriers to secondary
infection also currently is unavailable. In the present study, the ability to
superinfect various mouse models by homologous wild-type clones was examined and
compared to superinfection by heterologous strains. To assess the ability of
homologous B. burgdorferi clones to successfully superinfect a mouse host,
primary- and secondary-infecting spirochetes were recovered via in vitro
cultivation of collected blood or tissue samples. This was accomplished by
generating two different antibiotic-resistant versions of the wild-type B31-A3
clone in order to distinguish superinfecting B. burgdorferi from primary
infecting spirochetes. The data demonstrate an inability of homologous B.
burgdorferi to superinfect immunocompetent mice as opposed to heterologous
strains. Attempts to superinfect different types of immunodeficient mice with
homologous B. burgdorferi indicate that the murine innate immune system
represents a major barrier to intrastrain superinfection. Consequently, the
possibility of innate immunity as a driving force for B. burgdorferi
heterogeneity during the enzootic cycle is discussed.
PMID- 25114123
TI - Fixed versus removable orthodontic appliances to correct anterior crossbite in
the mixed dentition--a randomized controlled trial.
AB - OBJECTIVE: To compare the effectiveness of fixed and removable orthodontic
appliances in correcting anterior crossbite with functional shift in the mixed
dentition. SUBJECTS AND METHODS: Consecutive recruitment of 64 patients who met
the following inclusion criteria: early to late mixed dentition, anterior
crossbite with functional shift, moderate space deficiency in the maxilla, i.e.
up to 4mm, a non-extraction treatment plan, the ANB angle > 0 degree, and no
previous orthodontic treatment. Sixty-two patients agreed to participate. The
study was designed as a randomized controlled trial with two parallel arms. After
written consent was obtained, the patients were randomized, in blocks of 10, for
treatment either with a removable appliance with protruding springs or a fixed
appliance with multi-brackets. The main outcome measures assessed were success
rate, duration of treatment, and changes in overjet, overbite, and arch length.
The results were also analysed on an intention-to-treat basis. RESULTS: The
crossbite was successfully corrected in all patients in the fixed appliance group
and all except one in the removable appliance group. The average duration of
treatment was significantly less, 1.4 months, for the fixed appliance group (P <
0.05). There were significant increases in arch length and overjet in both
treatment groups, but significantly more in the fixed appliance group (P < 0.05
and P < 0.01). CONCLUSION: Anterior crossbite with functional shift in the mixed
dentition can be successfully corrected by either fixed or removable appliance
therapy in a short-term perspective.
PMID- 25114124
TI - Alveolar bone mapping in subjects with different vertical facial dimensions.
AB - OBJECTIVE: The purpose of this study was to investigate differences in alveolar
and skeletal dimensions among subjects with different vertical facial dimensions
using cone beam computed tomography (CBCT). To date, this is the first study that
investigates the relationship between facial type and posterior alveolar
thickness in both maxilla and mandible, using CBCT data. MATERIALS AND METHODS:
From a sample of 152 CBCT scans, 45 scans were selected to be included in the
study. CBCT-synthesized lateral cephalograms were used to categorize subjects
into three groups based on their vertical skeletal pattern. Using iCATVisionTM
software, measurements of alveolar height and thickness were carried out in the
entire tooth-bearing region. In addition, AutoCADTM software was used to carry
out measurements for the anatomical limitation to labio-lingual incisor movement.
Kruskal-Wallis and Mann-Whitney U-tests with the Bonferroni adjustment were done
for statistical analyses. RESULTS: Compared to the other two groups, high-angle
group had larger anterior dentoalveolar height with no significant differences in
alveolar height posteriorly, in both the maxilla and mandible. Furthermore, high
angle group presented thinner alveolus anteriorly in the maxilla and at almost
all sites in the mandible. Low-angle group had higher mean values for some
measurements of the anatomical limitation to labio-lingual incisor movement for
all upper and lower incisors. LIMITATIONS: Inherent limitations of CBCT scanning
as related to physical spatial resolution of the image and limitations posed by
the study sample size should be considered. CONCLUSIONS: There is a statistically
significant relationship between facial type and alveolar height and thickness.
High-angle subjects can be at increased risk of moving incisors beyond alveolar
bone support when subjected to marked antero-posterior incisor movement.
PMID- 25114122
TI - Role of pathogen-derived cell wall carbohydrates and prostaglandin E2 in immune
response and suppression of fish immunity by the oomycete Saprolegnia parasitica.
AB - Saprolegnia parasitica is a freshwater oomycete that is capable of infecting
several species of fin fish. Saprolegniosis, the disease caused by this microbe,
has a substantial impact on Atlantic salmon aquaculture. No sustainable treatment
against saprolegniosis is available, and little is known regarding the host
response. In this study, we examined the immune response of Atlantic salmon to S.
parasitica infection and to its cell wall carbohydrates. Saprolegnia triggers a
strong inflammatory response in its host (i.e., induction of interleukin-1beta1
[IL-1beta1], IL-6, and tumor necrosis factor alpha), while severely suppressing
the expression of genes associated with adaptive immunity in fish, through
downregulation of T-helper cell cytokines, antigen presentation machinery, and
immunoglobulins. Oomycete cell wall carbohydrates were recognized by fish
leukocytes, triggering upregulation of genes involved in the inflammatory
response, similar to what is observed during infection. Our data suggest that S.
parasitica is capable of producing prostaglandin [corrected] E2 (PGE2) in vitro,
a metabolite not previously shown to be produced by oomycetes, and two proteins
with homology to vertebrate enzymes known to play a role in prostaglandin
biosynthesis have been identified in the oomycete genome. Exogenous PGE2 was
shown to increase the inflammatory response in fish leukocytes incubated with
cell wall carbohydrates while suppressing genes involved in cellular immunity
(gamma interferon [IFN-gamma] and the IFN-gamma-inducible protein [gamma-IP]).
Inhibition of S. parasitica zoospore germination and mycelial growth by two
cyclooxygenase inhibitors (aspirin and indomethacin) also suggests that
prostaglandins may be involved in oomycete development.
PMID- 25114125
TI - Does coronary endarterectomy technique affect surgical outcome when combined with
coronary artery bypass grafting?
AB - A best evidence topic in cardiac surgery was written according to a structured
protocol. The question addressed was whether open coronary endarterectomy (CE)
and coronary artery bypass grafting (CABG) compares favourably with closed
endarterectomy and CABG in the myocardial revascularization of patients
presenting with diffuse coronary artery disease (DCAD). One hundred and fifty
five articles were identified by a systematic search, of which 10 best answered
the clinical question incorporating a total of 1203 patients (915 open-CE, 288
closed-CE). All were observational studies. Two were comparative and the
remaining eight were case series. The authors, journal, date, country of
publication, patient group, study type, relevant outcomes and results were
recorded. The open technique involved removal of atheroma under direct vision
through an arteriotomy along the length of diffusely stenotic artery, whereas the
closed technique involved a smaller arteriotomy and removal via traction on the
proximal plaque. The overall postoperative mortality rate associated with open-CE
ranged from 2.3 to 10.5%. Both comparative studies demonstrated at least
equivalent 30-day mortality between open-CE and closed-CE. Notably, the four
studies with highest overall postoperative mortality used a saphenous vein (SV)
graft in the majority of patients. Furthermore, two-vessel CE was associated with
higher mortality rates. Among these best evidence series, the overall incidence
rate of postoperative myocardial infarction (MI) was 7.3% (88/1203). Whether open
CE or the use of internal thoracic artery (ITA) conduit over SV affects
postoperative MI rates remains inconclusive. Mid-term and long-term graft
patency, and 3-, 4- and 5-year survival rates are all improved when open-CE is
combined with the ITA bypass conduit, when compared with closed-CE or open-CE
using another conduit. In summary, open-CE with CABG in the setting of DCAD may
carry lower 30-day mortality than closed-CE with CABG. Utilization of ITA appears
to improve mortality, whereas the SV conduit and multivessel CE may worsen
clinical outcome. Furthermore, the ITA may also improve graft patency when
combined with open-CE. There is currently insufficient evidence to determine the
effect of open-CE on MI incidence. Future large, prospective studies are now
required with defined subgroups, stratifying technique, number and territory of
the endarterectomy and conduit type in order to determine the patients in whom
open-CE may confer the greatest benefit.
PMID- 25114126
TI - Identification of Acinetobacter baumannii serum-associated antibiotic efflux pump
inhibitors.
AB - Adaptive antibiotic resistance is a newly described phenomenon by which
Acinetobacter baumannii induces efflux pump activity in response to host
associated environmental cues that may, in part, account for antibiotic treatment
failures against clinically defined susceptible strains. To that end, during
adaptation to growth in human serum, the organism induces approximately 22
putative efflux-associated genes and displays efflux-mediated minocycline
tolerance at antibiotic concentrations corresponding to patient serum levels.
Here, we show that in addition to minocycline, growth in human serum elicits A.
baumannii efflux-mediated tolerance to the antibiotics ciprofloxacin, meropenem,
tetracycline, and tigecycline. Moreover, using a whole-cell high-throughput
screen and secondary assays, we identified novel serum-associated antibiotic
efflux inhibitors that potentiated the activities of antibiotics toward serum
grown A. baumannii. Two compounds, Acinetobacter baumannii efflux pump inhibitor
1 (ABEPI1) [(E)-4-((4-chlorobenzylidene)amino)benezenesulfonamide] and ABEPI2 [N
tert-butyl-2-(1-tert-butyltetrazol-5-yl)sulfanylacetamide], were shown to lead to
minocycline accumulation within A. baumannii during serum growth and inhibit the
efflux potential of the organism. While both compounds also inhibited the
antibiotic efflux properties of the bacterial pathogen Pseudomonas aeruginosa,
they did not display significant cytotoxicity toward human cells or mammalian
Ca(2+) channel inhibitory effects, suggesting that ABEPI1 and ABEPI2 represent
promising structural scaffolds for the development of new classes of bacterial
antibiotic efflux pump inhibitors that can be used to potentiate the activities
of current and future antibiotics for the therapeutic intervention of Gram
negative bacterial infections.
PMID- 25114127
TI - A first-in-human randomized, double-blind, placebo-controlled, single- and
multiple-ascending oral dose study of novel antimalarial Spiroindolone KAE609
(Cipargamin) to assess its safety, tolerability, and pharmacokinetics in healthy
adult volunteers.
AB - This first-in-human randomized, double-blind, placebo-controlled, ascending
single and -multiple oral dose study was designed to evaluate the safety,
tolerability, and pharmacokinetics in healthy volunteers of KAE609 (cipargamin;
formerly NITD609), a spiroindolone now in trials for malaria treatment. It was
studied in single-dose cohorts (1 to 300 mg, including one 30-mg food effect
cohort) with 4 to 10 subjects in each cohort and in multiple-dose cohorts (10 to
150 mg once daily for 3 days) with 8 subjects in each cohort. The follow-up
period was 6 to 8 days post-last dose. Safety and pharmacokinetics were assessed
at scheduled time points during the study. Systemic exposure in terms of the area
under the concentration-time curve from 0 h extrapolated to infinity (AUC0
infinity) increased in a dose-proportional manner over the dose range of 1 to 300
mg. The AUC from time zero to the time of the last quantifiable concentration
(AUClast) and the maximum concentration of drug in plasma (Cmax) also increased
in an approximately dose-proportional manner. When administered daily for 3 days,
the accumulation ratio on day 3 (the AUC from time zero to 24 h postdosing [AUC0
24] on day 3/AUC0-24 on day 1) was in the range of 1.5 to 2 in the studied dose
range (10 to 150 mg) and was consistent with an elimination half-life of around
24 h. Urine analysis for unchanged KAE609 revealed negligible amounts (<=0.01%)
were excreted renally. The high fat food intake did not affect the extent of
KAE609 absorption (AUC); however, the Cmax was reduced by around 27%. KAE609 was
tolerated in this study, with transient gastrointestinal and genitourinary
adverse events of mild to moderate intensity (semen discoloration, diarrhea,
nausea and abdominal discomfort, dizziness and headache, catheter site hematoma).
Gastrointestinal and genitourinary adverse events increased with rising doses.
PMID- 25114128
TI - Ascorbate peroxidase, a key molecule regulating amphotericin B resistance in
clinical isolates of Leishmania donovani.
AB - Amphotericin B (AmB), a polyene macrolide, is now a first-line treatment of
visceral leishmaniasis cases refractory to antimonials in India. AmB relapse
cases and the emergence of secondary resistance have now been reported. To
understand the mechanism of AmB, differentially expressed genes in AmB resistance
strains were identified by a DNA microarray and real-time reverse transcriptase
PCR (RT-PCR) approach. Of the many genes functionally overexpressed in the
presence of AmB, the ascorbate peroxidase gene from a resistant Leishmania
donovani strain (LdAPx gene) was selected because the gene is present only in
Leishmania, not in humans. Apoptosis-like cell death after exposure to AmB was
investigated in a wild-type (WT) strain in which the LdAPx gene was overexpressed
and in AmB-sensitive and -resistant strains. A higher percentage of apoptosis
like cell death after AmB treatment was noticed in the sensitive strain than in
both the resistant isolate and the strain sensitive to LdAPx overexpression. This
event is preceded by AmB-induced formation of reactive oxygen species and
elevation of the cytosolic calcium level. Enhanced cytosolic calcium was found to
be responsible for depolarization of the mitochondrial membrane potential and the
release of cytochrome c (Cyt c) into the cytosol. The redox behavior of Cyt c
showed that it has a role in the regulation of apoptosis-like cell death by
activating metacaspase- and caspase-like proteins and causing concomitant nuclear
alterations, as determined by terminal deoxynucleotidyltransferase-mediated dUTP
biotin nick end labeling (TUNEL) and DNA fragmentation in the resistant strain.
The present study suggests that constitutive overexpression of LdAPx in the L.
donovani AmB-resistant strain prevents cells from the deleterious effect of
oxidative stress, i.e., mitochondrial dysfunction and cellular death induced by
AmB.
PMID- 25114129
TI - Resveratrol is active against Leishmania amazonensis: in vitro effect of its
association with Amphotericin B.
AB - Resveratrol is a polyphenol found in black grapes and red wine and has many
biological activities. In this study, we evaluated the effect of resveratrol
alone and in association with amphotericin B (AMB) against Leishmania
amazonensis. Our results demonstrate that resveratrol possesses both
antipromastigote and antiamastigote effects, with 50% inhibitory concentrations
(IC50s) of 27 and 42 MUM, respectively. The association of resveratrol with AMB
showed synergy for L. amazonensis amastigotes, as demonstrated by the mean sums
of fractional inhibitory index concentration (mean SigmaFIC) of 0.483, although
for promastigotes, this association was indifferent. Treatment with resveratrol
increased the percentage of promastigotes in the sub-G0/G1 phase of the cell
cycle, reduced the mitochondrial potential, and showed an elevated choline peak
and CH2-to-CH3 ratio in the nuclear magnetic resonance (NMR) spectroscopy
analysis; all these features indicate parasite death. Resveratrol also decreased
the activity of the enzyme arginase in uninfected and infected macrophages with
and without stimulation with interleukin-4 (IL-4), also implicating arginase
inhibition in parasite death. The anti-Leishmania effect of resveratrol and its
potential synergistic association with AMB indicate that these compounds should
be subjected to further studies of drug association therapy in vivo.
PMID- 25114130
TI - Combination of the CCL5-derived peptide R4.0 with different HIV-1 blockers
reveals wide target compatibility and synergic cobinding to CCR5.
AB - R4.0, a synthetic CCL5/RANTES-derived peptide, exerts potent anti-HIV-1 activity
via its nonactivating interaction with CCR5, the major HIV-1 coreceptor. CCR5
chronic activation may promote undesirable inflammatory effects and enhance viral
infection; thus, receptor antagonism is a necessary requisite. HIV-1 gp120, CCL5,
and maraviroc dock on CCR5 by sharing two receptor sites: the N terminus and the
second extracellular loop. In combination studies, R4.0, CCL5, and maraviroc
exhibited concomitant interactions with CCR5 and promoted synergic inhibition of
HIV-1 in acute-infection assays. Furthermore, various degrees of
additive/synergic HIV-1 inhibition were observed when R4.0 was tested in
combination with drugs and lead compounds directed toward different viral targets
(gp120, gp41, reverse transcriptase, and protease). In combination with
tenofovir, R4.0 provides cross-clade synergic inhibition of primary HIV-1
isolates. Remarkably, an in vitro-generated maraviroc-resistant R5 HIV-1 strain
was inhibited by R4.0 comparably to the wild-type strain, suggesting the presence
of viral resistance barriers similar to those reported for CCL5. Overall, R4.0
appears to be a promising lead peptide with potential for combination in anti-HIV
1 therapy and in microbicide development to prevent sexual HIV-1 transmission.
PMID- 25114131
TI - Chloroquine has a cytotoxic effect on Acanthamoeba encystation through modulation
of autophagy.
AB - Encystation of Acanthamoeba castellanii is associated with resistance to
chemotherapeutic agents. Blocking the encystation process could potentiate the
efficacy of chemotherapeutic agents and biocides. During encystation, autophagy
is highly stimulated and required for proper encystation of Acanthamoeba. In this
study, the cytotoxic effect of chloroquine, a well-known autophagy-inhibitory
drug, was tested in A. castellanii. Chloroquine was able to selectively reduce
cell survival during the encystation of A. castellanii. However, A. castellanii
trophozoites and mature cysts were resistant to chloroquine. Chloroquine
treatment led to an increase in the number and size of lysosomes in encysting
cells. Moreover, chloroquine inhibited the degradation of long-lived proteins in
the encysting cells. Decreased autophagic flux, indicated by an increased number
of lysosomes and decreased degradation of long-lived proteins, may be the
mechanism by which cell death is induced by chloroquine in encysting
Acanthamoeba. These results suggest a potential novel therapeutic application of
chloroquine as an anti-Acanthamoeba drug. Our findings also suggest that
targeting autophagy could be a therapeutic strategy against Acanthamoeba
infection.
PMID- 25114132
TI - Pharmacokinetics of para-aminosalicylic acid in HIV-uninfected and HIV-coinfected
tuberculosis patients receiving antiretroviral therapy, managed for multidrug
resistant and extensively drug-resistant tuberculosis.
AB - The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR)
Mycobacterium tuberculosis prompted the reintroduction of para-aminosalicylic
acid (PAS) to protect companion anti-tuberculosis drugs from additional acquired
resistance. In sub-Saharan Africa, MDR/XDR tuberculosis with HIV coinfection is
common, and concurrent treatment of HIV infection and MDR/XDR tuberculosis is
required. Out of necessity, patients receive multiple drugs, and PAS therapy is
frequent; however, neither potential drug interactions nor the effects of HIV
infection are known. Potential drug-drug interaction with PAS and the effect of
HIV infection was examined in 73 pulmonary tuberculosis patients; 22 (30.1%) were
HIV coinfected. Forty-one pulmonary MDR or XDR tuberculosis patients received 4 g
PAS twice daily, and in a second crossover study, another 32 patients were
randomized, receiving 4 g PAS twice daily or 8 g PAS once daily. A PAS population
pharmacokinetic model in two dosing regimens was developed; potential covariates
affecting its pharmacokinetics were examined, and Monte Carlo simulations were
conducted evaluating the pharmacokinetic-pharmacodynamic index. The probability
of target attainment (PTA) to maintain PAS levels above MIC during the dosing
interval was estimated by simulation of once-, twice-, and thrice-daily dosing
regimens not exceeding 12 g daily. Concurrent efavirenz (EFV) medication resulted
in a 52% increase in PAS clearance and a corresponding >30% reduction in mean PAS
area under the concentration curve in 19 of 22 HIV-M. tuberculosis-coinfected
patients. Current practice recommends maintenance of PAS concentrations at >=1
MUg/ml (the MIC of M. tuberculosis), but the model predicts that at only a
minimum dose of 4 g twice daily can this PTA be achieved in at least 90% of the
population, whether or not EFV is concomitantly administered. Once-daily dosing
of 12 g PAS will not provide PAS concentrations exceeding the MIC over the entire
dosing interval if coadministered with EFV, while 4 g twice daily ensures
concentrations exceeding MIC over the entire dosing interval, even in HIV
infected patients who received EFV.
PMID- 25114133
TI - Molecular mechanism of MBX2319 inhibition of Escherichia coli AcrB multidrug
efflux pump and comparison with other inhibitors.
AB - Efflux pumps of the resistance nodulation division (RND) superfamily, such as
AcrB, make a major contribution to multidrug resistance in Gram-negative
bacteria. The development of inhibitors of the RND pumps would improve the
efficacy of current and next-generation antibiotics. To date, however, only one
inhibitor has been cocrystallized with AcrB. Thus, in silico structure-based
analysis is essential for elucidating the interaction between other inhibitors
and the efflux pumps. In this work, we used computer docking and molecular
dynamics simulations to study the interaction between AcrB and the compound
MBX2319, a novel pyranopyridine efflux pump inhibitor with potent activity
against RND efflux pumps of Enterobacteriaceae species, as well as other known
inhibitors (D13-9001, 1-[1-naphthylmethyl]-piperazine, and phenylalanylarginine
beta-naphthylamide) and the binding of doxorubicin to the efflux-defective F610A
variant of AcrB. We also analyzed the binding of a substrate, minocycline, for
comparison. Our results show that MBX2319 binds very tightly to the lower part of
the distal pocket in the B protomer of AcrB, strongly interacting with the
phenylalanines lining the hydrophobic trap, where the hydrophobic portion of D13
9001 was found to bind by X-ray crystallography. Additionally, MBX2319 binds to
AcrB in a manner that is similar to the way in which doxorubicin binds to the
F610A variant of AcrB. In contrast, 1-(1-naphthylmethyl)-piperazine and
phenylalanylarginine-beta-naphthylamide appear to bind to somewhat different
areas of the distal pocket in the B protomer of AcrB than does MBX2319. However,
all inhibitors (except D13-9001) appear to distort the structure of the distal
pocket, impairing the proper binding of substrates.
PMID- 25114134
TI - UDP-N-acetylmuramic acid l-alanine ligase (MurC) inhibition in a tolC mutant
Escherichia coli strain leads to cell death.
AB - The Mur ligases play an essential role in the biosynthesis of bacterial
peptidoglycan and hence are attractive antibacterial targets. A screen of the
AstraZeneca compound library led to the identification of compound A, a
pyrazolopyrimidine, as a potent inhibitor of Escherichia coli and Pseudomonas
aeruginosa MurC. However, cellular activity against E. coli or P. aeruginosa was
not observed. Compound A was active against efflux pump mutants of both strains.
Experiments using an E. coli tolC mutant revealed accumulation of the MurC
substrate and a decrease in the level of product upon treatment with compound A
,: indicating inhibition of MurC enzyme in these cells. Such a modulation was not
observed in the E. coli wild-type cells. Further, overexpression of MurC in the
E. coli tolC mutant led to an increase in the compound A MIC by >=16-fold,
establishing a correlation between MurC inhibition and cellular activity. In
addition, estimation of the intracellular compound A level showed an accumulation
of the compound over time in the tolC mutant strain. A significant compound A
level was not detected in the wild-type E. coli strain even upon treatment with
high concentrations of the compound. Therefore, the lack of MIC and absence of
MurC inhibition in wild-type E. coli were possibly due to suboptimal compound
concentration as a consequence of a high efflux level and/or poor permeativity of
compound A.
PMID- 25114135
TI - A clinical adverse drug reaction prediction model for patients with chagas
disease treated with benznidazole.
AB - Benznidazole (BZN) is the main trypanocidal drug used to treat Chagas disease,
and the evidence supporting the benefits of BZN use during the chronic phase of
the disease will favor its use in millions of individuals. However, more than 30%
of patients treated with BZN may suffer adverse drug reactions (ADRs), and the
development of tools to identify those patients at risk is highly desirable. In
the present study, we aimed to identify predictive factors for ADRs in Chagas
disease patients treated with BZN. Among 195 patients included in the study,
48.7% experienced ADRs and 31.3% had ADRs that caused BZN treatment
discontinuation. Overall ADRs and ADRs that caused BZN treatment discontinuation
were more common among women and in those who graduated from elementary school.
Overall ADRs were also less frequent among black individuals. Based on logistic
regression analysis, female sex (odds ratio [OR], 2.9; 95% confidence interval
[CI], 1.5 to 5.4), graduation from elementary school (OR, 2.0; 95% CI, 1.1 to
3.8), and white (OR, 5.0; 95% CI, 1.0 to 24.1) and mulatto (OR, 5.6; 95% CI, 1.1
to 28.7) races were considered to predict overall ADRs, and female sex (OR, 2.3;
95% CI, 1.2 to 4.3) was considered to predict ADRs that caused BZN treatment
discontinuation. Graduation from elementary school also presented a tendency to
predict ADRs that caused BZN treatment discontinuation (OR, 1.8; 95% CI, 0.9 to
3.6). The logistic regression (LR) models to predict ADRs to BZN described in
this study may become important tools to minimize ADRs and improve patients'
compliance and thus assist physicians treating patients with Chagas disease with
BZN.
PMID- 25114136
TI - Emergence of KPC-2-Producing Salmonella enterica Serotype Schwarzengrund in
Argentina.
PMID- 25114137
TI - Overproduction of Ristomycin A by activation of a silent gene cluster in
Amycolatopsis japonicum MG417-CF17.
AB - The emergence of antibiotic-resistant pathogenic bacteria within the last decades
is one reason for the urgent need for new antibacterial agents. A strategy to
discover new anti-infective compounds is the evaluation of the genetic capacity
of secondary metabolite producers and the activation of cryptic gene clusters
(genome mining). One genus known for its potential to synthesize medically
important products is Amycolatopsis. However, Amycolatopsis japonicum does not
produce an antibiotic under standard laboratory conditions. In contrast to most
Amycolatopsis strains, A. japonicum is genetically tractable with different
methods. In order to activate a possible silent glycopeptide cluster, we
introduced a gene encoding the transcriptional activator of balhimycin
biosynthesis, the bbr gene from Amycolatopsis balhimycina (bbrAba), into A.
japonicum. This resulted in the production of an antibiotically active compound.
Following whole-genome sequencing of A. japonicum, 29 cryptic gene clusters were
identified by genome mining. One of these gene clusters is a putative
glycopeptide biosynthesis gene cluster. Using bioinformatic tools, ristomycin
(syn. ristocetin), a type III glycopeptide, which has antibacterial activity and
which is used for the diagnosis of von Willebrand disease and Bernard-Soulier
syndrome, was deduced as a possible product of the gene cluster. Chemical
analyses by high-performance liquid chromatography and mass spectrometry (HPLC
MS), tandem mass spectrometry (MS/MS), and nuclear magnetic resonance (NMR)
spectroscopy confirmed the in silico prediction that the recombinant A.
japonicum/pRM4-bbrAba synthesizes ristomycin A.
PMID- 25114139
TI - resistome analysis of Enterobacter cloacae CY01, an extensively drug-resistant
strain producing VIM-1 metallo-beta-lactamase from China.
AB - Resistome analysis of clinical VIM-1-producing Enterobacter cloacae strain CY01
from China revealed the presence of multiple resistance determinants. Two
resistance plasmids were identified in CY01. The pCY-VIM plasmid was 14 kb in
size and possessed a replicase gene (repA), a gene cluster encoding the
partitioning function (parABC), and a carbapenemase gene (blaVIM-1). Another 5.9
kb plasmid, pCY-MdT, with an aac(6')-Ib gene, was very closely related (13
nucleotide differences) to pMdT1, a ColE1 plasmid carrying aac(6')-Ib-cr4.
PMID- 25114138
TI - Antimalarial activity of the myxobacterial macrolide chlorotonil a.
AB - Myxobacteria are Gram-negative soil-dwelling bacteria belonging to the phylum
Proteobacteria. They are a rich source of promising compounds for clinical
application, such as epothilones for cancer therapy and several new antibiotics.
In the course of a bioactivity screening program of secondary metabolites
produced by Sorangium cellulosum strains, the macrolide chlorotonil A was found
to exhibit promising antimalarial activity. Subsequently, we evaluated
chlorotonil A against Plasmodium falciparum laboratory strains and clinical
isolates from Gabon. Chlorotonil A was highly active, with a 50% inhibitory
concentration between 4 and 32 nM; additionally, no correlations between the
activities of chlorotonil A and artesunate (rho, 0.208) or chloroquine (rho,
0.046) were observed. Per os treatment of Plasmodium berghei-infected mice with
four doses of as little as 36 mg of chlorotonil A per kg of body weight led to
the suppression of parasitemia with no obvious signs of toxicity. Chlorotonil A
acts against all stages of intraerythrocytic parasite development, including ring
stage parasites and stage IV to V gametocytes, and it requires only a very short
exposure to the parasite to exert its antimalarial action. Conclusively,
chlorotonil A has an exceptional and unprecedented profile of action and
represents an urgently required novel antimalarial chemical scaffold. Therefore,
we propose it as a lead structure for further development as an antimalarial
chemotherapeutic.
PMID- 25114140
TI - Impact of lopinavir-ritonavir or nevirapine on bedaquiline exposures and
potential implications for patients with tuberculosis-HIV coinfection.
AB - Concomitant treatment of tuberculosis (TB) and HIV is recommended and improves
outcomes. Bedaquiline is a novel drug for the treatment of multidrug-resistant
(MDR) TB; combined use with antiretroviral drugs, nevirapine, or ritonavir
boosted lopinavir (LPV/r) is anticipated, but no clinical data from coinfected
patients are available. Plasma concentrations of bedaquiline and its M2
metabolite after single doses were obtained from interaction studies with
nevirapine or LPV/r in healthy volunteers. The antiretrovirals' effects on
bedaquiline and M2 pharmacokinetics were assessed by nonlinear mixed-effects
modeling. Potential dose adjustments were evaluated with simulations. No
significant effects of nevirapine on bedaquiline pharmacokinetics were
identified. LPV/r decreased bedaquiline and M2 clearances to 35% (relative
standard error [RSE], 9.2%) and 58% (RSE, 8.4%), respectively, of those without
comedication. As almost 3-fold (bedaquiline) and 2-fold (M2) increases in
exposures during chronic treatment with LPV/r are expected, dose adjustments are
suggested for evaluation. Efficacious, safe bedaquiline dosing for MDR-TB
patients receiving antiretrovirals is important. Modeling results suggest that
bedaquiline can be coadministered with nevirapine without dose adjustments. The
predicted elevation of bedaquiline and M2 levels during LPV/r coadministration
may be a safety concern, and careful monitoring is recommended. Further data are
being collected in coinfected patients to determine whether dose adjustments are
needed. (These studies have been registered at ClinicalTrials.gov under
registration numbers NCT00828529 [study C110] and NCT00910806 [study C117].).
PMID- 25114141
TI - In vitro susceptibility of Plasmodium vivax to antimalarials in Colombia.
AB - The in vitro susceptibilities of 30 isolates of Plasmodium vivax to a number of
antimalarials (chloroquine [CQ], mefloquine, amodiaquine, quinine, and artesunate
[AS]) were evaluated. The isolates came from the region of Uraba in Colombia, in
which malaria is endemic, and were evaluated by the schizont maturation test. The
50% inhibitory concentration (IC50) was 0.6 nM (95% confidence interval [CI], 0.3
to 1.0 nM) for artesunate, 8.5 nM (95% CI, 5.6 to 13.0 nM) for amodiaquine, 23.3
nM (95% CI, 12.4 to 44.1 nM) for chloroquine, 55.6 nM (95% CI, 36.8 to 84.1 nM)
for mefloquine, and 115.3 nM (95% CI, 57.7 to 230.5 nM) for quinine. The isolates
were classified according to whether the initial parasites were mature or
immature trophozoites (Tfz). It was found that the IC50s for chloroquine and
artesunate were significantly different in the two aforementioned groups (P <
0.001). The IC50s of CQ and AS were higher in the isolates from mature Tfz (CQ,
39.3 nM versus 17 nM; AS, 1.4 nM versus 0.3 nM), and 10% of the isolates showed
lower susceptibilities to one of the antimalarial drugs, 13.3% to two
antimalarial drugs, and 3.3% to more than three antimalarial drugs. It should be
highlighted that despite the extensive use of chloroquine in Colombia, P. vivax
continues to be susceptible to antimalarials. This is the first report, to our
knowledge, showing in vitro susceptibilities of P. vivax isolates to
antimalarials in Colombia.
PMID- 25114144
TI - Death of an alienist: Louis-Victor Marce's final year.
AB - The cause of death, at the age of 37, of Louis-Victor Marce (1828-64), one of the
most innovative alienists of the nineteenth century, was concealed by his
contemporaries and colleagues. Recently it has been discovered that he committed
suicide, but the circumstances and reasons for this were unknown. Information has
now been found about his family, the events of the last year of his life and an
unprecedented correspondence from his father-in-law, the chemist and academician
Jules Pelouze, describing Marce's condition during the last month of his life.
All of these point towards a diagnosis of melancholy, for which none of the
appropriate measures were taken, probably as a result of the ailing Marce's
social situation.
PMID- 25114142
TI - Comparison of the antibiotic activities of Daptomycin, Vancomycin, and the
investigational Fluoroquinolone Delafloxacin against biofilms from Staphylococcus
aureus clinical isolates.
AB - Biofilm-related infections remain a scourge. In an in vitro model of biofilms
using Staphylococcus aureus reference strains, delafloxacin and daptomycin were
found to be the most active among the antibiotics from 8 different
pharmacological classes (J. Bauer, W. Siala, P. M. Tulkens, and F. Van Bambeke,
Antimicrob. Agents Chemother. 57:2726-2737, 2013, doi:10.1128/AAC.00181-13). In
this study, we compared delafloxacin to daptomycin and vancomycin using biofilms
produced by 7 clinical strains (S. aureus epidemic clones CC5 and CC8) in order
to rationalize the differences observed between the antibiotics and strains. The
effects of the antibiotics on bacterial viability (resazurin reduction assay) and
biomass (crystal violet staining) were measured and correlated with the
proportion of polysaccharides in the matrix, the local microenvironmental pH
(micro-pH), and the antibiotic penetration in the biofilm. At clinically
meaningful concentrations, delafloxacin, daptomycin, and vancomycin caused a
>=25% reduction in viability against the biofilms formed by 5, 4, and 3 strains,
respectively. The antibiotic penetration within the biofilms ranged from 0.6 to
52% for delafloxacin, 0.2 to 10% for daptomycin, and 0.2 to 1% for vancomycin;
for delafloxacin, this was inversely related to the polysaccharide proportion in
the matrix. Six biofilms were acidic, explaining the high potency of delafloxacin
(lower MICs at acidic pH). Norspermidine and norspermine (disassembling the
biofilm matrix) drastically increased delafloxacin potency and efficacy (50%
reduction in viability for 6 biofilms at clinically meaningful concentrations) in
direct correlation with its increased penetration within the biofilm, while they
only modestly improved daptomycin efficacy (50% reduction in viability for 2
biofilms) and penetration, and they showed marginal effects with vancomycin.
Delafloxacin potency and efficacy against biofilms are benefited by its
penetration into the matrix and the local acidic micro-pH.
PMID- 25114145
TI - 'The world is full of big bad wolves': investigating the experimental therapeutic
spaces of R.D. Laing and Aaron Esterson.
AB - In conjunction with the recent critical assessments of the life and work of R.D.
Laing, this paper seeks to demonstrate what is revealed when Laing's work on
families and created spaces of mental health care are examined through a
geographical lens. The paper begins with an exploration of Laing's time at the
Tavistock Clinic in London during the 1960s, and of the co-authored text with
Aaron Esterson entitled, Sanity, Madness and the Family (1964). The study then
seeks to demonstrate the importance Laing and his colleague placed on the time
space situatedness of patients and their worlds. Finally, an account is provided
of Laing's and Esterson's spatial thinking in relation to their creation of both
real and imagined spaces of therapeutic care.
PMID- 25114143
TI - Evolution of oseltamivir resistance mutations in Influenza A(H1N1) and A(H3N2)
viruses during selection in experimentally infected mice.
AB - The evolution of oseltamivir resistance mutations during selection through serial
passages in animals is still poorly described. Herein, we assessed the evolution
of neuraminidase (NA) and hemagglutinin (HA) genes of influenza A/WSN/33 (H1N1)
and A/Victoria/3/75 (H3N2) viruses recovered from the lungs of experimentally
infected BALB/c mice receiving suboptimal doses (0.05 and 1 mg/kg of body
weight/day) of oseltamivir over two generations. The traditional phenotypic and
genotypic methods as well as deep-sequencing analysis were used to characterize
the potential selection of mutations and population dynamics of oseltamivir
resistant variants. No oseltamivir-resistant NA or HA changes were detected in
the recovered A/WSN/33 viruses. However, we observed a positive selection of the
I222T NA substitution in the recovered A/Victoria/3/75 viruses, with a frequency
increasing over time and with an oseltamivir concentration from 4% in the initial
pretherapy inoculum up to 28% after two lung passages. Although the presence of
mixed I222T viral populations in mouse lungs only led to a minimal increase in
oseltamivir 50% enzyme-inhibitory concentrations (IC50s) (by a mean of 5.7-fold)
compared to that of the baseline virus, the expressed recombinant A/Victoria/3/75
I222T NA protein displayed a 16-fold increase in the oseltamivir IC50 level
compared to that of the recombinant wild type (WT). In conclusion, the
combination of serial in vivo passages under neuraminidase inhibitor (NAI)
pressure and temporal deep-sequencing analysis enabled, for the first time, the
identification and selection of the oseltamivir-resistant I222T NA mutation in an
influenza H3N2 virus. Additional in vivo selection experiments with other
antivirals and drug combinations might provide important information on the
evolution of antiviral resistance in influenza viruses.
PMID- 25114147
TI - Karl Jaspers on the disease entity: Kantian ideas and Weberian ideal types.
AB - Jaspers' nosology is indebted to Immanuel Kant's theory of knowledge. He drew the
distinction of form and content from the Transcendental Analytic of Kant's
Critique of Pure Reason. The distinction is universal to all knowledge, including
psychopathology. Individual experience is constituted by a form or category of
the Understanding to give a determinate or knowable object classified into the
generic type of a real disease entity. The application of form and content is
limited by the boundaries of experience. Beyond this boundary are wholes whose
conception requires Ideas of reason drawn from the Transcendental Dialectic.
Wholes are regulated by Ideas of reason to give an object or schema of the Idea
collected into ideal types of an ideal typical disease entity. Jaspers drew ideal
types from Max Weber's social theory. He anticipated that, as knowledge advanced,
ideal typical disease entities would become real disease entities. By 1920, this
had been the destiny of general paralysis as knowledge of its neuropathology,
serology and microbiology emerged. As he presented the final edition of General
Psychopathology in 1946, Jaspers was anticipating the transition of schizophrenia
from ideal typical to real disease entity. Almost 70 years later, with knowledge
of its aetiology still unclear, schizophrenia remains marooned as an ideal
typical disease entity - still awaiting that crucial advance!
PMID- 25114146
TI - From paranoia querulans to vexatious litigants: a short study on madness between
psychiatry and the law. Part 1.
AB - The first part of this two-part paper presents a comparative history of paranoia
querulans, also known as litigants' delusion, in German-speaking countries and
France from the nineteenth century onwards. We first focus on two classic
literary works which describe litigious behaviours that were later pathologized,
then give an insight into the history of Querulantenwahn (litigants' delusion), a
term coined in 1857 by Johann Ludwig Casper and adopted by German-speaking
psychiatrists and forensic experts. The last section is devoted to its French
equivalent, the delusion of the litigious persecuted-persecutors. We show how
this category, widely popular among French fin-de-siecle alienists, was replaced
by another: the delusion of revendication (litigious subtype). The history of the
vexatious litigants in the English-speaking world will be explored in the Part 2.
PMID- 25114149
TI - From the Netherlands to Japan: communicating psychiatric practice in the 1830s.
AB - This article explores an example of the transmission of Dutch psychiatric
knowledge to Japan in the Edo period (1600-1868), through the translation of a
case study first published by Schroeder van der Kolk in 1826. The translation
appeared in an innovative new journal of Western medicine edited by the Japanese
rangaku (Dutch-learning) scholar, Mitsukuri Genpo. The case study describes the
symptoms and treatment of a woman who experienced delusions following an ear
infection, in terms largely familiar to the Japanese doctors of the time. This
translation provides opportunities to consider the globalization and localization
of psychiatric knowledge, the medicalization of mental health care in Japan, and
the growing interest in Western psychiatry before its official introduction to
Japan after 1868.
PMID- 25114148
TI - Demonic possession and the historical construction of melancholy and hysteria.
AB - Contrary to the often-voiced opinion that the birth of modern psychiatry should
be regarded as a victory of enlightened science and rationality over outdated
religious beliefs and ecclesiastical authority, it is argued in this article that
the emergence of medical and psychiatric approaches to pathology in modernity
takes place in the context of intensified religious life and mutual rivalry
between the various religious denominations. Notably the two main types of
demonological possession appearing in the context of Protestant and Catholic
religious life, theological reflections and pastoral practices play a major role
in the conceptualizations of melancholy and hysteria. The heritage of this can be
viewed in the works of psychiatrists such as Charcot and Kraepelin, and also in
Freud's psychoanalysis.
PMID- 25114150
TI - J.H. Pons on 'Sympathetic insanity': With an introduction by GE Berrios.
AB - The ancient concept of 'sympathy' originally referred to a putative affinity or
force that linked all natural objects together. This notion was later used to
explain the manner in which human beings related and felt for each other. A large
literature exists on both the physical and psychological definitions of sympathy.
Until the nineteenth century the conceptual apparatus of medicine preserved the
view that the organs of the human body had a sympathetic affinity for each other.
In addition to these 'physiological' (normal) sympathies there were morbid ones
which explained the existence of various diseases. A morbid sympathy link also
explained the fact that insanity followed the development of pathological changes
in the liver, spleen, stomach and other bodily organs. These cases were
classified as 'sympathetic insanities'. After the 1880s, the sympathy narrative
was gradually replaced by physiological, endocrinological and psychodynamic
explanations. The clinical states involved, however, are often observed in
hospital practice and constitute the metier of 'consultation-liaison psychiatry'.
Hence, it is surprising that historical work on the development of this
discipline has persistently ignored the concept of 'sympathetic insanity'.
PMID- 25114157
TI - Minicystis rosea gen. nov., sp. nov., a polyunsaturated fatty acid-rich and
steroid-producing soil myxobacterium.
AB - A bacterial strain designated SBNa008(T) was isolated from a Philippine soil
sample. It exhibited the general characteristics associated with myxobacteria,
such as swarming of Gram-negative vegetative rod cells, fruiting body and
myxospore formation and predatory behaviour in lysing micro-organisms. The novel
strain was characterized as mesophilic, chemoheterotrophic and aerobic. The major
fatty acids were C(20:4)omega6,9,12,15 all cis (arachidonic acid), iso-C(15 : 0),
C(17 : 1) 2-OH and iso-C(15 : 0) dimethylacetal. Interestingly, SBNa008(T)
contained diverse fatty acids belonging to the commercially valuable
polyunsaturated omega-6 and omega-3 families, and a highly conjugated
dihydroxylated C28 steroid. The G+C content of the genomic DNA was 67.3 mol%. The
16S rRNA gene sequence revealed 95-96% similarity to sequences derived from
clones of uncultured bacteria and 94-95% similarity to cultured members of the
suborder Sorangiineae. Phylogenetic analysis revealed that strain SBNa008(T)
formed a novel lineage in the suborder Sorangiineae. Based on a polyphasic
taxonomic characterization, we propose that strain SBNa008(T) represents a novel
genus and species, Minicystis rosea gen. nov., sp. nov. The type strain of
Minicystis rosea is SBNa008(T) ( =DSM 24000(T) =NCCB 100349(T)).
PMID- 25114159
TI - Demographic evidence of sex differences in vulnerability to infectious diseases.
PMID- 25114158
TI - Mesoflavibacter sabulilitoris sp. nov., isolated from seashore sand.
AB - A Gram-stain-negative, aerobic, non-spore-forming, non-flagellated, gliding and
rod-shaped bacterial strain, designated GJMS-9(T), was isolated from seashore
sand collected at Geoje island in the South Sea, South Korea. Strain GJMS-9(T)
grew optimally at 30 degrees C, at pH 7.0-8.0 and in the presence of 2.0% (w/v)
NaCl. Phylogenetic trees based on 16S rRNA gene sequences revealed that strain
GJMS-9(T) clustered with the type strain of Mesoflavibacter zeaxanthinifaciens,
showing the highest sequence similarity of 99.1%. Strain GJMS-9(T) exhibited 16S
rRNA gene sequence similarity of 96.5% to the type strain of Mesoflavibacter
aestuarii and of less than 96.1% to the type strains of other recognized species.
Strain GJMS-9(T) contained MK-6 as the only menaquinone and iso-C(15:1) G, iso
C(16:0) 3-OH, iso-C(15:0) and iso-C(17:0) 3-OH as the major fatty acids. The
polar lipid profile of strain GJMS-9(T) containing phosphatidylethanolamine, one
unidentified lipid and one unidentified glycolipid as major components was
similar to that of the type strain of M. zeaxanthinifaciens. The DNA G+C content
of strain GJMS-9(T) was 32.2 mol% and its DNA-DNA relatedness with M.
zeaxanthinifaciens DSM 18436(T) was 38 +/- 6.1%. The differential phenotypic
properties, together with the phylogenetic and genetic distinctiveness, revealed
that strain GJMS-9(T) is separated from other species of the genus
Mesoflavibacter. On the basis of the data presented, strain GJMS-9(T) is
considered to represent a novel species of the genus Mesoflavibacter, for which
the name Mesoflavibacter sabulilitoris sp. nov. is proposed. The type strain is
GJMS-9(T) ( =KCTC 42117(T) =CECT 8597(T)).
PMID- 25114160
TI - A multi-host approach for the systematic analysis of virulence factors in
Cryptococcus neoformans.
AB - A multi-host approach was followed to screen a library of 1201 signature-tagged
deletion strains of Cryptococcus neoformans mutants to identify previously
unknown virulence factors. The primary screen was performed using a
Caenorhabditis elegans-C. neoformans infection assay. The hits among these
strains were reconfirmed as less virulent than the wild type in the insect
Galleria mellonella-C. neoformans infection assay. After this 2-stage screen, and
to prioritize hits, we performed serial evaluations of the selected strains,
using the C. elegans model. All hit strains identified through these studies were
validated in a murine model of systemic cryptococcosis. Twelve strains were
identified through a stepwise screening assay. Among them, 4 (CSN1201, SRE1,
RDI1, and YLR243W) were previously discovered, providing proof of principle for
this approach, while the role of the remaining 8 genes (CKS101, CNC5600, YOL003C,
CND1850, MLH3, HAP502, MSL5, and CNA2580) were not previously described in
cryptococcal virulence. The multi-host approach is an efficient method of
studying the pathogenesis of C. neoformans. We used diverse model hosts, C.
elegans, G. mellonella, and mice, with physiological differences and identified
12 genes associated with mammalian infection. Our approach may be suitable for
large pathogenesis screens.
PMID- 25114161
TI - Appropriateness of clopidogrel use according to current recommendations.
AB - BACKGROUND: Clopidogrel is widely used in cardiovascular prevention. However, the
prescription of clopidogrel in clinical practice does not match the
recommendations concerning its indication and treatment duration. OBJECTIVE: To
assess the appropriateness of clopidogrel prescription according to the accepted
indications. METHODS: We undertook a retrospective observational analytical audit
of the electronic clinical records in the region of Valencia, Spain (5 million
inhabitants), selecting those patients on treatment with clopidogrel between 2007
and 2010. The primary outcome measure was the duration of the treatment. RESULTS:
A total of 45721 patients started clopidogrel treatment during the study period.
Treatment was for cardiologic disorders (CD) in 56.85% of the patients,
neurologic disorders (ND) in 37.06% and peripheral arterial disease in 6.08%.
Treatment duration was longer than that expected from clinical recommendations in
38.8% of the CD patients and 87.8% of the ND patients. The estimated avoidable
cost ranged from 2 to 4.4 million Euros per year, according to whether a cheaper
generic clopidogrel or a more expensive version was considered. CONCLUSIONS:
Almost 40% of the cardiologic patients and 90% of the neurologic patients
received excess treatment. Adjustment of treatment duration to international
recommendations would result in savings of between 80.1 and 176.3 Euros per year
and per patient treated.
PMID- 25114163
TI - Initiation of rilpivirine, tenofovir and emtricitabine (RPV/TDF/FTC) regimen in
363 patients with virological vigilance assessment in 'real life'.
AB - OBJECTIVES: To study the single-tablet regimen (STR) combination
rilpivirine/tenofovir/emtricitabine (RPV/TDF/FTC) as soon as it became available.
We describe a 14 month follow-up in a real clinical setting with a focus on
resistance to RPV/TDF/FTC and polymorphisms associated with these drugs. METHODS:
We estimated drug resistance at STR baseline by combining all available
resistance tests, resulting in a cumulative virtual genotype. Physicians were
advised of current or archived resistance mutations for the three drugs.
Virological response was analysed according to resistance genotype at baseline.
RESULTS: Three hundred and sixty-three patients received RPV/TDF/FTC; 79% had
received previous treatment and RPV/TDF/FTC was the result of a switch of one
drug to rilpivirine in two-thirds of cases. The cumulative genotype showed 4% of
rilpivirine resistance mutations at baseline and 16% of polymorphisms concerning
non-nucleoside reverse transcriptase inhibitors (NNRTIs). With a median duration
of STR of 8 months, 78% of patients with these polymorphisms were virologically
suppressed compared with 96% with wild-type genotypes. Five genotypes were
determined during the follow-up, revealing three rilpivirine resistance
associated mutations: E138Q/Y181I, M230L and K101P (potentially with a K101Q
intermediate). CONCLUSIONS: This observational study reflects routine clinical
practice and the relevance of virological advice. It also confirms the efficacy
of this STR (RPV/TDF/FTC) for naive and virologically suppressed pretreated
patients with a low prevalence of virological failure and resistance if the
cumulative baseline genotype is free of resistance to NNRTIs and/or polymorphisms
associated with NNRTIs.
PMID- 25114162
TI - HMBPP-deficient Listeria mutant immunization alters pulmonary/systemic responses,
effector functions, and memory polarization of Vgamma2Vdelta2 T cells.
AB - Whereas infection or immunization of humans/primates with microbes coproducing
HMBPP/IPP can remarkably activate Vgamma2Vdelta2 T cells, in vivo studies have
not been done to dissect HMBPP- and IPP-driven expansion, pulmonary trafficking,
effector functions, and memory polarization of Vgamma2Vdelta2 T cells. We define
these phosphoantigen-host interplays by comparative immunizations of macaques
with the HMBPP/IPP-coproducing Listeria DeltaactA prfA* and HMBPP-deficient
Listeria DeltaactA DeltaGCPE: prfA* mutant. The HMBPP-deficient DeltaGCPE: mutant
shows lower ability to expand Vgamma2Vdelta2 T cells in vitro than the parental
HMBPP-producing strain but displays comparably attenuated infectivity or
immunogenicity. Respiratory immunization of macaques with the HMBPP-deficient
mutant elicits lower pulmonary and systemic responses of Vgamma2Vdelta2 T cells
compared with the HMBPP-producing vaccine strain. Interestingly, HMBPP-deficient
mutant reimmunization or boosting elicits enhanced responses of Vgamma2Vdelta2 T
cells, but the magnitude is lower than that by HMBPP-producing listeria. HMBPP
deficient listeria differentiated fewer Vgamma2Vdelta2 T effector cells capable
of coproducing IFN-gamma and TNF-alpha and inhibiting intracellular listeria than
HMBPP-producing listeria. Furthermore, HMBPP deficiency in listerial immunization
influences memory polarization of Vgamma2Vdelta2 T cells. Thus, both HMBPP and
IPP production in listerial immunization or infection elicit systemic/pulmonary
responses and differentiation of Vgamma2Vdelta2 T cells, but a role for HMBPP is
more dominant. Findings may help devise immune intervention.
PMID- 25114164
TI - Antibiotic prophylaxis for transrectal prostate biopsy-a new strategy.
AB - BACKGROUND: Fluoroquinolones are extensively used as prophylaxis for transrectal
ultrasound-guided biopsy of the prostate (TRUBP). Emerging fluoroquinolone
resistance and selection of multiresistant organisms warrant new prophylactic
strategies. Pivmecillinam and amoxicillin/clavulanic acid have mutual synergistic
activity and the combination of these agents has a broad coverage of the majority
of microorganisms causing infectious complications after TRUBP and may be a
valuable future prophylactic regimen. PATIENTS AND METHODS: This was a
retrospective cohort study of 2624 men that underwent TRUBP at a Danish
university hospital. The patients were divided into three groups. Group 1 (n =
1220) received ciprofloxacin before TRUBP, Group 2 (n = 240) received a
combination of pivmecillinam and amoxicillin/clavulanic acid before TRUBP and
Group 3 (n = 1161) received an extended prophylaxis with pivmecillinam and
amoxicillin/clavulanic acid before and for 2 days after TRUBP. RESULTS: One
hundred and ten out of 148 (74.3%) post-TRUBP infections were caused by
Escherichia coli, Klebsiella pneumoniae or Enterococcus faecalis. Group 3 with
the extended prophylaxis with pivmecillinam and amoxicillin/clavulanic acid had a
significantly lower rate of bacteraemia (0.9%) as compared with Group 1 (1.8%)
and Group 2 (3.7%). A significant fall in the proportion of ESBL-producing
Enterobacteriaceae was observed from the period when ciprofloxacin was used as
prophylaxis (8.1%) compared with the subsequent period when pivmecillinam and
amoxicillin/clavulanic acid was used (5.9%). CONCLUSIONS: The combination of
pivmecillinam and amoxicillin/clavulanic acid is an attractive prophylaxis for
TRUBP from a clinical, bacteriological and ecological point of view as compared
with ciprofloxacin.
PMID- 25114165
TI - Kinetics of recA and recX induction in drug-susceptible and MDR clinical strains
of Mycobacterium tuberculosis.
AB - OBJECTIVES: To investigate and compare the expression of recA and recX,
components of the SOS pathway, following rifampicin treatment in drug-susceptible
and MDR clinical strains of Mycobacterium tuberculosis. METHODS: Strains (M.
tuberculosis and Mycobacterium smegmatis) were subjected to rifampicin- and
mitomycin-induced stress for 36 h followed by RNA extraction. recA and recX in
the RNA extract were estimated using qRT-PCR. RESULTS: The MDR clinical strain
induced faster (24 h) and higher (7-fold) levels of recA as compared with the
drug-susceptible strain (36 h) in response to rifampicin. recX levels were found
to rise with an increase in levels of recA; however, the levels were relatively
higher than recA. CONCLUSIONS: Drug-susceptible and MDR strains have different
kinetics of induction of DNA repair.
PMID- 25114166
TI - Proteus genomic island 1 (PGI1), a new resistance genomic island from two Proteus
mirabilis French clinical isolates.
AB - OBJECTIVES: To analyse the genetic environment of the antibiotic resistance genes
in two clinical Proteus mirabilis isolates resistant to multiple antibiotics.
METHODS: PCR, gene walking and whole-genome sequencing were used to determine the
sequence of the resistance regions, the surrounding genetic structure and the
flanking chromosomal regions. RESULTS: A genomic island of 81.1 kb named Proteus
genomic island 1 (PGI1) located at the 3'-end of trmE (formerly known as thdF)
was characterized. The large MDR region of PGI1 (55.4 kb) included a class 1
integron (aadB and aadA2) and regions deriving from several transposons: Tn2
(blaTEM-135), Tn21, Tn6020-like transposon (aphA1b), a hybrid Tn502/Tn5053
transposon, Tn501, a hybrid Tn1696/Tn1721 transposon [tetA(A)] carrying a class 1
integron (aadA1) and Tn5393 (strA and strB). Several ISs were also present
(IS4321, IS1R and IS26). The PGI1 backbone (25.7 kb) was identical to that
identified in Salmonella Heidelberg SL476 and shared some identity with the
Salmonella genomic island 1 (SGI1) backbone. An IS26-mediated recombination event
caused the division of the MDR region into two parts separated by a large
chromosomal DNA fragment of 197 kb, the right end of PGI1 and this chromosomal
sequence being in inverse orientation. CONCLUSIONS: PGI1 is a new resistance
genomic island from P. mirabilis belonging to the same island family as SGI1. The
role of PGI1 in the spread of antimicrobial resistance genes among
Enterobacteriaceae of medical importance needs to be evaluated.
PMID- 25114167
TI - Pharmacokinetics of oral isavuconazole in a patient after Roux-en-Y gastric
bypass surgery.
PMID- 25114168
TI - A multisystem investigation of raltegravir association with intestinal tissue:
implications for pre-exposure prophylaxis and eradication.
AB - OBJECTIVES: Recent clinical data have suggested high raltegravir concentrations
in gut tissue after oral administration, with implications for treatment and
prevention. We have used in silico, in vitro, ex vivo and in vivo models to
further investigate the accumulation of raltegravir in gut tissue. METHODS:
Affinity of raltegravir for gut tissue was assessed in silico (Poulin-Theil
method), in vitro (Caco-2 accumulation) and ex vivo (rat intestine) and compared
with the lipophilic drug lopinavir. Finally, raltegravir concentrations in
plasma, gut contents, small intestine and large intestine were determined after
oral dosing to Wistar rats 1 and 4 h post-dose. Samples were analysed using LC
MS/MS and scintillation counting. RESULTS: Gut tissue accumulation of raltegravir
was less than for lopinavir in silico, in vitro and ex vivo (P < 0.05). After
oral administration to rats, raltegravir concentrations 4 h post-dose were lower
in plasma (0.05 MUM) compared with small intestine (0.47 MUM, P = 0.06) and large
intestine (1.36 MUM, P < 0.05). However, raltegravir concentrations in the
contents of both small intestine (4.0 MUM) and large intestine (40.6 MUM) were
also high. CONCLUSIONS: In silico, in vitro and ex vivo data suggest low
raltegravir accumulation in intestinal tissue. In contrast, in vivo animal data
suggest raltegravir concentrates in intestinal tissue even when plasma
concentrations are minimal. However, high raltegravir concentrations in gut
contents are the likely driving factor behind this observation, rather than blood
to-tissue drug distribution. The methods described can be combined with clinical
investigations to provide a complete strategy for selection of drugs with high
gut accumulation.
PMID- 25114169
TI - Separation and quantification of 2-acyl-1-lysophospholipids and 1-acyl-2
lysophospholipids in biological samples by LC-MS/MS.
AB - Lysophospholipids (LysoGPs) serve as lipid mediators and precursors for synthesis
of diacyl phospholipids (GPs). LysoGPs detected in cells have various acyl chains
attached at either the sn-1 or sn-2 position of the glycerol backbone. In
general, acyl chains at the sn-2 position of 2-acyl-1-LysoGPs readily move to the
sn-1 position, generating 1-acyl-2-lyso isomers by a nonenzymatic reaction called
intra-molecular acyl migration, which has hampered the detection of 2-acyl-1
LysoGPs in biological samples. In this study, we developed a simple and versatile
method to separate and quantify 2-acyl-1- and 1-acyl-2-LysoGPs. The main point of
the method was to extract LysoGPs at pH 4 and 4 degrees C, conditions that were
found to completely eliminate the intra-molecular acyl migration. Under the
present conditions, the relative amounts of 2-acyl-1-LysoGPs and 1-acyl-2-LysoGPs
did not change at least for 1 week. Further, in LysoGPs extracted from cells and
tissues under the present conditions, most of the saturated fatty acids (16:0 and
18:0) were found in the sn-1 position of LysoGPs, while most of the PUFAs (18:2,
20:4, 22:6) were found in the sn-2 position. Thus the method can be used to
elucidate the in vivo role of 2-acyl-1-LysoGPs.
PMID- 25114170
TI - Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in the
liver.
AB - Acyl-CoA thioesterase (Acot)2 localizes to the mitochondrial matrix and
hydrolyses long-chain fatty acyl-CoA into free FA and CoASH. Acot2 is expressed
in highly oxi-dative tissues and is poised to modulate mitochondrial FA oxidation
(FAO), yet its biological role is unknown. Using a model of adenoviral Acot2
overexpression in mouse liver (Ad-Acot2), we show that Acot2 increases the
utilization of FA substrate during the daytime in ad libitum-fed mice, but the
nighttime switch to carbohydrate oxidation is similar to control mice. In further
support of elevated FAO in Acot2 liver, daytime serum ketones were higher in Ad
Acot2 mice, and overnight fasting led to minimal hepatic steatosis as compared
with control mice. In liver mitochondria from Ad-Acot2 mice, phosphorylating O2
consumption was higher with lipid substrate, but not with nonlipid substrate.
This increase depended on whether FA could be activated on the outer
mitochondrial membrane, suggesting that the FA released by Acot2 could be
effluxed from mitochondria then taken back up again for oxidation. This circuit
would prevent the build-up of inhibitory long-chain fatty acyl-CoA esters.
Altogether, our findings indicate that Acot2 can enhance FAO, possibly by
mitigating the accumulation of FAO intermediates within the mitochondrial matrix.
PMID- 25114173
TI - A reciprocal antagonism between miR-376c and TGF-beta signaling regulates neural
differentiation of human pluripotent stem cells.
AB - Differentiation of neural lineages from human pluripotent stem cells (hPSCs)
raises the hope of generating functional cells for the treatment of neural
diseases. However, current protocols for differentiating hPSCs into neural
lineages remain inefficient and largely variable between different hPSC lines. We
report that microRNA 376c (miR-376c) significantly enhanced neural
differentiation of hPSCs in a defined condition by suppressing SMAD4, the co-SMAD
for TGF-beta signaling. Downstream, SMAD4 directly bound and suppressed PAX6, the
critical neural lineage specification factor. Interestingly, we also found that
SMAD4 binds and suppresses miR-376c clusters in undifferentiated hESCs. In
summary, our findings revealed a reciprocal antagonism between miR-376c and SMAD
signaling that regulates cell fate during human neural differentiation.
PMID- 25114171
TI - Functional characterization of cytochrome P450-derived epoxyeicosatrienoic acids
in adipogenesis and obesity.
AB - Adipogenesis plays a critical role in the initiation and progression of obesity.
Although cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) have
emerged as a potential therapeutic target for cardiometabolic disease, the
functional contribution of EETs to adipogenesis and the pathogenesis of obesity
remain poorly understood. Our studies demonstrated that induction of adipogenesis
in differentiated 3T3-L1 cells (in vitro) and obesity-associated adipose
expansion in high-fat diet (HFD)-fed mice (in vivo) significantly dysregulate the
CYP epoxygenase pathway and evoke a marked suppression of adipose-derived EET
levels. Subsequent in vitro experiments demonstrated that exogenous EET analog
administration elicits potent anti-adipogenic effects via inhibition of the early
phase of adipogenesis. Furthermore, EET analog administration to mice
significantly mitigated HFD-induced weight gain, adipose tissue expansion, pro
adipogenic gene expression, and glucose intolerance. Collectively, these findings
suggest that suppression of EET bioavailability in adipose tissue is a key
pathological consequence of obesity, and strategies that promote the protective
effects of EETs in adipose tissue offer enormous therapeutic potential for
obesity and its downstream pathological consequences.
PMID- 25114174
TI - Exploration of salivary proteins in buffalo: an approach to find marker proteins
for estrus.
AB - Saliva is considered as the best source of biological material for biomarker
discovery studies since it is noninvasive in comparison to other body sources.
Usually buffalo cannot precisely express estrus signals. Hence, there is a need
for concise methods to detect the time of estrus to ensure the success of
artificial insemination. Therefore, we have established a reference proteome map
on the whole saliva of buffalo during their estrous cycle with special reference
to estrus. Nearly 12 bands have been observed using sodium dodecyl sulfate
polyacrylamide gel electrophoresis (SDS-PAGE) of whole saliva. Collectively, 179
proteins are identified with respect to different phases of the estrous cycle
using mass spectrometry. On the whole, 37 proteins are exclusively expressed in
the estrus phase, which include beta-enolase, Toll-like receptor (TLR) 4,
clusterin, lactoperoxidase, serotransferrin, TGM3, UBA6, and transducin. Among
the proteins, beta-enolase and TLR 4 were validated, and their specific
expression was found during estrus as compared to other phases using immunoblot.
The functional annotation reveals many as binding proteins in the estrus saliva
when compared to the other phases. The present findings conclude that the
proteomic approach adopted to identify the proteins from buffalo saliva around
the estrous cycle may provide a new tool for screening the estrus phase. The
results further conclude that the specific expression of beta-enolase and TLR 4
can be taken as the indicator of estrus in buffalo.
PMID- 25114172
TI - Adipose triglyceride lipase regulates eicosanoid production in activated human
mast cells.
AB - Human mast cells (MCs) contain TG-rich cytoplasmic lipid droplets (LDs) with high
arachidonic acid (AA) content. Here, we investigated the functional role of
adipose TG lipase (ATGL) in TG hydrolysis and the ensuing release of AA as
substrate for eicosanoid generation by activated human primary MCs in culture.
Silencing of ATGL in MCs by siRNAs induced the accumulation of neutral lipids in
LDs. IgE-dependent activation of MCs triggered the secretion of the two major
eicosanoids, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4). The immediate
release of PGD2 from the activated MCs was solely dependent on cyclooxygenase
(COX) 1, while during the delayed phase of lipid mediator production, the
inducible COX-2 also contributed to its release. Importantly, when ATGL-silenced
MCs were activated, the secretion of both PGD2 and LTC4 was significantly
reduced. Interestingly, the inhibitory effect on the release of LTC4 was even
more pronounced in ATGL-silenced MCs than in cytosolic phospholipase A2-silenced
MCs. These data show that ATGL hydrolyzes AA-containing TGs present in human MC
LDs and define ATGL as a novel regulator of the substrate availability of AA for
eicosanoid generation upon MC activation.
PMID- 25114175
TI - Structure of Toxoplasma gondii coronin, an actin-binding protein that relocalizes
to the posterior pole of invasive parasites and contributes to invasion and
egress.
AB - Coronins are involved in the regulation of actin dynamics in a multifaceted way,
participating in cell migration and vesicular trafficking. Apicomplexan
parasites, which exhibit an actin-dependent gliding motility that is essential
for traversal through tissues, as well as invasion of and egress from host cells,
express only a single coronin, whereas higher eukaryotes possess several
isoforms. We set out to characterize the 3-D structure, biochemical function,
subcellular localization, and genetic ablation of Toxoplasma gondii coronin
(TgCOR), to shed light on its biological role. A combination of X-ray
crystallography, small-angle scattering of X-rays, and light scattering revealed
the atomic structure of the conserved WD40 domain and the dimeric arrangement of
the full-length protein. TgCOR binds to F-actin and increases the rate and extent
of actin polymerization. In vivo, TgCOR relocalizes transiently to the posterior
pole of motile and invading parasites, independent of actin dynamics, but
concomitant to microneme secretory organelle discharge. TgCOR contributes to, but
is not essential for, invasion and egress. Taken together, our data point toward
a role for TgCOR in stabilizing newly formed, short filaments and F-actin cross
linking, as well as functions linked to endocytosis and recycling of membranes.
PMID- 25114176
TI - TRPV4, TRPC1, and TRPP2 assemble to form a flow-sensitive heteromeric channel.
AB - Transient receptor potential (TRP) channels, a superfamily of ion channels, can
be divided into 7 subfamilies, including TRPV, TRPC, TRPP, and 4 others.
Functional TRP channels are tetrameric complexes consisting of 4 pore-forming
subunits. The purpose of this study was to explore the heteromerization of TRP
subunits crossing different TRP subfamilies. Two-step coimmunoprecipitation (co
IP) and fluorescence resonance energy transfer (FRET) were used to determine the
interaction of the different TRP subunits. Patch-clamp and cytosolic Ca(2+)
measurements were used to determine the functional role of the ion channels in
flow conditions. The analysis demonstrated the formation of a heteromeric TRPV4
C1-P2 complex in primary cultured rat mesenteric artery endothelial cells (MAECs)
and HEK293 cells that were cotransfected with TRPV4, TRPC1, and TRPP2. In
functional experiments, pore-dead mutants for each of these 3 TRP isoforms nearly
abolished the flow-induced cation currents and Ca(2+) increase, suggesting that
all 3 TRPs contribute to the ion permeation pore of the channels. We identified
the first heteromeric TRP channels composed of subunits from 3 different TRP
subfamilies. Functionally, this heteromeric TRPV4-C1-P2 channel mediates the flow
induced Ca(2+) increase in native vascular endothelial cells.
PMID- 25114177
TI - A novel CRIg-targeted complement inhibitor protects cells from complement damage.
AB - The inappropriate activation of complement may contribute to various immune
diseases. The alternative pathway (AP) predominates during complement activation
regardless of the initiating pathways. Hence, the main AP regulator factor H (FH)
holds great potential as an attractive therapeutic intervention. In addition,
complement receptor of the immunoglobulin superfamily (CRIg) has been
demonstrated to inhibit AP and, more notably, still specifically binds to
C3b/iC3b. We thus developed novel CRIg-targeted complement inhibitors by
connecting the functional domains of CRIg and FH, which we termed CRIg-FH and
CRIg-L-FH. CRIg-L-FH, slightly more potent than CRIg-FH, considerably inhibited
both AP- and also classical pathway (CP)-mediated hemolysis and successfully
eliminated the deposition of C3b/iC3b. Kinetic analysis further revealed that the
binding affinity constant (KD) of CRIg/FH was in the micromolar range, consistent
with its long-lasting binding to complement-attacked cells. CRIg-L-FH efficiently
protected aberrant erythrocytes of patients with paroxysmal nocturnal
hemoglobinuria (PNH) from AP- and CP-mediated complement damage (IC50 was 22.43
and 64.69 nM, respectively). Moreover, CRIg-L-FH was found to inhibit complement
activation induced by the anti-Thy1 antibody in a mesangioproliferative
glomerulonephritis (MPGN) rat model. Hence, CRIg-L-FH protects glomerular
mesangial cells (GMCs) from complement-mediated injury and proliferative lesions.
These findings strongly suggest that CRIg/FH is a potential therapeutic drug
candidate for a range of complement-mediated diseases.
PMID- 25114178
TI - An intracellular antifreeze protein from an Antarctic microalga that responds to
various environmental stresses.
AB - The structure and function of the Antarctic marine diatom Chaetoceros neogracile
antifreeze protein (Cn-AFP), as well as its expression levels and characteristics
of the ice-binding site, were analyzed in the present study. In silico analysis
revealed that the Cn-AFP promoter contains both light- and temperature-responsive
elements. Northern and Western blot analyses demonstrated that both Cn-AFP
transcript and protein expression were strongly and rapidly stimulated by
freezing, as well as temperature and high light stress. Immunogold labeling
revealed that Cn-AFP is preferentially localized to the intracellular space near
the chloroplast membrane. Recombinant Cn-AFP had clear antifreeze activity.
Protein-folding simulation was used to predict the putative ice-binding sites in
Cn-AFP, and site-directed mutagenesis of the Cn-AFP b-face confirmed their
identification.
PMID- 25114179
TI - Functional and structural characterization of the kinase insert and the carboxy
terminal domain in VEGF receptor 2 activation.
AB - Vascular endothelial growth factors (VEGFs) regulate blood and lymphatic vessel
development and homeostasis. VEGF receptor 2 (VEGFR-2) is the major receptor
involved in vasculogenesis and angiogenesis and regulates endothelial cell
survival, migration, and mitogenesis. Ligand-mediated receptor dimerization
instigates transmembrane signaling, thereby promoting activation of the
intracellular kinase domain. The intracellular part of the receptor comprises the
juxtamembrane domain, the catalytic kinase domain, the kinase insert domain
(KID), and the carboxy terminal domain (CD). Here we show that the CD inhibits
VEGFR-2 activity in the absence of ligand, whereas the KID, particularly a
tyrosine residue in this domain (Y951), is indispensable for downstream signaling
by the activated kinase. Because of the lack of crystallographic data for the
complete kinase domain, we applied size-exclusion chromatography, multiangle
laser scattering, analytical ultracentrifugation, and small-angle X-ray
scattering to build and functionally validate structural models. Our data show
substantial conformational changes of the kinase when it is switched from the
inactive, unphosphorylated state to the active, phosphorylated state. Finally, we
structurally characterized recombinantly produced protein complexes between VEGFR
2 and T cell-specific adapter protein, a molecule involved in downstream
signaling by VEGFR-2.
PMID- 25114180
TI - Inducible factors with antimicrobial activity after immune challenge in the
haemolymph of Red Palm Weevil (Insecta).
AB - Insects are capable of innate immune responses elicited after microbial
infection. In this process, the receptor-mediated recognition of foreign bodies
and the subsequent activation of immunocompetent cells lead to the synthesis ex
novo of a peptide pool with antimicrobial activity. We investigated the inducible
immune response of a coleopteran, Rhynchophorus ferrugineus, challenged with both
Gram-negative and Gram-positive bacteria. After immunization, we evaluated the
presence of antimicrobial peptides using either biochemical analyses or
microbiological techniques. The antimicrobial properties of the newly synthesized
protein pool, detectable in haemolymph fractions of low molecular mass, showed
strong antibacterial activity against various bacterial strains (Escherichia
coli, Pseudomonas sp. OX1, Bacillus subtilis and Micrococcus luteus). In addition
to the preliminary study of the mechanism of action of the pool of antimicrobial
peptides, we also investigated its effects on bacterial cell walls by means of
fluorescence microscopy and scanning electron microscopy. The data suggest that
the main effects seem to be directed at destabilizing and damaging the bacterial
wall. This study provides data that help us to understand some aspects of the
inducible innate immunity in a system model that lacks anticipatory responses.
However, the weevil has finely tuned its defensive strategies to counteract
effectively microbial infection.
PMID- 25114181
TI - The IOC Centres of Excellence bring prevention to sports medicine.
AB - The protection of an athlete's health and preventing injuries and illnesses in
sport are top priorities for the IOC and its Medical Commission. The IOC
therefore partners with selected research centres around the world and supports
research in the field of sports medicine. This has enabled the IOC to develop an
international network of expert scientists and clinicians in sports injury and
disease prevention research. The IOC wants to promote injury and disease
prevention and the improvement of physical health of the athlete by: (1)
establishing long-term research programmes on injury and disease prevention
(including studies on basic epidemiology, risk factors, injury mechanisms and
intervention), (2) fostering collaborative relationships with individuals,
institutions and organisations to improve athletes' health, (3) implementing and
collaborating with applied, ongoing and novel research and development within the
framework and long-term strategy of the IOC and (4) setting up knowledge
translation mechanisms to share scientific research results with the field
throughout the Olympic Movement and sports community and converting these results
into concrete actions to protect the health of the athletes. In 2009, the IOC
also identified four research centres that had an established track record in
research, educational and clinical activities to achieve these ambitions: (1) the
Australian Centre for Research into Injury in Sport and its Prevention (ACRISP),
Australia; (2) the Sport Injury Prevention Research Centre (SIPRC), Canada; (3)
the Clinical Sport and Exercise Medicine Research (CSEM), South Africa and (4)
the Oslo Sports Trauma Research Center (OSTRC), Norway. This paper highlights the
work carried out by these four IOC Centres of Excellence over the past 6 years
and their contribution to the world of sports medicine.
PMID- 25114183
TI - Republished research: Impact of autologous blood injections in treatment of mid
portion Achilles tendinopathy: double blind randomised controlled trial.
AB - STUDY QUESTION: Do peritendinous autologous blood injections improve pain and
function in people with mid-portion Achilles tendinopathy? SUMMARY ANSWER: The
administration of two unguided peritendinous autologous blood injections one
month apart, in addition to a standardised eccentric training programme, provides
no additional benefit in the treatment of mid-portion Achilles tendinopathy. WHAT
IS KNOWN AND WHAT THIS PAPER ADDS: Several studies have suggested that injection
of autologous blood can help in the treatment of various tendinopathies. There is
a lack of high quality evidence showing relevant benefit for autologous blood
injections, particularly in the management of mid-portion Achilles tendinopathy.
We found no additional reduction in pain or improvement in function when these
injections were combined with an eccentric calf training programme.
PMID- 25114184
TI - Extensive blueberry muffin rash in a neonate.
PMID- 25114185
TI - The current status of neonatal organ donation in the UK.
PMID- 25114187
TI - Varicose veins.
PMID- 25114186
TI - Novel wireless devices for cardiac monitoring.
PMID- 25114188
TI - ECG Response: August 12, 2014.
PMID- 25114190
TI - Pseudo-pre-excitation unraveled down to its core.
PMID- 25114189
TI - Left ventricular hypertrophy in a runner: things are not always what they seem.
PMID- 25114191
TI - Cardiology patient page. Varicose veins.
PMID- 25114192
TI - Letter by Takahashi regarding article "targeting interleukin-1 in heart disease".
PMID- 25114193
TI - Response to letter regarding article, "targeting interleukin-1 in heart disease".
PMID- 25114197
TI - Neurology in Africa.
PMID- 25114196
TI - In vitro and in vivo evaluation of a novel collagen/cellulose nanocrystals
scaffold for achieving the sustained release of basic fibroblast growth factor.
AB - Tissue-engineered dermis is thought to be the best treatment for skin defects;
however, slow vascularization of these biomaterial scaffolds limits their
clinical application. Exogenous administration of angiogenic growth factors is
highly desirable for tissue regeneration. In this study, biodegradable gelatin
microspheres (GMs) containing basic fibroblast growth factor (bFGF) were
fabricated and incorporated into a porous collagen/cellulose nanocrystals (CNCs)
scaffold, as a platform for long-term release and consequent angiogenic boosting.
The physicochemical properties of these scaffolds were examined and the in vitro
release pattern of bFGF from scaffolds was measured by ELISA. Collagen/CNCs
scaffolds with and without bFGF-GMs were incubated with human umbilical vein
endothelial cells for 1 week, results showed that the scaffolds with bFGF-GMs
significantly augmented cell proliferation. Then, four different groups of
scaffolds were implanted subcutaneously into Sprague-Dawley rats to study
angiogenesis in vivo via macroscopic observation, and hematoxylin and eosin and
immunohistochemical staining. The results suggested that the collagen/CNCs/bFGF
GMs scaffolds had a significantly higher number of newly formed and mature blood
vessels, and the fastest degradation rate. This study demonstrated that
collagen/CNCs/bFGF-GMs scaffolds have great potential in skin tissue engineering.
PMID- 25114198
TI - Inflammatory neurologic disease in sub-Saharan Africa.
PMID- 25114199
TI - Prune belly and schizencephaly.
PMID- 25114200
TI - Wrong side dilated pupil.
PMID- 25114201
TI - Clinical Reasoning: An unusual cause of transverse myelitis?
PMID- 25114203
TI - Clinical Reasoning: A 38-year-old woman with childhood-onset weakness.
PMID- 25114204
TI - Teaching NeuroImages: Infantile herpes simplex encephalitis.
PMID- 25114205
TI - Teaching NeuroImages: Ocular bruit in carotid-cavernous sinus fistula.
PMID- 25114206
TI - Recent research on the growth plate: Advances in fibroblast growth factor
signaling in growth plate development and disorders.
AB - Skeletons are formed through two distinct developmental actions, intramembranous
ossification and endochondral ossification. During embryonic development, most
bone is formed by endochondral ossification. The growth plate is the
developmental center for endochondral ossification. Multiple signaling pathways
participate in the regulation of endochondral ossification. Fibroblast growth
factor (FGF)/FGF receptor (FGFR) signaling has been found to play a vital role in
the development and maintenance of growth plates. Missense mutations in FGFs and
FGFRs can cause multiple genetic skeletal diseases with disordered endochondral
ossification. Clarifying the molecular mechanisms of FGFs/FGFRs signaling in
skeletal development and genetic skeletal diseases will have implications for the
development of therapies for FGF-signaling-related skeletal dysplasias and growth
plate injuries. In this review, we summarize the recent advances in elucidating
the role of FGFs/FGFRs signaling in growth plate development, genetic skeletal
disorders, and the promising therapies for those genetic skeletal diseases
resulting from FGFs/FGFRs dysfunction. Finally, we also examine the potential
important research in this field in the future.
PMID- 25114207
TI - Recent research on the growth plate: Mechanisms for growth plate injury repair
and potential cell-based therapies for regeneration.
AB - Injuries to the growth plate cartilage often lead to bony repair, resulting in
bone growth defects such as limb length discrepancy and angulation deformity in
children. Currently utilised corrective surgeries are highly invasive and limited
in their effectiveness, and there are no known biological therapies to induce
cartilage regeneration and prevent the undesirable bony repair. In the last 2
decades, studies have investigated the cellular and molecular events that lead to
bony repair at the injured growth plate including the identification of the four
phases of injury repair responses (inflammatory, fibrogenic, osteogenic and
remodelling), the important role of inflammatory cytokine tumour necrosis factor
alpha in regulating downstream repair responses, the role of chemotactic and
mitogenic platelet-derived growth factor in the fibrogenic response, the
involvement and roles of bone morphogenic protein and Wnt/B-catenin signalling
pathways, as well as vascular endothelial growth factor-based angiogenesis during
the osteogenic response. These new findings could potentially lead to
identification of new targets for developing a future biological therapy. In
addition, recent advances in cartilage tissue engineering highlight the promising
potential for utilising multipotent mesenchymal stem cells (MSCs) for inducing
regeneration of injured growth plate cartilage. This review aims to summarise
current understanding of the mechanisms for growth plate injury repair and
discuss some progress, potential and challenges of MSC-based therapies to induce
growth plate cartilage regeneration in combination with chemotactic and
chondrogenic growth factors and supporting scaffolds.
PMID- 25114208
TI - Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from
the American Heart Association and American Diabetes Association.
PMID- 25114209
TI - Murine CD27(-) Vgamma6(+) gammadelta T cells producing IL-17A promote ovarian
cancer growth via mobilization of protumor small peritoneal macrophages.
AB - Cancer-associated inflammation mobilizes a variety of leukocyte populations that
can inhibit or enhance tumor cell growth in situ. These subsets include
gammadelta T cells, which can infiltrate tumors and typically provide large
amounts of antitumor cytokines, such as IFN-gamma. By contrast, we report here
that in a well-established transplantable (ID8 cell line) model of
peritoneal/ovarian cancer, gammadelta T cells promote tumor cell growth.
gammadelta T cells accumulated in the peritoneal cavity in response to tumor
challenge and could be visualized within solid tumor foci. Functional
characterization of tumor-associated gammadelta T cells revealed preferential
production of interleukin-17A (IL-17), rather than IFN-gamma. Consistent with
this finding, both T cell receptor (TCR)delta-deficient and IL-17-deficient mice
displayed reduced ID8 tumor growth compared with wild-type animals. IL-17
production by gammadelta T cells in the tumor environment was essentially
restricted to a highly proliferative CD27((-)) subset that expressed Vgamma6
instead of the more common Vgamma1 and Vgamma4 TCR chains. The preferential
expansion of IL-17-secreting CD27((-)) Vgamma6((+)) gammadelta T cells associated
with the selective mobilization of unconventional small peritoneal macrophages
(SPMs) that, in comparison with large peritoneal macrophages, were enriched for
IL-17 receptor A, and for protumor and proangiogenic molecular mediators, which
were up-regulated by IL-17. Importantly, SPMs were uniquely and directly capable
of promoting ovarian cancer cell proliferation. Collectively, this work
identifies an IL-17-dependent lymphoid/myeloid cross-talk involving gammadelta T
cells and SPMs that promotes tumor cell growth and thus counteracts cancer
immunosurveillance.
PMID- 25114212
TI - Modeling morphological diversity in the oldest large multicellular organisms.
PMID- 25114210
TI - Characterizing the proton loading site in cytochrome c oxidase.
AB - Cytochrome c oxidase (CcO) uses the energy released by reduction of O2 to H2O to
drive eight charges from the high pH to low pH side of the membrane, increasing
the electrochemical gradient. Four electrons and protons are used for chemistry,
while four more protons are pumped. Proton pumping requires that residues on a
pathway change proton affinity through the reaction cycle to load and then
release protons. The protonation states of all residues in CcO are determined in
MultiConformational Continuum Electrostatics simulations with the protonation and
redox states of heme a, a3, Cu(B), Y288, and E286 used to define the catalytic
cycle. One proton is found to be loaded and released from residues identified as
the proton loading site (PLS) on the P-side of the protein in each of the four
CcO redox states. Thus, the same proton pumping mechanism can be used each time
CcO is reduced. Calculations with structures of Rhodobacter sphaeroides,
Paracoccus denitrificans, and bovine CcO derived by crystallography and molecular
dynamics show the PLS functions similarly in different CcO species. The PLS is a
cluster rather than a single residue, as different structures show 1-4 residues
load and release protons. However, the proton affinity of the heme a3 propionic
acids primarily determines the number of protons loaded into the PLS; if their
proton affinity is too low, less than one proton is loaded.
PMID- 25114211
TI - Mapping of SUMO sites and analysis of SUMOylation changes induced by external
stimuli.
AB - SUMOylation is an essential ubiquitin-like modification involved in important
biological processes in eukaryotic cells. Identification of small ubiquitin
related modifier (SUMO)-conjugated residues in proteins is critical for
understanding the role of SUMOylation but remains experimentally challenging. We
have set up a powerful and high-throughput method combining quantitative
proteomics and peptide immunocapture to map SUMOylation sites and have analyzed
changes in SUMOylation in response to stimuli. With this technique we identified
295 SUMO1 and 167 SUMO2 sites on endogenous substrates of human cells. We further
used this strategy to characterize changes in SUMOylation induced by
listeriolysin O, a bacterial toxin that impairs the host cell SUMOylation
machinery, and identified several classes of host proteins specifically
deSUMOylated in response to this toxin. Our approach constitutes an unprecedented
tool, broadly applicable to various SUMO-regulated cellular processes in health
and disease.
PMID- 25114213
TI - Vectored antibody gene delivery protects against Plasmodium falciparum sporozoite
challenge in mice.
AB - Malaria caused by Plasmodium falciparum kills nearly one million children each
year and imposes crippling economic burdens on families and nations worldwide. No
licensed vaccine exists, but infection can be prevented by antibodies against the
circumsporozoite protein (CSP), the major surface protein of sporozoites, the
form of the parasite injected by mosquitoes. We have used vectored
immunoprophylaxis (VIP), an adeno-associated virus-based technology, to introduce
preformed antibody genes encoding anti-P. falciparum CSP mAb into mice. VIP
vector-transduced mice exhibited long-lived mAb expression at up to 1,200 ug/mL
in serum, and up to 70% were protected from both i.v. and mosquito bite challenge
with transgenic Plasmodium berghei rodent sporozoites that incorporate the P.
falciparum target of the mAb in their CSP. Serum antibody levels and protection
from mosquito bite challenge were dependent on the dose of the VIP vector. All
individual mice expressing CSP-specific mAb 2A10 at 1 mg/mL or more were
completely protected, suggesting that in this model system, exceeding that
threshold results in consistent sterile protection. Our results demonstrate the
potential of VIP as a path toward the elusive goal of immunization against
malaria.
PMID- 25114214
TI - Rare earth elements activate endocytosis in plant cells.
AB - It has long been observed that rare earth elements (REEs) regulate multiple
facets of plant growth and development. However, the underlying mechanisms remain
largely unclear. Here, using electron microscopic autoradiography, we show the
life cycle of a light REE (lanthanum) and a heavy REE (terbium) in horseradish
leaf cells. Our data indicate that REEs were first anchored on the plasma
membrane in the form of nanoscale particles, and then entered the cells by
endocytosis. Consistently, REEs activated endocytosis in plant cells, which may
be the cellular basis of REE actions in plants. Moreover, we discovered that a
portion of REEs was successively released into the cytoplasm, self-assembled to
form nanoscale clusters, and finally deposited in horseradish leaf cells. Taken
together, our data reveal the life cycle of REEs and their cellular behaviors in
plant cells, which shed light on the cellular mechanisms of REE actions in living
organisms.
PMID- 25114215
TI - Wnt ligand/Frizzled 2 receptor signaling regulates tube shape and branch-point
formation in the lung through control of epithelial cell shape.
AB - Changing the morphology of a simple epithelial tube to form a highly ramified
branching network requires changes in cell behavior that lead to tissue-wide
changes in organ shape. How epithelial cells in branched organs modulate their
shape and behavior to promote bending and sculpting of the epithelial sheet is
not well understood, and the mechanisms underlying this process remain obscure.
We show that the Wnt receptor Frizzled 2 (Fzd2) is required for domain branch
formation during the initial establishment of the respiratory tree. Live imaging
and transcriptome analysis of lung-branching morphogenesis demonstrate that Fzd2
promotes changes in epithelial cell length and shape. These changes in cell
morphology deform the developing epithelial tube to generate and maintain new
domain branches. Fzd2 controls branch formation and the shape of the epithelial
tube by regulating Rho signaling and by the localization of phospho-myosin light
chain 2, in turn controlling the changes in the shape of epithelial cells during
morphogenesis. This study demonstrates the importance of Wnt/Fzd2 signaling in
promoting and maintaining changes in epithelial cell shape that affect
development of a branching network.
PMID- 25114217
TI - Natural selection drives the evolution of ant life cycles.
AB - The genetic origin of advanced social organization has long been one of the
outstanding problems of evolutionary biology. Here we present an analysis of the
major steps in ant evolution, based for the first time, to our knowledge, on
combined recent advances in paleontology, phylogeny, and the study of
contemporary life histories. We provide evidence of the causal forces of natural
selection shaping several key phenomena: (i) the relative lateness and rarity in
geological time of the emergence of eusociality in ants and other animal phylads;
(ii) the prevalence of monogamy at the time of evolutionary origin; and (iii) the
female-biased sex allocation observed in many ant species. We argue that a clear
understanding of the evolution of social insects can emerge if, in addition to
relatedness-based arguments, we take into account key factors of natural history
and study how natural selection acts on alleles that modify social behavior.
PMID- 25114216
TI - Enhanced killing of antibiotic-resistant bacteria enabled by massively parallel
combinatorial genetics.
AB - New therapeutic strategies are needed to treat infections caused by drug
resistant bacteria, which constitute a major growing threat to human health.
Here, we use a high-throughput technology to identify combinatorial genetic
perturbations that can enhance the killing of drug-resistant bacteria with
antibiotic treatment. This strategy, Combinatorial Genetics En Masse (CombiGEM),
enables the rapid generation of high-order barcoded combinations of genetic
elements for high-throughput multiplexed characterization based on next
generation sequencing. We created ~ 34,000 pairwise combinations of Escherichia
coli transcription factor (TF) overexpression constructs. Using Illumina
sequencing, we identified diverse perturbations in antibiotic-resistance
phenotypes against carbapenem-resistant Enterobacteriaceae. Specifically, we
found multiple TF combinations that potentiated antibiotic killing by up to 10(6)
fold and delivered these combinations via phagemids to increase the killing of
highly drug-resistant E. coli harboring New Delhi metallo-beta-lactamase-1.
Moreover, we constructed libraries of three-wise combinations of transcription
factors with >4 million unique members and demonstrated that these could be
tracked via next-generation sequencing. We envision that CombiGEM could be
extended to other model organisms, disease models, and phenotypes, where it could
accelerate massively parallel combinatorial genetics studies for a broad range of
biomedical and biotechnology applications, including the treatment of antibiotic
resistant infections.
PMID- 25114219
TI - Demography, not inheritance, drives phenotypic change in hunted bighorn sheep.
AB - Selective harvest, such as trophy hunting, can shift the distribution of a
quantitative character such as body size. If the targeted character is heritable,
then there will be an evolutionary response to selection, and where the trait is
not, then any response will be plastic or demographic. Identifying the relative
contributions of these different mechanisms is a major challenge in wildlife
conservation. New mathematical approaches can provide insight not previously
available. Here we develop a size- and age-based two-sex integral projection
model based on individual-based data from a long-term study of hunted bighorn
sheep (Ovis canadensis) at Ram Mountain, Canada. We simulate the effect of trophy
hunting on body size and find that the inheritance of body mass is weak and that
any perceived decline in body mass of the bighorn population is largely
attributable to demographic change and environmental factors. To our knowledge,
this work provides the first use of two-sex integral projection models to
investigate the potential eco-evolutionary consequences of selective harvest.
PMID- 25114218
TI - Primary cilia are required in a unique subpopulation of neural progenitors.
AB - The apical domain of embryonic (radial glia) and adult (B1 cells) neural stem
cells (NSCs) contains a primary cilium. This organelle has been suggested to
function as an antenna for the detection of morphogens or growth factors. In
particular, primary cilia are essential for Hedgehog (Hh) signaling, which plays
key roles in brain development. Their unique location facing the ventricular
lumen suggests that primary cilia in NSCs could play an important role in
reception of signals within the cerebrospinal fluid. Surprisingly, ablation of
primary cilia using conditional alleles for genes essential for intraflagellar
transport [kinesin family member 3A (Kif3a) and intraflagellar transport 88
(Ift88)] and Cre drivers that are activated at early [Nestin; embryonic day 10.5
(E10.5)] and late [human glial fibrillary acidic protein (hGFAP); E13.5] stages
of mouse neural development resulted in no apparent developmental defects.
Neurogenesis in the ventricular-subventricular zone (V-SVZ) shortly after birth
was also largely unaffected, except for a restricted ventral domain previously
known to be regulated by Hh signaling. However, Kif3a and Ift88 genetic ablation
also disrupts ependymal cilia, resulting in hydrocephalus by postnatal day 4. To
directly study the role of B1 cells' primary cilia without the confounding
effects of hydrocephalus, we stereotaxically targeted elimination of Kif3a from a
subpopulation of radial glia, which resulted in ablation of primary cilia in a
subset of B1 cells. Again, this experiment resulted in decreased neurogenesis
only in the ventral V-SVZ. Primary cilia ablation led to disruption of Hh
signaling in this subdomain. We conclude that primary cilia are required in a
specific Hh-regulated subregion of the postnatal V-SVZ.
PMID- 25114220
TI - Autophagy protects C. elegans against necrosis during Pseudomonas aeruginosa
infection.
AB - Autophagy, a conserved pathway that delivers intracellular materials into
lysosomes for degradation, is involved in development, aging, and a variety of
diseases. Accumulating evidence demonstrates that autophagy plays a protective
role against infectious diseases by diminishing intracellular pathogens,
including bacteria, viruses, and parasites. However, the mechanism by which
autophagy regulates innate immunity remains largely unknown. Here, we show that
autophagy is involved in host defense against a pathogenic bacterium Pseudomonas
aeruginosa in the metazoan Caenorhabditis elegans. P. aeruginosa infection
induces autophagy via a conserved extracellular signal-regulated kinase (ERK).
Intriguingly, impairment of autophagy does not influence the intestinal
accumulation of P. aeruginosa, but instead induces intestinal necrosis.
Inhibition of necrosis results in the survival of autophagy-deficient worms after
P. aeruginosa infection. These findings reveal a previously unidentified role for
autophagy in protection against necrosis triggered by pathogenic bacteria in C.
elegans and implicate that such a function of autophagy may be conserved through
the inflammatory response in diverse organisms.
PMID- 25114221
TI - Inhibitor of MYC identified in a Krohnke pyridine library.
AB - In a fluorescence polarization screen for the MYC-MAX interaction, we have
identified a novel small-molecule inhibitor of MYC, KJ-Pyr-9, from a Krohnke
pyridine library. The Kd of KJ-Pyr-9 for MYC in vitro is 6.5 +/- 1.0 nM, as
determined by backscattering interferometry; KJ-Pyr-9 also interferes with MYC
MAX complex formation in the cell, as shown in a protein fragment complementation
assay. KJ-Pyr-9 specifically inhibits MYC-induced oncogenic transformation in
cell culture; it has no or only weak effects on the oncogenic activity of several
unrelated oncoproteins. KJ-Pyr-9 preferentially interferes with the proliferation
of MYC-overexpressing human and avian cells and specifically reduces the MYC
driven transcriptional signature. In vivo, KJ-Pyr-9 effectively blocks the growth
of a xenotransplant of MYC-amplified human cancer cells.
PMID- 25114222
TI - Tumorigenicity of hypoxic respiring cancer cells revealed by a hypoxia-cell cycle
dual reporter.
AB - Although aerobic glycolysis provides an advantage in the hypoxic tumor
microenvironment, some cancer cells can also respire via oxidative
phosphorylation. These respiring ("non-Warburg") cells were previously thought
not to play a key role in tumorigenesis and thus fell from favor in the
literature. We sought to determine whether subpopulations of hypoxic cancer cells
have different metabolic phenotypes and gene-expression profiles that could
influence tumorigenicity and therapeutic response, and we therefore developed a
dual fluorescent protein reporter, HypoxCR, that detects hypoxic [hypoxia
inducible factor (HIF) active] and/or cycling cells. Using HEK293T cells as a
model, we identified four distinct hypoxic cell populations by flow cytometry.
The non-HIF/noncycling cell population expressed a unique set of genes involved
in mitochondrial function. Relative to the other subpopulations, these hypoxic
"non-Warburg" cells had highest oxygen consumption rates and mitochondrial
capacity consistent with increased mitochondrial respiration. We found that these
respiring cells were unexpectedly tumorigenic, suggesting that continued
respiration under limiting oxygen conditions may be required for tumorigenicity.
PMID- 25114224
TI - Predicting hybrid performance in rice using genomic best linear unbiased
prediction.
AB - Genomic selection is an upgrading form of marker-assisted selection for
quantitative traits, and it differs from the traditional marker-assisted
selection in that markers in the entire genome are used to predict genetic values
and the QTL detection step is skipped. Genomic selection holds the promise to be
more efficient than the traditional marker-assisted selection for traits
controlled by polygenes. Genomic selection for pure breed improvement is based on
marker information and thus leads to cost-saving due to early selection before
phenotypes are measured. When applied to hybrid breeding, genomic selection is
anticipated to be even more efficient because genotypes of hybrids are
predetermined by their inbred parents. Hybrid breeding has been an important tool
to increase crop productivity. Here we proposed and applied an advanced method to
predict hybrid performance, in which a subset of all potential hybrids is used as
a training sample to predict trait values of all potential hybrids. The method is
called genomic best linear unbiased prediction. The technology applied to hybrids
is called genomic hybrid breeding. We used 278 randomly selected hybrids derived
from 210 recombinant inbred lines of rice as a training sample and predicted all
21,945 potential hybrids. The average yield of top 100 selection shows a 16%
increase compared with the average yield of all potential hybrids. The new
strategy of marker-guided prediction of hybrid yields serves as a proof of
concept for a new technology that may potentially revolutionize hybrid breeding.
PMID- 25114225
TI - Drought stress variability in ancient Near Eastern agricultural systems evidenced
by delta13C in barley grain.
AB - The collapse and resilience of political systems in the ancient Near East and
their relationship with agricultural development have been of wide interest in
archaeology and anthropology. Despite attempts to link the archaeological
evidence to local paleoclimate data, the precise role of environmental conditions
in ancient agricultural production remains poorly understood. Recently, stable
isotope analysis has been used for reconstructing site-specific ancient growing
conditions for crop species in semiarid and arid landscapes. To open the
discussion of the role of regional diversity in past agricultural production as a
factor in societal development, we present 1.037 new stable carbon isotope
measurements from 33 archaeological sites and modern fields in the geographic
area of the Fertile Crescent, spanning the Aceramic Neolithic [10,000 calibrated
years (cal) B.C.] to the later Iron Age (500 cal B.C.), alongside modern data
from 13 locations. Our data show that drought stress was an issue in many
agricultural settlements in the ancient Near East, particularly in correlation
with the major Holocene climatic fluctuations, but its regional impact was
diverse and influenced by geographic factors. Although cereals growing in the
coastal areas of the northern Levant were relatively unaffected by Holocene
climatic fluctuations, farmers of regions further inland had to apply irrigation
to cope with increased water stress. However, inland agricultural strategies
showed a high degree of variability. Our findings suggest that regional
differences in climatic effects led to diversified strategies in ancient
subsistence and economy even within spatially limited cultural units.
PMID- 25114223
TI - Small-molecule screening identifies inhibition of salt-inducible kinases as a
therapeutic strategy to enhance immunoregulatory functions of dendritic cells.
AB - Genetic alterations that reduce the function of the immunoregulatory cytokine IL
10 contribute to colitis in mouse and man. Myeloid cells such as macrophages
(MPhis) and dendritic cells (DCs) play an essential role in determining the
relative abundance of IL-10 versus inflammatory cytokines in the gut. As such,
using small molecules to boost IL-10 production by DCs-MPhis represents a
promising approach to increase levels of this cytokine specifically in gut
tissues. Toward this end, we screened a library of well-annotated kinase
inhibitors for compounds that enhance production of IL-10 by murine bone-marrow
derived DCs stimulated with the yeast cell wall preparation zymosan. This
approach identified a number of kinase inhibitors that robustly up-regulate IL-10
production including the Food and Drug Administration (FDA)-approved drugs
dasatinib, bosutinib, and saracatinib that target ABL, SRC-family, and numerous
other kinases. Correlating the kinase selectivity profiles of the active
compounds with their effect on IL-10 production suggests that inhibition of salt
inducible kinases (SIKs) mediates the observed IL-10 increase. This was confirmed
using the SIK-targeting inhibitor HG-9-91-01 and a series of structural analogs.
The stimulatory effect of SIK inhibition on IL-10 is also associated with
decreased production of the proinflammatory cytokines IL-1beta, IL-6, IL-12, and
TNF-alpha, and these coordinated effects are observed in human DCs-MPhis and anti
inflammatory CD11c(+) CX3CR1(hi) cells isolated from murine gut tissue.
Collectively, these studies demonstrate that SIK inhibition promotes an anti
inflammatory phenotype in activated myeloid cells marked by robust IL-10
production and establish these effects as a previously unidentified activity
associated with several FDA-approved multikinase inhibitors.
PMID- 25114226
TI - MRI-localized biopsies reveal subtype-specific differences in molecular and
cellular composition at the margins of glioblastoma.
AB - Glioblastomas (GBMs) diffusely infiltrate the brain, making complete removal by
surgical resection impossible. The mixture of neoplastic and nonneoplastic cells
that remain after surgery form the biological context for adjuvant therapeutic
intervention and recurrence. We performed RNA-sequencing (RNA-seq) and
histological analysis on radiographically guided biopsies taken from different
regions of GBM and showed that the tissue contained within the contrast-enhancing
(CE) core of tumors have different cellular and molecular compositions compared
with tissue from the nonenhancing (NE) margins of tumors. Comparisons with the
The Cancer Genome Atlas dataset showed that the samples from CE regions resembled
the proneural, classical, or mesenchymal subtypes of GBM, whereas the samples
from the NE regions predominantly resembled the neural subtype. Computational
deconvolution of the RNA-seq data revealed that contributions from nonneoplastic
brain cells significantly influence the expression pattern in the NE samples.
Gene ontology analysis showed that the cell type-specific expression patterns
were functionally distinct and highly enriched in genes associated with the
corresponding cell phenotypes. Comparing the RNA-seq data from the GBM samples to
that of nonneoplastic brain revealed that the differentially expressed genes are
distributed across multiple cell types. Notably, the patterns of cell type
specific alterations varied between the different GBM subtypes: the NE regions of
proneural tumors were enriched in oligodendrocyte progenitor genes, whereas the
NE regions of mesenchymal GBM were enriched in astrocytic and microglial genes.
These subtype-specific patterns provide new insights into molecular and cellular
composition of the infiltrative margins of GBM.
PMID- 25114228
TI - Synchronization in human musical rhythms and mutually interacting complex
systems.
AB - Though the music produced by an ensemble is influenced by multiple factors,
including musical genre, musician skill, and individual interpretation, rhythmic
synchronization is at the foundation of musical interaction. Here, we study the
statistical nature of the mutual interaction between two humans synchronizing
rhythms. We find that the interbeat intervals of both laypeople and professional
musicians exhibit scale-free (power law) cross-correlations. Surprisingly, the
next beat to be played by one person is dependent on the entire history of the
other person's interbeat intervals on timescales up to several minutes. To
understand this finding, we propose a general stochastic model for mutually
interacting complex systems, which suggests a physiologically motivated
explanation for the occurrence of scale-free cross-correlations. We show that the
observed long-term memory phenomenon in rhythmic synchronization can be imitated
by fractal coupling of separately recorded or synthesized audio tracks and thus
applied in electronic music. Though this study provides an understanding of
fundamental characteristics of timing and synchronization at the interbrain
level, the mutually interacting complex systems model may also be applied to
study the dynamics of other complex systems where scale-free cross-correlations
have been observed, including econophysics, physiological time series, and
collective behavior of animal flocks.
PMID- 25114227
TI - Nicotinic and muscarinic agonists and acetylcholinesterase inhibitors stimulate a
common pathway to enhance GluN2B-NMDAR responses.
AB - Nicotinic and muscarinic ACh receptor agonists and acetylcholinesterase
inhibitors (AChEIs) can enhance cognitive function. However, it is unknown
whether a common signaling pathway is involved in the effect. Here, we show that
in vivo administration of nicotine, AChEIs, and an m1 muscarinic (m1) agonist
increase glutamate receptor, ionotropic, N-methyl D-aspartate 2B (GluN2B)
containing NMDA receptor (NR2B-NMDAR) responses, a necessary component in memory
formation, in hippocampal CA1 pyramidal cells, and that coadministration of the
m1 antagonist pirenzepine prevents the effect of cholinergic drugs. These
observations suggest that the effect of nicotine is secondary to increased
release of ACh via the activation of nicotinic ACh receptors (nAChRs) and
involves m1 receptor activation through ACh. In vitro activation of m1 receptors
causes the selective enhancement of NR2B-NMDAR responses in CA1 pyramidal cells,
and in vivo exposure to cholinergic drugs occludes the in vitro effect.
Furthermore, in vivo exposure to cholinergic drugs suppresses the potentiating
effect of Src on NMDAR responses in vitro. These results suggest that exposure to
cholinergic drugs maximally stimulates the m1/guanine nucleotide-binding protein
subunit alpha q/PKC/proline-rich tyrosine kinase 2/Src signaling pathway for the
potentiation of NMDAR responses in vivo, occluding the in vitro effects of m1
activation and Src. Thus, our results indicate not only that nAChRs, ACh, and m1
receptors are on the same pathway involving Src signaling but also that NR2B
NMDARs are a point of convergence of cholinergic and glutamatergic pathways
involved in learning and memory.
PMID- 25114229
TI - Profile of Alexander D. Johnson.
PMID- 25114231
TI - Single-shot stand-off chemical identification of powders using random Raman
lasing.
AB - The task of identifying explosives, hazardous chemicals, and biological materials
from a safe distance is the subject we consider. Much of the prior work on stand
off spectroscopy using light has been devoted to generating a backward
propagating beam of light that can be used drive further spectroscopic processes.
The discovery of random lasing and, more recently, random Raman lasing provide a
mechanism for remotely generating copious amounts of chemically specific Raman
scattered light. The bright nature of random Raman lasing renders directionality
unnecessary, allowing for the detection and identification of chemicals from
large distances in real time. In this article, the single-shot remote
identification of chemicals at kilometer-scale distances is experimentally
demonstrated using random Raman lasing.
PMID- 25114230
TI - Interleukin-1 deficiency prolongs ovarian lifespan in mice.
AB - Oocyte endowment dwindles away during prepubertal and adult life until menopause
occurs, and apoptosis has been identified as a central mechanism responsible for
oocyte elimination. A few recent reports suggest that uncontrolled inflammation
may adversely affect ovarian reserve. We tested the possible role of the
proinflammatory cytokine IL-1 in the age-related exhaustion of ovarian reserve
using IL-1alpha and IL-1beta-KO mice. IL-1alpha-KO mice showed a substantially
higher pregnancy rate and litter size compared with WT mice at advanced age. The
number of secondary and antral follicles was significantly higher in 2.5-mo-old
IL-1alpha-KO ovaries compared with WT ovaries. Serum anti-Mullerian hormone, a
putative marker of ovarian reserve, was markedly higher in IL-1alpha-KO mice from
2.5 mo onward, along with a greater ovarian response to gonadotropins. IL-1beta
KO mice displayed a comparable but more subtle prolongation of ovarian lifespan
compared with IL-1alpha-KO mice. The protein and mRNA of both IL-1alpha and IL
1beta mice were localized within the developing follicles (oocytes and granulosa
cells), and their ovarian mRNA levels increased with age. Molecular analysis
revealed decreased apoptotic signaling [higher B-cell lymphoma 2 (BCL-2) and
lower BCL-2-associated X protein levels], along with a marked attenuation in the
expression of genes coding for the proinflammatory cytokines IL-1beta, IL-6, and
TNF-alpha in ovaries of IL-1alpha-KO mice compared with WT mice. Taken together,
IL-1 emerges as an important participant in the age-related exhaustion of ovarian
reserve in mice, possibly by enhancing the expression of inflammatory genes and
promoting apoptotic pathways.
PMID- 25114232
TI - EFA6 controls Arf1 and Arf6 activation through a negative feedback loop.
AB - Guanine nucleotide exchange factors (GEFs) of the exchange factor for Arf6
(EFA6), brefeldin A-resistant Arf guanine nucleotide exchange factor (BRAG), and
cytohesin subfamilies activate small GTPases of the Arf family in endocytic
events. These ArfGEFs carry a pleckstrin homology (PH) domain in tandem with
their catalytic Sec7 domain, which is autoinhibitory and supports a positive
feedback loop in cytohesins but not in BRAGs, and has an as-yet unknown role in
EFA6 regulation. In this study, we analyzed how EFA6A is regulated by its PH and
C terminus (Ct) domains by reconstituting its GDP/GTP exchange activity on
membranes. We found that EFA6 has a previously unappreciated high efficiency
toward Arf1 on membranes and that, similar to BRAGs, its PH domain is not
autoinhibitory and strongly potentiates nucleotide exchange on anionic liposomes.
However, in striking contrast to both cytohesins and BRAGs, EFA6 is regulated by
a negative feedback loop, which is mediated by an allosteric interaction of Arf6
GTP with the PH-Ct domain of EFA6 and monitors the activation of Arf1 and Arf6
differentially. These observations reveal that EFA6, BRAG, and cytohesins have
unanticipated commonalities associated with divergent regulatory regimes. An
important implication is that EFA6 and cytohesins may combine in a mixed negative
positive feedback loop. By allowing EFA6 to sustain a pool of dormant Arf6-GTP,
such a circuit would fulfill the absolute requirement of cytohesins for
activation by Arf-GTP before amplification of their GEF activity by their
positive feedback loop.
PMID- 25114233
TI - Microbial-induced meprin beta cleavage in MUC2 mucin and a functional CFTR
channel are required to release anchored small intestinal mucus.
AB - The mucus that covers and protects the epithelium of the intestine is built
around its major structural component, the gel-forming MUC2 mucin. The gel
forming mucins have traditionally been assumed to be secreted as nonattached. The
colon has a two-layered mucus system where the inner mucus is attached to the
epithelium, whereas the small intestine normally has a nonattached mucus.
However, the mucus of the small intestine of meprin beta-deficient mice was now
found to be attached. Meprin beta is an endogenous zinc-dependent metalloprotease
now shown to cleave the N-terminal region of the MUC2 mucin at two specific
sites. When recombinant meprin beta was added to the attached mucus of meprin
beta-deficient mice, the mucus was detached from the epithelium. Similar to
meprin beta-deficient mice, germ-free mice have attached mucus as they did not
shed the membrane-anchored meprin beta into the luminal mucus. The ileal mucus of
cystic fibrosis (CF) mice with a nonfunctional cystic fibrosis transmembrane
conductance regulator (CFTR) channel was recently shown to be attached to the
epithelium. Addition of recombinant meprin beta to CF mucus did not release the
mucus, but further addition of bicarbonate rendered the CF mucus normal,
suggesting that MUC2 unfolding exposed the meprin beta cleavage sites. Mucus is
thus secreted attached to the goblet cells and requires an enzyme, meprin beta in
the small intestine, to be detached and released into the intestinal lumen. This
process regulates mucus properties, can be triggered by bacterial contact, and is
nonfunctional in CF due to poor mucin unfolding.
PMID- 25114234
TI - Bioengineered functional brain-like cortical tissue.
AB - The brain remains one of the most important but least understood tissues in our
body, in part because of its complexity as well as the limitations associated
with in vivo studies. Although simpler tissues have yielded to the emerging tools
for in vitro 3D tissue cultures, functional brain-like tissues have not. We
report the construction of complex functional 3D brain-like cortical tissue,
maintained for months in vitro, formed from primary cortical neurons in modular
3D compartmentalized architectures with electrophysiological function. We show
that, on injury, this brain-like tissue responds in vitro with biochemical and
electrophysiological outcomes that mimic observations in vivo. This modular 3D
brain-like tissue is capable of real-time nondestructive assessments, offering
previously unidentified directions for studies of brain homeostasis and injury.
PMID- 25114237
TI - Fair sampling perspective on an apparent violation of duality.
AB - In the event in which a quantum mechanical particle can pass from an initial
state to a final state along two possible paths, the duality principle states
that "the simultaneous observation of wave and particle behavior is prohibited"
[Scully MO, Englert B-G, Walther H (1991) Nature 351:111-116]. Whereas wave
behavior is associated with the observation of interference fringes, particle
behavior generally corresponds to the acquisition of which-path information by
means of coupling the paths to a measuring device or part of their environment.
In this paper, we show how the consequences of duality change when allowing for
biased sampling, that is, postselected measurements on specific degrees of
freedom of the environment of the two-path state. Our work gives insight into a
possible mechanism for obtaining simultaneous high which-path information and
high-visibility fringes in a single experiment. Further, our results introduce
previously unidentified avenues for experimental tests of duality.
PMID- 25114236
TI - Marine ammonia-oxidizing archaeal isolates display obligate mixotrophy and wide
ecotypic variation.
AB - Ammonia-oxidizing archaea (AOA) are now implicated in exerting significant
control over the form and availability of reactive nitrogen species in marine
environments. Detailed studies of specific metabolic traits and physicochemical
factors controlling their activities and distribution have not been well
constrained in part due to the scarcity of isolated AOA strains. Here, we report
the isolation of two new coastal marine AOA, strains PS0 and HCA1. Comparison of
the new strains to Nitrosopumilus maritimus strain SCM1, the only marine AOA in
pure culture thus far, demonstrated distinct adaptations to pH, salinity, organic
carbon, temperature, and light. Strain PS0 sustained nearly 80% of ammonia
oxidation activity at a pH as low as 5.9, indicating that coastal strains may be
less sensitive to the ongoing reduction in ocean pH. Notably, the two novel
isolates are obligate mixotrophs that rely on uptake and assimilation of organic
carbon compounds, suggesting a direct coupling between chemolithotrophy and
organic matter assimilation in marine food webs. All three isolates showed only
minor photoinhibition at 15 uE ? m(-2) ? s(-1) and rapid recovery of ammonia
oxidation in the dark, consistent with an AOA contribution to the primary nitrite
maximum and the plausibility of a diurnal cycle of archaeal ammonia oxidation
activity in the euphotic zone. Together, these findings highlight an unexpected
adaptive capacity within closely related marine group I Archaea and provide new
understanding of the physiological basis of the remarkable ecological success
reflected by their generally high abundance in marine environments.
PMID- 25114235
TI - Small RNA combination therapy for lung cancer.
AB - MicroRNAs (miRNAs) and siRNAs have enormous potential as cancer therapeutics, but
their effective delivery to most solid tumors has been difficult. Here, we show
that a new lung-targeting nanoparticle is capable of delivering miRNA mimics and
siRNAs to lung adenocarcinoma cells in vitro and to tumors in a genetically
engineered mouse model of lung cancer based on activation of oncogenic Kirsten
rat sarcoma viral oncogene homolog (Kras) and loss of p53 function. Therapeutic
delivery of miR-34a, a p53-regulated tumor suppressor miRNA, restored miR-34a
levels in lung tumors, specifically down-regulated miR-34a target genes, and
slowed tumor growth. The delivery of siRNAs targeting Kras reduced Kras gene
expression and MAPK signaling, increased apoptosis, and inhibited tumor growth.
The combination of miR-34a and siRNA targeting Kras improved therapeutic
responses over those observed with either small RNA alone, leading to tumor
regression. Furthermore, nanoparticle-mediated small RNA delivery plus
conventional, cisplatin-based chemotherapy prolonged survival in this model
compared with chemotherapy alone. These findings demonstrate that RNA combination
therapy is possible in an autochthonous model of lung cancer and provide
preclinical support for the use of small RNA therapies in patients who have
cancer.
PMID- 25114238
TI - Collective credit allocation in science.
AB - Collaboration among researchers is an essential component of the modern
scientific enterprise, playing a particularly important role in multidisciplinary
research. However, we continue to wrestle with allocating credit to the coauthors
of publications with multiple authors, because the relative contribution of each
author is difficult to determine. At the same time, the scientific community runs
an informal field-dependent credit allocation process that assigns credit in a
collective fashion to each work. Here we develop a credit allocation algorithm
that captures the coauthors' contribution to a publication as perceived by the
scientific community, reproducing the informal collective credit allocation of
science. We validate the method by identifying the authors of Nobel-winning
papers that are credited for the discovery, independent of their positions in the
author list. The method can also compare the relative impact of researchers
working in the same field, even if they did not publish together. The ability to
accurately measure the relative credit of researchers could affect many aspects
of credit allocation in science, potentially impacting hiring, funding, and
promotion decisions.
PMID- 25114239
TI - Hybrid biosynthetic gene therapy vector development and dual engineering
capacity.
AB - Genetic vaccines offer a treatment opportunity based upon successful gene
delivery to specific immune cell modulators. Driving the process is the vector
chosen for gene cargo packaging and subsequent delivery to antigen-presenting
cells (APCs) capable of triggering an immune cascade. As such, the delivery
process must successfully navigate a series of requirements and obstacles
associated with the chosen vector and target cell. In this work, we present the
development and assessment of a hybrid gene delivery vector containing biological
and biomaterial components. Each component was chosen to design and engineer gene
delivery separately in a complimentary and fundamentally distinct fashion. A
bacterial (Escherichia coli) inner core and a biomaterial [poly(beta-amino
ester)]-coated outer surface allowed the simultaneous application of molecular
biology and polymer chemistry to address barriers associated with APC gene
delivery, which include cellular uptake and internalization, phagosomal escape,
and intracellular cargo concentration. The approach combined and synergized
normally disparate vector properties and tools, resulting in increased in vitro
gene delivery beyond individual vector components or commercially available
transfection agents. Furthermore, the hybrid device demonstrated a strong,
efficient, and safe in vivo humoral immune response compared with traditional
forms of antigen delivery. In summary, the flexibility, diversity, and potential
of the hybrid design were developed and featured in this work as a platform for
multivariate engineering at the vector and cellular scales for new applications
in gene delivery immunotherapy.
PMID- 25114240
TI - A new tubulin-binding site and pharmacophore for microtubule-destabilizing
anticancer drugs.
AB - The recent success of antibody-drug conjugates (ADCs) in the treatment of cancer
has led to a revived interest in microtubule-destabilizing agents. Here, we
determined the high-resolution crystal structure of the complex between tubulin
and maytansine, which is part of an ADC that is approved by the US Food and Drug
Administration (FDA) for the treatment of advanced breast cancer. We found that
the drug binds to a site on beta-tubulin that is distinct from the vinca domain
and that blocks the formation of longitudinal tubulin interactions in
microtubules. We also solved crystal structures of tubulin in complex with both a
variant of rhizoxin and the phase 1 drug PM060184. Consistent with biochemical
and mutagenesis data, we found that the two compounds bound to the same site as
maytansine and that the structures revealed a common pharmacophore for the three
ligands. Our results delineate a distinct molecular mechanism of action for the
inhibition of microtubule assembly by clinically relevant agents. They further
provide a structural basis for the rational design of potent microtubule
destabilizing agents, thus opening opportunities for the development of next
generation ADCs for the treatment of cancer.
PMID- 25114241
TI - Nucleoprotein architectures regulating the directionality of viral integration
and excision.
AB - The virally encoded site-specific recombinase Int collaborates with its accessory
DNA bending proteins IHF, Xis, and Fis to assemble two distinct, very large,
nucleoprotein complexes that carry out either integrative or excisive
recombination along regulated and essentially unidirectional pathways. The core
of each complex consists of a tetramer of Integrase protein (Int), which is a
heterobivalent DNA binding protein that binds and bridges a core-type DNA site
(where strand cleavage and ligation are executed), and a distal arm-type site,
that is brought within range by one or more DNA bending proteins. The recent
determination of the patterns of these Int bridges has made it possible to think
realistically about the global architecture of the recombinogenic complexes.
Here, we combined the previously determined Int bridging patterns with in-gel
FRET experiments and in silico modeling to characterize and differentiate the two
400-kDa multiprotein Holiday junction recombination intermediates formed during
lambda integration and excision. The results lead to architectural models that
explain how integration and excision are regulated in lambda site-specific
recombination. Our confidence in the basic features of these architectures is
based on the redundancy and self-consistency of the underlying data from two very
different experimental approaches to establish bridging interactions, a set of
strategic intracomplex distances from FRET experiments, and the model's ability
to explain key aspects of the integrative and excisive recombination pathways,
such as topological changes, the mechanism of capturing attB, and the features of
asymmetry and flexibility within the complexes.
PMID- 25114242
TI - Coevolutionary information, protein folding landscapes, and the thermodynamics of
natural selection.
AB - The energy landscape used by nature over evolutionary timescales to select
protein sequences is essentially the same as the one that folds these sequences
into functioning proteins, sometimes in microseconds. We show that genomic data,
physical coarse-grained free energy functions, and family-specific information
theoretic models can be combined to give consistent estimates of energy landscape
characteristics of natural proteins. One such characteristic is the effective
temperature T(sel) at which these foldable sequences have been selected in
sequence space by evolution. T(sel) quantifies the importance of folded-state
energetics and structural specificity for molecular evolution. Across all protein
families studied, our estimates for T(sel) are well below the experimental
folding temperatures, indicating that the energy landscapes of natural foldable
proteins are strongly funneled toward the native state.
PMID- 25114244
TI - Dopamine challenge reveals neuroadaptive changes in marijuana abusers.
PMID- 25114245
TI - Quasi-resonant circulation regimes and hemispheric synchronization of extreme
weather in boreal summer.
AB - The recent decade has seen an exceptional number of high-impact summer extremes
in the Northern Hemisphere midlatitudes. Many of these events were associated
with anomalous jet stream circulation patterns characterized by persistent high
amplitude quasi-stationary Rossby waves. Two mechanisms have recently been
proposed that could provoke such patterns: (i) a weakening of the zonal mean jets
and (ii) an amplification of quasi-stationary waves by resonance between free and
forced waves in midlatitude waveguides. Based upon spectral analysis of the
midtroposphere wind field, we show that the persistent jet stream patterns were,
in the first place, due to an amplification of quasi-stationary waves with zonal
wave numbers 6-8. However, we also detect a weakening of the zonal mean jet
during these events; thus both mechanisms appear to be important. Furthermore, we
demonstrate that the anomalous circulation regimes lead to persistent surface
weather conditions and therefore to midlatitude synchronization of extreme heat
and rainfall events on monthly timescales. The recent cluster of resonance events
has resulted in a statistically significant increase in the frequency of high
amplitude quasi-stationary waves of wave numbers 7 and 8 in July and August. We
show that this is a robust finding that holds for different pressure levels and
reanalysis products. We argue that recent rapid warming in the Arctic and
associated changes in the zonal mean zonal wind have created favorable conditions
for double jet formation in the extratropics, which promotes the development of
resonant flow regimes.
PMID- 25114243
TI - Structural basis for the recruitment and activation of the Legionella
phospholipase VipD by the host GTPase Rab5.
AB - A challenge for microbial pathogens is to assure that their translocated effector
proteins target only the correct host cell compartment during infection. The
Legionella pneumophila effector vacuolar protein sorting inhibitor protein D
(VipD) localizes to early endosomal membranes and alters their lipid and protein
composition, thereby protecting the pathogen from endosomal fusion. This process
requires the phospholipase A1 (PLA1) activity of VipD that is triggered
specifically on VipD binding to the host cell GTPase Rab5, a key regulator of
endosomes. Here, we present the crystal structure of VipD in complex with
constitutively active Rab5 and reveal the molecular mechanism underlying PLA1
activation. An active site-obstructing loop that originates from the C-terminal
domain of VipD is repositioned on Rab5 binding, thereby exposing the catalytic
pocket within the N-terminal PLA1 domain. Substitution of amino acid residues
located within the VipD-Rab5 interface prevented Rab5 binding and PLA1 activation
and caused a failure of VipD mutant proteins to target to Rab5-enriched endosomal
structures within cells. Experimental and computational analyses confirmed an
extended VipD-binding interface on Rab5, explaining why this L. pneumophila
effector can compete with cellular ligands for Rab5 binding. Together, our data
explain how the catalytic activity of a microbial effector can be precisely
linked to its subcellular localization.
PMID- 25114246
TI - A cellular solution to an information-processing problem.
AB - Signaling receptors on the cell surface are mobile and have evolved to
efficiently sense and process mechanical or chemical information. We pose the
problem of identifying the optimal strategy for placing a collection of
distributed and mobile sensors to faithfully estimate a signal that varies in
space and time. The optimal strategy has to balance two opposing objectives: the
need to locally assemble sensors to reduce estimation noise and the need to
spread them to reduce spatial error. This results in a phase transition in the
space of strategies as a function of sensor density and efficiency. We show that
these optimal strategies have been arrived at multiple times in diverse cell
biology contexts, including the stationary lattice architecture of receptors on
the bacterial cell surface and the active clustering of cell-surface signaling
receptors in metazoan cells.
PMID- 25114247
TI - Mapping the lambda Integrase bridges in the nucleoprotein Holliday junction
intermediates of viral integrative and excisive recombination.
AB - The site-specific recombinase encoded by bacteriophage lambda [lambda Integrase
(Int)] is responsible for integrating and excising the viral chromosome into and
out of the chromosome of its Escherichia coli host. In contrast to the other well
studied and highly exploited tyrosine recombinase family members, such as Cre and
Flp, Int carries out a reaction that is highly directional, tightly regulated,
and depends on an ensemble of accessory DNA bending proteins acting on 240 bp of
DNA encoding 16 protein binding sites. This additional complexity enables two
pathways, integrative and excisive recombination, whose opposite, and effectively
irreversible, directions are dictated by different physiological and
environmental signals. Int recombinase is a heterobivalent DNA binding protein
that binds via its small amino-terminal domain to high affinity arm-type DNA
sites and via its large, compound carboxyl-terminal domain to core-type DNA
sites, where DNA cleavage and ligation are executed. Each of the four Int
protomers, within a multiprotein 400-kDa recombinogenic complex, is thought to
bind and, with the aid of DNA bending proteins, bridge one arm- and one core-type
DNA site. Despite a wealth of genetic, biochemical, and functional information
generated by many laboratories over the last 50 y, it has not been possible to
decipher the patterns of Int bridges, an essential step in understanding the
architectures responsible for regulated directionality of recombination. We used
site-directed chemical cross-linking of Int in trapped Holliday junction
recombination intermediates and recombination reactions with chimeric
recombinases, to identify the unique and monogamous patterns of Int bridges for
integrative and excisive recombination.
PMID- 25114249
TI - Electron spin changes during general anesthesia in Drosophila.
AB - We show that the general anesthetics xenon, sulfur hexafluoride, nitrous oxide,
and chloroform cause rapid increases of different magnitude and time course in
the electron spin content of Drosophila. With the exception of CHCl3, these
changes are reversible. Anesthetic-resistant mutant strains of Drosophila exhibit
a different pattern of spin responses to anesthetic. In two such mutants, the
spin response to CHCl3 is absent. We propose that these spin changes are caused
by perturbation of the electronic structure of proteins by general anesthetics.
Using density functional theory, we show that general anesthetics perturb and
extend the highest occupied molecular orbital of a nine-residue alpha-helix. The
calculated perturbations are qualitatively in accord with the Meyer-Overton
relationship and some of its exceptions. We conclude that there may be a
connection between spin, electron currents in cells, and the functioning of the
nervous system.
PMID- 25114248
TI - Distinct isoform of FABP7 revealed by screening for retroelement-activated genes
in diffuse large B-cell lymphoma.
AB - Remnants of ancient transposable elements (TEs) are abundant in mammalian
genomes. These sequences harbor multiple regulatory motifs and hence are capable
of influencing expression of host genes. In response to environmental changes,
TEs are known to be released from epigenetic repression and to become
transcriptionally active. Such activation could also lead to lineage
inappropriate activation of oncogenes, as one study described in Hodgkin
lymphoma. However, little further evidence for this mechanism in other cancers
has been reported. Here, we reanalyzed whole transcriptome data from a large
cohort of patients with diffuse large B-cell lymphoma (DLBCL) compared with
normal B-cell centroblasts to detect genes ectopically expressed through
activation of TE promoters. We have identified 98 such TE-gene chimeric
transcripts that were exclusively expressed in primary DLBCL cases and confirmed
several in DLBCL-derived cell lines. We further characterized a TE-gene chimeric
transcript involving a fatty acid-binding protein gene (LTR2-FABP7), normally
expressed in brain, that was ectopically expressed in a subset of DLBCL patients
through the use of an endogenous retroviral LTR promoter of the LTR2 family. The
LTR2-FABP7 chimeric transcript encodes a novel chimeric isoform of the protein
with characteristics distinct from native FABP7. In vitro studies reveal a
dependency for DLBCL cell line proliferation and growth on LTR2-FABP7 chimeric
protein expression. Taken together, these data demonstrate the significance of
TEs as regulators of aberrant gene expression in cancer and suggest that LTR2
FABP7 may contribute to the pathogenesis of DLBCL in a subgroup of patients.
PMID- 25114250
TI - Chaperone-enhanced purification of unconventional myosin 15, a molecular motor
specialized for stereocilia protein trafficking.
AB - Unconventional myosin 15 is a molecular motor expressed in inner ear hair cells
that transports protein cargos within developing mechanosensory stereocilia.
Mutations of myosin 15 cause profound hearing loss in humans and mice; however,
the properties of this motor and its regulation within the stereocilia organelle
are unknown. To address these questions, we expressed a subfragment 1-like (S1)
truncation of mouse myosin 15, comprising the predicted motor domain plus three
light-chain binding sites. Following unsuccessful attempts to express functional
myosin 15-S1 using the Spodoptera frugiperda (Sf9)-baculovirus system, we
discovered that coexpression of the muscle-myosin-specific chaperone UNC45B, in
addition to the chaperone heat-shock protein 90 (HSP90) significantly increased
the yield of functional protein. Surprisingly, myosin 15-S1 did not bind
calmodulin with high affinity. Instead, the IQ domains bound essential and
regulatory light chains that are normally associated with class II myosins. We
show that myosin 15-S1 is a barbed-end-directed motor that moves actin filaments
in a gliding assay (~ 430 nm . s(-1) at 30 degrees C), using a power stroke of
7.9 nm. The maximum ATPase rate (k(cat) ~ 6 s(-1)) was similar to the actin
detachment rate (k(det) = 6.2 s(-1)) determined in single molecule optical
trapping experiments, indicating that myosin 15-S1 was rate limited by transit
through strongly actin-bound states, similar to other processive myosin motors.
Our data further indicate that in addition to folding muscle myosin, UNC45B
facilitates maturation of an unconventional myosin. We speculate that chaperone
coexpression may be a simple method to optimize the purification of other myosin
motors from Sf9 insect cells.
PMID- 25114251
TI - DELAY OF GERMINATION 1 mediates a conserved coat-dormancy mechanism for the
temperature- and gibberellin-dependent control of seed germination.
AB - Seed germination is an important life-cycle transition because it determines
subsequent plant survival and reproductive success. To detect optimal
spatiotemporal conditions for germination, seeds act as sophisticated
environmental sensors integrating information such as ambient temperature. Here
we show that the delay of germination 1 (DOG1) gene, known for providing dormancy
adaptation to distinct environments, determines the optimal temperature for seed
germination. By reciprocal gene-swapping experiments between Brassicaceae species
we show that the DOG1-mediated dormancy mechanism is conserved. Biomechanical
analyses show that this mechanism regulates the material properties of the
endosperm, a seed tissue layer acting as germination barrier to control coat
dormancy. We found that DOG1 inhibits the expression of gibberellin (GA)
regulated genes encoding cell-wall remodeling proteins in a temperature-dependent
manner. Furthermore we demonstrate that DOG1 causes temperature-dependent
alterations in the seed GA metabolism. These alterations in hormone metabolism
are brought about by the temperature-dependent differential expression of genes
encoding key enzymes of the GA biosynthetic pathway. These effects of DOG1 lead
to a temperature-dependent control of endosperm weakening and determine the
optimal temperature for germination. The conserved DOG1-mediated coat-dormancy
mechanism provides a highly adaptable temperature-sensing mechanism to control
the timing of germination.
PMID- 25114253
TI - The Holocene temperature conundrum.
AB - A recent temperature reconstruction of global annual temperature shows Early
Holocene warmth followed by a cooling trend through the Middle to Late Holocene
[Marcott SA, et al., 2013, Science 339(6124):1198-1201]. This global cooling is
puzzling because it is opposite from the expected and simulated global warming
trend due to the retreating ice sheets and rising atmospheric greenhouse gases.
Our critical reexamination of this contradiction between the reconstructed
cooling and the simulated warming points to potentially significant biases in
both the seasonality of the proxy reconstruction and the climate sensitivity of
current climate models.
PMID- 25114254
TI - Global agriculture and carbon trade-offs.
AB - Feeding a growing and increasingly affluent world will require expanded
agricultural production, which may require converting grasslands and forests into
cropland. Such conversions can reduce carbon storage, habitat provision, and
other ecosystem services, presenting difficult societal trade-offs. In this
paper, we use spatially explicit data on agricultural productivity and carbon
storage in a global analysis to find where agricultural extensification should
occur to meet growing demand while minimizing carbon emissions from land use
change. Selective extensification saves ~ 6 billion metric tons of carbon
compared with a business-as-usual approach, with a value of approximately $1
trillion (2012 US dollars) using recent estimates of the social cost of carbon.
This type of spatially explicit geospatial analysis can be expanded to include
other ecosystem services and other industries to analyze how to minimize
conflicts between economic development and environmental sustainability.
PMID- 25114252
TI - Native microbiome impedes vertical transmission of Wolbachia in Anopheles
mosquitoes.
AB - Over evolutionary time, Wolbachia has been repeatedly transferred between host
species contributing to the widespread distribution of the symbiont in
arthropods. For novel infections to be maintained, Wolbachia must infect the
female germ line after being acquired by horizontal transfer. Although
mechanistic examples of horizontal transfer exist, there is a poor understanding
of factors that lead to successful vertical maintenance of the acquired
infection. Using Anopheles mosquitoes (which are naturally uninfected by
Wolbachia) we demonstrate that the native mosquito microbiota is a major barrier
to vertical transmission of a horizontally acquired Wolbachia infection. After
injection into adult Anopheles gambiae, some strains of Wolbachia invade the germ
line, but are poorly transmitted to the next generation. In Anopheles stephensi,
Wolbachia infection elicited massive blood meal-induced mortality, preventing
development of progeny. Manipulation of the mosquito microbiota by antibiotic
treatment resulted in perfect maternal transmission at significantly elevated
titers of the wAlbB Wolbachia strain in A. gambiae, and alleviated blood meal
induced mortality in A. stephensi enabling production of Wolbachia-infected
offspring. Microbiome analysis using high-throughput sequencing identified that
the bacterium Asaia was significantly reduced by antibiotic treatment in both
mosquito species. Supplementation of an antibiotic-resistant mutant of Asaia to
antibiotic-treated mosquitoes completely inhibited Wolbachia transmission and
partly contributed to blood meal-induced mortality. These data suggest that the
components of the native mosquito microbiota can impede Wolbachia transmission in
Anopheles. Incompatibility between the microbiota and Wolbachia may in part
explain why some hosts are uninfected by this endosymbiont in nature.
PMID- 25114255
TI - Fractal branching organizations of Ediacaran rangeomorph fronds reveal a lost
Proterozoic body plan.
AB - The branching morphology of Ediacaran rangeomorph fronds has no exact counterpart
in other complex macroorganisms. As such, these fossils pose major questions as
to growth patterns, functional morphology, modes of feeding, and adaptive
optimality. Here, using parametric Lindenmayer systems, a formal model of
rangeomorph morphologies reveals a fractal body plan characterized by self
similar, axial, apical, alternate branching. Consequent morphological
reconstruction for 11 taxa demonstrates an adaptive radiation based on 3D space
filling strategies. The fractal body plan of rangeomorphs is shown to maximize
surface area, consistent with diffusive nutrient uptake from the water column
(osmotrophy). The enigmas of rangeomorph morphology, evolution, and extinction
are resolved by the realization that they were adaptively optimized for unique
ecological and geochemical conditions in the late Proterozoic. Changes in ocean
conditions associated with the Cambrian explosion sealed their fate.
PMID- 25114258
TI - Retraction for Schlaberg et al., XMRV is present in malignant prostatic
epithelium and is associated with prostate cancer, especially high-grade tumors.
PMID- 25114256
TI - The human dynamic clamp as a paradigm for social interaction.
AB - Social neuroscience has called for new experimental paradigms aimed toward real
time interactions. A distinctive feature of interactions is mutual information
exchange: One member of a pair changes in response to the other while
simultaneously producing actions that alter the other. Combining mathematical and
neurophysiological methods, we introduce a paradigm called the human dynamic
clamp (HDC), to directly manipulate the interaction or coupling between a human
and a surrogate constructed to behave like a human. Inspired by the dynamic clamp
used so productively in cellular neuroscience, the HDC allows a person to
interact in real time with a virtual partner itself driven by well-established
models of coordination dynamics. People coordinate hand movements with the
visually observed movements of a virtual hand, the parameters of which depend on
input from the subject's own movements. We demonstrate that HDC can be extended
to cover a broad repertoire of human behavior, including rhythmic and discrete
movements, adaptation to changes of pacing, and behavioral skill learning as
specified by a virtual "teacher." We propose HDC as a general paradigm, best
implemented when empirically verified theoretical or mathematical models have
been developed in a particular scientific field. The HDC paradigm is powerful
because it provides an opportunity to explore parameter ranges and perturbations
that are not easily accessible in ordinary human interactions. The HDC not only
enables to test the veracity of theoretical models, it also illuminates features
that are not always apparent in real-time human social interactions and the brain
correlates thereof.
PMID- 25114257
TI - Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to
human transmission of MERS coronavirus.
AB - Middle East respiratory syndrome coronavirus (MERS-CoV) currently spreads in
humans and causes ~ 36% fatality in infected patients. Believed to have
originated from bats, MERS-CoV is genetically related to bat coronaviruses HKU4
and HKU5. To understand how bat coronaviruses transmit to humans, we investigated
the receptor usage and cell entry activity of the virus-surface spike proteins of
HKU4 and HKU5. We found that dipeptidyl peptidase 4 (DPP4), the receptor for MERS
CoV, is also the receptor for HKU4, but not HKU5. Despite sharing a common
receptor, MERS-CoV and HKU4 spikes demonstrated functional differences. First,
whereas MERS-CoV prefers human DPP4 over bat DPP4 as its receptor, HKU4 shows the
opposite trend. Second, in the absence of exogenous proteases, both MERS-CoV and
HKU4 spikes mediate pseudovirus entry into bat cells, whereas only MERS-CoV
spike, but not HKU4 spike, mediates pseudovirus entry into human cells. Thus,
MERS-CoV, but not HKU4, has adapted to use human DPP4 and human cellular
proteases for efficient human cell entry, contributing to the enhanced
pathogenesis of MERS-CoV in humans. These results establish DPP4 as a functional
receptor for HKU4 and host cellular proteases as a host range determinant for
HKU4. They also suggest that DPP4-recognizing bat coronaviruses threaten human
health because of their spikes' capability to adapt to human cells for cross
species transmissions.
PMID- 25114259
TI - Tip-link protein protocadherin 15 interacts with transmembrane channel-like
proteins TMC1 and TMC2.
AB - The tip link protein protocadherin 15 (PCDH15) is a central component of the
mechanotransduction complex in auditory and vestibular hair cells. PCDH15 is
hypothesized to relay external forces to the mechanically gated channel located
near its cytoplasmic C terminus. How PCDH15 is coupled to the transduction
machinery is not clear. Using a membrane-based two-hybrid screen to identify
proteins that bind to PCDH15, we detected an interaction between zebrafish
Pcdh15a and an N-terminal fragment of transmembrane channel-like 2a (Tmc2a).
Tmc2a is an ortholog of mammalian TMC2, which along with TMC1 has been implicated
in mechanotransduction in mammalian hair cells. Using the above-mentioned two
hybrid assay, we found that zebrafish Tmc1 and Tmc2a can interact with the CD1 or
CD3 cytoplasmic domain isoforms of Pcdh15a, and this interaction depends on the
common region shared between the two Pcdh15 isoforms. Moreover, an interaction
between mouse PCDH15-CD3 and TMC1 or TMC2 was observed in both yeast two-hybrid
assays and coimmunoprecipitation experiments. To determine whether the Pcdh15-Tmc
interaction is relevant to mechanotransduction in vivo, we overexpressed N
terminal fragments of Tmc2a in zebrafish hair cells. Overexpression of the Tmc2a
N terminus results in mislocalization of Pcdh15a within hair bundles, together
with a significant decrease in mechanosensitive responses, suggesting that a
Pcdh15a-Tmc complex is critical for mechanotransduction. Together, these results
identify an evolutionarily conserved association between the fish and mouse
orthologs of PCDH15 and TMC1 and TMC2, supporting the notion that TMCs are key
components of the transduction complex in hair cells.
PMID- 25114261
TI - Patterned progression of bacterial populations in the premature infant gut.
AB - In the weeks after birth, the gut acquires a nascent microbiome, and starts its
transition to bacterial population equilibrium. This early-in-life microbial
population quite likely influences later-in-life host biology. However, we know
little about the governance of community development: does the gut serve as a
passive incubator where the first organisms randomly encountered gain entry and
predominate, or is there an orderly progression of members joining the community
of bacteria? We used fine interval enumeration of microbes in stools from
multiple subjects to answer this question. We demonstrate via 16S rRNA gene
pyrosequencing of 922 specimens from 58 subjects that the gut microbiota of
premature infants residing in a tightly controlled microbial environment
progresses through a choreographed succession of bacterial classes from Bacilli
to Gammaproteobacteria to Clostridia, interrupted by abrupt population changes.
As infants approach 33-36 wk postconceptional age (corresponding to the third to
the twelfth weeks of life depending on gestational age at birth), the gut is well
colonized by anaerobes. Antibiotics, vaginal vs. Caesarian birth, diet, and age
of the infants when sampled influence the pace, but not the sequence, of
progression. Our results suggest that in infants in a microbiologically
constrained ecosphere of a neonatal intensive care unit, gut bacterial
communities have an overall nonrandom assembly that is punctuated by microbial
population abruptions. The possibility that the pace of this assembly depends
more on host biology (chiefly gestational age at birth) than identifiable
exogenous factors warrants further consideration.
PMID- 25114263
TI - Targeted correction of RUNX1 mutation in FPD patient-specific induced pluripotent
stem cells rescues megakaryopoietic defects.
AB - Familial platelet disorder with predisposition to acute myeloid leukemia
(FPD/AML) is an autosomal dominant disease of the hematopoietic system that is
caused by heterozygous mutations in RUNX1. FPD/AML patients have a bleeding
disorder characterized by thrombocytopenia with reduced platelet numbers and
functions, and a tendency to develop AML. No suitable animal models exist for
FPD/AML, as Runx11/2 mice and zebra fish do not develop bleeding disorders or
leukemia. Here we derived induced pluripotent stem cells (iPSCs) from 2 patients
in a family with FPD/AML, and found that the FPD iPSCs display defects in
megakaryocytic differentiation in vitro. We corrected the RUNX1 mutation in 1 FPD
iPSC line through gene targeting, which led to normalization of megakaryopoiesis
of the iPSCs in culture. Our results demonstrate successful in vitro modeling of
FPD with patient-specific iPSCs and confirm that RUNX1 mutations are responsible
for megakaryopoietic defects in FPD patients.
PMID- 25114262
TI - Expression profiling associates blood and brain glucocorticoid receptor signaling
with trauma-related individual differences in both sexes.
AB - Delineating the molecular basis of individual differences in the stress response
is critical to understanding the pathophysiology and treatment of posttraumatic
stress disorder (PTSD). In this study, 7 d after predator-scent-stress (PSS)
exposure, male and female rats were classified into vulnerable (i.e., "PTSD
like") and resilient (i.e., minimally affected) phenotypes on the basis of their
performance on a variety of behavioral measures. Genome-wide expression profiling
in blood and two limbic brain regions (amygdala and hippocampus), followed by
quantitative PCR validation, was performed in these two groups of animals, as
well as in an unexposed control group. Differentially expressed genes were
identified in blood and brain associated with PSS-exposure and with distinct
behavioral profiles postexposure. There was a small but significant between
tissue overlap (4-21%) for the genes associated with exposure-related individual
differences, indicating convergent gene expression in both sexes. To uncover
convergent signaling pathways across tissue and sex, upstream
activated/deactivated transcription factors were first predicted for each tissue
and then the respective pathways were identified. Glucocorticoid receptor (GR)
signaling was the only convergent pathway associated with individual differences
when using the most stringent statistical threshold. Corticosterone treatment 1 h
after PSS-exposure prevented anxiety and hyperarousal 7 d later in both sexes,
confirming the GR involvement in the PSS behavioral response. In conclusion,
genes and pathways associated with extreme differences in the traumatic stress
behavioral response can be distinguished from those associated with trauma
exposure. Blood-based biomarkers can predict aspects of brain signaling. GR
signaling is a convergent signaling pathway, associated with trauma-related
individual differences in both sexes.
PMID- 25114264
TI - Human blood BDCA-1 dendritic cells differentiate into Langerhans-like cells with
thymic stromal lymphopoietin and TGF-beta.
AB - The ontogeny of human Langerhans cells (LCs) remains poorly characterized, in
particular the nature of LC precursors and the factors that may drive LC
differentiation. Here we report that thymic stromal lymphopoietin (TSLP), a
keratinocyte-derived cytokine involved in epithelial inflammation, cooperates
with transforming growth factor (TGF)-beta for the generation of LCs. We show
that primary human blood BDCA-1(+), but not BDCA-3(+), dendritic cells (DCs)
stimulated with TSLP and TGF-beta harbor a typical CD1a(+)Langerin(+) LC
phenotype. Electron microscopy established the presence of Birbeck granules, an
intracellular organelle specific to LCs. LC differentiation was not observed from
tonsil BDCA-1(+) and BDCA-3(+) subsets. TSLP + TGF-beta LCs had a mature
phenotype with high surface levels of CD80, CD86, and CD40. They induced a potent
CD4(+) T-helper (Th) cell expansion and differentiation into Th2 cells with
increased production of tumor necrosis factor-alpha and interleukin-6 compared
with CD34-derived LCs. Our findings establish a novel LC differentiation pathway
from BDCA-1(+) blood DCs with potential implications in epithelial inflammation.
Therapeutic targeting of TSLP may interfere with tissue LC repopulation from
circulating precursors.
PMID- 25114265
TI - "Pictures don't lie, seeing is believing": exploring attitudes to the
introduction of pictorial warnings on cigarette packs in Ghana.
AB - PURPOSE: To compare perceptions of text and pictorial warning labels on cigarette
packs among Ghanaian smokers and nonsmokers and to explore their views on the
introduction of pictorial warnings in Ghana. METHODS: Qualitative study involving
12 focus group discussions with 50 smokers and 35 nonsmokers aged 15 years and
older in Kumasi, Ghana. Semistructured discussion guides along with visual
discussant aids were used to explore the perception, acceptance, and potential
use of pictorial warning labels in Ghana. RESULTS: Health warnings combining text
and a picture were perceived by both smokers and nonsmokers to communicate health
messages more effectively than text-only or picture-only warnings. The effect of
text-only warnings was considered limited by low levels of literacy and by the
common practice of single stick sales rather than sales of packs. Of the 6 health
warnings tested, lung cancer, blindness, stroke, and throat/mouth cancer messages
were perceived to have the most impact on smoking behavior, including uptake and
quit attempts. CONCLUSIONS: Warning labels combining pictures and text have the
potential to reduce smoking uptake, increase quit attempts, and reduce smoking
appeal among smokers and nonsmokers in Ghana. Measures to prevent single stick
sales, or to promote health messages to purchasers of single sticks, are
required.
PMID- 25114266
TI - Necrotizing fasciitis of the hand and wrist due to Prevotella bivia.
PMID- 25114267
TI - An adjustable device to keep the thumb in opposition and prevent adduction
contracture after surgery or injury.
PMID- 25114268
TI - Read-back improves information transfer in simulated clinical crises.
AB - BACKGROUND: Safe and effective healthcare is frustrated by failures in
communication. Repeating back important information (read-back) is thought to
enhance the effectiveness of communication across many industries. However,
formal communication protocols are uncommon in healthcare teams. AIMS: We aimed
to quantify the effect of read-back on the transfer of information between
members of a healthcare team during a simulated clinical crisis. We hypothesised
that reading back information provided by other team members would result in
better knowledge of that information by the receiver than verbal response without
read-back or no verbal response. METHOD: Postanaesthesia care unit nurses and
anaesthetic assistants were given clinically relevant items of information at the
start of 88 simulations. A clinical crisis prompted calling an anaesthetist, with
no prior knowledge of the patient. Using video recordings of the simulations, we
noted each time a piece of information was mentioned to the anaesthetist. Their
response was coded as read-back, verbal response without read-back or no verbal
response. RESULTS: If the anaesthetists read back the item of information, or
otherwise verbally responded, they were, respectively, 8.27 (p<0.001) or 3.16
(p=0.03) times more likely to know the information compared with no verbal
response. CONCLUSIONS: Our results suggest that training healthcare teams to use
read-back techniques could increase information transfer between team members
with the potential for improved patient safety. More work is needed to confirm
these findings.
PMID- 25114269
TI - Biomarkers of susceptibility to chemical carcinogens: the example of non-Hodgkin
lymphomas.
AB - BACKGROUND: Genetic susceptibly to suspected chemical and environmental
carcinogens may modify the response to exposure. The aim of this review was to
explore the issues involved in the study of gene-environment interactions, and to
consider the use of susceptibility biomarkers in cancer epidemiology, using non
Hodgkin lymphoma (NHL) as an example. SOURCES OF DATA: PubMed, EMBASE and Web of
Science were searched for peer-reviewed articles considering biomarkers of
susceptibility to chemical, agricultural and industrial carcinogens in the
aetiology of NHL. AREAS OF AGREEMENT: The results suggest a modifying role for
genetic susceptibility to a number of occupational and environmental exposures
including organochlorines, chlorinated solvents, chlordanes and benzene in the
aetiology of NHL. The potential importance of these gene-environment interactions
in NHL may help to explain the lack of definitive carcinogens identified to date
for this malignancy. AREAS OF CONTROVERSY: Although a large number of genetic
variants and gene-environment interactions have been explored for NHL, to date
replication is lacking and therefore the findings remain to be validated. GROWING
POINTS AND AREAS TIMELY FOR DEVELOPING RESEARCH: These findings highlight the
need for novel standardized methodologies in the study of genetic susceptibility
to chemical carcinogens.
PMID- 25114270
TI - Police exposure to infectious agents: an audit of protective policies.
AB - BACKGROUND: As first responders, police officers may be exposed to infectious
agents such as hepatitis viruses and human immunodeficiency virus. Their risk of
infection by these viruses can be reduced with training, monitoring and, with
some viruses, vaccination. AIMS: To examine infection prevention policies and
practices among police departments and determine provision of vaccination and
infection prevention education programmes. METHODS: A questionnaire sent to all
police departments in five counties of south-eastern Pennsylvania to capture
information about department size, immunization policies and practices, record
keeping, infection prevention education and monitoring of exposures. RESULTS:
Ninety-six of 168 departments responded (57%). Among these, policies requiring
pre-employment physical examinations were almost universal (95%). Vaccination
policies were less common with <15% requiring and 50% recommending hepatitis,
tetanus or influenza vaccination for officers. Few departments took action to
provide (2%) or cover the cost (21%) of vaccination. Fewer than 12% maintained
vaccination records. Education about the risk of infectious agents was offered by
60% of the responding departments, but often just once at the start of
employment. Fewer than half of the departments had systems to collect exposure
information. CONCLUSIONS: Police departments have opportunities to improve
policies and practices for infection prevention and control. Accurate
documentation of vaccination status is essential to ensure provision of
appropriate post-exposure assessment and treatment. Better reporting of exposure
will improve understanding of the infection transmission risk, enhancing the
ability to offer targeted education and services to officers.
PMID- 25114271
TI - Re: Microsatellite instability and BRAF mutation testing in colorectal cancer
prognostication.
PMID- 25114272
TI - Response.
PMID- 25114273
TI - Clinical genomics: when whole genome sequencing is like a whole-body CT scan.
PMID- 25114274
TI - Improving the 510(k) FDA process for cardiac troponin assays: in search of common
ground.
PMID- 25114275
TI - EMA's proposal to vet drug research that uses its data is "outdated," say
critics.
PMID- 25114276
TI - Response.
PMID- 25114277
TI - Commentary on the 2014 BP guidelines from the panel appointed to the Eighth Joint
National Committee (JNC 8).
AB - The recently published article "2014 Evidence-based guideline for the management
of high blood pressure in adults: Report from the panel members appointed to the
Eighth Joint National Committee (JNC 8)" (James et al., JAMA 311: 507-520, 2014)
has generated considerable controversy. In this commentary, we evaluate the
document and compare the recommendations contained within it with those of the
JNC 7 and other national and international guidelines. The evidence quality
rating approach followed by the article "2014 Evidence-based guideline for the
management of high blood pressure in adults: Report from the panel members
appointed to the Eighth Joint National Committee (JNC 8)" (James et al., JAMA
311: 507-520, 2014) disqualified nearly 98% of previous studies from review; as a
result, some of the key recommendations were on the basis of expert opinion
alone. We are especially concerned that the recommendation to raise the
systolic/diastolic BP levels at which treatment is initiated to >=150/>=90 mmHg
in adults>=60 years old may affect cardiovascular and renal health in these
patients. Additionally, we recommend that hypertension guidelines should be
updated every 3-4 years with a fresh approach to the definition of target BP
levels, the use of modern technology in the diagnosis of hypertension, and the
treatment of hypertension in special populations not addressed in earlier
guidelines.
PMID- 25114279
TI - Intrapleural lipoma mimicking a lung cancer.
PMID- 25114280
TI - Bell's sign with lagophthalmos in leprosy.
PMID- 25114281
TI - Periprocedural stroke presenting as isolated unilateral internuclear
ophthalmoplegia.
PMID- 25114278
TI - Genetic regulation of Zfp30, CXCL1, and neutrophilic inflammation in murine lung.
AB - Allergic asthma is a complex disease characterized in part by granulocytic
inflammation of the airways. In addition to eosinophils, neutrophils (PMN) are
also present, particularly in cases of severe asthma. We sought to identify the
genetic determinants of neutrophilic inflammation in a mouse model of house dust
mite (HDM)-induced asthma. We applied an HDM model of allergic asthma to the
eight founder strains of the Collaborative Cross (CC) and 151 incipient lines of
the CC (preCC). Lung lavage fluid was analyzed for PMN count and the
concentration of CXCL1, a hallmark PMN chemokine. PMN and CXCL1 were strongly
correlated in preCC mice. We used quantitative trait locus (QTL) mapping to
identify three variants affecting PMN, one of which colocalized with a QTL for
CXCL1 on chromosome (Chr) 7. We used lung eQTL data to implicate a variant in the
gene Zfp30 in the CXCL1/PMN response. This genetic variant regulates both CXCL1
and PMN by altering Zfp30 expression, and we model the relationships between the
QTL and these three endophenotypes. We show that Zfp30 is expressed in airway
epithelia in the normal mouse lung and that altering Zfp30 expression in vitro
affects CXCL1 responses to an immune stimulus. Our results provide strong
evidence that Zfp30 is a novel regulator of neutrophilic airway inflammation.
PMID- 25114282
TI - Scleroderma and breast implants.
PMID- 25114283
TI - Thromboembolic complications in the nephrotic syndrome.
PMID- 25114284
TI - Seeking a better (residency) match.
PMID- 25114285
TI - Metal water bottle causing tongue entrapment in a child.
PMID- 25114286
TI - Health technology assessment: the journey continues.
PMID- 25114288
TI - Inguinal hernia in a 55-year-old man.
PMID- 25114289
TI - Exercise prescriptions endorsed.
PMID- 25114290
TI - Medicare on trial.
PMID- 25114293
TI - Triggering receptor expressed on myeloid cells 2 (TREM2) promotes adipogenesis
and diet-induced obesity.
AB - Triggering receptor expressed on myeloid cells 2 (TREM2) is known to be involved
in the anti-inflammatory response and osteoclast development. However, the role
of TREM2 in adipogenesis or obesity has not yet been defined. The effect of TREM2
on adipogenesis and obesity was investigated in TREM2 transgenic (TG) mice on a
high-fat diet (HFD). To block TREM2 signaling, a neutralizing fusion protein
specific for TREM2 (TREM2-Ig) was used. TG mice were much more obese than wild
type mice after feeding with an HFD, independent of the quantity of food intake.
These HFD-fed TG mice manifested adipocyte hypertrophy, glucose and insulin
resistance, and hepatic steatosis. The expression of adipogenic regulator genes,
such as peroxisome proliferator-activated receptor gamma and CCAAT/enhancer
binding protein alpha, was markedly increased in HFD-fed TG mice. Additionally,
HFD-fed TG mice exhibited decreased Wnt10b expression and increased GSK-3beta
(glycogen synthase kinase-3beta)-mediated beta-catenin phosphorylation. In
contrast, the blockade of TREM2 signaling using TREM2-Ig resulted in the
inhibition of adipocyte differentiation in vitro and a reduction in body weight
in vivo by downregulating the expression of adipogenic regulators. Our data
demonstrate that TREM2 promotes adipogenesis and diet-induced obesity by
upregulating adipogenic regulators in conjunction with inhibiting the Wnt10b/beta
catenin signaling pathway.
PMID- 25114291
TI - Generation of catalytic human Ago4 identifies structural elements important for
RNA cleavage.
AB - Argonaute proteins bind small RNAs and mediate cleavage of complementary target
RNAs. The human Argonaute protein Ago4 is catalytically inactive, although it is
highly similar to catalytic Ago2. Here, we have generated Ago2-Ago4 chimeras and
analyzed their cleavage activity in vitro. We identify several specific features
that inactivate Ago4: the catalytic center, short sequence elements in the N
terminal domain, and an Ago4-specific insertion in the catalytic domain. In
addition, we show that Ago2-mediated cleavage of the noncanonical miR-451
precursor can be carried out by any catalytic human Ago protein. Finally,
phylogenetic analyses establish evolutionary distances between the Ago proteins.
Interestingly, these distances do not fully correlate with the structural changes
inactivating them, suggesting functional adaptations of individual human Ago
proteins.
PMID- 25114292
TI - Clinical and molecular characterization of a novel PLIN1 frameshift mutation
identified in patients with familial partial lipodystrophy.
AB - Perilipin 1 is a lipid droplet coat protein predominantly expressed in
adipocytes, where it inhibits basal and facilitates stimulated lipolysis. Loss-of
function mutations in the PLIN1 gene were recently reported in patients with a
novel subtype of familial partial lipodystrophy, designated as FPLD4. We now
report the identification and characterization of a novel heterozygous frameshift
mutation affecting the carboxy-terminus (439fs) of perilipin 1 in two unrelated
families. The mutation cosegregated with a similar phenotype including partial
lipodystrophy, severe insulin resistance and type 2 diabetes, extreme
hypertriglyceridemia, and nonalcoholic fatty liver disease in both families. Poor
metabolic control despite maximal medical therapy prompted two patients to
undergo bariatric surgery, with remarkably beneficial consequences. Functional
studies indicated that expression levels of the mutant protein were lower than
wild-type protein, and in stably transfected preadipocytes the mutant protein was
associated with smaller lipid droplets. Interestingly, unlike the previously
reported 398 and 404 frameshift mutants, this variant binds and stabilizes ABHD5
expression but still fails to inhibit basal lipolysis as effectively as wild-type
perilipin 1. Collectively, these findings highlight the physiological need for
exquisite regulation of neutral lipid storage within adipocyte lipid droplets, as
well as the possible metabolic benefits of bariatric surgery in this serious
disease.
PMID- 25114295
TI - GLP-1 and exendin-4 transiently enhance GABAA receptor-mediated synaptic and
tonic currents in rat hippocampal CA3 pyramidal neurons.
AB - Glucagon-like peptide-1 (GLP-1) is a hormone that stimulates insulin secretion.
Receptors for GLP-1 are also found in the brain, including the hippocampus, the
center for memory and learning. Diabetes is a risk factor for decreased memory
functions. We studied effects of GLP-1 and exendin-4, a GLP-1 receptor agonist,
on gamma-aminobutyric acid (GABA) signaling in hippocampal CA3 pyramidal neurons.
GABA is the main inhibitory neurotransmitter and decreases neuronal excitability.
GLP-1 (0.01-1 nmol/L) transiently enhanced synaptic and tonic currents, and the
effects were blocked by exendin (9-39). Ten pmol/L GLP-1 increased both the
spontaneous inhibitory postsynaptic current (sIPSC) amplitudes and frequency by a
factor of 1.8. In 0.1, 1 nmol/L GLP-1 or 10, 50, or 100 nmol/L exendin-4, only
the sIPSC frequency increased. The tonic current was enhanced by 0.01-1 nmol/L
GLP-1 and by 0.5-100 nmol/L exendin-4. When action potentials were inhibited by
tetrodotoxin (TTX), inhibitory postsynaptic currents decreased and currents were
no longer potentiated by GLP-1 or exendin-4. In contrast, although the tonic
current decreased in TTX, it was still enhanced by GLP-1 or exendin-4. The
results demonstrate GLP-1 receptor regulation of hippocampal function and are
consistent with GLP-1 receptor agonists enhancing GABAA signaling by pre- and
postsynaptic mechanisms.
PMID- 25114294
TI - Perifornical hypothalamic orexin and serotonin modulate the counterregulatory
response to hypoglycemic and glucoprivic stimuli.
AB - Previous reports suggested an important role for serotonin (5-hydroxytryptamine
[5-HT]) in enhancing the counterregulatory response (CRR) to hypoglycemia. To
elucidate the sites of action mediating this effect, we initially found that
insulin-induced hypoglycemia stimulates 5-HT release in widespread forebrain
regions, including the perifornical hypothalamus (PFH; 30%), ventromedial
hypothalamus (34%), paraventricular hypothalamus (34%), paraventricular thalamic
nucleus (64%), and cerebral cortex (63%). Of these, we focused on the PFH because
of its known modulation of diverse neurohumoral and behavioral responses. In
awake, behaving rats, bilateral PFH glucoprivation with 5-thioglucose stimulated
adrenal medullary epinephrine (Epi) release (3,153%) and feeding (400%), while
clamping PFH glucose at postprandial brain levels blunted the Epi response to
hypoglycemia by 30%. The PFH contained both glucose-excited (GE) and glucose
inhibited (GI) neurons; GE neurons were primarily excited, while GI neurons were
equally excited or inhibited by 5-HT at hypoglycemic glucose levels in vitro.
Also, 5-HT stimulated lactate production by cultured hypothalamic astrocytes.
Depleting PFH 5-HT blunted the Epi (but not feeding) response to focal PFH (69%)
and systemic glucoprivation (39%), while increasing PFH 5-HT levels amplified the
Epi response to hypoglycemia by 32%. Finally, the orexin 1 receptor antagonist
SB334867A attenuated both the Epi (65%) and feeding (47%) responses to focal PFH
glucoprivation. Thus we have identified the PFH as a glucoregulatory region where
both 5-HT and orexin modulate the CRR and feeding responses to glucoprivation.
PMID- 25114296
TI - Contribution of liraglutide in the fixed-ratio combination of insulin degludec
and liraglutide (IDegLira).
AB - OBJECTIVE: Insulin degludec/liraglutide (IDegLira) is a novel combination of
insulin degludec (IDeg) and liraglutide. This trial investigated the contribution
of the liraglutide component of IDegLira versus IDeg alone on efficacy and safety
in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: In a 26-week,
double-blind trial, patients with type 2 diabetes (A1C 7.5-10.0% [58-86
mmol/mol]) on basal insulin (20-40 units) and metformin with or without
sulfonylurea/glinides were randomized (1:1) to once-daily IDegLira + metformin or
IDeg + metformin with titration aiming for fasting plasma glucose between 4 and 5
mmol/L. Maximum allowed doses were 50 dose steps (equal to 50 units IDeg plus 1.8
mg liraglutide) and 50 units for IDeg. The primary end point was change in A1C
from baseline. RESULTS: A total of 413 patients were randomized (mean A1C 8.8%
[73 mmol/mol]; BMI 33.7 kg/m2). IDeg dose, alone or as part of IDegLira, was
equivalent (45 units). A1C decreased by 1.9% (21 mmol/mol) with IDegLira and by
0.9% (10 mmol/mol) with IDeg (estimated treatment difference -1.1% [95% CI -1.3,
0.8], -12 mmol/mol [95% CI -14, -9; P < 0.0001). Mean weight reduction with
IDegLira was 2.7 kg vs. no weight change with IDeg, P < 0.0001. Hypoglycemia
incidence was comparable (24% for IDegLira vs. 25% for IDeg). Overall adverse
events were similar, and incidence of nausea was low in both groups (IDegLira
6.5% vs. IDeg 3.5%). CONCLUSIONS: IDegLira achieved glycemic control superior to
that of IDeg at equivalent insulin doses without higher risk of hypoglycemia and
with the benefit of weight loss. These findings establish the efficacy and safety
of IDegLira and the distinct contribution of the liraglutide component.
PMID- 25114298
TI - At 15 years of follow-up, bariatric surgery, especially when performed within the
first year, is associated with diabetes remission and reduced incidence of
microvascular and macrovascular complications.
PMID- 25114299
TI - Self-harm in young people.
AB - Self-harm is a common problem among young people with many presenting to clinical
services via general hospitals, but many more do not come to the attention of
clinical services at all. Self-harm is strongly associated with completed suicide
so it is extremely important that patients are assessed and treated for this
problem effectively. Despite the scale of the problem in young people, there is a
very limited evidence base on what interventions may help them to recover from
self-harm. The evidence is discussed here and some recommendations are made about
how to engage clinically with young people who self-harm from assessment to
therapeutic intervention.
PMID- 25114300
TI - Cumulative adversity in early childhood is associated with increased BMI and
behavioural problems.
AB - Implications for practice and research: Mental health problems and obesity are
significant outcomes for children experiencing adversity in early life.
Behavioural outcomes and body mass index (BMI) are more consistently reported for
children experiencing adversity in early life compared with blood pressure (BP).
Incomplete data due to drop out over time and a reliance on parental reporting
are challenges for large longitudinal studies; future research directions include
balancing and testing such investigations with smaller in-depth studies.
PMID- 25114301
TI - New approaches to the Moon's isotopic crisis.
AB - Recent comparisons of the isotopic compositions of the Earth and the Moon show
that, unlike nearly every other body known in the Solar System, our satellite's
isotopic ratios are nearly identical to the Earth's for nearly every isotopic
system. The Moon's chemical make-up, however, differs from the Earth's in its low
volatile content and perhaps in the elevated abundance of oxidized iron. This
surprising situation is not readily explained by current impact models of the
Moon's origin and offers a major clue to the Moon's formation, if we only could
understand it properly. Current ideas to explain this similarity range from
assuming an impactor with the same isotopic composition as the Earth to
postulating a pure ice impactor that completely vaporized upon impact. Several
recent proposals follow from the suggestion that the Earth-Moon system may have
lost a great deal of angular momentum during early resonant interactions. The
isotopic constraint may be the most stringent test yet for theories of the Moon's
origin.
PMID- 25114302
TI - Lunar-forming impacts: processes and alternatives.
AB - The formation of a protolunar disc by a giant impact with the early Earth is
discussed, focusing on two classes of impacts: (i) canonical impacts, in which a
Mars-sized impactor produces a planet-disc system whose angular momentum is
comparable to that in the current Earth and Moon, and (ii) high-angular-momentum
impacts, which produce a system whose angular momentum is approximately a factor
of 2 larger than that in the current Earth and Moon. In (i), the disc originates
primarily from impactor-derived material and thus is expected to have an initial
composition distinct from that of the Earth's mantle. In (ii), a hotter, more
compact initial disc is produced with a silicate composition that can be nearly
identical to that of the silicate Earth. Both scenarios require subsequent
processes for consistency with the current Earth and Moon: disc-planet
compositional equilibration in the case of (i), or large-scale angular momentum
loss during capture of the newly formed Moon into the evection resonance with the
Sun in the case of (ii).
PMID- 25114303
TI - Terrestrial aftermath of the Moon-forming impact.
AB - Much of the Earth's mantle was melted in the Moon-forming impact. Gases that were
not partially soluble in the melt, such as water and CO2, formed a thick, deep
atmosphere surrounding the post-impact Earth. This atmosphere was opaque to
thermal radiation, allowing heat to escape to space only at the runaway
greenhouse threshold of approximately 100 W m(-2). The duration of this runaway
greenhouse stage was limited to approximately 10 Myr by the internal energy and
tidal heating, ending with a partially crystalline uppermost mantle and a solid
deep mantle. At this point, the crust was able to cool efficiently and solidified
at the surface. After the condensation of the water ocean, approximately 100 bar
of CO2 remained in the atmosphere, creating a solar-heated greenhouse, while the
surface cooled to approximately 500 K. Almost all this CO2 had to be sequestered
by subduction into the mantle by 3.8 Ga, when the geological record indicates the
presence of life and hence a habitable environment. The deep CO2 sequestration
into the mantle could be explained by a rapid subduction of the old oceanic
crust, such that the top of the crust would remain cold and retain its CO2.
Kinematically, these episodes would be required to have both fast subduction (and
hence seafloor spreading) and old crust. Hadean oceanic crust that formed from
hot mantle would have been thicker than modern crust, and therefore only old
crust underlain by cool mantle lithosphere could subduct. Once subduction
started, the basaltic crust would turn into dense eclogite, increasing the rate
of subduction. The rapid subduction would stop when the young partially frozen
crust from the rapidly spreading ridge entered the subduction zone.
PMID- 25114304
TI - Lunar and terrestrial planet formation in the Grand Tack scenario.
AB - We present conclusions from a large number of N-body simulations of the giant
impact phase of terrestrial planet formation. We focus on new results obtained
from the recently proposed Grand Tack model, which couples the gas-driven
migration of giant planets to the accretion of the terrestrial planets. The giant
impact phase follows the oligarchic growth phase, which builds a bi-modal mass
distribution within the disc of embryos and planetesimals. By varying the ratio
of the total mass in the embryo population to the total mass in the planetesimal
population and the mass of the individual embryos, we explore how different disc
conditions control the final planets. The total mass ratio of embryos to
planetesimals controls the timing of the last giant (Moon-forming) impact and its
violence. The initial embryo mass sets the size of the lunar impactor and the
growth rate of Mars. After comparing our simulated outcomes with the actual
orbits of the terrestrial planets (angular momentum deficit, mass concentration)
and taking into account independent geochemical constraints on the mass accreted
by the Earth after the Moon-forming event and on the time scale for the growth of
Mars, we conclude that the protoplanetary disc at the beginning of the giant
impact phase must have had most of its mass in Mars-sized embryos and only a
small fraction of the total disc mass in the planetesimal population. From this,
we infer that the Moon-forming event occurred between approximately 60 and
approximately 130 Myr after the formation of the first solids and was caused most
likely by an object with a mass similar to that of Mars.
PMID- 25114305
TI - Rb-Sr, Sm-Nd and Lu-Hf isotope systematics of the lunar Mg-suite: the age of the
lunar crust and its relation to the time of Moon formation.
AB - New Rb-Sr, (146,147)Sm-(142,143)Nd and Lu-Hf isotopic analyses of Mg-suite lunar
crustal rocks 67667, 76335, 77215 and 78238, including an internal isochron for
norite 77215, were undertaken to better define the time and duration of lunar
crust formation and the history of the source materials of the Mg-suite. Isochron
ages determined in this study for 77215 are: Rb-Sr=4450+/-270 Ma, (147)Sm
(143)Nd=4283+/-23 Ma and Lu-Hf=4421+/-68 Ma. The data define an initial
(146)Sm/(144)Sm ratio of 0.00193+/-0.00092 corresponding to ages between 4348 and
4413 Ma depending on the half-life and initial abundance used for (146)Sm. The
initial Nd and Hf isotopic compositions of all samples indicate a source region
with slight enrichment in the incompatible elements in accord with previous
suggestions that the Mg-suite crustal rocks contain a component of KREEP. The
Sm/Nd-(142)Nd/(144)Nd correlation shown by both ferroan anorthosite and Mg-suite
rocks is coincident with the trend defined by mare and KREEP basalts, the slope
of which corresponds to ages between 4.35 and 4.45 Ga. These data, along with
similar ages for various early Earth differentiation events, are in accord with
the model of lunar formation via giant impact into Earth at ca 4.4 Ga.
PMID- 25114306
TI - Isotopes as tracers of the sources of the lunar material and processes of lunar
origin.
AB - Ever since the Apollo programme, isotopic abundances have been used as tracers to
study lunar formation, in particular to study the sources of the lunar material.
In the past decade, increasingly precise isotopic data have been reported that
give strong indications that the Moon and the Earth's mantle have a common
heritage. To reconcile these observations with the origin of the Moon via the
collision of two distinct planetary bodies, it has been proposed (i) that the
Earth-Moon system underwent convective mixing into a single isotopic reservoir
during the approximately 10(3) year molten disc epoch after the giant impact but
before lunar accretion, or (ii) that a high angular momentum impact injected a
silicate disc into orbit sourced directly from the mantle of the proto-Earth and
the impacting planet in the right proportions to match the isotopic observations.
Recently, it has also become recognized that liquid-vapour fractionation in the
energetic aftermath of the giant impact is capable of generating measurable mass
dependent isotopic offsets between the silicate Earth and Moon, rendering
isotopic measurements sensitive not only to the sources of the lunar material,
but also to the processes accompanying lunar origin. Here, we review the isotopic
evidence that the silicate-Earth-Moon system represents a single planetary
reservoir. We then discuss the development of new isotopic tracers sensitive to
processes in the melt-vapour lunar disc and how theoretical calculations of their
behaviour and sample observations can constrain scenarios of post-impact
evolution in the earliest history of the Earth-Moon system.
PMID- 25114307
TI - Accretion of the Moon from non-canonical discs.
AB - Impacts that leave the Earth-Moon system with a large excess in angular momentum
have recently been advocated as a means of generating a protolunar disc with a
composition that is nearly identical to that of the Earth's mantle. We here
investigate the accretion of the Moon from discs generated by such 'non
canonical' impacts, which are typically more compact than discs produced by
canonical impacts and have a higher fraction of their mass initially located
inside the Roche limit. Our model predicts a similar overall accretional history
for both canonical and non-canonical discs, with the Moon forming in three
consecutive steps over hundreds of years. However, we find that, to yield a lunar
mass Moon, the more compact non-canonical discs must initially be more massive
than implied by prior estimates, and only a few of the discs produced by impact
simulations to date appear to meet this condition. Non-canonical impacts require
that capture of the Moon into the evection resonance with the Sun reduced the
Earth-Moon angular momentum by a factor of 2 or more. We find that the Moon's
semi-major axis at the end of its accretion is approximately 7R?, which is
comparable to the location of the evection resonance for a post-impact Earth with
a 2.5 h rotation period in the absence of a disc. Thus, the dynamics of the
Moon's assembly may directly affect its ability to be captured into the
resonance.
PMID- 25114297
TI - Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from
the American Heart Association and American Diabetes Association.
PMID- 25114309
TI - Lunar bulk chemical composition: a post-Gravity Recovery and Interior Laboratory
reassessment.
AB - New estimates of the thickness of the lunar highlands crust based on data from
the Gravity Recovery and Interior Laboratory mission, allow us to reassess the
abundances of refractory elements in the Moon. Previous estimates of the Moon
fall into two distinct groups: earthlike and a 50% enrichment in the Moon
compared with the Earth. Revised crustal thicknesses and compositional
information from remote sensing and lunar samples indicate that the crust
contributes 1.13-1.85 wt% Al2O3 to the bulk Moon abundance. Mare basalt Al2O3
concentrations (8-10 wt%) and Al2O3 partitioning behaviour between melt and
pyroxene during partial melting indicate mantle Al2O3 concentration in the range
1.3-3.1 wt%, depending on the relative amounts of pyroxene and olivine. Using
crustal and mantle mass fractions, we show that that the Moon and the Earth most
likely have the same (within 20%) concentrations of refractory elements. This
allows us to use correlations between pairs of refractory and volatile elements
to confirm that lunar abundances of moderately volatile elements such as K, Rb
and Cs are depleted by 75% in the Moon compared with the Earth and that highly
volatile elements, such as Tl and Cd, are depleted by 99%. The earthlike
refractory abundances and depleted volatile abundances are strong constraints on
lunar formation processes.
PMID- 25114308
TI - Understanding the origin and evolution of water in the Moon through lunar sample
studies.
AB - A paradigm shift has recently occurred in our knowledge and understanding of
water in the lunar interior. This has transpired principally through continued
analysis of returned lunar samples using modern analytical instrumentation. While
these recent studies have undoubtedly measured indigenous water in lunar samples
they have also highlighted our current limitations and some future challenges
that need to be overcome in order to fully understand the origin, distribution
and evolution of water in the lunar interior. Another exciting recent development
in the field of lunar science has been the unambiguous detection of water or
water ice on the surface of the Moon through instruments flown on a number of
orbiting spacecraft missions. Considered together, sample-based studies and those
from orbit strongly suggest that the Moon is not an anhydrous planetary body, as
previously believed. New observations and measurements support the possibility of
a wet lunar interior and the presence of distinct reservoirs of water on the
lunar surface. Furthermore, an approach combining measurements of water abundance
in lunar samples and its hydrogen isotopic composition has proved to be of vital
importance to fingerprint and elucidate processes and source(s) involved in
giving rise to the lunar water inventory. A number of sources are likely to have
contributed to the water inventory of the Moon ranging from primordial water to
meteorite-derived water ice through to the water formed during the reaction of
solar wind hydrogen with the lunar soil. Perhaps two of the most striking
findings from these recent studies are the revelation that at least some portions
of the lunar interior are as water-rich as some Mid-Ocean Ridge Basalt source
regions on Earth and that the water in the Earth and the Moon probably share a
common origin.
PMID- 25114310
TI - Contraction or expansion of the Moon's crust during magma ocean freezing?
AB - The lack of contraction features on the Moon has been used to argue that the Moon
underwent limited secular cooling, and thus had a relatively cool initial state.
A cool early state in turn limits the depth of the lunar magma ocean. Recent
GRAIL gravity measurements, however, suggest that dikes were emplaced in the
lower crust, requiring global lunar expansion. Starting from the magma ocean
state, we show that solidification of the lunar magma ocean would most likely
result in expansion of the young lunar crust, and that viscous relaxation of the
crust would prevent early tectonic features of contraction or expansion from
being recorded permanently. The most likely process for creating the expansion
recorded by the dikes is melting during cumulate overturn of the newly solidified
lunar mantle.
PMID- 25114311
TI - Evaporative fractionation of volatile stable isotopes and their bearing on the
origin of the Moon.
AB - The Moon is depleted in volatile elements relative to the Earth and Mars. Low
abundances of volatile elements, fractionated stable isotope ratios of S, Cl, K
and Zn, high MU ((238)U/(204)Pb) and long-term Rb/Sr depletion are distinguishing
features of the Moon, relative to the Earth. These geochemical characteristics
indicate both inheritance of volatile-depleted materials that formed the Moon and
planets and subsequent evaporative loss of volatile elements that occurred during
lunar formation and differentiation. Models of volatile loss through localized
eruptive degassing are not consistent with the available S, Cl, Zn and K isotopes
and abundance data for the Moon. The most probable cause of volatile depletion is
global-scale evaporation resulting from a giant impact or a magma ocean phase
where inefficient volatile loss during magmatic convection led to the present
distribution of volatile elements within mantle and crustal reservoirs. Problems
exist for models of planetary volatile depletion following giant impact. Most
critically, in this model, the volatile loss requires preferential delivery and
retention of late-accreted volatiles to the Earth compared with the Moon.
Different proportions of late-accreted mass are computed to explain present-day
distributions of volatile and moderately volatile elements (e.g. Pb, Zn; 5 to
>10%) relative to highly siderophile elements (approx. 0.5%) for the Earth.
Models of early magma ocean phases may be more effective in explaining the
volatile loss. Basaltic materials (e.g. eucrites and angrites) from highly
differentiated airless asteroids are volatile-depleted, like the Moon, whereas
the Earth and Mars have proportionally greater volatile contents. Parent-body
size and the existence of early atmospheres are therefore likely to represent
fundamental controls on planetary volatile retention or loss.
PMID- 25114312
TI - Heterogeneity in lunar anorthosite meteorites: implications for the lunar magma
ocean model.
AB - The lunar magma ocean model is a well-established theory of the early evolution
of the Moon. By this model, the Moon was initially largely molten and the
anorthositic crust that now covers much of the lunar surface directly
crystallized from this enormous magma source. We are undertaking a study of the
geochemical characteristics of anorthosites from lunar meteorites to test this
model. Rare earth and other element abundances have been measured in situ in
relict anorthosite clasts from two feldspathic lunar meteorites: Dhofar 908 and
Dhofar 081. The rare earth elements were present in abundances of approximately
0.1 to approximately 10* chondritic (CI) abundance. Every plagioclase exhibited a
positive Eu-anomaly, with Eu abundances of up to approximately 20*CI.
Calculations of the melt in equilibrium with anorthite show that it apparently
crystallized from a magma that was unfractionated with respect to rare earth
elements and ranged in abundance from 8 to 80*CI. Comparisons of our data with
other lunar meteorites and Apollo samples suggest that there is notable
heterogeneity in the trace element abundances of lunar anorthosites, suggesting
these samples did not all crystallize from a common magma source. Compositional
and isotopic data from other authors also suggest that lunar anorthosites are
chemically heterogeneous and have a wide range of ages. These observations may
support other models of crust formation on the Moon or suggest that there are
complexities in the lunar magma ocean scenario to allow for multiple generations
of anorthosite formation.
PMID- 25114313
TI - Siderophile element constraints on the origin of the Moon.
AB - Discovery of small enrichments in (182)W/(184)W in some Archaean rocks, relative
to modern mantle, suggests both exogeneous and endogenous modifications to highly
siderophile element (HSE) and moderately siderophile element abundances in the
terrestrial mantle. Collectively, these isotopic enrichments suggest the
formation of chemically fractionated reservoirs in the terrestrial mantle that
survived the putative Moon-forming giant impact, and also provide support for the
late accretion hypothesis. The lunar mantle sources of volcanic glasses and
basalts were depleted in HSEs relative to the terrestrial mantle by at least a
factor of 20. The most likely explanations for the disparity between the Earth
and Moon are either that the Moon received a disproportionately lower share of
late accreted materials than the Earth, such as may have resulted from stochastic
late accretion, or the major phase of late accretion occurred prior to the Moon
forming event, and the putative giant impact led to little drawdown of HSEs to
the Earth's core. High precision determination of the (182)W isotopic composition
of the Moon can help to resolve this issue.
PMID- 25114314
TI - On the evolution of the protolunar disc.
AB - The structure and viscous evolution of a post-impact, protolunar disc is
examined. The equations for a silicate disc in two-phase (vapour-liquid)
equilibrium are employed to derive an analytical solution to vertical structure.
Both a vertically mixed phase disc and a stratified disc, where a magma layer
exists in the mid-plane surrounded by a vapour reservoir, are considered. The
former largely reproduces the low gas mass fraction, x?1, profiles of the disc
described in earlier literature that proposed that the disc would hover on the
brink of gravitational instability. In the latter, the vapour layer has x~1 and
is generally gravitationally stable, while the magma layer is vigorously
unstable. The viscous evolution of the stratified model is then explored.
Initially, the disc quickly settles to a quasi-steady state with a vapour
reservoir containing the majority of the disc mass. The magma layer viscously
spreads on a time scale of approximately 3-4 years, during which vapour
continuously condenses into droplets that settle to the mid-plane, maintaining
the magma surface density in spite of disc spreading. Material flowing inwards is
accreted by the Earth; material flowing outwards past the Roche boundary can
become incorporated into accreting moonlets. This evolution persists until the
vapour reservoir is depleted in approximately 50-100 years, depending on its
initial mass.
PMID- 25114315
TI - The giant impact hypothesis: past, present (and future?).
AB - At the request of editors, this paper offers a historical review of early work on
the giant impact hypothesis, as well as comments on new data. The author hereby
claims (whether believable or not) that his interest is to move towards a correct
model of lunar origin, not to defend a possibly incorrect idea, just because of
being a co-author of a relevant early paper. Nonetheless, the 1974 giant impact
hypothesis appears still to be viable.
PMID- 25114317
TI - The iodine-plutonium-xenon age of the Moon-Earth system revisited.
AB - Iodine-plutonium-xenon isotope systematics have been used to re-evaluate time
constraints on the early evolution of the Earth-atmosphere system and, by
inference, on the Moon-forming event. Two extinct radionuclides ((129)I,
T1/2=15.6 Ma and (244)Pu, T1/2=80 Ma) have produced radiogenic (129)Xe and
fissiogenic (131-136)Xe, respectively, within the Earth, the related isotope
fingerprints of which are seen in the compositions of mantle and atmospheric Xe.
Recent studies of Archaean rocks suggest that xenon atoms have been lost from the
Earth's atmosphere and isotopically fractionated during long periods of
geological time, until at least the end of the Archaean eon. Here, we build a
model that takes into account these results. Correction for Xe loss permits the
computation of new closure ages for the Earth's atmosphere that are in agreement
with those computed for mantle Xe. The corrected Xe formation interval for the
Earth-atmosphere system is [Formula: see text] Ma after the beginning of Solar
System formation. This time interval may represent a lower limit for the age of
the Moon-forming impact.
PMID- 25114316
TI - Geochemical arguments for an Earth-like Moon-forming impactor.
AB - Geochemical evidence suggests that the material accreted by the Earth did not
change in nature during Earth's accretion, presumably because the inner
protoplanetary disc had uniform isotopic composition similar to enstatite
chondrites, aubrites and ungrouped achondrite NWA 5363/5400. Enstatite meteorites
and the Earth were derived from the same nebular reservoir but diverged in their
chemical evolutions, so no chondrite sample in meteorite collections is
representative of the Earth's building blocks. The similarity in isotopic
composition (Delta(17)O, epsilon(50)Ti and epsilon(54)Cr) between lunar and
terrestrial rocks is explained by the fact that the Moon-forming impactor came
from the same region of the disc as other Earth-forming embryos, and therefore
was similar in isotopic composition to the Earth. The heavy delta(30)Si values of
the silicate Earth and the Moon relative to known chondrites may be due to
fractionation in the solar nebula/protoplanetary disc rather than partitioning of
silicon in Earth's core. An inversion method is presented to calculate the Hf/W
ratios and epsilon(182)W values of the proto-Earth and impactor mantles for a
given Moon-forming impact scenario. The similarity in tungsten isotopic
composition between lunar and terrestrial rocks is a coincidence that can be
explained in a canonical giant impact scenario if an early formed embryo (two
stage model age of 10-20 Myr) collided with the proto-Earth formed over a more
protracted accretion history (two-stage model age of 30-40 Myr).
PMID- 25114319
TI - The origin of the Moon. Preface.
PMID- 25114318
TI - Lunar exploration: opening a window into the history and evolution of the inner
Solar System.
AB - The lunar geological record contains a rich archive of the history of the inner
Solar System, including information relevant to understanding the origin and
evolution of the Earth-Moon system, the geological evolution of rocky planets,
and our local cosmic environment. This paper provides a brief review of lunar
exploration to-date and describes how future exploration initiatives will further
advance our understanding of the origin and evolution of the Moon, the Earth-Moon
system and of the Solar System more generally. It is concluded that further
advances will require the placing of new scientific instruments on, and the
return of additional samples from, the lunar surface. Some of these scientific
objectives can be achieved robotically, for example by in situ geochemical and
geophysical measurements and through carefully targeted sample return missions.
However, in the longer term, we argue that lunar science would greatly benefit
from renewed human operations on the surface of the Moon, such as would be
facilitated by implementing the recently proposed Global Exploration Roadmap.
PMID- 25114320
TI - Shortening the culture time in cytogenetic dosimetry using PCC-R assay.
AB - The fast assessment of the dose received by exposed persons is crucial in
radiological accidents, so the 48 h of cell culture in conventional cytogenetic
dosimetry in addition to some limitations after high doses becomes a
disadvantage. The premature chromosome condensation (PCC) assay permits to
analyse enough cells after high radiation exposure, and the score of PCC-R may
reduce the culture time up to 40-42 h. Peripheral whole-blood samples were
exposed to 1-10 Gy of gamma radiation and cultured during 40 and 42 h. No
statistical difference between frequencies was obtained between 40, 42 and 48 h
of culture time, and PCC index decreased with the increase of the dose and
increased with the culture time. The protocol proposed allows reduce the culture
time down to 40 or 42 h when using the PCC-R assay with adequate precision in
dose estimation.
PMID- 25114322
TI - Verified clinical failure with cefotaxime 1g for treatment of gonorrhoea in the
Netherlands: a case report.
AB - We describe the first case of treatment failure of gonorrhoea with a third
generation cephalosporin, cefotaxime 1g intramuscularly, in the Netherlands. The
case was from a high-frequency transmitting population (men having sex with men)
and was caused by the internationally spreading multidrug-resistant gonococcal NG
MAST ST1407 clone. The patient was clinically cured after treatment with
ceftriaxone 500 mg intramuscularly and this is the only third generation
cephalosporin that should be used for first-line empiric treatment of gonorrhoea.
Increased awareness of failures with third generation cephalosporins, enhanced
monitoring and appropriate verification of treatment failures including more
frequent test-of-cures, and strict adherence to regularly updated treatment
guidelines are essential globally.
PMID- 25114321
TI - Conformance of mean glandular dose from phantom and patient data in mammography.
AB - In mammography dosimetry, phantoms are often used to represent breast tissue. The
conformance of phantom- and patient-based mean glandular dose (MGD) estimates was
evaluated mainly from the aspect of diagnostic reference levels. Patient and
phantom exposure data were collected for eight diagnostic and three screening
mammography devices. More extensive assessments were performed for two devices.
The average breast thickness was close to the nationally used reference of 50 mm
in diagnostic (50 mm, SD = 13 mm, n = 5342) and screening (47 mm, SD = 13 mm, n =
395) examinations. The average MGD for all breasts differed by 2% from the MGD
determined for breasts in the limited compressed thickness range of 40-60 mm. The
difference between phantom- and patient-based MGD estimations was up to 30%.
Therefore, phantom measurements cannot replace patient dose data in MGD
determination.
PMID- 25114323
TI - Embolized ductus device extraction and associated iliofemoral artery repair.
AB - Less-invasive methods for nonsurgical closure of a patent ductus arteriosus have
gained popularity as first-line therapy. An 11-year-old girl underwent
percutaneous patent ductus arteriosus closure with a device. The device embolized
into the descending aorta. An attempt at catheter retrieval was complicated by
iliofemoral arterial injury. Subsequent device extraction was performed with
repair of the arterial injury using a tube graft.
PMID- 25114324
TI - Is serotonin a valuable parameter in peripheral arterial disease?
AB - OBJECTIVE: In this study, we aimed to evaluate the relationship of serum
serotonin levels, which are supposed to affect vascular function, to peripheral
arterial disease. METHODS: This prospective study was performed in 70 patients
(57 males, 13 females; mean age 67 +/- 13 years) with peripheral arterial disease
scheduled for surgery and 70 controls (52 males, 18 females; mean age 58 +/- 12
years). RESULTS: The rates of diabetes mellitus and hypertension and the fasting
glucose levels were significantly higher in the peripheral arterial disease group
(p = 0.001). Total, low-density, and high-density cholesterol, triglycerides,
urea, and creatinine levels, and the smoking rate were similar in both groups (p
> 0.05). The serotonin levels were significantly higher in patients with
peripheral vascular disease scheduled for surgery compared to the control group
(p = 0.024). CONCLUSION: The plasma serotonin level is an important parameter in
peripheral arterial disease.
PMID- 25114325
TI - Omento-myoplasty for postpneumonectomy empyema.
PMID- 25114326
TI - Posterior leaflet segment 2 plication in ischemic mitral regurgitation repair.
AB - AIM: To evaluate the medium-term results of plication of posterior leaflet
segment 2 in addition to ring annuloplasty in patients with functional ischemic
mitral regurgitation. METHODS: The study included 136 patients who underwent
mitral valve repair with plication of posterior leaflet segment 2 for ischemic
mitral regurgitation between 2004 and 2012. The direction and correlation of left
ventricle sphericity and tethering area were established by Pearson correlation
analysis in patients with or without recurrent mitral regurgitation in the medium
term. RESULTS: Medium-term survival was 91.9% and freedom from moderate or severe
mitral regurgitation was 89.6%. In medium-term follow-up, transthoracic
echocardiography found a significant decrease in tethering area, coaptation
height, and distance between the commissures compared to the pre-surgery values
(p = 0.0001 in all). The distance between the papillary muscles was reduced
compared to the pre-surgery period but it was not significant (p = 0.204).
Pearson correlation analysis found no significant correlation between the
tethering area and left ventricle sphericity in patients without recurrent mitral
regurgitation (r = 0.15, p = 0.36), a highly positive correlation (r = 0.44, p <
0.001) in patients with mild recurrent mitral regurgitation, and a moderately
positive correlation (r = 0.71, p < 0.01) in patients with moderate or severe
recurrent mitral regurgitation. CONCLUSIONS: The tethering area, coaptation
height, and distance between the commissures decreased significantly, thus
posterior leaflet segment 2 plication in addition to ring annuloplasty may be the
optional procedure to ensure freedom from moderate or severe mitral
regurgitation.
PMID- 25114327
TI - Serial hemodynamic measurements in post-cardiac arrest cardiogenic shock treated
with therapeutic hypothermia.
AB - AIMS: Mortality from cardiogenic shock complicating acute myocardial infarction
(MI) remains high despite contemporary treatment. Therapeutic Hypothermia (TH)
offers cardiovascular and systemic effects that may prove beneficial in this
population, however, current data are limited. This study sought to evaluate the
effect of therapeutic hypothermia on serial hemodynamics obtained in subjects
with post-cardiac arrest cardiogenic shock. METHODS: We analyzed serial
hemodynamics of 14 consecutive patients with cardiogenic shock after cardiac
arrest treated with TH. Study inclusion required baseline hemodynamics obtained
prior to initiation of TH confirming cardiogenic shock defined as cardiac index
<=2.2 L/min/m(2) with a systolic blood pressure of <=90 mmHg, a vasopressor
requirement, or need for mechanical circulatory support. RESULTS: In our 14
patients, the mean age was 58 +/- 13.1 years, mean ejection fraction was 21 +/-
8%, six had an acute MI, 12 required vasopressors, and 10 required mechanical
support prior to initiation of TH. When compared to baseline, patients had
significant improvements in Fick cardiac index, mixed venous O2 saturations, and
serum lactate concentrations while heart rate was reduced following initiation of
TH. There was no significant change in mean arterial pressure, however
vasopressor requirement was reduced. CONCLUSIONS: In patients with cardiogenic
shock following cardiac arrest, initiation of TH was associated with favorable
changes in invasive hemodynamics suggesting safety in this population. Given
potential for favorable hemodynamic and systemic effects of TH in cardiogenic
shock, further prospective study of TH as a potentially novel adjunctive therapy
to early reperfusion in post-MI cardiogenic shock should be considered.
PMID- 25114328
TI - Impact of out-of-hospital cardiac arrest due to ventricular fibrillation in
patients with ST-elevation myocardial infarction admitted for primary
percutaneous coronary intervention: Impact of ventricular fibrillation in STEMI
patients.
AB - OBJECTIVE: Pre-hospital life-threatening ventricular tachycardia/fibrillation
(VT/VF) is relatively common in the acute phase of ST-elevation myocardial
infarction (STEMI). We evaluated the prognostic impact of out-of-hospital cardiac
arrest (OHCA) due to VT/VF in non-selected patients with STEMI admitted for
primary percutaneous coronary intervention (PCI). METHODS: Prospective hospital
registry was used to collect data of consecutive STEMI patients admitted to our
hospital between 2005 and 2010. Patients with OHCA were identified from this
registry, and their medical records were reviewed. RESULTS: During the study
period, 4653 patients were admitted with STEMI. Data regarding OHCA due to VT/VF
was available in 4643 patients (99.8%). A total of 326 patients (7.0%) had OHCA
due to VT/VF. Patients with OHCA were younger (60.3 +/- 11.8 vs. 64.1 +/- 12.9
year, p<0.001), less often had diabetes (5.2% vs. 12.4%, p<0.001) but more often
presented with signs of heart failure (Killip class >1:17.5% vs. 7.7%, p<0.001)
and cardiogenic shock (29.6% vs. 2.5%, p<0.001). Coronary angiography was
performed in 97.5% of the patients. Coronary angiography and primary PCI were
performed equally in both groups. In patients with OHCA, the left main artery
(2.3% vs. 1.0%, p=0.04) and LAD (49.2% vs. 41.2%, p=0.01) were more often the
culprit artery. In-hospital mortality was significantly higher among patients
with OHCA (13.80% vs. 3.4%, p<0.001). However, in patients who were discharged
alive from the hospital, the one-year mortality and the combined incidence of
death and appropriate ICD therapy were similar in patients with and without OHCA.
CONCLUSION: In a large non-selected STEMI patient population admitted for primary
PCI, OHCA due to VT/VF was associated with higher in-hospital mortality but did
not affect the long-term prognosis.
PMID- 25114329
TI - Excellence in acute cardiac care: an overview of the seminar proceedings.
PMID- 25114330
TI - Non-contact multi-particle annular patterning and manipulation with ultrasound
microbeam.
AB - Multiparticle-trapping offers diverse opportunities and applications in
biotechnology. It can be applied to creating various functional materials or
organizing reactive particles. In this paper, we demonstrate that it is possible
to trap and manipulate multi-particles in an annular pattern with a 24 MHz
focused ring-type single element ultrasound transducer. Acoustic ring trap can be
useful in undertaking biotropism studies due to an equal-distance condition from
the center. Also, this ring trap could serve as a force shield to protect
analysis area from other cells. The experimental results showed the capability of
the proposed method as a multi-cell manipulator in formatting specific patterns
of small cells like sperms.
PMID- 25114331
TI - Determination of full set material constants of [011]c poled 0.72Pb(Mg1/3Nb2/3)O3
0.28PbTiO3 single crystal from one sample.
AB - 0.72Pb(Mg1/3Nb2/3)O3-0.28PbTiO3 single crystals poled along [011]c have
macroscopic orthorhombic mm2 symmetry. There are total 17 independent material
coefficients for this symmetry so that the determination of self-consistent full
matrix data is extremely difficult because many samples are needed and there is a
large property variation from sample to sample. To overcome this self-consistency
difficulty, we have developed a combined ultrasonic pulse-echo and impedance
spectroscopy method, which can extract all coefficients from only one small
sample. This method is especially useful for piezoelectric materials whose
properties are strongly dependent on geometry and for crystals with only limited
size available.
PMID- 25114332
TI - Synthesis of mono-dispersed nanofluids using solution plasma.
AB - Small-sized and well-dispersed gold nanoparticles (NPs) for nanofluidics have
been synthesized by electrical discharge in liquid environment using termed
solution plasma processing (SPP). Electrons and the hydrogen radicals are
reducing the gold ions to the neutral form in plasma gas phase and liquid phase,
respectively. The gold NPs have the smallest diameter of 4.9 nm when the solution
temperature was kept at 20 degrees C. Nucleation and growth theory describe the
evolution of the NP diameter right after the reduction reaction in function of
the system temperature, NP surface energy, dispersion energy barrier, and
nucleation rate. Negative charges on the NPs surface during and after SPP
generate repulsive forces among the NPs avoiding their agglomeration in solution.
Increasing the average energy in the SPP determines a decrease of the zeta
potential and an increase of the NPs diameter. An important enhancement of the
thermal conductivity of 9.4% was measured for the synthesized nanofluids
containing NPs with the smallest size.
PMID- 25114333
TI - Significance of coarse cereals in health and nutrition: a review.
AB - This review assesses the nutritional attributes of coarse cereals and also their
utilization as food and as formulated foods. These cereals are laden with
phytochemicals including phenolic acids, tannins, anthocyanins, phytosterols,
avenenathramides and policosanols. They possess high antioxidant properties in
vitro than staple cereals and fruits by different purported pathways. There are
also some anti-nutritional factors that may be reduced by certain processing
treatments. Several epidemiological studies show that these cereals are helpful
in reducing several kinds of chronic diseases like cancers, cardiovascular
diseases, type II diabetes and various gastrointestinal disorders. Being coarse
in nature, they cannot replace our staple cereals, but can be used in different
proportions with rice and wheat to formulate various nutritional products. They
can be used to make porridges, biscuits, cakes, cookies, tortillas, bread,
probiotic drinks, ladoo, ghatta, flakes and several fermented foods. The coarse
cereals also have good potential in manufacturing bioethanol, paper, oil and
biofilms.
PMID- 25114334
TI - Nutritional quality of fresh and heated Aleppo pine (Pinus halepensis Mill.) seed
oil: trans-fatty acid isomers profiles and antioxidant properties.
AB - Numerous studies have focused on trans fatty acids (TFA) technologically produced
by partial hydrogenation of oils. However, TFA can also be present in fresh oils.
For this reason, cis fatty acid (CFA), TFA and conjugated linoleic acid (CLA) of
fresh and heated Aleppo pine seed oil (APSO) at frying temperature (180 degrees
C) were evaluated and correlated with the antioxidant characteristics. Results
showed that fresh APSO had a low oleic/linoleic ratio O/L (0.4). Total TFA in
fresh APSO reached 1%. The predominant TFA was 18:2 n-6 (t9, t12) in both fresh
and heated APSO. Individual TFA increased with significant differences (p < 0.05)
with heating time. CLA occurred after 4 h and significantly increased (p < 0.05)
accounting 10% of total TFA after 10 h. Total TFA are negatively correlated with
alpha-tocopherol, gamma-tocopherol (p < 0.05) and carotenoids (p < 0.01) and
positively correlated with remaining DPPH. Oil stability index (OSI) showed
significant negative correlation with TFA (r = -0.925; p = 0.008). A principal
component analysis (PCA) showed a clear discrimination between fresh and heated
oils. Temperature, heating time, unsaturation degree and antioxidants are
combined factors which significantly affect the isomerization rate and
nutritional quality of APSO.
PMID- 25114335
TI - Characterization and storage stability of the extract of Thai mango (Mangifera
indica Linn. Cultivar Chok-Anan) seed kernels.
AB - Qualitative analysis of hydrolysable extract from mango (Mangifera indica Linn.
cultivar Chok-Anan) seed kernel was performed by means of reversed phase high
performance liquid chromatography coupled to diode array detection and
electrospray ionization mass spectrometry (RPHPLC-DAD-ESI-MS). The main phenolic
compound was identified as methyl gallate by comparing their retention time, UV
vis absorption spectra and mass spectra with a reference standard. Quantification
of phenolic compounds was performed by HPLC-DAD, which revealed that the extract
contained total phenolics at a concentration of 194.1 mg GAE/g dry weight of
mango seed kernel (MSK), of which 85.7% was identified as methyl gallate. In
addition, the antioxidant activities of the extract and the main compound were
assessed by the 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis (3
ethylbenzothiazoline-6-sulfonic acid) assays, by the ferric thiocyanate method
and by an assay of metal chelating activity. Tyrosinase inhibition was also
investigated. Furthermore, the antioxidant capacity and the total phenolic
content of MSK extract stored in a plastic (polyethylene) PE bag decreased during
storage at freezing (-20 degrees C), refrigerated (7 degrees C) and room (28-32
degrees C) temperature for 182 days. The loss of antioxidant capacity and total
phenolic content increased at higher storage temperatures for more than 182 days.
PMID- 25114336
TI - Modification of wheat starch with succinic acid/acetanhydride and azelaic
acid/acetanhydride mixtures. II. Chemical and physical properties.
AB - The aim of this research was to investigate the influence of modification with
succinic acid/acetanhydride and azelaic acid/acetanhydride mixtures on chemical
and physical properties of wheat starch. Starch was isolated from two wheat
varieties and modified with mixtures of succinic acid and acetanhydride and
azelaic acid and acetanhydride in 4, 6 and 8% (w/w). Total starch content,
resistant starch content, degree of modification, changes in FT-IR spectra,
colour, gel texture and freeze-thaw stability were determined. Results showed
that resistant starch content increased by both investigated modifications, and
degree of modification increased proportionally to amount of reagents used. FT-IR
analysis of modified starches showed peak around 1,740 cm(-1), characteristic for
carbonyl group of ester. Total colour difference caused by modifications was
detectable by trained people. Adhesiveness significantly increased, while freeze
thaw stability decreased by both investigated modifications.
PMID- 25114337
TI - Chemical composition, molecular weight distribution, secondary structure and
effect of NaCl on functional properties of walnut (Juglans regia L) protein
isolates and concentrates.
AB - Chemical composition, molecular weight distribution, secondary structure and
effect of sodium chloride concentration on functional properties of walnut
protein isolates, concentrates and defatted walnut flour were study. Compared
with walnut protein concentrates (75.6%) and defatted walnut flour (52.5%),
walnut protein isolates contain a relatively high amount of protein (90.5%). The
yield of walnut protein isolates and concentrates was 43.2% and 76.6%,
respectively. In molecular weight distribution study, Walnut protein isolates
showed one peak with molecular weight of 106.33 KDa (100%) and walnut protein
concentrates showed four peaks with molecular weight of 16,725 KDa (0.8%),104.943
KDa(63.9%), 7.3 KDa (11.4%), 2.6 KDa (23.9%). The secondary structure of walnut
protein isolates was similar to that of walnut protein concentrates, but was
differ from that of defatted walnut flour. The addition of sodium chloride (0 ~ 1
M) could improve the functionality of walnut protein concentrates, isolates and
defatted walnut flour. The maximum solubility, water absorption capacity,
emulsifying properties and foaming properties of walnut protein isolates,
concentrates and defatted walnut flour were at sodium chloride solutions of 1.0
M, 0.6 M, 0.4 M, 0.6 M, respectively. The solubility of walnut protein
concentrates (32.5%) in distilled water with 0 M sodium chloride was lower than
that of walnut protein isolates (35.2%). The maximum solubility of walnut protein
isolates, concentrates and defatted walnut flour in solution were 36.8%, 33.7%
and 9.6% at 1.0 M sodium chloride solutions, respectively. As compared with other
vegetable proteins, walnut protein isolates and concentrates exhibited better
emulsifying properties and foam stability.
PMID- 25114338
TI - Important nutritional constituents, flavour components, antioxidant and
antibacterial properties of Pleurotus sajor-caju.
AB - Oyster mushroom (Pleurotus sajor-caju) cultivated in the laboratory was studied
for nutritional constituents, flavor components, antioxidant and antibacterial
properties. Nutritional constituents estimated per 100 g dry weight (d.w.)
include protein (29.3 g), carbohydrate (62.97 g), crude fat (0.91 g), ash (6.82
g) and crude fiber (12.3 g). Energy value of this mushroom was about 297.5
kcal/100 g d.w. Major mineral components estimated include Ca, Fe, and Mg with
highest level of 505.0, 109.5 and 108.7 mg/100 g respectively. Methanolic extract
containing significant amounts of phenols and flavonoids showed free radical
scavenging potential and antibacterial activities against various spp. of Gram
positive and Gram negative bacteria. Compounds responsible for antibacterial
activities analyzed by GC-MS include beta- Sistosterol, Cholestanol, 1,5
Dibenzoylnaphthalene and 1,2-Benzenedicarboxylic acid. Flavor components
extracted by hot extraction method were found to be higher in number and
concentration than the cold extraction method. The characteristic flavor
component of mushroom i.e. 1-Octen-3-ol was better extracted by hot than the
cold.
PMID- 25114339
TI - Efficacy of pink guava pulp as an antioxidant in raw pork emulsion.
AB - Lipid oxidation-induced quality problems can be minimized with the use of natural
antioxidants. The antioxidant potential of pink guava pulp (PGP) was evaluated at
different levels (0%; C, 5.0%; T-1, 7.5%; T-2 and 10.0%; T-3) in the raw pork
emulsion during refrigerated storage of 9 days under aerobic packaging. Lycopene
and beta-carotene contents increased (P < 0.05) with PGP levels. The redness (a*)
increased (P < 0.05), whereas L*decreased (P < 0.05) with the incorporation of
PGP. The visual colour and odour scores were greater (P < 0.05) in PGP-treated
products than control. Percent metmyoglobin formation was greater (P < 0.05) in
the control than PGP-treated products, and increased (P < 0.05) during storage in
all the treatments. Overall, peroxide value, thiobarbituric acid reactive
substances and free fatty acid values were lower (P < 0.05) in PGP-treated raw
emulsion than control throughout storage period. Our results indicated that pink
guava pulp can be utilized as antioxidants in raw pork products to minimize lipid
oxidation, off-odour development, and surface discolouration.
PMID- 25114340
TI - Optimization of ingredients for noodle preparation using response surface
methodology.
AB - In the present investigation, the composite flour combinations using whole wheat
flour (X1), tapioca flour (X2) and defatted soy flour (X3) for the noodle
preparation were made through central composite rotatable design (CCRD). The
analyzed responses were bulk density (BD), proximate composition, water uptake
ratio (WUR), cooking volume expansion (VE), water absorption capacity (WAC),
swelling capacity (SC), gruel solid loss (GSL), and sensory characteristics. A
second order quadratic polynomial equation was fitted to the data of all
responses for prediction. The maximum protein content of 16 g% was achieved by
the combination of 75.54 g of whole wheat flour, 10 g of tapioca flour and 19.78
g of defatted soy flour. Since the inclusion of defatted soy flour >10 g resulted
negative influence on good quality determining responses, the Chinese salted
noodles of excellent quality with maximum WAC, WUR, VE, SC, protein,
carbohydrate, ash and minimum GSL, BD, fat, moisture could be made from ratio of
combination of three independent variables at 77.33 g (X1): 22.19 g (X2): 8.92 g
(X3) respectively. The cost of production per kg of noodles with optimum level of
ingredient was Rs.75.50/-.
PMID- 25114341
TI - Study of chemical properties and evaluation of collagen in mantle, epidermal
connective tissue and tentacle of Indian Squid, Loligo duvauceli Orbigny.
AB - The chemical composition and evaluation of Indian squid (Loligo duvauceli)
mantle, epidermal connective tissue and tentacle is investigated in this current
study. It is observed that squid mantle contains 22.2% total protein; 63.5% of
the total protein is myofibrillar protein. The unique property of squid
myofibrillar protein is its water solubility. Squid mantle contains 12.0% total
collagen. Epidermal connective tissue has highest amounts of total collagen
(17.8%). SDS-PAGE of total collagen identified high molecular weight alpha-, beta
and gamma- sub-chains. Amino acid profile analysis indicates that mantle and
tentacle contain essential amino acids. Arginine forms a major portion of mantle
collagen (272.5 g/100 g N). Isoleucine, glutamic acid and lysine are other amino
acids that are found in significantly high amounts in the mantle. Sulphur
containing cystine is deficit in mantle collagen. Papain digest of mantle and
epidermal connective tissue is rich in uronic acid, while papain digest,
collagenase digest and urea digest of epidermal connective tissue has significant
amounts of sialic acid (25.2, 33.2 and 99.8 MUmol /100 g, respectively). PAS
staining of papain digest, collagenase digest and urea digest also identify the
association of hexoses with low molecular weight collagen fragments.
Histochemical sectioning also emphasized the localized distribution of collagen
in epidermal and dermal region and very sparse fibres traverse the myotome
bundles.
PMID- 25114342
TI - Suitability of spring wheat varieties for the production of best quality pizza.
AB - The selection of appropriate wheat cultivars is an imperative issue in product
development and realization. The nutritional profiling of plants and their
cultivars along with their suitability for development of specific products is of
considerable interests for multi-national food chains. In this project, Pizza-Hut
Pakistan provided funds for the selection of suitable newly developed Pakistani
spring variety for pizza production. In this regard, the recent varieties were
selected and evaluated for nutritional and functional properties for pizza
production. Additionally, emphasis has been paid to assess all varieties for
their physico-chemical attributes, rheological parameters and mineral content.
Furthermore, pizza prepared from respective flour samples were further evaluated
for sensory attributes Results showed that Anmool, Abadgar, Imdad, SKD-1, Shafaq
and Moomal have higher values for protein, gluten content, pelshenke value and
SDS sedimentation and these were relatively better in studied parameters as
compared to other varieties although which were considered best for good quality
pizza production. TD-1 got significantly highest score for flavor of pizza and
lowest score was observed from wheat variety Kiran. Moreover, it is concluded
from current study that all wheat varieties except TJ-83 and Kiran exhibited
better results for flavor.
PMID- 25114343
TI - Quality indices of the set-yoghurt prepared from bovine milk treated with
horseradish peroxidase.
AB - Horseradish peroxidase (HRP, EC 1.11.1.7) was applied to treat whole bovine milk
in the presence or absence of ferulic acid (FA). The treated milk exhibited
different rheological properties from the control milk, and was used to prepare
set-yoghurt with commercial direct vat set starter. Some chemical, textural and
rheological properties of the yoghurt prepared were measured and compared.
Compared to that prepared with the control milk, the yoghurt prepared with the
HRP- or HRP and FA-treated bovine milk exhibited an increased hardness and
adhesiveness, lower syneresis extent, higher apparent viscosity, and higher
storage modulus and viscous modulus. Observation of the microstructure of the
yoghurt samples under scanning electron microscopy illustrated that HRP treatment
of bovine milk led to the prepared yoghurt a more compact and uniform structure.
The results in the present work stated that treatment of bovine milk with HRP in
the presence of ferulic acid could be applied to improve the quality of set
yoghurt.
PMID- 25114344
TI - In vitro free radical scavenging and DNA damage protective property of Coriandrum
sativum L. leaves extract.
AB - Coriandrum sativum L. (coriander), an everyday spice in the Indian kitchen is
known to add flavor to the cuisine. It is an annual herb belonging to the
Apiaceae (Umbellifera) family. The hydro-alcohol extract of Coriandrum sativum L.
at the dose of 1 mg/ml was subjected to a series of in vitro assays viz. 2, 2'-
diphenyl-1-picrylhydrazyl, lipid peroxidation by thiobarbituric acid, reducing
power and nitric oxide (NO) radical scavenging in order to study its antioxidant
efficacy in detail. The amount of flavonoids in 70% ethanol extract was found to
be 44.5 MUg and that of the total phenols was 133.74 MUg gallic acid equivalents
per mg extract. The extracts of the leaves showed metal chelating power, with
IC50 values, 368.12 MUg/ml where as that of standard EDTA was 26.7 MUg/ml. The
IC50 values for 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid radical
scavenging was 222 MUg/ml where as that of standard ascorbic acid was 22.6
MUg/ml. The NO scavenging activity of the extract of the leaves showed IC50 value
of 815.6 MUg/ml; at the same time the standard BHA had 49.1 MUg/ml. All the plant
extracts provided DNA damage protection; however, the protection provided at the
dose of 8 MUg/ml was comparable to that of standard gallic acid. The Coriandrum
sativum leaf extract was able to prevent in vitro lipid peroxidation with IC50
values; 589.6 MUg/ml where as that of standard BHA was 16.3 MUg/ml. Our results
also showed significant ferric reducing power indicating the hydrogen donating
ability of the extract. This study indicated the potential of the leaf extract as
a source of natural antioxidants or nutraceuticals that could be of use in food
industry with potential application to reduce oxidative stress in living system.
PMID- 25114345
TI - Drying kinetics and physico-chemical characteristics of Osmo- dehydrated Mango,
Guava and Aonla under different drying conditions.
AB - Mango (Mangiferra indica L), guava (Psiduim guajava L.) slices and aonla (Emblica
officinalis L) segments were osmo-dried under four different dying conditions
viz., cabinet drier (CD), vacuum oven drier (VOD), low temperature drier (LTD)
and solar drier (SD) to evaluate the best drying condition for the fruits. It was
found that vacuum oven drying was superior to other mode of drying as it holds
maximum nutrients like acidity, ascorbic acid, sugar and water removal and
moisture ratio of products. It was found through regression analysis that drying
ratio and rehydration ratio was also superior in vacuum drying followed by
cabinet drying. In addition, descriptive analysis on sensory score was also found
best with vacuum drying while the Non-enzymatic browning (NEB), which is
undesirable character on dried product, was more with solar drier.
PMID- 25114346
TI - Antioxidant potential of thuja (Thuja occidentalis) cones and peach (Prunus
persia) seeds in raw chicken ground meat during refrigerated (4 +/- 1 degrees C)
storage.
AB - The antioxidant activity of thuja (Thuja occidentalis) cones extract (TCE) and
peach (Prunus armeniaca) seeds extract (PSE) were estimated by DPPH free radical
scavenging activity method. Total phenolics, total flavonoids and reducing power
were also estimated in these extracts. Antioxidant potential of these by products
was also evaluated in raw chicken ground meat (GM) during refrigerated (4 +/- 1
degrees C) storage. Total phenolics in TCE and PSE were 7.80 +/- 0.04 and 1.92 +/
0.04 mg TAE/gdw respectively. Both extract also showed remarkable DPPH radical
scavenging activity (25.52 +/- 1.92% and 24.99 +/- 0.32%). The reducing
powerOD700 was observed more in TCE as compared to PSE (3.32 +/- 0.01 and 0.49 +/
0.01). Total flavonoids contents were 7.48 +/- 0.02 and 0.85 +/- 0.01 mg CE/gdw
respectively. Addition of these extract significantly (P < 0.01) affected cooking
losses and WHC of GM. During refrigerated storage (4 degrees C) the TBARS values
at 8 d were significantly (P < 0.01) more in control than TCE and PSE treated
groups.
PMID- 25114347
TI - Effects of gamma irradiation and/or cooking on nutritional quality of faba bean
(Vicia faba L.) cultivars seeds.
AB - The effect of gamma irradiation (0.5 and 1.0 kGy) and/or cooking on the proximate
composition, mineral content, tannin content, phytic acid content and the in
vitro protein digestibility (IVPD) of two Sudanese faba bean cultivars (BB7-S1
and SH-S2) was investigated in the present study. The results obtained revealed
that gamma irradiation and/or cooking treatments have slight effect in chemical
composition and mineral content, while they caused significant (P <= 0.05)
reduction on tannin content for both cultivars. Cooking of faba bean seeds also
insignificantly (P <= 0.05) reduced phytic acid content for both cultivars, while
irradiation process and/or cooking had fluctuated effect. For both cultivars,
irradiation of seeds and/or cooking increased the in vitro protein digestibility
(IVPD), with maximum value of IVPD (79.97%) obtained for cultivar BB7-S1. The
results indicate that the treatments used in this study might improve the
nutritive quality of faba bean seed due to reduction in antinutritional factors
with a concomitant increase in IVPD.
PMID- 25114348
TI - Quality of osmotically pre-treated and vacuum dried pineapple cubes on storage as
influenced by type of solutes and packaging materials.
AB - The quality and stability of osmotically pre-treated and subsequently vacuum
dried pineapple cubes using three different solutes and packed in three different
types of packaging materials on storage was evaluated. The experiment was laid
out in completely randomized block design with two factors and three replications
for each treatment. Treatment combinations were considered as one factor and
storage interval as another factor. Pineapple cubes stored in glass bottle showed
very little percentage variation in moisture content due to its high moisture
barrier properties. In all treatment combination, acidity values were invariably
found to increase as the storage progressed. For all three different osmotic
treatments, HDPE pouch packet always showed highest acidity followed by PVDC
pouch. Again among three solutes under consideration, invert sugar recorded a
rapid increase in acidity than other solutes. In pineapple cubes osmotically
treated with sucrose solution, the rates of decrease of total sugar content were
lower than that of invert sugar and sorbitol treated pineapple cubes. The
percentage decrease of total sugar content was highest when the osmotically
dehydrated pineapple cubes were packed in HDPE pouch and it was least in glass
bottles. There was a gradual decrease in ascorbic acid content with the extension
of storage period and this decrease was statistically significant at all storage
intervals up to six-month. Lowest value of ascorbic acid content (15.210 mg per
100 g initial solid) was recorded in invert sugar treated pineapple cube packed
in HDPE pouch after 6 months of storage.
PMID- 25114349
TI - Synbiotic yogurt-ice cream produced via incorporation of microencapsulated
lactobacillus acidophilus (la-5) and fructooligosaccharide.
AB - Yogurt-ice cream is a nutritious product with a refreshing taste and durability
profoundly longer than that of yogurt. The probiotic Lactobacillus acidophilus
(La-5) cells either in free or encapsulated form were incorporated into yog-ice
cream and their survivability were studied. Fructooligosaccharide (FOS) as a
prebiotic compound at three levels (0, 4 & 8 % w/w) was added to yogurt-ice cream
mix and its effects on some chemical properties, overrun and firmness of product
were evaluated. The higher the incorporated FOS concentration, the lower were the
pH value and higher the total solid content of treatments. FOS incorporation (8
%) significantly increased the overrun of treatments and reduced their firmness.
The viable counts of free probiotics decreased from ~9.55 to ~7.3 log cfu/g after
60 days of frozen storage while that of encapsulated cells merely decreased less
than 1 log cycle. Encapsulation with alginate microbeads protected the probiotic
cells against injuries in the freezing stage as well as, during frozen storage.
PMID- 25114350
TI - Homogenate extraction of gardenia yellow pigment from Gardenia Jasminoides Ellis
fruit using response surface methodology.
AB - Homogenate extraction technology was developed for extraction of gardenia yellow
pigment from Gardenia jasminoides Ellis fruit. The operating parameters affecting
the color value of gardenia yellow pigment were studied on the basis of a Box
Behnken design and response surface methodology. Results showed that the optimum
extraction conditions were as follows: extraction time 41 s, ethanol
concentration 50 %, ratio of liquid to material 15:1 (mL:g) and particle size 1.7
mm. Under the optimum condition, the experimental color value was 52.37 g(-1),
which was in keeping with the predicted one. Compared with the heat extraction
method, the color value of gardenia yellow pigment of homogenate extraction was
higher and the extraction time was shorter. Homogenate extraction method is an
ideal means for extraction of gardenia yellow pigment from Gardenia jasminoides
Ellis fruit.
PMID- 25114351
TI - Effect of different preservative treatments on the shelf-life of sorghum malt
based fermented milk beverage.
AB - Studies were conducted to extend the shelf life of sorghum based fermented milk
beverage (referred to SSL) developed at our Institute. In the first approach
preservatives namely nisin (N) @ 400RU/ml, MicroGARD (M) @ (1%), potassium
sorbate (PS) @ (0.15%) were added to the beverage before packaging and in the
second approach thermization (65 degrees C/5 min) of the packaged samples
containing above mentioned preservatives was adopted. The shelf life was assessed
on the basis of sensory, physico-chemical and microbiological parameters. Total
plate count and lactic acid bacterial count increased till 7th day of storage and
afterwards decreased significantly (p < 0.01). Yeasts and molds count increased
significantly (p < 0.01) throughout the storage period and the rate of increase
was lowest in samples containing PS. Samples containing PS, N and M were found
sensorily acceptable up to 35, 28 and 21 days, respectively. Though the
thermization treatment helped in improving the microbiological and chemical
quality of the beverage, the sensory and physical quality was adversely affected.
Addition of PS without thermization was found to be the best preservation
technique for enhancing the shelf life of SSL at refrigeration conditions.
PMID- 25114352
TI - Effect of cheese as a fat replacer in fermented sausage.
AB - The effects of beef fat substitution with kashar cheese were studied in
traditional Turkish fermented sausage; sucuk. Six sucuk formulations were
prepared by replacing 0, 10, 20, 30, 40 and 50% of beef fat was substituted with
kashar cheese. The fat substitution of fat with kashar cheese decreased fat
content and increased protein content of the product that affected the chemical,
physical and sensorial characteristics of products. Saturated fatty acid content
increased and unsaturated, mono-unsaturated and poly-unsaturated fatty acids
amount were decreased as the cheese amount increased. The formulation with 10%
substitution of beef fat with cheese took the best sensory overall acceptability
scores followed by 20% and control groups.
PMID- 25114353
TI - Extracellular chitin deacetylase production in solid state fermentation by native
soil isolates of Penicillium monoverticillium and Fusarium oxysporum.
AB - Extracellular chitin deacetylase production by native soil isolates of
Penicillium monoverticillium CFR 2 and Fusarium oxysporum CFR 8 in solid state
fermentation (SSF) using commercial wheat bran (CWB) and shrimp processing by
products (SPP) as solid substrate has been studied. P. monoverticillium produced
maximum chitin deacetylase activity of 547.7 +/- 45 and 390.2 +/- 31 units/g
initial dry substrate (U/g IDS) at 96 h of incubation in CWB and SPP media,
respectively. While, F. oxysporum produced maximum chitin deacetylase activity of
306.4 +/- 22 U/g IDS at 72 h of incubation in CWB medium and 220.1 +/- 20 U/g IDS
at 120 h of incubation in SPP medium. Along with chitin deacetylase, P.
monoverticillium and F. oxysporum produced other chitin degrading enzymes such as
endo-chitinase and beta-N-acetylhexosaminidase. P. monoverticillium produced
maximum activity (U/g IDS) of endo-chitinase 4.6 +/- 0.20 at 120 h incubation and
beta-N-acetylhexosaminidase 82.6 +/- 03 at 120 h incubation in CWB medium. While,
F. oxysporum produced maximum activity (U/g IDS) of endo-chitinase 7.8 +/- 0.20
at 144 h incubation and beta-N-acetylhexosaminidase 38.3 +/- 02 at 120 h
incubation in CWB medium. Production of extracellular chitin deacetylase by P.
monoverticillium CFR 2 and F. oxysporum CFR 8 in SSF is being reported for the
first time.
PMID- 25114355
TI - Combined effect of ohmic heating and enzyme assisted aqueous extraction process
on soy oil recovery.
AB - This research describes a new technological process for soybean oil extraction.
The process deals with the combined effect of ohmic heating and enzyme assisted
aqueous oil extraction process (EAEP) on enhancement of oil recovery from soybean
seed. The experimental process consisted of following basic steps, namely,
dehulling, wet grinding, enzymatic treatment, ohmic heating, aqueous extraction
and centrifugation. The effect of ohmic heating parameters namely electric field
strength (EFS), end point temperature (EPT) and holding time (HT) on aqueous oil
extraction process were investigated. Three levels of electric field strength
(i.e. OH600V, OH750V and OH900V), 3 levels of end point temperature (i.e. 70, 80
and 90 degrees C) and 3 levels of holding time (i.e. 0, 5 and 10 min.) were
taken as independent variables using full factorial design. Percentage oil
recovery from soybean by EAEP alone and EAEP coupled with ohmic heating were
53.12 % and 56.86 % to 73 % respectively. The maximum oil recovery (73 %) was
obtained when the sample was heated and maintained at 90 degrees C using
electric field strength of OH600V for a holding time of 10 min. The free fatty
acid (FFA) of the extracted oil (i.e. in range of 0.97 to 1.29 %) was within the
acceptable limit of 3 % (oleic acid) and 0.5-3 % prescribed respectively by PFA
and BIS.
PMID- 25114354
TI - Optimization of enzymatic hydrolysis of guar gum using response surface
methodology.
AB - Guar gum is a polysaccharide obtained from guar seed endosperm portion.
Enzymatically hydrolyzed guar gum is low in viscosity and has several health
benefits as dietary fiber. In this study, response surface methodology was used
to determine the optimum conditions for hydrolysis that give minimum viscosity of
guar gum. Central composite was employed to investigate the effects of pH (3-7),
temperature (20-60 degrees C), reaction time (1-5 h) and cellulase concentration
(0.25-1.25 mg/g) on viscosity during enzymatic hydrolysis of guar (Cyamopsis
tetragonolobus) gum. A second order polynomial model was developed for viscosity
using regression analysis. Results revealed statistical significance of model as
evidenced from high value of coefficient of determination (R(2) = 0.9472) and P <
0.05. Viscosity was primarily affected by cellulase concentration, pH and
hydrolysis time. Maximum viscosity reduction was obtained when pH, temperature,
hydrolysis time and cellulase concentration were 6, 50 degrees C, 4 h and 1.00
mg/g, respectively. The study is important in optimizing the enzymatic process
for hydrolysis of guar gum as potential source of soluble dietary fiber for human
health benefits.
PMID- 25114356
TI - Effect of partial replacement of sugar with stevia on the quality of kulfi.
AB - Stevia is a natural sweetener obtained from the leaf of Stevia rebaudiana plant.
Its refined extract powder is 130-300 times sweeter than sucrose. Besides, it
prevents diabetes, decreases weight, prevents tooth decay, increases digestion
etc. Dietetic kulfi was produced, in which 50, 60 and 70% sugar was replaced with
0.05, 0.06 and 0.07% refined stevia extract powder respectively. At higher levels
of sugar replacement there was a significant decrease in specific gravity,
melting rate, carbohydrate percentage and total calorie content and a significant
increase in freezing point, hardness and fat, protein, ash and moisture
percentage. Kulfi prepared by replacing half the sugar content with stevia was
adjudged on par with the control in sensory characteristics. Above 50% sugar
replacement resulted in bitterness, lack of brownish appearance and presence of
icy texture.
PMID- 25114358
TI - Development of post-harvest protocol of okra for export marketing.
AB - The study was carried out on the harvesting and handling methods of okra with the
objective to maintain the best quality of pods from harvesting to end consumer
especially for export marketing. For that purpose okra cv. 'Punjab-8' pods were
harvested with minimum handling (least injuries to the pubescence on the ridges
of pod) and normal handling (no safety taken to prevent injuries on pods). Pods
were precooled at 15 +/- 1oC, 90-95% RH; jumble packed in the CFB boxes of 2.0 Kg
capacity and than stored at 8 +/- 1oC, 90-95% RH. The quality parameters of okra
namely texture, chlorophyll content, physiological loss in weight, rotting
percentage and general appearance were studied. The pods harvested with minimum
handling and field packaging can retain their green colour, crisp texture
(maximum force to puncture pod = 500.2 g) with minimum rotting (3.0%) and
physiological loss in weight (15.8%) and good appearance upto 13 days of cold
storage whereas normal handled pods can be stored upto 5 days at 8 +/- 1oC, 90
95% RH and thereafter lost their general appearance on the 7th day of storage and
were discarded. Therefore, in order to maintain high quality of okra from
harvesting to the final destination (consumer), the okra pods should be harvested
with minimum handling followed by field packaging in CFB boxes.
PMID- 25114357
TI - Minerals and antinutrients profile of rabadi after different traditional
preparation methods.
AB - Rabadi is a cereal and buttermilk based traditional fermented recipe of western
region of India. There are many traditional preparation methods, which may alter
biochemical composition of rabadi, therefore, in the present study, role of
traditional processings (cooking, fermentation, dehulling, utensil, preparation
methods and cereals) on minerals and antinutrients of pearl millet, wheat flour
and refined wheat flour rabadi was investigated on fresh weight basis. Results
showed that the process of cooking and fermentation enhanced minerals (Ca, Fe and
P) in all types of rabadi samples at different levels of significance, while
antinutrients (phytic acid, total phenols and oxalates) reflected a declining
trend. Intercomparison of different types of rabadies exhibited that fermented-
cooked -fermented samples were better than cooked -fermented rabadies. Dehulling
caused a loss of minerals, but antinutrients were also degraded after dehulling;
therefore dehulled sample showed very good nutritional profile after
fermentation. Earthen pot rabadi samples presented better biochemical composition
than rabadies prepared in steel pot. Intercomparison of different cereals based
rabadies reflected superior position of fermented -cooked- fermented pearl millet
flour rabadi than cooked- fermented pearl millet flour rabadi, wheat and refined
wheat flour rabadi samples.
PMID- 25114359
TI - Antioxidant and antiplatlet aggregation properties of bark extracts of Garcinia
pedunculata and Garcinia cowa.
AB - The bark extracts of Garcinia pedunculata and Garcinia cowa, which are abundant
in the Northeastern regions of India, were screened for their antioxidant and in
vitro antiplatelet aggregating activities. By beta-carotene linoleate model for
antioxidant assay, acetone extract of G. pedunculata and hexane extracts of G.
cowa exhibited higher antioxidant activity (86.47 and 66.94 % respectively, at 25
ppm) than other extracts. Similar pattern was observed for superoxide radical
scavenging method for antioxidant assay. The ethyl acetate extract of G.
pedunculata and hexane extract of G. cowa exhibited higher antiplatelet
aggregation capacity towards ADP induced platelet aggregation (IC50 0.16 and 0.43
ug, respectively) than other extracts.
PMID- 25114360
TI - Hepatitis A virus in West Africa: Is an epidemiological transition beginning?
AB - BACKGROUND: Studies of hepatitis A virus (HAV) seroprevalence in sub-Saharan
Africa have generally found very high anti-HAV IgG seroprevalence rates, but
economic development and improved drinking water access may be contributing to
decreasing incidence. MATERIALS AND METHODS: This review evaluates all 19
articles that have been published on HAV epidemiology in West Africa. RESULTS:
Nearly all studies conducted before 1990 found that the majority of preschool
aged children had already developed immunity due to prior infection. However,
several recent studies have observed that the age at midpoint of population
immunity in some urban populations has shifted to school-aged children.
CONCLUSION: There is preliminary evidence that some West-African countries are
beginning the transition towards lower hepatitis A endemicity levels. Additional
studies of child seroprevalence rates in diverse parts of West Africa are
required in order to clarify the extent to which an early transition may be
occurring.
PMID- 25114361
TI - Comparison of values of traditionally measured venous bicarbonate with calculated
arterial bicarbonate in intensive care unit patients of a hospital in a third
world country.
AB - BACKGROUND: Measurement of serum or plasma bicarbonate (HCO3 (-)) from a sample
of peripheral venous blood is routinely practiced in hospital patient
managements. HCO3 (-) status can also be obtained by a simple calculation during
blood gas analysis requiring arterial blood as sample which is cumbersome for
both patient and doctor. This study compared the measured bicarbonate levels with
calculated arterial values in intensive care unit (ICU) patients to determine
whether traditionally measured venous HCO3 (-) and calculated HCO3 (-) values
[from arterial blood gas (ABG) analyzers] can be used interchangeably. MATERIALS
AND METHODS: This prospective study was carried out at a tertiary care teaching
hospital in Dhaka, the capital of Bangladesh. A total of 56 adult patients with
diverse medical conditions, presenting at the ICU of the health centre were
enrolled in this study when deemed by the treating physician to have an ABG
analysis. Arterial and venous samples were taken as close in time as possible for
gas analysis and routine blood tests. RESULTS: The HCO3 (-) levels from ABG and
traditionally measured serum showed acceptably narrow 95% limits of agreement
using the Bland-Altman method. CONCLUSIONS: More widely prescribed venous HCO3 (
) measurements can also be a useful substitute for an expensive ABG analyzer in
resource-constrained health care sectors when required. However, accuracy of
venous blood in assessment of additional ABG parameters is yet to be discovered.
PMID- 25114362
TI - Is total lymphocyte count a predictor for CD4 cell count in initiation
antiretroviral therapy in HIV-infected patients?
AB - BACKGROUND: Since laboratory assessments of HIV-infected patients by flow
cytometric methods are expensive and unavailable in resource-limited countries,
total lymphocyte count by haematology cell counter is supposed to be a suitable
surrogate marker to initiate and monitor course of the disease in these patients.
The aim of this study was to evaluate the utility of total lymphocyte count as a
surrogate marker for CD4 count in HIV-infected patients. PATIENTS AND METHODS: In
a prospective study 560 HIV-positive individuals evaluated for total and CD4
lymphocyte count. For correlation between CD4 count and total lymphocyte count,
haemoglobin and haematocrit we defined cut-off values as 200 cell/MUl, 1200
cell/MUl, 12 gr/dl and 30%, respectively, and compared CD4 count with each
parameter separately. Positive predictive value, negative predictive value,
sensitivity and specificity of varying total lymphocyte count cutoffs were
computed for CD4 count <= 200 cell/MUl and <= 350 cell/MUl. RESULTS: Strong
degree of correlation was noted between CD4 and total lymphocyte count (r: 0.610,
P < 0.001). Mean and standard deviation of total lymphocyte count, haemoglobin
and haematocrit in relation to CD4 count were calculated which indicated
significant correlation between these variables. Kappa coefficient for agreement
was also calculated which showed fair correlation between CD4 200 cell/MUl and
total lymphocyte count 1200 cell/MUl (0.35). CONCLUSION: This study reveals that
despite low sensitivity and specificity of total lymphocyte count as a surrogate
marker for CD4, total lymphocyte count is of great importance and benefit in
resource-limited settings.
PMID- 25114363
TI - Acceptability of HIV/AIDS testing among pre-marital couples in Iran (2012).
AB - BACKGROUND: Human immunodeficiency virus (HIV)/acquired immune deficiency
syndrome (AIDS) is a lifestyle-related disease. This disease is transmitted
through unprotected sex, contaminated needles, infected blood transfusion and
from mother to child during pregnancy and delivery. Prevention of infection with
HIV, mainly through safe sex and needle exchange programmes is a solution to
prevent the spread of the disease. Knowledge about HIV state helps to prevent and
subsequently reduce the harm to the later generation. The purpose of this study
was to assess the willingness rate of couples referred to the family regulation
pre-marital counselling centre for performing HIV test before marriage in Yazd.
PATIENTS AND METHODS: In this descriptive study, a simple random sampling was
done among people referred to Akbari clinic. The couples were 1000 men and 1000
women referred to the premarital counselling centre for pre-marital HIV testing
in Yazd in the year 2012. They were in situations of pregnancy, delivery or
nursing and milking. The data were analyzed using Statistical Package for the
Social Sciences (SPSS) software and chi-square statistical test. RESULTS: There
was a significant statistical difference between the age groups about willingness
for HIV testing before marriage (P < 0.001) and also positive comments about HIV
testing in asymptomatic individuals (P < 0.001). This study also proved a
significant statistical difference between the two gender groups about
willingness to marry after HIV positive test of their wives. CONCLUSION: The
willingness rate of couples to undergo HIV testing before marriage was
significant. Therefore, HIV testing before marriage as a routine test was
suggested.
PMID- 25114364
TI - Nodal vascularity as an indicator of cervicofacial metastasis in oral cancer: A
Doppler sonographic study.
AB - BACKGROUND: The objective of this study was to assess nodal vascularity by
Doppler sonography and to find out the correlation between clinical and various
Doppler sonographic features for the detection of the metastatic nodes in oral
cancer patients. PATIENTS AND METHODS: A total number of 55 patients of
histopathologically proven oral cancer presenting with enlarged superficial
cervicofacial lymph nodes were included in the study. Patients were subjected to
clinical examination according to a specially designed proforma and the TNM
staging was done. If more than one enlarged nodes were present, then the node
with the largest diameter was chosen for further Doppler ultrasonographic
examination followed by fine needle aspiration cytology test of the same node.
RESULTS: Correlations of patterns of color Doppler flow signals with cytological
diagnosis showed that central type of vascular pattern was statistically
significant parameter for benign lymph nodes and peripheral type of vascularity
was highly significant parameter for malignant lymphadenopathy. It was found that
the cut-off value of resistive index 0.6 was statistically significant in the
assessment of metastatic node (P < 0.01) with a sensitivity of 45.5% and
specificity of 93.9%. On comparison of the clinical features (TNM staging) with
Doppler sonographic features, it was found that the characteristic features
suggestive of malignant lymph nodes on Doppler sonography such as peripheral
blood flow and high resistive index were more consistently and frequently
associated with the higher sub-stages of T3 and T4 and N2b and N2c of TNM staging
system. CONCLUSION: Nodal vascularity may be used to differentiate benign from
malignant lymphadenopathy. Proper judicious use of non-invasive color Doppler
ultrasonographic examination provides an opportunity to eliminate the need for
biopsy in reactive nodes and provide treatment in a more precise manner.
PMID- 25114365
TI - Respiratory symptom, lung function and exhaled carbon monoxide among a sample of
traffic workers in Lagos, Nigeria: A pilot survey.
AB - BACKGROUND: Traffic-related air pollution (TRAP) is a major source of air
pollution but the impact on health in Nigeria is not well described. PATIENTS AND
METHODS: A descriptive cross-sectional study of road traffic workers and
university students in Lagos. Eligible, accessible and willing participants were
included in the sample. Respiratory symptoms and anthropometry were obtained from
all the participants using an adapted Medical Research Council (MRC)
questionnaire and they all did a spirometry test and exhaled carbon monoxide (CO)
test. RESULTS: Fifty-nine individuals participated with complete data, including
47 traffic policemen and 12 students who acted as controls. The mean age (SD) was
35.1 (8.0) and 35.4 years (6.3) for the traffic workers and students,
respectively. All the respondents were men. The mean (SD) duration of occupation
as a traffic policeman was 4.4 (4.4) and a median of 4 years (range 1-25). There
was no significant difference in the presentation of respiratory and non
respiratory symptoms between the two groups. Compared with the students, the
traffic workers had higher age, height and sex adjusted forced expiratory volume
in one second and forced vital capacity. Traffic policemen had significantly
higher levels of exhaled CO than the students (1.18 vs 0.73 ppm, P < 0.006).
CONCLUSION: There is a high prevalence of respiratory symptoms in both traffic
policemen and non-traffic residents of Lagos metropolis, indicating widespread
pollution.
PMID- 25114366
TI - Objective structured clinical examination vs traditional clinical examination: An
evaluation of students' perception and preference in a Nigerian medical school.
AB - BACKGROUND: Method of testing clinical competence of medical students in this
setting has been controversial. This report evaluates the perceptions and
preferences of 5(th) and 6(th) year medical students about traditional clinical
examination (TCE) and objective structured clinical examination (OSCE). MATERIALS
AND METHODS: A cross-sectional study using a structured questionnaire,
administered to 156 students, who had been previously exposed to TCE and OSCE.
RESULTS: There were 110 (70.5%) males and 46 (29.5%) females, with median age
group of 26-30 years. One hundred and thirty-one respondents (84%) felt TCE is
more difficult and 20 (12.8%) felt OSCE was more difficult. One hundred and forty
two (91%) felt OSCE was easier to pass, 8 (5.1%) felt TCE was easier to pass and
6 (3.8%) were undecided. Majority of the 5(th) and 6(th) year students (95.5% and
100%, respectively) preferred OSCE for assessment. In relation to validity and
reliability of OSCE, 124 (79.5%) of all the students felt it provides a true
measure of essential clinical skills, 130 (83.3%) felt its scores are
standardised, 143 (91.7%) felt it is a practical and useful experience and 135
(86.5%) felt students' personality, ethnicity and gender will not affect OSCE
scores. Overall, there were no significant differences in preference and
perceptions between 5(th) and 6(th) year students and between males and females.
CONCLUSION: Students preferred OSCE as method of assessing clinical competence
and considered it a more valid and reliable method of examination.
PMID- 25114367
TI - Age-predicted vs. measured maximal heart rate in young team sport athletes.
AB - BACKGROUND: Although maximal heart rate (HR)max is used widely to assess exercise
intensity in sport training and particularly in various team sports, there are
limited data with regards to the use of age-based prediction equations of HRmax
in sport populations. The aim of this study was to compare the measured-HRmax
with three prediction equations (Fox-HRmax = 220-age and Tanaka-HRmax = 208
0.7*age and Nikolaidis-HRmax = 223-1.44*age) in young team sport athletes.
MATERIALS AND METHODS: Athletes of soccer, futsal, basketball and water polo,
classified into three age groups (u-12, 9-12 years, n = 50; u-15, 12-15 years, n
= 40; u-18, 15-18 years, n = 57), all members of competitive clubs, voluntarily
performed a graded exercise field test (20 m shuttle run endurance test) to
assess HRmax. RESULTS: Fox-HRmax and Nikolaidis-HRmax overestimated measured
HRmax, while Tanaka-HRmax underestimated it (P < 0.001). However, this trend was
not consistent when examining each group separately; measured-HRmax was similar
with Tanaka-HRmax in u-12 and u-15, while it was similar with Nikolaidis-HRmax in
u-18. CONCLUSION: The results of this study failed to validate two widely used
and one recently developed prediction equations in a large sample of young
athletes, indicating the need for specific equation in different age groups.
Therefore, coaches and fitness trainers should prefer Tanaka-HRmax when desiring
to avoid overtraining, while Fox-HRmax and Nikolaidis-HRmax should be their
choice in order to ensure adequate exercise intensity.
PMID- 25114368
TI - The diagnostic value of cervicovaginal and serum ferritin levels in midgestation
time to predict spontaneous preterm delivery.
AB - BACKGROUND: The aim of this study was to determine diagnostic value of
cervicovaginal ferretin and serum ferretin levels at midgestation time in
predicting preterm delivery in singleton pregnancies. PATIENTS AND METHODS: A
diagnostic test study through a prospective cohort design was carried out on 300
singleton pregnant women in 2012. A blood sample was obtained from all the
patients within 22-24 gestational weeks for laboratory assessment of serum
ferretin, and cervicovaginal sample was also taken to assess cervicovaginal
ferritin level. Ferritin levels were compared between term and preterm deliveries
at 37, 34 and 32 weeks of gestation. Receiver operating characteristics (ROC)
curves were plotted to assess the diagnostic test values. RESULTS: Mean serum
ferritin level was 55.38 [standard deviation (SD 23.8)] ng/mL in term deliveries
versus a mean of 91.27 (SD 25.2) ng/mL in preterm deliveries, which showed a
statistically significant difference (P < 0.001). The ferritin levels in
cervicovaginal term delivery group had mean of 11.29 (SD 16.2) ng/mL compared
with a mean of 21.95 (SD 10.1) ng/mL among those with preterm delivery before 37
weeks of gestational age(P < 0.001). The cervicovaginal ferritin level had a
moderate to good diagnostic value with an area under curve being above 0.8 for
all assessments. The serum ferritin level had a moderate to good diagnostic value
with an area under curve being above 0.8 for all assessments. In both tests, its
diagnostic value was higher for predicting preterm delivery at earlier
gestational age. CONCLUSIONS: The results of this study indicate that high levels
of serum and cervicovaginal ferritin in singleton pregnancies may alert the
clinician of the risk of preterm delivery. Serum and cervicovaginal ferritin
measurement at midgestation may be used as a predictive scale for preterm
delivery in singleton pregnancies.
PMID- 25114369
TI - Risk factors and drug-resistance patterns among pulmonary tuberculosis patients
in northern Karnataka region, India.
AB - BACKGROUND: India is one of the high tuberculosis (TB)-burden countries in the
world. Resistance to anti-tuberculosis (anti-TB) drugs has already become an
important and alarming threat in most of the regions worldwide. India ranks
second in the world in harbouring multi-drug resistant cases (MDRTB). Prevalence
of MDR-TB mirrors the functional state and efficacy of TB control programmes and
realistic attitude of the community towards implementation of such programmes.
The most important risk factor in the development of MDRTB is improper
implementation in the guidelines in the management of TB, and high rate of
defaults on the part of the patients. The study was carried out to evaluate the
drug resistance pattern to first line anti-TB drugs in Northern Karnataka region,
India. MATERIALS AND METHODS: A prospective study was conducted at J. N. Medical
College and its associated Hospitals, Belgaum. Between January 2011 and December
2012, 150 sputum samples of suspected pulmonary TB patients based on the history
were examined for the AFB culture by Lowenstein-Jensen (LJ) culture technique. A
total of two early morning samples were collected for the smear [Ziehl-Neelsen
(ZN) staining] and culture methods. It was observed that ZN staining for AFB was
positive in 113 patients (75%), while AFB culture by LJ medium yielded growth in
66 cases (44%). Thus, a total of 66 AFB culture-positive samples by LJ medium
were subjected for AFB drug-sensitivity testing (DST). DST was done for Isoniazid
(INH), Rifampicin (RIF), Pyrazinamide (PZA), Ethambutol (EMB) and Streptomycin
(SM) after isolation by using the resistance proportion method. RESULTS: A total
of 66 AFB culture-positive specimens, 20 (30.3%) cases were sensitive to all the
five drugs while 46 (69.7%) cases showed resistance to one or more drugs. Among
these, the resistance to rifampicin was highest (80.4%), while resistance to
isoniazid, pyrazinamide, ethambutol and streptomycin were observed to be 60%,
58.7%, 52.1% and 63%, respectively. It was also observed that, resistance to all
five drugs was highest (39.18%). MDR isolates were obtained in 52.2% of the
cases. Illiteracy, low socio-economic status, previous history of TB and
alcoholism were found to have statistically significant association for the
development of MDR. CONCLUSIONS: The prevalence of drug resistance in the present
study was observed to be 69.7%. More than half of the cases were multi-drug
resistant. The most common resistant pattern observed in this study was
resistance to all the first-line drugs. Therefore, during initiation of new case
proper explaining and completion of the treatment is very important to avoid the
development of future drug resistance in the society.
PMID- 25114370
TI - Early outcome of incisional hernia repair using polypropylene mesh: A preliminary
report.
AB - BACKGROUND: The use of prosthetics for open repair of incisional hernia is very
recent in our practice. We highlight our experience repairing incisional hernias
with polypropylene mesh. PATIENTS AND METHODS: Patients presenting with
incisional hernia >5 cm in length or width received open polypropylene mesh
repair and were followed for two years. Data obtained included age, sex, primary
surgery causing the hernia, the length of the fascial defect and previous
attempts at repair. Post-operative wound complications were recorded. The
integrity of the scar and patient satisfaction or concerns with the repair was
assessed at each visit. RESULTS: Nineteen females with a mean age of 35 years
(range 30-54) underwent repair; most arising from obstetric or gynaecological
procedures. Sixteen (82.2%) had midline, 2 (10.5) transverse and 1 (5.3)
Pfannenstiel scars. One patient had no previous repair (R0), 7 had undergone one
repair (R1), 9 had undergone two repairs (R2) and 1 had three previous repairs
(R3). The length of fascial defects ranged from 8 to 18 cm and seroma collection
and stitch sinus were the common problems encountered. Two (10.5%) recurrences
were recorded in two years. CONCLUSION: Open mesh repair of incisional hernia
carries a low risk of infection and recurrence in two years.
PMID- 25114371
TI - Accuracy of subjective assessment of fever by Nigerian mothers in under-5
children.
AB - BACKGROUND: Many mothers still rely on palpation to determine if their children
have fever at home before deciding to seek medical attention or administer self
medications. This study was carried out to determine the accuracy of subjective
assessment of fever by Nigerian mothers in Under-5 Children. PATIENTS AND
METHODS: Each eligible child had a tactile assessment of fever by the mother
after which the axillary temperature was measured. Statistical analysis was done
using SPSS version 19 (IBM Inc. Chicago Illinois, USA, 2010). RESULT: A total of
113 mother/child pairs participated in the study. Palpation overestimates fever
by 24.6%. Irrespective of the surface of the hand used for palpation, the
sensitivity, specificity, positive predictive value (PPV) and negative predictive
value (NPV) of tactile assessment were 82.4%, 37.1%, 51.9% and 71.9%,
respectively. The use of the palmer surface of the hand had a better sensitivity
(95.2%) than the dorsum of the hand (69.2%). The use of multiple sites had better
sensitivity (86.7%) than the use of single site (76.2%). CONCLUSION: Tactile
assessment of childhood fevers by mothers is still a relevant screening tool for
the presence or absence fever. Palpation with the palmer surface of the hand
using multiple sites improves the reliability of tactile assessment of fever.
PMID- 25114372
TI - Post-graduate surgical training in Nigeria: The trainees' perspective.
AB - BACKGROUND: Quality surgical training is crucial to meeting manpower needs and
creating a vibrant healthcare delivery. Feedback from trainees provides insight
to understanding training challenges and needs to improve the programme. The
objective of this study was to determine the challenges faced by surgical
trainees and their perception of their training in Nigeria. MATERIALS AND
METHODS: A questionnaire survey of trainees in 16 academic surgical training
centres in Nigeria between September and December 2012. RESULTS: Of 235
respondents, 227 were males (96.6%) and 8 females (3.4%) with mean age of 33.9
years. A significant proportion (62.3%) of the respondents believed that the
volume and diversities of surgical cases managed during their training were
sufficient; however, 53.9% were less satisfied with their operative experience.
Majority (71.8%) of the respondents felt "supported" by their trainers but they
also believed that the training was skewed towards service provision. They were
not actively involved in research due to lack of funds in 77.7%, lack of
time/motivation in 15.8%, indifference in 11.8% and poor knowledge of research
methods in 9.2%. Inadequate training facilities (50.7%), poor welfare (67.2%),
inadequate sponsorship (65.9%) and poor remuneration (88.3%) were identified
among their challenges. On the whole, majority (62.3%) believed that their
training would adequately prepare them to function independently. CONCLUSION:
Surgical residents in Nigeria face a variety of challenges. Based on our
findings, a training that tracks and keeps trend with global changes through a
higher investment in surgical training, improved facilities and residents' well
being from both the teaching authorities and government will more likely improve
the quality of training.
PMID- 25114373
TI - Comparison effect of intravenous tranexamic acid and misoprostol for postpartum
haemorrhage.
AB - BACKGROUND: Postpartum haemorrhage (PPH) is the third-most common cause of
maternal death in the United States and it is still the first prevalent cause of
maternal death in developing countries. Active prevention of haemorrhage with an
uterotonic or other new drugs leads to a decrease in postpartum vaginal
haemorrhage. The aim of this study was to compare anti-haemorrhagic effect of
Tranexamic acid (TXA) and Misoprostol for PPH. PATIENTS AND METHODS: In a double
blinded randomised control clinical trial, 200 women were included after
Caesarean or natural vaginal delivery with abnormal PPH. They were divided into
two equal intervention and control groups. Effect of intravenous TXA and
Misoprostol for postpartum haemorrhage was examined. RESULTS: The mean age of
patients was 26.7 +/- 6.5 years which ranged from 14 to 43 years. The sonographic
gestational age in the group treated with TXA was 37.7 +/- 3.4 weeks and it was
37.4 +/- 3.3 weeks for the other group (P = 0.44). The haemorrhage in the TXA and
Misoprostol groups was 1.2 +/- 0.33 litres and 1.18 +/- 0.47 litres, respectively
(P = 0.79). The haemoglobin levels after 6-12 hours of labour, in TXA group was
more than that of the Misoprostol group, but this difference was not
statistically significant (P = 0.22 and P = 0.21, respectively). CONCLUSION:
Regarding to the superior results in Misoprostol group in one hand and lack of
significant differences between two groups in haemorrhage during labour, post
partum haemoglobin level and discharge haemoglobin level, we can state that
Misoprostol has no specific preferences to TXA, but more studies with greater
population are needed.
PMID- 25114374
TI - Cardiac left ventricular thrombus in protein C deficiency.
AB - We report an exceptional case of, 33-year-old woman presenting with, dyspnoea and
chest pain, Cardio respiratory sign and symptom related to diastolic dysfunction
caused by mass effect of thrombosis on diastolic filling of left ventricule (LV).
The common aetiologies of these devastating complication results in
thrombophillia diagnosis, and echocardioghraphy showed a large mass in left
ventricular cavity. In laboratory exam, protein C-S deficiency was confirmed
however, others related test of thrombophillia were negative. The patient
underwent cardiopulmonary bypass with thrombosis extraction and her sign and
symptom, recovered uneventfully. This case report illustrates an exceedingly rare
case of thrombophilia-induced left ventricular clot formation.
PMID- 25114375
TI - Coronary artery spasm: An often overlooked diagnosis.
AB - Coronary vasospasm can lead to myocardial injury and even sudden cardiac death.
It has generally been overlooked as a diagnosis since atherosclerosis is a more
common cause of acute coronary syndromes and because of the dilemma involved in
its diagnosis. A middle-aged man with a history of smoking and cocaine use
presented to the emergency department with left-sided arm/chest discomfort and
diaphoresis. The electrocardiogram showed anterior ST elevation and hyper-acute T
waves, which completely resolved shortly after sublingual nitroglycerin was
administered. Subsequent angiogram revealed a 70% focal stenosis in the mid-left
anterior descending artery. Coronary vasospasm occurs more commonly in arteries
with underlying atheromatous disease, although normal vessels are not excluded.
Cigarette smoking and cocaine use are among the major culprits that have been
implicated as risk factors for the occurrence of coronary vasospasm. Eventually,
the patient had percutaneous coronary intervention of his left-anterior
descending artery and remained asymptomatic.
PMID- 25114376
TI - See-saw pattern in ventilator graphic: Is there any story behind?
AB - The importance of ventilator graphics cannot be over emphasized that provide the
useful information about airway, ventilation, compliance and lung mechanics. Some
bizarre forms of graphics are usually overlooked in view of artifacts, but
sometimes these tracings may in fact predict some relevant information.
PMID- 25114377
TI - Study of the correlations among some parameters of the oxidative status,
gelatinases, and their inhibitors in a group of subjects with metabolic syndrome.
AB - Our aim was to examine some parameters of oxidative status, gelatinases, and
their inhibitors and to evaluate their interrelationships in subjects with
metabolic syndrome (MS). We enrolled 65 MS subjects, subdivided according to the
presence or not of diabetes mellitus. We examined lipid peroxidation (expressed
as thiobarbituric acid reacting substances, TBARS), protein oxidation (expressed
as carbonyl groups), nitric oxide metabolites (NO x ), total antioxidant status
(TAS), MMP-2, MMP-9, TIMP-1, and TIMP-2. We found that MS subjects, diabetics and
nondiabetics, showed an increase in TBARS, PC, and NO x . A significant decrease
in TAS was observed only in nondiabetic MS subjects in comparison with diabetic
MS subjects. We observed increased concentrations of MMP-2, MMP-9, TIMP-1, and
TIMP-2, higher in diabetic subjects. Our data showed a positive correlation
between TAS and MMP-2, TAS and MMP-9, and TAS and MMP-9/TIMP-1 and a negative
correlation between TBARS and MMP-2 in diabetic MS subjects in the entire group.
In MS subjects a prooxidant status and increased levels of gelatinases and their
inhibitors are evident although the correlations between oxidative stress and
MMPs or TIMPs are controversial and need further investigation.
PMID- 25114378
TI - Overexpression and selectively regulatory roles of IL-23/IL-17 axis in the
lesions of oral lichen planus.
AB - Interleukin- (IL-) 23/IL-17 axis is a newly discovered proinflammatory signaling
pathway and has been implicated in the pathogenesis of many chronic inflammatory
and immune disorders. Here we investigated whether the IL-23/IL-17 axis was
present and functional in the lesions of oral lichen planus (OLP), a chronic
inflammatory disease affecting the oral mucosa. Using immunohistochemistry and
quantitative PCR, we found that the subunits of IL-23 and IL-17 were
overexpressed in OLP lesions than in normal oral mucosa tissues. In addition, the
expressions of IL-23 and IL-17 are positively correlated in reticular OLP
tissues. Results from in vitro studies revealed that exogenous IL-23 could
increase the percentage of Th17 cells and IL-17 production in the CD4+T cells
from reticular OLP patients. Furthermore, we also found that exogenous IL-17
could significantly enhance the mRNA expressions of beta-defensin-2, -3, CCL-20,
IL-8, and TNF-alpha, but not beta-defensin-1, CXCL-9, -10, -11, CCL-5, and IL-6
in human oral keratinocytes. Taken together, our results revealed an
overexpression pattern and selectively regulatory roles of IL-23/IL-17 axis in
the OLP lesions, suggesting that it may be a pivotal regulatory pathway in the
complex immune network of OLP lesions.
PMID- 25114382
TI - Guest editorial.
PMID- 25114381
TI - Pursuing a radiology career: Private practice or academic ?
PMID- 25114379
TI - Overexpression of receptor for advanced glycation end products and high-mobility
group box 1 in human dental pulp inflammation.
AB - High mobility group box 1 (HMGB1), a nonhistone DNA-binding protein, is released
into the extracellular space and promotes inflammation. HMGB1 binds to related
cell signaling transduction receptors, including receptor for advanced glycation
end products (RAGE), which actively participate in vascular and inflammatory
diseases. The aim of this study was to examine whether RAGE and HMGB1 are
involved in the pathogenesis of pulpitis and investigate the effect of Prevotella
intermedia (P. intermedia) lipopolysaccharide (LPS) on RAGE and HMGB1 expression
in odontoblast-like cells (OLC-1). RAGE and HMGB1 expression levels in clinically
inflamed dental pulp were higher than those in healthy dental pulp. Upregulated
expression of RAGE was observed in odontoblasts, stromal pulp fibroblasts-like
cells, and endothelial-like cell lining human pulpitis tissue. Strong cytoplasmic
HMGB1 immunoreactivity was noted in odontoblasts, whereas nuclear HMGB1
immunoreactivity was seen in stromal pulp fibroblasts-like cells in human
pulpitis tissue. LPS stimulated OLC-1 cells produced HMGB1 in a dose-dependent
manner through RAGE. HMGB1 translocation towards the cytoplasm and secretion from
OLC-1 in response to LPS was inhibited by TPCA-1, an inhibitor of NF-kappaB
activation. These findings suggest that RAGE and HMGB1 play an important role in
the pulpal immune response to oral bacterial infection.
PMID- 25114380
TI - Impaired resolution of inflammation in the Endoglin heterozygous mouse model of
chronic colitis.
AB - Endoglin is a coreceptor of the TGF-beta superfamily predominantly expressed on
the vascular endothelium and selective subsets of immune cells. We previously
demonstrated that Endoglin heterozygous (Eng (+/-)) mice subjected to dextran
sulfate sodium (DSS) developed persistent gut inflammation and pathological
angiogenesis. We now report that colitic Eng (+/-) mice have low colonic levels
of active TGF-beta1, which was associated with reduced expression of
thrombospondin-1, an angiostatic factor known to activate TGF-beta1. We also
demonstrate dysregulated expression of BMPER and follistatin, which are
extracellular regulators of the TGF-beta superfamily that modulate angiogenesis
and inflammation. Heightened colonic levels of the neutrophil chemoattractant and
proangiogenic factor, CXCL1, were also observed in DSS-treated Eng (+/-) mice.
Interestingly, despite increased macrophage and neutrophil infiltration, a gut
specific reduction in expression of the key phagocytic respiratory burst enzymes,
NADPH oxidase 2 (Nox-2) and myeloperoxidase, was seen in Eng (+/-) mice
undergoing persistent inflammation. Taken together, these findings suggest that
endoglin is required for TGF-beta superfamily mediated resolution of inflammation
and fully functional myeloid cells.
PMID- 25114383
TI - Role of MR spectroscopy in musculoskeletal imaging.
AB - Magnetic resonance spectroscopy (MRS) is an imaging approach that allows for the
noninvasive molecular characterization of a region of interest. By detecting
signals of water, lipids, and other metabolites, MRS can provide metabolic
information for lesion characterization and assessment of treatment response.
Although MRS has been routinely used in the brain, clinical applications within
the musculoskeletal system have only more recently emerged. The aim of this
article is to review the technical considerations for performing MRS in the
musculoskeletal system, focusing on proton MRS, and to discuss its potential
roles in musculoskeletal tumor imaging and the assessment of muscle physiology
and disease.
PMID- 25114384
TI - Peripheral nerve injury grading simplified on MR neurography: As referenced to
Seddon and Sunderland classifications.
AB - The Seddon and Sunderland classifications have been used by physicians for
peripheral nerve injury grading and treatment. While Seddon classification is
simpler to follow and more relevant to electrophysiologists, the Sunderland
grading is more often used by surgeons to decide when and how to intervene. With
increasing availability of high-resolution and high soft-tissue contrast imaging
provided by MR neurography, the surgical treatment can be guided following the
above-described grading systems. The article discusses peripheral nerve anatomy,
pathophysiology of nerve injury, traditional grading systems for classifying the
severity of nerve injury, and the role of MR neurography in this domain, with
respective clinical and surgical correlations, as one follows the anatomic paths
of various nerve injury grading systems.
PMID- 25114385
TI - Bone tumor mimickers: A pictorial essay.
AB - Focal lesions in bone are very common and many of these lesions are not bone
tumors. These bone tumor mimickers can include numerous normal anatomic variants
and non-neoplastic processes. Many of these tumor mimickers can be left alone,
while others can be due to a significant disease process. It is important for the
radiologist and clinician to be aware of these bone tumor mimickers and
understand the characteristic features which allow discrimination between them
and true neoplasms in order to avoid unnecessary additional workup. Knowing which
lesions to leave alone or which ones require workup can prevent misdiagnosis and
reduce patient anxiety.
PMID- 25114386
TI - Imaging of articular cartilage.
AB - We tried to review the role of magnetic resonance imaging (MRI) in understanding
microscopic and morphologic structure of the articular cartilage. The optimal
protocols and available spin-echo sequences in present day practice are reviewed
in context of common pathologies of articular cartilage. The future trends of
articular cartilage imaging have been discussed with their appropriateness. In
diarthrodial joints of the body, articular cartilage is functionally very
important. It is frequently exposed to trauma, degeneration, and repetitive wear
and tear. MRI has played a vital role in evaluation of articular cartilage. With
the availability of advanced repair surgeries for cartilage lesions, there has
been an increased demand for improved cartilage imaging techniques. Recent
advances in imaging strategies for native and postoperative articular cartilage
open up an entirely new approach in management of cartilage-related pathologies.
PMID- 25114388
TI - Role of ultrasound in evaluation of peripheral nerves.
AB - Ultrasonography (USG) is an excellent cost-effective modality in imaging of
peripheral nerves. With the newer high-frequency probes with different footprints
which allow high-resolution imaging at relatively superficial location, USG can
detect and evaluate traumatic, inflammatory, infective, neoplastic, and
compressive pathologies of the peripheral nerves. This article describes the
technique for evaluation of nerves by USG as well as the USG appearances of
normal and diseased peripheral nerves.
PMID- 25114387
TI - Imaging of cartilage repair procedures.
AB - The rationale for cartilage repair is to prevent precocious osteoarthritis in
untreated focal cartilage injuries in the young and middle-aged population. The
gamut of surgical techniques, normal postoperative radiological appearances, and
possible complications have been described. An objective method of recording the
quality of repair tissue is with the magnetic resonance observation of cartilage
repair tissue (MOCART) score. This scoring system evaluates nine parameters that
include the extent of defect filling, border zone integration, signal intensity,
quality of structure and surface, subchondral bone, subchondral lamina, and
records presence or absence of synovitis and adhesions. The five common
techniques of cartilage repair currently offered include bone marrow stimulation
(microfracture or drilling), mosaicplasty, synthetic resorbable scaffold grafts,
osteochondral allograft transplants, and autologous chondrocyte implantation
(ACI). Complications of cartilage repair procedures that may be demonstrated on
magnetic resonance imaging (MRI) include plug loosening, graft protuberance,
graft depression, and collapse in mosaicplasty, graft hypertrophy in ACI, and
immune response leading to graft rejection, which is more common with synthetic
grafts and cadaveric allografts.
PMID- 25114389
TI - Comparison of conventional MRI and MR arthrography in the evaluation wrist
ligament tears: A preliminary experience.
AB - AIMS: To compare conventional magnetic resonance imaging (MRI) and direct
magnetic resonance (MR) arthrography in the evaluation of triangular
fibrocartilage complex (TFCC) and intrinsic wrist ligament tears. MATERIALS AND
METHODS: T1-weighted, fat suppressed (FS) proton density plus T2-weighted (FS
PD/T2), 3D multiple-echo data image combination (MEDIC) sequences and direct MR
arthrography were performed in 53 patients with wrist pain. Images were evaluated
for the presence and location of TFCC, scapholunate ligament (SLL) and
lunatotriquetral ligament (LTL) tears, and imaging findings were compared with
operative findings in 16 patients who underwent arthroscopy or open surgery (gold
standard). RESULTS: SIXTEEN PATIENTS UNDERWENT ARTHROSCOPY/OPEN SURGERY: 12 TFCC
tears were detected arthroscopically out of which 9 were detected on FS PD/T2
sequence, 10 on MEDIC sequence, and all 12 were detected on MR arthrography. The
sensitivities of FS PD/T2, MEDIC sequences, and MR arthrography in the detection
of TFCC tears were 75%, 83.3%, and 100%, respectively. Out of the eight
arthroscopically confirmed SLL tears, three tears were detected on FS PD/T2
sequence, five on MEDIC sequence, and all eight were visualized on MR
arthrography. The sensitivities of FS PD/T2, MEDIC sequences, and MR arthrography
in detecting SLL tears were 37.5%, 62.5%, and 100%, respectively. One
arthroscopically confirmed LTL tear was diagnosed on FS PD/T2 sequence, three on
MEDIC sequence, and all five arthroscopically confirmed LTL tears were detected
with MR arthrography. The sensitivities of PD, MEDIC sequences, and MR
arthrography in detecting LTL tears were 20%, 40%, and 100%, respectively.
CONCLUSIONS: MR arthrography is the most sensitive and specific imaging modality
for the evaluation of wrist ligament tears.
PMID- 25114390
TI - Bilateral congenital absence of flexor pollicis longus with thumb hypoplasia and
thenar atrophy.
AB - Congenital absence of flexor pollicis longus with or without associated anomalies
of thenar muscles and thumb is of rare occurrence. Inability to flex the
interphalangeal joint of the thumb and absent dorsal wrinkles and flexion creases
of the thumb are important clues to the diagnosis. Routine radiography and cross
sectional imaging help to confirm and document the condition. This article
presents an extremely rare case of bilateral congenital absence of flexor
pollicis longus tendon with thumb hypoplasia and thenar atrophy.
PMID- 25114391
TI - Seronegative spondyloarthropathy-related sacroiliitis: CT, MRI features and
differentials.
AB - Seronegative spondyloarthropathy is a group of chronic inflammatory rheumatic
diseases that predominantly affect the axial skeleton. Involvement of sacroiliac
joint is considered a hallmark for diagnosis of seronegative spondyloarthropathy
and is usually the first manifestation of this condition. It is essential for the
radiologist to know the computed tomography (CT) and magnetic resonance imaging
(MRI) features of spondyloarthropathy-related sacroiliitis as imaging plays an
important role in diagnosis and evaluation of response to treatment. We present a
pictorial essay of CT and MRI imaging findings in seronegative
spondyloarthropathy-related sacroiliitis in various stages and highlight common
differentials that need to be considered.
PMID- 25114393
TI - Morel-Lavallee lesion: A closed degloving injury that requires real attention.
AB - Morel-Lavallee lesions are post-traumatic, closed degloving injuries occurring
deep to subcutaneous plane due to disruption of capillaries resulting in an
effusion containing hemolymph and necrotic fat. Magnetic resonance imaging (MRI)
is the modality of choice in the evaluation of Morel-Lavallee lesion. Early
diagnosis and management is essential as any delay in diagnosis or missed lesion
will lead to the effusion becoming infected or leading to extensive skin
necrosis.
PMID- 25114392
TI - Bone marrow lesions: A systematic diagnostic approach.
AB - Bone marrow lesions on magnetic resonance (MR) imaging are common and may be seen
with various pathologies. The authors outline a systematic diagnostic approach
with proposed categorization of various etiologies of bone marrow lesions.
Utilization of typical imaging features on conventional MR imaging techniques and
other problem-solving techniques, such as chemical shift imaging and diffusion
weighted imaging (DWI), to achieve accurate final diagnosis has been highlighted.
PMID- 25114394
TI - MRI imaging of displaced meniscal tears: Report of a case highlighting new
potential pitfalls of the MRI signs.
AB - Magnetic resonance imaging (MRI) has been found to be an excellent imaging tool
for meniscal injuries. Various MRI signs have been described to detect displaced
meniscal injuries, specifically the bucket-handle tears. Although these signs are
quite helpful in diagnosing meniscal tears, various pitfalls have also been
reported for these signs. Double anterior cruciate ligament (ACL) sign refers to
presence of a linear hypointense soft tissue anterior to the ACL, which
represented the flipped bucket-handle tear of the meniscus. Disproportional
posterior horn and flipped meniscus signs represent asymmetrically thickened
horns of the menisci due to overlying displaced meniscal fragments. We report a
case wherein MRI of the knee showed tear and displacement of the medial
patellofemoral ligament (MPFL) and vastus medialis complex, medial collateral
ligament (MCL), and posterior cruciate ligament (PCL) mimicking these signs. To
our knowledge, internally displaced MPFL and MCLs have not been described as
mimics for displaced meniscal fragments.
PMID- 25114395
TI - Antral follicle count in normal (fertility-proven) and infertile Indian women.
AB - BACKGROUND: Antral follicle count (AFC) has been labeled as the most accurate
biomarker to assess female fecundity. Unfortunately, no baseline Indian data
exists, and we continue using surrogate values from the Western literature
(inferred from studies on women, grossly different than Indian women in
morphology and genetic makeup). AIMS: (1) To establish the role of AFC as a
function of ovarian reserve in fertility-proven and in subfertile Indian women.
(2) To establish baseline cut-off AFC values for Indian women. SETTINGS AND
DESIGN: Prospective observational case-control study. MATERIALS AND METHODS:
Thirty patients undergoing workup for infertility were included and compared to
equal number of controls (women with proven fertility). The basal ovarian volume
and AFC were measured by endovaginal. USG the relevant clinical data and hormonal
assays were charted for every patient. STATISTICAL ANALYSIS USED: SPSS platform
was used to perform the Student's t-test and Mann-Whitney U-test for intergroup
comparisons. Correlations were determined by Pearson's ranked correlation
coefficient. RESULTS: Regression analysis revealed the highest correlation of AFC
and age in fertile and infertile patients with difference in mean AFC of both the
groups. Comparison of the data recorded for cases and controls showed no
significant difference in the mean ovarian volume. CONCLUSIONS: AFC has the
closest association with chronological age in normal and infertile Indian women.
The same is lower in infertile women than in matched controls. Baseline and cut
off values in Indian women are lower than that mentioned in the Western
literature.
PMID- 25114396
TI - Transient angioedema of small bowel secondary to intravenous iodinated contrast
medium.
AB - We report the clinical details and imaging findings of a case of transient
angioedema of the small bowel following intravenous administration of non-ionic
iodinated contrast material in a 17 year old female with no predisposing risk
factors. Findings included long segment, symmetric, circumferential, low-density,
bowel wall thickening involving the duodenum, jejunum, and most of the ileum on
computed tomography scan obtained at 7 min following intravenous contrast
material injection. This entity is self-limiting with a favourable clinical
outcome and requires no specific treatment but only aggressive clinical
monitoring.
PMID- 25114397
TI - Imaging in emphysematous epididymo-orchitis: A rare cause of acute scrotum.
AB - Emphysematous epididymo-orchitis is an uncommon, acute inflammatory process of
epididymis and testis characterized by the presence of air within the tissue.
Patient presents with fever, acute pain, swelling and tenderness in the scrotum.
Imaging is needed for rapid accurate diagnosis and to differentiate it from other
causes of acute scrotum such as testicular torsion. We report a case of
emphysematous epididymo-orchitis with imaging findings on plain radiography,
ultrasound, CT and MRI and a brief review of the literature.
PMID- 25114398
TI - Prevalence of bombay group blood in southern bengal population.
PMID- 25114399
TI - Primary hepatic lymphoma: dilemmas in diagnostic approach and therapeutic
management.
AB - Primary hepatic lymphoma (PHL) is a very rare malignancy and is characterized by
liver involvement at presentation with no affectation of the spleen, lymph nodes,
peripheral blood, bone marrow, or other tissues until at least 6 months after
diagnosis. PHL should be considered in the differential diagnosis in a patient
with space-occupying liver lesions and normal levels of alpha-fetoprotein and
CEA. A computed tomography (CT) scan is the commonly used modality for staging
lymphomas. The widespread use of positron emission tomography/CT results in the
improvement in the accuracy of detecting the extent of disease, response
evaluation, and prognostication. The liver biopsy, due to its pleomorphic
appearances in the needle biopsy specimen, can be very challenging. Current
literature favors the combination of chemotherapy as the frontline treatment for
its least invasiveness and improved survival. Favorable prognosis of PHL can be
obtained by early surgery combined with chemotherapy in strictly selected
patients. However, the optimal therapy is still unclear and the outcomes are
uncertain.
PMID- 25114400
TI - Blood substitutes: possibilities with nanotechnology.
AB - Nanotechnology deals with molecules in the nanometer (10(-9)) range and is
currently being used successfully in the field of medicine. Nanotechnology has
important implications in nearly all the branches of medicine and it has all the
capabilities to revolutionize the vast field of medicine in future.
Nanotechnological advancements have been used for the preparation of artificial
hemoglobin. It is formed by assembling the hemoglobin molecules into a soluble
complex. A recent approach includes the assembling of this artificial hemoglobin
with enzymes such as catalase and superoxide dismutase into a nano-complex. This
complex acts as an oxygen carrier as well as an antioxidant in conditions with
ischemia-reperfusion injuries.
PMID- 25114401
TI - Ocular adnexal lymphomas: report of 2 cases of mantle cell lymphomas and short
review of literature.
AB - Mantle cell lymphoma in ocular region is a rare phenomenon which can be either
primary or secondary. Most of these cases are usually diagnosed after excisional
biopsy of the involved area with first visit being in the Ophthalmology OPD. We
share our experience of two such cases being referred from Ophthalmology OPD. 1st
case is about a 52-year-old man who came for complaints of redness of left eye
with excessive lacrimation. Examination revealed congestion of left temporal
bulbar conjunctiva and a small pinkish outgrowth 2 * 2 cm adherent to temporal
bulbar conjunctiva. 2nd case is a 55-year-old gentlemen who presented with
complaints for 8 months duration of swelling left eyelid. Excisional biopsy and
histopathological examination in both the cases were done to confirm the
diagnosis. CECT head and neck were done at baseline and during follow up. These
cases are being presented due to the rarity and dramatic response to
chemotherapy.
PMID- 25114402
TI - Platelet storage media change the expression characteristics of the platelet
derived microparticles.
AB - Activated platelets shed microparticles in vivo and definitely in vitro upon
aging under storage. Studies about the platelet-derived microparticles (PMPs)
produced in different storage media of PC were very limited. The aim of this
research was to compare some surface molecules of these microvesicles in
dissimilar microenvironments; plasma and the candidate medium for the platelet
concentrate, Composol. Thirty units of PCs were prepared from Iranian Blood
Transfusion Organization. Each unit was divided into two portions. In one of the
portions, plasma was replaced with Composol using a connecting device instrument.
MPs were isolated from PC and the levels of PS exposure (the annexin-binding
capacity) and binding to vWF were surveyed on their surface using ELISA and flow
cytometry techniques. The levels of PS exposure were increased on MPs during 7
days storage in the both media but the differences were not significant (P value
>0.05). In addition, binding of PMP to vWF was declined during storage. The
binding capabilities of PMP were significantly higher in Composol than that of
plasma at the day 4 or 7 of storage (P value = 001). It seemed that the binding
of PMPs to vWF was affected from the storage media of PC (plasma and Composol)
but PS exposure was not affected from the type of storage media.
PMID- 25114403
TI - Blood transfusion practice in obstetric and gynecology: impact of educational
programs to create awareness for judicious use of blood components.
AB - The study presents the data analysis (1) To find out the trend of blood component
use during the period 2003-2010 and to determine impact of component awareness
programs on reduction in whole blood (WB) and single unit transfusions. (2) To
determine Hb trigger. The details about blood units issued were entered in the
integrated blood bank management software as well as in Microsoft Excel. The data
of 4,838 cases of pregnancy anemia; 2,244 receiving blood for obstetric (Ob)
hemorrhage including 270 cases of disseminated intravascular coagulation; 1,413
women having Gynecological (Gy) bleeding; 911 Ob, 2,032 Gy and 740 surgeries for
Gy malignancy were analyzed. During the years 2003-2010 there was gradual
increase in component utilization for pregnancy anemia, Ob/Gy surgeries and Ob/Gy
bleeding and significant reduction in WB transfusions due to component awareness
programs. But single unit transfusions showed comparatively lower trend of
reduction. The mean Hb was 6.4 g/dL for pregnancy anemia, 8.1 g/dL for surgeries
and 7.3 g/dL for Ob/Gy bleeding.
PMID- 25114404
TI - Hairy cell leukemia: clinicopathological and immunophenotypic study.
AB - Hairy cell leukemia (HCL) is a rare neoplasm of mature small B lymphoid cells
with characteristic circumferential 'hairy projections' involving the peripheral
blood, bone marrow and splenic red pulp. With the advent of immunophenotyping and
newer treatment modalities, prolonged remission can be achieved after a
definitive diagnosis. Due to the rarity of this condition and presence of only a
few case series from India, this work was undertaken. The aim was to study the
clinico-pathologic and immunophenotypic features of all cases diagnosed as hairy
cell leukemia. The cases were retrieved from Hematopathology records, between
1991 and 2012. The complete clinical details, investigations, treatment and
follow-up were obtained from Medical Oncology records. The peripheral blood
picture, bone marrow cytology and trephine sections along with special stains
were reviewed. There were 12 cases of HCL during the study period with a M:F
ratio of 11:1. Of these, ten were diagnosed as classical HCL and two as variant
HCL. The most common clinical manifestations were fever, easy fatigability and
weakness. Splenomegaly was present in 81.8 % cases. Though all the patients
showed some form of cytopenia, there were three (25 %) patients with
leucocytosis. The smears from all patients showed atypical lymphoid cells with
circumferential hairy projections. TRAP was positive in 9 patients (81.8 %).
Immunophenotyping was done in six cases, four were confirmed as HCL and two were
diagnosed as HCL-v. The patients treated with Cladribine generally had a good
response. The characteristic morphology of the hairy cells; along with
correlation with the clinical features, TRAP positivity and immunophenotyping by
flow cytometry is essential for diagnosis. Treatment response with Cladribine is
good and has prolonged remission rates.
PMID- 25114405
TI - Frequency of alloantibodies among chronic renal failure patients in red sea
state.
AB - Chronic renal failure patients need regular blood transfusion support to treat
anemia and the development of erythrocyte alloantibodies complicates transfusion
therapy. The aim of this study was to determine the frequency and specificity of
alloantibodies against red cell antigens in CRF patients. This was a descriptive
cross-sectional study done in the blood bank, Port Sudan, during the period of
May-September 2012. A total of 84 patients (58 male and 26 female) with CRF who
received at least one unit of RBC matched for ABO & Rh(D) antigens only were
enrolled. Sera were screened for the presence of alloantibody by antibody
screening test. The positive samples were subjected for antibody identification.
The incidence of alloantibody among CRF patients was 13.1 % and the most common
alloantibodies were Anti-c (27.3 %), anti-C (18.2 %), and anti-K (18.2 %). The
risk of alloimmunization among CRF patients was 4.8 % with the frequency of 13.1
% and Anti-c being the commonest alloantibodies identified.
PMID- 25114406
TI - Epstein-Barr Viral Load is Associated to Response in AIDS-Related Lymphomas.
AB - AIDS-related lymphoma (ARL) development is associated to immunodeficiency state
with proliferation of B-cells driven by HIV itself and EBV infection. However,
Epstein-Barr DNA is not detected in malignant cells of all ARL subtypes. A
prospective and controlled study to analyze EBV viral load (VL) in plasma and
peripheral blood mononuclear cells (PBMC) of ARL patients was performed to
analyze if Epstein-Barr VL could be related to response in these patients.
Fifteen patients with ARL were included in this study with measurement of EBV VL
at three different periods of time: at lymphoma diagnosis, upon completion of
chemotherapy, and 3 months after. Two control groups composed by HIV-negative and
HIV-positive patients were also evaluated for EBV VL comparison. In situ
hybridization for EBER was performed on diagnostic samples of all ARL patients.
Median EBV VL in PBMC and plasma had a significant decrease (p = 0.022 and p =
0.003, respectively) after ARL treatment. EBER was positive in 7 (46.7 %) cases.
Median EBV VL in PBMC before lymphoma treatment in patients positive for EBER was
significantly higher compared to EBER negative cases (p = 0.041). Reduction of
EBV viral load during treatment of lymphoma could be predictive of response. EBER
expression was associated to advanced stages of disease and worse immune status.
Our study suggests that measurement of EBV VL during ARL treatment could be used
as a marker for response, but further studies are needed to validate this
association.
PMID- 25114407
TI - Pleural effusion as an unusual initial presentation of acute myeloid leukemia.
AB - Pleural effusions in acute myeloid leukemia (AML) can have wide differential
diagnosis, however AML presenting as pleural effusion with leukemic infiltration
is rarely documented. A 22 year old male presented with pleural effusion for 3
months and subsequently diagnosed as AML M2, which prompted us for this
communication.
PMID- 25114408
TI - Rare case of acquired haemophilia and lupus anticoagulant.
AB - Acquired haemophilia or factor VIII (FVIII) deficiency, caused by FVIII inhibitor
antibodies, is a very rare condition that commonly results in severe haemorrhagic
complications. We report a case of acquired haemophilia presenting with multiple
bluish patches affecting face, neck, upper & lower limbs, history of gum bleeding
and left knee haemarthrosis. The patient was found to have acquired FVIII
inhibitor and lupus anticoagulant (LAC). The simultaneous presence of LAC and
FVIII inhibitor is exceedingly rare. The differentiation between these two
conditions is crucial, because both result in a prolongation of the activated
partial thromboplastin time test, which does not correct when mixed with the
plasma of a normal control; however, the clinical manifestations range from
thrombosis in the presence of LAC to massive haemorrhage with FVIII inhibitors.
PMID- 25114409
TI - Pseudo chediak-higashi granules in acute lymphoblastic leukemia: a rare entity.
AB - Pseudo-Chediak-Highashi granules are giant cytoplasmic inclusions commonly
encountered in myeloblasts or other myeloid precursors in acute myeloid leukemia
and myelodysplastic syndromes. They derive their name from the inherited Chediak
Higashi syndrome that presents with oculocutaneous albinism, chronic infections
and platelet dense granule deficiency. We report possibly the third case in world
literature where these granules were seen in the blast cells of acute
lymphoblastic leukemia in a 15-year-old male.
PMID- 25114410
TI - Hemophagocytic lymphohistiocytosis.
AB - Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder characterized by
uncontrolled inflammation due to defective immune response. It may be familial or
acquired, but both share a common feature of threatening the life of a patient
and may lead to death unless treated by appropriate treatment. Here in we report
a case of adult HLH.
PMID- 25114411
TI - A rare case of anti-jk3 antibody detected on pre-transfusion investigation.
AB - We report a 47-year-old Malay lady, para 4 + 1, with known medical history of
hypertension whom presented at Emergency Department with severe anaemia, most
likely secondary to menorrhagia caused by uterine fibroids. Her haemoglobin was
5.5 g/dl and she was transfused with three units of packed cell without any
adverse reaction, her haemoglobin level increased to 9.8 g/dl. She was then
planned for total abdominal hysterectomy and bilateral salpingo-oophorectomy
later. Four months later when she came for the elective surgery, her pre
transfusion investigations showed blood group as B Rh D positive, with a probable
R1R1 phenotype. Her antibody screening was positive in all the three panel cells.
Further testings showed a negative Direct Coomb's test and negative autocontrol,
antibody identification showed pan-agglutination reaction on all 11 panel cells
with enzyme enhancement. Patient's red cell phenotype was Jk(a-b-). Anti-Jk3 was
suspected and further confirmed in the reference laboratory by phenotyping as
well as negative urea lysis test. This case report highlights an extremely rare
but clinically significant anti-JK3 antibody detected during pretransfusion
testing. This phenotype is rare in the white population, more commonly seen in
various polynesians. Increased awareness among the blood bank personnel regarding
the variability of the blood group phenotype and the capricious nature of the
Kidd antibodies may contribute to the better management of these patients.
PMID- 25114412
TI - Chronic idiopathic non-cirrhotic portal vein thrombosis treated with a mesocaval
shunt procedure and anticoagulation.
AB - Portal vein thrombosis (PVT) was first reported in 1868 by Balfour and Stewart
and is a medical condition in which the lumen of the portal vein is completely or
partially obstructed due to the presence of a thrombus [1]. Inherited (Factor V
Leiden and Prothrombin gene mutation G201210A, Protein C, S and Anti thrombin III
deficiency) and acquired thrombophilias (Lupus Anticoagulant, myeloproliferative
diseases, malignancy, surgery and trauma) account for majority of the cases of
PVT.
PMID- 25114413
TI - Platelet satellitism: a rare, interesting, in vitro phenomenon.
AB - Platelet satellitism is a unique, uncommon, in vitro phenomenon seen in
peripheral blood smears prepared from EDTA-mixed blood. This is seen in the form
of platelets adhering to polymorphonuclear leucocytes imparting a rosette-like
appearance. There is no definite causal association with any disease. The cause
may be immunological or non-immunological. Severe rosetting may lead to a
misdiagnosis of thrombocytopenia unless peripheral smears are examined. Here, we
describe a case of incidentally detected platelet satellitism in a healthy 48
year old male subject during a routine check-up.
PMID- 25114414
TI - Fascia lata allograft bridging of a rotator cuff tear in a rabbit animal model.
AB - PURPOSE: Despite advances in surgical treatment options, large rotator cuff (r-c)
tears still represent a challenge for orthopedic surgeons. The purpose of this
study was to evaluate the temporary and spatial histological incorporation of
fascia lata allografts, used for bridging artificially created defects of the r
c. MATERIALS AND METHODS: Seventy-two rabbits were divided into two groups and a
supraspinatus tendinous defect was created. Half of the rabbit population
underwent repair only, while in the other half, the defect was bridged utilizing
fascia lata allograft. The animals were euthanized at 2, 4, and 6 weeks
postoperative. Half of the specimens were evaluated histologically and the other
half underwent mechanical testing. RESULTS: There was an increased remodeling
activity, fibroblastic in growth and strong presence of collagen fibers observed
at 6 weeks on both groups. A gradually increasing mechanical strength was noticed
by week 6 and increased toughness was also found at the same time period. There
was no significant difference observed between the two groups regarding their
histological and mechanical properties. CONCLUSIONS: In the difficult scenario of
a large irreparable tear where the simple suture of the remaining r-c is
impossible, allograft bridging, could be used with satisfactory results. CLINICAL
RELEVANCE: Treatment Study, Level 1.
PMID- 25114415
TI - Complications after subpectoral biceps tenodesis using a dual suture anchor
technique.
AB - PURPOSE: A variety of fixation techniques for subpectoral biceps tenodeses have
been described including interference screw and suture anchor fixation.
Biomechanical data suggests that dual suture anchor fixation has equivalent
strength compared to interference screw fixation. The purpose of the study is to
determine the early complication rate after subpectoral biceps tenodesis
utilizing a dual suture anchor technique. MATERIALS AND METHODS: A total of 103
open subpectoral biceps tenodeses were performed over a 3-year period using a
dual suture anchor technique. There were 72 male and 31 female shoulders. The
average age at the time of tenodesis was 45.5 years. 41 patients had a minimum of
6 months clinical follow-up (range, 6 to 45 months). The tenodesis was performed
for biceps tendonitis, superior labral tears, biceps tendon subluxation, biceps
tendon partial tears, and revisions of prior tenodeses. RESULTS: There were a
total of 7 complications (7%) in the entire group. There were 4 superficial wound
infections (4%). There were 2 temporary nerve palsies (2%) resulting from the
interscalene block. One patient had persistent numbness of the ear and a second
patient had a temporary phrenic nerve palsy resulting in respiratory dysfunction
and hospital admission. One patient developed a pulmonary embolism requiring
hospital admission and anticoagulation. There were no hematomas, wound
dehiscences, peripheral nerve injuries, or ruptures. In the sub-group of patients
with a minimum of 6 months clinical follow-up, the only complication was a single
wound infection treated with oral antibiotics. CONCLUSIONS: Subpectoral biceps
tenodesis utilizing a dual suture anchor technique has a low early complication
rate with no ruptures or deep infections. The complication rate is comparable to
those previously reported for interference screw subpectoral tenodesis and should
be considered as a reasonable alternative to interference screw fixation. LEVEL
OF EVIDENCE: Level IV-Retrospective Case Series.
PMID- 25114416
TI - Sudden severe postoperative dyspnea following shoulder surgery: Remember
inadvertent phrenic nerve block due to interscalene brachial plexus block.
AB - Advanced imaging techniques, improved operative techniques, and instrumentation
combined with better patient awareness and expectations have resulted in an
exponential increase in upper limb surgical procedures during recent times.
Surgical teams expect superior analgesia and regional blocks have matched these
expectations quite often resulting in improved patient satisfaction and early
rehabilitation to achieve best results. Ultrasound-guided interscalene brachial
plexus block (ISB) is commonly used to provide analgesia for procedures involving
shoulder girdle. We report a case of symptomatic hemi-diaphragmatic paresis (HDP)
due to the phrenic nerve block following ISB for arthroscopic sub-acromial
decompression of the shoulder presenting as severe postoperative dyspnea. There
is strong evidence of HDP following ISB in anesthetic literature, but not
reported in related surgical specialties such as orthopedics. We wish to inform
upper-limb surgeons and educate junior doctors and other ancillary staff working
in upper-limb units to be aware of this serious but reversible complication.
PMID- 25114417
TI - Osteochondral humeral head fracture after posterior shoulder subluxation: A case
report.
AB - Traumatic posterior shoulder subluxations are rare entities which require
clinical suspicion upon presentation. Although literature presents many sequels
of posterior shoulder subluxations, we have not come across any shearing type
osteochondral fracture in the literature. In this case report we present
diagnosis, treatment and follow-up results of this rare fracture in a 26-year-old
male following a fall from a motorcycle.
PMID- 25114418
TI - An unusual cause of mass in the shoulder: A primary hydatid cyst.
AB - A hydatid cyst is a zoonotic infection which may affect any organ and tissue,
particularly the liver and the lung. Primary muscular hydatid cysts comprise less
than 0.7-3% of the cases. The hydatid cysts must be kept in mind to avoid a
diagnostic puncture in cystic lesions to avoid the spreading of the disease. In
this case report, we present an exceptionally rare case with an unusual
localization of a primary hydatid cyst in the left deltoid muscle.
PMID- 25114419
TI - Myositis ossificans of the humeral insertion of pectoralis major.
AB - We report on a rare case of myositis ossificans of the humeral insertion of
pectoralis major muscle following a single episode of trauma which, to our
knowledge, has not previously been documented.
PMID- 25114420
TI - What's new in emergencies, trauma, and shock? Heparin in severe traumatic brain
injury: Beyond venous thromboembolism prevention?
PMID- 25114421
TI - Early initiation of prophylactic heparin in severe traumatic brain injury is
associated with accelerated improvement on brain imaging.
AB - BACKGROUND: Venous thromboembolic prophylaxis (VTEp) is often delayed following
traumatic brain injury (TBI), yet animal data suggest that it may reduce cerebral
inflammation and improve cognitive recovery. We hypothesized that earlier VTEp
initiation in severe TBI patients would result in more rapid neurologic recovery
and reduced progression of brain injury on radiologic imaging. STUDY DESIGN:
Medical charts of severe TBI patients admitted to a level 1 trauma center in 2009
2010 were queried for admission Glasgow Coma Scale (GCS), head Abbreviated Injury
Scale, Injury Severity Score (ISS), osmotherapy use, emergency neurosurgery, and
delay to VTEp initiation. Progression (+1 = better, 0 = no change, -1 = worse) of
brain injury on head CTs and neurologic exam (by bedside MD, nurse) was collected
from patient charts. Head CT scan Marshall scores were calculated from the
initial head CT results. RESULTS: A total of 22, 34, and 19 patients received
VTEp at early (<3 days), intermediate (3-5 days), and late (>5 days) time
intervals, respectively. Clinical and radiologic brain injury characteristics on
admission were similar among the three groups (P > 0.05), but ISS was greatest in
the early group (P < 0.05). Initial head CT Marshall scores were similar in early
and late groups. The slowest progression of brain injury on repeated head CT
scans was in the early VTEp group up to 10 days after admission. CONCLUSION:
Early initiation of prophylactic heparin in severe TBI is not associated with
deterioration neurologic exam and may result in less progression of injury on
brain imaging. Possible neuroprotective effects of heparin in humans need further
investigation.
PMID- 25114422
TI - Acute Flaccid paralysis in adults: Our experience.
AB - Acute flaccid paralysis (AFP) is a complex clinical syndrome with a broad array
of potential etiologies that vary with age. We present our experience of acute
onset lower motor neuron paralysis. MATERIALS AND METHODS: One hundred and thirty
three consecutive adult patients presenting with weakness of duration less than
four weeks over 12 months period were enrolled. Detailed history, clinical
examination, and relevant investigations according to a pre-defined diagnostic
algorithm were carried out. The patients were followed through their hospital
stay till discharge or death. RESULTS: The mean age was 33.27 (range 13-89) years
with male preponderance (67.7%). The most common etiology was neuroparalytic
snake envenomation (51.9%), followed by Guillain Barre syndrome (33.1%),
constituting 85% of all patients. Hypokalemic paralysis (7.5%) and acute
intermittent porphyria (4.5%) were the other important conditions. We did not
encounter any case of acute polio mylitis in adults. In-hospital mortality due to
respiratory paralysis was 9%. CONCLUSION: Neuroparalytic snakebite and Guillain
Barre syndrome were the most common causes of acute flaccid paralysis in adults
in our study.
PMID- 25114423
TI - Ultrasound: A novel tool for airway imaging.
AB - CONTEXT: The scope of ultrasound is emerging in medical science, particularly
outside traditional areas of radiology practice. AIMS: We designed this study to
evaluate feasibility of bedside sonography as a tool for airway assessment and to
describe sonographic anatomy of airway. SETTINGS AND DESIGN: A prospective,
clinical study. MATERIALS AND METHODS: We included 100 adult, healthy volunteers
of either sex to undergo airway imaging systemically starting from floor of the
mouth to the sternal notch in anterior aspect of neck by sonography. RESULTS: We
could visualize mandible and hyoid bone as a bright hyperechoic structure with
hypoechoic acoustic shadow underneath. Epiglottis, thyroid cartilage, cricoid
cartilage, and tracheal rings appeared hypoechoic. Vocal cords were visualized
through thyroid cartilage. Interface between air and mucosa lining the airway
produced a bright hyperechoic linear appearance. Artifacts created by
intraluminal air prevented visualization of posterior pharynx, posterior
commissure, and posterior wall of trachea. CONCLUSIONS: Ultrasound is safe,
quick, noninvasive, repeatable, and bedside tool to assess the airway and can
provide real-time dynamic images relevant for several aspects of airway
management.
PMID- 25114424
TI - Arrival time pattern and waiting time distribution of patients in the emergency
outpatient department of a tertiary level health care institution of North India.
AB - BACKGROUND: Emergency Department (ED) of tertiary health care institute in India
is mostly overcrowded, over utilized and inappropriately staffed. The challenges
of overcrowded EDs and ill-managed patient flow and admission processes result in
excessively long waits for patients. AIM: The objective of the present study was
to analyze the patient flow system by assessing the arrival and waiting time
distribution of patients in an Emergency out Patient Department (EOPD). MATERIALS
AND METHODS: This short cross-sectional descriptive study was conducted in the
EOPD of a Tertiary level health care Institution in North India in the month of
May, 2011. The data was obtained from 591 patients, who were present in the EOPD
during the month of May, 2011. The waiting time, inter arrival time between two
consecutive patients were calculated in addition to the daily census data
(discharge rate, admission rate and transfer out rates etc.) of the emergency.
RESULTS: Arrival time pattern of patients in the EOPD was highly stochastic with
the peak arrival hours to be 9.00-12.00 h in which around 26.3% patients arrived
in the EOPD. The primary waiting areas of patients included patients under
observation (29.6%); waiting for routine diagnostic tests (16.4%) and waiting for
discharge (14.6%). Around 71% patients were waiting due to reasons within
emergency complex. CONCLUSION: The patient flow of the ED could only be addressed
by multifaceted, multidisciplinary and hospital wide approach.
PMID- 25114425
TI - Awareness about basic life support and emergency medical services and its
associated factors among students in a tertiary care hospital in South India.
AB - BACKGROUND: The knowledge and skills about the basic life support (BLS) and the
advanced life support are the most important determining factors of the
cardiopulmonary resuscitation (CPR) success rates. OBJECTIVES: To determine the
level of awareness on BLS and skills among undergraduate and postgraduate
students of medical and dental profession, as well as nursing students and
interns in a tertiary care hospital. MATERIALS AND METHODS: This descriptive
cross-sectional study was conducted in a tertiary care hospital in South India.
The awareness level on BLS and factors associated which include age, sex, level
of training (undergraduate, internship, and postgraduate groups), course of study
(nursing, dental, and medical groups), and previous exposure to BLS were assessed
by using a structured questionnaire. The association of these variables with
awareness level was assessed by independent t test, analysis of variance, and
linear regression analysis. RESULTS: Among 520 study subjects, 229 were students,
171 were interns, and 120 were postgraduate students. The overall mean score of
awareness was 4.16 +/- 1.40 (score range: 0-10). Age, sex, level of training,
course of study, and previous exposure to BLS were significantly associated with
awareness level in univariate analysis (P < 0.05). Linear regression model also
showed that all the above variables were significantly associated with awareness
level (P < 0.05). About 322 (61.9%) subjects attributed lack of awareness about
BLS to lack of available professional training. About 479 (92.1%) responded that
BLS training should be a part of medical curriculum. CONCLUSION: Awareness level
on BLS is below average indicating the importance of professional training at all
levels in a tertiary care health institution.
PMID- 25114426
TI - Management of isolated sternal fractures using a practical algorithm.
AB - BACKGROUND: The implementation of seat belt legislation has led to an increase in
the frequency of isolated sternal fractures (ISFs) in motor vehicle crash. AIMS:
We reviewed retrospectively the medical records of our tertiary center in order
to find out the frequency of ISFs, review our experience in their management, and
define the mean length of hospitalization. MATERIALS AND METHODS: From January
2008 to April 2012, 64 patients were admitted to the accident and emergency
department of the University Hospital of Larissa, Greece, suffering from sternal
fractures (SFs). Of these 64 patients, 45 had sustained ISF, while the remaining
19 had SF and additional injuries (intrathoracic and extrathoracic). The files of
these 45 patients were further investigating as concerning the mechanism of
injury, hospitalization days, morbidity, and mortality. RESULTS: All the patients
had been involved in motor vehicle crashes and most of them were wearing seat
belts during the accident (91%). The hospital length of stay (LOS) was 1.85 +/-
1.67. All the patients had upon admission chest radiograms, serial
electrocardiographs (ECGs), echocardiograms, and cardiac enzyme levels. Two
patients had abnormal ECG and abnormal cardiac enzymes which contributed in
prolonged hospitalization. However, there was no incidence of cardiac
complications or deaths. CONCLUSIONS: ISFs, with normal electrocardiogram,
cardiac enzymes, and chest X-ray in the absence of complications, require no
further investigation.
PMID- 25114427
TI - Epidemiology of trauma in an acute care hospital in Singapore.
AB - BACKGROUND: Trauma injury is the leading cause of mortality and hospitalization
worldwide and the leading cause of potential years of productive life lost.
Patients with multiple injuries are prevalent, increasing the complexity of
trauma care and treatment. Better understanding of the nature of trauma risk and
outcome could lead to more effective prevention and treatment strategies.
MATERIALS AND METHODS: A retrospective review of 1178 trauma patients with Injury
Severity Score (ISS) >= 9, who were admitted to the Acute and Emergency Care of
an acute care hospital between January 2011 and December 2012. The statistical
analysis included calculation of percentages and proportions and application of
test of significance using Pearson's chi-square test or Fisher's exact test where
appropriate. RESULTS: Over the study period, 1178 patients were evaluated, 815
(69.2%) males and 363 (30.8%) females. The mean age of patients was 52.08 +/-
21.83 (range 5-100) years. Falls (604; 51.3%) and road traffic accidents (465;
39.5%) were the two most common mechanisms of injury. Based on the three most
common mechanisms of injury, i.e. fall on the same level, fall from height, and
road traffic accident, the head region (484; 45.40%) was the most commonly
injured in the body, followed by lower limbs (377; 35.37%) and thorax (299;
28.05%). CONCLUSION: Fall was the leading cause of injury among the elderly
population with road traffic injuries being the leading cause among the younger
group. There is a need to address the issues of injury control and prevention in
these areas.
PMID- 25114428
TI - Occupational health surveillance: Pulmonary function testing in emergency
responders.
AB - Emergency responders may be exposed to a variety of fumes, gases, and
particulates during the course of their job that can affect pulmonary function
(PF) and require the use of respiratory protection. This investigation used
occupational health monitoring examination data to characterize PF in a
population currently employed as emergency responders. PF tests for workers who
required health examinations to ensure fitness for continued respirator use were
compared to the National Health and Nutrition Examination Survey (NHANES) III Raw
Spirometry database to determine if decreased PF was associated with employment
as an emergency responder. The results of this research indicated that the
emergency responders experienced a modest, but statistically significant,
increase in forced expiratory volume in 1 second (FEV1) and forced vital capacity
(FVC) mean values over the NHANES III population in both total and stratified
analyses, including stratification by age, gender, height, and smoking history.
Results are likely due to a combination of effectively controlled exposures in
the workplace, and the healthy worker effect among long-term workers. PF testing
required by the Occupational and Safety Health Administration (OSHA) has
substantial utility for conducting occupational surveillance at the population
level. In this investigation, we were able to quickly evaluate if abnormal PF
existed in an industrial sector known to have exposures that, when uncontrolled,
can lead to PF impairment.
PMID- 25114429
TI - Procedural sedation for pediatric patients in the emergency department at King
Khalid University Hospital, Riyadh, K.S.A.
AB - Procedural sedation and analgesia (PSA) has become the standard of care for
diagnostic and therapeutic procedures undertaken in the Emergency Department
(ED). In the Pediatric Emergency Department (PED) of King Khalid University
Hospital (KKUH), which is a major teaching hospital in Riyadh Kingdom of Saudi
Arabia we developed a standard protocol for PSA since 2005. The aim of this
article is to report the experience at KKUH in pediatric PSA. OBJECTIVES: To
report the experience at KKUH in pediatric PSA. OBJECTIVES: To report the
experience at KKUH in pediatric PSA. MATERIALS AND METHODS: Retrospective cross
sectional study of all cases who underwent PSA for painful procedures in
Pediatric Emergency at KKUH from December 2005 to July 2008. RESULTS: A total of
183 patients were reviewed. 179 patients were analyzed. Age ranges from 4 months
to 13 years (mean 6 years). Nearly 66% were male. Ketamine was the most commonly
used drug. Reduction of fracture/dislocation was the most common indication for
sedation. Adverse events were identified in only 5.6% of patients. Vomiting was
the most common recorded side-effect. The length of stay in the ED was ranging
from 28 to 320 min (mean 111 min). CONCLUSION: Intravenous Ketamine is a
consistently effective method of producing a rapid, brief period of adequate
sedation and analgesia in children in the ED with no major side-effects noted in
our experience.
PMID- 25114430
TI - Effects of aminoguanidine, a potent nitric oxide synthase inhibitor, on
myocardial and organ structure in a rat model of hemorrhagic shock.
AB - BACKGROUND: Nitric oxide (NO) has been shown to increase following hemorrhagic
shock (HS). Peroxynitrite is produced by the reaction of NO with reactive oxygen
species, leads to nitrosative stress mediated organ injury. We examined the
protective effects of a potent inhibitor of NO synthase, aminoguanidine (AG), on
myocardial and multiple organ structure in a rat model of HS. MATERIALS AND
METHODS: Male Sprague Dawley rats (300-350 g) were assigned to 3 experimental
groups (n = 6 per group): (1) Normotensive rats (N), (2) HS rats and (3) HS rats
treated with AG (HS-AG). Rats were hemorrhaged over 60 min to reach a mean
arterial blood pressure of 40 mmHg. Rats were treated with 1 ml of 60 mg/kg AG
intra-arterially after 60 min HS. Resuscitation was performed in vivo by the
reinfusion of the shed blood for 30 min to restore normo-tension. Biopsy samples
were taken for light and electron microscopy. RESULTS: Histological examination
of hemorrhagic shocked untreated rats revealed structural damage. Less
histological damage was observed in multiple organs in AG-treated rats. AG
treatment decreased the number of inflammatory cells and mitochondrial swollen in
myocardial cells. CONCLUSION: AG treatment reduced microscopic damage and injury
in multiple organs in a HS model in rats.
PMID- 25114431
TI - The 2014 Academic College of Emergency Experts in India's Education Development
Committee (EDC) White Paper on establishing an academic department of Emergency
Medicine in India - Guidelines for Staffing, Infrastructure, Resources,
Curriculum and Training.
AB - Emergency medicine services and training in Emergency Medicine (EM) has developed
to a large extent in developed countries but its establishment is far from
optimal in developing countries. In India, Medical Council of India (MCI) has
taken great steps by notifying EM as a separate specialty and so far 20 medical
colleges have already initiated 3-year training program in EM. However, there has
been shortage of trained faculty, and ambiguity regarding curriculum, rotation
policy, infrastructure, teachers' eligibility qualifications and scheme of
examination. Academic College of Emergency Experts in India (ACEE-India) has been
a powerful advocate for developing Academic EM in India. The ACEE's Education
Development Committee (EDC) was created to chalk out guidelines for staffing,
infrastructure, resources, curriculum, and training which may be of help to the
MCI and the National Board of Examinations (NBE) to set standards for starting 3
year training program in EM and develop the departments of EM as centers of
quality education, research, and treatment across India. This paper has made an
attempt to give recommendations so as to provide a uniform framework to the
institutions, thus guiding them towards establishing an academic Department of EM
for starting the 3-year training program in the specialty of EM.
PMID- 25114432
TI - Establishing consensus on the definition of an isolated hip fracture for trauma
system performance evaluation: A systematic review.
AB - BACKGROUND: Risk-adjusted mortality is widely used to benchmark trauma center
care. Patients presenting with isolated hip fractures (IHFs) are usually excluded
from these evaluations. However, there is no standardized definition of an IHF.
We aimed to evaluate whether there is consensus on the definition of an IHF used
as an exclusion criterion in studies evaluating the performance of trauma centers
in terms of mortality. MATERIALS AND METHODS: We conducted a systematic review of
observational studies. We searched the electronic databases MEDLINE, EMBASE,
BIOSIS, The Cochrane Library, CINAHL, TRIP Database, and PROQUEST for cohort
studies that presented data on mortality to assess the performance of trauma
centers and excluded IHF. A standardized, piloted data abstraction form was used
to extract data on study settings, IHF definitions and methodological quality of
included studies. Consensus was considered to be reached if more than 50% of
studies used the same definition of IHF. RESULTS: We identified 8,506 studies of
which 11 were eligible for inclusion. Only two studies (18%) used the same
definition of an IHF. Three (27%) used a definition based on Abbreviated Injury
Scale (AIS) Codes and five (45%) on International Classification of Diseases
(ICD) codes. Four (36%) studies had inclusion criteria based on age, five (45%)
on secondary injuries, and four (36%) on the mechanism of injury. Eight studies
(73%) had good overall methodological quality. CONCLUSIONS: We observed important
heterogeneity in the definition of an IHF used as an exclusion criterion in
studies evaluating the performance of trauma centers. Consensus on a standardized
definition is needed to improve the validity of evaluations of the quality of
trauma care.
PMID- 25114434
TI - Newer nonconventional modes of mechanical ventilation.
AB - The conventional modes of ventilation suffer many limitations. Although they are
popularly used and are well-understood, often they fail to match the patient
based requirements. Over the years, many small modifications in ventilators have
been incorporated to improve patient outcome. The ventilators of newer generation
respond to patient's demands by additional feedback systems. In this review, we
discuss the popular newer modes of ventilation that have been accepted in to
clinical practice. Various intensive care units over the world have found these
modes to improve patient ventilator synchrony, decrease ventilator days and
improve patient safety. The various modes discusses in this review are: Dual
control modes (volume assured pressure support, volume support), Adaptive support
ventilation, proportional assist ventilation, mandatory minute ventilation, Bi
level airway pressure release ventilation, (BiPAP), neurally adjusted ventilatory
assist and NeoGanesh. Their working principles with their advantages and clinical
limitations are discussed in brief.
PMID- 25114433
TI - Surgical management in treatment of Jehovah's witness in trauma surgery in Indian
subcontinent.
AB - The Jehovah's Witness religion is a Christian movement, founded in the US in the
1870s, with 7 million followers worldwide with only 0.002% in India. There is
minimal to complete absence of awareness about the existence of this community in
our society. Astonishing is that fact that among medical professionals, there is
almost no awareness about this unique population, regarding the fact that they
completely refuse of blood transfusion even if it leads to their death. This is
integral to their faith. Besides legal and ethical issues in treating these group
of patients, the biggest challenge exist even in the western world is their
management in trauma scenario where few options exist. We have discussed the
issues and recommendations in management in trauma scenario in our Indian
subcontinent.
PMID- 25114436
TI - Operative management of splenic injury in a patient with proteus syndrome.
AB - A 20-year-old female with Proteus syndrome sustained splenic injury after fall
from a bike. She was initially managed non-operatively at a different hospital
for three days and was then referred to our level I trauma center in view of
increasing abdominal pain and distention. On admission in the Emergency
Department (ED), her pulse rate was 120 per minute and blood pressure was 108/68
mm Hg. Clinical examination showed a distended abdomen with left hypochondrial
pain. Ultrasonogram (USG) and Computed Tomography (CT) of the abdomen showed
splenomegaly and grade III splenic injury with significant hemoperitoneum. Her
hemoglobin was 2.9 g/dl with packed cell volume (PCV) of 12%. In view of low
hemoglobin and possibility of pathologic spleen, splenectomy was done.
Microscopic examination of the spleen showed hemangiolymphangioma. The patient
was discharged on the 5(th) post-operative day and is doing well at 6 months of
follow-up.
PMID- 25114435
TI - The therapeutic challenges of degloving soft-tissue injuries.
AB - BACKGROUND: Degloving soft-tissue injuries are serious and debilitating
conditions. Deciding on the most appropriate treatment is often difficult.
However, their impact on patients' outcomes is frequently underestimated.
OBJECTIVES: We aimed to study the incidence, clinical presentation, management
and outcome of degloving soft-tissue injuries. MATERIALS AND METHODS: We
conducted a narrative traditional review using the key words; degloving injury
and soft-tissue injuries through search engines PubMed, Science Direct, and
Scopus. RESULTS: There are several therapeutic options for treating degloving
soft-tissue injuries; however, no evidence-based guidelines have been published
on how to manage degloving soft-tissue injuries, although numerous articles
outline the management of such injuries. CONCLUSION: Degloving soft-tissue
injuries are underreported and potentially devastating. They require early
recognition, and early management. A multidisciplinary approach is usually needed
to ensure the effective rehabilitation of these patients.
PMID- 25114437
TI - Bedside ultrasound diagnosis of intracardiac paperclip.
AB - Penetrating cardiac injuries are rarely reported in the literature. Foreign
bodies are rarely seen in the heart and most patients with penetrating cardiac
injuries die from hemorragic or pericardial tamponade before arriving at the
hospital. Bedside ultrasonography is a highly valuable and readily learned tool
that has expanded rapidly since its introduction more than 20 years ago. Our case
was a 23-year-old convict brought to the emergency department (ED) with a history
of continuous chest pain in the upper area of the left side of the chest for one
week. Focused Cardiac Sonography (FOCUS) which was performed by emergency
physician showed a strong echogenic linear structure with comet tail artifact,
free floating in the mid-segment of the left ventricule. Exact localizations of
the paperclips within the chest was obtained with multidetector computed
tomography and one of them was seen in the left ventricular cavity. FOCUS plays a
crucial role in these patients by diagnosing the injury and detecting the
complications in emergency department.
PMID- 25114438
TI - A patient fatality following the ingestion of a small amount of chlorfenapyr.
AB - Chlorfenapyr has been used worldwide for agricultural pest control since 1995.
Despite its widespread use, acute human poisoning data are insufficient; only a
small number of fatalities from chlorfenapyr poisoning have been reported. The
signs and symptoms of chlorfenapyr toxicity include nausea, vomiting, fever,
rhabdomyolysis, among others. In addition, central nervous system effects in
association with delayed toxicity have also been observed. Here, we detail a
fatality resulting from delayed chlorfenapyr toxicity following the ingestion of
a small amount of pesticide.
PMID- 25114439
TI - Recurrent posterior reversible encephalopathy syndrome of the brainstem in a
hypertensive patient with end-stage renal disease.
AB - A 59-year-old man with end-stage renal disease was brought to our emergency
department with complaints of headache, nausea, dysarthria, tic, and weakness
involving the bilateral arms and legs. He had the similar episode 4 month before,
when he was treated elsewhere. The patient had received hemodialysis three times
per week. His medications included for hypertension. On examination at his
arrival, he was alert with reduced concentration and incoherent thoughts. The
blood pressure was 181/87 mmHg and other vital signs were normal. Neurological
findings showed slight dysarthria and slow movements but no other abnormalities.
Laboratory data showed increased serum creatinine and potassium presumably for a
session of periodical hemodialysis but normal sodium concentration. His
cerebrospinal fluid examination was normal. We treated him by hemodialysis.
Diagnosis of PRES was most likely because of the clinical features and the MRI
findings. His symptoms had disappeared immediately and completely after we
controlled high blood pressure. MRI on 13 days after admission showed the
improvement of the abnormal findings. Although the pathophysiology of PRES is
incompletely understood, renal failure was known as one of the risk factors. A
relative lack of sympathetic innervation of posterior circulation could not
protect the area when severe hypertension makes auto-regulatory control
collapsed. However, PRES of the brainstem is uncommon although the posterior
circulation involves it. Because control of his hypertension was not appropriate
in the outpatient settings before this event, it could have contributed to the
recurrence in this patient.
PMID- 25114440
TI - Acute aortic dissection is independent of weather conditions but statistically
correlates with day of the week.
PMID- 25114441
TI - Emergency hepatic artery embolization in a patient with post-traumatic ruptured
hepatic artery pseudoaneurysm.
PMID- 25114442
TI - A case of transient left bundle branch block after a cervical wound.
PMID- 25114443
TI - Hair today, gone tomorrow.
PMID- 25114444
TI - A review of psychiatric disorders comorbidities in patients with alopecia areata.
AB - This is a review of psychiatric problems in patients with alopecia areata (AA).
The electronic database of MedLine/PubMed was searched using the determined
keywords. The rate of depression in children and adolescents with AA is up to
50%. Stressful life events are associated with AA. A rate of 39% for generalized
anxiety disorders was reported. AA is highly associated with obsessive compulsive
disorder (35.7%) in children and adolescents. Schizophrenia tended to be less
seen in AA patients.
PMID- 25114445
TI - Association between androgenetic alopecia and coronary artery disease in young
male patients.
AB - BACKGROUND: Several studies have demonstrated an association between androgenetic
alopecia (AGA) and cardiovascular disease. Still controversies exist regarding
the association. Are they truly associated? OBJECTIVE: The purpose of the present
study was to assess the prevalence of AGA and establish its association in young
(<45 years) Asian Indian Gujarati male patients having coronary artery disease
(CAD). MATERIALS AND METHODS: Case-control prospective multicentric study was
carried out on 424 men. Case group consisted of 212 male subjects having CAD
(Group 1) and another 212, either sibling or first degree male relative of the
case subjects (having no evidence of CAD) were considered as the control group
(Group 2). Age, total cholesterol, incidence of diabetes mellitus, and
hypertension were similar in both groups. The degree of alopecia was assessed
using the Norwood-Hamilton scale for men. Statistical analysis was performed
using Chi-square test. RESULTS: AGA was found in 80 (37.73%) young CAD patients
(Group 1), whereas 44 (20.7%) of patients had alopecia in the control group
(Group 2). There was statistically significant association between male AGA and
CAD (P = 0.001). Odds ratio was 2.70 (95% confidence interval [CI], 1.72 +/-
4.26). Statistically significant association was found between high grade
baldness (Grades IV-VII) and CAD in young men (P < 0.05). Odds ratio = 2.36 (95%
CI, 1.108 +/- 5.033). There is statistically significant association of AGA in
young Asian Gujarati male with CAD and the prevalence of AGA in young CAD patient
is 37.73%. CONCLUSION: This study implies early onset AGA in male is
independently associated with CAD, though mechanisms need to be investigated.
PMID- 25114446
TI - Quality of life in alopecia areata: a case-control study.
AB - BACKGROUND: Although alopecia areata (AA) is typically seen by medical staff as a
benign, not life-threatening cosmetic disease, some studies have found
significant impairment in quality of life (QL) in AA patients. There are no
studies that assess QL in Brazilian AA patients. OBJECTIVES: To evaluate QL in AA
patients, using the 36-item Short-Form Health Survey (SF-36). The most affected
SF-36 dimensions were compared to two culturally different AA QL studies.
MATERIALS AND METHODS: We performed a case-control study with 37 AA patients and
49 age- and sex-matched volunteer blood donors. The results of a Turkish and a
French study were compared to our results. RESULTS: The dimensions social
functioning (P = 0,001), role emotional (P = 0,019), and mental health (P =
0,000) scored statistically lower in the AA group in relation to controls,
suggesting a worse QL. Incomparison to the Turkish and French studies, we found:
(1) On the dimension role emotional, QL was equally impaired; (2) on the
dimension social functioning, it was not different than the Turkish study; (3)
social life of French AA patients was more affected; and (4) vitality and mental
health dimensions were significantly more affected in French and Turkish
patients. CONCLUSIONS: Impairment in QL in AA patients affected psychological,
emotional, and social aspects of theirlives. Despite the scores of SF-36
dimensions varied significantly among different cultural groups, impairment of QL
was found in all three studies; thus, we can suppose that these findings are not
linked to a specific culture.
PMID- 25114447
TI - 'Ho-ver'ing Over Alopecia Areata: Histopathological Study of 50 Cases.
AB - BACKGROUND: Different studies have been done on this topic, most of the older
studies on the vertical section confirm that peribulbar infiltrate is an
important finding, however the newer studies on the horizontal section, mention
decreased anagen to telogen ratio, decreased terminal to vellus hair ratio and a
decreased follicular count. These studies on horizontal (transverse sections)
have shown that transverse sectioning is superior and more diagnostic in studying
alopecias. However, these studies are based on multiple cut sections, because in
a single cut section, we may miss a few hair bulbs above or below, depending on
where the section is taken. Hence this makes it a time consuming, technically
challenging and expensive procedure. OBJECTIVES: 1. To compare the
histopathological features of single vertical section versus a single horizontal
section cut in the reticular dermis. 2. To determine if a single horizontal
section is sufficient to report a biopsy of alopecia areata compared to multiple
sections. MATERIALS AND METHODS: To compare the findings, in 50 patients with
localized alopecia areata, 25 sectioned horizontally and 25 vertically, single
section. Only three of the common findings, peribulbar infiltrate, intrabulbar
infiltrate and perifollicular microscarring was considered and reported. RESULTS:
Once the anagen to telogen ratio is excluded from the comparison, diagnosis made
on the basis of a single horizontal section is considered sufficient to give us
an aid toward the prognosis.
PMID- 25114448
TI - Trichofolliculoma presenting as lobulated mass: a rare presentation.
AB - Trichofolliculoma represents abortive differentiation of pluripotent skin cells
toward hair follicles. We present a case of an adult female with lobulated mass
involving the tip and dorsum of the nose for the last 15 years. The systemic and
radiological examinations were noncontributory. The clinical diagnosis was
thought to be dermoid cyst. The fine-needle aspiration cytology of the lobulated
mass was performed, and the cytology smears showed anucleate squames admixed with
sebaceous cells. The possibility of a benign skin adnexal lesion was suggested.
The biopsy was done, and the final diagnosis of trichofolliculoma was made. The
wide local excision of the mass was performed, and no recurrence was noted during
the follow-up of 1 year.
PMID- 25114449
TI - Three different dermoscopic view of three new cases with pilomatrixoma.
AB - Pilomatrixoma is a benign soft tissue neoplasm originated from follicular matrix
of hair and is also known as Malherbe's calcified epithelioma. Some lesions are
located on the skin and are usually misdiagnosed. A small number of patients had
been dermoscopically examined. In this article, three patients of pilomatrixoma
who had three different dermoscopic views were evaluated and discussed in
concordance with the literature.
PMID- 25114450
TI - Trichomegaly of eyelashes after treatment with erlotinib in carcinoma pancreas.
AB - Epidermal growth factor receptor (EGFR) inhibitors have been widely used for the
treatment of epithelial malignancies. A wide spectrum of skin toxicities have
been described in patients receiving EGFR inhibitors. Trichomegaly, especially of
the eyelashes is a rare side effect of this therapy. We report a case of
trichomegaly of eyelashes in a 39-year-old male, a case of carcinoma pancreas.
This side-effect of these medications gives prospects as a therapy to stimulate
the growth of hair.
PMID- 25114451
TI - The action of prostaglandins on ciliary hypertrichosis: a case report of
pachydermoperiostosis.
AB - Pachydermoperiostosis or primary hypertropic osteoarthropathy is a rare
hereditary disorder that was first described in 1868. It is characterized by
digital clubbing, pachydermia (thickening of the facial skin and/or scalp), and
periostosis (swelling of periarticular tissue and subperiosteal new bone
formation). We report a case of a patient with the complete form of the disease,
and with a unique appearance of the hair shaft and eyelashes. The authors propose
a possible mechanism to justify the abnormalities observed in the patient's hair
shafts regarding the metabolism of prostaglandins and its relationship with the
hair follicle physiological cycle.
PMID- 25114453
TI - Trichonodosis.
AB - Trichonodosis is characterized by knotted hair on the distal portion of the hair
shaft. This may be spontaneous or secondary to mechanical factors like vigorous
scratching or combing the hair. We report a case of spontaneous trichonodosis
with abnormal scalp and body hair.
PMID- 25114454
TI - Diode Laser: Permanent hair "Reduction" Not "Removal".
PMID- 25114452
TI - Primary idiopathic pseudopelade of brocq: five case reports.
AB - Pseudopelade of Brocq (PPB) is a rare, idiopathic self-limiting hair disorder
resulting in progressive cicatricial alopecia primarily involving the parietal
scalp and vertex. The general pathogenesis of scarring alopecias has been focused
on theories of stem cell failure and sebaceous gland destruction. Acquired
immunity, Borrelia infection and senescence of follicular stem cell reservoir
plays suspected role. It classically presents as porcelain white hypopigmented
and slightly depressed atrophic plaque. There is no standard treatment for PPB.
Here, we present five cases which were labeled as primary idiopathic PPB, as on
histopathology no specific changes of any cicatricial alopecia were seen.
PMID- 25114455
TI - Is there sufficient research data to use platelet-rich plasma in dermatology?
PMID- 25114456
TI - Trichotillomania associated with bipolar disorder and obsessive compulsive
disorder: pathoplasty or comorbidity?
PMID- 25114457
TI - Editorial.
PMID- 25114458
TI - Oral Cavity Cancers -Level v Metastasis.
PMID- 25114459
TI - Ultrasonic shears versus electrocautery in axillary dissection for breast cancer
a randomized controlled trial.
AB - Theoretical advantages of use of Ultrasonic shears include less tissue damage and
better sealing of lymphatic vessels. This may play a role in reducing prolonged
drainage following axillary dissection for breast cancer. We conducted a
prospective randomized controlled study to evaluate efficacy of ultrasonic shears
over cautery for axillary dissection. Between April 2011 and April 2013, 92
patients were randomized to undergo axillary dissection with either ultrasonic
shears (n = 46) or electrocautery (n = 46). Primary endpoints were time till
drain removal and cumulative axillary drainage. Categorical data were compared by
Pearson's chi-squared test. Continuous variables were compared by Independent t
test or Mann Whitney U test. Data was analyzed using SPSS version 18.0. Both
groups were comparable with respect to clinical and pathologic characteristics.
Clinical characteristics of mean age, body mass index, side of tumor, neoadjuvant
chemotherapy, and type of surgery (breast conservation or mastectomy) were
similar. Pathologic variables (weight of specimen, number of lymph nodes
harvested, pathologic T and N status, as well as grade of tumor) were also
comparable among the two groups. There was no statistically significant
difference in either primary endpoint of time till drain removal (15 vs. 14.5
days, p = 0.73) or cumulative axillary drainage (1,260 vs. 1,086.5 ml, p = 0.79).
Patient and disease characteristics among the two groups were similar. But, there
was no difference in either primary endpoint of cumulative axillary drainage or
time to drain removal. We conclude that there is no advantage to use of
ultrasonic shears over cautery in reducing drainage following axillary dissection
for breast cancer.
PMID- 25114460
TI - Role of frozen section in intraoperative assessment of ovarian masses: a tertiary
oncology center experience.
AB - Surgical management of ovarian lesions vary considerably depending on the nature
of the lesion. As the preoperative imaging and serum tumor marker levels are of
limited value in the proper categorization of ovarian lesions, intraoperative
pathological assessment is commonly requested for a primary diagnosis. Aim of the
study is to assess the accuracy of the frozen section in the diagnosis of ovarian
masses in our center and to analyze the causes of diagnostic discrepancies. In
this retrospective study, frozen section diagnosis of 233 cases of ovarian masses
was compared with the permanent section diagnosis. The overall accuracy of frozen
section was 91.85 %. The sensitivity of frozen section diagnosis for benign,
borderline and malignant tumors was 99.2, 88.46 and 82.95 % respectively. The
corresponding specificity was 96.5, 93.23 and 99.3 %. There were 19 discordant
cases including 18 false negative cases and one false positive case. Frozen
section is an important diagnostic tool to determine the nature of ovarian
masses. Careful macroscopic examination, evaluation of multiple sections along
with clinical and radiological findings helps to reduce false positive and false
negative results. Frozen section examination has limitations especially in cases
of borderline tumors. This modality is most effective when the pathologist and
surgeon are aware of the advantages and limitations.
PMID- 25114461
TI - Cervical node metastasis in T1 squamous cell carcinoma of oral tongue- pattern
and the predictive factors.
AB - BACKGROUND: The squamous cell carcinoma (SCC) of the oral tongue is a common
cancer in India. Elective lymphadenectomy is generally performed in all patients
with T2-T4 tumors. In this study we have tried to analyze the pattern and risk
factors associated with lymph node metastasis in T1 tongue cancers. METHODS: A
retrospective review of the records of 57 patients undergoing surgery for
treatment of T1 sqamous cell carcinoma of oral tongue was carried out. The
clinicopatological features of the tumor, pattern of nodal metastasis and the
risk factors associated with lymph node metastasis were studied. RESULTS: Totally
57 patients with T1 tumor underwent excision of the primary and modified neck
dissection (MND). Lymph node metastasis was found in 36.8 % of the patients.
Level I to Level II was the commonest site of metastasis. Skip metastasis at
level III and IV was found in 8.5 % of the patients and isolated skip metastasis
at level IV in 1.5 % of the patients. The risk factors associated with the lymph
node metastasis on univariete analysis were; higher grade, tumor size >1 cm and
tumor thickness >3 mm. On multivariate analysis only the tumor thickness was
found to be a risk factor for the lymph node metastasis (hazard ratio of 21.59).
CONCLUSIONS: T1 sqamous cell carcinoma of tongue is associated with a high
incidence of lymph node metastasis. Elective neck dissection should be considered
in all patients with tumors more than 3 mm in thickness.
PMID- 25114463
TI - Clinical Outcomes in the Google Era: The PB Desai Oration, ASICON 2013.
AB - This article is based upon the PB Desai Oration which was given by the author in
Ahmedabad on 28th December 2013 at the National Congress of the Association of
Surgeons of India at the invitation of the Executive Board of the Indian
Association for Surgical Oncology.
PMID- 25114462
TI - The risk and pattern of pelvic and para aortic lymph nodal metastasis in patients
with intermediate and high risk endometrial cancer.
AB - There is a continuous debate about the extent and prognostic value of
retroperitoneal lymphadenectomy in endometrial cancer. Systematic pelvic and para
aortic lymphadenectomy in endometrial cancer provides a more accurate assessment
of neoplastic spread and may help in better individualization of patients for
adjuvant therapy. To evaluate the risk and pattern of retroperitoneal lymph nodes
metastasis in patients with endometrial cancers having intermediate and high risk
factors for nodal metastasis and recurrence. We conducted a prospective
nonrandomized study of 62 cases of high risk endometrial cancers examined and
treated at our regional cancer institute between the years 2008 and 2012. The
inclusion criteria: The intermediate risk; all patients having grade 3 or
undifferentiated adenocarcinomas with less than half MI and the grade 1, 2 tumors
having more than half MI with tumor size >2 cm. The high risk group; all the
patients having grade 3 or undifferentiated adenocarcinomas with more than half
MI, the grade 1, 2 tumors with lymph vascular space invasion (LVSI) or cervical
stromal invasion as depicted by pre-operative MRI. The type 2 histology uterine
papillary serous, clear cell and squamous cell carcinomas. The patients staging
was carried out according to the classification established by the FIGO for
endometrial cancer in 2009. The Chi-square test was used to analyze the
correlation between tumor grade, myometrial invasion, size of the lesion and
lymph nodes metastasis and Fisher's correction done whenever the frequency
distribution was less than five. The patients mean age was 58.3 (range 31 to 76
years). A total of 118 endometrial cancer patients were treated during the study
period. The 56 (47.5 %) patients belonged to low risk and 62 (52.5 %) patients
belonged to high risk endometrial cancers. The 52 of 62 cases were eligible for
the analysis. The 10 patients' were excluded from further analysis as the post
operative specimens final histopathologic examinations in nine cases revealed
carcinosarcoma uterus and one case with yolk sac tumor of endometrium. The total
17(32.7 %) of 52 cases had retroperitoneal nodes metastasis; nine of 17 (52.9 %)
in this group had both pelvic and para-aortic lymph nodal metastasis and one of
17 (5.9 %) had isolated para-aortic lymph nodal metastasis. The high grade tumors
(grade 3) revealed 41.4 % pelvic and 20.7 % para-aortic lymph nodes metastasis
and there was statistically significant higher nodal metastasis in both pelvic
and para-aortic lymph nodes with increasing depth of myometrial invasion (P =
0.0119 and P = 0.0001) and increasing size of the lesion. (P = 0.04 and P =
0.0501). The intermediate and high risk endometrial cancer is associated with
greater degree of lymph node metastasis. A complete surgical staging which
involves extrafascial hysterectomy or a type 3 radical hysterectomy when there is
a cervical involvement, along with bilateral salphingo-oophorectomy, pelvic, para
aortic lymphadenectomy and an omentectomy when indicated as in the present study,
is a valuable modality of treatment in intermediate and high risk cases of
endometrial cancers for determining the prognosis and appropriate categorization
of these women for adjuvant therapy. It is also possible to achieve a complete
surgical staging in these groups of women with acceptable morbidity when
performed by a trained gynaecologic oncologist.
PMID- 25114464
TI - Xeroderma pigmentosum: clinicopathological review of the multiple oculocutaneous
malignancies and complications.
AB - Multiple oculo-cutaneous malignancies are a common manifestation on sun-exposed
facial areas in patients with Xeroderma pigmentosum (XP). Commonly seen are the
basal cell carcinoma and the squamous cell carcinomas which manifest in the early
first decade in contrast to fifth and sixth decade in the general population. XP
manifests as photosensitivity, hyperpigmentation, premature skin aging and
malignant changes like squamous cell carcinoma, basal cell carcinoma,
fibrosarcoma and rarely malignant melanoma as well as internal malignancies. We
report 11 cases of Xeroderma pigmentosa managed in our institute which included
sex males and five females. All had photosensitivity, hyperpigmentation and
consanguinity with facial malignant lesions like SCC and BCC. Ocular signs of
photophobia and excessive lacrimation was seen in all the cases while blurring of
vision due to corneal clouding, corneal injection, pterygium and limbal SCC were
seen in 5 cases. SCC of the lids were seen in 7 cases while BCC seen in 8 cases
and limbal and conjunctival SCC seen in one case. All were managed with excision
while one case of melanoma with neck secondaries needed radical neck dissection
while the other orbital exenteration. Oculo-cutaneous malignancies occur in the
sun exposed areas so patients are advised regular follow up with speciality care.
Awareness about the rare condition and importance of early detection and
prevention of UV rays induced skin damage should be propagated. The disease is
ultimately fatal, life can be prolonged by simple preventive measures to minimize
sun exposure and early detection of the skin lesions and management.
PMID- 25114465
TI - Virtual reality surgical simulators- a prerequisite for robotic surgery.
AB - The field of computer assisted minimally invasive surgery is rapidly expanding
worldwide, including in India. With more hospitals in India contemplating the
acquisition of a robotic platform, training of robotic surgeons is becoming
essential. Virtual reality simulators can be used for surgeons to become
acquainted with the robotic console prior to live surgery. Our aim was to
evaluate the amount of simulator training required before a surgeon first
operates on the da Vinci(r) Surgical System. Simulations were conducted on the
Intuitive Surgical's da Vinci(r) Robot Skill Simulator using the software
obtained from Mimic Technologies. Participants included attending staff surgeons
experienced in robotic surgery and novices. A set of seven activities were chosen
for each participant. Based on the mean exercise score from the first attempt,
staff surgeons outperformed the novices in all exercises. However, the difference
in score between the staff and the novices decreased after the participants
repeated the exercises and by the sixth attempt most of the novices obtained
similar scores to the staff, suggesting that this might be at present the minimum
set of repetitions indicated (or required) prior to performing life robotic
surgery.
PMID- 25114466
TI - Chondroradionecrosis of larynx a delayed complication of radiotherapy: management
and review of literature.
AB - Background/objectives Chondroradionecrosis (CRN) of the larynx is a rare and
grave complication of radiotherapy which can be fatal if not managed
aggressively. A recent trend towards organ preservation protocols towards even
advanced stage laryngeal malignancies and with further advances in terms of
technology and safety radiation as external beam and intensity modulated
varieties are preferred for certain stages of squamous cell carcinomas. Materials
and methods We are reporting a series of 4 cases of CRN of the larynx treated in
our hospital with 3 cases of stage III carcinoma glottis and one stage III
carcinoma supraglottis with no nodal metastasis. One glottis cancer had 2
sittings of laser microlaryngeal excision earlier. All were in grade 4 CRN and
one improved with medical line and HBO and the other 3 progressed and salvage
laryngectomy and pectoralis major myocutaneous flap to cover the fistulous skin
defect was grafted. CONCLUSION: Laryngeal CRN being a rare and intensely morbid
complication of radiotherapy should be suspected and diagnosed at the earliest by
endoscopic and imaging methods. Disease progression and chances of tumor
recurrence should be followed up with PET CT and a call on salvage laryngectomy
with repair of the anterior neck defects with non irradiated musculocutaneous
flaps or vascularised tissue transfer should be promptly taken.
PMID- 25114468
TI - Intussusception of a small bowel large B-cell lymphoma.
AB - Gastrointestinal tumors can rarely cause intestinal intussusception. Herein, we
describe a 74 year-old male with a presumed diagnosis of Crohn's disease who
presented with persistent symptoms refractory to medical management. Radiography
demonstrated small bowel intussusception into the cecum. Lower endoscopy with
biopsy diagnosed small bowel large Bcell lymphoma. Management included
laparoscopic ileocecectomy and adjuvant R-CHOP chemotherapy. Long term outcomes
of small bowel large B-cell lymphoma are related to disease stage at diagnosis,
and average close to 75 %.
PMID- 25114469
TI - p53: Revealing the Unusual Suspect: a Study and Field Cancerization Minireview.
PMID- 25114467
TI - Chemotherapy and targeted therapy for gall bladder cancer.
AB - Gall bladder cancer is a common cancer in the Ganges belt of North-eastern India.
In view of incidental diagnosis of gall bladder cancer by physicians and
surgeons, the treatment is not optimised. Most patients present in advanced
stages and surgery remains the only option to cure. This review highlights the
current evidence in advances in systemic therapy of gall bladder cancer.
PMID- 25114470
TI - The aesthetic and oncological challenges in the management of an atypical nodular
hidradenoma of the pinna.
AB - Nodular hidradenomas are benign adenomatous tumours of sweat gland origin, which
commonly arise from the skin of the head, neck and extremities. Some of these
benign appearing lesions exhibit aggressive clinical behaviour with rapid growth,
pigmentation and ulceration. These tumors are designated as "atypical nodular
hidradenomas" and are known to histologically possess some focal atypical
features i.e. nuclear pleomorphism, focal necrosis or prominent mitotic activity.
Nodular hidradenomas involving the pinna are rare and to the best of our
knowledge there have been no prior reports in the English language literature. We
describe a unique case of a 45-year-old woman with an atypical nodular
hidradenoma of the left pinna and discuss the aesthetic and the oncological
issues pertaining to the reconstruction of the pinna.
PMID- 25114471
TI - Pleomorphic adenoma of breast-a case report and review of literature.
AB - Pleomorphic adenoma (PA) is a rare benign tumour of the breast. However
inadequate surgery of this tumour, which is notorious for its pseudopod like
extension into adjacent tissue, results in recurrence. We report a case of
pleomorphic adenoma of the breast that has been excised at a local hospital and
then referred to a tertiary care hospital for definite management. The diagnostic
dilemmas and optimal management, of such cases where dependable pathology report
and details of primary surgery are often not available, are discussed.
PMID- 25114472
TI - Primary angiosarcoma of breast: a case report.
AB - Primary breast sarcomas are rare entities. These malignant tumors originate from
mesenchymal glandular breast tissue and account for <1 % of all breast cancer
cases. Angiosarcomas are rare malignant tumors that arise from endothelial cells
lining vascular channels. Most angiosarcomas are secondary to radiotherapy
treatments for breast cancer or to an arm lymphoedema subsequent to a modified
radical mastectomy. Primary angiosarcomas are rare and account for 0.04 % of all
malignant breast tumors.
PMID- 25114473
TI - Aneurysmal bone cyst of medial end of clavicle in a child, a rare case report.
AB - Aneurysmal bone cyst is a locally aggressive benign tumor accounting for 3 % of
all benign bone tumors. It most commonly arises from ends of long bones and
relatively rare in flat bones. Clavicle is a very rare site for bone tumors with
secondaries more common than primaries. Very few cases of aneurysmal bone cyst
have been reported in literature. We hereby report interesting and a rare case of
aneurysmal bone cyst of medial end of clavicle in a eight year old lady which was
treated with extended curettage and calcium sulfate bone grafting.
PMID- 25114474
TI - Steatohepatitic hepatocellular carcinoma-a case report with literature review.
AB - We report a case of a 65 year old male who presented with complaints of pain
right upper abdomen for past 3 months. He was a known diabetic and hypertensive.
On evaluation he was found to have space occupying lesion in the right lobe of
the liver. USG Guided FNC done showed a Hepatocellular Carcinoma with predominant
steatosis. He underwent Right Hepetectomy for the same and Histopathological
examination revealed a Steatohepatitic Hepatocellular Carcinoma with background
liver showing minimal steatosis and no significant fibrosis. This case is
reported to provide better insight into the understanding of pathophysiology of
metabolic syndrome as an etiological agent for development of HCC.
PMID- 25114475
TI - Right hepatectomy in icteric type hepatocellular carcinoma-report of a case and
literature review.
PMID- 25114476
TI - Recent research about mild cognitive impairment in China.
AB - The rapid aging of the Chinese population has spurred interest in research about
the cause and prevention of dementia and its precursor, mild cognitive impairment
(MCI). This review summarizes the last decade of research in China about MCI.
Extensive research about the epidemiology, neuropsychological characteristics,
diagnosis, genetic etiology, neuroimaging and electrophysiological changes, and
treatment of MCI has provided some new insights but few breakthroughs. Further
advances in the prevention and treatment of MCI will require a greater emphasis
on multi-disciplinary prospective studies with large, representative samples that
use standardized methods to assess and monitor changes in cognitive functioning
over time.
PMID- 25114477
TI - Randomized controlled trial of four protocols of repetitive transcranial magnetic
stimulation for treating the negative symptoms of schizophrenia.
AB - BACKGROUND: The negative symptoms of schizophrenia are not effectively treated
with antipsychotic medications. Repetitive transcranial magnetic stimulation
(rTMS) is an alternative approach that may be more effective in treating negative
symptoms, but there has been little research comparing the effectiveness of
different rTMS stimulation protocols. OBJECTIVE: Compare the effect of four
different rTMS protocols in the treatment of the negative symptoms of
schizophrenia. METHODS: Ninety-six patients with schizophrenia who had prominent
negative symptoms were randomly assigned to four treatment groups: 10 Hz, 20 Hz,
theta burst stimulation (TBS), and mock rTMS (i.e., the control group). In the
first three groups, the left dorsolateral prefrontal cortex was stimulated at 80%
of the motor threshold five times per week for four weeks. Before and after the
treatment, evaluators who were blind to the group assignment of patients
administered the Positive and Negative Syndrome Scale (PANSS), the Scale for the
Assessment of Negative Symptoms (SANS) and the Treatment Emergent Symptom Scale
(TESS). RESULTS: Three of the 96 patients dropped out during the trial (two from
the control group and one from the 20 Hz group). Compared to the control group,
after 4 weeks of rTMS treatment all three treatment groups had lower scores on
the PANSS negative symptom subscale, the PANSS general psychopathology subscale,
and the SANS. The TBS group had significantly larger reductions in these scores
than the 10 Hz group and the 20 Hz group, but there were no significant
differences between the 10 Hz and 20 Hz groups. There were no pre- versus post
treatment differences in the PANSS positive symptom subscale scores between the
four groups. No serious adverse events occurred and there were no statistically
significant differences in the TESS scores across the four groups. CONCLUSIONS:
We find that rTMS, particularly the TBS stimulation protocol for rTMS, is a safe
and effective treatment method for patients with schizophrenia who have prominent
negative symptoms. Longitudinal studies with large samples are needed to optimize
the rTMS treatment, to identify the stimulation protocol, duration, intensity and
treatment interval that provides the best therapeutic result at the lowest risk
to the patient.
PMID- 25114478
TI - Cross-sectional survey of the relationship of symptomatology, disability and
family burden among patients with schizophrenia in Sichuan, China.
AB - BACKGROUND: Schizophrenia is a chronic condition that leads to high rates of
disability and high levels of family burden but the interactive relationship
between these variables remains unclear, particularly in low- and middle-income
countries where the vast majority of patients live with their families. AIM:
Assess the symptom severity, level of disability, and family burden among
clinically stable outpatients with schizophrenia in Sichuan, China. METHODS: A
total of 101 clinically stable outpatients with schizophrenia who had a median
duration of illness of five years were assessed using the World Health
Organization Disability Assessment Scale 2.0 (WHODAS II), the Positive and
Negative Syndrome Scale (PANSS) and the Family Adaptation, Partnership, Growth,
Affection and Resolve Index scale (APGAR); and their caregivers were surveyed
using the Family Burden Interview Schedule (FBIS). RESULTS: Among the 101
patients, 92 lived with their immediate family members, 74 had clinically
significant disability, and 73 were unemployed. The level of disability was
associated with the severity of symptoms (r=0.50, p<0.001), duration of illnesses
(r=0.22, p=0.028), age of onset (r=-0.22, p=0.024) and patients' level of
satisfaction with family support (r=-0.30, p=0.020). Disability was also
associated with the overall level of family burden (r=0.40, p<0.001), and with
several subtypes of family burden: financial burden (r=0.21, p=0.040), the degree
of disruption in family routines (r=0.33, p=0.001), the effect on family leisure
activities (r=0.31, p=0.001) and the quality of family interactions (r=0.43, p<
0.001). Four variables remained significantly associated with the level of
disability in the stepwise multivariate linear regression: duration of illness,
severity of symptoms, patient satisfaction with family support, and the overall
burden of the illness on the family. CONCLUSIONS: Even after adjusting for the
severity of patients' symptoms, patient disability is independently associated
with family burden. This highlights the importance of targeting both symptoms and
disability in treatment strategies for this severe, often lifelong, condition. In
countries like China where most individuals with schizophrenia live with their
families, family burden is an important component of the impact of the illness on
the community that should be included in measures of the relative social and
economic importance of the condition.
PMID- 25114479
TI - Five-year follow-up study of multi-domain cognitive training for healthy elderly
community members.
AB - BACKGROUND: Cognitive training, a safe non-pharmacological intervention, may help
mitigate cognitive decline and prevent the development of dementia in elderly
individuals. OBJECTIVE: Evaluate the long-term effects of cognitive training
among healthy elderly community members. METHODS: Healthy individuals 70 years of
age or older from one urban community in Shanghai were screened and the 151
individuals who met inclusion criteria were assigned either to an intervention
group (n=90) or a control group (n=61). The intervention involved twice-weekly
training in reasoning, memory, and strategy that continued for 12 weeks (a total
of 24 sessions). Participants were assessed at baseline and at 12 weeks, and 5
years after enrollment using the Chinese versions of the Neuropsychological Test
Battery for Elderly persons (NTBE), the Stroop Color-Word Test, and a general
health questionnaire. RESULTS: Forty-nine (54%) intervention group subjects and
33 (54%) control group subjects completed the 5-year follow-up. There were few
differences in the baseline neurocognitive measures of those who did and did not
complete the 5-year follow-up, and there were few differences between those who
dropped out of the intervention group compared to those who dropped out of the
control group. At the 5-year follow-up, individuals in the intervention group
performed better than those in the control group on only 5 measures (in the
Trails Making A Test and the Cancellation Test 3) of the 61 measures assessed by
NTBE and the Stroop tests, but none of these differences met the pre-determined
required level of statistical significance (p=0.0008). CONCLUSION: We do not
confirm the results of previous studies that report long-term benefits of brief
cognitive training courses for elderly community residents. Our failure to
identify differences in cognitive functioning five years after cognitive training
is not likely due to differential dropout between the intervention and control
groups but may be related to the relatively small sample and the large number of
measures being assessed. Future intervention studies for cognitive training in
the elderly should be hypothesis driven (i.e., focused on a single outcome
measure of interest), use much larger samples, and include regular booster
sessions as part of the cognitive training package.
PMID- 25114481
TI - Challenges in the diagnosis and treatment of transsexualism in contemporary
China.
PMID- 25114480
TI - Duration of untreated psychosis and clinical outcomes of first-episode
schizophrenia: a 4-year follow-up study.
AB - BACKGROUND: The relationship between the duration of untreated psychosis and long
term clinical outcomes remains uncertain. OBJECTIVE: Prospectively assess the
relationship of the duration of untreated psychosis on clinical outcomes in a
sample of individuals with first-onset schizophrenia treated at the Pudong Mental
Health Center from January 2007 to December 2008. METHODS: Information about
general health, psychotic symptoms and social functioning were collected using
the Brief Psychiatric Rating Scale (BPRS), Treatment Emergent Symptom Scale
(TESS), Morningside Rehabilitation Status Scale (MRSS), and Social Disability
Screening Schedule (SDSS) at baseline and in June 2010 and June 2012. RESULTS:
The 43 individuals with first-episode schizophrenia participating in the study
were divided into short (<24 weeks) and long (>24weeks) duration of untreated
psychosis (DUP) groups. The mean (sd) duration of follow-up was 1197 (401) days
in the short DUP group and 1412 (306) days in the long DUP group (t=9.98,
p=0.055). Despite less prominent psychotic symptoms at the time of first
diagnosis among patients who had a long DUP compared to those with a short DUP
(BPRS mean scores, 42.5 [8.4] v. 50.0 [10.6], t=2.42, p=0.0210) and a similar
number of clinical relapses (based on positive symptoms assessed by the BPRS),
patients with a long DUP were more likely to require hospitalization at the time
of first diagnosis (52% [11/21] v. 9% [2/22], chi(2) =9.55, p=0.002) and more
likely to require re-hospitalization during the first two years of treatment (67%
[14/21] v. 32% [7/22], chi(2) =5.22, p=0.022). Moreover, after four years of
routine treatment, despite a similar severity of positive symptoms, patients who
had had a long DUP prior to initiating treatment had significantly poorer social
functioning than those who had had a short DUP (SDSS mean scores, 7.0 [5.2] v.
3.4 [4.9], t=2.20, p=0.035). CONCLUSIONS: These findings show that despite having
a similar level of psychotic symptoms - as measured by the BPRS - compared to
patients with a short DUP, patients with schizophrenia who have a long DUP prior
to initial treatment have poorer long-term social functioning. This confirms the
clinical importance of the early recognition and treatment of individuals with
chronic psychotic conditions.
PMID- 25114482
TI - Case report of refractory tardive dystonia induced by olanzapine.
AB - SUMMARY: Tardive dystonia (TDt), a cluster of extrapyramidal symptoms that are
caused by long-term use of antipsychotic medication, is characterized by
difficulty in autonomic movements of skeletal (voluntary) muscles and consequent
deformations of the body. TDt is rarely seen among patients taking olanzapine,
but olanzapine was the precipitating antipsychotic medication in this 22-year old
male patient with schizophrenia who developed lip puckering, persistent
involuntary torticollis, muscular pain, axial dystonia and unstable gait after
taking a standard dose of olanzapine regularly for about one year. His symptoms
did not resolve after his olanzapine was stopped. Four months of treatment with
clozapine combined with magnesium valproate, vitamin E, tiapride, and lorazepam
did not lead to any improvement in the dystonia.
PMID- 25114484
TI - Report on the Shanghai Conference of the ICD-11 Field Studies Coordinating Group.
PMID- 25114483
TI - Establishing a data monitoring committee for clinical trials.
AB - SUMMARY: A data monitoring committee (DMC) is a group of clinicians and
biostatisticians appointed by study sponsors who provide independent assessment
of the safety, scientific validity and integrity of clinical trials. In the
United States, the Food and Drug Administration requires the formation of DMC in
all trials that assess new interventions. DMC are also strongly recommended in
other clinical studies that have substantial safety issues, that have double
blind treatment assignment or that are expected to have a major impact on
clinical practice. They are important in clinical research in psychiatry because
they provide an added layer of protection for the vulnerable populations that are
often enrolled in such studies. This report describes the role, formation and
operation of DMC.
PMID- 25114485
TI - Neuroimaging studies of depressive disorders in China since 2000.
AB - SUMMARY: This paper reviews neuroimaging studies of depressive disorders
conducted in Chinese populations since 2000. Both cross-sectional and
longitudinal studies using structural and functional imaging techniques have
compared different types of depressed individuals, with and without specific
genotypes, and the characteristics of depressed individuals before and after
treatment with antidepressants. Many of the findings are unstable - probably
because most of the studies are underpowered - but there have been some important
contributions to the international literature. Future studies in China need to
use standardized methods, longitudinal designs, and joint application of both
structural and functional MRI.
PMID- 25114487
TI - Changes in behavior and in brain glucose metabolism in rats after nine weeks on a
high fat diet: a randomized controlled trial.
AB - BACKGROUND: A high-fat diet (HFD) is a well-known risk factor for cardio
cerebrovascular disease but the relationship between a HFD and depressive
symptoms remains unknown. OBJECTIVE: Compare changes in behavioral and measures
of brain glucose metabolism in rats fed a HFD to those of rats fed a standard
diet. METHODS: Twenty male Sprague-Dawley rats were randomly assigned to a study
group (n=10) that received a high fat diet for 9 weeks or a control group (n=10)
that received a standard diet for 9 weeks. At baseline and at the end of the 9
week trial assessments included body weight, serum lipids (total cholesterol,
triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein
cholesterol), the sucrose preference test, and the open field test. The rate of
brain glucose metabolism in different brain regions (assessed using micro
positron emission tomography) at the end of the trial was also compared between
the two groups of rats. RESULTS: Nine weeks of a HFD in rats resulted in the
expected increase in weight and changes in serum lipid levels, but it was also
associated with a decreased preference for sucrose (which may be due to a loss of
interest in pleasurable activities), increased weight-adjusted water intake, and
a significant deactivation of the right thalamus and right striatum (based on
decreased rates of glucose metabolism). In the HFD group the magnitude of the
drop in the sucrose preference was strongly correlated to the magnitude of the
deactivation of the right thalamus (r=0.78) and the right striatum (r=0.81).
CONCLUSIONS: These findings support hypotheses about the role of a HFD in the
causal pathway for depressive symptoms. Further work is needed to clarify the
underling mechanism, but it appears that the interaction between the content of
the diet and the limbic system-striatum-thalamus circuit plays a role in both
eating behavior and depressive symptoms.
PMID- 25114486
TI - Two-year prospective case-controlled study of a case management program for
community-dwelling individuals with schizophrenia.
AB - BACKGROUND: A community-based rehabilitation program is an essential element of
the comprehensive treatment of individuals with schizophrenia. OBJECTIVE: Assess
the long-term effects of a community-based case management program for providing
rehabilitations services to individuals with schizophrenia. METHODS: A total of
730 community-residing participants who met ICD-10 diagnostic criteriafor
schizophrenia were enrolled, 380 in the case management group and 350 in the
control group from two districts in Shanghai. Case management involved monthly
training visits with patients and their co-resident family members that focused
on encouraging medication adherence. Participants were assessed every three
months for 24 months with the Camberwell Assessment of Need (CAN), Positive and
Negative Syndrome Scale (PANSS), WHO-Disability Assessment Scale (WHO-DAS), and
the Quality of Life Scale (QOLS). Level of discomfort due to side-effects was
also assessed every three months. Individuals who discontinued their
antipsychotic medication without physician approval for one month or longer at
any time during follow-up were classified as 'self-determined medication
discontinuation'. RESULTS: Compared to the treatment as usual group (i.e., follow
up management every 3 months), by the end of the two-year follow-up those who
participated in the case management program had significantly lower rates of
medication discontinuation, significantly less severe negative symptoms, lower
relapse rates and lower rehospitalization rates. Other factors that had an
independent effect on discontinuation of medication included educational level
(those with more education had higher discontinuation rates), lack of family
supervision of medication, higher dosages of medication, and greater medication
related discomfort. CONCLUSIONS: Case management is a feasible and effective long
term method for improving the rehabilitation outcomes of community residents with
schizophrenia. Our results highlight the need to involve family members in the
management of patients' medication, to use the minimum effective dosage of
medication, and to aggressively manage all side-effects.
PMID- 25114488
TI - Retrospective assessment of factors associated with readmission in a large
psychiatric hospital in Guangzhou, China.
AB - BACKGROUND: Most psychiatric inpatients in China are involuntarily admitted by
their families, resulting in relatively long admissions and relatively low
readmission rates. However, this pattern may change after implementation of
China's new national mental health law (promulgated in 2013), which restricts
involuntary psychiatric admissions to the small proportion of mentally ill
individuals who are a danger to self or others. AIM: Assess the factors
associated with readmission rates of psychiatric inpatients in Guangzhou, China.
METHODS: A retrospective analysis of data from the Guangzhou Psychiatric
Hospital, one of the largest psychiatric hospitals in China, used Cox regression
models to evaluate the relationship between age, gender, diagnosis, marital
status, employment status, relationship with the primary caregiver, type of
medical insurance, length of stay of the index admission, and the number of
previous admissions to estimate the risk of readmission over the year following
discharge. Multivariate regression is used to assess factors associated with the
total time of readmission during the year of follow-up. RESULTS: Among 3455
patients admitted from 1 January 2011 to 31 December 2012 who had a mean (sd)
length of stay of 65.7 (66.3) days, 476 (13.8%) were readmitted one or more times
within one year of discharge. After considering all potential predictors of
readmission in a multivariate survival analysis, the number of previous
hospitalizations prior to the index admission was the only statistically
significant predictor of readmission. The only factor that was significantly
related to the total time of readmission was the duration of the index admission.
CONCLUSION: Shorter length of stay was not associated with increased readmission
rates in patients admitted to a large public psychiatric hospital in southern
China. This suggests that the expected decrease in the length of psychiatric
inpatient admissions that is likely to occur when, based on China's new
regulations, most patients are admitted voluntarily may not lead to increased
rates of readmission. Prospective studies with a more comprehensive set of
outcome measures (including patient functioning, medication adherence, and family
burden) are needed to monitor the effect of the law on patients and on the
distribution of mental health services.
PMID- 25114489
TI - Retrospective assessment of the prevalence of cardiovascular risk factors among
homeless individuals with schizophrenia in Shanghai.
AB - BACKGROUND: Cardiovascular diseases are increasingly important in China, but the
prevalence of risk factors for cardiovascular diseases in the indigent mentally
ill are unknown. AIM: Assess the prevalence of four key risk factors for
cardiovascular disease -- hypertension, hyperglycemia, hyperlipidemia and smoking
- among homeless patients with schizophrenia and identify factors associated with
the presence of these risk factors. METHODS: We reviewed medical charts of 181
homeless and 181 non-homeless patients with schizophrenia or schizophreniform
disorder admitted to the Shanghai Jiading Mental Health Center between May 2007
and April 2013. Demographic characteristics and risk factors of cardiovascular
events were compared between the two groups. Logistic regression models
identified the factors that were associated with the presence of one or more of
the four risk factors. RESULTS: The prevalence of hypertension and hyperlipidemia
were 19 to 20% in both males and females in the two groups; these rates are
similar to those reported in the general population. The prevalence of
hyperglycemia ranged from 11 to 15% among males and females in the two groups.
Smoking was highly prevalent in male patients (82% in homeless males and 78% in
non-homeless males) but, like in China generally, much less prevalent in female
patients (7% in homeless females and 5% in non-homeless females). The logistic
regression analysis found that male gender, older age, and urban (vs. rural)
residence were independently associated with the presence of one or more of the
four cardiovascular risk factors. Homelessness was not associated with the
presence of cardiovascular risk factors. CONCLUSION: This study is the first
known report on cardiovascular risk factors among homeless mentally ill in China.
The study did not assess several important factors (such as the type, dose and
duration of use of antipsychotic medication) but it was, nevertheless, able to
show that, unlike in high-income countries, homelessness is not related to
elevated risk of cardiovascular disease in Chinese individuals with mental
illnesses. Prospective studies with the growing number of homeless individuals in
China will be needed to get a clearer picture of the best ways to provide them
with the health care services they need.
PMID- 25114491
TI - Opportunities and challenges for promoting psychotherapy in contemporary China.
AB - China's first mental health law, which went into effect last year, envisages a
world in which psychotherapy is an integral part of all levels of medical care.
There are many obstacles to achieving this goal. The new law empowers
psychiatrists to provide psychotherapy but few of them have the time or
inclination to do so because of the lower incomes generated by non-biological
treatments. Trained clinical psychologists are in very short supply partly
because of the lack of supervised training opportunities and partly because the
current medical system - and the new mental health law - does not empower them to
diagnose or treat patients without the direct supervision of a physician.
Achieving the laudable goals of the new law will require substantial changes in
the regulations and, perhaps more importantly, in attitudes about the role and
status of psychologists within the medical care delivery system.
PMID- 25114492
TI - Case report of comorbid alcohol-induced psychotic disorder and Madelung's
disease.
AB - Madelung's disease, also known as benign symmetric lipomatosis (BSL), multiple
symmetric lipomatosis (MSL), fatty neck syndrome or Launois-Bensaude syndrome, is
a rare disease characterized by the presence of multiple, symmetric, loose
adipose tissues distributed around the neck, occipitalis, shoulder, back or
chest. The fat masses are non-encapsulated and therefore can move freely between
adjacent areas. This disease is most commonly seen among middle-aged Caucasian
men of Mediterranean origins; it is rarely reported in Asia. Among individuals
with Madelung's syndrome, 60 to 90% have a history of chronic alcohol abuse. We
report a case of a 51-year-old Chinese man with a history of alcohol use disorder
who had fat masses in his neck which gradually enlarged over a period of three
years. Based on the case history and the results of physical examination, neck CT
and other routine tests, he was diagnosed with Madelung's syndrome.
PMID- 25114494
TI - Item response theory for measurement validity.
AB - Item response theory (IRT) is an important method of assessing the validity of
measurement scales that is underutilized in the field of psychiatry. IRT
describes the relationship between a latent trait (e.g., the construct that the
scale proposes to assess), the properties of the items in the scale, and
respondents' answers to the individual items. This paper introduces the basic
premise, assumptions, and methods of IRT. To help explain these concepts we
generate a hypothetical scale using three items from a modified, binary (yes/no)
response version of the Center for Epidemiological Studies-Depression scale that
was administered to 19,399 respondents. We first conducted a factor analysis to
confirm the unidimensionality of the three items and then proceeded with Mplus
software to construct the 2-Parameter Logic (2-PL) IRT model of the data, a
method which allows for estimates of both item discrimination and item
difficulty. The utility of this information both for clinical purposes and for
scale construction purposes is discussed.
PMID- 25114493
TI - Use of diplotypes - matched haplotype pairs from homologous chromosomes - in gene
disease association studies.
AB - Alleles, genotypes and haplotypes (combinations of alleles) have been widely used
in gene-disease association studies. More recently, association studies using
diplotypes (haplotype pairs on homologous chromosomes) have become increasingly
common. This article reviews the rationale of the four types of association
analyses and discusses the situations in which diplotype-based analyses are more
powerful than the other types of association analyses. Haplotype-based
association analyses are more powerful than allele-based association analyses,
and diplotype-based association analyses are more powerful than genotype-based
analyses. In circumstances where there are no interaction effects between markers
and where the criteria for Hardy-Weinberg Equilibrium (HWE) are met, the larger
sample size and smaller degrees of freedom of allele-based and haplotype-based
association analyses make them more powerful than genotype-based and diplotype
based association analyses, respectively. However, under certain circumstances
diplotype-based analyses are more powerful than haplotype-based analysis.
PMID- 25114495
TI - Customized epithelial debridement for thin ectatic corneas undergoing corneal
cross-linking: epithelial island cross-linking technique.
AB - Thin corneas with a minimum corneal thickness less than 400 MUm after epithelial
removal represent a contraindication to standard epithelium-off cross-linking
(CXL) treatment due to a significant endothelial cell density decrease and
potentiality of permanent haze development. Preoperative swelling of the cornea
with hypoosmolar riboflavin solutions broadens the spectrum of CXL indications to
thin corneas. However the iatrogenic swelling effect might not be durable
throughout the CXL procedure increasing the risk of postoperative complications.
The transepithelial CXL technique proposed for thin corneas demonstrated poor
clinical results and mid- to long-term keratoconus instability. The epithelial
island CXL technique with customized pachymetry-guided epithelial debridement was
evaluated by means of in vivo laser scanning confocal microscopy, corneal
topography, and clinical examination in a 1-year follow-up, in order to assess if
it may be considered an alternative surgical option for keratoconic patients with
thin corneas undergoing corneal collagen CXL. According to our clinical and in
vivo micro-morphological results the technique results safe, and efficacious in
stabilizing progressive keratoconus and may be considered a valid option in the
treatment of thin ectatic corneas alone or in combination with hypoosmolar or
dextran-free riboflavin solutions.
PMID- 25114496
TI - Grader agreement, and sensitivity and specificity of digital photography in a
community optometry-based diabetic eye screening program.
AB - BACKGROUND: Digital retinal photography with mydriasis is the preferred modality
for diabetes eye screening. The purpose of this study was to evaluate agreement
in grading levels between primary and secondary graders and to calculate their
sensitivity and specificity for identifying sight-threatening disease in an
optometry-based retinopathy screening program. METHODS: This was a retrospective
study using data from 8,977 patients registered in the North Nottinghamshire
retinal screening program. In all cases, the ophthalmology diagnosis was used as
the arbitrator and considered to be the gold standard. Kappa statistics were used
to evaluate the level of agreement between graders. RESULTS: Agreement between
primary and secondary graders was 51.4% and 79.7% for detecting no retinopathy
(R0) and background retinopathy (R1), respectively. For preproliferative (R2) and
proliferative retinopathy (R3) at primary grading, agreement between the primary
and secondary grader was 100%. Where there was disagreement between the primary
and secondary grader for R1, only 2.6% (n=41) were upgraded by an
ophthalmologist. The sensitivity and specificity for detecting R3 was 78.2% and
98.1%, respectively. None of the patients upgraded from any level of retinopathy
to R3 required photocoagulation therapy. The observed kappa between the primary
and secondary grader was 0.3223 (95% confidence interval 0.2937-0.3509), ie, fair
agreement, and between the primary grader and ophthalmology for R3 was 0.5667
(95% confidence interval 0.4557-0.6123), ie, moderate agreement. CONCLUSION:
These data provide information on the safety of a community optometry-based
retinal screening program for screening as a primary and as a secondary grader.
The level of agreement between the primary and secondary grader at a higher level
of retinopathy (R2 and R3) was 100%. Sensitivity and specificity for R3 were
78.2% and 98.1%, respectively. None of the false-negative results required
photocoagulation therapy.
PMID- 25114497
TI - Intermittent acute angle closure glaucoma and chronic angle closure following
topiramate use with plateau iris configuration.
AB - This is a case report describing recurrent intermittent acute angle closure
episodes in the setting of topiramate use in a female suffering from migraines.
Despite laser peripheral iridotomy placement for the pupillary block component,
and the discontinuation of topiramate, the acute angle closure did not resolve in
the left eye with chronic angle closure and the patient required urgent
trabeculectomy. The right eye responded to laser peripheral iridotomy immediately
and further improved after the cessation of topiramate. While secondary angle
closure glaucoma due to topiramate use has been widely reported, its effects in
patients with underlying primary angle closure glaucoma have not been discussed.
Our report highlights the importance of recognizing the often multifactorial
etiology of angle closure glaucoma to help guide clinical management.
PMID- 25114498
TI - Learning curve of sutureless transconjunctival 20-gauge vitrectomy.
AB - BACKGROUND: To report the learning curve of transition from 20-gauge (20 G)
conventional vitrectomy to a 20 G sutureless vitrectomy technique. MATERIALS AND
METHODS: This is a retrospective descriptive case study of 32 eyes from 32
consecutive patients who underwent sutureless 20 G pars plana vitrectomy. A 20 G
microvitreoretinal blade was introduced, beveled transconjunctivally, slowly,
parallel with the limbus, creating a conjunctivoscleral tunnel incision. Study
participants were divided into three groups, and surgical time, induced
astigmatism, and complications were compared. RESULTS: Of 32 consecutive
patients, there was no significant difference in induced astigmatism or
maneuvering between the early learning curve and other groups. The true learning
curve was the first three patients. There were three cases where suturing the
sclerotomy was necessary: one port in each case, three of 32 cases (9.3%), or
three of 96 ports (2.9%). CONCLUSION: There were no significant difficulties in
surgical maneuvers while performing 20 g sutureless vitrectomy.
PMID- 25114500
TI - A case of retinopathy of prematurity treated by pattern scan laser
photocoagulation.
AB - We experienced a case of retinopathy of prematurity that was successfully treated
with pattern scan laser. Pattern scan laser treatment should be considered as one
treatment option for Retinopathy of Prematurity.
PMID- 25114499
TI - Relative sensitivity and specificity of 10-2 visual fields, multifocal
electroretinography, and spectral domain optical coherence tomography in
detecting hydroxychloroquine and chloroquine retinopathy.
AB - BACKGROUND: The purpose of this study was to determine the relative sensitivity
and specificity of 10-2 visual fields (10-2 VFs), multifocal electroretinography
(mfERG), and spectral domain optical coherence tomography (SD-OCT) in detecting
hydroxychloroquine retinopathy. METHODS: A total of 121 patients taking
hydroxychloroquine (n=119) or chloroquine (n=2) with 10-2 VF, mfERG, and SD-OCT
tests were retrospectively reviewed. Rates of test abnormality were determined.
RESULTS: Retinopathy was present in 14 and absent in 107. Eleven of 14 (78.6%)
patients with retinopathy were overdosed. Twelve (85.7%) had cumulative dosing
greater than 1,000 g. The sensitivities of 10-2 VF, mfERG, and SD-OCT in
detecting retinopathy were 85.7%, 92.9%, and 78.6%, respectively. The
specificities of 10-2 VF, mfERG, and SD-OCT in detecting retinopathy were 92.5%,
86.9%, and 98.1%, respectively. Positive predictive values of 10-2 VF, mfERG, and
SD-OCT in detecting retinopathy were less than 30% for all estimates of
hydroxychloroquine retinopathy prevalence. Negative predictive values were >99%
for all tests. CONCLUSION: Based on published estimates of hydroxychloroquine
retinopathy prevalence, all three tests are most reliable when negative, allowing
confident exclusion of retinopathy in patients taking <=6.5 mg/kg/day. Each test
is less useful in allowing a confident diagnosis of retinopathy when positive,
especially in patients taking <=6.5 mg/kg/day.
PMID- 25114501
TI - Comparison of Optomap ultrawide-field imaging versus slit-lamp biomicroscopy for
assessment of diabetic retinopathy in a real-life clinic.
AB - PURPOSE: We aimed to assess the agreement between clinical assessment of diabetic
retinopathy and Optomap ultrawide-field imaging (UWFI) in a real-life clinic
setting. METHODS: Structured examination findings, from diabetic patients
attending routine medical retina clinics in July 2011, were retrospectively
compared with the grade obtained from Optomap UWFI images, graded independently
by two ophthalmologists, taken at the same visit. RESULTS: A total of 84 eyes (42
patients) were examined, and 74 eyes (37 patients) were suitable for analysis.
The hospital Eye Service slit-lamp biomicroscopy grades for retinopathy were: no
diabetic retinopathy in zero eyes; background retinopathy in 21 eyes;
preproliferative retinopathy in 34 eyes; and proliferative retinopathy in 19
eyes. For retinopathy, the agreement between the Optomap UWFI and clinical
grading was moderate for both graders (kappa=0.57 and kappa=0.63), and there was
almost perfect agreement between the two graders (kappa=0.92). The clinical
grades for the presence of photocoagulation scars were: no photocoagulation scars
in 46 eyes and photocoagulation scars visible in 28 eyes, indicating substantial
agreement between the Optomap UWFI and clinical grading for both graders
(kappa=0.73 and kappa=0.64). There were two instances where proliferative
retinopathy was documented clinically but graded as preproliferative by both
graders of Optomap UWFI. These were investigated, and neither patient required
treatment, ie, the difference in retinopathy grade would not have affected the
patient outcomes. CONCLUSION: This study demonstrated moderate agreement between
Optomap UWFI and hospital slit-lamp biomicroscopy grading of patients'
retinopathy in a real-life medical retina clinic setting. The authors believe
that Optomap UWFI is, not only a very useful adjunct to clinical examination in
terms of detection and recording of retinopathy, but also, could have a role in
standalone "virtual" clinics.
PMID- 25114502
TI - Artificial tears potpourri: a literature review.
AB - Numerous brands and types of artificial tears are available on the market for the
treatment of dysfunctional tear syndrome. Past literature has focused on
comparing the components of these products on patient's clinical improvement. The
wide array of products on the market presents challenges to both clinicians and
patients when trying to choose between available tear replacement therapies.
Different formulations affect patients based on etiology and severity of disease.
In order to provide an unbiased comparison between available tear replacement
therapies, we conducted a literature review of existing studies and National
Institutes of Health clinical trials on commercially available, brand name
artificial tears. Outcomes evaluated in each study, as well as the percent of
patients showing clinical and symptomatic improvement, were analyzed. Fifty-one
studies evaluating different brands of artificial tears, and their efficacy were
identified. Out of the 51 studies, 18 were comparison studies testing brand name
artificial tears directly against each other. Nearly all formulations of
artificial tears provided significant benefit to patients with dysfunctional tear
syndrome, but some proved superior to others. From the study data, a recommended
treatment flowchart was derived.
PMID- 25114503
TI - Apoptosis and the FLIP and NF-kappa B proteins as pharmacodynamic criteria for
biosimilar TNF-alpha antagonists.
AB - Various criteria are necessary to assess the efficacy and safety of biological
medications in order to grant companies the right to register these medications
with the appropriate bodies that regulate their sale. The imminent expiration of
the patents on reference biological products which block the cytokine TNF-alpha
(tumor necrosis factor-alpha) raises the possibility of bringing so-called
biosimilars to the market (similar to the biologicals of reference products).
This occurrence is inevitable, but criteria to adequately evaluate these
medications are now needed. Even among controversy, there is a demand from
publications correlating the pro-apoptotic mechanism of the original TNF-alpha
antagonists (etanercept, infliximab, adalimumab, golimumab, and certolizumab
pegol) in the treatment of rheumatoid arthritis and other diseases. In this
article, the authors discuss the possibility of utilizing the pro-apoptotic
effect correlated with the regulation of the anti-apoptotic proteins FLIP and NF
kappaB as new criteria for analyzing the pharmacodynamics of possible biosimilar
TNF-alpha antagonists which should be submitted to regulatory agencies for
evaluation.
PMID- 25114504
TI - The load and release characteristics on a strong cationic ion-exchange fiber:
kinetics, thermodynamics, and influences.
AB - Ion-exchange fibers were different from conventional ion-exchange resins in their
non-cross-linked structure. The exchange was located on the surface of the
framework, and the transport resistance reduced significantly, which might mean
that the exchange is controlled by an ionic reaction instead of diffusion.
Therefore, this work aimed to investigate the load and release characteristics of
five model drugs with the strong cationic ion-exchange fiber ZB-1. Drugs were
loaded using a batch process and released in United States Pharmacopoeia (USP)
dissolution apparatus 2. Opposing exchange kinetics, suitable for the special
structure of the fiber, were developed for describing the exchange process with
the help of thermodynamics, which illustrated that the load was controlled by an
ionic reaction. The molecular weight was the most important factor to influence
the drug load and release rate. Strong alkalinity and rings in the molecular
structures made the affinity between the drug and fiber strong, while logP did
not cause any profound differences. The drug-fiber complexes exhibited sustained
release. Different kinds and concentrations of counter ions or different amounts
of drug-fiber complexes in the release medium affected the release behavior,
while the pH value was independent of it. The groundwork for in-depth exploration
and further application of ion-exchange fibers has been laid.
PMID- 25114505
TI - Pustular drug eruption due to Panax notoginseng saponins.
AB - Panax notoginseng saponins (PNS) are a patented product in the People's Republic
of China, and have extensive effects on the cardiovascular system. Here we report
on four elderly patients (one male and three female) with drug eruption induced
by PNS injection. All developed a sudden skin rash with pruritus from head to
foot, and subsequently accepted hospitalization. In each case, PNS had been used
for less than 1 week before appearance of the rash. No specific short-term
medications or changes in diet or exposure to environmental factors immediately
prior to appearance of the rash were identified. These four patients had some
interesting features in common, ie, pustules, fever, and elevated circulating
neutrophil counts, which required high-dose, long-term glucocorticoid therapy. To
our knowledge, this is the first report of pustular drug eruption induced by PNS
and provides a useful reference and warning for clinicians.
PMID- 25114506
TI - Evaluation of the biological activity of novel monocationic fluoroaryl-2,2'
bichalcophenes and their analogues.
AB - A series of bichalcophene fluorobenzamidines 5a-e was synthesized from the
corresponding mononitriles 4a-e via a direct reaction with lithium
bis(trimethylsilyl)amide LiN(TMS)2 followed by de-protection with ethanolic HCl
(gas). Bichalcophene fluorobenzonitriles 4a-e were prepared adopting a Stille
coupling reaction between the bromo compounds 3a-c and 2-(tri-n
butylstannyl)furan or analogues. As an approach to drug discovery, the structure
antimutagenicity relationship of novel fluoroarylbichalcophenes was examined
using the Ames Salmonella/microsomal assay. At nontoxic concentrations (10 and 20
MUM), all derivatives alone or in combination with sodium azide (NaN3; 2
MUg/plate) or benzo[a]pyrene (B[a]P; 20 MUM) in the presence of S9 mix were not
mutagenic. The fluoroaryl derivatives significantly reduced the NaN3-induced and
B[a]P-induced mutagenicity under pre-exposure and co-exposure conditions. The
recorded antimutagenic activity of fluoroaryl derivatives varied depending on the
kind of mutagen and the exposure regimen. Monocationic fluoroarylbichalcophenes
were superior to the corresponding mononitriles in reducing B[a]P-induced
mutagenicity. Nevertheless, mononitriles were more active against NaN3,
especially at low concentrations and under pre-exposure treatments. The
antimutagenic activity was congruent with a high antioxidant activity that could
promote the DNA repair system. The fluorine substitution changed the
antimutagenic signature of bichalcophenes. Some of these compounds could be
selected for further anticancer studies.
PMID- 25114507
TI - Novel artificial cell microencapsulation of a complex gliclazide-deoxycholic bile
acid formulation: a characterization study.
AB - Gliclazide (G) is an antidiabetic drug commonly used in type 2 diabetes. It has
extrapancreatic hypoglycemic effects, which makes it a good candidate in type 1
diabetes (T1D). In previous studies, we have shown that a gliclazide-bile acid
mixture exerted a hypoglycemic effect in a rat model of T1D. We have also shown
that a gliclazide-deoxycholic acid (G-DCA) mixture resulted in better G
permeation in vivo, but did not produce a hypoglycemic effect. In this study, we
aimed to develop a novel microencapsulated formulation of G-DCA with uniform
structure, which has the potential to enhance G pharmacokinetic and
pharmacodynamic effects in our rat model of T1D. We also aimed to examine the
effect that DCA will have when formulated with our new G microcapsules, in terms
of morphology, structure, and excipients' compatibility. Microencapsulation was
carried out using the Buchi-based microencapsulating system developed in our
laboratory. Using sodium alginate (SA) polymer, both formulations were prepared:
G-SA (control) at a ratio of 1:30, and G-DCA-SA (test) at a ratio of 1:3:30.
Complete characterization of microcapsules was carried out. The new G-DCA-SA
formulation was further optimized by the addition of DCA, exhibiting
pseudoplastic-thixotropic rheological characteristics. The size of microcapsules
remained similar after DCA addition, and these microcapsules showed no chemical
interactions between the excipients. This was supported further by the spectral
and microscopy studies, suggesting microcapsule stability. The new
microencapsulated formulation has good structural properties and may be useful
for the oral delivery of G in T1D.
PMID- 25114509
TI - Antimycobacterial, antimicrobial, and biocompatibility properties of para
aminosalicylic acid with zinc layered hydroxide and Zn/Al layered double
hydroxide nanocomposites.
AB - The treatment of tuberculosis by chemotherapy is complicated due to multiple drug
prescriptions, long treatment duration, and adverse side effects. We report here
for the first time an in vitro therapeutic effect of nanocomposites based on para
aminosalicylic acid with zinc layered hydroxide (PAS-ZLH) and zinc-aluminum
layered double hydroxides (PAS-Zn/Al LDH), against mycobacteria, Gram-positive
bacteria, and Gram-negative bacteria. The nanocomposites demonstrated good
antimycobacterial activity and were found to be effective in killing Gram
positive and Gram-negative bacteria. A biocompatibility study revealed good
biocompatibility of the PAS-ZLH nanocomposites against normal human MRC-5 lung
cells. The para-aminosalicylic acid loading was quantified with high-performance
liquid chromatography analysis. In summary, the present preliminary in vitro
studies are highly encouraging for further in vivo studies of PAS-ZLH and PAS
Zn/Al LDH nanocomposites to treat tuberculosis.
PMID- 25114508
TI - Potential roles of GPR120 and its agonists in the management of diabetes.
AB - Free fatty acids (FFAs) serve not only as nutrients that provide energy but also
as extracellular signaling molecules that manipulate intracellular physiological
events through FFA receptors (FFARs) such as FFAR4. FFAR4 is also known as G
protein coupled receptor 120 (GPR120). The main role of GPR120 is to elicit FFA
regulation on metabolism homeostasis. GPR120 agonism correlates with prevention
of the occurrence and development of metabolic disorders such as obesity and
diabetes. GPR120 activation directly or indirectly inhibits inflammation,
modulates hormone secretion from the gastrointestinal tract and pancreas, and
regulates lipid and/or glucose metabolism in adipose, liver, and muscle tissues,
which may help prevent obesity and diabetes. This review summarizes recent
advances in physiological roles of GPR120 in preventing insulin resistance and
protecting pancreatic islet function, and examines how resident GPR120 in the
pancreas may be involved in modulating pancreatic islet function.
PMID- 25114511
TI - Health state utilities associated with adult attention-deficit/hyperactivity
disorder.
AB - OBJECTIVES: With growing awareness of the importance of adult attention
deficit/hyperactivity disorder (ADHD) treatment, cost-effectiveness analyses,
including utilities, are needed to compare the value of treatment options.
Although utilities have been reported for childhood ADHD, little is known about
utilities representing adult ADHD. Therefore, the purpose of this study was to
estimate utilities associated with adult ADHD. METHODS: Health-state descriptions
of adult ADHD were drafted based on literature review, interviews with four
clinicians, and clinical trial data. Health states were revised based on a pilot
study with 26 participants. Final health states were rated in time trade-off
interviews with general population respondents in London and Edinburgh, UK.
RESULTS: A total of 158 participants completed interviews (mean age =47.0 years;
49.4% female; Edinburgh =80 participants). Mean (standard deviation [SD])
utilities were 0.82 (0.17), 0.68 (0.28), and 0.67 (0.28) for health states
describing treatment responders (health state A), nonresponders (health state B),
and untreated patients (health state C), respectively. Most participants rated
health state A as preferable to B (n=92; 58.2%) and C (n=97; 61.4%). The majority
rated B and C as equal (n=125; 79.1%). Paired Student's t-tests found that A had
a significantly greater mean utility than B (t=10.0; P<0.0001) and C (t=10.2;
P<0.0001). CONCLUSION: The current study provides utilities that may be used in
cost-utility models of treatment for adult ADHD. Results reflected clear
differences between health states representing treatment responders and
nonresponders/untreated patients. Current utilities were comparable to those
previously reported for childhood ADHD.
PMID- 25114510
TI - Clinical utility of erlotinib for the treatment of non-small-cell lung cancer in
Japanese patients: current evidence.
AB - Gefitinib, an epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI), has
been approved in Japan for the treatment of patients with advanced non-small-cell
lung cancer (NSCLC) based on Phase II clinical trials since 2002. Erlotinib,
another EGFR-TKI, was also approved a few years thereafter. In 2004, activating
mutations in the EGFR gene were discovered to be a predictive biomarker for EGFR
TKI treatment, and gefitinib, which is not effective for patients with EGFR wild
type NSCLC, has since been used only in patients with EGFR-mutated NSCLC. In
contrast, erlotinib is potentially effective for the treatment of EGFR wild-type
NSCLC. Similar to gefitinib, erlotinib is also effective for EGFR-mutated NSCLC
and has been used as an initial treatment for patients with advanced EGFR-mutated
NSCLC. Both gefitinib and erlotinib can be used in a Japanese clinical setting.
The approved daily dose of erlotinib (150 mg) is equal to the maximum tolerated
dose of erlotinib. In contrast, the daily dose of gefitinib has been set at 250
mg, which is approximately one-third of the maximum tolerated dose of gefitinib.
Accordingly, a higher serum concentration can be achieved using erlotinib,
compared with gefitinib. This advantage can be applied to the treatment of
central nervous system metastases (brain metastasis and carcinomatous
meningitis), the treatment of which is complicated by the difficulty drugs have
penetrating the blood-brain barrier. Although patients with EGFR-mutated NSCLC
respond dramatically to EGFR-TKIs, some patients have a poor response and the
majority eventually undergo disease progression. To overcome such resistance,
several novel treatment strategies, such as combination therapy and next
generation EGFR-TKIs, have been attempted.
PMID- 25114513
TI - Medication adherence: process for implementation.
AB - Improving medication adherence is a critically important, but often enigmatic
objective of patients, providers, and the overall health care system. Increasing
medication adherence has the potential to reduce health care costs while
improving care quality, patient satisfaction and health outcomes. While there are
a number of papers that describe the benefits of medication adherence in terms of
cost, safety, outcomes, or quality of life, there are limited reviews that
consider how best to seamlessly integrate tools and processes directed at
improving medication adherence. We will address processes for implementing
medication adherence interventions with the goal of better informing providers
and health care systems regarding the safe and effective use of medications.
PMID- 25114512
TI - What puts heart failure patients at risk for poor medication adherence?
AB - BACKGROUND: Medication nonadherence is a major cause of hospitalization in
patients with heart failure (HF), which contributes enormously to health care
costs. We previously found, using the World Health Organization adherence
dimensions, that condition and patient level factors predicted nonadherence in
HF. In this study, we assessed a wider variety of condition and patient factors
and interactions to improve our ability to identify those at risk for
hospitalization. MATERIALS AND METHODS: Medication adherence was measured
electronically over the course of 6 months, using the Medication Event Monitoring
System (MEMS). A total of 242 HF patients completed the study, and usable MEMS
data were available for 218 (90.1%). Participants were primarily white (68.3%),
male (64.2%), and retired (44.5%). Education ranged from 8-29 years (mean, 14.0
years; standard deviation, 2.9 years). Ages ranged from 30-89 years (mean, 62.8
years; standard deviation, 11.6 years). Analyses used adaptive methods based on
heuristic searches controlled by cross-validation scores. First, individual
patient adherence patterns over time were used to categorize patients in poor
versus better adherence types. Then, risk factors for poor adherence were
identified. Finally, an effective model for predicting poor adherence was
identified based on identified risk factors and possible pairwise interactions
between them. RESULTS: A total of 63 (28.9%) patients had poor adherence. Three
interaction risk factors for poor adherence were identified: a higher number of
comorbid conditions with a higher total number of daily medicines, older age with
poorer global sleep quality, and fewer months since diagnosis of HF with poorer
global sleep quality. Patients had between zero and three risk factors. The odds
for poor adherence increased by 2.6 times with a unit increase in the number of
risk factors (odds ratio, 2.62; 95% confidence interval, 1.78-3.86; P<0.001).
CONCLUSION: Newly diagnosed, older HF patients with comorbid conditions,
polypharmacy, and poor sleep are at risk for poor medication adherence.
Interventions addressing these specific barriers are needed.
PMID- 25114514
TI - Use of family member-based supervision in the management of patients with
hypertension in rural China.
AB - Medication nonadherence is a major problem in the management of hypertension. The
aim of this study was to develop a family member-based supportive therapy for
patients with hypertension to provide an affordable way to access essential
health services and to ensure adequate control of blood pressure. This study
applied a mixed methods approach using qualitative and quantitative study designs
in Yangzhong County, a rural area in the People's Republic of China. Findings
from indepth interviews demonstrated that the limited effects of traditional
health education, a lack of professional advice regarding antihypertensive
treatment, and age were related to a patient's adherence with regular blood
pressure measurement and taking medication. We also performed a quantitative
study, selecting two villages in Yangzhong County as study sites. A total of 188
patients with hypertension were invited to participate in a 6-month family member
based intervention trial. The primary outcomes were the acceptability and
feasibility of the intervention strategy. Secondary outcomes included medication
adherence and changes in blood pressure. More than 75% of patients expressed a
wish for external reminders, and 93.5% responded that they would accept the
family member-based supervision. The patients preferred their spouse or a child
as the supervisor. After the 6-month intervention, the proportion of patients
with uncontrolled blood pressure decreased from 87.2% to 45.7%. This pilot study
shows that external supervision by family members is acceptable and feasible for
patients with hypertension; it also shows favorable effects with regard to
improved treatment adherence and blood pressure control. Future randomized
controlled trials with modified intervention measures are needed to validate this
finding.
PMID- 25114515
TI - Peer-driven contraceptive choices and preferences for contraceptive methods among
students of tertiary educational institutions in Enugu, Nigeria.
AB - PURPOSE: To describe the methods preferred for contraception, evaluate
preferences and adherence to modern contraceptive methods, and determine the
factors associated with contraceptive choices among tertiary students in South
East Nigeria. METHODS: A questionnaire-based cross-sectional study of sexual
habits, knowledge of contraceptive methods, and patterns of contraceptive choices
among a pooled sample of unmarried students from the three largest tertiary
educational institutions in Enugu city, Nigeria was done. Statistical analysis
involved descriptive and inferential statistics at the 95% level of confidence.
RESULTS: A total of 313 unmarried students were studied (194 males; 119 females).
Their mean age was 22.5+/-5.1 years. Over 98% of males and 85% of females made
their contraceptive choices based on information from peers. Preferences for
contraceptive methods among female students were 49.2% for traditional methods of
contraception, 28% for modern methods, 10% for nonpharmacological agents, and 8%
for off-label drugs. Adherence to modern contraceptives among female students was
35%. Among male students, the preference for the male condom was 45.2% and the
adherence to condom use was 21.7%. Multivariate analysis showed that receiving
information from health personnel/media/workshops (odds ratio 9.54, 95%
confidence interval 3.5-26.3), health science-related course of study (odds ratio
3.5, 95% confidence interval 1.3-9.6), and previous sexual exposure prior to
university admission (odds ratio 3.48, 95% confidence interval 1.5-8.0) all
increased the likelihood of adherence to modern contraceptive methods.
CONCLUSION: An overwhelming reliance on peers for contraceptive information in
the context of poor knowledge of modern methods of contraception among young
people could have contributed to the low preferences and adherence to modern
contraceptive methods among students in tertiary educational institutions.
Programs to reduce risky sexual behavior among these students may need to focus
on increasing the content and adequacy of contraceptive information held by
people through regular health worker-led, on-campus workshops.
PMID- 25114516
TI - Relationship between cognitive impairment and apparent diffusion coefficient
values from magnetic resonance-diffusion weighted imaging in elderly hypertensive
patients.
AB - BACKGROUND: The purpose of this study was to determine a new method for the early
diagnosis and assessment of mild cognitive impairment in elderly individuals with
hypertension. Elderly hypertensive patients with cognitive impairment were
assessed by the Montreal Cognitive Assessment (MoCA) and Clinical Dementia Rating
Assessment (CDR). Cognitive results were compared to apparent diffusion
coefficient (ADC) values from magnetic resonance-diffusion weighted imaging.
METHODS: A total of 191 patients were categorized into four groups: a control
group (normal cognition and no hypertension; n=20); a normal group (hypertension
and normal cognition; n=33); an mild cognitive impairment group (n=80); and a
vascular dementia group (n=58). The MoCA and CDR tests were used to determine
cognition. ADC values in eight brain regions were calculated with magnetic
resonance-diffusion weighted imaging. Other characteristics were evaluated, eg,
blood pressure, MoCA, and CDR scores, and the comparisons of the four groups were
made. RESULTS: The MoCA and CDR scores differed among the four groups (P<0.001).
Systolic and diastolic blood pressure values increased as cognitive function
declined (P<0.001). Cognitive function declined as ADC values increased, and they
differed between elderly people with and without hypertension (P<0.001). Among
elderly hypertensive participants, ADC values were significantly increased in the
cortex and hippocampus. CONCLUSION: The MoCA and CDR tests were sufficiently
sensitive to evaluate cognition. Blood pressure was closely related to cognition,
as well as to functional and structural changes in the brain. These alterations
were evidenced through changes in the ADC values and were most obvious in the
cortex and hippocampus. Greater cognitive decline was observed in elderly
participants with hypertension compared to those without. As hypertensive stage
increased, greater ADC values were observed.
PMID- 25114517
TI - Subjective well-being in Swedish active seniors and its relationship with
physical activity and commonly available biomarkers.
AB - BACKGROUND: Physical activity is claimed to be related to well-being and to a
lower risk of cardiovascular disease. Therefore, the possible associations of
well-being with physical activity and biomarkers of somatic health were studied
in a sample of Swedish active seniors to determine the strength of these
associations. METHODS: Three hundred and eighty-nine community-dwelling senior
citizens (127 men and 262 women) of mean age 74 +/- 5 years were recruited for
this cross-sectional population study. Serum samples were analyzed for
lipoproteins and markers of inflammation. The Psychological General Well-Being
(PGWB) index was used to measure subjective well-being. Physical activity was
assessed by the International Physical Activity Questionnaire modified for the
elderly. RESULTS: More than 50% of men and women rated their physical activity as
high; in the women, there was a significant difference between the age groups
(younger and older than the median age [median =74.1 years], respectively). The
mean PGWB index indicates a high degree of subjective well-being in this group of
Swedish seniors. Of the PGWB subdimensions, general health had the strongest
positive relationship with physical activity (r (2)=5.4%). For the subdimensions
of depressed mood, positive well-being, vitality, and PGWB index, physical
activity had an r (2) <= 4%, while the contributions of sex, age, and biomarkers
were minor. CONCLUSION: We have estimated the contribution of physical activity
to the variance of subjective well-being in active seniors. Physical activity
appears to play a greater role as a determinant of subjective well-being than do
biomarkers of somatic health, especially in females, but most of the variance
remained unaccounted for by the studied variables.
PMID- 25114518
TI - Percutaneous coronary intervention in the elderly with ST-segment elevation
myocardial infarction.
AB - As a result of increased life expectancy, octogenarians constitute an increasing
proportion of patients admitted to hospital for ST-segment elevation myocardial
infarction (STEMI). Primary percutaneous coronary intervention is currently the
treatment of choice for octogenarians presenting with STEMI. The recent
literature on this topic has yielded controversial results, even though advances
in drug-eluting stents and new types of antithrombotic agents are improving the
management of STEMI and postoperative care. In this paper, we review the current
status of percutaneous coronary intervention in the elderly with STEMI, including
the reasons for their high mortality and morbidity, predictors of mortality, and
strategies to improve outcomes.
PMID- 25114519
TI - Interleukin-6 and interleukin-8 blood levels' poor association with the severity
and clinical profile of ex-smokers with COPD.
AB - BACKGROUND: The role of interleukins in the severity and clinical profile of
chronic obstructive pulmonary disease (COPD) is not known, but evidence supports
the contribution of systemic inflammation to disease pathophysiology. This study
evaluated the relationship of serum biomarkers to the severity and clinical
parameters of COPD. METHODS AND FINDINGS: Serum levels of high-sensitivity C
reactive protein, interleukin-6 (IL-6), and interleukin-8 (IL-8) were measured in
50 patients with stable COPD and in 16 controls. The levels of these biomarkers
were compared with parameters of severity, such as the grading of flow
obstruction using the recommendations of the Global initiative for chronic
Obstructive Lung Disease, the BMI (body mass index), obstruction, dyspnea,
exercise capacity (health index) index, the number of exacerbations within the
last year, and peripheral oxygen saturation after the six-minute walk test, and
with clinical parameters, such as bronchitis and non-bronchitis phenotypes, the
number of associated comorbidities, and the smoking burden. COPD patients
exhibited higher levels of IL-6 and IL-8 compared to the control group. Higher
levels of IL-6 occurred in COPD groups with body mass index <21 kg/m(2), with
more than two exacerbations in the past year, with a higher smoking burden, and
with bronchitis. The increase in serum IL-8 was found only in the group with the
highest number of exacerbations within the previous year. CONCLUSION: Increased
IL-6 was mainly associated with smoking burden, in patients who had smoked for
more than 30 pack-years and exhibited a bronchitis phenotype. No direct
association was observed for both IL-6 and IL-8 blood levels with the severity of
COPD in ex-smokers.
PMID- 25114520
TI - Pulmonary function impairment in patients with combined pulmonary fibrosis and
emphysema with and without airflow obstruction.
AB - BACKGROUND: The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is a
recently described entity associating upper-lobe emphysema and lower-lobe
fibrosis. We sought to evaluate differences in pulmonary function between CPFE
patients with and without airflow obstruction. SUBJECTS AND METHODS: Thirty-one
CPFE patients were divided into two groups according to the presence or absence
of irreversible airflow obstruction based on spirometry (forced expiratory volume
in 1 second/forced vital capacity <70% following inhalation of a beta2-agonist)
as follows: CPFE patients with airflow obstruction (CPFE OB(+) group, n=11), and
CPFE patients without airflow obstruction (CPFE OB(-) group, n=20). Pulmonary
function, including respiratory impedance evaluated using impulse oscillometry
and dynamic hyperinflation following metronome-paced incremental
hyperventilation, was retrospectively analyzed in comparison with that observed
in 49 chronic obstructive pulmonary disease (COPD) patients (n=49). RESULTS: In
imaging findings, low-attenuation-area scores on chest high-resolution computed
tomography, representing the degree of emphysema, were significantly lower in the
CPFE OB(-) group than in the CPFE OB(+) and COPD groups. In contrast, the
severity of pulmonary fibrosis was greater in the CPFE OB(-) group than in the
CPFE OB(+) group. In pulmonary function, lung hyperinflation was not apparent in
the CPFE OB(-) group. Impairment of diffusion capacity was severe in both the
CPFE OB(-) and CPFE OB(+) groups. Impulse oscillometry showed that respiratory
resistance was not apparent in the CPFE OB(-) group compared with the COPD group,
and that easy collapsibility of small airways during expiration of tidal breath
was not apparent in the CPFE OB(+) group compared with the COPD group. Dynamic
hyperinflation following metronome-paced incremental hyperventilation was
significantly greater in the COPD group than in the CPFE OB(-) group, and also
tended to be greater in the CPFE OB(+) group than in the CPFE OB(-) group.
CONCLUSION: The mechanisms underlying impairment of physiological function may
differ among CPFE OB(+) patients, CPFE OB(-) patients, and COPD patients. CPFE is
a heterogeneous disease, and may have distinct phenotypes physiologically and
radiologically.
PMID- 25114521
TI - Once-daily long-acting beta-agonists for chronic obstructive pulmonary disease:
an indirect comparison of olodaterol and indacaterol.
AB - PURPOSE: In the absence of head-to-head clinical trials comparing the once-daily,
long-acting beta2-agonists olodaterol and indacaterol for the treatment of
chronic obstructive pulmonary disease (COPD), an indirect treatment comparison by
systematic review and synthesis of the available clinical evidence was conducted.
METHODS: A systematic literature review of randomized, controlled clinical trials
in patients with COPD was performed to evaluate the efficacy and safety of
olodaterol and indacaterol. Network meta-analysis and adjusted indirect
comparison methods were employed to evaluate treatment efficacy, using outcomes
based on trough forced expiratory volume in 1 second (FEV1), Transition Dyspnea
Index, St George's Respiratory Questionnaire total score and response, rescue
medication use, and proportion of patients with exacerbations. RESULTS: Eighteen
trials were identified for meta-analysis (eight, olodaterol; ten, indacaterol).
Olodaterol trials included patients of all severities, whilst indacaterol trials
excluded patients with very severe COPD. Concomitant maintenance bronchodilator
use was allowed in most olodaterol trials, but not in indacaterol trials. When
similarly designed trials/data were analyzed for change from baseline in trough
FEV1 (liters), the following mean differences (95% confidence interval) were
observed: trials excluding concomitant bronchodilator: indacaterol 75 mcg versus
olodaterol 5 mcg, -0.005 (-0.077 to 0.067), and indacaterol 150 mcg versus
olodaterol 5 mcg, 0.020 (-0.036 to 0.077); trials with concomitant tiotropium:
indacaterol 150 mcg versus olodaterol 5 mcg, 0.000 (-0.043 to 0.042). In
sensitivity analyses of the full network, results for change from baseline in
trough FEV1 favored indacaterol, but this dataset suffered from trial design
heterogeneity. For the other endpoints investigated, no statistically significant
differences were found when analyzed in the full network. CONCLUSION: When
compared under similar trial conditions, olodaterol and indacaterol have similar
efficacy in patients with COPD. This research highlights the importance of
considering the concomitant COPD medication when evaluating treatment effects in
COPD.
PMID- 25114522
TI - Self-assembled nanoparticles based on the c(RGDfk) peptide for the delivery of
siRNA targeting the VEGFR2 gene for tumor therapy.
AB - The clinical application of small interfering RNA (siRNA) has been restricted by
their poor intracellular uptake, low serum stability, and inability to target
specific cells. During the last several decades, a great deal of effort has been
devoted to exploring materials for siRNA delivery. In this study, biodegradable,
tumor-targeted, self-assembled peptide nanoparticles consisting of cyclo(Arg-Gly
Asp-d-Phe-Lys)-8-amino-3,6-dioxaoctanoic acid-beta-maleimidopropionic acid
(hereafter referred to as RPM) were found to be an effective siRNA carrier both
in vitro and in vivo. The nanoparticles were characterized based on transmission
electron microscopy, circular dichroism spectra, and dynamic light scattering. In
vitro analyses showed that the RPM/VEGFR2-siRNA exhibited negligible cytotoxicity
and induced effective gene silencing. Delivery of the RPM/VEGFR2 (zebrafish)
siRNA into zebrafish embryos resulted in inhibition of neovascularization.
Administration of RPM/VEGFR2 (mouse)-siRNA to tumor-bearing nude mice led to a
significant inhibition of tumor growth, a marked reduction of vessels, and a down
regulation of VEGFR2 (messenger RNA and protein) in tumor tissue. Furthermore,
the levels of IFN-alpha, IFN-gamma, IL-12, and IL-6 in mouse serum, assayed via
enzyme-linked immunosorbent assay, did not indicate any immunogenicity of the
RPM/VEGFR2 (mouse)-siRNA in vivo. In conclusion, RPM may provide a safe and
effective delivery vector for the clinical application of siRNAs in tumor
therapy.
PMID- 25114524
TI - Investigation of the mechanism of enhanced skin penetration by ultradeformable
liposomes.
AB - This study aimed to determine the mechanism by which ultradeformable liposomes
(ULs) with terpenes enhance skin penetration for transdermal drug delivery of
fluorescein sodium, using transmission electron microscopy (TEM) and confocal
laser scanning microscopy (CLSM). Skin treated with ULs containing d-limonene,
obtained from in vitro skin penetration studies, was examined via TEM to
investigate the effect of ULs on ultrastructural changes of the skin, and to
evaluate the mechanism by which ULs enhance skin penetration. The receiver medium
collected was analyzed by TEM and CLSM to evaluate the mechanism of the drug
carrier system. Our findings revealed that ULs could enhance penetration by
denaturing intracellular keratin, degrading corneodesmosomes, and disrupting the
intercellular lipid arrangement in the stratum corneum. As inferred from the
presence of intact vesicles in the receiver medium, ULs are also able to act as a
drug carrier system. CLSM images showed that intact vesicles of ULs might
penetrate the skin via a transappendageal pathway, potentially a major route of
skin penetration.
PMID- 25114523
TI - Developments in human growth hormone preparations: sustained-release, prolonged
half-life, novel injection devices, and alternative delivery routes.
AB - Since the availability of recombinant human growth hormone (rhGH) enabled the
application of human growth hormone both in clinical and research use in the
1980s, millions of patients were prescribed a daily injection of rhGH, but
noncompliance rates were high. To address the problem of noncompliance, numerous
studies have been carried out, involving: sustained-release preparations,
prolonged half-life derivatives, new injectors that cause less pain, and other
noninvasive delivery methods such as intranasal, pulmonary and transdermal
deliveries. Some accomplishments have been made and launched already, such as the
Nutropin Depot microsphere and injectors (Zomajet, Serojet, and NordiFlex). Here,
we provide a review of the different technologies and illustrate the key points
of these studies to achieve an improved rhGH product.
PMID- 25114525
TI - Antibacterial properties of silver nanoparticles synthesized using Pulicaria
glutinosa plant extract as a green bioreductant.
AB - The antibacterial properties of nanoparticles (NPs) can be significantly enhanced
by increasing the wettability or solubility of NPs in aqueous medium. In this
study, we investigated the effects of the stabilizing agent on the solubility of
silver NPs and its subsequent effect on their antimicrobial activities. Silver
NPs were prepared using an aqueous solution of Pulicaria glutinosa plant extract
as bioreductant. The solution also acts as a capping ligand. During this study,
the antimicrobial activities of silver NPs, as well as the plant extract alone,
were tested against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus
aureus, and Micrococcus luteus. Silver NPs were prepared with various
concentrations of the plant extract to study its effect on antimicrobial
activity. Interestingly, various concentrations of P. glutinosa extract did not
show any effect on the growth of tested bacteria; however, a significant effect
on the antimicrobial property of plant extract capped silver NPs (Ag-NPs-PE) was
observed. For instance, the half maximal inhibitory concentration values were
found to decrease (from 4% to 21%) with the increasing concentrations of plant
extract used for the synthesis of Ag-NPs-PE. These results clearly indicate that
the addition of P. glutinosa extracts enhances the solubility of Ag-NPs-PE and,
hence, increases their toxicity against the tested microorganisms.
PMID- 25114526
TI - High gene delivery efficiency of alkylated low-molecular-weight polyethylenimine
through gemini surfactant-like effect.
AB - To our knowledge, the mechanism underlying the high transfection efficiency of
alkylated low-molecular-weight polyethylenimine (PEI) is not yet well understood.
In this work, we grafted branched PEI (molecular weight of 1,800 Da; bPEI1800)
with lauryl chains (C12), and found that bPEI1800-C12 was structurally similar to
gemini surfactant and could similarly assemble into micelle-like particles.
Stability, cellular uptake, and lysosome escape ability of bPEI1800-C12/DNA
polyplexes were all greatly enhanced after C12 grafting. bPEI1800-C12/DNA
polyplexes exhibited significantly higher transfection efficiency than
Lipofectamine 2000 in the presence of serum. Bioluminescence imaging showed that
systemic injection of bPEI1800-C12/DNA polyplexes resulted in intensive
luciferase expression in vivo and bioluminescence signals that could be detected
even in the head. Altogether, the high transfection efficacy of bPEI1800-C12 was
because bPEI1800-C12, being an analog of gemini surfactant, facilitated lysosome
escape and induced the coil-globule transition of DNA to assemble into a highly
organized micelle-like structure that showed high stability.
PMID- 25114527
TI - Hemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for
boron neutron capture therapy.
AB - The potential of boron-containing lipids with three different structures, which
were intended for use in boron neutron capture therapy, was investigated. All
three types of boron lipids contained the anionic dodecaborate cluster as the
headgroup. Their effects on two different tumor models in mice following
intravenous injection were tested; for this, liposomes with boron lipid,
distearoyl phosphatidylcholine, and cholesterol as helper lipids, and containing
a polyethylene glycol lipid for steric protection, were administered
intravenously into tumor-bearing mice (C3H mice for SCCVII squamous cell
carcinoma and BALB/c mice for CT26/WT colon carcinoma). With the exception of one
lipid (B-THF-14), the lipids were well tolerated, and no other animal was lost
due to systemic toxicity. The lipid which led to death was not found to be much
more toxic in cell culture than the other boron lipids. All of the lipids that
were well tolerated showed hemorrhage in both tumor models within a few hours
after administration. The hemorrhage could be seen by in vivo magnetic resonance
and histology, and was found to occur within a few hours. The degree of
hemorrhage depended on the amount of boron administered and on the tumor model.
The observed unwanted effect of the lipids precludes their use in boron neutron
capture therapy.
PMID- 25114528
TI - Enhanced activity of carbosilane dendrimers against HIV when combined with
reverse transcriptase inhibitor drugs: searching for more potent microbicides.
AB - Self-administered topical microbicides or oral preexposure prophylaxis could be
very helpful tools for all risk groups to decrease the human immunodeficiency
virus (HIV)-1 infection rates. Up until now, antiretrovirals (ARVs) have been the
most advanced microbicide candidates. Nevertheless, the majority of clinical
trials has failed in HIV-1 patients. Nanotechnology offers suitable approaches to
develop novel antiviral agents. Thereby, new nanosystems, such as carbosilane
dendrimers, have been shown to be safe and effective compounds against HIV with
great potential as topical microbicides. In addition, because most of the
attempts to develop effective topical microbicides were unsuccessful,
combinatorial strategies could be a valid approach when designing new
microbicides. We evaluated various combinations of anionic carbosilane dendrimers
with sulfated (G3-S16) and naphthyl sulfonated (G2-NF16) ended groups with
different ARVs against HIV-1 infection. The G3-S16 and G2-NF16 dendrimers showed
a synergistic or additive activity profile with zidovudine, efavirenz, and
tenofovir in the majority of the combinations tested against the X4 and R5 tropic
HIV-1 in cell lines, as well as in human primary cells. Therefore, the
combination of ARVs and polyanionic carbosilane dendrimers enhances the antiviral
potency of the individual compounds, and our findings support further clinical
research on combinational approaches as potential microbicides to block the
sexual transmission of HIV-1.
PMID- 25114531
TI - Perspectives on perceived stigma and self-stigma in adult male patients with
depression.
AB - There are two principal types of stigma in mental illness, ie, "public stigma"
and "self-stigma". Public stigma is the perception held by others that the
mentally ill individual is socially undesirable. Stigmatized persons may
internalize perceived prejudices and develop negative feelings about themselves.
The result of this process is "self-stigma". Stigma has emerged as an important
barrier to the treatment of depression and other mental illnesses. Gender and
race are related to stigma. Among depressed patients, males and African-Americans
have higher levels of self-stigma than females and Caucasians. Perceived stigma
and self-stigma affect willingness to seek help in both genders and races.
African-Americans demonstrate a less positive attitude towards mental health
treatments than Caucasians. Religious beliefs play a role in their coping with
mental illness. Certain prejudicial beliefs about mental illness are shared
globally. Structural modeling indicates that conformity to dominant masculine
gender norms ("boys don't cry") leads to self-stigmatization in depressed men who
feel that they should be able to cope with their illness without professional
help. These findings suggest that targeting men's feelings about their depression
and other mental health problems could be a more successful approach to change
help-seeking attitudes than trying to change those attitudes directly. Further,
the inhibitory effect of traditional masculine gender norms on help-seeking can
be overcome if depressed men feel that a genuine connection leading to mutual
understanding has been established with a health care professional.
PMID- 25114529
TI - 2'-(2-bromohexadecanoyl)-paclitaxel conjugate nanoparticles for the treatment of
non-small cell lung cancer in an orthotopic xenograft mouse model.
AB - A nanoparticle (NP) formulation with 2'-(2-bromohexadecanoyl)-paclitaxel (Br-16
PX) conjugate was developed in these studies for the treatment of non-small cell
lung cancer (NSCLC). The lipophilic paclitaxel conjugate Br-C16-PX was
synthesized and incorporated into lipid NPs where the 16-carbon chain enhanced
drug entrapment in the drug delivery system and improved in vivo
pharmacokinetics. The electron-withdrawing bromine group was used to facilitate
the conversion of Br-C16-PX to paclitaxel at the tumor site. The developed system
was evaluated in luciferase-expressing A549 cells in vitro and in an orthotopic
NSCLC mouse model. The results demonstrated that the Br-C16-PX NPs had a higher
maximum tolerated dose (75 mg/kg) than Taxol (19 mg/kg) and provided
significantly longer median survival (88 days versus 70 days, P<0.05) in the
orthotopic NSCLC model. An improved pharmacokinetic profile was observed for the
Br-C16-PX NPs at 75 mg/kg compared to Taxol at 19 mg/kg. The area under the
concentration versus time curve (AUC)0-96 h of Br-C16-PX from the NPs was 91.7
fold and 49.6-fold greater than Taxol in plasma and tumor-bearing lungs,
respectively, which provided sustained drug exposure and higher antitumor
efficacy in the NP-treated group.
PMID- 25114532
TI - Caregiver burden and coping strategies in caregivers of patients with Alzheimer's
disease.
AB - BACKGROUND: Alzheimer's disease (AD) causes considerable distress in caregivers
who are continuously required to deal with requests from patients. Coping
strategies play a fundamental role in modulating the psychologic impact of the
disease, although their role is still debated. The present study aims to evaluate
the burden and anxiety experienced by caregivers, the effectiveness of adopted
coping strategies, and their relationships with burden and anxiety. METHODS:
Eighty-six caregivers received the Caregiver Burden Inventory (CBI) and the State
Trait Anxiety Inventory (STAI Y-1 and Y-2). The coping strategies were assessed
by means of the Coping Inventory for Stressful Situations (CISS), according to
the model proposed by Endler and Parker in 1990. RESULTS: The CBI scores (overall
and single sections) were extremely high and correlated with dementia severity.
Women, as well as older caregivers, showed higher scores. The trait anxiety (STAI
Y-2) correlated with the CBI overall score. The CISS showed that caregivers
mainly adopted task-focused strategies. Women mainly adopted emotion-focused
strategies and this style was related to a higher level of distress. CONCLUSION:
AD is associated with high distress among caregivers. The burden strongly
correlates with dementia severity and is higher in women and in elderly subjects.
Chronic anxiety affects caregivers who mainly rely on emotion-oriented coping
strategies. The findings suggest providing support to families of patients with
AD through tailored strategies aimed to reshape the dysfunctional coping styles.
PMID- 25114533
TI - The relationship between insight and subjective experience in schizophrenia.
AB - OBJECTIVES: To examine the relationship between level of insight and various
subjective experiences for patients with schizophrenia. MATERIALS AND METHODS:
Seventy-four patients with schizophrenia who were discharged from our hospital
were evaluated. The level of insight into their illness and various subjective
experiences were evaluated at discharge. We used the Scale to Assess Unawareness
of Mental Disorder (SUMD) for evaluation of insight. In addition, five different
rating scales were used to evaluate subjective experiences: Subjective Experience
of Deficits in Schizophrenia (SEDS), Subjective Well-being under Neuroleptic drug
treatment Short form (SWNS), Schizophrenia Quality of Life Scale (SQLS), Beck
Depression Inventory (BDI), and the Drug Attitude Inventory (DAI)-30. RESULTS:
The SWNS and the scores for awareness of mental disorder and awareness of the
social consequences of mental disorder on SUMD showed a weak positive
correlation. The DAI-30 showed a significant negative correlation with most
general items on SUMD and a negative correlation between the subscale scores for
the awareness and attribution of past symptoms. SEDS, SWNS, SQLS, and the BDI
significantly correlated with the subscale scores for awareness of current
symptoms on SUMD, and weakly correlated with the subscale scores for attribution
of current negative symptoms. CONCLUSION: Awareness of subjective distress was
related to awareness of having a mental disorder. Feeling subjective distress was
related to awareness of current symptoms, as well as to the ability to attribute
current negative symptoms to a mental disorder. Positive attitudes toward
medication correlated with better general insight into the illness.
PMID- 25114534
TI - Sleep quality changes in insomniacs and non-insomniacs after acute altitude
exposure and its relationship with acute mountain sickness.
AB - OBJECTIVE: We aimed to observe the changes in subjective sleep quality among
insomniacs and non-insomniacs after acute ascending to 3,700 m and its possible
relationship with acute mountain sickness (AMS). METHODS: A total of 600 adult
men were recruited. Subjects' subjective sleep quality was evaluated by the
Athens Insomnia Scale. AMS was assessed using the Lake Louise scoring system.
Arterial oxygen saturation was measured. RESULTS: Despite insomnia resolution in
only a few subjects, the prevalence of insomnia among insomniacs remained stable
at 90% after rapid ascent to 3,700 m. However, among non-insomniacs, the
prevalence of insomnia sharply increased to 32.13% in the first day of altitude
exposure and progressively reduced to 4.26% by the 60th day of altitude stay.
Moreover, the prevalences of insomnia symptoms decreased more markedly from day 1
to day 60 at 3,700 m among non-insomniacs than among insomniacs. At 3,700 m, the
prevalence of AMS among insomniacs was 79.01%, 60.49%, and 32.10% on the first,
third, and seventh days, respectively, which was significantly higher than that
among non-insomniacs. Multivariate regression revealed that elevated Athens
Insomnia Scale scores are an independent risk factor for AMS (adjusted odds ratio
1.388, 95% confidence interval: 1.314-1.464, P<0.001), whereas high arterial
oxygen saturation and long duration of altitude exposure are protective factors
against AMS. CONCLUSION: Our results suggest that the effect of high-altitude
exposure on subjective sleep quality is more marked, but disappears more quickly,
among non-insomniacs than among insomniacs, whereas AMS is especially common
among insomniacs. Moreover, poor subjective sleep quality is a risk factor for
AMS.
PMID- 25114535
TI - Determinants of decision-to-intervention time in the management and therapeutic
outcome of emergency gynecological surgeries in south east Nigeria.
AB - BACKGROUND: Prompt and timely response in the management of gynecological
surgical cases can significantly affect the therapeutic surgical outcome of
patients in emergency situations. The aim of this study was to evaluate the
decision-to-intervention time (DIT), its determinants, and the significance in
the therapeutic outcome of emergency gynecological surgeries managed at a federal
teaching hospital in south east Nigeria over an 18-month period. METHODS: This
was a prospective descriptive study of 105 emergency gynecological cases managed
at a federal teaching hospital over an 18-month period. Patients were recruited
at the point of admission and followed up until discharge for outcome. Data were
abstracted with a data entry pro forma and then analyzed with the Epi InfoTM
statistical software version 7.0. RESULTS: The incidence of gynecological
surgical emergencies was 5.1% of the total gynecological cases managed during the
study period. The mean DIT was 4.25 (range 1.45-5.50) hours with delay in
intervention, mainly due to delays in securing blood/blood products and other
materials for resuscitation (46.7%) and a lack of finance (15.2%). Six maternal
deaths were recorded, giving a case fatality ratio of 5.7%, while the commonest
maternal complications associated with the delays were hemorrhage (61.9%) and the
need for blood transfusion (57.1%), respectively. The risk ratio of losing
>=1,000 mL of blood, anemia, hemorrhagic shock, and wound infection in those with
DIT >=120 minutes was statistically greater and significant at 95% confidence
interval. CONCLUSION: Inadequacies in health care services and policies due to
poor infrastructure, organizational framework, and financing were the major
determinants of the prolonged DIT and therapeutic outcomes.
PMID- 25114537
TI - New drugs to treat multidrug-resistant tuberculosis: the case for bedaquiline.
AB - Mycobacterium tuberculosis develops spontaneous resistance mutants to virtually
every drug in use. Courses of therapy select for these mutants and drug-resistant
organisms emerge. The development of drug-resistant organisms has reached the
point that drug resistance now threatens to undermine global success against
tuberculosis (TB). New drugs are needed. The last new class of drugs specifically
developed for treatment of TB was the rifamycins over 40 years ago. New funding
sources and the development of product development partnerships have energized
the TB drug development effort. There are now more TB drugs in development than
at any time in the past. The first of these drugs to be developed and marketed
was bedaquiline. Bedaquiline has an entirely novel mechanism of action and so
should be active against otherwise highly resistant organisms. It acts on the
transmembrane component of adenosine triphosphate synthase and acts by preventing
electron transport. This raises the exciting possibility that bedaquiline may be
active against less metabolically active organisms. Drug-drug interactions
between rifamycins and the cytochrome P450-3A system will limit bedaquiline's
utility and create complexity in treatment regimens. In clinical trials,
treatment with bedaquiline added to a background multidrug-resistant TB regimen
was associated with earlier culture conversion and higher cure rates, but there
were unexplained excess deaths in the bedaquiline arms of these trials. Food and
Drug Administration approved bedaquiline for the treatment of multidrug-resistant
TB when an effective treatment regimen cannot otherwise be provided. They
required a black box warning about excess deaths and require that a phase III
trial be completed. A planned Phase III trial is being reorganized. While
bedaquiline is an exciting drug and marks a dramatic moment in the history of TB
treatment, its ultimate place in the anti-TB drug armamentarium is unclear
pending the Phase III trial and the development of other new drugs that are in
the pipeline.
PMID- 25114538
TI - Process of implementing collaborative care and its impacts on the provision of
care and rehabilitation services to patients with a moderate or severe traumatic
brain injury.
AB - OBJECTIVE: The introduction of new services in a rehabilitation center is a
unique opportunity to introduce a new model of care and services between two
institutions. A hospital and a rehabilitation center experienced a clinical
management model inspired by an American approach - collaborative care. The
purpose of this study was to describe the implementation of this approach and to
provide a perception of the quality of care and services provided to patients
with moderate or severe traumatic brain injury and to their caregivers. MATERIALS
AND METHODS: In this qualitative study, individual semistructured interviews were
conducted with patients and their caregivers in the hospital and rehabilitation
center where the patients were treated. Individual semistructured interviews were
conducted with administrators, and two focus groups were held with clinicians
before and after the implementation. RESULTS AND CONCLUSION: Ten days' waiting
time were saved with the collaborative approach. Implementing the collaborative
care approach has been found to have several benefits, including improved
communication, coordination of services between institutions, and better
preparation, awareness, and involvement of patients and their families.
Administrators, clinicians, patients, and caregivers expressed their opinions on
the organization of care and services, the needs and expectations of patients and
their caregivers, their participation in terms of roles and responsibilities,
their perception of continuity of care, their satisfaction with the care process,
and their suggestions for improvements.
PMID- 25114536
TI - Optimal management of renal artery fibromuscular dysplasia.
AB - Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory angiopathy
of unknown cause affecting medium-sized (most commonly renal) arteries and
causing renovascular hypertension. The most common medial multifocal type of FMD
(with the "string of beads" appearance) is more than four times more prevalent in
females than in males. FMD accounts for up to 10% of cases of renovascular
hypertension. Compared with patients with atherosclerotic renal artery stenosis,
patients with FMD are younger, have fewer risk factors for atherosclerosis, and a
lower occurrence of atherosclerosis in other vessels. The etiology is
multifactorial, including vessel wall ischemia and smoking, as well as hormonal
and genetic factors. Intra-arterial digital subtraction angiography is still the
gold standard for exclusion or confirmation of renal artery stenosis caused by
FMD, at least in young patients, who more often have lesions in branches of the
renal artery. For FMD patients with atherosclerosis and those who are older (>50
55 years), significant renal artery stenosis may be confirmed or excluded with
ultrasonography. The FMD lesion is typically truncal or distal, whereas
atherosclerotic lesions are more often proximal or ostial. Treatment options are
medical, endovascular (percutaneous transluminal renal angioplasty [PTRA]), and
surgical. Invasive treatment should be considered when hypertension cannot be
controlled with antihypertensive drugs and in patients with impaired renal
function or ischemic nephropathy. PTRA has become the treatment of choice and
normally yields good results, especially in unifocal disease and young patients.
Pressure gradients are normally completely abolished, and there is no indication
for stent placement. Surgical revascularization is indicated after PTRA
complications; thrombosis, perforation, progressive dissection, repeated PTRA
failure or restenosis. Centralization of handling is recommended.
PMID- 25114541
TI - Mathematical Modeling and Data Analysis of NMR Experiments using Hyperpolarized
(13)C Metabolites.
AB - Rapid-dissolution dynamic nuclear polarization (DNP) has made significant impact
in the characterization and understanding of metabolism that occurs on the sub
minute timescale in several diseases. While significant efforts have been made in
developing applications, and in designing rapid-imaging radiofrequency (RF) and
magnetic field gradient pulse sequences, very few groups have worked on
implementing realistic mathematical/kinetic/relaxation models to fit the emergent
data. The critical aspects to consider when modeling DNP experiments depend on
both nuclear magnetic resonance (NMR) and (bio)chemical kinetics. The former
constraints are due to the relaxation of the NMR signal and the application of
'read' RF pulses, while the kinetic constraints include the total amount of each
molecular species present. We describe the model-design strategy we have used to
fit and interpret our DNP results. To our knowledge, this is the first report on
a systematic analysis of DNP data.
PMID- 25114540
TI - Safety and efficacy of gadobutrol-enhanced MRI in patients aged under 2 years-a
single-center, observational study.
AB - Gadobutrol is a 1-molar gadolinium-based contrast agent with well-characterized
safety and efficacy for magnetic resonance imaging (MRI) in adults and children
>= 2 years old. This observational study assessed gadobutrol-enhanced MRI in
children < 2 years of age. Sixty infants (mean age 11.1 months) underwent MRI
using gadobutrol at standard dose of 0.1 mL/kg (0.1 mmol/kg) body weight. MRI
examinations included brain, spine, and neck (n = 24), subcutaneous soft tissues
(n = 14), chest, abdomen, and pelvis (n = 12), musculoskeletal system (n = 7) and
vascular system (n = 3). No patients experienced adverse events related to
gadobutrol injection. In 57 patients with confirmed diagnoses, gadobutrol
enhanced MRI provided findings consistent with confirmed pathologies. This study
indicates that gadobutrol at a standard dose for MRI is safe in patients aged < 2
years and provides diagnostic information for multiple pathologies.
PMID- 25114539
TI - Design, implementation, and evaluation of a pediatric and adolescent type 2
diabetes management program at a tertiary pediatric center.
AB - Global rates of type 2 diabetes in children and adolescents have increased
significantly over the past three decades. Type 2 diabetes is a relatively new
disease in this age group, and there is a dearth of information about how to
structure treatment programs to manage its comorbidities and complications. In
this paper, we describe the design and implementation of a personalized
multidisciplinary, family-centered, pediatric and adolescent type 2 diabetes
program at a tertiary pediatric center in Hamilton, Ontario, Canada. We report
the process of designing and implementing such a program, and show that this
multidisciplinary program led to improvement in glycated hemoglobin (n=17, 8% at
baseline versus 6.4% at 1 year, 95% confidence interval (0.1-0.28), P-value
<0.0001) and stabilized body mass index, with lowered C-peptide and no change in
fitness or metabolic biomarkers of lipid metabolism and liver function. As type 2
diabetes becomes more prevalent in youth, the need for programs that successfully
address the complex nature of this disease is central to its management and to
mitigate its long-term adverse outcomes.
PMID- 25114542
TI - Effect of object orientation angle on t2* image and reconstructed magnetic
susceptibility: numerical simulations.
AB - The magnetic field resulting from material magnetization in magnetic resonance
imaging (MRI) has an object orientation effect, which produces an orientation
dependence for acquired T2* images. On one hand, the orientation effect can be
exploited for object anisotropy investigation (via multi-angle imaging); on the
other hand, it is desirable to remove the orientation dependence using magnetic
susceptibility reconstruction. In this report, we design a stick-star digital
phantom to simulate multiple orientations of a stick-like object and use it to
conduct various numerical simulations. Our simulations show that the object
orientation effect is not propagated to the reconstructed magnetic susceptibility
distribution. This suggests that accurate susceptibility reconstruction methods
should be largely orientation independent.
PMID- 25114544
TI - MR Spectroscopic Imaging of Peripheral Zone in Prostate Cancer Using a 3T MRI
Scanner: Endorectal versus External Phased Array Coils.
AB - Magnetic resonance spectroscopic imaging (MRSI) detects alterations in major
prostate metabolites, such as citrate (Cit), creatine (Cr), and choline (Ch). We
evaluated the sensitivity and accuracy of three-dimensional MRSI of prostate
using an endorectal compared to an external phased array "receive" coil on a 3T
MRI scanner. Eighteen patients with prostate cancer (PCa) who underwent
endorectal MR imaging and proton (1H) MRSI were included in this study.
Immediately after the endorectal MRSI scan, the PCa patients were scanned with
the external phased array coil. The endorectal coil-detected metabolite ratio
[(Ch+Cr)/Cit] was significantly higher in cancer locations (1.667 +/- 0.663)
compared to non-cancer locations (0.978 +/- 0.420) (P < 0.001). Similarly, for
the external phased array, the ratio was significantly higher in cancer locations
(1.070 +/- 0.525) compared to non-cancer locations (0.521 +/- 0.310) (P < 0.001).
The sensitivity and accuracy of cancer detection were 81% and 78% using the
endorectal 'receive' coil, and 69% and 75%, respectively using the external
phased array 'receive' coil.
PMID- 25114545
TI - Understanding the morphological mismatch between magnetic susceptibility source
and t2* image.
AB - BACKGROUND AND PURPOSE: Recent research has shown that a T2* image (either
magnitude or phase) is not identical to the internal spatial distribution of a
magnetic susceptibility (chi) source. In this paper, we examine the reasons
behind these differences by looking into the insights of T2*-weighted magnetic
resonance imaging (T2*MRI) and provide numerical characterizations of the
source/image mismatches by numerical simulations. METHODS: For numerical
simulations of T2*MRI, we predefine a 3D chi source and calculate the complex
valued T2* image by intravoxel dephasing in presence and absence of diffusion. We
propose an empirical alpha-power model to describe the overall source/image
transformation. For a Gaussian-shaped chi source, we numerically characterize the
source/image morphological mismatch in terms of spatial correlation and FWHM
(full width at half maximum). RESULTS: In theory, we show that the chi-induced
fieldmap is morphologically different from the chi source due to dipole effect,
and the T2* magnitude image is related to the fieldmap by a quadratic
transformation in the small phase angle regime, which imposes an additional
morphological change. The numerical simulations with a Gaussian-shaped chi source
show that a T2* magnitude image may suffer an overall source/image morphological
shrinkage of 20% to 25% and that the T2* phase image is almost identical to the
fieldmap thus maintaining a morphological mismatch from the chi source due to
dipole effect. CONCLUSION: The morphological mismatch between a bulk chi source
and its T2* image is caused by the 3D convolution during tissue magnetization
(dipole effect), the nonlinearity of the T2* magnitude and phase calculation, and
the spin diffusion effect. In the small phase angle regime, the T2* magnitude
exhibits an overall morphological shrinkage, and the T2* phase image suffers a
dipole effect but maintains the chi-induced fieldmap morphology.
PMID- 25114546
TI - Magnetic Resonance Imaging-derived Flow Parameters for the Analysis of
Cardiovascular Diseases and Drug Development.
AB - Nuclear magnetic resonance (NMR) allows for fast, accurate and noninvasive
measurement of fluid flow in restricted and non-restricted media. The results of
such measurements may be possible for a very small B 0 field and can be enhanced
through detailed examination of generating functions that may arise from
polynomial solutions of NMR flow equations in terms of Legendre polynomials and
Boubaker polynomials. The generating functions of these polynomials can present
an array of interesting possibilities that may be useful for understanding the
basic physics of extracting relevant NMR flow information from which various
hemodynamic problems can be carefully studied. Specifically, these results may be
used to develop effective drugs for cardiovascular-related diseases.
PMID- 25114543
TI - Magnetic resonance in the detection of breast cancers of different histological
types.
AB - Breast cancer incidence is increasing worldwide. Early detection is critical for
long-term patient survival, as is monitoring responses to chemotherapy for
management of the disease. Magnetic resonance imaging and spectroscopy (MRI/MRS)
has gained in importance in the last decade for the diagnosis and monitoring of
breast cancer therapy. The sensitivity of MRI/MRS for anatomical delineation is
very high and the consensus is that MRI is more sensitive in detection than x-ray
mammography. Advantages of MRS include delivery of biochemical information about
tumor metabolism, which can potentially assist in the staging of cancers and
monitoring responses to treatment. The roles of MRS and MRI in screening and
monitoring responses to treatment of breast cancer are reviewed here. We
rationalize how it is that different histological types of breast cancer are
differentially detected and characterized by MR methods.
PMID- 25114548
TI - Measuring restriction sizes using diffusion weighted magnetic resonance imaging:
a review.
AB - This article reviews a new concept in magnetic resonance as applied to cellular
and biological systems. Diffusion weighted magnetic resonance imaging can be used
to infer information about restriction sizes of samples being measured. The
measurements rely on the apparent diffusion coefficient changing with diffusion
times as measurements move from restricted to free diffusion regimes. Pulsed
gradient spin echo (PGSE) measurements are limited in the ability to shorten
diffusion times and thus are limited in restriction sizes which can be probed.
Oscillating gradient spin echo (OGSE) measurements could provide shorter
diffusion times so smaller restriction sizes could be probed.
PMID- 25114547
TI - Contrast-enhanced magnetic resonance imaging in pediatric patients: review and
recommendations for current practice.
AB - Magnetic resonance imaging (MRI), frequently with contrast enhancement, is the
preferred imaging modality for many indications in children. Practice varies
widely between centers, reflecting the rapid pace of change and the need for
further research. Guide-line changes, for example on contrast-medium choice,
require continued practice reappraisal. This article reviews recent developments
in pediatric contrast-enhanced MRI and offers recommendations on current best
practice. Nine leading pediatric radiologists from internationally recognized
radiology centers convened at a consensus meeting in Bordeaux, France, to discuss
applications of contrast-enhanced MRI across a range of indications in children.
Review of the literature indicated that few published data provide guidance on
best practice in pediatric MRI. Discussion among the experts concluded that MRI
is preferred over ionizing-radiation modalities for many indications, with
advantages in safety and efficacy. Awareness of age-specific adaptations in MRI
technique can optimize image quality. Gadolinium-based contrast media are
recommended for enhancing imaging quality. The choice of most appropriate
contrast medium should be based on criteria of safety, tolerability, and
efficacy, characterized in age-specific clinical trials and personal experience.
PMID- 25114552
TI - Chemo-enzymatic synthesis of glycolyl-ester-linked taxol-monosaccharide conjugate
and its drug delivery system using hepatitis B virus envelope L bio-nanocapsules.
AB - Chemo-enzymatic synthesis of glycolyl-ester-linked taxol-glucose conjugate, ie, 7
glycolyltaxol 2"-O-alpha-D-glucoside, was achieved by using alpha-glucosidase as
a biocatalyst. The water-solubility of 7-glycolyltaxol 2"-O-alpha-D-glucoside (21
MUM) was 53 fold higher than that of taxol. The hepatitis B virus envelope L
particles (bio-nanocapsules) are effective for delivering 7-glycolyltaxol 2"-O
alpha-D-glucoside to human hepatocellular carcinoma NuE cells.
PMID- 25114549
TI - MRS-based Metabolomics in Cancer Research.
AB - Metabolomics is a relatively new technique that is gaining importance very
rapidly. MRS-based metabolomics, in particular, is becoming a useful tool in the
study of body fluids, tissue biopsies and whole organisms. Advances in analytical
techniques and data analysis methods have opened a new opportunity for such
technology to contribute in the field of diagnostics. In the MRS approach to the
diagnosis of disease, it is important that the analysis utilizes all the
essential information in the spectra, is robust, and is non-subjective. Although
some of the data analytic methods widely used in chemical and biological sciences
are sketched, a more extensive discussion is given of a 5-stage Statistical
Classification Strategy. This proposes powerful feature selection methods, based
on, for example, genetic algorithms and novel projection techniques. The
applications of MRS-based metabolomics in breast cancer, prostate cancer,
colorectal cancer, pancreatic cancer, hepatobiliary cancers, gastric cancer, and
brain cancer have been reviewed. While the majority of these applications relate
to body fluids and tissue biopsies, some in vivo applications have also been
included. It should be emphasized that the number of subjects studied must be
sufficiently large to ensure a robust diagnostic classification. Before MRS-based
metabolomics can become a widely used clinical tool, however, certain challenges
need to be overcome. These include manufacturing user-friendly commercial
instruments with all the essential features, and educating physicians and medical
technologists in the acquisition, analysis, and interpretation of metabolomics
data.
PMID- 25114550
TI - In vivo monitoring of natural killer cell trafficking during tumor immunotherapy.
AB - Natural killer (NK) cells are a crucial part of the innate immune system and play
critical roles in host anti-viral, anti-microbial, and antitumor responses. The
elucidation of NK cell biology and their therapeutic use are actively being
pursued with 200 clinical trials currently underway. In this review, we outline
the role of NK cells in cancer immunotherapies and summarize current noninvasive
imaging technologies used to track NK cells in vivo to investigate mechanisms of
action, develop new therapies, and evaluate efficacy of adoptive transfer.
PMID- 25114554
TI - Plant-based Paste Fermented by Lactic Acid Bacteria and Yeast: Functional
Analysis and Possibility of Application to Functional Foods.
AB - A plant-based paste fermented by lactic acid bacteria and yeast (fermented paste)
was made from various plant materials. The paste was made of fermented food by
applying traditional food-preservation techniques, that is, fermentation and
sugaring. The fermented paste contained major nutrients (carbohydrates, proteins,
and lipids), 18 kinds of amino acids, and vitamins (vitamin A, B1, B2, B6, B12,
E, K, niacin, biotin, pantothenic acid, and folic acid). It contained five kinds
of organic acids, and a large amount of dietary fiber and plant phytochemicals.
Sucrose from brown sugar, used as a material, was completely resolved into
glucose and fructose. Some physiological functions of the fermented paste were
examined in vitro. It was demonstrated that the paste possessed antioxidant,
antihypertensive, antibacterial, anti-inflammatory, anti-allergy and anti
tyrosinase activities in vitro. It was thought that the fermented paste would be
a helpful functional food with various nutrients to help prevent lifestyle
diseases.
PMID- 25114551
TI - Dying for Good: Virus-Bacterium Biofilm Co-evolution Enhances Environmental
Fitness.
AB - Commonly used in biotechnology applications, filamentous M13 phage are non-lytic
viruses that infect E. coli and other bacteria, with the potential to promote
horizontal gene transfer in natural populations with synthetic biology
implications for engineering community systems. Using the E. coli strain TG1, we
have investigated how a selective pressure involving elevated levels of toxic
chromate, mimicking that found in some superfund sites, alters population
dynamics following infection with either wild-type M13 phage or an M13-phage
encoding a chromate reductase (Gh-ChrR) capable of the reductive immobilization
of chromate (ie, M13-phageGh-ChrR). In the absence of a selective pressure, M13
phage infection results in a reduction in bacterial growth rate; in comparison,
in the presence of chromate there are substantial increases in both cellular
killing and biomass formation following infection of E. coli strain TG1with M13
phageGh-ChrR that is dependent on chromate-reductase activity. These results are
discussed in terms of community structures that facilitate lateral gene transfer
of beneficial traits that enhance phage replication, infectivity, and stability
against environmental change.
PMID- 25114553
TI - Chemo-enzymatic synthesis of ester-linked 2-phenylindole-3-carboxaldehyde
monosaccharide conjugate as potential prodrug.
AB - Chemo-enzymatic synthesis of ester-linked 2-phenylindole-3-carboxaldehyde-glucose
conjugate (2-phenylindole-3-carboxyl-10"-O-beta-D-glucosyl ester) was achieved by
using plant cell cultures as biocatalysts. The anticancer agent, 2-phenylindole-3
carboxaldehyde, induced apoptosis in cells, whereas 2-phenylindole-3-carboxyl-10"
O-beta-D-glucosyl ester showed no cytotoxicity and induced no apoptosis.
PMID- 25114555
TI - The impact of a diabetes self-management education program provided through a
telemedicine link to rural california health care clinics.
AB - BACKGROUND: This project investigated the impact of a DM self-management
education program provided through a telemedicine link at nine rural health
clinics in Northern California. METHODS: Two hundred thirty nine patients were
provided with a single 2-hour class on DM delivered through a live televideo
connection. Patients provided pre-intervention information on: demographics and
overall health, self-care behaviors, and knowledge about DM. All participants
completed a post-education survey on knowledge and self-care behaviors. RESULTS:
There was a significant decrease in the number of patients who felt overwhelmed
with their DM; pre-intervention 18.8%; post-intervention 5.4% (P < 0.0001).
Patients increased the number of days they exercised; pre-intervention 3.4 days;
post-intervention 3.9 days (P = 0.02). Patients increased the number of days they
checked their feet; pre-intervention 4.2 days; post-intervention 5.6 days (P <
0.01). Knowledge about DM improved over the study period (P < 0.01). CONCLUSIONS:
A single 2-hour class on DM administered through a telemedicine link to patients
in rural health clinics resulted in feeling less overwhelmed, more knowledgeable
about DM, and demonstrated an increase in self-care behavior; ie, exercise and
foot care.
PMID- 25114556
TI - Quality of health assistants in primary health centres in rural maharashtra,
India.
AB - INTRODUCTION: Health assistants are important functionaries of the primary health
care system in India. Their role is supervision of field-based services among
other things. A quality assurance mechanism for these health assistants is
lacking. The present study was undertaken with the objectives of developing a
tool to assess the quality of health assistants in primary health centres (PHCs)
and to assess their quality using this tool. METHODOLOGY: Health assistants from
three PHCs in the Wardha district of India were observed for a year using a tool
developed from primary health care management Aavancement program modules. Data
was collected by direct observation, interview, and review of records for quality
of activities. RESULTS: Staff strength of health assistants was 87.5%. None of
the health assistants were clear about their job descriptions. A supervisory
schedule for providing supportive supervision to auxiliary nurse midwives (ANMs)
was absent; most field activities pertaining to maternal and child health
received poor focus. Monthly meetings lacked a clear agenda, and comments on
quality improvement of services provided by the ANMs were missing. CONCLUSION:
Continuous training with sensitization on quality issues is required to improve
the unsatisfactory quality.
PMID- 25114558
TI - Management options for patients with chronic back pain without an etiology.
AB - The treatment and management of low back pain is complex when there is no
specific etiology such as cancer, fracture, or herniated disc. An organized
approach to management that follows evidence based guidelines will facilitate
care in a problem that reflects a lifetime prevalence of over 70 percent. The
purpose of this review is to present a guideline to care for a common disabling
process with a very heterogeneous etiology.
PMID- 25114559
TI - Narcotics in rheumatology.
AB - Patients with rheumatic conditions often suffer from related chronic pain. When
first-line traditional medications such as acetaminophen and anti-inflammatory
medications do not suffice, then other options are needed. The traditional
medications may ultimately not provide sufficient pain relief, or alternatively,
they can pose as a contraindication due to underlying hypertension, renal, and/or
hepatic disease. Therefore, narcotics are an alluring alternative, which if used
in a multidisciplinary and systematic approach to the patient, can prove to be
quite beneficial in the lives of these patients.
PMID- 25114557
TI - Behavioral lifestyle intervention in the treatment of obesity.
AB - This article provides an overview of research regarding adult behavioral
lifestyle intervention for obesity treatment. We first describe two trials using
a behavioral lifestyle intervention to induce weight loss in adults, the Diabetes
Prevention Program (DPP) and the Look AHEAD (Action for Health in Diabetes)
trial. We then review the three main components of a behavioral lifestyle
intervention program: behavior therapy, an energy- and fat-restricted diet, and a
moderate- to vigorous-intensity physical activity prescription. Research
regarding the influence of dietary prescriptions focusing on macronutrient
composition, meal replacements, and more novel dietary approaches (such as
reducing dietary variety and energy density) on weight loss is examined. Methods
to assist with meeting physical activity goals, such as shortening exercise
bouts, using a pedometer, and having access to exercise equipment within the
home, are reviewed. To assist with improving weight loss outcomes, broadening
activity goals to include resistance training and a reduction in sedentary
behavior are considered. To increase the accessibility of behavioral lifestyle
interventions to treat obesity in the broader population, translation of
efficacious interventions such as the DPP, must be undertaken. Translational
studies have successfully altered the DPP to reduce treatment intensity and/or
used alternative modalities to implement the DPP in primary care, worksite, and
church settings; several examples are provided. The use of new methodologies or
technologies that provide individualized treatment and real-time feedback, and
which may further enhance weight loss in behavioral lifestyle interventions, is
also discussed.
PMID- 25114561
TI - Patient-Reported Outcomes (PROs) and Patient-Reported Outcome Measures (PROMs).
AB - In recent years, there has been an increased focus on placing patients at the
center of health care research and evaluating clinical care in order to improve
their experience and ensure that research is both robust and of maximum value for
the use of medicinal products, therapy, or health services. This paper provides
an overview of patients' involvement in clinical research and service evaluation
along with its benefits and limitations. We describe and discuss patient-reported
outcomes (PROs) and patient-reported outcome measures (PROMs), including the
trends in current research. Both the patient-reported experiences measures
(PREMs) and patient and public involvement (PPI) initiative for including
patients in the research processes are also outlined. PROs provide reports from
patients about their own health, quality of life, or functional status associated
with the health care or treatment they have received. PROMs are tools and/or
instruments used to report PROs. Patient report experiences through the use of
PREMs, such as satisfaction scales, providing insight into the patients'
experience with their care or a health service. There is increasing international
attention regarding the use of PREMS as a quality indicator of patient care and
safety. This reflects the ongoing health service commitment of involving patients
and the public within the wider context of the development and evaluation of
health care service delivery and quality improvement.
PMID- 25114562
TI - Age-friendly primary health care: an assessment of current service provision for
older adults in Hong Kong.
AB - There has been no study evaluating whether primary care services are sufficiently
oriented towards the older population in Hong Kong, particularly those with
increasing frailty. Since primary care is a key first interface in promotion and
maintenance of health in older people, an assessment of the age-friendliness of
service provisions is of critical importance in optimizing the health of aging
populations. The age-friendliness of primary care services for older people was
assessed using focus groups of elderly people and also of service providers who
care for them. Discussion content was based on the WHO guidelines for age
friendly primary care in the following areas: Information, education and
training, community-based health care management systems, and the physical
environment. Desirable improvements were identified in all domains. The findings
underscore the need for wider dissemination of health care needs of older people
in the primary care setting.
PMID- 25114560
TI - Reducing the risk of harm from medication errors in children.
AB - MEDICATION ERRORS AFFECT THE PEDIATRIC AGE GROUP IN ALL SETTINGS: outpatient,
inpatient, emergency department, and at home. Children may be at special risk due
to size and physiologic variability, limited communication ability, and treatment
by nonpediatric health care providers. Those with chronic illnesses and on
multiple medications may be at higher risk of experiencing adverse drug events.
Some strategies that have been employed to reduce harm from pediatric medication
errors include e-prescribing and computerized provider order entry with decision
support, medication reconciliation, barcode systems, clinical pharmacists in
medical settings, medical staff training, package changes to reduce look
alike/sound-alike confusion, standardization of labeling and measurement devices
for home administration, and quality improvement interventions to promote
nonpunitive reporting of medication errors coupled with changes in systems and
cultures. Future research is needed to measure the effectiveness of these
preventive strategies.
PMID- 25114563
TI - Behavioral interventions associated with smoking cessation in the treatment of
tobacco use.
AB - Tobacco smoke is the leading cause of preventable premature death worldwide.
While the majority of smokers would like to stop, the habitual and addictive
nature of smoking makes cessation difficult. Clinical guidelines suggest that
smoking cessation interventions should include both behavioural support and
pharmacotherapy (e.g. nicotine replacement therapy). This commentary paper
focuses on the important role of behavioural interventions in encouraging and
supporting smoking cessation attempts. Recent developments in the field are
discussed, including 'cut-down to quit', the behaviour change techniques taxonomy
(BCTT) and very brief advice (VBA) on smoking. The paper concludes with a
discussion of the important role that health professionals can and should play in
the delivery of smoking cessation interventions.
PMID- 25114564
TI - Maintaining a Sufficient and Quality Physician Workforce: The Role of For-profit
Medical Schools.
AB - Currently, in the United States there is a significant physician workforce
shortage. This problem is likely to persist as there is no quick solution. The
nature of this shortage is complex and involves factors such as an absolute
physician shortage, as well as physician shortages in primary care and certain
specialty care areas. In addition, there is a misdistribution of physicians to
medically underserved areas and populations. The medical education system trains
medical school graduates that eventually feed the physician workforce. However,
several factors are in place which ultimately limits the effectiveness of this
system in providing an appropriate workforce to meet the population demands. For
profit medical schools have been in existence in and around the continental US
for many years and some authors have suggested that they may be a major
contributor to the physician workforce shortage. There is currently one for
profit medical school in the US, however the majority exist in the Caribbean. The
enrollment in and number of these schools have grown to partially meet the ever
growing demand for an increase in medical school graduates and they continue to
provide a large number of graduates who return to the US for postgraduate medical
training and, ultimately, increase the physician workforce. The question is
whether this source will benefit the workforce quality and quantity needs of our
growing and aging population.
PMID- 25114565
TI - Adolescent sleep and cellular phone use: recent trends and implications for
research.
AB - Adolescent sleep needs range from 8.5-10 hours per night, with older adolescents
requiring less sleep than younger adolescents. On average, however, American
adolescents receive between 7.5-8.5 hours of sleep per night, with many sleeping
fewer than 6.5 hours on school nights. Cellular phone use is emerging as an
important factor that interferes with both sleep quality and quantity,
particularly as smartphones become more widely available to teens. This review
paper has three objectives. First, we will describe adolescent sleep patterns and
the effects of sleep deprivation on adolescent physical and mental health.
Second, we will describe current trends in technology use among adolescents,
making associations to how technology impacts sleep. Lastly, we will discuss some
of the methodological barriers of conducting sleep and technology research with
adolescents and young adults and offer suggestions for overcoming those barriers.
We will also discuss implications for healthcare providers.
PMID- 25114566
TI - The function of a medical director in healthcare institutions: a master or a
servant.
AB - The function of a medical director is presented along with features of efficiency
and deficiencies from the perspective of healthcare system improvement. A
MEDLINE/Pubmed research was performed using the terms "medical director" and
"director", and 50 relevant articles were selected. Institutional healthcare
quality is closely related to the medical director efficiency and deficiency, and
a critical discussion of his or her function is presented along with a focus on
the institutional policies, protocols, and procedures. The relationship between
the medical director and the executive director is essential in order to
implement a successful healthcare program, particularly in private facilities.
Issues related to professionalism, fairness, medical records, quality of care,
patient satisfaction, medical teaching, and malpractice are discussed from the
perspective of institutional development and improvement strategies. In summary,
the medical director must be a servant to the institutional constitution and to
his or her job description; when his or her function is fully implemented, he or
she may represent a local health governor or master, ensuring supervision and
improvement of the institutional healthcare system.
PMID- 25114567
TI - Use of GIS Mapping as a Public Health Tool-From Cholera to Cancer.
AB - The field of medical geographic information systems (Medical GIS) has become
extremely useful in understanding the bigger picture of public health. The
discipline holds a substantial capacity to understand not only differences, but
also similarities in population health all over the world. The main goal of
marrying the disciplines of medical geography, public health and informatics is
to understand how countless health issues impact populations, and the trends by
which these populations are affected. From the 1990s to today, this practical
approach has become a valued and progressive system in analyzing medical and
epidemiological phenomena ranging from cholera to cancer. The instruments
supporting this field include geographic information systems (GIS), disease
surveillance, big data, and analytical approaches like the Geographical Analysis
Machine (GAM), Dynamic Continuous Area Space Time Analysis (DYCAST), cellular
automata, agent-based modeling, spatial statistics and self-organizing maps. The
positive effects on disease mapping have proven to be tremendous as these
instruments continue to have a great impact on the mission to improve worldwide
health care. While traditional uses of GIS in public health are static and
lacking real-time components, implementing a space-time animation in these
instruments will be monumental as technology and data continue to grow.
PMID- 25114569
TI - A Group Interview Regarding Disaster Preparedness for Food Assistance in a
University that Offers a Training Course for Registered Dietitians.
AB - Mass care feeding for disaster evacuees is an important component of public
health preparedness. If universities that offer a training course for registered
dietitians could provide food assistance to the evacuated people in their campus,
it could contribute to maintain their health. Many universities are expected to
become a base of support activities for people affected by disaster. This study
aimed to reveal disaster preparedness in a university that offers a training
course for registered dietitians, from the aspect of provision of mass care
feeding. As Japan has 124 universities that offer such training courses, this
case study could serve as a useful reference for them and contribute to the
improvement of health of the affected people. A group interview was conducted in
University A in 2012. The participants included two faculty members in the
course, a vice president, a staff member, and a faculty member in charge of
disaster preparedness and response. Stockpiled foods were limited to dry bread
and pre-processed rice. No alternative heat sources were stored. It was concluded
that to provide nutrients other than carbohydrate, hot meals should be served for
the evacuees. Additionally, it would be difficult to provide meal service when
the essential utilities such as gas and electricity are disrupted.
PMID- 25114568
TI - Quality of care and quality of life: convergence or divergence?
AB - The aim of this study was to explore the impact of quality of care (QoC) on
patients' quality of life (QoL). In a cross-sectional study, two domains of QoC
and the World Health Organization Quality of Life-Bref questionnaire were
combined to collect data from 1,059 pre-discharge patients in four accredited
hospitals (ACCHs) and four non-accredited hospitals (NACCHs) in Saudi Arabia.
Health and well-being are often restricted to the characterization of sensory
qualities in certain settings such as unrestricted access to healthcare,
effective treatment, and social welfare. The patients admitted to tertiary health
care facilities are generally able to present themselves with a holistic approach
as to how they experience the impact of health policy. The statistical results
indicated that patients reported a very limited correlation between QoC and QoL
in both settings. The model established a positive, but ultimately weak and
insignificant, association between QoC (access and effective treatment) and QoL
(r = 0.349, P = 0.000; r = 0.161, P = 0.000, respectively). Even though the two
settings are theoretically different in terms of being able to conceptualize,
adopt, and implement QoC, the outcomes from both settings demonstrated
insignificant relationships with QoL as the results were quite similar. Though
modern medicine has substantially improved QoL around the world, this paper
proposes that health accreditation has a very limited impact on improving QoL.
This paper raises awareness of this topic with multiple healthcare professionals
who are interested in correlating QoC and QoL. Hopefully, it will stimulate
further research from other professional groups that have new and different
perspectives. Addressing a transitional health care system that is in the process
of endorsing accreditation, investigating the experience of tertiary cases, and
analyzing deviated data may limit the generalization of this study. Global
interest in applying public health policy underlines the impact of such process
on patients' outcomes. As QoC accreditation does not automatically produce
improved QoL outcomes, the proposed study encourages further investigation of the
value of health accreditation on personal and social well-being.
PMID- 25114570
TI - Anonymity: an impediment to performance in healthcare.
AB - Many teaching hospitals employ a care team structure composed of a broad range of
healthcare providers with different skill sets. Each member of this team has a
distinct role and a different level of training ranging from attending physician
to resident, intern, and medical student. Often times, these different roles lead
to greater complexity and confusion for both patients and nursing staff. It has
been demonstrated that patients have a great degree of difficulty in identifying
members of their care team. This anonymity also exists between nursing staff and
other care providers. In order to better understand the magnitude of anonymity
within the teaching hospital, a ten-question survey was sent to nurses across
three different departments. Results from this survey demonstrated that 71% of
nurses are "Always" or "Often" able to identify which care team is responsible
for their patients, while 79% of nurses reported that they either "Often" or
"Sometimes" page a provider who is not currently caring for a given patient.
Furthermore, 33% of nurses felt that they were either "Rarely" or "Never" able to
recognize, by face and name, attending level providers. Residents were "Rarely"
or "Never" recognized by face and name 37% of the time, and interns 42% of the
time. Contacting the wrong provider repeatedly leads to de facto delays in
medication, therapy, and diagnosis. Additionally, these unnecessary interruptions
slow workflow for both nurses and members of the care team, making hospital care
less efficient and safe overall. Technological systems should focus on reducing
anonymity within the hospital in order to enhance healthcare delivery.
PMID- 25114571
TI - Ambulatory and Hospital-based Quality Improvement Methods in Israel.
AB - This review article compares ambulatory and hospital-based quality improvement
methods in Israel. Data were collected from: reports of the National Program for
Quality Indicators in community, the National Program for Quality Indicators in
Hospitals, and from the Organization for Economic Cooperation and Development
(OECD) Reviews of Health Care Quality.
PMID- 25114572
TI - Prognostic significance of thymidylate synthase in postoperative non-small cell
lung cancer patients.
AB - The aim of the present study was to investigate the clinicopathologic/prognostic
significance of thymidylate synthase (TS), orotate phosphoribosyltransferase
(OPRT), and thymidine phosphorylase (TP) proteins in postoperative non-small cell
lung cancer (NSCLC) patients. Microarray slides from a set of 178 NSCLC patients
were used for the detection of TS, OPRT, and TP expression by
immunohistochemistry. The correlation between clinicopathologic factors and
protein expression of three proteins was analyzed. Ninety seven carcinomas
(57.4%) were TS-positive, 90 carcinomas (53.9%) were OPRT-positive, and 102
carcinomas (69.4%) were TP-positive. Compared with the TS-positive patients, the
overall survival (OS) was significantly lower in the TS-negative patients (hazard
ratio [HR] =1.766, 95% confidence interval [CI] =1.212-2.573, P=0.003).
Significant differences between TS-positive and TS-negative patients was also
observed in the following stratified analyses: 1) adenocarcinoma subgroup (HR
=2.079, 95% CI =1.235-3.500, P=0.006); 2) less than 60-year-old subgroup (HR
=1.890, 95% CI =1.061-3.366, P=0.031); 3) stage II/III subgroup (HR =1.594, 95%
CI =1.036-2.453, P=0.034); and 4) surgery plus adjuvant therapy subgroup (HR
=1.976, 95% CI =1.226-3.185, P=0.005). However, the OS was not significantly
correlated with OPRT or TP protein expression. This study demonstrates that the
TS level in tumor tissues may be a useful marker to predict the postoperative OS
in NSCLC patients.
PMID- 25114574
TI - Paclitaxel- and/or cisplatin-induced ocular neurotoxicity: a case report and
literature review.
AB - Paclitaxel (PTX) and/or cisplatin (CDDP), as important cytotoxic anti-cancer
agents, are widely used to treat various solid tumors. Both may cause moderate or
severe neurotoxicity, but ocular neurotoxicity is also occasionally reported. A
patient diagnosed with nasopharyngeal cancer suffering acute ocular neurotoxicity
10 days after paclitaxel and CDDP administration at the recommended dose is
described in the present case report, and PTX- and/or CDDP-induced ocular
neurotoxicity are summarized according to previous reports. Possible mechanisms
and the potential diagnostic, therapeutic and predictive strategies of PTX-
and/or CDDP-induced ocular neurotoxicity are reviewed, to help the oncologist to
take the infrequent toxicity of cytotoxic drugs into account and improve patient
safety during anti-cancer therapy.
PMID- 25114573
TI - PD-1 as an emerging therapeutic target in renal cell carcinoma: current evidence.
AB - Renal cell carcinoma (RCC) is the most common primary malignant tumor of the
kidney in adults, representing approximately 4% of all adult cancers in the
United States. Metastatic RCC is poorly responsive to conventional cytotoxic
chemotherapies but can be sensitive to T-cell-directed immunotherapies such as
interferon-alpha or interleukin-2. Despite recent progress in the application of
antiangiogenic "targeted therapies" for metastatic RCC, high-dose interleukin-2
remains an appropriate first-line therapy for select patients and is associated
with durable complete remissions in a small fraction of treated patients. Thus,
advanced RCC provides a unique opportunity to investigate the requirements for
effective antitumor immunotherapy. Accumulating evidence suggests that resistance
mechanisms exploited by RCC and other tumor types may play a dominant role in
limiting the effectiveness of tumor-reactive adaptive immune responses.
Expression of the inhibitory coreceptor programmed cell death-1 (PD-1) on tumor
infiltrating lymphocytes within RCC tumors, as well as the expression of the PD-1
ligand (PD-L1) on RCC tumor cells, are strong negative prognostic markers for
disease-specific death in RCC patients. Monoclonal antibodies targeting either PD
1 or PD-L1 have now entered clinic trials and have demonstrated promising
antitumor effects for refractory metastatic RCC. This review summarizes the
results of published and reported studies of PD-1- and PD-L1-targeted therapies
enrolling patients with advanced RCC, focusing on key safety, toxicity, and
efficacy end points. Prospects for advanced phase clinical testing and novel
therapy combinations with PD-1- and PD-L1-targeted agents are discussed.
PMID- 25114576
TI - Prevalence of metabolic syndrome and its components based on a harmonious
definition among adults in Morocco.
AB - PURPOSE: Metabolic syndrome is a cluster of risk factors for diabetes and
cardiovascular diseases that includes central obesity, hypertension, glucose
intolerance, high triglyceride, and low high-density lipoprotein cholesterol. Its
prevalence is rapidly increasing worldwide. This study aimed to estimate the
prevalence of metabolic syndrome and associated risk factors in a representative
sample of Morocco adults using the 2009 joint interim statement definition.
PATIENTS AND METHODS: We analyzed data of 820 patients aged 19 years and older.
For metabolic syndrome diagnosis, we used the criteria of the recently published
joint interim statement (2009). RESULTS: The prevalence of metabolic syndrome is
35.73% among all adults, 18.56% among men, and 40.12% among women. Prevalence
increased with age, peaking among those aged 50-59 years. The most common
abnormality highlights abdominal obesity (49.15%). Also, half of patients have
one or two risk factors for developing this syndrome. CONCLUSION: The prevalence
of metabolic syndrome and associated risk factors is high among adults in
Morocco, especially in women. The most prevalent component of metabolic syndrome
in our population was abdominal obesity.
PMID- 25114575
TI - Lapatinib for the treatment of breast cancer in the People's Republic of China.
AB - Lapatinib is an oral, small-molecule, reversible inhibitor of both epidermal
growth factor receptor and human epidermal growth factor receptor-2 (HER2)
tyrosine kinases. In March 2007, the US Food and Drug Administration approved
lapatinib for use in combination with capecitabine for the treatment of women
with HER2-overexpressing, advanced or metastatic breast cancer. This review
discusses the available information of lapatinib in Chinese breast cancer
patients, focusing on its effectiveness and clinical application against advanced
or metastatic breast cancer. In pivotal phase III trials, a combination of
lapatinib and capecitabine significantly decreased the risk of disease
progression compared to capecitabine alone in women with HER2-positive advanced
or metastatic breast cancer. Other trials were used to evaluate lapatinib in
combination with hormone therapy, in combination with trastuzumab, and as an
adjunct to adjuvant therapy for early-stage disease. Preclinical data have
revealed that lapatinib is active in trastuzumab-resistant cell lines as well as
synergistic with trastuzumab. In clinical trials, lapatinib has not been
associated with serious or symptomatic cardiotoxicity. Further, it can cross the
blood-brain barrier and may therefore have a role in preventing cancer
progression in the central nervous system. Thus, lapatinib warrants further
evaluation in HER2-positive metastatic and early-stage breast cancer patients.
PMID- 25114577
TI - Elevated body mass index as a risk factor for chronic kidney disease: current
perspectives.
AB - Chronic kidney disease (CKD) is defined by the National Kidney Foundation Kidney
Disease Outcomes Quality Initiative as the presence of reduced kidney function or
kidney damage for a period of 3 months or greater. Obesity is considered a risk
factor for CKD development, but its precise role in contributing to CKD and end
stage kidney disease is not fully elucidated. In this narrative review, the
objectives are to describe the pathogenesis of CKD in obesity, including the
impact of altered adipokine secretion in obesity and CKD, and to provide an
overview of the clinical studies assessing the risk of obesity and CKD
development.
PMID- 25114579
TI - Partners of patients with inflammatory bowel disease: how important is their
support?
AB - BACKGROUND: Chronic inflammatory bowel disease (IBD) causes significant distress
for patients and their families. Data assessing the need of these patients for
support and sharing with their partners are scarce. The aim of this study was to
assess patients' views regarding sharing of information with their partners.
METHODS: Ambulatory IBD patients treated at the Chaim Sheba Medical Center
between January 2011 and January 2013 were asked to complete an anonymous
questionnaire. Patients who had a stable partner and completed more than 95% of
the questionnaire were included. RESULTS: Of 134 patients who agreed to complete
the questionnaire, 101 met the inclusion criteria, 53 were men (mean age 45+/-15
years), and 50% had academic education. Only 42% of patients reported that their
partner accompanied them to the doctor. However, 93% shared health problems with
their partner, 64% would have liked their partner to receive more medical
information, and 70% would like their partner to be more involved. The majority
(88%) believed that more partner involvement could help them deal better with the
disease, and 70% thought that support groups for partners should be established.
No association was found between patients' demographic data and their answers.
Patients who felt that partner involvement could help them to deal with the
disease tended to share medical information with their partners and wanted them
to be more involved in health care decision-making (P<0.001). CONCLUSION: Most
IBD patients in our study wanted their partner to be more involved with their
health problems, and believed that greater partner involvement could help them
deal better with their disease. Therefore, more attention should be focused on
gaining better cooperation from patients' families.
PMID- 25114578
TI - Is adherence a relevant issue in the self-management education of diabetes? A
mixed narrative review.
AB - While therapeutic patient education is now recognized as essential for optimizing
the control of chronic diseases and patient well-being, adherence to treatment
and medical recommendations is still a matter of debate. In type 2 diabetes, the
nonadherence to therapy, estimated at more than 40%, is perceived as a barrier
for improving the prognosis despite recent therapeutic advances. Interventional
studies have barely begun to demonstrate the effectiveness of technical and
behavioral actions. The aim of this review is to question the concept of
adherence in terms of therapeutic education based on quantitative and qualitative
data. The research on therapeutic education has shown the effectiveness of
structured actions in type 2 diabetes, but adherence is rarely an end point in
randomized trials. A positive but inconsistent or moderate effect of education
actions on adherence has been shown in heterogeneous studies of varying quality.
Program types, outlines, theoretical bases, and curricula to set up for action
effectiveness are still being discussed. Qualitative studies, including
sociological studies, provide a useful and constructive focus on this
perspective. Adherence is a soft and flexible tool available to the patient in
his/her singular chronic disease trajectory, and as such, integrates into
individual therapeutic strategies, including socio-cultural interactions, beyond
the medical explanation of the disease and the patient. Four key elements for the
development of structured therapeutic education are discussed: 1) the access to
health literacy, 2) the contextualization of education activities, 3) the long
term chronic dimension of self-management, and 4) the organizational aspects of
health and care. Rather than focusing the objective on behavioral changes,
structured therapeutic education actions should attempt to provide tools and
resources aimed at helping individuals to manage their disease in their own
context on a long-term basis, by developing health literacy and relational and
organizational aspects of the health professionals and system.
PMID- 25114580
TI - Improving the prognosis of nephropathic cystinosis.
AB - Cystinosis is an autosomal recessive inherited lysosomal storage disease. It is
characterized by generalized proximal tubular dysfunction known as renal Fanconi
syndrome and causes end-stage renal disease by the age of about 10 years if left
untreated. Extrarenal organs are also affected, including the thyroid gland,
gonads, pancreas, liver, muscle, and brain. Treatment consists of administration
of cysteamine, resulting in depletion of cystine that is trapped inside the
lysosomes. Since cysteamine has a short half-life, it should be administered
every 6 hours. Recently, a new delayed-release formulation was marketed, that
should be administered every 12 hours. The first studies comparing both
cysteamine formulations show comparable results regarding white blood cell
cystine depletion (which serves as a measure for cystine accumulation in the
body), while a slightly lower daily dose of cysteamine can be used.
PMID- 25114581
TI - CYP19A1 single nucleotide polymorphism associations with CYP19A1, NFkappaB1, and
IL6 gene expression in human normal colon and normal liver samples.
AB - BACKGROUND: Estrogen is known to decrease the risk of colon cancer in
postmenopausal women, and may exert its actions by decreasing interleukin-6 (IL6)
production via stabilization of the transcription factor nuclear factor kappa
light-chain-enhancer of activated B cells (NFkappaB). Estrogens are
biosynthesized by CYP19A1 (aromatase), so it is possible that genetic variations
in CYP19A1 influences the risk of colon cancer by altering expression of CYP19A1.
Further, studies on gene-gene interactions suggest that single nucleotide
polymorphisms in one gene may affect expression of other genes. The current study
aims to explore the role of CYP19A1 single nucleotide polymorphisms on CYP19A1,
NFkappaB1 and IL6 gene expression. METHODS: Phenotype-genotype associations,
cross-associations between genes, and haplotype analyses were performed in both
normal human colon (n=82) and liver (n=238) samples. RESULTS: CYP19A1 rs10459592,
rs1961177, and rs6493497 were associated with CYP19A1 expression in colon samples
(P=0.042, P=0.041, and P=0.013, respectively). CYP19A1 single nucleotide
polymorphisms (rs12908960, rs730154, rs8025191, and rs17523880) were correlated
with NFkappaB1 expression (P=0.047, P=0.04, P=0.05, and P=0.03, respectively),
and CYP19A1 rs11856927, rs2470152, and rs2470144 (P=0.049, P=0.025, P=0.047,
respectively) were associated with IL6 expression in the colon. While rs730154
and rs17523880 could not be analyzed in the liver samples, none of the other
associations with the colon were replicated in the liver samples. Haplotype
analysis revealed three separate haplotypes of the CYP19A1 single nucleotide
polymorphism that were significantly associated with CYP19A1, NFkappaB1, and IL6
gene expression. CONCLUSION: CYP19A1 single nucleotide polymorphisms are
associated not only with CYP19A1 expression but also with NFkappaB1 and IL6
expression. These data demonstrate the possible functional consequences of
genetic variation within the CYP19A1 gene on other genes in a biologically
plausible pathway.
PMID- 25114583
TI - An infant with poor weight gain and hypochloremic metabolic alkalosis: a case
report.
AB - Bartter syndrome is an autosomal recessive disease manifested by a defect in
chloride transport in the thick loop of Henle, with different genetic origins and
molecular pathophysiology. Children with Bartter syndrome generally present in
early infancy with persistent polyuria and associated dehydration, electrolyte
imbalance, and failure to thrive. Although early diagnosis and appropriate
treatment of Bartter syndrome may improve the outcome, some children will
progress to renal failure. We report a case of an 8-week-old infant who was
admitted for electrolyte imbalance and failure to thrive. Laboratory studies
revealed hypochloremic metabolic alkalosis with severe hypokalemia. Health care
providers should consider Bartter syndrome when excessive chloride losses appear
to be renal in origin and the patient has normal blood pressure and high levels
of serum renin and aldosterone. Treatments, including indomethacin,
spironolactone, and aggressive fluid and electrolyte replacement, may prevent
renal failure in children with Bartter syndrome. Molecular genetics studies are
indicated to identify the primary genetic defect.
PMID- 25114584
TI - An open-label, long-term study examining the safety and tolerability of
pregabalin in Japanese patients with central neuropathic pain.
AB - PURPOSE: Studies of pregabalin for the treatment of central neuropathic pain have
been limited to double-blind trials of 4-17 weeks in duration. The purpose of
this study was to assess the long-term safety and tolerability of pregabalin in
Japanese patients with central neuropathic pain. The efficacy of pregabalin was
also assessed as a secondary measure. PATIENTS AND METHODS: This was a 53-week,
multicenter, open-label trial of pregabalin (150-600 mg/day) in Japanese patients
with central neuropathic pain due to spinal cord injury, multiple sclerosis, or
cerebral stroke. RESULTS: A total of 103 patients received pregabalin (post
stroke =60; spinal cord injury =38; and multiple sclerosis =5). A majority of
patients (87.4%) experienced one or more treatment-related adverse events, most
commonly somnolence, weight gain, dizziness, or peripheral edema. The adverse
event profile was similar to that seen in other indications of pregabalin. Most
treatment-related adverse events were mild (89.1%) or moderate (9.2%) in
intensity. Pregabalin treatment improved total score, sensory pain, affective
pain, visual analog scale (VAS), and present pain intensity scores on the Short
Form McGill Pain Questionnaire (SF-MPQ) and ten-item modified Brief Pain
Inventory (mBPI-10) total score at endpoint compared with baseline. Improvements
in SF-MPQ VAS and mBPI-10 total scores were evident in all patient
subpopulations. Mean changes from baseline in SF-MPQ VAS and mBPI-10 scores at
endpoint were -20.1 and -1.4, respectively. CONCLUSION: These findings
demonstrate that pregabalin is generally well tolerated and provides sustained
efficacy over a 53-week treatment period in patients with chronic central
neuropathic pain.
PMID- 25114582
TI - MicroRNA binding site polymorphisms as biomarkers in cancer management and
research.
AB - MicroRNAs (miRNAs) are important regulators of eukaryotic gene expression. They
have been implicated in a broad range of biological processes, and miRNA-related
genetic alterations probably underlie several human diseases. Single nucleotide
polymorphisms of transcripts may modulate the posttranscriptional regulation of
gene expression by miRNAs and explain interindividual variability in cancer risk
and in chemotherapy response. On the basis of recent association studies
published in the literature, the present review mainly summarizes the potential
role of miRNAs as molecular biomarkers for disease susceptibility, diagnosis,
prognosis, and drug-response prediction in tumors. Many clues suggest a role for
polymorphisms within the 3' untranslated regions of KRAS rs61764370, SET8
rs16917496, and MDM4 rs4245739 as SNPs in miRNA binding sites highly promising in
the biology of human cancer. However, more studies are needed to better
characterize the composite spectrum of genetic determinants for future use of
markers in risk prediction and clinical management of diseases, heading toward
personalized medicine.
PMID- 25114585
TI - Challenges in the development of future treatments for breast cancer stem cells.
AB - The recurrence of tumors after years of disease-free survival has spurred
interest in the concept that cancers may have a stem cell basis. Current
speculation holds that as few as 0.1% of the tumor mass may be chemoresistant and
radioresistant, harboring stem-like properties that drive tumor survival,
development, and metastasis. There are intense investigations to characterize
cancer stem cells on the basis of self-renewal and multi-lineage differentiation.
Thus far, no successful targeted therapies have been developed and reached the
clinic, but as these cells are isolated and characterized, insights may be
unraveled. In this review, we discuss the controversy over the origins of the
cancer stem cell hypothesis and the unforeseen factors that may facilitate breast
cancer stem cell survival and metastasis. We discuss the role of tumor
microenvironment, including carcinoma-associated fibroblasts, epigenetic factors,
and the Th1/Th2 balance, in supporting breast cancer stem cells. In addition, we
have incorporated ideas on the epithelial-to-mesenchymal transition in metastatic
dissemination of epithelial malignancies. This area is relevant since breast
cancer stem cells have been suggested to revert to a mesenchymal phenotype during
the progression of cancer. Finally we discuss prospects of developing targeted
therapy including novel treatment modalities such as oncolytic viral therapy,
differentiation therapy, and nanotechnology.
PMID- 25114588
TI - Role of trastuzumab emtansine in the treatment of HER2-positive breast cancer.
AB - Trastuzumab is a monoclonal antibody that is used in the treatment of breast
cancer. Trastuzumab targets the human epidermal growth factor receptor 2 (HER2)
receptor on breast cancer cells that express this tyrosine kinase receptor. These
cancers are referred to as HER2-positive breast cancer. The original studies of
trastuzumab showed improved survival in metastatic breast cancer; however,
resistance often develops. In the adjuvant setting, women often progress despite
therapy that includes trastuzumab. Antibody-drug conjugates are a new class of
powerful drugs designed to target high-dose chemotherapy directly to the cancer
cells. Trastuzumab emtansine is one of these antibody-drug conjugates and was the
first Food and Drug Administration approved drug for a solid tumor. Emtansine is
a potent antimicrotubule agent. Trastuzumab is used to target this potent
chemotherapy agent directly to the HER2-expressing cancer cells. This review
article will summarize the evidence from the preclinical studies, summarize
evidence from the clinical trials, discuss current clinical trials, discuss
current approval of trastuzumab emtansine, and discuss future directions of
research.
PMID- 25114587
TI - Preserving fertility in patients undergoing treatment for breast cancer: current
perspectives.
AB - Invasive breast cancer (BC) is the most frequent cancer of young women.
Considering the trend toward postponing childbearing until the later reproductive
years, the number of childless women at diagnosis of BC will continue to
increase. The American Society of Clinical Oncology and the American Society for
Reproductive Medicine have recommended that the impact of cancer treatments on
fertility should be addressed with all cancer patients of reproductive age and
that options for fertility preservation, such as cryopreservation of embryos and
oocytes, ovarian tissue, in vitro maturation of immature oocytes, and ovarian
suppression with gonadotropin-releasing hormone analogs, should be discussed
routinely. To optimally counsel patients on how to best weigh the risks and
benefits of fertility preservation, both the health care provider and the patient
must know about the options, their risks, and their likelihood of success. The
aim of this review is to summarize current knowledge on fertility preservation
options for young BC patients, surrogates of ovarian function, psychosocial
aspects of infertility after cancer treatment, women's attitudes towards
childbearing after cancer treatment, and health care providers' attitudes towards
fertility preservation.
PMID- 25114589
TI - Barrier protective use of skin care to prevent chemotherapy-induced cutaneous
symptoms and to maintain quality of life in patients with breast cancer.
AB - PURPOSE: Chemotherapy with anthracyclines, taxanes, or alkylating agents often
causes cutaneous side effects. Nonspecific inhibition of the proliferative
activity of keratinocytes has antidifferentiation effects that lead to defects in
the barrier function and, thus, to dry, itchy, and irritable skin. These
cutaneous symptoms reduce the quality of life of the patients considerably.
Conditioning with topical application of niacinamide uses the cytoprotective and
barrier stabilizing effect of vitamin B3. PATIENTS AND METHODS: A multicenter
randomized crossover study investigated the influence of the test preparation on
the quality of life compared to standard care for 73 patients with breast cancer
undergoing adjuvant or neoadjuvant cytostatic therapy. Primary target parameter
was the Dermatology Life Quality Index with its respective subscales after 6
weeks of a twice-daily application of the respective preparations. Additionally,
specific symptoms such as pruritus, dryness, and irritability have been assessed
using visual analog scales. RESULTS: Regarding the total score of the Dermatology
Life Quality Index, no relevant differences could be observed. However, the
results for the "symptoms and feelings" subscale show a significant advantage in
favor of the test preparation. Significant superiority of the test preparation
could also be observed in the secondary target parameters, the visual analog
scales (P<0.05). CONCLUSION: The results show for the first time a significant
superiority of prophylactic application of niacinamide for maintaining quality of
life while undergoing cytostatic treatment.
PMID- 25114586
TI - Candidate prognostic markers in breast cancer: focus on extracellular proteases
and their inhibitors.
AB - The extracellular matrix (ECM) is the complex network of proteins that surrounds
cells in multicellular organisms. Due to its diverse nature and composition, the
ECM has a multifaceted role in both normal tissue homeostasis and
pathophysiology. It provides structural support, segregates tissues from one
another, and regulates intercellular communication. Furthermore, the ECM
sequesters a wide range of growth factors and cytokines that may be released upon
specific and well-coordinated cues. Regulation of the ECM is performed by the
extracellular proteases, which are tasked with cleaving and remodeling this
intricate and diverse protein matrix. Accordingly, extracellular proteases are
differentially expressed in various tissue types and in many diseases such as
cancer. In fact, metastatic dissemination of tumor cells requires degradation of
extracellular matrices by several families of proteases, including
metalloproteinases and serine proteases, among others. Extracellular proteases
are emerging as strong candidate cancer biomarkers for aiding and predicting
patient outcome. Not surprisingly, inhibition of these protumorigenic enzymes in
animal models of metastasis has shown impressive therapeutic effects. As such,
many of these proteolytic inhibitors are currently in various phases of clinical
investigation. In addition to direct approaches, aberrant expression of
extracellular proteases in disease states may also facilitate the selective
delivery of other therapeutic or imaging agents. Herein, we outline extracellular
proteases that are either bona fide or probable prognostic markers in breast
cancer. Furthermore, using existing patient data and multiple robust statistical
analyses, we highlight several extracellular proteases and associated inhibitors
(eg, uPA, ADAMs, MMPs, TIMPs, RECK) that hold the greatest potential as clinical
biomarkers. With the recent advances in high-throughput technology and targeted
therapies, the incorporation of extracellular protease status in breast cancer
patient management may have a profound effect on improving outcomes in this
deadly disease.
PMID- 25114590
TI - The epidemiology of Sjogren's syndrome.
AB - Sjogren's syndrome is a chronic systemic autoimmune disease characterized by
lymphocytic infiltration of exocrine glands. It can present as an entity by
itself, primary Sjogren's syndrome (pSS), or in addition to another autoimmune
disease, secondary Sjogren's syndrome (sSS). pSS has a strong female propensity
and is more prevalent in Caucasian women, with the mean age of onset usually in
the 4th to 5th decade. Clinical presentation varies from mild symptoms, such as
classic sicca symptoms of dry eyes and dry mouth, keratoconjunctivitis sicca, and
xerostomia, to severe systemic symptoms, involving multiple organ systems.
Furthermore, a range of autoantibodies can be present in Sjogren's syndrome (anti
SSA/Ro and anti-SSB/La antibodies, rheumatoid factor, cryoglobulins, antinuclear
antibodies), complicating the presentation. The heterogeneity of signs and
symptoms has led to the development of multiple classification criteria. However,
there is no accepted universal classification criterion for the diagnosis of
Sjogren's syndrome. There are a limited number of studies that have been
published on the epidemiology of Sjogren's syndrome, and the incidence and
prevalence of the disease varies according to the classification criteria used.
The data is further confounded by selection bias and misclassification bias,
making it difficult for interpretation. The aim of this review is to understand
the reported incidence and prevalence on pSS and sSS, the frequency of
autoantibodies, and the risk of malignancy, which has been associated with pSS,
taking into account the different classification criteria used.
PMID- 25114591
TI - A comparison of the treatment effects of the Forsus Fatigue Resistance Device and
the Twin Block appliance in patients with class II malocclusions.
AB - OBJECTIVES: We evaluated the skeletal and dentoalveolar effects of the Forsus
Fatigue Resistance Device (FRD) and the Twin Block appliance (TB) in comparison
with nontreated controls in the treatment of patients with class II division 1
malocclusion. MATERIALS AND METHODS: THIS RETROSPECTIVE STUDY INCLUDED THREE
GROUPS: TB (n=37; mean age, 11.2 years), FRD (n=30; mean age, 12.9 years), and
controls (n=25; mean age, 12.6 years). Lateral cephalograms were evaluated at T1
(pretreatment) and at T2 (postappliance removal/equivalent time frame in
controls). Cephalometric changes were evaluated using the Clark analysis,
including 27 measurements. RESULTS: Sagittal correction of class II malocclusion
appeared to be mainly achieved by dentoalveolar changes in the FRD group. The TB
was able to induce both skeletal and dentoalveolar changes. A favorable influence
on facial convexity was achieved by both groups. Significant upper incisor
retroclination occurred with the TB (-12.42 degrees ), whereas only -4 degrees
was observed in the FRD group. The lower incisors proclined more in the FRD group
than the TB group. Incisor overjet reduction was 62% in the TB group versus 56%
in the FRD group. Molar relation was corrected in both functional groups,
resulting in a class I relation, although no change appeared in the control
sample. CONCLUSION: Both appliances were effective in correcting the class II
malocclusion. Both the FRD and the TB induced significant maxillary and
mandibular dentoalveolar changes; skeletal changes were induced by TB but not FRD
therapy.
PMID- 25114592
TI - Arguments for and against HIV self-testing.
AB - Approximately 60% of human immunodeficiency virus (HIV)-infected individuals are
unaware of their infection, and stigma and discrimination continue to threaten
acceptance of HIV testing services worldwide. Self-testing for HIV has garnered
controversy for years and the debate reignited with the approval of a point-of
care test for over-the-counter sale in the US in 2012. Here, we present arguments
for and against HIV self-testing. The case in support of HIV self-testing
contends that: the modality is highly acceptable, especially among the most at
risk individuals; self-testing empowers users, thus helping to normalize testing;
and mutual partner testing has the potential to increase awareness of risk and
avert condomless sex between discordant partners. Arguments against HIV self
testing include: cost limits access to those who need testing most; false
negative results, especially during the window period, may lead to false
reassurance and could promote sex between discordant partners at the time of
highest infectivity; opportunities for counseling, linkage to care, and diagnosis
of other sexually transmitted infections may be missed; and self-testing leads to
potential for coercion between partners. Research is needed to better define the
risks of self-testing, especially as performance of the assays improves, and to
delineate the benefits of programs designed to improve access to self-test kits,
because this testing modality has numerous potential advantages and drawbacks.
PMID- 25114593
TI - Risk management of seasonal influenza during pregnancy: current perspectives.
AB - Influenza poses unique risks to pregnant women, who are particularly susceptible
to morbidity and mortality. Historically, pregnant women have been
overrepresented among patients with severe illness and complications from
influenza, and have been more likely to require hospitalization and intensive
care unit admission. An increased risk of adverse outcomes is also present for
fetuses/neonates born to women affected by influenza during pregnancy. These
risks to mothers and babies have been observed during both nonpandemic and
pandemic influenza seasons. During the H1N1 influenza pandemic of 2009-2010,
pregnant women were more likely to be hospitalized or admitted to intensive care
units, and were at higher risk of death compared to nonpregnant adults.
Vaccination remains the most effective intervention to prevent severe illness,
and antiviral medications are an important adjunct to ameliorate disease when it
occurs. Unfortunately, despite national guidelines recommending universal
vaccination for women who are pregnant during influenza season, actual
vaccination rates do not achieve desired targets among pregnant women. Pregnant
women are also sometimes reluctant to use antiviral medications during pregnancy.
Some of the barriers to use of vaccines and medications during pregnancy are a
lack of knowledge of recommendations and of safety data. By improving knowledge
and understanding of influenza and vaccination recommendations, vaccine
acceptance rates among pregnant women can be improved. Currently, the appropriate
use of vaccination and antiviral medications is the best line of defense against
influenza and its sequelae among pregnant women, and strategies to increase
acceptance are crucial. This article will review the importance of influenza in
pregnancy, and discuss vaccination and antiviral medications for pregnant women.
PMID- 25114595
TI - Correlation between MRI results and intraoperative findings in patients with
silicone breast implants.
AB - BACKGROUND: Silicone gel breast implants may silently rupture without detection.
This has been the main reason for magnetic resonance imaging (MRI) of the
augmented or reconstructed breast. The aim of the present study was to
investigate the accuracy of MRI for implant rupture. METHODS: Fifty consecutive
patients with 85 silicone gel implants were included in the study. The mean age
of the patients was 51 (range 21-72) years, with a mean duration of implantation
of 3.8 (range 1-28) years. All patients underwent clinical examination and breast
MRI. Intraoperative implant rupture was diagnosed by the operating surgeon.
RESULTS: Nineteen of the 50 patients suffered from clinical symptoms. An implant
rupture was diagnosed by MRI in 22 of 85 implants (26%). In seven of 17 removed
implants (41%), the intraoperative diagnosis corresponded with the positive MRI
result. However, only 57% of these patients were symptomatic. Ultrasound imaging
of the harvested implants showed signs of interrupted inner layers of the implant
despite integrity of the outer shell. By microsurgical separation of the
different layers of the implant shell, we were able to reproduce this phenomenon
and to produce signs of implant rupture on MRI. CONCLUSION: Our results show that
rupture of only the inner layers of the implant shell with integrity of the outer
shell leads to a misdiagnosis on MRI. Correlation with clinical symptoms and the
specific wishes of the patient should guide the indication for implant removal.
PMID- 25114596
TI - Idiopathic CD4+ lymphocytopenia in Hispanic male: case report and literature
review.
AB - INTRODUCTION: Idiopathic cluster of differentiation 4 (CD4+) T-cell
lymphocytopenia (ICL) is a rare non human immunodeficiency virus (HIV)-related
syndrome with unclear natural history and prognosis that was first reported and
defined in 1992. ICL has been observed in patients after the onset of an
opportunistic infection without known immunosuppression. CASE PRESENTATION: A 20
year-old Hispanic male patient without significant past medical history presented
with progressive shortness of breath and cough for 3 weeks. Chest computed
tomography showed bilateral cavitary lesions in the upper lung lobes. The HIV
rapid screening test as well as the sputum acid-fast bacilli test were both
positive. The patient was started on antituberculosis therapy. The CD4 count was
noticed to be low. However, the HIV Western blot test was negative, and the HIV
viral load was within normal limit. Further radiologic studies, hemato-oncologic,
and autoimmune workups were normal. The patient was discharged on the treatment
for tuberculosis. Follow-up after 8 weeks revealed a persistent low CD4+ count,
and the repeated HIV tests were negative. CONCLUSION: The clinical features of
ICL range from an asymptomatic condition to life-threatening complications that
imitate the clinical course of HIV-infected patients. The differential diagnosis
in adults comprises primarily HIV infection and other diseases or drug side
effects. ICL is very rare and should be considered in the absence of any defined
immunodeficiency or therapy associated with depressed levels of CD4+ T-cells.
Early detection and recognition of the disease allow purposeful and systemic
treatment approach and screening for the affected patients.
PMID- 25114594
TI - Preserving fertility in young patients with endometrial cancer: current
perspectives.
AB - Endometrial cancer (EC) is the most common gynecologic malignancy in developed
countries and affects predominantly postmenopausal women. It is estimated,
however, that 15%-25% of women will be diagnosed before menopause. As more women
choose to defer childbearing until later in life, the feasibility and safety of
fertility-sparing EC management have been increasingly studied. Definitive
treatment of total hysterectomy and bilateral salpingo-oophorectomy precludes
future fertility and may thus be undesirable by women who wish to maintain their
reproductive potential. However, the consideration of conservative management
carries the oncologic risks of unstaged EC and the risk of missing a synchronous
ovarian cancer. It is further complicated by the lack of consensus regarding the
initial assessment, treatment, and surveillance. Conservative treatment with
progestins has been shown to be a feasible and safe fertility-sparing approach
for women with low grade, early stage EC with no myometrial invasion. The two
most commonly adopted regimens are medroxyprogesterone acetate at 500-600 mg
daily and megestrol acetate at 160 mg daily for a minimum of 6-9 months, with
initial response rates commonly reported between 60% and 80% and recurrence rates
between 25% and 40%. Photodynamic therapy and hysteroscopic EC excision have
recently been reported as alternative approaches to progestin therapy alone.
However, limited efficacy and safety data exist. Live birth rates after progestin
therapy have typically been reported around 30%; however, when focusing only on
those who do pursue fertility after successful treatment, the live birth rates
were found to be higher than 60%. Assisted reproductive technology has been
associated with a higher live birth rate compared with spontaneous conception,
most likely reflecting the presence of infertility at baseline. Close follow-up
is of paramount importance, and definitive treatment after completion of
childbearing is advised.
PMID- 25114597
TI - Differential renal adverse effects of ibuprofen and indomethacin in preterm
infants: a review.
AB - OBJECTIVE: The objective of this study was to evaluate the extent of renal
adverse effects caused by ibuprofen or indomethacin in order to choose the safer
drug to administer to preterm infants. METHODS: THE FOLLOWING THREE PARAMETERS OF
RENAL FUNCTION WERE TAKEN INTO CONSIDERATION: 1) the urine output; 2) the serum
creatinine concentration; and 3) the frequency of oliguria. The bibliographic
search was performed using PubMed and Embase databases as search engines.
RESULTS: Urine output ranged from 3.5+/-1.2 to 4.0+/-1.4 mL/kg/h after ibuprofen
treatment, and from 2.8+/-1.1 to 3.6+/-1.4 mL/kg/h after indomethacin treatment.
The values for ibuprofen are significantly (P<0.05) higher than those for
indomethacin. The serum creatinine concentrations ranged from 0.98+/-0.24 to
1.48+/-0.2 mg/dL after ibuprofen treatment, and from 1.06+/-0.24 and 2.03+/-2.10
mg/dL after indomethacin treatment. The values for ibuprofen are significantly
(P<0.05) lower than those for indomethacin. The frequency of oliguria ranged from
1.0% to 9.6% (ibuprofen) and from 14.8% to 40.0% (indomethacin), and was
significantly lower following ibuprofen than indomethacin administration. In
infants with body weight lower than 1,000 g, oliguria appeared in 5% (ibuprofen)
and 40% (indomethacin; P=0.02). CONCLUSION: Indomethacin is associated with more
severe renal adverse effects than ibuprofen. Ibuprofen is less nephrotoxic than
indomethacin and should be used to treat patent ductus arteriosus in preterm
infants. Immaturity increases the frequency of adverse effects of indomethacin.
PMID- 25114598
TI - Evaluation of the angled Episcissors-60((r)) episiotomy scissors in spontaneous
vaginal deliveries.
AB - BACKGROUND: Obstetric anal sphincter injuries (OASIs) are the leading cause of
anal incontinence in women. Episiotomies with a postdelivery suture angle of less
than 30 degrees to the midline are more likely to injure the anal sphincter
directly, while those with a suture angle of more than 60 degrees are associated
with increased incidence of OASIs, as they do not relieve the pressure on the
perineum. A safe zone of 40 degrees -60 degrees has been proposed. Recently, two
new types of episiotomy scissors (Episcissors-60((r)) Straight version and angled
version) were introduced to ensure a standardized cutting angle of 60 degrees to
the midline. We audited our results with the angled Episcissors-60 in spontaneous
vaginal deliveries. MATERIALS AND METHODS: Consecutive patients delivering in two
private maternity hospitals in Thane, India undergoing clinically indicated
episiotomies were included. Only patients delivering spontaneously were included.
The scissors were introduced vaginally at crowning, and aligned to orient the
guide limb vertically from the posterior fourchette to the anus. While a single
cut was preferred, a stagger cut was needed for some women. Postdelivery angles
were measured by placing a protractor transparency on the perineum after delivery
and marking the angle with an indelible ink pen. Per rectal examination was
performed prior to suturing to detect OASIs. RESULTS: A total of 25 women
underwent clinically indicated episiotomies. Of these, 16 women were nulliparous,
eight women were para 1, and one woman was a para 2. One woman had a vaginal
breech delivery (para 2), and the rest were cephalic vertex deliveries. The
average age was 27 (range 20-35) years. The median birth weight was 2,800 g
(standard deviation 312 g, interquartile range 2,500-3,000 g). The median
postdelivery suture angle of the episiotomy was 50 degrees (standard deviation
3.5 degrees , interquartile range 48 degrees -54 degrees , range 45 degrees -55
degrees ). No cases of OASI were detected in this series. CONCLUSION: The
Episcissors-60 angled version demonstrated a postdelivery suture angle of 50
degrees in a cohort of Indian women undergoing spontaneous vaginal deliveries.
PMID- 25114599
TI - Laser speckle contrast imaging for intraoperative assessment of liver
microcirculation: a clinical pilot study.
AB - BACKGROUND: Liver microcirculation can be affected by a wide variety of causes
relevant to liver transplantation and resectional surgery. Intraoperative
assessment of the microcirculation could possibly predict postoperative outcome.
The present pilot study introduces laser speckle contrast imaging (LSCI) as a new
clinical method for assessing liver microcirculation. METHODS: LSCI measurements
of liver microcirculation were performed on ten patients undergoing liver
resection. Measurements were made during apnea with and without liver blood
inflow occlusion. Hepatic blood flow was assessed by subtracting zero inflow
signal from the total signal. Zero inflow signal was obtained after hepatic
artery and portal vein occlusion. Perfusion was expressed in laser speckle
perfusion units, and intraindividual and interindividual variability in liver
perfusion was investigated using the coefficient of variability. RESULTS: Hepatic
microcirculation measurements were successfully made in all patients resulting in
analyzable speckle contrast images. Mean hepatic blood flow was 410+/-36 laser
speckle perfusion units. Zero inflow signal amounted to 40%+/-4% of the total
signal. Intraindividual and interindividual coefficients of variability in liver
perfusion were 25% and 28%, respectively. CONCLUSION: Under the conditions of
this pilot study, LSCI allows rapid noncontact measurements of hepatic blood
perfusion over wide areas. More studies are needed on methods of handling
movement artifacts.
PMID- 25114600
TI - Sealing vessels up to 7 mm in diameter solely with ultrasonic technology.
AB - INTRODUCTION: Ultrasonic energy is a mainstay in the armamentarium of surgeons,
providing multifunctionality, precision, and control when dissecting and sealing
vessels up to 5 mm in diameter. Historically, the inability to seal vessels in
the 5-7 mm range has been perceived as an inherent limitation of ultrasonic
technology. The purpose of this study was to evaluate sealing of vessels up to 7
mm in diameter with an ultrasonic device that modulates energy delivery during
the sealing period. METHODS: In ex vivo benchtop and in vivo acute and survival
preclinical models, a new ultrasonic device, Harmonic ACE((r))+7 Shears (Harmonic
7), was compared with advanced bipolar devices in sealing vessels 1-7 mm in
diameter with respect of burst pressure, seal reliability, and seal durability.
Lateral thermal damage and transection time were also evaluated. RESULTS: Ex vivo
tests of Harmonic 7 demonstrated significantly greater median burst pressures
than an advanced bipolar device both for vessels <5 mm in diameter (1,078 mmHg
and 836 mmHg, respectively, P=0.046) and for those in the range of 5-7 mm (1,419
mmHg and 591 mmHg, P<0.001). In vivo tests in porcine and caprine models
demonstrated similar rates of hemostasis between Harmonic 7 and advanced bipolar
devices, with high success rates at initial transection and seal durability of
100% after a 30-day survival period. CONCLUSION: Sealing 5-7 mm vessels is not a
limitation of the type of energy used but of how energy is delivered to tissue.
These studies document the ability of ultrasonic energy alone to reliably seal
large vessels 5-7 mm in diameter, with significantly greater burst pressure
observed in in vitro studies than those observed with an advanced bipolar
technology when energy delivery is modulated during the sealing cycle.
Furthermore, the seals created in 5-7 mm vessels are shown to be reliable and
durable in in vivo preclinical studies.
PMID- 25114603
TI - Transarterial chemoembolization using iodized oil for unresectable hepatocellular
carcinoma: perspective from multistep hepatocarcinogenesis.
AB - Transarterial chemoembolization (TACE) using iodized oil (Lipiodol((r))) (Lp
TACE) as a carrier of chemotherapeutic agents has been routinely performed to
control hepatocellular carcinomas (HCC) in Japan, and its use has yielded fairly
beneficial therapeutic results. Lipiodol is thought to pass through the tumor
sinusoids of HCC and reach the outflow drainage areas, namely, the portal venous
side of the tumor. By doing this, Lipiodol blocks not only the tumor's arterial
inflow but also its portal venous outflow, providing sufficient ischemic effects.
It is known that the inflow blood system, tumor sinusoids, and outflow blood
system change drastically during the process of multistep hepatocarcinogenesis;
thus, it is reasonable to postulate that the distribution of Lipiodol and the
subsequent therapeutic effect of Lp-TACE may also change during that process.
Arterial inflow to HCC is highest for moderately differentiated HCC (mHCC) and is
relatively low in well or poorly differentiated HCC (wHCC and pHCC,
respectively). It has been suggested that the metabolic state of wHCC and mHCC is
aerobic, while that of pHCC is anaerobic. The tumor sinusoids in wHCC and mHCC
are small in size and large in number, while those in pHCC are large in size and
small in number. This finding results in a greater chance of tumor cell exposure
to chemotherapeutic agents in the former and a lesser chance in the latter. The
outflow tract, namely, the drainage system via the residual portal venous
branches within the pseudocapsule, is more complete in mHCC and pHCC and less so
in wHCC. Considering all of these components of HCC of different histological
grades, Lp-TACE should have the greatest effect on mHCC and a relatively low
effect on wHCC and pHCC. To achieve consistently high therapeutic results, it is
important to consider these components, which affect the sensitivity of HCC to Lp
TACE, to maximize both the chemotherapeutic and ischemic effects of this therapy.
PMID- 25114602
TI - Ending hepatitis C in the United States: the role of screening.
AB - The US faces at least two distinct epidemics of hepatitis C virus infection
(HCV), and due largely to revised screening recommendations and novel therapeutic
agents, corresponding opportunities. As only 49%-75% of HCV-infected persons in
the US are aware of their infection, any chance of addressing HCV in the US is
dependent upon screening to identify undiagnosed infections. Most HCV in the US
consists of longstanding infections among persons born during 1945-1965 who are
suffering escalating rates of liver-related morbidity and mortality. Mathematical
modeling supports aggressive action to reach and treat these persons to minimize
the subsequent burden of advanced liver disease on patients and the health care
system. Incident infection is primarily among persons who inject drugs, less than
10% of whom have been treated for HCV. Expanded screening and treatment of active
persons who inject drugs raises the prospect of utilizing "treatment as
prevention" to stem the tide of incident HCV infections in this population. HIV
positive men who have sex with men (MSM) represent a population at risk for
sexually transmitted HCV who may also benefit from adjusted screening guidelines
to identify both acute and chronic infections. Prisoners also represent a
critical population for aggressive screening and treatment. Finally, the two
stage testing algorithm for HCV diagnosis is problematic and difficult for
patients and providers to navigate. While emerging therapeutics raise the
prospect of reducing HCV-related morbidity and mortality, as well as eliminating
new infections, major barriers remain with regard to identifying infections,
improving access to treatment, and ensuring payer coverage of costly new
therapeutic regimens.
PMID- 25114601
TI - Pharmacogenetics of hepatitis C: transition from interferon-based therapies to
direct-acting antiviral agents.
AB - Hepatitis C virus (HCV) has emerged as a major viral pandemic over the past two
decades, infecting 170 million individuals, which equates to approximately 3% of
the world's population. The prevalence of HCV varies according to geographic
region, being highest in developing countries such as Egypt. HCV has a high
tendency to induce chronic progressive liver damage in the form of hepatic
fibrosis, cirrhosis, or liver cancer. To date, there is no vaccine against HCV
infection. Combination therapy comprising PEGylated interferon-alpha and
ribavirin has been the standard of care for patients with chronic hepatitis C for
more than a decade. However, many patients still do not respond to therapy or
develop adverse events. Recently, direct antiviral agents such as protease
inhibitors, polymerase inhibitors, or NS5A inhibitors have been used to augment
PEGylated interferon and ribavirin, resulting in better efficacy, better
tolerance, and a shorter treatment duration. However, most clinical trials have
focused on assessing the efficacy and safety of direct antiviral agents in
patients with genotype 1, and the response of other HCV genotypes has not been
elucidated. Moreover, the prohibitive costs of such triple therapies will limit
their use in patients in developing countries where most of the HCV infection
exists. Understanding the host and viral factors associated with viral clearance
is necessary for individualizing therapy to maximize sustained virologic response
rates, prevent progression to liver disease, and increase the overall benefits of
therapy with respect to its costs. Genome wide studies have shown significant
associations between a set of polymorphisms in the region of the interleukin-28B
(IL28B) gene and natural clearance of HCV infection or after PEGylated interferon
alpha and ribavirin treatment with and without direct antiviral agents. This
paper synthesizes the recent advances in the pharmacogenetics of HCV infection in
the era of triple therapies.
PMID- 25114604
TI - Transtendon rotator-cuff repair of partial-thickness articular surface tears can
lead to medial rotator-cuff failure.
AB - PURPOSE: The purpose of this study was to evaluate clinical and anatomic outcomes
of patients following transtendon rotator-cuff repair of partial articular
supraspinatus tendon avulsion (PASTA) lesions. PATIENTS AND METHODS: Patients in
the senior author's practice who had isolated PASTA lesions treated by
transtendon rotator-cuff repair were included (n=8) and retrospectively reviewed.
All patients were evaluated preoperatively and at a mean of 21.2 months (+/-9.7
months) postoperatively using standardized clinical evaluation (physical exam,
American Shoulder and Elbow Surgeons, and Simple Shoulder Test). All patients
underwent postoperative imaging with a magnetic resonance imaging arthrogram.
RESULTS: There was a significant improvement in American Shoulder and Elbow
Surgeons (42.7+/-17.5 to 86.9+/-25.2) and Simple Shoulder Test (4.6+/-3.2 to
10.1+/-3.8) scores from pre- to postoperative, respectively. Postoperative
imaging demonstrated full-thickness medial cuff tearing in seven patients, and
one patient with a persistent partial articular surface defect. CONCLUSION:
Transtendon repair of PASTA lesions may lead to improvements in clinical outcome.
However, postoperative imaging demonstrated a high incidence of full-thickness
rotator-cuff defects following repair.
PMID- 25114605
TI - Sex difference in top performers from Ironman to double deca iron ultra
triathlon.
AB - This study investigated changes in performance and sex difference in top
performers for ultra-triathlon races held between 1978 and 2013 from Ironman (3.8
km swim, 180 km cycle, and 42 km run) to double deca iron ultra-triathlon
distance (76 km swim, 3,600 km cycle, and 844 km run). The fastest men ever were
faster than the fastest women ever for split and overall race times, with the
exception of the swimming split in the quintuple iron ultra-triathlon (19 km
swim, 900 km cycle, and 210.1 km run). Correlation analyses showed an increase in
sex difference with increasing length of race distance for swimming (r (2)=0.67,
P=0.023), running (r (2)=0.77, P=0.009), and overall race time (r (2)=0.77,
P=0.0087), but not for cycling (r (2)=0.26, P=0.23). For the annual top
performers, split and overall race times decreased across years nonlinearly in
female and male Ironman triathletes. For longer distances, cycling split times
decreased linearly in male triple iron ultra-triathletes, and running split times
decreased linearly in male double iron ultra-triathletes but increased linearly
in female triple and quintuple iron ultra-triathletes. Overall race times
increased nonlinearly in female triple and male quintuple iron ultra-triathletes.
The sex difference decreased nonlinearly in swimming, running, and overall race
time in Ironman triathletes but increased linearly in cycling and running and
nonlinearly in overall race time in triple iron ultra-triathletes. These findings
suggest that women reduced the sex difference nonlinearly in shorter ultra
triathlon distances (ie, Ironman), but for longer distances than the Ironman, the
sex difference increased or remained unchanged across years. It seems very
unlikely that female top performers will ever outrun male top performers in
ultratriathlons. The nonlinear change in speed and sex difference in Ironman
triathlon suggests that female and male Ironman triathletes have reached their
limits in performance.
PMID- 25114606
TI - Weight status and the perception of body image in men.
AB - Understanding the role of body size in relation to the accuracy of body image
perception in men is an important topic because of the implications for avoiding
and treating obesity, and it may serve as a potential diagnostic criterion for
eating disorders. The early research on this topic produced mixed findings. About
one-half of the early studies showed that obese men overestimated their body
size, with the remaining half providing accurate estimates. Later, improvements
in research technology and methodology provided a clearer indication of the role
of weight status in body image perception. Research in our laboratory has also
produced diverse findings, including that obese subjects sometimes overestimate
their body size. However, when examining our findings across several studies,
obese subjects had about the same level of accuracy in estimating their body size
as normal-weight subjects. Studies in our laboratory also permitted the
separation of sensory and nonsensory factors in body image perception. In all but
one instance, no differences were found overall between the ability of obese and
normal-weight subjects to detect overall changes in body size. Importantly,
however, obese subjects are better at detecting changes in their body size when
the image is distorted to be too thin as compared to too wide. Both obese and
normal-weight men require about a 3%-7% change in the width of their body size in
order to detect the change reliably. Correlations between a range of body mass
index values and body size estimation accuracy indicated no relationship between
these variables. Numerous studies in other laboratories asked men to place their
body size into discrete categorizes, ranging from thin to obese. Researchers
found that overweight and obese men underestimate their weight status, and that
men are less accurate in their categorizations than are women. Cultural
influences have been found to be important, with body size underestimations
occurring in cultures where a larger body is found to be desirable.
Methodological issues are reviewed with recommendations for future studies.
PMID- 25114609
TI - Examining the relationship between ethnicity and the use of drug-related
services: an ethnographic study of Nepali drug users in Hong Kong.
AB - A recent survey has shown that Nepali drug users in Hong Kong tend to have a low
rate of usage of day-care and residential rehabilitation services, but a high
rate of usage of methadone services. Little is known about the reasons behind
such a pattern. Therefore, in this study, a 12-month ethnographic examination has
been implemented in three sites, including a day-care center, residential
rehabilitation center, and methadone clinic, to explore the experiences of 20
Nepali drug users in their use of drug-related services in Hong Kong and to
examine the relationship between ethnicity and the use of drug-related services.
The result shows that the reason for this pattern of service use is related to
the approach of the services and the cultural perception of the service providers
about the service users. The day-care and residential rehabilitation services
emphasize an integrated approach, but the staff tend to overlook the
heterogeneity of their clients, for example, the differences in caste and sex,
and fail to provide suitable services to them, whereas the methadone service
follows a biomedical model, which seldom addresses the social characteristics of
the service users, which in turn minimizes the opportunity for misunderstandings
between the staff and the clients. This research shows that ethnicity is a
significant factor in drug treatment and that culture-specific treatment that
takes into consideration the treatment approach and the heterogeneity of the
clients is strongly needed.
PMID- 25114610
TI - Program- and service-level costs of seven screening, brief intervention, and
referral to treatment programs.
AB - This paper examines the costs of delivering screening, brief intervention, and
referral to treatment (SBIRT) services within the first seven demonstration
programs funded by the US Substance Abuse and Mental Health Services
Administration. Service-level costs were estimated and compared across
implementation model (contracted specialist, inhouse specialist, inhouse
generalist) and service delivery setting (emergency department, hospital
inpatient, outpatient). Program-level costs were estimated and compared across
grantee recipient programs. Service-level data were collected through timed
observations of SBIRT service delivery. Program-level data were collected during
key informant interviews using structured cost interview guides. At the service
level, support activities that occur before or after engaging the patient
comprise a considerable portion of the cost of delivering SBIRT services,
especially short duration services. At the program level, average costs decreased
as more patients were screened. Comparing across program and service levels, the
average annual operating costs calculated at the program level often exceeded the
cost of actual service delivery. Provider time spent in support of service
provision may comprise a large share of the costs in some cases because of
potentially substantial fixed and quasifixed costs associated with program
operation. The cost structure of screening, brief intervention, and referral to
treatment is complex and discontinuous of patient flow, causing annual operating
costs to exceed the costs of actual service provision for some settings and
implementation models.
PMID- 25114607
TI - The role of the monoamine oxidase A gene in moderating the response to adversity
and associated antisocial behavior: a review.
AB - Hereditary factors are increasingly attracting the interest of behavioral
scientists and practitioners. Our aim in the present article is to introduce some
state-of-the-art topics in behavioral genetics, as well as selected findings in
the field, in order to illustrate how genetic makeup can modulate the impact of
environmental factors. We focus on the most-studied polymorphism to date for
antisocial responses to adversity: the monoamine oxidase A gene. Advances,
caveats, and promises of current research are reviewed. We also discuss
implications for the use of genetic information in applied settings.
PMID- 25114611
TI - Expanding the National Drug Abuse Treatment Clinical Trials Network to address
the management of substance use disorders in general medical settings.
AB - The Patient Protection and Affordable Care Act (2010) and the Mental Health
Parity and Addiction Equity Act (2008) expand substance use disorder (SUD) care
services in the USA into general medical settings. Care offered in these settings
will engage substance-using patients in an integrated and patient-centered
environment that addresses physical and mental health comorbidities and follows a
chronic care model. This expansion of SUD services presents a great need for
evidence-based practices useful in general medical settings, and reveals several
research gaps to be addressed. The National Drug Abuse Treatment Clinical Trials
Network of the National Institute on Drug Abuse can serve an important role in
this endeavor. High-priority research gaps are highlighted in this commentary. A
discussion follows on how the National Drug Abuse Treatment Clinical Trials
Network can transform to address changing patterns in SUD care to efficiently
generate evidence to guide SUD treatment practice within the context of recent US
health care legislation.
PMID- 25114613
TI - Back from the brink - a note of thanks.
PMID- 25114612
TI - Patient registries for substance use disorders.
AB - This commentary discusses the need for developing patient registries of substance
use disorders (SUD) in general medical settings. A patient registry is a tool
that documents the natural history of target diseases. Clinicians and researchers
use registries to monitor patient comorbidities, care procedures and processes,
and treatment effectiveness for the purpose of improving care quality. Enactments
of the Affordable Care Act 2010 and the Mental Health Parity and Addiction Equity
Act 2008 open opportunities for many substance users to receive treatment
services in general medical settings. An increased number of patients with a wide
spectrum of SUD will initially receive services with a chronic disease management
approach in primary care. The establishment of computer-based SUD patient
registries can be assisted by wide adoption of electronic health record systems.
The linkage of SUD patient registries with electronic health record systems can
facilitate the advancement of SUD treatment research efforts and improve patient
care.
PMID- 25114614
TI - Pediatric facial transplantation: Ethical considerations.
AB - Facial transplantation is becoming increasingly accepted as a method of
reconstructing otherwise unreconstructable adult faces. As this modality is made
more available, we must turn our attention to pediatric patients who may benefit
from facial transplantation. In the current article, the authors present and
briefly examine the most pressing ethical challenges posed by the possibility of
performing facial transplantation on pediatric patients. Furthermore, they issue
a call for a policy statement on pediatric facial transplantation. The present
article may serve as a first step in that direction, highlighting ethical issues
that would need to be considered in the creation of such a statement.
PMID- 25114615
TI - Tracking the aesthetic outcomes of prosthetic breast reconstructions that have
complications.
AB - BACKGROUND: Aesthetic results following breast reconstruction have been shown to
be a major contributor to patient satisfaction. While many presume that
complications after reconstruction impact final aesthetic results, little data
exist to substantiate this putative relationship. OBJECTIVE: To track and
evaluate aesthetic outcomes following implant reconstructions with complications.
METHODS: A chart review was conducted on a series of consecutive expander-implant
breast reconstructions performed by the senior author between 2004 and 2012.
Included patients completed their prosthetic reconstruction or converted to
autologous methods and had a minimum follow-up period of 130 days. Four blinded
members of the division of plastic surgery independently rated postoperative
anterior photographs of patients' breasts using a validated scoring scale with
respect to five distinct aesthetic domains: breast mound volume, contour,
placement, scarring and inframammary fold. RESULTS: Of the 172 patients who met
the inclusion criteria, 36 experienced a complication. The tissue expander in one
half of these patients was salvaged and the remaining patients converted to
autologous reconstruction. The average aesthetic scores for each domain did not
differ significantly between patients who experienced a complication and retained
their expander and those who did not experience a complication. Patients who
converted to autologous tissue reconstruction after experiencing a complication
had the highest aesthetic scores. DISCUSSION: The ability to obtain aesthetic
results following a complication that were not statistically different from
results in those without complications may reflect the surgeon's refined attempt
to salvage the initial implant reconstruction; in other circumstances, the
improved cosmesis was achieved through conversion to an autologous tissue-based
method. CONCLUSION: The present study quantitatively assessed the impact of
complications on aesthetic outcomes following implant breast reconstruction.
Continuance of prosthetic reconstruction and conversion to autologous
reconstruction serve as viable options to obtain adequate aesthetic scores
following a complication. Information gained from the present analysis will help
manage patient expectations.
PMID- 25114616
TI - Are online learning modules an effective way to deliver hand trauma management
continuing medical education to emergency physicians?
AB - BACKGROUND: The enormity of modern medical knowledge and the rapidity of change
have created increased need for ongoing or continuing medical education (CME) for
physicians. Online CME is attractive for its availability at any time and any
place, low cost and potentially increased effectiveness compared with traditional
face-to-face delivery. OBJECTIVE: To determine whether online CME modules are an
effective method for delivering plastic surgery CME to primary care physicians.
METHODS: A needs assessment survey was conducted among all emergency and family
physicians in Nova Scotia. Results indicated that this type of program was
appealing, and that hand trauma related topics were most desired for CME. 7
Lesson Builder (SoftChalk LLC, www.softchalk.com) was used to construct a
multimedia e-learning module that was distributed along with a pretest, post-test
and feedback questionnaire. Quantitative (pre- and post-test scores) and
qualitative (feedback responses) data were analyzed. RESULTS: The 32 participants
who completed the study indicated that it was a positive and enjoyable
experience, and that there was a need for more resources like this. Compared with
pretest scores, there was a significant gain in knowledge following completion of
the module (P=0.001). CONCLUSION: The present study demonstrated that an e
learning format is attractive for this population and effective in increasing
knowledge. This positive outcome will lead to development of additional modules.
PMID- 25114617
TI - Early outcomes of arthroplasty of the first carpometacarpal joint using
pyrocarbon spherical implants.
AB - The first carpometacarpal joint (CMC) is the most common hand joint to develop
osteoarthritis. A survey found that many hand surgeons have revisited implant
arthroplasty because it preserves critical structures. However, there is
currently no implant with an ideal design and material composition. The present
study was the first to use and evaluate early outcomes of pyrocarbon spherical
implants for arthroplasty of the first CMC in patients with Eaton-Littler stage
II and III osteoarthritis. A single surgeon performed 24 arthroplasties (23
patients [20 women, three men] with a mean age of 56 years [range 46 to 75
years]) of the first CMC (nine right hands and 15 left hands) using pyrocarbon
spherical implants from May 2010 to April 2013. All patients failed conservative
management. At a mean (+/- SD) of 18.5+/-11.16 months postoperatively (range 4.3
to 38.9 months), the mean Kapandji score was 8.8 of 10 (range 7 to 10), the
average pre- and postoperative values on the visual pain scale were 8.96+/-0.64
of 10 (range 8 to 10) and 1.13+/-1.22 of 10 (range 0 to 4), respectively. All
patients were either very satisfied (score = 5) or satisfied (score = 4) with the
procedure, with a mean satisfaction score of 4.76+/-0.44 of 5.00 (range 4 to 5).
The mean postoperative Disabilities of the Arm, Shoulder and Hand (DASH) score
was 11.79+/-14.29 (range 0 to 49.17). The most recent radiographic evaluations
confirmed that all implants were stable with no erosion of nearby cancellous
bone. There were no implant subluxations, dislocations or revisions. Early
outcomes show promising results and support continued use of this implant for
arthroplasty. However, longer-term follow-up will be needed to confirm these
results.
PMID- 25114618
TI - Testing the effects of long-acting steroids in edema and ecchymosis after closed
rhinoplasty.
AB - BACKGROUND: Steroids have proven to be of some benefit in rhinoplasty edema and
ecchymosis when administered at a high and repeated dose. OBJECTIVE: To evaluate
the effects of single-dose, long-acting intramuscular steroids on postoperative
edema and ecchymosis after closed rhinoplasty with osteotomies compared with
placebo. METHODS: A randomized, double-blinded, placebo-controlled trial was
performed. Fifty-four patients were randomly assigned to two groups: 28 received
a single dose of long-acting dexamethasone (mean [+/- SD] dose 16+/-4 mg)
immediately before anesthetic induction; the remaining 26 received an
intramuscular injection of saline solution. The same surgeon performed all
surgeries, with patients under general anesthesia. Acetaminophen was the only
analgesic used to control postoperative pain. High-resolution digital photographs
were taken on postoperative days 1, 3, 7 and 14. Scoring was performed separately
for eyelid swelling and ecchymosis by an independent observer using a graded
scale (0 to 5) for edema and a scoring system (0 to 13) for ecchymosis. RESULTS:
No statistically significant differences in terms of age, sex or amount of
bleeding during surgery were found between the two groups. No statistically
significant difference was observed in the decrease of both ecchymosis and edema
between placebo and high-dose, long-acting dexamethasone. A statistically
significant difference in operation time was found, favouring the steroid group.
No severe complications were observed due to steroid use. DISCUSSION: Osteotomies
are basically a form of (controlled) trauma, with considerable disruption of the
abundant blood vessels in this facial region and, therefore, are associated with
with undesirable effects. A recent meta-analysis failed to show benefits of the
use of steroids after postoperative day 3. Only a trend toward reduction in edema
and ecchymosis with the use of long-acting steroids compared with placebo was
demonstrated in the present study. CONCLUSION: There was no benefit in
administering single-dose, long-acting steroids in patients undergoing closed
rhinoplasty with osteotomies.
PMID- 25114619
TI - The unfunded costs incurred by patients accessing plastic surgical care in
Northern Saskatchewan.
AB - The Canadian health care system was designed to ensure that all Canadian citizens
would receive equal access to health care. However, in rural areas of Canada,
patients are required to travel long distances and pay significant out-of-pocket
expenses to access health care. The present study attempted to quantify the added
out-of-pocket costs that rural Saskatchewan residents must pay to receive plastic
surgical specialist care compared with urban residents of Saskatoon. A cost
analysis was performed to generate a numerical value that would represent a
minimum cost for patients travelling from three different locations within the
province. The cost analysis performed in the present study approximated that the
unfunded costs for common plastic surgical procedures are, at a minimum, 30 times
greater for rural patients in La Ronge compared with their urban counterparts in
Saskatoon. The fundamental principle of the Canadian health care system is equal
access to necessary health care for all Canadians. Despite this, inequalities
persist. The present cost-analysis study demonstrated that the unfunded (out-of
pocket) expenses for rural Saskatchewan patients seeking plastic surgical
treatment is significantly higher than for their urban counterparts. These
unfunded costs represent a significant barrier to health care access in Canada
and serve to propagate inequalities in the nation's heath care system.
PMID- 25114620
TI - Meta-analysis of antibiotic prophylaxis in breast reduction surgery.
AB - BACKGROUND: Breast reduction surgery is a very common procedure; however, there
is still no consensus as to whether antibiotics should be used perioperatively.
OBJECTIVE: To review the world literature and perform a meta-analysis of studies
comparing wound infection rates with antibiotic use in breast reduction surgery.
METHODS: A literature search was performed using the MEDLINE, Cochrane Database
of Systematic Reviews, Cochrane Database of Clinical Trials, Embase and CINAHL
databases. Subject headings and relevant subheadings for "Breast", "Breast
Reduction", "Reduction Mammaplasty", "Mammaplasty" were combined with
"Antibiotics" and "Antibacterial Agents". The list of titles was assessed by the
study's authors and abstracts were reviewed. All relevant articles were then
independently reviewed by the two primary authors, and Jadad scoring was used to
assess the quality of the included articles. RESULTS: From the original search,
three randomized controlled trials were included in the meta-analysis of
preoperative antibiotics. The meta-analysis revealed a 75% reduction in wound
infections with preoperative antibiotics (OR 0.25 [95% CI 0.09 to 0.72]). Because
only one randomized controlled trial analyzed postoperative antibiotics, no meta
analysis could be performed. CONCLUSIONS: Preoperative antibiotics should
routinely be used before breast reduction surgery. The use of postoperative
antibiotics remains controversial. Additional randomized studies investigating
postoperative antibiotics are needed.
PMID- 25114621
TI - A review of hydrofluoric acid burn management.
AB - Hydrofluoric acid (HF) causes a unique chemical burn. Much of the current
treatment knowledge of HF burns is derived from case reports, small case series,
animal studies and anecdotal evidence. The management can be challenging because
clinical presentation and severity of these burns vary widely. Plastic surgeons
managing burn patients must have a basic understanding of the pathophysiology,
the range of severity in presentation and the current treatment options available
for HF burns. The present article reviews the current understanding of the
pathophysiology and systemic effects associated with severe HF burns.
Furthermore, it distinguishes between minor and life-threatening HF burns and
describes several of the basic techniques that are available to treat patients
with HF burns.
PMID- 25114622
TI - Inpatient silver sulphadiazine versus outpatient nanocrystalline silver models of
care for pediatric scald burns: A value analysis.
AB - BACKGROUND/OBJECTIVE: Scalds represent the most frequent pediatric burn injury.
Inpatient nonsurgical wound management of small or medium-size burns (<20% total
body surface area) represents a significant proportion of the cost of care, with
nanocrystalline silver (NCS) and silver sulphadiazine (SSD) among the most
commonly used dressings. Although several articles have described healing
outcomes using these dressings, there are few concurrent economic analyses. To
analyze overall health care value (outcomes/cost) in burns not requiring surgery,
the authors compared management of scald burns with NCS versus SSD from both a
quality perspective and using bottom-up microcosting to determine which dressing
option optimizes health care value. METHODS: A value analysis was performed.
Published studies investigating NCS and/or SSD in the treatment of pediatric
burns over the past 25 years were analyzed. Healing time, hospital duration and
frequency of dressings were chosen as quality metrics. A bottom-up microcosting
analysis was performed to estimate costs associated with the two dressing
options. RESULTS: Over the 25-year period, 356 studies investigated the use of
SSD in burns, while 55 studies evaluated the use of NCS. Mean age and burn size
were equivalent. Mean time to healing was 14.9 days for NCS and 17.2 days for
SSD. The mean duration of hospital stay was 14.9 days for SSD and 5.9 days for
NCS. Dressings were performed twice per week for NCS, and once or twice per day
for SSD. The mean total cost per patient to the health care system was estimated
to be $61,140 for SSD and $17,220 for NCS. CONCLUSION: Published outcomes of
healing time are equivalent or slightly better using NCS over SSD for pediatric
scalds. The financial model illustrated a potential significant cost saving with
NCS, primarily as a result of an outpatient model of care. Overall health care
value is optimized using NCS for pediatric scalds.
PMID- 25114625
TI - Oral exam.
PMID- 25114626
TI - The instruments of debt.
PMID- 25114624
TI - Is routine pathological evaluation of tissue from gynecomastia necessary? A 15
year retrospective pathological and literature review.
AB - OBJECTIVE: To reconsider the routine plastic surgical practice of requesting
histopathological evaluation of tissue from gynecomastia. METHOD: The present
study was a retrospective histopathological review (15-year period [1996 to
2012]) involving gynecomastia tissue samples received at the pathology laboratory
in the Saskatoon Health Region (Saskatchewan). The Laboratory Information System
(LIS) identified all specimens using the key search words "gynecomastia",
"gynaecomastia", "gynecomazia" and "gynaecomazia". A literature review to
identify all cases of incidentally discovered malignancies in gynecomastia tissue
specimens over a 15-year period (1996 to present) was undertaken. RESULTS: The 15
year LIS search detected a total of 452 patients that included two cases of
pseudogynecomastia (0.4%). Patients' age ranged from five to 92 years and 43% of
the cases were bilateral (28% left sided, 29% right sided). The weight of the
specimens received ranged from 0.2 g to 1147.2 g. All cases showed no significant
histopathological concerns. The number of tissue blocks sampled ranged from one
to 42, averaging four blocks/case (approximately $105/case), resulting in a cost
of approximately $3,200/year, with a 15-year expenditure of approximately
$48,000. The literature review identified a total of 15 incidental findings:
ductal carcinoma in situ (12 cases), atypical ductal hyperplasia (two cases) and
infiltrating ductal carcinoma (one case). CONCLUSIONS: In the context of evidence
based literature, and because no significant pathological findings were detected
in this particular cohort of 452 cases with 2178 slides, the authors believe it
is time to re-evaluate whether routine histopathological examination of tissue
from gynecomastia remains necessary. The current climate of health care budget
fiscal restraints warrants reassessment of the current policies and practices of
sending tissue samples of gynecomastia incurring negative productivity costs on
routine histopathological examination.
PMID- 25114623
TI - Breast reconstruction following prophylactic or therapeutic mastectomy for breast
cancer: Recommendations from an evidence-based provincial guideline.
AB - The side effects of mastectomy can be significant. Breast reconstruction may
alleviate some distress; however, there are currently no provincial
recommendations regarding the integration of reconstruction with breast cancer
therapy. The purpose of the present article is to provide evidence-based
strategies for the management of patients who are candidates for reconstruction.
A systematic review of meta-analyses, guidelines, clinical trials and comparative
studies published between 1980 and 2013 was conducted using the PubMed and EMBASE
databases. Reference lists of publications were manually searched for additional
literature. The National Guidelines Clearinghouse and SAGE directory, as well as
guideline developers' websites, were also searched. Recommendations were
developed based on the available evidence. Reconstruction consultation should be
made available for patients undergoing mastectomy. Tumour characteristics, cancer
therapy, patient comorbidities, body habitus and smoking history may affect
reconstruction outcomes. Although immediate reconstruction should be considered
whenever possible, delayed reconstruction is acceptable when immediate is not
available or appropriate. The integration of reconstruction and postmastectomy
radiotherapy should be addressed in a multidisciplinary setting. The decision as
to which type of procedure to perform (autologous or alloplastic with or without
acellular dermal matrices) should be left to the discretion of the surgeons and
the patient after providing counselling. Skin-sparing mastectomy is safe and
appropriate. Nipple-sparing is generally not recommended for patients with
malignancy, but could be considered for carefully selected patients. Immediate
reconstruction requires resources to coordinate operating room time between the
general and plastic surgeons, to provide supplies including acellular dermal
matrices, and to develop the infrastructure needed to facilitate
multidisciplinary discussions.
PMID- 25114627
TI - Development of positive antinuclear antibodies and rheumatoid factor in systemic
juvenile idiopathic arthritis points toward an autoimmune phenotype later in the
disease course.
AB - BACKGROUND: Systemic juvenile idiopathic arthritis (sJIA) is commonly considered
an autoinflammatory disease. However, sJIA patients may develop aggressive
arthritis without systemic inflammation later in the disease, resembling an
autoimmune phenotype similar to other subtypes of JIA. The objective of this
study was to determine whether antinuclear antibodies (ANA) and rheumatoid factor
(RF) will develop in patients with sJIA over the course of the disease. FINDINGS:
A single center sample of sJIA patients with follow-up of more than one year was
obtained. A retrospective chart survey was used to extract demographic and
clinical data as well as presence and titers of ANA and RF at diagnosis and
during follow-up. 32 patients were included in the study, with a median age of
4.2 years and median follow-up of 6.0 years. 8/32 patients had ANA titers >= 1:80
at diagnosis, with 22/32 patients showing rising ANA titers with titers >= 1:80
at last follow-up (p =0.001). 10/32 patients had a positive RF at least once
during follow-up, compared to 0/32 at diagnosis (p = 0.001). In 5/10 patients,
positive RF was documented at least twice, more than twelve weeks apart. Patients
treated with TNF antagonists were not significantly more likely to develop
positive ANA titers (p = 0.425) or positive RF (p = 0.703). CONCLUSIONS: Patients
with sJIA developed increased ANA titers and positive RF over the course of the
disease, independent of treatment with TNF antagonists. This might point towards
an autoimmune, rather than an autoinflammatory phenotype later in the course of
sJIA.
PMID- 25114628
TI - Regorafenib: an evidence-based review of its potential in patients with advanced
liver cancer.
AB - Hepatocellular carcinoma (HCC) is the second-most common cause of cancer-related
death in the world. In spite of HCC surveillance with repeated imaging, about 50%
of patients are diagnosed at an advanced stage and are not amenable to curative
treatment options. Sorafenib, a multikinase inhibitor, remains the standard of
care for advanced HCC. Over the last 5 years, several other medications have been
tested in Phase III trials. However, they have not shown any added benefit over
sorafenib. Regorafenib, another multikinase inhibitor, has demonstrated
inhibition of a broader range of kinases, along with higher inhibition potential
in preclinical models. After its safety and pharmacological properties was
studied in Phase I trials, a Phase II study evaluating the role of Regorafenib in
patients with advanced HCC who progressed on sorafenib therapy demonstrated
efficacy and a manageable safety profile. A Phase III trial is ongoing, and its
result will help us better evaluate the role of Regorafenib in patients with
advanced HCC.
PMID- 25114629
TI - Structural damage of chicken red blood cells exposed to platinum nanoparticles
and cisplatin.
AB - Side effects and resistance of cancer cells to cisplatin are major drawbacks to
its application, and recently, the possibility of replacing cisplatin with
nanocompounds has been considered. Most chemotherapeutic agents are administered
intravenously, and comparisons between the interactions of platinum nanoparticles
(NP-Pt) and cisplatin with blood compartments are important for future
applications. This study investigated structural damage, cell membrane
deformation and haemolysis of chicken embryo red blood cells (RBC) after
treatment with cisplatin and NP-Pt. Cisplatin (4 MUg/ml) and NP-Pt (2,6 MUg/ml),
when incubated with chicken embryo RBC, were detrimental to cell structure and
induced haemolysis. The level of haemolytic injury was increased after cisplatin
and NP-Pt treatments compared to the control group. Treatment with cisplatin
caused structural damage to cell membranes and the appearance of keratocytes,
while NP-Pt caused cell membrane deformations (discoid shape of cells was lost)
and the formation of knizocytes and echinocytes. This work demonstrated that NP
Pt have potential applications in anticancer therapy, but potential toxic side
effects must be explored in future preclinical research.
PMID- 25114630
TI - Synthesis of mixed-sequence oligonucleotides on mesoporous silicon: chemical
strategies and material stability.
AB - Rapid screening tests in medical diagnostic and environmental analysis are often
based on oligonucleotide biochips. In this paper, we studied the stability of
functionalized mesoporous silicon supports in the solid-phase synthesis of
oligonucleotides, exploiting several chemical procedures. A 19-mer mixed sequence
has been successfully synthesized on aminosilane-modified porous silicon photonic
structures. The process and the materials have been characterized by optical
reflectivity, atomic force microscopy and high-performance liquid chromatography.
PMID- 25114631
TI - Thermal conductivity of highly porous Si in the temperature range 4.2 to 20 K.
AB - We report on experimental results of the thermal conductivity k of highly porous
Si in the temperature range 4.2 to 20 K, obtained using the direct current (dc)
method combined with thermal finite element simulations. The reported results are
the first in the literature for this temperature range. It was found that porous
Si thermal conductivity at these temperatures shows a plateau-like temperature
dependence similar to that obtained in glasses, with a constant k value as low as
0.04 W/m.K. This behavior is attributed to the presence of a majority of non
propagating vibrational modes, resulting from the nanoscale fractal structure of
the material. By examining the fractal geometry of porous Si and its fractal
dimensionality, which was smaller than two for the specific porous Si material
used, we propose that a band of fractons (the localized vibrational excitations
of a fractal lattice) is responsible for the observed plateau. The above results
complement previous results by the authors in the temperature range 20 to 350 K.
In this temperature range, a monotonic increase of k with temperature is
observed, fitted with simplified classical models. The extremely low thermal
conductivity of porous Si, especially at cryogenic temperatures, makes this
material an excellent substrate for Si-integrated microcooling devices (micro
coldplate). PACS: 61.43.-j; 63.22.-m; 65.8.-g.
PMID- 25114632
TI - Efficiency enhancement of non-selenized Cu(In,Ga)Se2 solar cells employing
scalable low-cost antireflective coating.
AB - In this study, a non-selenized CuInGaSe2 (CIGS) solar device with textured zinc
oxide (ZnO) antireflection coatings was studied. The ZnO nanostructure was
fabricated by a low-temperature aqueous solution deposition method. With
controlling the morphology of the solution-grown tapered ZnO nanorod coatings,
the average reflectance of the CIGS solar device decreased from 8.6% to 2.1%, and
the energy conversion efficiency increased from 9.1% to 11.1%. The performance
improvement in the CuInGaSe2 thin-film solar cell was well explained due to the
gradual increase of the refractive index between air and the top electrode of
solar cell device by the insertion of the ZnO nanostructure. The results
demonstrate a potential application of the ZnO nanostructure array for efficient
solar device technology.
PMID- 25114634
TI - Growth of arrays of oriented epitaxial platinum nanoparticles with controlled
size and shape by natural colloidal lithography.
AB - We developed a method for production of arrays of platinum nanocrystals of
controlled size and shape using templates from ordered silica bead monolayers.
Silica beads with nominal sizes of 150 and 450 nm were self-assembled into
monolayers over strontium titanate single crystal substrates. The monolayers were
used as shadow masks for platinum metal deposition on the substrate using the
three-step evaporation technique. Produced arrays of epitaxial platinum islands
were transformed into nanocrystals by annealing in a quartz tube in nitrogen
flow. The shape of particles is determined by the substrate crystallography,
while the size of the particles and their spacing are controlled by the size of
the silica beads in the monolayer mask. As a proof of concept, arrays of platinum
nanocrystals of cubooctahedral shape were prepared on (100) strontium titanate
substrates. The nanocrystal arrays were characterized by atomic force microscopy,
scanning electron microscopy, and synchrotron X-ray diffraction techniques.
PMID- 25114633
TI - Nitric oxide-releasing porous silicon nanoparticles.
AB - In this study, the ability of porous silicon nanoparticles (PSi NPs) to entrap
and deliver nitric oxide (NO) as an effective antibacterial agent is tested
against different Gram-positive and Gram-negative bacteria. NO was entrapped
inside PSi NPs functionalized by means of the thermal hydrocarbonization (THC)
process. Subsequent reduction of nitrite in the presence of d-glucose led to the
production of large NO payloads without reducing the biocompatibility of the PSi
NPs with mammalian cells. The resulting PSi NPs demonstrated sustained release of
NO and showed remarkable antibacterial efficiency and anti-biofilm-forming
properties. These results will set the stage to develop antimicrobial
nanoparticle formulations for applications in chronic wound treatment.
PMID- 25114636
TI - Magnetic field dependence of singlet oxygen generation by nanoporous silicon.
AB - Energy transfer from photoexcited excitons localized in silicon nanoparticles to
adsorbed oxygen molecules excites them to the reactive singlet spin state. This
process has been studied experimentally as a function of nanoparticle size and
applied external magnetic field as a test of the accepted understanding of this
process in terms of the exchange coupling between the nano-Si exciton and the
adsorbed O2 molecules.
PMID- 25114635
TI - Preparation and nanoencapsulation of l-asparaginase II in chitosan
tripolyphosphate nanoparticles and in vitro release study.
AB - This paper describes the production, purification, and immobilization of l
asparaginase II (ASNase II) in chitosan nanoparticles (CSNPs). ASNase II is an
effective antineoplastic agent, used in the acute lymphoblastic leukemia
chemotherapy. Cloned ASNase II gene (ansB) in pAED4 plasmid was transformed into
Escherichia coli BL21pLysS (DE3) competent cells and expressed under optimal
conditions. The lyophilized enzyme was loaded into CSNPs by ionotropic gelation
method. In order to get optimal entrapment efficiency, CSNP preparation,
chitosan/tripolyphosphate (CS/TPP) ratio, and protein loading were investigated.
ASNase II loading into CSNPs was confirmed by Fourier transform infrared (FTIR)
spectroscopy, and morphological observation was carried out by transmission
electron microscopy. Three absolute CS/TPP ratios were studied. Entrapment
efficiency and loading capacity increased with increasing CS and TPP
concentration. The best ratio was applied for obtaining optimal ASNase II-loaded
CSNPs with the highest entrapment efficiency. Size, zeta potential, entrapment
efficiency, and loading capacity of the optimal ASNase II-CSNPs were 340 +/- 12
nm, 21.2 +/- 3 mV, 76.2% and 47.6%, respectively. The immobilized enzyme showed
an increased in vitro half-life in comparison with the free enzyme. The pH and
thermostability of the immobilized enzyme was comparable with the free enzyme.
This study leads to a better understanding of how to prepare CSNPs, how to
achieve high encapsulation efficiency for a high molecular weight protein, and
how to prolong the release of protein from CSNPs. A conceptual understanding of
biological responses to ASNase II-loaded CSNPs is needed for the development of
novel methods of drug delivery.
PMID- 25114637
TI - Bovine serum albumin nanoparticles as controlled release carrier for local drug
delivery to the inner ear.
AB - Nanoparticles have attracted increasing attention for local drug delivery to the
inner ear recently. Bovine serum albumin (BSA) nanoparticles were prepared by
desolvation method followed by glutaraldehyde fixation or heat denaturation. The
nanoparticles were spherical in shape with an average diameter of 492 nm. The
heat-denatured nanoparticles had good cytocompatibility. The nanoparticles could
adhere on and penetrate through the round window membrane of guinea pigs. The
nanoparticles were analyzed as drug carriers to investigate the loading capacity
and release behaviors. Rhodamine B was used as a model drug in this paper.
Rhodamine B-loaded nanoparticles showed a controlled release profile and could be
deposited on the osseous spiral lamina. We considered that the bovine serum
albumin nanoparticles may have potential applications in the field of local drug
delivery in the treatment of inner ear disorders.
PMID- 25114638
TI - Fabrication and sensing behavior of one-dimensional ZnO-Zn2GeO4 heterostructures.
AB - Well-crystalline one-dimensional ZnO-Zn2GeO4 (ZGO) heterostructures were
successfully synthesized using a high-temperature solid-state reaction between
the ZnO and Ge layers of ZnO-Ge core-shell nanostructures. The polycrystalline
ZGO crystallites had a thickness in the range of 17 to 26 nm. The high
temperature solid-state reaction induced grooves and crystal defects on the
surfaces of the ZGO crystallites. The sensors made from the ZnO-ZGO
heterostructures exhibited a marked photocurrent response to UV light at room
temperature and a gas sensing response to acetone gas at 325 degrees C. The
observed sensing properties are attributed to the rugged surface of the ZGO
heterointerfaces between ZnO and ZGO, surface crystal defects of ZGO, and cross
linked contact regions of ZnO-ZGO.
PMID- 25114639
TI - Controlled atom transfer radical polymerization of MMA onto the surface of high
density functionalized graphene oxide.
AB - We report on the grafting of poly(methyl methacrylate) (PMMA) onto the surface of
high-density functionalized graphene oxides (GO) through controlled radical
polymerization (CRP). To increase the density of surface grafting, GO was first
diazotized (DGO), followed by esterification with 2-bromoisobutyryl bromide,
which resulted in an atom transfer radical polymerization (ATRP) initiator
functionalized DGO-Br. The functionalized DGO-Br was characterized by X-ray
photoelectron spectroscopy (XPS), Raman, and XRD patterns. PMMA chains were then
grafted onto the DGO-Br surface through a 'grafting from' technique using ATRP.
Gel permeation chromatography (GPC) results revealed that polymerization of
methyl methacrylate (MMA) follows CRP. Thermal studies show that the resulting
graphene-PMMA nanocomposites have higher thermal stability and glass transition
temperatures (T g) than those of pristine PMMA.
PMID- 25114640
TI - Size evolution of ion beam synthesized Pb nanoparticles in Al.
AB - The size evolution of Pb nanoparticles (NPs) synthesized by ion implantation in
an epitaxial Al film has been experimentally investigated. The average radius R
of Pb NPs was determined as a function of implantation fluence f. The R(f) data
were analyzed using various growth models. Our observations suggest that the size
evolution of Pb NPs is controlled by the diffusion-limited growth kinetics (R
(2)?f). With increasing implantation current density, the diffusion coefficient
of Pb atoms in Al is evident to be enhanced. By a comparative analysis of the
R(f) data, values of the diffusion coefficient of Pb in Al were obtained.
PMID- 25114641
TI - Low-temperature growth of highly crystalline beta-Ga2O3 nanowires by solid-source
chemical vapor deposition.
AB - Growing Ga2O3 dielectric materials at a moderately low temperature is important
for the further development of high-mobility III-V semiconductor-based
nanoelectronics. Here, beta-Ga2O3 nanowires are successfully synthesized at a
relatively low temperature of 610 degrees C by solid-source chemical vapor
deposition employing GaAs powders as the source material, which is in a distinct
contrast to the typical synthesis temperature of above 1,000 degrees C as
reported by other methods. In this work, the prepared beta-Ga2O3 nanowires are
mainly composed of Ga and O elements with an atomic ratio of approximately 2:3.
Importantly, they are highly crystalline in the monoclinic structure with varied
growth orientations in low-index planes. The bandgap of the beta-Ga2O3 nanowires
is determined to be 251 nm (approximately 4.94 eV), in good accordance with the
literature. Also, electrical characterization reveals that the individual
nanowire has a resistivity of up to 8.5 * 10(7) Omega cm, when fabricated in the
configuration of parallel arrays, further indicating the promise of growing these
highly insulating Ga2O3 materials in this III-V nanowire-compatible growth
condition. PACS: 77.55.D; 61.46.Km; 78.40.Fy.
PMID- 25114643
TI - Tailoring the grooved texture of electrospun polystyrene nanofibers by
controlling the solvent system and relative humidity.
AB - In this study, we have successfully fabricated electrospun polystyrene (PS)
nanofibers having a diameter of 326 +/- 50 nm with a parallel grooved texture
using a mixed solvent of tetrahydrofuran (THF) and N,N-dimethylformamide (DMF).
We discovered that solvent system, solution concentration, and relative humidity
were the three key factors to the formation of grooved texture and the diameter
of nanofibers. We demonstrated that grooved nanofibers with desired properties
(e.g., different numbers of grooves, widths between two adjacent grooves, and
depths of grooves) could be electrospun under certain conditions. When THF/DMF
ratio was higher than 2:1, the formation mechanism of single grooved texture
should be attributed to the formation of voids on the jet surface at the early
stage of electrospinning and subsequent elongation and solidification of the
voids into a line surface structure. When THF/DMF ratio was 1:1, the formation
mechanism of grooved texture should be ascribed to the formation of wrinkled
surface on the jet surface at the early stage of electrospinning and subsequent
elongation into a grooved texture. Such findings can serve as guidelines for the
preparation of grooved nanofibers with desired secondary morphology.
PMID- 25114642
TI - Graphene as a transparent conducting and surface field layer in planar Si solar
cells.
AB - This work presents an experimental and finite difference time domain (FDTD)
simulation-based study on the application of graphene as a transparent conducting
layer on a planar and untextured crystalline p-n silicon solar cell. A high
quality monolayer graphene with 97% transparency and 350 Omega/? sheet resistance
grown by atmospheric pressure chemical vapor deposition method was transferred
onto planar Si cells. An increase in efficiency from 5.38% to 7.85% was observed
upon deposition of graphene onto Si cells, which further increases to 8.94% upon
SiO2 deposition onto the graphene/Si structure. A large increase in photon
conversion efficiency as a result of graphene deposition shows that the
electronic interaction and the presence of an electric field at the graphene/Si
interface together play an important role in this improvement and additionally
lead to a reduction in series resistance due to the conducting nature of
graphene.
PMID- 25114644
TI - Well-ordered polymer nano-fibers with self-cleaning property by disturbing
crystallization process.
AB - Bionic self-cleaning surfaces with well-ordered polymer nano-fibers are firstly
fabricated by disturbing crystallization during one-step coating-curing process.
Orderly thin (100 nm) and long (5-10 MUm) polymer nano-fibers with a certain
direction are fabricated by external macroscopic force (F blow) interference
introduced by H2 gas flow, leading to superior superhydrophobicity with a water
contact angle (WCA) of 170 degrees and a water sliding angle (WSA) of 0-1
degrees . In contrast, nano-wires and nano-bridges (1-8 MUm in length/10-80 nm in
width) are generated by "spinning/stretching" under internal microscopic force (F
T) interference due to significant temperature difference in the non-uniform
cooling medium. The findings provide a novel theoretical basis for controllable
polymer "bionic lotus" surface and will further promote practical application in
many engineering fields such as drag-reduction and anti-icing.
PMID- 25114645
TI - Nylon 6 electrospun nanofibers mat as effective sorbent for the removal of
estrogens: kinetic and thermodynamic studies.
AB - Nylon 6 electrospun nanofibers mat was prepared via electrospinning for the
removal of three estrogens, namely, diethylstilbestrol (DES), dienestrol (DS),
and hexestrol (HEX) from aqueous solution. Static adsorption as well as the
dynamic adsorption was evaluated by means of batch and dynamic disk flow mode,
respectively. The kinetic study indicated that the adsorption of the target
compounds could be well fitted by the pseudo-second-order equation, suggesting
the intra-particle/membrane diffusion process as the rate-limiting step of the
adsorption process. The adsorption equilibrium data were all fitted well to the
Freundlich isotherm models, with a maximum adsorption capacity values in the
range of 97.71 to 208.95 mg/g, which can be compared to or moderately higher than
other sorbents published in the literatures. The dynamic disk mode studies
indicated that the mean removal yields of three model estrogens were over 95%
with a notable smaller amount of adsorbent (4 mg). Thermodynamic study revealed
that the adsorption process was exothermic and spontaneous in nature. Desorption
results showed that the adsorption capacity can remain up to 80% after seven
times usage. It was suggested that Nylon 6 electrospun nanofibers mat has great
potential as a novel effective sorbent material for estrogens removal.
PMID- 25114646
TI - Redistribution of elements of metals in plant tissues under treatment by non
ionic colloidal solution of biogenic metal nanoparticles.
AB - The content of metal elements in plant tissues of 10-day wheat seedlings after
seed pre-treatment and foliar treatment with non-ionic colloidal solution of
metal nanoparticles (Fe, Mn, Cu, Zn) was determined by an atomic absorption
spectrometer. It was shown that metal nanoparticles due to their physical
properties (nanoscale and uncharged state) were capable of penetrating rapidly
into plant cells and optimizing plant metabolic processes at the early stages of
growth and development.
PMID- 25114647
TI - The obtaining of high-density specimens and analysis of mechanical strength
characteristics of a composite based on ZrO2-WC nanopowders.
AB - The structures, processes of shrinkage, and phase composition of the compact
system ZrO2-WC, obtained by hot pressing with the transmission of high current,
are considered in the article. We found that as a result of compaction, the ZrO2
WC-ceramics have uniform density distribution, with the following optimal mode
consolidation values T = 1,350 degrees C, P = 30 MPa and t = 2 min. These
conditions allow us to achieve the best combination of ceramic properties by
criteria density and strength.
PMID- 25114648
TI - Scandium effect on the luminescence of Er-Sc silicates prepared from multi
nanolayer films.
AB - Polycrystalline Er-Sc silicates (Er x Sc2-x Si2O7 and Er x Sc2-x SiO5) were
fabricated using multilayer nanostructured films of Er2O3/SiO2/Sc2O3 deposited on
SiO2/Si substrates by RF sputtering and thermal annealing at high temperature.
The films were characterized by synchrotron radiation grazing incidence X-ray
diffraction, cross-sectional transmission electron microscopy, energy-dispersive
X-ray spectroscopy, and micro-photoluminescence measurements. The Er-Sc silicate
phase Er x Sc2-x Si2O7 is the dominant film, and Er and Sc are homogeneously
distributed after thermal treatment because of the excess of oxygen from SiO2
interlayers. The Er concentration of 6.7 * 10(21) atoms/cm(3) was achieved due to
the presence of Sc that dilutes the Er concentration and generates concentration
quenching. During silicate formation, the erbium diffusion coefficient in the
silicate phase is estimated to be 1 * 10(-15) cm(2)/s at 1,250 degrees C. The
dominant Er x Sc2 - x Si2O7 layer shows a room-temperature photoluminescence peak
at 1,537 nm with the full width at half maximum (FWHM) of 1.6 nm. The peak
emission shift compared to that of the Y-Er silicate (where Y and Er have almost
the same ionic radii) and the narrow FWHM are due to the small ionic radii of
Sc(3+) which enhance the crystal field strength affecting the optical properties
of Er(3+) ions located at the well-defined lattice sites of the Sc silicate. The
Er-Sc silicate with narrow FWHM opens a promising way to prepare photonic crystal
light-emitting devices.
PMID- 25114649
TI - Beneficial defects: exploiting the intrinsic polishing-induced wafer roughness
for the catalyst-free growth of Ge in-plane nanowires.
AB - We outline a metal-free fabrication route of in-plane Ge nanowires on Ge(001)
substrates. By positively exploiting the polishing-induced defects of standard
quality commercial Ge(001) wafers, micrometer-length wires are grown by physical
vapor deposition in ultra-high-vacuum environment. The shape of the wires can be
tailored by the epitaxial strain induced by subsequent Si deposition, determining
a progressive transformation of the wires in SiGe faceted quantum dots. This
shape transition is described by finite element simulations of continuous
elasticity and gives hints on the equilibrium shape of nanocrystals in the
presence of tensile epitaxial strain. PACS: 81.07.Gf; 68.35.bg; 68.35.bj;
62.23.Eg.
PMID- 25114650
TI - Complex microstructures of ABC triblock copolymer thin films directed by polymer
brushes based on self-consistent field theory.
AB - The morphology and the phase diagram of ABC triblock copolymer thin film directed
by polymer brushes are investigated by the self-consistent field theory in three
dimensions. The polymer brushes coated on the substrate can be used as a good
soft template to tailor the morphology of the block copolymer thin films compared
with those on the hard substrates. The polymer brush is identical with the middle
block B. By continuously changing the composition of the block copolymer, the
phase diagrams are constructed for three cases with the fixed film thickness and
the brush density: identical interaction parameters, frustrated and non
frustrated cases. Some ordered complex morphologies are observed: parallel
lamellar phase with hexagonally packed pores at surfaces (LAM3 (ll) -HFs),
perpendicular lamellar phase with cylinders at the interface (LAM(?)-CI), and
perpendicular hexagonally packed cylinders phase with rings at the interface (C2
(?)-RI). A desired direction (perpendicular or parallel to the coated surfaces)
of lamellar phases or cylindrical phases can be obtained by varying the
composition and the interactions between different blocks. The phase diagram of
ABC triblock copolymer thin film wetted between the polymer brush-coated surfaces
is very useful in designing the directed pattern of ABC triblock copolymer thin
film.
PMID- 25114651
TI - Low-cost carbon-silicon nanocomposite anodes for lithium ion batteries.
AB - The specific energy of the existing lithium ion battery cells is limited because
intercalation electrodes made of activated carbon (AC) materials have limited
lithium ion storage capacities. Carbon nanotubes, graphene, and carbon nanofibers
are the most sought alternatives to replace AC materials but their synthesis cost
makes them highly prohibitive. Silicon has recently emerged as a strong candidate
to replace existing graphite anodes due to its inherently large specific capacity
and low working potential. However, pure silicon electrodes have shown poor
mechanical integrity due to the dramatic expansion of the material during battery
operation. This results in high irreversible capacity and short cycle life. We
report on the synthesis and use of carbon and hybrid carbon-silicon
nanostructures made by a simplified thermo-mechanical milling process to produce
low-cost high-energy lithium ion battery anodes. Our work is based on an
abundant, cost-effective, and easy-to-launch source of carbon soot having
amorphous nature in combination with scrap silicon with crystalline nature. The
carbon soot is transformed in situ into graphene and graphitic carbon during
mechanical milling leading to superior elastic properties. Micro-Raman mapping
shows a well-dispersed microstructure for both carbon and silicon. The fabricated
composites are used for battery anodes, and the results are compared with
commercial anodes from MTI Corporation. The anodes are integrated in batteries
and tested; the results are compared to those seen in commercial batteries. For
quick laboratory assessment, all electrochemical cells were fabricated under
available environment conditions and they were tested at room temperature.
Initial electrochemical analysis results on specific capacity, efficiency, and
cyclability in comparison to currently available AC counterpart are promising to
advance cost-effective commercial lithium ion battery technology. The
electrochemical performance observed for carbon soot material is very interesting
given the fact that its production cost is away cheaper than activated carbon.
The cost of activated carbon is about $15/kg whereas the cost to manufacture
carbon soot as a by-product from large-scale milling of abundant graphite is
about $1/kg. Additionally, here, we propose a method that is environmentally
friendly with strong potential for industrialization.
PMID- 25114652
TI - Large-diameter titanium dioxide nanotube arrays as a scattering layer for high
efficiency dye-sensitized solar cell.
AB - Large-sized titanium dioxide (TiO2) nanotube arrays with an outer diameter of
approximately 500 nm have been successfully synthesized by potentiostatic
anodization at 180 V in a used electrolyte with the addition of 1.5 M lactic
acid. It is found that the synthesized large-diameter TiO2 nanotube array shows a
superior light scattering ability, which can be used as a light scattering layer
to significantly enhance the efficiency of TiO2 nanoparticle-based dye-sensitized
solar cells from 5.18% to 6.15%. The remarkable light scattering ability makes
the large-diameter TiO2 nanotube array a promising candidate for light management
in dye-sensitized solar cells (DSSCs).
PMID- 25114653
TI - Validation of a Janus role of methotrexate-based PEGylated chitosan nanoparticles
in vitro.
AB - Recently, methotrexate (MTX) has been used to target to folate (FA) receptor
overexpressing cancer cells for targeted drug delivery. However, the systematic
evaluation of MTX as a Janus-like agent has not been reported before. Here, we
explored the validity of using MTX playing an early-phase cancer-specific
targeting ligand cooperated with a late-phase therapeutic anticancer agent based
on the PEGylated chitosan (CS) nanoparticles (NPs) as drug carriers. Some
advantages of these nanoscaled drug delivery systems are as follows: (1) the NPs
can ensure minimal premature release of MTX at off-target site to reduce the side
effects to normal tissue; (2) MTX can function as a targeting ligand at target
site prior to cellular uptake; and (3) once internalized by the target cell, the
NPs can function as a prodrug formulation, releasing biologically active MTX
inside the cells. The (MTX + PEG)-CS-NPs presented a sustained/proteases-mediated
drug release. More importantly, compared with the PEG-CS-NPs and (FA + PEG)-CS
NPs, the (MTX + PEG)-CS-NPs showed a greater cellular uptake. Furthermore, the
(MTX + PEG)-CS-NPs demonstrated a superior cytotoxicity compare to the free MTX.
Our findings therefore validated that the MTX-loaded PEGylated CS-NPs can
simultaneously target and treat FA receptor-overexpressing cancer cells.
PMID- 25114654
TI - Internal resistor of multi-functional tunnel barrier for selectivity and
switching uniformity in resistive random access memory.
AB - In this research, we analyzed the multi-functional role of a tunnel barrier that
can be integrated in devices. This tunnel barrier, acting as an internal
resistor, changes its resistance with applied bias. Therefore, the current flow
in the devices can be controlled by a tunneling mechanism that modifies the
tunnel barrier thickness for non-linearity and switching uniformity of devices.
When a device is in a low-resistance state, the tunnel barrier controls the
current behavior of the device because most of the bias is applied to the tunnel
barrier owing to its higher resistance. Furthermore, the tunnel barrier induces
uniform filament formation during set operation with the tunnel barrier
controlling the current flow.
PMID- 25114655
TI - Green synthesis of protein capped silver nanoparticles from phytopathogenic
fungus Macrophomina phaseolina (Tassi) Goid with antimicrobial properties against
multidrug-resistant bacteria.
AB - In recent years, green synthesis of nanoparticles, i.e., synthesizing
nanoparticles using biological sources like bacteria, algae, fungus, or plant
extracts have attracted much attention due to its environment-friendly and
economic aspects. The present study demonstrates an eco-friendly and low-cost
method of biosynthesis of silver nanoparticles using cell-free filtrate of
phytopathogenic fungus Macrophomina phaseolina. UV-visible spectrum showed a peak
at 450 nm corresponding to the plasmon absorbance of silver nanoparticles.
Scanning electron microscopy (SEM), atomic force microscopy (AFM), and
transmission electron microscopy (TEM) revealed the presence of spherical silver
nanoparticles of the size range 5 to 40 nm, most of these being 16 to 20 nm in
diameter. X-ray diffraction (XRD) spectrum of the nanoparticles exhibited 2theta
values corresponding to silver nanoparticles. These nanoparticles were found to
be naturally protein coated. SDS-PAGE analysis showed the presence of an 85-kDa
protein band responsible for capping and stabilization of the silver
nanoparticles. Antimicrobial activities of the silver nanoparticles against human
as well as plant pathogenic multidrug-resistant bacteria were assayed. The
particles showed inhibitory effect on the growth kinetics of human and plant
bacteria. Furthermore, the genotoxic potential of the silver nanoparticles with
increasing concentrations was evaluated by DNA fragmentation studies using
plasmid DNA.
PMID- 25114656
TI - Van der Waals epitaxy and characterization of hexagonal boron nitride nanosheets
on graphene.
AB - Graphene is highly sensitive to environmental influences, and thus, it is
worthwhile to deposit protective layers on graphene without impairing its
excellent properties. Hexagonal boron nitride (h-BN), a well-known dielectric
material, may afford the necessary protection. In this research, we demonstrated
the van der Waals epitaxy of h-BN nanosheets on mechanically exfoliated graphene
by chemical vapor deposition, using borazine as the precursor to h-BN. The h-BN
nanosheets had a triangular morphology on a narrow graphene belt but a polygonal
morphology on a larger graphene film. The h-BN nanosheets on graphene were highly
crystalline, except for various in-plane lattice orientations. Interestingly, the
h-BN nanosheets preferred to grow on graphene than on SiO2/Si under the chosen
experimental conditions, and this selective growth spoke of potential promise for
application to the preparation of graphene/h-BN superlattice structures
fabricated on SiO2/Si.
PMID- 25114657
TI - Facile synthesis and electrochemical performances of hollow graphene spheres as
anode material for lithium-ion batteries.
AB - The hollow graphene oxide spheres have been successfully fabricated from graphene
oxide nanosheets utilizing a water-in-oil emulsion technique, which were prepared
from natural flake graphite by oxidation and ultrasonic treatment. The hollow
graphene oxide spheres were reduced to hollow graphene spheres at 500 degrees C
for 3 h under an atmosphere of Ar(95%)/H2(5%). The first reversible specific
capacity of the hollow graphene spheres was as high as 903 mAh g(-1) at a current
density of 50 mAh g(-1). Even at a high current density of 500 mAh g(-1), the
reversible specific capacity remained at 502 mAh g(-1). After 60 cycles, the
reversible capacity was still kept at 652 mAh g(-1) at the current density of 50
mAh g(-1). These results indicate that the prepared hollow graphene spheres
possess excellent electrochemical performances for lithium storage. The high rate
performance of hollow graphene spheres thanks to the hollow structure, thin and
porous shells consisting of graphene sheets. PACS: 81.05.ue; 61.48.Gh; 72.80.Vp.
PMID- 25114658
TI - Current-voltage characteristics of nanoplatelet-based conductive nanocomposites.
AB - In this study, a numerical modeling approach was used to investigate the current
voltage behavior of conductive nanoplatelet-based nanocomposites. A three
dimensional continuum Monte Carlo model was employed to randomly disperse the
nanoplatelets in a cubic representative volume element. A nonlinear finite
element-based model was developed to evaluate the electrical behavior of the
nanocomposite for different levels of the applied electric field. Also, the
effect of filler loading on nonlinear conductivity behavior of nanocomposites was
investigated. The validity of the developed model was verified through
qualitative comparison of the simulation results with results obtained from
experimental works.
PMID- 25114659
TI - Conductance modulation of charged lipid bilayer using electrolyte-gated graphene
field effect transistor.
AB - Graphene is an attention-grabbing material in electronics, physics, chemistry,
and even biology because of its unique properties such as high surface-area-to
volume ratio. Also, the ability of graphene-based materials to continuously tune
charge carriers from holes to electrons makes them promising for biological
applications, especially in lipid bilayer-based sensors. Furthermore, changes in
charged lipid membrane properties can be electrically detected by a graphene
based electrolyte-gated graphene field effect transistor (GFET). In this paper, a
monolayer graphene-based GFET with a focus on the conductance variation caused by
membrane electric charges and thickness is studied. Monolayer graphene
conductance as an electrical detection platform is suggested for neutral,
negative, and positive electric-charged membrane. The electric charge and
thickness of the lipid bilayer (Q LP and L LP) as a function of carrier density
are proposed, and the control parameters are defined. Finally, the proposed
analytical model is compared with experimental data which indicates good overall
agreement.
PMID- 25114660
TI - Controlled nanodot fabrication by rippling polycarbonate surface using an AFM
diamond tip.
AB - The single scratching test of polymer polycarbonate (PC) sample surface using an
atomic force microscope (AFM) diamond tip for fabricating ripple patterns has
been studied with the focus on the evaluation of the effect of the tip scratching
angle on the pattern formation. The experimental results indicated that the
different oriented ripples can be easily machined by controlling the scratching
angles of the AFM. And, the effects of the normal load and the feed on the
ripples formation and their periods were also studied. Based on the ripple
pattern formation, we firstly proposed a two-step scratching method to fabricate
controllable and oriented complex three-dimensional (3D) nanodot arrays. These
typical ripple formations can be described via a stick-slip and crack formation
process.
PMID- 25114661
TI - Electrical behavior and positive temperature coefficient effect of
graphene/polyvinylidene fluoride composites containing silver nanowires.
AB - Polyvinylidene fluoride (PVDF) composites filled with in situ thermally reduced
graphene oxide (TRG) and silver nanowire (AgNW) were prepared using solution
mixing followed by coagulation and thermal hot pressing. Binary TRG/PVDF
nanocomposites exhibited small percolation threshold of 0.12 vol % and low
electrical conductivity of approximately 10(-7) S/cm. Hybridization of TRGs with
AgNWs led to a significant improvement in electrical conductivity due to their
synergistic effect in conductivity. The bulk conductivity of hybrids was higher
than a combined total conductivity of TRG/PVDF and AgNW/PVDF composites at the
same filler loading. Furthermore, the resistivity of hybrid composites increased
with increasing temperature, giving rise to a positive temperature coefficient
(PTC) effect at the melting temperature of PVDF. The 0.04 vol % TRG/1 vol %
AgNW/PVDF hybrid exhibited pronounced PTC behavior, rendering this composite an
attractive material for making current limiting devices and temperature sensors.
PMID- 25114663
TI - Integration of care systems in Portugal: anatomy of recent reforms.
AB - BACKGROUND: Integrated care is increasingly present in the agenda of policy
makers, health professionals and researchers as a way to improve care services in
relation to access, quality, user satisfaction and efficiency. These are
overarching objectives of most sectoral reforms. However, health care and social
care services and systems are more and more dependent on the performance of each
other, imposing the logic of network. Demographic, epidemiologic and cultural
changes result in pressure to increase efficiency and efficacy of services and
organisations in both sectors and that is why integrated care has become so
relevant in the last years. METHODS: We first used concept maps to organise and
systematise information that we had gathered through deep literature review in
order to set a framework where to base the subsequent work. Then, we interviewed
informants at several levels of the health and social care systems and we built a
list of major recent reforms addressing integrated care in Portugal. In a third
step, we conducted two independent focus groups where those reforms were
discussed and evaluated within the context of the concepts and frameworks
identified from the literature. Results were confronted and reconciled, giving
place to a list of requisites and guidelines that oriented further search for
documentation on those reforms. RESULTS: Several important health reforms are in
course in primary and hospital care in Portugal, while a so-called third level of
care has been introduced with the launch of the National Network of Long-Term
Integrated Care (RNCCI - Rede Nacional de Cuidados Continuados Integrados). The
social care sector has itself been a subject of alternative models springing from
opposite political orientations. All these changes are having repercussions on
the way the systems work with each other as they are leading to ongoing and ill
evaluated reformulations on the way they are governed, financed, structured and
operated. CONCLUSIONS: Care integration is not absent from policy-making and
implementation endeavour in Portugal. However, recurrent issues seem to be
consistently hampering the efforts regarding the integration of care in the
country. It is urgent to assess current situation as experienced by those closely
involved and directly affected.
PMID- 25114662
TI - Validation of a blood protein signature for non-small cell lung cancer.
AB - BACKGROUND: CT screening for lung cancer is effective in reducing mortality, but
there are areas of concern, including a positive predictive value of 4% and
development of interval cancers. A blood test that could manage these limitations
would be useful, but development of such tests has been impaired by variations in
blood collection that may lead to poor reproducibility across populations.
RESULTS: Blood-based proteomic profiles were generated with SOMAscan technology,
which measured 1033 proteins. First, preanalytic variability was evaluated with
Sample Mapping Vectors (SMV), which are panels of proteins that detect
confounders in protein levels related to sample collection. A subset of well
collected serum samples not influenced by preanalytic variability was selected
for discovery of lung cancer biomarkers. The impact of sample collection
variation on these candidate markers was tested in the subset of samples with
higher SMV scores so that the most robust markers could be used to create disease
classifiers. The discovery sample set (n = 363) was from a multi-center study of
94 non-small cell lung cancer (NSCLC) cases and 269 long-term smokers and benign
pulmonary nodule controls. The analysis resulted in a 7-marker panel with an AUC
of 0.85 for all cases (68% adenocarcinoma, 32% squamous) and an AUC of 0.93 for
squamous cell carcinoma in particular. This panel was validated by making blinded
predictions in two independent cohorts (n = 138 in the first validation and n =
135 in the second). The model was recalibrated for a panel format prior to
unblinding the second cohort. The AUCs overall were 0.81 and 0.77, and for
squamous cell tumors alone were 0.89 and 0.87. The estimated negative predictive
value for a 15% disease prevalence was 93% overall and 99% for squamous lung
tumors. The proteins in the classifier function in destruction of the
extracellular matrix, metabolic homeostasis and inflammation. CONCLUSIONS:
Selecting biomarkers resistant to sample processing variation led to robust lung
cancer biomarkers that performed consistently in independent validations. They
form a sensitive signature for detection of lung cancer, especially squamous cell
histology. This non-invasive test could be used to improve the positive
predictive value of CT screening, with the potential to avoid invasive evaluation
of nonmalignant pulmonary nodules.
PMID- 25114664
TI - Do telemonitoring projects of heart failure fit the Chronic Care Model?
AB - This study describes the characteristics of extramural and transmural
telemonitoring projects on chronic heart failure in Belgium. It describes to what
extent these telemonitoring projects coincide with the Chronic Care Model of
Wagner. BACKGROUND: The Chronic Care Model describes essential components for
high-quality health care. Telemonitoring can be used to optimise home care for
chronic heart failure. It provides a potential prospective to change the current
care organisation. METHODS: This qualitative study describes seven non-invasive
home-care telemonitoring projects in patients with heart failure in Belgium. A
qualitative design, including interviews and literature review, was used to
describe the correspondence of these home-care telemonitoring projects with the
dimensions of the Chronic Care Model. RESULTS: The projects were situated in
primary and secondary health care. Their primary goal was to reduce the number of
readmissions for chronic heart failure. None of these projects succeeded in a
final implementation of telemonitoring in home care after the pilot phase. Not
all the projects were initiated to accomplish all of the dimensions of the
Chronic Care Model. A central role for the patient was sparse. CONCLUSION:
Limited financial resources hampered continuation after the pilot phase.
Cooperation and coordination in telemonitoring appears to be major barriers but
are, within primary care as well as between the lines of care, important links in
follow-up. This discrepancy can be prohibitive for deployment of good chronic
care. Chronic Care Model is recommended as basis for future.
PMID- 25114665
TI - Identification of mechanisms enabling integrated care for patients with chronic
diseases: a literature review.
AB - INTRODUCTION: Notwithstanding care for chronically ill patients requires a shift
towards care that is well coordinated and focused on prevention and self-care,
the concept of integrated care lacks specificity and clarity. This article
presents a literature review to identify mechanisms for achieving integrated care
objectives. THEORY AND METHODS: Existing models often present a large variety of
dimensions, archetypes and categories of integration without specifying them.
Models and programmes describing integrated care for chronic diseases were
reviewed. Data were extracted related to objectives and clusters of mechanisms of
integration. RESULTS: Thirty-four studies presented four objectives: functional,
organisational, professional and service integration. We categorised approaches
and interventions to achieve these objectives by strategy and clusters of
'mechanisms of integration': degree, patient centredness and normative aspects.
CONCLUSIONS AND DISCUSSION: The clarification of mechanisms to achieve objectives
of integrated care as presented may be used as starting point for the development
and refinement of integrated care programmes, including methodological grounding
of their evaluation. Given that most studies reviewed lack both empirical data
and descriptions of the methods used, future research needs to close these gaps.
Validation of the findings by a large panel of experts is suggested as
recommendation to work towards a grounded framework.
PMID- 25114666
TI - A neuropsychiatric complication of oligomenorrhea according to iranian
traditional medicine.
AB - Oligomenorrhea, a prevalent disease with serious complications, has been declared
in the Avicenna traditional medicine in detail. Avicenna in his famous book,
Cannon of Medicine, presents a syndrome termed 'uterine strangulation', as a
complication of menstrual bleeding cessation and lack of sexual satisfaction. We
have explained this syndrome from both traditional and conventional medicine
viewpoints to propose a new hypothesis for diagnosis and treatment of women with
oligomenorrhea and systemic signs/symptoms admitting to clinics for further
evaluation. This hypothesis definitely needs to be further assessed and confirmed
by strong clinical trials.
PMID- 25114667
TI - Evaluating the effects of Escanbil (Calligonum) extract on the expression level
of Catsper gene variants and sperm motility in aging male mice.
AB - BACKGROUND: Catsper proteins are responsible for entering Ca(2+) to the cell and
play an important role in sperm motility and male fertility. Antioxidants are
vital for sperm motility too. Escanbil (Calligonum) extract possess some of the
important antioxidant like Catechin and Quercetin. OBJECTIVE: Here we
investigated the effects of Escanbil (Calligonum) extract on the sperm parameters
and the expressing of Catsper gene in aging male mice. MATERIALS AND METHODS: In
this animal study, firstly, dose response was performed by using these three
doses of Escanbil (Calligonum) (10, 30 and 50 mg/kg). 5 mice in each group were
considered and Intra Peritoneal injection was done for 5 weeks. the sperm
parameters analyzed and dUTP nick end labeling (TUNEL )staining was done. 30
mg/kg dose was considered as optimum dose. Secondly: fifteen aging male mice (11
13 months) were divided into three groups: control, sham and experiment. The
experiments were injected Intra peritonealy with Escanbil (Calligonum) extract
(30mg/kg) weekly for up to 5 weeks. The sham group was injected Intra Peritoneal
(DMSO). Sperm parameters were analyzed. Expression of Catsper genes was analyzed
by Real time PCR. RESULTS: Our results showed that after Escanbil (Calligonum)
treatment (30 mg/kg), the sperm parameters were improved in experimental group
(p<0.05). Our data showed that there was a statistical significance difference
between the expressions of Catsper 2, 4 in aging experiment group comparison with
aging control group (p<0.05). CONCLUSION: We investigated that the Escanbil
(Calligonum) extract (30 mg/kg) can improve sperm parameters and change the
expression of Catsper genes in aging male mice. This herbal extract can be used
as an antioxidant component for clinical usages.
PMID- 25114668
TI - Recurrent IVF failure and hereditary thrombophilia.
AB - BACKGROUND: The largest percentage of failed invitro fertilization (IVF (cycles,
are due to lack of implantation. As hereditary thrombophilia can cause in
placentation failure, it may have a role in recurrent IVF failure. OBJECTIVE: Aim
of this case-control study was to determine whether hereditary thrombophilia is
more prevalent in women with recurrent IVF failures. MATERIALS AND METHODS: Case
group comprised 96 infertile women, with a history of recurrent IVF failure.
Control group was comprised of 95 healthy women with proven fertility who had
conceived spontaneously. All participants were assessed for the presence of
inherited thrombophilias including: factor V Leiden, methilen tetrahydrofolate
reductase (MTHFR) mutation, prothrombin mutation, homocystein level, protein S
and C deficiency, antithrombin III (AT-III) deficiency and plasminogen activator
inhibitor-1 (PAI-1) mutation. Presence of thrombophilia was compared between
groups. RESULTS: Having at least one thrombophilia known as a risk factor for
recurrent IVF failure (95% CI=1.74-5.70, OR=3.15, p=0.00). Mutation of factor V
Leiden (95% CI=1.26-10.27, OR=3.06, P=0.01) and homozygote form of MTHFR mutation
(95% CI=1.55-97.86, OR=12.33, p=0.05) were also risk factors for recurrent IVF
failure. However, we could not find significant difference in other inherited
thrombophilia's. CONCLUSION: Inherited thrombophilia is more prevalent in women
with recurrent IVF failure compared with healthy women. Having at least one
thrombophilia, mutation of factor V Leiden and homozygote form of MTHFR mutation
were risk factors for recurrent IVF failure.
PMID- 25114670
TI - Subclinical hypothyroidism and insulin resistance in polycystic ovary syndrome:
is there a relationship?
AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common hyperandrogenic
disorder among women and is often defined as hyperandrogenic syndrome. These
patients are at risk for oligo/amenorrhea, chronic anovulation, infertility,
obesity, spontaneous abortion, insulin resistance, hyperinsulinemia and metabolic
syndrome. Thyroid disorders especially hypothyroidism is more common in these
people. In PCOS patients, subclinical hypothyroidism may aggravate insulin
resistance. OBJECTIVE: The goal was to find any relationship between subclinical
hypothyroidism and insulin resistance in PCOS patients. MATERIALS AND METHODS: In
this prospective cross sectional study we included all PCOS patients coming to
infertility clinic of Taleghani Hospital in 2010-2012 who had the criteria of
Rotterdam for PCOS. Then the clinical examination was done for them and height,
weight, body mass index and lab data were measured including thyroid hormone and
biochemical profile. The data were analyzed by SPSS software version 20. RESULTS:
Among 75 PCOS patients, 19 (25.5%) had subclinical hypothyroidism and 56 patients
(74.4%) were euthyroid. The prevalence of insulin resistance was 22.7% and 77.3%
of patients had no insulin resistance were normal. CONCLUSION: We could find no
relationship between insulin resistance and subclinical hypothyroidism in PCOS
patients.
PMID- 25114669
TI - Emotional experiences in surrogate mothers: A qualitative study.
AB - BACKGROUND: Surrogacy is one of the new techniques of assisted reproduction
technology in which a woman carries and bears a child for another woman. In Iran,
many Shia clerics and jurists considered it permissible so there is no religious
prohibition for it. In addition to the risk of physical complications for
complete surrogate mothers, the possibility of psychological complications
resulted from emotional attachment to a living creature in the surrogate mother
as another injury requires counseling and assessment prior to acceptance by
infertile couples and complete surrogate mothers. OBJECTIVE: The purpose of this
study was to assess the emotional experiences of surrogate mothers. MATERIALS AND
METHODS: This was a qualitative, phenomenological study. We selected eight
complete surrogate mothers in Isfahan. We used convenient sampling method and in
depth interview to collect the information. The data analysis was fulfilled via
Colaizzi's seven-stage method. Reliability and validity study of the roots in the
four-axis was done. RESULTS: The findings of these interviews were classified
into two main themes and four sub themes: acquired experiences in pregnancy
(feelings toward pregnancy, relationship with family, relatives and commissioning
couple) and consequences of surrogacy (complications of pregnancy, religious and
financial problems of surrogacy). CONCLUSION: Surrogacy pregnancy should be
considered as high-risk emotional experience because many of surrogate mothers
may face negative experiences. Therefore, it is recommended that surrogates
should receive professional counseling prior to, during and following pregnancy.
PMID- 25114671
TI - Diagnostic value of gastric shake test for hyaline membrane disease in preterm
infant.
AB - BACKGROUND: Hyaline membrane disease (HMD) has remained a common neonatal problem
and is a cause of morbidity in infants. The shake test can be used to assess
whether surfactant is present in the infant's lungs at birth. OBJECTIVE: The goal
of this study was to determine the usefulness and accuracy of gastric aspirate
shake test for the diagnosis of two HMD. MATERIALS AND METHODS: This was a
diagnostic accuracy study carried out on 49 preterm infant born at Shahid
Sadoughi hospital in 2012 (25 newborns without pulmonary diseases and 24 newborns
with HMD). Shortly after birth, the shake test was performed using gastric fluid.
The results of the shake test were correlated with definitive diagnosis of HMD.
RESULTS: All infants who developed HMD had negative test results. In 23 of 25
infants with no respiratory distress, the test was positive. Our findings
indicated that the gastric aspirate shake test has 100% sensitivity, 92%
specificity, a 92.3% predictive value for surfactant deficiency, and 100%
predictive value for surfactant sufficiency. CONCLUSION: According to this study
gastric shake test (GST) is a reliable test and is a simple procedure to identify
those neonates who will develop respiratory distress syndrome (RDS) and therefore
to decide prophylactic exogenous surfactant replacement.
PMID- 25114672
TI - Ovarian stimulation medications and patients' responses as prognostic factors in
IUI-treated infertile Saudi patients.
AB - BACKGROUND: Intrauterine Insemination (IUI) remains the first thought of
infertility treatment. OBJECTIVE: To compare the stimulation effects and
Pregnancy rate (PR) outcomes of two ovulation induction (OI) medications, human
derived menopausal gonadotrophins (hMGH), Merional (MER), and recombinant
follicular stimulating hormone (rFSH), Puregon (PUR), in a cohort of Saudi
infertile patients, for better predictability of treatment results. MATERIALS AND
METHODS: During a 24-month period, 296 women underwent IUI single treatments.
PR's were correlated with the type of stimulation medication that were
prospectively and randomly assigned to each patient, and with the number and size
of maturing follicles detected on the hCG injection day. RESULTS: MER and PUR
needed comparable number of days (9.26+/-4.74 and 9.73+/-6.27 respectively)
before follicles were ready for IUI, although the average amount used from MER,
1199.90 IU, was about double that was used from PUR, 621.08 IU. The overall PR in
case of PUR however was nearly double that of MER, 13.28% and 7.14% respectively.
The best PR, 16.22%, occurred when the follicles matured within 12-13 days. Three
follicles of at least 15-mm diameter on the hCG day had better PR's than one or
two, however when the follicles' diameters were at least 18-mm, PR was
significantly higher, (p=0.013). CONCLUSION: MER and PUR had comparable
stimulation effects; however PUR had noticeably higher PR. The best PR occurred
when the follicles matured within 12-13 days. PR in case of three maturing
follicles on the hCG day was better than only one or two, and significantly
better when their diameters were at least 18 mm.
PMID- 25114673
TI - INSR gene variation is associated with decreased insulin sensitivity in Iraqi
women with PCOs.
AB - BACKGROUND: Polycystic ovarian syndrome (PCOS) is a complex, heterogeneous
disorder of uncertain etiology with strong genetic background. Insulin resistance
is present in the majority of PCOS cases with linkage and association between
single nucleotide polymorphisms of insulin receptor (INSR) gene and PCOS.
OBJECTIVE: To examine whether the exon 17 of INSR gene contributes to genetic
susceptibility to PCOS in Iraqi women and its effects on glucose tolerance test
and lipid profile. MATERIALS AND METHODS: Sixty-five healthy Iraqi women and
eighty-four infertile women with PCOS, divided into two subgroups depending on
the BMI were studied. Restriction fragment length polymorphism (RFLP-PCR)
analysis was performed to determine the genotypes for the His 1058 C/T
polymorphism at the tyrosine kinase domain in the INSR gene. Clinical,
anthropometric and biochemical parameters were also estimated. RESULTS: The C/T
polymorphism at His 1058 in exon 17 of INSR was associated with PCOS (obese and
non-obese). CC genotype frequency was higher in PCOS patients whereas TT genotype
was higher in control women. Those with CC genotype had higher BMI, GTT and lipid
profile than those with TT genotype. CONCLUSION: An association of C/T
polymorphism at His1058 of INSR with PCOS in Iraqi women was observed. Its
association with indices of insulin resistance and dyslipidemia were also
noticed.
PMID- 25114674
TI - Prevalence of Trichomonas vaginalis infection in Kashan city, Iran (2012-2013).
AB - BACKGROUND: Trichomonas vaginalis infection is one of the most common sexually
transmitted diseases in humans. T.vaginalis is a parasitic protozoan with a
predilection for human urogenital tract and causative agent for vaginitis,
cervicitis and urethritis in females. T.vaginalis infection is associated with
risk of Human Immunodeficiency Virus infectivity and pregnancy complication.
OBJECTIVE: In this study, the prevalence of T.vaginalis in individuals who
referred to public health units in Kashan city, Iran was investigated. MATERIALS
AND METHODS: This study was conducted on 970 women and 235 men who referred to 5
government health centers in Kashan, Iran during October 2012 to August 2013.
Demographic information was collected as per the study protocol. Vaginal
discharges and urine samples were obtained and examined by Trypticase-Yeast
Extract Maltose (TYM) culture medium and wet-mount methods. The prevalence of T.
vaginalis was determined using culture based method and wet-mount examinations.
RESULTS: The overall prevalence of trichomonal infection was 2% (95% CI, 2+/
0.08). The age of infected individual was 33.7+/-9.4 years. All of those
infected, were married housewives and 58.3% of them had primary school education.
No statistical correlation was observed between clinical manifestations and
parasitological results (p=0.8). CONCLUSION: This study showed a relatively low
prevalence of T.vaginalis infection in the study population. Since the clinical
signs of trichomoniasis are the same of other Sexually Transmitted Diseases
(STDs), confirmatory laboratory tests are necessary. Due to adverse outcomes of
disease, there is a great need for public education regarding implementation of
personal hygienic measures and prevention of inappropriate sexual contacts.
PMID- 25114675
TI - Evaluation of clinical factors influencing pregnancy rate in frozen embryo
transfer.
AB - BACKGROUND: Frozen embryo transfer (FET) is one of the most important
supplementary procedures in the treatment of infertile couples. While general
information concerning the outcome of fresh embryo transfer has been documented,
paucity of investigations has addressed the clinical factors influenced on
pregnancy rates in FET. OBJECTIVE: In this study, we performed a retrospective
analysis of clinical factors that potentially influence the outcome of FET.
MATERIALS AND METHODS: We reviewed the data from 372 women who were subjected to
FET registered from April 2009-2011 at the Research and clinical center, Shahid
Sadoughi University of Medical Sciences, Yazd, Iran. Baseline data and pregnancy
rate were collected. The data were analyzed statistically using the Kolmogorov
Smirnov, and Mann-Whitney tests. RESULTS: The clinical pregnancy rate was 57.7
and 29.2% in women <35 years old, and women >35 years old, respectively
(p<0.0001). Clinical pregnancy rates in women with FSH <10 IU/ml, and FSH >10
IU/ml were 56.3% and 17.5 %, respectively (p<0.0001). Whereas the other clinical
parameters consist of reason of fetus freezing, primary IVF protocol, IVF
procedure, endometrial thickness, treatment duration to fetal transfer found to
be unrelated to FET outcomes (p>0.05). CONCLUSION: Female age and basal FSH level
are the most important factors influencing the clinical pregnancy rate following
FET.
PMID- 25114676
TI - Feature and score fusion based multiple classifier selection for iris
recognition.
AB - The aim of this work is to propose a new feature and score fusion based iris
recognition approach where voting method on Multiple Classifier Selection
technique has been applied. Four Discrete Hidden Markov Model classifiers output,
that is, left iris based unimodal system, right iris based unimodal system, left
right iris feature fusion based multimodal system, and left-right iris likelihood
ratio score fusion based multimodal system, is combined using voting method to
achieve the final recognition result. CASIA-IrisV4 database has been used to
measure the performance of the proposed system with various dimensions.
Experimental results show the versatility of the proposed system of four
different classifiers with various dimensions. Finally, recognition accuracy of
the proposed system has been compared with existing N hamming distance score
fusion approach proposed by Ma et al., log-likelihood ratio score fusion approach
proposed by Schmid et al., and single level feature fusion approach proposed by
Hollingsworth et al.
PMID- 25114677
TI - IL1RN and KRT13 Expression in Bladder Cancer: Association with Pathologic
Characteristics and Smoking Status.
AB - Purpose. To validate microarray data on cytokeratin 13 (KRT13) and interleukin-1
receptor antagonist (IL1RN) expression in urothelial carcinoma of the urinary
bladder (UCB) and to correlate our findings with pathologic characteristics and
tobacco smoking. Methods. UCB tissue samples (n = 109) and control samples (n =
14) were obtained from transurethral resection and radical cystectomy specimens.
Immunohistochemical staining of KRT13 and IL1RN was performed and
semiquantitative expression scores were assessed. Smoking status was evaluated
using a standardized questionnaire. Expression scores were correlated with
pathologic characteristics (tumor stage and grade) and with smoking status.
Results. Loss of KRT13 and IL1RN expression was observed in UCB tissue samples
when compared to controls (P = 0.007, P = 0.008) in which KRT13 and IL1RN
expression were high. IL1RN expression was significantly reduced in muscle
invasive tumors (P = 0.003). In tissue samples of current smokers, a significant
downregulation of IL1RN was found when compared to never smokers (P = 0.013).
Conclusion. Decreased expressions of KRT13 and IL1RN are common features of UCB
and are associated with aggressive disease. Tobacco smoking may enhance the loss
of IL1RN, indicating an overweight of proinflammatory mediators involved in UCB
progression. Further validation of the influence of smoking on IL1RN expression
is warranted.
PMID- 25114678
TI - Pharmacophore Modeling and Molecular Docking Studies on Pinus roxburghii as a
Target for Diabetes Mellitus.
AB - The present study attempts to establish a relationship between
ethnopharmacological claims and bioactive constituents present in Pinus
roxburghii against all possible targets for diabetes through molecular docking
and to develop a pharmacophore model for the active target. The process of
molecular docking involves study of different bonding modes of one ligand with
active cavities of target receptors protein tyrosine phosphatase 1-beta (PTP
1beta), dipeptidyl peptidase-IV (DPP-IV), aldose reductase (AR), and insulin
receptor (IR) with help of docking software Molegro virtual docker (MVD). From
the results of docking score values on different receptors for antidiabetic
activity, it is observed that constituents, namely, secoisoresinol, pinoresinol,
and cedeodarin, showed the best docking results on almost all the receptors,
while the most significant results were observed on AR. Then, LigandScout was
applied to develop a pharmacophore model for active target. LigandScout revealed
that 2 hydrogen bond donors pointing towards Tyr 48 and His 110 are a major
requirement of the pharmacophore generated. In our molecular docking studies, the
active constituent, secoisoresinol, has also shown hydrogen bonding with His 110
residue which is a part of the pharmacophore. The docking results have given
better insights into the development of better aldose reductase inhibitor so as
to treat diabetes related secondary complications.
PMID- 25114679
TI - The Association between IGF-1 Polymorphisms, IGF-1 Serum Levels, and Cognitive
Functions in Healthy Adults: The Amsterdam Growth and Health Longitudinal Study.
AB - Several studies have demonstrated an association between polymorphisms in the
insulin-like growth factor-1 (IGF-1) gene and IGF-1 serum levels. IGF-1 levels
have been associated with cognitive functioning in older persons and growth
hormone deficient patients. The present study investigates whether IGF-1
polymorphisms, IGF-1 levels, and cognition are interconnected in healthy adults.
Data of 277 participants (mean age: 42.4 years) of the Amsterdam Growth and
Health Longitudinal Study on IGF-1 promoter polymorphisms, IGF-1 serum level,
spatial working memory (SWM), paired associate learning (PAL), and IQ tests were
analyzed. (M)ANOVAs were applied to confirm the associations between IGF-1
polymorphisms and IGF-1 levels and between IGF-1 levels and cognition. Three
groups were distinguished based on specific IGF-1 polymorphism alleles: a
homozygote 192 bp/192 bp genotype, a heterozygote 192 bp/x genotype, and a
noncarrier x/x genotype. Although different IGF-1 levels were found for the three
genotypes, performance on all cognitive tasks and IQ measures was similar.
Despite the associations between IGF-1 polymorphisms and IGF-1 levels, no
association was found between cognition and IGF-1 levels. It seems that IGF-1
does not play a role in the cognitive performance of healthy middle-aged adults.
Possible, IGF-1 fulfills a more developmental and protective role in cognition
which becomes apparent during childhood, old-age, or disease.
PMID- 25114681
TI - Response to initial therapy of differentiated thyroid cancer predicts the long
term outcome better than classical risk stratification systems.
AB - Objective. Although differentiated thyroid cancer (DTC) usually has an indolent
course, some cases show a poor prognosis; therefore, risk stratification is
required. The objective of this study is to compare the predictive ability of
classical risk stratification systems proposed by the European Thyroid
Association (ETA) and American Thyroid Association (ATA) with the system proposed
by Tuttle et al. in 2010, based on the response to initial therapy (RIT).
Methods. We retrospectively reviewed 176 cases of DTC with a median follow-up
period of 7.0 years. Each patient was stratified using ETA, ATA, and RIT systems.
Negative predictive value (NPV) and positive predictive value (PPV) were
determined. The area under receiver operating characteristic (ROC) curve was
calculated in order to compare the predictive ability. Results. RIT showed a NPV
of 97.7%, better than NPV of ETA and ATA systems (93.9% and 94.9%, resp.). ETA
and ATA systems showed poor PPV (40.3% and 41%, resp.), while RIT showed a PPV of
70.8%. The area under ROC curve was 0.7535 for ETA, 0.7876 for ATA, and 0.9112
for RIT, showing statistical significant differences (P < 0.05). Conclusions. RIT
predicts the long-term outcome of DTC better than ETA/ATA systems, becoming a
useful system to adapt management strategies.
PMID- 25114680
TI - ATP Synthase beta-Chain Overexpression in SR-BI Knockout Mice Increases HDL
Uptake and Reduces Plasma HDL Level.
AB - HDL cholesterol is known to be inversely correlated with cardiovascular disease
due to its diverse antiatherogenic functions. SR-BI mediates the selective uptake
of HDL-C. SR-BI knockout diminishes but does not completely block the transport
of HDL; other receptors may be involved. Ectopic ATP synthase beta-chain in
hepatocytes has been previously characterized as an apoA-I receptor, triggering
HDL internalization. This study was undertaken to identify the overexpression of
ectopic ATP synthase beta-chain on DIL-HDL uptake in primary hepatocytes in vitro
and on plasma HDL levels in SR-BI knockout mice. Human ATP synthase beta-chain
cDNA was delivered to the mouse liver by adenovirus and GFP adenovirus as
control. The adenovirus-mediated overexpression of beta-chain was identified at
both mRNA and protein levels on mice liver and validated by its increasing of DiL
HDL uptake in primary hepatocytes. In response to hepatic overexpression of beta
chain, plasma HDL-C levels and cholesterol were reduced in SR-BI knockout mice,
compared with the control. The present data suggest that ATP synthase beta-chain
can serve as the endocytic receptor of HDL, and its overexpression can reduce
plasma HDL-C.
PMID- 25114682
TI - Body Mass Index Is Associated with Hypercholesterolemia following Thyroid Hormone
Withdrawal in Thyroidectomized Patients.
AB - Thyroid hormone withdrawal (THW) for postoperative radioiodine adjuvant therapy
or diagnostic radioiodine whole body scan in patients with differentiated thyroid
cancers results in acute thyroid hormone deficiency and abnormal lipid profiles.
To better clarify the clinical pattern of dyslipidemia occurring after THW, we
retrospectively analyzed the association between serum total cholesterol level
after THW and various clinical factors in a total of 61 patients who underwent
total thyroidectomy due to papillary thyroid cancers from January 2010 to March
2012, in Severance Hospital, Seoul, Korea. Preoperative baseline total
cholesterol was significantly correlated with post-THW total cholesterol level;
however, age, gender, or elevated TSH level after THW itself was not correlated
with post-THW total cholesterol level. A significant correlation between
preoperative measured BMI and post-THW total cholesterol level was found (r =
0.263, P = 0.041). In multiple logistic analysis, BMI was an independent
determining factor of post-THW total cholesterol level (P = 0.012).
PMID- 25114683
TI - Computer-based diagnostic expert systems in rheumatology: where do we stand in
2014?
AB - Background. The early detection of rheumatic diseases and the treatment to target
have become of utmost importance to control the disease and improve its
prognosis. However, establishing a diagnosis in early stages is challenging as
many diseases initially present with similar symptoms and signs. Expert systems
are computer programs designed to support the human decision making and have been
developed in almost every field of medicine. Methods. This review focuses on the
developments in the field of rheumatology to give a comprehensive insight.
Medline, Embase, and Cochrane Library were searched. Results. Reports of 25
expert systems with different design and field of application were found. The
performance of 19 of the identified expert systems was evaluated. The proportion
of correctly diagnosed cases was between 43.1 and 99.9%. Sensitivity and
specificity ranged from 62 to 100 and 88 to 98%, respectively. Conclusions.
Promising diagnostic expert systems with moderate to excellent performance were
identified. The validation process was in general underappreciated. None of the
systems, however, seemed to have succeeded in daily practice. This review
identifies optimal characteristics to increase the survival rate of expert
systems and may serve as valuable information for future developments in the
field.
PMID- 25114685
TI - Postpartum ovarian vein and inferior vena cava thrombosis.
AB - Postpartum ovarian vein thrombosis (POVT), which generally occurs 2-15 days
postpartum, is a rare complication. It can be confused with acute appendicitis,
pelvic infection, ovarian torsion, tubo-ovarian abscess, and pyelonephritis. It
is associated with morbidity and mortality. Here, we present a patient with
postpartum OVT and IVC diagnosed by US and CT findings. She was treated
successfully with no further need for any interventional procedures.
PMID- 25114684
TI - HBV Reactivation in Patients Treated with Antitumor Necrosis Factor-Alpha (TNF
alpha) Agents for Rheumatic and Dermatologic Conditions: A Systematic Review and
Meta-Analysis.
AB - Introduction. Antitumor necrosis factor-alpha (TNF-alpha) agents are widely used
for treatment of rheumatic and dermatological diseases. We conducted the
systematic review and meta-analysis to assess the prevalence of HBV reactivation
among patients treated with anti-TNF-alpha. Methods and Findings. A comprehensive
literature search of MEDLINE, Scopus, and ISI Web of Knowledge databases was
conducted. From 21 studies included in the systematic review, 9 included patients
with occult chronic HBV infection and 6 included patients with overt infection
while 6 addressed both groups. Based on 10 studies eligible for meta-analysis we
report pooled estimate of HBV reactivation of 4.2% (95% CI: 1.4-8.2%, I (2):
74.7%). The pooled prevalence of reactivation was 3.0% (95% CI: 0.6-7.2, I (2):
77.1%) for patients with occult infection, and 15.4% (95% CI: 1.2-41.2%, I (2):
79.9%) for overt infection. The prevalence of reactivation was 3.9% (95% CI: 1.1
8.4%, I (2): 51.1%) for treatment with etanercept and 4.6% (95% CI: 0.5-12.5%, I
(2): 28.7%) for adalimumab. For subgroup of patients without any antiviral
prophylaxis the pooled reactivation was 4.0% (95% CI: 1.2-8.3%, I (2): 75.6%).
Conclusion. Although HBV reactivation rate is relatively low in patients treated
with anti-TNF-alpha for rheumatic and dermatological conditions, the antiviral
prophylaxis would be recommended in patients with overt chronic HBV infection.
PMID- 25114687
TI - Giant solitary fibrous tumor of the parotid gland.
AB - Solitary fibrous tumors (SFTs) are rare tumors that are mostly found arising from
the pleura. SFT of the parotid gland is a rare tumor; only a few cases have been
described in the literature. SFTs are benign in most cases. Clinically, SFTs
usually manifest as well circumscribed, slow-growing, smooth, and painless
masses. CT-Scan and MRI are the most sensitive imaging procedures used. The
treatment of choice is complete surgical excision of the lesion. Since recurrence
and metastasis can take place after several years, a lifelong clinical and
imaging regular follow-up is compulsory. In this paper, we describe the
diagnostic and therapeutic challenges of the up-to-now biggest parotid SFT. The
clinical presentation, surgical management, and pathological and
immunohistochemistry findings are described.
PMID- 25114686
TI - Wolff-Parkinson-white syndrome mimics a conduction disease.
AB - Background. It is important to recognise Wolff-Parkinson-White (WPW) syndrome in
electrocardiograms (ECG), as it may mimic ischaemic heart disease, ventricular
hypertrophy, and bundle branch block. Recognising WPW syndrome allows for risk
stratification, the identification of associated conditions, and the institution
of appropriate management. Objective. The present case showed that
electrophysiological study is indicated in patients with abnormal ECG and
syncope. Case Report. A 40-year-old man with Wolff-Parkinson-White syndrome was
presented to emergency with syncope. A baseline ECG was a complete right branch
block and posterior left hemiblock. He was admitted to the cardiac care unit for
pacemaker implantation. The atypical figure of complete right branch block and
posterior left hemiblock was thought to be a "false positive" of conduction
abnormality. But the long anterograde refractory period of the both accessory
pathway and atrioventricular conduction may cause difficulty in diagnosing Wolff
Parkinson-White syndrome, Conclusion. A Wolff-Parkinson-White Syndrome may mimic
a conduction disease. No reliable algorithm exists for making an ECG diagnosis of
a preexcitation syndrome with conduction disorders. This can lead to diagnostic
and therapeutic dilemmas in the context of syncope.
PMID- 25114688
TI - Clinical presentation and magnetic resonance findings in sellar tuberculomas.
AB - Background and Importance. Sellar tuberculomas are extremely rare lesions with
nonspecific clinical manifestations. The tuberculous infection of the pituitary
gland and sellar region is characterized by the presence of an acute or chronic
inflammatory reaction and may occur in the absence of systemic tuberculosis. The
diagnosis is difficult prior to the surgery. An adequate diagnostic and
antituberculous drugs usually result in a good outcome. Clinical Presentation. We
report four cases of sellar tuberculoma, 3/1 female/male, age range: 50-57 years.
All patients had visual disturbances and low levels of cortisol. Conclusion. The
clinical diagnosis of sellar tuberculoma is a challenge and should be suspected
when a sellar lesion shows abnormal enhancement pattern and stalk involvement,
and absence of signal suppression in FLAIR.
PMID- 25114689
TI - Comprehensive understanding of atrial septal defects by imaging studies for
successful transcatheter closure.
AB - Transcatheter closure of atrial septal defects has become a popular procedure.
The availability of a preprocedural imaging study is crucial for a safe and
successful closure. Both the anatomy and morphology of the defect should be
precisely evaluated before the procedure. Three-dimensional (3D) echocardiography
and cardiac computed tomography are helpful for understanding the morphology of a
defect, which is important because different defect morphologies could variously
impact the results. During the procedure, real-time 3D echocardiography can be
used to guide an accurate closure. The safety and efficiency of transcatheter
closures of atrial septal defects could be improved through the use of detailed
imaging studies.
PMID- 25114691
TI - Prader-Willi syndrome: a single center's experience in Korea.
AB - PURPOSE: Prader-Willi syndrome (PWS) is a complex genetic disorder that results
from the lack of paternally expressed genes in the chromosome 15q11-q13 region.
This study was performed to delineate the clinical features of PWS infants and
toddlers and the effects of two-year growth hormone (GH) treatment according to
gender and age at the start of treatment. METHODS: The clinical characteristics
and the results of the GH treatment were reviewed retrospectively for 30 PWS
patients diagnosed by molecular genetic testing and clinical manifestations.
RESULTS: The mean age at diagnosis with PWS was 13.7 months (2-47 months of age).
All patients showed the characteristics of facial dysmorphism, including brown
hair and almond-shaped eyes. Most patients showed developmental delays/mental
retardation (93.3%), cryptorchidism (75%), feeding problems in infancy (73.3%),
and neonatal or infantile hypotonia (66.7%). Among 30 patients, 14 PWS infants
and toddlers had been treated with GH for more than two years. Two years of GH
treatment resulted in an improvement in head circumference-standard deviation
score (HC-SDS), body weight-SDS, insulin-like growth factor-1 (IGF-1) SDS, IGF
binding protein-3 (IGFBP-3) SDS, lean body mass, and bone mineral content,
especially in IGFBP-3 SDS and motor development in PWS patients younger than two
years of age. There was significant increase in IGF-1 SDS and IGFBP-3 SDS among
male PWS patients after GH treatment. CONCLUSION: Our study showed increases in
IGFBP-3 SDS and an improvement in motor development among individuals under two
years of age after GH treatment, and significant difference in IGF-1 SDS and
IGFBP-3 SDS by gender.
PMID- 25114690
TI - Benign convulsion with mild gastroenteritis.
AB - Benign convulsion with mild gastroenteritis (CwG) is a type of afebrile seizure
that occurs in children. CwG is defined as a convulsion in a previously healthy
child with no known central nervous system infection or encephalopathy,
accompanying mild diarrhea without fever, electrolyte imbalance, or moderate to
severe dehydration. Convulsions in CwG are characterized by multiple brief
episodes of generalized or focal seizures. Although the etiology and
pathophysiology have yet to be fully explained, many pathogenic mechanisms have
been proposed including the possibility of direct invasion of the central nervous
system by a gastrointestinal virus such as rotavirus or the possibility of
indirect influence by the production and effects of certain mediators. The
electroencephalogram findings are benign and long-term antiepileptic treatment is
typically not required. Long-term prognosis has been favorable with normal
psychomotor development. This review provides a general overview of CwG with the
goal of allowing physicians practicing in the field of pediatrics to better
recognize this unique entity and, ultimately, to minimize unnecessary evaluation
and treatment.
PMID- 25114692
TI - Prevalence of restless legs syndrome and sleep problems in Korean children and
adolescents with attention deficit hyperactivity disorder: a single institution
study.
AB - PURPOSE: Attention deficit hyperactivity disorder (ADHD) is a common disorder in
school-aged children. Patients with restless legs syndrome (RLS) often present
with ADHD symptoms and vice versa. This study was the first to attempt to
identify the prevalence of RLS and sleep problems in children with ADHD in Korea.
METHODS: Patients diagnosed with ADHD were asked to complete a sleep
questionnaire. The sleep questionnaire included items to help identify the
presence of four typical symptoms that are used as diagnostic criteria for RLS.
RESULTS: A total of 56 patients, including 51 boys and 5 girls (mean age, 10.7
years old) participated. Of these, 24 complained of pain, discomfort, or an
unpleasant sensation in the legs. Based on the RLS diagnostic criteria, 2
patients were diagnosed with definite RLS and 4 with probable RLS. There were no
significant differences in age, medication dosage, or neuropsychological test
scores between the patients with and without RLS symptoms. CONCLUSION:
Approximately 42.9% of patients with ADHD presented with RLS symptoms and 7.1% of
these were diagnosed with RLS. Patients with ADHD also experienced various other
sleep disorders. Thus, appropriate assessment and treatment for sleep disorders
in patients with ADHD is essential.
PMID- 25114693
TI - Articulation error of children with adenoid hypertrophy.
AB - PURPOSE: Adenoid hypertrophy is a physical alteration that may affect speech, and
a speech disorder can have other negative effects on a child's life. Airway
obstruction leads to constricted oral breathing and causes postural alterations
of several oro-facial structures, including the mouth, tongue, and hyoid bone.
The postural modifications may affect several aspects of speech production.
METHODS: In this study, we compared articulation errors in 19 children with
adenoid hypertrophy (subject group) to those of 33 children with functional
articulation disorders independent of anatomical problems (control group).
RESULTS: The mean age of the subject group was significantly higher (P=0.016).
Substitution was more frequent in the subject group (P=0.003; odds ratio [OR],
1.80; 95% confidence interval [CI], 1.23-2.62), while omission was less frequent
(P<0.001; OR, 0.43; 95% CI, 0.27-0.67). Articulation errors were significantly
less frequent in the palatal affricative in the subject group (P=0.047; OR, 0.25;
95% CI, 0.07-0.92). The number of articulation errors in other consonants was not
different between the two groups. Nasalization and aspiration were significantly
more frequent in the subject group (P=0.007 and 0.014; OR, 14.77 and 0.014; 95%
CI, [1.62-135.04] and NA, respectively). Otherwise, there were no differences
between the two groups. CONCLUSION: We identified the characteristics of
articulation errors in children with adenoid hypertrophy, but our data did not
show the relationship between adenoid hypertrophy and oral motor function that
has been observed in previous studies. The association between adenoid
hypertrophy and oral motor function remains doubtful.
PMID- 25114694
TI - Asymptomatic maternal 3-methylcrotonylglycinuria detected by her unaffected
baby's neonatal screening test.
AB - 3-methylcrotonyl-coenzyme A carboxylase (3MCC) deficiency is an autosomal
recessive disorder in which leucine catabolism is hampered, leading to increased
urinary excretion of 3-methylcrotonylglycine. In addition, 3
hydroxyisovalerylcarnitine levels increase in the blood, and the elevated levels
form the basis of neonatal screening. 3MCC deficiency symptoms are variable,
ranging from neonatal onset with severe neurological abnormality to a normal,
asymptomatic phenotype. Although 3MCC deficiency was previously considered to be
rare, it has been found to be one of the most common metabolic disorders in
newborns after the neonatal screening test using tandem mass spectrometry was
introduced. Additionally, asymptomatic 3MCC deficient mothers have been
identified due to abnormal results of unaffected baby's neonatal screening test.
Some of the 3MCC-deficient mothers show symptoms such as fatigue, myopathy, or
metabolic crisis with febrile illnesses. In the current study, we identified an
asymptomatic 3MCC deficient mother when she showed abnormal results during a
neonatal screening test of a healthy infant.
PMID- 25114695
TI - Atypical teratoid rhabdoid brain tumor in an infant with ring chromosome 22.
AB - Reports of constitutional ring chromosome 22, r(22) are rare. Individuals with
r(22) present similar features as those with the 22q13 deletion syndrome. The
instability in the ring chromosome contributes to the development of variable
phenotypes. Central nervous system (CNS) atypical teratoid rhabdoid tumors
(ATRTs) are rare, highly malignant tumors, primarily occurring in young children
below 3 years of age. The majority of ATRT cases display genetic alterations of
SMARCB1 (INI1/hSNF5), a tumor suppressor gene located on 22q11.2. The coexistence
of a CNS ATRT in a child with a r(22) is rare. We present a case of a 4-month-old
boy with 46,XY,r(22)(p13q13.3), generalized hypotonia and delayed development.
High-resolution microarray analysis revealed a 3.5-Mb deletion at 22q13.31q13.33.
At 11 months, the patient had an ATRT (5.6 cm*5.0 cm*7.6 cm) in the cerebellar
vermis, which was detected in the brain via magnetic resonance imaging.
PMID- 25114696
TI - Diagnosis of pulmonary tuberculosis and nontuberculous mycobacterial lung disease
in Korea.
AB - The recovery of nontuberculous mycobacteria (NTM) from respiratory specimens and
the number of patients with NTM lung disease have been rapidly increasing in
Korea. An early differential diagnosis of NTM lung disease from pulmonary
tuberculosis (TB) is important, as the therapeutic regimen differs from that of
pulmonary TB, and it is not necessary to track the contacts of patients with NTM
lung disease. However, differentiating NTM lung disease from pulmonary TB remains
difficult, because the clinical presentations of the two diseases are similar and
a definite diagnosis of NTM lung disease based on sputum culture takes time. This
review focuses on the changing epidemiology, clinical and radiographic
manifestation, and laboratory diagnosis of pulmonary TB and NTM lung disease in
Korea.
PMID- 25114697
TI - Clinical year in review 2014: critical care medicine.
AB - Severe sepsis is the most common cause of death among critically ill patients in
non-coronary intensive care units. In 2002, the guideline titled "Surviving
Sepsis Campaign" was published by American and European Critical Care Medicine to
decrease the mortality of severe sepsis and septic shock patients, which has been
the basis of the treatment for those patients. After the first revised guidelines
were published on 2008, the most current version was published in 2013 based on
the updated literature of until fall 2012. Other important revised guidelines in
critical care field such as 'Clinical Practice Guidelines for the Management of
Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit' were
revised in 2013. This article will review the revised guidelines and several
additional interesting published papers of until March 2014, including the part
of ventilator-induced lung injury and the preventive strategies.
PMID- 25114698
TI - Outcomes of second-line chemotherapy for advanced non-small cell lung cancer in
one institution.
AB - BACKGROUND: This study analyzed the negative prognostic factors in patients who
received second-line chemotherapy for advanced inoperable non-small cell lung
cancer (NSCLC). METHODS: We retrospectively reviewed the records of 137 patients
with inoperable stage III-IV NSCLC who received second-line chemotherapy. The
effects of clinical parameters on survival were analyzed and the hazard ratios
(HR) for mortality were identified by a Cox regression analysis. RESULTS: Sex,
age older than 65 years, smoking history, cell type, T-stage, best response to
first-line chemotherapy and first-line chemotherapy regimen were significant
negative predictors in univariate analysis. The multivariate analysis showed that
patients older than 65 years (HR, 1.530; 95% confidence interval [CI], 1.020
2.297), advanced T stage (T4 vs. T1; HR, 2.273; 95% CI, 1.010-5.114) and non
responders who showed progression with first-line chemotherapy (HR, 1.530; 95%
CI, 1.063-2.203) had higher HR for death. CONCLUSION: The age factor, T stage and
responsiveness to first-line chemotherapy were important factors in predicting
the outcome of patients with advanced NSCLC who received second-line
chemotherapy. The results may help to predict outcomes for these patients in the
future.
PMID- 25114699
TI - Annual Change in Pulmonary Function and Clinical Characteristics of Combined
Pulmonary Fibrosis and Emphysema and Idiopathic Pulmonary Fibrosis: Over a 3-Year
Follow-up.
AB - BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) have different
pulmonary function tests (PFTs) and outcomes than idiopathic pulmonary fibrosis
(IPF). The intention of this study was to identify unknown differences between
CPFE and IPF by a retrospective comparison of clinical data including baseline
and annual changes in pulmonary function, comorbidities, laboratory findings,
clinical characteristics and cause of hospitalization. METHODS: This study
retrospectively enrolled patients with CPFE and IPF who had undergone PFTs once
or several times per year during a follow-up period of three years. Baseline
clinical characteristics and the annual changes in the pulmonary function during
the follow-up period were compared between 26 with CPFE and 42 patients with IPF.
RESULTS: The baseline ratio of forced expiratory volume in one second to forced
vital capacity (FEV1/FVC%) in patients with CPFE was lower than that in patients
with IPF (78.6+/-1.7 vs. 82.9+/-1.1, p=0.041). The annual decrease in FEV1/FVC in
the CPFE was significantly higher than in the IPF. The annual decreases in
diffusion capacity of carbon monoxide and FVC showed no significant differences
between the two groups. The symptom durations of cough and sputum were in the
CPFE significantly lower than in the IPF. The serum erythrocyte sedimentation
rate level at the acute stage was significantly higher than in the IPF. There
were no significant differences in the hospitalization rate and pneumonia was the
most common cause of hospitalization in both study groups. CONCLUSION: The annual
decrease of FEV1/FVC was in patients with CPFE significantly higher than in the
patients with IPF.
PMID- 25114700
TI - Takotsubo cardiomyopathy caused by pulmonary tuberculosis: a case report.
AB - Takotsubo cardiomyopathy (TTC) is defined as a reversible, acute ventricular
dysfunction without any evidence of coronary artery obstruction. There have been
reports of TTC caused by emotional or physical stress, drug use, hormone
imbalance, or medical conditions such as pulmonary disease, sepsis, and trauma,
but a relationship between TTC and pulmonary tuberculosis has not previously been
reported. From our knowledge, this is the first report of TTC caused by pulmonary
tuberculosis.
PMID- 25114701
TI - A case of invasive pulmonary aspergillosis with direct invasion of the
mediastinum and the left atrium in an immunocompetent patient.
AB - We report a case of invasive pulmonary aspergillosis invading the mediastinum and
the left atrium. A 70-year-old woman was hospitalized for dyspnea. She had been
well controlled for her diabetes mellitus and hypertension. The chest X-ray
disclosed mediastinal widening, and the computed tomography scan of the chest
showed that there was a large mediastinal mass and this lesion extended into the
left atrium and right bronchus. The cardiac echocardiography showed that a huge
mediastinal cystic mass compressed in the right atrium and a hyperechoic polypoid
lesion in the left. The pathology from the bronchoscopic biopsy observed abundant
fungal hyphae which was stained with periodic acid-Schiff and Gomori's
methenamine silver. Despite the treatment with antifungal agents, she died from
cardiac tamponade after three months. Invasive pulmonary aspergillosis, which
involves the mediastinum and the heart, is very rare in immunocompetent patients.
PMID- 25114702
TI - Multiple hypercoagulability disorders at presentation of non-small-cell lung
cancer.
AB - Hypercoagulability disorders are commonly encountered in clinical situations in
patients with a variety of cancers. However, several hypercoagulability disorders
presenting as first symptoms or signs in cancer patients have rarely been
reported. We herein described a case of a woman with adenocarcinoma of the lung
presenting with deep vein thrombosis, nonbacterial thrombotic endocarditis,
recurrent cerebral embolic infarction, and heart failure.
PMID- 25114703
TI - A case of lung carcinoma with rhabdoid phenotype mimicking an aspergilloma in
patient with recurrent hemoptysis.
AB - Malignant rhabdoid tumor was first discovered in the kidney, and rhabdoid tumor
of the lung was first reported in 1995. These were included as the variants of
large-cell carcinoma, according to the 1999 World Health Organization
classification of lung tumors. The rhabdoid tumor of the lung exhibits aggressive
biological behavior and has a poor prognosis, and only a few reports of this
tumor exist. We report a case of lung carcinoma with a rhabdoid phenotype,
initially misdiagnosed as an aspergilloma, in a 48-year-old man who presented
with recurrent hemoptysis. The chest computed tomography scans showed a huge
consolidative lesion with an air crescent sign in the left upper lung and no
contrast-enhancing lesion. An aspergilloma was diagnosed by the radiologist.
However, after surgical excision and pathological examination, rhabdoid carcinoma
was diagnosed. A surgical resection helps to make it possible to pathologically
distinguish a malignancy from an aspergilloma.
PMID- 25114705
TI - Analgesia Synergism of Essential Oil from Pericarp of Zanthoxylum schinifolium
and Verapamil.
AB - Objective. To evaluate the synergistic analgesic effect of essential oil of
Zanthoxylum schinifolium Sieb. et Zucc. (EOZ) and verapamil (Ver). Method. The
qualitative and quantitative composition of EOZ were determined with gas
chromatography/Mass spectrometer. The interaction between EOZ and Ver in
antinociceptive activity was evaluated by using acetic acid-induced writhing, hot
plate, and tail flick tests in mice and in isolated toad sciatic nerve test.
Results. Linalool, limonene, and sabinene are the major components of EOZ. EOZ
(middle-dose: 40 mg.kg(-1), high-dose: 80 mg.kg(-1)) and EOZ + Ver (Each dose
group) have remarkable analgesic effects on pain in mice induced by acetic acid
induced writhing, hot plate, and tail flick tests. Low-dose EOZ (20 mg.kg(-1))
had no analgesic action, but when it is combined with Ver it has shown
significant antinociception. Verapamil has a faint analgesic effect but was not
able to inhibit action potential transmission in toad sciatic nerve. EOZ (0.2%)
and EOZ + Ver (0.2% + 0.05%) also inhibited action potential transmission in toad
sciatic nerve. Combination of EOZ with Ver had a greater analgesic effect and
inhibition of nerve action potential transmission compared to its components EOZ
and Ver. Conclusion. The combination of EOZ with Ver produces a synergistic
analgesic effect.
PMID- 25114704
TI - Miniscalpel-Needle versus Steroid Injection for Plantar Fasciitis: A Randomized
Controlled Trial with a 12-Month Follow-Up.
AB - Plantar fasciitis is the most common cause of heel pain in adults. A novel
alternative medical instrument, the miniscalpel-needle (MSN), which is based on
an acupuncture needle, has been recently developed in China. The objective of
this study was to evaluate the effectiveness of the MSN release treatment versus
that of traditional steroid injection for plantar fasciitis. Patients with
plantar fasciitis were randomly assigned to 2 groups and followed up for 12
months, with 29 receiving MSN treatment and 25 receiving steroid injection
treatment. The results showed that visual analog scale scores for morning pain,
active pain, and overall heel pain all were decreased significantly in the MSN
group from 1 to 12 months after treatment. In contrast, treatment with steroid
injection showed a significant effect only at the 1-month follow-up but not at 6
or 12 months after treatment. Moreover, the MSN group achieved more rapid and
sustained improvements than the steroid group throughout the duration of this
study. No severe side effects were observed with MSN treatment. Our data suggest
that the MSN release treatment is safe and has a significant benefit for plantar
fasciitis compared to steroid injection.
PMID- 25114706
TI - The Comparative Study on Expression of SIRT1 Signal Transduction by Xuefuzhuyu
Capsule.
AB - The Xuefuzhuyu capsule (XFZY) is widely used for the treatment of ischemic heart
disease (IHD) in China. We previously demonstrated that XFZY could reduce
apoptosis in Sprague-Dawley rat cardiomyocytes with the similar effect of
resveratrol (Res) Hori et al. (2013), although its molecular mechanism underlying
this protective effect is still unclear. Silent information regulator of
transcription 1 (SIRT1) had been demonstrated to be responsible for
cardioprotection against ischemia-reperfusion injury via long-term
transcriptionally regulatory mechanism Braunersreuther and Jaquet (2012).
Therefore, in the present study, we aimed to test if XFZY might contribute to the
protection of ischemic myocardial cells induced by ischemia through SIRT1
mediated signal transduction pathway by using electron micrograph, RT-PCR assay,
and western-blot test. All the result showed that the target genes of SIRT1
pathway including P53, NF-kB, FOXO1, FOXO3, and FOXO4 were significantly
downregulated to SIRT1, suggesting that apoptosis pathway might transcriptionally
be regulated to SIRT1. In addition, the expression level of SIRT1 was
significantly increased by XFZ, it might prove that SIRT1 is the target of XFZY
working on ischemia heart disease. Our findings supported that XFZY might
function to protect myocardial cells and reduce myocardial injury though SIRT1
signaling pathway and has the same pharmacological effect with Res.
PMID- 25114707
TI - Acupuncture and depth: future direction for acupuncture research.
AB - The research on acupuncture has increased steadily over the years and regular
review and revision of the direction of future acupuncture research are
necessary. This paper aims to review and explore the significance of acupuncture
depth in modern acupuncture research. Searches conducted in Science Direct and
China National Knowledge Infrastructure (CNKI) databases reflected a lack of
focus on depth of acupuncture. We propose that the research trends of acupuncture
should progress to the depth of insertion. It is suggested that future
acupuncture research, especially randomized controlled trials (RCTs), should take
into consideration the depth of insertion. Comparison between databases using
different language of medium suggests the need for international collaboration of
researchers from the same field. It is also crucial to inherit and innovate
traditional medicine (TM) through modern technology. The use of bibliometric
method is also suitable for development of TM research trends. Acupuncture and
depth should be considered as one of the future directions of acupuncture
research.
PMID- 25114708
TI - Identification of chinese herbal medicines from zingiberaceae family using
feature extraction and cascade classifier based on response signals from e-nose.
AB - Identification of Chinese herbal medicines (CHMs) by human experience is often
inaccurate because individual ability and external factors may influence the
outcome. However, it might be promising to employ an electronic nose (E-nose) to
identify them. This paper presents a rapid and reliable method for identification
of ten different species of CHMs from Zingiberaceae family based on their
response signals from E-nose. Ten Zingiberaceae CHMs were measured and their
maximum response values were analyzed by principal component analysis (PCA).
Result shows that E Zhu (Curcuma phaeocaulis Val.) and Yi Zhi (Alpinia oxyphylla
Miq.) could not be distinguished completely by PCA. Two solutions were proposed:
(i) using BestFirst+CfsSubsetEval (BC) method to extract more discriminative
features to select sensors with higher contribution rate and remove the redundant
signals; (ii) employing a novel cascade classifier with two stages to enhance the
distinguishing-positive rate (DPR). Based on these strategies, six features were
extracted and used in different stages of the cascade classifier with higher
DPRs.
PMID- 25114709
TI - Effects of young barley leaf powder on gastrointestinal functions in rats and its
efficacy-related physicochemical properties.
AB - Young barley leaf is consumed as a popular green-colored drink, which is named
"Aojiru" in Japan. In the present study, we examined effects of young barley leaf
powder (BL) on gastrointestinal transit time (GTT) and fecal moisture and weight
in comparison with wheat bran (WB) in male Sprague-Dawley rats. In addition, an
attempt was made to identify BL components responsible for these effects by using
various fractions of BL. Additionally, we examined the water-holding capacity and
setting volume of BL in vitro. We also examined the granular structures of BL
with a scanning electron microscope. As a result, BL supplementation in the diet
increased the fecal weight and shortened GTT. Our results demonstrate that the
active component responsible for the effect on increasing the fecal volume in BL
is the water-insoluble dietary fiber fraction and that this effect is thought to
be caused by stimulation of the gut tract by the pH lowering. Furthermore, the
high laxative action of BL was thought to be ascribable to the high water-holding
capacity due to the complicated structures of BL.
PMID- 25114710
TI - Sudachitin, a polymethoxylated flavone, improves glucose and lipid metabolism by
increasing mitochondrial biogenesis in skeletal muscle.
AB - BACKGROUND: Obesity is a major risk factor for insulin resistance, type 2
diabetes, and stroke. Flavonoids are effective antioxidants that protect against
these chronic diseases. In this study, we evaluated the effects of sudachitin, a
polymethoxylated flavonoid found in the skin of the Citrus sudachi fruit, on
glucose, lipid, and energy metabolism in mice with high-fat diet-induced obesity
and db/db diabetic mice. In our current study, we show that sudachitin improves
metabolism and stimulates mitochondrial biogenesis, thereby increasing energy
expenditure and reducing weight gain. METHODS: C57BL/6 J mice fed a high-fat diet
(40% fat) and db/db mice fed a normal diet were treated orally with 5 mg/kg
sudachitin or vehicle for 12 weeks. Following treatment, oxygen expenditure was
assessed using indirect calorimetry, while glucose tolerance, insulin
sensitivity, and indices of dyslipidemia were assessed by serum biochemistry.
Quantitative polymerase chain reaction was used to determine the effect of
sudachitin on the transcription of key metabolism-regulating genes in the
skeletal muscle, liver, and white and brown adipose tissues. Primary myocytes
were also prepared to examine the signaling mechanisms targeted by sudachitin in
vitro. RESULTS: Sudachitin improved dyslipidemia, as evidenced by reduction in
triglyceride and free fatty acid levels, and improved glucose tolerance and
insulin resistance. It also enhanced energy expenditure and fatty acid beta
oxidation by increasing mitochondrial biogenesis and function. The in vitro assay
results suggest that sudachitin increased Sirt1 and PGC-1alpha expression in the
skeletal muscle. CONCLUSIONS: Sudachitin may improve dyslipidemia and metabolic
syndrome by improving energy metabolism. Furthermore, it also induces
mitochondrial biogenesis to protect against metabolic disorders.
PMID- 25114711
TI - Three-graded stratification of carbohydrate restriction by level of baseline
hemoglobin A1c for type 2 diabetes patients with a moderate low-carbohydrate
diet.
AB - BACKGROUND: A moderate low-carbohydrate diet has been receiving attention in the
dietary management of type 2 diabetes (T2DM). A fundamental issue has still to be
addressed; how much carbohydrate delta-reduction (Deltacarbohydrate) from
baseline would be necessary to achieve a certain decrease in hemoglobin A1c
(HbA1c) levels. OBJECTIVE: We investigated the effects of three-graded
stratification of carbohydrate restriction by patient baseline HbA1c levels on
glycemic control and effects of Deltacarbohydrate on decreases in HbA1c levels
(DeltaHbA1c) in each group. RESEARCH DESIGN AND METHODS: We treated 122
outpatients with T2DM by three-graded carbohydrate restriction according to
baseline HbA1c levels (<= 7.4% for Group 1, 7.5%-8.9% for Group 2 and >= 9.0% for
Group 3) and assessed their HbA1c levels, doses of anti-diabetic drugs and
macronutrient intakes over 6 months. RESULTS: At baseline, the mean HbA1c level
and carbohydrate intake were 6.9 +/- 0.4% and 252 +/- 59 g/day for Group 1 (n =
55), 8.1 +/- 0.4% and 282 +/- 85 g/day for Group 2 (n = 41) and 10.6 +/- 1.4% and
309 +/- 88 g/day for Group 3 (n = 26). Following three-graded carbohydrate
restriction for 6 months significantly decreased mean carbohydrate intake (g/day)
and HbA1c levels for all patients, from 274 +/- 78 to 168 +/- 52 g and from 8.1
+/- 1.6 to 7.1 +/- 0.9% (n = 122, P < 0.001 for both) and anti-diabetic drugs
could be tapered. DeltaHbA1c and Deltacarbohydrate were -0.4 +/- 0.4% and -74 +/-
69 g/day for Group 1, -0.6 +/- 0.9% and -117 +/- 78 g/day for Group 2 and -3.1 +/
1.4% and -156 +/- 74 g/day for Group 3. Linear regression analysis showed that
the greater the carbohydrate intake, the greater the HbA1c levels at baseline (P
= 0.001). Also, the greater the reduction in carbohydrate intake (g/day), the
greater the decrease in HbA1c levels (P < 0.001), but DeltaHbA1c was not
significantly influenced by changes in other macronutrient intakes (g/day).
CONCLUSIONS: Three-graded stratification of carbohydrate restriction according to
baseline HbA1c levels may provide T2DM patients with optimal objectives for
carbohydrate restriction and prevent restriction from being unnecessarily strict.
PMID- 25114712
TI - A novel cost effective and high-throughput isolation and identification method
for marine microalgae.
AB - BACKGROUND: Marine microalgae are of major ecologic and emerging economic
importance. Biotechnological screening schemes of microalgae for specific traits
and laboratory experiments to advance our knowledge on algal biology and
evolution strongly benefit from culture collections reflecting a maximum of the
natural inter- and intraspecific diversity. However, standard procedures for
strain isolation and identification, namely DNA extraction, purification,
amplification, sequencing and taxonomic identification still include considerable
constraints increasing the time required to establish new cultures. RESULTS: In
this study, we report a cost effective and high-throughput isolation and
identification method for marine microalgae. The throughput was increased by
applying strain isolation on plates and taxonomic identification by direct PCR
(dPCR) of phylogenetic marker genes in combination with a novel sequencing
electropherogram based screening method to assess the taxonomic diversity and
identity of the isolated cultures. For validation of the effectiveness of this
approach, we isolated and identified a range of unialgal cultures from natural
phytoplankton communities sampled in the Arctic Ocean. These cultures include the
isolate of a novel marine Chlorophyceae strain among several different diatoms.
CONCLUSIONS: We provide an efficient and effective approach leading from natural
phytoplankton communities to isolated and taxonomically identified algal strains
in only a few weeks. Validated with sensitive Arctic phytoplankton, this approach
overcomes the constraints of standard molecular characterisation and
establishment of unialgal cultures.
PMID- 25114713
TI - Predicting tooth surface loss using genetic algorithms-optimized artificial
neural networks.
AB - Our aim was to predict tooth surface loss in individuals without the need to
conduct clinical examinations. Artificial neural networks (ANNs) were used to
construct a mathematical model. Input data consisted of age, smoker status, type
of tooth brush, brushing, and consumption of pickled food, fizzy drinks, orange,
apple, lemon, and dried seeds. Output data were the sum of tooth surface loss
scores for selected teeth. The optimized constructed ANN consisted of 2-layer
network with 15 neurons in the first layer and one neuron in the second layer.
The data of 46 subjects were used to build the model, while the data of 15
subjects were used to test the model. Accepting an error of +/-5 scores for all
chosen teeth, the accuracy of the network becomes more than 80%. In conclusion,
this study shows that modeling tooth surface loss using ANNs is possible and can
be achieved with a high degree of accuracy.
PMID- 25114714
TI - RNA-RNA interaction prediction using genetic algorithm.
AB - BACKGROUND: RNA-RNA interaction plays an important role in the regulation of gene
expression and cell development. In this process, an RNA molecule prohibits the
translation of another RNA molecule by establishing stable interactions with it.
In the RNA-RNA interaction prediction problem, two RNA sequences are given as
inputs and the goal is to find the optimal secondary structure of two RNAs and
between them. Some different algorithms have been proposed to predict RNA-RNA
interaction structure. However, most of them suffer from high computational time.
RESULTS: In this paper, we introduce a novel genetic algorithm called GRNAs to
predict the RNA-RNA interaction. The proposed algorithm is performed on some
standard datasets with appropriate accuracy and lower time complexity in
comparison to the other state-of-the-art algorithms. In the proposed algorithm,
each individual is a secondary structure of two interacting RNAs. The minimum
free energy is considered as a fitness function for each individual. In each
generation, the algorithm is converged to find the optimal secondary structure
(minimum free energy structure) of two interacting RNAs by using crossover and
mutation operations. CONCLUSIONS: This algorithm is properly employed for joint
secondary structure prediction. The results achieved on a set of known
interacting RNA pairs are compared with the other related algorithms and the
effectiveness and validity of the proposed algorithm have been demonstrated. It
has been shown that time complexity of the algorithm in each iteration is as
efficient as the other approaches.
PMID- 25114716
TI - How can a change in the operating system of the mental health review board
promote the discharge of long-term hospitalized psychiatric patients? A case
study of Seoul city.
AB - BACKGROUND: One of the most typical and chronic problem in Korean mental health
system is the prolonged length of hospital stay. In contrast to there are many
components which leads to long length of stay of psychiatric patients in Korean
situation such as low and fixed medical fee for psychiatric inpatient treatment,
shortage of community resources, lack of care-givers' awareness and so on, there
are just few mechanisms to handle this issue such as Mental Health Review Board
(MHRB) which is based on Mental Health Act since 1995. However, the discharge
order rate was very low and there community care system after discharge order is
still very weak. CASE DESCRIPTION: The Korean government has revised the Mental
Health Act in 2008 and changed the operating principals of the MHRB from a
regional level to a local level to strengthen the function of MHRB. However, the
discharge order rate versus the whole evaluation requests still remains at a very
low level or less than 5%. And it is still very difficult to execute a discharge
order against a patient whose symptoms and conditions become psychiatrically
stabilized enough for discharge, due to a shortage of community care facilities
and a lack of social support system. These results are exactly same with former
studies. DISCUSSION: Any policies to promote psychiatric discharge including MHRB
are needed to take the comprehensive factors into consideration, such as payment
program, community infrastructure, increasing care-givers' acceptance and so on.
CONCLUSION: Despite of the political trial of Korean government to reduce length
of stay of chronic psychiatric patients, it was not successful. Still it had
failed to propose a detailed policy measure in terms of the above-mentioned
prerequisites. Therefore, new system and program developments including reform of
payment system which reflect prior studies' recommendations are essential.
PMID- 25114717
TI - Clinical and epidemiological profile of cases of deaths from stomach cancer in
the National Cancer Institute, Brazil.
AB - INTRODUCTION: Stomach cancer is the third most common cause of death worldwide,
mainly affecting people with low socioeconomic status. In Brazil, we expect
20,390 new cases of stomach cancer in 2014, in both sexes, and according to the
proportional distribution of the ten most prevalent types of cancer (except non
melanoma skin cancer) expected for 2014, this type of cancer was estimated to be
the fourth most common in men and sixth in women. AIM: To investigate and analyse
the clinical and epidemiological profile of deaths caused by stomach
adenocarcinoma in patients enrolled in the National Cancer Institute, Brazil.
METHODS: Cross-sectional study, with samples which consisted of data from the
medical records of deaths from stomach cancer, enrolled in the period from 1
February 2009 to 31 March 2012 and who had died as of 30 April 2012. STATISTICAL
ANALYSIS USED: The Epi Info (r), version 7. RESULTS: We included 264 cases,
mostly male. The mean age was 61.7 years. They were smokers, drinkers, white, and
married, with elementary education and an income of one minimum salary. They had
advanced stage disease (E IV), with symptoms characteristic of this phase, and
the majority died within six months. CONCLUSION: The findings are similar to
other studies. The advanced stage of the disease at the time of admission of the
patients reflects the difficulty for users of the Unified Health System to access
early diagnosis, demonstrating the need for efforts to identify groups and risk
factors for the development of gastric cancer. Training of health professionals
will facilitate planning and implementation of programmes for the prevention and
control of disease, considering socioeconomic conditions, as seen in the sample,
which is common among most users.
PMID- 25114718
TI - Sympathetic nervous system alterations with HER2+ antagonism: an early marker of
cardiac dysfunction with breast cancer treatment?
AB - BACKGROUND: HER2 antagonists (anti-HER2; e.g., trastuzumab and lapatinib) are
effective in treating an aggressive form of breast cancer (BC), but can cause
cardiotoxicity due to the disruption in neuregulin (NRG)/HER2+ ligand receptor
signalling. The recent data show that NRG-HER2 receptors located in the medulla
oblongata are important regulators of vasomotor tone. Disrupting the NRG-HER2
signalling in mouse medulla results in increased sympathetic nerve output and
blood pressure. We hypothesized that anti-HER2 agents would cause increased
sympathetic tone with changes in plasma catecholamines and NRG. METHODS: In 15
newly diagnosed HER2+ BC patients receiving anti-HER2 agents, vital signs were
measured along with supine plasma epinephrine (EPI), norepinephrine (NE), and NRG
at baseline and three months. Serial echocardiography was performed. RESULTS:
With three months of anti-HER2 treatment, NE increased (2.334 +/- 1.294 nmol/L
vs. 3.262 +/- 2.103 nmol/L; p = 0.004) and NRG decreased (12.7+/-15.7 ng/ml vs.
10.9 +/- 13.3 ng/ml; p = 0.036) with a corresponding increase in systolic blood
pressure (110 +/- 10 mmHg vs. 120 +/- 16 mmHg, p = 0.049) and diastolic blood
pressure (67 +/- 14 vs. 77 +/- 10, p = 0.009). There was no change, however, in
EPI (0.183 +/- 0.151 nmol/L vs. 0.159 +/- 0.174 nmol/L; p = 0.519) or heart rate
(73 +/- 12 bpm vs. 77 +/- 10 bpm, p = 0.146). Left ventricular ejection function
declined over the follow-up period (baseline 63 +/- 6% vs. follow-up 56 +/- 5%).
CONCLUSIONS: Anti-HER2 treatment results in increased NE, blood pressure, and
decreased NRG; this suggests that the inhibition of NRGHER2 signalling leads to
increased sympathoneural tone. Larger studies are needed to determine if these
observations have prognostic value and may be offset with medical interventions,
such as beta-blockers. CLINICAL TRIAL REGISTRATION: The study was registered with
www.clinicaltrials.gov (NCT00875238).
PMID- 25114715
TI - Diagnosis and treatment of perforated or bleeding peptic ulcers: 2013 WSES
position paper.
PMID- 25114719
TI - Spindle cell carcinoma of the tongue: a rare variant of squamous cell carcinoma.
AB - Spindle cell carcinoma (SpCC), a rare, aggressive variant of squamous cell
carcinoma (SCC), is characterised by proliferation of epithelial and mesenchymal
components. It is important to diagnose this variant of SCC, because of its
tendency to recur and early metastasis. It accounts for 1% of all tumours in the
oral cavity. In this paper, we have reported a case of SpCC of the tongue in a 65
year-old male who presented with a polypoidal growth over the lateral border of
his tongue with a short history of one month. Immunohistochemical expression of
cytokeratin was strongly positive in the epithelial component and focally in the
spindle cell component. The spindle cell component showed a strong positivity for
vimentin.
PMID- 25114720
TI - Clinicopathologic subtypes and compromise of lymph nodes in patients with breast
cancer.
AB - Breast cancer (BC) is currently a heterogeneous disease with variations in
clinical behaviour. Classification according to subtypes has allowed progress in
the individualisation of treatment. The objective of this study is to evaluate
the risk of axillary node compromise in patients with BC, according to
clinicopathologic subtypes. Materials and methods are a retrospective,
descriptive-analytical study. All patients that had undergone surgery for
invasive BC were included, with the study of sentinel lymph nodes (SLNs) at
Hospital Clinico de la Pontificia Universidad Catolica, between May 1999 and
December 2012. The results showed 632 patients fulfilled the inclusion criteria,
with the median age being 55 years (range: 28-95), and 559 (88.4%) patients
presented with estrogen receptor and/or progesterone receptor positive tumours.
Luminal A: 246 patients (38.9%), luminal B: 243 (38.4%), luminal not otherwise
specified: 70 (11.1%) triple negative (TN): 60 (9.5%) and over expression of
epidermal growth factor type 2 receptor (HER2 positive): 13 (2.1%). Luminal
tumours displayed a greater risk of metastasis in the SLNs, but this difference
was not statistically significant (p = 0.67). TN and HER2 positive tumours
presented the greatest proportion of metastatic compromise in non-sentinel lymph
nodes (non-SLNs) (57.1% and 50%, respectively). The presence of macrometastasis
(MAM) in the SLN was associated with a greater risk of compromise of the non-SLN.
CONCLUSIONS: Luminal tumours are the most frequent and present a greater
proportion of axillary lymph node compromise, without being statistically
significant. TN and HER2 positive tumours tend to have a higher axillary
compromise; however, this was not statistically significant in either. Only the
presence of MAM in SLNs displayed a statistically significantly association in
the compromise of non-SLNs.
PMID- 25114721
TI - Anaplastic thyroid cancer: multimodal treatment results.
AB - BACKGROUND: Anaplastic thyroid cancer is a rare and lethal disease. It accounts
for 1-2% of thyroid malignancies, but specific mortality is higher than 90%. It
is an aggressive locoregional disease with a high metastatic capacity. There is
no agreement with regards to the best treatment. We analysed the results of
treatment in a mestizo population treated in the National Cancer Institute
(Mexico). METHODS: We reviewed 1,581 files of thyroid carcinomas; of these, 29
(1.83%) had anaplastic thyroid carcinoma. Demographic variables, clinical
manifestations, tumour characteristics, and treatments were analysed. RESULTS:
The median age was 64.5 +/- 13.2 years. Females were more affected (female/male
ratio: 2.6:1); 21 cases occurred in women (72.4%), and eight in males (27.6%).
The most common manifestations were neck enlargement (93.10%) and hoarseness
(71.31%). The median tumour size was 8 cm (range: 4-20 cm). The percentage of
cases which presented in clinical stage IVA was 10.3%, with 62.1% presenting in
clinical stage IVb and 27.6% presenting in clinical stage VIc. Complete resection
(R0) (p = 0.05), radiation doses of higher than 33.1 Gy (p = 0.04), and
multimodal therapy were associated with better survival. Surgery plus
radiotherapy with or without systemic treatment (p = 0.006). The median overall
survival was 119 days (IC 95%, 36.3-201.6). Six-month, one-year and two-year
survival was 37.9%, 21% and 13%, respectively. CONCLUSION: Complete surgical
resection is associated with better survival but is very difficult to achieve due
to aggressive biological behaviour. Multimodal therapy is associated with better
survival and a better quality of life. There is a need for more effective
systemic treatments as extensive surgical resections have little overall benefit
in highly invasive and metastatic disease.
PMID- 25114723
TI - NHS reforms in England: the implications for chemotherapy commissioning.
AB - For oncology, one of the biggest effects of the reforms to the National Health
Service (NHS) in England has been the designation of systemic anticancer
treatments (other than hormonal agents) as a specialised service. This means that
all decisions regarding the commissioning of chemotherapy are made at the
national level via NHS England (NHSE), under expert guidance from the
Chemotherapy Clinical Reference Group (CRG). Commissioning decisions will be
based on several factors, not only clinical efficacy and cost/affordability, but
also the 'added value' that a new treatment may offer in terms of patient
outcomes, resource utilisation, and/or wider benefits to society. Oncology health
care professionals (HCPs) are in a position to affect cancer commissioning
decisions in the reformed NHS, not only the small number who are members of the
Chemotherapy CRG, but also as advisors to the Chemotherapy CRG via disease
specific consensus work, and through participation in the collection and
reporting of real-life data on patient outcomes. With the emerging emphasis on
both consensus work and outcomes data, a step change can also be expected in the
relationship between HCPs and the pharmaceutical industry, including a
strengthened role for non-promotional education, support for forums and consensus
groups, and facilitation of the development, collection, and dissemination of
findings from real-life practice. In addition, there will be an onus on the
pharmaceutical industry to provide information on the implications that new
products may have for service delivery and capacity and for meeting patients' and
society's expectations. This information will need to be developed and delivered
in a timely way, well in advance of the launch of a new product.
PMID- 25114724
TI - Watching as an ordinary affect: Care and mothers' preemption of injury in child
supervision.
AB - As unintentional injuries continue to be the leading cause of hospitalization and
death for toddlers between the ages of 1 and 4, the Centers for Disease Control
has argued that child supervision is a key factor in reducing these injuries and
fatalities. This article focuses on the affective relationships in the concept of
supervision and practice of watching as an injury prevention method. Three parts
frame our argument. First, we describe how watching is an ordinary affect.
Second, as part of the ethos of caring, watching is embedded in a temporal frame
of anticipation and gives rise to an affectsphere of watching and to a parents'
subjectivity as 'good' or 'bad' supervisors. Third, these affective relationships
generate seemingly contradictory outcomes wherein children are expected to gain
independence and experience injury. The affective qualities of watching provide a
critique of the individualizing forces of supervision and an analysis of
subjectivities generated by gender and class.
PMID- 25114722
TI - Neuroendocrine carcinoma of the cervix presenting as intractable hyponatremic
seizures due to paraneoplastic SIADH-a rare case report and brief review of the
literature.
AB - Herein is presented an interesting case of small-cell neuroendocrine carcinoma of
the cervix which initially manifests as seizures due to hyponatremia caused by
paraneoplastic syndrome of inappropriate anti diuretic hormone (SIADH). Awareness
of a paraneoplastic syndrome at presentation can lead to early diagnosis and
early initiation of treatment. The management is also unique in that it combines
treating the paraneoplastic aspects as well as targeting the tumour itself.
Multimodality treatment gives the best outcome in this aggressive tumour.
PMID- 25114725
TI - Use of diagnostic imaging in the evaluation of gastrointestinal tract
duplications.
AB - BACKGROUND: Gastrointestinal tract duplication is a rare malformation associated
with the presence of additional segment of the fetal gut. The aim of this study
was to retrospectively review clinical features and imaging findings in
intraoperatively confirmed cases of gastrointestinal tract duplication in
children. MATERIAL/METHODS: The analysis included own material from the years
2002-2012. The analyzed group included 14 children, among them 8 boys and 6
girls. The youngest patient was diagnosed at the age of three weeks, and the
oldest at 12 years of age. RESULTS: The duplication cysts were identified in the
esophagus (n=2), stomach (n=5), duodenum (n=1), terminal ileum (n=5), and rectum
(n=1). In four cases, the duplication coexisted with other anomalies, such as
patent urachus, Meckel's diverticulum, mesenteric cyst, and accessory pancreas.
Clinical manifestation of gastrointestinal duplication cysts was variable, and
some of them were detected accidently. Thin- or thick-walled cystic structures
adjacent to the wall of neighboring gastrointestinal segment were documented on
diagnostic imaging. CONCLUSIONS: Ultrasound and computed tomography are the
methods of choice in the evaluation of gastrointestinal duplication cysts. Apart
from the diagnosis of the duplication cyst, an important issue is the detection
of concomitant developmental pathologies, including pancreatic heterotopy.
PMID- 25114726
TI - Effect of a short time concentric versus eccentric training program on
electromyography activity and peak torque of quadriceps.
AB - The purpose of this study was to examine the effect of an 8-week concentric (CON)
versus eccentric (ECC) isokinetic training program on the electromyography (EMG)
signal amplitude of vastus medialis (VM), vastus lateralis (VL) and rectus
femoris (RF). Also, the isometric (ISO) and dynamic maximum strength of the knee
extensors were assessed. Eighteen physically healthy male subjects (age 22 +/- 1
years, body height 177 +/- 4 cm, body mass 73 +/- 7 kg) performed four weeks of
unilateral CON isokinetic training for the quadriceps of the dominant leg on a
REV9000 dynamometer. At the end of the fourth week, the sample was divided into
two groups, with one group performing additional four weeks of unilateral ECC
training and the other continuing with CON training. The training sessions
consisted of three sets of ten maximal repetitions at a velocity of 60os-1, three
days per week for eight weeks. The results showed that CON and ECC groups
improved the peak torque in all types of contractions. Also, both groups
presented increases in the avgEMG for VL, VM and RF. The present investigation
showed that CON training elicited increases of the ISO peak torque and VM avgEMG
in the CON contraction. Additionally, significant gains were reported after the
ECC training on the VM avgEMG in all contractions and RM avgEMG in CON
contraction.
PMID- 25114727
TI - Lower Extremity Muscle Activity During a Women's Overhand Lacrosse Shot.
AB - The purpose of this study was to describe lower extremity muscle activity during
the lacrosse shot. Participants (n=5 females, age 22+/-2 years, body height
162.6+/-15.2 cm, body mass 63.7+/-23.6 kg) were free from injury and had at least
one year of lacrosse experience. The lead leg was instrumented with
electromyography (EMG) leads to measure muscle activity of the rectus femoris
(RF), biceps femoris (BF), tibialis anterior (TA), and medial gastrocnemius (GA).
Participants completed five trials of a warm-up speed shot (Slow) and a game
speed shot (Fast). Video analysis was used to identify the discrete events
defining specific movement phases. Full-wave rectified data were averaged per
muscle per phase (Crank Back Minor, Crank Back Major, Stick Acceleration, Stick
Deceleration). Average EMG per muscle was analyzed using a 4 (Phase) * 2 (Speed)
ANOVA. BF was greater during Fast vs. Slow for all phases (p<0.05), while TA was
not influenced by either Phase or Speed (p>0.05). RF and GA were each influenced
by the interaction of Phase and Speed (p<0.05) with GA being greater during Fast
vs. Slow shots during all phases and RF greater during Crank Back Minor and Major
as well as Stick Deceleration (p<0.05) but only tended to be greater during Stick
Acceleration (p=0.076) for Fast vs. Slow. The greater muscle activity (BF, RF,
GA) during Fast vs. Slow shots may have been related to a faster approach speed
and/or need to create a stiff lower extremity to allow for faster upper extremity
movements.
PMID- 25114728
TI - Neuromuscular responses of elite skaters during different roller figure skating
jumps.
AB - This study aimed to describe the neuromuscular activity of elite athletes who
performed various roller figure skating jumps, to determine whether the muscle
activation is greater during jumps with more rotations and in which phase the
muscles are more active. This study also aimed to analyze if there is any
difference in the muscle activity pattern between female and male skaters. Four
elite skaters were evaluated, and each participated in two experimental sessions.
During the first session, anthropometric data were collected, and the consent
forms were signed. For the second session, neuromuscular data were collected
during jumps, which were performed with skates at a rink. The following four
roller figure skating jumps were evaluated: single Axel, double Axel, double
Mapes and triple Mapes. The neuromuscular activity of the following seven muscles
was obtained with an electromyograph which was fixed to the waist of each skater
with a strap: biceps femoris, lateral gastrocnemius, tibialis anterior, rectus
femoris, vastus lateralis, vastus medialis and gluteus maximus. The signal was
transmitted wirelessly to a laptop. During the roller figure skating jumps, the
lateral gastrocnemius, rectus femoris, vastus lateralis, biceps femoris and
gluteus maximus, showed more activation during the jumps with more rotations, and
the activation mainly occurred during the propulsion and flight phases. Female
skaters demonstrated higher muscle activities in tibialis anterior, vastus
lateralis, vastus medialis and gluteus maximus during the landing phase of the
triple Mapes, when compared to their male counterparts. The results obtained in
this study should be considered when planning training programs with specific
exercises that closely resemble the roller figure skating jumps. This may be
important for the success of elite skaters in competitions.
PMID- 25114729
TI - Comparison of static balance and the role of vision in elite athletes.
AB - When prescribing balance exercises to athletes in different sports, it may be
important to recognize performance variations. Indeed, how athletes from
different sports perform on balance tests is not well understood. The goal of the
present study was to compare static balance and the role of vision among elite
sprinters, jumpers and rugby players. The modified clinical test of sensory
interaction on balance (mCTSIB) was used to assess the velocity of the center-of
pressure (CoP) on a force platform during a 30 s bipedal quiet standing posture
in 4 conditions: firm surface with opened and closed eyes, foam surface with
opened and closed eyes. Three-factor ANOVA indicated a significant main effect
for groups (F=21.69, df=2, p<0.001, eta(2) = 0.34). Significant main effect of
vision (F=43.20, df=1, p<0.001, eta(2) = 0.34) and surface (F=193.41, df=1,
p<0.001, eta(2) = 0.70) as well as an interaction between vision (eyes open, eyes
closed) and surface (firm and foam) (F=21.79, df=1, p=0.001) were reported in all
groups. The subsequent Bonferroni-Dunn post hoc test indicated that rugby players
displayed better static balance than sprinters and jumpers (p=0.001). The
comparison of sprinters and jumpers did not reveal significant differences
(p>0.05). The nature of the sport practiced and the absence of visual control are
linked to modify static balance in elite athletes. Coaches and strength and
conditioning professionals are recommended to use a variety of exercises to
improve balance, including both exercises with opened and closed eyes on
progressively challenging surfaces in order to make decisions about tasks and
sensory availability during assessment and training.
PMID- 25114730
TI - Effect of training mode on post-exercise heart rate recovery of trained cyclists.
AB - The sympathetic nervous system dominates the regulation of body functions during
exercise. Therefore after exercise, the sympathetic nervous system withdraws and
the parasympathetic nervous system helps the body return to a resting state. In
the examination of this relationship, the purpose of this study was to compare
recovery heart rates (HR) of anaerobically versus aerobically trained cyclists.
With all values given as means +/- SD, anaerobically trained track cyclists
(n=10, age=25.9 +/- 6.0 yrs, body mass=82.7 +/- 7.1 kg, body fat=10.0 +/- 6.3%)
and aerobically trained road cyclists (n=15, age=39.9 +/- 8.5 yrs, body mass=75.3
+/- 9.9 kg, body fat=13.1 +/- 4.5%) underwent a maximal oxygen uptake test. Heart
rate recovery was examined on a relative basis using heart rate reserve as well
as the absolute difference between maximum HR and each of two recovery HRs. The
post-exercise change in HR at minute one for the track cyclists and road cyclists
respectively were 22 +/- 8 bpm and 25 +/- 12 bpm. At minute two, the mean drop
for track cyclists was significantly (p<0.05) greater than the road cyclists (52
+/- 15 bpm and 64 +/- 11 bpm). Training mode showed statistically significant
effects on the speed of heart rate recovery in trained cyclists. Greater
variability in recovery heart rate at minute two versus minute one suggests that
the heart rate should be monitored longer than one minute of recovery for a
better analysis of post-exercise autonomic shift.
PMID- 25114731
TI - The kinematic control during the backward gait and knee proprioception: insights
from lesions of the anterior cruciate ligament.
AB - An already existing large volume of work on kinematics documents a reduction of
step length during unusual gaits, such as backward walking. This is mainly
explained in terms of modifications of some biomechanical properties. In the
present study, we propose that the proprioceptive information from the knee may
be involved in this change of motor strategy. Specifically, we show that a non
automated condition such as backward walking can elicit different motor
strategies in subjects with reduced proprioceptive feedback after anterior
cruciate ligament lesion (ACL). For this purpose, the kinematic parameters during
forward and backward walking in subjects with ACL deficit were compared to two
control groups: a group with intact ACL and a group with surgically reconstructed
ACL. The knee proprioception was tested measuring the threshold for detection of
passive knee motion. Subjects were asked to walk on a level treadmill at five
different velocities (1-5km/h) in forward and backward direction, thereby
calculating the cadence and step length. Results showed that forward walking
parameters were largely unaffected in subjects with ACL damage. However, they
failed to reduce step length during backward walking, a correction that was
normally observed in all control subjects and in subjects with normal
proprioceptive feedback after ACL reconstruction. The main result of the present
study is that knee proprioception is an important signal used by the brain to
reduce step length during the backward gait. This can have a significant impact
on clinical evaluation and rehabilitation.
PMID- 25114732
TI - Effectiveness of Selected Fitness Exercises on Stress of Femoral Neck using
Musculoskeletal Dynamics Simulations and Finite Element Model.
AB - The purpose of the study was to establish a dynamics model and a three
dimensional (3D) finite element model to analyze loading characteristics of
femoral neck during walking, squat, single-leg standing, and forward and lateral
lunges. One male volunteer performed three trials of the five movements. The 3D
kinematic data were captured and imported into the LifeMOD to establish a
musculoskeletal dynamics model to obtain joint reaction and muscle forces of
iliacus, gluteus medius, gluteus maximus, psoas major and adductor magnus. The
loading data LfeMOD were imported and transformed into a hip finite-element
model. The results of the finite element femur model showed that stress was
localized along the compression arc and the tension arc. In addition, the
trabecular bone and tension lines of the Ward's triangle also demonstrated high
stress. The compact bone received the greatest peak stress in the forward lunge
and the least stress in the squat. However, the spongy bone in the femoral neck
region had the greatest stress during the walk and the least stress in the squat.
The results from this study indicate that the forward lunge may be an effective
method to prevent femoral neck fractures. Walking is another effective and simple
method that may improve bone mass of the Ward's triangle and prevent osteoporosis
and femoral neck fracture.
PMID- 25114733
TI - Effects of regular physical exercises in the water on the metabolic profile of
women with abdominal obesity.
AB - Recreational physical exercise in the water is predominantly based on aerobic
metabolism. Since it involves both carbohydrate and lipid sources of energy, aqua
aerobics has a beneficial effect on metabolism of these substrates. The aim of
the study was to assess the impact of a 3 month aqua aerobics training program on
the metabolic profile of women with abdominal obesity. The study sample comprised
32 women aged 41-72 years. Somatic characteristics and variables characterizing
carbohydrate and lipid metabolism were measured before the commencement and after
the completion of the training program. During the 2nd measurement all mean
anthropometric variables were found to be significantly lower (p<=0.01). In the
blood lipid profile, the concentrations of total cholesterol, LDL-cholesterol and
HOMAIR were significantly lower (p<0.01). Furthermore, the levels of fasting
triglycerides, glucose and insulin were reduced significantly (p<=0.05) after the
training program. The aqua aerobics program contributed to positive changes in
lipid metabolism, anthropometric variables, as well as the fasting insulin,
glucose levels and insulin resistance index in women with abdominal obesity.
PMID- 25114734
TI - Multi-Stage 20-m Shuttle Run Fitness Test, Maximal Oxygen Uptake and Velocity at
Maximal Oxygen Uptake.
AB - The multi-stage 20-m shuttle run fitness test (20mMSFT) is a popular field test
which is widely used to measure aerobic fitness by predicting maximum oxygen
uptake (VO2max) and performance. However, the velocity at which VO2max occurs
(vVO2max) is a better indicator of performance than VO2max, and can be used to
explain inter-individual differences in performance that VO2max cannot. It has
been reported as a better predictor for running performance and it can be used to
monitor athletes' training for predicting optimal training intensity. This study
investigated the validity and suitability of predicting VO2max and vVO2max of
adult subjects on the basis of the performance of the 20mMST. Forty eight (25
male and 23 female) physical education students performed, in random order, a
laboratory based continuous horizontal treadmill test to determine VO2max,
vVO2max and a 20mMST, with an interval of 3 days between each test. The results
revealed significant correlations between the number of shuttles in the 20mMSFT
and directly determined VO2max (r = 0.87, p<0.05) and vVO2max (r = 0.93, p<0.05).
The equation for prediction of VO2max was y = 0.0276x + 27.504, whereas for
vVO2max it was y = 0.0937x + 6.890. It can be concluded that the 20mMSFT can
accurately predict VO2max and vVO2max and this field test can provide useful
information regarding aerobic fitness of adults. The predicted vVO2max can be
used in monitoring athletes, especially in determining optimal training
intensity.
PMID- 25114735
TI - The effect of a single session of whole-body vibration training in recreationally
active men on the excitability of the central and peripheral nervous system.
AB - Vibration training has become a popular method used in professional sports and
recreation. In this study, we examined the effect of whole-body vibration
training on the central nervous system and muscle excitability in a group of 28
active men. Subjects were assigned randomly to one of two experimental groups
with different variables of vibrations. The chronaximetry method was used to
evaluate the effect of a single session of whole-body vibration training on the
excitability of the rectus femoris and brachioradialis muscles. The examination
of the fusing and flickering frequencies of the light stimulus was performed. An
increase in the excitability of the quadriceps femoris muscle due to low
intensity vibrations (20 Hz frequency, 2 mm amplitude) was noted, and a return to
the initial values was observed 30 min after the application of vibration. High
intensity vibrations (60 Hz frequency, 4 mm amplitude) caused elongations of the
chronaxy time; however, these differences were not statistically significant.
Neither a low intensity vibration amplitude of 2 mm (frequency of 20 Hz) nor a
high intensity vibration amplitude of 4 mm (frequency of 60 Hz) caused a change
in the excitability of the central nervous system, as revealed by the average
frequency of the fusing and flickering of the light stimulus. A single session of
high intensity whole-body vibration did not significantly decrease the
excitability of the peripheral nervous system while the central nervous system
did not seem to be affected.
PMID- 25114736
TI - Insights into Supplements with Tribulus Terrestris used by Athletes.
AB - Herbal and nutritional supplements are more and more popular in the western
population. One of them is an extract of an exotic plant, named Tribulus
terrestris (TT). TT is a component of several supplements that are available over
the-counter and widely recommended, generally as enhancers of human vitality. TT
is touted as a testosterone booster and remedy for impaired erectile function;
therefore, it is targeted at physically active men, including male athletes.
Based on the scientific literature describing the results of clinical trials,
this review attempted to verify information on marketing TT with particular
reference to the needs of athletes. It was found that there are few reliable data
on the usefulness of TT in competitive sport. In humans, a TT extract used alone
without additional components does not improve androgenic status or physical
performance among athletes. The results of a few studies have showed that the
combination of TT with other pharmacological components increases testosterone
levels, but it was not discovered which components of the mixture contributed to
that effect. TT contains several organic compounds including alkaloids and
steroidal glycosides, of which pharmacological action in humans is not completely
explained. One anti-doping study reported an incident with a TT supplement
contaminated by a banned steroid. Toxicological studies regarding TT have been
carried out on animals only, however, one accidental poisoning of a man was
described. The Australian Institute of Sport does not recommend athletes' usage
of TT. So far, the published data concerning TT do not provide strong evidence
for either usefulness or safe usage in sport.
PMID- 25114737
TI - Changes in urinary 8-hydroxydeoxyguanosine levels during heptathlon race in
professional female athletes.
AB - Acute strenuous exercise can induce a state of oxidative stress affecting the
involved muscles. Heptathlon is a multi-event exercise of two days duration and
can be considered an acute, intensive endurance exercise. The purpose of this
study is to compare the oxidative stress response to heptathlon events day by day
and to determine the impact of this type of exercise on oxidative stress
biomarkers. The study subjects included eight heptathlon athletes who
participated in the National First Class Republic competition in Egypt (October
19-21, 2011). Blood samples were collected at rest after exercise for two
successive days and analyzed for malondialdehyde (MDA). Morning urine samples
were collected one hour after exercise for each day and were analyzed for 8
hydroxydeoxyguanosine (8-OHdG). Results revealed a significant increase (p<0.05)
in both plasma MDA and urine 8-OHdG levels after exercise regardless of the day.
We concluded that exercise generates higher MDA levels compared to DNA strand
breaks and oxidative DNA damage in athletes with antioxidant supplementation.
PMID- 25114738
TI - Effect of number of touches and exercise duration on the kinematic profile and
heart rate response during small-sided games in soccer.
AB - This study aimed to examine the effect of exercise duration and the number of
touches allowed during possession on time-motion characteristics and the
physiological responses of soccer players in 6 vs. 6 small-sided games (SSGs)
lasting 12 minutes. The analysis divided each game into two 6-min periods and we
compared two formats: free play (SSGFP) vs. a maximum of two touches per
individual possession (SSG2T). Participants were 12 semi-professional players
(age: 22.7+/-4.3 years; body height: 177.5+/-4.9 cm; body mass: 74.9+/-6.3 kg)
and the following variables were measured by means of heart rate monitors and GPS
devices: mean heart rate (HRmean), time spent in each exercise intensity zone,
total distance covered, total distance covered in different speed zones, number
of accelerations at different intensities, maximum speed reached, player load,
and the work-to-rest ratio. The results showed that in SSGFP there was a decrease
in the intensity of physical parameters during the second 6-min period (6-12
min), whereas this decrease was not observed when a maximum of two touches per
individual possession was allowed. During the second period (6-12 min) of SSG2T
there was an increase in HRmean and in the time spent in high exercise intensity
zones, but these differences were not observed in SSGFP. The value of these
findings for soccer coaches is that they illustrate how different technical,
tactical or conditioning objectives could be addressed by altering the length and
format of the SSG used in training.
PMID- 25114739
TI - Effects of Strength Training Combined with Specific Plyometric exercises on body
composition, vertical jump height and lower limb strength development in elite
male handball players: a case study.
AB - The purpose of the present study was to identify the effects of a strength
training program combined with specific plyometric exercises on body composition,
vertical jump (VJ) height and strength development of lower limbs in elite male
handball players. A 12-week program with combined strength and specific
plyometric exercises was carried out for 7 weeks. Twelve elite male handball
players (age: 21.6 +/- 1.73) competing in the Portuguese Major League
participated in the study. Besides the anthropometric measurements, several
standardized jump tests were applied to assess VJ performance together with the
strength development of the lower limbs in an isokinetic setting. No significant
changes were found in body circumferences and diameters. Body fat content and fat
mass decreased by 16.4 and 15.7% respectively, while lean body mass increased by
2.1%. Despite small significance, there was in fact an increase in squat jump
(SJ), counter movement jump (CMJ) and 40 consecutive jumps after the training
period (6.1, 3.8 and 6.8%, respectively). After the applied protocol, peak torque
increased in lower limb extension and flexion in the majority of the movements
assessed at 90os-1. Consequently, it is possible to conclude that combining
general strength-training with plyometric exercises can not only increase lower
limb strength and improve VJ performance but also reduce body fat content.
PMID- 25114740
TI - Prediction of rowing ergometer performance from functional anaerobic power,
strength and anthropometric components.
AB - The aim of this research was to develop different regression models to predict
2000 m rowing ergometer performance with the use of anthropometric, anaerobic and
strength variables and to determine how precisely the prediction models
constituted by different variables predict performance, when conducted together
in the same equation or individually. 38 male collegiate rowers (20.17 +/- 1.22
years) participated in this study. Anthropometric, strength, 2000 m maximal
rowing ergometer and rowing anaerobic power tests were applied. Multiple linear
regression procedures were employed in SPSS 16 to constitute five different
regression formulas using a different group of variables. The reliability of the
regression models was expressed by R2 and the standard error of estimate (SEE).
Relationships of all parameters with performance were investigated through
Pearson correlation coefficients. The prediction model using a combination of
anaerobic, strength and anthropometric variables was found to be the most
reliable equation to predict 2000 m rowing ergometer performance (R2 = 0.92, SEE=
3.11 s). Besides, the equation that used rowing anaerobic and strength test
results also provided a reliable prediction (R2 = 0.85, SEE= 4.27 s). As a
conclusion, it seems clear that physiological determinants which are affected by
anaerobic energy pathways should also get involved in the processes and models
used for performance prediction and talent identification in rowing.
PMID- 25114741
TI - The impact of immediate verbal feedback on the improvement of swimming technique.
AB - The present research attempts to ascertain the impact of immediate verbal
feedback (IVF) on modifications of stroke length (SL). In all swimming styles,
stroke length is considered an essential kinematic parameter of the swimming
cycle. It is important for swimming mechanics and energetics. If SL shortens
while the stroke rate (SR) remains unchanged or decreases, the temporal-spatial
structure of swimming is considered erroneous. It results in a lower swimming
velocity. Our research included 64 subjects, who were divided into two groups:
the experimental - E (n=32) and the control - C (n=32) groups. A pretest and a
post-test were conducted. The subjects swam the front crawl over the test
distance of 25m at Vmax. Only the E group subjects were provided with IVF aiming
to increase their SL. All tests were filmed by two cameras (50 samples*s-1). The
kinematic parameters of the swimming cycle were analyzed using the SIMI Reality
Motion Systems 2D software (SIMI Reality Motion Systems 2D GmbH, Germany). The
movement analysis allowed to determine the average horizontal swimming velocity
over 15 meters. The repeated measures analysis of variance ANOVA with a post-hoc
Tukey range test demonstrated statistically significant (p<0.05) differences
between the two groups in terms of SL and swimming velocity. IVF brought about a
6.93% (Simi method) and a 5.09% (Hay method) increase in SL, as well as a 2.92%
increase in swimming velocity.
PMID- 25114742
TI - Reliability of tethered swimming evaluation in age group swimmers.
AB - The aim of the present study was to examine the reliability of tethered swimming
in the evaluation of age group swimmers. The sample was composed of 8 male
national level swimmers with at least 4 years of experience in competitive
swimming. Each swimmer performed two 30 second maximal intensity tethered
swimming tests, on separate days. Individual force-time curves were registered to
assess maximum force, mean force and the mean impulse of force. Both consistency
and reliability were very strong, with Cronbach's Alpha values ranging from 0.970
to 0.995. All the applied metrics presented a very high agreement between tests,
with the mean impulse of force presenting the highest. These results indicate
that tethered swimming can be used to evaluate age group swimmers. Furthermore,
better comprehension of the swimmers ability to effectively exert force in the
water can be obtained using the impulse of force.
PMID- 25114744
TI - Game-Related Volleyball Skills that Influence Victory.
AB - The aim of the present study was to identify the volleyball skills that
discriminate in favour of victory. Twenty-four games (n=24) from the Senior Men's
Volleyball World Championship played in Italy in 2010 were chosen and analyzed
with Data Volley software. The discriminating function was used to identify the
discriminating variables, using a canonical structuring coefficient of |SC| >=
.30. The results suggest that service points, reception errors, and blocking
errors were the discriminating variables that identify the final outcome of the
match (victory/defeat). Moreover, successful service points were the major
variable most likely associated with match success (victory). In this sense,
increasing the effectiveness of service should be a top priority in coaching
elite volleyball teams.
PMID- 25114743
TI - Effects of high-intensity blood flow restriction exercise on muscle fatigue.
AB - Strength training combined with blood flow restriction (BFR) have been used to
improve the levels of muscle adaptation. The aim of this paper was to investigate
the acute effect of high intensity squats with and without blood flow restriction
on muscular fatigue levels. Twelve athletes (aged 25.95 +/- 0.84 years) were
randomized into two groups: without Blood Flow Restriction (NFR, n = 6) and With
Blood Flow Restriction (WFR, n = 6) that performed a series of free weight squats
with 80% 1-RM until concentric failure. The strength of the quadriceps extensors
was assessed in a maximum voluntary isometric contraction integrated to signals
from the surface electromyogram. The average frequency showed significant
reductions in the WFR group for the vastus lateralis and vastus medialis muscles,
and intergroup only for the vastus medialis. In conclusion, a set of squats at
high intensity with BFR could compromise muscle strength immediately after
exercise, however, differences were not significant between groups.
PMID- 25114745
TI - The reliability of a functional agility test for water polo.
AB - Few functional agility tests for water polo take into consideration its specific
characteristics. The preliminary objective of this study was to evaluate the
reliability of an agility test for water polo players. Fifteen players (16.3 +/-
1.8 years old) with a minimum of two years of competitive experience were
evaluated. A Functional Test for Agility Performance (FTAP) was designed to
represent the context of this sport. Several trials were performed to familiarize
the athlete with the movement. Two experienced coaches measured three repetitions
of the FTAP. Descriptive statistics, repeated measures analysis of variance
(ANOVA), 95% limit of agreement (LOA), intraclass correlation coefficient (ICC)
and standard error of measurements (SEM) were used for data analysis. It was
considered that certain criteria of reliability measures were met. There was no
significant difference between the repetitions, which may be explained by an
effect of the evaluator, the ability of the players or fatigue (p > 0.05). The
ICC average from evaluators was high (0.88). The SEM varied between 0.13 s and
0.49 s. The CV average considering each individual was near 6-7%. These values
depended on the condition of measurement. As the FTAP contains some
characteristics that create a degree of unpredictability, the same athlete may
reach different performance results, increasing variability. An adjustment in the
sample, familiarization and careful selection of subjects help to improve this
situation and enhance the reliability of the indicators.
PMID- 25114746
TI - Comparing Tactical Behaviour of Soccer Players in 3 vs. 3 and 6 vs. 6 Small-Sided
Games.
AB - The present study aimed to compare players' tactical behaviour in 3 vs. 3 and 6
vs. 6 soccer small-sided games (SSGs). The sample comprised 3,482 tactical
actions performed by 18 U-11 youth soccer players from a Portuguese club, in 3
vs. 3 and 6 vs. 6 SSGs. All participants played eight minutes in both situations
and field size was adapted according to the number of players involved (30 m *
19.5 m for 3 vs. 3 and 60 m * 39 m for 6 vs. 6). The System of Tactical
Assessment in Soccer (FUT-SAT) was used for data collection and analyses.
Descriptive analysis was conducted to verify frequencies and percentages of the
variables assessed. The chi-squared (chi(2)) test was performed to compare the
frequencies of the variables between 3 vs. 3 and 6 vs. 6 SSGs and Standardized
Residuals (e) were used to examine the influence of the frequency of one or more
variables within 3 vs. 3 and 6 vs. 6 SSGs. Data treatment was performed through
SPSS for Windows(r), version 18.0. Results indicated that players displayed safer
behaviours in 6 vs. 6 SSG and more aggressive behaviours in 3 vs. 3 SSG. Findings
can aid coaches and teachers to develop different players' tactical skills
according to the chosen SSG (3 vs. 3 or 6 vs. 6) form.
PMID- 25114747
TI - Effects of Match Location, Match Status and Quality of Opposition on Regaining
Possession in UEFA Champions League.
AB - The present study aimed to examine the independent and interactive effects of
match location, match status, and quality of opposition on regaining possession,
analysed by the type and zone of ball recovery, in matches played in the 2011
2012 UEFA Champions League. Twenty-eight matches of the knockout phase were
evaluated post-event using a computerized notational analysis system. Multinomial
logistic regression analysis was applied to identify the effects of the
previously mentioned situational variables on ball recovery type and zone. Match
status and quality of opposition main effects were observed for both dependent
variables, while main effects of match location were only evident for ball
recovery zone. Additionally, the interactions Match location (*) Quality of
opposition and Match status (*) Quality of opposition were significant for both
type and zone of ball recovery. Better teams employed more proactive defensive
strategies, since, even when winning, they tried to sustain their defensive
success on actions that aimed to gain the ball from the opponents. Results
emphasized the tendency for home and losing teams to defend in more advanced
pitch zones. Better-ranked teams were also more effective than worse-ranked teams
in applying defensive pressure in more advanced pitch positions. The findings of
the study suggest that the defensive strategies used by better teams imply more
intense and organized collective processes in order to recover the ball directly
from the opposing team. Furthermore, defending away from own goal and near the
opponent's one seems to be associated with success in elite soccer.
PMID- 25114748
TI - The examination of different tests for the evaluation of the efficiency of the
eggbeater kicks.
AB - The eggbeater kick presents an important basic technical skill in water polo. The
aim of this study was to examine some different tests in order to recommend the
best ones for the evaluation of the eggbeater kick. Twenty eight young male water
polo players performed one test (squat jump) on land and ten tests in water:
tethered swimming with legs only, using alternating and simultaneous eggbeater
kicks, jumps out of water from basic and vertical (arms vertically above the
head) position, water start and swimming two meters and swimming horizontally
with legs only five meters with a flying start. The differences between tests
were checked by executing dependent t-tests, while Pearson's correlation
coefficients were calculated to evaluate the correlation between different
parameters. Results showed that when performing alternate eggbeater kicks greater
average forces were produced by the water polo players when compared to
consecutive simultaneous eggbeater kicks. However, a short time maximal
acceleration of the body in the vertical and horizontal plane was greater when
the single simultaneous kick was performed. It was determined that horizontal
swimming using legs only and a squat jump were less useful for the evaluation of
the eggbeater kick. Therefore, the recommendation was to measure the average
force of successive alternating eggbeater kicks, the height of the jump out of
the water from the basic position and the water start and swim over a distance of
2 meters.
PMID- 25114749
TI - Isokinetic leg strength and power in elite handball players.
AB - Isokinetic strength evaluation of the knee flexion and extension in concentric
mode of contraction is an important part of the comprehensive evaluation of
athletes. The aims of this study were to evaluate the isokinetic knee peak torque
in both the extension and flexion movement in the dominant and non-dominant leg,
and the relationship with jumping performance. Twelve elite male handball players
from the top Spanish handball division voluntary participated in the study (age
27.68 +/- 4.12 years; body mass 92.89 +/- 12.34 kg; body height 1.90 +/- 0.05 m).
The knee extensor and flexor muscle peak torque of each leg were concentrically
measured at 60o/s and 180o/s with an isokinetic dynamometer. The Squat Jump and
Countermovement Jump were performed on a force platform to determine power and
vertical jump height. Non-significant differences were observed between legs in
the isokinetic knee extension (dominant= 2.91 +/- 0.53 Nm/kg vs non-dominant =
2.70 +/- 0.47 Nm/kg at 60o/s; dominant = 1.90 +/- 0.31 Nm/kg vs non-dominant =
1.83 +/- 0.29 Nm/kg at 180o/s) and flexion peak torques (dominant = 1.76 +/- 0.29
Nm/kg vs non-dominant = 1.72 +/- 0.39 Nm/kg at 60o/s; dominant = 1.30 +/- 0.23
Nm/kg vs non-dominant = 1.27 +/- 0.35 Nm/kg at 180o/s). Low and non-significant
correlation coefficients were found between the isokinetic peak torques and
vertical jumping performance (SJ = 31.21 +/- 4.32 cm; CMJ = 35.89 +/- 4.20 cm).
Similar isokinetic strength was observed between the legs; therefore, no
relationship was found between the isokinetic knee flexion and extension peak
torques as well as vertical jumping performance in elite handball players.
PMID- 25114750
TI - Fitness profiles of elite portuguese rugby union players.
AB - The aim of this study was to describe the fitness profiles of senior elite
Portuguese rugby players. Forty-six senior Portuguese rugby players, classified
as backs (n=22; age 26.2+/-2.8) and forwards (n=24; age 26.7+/-2.9) were assessed
during physical testing sessions carried out for the Portuguese National rugby
team. The body composition, maximum strength and anaerobic capacity of players
are hypothesized to be important physical characteristics as successful
performance in rugby is predicated on the ability to undertake skilled behaviours
both quickly and whilst withstanding large forces when in contact situations. No
absolute differences were found between the backs and forwards for the speed
performance variables although positional differences were found across all
speeds when assessed relative to body mass since the forwards were significantly
heavier. Coaches and the management team can use this information for monitoring
progressive improvements in the physiological capacities of rugby players. These
physical characteristics of elite rugby players provide normative profiles for
specific positions and should form the basis of developmental programmes for
adolescents.
PMID- 25114751
TI - Physical Fitness Differences between Freestyle and Greco-Roman Junior Wrestlers.
AB - The aim of the present study was to examine physical fitness differences between
Freestyle and Greco-Roman junior wrestlers. One hundred twenty-six junior
wrestlers, comprising 70 Freestyle and 56 Greco-Roman wrestlers, participated in
this study. The somatic and physical fitness profile included body mass, body
height, body mass index, body composition, flexibility, maximal anaerobic power
of the legs and arms, aerobic endurance, hand grip strength, leg and back
strength, and speed. No significant differences were found in the anthropometric
and physical features between Freestyle and Greco-Roman wrestlers. The Greco
Roman wrestlers had a significantly higher level of relative leg power, peak arm
power, relative peak arm power, and relative average arm power than Freestyle
wrestlers (p < 0.05). Greco-Roman wrestlers were significantly faster, had better
agility, and had a greater level of leg strength than Freestyle wrestlers, but
Freestyle wrestlers were more flexible than Greco-Roman wrestlers (p < 0.05).
Discriminant function analysis indicated that peak arm power, agility, speed, and
flexibility were selective factors for the differences between Freestyle and
Greco-Roman wrestlers. In conclusion, the present study indicates that the
differences between these wrestling styles promote physical fitness differences
in elite wrestlers. The results reflect specific features of each wrestling
style.
PMID- 25114752
TI - Knowledge of errors in the teaching-learning process of judo-techniques: osoto
guruma as a case study.
AB - The aim of this article was to suggest some changes in the teaching-learning
process methodology of the judo osoto-guruma technique, establishing the action
sequences and the most frequent technical errors committed when performing them.
The study was carried out with the participation of 45 students with no
experience regarding the fundamentals of judo (21 men and 24 women; age=24.02+/
3.98 years old) from the Bachelor of Science of Physical Activity and Sport
Science at the University of Vigo. The proceeding consisted of a systematic
observation of a video recording registered during the technique execution. Data
obtained were analyzed by means of descriptive statistics and sequential analysis
of T-Patterns (obtained with THEME v.5. Software), identifying: a) the presence
of typical inaccuracies during the technique performance; b) a number of chained
errors affecting body balance, the position of the supporting foot, the blocking
action and the final action of the arms. Findings allowed to suggest some motor
tasks to correct the identified inaccuracies, the proper sequential actions to
make the execution more effective and some recommendations for the use of
feedback. Moreover, these findings could be useful for other professionals in
order to correct the key technical errors and prevent diverse injuries.
PMID- 25114753
TI - Transference of traditional versus complex strength and power training to sprint
performance.
AB - The purpose of this study was to determine the effects of two different strength
power training models on sprint performance. Forty-eight soldiers of the
Brazilian brigade of special operations with at least one year of army training
experience were divided into a control group (CG: n = 15, age: 20.2 +/- 0.7
years, body height: 1.74 +/- 0.06 m, and body mass: 66.7 +/- 9.8 kg), a
traditional training group (TT: n = 18, age: 20.1 +/- 0.7 years, body height:
1.71 +/- 0.05 m, and body mass: 64.2 +/- 4.7 kg), and a complex training group
(CT: n = 15, age: 20.3 +/- 0.8 years, body height: 1.71 +/- 0.07 m; and body
mass: 64.0 +/- 8.8 kg). Maximum strength (25% and 26%), CMJ height (36% and 39%),
mean power (30% and 35%) and mean propulsive power (22% and 28%) in the loaded
jump squat exercise, and 20-m sprint speed (16% and 14%) increased significantly
(p<=0.05) following the TT and CT, respectively. However, the transfer effect
coefficients (TEC) of strength and power performances to 20-m sprint performance
following the TT were greater than the CT throughout the 9-week training period.
Our data suggest that TT is more effective than CT to improve sprint performance
in moderately trained subjects.
PMID- 25114755
TI - Contemporary transcatheter interventions in adult congenital heart disease.
PMID- 25114756
TI - Developing tools to measure quality in congenital catheterization and
interventions: the congenital cardiac catheterization project on outcomes (C3PO).
AB - The broad range of relatively rare procedures performed in pediatric cardiac
catheterization laboratories has made the standardization of care and risk
assessment in the field statistically quite problematic. However, with the
growing number of patients who undergo cardiac catheterization, it has become
imperative that the cardiology community overcomes these challenges to study
patient outcomes. The Congenital Cardiac Catheterization Project on Outcomes was
able to develop benchmarks, tools for measurement, and risk adjustment methods
while exploring procedural efficacy. Based on the success of these efforts, the
collaborative is pursuing a follow-up project, the Congenital Cardiac
Catheterization Project on Outcomes-Quality Improvement, aimed at improving the
outcomes for all patients undergoing catheterization for congenital heart disease
by reducing radiation exposure.
PMID- 25114758
TI - Stem cell therapies in patients with single ventricle physiology.
AB - Single ventricle physiology, especially hypoplastic left heart syndrome, is one
of the most high-risk lesions in children with congenital heart disease, and the
ensuing heart failure remains as a major problem related to adverse outcomes in
these patients. The field of stem cell therapy for heart failure has shown
striking advances during the past 10 years, and many clinical trials using stem
cell technologies have been conducted in adults, which suggest that stem cell
therapy is associated with long-term improvement in cardiac function. Cardiac
progenitor cells have recently been discovered, and their strong regenerative
ability has been demonstrated in several studies. Although no large clinical
trials have been performed in the field of congenital heart disease, recent
investigations indicate that stem cell therapy may hold great potential to treat
children with cardiac defects.
PMID- 25114759
TI - Intravascular stent therapy for coarctation of the aorta.
AB - Intravascular stent therapy is considered a primary therapeutic option for most
adults and adolescents with coarctation of the aorta. This review highlights the
indications, technical considerations, procedural aspects, and limited long-term
outcome data when using this intervention. Stent technology has continued to
evolve with potential for further modifications since its inception in the early
1990s. The best therapeutic approach, e.g., stenting versus surgery, in the
treatment of native coarctation continues to be debated due to the paucity of
long-term clinical and imaging data in both groups.
PMID- 25114757
TI - Multimodality 3-dimensional image integration for congenital cardiac
catheterization.
AB - Cardiac catheterization procedures for patients with congenital and structural
heart disease are becoming more complex. New imaging strategies involving
integration of 3-dimensional images from rotational angiography, magnetic
resonance imaging (MRI), computerized tomography (CT), and transesophageal
echocardiography (TEE) are employed to facilitate these procedures. We discuss
the current use of these new 3D imaging technologies and their advantages and
challenges when used to guide complex diagnostic and interventional
catheterization procedures in patients with congenital heart disease.
PMID- 25114760
TI - Hybrid interventional procedures in congenital heart disease.
AB - The evolution of congenital cardiac surgery has seen significant innovative
advances in collaborative efforts between congenital cardiac surgeons and
interventionalists to provide the least invasive intervention with the greatest
hemodynamic benefit for patients with congenital heart disease. This review looks
at how this collaborative approach has evolved and is being applied to treat a
number of congenital conditions across the age ranges.
PMID- 25114761
TI - Modern medical management of acute ischemic stroke.
AB - The modern management of patients with ischemic stroke begins by having a system
in place that organizes the provision of preventive, acute treatment, and
rehabilitative services. In the acute setting, initial evaluation is aimed at
rapidly establishing a diagnosis by excluding stroke mimics, distinguishing
between ischemic and hemorrhagic strokes, and determining if the patient is a
candidate for treatment with intravenous tissue plasminogen activator (IV-tPA,
alteplase). In some centers, select patients who do not qualify for
administration of IV-tPA may be considered for endovascular intervention. General
measures include the use of platelet antiaggregants, treatment of fever, blood
pressure management, and continuation of statins if the patient has already been
taking them. Post-acute evaluation and management is aimed at secondary
prevention and optimizing recovery, including recognition and treatment of post
stroke depression.
PMID- 25114762
TI - Modern interventional management of stroke.
AB - Acute ischemic stroke continues to be one of the leading causes of disability and
death and is a financial burden to an already taxed health care system. Much
research and investigation has been carried out over the past decade on various
recanalization devices aimed at restoring cerebral blood flow. Despite the
rapidly improving technical abilities of these devices, it has been difficult to
demonstrate corresponding improved clinical outcomes. This article will describe
the application of the most recent generation of these devices and briefly
discuss the ongoing discrepancy between these technical achievements and stroke
outcomes.
PMID- 25114764
TI - Case report: incidental finding of a giant cardiac mass.
AB - Coronary artery fistula (CAF) is a rare anomalous connection between a coronary
artery and another coronary artery, major vessel, or cardiac chamber. Prevalence
of CAF is reportedly 1% to 2% in patients who undergo coronary angiography.1 One
of the most common complications of CAF is formation of a coronary artery
aneurysm (CAA). A study conducted by Said and colleagues in 1995 found that CAA
formation was present in 26% of patients who had proven CAF by way of
angiography.2 Although a precise definition of the term "giant" CAA is still
lacking, it generally refers to a dilatation that exceeds the reference vessel
diameter by four times.3 We report an interesting case of a 38-year-old patient
who was incidentally found to have a presumed large right ventricular aneurysm,
which after an open-heart surgery was identified as a CAF with formation of an
unruptured giant CAA.
PMID- 25114763
TI - Comparison of dexmedetomidine versus propofol for sedation in mechanically
ventilated patients after cardiovascular surgery.
AB - Many cardiovascular surgeries are fast-tracked to extubation and require short
term sedation. Dexmedetomidine and propofol have very different mechanisms of
action and pharmacokinetic profiles that make them attractive sedative agents in
this patient population. Recently, there has been increased use of
dexmedetomidine in the intensive care unit (ICU), but few studies exist or have
been published directly comparing both agents in this setting. We conducted a
retrospective cohort study with patients admitted to the ICU after cardiovascular
surgery from January through June 2011. Adult patients who underwent coronary
artery bypass and/or cardiac valve surgery received either dexmedetomidine or
propofol continuous infusion for short-term sedation after cardiovascular
surgery. The primary end point was time (hours) on mechanical ventilation after
surgery. Secondary end points included ICU length of stay (LOS), hospital LOS,
incidence of delirium, and requirement of a second sedative agent. A total of 352
patients met study inclusion criteria, with 33 enrolled in the dexmedetomidine
group and 319 in the propofol group. Time on mechanical ventilation was shorter
in the dexmedetomidine group (7.4 hours vs. 12.9 hours, P = .042). No difference
was seen in ICU or hospital LOS. The need for a second sedative agent to achieve
optimal sedation (24% vs. 27%, P = .737) and incidence of delirium (9% vs. 7.5%,
P = .747) were similar between both groups. Sedation with dexmedetomidine
resulted in a significant reduction in time on mechanical ventilation. However,
no difference was seen in ICU or hospital LOS, incidence of delirium, or
mortality.
PMID- 25114765
TI - Case report: single coronary artery with ischemia and sudden cardiac arrest.
AB - Single coronary artery (SCA) is a very rare finding. Although most cases of SCA
are found incidentally on coronary angiography, it can potentially lead to
different clinical repercussions.1, 2 Herein we describe a patient with SCA who
had unstable angina with subsequent sudden cardiac arrest, and we provide a brief
review of the recent literature.
PMID- 25114767
TI - Museum of TMH multimodality imaging center: ruptured sinus of valsalva aneurysm
with an odd presentation.
PMID- 25114766
TI - Case report: cardiac tamponade resembling an acute myocardial infarction as the
initial manifestation of metastatic pericardial adenocarcinoma.
AB - Pericardial malignancies are uncommon, usually metastatic, linked to terminal
oncology patients, and rarely diagnosed premortem. A very small number of
patients will develop signs and symptoms of malignant pericardial effusion as
initial clinical manifestation of neoplastic disease. Among these patients, a
minority will progress to a life-threatening cardiac tamponade. It is exceedingly
rare for a cardiac tamponade to be the unveiling clinical manifestation of an
unknown malignancy, either primary or metastatic to pericardium. We present the
case of a 50-year-old male who was admitted to the emergency department with an
acute myocardial infarction diagnosis that turned out to be a cardiac tamponade
of unknown etiology. Further studies revealed a metastatic pericardial
adenocarcinoma with secondary cardiac tamponade. We encourage considering
malignancies metastatic to pericardium as probable etiology for large pericardial
effusions and cardiac tamponade of unknown etiology.
PMID- 25114768
TI - Museum of TMH multimodality imaging center: cardiac amyloidosis.
PMID- 25114769
TI - Points to remember: frequently encountered urologic problems after cardiovascular
surgery.
PMID- 25114774
TI - On being a doctor: ask, why?
PMID- 25114776
TI - 5-(Methylthio)tetrazoles as Versatile Synthons in the Stereoselective Synthesis
of Polycyclic Pyrazolines via Photoinduced Intramolecular Nitrile Imine-Alkene
1,3-Dipolar Cycloaddition.
AB - A key thioether substituent in readily accessible 2-alkyl-5
(methylthio)tetrazoles enables facile photoinduced denitrogenation and
intramolecular nitrile imine 1,3-dipolar cycloaddition to afford a wide range of
polycyclic pyrazoline products with excellent diastereoselectivity. The
methylthio group red-shifts the UV absorbance of the tetrazole, obviating the
requirement in all previous substrate systems for at least one aryl substituent,
and can subsequently be converted into a variety of other functionalities. This
synthetic platform has been applied to the concise total syntheses of the
alkaloid natural products (+/-)-newbouldine and withasomnine.
PMID- 25114777
TI - A study on drug-drug interactions through prescription analysis in a South Indian
teaching hospital.
AB - OBJECTIVE: The objective of this study was to assess the drug-drug interactions
(DDIs) through prescription analysis among the inpatients of a South Indian
teaching hospital. METHODS: The study was a prospective observational
prescription analysis conducted for a period of 6 months, from October 2010 to
March 2011. The prescriptions having two or more drugs and where a DDI was
suspected were selected by the physician in charge of the ward. The drugs in the
prescription were then entered into the drug interaction checker software. The
DDIs were classified based on the mechanism of interactions, severity of
interactions, relation to the number of drugs prescribed, and disease conditions
were also determined. RESULTS: A total of 204 prescriptions were analyzed, of
which 186 prescriptions had 856 DDIs. Most of the DDIs were pharmacokinetic drug
interactions (42%) followed by unknown mechanisms (34%) and pharmacodynamic
mechanisms (24%). The study findings showed that the prescriptions for
cardiovascular with respiratory disease conditions had the greatest number of
drug interactions on average. A severity assessment showed that majority of the
DDIs were moderate (70%) followed by minor (28%). The study results showed that
as the number of drugs increases in a prescription, the number of DDIs also
increases. The interventions determined showed that dosage adjustment (12%) was
to be followed in most of the DDIs. CONCLUSION: This study assists in
understanding the factors associated with DDIs that can help in safe and
effective use of drugs in the future.
PMID- 25114775
TI - SOX2 and cancer: current research and its implications in the clinic.
AB - SOX2 is a gene that encodes for a transcription factor belonging to the SOX gene
family and contains a high-mobility group (HMG) domain, which permits highly
specific DNA binding. Consequently, SOX2 functions as an activator or suppressor
of gene transcription. SOX2 has been described as an essential embryonic stem
cell gene and moreover, a necessary factor for induced cellular reprogramming.
SOX2 research has only recently switched focus from embryogenesis and development
to SOX2's function in disease. Particularly, the role of SOX2 in cancer
pathogenesis has become of interest in the field. To date, studies have shown
SOX2 to be amplified in various cancer types and affect cancer cell physiology
via involvement in complicated cell signaling and protein-protein interactions.
Recent reviews in this field have highlighted SOX2 in mammalian physiology,
development and pathology. In this review, we comprehensively compile what is
known to date about SOX2's involvement in cancer biology, focusing on the most
recent findings in the fields of cellular signaling and cancer stem cells.
Lastly, we underscore the role of SOX2 in the clinic and highlight new findings,
which may provide novel clinical applications for SOX2 as a prognostic marker,
indicator of metastasis, biomarker or potential therapeutic target in some cancer
types.
PMID- 25114778
TI - Drug-related falls in older patients: implicated drugs, consequences, and
possible prevention strategies.
AB - Falls are the leading cause of injuries among older adults, aged 65 years and
older. Furthermore, falls are an increasing public health problem because of
ageing populations worldwide due to an increase in the number of older adults,
and an increase in life expectancy. Numerous studies have identified risk factors
and investigated possible strategies to prevent (recurrent) falls in community
dwelling older people and those living in long-term care facilities. Several
types of drugs have been associated with an increased fall risk. Since drugs are
a modifiable risk factor, periodic drug review among older adults should be
incorporated in a fall prevention programme.
PMID- 25114779
TI - Safety of antiobesity drugs.
AB - Obesity is a major health problem worldwide. Although diet and physical activity
are crucial in the management of obesity, the long-term success rate is low.
Therefore antiobesity drugs are of great interest, especially when lifestyle
modification has failed. As obesity is not an immediate life-threatening disease,
these drugs are required to be safe. Antiobesity drugs that have been developed
so far have limited efficacies and considerable adverse effects affecting
tolerability and safety. Therefore, most antiobesity drugs have been withdrawn.
Fenfluramine and dexfenfluramine were withdrawn because of the potential damage
to heart valves. Sibutramine was associated with an increase in major adverse
cardiovascular events in the Sibutramine Cardiovascular Outcomes (SCOUT) trial
and it was withdrawn from the market in 2010. Rimonabant was withdrawn because of
significant psychiatric adverse effects. Orlistat was approved in Europe and the
United States for long-term treatment of obesity, but many patients cannot
tolerate its gastrointestinal side effects. Phentermine and diethylpropion can
only be used for less than 12 weeks because the long-term safety of these drugs
is unknown. Ephedrine and caffeine are natural substances but the effects on
weight reduction are modest. As a result there is a huge unmet need for effective
and safe antiobesity drugs. Recently lorcaserin and topiramate plus phentermine
have been approved for the treatment of obesity but long-term safety data are
lacking.
PMID- 25114782
TI - Monitoring product safety in the postmarketing environment.
AB - The safety profile of a medicinal product may change in the postmarketing
environment. Safety issues not identified in clinical development may be seen and
need to be evaluated. Methods of evaluating spontaneous adverse experience
reports and identifying new safety risks include a review of individual reports,
a review of a frequency distribution of a list of the adverse experiences, the
development and analysis of a case series, and various ways of examining the
database for signals of disproportionality, which may suggest a possible
association. Regulatory agencies monitor product safety through a variety of
mechanisms including signal detection of the adverse experience safety reports in
databases and by requiring and monitoring risk management plans, periodic safety
update reports and postauthorization safety studies. The United States Food and
Drug Administration is working with public, academic and private entities to
develop methods for using large electronic databases to actively monitor product
safety. Important identified risks will have to be evaluated through
observational studies and registries.
PMID- 25114780
TI - Selective serotonin reuptake inhibitors and torsade de pointes: new concepts and
new directions derived from a systematic review of case reports.
AB - OBJECTIVE: In the light of the recent United States Food and Drug Administration
(FDA) warning to clinicians on using previously approved doses of citalopram
because of the purported higher risk of torsade de pointes (TdP), we pursued the
broader question: are selective serotonin reuptake inhibitor (SSRI)
antidepressant agents as a group unsafe because they might induce QTc interval
prolongation and TdP? METHOD: We reviewed the literature and found only 15 case
reports (6 of fluoxetine, 1 of sertraline and 8 of citalopram) of SSRI-associated
QTc interval prolongation linking to TdP. RESULTS: A total of 13 cases contained
sufficient information for analysis. In the setting of TdP, QTc interval
prolongation does not clearly relate to SSRI dose. CONCLUSION: Applying
conventional statistics as the FDA does may not be the best tool to study this
phenomenon because SSRI-associated TdP is a very rare event and hence best
understood as an 'extreme outlier'. Despite the limitations inherent in case
report material, case reports on drug-associated QTc interval prolongation and
TdP provide valuable information that should be considered along with other
sources of information for clinical guidance.
PMID- 25114783
TI - Preparing for safety issues following drug approval: pre-approval risk management
considerations.
AB - Risk management plans and risk minimization plans as well as postapproval
commitment studies are based on risks identified pre-approval that need to be
further characterized or minimized in the postmarketing environment. Although the
implementation of these activities are conducted in the postapproval arena, the
design of the plans and studies as well as the development of effective
postapproval tools and mitigation strategies should be carried out pre-approval.
The pre-approval period also provides the opportunity to fully understand the
treatment population that is included in the clinical trial program and to
determine how the target population for the drug after approval may differ from
the clinical trial patient population. When regulators or sponsors have expressed
concerns about safety issues identified during clinical development, the result
may be a postapproval commitment in the form of a registry or an observational
safety study or, in the US, a Risk Evaluation and Mitigation Strategy (REMS) as a
condition of approval. Specific examples are given for risk mitigation activities
that can be conducted pre-approval.
PMID- 25114781
TI - Calcium supplements and cardiovascular risk: 5 years on.
AB - Calcium supplements have been widely used by older men and women. However, in
little more than a decade, authoritative recommendations have changed from
encouraging the widespread use of calcium supplements to stating that they should
not be used for primary prevention of fractures. This substantial shift in
recommendations has occurred as a result of accumulated evidence of marginal
antifracture efficacy, and important adverse effects from large randomized
controlled trials of calcium or coadministered calcium and vitamin D supplements.
In this review, we discuss this evidence, with a particular focus on increased
cardiovascular risk with calcium supplements, which we first described 5 years
ago. Calcium supplements with or without vitamin D marginally reduce total
fractures but do not prevent hip fractures in community-dwelling individuals.
They also cause kidney stones, acute gastrointestinal events, and increase the
risk of myocardial infarction and stroke. Any benefit of calcium supplements on
preventing fracture is outweighed by increased cardiovascular events. While there
is little evidence to suggest that dietary calcium intake is associated with
cardiovascular risk, there is also little evidence that it is associated with
fracture risk. Therefore, for the majority of people, dietary calcium intake does
not require close scrutiny. Because of the unfavorable risk/benefit profile,
widespread prescribing of calcium supplements to prevent fractures should be
abandoned. Patients at high risk of fracture should be encouraged to take agents
with proven efficacy in preventing vertebral and nonvertebral fractures.
PMID- 25114784
TI - Associations between different measures of anticholinergic drug exposure and
Barthel Index in older hospitalized patients.
AB - OBJECTIVE: To compare associations between four measures of anticholinergic
exposure (anticholinergic risk scale, ARS; anticholinergic drug burden, DBAC;
number and use versus no use of anticholinergic drugs), Barthel Index (BI,
physical function) and Abbreviated Mental Test (AMT, cognitive function) on
admission in older hospitalized patients. METHODS: Prospective observational
study of a consecutive series of 271 older patients (age 83 +/- 7 years) from
community-dwelling and institutionalized settings, admitted to an acute geriatric
admission unit between 28 September 2011 and 18 December 2011. The main outcome
measures were BI quartiles (primary outcome) and AMT (secondary outcome) on
admission. RESULTS: Anticholinergic prevalence was 47%. Multinomial logistic
regression showed higher DBAC was associated with a greater risk of being in the
lower BI quartiles versus highest BI quartile (Q4). This risk was significant for
Q3 (p = 0.04) and Q2 (p = 0.02) but not for Q1 (p = 0.06). A greater number of
anticholinergic drugs was associated with a higher risk of being in Q2 (p =
0.02). This risk was not significant for either Q3 (p = 0.10) or Q1 (p = 0.06).
No significant associations were observed either with use of anticholinergic
medication or with ARS and BI quartiles. AMT did not show independent
associations with any of the four measures of anticholinergic exposure.
CONCLUSION: In older hospitalized patients, DBAC and some crude measures of
anticholinergic exposure, but not ARS, showed independent associations with lower
BI, but not AMT. These results highlight differences between various measures of
anticholinergic drug exposure when studying their associations with functional
status.
PMID- 25114785
TI - The risk of cutaneous adverse reactions among patients with the HLA-A* 31:01
allele who are given carbamazepine, oxcarbazepine or eslicarbazepine: a
perspective review.
AB - Carbamazepine is a drug that is widely used for the treatment of epilepsy,
trigeminal neuralgia and bipolar disorder. This drug is also known to cause
cutaneous adverse drug reactions (cADRs) in up to 10% of patients. The recent
progress in pharmacogenetics has revealed that human leukocyte antigen (HLA)
genotypes are associated with a susceptibility to the cADRs caused by particular
drugs. For carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal
necrolysis, very strong associations with HLA-B*15:02 have been found mainly in
patients of Southeastern Asian origin. In some countries, prescreening HLA
B*15:02 allele has already been put to practical use as a biomarker to avoid the
life-threatening adverse drug reactions. In this review, another risk factor for
carbamazepine-induced cADRs is discussed, namely HLA-A*31:01. We compare the
strength of the association between HLA-A*31:01 and carbamazepine-induced cADRs
based on reports for various ethnic populations; discuss the difference between
the HLA-A*31:01 and HLA-B*15:02 biomarkers and the usefulness of prescreening HLA
A*31:01 to detect patients at high risk for carbamazepine-induced cADRs; and
refer to points that remain to be resolved.
PMID- 25114786
TI - Safety of long-acting beta agonists and inhaled corticosteroids in children and
adolescents with asthma.
AB - The introduction of long-acting beta agonists (LABAs) was considered a major
advance in bronchodilator therapy for adult, as well as pediatric, patients with
asthma. However, the use of LABAs has raised safety concerns, especially the
potential for severe asthma exacerbations (SAEs) resulting in hospitalizations or
even death. Meanwhile, the use of inhaled corticosteroids (ICSs), a cornerstone
in the treatment of mild-to-severe persistent asthma, has been associated with
growth suppression in children. The purpose of this review was to identify and
discuss the major published safety studies surrounding LABA, ICS, and combined
LABA/ICS usage in children. By way of a critical search for influential published
clinical trials, meta-analyses, and observational studies, six studies relevant
to the safety of LABA monotherapy, seven studies relevant to ICS monotherapy, and
four studies on the subject of LABA/ICS combination usage were identified and
reviewed. Based on the reviewed literature, the controversy surrounding these
anti-asthma medications was clearly exposed. On the one hand, there is some
evidence that LABA monotherapy may be associated with SAEs and asthma-related
death, while ICS monotherapy may be associated with a higher risk of growth
suppression. On the other hand, the concurrent use of a LABA with an ICS has been
associated with positive outcomes including symptom reduction and reduced rate
and severity of exacerbations. Further clinical research is warranted and has
been called for by the US Food and Drug Administration.
PMID- 25114787
TI - Evaluation of side effects of radiofrequency capacitive hyperthermia with
magnetite on the blood vessel walls of tumor metastatic lesion surrounding the
abdominal large vessels: an agar phantom study.
AB - BACKGROUND: Magnetite used in an 8-MHz radiofrequency (RF) capacitive heating
device can increase the temperature of a specific site up to 45 degrees C. When
treating a metastatic lesion around large abdominal vessels via hyperthermia with
magnetite, heating-induced adverse effects on these vessels need to be
considered. Therefore, this study examined hyperthermia-induced damage to blood
vessel walls in vitro. METHODS: A large agar phantom with a circulatory system
consisting of a swine artery and vein connected to a peristaltic pump was
prepared. The blood vessels were placed on the magnetite-containing agar piece.
Heating was continued for 30 min at 45 degrees C. After heating, a histological
study for injury to the blood vessels was performed. RESULTS: The inner membrane
temperature did not reach 45 degrees C due to the cooling effect of the blood
flow. In the heated vessels, vascular wall collagen degenerated and smooth muscle
cells were narrowed; however, no serious changes were noted in the vascular
endothelial cells or vascular wall elastic fibers. The heated vessel wall was not
severely damaged; this was attributed to cooling by the blood flow. CONCLUSIONS:
Our findings indicate that RF capacitive heating therapy with magnetite may be
used for metastatic lesions without injuring the surrounding large abdominal
vessels.
PMID- 25114788
TI - Active video gaming in patients with renal transplant: a pilot study.
AB - BACKGROUND: Patients with renal transplant are at higher risk of mortality from
cardiovascular disease (CVD) compared with the general population. Physical
activity has been shown to reduce the risk of CVD mortality in these patients.
Unfortunately, barriers such as the harsh Canadian climate prevent patients from
engaging in and harvesting the health benefits of physical activity. This pilot
study explored active video gaming (AVG) as a way for patients with renal
transplant to obtain physical activity and examined its effect on their
functional status and quality of life (QOL). MAIN TEXT: We recruited nine
patients for an 8-week prospective pilot study. All patients received a Microsoft
Xbox 360TM video gaming console, a Microsoft KinectTM sensor, and the video game
Your Shape Fitness Evolved 2012. Assessment of each participant before and after
the intervention included blood pressure measures, a 6-minute walk test, and the
Godin Leisure Time Questionnaire (GLTQ). We analyzed all nine patients at the end
of the 8-week study period, and found no changes in blood pressure or GLTQ
scores. However, there was a significant increase in the 6-minute walk distance
(P = 0.022), which represented a consistent increase for most patients
(correlation = 0.977). In addition, participants over the age of 45 years (n = 4)
were more likely to use the AVG system (P = 0.042). CONCLUSION: AVG has the
potential to improve the functional status in patients with renal transplant.
Further research is required to corroborate the full health benefits of AVG in
this patient population.
PMID- 25114789
TI - The efficacy and safety of pramipexole ER versus IR in Chinese patients with
Parkinson's disease: a randomized, double-blind, double-dummy, parallel-group
study.
AB - OBJECTIVE: To evaluate the non-inferiority of pramipexole extended-release (ER)
versus immediate-release (IR) in Chinese patients with Parkinson's disease (PD)
in a double-blind, randomized, parallel-group study. METHODS: Subjects were
Chinese patients with idiopathic PD with diagnosis >= 2 years prior to trial, age
>= 30 years old at diagnosis, and Modified Hoehn and Yahr score 2-4 during 'on'
time. Subjects received treatment with pramipexole ER (n=234) or IR (n=239). Non
inferiority was based on the primary endpoint, the change from baseline to end of
maintenance (week 18) in the UPDRS (Parts II + III) total score. RESULTS: For the
primary endpoint, the adjusted mean changes (standard error) of UPDRS Parts II +
III at week 18 were -13.81 (0.655) and -13.05 (0.643) for ER and IR formulations,
respectively, using ANCOVA adjusted for treatment and centre (fixed effect) and
baseline (covariate). The adjusted mean between group difference was 0.8 for the
2-sided 95% CI (-1.047, 2.566). Since the lower limit of the 2-sided 95% CI (
1.047) for treatment difference was higher than the non-inferiority margin of -4,
non-inferiority between pramipexole ER and IR was demonstrated. The incidence of
adverse events (AEs) was 68.8% in the ER arm and 73.6% in the IR arm with few
severe AEs (ER: 2.1%; IR: 3.8%). CONCLUSION: Based on the UPDRS II + III score,
pramipexole ER was non-inferior to pramipexole IR. The safety profiles of
pramipexole ER and IR were similar. These results were based on comparable mean
daily doses and durations of treatment for both formulations.
PMID- 25114790
TI - Measles-mumps-rubella vaccination timing and autism among young African American
boys: a reanalysis of CDC data.
AB - BACKGROUND: A significant number of children diagnosed with autism spectrum
disorder suffer a loss of previously-acquired skills, suggesting
neurodegeneration or a type of progressive encephalopathy with an etiological
basis occurring after birth. The purpose of this study is to investigate the
effectof the age at which children got their first Measles-Mumps-Rubella (MMR)
vaccine on autism incidence. This is a reanalysis of the data set, obtained from
the U.S. Centers for Disease Control and Protection (CDC), used for the Destefano
et al. 2004 publication on the timing of the first MMR vaccine and autism
diagnoses. METHODS: The author embarked on the present study to evaluate whether
a relationship exists between child age when the first MMR vaccine was
administered among cases diagnosed with autism and controls born between 1986
through 1993 among school children in metropolitan Atlanta. The Pearson's chi
squared method was used to assess relative risks of receiving an autism diagnosis
within the total cohort as well as among different race and gender categories.
RESULTS: When comparing cases and controls receiving their first MMR vaccine
before and after 36 months of age, there was a statistically significant increase
in autism cases specifically among African American males who received the first
MMR prior to 36 months of age. Relative risks for males in general and African
American males were 1.69 (p=0.0138) and 3.36 (p=0.0019), respectively.
Additionally, African American males showed an odds ratio of 1.73 (p=0.0200) for
autism cases in children receiving their first MMR vaccine prior to 24 months of
age versus 24 months of age and thereafter. CONCLUSIONS: The present study
provides new epidemiologic evidence showing that African American males receiving
the MMR vaccine prior to 24 months of age or 36 months of age are more likely to
receive an autism diagnosis.
PMID- 25114791
TI - A review of the use of health examination data from the Health Survey for England
in government policy development and implementation.
AB - BACKGROUND: Information is needed at all stages of the policy making process. The
Health Survey for England (HSE) is an annual cross-sectional health examination
survey of the non-institutionalised general population in England. It was
originally set up to inform national policy making and monitoring by the
Department of Health. This paper examines how the nurse collected physical and
biological measurement data from the HSE have been essential or useful for
identification of a health issue amenable to policy intervention; initiation,
development or implementation of a strategy; choice and monitoring of targets; or
assessment and evaluation of policies. METHODS: Specific examples of use of HSE
data were identified through interviews with senior members of staff at the
Department of Health and the Health and Social Care Information Centre. Policy
documents mentioned by interviewees were retrieved for review, and reference
lists of associated policy documents checked. Systematic searches of Chief
Medical Officer Reports, Government 'Command Papers', and clinical guidance
documents were also undertaken. RESULTS: HSE examination data have been used at
all stages of the policy making process. Data have been used to identify an issue
amenable to policy-intervention (e.g. quantifying prevalence of undiagnosed
chronic kidney disease), in strategy development (in models to inform chronic
respiratory disease policy), for target setting and monitoring (the 1992 blood
pressure target) and in evaluation of health policy (the effect of the smoking
ban on second hand smoke exposure). CONCLUSIONS: A health examination survey is a
useful part of a national health information system.
PMID- 25114792
TI - Factors associated with data quality in the routine health information system of
Benin.
AB - BACKGROUND: Routine health information systems (RHIS) are crucial to the
acquisition of data for health sector planning. In developing countries, the
insufficient quality of the data produced by these systems limits their
usefulness in regards to decision-making. The aim of this study was to identify
the factors associated with poor data quality in the RHIS in Benin. METHODS: This
cross-sectional descriptive and analytical study included health workers who were
responsible for data collection in public and private health centers. The
technique and tools used were an interview with a self-administered
questionnaire. The dependent variable was the quality of the data. The
independent variables were socio-demographic and work-related characteristics,
personal and work-related resources, and the perception of the technical factors.
The quality of the data was assessed using the Lot Quality Assurance Sampling
method. We used survival analysis with univariate proportional hazards (PH) Cox
models to derive hazards ratios (HR) and their 95% confidence intervals (95% CI).
Focus group data were evaluated with a content analysis. RESULTS: A significant
link was found between data quality and level of responsibility (p = 0.011),
sector of employment (p = 0.007), RHIS training (p = 0.026), level of work
engagement (p < 0.001), and the level of perceived self-efficacy (p = 0.03). The
focus groups confirmed a positive relationship with organizational factors such
as the availability of resources, supervision, and the perceived complexity of
the technical factors. CONCLUSION: This exploratory study identified several
factors associated with the quality of the data in the RHIS in Benin. The results
could provide strategic decision support in improving the system's performance.
PMID- 25114794
TI - Community based interventions for the prevention and control of Non-Helmintic
NTD.
AB - In this paper, we aim to systematically analyze the effectiveness of community
based interventions (CBI) for the prevention and control of non-helminthic
diseases including dengue, trypanosomiasis, chagas, leishmaniasis, buruli ulcer,
leprosy and trachoma. We systematically reviewed literature published up to May
2013 and included 62 studies in this review. Findings from our review suggest
that CBI including insecticide spraying; insecticide treated bednets and
curtains; community education and cleanliness campaigns; chemoprophylaxis through
mass drug administration; and treatment have the potential to reduce the
incidence and burden of non-helminthic diseases. Lack of data limited the
subgroup analysis for integrated and non-integrated delivery strategies however,
qualitative synthesis suggest that integrated delivery is more effective when
compared to vertical interventions; however, such integration was possible only
because of the existing vertical vector control programs. Community delivered
interventions have the potential to achieve wider coverage and sustained
community acceptance. Eradicating these diseases will require a multipronged
approach including drug administration, health education, vector control and
clean water and sanitation facilities. This would require high level governmental
commitment along with strong partnerships among major stakeholders.
PMID- 25114793
TI - Community-based interventions for the prevention and control of helmintic
neglected tropical diseases.
AB - In this paper, we aim to systematically analyze the effectiveness of community
based interventions (CBIs) for the prevention and control of helminthiasis
including soil-transmitted helminthiasis (STH) (ascariasis, hookworms, and
trichuriasis), lymphatic filariasis, onchocerciasis, dracunculiasis, and
schistosomiasis. We systematically reviewed literature published before May 2013
and included 32 studies in this review. Findings from the meta-analysis suggest
that CBIs are effective in reducing the prevalence of STH (RR: 0.45, 95% CI:
0.38, 0.54), schistosomiasis (RR: 0.40, 95% CI: 0.33, 0.50), and STH intensity
(SMD: -3.16, 95 CI: -4.28, -2.04). They are also effective in improving mean
hemoglobin (SMD: 0.34, 95% CI: 0.20, 0.47) and reducing anemia prevalence (RR:
0.90, 95% CI: 0.85, 0.96). However, it did not have any impact on ferritin,
height, weight, low birth weight (LBW), or stillbirths. School-based delivery
significantly reduced STH (RR: 0.49, 95% CI: 0.39, 0.63) and schistosomiasis
prevalence (RR: 0.50, 95% CI: 0.33, 0.75), STH intensity (SMD: -0.22, 95% CI:
0.26, -0.17), and anemia prevalence (RR: 0.87, 95% CI: 0.81, 0.94). It also
improved mean hemoglobin (SMD: 0.24, 95% CI: 0.16, 0.32). We did not find any
conclusive evidence from the quantitative synthesis on the relative effectiveness
of integrated and non-integrated delivery strategies due to the limited data
available for each subgroup. However, the qualitative synthesis from the included
studies supports community-based delivery strategies and suggests that integrated
prevention and control measures are more effective in achieving greater coverage
compared to the routine vertical delivery, albeit it requires an existing strong
healthcare infrastructure. Current evidence suggests that effective community
based strategies exist and deliver a range of preventive, promotive, and
therapeutic interventions to combat helminthic neglected tropical diseases
(NTDs). However, there is a need to implement and evaluate efficient integrated
programs with the existing disease control programs on a larger scale throughout
resource-limited regions especially to reach the unreachable.
PMID- 25114796
TI - Biomineralized matrix-assisted osteogenic differentiation of human embryonic stem
cells.
AB - The physical and chemical properties of a matrix play an important role in
determining various cellular behaviors, including lineage specificity. We
demonstrate that the differentiation commitment of human embryonic stem cells
(hESCs), both in vitro and in vivo, can be solely achieved through synthetic
biomaterials. hESCs were cultured using mineralized synthetic matrices mimicking
a calcium phosphate (CaP)-rich bone environment differentiated into osteoblasts
in the absence of any osteogenic inducing supplements. When implanted in vivo,
these hESC-laden mineralized matrices contributed to ectopic bone tissue
formation. In contrast, cells within the corresponding non-mineralized matrices
underwent either osteogenic or adipogenic fate depending upon the local cues
present in the microenvironment. To our knowledge, this is the first
demonstration where synthetic matrices are shown to induce terminal cell fate
specification of hESCs exclusively by biomaterial-based cues both in vitro and in
vivo. Technologies that utilize tissue specific cell-matrix interactions to
control stem cell fate could be a powerful tool in regenerative medicine. Such
approaches can be used as a tool to advance our basic understanding and assess
the translational potential of stem cells.
PMID- 25114795
TI - Impact of community-based interventions for the prevention and control of malaria
on intervention coverage and health outcomes for the prevention and control of
malaria.
AB - In this paper, we aim to evaluate the effectiveness of community-based
interventions (CBIs) for the prevention and management of malaria. We conducted a
systematic review and identified 42 studies for inclusion. Twenty-five of the
included studies evaluated the impact of the community-based distribution of
insecticide-treated nets (ITNs), indoor residual spraying (IRS), or impregnated
bed sheets; 14 studies evaluated intermittent preventive therapy (IPT) delivered
in community settings; two studies focused on community-based education for
malaria prevention; and one study evaluated environmental management through
drain cleaning. Our analysis suggests that, overall, the community-based delivery
of interventions to prevent and control malaria resulted in a significant
increase in ITNs ownership (RR: 2.16, 95% CI: 1.86, 2.52) and usage (RR: 1.77,
95% CI: 1.48, 2.11). However, usage of ITNs was limited to two-thirds of the
population who owned them. Community-based strategies also led to a significant
decrease in parasitemia (RR: 0.56, 95% CI: 0.42, 0.74), malaria prevalence (RR:
0.46, 95% CI: 0.29, 0.73), malaria incidence (RR: 0.70, 95% CI: 0.54, 0.90), and
anemia prevalence (RR: 0.79, 95% CI: 0.64, 0.97). We found a non-significant
impact on splenomegaly, birth outcomes (low birth weight, prematurity,
stillbirth/miscarriage), anthropometric measures (stunting, wasting, and
underweight), and mortality (all-cause and malaria-specific). The subgroup
analysis suggested that community-based distribution of ITNs, impregnated bed
sheets and IRS, and IPT are effective strategies. Qualitative synthesis suggests
that high coverage could be achieved at a lower cost with the integration of CBIs
with existing antenatal care and immunization campaigns. Community-based delivery
of interventions to prevent and control malaria are effective strategies to
improve coverage and access and reduce malaria burden, however, efforts should
also be concerted to prevent over diagnosis and drug resistance.
PMID- 25114797
TI - Rapid clearance of epigenetic protein reporters from wound edge cells in
Drosophila larvae does not depend on the JNK or PDGFR/VEGFR signaling pathways.
AB - The drastic cellular changes required for epidermal cells to dedifferentiate and
become motile during wound closure are accompanied by changes in gene
transcription, suggesting corresponding alterations in chromatin. However, the
epigenetic changes that underlie wound-induced transcriptional programs remain
poorly understood partly because a comprehensive study of epigenetic factor
expression during wound healing has not been practical. To determine which
chromatin modifying factors might contribute to wound healing, we screened
publicly available fluorescently-tagged reporter lines in Drosophila for altered
expression at the wound periphery during healing. Thirteen reporters tagging
seven different proteins showed strongly diminished expression at the wound edge.
Three downregulated proteins, Osa, Kismet, and Spt6, are generally associated
with active chromatin, while four others, Sin3A, Sap130, Mi-2, and Mip120, are
associated with repressed chromatin. In all cases reporter down regulation was
independent of the Jun N-terminal Kinase and Pvr pathways, suggesting that novel
signals control reporter clearance. Taken together, our results suggest that
clearance of chromatin modifying factors may enable wound edge cells to rapidly
and comprehensively change their transcriptional state following tissue damage.
PMID- 25114798
TI - Donor Heart Utilization following Cardiopulmonary Arrest and Resuscitation:
Influence of Donor Characteristics and Wait Times in Transplant Regions.
AB - Background. Procurement of hearts from cardiopulmonary arrest and resuscitated
(CPR) donors for transplantation is suboptimal. We studied the influences of
donor factors and regional wait times on CPR donor heart utilization. Methods.
From UNOS database (1998 to 2012), we identified 44,744 heart donors, of which
4,964 (11%) received CPR. Based on procurement of heart for transplantation, CPR
donors were divided into hearts procured (HP) and hearts not procured (HNP)
groups. Logistic regression analysis was used to identify predictors of heart
procurement. Results. Of the 4,964 CPR donors, 1,427 (28.8%) were in the HP
group. Donor characteristics that favored heart procurement include younger age
(25.5 +/- 15 yrs versus 39 +/- 18 yrs, P <= 0.0001), male gender (34% versus 23%,
P <= 0.0001), shorter CPR duration (<15 min versus >30 min, P <= 0.0001), and
head trauma (60% versus 15%). Among the 11 UNOS regions, the highest procurement
was in Region 1 (37%) and the lowest in Region 3 (24%). Regional transplant
volumes and median waiting times did not influence heart procurement rates.
Conclusions. Only 28.8% of CPR donor hearts were procured for transplantation.
Factors favoring heart procurement include younger age, male gender, short CPR
duration, and traumatic head injury. Heart procurement varied by region but not
by transplant volumes or wait times.
PMID- 25114799
TI - Intravitreal bevacizumab alone or combined with macular laser photocoagulation
for recurrent or persistent macular edema secondary to branch retinal vein
occlusion.
AB - Background. To evaluate the efficacy of intravitreal bevacizumab (IVB) injection
with or without macular laser photocoagulation (MLP) for recurrent or persistent
macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Methods.
Thirty-four eyes underwent IVB injection for ME secondary to BRVO as a primary
treatment. Twenty of the 34 eyes experienced recurrent or persistent ME after the
first IVB. Nine of the 20 eyes (Group 1) were retreated with IVB combined with
MLP. The remaining 11 eyes (Group 2) were retreated with IVB alone. Results. In
Group 1, the postoperative best corrected visual acuity (BCVA) improved compared
with the preoperative value at all follow-up visits, although no statistically
significant improvement was observed at 6 months. In contrast, BCVA significantly
improved from 0.53 to 0.40 at 6 months (P < 0.05) in Group 2. Conclusion.
Combined therapy tended to have a smaller effect on visual acuity compared with
IVB monotherapy.
PMID- 25114800
TI - The trajectory and the related physical and social determinants of body mass
index in elementary school children: results from the child and adolescent
behaviors in long-term evolution study.
AB - This study explored developmental trajectory patterns of BMI and associated
factors. Participants included 1,609 students who were followed from age 7 to 12
years. Data collection involved annual self-administered questionnaires and
records of height and weight. An ecological model was used to identify the
factors associated with BMI trajectories. Group-based trajectory models and
multinomial logit models were used in the statistical analysis. There were gender
differences in BMI trajectories. Among boys, four BMI trajectories were normal or
slightly underweight, persistently normal weight, overweight becoming obese, and
persistently obese. Among girls, four BMI trajectories were persistently slightly
underweight, persistently normal weight, persistently overweight, and
persistently obese. The mean BMI in each trajectory group demonstrated an upward
trend over time. In boys, BMI trajectories were significantly associated with
after-school exercise, academic performance, family interactions, overweight
parents, and father's education level. In girls, BMI trajectories were
significantly associated with television viewing or computer use, family
interactions, peer interactions, and overweight parents. Children under age 7
years who are already overweight or obese are an important target for
interventions. The different factors associated with BMI trajectories can be used
for targeting high risk groups.
PMID- 25114802
TI - Biologic collagen cylinder with skate flap technique for nipple reconstruction.
AB - A surgical technique using local tissue skate flaps combined with cylinders made
from a naturally derived biomaterial has been used effectively for nipple
reconstruction. A retrospective review of patients who underwent nipple
reconstruction using this technique was performed. Comorbidities and type of
breast reconstruction were collected. Outcome evaluation included complications,
surgical revisions, and nipple projection. There were 115 skate flap
reconstructions performed in 83 patients between July 2009 and January 2013.
Patients ranged from 32 to 73 years old. Average body mass index was 28.0. The
most common comorbidities were hypertension (39.8%) and smoking (16.9%). After
breast reconstruction, 68.7% of the patients underwent chemotherapy and 20.5%
underwent radiation. Seventy-one patients had immediate breast reconstruction
with expanders and 12 had delayed reconstruction. The only reported complications
were extrusions (3.5%). Six nipples (5.2%) in 5 patients required surgical
revision due to loss of projection; two patients had minor loss of projection but
did not require surgical revision. Nipple projection at time of surgery ranged
from 6 to 7 mm and average projection at 6 months was 3-5 mm. A surgical
technique for nipple reconstruction using a skate flap with a graft material is
described. Complications are infrequent and short-term projection measurements
are encouraging.
PMID- 25114801
TI - Exploration of the Effect of Tobacco Smoking on Metabolic Measures in Young
People Living with HIV.
AB - We conducted cross-sectional, multicenter studies in HIV-positive young women and
men to assess metabolic and morphologic complications from tobacco smoking in 372
behaviorally infected HIV-positive youth, aged 14-25 years. Measurements included
self-reported tobacco use, fasting lipids, glucose, fat distribution, and bone
mineral density (BMD; dual-energy X-ray absorptiometry scans). Overall, 144
(38.7%) self-reported smoking tobacco and 69 (47.9%) of these reported smoking
greater than five cigarettes per day. Smokers versus nonsmokers had lower mean
total cholesterol (146.0 versus 156.1 mg/dL; P < 0.01) and lower mean total body
fat percent (24.1% versus 27.2%, P = 0.03). There was no difference between
smokers and nonsmokers in fasting glucose or BMD. There appear to be only minimal
effects from tobacco smoking on markers of cardiac risk and bone health in this
population of HIV-positive youth. While these smokers may not have had sufficient
exposure to tobacco to detect changes in the outcome measures, given the long
term risks associated with smoking and HIV, it is critical that we encourage HIV
positive youth smokers to quit before the deleterious effects become apparent.
PMID- 25114803
TI - Tsc2 Haploinsufficiency Has Limited Effects on Fetal Brain Cytokine Levels during
Gestational Immune Activation.
AB - Dysregulated TSC/mTOR signaling may play a pathogenetic role in forms of
syndromic autism, such as autism associated with tuberous sclerosis, a genetic
disorder caused by heterozygous TSC1 or TSC2 mutations. Environmental risk
factors, such as gestational viral infections, may, in some cases, also
contribute to the pathogenesis of autism and related neuropsychiatric disorders.
We have recently found that a heterozygous Tsc2 mutation and the poly I:C model
of maternal immune activation (MIA) interactively perturb fetal development and
adult social behavior in mice, suggesting that these factors converge on shared
pathways. TSC/mTOR signaling plays an important role in the modulation of immune
responses, raising the possibility that the damage caused by MIA was greater in
Tsc2(+/-) than in wildtype fetuses because of an exacerbated immune response in
the mutants. Here, cytokine antibody arrays were employed to measure relative
cytokine abundances in the fetal brain and the placenta during MIA. Cytokines
were induced by gestational poly I:C but there was no obvious modulatory effect
of Tsc2 haploinsufficiency. The data indicate that cytokine exposure during MIA
is comparable in Tsc2 haploinsufficient and wildtype control fetuses, suggesting
that downstream molecular and cellular processes may account for the interactive
effects of Tsc2 haploinsufficiency and MIA.
PMID- 25114804
TI - Lifestyle and Dietary Behaviors among Saudi Preschool Children Attending Primary
Health Care Centers, Eastern Saudi Arabia.
AB - Objective. To study life styles and dietary behaviors among Saudi preschool
children (1-5 years) attending primary health care centers (PHCCs) in Dammam and
Qatif areas, eastern province, Saudi Arabia. Material and Methods. Cross
sectional study. Data were collected using structured, interviewer-filled
questionnaire. Children and their mothers were encountered during their well-baby
clinic visits. A total number of 300 preschool children and their mothers were
interviewed during study period. Results. Unsatisfactory areas include smoking
fathers (32%), smoking in front of children (11.3%), overweight and obesity among
mothers (60.3%), noncompliance using seat belts for both parents (56.3%) and
children (68%), children watching television (T.V) more than 2 hours (50%),
adherence to exclusive breast feeding (only 20.7%), and late solid food
introduction (65.3%). Frequent intake of unhealthy food items was 26%, 25%, and
24% for pizza, burger, and soft drinks. Unfortunately frequent intake of the
following unhealthy food items was high: biscuits, deserts/chocolates, and chips
which was 78%, 67%, and 72%, respectively. Conclusion. This study provides
benchmark about the current situation. It provides health care workers and
decision makers with important information that may help to improve health
services.
PMID- 25114805
TI - Emergency sonography AIDS diagnostic accuracy of torso injuries: a study in a
resource limited setting.
AB - Introduction. Clinical evaluation of patients with torso trauma is often a
diagnostic challenge. Extended focused assessment with sonography for trauma
(EFAST) is an emergency ultrasound scan that adds to the evaluation of
intrathoracic abdominal and pericardial cavities done in FAST (focused assessment
with sonography for trauma). Objective. This study compares EFAST (the index
test) with the routine standard of care (SoC) investigations (the standard
reference test) for torso trauma injuries. Methods. A cross-sectional descriptive
study was conducted over a 3-month period. Eligible patients underwent EFAST
scanning and the SoC assessment. The diagnostic accuracy of EFAST was calculated
using sensitivity and specificity scores. Results. We recruited 197 patients; the
M : F ratio was 5 : 1, with mean age of 27 years (SD 11). The sensitivity of
EFAST was 100%, the specificity was 97%, the PPV was 87%, and the NPV was 100%.
It took 5 minutes on average to complete an EFAST scan. 168 (85%) patients were
EFAST-scanned. Most patients (82) (48%) were discharged on the same day of
hospitalization, while 7 (4%) were still at the hospital after two weeks. The
mortality rate was 18 (9%). Conclusion. EFAST is a reliable method of diagnosing
torso injuries in a resource limited context.
PMID- 25114807
TI - Failure of ketamine anesthesia in a patient with lamotrigine overdose.
AB - Introduction. It is important to know which clinical situations prevent ketamine
from working. Case Report. We present the case of the psychiatric inpatient who
was admitted to our emergency department after ingesting a toxic dose of
lamotrigine, unknown at that time. On admission, she was clearly in distress,
displaying extreme agitation and violent ataxic movements. We opted to achieve
sedation using intravenous ketamine boluses. Unexpectedly, after being injected
with a total of 250 mg ketamine, our patient displayed no signs of dissociative
anaesthesia. Discussion. There was no apparent reason for why ketamine failed,
but an interaction between lamotrigine and ketamine was suspected. A literature
search was performed. Very few articles describe interactions between lamotrigine
and ketamine. Experimental studies, however, demonstrate how lamotrigine
attenuates the neuropsychiatric effects of ketamine. Ketamine is classically
described as an NMDA antagonist. Ketamine's dissociative effects, however, are
thought to be mediated by increased glutamate release via a pathway not dependent
on NMDA receptors. Lamotrigine, on the other hand, is known to reduce cortical
glutamate release. Conclusion. Lamotrigine reduces the glutamate release needed
to mediate ketamine's dissociative anaesthesia. This is important knowledge for
anaesthesiologists in the emergency room where ketamine is often administered to
unstable patients.
PMID- 25114806
TI - Combination of acellular nerve graft and schwann cells-like cells for rat sciatic
nerve regeneration.
AB - OBJECTIVE: To investigate the effect of tissue engineering nerve on repair of rat
sciatic nerve defect. METHODS: Forty-five rats with defective sciatic nerve were
randomly divided into three groups. Rats in group A were repaired by acellular
nerve grafts only. Rats in group B were repaired by tissue engineering nerve. In
group C, rats were repaired by autogenous nerve grafts. After six and twelve
weeks, sciatic nerve functional index (SFI), neural electrophysiology (NEP),
histological and transmission electron microscope observation, recovery ratio of
wet weight of gastrocnemius muscle, regenerated myelinated nerve fibers number,
nerve fiber diameter, and thickness of the myelin sheath were measured to assess
the effect. RESULTS: After six and twelve weeks, the recovery ratio of SFI and
wet weight of gastrocnemius muscle, NEP, and the result of regenerated myelinated
nerve fibers in groups B and C were superior to that of group A (P < 0.05), and
the difference between groups B and C was not statistically significant (P >
0.05). CONCLUSION: The tissue engineering nerve composed of acellular allogenic
nerve scaffold and Schwann cells-like cells can effectively repair the nerve
defect in rats and its effect was similar to that of the autogenous nerve grafts.
PMID- 25114808
TI - CTCFL (BORIS) mRNA Expression in a Peripheral Giant Cell Granuloma of the Oral
Cavity.
AB - Peripheral giant cell granuloma (PGCG) is a relatively common benign reactive
lesion of the oral cavity which can occur at any age. CTCFL/BORIS (CTCF
like/Brother of the Regulator of Imprinted Sites) and CTCF (CCCTC-binding factor)
are paralogous genes with an important role in the regulation of gene expression,
genomic imprinting, and nuclear chromatin insulators regulation. BORIS expression
promotes cell immortalization and growth while CTCF has tumor suppressor
activity; the expression pattern may reflect the reverse transcription silencing
of BORIS. The aim of this work was to describe a histopathological and molecular
approach of an 8-year-old pediatric male patient with PGCG diagnosis. It was
observed that the PGCG under study expressed CTCF as well as BORIS mRNAs
alongside with the housekeeping gene GAPDH, which may be related to possible
genetic and epigenetic changes in normal cells of oral cavity.
PMID- 25114809
TI - Odontogenic keratocyst mimicking paradental cyst.
AB - Objective. The aim of this paper is to present an uncommon clinical and
radiographic aspect of odontogenic keratocyst (OKC) mimicking paradental cyst.
Methods. A 32-year-old female patient showed a well-delimited radiolucent lesion
connected with the root of the left third molar with close anatomical
relationship with the mandibular canal. The clinical, radiographic, and
anamnestic features lead us to diagnose a paradental cyst that was treated by
enucleation after extraction of the partially impacted tooth. Results.
Histological analysis showed typical histological features of PKC such as the
presence of a lining of stratified squamous epithelium with a well-defined basal
layer of palisading columnar of cuboidal cells. Conclusion. Initial X-ray
analysis and the position of the lesion related to the third mandibular tooth
caused us to mistakenly diagnose a paradental cyst. We were only able to identify
the cyst as an PKC rather than a paradental cyst after histological analysis.
PMID- 25114810
TI - Acute Testicular Ischemia following Endovascular Abdominal Aortic Aneurysm Repair
Identified in the Emergency Department.
AB - Endovascular aneurysm repair (EVAR) is perhaps the most widely utilized surgical
procedure for patients with large abdominal aortic aneurysms. This procedure is
minimally invasive and reduces inpatient hospitalization requirements. The case
involves a 72-year-old male who presented to the emergency department with right
testicular ischemia two days following EVAR. Given the minimal inpatient
hospitalization associated with this procedure, emergency physicians are likely
to encounter associated complications. Ischemic and thromboembolic events
following EVAR are extremely rare but require prompt vascular surgery
intervention to minimize morbidity and mortality.
PMID- 25114812
TI - Long-Term Follow-Up of a Child with Autoimmune Thyroiditis and Recurrent
Hyperthyroidism in the Absence of TSH Receptor Antibodies.
AB - Hashitoxicosis is an initial, transient, hyperthyroid phase that rarely affects
patients with Hashimoto thyroiditis. We present here an unusual case of a child
with Hashimoto thyroiditis and recurrent hyperthyroidism. A 4 yr 6/12 old male
was diagnosed by us with autoimmune subclinical hypothyroidism (normal free T4,
slightly elevated TSH, and elevated TG antibody titer). Two years and 6/12 later
he experienced increased appetite and poor weight gain; a laboratory evaluation
revealed suppressed TSH, elevated free T4, and normal TSI titer. In addition, an
I(123) thyroid uptake was borderline-low. A month later, the free T4 had
normalized. After remaining asymptomatic for 3 years, the patient presented again
with increased appetite, and he was found with low TSH and high free T4. Within
the following 3 months, his free T4 and TSH normalized. At his most recent
evaluation, his TSH was normal and the free T4 was borderline-high; the TG
antibody titer was still elevated and the TSI titer was negative. To our
knowledge, this is the first patient reported with Hashimoto thyroiditis and
recurrent hyperthyroidism. This case exemplifies the variability of the
manifestations and natural history of Hashimoto thyroiditis and supports the need
for a long-term evaluation of patients with autoimmune thyroid disease.
PMID- 25114811
TI - Pneumomediastinum in blunt chest trauma: a case report and review of the
literature.
AB - Blunt trauma is the most common mechanism of injury in patients with
pneumomediastinum and may occur in up to 10% of patients with severe blunt
thoracic and cervical trauma. In this case report we present a 24-year-old man
with pneumomediastinum due to blunt chest trauma after jumping from a bridge into
a river. He complained of persistent retrosternal pain with exacerbation during
deep inspiration. Physical examination showed only a slight tenderness of the
sternum and the extended Focused Assessment with Sonography for Trauma (e-FAST)
was normal. Pneumomediastinum was suspected by chest X-ray and confirmed by
computed tomography, which showed a lung contusion as probable cause of the
pneumomediastinum due to the "Mackling effect." Sonographic findings consistent
with pneumomediastinum, like the "air gap" sign, are helpful for quick bedside
diagnosis, but the diagnostic criteria are not yet as well established as for
pneumothorax. This present case shows that despite minimal findings in physical
examination and a normal e-FAST a pneumomediastinum is still possible in a
patient with chest pain after blunt chest trauma. Therefore, pneumomediastinum
should always be considered to prevent missing major aerodigestive injuries,
which can be associated with a high mortality rate.
PMID- 25114813
TI - Novel Mutation in the PKHD1 Gene Diagnosed Prenatally in a Fetus with Autosomal
Recessive Polycystic Kidney Disease.
AB - We report a 29-year-old gravida 2, para 0100, who presented at 19 weeks and 4
days of gestation for ultrasound to assess fetal anatomy. Routine midtrimester
fetal anatomy ultrasound revealed enlarged, hyperechoic fetal kidneys and normal
amniotic fluid index. Follow-up ultrasound at 23 weeks and 5 days revealed
persistently enlarged, hyperechoic fetal kidneys. Progressive oligohydramnios was
not evident until 29 weeks of gestation, with anhydramnios noted by 35 weeks of
gestation. Amniocentesis was performed for karyotype and to search for mutations
in the PKHD1 for the presumptive diagnosis of autosomal recessive polycystic
kidney disease (ARPKD). In our patient, a maternally inherited, previously
reported pathogenic missense mutation in the PKHD1 gene, c.10444C>T, was
identified. A second, previously unreported de novo mutation, c.5909-2delA, was
also identified. This mutation affects the canonical splice site and is most
likely pathogenic. Our case highlights PKHD1 allelic heterogeneity and the
importance of genetic testing in the prenatal setting where many other genetic
etiologies can phenocopy ARPKD.
PMID- 25114814
TI - Failure of Recombinant Activated Factor VII in Treatment of Diffuse Alveolar
Hemorrhage due to Cryoglobulinemic Vasculitis.
AB - Diffuse alveolar hemorrhage (DAH) is a serious complication of the small vessel
vasculitis syndromes and carries a high mortality. Recombinant activated factor
VII (rFVIIa) is used to treat bleeding in patients with hemophilia and antibodies
to factor VIII or IX. It is increasingly being used in life-threatening
hemorrhage in a variety of other settings in which conventional therapy is
unsuccessful. Randomized controlled trials of rFVIIa in DAH are lacking. However,
several case reports have described a complete or sustained control of DAH using
rFVIIa after patients failed to respond to medical treatment. There are no case
reports in the literature describing the use or the failure of rFVIIa in DAH
associated with cryoglobulinemic vasculitis. We here report the failure of rFVIIa
to control DAH in a patient with CD5+ B-cell non-Hodgkin's lymphoma and
cryoglobulinemic vasculitis.
PMID- 25114815
TI - Disseminated abdominal hydatidosis: a rare presentation of common infectious
disease.
AB - Hydatid disease is one of the most geographically widespread zoonoses with
substantial disease burden. In this report we are discussing an unusual case of
intra-abdominal HD that was ongoing for 22 years despite two surgical
interventions. Significant symptomatic relief was achieved within the first two
months of combination therapy with albendazole and praziquantel. HD is still of
public health concern in the Middle East that needs optimized care.
PMID- 25114816
TI - Chryseobacterium indologenes Septicemia in an Infant.
AB - Chryseobacterium indologenes is a rare cause of infection in children. The
organism causes infections mostly in hospitalised patients with severe underlying
diseases. The choice of an effective drug for the treatment of infections due to
C. indologenes is difficult as the organism has a limited spectrum of
antimicrobial sensitivity. We present a case of nosocomial septicemia caused by
C. indologenes in an infant with congenital heart disease who was successfully
treated with trimethoprim sulfamethoxazole and also reviewed fourteen additional
cases of C. indologenes infections reported in the English literature in this
report.
PMID- 25114817
TI - Subphrenic abscess as a complication of hemodialysis catheter-related infection.
AB - We describe an unusual case of subphrenic abscess complicating a central venous
catheter infection caused by Pseudomonas aeruginosa in a 59-year-old woman
undergoing hemodialysis. The diagnosis was made through computed tomography, and
Pseudomonas aeruginosa was isolated from the purulent drainage of the subphrenic
abscess, the catheter tip and exit site, and the blood culture samples. A
transesophageal echocardiography showed a large tubular thrombus in superior vena
cava, extending to the right atrium, but no evidence of endocarditis or other
metastatic infectious foci. Catheter removal, percutaneous abscess drainage,
anticoagulation, and antibiotics resulted in a favourable outcome.
PMID- 25114818
TI - Concurrent Malignant Solitary Fibrous Tumor Arising from the Omentum and Grade 3
Endometrial Endometrioid Adenocarcinoma of the Uterus with p53 Immunoreactivity.
AB - A malignant solitary fibrous tumor arising from the omentum is extremely rare. To
our knowledge, this is the first case of a malignant solitary fibrous omentum
tumor coexisting with uterine corpus cancer. A 62-year-old woman presented to our
hospital with vaginal discharge. Endometrioid adenocarcinoma was diagnosed by
endometrial curettage. In addition, a solid tumor in front of the uterus was
detected following computed tomography and/or magnetic resonance imaging, which
was suspected to be a primary (or secondary) malignant tumor arising from the
omentum. Hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and
lymphadenectomy were performed. A malignant solitary fibrous tumor of the omentum
and grade 3 endometrioid adenocarcinoma of the uterus were diagnosed by
pathohistological analysis. Interestingly, the tumor cells were immunoreactive
for p53. Adjuvant chemotherapy was administered for the uterine corpus cancer and
the patient remains healthy 48 months after the surgery. These tumors may have
become malignant due to the presence of p53 mutations.
PMID- 25114819
TI - Spontaneous Hemoperitoneum due to Rupture of Uterine Varicose Veins during Labor
Successfully Treated by Percutaneous Embolization.
AB - Hemoperitoneum during pregnancy is a rare but potentially lethal clinical
condition. Improvements in antenatal and intrapartum care, especially in surgical
and anesthetic techniques, have reduced maternal mortality; perinatal mortality
remains very high (31%). Treatment is based on the systemic correction of
hypovolemia and immediate surgery via laparotomy or laparoscopy in cases in the
first trimester of pregnancy for hemostatic purposes. Sometimes, hysterectomy is
needed. A 35-year-old Asiatic primigravid woman at 37 weeks' gestation with
otherwise uneventful pregnancy came to the hospital referring abrupt-onset lumbar
and abdominal pain. A bleeding uterine superficial varicocele of about 7 cm was
found on the left uterine horn during Caesarean section. Interventional
radiologic embolization of both uterine arteries was successfully performed.
Posterior evolution of the patient was favorable. Percutaneous vascular
embolization of the uterine arteries is an effective alternative treatment for
many obstetrical and gynecological causes of bleeding. The main advantage of this
technique is the low rate of serious complications and the preservation of
reproductive function. To our knowledge, this is the first case of spontaneous
intrapartum hemoperitoneum treated with this technique. An early diagnosis and a
rapid indication of this therapeutic option are essential. Hemodynamic stability
is needed to decide this conservative management.
PMID- 25114820
TI - Retracted: Intravenous leiomyoma with extension to the heart: a case report and
review of the literature.
PMID- 25114821
TI - Malignant mesenteric perivascular epithelioid cell neoplasm presenting as an
intra-abdominal fistula in a 49-year-old female.
AB - Perivascular epithelioid cell tumors are rare mesenchymal tumors arising from
histologically and immunohistochemically distinctive perivascular epithelioid
cells that express both myogenic and melanocytic markers. These tumors are known
to arise from different organs in the body and usually have an unpredictable
clinical course. We report a case of a 49-year-old female who presented with
diffuse abdominal pain, fever, chills, and nonbilious vomiting for a day. Work-up
revealed a mesenteric mass measuring 13.5 * 7.7 * 9.5 cm, arising in the
mesentery of the hepatic flexure, with adjacent gas suggestive of fistularization
into the right colon. An exploratory laparotomy with resection of the mesenteric
mass was performed, and the initial histopathology results were compatible with
either an adenocarcinoma or a sarcoma; however, because of poor differentiation
it was difficult to make a definitive diagnosis. However, final histopathology
results revealed a malignant perivascular epithelioid cell tumor (with
reservation that a S100 negative metastatic melanoma must be excluded
clinically). Following surgery the patient was started on everolimus, an m-TOR
inhibitor, and has shown good response to this medication.
PMID- 25114822
TI - Bioabsorbable suture anchor migration to the acromioclavicular joint: how far can
these implants go?
AB - Few complications regarding the use of bioabsorbable suture anchors in the
shoulder have been reported. What motivated this case report was the unusual
location of the anchor, found in the acromioclavicular joint which, to our
knowledge, has never been reported so far. A 53-year old male with previous
rotator cuff (RC) repair using bioabsorbable suture anchors presented with pain
and weakness after 2 years of surgery. A suspicion of retear of the RC led to
request of a magnetic resonance image, in which the implant was found located in
the acromioclavicular joint. The complications reported with the use of metallic
implants around the shoulder led to the development of bioabsorbable anchors.
Advantages are their absorption over time, minimizing the risk of migration or
interference with revision surgery, less artifacts with magnetic resonance
imaging, and tendon-to-bone repair strength similar to metallic anchors. Since
the use of bioabsorbable suture anchors is increasing, it is important to know
the possible complications associated with these devices.
PMID- 25114823
TI - Solitary fibrous tumor of the lumbar spine: the great mimicker-report of the
fifth case.
AB - Solitary fibrous tumor (SFT) is a rare neoplasm occurring in the central nervous
system. It rarely occurs in the spine. This paper reports the fifth case of SFT
in a 34-year-old female and focusses on differential diagnosis and importance of
surgical treatment.
PMID- 25114824
TI - Invasive mucinous adenocarcinoma associated with adjacent sessile serrated lesion
of the appendix vermiform: a case report.
AB - Although the definition of sessile serrated lesion (SSL) of colon is
controversial and the risk of progression to malignancy is also under
investigation at present, SSL is generally described as a polyp characterized by
a serrated architecture. It is estimated to represent a feature of a new
cancerization pathway, coined "serrated neoplasia pathway," particularly in right
sided colon adenocarcinomas. On the other hand, in appendix, the role of this
pathway remains uncertain, probably because very few cases of appendiceal
adenocarcinoma associated with SSL were reported, and furthermore,
immunohistochemical examination was rarely carried out. We herein report an
interesting case of invasive appendiceal mucinous adenocarcinoma exhibiting SSL,
which was pathologically estimated as a potential precursor lesion, and performed
representative immunohistochemistry for both the mucinous adenocarcinoma and SSL
in the same specimen. To further elucidate the progression of the appendiceal
carcinoma from SSL, both an adequate sectioning of the lesion and systematic
immunohistochemical examination of a large number of appendiceal carcinoma cases
containing adjacent SSL would be required.
PMID- 25114825
TI - Perilobar nephroblastomatosis: natural history and management.
AB - Nephroblastomatosis (NB) has been considered as a precursor of Wilms tumor (WT).
The natural history of NB seems to present significant variation as some lesions
may regress spontaneously, while others may grow and expand or relapse and
develop into WT later in childhood. Although, most investigators suggest adjutant
chemotherapy, the effect and duration of treatment are not well established.
Children with diffuse perilobar NB, Beckwith-Wiedemann syndrome, and
hemihypertrophy seem to particularly benefit from treatment. We discuss our
experience on two cases of NB and we review the literature for the management of
this rare condition.
PMID- 25114826
TI - Immunosuppressant-associated neurotoxicity responding to olanzapine.
AB - Immunosuppressants, particularly tacrolimus, can induce neurotoxicity in solid
organ transplantation cases. A lower clinical threshold to switch from tacrolimus
to another immunosuppressant agent has been a common approach to reverse this
neurotoxicity. However, immunosuppressant switch may place the graft at risk,
and, in some cases, continuation of the same treatment protocol may be necessary.
We report a case of immunosuppressant-associated neurotoxicity with prominent
neuropsychiatric manifestation and describe psychiatric intervention with
olanzapine that led to clinical improvement while continuing tacrolimus
maintenance.
PMID- 25114827
TI - Treatment of anxiety and depression in a patient with brugada syndrome.
AB - Background. Brugada syndrome is rare and has been a clinically diagnosable entity
since 1992. Its clinical manifestations are highly variable, and while some
patients remain asymptomatic, others endure sudden cardiac death. Initial
presenting symptoms may include palpitations, seizures, syncope, and nocturnal
agonal respiration. The diagnosis of Brugada syndrome relies on both clinical
findings and characteristic ECG patterns that occur spontaneously or are induced
by usage of sodium-channel blocking agents. Aims of Case Report. Many
psychiatrists may be unaware of the possibility of medical cocontributing
etiologies to physical symptoms of anxiety and depression. We present a case of a
patient who was treated psychiatrically for anxiety and panic attacks and who was
subsequently diagnosed with Brugada syndrome and treated medically with an
implantable cardioverter defibrillator (ICD), the only treatment option
demonstrated to be effective. Her psychiatric symptoms predated her diagnosis of
Brugada syndrome by at least fifteen years. Conclusion. The patient's eventual
diagnosis of Brugada syndrome altered the course of her psychopharmacologic
medication management and illustrates the utility of a psychosomatic approach to
psychiatric symptom management.
PMID- 25114828
TI - Response to rituximab in a case of lupus associated digital ischemia.
AB - We report the case of a 38-year-old female patient with systemic lupus
erythematosus (SLE) and Jaccoud arthritis (JA) that sequentially developed
digital ischemic lesions of the hands. In spite of follow-up treatment with
glucocorticoids, immunosuppressant, antiaggregant, and potent vasodilatator
agents, a serious progression to digital gangrene over a one-month period was
observed. Surprisingly, her nonhealing digital lesions improved after two cycles
of rituximab (RTX) administration.
PMID- 25114830
TI - Notch and TGFbeta: Functional partners facilitating tumor progression.
AB - Cell signals integral to the tumor microenvironment influence cancer progression.
Tumor-associated myeloid cells secrete pro-tumorigenic agents including, but not
limited to, the potent cytokine transforming growth factor beta (TGFbeta). We
have discovered a network of extrinsic signals including delta-like 4 (Dll4),
Notch and TGFbeta, linking malignant cells and tumor-infiltrating myeloid cells,
a nexus portending a clinically-relevant anticancer treatment.
PMID- 25114829
TI - The methodological quality of animal research in critical care: the public face
of science.
AB - BACKGROUND: Animal research (AR) findings often do not translate to humans; one
potential reason is the poor methodological quality of AR. We aimed to determine
this quality of AR reported in critical care journals. METHODS: All AR published
from January to June 2012 in three high-impact critical care journals were
reviewed. A case report form and instruction manual with clear definitions were
created, based on published recommendations, including the ARRIVE guidelines.
Data were analyzed with descriptive statistics. RESULTS: Seventy-seven AR
publications were reviewed. Our primary outcome (animal strain, sex, and weight
or age described) was reported in 52 (68%; 95% confidence interval, 56% to 77%).
Of the 77 publications, 47 (61%) reported randomization; of these, 3 (6%)
reported allocation concealment, and 1 (2%) the randomization procedure. Of the
77 publications, 31 (40%) reported some type of blinding; of these, disease
induction (2, 7%), intervention (7, 23%), and/or subjective outcomes (17, 55%)
were blinded. A sample size calculation was reported in 4/77 (5%). Animal numbers
were missing in the Methods section in 16 (21%) publications; when stated, the
median was 32 (range 6 to 320; interquartile range, 21 to 70). Extra animals used
were mentioned in the Results section in 31 (40%) publications; this number was
unclear in 23 (74%), and >100 for 12 (16%). When reporting most outcomes, numbers
with denominators were given in 35 (45%), with no unaccounted numbers in 24
(31%), and no animals excluded from analysis in 20 (26%). Most (49, 64%) studies
reported >40, and another 19 (25%) reported 21 to 40 statistical comparisons.
Internal validity limitations were discussed in 7 (9%), and external validity (to
humans) discussed in 71 (92%), most with no (30, 42%) or only a vague (9, 13%)
limitation to this external validity mentioned. CONCLUSIONS: The reported
methodological quality of AR was poor. Unless the quality of AR significantly
improves, the practice may be in serious jeopardy of losing public support.
PMID- 25114831
TI - Tumor-associated autoantibodies correlate with poor outcome in prostate cancer
patients treated with androgen deprivation and external beam radiation therapy.
AB - Standard cancer treatments trigger immune responses that may influence tumor
control. The nature of these responses varies depending on the tumor and the
treatment modality. We previously reported that radiation and androgen
deprivation therapy (ADT) induce tumor-associated autoantibody responses in
prostate cancer patients. This follow-up analysis was conducted to assess the
relationship between autoantibody responses and clinical outcome. Patients with
non-metastatic prostate cancer received external beam radiation therapy (EBRT)
plus neoadjuvant and concurrent androgen deprivation. Treatment-induced
autoantibodies were detected in almost a third of patients receiving
combinatorial ADT and EBRT. Unexpectedly, patients that developed autoantibody
responses to tumor antigens had a significantly lower 5-year biochemical failure
free survival (BFFS) than patients that did not develop an autoantibody response.
Thus, tumor-reactive autoantibodies may be associated with increased risk of
biochemical failure and immunomodulation to prevent autoantibody development may
improve BFFS for select, high-risk prostate cancer patients receiving both ADT
and EBRT.
PMID- 25114833
TI - Targeting COX-2 abrogates mammary tumorigenesis: Breaking cancer-associated
suppression of immunosurveillance.
AB - Three studies addressed the role of cyclooxygenase-2 (COX-2) in mammary
tumorigenesis using epithelial and macrophage COX-2 knockout mice. Deletion of
COX-2 in either cell restored, at least partially, tumor immunosurveillance
either by changing macrophage function to offset pro-tumor effects, or by
attracting more cytotoxic T lymphocytes and natural killer cells to the tumor.
These studies suggest benefits from targeted COX-2 selective inhibition in
combination with immunotherapies.
PMID- 25114832
TI - STING-dependent cytosolic DNA sensor pathways regulate NKG2D ligand expression.
AB - The DNA damage response (DDR) upregulates the expression of NKG2D ligands
(NKG2DLs).1,2 We have recently reported that the DDR also induces the presence of
cytosolic DNA in B-cell lymphoma cells, which leads to the activation of STING
dependent cytosolic DNA sensor pathways and the expression of RAE-1 ligands for
NKG2D.3.
PMID- 25114834
TI - Linking tumor hypoxia with VEGFR2 signaling and compensatory angiogenesis:
Glycans make the difference.
AB - Although blocking vascular endothelial growth factor (VEGF) signaling is
clinically beneficial in certain cancers, tumor regrowth in treated patients
suggests that compensatory angiogenic programs may limit the efficacy of anti
VEGF treatment. We found that association of galectin-1 with complex N-glycans on
VEGFR2 links tumor hypoxia to VEGFR2 signaling and preserves angiogenesis in
response to VEGF blockade.
PMID- 25114835
TI - The fatal alliance of cancer and T cells: How pancreatic tumor cells gather
immunosuppressive T cells.
AB - Immune evasion is a hallmark of cancer. We recently identified the adhesion
molecule L1CAM as biomarker of pancreatic ductal adenocarcinoma (PDAC) associated
with poor prognosis. During inflammation-associated carcinogenesis, L1CAM drives
the enrichment of highly immunosuppressive CD4+CD25-CD69+ T cells. Thus, L1CAM
may serve as a target in immunomodulatory therapy for PDAC.
PMID- 25114836
TI - Adaptation and fatigue model for neuron networks and large time asymptotics in a
nonlinear fragmentation equation.
AB - Motivated by a model for neural networks with adaptation and fatigue, we study a
conservative fragmentation equation that describes the density probability of
neurons with an elapsed time s after its last discharge. In the linear setting,
we extend an argument by Laurencot and Perthame to prove exponential decay to the
steady state. This extension allows us to handle coefficients that have a large
variation rather than constant coefficients. In another extension of the
argument, we treat a weakly nonlinear case and prove total desynchronization in
the network. For greater nonlinearities, we present a numerical study of the
impact of the fragmentation term on the appearance of synchronization of neurons
in the network using two "extreme" cases. Mathematics Subject Classification
(2000)2010: 35B40, 35F20, 35R09, 92B20.
PMID- 25114838
TI - Towards optimal treatment of ductal carcinoma in situ.
AB - Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast
cancer with a variable biological behavior which is difficult to accurately
predict using the current clinico-pathological parameters. Randomized controlled
trials have demonstrated that adjuvant radiotherapy (RT) reduces the risk of
local recurrence after adequate local excision of DCIS. Tamoxifen may be
considered as an adjuvant endocrine treatment in patients with high risk estrogen
receptor positive disease. There is however a growing consensus that RT can be
safely omitted in a subgroup of patients with favorable biological features in
order to avoid overtreatment. The sentinel node biopsy is not routinely indicated
but should be considered in women undergoing mastectomy for DCIS. The discovery
of molecular signatures that accurately predict the biological behavior of this
common malignancy will facilitate a personalized treatment approach in the
future.
PMID- 25114837
TI - Free radical derivatives formed from cyclooxygenase-catalyzed dihomo-gamma
linolenic acid peroxidation can attenuate colon cancer cell growth and enhance 5
fluorouracil's cytotoxicity.
AB - Dihomo-gamma-linolenic acid (DGLA) and its downstream fatty acid arachidonic acid
(AA) are both nutritionally important omega-6 polyunsaturated fatty acids (omega
6s). Evidence shows that, via COX-mediated peroxidation, DGLA and its metabolites
(1-series prostaglandins) are associated with anti-tumor activity, while AA and
its metabolites (2-series prostaglandins) could be tightly implicated in various
cancer diseases. However, it still remains a mystery why DGLA and AA possess
contrasting bioactivities. Our previous studies showed that DGLA could go through
an exclusive C-8 oxygenation pathway during COX-catalyzed lipid peroxidation in
addition to a C-15 oxygenation pathway shared by both DGLA and AA, and that the
exclusive C-8 oxygenation could lead to the production of distinct DGLA's free
radical derivatives that may be correlated with DGLA's anti-proliferation
activity. In the present work, we further investigate the anti-cancer effect of
DGLA's free radical derivatives and their associated molecular mechanisms. Our
study shows that the exclusive DGLA's free radical derivatives from C-8
oxygenation lead to cell growth inhibition, cell cycle arrest and apoptosis in
the human colon cancer cell line HCA-7 colony 29, probably by up-regulating the
cancer suppressor p53 and the cell cycle inhibitor p27. In addition, these
exclusive radical derivatives were also able to enhance the efficacy of 5
Fluorouracil (5-FU), a widely used chemo-drug for colon cancer. For the first
time, we show how DGLA's radical pathway and metabolites are associated with
DGLA's anti-cancer activities and able to sensitize colon cancer cells to chemo
drugs such as 5-FU. Our findings could be used to guide future development of a
combined chemotherapy and dietary care strategy for colon cancer treatment.
PMID- 25114841
TI - Breast cancer-related lymphedema: Symptoms, diagnosis, risk reduction, and
management.
AB - The global burden of breast cancer continues to increase largely because of the
aging and growth of the world population. More than 1.38 million women worldwide
were estimated to be diagnosed with breast cancer in 2008, accounting for 23% of
all diagnosed cancers in women. Given that the 5-year survival rate for breast
cancer is now 90%, experiencing breast cancer is ultimately about quality of
life. Women treated for breast cancer are facing a life-time risk of developing
lymphedema, a chronic condition that occurs in up to 40% of this population and
negatively affects breast cancer survivors' quality of life. This review offers
an insightful understanding of the condition by providing clinically relevant and
evidence based knowledge regarding lymphedema symptoms, diagnosis, risk
reduction, and management with the intent to inform health care professionals so
that they might be better equipped to care for patients.
PMID- 25114840
TI - Targeting autophagy in breast cancer.
AB - Macroautophagy (referred to as autophagy here) is an intracellular degradation
pathway enhanced in response to a variety of stresses and in response to nutrient
deprivation. This process provides the cell with nutrients and energy by
degrading aggregated and damaged proteins as well as compromised organelles.
Since autophagy has been linked to diverse diseases including cancer, it has
recently become a very interesting target in breast cancer treatment. Indeed,
current clinical trials are trying to use chloroquine or hydroxychloroquine,
alone or in combination with other drugs to inhibit autophagy during breast
cancer therapy since chemotherapy and radiation, regimens that are used to treat
breast cancer, are known to induce autophagy in cancer cells. Importantly, in
breast cancer, autophagy has been involved in the development of resistance to
chemotherapy and to anti-estrogens. Moreover, a close relationship has recently
been described between autophagy and the HER2 receptor. Here, we discuss some of
the recent findings relating autophagy and cancer with a particular focus on
breast cancer therapy.
PMID- 25114843
TI - Diagnosis and surgical management of breast cancer metastatic to the spine.
AB - Breast cancer is the most common malignancy and the second leading cause of death
in Western women. Breast cancer most commonly metastasizes to the bone and has a
particular affinity with the spine, accounting for 2/3 of osseous metastases
discovered. With significant improvements in cancer therapies, the number of
patients at risk for symptomatic spinal metastases is likely to increase.
Patients may suffer from intractable pain and neurological dysfunction,
negatively influencing their quality of life. Timely diagnosis of patients is
crucial and has been aided by several breakthrough advances in imaging techniques
which aid in detection, staging, and follow-up of bone metastases. Breast
metastases are usually responsive to hormonal therapy and pharmacologic
interventions, but skeletal metastases often require surgical intervention. The
treatments are palliative but goals include the preserving or restoring
neurologic function, ensuring spinal stability, and relieving pain. Advances in
surgical techniques and instrumentation have allowed more effective decompression
and stabilization of the spine, and with the support of recent evidence the trend
has shifted towards using more advanced surgical options in appropriately
selected patients. In this review, the clinical presentation, diagnosis, patient
selection, and surgical management of breast cancer metastatic to the spine are
discussed.
PMID- 25114842
TI - Mechanisms and therapeutic advances in the management of endocrine-resistant
breast cancer.
AB - The estrogen receptor (ER) pathway plays a critical role in breast cancer
development and progression. Endocrine therapy targeting estrogen action is the
most important systemic therapy for ER positive breast cancer. However its
efficacy is limited by intrinsic and acquired resistance. Mechanisms responsible
for endocrine resistance include deregulation of the ER pathway itself, including
loss of ER expression, post-translational modification of ER, deregulation of ER
co-activators; increased receptor tyrosine kinase signaling leading to activation
of various intracellular pathways involved in signal transduction, proliferation
and cell survival, including growth factor receptor tyrosine kinases human
epidermal growth factor receptor-2, epidermal growth factor receptor,
PI3K/AKT/mammalian target of rapamycin (mTOR), Mitogen activated kinase
(MAPK)/ERK, fibroblast growth factor receptor, insulin-like growth factor-1
receptor; alterations in cell cycle and apoptotic machinery; Epigenetic
modification including dysregulation of DNA methylation, histone modification,
and nucleosome remodeling; and altered expression of specific microRNAs.
Functional genomics has helped us identify a catalog of genetic and epigenetic
alterations that may be exploited as potential therapeutic targets and biomarkers
of response. New treatment combinations targeting ER and such oncogenic signaling
pathways which block the crosstalk between these pathways have been proven
effective in preclinical models. Results of recent clinical studies suggest that
subsets of patients benefit from the combination of inhibitor targeting certain
oncogenic signaling pathway with endocrine therapy. Especially, inhibition of the
mTOR signaling pathway, a key component implicated in mediating multiple
signaling cascades, offers a promising approach to restore sensitivity to
endocrine therapy in breast cancer. We systematically reviewed important
publications cited in PubMed, recent abstracts from ASCO annual meetings and San
Antonio Breast Cancer Symposium, and relevant trials registered at
ClinicalTrials.gov. We present the molecular mechanisms contributing to endocrine
resistance, in particular focusing on the biological rationale for the clinical
development of novel targeted agents in endocrine resistant breast cancer. We
summarize clinical trials utilizing novel strategies to overcome therapeutic
resistance, highlighting the need to better identify the appropriate patients
whose diseases are most likely to benefit from these specific strategies.
PMID- 25114844
TI - Weight gain following breast cancer diagnosis: Implication and proposed
mechanisms.
AB - Weight gain occurs in the majority of women following breast cancer treatment. An
overview of studies describing weight gain amongst women treated with early to
modern chemotherapy regimens is included. Populations at higher risk include
women who are younger, closer to ideal body weight and who have been treated with
chemotherapy. Weight gain ranges between 1 to 5 kg, and may be associated with
change in body composition with gain in fat mass and loss in lean body mass.
Women are unlikely to return to pre-diagnosis weight. Possible mechanisms
including inactivity and metabolic changes are explored. Potential interventions
are reviewed including exercise, dietary changes and pharmacologic agents.
Although breast cancer prognosis does not appear to be significantly impacted,
weight gain has negative consequences on quality of life and overall health.
Future studies should explore change in body composition, metabolism and insulin
resistance. Avoiding weight gain in breast cancer survivors following initial
diagnosis and treatment should be encouraged.
PMID- 25114839
TI - Paraneoplastic syndromes associated with lung cancer.
AB - Paraneoplastic syndromes are signs or symptoms that occur as a result of organ or
tissue damage at locations remote from the site of the primary tumor or
metastases. Paraneoplastic syndromes associated with lung cancer can impair
various organ functions and include neurologic, endocrine, dermatologic,
rheumatologic, hematologic, and ophthalmological syndromes, as well as
glomerulopathy and coagulopathy (Trousseau's syndrome). The histological type of
lung cancer is generally dependent on the associated syndrome, the two most
common of which are humoral hypercalcemia of malignancy in squamous cell
carcinoma and the syndrome of inappropriate antidiuretic hormone secretion in
small cell lung cancer. The symptoms often precede the diagnosis of the
associated lung cancer, especially when the symptoms are neurologic or
dermatologic. The proposed mechanisms of paraneoplastic processes include the
aberrant release of humoral mediators, such as hormones and hormone-like
peptides, cytokines, and antibodies. Treating the underlying cancer is generally
the most effective therapy for paraneoplastic syndromes, and treatment soon after
symptom onset appears to offer the best potential for symptom improvement. In
this article, we review the diagnosis, potential mechanisms, and treatments of a
wide variety of paraneoplastic syndromes associated with lung cancer.
PMID- 25114845
TI - Pathogenesis, prevention, diagnosis and treatment of breast cancer.
AB - Breast cancer is the most common cancer affecting women worldwide. Prediction
models stratify a woman's risk for developing cancer and can guide screening
recommendations based on the presence of known and quantifiable hormonal,
environmental, personal, or genetic risk factors. Mammography remains the
mainstay breast cancer screening and detection but magnetic resonance imaging and
ultrasound have become useful diagnostic adjuncts in select patient populations.
The management of breast cancer has seen much refinement with increased
specialization and collaboration with multidisciplinary teams that include
surgeons, oncologists, radiation oncologists, nurses, geneticist, reconstructive
surgeons and patients. Evidence supports a less invasive surgical approach to the
staging and management of the axilla in select patients. In the era of
patient/tumor specific management, the advent of molecular and genomic profiling
is a paradigm shift in the treatment of a biologically heterogenous disease.
PMID- 25114846
TI - Evolution of breast cancer therapeutics: Breast tumour kinase's role in breast
cancer and hope for breast tumour kinase targeted therapy.
AB - There have been significant improvements in the detection and treatment of breast
cancer in recent decades. However, there is still a need to develop more
effective therapeutic techniques that are patient specific with reduced toxicity
leading to further increases in patients' overall survival; the ongoing progress
in understanding recurrence, resistant and spread also needs to be maintained.
Better understanding of breast cancer pathology, molecular biology and
progression as well as identification of some of the underlying factors involved
in breast cancer tumourgenesis and metastasis has led to the identification of
novel therapeutic targets. Over a number of years interest has risen in breast
tumour kinase (Brk) also known as protein tyrosine kinase 6; the research field
has grown and Brk has been described as a desirable therapeutic target in
relation to tyrosine kinase inhibition as well as disruption of its kinase
independent activity. This review will outline the current "state of play" with
respect to targeted therapy for breast cancer, as well as discussing Brk's role
in the processes underlying tumour development and metastasis and its potential
as a therapeutic target in breast cancer.
PMID- 25114847
TI - Epithelial-mesenchymal transition transcription factors and miRNAs: "Plastic
surgeons" of breast cancer.
AB - Growing evidence suggests that breast cancer cell plasticity arises due to a
partial reactivation of epithelial-mesenchymal transition (EMT) programs in order
to give cells pluripotency, leading to a stemness-like phenotype. A complete EMT
would be a dead end program that would render cells unable to fully metastasize
to distant organs. Evoking the EMT-mesenchymal-to-epithelial transition (MET)
cascade promotes successful colonization of distal target tissues. It is unlikely
that direct reprogramming or trans-differentiation without passing through a
pluripotent stage would be the preferred mechanism during tumor progression. This
review focuses on key EMT transcriptional regulators, EMT-transcription factors
involved in EMT (TFs) and the miRNA pathway, which are deregulated in breast
cancer, and discusses their implications in cancer cell plasticity. Cross
regulation between EMT-TFs and miRNAs, where miRNAs act as co-repressors or co
activators, appears to be a pivotal mechanism for breast cancer cells to acquire
a stem cell-like state, which is implicated both in breast metastases and tumor
recurrence. As a master regulator of miRNA biogenesis, the ribonuclease type III
endonuclease Dicer plays a central role in EMT-TFs/miRNAs regulating networks.
All these EMT-MET key regulators represent valuable new prognostic and predictive
markers for breast cancer as well as promising new targets for drug-resistant
breast cancers.
PMID- 25114848
TI - Regulation of the mRNA half-life in breast cancer.
AB - The control of the half-life of mRNA plays a central role in normal development
and in disease progression. Several pathological conditions, such as breast
cancer, correlate with deregulation of the half-life of mRNA encoding growth
factors, oncogenes, cell cycle regulators and inflammatory cytokines that
participate in cancer. Substantial stability means that a mRNA will be available
for translation for a longer time, resulting in high levels of protein gene
products, which may lead to prolonged responses that subsequently result in over
production of cellular mediators that participate in cancer. The stability of
these mRNA is regulated at the 3'UTR level by different mechanisms involving mRNA
binding proteins, micro-RNA, long non-coding RNA and alternative polyadenylation.
All these events are tightly inter-connected to each other and lead to steady
state levels of target mRNAs. Compelling evidence also suggests that both mRNA
binding proteins and regulatory RNAs which participate to mRNA half-life
regulation may be useful prognostic markers in breast cancers, pointing to a
potential therapeutic approach to treatment of patients with these tumors. In
this review, we summarize the main mechanisms involved in the regulation of mRNA
decay and discuss the possibility of its implication in breast cancer
aggressiveness and the efficacy of targeted therapy.
PMID- 25114849
TI - Molecular pathogenesis of bone metastases in breast cancer: Proven and emerging
therapeutic targets.
AB - Metastatic occurrence is the principal cause of death in breast cancer patients.
The high osteotropism makes breast cancer the most common primary tumor type
associated with metastatic bone disease. The peculiar clinical aspects associated
with metastases limited to the skeletal system suggest considering these cases as
a distinctive subset of metastatic patients with a better prognosis. Because bone
is frequently the first metastatic site in disease relapse, it is feasible that
the next improvement in therapeutic options for bone metastatic disease could be
associated with an improvement of survival expectation and quality of life in
breast cancer patients. Study of the molecular basis of bone remodeling and
breast cancer osteotropism has allowed identification of several therapeutic
candidates involved in formation and progression of bone metastases. These
targets are frequently the determinants of positive feedback between the tumor
and bone cells whose clinical outcome is osteolytic lesions. In this review, we
discuss the physiopathologic features underlying targeted therapeutic strategies
aimed at interfering with the aberrant bone remodeling associated with breast
cancer metastases.
PMID- 25114850
TI - Effects of psoralens as anti-tumoral agents in breast cancer cells.
AB - This review examines the biological properties of coumarins, widely distributed
at the highest levels in the fruit, followed by the roots, stems and leaves, by
considering their beneficial effects in the prevention of some diseases and as
anti-cancer agents. These compounds are well known photosensitizing drugs which
have been used as pharmaceuticals for a broad number of therapeutic applications
requiring cell division inhibitors. Despite this, even in the absence of
ultraviolet rays they are active. The current paper mainly focuses on the effects
of psoralens on human breast cancer as they are able to influence many aspects of
cell behavior, such as cell growth, survival and apoptosis. In addition,
analytical and pharmacological data have demonstrated that psoralens antagonize
some metabolizing enzymes, affect estrogen receptor stability and counteract cell
invasiveness as well as cancer drug resistance. The scientific findings
summarized highlight the pleiotropic functions of phytochemical drugs, given that
recently their target signals and how these are modified in the cells have been
identified. The encouraging results in this field suggest that multiple
modulating strategies based on coumarin drugs in combination with canonical
chemotherapeutic agents or radiotherapy could be a useful approach to address the
treatment of many types of cancer.
PMID- 25114852
TI - Impact of CYP2D*6 in the adjuvant treatment of breast cancer patients with
tamoxifen.
AB - Biotransformation of tamoxifen to the potent antiestrogen endoxifen is performed
by cytochrome P450 (CYP) enzymes, in particular the CYP2D6 isoform. CYP2D6*4 is
one of the most frequent alleles associated with loss of enzymatic activity. The
incidence of CYP2D6*4 among Caucasians is estimated up to 27%, while it is
present in up to 90% of all poor metabolizers within the Caucasian population.
The hypothesis under question is whether the presence of one or two non
functioning (null) alleles predicts an inferior outcome in postmenopausal women
with breast cancer receiving adjuvant treatment with tamoxifen. The numerous
existing studies investigating the association of CYP2D6 with treatment failure
in breast cancer are inconsistent and give rather conflicting results. Currently,
routine CYP2D6 testing among women with breast cancer is not recommended and the
significance of CYP2D6 phenotype in decision making regarding the administration
of tamoxifen is unclear. The present study summarizes current literature
regarding clinical studies on CYP2D6*4, particularly in terms of response to
tamoxifen therapy and breast cancer outcome.
PMID- 25114851
TI - Main controversies in breast cancer.
AB - In this article, we have reviewed available evidence for diagnosis, treatment,
and follow-up in female breast cancer (BC). Into daily clinical practice some
controversies are occurred. Especially, in the diagnosis field, despite the fact
that the optimal age in which screening mammography should start is a subject of
intense controversy, there is a shift toward the beginning at the age of 40
although it is suggested that the net benefit is small for women aged 40 to 49
years. In addition, a promising tool in BC screening seems to be breast
tomosynthesis. Other tools such as 3D ultrasound and shear wave elastography
(SWE) are full of optimism in BC screening although ultrasonography is not yet a
first-line screening method and there is insufficient evidence to recommend the
systemic use of the SWE for BC screening. As for breast magnetic resonance
imaging (MRI), even if it is useful in BC detection in women who have a strong
family history of BC, it is not generally recommended as a screening tool.
Moreover, based on the lack of randomized clinical trials showing a benefit of
presurgical breast MRI in overall survival, it's integration into breast surgical
operations remains debatable. Interestingly, in contrast to fine needle
aspiration, core biopsy has gained popularity in presurgical diagnosis.
Furthermore, after conservative surgery in patients with positive sentinel lymph
nodes, the recent tendency is the shift from axillary dissection to axillary
conserving strategies. While the accuracy of sentinel lymph node after
neoadjuvant chemotherapy and second BC surgery remains controversial, more time
is needed for evaluation and for determining the optimal interval between the two
surgeries. Additionally, in the decision between immediate or delayed breast
reconstruction, there is a tendency in the immediate use. In the prevention of
BC, the controversial issue between tamoxifen and raloxifene becomes clear with
raloxifene be more profitable through the toxicities of tamoxifen. However, the
prevention of bone metastasis with bisphosphonates is still conflicting. Last but
not least, in the follow-up of BC survivors, mammography, history and physical
examination are the means of an early detection of BC recurrence. ed.
PMID- 25114853
TI - Significance of immunohistochemistry in breast cancer.
AB - The biological characteristics of the tumour are used to estimate prognosis and
select appropriate systemic therapy for patients with (breast) cancer. The advent
of molecular technology has incorporated new biomarkers along with
immunohistochemical and serum biomarkers. Immunohistochemical markers are often
used to guide treatment decisions, to classify breast cancer into subtypes that
are biologically distinct and behave differently, and both as prognostic and
predictive factors. Steroid hormone receptors, markers of tumour proliferation,
and factors involved in angiogenesis and apoptosis are of scientific interest. In
this review we will provide information on the immunohistochemical markers used
in the management of breast cancer patients using available data from the
literature. We consider the utility of established immunohistochemical markers,
and discuss the challenges involved in integrating novel molecular markers into
clinical practice.
PMID- 25114854
TI - Toremifene in the treatment of breast cancer.
AB - Although more widespread screening and routine adjuvant therapy has improved the
outcome for breast cancer patients in recent years, there remains considerable
scope for improving the efficacy, safety and tolerability of adjuvant therapy in
the early stage disease and the treatment of advanced disease. Toremifene is a
selective estrogen receptor modifier (SERM) that has been widely used for decades
in hormone receptor positive breast cancer both in early and late stage disease.
Its efficacy has been well established in nine prospective randomized phase III
trials compared to tamoxifen involving more than 5500 patients, as well as in
several large uncontrolled and non-randomized studies. Although most studies show
therapeutic equivalence between the two SERMs, some show an advantage for
toremifene. Several meta-analyses have also confirmed that the efficacy of
toremifene is at least as good as that of tamoxifen. In terms of safety and
tolerability toremifene is broadly similar to tamoxifen although there is some
evidence that toremifene is less likely to cause uterine neoplasms, serious
vascular events and it has a more positive effect on serum lipids than does
tamoxifen. Toremifene is therefore effective and safe in the treatment of breast
cancer. It provides not only a useful therapeutic alternative to tamoxifen, but
may bring specific benefits.
PMID- 25114855
TI - Exercise in patients coping with breast cancer: An overview.
AB - Breast cancer is the most common type of cancer in women, but fortunately has
high survival rates. Many studies have been performed to investigate the effects
of exercise in patients diagnosed with breast cancer. There is evidence that
exercise after the diagnosis of breast cancer improves mortality, morbidity,
health related quality of life, fatigue, physical functioning, muscle strength,
and emotional wellbeing. Based on scientific data, breast cancer patients should
be recommended to participate in rehabilitation programs including aerobic and
strength training. The aim of this article is to review the recently published
data on the effect of exercise in patients with breast cancer in order to present
the current perspective on the topic.
PMID- 25114856
TI - Biological subtypes of breast cancer: Prognostic and therapeutic implications.
AB - Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes
with distinct biological features that lead to differences in response patterns
to various treatment modalities and clinical outcomes. Traditional classification
systems regarding biological characteristics may have limitations for patient
tailored treatment strategies. Tumors with similar clinical and pathological
presentations may have different behaviors. Analyses of breast cancer with new
molecular techniques now hold promise for the development of more accurate tests
for the prediction of recurrence. Gene signatures have been developed as
predictors of response to therapy and protein gene products that have direct
roles in driving the biology and clinical behavior of cancer cells are potential
targets for the development of novel therapeutics. The present review summarizes
current knowledge in breast cancer molecular biology, focusing on novel
prognostic and predictive factors.
PMID- 25114857
TI - Current role of modern radiotherapy techniques in the management of breast
cancer.
AB - Breast cancer is the most common type of malignancy in females. Advances in
systemic therapies and radiotherapy (RT) provided long survival rates in breast
cancer patients. RT has a major role in the management of breast cancer. During
the past 15 years several developments took place in the field of imaging and
irradiation techniques, intensity modulated RT, hypofractionation and partial
breast irradiation. Currently, improvements in the RT technology allow us a
subsequent decrease in the treatment-related complications such as fibrosis and
long-term cardiac toxicity while improving the loco-regional control rates and
cosmetic results. Thus, it is crucial that modern radiotherapy techniques should
be carried out with maximum care and efficiency. Several randomized trials
provided evidence for the feasibility of modern radiotherapy techniques in the
management of breast cancer. However, the role of modern radiotherapy techniques
in the management of breast cancer will continue to be defined by the mature
results of randomized trials. Current review will provide an up-to-date evidence
based data on the role of modern radiotherapy techniques in the management of
breast cancer.
PMID- 25114858
TI - Therapeutic options for HER-2 positive breast cancer: Perspectives and future
directions.
AB - During the last 15 years we have witnessed an unprecedented expansion in the
drugs developed to target human epidermal growth factor receptor-2 (HER-2)
positive breast cancer. Trastuzumab, pertuzumab, ado-trastuzumab emtansine and
lapatinib are currently food and drug administration (FDA)-approved for the
treatment of breast cancer patients with HER-2 over-expressed. However, given the
amount of information gathered from years of uninterrupted clinical research, it
is essential to have periodic updates that succinctly recapitulate what we have
learnt over these last years and help us to apply that information in our daily
practice. This review will pursue that objective. We will summarize the most
relevant and updated information related to the state of the art management of
HER-2 positive breast cancer in all the clinical scenarios including the
adjuvant, neoadjuvant and metastatic settings. But we will also critically
appraise that literature in order to highlight some key clinical concepts that
should not be overlooked. Lastly, this review will also point out some of the
most promising strategies that are currently being tested and may soon become
available.
PMID- 25114859
TI - Modification in the diet can induce beneficial effects against breast cancer.
AB - The population tends to consume foods that in addition to their nutritional
values can offer some benefits to their health. There are many epidemiological
evidences and research studies in animal models suggesting that diet plays an
important role in breast cancer prevention or progression. This review summarized
some of the relevant researches about nutrition and cancer during the last years,
especially in breast cancer. The analysis of probiotics and fermented products
containing lactic acid bacteria in cancer prevention and/or treatment was
especially discussed. It was observed that a balance of fatty acids similar to
those of traditional Mediterranean diet, the consumption of fruits and
vegetables, dietary fiber intake, vitamin supplementation are, along with the
intake of probiotic products, the most extensively studied by the negative
association to breast cancer risk. The consumption of probiotics and fermented
products containing lactic acid bacteria was associated to reduce breast cancer
risk in some epidemiological studies. The use of animal models showed the
modulation of the host's immune response as one of the important effects
associated to the benefices observed with most probiotics. However; future assays
in human are very important before the medical community can accept the addition
of probiotic or fermented milks containing lactic acid bacteria as supplements
for cancer patients.
PMID- 25114860
TI - Challenges to the early diagnosis and treatment of breast cancer in developing
countries.
AB - This critical review of the literature assembles and compares available data on
breast cancer clinical stage, time intervals to care, and access barriers in
different countries. It provides evidence that while more than 70% of breast
cancer patients in most high-income countries are diagnosed in stages I and II,
only 20%-50% patients in the majority of low- and middle-income countries are
diagnosed in these earlier stages. Most studies in the developed world show an
association between an advanced clinical stage of breast cancer and delays
greater than three months between symptom discovery and treatment start. The
evidence assembled in this review shows that the median of this interval is 30-48
d in high-income countries but 3-8 mo in low- and middle-income countries. The
longest delays occur between the first medical consultation and the beginning of
treatment, known as the provider interval. The little available evidence suggests
that access barriers and quality deficiencies in cancer care are determinants of
provider delay in low- and middle-income countries. Research on specific access
barriers and deficiencies in quality of care for the early diagnosis and
treatment of breast cancer is practically non-existent in these countries, where
it is the most needed for the design of cost-effective public policies that
strengthen health systems to tackle this expensive and deadly disease.
PMID- 25114861
TI - Immediate nipple-areola-sparing mastectomy reconstruction: An update on
oncological and reconstruction techniques.
AB - Nipple-sparing mastectomy (NSM) is a safe technique in patients who are
candidates for conservation breast surgery. However, there is worry concerning
its oncological safety and surgical outcome in terms of postoperative
complications. The authors reviewed the literature to evaluate the oncological
safety, patient selection, surgical techniques, and also to identify the factors
influencing postoperative outcome and complication rates. Patient selection and
safety related to NSM are based on oncological and anatomical parameters. Among
the main criteria, the oncological aspects include the clinical stage of breast
cancer, tumor characteristics and location including small, peripherally located
tumors, without multicentricity, or for prophylactic mastectomy. Surgical success
depends on coordinated planning with the oncological surgeon and careful
preoperative and intraoperative management. In general, the NSM reconstruction is
related to autologous and alloplastic techniques and sometimes include contra
lateral breast surgery. Choice of reconstructive technique following NSM requires
accurate consideration of various patient related factors, including: breast
volume, degree of ptosis, areola size, clinical factors, and surgeon's
experience. In addition, tumor related factors include dimension, location and
proximity to the nipple-areola complex. Regardless of the fact that there is no
unanimity concerning the appropriate technique, the criteria are determined by
the surgeon's experience and the anatomical aspects of the breast. The positive
aspects of the technique utilized should include low interference with the
oncological treatment, reproducibility, and long-term results. Selected patients
can have safe outcomes and therefore this may be a feasible option for early
breast cancer management. However, available data demonstrates that NSM can be
safely performed for breast cancer treatment in selected cases. Additional
studies and longer follow-up are necessary to define consistent selection
criteria for NSM.
PMID- 25114862
TI - Pattern response of dendritic cells in the tumor microenvironment and breast
cancer.
AB - Breast cancer (BC) is the most common malignant neoplasm and the cause of death
by cancer among women worldwide. Its development, including malignancy grade and
patient prognosis, is influenced by various mutations that occur in the tumor
cell and by the immune system's status, which has a direct influence on the tumor
microenvironment and, consequently, on interactions with non-tumor cells involved
in the immunological response. Among the immune response cells, dendritic cells
(DCs) play a key role in the induction and maintenance of anti-tumor responses
owing to their unique abilities for antigen cross-presentation and promotion of
the activation of specific lymphocytes that target neoplasic cells. However, the
tumor microenvironment can polarize DCs, transforming them into immunosuppressive
regulatory DCs, a tolerogenic phenotype which limits the activity of effector T
cells and supports tumor growth and progression. Various factors and signaling
pathways have been implicated in the immunosuppressive functioning of DCs in
cancer, and researchers are working on resolving processes that can circumvent
tumor escape and developing viable therapeutic interventions to prevent or
reverse the expression of immunosuppressive DCs in the tumor microenvironment. A
better understanding of the pattern of DC response in patients with BC is
fundamental to the development of specific therapeutic approaches to enable DCs
to function properly. Various studies examining DCs immunotherapy have
demonstrated its great potential for inducing immune responses to specific
antigens and thereby reversing immunosuppression and related to clinical response
in patients with BC. DC-based immunotherapy research has led to immense
scientific advances, both in our understanding of the anti-tumor immune response
and for the treatment of these patients.
PMID- 25114863
TI - Triiodothyronine and breast cancer.
AB - The thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), are
essential for survival; they are involved in the processes of development,
growth, and metabolism. In addition to hyperthyroidism or hypothyroidism, THs are
involved in other diseases. The role of THs in the development and
differentiation of mammary epithelium is well established; however, their
specific role in the pathogenesis of breast cancer (BC) is controversial. Steroid
hormones affect many human cancers and the abnormal responsiveness of the mammary
epithelial cells to estradiol (E2) in particular is known to be an important
cause for the development and progression of BC. The proliferative effect of T3
has been demonstrated in various types of cancer. In BC cell lines, T3 may foster
the conditions for tumor proliferation and increase the effect of cell
proliferation by E2; thus, T3 may play a role in the development and progression
of BC. Studies show that T3 has effects similar to E2 in BC cell lines. Despite
controversy regarding the relationship between thyroid disturbances and the
incidence of BC, studies show that thyroid status may influence the development
of tumor, proliferation and metastasis.
PMID- 25114864
TI - Preventing breast cancer in LMICs via screening and/or early detection: The real
and the surreal.
AB - To review the present status of breast cancer (BC) screening/early detection in
low- and middle-income countries (LMICs) and identify the way forward, an open
focused search for articles was undertaken in PubMed, Google Scholar and Google,
and using a snowball technique, further articles were obtained from the reference
list of initial search results. In addition, a query was put up on ResearchGate
to obtain more references and find out the general opinion of experts on the
topic. Experts were also personally contacted for their opinion. Breast cancer
(BC) is the most common cancer in women in the world. The rise in incidence is
highest in LMICs where the incidence has often been much lower than high-income
countries. In spite of more women dying of cancer than pregnancy or childbirth
related causes in LMICs, most of the focus and resources are devoted to maternal
health. Also, the majority of women in LMICs present at late stages to a hospital
to initiate treatment. A number of trials have been conducted in various LMICs
regarding the use of clinical breast examination and mammography in various
combinations to understand the best ways of implementing a population level
screening/early detection of BC; nevertheless, more research in this area is
badly needed for different LMIC specific contexts. Notably, very few LMICs have
national level programs for BC prevention via screening/early detection and even
stage reduction is not on the public health agenda. This is in addition to other
barriers such as lack of awareness among women regarding BC and the presence of
stigma, inappropriate attitudes and lack of following proper screening behavior,
such as conducting breast self-examinations. The above is mixed with the apathy
and lack of awareness of policy makers regarding the fact that BC prevention is
much more cost-effective and humane than BC treatment. Implementation of
population level programs for screening/early detection of BC, along with use of
ways to improve awareness of women regarding BC, can prove critical in stemming
the increasing burden of BC in LMICs. Use of newer modalities such as
ultrasonography which is more suited to LMIC populations and use of mHealth for
awareness creation and increasing screening compliance are much needed extra
additions to the overall agenda of LMICs in preventing BC.
PMID- 25114866
TI - Adjuvant chemotherapy in breast cancer: To use or not to use, the anthracyclines.
AB - Breast cancer continues to be one of the leading causes of cancer mortality in
the world. The treatment generally involves multiple modalities including
surgery, radiation and/or chemotherapy. Anthracyclines, one of the first
chemotherapeutic agents introduced in the 1960s, has been the backbone for the
last 30 years and has been used extensively so far. However, the cardiac toxicity
and the concern for secondary hematological malignancy has always been a
challenge. A better understanding of the tumor biology, role of Her2 expression
and the discovery of trastuzumab and other anti-Her 2 agents along with other
effective novel therapeutic options, have revolutionized the treatment for breast
cancer. The role of anthracyclines has come under close scrutiny, especially in
the adjuvant setting for patients with early stage breast cancer and those with
low or intermediate risk of disease recurrence. Recent studies have highlighted
such a shift in the use of anthracyclines in both the academic and community
clinical practice. However, in patients with a high risk of relapse,
anthracyclines still hold promise. Ongoing clinical trials are underway to
further define the role of anthracyclines in such a patient population. This
review highlights the development, clinical utility, limitations and potential
future use of anthracyclines in the adjuvant setting for patients with breast
cancer. We consulted PubMed, Scopus, MEDLINE, ASCO annual symposium abstracts,
and http://clinicaltrials.gov/ for the purpose of this review.
PMID- 25114867
TI - Inflammatory breast cancer clusters: A hypothesis.
AB - Cancer clusters have long been a focus of interest because of the possibility of
identifying etiologic agents. Only on rare occasions, however, have such cluster
investigations been successful. One major difficulty in cluster investigations,
particularly in the area of breast cancer, is the long latent period. There have
been a number of publications providing a discouraging picture regarding cancer
cluster investigations. The possibility of learning from a cluster investigation,
however, is greatly increased if the cancer involved is relatively rare and if it
has a short latent period. Inflammatory breast cancer (IBC) fits these criteria
and is worth pursuing because of the strong evidence that environmental factors
play a major role. In this report we describe our experience with several
clusters and the lessons learned which are now being utilized to improve
investigation of future IBC clusters. The first IBC cluster that we evaluated was
in 2000, when we were asked to investigate an apparent cluster of IBC in Castro
Valley, California where three women in an office setting of 24 people were
diagnosed with IBC in a ten month period from May 1999 to March 2000. Our
investigation of this striking cluster did not yield a specific trigger for this
cluster but it did indicate that the women involved all had at least two IBC risk
factors that may well have made them susceptible to getting IBC. We are now
investigating another apparent cluster in Texas and are aware of several others
requiring careful consideration. We see a need for a consistent protocol for the
evaluation of IBC clusters focusing on the laboratory investigation of
environmental triggers, primarily infectious agents and chemical carcinogens.
PMID- 25114868
TI - Pleomorphic lobular carcinoma in situ of the breast: Can the evidence guide
practice?
AB - The clinical significance of pleomorphic lobular carcinoma in situ (PLCIS) is a
subject of controversy. As a consequence, there is a risk of providing
inconsistent management to patients presenting with PLCIS. This review aims to
establish whether the current guidelines for the management of PLCIS are
consistent with current evidence. A systematic electronic search was performed to
identify all English language articles regarding PLCIS management. The data was
analysed, specifically looking at: incidence of concurrent disease, recurrence
rates, long-term prognosis and PLCIS management. A search was also performed for
PLCIS management guidelines for the United Kingdom, United States, Canada,
Australia, Germany and pan-European. The results of the evidence analyses were
compared to the guidelines in order to establish whether the recommended
management is consistent with the published evidence. Nine studies (level 3-4
evidence), involving a total of 176 patients and five management guidelines (from
United Kingdom, United States, Australia and pan-European) were included in the
review. From the evidence, 46 of 93 (49%) patients were found to have PLCIS with
concurrent invasive disease on excision specimen analysis. Regarding recurrence
rates, 11 of 117 (9.4%) patients developed a recurrence of PLCIS. There were no
instances of invasive disease or ductal carcinoma in situ (DCIS) on recurrence
histology. There were no studies assessing long-term outcomes in PLCIS cases.
With regards to the management guidelines, the Association of Breast Surgery
(United Kingdom) and the National Breast and Ovarian Cancer Care (Australia) do
not mention PLCIS. The National Comprehensive Cancer Network (United States)
suggest considering excision of PLCIS with negative margins. The NHS Breast
Screening Programme (United Kingdom) and the European Society of Medical Oncology
(pan-European) recommend PLCIS should be treated as with DCIS. We conclude that
high quality evidence to inform guidance is lacking, thus recommendations are
relatively vague. However, based on the available evidence, it would seem prudent
to treat PLCIS in a similar manner to DCIS.
PMID- 25114865
TI - Green tea compounds in breast cancer prevention and treatment.
AB - Breast cancer is the most common cancer among women. In recent years, many in
vitro and in vivo studies indicate that green tea possesses anti-cancer effects.
The epidemiological studies, however, have produced inconclusive results in
humans. Likewise, results from animal models about the preventive or therapeutic
effects of green tea components are inconclusive. The mechanisms by which green
tea intake may influence the risk of breast cancer in humans remain elusive
mechanisms by which green tea intake may influence. Here, we review recent
studies of green tea polyphenols and their applications in the prevention and
treatment of breast cancer. Furthermore, we discuss the effect of green tea
components on breast cancer by reviewing epidemiological studies, animal model
studies and clinical trials. At last, we discuss the mechanisms by which green
tea components suppress the development and recurrence of breast cancer. A better
understanding of the mechanisms will improve the utilization of green tea in
breast cancer prevention and therapy and pave the way to novel prevention and
treatment strategies for breast cancer.
PMID- 25114870
TI - Subclinical hypothyroidism and pregnancy: the intersection of science, the art of
medicine, and public health policy.
PMID- 25114869
TI - Is exercise ignored in palliative cancer patients?
AB - Exercise and rehabilitation approaches in palliative care programs for cancer
patients affect patients' symptoms, physical functioning, muscle strength,
emotional wellbeing, psychological symptoms, functional capacities, quality of
life, mortality and morbidity positively. Based on scientific data, palliative
cancer patients should be recommended to participate in exercise programs. There
is no standard approach to recipe an exercise regimen for a palliative cancer
survivor. Studies for demonstrating the positive effects of exercising in
palliative care patients are increasing in number day by day. At this point,
increasing awareness about exercising in the entire team monitoring the patient
and our efforts in this matter seems to be very important.
PMID- 25114872
TI - Historical note: many steps led to the 'discovery' of thyroid-stimulating
hormone.
AB - Finding thyroid-stimulating hormone was a process rather than a circumscribed
event, and many talented persons participated over many years. Key early
participants were Bennet M. Allen and Philip E. Smith who had the misfortune just
prior to World War I of independently and simultaneously starting very similar
experiments with tadpoles. This led to a series of back and forth publications
attempting to establish priority for finding evidence of a thyrotropic factor in
the anterior pituitary. Decades of work by others would be required before
sophisticated biochemical techniques would bring us to our modern understanding.
PMID- 25114873
TI - The TRHR Gene Is Associated with Hypothalamo-Pituitary Sensitivity to
Levothyroxine.
AB - BACKGROUND: Thyroidectomized patients need variable doses of levothyroxine (LT4)
to obtain target thyroid-stimulating hormone (TSH) levels. Individual feedback
set-points have been hypothesized and the influence of several genes in the
regulation of the pituitary-thyroid axis has been demonstrated. OBJECTIVES: We
hypothesized that genetic variants of the TRHR gene could be associated with a
different hypothalamo-pituitary sensitivity to thyroid hormone feedback. METHODS:
We retrospectively analyzed 84 thyroidectomized patients with no residual thyroid
function and undetectable thyroglobulin levels. Patients were evaluated under LT4
resulting in TSH levels detectable but <0.5 MUIU/ml. The two SNPs rs3134105 and
rs3110040 were identified as informative markers of the TRHR gene. Genotyping was
performed using high-resolution melting technology. Genotype distribution was
compared between the patients and 99 euthyroid controls. RESULTS: The selected
SNPs were in linkage disequilibrium and only rs3134105 was further considered. A
significant difference between the three possible genotypes for rs3134105 was
found for TSH (p = 0.04) and free thyroxine (fT4)/TSH ratio (p = 0.02). Moreover,
despite similar serum concentrations of free triiodothyronine (fT3) and fT4,
carriers of at least one A allele of rs3134105 had significantly lower serum TSH
levels (p = 0.01) as well as higher fT3/TSH (p = 0.01) and fT4/TSH ratios (p <
0.01). CONCLUSIONS: We demonstrated an association between serum TSH levels and
discrete alleles of the TRHR gene in totally thyroidectomized patients under LT4
therapy. Therefore, the TRHR gene seems to be a determinant of hypothalamo
pituitary sensitivity to LT4.
PMID- 25114871
TI - 2014 European thyroid association guidelines for the management of subclinical
hypothyroidism in pregnancy and in children.
AB - This guideline has been produced as the official statement of the European
Thyroid Association guideline committee. Subclinical hypothyroidism (SCH) in
pregnancy is defined as a thyroid-stimulating hormone (TSH) level above the
pregnancy-related reference range with a normal serum thyroxine concentration.
Isolated hypothyroxinaemia (defined as a thyroxine level below the 2.5th centile
of the pregnancy-related reference range with a normal TSH level) is also
recognized in pregnancy. In the majority of SCH the cause is autoimmune
thyroiditis but may also be due to iodine deficiency. The cause of isolated
hypothyroxinaemia is usually not apparent, but iodine deficiency may be a factor.
SCH and isolated hypothyroxinaemia are both associated with adverse obstetric
outcomes. Levothyroxine therapy may ameliorate some of these with SCH but not in
isolated hypothyroxinaemia. SCH and isolated hypothyroxinaemia are both
associated with neuro-intellectual impairment of the child, but there is no
evidence that maternal levothyroxine therapy improves this outcome. Targeted
antenatal screening for thyroid function will miss a substantial percentage of
women with thyroid dysfunction. In children SCH (serum TSH concentration >5.5-10
mU/l) normalizes in >70% and persists in the majority of the remaining patients
over the subsequent 5 years, but rarely worsens. There is a lack of studies
examining the impact of SCH on the neuropsychological development of children
under the age of 3 years. In older children, the evidence for an association
between SCH and impaired neuropsychological development is inconsistent. Good
quality studies examining the effect of treatment of SCH in children are lacking.
PMID- 25114876
TI - Recombinant human thyrotropin use resulting in ovarian hyperstimulation: an
unusual side effect.
AB - A 43-year-old female was administered recombinant human thyrotropin-alpha
(Thyrogen(r); Genzyme Corp., Cambridge, Mass., USA) before a fluorodeoxyglucose
positron emission tomography/computed tomography (PET/CT) scan as part of an
evaluation of thyroid cancer recurrence. She was administered two doses of
Thyrogen only 4 weeks before for stimulated thyroglobulin measurement. The PET/CT
scan demonstrated enlarged ovaries which on subsequent conservative follow-up
resolved. This transient hyperstimulated state of the ovaries was presumed to be
related to Thyrogen injections received twice within a space of a month. Thyrogen
is being increasingly used for raising the level of thyroid-stimulating hormone
(TSH), besides thyroid hormone withdrawal for suspected recurrence of
differentiated thyroid carcinoma. Ovarian hyperstimulation has been reported as
an iatrogenic complication for in vitro fertilization with the presence of human
chorionic gonadotropin being invariably associated. Transient gestational
thyrotoxicosis has been reported to be related to promiscuous activation of the
thyrotropin receptor by chorionic gonadotropin. In our case it is possible that
due to the promiscuous stimulation, thyrotropin caused a follicle-stimulating
hormone (FSH)-like action resulting in ovarian hyperstimulation. The reason
behind this could be the shared sequence identity of the hormone-binding domains
of TSH and FSH receptors, or some mutation in the FSH receptor. In conclusion,
our case highlights a potential side effect of administering Thyrogen in females
of the reproductive age group.
PMID- 25114874
TI - A Progress Report of the IFCC Committee for Standardization of Thyroid Function
Tests.
AB - BACKGROUND: The IFCC Committee for Standardization of Thyroid Function Tests aims
at equivalence of laboratory test results for free thyroxine (FT4) and
thyrotropin (TSH). OBJECTIVES: This report describes the phase III method
comparison study with clinical samples representing a broad spectrum of thyroid
disease. The objective was to expand the feasibility work and explore the impact
of standardization/harmonization in the clinically relevant concentration range.
METHODS: Two sets of serum samples (74 for FT4, 94 for TSH) were obtained in a
clinical setting. Eight manufacturers participated in the study (with 13 FT4 and
14 TSH assays). Targets for FT4 were set by the international conventional
reference measurement procedure of the IFCC; those for TSH were based on the all
procedure trimmed mean. The manufacturers recalibrated their assays against these
targets. RESULTS: All FT4 assays were negatively biased in the mid- to high
concentration range, with a maximum interassay discrepancy of approximately 30%.
However, in the low range, the maximum deviation was approximately 90%. For TSH,
interassay comparability was reasonable in the mid-concentration range, but worse
in the pathophysiological ranges. Recalibration was able to eliminate the
interassay differences, so that the remaining dispersion of the data was nearly
entirely due to within-assay random error components. The impact of recalibration
on the numerical results was particularly high for FT4. CONCLUSIONS:
Standardization and harmonization of FT4 and TSH measurements is feasible from a
technical point of view. Because of the impact on the numerical values, the
implementation needs careful preparation with the stakeholders.
PMID- 25114877
TI - Simple core-needle biopsy for thyroid nodule, complicated tinnitus.
AB - BACKGROUND: Fine-needle aspiration is the procedure of choice for evaluating
thyroid nodules. Core-needle biopsy (CNB) is not included in the American Thyroid
Association recommendations for evaluating such nodules. CNB complications are
classically bleeding and hematomas. To our knowledge, no case of arteriovenous
fistula (AVF) secondary to a CNB has been reported, nor has any case of tinnitus
secondary to a post-CNB AVF. OBJECTIVES: To make the clinician aware of possible
vascular complications caused by CNB and the possibility of difficult pathology
reading caused by previous CNB. METHODS: A 44-year-old female is described who
was referred to our tertiary care center for left-sided pulsatile tinnitus. She
did report having had a CNB right before the tinnitus appeared. Conventional
angiography demonstrated a focal AVF originating from the left vertebral artery,
with reflux to the left vertebral venous plexus. A 6-mm stent was placed over the
site of the fistula via an endovascular approach, which solved both the
radiological and clinical documented problems. Moreover, CNB greatly complicated
pathology reading once total thyroidectomy was later performed. The suspected
area of invasion was an artifact due to the previous biopsies. CONCLUSION:
Although many authors recommend a CNB as an alternative modality in cases of
inconclusive cytology with fine-needle aspiration, it is not in the American
Thyroid Association recommendations. In cases of iatrogenic AVFs caused by a CNB,
angiography is recommended both as a diagnostic and therapeutic modality.
Stenting the fistula with an endoprosthesis can correct the problem immediately.
PMID- 25114875
TI - Development and application of a novel sensitive immunometric assay for
calcitonin in a large cohort of patients with medullary and differentiated
thyroid cancer, thyroid nodules, and autoimmune thyroid diseases.
AB - BACKGROUND: Serum calcitonin (sCT) is a useful biomarker for medullary thyroid
cancer (MTC). Consensus has not been reached concerning sCT measurements in the
evaluation of nodular thyroid disease (NTD). OBJECTIVE AND METHODS: We developed
a new immunofluorometric assay for sCT and have validated it in samples from 794
patients [203 with MTC, 205 with autoimmune thyroid disease (ATD), 248 with NTD,
80 with differentiated thyroid cancer (DTC) 'free of disease', 58 with chronic
renal failure (CRF)] and 178 normal individuals, including samples after
pentagastrin tests and samples from the washout of 92 FNA procedures in patients
with NTD or MTC. We also compared some samples from patients with low or high
calcitonin levels using both this assay and the Nichols Institute Diagnostics
(NID) assay. RESULTS: The assay's analytical sensitivity was 1.0 pg/ml.
Considering MTC patients prior to surgery, the cut-off values for the 95%
reference range were 11.1 pg/ml for males and 5.5 pg/ml for females and employing
the ROC curve were 18.4 pg/ml for males and 7.8 pg/ml for females. sCT in
patients with MTC was strongly correlated with disease status. Patients with NTD
and ATD did not present false-positive results. sCT measurements were
significantly correlated with age (excluding MTC and CRF). The NID test had a
strong correlation with our assay. A hook effect was observed only with
concentrations >200,000 pg/ml. CONCLUSIONS: We developed a novel sCT assay and
validated it in healthy subjects, as well as in a large cohort of patients with
MTC, NTD, ATD, DTC, and CRF.
PMID- 25114878
TI - Iodophilic synchronous phalangeal and choroidal metastasis from follicular
thyroid carcinoma: a case report and review.
AB - BACKGROUND: Follicular thyroid cancers constitute 15-20% of all thyroid tumors.
The usual mode of dissemination is via the hematogenous route. The most common
sites of distant metastasis are to the lungs and bones. OBJECTIVE: A case is
presented to demonstrate the unusual presentation of follicular cancer with
synchronous digital (distal phalanx of the little finger) and choroidal
metastasis that was responsive to radioiodine treatment. CASE REPORT: A 54-year
old female presented with swelling over the terminal part of the left little
finger with thyromegaly. Investigations revealed metastasis from follicular
thyroid cancer to the little finger along with pulmonary metastases. She
underwent total thyroidectomy with central compartment clearance followed by
(131)I therapy. Subsequent follow-up demonstrated complete regression of the
digital metastasis and partial regression of the choroidal metastasis which was
evaluated after the radioiodine scan that picked up the choroidal metastasis.
CONCLUSION: Follicular thyroid cancers can rarely spread to unusual sites like
the digits and choroid. This report highlights the synchronous presentation of
digital and choroidal metastasis which responded to (131)I therapy.
PMID- 25114879
TI - The Dilemma of Treating Subclinical Hypothyroidism: Risk that Current Guidelines
Do More Harm than Good.
PMID- 25114880
TI - Reply on the Letter by Stott et al. 'The Dilemma of Treating Subclinical
Hypothyroidism: Risk that Current Guidelines Do More Harm than Good'.
PMID- 25114881
TI - Letter regarding the Paper by Pearce et al. Entitled '2013 ETA Guideline:
Management of Subclinical Hypothyroidism'.
PMID- 25114882
TI - Diabetic foot risk factors in type 2 diabetes patients: a cross-sectional case
control study.
AB - BACKGROUND: Diabetic foot is a serious condition in patients with a long lasting
diabetes mellitus. Diabetic foot treated improperly may lead not only to delayed
ulceration healing, generalized inflammation, unnecessary surgical intervention,
but also to the lower limb amputation. The aim of this study was to compare
diabetic foot risk factors in population with type 2 diabetes and risk factors
for diabetes in healthy subjects. METHODS: The study included 900 subjects: 145
with diabetic foot, 293 with type 2 diabetes without diabetic foot and 462
healthy controls matched in terms of mean age, gender structure and
cardiovascular diseases absence. Study was conducted in Gastroenterology and
Metabolic Diseases Department, Medical University of Warsaw, Poland. In
statistical analysis a logistic regression model, U Mann-Whitney's and t-Student
test were used. RESULTS: The binomial logit models analysis showed that the risk
of diabetic foot in patients with type 2 diabetes was decreased by patient's age
(odds ratio [OR] = 0.94; 95% confidence interval [CI]: 0.92-0.96; p = 0.00001)
and hyperlipidaemia (OR = 0.54; 95% CI: 0.36-0.81; p = 0.01). In contrast, male
gender (OR = 2.83; 95% CI: 1.86-4.28; p = 0.00001) diabetes duration (OR = 1.04;
95% CI: 1.03-1.06; p = 0.0003), weight (OR = 1.04; 95% CI: 1.03-1.06; p =
0.00001), height (OR = 1.08; 95% CI: 1.05-1.11; p = 0.00001) and waist
circumference (OR = 1.028; 95% CI: 1.007-1.050; p = 0.006) increase the risk of
diabetic foot. The onset of type 2 diabetes in healthy subjects was increased by
weight (OR = 1.035; 95% CI: 1.024-1.046; p = 0.00001), WC (OR = 1.075; 95% CI:
1.055-1.096; p = 00001), hip circumference (OR = 1.03; 95% CI: 1.01-1.05; p =
0.005), overweight defined with body mass index (BMI) above 24,9 kg/m(2) (OR =
2.49; 95% CI: 1.77-3.51; p = 0.00001) and hyperlipidaemia (OR = 3.53; 95% CI:
2.57-4.84; p = 0.00001). CONCLUSIONS: Risk factors for Type 2 diabetes and
diabetic foot are only partially common. Study proved that patients who are prone
to developing diabetic foot experience different risk factors than patients who
are at risk of diabetes. Identification of relationship between diabetic foot and
diabetes risk factors in appropriate groups may help clinicians to focus on
certain factors in diabetic foot prevention.
PMID- 25114883
TI - Effects of glucose concentration in the medium on rat hepatocyte culture.
AB - PURPOSE: To determine the optimum culture conditions by investigating isolated
rat hepatocytes cultured in medium containing different glucose concentrations.
METHODS: Hepatocytes were isolated from rats using a two-step perfusion technique
and divided into the following two groups cultured in medium containing different
glucose concentrations: (1) low-glucose group and (2) high-glucose group. Total
cell count and viability of cultured rat hepatocytes and liver function
parameters (i.e., concentrations of albumin, ammonia, and urea in the culture
medium) were measured. The morphology of cultured rat hepatocytes was examined by
staining with hematoxylin and eosin, and albumin receptor expression was
confirmed by immunofluorescence. RESULTS: Total cell count and viability showed
smaller increases in the low-glucose group than the high-glucose group, although
the difference was not statistically significant (P = 0.112 and P = 0.147,
respectively). The levels of albumin (P = 0.943), ammonia (P = 0.744), and urea
(P = 0.709) were not significantly different between the two groups. In both
groups, the function of cultured hepatocytes decreased significantly over time.
The morphology of hepatocytes was well maintained in both groups at 3 days. On
day 7, the cytoplasm was transformed into a spindle shape. On day 10, these
changes were exaggerated, and were more prominent in the high-glucose group.
CONCLUSION: Morphological assessment indicated that low-glucose culture medium is
better than high-glucose culture medium for culturing of hepatocytes, although
there was not significantly different in functional assessment. The cultured
hepatocytes with low-glucose culture medium could be maintained for 7 days.
PMID- 25114884
TI - Long-term outcomes of intraoperative and perioperative albendazole treatment in
hepatic hydatidosis: single center experience.
AB - PURPOSE: The aim of this study was to evaluate long-term outcome of the
intraoperative and perioperative albendazole (ALB) treatment on the recurrence
and/or secondary hydatidosis. METHODS: One hundred and one patients with hepatic
hydatidosis were treated intraoperatively and perioperatively with ALB, in
addition to surgery. Perioperative ALB treatment was given in a dose of 12-15
mg/kg/day. The ALB treatment was started 13.27 +/- 14.34 days before the surgery,
and it was continued for 4.39 +/- 3.11 months postoperatively. A total of 1.7
ug/mL of ALB solution was used as a protoscolidal agent. The follow-up period was
134.55 +/- 51.56 months. RESULTS: Four patients died, with only one death was
secondary to hydatid disease (cerebral eccinococcus). There was only one
recurrence (1%) of hepatic hydatidosis. Early and late morbidity rates were 8.91%
and 7.92%, respectively. CONCLUSION: Our results suggest that intraoperative and
perioperative ALB is effective for the prevention of hepatic hydatidosis
recurrence and/or secondary hydatidosis.
PMID- 25114885
TI - Rationale and surgical technique of laparoscopic left lateral sectionectomy using
endoscopic staples.
AB - PURPOSE: Laparoscopic left lateral sectionectomy (LLLS) has been widely accepted
due to benefits of minimally invasive surgery. Some surgeons prefer to isolate
glissonian pedicles to segments II and III and to control individual pedicles
with surgical clips, whereas opt like to control glissonian pedicles
simultaneously using endoscopic stapling devices. The aim of this study was to
find the rationale of LLLS using endoscopic staples. METHODS: We retrospectively
analyzed and compared the clinical outcomes (operation time, drainage length,
transfusion, hospital stay, and complication rate) of 35 patients that underwent
LLLS between April 2004 and February 2012. Patients were dichotomized by surgical
technique based on whether glissonian pedicles were isolated and controlled (the
individual group, n = 21) or controlled using endoscopic staples at once (the
batch group, n = 14). RESULTS: Mean operation time was 265.3 +/- 21.3 minutes
(mean +/- standard deviation) in the individual group and 170 +/- 22.9 minutes in
the batch group. Operation time in the batch group was significantly shorter than
the individual group (P = 0.007). Mean drainage length was 4.8 +/- 1.6 and 2.6 +/
1.5 days in the individual and the batch group. There was significantly shorter
in the batch group, also (P = 0.006). No transfusion was required in the batch
group, but 4 patients in the individual group needed transfusion. Mean hospital
stay was 10.7 +/- 1.1 and 9.4 +/- 0.8 days in the individual and the batch groups
(P = 0.460). There were no significant complications or mortality in both groups.
CONCLUSION: LLLS using endoscopic staples (batch group) was found to be an easier
and safer technique without morbidity or mortality.
PMID- 25114886
TI - A comparison between surgical resection and radiofrequency ablation in the
treatment of hepatocellular carcinoma.
AB - PURPOSE: The aim of this study was to compare the therapeutic effects of
radiofrequency ablation (RFA) and hepatic resection (HR) with regards to
procedural morbidity, mortality, overall survival (OS) and disease-free survival
(DFS) rates in hepatocellular carcinoma (HCC) patients. METHODS: Retrospective
studies were performed based on the medical records of 129 patients who underwent
curative HR, and 57 who patients received RFA for HCC, between 2005 and 2009. The
inclusion criteria of HCC were the presence of three or fewer nodules 3 cm or
less in diameter or a single nodule of 5 cm or less. RESULTS: The 1-, 3- and 5
year OS rates in the HR group were 91.3%, 78.8%, and 64.9%, compared to 94.4%,
74.0%, and 74.0% in the RFA group, with no significant difference between the two
groups (P = 0.725). The estimated 1- and 3-year DFS rates were 70.0% and 53.0% in
the HR group and 65.2% and 24.7% in the RFA group, respectively. The DFS rates of
HR group were significantly higher than RFA group (P = 0.015). Multivariate
analysis identified that recurrence (P = 0.036) and portal hypertension (P =
0.036) were associated with OS and that portal hypertension (P = 0.048) and
increased serum alpha-FP (P = 0.008) were the factors significantly associated
with DFS. CONCLUSION: HCC within Milan criteria should consider hepatectomy as
the primary treatment if the patient's liver function and general conditions are
good enough to undergo surgical operation. But in that RFA revealed similar
overall survival to HR, RFA can be an alternative therapy for patients who are
eligible for surgical resection.
PMID- 25114887
TI - Four-channel single incision laparoscopic cholecystectomy using a snake
retractor: comparison between 3- and 4-channel SILC 4-channel single incision
cholecystectomy.
AB - PURPOSE: Single incision laparoscopic cholecystectomy (SILC) is a widely used
method of performing cholecystectomy. A common technique used in SILC is a 3
channel method. However, exposure of Calot's triangle is limited in conventional
3-channel SILC. Therefore, we herein report the adequacy and feasibility of 4
channel SILC using a snake retractor. METHODS: Four hundred and fifteen SILC
cases were performed between April 2010 and February 2013. We performed 326 SILC
cases between April 2010 and September 2012 using the 3-channel method. We
introduced a snake retractor for liver traction in October 2012, and 89 cases of
4-channel SILC using snake retractor have been performed since. RESULTS: Thirty
patients (9.2%) in the 3-channel SILC group, and 23 patients (25.8%) in the 4
channel SILC group, were treated with percutaneous transhepatic gallbladder
drainage insertion because of acute inflammation of the gallbladder (GB) before
operation (P < 0.001). The mean operating time was 53.0 +/- 25.8 minutes in the 3
channel SILC group and 51.9 +/- 18.6 minutes in the 4-channel SILC group (P =
0.709). In the 3-channel SILC group, mean hospital stay was 3.0 +/- 3.3 days
whereas it was 2.6 +/- 0.9 days in the 4-channel SILC group (P = 0.043). There
were a total 9 cases (2.1%) of additional port usages, 6 cases (1.8%) in the 3
channel SILC group and 3 cases (3.4%) in the 4-channel SILC group (P = 0.411),
due to cystic artery bleeding and bile leakage from gallbladder bed, but there
were no open conversions. CONCLUSION: Benign diseases of the GB can be operated
on using SILC with the 4-channel method using a snake retractor.
PMID- 25114888
TI - Role of resection for Bismuth type IV hilar cholangiocarcinoma and analysis of
determining factors for curative resection.
AB - PURPOSE: Extended liver resection may provide long-term survival in selected
patients with Bismuth type IV hilar cholangiocarcinoma (HCCA). The purpose of
this study was to identify anatomical factors that predict curative-intended
resection. METHODS: Thirty-three of 159 patients with Bismuth type IV HCCA
underwent major hepato-biliary resection with curative intent (CIR) between 2000
and 2010. Disease extent and anatomical variations were analyzed as factors
enabling CIR. RESULTS: CIR ratio with hilar trifurcation bile duct variation
(13/16) was significantly higher than that with other bile duct variation types
(18/25). Hilum to left second bile duct confluence and tumor infiltration over
left second bile duct confluence lengths in right-sided CIR were significantly
shorter than those lengths in left-sided CIR (10.8 +/- 4.9 and 2.7 +/- 0.8 mm vs.
16.5 +/- 8.4 and 7.0 +/- 5.3 mm, respectively). Left-sided CIR patients had a
marginally higher proportion of tumors invading <=5 mm over the right second
confluence than that in right-sided CIR patients (13/17 vs. 6/16; P = 0.061). The
3-year survival rate after CIR (28%) was significantly higher than after non-CIR
(6.1%). CONCLUSION: We recommend the criteria of CIR as bile duct variation type,
length of hilum to contralateral second bile duct confluence, and extent of tumor
infiltration over the second confluence for Bismuth type IV HCCA.
PMID- 25114889
TI - Pancreaticoduodenectomy for secondary periampullary cancer following extrahepatic
bile duct cancer resection.
AB - PURPOSE: This study addressed the feasibility and effect of surgical treatment of
metachronous periampullary carcinoma after resection of the primary extrahepatic
bile duct cancer. The performance of this secondary curative surgery is not well
documented. METHODS: We reviewed, retrospectively, the medical records of 10
patients who underwent pancreaticoduodenectomy (PD) for secondary periampullary
cancer following extrahepatic bileduct cancer resection from 1995 to 2011.
RESULTS: The mean age of the 10 patients at the second operation was 61 years
(range, 45-70 years). The primary cancers were 7 hilar cholangiocarcinomas, 2
middle common bile duct cancers, and one cystic duct cancer. The secondary
cancers were 8 distal common bile duct cancers and 2 carcinomas of the ampulla of
Vater. The second operations were 6 Whipple procedures and 4 pylorus-preserving
pancreaticoduodenectomies. The mean interval between primary treatment and
metachronous periampullary cancer was 20.6 months (range, 3.4-36.6 months). The
distal resection margin after primary resection was positive for high grade
dysplasia in one patient. Metachronous tumor was confirmed by periampullary
pathology in all cases. Four of the 10 patients had delayed gastric emptying (n =
2) or pancreatic fistula (n = 2) after reoperation. There were no perioperative
deaths. Median survival after PD was 44.6 months (range, 8.5-120.5 months).
CONCLUSION: Based on the postoperative survival rate, PD may provide an
acceptable protocol for resection in patients with metachronous periampullary
cancer after resection of the extrahepatic bile duct cancer.
PMID- 25114890
TI - Extremely rare case of extrahepatic duct phytobezoar treated with intraoperative
transenteral endoscopy.
AB - Phytobezoar is a rare cause of gastro-intestinal tract obstruction. Common sites
of phytobezoar are the stomach and small bowel. Naturally, extrahepatic duct
phytobezoar is near impossible due to anatomical structure and location such as
ampulla of vater, common bile duct and bifurcation of bile duct. Here, we present
an extremely rare case of extrahepatic duct phytobezoar that resulted in
abdominal pain. We successfully treated the case with extraoperative transenteral
endoscopic removal of phytobezoar. For its great rarity and particular treatment
approach, we report this case with review of literature.
PMID- 25114891
TI - Acute cholecystitis associated with Clonorchis sinensis infection.
AB - Clonorchis sinensis is one of the most common causes of trematodiasis that is
caused by the ingestion of raw fish contaminated with infective cysts. The adult
flukes are predominantly present in the intrahepatic bile ducts, but occasionally
they may be found in the pancreatic duct and extrahepatic bile ducts. The
clinical manifestations depend on the number of flukes, the period of
infestation, and complications such as pericholangitic abscess, cholangitis, bile
duct stones, and cholangiocarcinoma. However, primary acute cholecystitis
associated with C. sinensis infection is extremely rare. Herein, we report on a
case of primary acute cholecystitis associated with C. sinensis infection.
PMID- 25114892
TI - Salvage dual graft living donor liver transplantation after major hepatectomy.
AB - Salvage living donor liver transplantation (LDLT) after major hepatectomy has
been considered a challenging procedure due to operative complexity. We report a
successful case of salvage dual graft LDLT after right hepatectomy. A 48-year-old
male was transferred to Daegu Catholic University Medical Center because of
duodenal variceal bleeding. He underwent right hepatectomy due to hepatocellular
carcinoma four years prior. We performed LDLT with dual graft from his wife and
sister. During operation, portal vein anastomosis of the right lobe graft was
performed using an interposing cadaveric iliac vein graft and the right
gastroepiploic artery was anastomosed to the hepatic artery of the left lobe
graft. Adequate graft inflow was demonstrated by postoperative imaging studies.
He has been doing well with normal graft function for 31 months. Salvage dual
graft LDLT could be undertaken successfully in patients with prior major
hepatectomy under accurate preoperative planning and proper surgical techniques.
PMID- 25114894
TI - Trends in the incidence of human papillomavirus-related noncervical and cervical
cancers in Alberta, Canada: a population-based study.
AB - INTRODUCTION: Recent epidemiologic studies have suggested that the incidence of
noncervical cancers associated with human papillomavirus (HPV) is increasing. We
assessed temporal, age-specific and sex-specific changes in the incidence of HPV
associated cancers in a population-based study. METHODS: We used the Alberta
Cancer Registry, a registry of all cancers diagnosed in the province of Alberta,
Canada, to identify patients with cancers of the oropharynx, cervix, vulva,
vagina, anus and penis (cancers associated with HPV) between Jan. 1, 1975, and
Dec. 31, 2009. We estimated the age-standardized incidence of each cancer by sex-
and age-specific group and assessed the annual percentage change using joinpoint
regression. RESULTS: The age-standardized incidence of oropharyngeal cancers
increased for each 5-year interval of the study period among men (annual
percentage change 3.4, p < 0.001) and women (annual percentage change 1.5, p =
0.009). For anal cancers, the age-standardized rates increased among women
(annual percentage change 2.2, p < 0.001) and men (annual percentage change 1.8,
p = 0.008). The age-standardized incidence of cervical cancer increased with age,
reaching an annual percentage change of -3.5 among women aged 75-84 years (p =
0.04). The rates of other HPV-associated cancers (vulvar, vaginal and penile)
showed little change. INTERPRETATION: Our findings showed increases in the
incidence of the HPV-associated cancers of the oropharynx and anus among men and
women, and increases in cervical cancer among younger women. The incidence of HPV
related cancers in younger age groups should continue to be monitored. Programs
to prevent HPV infection, such as vaccination, should be considered for males as
well as females.
PMID- 25114895
TI - Expression of pain among Mi'kmaq children in one Atlantic Canadian community: a
qualitative study.
AB - BACKGROUND: First Nation children have the highest rates of pain-related
conditions among Canadian children, yet there is little research on how this
population expresses its pain or how and whether the pain is successfully
treated. The aim of this study was to understand how Mi'kmaq children express
pain and how others interpret it. METHODS: We conducted a qualitative
ethnographic study in a large Canadian Mi'kmaq community using interviews and
conversation sessions. Participants included children and youth (n = 76), parents
(n = 12) teachers (n = 7), elders (n = 6) and health care professionals (n = 13).
RESULTS: Interpretive descriptive analysis was used and themes regarding pain
expression, care seeking and pain management were identified. Pain expression
included stoicism and hiding behaviour, and, when pain was discussed, it was via
storytelling and descriptive language, such as similes. Participants reported
feeling unheard, stereotyped and frustrated when they sought pain care.
Frustration led to avoidance of seeking further care, perceptions of racism and
repeat visits because of unsuccessful previous treatment. Participants voiced
concerns about the utility of the numeric and faces pain scales to describe pain
meaningfully. Positive encounters occurred when participants felt respected and
heard. INTERPRETATION: Mi'kmaq children are stoic and often hide their pain.
Community members feel frustrated and discriminated against when their pain is
not identified, and conventional pain assessment tools may not be useful. If
clinicians consider cultural context, build trust and allow for additional time
to assess pain via storytelling or word descriptions as well as a family-centred
approach, better pain care may occur.
PMID- 25114897
TI - The construct validity and reliability of an assessment tool for competency in
cochlear implant surgery.
AB - INTRODUCTION: We introduce a rating tool that objectively evaluates the skills of
surgical trainees performing cochlear implant surgery. METHODS: Seven residents
and seven experts performed cochlear implant surgery sessions from mastoidectomy
to cochleostomy on a standardized virtual reality temporal bone. A total of
twenty-eight assessment videos were recorded and two consultant otolaryngologists
evaluated the performance of each participant using these videos. RESULTS:
Interrater reliability was calculated using the intraclass correlation
coefficient for both the global and checklist components of the assessment
instrument. The overall agreement was high. The construct validity of this
instrument was strongly supported by the significantly higher scores in the
expert group for both components. CONCLUSION: Our results indicate that the
proposed assessment tool for cochlear implant surgery is reliable, accurate, and
easy to use. This instrument can thus be used to provide objective feedback on
overall and task-specific competency in cochlear implantation.
PMID- 25114896
TI - Unique pattern of component gene disruption in the NRF2 inhibitor KEAP1/CUL3/RBX1
E3-ubiquitin ligase complex in serous ovarian cancer.
AB - The NFE2-related factor 2 (NRF2) pathway is critical to initiate responses to
oxidative stress; however, constitutive activation occurs in different cancer
types, including serous ovarian carcinomas (OVCA). The KEAP1/CUL3/RBX1 E3
ubiquitin ligase complex is a regulator of NRF2 levels. Hence, we investigated
the DNA-level mechanisms affecting these genes in OVCA. DNA copy-number loss
(CNL), promoter hypermethylation, mRNA expression, and sequence mutation for
KEAP1, CUL3, and RBX1 were assessed in a cohort of 568 OVCA from The Cancer
Genome Atlas. Almost 90% of cases exhibited loss-of-function alterations in any
components of the NRF2 inhibitory complex. CNL is the most prominent mechanism of
component disruption, with RBX1 being the most frequently disrupted component.
These alterations were associated with reduced mRNA expression of complex
components, and NRF2 target gene expression was positively enriched in 90% of
samples harboring altered complex components. Disruption occurs through a unique
DNA-level alteration pattern in OVCA. We conclude that a remarkably high
frequency of DNA and mRNA alterations affects components of the KEAP1/CUL3/RBX1
complex, through a unique pattern of genetic mechanisms. Together, these results
suggest a key role for the KEAP1/CUL3/RBX1 complex and NRF2 pathway deregulation
in OVCA.
PMID- 25114898
TI - Improvement of oxidative and metabolic parameters by cellfood administration in
patients affected by neurodegenerative diseases on chelation treatment.
AB - OBJECTIVE: This prospective pilot study aimed at evaluating the effects of
therapy with antioxidant compounds (Cellfood, and other antioxidants) on patients
affected by neurodegenerative diseases (ND), who displayed toxic metal burden and
were subjected to chelation treatment with the chelating agent calcium disodium
ethylenediaminetetraacetic acid (CaNa2EDTA or EDTA). METHODS: Two groups of
subjects were studied: (a) 39 patients affected by ND and (b) 11 subjects
unaffected by ND (controls). The following blood parameters were analyzed before
and after three months' treatment with chelation+Cellfood or chelation+other
antioxidants: oxidative status (reactive oxygen species, ROS; total antioxidant
capacity, TAC; oxidized LDL, oxLDL; glutathione), homocysteine, vitamin B12, and
folate. RESULTS: After 3-months' chelation+Cellfood administration oxLDL
decreased, ROS levels were significantly lower, and TAC and glutathione levels
were significantly higher than after chelation+other antioxidants treatment, both
in ND patients and in controls. Moreover, homocysteine metabolism had also
improved in both groups. CONCLUSIONS: Chelation+Cellfood treatment was more
efficient than chelation+other antioxidants improving oxidative status and
homocysteine metabolism significantly in ND patients and controls. Although
limited to a small number of cases, this study showed how helpful antioxidant
treatment with Cellfood was in improving the subjects' metabolic conditions.
PMID- 25114899
TI - Sensitization of cancer cells through reduction of total Akt and downregulation
of salinomycin-induced pAkt, pGSk3beta, pTSC2, and p4EBP1 by cotreatment with MK
2206.
AB - MK-2206 is an inhibitor of Akt activation. It has been investigated as an
anticancer drug in clinical trials assessing the potential of pAkt targeting
therapy. The purpose of this study was to identify conditions that increase the
sensitivity of cancer cells to MK-2206. We found that the treatment of cancer
cells with a high concentration of salinomycin (Sal) reduced total Akt protein
levels but increased activated Akt levels. When cancer cells were cotreated with
MK-2206 and Sal, both pAkt and total Akt levels were reduced. Using microscopic
observation, an assessment of cleaved PARP, FACS analysis of pre-G1 region, and
Hoechst staining, we found that Sal increased apoptosis of MK-2206-treated cancer
cells. These results suggest that cotreatment with MK-2206 and Sal sensitizes
cancer cells via reduction of both pAkt and total Akt. Furthermore, cotreatment
of cancer cells with Sal and MK-2206 reduced pp70S6K, pmTOR, and pPDK1 levels. In
addition, Sal-induced activation of GSK3beta, TSC2, and 4EBP1 was abolished by MK
2206 cotreatment. These results suggest that cotreatment using MK-2206 and Sal
could be used as a therapeutic method to sensitize cancer cells through targeting
of the PI3K/Akt/mTOR pathway. Our findings may contribute to the development of
MK-2206-based sensitization therapies for cancer patients.
PMID- 25114901
TI - Aromatherapy: does it help to relieve pain, depression, anxiety, and stress in
community-dwelling older persons?
AB - To examine the effectiveness of an aromatherapy programme for older persons with
chronic pain. The community-dwelling elderly people who participated in this
study underwent a four-week aromatherapy programme or were assigned to the
control group, which did not receive any interventions. Their levels of pain,
depression, anxiety, and stress were collected at the baseline and at the
postintervention assessment after the conclusion of the four-week programme.
Eighty-two participants took part in the study. Forty-four participants (37
females, 7 males) were in the intervention group and 38 participants (30 females,
8 males) were in the control group. The pain scores were 4.75 (SD 2.32) on a 10
point scale for the intervention group and 5.24 (SD 2.14) for the control group
before the programme. There was a slight reduction in the pain score of the
intervention group. No significant differences were found in the same-group and
between-group comparisons for the baseline and postintervention assessments. The
depression, anxiety, and stress scores for the intervention group before the
programme were 11.18 (SD 6.18), 9.64 (SD 7.05), and 12.91 (SD 7.70),
respectively. A significant reduction in negative emotions was found in the
intervention group (P<0.05). The aromatherapy programme can be an effective tool
to reduce pain, depression, anxiety, and stress levels among community-dwelling
older adults.
PMID- 25114900
TI - Novel resveratrol and 5-fluorouracil coencapsulated in PEGylated nanoliposomes
improve chemotherapeutic efficacy of combination against head and neck squamous
cell carcinoma.
AB - Increasing consumption of tobacco and alcohol has led to a steady increase in the
incidence of head and neck cancers in Asia. The drawbacks associated with the
existing chemotherapeutic and surgical interventions have necessitated the
development of a safer alternative for therapy of head and neck cancers. In this
study we have explored the synergistic therapeutic potential of a phytochemical
and chemotherapeutic agent using PEGylated liposomes as a delivery vehicle.
Resveratrol and 5-fluorouracil were successfully coencapsulated in a single
PEGylated nanoliposome. The thermal analysis and the nuclear magnetic resonance
results revealed that resveratrol localized near the glycerol backbone of the
liposomal membrane while 5-fluorouracil localized closer to the phosphate moiety,
which influenced the release kinetics of both drugs. The nanoformulation was
tested in vitro on a head and neck cancer cell line NT8e and was found to exhibit
a GI50 similar to that of free 5-fluorouracil. Further, gene expression studies
showed that the combination of resveratrol and 5-fluorouracil exhibited different
effects on different genes that may influence the net antagonistic effect. The
coencapsulation of resveratrol and 5-fluorouracil in a liposomal nanocarrier
improved the cytotoxicity in comparison with the free drug combination when
tested in vitro.
PMID- 25114903
TI - miRSeq: a user-friendly standalone toolkit for sequencing quality evaluation and
miRNA profiling.
AB - MicroRNAs (miRNAs) present diverse regulatory functions in a wide range of
biological activities. Studies on miRNA functions generally depend on determining
miRNA expression profiles between libraries by using a next-generation sequencing
(NGS) platform. Currently, several online web services are developed to provide
small RNA NGS data analysis. However, the submission of large amounts of NGS
data, conversion of data format, and limited availability of species bring
problems. In this study, we developed miRSeq to provide alternatives. To test the
performance, we had small RNA NGS data from four species, including human, rat,
fly, and nematode, analyzed with miRSeq. The alignments results indicate that
miRSeq can precisely evaluate the sequencing quality of samples regarding
percentage of self-ligation read, read length distribution, and read category.
miRSeq is a user-friendly standalone toolkit featuring a graphical user interface
(GUI). After a simple installation, users can easily operate miRSeq on a PC or
laptop by using a mouse. Within minutes, miRSeq yields useful miRNA data,
including miRNA expression profiles, 3' end modification patterns, and isomiR
forms. Moreover, miRSeq supports the analysis of up to 105 animal species,
providing higher flexibility.
PMID- 25114902
TI - Comparison of the Freiburg and Charlson comorbidity indices in predicting overall
survival in elderly patients with newly diagnosed multiple myeloma.
AB - Multiple myeloma occurs primarily in elderly patients. Considering the high
prevalence of comorbidities, comorbidity is an important issue for the management
of myeloma. However, the impact of comorbidity on clinical outcomes has not been
fully investigated. We retrospectively analyzed patients with newly diagnosed
myeloma. Comorbidities were assessed based on the Charlson comorbidity index
(CCI) and the Freiburg comorbidity index (FCI). The CCI is a summary measure of
19 comorbid conditions. FCI is determined by performance status, renal
impairment, and lung disease. This study included 127 patients with a median age
of 71 years. Approximately half of the patients had additional disorders at the
time of diagnosis, and diabetes mellitus was the most frequent diagnosis (18.9%).
The most significant factors for prognosis among patient-related conditions were
a history of solid cancer and performance status (ECOG>=2). The FCI score was
divided into 3 groups (0, 1, and 2-3), and the CCI score was divided into 2
groups (2-3 and >=4). FCI was a strong prognostic tool for OS (P>0.001) and
predicted clinical outcome better than CCI (P=0.059). In conclusion, FCI was more
useful than CCI in predicting overall survival in elderly patients with myeloma.
PMID- 25114904
TI - A simple model to assess the probability of invasion in ductal carcinoma in situ
of the breast diagnosed by needle biopsy.
AB - OBJECTIVES: The aim of the study was to develop a clinical prediction model for
assessing the probability of having invasive cancer in the definitive surgical
resection specimen in patients with biopsy diagnosis of ductal carcinoma in situ
(DCIS) of the breast, to facilitate decision making regarding axillary surgery.
METHODS: In 349 women with DCIS, predictors of invasion in the definitive
resection specimen were identified. A model to predict the probability of
invasion was developed and subsequently simplified to divide patients into two
risk categories. The model's performance was validated on another patient
population. RESULTS: Multivariate logistic regression revealed four independent
predictors of invasion: (i) suspicious (micro)invasion in the biopsy specimen;
(ii) visibility of the lesion on ultrasonography; (iii) size of the lesion on
mammography>30 mm; (iv) clinical palpability of the lesion. The actual frequency
of invasion in the high-risk patient group in the test and validation population
was 52.6% and 48.3%, respectively; in the low-risk group it was 16.8% and 7.1%,
respectively. CONCLUSION: The model proved to have good performance. In patients
with a low probability of invasion, an axillary procedure can be omitted without
a substantial risk of additional surgery.
PMID- 25114905
TI - Therapeutic potential of tacrolimus on acute myocardial infarction in minipigs:
analysis with serial cardiac magnetic resonance and changes at histological and
protein levels.
AB - This study investigates the therapeutic potential of intracoronary tacrolimus
against acute myocardial infarction (AMI) in minipigs with serial cardiac
magnetic resonance (CMR) and changes at histological and protein levels. Twelve
minipigs subjected to permanent left anterior descending artery ligation were
randomized as tac-treated group (n=6, with intracoronary tacrolimus treatment)
and controls (n=6). CMR with cine and late gadolinium enhancement (LGE) studies
were performed on postoperative days 2, 5, and 21. There were no significant
differences in left ventricular function (LVF), contractility, and LGE between
the two groups on day 2. On day 5, the tac-treated group showed a significantly
higher ejection fraction, smaller infarct, and lower day-5/day-2 infarct ratio
than controls. On day 21, the controls demonstrated further deterioration of LVF
and infarct. Contrastingly, the tac-treated animals demonstrated preservation of
LVF, contractility, significantly smaller infarct, and lower day-21/day-2 infarct
ratios compared with those on day 5 and controls. The in vivo CMR results were
correlated with in vitro findings on histology, immunostaining, and Western
blotting which revealed significantly less fibrosis, higher vascularities, less
CD68+ and CD40+ inflammatory cells, lower expressions of inflammatory (MMP-9, NF
kappaB, and TNF-alpha), and apoptotic (Bax, Caspase-3, c-PARP) biomarkers,
respectively, in tac-treated AMI minipigs than controls.
PMID- 25114906
TI - Therapeutic efficacy of vitamin E delta-tocotrienol in collagen-induced rat model
of arthritis.
AB - Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease primarily
involving inflammation of the joints. Although the management of the disease has
advanced significantly in the past three decades, there is still no cure for RA.
The aim of this study was to determine the therapeutic efficacy of delta
tocotrienol, in the rat model of collagen-induced arthritis (CIA). Arthritis was
induced by intradermal injection of collagen type II emulsified in complete
Freund's adjuvant. CIA rats were orally treated with delta-tocotrienol (10 mg/kg)
or glucosamine hydrochloride (300 mg/kg) from day 25 to 50. Efficacy was assessed
based on the ability to reduce paw edema, histopathological changes, suppression
of collagen-specific T-cells, and a reduction in C-reactive protein (CRP) levels.
It was established that delta-tocotrienol had the most significant impact in
lowering paw edema when compared to glucosamine treatment. Paw edema changes
correlated well with histopathological analysis where there was a significant
reversal of changes in groups treated with delta-tocotrienol. The results suggest
that delta-tocotrienol is efficient in amelioration of collagen-induced
arthritis. Vitamin E delta-tocotrienol may be of therapeutic value against
rheumatoid arthritis.
PMID- 25114907
TI - The effectiveness of functional electrical stimulation based on a normal gait
pattern on subjects with early stroke: a randomized controlled trial.
AB - OBJECTIVE: To investigate the effectiveness of four-channel FES based on a normal
gait pattern on improving functional ability in subjects early after ischemic
stroke. METHODS: Forty-five subjects were randomly assigned into a four-channel
FES group (n=16), a placebo group (n=15), or a dual-channel group (n=14).
Stimulation lasted for 30 min in each session with 1 session/day, 5 days a week
for 3 weeks. All subjects were assessed at baseline, at 3 weeks of treatment, and
at 3 months after the treatment had finished. The assessments included Fugl-Meyer
Assessment (FMA), the Postural Assessment Scale for Stroke Patients (PASS), Berg
Balance Scale (BBS), Functional Ambulation Category (FAC), and the Modified
Barthel Index (MBI). RESULTS: All 3 groups demonstrated significant improvements
in all outcome measurements from pre- to posttreatment and further gains at
followup. The score of FMA and MBI improved significantly in the four-channel
group at the end of the 3 weeks of training. And the scores of PASS, BBS, MBI,
and FAC in the four-channel group were significantly higher than those of the
placebo group. CONCLUSIONS: This study indicated that four-channel FES can
improve motor function, balance, walking ability, and performance of activities
of daily living in subjects with early ischemic stroke.
PMID- 25114908
TI - The protective effect of Agaricus blazei Murrill, submerged culture using the
optimized medium composition, on alcohol-induced liver injury.
AB - Agaricus blazei Murrill (ABM), an edible mushroom native to Brazil, is widely
used for nonprescript and medicinal purposes. Alcohol liver disease (ALD) is
considered as a leading cause for a liver injury in modern dietary life, which
can be developed by a prolonged or large intake of alcohol. In this study, the
medium composition of ABM was optimized using response surface methodology for
maximum mycelial biomass and extracellular polysaccharide (EPS) production. The
model predicts to gain a maximal mycelial biomass and extracellular
polysaccharide at 1.047 g/100 mL, and 0.367 g/100 mL, respectively, when the
potato is 29.88 g/100 mL, the glucose is 1.01 g/100 mL, and the bran is 1.02
g/100 mL. The verified experiments showed that the model was significantly
consistent with the model prediction and that the trends of mycelial biomass and
extracellular polysaccharide were predicted by artificial neural network. After
that, the optimized medium was used for the submerged culture of ABM. Then,
alcohol-induced liver injury in mice model was used to examine the protective
effect of ABM cultured using the optimized medium on the liver. And the hepatic
histopathological observations showed that ABM had a relatively significant role
in mice model, which had alcoholic liver damage.
PMID- 25114910
TI - Phylogenetic and in silico functional analyses of thermostable-direct hemolysin
and tdh-related encoding genes in Vibrio parahaemolyticus and other Gram-negative
bacteria.
AB - Emergence and spread of pandemic strains of Vibrio parahaemolyticus have drawn
attention to make detailed study on their genomes. The pathogenicity of V.
parahaemolyticus has been associated with thermostable-direct hemolysin (TDH)
and/or TDH-related hemolysin (TRH). The present study evaluated characteristics
of tdh and trh genes, considering the phylogenetic and in silico functional
features of V. parahaemolyticus and other bacteria. Fifty-two tdh and trh genes
submitted to the GenBank were analyzed for sequence similarity. The promoter
sequences of these genes were also analyzed from transcription start point to -35
regions and correlated with amino acid substitution within the coding regions.
The phylogenetic analysis revealed that tdh and trh are highly distinct and also
differ within the V. parahaemolyticus strains that were isolated from different
geographical regions. Promoter sequence analysis revealed nucleotide
substitutions and deletions at -18 and -19 positions among the pandemic,
prepandemic, and nonpandemic tdh sequences. Many amino acid substitutions were
also found within the signal peptide and also in the matured protein region of
several TDH proteins as compared to TDH-S protein of pandemic V.
parahaemolyticus. Experimental evidences are needed to recognize the importance
of substitutions and deletions in the tdh and trh genes.
PMID- 25114909
TI - Heavy silicone oil and intraocular inflammation.
AB - In the past two decades, many advances have been made in vitrectomy
instrumentation, surgical techniques, and the use of different tamponade agents.
These agents serve close retinal breaks, confine eventual retinal redetachment,
and prevent proliferative vitreoretinopathy (PVR). Long-acting gases and silicone
oil are effective internal tamponade agents; however, because their specific
gravity is lower than that of the vitreous fluid, they may provide adequate
support for the superior retina but lack efficacy for the inferior retina,
especially when the fill is subtotal. Thus, a specific role may exist for an
internal tamponade agent with a higher specific gravity, such as heavy silicone
oils (HSOs), Densiron 68, Oxane HD, HWS 45-300, HWS 46-3000, and HeavySil. Some
clinical evidence seems to presume that heavy tamponades are more prone to
intraocular inflammation than standard silicone if they remain in the eye for
several months. In this review, we discuss the fundamental clinical and
biochemical/molecular mechanisms involved in the inflammatory response after the
use of heavy tamponade: toxicity due to impurities or instability of the agent,
direct toxicity and immunogenicity, oil emulsification, and mechanical injury due
to gravity. The physical and chemical properties of various HSOs and their
efficacy and safety profiles are also described.
PMID- 25114911
TI - Epigenetic silencing of CXCR4 promotes loss of cell adhesion in cervical cancer.
AB - In the network of chemokine signaling pathways, recent reports have described the
SDF-1alpha/CXCR4 axis and its role in cancer progression and metastasis.
Interestingly, we found downregulation of CXCR4 at both transcript and protein
level in cervical cancer cell lines and primary tumors. We also found CXCR4
promoter hypermethylation in cervical cancer cell lines and primary biopsy
samples. DNA hypomethylating drug 5-AZA-2'-deoxycytidine and histone deacetylase
inhibitor Trichostatin A treatments in cell lines reactivate both CXCR4
transcription and protein expression. Cell adhesion assay demonstrated that
autocrine SDF-1alpha promotes the loss of cell adhesion while paracrine SDF
1alpha predominantly protects the normal cervical cells from loss of cell
adhesion. Cervical cancer cell line C-33A having increased expression of CXCR4
after TSA treatment showed increased cell adhesion by paracrine source of SDF
1alpha in comparison to untreated C-33A. These findings demonstrate the first
evidence that epigenetic silencing of CXCR4 makes the cells inefficient to
respond to the paracrine source of SDF-1alpha leading to loss of cell adhesion,
one of the key events in metastases and progression of the disease. Our results
provide novel insight of SDF-1alpha/CXCR4 signaling in tumor microenvironment
which may be promising to further delineate molecular mechanism of cervical
carcinogenesis.
PMID- 25114912
TI - Modulation of circulating macrophage migration inhibitory factor in the elderly.
AB - Aging increases the risk for cardiovascular morbidity and mortality. Chronic low
grade inflammation deteriorates vascular function, increases age-related vascular
stiffness, and affects hemodynamics. The proinflammatory cytokine macrophage
migration inhibitory factor (MIF) is a major mediator of atherosclerosis. Plasma
MIF levels are associated with arterial stiffness, a hallmark of vascular aging.
Preclinical studies show that blockade of MIF leads to atherosclerotic plaque
regression. Nutritional approaches provide opportunities to counteract age
related inflammation. Following a chronic dietary supplementation with the
micronutrient nitrate has been demonstrated to improve vascular stiffness.
Whether dietary nitrate affects circulating MIF levels is not known. In a
randomized placebo-controlled, double-blinded study, elderly subjects received a
dietary nitrate supplementation for 4 weeks. Dietary nitrate led to a decrease in
plasma MIF levels in the elderly and to an improvement in vascular functions.
This was associated with a reduction in central systolic blood pressure. Our data
show that supplementation with dietary nitrate is associated with a reduction of
circulating MIF levels along with an improvement in vascular function. This
supports the concept of dietary approaches to modulate age-related changes of
vascular functions.
PMID- 25114915
TI - Molecular image-guided theranostic and personalized medicine 2013.
PMID- 25114913
TI - Profiling of biomarkers for the exposure of polycyclic aromatic hydrocarbons:
lamin-A/C isoform 3, poly[ADP-ribose] polymerase 1, and mitochondria copy number
are identified as universal biomarkers.
AB - This study investigated the profiling of polycyclic aromatic hydrocarbon- (PAH-)
induced genotoxicity in cell lines and zebrafish. Each type of cells displayed
different proportionality of apoptosis. Mitochondrial DNA (mtDNA) copy number was
dramatically elevated after 5-day treatment of fluoranthene and pyrene. The
notable deregulated proteins for PAHs exposure were displayed as follows: lamin
A/C isoform 3 and annexin A1 for benzopyrene; lamin-A/C isoform 3 and DNA
topoisomerase 2-alpha for pentacene; poly[ADP-ribose] polymerase 1 (PARP-1) for
fluoranthene; and talin-1 and DNA topoisomerase 2-alpha for pyrene. Among them,
lamin-A/C isoform 3 and PARP-1 were further confirmed using mRNA and protein
expression study. Obvious morphological abnormalities including curved backbone
and cardiomegaly in zebrafish were observed in the 54 hpf with more than 400 nM
of benzopyrene. In conclusion, the change of mitochondrial genome (increased
mtDNA copy number) was closely associated with PAH exposure in cell lines and
mesenchymal stem cells. Lamin-A/C isoform 3, talin-1, and annexin A1 were
identified as universal biomarkers for PAHs exposure. Zebrafish, specifically at
embryo stage, showed suitable in vivo model for monitoring PAHs exposure to
hematopoietic tissue and other organs.
PMID- 25114916
TI - Physiological and behavioral stress and anxiety in children with autism spectrum
disorders during routine oral care.
AB - BACKGROUND: Children with autism spectrum disorders (ASD) commonly exhibit
uncooperative behaviors which impede oral care. Previous studies have utilized
dentist-report measures of uncooperative behaviors in children with ASD but none
have utilized an objective measure of children's behavior or a physiological
measure of distress. This study investigated behavioral and physiological
distress in children with ASD during routine oral care and examined factors
associated with this distress. METHODS: Participants were 44 children (n=22
typical, n=22 ASD) aged 6-12 receiving routine dental cleanings. Behavioral and
physiological measures of stress and anxiety were collected during dental
cleanings. RESULTS: Children with ASD exhibited greater distress, compared to the
typical group, on dentist-report and researcher-coded measures of overt distress
behaviors and on physiological measures. Correlations between physiological and
behavioral measures of distress were found in the ASD but not in the typical
group. Behavioral distress was correlated with age in the typical group and with
expressive communication ability and sensory processing difficulties in the ASD
group; physiological distress was correlated with parent-report of anxiety in the
typical group and sensory processing difficulties in the ASD group. CONCLUSIONS:
Novel strategies may be required to decrease behavioral and physiological
distress in children with ASD in the dental clinic.
PMID- 25114914
TI - Antidiabetic effect of Sida cordata in alloxan induced diabetic rats.
AB - Medicinal plants are efficient ameliorator of oxidative stress associated with
diabetes mellitus. In this study, ethyl acetate fraction (SCEE) of Sida cordata
was investigated for scientific validation of its folk use in diabetes.
Antidiabetic effect of SCEE was confirmed by antihyperglycemic activity in normal
glucose loaded and diabetic glucose loaded animals as well as normal off feed
animals. Confirmation of antidiabetic activity and toxicity ameliorative role of
S. cordata was investigated in a chronic multiple dose treatment study of fifteen
days. A single dose of alloxan (120 mg/kg) produced a decrease in insulin level,
hyperglycemia, elevated total lipids, triglycerides, and cholesterol and
decreased the high-density lipoproteins. Concurrent with these changes, there was
an increase in the concentration of lipid peroxidation (TBARS), H2O2, and nitrite
in pancreas, liver, and testis. This oxidative stress was related to a decrease
in glutathione content (GSH) and antioxidant enzymes. Administration of SCEE for
15 days after diabetes induction ameliorated hyperglycemia, restored lipid
profile, blunted the increase in TBARS, H2O2, and nitrite content, and stimulated
the GSH production in the organs of alloxan-treated rats. We suggested that SCEE
could be used as antidiabetic component in case of diabetes mellitus. This may be
related to its antioxidative properties.
PMID- 25114918
TI - Comparative study of corneal endothelial cell damage after femtosecond laser
assisted deep stromal dissection.
AB - PURPOSE: To find a relatively safe designed stromal bed thickness to avoid
endothelial damage for lamellar keratoplasty with an Allegretto Wavelight FS200
femtosecond laser. METHODS: Twelve rabbits were randomly divided into 50 MUm and
150 MUm groups according to the anticipated residue stromal bed thickness
preparation with a femtosecond laser. Six rabbits without laser cutting were used
as a control group. Central endothelial images were analyzed with in vivo
confocal microscopy and scanning electron microscopy. The apoptosis of
endothelium was evaluated with Hoechst 33342 staining and a TUNEL assay. RESULTS:
The endothelium of the 50 MUm group had extensive injuries upon in vivo confocal
and scanning electron microscopic observation, and minor injuries were observed
in the 150 MUm group. Moreover, more apoptotic cells were observed in the 50 MUm
group. CONCLUSIONS: When using a FS200 femtosecond laser assisted anterior
lamellar keratoplasty, there was minor endothelium damage with a 150 MUm stromal
bed, and a more than 150 MUm thickness stromal bed design may prevent the damage
of corneal endothelium.
PMID- 25114919
TI - Advances in miniaturized instruments for genomics.
AB - In recent years, a lot of demonstrations of the miniaturized instruments were
reported for genomic applications. They provided the advantages of
miniaturization, automation, sensitivity, and specificity for the development of
point-of-care diagnostics. The aim of this paper is to report on recent
developments on miniaturized instruments for genomic applications. Based on the
mature development of microfabrication, microfluidic systems have been
demonstrated for various genomic detections. Since one of the objectives of
miniaturized instruments is for the development of point-of-care device,
impedimetric detection is found to be a promising technique for this purpose. An
in-depth discussion of the impedimetric circuits and systems will be included to
provide total consideration of the miniaturized instruments and their potential
application towards real-time portable imaging in the "-omics" era. The current
excellent demonstrations suggest a solid foundation for the development of
practical and widespread point-of-care genomic diagnostic devices.
PMID- 25114917
TI - Gambling disorder during dopamine replacement treatment in Parkinson's disease: a
comprehensive review.
AB - Gambling Disorder (GD) is characterized by "the failure to resist gambling
impulses despite severe personal, family or occupational consequences". In the
fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM
V), GD replaces the DSM-IV diagnosis of Pathological Gambling (PG). GD estimated
prevalence ranges between 0.4% and 3.4% within the adult population and it seems
to be more common in patients with Parkinson's disease (PD). In this population,
GD recently has become more widely recognized as a possible complication of
dopamine agonist (DA) therapy. This association has aroused great interest for
the dramatic impact GD has on patients' quality of life. Management of PG in
patients with PD could be demanding. It is based on patient and caregiver
education, modification of dopamine replacement therapy, and in some cases
psychoactive drug administration. In this review article, the authors provide an
overview of GD pathogenesis during DA therapy as well as a summary of available
treatment options.
PMID- 25114920
TI - Exopolysaccharide from Ganoderma applanatum as a promising bioactive compound
with cytostatic and antibacterial properties.
AB - A new exopolysaccharide preparation isolated from stationary cultures of the
white rot fungus Ganoderma applanatum (GpEPS) was tested in terms of its
bioactive properties including its cytotoxic and immunostimulatory effect. The
results indicate that the tested GpEPS (at concentrations above 22.85 ug/mL and
228.5 ug/mL) may exhibit selective activity against tumor cells (cell lines SiHa)
and stimulate production of TNF-alpha THP-1-derived macrophages at the level of
752.17 pg/mL. The GpEPS showed antibacterial properties against Staphyloccoccus
aureus and a toxic effect against Vibrio fischeri cells (82.8% cell damage). High
cholesterol-binding capacity and triglycerides-binding capacity (57.9% and 41.6%
after 24 h of incubation with the tested substances, resp.) were also detected
for the investigated samples of GpEPS.
PMID- 25114922
TI - Modelling the aggregation process of cellular slime mold by the chemical
attraction.
AB - We put into exercise a comparatively innovative analytical modus operandi, the
homotopy decomposition method (HDM), for solving a system of nonlinear partial
differential equations arising in an attractor one-dimensional Keller-Segel
dynamics system. Numerical solutions are given and some properties show evidence
of biologically practical reliance on the parameter values. The reliability of
HDM and the reduction in computations give HDM a wider applicability.
PMID- 25114921
TI - Development of new method for simultaneous analysis of piracetam and
levetiracetam in pharmaceuticals and biological fluids: application in stability
studies.
AB - RP-HPLC ultraviolet detection simultaneous quantification of piracetam and
levetiracetam has been developed and validated. The chromatography was obtained
on a Nucleosil C18 column of 25 cm*0.46 cm, 10 MUm, dimension. The mobile phase
was a (70:30 v/v) mixture of 0.1 g/L of triethylamine and acetonitrile. Smooth
flow of mobile phase at 1 mL/min was set and 205 nm wavelength was selected.
Results were evaluated through statistical parameters which qualify the method
reproducibility and selectivity for the quantification of piracetam,
levetiracetam, and their impurities hence proving stability-indicating
properties. The proposed method is significantly important, permitting the
separation of the main constituent piracetam from levetiracetam. Linear behavior
was observed between 20 ng/mL and 10,000 ng/mL for both drugs. The proposed
method was checked in bulk drugs, dosage formulations, physiological condition,
and clinical investigations and excellent outcome was witnessed.
PMID- 25114923
TI - Biomechanics of interspinous devices.
AB - A number of interspinous devices (ISD) have been introduced in the lumbar spine
implant market. Unfortunately, the use of these devices often is not associated
with real comprehension of their biomechanical role. The aim of this paper is to
review the biomechanical studies about interspinous devices available in the
literature to allow the reader a better comprehension of the effects of these
devices on the treated segment and on the adjacent segments of the spine. For
this reason, our analysis will be limited to the interspinous devices that have
biomechanical studies published in the literature.
PMID- 25114924
TI - The trend in distribution of Q223R mutation of leptin receptor gene in amoebic
liver abscess patients from North India: a prospective study.
AB - Host genetic susceptibility is an important risk factor in infectious diseases.
We explored the distribution of Q223R mutation in leptin receptor gene of amoebic
liver abscess (ALA) patients of North India. A total of 55 ALA samples along with
102 controls were subjected to PCR-RFLP analysis. The frequency of allele "G"
(coding for arginine) was in general high in Indian population irrespective of
the disease. Our results of Fisher exact test shows that heterozygous mutant (QQ
versus QR, P=0.049) and homozygous mutant (QQ versus RR, P=0.004) were
significantly associated with amoebic liver abscess when compared with homozygous
wild (QQ).
PMID- 25114925
TI - Automated tissue classification framework for reproducible chronic wound
assessment.
AB - The aim of this paper was to develop a computer assisted tissue classification
(granulation, necrotic, and slough) scheme for chronic wound (CW) evaluation
using medical image processing and statistical machine learning techniques. The
red-green-blue (RGB) wound images grabbed by normal digital camera were first
transformed into HSI (hue, saturation, and intensity) color space and
subsequently the "S" component of HSI color channels was selected as it provided
higher contrast. Wound areas from 6 different types of CW were segmented from
whole images using fuzzy divergence based thresholding by minimizing edge
ambiguity. A set of color and textural features describing granulation, necrotic,
and slough tissues in the segmented wound area were extracted using various
mathematical techniques. Finally, statistical learning algorithms, namely,
Bayesian classification and support vector machine (SVM), were trained and tested
for wound tissue classification in different CW images. The performance of the
wound area segmentation protocol was further validated by ground truth images
labeled by clinical experts. It was observed that SVM with 3rd order polynomial
kernel provided the highest accuracies, that is, 86.94%, 90.47%, and 75.53%, for
classifying granulation, slough, and necrotic tissues, respectively. The proposed
automated tissue classification technique achieved the highest overall accuracy,
that is, 87.61%, with highest kappa statistic value (0.793).
PMID- 25114926
TI - GABAB receptors expressed in human aortic endothelial cells mediate intracellular
calcium concentration regulation and endothelial nitric oxide synthase
translocation.
AB - GABAB receptors regulate the intracellular Ca2+ concentration ([Ca2+]i) in a
number of cells (e.g., retina, airway epithelium and smooth muscle), but whether
they are expressed in vascular endothelial cells and similarly regulate the
[Ca2+]i is not known. The purpose of this study was to investigate the expression
of GABAB receptors, a subclass of receptors to the inhibitory neurotransmitter
gamma-aminobutyric acid (GABA), in cultured human aortic endothelial cells
(HAECs), and to explore if altering receptor activation modified [Ca2+]i and
endothelial nitric oxide synthase (eNOS) translocation. Real-time PCR, western
blots and immunofluorescence were used to determine the expression of GABAB1 and
GABAB2 in cultured HAECs. The effects of GABAB receptors on [Ca2+]i in cultured
HAECs were demonstrated using fluo-3. The influence of GABAB receptors on eNOS
translocation was assessed by immunocytochemistry. Both GABAB1 and GABAB2 mRNA
and protein were expressed in cultured HAECs, and the GABAB1 and GABAB2 proteins
were colocated in the cell membrane and cytoplasm. One hundred MUM baclofen
caused a transient increase of [Ca2+]i and eNOS translocation in cultured HAECs,
and the effects were attenuated by pretreatment with the selective GABAB receptor
antagonists CGP46381 and CGP55845. GABAB receptors are expressed in HAECs and
regulate the [Ca2+]i and eNOS translocation. Cultures of HAECs may be a useful in
vitro model for the study of GABAB receptors and vascular biology.
PMID- 25114927
TI - Butylidenephthalide blocks potassium channels and enhances basal tension in
isolated guinea-pig trachea.
AB - Butylidenephthalide (Bdph, 30~300 MUM), a constituent of Ligusticum chuanxiong
Hort., significantly enhanced tension in isolated guinea-pig trachea. In this
study, we investigate the mechanism(s) of Bdph-induced contraction in the tissue.
Isolated trachea was bathed in 5 mL of Krebs solution containing indomethacin (3
MUM), and its tension changes were isometrically recorded. Cromakalim (3 MUM), an
ATP-dependent K+ channel opener, significantly antagonized the Bdph-induced
enhancement of baseline tension. Bdph (300 MUM) also significantly antagonized
cromakalim-induced relaxation. Bdph (300 MUM) did not significantly influence the
antagonistic effects of glibenclamide (GBC, 1 MUM) and tetraethylammonium (TEA, 8
mM) against the cromakalim-induced relaxation. However, Bdph (300 MUM) and 4
aminopiridine (4-AP, 5 mM), a blocker of K v 1 family of K+ channels, in
combination significantly rightward shifted the log concentration-relaxation
curve of cromakalim. The antagonistic effect of the combination almost equals the
sum of the individual effects of Bdph and 4-AP, suggesting that the antagonistic
mechanism of Bdph may be similar to that of 4-AP. All calcium channel blockers
influenced neither the baseline tension nor antagonistic effect of Bdph against
cromakalim. In conclusion, Bdph may be similar to 4-AP, a blocker of K v 1 family
of K+ channels, to enhance the baseline tension of guinea-pig trachea.
PMID- 25114928
TI - Geodermatophilus poikilotrophi sp. nov.: a multitolerant actinomycete isolated
from dolomitic marble.
AB - A novel Gram-reaction-positive, aerobic actinobacterium, tolerant to mitomycin C,
heavy metals, metalloids, hydrogen peroxide, desiccation, and ionizing- and UV
radiation, designated G18T, was isolated from dolomitic marble collected from
outcrops in Samara (Namibia). The growth range was 15-35 degrees C, at pH 5.5-9.5
and in presence of 1% NaCl, forming greenish-black coloured colonies on GYM
Streptomyces agar. Chemotaxonomic and molecular characteristics of the isolate
matched those described for other representatives of the genus Geodermatophilus.
The peptidoglycan contained meso-diaminopimelic acid as diagnostic diaminoacid.
The main phospholipids were phosphatidylethanolamine, phosphatidylcholine,
phosphatidylinositol, and small amount of diphosphatidylglycerol. MK-9(H4) was
the dominant menaquinone and galactose was detected as diagnostic sugar. The
major cellular fatty acids were branched-chain saturated acids iso-C16:0 and iso
C15:0 and the unsaturated C17:1 omega8c and C16:1 omega7c. The 16S rRNA gene
showed 97.4-99.1% sequence identity with the other representatives of genus
Geodermatophilus. Based on phenotypic results and 16S rRNA gene sequence
analysis, strain G18T is proposed to represent a novel species, Geodermatophilus
poikilotrophi. Type strain is G18T (=DSM 44209T=CCUG 63018T). The INSDC accession
number is HF970583. The novel R software package lethal was used to compute the
lethal doses with confidence intervals resulting from tolerance experiments.
PMID- 25114929
TI - Ameliorative effect of saffron aqueous extract on hyperglycemia, hyperlipidemia,
and oxidative stress on diabetic encephalopathy in streptozotocin induced
experimental diabetes mellitus.
AB - Diabetic encephalopathy is one of the severe complications in patients with
diabetes mellitus. Findings indicate that saffron extract has antioxidant
properties but its underlying beneficial effects on diabetic encephalopathy were
unclear. In the present study, the protective activities of saffron were
evaluated in diabetic encephalopathy. Saffron at 40 and 80 mg/kg significantly
increased body weight and serum TNF-alpha and decreased blood glucose levels,
glycosylated serum proteins, and serum advanced glycation endproducts (AGEs)
levels. Furthermore, significant increase in HDL and decrease (P<0.05) in
cholesterol, triglyceride, and LDL were observed after 28 days of treatment. At
the end of experiments, the hippocampus tissue was used for determination of
glutathione content (GSH), superoxide dismutase (SOD), and catalase (CAT)
activities. Furthermore, saffron significantly increased GSH, SOD, and CAT but
remarkably decreased cognitive deficit, serum TNF-alpha, and induced nitric oxide
synthase (iNOS) activity in hippocampus tissue. Our findings indicated that
saffron extract may reduce hyperglycemia and hyperlipidemia risk and also reduce
the oxidative stress in diabetic encephalopathy rats. This study suggested that
saffron extract might be a promising candidate for the improvement of chemically
induced diabetes and its complications.
PMID- 25114930
TI - Acetylated hyaluronic acid: enhanced bioavailability and biological studies.
AB - Hyaluronic acid (HA), a macropolysaccharidic component of the extracellular
matrix, is common to most species and it is found in many sites of the human
body, including skin and soft tissue. Not only does HA play a variety of roles in
physiologic and in pathologic events, but it also has been extensively employed
in cosmetic and skin-care products as drug delivery agent or for several
biomedical applications. The most important limitations of HA are due to its
short half-life and quick degradation in vivo and its consequently poor
bioavailability. In the aim to overcome these difficulties, HA is generally
subjected to several chemical changes. In this paper we obtained an acetylated
form of HA with increased bioavailability with respect to the HA free form.
Furthermore, an improved radical scavenging and anti-inflammatory activity has
been evidenced, respectively, on ABTS radical cation and murine
monocyte/macrophage cell lines (J774.A1).
PMID- 25114931
TI - Integrated analysis identifies interaction patterns between small molecules and
pathways.
AB - Previous studies have indicated that the downstream proteins in a key pathway can
be potential drug targets and that the pathway can play an important role in the
action of drugs. So pathways could be considered as targets of small molecules. A
link map between small molecules and pathways was constructed using gene
expression profile, pathways, and gene expression of cancer cell line intervened
by small molecules and then we analysed the topological characteristics of the
link map. Three link patterns were identified based on different drug discovery
implications for breast, liver, and lung cancer. Furthermore, molecules that
significantly targeted the same pathways tended to treat the same diseases. These
results can provide a valuable reference for identifying drug candidates and
targets in molecularly targeted therapy.
PMID- 25114933
TI - Solid-nanoemulsion preconcentrate for oral delivery of paclitaxel: formulation
design, biodistribution, and gamma scintigraphy imaging.
AB - Aim of present study was to develop a solid nanoemulsion preconcentrate of
paclitaxel (PAC) using oil [propylene glycol monocaprylate/glycerol monooleate,
4:1 w/w], surfactant [polyoxyethylene 20 sorbitan monooleate/polyoxyl 15
hydroxystearate, 1:1 w/w], and cosurfactant [diethylene glycol monoethyl
ether/polyethylene glycol 300, 1:1 w/w] to form stable nanocarrier. The prepared
formulation was characterized for droplet size, polydispersity index, and zeta
potential. Transmission electron microscopy (TEM), differential scanning
calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared
spectroscopy (FTIR) were used to assess surface morphology and drug encapsulation
and its integrity. Cumulative drug release of prepared formulation through
dialysis bag and permeability coefficient through everted gut sac were found to
be remarkably higher than the pure drug suspension and commercial intravenous
product (Intaxel), respectively. Solid nanoemulsion preconcentrate of PAC
exhibited strong inhibitory effect on proliferation of MCF-7 cells in MTT assay.
In vivo systemic exposure of prepared formulation through oral administration was
comparable to that of Intaxel in gamma scintigraphy imaging. Our findings suggest
that the prepared solid nanoemulsion preconcentrate can be used as an effective
oral solid dosage form to improve dissolution and bioavailability of PAC.
PMID- 25114935
TI - Evaluation of medicine prescription pattern using World Health Organization
prescribing indicators in Iran: A cross-sectional study.
AB - OBJECTIVE: The objective was to quantify the specialists' prescription pattern in
Iran and to point out the prescribing behavioral differences among several
specialties. METHODS: A retrospective cross-sectional study was carried out on
the claim data. National prescription data were obtained on the basis of the
claims that the pharmacies submitted to the insurers during 1 year period of the
study. More than 85 million prescriptions were analyzed using "Rx-Analyst"
software that is designed and applied by National Committee of Rational Use of
Medicines in Iran. Specified medical specialties were considered and the World
Health Organization prescription indicators were used to evaluate the physicians'
prescribing behavior. FINDINGS: Average items per prescription were ranged from
3.68 in cardiologists' to 2.06 in dermatologists' prescriptions. The highest and
the lowest mean price were belonged to neurologists' and ophthalmologists'
prescriptions, respectively. In addition, 45% of patients received antibiotics,
41% of patients received injectable form of drugs, and 23% received
corticosteroids. A high tendency toward prescribing corticosteroids and
antibiotics as well as an injectable form of medicines was observed among general
physicians. CONCLUSION: There is an inevitable need to improve prescription
habits among different specialties, especially among general practitioners. This
causes the policymakers to put more emphasis on priorities such as continuous
education.
PMID- 25114934
TI - Simultaneous detection and differentiation of highly virulent and classical
Chinese-type isolation of PRRSV by real-time RT-PCR.
AB - Porcine reproductive and respiratory syndrome (PRRS) is a leading disease in pig
industry worldwide and can result in serious economic losses each year. The PRRS
epidemic situation in China has been very complicated since the unprecedented
large-scale highly pathogenic PRRS (HP-PRRS) outbreaks in 2006. And now the HP
PRRS virus (HP-PRRSV) and classical North American type PRRSV strains have
coexisted in China. Rapid differential detection of the two strains of PRRSV is
very important for effective PRRS control. The real-time RT-PCR for simultaneous
detection and differentiation of HP-PRRSV and PRRSV by using both SYBR Green and
TaqMan probes was developed and validated. Both assays can be used for rapid
detection and strain-specific identification of HP-PRRSV and PRRSV. However, the
TaqMan probe method had the highest detection rate whereas the conventional RT
PCR was the lowest. The real-time RT-PCR developed based on SYBR Green and TaqMan
probe could be used for simultaneous detection and differentiation of HP-PRRSV
and PRRSV in China, which will benefit much the PRRS control and research.
PMID- 25114936
TI - Identification and management of adverse effects of antipsychotics in a tertiary
care teaching hospital.
AB - OBJECTIVE: Antipsychotics have revolutionized psychiatry by allowing significant
numbers of patients in long-term hospital settings to be discharged and
successfully maintained in the community. However, these medications are also
associated with a range of adverse events ranging from mostly annoying to rarely
dangerous. This study is carried out to identify the adverse drug reactions
(ADRs) to antipsychotics and its management in psychiatric patients. METHODS:
Prospective interventional study was conducted in the psychiatric unit of a
tertiary care hospital. Patients of any age and either sex prescribed with at
least one antipsychotic were included and monitored for ADRs. FINDINGS: Among the
517 patients receiving antipsychotics, a total of 289 ADRs were identified from
217 patients at an overall incidence rate of 41.97%. Sixty-seven different kinds
of ADRs were observed in the study patients. Central and peripheral nervous
system was the most commonly affected system organ class (n = 59) and weight gain
(n = 30) was the most commonly observed ADR. Olanzapine was most commonly
implicated in reported ADRs (n = 92) followed by risperidone (n = 59). Of the 289
ADRs, 80% required interventions including cessation of drug and/or
specific/symptomatic/nonpharmacological treatment. CONCLUSION: This post
marketing surveillance study provides a representative data of the ADR profile of
the antipsychotics likely to be encountered in psychiatric patients in an Indian
tertiary care hospital.
PMID- 25114932
TI - Clinical study of nasopharyngeal carcinoma treated by helical tomotherapy in
China: 5-year outcomes.
AB - BACKGROUND: To evaluate the outcomes of nasopharyngeal carcinoma (NPC) patients
treated with helical tomotherapy (HT). METHODS: Between September 2007 and August
2012, 190 newly diagnosed NPC patients were treated with HT. Thirty-one patients
were treated with radiation therapy as single modality, 129 with additional
cisplatin-based chemotherapy with or without anti-EGFR monoclonal antibody
therapy, and 30 with concurrent anti-EGFR monoclonal antibody therapy. RESULTS:
Acute radiation related side effects were mainly grade 1 or 2. Grade 3 and
greater toxicities were rarely noted. The median followup was 32 (3-38) months.
The local relapse-free survival (LRFS), nodal relapse-free survival (NRFS),
distant metastasis-free survival (DMFS), and overall survival (OS) were 96.1%,
98.2%, 92.0%, and 86.3%, respectively, at 3 years. Cox multivariate regression
analysis showed that age and T stage were independent predictors for 3-year OS.
CONCLUSIONS: Helical tomotherapy for NPC patients achieved excellent 3-year
locoregional control, distant metastasis-free survival, and overall survival,
with relatively minor acute and late toxicities. Age and T stage were the main
prognosis factors.
PMID- 25114937
TI - Education alone is not enough in ventilator associated pneumonia care bundle
compliance.
AB - OBJECTIVE: Ventilator-associated pneumonia (VAP) described as a secondary and
preventable consequence in mechanically ventilated patients, emerges 48 h or more
after patients intubation. Considering the high morbidity and mortality rate of
VAP and the fact that VAP is preventable, it seemed necessary to evaluate care
bundle compliance rate and effect of education on its improvement. METHODS: This
observational study was conducted on 10 Intensive Care Units (ICUs) of four
university affiliated hospitals in three steps. In the first step, VAP care
bundle compliance including head of bed (HOB) elevation, endotracheal cuff
pressure (ETCP), mouthwash time, utilizing close suction systems, subglottic
secretion drainage, type of suction package, and hand wash before suctioning was
evaluated. In the second and third steps, ICU staffs were trained and its effect
on VAP care bundle compliance was investigated. Finally, an inquiry from nurses
was conducted to evaluate the obtained results. FINDINGS: A total of 552
checklists consisting of 294 observations in the pre-education group and 258
observations in the posteducation group were filled. Mean VAP care bundle
compliance in pre-education and posteducation stages was 36.5% and 41.2%,
respectively (P > 0.05). Except for patients' mouth washing, there were no
improvement in HOB elevation (>30 degrees ), hand washing and ETCP after
education. Based on the results of questionnaire received from nurses at the end
of study, more than 90% of nurses believed that lack of rigid monitoring of VAP
care bundle is a main reason of low adherence for VAP care bundle compliance.
CONCLUSION: The adherence to VAP care bundle was inappropriate. Education seems
to be ineffective on improving VAP care bundle compliance. Frequent recall of the
necessity of the VAP care bundle and the continuous supervision of ICU staffs is
highly recommended.
PMID- 25114938
TI - Assessing health conditions and medication use among the homeless community in
Long Beach, California.
AB - OBJECTIVE: Persons experiencing homelessness are a vulnerable population and are
at increased risk for morbidity and all-cause mortality compared to the general
population. This study sought to evaluate medication use, regular physician
visits, and identify health conditions among the homeless population of Long
Beach, California. METHODS: Two "brown bag" medication review events were held at
homeless shelters in the Long Beach area. Demographic information, medication
use, and comorbid disease states were obtained through surveys. FINDINGS: Three
fourths of the cohort (95 participants) consisted of males, and the average age
of participants was 48 years. Psychiatric disorders and cardiovascular disease
were the most common disease states reported at 32% and 46%, respectively and so
were medications used in treating these chronic diseases. Medication adherence
was found to be a significant problem in this population, where more than 30% of
patients were nonadherent to medications for chronic diseases. Furthermore, foot
problems, hearing and vision difficulties constitute the most commonly overlooked
health problems within the homeless population. CONCLUSION: Based on this and
other similar finding, we must accept that the homeless represent a vulnerable
population, and that because of this fact, more programs should be focused at
improving availability and access to health care among the homeless. Regarding
the high number of reported health problems in the study, more studies are needed
and more studies should incorporate screening for foot, hearing, and vision
issues, both to increase awareness and to provide an opportunity for devising
possible solutions to these highly preventable conditions.
PMID- 25114939
TI - Adherence to American society of health-system pharmacists surgical antibiotic
prophylaxis guidelines in a teaching hospital.
AB - OBJECTIVE: Surgical site infections are the second most common type of adverse
events occurring in hospitalized patients, whereas an estimated 40-60% of these
infections are thought to be preventable. Choice of regimen, administration
timing or duration of antibiotic prophylaxis is reported to be inappropriate in
approximately 25-50% of cases. We tried to evaluate an antibiotic administration
pattern for surgical antibiotic prophylaxis in a teaching hospital. METHODS: This
study was conducted at the general surgery and orthopedic wards of a teaching
hospital affiliated with Mazandaran University of Medical Sciences. The medical
records of admitted patients who underwent different surgical procedures were
reviewed. Compliance was assessed with the recommendations of the American
Society of Health-System Pharmacists' guidelines for every aspect of antibiotic
prophylaxis. All data were coded and analyzed by SPSS16 software using Student's
t-test and Chi-square test. FINDINGS: During 1 year, 759 patients who underwent
different surgeries were included in the study. Mean age of patients was 32.02 +/
18.79 years. Hand and foot fractures repair were the most frequent surgery
types. About 56.4% of administered prophylactic antibiotics were in accordance
with the American Society of Health System Pharmacists (ASHP) guidelines
regarding prophylaxis indication. The most commonly antibiotic used was cefazolin
and antibiotic choices were appropriate in 104 of 168 surgical procedures (62%).
Gentamicin, metronidazole and ceftriaxone were the most frequently antibiotics
that used inappropriately. Only in 100 of 168 procedures, duration was concordant
with the ASHP guideline, whereas in 68 procedures, duration was longer than
recommended time. In 98 procedures, the dose was lower and in one procedure, it
was higher than recommended doses. CONCLUSION: Although such guidelines have been
in place for many years, studies showed that much inappropriate antibiotic use as
prophylaxis and poor adherence to guidelines are still major issues. It is
essential for surgeons to be aware to consider the best antibiotic choices, dose
and duration based on reliable guidelines for antibiotic prophylaxis.
PMID- 25114940
TI - Efficacy of a local-drug delivery gel containing extracts of Quercus brantii and
Coriandrum sativum as an adjunct to scaling and root planing in moderate chronic
periodontitis patients.
AB - OBJECTIVE: Recent advances in the field of alternative medicine introduced
various herbal products for the treatment of periodontitis. The purpose of this
study was to evaluate the effects of combined extracts from Quercus brantii and
Coriandrum sativum on periodontal indices in adult periodontitis patients.
METHODS: In this randomized, double-blinded clinical trial, performed in Isfahan
Dental School in 2012, a new herbal medicament containing combined extracts from
Q. brantii and C. sativum was formulated in the gel form for subgingival
application. Following scaling and root planing (SRP), both herbal and placebo
gels were delivered at the experimental and control sites, respectively.
Periodontal pocket depth, clinical attachment level, papilla bleeding index, and
plaque index were measured at baseline, 1 month and 3 months later. Both intra
and inter-groups changes were registered. The obtained data were analyzed by SPSS
software, using repeated measure analysis of variance, paired t-test, Mann
Whitney, Friedman, and Wilcoxon tests. Differences with P < 0.05 were considered
to be significant. FINDINGS: Both groups indicated statistically significant
improvements in the periodontal indices (P < 0.05), but there were no significant
differences between two study groups with this regard. CONCLUSION: The herbal gel
does not have considerable advantages over SRP alone as an adjunct in periodontal
treatment.
PMID- 25114941
TI - Ceftriaxone induced drug rash with eosinophilia and systemic symptoms.
AB - Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a drug
reaction commonly occurring in association with aromatic anticonvulsants and
allopurinol. It is characterized by triad of fever, skin eruption, and systemic
involvement. DRESS is rare with beta-lactam antibiotics and even rarer with
ceftriaxone. We describe a case of pneumonia who developed ceftriaxone-induced
rash, bicytopenia, eosinophilia, transaminitis and was eventually diagnosed and
managed successfully as a case of DRESS.
PMID- 25114942
TI - Nudging by shaming, shaming by nudging.
PMID- 25114943
TI - Harnessing the potential to quantify public preferences for healthcare priorities
through citizens' juries.
AB - Despite progress towards greater public engagement, questions about the optimal
approach to access public preferences remain unanswered. We review two
increasingly popular methods for engaging the public in healthcare priority
setting and determining their preferences; the Citizens' Jury (CJ) and Discrete
Choice Experiment (DCE). We discuss the theoretical framework from which each
method is derived, its application in healthcare, and critique the information it
can provide for decision-makers. We conclude that combining deliberation of an
informed public via CJs and quantification of preferences using DCE methods,
whilst it remains to be tested as an approach to engaging the public in priority
setting, could potentially achieve much richer information than the application
of either method in isolation.
PMID- 25114944
TI - Factors affecting the technical efficiency of health systems: A case study of
Economic Cooperation Organization (ECO) countries (2004-10).
AB - BACKGROUND: Improving efficiency of health sector is of particular importance in
all countries. To reach this end, it is paramount to measure the efficiency. On
the other hand, there are many factors that affect the efficiency of health
systems. This study aimed to measure the Technical Efficiency (TE) of health
systems in Economic Cooperation Organization (ECO) countries during 2004-10 and
to determine the factors affecting their TE. METHODS: This was a descriptive
analytical and panel study. The required data were gathered using library and
field studies, available statistics and international websites through completing
data collection forms. In this study, the TE of health systems in 10 ECO
countries was measured using their available data and Data Envelopment Analysis
(DEA) through two approaches. The first approach used GDP per capita, education
and smoking as its inputs and life expectancy and infant mortality rates as the
outputs. The second approach, also, used the health expenditures per capita, the
number of physicians per thousand people, and the number of hospital beds per
thousand people as its inputs and life expectancy and under-5 mortality rates as
the outputs. Then, the factors affecting the TE of health systems were determined
using the panel data logit model. Excel 2010, Win4Deap 1.1.2 and Stata 11.0 were
used to analyze the collected data. RESULTS: According to the first approach, the
mean TE of health systems was 0.497 and based on the second one it was 0.563.
Turkey and Turkmenistan had, respectively, the highest and lowest mean of
efficiency. Also, the results of panel data logit model showed that only GDP per
capita and health expenditures per capita had significant relationships with the
TE of health systems. CONCLUSION: In order to maximize the TE of health systems,
health policy-makers should pay special attention to the proper use of healthcare
resources according to the people's needs, the appropriate management of the
health system resources, allocating adequate budgets to the health sector,
establishing an appropriate referral system to provide better public access to
health services according to their income and needs, among many others.
PMID- 25114945
TI - Prevalence and determinants of under-nutrition among children under six: a cross
sectional survey in Fars province, Iran.
AB - BACKGROUND: Childhood malnutrition as a major public health problem among
children in developing countries can affect physical and intellectual growth and
is also considered as a main cause of child morbidity and mortality. The
objective of this study was to estimate the prevalence of under-nutrition and
identify determinants of malnutrition among children under 6 years of age in Fars
province, Iran. METHODS: This survey was conducted by house to house visit
through multi-stage sampling in 30 cities of Fars province, during December 2012
to January 2013. A total of 15408 children, aged 0-6 years old, were studied for
nutritional assessment in terms of underweight, stunting, and wasting. Also,
socio-demographic measures were obtained from structured questionnaire. Backward
stepwise logistic regression was used to relate underlying factors to the odds of
under-nutrition indices. RESULTS: The rates of stunting, underweight, and wasting
were 9.53, 9.66, and 8.19%, respectively. Male children were more stunted
compared to females (OR= 1.41, CI: 1.26-1.58). Also, stunting was significantly
associated with lower family income (OR= 3.21, CI: 1.17-8.85) and lower maternal
education (OR= 0.80, CI: 0.64-0.98). Living in urban areas, and poor water supply
were identified as significant risk factors of all three types of childhood under
nutrition. Moreover, Khamse and Arab ethnic groups were more vulnerable to under
nutrition. There was a suggestion that non-access to health services were
associated with wasting (OR= 1.87, CI: 1.39-2.52) and also large family size was
related to underweight (OR= 1.35, CI: 1.10-1.65). CONCLUSION: The prevalence of
under-nutrition in the study population was categorized in low levels. However,
planning the public preventive strategies can help to control childhood under
nutrition according to underlying factors of malnutrition in the study population
including gender, settlement area, family size, ethnicity, family income,
maternal education, health services, and also safe water supply.
PMID- 25114946
TI - Factors influencing healthcare service quality.
AB - BACKGROUND: The main purpose of this study was to identify factors that influence
healthcare quality in the Iranian context. METHODS: Exploratory in-depth
individual and focus group interviews were conducted with 222 healthcare
stakeholders including healthcare providers, managers, policy-makers, and payers
to identify factors affecting the quality of healthcare services provided in
Iranian healthcare organisations. RESULTS: Quality in healthcare is a production
of cooperation between the patient and the healthcare provider in a supportive
environment. Personal factors of the provider and the patient, and factors
pertaining to the healthcare organisation, healthcare system, and the broader
environment affect healthcare service quality. Healthcare quality can be improved
by supportive visionary leadership, proper planning, education and training,
availability of resources, effective management of resources, employees and
processes, and collaboration and cooperation among providers. CONCLUSION: This
article contributes to healthcare theory and practice by developing a conceptual
framework that provides policy-makers and managers a practical understanding of
factors that affect healthcare service quality.
PMID- 25114947
TI - Technical efficiency of teaching hospitals in Iran: the use of Stochastic
Frontier Analysis, 1999-2011.
AB - BACKGROUND: Hospitals are highly resource-dependent settings, which spend a large
proportion of healthcare financial resources. The analysis of hospital efficiency
can provide insight into how scarce resources are used to create health values.
This study examines the Technical Efficiency (TE) of 12 teaching hospitals
affiliated with Tehran University of Medical Sciences (TUMS) between 1999 and
2011. METHODS: The Stochastic Frontier Analysis (SFA) method was applied to
estimate the efficiency of TUMS hospitals. A best function, referred to as output
and input parameters, was calculated for the hospitals. Number of medical
doctors, nurses, and other personnel, active beds, and outpatient admissions were
considered as the input variables and number of inpatient admissions as an output
variable. RESULTS: The mean level of TE was 59% (ranging from 22 to 81%). During
the study period the efficiency increased from 61 to 71%. Outpatient admission,
other personnel and medical doctors significantly and positively affected the
production (P< 0.05). Concerning the Constant Return to Scale (CRS), an optimal
production scale was found, implying that the productions of the hospitals were
approximately constant. CONCLUSION: Findings of this study show a remarkable
waste of resources in the TUMS hospital during the decade considered. This
warrants policy-makers and top management in TUMS to consider steps to improve
the financial management of the university hospitals.
PMID- 25114948
TI - Addressing diabetes at the crossroads of global pandemic and regional culture:
Comment on "The curse of wealth - Middle Eastern countries need to address the
rapidly rising burden of diabetes".
AB - As diabetes and obesity rates continue to climb at astronomical rates in the
Middle East, future generations are at an even greater risk for diabetes and the
associated complications. Many factors are at play and it is clear that creative
solutions are needed to retool provider resources in the Middle East towards
prevention of diabetes and its complications while leveraging technology to
maximize outreach within the accepted cultural norms. Only by building the
capacity to address the current diabetes burden as well focusing on prevention
for the future, can Middle East countries create a strong infrastructure for a
successful future.
PMID- 25114949
TI - Global health politics: neither solidarity nor policy: Comment on "Globalization
and the diffusion of ideas: why we should acknowledge the roots of mainstream
ideas in global health".
AB - The global health agenda has been dominating the current global health policy
debate. Furthermore, it has compelled countries to embrace strategies for
tackling health inequalities in a wide range of public health areas. The article
by Robert and colleagues highlights that although globalization has increased
opportunities to share and spread ideas, there is still great asymmetry of power
according to the countries' economic and political development. It also
emphasizes how policy diffusion from High Income Countries (HICs) to Low- and
Middle-Income Countries (LMICs) have had flaws at understanding their political,
economic, and cultural backgrounds while they are pursuing knowledge translation.
Achieving a fair global health policy diffusion of ideas would imply a call for a
renewal on political elites worldwide at coping global health politics.
Accordingly, moving towards fairness in disseminating global health ideas should
be driven by politics not only as one of the social determinants of health, but
the main determinant of health and well-being among-and within-societies.
PMID- 25114950
TI - The search for underlying principles of health impact assessment: progress and
prospects: Comment on "Investigating underlying principles to guide health impact
assessment".
AB - Health Impact Assessment (HIA) is a relatively young field of endeavour, and
hence, future progress will depend on the planning, implementation and rigorous
evaluation of additional HIAs of projects, programmes and policies the world
over. In the June 2014 issue of the International Journal of Health Policy and
Management, Fakhri and colleagues investigated underlying principles of HIA
through a comprehensive review of the literature and expert consultation. With an
emphasis on the Islamic Republic of Iran, the authors identified multiple issues
that are relevant for guiding HIA practice. At the same time, the study
unravelled current shortcomings in the understanding and definition of HIA
principles and best practice at national, regional, and global levels. In this
commentary we scrutinise the research presented, highlight strengths and
limitations, and discuss the findings in the context of other recent attempts to
guide HIA.
PMID- 25114951
TI - Global health diplomacy: a 'Deus ex Machina' for international development and
relations: Comment on "A Ghost in the Machine? Politics in Global Health Policy".
PMID- 25114953
TI - Gas production strategy of underground coal gasification based on multiple gas
sources.
AB - To lower stability requirement of gas production in UCG (underground coal
gasification), create better space and opportunities of development for UCG, an
emerging sunrise industry, in its initial stage, and reduce the emission of blast
furnace gas, converter gas, and coke oven gas, this paper, for the first time,
puts forward a new mode of utilization of multiple gas sources mainly including
ground gasifier gas, UCG gas, blast furnace gas, converter gas, and coke oven gas
and the new mode was demonstrated by field tests. According to the field tests,
the existing power generation technology can fully adapt to situation of high
hydrogen, low calorific value, and gas output fluctuation in the gas production
in UCG in multiple-gas-sources power generation; there are large fluctuations and
air can serve as a gasifying agent; the gas production of UCG in the mode of both
power and methanol based on multiple gas sources has a strict requirement for
stability. It was demonstrated by the field tests that the fluctuations in gas
production in UCG can be well monitored through a quality control chart method.
PMID- 25114954
TI - Free convection nanofluid flow in the stagnation-point region of a three
dimensional body.
AB - Analytical results are presented for a steady three-dimensional free convection
flow in the stagnation point region over a general curved isothermal surface
placed in a nanofluid. The momentum equations in x- and y-directions, energy
balance equation, and nanoparticle concentration equation are reduced to a set of
four fully coupled nonlinear differential equations under appropriate similarity
transformations. The well known technique optimal homotopy analysis method (OHAM)
is used to obtain the exact solution explicitly, whose convergence is then
checked in detail. Besides, the effects of the physical parameters, such as the
Lewis number, the Brownian motion parameter, the thermophoresis parameter, and
the buoyancy ratio on the profiles of velocities, temperature, and concentration,
are studied and discussed. Furthermore the local skin friction coefficients in x-
and y-directions, the local Nusselt number, and the local Sherwood number are
examined for various values of the physical parameters.
PMID- 25114952
TI - Andrographolide inhibits nuclear factor-kappaB activation through JNK-Akt-p65
signaling cascade in tumor necrosis factor-alpha-stimulated vascular smooth
muscle cells.
AB - Critical vascular inflammation leads to vascular dysfunction and cardiovascular
diseases, including abdominal aortic aneurysms, hypertension, and
atherosclerosis. Andrographolide is the most active and critical constituent
isolated from the leaves of Andrographis paniculata, a herbal medicine widely
used for treating anti-inflammation in Asia. In this study, we investigated the
mechanisms of the inhibitory effects of andrographolide in vascular smooth muscle
cells (VSMCs) exposed to a proinflammatory stimulus, tumor necrosis factor-alpha
(TNF-alpha). Treating TNF-alpha-stimulated VSMCs with andrographolide suppressed
the expression of inducible nitric oxide synthase in a concentration-dependent
manner. A reduction in TNF-alpha-induced c-Jun N-terminal kinase (JNK), Akt, and
p65 phosphorylation was observed in andrographolide-treated VSMCs. However,
andrographolide affected neither IkappaBalpha degradation nor p38 mitogen
activated protein kinase or extracellular signal-regulated kinase 1/2
phosphorylation under these conditions. Both treatment with LY294002, a
phosphatidylinositol 3-kinase/Akt inhibitor, and treatment with SP600125, a JNK
inhibitor, markedly reversed the andrographolide-mediated inhibition of p65
phosphorylation. In addition, LY294002 and SP600125 both diminished Akt
phosphorylation, whereas LY294002 had no effects on JNK phosphorylation. These
results collectively suggest that therapeutic interventions using andrographolide
can benefit the treatment of vascular inflammatory diseases, and andrographolide
mediated inhibition of NF-kappaB activity in TNF-alpha-stimulated VSMCs occurs
through the JNK-Akt-p65 signaling cascade, an IkappaBalpha-independent mechanism.
PMID- 25114955
TI - Moving object localization using optical flow for pedestrian detection from a
moving vehicle.
AB - This paper presents a pedestrian detection method from a moving vehicle using
optical flows and histogram of oriented gradients (HOG). A moving object is
extracted from the relative motion by segmenting the region representing the same
optical flows after compensating the egomotion of the camera. To obtain the
optical flow, two consecutive images are divided into grid cells 14 * 14 pixels;
then each cell is tracked in the current frame to find corresponding cell in the
next frame. Using at least three corresponding cells, affine transformation is
performed according to each corresponding cell in the consecutive images, so that
conformed optical flows are extracted. The regions of moving object are detected
as transformed objects, which are different from the previously registered
background. Morphological process is applied to get the candidate human regions.
In order to recognize the object, the HOG features are extracted on the candidate
region and classified using linear support vector machine (SVM). The HOG feature
vectors are used as input of linear SVM to classify the given input into
pedestrian/nonpedestrian. The proposed method was tested in a moving vehicle and
also confirmed through experiments using pedestrian dataset. It shows a
significant improvement compared with original HOG using ETHZ pedestrian dataset.
PMID- 25114956
TI - Changes in stream peak flow and regulation in Naoli River watershed as a result
of wetland loss.
AB - Hydrology helps determine the character of wetlands; wetlands, in turn, regulate
water flow, which influences regional hydrology. To understand these dynamics, we
studied the Naoli basin where, from 1954 to 2005, intensive marshland cultivation
took place, and the watershed's wetland area declined from 94.4 * 10(4)ha to 17.8
* 10(4)ha. More than 80% of the wetland area loss was due to conversion to
farmland, especially from 1976 to 1986. The processes of transforming wetlands to
cultivated land in the whole Naoli basin and subbasins can be described using a
first order exponential decay model. To quantify the effects of wetlands
cultivation, we analyzed daily rainfall and streamflow data measured from 1955 to
2005 at two stations (Baoqing Station and Caizuizi Station). We defined a
streamflow regulation index (SRI) and applied a Mann-Kendall-Sneyers test to
further analyze the data. As the wetland area decreased, the peak streamflow at
the Caizuizi station increased, and less precipitation generated heavier peak
flows, as the runoff was faster than before. The SRI from 1959 to 2005 showed an
increasing trend; the SRI rate of increase was 0.05/10a, demonstrating that the
watershed's regulation of streamflow regulation was declined as the wetlands
disappeared.
PMID- 25114957
TI - Fractal analysis of laplacian pyramidal filters applied to segmentation of soil
images.
AB - The laplacian pyramid is a well-known technique for image processing in which
local operators of many scales, but identical shape, serve as the basis
functions. The required properties to the pyramidal filter produce a family of
filters, which is unipara metrical in the case of the classical problem, when the
length of the filter is 5. We pay attention to gaussian and fractal behaviour of
these basis functions (or filters), and we determine the gaussian and fractal
ranges in the case of single parameter a. These fractal filters loose less energy
in every step of the laplacian pyramid, and we apply this property to get
threshold values for segmenting soil images, and then evaluate their porosity.
Also, we evaluate our results by comparing them with the Otsu algorithm threshold
values, and conclude that our algorithm produce reliable test results.
PMID- 25114958
TI - Real-time safety risk assessment based on a real-time location system for
hydropower construction sites.
AB - The concern for workers' safety in construction industry is reflected in many
studies focusing on static safety risk identification and assessment. However,
studies on real-time safety risk assessment aimed at reducing uncertainty and
supporting quick response are rare. A method for real-time safety risk assessment
(RTSRA) to implement a dynamic evaluation of worker safety states on construction
site has been proposed in this paper. The method provides construction managers
who are in charge of safety with more abundant information to reduce the
uncertainty of the site. A quantitative calculation formula, integrating the
influence of static and dynamic hazards and that of safety supervisors, is
established to link the safety risk of workers with the locations of on-site
assets. By employing the hidden Markov model (HMM), the RTSRA provides a
mechanism for processing location data provided by the real-time location system
(RTLS) and analyzing the probability distributions of different states in terms
of false positives and negatives. Simulation analysis demonstrated the logic of
the proposed method and how it works. Application case shows that the proposed
RTSRA is both feasible and effective in managing construction project safety
concerns.
PMID- 25114959
TI - A high-speed and low-offset dynamic latch comparator.
AB - Circuit intricacy, speed, low-offset voltage, and resolution are essential
factors for high-speed applications like analog-to-digital converters (ADCs). The
comparator circuit with preamplifier increases the power dissipation, as it
requires higher amount of currents than the latch circuitry. In this research, a
novel topology of dynamic latch comparator is illustrated, which is able to
provide high speed, low offset, and high resolution. Moreover, the circuit is
able to reduce the power dissipation as the topology is based on latch circuitry.
The cross-coupled circuit mechanism with the regenerative latch is employed for
enhancing the dynamic latch comparator performance. In addition, input-tracking
phase is used to reduce the offset voltage. The Monte-Carlo simulation results
for the designed comparator in 0.18 MUm CMOS process show that the equivalent
input-referred offset voltage is 720 MUV with 3.44 mV standard deviation. The
simulated result shows that the designed comparator has 8-bit resolution and
dissipates 158.5 MUW of power under 1.8 V supply while operating with a clock
frequency of 50 MHz. In addition, the proposed dynamic latch comparator has a
layout size of 148.80 MUm * 59.70 MUm.
PMID- 25114960
TI - Cytotoxic activities of flavonoids from Centaurea scoparia.
AB - Phytochemical studies on the ethanolic extract of the aerial parts of Centaurea
scoparia led to the isolation of two new flavonoids, 3',4'-dihydroxy-(3'',4''
dihydro-3''-hydroxy-4''-acetoxy)-2'',2''-dimethylpyrano-(5'',6'':7,8)-flavone-3-O
beta -D-glucopyranoside (1) and 3,3',4'-trihydroxy-(3'',4''-dihydro-3'',4''
dihydroxy)-2'',2''-dimethylpyrano-(5'',6'':7,8)-flavone (2), along with eight
known flavonoids isolated for the first time from this plant, cynaroside (3),
Apigetrin (4), centaureidin (5), oroxylin A (6), 5,7-dihydroxy-3',4',5'
trimethoxyflavone (7), atalantoflavone (8), 5-hydroxy-3',4',8-trimethoxy-2'',2''
dimethylpyrano (5'',6'':6,7)-flavone (9), and 3',4',5,8-tetramethoxy-2'',2''
dimethylpyrano (5'',6'':6,7)-flavone (10). The structures of the isolated
compounds were elucidated by means of spectroscopic tools including 1D and 2D
NMR, UV, IR, and mass spectroscopy. Cytotoxic activities of the isolated
compounds were evaluated against human cervical carcinoma HeLa, human
hepatocellular carcinoma HepG2, and human breast carcinoma MCF-7. Compound 2 was
the most potent cytotoxic agent against HeLa cells with an IC50 0.079 MUM.
PMID- 25114961
TI - Research on radiation characteristic of plasma antenna through FDTD method.
AB - The radiation characteristic of plasma antenna is investigated by using the
finite-difference time-domain (FDTD) approach in this paper. Through using FDTD
method, we study the propagation of electromagnetic wave in free space in
stretched coordinate. And the iterative equations of Maxwell equation are
derived. In order to validate the correctness of this method, we simulate the
process of electromagnetic wave propagating in free space. Results show that
electromagnetic wave spreads out around the signal source and can be absorbed by
the perfectly matched layer (PML). Otherwise, we study the propagation of
electromagnetic wave in plasma by using the Boltzmann-Maxwell theory. In order to
verify this theory, the whole process of electromagnetic wave propagating in
plasma under one-dimension case is simulated. Results show that Boltzmann-Maxwell
theory can be used to explain the phenomenon of electromagnetic wave propagating
in plasma. Finally, the two-dimensional simulation model of plasma antenna is
established under the cylindrical coordinate. And the near-field and far-field
radiation pattern of plasma antenna are obtained. The experiments show that the
variation of electron density can introduce the change of radiation
characteristic.
PMID- 25114962
TI - Toughness condition for a graph to be a fractional (g, f, n)-critical deleted
graph.
AB - A graph G is called a fractional (g, f)-deleted graph if G - {e} admits a
fractional (g, f)-factor for any e ? E(G). A graph G is called a fractional (g,
f, n)-critical deleted graph if, after deleting any n vertices from G, the
resulting graph is still a fractional (g, f)-deleted graph. The toughness, as the
parameter for measuring the vulnerability of communication networks, has received
significant attention in computer science. In this paper, we present the
relationship between toughness and fractional (g, f, n)-critical deleted graphs.
It is determined that G is fractional (g, f, n)-critical deleted if t(G) >= ((b
(2) - 1 + bn)/a).
PMID- 25114963
TI - Riemann boundary value problem for triharmonic equation in higher space.
AB - We mainly deal with the boundary value problem for triharmonic function with
value in a universal Clifford algebra: Delta(3)[u](x) = 0, x ? R (n)??Omega, u
(+)(x) = u (-)(x)G(x) + g(x), x ? ?Omega, (D (j) u)(+)(x) = (D (j) u)(-)(x)A j +
f j (x), x ? ?Omega, u(infinity) = 0, where (j = 1,..., 5) ?Omega is a Lyapunov
surface in R (n) , D = ? k=1 (n) e k (?/?x k) is the Dirac operator, and u(x) = ?
A e A u A (x) are unknown functions with values in a universal Clifford algebra
Cl(V n,n). Under some hypotheses, it is proved that the boundary value problem
has a unique solution.
PMID- 25114965
TI - A novel clustering algorithm for mobile ad hoc networks based on determination of
virtual links' weight to increase network stability.
AB - The stability of clusters is a serious issue in mobile ad hoc networks. Low
stability of clusters may lead to rapid failure of clusters, high energy
consumption for reclustering, and decrease in the overall network stability in
mobile ad hoc network. In order to improve the stability of clusters, weight
based clustering algorithms are utilized. However, these algorithms only use
limited features of the nodes. Thus, they decrease the weight accuracy in
determining node's competency and lead to incorrect selection of cluster heads. A
new weight-based algorithm presented in this paper not only determines node's
weight using its own features, but also considers the direct effect of feature of
adjacent nodes. It determines the weight of virtual links between nodes and the
effect of the weights on determining node's final weight. By using this strategy,
the highest weight is assigned to the best choices for being the cluster heads
and the accuracy of nodes selection increases. The performance of new algorithm
is analyzed by using computer simulation. The results show that produced clusters
have longer lifetime and higher stability. Mathematical simulation shows that
this algorithm has high availability in case of failure.
PMID- 25114964
TI - Forest fire smoke layers observed in the free troposphere over Portugal with a
multiwavelength Raman lidar: optical and microphysical properties.
AB - Vertically resolved optical and microphysical properties of biomass burning
aerosols, measured in 2011 with a multiwavelength Raman lidar, are presented. The
transportation time, within 1-2 days (or less), pointed towards the presence of
relatively fresh smoke particles over the site. Some strong layers aloft were
observed with particle backscatter and extinction coefficients (at 355 nm)
greater than 5 Mm(-1)sr(-1) and close to 300 Mm(-1), respectively. The particle
intensive optical properties showed features different from the ones reported for
aged smoke, but rather consistent with fresh smoke. The Angstrom exponents were
generally high, mainly above 1.4, indicating a dominating accumulation mode. Weak
depolarization values, as shown by the small depolarization ratio of 5% or lower,
were measured. Furthermore, the lidar ratio presented no clear wavelength
dependency. The inversion of the lidar signals provided a set of microphysical
properties including particle effective radius below 0.2 MUm, which is less than
values previously observed for aged smoke particles. Real and imaginary parts of
refractive index of about 1.5-1.6 and 0.02i, respectively, were derived. The
single scattering albedo was in the range between 0.85 and 0.93; these last two
quantities indicate the nonnegligible absorbing characteristics of the observed
particles.
PMID- 25114966
TI - Combining digital watermarking and fingerprinting techniques to identify
copyrights for color images.
AB - This paper presents a copyright identification scheme for color images that takes
advantage of the complementary nature of watermarking and fingerprinting. It
utilizes an authentication logo and the extracted features of the host image to
generate a fingerprint, which is then stored in a database and also embedded in
the host image to produce a watermarked image. When a dispute over the copyright
of a suspect image occurs, the image is first processed by watermarking. If the
watermark can be retrieved from the suspect image, the copyright can then be
confirmed; otherwise, the watermark then serves as the fingerprint and is
processed by fingerprinting. If a match in the fingerprint database is found,
then the suspect image will be considered a duplicated one. Because the proposed
scheme utilizes both watermarking and fingerprinting, it is more robust than
those that only adopt watermarking, and it can also obtain the preliminary result
more quickly than those that only utilize fingerprinting. The experimental
results show that when the watermarked image suffers slight attacks, watermarking
alone is enough to identify the copyright. The results also show that when the
watermarked image suffers heavy attacks that render watermarking incompetent,
fingerprinting can successfully identify the copyright, hence demonstrating the
effectiveness of the proposed scheme.
PMID- 25114967
TI - A procedure for extending input selection algorithms to low quality data in
modelling problems with application to the automatic grading of uploaded
assignments.
AB - When selecting relevant inputs in modeling problems with low quality data, the
ranking of the most informative inputs is also uncertain. In this paper, this
issue is addressed through a new procedure that allows the extending of different
crisp feature selection algorithms to vague data. The partial knowledge about the
ordinal of each feature is modelled by means of a possibility distribution, and a
ranking is hereby applied to sort these distributions. It will be shown that this
technique makes the most use of the available information in some vague datasets.
The approach is demonstrated in a real-world application. In the context of
massive online computer science courses, methods are sought for automatically
providing the student with a qualification through code metrics. Feature
selection methods are used to find the metrics involved in the most meaningful
predictions. In this study, 800 source code files, collected and revised by the
authors in classroom Computer Science lectures taught between 2013 and 2014, are
analyzed with the proposed technique, and the most relevant metrics for the
automatic grading task are discussed.
PMID- 25114969
TI - SER performance of enhanced spatial multiplexing codes with ZF/MRC receiver in
time-varying Rayleigh fading channels.
AB - We propose enhanced spatial multiplexing codes (E-SMCs) to enable various
encoding rates. The symbol error rate (SER) performance of the E-SMC is
investigated when zero-forcing (ZF) and maximal-ratio combining (MRC) techniques
are used at a receiver. The proposed E-SMC allows a transmitted symbol to be
repeated over time to achieve further diversity gain at the cost of the encoding
rate. With the spatial correlation between transmit antennas, SER equations for M
ary QAM and PSK constellations are derived by using a moment generating function
(MGF) approximation of a signal-to-noise ratio (SNR), based on the assumption of
independent zero-forced SNRs. Analytic and simulated results are compared for
time-varying and spatially correlated Rayleigh fading channels that are modelled
as first-order Markovian channels. Furthermore, we can find an optimal block
length for the E-SMC that meets a required SER.
PMID- 25114968
TI - Exploring a QoS driven scheduling approach for peer-to-peer live streaming
systems with network coding.
AB - Most large-scale peer-to-peer (P2P) live streaming systems use mesh to organize
peers and leverage pull scheduling to transmit packets for providing robustness
in dynamic environment. The pull scheduling brings large packet delay. Network
coding makes the push scheduling feasible in mesh P2P live streaming and improves
the efficiency. However, it may also introduce some extra delays and coding
computational overhead. To improve the packet delay, streaming quality, and
coding overhead, in this paper are as follows. we propose a QoS driven push
scheduling approach. The main contributions of this paper are: (i) We introduce a
new network coding method to increase the content diversity and reduce the
complexity of scheduling; (ii) we formulate the push scheduling as an
optimization problem and transform it to a min-cost flow problem for solving it
in polynomial time; (iii) we propose a push scheduling algorithm to reduce the
coding overhead and do extensive experiments to validate the effectiveness of our
approach. Compared with previous approaches, the simulation results demonstrate
that packet delay, continuity index, and coding ratio of our system can be
significantly improved, especially in dynamic environments.
PMID- 25114971
TI - Combinatorial efficiency evaluation: the knapsack problem in data envelopment
analysis.
AB - The traditional data envelopment analysis (DEA) literatures generally
concentrated on the efficiency evaluation of single decision making unit (DMU).
However, in many practical problems, the decision makers are required to choose a
number of DMUs instead of a single one from the DMUs set. Therefore, it is
necessary to study the combinatorial efficiency evaluation problem which can be
illustrated as a knapsack problem naturally. It is indicated that the basic model
proposed by Cook and Green may have some drawbacks and a modified model, which is
combined with the super efficiency model, is proposed in this paper. What is
more, our proposed model is more persuasive to the decision makers because it is
able to provide a unique best combination of DMUs. An adapted local search
algorithm is developed as a solver of this problem. Finally, numerical examples
are provided to examine the validity of our proposed model and the adapted local
search algorithm.
PMID- 25114973
TI - Potential rainwater harvesting improvement using advanced remote sensing
applications.
AB - The amount of water on earth is the same and only the distribution and the
reallocation of water forms are altered in both time and space. To improve the
rainwater harvesting a better understanding of the hydrological cycle is
mandatory. Clouds are major component of the hydrological cycle; therefore,
clouds distribution is the keystone of better rainwater harvesting. Remote
sensing technology has shown robust capabilities in resolving challenges of water
resource management in arid environments. Soil moisture content and cloud average
distribution are essential remote sensing applications in extracting information
of geophysical, geomorphological, and meteorological interest from satellite
images. Current research study aimed to map the soil moisture content using
recent Landsat 8 images and to map cloud average distribution of the
corresponding area using 59 MERIS satellite imageries collected from January 2006
to October 2011. Cloud average distribution map shows specific location in the
study area where it is always cloudy all the year and the site corresponding soil
moisture content map came in agreement with cloud distribution. The overlay of
the two previously mentioned maps over the geological map of the study area shows
potential locations for better rainwater harvesting.
PMID- 25114970
TI - The p85 regulatory subunit of PI3K mediates cAMP-PKA and insulin biological
effects on MCF-7 cell growth and motility.
AB - Recent studies have shown that hyperinsulinemia may increase the cancer risk.
Moreover, many tumors demonstrate an increased activation of IR signaling
pathways. Phosphatidylinositol 3-kinase (PI3K) is necessary for insulin action.
In epithelial cells, which do not express GLUT4 and gluconeogenic enzymes,
insulin-mediated PI3K activation regulates cell survival, growth, and motility.
Although the involvement of the regulatory subunit of PI3K (p85alpha (PI3K)) in
insulin signal transduction has been extensively studied, the function of its N
terminus remains elusive. It has been identified as a serine (S83) in the
p85alpha (PI3K) that is phosphorylated by protein kinase A (PKA). To determine
the molecular mechanism linking PKA to insulin-mediated PI3K activation, we used
p85alpha (PI3K) mutated forms to prevent phosphorylation (p85A) or to mimic the
phosphorylated residue (p85D). We demonstrated that phosphorylation of p85alpha
(PI3K)S83 modulates the formation of the p85alpha (PI3K)/IRS-1 complex and its
subcellular localization influencing the kinetics of the insulin signaling both
on MAPK-ERK and AKT pathways. Furthermore, the p85alpha (PI3K)S83 phosphorylation
plays a central role in the control of insulin-mediated cell proliferation, cell
migration, and adhesion. This study highlights the p85alpha (PI3K)S83 role as a
key regulator of cell proliferation and motility induced by insulin in MCF-7
cells breast cancer model.
PMID- 25114972
TI - Service life assessment of historical building envelopes constructed using
different types of sandstone: a computational analysis based on experimental
input data.
AB - Service life assessment of three historical building envelopes constructed using
different types of sandstone is presented. At first, experimental measurements of
material parameters of sandstones are performed to provide the necessary input
data for a subsequent computational analysis. In the second step, the moisture
and temperature fields across the studied envelopes are calculated for a
representative period of time. The computations are performed using dynamic
climatic data as the boundary conditions on the exterior side of building
envelope. The climatic data for three characteristic localities are
experimentally determined by the Czech Hydrometeorological Institute and contain
hourly values of temperature, relative humidity, rainfalls, wind velocity and
direction, and sun radiation. Using the measured durability properties of the
analyzed sandstones and the calculated numbers of freeze/thaw cycles under
different climatic conditions, the service life of the investigated building
envelopes is assessed. The obtained results show that the climatic conditions can
play a very significant role in the service life assessment of historical
buildings, even in the conditions of such a small country as the Czech Republic.
In addition, the investigations reveal the importance of the material
characteristics of sandstones, in particular the hygric properties, on their
service life in a structure.
PMID- 25114975
TI - Security techniques for prevention of rank manipulation in social tagging
services including robotic domains.
AB - With smartphone distribution becoming common and robotic applications on the
rise, social tagging services for various applications including robotic domains
have advanced significantly. Though social tagging plays an important role when
users are finding the exact information through web search, reliability and
semantic relation between web contents and tags are not considered. Spams are
making ill use of this aspect and put irrelevant tags deliberately on contents
and induce users to advertise contents when they click items of search results.
Therefore, this study proposes a detection method for tag-ranking manipulation to
solve the problem of the existing methods which cannot guarantee the reliability
of tagging. Similarity is measured for ranking the grade of registered tag on the
contents, and weighted values of each tag are measured by means of synonym
relevance, frequency, and semantic distances between tags. Lastly, experimental
evaluation results are provided and its efficiency and accuracy are verified
through them.
PMID- 25114974
TI - Expression of a splice variant of CYP26B1 in betel quid-related oral cancer.
AB - Betel quid (BQ) is a psychostimulant, an addictive substance, and a group 1
carcinogen that exhibits the potential to induce adverse health effects.
Approximately, 600 million users chew a variety of BQ. Areca nut (AN) is a
necessary ingredient in BQ products. Arecoline is the primary alkaloid in the AN
and can be metabolized through the cytochrome P450 (CYP) superfamily by inducing
reactive oxygen species (ROS) production. Full-length CYP26B1 is related to the
development of oral pharyngeal cancers. We investigated whether a splice variant
of CYP26B1 is associated with the occurrence of ROS related oral and pharyngeal
cancer. Cytotoxicity assays were used to measure the effects of arecoline on cell
viability in a dose-dependent manner. In vitro and in vivo studies were conducted
to evaluate the expression of the CYP26B1 splice variant. The CYP26B1 splice
variant exhibited lower expression than did full-length CYP26B1 in the human
gingival fibroblast-1 and Ca9-22 cell models. Increased expression of the CYP26B1
splice variant was observed in human oral cancer tissue compared with adjacent
normal tissue, and increased expression was observed in patients at a late tumor
stage. Our results suggested that the CYP26B1 splice variant is associated with
the occurrence of BQ-related oral cancer.
PMID- 25114977
TI - An efficient image compressor for charge coupled devices camera.
AB - Recently, the discrete wavelet transforms- (DWT-) based compressor, such as
JPEG2000 and CCSDS-IDC, is widely seen as the state of the art compression scheme
for charge coupled devices (CCD) camera. However, CCD images project on the DWT
basis to produce a large number of large amplitude high-frequency coefficients
because these images have a large number of complex texture and contour
information, which are disadvantage for the later coding. In this paper, we
proposed a low-complexity posttransform coupled with compressing sensing (PT-CS)
compression approach for remote sensing image. First, the DWT is applied to the
remote sensing image. Then, a pair base posttransform is applied to the DWT
coefficients. The pair base are DCT base and Hadamard base, which can be used on
the high and low bit-rate, respectively. The best posttransform is selected by
the l p -norm-based approach. The posttransform is considered as the sparse
representation stage of CS. The posttransform coefficients are resampled by
sensing measurement matrix. Experimental results on on-board CCD camera images
show that the proposed approach significantly outperforms the CCSDS-IDC-based
coder, and its performance is comparable to that of the JPEG2000 at low bit rate
and it does not have the high excessive implementation complexity of JPEG2000.
PMID- 25114976
TI - 3D analysis of D-RaCe and self-adjusting file in removing filling materials from
curved root canals instrumented and filled with different techniques.
AB - The aim of this study was to compare the efficacy of D-RaCe files and a self
adjusting file (SAF) system in removing filling material from curved root canals
instrumented and filled with different techniques by using microcomputed
tomography (micro-CT). The mesial roots of 20 extracted mandibular first molars
were used. Root canals (mesiobuccal and mesiolingual) were instrumented with SAF
or Revo-S. The canals were then filled with gutta-percha and AH Plus sealer using
cold lateral compaction or thermoplasticized injectable techniques. The root
fillings were first removed with D-RaCe (Step 1), followed by Step 2, in which a
SAF system was used to remove the residual fillings in all groups. Micro-CT scans
were used to measure the volume of residual filling after root canal filling,
reinstrumentation with D-RaCe (Step 1), and reinstrumentation with SAF (Step 2).
Data were analyzed using Wilcoxon and Kruskal-Wallis tests. There were no
statistically significant differences between filling techniques in the canals
instrumented with SAF (P = 0.292) and Revo-S (P = 0.306). The amount of remaining
filling material was similar in all groups (P = 0.363); all of the
instrumentation techniques left filling residue inside the canals. However, the
additional use of SAF was more effective than using D-RaCe alone.
PMID- 25114978
TI - Density-based penalty parameter optimization on C-SVM.
AB - The support vector machine (SVM) is one of the most widely used approaches for
data classification and regression. SVM achieves the largest distance between the
positive and negative support vectors, which neglects the remote instances away
from the SVM interface. In order to avoid a position change of the SVM interface
as the result of an error system outlier, C-SVM was implemented to decrease the
influences of the system's outliers. Traditional C-SVM holds a uniform parameter
C for both positive and negative instances; however, according to the different
number proportions and the data distribution, positive and negative instances
should be set with different weights for the penalty parameter of the error
terms. Therefore, in this paper, we propose density-based penalty parameter
optimization of C-SVM. The experiential results indicated that our proposed
algorithm has outstanding performance with respect to both precision and recall.
PMID- 25114979
TI - The axioms independence of pseudo-weak-R0 algebras and filters.
AB - The most simplified axiom systems of pseudo-weak-R0 algebras and pseudo-R0
algebras are obtained, and the mutually independence of axioms is proved. We
introduce the notions of filters and normal filters in pseudo-weak-R0 algebras.
The structures and properties of the generated filters and generated normal
filters in pseudo-weak-R0 algebras are obtained. These can be seen as
noncommutative generalizations of the corresponding ones in weak-R0 algebras.
PMID- 25114980
TI - Identification of the causative disease of intermittent claudication through
walking motion analysis: feature analysis and differentiation.
AB - Intermittent claudication is a walking symptom. Patients with intermittent
claudication experience lower limb pain after walking for a short time. However,
rest relieves the pain and allows the patient to walk again. Unfortunately, this
symptom predominantly arises from not 1 but 2 different diseases: LSS (lumber
spinal canal stenosis) and PAD (peripheral arterial disease). Patients with LSS
can be subdivided by the affected vertebra into 2 main groups: L4 and L5. It is
clinically very important to determine whether patients with intermittent
claudication suffer from PAD, L4, or L5. This paper presents a novel SVM-
(support vector machine-) based methodology for such
discrimination/differentiation using minimally required data, simple walking
motion data in the sagittal plane. We constructed a simple walking measurement
system that is easy to set up and calibrate and suitable for use by
nonspecialists in small spaces. We analyzed the obtained gait patterns and
derived input parameters for SVM that are also visually detectable and medically
meaningful/consistent differentiation features. We present a differentiation
methodology utilizing an SVM classifier. Leave-one-out cross-validation of
differentiation/classification by this method yielded a total accuracy of 83%.
PMID- 25114981
TI - Models for 31-mode PVDF energy harvester for wearable applications.
AB - Currently, wearable electronics are increasingly widely used, leading to an
increasing need of portable power supply. As a clean and renewable power source,
piezoelectric energy harvester can transfer mechanical energy into electric
energy directly, and the energy harvester based on polyvinylidene difluoride
(PVDF) operating in 31-mode is appropriate to harvest energy from human motion.
This paper established a series of theoretical models to predict the performance
of 31-mode PVDF energy harvester. Among them, the energy storage one can predict
the collected energy accurately during the operation of the harvester. Based on
theoretical study and experiments investigation, two approaches to improve the
energy harvesting performance have been found. Furthermore, experiment results
demonstrate the high accuracies of the models, which are better than 95%.
PMID- 25114982
TI - Skin cancer by state and territory.
AB - There is a paucity of Australian state-based data on the incidence of non
melanoma skin cancer (NMSC). Basal cell carcinoma (BCC) and squamous cell
carcinoma (SCC) of the skin are not notifiable diseases and are not collected by
the state and territory cancer registries. In a 2002 survey, the Australian age
standardised incidence per 100,000 persons for NMSC was 1170 (BCC 884, SCC 387),
with a higher incidence in the northern latitudes.
PMID- 25114983
TI - The role of risk tools in diagnosing cancer in primary care.
AB - BACKGROUND: Diagnosing cancer on the basis of a patient's symptoms and risk
factors is a core role for general practice. Equally, as part of a cost-effective
health system, GPs should avoid over-investigation or referral of patients who
are very unlikely to have cancer. Diagnosing cancer in primary care is not
straightforward because many of the symptoms of cancer have more common benign
causes. OBJECTIVE: The aim of this article is to review the use of risk tools for
diagnosing cancer in primary care. DISCUSSION: Certain cancers, such as lung,
pancreas, ovary and myeloma, are particularly challenging to diagnose early.
National guidelines exist to support identification of patients who are more
likely to have an undiagnosed cancer but these list single symptoms as so-called
'red flags'. Validated risk tools, developed in general practice, exist that
predict cancer diagnosis on the basis of patterns of symptoms and risk factors.
These tools might prove useful in supporting cancer diagnosis in general practice
and also reducing investigation of patients at very low risk of cancer.
PMID- 25114984
TI - End-of-life care for patients with cancer.
AB - BACKGROUND: End-of-life care is a core role of general practice. Patients with
disseminated cancer have rapidly escalating needs at the end of life that are
usually predictable and, therefore, planning for future needs is possible. Care
planning and working with specialist palliative care colleagues improves patient
outcomes. OBJECTIVE: The aim of this article is to provide an overview of end-of
life care for patients with cancer, including evidence supporting the involvement
of general practitioners (GPs). DISCUSSION: Care planning is predicated on
understanding the patient's wishes about how care should be conducted and
ensuring the plan conforms to these wishes. Not all GPs are willing to undertake
palliative care, often because of a sense of inadequate knowledge, confidence and
support. The more palliative care is undertaken, however, the more confident
practitioners feel. Therefore, starting to treat end-of-life patients early in a
GP's career is important, and making use of the considerable resources available
will assist in building knowledge and confidence. Systematically caring for
carers might be a way of introducing GPs to the care of patients with cancer at
the end of life.
PMID- 25114985
TI - Cancer survivorship--the role of the GP.
AB - BACKGROUND: Improvements in cancer detection, treatment and an ageing population
mean that there are increasing numbers of people living with and beyond cancer.
Current hospital-centred models of cancer follow-up have tended to focus on
detection of cancer recurrence, which may result in significant unmet needs,
particularly psychosocial needs. OBJECTIVE: This paper discusses the evidence
from previous studies of primary care involvement in cancer survivorship and key
areas to consider in the follow-up care for common cancers. DISCUSSION: General
practice has an important role in the holistic care of cancer survivors and could
take on an expanded role in cancer follow-up.
PMID- 25114986
TI - Advance care planning.
AB - BACKGROUND: Good Medical Practice: A Code of Conduct for Doctors in Australia
states that in caring for patients towards the end of their life, good medical
practice involves facilitating advance care planning. OBJECTIVE: This article
discusses the role of advance care planning in end-of-life care, with an emphasis
on the ethical and legal framework for advance care directives. DISCUSSION: There
has been an increased focus on advanced care planning and advance care directives
in Australia, partly driven by the ageing population and technological advances,
as well as the principle of patient-centred care. General practitioners have an
important role in initiating and facilitating advance care planning.
PMID- 25114987
TI - Back pain in a cancer patient: a case study.
PMID- 25114988
TI - 'Help us, she's fading away': How to manage the patient with anorexia nervosa.
AB - BACKGROUND: Although integral to the early detection and treatment of anorexia
nervosa, there is a paucity of clear guidance available for general practitioners
(GPs). This paper attempts to bridge the gap between the specialist and
generalist literature to assist the busy GP feel confident in identifying and
managing these patients. OBJECTIVE: On reading this article it is anticipated the
GP will feel well equipped to screen for and provide ongoing treatment to
patients who pre-sent with eating disorders, particularly anorexia nervosa. This
paper provides guidance for the identification and ongoing management of patients
with anorexia nervosa, and supporting their carers. DISCUSSION: People affected
by eating disorders, particularly anorexia nervosa, may deny having a problem,
minimise their symptoms and resist treatment yet engage partially with their GP
throughout the course of their illness. There are well-validated, quick screening
tools that the non-specialist can use to identify patients at high risk of having
an eating disorder.
PMID- 25114989
TI - GP pain management: what are the 'Ps' and 'As' of pain management?
AB - BACKGROUND: Pain is one common reason for clinical encounters in primary care.
The complex nature of chronic pain syndromes can make assessment and management
daunting at times. OBJECTIVE: This article presents an easy scheme to help
general practitioners efficiently assess, manage and review/follow up patients
with chronic pain. DISCUSSION: The mnemonic presented for assessment is the '4Ps'
(pain, other pathology/past medical history, performance/function and
psychological/psychiatric status). For management, we can also use '4Ps'
(physical, psychological, pharmacological and procedural) and for review there
are the '6As' (activities, analgesia, adverse effects, aberrance behaviours,
affects and adequate documentation).
PMID- 25114990
TI - Exercise in pregnancy.
AB - BACKGROUND: Exercise is an inconsistently managed area in the health of expectant
mothers. It is an area where family doctors have an opportunity to be well
informed and willing to give advice. OBJECTIVE: To provide simple advice on safe
exercise practice in pregnancy. DISCUSSION: Exercise in pregnancy has multiple
benefits for the mother, including reduced risk of mental health problems,
diabetes and hypertension, and faster recovery after delivery. There are no
proven risks to the fetus if practiced safely. Understanding the physiological
changes of pregnancy and the possible complications of high-intensity or contact
sport is important but in general, moderate levels of exercise 3-4 times per week
is safe for both mother and baby in low-risk pregnancies.
PMID- 25114991
TI - Periorbital oedema after dental extraction: a case study.
PMID- 25114992
TI - A heavy burden: remaining vigilant with herbal remedies.
PMID- 25114993
TI - Ulcerated upper lip tumour: diagnostic procedure.
AB - A Mediterranean Spanish woman, aged 56 years and in good health, presented with a
nodule above her upper lip, which had rapidly evolved to central ulceration with
crusting. As part of the work-up, samples were taken for microbiological and
histopathological investigation. At the follow-up appointment the lesion had
almost disappeared and a small fibrotic area of scarring remained. The diagnostic
procedure to distinguish between localised cutaneous leishmaniasis and
keratoacanthoma, both characterised by rapidly growing nodules on the face, is
presented in this case-based article.
PMID- 25114994
TI - Self-reported access to and quality of healthcare for diabetes: do the severely
obese experience equal access?
AB - BACKGROUND: Given reported pejorative views that health professionals have about
patients who are severely obese, we examined the self-reported views of the
quality and availability of diabetes care from the perspective of adults with
type 2 diabetes (T2DM), stratified by body mass index (BMI). METHODS: 1795
respondents to the Diabetes MILES - Australia national survey had T2DM. Of these,
530 (30%) were severely obese (BMI >=35 kg/m2) and these participants were
matched with 530 controls (BMI <35 kg/m2). Data regarding participants' self
reported interactions with health practitioners and services were compared.
RESULTS: Over 70% of participants reported that their general practitioner was
the professional they relied on most for diabetes care. There were no between
group differences in patient-reported availability of health services, quality of
interaction with health practitioners, resources and support for self-management,
or access to almost all diabetes services. DISCUSSION: Participants who were
severely obese did not generally report greater difficulty in accessing diabetes
care.
PMID- 25114995
TI - Predicting recovery from whiplash injury in the primary care setting.
AB - BACKGROUND: The effect of expectation of recovery on the recovery rate of
whiplash patients in the primary care setting is not known. METHODS: Whiplash
patients were assessed in a primary care setting within 1 week of their collision
for their expectations of recovery and were re-examined 3 months later for
recovery. RESULTS: Initial expectations of recovery predicted recovery. According
to adjusted odds ratios, subjects who expected 'to get better slowly' had a
recovery rate that was nearly 1.9 times that of subjects with poor recovery
expectations. Subjects who expected 'to get better soon' had a recovery rate that
was 2.6 times greater than either of those with poor recovery expectations.
DISCUSSION: In the primary care setting, asking patients with whiplash about
their expectations of recovery is a useful predictor of their outcome.
PMID- 25114996
TI - Outpatient alcohol withdrawal management for Aboriginal and Torres Strait
Islander peoples.
AB - BACKGROUND: There is concern from within Aboriginal and Torres Strait Islander
communities about the lack of access to alcohol withdrawal management ('detox')
services. Outpatient detox is described within national Australian guidelines as
a safe option for selected drinkers. However, uncertainly exists as to how suited
Aboriginal and Torres Strait Islander peoples are to this approach. ? METHODS:
Consultations were conducted with stakeholders of four health services providing
outpatient detox for Aboriginal and Torres Strait Islander peoples in NSW.
Thematic analysis was performed to determine elements perceived as important for
success. RESULTS: Key themes that emerged were individual engagement,
flexibility, assessment of suitability, Aboriginal staff and community
engagement, practical support, counselling, staff education and support, coping
with relapse and contingency planning. ? DISCUSSION: There is a need to improve
access to alcohol detox services for Aboriginal and Torres Strait Islander
peoples. The outpatient setting seems to be a feasible and safe environment to
provide this kind of service for selected drinkers.
PMID- 25114997
TI - Misoprostol for post-partum haemorrhage in the Australian bush.
AB - Obstetric haemorrhage, particularly post-partum haemorrhage has been noted to be
the third most common direct cause of maternal deaths. According to the
Australian Institute of Health and Welfare (AIHW), bleeding contributed up to 14%
of maternal deaths caused by obstetric complications between the years 2003 and
2005.
PMID- 25114998
TI - The importance of LPNs.
PMID- 25114999
TI - Author's response.
PMID- 25115001
TI - WHO and partners launch Ebola response plan.
PMID- 25115000
TI - Reply to Lopez et al.: Consumption-based accounting helps mitigate global air
pollution.
PMID- 25115002
TI - Multiple crises overwhelm emergency food relief agencies.
PMID- 25115003
TI - Funding: Wellcome Trust selects sustainable health projects.
PMID- 25115004
TI - Jeannie Isabelle Rosoff.
PMID- 25115006
TI - Biotechnology of food additives. Preface.
PMID- 25115005
TI - Studies of local structural distortions in strained ultrathin BaTiO3 films using
scanning transmission electron microscopy.
AB - Ultrathin ferroelectric heterostructures (SrTiO3/BaTiO3/BaRuO3/SrRuO3) were
studied by scanning transmission electron microscopy (STEM) in terms of
structural distortions and atomic displacements. The TiO2-termination at the top
interface of the BaTiO3 layer was changed into a BaO-termination by adding an
additional BaRuO3 layer. High-angle annular dark-field (HAADF) imaging by
aberration-corrected STEM revealed that an artificially introduced BaO
termination can be achieved by this interface engineering. By using fast
sequential imaging and frame-by-frame drift correction, the effect of the
specimen drift was significantly reduced and the signal-to-noise ratio of the
HAADF images was improved. Thus, a quantitative analysis of the HAADF images was
feasible, and an in-plane and out-of-plane lattice spacing of the BaTiO3 layer of
3.90 and 4.22 A were determined. A 25 pm shift of the Ti columns from the center
of the unit cell of BaTiO3 along the c-axis was observed. By spatially resolved
electron energy-loss spectroscopy studies, a reduction of the crystal field
splitting (CFS, DeltaL3=1.93 eV) and an asymmetric broadening of the eg peak were
observed in the BaTiO3 film. These results verify the presence of a ferroelectric
polarization in the ultrathin BaTiO3 film.
PMID- 25115007
TI - Hellbender genome sequences shed light on genomic expansion at the base of crown
salamanders.
AB - Among animals, genome sizes range from 20 Mb to 130 Gb, with 380-fold variation
across vertebrates. Most of the largest vertebrate genomes are found in
salamanders, an amphibian clade of 660 species. Thus, salamanders are an
important system for studying causes and consequences of genomic gigantism.
Previously, we showed that plethodontid salamander genomes accumulate higher
levels of long terminal repeat (LTR) retrotransposons than do other vertebrates,
although the evolutionary origins of such sequences remained unexplored. We also
showed that some salamanders in the family Plethodontidae have relatively slow
rates of DNA loss through small insertions and deletions. Here, we present new
data from Cryptobranchus alleganiensis, the hellbender. Cryptobranchus and
Plethodontidae span the basal phylogenetic split within salamanders; thus,
analyses incorporating these taxa can shed light on the genome of the ancestral
crown salamander lineage, which underwent expansion. We show that high levels of
LTR retrotransposons likely characterize all crown salamanders, suggesting that
disproportionate expansion of this transposable element (TE) class contributed to
genomic expansion. Phylogenetic and age distribution analyses of salamander LTR
retrotransposons indicate that salamanders' high TE levels reflect persistence
and diversification of ancestral TEs rather than horizontal transfer events.
Finally, we show that relatively slow DNA loss rates through small indels likely
characterize all crown salamanders, suggesting that a decreased DNA loss rate
contributed to genomic expansion at the clade's base. Our identification of
shared genomic features across phylogenetically distant salamanders is a first
step toward identifying the evolutionary processes underlying accumulation and
persistence of high levels of repetitive sequence in salamander genomes.
PMID- 25115008
TI - Frequent changes in expression profile and accelerated sequence evolution of
duplicated imprinted genes in arabidopsis.
AB - Eukaryotic genomes have large numbers of duplicated genes that can evolve new
functions or expression patterns by changes in coding and regulatory sequences,
referred to as neofunctionalization. In flowering plants, some duplicated genes
are imprinted in the endosperm, where only one allele is expressed depending on
its parental origin. We found that 125 imprinted genes in Arabidopsis arose from
gene duplication events during the evolution of the Brassicales. Analyses of 46
gene pairs duplicated by an ancient whole-genome duplication (alpha WGD)
indicated that many imprinted genes show an accelerated rate of amino acid
changes compared with their paralogs. Analyses of microarray expression data from
63 organ types and developmental stages indicated that many imprinted genes have
expression patterns restricted to flowers and/or seeds in contrast to their
broadly expressed paralogs. Assays of expression in orthologs from outgroup
species revealed that some imprinted genes have acquired an organ-specific
expression pattern restricted to flowers and/or seeds. The changes in expression
pattern and the accelerated sequence evolution in the imprinted genes suggest
that some of them may have undergone neofunctionalization. The imprinted genes
MPC, HOMEODOMAIN GLABROUS6 (HDG6), and HDG3 are particularly interesting cases
that have different functions from their paralogs. This study indicates that a
large number of imprinted genes in Arabidopsis are evolutionarily recent
duplicates and that many of them show changes in expression profiles and
accelerated sequence evolution. Acquisition of imprinting is a mode of duplicate
gene divergence in plants that is more common than previously thought.
PMID- 25115009
TI - The effects of microsatellite selection on linked sequence diversity.
AB - The genome-wide scan for selection is an important method for identifying loci
involved in adaptive evolution. However, theory that underlies standard scans for
selection assumes a simple mutation model. In particular, recurrent mutation of
the selective target is not considered. Although this assumption is reasonable
for single-nucleotide variants (SNVs), a microsatellite targeted by selection
will reliably violate this assumption due to high mutation rate. Moreover, the
mutation rate of microsatellites is generally high enough to ensure that
recurrent mutation is pervasive rather than occasional. It is therefore unclear
if positive selection targeting microsatellites can be detected using standard
scanning statistics. Examples of functional variation at microsatellites
underscore the significance of understanding the genomic effects of
microsatellite selection. Here, we investigate the joint effects of selection and
complex mutation on linked sequence diversity, comparing simulations of
microsatellite selection and SNV-based selective sweeps. We find that selection
on microsatellites is generally difficult to detect using popular summaries of
the site frequency spectrum, and, under certain conditions, using popular methods
such as the integrated haplotype statistic and SweepFinder. However, comparisons
of the number of haplotypes (K) and segregating sites (S) often provide
considerable power to detect selection on microsatellites. We apply this
knowledge to a scan of autosomes in the human CEU population (CEPH population
sampled from Utah). In addition to the most commonly reported targets of
selection in European populations, we identify numerous novel genomic regions
that bear highly anomalous haplotype configurations. Using one of these regions
intron 1 of MAGI2-as an example, we show that the anomalous configuration is
coincident with a perfect CA repeat of length 22. We conclude that standard
genome-wide scans will commonly fail to detect mutationally complex targets of
selection but that comparisons of K and S will, in many cases, facilitate their
identification.
PMID- 25115010
TI - Evolutionary dynamics of the mitochondrial genome in the evaniomorpha
(hymenoptera)-a group with an intermediate rate of gene rearrangement.
AB - We determined the complete mitochondrial (mt) genomes of three evaniomorph
species, Ceraphron sp. (Ceraphronoidea), Gasteruption sp. (Evanioidea), and
Orthogonalys pulchella (Trigonalyoidea) as well as the nearly complete mt genome
from another evaniomorph species, Megalyra sp. (Megalyroidea). Each of them
possesses dramatic gene rearrangements, including protein-coding or rRNA genes.
Gene inversions were identified in all of these mt genomes; for example, the two
rRNA genes have inverted and moved into the nad2-cox1 junction in the Megalyra
sp. mt genome. In addition, we found two copies of a 10-bp complementary repeat
at the beginning of rrnS and at the end of trnL(2) in the Gasteruption sp. mt
genome, consistent with recombination as the possible mechanism for gene
inversion and long-range movement. Although each of the genomes contains a number
of repeats of varying size, there was no consistent association of the size or
number of repeats with the extent or type of gene rearrangement. The breakpoint
distance analysis showed the Evaniomorpha has an intermediate rate of gene
rearrangement. Sequence-based phylogenetic analyses of 13 protein-coding and 2
rRNA genes in 22 hymenopteran taxa recovered a paraphyletic Evaniomorpha with the
Aculeata nested within it. Within the Evaniomorpha, our analyses confirmed the
Trigonalyoidea + Megalyroidea as the sister group to the Aculeata and recovered a
novel clade, Ceraphronoidea + Evanioidea. In contrast to previous hymenopteran
phylogenetic studies, the internal relationships of the Evaniomorpha were highly
supported and robust to the variation of alignment approach and phylogenetic
inference approach.
PMID- 25115011
TI - Small but powerful, the primary endosymbiont of moss bugs, Candidatus Evansia
muelleri, holds a reduced genome with large biosynthetic capabilities.
AB - Moss bugs (Coleorrhyncha: Peloridiidae) are members of the order Hemiptera, and
like many hemipterans, they have symbiotic associations with intracellular
bacteria to fulfill nutritional requirements resulting from their unbalanced
diet. The primary endosymbiont of the moss bugs, Candidatus Evansia muelleri, is
phylogenetically related to Candidatus Carsonella ruddii and Candidatus Portiera
aleyrodidarum, primary endosymbionts of psyllids and whiteflies, respectively. In
this work, we report the genome of Candidatus Evansia muelleri Xc1 from Xenophyes
cascus, which is the only obligate endosymbiont present in the association. This
endosymbiont possesses an extremely reduced genome similar to Carsonella and
Portiera. It has crossed the borderline to be considered as an autonomous cell,
requiring the support of the insect host for some housekeeping cell functions.
Interestingly, in spite of its small genome size, Evansia maintains enriched
amino acid (complete or partial pathways for ten essential and six nonessential
amino acids) and sulfur metabolisms, probably related to the poor diet of the
insect, based on bryophytes, which contains very low levels of nitrogenous and
sulfur compounds. Several facts, including the congruence of host (moss bugs,
whiteflies, and psyllids) and endosymbiont phylogenies and the retention of the
same ribosomal RNA operon during genome reduction in Evansia, Portiera, and
Carsonella, suggest the existence of an ancient endosymbiotic Halomonadaceae
clade associated with Hemiptera. Three possible scenarios for the origin of these
three primary endosymbiont genera are proposed and discussed.
PMID- 25115013
TI - Author response.
PMID- 25115014
TI - Retraction. "Haemodynamic derangement in human immunodeficiency virus-infected
patients with hepatitis C virus-related cirrhosis: the role of bacterial
translocation".
PMID- 25115012
TI - The molecular evolution of the Qo motif.
AB - Quinol oxidation in the catalytic quinol oxidation site (Q(o) site) of cytochrome
(cyt) bc(1) complexes is the key step of the Q cycle mechanism, which laid the
ground for Mitchell's chemiosmotic theory of energy conversion. Bifurcated
electron transfer upon quinol oxidation enables proton uptake and release on
opposite membrane sides, thus generating a proton gradient that fuels ATP
synthesis in cellular respiration and photosynthesis. The Q(o) site architecture
formed by cyt b and Rieske iron-sulfur protein (ISP) impedes harmful bypass
reactions. Catalytic importance is assigned to four residues of cyt b formerly
described as PEWY motif in the context of mitochondrial complexes, which we now
denominate Q(o) motif as comprehensive evolutionary sequence analysis of cyt b
shows substantial natural variance of the motif with phylogenetically specific
patterns. In particular, the Q(o) motif is identified as PEWY in mitochondria,
alpha- and epsilon-Proteobacteria, Aquificae, Chlorobi, Cyanobacteria, and
chloroplasts. PDWY is present in Gram-positive bacteria, Deinococcus-Thermus and
haloarchaea, and PVWY in beta- and gamma-Proteobacteria. PPWF only exists in
Archaea. Distinct patterns for acidophilic organisms indicate environment
specific adaptations. Importantly, the presence of PDWY and PEWY is correlated
with the redox potential of Rieske ISP and quinone species. We propose that
during evolution from low to high potential electron-transfer systems in the
emerging oxygenic atmosphere, cyt bc(1) complexes with PEWY as Q(o) motif
prevailed to efficiently use high potential ubiquinone as substrate, whereas cyt
b with PDWY operate best with low potential Rieske ISP and menaquinone, with the
latter being the likely composition of the ancestral cyt bc(1) complex.
PMID- 25115015
TI - Chronic ulceration of tongue. Histoplasmosis.
PMID- 25115016
TI - Newborn skin care guidelines, third edition.
PMID- 25115018
TI - Mentoring: have you thought of a formal program?
PMID- 25115019
TI - PED virus reinfecting U.S. herds. Virus estimated to have killed 7 million-plus
pigs.
PMID- 25115020
TI - Agreement will reduce access to some rodenticides.
PMID- 25115021
TI - Help line getting more calls about bromethalin.
PMID- 25115022
TI - Editorial.
PMID- 25115023
TI - SENTIERI Project: Introduction.
PMID- 25115024
TI - [Psychopathological mechanisms of childhood trauma].
PMID- 25115025
TI - [What is the present appropriate treatment for renal denervation hypertension?].
PMID- 25115026
TI - [Heat and criticism of mothers and behavioral problems in children with ADHD].
PMID- 25115027
TI - Findings of research misconduct.
PMID- 25115028
TI - Findings of research misconduct.
PMID- 25115030
TI - Findings of Research Misconduct.
PMID- 25115029
TI - Findings of research misconduct.
PMID- 25115031
TI - Long-term and trans-generational effects of neonatal experience on sheep
behaviour.
AB - Early life experiences can have profound long-term, and sometimes
transgenerational, effects on individual phenotypes. However, there is a relative
paucity of knowledge about effects on pain sensitivity, even though these may
impact on an individual's health and welfare, particularly in farm animals
exposed to painful husbandry procedures. Here, we tested in sheep whether
neonatal painful and non-painful challenges can alter pain sensitivity in adult
life, and also in the next generation. Ewes exposed to tail-docking or a
simulated mild infection (lipopolysaccharide (LPS)) on days 3-4 of life showed
higher levels of pain-related behaviour when giving birth as adults compared with
control animals. LPS-treated ewes also gave birth to lambs who showed decreased
pain sensitivity in standardized tests during days 2-3 of life. Our results
demonstrate long-term and trans-generational effects of neonatal experience on
pain responses in a commercially important species and suggest that variations in
early life management can have important implications for animal health and
welfare.
PMID- 25115032
TI - Ectomycorrhizal fungi and past high CO2 atmospheres enhance mineral weathering
through increased below-ground carbon-energy fluxes.
AB - Field studies indicate an intensification of mineral weathering with advancement
from arbuscular mycorrhizal (AM) to later-evolving ectomycorrhizal (EM) fungal
partners of gymnosperm and angiosperm trees. We test the hypothesis that this
intensification is driven by increasing photosynthate carbon allocation to
mycorrhizal mycelial networks using 14CO2-tracer experiments with representative
tree-fungus mycorrhizal partnerships. Trees were grown in either a simulated past
CO2 atmosphere (1500 ppm)-under which EM fungi evolved-or near-current CO2 (450
ppm). We report a direct linkage between photosynthate-energy fluxes from trees
to EM and AM mycorrhizal mycelium and rates of calcium silicate weathering.
Calcium dissolution rates halved for both AM and EM trees as CO2 fell from 1500
to 450 ppm, but silicate weathering by AM trees at high CO2 approached rates for
EM trees at near-current CO2. Our findings provide mechanistic insights into the
involvement of EM-associating forest trees in strengthening biological feedbacks
on the geochemical carbon cycle that regulate atmospheric CO2 over millions of
years.
PMID- 25115033
TI - Rodents of the Caribbean: origin and diversification of hutias unravelled by next
generation museomics.
AB - The Capromyidae (hutias) are endemic rodents of the Caribbean and represent a
model of dispersal for non-flying mammals in the Greater Antilles. This family
has experienced severe extinctions during the Holocene and its phylogenetic
affinities with respect to other caviomorph relatives are still debated as
morphological and molecular data disagree. We used target enrichment and next
generation sequencing of mitochondrial and nuclear genes to infer the
phylogenetic relationships of hutias, estimate their divergence ages, and
understand their mode of dispersal in the Greater Antilles.We found that
Capromyidae are nested within Echimyidae (spiny rats) and should be considered a
subfamily thereof. We estimated that the split between hutias and Atlantic Forest
spiny rats occurred 16.5 (14.8-18.2) million years ago (Ma), which is more recent
than the GAARlandia land bridge hypothesis (34-35 Ma). This would suggest that
during the Early Miocene, an echimyid-like ancestor colonized the Greater
Antilles from an eastern South American source population via rafting. The basal
divergence of the Hispaniolan Plagiodontia provides further support for a
vicariant separation between Hispaniolan and western islands (Bahamas, Cuba,
Jamaica) hutias. Recent divergences among these western hutias suggest Plio
Pleistocene dispersal waves associated with glacial cycles.
PMID- 25115034
TI - Implementing the Affordable Care Act: state action on quality improvement in
state-based marketplaces.
AB - Under the Affordable Care Act, the health insurance marketplaces can encourage
improvements in health care quality by: allowing consumers to compare plans based
on quality and value, setting common quality improvement requirements for
qualified health plans, and collecting quality and cost data to inform
improvements. This issue brief reviews actions taken by state-based marketplaces
to improve health care quality in three areas: 1) using selective contracting to
drive quality and delivery system reforms; 2) informing consumers about plan
quality; and 3) collecting data to inform quality improvement. Thirteen state
based marketplaces took action to promote quality improvement and delivery system
reforms through their marketplaces in 2014. Although technical and operational
challenges remain, marketplaces have the potential to drive systemwide changes in
health care delivery.
PMID- 25115035
TI - Caring for high-need, high-cost patients: what makes for a successful care
management program?
AB - Provider groups taking on risk for the overall costs of care in accountable care
organizations are developing care management programs to improve care and thereby
control costs. Many such programs target "high-need, high-cost" patients: those
with multiple or complex conditions, often combined with behavioral health
problems or socioeconomic challenges. In this study we compared the operational
approaches of 18 successful complex care management programs in order to offer
guidance to providers, payers, and policymakers on best practices for complex
care management. We found that effective programs customize their approach to
their local contexts and caseloads; use a combination of qualitative and
quantitative methods to identify patients; consider care coordination one of
their key roles; focus on building trusting relationships with patients as well
as their primary care providers; match team composition and interventions to
patient needs; offer specialized training for team members; and use technology to
bolster their efforts.
PMID- 25115036
TI - A review of avian probiotics.
AB - Probiotics have been used in poultry for decades and have become common in the
pet bird industry. Desirable characteristics of probiotic organisms are that they
are nonpathogenic, have the ability to adhere to intestinal epithelial cells,
have the ability to colonize and reproduce in the host, have the ability to be
host-specific, survive transit through the gastrointestinal tract and exposure to
stomach acid and bile, produce metabolites that inhibit or kill pathogenic
bacteria, modulate gastrointestinal immune responses, and survive processing and
storage. Purported benefits in birds are disease prevention and promotion of
growth. Recommendations for use in avian species are for periodic use to
replenish normal flora, use after antibiotic therapy to reestablish normal flora,
and use during periods of stress to counter effects of immunosuppression.
PMID- 25115037
TI - Pharmacokinetics of single oral dose of pimobendan in Hispaniolan Amazon parrots
(Amazona ventralis).
AB - Pimobendan is a phosphodiesterase (PDE) inhibitor and calcium sensitizer with
inotropic, lusitropic, and rasodilator properties used in the treatment of
congestive heart failure. The mechanism of action is by inhibition of PDE III and
V and by increasing intracellular calcium sensitivity in the cardiac myocardium.
Pharmacokinetic and pharmacodynamic studies have been published in humans, dogs,
and cats, but there are no studies in avian species. Pimobendan has been used in
birds at the empirical dosage of 0.25 mg/kg q12h. To determine the
pharmacokinetic parameters of pimobendan in Hispaniolan Amazon parrots (Amazona
ventralis), 3 pilot studies with 2 birds, each receiving 1, 3, and 10 mg/kg PO,
provided the basis for the pivotal trials with 6 birds, each receiving 10 mg/kg
PO using 2 different suspensions. Blood samples were obtained at 0, 0.5, 1, 1.5,
2, 3, 4, 8, 12, and 18 hours after drug administration. Plasma concentrations
were determined by liquid chromatography-tandem mass spectrometry (HPLC/MS) by
use of electrospray ionization. Because of the erratic and low concentrations of
pimobendan, pharmacokinetic parameters were calculated using naive averaged
analysis. Plasma concentrations after commercial pimobendan tablet suspension at
10 mg/kg reached a Cmax of 8.26 ng/mL at 3 hours with a terminal half-life of 2.1
hours, while concentrations after the bulk chemical suspension reached a Cmax of
1.28 ng/mL at 12 hours and had a terminal half-life of 2.3 hours. Further studies
evaluating the effect of oral pimobendan in parrots are needed.
PMID- 25115038
TI - Inhibition of the reproductive system by deslorelin in male and female pigeons
(Columba livia).
AB - Veterinary practitioners frequently encounter disorders of the reproductive
system in avian patients. Management of these disorders relies on manipulating
reproduction by modifying the environment, diet, and social interactions, and by
the use of pharmacologic agents and surgery, with varying levels of success and
side effects. An alternative is to use the gonadotropin-releasing hormone (GnRH)
agonist deslorelin to suppress the pituitary-gonadal axis. To determine the
efficacy of deslorelin in domestic pigeons (Columba livia), male (n = 10) and
female (n = 10) birds each were implanted intramuscularly with a single long
acting implant containing 4.7 mg deslorelin. Untreated males (n = 11) and females
(n = 10) were used as controls. The baseline serum concentration of luteinizing
hormone (LH) was assayed at 7, 28, 56, and 84 days after treatment, and egg
production was recorded weekly. In females, deslorelin administration
significantly reduced serum LH concentrations compared to pretreatment levels at
7, 28, 56, and 84 days (P < .05). In males, deslorelin significantly reduced LH
concentrations at 7, 28, and 56 days (P < .05). Female birds treated with
deslorelin laid significantly fewer eggs over the course of the study (mean =
1.46, SEM = 0.84) compared with controls (mean = 5.54, SEM = 0.88). Deslorelin
treatment had no discernible effect on body weight. Deslorelin is effective for
controlling egg laying in female pigeons for at least 49 days, but further
research is required to determine the effects on male fertility and the duration
of action in both sexes.
PMID- 25115040
TI - Reference intervals, longitudinal analyses, and index of individuality of
commonly measured laboratory variables in captive bald eagles (Haliaeetus
leucocephalus).
AB - The objectives of this study were to determine reference intervals, perform
longitudinal analyses, and determine the index of individuality (IoI) of 8
hematologic, and 13 biochemical and electrophoretic variables for a group of
captive bald eagles (Haliaeetus leucocephalus). Reference intervals were
determined from blood samples collected during annual wellness examinations for
41 eagles (23 male and 18 female) with ages ranging between 6 and 43 years (18.7
+/- 7.4, mean +/- SD) at the time of sample collection. Longitudinal analyses and
IoI were determined for measured hematologic, biochemical, and protein
electrophoretic variables, both individually and as a group, for a subset of 16
eagles (10 male and 6 female) during a 12-year period. This smaller group of
eagles ranged in age between 2 and 20 years at the start of the study period, and
between 14 and 32 years (21.9 +/- 5.0, mean +/- SD) at the end of the study
period. Significant increases with age within the group of 16 eagles were
observed only for red blood cells, percent heterophils, total protein, and beta
globulin protein fraction, while albumin:globulin decreased significantly with
age. A low IoI (> or = 1.4) was determined for all hematologic and biochemical
variables except gamma globulins, which had high IoI (< or = 0.6) for 3
individuals within the subset of 16.
PMID- 25115039
TI - Nonmedical factors associated with feather picking in pet psittacine birds.
AB - A nested case-control study was performed to determine nonmedical risk factors
associated with feather picking in psittacine birds. Forty-two case birds,
reported by their owners to pick their feathers, and 126 unaffected birds were
compared. The odds of feather picking were higher in 2 species categories,
African grey parrots (Psitticus erithacus, adjusted odds ratio [ORadj = 8.4, P <
.001) and cockatoos (Cacatua species, ORadj = 12.7, P < .001). The odds of
feather picking also were higher for birds that were out of their cages more than
8 hours per day (ORadj = 7.4, P < .001) and for birds that had been taken in by
the owner as a "rescue" (ORadj = 4.7, P < .01). The odds of feather picking
decreased by almost 90% (ORadj = 0.1, P < .005) for birds that interacted with
people at least 4 hours a day. These findings identify characteristics that
practitioners may want to include when asking bird owners about behavioral
history and may be useful in focusing future research regarding this behavior.
PMID- 25115041
TI - American kestrel (Falco spaverius) fledgling with severe bilateral periorbital
swelling and infection with Mycoplasma buteonis, Avibacterium (Pasteurella)
gallinarum, and Staphylococcus pasteuri.
AB - Abstract: A female American kestrel (Falco spaverius) fledgling was found on the
ground with a suspected trauma to the right eye and open-mouth breathing. During
the first 2 days of hospitalization, the bird developed severe bilateral
periorbital cellulitis, blepharoedema, and sinusitis. The periocular tissues of
the right globe were devitalized and communicated with a fistula at the
commissure of the right side of the beak. The blepharoedema of the left eye was
aspirated and yielded a dark colored malodorous fluid, which was submitted for
aerobic bacterial and Mycoplasma cultures. Results showed a mixed infection with
Mycoplasma buteonis, Avibacterium gallinarum, and Staphylococcus pasteuri, all of
which are not commonly isolated from birds of prey. With antimicrobial therapy,
supportive care, and surgical debridement of the right periocular necrotic
tissues and adhesed phthisical globe, the kestrel recovered from this severe
mixed upper respiratory infection.
PMID- 25115042
TI - Central vestibular disease in a blue and gold macaw (Ara ararauna) with cerebral
infarction and hemorrhage.
AB - A 24-year-old female blue and gold macaw (Ara ararauna) was presented for an
acute onset of left head tilt. On examination, the macaw was dehydrated and had a
120-degree left head tilt, decreased proprioception of the left pelvic limb, and
intermittent vertical nystagmus. Results of hematologic testing and biochemical
analysis revealed severe leukocytosis with lymphopenia and heterophilia and a
high uric acid concentration. Radiographs showed bilateral intertarsal joint
osteoarthritis and a healed ulnar fracture. Magnetic resonance imaging of the
brain revealed focal T2 and fluid-attenuated inversion recovery hyperintense
lesions in the right cerebral hemisphere and in the midbrain. The midbrain lesion
showed susceptibility artifact on the T2* sequence, suggesting hemorrhage. In the
T2* sequence, iron accumulation (as seen with hemorrhage) distorts the magnetic
signal, resulting in the production of a susceptibility artifact, which can then
be visualized as a region of hypointensity. The bird was hospitalized but died
despite intensive care. Necropsy revealed multiple cerebral vascular lesions
including an acute cerebral infarct, a ruptured midbrain aneurysm, and multifocal
systemic atherosclerosis. To our knowledge, this is the first report of a
cerebral aneurysm in a bird. This report correlates the clinical presentation,
imaging, and histopathologic findings in a macaw with central vestibular disease
and demonstrates how advanced imaging techniques can identify hemorrhagic lesions
through the T2* sequence.
PMID- 25115044
TI - The "original" AAV: the founding of the Association of Avian Veterinarians.
PMID- 25115043
TI - Nasal adenocarcinoma and secondary chronic sinusitis in a hyacinth macaw
(Anodorhynchus hyacinthinus).
AB - An adult male hyacinth macaw (Anodorhynchus hyacinthinus) that presented for
acute onset nasal discharge and dyspnea had purulent discharge from the right
naris and serosanguineous discharge from the left naris on physical examination.
Results of a complete blood count revealed severe leukocytosis with a mature
heterophilia. Computed tomography scans showed a large amount of soft-tissue
attenuating material within the infraorbital sinus and associated diverticula.
Aerobic culture results of the nasal discharge showed a mixed population of
Staphylococcus intermedius and Pasteurella species, including Pasteurella
pneumotropica; all isolated bacteria were susceptible to enrofloxacin. Clinical
signs did not resolve over the course of 9 weeks of antibiotic treatment. The
macaw died after cardiopulmonary arrest while hospitalized. At necropsy, a 2 x 2
x 3-cm firm, tan, friable, space-occupying mass surrounded by a thick exudate was
present in the left preorbital diverticulum of the infraorbital sinus. The
cranioventral one-third of the trachea contained a 4 x 0.5-cm white-yellow
plaque. On histologic examination, the sinus mass was diagnosed as a nasal
adenocarcinoma, and the tracheal plaque was caused by fungal infection, most
likely with an Aspergillus species.
PMID- 25115046
TI - New veterinary graduates: spreading their wings and exploring career paths in
avian and exotic animal medicine.
PMID- 25115045
TI - Tracking migrations of yellow-billed loons (Gavia adamsii) from the Canadian
arctic.
AB - Because the population of yellow-billed loons (Gavia adamsii) is declining,
satellite telemetry was used to learn more about the needs of this species and
the interdependencies of various populations that breed in isolated regions. In
July 2013, the author accompanied a team of biologists to Victoria Island in the
Canadian Arctic to surgically implant satellite transmitters in 14 yellow-billed
loons. This article chronicles the trip with the objective of connecting the
reader with the loons and the interesting people that strive to conserve them.
PMID- 25115047
TI - Rectal adenocarcinoma.
PMID- 25115048
TI - Measuring and reporting service efficiency and effectiveness.
PMID- 25115049
TI - Universal Health Coverage Scheme impact on well-being in rural Thailand.
AB - PURPOSE: The purpose of this paper is to investigate the extent to which the Thai
Universal Healthcare Insurance Coverage Scheme (UC) has contributed to villagers'
well-being in the northeast of Thailand. Public opinion polls specifically
advocate the schemes are used to justify its ongoing political support. However,
the question still remains as to whether it has made a difference in the lives of
poorer rural people. DESIGN/METHODOLOGY/APPROACH: A multi-methods approach and a
well-being focused evaluation (WFE) approach are used to understand villagers'
experiences of having and using the scheme and investigate the villagers'
satisfaction with the scheme and how this satisfaction has contributed to their
life as a whole. FINDINGS: It is found that the scheme had made a valuable
contribution to improving perceived wellbeing amongst villagers. Apart from the
direct benefits of having that healthcare when needed, there is also the indirect
benefit of increasing villagers' sense of security that healthcare will be
accessible if required. RESEARCH LIMITATIONS/IMPLICATIONS: There are still
pertinent issues for policy consideration; for example, almost 31 per cent of the
villagers with the card have never used it. Approximately 22 per cent of people
using the card reported dissatisfactions. Although healthcare direct-costs were
now more affordable, a range of opportunity costs, geographic, social, cultural
and other factors still need to be factored into further policy and service
development to make the scheme more equitable and effective. ORIGINALITY/VALUE:
The study proposes "WFE", a new evaluation approach. WFE may also be applied to
other forms of social policy particularly concerning the impact of its policy on
people's well-being.
PMID- 25115050
TI - Differences in quality of life between pediatric sickle cell patients who used
hydroxyurea and those who did not.
AB - PURPOSE: The purpose of this paper is to examine the differences in quality of
life (QoL) between two groups of pediatric sickle cell patients: those who used
hydroxyurea and those who chose not to use the medication to treat sickle cell
disease. DESIGN/METHODOLOGY/APPROACH: The study was a quantitative, non
randomized, cross-sectional, comparative study. In total, 100 children ages seven
to 17 participated in the study. Parents of the patients completed a demographic
questionnaire while the participants completed the Pediatric Quality of Life
Inventory (Peds QoL) and Sickle Cell Disease Quality of Life Inventory (SCD QoL).
FINDINGS: The Ped QoL regression analysis revealed that hydroxyurea use and
parental marital status accounted for a significant proportion of the variance in
Ped QoL. The SCD QoL regression analysis also revealed that hydroxyurea and age
accounted for a significant proportion of the variance in SCD QoL. Finally, the
regression analysis revealed that SCD, parental marital status, parental income,
sex, age, race and number of siblings did not account for a significant
proportion of the variance in SCD crises per year. ORIGINALITY/VALUE: This paper
proved a need to study the differences in QoL between those pediatric patients
who used hydroxyurea and those who did not use the medication.
PMID- 25115051
TI - Illusion or delusion--Lean management in the health sector.
AB - PURPOSE: There has been considerable interest in the implementation of practices
imported from manufacturing into healthcare as a solution to rising healthcare
spending and disappointing patient safety indicators. One approach that has
attracted particular interest is Lean management and the purpose of this paper is
to engage with this topic. DESIGN/METHODOLOGY/APPROACH: Secondary research.
FINDINGS: Despite widespread enthusiasm about the potential of Lean management
processes, evidence about its contribution to higher organisational performance
remains inconsistent. RESEARCH LIMITATIONS/IMPLICATIONS: This paper engages with
the major Lean concepts of operations management and human resource management,
including just-in-time, total quality management, total productive maintenance
and does not engage in-depth with concepts related to employee empowerment, and
training PRACTICAL IMPLICATIONS: This paper contributes to the organisational
management literature in healthcare by showing that although Lean management
seems to have the potential to improve organisational performance it is far from
a panacea against under performing hospitals. SOCIAL IMPLICATIONS: It informs
policy making by suggesting that a progressive managerial philosophy has a
stronger impact on healthcare performance than the adoption of practices from any
particular managerial approach. ORIGINALITY/VALUE: This paper provides a critical
evaluation of the impact of Lean practices in informing healthcare policy. The
paper contributes to the organisational management literature in healthcare by
showing that even though Lean management in healthcare appears to have the
potential to improve organisational performance; there remain problems with its
application.
PMID- 25115052
TI - An integrated approach for prioritized process improvement.
AB - PURPOSE: The purpose of this paper is to propose an integrated framework to
simultaneously identify and improve healthcare processes that are important from
the healthcare provider's and patient's perspectives.
DESIGN/METHODOLOGY/APPROACH: A modified quality function deployment (QFD) chart
is introduced to the field of healthcare quality assurance. A healthcare service
example is used to demonstrate the utility of the proposed chart. FINDINGS: The
proposed framework is versatile and can be used in a wide variety of healthcare
quality improvement contexts, wherein, two different perspectives are needed to
be considered for identifying and improving critical healthcare processes.
PRACTICAL IMPLICATIONS: The modified QFD chart used in conjunction with the
stacked Pareto chart will facilitate the identification of key performance
metrics from the patient's and the hospital's perspectives. Subsequently, the
chief contributory factors at different levels are identified in a very efficient
manner. ORIGINALITY/VALUE: Healthcare quality improvement professionals will be
able to use the proposed modified QFD chart in association with stacked Pareto
chart for effective quality assurance.
PMID- 25115053
TI - Regulating healthcare complaints: a literature review.
AB - PURPOSE: The purpose of this paper is to explore approaches to the regulation of
healthcare complaints and disciplinary processes. DESIGN/METHODOLOGY/APPROACH: A
literature review was conducted across Medline, Sociological Abstracts, Web of
Science, Google Scholar and the health, law and social sciences collections of
Informit, using terms tapping both the complaints process and regulation
generally. FINDINGS: A total of 118 papers dealing with regulation of health
complaints or disciplinary proceedings were located. The review reveals a shift
away from self-regulation towards greater external oversight, including
innovative regulatory approaches including "networked governance and flexible or
"responsive" regulation. It reports growing interest in adoption of strategic and
responsive approaches to health complaints governance, by rejecting traditional
legal forms in favor of more strategic and responsive forms, taking account of
the complexity of adverse health events by tailoring responses to individual
circumstances of complainants and their local environments. ORIGINALITY/VALUE:
The challenge of how to collect and harness complaints data to improve the
quality of healthcare at a systemic level warrants further research. Scope also
exists for researching health complaints commissions and other "meta-regulatory"
bodies to explore how to make these processes fairer and better able to meet the
complex needs of complainants, health professionals, health services and society.
PMID- 25115054
TI - College clinic service quality and patient satisfaction.
AB - PURPOSE: The purpose of this paper is to identify the service quality dimensions
that play an important role in patient satisfaction in campus clinics in Delhi;
assess student satisfaction with service; and suggests ways to improve areas of
dissatisfaction. DESIGN/METHODOLOGY/APPROACH: A questionnaire was distributed to
students who had completed at least two consultations at the college clinic.
Convenience sampling was used to approach respondents. The questionnaire uses
modified SERVQUAL and other instruments, including original dimensions and those
constructed through detailed discussions. Factor analyses, reliability tests and
the Kaiser-Meyer-Olkin measure of sampling adequacy were conducted. The final
sample had a total of 445 respondents. FINDINGS: After factor analysis, the
authors found that the dimensions affecting patient satisfaction are: staff
professionalism; clinic staff reliability; clinic accessibility and basic
facilities; tangibles; cleanliness; awareness of the clinic/diseases and how
clinic staff deals with emergencies. Most students were satisfied with the
professionalism of the clinic staff. More than 70 percent of the respondents
reported that the clinic staff paid good attention to them. The campus clinic was
deemed reliable by more than 50 percent of respondents. The students found the
clinic's location convenient, with more than 50 percent supporting its location.
However, there was dissatisfaction among the students regarding the tangibles of
the clinic, with more than 50 percent favoring upgrading. There was satisfaction
among the respondents regarding the availability of the doctor after clinic
hours, but contact details for the clinic staff were not easily accessible on
campus. More than 60 percent of respondents were satisfied with the cleanliness
of the campus clinic. More than 50 percent felt that the campus clinic was not
equipped to deal with emergencies efficiently. At the same time, 90 percent of
respondents reported the availability of referral facilities in case of
emergencies. ORIGINALITY/VALUE: The authors believe that this is the first study
conducted to assess patient satisfaction in the campus clinics of engineering
institutes in Delhi region. This paper provides valuable information to college
clinic administrators.
PMID- 25115055
TI - Medical record-keeping and patient perception of hospital care quality.
AB - PURPOSE: Medical record represents the main information support used by
healthcare providers. The purpose of this paper is to examine whether patient
perception of hospital care quality related to compliance with medical-record
keeping. DESIGN/METHODOLOGY/APPROACH: The authors merged the original data
collected as part of a nationwide audit of medical records with overall and
subscale perception scores (range 0-100, with higher scores denoting better
rating) computed for 191 respondents to a cross-sectional survey of patients
discharged from a university hospital. FINDINGS: The median overall patient
perception score was 77 (25th-75th percentiles, 68-87) and differed according to
the presence of discharge summary completed within eight days of discharge (81 v.
75, p = 0.03 after adjusting for baseline patient and hospital stay
characteristics). No independent associations were found between patient
perception scores and the documentation of pain assessment and nutritional
disorder screening. Yet, medical record-keeping quality was independently
associated with higher patient perception scores for the nurses' interpersonal
and technical skills component. RESEARCH LIMITATIONS/IMPLICATIONS: First, this
was a single-center study conducted in a large full-teaching hospital and the
findings may not apply to other facilities. Second, the analysis might be
underpowered to detect small but clinically significant differences in patient
perception scores according to compliance with recording standards. Third, the
authors could not investigate whether electronic medical record contributed to
better compliance with recording standards and eventually higher patient
perception scores. PRACTICAL IMPLICATIONS: Because of the potential consequences
of poor recording for patient safety, further efforts are warranted to improve
the accuracy and completeness of documentation in medical records.
ORIGINALITY/VALUE: A modest relationship exists between the quality of medical
record keeping and patient perception of hospital care.
PMID- 25115056
TI - Essentials of total quality management: a meta-analysis.
AB - PURPOSE: The purpose of this paper is to identify critical successful factors for
Total Quality Management (TQM) implementation. DESIGN/METHODOLOGY/APPROACH: A
literature review was conducted to explore the critical successful factors for
TQM implementation between 1980 and 2010. FINDINGS: A successful TQM
implementation need sufficient education and training, supportive leadership,
consistent support of top management, customer focus, employee involvement,
process management and continuous improvement of processes. RESEARCH
LIMITATIONS/IMPLICATIONS: The review was limited to articles written in English
language during the past 30 years. PRACTICAL IMPLICATIONS: From a practical point
of view, the findings of this paper provide managers with a practical
understanding of the factors that are likely to facilitate TQM implementation in
organisations. ORIGINALITY/VALUE: Understanding the factors that are likely to
promote TQM implementation would enable managers to develop more effective
strategies that will enhance the chances of achieving business excellence.
PMID- 25115057
TI - The role of toll-like receptor agonists in the immunotherapy of leishmaniosis. An
update and proposal for a new form of anti-leishmanial therapy.
AB - The use of toll-like receptor agonists in immunotherapy is a new approach in the
prevention of immunosuppression during fatal Leishmania parasite infection. The
objective of such immunotherapy is to activate specific cell-mediated immune
responses, macrophage activation and antigen-responsive inflammation, to kill
intracellular amastigotes. Toll-like receptor agonist-based treatment in
immunocompetent hosts can be effective either by selective use of the agonists
alone or in combination with the anti-leishmanial drug stibanate. Recent
investigations suggest that toll-like receptor signal pathways constitute a
possible new mode of anti-leishmanial treatment. This article describes the
prospect of toll-like receptor - mediated signal pathways in the immunotherapy of
cutaneous and visceral leishmaniosis, as well as post kala-azar dermal
leishmaniosis (PKADL), a skin-sequel of visceral infection. Suitable synthetic
agonists need to be developed for toll-like receptors to overcome
immunosuppression.
PMID- 25115058
TI - Toxoplasma gondii and the host cells.
AB - The protozoan Toxoplasma gondii, described by Nicolle and Manceaux in 1908, is a
ubiquitous and cosmopolitan parasite that infects a wide range of mammal and bird
species with high prevalence. The biological success of T. gondii is associated
with the formation of a specific relationship between the parasite and host cells
leading to the establishment of a latent, chronic infection. During primary
infection, acquired mostly by the oral route, the quickly multiplying tachyzoites
disseminate through the body crossing several structural-functional barriers as
blood-brain or blood-retina, then they transform into dormant bradyzoites which,
enclosed in tissue cysts, occupy preferentially the brain, skeletal muscle and
eye. Although T. gondii is able to infect all kinds of nucleated cells, it uses
strictly defined host cells, dependent on the life-cycle phase and infection
stage. The article discusses selected aspects of the parasite passing via the
host body barriers as well as particular role of dendritic cells and skeletal
muscle cells, used by the parasite as an very effective vehicle to disseminate
throughout the host body or the site of long-term T. gondii persistence,
respectively.
PMID- 25115059
TI - Hirudotherapy in veterinary medicine.
AB - The saliva of medicinal leeches, e.g., Hirudo medicinalis and Hirudo verbana
commonly used in hirudotherapy, contains more than 100 bioactive substances with
various therapeutic effects, including anticoagulant, vasodilator, thrombolytic,
anti-inflammatory and anaesthetic properties. Recently, leeches have been used
very successfully in veterinary medicine to treat many diseases of animals,
especially dogs, cats and horses. The most common indications for the use of
leeches are hip and elbow dysplasia, acute and chronic arthritis, diseases
associated with inflammation of tendons, ligaments, and fascia, diseases of the
vertebrae and the treatment of scars. Leech therapy is a painless procedure which
takes an average of 30 to 120 minutes, the time being dependent on the size of
the animal. All leeches used in medical procedures should originate only from
certified biofarms. The maintenance of sterile conditions for the culture,
transport and storage of medical leeches is very important to protect animals
from microbial infections. Hirudotherapy is successfully used in veterinary
medicine, especially when traditional treatment is not effective, the effects of
treatment are too slow, or after surgery, when the tissues may be threatened by
venous congestion.
PMID- 25115060
TI - Occurrence of coccidia infection in pigeons in amateur husbandry. Diagnosis and
prevention.
AB - Coccidiosis caused by Eimeria spp. is a common parasitic disease posing a serious
problem in pigeon keeping. The aim of the study was to determine the species
composition, the degree of coccidia infection and the effect of the coccidiostat
used in the course of the disease in two pigeon lofts located in the West
Pomerania province. The material for the study came from 180 birds. A total of
330 faecal samples were investigated with two methods: Willis-Schlaafs
(qualitative) and McMaster's (quantitative). The pigeons were given the Baycox
(Bayer) coccidiostat with toltrazuril as an active substance. The medicament was
administered for two days at a dose of 20 mg/kg body weight at three-day
intervals. Three species of protozoa were isolated: Eimeria labbeana, E.
columbarum, E. columbae, and the infections were mixed. The occurrence of E.
labbeana was most commonly reported, which was shown, depending on the pigeon
loft and the age of the birds, in 89-93% of young pigeons and in 63-55% of
adults. The species E. columbarum and E. columbae were found less frequently.
Baycox coccidiostat proved to be highly effective against coccidiosis in pigeons
and may also be used in prophylaxis.
PMID- 25115062
TI - Chigger mites (Actinotrichida: Parasitengona, Trombiculidae) of Poland. An
updated distribution and hosts.
AB - The existing body of knowledge regarding the Trombiculidae of Poland is
summarized and supplemented with the results of our recent studies. Although
around 3000 nominal species are known worldwide, only 18 have been recorded in
Poland. Due to the medical and veterinary importance of parasitic larvae, and the
complex life cycle which presents difficulties in finding habitats occupied by
postlarval forms, most species have been described exclusively from their larvae.
This review provides updated information on the host spectrum and distribution of
all the trombiculid species hitherto recorded in Poland, supplemented with data
on their general distribution and biology.
PMID- 25115061
TI - Study on the occurrence of tick-borne encephalitis virus RNA in European bison
(Bison bonasus) eliminated at Bialowieza Primeval Forest (north-eastern Poland)
in 2005-2009.
AB - Tick-borne encephalitis virus (TBEV) (Flaviviridae, Flavivirus) is an arthropod
borne virus, an etiologic agent of tick-borne encephalitis (TBE), an infection
involving the central nervous system. The disease is endemic in a large region in
Eurasia where it is transmitted mainly by Ixodes ricinus in Europe and I.
persulcatus ticks in Asia. This is the most important tick-transmitted arbovirus
of human pathogenicity in Europe. The Bialowieza Primeval Forest is a well-known
endemic focus of tick-borne encephalitis. The aim of this study was to identify
the prevalence of tickborne encephalitis virus (TBEV) in European bison, the
important hosts of ticks in the Bialowieza Primeval Forest. In the years 2005
2009, 95 blood samples were collected from European bison and examined for the
presence of TBEV using nRT-PCR method. No positive results were obtained. For
better understanding of TBEV vertebrate reservoir hosts in Poland, further
investigations are needed.
PMID- 25115063
TI - A comparison of FLOTAC and CFF techniques in detecting gastrointestinal parasites
in water buffaloes (Bubalus bubalis).
AB - The objective of the study was to compare the usefulness of FLOTAC and
centrifugal fecal flotation (CFF) techniques. More specifically, the taxonomic
classes (Nematoda and Cestoda) of endoparasites present in fecal samples of
buffaloes are identified, the sensitivity and specificity of FLOTAC relative to
CFF are calculated, and the agreement of both techniques is evaluated using Kappa
statistics. Fresh fecal samples from 220 buffaloes in 10 municipalities were
collected. Sheather's sugar was used as a flotation solution for both the FLOTAC
and CFF techniques. Of the 220 animals, 109 samples were nematode positive and
111 samples were nematode negative according to the FLOTAC technique, while 74
were found to be positive and 146 negative according to the CFF technique. No
cestodes were detected by either technique. The calculated sensitivity for FLOTAC
is 89.19% and its specificity is 70.55%. Kappa statistics revealed moderate
agreement (k = 0.535) between the two techniques in detecting nematodes. The
prevalence observed based on FLOTAC and CFF test were 49.54% (109/220; 95% CI:
47.75-56.34) and 33.64% (72/220; 95% CI: 27.42-40.3), respectively.
PMID- 25115065
TI - Professor James Harlan Steele, DVM (1913-2013). Obituary.
PMID- 25115064
TI - Histopathological diagnosis in parasitic diseases.
AB - Histopathological research is very important in diagnosing human and animal
diseases. Detection of histopathological changes during certain parasitic
invasions is particularly important for differential diagnosis and often confirms
the presence of parasitic diseases. Such studies allow also to conclude on the
primary cause of the disease.
PMID- 25115067
TI - Improved synthesis of (+/-)-trichodiene--a volatile marker for trichothecene
mycotoxins.
AB - Trichodiene is the first and only volatile intermediate in the biosynthesis of
Fusarium mycotoxins and its detection in the gas-phase might therefore be of
potential interest as a marker for food safety analysis. We herein present an
improved diastereoselective synthesis of trichodiene which can be used as an
analytical standard for a headspace gas chromatography / mass spectrometry method
to be developed.
PMID- 25115066
TI - A new source of (R)-limonene and rotundifolone from leaves of Lippia pedunculosa
(verbenaceae) and their trypanocidal properties.
AB - Investigation by GC-FID and GC-MS of the essential oil (LPOE) from the leaves of
Lippia pedunculosa revealed, as the major compounds, the monoterpenes
rotundifolone (71.7%) and (R)-limonene (21.8%). These two compounds and the minor
constituent piperitenone (1.2%) were also isolated from the leaves and identified
by spectrometric analysis. LPOE and isolated compounds were evaluated for their
trypanocidal activity against epimastigote and trypomastigote forms of
Trypanosoma cruzi. Significant results with IC50 values lower than 34.0
microg.mL(-1) were observed against these forms of T. cruzi for LPOE and isolated
compounds. Rotundifolone was the most active compound with an ICso lower than
10.0 ig.mL"' for both forms of T. cruzi. The effects of LPOE and isolated
compounds were also evaluated in cultures of macrophages infected with T. cruzi.
Treatment with (R)-limonene and rotundifolone caused a moderate reduction in the
percentage of macrophages infected by T. cruzi and in the number of intracellular
parasites at concentrations non-toxic to macrophages.
PMID- 25115068
TI - Synthesis and insecticidal activities of novel nitrogenous derivatives of
celangulin-V.
AB - In order to develop new biorational pesticides and clarify the potential
structural factors needed for the biological activity of celangulin-V analogues,
thirty novel nitrogenous derivatives were designed and synthesized. The single
crystal structure of celangulin-V is reported for the first time and provides a
more accurate structure than that previously reported. The structures of all the
new derivatives were confirmed by either NMR or ESI-MSn analysis. Insecticidal
activities of these compounds were tested against the third-instar larvae of
Mythimna separata. One derivative (1-6) showed higher insecticidal activity than
celangulin-V, with a KD50 of 231.2 microg.g(-1), while two compounds (2-13 and 2
14) exhibited lower insecticidal activities; the others revealed no activity at a
concentration of 20 mg mL(-1). The results support the view that celangulin-V has
the potential to be a lead structure of semi-synthetic green insecticides.
PMID- 25115069
TI - An easy way to pyrimidine based nucleoterpenes.
AB - The direct synthesis of N3 substituted pyrimidine nucleoterpenes from uridine,
thymidine, and inosine with C5, C10, and C15 side chains and using DBU as the
base is described. In all cases the reaction proceeded smoothly in very good
yields (85-99%) affording selectively N3 substituted adducts.
PMID- 25115070
TI - Diastereoselective addition of diazomethane to zaluzanin A.
AB - The diastereoselectivity of diazomethane addition to the conjugated double bond
of alpha,beta-unsaturated sesquiterpene lactones was explored using zaluzanin A
(1) as a model. Thus, the absolute configuration of 1 was assured by X-ray
diffraction analysis including evaluation of Flack and Hooft parameters, and by
vibrational circular dichroism spectroscopy of its diacetyl derivative 2, while
the absolute configuration of the diazomethane addition product, zaluzanin A
pyrazoline (3), was determined by evaluation of the 1H NMR chemical shift changes
with respect to 1, and confirmed by X-ray diffraction analysis, again including
evaluation of Flack and Hooft parameters.
PMID- 25115071
TI - Tauroarenarones A and B, new taurine-containing meroterpenoids from the marine
sponge Dysidea sp.
AB - Two new taurine-containing meroterpenoids, both arenarone derivatives,
tauroarenarone A (1) and tauroarenarone B (2), have been isolated from the
Australian marine sponge Dysidea sp. Their structures were established from NMR
spectroscopic data.
PMID- 25115073
TI - Scalarane sesterterpenes from the Paracel Islands marine sponge Hyrtios sp.
AB - A new scalarane sesterterpene, sesterstamide (1), together with four known
sesterterpenes (2-5), were isolated from the Paracel Islands marine sponge
Hyrtios sp. The chemical structures were established on the basis of
spectroscopic analysis and comparison with known compounds. The cytotoxic and
antileishmanial activities of the isolated compounds were also evaluated.
PMID- 25115074
TI - Novel cucurbitane triterpenoids and anti-cholinesterase activities of
constituents from Momordica charantia L.
AB - The C-19 epimers of 5beta,19-epoxycucurbita-6,23(E),25(26)-triene-3f,19-diol (1)
and 5/,19-epoxy-25-methoxycucurbita-6,23-diene-3beta,19-diol (2) along with
(19R,23E)-5beta,19-epoxy-19-methoxycucurbita-6,23,25-trien-3beta-ol (3), (23E)
5beta,19-epoxycucurbita-6,23-diene-3beta,25-diol (4), ligballinol (5), charantin
(6) and momordicoside K(7) were isolated from the green fruits of Momordica
charantia. The (S)-epimers of 1 and 2 are the first reports in nature. The acetyl
and butyryl-cholinesterase inhibitory activities of the isolated compounds were
evaluated, and 5 showed the highest activity of these compounds against
butyrylcholinesterase (IC50 = 32.20 microM) with a reversible and non-competitive
inhibition mode.
PMID- 25115072
TI - Stereo and regioselective microbial reduction of the clerodane diterpene 3,12
dioxo-15,16-epoxy-4-hydroxycleroda-13(16),14-diene.
AB - The biotransformation of the clerodane diterpene, 3,12-dioxo-15,16-epoxy-4
hydroxy-cleroda-13(16),14-diene (1), obtained from Croton micans var.
argyroglossum (Baill.) Mill., was investigated for the first time. Whole cells of
Cunninghamella echinulata and Rhizopus stolonifer were used as enzymatic systems,
and with both fungi the only biotransformation product obtained was the new ent
neo-clerodane diterpene (3R,4S,5S,8S,9R,10S)-3,4-dihydroxy-15,16-epoxy-12-oxo
cleroda-13(16),14-diene (2a). The absolute stereochemistry of 2a was inferred by
comparison of its optical rotation with those of the chemical reduction product
of 1 and its quasienantiomer 2c.
PMID- 25115075
TI - Immunomodulatory action of triterpene glycosides isolated from the sea cucumber
Actinocucumis typica. Structure-activity relationships.
AB - Stimulation of lysosomal activity and ROS formation in mouse peritoneal
macrophages by five triterpene glycosides, typicosides A1 (1), A2 (2), B1 (3), C1
(4) and C2 (5) has been studied and compared with their cytotoxic activities.
Glycosides 1-3 possess moderate activities, but the most cytotoxic glycoside 5 is
not active. Typicoside C1 (4), with low toxicity, was proved to be the most
active concerning stimulation of ROS formation. This is the first example of a
triterpene glycoside from sea cucumbers with low cytotoxicity, but which
demonstrates a strong immunostimulatory effect on mouse peritoneal macrophages in
vitro.
PMID- 25115076
TI - Chromatographic fingerprint combined with content of asperosaponin VI and
antioxidant activity for quality evaluation of wine-fried Dipsaci Radix.
AB - Dipsaci Radix, the dry root of Dipsacusasper Wall. ex Henry, is a commonly used
traditional Chinese medicine (TCM). A novel comprehensive method was proposed for
quality evaluation of wine-fried Dipsaci Radix by an integrated data including
three aspects of information: high performance liquid chromatography (HPLC)
fingerprint, asperosaponin VI content and antioxidant activity (AA). Various
indicators including fingerprint similarity, asperosaponin VI content and AA were
respectively employed for quality assessment of processed Dipsaci Radix samples.
Results showed that considerable differences existed in quality of processed
samples with different processing conditions according to three indicators. Among
the factors affecting quality of wine-fried Dipsaci Radix, heating temperature
was the most influential factor based on analysis of variance (ANOVA), and should
be cautiously controlled. The three evaluation indicators respectively used for
optimization of processing technology suggested different optimal conditions of
wine-frying. Therefore, a combined indicator based on three evaluation indicators
was used for determination of optimal processing condition. Multivariate
statistical methods such as Hierarchical Clustering Analysis (HCA) and Principal
Components Analysis (PCA) were both employed to classify the processed samples
for quality evaluation. To more comprehensively evaluate the quality of wine
fried Dipsaci Radix, HPLC fingerprint combined with content of asperosaponin VI
and AA may be a reasonable and practical approach.
PMID- 25115078
TI - Ring A conformation of aconine and pseudaconine in CDCl3.
AB - On the basis of intensive interpretation of the 1H NMR spectroscopic data, the
ring A conformation of aconine (1) was speculated as twist boat in CDCl3, and as
chair or twist boat in acetone-d6 and pyridine-d5. The ring A of pseudaconine (2)
adopts the chair conformation in CDCl3, acetone-d6, and pyridine-ds. Accordingly,
the boat conformation of ring A in these two diterpenoid alkaloids in CDCl3
reported in the literature [1] should be revised. The difference in 13C NMR data
for the same compound (1 or 2) in two different solvents (CDCl3, pyridine-d5) can
be attributed to solvent effects.
PMID- 25115077
TI - Morphological, chemical and molecular characterization of Centella asiatica
germplasms for commercial cultivation in the Indo-Gangetic plains.
AB - Centella asiatica germplasm collected from north, north-eastern and southern
parts of India was compared for biomass and centellosides productivity under
uniform agro-climatic conditions of the Indo-Gangetic plains at Lucknow. The
highest biomass accumulation (411.9 g FW/m2 area) was recorded in accession A
from north India, followed by 284.0, 135.7 and 29.2 g FW/m2 in accessions M, B
and E from southern, eastern and north-eastern regions, respectively. Accession M
possessed the highest asiaticoside content (52.1 mg/gDW) that was 1.58, 2.34 and
21.7 folds more than accessions A, B and E, respectively. The madecassoside level
in leaves of accessions B and M was comparable (28.9 and 25.7 mg/gDW) and two
folds more than accession A (13.9 mg/gDW). The madecassic and asiatic acid
content in leaf tissue of all four accessions remained low in Lucknow. Amplified
fragment length polymorphism (AFLP) analysis with 23 primers yielded 696
fragments, 563 of which were polymorphic. Accession M out-grouped with genetic
dissimilarity indices of 83, 85 and 95% from accessions A, E and B, respectively.
Commercial cultivation of accessions M and A through a four months growth cycle
(June to September) in agro-climatic conditions of the Indo-Gangetic plains is
suggested.
PMID- 25115079
TI - Revised NMR data for 9-O-demethylgalanthine: an alkaloid from Zephyranthes
robusta (Amaryllidaceae) and its biological activity.
AB - Ongoing studies of Zephyranthes robusta resulted in the isolation of the lycorine
type alkaloid previously called carinatine and 10-O-demethylgalanthine. The NMR
data given previously for this compound were revised and completed by two
dimensional 1H-1H and 1H-13C chemical shift correlation experiments. The name of
the isolated compound was corrected to 9-O-demethylgalanthine in accordance with
the currently used system of numbering of lycorine-type alkaloids. 9-O
Demethylgalanthine and galanthine, a previously isolated alkaloid from Z robusta,
were inactive in acetylcholinesterase/butyrylcholinesterase assays (IC50 > 500
microM), but showed important prolyl oligopeptidase inhibition activity.
PMID- 25115080
TI - Structure revision of N-mercapto-4-formylcarbostyril produced by Pseudomonas
fluorescens G308 to 2-(2-hydroxyphenyl)thiazole-4-carbaldehyde [aeruginaldehyde].
AB - An antibiotic substance isolated from Pseudomonas fluorescens strain G308 was
earlier assigned the structure of N-mercapto-4-formylcarbostyril, but
computational predictions of the 1H and 13C NMR magnetic shielding tensors show
this structure to be incompatible with the published spectroscopic data. The same
is true for six quinoline derivatives related to N-mercapto-4-formylcarbostyril
by permutation of the O and S atoms. In contrast, 2-(2-hydroxyphenyl)thiazole-4
carbaldehyde [aeruginaldehyde], isolated from Pseudomonas protegens Pf-5,
together with the reduced derivative aeruginol, displays spectroscopic data
identical with those of the alleged carbostyril derivative. In addition, the
published 1H and 13C NMR data are in agreement with those calculated for
aeruginaldehyde. We propose that aeruginaldehyde and aeruginol originate from the
non-ribosomal peptide synthetase enzymes involved in the siderophores enantio
pyochelin (or pyochelin) biosynthetic pathways.
PMID- 25115081
TI - Accumulation and function of trigonelline in non-leguminous plants.
AB - As part of our studies of the occurrence, biosynthesis, function and human use of
trigonelline, we looked at trigonelline-accumulating plant species and at the
distribution of trigonelline in different organs of trigonelline-accumulating non
leguminous plants. There are many trigonelline-synthesizing plant species, but
apart from legume seeds only a few species accumulate high concentrations of
trigonelline. We have found only three species that accumulate high levels of
trigonelline: Murraya paniculata (orange jessamine), Coffea arabica (coffee) and
Mirabilisjalapa (four o'clock flower). Trigonelline was found in all parts of
Murraya paniculata seedlings at 4-13 micromol/g fresh weight; more than 70% was
distributed in the leaves. In the coffee plant, trigonelline was found in all
organs, and the concentrations in the upper stems, including tips (48 micromol/g
FW) and seeds (26 micromol/g FW), were higher than in other organs. In Mirabilis
jalapa plants, trigonelline was found in leaves, stems, flowers, roots and seeds;
the concentration varied from 0.3 to 13 micromol/g FW and was generally higher in
young tissues than in mature tissues, except for seeds. Exogenously supplied
nicotinamide increases the trigonelline content. The in planta role of
trigonelline and the possible use oftrigonelline-accumulating plants in herbal
medicine are discussed.
PMID- 25115082
TI - Metabolites of the endophytic fungus Penicillium sp. FJ-1 of Acanthus
ilicifolius.
AB - Two new compounds, named as (2R,3S)-pinobanksin-3-cinnamate (1), and 15alpha
hydroxy-(22E,24R)-ergosta-3,5,8(14),22-tetraen-7-one (2), were isolated from the
endophytic fungus Penicillium sp. FJ-1 of Acanthus ilicifolius Linn. Their
structures were elucidated on the basis of spectroscopic analysis. Additionally,
compound 1 exhibited potent neuroprotective effects on corticosterone-damaged
PC12 cells, and compound 2 showed potent cytotoxicity on glioma cell lines.
PMID- 25115083
TI - Overexpression of cinnamate 4-hydroxylase and 4-coumaroyl CoA ligase prompted
flavone accumulation in Scutellaria baicalensis hairy roots.
AB - Scutellaria baicalensis Georgi, a species of the Lamiaceae family, is considered
as one of the 50 fundamental herbs used in traditional Chinese medicine. In order
to enhance flavone (baicalein, baicalin, and wogonin) content in S. baicalensis
roots, we overexpressed a single gene of cinnamate 4-hydroxylase (C4H) and 4
coumaroyl coenzyme A ligase (4CL) using an Agrobacterium rhizogenes-mediated
system. SbC4H- and Sb4CL-overexpressed hairy root lines enhanced the transcript
levels of SbC4H and Sb4CL compared with those in the control and also increased
flavones contents by approximately 3- and 2.5-fold, respectively. We successfully
engineered the flavone biosynthesis pathway for the production of beneficial
flavones in S baicalensis hairy roots. The importance of upstream gene C4H and
4CL in flavone biosynthesis and the efficiency of metabolic engineering in
promoting flavone biosynthesis in S. baicalensis hairy roots have been indicated
in this study.
PMID- 25115084
TI - New isoflavone glycosides from the stems of Dalbergia vietnamensis.
AB - Two new isoflavone glycosides, dalspinosin 7-O-beta-D-apiofuranosyl-(1-->6)-beta
D-glucopyranoside (1) and caviunin 7-O-(5-O-trans-p-coumaroyl)-beta-D
apiofuranosyl-(1-->6)-beta-D-glucopyranoside (2), and two known compounds,
caviunin 7-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside (3) and caviunin
(4) were isolated from the stems of Dalbergia vietnamensis. Their structures were
determined by the combination of spectroscopic and chemical methods, including 1D
and 2D-NMR spectroscopy, as well as by comparing with the NMR data reported in
the literature.
PMID- 25115085
TI - A characterization of content, composition and scavenging capacity of phenolic
compounds in parsnip roots of various weight.
AB - The contents, composition and radical scavenging capacity of phenolic compounds
from parsnips of various root weights grown in Serbia were examined. The content
of phenolic compounds depended on root size, and the highest content was in the
group where the samples with the lowest root size were grouped. The content of
phenolic compounds varied from 109.7 to 125.3 micromol of chlorogenic acid per g
dry extract, i.e.5470.8 to 6245.1 mg per kg fresh weight. Among the identified
compounds were quercetin, kaempferol, apigenin and genkwanin glucosides and
hydroxycinnamic and caffeoylshikimic acids. The highest antioxidant capacity was
found for the group with the lowest root weight; the IC50 values ranged from 1.59
to 2.49 mg mL(-1). There was positive correlation between the total phenolic
content and scavenging capacity, and the kaempferol glucosides content could be
an indicator of DPPH scavenging capacity of parsnip roots.
PMID- 25115086
TI - Variability of procyanidin type A- and -B trimers content in aerial parts of some
Vaccinium species and cultivars.
AB - Based on the ethnopharmacological data showing that either wild bilberry leaves
or whole aerial parts of the plants have been used as antidiabetic drugs, it can
be hypothesized that the controversial results of various clinical and animal
investigations may be caused by different contents of the active principles in
different aerial parts of the bilberry/blueberry (Vaccinium spp.) plants, as well
as by their geographical and seasonal variability. The aim of this study was to
compare the content of procyanidin type A- and -B trimers in different parts of
wild bilberry (Vaccinium myrtillus L.) and northern highbush blueberry (V.
corymbosum L.) cultivars. Stems (60 samples) and leaves (30 samples) of wild
bilberries and northern highbush blueberry cultivars 'Ama' and 'North Blue' were
collected at different locations in Estonia around the year, and analyzed for the
concentration of the target polyphenols by HPLC-MS/MS. The highest content of
type A doubly linked trimer, a known antidiabetic substance, was established in
the stems of V. myrtillus. These contained up to 100 times more of the active
substance than the leaves of V. myrtillus and at least 1000 times more than the
leaves of V. corymbosum, whereas the seasonal/geographical variation was nearly
tenfold. We suggest using stems of V. myrtillus for future animal and clinical
investigations of bilberry preparations against diabetes.
PMID- 25115087
TI - Three new isoflavonoids from Erythrina caffra.
AB - Three new isoflavonoids, 5,7-dihydroxy-2',4'-dimethoxy-5'-(3-methylbut-2-enyl)
isoflavanone (erycaffra A) (1), 5,7-dihydroxy-2',4'-dimethoxy-5'-(2-hydroxy-3
methylbut-3-enyl)isoflavanone (erycaffra B) (2), and 5,7-dihydroxy-6,8-di-(2
hydroxy-3-methylbut-3-enyl)isoflavone (erycaffra C) (3), were isolated from the
stem bark of E. caffra Thunb., along with eight known compounds, namely,
alpinumisoflavone (4), isoerysenegalensein E (5), beta-amyrin (6), oleanolic acid
(7), octacosyl-E-ferulate (8), triacontyl-4-hydroxycinnamate (9), n-tetracosyl p
coumarate (10) and octacosan-1-ol (11). The structures were determined on the
basis of spectroscopic (1D, 2D-NMR) and MS data and by comparison with literature
values.
PMID- 25115088
TI - Bijayasaline: a new C-glucosyl-alpha-hydroxydihydrochalcone from the heartwood of
Bijayasal (Pterocarpus marsupium).
AB - A new C-glucosyl-alpha-hydroxydihydrochalcone derivative, (aS)-3'-C-ff
glucopyranosyl-a,3,4,2'4'-pentahydroxydihydrochalcone, named as bijayasaline (1)
was isolated from the heartwood of Bijayasal (Pterocarpus marsupium) and
characterized on the basis of NMR and circular dichroism (CD) spectral data.
Bijayasaline (1) showed potent DPPH free radical scavenging activity.
PMID- 25115089
TI - Nelumal A, the active principle of Ligularia nelumbifolia, is a novel aromatase
inhibitor.
AB - Nelumal A, the active principle of Ligularia nelumbifolia was preliminarily
tested as an aromatase inhibitors in HEK293 cells transfected with aromatase cDNA
and using anastrazole as the reference drug. This screening revealed that it
showed an appreciable level of inhibition. Subsequent experiments aimed to
evaluate the aromatase activity and expression in KGN cells confirmed that the
title natural product, after an incubation of 48 h, compared favourably with
anastrazole (1 microM) in the concentration range 10-30 microM. Moreover, nelumal
A (30 microM) abolished the aromatase mRNA expression in the same cell line.
PMID- 25115090
TI - Chemical constituents of Dendrobium venustum and their antimalarial and anti
herpetic properties.
AB - A MeOH extract from the whole plant Dendrobium venustum exhibited significant
antimalarial and anti-herpetic activities. Bioassay-guided isolation of the plant
extract resulted in the isolation of seven known phenolic compounds. Densiflorol
B (3) and phoyunnanin E (6) showed the strongest antimalarial activity and a high
selectivity index, whereas gigantol (2), batatasin III (5) and phoyunnanin C (7)
exhibited moderate activity. Compounds 2 and 5 also showed weak activity against
the Herpes simplex virus. This study is the first report on the chemical and
biological activities of D. venustum.
PMID- 25115091
TI - HPLC-pDA simultaneous determination and protective effect of Anemarrhena
asphodeloides against acute renal failure.
AB - We investigated the protective effects against acute renal failure (ARF) of
Anemarrhena asphodeloides (AA) and performed simultaneous analysis of three
compounds, neomangiferin (1), mangiferin (2), and isomangiferin (3) in AA using a
high-performance liquid chromatography-photodiode array. To measure the
protective effect of ARF, the levels of reactive oxygen species (ROS) and
glutathione depletion were determined using a kit. HPLC analysis was performed
using a Gemini Cia column at 40 degrees C. The mobile phase used gradient elution
with 1.0% (v/v) aqueous acetic acid (A) and 1.0% (v/v) acetic acid in
acetonitrile (B). The flow rate was 1.0 mL/min. In our assay, AA extract inhibits
cisplatin-induced production of intracellular ROS. Pre-incubation of AA extracts
(10-200 microg/mL) markedly maintained cell viability compared with controls in
the noncisplatin-treated cells. Calibration curves of all compounds showed good
linearity (r2 > or = 0.9992). Recoveries of the three compounds were 98.9-103.4%.
The relative standard deviations of intra- and inter-day precision were 0.07
1.73% and 0.12-1.49%, respectively. The amounts of the three components were 1.22
20.63 mg/g. The AA extract has potential as a therapeutic agent for treatment of
ARF. In addition, the established method will help to improve quality control of
AA.
PMID- 25115092
TI - New rocaglamide derivatives from Vietnamese Aglaia species.
AB - Phytochemical analysis of the leaves of different Aglaia species collected in
Vietnam yielded eight rocaglamide derivatives, which are responsible for the
strong insecticidal activity against Spodoptera littoralis, including rocaglamide
A (1), rocaglamide 1 (2), rocaglamide W (3), rocaglamide AB (4), rocaglamide J
(5), rocaglaol (6), rocaglamide S (7) and the new rocaglamide AY (8). The
structures of these compounds were elucidated through extensive 1D and 2D NMR
spectroscopy and analysis of their mass spectrometric (ESI-MS) and HRESIMS data.
PMID- 25115093
TI - Oxirapentyns A, B and E from the marine-derived strain of Isaria felina KMM 4639
as stimulators of initial stages of development of agricultural plants.
AB - Oxirapentyn A (1), oxirapentyn B (2), and oxirapentyn E (3) were examined for
their ability to stimulate growth of seedling roots of barley (Hordeum vulgare
L.), buckwheat (Fagopyrum esculentum Moench), corn (Zea mays L.), soy {Glycine
max (L.) Merr.}, and wheat (Triticum aestivum L.). It was shown that the
stimulatory effects depend on the chemical structure of the oxirapentyns and on
the plant species. Compounds 1, and 2 are efficient for growth of seedling roots
of barley, and wheat, whereas compound 3, at different concentrations, stimulates
growth of seedling roots of maize, soy, and wheat. These compounds can be
recommended for field study as plant growth stimulators.
PMID- 25115094
TI - Concerning the structure of islandoquinone isolated from the lichen Cetraria
islandica.
AB - An investigation of the oxidative coupling products of some substituted
hydroxynaphthazarins led to a revision of the proposed structure of
islandoquinone, previously isolated from the lichen Cetraria islandica, and
yielding (7aS*, 13aS*)-6,7a-diethyl-2,5,9,11,12,13a-hexahydroxy-7, 4
dioxabenzo[a]tetracene-1,4,8,13(7aH, 13aH)-tetraone through X-ray diffraction
analysis of its 2,11-dimethyl ether.
PMID- 25115096
TI - Possible role of fat tissue in the pharmacokinetics of Dodeca-2E,4E,8Z,10E/Z
tetraenoic acid isobutylamides after oral administration of Echinacea
angustifolia extract in rats.
AB - Alkamides are one of the most important constituents of lipophilic extracts of
Echinacea angustifolia roots. These compounds play an important role in the
versatile pharmacological actions of this plant. The present study aimed to
compare the concentrations of isomeric dodeca-2E,4E,8Z,10E/Z-tetraenoic acid
isobutylamides (DTAI) in brain and periepididymal fat tissues and blood plasma of
rats. Thirty, 60, 240 and 720 min after the oral administration of E.
angustifolia root extract, tissue and plasma concentrations were determined by
reversed-phase HPLC with ESI-MS/MS detection. The calculated terminal t1/2 of the
mixture of DTAI was 8.28 h, which indicates a relatively slow elimination. In the
0.5-4 h period the brain/plasma and fat/plasma concentration ratios were
continuously above 3 and 18, respectively, followed by equilibrium at 12 h. Our
results indicate substantial accumulation of alkamides in lipid-rich tissues,
which presumably contributes to a maintained pharmacological action.
PMID- 25115095
TI - Methodology for porphyrin isolation by high-performance countercurrent
chromatography.
AB - Countercurrent chromatography is a versatile technique for the isolation of a
wide variety of plant substances. However, little attention has been devoted to
the application of this technique for the isolation of porphyrins. This class of
compounds are of great importance in the medical area and in photocatalysis due
to their heterocyclic structure, composed of four modified pyrrol subunits
interconnected on their a carbon atoms by methinic bridges. The methanol extract
of Gallesia integrifolia was partitioned using different solvents; the
dichloromethane fraction was then submitted to countercurrent chromatography. The
solvent system composed of n-hexane, ethyl acetate, methanol, and water
(1:2.5:2.5:1) was chosen to perform the chromatographic analysis due to the
enhanced solubility and the best distribution coefficients of the target
compounds. Two porphyrins were isolated by this method and identified as 13(2)
hydroxypheophorbide a methyl ester and pheophorbide a, methyl ester. The solvent
system proposed provided good distribution coefficients for both substances (1.27
and 1.87, respectively), and a high resolution factor.
PMID- 25115097
TI - Ascidian tunicate extracts attenuate rheumatoid arthritis in a collagen-induced
murine model.
AB - Murine rheumatoid arthritis models are often used to investigate the potential
therapeutic effects of candidate drugs. The present study has been conducted in
order to investigate the therapeutic efficacy of ascidian tunicate extracts in a
collagen-induced arthritis DBA1/J mice model. Four types of formulas, ascidian
tunicate extracts (ATE), crude ascidian tunicate glycans (ATEC), ascidian
tunicate extracts with licorice extracts (ATEL), and crude ascidian tunicate
glycans with licorice extracts (ATECL) were orally administered into DBA/1J mice
for 3 weeks and paw edema and thickness were evaluated. Changes in inflammatory
proteins and cytokines levels were monitored in hind leg tissues by Western blot
and quantitative PCR analysis. The oral administration of ascidian tunicate
extracts alleviated paw edema and improved the histological hind leg cartilage
status. The extracts also reduced the matrix metalloproteinase-9 (MMP-9) protein
and prostaglandin E synthase (PGES) levels. In addition, the extracts-treated
groups showed increased interleukin-10 (IL-10) levels compared with the non
treated group. These findings suggest that orally administered ascidian tunicate
extracts might have potential therapeutic effects for the treatment of rheumatoid
arthritis.
PMID- 25115098
TI - Dialyzable leukocyte extracts activate TLR-2 on monocytes.
AB - Dialyzable leukocyte extracts (DLE) transfer specific cell-mediated immune
responses from sensitized donors to non-immune recipients. In addition, DLE have
several immunomodulatory effects and are used for the treatment of several
infectious and non-infectious diseases. Previous studies showed that human DLE
obtained from virus-infected leukocytes and bovine DLE decrease the production of
the pro-inflammatory cytokine TNF-alpha in response to bacterial
lipopolysaccharide, in vitro and in vivo. In the present work, we inquire as to
whether DLE from uninfected human leukocytes have the ability to regulate
cytokine production in peripheral blood mononuclear cells (PBMC) in vitro. We
observed that PBMC from healthy individuals were able to produce TNF-alpha, IL-12
and IL-10 after stimulation with DLE. Moreover, we identified monocytes as the
main cell population that produced TNF-alpha after DLE stimulation.
Interestingly, we found that DLE contain unidentified ligands that activate Toll
like receptor (TLR)-2. Finally, we observed that DLE directly activated monocytes
through TLR-2. These results reveal a new biological activity of DLE, and suggest
that part of the immunomodulatory properties of DLE could be attributed to TLR-2
activation on monocytes and to the induction of a pro-inflammatory environment
that is crucial for control of infectious diseases.
PMID- 25115099
TI - The volatile constituents of Parquetina nigrescens from southwestern Nigeria.
AB - The leaf essential oil of Parquetina nigrescens collected from Badary, Nigeria,
was obtained by hydrodistillation and analyzed by gas chromatography - mass
spectrometry. The essential oil had a simple composition with only five
identified components. The oil was dominated by citral (35.0% neral and 53.7%
geranial). The high concentration of citral in the essential oil likely
contributes to the ethnomedicinal utility and bioactivities associated with this
medicinal plant.
PMID- 25115100
TI - Seasonal variations in the composition of the essential oils of Lavandula
angustifolia (Lamiacae).
AB - Seasonal variations in the composition of the essential oils obtained from the
same individual (of the same genotype) of Lavandula angustifolia cultivated in
Belgrade were determined by GC and GC/MS. The main constituents were 1,8-cineole
(7.1-48.4%), linalool (0.1-38.7%), bomeol (10.9-27.7%), beta-phellandrene (0.5
21.2%) and camphor (1.5-15.8%). Cluster analysis showed that the 21 samples
collected each month during the vegetation cycle were separable into three main
clades with different compositions of essential oils. In the shoots with flowers,
inflorescences and fruits of clade I, linalool is dominant, in the young leaves
before flowering and old leaves of clade II, 1,8-cineole is dominant. In the
young and incompletely developed leaves of clade III, beta-phellandrene is
dominant. The composition of the essential oils of lavender depended on the plant
part and the stage of development.
PMID- 25115101
TI - Chemical composition and antimicrobial activity of the essential oil from Allium
hookeri consumed in Xishuangbanna, southwest China.
AB - The essential oil from the rhizomes of Allium hookeri Thwaites, obtained by
simultaneous distillation extraction, was analyzed by GC-MS. Di-2-propenyl
trisulfide (31.8%), diallyl disulfide (28.4%), and dipropyl trisulfide (8.4%)
were the main constituents among the thirteen identified components. The
essential oil showed strong activity against Aspergillus fumigatus and Candida
albicans with MIC (the minimal inhibitory concentration) and MBC (minimal
bactericidal concentration) values ranging from 32-64 microg/mL. These results
suggest that the essential oil from the rhizomes of A. hookeri could be used as a
potential antimicrobial ingredient in the food industry.
PMID- 25115102
TI - Chemical composition, and cytotoxic, antioxidant and antibacterial activities of
the essential oil from ginseng leaves.
AB - Panax ginseng C.A.Meyer is one of the most valuable traditional Chinese
medicines. In this study, the essential oil of ginseng leaves (EOGL), collected
using hydrodistillation and analyzed by GC/MS, contained a complex mixture of
aliphatic (69.0%), terpenoid (21.5%) and aromatic compounds (2.4%). Among 54
components identified, the major ones were palmitic acid (36.1%), beta-farnesene
(15.4%), linoleic acid (9.8%) and phytol (5.6%). In the cytotoxicity study, EOGL
exhibited obvious cytotoxic activities against different cancer cell lines,
including Hela, A549, ZR-75-1, HT-29, SGC7901 and B16 cells. Furthermore, Annexin
V-FITC/PI staining assay indicated that EOGL can induce late apoptosis of ZR-75-1
cells, and the percentage of apoptotic cells increased in a concentration
dependent manner (0.9% to 5.6% and 67.4%). In addition to this, we also found
that EOGL exhibited weak DPPH radical scavenging (12.0 +/- 0.4 mg/mL) and ABTS
radical scavenging activities (1.6 +/- 0.1 mg/mL), and showed antibacterial
activity against the Gram-positive bacteria, Staphylococcus aureus and Bacillus
subtilis, and the Gram-negative bacterium, Escherichia coli. The data suggest
that EOGL, which possesses important biological activities, especially
significant anticancer activity, could be a potential medicinal resource.
PMID- 25115103
TI - Essential oil from leaves of Liquidambar formosana ameliorates inflammatory
response in lipopolysaccharide-activated mouse macrophages.
AB - The essential oil from Liquidambar formosana leaves (EOLF) was demonstrated to
exhibit anti-inflammatory activity in mouse macrophages. EOLF reduced nitrite
oxide generation, secretion levels of tumor necrosis factor-alpha and interleukin
6, and expression levels of prointerleukin-beta, inducible nitric oxide synthase,
and cyclooxygenase-2 in lipopolysaccharide (LPS)-activated mouse macrophages.
EOLF also reduced NLRP3 inflammasome-derived interleukin-1beta secretion. The
underlying mechanisms for the EOLF-mediated anti-inflammatory activity were (1)
reduction of LPS-induced reactive oxygen species generation; (2) reduction of LPS
induced activation of c-Jun N-terminal kinase, extracellular signal-regulated
kinase, and p38 MAP kinase; (3) reduction of LPS-induced nuclear factor-kappaBeta
activation. Furthermore, 25 compounds were identified in the EOLF using GC-FID
and GC-MS and the major compounds were terpinen-4-ol (32.0%), beta-pinene
(18.0%), gamma-terpinene (13.8%), and alpha-terpinene (9.7%). We found that LPS
induced nitrite oxide generation was inhibited significantly by terpinen-4-ol.
Our results indicated that EOLF has anti-inflammatory activity and may provide a
molecular rationale for future therapeutic interventions in immune modulation.
PMID- 25115104
TI - Accumulation of silicon in cacti native to the United States: characterization of
silica bodies and cyclic oligosiloxanes in Stenocereus thurberi, Opuntia
littoralis, Opuntia ficus-indica, and Opuntia stricta.
AB - Four different cactus species growing in the United States, Stenocereus thurberi
growing in Organ Pipe Cactus National Monument, Arizona, Opuntia littoralis and
Opuntia ficus-indica, growing on Santa Catalina Island, California, and Opuntia
stricta, growing in northern Alabama, were examined for the presence of silica
bodies (opaline phytoliths). Silica bodies were found in all four of these cactus
species, parallelepiped-shaped crystals in S. thurberi, and starburst-shaped
crystalline structures in the three Opuntia species. In addition, the essential
oils of the four cactus species were obtained by hydrodistillation and analyzed
by gas chromatography - mass spectrometry. To our surprise, S. thurberi, O.
littoralis, and O. ficus-indica (but not O. stricta) essential oils contained
cyclic oligosiloxanes. To our knowledge, cyclic oligosiloxanes have not been
previously found as essential oil components.
PMID- 25115105
TI - A phytochemical, pharmacological and clinical profile of Paederia foetida and P.
scandens.
AB - Paederia foetida and P. scandens are two important and well explored Paederia
species (Rubiaceae). P. foetida, which grows mainly in China, Bangladesh, India
and Mauritius, has been used in folk medicine for the treatment of inflammation,
piles, and diarrhea, while P. scandens is used to treat aches, jaundice,
dysentery and dyspepsia as a folk medicine in the southern region of China,
Vietnam, India and Japan. This review covers the comprehensive knowledge of the
traditional medicinal uses, phytochemistry, pharmacology, toxicology and clinical
studies of P. foetida and P. scandens. Phytochemical studies revealed the
presence of iridoids, flavonoids, volatile oil, and other metabolites in these
two species, which possess versatile bioactivities like antinociceptive, anti
inflammatory, antidiarrheal, antitussive and antitumor activities. An injection
developed from P. scandens has been clinically used as an analgesic drug. P.
foetida and P. scandens have emerged as a good source of traditional medicines.
Available scientific references reveal that the biological properties of these
two Paederia species have been evaluated by modem pharmacological studies.
However, bioguided isolation of active constituent responsible for the medical
uses, as well as study of their structure-activity relationship and mode of
actions, is urgently needed.
PMID- 25115106
TI - The oral microbiome in dental caries.
AB - Dental caries is one of the most common chronic and multifactorial diseases
affecting the human population. The appearance of a caries lesion is determined
by the coexistence of three main factors: acidogenic and acidophilic
microorganisms, carbohydrates derived from the diet, and host factors. Socio
economic and behavioral factors also play an important role in the etiology of
the disease. Caries develops as a result of an ecological imbalance in the stable
oral microbiom. Oral microorganisms form dental plaque on the surfaces of teeth,
which is the cause of the caries process, and shows features of the classic
biofilm. Biofilm formation appears to be influenced by large scale changes in
protein expression over time and under genetic control Cariogenic microorganisms
produce lactic, formic, acetic and propionic acids, which are a product of
carbohydrate metabolism. Their presence causes a decrease in pH level below 5.5,
resulting in demineralization of enamel hydroxyapatite crystals and proteolytic
breakdown of the structure of tooth hard tissues. Streptococcus mutans, other
streptococci of the so-called non-mutans streptococci group, Actinomyces and
Lactobacillus play a key role in this process. Dental biofilm is a dynamic,
constantly active metabolically structure. The alternating processes of decrease
and increase of biofilm pH occur, which are followed by the respective processes
of de- and remineralisation of the tooth surface. In healthy conditions, these
processes are in balance and no permanent damage to the tooth enamel surface
occurs.
PMID- 25115108
TI - Modular genetic architecture of the toxigenic plasmid pIS56-63 harboring cry1Ab21
in Bacillus thuringiensis subsp. thuringiensis strain IS5056.
AB - Bacillus thuringiensis subsp. thuringiensis IS5056, a strain highly toxic to
Trichoplusia ni larvae, produces the newly described Cry1Ab21 delta-endotoxin
encoded by a gene located in the 63.8 kb pIS56-63 plasmid. In this report we
present the structure and functional similarity of this plasmid to other B.
thuringiensis large toxigenic plasmids with particular interest focused on its
modular architecture. The 61 open reading frames (ORFs) of the plasmid made four
functional modules: (i) M1-mic, the mobile insertion cassette harboring cry1Ab21;
(ii) M2-tra, the putative conjugative element; (iii) M3-reg, regulation sequence;
and (iv) M4-rep, the ori44 replicon. These modules display similarity to
corresponding sequences in distinct B. thuringiensis plasmids, but, in general,
not to plasmid of other Bacillus cereus sensu lato. The nucleotide sequence and
organization of genes in pIS56-63 were highly similar (80-100%) to those in pHT73
of B. thuringiensis HT73, and in p03 of B. thuringiensis HD771, particularly
within the M3-reg and M4-rep modules, and slightly less in M2-tra, the latter of
which is composed of two segments exhibiting homology to sequences in pBMB28,
pAH187_45, pCT83, and pIS56-85 or to pCT72, pBMB67, p04, and pIS56-68. The
tetrapartite structure of the toxigenic pIS56-63 plasmid strongly suggests that
its hybrid nature is a result of recombination of various genetic elements
originating from different extrachromosomal and chromosomal sources in B.
thuringiensis. The presence of cry1Ab21 in the mobile cassette suggests that its
occurrence on pIS56-63 resulted from recombination and transposition events
during the evolution of the plasmid.
PMID- 25115107
TI - Bacteriophages as an alternative strategy for fighting biofilm development.
AB - The ability of microbes to form biofilms is an important element of their
pathogenicity, and biofilm formation is a serious challenge for today's medicine.
Fighting the clinical complications associated with biofilm formation is very
difficult and linked to a high risk of failure, especially in a time of
increasing bacterial resistance to antibiotics. Bacterial species most commonly
isolated from biofilms include coagulase-negative staphylococci, Staphylococcus
aureus, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Proteus
mirabilis, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp.
The frequent failure of antibiotic therapy led researchers to look for
alternative methods and experiment with the use of antibacterial factors with a
mechanism of action different from that of antibiotics. Experimental studies with
bacteriophages and mixtures thereof, expressing lytic properties against numerous
biofilm-forming bacterial species showed that bacteriophages may both prevent
biofilm formation and contribute to eradication of biofilm bacteria. A specific
role is played here by phage depolymerases, which facilitate the degradation of
extracellular polymeric substances (EPS) and thus the permeation of
bacteriophages into deeper biofilm layers and lysis of the susceptible bacterial
cells. Much hope is placed in genetic modifications of bacteriophages that would
allow the equipping bacteriophages with the function of depolymerase synthesis.
The use of phage cocktails prevents the development of phage-resistant bacteria.
PMID- 25115109
TI - Identification of genomic heterogeneity among Lactococcus lactis strains by
plasmid profiling, PFGE and 16S rDNA sequence analysis.
AB - Lactococcus lactis strains are used commonly as starters, which contribute to
desirable flavour and texture properties known as strain-specific, in dairy
industry. Genomic heterogeneity of 30 L. lactis strains originating from Turkey
and characterized phenotypically were investigated in this study. Plasmid
profiling, PFGE and 16S rDNA sequence analyses were performed to determine the
genetic variability of strains. High degree of heterogeneity was detected among
the L. lactis strains. Plasmid profiles of strains showed that compared to the
plasmid free control strains, namely; L. lactis subsp. lactis IL1403 and L.
lactis subsp. cremoris MG1614, all tested strains carried one to ten plasmids
with molecular size ranging from 1.5 to 41.5kb. The fingerprints of strains
obtained by PFGE from digestion with ApaI, SmaI and I-CeuI restriction
endonucleases of chromosomal DNA's were compared with each other. All strains out
of four were grouped into a large cluster A with at least 44% similarity level.
The other four strains formed a minor duster B, distinctively different from
major cluster A. PFGE results were confirmed by 16S rDNA sequence analysis and
strains included in cluster B were identified as members of different species.
These results suggested that morphologic and biochemical methods should be
verified by reliable molecular approaches for the purpose of strain typing. Also,
PFGE was found suitable to determine genomic differentiations among inter- and
intra species.
PMID- 25115111
TI - Clinical and microbiological evaluation of biofilm-gingival interface
classification in patients with generalized forms of periodontitis.
AB - STUDY OBJECTIVE: In 2008 a new division of periodontal diseases based on the
concept of biofilm-gingival interface (BGI), was presented. The aim of this study
was to assess whether the proposed BGI categories could be useful in diagnosing
patients with generalized forms of both aggressive (gAP) and chronic (gCP)
periodontitis. DESIGN AND KEY METHODS: The study group consisted of 40
individuals (17 with gAP and 23 with gCP). All patients were divided into three
groups according to the BGI scale: 4 patients with P1 (pockets deeper than 4 mms
with bleeding index below 10%), 20 individuals with P2 (pockets deeper than 4 mms
with bleeding index 10-50%) and 16 individuals with P3 (pockets deeper than 4 mms
with bleeding index above 50%). The presence of bacteria in subgingival plaque
was analyzed using the polymerase chain reaction method. RESULTS: Statistically
significant differences with respect to all parameters measured were found when
patients were grouped according to the BGI scale--they were higher in P3 group.
In gAP group A. actinomycetemcomitans and C. rectus were found in a higher
numbers. No such differences were observed between P2 and P3 groups. CONCLUSIONS:
The BGI scale seems to be helpful in effective and quick classifying of patients
into adequate clinical subgroups.
PMID- 25115110
TI - Detection of sulfonamide resistance genes via in situ PCR-FISH.
AB - Due to the rising use of antibiotics and as a consequence of their concentration
in the environment an increasing number of antibiotic resistant bacteria is
observed. The phenomenon has a hazardous impact on human and animal life.
Sulfamethoxazole is one of the sulfonamides commonly detected in surface waters
and soil. The aim of the study was to detect sulfamethoxazole resistance genes in
activated sludge biocenosis by use of in situ PCR and/or hybridization. So far no
FISH probes for the detection of SMX resistance genes have been described in the
literature. We have tested common PCR primers used for SMX resistance genes
detection as FISH probes as well as a combination of in situ PCR and FISH.
Despite the presence of SMX resistance genes in activated sludge confirmed via
traditional PCR, the detection of the genes via microscopic visualization failed.
PMID- 25115112
TI - Microarray analysis of retroviral restriction factor gene expression in response
to porcine endogenous retrovirus infection.
AB - Microarray analysis has been used for screening genes involved in specific
biological processes. Many studies have shown that restriction factors may play
an important role in xenotransplantation safety, but it is still unclear whether
porcine endogenous retroviruses (PERVs) may be inhibited by these factors.
Therefore, the present study focused on the microarray analysis retroviral
restriction factors gene expression in normal human dermal fibroblasts (NHDFs) in
response to PERVs. PERV infectivity was analyzed using a co-culture system of
NHDFs and porcine kidney epithelial cells (PK15 cell line). Detection of the copy
number of PERV A, PERV B DNA and PERV A, PERV B RNA was performed using real-time
Q-PCR and QRT-PCR. The expression of retroviral restriction factor genes was
compared between PERV-infected and uninfected NHDF cells using oligonucleotide
microarray. The up-regulated transcripts were recorded for two differentially
expressed genes (TRIM1, TRIM16) with the use of GeneSpring platform and
Significance Analysis of Microarrays. In conclusion, our results suggest that the
TRIM family may play an important role in innate immunity to PERV infection.
These results can allow a better understanding of restriction mechanism of PERV
infection and probably design molecularly targeted therapies in the future.
Moreover, knowledge of retroviral restriction factor gene expression in human
cells may help to uncover strategies for determining their exact function.
Microarray analyses seem to be promising in biological and biomedical studies,
however, these results should be further confirmed by research conducted at the
protein level.
PMID- 25115113
TI - Molecular analysis of JC polyomavirus genotypes circulating among tribal
populations of North-Eastern West Bengal, India.
AB - There is a resurgence of interest in the study of occurrence, genotype and
pathogenic associations of human Polyomaviruses in recent years. In the present
study, we have ascertained the presence of human Polyomavirus JC (JCV) in the
urine and peripheral blood leukocytes of tribal populations, for the first time
in the North-Eastern part of West Bengal State of India. We have also
characterized the prevalent genotypes of the non-coding controlregions (NCCRs) of
these natural isolates. The result suggests a high incidence of JCV reactivation
in the populations assayed. Approximately 25% of the non-immunocompromized tribal
men and women, tested positive based on polymerase chain reaction (PCR) analysis,
and these results were further confirmed by sequencing of PCR products. Pairwise
sequence comparison and alignment of the NCCR sequence of these Indian strains
appeared to be comparable and related to the archetypal JCV (CY) and the Tibetan
LH3 strains, with some alterations in few key positions. The sequence analyses
were done with regard to transcription factor binding to DNA sequence elements of
endemic JCV NCCRs.
PMID- 25115114
TI - Response of viral specific CD4 T cells to in vitro stimulation with vaccine and
wild measles virus strains in vaccinated and naturally infected subjects.
AB - With the implementation of the WHO strategic plan for the elimination of measles,
the number of measles cases in European Region has decreased. However, outbreaks
are still observed. Although most measles cases affect unvaccinated individuals,
cases with vaccinated persons are also reported. Furthermore, it was described
that a high percentage of young people in Poland exhibit no presence of anti-MeV
IgG despite the high level of vaccination covering no less than 97% of the Polish
population. Strong evidence exists that immunity to measles is complex and
depends on both the humoral and cellular response and although antibodies have
been used as correlates of immunity, it is increasingly being considered that
antibody-based definitions of vaccine success or failure may be incomplete. Here,
we investigated immunity to measles as the reactivity of CD4 T cells to
stimulation with vaccine as well as wild strains of measles virus (MeV) isolated
in Poland, in young vaccinated persons and subjects infected naturally. Evidence
for the presence of MeV-specific memory cells years after infection or
vaccination was found, however the cells ofvaccinees and naturally infected
subjects reacted differently in contact with wild and vaccine MeV strains.
Furthermore, the presence of a significant proportion of non-responder vaccinees
was observed. In conclusion, our results may have implications for studies on the
monitoring of the complexity of post-vaccine immune response.
PMID- 25115116
TI - Trends in antifungal susceptibility of Candida species--one year observation.
AB - In the past years opportunistic fungal infections have seriously increased,
mainly in immunocompromised patients. The aim of the study was to determine the
prevalence of yeast-like fungi in invasive candidiasis and to estimate its
susceptibility to chosen antifungal agents. One hundred and sixty strains of
yeast-like fungi were cultured from various clinical material: samples from lower
respiratory tract, blood, the peritoneal cavity and others. The susceptibility
tests were established according to the quantitative E-test method. The Candida
genus represented the main etiological factor of invasive candidiasis. The
predominant species were: C. glabrata (71/160), C. albicans (34/160), C. krusei
(17/160), C. tropicalis (14/160). All tested strains were the most resistant to
itraconazole. Candida glabrata presented the 100% susceptibility to amphotericin
B and caspofungin and was the least susceptible to itraconazole, posaconazole and
voriconazole. Candida albicans was the most susceptible species to all
antymicotics.
PMID- 25115115
TI - Effects of cryopreservation at -80 degrees C on the formulation and pathogenicity
of the obligate aphid pathogen Pandora nouryi.
AB - Cryopreservation at -80 degrees C is an alternative to liquid nitrogen storage
for Entomophthorales. However, detailed studies about its effects on fungal
pathogenicity and formulation are very limited. In the present study, the
obligate aphid pathogen Pandora nouryi was formulated as mycelia grown on millet
gel granules after preservation as primary spores at -80 degrees C for 3-18
months, although its ability to produce infectious conidia gradually diminished.
The sporulation capacity of this granular formulation was reduced to 18.5 x 10(4)
conidia/mg after 18 months of storage, which was still higher than that of
mycotized aphids. The half-decline time of sporulation capacity was computed as
13.6 months. The infectivity to the green peach aphid Myzus persicae had no
significant decline in 12 months. The ability to yield resting spores within host
carcasses remained unchanged, and the probability of resting spore formation
increased with the conidial concentrations that infect aphids. Therefore,
cryopreservation at -80 degrees C exerted a marginal impact on formulation and
pathogenicity of P. nouryi and can substitute for costly liquid nitrogen storage
in routine laboratory studies. The potential of the formulation in aphid
biocontrol can be maintained although there is a risk of losing fungal
sporulation ability in long-term preservation.
PMID- 25115117
TI - Vasculitis and anaphylactoid shock induced in mice by cell wall extract of the
fungus Candida metapsilosis.
AB - To investigate whether cell wall mannan from Candida metapsilosis induces
vasculitis similar to that in Kawasaki syndrome and anaphylactoid shock in mice,
we examined the pathogenic effects of C. metapsilosis cell wall extracts. Our
results show that intraperitoneal injection of cell wall extracts induced severe
coronary arteritis, and intravenous injection induced acute anaphylactoid shock
similar to extracts from Candida albicans (C. albicans). Structural analysis of
cell wall mannan from C. metapsilosis using NMR spectroscopy showed it to contain
only a-mannan, indicating that a-mannan might be contributing to Candida
pathogenicity by inducing coronary arteritis and acute shock.
PMID- 25115118
TI - Dibasic esters of ortho-/meta-alkoxyphenylcarbamic acid containing 1
dipropylamino-3-piperidinopropan-1-yl and their antimicrobial activity.
AB - In Europe, the presence of microorganisms that have become resistant to
antimicrobials as the most significant disease threat has remained. The aim of
the current research was to screen the in vitro susceptibility of Staphylococcus
aureus, Escherichia coli and Candida albicans to the series of dibasic esters of
ortho-/meta-alkoxyphenylcarbamic acid previously known for their local
anaesthetic effectiveness and to contribute for the structure - antimicrobial
potency relationships study within that class of the compounds. The antimicrobial
activity investigation involved determination of the minimum inhibitory
concentration (MIC) by applying the microdilution method; quantitative screening
was performed on a blood agar (S. aureus), Endo agar (E. coli) or on Sabouraud's
agar (C. albicans). The activity against all the microorganisms tested was
primarily influenced by the position of alkoxy side chain attached to lipophilic
aromatic ring and by its length as well. Inspected meta-alkoxy substituted
derivatives have shown higher efficiency against all chosen microorganisms than
their ortho-alkoxy positional isomers. The most promising results were observed
when investigating the activity of meta-alkoxy substituted molecules against E.
coli with the estimated MICs in the range of 12-49 microg/ml. Furthermore, such
potency was found to be quasi parabolically dependent on alkoxy chain length
achieving a maximum for meta-hexyloxy derivative which has shown MIC= 12
microg/ml. Considered compound was also regarded as the most effective against S.
aureus with MIC = 98 microg/ml. Evaluating the potency against C. albicans, it
was revealed that no molecule within the tested set displayed MIC < 100
microg/ml.
PMID- 25115119
TI - Evaluation of the microbiological quality of conventional and organic leafy
greens at the time of purchase from retail markets in Alexandria, Egypt.
AB - This is a pioneer study in Egypt that provides some assessment of the
microbiological quality of conventional and organic leafy green vegetables that
constitute an essential component of the Egyptians' daily diet. A total of 380
samples of unpackaged whole conventional and 84 packaged whole organic leafy
greens were collected from retail markets in Alexandria, and analyzed for total
aerobic mesophilic count (AMC) and total E. coli count (ECC) using the standard
spread plate method. Mean AMC values for organic samples were statistically less
(p < 0.05) than those of the corresponding conventional samples. Conventional
radish and organic parsley samples had the highest AMC of 7.17 and 7.68 log CFU/g
respectively, while conventional green cabbage and organic basil had the lowest
AMC of 3.63 and 3.23 log CFU/g respectively. The presence of E. coli in 100% of
the studied leafy greens was indicative of potential fecal contamination, in view
of open and unhygienic environmental and unsanitary handling conditions, as leafy
green items are available for sale by street-vendors. Unsatisfactory AMC and ECC
levels encountered in the studied samples, warrant future investigations to
determine the potential prevalence of foodborne pathogens, and to identify
sources of dominating microorganisms, which could make a contribution to the
field of food safety
PMID- 25115120
TI - Definitive assignment by multigenome analysis of the gammaproteobacterial genus
Thermithiobacillus to the class Acidithiobacillia.
AB - The class Acidithiobacillia was established using multiprotein phylogenetic
analysis of all the available genomes of the genus Acidithiobacillus (comprising
Family I, the Acidithiobacillaceae, of the Acidithiobacillales, the order created
for Bergey's Manual of Systematic Bacteriology), and for representative genomes
of all available bacterial orders. The Acidithiobacillales contain a second
family, the Thermithiobacillaceae, represented by Thermithiobacillus tepidarius,
and created on the basis of nearest neighbour 16S ribosomal RNA gene sequence
similarities. This could not be included in the original multiprotein analysis as
no genome sequence for Thermithio bacillus was available. The publication of the
genome sequence of Thermithiobacillus tepidarius in 2013 has enabled phylogenetic
assessment of this organism by comparative multigenome analysis. This shows
definitively that Thermithiobacillus is a member of the class Acidithiobacillia,
distinct from the Acidithiobacillus genus, and confirms it to represent a second
family within the Acidithiobacillia.
PMID- 25115121
TI - Alternative genotyping of drug-resistant Mycobacterium tuberculosis strains.
AB - The aim of the present research was to study the capability of a genotyping
method for M. tuberculosis through detection of six VNTR-loci (MIRU10, MIRU26,
MIRU31, MIRU39, MIRU40, ETR-A). Loci MIRU10, MIRU26, MIRU40 and ETR-A have
exhibited high polymorphism in group non-Beijing, while loci MIRU26 and MIRU31 -
in the Beijing family. A combined detection of all six loci for fingerprinting of
the isolates both from Beijing and non-Beijing was highly effective (Hunter
Gaston index was 0.88 and 0.93 correspondently), especially in areas with limited
financial resources and high prevalence of multidrug resistant M. tuberculosis
strains.
PMID- 25115122
TI - Optimization of culture conditions for exopolysaccharide production by a
probiotic strain of Lactobacillus rhamnosus E/N.
AB - The effects of culture conditions on exopolysaccharides (EPS) production by a
probiotic Lb. rhamnosus E/N have been studied using the Plackett-Burman design.
Process optimization was performed in stationary cultures to maximize the
production of EPS. In order to verify the optimal conditions, an analysis was
performed of EPS production in fermentation culture. Batch fermentation was
carried out at working volume of 2.51. The optimal temperature, pH, carbon
source, and nitrogen source conditions were 37 degrees C, pH 5.0, galactose, and
yeast extract, respectively. EPS production was improved by 210.28 mg/l in
stationary cultures compared to 134.2 mg/l in a control grown on commercial MRS
medium. The fermentor experiment showed the possibility of increasing EPS
biosynthesis by 175.8%. Our results clearly demonstrate that in the case of Lb.
rhamnosus E/N specific culture conditions can enhance EPS production for possible
application in the industry.
PMID- 25115123
TI - Critically appraised topics. 1.5-2 mm of coronal dentin needed for crown buildup
UT CAT #2439.
PMID- 25115125
TI - Why would you want to weight?
PMID- 25115124
TI - Oral and maxillofacial pathology. Case of the month. Myeloid sarcoma with
monocytic differentiation.
PMID- 25115126
TI - Oral cancer.
PMID- 25115127
TI - Routine oral cancer screenings by primary care providers.
PMID- 25115128
TI - Oral cancer screening for asymptomatic adults: do the United States Preventive
Services Task Force draft guidelines miss the proverbial forest for the trees?
PMID- 25115129
TI - Human papillomavirus: the fundamentals of HPV for oral health care providers.
AB - Human papillomavirus (HPV) has become widely known as the causative agent of
cervical cancer and some oropharyngeal cancers. The development of HPV vaccines
has further piqued public interest. As a result, dentists will have increasing
numbers of patients who will inquire about oral HPV infection and its prevention
by means of vaccination. Dental professionals must be informed. This review
provides an overview of HPV, its association with HIV and oropharyngeal cancer,
and information on HPV vaccinations.
PMID- 25115130
TI - Prevalence of HPV associated oropharyngeal cancer among south Texans.
AB - The goal of this study was to begin to assess the prevalence of oropharyngeal
cancer among all oral cancers and thus the potential role of human papillomavirus
(HPV) in this disease in the south Texas Region served by the University of Texas
Health Science Center at San Antonio (UTHSCSA), and University Health System
(UHS) in San Antonio, Texas. This health system represents the largest catchment
area for oral cancer serving the south Texas populations, extending from the U.S.
Mexico border, north to Williamson County, west to Eagle Pass, and east to
Gonzales County. With the move towards electronic medical records (EMR)
nationwide, our team conducted a feasibility study to answer this question
utilizing electronic record coding data across both local networks.
PMID- 25115131
TI - Traits of practices with highy-effective periodontal protocols.
PMID- 25115133
TI - Rapid electrochemical reduction of Ni(II) generates reactive monolayers for
conjugated polymer brushes in one step.
AB - This article reports the development of a robust, one-step electrochemical
technique to generate surface-bound conjugated polymers. The electrochemical
reduction of arene diazonium salts at the surface of a gold electrode is used to
generate tethered bromobenzene monolayers quickly. The oxidative addition of
reactive Ni(0) across the aryl halide bond is achieved in situ through a
concerted electrochemical reduction of Ni(dppp)Cl2. This technique limits the
diffusion of Ni(0) species away from the surface and overcomes the need for
solution deposition techniques which often require multiple steps that result in
a loss of surface coverage. With this electrochemical technique, the formation of
the reactive monolayer resulted in a surface coverage of 1.29 * 10(14)
molecules/cm(2), which is a 6-fold increase over previously reported results
using solution deposition techniques.
PMID- 25115132
TI - Ameliorative effects of Monascus pilosus-fermented black soybean (Glycine max L.
Merrill) on high-fat diet-induced obesity.
AB - The purpose of this study was to examine the antiobesity effects of Monascus
pilosus-fermented black soybean (F-BS) in C57BL/6 mice with high-fat diet (HFD)
induced obesity. F-BS (oral, 0.5 and 1.0 g/kg per body weight, twice per day)
ameliorated obesity by reducing body and liver weight increases, and regulating
blood glucose and cholesterol levels in C57BL/6 mice fed a control or HFD with
oral administration of F-BS for 12 weeks. F-BS suppressed the growth of
epididymal, retroperitoneal, and perirenal fat pads by preventing increases in
the adipocyte size. Moreover, the levels of blood glucose, total cholesterol, and
leptin were significantly lowered by F-BS administration in a dose-dependent
manner. These results indicated that F-BS is a beneficial food supplement for
preventing obesity, controlling blood glucose, and lowering cholesterol. Future
research strategies should address the mechanisms that selectively regulate
obesity, including hyperglycemia and hypercholesterolemia.
PMID- 25115134
TI - Influences of motivational contexts on prescription drug misuse and related drug
problems.
AB - Prescription drug misuse has emerged as a significant problem among young adults.
While the effects of motivational contexts have been demonstrated for illicit
drugs, the role of motivational contexts in prescription drug misuse remains
understudied. Using data from 400 young adults recruited via time-space sampling,
we examined the role of motivational contexts in the frequency of misuse of three
prescription drug types as well as drug-related problems and symptoms of
dependency. Both negative and positive motivations to use drugs are associated
with increases in prescription drug misuse frequency. Only negative motivations
are associated directly with drug problems and drug dependence, as well as
indirectly via prescription pain killer misuse. Addressing positive and negative
motivational contexts of prescription drug misuse may not only provide a means to
reduce misuse and implement harm reduction measures, but may also inform the
content of treatment plans for young adults with prescription drug misuse
problems.
PMID- 25115135
TI - Denial of urinalysis-confirmed opioid use in prescription opioid dependence.
AB - Although research has generally supported the validity of substance use self
reports, some patients deny urine-verified substance use. We examined the
prevalence and patterns of denying urinalysis-confirmed opioid use in a sample of
prescription opioid dependent patients. We also identified characteristics
associated with denial in this population of increasing public health concern.
Opioid use self-reports were compared with weekly urinalysis results in a 12-week
multi-site treatment study for prescription opioid dependence. Among those who
used opioids during the trial (n=246/360), 44.3% (n=109) denied urinalysis
confirmed opioid use, although usually only once (78%). Overall, 22.9% of opioid
positive urine tests (149/650) were denied on self-report. Multivariable analysis
found that initially using opioids to relieve pain was associated with denying
opioid use. These findings support the use of both self-reports and urine testing
in treating prescription opioid dependence.
PMID- 25115137
TI - Germany: Health system review.
AB - This analysis of the German health system reviews recent developments in
organization and governance, health financing, health care provision, health
reforms and health system performance. In the German health care system, decision
making powers are traditionally shared between national (federal) and state
(Land) levels, with much power delegated to self-governing bodies. It provides
universal coverage for a wide range of benefits. Since 2009, health insurance has
been mandatory for all citizens and permanent residents, through either statutory
or private health insurance. A total of 70 million people or 85% of the
population are covered by statutory health insurance in one of 132 sickness funds
in early 2014. Another 11% are covered by substitutive private health insurance.
Characteristics of the system are free choice of providers and unrestricted
access to all care levels. A key feature of the health care delivery system in
Germany is the clear institutional separation between public health services,
ambulatory care and hospital (inpatient) care. This has increasingly been
perceived as a barrier to change and so provisions for integrated care are being
introduced with the aim of improving cooperation between ambulatory physicians
and hospitals. Germany invests a substantial amount of its resources on health
care: 11.4% of gross domestic product in 2012, which is one of the highest levels
in the European Union. In international terms, the German health care system has
a generous benefit basket, one of the highest levels of capacity as well as
relatively low cost-sharing. However, the German health care system still needs
improvement in some areas, such as the quality of care. In addition, the division
into statutory and private health insurance remains one of the largest challenges
for the German health care system, as it leads to inequalities.
PMID- 25115138
TI - Analysis of the Kenyan distance-running phenomenon.
AB - PURPOSE: To investigate the ethnicity of Kenya's most successful international
runners, tracking their evolution over the period of their international
emergence and current dominance. METHODS: The authors analyzed male track
distance events from 800m upwards from all the major global athletics
championships from 1964 to 2013, and the annual Top-25 world marathon
performances since 1990. RESULTS: The percentage of top-25 marathon performances
and medals won by Kenyan and Kalenjin runners have increased over time with Nandi
subtribe outperforming the rest of the world outside Africa (r > .70, large
effect). However, Europe, North America, Oceania, Asia, and South America
decreased over time in top marathon performances and track medals won (r > .70,
large effect). The tribe and subtribe distribution was different in the marathon
than in the track: Maasais were more likely to feature in medals won in shorter
track events than in the top 25 of the world marathon rankings (risk ratio [RR] =
9.67, very large effect). This was also the case for Marakwets (RR = 6.44, very
large effect) and Pokots (RR = 4.83, large effect). On the other hand, Keiyos,
Kikuyus, Kipsigis, Sabaots, and Tugens were more likely to succeed in the
marathon than in shorter track events (RR > 2.0, moderate effect). CONCLUSION:
These data emphasize that the previously documented emergence of African distance
runners is primarily a Kenyan phenomenon, driven by the Kalenjin tribe and in
particular the Nandi subtribe. This supports the complex interaction between
genotype, phenotype, and socioeconomic factors driving the remarkable dominance
of Kenyan distance runners.
PMID- 25115136
TI - Web-based training for primary care providers on screening, brief intervention,
and referral to treatment (SBIRT) for alcohol, tobacco, and other drugs.
AB - This project evaluated a Web-based multimedia training for primary care providers
in screening, brief intervention, and referral to treatment (SBIRT) for unhealthy
use of alcohol, tobacco, and other drugs. Physicians (n = 37), physician
assistants (n = 35), and nurse practitioners (n = 20) were recruited nationally
by email and randomly assigned to online access to either the multimedia training
or comparable reading materials. At baseline, compared to non-physicians,
physicians reported lower self-efficacy for counseling patients regarding
substance use and doing so less frequently. All provider types in both conditions
showed significant increases in SBIRT-related knowledge, self-efficacy, and
clinical practices. Although the multimedia training was not superior to the
reading materials with regard to these outcomes, the multimedia training was more
likely to be completed and rated more favorably. Findings indicate that SBIRT
training does not have to be elaborate to be effective. However, multimedia
training may be more appealing to the target audiences.
PMID- 25115139
TI - Croatia: health system review.
AB - Croatia is a small central European country on the Balkan peninsula, with a
population of approximately 4.3 million and a gross domestic product (GDP) of 62%
of the European Union (EU) average (expressed in purchasing power parity; PPP) in
2012. On 1 July 2013, Croatia became the 28th Member State of the EU. Life
expectancy at birth has been increasing steadily in Croatia (with a small decline
in the years following the 1991 to 1995 War of Independence) but is still lower
than the EU average. Prevalence of overweight and obesity in the population has
increased during recent years and trends in physical inactivity are alarming. The
Croatian Health Insurance Fund (CHIF), established in 1993, is the sole insurer
in the mandatory health insurance (MHI) system that provides universal health
coverage to the whole population. The ownership of secondary health care
facilities is distributed between the State and the counties. The financial
position of public hospitals is weak and recent reforms were aimed at improving
this. The introduction of concessions in 2009 (public private partnerships
whereby county governments organize tenders for the provision of specific primary
health care services) allowed the counties to play a more active role in the
organization, coordination and management of primary health care; most primary
care practices have been privatized. The proportion of GDP spent on health by the
Croatian government remains relatively low compared to western Europe, as does
the per capita health expenditure. Although the share of public expenditure as a
proportion of total health expenditure (THE) has been decreasing, at around 82%
it is still relatively high, even by European standards. The main source of the
CHIFs revenue is compulsory health insurance contributions, accounting for 76% of
the total revenues of the CHIF, although only about a third of the population
(active workers) is liable to pay full health care contributions. Although the
breadth and scope of the MHI scheme are broad, patients must pay towards the
costs of many goods and services, and the right to free health care services has
been systematically reduced since 2003, although with exemptions for vulnerable
population groups. Configuration of capital and human resources in the health
care sector could be improved: for example, homes for the elderly and infirm
persons operate close to maximum capacity; psychiatric care in the community is
not well developed; and there are shortages of certain categories of medical
professionals, including geographical imbalances. Little research is available on
the policy process of health care reforms in Croatia. However, it seems that
reforms often lack strategic foundations and or projections that could be
analysed and scrutinized by the public, and evaluation of reform outcomes is
lacking. The overall performance of the health care system seems to be good,
given the amount of resources available. However, there is a lack of data to
assess it properly.
PMID- 25115140
TI - Major complications of cryoballoon catheter ablation for atrial fibrillation and
their management.
AB - Atrial fibrillation (AF) is the most common symptomatic and sustained cardiac
arrhythmia. It affects approximately 2-3 million people in the USA alone with an
increased incidence and prevalence worldwide. It is associated, in addition to
worsening quality of life, with increased morbidity and mortality especially in
poorly controlled AF, affecting mostly those older than 65 years of age.
Radiofrequency ablation was found to be a good strategy for focal isolation of
pulmonary veins triggering from the vulnerable atrial substrate but is a time
consuming procedure and carries the risk of multiple complications like tamponade
which could be fatal, atrioesophageal fistula and local thrombus formation at the
site of ablation. Cryoballoon ablation with pulmonary vein isolation has emerged
in the past few years as a breakthrough novel technology for the treatment of
drug-refractory AF. It is a relatively simple alternative for point-by-point
radiofrequency ablation of paroxysmal AF and is associated with fewer incidences
of fatal complications such as cardiac perforation. As experience with this new
tool accumulates, the field faces new challenges in the form of rare compilations
including gastroparesis, phrenic nerve palsy, atrioesophageal fistula, pulmonary
vein stenosis, thromboembolism pericardial effusion, and tamponade.
PMID- 25115142
TI - Monitoring neuromuscular fatigue in team-sport athletes using a cycle-ergometer
test.
AB - PURPOSE: To compare a novel sprint test on a cycle ergometer with a
countermovement-jump (CMJ) test for monitoring neuromuscular fatigue after
Australian rules football match play. METHODS: Twelve elite under-18 Australian
rules football players (mean +/- SD age 17.5 +/- 0.6 y, stature 184.7 +/- 8.8 cm,
body mass 75.3 +/- 7.8 kg) from an Australian Football League club's Academy
program performed a short sprint test on a cycle ergometer along with a single
CMJ test 1 h prematch and 1, 24, and 48 h postmatch. The cycle-ergometer sprint
test involved a standardized warm-up, a maximal 6-s sprint, a 1-min active
recovery, and a 2nd maximal 6-s sprint, with the highest power output of the 2
sprints recorded as peak power (PP). RESULTS: There were small to moderate
differences between postmatch changes in cycle-ergometer PP and CMJ PP at 1 (ES =
0.49), 24 (ES = -0.85), and 48 h postmatch (ES = 0.44). There was a substantial
reduction in cycle-ergometer PP at 24 h postmatch (ES = -0.40) compared with 1 h
prematch. CONCLUSIONS: The cycle-ergometer sprint test described in this study
offers a novel method of neuromuscular-fatigue monitoring in team-sport athletes
and specifically quantifies the concentric component of the fatigue-induced
decrement of force production in muscle, which may be overlooked by a CMJ test.
PMID- 25115141
TI - [Septic arthritis in adults].
AB - Septic arthritis is a true rheumatological emergency requiring immediate and
thoughtful effort for rapid diagnosis establishment and treatment initiation.
Children and elderly persons as well as immunocompromised individuals, patients
with pre-existing joint damage and with inflammatory rheumatic joint diseases are
preferentially affected. Bacteremia, joint surgery and intra-articular injections
pose risk situations for the development of joint infections. The most frequent
causative organism is Staphylococcus aureus but other relevant pathogens include
coagulase-negative staphylococci, streptococci and mycobacteria. Synovial fluid
analysis (e.g. appearance, cell count and microbiological examination) is the
most important step to establish the diagnosis. The two main components of
therapy consist of joint drainage and antibiotic treatment. The approach to
periprosthetic joint infections depends on the duration of symptoms, causative
organism and individual factors.
PMID- 25115143
TI - Increased aggression, improved spatial memory, and reduced anxiety-like behaviour
in adult male mice exposed to fluoxetine early in life.
AB - RATIONALE: Fluoxetine (Flx; brand names Prozac, Sarafem, Rapiflux), a selective
serotonin reuptake inhibitor, is prescribed for the treatment of depression in
pregnant women; however, this commonly prescribed medication could affect fetal
brain development as Flx crosses the placenta. The available data concerning the
anatomical and behavioural consequences of perinatal exposure to Flx during early
development on adult behaviour are limited and often contradictory. OBJECTIVES:
To further delineate the long-term behavioural effects of altering 5-HT during
development, we examined the effects of perinatal Flx exposure on the behaviour
of male mice as adults. METHODS: Dams were treated with approximately 25
mg/kg/day of Flx from embryonic day 15 to postnatal day 12, and the behaviour of
the adult offspring was assessed. RESULTS: We found that perinatal Flx exposure
leads to increased aggression, improved spatial memory, and reduced anxiety-like
behaviour. This exposure did not cause memory deficits, changes in sensory
processing, or changes in gross motor function. CONCLUSIONS: Our results suggest
that while perinatal exposure to Flx may have long-term effects on adult
behaviour, these effects appear limited and not necessarily detrimental.
PMID- 25115146
TI - Assessment and monitoring of ballistic and maximal upper-body strength qualities
in athletes.
AB - PURPOSE: To evaluate whether the dynamic strength index (DSI: ballistic peak
force/isometric peak force) could be effectively used to guide specific training
interventions and detect training-induced changes in maximal and ballistic
strength. METHODS: Twenty-four elite male athletes were assessed in the isometric
bench press and a 45% 1-repetition-maximum (1RM) ballistic bench throw using a
force plate and linear position transducer. The DSI was calculated using the peak
force values obtained during the ballistic bench throw and isometric bench press.
Athletes were then allocated into 2 groups as matched pairs based on their DSI
and strength in the 1RM bench press. Over the 5 wk of training, athletes
performed either high-load (80-100% 1RM) bench press or moderate-load (40-55%
1RM) ballistic bench throws. RESULTS: The DSI was sensitive to disparate training
methods, with the bench-press group increasing isometric bench-press peak force
(P=.035, 91% likely), and the ballistic-bench-throw group increasing bench-throw
peak force to a greater extent (P<=.001, 83% likely). A significant increase
(P<=.001, 93% likely) in the DSI was observed for both groups. CONCLUSIONS: The
DSI can be used to guide specific training interventions and can detect training
induced changes in isometric bench-press and ballistic bench-throw peak force
over periods as short as 5 wk.
PMID- 25115145
TI - The European Medicines Agency approval of ingenol mebutate (Picato) for the
cutaneous treatment of non-hyperkeratotic, non-hypertrophic actinic keratosis in
adults: summary of the scientific assessment of the Committee for Medicinal
Products for Human Use (CHMP).
AB - BACKGROUND: The European Commission has recently issued a marketing authorisation
valid throughout the European Union for ingenol mebutate (Picato) in the
cutaneous treatment of non-hyperkeratotic, non-hypertrophic actinic keratosis in
adults. OBJECTIVES: The objective of this paper is to summarise the scientific
review of the application leading to regulatory approval in the EU. The full
scientific assessment report and product information, including the summary of
product characteristics, are available on the EMA website (www.ema.europa.eu).
MATERIAL & METHODS: The application was supported by 25 clinical studies, of
which 18 were performed in patients with actinic keratosis. RESULTS: The active
substance is a pure ingenol angelate obtained from the aerial parts of the plant
species Euphorbia peplus by extraction and purification. One tube of ingenol
mebutate 150 mcg/g gel or 500 mcg/g gel should be applied once daily to the
affected area for 3 or 2 consecutive days on the 'face and scalp' or 'trunk and
extremities', respectively. Complete response rate is 42.2% on the 'face and
scalp' and 34.1% on the 'trunk and extremities'. The most common side effects are
local skin responses including erythema, flaking/scaling, crusting, swelling,
vesiculation/pustulation and erosion/ulceration at the application site.
CONCLUSIONS: The benefits of ingenol mebutate are its ability to improve the
complete response rate of actinic keratosis, the short duration of treatment and
the ease of self-application.
PMID- 25115147
TI - Association between drinking goal and alcohol use one year after residential
treatment: a multicenter study.
AB - This study examined whether patients' drinking goals at admission to and
discharge from 12 residential alcohol use disorder treatment programs were
associated with alcohol-related outcomes at 1-year follow-up. Detoxified patients
(N = 289) completed assessments at admission, after treatment, and at 1-year
follow-up. Drinking goals of abstinence, conditional abstinence (in principle
abstinence but potential occurrence of lapses or drinking, when urges are
strong), and controlled drinking changed during treatment and predicted the 1
year follow-up outcomes (abstinence, number of standard drinks, and number of
days to the first alcohol use). Goals at discharge had a better predictive value.
The goal of abstinence at discharge had better outcomes than conditional
abstinence; the poorest had controlled drinking.
PMID- 25115148
TI - Defining and evaluating the umbrella species concept for conserving and restoring
landscape connectivity.
AB - Conserving or restoring landscape connectivity between patches of breeding
habitat is a common strategy to protect threatened species from habitat
fragmentation. By managing connectivity for some species, usually charismatic
vertebrates, it is often assumed that these species will serve as conservation
umbrellas for other species. We tested this assumption by developing a
quantitative method to measure overlap in dispersal habitat of 3 threatened
species-a bird (the umbrella), a butterfly, and a frog-inhabiting the same
fragmented landscape. Dispersal habitat was determined with Circuitscape, which
was parameterized with movement data collected for each species. Despite
differences in natural history and breeding habitat, we found substantial overlap
in the spatial distributions of areas important for dispersal of this suite of
taxa. However, the intuitive umbrella species (the bird) did not have the highest
overlap with other species in terms of the areas that supported connectivity.
Nevertheless, we contend that when there are no irreconcilable differences
between the dispersal habitats of species that cohabitate on the landscape,
managing for umbrella species can help conserve or restore connectivity
simultaneously for multiple threatened species with different habitat
requirements.
PMID- 25115150
TI - Overview of nongynecological samples prepared with liquid-based cytology medium.
AB - OBJECTIVE: Liquid-based cytology of nongynecological specimens is commonly used
in cytology laboratories throughout the world and various processing methods,
such as ThinPrep and SurePath, have been reported. The cytological features and
performance of liquid-based cytology for various cytology specimens, including
body cavity fluids, urine, brushing specimens and fine-needle aspiration of
various lesions, were reviewed and compared with the experience of our laboratory
and the literature published in PubMed. STUDY DESIGN: The parameters for the
evaluation of liquid-based cytology and conventional smears were described in the
various types of specimens. Criteria for the interpretation of nongynecological
liquid-based cytology were highlighted to show differences in cell morphology,
background and artifacts. RESULTS: The interpretation requires familiarity with
the appearance of liquid-based cytology in the various types of preparations to
avoid misdiagnosis. CONCLUSIONS: Cell blocks can be prepared with specimens
preserved in a liquid-based cytology medium and immunocytochemical stains and
molecular testing can be successfully performed. These are important adjuncts in
order to reach a definitive diagnosis.
PMID- 25115153
TI - Current concepts in cartilage management and rehabilitation.
PMID- 25115149
TI - Systematic review: the combined surgical and medical treatment of fistulising
perianal Crohn's disease.
AB - BACKGROUND: The management of perianal Crohn's fistulas represents a significant
challenge. A combination of medical and surgical therapy, guided by radiology, is
often required. AIM: To review systematically the literature to assess fistula
healing rates with medical treatment (anti-TNF-alpha therapies +/-
immunomodulators) or surgical treatment alone, compared with combined medical and
surgical treatment in fistulising perianal Crohn's disease (CD). METHODS: The
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
guidelines were used. Two independent reviewers searched the literature. RESULTS:
Twenty-four articles were included. The total population was 1139 patients; 460
(40%) received single treatment with either medical or surgical therapy, and 679
(60%) received combined medical and surgical therapy. Eight studies compared
single and combination therapy, with a total population of 797 patients (single
therapy: n = 448, combination therapy: n = 349). In the single therapy group,
191/448 were in complete remission (43%). This was lower than the healing rate of
the combination therapy group 180/349 (52%). No response to therapy was noted in
34% (153/448) of the single therapy group compared with 23% (80/349) of the
combination group. CONCLUSIONS: Combined surgical and medical (anti-TNF-alpha +/-
immunomodulators) therapy may have additional beneficial effects on perianal
fistula healing in patients with Crohn's disease, compared with surgery or
medical therapy alone. A well-designed Crohn's perianal fistula clinical trial is
required in a multidisciplinary medical and surgical setting, with clearly
defined end points of clinical (and likely patient reported outcomes) and
radiological healing.
PMID- 25115151
TI - Serum salusin-alpha and salusin-beta levels in patients with Behcet's disease.
AB - BACKGROUND: Behcet's disease (BD) is a chronic, relapsing, systemic vasculitis of
unknown etiology. There is an increased predisposition to insulin resistance and
metabolic syndrome (MetS) in BD patients. OBJECTIVE: The aim of this study was to
determine serum salusin-alpha and salusin-beta levels in BD patients and healthy
controls and to investigate their association with MetS. PATIENTS AND METHODS:
Twenty-five BD patients and 25 healthy controls were included in the study.
Salusin-alpha and salusin-beta levels were measured in blood samples using ELISA.
In addition, BD patients and healthy controls were evaluated in terms of MetS.
RESULTS: The mean serum salusin-alpha level in BD patients was significantly
lower compared to healthy controls (p = 0.03), whereas the mean serum salusin
beta level in BD patients was significantly higher compared to healthy controls
(p = 0.03). The mean serum salusin-alpha level was significantly lower in BD
patients with MetS compared to BD patients without MetS (p = 0.04). CONCLUSIONS:
Serum salusin-alpha level (an anti-atherogenic molecule) was lower, while serum
salusin-beta level (a pro-atherogenic molecule) was higher in BD patients. We
consider that the decrease in salusin-alpha and the increase in salusin-beta
levels contribute to the development of MetS.
PMID- 25115154
TI - A systematic review of reporting of rehabilitation in articular-cartilage-repair
studies of third-generation autologous chondrocyte implantation in the knee.
AB - CONTEXT: Autologous chondrocyte implantation (ACI) is a tissue-engineered
surgical technique initially developed for articular cartilage repair of isolated
chondral lesions of the knee. Third-generation techniques (ACI3) are now
available that deliver autologous cultured chondrocytes into the defect using
cell scaffolds. The successful outcomes of these techniques have some dependency
on presurgical and postsurgical patient rehabilitation. OBJECTIVES: To determine
if the standard of reporting for rehabilitation has improved in ACI3 studies;
previous reviews in this field recommended describing the detail of this
rehabilitation and patient compliance as integral elements. EVIDENCE ACQUISITION:
A computerized search was performed in March 2013. Criteria for inclusion were
any studies that evaluated or described the process of ACI3 in the knee and
subsequent rehabilitation. The modified Coleman Methodology Score (CMS) was used
to rate the standard of reporting of rehabilitation and surgical procedures;
review articles were also evaluated for quality using the Strength of
Recommendation Taxonomy (SORT). Mean scores, odds ratios, 95% confidence
intervals, and Mann-Whitney U statistics were calculated. EVIDENCE SYNTHESIS: An
improvement in mean CMS was seen compared with previous reviews, but
rehabilitation reporting scores were lower than their surgical equivalent;
significant association was seen between studies with rehabilitator involvement
and high scores in the individual CMS rehabilitation element. Predominant SORT
scores of 2A indicated medium strength of recommendation. CONCLUSIONS: The CMS
provides a general overview of methodological quality, but a more specialized
tool to report on the quantitative and qualitative aspects of the rehabilitation
process would help raise the standards. It is recommended that rehabilitation
therapists be included as key members of research teams and be involved in the
design, implementation, and reporting of future studies.
PMID- 25115156
TI - Management of osteochondritis dissecans of the knee.
AB - The etiology of osteochondritis dissecans is hypothesized as repetitive
microtrauma, resulting in an interruption of blood supply. Due to the location of
the most common lesions on the medial femoral condyle, impingement of either the
medial tibial spine or inferior pole of the patella against the adjacent medial
femur may be responsible. It is much more common in athletic males than other
groups. This article reviews the current treatment options for lesions around the
knee.
PMID- 25115157
TI - The progression of isokinetic knee strength after matrix-induced autologous
chondrocyte implantation: implications for rehabilitation and return to activity.
AB - CONTEXT: Matrix-induced autologous chondrocyte implantation (MACI) is an
established technique for the repair of knee chondral defects. Despite the
reported clinical improvement in knee pain and symptoms, little is known on the
recovery of knee strength and its return to an appropriate level compared with
the unaffected limb. OBJECTIVE: To investigate the progression of isokinetic knee
strength and limb symmetry after MACI. DESIGN: Prospective cohort. SETTING:
Private functional rehabilitation facility. PATIENTS: 58 patients treated with
MACI for full-thickness cartilage defects to the femoral condyles. INTERVENTION:
MACI and a standardized rehabilitation protocol. MAIN OUTCOME MEASURES:
Preoperatively and at 1, 2, and 5 y postsurgery, patients underwent a 3
repetition-maximum straight-leg raise test, as well as assessment of isokinetic
knee-flexor and -extensor torque and hamstring:quadriceps (H:Q) ratios.
Correlation analysis investigated the association between strength and pain,
demographics, defect, and surgery characteristics. Linear-regression analysis
estimated differences in strength measures between the operated and nonoperated
limbs, as well as Limb Symmetry Indexes (LSI) over time. RESULTS: Peak knee
extension torque improved significantly over time for both limbs but was
significantly lower on the operated limb preoperatively and at 1, 2, and 5 y.
Mean LSIs of 77.0%, 83.0%, and 86.5% were observed at 1, 2, and 5 y,
respectively, while 53.4-72.4% of patients demonstrated an LSI < or = 90% across
the postoperative timeline. Peak knee-flexion torque was significantly lower on
the operated limb preoperatively and at 1 year. H:Q ratios were significantly
higher on the operated limb at all time points. CONCLUSIONS: While peak knee
flexion and hip-flexor strength were within normal limits, the majority of
patients in this study still demonstrated an LSI for peak knee-extensor strength
< or = 90%, even at 5 y. It is unknown how this prolonged knee-extensor deficit
may affect long-term graft outcome and risk of reinjury after return to activity.
PMID- 25115158
TI - Quadriceps femoris strength and sagittal-plane knee biomechanics during stair
ascent in individuals with articular cartilage defects in the knee.
AB - CONTEXT: Few objective data are available regarding strength and movement
patterns in individuals with articular cartilage defects (ACDs) of the knee.
OBJECTIVES: To test the following hypotheses: (1) The involved limb of
individuals with ACDs would demonstrate lower peak knee-flexion angle, peak
internal knee-extension moment, and peak vertical ground-reaction force (vGRF)
than the contralateral limb and healthy controls. (2) On the involved limb of
individuals with ACDs, quadriceps femoris strength would positively correlate
with peak knee-flexion angle, peak internal knee-extension moment, and peak vGRF.
DESIGN: Cross-sectional. SETTING: Biomechanics research laboratory. PARTICIPANTS:
11 individuals with ACDs in the knee who were eligible for surgical cartilage
restoration and 10 healthy controls. METHODS: Quadriceps femoris strength was
quantified as peak isometric knee-extension torque via an isokinetic dynamometer.
Sagittal-plane knee kinematics and kinetics were measured during the stance phase
of stair ascent with 3-dimensional motion analysis. MAIN OUTCOME MEASURES:
Quadriceps strength and knee biomechanics during stair ascent were compared
between the involved and contralateral limbs of participants with ACD (paired t
tests) and with a control group (independent-samples t tests). Pearson
correlations evaluated relationships between strength and stair-ascent
biomechanics. RESULTS: Lower quadriceps strength and peak internal knee-extension
moments were observed in the involved limb than in the contralateral limb (P <
.01) and the control group (P < .01). For the involved limb of the ACD group,
quadriceps femoris strength was strongly correlated (r = .847) with involved-limb
peak internal knee-extension moment and inversely correlated (r = -.635) with
contralateral peak vGRF. CONCLUSIONS: Individuals with ACDs demonstrated deficits
in quadriceps femoris strength with associated alterations in movement patterns
during stair ascent. The results of this study are not comprehensive; further
research is needed to understand the physiological characteristics, activity
performance, and movement quality in this population.
PMID- 25115160
TI - Training recruiters to randomized trials to facilitate recruitment and informed
consent by exploring patients' treatment preferences.
AB - BACKGROUND: Patients' treatment preferences are often cited as barriers to
recruitment in randomized controlled trials (RCTs). We investigated how RCT
recruiters reacted to patients' treatment preferences and identified key
strategies to improve informed decision-making and trial recruitment. METHODS:
Audio-recordings of 103 RCT recruitment appointments with 96 participants in
three UK multicenter pragmatic RCTs were analyzed using content and thematic
analysis. Recruiters' responses to expressed treatment preferences were assessed
in one RCT (ProtecT - Prostate testing for cancer and Treatment) in which
training on exploring preferences had been given, and compared with two other
RCTs where this specific training had not been given. RESULTS: Recruiters
elicited treatment preferences similarly in all RCTs but responses to expressed
preferences differed substantially. In the ProtecT RCT, patients' preferences
were not accepted at face value but were explored and discussed at length in
three key ways: eliciting and acknowledging the preference rationale, balancing
treatment views, and emphasizing the need to keep an open mind and consider all
treatments. By exploring preferences, recruiters enabled participants to become
clearer about whether their views were robust enough to be sustained or were
sufficiently weak that participation in the RCT became possible. Conversely, in
the other RCTs, treatment preferences were often readily accepted without further
discussion or understanding the reasoning behind them, suggesting that patients
were not given the opportunity to fully consider all treatments and trial
participation. CONCLUSIONS: Recruiters can be trained to elicit and address
patients' treatment preferences, enabling those who may not have considered trial
participation to do so. Without specific guidance, some RCT recruiters are likely
to accept initial preferences at face value, missing opportunities to promote
more informed decision-making. Training interventions for recruiters that
incorporate key strategies to manage treatment preferences, as in the ProtecT
study, are required to facilitate recruitment and informed consent. TRIAL
REGISTRATION: ProtecT RCT: Current Controlled Trials ISRCTN20141297. The other
two trials are registered but have asked to be anonymized.
PMID- 25115162
TI - The renin-angiotensin system: a possible contributor to migraine pathogenesis and
prophylaxis.
AB - The presence of a tissue-based renin-angiotensin system, independent of the
systemic one, has been identified in several organs including the brain.
Experimental models have suggested the involvement of the renin-angiotensin
system in neurogenic inflammation, susceptibility to oxidative stress,
endothelial dysfunction, and neuromodulation of nociceptive transmission, thus
potentially contributing to the pathogenesis of migraine. Genetic factors that
increase susceptibility to migraine may include angiotensin-converting enzyme
polymorphism, although available data are controversial. Clinical studies have
suggested that angiotensin-converting enzyme inhibitors and angiotensin receptor
blockers may be effective in migraine prophylaxis. However, further research
should clarify whether the postulated preventive effect is attributable to a
pharmacological action over and above the antihypertensive effect and should test
their tolerability in subjects with normal blood pressure values. In patients
with contraindications or not responding to conventional prophylactic drugs and
in patients with comorbid arterial hypertension, angiotensin-converting enzyme
inhibitors and angiotensin receptor blockers may be used for migraine
prophylaxis.
PMID- 25115161
TI - Pigmentation in Drosophila melanogaster reaches its maximum in Ethiopia and
correlates most strongly with ultra-violet radiation in sub-Saharan Africa.
AB - BACKGROUND: Pigmentation has a long history of investigation in evolutionary
biology. In Drosophila melanogaster, latitudinal and altitudinal clines have been
found but their underlying causes remain unclear. Moreover, most studies were
conducted on cosmopolitan populations which have a relatively low level of
genetic structure and diversity compared to sub-Saharan African populations. We
investigated: 1) the correlation between pigmentation traits within and between
the thorax and the fourth abdominal segment, and 2) their associations with
different geographical and ecological variables, using 710 lines belonging to 30
sub-Saharan and cosmopolitan populations. RESULTS: Pigmentation clines
substantially differed between sub-Saharan and cosmopolitan populations. While
positive correlations with latitude have previously been described in Europe,
India and Australia, in agreement with Bogert's rule or the thermal melanism
hypothesis, we found a significant negative correlation in Africa. This
correlation persisted even after correction for altitude, which in its turn
showed a positive correlation with pigmentation independently from latitude. More
importantly, we found that thoracic pigmentation reaches its maximal values in
this species in high-altitude populations of Ethiopia (1,600-3,100 m). Ethiopian
flies have a diffuse wide thoracic trident making the mesonotum and the head
almost black, a phenotype that is absent from all other sub-Saharan or
cosmopolitan populations including high-altitude flies from Peru (~3,400 m).
Ecological analyses indicated that the variable most predictive of pigmentation
in Africa, especially for the thorax, was ultra-violet (UV) intensity, consistent
with the so-called Gloger's rule invoking a role of melanin in UV protection.
CONCLUSION: Our data suggest that different environmental factors may shape
clinal variation in tropical and temperate regions, and may lead to the evolution
of different degrees of melanism in different high altitude populations in the
tropics.
PMID- 25115164
TI - Effect of multivitamin versus multivitamin-mineral supplementation on metabolic
profiles and biomarkers of oxidative stress in pregnant women: a double-blind
randomized clinical trial.
AB - Abstract Objective: This study was designed to determine the favorable effects of
received multivitamin versus multivitamin-mineral supplements on metabolic
profiles and biomarkers of oxidative stress among Iranian pregnant women.
Methods: This double-blind randomized-controlled clinical trial was conducted
among 70 pregnant women, primigravida, aged 18-35 years old between 16 and 37
weeks gestation. Subjects were randomly assigned to receive either the
multivitamin (n = 35) or multivitamin-mineral supplements (n = 35) for 20 weeks.
Fasting blood samples were taken at baseline and after a 20-week intervention to
measure lipid profiles and biomarkers of oxidative stress. Results: After 20
weeks of intervention, multivitamin-mineral supplementation resulted in a
significant difference on serum triglycerides levels (changes from baseline in
multivitamin-mineral group: +6.1 versus in multivitamin group: +45.9 mg/dl, p =
0.04) compared with the multivitamin group. In addition, increased concentrations
of serum HDL-cholesterol (changes from baseline in multivitamin-mineral group:
+0.1 versus in multivitamin group: -7.4 mg/dl, p = 0.02) and total glutathione
(GSH) levels (changes from baseline in multivitamin-mineral group: +151.09 versus
in multivitamin group: -116.21 umol/l, p = 0.003) were also seen in the
multivitamin-mineral group compared with the multivitamin group. Conclusion:
Supplementation of multivitamin-mineral compared to multivitamin supplementation
for 20 weeks during pregnancy had beneficial effects on triglycerides, HDL
cholesterol and GSH levels.
PMID- 25115165
TI - Nutritional practice effectiveness to achieve adequate plasma vitamin A, E and D
during the early postnatal life in Tunisian very low birth weight infants.
AB - Abstract Objective: To look at changes in plasma vitamin A, E and D
concentrations during the early postnatal life and to study their link with
growth and mortality in Tunisian very low birth weight (VLBW) infants. Patients
and methods: A cohort of 607 VLBW infants had been followed from birth until
hospital discharge or death. Blood was collected at birth, at time of maximal
weight loss and at time of recovering birth weight. Retinol and alpha-tocopherol
were analyzed using HPLC and 25 hydroxy vitamin D using radioimmunoassay.
Results: Vitamin A, D and E deficiencies were very common at birth (75.9%, 74.1%
and 65.2%, respectively). The prevalence's have decreased throughout hospital
stay, but remained high at time of recovering birth weight (59.4%, 31.2% and
28.8%, respectively). Vitamin A deficiency was associated with longer hospital
stay [OR (95% CI), 1.66 (1.03-2.93)] and vitamin E deficiency was associated with
increased neonatal mortality [1.44 (1.01-2.23)]. Conclusions: Current nutritional
practices are ineffective to achieve adequate vitamins A, E and D status in
Tunisian VLBW infants during the early postnatal life and should be revised.
Further work is needed to establish recommended doses of vitamins supplements in
these preterm infants.
PMID- 25115166
TI - Randomized trial of intensive motivational interviewing for methamphetamine
dependence.
AB - An intensive, 9-session motivational interviewing (IMI) intervention was assessed
using a randomized clinical trial of 217 methamphetamine (MA) dependent
individuals. Intensive motivational interviewing (IMI) was compared with a single
standard session of MI (SMI) combined with eight nutrition education sessions.
Interventions were delivered weekly over 2 months. All study participants also
received standard outpatient group treatment three times per week. Both study
groups showed significant decreases in MA use and Addiction Severity Index drug
scores, but there were no significant differences between the two groups.
However, reductions in Addiction Severity Index psychiatric severity scores and
days of psychiatric problems during the past 30 days were found for clients in
the IMI group but not the SMI group. SMI may be equally beneficial to IMI in
reducing MA use and problem severity, but IMI may help alleviate co-occurring
psychiatric problems that are unaffected by shorter MI interventions. Additional
studies are needed to assess the problems, populations, and contexts for which
IMI is effective.
PMID- 25115167
TI - Laparoscopic versus open partial nephrectomy for multilocular cystic renal cell
carcinoma: a direct comparison based on single-center experience.
AB - OBJECTIVES: To compare the treatment of laparoscopic (LPN) versus open partial
nephrectomy (OPN) in patients with multilocular cystic renal cell carcinoma
(MCRCC). METHODS: Thirty-seven patients diagnosed with MCRCC were reviewed
retrospectively between January 2007 and January 2013 at our institution. They
were divided into two groups: group 1 (LPN) consisted of 19 patients (51.4%) and
group 2 (OPN) of 18 patients (48.6%). RENAL and the Preoperative Aspects and
Dimensions Used for an Anatomical classification were applied to predict
perioperative complications, which were graded based on the Clavien-Dindo
classification. RESULTS: The two groups were comparable with regard to all of the
patients' baseline characteristics. In group 1, the mean operative time was 142.1
min, including the mean warm ischemia time (WIT) of 32.6 min; the mean estimated
blood loss (EBL) was 96.1 ml, the mean retroperitoneal drainage lasted 3.6 days,
and the mean postoperative hospital stay was 5.3 days. In group 2, the figures
were 126.6 and 23.5 min, 223.3 ml, and 4.6 and 8.7 days, respectively. The
differences in WIT, EBL, drainage days and hospitalization were statistically
significant between both groups (p < 0.05). No recurrence or new lesions occurred
in these patients during a mean follow-up of 37.8 months. CONCLUSIONS: Our single
center experience suggests that although it remains technically complex,
demanding and challenging for MCRCC, LPN can still induce favorable perioperative
results and survival rates in MCRCC are comparable with OPN.
PMID- 25115163
TI - Maternal plasma fetuin-A concentration is lower in patients who subsequently
developed preterm preeclampsia than in uncomplicated pregnancy: a longitudinal
study.
AB - Objective: Fetuin-A is a negative acute phase protein reactant that acts as a
mediator for lipotoxicity, leading to insulin resistance. Intravascular
inflammation and insulin resistance have been implicated in the mechanisms of
disease responsible for preeclampsia (PE). Maternal plasma concentrations of
fetuin-A at the time of diagnosis of preterm PE are lower than in control
patients with a normal pregnancy outcome. However, it is unknown if the changes
in maternal plasma fetuin-A concentrations precede the clinical diagnosis of the
disease. We conducted a longitudinal study to determine whether patients who
subsequently developed PE had a different profile of maternal plasma
concentrations of fetuin-A as a function of gestational age (GA) than those with
uncomplicated pregnancies. Methods: A longitudinal case-control study was
performed and included 200 singleton pregnancies in the following groups: (1)
patients with uncomplicated pregnancies who delivered appropriate for gestational
age (AGA) neonates (n = 160); and (2) patients who subsequently developed PE (n =
40). Longitudinal samples were collected at each prenatal visit and scheduled at
4-week intervals from the first or early second trimester until delivery. Plasma
fetuin-A concentrations were determined by ELISA. Analysis was performed using
mixed-effects models. Results: The profiles of maternal plasma concentrations of
fetuin-A differ between PE and uncomplicated pregnancies. Forward analysis
indicated that the rate of increase of plasma fetuin-A concentration in patients
who subsequently developed PE was lower at the beginning of pregnancy (p =
0.001), yet increased faster mid-pregnancy (p = 0.0017) and reached the same
concentration level as controls by 26 weeks. The rate of decrease was higher
towards the end of pregnancy in patients with PE than in uncomplicated
pregnancies (p = 0.002). The mean maternal plasma fetuin-A concentration was
significantly lower in patients with preterm PE at the time of clinical diagnosis
than in women with uncomplicated pregnancies (p < 0.05). In contrast, there were
no significant differences in maternal plasma fetuin-A concentration in patients
who developed PE at term. Conclusions: (1) The profile of maternal plasma
concentrations of fetuin-A over time (GA) in patients who develop PE is different
from that of normal pregnant women; (2) the rate of change of maternal plasma
concentrations of fetuin-A is positive (increases over time) in the midtrimester
of normal pregnancy, and negative (decreases over time) in patients who
subsequently develop PE; (3) at the time of diagnosis, the maternal plasma fetuin
A concentration is lower in patients with preterm PE than in those with a normal
pregnancy outcome; however, such differences were not demonstrable in patients
with term PE.
PMID- 25115169
TI - Left ventricular pacing in neonates and infants with isolated congenital complete
or advanced atrioventricular block: short- and medium-term outcome.
AB - AIMS: Right ventricular (RV) pacing may induce left ventricular (LV) dysfunction:
neonates and infants with isolated congenital complete/advanced atrioventricular
block (CCAVB) are at high risk of developing RV pacing-induced LV dyssynchrony,
remodelling, and dysfunction. We prospectively investigated whether LV pacing
results in normal LV function and good clinical status in the short/medium term.
METHODS AND RESULTS: In this single-centre, prospective study, 10 consecutive
patients with CCAVB (median age 4 months, range: 0.1-16) underwent pacemaker
implantation (4 VVIR, 6 DDD) using epicardial leads (on the LV apex in 8, on the
LV free wall in 2). Data were collected at implantation and at 1- and 12-month
follow-up. Echocardiographic evaluation included two-dimensional/three
dimensional assessment of LV dimensions, function (ejection fraction, EF), and
ventricular synchrony (interventricular and intraventricular dyssynchrony). Prior
to pacemaker implantation, EF was normal in six patients, 50% in two, <=40% in
two. All patients showed good clinical status and normal LV dimensions at follow
up. Patients with LV dilatation and impaired EF at implantation showed LV reverse
remodelling and enhanced LV function. Normal LV function and synchrony were
observed in most patients (one patient with EF 53% and three patients with mild
dyssynchrony at 12-month follow-up). Paced QRS complex tended to be wider than
native QRS complexes (P = 0.07); QTc duration of paced complexes was within
normal limits or only slightly prolonged, without significant differences
compared with QTc interval of native complexes. CONCLUSION: At short- and medium
term follow-up, LV pacing results in satisfactory LV electromechanical function
and synchrony in neonates and infants with CCAVB.
PMID- 25115170
TI - A descriptive study of elderly patients with dementia who died wandering outdoors
in Kochi Prefecture, Japan.
AB - This was a descriptive study of elderly persons with dementia who were found dead
after becoming lost in the community. Nineteen forensic autopsy cases were
performed at Kochi Medical School, Japan. The mean age of the patients (9 males
and 10 females) was 82.1 +/- 6.6 years. Causes of death were drowning (n = 8),
trauma (n = 5), hypothermia (n = 2), and debilitation possibly due to fatigue (n
= 1) or were unknown (n = 3). Thirteen (68%) individuals had been reported
missing, most at least 6 hours after they had left. They moved on foot (n = 14),
by car (n = 3), or by bicycle (n = 2). Distances from residences to spots of
death ranged from 20 to 5800 m for 11 patients on foot. In 8 cases, it was less
than 500 m. The study has potential implications for enabling their early
discovery and protection.
PMID- 25115168
TI - Peri-procedural interrupted oral anticoagulation for atrial fibrillation
ablation: comparison of aspirin, warfarin, dabigatran, and rivaroxaban.
AB - AIMS: Atrial fibrillation ablation requires peri-procedural oral anticoagulation
(OAC) to prevent thromboembolic events. There are several options for OAC. We
evaluate peri-procedural AF ablation complications using a variety of peri
procedural OACs. METHODS AND RESULTS: We examined peri-procedural OAC and groin,
bleeding, and thromboembolic complications for 2334 consecutive AF ablations
using open irrigated-tip radiofrequency (RF) catheters. Pre-ablation OAC was
warfarin in 1113 (47.7%), dabigatran 426 (18.3%), rivaroxaban 187 (8.0%), aspirin
472 (20.2%), and none 136 (5.8%). Oral anticoagulation was always interrupted and
intraprocedural anticoagulation was unfractionated heparin (activated clotting
time, ACT = 237 +/- 26 s). Pre- and post-OAC drugs were the same for 1591 (68.2%)
and were different for 743 (31.8%). Following ablation, 693 (29.7%) were treated
with dabigatran and 291 (12.5%) were treated with rivaroxaban. There were no
problems changing from one OAC pre-ablation to another post-ablation.
Complications included 12 (0.51%) pericardial tamponades [no differences for
dabigatran (P = 0.457) or rivaroxaban (P = 0.163) compared with warfarin], 12
(0.51%) groin complications [no differences for rivaroxaban (P = 0.709) and fewer
for dabigatran (P = 0.041) compared with warfarin]. Only 5 of 2334 (0.21%)
required blood transfusions. There were two strokes (0.086%) and no transient
ischaemic attacks (TIAs) in the first 48 h post-ablation. Three additional
strokes (0.13%), and two TIAs (0.086%) occurred from 48 h to 30 days. Only one
stroke had a residual deficit. Compared with warfarin, the neurologic event rate
was not different for dabigatran (P = 0.684) or rivaroxaban (P = 0.612).
CONCLUSION: Using interrupted OAC, low target intraprocedural ACT, and irrigated
tip RF, the rate of peri-procedural groin, haemorrhagic, and thromboembolic
complications was extremely low. There were only minimal differences between
OACs. Low-risk patients may remain on aspirin/no OAC pre-ablation. There are no
problems changing from one OAC pre-ablation to another post-ablation.
PMID- 25115171
TI - Interaction of anionic phenylene ethynylene polymers with lipids: from membrane
embedding to liposome fusion.
AB - Here we report spectroscopic studies on the interaction of negatively charged,
amphiphilic polyphenylene ethynylene (PPE) polymers with liposomes prepared
either from negative, positive or zwitterionic lipids. Emission spectra of PPEs
of 7 and 49 average repeat units bearing carboxylate terminated side chains
showed that the polymer embeds within positively charged lipids where it exists
as free chains. No interaction was observed between PPEs and negatively charged
lipids. Here the polymer remained aggregated giving rise to broad emission
spectra characteristic of the aggregate species. In zwitterionic lipids, we
observed that the majority of the polymer remained aggregated yet a small
fraction readily embedded within the membrane. Titration experiments revealed
that saturation of zwitterionic lipids with polymer typically occurred at a
polymer repeat unit to lipid mole ratio close to 0.05. No further membrane
embedding was observed above that point. For liposomes prepared from positively
charged lipids, saturation was observed at a PPE repeat unit to lipid mole ratio
of ~0.1 and liposome precipitation was observed above this point. FRET studies
showed that precipitation was preceded by lipid mixing and liposome fusion
induced by the PPEs. This behavior was prominent for the longer polymer and
negligible for the shorter polymer at a repeat unit to lipid mole ratio of 0.05.
We postulate that fusion is the consequence of membrane destabilization whereby
the longer polymer gives rise to more extensive membrane deformation than the
shorter polymer.
PMID- 25115173
TI - Anesthesia-induced epilepsy: causes and treatment.
AB - Epilepsy is a type of chronic brain disease that results from an abnormally high
synchronization of neuronal discharge. The typical clinical features of epilepsy
are paroxysms and transient and stereotyped brain dysfunction. Many cases of
epileptic seizures occurring during anesthesia have been reportedx. Recently,
risk assessment of epileptic seizures during surgery and anesthesia has gained
increasing attention. In this review, we systematically summarize the influence
of anesthesia on epileptic seizures; the types, durations and frequencies of
seizures related to anesthesia; and the epidemiology, prevention, treatment and
prognosis of epilepsy. We also explore the possible mechanism of epilepsy and
provide guidance for anesthesia during surgeries.
PMID- 25115172
TI - Reassessing the approach to informed consent: the case of unrelated hematopoietic
stem cell transplantation in adult thalassemia patients.
AB - INTRODUCTION: The informed consent process is the legal embodiment of the
fundamental right of the individual to make decisions affecting his or her
health., and the patient's permission is a crucial form of respect of freedom and
dignity, it becomes extremely important to enhance the patient's understanding
and recall of the information given by the physician. This statement acquires
additional weight when the medical treatment proposed can potentially be
detrimental or even fatal. This is the case of thalassemia patients pertaining to
class 3 of the Pesaro classification where Allogenic hematopoietic stem cell
transplantation (HSCT) remains the only potentially curative treatment.
Unfortunately, this kind of intervention is burdened by an elevated
transplantation-related mortality risk (TRM: all deaths considered related to
transplantation), equal to 30% according to published reports. In thalassemia,
the role of the patient in the informed consent process leading up to HSCT has
not been fully investigated. This study investigated the hypothesis that
information provided by physicians in the medical scenario of HSCT is not fully
understood by patients and that misunderstanding and communication biases may
affect the clinical decision-making process. METHODS: A questionnaire was either
mailed or given personally to 25 patients. A second questionnaire was
administered to the 12 physicians attending the patients enrolled in this study.
Descriptive statistics were used to evaluate the communication factors. RESULTS:
The results pointed out the difference between the risks communicated by
physicians and the risks perceived by patients. Besides the study highlighted the
mortality risk considered to be acceptable by patients and that considered to be
acceptable by physicians. CONCLUSIONS: Several solutions have been suggested to
reduce the gap between communicated and perceived data. A multi-disciplinary
approach may possibly help to attenuate some aspects of communication bias.
Several tools have also been proposed to fill or to attenuate the gap between
communicated and perceived data. But the most important tool is the ability of
the physician to comprehend the right place of conscious consent in the
relationship with the patient.
PMID- 25115175
TI - NBOMe designer drug exposures reported to Texas poison centers.
AB - Use of 2-methoxybenzyl analogues of 2C-X phenethylamines (NBOMe) is increasing in
the United States. Twenty-five NBOMe exposures reported to Texas poison centers
during 2012-2013 were identified; 76% involved 25I-NBOMe, 12% involved 25C-NBOMe,
and 12% involved an unknown NBOMe. Eighty-eight percent of the patients were men;
mean age was 17 years (range, 14-25 years). The exposure route was 72% from
ingestion alone, 12% from inhalation alone, 4% from ingestion and inhalation, and
12% from an unknown route. The most common clinical effects were tachycardia
(52%), agitation (48%), hallucinations (32%), hypertension (32%), confusion
(24%), and mydriasis (20%). Two patients died.
PMID- 25115174
TI - Limited role for ASC and NLRP3 during in vivo Salmonella Typhimurium infection.
AB - BACKGROUND: The inflammasome is an intracellular protein complex triggered by
exposure to intracellular pathogens, its components or other endogenous proteins.
It leads to the activation of and subsequent release of proinflammatory cytokines
such as IL-1beta and IL-18. S. Typhimurium is a Gram-negative intracellular
bacterium, which is known to trigger inflammasome assembly via recognition by the
cytosolic receptors, NLRP3 and NLRC4 (which act via the adaptor protein, ASC) to
induce cell death and cytokine release. We sought to characterize the role of ASC
and NLRP3 in two different murine models (typhoid and colitis) of systemic
Salmonella infection. RESULTS: Release of the inflammasome cytokine IL-18 was
hampered in Asc-/- but not Nlrp3-/- mice (background C57BL/6) during S.
Typhimurium infection. Unexpectedly, neither ASC nor NLRP3 played a significant
role in host defense against S. Typhimurium infection, as reflected by equal
bacterial counts in WT, Asc-/- and Nlrp3-/- mice at all time points, in both the
typhoid and colitis models. Proinflammatory cytokine levels (TNF-alpha, IL-6) and
the extent of hepatic and splenic pathology did not differ between groups in the
typhoid model. In the colitis model small differences were seen with regard to
splenic and hepatic inflammation, although this was IL-18 independent.
CONCLUSIONS: IL-18 release was reduced in Asc-/- but not Nlrp3-/- mice during S.
Typhimurium infection. Despite this reduction, bacterial counts, cytokine levels
and histological inflammation did not differ between wild-type and knockout mice
in either model. Our results reveal a limited role for ASC and NLRP3 during in
vivo S. Typhimurium infection despite its role in cytokine maturation.
PMID- 25115176
TI - When early life growth restriction in rats is followed by attenuated postnatal
growth: effects on cardiac function in adulthood.
AB - PURPOSE: Epidemiological and experimental studies demonstrate that intrauterine
growth restriction (IUGR) followed by accelerated postnatal growth leads to
increased risk of developing cardiac disease in adulthood. The aim of this study
was to examine the effect of early life growth restriction on cardiac structure
and function in young adult rats. METHODS: IUGR was induced in Wistar Kyoto dams
through administration of a low protein diet (LPD; 8.7% casein) during pregnancy
and lactation; controls received a normal protein diet (NPD; 20% casein). Cardiac
function and structure were assessed in female NPD (n = 7) and LPD (n = 7)
offspring at 18 weeks of age by echocardiography and pressure-volume techniques,
and systolic blood pressure by tail-cuff sphygmomanometry. RESULTS: LPD offspring
remained significantly smaller throughout life compared to controls. There were
no differences in the levels of systolic blood pressure, left ventricular cardiac
dimensions, heart rate, ejection fraction and fractional shortening of the
cardiac muscle between the investigated groups. Aortic peak systolic velocity was
significantly reduced in the LPD group (P = 0.02). CONCLUSION: Our findings
support the idea that the programming of adult cardiovascular disease can be
prevented or delayed in IUGR offspring when postnatal growth trajectory resembles
that of in utero.
PMID- 25115178
TI - The ADO index as a predictor of two-year mortality in general practice-based
chronic obstructive pulmonary disease cohorts.
AB - BACKGROUND: Existing prediction models for mortality in chronic obstructive
pulmonary disease (COPD) patients have not yet been validated in primary care,
which is where the majority of patients receive care. OBJECTIVES: Our aim was to
validate the ADO (age, dyspnoea, airflow obstruction) index as a predictor of 2
year mortality in 2 general practice-based COPD cohorts. METHODS: Six hundred and
forty-six patients with COPD with GOLD (Global Initiative for Chronic Obstructive
Lung Disease) stages I-IV were enrolled by their general practitioners and
followed for 2 years. The ADO regression equation was used to predict a 2-year
risk of all-cause mortality in each patient and this risk was compared with the
observed 2-year mortality. Discrimination and calibration were assessed as well
as the strength of association between the 15-point ADO score and the observed 2
year all-cause mortality. RESULTS: Fifty-two (8.1%) patients died during the 2
year follow-up period. Discrimination with the ADO index was excellent with an
area under the curve of 0.78 [95% confidence interval (CI) 0.71-0.84]. Overall,
the predicted and observed risks matched well and visual inspection revealed no
important differences between them across 10 risk classes (p = 0.68). The odds
ratio for death per point increase according to the ADO index was 1.50 (95% CI
1.31-1.71). CONCLUSIONS: The ADO index showed excellent prediction properties in
an out-of-population validation carried out in COPD patients from primary care
settings.
PMID- 25115179
TI - Probing anisotropic surface properties and interaction forces of chrysotile rods
by atomic force microscopy and rheology.
AB - Understanding the surface properties and interactions of nonspherical particles
is of both fundamental and practical importance in the rheology of complex fluids
in various engineering applications. In this work, natural chrysotile, a
phyllosilicate composed of 1:1 stacked silica and brucite layers which coil into
cylindrical structure, was chosen as a model rod-shaped particle. The
interactions of chrysotile brucite-like basal or bilayered edge planes and a
silicon nitride tip were measured using an atomic force microscope (AFM). The
force-distance profiles were fitted using the classical Derjaguin-Landau-Verwey
Overbeek (DLVO) theory, which demonstrates anisotropic and pH-dependent surface
charge properties of brucite-like basal plane and bilayered edge surface. The
points of zero charge (PZC) of the basal and edge planes were estimated to be
around pH 10-11 and 6-7, respectively. Rheology measurements of 7 vol %
chrysotile (with an aspect ratio of 14.5) in 10 mM NaCl solution showed pH
dependent yield stress with a local maximum around pH 7-9, which falls between
the two PZC values of the edge and basal planes of the rod particles. On the
basis of the surface potentials of the edge and basal planes obtained from AFM
measurements, theoretical analysis of the surface interactions of edge-edge,
basal-edge, and basal-basal planes of the chrysotile rods suggests the yield
stress maximum observed could be mainly attributed to the basal-edge attractions.
Our results indicate that the anisotropic surface properties (e.g., charges) of
chrysotile rods play an important role in the particle-particle interaction and
rheological behavior, which also provides insight into the basic understanding of
the colloidal interactions and rheology of nonspherical particles.
PMID- 25115177
TI - Short- and long-term effects of a maternal low-energy diet ad libitum during
gestation and/or lactation on physiological parameters of mothers and male
offspring.
AB - PURPOSE: To investigate the short- and long-term effects of a maternal low-energy
diet ad libitum during gestation and/or lactation on mothers and their offspring.
METHODS: Male Wistar rats were divided into four groups according to their
mother's diet: control [C (19.0% protein, 63.0% carbohydrates and 18.0% lipids,
total energetic value (TEV) = 3.5 kcal/g) during gestation and lactation], low
energy diet (18% protein, 64% carbohydrates and 18% lipids, TEV = 2.3 kcal/g)
during gestation (LE-G), low-energy diet during lactation (LE-L) and low-energy
diet during gestation and lactation (LE-GL). Additional crude fibers (10% more
purified cellulose and soluble fiber) and water (approximately 30% greater
moisture) were added to the LE diet to decrease TEV. Mother's body weight, food
intake and energy intake were recorded daily. Birth weight, growth rate, ontogeny
of reflexes, physical features and biochemical parameters at 150 days old were
evaluated in male offspring. RESULTS: Maternal low-energy diet during gestation
did not affect maternal body weight and food intake. Physical features did not
change but reflex ontogeny was delayed in pups from LE dams. LE-G offspring
recovered body size (weight and length) while animals LE-L and LE-GL recovered
their body length but remained lighter until adult life even with no change of
food intake. LE-G and LE-GL showed lower plasma triglycerides and very-low
density-lipoprotein cholesterol (VLDL). LE-L offspring showed
hypertriglyceridemia, high VLDL-c and reduced glycaemia. CONCLUSION: Maternal low
energy diet shows discernible short- and long-term effects on offspring, and this
is dependent on the time of perinatal period.
PMID- 25115180
TI - Light and chemical control of neuronal circuits: possible applications in
neurotherapy.
AB - Millions of people worldwide suffer from diseases that result from a failure of
central pathways to regulate behavioral and physiological processes. Advances in
genetics and pharmacology have already allowed us to appreciate that rather than
this dysregulation being systemic throughout the brain, it is usually rooted in
specific subsets of dysfunctional cells within discrete neurological circuits.
This article discusses the advent of opto- and chemogenetic tools and how they
are providing the means to dissect these circuits with a degree of temporal and
spatial sensitivity not previously possible. We also highlight the potential
applications for treating disease and the key developments likely to have the
greatest impact over the next 5 years.
PMID- 25115181
TI - Down-regulation of BTG1 by miR-454-3p enhances cellular radiosensitivity in renal
carcinoma cells.
AB - BACKGROUND: B cell translocation gene 1 (BTG1) has long been recognized as a
tumor suppressor gene. Recent reports demonstrated that BTG1 plays an important
role in progression of cell cycle and is involved in cellular response to
stressors. However, the microRNAs mediated regulatory mechanism of BTG1
expression has not been reported so far. MicroRNAs can effectively influence
tumor radiosensitivity by preventing cell cycle progression, resulting in
enhancement of the cytotoxicity of radiotherapy efficacy. This study aimed to
demonstrating the effects of microRNAs on the BTG1 expression and cellular
radiosensitivity. METHODS: The human renal carcinoma 786-O cells were treated
with 5 Gy of X-rays. Expressions of BTG1 gene and miR-454-3p, which was predicted
to target BTG1 by software algorithm, were analyzed by quantitative polymerase
chain reaction. Protein expressions were assessed by Western blot. Luciferase
assays were used to quantify the interaction between BTG1 3'-untranslated region
(3'-UTR) and miR-454-3p. The radiosensitivity was quantified by the assay of cell
viability, colony formation and caspase-3 activity. RESULTS: The expression of
the BTG1 gene in 786-O cells was significantly elevated after treatments with X
ray irradiation, DMSO, or serum starvation. The up-regulation of BTG1 after
irradiation reduced cellular radiosensitivity as demonstrated by the enhanced
cell viability and colony formation, as well as the repressed caspase-3 activity.
In comparison, knock down of BTG1 by siRNA led to significantly enhanced cellular
radiosensitivity. It was found that miR-454-3p can regulate the expression of
BTG1 through a direct interaction with the 3'-UTR of BTG1 mRNA. Decreasing of its
expression level correlates well with BTG1 up-regulation during X-ray
irradiation. Particularly, we observed that over-expression of miR-454-3p by
transfection inhibited the BTG1 expression and enhanced the radiosensitivity. In
addition, cell cycle analysis showed that over-expression of miR-454-3p shifted
the cell cycle arrest from G2/M phase to S phase. CONCLUSIONS: Our results
indicate that BTG1 is a direct target of miR-454-3p. Down-regulation of BTG1 by
miR-454-3p renders tumor cells sensitive to radiation. These results may shed
light on the potential application in tumor radiotherapy.
PMID- 25115183
TI - Getting higher: co-occurring drug use among marijuana-using emerging adults.
AB - The most widely used illicit drug in the United States continues to be marijuana,
and its use among emerging adults continues to increase. Marijuana use can result
in a range of negative consequences and has been associated with other drug use
in adolescents and emerging adults. This study examined the relationship between
marijuana use frequency and the use of six other drug classes (opiates, cocaine,
stimulants, hallucinogens, inhalants, and sleep medications) among emerging
adults. A cross-sectional interview design was used with a community sample of
1,075 emerging adults in the northeastern United States. Using logistic
regression analysis controlling for age, ethnicity, gender, and frequency of
binge alcohol, daily marijuana use was found to be associated with a significant
increase in the expected odds of opiate, cocaine, stimulant, hallucinogen,
inhalant, and tobacco use. The findings identify a subgroup of emerging adult
marijuana users-those who use daily-that may be vulnerable to additional negative
consequences associated with polysubstance use.
PMID- 25115182
TI - Alternative splicing in osteoclasts and Paget's disease of bone.
AB - BACKGROUND: Mutations in the SQSTM1/p62 gene have been reported in Paget's
disease of bone (PDB), but they are not sufficient to induce the pagetic
osteoclast (OC) phenotype. We hypothesized that specific RNA isoforms of OC
related genes may contribute to the overactivity of pagetic OCs, along with other
genetic predisposing factors. METHODS: Alternative splicing (AS) events were
studied using a PCR-based screening strategy in OC cultures from 29 patients with
PDB and 26 healthy donors (HD), all genotyped for the p62P392L mutation. Primer
pairs targeting 5223 characterized AS events were used to analyze relative
isoform ratios on pooled cDNA from samples of the four groups (PDB, PDBP392L, HD,
HDP392L). Of the 1056 active AS events detected in the screening analysis, 192
were re-analyzed on non-amplified cDNA from each subject of the whole cohort.
RESULTS: This analysis led to the identification of six AS events significantly
associated with PDB, but none with p62P392L. The corresponding genes included
LGALS8, RHOT1, CASC4, USP4, TBC1D25, and PIDD. In addition, RHOT1 and LGALS8
genes were upregulated in pagetic OCs, as were CASC4 and RHOT1 genes in the
presence of p62P392L. Finally, we showed that the proteins encoded by LGALS8,
RHOT1, USP4, TBC1D25, and PIDD were expressed in human OCs. CONCLUSION: This
study allowed the identification of hitherto unknown players in OC biology, and
our findings of a differential AS in pagetic OCs may generate new concepts in the
pathogenesis of PDB.
PMID- 25115185
TI - Spreading and arrest of a molten liquid on cold substrates.
AB - Understanding the spreading and solidification of liquids on cold solid surfaces
is a problem of fundamental importance and general utility. The physics of
nonisothermal spreading followed by phase change is still a mystery. The present
work focuses on the dynamics and thermal characteristics of liquid drop spreading
and their subsequent arrest due to freezing. The spreading of liquid is recorded,
and the evolution of the liquid spreading diameter and liquid-solid contact angle
is measured from the recordings of a high-speed digital camera. After the
initiation of solidification, the liquid drops are pinned to the substrate,
showing fixed footprints and contact angles. A physical hypothesis using scaling
is provided to explain the relationship between the arrested base diameter (D*)
and arrested contact angle (theta*) with respect to the Stefan number (Ste). The
experimental observations of solidified drops on cold substrates corroborate the
derived physical theory.
PMID- 25115187
TI - Identifying correlates of success and failure of native freshwater fish
reintroductions.
AB - Reintroduction of imperiled native freshwater fish is becoming an increasingly
important conservation tool amidst persistent anthropogenic pressures and new
threats related to climate change. We summarized trends in native fish
reintroductions in the current literature, identified predictors of
reintroduction outcome, and devised recommendations for managers attempting
future native fish reintroductions. We constructed random forest classifications
using data from 260 published case studies of native fish reintroductions to
estimate the effectiveness of variables in predicting reintroduction outcome. The
outcome of each case was assigned as a success or failure on the basis of the
author's perception of the outcome and on whether or not survival, spawning, or
recruitment were documented during post-reintroduction monitoring. Inadequately
addressing the initial cause of decline was the best predictor of reintroduction
failure. Variables associated with habitat (e.g., water quality, prey
availability) were also good predictors of reintroduction outcomes, followed by
variables associated with stocking (e.g., genetic diversity of stock source,
duration of stocking event). Consideration of these variables by managers during
the planning process may increase the likelihood for successful outcomes in
future reintroduction attempts of native freshwater fish.
PMID- 25115184
TI - S-nitrosation of mitochondrial connexin 43 regulates mitochondrial function.
AB - S-nitrosation (SNO) of connexin 43 (Cx43)-formed channels modifies dye uptake in
astrocytes and gap junctional communication in endothelial cells. Apart from
forming channels at the plasma membrane of several cell types, Cx43 is also
located at the inner membrane of myocardial subsarcolemmal mitochondria (SSM),
but not in interfibrillar mitochondria (IFM). The absence or pharmacological
blockade of mitochondrial Cx43 (mtCx43) reduces dye and potassium uptake. Lack of
mtCx43 is associated with loss of endogenous cardioprotection by ischemic
preconditioning (IPC), which is mediated by formation of reactive oxygen species
(ROS). Whether or not mitochondrial Lucifer Yellow (LY), ion uptake, or ROS
generation are affected by SNO of mtCx43 and whether or not cardioprotective
interventions affect SNO of mtCx43 remains unknown. In SSM from rat hearts,
application of NO donors (48 nmol to 1 mmol) increased LY uptake (0.5 mmol SNAP
38.4 +/- 7.1 %, p < 0.05; 1 mmol GSNO 28.1 +/- 7.4 %, p < 0.05) and the refilling
rate of potassium (SNAP 227.9 +/- 30.1 %, p < 0.05; GSNO 122.6 +/- 28.1 %, p <
0.05). These effects were absent following blockade of Cx43 hemichannels by
carbenoxolone as well as in IFM lacking Cx43. Unlike potassium, the sodium
permeability was not affected by application of NO. Furthermore, mitochondrial
ROS formation was increased following NO application compared to control SSM (0.5
mmol SNAP 22.9 +/- 1.8 %, p < 0.05; 1 mmol GSNO 40.6 +/- 7.1 %, p < 0.05), but
decreased in NO treated IFM compared to control (0.5 mmol SNAP 14.4 +/- 4 %, p <
0.05; 1 mmol GSNO 13.8 +/- 4 %, p < 0.05). NO donor administration to isolated
SSM increased SNO of mtCx43 by 109.2 +/- 15.8 %. Nitrite application (48 nmol) to
mice was also associated with elevated SNO of mtCx43 by 59.3 +/- 18.2 % (p <
0.05). IPC by four cycles of 5 min of ischemia and 5 min of reperfusion increased
SNO of mtCx43 by 41.6 +/- 1.7 % (p < 0.05) when compared to control perfused rat
hearts. These data suggest that SNO of mtCx43 increases mitochondrial
permeability, especially for potassium and leads to increased ROS formation. The
increased amount of SNO mtCx43 by IPC or nitrite administration may link NO and
Cx43 in the signal transduction cascade of cardioprotective interventions.
PMID- 25115186
TI - Motivationally significant self-control: enhanced action withholding involves the
right inferior frontal junction.
AB - In everyday life, people use self-control to withhold actions. This ability is
particularly important when the consequences of action withholding have an impact
on the individual's well-being. Despite its importance, it is unclear as to how
the neural nodes implicated in action withholding contribute to this real-world
type of self-control. By modifying an action withholding paradigm, the go/no-go
task, we examined how the brain exerts self-control during a scenario in which
the implications of withholding an action are meaningful and motivationally
significant. A successfully withheld response contributed to long-term monetary
rewards, whereas failure to withhold a response incurred an immediate monetary
punishment. Compared with neutral action withholding, participants significantly
improved their performance when these contingencies were applied. Crucially,
although the right IFG and pre-SMA were found to promote overall action
withholding, the enhancement in behavioral performance relative to a neutral
condition was only reflected by a physiological change in a region encompassing
the right inferior frontal junction and precentral gyrus. We speculate that the
ability to flexibly modulate attention to goal-relevant stimuli is crucial to
enhanced, motivationally driven action withholding and that this ability is
subserved by the right inferior frontal junction. These findings suggest that
control-modulating factors, rather than action withholding processes per se, can
be critical to improving motivationally significant action withholding outcomes.
PMID- 25115188
TI - Accuracy of cytotechnologist evaluation of specimen adequacy and screening
interpretation of malignancy in fine-needle aspiration of the liver.
AB - OBJECTIVE: To evaluate the performance of cytotechnologists in assessing the
adequacy and accuracy of the preliminary diagnosis for fine-needle aspirates of
the liver. STUDY DESIGN: We retrospectively analyzed 10 years of data and found
589 cases of ultrasound-guided fine-needle aspiration (FNA) of the liver with on
site evaluation of adequacy (OSEA). All the OSEA were performed by the
cytopathologist because OSEA of liver FNA is not performed by cytotechnologists
at our institution at present. After OSEA, the material was seen by
cytotechnologists who rendered an adequacy assessment and preliminary diagnosis.
We calculated the adequacy and accuracy statistics and compared the performance
of the cytotechnologists with the OSEA and final interpretation. RESULTS: There
was no statistically significant difference in adequacy downgrade rate for
cytotechnologist versus cytopathologist assessment during the study period (5 vs.
3%, p = 0.06). A total agreement of 88% was noted in overall diagnosis with 97%
agreement in malignant cases. CONCLUSION: Cytotechnologists assess the adequacy
of liver FNA accurately and there is therefore potential for them to perform OSEA
for liver FNA.
PMID- 25115191
TI - Towards developing biomarkers for glioblastoma multiforme: a proteomics view.
AB - Glioblastoma multiforme (GBM) is one of the most aggressive and lethal forms of
the primary brain tumors. With predominance of tumor heterogeneity and emergence
of new subtypes, new approaches are needed to develop tissue-based markers for
tumor typing or circulatory markers to serve as blood-based assays. Multi-omics
data integration for GBM tissues would offer new insights on the molecular view
of GBM pathogenesis useful to identify biomarker panels. On the other hand,
mapping differentially expressed tissue proteins for their secretory potential
through bioinformatics analysis or analysis of the tumor cell secretome or tumor
exosomes would enhance our understanding of the tumor microenvironment and
prospects for targeting circulatory biomarkers. In this review, the authors first
present potential biomarker candidates for GBM that have been reported and then
focus on plausible pipelines for multi-omic data integration to identify
additional, high-confidence molecular panels for clinical applications in GBM.
PMID- 25115189
TI - The bidirectional tumor--mesenchymal stromal cell interaction promotes the
progression of head and neck cancer.
AB - INTRODUCTION: Mesenchymal stromal cells (MSC) are an integral cellular component
of the tumor microenvironment. Nevertheless, very little is known about MSC
originating from human malignant tissue and modulation of these cells by tumor
derived factors. The aim of this study was to isolate and characterize MSC from
head and neck squamous cell carcinoma (HNSCC) and to investigate their
interaction with tumor cells. METHODS: MSC were isolated from tumor tissues of
HNSCC patients during routine oncological surgery. Immunophenotyping,
immunofluorescence and in vitro differentiation were performed to determine
whether the isolated cells met the consensus criteria for MSC. The cytokine
profile of tumor-derived MSC was determined by enzyme-linked immunosorbent assay
(ELISA). Activation of MSC by tumor-conditioned media was assessed by measuring
cytokine release and expression of CD54. The impact of MSC on tumor growth in
vivo was analyzed in a HNSCC xenograft model. RESULTS: Cells isolated from HNSCC
tissue met the consensus criteria for MSC. Tumor-derived MSC constitutively
produced high amounts of interleukin (IL)-6, IL-8 and stromal cell-derived factor
(SDF)-1alpha. HNSCC-derived factors activated MSC and enhanced secretion of IL-8
and expression of CD54. Furthermore, MSC provided stromal support for human HNSCC
cell lines in vivo and enhanced their growth in a murine xenograft model.
CONCLUSIONS: This is the first study to isolate and characterize MSC from
malignant tissues of patients with HNSCC. We observed cross-talk of stromal cells
and tumor cells resulting in enhanced growth of HNSCC in vivo.
PMID- 25115193
TI - Systematic Review of the Manifestations of Congenital Rubella Syndrome in Infants
and Characterization of Disability-Adjusted Life Years (DALYs).
AB - Congenital rubella syndrome (CRS) continues to cause disability among
unvaccinated populations in countries with no or insufficient rubella vaccine
coverage to prevent transmission. We systematically reviewed the literature on
birth outcomes associated with CRS to estimate the duration, severity, and
frequency of combinations of morbidities. We searched PubMed, the Science
Citation Index, and references from relevant articles for studies in English with
primary data on the frequency of CRS manifestations for >=20 cases and identified
65 studies representing 66 study populations that met our inclusion criteria. We
abstracted available data on CRS cases with one or more hearing, heart, and/or
eye defect following maternal rubella infection during the period of 0-20 weeks
since the last menstrual period. We assessed the quality and weight of the
available evidence using a modified Grading of Recommendations Assessment,
Development and Evaluation (GRADE) approach. Most of the evidence originates from
studies in developed countries of cohorts of infants identified with CRS in the
1960s and 1970s, prior to the development of standardized definitions for CRS and
widespread use of vaccine. We developed estimates of undiscounted disability
adjusted life years (DALYs) lost per CRS case for countries of different income
levels. The estimates ranged from approximately 19 to 39 for high-income
countries assuming optimal treatment and from approximately 29 to 39 DALYs lost
per CRS case in low- and lower- middle-income countries assuming minimal
treatment, with the lower bound based on 2010 general global burden of disease
disability weights and the upper bound based on 1990 age-specific and treatment
specific global burden of disease disability weights. Policymakers and analysts
should appreciate the significant burden of disability caused by CRS as they
evaluate opportunities to manage rubella.
PMID- 25115192
TI - Gene signatures ESC, MYC and ERG-fusion are early markers of a potentially
dangerous subtype of prostate cancer.
AB - BACKGROUND: Good prognostic tools for predicting disease progression in early
stage prostate cancer (PCa) are still missing. Detection of molecular subtypes,
for instance by using microarray gene technology, can give new prognostic
information which can assist personalized treatment planning. The detection of
new subtypes with validation across additional and larger patient cohorts is
important for bringing a potential prognostic tool into the clinic. METHODS: We
used fresh frozen prostatectomy tissue of high molecular quality to further
explore four molecular subtype signatures of PCa based on Gene Set Enrichment
Analysis (GSEA) of 15 selected gene sets published in a previous study. For this
analysis we used a statistical test of dependent correlations to compare
reference signatures to signatures in new normal and PCa samples, and also
explore signatures within and between sample subgroups in the new samples.
RESULTS: An important finding was the consistent signatures observed for samples
from the same patient independent of Gleason score. This proves that the
signatures are robust and can surpass a normally high tumor heterogeneity within
each patient. Our data did not distinguish between four different subtypes of PCa
as previously published, but rather highlighted two groups of samples which could
be related to good and poor prognosis based on survival data from the previous
study.The poor prognosis group highlighted a set of samples characterized by
enrichment of ESC, ERG-fusion and MYC + rich signatures in patients diagnosed
with low Gleason score,. The other group consisted of PCa samples showing good
prognosis as well as normal samples. Accounting for sample composition (the
amount of benign structures such as stroma and epithelial cells in addition to
the cancer component) was important to improve subtype assignments and should
also be considered in future studies. CONCLUSION: Our study validates a previous
molecular subtyping of PCa in a new patient cohort, and identifies a subgroup of
PCa samples highly interesting for detecting high risk PCa at an early stage. The
importance of taking sample tissue composition into account when assigning
subtype is emphasized.
PMID- 25115197
TI - Do palliative care interventions reduce emergency department visits among
patients with cancer at the end of life? A systematic review.
AB - BACKGROUND: Frequent emergency department (ED) visits are an indicator of poor
quality of cancer care. Coordination of care through the use of palliative care
teams may limit aggressive care and improve outcomes for patients with cancer at
the end of life. OBJECTIVES: To systematically review the literature to determine
whether palliative care interventions implemented in the hospital, home, or
outpatient clinic are more effective than usual care in reducing ED visits among
patients with cancer at the end of life. ELIGIBILITY CRITERIA: PubMed, EMBASE,
and CINAHL databases were searched from database inception to May 7, 2014. Only
randomized/non-randomized controlled trials (RCTs) and observational studies
examining the effect of palliative care interventions on ED visits among adult
patients with cancer with advanced disease were considered. DATA EXTRACTION AND
DATA SYNTHESIS: Data were abstracted from the articles that met all the inclusion
criteria. A second reviewer independently abstracted data from 2 articles and
discrepancies were resolved. From 464 abstracts, 2 RCTs, 10 observational
studies, and 1 non-RCT/quasi-experimental study were included. Overall there is
limited evidence to support the use of palliative care interventions to reduce ED
visits, although studies examining effect of hospice care and those conducted
outside of the United States reported a statistically significant reduction in ED
visits. CONCLUSIONS: Evidence regarding whether palliative care interventions
implemented in the hospital, home or outpatient clinic are more effective than
usual care at reducing ED visits is not strongly substantiated based on the
literature reviewed. Improvements in the quality of reporting for studies
examining the effect of palliative care interventions on ED use are needed.
PMID- 25115194
TI - Survival rate of etanercept for psoriasis in real life: a multicentre
observational study.
PMID- 25115195
TI - Bridging the gap: Lessons we have learnt from the merging of psychology and
psychiatry for the optimisation of treatments for emotional disorders.
AB - In recent years the gap between psychological and psychiatric research and
practice has lessened. In turn, greater attention has been paid toward how
psychological and pharmacological treatments interact. Unfortunately, the
majority of research has indicated no additive effect of anxiolytics and
antidepressants when combined with psychological treatments, and in many cases
pharmacological treatments attenuate the effectiveness of psychological
treatments. However, as psychology and psychiatry have come closer together,
research has started to investigate the neural and molecular mechanisms
underlying psychological treatments. Such research has utilised preclinical
models of psychological treatments, such as fear extinction, in both rodents and
humans to determine multiple neural and molecular changes that may be responsible
for the long-term cognitive and behavioural changes that psychological treatments
induce. Currently, researchers are attempting to identify pharmacological agents
that directly augment these neural/molecular changes, and which may be more
effective adjuncts to psychological treatments than traditional anxiolytics and
antidepressants. In this review we describe the research that has led to this new
wave of thinking about combined psychological/pharmacological treatments. We also
argue that an increased emphasis on identifying individual difference factors
that predict the effectiveness of pharmacological adjuncts is critical in
facilitating the translation of this preclinical research into clinical practice.
PMID- 25115198
TI - From crab shells to smart systems: chitosan-alkylethoxy carboxylate complexes.
AB - In this work, self-assembly of alkyl ethylene oxide carboxylates and the
biopolymer chitosan into supramolecular structures with various shapes is
presented. Our investigations were done at pH 4.0, where the chitosan is almost
fully charged and the surfactants are partially deprotonated. By changing the
alkyl chain length and the number of ethylenoxide units very different water
soluble complexes can be obtained, ranging from globular micelles incorporated in
a chitosan network to formation of ordered multiwalled vesicles. The structural
characteristics of these complexes can be finely controlled by the mixing ratio
of chitosan and surfactant, i.e., simply by the solutions composition. For
instance, the vesicle wall thickness can be varied between 5 and 50 nm just by
varying the mixing ratio. Accordingly, we expect this system to be an outstanding
carrier for hydrophilic compounds with tunable release time option. Moreover, an
easy route for preparation of chitosan-based complexes in the solid state with
controlled mesoscopic order is presented. This work opens the way to prepare
biofriendly materials on the basis of chitosan and mild anionic surfactants which
are rather versatile with respect to their structure and properties, allowing for
preparation of complexes with highly variable structures in both aqueous and
solid phase. Formation of such different structures can be exploited for
preparation of carriers, which are able to transport hydrophilic as well as
hydrophobic molecules. Furthermore, as chitosan is well known to exhibit
antibacterial and anti-inflammatory properties, different applications of these
complexes can be indicated, i.e., as drug delivery systems or as coatings for
medical implants.
PMID- 25115199
TI - Psychosocial correlates of adolescent cannabis use: data from the Italian
subsample of the second International Self-Reported Delinquency study.
AB - To provide a comprehensive picture of the whole spectrum of psychosocial factors
potentially associated with adolescent cannabis use, bivariate and multivariate
analyses were used to assess a variety of social, demographic, psychological, and
behavioral correlates of last-month cannabis use and age of first use among 6,838
students. Results showed that only family problems, alcohol and/or other drug
use/misuse, deviant behavior, and victimization were independently associated
with either recent cannabis use or early onset of cannabis use when multiple,
interacting factors were considered. Certain family and behavioral factors might
be more important than other psychosocial correlates of adolescent cannabis use.
PMID- 25115200
TI - Associations between follow-up screening after gestational diabetes and early
detection of diabetes--a register based study.
AB - BACKGROUND: Women whose pregnancy was complicated by gestational diabetes have a
7-fold higher risk of developing diabetes, primarily type 2. Early detection can
prevent or delay the onset of late complications, for which follow-up screening
is important. This study investigated the extent of participation in follow-up
screening and the possible consequences of nonattendance in the Region of North
Jutland, Denmark. METHOD: In Danish national registers covering the years 1994
2011 we identified 2171 birthing women whose pregnancy was complicated by first
time gestational diabetes. Control visits to general practitioners and
biochemical departments after giving birth were charted. Following national
guidelines we defined four intervals for assessment of participation in follow-up
screening. Diagnosis of diabetes or treatment with glucose-lowering agents after
giving birth were also identified. Participation in follow-up screening and risk
of diabetes was calculated. Time to obtaining diagnosis of diabetes or initiating
treatment was analysed by Cox regression models. All models were adjusted for
age, ethnicity and income. RESULTS: High attendance was found during the first
control interval, after which attendance decreased with time after giving birth
for both controls at general practitioners and biochemical departments. All
differences in proportions were statistically significant. Women attending
controls at general practitioners had a significantly higher risk of diabetes
diagnosis and treatment after gestational diabetes than women not attending. The
results for women attending testing at biochemical departments also showed an
increased risk of initiation of treatment. Women attending at least one general
practitioners control had a significantly higher risk of early diabetes diagnosis
or treatment. Time to initiation of treatment was significantly higher for
testing at biochemical departments. Women with high incomes had a significantly
lower risk of diabetes diagnosis or initiation of treatment compared to low
income women. CONCLUSION: Participation in follow-up screening after gestational
diabetes is low in the North Denmark Region. Follow-up screening ensures early
detection of diabetes and initiation of treatment. Our results emphasize the
importance of development of interventions to improve early detection and
prevention of diabetes after gestational diabetes.
PMID- 25115201
TI - The p-EVES study design and methodology: a randomised controlled trial to compare
portable electronic vision enhancement systems (p-EVES) to optical magnifiers for
near vision activities in visual impairment.
AB - PURPOSE: To describe the study design and methodology for the p-EVES study, a
trial designed to determine the effectiveness, cost-effectiveness and
acceptability of portable Electronic Vision Enhancement System (p-EVES) devices
and conventional optical low vision aids (LVAs) for near tasks in people with low
vision. METHODS: The p-EVES study is a prospective two-arm randomised cross-over
trial to test the hypothesis that, in comparison to optical LVAs, p-EVES can be:
used for longer duration; used for a wider range of tasks than a single optical
LVA and/or enable users to do tasks that they were not able to do with optical
LVAs; allow faster performance of instrumental activities of daily living; and
allow faster reading. A total of 100 adult participants with visual impairment
are currently being recruited from Manchester Royal Eye Hospital and randomised
into either Group 1 (receiving the two interventions A and B in the order AB), or
Group 2 (receiving the two interventions in the order BA). Intervention A is a 2
month period with conventional optical LVAs and a p-EVES device, and intervention
B is a 2-month period with conventional optical LVAs only. RESULTS: The study
adopts a mixed methods approach encompassing a broad range of outcome measures.
The results will be obtained from the following primary outcome measures:
Manchester Low Vision Questionnaire, capturing device 'usage' data (which devices
are used, number of times, for what purposes, and for how long) and the MNRead
test, measuring threshold print size, critical print size, and acuity reserve in
addition to reading speed at high (~90%) contrast. Results will also be obtained
from a series of secondary outcome measures which include: assessment of timed
instrumental activities of daily living and a 'near vision' visual functioning
questionnaire. A companion qualitative study will permit comparison of results on
how, where, and under what circumstances, p-EVES devices and LVAs are used in
daily life. A health economic evaluation will provide results on: the incremental
cost-effectiveness of p-EVES compared to optical magnifiers; cost-effectiveness;
and cost-utility. CONCLUSIONS: The evidence base in low vision rehabilitation is
modest and further high quality clinical trials are required to inform decisions
on healthcare provision. The p-EVES study findings are anticipated to contribute
to this broader evidence requirement, with the methodological issues evident here
being relevant to other trials within the field.
PMID- 25115203
TI - Porokeratoses: an update of clinical, aetiopathogenic and therapeutic features.
AB - Porokeratoses represent a group of uncommon, acquired or hereditary dermatoses,
due to a keratinization disorder whose origin is still unclear; they could be due
to the expansion of a clone of abnormal epidermal keratinocytes. Several clinical
forms exist, of which the most common is disseminated superficial actinic
porokeratosis; other forms include Mibelli, disseminated superficial, linear,
palmoplantaris punctata and palmaris, plantaris et disseminata. These may coexist
in the same patient or in different members of the same family. Porokeratoses
manifest clinically with annular or linear, well-circumscribed keratotic plaques
and share a common histological hallmark, the cornoid lamella, a vertical stack
of parakeratotic corneocytes within the horny layer resting on a shallow
depression of the underlying epidermis. Porokeratoses may be seen in the setting
of various immunodeficiencies, namely in organ-transplant recipients, in whom the
course of the disease may parallel the degree of immunosuppression. The overall
prognosis of porokeratoses is favourable but is shadowed by the possibility of
malignant transformation of the lesions (usually into squamous cell carcinoma);
this happens in less than 10% of cases but may prove fatal. Although several
surgical or medical (local or systemic) treatments have been tried, none of them
has shown consistent and long-term efficacy.
PMID- 25115204
TI - [Predicting chance of disease: calculation using prediction rules].
AB - A prediction rule is a statistical model that can be used to predict the presence
or absence of a disease based on a limited number of tests or predictive factors.
One of the mathematical methods used to formulate prediction rules is a logistic
regression analysis of patient data. The discriminatory power of a model is
visualizable using box-whisker plots and ROC curves; calibration plots show the
match between the predicted chance and the observed frequency of a disease. These
graphs are used to assess whether a model adequately reproduces reality. On
publication of prediction rules it is important that the regression function is
written out and that the chances of a disease on the basis of diagnostic scores
are displayed in a histogram. For the practical significance of the model, it is
also important to know how often the predicted low, medium or high probabilities
of a disease do actually occur in comparison with the advance chance of
occurrence.
PMID- 25115202
TI - Genetic network identifies novel pathways contributing to atherosclerosis
susceptibility in the innominate artery.
AB - BACKGROUND: Atherosclerosis, the underlying cause of cardiovascular disease,
results from both genetic and environmental factors. METHODS: In the current
study we take a systems-based approach using weighted gene co-expression analysis
to identify a candidate pathway of genes related to atherosclerosis.
Bioinformatic analyses are performed to identify candidate genes and interactions
and several novel genes are characterized using in-vitro studies. RESULTS: We
identify 1 coexpression module associated with innominate artery atherosclerosis
that is also enriched for inflammatory and macrophage gene signatures. Using a
series of bioinformatics analysis, we further prioritize the genes in this
pathway and identify Cd44 as a critical mediator of the atherosclerosis. We
validate our predictions generated by the network analysis using Cd44 knockout
mice. CONCLUSION: These results indicate that alterations in Cd44 expression
mediate inflammation through a complex transcriptional network involving a number
of previously uncharacterized genes.
PMID- 25115205
TI - [Combination of exemestane and everolimus may produce toxic side effects: a new
treatment option for metastatic hormone-sensitive breast cancer].
AB - The combination of exemestane and everolimus is a new treatment option for
metastatic hormone-sensitive breast cancer. This treatment is used after
progression on non-steroidal aromatase inhibitors. The treatment is generally
well tolerated, but sometimes leads to minor or even serious side effects. It is
important to be aware of these side effects and to treat them. We describe two
patients who had to cope with various forms of toxicity: a 73-year-old woman with
aphthous mouth lesions and a 49-year-old woman with pneumonitis. We then discuss
the efficacy of the combination exemestane and everolimus and its positioning in
the treatment of metastatic hormone-sensitive breast cancer. Finally, some common
and some potentially serious side effects will be discussed, along with
recommendations for their management and indications for distinguishing side
effects from disease progression.
PMID- 25115206
TI - [Hyperglycaemia during treatment with everolimus].
AB - BACKGROUND: Everolimus is an orally administered anti-cancer drug that inhibits
the mammalian target of rapamycin (mTOR) signal transduction route. Use of
everolimus may be associated with insulin resistance, manifesting in impaired
glucose tolerance or hyperglycaemia. CASE DESCRIPTION: A 74-year-old female
patient with a locally recurrent breast cancer developed hyperglycaemia, which
started 2 weeks after the initiation of treatment with everolimus 10 mg once
daily. Metformin and insulin were administered to restore normoglycaemia.
CONCLUSION: At the initiation of treatment with an mTOR inhibitor such as
everolimus the treating physician should be aware of the occurrence of
hyperglycaemia. Metformin is then the medicine of first choice.
PMID- 25115207
TI - [Glossopharyngeal neuralgia and syncope].
AB - BACKGROUND: The causes of neuralgia are usually not known, but the condition can
be caused by an underlying condition. CASE DESCRIPTION: A 58-year-old man
presented at the accident and emergency department with a 6-week history of
continuous nagging pain in the region of his right ear, extending to the lower
jaw and the right side of his neck; this worsened in progressive attacks, which
were sometimes followed by non-rotatory dizziness and loss of consciousness. This
clinical picture lead us to suspect glossopharyngeal neuralgia (GPN) because of
the distribution of the pain and the secondary syncope, but the continuous nature
of the pain was atypical and a reason for further investigation. This revealed
metastatic parotid gland carcinoma with compression of the right glossopharyngeal
nerve. Following palliative radiotherapy, the pain improved and there were no
further episodes of loss of consciousness. CONCLUSION: When GPN is suspected and
there is continuous pain, or neurological investigations reveal abnormalities, an
underlying condition should be considered and additional investigations should be
carried out.
PMID- 25115208
TI - [The treatment of drooling in children].
AB - Undesirable drooling in children is an underexposed problem and difficult to
treat, although there are multiple treatment options. A multidisciplinary
approach is preferable for the examination and treatment of patients with
drooling. The injection of botulinum toxin is the most frequently performed
treatment for children who drool, but the effects are temporary. If drooling
persists despite conservative treatment, surgical interventions performed by an
otolaryngologist may be considered and may offer a more definitive solution.
PMID- 25115209
TI - [Treatment of children with intestinal failure: intestinal rehabilitation, home
parenteral nutrition or small intestine transplantation?].
AB - Intestinal failure is characterised by inadequate absorption of food or fluids,
which is caused by insufficient bowel surface area or functioning. Children with
chronic intestinal failure are dependent on parenteral nutrition (PN), which can
be provided at home (HPN). In the Netherlands, HPN for children is coordinated by
special HPN and intestinal failure teams from the Emma Children's Hospital, the
Erasmus MC-Sophia Children's Hospital and the Radboud University Medical Center.
HPN is the treatment of choice for children with chronic intestinal failure.
Small intestine transplantation is only justified if HPN fails because
complications arise; this procedure is carried out at the University Medical
Center in Groningen. In addition to medical complications, HPN has psychosocial
implications both for the children and their parents. Systematic attention to
these can be provided by the 'Quality of Life in Clinical Practice' method, which
also enables collection of data relevant for research purposes.
PMID- 25115211
TI - [Thrombolysis not always necessary in patients with acute pulmonary embolism].
AB - International guidelines suggest that patients presenting with acute pulmonary
embolism should be given routine thrombolysis on top of heparin. There is debate
as to whether patients with acute pulmonary embolism who present in a
haemodynamically stable condition, yet have signs of right ventricular
dysfunction and increased troponin, actually need thrombolytic therapy. The
results of the Pulmonary Embolism Thrombolysis study (PEITHO) show that in this
particular patient group routine thrombolysis led to less haemodynamic
decompensation or collapse, but that this advantage came with significantly
higher incidences of haemorrhagic stroke and major extracranial bleeding. These
results argue against routine thrombolysis in these patients. It is recommended
that anticoagulation with heparin and vitamin K antagonists be given and patients
be carefully monitored in hospital, particularly during the first three days.
PMID- 25115212
TI - [Expensive new drugs for treating cancer: a dilemma].
AB - The number of new cancer patients in the Netherlands is increasing annually:
there were approximately 100,000 new cases in 2010 and there will be more than
120,000 in 2020. The number of systemic therapies available for these patients is
growing rapidly, and spending on anticancer drug doubled within ten years, to EUR
733 m in 2013. During the past few years the amount spent on new targeted drugs
was compensated by the expiration of patents for frequently used cytostatics such
as paclitaxel, docetaxel, gemcitabin, oxaliplatin and irinotecan. Immunotherapy
is now available for patients with metastatic melanoma and the new 'checkpoint
inhibitors' look promising for other cancers, including lung cancer, renal cell
cancer, and bladder cancer. These drugs, as well as the numerous new targeted
agents, are very expensive. The price for 4 cycles of ipilimumab for a patient
with metastatic melanoma is approximately EUR 80,000. A special committee of the
Dutch Cancer Society (KWF) released a report on the increasing costs of
anticancer treatments and gave recommendations concerning how to address this
issue. First of all, cost savings have to be achieved by lowering the price of
the innovative drugs. The search for companion diagnostics should be encouraged,
in order to avoid unnecessary drug administration. And, if these measures are not
sufficient, the government should consider determining a price-ceiling for these
treatments. A differentiation between treatments with curative intention or long
term survival benefits and those which only have marginal effects, would appear
to be logical.
PMID- 25115213
TI - Value of clinical and laboratory inflammation factors in the postoperative period
after laparoscopic urogynecological surgery.
AB - BACKGROUND/AIMS: Leukocytes and C-reactive protein (CRP) levels are often used to
detect infections. The aim of this study was to evaluate the diagnostic and
screening validity of leukocytes and CRP levels as well as body temperature >38
degrees C to predict infections after laparoscopic sacrocolpopexy. METHODS: The
study included 287 patients suffering from genital prolapse higher than POP-Q I.
In addition to the sacrocolpopexy, a laparoscopic supracervical hysterectomy was
performed in cases of preexisting uterus (n = 171). Leukocytes and CRP levels
were analyzed preoperatively and 4 days after surgery. Early and late onset of
infections was documented. RESULTS: Urinary tract infection was identified as the
most frequent early postoperative complication (11.4%). Early wound infections
were found in 2.8% of the patients (8/287). Late onset of infections was found in
1% of patients (3/287). Areas under ROC curves were low for both leukocytes
(0.52, 95% CI: 0.37-0.66) and CRP levels (0.60, 95% CI: 0.44-0.77). CONCLUSION:
Our findings question the benefit of routine determination of leukocytes and CRP
levels 4 days after surgery. The sensitivity and specificity of leukocytes and
CRP levels are probably more significant after normalization of the initial
tissue response (days 8-10).
PMID- 25115214
TI - Foreword. Pertussis vaccines.
PMID- 25115215
TI - Impact of coronary artery disease on left ventricular ejection fraction recovery
following transcatheter aortic valve implantation.
AB - OBJECTIVES: The objective of the present study was to assess if the presence and
severity of CAD is associated with decreased LVEF recovery after TAVI.
BACKGROUND: Coronary artery disease (CAD) and low left ventricular ejection
fraction (LVEF) are common findings in patients undergoing transcatheter aortic
valve implantation (TAVI). The impact of CAD on LVEF recovery after TAVI has not
been specifically evaluated. METHODS: All patients with LVEF<=50% who underwent
TAVI between March 2006 and May 2012 were included in the study. The presence and
severity of coronary artery disease was measured using the Duke Myocardial
Jeopardy Score (DMJS). A DMJS = 0 corresponds to patients without CAD or complete
revascularization and a DMJS > 0 to those with incomplete revascularization. LVEF
recovery was assessed by transthoracic echocardiography, measuring the change in
LVEF from baseline to 3-months post-TAVI. Myocardial viability was evaluated in a
subgroup of patients using cardiac magnetic resonance (CMR) imaging pre-TAVI.
RESULTS: Fifty-six patients were included in the study. Twenty-eight patients
(50%) had a DMJS > 0. At 3 months, patients with incomplete revascularization
(DMJS > 0) demonstrated less LVEF recovery post-TAVI (2.0 +/- 9.2% versus 11.7 +/
8.9% if DMJS = 0; P = 0.001). On multivariate analysis, DMJS and presence of
significant delayed-enhancement were found to be independent predictors of LVEF
recovery. Patients with incomplete revascularization exhibited a worse prognosis
with higher mortality at 30-days (22.2% versus 0% if DMJS = 0; P = 0.010) and 1
year (25.9% versus 3.5% if DMJS = 0; P = 0.019). CONCLUSIONS: The present study
demonstrates an independent association between incomplete revascularization and
decreased LVEF recovery in patients with left ventricular dysfunction undergoing
TAVI for severe aortic stenosis.
PMID- 25115217
TI - Complete penoscrotal transposition: case report and review of the literature.
AB - Penoscrotal transposition is a rare congenital abnormality. We report a case
presenting prenatally with ambiguous genitalia and renal anomaly on obstetric
ultrasound and fetal MRI and discuss the postnatal examination and autopsy
findings. We present a review of the literature, including associated gene
abnormalities.
PMID- 25115216
TI - Nitinol-based nanotubular coatings for the modulation of human vascular cell
function.
AB - In this study, we describe the synthesis of an upright nanotubular coating with
discrete, exposed nanotubes on top of superelastic Nitinol via anodization and
characterization of the surface elemental composition and nickel release rates.
We demonstrate, for the first time, that this coating could improve re
endothelialization by increasing the cell spreading and migration of primary
human aortic endothelial cells on Nitinol. We also show the potential for
reducing neointimal hyperplasia by decreasing the proliferation and expression of
collagen I and MMP-2 in primary human aortic smooth muscle cells (HASMC).
Furthermore, we did not observe the nanotubular surface to induce inflammation
through ICAM-1 expression in HASMC as compared to the flat control. This coating
could be used to improve Nitinol stents by reducing restenosis rates and, given
the extensive use of Nitinol in other implantable devices, act as a generalized
coating strategy for other medical devices.
PMID- 25115218
TI - Barriers to employment of African American professionals in hospice: a
qualitative study with African American social work students.
AB - A major barrier to African American hospice utilization is the lack of African
American hospice professionals. This qualitative study with 10 female African
American social work students in a Midwestern university explored whether the
participants were interested in hospice employment. Results provided information
about reasons for the overall lack of diversity in hospice, reasons for the lack
of African American staff in hospice, reasons for the lack of African American
patients in hospice, and avenues toward knowledge about hospice by African
American professionals. Barriers to African American employment included a lack
of hospice content in social work education, differences between African American
cultural and religious beliefs and hospice philosophy, and that the lack of
African American hospice patients resulted in a lack of desire for employment in
hospice. Strategies for recruiting and retaining African American hospice social
workers are proposed.
PMID- 25115219
TI - Enhancing the interaction between annexin-1 and formyl peptide receptors
regulates microglial activation to protect neurons from ischemia-like injury.
AB - As the immune cells of the brain, microglia are crucial for the maintenance of
brain function. The aims of the present study were to determine whether and how
annexin-1 is able to affect microglial phenotype and migration in the lesion
microenvironment. In the current experiment, we enhanced the interaction between
annexin-1 and formyl peptide receptors in microglia and analyzed the function. We
found that annexin-1 could polarize microglia to a beneficial phenotype and
promote microglial migration to protect neurons from ischemia-like injury, and
the annexin-1-mediated neuroprotective effect was dependent on the release of
glutamate and ATP from the injured neurons.
PMID- 25115220
TI - Is physician awareness of impending death in hospital related to better
communication and medical care?
AB - BACKGROUND: In hospitals, where care is focused on cure and life prolongation,
impending death is often recognized too late. Physician awareness of impending
death is a prerequisite for communication with patients and relatives about dying
in hospital and providing care that adequately addresses patients' needs.
OBJECTIVE: To examine to what extent physicians are aware of the impending death
of their dying patients and if awareness is related with communication and
medical care, with quality of life in the last 3 days and quality of dying.
DESIGN: Retrospective survey among hospital physicians after patient deaths.
SETTING/SUBJECTS: Patients who died between June 2009 and February 2011 at
Erasmus University Medical Center (Rotterdam, The Netherlands). MEASUREMENTS:
Physician self-reported awareness of impending death, communication with patients
and relatives, medical care, quality of life in the last 3 days, and quality of
dying. RESULTS: The response rate was 44% (n=228). Physicians reported that they
had been aware of the impending death in 67% of their dying patients. If they had
been aware, discussing death with patients and relatives was more likely, as well
as changing the treatment goal into comfort care or withholding treatment and
prescribing opioids in the last 3 days of life. When physicians had been aware of
impending death, they rated the quality of dying higher. CONCLUSIONS: In two
thirds of deaths, hospital physicians had been aware of impending death of their
dying patients. Physician awareness was related with more communication and more
appropriate care in the last days of life.
PMID- 25115221
TI - Levels of stigma among community mental health staff in Guangzhou, China.
AB - BACKGROUND: Stigma and discrimination are widely experienced by people with
mental illness, even in healthcare settings. The purposes of this study were to
assess mental health stigma among community mental health staff in Guangzhou,
China and in doing so also to assess the psychometric properties of the Reported
and Intended Behaviour Scale (RIBS) - Chinese version. METHODS: A cross-sectional
survey was undertaken among 214 community mental health staff in Guangzhou from
September to November, 2013. The Mental Health Knowledge Schedule (MAKS) and RIBS
were administered together with the Mental Illness: Clinicians' Attitudes Scale
(MICA) to evaluate staff stigma from the perspective of knowledge, attitudes and
behaviour. RESULTS: The total scores of RIBS, MAKS and MICA were (11.97 +/-
3.41), (16.80 +/- 5.39) and (51.69 +/- 6.94) respectively. Female staff members
were more willing to contact people with mental illness than males (t(212) =
2.85,P = 0.005) and had more knowledge about mental illness (t(212) = -2.28,P =
0.024). The Chinese version of RIBS had good internal consistency (alpha = 0.82),
test-retest reliability (r = 0.68,P < 0.001) and adequate convergent validity, as
indicated by a significant negative correlation with the Chinese version of
MICA(r = -0.43, P < 0.001). CONCLUSIONS: Our results show relatively high levels
of stigma toward people with mental illness among community mental health staff
in Guangzhou, China. There are slightly gender differences in discriminatory
behaviours and stigma related knowledge of mental illness among community mental
health staff, with female staff in general less stigmatising. Accordingly, anti
stigma programmes should be established among healthcare staff. In addition, the
Chinese version of RIBS is a reliable, valid and acceptable measure which can be
used to assess the willingness of participants to contact people with mental
illness in future anti-stigma campaigns.
PMID- 25115223
TI - Tetramine poisoning in China: changes over a decade viewed through the media's
eye.
AB - BACKGROUND: Tetramine, or tetramethylenedisulfotetramine, is an internationally
banned compound that had been used primarily as a rodenticide. Despite its
regulatory status, there are widespread reports of its intentional use in human
poisonings, primarily in China, and often in mass poisonings. Enhanced
governmental regulations were implemented in 2003 to further reduce the
availability of tetramine, though the effects of these regulations, and the
current use of tetramine, remains unknown. METHODS: Reports from the website of
the China News Agency were collected from 2000 to 2012. Details such as the
location, date, and intent of the events were compared before and after the
regulations were implemented. RESULTS: There were a total of 148 events during
the study period (95 from 2000 to 2003, and 53 after 2003). There were a total of
3526 victims, including 225 fatalities. The majority of the events were
homicidal/terroristic in nature. The incidence of events fell after 2006. More
poisoning events occurred in central China, such as Henan and Jiangsu province,
and an increase was noted in April and September. CONCLUSION: Tetramine poisoning
events, as reported in the national Chinese media, fell after the implementation
of strict regulation on tetramine. The causal relationship is not known.
PMID- 25115222
TI - Pelger-Huet anomaly in a cat.
AB - A 14-year-old, spayed female Domestic Shorthair cat was referred to the Purdue
University Veterinary Teaching Hospital (PUVTH) for iodine 131 treatment of
hyperthyroidism. Upon arrival, a biochemistry profile and a CBC were performed.
Approximately 50% of the neutrophils and all the eosinophils observed were
hyposegmented with a mature, condensed chromatin pattern. Nuclei had a band to
"dumbbell" shape, and rarely a round shape, suggesting a Pelger-Huet anomaly or a
pseudo Pelger-Huet. Based on both a negative FeLV and FIV tests, the absence of
any clinical signs to support an inflammatory process, and the persistence of
this granulocytic morphology 6 months after its previous admission to the PUVTH,
a diagnosis of Pelger-Huet anomaly was established in this cat.
PMID- 25115224
TI - Narcotics anonymous: a comparison of military veterans and non-veterans.
AB - Substance use disorder, which is often comorbid with post-traumatic stress
disorder (PTSD), is a problem confronted by many veterans. To determine the
potential utility of Narcotics Anonymous (NA) for veterans, 508 NA attendees were
studied. Veterans (n = 172) were more likely to have been referred by a
professional than were non-veterans (77% vs. 27%, respectively); 70% had been
hospitalized for alcohol or drug problems, and 51% had been treated for non
substance psychological problems. The 70% of veterans who reported at least 1 of
3 service-related stressful experiences were more likely to report PTSD-related
symptoms. NA can serve as a recovery resource for certain veterans with substance
use disorders, with or without PTSD.
PMID- 25115225
TI - Left atrial metastasis of renal cell carcinoma: a case report and review of the
literature.
AB - BACKGROUND: Cardiac metastasis of renal cell carcinoma is an exceptional event,
particularly when there is lack of inferior vena cava involvement. Indeed, only a
few cases have been reported worldwide thus far. Moreover, discussion of
treatment and follow-up strategies for cardiac metastasis of renal cell carcinoma
is important because of the high risk of sudden death. CASE PRESENTATION: We
report the case of a 75-year-old Japanese man with metastatic tumor in the left
atrium from renal cell carcinoma. He had a history of right renal cell carcinoma,
for which he had undergone hand-assisted laparoscopic nephrectomy. Lung and bone
metastases were detected after nephrectomy, and treatment with interferon-alpha
was initiated. After disease progression, he was treated concurrently with
targeted molecular therapy and radiotherapy for bone metastasis. After these
therapies, a 42 * 24 mm mass was found on transthoracic echocardiography in left
atrium without involvement of the right atrium or inferior vena cava. The
provisional diagnosis was metastatic mass or myxoma, and surgical resection was
performed. Histopathological examination led to a final diagnosis of metastatic
tumor from clear cell renal cell carcinoma. CONCLUSION: Cardiac metastasis,
metastasis to the left atrium in particular, is rare in patients with renal cell
carcinoma. In our study, surgery of the cardiac mass was effective to avoid
sudden death and quality of life decline resulting from heart failure. We
describe this case and review cardiac metastasis of renal cell carcinoma.
PMID- 25115226
TI - Influence of genetic factors on the ephedrine alkaloid composition ratio of
Ephedra plants.
AB - We investigated the ephedrine alkaloid [(-)-ephedrine and (+)-pseudoephedrine]
composition ratio of a crude Chinese herbal drug described in the Japanese
Pharmacopoeia 'Ephedra herb (Chinese name: Mahuang)'. There were marked changes
in the alkaloid composition ratio of wild plants in areas where both male and
female clusters coexisted. However, in genetically homogeneous areas with the
growth of male or female clusters alone, all of the coefficients of the
regression lines were positive, but each gradient varied. This suggests that the
alkaloid composition ratio has a clear tendency in each individual. Based on
this, we cultivated individuals for vegetative propagation, and evaluated the
alkaloid content ratio. Those propagated by separating the roots showed a
specific tendency regardless of the cultivation area (Wakayama, Tanegashima).
Those propagated by separating the herbaceous stem showed a specific tendency
regardless of the soil or harvest time. In addition, we surveyed the (-)
ephedrine content ratio of 3- to 6-year-old strains. There was a high positive
correlation coefficient between the previous and subsequent years. These findings
suggest that the ephedrine alkaloid composition ratio of Ephedra herb depends on
genetic factors, but not on environmental factors or the growth period.
PMID- 25115227
TI - Identification of marker compounds for Japanese Pharmacopoeia non-conforming
jujube seeds from Myanmar.
AB - Jujube seed is a crude drug defined as the seed of Ziziphus jujuba Miller var.
spinosa Hu ex H.F. Chou (Rhamnaceae) in the Japanese Pharmacopoeia (JP). Most of
the jujube seed in the Japanese markets is imported from China, with the rest
obtained from other Asian countries. Here we confirmed the botanical origins of
jujube seeds from both China and Myanmar by a DNA sequencing analysis. We found
that the botanical origins of the crude drugs from China and Myanmar were Z.
jujuba and Z. mauritiana, respectively. Although the jujube seed from China
conforms to the JP, that from Myanmar does not. A method for discriminating
jujube seeds from China and Myanmar using a chemical approach is thus desirable,
and here we sought to identify a compound specific to Z. jujuba. Jujuboside A (1)
was identified as a compound specific to Z. jujuba. To establish a purity test of
Jujube Seed in the JP against Z. mauritiana, we fractionated the extract of Z.
mauritiana seeds and identified frangufoline (2) and oleanolic acid (4) as the
marker compounds specific to Z. mauritiana. Thin-layer chromatography (TLC) and
gas chromatography-mass spectrometry analyses revealed that the latter compound
was useful for testing by TLC analysis. The established TLC conditions were as
follows: chromatographic support, silica gel; developing solvent, n
hexane:EtOAc:HCOOH = 10:5:1; developing length, 7 cm; visualization, diluted
sulfuric acid; R f value, 0.43 (oleanolic acid).
PMID- 25115228
TI - FERTILITY INTENTIONS AND EARLY LIFE HEALTH STRESS AMONG WOMEN IN EIGHT INDIAN
CITIES: TESTING THE REPRODUCTIVE ACCELERATION HYPOTHESIS.
AB - In life history theory, early life adversity is associated with an accelerated
reproductive tempo. In harsh and unpredictable conditions in developing societies
fertility is generally higher and the reproductive tempo faster than in more
secure environments. This paper examines whether differences in female
anthropometry, particularly adult height, are associated with fertility
intentions of women in urban environments in India. The study population consists
of women aged 15-29 (N=4485) in slums and non-slums of eight Indian cities in the
National Family Health Survey (NFHS) of 2005-2006. Adult height is taken as a
proxy for early childhood health and nutritional condition. Fertility intentions
are examined by using two variables: the desire to have a child or another child,
and to have it relatively soon, as indicative of accelerated reproductive
scheduling. Evidence supporting the acceleration hypothesis is found in two urban
frames out of 26 examined in a two-staged multinomial logistic model. In three
cases, the relationship between fertility intentions and height is the opposite
than expected by the acceleration hypothesis: taller women have a higher
predictive probability of desiring a(nother) child and/or narrower birth spacing.
Potential explanations for the partly contradictory relationship between the
childhood health indicator and fertility intentions are discussed.
PMID- 25115231
TI - Experience using a rapid assay for aneuploidy and microdeletion/microduplication
detection in over 2,900 prenatal specimens.
AB - BACKGROUND: While microarray testing can identify chromosomal abnormalities
missed by karyotyping, its prenatal use is often avoided in low-risk pregnancies
due to the possible identification of variants of uncertain significance (VOUS).
METHODS: We tested 2,970 prenatal samples of all referral indications using a
rapid BACs-on-Beads-based assay with probes for sex chromosomes, common autosomal
aneuploidies, and 20 microdeletion/microduplication syndromes, designed as an
alternative to microarray in low-risk pregnancies and an alternative to rapid
aneuploidy testing in pregnancies also undergoing microarray analysis. RESULTS:
Interpretable results were obtained in 2,940 cases (99.0%), with 89% receiving
results in 1 day. Aneuploidies were detected in 7.3% and partial chromosome
abnormalities in 0.45% (n = 13), including 5 referred for maternal age, abnormal
maternal serum screen, or isolated ultrasound markers. The added detection above
karyotype was 1 in 745 in lower-risk cases with normal ultrasounds or isolated
ultrasound markers/increased nuchal measurements and 1 in 165 for fetuses with
structural/growth abnormalities. Neither false negatives nor false positives were
found within test limitations. Female polyploidy could not be detected, while
polyploidies with Y chromosomes were suspected and confirmed through additional
analysis. CONCLUSION: When combined with karyotyping, this assay provides
increased interrogation of specific chromosomal regions, while limiting VOUS
identification.
PMID- 25115230
TI - Clinical evaluation of resin-based composites in posterior restorations: a 3-year
study.
AB - OBJECTIVES: The aim of this study was to evaluate the clinical performance of a
nanohybrid and a microhybrid composite in class I and II restorations after 3
years. SUBJECTS AND METHODS: A total of 82 class I and class II restorations were
performed in 31 patients (10 males and 21 females) using Grandio and QuiXfil with
self-etch adhesives (Futurabond and Xeno III). The restorations were clinically
evaluated by 2 operators 1 week after placement (baseline) and at 6 months and 1,
2, and 3 years using modified United States Public Health Service (USPHS)
criteria. At the 3-year follow-up, 62 class I and class II cavities were
reevaluated in 23 patients (7 males and 16 females). Statistical analysis was
performed using Pearson's chi(2) and Fisher's exact tests (p < 0.05). RESULTS: At
the 6-month follow-up, all restorations received Alfa scores with respect to each
evaluation criterion. At the 1-year follow-up, 2 QuiXfil restorations had to be
replaced and Grandio restorations started to deteriorate in terms of marginal
adaptation. At the end of 2 years, 9 Grandio restorations showed significant
deterioration of the surface properties, demonstrating Bravo scores. At the end
of 3 years, no significant differences were observed regarding color match,
marginal adaptation, secondary caries, marginal discoloration, and anatomic form
loss between the evaluated materials in 25 class I and 37 class II restorations.
At the 3-year follow-up, Grandio restorations had 21% Bravo scores and showed
significant deterioration of the surface properties, which were still clinically
acceptable according to USPHS criteria. Three QuiXfil and 1 Grandio restorations
were replaced because of secondary caries and loss of retention. CONCLUSIONS:
Both the nanohybrid (Grandio) and the microhybrid (QuiXfil) composites were
clinically functional after 3 years.
PMID- 25115232
TI - Systematic review of proximal femoral arthroplasty for non-neoplastic conditions.
AB - Proximal femoral arthroplasty (PFA) is an established treatment modality
following oncological resection. Increasingly, these prostheses are being used
for non-neoplastic conditions such as fractures and bone loss associated with
septic or aseptic loosening. We performed a systematic review of the literature
to determine the failure rates, mortality rates and hip outcome scores when PFAs
were used in non-neoplastic conditions. There were 14 studies with an average
follow-up of 3.8 years (range 0-14 years) describing 356 PFAs. Re-operation for
any reason occurred in 23.8% (85/356) of cases. The most common complications
were dislocation (15.7%) and infection (7.6%). The mortality rate ranged from 0%
to 40%. PFA provides an acceptable surgical solution when confronted with massive
bone loss, but it has a high re-operation rate for dislocation and infection.
PMID- 25115233
TI - RDOS-family: a guided learning tool for layperson assessment of respiratory
distress.
PMID- 25115235
TI - Locked tension band wiring using ring pins for patellar fractures: a method of
minimising implant migration.
AB - BACKGROUND: A modified K-wire attached with ring (ring pin) was used to treat a
displaced patellar fracture, and the ring pin was locked with tension band
wiring. The purpose of this study was to evaluate the surgical outcome of this
method with respect to its procedural safety. METHODS: The authors
retrospectively reviewed 36 patients treated for a displaced patellar fracture
and assessed bone union, fixation failure, postoperative pain, range of motion,
and incidence of hardware removal. Clinical outcome was evaluated using the
Bostman scoring system. The mean follow-up period was 27 (range 13-47) months.
RESULTS: Bony union was achieved in all patients. No fixation failure and pin
migration were detected. Hardware was removed in three cases (8.3 %). Reasons for
removal were pain in one case and vague discomfort in two cases. The average
Bostman scores at 12 months postoperatively were 29.6, with 34 (94.4 %) patients
graded as excellent. The average active flexion of the knee joint was 130.4
degrees (range 125 degrees -150 degrees ), with an average flexion contracture
of 3 degrees (range 0 degrees -10 degrees ). CONCLUSIONS: This implant could
facilitate satisfactory fixation, restore the integrity of the extensor
mechanism, and reduce the possibility of implant migration and implant-related
discomfort.
PMID- 25115234
TI - The risk of second primary malignancy is increased in differentiated thyroid
cancer patients with a cumulative (131)I dose over 37 GBq.
AB - BACKGROUND: The aim of this study was to investigate the risk factors for second
primary malignancy (SPM) diagnosed after differentiated thyroid cancer (DTC).
METHODS: A total of 2468 DTC patients who underwent thyroidectomy were reviewed.
SPM was defined as a non-thyroidal malignancy, diagnosed at least 1 year after
the diagnosis of thyroid cancer. Patients were divided into five groups according
to cumulative (131)I dose: very high-activity (>= 37.0 GBq), high-activity (22.3
36.9 GBq), intermediate-activity (5.56-22.2 GBq), low-activity (1.1-5.55 GBq) and
no RAI. RESULTS: Among the 2468 patients, 61 (2.5%) had SPMs during 7.0 (1.0
33.0) years of median follow-up. Age above 40 years, male sex and very high
activity RAI were independent risk factors for the development of SPM. SPM
related mortality was highest in the very high-activity group, while DTC-related
mortality was highest in the high-activity group. The overall mortality both from
SPM and DTC was highest in the high-activity group. CONCLUSION: A cumulative
(131)I dose <37.0 GBq did not increase the risk of SPM. A cumulative (131) I dose
>= 37.0 GBq increased the risk of SPM and SPM-related mortality and decreased the
DTC-specific mortality, resulting in a similar all-cause mortality compared with
the low-activity RAI group. Using repeated high-dose RAI for treating RAI
responsive but persistent DTC patients needs careful consideration of the
individual benefits from RAI vs the risk of developing SPM.
PMID- 25115236
TI - Diffusion and diversion of suboxone: an exploration of illicit street opioid
selling.
AB - Interviews with fourteen opioid retail pill sellers provides an exploration into
the diversion and diffusion of Suboxone to recreational ("week-end warriors")
drug users. The use of social media and electronic devices enables the diffusion
of Suboxone to dependent and non-dependent opiate/opioid drug abusers.
Overprescribing by physicians and prescribing in drug treatment settings fuels
the diversion of Suboxone. The diversion and the diffusion of Suboxone have the
potential to delay entrance into drug treatment and promote the misuse of the
drug by both dependent opiate/opioid drug abusers and recreational users. The
dilemma posed by Suboxone maintenance treatment will not be easily addressed or
mitigated in the near future.
PMID- 25115238
TI - Unmet needs in the treatment of psoriasis.
AB - Biologics have greatly improved the treatment of moderate-to-severe plaque
psoriasis, as most patients are now able to achieve an initial improvement of 75%
in the Psoriasis Area and Severity Index. However, only ~20%-57% reach a 90%
improvement in this measurement and responses may be lost over time. In addition,
there are potential safety issues as TNF-inhibitor biologics have been associated
with infections or non-melanoma skin malignancies. Here we review unmet needs
with current therapies for psoriasis. We researched the medical literature to
discuss new therapies in development and assess their potential to meet these
needs. Several new classes of anti-psoriatic drugs are currently undergoing
clinical development and potential improvements with these new therapies include
attaining earlier and higher-level responses that are durable, more specific
targeting of cytokines involved directly in psoriatic inflammation, and new
therapies offering convenient administration. Additionally, based on results from
clinical trials evaluating these new agents, it may be possible to find
predictive markers that identify patients best treated with certain drug classes,
those prone to lose treatment responses and patients who can discontinue
treatment and remain in remission. It remains to be determined whether the
promising results seen in early studies of therapies in development for psoriasis
will translate into actual improvements over currently available treatment
options.
PMID- 25115237
TI - Brachyury cooperates with Wnt/beta-catenin signalling to elicit primitive-streak
like behaviour in differentiating mouse embryonic stem cells.
AB - BACKGROUND: The formation of the primitive streak is the first visible sign of
gastrulation, the process by which the three germ layers are formed from a single
epithelium during early development. Embryonic stem cells (ESCs) provide a good
system for understanding the molecular and cellular events associated with these
processes. Previous work, both in embryos and in culture, has shown how
converging signals from both nodal/TGFbetaR and Wnt/beta-catenin signalling
pathways specify cells to adopt a primitive-streak-like fate and direct them to
undertake an epithelial-to-mesenchymal transition (EMT). However, many of these
approaches have relied on genetic analyses without taking into account the
temporal progression of events within single cells. In addition, it is still
unclear to what extent events in the embryo are able to be reproduced in culture.
RESULTS: Here, we combine flow cytometry and a quantitative live single-cell
imaging approach to demonstrate how the controlled differentiation of mouse ESCs
towards a primitive streak fate in culture results in cells displaying many of
the characteristics observed during early mouse development including transient
brachyury expression, EMT and increased motility. We also find that the EMT
initiates the process, and this is both fuelled and terminated by the action of
brachyury, whose expression is dependent on the EMT and beta-catenin activity.
CONCLUSIONS: As a consequence of our analysis, we propose that a major output of
brachyury expression is in controlling the velocity of the cells that are
transiting out of the primitive streak.
PMID- 25115240
TI - Melomics music medicine (M3) to lessen pain perception during pediatric prick
test procedure.
PMID- 25115239
TI - Retrospective observational study of diagnostic accuracy of the Xpert(r) MTB/RIF
assay on fiberoptic bronchoscopy sampling for early diagnosis of smear-negative
or sputum-scarce patients with suspected tuberculosis.
AB - BACKGROUND: Fiberoptic bronchoscopy (FOB) is a useful diagnosis tool in low
burden countries for patients with suspected pulmonary tuberculosis (TB) who are
smear-negative or sputum-scarce. This study sought to determine the accuracy of
the Xpert(r) MTB/RIF (XP) assay using FOB samples. METHODS: We retrospectively
reviewed clinical, radiological, and microbiological characteristics of 175 TB
suspected patients requiring diagnostic FOB (bronchial aspirate or
bronchoalveolar lavage) with XP assay. Polymerase chain reaction (PCR) and smear
microscopy (SM) performances were first compared to culture, then to the final
diagnosis, established based on clinical or radiological evolution when cultures
were negative. RESULTS: Of the total 162 included patients, 30 (18.5%) had a
final diagnosis of pulmonary TB, with positive cultures reported in 23. As
compared to culture, sensitivity and specificity values were 80.0% and 98.6% for
the XP assay, and 25.0% and 95.8% for SM, respectively. As compared to final
diagnosis, the corresponding performance values were 60.0% and 100.0% for the XP
assay, and 16.7% and 95.5% for SM, respectively. The sensitivity of the XP assay
was significantly higher than that of SM in both cases (p=0.003 and p=0.001).
Concerning the final diagnosis, both XP assay and culture sensitivities were
similar (60% vs. 66.7%). PCR assay enabled pulmonary TB to be diagnosed earlier
in 13 more cases, compared to SM. CONCLUSION: Our study has confirmed the
clinical benefits provided by XP assay compared to SM for the early diagnosis of
suspected pulmonary TB cases requiring FOB, on per procedure samples, especially
in a low TB-burden country.
PMID- 25115241
TI - Selective-area epitaxy of pure wurtzite InP nanowires: high quantum efficiency
and room-temperature lasing.
AB - We report the growth of stacking-fault-free and taper-free wurtzite InP nanowires
with diameters ranging from 80 to 600 nm using selective-area metal-organic vapor
phase epitaxy and experimentally determine a quantum efficiency of ~50%, which is
on par with InP epilayers. We also demonstrate room-temperature, photonic mode
lasing from these nanowires. Their excellent structural and optical quality opens
up new possibilities for both fundamental quantum optics and optoelectronic
devices.
PMID- 25115242
TI - Conjugative transfer of ICESde3396 between three beta-hemolytic streptococcal
species.
AB - BACKGROUND: Integrative conjugative elements (ICEs) are mobile genetic elements
(MGEs) that possess all genes necessary for excision, transfer and integration
into recipient genome. They also carry accessory genes that impart new phenotypic
features to recipient strains. ICEs therefore play an important role in genomic
plasticity and population structure. We previously characterised ICESde3396, the
first ICE identified in the beta-hemolytic Streptococcus dysgalactiae subsp
equisimilis (SDSE) and demonstrated its transfer to single isolates of
Streptococcus pyogenes (group A streptococcus, GAS) and Streptococcus agalactiae
(group B streptococcus, GBS). While molecular studies found the ICE in multiple
SDSE and GBS isolates, it was absent in all GAS isolates examined. RESULTS: Here
we demonstrate that ICESde3396:km is transferable from SDSE to multiple SDSE, GAS
and GBS isolates. However not all strains of these species were successful
recipients under the same growth conditions. To address the role that host
factors may have in conjugation we also undertook conjugation experiments in the
presence of A549 epithelial cells and DMEM. While Horizontal Gene Transfer (HGT)
occurred, conjugation efficiencies were no greater than when similar experiments
were conducted in DMEM. Additionally transfer to GAS NS235 was successful in the
presence of DMEM but not in Todd Hewitt Broth suggesting that nutritional factors
may also influence HGT. The GAS and GBS transconjugants produced in this study
are also able to act as donors of the ICE. CONCLUSION: We conclude that ICEs are
major sources of interspecies HGT between beta-hemolytic streptococci, and by
introducing accessory genes imparting novel phenotypic characteristics, have the
potential to alter the population structure of these species.
PMID- 25115243
TI - Antiviral efficacy and safety of abacavir-containing combination antiretroviral
therapy as first-line treatment of HIV-infected children and adolescents: a
systematic review protocol.
AB - BACKGROUND: Abacavir is one of the recommended nucleoside reverse transcriptase
inhibitors (NRTIs) for the treatment of HIV infections among children and
adolescents. However, there are concerns that the antiviral efficacy of abacavir
might be low when compared to other NRTIs especially among children. There are
also concerns that abacavir use may lead to serious adverse events such as
hypersensitivity reactions and has potential predisposition to developing
cardiovascular diseases. METHODS: We plan to do a systematic review to evaluate
the antiviral efficacy and safety of abacavir-containing combination
antiretroviral therapy as first-line treatment of HIV-infected children aged
between 3 months and 18 years, compared with other NRTIs. We will search Scopus,
Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science
databases for eligible studies regardless of language or publication status. We
will check the reference lists of included studies, search relevant conference
proceedings, email the authors of included studies and also look for unpublished
and ongoing trials in prospective clinical trial registries. Two authors will
independently screen search outputs, select studies, extract data and assess the
risk of bias in included studies. All disagreements will be resolved by
discussion and consensus. Where data allow, we will conduct meta-analysis for
similar types of participants, study designs, interventions, and outcome
measures. If the results are statistically homogeneous, we will use the fixed
effect model; otherwise, we will use the random-effects model and explore the
reasons for heterogeneity using subgroup analyses. Heterogeneity will be assessed
with the Chi-squared test and quantified with the I-squared statistic.
DISCUSSION: The findings will be useful to policy makers and programme managers
to inform treatment and management of HIV in children and adolescents and to
point out research gaps for future research. TRIAL REGISTRATION: This review is
registered with PROSPERO, registration number CRD42014009157.
PMID- 25115244
TI - Microvolt T-wave alternans profile in patients with pulmonary arterial
hypertension.
PMID- 25115245
TI - Personalized CHF treatment: PCT to guide therapy in heart failure patients.
AB - Sorting out the etiology of dyspnea in patients with a history of heart failure
is not always straightforward. Although an acute heart failure exacerbation would
seem to be easy to distinguish from an acute respiratory illness, data from
objective clinical studies has shown otherwise. Procalcitonin (PCT), a biomarker
that rises in the setting of bacterial infection, carries great potential for
guiding the diagnosis and treatment of heart failure patients with possible acute
respiratory infection. In this issue of the International Journal of Cardiology,
Kutz et al. demonstrated that patients with a history of heart failure and
suspected lower respiratory tract infection experienced reduced antibiotic
duration and superior outcomes with PCT-guided therapy. The results in this
subset of heart failure patients from the ProHOSP study were consistent with the
results seen in the overall study population. This study points to the need for a
randomized controlled trial in a broader population of heart failure patients
with acute dyspnea, to further define the prominent role that PCT can play in
more personalized medical treatments that can improve patient outcomes.
PMID- 25115246
TI - Effects of OX40-OX40 ligand interaction on the levels of ROS and Cyclophilin A in
C57BL/6J mice atherogenesis.
AB - BACKGROUND: An increasing amount of evidence shows that the OX40-OX40L
interaction serves an important function in atherosclerosis. However, the
mechanism of the OX40 signaling pathway remains unclear. This study investigates
the effect of OX40-OX40L interaction on the levels of intracellular reactive
oxygen species (ROS) and the secretion of Cyclophilin A (CyPA) in C57BL/6J mice
atherogenesis. METHODS: The atherosclerotic plaque model was established by
placing a rapid perivascular carotid collar on C57BL/6J mice fed with a western
type diet. In vivo, the expressions of CyPA in mouse plaque and lymphocytes were
detected by immunohistochemical and Western blot analyses, respectively. In
vitro, the expression of CyPA protein in cultured lymphocytes of C57BL/6J mice
was assessed by using Western blot analysis. The level of ROS was detected
through flow cytometry. RESULTS: CyPA expression was significantly increased in
the atherosclerotic lesions and lymphocytes from C57BL/6J mice. The ROS levels in
OX40(+)-lymphocytes were increased in vitro and in vivo. After stimulating the
OX40-OX40L interaction, the ROS and CyPA levels in lymphocytes were obviously
increased in vitro, whereas anti-OX40L mAb significantly down-regulated the anti
OX40 mAb-induced ROS generation and inhibited CyPA secretion in lymphocytes.
CONCLUSION: The OX40-OX40L interaction up-regulates intracellular levels of ROS
in C57BL/6J mice and increases CyPA secretion in lymphocytes. Increased CyPA
secretion may serve an important function in atherosclerotic plaque formation.
PMID- 25115247
TI - The value of CHADS2 score in predicting new-onset atrial fibrillation in Chinese
patients with acute myocardial infarction.
PMID- 25115248
TI - Bioabsorbable stent thrombosis Quo Vadis: is Kounis syndrome still present?
PMID- 25115249
TI - Albumin may prevent hypertension by inhibiting renin angiotensin aldosterone
system.
PMID- 25115250
TI - Maternal NT-proBNP in chronic hypertensive pregnancies and superimposed
preeclampsia.
PMID- 25115251
TI - QRS fragmentation and epsilon waves in Fontaine leads in arrhythmogenic right
ventricular cardiomyopathy: re: "The use of fontaine leads in the diagnosis of
arrhythmogenic right ventricular dysplasia" and "Arrhythmogenic right ventricular
cardiomyopathy: contribution of different electrocardiographic techniques".
PMID- 25115252
TI - Out-of-hospital versus in-hospital Takotsubo cardiomyopathy: analysis of 3719
patients in the Diagnosis Procedure Combination database in Japan.
AB - BACKGROUND: Although Takotsubo cardiomyopathy (TC) generally occurs after a
stressful event out-of-hospital, it occasionally occurs secondary to acute
medical illness after hospital admission. No study has examined and compared
patient backgrounds and in-hospital outcomes between patients with out-of
hospital TC and those with in-hospital TC. METHODS AND RESULTS: Using the
Diagnosis Procedure Combination inpatient database in Japan, we identified 3719
eligible patients with a diagnosis of TC who underwent coronary angiography
without any revascularization procedure between 2010 and 2013, including 419
patients with in-hospital TC and 3300 patients with out-of-hospital TC. There was
no significant difference in age between those with in-hospital TC and those with
out-of-hospital TC (74.2 +/- 10.9 years versus 73.4 +/- 11.3 years, p=0.211).
Patients with in-hospital TC had a higher proportion of males than out-of
hospital TC patients (31.3% versus 21.3%, p<0.001). Patients with in-hospital TC
had significantly higher proportions of several chronic comorbidities and acute
medical illnesses. In-hospital mortality was significantly higher in patients
with in-hospital TC than in patients with out-of-hospital TC (17.9% versus 5.4%,
p<0.001). In the multivariable logistic regression analysis, in-hospital TC was
significantly associated with higher in-hospital mortality (adjusted odds ratio
2.02; 95% confidence interval, 1.43 to 2.85; p<0.001), even after adjustment for
patient backgrounds. Malignancy, chronic liver disease, rheumatic disease,
sepsis, pneumonia, cerebrovascular diseases, acute renal failure, and acute
gastrointestinal diseases were also significantly associated with higher in
hospital mortality. CONCLUSIONS: In-hospital TC was associated with more severe
clinical background and poorer short-term prognosis than out-of-hospital TC.
PMID- 25115253
TI - Evaluation of the clinical use of midregional pro-atrial natriuretic peptide (MR
proANP) in comparison to N-terminal pro-B-type natriuretic peptide (NT-proBNP)
for risk stratification in patients with light-chain amyloidosis.
PMID- 25115254
TI - The relationship between epicardial fat thickness and arterial stiffness; role of
antihypertensive drugs and statins.
PMID- 25115255
TI - Renal denervation: does prior renal stenting really matter?
PMID- 25115257
TI - Air pollution and the risk of stroke by meta-analysis.
PMID- 25115256
TI - Extreme bradycardia associated with nebivolol therapy.
PMID- 25115258
TI - Rates of aldosterone antagonist use after myocardial infarction remain poor over
time among guideline eligible patients.
PMID- 25115259
TI - Ambulatory blood pressure may be designed as the primary efficacy outcome in
clinical trials on renal denervation.
PMID- 25115260
TI - Reversible attenuation of the amplitude of the electrocardiogram QRS complexes in
a patient with Takotsubo syndrome: a quantitative analysis.
PMID- 25115261
TI - Fibrinolysis in intermediate risk pulmonary embolism: too much risk for too
little reward?
PMID- 25115262
TI - Blood pressure components and stroke in Inner Mongolians--a prospective cohort
study.
PMID- 25115263
TI - Elevated concentrations of high-density lipoprotein cholesterol and
cardiovascular risk paradox in patients with coronary heart disease and the
equivalents.
PMID- 25115265
TI - FGF23 and risk of all-cause mortality and cardiovascular events: a meta-analysis
of prospective cohort studies.
PMID- 25115264
TI - Coronary artery fistula: comparison of diagnostic accuracy by echocardiography
versus coronary arteriography and surgery in 63 patients studied between 2002 and
2012 in a single medical center in China.
AB - BACKGROUND: Coronary artery fistula (CAF) is a rare congenital anomaly, which is
conventionally diagnosed by coronary arteriography; however, the relation of the
coronary artery fistulas to other structures, their origin and course may not be
always apparent. METHODS: The echocardiograms of 63 patients with coronary artery
fistulas, who had undergone coronary arteriography and/or surgery from June 2002
to December 2012 at the Union Hospital, Tongji Medical College, Huazhong
University of Science and Technology, were analyzed retrospectively, and the
results were compared with findings by coronary arteriography and at surgery.
RESULTS: Right CAFs were detected in 33 of the 63 patients (52.4%); 11 had
drainage to the right atrium, 10 to the right ventricle, 2 to the left ventricle,
9 to the main pulmonary artery, and 1 to the coronary sinus. Left CAFs were
detected in 29 patients (46.0%); 6 had drainage to the right atrium, 12 to the
right ventricle, 1 to the left atrium, 2 to the left ventricle, 7 to the main
pulmonary artery, and 1 to the coronary sinus. One patient (1.6%) had the origin
of the fistula in both coronary arteries. The entry point of the fistula was most
often a single orifice (96.8%) and rarely multi-orificial (3.2%). 57 patients
(90.5%) had isolated coronary fistulas (90.5%); 6 patients (9.5%) had other
congenital cardiac malformations. The ultrasonic diagnosis of 60 patients was in
line with findings at surgery and/or coronary arteriography. The diagnostic
accuracy rate for coronary artery fistula was 95.2%. Preoperative transthoracic
echocardiography missed the diagnosis of coronary artery fistula in three
patients (4.8%). There is no difference (P>0.05) in diagnostic accuracy between
echocardiography and coronary arteriography and/or surgery. CONCLUSIONS:
Transthoracic echocardiography, in comparison with coronary arteriography and/or
surgery, is much simpler, easier, less expensive, safer, readily repeatable, and
more convenient with equal accuracy, and should be the first-line method for the
diagnosis of congenital coronary artery fistula.
PMID- 25115266
TI - Comparison of pooled cohort risk equations and Framingham risk score for
metabolic syndrome in a Korean community-based population.
PMID- 25115267
TI - Pitavastatin decreases serum LOX-1 ligand levels and MT1-MMP expression in CD14
positive mononuclear cells in hypercholesterolemic patients.
PMID- 25115268
TI - Non-culprit coronary vasospasm in a woman affected by Churg-Strauss syndrome
presenting with ST-elevation myocardial infarction.
PMID- 25115269
TI - SYNTAX-score based assessment of appropriate candidates for percutaneous coronary
intervention among patients with chronic total occlusion.
PMID- 25115270
TI - Multiplane spectroscopic whole-body photoacoustic imaging of small animals in
vivo.
AB - We have successfully developed a multiscale acoustic-resolution photoacoustic
tomography system in a single imaging platform. By switching between ultrasound
transducers (center frequencies 5 and 40 MHz) and optical condensers, we have
photoacoustically imaged microvasculatures of small animals in vivo at different
scales. Further, we have extended the field of view of our imaging system to
entire bodies of small animals. At different imaging planes, we have
noninvasively imaged the major blood vessels (e.g., descending aorta, intercostal
vessels, cephalic vessels, brachial vessels, femoral vessels, popliteal vessels,
lateral marginal vessels, cranial mesenteric vessels, mammalian vessels, carotid
artery, jugular vein, subclavian vessels, iliac vessels, and caudal vessels) as
well as intact internal organs (e.g., spleen, liver, kidney, intestine, cecum,
and spinal cord) of the animals in vivo. The spectroscopic whole-body
photoacoustic imaging clearly reveals the spectral responses of the internal
structures. Similar to other existing preclinical whole-body imaging systems,
this whole-body photoacoustic tomography can be a useful tool for small-animal
research.
PMID- 25115271
TI - Perceptions and attitudes of pharmacy students towards volunteering at health
promotional programs: a cross-sectional study from Malaysia.
AB - The present study aims to explore the perceptions and understanding of future
pharmacists towards volunteerism in health promotional activities. The study was
designed as a cross sectional, descriptive survey. All pharmacy undergraduates (n
= 293) from the first, second and third professional years enrolled at the School
of Pharmaceutical Sciences, Universiti Sains Malaysia were targeted for the
study. A pre validated, 15-itemed questionnaire was used for data collection and
was analysed by using SPSS. Dichotomous groups were compared with Mann-Whitney U
test. The Jonckheere-Terpstra test was used to evaluate the trend of association.
Where significant associations were reported, effect size was calculated by using
Kendall tau correlation coefficient. p value of <0.05 was considered to be of
statistical significance. Out of 200 respondents, 185 completed the study with a
response rate of 92.5 %. Agreement with mandatory status of volunteerism at
community services was significant with gender (p = 0.003) and year of study (p =
0.045). Confidence in performing health promotional activities (p = 0.001, tau =
0.155) and needed communication skills during health promotional activities (p =
0.022, tau = 0.322) were also significantly associated with year of study with a
moderate positive trend from junior to senior classes. Although pharmacy
undergraduates showed positive interest and will to volunteer at the health
promotional programs, certain issues were also highlighted. Therefore, in order
to address these challenges, pharmacy curriculum needs to include a greater
emphasis on role of pharmacists in public health. This can be achieved by having
a dedicated core course as part of pharmacy curriculum.
PMID- 25115272
TI - Spontaneous Nephrocutaneous Fistula: A Case Report, Update of the Literature and
Management Algorithm.
AB - AIMS: Spontaneous nephrocutaneous fistula (NCF) is a rare and severe condition.
The aim of this study was to update the data of the literature about this disease
and, reporting and considering also our experience in 1 case of NCF, to make a
new clinical algorithm. METHODS: This study was done with a review of all the
literature and a comparison with our experience. RESULTS: The characteristic sign
of spontaneous NCF is a flank sinus discharging material. Physical examination
and computed tomography usually lead to the diagnosis. The main predisposing
factors are renal stones/staghorn calculi, xanthogranulomatous pyelonephritis and
renal tuberculosis. In the vast majority of the cases kidneys are poorly
functioning or nonfunctioning. Surgical approach is the common management and
usually consists of open nephrectomy. We create a clinical management algorithm
obtained by a review of the literature and our experience with spontaneous NCF.
CONCLUSIONS: Spontaneous NCF represents a very serious renal disease leading to
loss of the kidney in the vast majority of cases. We propose a revised and user
friendly clinical diagnostic-therapeutic algorithm for spontaneous NCF based on
the worldwide literature.
PMID- 25115274
TI - Cancer survivorship and palliative care?
PMID- 25115273
TI - Maternal organ donation and acute injuries in surviving children.
AB - PURPOSE: The purpose of this study is to test whether maternal deceased organ
donation is associated with rates of subsequent acute injuries among surviving
children after their mother's death. METHODS: This is a longitudinal cohort
analysis of children linked to mothers who died of a catastrophic brain event in
Ontario, Canada, between April 1988 and March 2012. Surviving children were
distinguished by whether their mother was an organ donor after death. The primary
outcome was an acute injury event in surviving children during the year after
their mother's death. RESULTS: Surviving children (n=454) had a total of 293
injury events during the year after their mother's death, equivalent to an
average of 65 events per 100 children per year and a significant difference
comparing children of mothers who were organ donors to children of mothers who
were not organ donors (21 vs 82, P<.001). This difference in subsequent injury
rates between groups was equal to a 76% relative reduction in risk (95%
confidence interval, 62%-85%). CONCLUSIONS: Deceased organ donation was
associated with a reduction in excess acute injuries among surviving children
after their mother's death. An awareness of this positive association provides
some reassurance about deceased organ donation programs.
PMID- 25115275
TI - Reproductive pattern of Cuban women living in the municipality of Plaza de la
Revolucion, Havana, Cuba.
AB - This paper assesses the reproductive and abortion patterns of women living in
Plaza de la Revolucion, a municipality of Havana, Cuba, by studying the factors
influencing birth and abortion rates. Socio-demographic data and female
reproductive histories were collected in a survey of 1200 post-menopausal women
living in the municipality. Average ages at menarche and at menopause were 12.71
and 48.39 years, respectively, thus yielding a potential long reproductive period
of 35.68 years, indicating high fertility. Although the mean pregnancy rate was
3.81 pregnancies per woman, the live birth rate at time of delivery was only 1.89
due to the high rate of abortions: 40% of all pregnancies were voluntarily
interrupted. Among the biological and socio-cultural variables that were found to
influence the rate of live births were those related marriage pattern, especially
age at first union. Demographic variables such as pregnancy order, maternal age
and marital status were the main determinants of the abortion pattern, with
abortion being used as a method of birth control in order to obtain the desired
family size, and most women (75.2%) using contraceptives.
PMID- 25115276
TI - Better late than never: the perceived benefits of smoking cessation among women
in late midlife.
AB - The current study examined the association of smoking cessation (>=1 year without
relapse) and self-reported psychosocial and physical outcomes among a community
sample of women (N = 195; mean age = 63.7 years, SD = 5.7 years). Data were
collected in 1985-1986 and 2009. Successful smoking cessation for >=1 year was
significantly associated with each of the outcome measures (e.g., less financial
stress [adjusted odds ratio (AOR) = 0.50; 95% confidence interval (CI) = 0.25
1.00, P< 0.05), less life dissatisfaction (AOR = 0.51, 95% CI = 0.24-1.09, P<
0.05). Findings suggest that older women should be included in smoking cessation
programs, and the important benefits of quitting should be used to encourage
cessation.
PMID- 25115277
TI - The impact of maternal obesity, age, pre-eclampsia and insulin dependent diabetes
on severe maternal morbidity by mode of delivery-a register-based cohort study.
AB - PURPOSE: To determine the rate of severe maternal morbidity related to delivery
by delivery mode and to assess if the impact of studied risk factors varies by
delivery mode. METHODS: A register-based study including all women having
singleton delivery in Finland in 2007-2011, n = 292,253, data derived from the
Finnish Medical Birth Registry and Hospital Discharge Registry. Diagnoses and
interventions indicating a severe maternal complication were searched and the
mode of delivery was assessed by data linkage. The impact of obesity, maternal
age 35 years or more, pre-eclampsia and insulin dependent diabetes on severe
maternal morbidity (all severe complications, severe infections and severe) was
studied in each mode of delivery and calculated as Odds ratios. RESULTS: The
overall incidence of severe complications was 12.8/1,000 deliveries. The total
complication rate was lowest in vaginal deliveries (VD) in all risk groups.
Obesity increased the risk for all severe complications and severe infections in
the total population, but not significantly in specific delivery modes. Age
increased the risk of hemorrhage in VD. Pre-eclampsia increased the risk for
hemorrhage in all deliveries except elective CS. In women with pre-eclampsia,
overall morbidity was similar in VD, attempted VD and elective CS. The presence
of any studied risk factor increased the risk for complications within the risk
groups by the high proportion of emergency CS performed. CONCLUSIONS: An attempt
of VD is the safest way to deliver even for high-risk women with the exception of
women with pre-eclampsia, who had a similar risk in an attempt of VD and elective
CS.
PMID- 25115278
TI - Anti-tumour activity of phosphoinositide-3-kinase antagonist AEZS-126 in models
of ovarian cancer.
AB - PURPOSE: Platinum resistance is the most crucial problem for treatment of ovarian
cancer. There is a clinical need for new treatment strategies which overcome
platinum resistance. Recently high level of AKT was shown to be involved in
platinum resistance and furthermore in resistance against Natural-killer (NK)
cell mediated killing in ovarian cancer. METHODS: Here, we investigate the
ability of the PI3K/AKT inhibitor AEZS-126 alone and in combination with
rapamycin to selectively target ovarian cancer cell proliferation and survival in
vitro by MTT-assays and FACS based analysis. Furthermore the mechanism of
cytotoxicity is analysed by FACS based assays. The NK-killing efficiency of
ovarian cancer cells with and without pre-treatment with AEZS-126 was analysed.
RESULTS: AEZS-126 showed good anti-tumour activity in in vitro models of ovarian
cancer. Main mechanism of cytotoxicity seems to be necroptosis which could be
abrogated by co-incubation with necrostatin-1. Furthermore pre-treatment of
platinum resistant cells with AEZS-126 resulted in an increased accessibility of
these tumour cells for killing by NK-cells. CONCLUSION: We demonstrated the
highly efficient anti-tumour activity of AEZS-126 in in vitro models of ovarian
cancer. Due to the good anti-tumour activity and the expected increase in NK-cell
mediated killing even of platinum resistant tumour cells, AEZS-126 seems to be a
promising candidate for clinical testing in ovarian cancer.
PMID- 25115279
TI - Slow-freezing versus vitrification for human ovarian tissue cryopreservation.
AB - PURPOSE: Ovarian tissue can be cryopreserved prior to chemotherapy using either
the slow-freezing or the vitrification method; however, the data on the equality
of the procedures are still conflicting. In this study, a comparison of the cryo
damage of human ovarian tissue induced by either vitrification or slow-freezing
was performed. METHODS: Ovarian tissue from 23 pre-menopausal patients was
cryopreserved with either slow-freezing or vitrification. After thawing/warming,
the tissue was histologically and immunohistochemically analyzed and cultured in
vitro. During tissue culture the estradiol release was assessed. RESULTS: No
significant difference was found in the proportion of high-quality follicles
after thawing/warming in the slow-freezing and vitrification group, respectively
(72.7 versus 66.7 %, p = 0.733). Estradiol secretion by the ovarian tissue was
similar between groups during 18 days in vitro culture (area-under-the-curve
5,411 versus 13,102, p = 0.11). Addition of Sphingosine-1-Phosphate or Activin A
to the culture medium did not alter estradiol release in both groups. The
proportion of Activated Caspase-3 or 'Proliferating-Cell-Nuclear-Antigen'
positive follicles at the end of the culture period was similar between slow
freezing and vitrification. CONCLUSION(S): Slow-freezing and vitrification result
in similar morphological integrity after cryopreservation, a similar estradiol
release in culture, and similar rates of follicular proliferation and apoptosis
after culture.
PMID- 25115280
TI - Molecular analysis of miscarriage products using multiplex ligation-dependent
probe amplification (MLPA): alternative to conventional karyotype analysis.
AB - PURPOSE: The present study aims to evaluate whether multiplex ligation-dependent
probe amplification (MLPA) technique with subtelomeric probes is to be an
alternative method of routine G-banding chromosome analysis from pregnancy loss.
METHODS: A review of 5 years (from 2005 to 2009) of karyotype for products of
conception (POCs) was carried out. From June 2010 to June 2012, MLPA was
performed in parallel with karyotype analysis on 347 miscarriages. Karyotyped
miscarriages served as controls in this blinded study. Abnormal results were
confirmed by fluorescence in situ hybridization. RESULTS: A review of 5 years of
karyotype results for POCs indicated that 11.46 % of cases failed to karyotyping.
In the study periods, MLPA results were successfully obtained from all cases
including 51 (14.7 %) culture failed cases, chromosomal abnormalities were
detected in 27 (52.9 %) of cases which failed to grow or could not be cultivated.
It took 3 weeks by conventional karyotyping, but it required at least 24 h and at
most a week by MLPA from tissue sampling to final reporting. 47 cases showed
discordant results between karyotyping and MLPA because of maternal cell
contamination, polyploidy, mosaicism, or balanced translocation. CONCLUSIONS:
MLPA technique is relatively low cost, less labor intensive and reduces waiting
time with high accuracy compared with conventional cytogenetic analysis.
Therefore, MLPA can be the first approach for chromosome analysis from pregnancy
loss.
PMID- 25115281
TI - Cotyledonoid dissecting leiomyoma of the uterus: report of two cases.
AB - BACKGROUND: Cotyledonoid dissecting leiomyoma (Sternberg tumor) is a rare variant
of the uterine smooth muscle tumor. Although this tumor is a benign tumor
clinically and pathologically, the appearance and growth pattern is unusual, so
it may be misdiagnosed as malignancy. CASE REPORTS: We report two cases of
cotyledonoid dissecting leiomyoma of the uterus that occurred in two 44- and 31
year-old women, respectively. Total hysterectomy and bilateral salpingo
oophorectomy were performed in one of the patients, and myomectomy was done in
the other one. Macroscopically, both tumors were grape-like exophytic masses
resembling placental tissue. The patients were well after surgery, and one
patient gave birth. To our knowledge, this is the first case report of a
successful delivery after myomectomy of this tumor. CONCLUSION: To prevent
aggressive surgery it is important to recognize that this tumor is a benign and
unusual appearing variant of leiomyoma. A fertility-sparing surgical procedure
should be considered if the patient wishes to preserve her fertility.
PMID- 25115282
TI - Stage IIIC endometrial cancer: the need for novel subgrouping according to the
ratio of metastatic lymph nodes.
AB - INTRODUCTION: The survival rates in endometrial cancer (EC) patients with lymph
node (LN) metastasis vary greatly. Many other factors may have impact on the
prognosis within this special group. The purpose of this study was to determine
factors predicting the progression or death in patients with stage IIIC EC.
MATERIALS AND METHODS: A single tertiary center, retrospective analysis was
conducted in a total of 38 consecutive patients who surgically treated for EC
between January 2005 and January 2013. The primary endpoint was the determination
of factors predicting the progression, recurrence, or death of any cause. The
secondary endpoints were progression-free survival (PFS) and overall survival
(OS). RESULTS: The median age at diagnosis was 64 years, and the median follow-up
time was 32.50 months (95 % CI 28.75-40.56). The median number of metastatic
positive LNs (pelvic and/or paraaortic) was 2, and the LN ratio, expressed as the
percentage of positive nodes to total LNs identified, was 6.3 %. The LN ratio (>=
6.5 %) was the only independent parameter for progression or death in multiple
logistic regression analysis. Patients were stratified according to the LN ratio
(<6.5 vs. >= 6.5 %) for survival comparisons. The estimated 32-month PFS rates
were 90 and 64.8 %, respectively [HR (95 % CI) = 5.07 (1.05-24.56), P = 0.025].
However, the estimated 32-month OS rates were comparable (94.1 vs. 94.1 %), [HR
(95 % CI) = 4.26 (0.44-41.30), P = 0.21]. DISCUSSION: The stratification of
patients with stage IIIC disease according to the LN ratio may allow better
identification of prognostic information and selection of individualized patient
tailored adjuvant treatment modalities.
PMID- 25115284
TI - Integrated computational materials discovery of silver doped tin sulfide as a
thermoelectric material.
AB - Accelerating the discovery of new materials is crucial for realizing the vision
of need-driven materials development. In the present study we employ an
integrated computational and experimental approach to search for new
thermoelectric materials. High-throughput first principles calculations of
thermoelectric transport coefficients are used to screen sulfide compounds
conforming to the boundary conditions of abundant and innocuous components. A
further computational screening step of substitutional defects is introduced,
whereby SnS doped with monovalent cations is identified as having favorable
transport properties. By silver doping of SnS under S-rich conditions an electric
conductivity more than an order of magnitude higher than reported previously is
realized. The obtained thermoelectric power-factor at room temperature is
comparable to the state of the art for thermoelectric materials based on earth
abundant, non-toxic elements. The high-throughput screening of extrinsic defects
solves a long standing bottleneck in search of new thermoelectric materials. We
show how the intrinsic carrier concentration in the low-temperature phase of SnSe
is two orders of magnitude higher than in SnS. We furthermore find that the
carrier concentration in SnSe can still be further optimized by silver doping.
PMID- 25115283
TI - Comparative studies using the Morris water maze to assess spatial memory deficits
in two transgenic mouse models of Alzheimer's disease.
AB - Evaluation of the efficacy of novel therapeutics for potential treatment of
Alzheimer's disease (AD) requires an animal model that develops age-related
cognitive deficits reproducibly between independent groups of investigators.
Herein we assessed comparative temporal changes in spatial memory function in two
commercially available transgenic mouse models of AD using the Morris water maze
(MWM), incorporating both visible and hidden platform training. Individual
cohorts of cDNA-based 'line 85'-derived double-transgenic mice coexpressing the
'Swedish' mutation of amyloid precursor protein (APPSwe) and the presenillin 1
(PS1) 'dE9' mutation were assessed in the MWM at mean ages of 3.6, 9.3 and 14.8
months. We found significant deficits in spatial memory retention in
APPSwe/PS1dE9 mice aged 3.6 months and robust deficits in spatial memory
acquisition and retention in APPSwe/PS1dE9 mice aged 9.3 months, with a further
significant decline by age 14.8 months. beta-Amyloid deposits were present in
brain sections by 7.25 months of age. In contrast, MWM studies with individual
cohorts (aged 4-21 months) of single-transgenic genomic-based APPSwe mice
expressing APPSwe on a yeast artificial chromosomal (YAC) construct showed no
significant deficits in spatial memory acquisition until 21 months of age. There
were no significant deficits in spatial memory retention up to 21 months of age
and beta-amyloid deposits were not present in brain sections up to 24 months of
age. These data, generated using comprehensive study designs, show that
APPSwe/PS1dE9 but not APPSwe YAC mice appear to provide a suitably robust model
of AD for efficacy assessment of novel AD treatments in development.
PMID- 25115285
TI - In vivo assessment of the effect of a cream containing Avena Rhealba((r)) extract
and hyaluronic acid on the restoration of the skin barrier in de-epidermised skin
produced with an erbium-YAG laser.
AB - Wound healing studies require standardised methods for evaluating wounding and
skin repair. Our study aimed to demonstrate the suitability of the erbium-YAG (Er
YAG) laser method to produce reliable epidermal lesions for evaluation of
different skin repair creams. Skin de-epidermised by Er-YAG laser (four uniform
epidermal ablations, area 8 * 8mm, in 21 healthy subjects) was treated with a
product (A) containing Avena Rhealba((r)) extract and hyaluronic acid and
assessed for epidermal regeneration and barrier restoration. This treatment was
compared to two reference products (B) and (C) and an untreated control. Over 22
days of treatment, double-blind measurements of wound characteristics were made
for instrumental (wound surface area, barrier restoration, 3D skin topography)
and clinical evaluation (lesion quality and tolerance). Tested product (A)
resulted in a shorter time (9 days) and faster rate of wound closure than product
C (12 days) and the untreated zone (16 days). Results for products (A) and (B)
were similar. Clinical evaluation of lesion quality showed the same trends as the
wound area/closure parameter. Barrier recovery assessments revealed that all
three products showed a similar rate of decreasing Transepidermal Water Loss
(TEWL), which was significantly faster than the rate for the control. In
conclusion, the laser-induced epidermal wound model provided standardised
lesions, enabling discrimination between different topical skin repair products.
PMID- 25115287
TI - Length scaling of carbon nanotube electric and photo diodes down to sub-50 nm.
AB - Carbon nanotubes (CNTs) are promising candidates for future optoelectronics and
logic circuits.1-3 Sub-10 nm channel length CNT transistors have been
demonstrated with superb performance.4 Yet, the scaling of CNT p-n diodes or
photodiodes, basic elements for most optoelectronic devices, is held back on a
scale of micrometers.5-8 Here, we demonstrate that CNT diodes fabricated via a
dopant-free technique show good rectifying characteristics and photovoltaic
response even when the channel length is scaled to sub-50 nm. By making a trade
off between performance and size, a diode with both channel length and contact
width around 100 nm, fabricated on a CNT with a small diameter (d ~ 1.2 nm),
shows a photovoltage of 0.24 V and a fill factor of up to 60%. Study on the
dependence of turn-on voltage on scaled channel length reveals transferred
charges induced potential barrier at the contact in long channel diodes and the
effect of self-adjusting charge distribution. This effect could be utilized for
realizing stable and high performance sub-100 nm pitch CNT diodes. As elementary
building blocks, such tiny electric and photodiodes could be used in nanoscale
rectifiers, photodetectors, light sources, and high-efficiency photovoltaic
devices.
PMID- 25115286
TI - Determinants of outcome of solitary fibrous tumors of the pleura: an
observational cohort study.
AB - BACKGROUND: Solitary fibrous tumors of the pleura (SFTP) are rare and their long
term outcome is difficult to predict, as there are insufficient data which allow
accurate characterization of the malignant variant. Thus the aim of this study
was to describe the outcome and possible determinants of malignant behavior of
SFTPs. METHODS: Data were collected retrospectively from medical records of
patients treated at the University Hospital Zurich from 1992 to 2012. Kaplan
Meier and Cox regression analysis were performed to define disease-free survival
time (defined as survival without tumor-recurrence or tumor-related death) using
the classical histo-morphological criteria (tumor size, localization,
pedunculation, tumor necrosis or hemorrhage, mitotic activity and nuclear
pleomorphism) and immunohistochemical parameters. RESULTS: 42 patients (20 males)
with SFTP (median (IQR) age 62 (56-71) years) could be identified. SFTP were
associated with symptoms in 50% of all cases. Complete resection was achieved by
video-assisted thoracic surgery or thoracotomy in 20 and 22 patients,
respectively. Three SFTP-related deaths (7.1%) and four tumor recurrences (9.5%)
were observed. Mean disease-free survival time was 136.2 (+/- 13.1) months, and 2
, 5- and 10-year disease-free survival was 91%, 84%, and 67%, respectively. Mean
disease-free survival inversely correlated with the mean tumor diameter, number
of mitotic figures and proliferation rate (Ki-67 expression). Other criteria
(tumor necrosis, atypical localization, sessile tumor, and pleomorphism) were not
statistically significant prognostic parameters. CONCLUSIONS: Patients with large
SFTP with a high mitotic index and high proliferation rate should be followed-up
closely and over a prolonged time period in order to recognize recurrence of the
SFTP early and at a treatable stage. Future research on this topic should focus
on the prognostic role of immunohistochemistry including Ki-67 expression and
molecular parameters.
PMID- 25115288
TI - Characterization of 19 new microsatellite loci for the Omani barb Garra
barreimiae from 454 sequences.
AB - BACKGROUND: Garra barreimiae is a cyprinid fish from the southeastern Arabian
Peninsula, which inhabits regularly desiccating wadis and survives in isolated
ponds or underground. In 1984 a cave-dwelling population was found in the Al
Hoota cave system and previous genetic analyses revealed some differentiation
with limited gene flow between the surface populations and the cave population.
Since no suitable markers are available for evaluation of gene flow between the
cave population and the adjacent surface populations, we focused on designing and
establishing novel microsatellite markers from next generation sequencing data.
FINDINGS: 19 microsatellite markers containing di- and tetranucleotide simple
sequence repeats were developed from 454 sequences. Forty-four individuals from
two surface populations (Wadi Al Falahi and Misfat Al Abriyeen) of G. barreimiae
(sampling permission number 13/2012, export permission number 29/2012) were used
for analyses and characterization of the loci. On average, the number of alleles
per locus is 7.6 (range: 2-20). Two markers displayed indication of linkage
disequilibrium in both populations (DL6X, 9XNC). Significant deviation from Hardy
Weinberg equilibrium was observed at four loci in the Misfat Al Abriyeen
population (2PUM, 88CM, 1EHE, 3Z7M) and at two loci in the Wadi Al Falahi
population (QLIM, 3 N43). Three of the microsatellite loci were significant for
null alleles in one of the two populations (Misfat Al Abriyeen: CJHG; Wadi Al
Falahi: PH8A, 3ROZ). Expected and observed heterozygosities ranged from 0 to
95.0% respectively from 0 to 95.8% (Wadi Al Falahi) and from 0 to 89.1%
respectively from 0 to 95.0% (Misfat Al Abriyeen). Fourteen of these markers were
successfully cross-amplified in G. rufa. CONCLUSION: This 19 microsatellite loci
provide a useful tool to understand the structure and genetic differences of
populations. Moreover, these markers will help to evaluate species delimitation
in G. barreimiae and potentially even in related species.
PMID- 25115290
TI - Ethnic Minority Status and Body Image Dissatisfaction: A Scoping Review of the
Child and Adolescent Literature.
AB - To systematically summarize the literature examining ethnic minority status and
body image dissatisfaction (BID) among children and adolescents living in Canada
and the United States. Literature was identified by entering search terms into
six electronic databases and through an electronic hand search of key research
journals. Eligible sources were those published between 1946 and November 2012,
conducted within Canada or the United States, included ethnic minority children
or adolescents (<19 years), and measured BID through self-report. Synthesis of
the sources followed the principles of thematic and content analysis (Vaismoradi
et al. in Nurs Health Sci 15:398-405, 2013). A total of 33 sources were included
in our scoping synthesis; spanning from 1991 to 2011. No results emerged from
Canada. Evidence from the United States is equivocal. The literature is plagued
by inconsistent nomenclature and inadequate attention to issues of measurement,
sex and gender. A more robust evidence-base requires advanced methods to examine
the intersection of ethnicity, sex and gender on BID among children and
adolescents.
PMID- 25115291
TI - The Impact of Healthcare Access on Knowledge and Willingness for HIV Testing in
Chinese Female Entertainment Workers.
AB - Chinese female entertainment workers are at high risk for HIV. We assessed the
impact of healthcare access on HIV knowledge, condom use, and their willingness
to receive HIV testing. We surveyed 257 entertainment workers in a cross
sectional study. Demographic, knowledge, and behavioral risk factors were
examined. Of 257 women, 107 (42.1%) reported inconsistent condom use. Only 9% had
prior HIV testing. Their HIV knowledge was generally poor. Having access to
healthcare, being able to obtain condoms, and managers providing health
information were associated with consistent condom use (all P < 0.01). Having
access to healthcare was related to previous HIV testing (P < 0.01). Our study
showed that having a doctor and access to healthcare had positive effects on HIV
knowledge and likelihood of condom use and previous HIV testing. Chinese medical
providers can play a significant role in encouraging HIV testing and outreach in
migrant women employed at entertainment venues.
PMID- 25115292
TI - Extrusion of the medial meniscus in knee osteoarthritis assessed with a rotating
clino-orthostatic permanent-magnet MRI scanner.
AB - PURPOSE: The objectives of this study were to assess the influence of weight
bearing on tibiofemoral osteoarthritis, including medial meniscal extrusion, by
using a low-field (0.25 T) rotating clino-orthostatic permanent-magnet magnetic
resonance (MR) scanner, and to analyse correlations of medial meniscal extrusion
with the patient's Kellgren-Lawrence score, body mass index, and all the
osteoarthritis features of the WORMS scoring system. MATERIALS AND METHODS:
Twenty-six patients (69.2% women and 30.8% men; mean age 67 +/- 9.7 years) with
medial tibiofemoral knee osteoarthritis were prospectively enrolled and MR
sequences were acquired in both clino- and orthostatic position. MR images were
assessed by two independent radiologists, according to the WORMS scale. Medial
meniscal extrusion was measured and its clino-orthostatic difference (?MME) was
calculated. RESULTS: Intra- and inter-observer agreement of the WORMS Global
Score readings was high by Cohen's K test (>0.81). No significant clino
orthostatic changes in the scoring parameters of the medial tibiofemoral joint
were shown by Wilcoxon's test. Medial meniscal extrusion measured on orthostatic
images was significantly higher than that measured in clinostatic position (p <
0.0001). At univariate analysis, the Kellgren-Lawrence score, WORMS Global Score,
cartilage loss, meniscal damage, and osteophytes were significantly correlated to
?MME (p < 0.005). Using a multiple regression model, tibiofemoral cartilage loss
was found to correlate independently with ?MME (p = 0.0499). CONCLUSIONS: Medial
meniscal extrusion, evaluated with an open-configuration, rotating MR scanner,
increased from the clinostatic to the orthostatic position. ?MME, a new meniscal
parameter, correlated with several important features of medial tibiofemoral
osteoarthritis.
PMID- 25115289
TI - Seeing the forests and the trees--innovative approaches to exploring
heterogeneity in systematic reviews of complex interventions to enhance health
system decision-making: a protocol.
AB - BACKGROUND: To improve quality of care and patient outcomes, health system
decision-makers need to identify and implement effective interventions. An
increasing number of systematic reviews document the effects of quality
improvement programs to assist decision-makers in developing new initiatives.
However, limitations in the reporting of primary studies and current meta
analysis methods (including approaches for exploring heterogeneity) reduce the
utility of existing syntheses for health system decision-makers. This study will
explore the role of innovative meta-analysis approaches and the added value of
enriched and updated data for increasing the utility of systematic reviews of
complex interventions. METHODS/DESIGN: We will use the dataset from our recent
systematic review of 142 randomized trials of diabetes quality improvement
programs to evaluate novel approaches for exploring heterogeneity. These will
include exploratory methods, such as multivariate meta-regression analyses and
all-subsets combinatorial meta-analysis. We will then update our systematic
review to include new trials and enrich the dataset by surveying authors of all
included trials. In doing so, we will explore the impact of variables not,
reported in previous publications, such as details of study context, on the
effectiveness of the intervention. We will use innovative analytical methods on
the enriched and updated dataset to identify key success factors in the
implementation of quality improvement interventions for diabetes. Decision-makers
will be involved throughout to help identify and prioritize variables to be
explored and to aid in the interpretation and dissemination of results.
DISCUSSION: This study will inform future systematic reviews of complex
interventions and describe the value of enriching and updating data for exploring
heterogeneity in meta-analysis. It will also result in an updated comprehensive
systematic review of diabetes quality improvement interventions that will be
useful to health system decision-makers in developing interventions to improve
outcomes for people with diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
registration no. CRD42013005165.
PMID- 25115293
TI - Nuclear medicine and the emergency department patient: an illustrative case-based
approach.
AB - Radiologists are familiar with the use of radiographs, computed tomography,
magnetic resonance imaging and ultrasound in the acute clinical setting. However,
there are some specific clinical scenarios which may be found in nuclear medicine
imaging problem-solving tools. These clinical scenarios and imaging techniques
are less frequent, and the referring clinician from the emergency department may
not consider these alternatives. It is important for the radiologist to be aware
of these techniques to be able to guide the clinician to use those tools, which
may result in optimal patient care. In this article, we will discuss those
nuclear medicine studies which have application in the setting of an emergency
radiology practice.
PMID- 25115294
TI - Diaphragmatic injuries: why do we struggle to detect them?
AB - Diaphragmatic injury is an uncommon traumatic condition. It can be easily missed
due to a lack of awareness by both clinicians and radiologists. A high index of
suspicion is required for the establishment of an early diagnosis and prevention
of life-threatening complications. Multidetector computed tomography (MDCT) is
the modality of choice for the detection of diaphragmatic injury. In this review
article, we illustrate the MDCT appearance of blunt and penetrating diaphragmatic
injuries and emphasize the role of the emergency radiologist in detecting these
entities.
PMID- 25115296
TI - Our experience with retroperitoneal laparoendoscopic single-site
ureterolithotomy.
AB - AIM: To report our experience with retroperitoneal laparoendoscopic single-site
(LESS) ureterolithotomy for the management of large proximal ureteral stones.
PATIENTS AND METHODS: From July 2011 to April 2012, 20 patients underwent
retroperitoneal LESS ureterolithotomy. The indications for the operation were
impacted upper ureteral stones larger than 15 mm. A reusable elastic single-port
device with 3 working channels was inserted through the 2.5-cm incision at the
midpoint between the costal arch and iliac crest on the mid-axillary line. A
rigid 10-mm 30 degrees extra-long laparoscope was introduced for monitoring, and
a combination of lengthened pre-bent and conventional laparoscopic instruments
was used for handling. The surgical procedure was similar to conventional
retroperitoneal laparoscopic ureterolithotomy. RESULTS: Retroperitoneal LESS
ureterolithotomy was completed in all of the patients. The mean stone size was
18.8 mm (range 16-28). The mean operative time was 108 min (range 75-140).
Significant bleeding was not observed, and no major intraoperative complications
occurred in any of the patients. The mean hospital stay was 4.4 days (range 3-7).
CONCLUSIONS: Retroperitoneal LESS ureterolithotomy, using a reusable elastic
single-port device, is technically feasible and safe, and the combination of
conventional and pre-bent laparoscopic instruments represents an attractive
option for retroperitoneal LESS.
PMID- 25115297
TI - Soluble CD138/Syndecan-1 Increases in the Sera of Patients with Moderately
Differentiated Bladder Cancer.
AB - BACKGROUND: CD138/Syndecan-1 (Sdc-1) is expressed on the tumor and stromal cells
of invasive bladder carcinoma. CD138/Sdc-1 shedding from the cell surface is
associated with the invasive phenotype in lung and breast cancers. PATIENTS AND
METHODS: Soluble CD138/Sdc-1 was measured in the sera of 86 bladder cancer
patients and 57 healthy individuals by a commercial ELISA assay. RESULTS: Soluble
Sdc-1 was increased in the sera of patients with bladder cancer (138.42 +/- 81.85
vs. 86.48 +/- 82.58 ng/ml, p = 0.0003). Patients aged over 70 years had higher
levels of CD138/Sdc-1 in their sera (159.7 +/- 15.77 vs. 124.5 +/- 9.99 ng/ml, p
= 0.025), and soluble Sdc-1 levels were higher in the sera of patients with
moderately differentiated tumors compared to poorly differentiated ones (170.47
+/- 85.06 vs. 101.79 +/- 68.24 ng/ml, p = 0.01). The soluble Sdc-1 level was
higher in muscle-invasive (154.45 +/- 83.60 vs. 89.9 +/- 55.02 ng/ml) but not
lymphatic-invasive (106.25 +/- 52.10 vs. 123.43 +/- 63.76 ng/ml) tumors (p =
0.027 and 0.45, respectively). A non-significant trend of soluble Sdc-1 increase
in the sera of male patients compared to female patients was observed (145.38 +/-
85.47 vs. 110.20 +/- 59.04 ng/ml, p = 0.054). CONCLUSION: The elevated levels of
soluble CD138/Sdc-1 in older bladder cancer patients and those with muscular
invasion sheds some light on the mechanisms of the disease invasion.
PMID- 25115298
TI - EFA6B antagonizes breast cancer.
AB - One of the earliest events in epithelial carcinogenesis is the dissolution of
tight junctions and cell polarity signals that are essential for normal
epithelial barrier function. Here, we report that EFA6B, a guanine nucleotide
exchange factor for the Ras superfamily protein Arf6 that helps assemble and
stabilize tight junction, is required to maintain apico-basal cell polarity and
mesenchymal phenotypes in mammary epithelial cells. In organotypic three
dimensional cell cultures, endogenous levels of EFA6B were critical to determine
epithelial-mesenchymal status. EFA6B downregulation correlated with a mesenchymal
phenotype and ectopic expression of EFA6B hampered TGFbeta-induced epithelial-to
mesenchymal transition (EMT). Transcriptomic and immunohistochemical analyses of
human breast tumors revealed that the reduced expression of EFA6B was associated
with loss of tight junction components and with increased signatures of EMT,
cancer stemness, and poor prognosis. Accordingly, tumors with low levels of EFA6B
were enriched in the aggressive triple-negative and claudin-low breast cancer
subtypes. Our results identify EFA6B as a novel antagonist in breast cancer and
they point to its regulatory and signaling pathways as rational therapeutic
targets in aggressive forms of this disease.
PMID- 25115299
TI - GBV-C infection and risk of NHL among U.S. adults.
AB - Some retrospective studies suggest an association between infection with GB virus
C (GBV-C) and non-Hodgkin lymphoma (NHL). We evaluated this association
prospectively in a nested case-control study within the U.S. Prostate, Lung,
Colorectal and Ovarian (PLCO) Cancer Screening Trial. Cases (N = 658) and
controls (N = 1,316) were individually matched by age, sex, race/ethnicity,
timing of study entry, and sample selection. Prediagnostic PLCO serum samples
were tested for GBV-C RNA (as a measure of active infection) and E2 antibody
(active or resolved infection). Logistic regression was used to estimate odds
ratios (OR) for the association between GBV-C and NHL overall and NHL subtypes.
Twelve cases (1.8%) and seven controls (0.5%) were GBV-C RNA-positive. GBV-C RNA
positivity was associated with NHL overall [OR, 3.43; 95% confidence interval
(CI), 1.35-8.71] and, based on small numbers, diffuse large B-cell lymphoma (OR,
5.31; 95% CI, 1.54-18.36). The association with NHL persisted when the interval
between testing and selection was greater than 4 years (OR, 6.00; 95% CI, 1.21
29.73). In contrast, E2 antibody positivity was not associated with NHL risk (OR,
1.08; 95% CI, 0.74-1.58). Our study demonstrates that GBV-C infection precedes
development of NHL. GBV-C infection may play an etiologic role in a small
proportion of NHL cases, perhaps by causing chronic immune stimulation or
impaired immunosurveillance.
PMID- 25115295
TI - Bowel intussusceptions in adults: the role of imaging.
AB - Intestinal intussusception in adults is a rare condition, accounting for about
0.003-0.02% of all hospital admissions. This condition in adults represents only
5% of all cases of intussusceptions and is different from paediatric
intussusception, which is usually idiopathic. In contrast, almost 90% of cases in
adults are secondary to various pathologies that serve as a lead point, such as
polyps, Meckel's diverticulum, colonic diverticulum, or malignant or benign
neoplasm. The aim of the present study was to assess the capabilities of
multislice computed tomography (MSCT) in the diagnosis and correct
characterisation of intussusception, especially in distinguishing between
intussusceptions with a lead point and those without. Indeed, although the MSCT
findings that help to differentiate between lead point and non-lead point
intussusceptions have not been well studied, abdominal MSCT remains the most
sensitive radiological tool to confirm bowel intussusceptions. Moreover,
differentiating intussusceptions with a lead point condition from those without
is crucial for directing the patient towards the most appropriate treatment,
avoiding surgery when not necessary.
PMID- 25115302
TI - Defining "serious illness".
PMID- 25115301
TI - Gangliosides drive the tumor infiltration and function of myeloid-derived
suppressor cells.
AB - Although it is now widely appreciated that antitumor immunity is critical to
impede tumor growth and progression, there remain significant gaps in knowledge
about the mechanisms used by tumors to escape immune control. In tumor cells, we
hypothesized that one mechanism of immune escape used by tumors involves the
synthesis and extracellular shedding of gangliosides, a class of biologically
active cell surface glycosphingolipids with known immunosuppressive properties.
In this study, we report that tumor cells engineered to be ganglioside deficient
exhibit impaired tumorigenicity, supporting a link between ganglioside-dependent
immune escape and tumor outgrowth. Notably, we documented a dramatic reduction in
the numbers and function of tumor-infiltrating myeloid-derived suppressor cells
(MDSC) in ganglioside-deficient tumors, in contrast with the large MDSC
infiltrates seen in ganglioside-rich littermate control tumors. Transient
ganglioside reconstitution of the tumor cell inoculum was sufficient to increase
MDSC infiltration, supporting a direct connection between ganglioside production
by tumor cells and the recruitment of immunosuppressive MDSC into the tumor
microenvironment. Our results reveal a novel mechanism of immune escape that
supports tumor growth, with broad implications given that many human tumors
produce and shed high levels of gangliosides.
PMID- 25115300
TI - BRG1/SMARCA4 inactivation promotes non-small cell lung cancer aggressiveness by
altering chromatin organization.
AB - SWI/SNF chromatin remodeling complexes regulate critical cellular processes,
including cell-cycle control, programmed cell death, differentiation, genomic
instability, and DNA repair. Inactivation of this class of chromatin remodeling
complex has been associated with a variety of malignancies, including lung,
ovarian, renal, liver, and pediatric cancers. In particular, approximately 10% of
primary human lung non-small cell lung cancers (NSCLC) display attenuations in
the BRG1 ATPase, a core factor in SWI/SNF complexes. To evaluate the role of BRG1
attenuation in NSCLC development, we examined the effect of BRG1 silencing in
primary and established human NSCLC cells. BRG1 loss altered cellular morphology
and increased tumorigenic potential. Gene expression analyses showed reduced
expression of genes known to be associated with progression of human NSCLC. We
demonstrated that BRG1 losses in NSCLC cells were associated with variations in
chromatin structure, including differences in nucleosome positioning and
occupancy surrounding transcriptional start sites of disease-relevant genes. Our
results offer direct evidence that BRG1 attenuation contributes to NSCLC
aggressiveness by altering nucleosome positioning at a wide range of genes,
including key cancer-associated genes.
PMID- 25115303
TI - Drug resistance is conferred on the model yeast Saccharomyces cerevisiae by
expression of full-length melanoma-associated human ATP-binding cassette
transporter ABCB5.
AB - ABCB5, an ATP-binding cassette (ABC) transporter, is highly expressed in melanoma
cells, and may contribute to the extreme resistance of melanomas to chemotherapy
by efflux of anti-cancer drugs. Our goal was to determine whether we could
functionally express human ABCB5 in the model yeast Saccharomyces cerevisiae, in
order to demonstrate an efflux function for ABCB5 in the absence of background
pump activity from other human transporters. Heterologous expression would also
facilitate drug discovery for this important target. DNAs encoding ABCB5
sequences were cloned into the chromosomal PDR5 locus of a S. cerevisiae strain
in which seven endogenous ABC transporters have been deleted. Protein expression
in the yeast cells was monitored by immunodetection using both a specific anti
ABCB5 antibody and a cross-reactive anti-ABCB1 antibody. ABCB5 function in
recombinant yeast cells was measured by determining whether the cells possessed
increased resistance to known pump substrates, compared to the host yeast strain,
in assays of yeast growth. Three ABCB5 constructs were made in yeast. One was
derived from the ABCB5-beta mRNA, which is highly expressed in human tissues but
is a truncation of a canonical full-size ABC transporter. Two constructs
contained full-length ABCB5 sequences: either a native sequence from cDNA or a
synthetic sequence codon-harmonized for S. cerevisiae. Expression of all three
constructs in yeast was confirmed by immunodetection. Expression of the codon
harmonized full-length ABCB5 DNA conferred increased resistance, relative to the
host yeast strain, to the putative substrates rhodamine 123, daunorubicin,
tetramethylrhodamine, FK506, or clorgyline. We conclude that full-length ABCB5
can be functionally expressed in S. cerevisiae and confers drug resistance.
PMID- 25115304
TI - Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in
metastatic colorectal cancer: a meta-analysis of randomized, controlled trials.
AB - BACKGROUND: Monoclonal antibodies (mAbs) targeting the epidermal growth factor
receptor (EGFR) prolong survival in metastatic colorectal cancer (mCRC) Kirsten
rat sarcoma viral oncogene (KRAS) exon 2 wild-type tumors. Recent evidence has
suggested that other RAS mutations (in exons 3 and 4 of KRAS and exons 2, 3 and 4
of a related gene, NRAS) may also be predictive of resistance. METHODS:
Systematic review and meta-analysis of randomized, controlled trials (RCTs)
evaluating anti-EGFR mAbs that have assessed tumors for new RAS mutations. Tumors
with the new RAS mutations were compared with both tumors without any RAS
mutations and tumors with KRAS exon 2 mutations with respect to anti-EGFR
treatment progression-free survival (PFS) and overall survival (OS) benefit.
RESULTS: Nine RCTs comprising a total of 5948 participants evaluated for both
KRAS exon 2 and new RAS mutations met the inclusion criteria. Approximately 20%
of KRAS exon 2 wild-type tumors harbored one of the new RAS mutations. Tumors
without any RAS mutations (either KRAS exon 2 or new RAS mutations) were found to
have significantly superior anti-EGFR mAb PFS (P < 0.001) and OS (P = 0.008)
treatment effect compared with tumors with any of the new RAS mutations. No
difference in PFS or OS benefit was evident between tumors with KRAS exon 2
mutations and tumors with the new RAS mutations. Results were consistent between
different anti-EGFR agents, lines of therapy and chemotherapy partners. Anti-EGFR
mAb therapy significantly improved both PFS {hazard ratio 0.62 [95% confidence
interval (CI) 0.50-0.76]} and OS [hazard ratio 0.87 (95% CI 0.77-0.99)] for
tumors without any RAS mutations. No PFS or OS benefit was evident with use of
anti-EGFR mAbs for tumors harboring any RAS mutation (P > 0.05). CONCLUSION:
Tumors harboring one of the new RAS mutations are unlikely to significantly
benefit from anti-EGFR mAb therapy in mCRC.
PMID- 25115305
TI - Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines
for diagnosis, treatment and follow-up.
PMID- 25115306
TI - Effectiveness of 3 T PROPELLER DUO diffusion-weighted MRI in differentiating
sinonasal lymphomas and carcinomas.
AB - AIM: To evaluate the value of 3 T Periodically rotated overlapping parallel lines
with enhanced reconstruction (PROPELLER) DUO diffusion-weighted MRI (DW-MRI) in
differentiating sinonasal lymphomas from carcinomas. MATERIALS AND METHODS:
PROPELLER DUO DW-MRI was performed in 23 patients with sinonasal lymphomas and 28
patients with carcinomas histologically confirmed at 3 T MRI. Apparent diffusion
coefficients (ADCs) were obtained with two different b-values (b = 0 and 700
s/mm(2), b = 0 and 1000 s/mm(2)) and two different regions of interest (ROIs)
sampling strategies [whole section (WS), partial section (PS)], respectively.
Difference in ADCs between sinonasal lymphomas and carcinomas was evaluated using
the independent samples t-test or Mann-Whitney U-test. The utility of ADC
thresholds for discriminating between them was evaluated by receiver operating
characteristic analysis. RESULTS: ADCs of sinonasal lymphomas (WS ADCb0,700,
0.838 * 10(-3) mm(2)/s) were significantly (p < 0.001) lower than those of
carcinomas (WS ADCb0,700, 1.396 * 10(-3) mm(2)/s). Using a WS ADC b0,700 value of
1.040 * 10(-3) mm(2)/s as the threshold value effectively differentiated
sinonasal lymphomas from carcinomas with 100% sensitivity, 82.1% specificity, and
82.1% positive and 100% negative predictive values and 90.2% accuracy (b = 0, 700
s/mm(2)). There was no significant difference in diagnostic ability between
different b-values settings (p > 0.05) and different sampling strategies of ROIs
(p > 0.05), respectively. Additionally, there was significant differences in the
ADCs between diffuse large B-cell lymphomas and natural killer (NK)/T-cell
lymphomas (p < 0.05). CONCLUSION: PROPELLER DUO DW-MRI can effectively
differentiate sinonasal lymphomas from carcinomas.
PMID- 25115307
TI - Re: Are radiologists the contemporary anatomists?
PMID- 25115310
TI - Revealing the substrate origin of the linear dispersion of silicene/Ag(111).
AB - The band structure of the recently synthesized (3 * 3) silicene monolayer on (4 *
4) Ag(111) is investigated using density functional theory. A k-projection
technique that includes the k?-dependence of the surface bands is used to
separate the contributions arising from the silicene and the substrate, allowing
a consistent comparison between the calculations and the angle-resolved
photoemission experiments. Our calculations not only reproduce the observed gap
and linear dispersion across the K point of (1 * 1) silicene but also demonstrate
that these originate from the k?-dependence of Ag(111) substrate states (modified
by interactions with the silicene) and not from a Dirac state.
PMID- 25115309
TI - Pharmacological actions of thymol and an analogue at GABAB autoreceptors.
AB - GABAB autoreceptors inhibit release of GABA from GABAergic nerve terminals.
Agonists of these receptors (e.g. baclofen) inhibit, whereas antagonists (e.g.
(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; Sch 50911) enhance release of the
transmitter. The actions of thymol (2-isopropyl-5-methylphenol) and the
structurally related compound 2-tert-butyl-4-methylphenol, (4MP) on the release
of [(3) H]-GABA were examined in rat neocortical slices where the GABAergic
nerves had been preloaded with [(3) H]-GABA and subsequently stimulated
electrically on two occasions (S1 and S2 ). Test agents, baclofen and Sch 50911
were added to the superfusion medium prior to the second period of stimulation
(S2 ). Stimulation-induced overflow (SIO) of [(3) H]-GABA as a consequence of
these stimulations (SIO1 and SIO2 ) were calculated and the effects of agents
determined by comparing the SIO2 /SIO1 ratio in the presence of each agent with
that in control tissue. Thymol potentiated the release of [(3) H]-GABA (EC50 170
MUmol/L), an action reversed by baclofen (2 MUmol/L). Baclofen alone had little
effect on GABA release. Release of [(3) H]-GABA was inhibited by 4MP (IC50 3
MUmol/L) and this effect was blocked by Sch 50911 (10 MUmol/L). Alone, Sch 50911
markedly potentiated the release of GABA. These results imply that 4MP is an
agonist of GABAB autoreceptors; however, further studies are needed to confirm
that thymol is indeed a GABAB autoreceptor antagonist. Of interest are structural
differences in these agents. Thymol has a propyl group in the ortho position
relative to the phenolic hydroxyl, whereas in 4MP this is a butyl group and the
methyl group moves from position 5 to 4. Whether one or both of these changes was
responsible for the above actions is unknown.
PMID- 25115308
TI - Neck-specific training with a cognitive behavioural approach compared with
prescribed physical activity in patients with cervical radiculopathy: a protocol
of a prospective randomised clinical trial.
AB - BACKGROUND: Patients with cervical radiculopathy often have neck- and arm pain,
neurological changes, activity limitations and difficulties in returning to work.
Most patients are not candidates for surgery but are often treated with different
conservative approaches and may be sick-listed for long periods. The purpose of
the current study is to compare the effectiveness of neck-specific training
versus prescribed physical activity. METHODS/DESIGN: The current protocol is a
two armed intervention randomised clinical trial comparing the outcomes of
patients receiving neck specific training or prescribed physical activity. A
total of 144 patients with cervical radiculopathy will be randomly allocated to
either of the two interventions. The interventions will be delivered by
experienced physiotherapists and last 14 weeks. The primary outcome variable is
neck- and arm pain intensity measured with a Visual Analogue Scale accompanied
with secondary outcome measures of impairments and subjective health measurements
collected before intervention and at 3, 6, 12 and 24 months after base-line
assessment. DISCUSSION: We anticipate that the results of this study will provide
evidence to support recommendations as to the effectiveness of conservative
interventions for patients with cervical radiculopathy. TRIAL REGISTRATION:
ClinicalTrials.gov identifier: NCT01831271.
PMID- 25115311
TI - Educational intervention to improve the health outcomes of children with sickle
cell disease.
AB - INTRODUCTION: Although sickle cell disease (SCD) is the most common single gene
disorder worldwide, caregivers of children do not have adequate knowledge about
the illness and its management. The purpose of this study was to assess the
efficacy of education along with tailored written materials in changing the
behaviors of caregivers to help them provide better care for children with SCD.
METHODS: A preintervention and postintervention quasi-experimental design was
used. A convenience sample of 43 caregivers of 57 children were asked to complete
a questionnaire related to their knowledge of SCD before and after educational
sessions. The educational sessions (the intervention) were provided to caregivers
at the Children's Cancer Center in Lebanon by one registered nurse, one certified
pediatric nurse practitioner, and one pediatric hematologist. Emergency
department (ED) visits and hospitalizations were compared 2 months before and 2
months after the intervention. RESULTS: A statistically significant increase was
found in the knowledge of caregivers about the cause, symptoms, and management of
the disease. A statistically significant decrease occurred in the number of
hospitalizations before and after the intervention but not in the number of
visits to the ED. Multiple regression analysis found that none of the background
variables were related to knowledge, ED visits, or hospitalizations. CLINICAL
IMPLICATIONS: Education and written materials written in a simple language that
is understood by 5th-graders were beneficial in improving the knowledge of
caregivers and in decreasing the number of hospitalizations of children with SCD.
PMID- 25115312
TI - Adolescent with Fever, hypotension, and respiratory distress.
PMID- 25115313
TI - Role of near-infrared fluorescence imaging in head and neck cancer surgery: from
animal models to humans.
AB - Complete resection of head and neck cancers with negative surgical margins
improves the prognosis of the disease and decreases the recurrence rate. Near
infrared fluorescence-guided surgery of head and neck cancer is a rapidly
evolving field that represents an invaluable tool for tumor detection and
resection. Here, we present a literature review of the principles of near
infrared fluorescence imaging and its use in head and neck cancer surgery. We
discuss important studies in both animal models and humans that have been carried
out up to this point. We also outline the important fluorescent molecules and
devices used in head and neck fluorescence imaging-guided surgery. Although near
infrared fluorescence-guided surgery for head and neck cancers showed efficacy in
animal models, its use in humans is limited by the small number of fluorescent
probes that are approved for clinical use. However, it is considered as a novel
surgical aid that helps delineate tumor margins preoperatively and could spare
patients from the added morbidity that is associated with additional surgery or
chemoradiation. In addition, it is a useful tool to detect sentinel lymph nodes
as well as metastatic lymph nodes.
PMID- 25115314
TI - Association between sudden sensorineural hearing loss and anxiety disorder: a
population-based study.
AB - Anxiety disorder (AD) is commonly associated with a number of physical illnesses.
No previous study has investigated the association between AD and sudden
sensorineural hearing loss (SSNHL). In this study, we investigated the
association between prior AD and SSNHL using a population-based dataset in
Taiwan. Sampled subjects of this case-control study were retrieved from the
Taiwan "Longitudinal Health Insurance Database". We identified 3,522 patients who
had a diagnosis of SSNHL as cases and 10,566 age- and gender-matched subjects
without SSNHL as controls. A conditional logistic regression was used to
calculate the odds ratio (OR) for having previously been diagnosed with AD
between cases and controls. We found that of 14,088 patients, 13.4% had a prior
AD diagnosis, 17.8 and 11.9% for the SSNHL group and controls, respectively.
After adjusting for patient socioeconomic characteristics and comorbid medical
disorders, SSNHL patients were more likely to have prior AD than the controls (OR
1.49, 95% confidence interval (CI) 1.34-1.66, p < 0.001). Furthermore, we found
that the significant relationship between SSNHL and prior AD decreased with age.
The relationship was the most pronounced among those aged <=44 years, with an
adjusted OR of 1.86 (95% CI 1.48-2.33, p < 0.001) for cases compared to controls.
We concluded that patients with SSNHL had a higher proportion of prior AD than
non-SSNHL-diagnosed controls. Further study is needed to confirm our findings and
explore the underlying pathomechanisms.
PMID- 25115315
TI - Orbital compartment: effects of emergent canthotomy and cantholysis.
AB - The objective of this study was to determine the effect of orbital decompression
procedures on the intraocular pressure (IOP). The orbital compartment syndrome
represents an emergency situation. Due to the elevated IOP vision loss may ensue.
Several maneuvers including lateral canthotomy are discussed to reduce the IOP.
Eight orbits were studied in a fresh frozen cadaveric model (4 specimens).
Intraorbital volume was determined by CT volumetry. An orbital compartment
syndrome was simulated by injecting viscous material into the orbit. Injected
volumes were documented and lateral canthotomy, cantholysis, inferior and
superior septolysis were performed. IOP and exophthalmometric measurements were
obtained after each intervention. Controlled elevation of IOP was achieved in all
specimens. IOP was partially reduced after performing a lateral canthotomy in
eight orbits. IOP was significantly and sufficiently decreased under 20 mmHg by
inferior cantholysis in seven orbits. An additional superior cantholysis was
necessary in two orbits to achieve a complete decompression. Inferior or superior
septolysis were not needed to further reduce the IOP. Lateral canthotomy must be
followed by an inferior cantholysis to successfully decompress an orbital
compartment syndrome in the majority of cases. Occasionally, superior cantholysis
may generate additional benefit. Additional inferior and superior septolysis were
not shown to provide a beneficial effect when performed after canthotomy and
cantholysis.
PMID- 25115317
TI - Early dermoscopic detection of lentigo maligna within a lesion of pigmented
contact dermatitis.
PMID- 25115316
TI - Steroids and antihistamines synergize to inhibit rat's airway smooth muscle
contractility.
AB - Both glucocorticoids and H1-antihistamines were widely used on patients with
allergic rhinitis (AR) and obstructive airway diseases. However, their direct
effects on airway smooth muscle were not fully explored. In this study, we tested
the effectiveness of prednisolone (Kidsolone) and levocetirizine (Xyzal) on
isolated rat trachea submersed in Kreb's solution in a muscle bath. Changes in
tracheal contractility in response to the application of parasympathetic mimetic
agents were measured. The following assessments of the drug were performed: (1)
effect on tracheal smooth muscle resting tension; (2) effect on contraction
caused by 10(-6) M methacholine; (3) effect of the drug on electrical field
stimulation (EFS) induced tracheal smooth muscle contractions. The result
revealed sole use of Kidsolone or Xyzal elicited no significant effect or only a
little relaxation response on tracheal tension after methacholine treatment. The
tension was 90.5 +/- 7.5 and 99.5 +/- 0.8 % at 10(-4) M for Xyzal and 10(-5) M
for Kidsolone, respectively. However, a dramatically spasmolytic effect was
observed after co-administration of Kidsolone and Xyzal and the tension dropped
to 67.5 +/- 13.6 %, with statistical significance (p < 0.05). As for EFS-induced
contractions, Kidsolone had no direct effect but Xyzal could inhibit it, with
increasing basal tension. In conclusion, using glucocorticoids alone had no
spasmolytic effect but they can be synergized with antihistamines to dramatically
relax the trachea smooth muscle within minutes. Therefore, for AR patients with
acute asthma attack, combined use of those two drugs is recommended.
PMID- 25115318
TI - Substance abuse-specific knowledge transfer or loss? Treatment program turnover
versus professional turnover among substance abuse clinicians.
AB - This longitudinal study investigated the extent to which substance abuse (SA)
clinician turnover is associated with SA-specific knowledge loss due to change in
professions (professional turnover) versus SA-specific knowledge transfer due to
movement from one SA clinical setting to another (treatment program turnover).
For this study, clinicians had to have voluntarily left their current treatment
program. Eligible clinicians completed a quantitative survey while employed and a
qualitative post-employment exit interview 1 year later. Compared to those that
exited the SA profession (n = 99), clinicians who changed treatment programs (n =
120) had greater SA-specific formal knowledge and were more likely to be
personally in recovery. No differences were found between the two groups in terms
of SA-specific practical knowledge.
PMID- 25115320
TI - Response to chemotherapy, reexposure to crizotinib and treatment with a novel ALK
inhibitor in a patient with acquired crizotinib resistance.
AB - The treatment of advanced non-small cell lung cancer (NSCLC) has dramatically
changed over the last decade. It has developed from an unspecific approach based
on platinum doublet chemotherapy to a personalized, molecularly targeted therapy.
Crizotinib is a new tyrosine kinase inhibitor approved for the treatment of NSCLC
with gene rearrangement of EML4 and ALK. Despite good initial responses, patients
treated with crizotinib relapse after an average of 10 months. In this case
report, we present a patient with acquired crizotinib resistance whose
adenocarcinoma responded to a second course of crizotinib following a drug
holiday and chemotherapy with pemetrexed. This is the second case report to
suggest that retreatment with crizotinib is an option for patients with initial
benefit from ALK inhibition.
PMID- 25115319
TI - Pregnancy outcomes and birth defects from an antiretroviral drug safety study of
women in South Africa and Zambia.
AB - OBJECTIVE: To evaluate the safety of combination antiretroviral therapy (ART) in
conception and pregnancy in different health systems. DESIGN: A pilot ART
registry to measure the prevalence of birth defects and adverse pregnancy
outcomes in South Africa and Zambia. METHODS: HIV-infected pregnant women on ART
prior to conception were enrolled until delivery, and their infants were followed
until 1 year old. RESULTS: Between October 2010 and April 2011, 600 women were
enrolled. The median CD4 cell count at study enrollment was lower in South Africa
than Zambia (320 vs. 430 cells/MUl; P < 0.01). The most common antiretroviral
drugs at the time of conception included stavudine, lamivudine, and nevirapine.
There were 16 abortions (2.7%), one ectopic pregnancy (0.2%), 12 (2.0%)
stillbirths, and 571 (95.2%) live infants. Deliveries were more often preterm
(29.7 vs. 18.4%; P = 0.01) and the infants had lower birth weights (2900 vs. 2995
g; P = 0.11) in Zambia compared to South Africa. Thirty-six infants had birth
defects: 13 major and 23 minor. There were more major anomalies detected in South
Africa and more minor ones in Zambia. No neonatal deaths were attributed to
congenital birth defects. CONCLUSIONS: An Africa-specific, multi-site
antiretroviral drug safety registry for pregnant women is feasible. Different
prevalence for preterm delivery, delivery mode, and birth defect types between
women on preconception ART in South Africa and Zambia highlight the potential
impact of health systems on pregnancy outcomes. As countries establish ART drug
safety registries, documenting health facility limitations may be as essential as
the specific ART details.
PMID- 25115321
TI - Long-term psychosocial impact of otoplasty performed on children with prominent
ears.
AB - OBJECTIVES: To investigate the psychosocial impact of prominent ears on children,
and evaluate the outcomes of otoplasty two years after surgery, using the Child
Behavior Checklist to comparatively evaluate patients' psychosocial profiles.
METHOD AND RESULTS: A total of 198 otoplasty procedures were performed in 107
patients (85 per cent bilateral procedures). Otoplasty was performed solely in 86
patients and concurrently with other procedures in 21 patients. All children who
underwent surgery obtained good post-operative results, with satisfactory
correction of the deformity reported by the patients and their parents or
guardians. There were statistically significant decreases in Child Behavior
Checklist scores in the domains of: anxiety and depression (p = 0.028), social
problems (p = 0.018), difficulties in thinking (p = 0.012), total behavioural
problems (p = 0.012), internalising problems (p = 0.020) and externalising
problems (p = 0.044), and near-significant decreases in scores for attention
problems (p = 0.055) and aggressive behaviour (p = 0.078). There was a
statistically significant increase in the score for total social competence (p =
0.031). CONCLUSION: Psychological problems associated with anatomical deformities
such as prominent ears can be reduced by means of appropriate corrective surgery.
Psychological support is necessary for the patient.
PMID- 25115322
TI - Magnetic resonance imaging in lumbar gunshot wounds: an absolute
contraindication?
AB - OBJECT: Performance of MR imaging in patients with gunshot wounds at or near the
lumbar spinal canal is controversial. The authors reviewed the literature on the
use of MR imaging in gunshot wounds to the spine. They discuss the results from
in vitro and clinical studies, analyze the physical properties of common
projectiles, and evaluate the safety and indications for MR imaging when metallic
fragments are located near the spinal canal. METHODS: A review of the English
language literature was performed. Data from 25 articles were analyzed, including
5 in vitro studies of the interaction between 95 projectiles and the MR system's
magnetic fields, and the clinical outcomes in 22 patients with metallic fragments
at or near the spinal canal who underwent MR imaging. RESULTS: Properties of 95
civilian and military projectiles were analyzed at a magnet strength of 1, 1.5,
3, and 7 T. The most common projectiles were bullets with a core of lead, either
with a copper jacket or unjacketed (73 [76.8%] of 95). Steel-containing (core or
jacket) projectiles comprised 14.7%. No field interaction was evident in 78
(96.3%) of the 81 nonsteel projectiles. All steel projectiles showed at least
positive deflection forces, longitudinal migration, or rotation. Heating of the
projectiles was clinically insignificant. Image artifact was significant in all 9
steel bullets tested, but was not significant in 39 (88.6%) of the 44 nonsteel
bullets tested. Overall, 22 patients with complete (82%) and incomplete (14%)
spinal cord injury secondary to a projectile lodged inside the spinal canal
underwent MR imaging. Discomfort and further physical or neurological deficits
were not reported by any patient. Two patients with spinal cord injuries
underwent MR imaging studies before surgical decompression and had subsequent,
significant neurological improvement. CONCLUSIONS: Metallic implants near or at
the spinal canal are a relative contraindication for MR imaging. However, safe MR
imaging might be feasible when a projectile's properties and a patient's
individualized clinical presentation are considered.
PMID- 25115323
TI - The association between bullying-related behaviours and subjective health
complaints in late adolescence: cross-sectional study in Greece.
AB - BACKGROUND: Bullying is quite prevalent in the school setting and has been
associated with several subjective health complaints such as headache, backache,
abdominal pain, dizziness, fatigue and sleep problems. The aim of the present
study was to investigate the association between bullying and subjective health
complaints in a sample of Greek adolescents taking into account the presence of
psychiatric morbidity. METHODS: A stratified random sample of 2427 adolescents
aged 16-18 years old and attending senior high schools were randomly selected for
a computerized interview. Subjective health complaints were assessed using a
symptom checklist used in the context of a previous World Health Organization
study and relevant sections of the revised Clinical Interview Schedule (CIS-R).
The latter was also used for the assessment of psychiatric morbidity. Bullying
was assessed with the revised Olweus bully/victim questionnaire. A series of
logistic regression models were used to investigate the association between
bullying and subjective health complaints. RESULTS: Victims of bullying were more
likely to report backache (Odds Ratio [OR] = 1.92, 95% CI: 1.01-3.67), dizziness
(OR = 2.83, 95% CI: 1.11-7.22) and fatigue (OR = 0.41, 95% CI: 0.19-0.86),
independently of the presence of psychiatric morbidity. In addition bullying
perpetrators were more likely to report backache (OR = 3.49, 95% CI: 1.49-8.18).
It is worth noting that sleep problems and abdominal pain were also associated
with being bullied and fatigue with bullying perpetration but these associations
were all attenuated after adjustment for psychiatric morbidity. CONCLUSIONS:
Strong associations between bullying in schools and subjective health complaints
among a sample of Greek students aged 16-18 years have been observed. The exact
nature of these associations should be investigated in future longitudinal
studies.
PMID- 25115325
TI - Is sacral neuromodulation here to stay? Clinical outcomes of a new treatment for
fecal incontinence.
AB - INTRODUCTION: Sacral neuromodulation (SNM) was approved by the FDA for the
treatment of fecal incontinence (FI) in 2011, and previous industry-sponsored
trials have shown excellent clinical outcomes. The purpose of this study is to
examine clinical outcomes of patients treated during our initial experience with
SNM. METHODS: A prospective database of patients treated with SNM for FI by one
of three colorectal surgeons at two separate institutions was maintained starting
in 2011. Patients showing >=50% improvement of weekly incontinent episodes during
test stimulation were offered permanent implantation of the SNM device. Disease
severity was tracked using the Wexner score. RESULTS: A total of 145 patients
received a full system implantation (of 152 who received test stimulation). The
median preoperative Wexner score of 14 decreased to 3, 3 months after
implantation and persisted to 12 months. At 12 months, 95.2% of patients achieved
>50% improvement in Wexner Score and 67.6% achieved >75% improvement. The most
common adverse event was infection (3.4%). Three patients (2.1%) required lead
revision. CONCLUSIONS: SNM is a safe and effective therapy for the treatment of
FI. Postoperative patient surveillance is important, as many patients require
programming changes, and some will require a lead revision over time.
PMID- 25115324
TI - Routine drainage of the operative bed following elective distal pancreatectomy
does not reduce the occurrence of complications.
AB - BACKGROUND: Routine drainage of the operative bed following elective
pancreatectomy remains controversial. Data specific to distal pancreatectomy (DP)
have not been examined in a multi-institutional collaborative. METHODS: Data from
the American College of Surgeons-National Surgical Quality Improvement Program
Pancreatectomy Demonstration Project were utilized. The impact of drain placement
on development of pancreatectomy-related and overall morbidity were analyzed.
Propensity scores for drain placement were calculated, and nearest neighbor
matching was used to create a matched cohort. Groups were compared using
bivariate and logistic regression analyses. RESULTS: Over 14 months, 761 patients
undergoing DP were accrued; 606 were drained. Propensity score matching was
possible in 116 patients. Drain and no drain groups were not different with
respect to multiple preoperative and operative variables. All pancreatic fistulas
(p < 0.01) and overall morbidity (p < 0.05) were more common in patients who
received a drain. The placement of a drain did not reduce the incidence of
clinically relevant pancreatic fistula nor the need for postoperative procedures.
CONCLUSIONS: Placement of drains following elective distal pancreatectomy was
associated with a higher overall morbidity and pancreatic fistulas. Drains did
not reduce intra-abdominal septic morbidity, clinically relevant pancreatic
fistulas, nor the need for postoperative therapeutic intervention.
PMID- 25115327
TI - Pushing with the pigtail: a novel approach to placing the MitraClip in a patient
with a severely restricted posterior mitral leaflet.
AB - The MitraClip is an US Food and Drug Administration-approved device for
inoperable patients with severe degenerative mitral regurgitation (MR) and is
under investigation for use in patients with severe functional MR. Simultaneously
grasping both leaflets of the mitral valve can be technically challenging,
however, in patients with a restricted posterior leaflet. We present one such
case in which a pigtail catheter, placed retrograde into the left ventricle, was
able to push the ventricular surface of the posterior leaflet into closer
approximation with the anterior leaflet, and facilitate successful clip
placement. We provide this report in hopes that it will provide a useful strategy
for interventionalists faced with this challenging situation.
PMID- 25115326
TI - Superglue in the Urethra: Surgical Treatment.
AB - We describe a case of superglue application into the male urethra with successful
surgical treatment of the glue particles by external urethrotomy.
PMID- 25115328
TI - 'A Speculative Idea': The Parallel Trajectories of Financial Speculation,
Obstetrical Science, and Fiscal Management of Female Bodies in Henry James's
Washington Square.
AB - This essay teases out the intimate connections between the scientific and fiscal
realms in the context of American germ theory and obstetrics. By uncovering the
economic and medical contexts of Henry James's Washington Square-set during the
infancy of germ theory and the heyday of American obstetrics-this essay exposes a
previously unexplored subtextual history of contagion in the text. Although this
scientific history seems relegated to the novel's margins, understanding the
changing scientific cosmologies and professional organizations in the context of
the novel's setting and composition reveals that these tiny infectious particles
and their vectors fundamentally shape the plot of the novel.
PMID- 25115329
TI - Phenyl amide linker improves the pharmacokinetics and pharmacodynamics of N
terminally mono-PEGylated human growth hormone.
AB - Human growth hormone (hGH) suffers from a short plasma half-life of ~15 min,
necessitating frequent injections to maintain its physiological effect.
PEGylation, conjugation of polyethylene glycol (PEG), is an effective strategy to
prolong the plasma half-life of hGH. However, PEGylation can significantly
decrease the bioactivity of hGH. Thus, a new PEGylation approach is desired to
improve the pharmacokinetics (PK) and pharmacodynamics (PD) of the PEGylated hGH.
In the present study, two N-terminally mono-PEGylated hGHs were prepared using
aldehyde chemistry. Phenyl amide and ethyl moieties were used as the linkers
between PEG and hGH, respectively. The hydrodynamic volume, proteolytic
sensitivity, and immunogenicity of the PEGylated hGH with phenyl amide linker
(hGH-phenyl-PEG) were lower than those of the one with propyl linker (hGH-prop
PEG). In addition, hGH-phenyl-PEG showed a higher in vitro bioactivity and better
PK and PD than hGH-prop-PEG. The better PK of hGH-phenyl-PEG was mainly due to
its lower proteolytic sensitivity and low immunogenicity. The better PD of hGH
phenyl-PEG was mainly due to its higher in vitro bioactivity. Thus, the phenyl
amide linker can improve the overall pharmacological profiles of the PEGylated
hGH. Our study is expected to advance the development of long-acting protein
biotherapeutics with high therapeutic efficacy.
PMID- 25115331
TI - KiMoSys: a web-based repository of experimental data for KInetic MOdels of
biological SYStems.
AB - BACKGROUND: The kinetic modeling of biological systems is mainly composed of
three steps that proceed iteratively: model building, simulation and analysis. In
the first step, it is usually required to set initial metabolite concentrations,
and to assign kinetic rate laws, along with estimating parameter values using
kinetic data through optimization when these are not known. Although the rapid
development of high-throughput methods has generated much omics data,
experimentalists present only a summary of obtained results for publication, the
experimental data files are not usually submitted to any public repository, or
simply not available at all. In order to automatize as much as possible the steps
of building kinetic models, there is a growing requirement in the systems biology
community for easily exchanging data in combination with models, which represents
the main motivation of KiMoSys development. DESCRIPTION: KiMoSys is a user
friendly platform that includes a public data repository of published
experimental data, containing concentration data of metabolites and enzymes and
flux data. It was designed to ensure data management, storage and sharing for a
wider systems biology community. This community repository offers a web-based
interface and upload facility to turn available data into publicly accessible,
centralized and structured-format data files. Moreover, it compiles and
integrates available kinetic models associated with the data.KiMoSys also
integrates some tools to facilitate the kinetic model construction process of
large-scale metabolic networks, especially when the systems biologists perform
computational research. CONCLUSIONS: KiMoSys is a web-based system that
integrates a public data and associated model(s) repository with computational
tools, providing the systems biology community with a novel application
facilitating data storage and sharing, thus supporting construction of ODE-based
kinetic models and collaborative research projects.The web application
implemented using Ruby on Rails framework is freely available for web access at
http://kimosys.org, along with its full documentation.
PMID- 25115333
TI - Endothelial cationic amino acid transporter-1 overexpression blunts the effects
of oxidative stress on pressor responses to behavioural stress in mice.
AB - Observational studies indicate that psychological stress may contribute to the
pathogenesis of hypertension and this may be further accentuated by factors such
as endothelial dysfunction. On this basis, we aimed to determine whether
oxidative stress enhances pressor responses to stressful stimuli and whether
augmenting endothelial function by increasing the transport of L-arginine can
counter the effects of oxidative stress. Telemetry probes were used to measure
mean arterial pressure (MAP) in wild-type (WT; n = 6) and endothelial cationic
amino acid transporter-1 (CAT-1)-overexpressing (CAT+) mice (n = 6) before and
during an aversive (restraint) and non-aversive (almond feeding) stressor. The
superoxide dismutase inhibitor diethyldithiocarbamic acid (DETCA; 30 mg/kg per
day; 14 days) was then administered via a minipump to induce oxidative stress.
Stress responses to feeding and restraint were repeated during Days 11-12 of
DETCA infusion. In WT mice, pressor responses to restraint and feeding were
augmented during infusion of DETCA (35 +/- 1 and 28 +/- 1 mmHg, respectively)
compared with respective pretreatment responses (28 +/- 2 and 24 +/- 1 mmHg,
respectively; P <= 0.01). In CAT+ mice, pressor responses to feeding were blunted
during DETCA (20 +/- 1 mmHg) compared with the control response (23 +/- 1 mmHg; P
= 0.03). In these mice, pressor responses to restraint were similar before (28 +/
1 mmHg) and during (26 +/- 1 mmHg) DETCA infusion (P = 0.26). We conclude that
endothelial CAT-1 overexpression can counter the ability of oxidative stress to
augment pressor responses to behavioural stress.
PMID- 25115334
TI - Effects of framework design and layering material on fracture strength of implant
supported zirconia-based molar crowns.
AB - OBJECTIVES: To evaluate the effects of framework design and layering material on
the fracture strength of implant-supported zirconia-based molar crowns. MATERIAL
AND METHODS: Sixty-six titanium abutments (GingiHue Post) were tightened onto
dental implants (Implant Lab Analog). These abutment-implant complexes were
randomly divided into three groups (n = 22) according to the design of the
zirconia framework (Katana), namely, uniform-thickness (UNI), anatomic (ANA), and
supported anatomic (SUP) designs. The specimens in each design group were further
divided into two subgroups (n = 11): zirconia-based all-ceramic restorations (ZAC
group) and zirconia-based restorations with an indirect composite material
(Estenia C&B) layered onto the zirconia framework (ZIC group). All crowns were
cemented on implant abutments, after which the specimens were tested for fracture
resistance. The data were analyzed with the Kruskal-Wallis test and the Mann
Whitney U-test with the Bonferroni correction (alpha = 0.05). RESULTS: The
following mean fracture strength values (kN) were obtained in UNI design, ANA
design, and SUP design, respectively: Group ZAC, 3.78, 6.01, 6.50 and Group ZIC,
3.15, 5.65, 5.83. In both the ZAC and ZIC groups, fracture strength was
significantly lower for the UNI design than the other two framework designs (P =
0.001). Fracture strength did not significantly differ (P > 0.420) between
identical framework designs in the ZAC and ZIC groups. CONCLUSIONS: A framework
design with standardized layer thickness and adequate support of veneer by
zirconia frameworks, as in the ANA and SUP designs, increases fracture resistance
in implant-supported zirconia-based restorations under conditions of chewing
attrition. Indirect composite material and porcelain perform similarly as
layering materials on zirconia frameworks.
PMID- 25115335
TI - Evaluation of IAUGC indices and two DCE-MRI pharmacokinetic parameters assessed
by two different theoretical algorithms in patients with brain tumors.
AB - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) quantifies blood
brain barrier (BBB) microvascular permeability in brain tumors where it is
structurally and functionally abnormal. Twenty-five patients with glioblastomas
(105 regions of interest) were compared using DCE-MRI metrics obtained with Tofts
Kety (TK) and extended TK (ETK) models using different arterial input function
assessments and different initial area under the gadolinium curve (IAUGC)
indices. Strong correlations between ve and IAUGC90 were found (EKT model: R=0.75
and R=0.69), while correlations of K(trans) with both IAUGC80/90 indices were
weak. Differences in the permeability parameters, calculated by these two models,
were found. While the IAUGC method can be implemented more easily than
pharmacokinetic models, at this time, the IAUGC approach alone does not
substitute pharmacokinetic models in BBB permeability characterization.
PMID- 25115336
TI - A new filaggrin gene mutation in a Korean patient with ichthyosis vulgaris.
PMID- 25115332
TI - Cannabinoid receptor 2 as a potential therapeutic target in rheumatoid arthritis.
AB - BACKGROUND: Some of cannabinoids, which are chemical compounds contained in
marijuana, are immunosuppressive. One of the receptors, CB receptor 1 (CB1), is
expressed predominantly by the cells in the central nervous system, whereas CB
receptor 2 (CB(2)) is expressed primarily by immune cells. Theoretically,
selective CB(2) agonists should be devoid of psychoactive effects. In this study,
we investigated therapeutic effects of a selective CB(2) agonist on arthritis.
METHODS: The expression of CB(2) was analyzed with immunohistochemistry and
Western blotting. Interleukin (IL)-6, matrix metalloproteinase-3 (MMP-3), and
chemokine (C-C motif) ligand 2 (CCL2) were quantified with enzyme-linked
immunosorbent assays (ELISA). Osteoclastogenesis was assessed with tartrate
resistant acid phosphatase staining and the resorption of coated-calcium
phosphate. Effect of JWH133, a selective CB(2) agonist, on murine collagen type
II (CII)-induced arthritis (CIA) was evaluated with arthritis score, and
histological and radiographic changes. IFN-gamma and IL-17 production by CII
stimulated splenocytes and serum anti-CII Ab were analyzed by ELISA. RESULTS:
Immunohistochemistry showed that CB(2) was expressed more in the synovial tissues
from the rheumatoid joints than in those from the osteoarthritis joints. CB(2)
expression on RA FLS was confirmed with Western blot analysis. JWH133 inhibited
IL-6, MMP-3, and CCL2 production from tumor necrosis factor-alpha-stimulated
fibroblast-like synoviocytes (FLS) derived from the rheumatoid joints, and
osteoclastogenesis of peripheral blood monocytes. Administration of JWH133 to CIA
mice reduced the arthritis score, inflammatory cell infiltration, bone
destruction, and anti-CII IgG1 production. CONCLUSION: The present study suggests
that a selective CB(2) agonist could be a new therapy for RA that inhibits
production of inflammatory mediators from FLS, and osteoclastogenesis.
PMID- 25115337
TI - Three-dimensional bicomponent supramolecular nanoporous self-assembly on a hybrid
all-carbon atomically flat and transparent platform.
AB - Molecular self-assembly is a versatile nanofabrication technique with atomic
precision en route to molecule-based electronic components and devices. Here, we
demonstrate a three-dimensional, bicomponent supramolecular network architecture
on an all-carbon sp(2)-sp(3) transparent platform. The substrate consists of
hydrogenated diamond decorated with a monolayer graphene sheet. The pertaining
bilayer assembly of a melamine-naphthalenetetracarboxylic diimide supramolecular
network exhibiting a nanoporous honeycomb structure is explored via scanning
tunneling microscopy initially at the solution-highly oriented pyrolytic graphite
interface. On both graphene-terminated copper and an atomically flat
graphene/diamond hybrid substrate, an assembly protocol is demonstrated yielding
similar supramolecular networks with long-range order. Our results suggest that
hybrid platforms, (supramolecular) chemistry and thermodynamic growth protocols
can be merged for in situ molecular device fabrication.
PMID- 25115338
TI - The forgotten members of the glucagon family.
AB - From proglucagon, at least six final biologically active peptides are produced by
tissue-specific post-translational processing. While glucagon and GLP-1 are the
subject of permanent studies, the four others are usually left in the shadow, in
spite of their large biological interest. The present review is devoted to
oxyntomodulin and miniglucagon, not forgetting glicentin, although much less is
known about it. Oxyntomodulin (OXM) and glicentin are regulators of gastric acid
and hydromineral intestinal secretions. OXM is also deeply involved in the
control of food intake and energy expenditure, properties that make this peptide
a credible treatment of obesity if the question of administration is solved, as
for any peptide. Miniglucagon, the C-terminal undecapeptide of glucagon which
results from a secondary processing of original nature, displays properties
antagonistic to that of the mother-hormone glucagon: (a) it inhibits glucose-,
glucagon- and GLP-1-stimulated insulin release at sub-picomolar concentrations,
(b) it reduces the in vivo insulin response to glucose with no change in
glycemia, (c) it displays insulin-like properties at the cellular level using
only a part of the pathway used by insulin, making it a good basis for developing
a pharmacological workaround of insulin resistance.
PMID- 25115339
TI - Study to assess whether waist circumference and changes in serum glucose and
lipid profile are independent variables for the CETP gene.
AB - AIMS: To observe the relationship among genes, obesity and the changes in serum
glucose and lipid profile to assess whether obesity-related disease results from
genes and/or obesity. METHODS: Correlations among serum glucose, lipids, waist
circumference (WC), and Taq1B, I405V, and D442G polymorphisms of the cholesteryl
ester transfer protein (CETP) gene were assessed. Logistic regression analysis
was used to screen independent variables among obesity-related anthropometric
indexes and serum biochemical indicators for genes. RESULTS: The waist
circumference density index (WCDI) may be attributed to changes in serum
biochemical indicators and among WCDI, BMI and serum biochemical indicators,
however, only WCDI was an independent variable for the G allele. Differences were
observed in anthropometric indexes and serum biochemical indicators between
subjects with the G allele and those without (p<0.05). CONCLUSION: Abdominal
obesity and changes in serum glucose and lipid profile are affected by a group of
genes, including CETP. Correlation of the CETP gene with waist circumference may
be independent compared with serum glucose and lipid profile.
PMID- 25115340
TI - Prevalence and correlates of alcohol abuse and dependence in Lebanon: results
from the Lebanese Epidemiologic Survey on Alcohol (LESA).
AB - The current article aimed to determine the 12-month prevalence and correlates of
DSM-IV alcohol abuse and dependence in a nationally representative sample of
Lebanese adults. One thousand participants collaborated in face-to-face
interviews in 2011. Prevalence of 12-month alcohol dependence was 5%, with a
higher risk for those who were men, unmarried, the youngest adults (aged between
18 and 34 years old), students, participants with a liberal occupation,
participants with a low income, participants with a positive family history of
alcohol misuse, and smokers. Prevalence of 12-month alcohol abuse was 6.2%, with
a higher risk for those who were men, students, employees, and Druze and
Christians compared to Muslims. Current alcohol abuse and dependence were found
to be very highly prevalent in Lebanon.
PMID- 25115341
TI - Cross-reacting material 197, a heparin-binding EGF-like growth factor inhibitor,
reverses the chemoresistance in human cisplatin-resistant ovarian cancer.
AB - Cross-reacting material 197 (CRM197), a specific HB-EGF inhibitor, has been
proven to be a promising antitumor agent for ovarian cancer therapy. Our previous
studies have shown that CRM197 has potent antitumor activity in human cisplatin
resistant ovarian cancer. However, the relationship between CRM197 and the
resistance to cisplatin remains unclear. Here, we report that CRM197
significantly reverses the resistance to cisplatin in cisplatin-resistant ovarian
carcinoma cell line (A2780/CDDP). We established xenograft nude mice models with
A2780 and A2780/CDDP cells. Notably, we observed that CRM197 suppresses the
expression of HB-EGF and epidermal growth factor receptor in A2780/CDDP cells and
xenografts harboring the overexpression of HB-EGF and epidermal growth factor
receptor. Experiments conducted in vitro and in vivo suggest that CRM197 markedly
downregulates the expression of excision repair cross-complementing group 1 (P =
0.002) and DNA repair capacity in A2780/CDDP tumor (P < 0.001) by inactivation of
extracellular signal-regulated kinase signaling, providing novel possible
mechanisms for the ability of CRM197 to restore drug sensitivity. These results
suggest that CRM197 as an HB-EGF inhibitor might be a cisplatin-chemosensitizing
agent for the treatment of ovarian carcinoma with resistance to cisplatin.
PMID- 25115342
TI - Nab-paclitaxel for the management of triple-negative metastatic breast cancer: a
case study.
AB - The optimal sequence of systemic chemotherapy in metastatic breast cancer (MBC)
is unknown. We report the case of a woman who was successfully treated with
nanoparticle albumin-bound (nab)-paclitaxel for triple negative MBC in our
institution. In November 2008, a 48-year-old woman underwent surgical treatment
for a triple negative invasive ductal breast cancer and subsequently received
adjuvant chemotherapy with fluorouracil/epirubicin/cyclophosphamide and
radiotherapy. Sixteen months after surgery, she presented with a left chest wall
metastatasis. The patient received combination therapy with conventional
paclitaxel (90 mg/m2 weekly for 3 out of 4 weeks [QW 3/4]) and bevacizumab (10
mg/kg every 2 weeks [Q2W]) as first-line treatment for MBC (six cycles; March to
September 2010) and achieved a partial response at the metastatic site.
Bevacizumab monotherapy was continued until disease progression (April 2011) with
the development of a single infraclavicular lymph node metastasis and an increase
in the dimensions of the left chest wall lesion. From May to December 2011, the
patient received nab-paclitaxel 260 mg/m2 every 3 weeks (Q3W) as second-line
treatment (11 cycles). After three cycles, the left chest wall lesion and the
infraclavicular lymph node metastasis were undetectable and the patient was
considered to have achieved a complete response. Treatment was well tolerated
with no significant toxicity or need for dose reduction. Given our case, here we
review the clinical evidence and discuss the potential role of nab-paclitaxel for
the treatment of triple negative MBC, a subgroup typically characterized as
having aggressive disease and limited treatment options.
PMID- 25115343
TI - Methicillin-resistant Staphylococcus aureus infection: an independent risk factor
for mortality in patients with poststernotomy mediastinitis.
AB - OBJECTIVE: The mortality rate of patients with poststernotomy mediastinitis
remains very high. The aim of this study was to identify the risk factors
associated with mortality in these patients. SUBJECTS AND METHODS: Surveillance
of sternal surgical-site infections including mediastinitis was carried out for
adult patients undergoing a sternotomy between 2004 and 2012. Criteria from the
US Centers for Disease Control and Prevention were used to make the diagnosis.
All data on patients with a diagnosis of mediastinitis who were included in the
study and on mortality risk factors were obtained from the hospital database and
then analyzed using SPPS 16.0 for Windows. RESULTS: Of the 19,767 patients
undergoing open heart surgery, 117 (0.39%) had poststernotomy mediastinitis; 32%
of these 117 died. The independent risk factors for mortality were methicillin
resistant Staphylococcus aureus (MRSA) [odds ratio (OR) 12.11 and 95% confidence
interval (CI) 3.15-46.47], intensive-care unit stays >48 h after the first
operation (OR 11.21 and 95% CI 3.24-38.84) and surgery that included valve
replacement (OR 6.2 and 95% CI 1.44-27.13). The mortality rate decreased
significantly, dropping from 38% (34/89) between 2004 and 2008 to 14% (4/28)
between 2009 and 2012 (p = 0.018). CONCLUSION: In this study, elimination of MRSA
from the hospital setting decreased the rate of mortality in patients with
poststernotomy mediastinitis.
PMID- 25115344
TI - Effects of dietary threonine and tryptophan supplementation on growing pigs
induced by porcine respiratory and reproductive syndrome vaccination.
AB - A total of 32 growing pigs were used in a 2 * 2 factorial arrangement of
treatments with two different diets (conventional [CON] diet vs. threonine [Thr]-
and tryptophan [Trp]-rich [TTR] diet) and two immunological challenge regimens
(porcine respiratory and reproductive syndrome [PRRS] vaccine vs. phosphate
buffer solution [PBS]) to study the hypothesis that dietary supplementation with
Trp and Thr would benefit for growing pigs vaccinated with PRRS vaccine. After
feeding the experimental diets for 21 d, the pigs were intramuscularly vaccinated
with PRRS or PBS. Performance data were recorded over a period of 10 weeks and
are presented for the pre-challenge period (3 weeks) and the challenge period (7
weeks, where on day 1, pigs were immunologically challenged). During the pre
challenge period, the growth performance was not different between dietary
treatments. PRRS vaccination resulted in increased rectal temperature and
decreased feed intake and growth rate (p < 0.05). In PRRS-vaccinated pigs, diet
TTR enhanced the feed intake, especially during the first 2 weeks after the PRRS
vaccination compared with diet CON (p < 0.05). PRRS vaccination also resulted in
increased plasma concentration of urea nitrogen, essential and non-essential
amino acids (p < 0.05) and porcine reproductive and respiratory syndrome virus
specific antibodies (p < 0.05), but decreased concentration of immunoproteins
including alpha-1-acylglycoprotein and immunoglobulin G (p < 0.05). The
alleviation of the PRRS vaccination induced decrease in feed intake and growth
rate by Thr and Trp supplementation, indicating that the PRRS-vaccinated pigs had
a higher Thr and Trp requirement than non-vaccinated pigs.
PMID- 25115345
TI - Management of obesity in children differs from that of adults.
AB - Obesity in childhood is a very common disorder with an increasing prevalence. It
is one of the most serious public health challenges. The objectives of the
present paper are to increase the awareness of the problem of obesity in
childhood, its serious complications and the need for prevention. Overweight and
obese children are likely to remain obese into adulthood and more likely to
develop serious complications including health problems such as diabetes and CVD,
as well as psychological and social challenges. Overweight and obesity are
largely preventable. In adults it is difficult to reduce excessive weight gain
once it has become established, thus children should be considered the priority
population for intervention strategies and prevention. Nutrition, exercise,
weight gain in infancy, genetic and environmental factors, all contribute to the
aetiology. Prevention and treatment of obesity in childhood requires education
and empowerment of families relating to diet and exercise, along with the
regulation and control of food marketing and clear nutritional labelling. The
eating and physical activity behaviour of a child is strongly influenced by
environmental and social factors. Therefore treatment will have only limited
success in an environment where adequate physical activity is inhibited and the
consumption of high-energy food is stimulated. Government investment in a health
promotion programme addressing the issue of obesity in the population as a whole,
with particular emphasis on the prevention and management of obesity in childhood
is vital. The family doctor and multidisciplinary team play an important role.
Regular visits to the family doctor, including growth assessment, will help
motivate the family to restrict energy intake and to increase exercise. Therefore
the prevention of childhood obesity needs high priority.
PMID- 25115346
TI - Deficits in visuo-spatial but not in topographical memory during pregnancy and
the postpartum state in an expert military pilot: a case report.
AB - BACKGROUND: It is well known that cognitive and emotional changes occur during
pregnancy, but little is known about their magnitude or their time of occurrence
and recovery. During pregnancy memory is one of the most impaired cognitive
functions. Although long-term aspects of memory have been investigated, other
aspects of memory have not yet been explored (i.e., navigational memory and
reaching memory). CASE PRESENTATION: Here we describe the changes in reaching and
walking memory that occurred during pregnancy and one year after delivery in an
Italian female military pilot (Case 1) with high spatial ability. In memory tests
she showed a classical dissociation between performance in reaching and walking
distance, which indicated a failure of working memory, learning, and storage in
reaching space. This suggests that her expertise served as a protective factor
mitigating her low walking memory performance, and saving the topographical
component.We compared her performance with that of two non-pregnant control
groups (i.e., women pilots and non-pilots) and found that Case 1's reaching
memory performance was significantly worse than that of the control groups. Even
one year postpartum, Case 1's performance was not yet the same as that of the
other pilots. CONCLUSIONS: These findings contribute to our knowledge of the
specific, as yet unexplored, aspects of memory deficits in women pilots during
pregnancy and postpartum and suggest the need for better neuropsychological
assessment before these women return to work in operational environments.
PMID- 25115347
TI - The Effect of Ankle Taping to Restrict Plantar Flexion on Ball and Foot Velocity
During an Instep Kick in Soccer.
AB - CONTEXT: Posterior ankle impingement syndrome is a common disorder in soccer
players and ballet dancers. In soccer players, it is caused by the repetitive
stress of ankle plantar flexion due to instep kicking. Protective ankle
dorsiflexion taping is recommended with the belief that it prevents posterior
ankle impingement. However, the relationship between ankle taping and ball
kicking performance remains unclear. OBJECTIVE: To demonstrate the relationship
between the restrictions of ankle taping and performance of an instep kick in
soccer. DESIGN: Laboratory-based repeated-measures. SETTING: University
laboratory. PARTICIPANTS: 11 male university soccer players. INTERVENTION: The
subjects' ankle plantar flexion was limited by taping. Four angles of planter
flexion (0 degrees , 15 degrees , 30 degrees , and without taping) were formed by
gradation limitation. The subjects performed maximal instep kicks at each angle.
MAIN OUTCOME MEASURES: The movements of the kicking legs and the ball were
captured using 3 high-speed cameras at 200 Hz. The direct linear-transformation
method was used to obtain 3-dimensional coordinates using a digitizing system.
Passive ankle plantar-flexion angle, maximal plantar-flexion angle at ball
impact, ball velocity, and foot velocity were measured. The data were compared
among 4 conditions using repeated-measures ANOVA, and the correlations between
ball velocity and foot velocity and between ball velocity and toe velocity were
calculated. RESULTS: Ankle dorsiflexion taping could gradually limit both passive
plantar flexion and plantar flexion at the impact. Furthermore, limitation of 0
degrees and 15 degrees reduced the ball velocity generated by instep kicks.
CONCLUSION: Plantar-flexion-limiting taping at 30 degrees has a potential to
prevent posterior ankle impingement without decreasing the ball velocity
generated by soccer instep kicks.
PMID- 25115349
TI - Quantification of gastrointestinal liquid volumes and distribution following a
240 mL dose of water in the fasted state.
AB - The rate and extent of drug dissolution and absorption from solid oral dosage
forms is highly dependent upon the volumes and distribution of gastric and small
intestinal water. However, little is known about the time courses and
distribution of water volumes in vivo in an undisturbed gut. Previous imaging
studies offered a snapshot of water distribution in fasted humans and showed that
water in the small intestine is distributed in small pockets. This study aimed to
quantify the volume and number of water pockets in the upper gut of fasted
healthy humans following ingestion of a glass of water (240 mL, as recommended
for bioavailability/bioequivalence (BA/BE) studies), using recently validated
noninvasive magnetic resonance imaging (MRI) methods. Twelve healthy volunteers
underwent upper and lower abdominal MRI scans before drinking 240 mL (8 fluid
ounces) of water. After ingesting the water, they were scanned at intervals for 2
h. The drink volume, inclusion criteria, and fasting conditions matched the
international standards for BA/BE testing in healthy volunteers. The images were
processed for gastric and intestinal total water volumes and for the number and
volume of separate intestinal water pockets larger than 0.5 mL. The fasted
stomach contained 35 +/- 7 mL (mean +/- SEM) of resting water. Upon drinking, the
gastric fluid rose to 242 +/- 9 mL. The gastric water volume declined rapidly
after that with a half emptying time (T50%) of 13 +/- 1 min. The mean gastric
volume returned back to baseline 45 min after the drink. The fasted small bowel
contained a total volume of 43 +/- 14 mL of resting water. Twelve minutes after
ingestion of water, small bowel water content rose to a maximum value of 94 +/-
24 mL contained within 15 +/- 2 pockets of 6 +/- 2 mL each. At 45 min, when the
glass of water had emptied completely from the stomach, total intestinal water
volume was 77 +/- 15 mL distributed into 16 +/- 3 pockets of 5 +/- 1 mL each. MRI
provided unprecedented insights into the time course, number, volume, and
location of water pockets in the stomach and small intestine under conditions
that represent standard BA/BE studies using validated techniques. These data add
to our current understanding of gastrointestinal physiology and will help improve
physiological relevance of in vitro testing methods and in silico transport
analyses for prediction of bioperformance of oral solid dosage forms,
particularly for low solubility Biopharmaceutics Classification System (BCS)
Class 2 and Class 4 compounds.
PMID- 25115350
TI - Commentary on highlighted late breaking trials in interventional cardiology at
ESC, VIVA, TCT, and AHA 2013.
AB - With the plethora of clinical trials, it is difficult for busy interventional
cardiologists to stay up to date. Therefore, the SCAI publications committee
concisely summarizes and provides editorial commentary on the most important
trials from recent, large international meetings. The intent is to provide this
summary every six months to allow quick assimilation of trial results into
interventional practice. (c) 2014 Wiley Periodicals, Inc.
PMID- 25115352
TI - Effects of washing of the face with a mild facial cleanser formulated with sodium
laureth carboxylate and alkyl carboxylates on acne in Japanese adult males.
AB - BACKGROUND/PURPOSE: Washing the face with a mild cleanser is generally
recommended for acne care. Occasionally, the general public has the misconception
that acne is exacerbated by cleansers and furthermore it has concerns about
inducing skin irritation and xerosis by intensive washing. Recently, we developed
a new cleanser based on sodium laureth carboxylate and alkyl carboxylates
(AEC/soap) that cleans sebum well without penetrating the stratum corneum.
METHODS: We designed a controlled clinical trial conducted on adult Japanese
males with moderate or less acne. Twenty subjects washed their faces with
AEC/soap base cleanser twice a day for 4 weeks. Assessment of the efficacy was
conducted prior to the start of the study, and at the end of weeks 2 and 4.
RESULTS: Significant improvement of the acne was observed within 2 weeks, and
acne lesions were not detectable in 25% of the subjects at week 4. Sebum
secretion levels on the skin significantly increased on the forehead, but
significantly decreased on the cheek which correlated with the improvement. No
complaints of dryness or irritation occurred during the study. CONCLUSION:
Washing the face twice a day with facial cleanser based on AEC/soap is an
effective care for moderate or less grade facial acne.
PMID- 25115351
TI - Proteomics-based metabolic modeling and characterization of the cellulolytic
bacterium Thermobifida fusca.
AB - BACKGROUND: Thermobifida fusca is a cellulolytic bacterium with potential to be
used as a platform organism for sustainable industrial production of biofuels,
pharmaceutical ingredients and other bioprocesses due to its capability of
potential to convert plant biomass to value-added chemicals. To best develop T.
fusca as a bioprocess organism, it is important to understand its native cellular
processes. In the current study, we characterize the metabolic network of T.
fusca through reconstruction of a genome-scale metabolic model and proteomics
data. The overall goal of this study was to use multiple metabolic models
generated by different methods and comparison to experimental data to gain a high
confidence understanding of the T. fusca metabolic network. RESULTS: We report
the generation of three versions of a metabolic model of Thermobifida fusca sp.
XY developed using three different approaches (automated, semi-automated, and
proteomics-derived). The model closest to in vivo growth was the proteomics
derived model that consists of 975 reactions involving 1382 metabolites and
account for 316 EC numbers (296 genes). The model was optimized for biomass
production with the optimal flux of 0.48 doublings per hour when grown on
cellobiose with a substrate uptake rate of 0.25 mmole/h. In vivo activity of the
DXP pathway for terpenoid biosynthesis was also confirmed using real-time PCR.
CONCLUSIONS: iTfu296 provides a platform to understand and explore the metabolic
capabilities of the actinomycete T. fusca for the potential use in bioprocess
industries for the production of biofuel and pharmaceutical ingredients. By
comparing different model reconstruction methods, the use of high-throughput
proteomics data as a starting point proved to be the most accurate to in vivo
growth.
PMID- 25115353
TI - KCNJ11 E23K variant is associated with the therapeutic effect of sulphonylureas
in Chinese type 2 diabetic patients.
AB - The aim of the present study was to investigate the effect of the E23K variant of
the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene
on gliclazide modified release (MR) treatment in newly diagnosed patients with
type 2 diabetes mellitus (T2DM). A total of 108 diabetic patients with no history
of antidiabetic medication was treated with gliclazide MR for 16 weeks and
underwent follow up at Weeks 2, 4, 8, 12 and 16. All patients were genotyped for
KCNJ11 E23K (rs5219). At baseline, patients with the KK genotype had higher blood
glucose and lower serum insulin levels after oral glucose administration than
patients with the EE and EK genotypes (P < 0.05 for all). During treatment,
individuals with the KK genotype had lower fasting glucose levels and were more
likely to attain the target fasting glucose level (Plog rank = 0.028) than E
allele carriers. Patients with the KK genotype had larger augmentations in
changes (Delta) in acute insulin response (P = 0.049) and Delta body mass index
(P = 0.003). Moreover, patients with the EK genotype had a lower variance in
changes in fasting insulin levels (P = 0.049) and homeostasis model assessment of
beta-cell function (P = 0.021) than those with the KK genotype. The findings of
the present study suggest that the KCNJ11 E23K variant is associated with a
greater effect of sulphonylurea treatment in newly diagnosed Chinese patients
with T2DM.
PMID- 25115355
TI - Locking versus non-locking plate fixation in the management of mandibular
fractures: a meta-analysis.
AB - The aim of the present study was to test whether there is a significant
difference in the clinical outcomes between locking and non-locking plate
fixation in the management of mandibular fractures. An electronic search without
time or language restrictions was undertaken in December 2013. Eligible studies
were clinical human studies, either randomized or not. The search strategy
identified 10 publications. The I(2) statistic was used to express the percentage
of the total variation across studies due to heterogeneity. The inverse variance
method was used for the random-effects model in the case of heterogeneity being
detected, or the fixed-effects model in the case of heterogeneity not being
detected. The estimates of an intervention were expressed as the risk ratio (RR)
with 95% confidence interval. Eight studies were judged to be at high risk of
bias, whereas two studies were considered at moderate risk of bias. There was no
statistically significant effect on the outcome of postoperative infection
(P=0.17), malocclusion (P=0.15), hardware failure (P=0.77), hardware removal
(P=0.95), wound dehiscence (P=0.98), or paraesthesia (P=0.20) in favour of
locking plate fixation. The test for overall effect showed that the difference
between the procedures did not significantly affect the incidence of
postoperative complications (P=0.21), with RR 0.79 (95% CI 0.54-1.14).
PMID- 25115354
TI - Evaluation of the measurement properties of the Manchester foot pain and
disability index.
AB - BACKGROUND: The Manchester Foot Pain and Disability Index (MFPDI, 19 items) was
developed to measure functional limitations, pain and appearance for patients
with foot pain and is frequently used in both observational studies and
randomised controlled trials. A Dutch version of the MFPDI was developed. The
aims of this study were to evaluate all the measurement properties for the Dutch
version of the MFPDI and to evaluate comparability to the original version.
METHOD: The MFPDI was translated into Dutch using a forward/backward translation
process. The dimensionality was evaluated using exploratory and confirmatory
factor analysis. Measurement properties were evaluated per subscale according to
the COSMIN taxonomy consisting of: reliability (internal consistency, test-retest
reliability and measurement error), validity (structural validity, content
validity and cross-cultural validity comparing the Dutch version to the English
version) responsiveness and interpretation. RESULTS: The questionnaire consists
of three scales, measuring foot function, foot pain and perception. The
reliability of the foot function scale is acceptable (Cronbach's alpha > 0.7, ICC
= 0.7, SEM = 2.2 on 0-18 scale). The construct validity of the function and pain
scale was confirmed and only the pain scale contains one item with differential
item functioning (DIF). The responsiveness of the function and pain scale is
moderate when compared to anchor questions. CONCLUSION: Results using the Dutch
MFPDI version can be compared to results using the original version. The foot
function sub-scale (items 1-9) is a reliable and valid sub-scale. This study
indicates that the use of the MFPDI as a longitudinal instrument might be
problematic for measuring change in musculoskeletal foot pain due to moderate
responsiveness.
PMID- 25115356
TI - Eosinophilic leukocytoclastic vasculitis - a spectrum ranging from Wells'
syndrome to Churg-Strauss syndrome?
AB - BACKGROUND: Wells' syndrome is defined as an inflammatory disorder with the
histopathological presence of eosinophilic infiltrates and flame figures in the
absence of vasculitis. Eosinophilic leukocytoclastic vasculitis shows
eosinophilic infiltrates in combination with vasculitic changes. And Churg
Strauss Syndrome comprises all three characteristics - eosinophilic infiltrates,
vasculitis and flame figures. OBJECTIVE: To determine whether these three
diseases are distinct entities or different manifestations of a similar
clinicopathologic process. METHOD: Histopathological samples and clinical courses
of 17 patients with eosinophilic infiltrates, flame figures and clinical features
of Wells' syndrome were re-evaluated. Histopathologically, we focused on the
presence or absence of vasculitic features. Clinically, we included only patients
who were diagnosed with Wells' syndrome at least once in the course of their
disease. RESULTS: 4 patients were finally diagnosed with Wells' syndrome, 5 with
eosinophilic leukocytoclastic vasculitis and 6 with Churg Strauss syndrome.
Further, we had one case of an overlap between Wells' syndrome and eosinophilic
vasculitis and one case of Wegener granulomatosis. Vasculitic features were found
in the samples of all patients. CONCLUSIONS: Histologically, we find vasculitic
features in typical presentations of Wells' syndrome. Clinically, we find typical
features of Wells' syndrome in patients finally diagnosed with eosinophilic
leukocytoclastic vasculitis or Churg Strauss syndrome. Furthermore, we have
observed and formerly reported 3 patients with progression from Wells' syndrome
to Churg Strauss syndrome. Thus, we assume that eosinophilic leukocytoclastic
vasculitis might form a bridge between Wells' syndrome and Churg Strauss
syndrome.
PMID- 25115357
TI - Room-temperature direct alkynylation of arenes with copper acetylides.
AB - C-H bond in azoles and polyhalogenated arenes can be smoothly activated by copper
acetylides to give the corresponding alkynylated (hetero)arenes by simple
reaction at room temperature in the presence of phenanthroline and lithium tert
butoxide under an oxygen atmosphere. These stable, unreactive, and readily
available polymers act as especially efficient and practical reagents for the
introduction of an alkyne group to a wide number of arenes under remarkably mild
conditions.
PMID- 25115358
TI - Laparoscopic ureteral reimplantation underneath broad ligament tunnel for female
vesicoureteral stenosis: a technical innovation.
AB - INTRODUCTION: In order to anatomically reconstruct ureteral stenosis, we present
a novel technique for laparoscopic ureteral reimplantation. PATIENTS AND METHODS:
Three young females, who were diagnosed with hydroureteronephrosis caused by
congenital vesicoureteral junction obstruction, were treated by laparoscopic
ureteral reimplantation with a tunnel underneath the broad ligament. RESULTS:
Surgery was performed successfully without conversion to open surgery. No major
intra- or postoperative complications occurred. Postoperative follow-up was 38,
33 and 26 months, respectively. The operative time was between 220 and 260 min.
The mean estimated blood loss was less than 20 ml. Subsequent imaging performed 3
months after surgery revealed relief of hydroureteronephrosis for all patients.
The patients all gave birth to healthy neonates and showed normal urinary tract
sonogram and urine analysis during the gestation period. CONCLUSION: Laparoscopic
ureteral reimplantation with broad ligament tunnel is safe and effective,
allowing for anatomical reconstruction of ureter defects. However, a larger
clinical sample and longer follow-up period will be needed.
PMID- 25115359
TI - Endoscopic management of high-grade dysplastic Barrett's esophagus with
esophageal varices.
PMID- 25115361
TI - Needle confocal microendoscopy of a pancreatic neuroendocrine tumor.
PMID- 25115360
TI - Prevalence and risk factors for musculoskeletal injuries related to endoscopy.
AB - BACKGROUND: There are limited data regarding work-related injury among
endoscopists. OBJECTIVE: To define the prevalence of endoscopy-related
musculoskeletal injuries and their impact on clinical practice and to identify
physician and practice characteristics associated with their development. DESIGN:
Survey. SETTING: Electronic survey of active members of the American Society for
Gastrointestinal Endoscopy with registered e-mail addresses. PARTICIPANTS:
Physicians who currently or ever performed endoscopy and responded to the survey
between February 2013 and November 2013. INTERVENTION: A 25-question, self
administered, electronic survey. MAIN OUTCOME MEASUREMENTS: Prevalence, location,
and ramifications of work-related injuries and endoscopist characteristics and
workload parameters associated with endoscopy-related injury. RESULTS: The survey
was completed by 684 endoscopists. Of those, 362 (53%) experienced a
musculoskeletal injury perceived definitely (n = 204) or possibly (n = 158)
related to endoscopy. Factors associated with a higher rate of endoscopy-related
injury included higher procedure volume (>20 cases/week; P < .001), greater
number of hours per week spent performing endoscopy (>16 hours/week; P < .001),
and total number of years performing endoscopy (P = .004). The most common sites
of injury were neck and/or upper back (29%) and thumb (28%). Only 55% of injured
endoscopists used practice modifications in response to injuries. Specific
treatments included medications (57%), steroid injection (27%), physiotherapy
(45%), rest (34%), splinting (23%), and surgery (13%). LIMITATIONS: Self-reported
data of endoscopy-related injury. CONCLUSION: Among endoscopists there is a high
prevalence of injuries definitely or potentially related to endoscopy. Higher
procedure volume, more time doing endoscopy per week, and cumulative years
performing endoscopy are associated with more work-related injuries.
PMID- 25115362
TI - Antegrade biopsy by using a trans-catheter technique through EUS-guided
hepaticojejunostomy.
PMID- 25115363
TI - Magnetic resonance enterography, small-intestine contrast US, and capsule
endoscopy to evaluate the small bowel in pediatric Crohn's disease: a
prospective, blinded, comparison study.
AB - BACKGROUND: Small-bowel (SB) disease is a severe clinical entity among the
phenotypes of Crohn's disease (CD). OBJECTIVE: To assess sensitivity,
specificity, and accuracy of magnetic resonance enterography (MRE), small
intestine contrast US (SICUS), and capsule endoscopy (CE) in the diagnosis of
pediatric SB-CD. DESIGN: Prospective, blinded, comparison study. SETTING:
Tertiary center for pediatric inflammatory bowel disease. PATIENTS: Children with
known or suspected CD. Diagnosis of SB obstruction at SICUS or MRE excluded
patients from the study. INTERVENTION: Patients underwent ileocolonoscopy, MRE,
SICUS, and CE over a 7-day period. For the imaging evaluation, SB was divided
into 3 segments: jejunum, proximal and mid ileum, and terminal ileum. MAIN
OUTCOME MEASUREMENTS: The performance of each method was compared to a consensus
reference standard for upper SB and to ileocolonoscopy for the terminal ileum.
RESULTS: Twenty-five patients completed the study. In the jejunum, the
sensitivity of SICUS and CE was 92%, which was not significantly higher than MRE
(75%); the specificity of CE (61%) was significantly lower than that of MRE (P =
.04). In the proximal and mid ileum, MRE and CE did not have significantly higher
sensitivity (100%) than SICUS (80%), but CE was less specific (P > .05). At the
terminal ileum, SICUS and MRE were slightly more sensitive than CE (94% vs. 81%);
however, the latter was more specific. LIMITATIONS: Use of the consensus
reference standard for upper SB. Small number of patients. CONCLUSION: SICUS,
MRE, and CE are all effective options for imaging SB. An integrated use of
different tools should be suggested to achieve a complete assessment of the SB in
children with suspected or confirmed CD.
PMID- 25115364
TI - The Educational Needs of Clinicians Regarding Anticoagulation Therapy for
Prevention of Thromboembolism and Stroke in Patients With Atrial Fibrillation.
AB - The objective is to identify practice patterns and attitudes of and barriers
faced by US physicians assessing thromboembolism/stroke risk and managing
anticoagulation in atrial fibrillation (AF) to determine educational needs. Case
based surveys were used to assess practice patterns, guideline use, barriers, and
attitudes; 51 cardiologists and 50 primary care physicians (PCPs) were surveyed.
Most cardiologists use validated risk scoring systems to assess
thromboembolism/stroke risk, and more than half of PCPs use clinical experience.
Assessment of bleeding risk varied; more than half of respondents rely on
clinical judgment or patient bleeding history. The most commonly used
prophylactic agents are warfarin/another vitamin K antagonist (PCPs) or
antiplatelet agents (cardiologists). Newer anticoagulants are used less
frequently. Bleeding risk, need for frequent monitoring (vitamin K antagonists),
and medication costs were the most significant barriers. Cardiologists and PCPs
could benefit from education on validated scoring systems to assess risk of
thromboembolism/stroke and bleeding in AF, on newly released AF guidelines, and
on newer anticoagulants.
PMID- 25115366
TI - Cage-like effect in Au-Pt nanoparticle synthesis in microemulsions: a simulation
study.
AB - The different distributions of metals in bimetallic nanoparticles synthesized in
microemulsions were studied by computer simulation. The simulations demonstrated
that if the difference between the reduction potentials of both metals is about
0.15-0.3 V, the compartmentalization of the reaction media causes the
accumulation of slower reduction reactants in the microemulsions droplets, which
favours the chemical reaction like a cage effect: increasing the local
concentration of the slower reduction metal salt gives rise to a faster
reduction, so the differences in reduction rates of both metals are attenuated. A
more coincidental reduction of both metals deeply affects the nanoparticle
structure, causing a better mixed alloy. This effect will be more pronounced when
the concentration is higher and the intermicellar exchange rate is faster. This
means that for any fixed microemulsion the nanoparticle structure can be modified
by changing the reactant concentration: the core can be enriched in the faster
reduction metal by lower concentrations, and the shell can be enriched in the
slower metal by higher concentrations. Based on these observations, this study
suggests a route to help experimentalists better create nanoparticles with a pre
defined structure.
PMID- 25115365
TI - Investigation of the role of organic cation transporter 2 (OCT2) in the renal
transport of guanfacine, a selective alpha2A-adrenoreceptor agonist.
AB - 1. Guanfacine is a selective alpha2A-adrenoreceptor agonist primarily excreted as
its unchanged form through urine in human. This study was to investigate the
involvement of organic cation transporter 2 (OCT2) in the renal tubular secretion
of guanfacine. 2. Transport of guanfacine was characterized using human embryonic
kidney (HEK293) cells expressing human OCT2 (hOCT2). The inhibitory effect of
cimetidine on guanfacine uptake was also examined. In addition, in vivo
pharmacokinetic study was conducted in rats to assess the effects of cimetidine
on the pharmacokinetics of guanfacine. 3. The accumulation of guanfacine in hOCT2
transfected HEK293 cells was both time- and concentration-dependent, and markedly
higher than that in mock cells. The apparent Km and Vmax values of guanfacine
uptake by hOCT2 were 96.19 +/- 7.49 MUM and 13.03 +/- 0.49 nmol/mg protein/min,
respectively. Guanfacine transport mediated by hOCT2 was significantly inhibited
by a typical OCT2 inhibitor cimetidine with an IC50 value of 93.82 +/- 1.13 MUM.
Co-administration of cimetidine significantly decreased the plasma clearance
(CLp) as well as the renal clearance (CLr) of guanfacine in rats in a dose
dependent manner, resulting in a noticeable increase in the systemic exposure of
guanfacine. 4. These results indicated that OCT2 may be involved in the renal
disposition of guanfacine.
PMID- 25115367
TI - A new comprehensive classification system for both lower and upper urinary tract
dysfunction in patients with neurogenic bladder.
PMID- 25115368
TI - Use of the Gail model and breast cancer preventive therapy among three primary
care specialties.
AB - BACKGROUND: Breast cancer is an issue of serious concern among women of all ages.
The extent to which providers across primary care specialties assess breast
cancer risk and discuss chemoprevention is unknown. METHODS: Cross-sectional web
based survey completed by 316 physicians in internal medicine (IM), family
medicine (FM), and gynecology (GYN) from February to April of 2012. Survey items
assessed respondents' frequency of use of the Gail model and chemoprevention, and
their attitudes behind practice patterns. Descriptive statistics were used to
generate response distributions, and chi-squared tests were used to compare
responses among specialties. RESULTS: The response rate was 55.0 % (316/575).
Only 40% of providers report having used the Gail model (37% IM, 33% FM, 60% GYN)
and 13% report having recommended or prescribed chemoprevention (9% IM, 8% FM,
30% GYN). Among providers who use the Gail model, a minority use it regularly in
patients who may be at increased breast cancer risk. Among providers who have
prescribed chemoprevention, most have done so five times or fewer. Lack of both
time and familiarity were commonly cited barriers to use of the Gail score and
chemoprevention. CONCLUSIONS: An overall minority of providers, most notably in
FM and IM, use the Gail model to assess, and chemoprevention to decrease, breast
cancer risk. Until providers are more consistent in their use of the Gail model
(or other breast cancer risk calculator) and chemoprevention, opportunities to
intervene in women at increased risk will likely continue to be missed.
PMID- 25115370
TI - Introduction to special issue for World Association for Plastic Surgeons of
Chinese Descent.
PMID- 25115369
TI - Cumulative trauma and midlife well-being in American women who served in Vietnam:
effects of combat exposure and postdeployment social support.
AB - BACKGROUND AND OBJECTIVES: Research increasingly demonstrates that trauma
exposure can have cumulative effects, yet much remains to be learned about
effects of cumulative trauma, particularly regarding longer term adjustment. One
such trauma, combat exposure, is insufficiently understood, especially for women,
who are increasingly engaged in professional combat activities. DESIGN: The study
comprised a cross-sectional survey assessing multiple aspects of current well
being in women approximately 25 years after their service in Vietnam during the
Vietnam War. METHODS: Participants were 1374 women (78% military and 22%
nonmilitary; mean age = 59.7). This study investigated the relations between
three separate categories of trauma exposure (childhood, adulthood, and combat)
and well-being and examined whether perceived social support at return from
Vietnam moderated the association between combat exposure and well-being.
RESULTS: While both childhood and adulthood trauma exposure related to midlife
well-being, combat exposure still uniquely predicted outcomes. Further,
postdeployment perceived social support moderated the association of combat and
well-being: recollected higher perceived social support at homecoming buffered
participants from the links between combat exposure and well-being. CONCLUSIONS:
These results may have important implications for interventions to reduce the
impact of traumatic experiences, particularly in light of the increasing exposure
of women to direct combat events.
PMID- 25115371
TI - Hypertrophic scars and keloids in surgery: current concepts.
AB - Hypertrophic scars and keloids remain a challenge in surgery. We appreciate that
our understanding of the process at cellular and molecular level, profound as it
is, when it comes to the clinical evidence much is left to be desired. Although
the bench to bedside conundrum remains, the science of translational research
calls for an even higher level of cooperation between the scientist and the
clinician for the impetus to succeed.The clinicians alerted us to the possible
theories in the pathogenesis of keloid formation, inter alia, the ischemia
theory, mast cell theory, immune theory, transforming growth factor beta
interaction, mechanical theory, and the melanocyte stimulating hormone theory.
All of the above presupposed a stimulus that would result in an uncontrolled
upregulation of collagen and extracellular matrix expression in the pathogenesis
of the keloid. This bedside to bench initiative, as in true science, realized
more ponderables than possibilities.By the same token, research into the
epidermal-mesenchymal signaling, molecular biology, genomics, and stem cell
research holds much promise in the bench top arena. To assess efficacy, many scar
assessment scores exist in the literature. The clinical measurement of scar
maturity can aid in determining end points for therapeutics. Tissue oxygen
tension and color assessment of scars by standardized photography proved to be
useful.In surgery, the use of dermal substitutes holds some promise as we surmise
that quality scars that arise from dermal elements, molecular and enzyme
behavior, and balance. Although a systematic review shows some benefit for
earlier closure and healing of wounds, no such review exists at this point in
time for the use of dermal substitutes in scars.Adipose-derived stem cell, as it
pertains to scars, will hopefully realize the potential of skin regeneration
rather than by repair in which we are familiar with as well as the undesirable
scarring as a result of healing through the inflammatory response.Translational
research will bear the fruit of coordinating bench to bedside and vice versa in
the interest of progress into the field of regenerative healing that will benefit
the patient who otherwise suffers the myriad of scar complications.
PMID- 25115372
TI - Propranolol promotes accelerated and dysregulated adipogenesis in hemangioma stem
cells.
AB - BACKGROUND: Infantile hemangiomas (IHs) are the most common tumor of infancy, yet
there are no Food and Drug Administration-approved therapeutics to date.
Recently, the nonselective beta-adrenergic-blocker propranolol has been shown to
be a safe and effective means of treating IHs, although its mechanism has yet to
be elucidated. We have previously demonstrated that propranolol induces early and
incomplete adipogenesis in stem cells derived from hemangiomas. We hypothesize
that propranolol promotes dysregulated adipogenesis via the improper regulation
of adipogenic genes. METHODS: Hemangioma stem cells (HemSCs) isolated from
resected IH specimens were treated with adipogenic medium for 1 or 4 days in
either propranolol or vehicle. Cell death was measured by the incorporation of
annexin V and propidium iodide by flow cytometry. Adipogenesis was assessed by
visualizing lipid droplet formation by Oil Red O staining. Proadipogenic genes
C/EBPalpha, C/EBPbeta, C/EBPdelta, PPARdelta, PPARgamma, RXRalpha, and RXRgamma
were analyzed by quantitative reverse transcription and polymerase chain
reaction. RESULTS: Hemangioma stem cells treated with propranolol increased lipid
droplet formation compared to vehicle-treated cells indicating increased
adipogenesis. Cell death as measured by FACS analysis indicated that the
propranolol-treated cells died due to necrosis and not apoptosis. During
adipogenesis, transcript levels of PPARdelta, PPARgamma, C/EBPbeta, and
C/EBPdelta were significantly increased (P<0.01) in propranolol-treated cells
relative to control cells. In contrast, RXRalpha and RXRgamma levels were
significantly decreased (P<0.05), and C/EBPalpha, a gene required for terminal
adipocyte differentiation, was strongly suppressed by propranolol when compared
to vehicle-treated cells (P<0.01). CONCLUSIONS: In HemSCs, propranolol
accelerated dysregulated adipogenic differentiation characterized by improper
adipogenic gene expression. Consistent with accelerated adipogenesis, propranolol
significantly increased the expression of the proadipogenic genes, PPARgamma,
C/EBPbeta, and C/EBPgamma compared to control. However, propranolol treatment
also led to improper induction of PPARdelta and suppression of C/EBPalpha,
RXRalpha, and RXRgamma. Taken together these data indicate that propranolol
promoted dysregulated adipogenesis and inhibited the HemSCs from becoming
functional adipocytes, ultimately resulting in cell death. Understanding this
mechanism behind propranolol's effectiveness will be a vital factor in producing
more effective therapies in the future.
PMID- 25115373
TI - Simultaneous breast reconstruction and treatment of breast cancer-related upper
arm lymphedema with lymphatic lower abdominal flap.
AB - BACKGROUND: This study was designed to introduce the key points about the
transplantation of lower abdominal flap with vascularized lymph node and to
evaluate the effect of breast restoration, breast reconstruction, and lymphatic
transplantation to treat upper limb lymphedema after breast cancer surgery.
MATERIALS AND METHODS: The study was based on the retrospective study on 10 cases
of postmastectomy lymphedema during January 2008 to March 2011. All patients,
aged 36 to 50 years, have had one-side upper-limb lymphedema for 3 to 5 years.
Six patients had accepted radiotherapy. Four patients had a diagnosis of severe
lymphedema, and 2 patients had moderate lymphedema. The isotope radiography
before the operation showed obstruction of lymphatic return, and the
multidetector computed tomography that followed delivered a clear picture of the
abdominal flap blood supply and the blood vessels in the breasts. During the
operation, the scar contracture of the axilla was completely relaxed, and all
patients accepted abdominal transplantation of lower abdominal flap with
vascularized lymph node. After the operation, the elastic bandages were applied
for one year as an adjuvant therapy. The follow-up visits were conducted 1, 3, 6,
and 12 months after the surgery. The measurement indexes included mid-upper arm
circumference, clinical symptoms, and lymphoscintigraphy. RESULTS: All flaps
worked well. One patient was found to have delayed wound healing; one patient saw
no obvious improvement in lymphedema; 7 patients with lymphedema were relieved
with apparent improvement in the affected limbs' mean perimeter and clinical
symptoms; one patient recovered; and another patient was lost to follow-up. The
mean reduction was 2.122+/-2.331 cm, and the reduction of the lymphedematous limb
was statistically significant between the preoperative and 12-month postoperative
groups (P<0.05). The results were good in 4 patients and excellent in one
patient. CONCLUSIONS: The transplantation of abdominal flap with vascularized
lymph node and breast reconstruction, accompanied by the treatment to upper limb
lymphedema and using elastic bandages as an adjuvant therapy, is considered to be
an effective method to restore the configuration and function of breasts. Long
term follow-up visits are undergoing, especially the lymphoscintigraphy, 2 years
after the operation.
PMID- 25115374
TI - Reconstruction for osteoradionecrosis of the mandible: superiority of free iliac
bone flap to fibula flap in postoperative infection and healing.
AB - BACKGROUND: Osteoradionecrosis (ORN) of the mandible is not an uncommon
complication after radiotherapy for head and neck cancers. Although definitive
treatment has been confirmed as radical excision of the necrotic bone with
simultaneous vascularized osteocutaneous flap reconstruction, it remains a unique
challenge. In this study, we compare our results of reconstruction with free
iliac and fibula flaps in flap survival, bony union, and postoperative
complications. PATIENTS AND METHODS: From 1986 to 2011, there were 153 mandibular
ORN cases in our center that were treated with radical resection of the necrotic
bone and reconstruction with either vascularized iliac (n=108) or fibula flaps
(n=45). Data collected for analysis included patient demographics, flap survival
rate, postoperative infection rate, nonunion/malunion rate, mean hospital stay,
and antibiotics use. RESULTS: All patients healed eventually without recurrence
of ORN. However, we observed difference in the complication rate between the
iliac flap group and fibula flap group. In the group with iliac flap
reconstruction, patients required less days of hospital stay for intravenous
antibiotics treatment postoperatively. The average days required for intravenous
antibiotics in the iliac flap group were 10.46 (2.28) versus 16.09 (3.88) days in
the fibula group (P<0.01). In the group with fibula flap reconstruction, 9
(20.0%) patients had subsequent neck infection due to healing problem, compared
to 8 (7.4%) patients in the iliac flap group (P=0.04). In the iliac flap group,
the nonunion and malunion rates were 4.6% and 2.8% respectively; whereas in the
fibula group, the rates were 15.5% and 6.6%, respectively (P=0.04 and 0.36,
respectively). CONCLUSIONS: For ORN patients, vascularized iliac bone flap
provides more reliable results compared to fibula flap. The merits of
vascularized iliac flap include the following: (1) its natural curve mimics the
shape of mandible and does not need osteotomy; (2) it offers more volume of bone
that matches better to the native mandible to allow later osteointegration as
well as faster bony union, due to the nature of being a membranous bone; and (3)
it carries more abundant soft tissue to obliterate possible dead space. The only
disadvantages are short pedicle and requiring special management of skin paddle,
which can be overcome by training in microsurgery.
PMID- 25115375
TI - Penile reconstruction by preexpanded free scapular flap in severely burned
patient.
AB - BACKGROUND: Penile reconstruction or phalloplasty has always been one of the most
challenging problems for plastic surgeons. In 1936, Bogoras performed the first
phalloplasty by using traditional tubed pedicle flaps. Many other flaps and
methods have been applied since, including lower abdominal flaps, pudendal-thigh
flaps, parascapular flaps, paraumbilical flaps and, of course, radial forearm
flaps. For each method, reports of both functional and esthetic successes abound.
In this case, donor sites for phalloplasty were somewhat limited by the severe
electric burn injury. After much consideration, we decided to preexpand the
scapular flap and to use this for phalloplasty, with satisfactory outcome. Our
case is a 31-year-old patient who sustained a 19% total burn surface area by
electrical burn in August 2011. The burn area involved both forearms, abdominal
region, both femoral regions, and perineum including genitalia loss. Most of the
burn wounds were skin grafted shortly after the injury. Due to the nature of the
burn, regular donor sites for penile reconstruction were unavailable. Before
surgery, we went through a detailed plan for phalloplasty with the patient and
his family. The patient consented to the 2-stage surgery for the penile
reconstruction. The first stage was insertion of a 600-mL soft tissue expander in
the scapular region. After 4 months of expansion, the second stage of free
scapular flap transfer was performed in March 2012. RESULTS: The reconstruction
was successful with good appearance and patient satisfaction, complicated by
urethral fistula. Eight months later, the urinary fistula was repaired
successfully. CONCLUSIONS: The free scapular flap proved to be an ideal solution
to this patient's dilemma. The flap has adequate amount of tissue and a reliable
blood supply. Its amenability to be expanded allows better donor-site primary
closure. Tissue bulk resulted in adequate stiffness without artificial prosthesis
for the phallus to be functional.
PMID- 25115376
TI - Angioarchitecture of extracranial arteriovenous malformations: a vascular casting
study.
AB - PURPOSE: Arteriovenous malformations (AVMs) are congenital vascular anomalies,
not proliferative neoplasms, but tend to behave aggressively with unpredictable
growth and tissue destruction. For the understanding of the angioarchitecture of
extracranial AVM, which is believed to be the main cause that explains all
presenting symptoms, the study aimed to elucidate the vascular structure of
extracranial AVM with vascular cast of completely excised AVM lesion. METHODS:
From 1996 to 2011, a total of 289 cases with extracranial AVM received surgical
or surgery-based treatment by the authors in the department, excluding cases that
received embolization alone. Among them, 10 patients (4 female cases, 6 male
cases) were involved in this study. All the AVM nidi were excised and injected
with resin through feeding arteries, then the corrosion casts were made for
dimensional measurement. RESULTS: Arteriovenous malformation nidus was comprised
of multilevel branched blood vessels. We measured the diameter of predominant
trunk and primary level branch vessels. The diameter of predominant trunk ranged
from 2.0 (0.2) to 4.3 (0.2) mm, whereas primary level branch vessels from 1.0
(0.1) to 2.0 (0.2) mm. Seventy percent of AVM casts included trunk blood vessels
with the maximal diameters ranged from 4 to 12 mm, and an average of 7.0 mm (SD,
0.93; n=10). In this series, the smallest blood vessel visible in the cast was
approximately 0.2 mm in diameter, whereas balloon-like serious dilated vessels
from 10.2 to 25.4 mm. CONCLUSIONS: Vascular casting study shows us more
informative, realistic, and objective 3-dimensional angioarchitecture than
digital subtract angiography, 3-dimensional computed tomography angiography, and
magnetic resonance angiography, not only for the facilitation of treatment
decision but also for the purpose of education and research.
PMID- 25115377
TI - Expansion method in secondary total ear reconstruction for undesirable
reconstructed ear.
AB - BACKGROUND: Ear reconstruction by autologous costal cartilage grafting is the
most widely applied technique with fewer complications. However, undesirable ear
reconstruction brings more problems to plastic surgeons. Some authors resort to
free flap or osseointegration technique with prosthetic ear. In this article, we
introduce a secondary total ear reconstruction with expanded skin flap method.
METHODS: From July 2010 to April 2012, 7 cases of undesirable ear reconstruction
were repaired by tissue expansion method. Procedures including removal of
previous cartilage framework, soft tissue expander insertion, and second stage of
cartilage framework insertion were performed to each case regarding their local
conditions. RESULTS: The follow-up time ranged from 6 months to 2.5 years. All of
the cases recovered well with good 3-dimensional forms, symmetrical
auriculocephalic angle, and stable fixation. CONCLUSIONS: All these evidence
showed that this novel expansion method is safe, stable, and less traumatic for
secondary total ear reconstruction. With sufficient expanded skin flap and
refabricated cartilage framework, lifelike appearance of reconstructed ear could
be acquired without causing additional injury.
PMID- 25115378
TI - Masseter-to-facial nerve transfer: a highly effective technique for facial
reanimation after acoustic neuroma resection.
AB - BACKGROUND: Masseter-to-facial nerve transfer is a new procedure for patients who
acquire a proximal injury to the facial nerve. This article reports that this
procedure is effective and associated with minimal morbidities. METHODS: From
November 2010 to February 2013, 16 patients underwent a masseter-to-facial nerve
transfer. Their denervation periods varied from 2 to 18 months, with an average
of 10.1+/-4.1 months. Their ages varied from 22 to 70 years, with an average of
34.7+/-15.4 years. The etiology of denervation was tumor resection in the
cerebellopontine angle in all cases. All of the patients were followed up several
times. The outcomes of the first follow-up at 3 months postoperatively and the
last follow-up at a minimum 12 months postoperatively were documented. Using
Terzis' and Metha's scales, the smile outcomes and synkinetic movements as
visualized using standardized videos were graded preoperatively and
postoperatively. The periods between the operation and the onset of mimetic
muscle contraction were documented. A questionnaire was administered to evaluate
the donor-site morbidity and the ability to smile without biting. RESULTS: The
final outcomes for smile function were as follows: 9 patients (56.3%) had
excellent or good function, 5 patients (31.3%) had moderate function, and 2
patients (12.5%) had poor function. There was significant improvement between the
preoperative and postoperative time points and between the outcomes at the first
and last follow-ups (P<0.05). Additionally, 13 (81.3%) patients had the ability
to smile without biting 12 months postoperatively. The onset of muscle motion
varied from 56 to 365 days and was positively correlated with age in the group of
patients older than 40 years and negatively correlated with the outcome of the
first follow-up. Four (25%) patients complained of concavity at the
parotideomasseteric region, but none complained of disturbance in food intake.
Synkinetic movements were observed in all patients and were rated as mild.
CONCLUSIONS: The masseter-facial nerve transfer effectively reanimated the
paralytic muscle in patients who acquired an intracranial facial nerve injury
with minimal deficits at the donor site. After continued physical therapy, some
patients were able to regain a symmetrical and effortless smile with mild
synkinetic movements.
PMID- 25115380
TI - Clinical phenotype network: the underlying mechanism for personalized diagnosis
and treatment of traditional Chinese medicine.
AB - Traditional Chinese medicine (TCM) investigates the clinical diagnosis and
treatment regularities in a typical schema of personalized medicine, which means
that individualized patients with same diseases would obtain distinct diagnosis
and optimal treatment from different TCM physicians. This principle has been
recognized and adhered by TCM clinical practitioners for thousands of years.
However, the underlying mechanisms of TCM personalized medicine are not fully
investigated so far and remained unknown. This paper discusses framework of TCM
personalized medicine in classic literatures and in real-world clinical settings,
and investigates the underlying mechanisms of TCM personalized medicine from the
perspectives of network medicine. Based on 246 well-designed outpatient records
on insomnia, by evaluating the personal biases of manifestation observation and
preferences of herb prescriptions, we noted significant similarities between each
herb prescriptions and symptom similarities between each encounters. To
investigate the underlying mechanisms of TCM personalized medicine, we
constructed a clinical phenotype network (CPN), in which the clinical phenotype
entities like symptoms and diagnoses are presented as nodes and the correlation
between these entities as links. This CPN is used to investigate the promiscuous
boundary of syndromes and the co-occurrence of symptoms. The small-world
topological characteristics are noted in the CPN with high clustering structures,
which provide insight on the rationality of TCM personalized diagnosis and
treatment. The investigation on this network would help us to gain understanding
on the underlying mechanism of TCM personalized medicine and would propose a new
perspective for the refinement of the TCM individualized clinical skills.
PMID- 25115379
TI - Phospholipid binding residues of eukaryotic membrane-remodelling F-BAR domain
proteins are conserved in Helicobacter pylori CagA.
AB - BACKGROUND: Cytotoxin associated gene product A (CagA) is an oncogenic protein
secreted by the gastric bacterium Helicobacter pylori. Internalization of CagA by
human epithelial cells occurs by an unknown mechanism that requires interaction
with the host membrane lipid phosphatidylserine. FINDINGS: Local homology at the
level of amino acid sequence and secondary structure has been identified between
the membrane-tethering region of CagA and the lipid-binding Fes-CIP4 homology
Bin/Amphiphysin/Rvs (F-BAR) domains of eukaryotic proteins. The F-BAR proteins
are major components of the endocytic machinery. In addition to the membrane
binding F-BAR domains, they contain other domains that interact with actin
regulatory networks and mediate interplay between membrane dynamics and
cytoskeleton re-arrangements. Positively charged residues found on the lipid
binding face of the F-BAR domains are conserved in CagA and represent residues
involved in CagA binding to lipids. CONCLUSIONS: The homologies with F-BAR
proteins extend to lipid binding specificities and involvement in reorganization
of the actin cytoskeleton. CagA and F-BAR domains share binding specificity for
phosphatidylserine and phosphoinositides. Similar to the F-BAR proteins, CagA has
a membrane-binding module and a module that shares structural homology with actin
binding proteins, and, like eukaryotic F-BAR domain proteins, CagA function is
linked to actin dynamics. The uncovered similarities between the bacterial
effector protein and eukaryotic F-BAR proteins suggest convergent evolution of
CagA towards a similar function.
PMID- 25115381
TI - In vivo evaluation of two forms of urea in the skin by Raman spectroscopy after
application of urea-containing cream.
AB - BACKGROUND/PURPOSE: As urea is one of the natural moisturizing factor (NMF)
components in the stratum corneum, it has been used in topical products to
improve skin conditions. However, the penetration behavior of urea in the skin
after application of urea-containing cream has not been determined as there has
been no technique with which to measure the urea content in the skin in vivo non
invasively. We therefore applied Raman spectroscopy to evaluate the depth profile
of urea content in the skin. We investigated changes in depth profiles of two
forms of urea to evaluate the penetration behavior of urea after application of
urea-containing cream. METHODS: Commercially available moisturizing creams F and
R in quantities of 2.2-mg/cm(2) and containing 20% (w/w) urea were applied to
volar forearm skin of six Japanese subjects. Raman spectra of the skin were
measured at 2-MUm intervals from the skin surface toward the interior using a
confocal Raman spectrometer (model 3510 SCA) before and 15, 60, and 120 min after
the application of the creams. The amounts of the two forms of urea, urea in
water solution and urea in a solid state, were calculated by adding the spectra
of solid urea and the cream base to a previously reported algorithm including the
spectrum of urea in water solution. RESULTS: The characteristic band of urea in
water solution was observed at approximately 1004/cm and that of the solid state
at approximately 1010/cm in the Raman spectra of the skin after application of
either cream. There was more urea in water solution form in the area where cream
F was applied than in the area where cream R was applied. There was more urea in
a solid state in the area where cream R was applied than in the area where cream
F was applied at all depths and measurement times. In particular, there was
significantly more urea in a solid state below a depth of 2 MUm in the area where
cream R was applied than in the area where cream F was applied 15 min after
application. CONCLUSION: The present study demonstrated that we can measure both
urea forms in the skin after the application of urea-containing creams. The
proposed technique would be useful in the evaluation of characteristics of the
penetration behavior of urea in the skin after the application of various urea
containing moisturizers.
PMID- 25115383
TI - FGFR1 activation is an escape mechanism in human lung cancer cells resistant to
afatinib, a pan-EGFR family kinase inhibitor.
AB - Most NSCLC patients with EGFR mutations benefit from treatment with EGFR-TKIs,
but the clinical efficacy of EGFR-TKIs is limited by the appearance of drug
resistance. Multiple kinase inhibitors of EGFR family proteins such as afatinib
have been newly developed to overcome such drug resistance. We established
afatinib-resistant cell lines after chronic exposure of activating EGFR mutation
positive PC9 cells to afatinib. Afatinib-resistant cells showed following
specific characteristics as compared to PC9: [1] Expression of EGFR family
proteins and their phosphorylated molecules was markedly downregulated by
selection of afatinib resistance; [2] Expression of FGFR1 and its ligand FGF2 was
alternatively upregulated; [3] Treatment with anti-FGF2 neutralizing antibody
blocked enhanced phosphorylation of FGFR in resistant clone; [4] Both resistant
clones showed collateral sensitivity to PD173074, a small-molecule FGFR-TKIs, and
treatment with either PD173074 or FGFR siRNA exacerbated suppression of both
afatinib-resistant Akt and Erk phosphorylation when combined with afatinib; [5]
Expression of twist was markedly augmented in resistant sublines, and twist
knockdown specifically suppressed FGFR expression and cell survival. Together,
enhanced expression of FGFR1 and FGF2 thus plays as an escape mechanism for cell
survival of afatinib-resistant cancer cells, that may compensate the loss of EGFR
driven signaling pathway.
PMID- 25115382
TI - HDAC inhibitors and immunotherapy; a double edged sword?
AB - Epigenetic modifications, like histone acetylation, are essential for regulating
gene expression within cells. Cancer cells acquire pathological epigenetic
modifications resulting in gene expression patterns that facilitate and sustain
tumorigenesis. Epigenetic manipulation therefore is emerging as a novel targeted
therapy for cancer. Histone Acetylases (HATs) and Histone Deacetylases (HDACs)
regulate histone acetylation and hence gene expression. Histone deacetylase
(HDAC) inhibitors are well known to affect cancer cell viability and biology and
are already in use for the treatment of cancer patients. Immunotherapy can lead
to clinical benefit in selected cancer patients, especially in patients with
limited disease after tumor debulking. HDAC inhibitors can potentially synergize
with immunotherapy by elimination of tumor cells. The direct effects of HDAC
inhibitors on immune cell function, however, remain largely unexplored. Initial
data have suggested HDAC inhibitors to be predominantly immunosuppressive, but
more recent reports have challenged this view. In this review we will discuss the
effects of HDAC inhibitors on tumor cells and different immune cell subsets,
synergistic interactions and possible mechanisms. Finally, we will address future
challenges and potential application of HDAC inhibitors in immunocombination
therapy of cancer.
PMID- 25115384
TI - A 5-gene classifier from the carcinoma-associated fibroblast transcriptomic
profile and clinical outcome in colorectal cancer.
AB - Based on 108 differentially expressed genes between carcinoma-associated
fibroblasts (CAFs) and paired normal colonic fibroblasts we recently reported, a
5-gene classifier for relapse prediction in Stage II/III colorectal cancer (CRC )
was developed. Its predictive value was validated in datasets GSE17538, GSE33113
and GSE14095. An additional validation was performed in a metacohort (n=317) and
142 CRC patients by means of RT-PCR. The 5-gene classifier was significantly
associated with increased relapse risk and death from CRC across all validation
series of Stage II/III patients used. Multivariate Cox regression analyses
confirmed the independent prognostic value of the stromal classifier (HR=2.67;
P=0.002). Post-test probabilities provided evidence of the suitability of the 5
gene classifier in clinical practice, identifying a subgroup of Stage-II patients
who were at high risk of relapse. Moreover, the a priory worst prognosis
mesenchymal subtype of tumours can be stratified according to the physiological
status of their carcinoma-associated fibroblasts. In conclusion the CAFs-derived
5-gene classifier provides more accurate information about outcome than
conventional clinicopathological criteria and it could be useful to take clinical
decisions, especially in Stage II. Additionally, the classifier put into
relevance the CAF's intratumoral heterogeneity and might contribute to find
relevant targets for depleting adequate CAFS subtypes.
PMID- 25115385
TI - T cell-recruiting triplebody 19-3-19 mediates serial lysis of malignant B
lymphoid cells by a single T cell.
AB - Triplebody 19-3-19, an antibody-derived protein, carries three single chain
fragment variable domains in tandem in a single polypeptide chain. 19-3-19 binds
CD19-bearing lymphoid cells via its two distal domains and primary T cells via
its CD3-targeting central domain in an antigen-specific manner. Here, malignant B
lymphoid cell lines and primary cells from patients with B cell malignancies were
used as targets in cytotoxicity tests with pre-stimulated allogeneic T cells as
effectors. 19-3-19 mediated up to 95 % specific lysis of CD19-positive tumor
cells and, at picomolar EC50 doses, had similar cytolytic potency as the
clinically successful agent Blinatumomab. 19-3-19 activated resting T cells from
healthy unrelated donors and mediated specific lysis of both autologous and
allogeneic CD19-positive cells. 19-3-19 led to the elimination of 70 % of CD19
positive target cells even with resting T cells as effectors at an effector-to
target cell ratio of 1 : 10. The molecule is therefore capable of mediating
serial lysis of target cells by a single T cell. These results highlight that
central domains capable of engaging different immune effectors can be
incorporated into the triplebody format to provide more individualized therapy
tailored to a patient's specific immune status.
PMID- 25115387
TI - Targeted ultra-deep sequencing reveals recurrent and mutually exclusive mutations
of cancer genes in blastic plasmacytoid dendritic cell neoplasm.
AB - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematopoietic
malignancy characterized by dismal prognosis and overall poor therapeutic
response. Since the biology of BPDCN is barely understood, our study aims to shed
light on the genetic make-up of these highly malignant tumors. Using targeted
high-coverage massive parallel sequencing, we investigated 50 common cancer genes
in 33 BPDCN samples. We detected point mutations in NRAS (27.3% of cases), ATM
(21.2%), MET, KRAS, IDH2, KIT (9.1% each), APC and RB1 (6.1%), as well as in VHL,
BRAF, MLH1, TP53 and RET1 (3% each). Moreover, NRAS-, KRAS- and ATM-mutations
were found to be mutually exclusive and we observed recurrent mutations in NRAS,
IDH2, APC and ATM. CDKN2A deletions were detected in 27.3% of the cases followed
by deletions of RB1 (9.1%), PTEN and TP53 (3% each). The mutual exclusive
distribution of some mutations may point to different subgroups of BPDCN whose
biological significance remains to be explored.
PMID- 25115388
TI - The stress phenotype makes cancer cells addicted to CDT2, a substrate receptor of
the CRL4 ubiquitin ligase.
AB - CDT2/L2DTL/RAMP is one of the substrate receptors of the Cullin Ring Ubiquitin
Ligase 4 that targets for ubiquitin mediated degradation a number of substrates,
such as CDT1, p21 and CHK1, involved in the regulation of cell cycle and
survival. Here we show that CDT2 depletion was alone able to induce the apoptotic
death in 12/12 human cancer cell lines from different tissues, regardless of the
mutation profile and CDT2 expression level. Cell death was associated to
rereplication and to loss of CDT1 degradation. Conversely, CDT2 depletion did not
affect non-transformed human cells, such as immortalized kidney, lung and breast
cell lines, and primary cultures of endothelial cells and osteoblasts. The
ectopic over-expression of an activated oncogene, such as the mutation-activated
RAS or the amplified MET in non-transformed immortalized breast cell lines and
primary human osteoblasts, respectively, made cells transformed in vitro,
tumorigenic in vivo, and susceptible to CDT2 loss. The widespread effect of CDT2
depletion in different cancer cells suggests that CDT2 is not in a synthetic
lethal interaction to a single specific pathway. CDT2 likely is a non-oncogene to
which transformed cells become addicted because of their enhanced cellular
stress, such as replicative stress and DNA damage.
PMID- 25115386
TI - Cannabinoids as therapeutic agents in cancer: current status and future
implications.
AB - The pharmacological importance of cannabinoids has been in study for several
years. Cannabinoids comprise of (a) the active compounds of the Cannabis sativa
plant, (b) endogenous as well as (c) synthetic cannabinoids. Though cannabinoids
are clinically used for anti-palliative effects, recent studies open a promising
possibility as anti-cancer agents. They have been shown to possess anti
proliferative and anti-angiogenic effects in vitro as well as in vivo in
different cancer models. Cannabinoids regulate key cell signaling pathways that
are involved in cell survival, invasion, angiogenesis, metastasis, etc. There is
more focus on CB1 and CB2, the two cannabinoid receptors which are activated by
most of the cannabinoids. In this review article, we will focus on a broad range
of cannabinoids, their receptor dependent and receptor independent functional
roles against various cancer types with respect to growth, metastasis, energy
metabolism, immune environment, stemness and future perspectives in exploring new
possible therapeutic opportunities.
PMID- 25115389
TI - Identification of a gene expression driven progression pathway in myxoid
liposarcoma.
AB - AIM: to investigate the events involved in the progression of myxoid liposarcoma
(MLS). Gene expression profiling and immunohistochemical/biochemical analyses
were applied to specimens representative of the opposite ends of the MLS
spectrum: pure myxoid (ML) and pure round cell (RC) liposarcomas. The analyses
revealed the involvement of both coding and non coding RNAs (SNORDs located in
DLK1-DIO3 region) and support a model of stepwise progression mainly driven by
epigenetic changes involving tumour vascular supply and tumoral cellular
component. In this model, a switch in the vascular landscape from a normal to a
pro-angiogenic signature and the silencing of DLK1-DIO3 region mark the
progression from ML to RC in concert with the acquisition by the latter of the
over-expression of YYI/C-MYC/HDAC2, together with over-expression of genes
involved in cell proliferation and stemness: MKNK2, MSX1 and TRIM71. Taken
together, these findings strongly suggest that to progress from ML to RC
liposarcoma the cells have to overcome the epigenetic silencing restriction point
in order to reset their new stem-like differentiation signature. Our findings
provide a first attempt at identifying the missing links between ML and RC
liposarcomas, that may also have broader applications in other clinico
pathological settings characterised by a spectrum of progression.
PMID- 25115391
TI - 4EGI-1 targets breast cancer stem cells by selective inhibition of translation
that persists in CSC maintenance, proliferation and metastasis.
AB - Cancer death is a leading cause of global mortality. An estimated 14.1 million
new cancer cases and 8.2 million cancer deaths occurred worldwide in 2012 alone.
Cancer stem cells (CSCs) within tumors are essential for tumor metastasis and
reoccurrence, the key factors of cancer lethality. Here we report that 4EGI-1, an
inhibitor of the interaction between translation initiation factors eIF4E1 and
eIF4G1 effectively inhibits breast CSCs through selectively reducing translation
persistent in breast CSCs. Translation initiation factor eIF4E1 is significantly
enhanced in breast CSCs in comparison to non-CSC breast cancer cells. 4EGI-1
presents increased cytotoxicity to breast CSCs compared to non-CSC breast cancer
cells. 4EGI-1 promotes breast CSC differentiation and represses breast CSC
induced tube-like structure formation of human umbilical vein endothelial cells
(HUVECs). 4EGI-1 isomers suppress breast CSC tumorangiogenesis and tumor growth
in vivo. In addition, 4EGI-1 decreases proliferation in and induces apoptosis
into breast CSC tumor cells. Furthermore, 4EGI-1 selectively inhibits translation
of mRNAs encoding NANOG, OCT4, CXCR4, c-MYC and VEGF in breast CSC tumors. Our
study demonstrated that 4EGI-1 targets breast CSCs through selective inhibition
of translation critical for breast CSCs, suggesting that selective translation
initiation interference might be an avenue targeting CSCs within tumors.
PMID- 25115390
TI - The role of homeostatic regulation between tumor suppressor DAB2IP and oncogenic
Skp2 in prostate cancer growth.
AB - Altered DAB2IP gene expression often detected in prostate cancer (PCa) is due to
epigenetic silencing. In this study, we unveil a new mechanism leading to the
loss of DAB2IP protein; an oncogenic S-phase kinase-associated protein-2 (Skp2)
as E3 ubiquitin ligase plays a key regulator in DAB2IP degradation. In order to
unveil the role of Skp2 in the turnover of DAB2IP protein, both prostate cell
lines and prostate cancer specimens with a variety of molecular and cell biologic
techniques were employed. We demonstrated that DAB2IP is regulated by Skp2
mediated proteasome degradation in the prostate cell lines. Further analyses
identified the N-terminal DAB2IP containing the ubiquitination site.
Immunohistochemical study exhibited an inverse correlation between DAB2IP and
Skp2 protein expression in the prostate cancer tissue microarray. In contrast,
DAB2IP can suppressSkp2 protein expression is mediated through Akt signaling. The
reciprocal regulation between DAB2IP and Skp2 can impact on the growth of PCa
cells. This reciprocal regulation between DAB2IP and Skp2 protein represents a
unique homeostatic balance between tumor suppressor and oncoprotein in normal
prostate epithelia, which is apparently altered in cancer cells. The outcome of
this study has identified new potential targets for developing new therapeutic
strategy for PCa.
PMID- 25115392
TI - F-box protein FBXO31 is down-regulated in gastric cancer and negatively regulated
by miR-17 and miR-20a.
AB - FBXO31, a subunit of the SCF ubiquitin ligase, played a crucial role in neuronal
development, DNA damage response and tumorigenesis. Here, we investigated the
expression and prognosis value of FBXO31 in human primary gastric cancer (GC)
samples. Meanwhile, the biological role and the regulation mechanism of FBXO31
were evaluated. We found that FBXO31 mRNA and protein was decreased dramatically
in the GC tissue compared with the adjacent non-cancerous tissues. FBXO31
expression was significantly associated with tumor size, tumor infiltration,
clinical grade and patients' prognosis. FBXO31 overexpression significantly
decreased colony formation and induced a G1-phase arrest and inhibited the
expression of CyclinD1 protein in GC cells. Further evidence was obtained from
knockdown of FBXO31. Ectopic expression of FBXO31 dramatically inhibited
xenograft tumor growth in nude mice. miR-20a and miR-17 mimics inhibited, whereas
the inhibitor of miR-20a and miR-17 increased, the expression of FBXO31,
respectively. miR-20a and miR-17 directly bind to the 3'-UTR of FBXO31. The level
of miR-20a and miR-17 in GC tissue was significantly higher than that in
surrounding normal mucosa. Moreover, a highly significant negative correlation
between miR-20a (miR-17) and FBXO31 was observed in these GC samples. Therefore,
effective therapy targeting the miR-20a (miR-17)-FBXO31-CyclinD1 pathway may help
control GC progression.
PMID- 25115394
TI - Circulating miR-182 is a biomarker of colorectal adenocarcinoma progression.
AB - MiR-182 expression was evaluated by qRT-PCR and in situ hybridization in 20
tubular adenomas, 50 colorectal carcinoma (CRC), and 40 CRC liver metastases.
Control samples obtained from patients with irritable bowel syndrome, or tumor
matched normal colon mucosa were analyzed (n=50). MiR-182 expression increased
progressively and significantly along with the colorectal carcinogenesis cascade,
and in CRC liver metastases. The inverse relation between miR-182 and the
expression of its target gene ENTPD5 was investigated by immunohistochemical
analysis. We observed that normal colocytes featured a strong ENTPD5 cytoplasmic
expression whereas a significantly and progressively lower expression was present
along with dedifferentiation of the histologic phenotype. Plasma samples from 51
CRC patients and controls were tested for miR-182 expression. Plasma miR-182
concentrations were significantly higher in CRC patients than in healthy controls
or patients with colon polyps at endoscopy. Moreover, miR-182 plasma levels were
significantly reduced in post-operative samples after radical hepatic
metastasectomy compared to preoperative samples. Our results strengthen the
hypothesis of a central role of miR-182 dysregulation in colon mucosa
transformation, demonstrate the concomitant progressive down-regulation of ENTPD5
levels during colon carcinogenesis, and indicate the potential of circulating miR
182 as blood based biomarker for screening and monitoring CRC during the follow
up.
PMID- 25115395
TI - Aurora kinase a suppresses metabolic stress-induced autophagic cell death by
activating mTOR signaling in breast cancer cells.
AB - Aberrant Aur-A signaling is associated with tumor malignant behaviors. However,
its involvement in tumor metabolic stress is not fully elucidated. In the present
study, prolonged nutrient deprivation was conducted into breast cancer cells to
mimic metabolic stress in tumors. In these cells, autophagy was induced, leading
to caspase-independent cell death, which was blocked by either targeted knockdown
of autophagic gene ATG5 or autophagy inhibitor 3-Methyladenine (3-MA). Aur-A
overexpression mediated resistance to autophagic cell death and promoted breast
cancer cells survival when exposed to metabolic stress. Moreover, we provided
evidence that Aur-A suppressed autophagy in a kinase-dependent manner.
Furthermore, we revealed that Aur-A overexpression enhanced the mammalian target
of rapamycin (mTOR) activity under metabolic stress by inhibiting glycogen
synthase kinase 3beta (GSK3beta). Inhibition of mTOR activity by rapamycin
sensitized Aur-A-overexpressed breast cancer cells to metabolic stress-induced
cell death. Consistently, we presented an inverse correlation between Aur-A
expression (high) and autophagic levels (low) in clinical breast cancer samples.
In conclusion, our data provided a novel insight into the cyto-protective role of
Aur-A against metabolic stress by suppressing autophagic cell death, which might
help to develop alternative cell death avenues for breast cancer therapy.
PMID- 25115396
TI - The microRNA-23b/27b/24-1 cluster is a disease progression marker and tumor
suppressor in prostate cancer.
AB - Our recent study of microRNA (miRNA) expression signatures in prostate cancer
(PCa) has revealed that all members of the miR-23b/27b/24-1 cluster are
significantly downregulated in PCa tissues. The aim of this study was to
investigate the effectiveness of these clustered miRNAs as a disease progression
marker and to determine the functional significance of these clustered miRNAs in
PCa. Expression of the miR-23b/27b/24-1 cluster was significantly reduced in PCa
tissues. Kaplan-Meier survival curves showed that low expression of miR-27b
predicted a short duration of progression to castration-resistant PCa. Gain-of
function studies using mature miR-23b, miR-27b,and miR-24-1 significantly
inhibited cell proliferation, migration and invasion in PCa cells (PC3 and
DU145). To identify the molecular targets of these miRNAs, we carried out gene
expression and in silico database analyses. GOLM1 was directly regulated by miR
27b in PCa cells. Elucidation of the molecular targets and pathways regulated by
the tumor-suppressive microRNAs should shed light on the oncogenic and metastatic
processes in PCa.
PMID- 25115393
TI - The miR-124-prolyl hydroxylase P4HA1-MMP1 axis plays a critical role in prostate
cancer progression.
AB - Collagen prolyl hydroxylases (C-P4HAs) are a family of enzymes involved in
collagen biogenesis. One of the isoforms of P4HA, Prolyl 4-hydroxylase, alpha
polypeptide I (P4HA1), catalyzes the formation of 4-hydroxyproline that is
essential for the proper three-dimensional folding of newly synthesized
procollagen chains. Here, we show the overexpression of P4HA1 in aggressive
prostate cancer. Immunohistochemical analysis using tissue microarray
demonstrated that P4HA1 expression was correlated with prostate cancer
progression. Using in vitro studies, we showed that P4HA1 plays a critical role
in prostate cancer cell growth and tumor progression. Expression profiling
studies using P4HA1 modulated prostate cells suggested regulation of Matrix
metalloproteases 1. The invasive properties of P4HA1 overexpressing cells were
reversed by blocking MMP1. Our studies indicate P4HA1 copy number gain in a
subset of metastatic prostate tumors and its expression is also regulated by
microRNA-124. MiR-124 in turn is negatively regulated by transcriptional
repressors EZH2 and CtBP1, both of which are overexpressed in aggressive prostate
cancer. Chick chorioallantoic membrane (CAM) assay and mice xenograft
investigations show that P4HA1 is required for tumor growth and metastasis in
vivo. Our observations suggest that P4HA1 plays a critical role in prostate
cancer progression and could serve as a viable therapeutic target.
PMID- 25115397
TI - EZH2 dependent H3K27me3 is involved in epigenetic silencing of ID4 in prostate
cancer.
AB - Inhibitor of DNA binding/differentiation protein 4 (ID4) is dominant negative
helix loop helix transcriptional regulator is epigenetically silenced due to
promoter hyper-methylation in many cancers including prostate. However, the
underlying mechanism involved in epigenetic silencing of ID4 is not known. Here,
we demonstrate that ID4 promoter methylation is initiated by EZH2 dependent tri
methylation of histone 3 at lysine 27 (H3K27me3). ID4 expressing (LNCaP) and non
expressing (DU145 and C81) prostate cancer cell lines were used to investigate
EZH2, H3K27me3 and DNMT1 enrichment on ID4 promoter by Chromatin immuno
precipitation (ChIP). Enrichment of EZH2, H3K27Me3 and DNMT1 in DU145 and C81
cell lines compared to ID4 expressing LNCaP cell line. Knockdown of EZH2 in DU145
cell line led to re-expression of ID4 and decrease in enrichment of EZH2,
H3K27Me3 and DNMT1 demonstrating that ID4 is regulated in an EZH2 dependent
manner. ChIP data on prostate cancer tissue specimens and cell lines suggested
EZH2 occupancy and H3K27Me3 marks on the ID4 promoter. Collectively, our data
indicate a PRC2 dependent mechanism in ID4 promoter silencing in prostate cancer
through recruitment of EZH2 and a corresponding increase in H3K27Me3. Increased
EZH2 but decreased ID4 expression in prostate cancer strongly supports this
model.
PMID- 25115398
TI - Fructose-2,6-bisphosphate synthesis by 6-phosphofructo-2-kinase/fructose-2,6
bisphosphatase 4 (PFKFB4) is required for the glycolytic response to hypoxia and
tumor growth.
AB - Fructose-2,6-bisphosphate (F2,6BP) is a shunt product of glycolysis that
allosterically activates 6-phosphofructo-1-kinase (PFK-1) resulting in increased
glucose uptake and glycolytic flux to lactate. The F2,6BP concentration is
dictated by four bifunctional 6-phosphofructo-2-kinase/fructose-2,6
bisphosphatases (PFKFB1-4) with distinct kinase:phosphatase activities. PFKFB4 is
over-expressed in human cancers, induced by hypoxia and required for survival and
growth of several cancer cell lines. Although PFKFB4 appears to be a rational
target for anti-neoplastic drug development, it is not clear whether its kinase
or phosphatase activity is required for cancer cell survival. In this study, we
demonstrate that recombinant human PFKFB4 kinase activity is 4.3-fold greater
than its phosphatase activity, siRNA and genomic deletion of PFKFB4 decrease
F2,6BP, PFKFB4 over-expression increases F2,6BP and selective PFKFB4 inhibition
in vivo markedly reduces F2,6BP, glucose uptake and ATP. Last, we find that
PFKFB4 is required for cancer cell survival during the metabolic response to
hypoxia, presumably to enable glycolytic production of ATP when the electron
transport chain is not fully operational. Taken together, our data indicate that
the PFKFB4 expressed in multiple transformed cells and tumors functions to
synthesize F2,6BP. We predict that pharmacological disruption of the PFKFB4
kinase domain may have clinical utility for the treatment of human cancers.
PMID- 25115399
TI - Nuclear and cytoplasmic p53 suppress cell invasion by inhibiting respiratory
complex-I activity via Bcl-2 family proteins.
AB - Although the p53 tumor suppressor/transcription factor often accumulates in the
cytoplasm of healthy cells, limited information is available on the cytoplasmic
function of p53. Here, we show that cytoplasmic p53 suppresses cell invasion by
reducing mitochondrial reactive oxygen species (ROS) levels. Analysis revealed
that this function is mediated by Bcl-2 family proteins: Cytoplasmic p53 binds
Bcl-w, liberating Bax, which then binds ND5, a subunit of respiratory complex-I,
thereby suppressing complex-I activity and thus ROS production. The G13289A
mutation of ND5, identified in cancer patients, prevents Bax/ND5 interactions and
promotes ROS production and cell invasion. We also showed that Bcl-XL and Bak can
substitute for Bcl-w and Bax, respectively, regulating complex-I activity and
supporting the cytoplasmic function of p53; nuclear p53 also suppresses complex-I
activity by inducing Bax expression. Studies in animal models support the notion
that p53 and Bcl-2 family proteins exhibit these functions in vivo. This study
demonstrates a link between p53 and Bcl-2 proteins as regulators of ROS
production and cellular invasiveness, and reveals complex-I, especially ND5, as
their functional target.
PMID- 25115401
TI - Concerted action of target-site mutations and high EPSPS activity in glyphosate
resistant junglerice (Echinochloa colona) from California.
AB - BACKGROUND: Echinochloa colona is an annual weed affecting field crops and
orchards in California. An E. colona population carrying a mutation in the EPSPS
gene endowing resistance to glyphosate, the most widely used non-selective
herbicide, was recently identified in the Northern Sacramento Valley of
California. Plants from this population, from a suspected glyphosate-resistant
(GR) population, and from one susceptible (S) population collected in the
Northern Sacramento Valley of California, were used to generate three GR and one
S selfed lines to study possible mechanisms involved in glyphosate resistance.
RESULTS: Based on the amount of glyphosate required to kill 50% of the plants
(LD50 ), GR lines were 4-9-fold more resistant than S plants and accumulated less
shikimate after glyphosate treatment. GR and S lines did not differ in glyphosate
absorption, translocation or metabolism. A different target-site mutation was
found in each of two of the GR lines corresponding to Pro106Thr and Pro106Ser
substitutions; the mutations were found in different homoeologous EPSPS genes. No
mutation was found in the third GR line, which exhibited 1.4-fold higher basal
EPSPS activity and a fivefold greater LD50 than S plants. Quantitative RT-PCR
revealed that GR lines had similar or lower EPSPS expression than S plants.
CONCLUSION: It is demonstrated that individuals with different glyphosate
resistance mechanisms can coexist in the same population, individuals from
different populations may carry different resistance mechanisms and different
mechanisms can act in concert within single E. colona plants. However, other
plant factors or resistance mechanisms appear to modulate plant expression of
EPSPS sensitivity to glyphosate.
PMID- 25115400
TI - Beclin-1-independent autophagy positively regulates internal ribosomal entry site
dependent translation of hypoxia-inducible factor 1alpha under nutrient
deprivation.
AB - Hypoxia has been shown to induce hypoxia-inducible factor-1alpha (HIF-1alpha)
expression to support many cellular changes required for tumor growth and
metastasis. In addition to hypoxia, nutrient deprivation is another stress
condition widely existing in solid tumors due to the poor blood supply. Our data
showed that nutrient deprivation induces a significant HIF-1alpha protein
expression and potentiates the HIF-1alpha responses of hypoxia and CoCl2. This
effect is not because of enhancement of HIF-1alpha stability or transcription.
Rather we found it is through the cap-independent but internal ribosome entry
site (IRES)-dependent translation. Notably inhibition of autophagy by si-ATG5, 3
methyladenine and chloroquine, but not si-Beclin-1, significantly reverses
nutrient deprivation-induced HIF-1alpha responses. Furthermore, it is interesting
to note the contribution of IRES activation for hypoxia-induced HIF-1alpha
expression, however, different from nutrient starvation, si-Beclin 1 but not si
ATG5 can inhibit hypoxia-induced HIF-1alpha IRES activation and protein
expression. Taken together, we for the first time highlight a link from
alternative autophagy to cap-independent protein translation of HIF-1alpha under
two unique stress conditions. We demonstrate Beclin 1-independent autophagy is
involved to positively regulate nutrient deprivation induced-HIF-1alpha IRES
activity and protein expression, while ATG5-independent autophagy is involved in
the HIF-1 IRES activation caused by hypoxia.
PMID- 25115404
TI - Annular lupus erythematosus profundus.
PMID- 25115402
TI - MicroRNAs differentially regulated in cardiac and skeletal muscle in health and
disease: potential drug targets?
AB - The identification of non-coding RNA species, previously thought of as 'junk'
DNA, adds a new dimension of complexity to the regulation of DNA, RNA and
protein. MicroRNAs are short non-coding RNA species that control gene expression,
are dysregulated in settings of cardiac and skeletal muscle disease and have
emerged as promising therapeutic targets. MicroRNAs specifically enriched in
cardiac and skeletal muscle are called myomiRs and play an important role in
cardiac pathology and skeletal muscle biology. Moreover, microRNA profiles are
altered in response to exercise and disease; thus, their potential as therapeutic
drug targets is being widely explored. In the cardiovascular field, therapeutic
inhibition of microRNAs has been shown to be effective in improving cardiac
outcome in preclinical cardiac disease models. MicroRNAs that promote skeletal
muscle regeneration are attractive therapeutic targets in muscle wasting
conditions where regenerative capacity is compromised.
PMID- 25115403
TI - Integrating team resource management program into staff training improves staff's
perception and patient safety in organ procurement and transplantation: the
experience in a university-affiliated medical center in Taiwan.
AB - BACKGROUND: The process involved in organ procurement and transplantation is very
complex that requires multidisciplinary coordination and teamwork. To prevent
error during the processes, teamwork education and training might play an
important role. We wished to evaluate the efficacy of implementing a Team
Resource Management (TRM) program on patient safety and the behaviors of the team
members involving in the process. METHODS: We implemented a TRM training program
for the organ procurement and transplantation team members of the National Taiwan
University Hospital (NTUH), a teaching medical center in Taiwan. This 15-month
intervention included TRM education and training courses for the healthcare
workers, focused group skill training for the procurement and transplantation
team members, video demonstration and training, and case reviews with feedbacks.
Teamwork culture was evaluated and all procurement and transplantation cases were
reviewed to evaluate the application of TRM skills during the actual processes.
RESULTS: During the intervention period, a total of 34 staff members participated
the program, and 67 cases of transplantations were performed. Teamwork framework
concept was the most prominent dimension that showed improvement from the
participants for training. The team members showed a variety of teamwork
behaviors during the process of procurement and transplantation during the
intervention period. Of note, there were two potential donors with a positive HIV
result, for which the procurement processed was timely and successfully
terminated by the team. None of the recipients was transplanted with an infected
organ. No error in communication or patient identification was noted during
review of the case records. CONCLUSION: Implementation of a Team Resource
Management program improves the teamwork culture as well as patient safety in
organ procurement and transplantation.
PMID- 25115405
TI - Quantitative analysis of intracellular communication and signaling errors in
signaling networks.
AB - BACKGROUND: Intracellular signaling networks transmit signals from the cell
membrane to the nucleus, via biochemical interactions. The goal is to regulate
some target molecules, to properly control the cell function. Regulation of the
target molecules occurs through the communication of several intermediate
molecules that convey specific signals originated from the cell membrane to the
specific target outputs. RESULTS: In this study we propose to model intracellular
signaling network as communication channels. We define the fundamental concepts
of transmission error and signaling capacity for intracellular signaling
networks, and devise proper methods for computing these parameters. The developed
systematic methodology quantitatively shows how the signals that ligands provide
upon binding can be lost in a pathological signaling network, due to the presence
of some dysfunctional molecules. We show the lost signals result in message
transmission error, i.e., incorrect regulation of target proteins at the network
output. Furthermore, we show how dysfunctional molecules affect the signaling
capacity of signaling networks and how the contributions of signaling molecules
to the signaling capacity and signaling errors can be computed. The proposed
approach can quantify the role of dysfunctional signaling molecules in the
development of the pathology. We present experimental data on caspese3 and T cell
signaling networks to demonstrate the biological relevance of the developed
method and its predictions. CONCLUSIONS: This study demonstrates how signal
transmission and distortion in pathological signaling networks can be modeled and
studied using the proposed methodology. The new methodology determines how much
the functionality of molecules in a network can affect the signal transmission
and regulation of the end molecules such as transcription factors. This can lead
to the identification of novel critical molecules in signal transduction
networks. Dysfunction of these critical molecules is likely to be associated with
some complex human disorders. Such critical molecules have the potential to serve
as proper targets for drug discovery.
PMID- 25115406
TI - A predisposition for allergies predicts subsequent hypertension, dyslipidemia,
and diabetes mellitus among patients with schizophrenia or bipolar disorder: a
nationwide longitudinal study.
AB - BACKGROUND: Previous studies have shown that both severe mental disorders
(schizophrenia and bipolar disorder) and atopic diseases were associated with an
increased risk of metabolic syndrome. However, the role of atopy/the
predisposition for allergies in the development of metabolic syndrome is still
unknown among those with severe mental disorders. METHODS: Using the Taiwan
National Health Insurance Research Database, 5826 patients with schizophrenia or
bipolar disorder (1908 with a predisposition for allergies and 3918 without) were
enrolled between 1998 and 2008. Those who developed hypertension, dyslipidemia,
and/or diabetes mellitus were identified during the follow-up to the end of 2011.
RESULTS: A predisposition for allergies increased the risk of developing
hypertension (HR: 1.67), dyslipidemia (HR: 1.82), and diabetes mellitus (HR:
1.37) in later life among those with severe mental disorders. A dose-dependent
relationship was noted between having more atopic comorbidities and a greater
likelihood of hypertension (1 atopic disease: HR: 1.60; ? 2 atopic comorbidities:
HR: 1.87), dyslipidemia (HR: 1.73; HR: 2.12), and diabetes mellitus (HR: 1.26;
HR: 1.69). CONCLUSION: A predisposition for allergies was an independent risk
factor for hypertension, dyslipidemia, and diabetes mellitus among patients with
schizophrenia or bipolar disorder. Further studies would be required to elucidate
the underlying pathophysiology among atopy, schizophrenia, bipolar disorder, and
metabolic syndrome.
PMID- 25115407
TI - Increased visual gamma power in schizoaffective bipolar disorder.
AB - BACKGROUND: Electroencephalography and magnetoencephalography (MEG) studies have
identified alterations in gamma-band (30-80 Hz) cortical activity in
schizophrenia and mood disorders, consistent with neural models of disturbed
glutamate (and GABA) neuron influence over cortical pyramidal cells. Genetic
evidence suggests specific deficits in GABA-A receptor function in
schizoaffective bipolar disorder (SABP), a clinical syndrome with features of
both bipolar disorder and schizophrenia. This study investigated gamma
oscillations in this under-researched disorder. METHOD: MEG was used to measure
induced gamma and evoked responses to a visual grating stimulus, known to be a
potent inducer of primary visual gamma oscillations, in 15 individuals with
remitted SABP, defined using Research Diagnostic Criteria, and 22 age- and sex
matched healthy controls. RESULTS: Individuals with SABP demonstrated increased
sustained visual cortical power in the gamma band (t 35 = -2.56, p = 0.015)
compared to controls. There were no group differences in baseline gamma power,
transient or sustained gamma frequency, alpha band responses or pattern onset
visual-evoked responses. CONCLUSIONS: Gamma power is increased in remitted SABP,
which reflects an abnormality in the cortical inhibitory-excitatory balance.
Although an interaction between gamma power and medication can not be ruled out,
there were no group differences in evoked responses or baseline measures. Further
work is needed in other clinical populations and at-risk relatives. Pharmaco
magnetoencephalography studies will help to elucidate the specific GABA and
glutamate pathways affected.
PMID- 25115408
TI - Pyonephrosis Caused by Salmonella Typhi: A Case Report.
AB - INTRODUCTION: Salmonella is a rare cause of urinary tract infections. We report
here a unique case of pyonephrosis due to Salmonella Typhi (S. Typhi)
complication, a stone-related obstructive pyelonephritis. CASE REPORT: A 47-year
old man, without any history of typhoid fever or gastrointestinal symptoms,
presented with a pyonephrosis and life-threatening bacteremia following an acute
obstructive right pyelonephritis caused by S. Typhi. The patient was treated by
urinary drainage (ureteral stent), antibiotics, and delayed right nephrectomy. We
postulated that urolithiasis could explain asymptomatic chronic urinary carriage
of S. Typhi. CONCLUSION: S. Typhi is one possible cause of life-threatening
urinary tract infection, especially in the context of urolithiasis.
PMID- 25115409
TI - Ethylene transposition: ruthenium hydride catalyzed intramolecular trans
silylvinylation of internal alkynes.
AB - A highly selective intramolecular trans-silylvinylation of internal alkynes
catalyzed by RuHCl(CO)(SIMes)(PPh3) has been accomplished. The use of methyl
vinyl ketone as an additive increased the efficiency of this transformation. This
process was used to successfully form five-, six-, and seven-membered
oxasilacycles by a formal anti-exo-dig cyclization.
PMID- 25115412
TI - The FIGO Leadership in Obstetrics and Gynecology for Impact and Change (LOGIC)
Initiative in Maternal and Newborn Health.
AB - The FIGO Leadership in Obstetrics and Gynecology for Impact and Change (LOGIC)
Initiative in Maternal and Newborn Health developed the organizational capacity
of national professional organizations of obstetrics and gynecology in eight
African and Asian countries. The initiative was funded by a grant from the Bill
and Melinda Gates Foundation and had three key objectives. These goals were to
support the eight FIGO member associations to strengthen their capacity to work
effectively; to influence national policies on maternal and newborn health; and
to work toward improving clinical practice in this area. The current supplement
presents evidence that the focus and effectiveness of a national obstetric and
gynecologic association-as well as its influence on major public health issues
(such as United Nations Millennium Development Goals 4 and 5)-can be
substantially broadened and enhanced by the provision of external support.
PMID- 25115411
TI - Associated morbidity of pediatric ptosis - a large, community based case-control
study.
AB - PURPOSE: To report the incidence, demographics, and associations of various
conditions among patients with pediatric ptosis. METHODS: A retrospective,
observational case-control study of patients (birth-18 years; n = 2,408)
diagnosed with pediatric ptosis in 1/2003-12/2012. Age- and gender-matched
control patients (n = 9,632) were randomly selected from the district members.
Medical and socio-demographic information were extracted from electronic medical
records. RESULTS: The average age of diagnosis was 5.6 years, and 1,325 (54%)
were male, with an incidence of 19.9/100,000. Systemic conditions significantly
associated with pediatric ptosis include myasthenia gravis, congenital anomalies,
deafness, mental retardation, muscular dystrophy, neurological diseases,
epilepsy, schizophrenia, and malignancy. Ophthalmic conditions associated with
pediatric ptosis include exotropia, progressive external ophthalmoplegia,
hypotropia, esotropia, hyperopia, vertical heterophoria, intermitent esotropia,
astigmatism, retinopathy, internuclear ophthalmoplegia, and myopia. Symptoms of
diplopia, blurred vision, and aniseikonia were significantly more common.
CONCLUSION: Pediatric ptosis is associated with various systemic and ophthalmic
conditions, and many are diagnosed after the age of 5 years. Clinicians should
maintain a high degree of suspicion and thoroughly evaluate all patients with
pediatric ptosis to properly assess underlying systemic associations. A better
understanding of the patho-physiological association between these factors and
pediatric ptosis may help its prevention and treatment.
PMID- 25115413
TI - Revising the high-density lipoprotein targeting strategies - insights from human
and preclinical studies.
AB - In recent years, the high-density lipoprotein (HDL) hypothesis has been
challenged. Several completed randomized clinical trials continue to fall short
in demonstrating HDL, or at least HDL-cholesterol (HDL-C) levels, as being a
consistent target in the prevention of cardiovascular diseases. However,
population studies and findings in lipid modifying trials continue to strongly
support HDL-C as a superb risk predictor. It is increasingly evident that the
complexity of HDL metabolism confounds the use of HDL-C concentration as a
unified target. However, important insights continue to emerge from the post hoc
analyses of recently completed (i) fibrate-based FIELD and ACCORD trials,
including the unexpected beneficial effect of fibrates in microvascular diseases,
(ii) the niacin-based AIM-HIGH and HPS2-THRIVE studies, (iii) recombinant HDL
based as well as (iv) the completed CETP inhibitor-based trials. These together
with on-going mechanistic studies on novel pathways, which include the unique
roles of microRNAs, post-translational remodeling of HDL and novel pathways
related to HDL modulators will provide valuable insights to guide how best to
refocus and redesign the conceptual framework for selecting HDL-based targets.
PMID- 25115414
TI - Proton magnetic resonance spectroscopy assessment of fetal brain metabolism in
late-onset 'small for gestational age' versus 'intrauterine growth restriction'
fetuses.
AB - OBJECTIVES: We used magnetic resonance spectroscopy (MRS) to evaluate brain
metabolic differences in small fetuses near term as compared to appropriate for
gestational age (AGA) fetuses. STUDY DESIGN: 71 term small fetuses (estimated
fetal weight <10th centile for gestational age with normal umbilical artery
Doppler sonography) were subclassified as late intrauterine growth restriction
(IUGR) (n = 50) or small for gestational age (SGA) (n = 21), and compared with 65
AGA fetuses. IUGR was defined by either abnormal middle cerebral artery, abnormal
uterine artery Doppler sonography or estimated fetal weight <3rd centile. All
participants underwent brain magnetic resonance imaging at 37 weeks of gestation,
and single-voxel magnetic resonance spectra were obtained from the frontal lobe
on a 3-tesla scanner. N-acetylaspartate (NAA)/choline (Cho), NAA/creatine (Cr)
and Cho/Cr ratios were calculated and compared between cases and controls. The
association of the metabolic ratios with the study groups was tested. RESULTS:
After MRS processing and applying quality control criteria, 31 spectra from late
onset IUGR, 11 from SGA and 30 from AGA fetuses were selected for further
analysis. Both SGA and late-onset IUGR fetuses showed significantly reduced
NAA/Cho levels when compared to AGA fetuses. This decrease followed a linear
trend across the three clinical groups that were considered. CONCLUSIONS: Both
SGA and late-onset IUGR fetuses showed differences in MRS brain metabolic ratios.
The findings suggest that despite near-normal perinatal outcomes, SGA fetuses are
not constitutionally small and may represent a form of growth disorder that needs
to be clarified.
PMID- 25115415
TI - Memories of Holocaust-related traumatic experiences, sense of coherence, and
survivors' subjective well-being in late life: some puzzling findings.
AB - BACKGROUND AND OBJECTIVES: This study explores the nexus of relationships between
memories of Holocaust-related early traumatic events, survivors' sense of
coherence (SOC), and subjective well-being (SWB) in late life. DESIGN: The basic
design of this study, based 106 survivors (54% female), was cross-sectional.
METHODS: Participants underwent an extensive in-depth clinical interview relating
to their Holocaust experiences and responded to measures of SOC and SWB. RESULTS:
These data provided no evidence for the moderating or "buffering" effect of SOC
but showed support for indirect effects of SOC in the relationship between memory
traces of specific traumatic experiences and adaptive outcomes. CONCLUSIONS: The
results of the present study provide support for Antonovsky's salutogenic
perspective. It is highly plausible that survivors who underwent severe
experiences during the Holocaust period were forced to call upon all their inner
strengths and coping resources,and that their success in doing so and also
surviving this horrendous period, might have contributed to the development of a
stronger sense of meaning and coherence, which, in turn lead to a better sense of
mental health as they approach the final season of their lives.
PMID- 25115410
TI - Temporal trends from 1986 to 2008 in overall survival of small cell lung cancer
patients.
AB - OBJECTIVES: An assessment of temporal trends in patient survival is important to
determine the progress toward patient outcomes and to reveal where advancements
must be made. This study assessed temporal changes spanning 22years in
demographics, clinical characteristics, and overall survival of small cell lung
cancer (SCLC) patients. MATERIALS AND METHODS: This analysis included 1032 SCLC
patients spanning two time-periods from the H. Lee Moffitt Cancer Center and
Research Institute: 1986-1999 (N=410) and 2000-2008 (N=622). Kaplan-Meier
survival curves and log-rank statistics were used to assess survival rates across
the two time-periods and multivariable Cox proportional hazards models were used
to generate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The
overall 5-year survival rate significantly increased from 8.3% for the 1986-1999
time-period to 11.0% (P<0.001) for the 2000-2008 time-period, and the median
survival time increased from 11.3months (95% CI 10.5-12.7) to 15.2months (95% CI
13.6-16.6). We also observed significant increases in stage-specific median
survival times and survival rates across the two time-periods. A multivariable
Cox proportional hazards model for the entire cohort revealed significant
increased risk of death for patients diagnosed in 1986-1999 (HR=1.29; 95% CI 1.11
1.49), patients diagnosed between 60 and 69years of age (HR=1.33; 95% CI 1.04
1.49) and over 70years of age (HR=1.63; 95% CI 1.26-2.11), men (HR=1.33; 95% CI
1.16-1.53), patients with no first course treatment (HR=2.17; 95% CI 1.57-3.00)
and extensive stage SCLC (HR=2.79; 95% CI 2.35-3.30). CONCLUSION: This analysis
demonstrated significant improvements in overall and stage-specific median
survival times and survival rates of SCLC patients treated at the Moffitt Cancer
Center from 1986 to 2008.
PMID- 25115416
TI - Effect of hyoscine N-butylbromide on adenoma detection rate: meta-analysis of
randomized clinical trials.
AB - BACKGROUND AND AIM: Anti-spasmodic drugs may facilitate mucosal inspection during
colonoscopy. The impact of hyoscine N-butylbromide (HBB) on polyp detection rate
(PDR) and adenoma detection rate (ADR) is unclear. METHODS: We conducted a
reproducible literature search of multiple databases. Two reviewers independently
compared manuscripts for PDR, ADR, advanced adenoma detection rate (AADR), and
rates of complications. Pooling was conducted by fixed-effects and random-effects
models. Relative risk (RR) estimates were calculated (95% confidence interval).
I(2) index assessed heterogeneity. RESULTS: Patient demographics were comparable.
The pooled analysis showed a trend toward improving PDR and ADR among the HBB
group compared with the placebo group but failed to reach statistical
significance, (46% vs 43%, RR = 1.08 [0.94, 1.25], P = 0.27), (31% vs 28%, RR =
1.12 [0.97, 1.29], P = 0.11) respectively. CONCLUSION: HBB during colonoscopy may
provide marginal improvements in ADR and PDR. However, heterogeneity in the
available data precludes firm conclusions at this time.
PMID- 25115417
TI - Lessons learned from the study of 10,000 patients with soft tissue sarcoma.
AB - BACKGROUND AND OBJECTIVE: The management of rare tumors is difficult because of
limited information on natural history. Our objective was to describe a long-term
comprehensive prospective database with the assumption that with careful
attention to patient, predisposing tumor and treatment variables, valuable
knowledge could be obtained that could guide management. METHODS: In July of
1982, we began a prospective database of all adult patients admitted to our
institution for a surgical procedure for soft tissue sarcoma. Patients were
included if they had primary, locally recurrent or metastatic disease undergoing
a surgical procedure. RESULTS: Over 3 decades, we entered 10,000 patients into
our prospective soft tissue sarcoma database. Data were entered on a weekly or
biweekly schedule with full participation of a multidisciplinary team and a
dedicated sarcoma pathologist. Extensive information is available from this
database. In this article, we describe distribution by site, histopathology, sex,
size, and grade. We utilize this information along with outcome data for local
recurrence, distant recurrence, disease specific, and overall survival. The value
of molecular diagnosis is illustrated. CONCLUSIONS: Continuous prospective long
term databases are important to obtain knowledge particularly for rare tumors.
Such data can be a rich resource for the development of prognostic indicators
including nomograms and can be analyzed by Bayesian Belief Networks. These long
term data linked to collection of tumor and germ-line tissue at the time of an
initial procedure will remain a resource for future decades.
PMID- 25115418
TI - Risk of readmission and emergency surgery following nonoperative management of
colonic diverticulitis: a population-based analysis.
AB - OBJECTIVE: To characterize the clinical course of patients with diverticulitis
after nonoperative management and determine factors associated with readmission
and subsequent emergency surgery. BACKGROUND: Clinical course of this disease
remains poorly understood; indications for elective colectomy are unclear.
METHODS: This was a retrospective cohort study of patients managed nonoperatively
after a first episode of diverticulitis in Ontario, Canada (2002-2012). Time-to
event analysis and Fine and Gray multivariable regression were used to
characterize the risks of readmission and emergency surgery for diverticulitis,
accounting for death and elective colectomy as competing events. RESULTS: A total
of 14,124 patients were followed for a median of 3.9 years (maximum 10,
interquartile range: 1.7-6.4). Five-year cumulative incidence was 9.0% for
readmission, 1.9% for emergency surgery, and 14.1% for all-cause mortality.
Patients younger than 50 years had higher incidence of readmission than patients
aged 50 years and older (10.5% vs 8.4%; P < 0.001) but not emergency surgery
(1.8% vs 2.0%; P = 0.52). Patients with complicated disease (abscess,
perforation) were at increased risk of readmission than those with uncomplicated
disease (12.0% vs 8.2%; P < 0.001), as well as increased risk of emergency
surgery (4.3% vs 1.4%, P < 0.001). In multivariable regression, complicated
disease and number of prior admissions were associated with increased risk of
emergency surgery, yet age less than 50 years was not. Risks associated with
complicated disease were nonproportional over time, being highest immediately
after discharge and decreasing thereafter. CONCLUSIONS: Absolute risks of
readmission and emergency surgery are low after nonoperative management of
diverticulitis, providing evidence for the practice of deferring colectomy for
patients without persistent symptoms or multiple recurrences.
PMID- 25115420
TI - The HYSLAR trial: a prospective randomized controlled trial of the use of a
restrictive fluid regimen with 3% hypertonic saline versus lactated Ringers in
patients undergoing pancreaticoduodenectomy.
AB - OBJECTIVE: This study was designed to determine whether the volume and type of
fluid administered for pancreaticoduodenectomy impacts postoperative outcomes.
BACKGROUND: Three percent hypertonic saline (HYS) has been suggested as a means
of reducing the volume of fluid required to sustain tissue perfusion in the
perioperative period. METHODS: Between May 2011 and November 2013, patients
undergoing pancreaticoduodenectomy were enrolled in an institutional review board
approved, single-center, prospective, parallel, randomized controlled trial (NCT
01428050), comparing lactated Ringers (LAR) (15 mL/kg/hr LAR intraoperation, 2
mL/kg/hr LAR postoperation) with HYS (9 mL/kg/hr LAR and 1 mL/kg/hr HYS
intraoperation, 1 mL/kg/hr HYS postoperation). RESULTS: A total of 264 patients
were randomized. Demographic variables between groups were similar. The HYS
patients had a significantly reduced net fluid balance (65 vs 91 mL/kg, P =
0.02). The overall complication rate was reduced in the HYS group (43% vs 54%),
with a relative risk of 0.79 [95% confidence interval (CI), 0.62-1.02; P =
0.073], factoring stratification for pancreas texture. After adjustment for age
and weight, the relative risk was 0.75 [95% CI (0.58-0.96); P = 0.023]. The total
number of complications was significantly reduced in the HYS group (93 vs 123),
with an incidence rate ratio of 0.74 [95% CI (0.56-0.97); P = 0.027]. After
adjustment for age and weight, the incidence rate ratio was 0.69 [95% CI (0.52
0.90); P = 0.0068]. Reoperations, length of stay, readmissions, and 90-day
mortality were similar between groups. CONCLUSIONS: A moderately restrictive
fluid regimen with HYS resulted in a statistically significant 25% reduction in
complications when adjusted for age, weight, and pancreatic texture.
PMID- 25115419
TI - The enteric nervous system neuropeptide, bombesin, reverses innate immune
impairments during parenteral nutrition.
AB - BACKGROUND: Lack of enteral stimulation during parenteral nutrition (PN) impairs
mucosal immunity. Bombesin (BBS), a gastrin-releasing peptide analogue, reverses
PN-induced defects in acquired immunity. Paneth cells produce antimicrobial
peptides (AMPs) of innate immunity for release after cholinergic stimulation.
OBJECTIVE: Determine if BBS restores AMPs and bactericidal function during PN.
METHODS: Intravenously cannulated male ICR mice were randomized to Chow, PN, or
PN+BBS (15 MUg 3 times daily, n = 7 per group) for 5 days. Ileum was analyzed for
AMPs (Protein: sPLA2 by fluorescence, lysozyme and RegIII-gamma by western
andcryptdin-4 by ELISA; mRNA: all by RT-PCR). Cholinergic stimulated (100 MUM
bethanechol) ileal specimens assessed Pseudomonas bactericidal activity. Ileum
(Chow: n = 7; PN: n = 9; PN+BBS: n = 8) was assessed for Escherichia coli
invasion in ex-vivo culture. RESULTS: PN significantly decreased most AMPs versus
Chow while BBS maintained Chow levels (sPLA2: Chow: 107 + 14*, PN: 44.6 + 7.2,
PN+BBS: 78.7 + 13.4* Fl/min/MUL/total protein; Lysozyme: Chow: 63.9 + 11.9*, PN:
26.8 + 6.2; PN+BBS: 64.9 + 13.8* lysozyme/total protein; RegIII-gamma: Chow: 51.5
+ 10.0*, PN: 20.4 + 4.3, PN+BBS: 31.0 + 8.4 RegIII-gamma/total protein; Cryptdin
4: Chow: 18.4 + 1.5*, PN: 12.7 + 1.6, PN+BBS: 26.1 + 2.4*? pg/mg [all *P < 0.05
vs PN and ?P < 0.05 vs Chow]). Functionally, BBS prevented PN loss of
bactericidal activity after cholinergic stimulation (Chow: 25.3 + 3.6*, PN: 13.0
+ 3.2; PN+BBS: 27.0 + 4.7* percent bacterial killing, *P < 0.05 vs PN). BBS
reduced bacterial invasion in unstimulated tissue barely missing significance (P
= 0.06). CONCLUSIONS: The enteric nervous system (ENS) controls AMP levels in
Paneth cells during PN but mucosal protection by innate immunity requires both
ENS and parasympathetic stimulation.
PMID- 25115422
TI - Disease severity, not operative approach, drives organ space infection after
pediatric appendectomy.
AB - OBJECTIVE: This study examines patient and operative factors associated with
organ space infection (OSI) in children after appendectomy, specifically focusing
on the role of operative approach. BACKGROUND: Although controversy exists
regarding the risk of increased postoperative intra-abdominal infections after
laparoscopic appendectomy, this approach has been largely adopted in the
treatment of pediatric acute appendicitis. METHODS: Children aged 2 to 18 years
undergoing open or laparoscopic appendectomy for acute appendicitis were selected
from the 2012 American College of Surgeons Pediatric National Surgical Quality
Improvement Program database. Univariate analysis compared patient and operative
characteristics with 30-day OSI and incisional complication rates. Factors with a
P value of less than 0.1 and clinical importance were included in the
multivariable logistic regression models. A P value less than 0.05 was considered
significant. RESULTS: For 5097 children undergoing appendectomy, 4514 surgical
procedures (88.6%) were performed laparoscopically. OSI occurred in 155 children
(3%), with half of these infections developing postdischarge. Significant
predictors for OSI included complicated appendicitis, preoperative sepsis, wound
class III/IV, and longer operative time. Although 5.2% of patients undergoing
open surgery developed OSI (odds ratio = 1.82; 95% confidence interval, 1.21
2.76; P = 0.004), operative approach was not associated with increased relative
odds of OSI (odds ratio = 0.99; confidence interval, 0.64-1.55; P = 0.970) after
adjustment for other risk factors. Overall, the model had excellent predictive
ability (c-statistic = 0.837). CONCLUSIONS: This model suggests that disease
severity, not operative approach, as previously suggested, drives OSI development
in children. Although 88% of appendectomies in this population were performed
laparoscopically, these findings support utilization of the surgeon's preferred
surgical technique and may help guide postoperative counsel in high-risk
children.
PMID- 25115423
TI - Primary hyperparathyroidism with negative imaging: a significant clinical
problem.
AB - OBJECTIVE: To compare the outcomes for patients undergoing parathyroidectomy for
primary hyperparathyroidism by imaging results. BACKGROUND: Preoperative imaging
plays an increasingly important role in the evaluation of primary
hyperparathyroidism, and surgical referral may be predicated upon successful
imaging. METHODS: We performed a retrospective study of patients undergoing
initial parathyroidectomy for primary hyperparathyroidism (2002-2014). Patients
were classified as nonlocalized when preoperative imaging failed to identify
affected gland(s) and localized if successful. Primary outcome was cure, defined
as eucalcemia postoperatively. Intraoperative success, defined by intraoperative
parathyroid hormone criteria, and complication rates were also analyzed.
Localized and nonlocalized patients were matched (1:1) utilizing a propensity
score. Logistic regression determined factors associated with localization in the
matched cohort. RESULTS: Of 2185 patients, 38.3% (n = 836) were nonlocalized.
Nonlocalized patients had smaller parathyroids by size (1.2 vs 1.6 cm, P < 0.001)
and mass (250 vs 537 mg, P < 0.001), higher incidence of hyperplasia (12.8% vs
5.4%, P < 0.001) and lower incidence of single adenoma (73.6 vs 86.0%, P < 0.001)
compared with localized patients. There was no difference in intraoperative
success (93.9 vs 95.6%, P = 0.073) or cure rates (96.2% vs 97.7%, P = 0.291)
between nonlocalized and localized groups. In a propensity-matched cohort of 452
patients, there was no significant difference in cure rates (97.8 vs 97.4%, P =
0.760) between nonlocalized patients and matched localized controls. CONCLUSIONS:
Nonlocalization of abnormal glands preoperatively is not associated with a
decreased surgical cure rate for primary hyperparathyroidism. Referral for
surgical evaluation should be based on biochemical diagnosis rather than
localization by imaging.
PMID- 25115421
TI - Increased trauma center volume is associated with improved survival after severe
injury: results of a Resuscitation Outcomes Consortium study.
AB - OBJECTIVE: To investigate the relationship between trauma center volume and
outcome. BACKGROUND: The Resuscitation Outcomes Consortium is a network of 11
centers and 60 hospitals conducting emergency care research. For many procedures,
high-volume centers demonstrate superior outcomes versus low-volume centers. This
remains controversial for trauma center outcomes. METHODS: This study was a
secondary analysis of prospectively collected data from the Resuscitation
Outcomes Consortium multicenter out-of-hospital Hypertonic Saline Trial in
patients with Glasgow Coma Scale score of 8 or less (traumatic brain injury) or
systolic blood pressure of 90 or less and pulse of 110 or more (shock).
Regression analyses evaluated associations between trauma volume and the
following outcomes: 24-hour mortality, 28-day mortality, ventilator-free days,
Multiple Organ Dysfunction Scale incidence, worst Multiple Organ Dysfunction
Scale score, and poor 6-month Glasgow Outcome Scale-Extended score. RESULTS: A
total of 2070 patients were evaluated: 1251 in the traumatic brain injury cohort
and 819 in the shock cohort. Overall, 24-hour and 28-day mortality was 16% and
25%, respectively. For every increase of 500 trauma center admissions, there was
a 7% decreased odds of 24-hour and 28-day mortality for all patients. As trauma
center volume increased, nonorgan dysfunction complications increased, ventilator
free days increased, and worst Multiple Organ Dysfunction Scale score decreased.
The associations with higher trauma center volume were similar for the traumatic
brain injury cohort, including better neurologic outcomes at 6 months, but not
for the shock cohort. CONCLUSIONS: Increased trauma center volume was associated
with increased survival, more ventilator-free days, and less severe organ
failure. Trauma system planning and implementation should avoid unnecessary
duplication of services.
PMID- 25115424
TI - Trainee participation is associated with adverse outcomes in emergency general
surgery: an analysis of the National Surgical Quality Improvement Program
database.
AB - OBJECTIVE: To identify whether resident involvement affects clinically relevant
outcomes in emergency general surgery. BACKGROUND: Previous research has
demonstrated a significant impact of trainee participation on outcomes in a broad
surgical patient population. METHODS: We identified 141,010 patients who
underwent emergency general surgery procedures in the 2005-2010 Surgeons National
Surgical Quality Improvement Program database. Because of the nonrandom
assignment of complex cases to resident participation, patients were matched
(1:1) on known risk factors [age, sex, inpatient status, preexisting
comorbidities (obesity, diabetes, smoking, alcohol, steroid use, coronary artery
disease, chronic renal failure, pulmonary disease)] and preoperatively calculated
probability for morbidity and mortality. Clinically relevant outcomes were
compared with a t or chi test. The impact of resident participation on outcomes
was assessed with multivariable regression modeling, adjusting for risk factors
and operative time. RESULTS: The most common procedures in the matched cohort (n
= 83,790) were appendectomy (39.9%), exploratory laparotomy (8.8%), and
adhesiolysis (6.6%). Trainee participation is independently associated with intra
and postoperative events, wound, pulmonary, and venous thromboembolic
complications, and urinary tract infections. CONCLUSIONS: Trainee participation
is associated with adverse outcomes in emergency general surgery procedures.
PMID- 25115426
TI - Does hospital accreditation impact bariatric surgery safety?
AB - OBJECTIVE: To evaluate the impact of hospital accreditation upon bariatric
surgery outcomes. BACKGROUND: Since 2004, the American College of Surgeons and
the American Society of Metabolic and Bariatric Surgery have accredited bariatric
hospitals. Few studies have evaluated the impact of hospital accreditation on all
bariatric surgery outcomes. METHODS: Bariatric surgery hospitalizations were
identified using International Classification of Diseases, Ninth Revision (ICD9)
codes in the 2010 Nationwide Inpatient Sample (NIS). Hospital names and American
Hospital Association (AHA) codes were used to identify accredited bariatric
centers. Relevant ICD9 codes were used for identifying demographics, length of
stay (LOS), total charges, mortality, complications, and failure to rescue (FTR)
events. RESULTS: There were 117,478 weighted bariatric patient discharges
corresponding to 235 unique hospitals in the 2010 NIS data set. A total of 72,615
(61.8%) weighted discharges, corresponding to 145 (61.7%) named or AHA
identifiable hospitals were included. Among the 145 hospitals, 66 (45.5%) were
unaccredited and 79 (54.5%) accredited. Compared with accredited centers,
unaccredited centers had a higher mean LOS (2.25 vs 1.99 days, P < 0.0001), as
well as total charges ($51,189 vs $42,212, P < 0.0001). Incidence of any
complication was higher at unaccredited centers than at accredited centers (12.3%
vs 11.3%, P = 0.001), as was mortality (0.13% vs 0.07%, P = 0.019) and FTR (0.97%
vs 0.55%, P = 0.046). Multivariable logistic regression analysis identified
unaccredited status as a positive predictor of incidence of complication [odds
ratio (OR) = 1.08, P < 0.0001], as well as mortality (OR = 2.13, P = 0.013).
CONCLUSIONS AND RELEVANCE: Hospital accreditation status is associated with safer
outcomes, shorter LOS, and lower total charges after bariatric surgery.
PMID- 25115425
TI - Value of intraoperative neck margin analysis during Whipple for pancreatic
adenocarcinoma: a multicenter analysis of 1399 patients.
AB - INTRODUCTION: During pancreaticoduodenectomy (PD) for ductal adenocarcinoma, a
frozen section (FS) neck margin is typically assessed, and if positive,
additional pancreas is removed to achieve an R0 margin. We analyzed the
association of this practice with improved overall survival (OS). METHODS:
Patients who underwent PD for pancreatic ductal adenocarcinoma from January 2000
to August 2012 at 8 academic centers were classified by neck margin status as
negative (R0) or microscopically positive (R1) on the basis of FS and permanent
section (PS). Impact on OS of converting an FS-R1-neck margin to a PS-R0-neck
margin by additional resection was assessed. RESULTS: A total of 1399 patients
had FS neck margins analyzed. Median OS was 19.7 months. On FS, 152 patients
(10.9%) were R1, and an additional 51 patients (3.6%) had false-negative FS-R0
margins. PS-R0-neck was achieved in 1196 patients (85.5%), 131 patients (9.3%)
remained PS-R1, and 72 patients (5.1%) were converted from FS-R1-to-PS-R0 by
additional resection. Median OS for PS-R0-neck patients was 21.1 months versus
13.7 months for PS-R1-neck patients (P < 0.001) and 11.9 months for FS-R1-to-PS
R0 patients (P < 0.001). Both FS-R1-to-PS-R0 and PS-R1-neck patients had larger
tumors (P = 0.001), more perineural invasion (P = 0.02), and more node positivity
(P = 0.08) than PS-R0-neck patients. On multivariate analysis controlling for
adverse pathologic factors, FS-R1-to-PS-R0 conversion remained associated with
significantly worse OS compared with PS-R0-neck patients (hazard ratio: 1.55; P =
0.009). CONCLUSIONS: For patients who undergo pancreaticoduodenectomy for
pancreatic ductal adenocarcinoma, additional resection to achieve a negative neck
margin after positive frozen section is not associated with improved OS.
PMID- 25115427
TI - Repair of extensive aortic aneurysms: a single-center experience using the
elephant trunk technique over 20 years.
AB - OBJECTIVES: We report the early and late outcomes after repair of extensive
aortic aneurysms using the 2-stage elephant trunk (ET) technique. BACKGROUND:
Management of aneurysm involving the entire aorta is a significant challenge.
Given the anatomical complexity, the staged ET procedure was devised. A paucity
of long-term data of outcomes of this approach exists. METHODS: A single-center
retrospective analysis of a prospectively collected database of all patients
undergoing repair for extensive aortic aneurysm was performed. RESULTS: Between
1991 and 2013, we repaired 3012 aneurysms of the ascending or thoracoabdominal
aorta. Of these, we performed 503 operations in 348 patients using the ET
technique. Mean age was 62.4 +/- 14.3 years, and 156/346 (45.1%) operations were
in women; 288 patients underwent first-stage ET with 157 receiving a complete
second-stage repair. Index repair early mortality was 29/317 (9.1%). Completion
stage early mortality was 17/186 = 9.1%. Stroke after first-stage ET repair was
10/297 (3.4%) and immediate neurologic deficit after the second-stage ET repair
was 6/206 (2.9%). In the 131 patients who did not receive a second-stage repair,
17.8% died in the interval between 31 and 45 days. CONCLUSIONS: Extensive aortic
aneurysm is a complex problem, but it can be managed safely with a 2-stage open
procedure. Those patients who could not complete the completion repair fared
poorly. Better predictors for early outcome need to be determined. The use of ET
technique remains a valuable approach for repair of extensive aortic aneurysm.
PMID- 25115428
TI - Laser resurfacing and remodeling of hypertrophic burn scars: the results of a
large, prospective, before-after cohort study, with long-term follow-up.
AB - OBJECTIVES: Hypertrophic burn scars produce significant morbidity, including
itching, pain, stiffness, and contracture, but best management practices remain
unclear. We present the largest study to date that examines long-term impact of
laser therapies, a potentially transformative technology, on scar remodeling.
METHODS: We conducted a prospective, before-after cohort study in burn patients
with hypertrophic scars. Pulsed-dye laser was used for pruritus and erythema;
fractional CO2 laser was used for stiffness and abnormal texture. Outcomes
included (1) Vancouver Scar Scale (VSS), which documents pigmentation, erythema,
pliability, and height, and (2) University of North Carolina "4P" Scar Scale
(UNC4P), which rates pain, pruritus, paresthesias, and pliability. RESULTS: A
total of 147 burn patients (mean age, 26.9 years; total body surface area, 16.1%)
received 415 laser sessions (2.8 sessions/patient), 16 months (median) after
injury, including pulsed dye laser (n = 327) and CO2 (n = 139). Laser treatments
produced rapid, significant, and lasting improvements in hypertrophic scar.
Provider-rated VSS dropped from 10.43 [standard deviation (SD) 2.37] to 5.16 (SD
1.92), by the end of treatments, and subsequently decreased to 3.29 (SD 1.24), at
a follow-up of 25 months. Patient-reported UNC4P fell from 5.40 (SD 2.54) to 2.05
(SD 1.67), after the first year, and further decreased to 1.74 (SD 1.72), by the
end of the study period. CONCLUSIONS: For the first time, ever, in a large
prospective study, laser therapies have been shown to dramatically improve both
the signs and symptoms of hypertrophic burn scars, as measured by objective and
subjective instruments. Laser treatment of burn scars represents a disruptive
innovation that can yield results not previously possible and may displace
traditional methods of operative intervention.
PMID- 25115429
TI - Addressing the appropriateness of elective colon resection for diverticulitis: a
report from the SCOAP CERTAIN collaborative.
AB - OBJECTIVE: To assess the reported indications for elective colon resection for
diverticulitis and concordance with professional guidelines. BACKGROUND: Despite
modern professional guidelines recommending delay in elective colon resection
beyond 2 episodes of uncomplicated diverticulitis, the incidence of elective
colectomy has increased dramatically in the last 2 decades. Whether surgeons have
changed their threshold for recommending a surgical intervention is unknown. In
2010, Washington State's Surgical Care and Outcomes Assessment Program initiated
a benchmarking and education initiative related to the indications for colon
resection. METHODS: Prospective cohort study evaluating indications from chronic
complications (fistula, stricture, bleeding) or the number of previously treated
diverticulitis episodes for patients undergoing elective colectomy at 1 of 49
participating hospitals (2010-2013). RESULTS: Among 2724 patients (58.7 +/- 13
years; 46% men), 29.4% had a chronic complication indication (15.6% fistula, 7.4%
stricture, 3.0% bleeding, 5.8% other). For the 70.5% with an episode-based
indication, 39.4% had 2 or fewer episodes, 56.5% had 3 to 10 episodes, and 4.1%
had more than 10 episodes. Thirty-one percent of patients failed to meet
indications for either a chronic complication or 3 or more episodes. Over the 4
years, the proportion of patients with an indication of 3 or more episodes
increased from 36.6% to 52.7% (P < 0.001) whereas the proportion of those who
failed to meet either clinical or episode-based indications decreased from 38.4%
to 26.4% (P < 0.001). The annual rate of emergency resections did not increase
significantly, varying from 5.6 to 5.9 per year (P = 0.81). CONCLUSIONS:
Adherence to a guideline based on 3 or more episodes for elective colectomy
increased concurrently with a benchmarking and peer-to-peer messaging initiative.
Improving adherence to professional guidelines related to appropriate care is
critical and can be facilitated by quality improvement collaboratives.
PMID- 25115430
TI - Preoperative methylprednisolone enhances recovery after endovascular aortic
repair: a randomized, double-blind, placebo-controlled clinical trial.
AB - OBJECTIVE: To evaluate effects of preoperative high-dose glucocorticoid on the
inflammatory response and recovery after endovascular aortic aneurysm repair
(EVAR). BACKGROUND: The postimplantation syndrome after EVAR may delay recovery
due to the release of proinflammatory mediators. Glucocorticoids may reduce
postoperative inflammatory responses and enhance recovery, but with limited
information on EVAR. METHODS: A single-center, randomized, double-blind, placebo
controlled trial of 153 patients undergoing elective EVAR between November 2009
and January 2013. Patients received 30 mg/kg of methylprednisolone (MP) (n = 77)
or placebo (n = 76) preoperatively. Primary outcome was a modified version of the
systemic inflammatory response syndrome. Secondary outcome measures were the
effect on inflammatory biomarkers, morbidity, and time to meet discharge
criteria. RESULTS: Of 153 randomized patients, 150 (98%) were evaluated for the
primary outcome. MP reduced systemic inflammatory response syndrome from 92% to
27% (P < 0.0001) (number needed to treat = 1.5), maximal plasma interleukin 6
from 186 pg/mL [interquartile range (IQR) = 113-261 pg/mL] to 20 pg/mL (IQR = 11
28 pg/mL) (P < 0.001) and fulfillment of discharge criteria was shorter [2 days
(IQR = 2-4 days) vs 3 days (IQR = 3-4 days)] (P < 0.001). C-reactive protein,
temperature, interleukin 8, and soluble tumor necrosis factor receptor were also
reduced (P < 0.001) by MP. Myeloperoxidase, D-dimer, and matrix metalloproteinase
9 were not modified. No differences in 30-day medical (23% vs 36%) (P = 0.1) or
surgical (20% vs 21%) morbidity were found in the active group versus the placebo
group. CONCLUSIONS: Preoperative MP attenuates the inflammatory response with a
faster recovery after EVAR for abdominal aortic aneurysms. Further safety and
dose-response studies are required to allow recommendations for general practice.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00989729.
PMID- 25115431
TI - Market competition influences renal transplantation risk and outcomes.
AB - OBJECTIVE: To evaluate the impact of market competition on patient mortality and
graft failure after kidney transplantation. BACKGROUND: Kidneys are initially
allocated within 58 donation service areas (DSAs), which have varying numbers of
transplant centers. Market competition is generally considered beneficial.
METHODS: The Scientific Registry of Transplant Recipients database was queried
and the Herfindahl-Hirschman index (HHI), a measure of market competition, was
calculated for each DSA from 2003 to 2012. Receipt of low-quality kidneys (Kidney
Donor Profile Index >= 85) was modeled with multivariable logistic regression,
and Cox proportional hazards models were created for graft failure and patient
mortality. RESULTS: A total of 127,355 adult renal transplants were performed.
DSAs were categorized as 7 no (HHI = 1), 17 low (HHI = 0.52-0.97), 17 medium (HHI
= 0.33-0.51), or 17 high (HHI = 0.09-0.32) competition. For deceased donor kidney
transplantation, increasing market competition was significantly associated with
mortality [hazard ratio (HR): 1.11, P = 0.01], graft failure (HR: 1.18, P =
0.0001), and greater use of low-quality kidneys (odds ratio = 1.39, P < 0.0001).
This was not true for living donor kidney transplantation (mortality HR: 0.94, P
= 0.48; graft failure HR: 0.99, P = 0.89). Competition was associated with longer
waitlists (P = 0.04) but not with the number of transplants per capita in a DSA
(P = 0.21). CONCLUSIONS: Increasing market competition is associated with
increased patient mortality and graft failure and the use of riskier kidneys.
These results may represent more aggressive transplantation and tolerance of
greater risk for patients who otherwise have poor alternatives. Market
competition should be better studied to ensure optimal outcomes.
PMID- 25115432
TI - Association between hospital imaging use and venous thromboembolism events rates
based on clinical data.
AB - OBJECTIVE: The objective was to assess the presence and extent of venous
thromboembolic (VTE) surveillance bias using high-quality clinical data.
BACKGROUND: Hospital VTE rates are publicly reported and used in pay-for
performance programs. Prior work suggested surveillance bias: hospitals that look
more for VTE with imaging studies find more VTE, thereby incorrectly seem to have
worse performance. However, these results have been questioned as the risk
adjustment and VTE measurement relied on administrative data. METHODS: Data (2009
2010) from 208 hospitals were available for analysis. Hospitals were divided into
quartiles according to VTE imaging use rates (Medicare claims). Observed and risk
adjusted postoperative VTE event rates (regression models using American College
of Surgeons National Surgical Quality Improvement Project data) were examined
across VTE imaging use rate quartiles. Multivariable linear regression models
were developed to assess the impact of hospital characteristics (American
Hospital Association) and hospital imaging use rates on VTE event rates. RESULTS:
The mean risk-adjusted VTE event rates at 30 days after surgery increased across
VTE imaging use rate quartiles: 1.13% in the lowest quartile to 1.92% in the
highest quartile (P < 0.001). This statistically significant trend remained when
examining only the inpatient period. Hospital VTE imaging use rate was the
dominant driver of hospital VTE event rates (P < 0.001), as no other hospital
characteristics had significant associations. CONCLUSIONS: Even when examined
with clinically ascertained outcomes and detailed risk adjustment, VTE rates
reflect hospital imaging use and perhaps signify vigilant, high-quality care. The
VTE outcome measure may not be an accurate quality indicator and should likely
not be used in public reporting or pay-for-performance programs.
PMID- 25115434
TI - CYP2C19*17 increases clopidogrel-mediated platelet inhibition but does not alter
the pharmacokinetics of the active metabolite of clopidogrel.
AB - The aim of the present study was to determine the impact of CYP2C19*17 on the
pharmacokinetics and pharmacodynamics of the active metabolite of clopidogrel and
the pharmacokinetics of proguanil. Thus, we conducted an open-label two-phase
cross-over study in 31 healthy male volunteers (11 CYP2C19*1/*1, 11 CYP2C19*1/*17
and nine CYP2C19*17/*17). In Phase A, the pharmacokinetics of the derivatized
active metabolite of clopidogrel (CAMD) and platelet function were determined
after administration of a single oral dose of 600 mg clopidogrel (Plavix; Sanofi
Avensis, Horsholm, Denmark). In Phase B, the pharmacokinetics of proguanil and
its metabolites cycloguanil and 4-chlorphenylbiguanide (4-CPB) were determined in
29 of 31 subjects after a single oral dose of 200 mg proguanil given as the
combination drug Malarone (GlaxoSmithKline Pharma, Brondby, Denmark). Significant
correlations were found between the area under the time-concentration curve (AUC0
infinity ) of CAMD and both the absolute ADP-induced P2Y12 receptor-activated
platelet aggregation (r = -0.60, P = 0.0007) and the percentage inhibition of
aggregation (r = 0.59, P = 0.0009). In addition, the CYP2C19*17/*17 and
CYP2C19*1/*17 genotype groups had significantly higher percentage inhibition of
platelet aggregation compared with the CYP2C19*1/*1 subjects (geometric mean
percentage inhibition of 84%, 73% and 63%, respectively; P = 0.014). Neither the
absolute ADP-induced P2Y12 receptor-activated platelet aggregation, exposure to
CAMD nor the pharmacokinetic parameters of proguanil, cycloguanil and 4-CPB
exhibited any significant differences among the genotype groups. In conclusion,
carriers of CYP2C19*17 exhibit higher percentage inhibition of platelet
aggregation, but do not have significantly lower absolute P2Y12 receptor
activated platelet aggregation or higher exposure to the active metabolite after
a single oral administration of 600 mg clopidogrel.
PMID- 25115433
TI - Nanoparticle-assisted targeted delivery of eye-specific genes to eyes
significantly improves the vision of blind mice in vivo.
AB - Application of viruses as a carrier, though not safe, to deliver genes to eye
tissue was successful. However, a safer, nonviral, biocompatible lipid-based
nanoparticle has never been tested to treat blinding eye diseases. We created an
artificial virus using a nanoparticle, liposome-protamine-DNA complex (LPD),
modified with a cell permeable peptide and a nuclear localization signaling (NLS)
peptide, to deliver a functional gene for eye disease treatment. In the eye, a
photochemical, 11-cis-retinal, allows the visual pigment rhodopsin to absorb
light in the visible range. Without the photochemical, we lose the ability to see
light. Retinal pigment epithelium protein 65 (Rpe65) is the key enzyme in
regulating the availability of photochemical; deficiency of this gene results in
a blinding eye disease. Here we show for the first time that LPD promotes
efficient delivery in a cell specific-manner, and a long-term expression of Rpe65
gene to mice lacking Rpe65 gene, leading to in vivo correction of blindness.
Thus, LPD nanoparticles could provide a promising, efficient, nonviral method of
gene delivery with clinical applications in eye disease treatment.
PMID- 25115436
TI - Latest evidence of the effects of the Mediterranean diet in prevention of
cardiovascular disease.
AB - The first step in the prevention of cardiovascular disease is healthy lifestyle
and diet. Recent systematic reviews of observational studies ranked Mediterranean
diet as the most likely dietary model to provide cardiovascular protection. This
review updates the knowledge on the effects of Mediterranean diet from
observational and randomized trials published in the last year. The results of
the PREDIMED study, a randomized trial providing a higher level of scientific
evidence than cohort studies, confirmed that the Mediterranean diet reduces the
incidence of cardiovascular events. This effect may be exerted by reducing blood
pressure; improving glucose metabolism, lipid profile, and lipoprotein particle
characteristics; and decreasing inflammation and oxidative stress. It may also
stem from a favorable interaction between diet and gene polymorphisms related to
cardiovascular risk factors and events. These recent results allow us to
recommend Mediterranean diet to subjects at high risk for cardiovascular disease
with the highest level of scientific evidence.
PMID- 25115435
TI - Expression of domains for protein-protein interaction of nucleotide excision
repair proteins modifies cancer cell sensitivity to platinum derivatives and
genomic stability.
AB - Nucleotide excision repair (NER) is involved in the repair of DNA damage caused
by platinum derivatives and has been shown to decrease the cytotoxic activity of
these drugs. Because protein-protein interactions are essential for NER activity,
we transfected human cancer cell lines (A549 and HCT116) with plasmids coding the
amino acid sequences corresponding to the interacting domains between excision
repair cross-complementation group 1 (ERCC1) and xeroderma pigmentosum,
complementation group A (XPA), as well as ERCC1 and xeroderma pigmentosum,
complementation group F (XPF), all NER proteins. Using the 3-(4,5-dimethyl-2
thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and annexin V staining,
we showed that transfected A549 cells were sensitized 1.2-2.2-fold to carboplatin
and that transfected HCT116 cells were sensitized 1.4-5.4-fold to oxaliplatin in
vitro. In addition, transfected cells exhibited modified in vivo sensitivity to
the same drugs. Finally, in particular cell models of the interaction between
ERCC1 and XPF, DNA repair was decreased, as evidenced by increased
phosphorylation of the histone 2AX after exposure to mitomycin C, and genomic
instability was increased, as determined by comparative genomic hybridization
studies. The results indicate that the interacting peptides act as dominant
negatives and decrease NER activity through inhibition of protein-protein
interactions.
PMID- 25115439
TI - Exacerbation of alopecia areata during pegylated interferon alpha-2b and
ribavirin therapy, possibly due to the collapse of hair follicle immune
privilege.
PMID- 25115438
TI - "Vitamin D supplementation and bone health in adults with diabetic nephropathy:
the protocol for a randomized controlled trial".
AB - BACKGROUND: Suboptimal vitamin D status is highly prevalent in Northern
communities, particularly in those patients with chronic diseases such as
diabetes and chronic renal disease. Emerging literature suggests that adherence
to daily vitamin D supplementation may be an important factor influencing vitamin
D status and overall bone health, but compliance with therapies for bone health
is a major challenge. It is unknown what level of vitamin D supplementation will
ameliorate or improve suboptimal vitamin D status in patients with diabetic
nephropathy or contribute to improved bone health, particularly for those living
in northern climates. METHODS/DESIGN: The study purpose was to examine two
different strategies of vitamin D3 supplementation; daily dosing of 2000 IU per
day verses monthly dosing of 40,000 IU per month on markers of vitamin D status,
bone health and to examine whether adherence, quality of life and patient
satisfaction with the supplementation strategy differs between the two vitamin D
strategies in adults diagnosed with diabetic nephropathy. DISCUSSION: The need
for RCTs assessing higher doses of vitamin D3 supplementation at varying
frequencies of administration and its impact on bone health in adults with
diabetes and chronic kidney disease are needed. TRIAL REGISTRATION:
ClinicalTrials.gov NCT01476501.
PMID- 25115437
TI - Untargeted metabolite profiling of murine embryos to reveal metabolic
perturbations associated with neural tube closure defects.
AB - BACKGROUND: Neural tube closure defects (NTDs) are among the most common
congenital malformation in human, typically presenting in liveborns as spina
bifida. At least 240 gene mutations in mouse are known to increase the risk of
NTD. There is a growing appreciation that environmental factors significantly
contribute to NTD expression, and that NTDs likely arise from complex gene
environment interactions. Because maternal folic acid supplementation reduces
human NTD risk in some populations by 60 to 70%, it is likely that NTD
predisposition is often associated with a defect in folate-dependent one-carbon
metabolism. A comprehensive, untargeted metabolic survey of NTD-associated
changes in embryo metabolism would provide a valuable test of this assumption. We
sought to establish a metabolic profiling platform that is capable of broadly
assessing metabolic aberrations associated with NTD-promoting gene mutations in
early-stage mouse embryos. METHODS: A liquid chromatography/mass spectrometry
based untargeted metabolite profiling platform was used to broadly identify
significant differences in small molecule levels (50-1000 Da) in NTD-affected
embryonic day (E) 9.5 mouse embryos (Lrp6(-) (/) (-) ) versus unaffected
(Lrp6(+/+) ) control embryos. RESULTS: Results provide proof-of-principal
feasibility for the broad survey of the metabolome of individual E9.5 mouse
embryos and identification of metabolic changes associated with NTDs and gene
mutations. Levels of 30 different metabolites were altered in association with
Lrp6 gene deletion. Some metabolites link to folate-dependent one-carbon transfer
reactions, as anticipated, while others await structure elucidation and pathway
integration. CONCLUSION: Whole-embryo metabolomics offers the potential to
identify metabolic changes in genetically determined NTD-prone embryos.
PMID- 25115440
TI - Wntless (GPR177) expression correlates with poor prognosis in B-cell precursor
acute lymphoblastic leukemia via Wnt signaling.
AB - B-cell precursor acute lymphoblastic leukemia (BCP ALL) is the most common
childhood leukemia, with a cure rate of 80%. Nevertheless, disease relapse is the
most important prognostic factor for the disease outcome. We aimed to elucidate
the role of Wnt secretion-regulating protein, Wntless (Wls)/GPR177, on disease
outcome in pediatric patients with BCP ALL, and assess its pathogenetic role in
the regulation of the disease. Wls expression was characterized and correlated
with Wnt pathway signaling in the bone marrow leukemia cells isolated from 44
pediatric patients with BCP ALL. The overexpression of Wls was detected in
leukemia cells and was significantly correlated with the disease relapse and poor
survival in the patients. The high expression of Wls also correlated with the Wnt
expression and consequent downstream signaling activation, which was shown to
provide essential proliferation, transformation and anti-apoptotic activity
during leukemogenesis. These results indicated that Wls played an essential role
in disease relapse and poor survival in patients with BCP ALL. Therefore, Wls may
provide a potential future therapeutic target, particularly for patients who do
not respond to existing therapies and suffer relapse.
PMID- 25115441
TI - Approaches to integrating germline and tumor genomic data in cancer research.
AB - Cancer is characterized by a diversity of genetic and epigenetic alterations
occurring in both the germline and somatic (tumor) genomes. Hundreds of germline
variants associated with cancer risk have been identified, and large amounts of
data identifying mutations in the tumor genome that participate in tumorigenesis
have been generated. Increasingly, these two genomes are being explored jointly
to better understand how cancer risk alleles contribute to carcinogenesis and
whether they influence development of specific tumor types or mutation profiles.
To understand how data from germline risk studies and tumor genome profiling is
being integrated, we reviewed 160 articles describing research that incorporated
data from both genomes, published between January 2009 and December 2012, and
summarized the current state of the field. We identified three principle types of
research questions being addressed using these data: (i) use of tumor data to
determine the putative function of germline risk variants; (ii) identification
and analysis of relationships between host genetic background and particular
tumor mutations or types; and (iii) use of tumor molecular profiling data to
reduce genetic heterogeneity or refine phenotypes for germline association
studies. We also found descriptive studies that compared germline and tumor
genomic variation in a gene or gene family, and papers describing research
methods, data sources, or analytical tools. We identified a large set of tools
and data resources that can be used to analyze and integrate data from both
genomes. Finally, we discuss opportunities and challenges for cancer research
that integrates germline and tumor genomics data.
PMID- 25115442
TI - Granulin-epithelin precursor interacts with heparan sulfate on liver cancer
cells.
AB - Granulin-epithelin precursor (GEP) is a pluripotent secretory growth factor which
promotes cancer progression in a number of human cancers. However, how cancer
cells interact with GEP remains unknown. In this study, we aimed to identify the
cell surface-binding partner of GEP on liver cancer cells. Human recombinant GEP
(rGEP) was expressed and purified to homogeneity. The rGEP was shown to trigger
phosphorylation of AKT and ERK1/2 in liver cancer cells. We demonstrated cell
surface attachment of rGEP, which was blocked by prebinding of platelet-derived
growth factor-AA, platelet-derived growth factor-BB and fibroblast growth factor
2. Therefore, heparan sulfate (HS) had been reasoned as the binding partner of
rGEP. Heparinase digestion validated the role of HS on supporting the attachment.
The heparin-binding domain of GEP was mapped to RRH(555-557) in the C-terminal
region. Suppression of the HS polymerase exostosin-1 reduced the rGEP binding and
rGEP-mediated signaling transduction. Suppression of a specific HS proteoglycan,
glypican-3, also showed a partial reduction of rGEP binding and an inhibition on
rGEP-mediated activation of AKT. Furthermore, glypican-3 was shown to correlate
with the expressions of GEP in clinical samples (Spearman's rho = 0.363, P =
0.001). This study identified HS, partly through glypican-3, as a novel binding
partner of GEP on the surface of liver cancer cells.
PMID- 25115444
TI - Blood cadmium and depressive symptoms in young adults (aged 20-39 years).
AB - BACKGROUND: Genetic and environmental factors contribute to the risk of
depression and several studies have noted an association between tobacco smoke
and depression. Cadmium is a neurotoxicant and the main source of non
occupational exposure is tobacco smoke. METHOD: We conducted a cross-sectional
analysis of data from 2892 young adult (aged 20-39 years) participants of the
National Health and Nutrition Examination Survey (NHANES) 2007-2010. Multivariate
logistic regressions, adjusted for age, sex, race/ethnicity, education, poverty
income ratio (PIR), obesity, alcohol intake, blood lead (BPb) and smoking status,
were used to analyze the association between blood cadmium (BCd) and depressive
symptoms, as determined by the score on the nine-item Patient Health
Questionnaire (PHQ-9). RESULTS: Individuals in the highest BCd quartile had
higher odds of having depressive symptoms [odds ratio (OR) 2.79, 95% confidence
interval (CI) 1.84-4.25] than those in the lowest BCd quartile. Smoking status,
but not BPb, was statistically significantly associated with depressive symptoms.
Stratification by smoking status found that BCd was significantly associated with
depressive symptoms in both non-smokers (OR 2.91, 95% CI 1.12-7.58) and current
smokers (OR 2.69, 95% CI 1.13-6.42). CONCLUSIONS: This is the first study to
report an association between BCd levels and depressive symptoms using a
nationally representative sample. The association of cadmium with depressive
symptoms was independent of smoking status. If this association is further
confirmed, the continued efforts at reducing cadmium exposures, mainly through
tobacco smoking cessation programs, may decrease the incidence of depression.
PMID- 25115445
TI - The role of mirabegron in overactive bladder: a systematic review and meta
analysis.
AB - OBJECTIVE: To present a systematic review assessing the efficacy and safety of
mirabegron for overactive bladder (OAB). MATERIALS AND METHODS: A literature
search was performed using the Cochrane Library, MEDLINE, EMBASE and Science
Citation Index Expanded. The literature reviewed included meta-analyses,
randomized and nonrandomized prospective studies. We utilized mean difference
(MD) to measure the mean number of incontinence episodes and the mean number of
micturitions, and OAB questionnaire (OAB-q) and odds ratio (OR) to measure
adverse events rates. We used the Cochrane Collaboration's Review Manager 5.1
software for statistical analysis. RESULTS: We identified six publications that
strictly met our eligibility criteria. Meta-analysis of extractable data showed
that mirabegron was more effective than placebo in treating OAB despite different
drug dosages in the efficacy end points: mean number of incontinence episodes per
24 h (MD -0.54; 95% CI -0.63, -0.45; p = 0.001), mean number of micturitions per
24 h (MD -0.55; 95% CI -0.63, -0.47; p = 0.001), OAB-q (MD -4.49; 95% CI -6.27,
2.71; p = 0.001) and adverse events (OR 0.99; 95% CI 0.83, 1.19; p = 0.92). When
compared to tolterodine, mirabegron was more effective in terms of mean number of
incontinence episodes per 24 h (MD -0.25; 95% CI -0.43, -0.06; p = 0.009).
However, there were no differences between mirabegron and tolterodine in mean
number of micturitions per 24 h (MD -0.17; 95% CI -0.35, 0.01; p = 0.07) and OAB
q (MD -1.09; 95% CI -2.51, 0.33; p = 0.13). Mirabegron also had a lower adverse
reaction rate (OR 0.9; 95% CI 0.8, 1.0; p = 0.04). CONCLUSIONS: In this diverse
population, mirabegron was an effective and safe pharmacologic therapy for OAB.
PMID- 25115443
TI - N-methylnicotinamide and nicotinamide N-methyltransferase are associated with
microRNA-1291-altered pancreatic carcinoma cell metabolome and suppressed
tumorigenesis.
AB - The cell metabolome comprises abundant information that may be predictive of cell
functions in response to epigenetic or genetic changes at different stages of
cell proliferation and metastasis. An unbiased ultra-performance liquid
chromatography-mass spectrometry-based metabolomics study revealed a
significantly altered metabolome for human pancreatic carcinoma PANC-1 cells with
gain-of-function non-coding microRNA-1291 (miR-1291), which led to a lower
migration and invasion capacity as well as suppressed tumorigenesis in a
xenograft tumor mouse model. A number of metabolites, including N
methylnicotinamide, involved in nicotinamide metabolism, and l-carnitine,
isobutyryl-carnitine and isovaleryl-carnitine, involved in fatty acid metabolism,
were elevated in miR-1291-expressing PANC-1. Notably, N-methylnicotinamide was
elevated to the greatest extent, and this was associated with a sharp increase in
nicotinamide N-methyltransferase (NNMT) mRNA level in miR-1291-expressing PANC-1
cells. In addition, expression of NNMT mRNA was inversely correlated with
pancreatic tumor size in the xenograft mouse model. These results indicate that
miR-1291-altered PANC-1 cell function is associated with the increase in N
methylnicotinamide level and NNMT expression, and in turn NNMT may be indicative
of the extent of pancreatic carcinogenesis.
PMID- 25115447
TI - Anti-adalimumab antibodies and adalimumab concentrations in psoriatic arthritis;
an association with disease activity at 28 and 52 weeks of follow-up.
AB - OBJECTIVES: To investigate the relationship between antidrug antibodies (ADA),
adalimumab concentrations and clinical response in patients with psoriatic
arthritis (PsA) during 52 weeks of follow-up. METHODS: This prospective cohort
study included 103 consecutive patients with PsA. Disease Activity Score of 28
joints (DAS28), Erythrocyte Sedimentation Rate, C reactive protein and Psoriasis
Area and Severity Index were assessed. Adalimumab concentrations and ADA were
measured in serum trough samples, using an ELISA and a radio immunoassay,
respectively. RESULTS: Adalimumab concentrations were significantly lower at 28
and 52 weeks in patients with detectable ADA compared with patients without
detectable ADA (at week 28: 1.3 mg/L (IQR 0.0-3.2) versus 8.7 mg/L (IQR 5.7
11.5), p<0.001; at week 52: 0.9 mg/L (IQR 0.0-2.9) vs 9.4 mg/L (IQR 5.7-12.1),
p=0.0001). DAS28 at 28 weeks (2.16 vs 2.95, p=0.023) and 52 weeks (2.19 vs 2.95,
p=0.024) showed a significant difference; patients with detectable ADA had a
poorer clinical outcome than patients without. CONCLUSIONS: Patients with
detectable ADA had lower adalimumab concentrations and a significantly poorer
clinical outcome compared with patients in whom ADA were not detected.
PMID- 25115448
TI - Additive effect of anti-citrullinated protein antibodies and rheumatoid factor on
bone erosions in patients with RA.
AB - OBJECTIVE: To determine whether there is an additive effect of anticitrullinated
protein antibodies (ACPA) and rheumatoid factor (RF) on the number and size of
bone erosions in patients with rheumatoid arthritis (RA) METHODS: 242 patients
with RA received high-resolution peripheral quantitative CT (HR-pQCT) scans of
the metacarpophalangeal joints. Demographic and disease-specific parameters
including ACPA and RF levels were recorded from all patients. Erosion numbers and
their size were assessed in 238 patients at 714 individual joints (MCP 2, 3 and
4) and 5712 sites (each 4 quadrants in metacarpal heads and phalangeal bases).
The volume of erosions was calculated by a semiellipsoid formula. RESULTS: Of the
238 patients, 112 patients showed RF and ACPAs (ACPAs+RF+), 28 only RF (RF+), 29
only ACPAs (ACPA+) and 69 were antibody negative (NEG). Erosion number and size
were highest in RF+ACPAs+ patient group with significant differences compared
with NEG patients with respect to erosion number (p=0.001) and to ACPA-negative
patients with respect to erosion size (p<0.001). Results maintained significance
in a linear mixed model showing ACPAs+RF+ status and disease duration being
associated with higher number (p=0.017 and p=0.005, respectively), and larger
size (p=0.014 and p=0.013, respectively) of bone erosions. Furthermore, erosion
size was influenced by the presence and titre of RF only in ACPA-positive
patients with RA but not in ACPA-negative patients. CONCLUSIONS: ACPAs and RF
show an additive effect on erosion number and erosion size. Concomitant presence
of ACPAs and RF is associated with higher erosive disease burden in patients with
RA. Furthermore, RF influences erosion size only in ACPA-positive but not in ACPA
negative patients.
PMID- 25115450
TI - Of text and gene--using text mining methods to uncover hidden knowledge in
toxicogenomics.
AB - BACKGROUND: Toxicogenomics studies often profile gene expression from assays
involving multiple doses and time points. The dose- and time-dependent pattern is
of great importance to assess toxicity but computational approaches are lacking
to effectively utilize this characteristic in toxicity assessment. Topic modeling
is a text mining approach, but may be used analogously in toxicogenomics due to
the similar data structures between text and gene dysregulation. RESULTS: Topic
modeling was applied to a very large toxicogenomics dataset containing microarray
gene expression data from >15,000 samples associated with 131 drugs tested in
three different assay platforms (i.e., in vitro assay, in vivo repeated dose
study and in vivo single dose experiment) with a design including multiple doses
and time points. A set of "topics" which each consist of a set of genes was
determined, by which the varying sensitivity of three assay systems was observed.
We found that the drug-dependent effect was more pronounced in the two in vivo
systems than the in vitro system, while the time-dependent effect was most
strongly reflected in the in vitro system followed by the single dose study and
lastly the repeated dose experiment. The dose-dependent effect was similar across
three assay systems. Although the results indicated a challenge to extrapolate
the in vitro results to the in vivo situation, we did notice that, for some drugs
but not for all the drugs, the similarity in gene expression patterns was
observed across all three assay systems, indicating a possibility of using in
vitro systems with careful designs (such as the choice of dose and time point),
to replace the in vivo testing strategy. Nonetheless, a potential to replace the
repeated dose study by the single-dose short-term methodology was strongly
implied. CONCLUSIONS: The study demonstrated that text mining methodologies such
as topic modeling provide an alternative method compared to traditional means for
data reduction in toxicogenomics, enhancing researchers' capabilities to
interpret biological information.
PMID- 25115449
TI - Insights into the poor prognosis of allopurinol-induced severe cutaneous adverse
reactions: the impact of renal insufficiency, high plasma levels of oxypurinol
and granulysin.
AB - OBJECTIVE: Allopurinol, an antihyperuricaemic agent, is one of the common causes
of life-threatening severe cutaneous adverse reactions (SCAR), including drug
rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome
(SJS) and toxic epidermal necrosis (TEN). The prognostic factors for allopurinol
related SCAR remain unclear. This study aimed to investigate the relationship of
dosing, renal function, plasma levels of oxypurinol and granulysin (a cytotoxic
protein of SJS/TEN), the disease severity and mortality in allopurinol-SCAR.
METHODS: We prospectively enrolled 48 patients with allopurinol-SCAR (26 SJS/TEN
and 22 DRESS) and 138 allopurinol-tolerant controls from 2007 to 2012. The human
leucocyte antigen (HLA)-B*58:01 status, plasma concentrations of oxypurinol and
granulysin were determined. RESULTS: In this cohort, HLA-B*58:01 was strongly
associated with allopurinol-SCAR (p<0.001, OR (95% CI) 109 (25 to 481)); however,
the initial/maintenance dosages showed no relationship with the disease. Poor
renal function was significantly associated with the delayed clearance of plasma
oxypurinol, and increased the risk of allopurinol-SCAR (p<0.001, OR (95% CI) 8.0
(3.9 to 17)). Sustained high levels of oxypurinol after allopurinol withdrawal
correlated with the poor prognosis of allopurinol-SCAR. In particular, the
increased plasma levels of oxypurinol and granulysin linked to the high mortality
of allopurinol-SJS/TEN (p<0.01), and strongly associated with prolonged cutaneous
reactions in allopurinol-DRESS (p<0.05). CONCLUSIONS: Impaired renal function and
increased plasma levels of oxypurinol and granulysin correlated with the poor
prognosis of allopurinol-SCAR. Allopurinol prescription is suggested to be
avoided in subjects with renal insufficiency and HLA-B*58:01 carriers. An early
intervention to increase the clearance of plasma oxypurinol may improve the
prognosis of allopurinol-SCAR.
PMID- 25115451
TI - Enhanced aqueous dissolution of a DNAPL source to characterize the source
strength function.
AB - Simplified analytical solutions, developed as source strength functions (SSFs),
are capable of describing the temporal dissolution of nonaqueous phase liquids in
groundwater, which is useful for predicting source longevity and can serve as a
guide for remedial activities. Here, SSF parameters were estimated by fitting
enhanced aqueous dissolution data from a flow cell consisting of three injection
and four extraction wells to analytical dissolution models (power law model (PLM)
and equilibrium streamtube model (EST)) at a trichloroethene (TCE) contaminated
site, Alameda Point, California. Both the PLM and the EST model were able to
characterize the observed aqueous TCE dissolution during enhanced water flooding.
Additional field activities conducted at the site included soil core collection,
a recirculated partitioning tracer test, passive flux meter transects, and push
pull tracer tests. The additional site characterization data were used to
independently estimate the observed SSF parameters using information such as the
TCE mass, distribution and porous media heterogeneity. The exponential decay
model (a subset of the PLM) accurately predicted the enhanced dissolution, likely
because the site was significantly aged (most of the mass in the plume rather
than in the source zone) or middle stage, and the mass in the source zone could
be approximately estimated. The EST tracer-based model, when combined with data
from the recirculated partitioning tracer test, soil cores, and the push-pull
tracer test, was capable of accurately predicting the observed aqueous
dissolution. The mass in the source zone and the fraction of contaminated
flowpaths were the most important site characteristics, requiring the greatest
accuracy to predict aqueous dissolution. Establishing steady state dissolution
was essential to provide a more accurate estimate of the fraction contaminated
and high resolution data from soil cores in the source zone were needed to
estimate the mass present.
PMID- 25115452
TI - Photoinduced skeletal rearrangement of diarylethenes comprising oxazole and
phenyl rings.
AB - A novel photochemical rearrangement of diarylethenes bearing oxazole and benzene
derivatives as aryl moieties that results in the formation of polyaromatic
systems was investigated. The mechanism of the transformation includes
photocyclization, sequential [1,9] and [1,3]-hydrogen shifts, as well as a
lateral oxazole ring-opening process. It was shown that this reaction can be an
effective synthetically preparative method for the preparation of naphthalene
(polyaromatic) derivatives.
PMID- 25115453
TI - Quality improvements of cell membrane chromatographic column.
AB - Cell Membrane Chromatography (CMC) is a biological affinity chromatographic
method using a silica stationary phase covered with specific cell membrane.
However, its short life span and poor quality control was highlighted in a lot of
research articles. In this study, special attention has been paid to the
disruption, cell load and packing procedure in order to improve the quality of
the CMC columns. Hereto, two newly established CMC models, HSC-T6/CMC and SMMC
7721/CMC have been developed and used in this research project. The optimization
of the abovementioned parameters resulted in a better reproducibility of the
retention time of the compound GFT (RSD<10%) and improved significantly the
quality of the CMC columns. 3.5*10(7)cells were the optimal cell load for the
preparation of the CMC columns, the disruption condition was optimized to 5
cycles (400W and 20s interval per cycle) by an ultrasonic processor reducing the
total time of cell disruption to 1.5min and the packing flow rate was optimized
by applying a linear gradient program. Additionally, 4% paraformaldehyde (PFA)
was employed to improve the column quality and prolong the column life span. The
results showed that the retention time was longer with PFA treated columns than
the ones obtained with the control groups.
PMID- 25115454
TI - Alternative sorbents for the dispersive solid-phase extraction step in quick,
easy, cheap, effective, rugged and safe method for extraction of pesticides from
rice paddy soils with determination by liquid chromatography tandem mass
spectrometry.
AB - The clean-up step is essential to reduce interferences, improve quantification
and help to maintain the integrity of the chromatographic system when working
with complex matrices. In this study, alternative materials were evaluated as
sorbents in the dispersive solid-phase extraction (D-SPE) for the determination
and extraction of seventeen pesticides from rice paddy soil samples by the quick,
easy, cheap, effective, rugged and safe (QuEChERS) method coupled with liquid
chromatography-tandem mass spectrometry (LC-MS/MS). Chitin, chitosan,
diatomaceous earth and PSA were compared in terms of extraction efficiency and
matrix effect. The best results were achieved when chitosan was used.
Quantification limits ranged from 0.1 to 100MUgkg(-1). Calibration curves showed
correlation coefficient values higher than 0.98. Results of accuracy and
precision in the spiked soil samples between 60% and 120%, with a relative
standard deviation lower than 20%, were reached for 15 out of 17 pesticides. The
matrix effect was evaluated and only one compound was influenced by the matrix
components, showing medium effect. Results showed that alternative materials are
more effective and less expensive than traditional sorbents which have been
usually employed, i.e., they may be used in the D-SPE step during the extraction
of pesticides from rice paddy soils.
PMID- 25115455
TI - 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride as an
enantioseparation enhancer for fluorescence chiral derivatization-liquid
chromatographic analysis of dl-lactic acid.
AB - This paper reports a novel fluorescence chiral derivatization-liquid
chromatography (LC) method for the analysis of d- and l-lactic acids (LAs) using
4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) as an
enantioseparation enhancer. In this method, the dl-LAs were fluorescently
derivatized with (S)-(+)-4-(N,N-dimethylaminosulfonyl)-7-(3-aminopyrrolidin-1-yl)
2,1,3-benzoxadiazole [(S)-(+)-DBD-APy] in the presence of DMT-MM as a condensing
agent. These conditions resulted in the hydroxyl group of the LA derivative being
etherified by the triazine unit of DMT-MM, producing sterically bulky
diastereoisomers. The resulting fluorescent diastereoisomers of d- and l-LAs
could be discriminated and successfully enantioseparated through reversed-phase
LC. The enhancement effect of the derivatization agent DMT-MM when using seven
other commercially available chiral amines was also demonstrated. Finally, this
method was successfully applied to quantification of dl-LAs in foodstuffs
(yogurts and fermented milk drinks).
PMID- 25115456
TI - Simple semi-automated portable capillary electrophoresis instrument with
contactless conductivity detection for the determination of beta-agonists in
pharmaceutical and pig-feed samples.
AB - An inexpensive, robust and easy to use portable capillary electrophoresis
instrument with miniaturized high-voltage capacitively coupled contactless
conductivity detection was developed. The system utilizes pneumatic operation to
manipulate the solutions for all flushing steps. The different operations, i.e.
capillary flushing, interface rinsing, and electrophoretic separation, are easily
activated by turning an electronic switch. To allow the analysis of samples with
limited available volume, and to render the construction less complicated
compared to a computer-controlled counterpart, sample injection is carried out
hydrodynamically directly from the sample vial into the capillary by manual
syphoning. The system is a well performing solution where the financial means for
the highly expensive commercial instruments are not available and where the in
house construction of a sophisticated automated instrument is not possible due to
limited mechanical and electronic workshop facilities and software programming
expertise. For demonstration, the system was employed successfully for the
determination of some beta-agonists, namely salbutamol, metoprolol and
ractopamine down to 0.7ppm in pharmaceutical and pig-feed sample matrices in
Vietnam.
PMID- 25115457
TI - Hecogenin acetate inhibits reactive oxygen species production and induces cell
cycle arrest and senescence in the A549 human lung cancer cell line.
AB - Cellular and molecular mechanisms related to lung cancer have been extensively
studied in recent years, but the availability of effective treatments is still
scarce. Hecogenin acetate, a natural saponin presenting a wide spectrum of
reported pharmacological activities, has been previously evaluated for its
anticancer/antiproliferative activity in some in vivo and in vitro models. Here,
we investigated the effects of hecogenin acetate in a human lung cancer cell
line. A549 non-small lung cancer cells were exposed to different concentrations
of hecogenin acetate and reactive species production, ERK1/2 activation, matrix
metalloproteinase expression, cell cycle arrest and cell senescence parameters
were evaluated. Hecogenin acetate significantly inhibited increase in
intracellular reactive species production induced by H2O2. In addition, hecogenin
acetate blocked ERK1/2 phosphorylation and inhibited the increase in MMP-2 caused
by H2O2. Treatment with hecogenin acetate induced G0/G1-phase arrest at two
concentrations (75 and 100 uM, 74% and 84.3% respectively), and increased the
staining of senescence-associated beta -galactosidase positive cells. These data
indicate that hecogenin acetate is able to exert anti-cancer effects by
modulating reactive species production, inducing cell cycle arrest and senescence
and also modulating ERK1/2 phosphorylation and MMP-2 production.
PMID- 25115458
TI - Association between rs12970134 Near MC4R and adiposity indexes in a homogenous
population of Caucasian schoolchildren.
AB - BACKGROUND: To assess whether previously identified obesity-susceptibility loci
were associated with overweight/obesity risk in a homogeneous population of
Caucasian schoolchildren and whether these associations varied with age. METHODS:
Seven hundred and forty-five schoolchildren (353 boys, mean age: 8.3 +/- 1.4
years) underwent anthropometric assessments. A saliva sample was collected for
DNA extraction and assessment of 19 single-nucleotide polymorphisms previously
associated with obesity. RESULTS: Only the rs12970134 in the MC4R gene was
significantly associated with overweight/obesity risk, with a higher frequency of
the AA risk genotype in children with a BMI >85th (8.3%) than in those with a BMI
<85th percentile (3.0%), p = 0.001; odds ratio (95% CI) of 1.544 (1.192-1.998), p
= 0.001, after adjusting for age, sex and pubertal stage. BMI standard deviation
scores (SDS) and waist-to-height ratio (W/Hr) progressively increased across the
rs12970134 genotypes (GG vs. AG vs. AA): BMI SDS, p = 0.004; W/Hr, p = 0.009.
When dividing the study population into two groups based on the median age of
participants (8.3 years), the differences in BMI SDS and W/Hr across the MC4R
genotypes persisted only in children older than 8.3 years. CONCLUSIONS: In a
population of Caucasian schoolchildren, the rs12970134 MC4R variant was
significantly associated with excess body weight, particularly in children older
than 8 years of age.
PMID- 25115459
TI - Propofol versus traditional sedative agents for endoscopic submucosal dissection.
AB - BACKGROUND AND AIM: Propofol has been suggested to be superior to benzodiazepines
when used as a sedative agent for endoscopic examination. The aim of the present
study was to systematically evaluate the safety and efficacy of propofol sedation
for endoscopic submucosal dissection (ESD). METHODS: PubMed, the Cochrane
library, and the Igaku-Chuo-Zasshi database were searched in order to identify
randomized trials eligible for inclusion in the systematic review. Data from the
eligible studies were combined to calculate pooled odds ratios (OR) of developing
restlessness, full awakening at 1 h post-ESD, hypoxia, and hypotension. RESULTS:
We identified three randomized trials (298 patients) from the database search.
Compared with traditional sedative agents, the pooled OR of restlessness and full
awakening at 1 h post-ESD with propofol sedation were 0.41 (95% confidence
interval [CI]: 0.21-0.81) and 8.59 (95% CI: 4.29-17.2), respectively, without
significant heterogeneity. Compared with traditional sedative agents, the pooled
OR of hypoxia and hypotension with propofol sedation were 1.13 (95% CI: 0.58
2.21) and 0.92 (95% CI: 0.25-3.41), respectively, indicating no significant
differences between the groups. CONCLUSION: Propofol sedation during ESD is more
effective as compared with traditional sedative agent. The risk of complications
is similar.
PMID- 25115460
TI - A systematic review of online youth mental health promotion and prevention
interventions.
AB - The rapid growth in the use of online technologies among youth provides an
opportunity to increase access to evidence-based mental health resources. The aim
of this systematic review is to provide a narrative synthesis of the evidence on
the effectiveness of online mental health promotion and prevention interventions
for youth aged 12-25 years. Searching a range of electronic databases, 28 studies
conducted since 2000 were identified. Eight studies evaluating six mental health
promotion interventions and 20 studies evaluating 15 prevention interventions
were reviewed. The results from the mental health promotion interventions
indicate that there is some evidence that skills-based interventions presented in
a module-based format can have a significant impact on adolescent mental health,
however, an insufficient number of studies limits this finding. The results from
the online prevention interventions indicate the significant positive effect of
computerized cognitive behavioral therapy on adolescents' and emerging adults'
anxiety and depression symptoms. The rates of non-completion were moderate to
high across a number of studies. Implementation findings provide some evidence
that participant face-to-face and/or web-based support was an important feature
in terms of program completion and outcomes. Additional research examining
factors affecting exposure, adherence and outcomes is required. The quality of
evidence across the studies varied significantly, thus highlighting the need for
more rigorous, higher quality evaluations conducted with more diverse samples of
youth. Although future research is warranted, this study highlights the potential
of online mental health promotion and prevention interventions in promoting youth
wellbeing and reducing mental health problems.
PMID- 25115461
TI - Two cases of ulcerative colitis developing in rheumatoid arthritis patients
during abatacept therapy.
PMID- 25115462
TI - Collagen-functionalised titanium surfaces for biological sealing of dental
implants: effect of immobilisation process on fibroblasts response.
AB - The clinical success of a dental implant requires not only an optimum
osseointegration, but also the development of a biological sealing; i.e., a soft
tissue seal around the transmucosal part of the implant. A promising approach to
improve the biological seal of dental implants is the biomimetic modification of
titanium surfaces with proteins or peptides that have specific cell-binding
moieties. In this work we investigated the process of immobilising collagen on
smooth and rough titanium surfaces and its effect on human dermal fibroblast
(HDF) cell response. Titanium samples were activated by either oxygen plasma or
acid etching to generate a smooth or nanorough surface, respectively.
Subsequently, collagen grafting was achieved by either physisorption or covalent
bonding through organosilane chemistry. The biofunctionalised titanium samples
were then tested for stability and characterised by fluorescent labelling,
wettability, OWLS and XPS studies. Biological characterisation was also performed
through HDF adhesion, proliferation and gene expression. Covalent-bonded collagen
showed higher stability than physisorbed collagen. A significant overexpression
of the genes involved in fibroblast activation and extracellular matrix
remodelling was observed in the collagen-coated surfaces. This effect was more
pronounced on smooth than on rough surfaces. Immobilised collagen on the smooth
plasma-treated surfaces favoured both fibroblast adhesion and activation. This
study provides essential information for the design of implants with optimal
biological sealing, a key aspect to avoid peri-implantitis and ensure long
lasting implant fixation.
PMID- 25115463
TI - [Women are more sedentary than men: are they lazy or discriminated?].
PMID- 25115464
TI - [The epidemiologists and the participant-led science].
PMID- 25115465
TI - [Who is monitoring air pollution in Florence?].
PMID- 25115466
TI - [Science and law in courts].
AB - Science and law can be seen as the main creators of orders and rules in knowledge
based societies. These relations are particularly delicate in domains where
scientific uncertainty and probabilistic causality are more frequently involved,
such as environment and health. The decision of the Court of Florence (Tuscany
Region, Northern Italy) (Second Criminal Division, 3217/2010, 17th May 2010) -
here analysed - deals with the uncertain correlations between PM10 and health.
The criminal law case involved some public officers in Tuscany, indicted for
having failed to adopt the adequate measures to keep PM10 levels within the
limits set by European Directive 2008/50/EC on air quality. In arguing that
accusations were ill-founded, the Court, while invoking the validity of science,
deliberately chose the scientific evidence relevant to drawing specific legal
consequences. Meteorological phenomena are considered as the single determinant
of high levels of PM10; their uncertainty is framed as absolute unpredictability
and ungovernability, and from these flaws non-responsibility. The concept of
coproduction is applied as a useful critical tool to open up the complex
relationships between science and law by showing how scientific and legal
concepts generate and influence each other even when legal regulations claims to
be neutrally and objectively science-based.
PMID- 25115467
TI - [Noise and air pollution: the effect of airports on the health of residents].
PMID- 25115468
TI - [Relationship between surgical volumes and 30-day mortality in patients with
oesophagus and stomach cancer: a review of the literature and metanalysis].
AB - OBJECTIVES: to analyse the relationship between annual hospital volumes of
surgery for oesophageal and gastric cancer and 30-day mortality. DESIGN: a
systematic review of the literature has been carried out on these topics by
searching Medline for the years 1998-2012 and using two ad hoc search strings.
For oesophageal cancer, the most recent and best quality systematic review was
updated by including further studies, and then a metanalysis was carried out. For
gastric cancer, two different metanalyses on low and high volumes were performed.
RESULTS: regarding oesophageal carcinoma, the study confirmed the association
between 30-day mortality and the number of annual hospital interventions for this
pathology. As for stomach cancer, the two metanalyses confirmed the role of high
volume surgery in reducing the outcome considered. CONCLUSIONS: this study
confirms the association between short-term outcomes and the number of annual
hospital interventions for oesophageal and gastric cancer. The results obtained
may be important for health care policy makers and administrators/managers in
order to improve quality of care for patients with oesophageal or stomach cancer.
PMID- 25115469
TI - [Avoidable mortality in Tuscany Region (Central Italy) from 1987 to 2008].
AB - OBJECTIVE: to evaluate the impact of avoidable mortality (AM) on the changes in
life expectancy at birth (LE) in Tuscany Region (Central Italy) in two periods
(1987-1989 and 2006-2008). SETTING AND PARTICIPANTS: a list of AM causes
previously published was used. The AM were divided into two groups: AM by Health
Policy Interventions (HPI), AM by Health System Interventions (HSI). MAIN OUTCOME
MEASURES: years of potential life lost (PYLLs), rates of PYLL standardized on the
European population (TSPYLLs), and LE were examined. RESULTS: in 2006-2008, LE
increased with a gain of 5.2 in men and 3.8 in women in comparison to 1987-1989
LE (respectively 79 and 84,9 years). If AM did not have occurred, LE would have
further increased of 2 years in men and 1.5 in women. AM recorded a 39% decrease:
from 25.3% of overall mortality in men in 1987-1989 to 16.1% in 2006-2008; in
women from 14.3% to 8.4%. Injury/poisoning and lung cancer are the most frequent
IPP. The only increasing AM is lung cancer in women. Disentangling LE increases
by group of causes, 25% of the increases in 2006- 2008, compared to 1987-1989,
was attributable to HSI reduction, and 4% in women and 16% in men to HPI
reduction. CONCLUSIONS: AM recorded a 39% decrease from 1987-1989 to 2006-2008 in
Tuscany. In 2006-2008, about one third of LE increase in women and 2/5 in men was
attributable to AM decrease, while 2/3 in women and 3/5 in men to increased
survival in eldest people.
PMID- 25115470
TI - [Tuberculosis in the districts of Kamez and Vlore (Albania) in the early 2000s].
AB - OBJECTIVES: evaluation of tuberculosis (TB) rates and treatment outcomes in two
Albanian districts of similar population, but different disease diffusion: Kamez
and Vlore. DESIGN AND PARTICIPANTS: retrospective observational study of all the
medical charts of not-HIV+ TB patients in Vlore from 2002 to 2011, and in Kamez
from 2004 to 2011. MAIN OUTCOME MEASURES AND RESULTS: at Vlore the cases observed
were 120 cases (mean age: 43 years, 68% males); the incidence rate was
substantially stable in the study period, with 8 cases/100,000 inhabitants/year,
and, overall, lower (p <0.001) than at Kamez. The TB cases founded were 160 (mean
age: 45 years, 61% males) at Kamez, with decreasing incidence rate (Annual
Percent Change - APC: -12%; p =0.00022), from 30-42/100,000 inhabitants/year in
2004- 2005 to 16.4/100,000 in 2011. New and retreated cases were, respectively,
96.7% and 3.3% at Vlore, and 96.25% and 3.75% at Kamez. Pulmonary TB was 75% at
Vlore and 65% at Kamez. Most cases with pulmonary TB (79%) were microbiologically
confirmed. Overall, successful treatments and relapses were respectively observed
in 89% and 3% of cases with no drug resistance CONCLUSIONS: in the first years of
the third millennium, TB rates remain different between the two studied Albanian
districts, but with a significant reduction in the area with greater baseline
incidence (Kamez); overall disease control seems to be good.
PMID- 25115472
TI - [Hospitalization study on a cohort of families applying for tenement houses in
Florence (Tuscany Region, Central Italy)].
AB - OBJECTIVES AND DESIGN: to evaluate the morbidity of a materially deprived
population of family members applying for public tenement houses in Florence,
Central Italy, in the period 1977-2001. SETTING AND PARTICIPANTS: all yearly
first hospital admissions concerning 4,773 persons resident in Florence who
applied for tenement houses to local public bodies during 1997-2001 were
collected. MAIN OUTCOME MEASURES: gender specific age-standardized
hospitalization ratios (SHR) for all causes and cause-specific hospital
admissions during 2001- 2005. The expected cases were calculated using as
reference gender, age and cause specific hospitalization rates of Tuscany
population for the 2001-2005 period. RESULTS: 2,777 hospital admissions were
registered. Statistically significant excesses of standardized hospitalization
ratio were observed in both genders for all causes (males: SHR 1.14, 95%CI 1.07
1.20; females: SHR 1.22, 95%CI 1.16-1.28), mental disorders (males: SHR 2.19,
95%CI 1.71- 2.76; females: SHR 1.77, 95%CI 1.35-2.27) and respiratory diseases
(males: SHR 1.25, 95%CI 1.05-1.47; females: SHR 1.33, 95%CI 1.09-1.60). Other
excesses were observed for endocrine, metabolic and immunity disorders only in
males (SHR 1.38, 95%CI 1.04-1.79), and for injuries and poisoning only in females
(SHR 1.24, 95%CI 1.03-1.48). Statistical significant deficits were observed for
neoplasm and for diseases of circulatory system in both genders, and for diseases
of the musculoskeletal system and connective tissue in males. CONCLUSION: the
results, consistent with the available evidences on causes of illness in
disadvantaged groups, point to the importance of built environment and adequate
housing in reducing health inequalities.
PMID- 25115471
TI - [A comparative analysis between regional mesothelioma registries and cancer
registries: results of the ReNaM-AIRTUM project].
AB - OBJECTIVES: to assess the agreement on row data and incidence rates between
regional mesothelioma registries (CORs) and population cancer registries (CRs) in
Italy, and to contribute in harmonizing the procedures used in identifying the
date of incidence and the morphology of mesothelioma cases. SETTING E
PARTICIPANTS: the mesothelioma cases registered by 19 CRs and by 9 out of 19 CORs
were included in the study. Some CORs were not able to participate in the study,
because there were no active CRs in their areas. MAIN OUTCOME MEASURES: agreement
on cases defined as mesotheliomas by the two types of registries; Cohen's k was
used for the evaluation of the agreement on morphology on specific mesothelioma
(ICD-O-3 90513-90533) and mesothelioma not otherwise specified (NOS) (ICD-O-3
90503); instead, Odds Ratio was calculated to evaluate the direction of the
discrepancy. Difference among incidence rates were calculated using data
collected by the two types of registries. It was also made a comparison between
dates of incidence. RESULTS: the comparison among the registered data by the two
different types of registry showed a high concordance (>80%), especially in the
areas where there is a continuous exchange of data. Only in a few areas a lower
concordance was observed. The agreement between specific and non-specific
morphology showed a fairly wide range and lower values than the calculation of
the positive agreement. CORs used the specific morphology (ICD-O-3 90503-90533)
with higher frequency compared to CRs. The CRs incidence standardized rates are
higher when only cases defined as "certain " by ReNaM are considered; on the
opposite the CORs rates are higher when all cases defined as "certain, probable
and possible" are considered. CONCLUSIONS: the study permitted to compare and
bring out the different procedures used in identifying the date of incidence of
cases and morphology definition. This represents a first step of a cooperative
discussion process among the involved registries: the working group hope it will
end with the implementation of shared guidelines.
PMID- 25115473
TI - [Occupational injury risk in immigrant workers in Italy: differences in work
characteristics and age].
AB - OBJECTIVES: to describe occupational injury risk, comparing regular foreign
workers with Italians, by main work characteristics and age. DESIGN: analysis of
incidence and risk of total and severe occupational injury by Country of birth,
stratified by economic activity, skill level, geographical area of work, firm
size and age. SETTING AND PARTICIPANTS: sample of 7% of workers registered in the
Italian National Institute of Social Insurance (INPS) database. The workers
considered were male private sector employees aged from 16 to 55 years old who
worked between 2000 and 2005 as apprentice or blue collar. Two groups were
distinguished: immigrants from high migratory pressure Countries (PFPM) and
immigrants from high-income Countries (PSA; Italians comprised). The three main
nationalities considered were the most relevant in Italy: Moroccans, Albanians,
and Romanians. MAIN OUTCOME MEASURES: all occupational injuries; severe
occupational injuries based on the type of damage. RESULTS AND CONCLUSIONS: PFPM
workers have a higher risk of injury compared to PSA both for total (Relative
Risk - RR: 1.45) and severe ones (RR: 1.56), particularly in engineering (RR:
1.64) and trade (RR: 1.61). Moroccans have always the greatest risks (RR: 1.86);
Romanians are protected on total injuries (RR: 0.80), but have excess of risk of
severe injuries (RR: 1.31). Among young people there aren't differences by
Country of birth, but the rate decreases as age increases in PSA, while in PFPM
it increases as age increases. In this study, injury risk in regular foreign
workers were measured more accurately than official statistics: Whip-Salute
database can provide useful information for planning prevention programmes of
immigrant work-related injuries.
PMID- 25115474
TI - [Updating of the prevalence of congenital anomalies among resident births in the
Municipality of Gela (Southern Italy)].
AB - OBJECTIVES: to update the prevalence of congenital anomalies in the Municipality
of Gela (Southern Italy), in particular to verify whether the previously reported
high prevalence of hypospadias was confirmed. DESIGN: study on prevalence at
birth of congenital anomalies by retrieving information from multiple sources.
SETTING AND PARTICIPANTS: in the Municipality of Gela it is localized a site of
national interest for environmental remediation (SIN). Data of residents born in
the Municipality of Gela in 2003-2008 were recovered from hospital records, local
and regional archives, Sicilian registry of congenital malformations database,
hospital admissions at medical and surgical hospitals in Catania. For comparison,
European (EUROCAT), Tuscany and Emilia-Romagna registries data have been used.
MAIN OUTCOME MEASURES: congenital anomalies, divided into confirmed anomalies,
minor anomalies, uncertain conditions, classified by large groups and specific
anomalies. RESULTS: statistically significant excesses emerge with respect to the
references for genital anomalies, and for urinary and total anomalies including
not-specified diagnoses. For cardiovascular and limb anomalies (including not
specified clubfoot), the excess is significant only in comparison with Italian
figures. The prevalence of hypospadias of 46.7/10,000 shows statistically
significant excesses compared to European and Italian reference values, of 1.7
and 2.3 times, respectively. CONCLUSION: retrospective recovery of data produced
incompleteness of cases and poor diagnostic definition. The epidemiological
picture is more reliable for congenital anomalies less susceptible to termination
of pregnancy. The study confirms a high prevalence of hypospadias, estimated
between the value observed in the previous twelve-year study and the one reported
for the area of Priolo-Augusta-Melilli for the years 1990-1998; and higher than
those reported in literature, with sporadic exceptions. The observed data, as
well as the documented presence in the environment and in biological fluids of
dangerous pollutants in periconceptional exposures, support a plausibility of
multifactorial aetiology for hypospadias. The environmental risk should not be
neglected in the decisions of primary prevention.
PMID- 25115476
TI - [Airport related air pollution and health effects].
AB - Airport is an extremely complex emission source of airborne pollutants that can
have a significant impact on the environment. Indeed, several airborne chemicals
emitted during airport activities may significantly get worse air quality and
increase exposure level of both airport workers and general population living
nearby the airports. In recent years airport traffic has increased and
consequently several studies investigated the association between airport-related
air pollution and occurrence of adverse health effects, particularly on
respiratory system, in exposed workers and general population resident nearby. In
this context, we carried out a critical evaluation of the studies that
investigated this correlation in order to obtain a deeper knowledge of this issue
and to identify the future research needs. Results show that the evidence of
association between airport-related air pollution and health effects on workers
and residents is still limited.
PMID- 25115477
TI - [Air pollution in an urban area nearby the Rome-Ciampino city airport].
AB - OBJECTIVES: to assess air pollution spatial and temporal variability in the urban
area nearby the Ciampino International Airport (Rome) and to investigate the
airport-related emissions contribute. DESIGN AND SETTING: the study domain was a
64 km2 area around the airport. Two fifteen-day monitoring campaigns (late
spring, winter) were carried out. Results were evaluated using several runs
outputs of an airport-related sources Lagrangian particle model and a
photochemical model (the Flexible Air quality Regional Model, FARM). MAIN OUTCOME
MEASURES: both standard and high time resolution air pollutant concentrations
measurements: CO, NO, NO2, C6H6, mass and number concentration of several PM
fractions. 46 fixed points (spread over the study area) of NO2 and volatile
organic compounds concentrations (fifteen days averages); deterministic models
outputs. RESULTS: standard time resolution measurements, as well as model
outputs, showed the airport contribution to air pollution levels being little
compared to the main source in the area (i.e. vehicular traffic). However, using
high time resolution measurements, peaks of particles associated with aircraft
takeoff (total number concentration and soot mass concentration), and landing
(coarse mass concentration) were observed, when the site measurement was downwind
to the runway. CONCLUSIONS: the frequently observed transient spikes associated
with aircraft movements could lead to a not negligible contribute to ultrafine,
soot and coarse particles exposure of people living around the airport. Such
contribute and its spatial and temporal variability should be investigated when
assessing the airports air quality impact.
PMID- 25115478
TI - [Airports and air quality: a critical synthesis of the literature].
AB - This work reviewed existing literature on airport related activities that could
worsen surrounding air quality; its aim is to underline the progress coming from
recent-year studies, the knowledge emerging from new approaches, the development
of semi-empiric analytical methods as well as the questions still needing to be
clarified. To estimate pollution levels, spatial and temporal variability, and
the sources relative contributions integrated assessment, using both fixed point
measurement and model outputs, are needed. The general picture emerging from the
studies was a non-negligible and highly spatially variable (within 2-3 km from
the fence line) airport contribution; even if it is often not dominant compared
to other concomitant pollution sources. Results were highly airport-specific.
Traffic volumes, landscape and meteorology were the key variables that drove the
impacts. Results were thus hardly exportable to other contexts. Airport related
pollutant sources were found to be characterized by unusual emission patterns
(particularly ultrafine particles, black carbon and nitrogen oxides during take
off); high time-resolution measurements allow to depict the rapidly changing take
off effect on air quality that could not be adequately observed otherwise. Few
studies used high time resolution data in a successful way as statistical models
inputs to estimate the aircraft take-off contribution to the observed average
levels. These findings should not be neglected when exposure of people living
near airports is to be assessed.
PMID- 25115479
TI - [Arsenic contamination in Italy: a comment on the SEpiAs study].
PMID- 25115475
TI - [Health impact assessment of airport noise on people living nearby six Italian
airports].
AB - BACKGROUND: aircraft noise has been associated with several health effects.
Because of the great success of low-cost flights, small airports have been turned
into international airports thus exposing nearby residents to an increase in
noise levels and potential disturbances and health disorders. OBJECTIVE: to
estimate the exposure levels and evaluate the health impact of aircraft noise on
residents nearby six airports in Italy (Rome: Ciampino; Milan: Linate and
Malpensa; Pisa; Turin; Venice) focusing on hypertension, acute myocardial
infarction (AMI), annoyance and sleep disturbances. METHODS: residents in the
local Municipalities considered at 31.12.2010 were included in the study and
their addresses were geocoded. Aircraft noise exposure in 2011 was defined using
the Integrated Noise Model linked to each participant's address. Lden (<55, 55
60, 61-65, 65-70 dB), Lnight, Leq (day and night) were calculated. Available
exposure-response relationships were used to estimate the number of additional
cases of hypertension, AMI, annoyance and sleep disturbances in the local
population. RESULTS: 73,272 persons exposed to aircraft noise levels >55dB were
considered: 55,915 (76.3%) were exposed to 55-60 dB; 16,562 (22.6%) to 60-65 dB;
795 (1.2%) to 65-70 dB. Exposure to aircraft noise levels above 55 dB was
estimated to be responsible each year of 4,607 (95%CI 0-9,923) additional cases
of hypertension; 3.4 (95%CI 0-10.7) cases of AMI; 9,789 (95%CI 6,895-11,962)
cases of annoyance; 5,084 (95%CI 1,894-10,509) cases of sleep disturbances.
CONCLUSIONS: a significant impact of airport noise on the health of residents
nearby six Italian airports was estimated. Epidemiological evaluation and noise
mitigation measures should be introduced to protect the health of residents.
PMID- 25115480
TI - [Vaping: a new strategy to prevent smoking-related diseases?].
AB - By quitting, smokers of all ages can gain substantial health benefits. No other
single effort of public health is able to achieve an advantage comparable to
smoking cessation on a large scale. However, conventional approaches to smoking
cessation require tobacco users to completely abstain, and many smokers are
unable - or have not the willingness - to achieve this goal, and then continue to
smoke despite the looming negative consequences for health. But it is possible to
consider another option: the reduction of harm caused by tobacco smoking (tobacco
harm reduction) through the intake of nicotine from alternative sources safer
than tobacco smoke, such as the electronic cigarette (e-cig). It is a promising
product for the reduction of harm caused by tobacco smoking. In addition to
providing nicotine through the vapour without the typical toxic and carcinogenic
substances derived from combustion, the e-cig is also a good substitute for the
rituals associated with the behaviour of the smoker. In this article, the author
suggests that the wide dissemination of vaping behaviour can become a successful
strategy to reduce smoking and preventing smoking-related diseases, advancing on
how to succeed with this matter.
PMID- 25115481
TI - [Codes, guidelines and guidance of ethics of research: the issue of quality].
AB - After an overview of the evolution of ethics laws for medical activities, we
suggest a possible classification of documents regarding the ethical conduct of
scientific research with human beings. The authors outline the necessity to
define formal criteria for the development and the implementation of ethics
standards.
PMID- 25115483
TI - [In Italy, prevalence of smokers and manufactured cigarettes sales are
decreasing, but social differences and sales of fine-cut tobacco are increasing].
PMID- 25115482
TI - [In 2014 cancer registration covers more than half of the Italian population].
PMID- 25115484
TI - Salt-induced self-assembly of bacteria on nanowire arrays.
AB - Studying bacteria-nanostructure interactions is crucial to gaining controllable
interfacing of biotic and abiotic components in advanced biotechnologies. For
bioelectrochemical systems, tunable cell-electrode architectures offer a path
toward improving performance and discovering emergent properties. As such,
Sporomusa ovata cells cultured on vertical silicon nanowire arrays formed
filamentous cells and aligned parallel to the nanowires when grown in increasing
ionic concentrations. Here, we propose a model describing the kinetic and the
thermodynamic driving forces of bacteria-nanowire interactions.
PMID- 25115485
TI - Protection of Wistar-Furth rats against postischaemic acute renal injury: role
for nitric oxide and thromboxane?
AB - The Wistar-Furth (WF) rat strain is usually used in models of full major
histocompatibility complex-mismatched kidney transplantation. Because these rats
have been demonstrated to be resistant to several models of chronic kidney
disease, the aim of the present study was to investigate their potential
resistance to renal ischaemia-reperfusion (I/R) injury compared with another
strain, namely Wistar-Hanover (WH) rats. Anaesthetized male WH and WF rats were
submitted to I/R by occlusion of the left renal artery and contralateral
nephrectomy. Urine, blood and tissue samples were collected at different time
points after I/R to evaluate renal function, inflammation and tubular injury,
along with determination of nitric oxide synthase (NOS) expression and
thromboxane A2 (TxA2 ) production. Post-ischaemic renal function was better
preserved in WF than WH rats, as evidenced by reduced levels of creatininaemia,
urinary neutrophil gelatinase-associated lipocalin excretion and proteinuria. In
addition, WF rats had less intrarenal inflammation than WH rats after I/R injury.
These observations were associated with maintenance of neuronal NOS expression,
along with lower induction of inducible NOS expression in WF versus WH rats.
Moreover, WF rats excreted a significantly lower amount of TxB2 . The results
indicate that WF rats are more resistant to an I/R injury than WH rats in terms
of renal function and inflammation. These observations are associated with
differential regulation of intrarenal NOS expression, as well as a reduction in
thromboxane production, which could contribute to a better outcome for the
postischaemic kidney in WF rats.
PMID- 25115486
TI - X-linked adrenoleukodystrophy: pathogenesis and treatment.
AB - X-linked adrenoleukodystrophy (X-ALD) is a puzzling inborn error of metabolism
with a strikingly heterogeneous clinical spectrum. All patients have mutations in
the ABCD1 gene and accumulate very long chain fatty acids in all tissues.
Virtually all male X-ALD patients develop adrenocortical insufficiency in
childhood and progressive myelopathy and peripheral neuropathy in adulthood. A
subset of male patients, however, develops a fatal cerebral demyelinating
disease, cerebral adrenoleukodystrophy. Female patients also develop progressive
myelopathy and peripheral neuropathy, but generally at a later age than males.
They only very rarely develop adrenocortical insufficiency or cerebral
adrenoleukodystrophy. This review proposes to simplify the classification of the
clinical spectrum of X-ALD and reviews the largely unresolved pathophysiological
mechanisms and the current treatment options.
PMID- 25115487
TI - Traffic jam in the primitive streak: the role of defective mesoderm migration in
birth defects.
AB - Gastrulation is the process in which the three germ layers are formed that
contribute to the formation of all major tissues in the developing embryo. We
here review mouse genetic models in which defective gastrulation leads to
mesoderm insufficiencies in the embryo. Depending on severity of the
abnormalities, the outcomes range from incompatible with embryonic survival to
structural birth defects, such as heart defects, spina bifida, or caudal
dysgenesis. The combined evidence from the mutant models supports the notion that
these congenital anomalies can originate from perturbations of mesoderm
specification, epithelial-mesenchymal transition, and mesodermal cell migration.
Knowledge about the molecular pathways involved may help to improve strategies
for the prevention of major structural birth defects.
PMID- 25115489
TI - A systematic review of evaluated suicide prevention programs targeting indigenous
youth.
AB - BACKGROUND: Indigenous young people have significantly higher suicide rates than
their non-indigenous counterparts. There is a need for culturally appropriate and
effective suicide prevention programs for this demographic. AIMS: This review
assesses suicide prevention programs that have been evaluated for indigenous
youth in Australia, Canada, New Zealand, and the United States. METHOD: The
databases MEDLINE and PsycINFO were searched for publications on suicide
prevention programs targeting indigenous youth that include reports on
evaluations and outcomes. Program content, indigenous involvement, evaluation
design, program implementation, and outcomes were assessed for each article.
RESULTS: The search yielded 229 articles; 90 abstracts were assessed, and 11
articles describing nine programs were reviewed. Two Australian programs and
seven American programs were included. Programs were culturally tailored,
flexible, and incorporated multiple-levels of prevention. No randomized
controlled trials were found, and many programs employed ad hoc evaluations, poor
program description, and no process evaluation. CONCLUSION: Despite culturally
appropriate content, the results of the review indicate that more controlled
study designs using planned evaluations and valid outcome measures are needed in
research on indigenous youth suicide prevention. Such changes may positively
influence the future of research on indigenous youth suicide prevention as the
outcomes and efficacy will be more reliable.
PMID- 25115491
TI - Suicide ideation and attempts and bullying in children and adolescents:
psychiatric and general population samples.
AB - BACKGROUND: Studies of the relationship between bullying and suicide behavior
yield mixed results. AIMS: This is the first study comparing frequencies of
suicide behavior in four bullying groups (bully, victim, bully/victim, and
neither) in two large psychiatric and community samples of young children and
adolescents. METHOD: Maternal ratings of bullying and suicide ideation and
attempts were analyzed for 1,291 children with psychiatric disorders and 658
children in the general population 6-18 years old. RESULTS: For both the
psychiatric and community samples, suicide ideation and attempt scores for
bully/victims were significantly higher than for victims only and for neither
bullies nor victims. Differences between victims only and neither victims nor
bullies were nonsignificant. Controlling for sadness and conduct problems,
suicide behavior did not differ between the four bullying groups. All children
with suicide attempts had a comorbid psychiatric disorder, as did all but two
children with suicide ideation. CONCLUSION: Although the contribution of bullying
per se to suicide behavior independent of sadness and conduct problems is small,
bullying has obvious negative psychological consequences that make intervention
imperative. Interventions need to focus on the psychopathology associated with
being a victim and/or perpetrator of bullying in order to reduce suicide
behavior.
PMID- 25115490
TI - Assessing suicide attempts and depression among Chinese speakers over the
Internet.
AB - BACKGROUND: In populations where mental health resources are scarce or
unavailable, or where stigma prevents help-seeking, the Internet may be a way to
identify and reach at-risk persons using self-report validated screening tools as
well as to characterize individuals seeking health information online. AIMS: We
examined the feasibility of delivering an Internet-based Chinese-language
depression and suicide screener and described its users. METHOD: An Internet
based depression and suicide screener was created and advertised primarily
through Google AdWords. Participants completed a suicide and depression screening
measure and received individualized feedback, which, if necessary, included the
suggestion to seek additional mental health resources. RESULTS: In 7 months,
11,631 individuals visited the site; 4,709 provided valid information. Nearly
half reported a current major depressive episode (MDE) and 18.3% a recent suicide
attempt; however, over 75% reported never having sought help, including 77.7% of
those with MDEs and 75.9% of those reporting a suicide attempt. As participants
found the site by searching for depression information online, results may not
generalize to the entire Chinese-speaking population. CONCLUSION: Online
screening can feasibly identify and reach many at-risk Chinese-speaking persons.
It may provide resources to those with limited access to services or to those
reluctant to seek such services.
PMID- 25115488
TI - IglC and PdpA are important for promoting Francisella invasion and intracellular
growth in epithelial cells.
AB - The highly infectious bacteria, Francisella tularensis, colonize a variety of
organs and replicate within both phagocytic as well as non-phagocytic cells, to
cause the disease tularemia. These microbes contain a conserved cluster of
important virulence genes referred to as the Francisella Pathogenicity Island
(FPI). Two of the most characterized FPI genes, iglC and pdpA, play a central
role in bacterial survival and proliferation within phagocytes, but do not
influence bacterial internalization. Yet, their involvement in non-phagocytic
epithelial cell infections remains unexplored. To examine the functions of IglC
and PdpA on bacterial invasion and replication during epithelial cell infections,
we infected liver and lung epithelial cells with F. novicida and F. tularensis
'Type B' Live Vaccine Strain (LVS) deletion mutants (DeltaiglC and DeltapdpA) as
well as their respective gene complements. We found that deletion of either gene
significantly reduced their ability to invade and replicate in epithelial cells.
Gene complementation of iglC and pdpA partially rescued bacterial invasion and
intracellular growth. Additionally, substantial LAMP1-association with both
deletion mutants was observed up to 12 h suggesting that the absence of IglC and
PdpA caused deficiencies in their ability to dissociate from LAMP1-positive
Francisella Containing Vacuoles (FCVs). This work provides the first evidence
that IglC and PdpA are important pathogenic factors for invasion and
intracellular growth of Francisella in epithelial cells, and further highlights
the discrete mechanisms involved in Francisella infections between phagocytic and
non-phagocytic cells.
PMID- 25115494
TI - Effect of a contact monitoring system with immediate visual feedback on hand
hygiene compliance.
AB - BACKGROUND: Hand hygiene compliance is traditionally monitored by visual methods
that are open to bias and strictly limited in time and place. Automatic
monitoring may be more effective for infection control as well as performance
management. AIM: To establish accuracy and acceptability of an automatic contact
monitoring system for hand hygiene. METHODS: Monitoring equipment was installed
across 55 beds in three wards, and included modified identity badges, bedside
furniture, sinks and alcohol gel dispensers. Badges were in near-skin contact
(through uniform) and could detect alcohol vapour. All devices were linked by wi
fi. A traffic light system on the badge provided immediate feedback to staff and
patients on the hand hygiene status of a member of staff on approach to a
patient. Compliance was logged automatically. Following a period of immediate
feedback, no visual feedback was given for two weeks. Subsequently, feedback was
given using red/green lights for 10 days, followed by retrospective feedback to
the ward. Hand hygiene was verified independently by an observer. FINDINGS: Hand
hygiene compliance increased from 21% of 97 opportunities to 66% of 197
opportunities during active immediate feedback. Compliance decreased when
feedback was provided to wards retrospectively. Six staff (26%) avoided wearing a
badge, saying that it was too heavy or they were not on the ward all day. Only
three of 30 patients stated that they would challenge staff who had not performed
hand hygiene. CONCLUSIONS: Automatic contact monitoring with immediate feedback
was effective in increasing hand hygiene compliance, but feedback given
retrospectively did not prevent a decrease in compliance.
PMID- 25115496
TI - Urinoma following Kidney Biopsy: A Case Report.
AB - Major complications of a percutaneous kidney biopsy are infrequent but warrant
early detection and appropriate treatment. We herein report a patient who
developed urinoma following kidney biopsy in the effort to emphasize the
paramount importance for practitioners to recognize this complication. Prompt
diagnosis and proper management of urinoma following kidney biopsy is prudent as
delayed treatment may lead to abscess formation, hydronephrosis, obstructive
uropathy and chronic kidney failure.
PMID- 25115493
TI - Cross-immunity and age patterns of influenza A(H5N1) infection.
AB - The age distribution of influenza A(H5N1) cases reported during 2006-2013 varied
substantially between countries. As well as underlying demographic profiles, it
is possible that cross-immunity contributed to the age distribution of reported
cases: seasonal influenza A(H1N1) and avian influenza A(H5N1) share the same
neuraminidase subtype, N1. Using a mechanistic model, we measured the extent to
which population age distribution and heterosubtypic cross-immunity could explain
the observed age patterns in Cambodia, China, Egypt, Indonesia and Vietnam. Our
results support experimental evidence that prior infection with H1N1 confers
partial cross-immunity to H5N1, and suggest that more than 50% of spillover
events did not lead to reported cases of infection as a result. We also
identified age groups that have additional risk factors for influenza A(H5N1) not
captured by demography or infection history.
PMID- 25115497
TI - Characterization of a double-hit murine model of acute respiratory distress
syndrome.
AB - The aim of the present study was to characterize a murine model of acute
respiratory distress syndrome (ARDS) abiding by the Berlin definition of human
ARDS and guidelines for animal models of ARDS. To this end, C57BL/6NCrl mice were
challenged with lipopolysaccharide (LPS; 15 mg/kg, i.p.) followed 18 h later by
injection of oleic acid (OA; 0.12 mL/kg, i.v.). Controls received saline
injection at both time points. Haemodynamics were monitored continuously.
Arterial blood gas analyses were performed just before and every 30 min after OA
challenge. Ninety minutes after OA challenge, the chest of mice was scanned using
micro-computed tomography (CT). Cytokine concentrations were measured in plasma
samples. Lungs were harvested 90 min after OA challenge for histology,
immunohistochemistry, lung weight measurements and tissue cytokine detection. A
histological lung injury score was determined. Eighteen hours after LPS
challenge, mice exhibited a severe systemic inflammatory response syndrome.
Oxygenation declined significantly after OA injections (Pa o2 /Fi o2 283 +/- 73
and 256 +/- 71 mmHg at 60 and 90 min, respectively; P < 0.001). Bilateral patchy
infiltrates were present on the micro-CT scans. Histology revealed parenchymal
damage with accumulation of polymorphonuclear neutrophils, intra-alveolar
proteinacous debris and few hyaline membranes. The lung wet : dry ratio indicated
damage to the alveolar capillary membrane. Cytokine patterns evidenced a severe
local and systemic inflammatory state in plasma and lung tissue. In conclusion,
the described two-hit model of ARDS shows a pathological picture of ARDS closely
mimicking human ARDS according to the Berlin definition and may facilitate
interpretation of prospective experimental results.
PMID- 25115498
TI - A MAVS/TICAM-1-independent interferon-inducing pathway contributes to regulation
of hepatitis B virus replication in the mouse hydrodynamic injection model.
AB - Toll-like receptors (TLRs) and cytoplasmic RNA sensors have been reported to be
involved in the regulation of hepatitis B virus (HBV) replication, but remain
controversial due to the lack of a natural infectious model. Our current study
sets out to characterize aspects of the role of the innate immune system in
eliminating HBV using hydrodynamic-based injection of HBV replicative plasmid and
knockout mice deficient in specific pathways of the innate system. The evidence
indicated that viral replication was not affected by MAVS or TICAM-1 knockout,
but absence of interferon regulatory factor 3 (IRF-3) and IRF-7 transcription
factors, as well as the interferon (IFN) receptor, had an adverse effect on the
inhibition of HBV replication, demonstrating the dispensability of MAVS and TICAM
1 pathways in the early innate response against HBV. Myd88(-/-) mice did not have
a significant increase in the initial viremia, but substantial viral antigen
persisted in the mice sera, a response similar to Rag2(-/-) mice, suggesting that
the MyD88-dependent pathway participated in evoking an adaptive immune response
against the clearance of intrahepatic HBV. Taken together, we show that the RNA
sensing pathways do not participate in the regulation of HBV replication in a
mouse model; meanwhile MyD88 is implicated in the HBV clearance.
PMID- 25115499
TI - Endoscopic approaches for the diagnosis of autoimmune pancreatitis.
AB - Autoimmune pancreatitis (AIP) is characterized by diffuse pancreatic enlargement
and irregular narrowing of the main pancreatic duct (MPD). Immunoglobulin (Ig)G4
related sclerosing cholangitis (IgG4-SC) associated with AIP frequently appears
as a bile duct stricture. Therefore, it is important to differentiate AIP and
IgG4-SC from pancreatic cancer and cholangiocarcinoma or primary sclerosing
cholangitis, respectively. Endoscopy plays a central role in the diagnosis of AIP
and IgG4-SC because it provides imaging of the MPD and bile duct strictures as
well as the ability to obtain tissue samples for histological evaluations.
Diffuse irregular narrowing of MPD on endoscopic retrograde
cholangiopancreatography (ERCP) is rather specific to AIP, but localized
narrowing of the MPD is often difficult to differentiate from MPD stenosis caused
by pancreatic cancer. A long stricture (>1/3 the length of the MPD) and lack of
upstream dilatation from the stricture (<5 mm) might be key features of AIP on
ERCP. Some cholangiographic features, such as segmental strictures, stric tures
of the lower bile duct, and long strictures with prestenotic dilatation, are more
common in IgG4-SC than in cholangiocarcinoma. Endoscopic ultrasonography (EUS)
reveals diffuse hypoechoic pancreatic enlargement, sometimes with hypoechoic
inclusions, in patients with AIP. In addition, EUS-elastography and contrast
enhanced harmonic EUS have been developed with promising results. The usefulness
of EUS-guided fine-needle aspiration has been increasingly recognized for
obtaining adequate tissue samples for the histological diagnosis of AIP. Further
improvement of endoscopic procedures and devices will contribute to more accurate
diagnosis of AIP and IgG4-SC.
PMID- 25115500
TI - Vitamin D deficiency in patients with primary immune-mediated peripheral
neuropathies.
AB - PURPOSE: T cells are important in the immunopathology of immune-mediated
peripheral neuropathies (PNP) and activated vitamin D regulates the immune
response through increasing the amount of regulatory T cells. An association
between vitamin D deficiency and polyneuropathy has been stipulated; hence we
assessed whether patients with primary immune-mediated PNP have low vitamin D
[25(OH)D] levels. METHODS: Plasma levels of 25(OH)D were analyzed in 26 patients
with primary immune-mediated PNP, 50 healthy matched blood donors and 24 patients
with motor neuron disease (MND). INCAT score was assessed in patients with
Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy.
ALSFRS-R score was applied to MND patients and the modified Rankin (mRankin)
scale compared disability among patient groups. RESULTS: Mean 25(OH)D value in
PNP patients was 40 +/- 16 nmol/l, compared to 69 +/- 21 nmol/l in healthy blood
donors (p<0.001). MND patients had a higher mean 25(OH)D than PNP patients (59 +/
26 nmol/L; p=0.006) and comparable levels to healthy blood donors (p=0.15). Mean
25(OH)D value was not higher in PNP patients with pre-existing vitamin D3
supplementation of 800 IU/day (N=6; 35 +/- 18 nmol/L) than in unsupplemented PNP
patients (42 +/- 16 nmol). INCAT score ranged from 0 to 10 (mean 3.5) and ALSFRS
R ranged from 11 to 44 (mean 31). mRankin score was more severe in MND patients
(mean 3.5) compared to PNP patients (mean 2.1). CONCLUSIONS: All patients with
primary immune-mediated PNP were diagnosed with vitamin D deficiency and they had
significantly lower 25(OH)D values than healthy control persons and MND patients.
We suggest monitoring of vitamin D status in patients with autoimmune PNP, since
immune cells are responsive to the ameliorative effects of vitamin D.
PMID- 25115501
TI - Acute neurological worsening after Rituximab treatment in patients with anti-MAG
neuropathy.
AB - BACKGROUND: Patients with peripheral neuropathy and anti-MAG monoclonal IgM may
respond to Rituximab, a humanized monoclonal anti-CD20 antibody. METHODS: We
report on three patients with peripheral neuropathy and anti-MAG monoclonal IgM
who deteriorated under Rituximab and reviewed seven previously published cases.
RESULTS: Worsening was acute and severe, and occurred during the treatment
period. All the patients improved after deterioration but at final evaluation
only one was improved comparatively to baseline, five were worsened and four were
stabilized. Deterioration was not clearly associated with an increase of the anti
MAG antibody titer. Two patients received Rituximab prior or after the course
which induced worsening without adverse reaction. CONCLUSION: Although rare,
acute worsening of the neuropathy can occur after Rituximab. The deterioration is
however reversible within some weeks to several months.
PMID- 25115502
TI - Are natural killer cells involved in multiple sclerosis etiology? Evidences from
NKp46/NCR1 receptor modulation in an observational study.
AB - Natural killer (NK) cells are implicated in many autoimmune diseases but their
role in multiple sclerosis (MS) remains still unknown. This study was aimed to
evaluate the expression levels of a NK cell receptor (NCR1) in patients with
diagnosis of MS. Particularly, the study took into account patients undergoing
pharmacological therapy with interferon-beta or natalizumab and patients never
treated since first-time diagnosed for MS. Expression levels of NCR1 receptor
were evaluated in protein extracts of peripheral blood mononuclear cells
performing western blot analysis. Our results show that MS patients display
higher NCR1 expression levels than healthy controls. Moreover, patients with a
first diagnosis of MS display the highest level of NCR1 when compared with
patients pharmacologically treated with interferon-beta or natalizumab.
Therefore, pharmacologically treated MS patients show a modulated NK cell
expression.
PMID- 25115503
TI - Sporadic Creutzfeldt-Jakob disease with mesiotemporal hypermetabolism.
PMID- 25115505
TI - G tolerance and the vasoconstrictor reserve.
AB - PURPOSE: Because leg arterial stiffness is higher in subjects with high G
tolerance, we hypothesized that subjects with high G tolerance would have larger
capacity for vasoconstriction. METHODS: Sixteen subjects, eight with high and
eight with low G tolerance (H and L group, respectively), were exposed to a cold
pressor test (CPT) in supine and upright posture. Heart rate (HR), mean arterial
pressure (MAP) and cardiac output (CO) were measured, and total peripheral
resistance (TPR) and stroke volume (SV) were calculated. RESULTS: In the supine
position, CPT increased TPR more in the H group; 31 +/- 18% than in the L group;
11 +/- 7% (p < 0.05). The L group had larger increases in CO than the H group; 17
+/- 16 vs. 3.4 +/- 7% (p = 0.06). In the upright position, the H group had a
larger MAP response to CPT than the L group; 26 +/- 14 vs. 14 +/- 7% (p = 0.06).
The H group, but not the L group, had significant increases in TPR whereas the L
group had significant increases in CO and SV. CONCLUSIONS: In response to CPT,
the high G tolerance group elevated MAP by increasing TPR, whereas the low G
tolerance group showed a dependency on increased CO. The H group seemed to have a
larger vasoconstrictor reserve. The results further suggest that vasoconstrictor
reserve capacity could constitute the link between the recent finding that
indicates a relationship between G tolerance and arterial distensibility in the
legs.
PMID- 25115504
TI - Analysis of the quantitative balance between insulin-like growth factor (IGF)-1
ligand, receptor, and binding protein levels to predict cell sensitivity and
therapeutic efficacy.
AB - BACKGROUND: The insulin-like growth factor (IGF) system impacts cell
proliferation and is highly activated in ovarian cancer. While an attractive
therapeutic target, the IGF system is complex with two receptors (IGF1R, IGF2R),
two ligands (IGF1, IGF2), and at least six high affinity IGF-binding proteins
(IGFBPs) that regulate the bioavailability of IGF ligands. We hypothesized that a
quantitative balance between these different network components regulated cell
response. RESULTS: OVCAR5, an immortalized ovarian cancer cell line, were found
to be sensitive to IGF1, with the dose of IGF1 (i.e., the total mass of IGF1
available) a more reliable predictor of cell response than ligand concentration.
The applied dose of IGF1 was depleted by both cell-secreted IGFBPs and endocytic
trafficking, with IGFBPs sequestering up to 90% of the available ligand. To
explore how different variables (i.e., IGF1, IGFBPs, and IGF1R levels) impacted
cell response, a mass-action steady-state model was developed. Examination of the
model revealed that the level of IGF1-IGF1R complexes per cell was directly
proportional to the extent of proliferation induced by IGF1. Model analysis
suggested, and experimental results confirmed, that IGFBPs present during IGF1
treatment significantly decreased IGF1-mediated proliferation. We utilized this
model to assess the efficacy of IGF1 and IGF1R antibodies against different
network compositions and determined that IGF1R antibodies were more globally
effective due to the receptor-limited state of the network. CONCLUSIONS: Changes
that affect IGF1R occupancy have predictable effects on IGF1-induced
proliferation and our model captured these effects. Analysis of this model
suggests that IGF1R antibodies will be more effective than IGF1 antibodies,
although the difference was minimal in conditions with low levels of IGF1 and
IGFBPs. Examining how different components of the IGF system influence cell
response will be critical to improve our understanding of the IGF signaling
network in ovarian cancer.
PMID- 25115506
TI - Assessing neonatal heat balance and physiological strain in newborn infants
nursed under radiant warmers in intensive care with fentanyl sedation.
AB - PURPOSE: To assess heat balance status of newborn infants nursed under radiant
warmers (RWs) during intensive care. METHODS: Heat balance, thermal status and
primary indicators of physiological strain were concurrently measured in 14
newborns nursed under RWs for 105 min. Metabolic heat production (M), evaporative
heat loss (E), convective (C) and conductive heat flow (K), rectal temperature (T
re) and mean skin temperatures (T sk) were measured continuously. The rate of
radiant heat required for heat balance (R req) and the rate of radiant heat
provided (R prov) were derived. The rate of body heat storage (S) was calculated
using a two-compartment model of 'core' (T re) and 'shell' (T sk) temperatures.
RESULTS: Mean M, E, C and K were 10.5 +/- 2.7 W, 5.8 +/- 1.1 W, 6.2 +/- 0.8 W and
0.1 +/- 0.1 W, respectively. Mean R prov (1.7 +/- 2.6 W) and R req (1.7 +/- 2.7
W) were similar (p > 0.05). However, while the resultant mean change in body heat
content after 105 min was negligible (-0.1 +/- 3.7 kJ), acute time-dependent
changes in S were evidenced by a mean positive heat storage component of +6.4 +/-
2.6 kJ and a mean negative heat storage component of -6.5 +/- 3.7 kJ.
Accordingly, large fluctuations in both T re and T sk occurred that were actively
induced by changes in RW output. Nonetheless, no active physiological responses
(heart rate, breathing frequency and mean arterial pressure) to these bouts of
heating and cooling were observed. CONCLUSIONS: RWs maintain net heat balance
over a prolonged period, but actively induce acute bouts of heat imbalance that
cause rapid changes in T re and T sk. Transient bouts of heat storage do not
exacerbate physiological strain, but could in the longer term.
PMID- 25115508
TI - Late reactivation of occult hepatitis B virus infection in a patient with chronic
lymphocytic leukemia after rituximab and fludarabine-based regimen.
PMID- 25115507
TI - Combined caffeine and carbohydrate ingestion: effects on nocturnal sleep and
exercise performance in athletes.
AB - PURPOSE: In athletes, caffeine use is common although its effects on sleep have
not been widely studied. This randomised, double-blind, placebo-controlled
crossover trial investigated the effects of late-afternoon caffeine and
carbohydrate-electrolyte (CEB) co-ingestion on cycling performance and nocturnal
sleep. METHODS: Six male cyclists/triathletes (age 27.5 +/- 6.9 years) completed
an afternoon training session (TS; cycling 80 min; 65% VO2max) followed by a 5 kJ
kg(-1) cycling time trial (TT). Caffeine (split dose 2 * 3 mg kg(-1)) or placebo
was administered 1 h prior and 40 min into the TS. A 7.4% CEB (3 ml kg(-1) every
15 min) was administered during the TS, followed 30 min after by a standardised
evening meal. Participants retired at their usual bedtime and indices of sleep
duration and quality were monitored via polysomnography. DATA: mean +/- SD.
RESULTS: All participants performed better in the caffeine TT (caffeine 19.7 +/-
3.3; placebo 20.5 +/- 3.5 min; p = 0.006), while ratings of perceived exertion
(caffeine 12.0 +/- 0.6; placebo 12.9 +/- 0.7; p = 0.004) and heart rate (caffeine
175 +/- 6; placebo 167 +/- 11 bpm; p = 0.085) were lower in the caffeine TS.
Caffeine intake induced significant disruptions to a number of sleep indices
including increased sleep onset latency (caffeine 51.1 +/- 34.7; placebo 10.2 +/-
4.2 min; p = 0.028) and decreased sleep efficiency (caffeine 76.1 +/- 19.6;
placebo 91.5 +/- 4.2%; p = 0.028), rapid eye movement sleep (caffeine 62.1 +/-
19.6; placebo 85.8 +/- 24.7 min; p = 0.028) and total sleep time (caffeine 391 +/
97; placebo 464 +/- 49 min; p = 0.028). CONCLUSIONS: This study supports a
performance-enhancing effect of caffeine, although athletes (especially those
using caffeine for late-afternoon/evening training and competition) should
consider its deleterious effects on sleep.
PMID- 25115509
TI - Comparison of different DNA extraction methods from peripheral blood cells:
advice from the Fondazione Italiana Linfomi Minimal Residual Disease Network.
AB - Genomic DNA extraction is a primary component of genomic research and diagnostic
routine analysis. Recently, the importance of this process has been highlighted
by the necessity to standardize the diagnostic procedure. In this regard, the
Minimal Residual Disease (MRD) Network of the Fondazione Italiana Linfomi (FIL
MRD Network) has performed a comparative study of four different commercially
available kits for DNA extraction, applying them on a panel of cellular pellets,
with the aim of defining possible technical recommendations in order to harmonize
and standardize diagnostic procedures in the clinical setting. Overall, all four
kits usually allowed the recovery of a significant quantity of high-quality DNA
(in most conditions), although specific indications could be addressed for
cellular pellets of different sizes.
PMID- 25115510
TI - Lack of myeloproliferative neoplasm-associated CALR mutations in acute
promyelocytic leukemia.
PMID- 25115511
TI - Calreticulin gene mutations in myeloproliferative neoplasms without Janus kinase
2 mutations.
AB - Calreticulin, an endoplasmic reticulum protein with multiple functions involving
chaperone activity and calcium homeostasis, plays an important role in cellular
proliferation and differentiation. Calreticulin dysfunction is known to be
associated with different cancers. Very recently, calreticulin mutations have
been identified in myeloproliferative neoplasms (MPNs), with a particularly high
frequency in MPNs without Janus kinase 2 (JAK2) mutations, which exhibit clinical
characteristics different from those with mutant JAK2. Here, we focus on the
structure, function and carcinogenicity of calreticulin, as well as its
relationship with MPNs not involving JAK2 mutations.
PMID- 25115512
TI - PRDM1/BLIMP1: a tumor suppressor gene in B and T cell lymphomas.
AB - The gene encoding the human BLIMP1, prdm1, is located on chromosome 6q21, a locus
frequently deleted in lymphoid tumors. BLIMP1 is able to silence its target genes
in a context-dependent manner through different mechanisms. BLIMP1 is expressed
in both B and T cells, in which it plays important functions. In B cells, BLIMP1
acts as the master regulator of plasma cell differentiation, repressed by BCL6
and repressing both BCL6 and PAX5. In T cells, BLIMP1 is a critical factor for
most terminal effector cell differentiation in both CD4+ and CD8+ T cells. BLIMP1
is frequently inactivated in a variety of lymphomas, including diffuse large B
cell lymphomas, Natural Killer cell lymphoma and anaplastic large T cell
lymphoma. In this review, we will summarize the role of BLIMP1 in normal cells,
focusing on lymphoid cells, and on its function as tumor suppressor gene in
lymphomas.
PMID- 25115513
TI - Significance of 5,10-methylenetetrahydrofolate reductase gene variants in acute
lymphoblastic leukemia in Indian population: an experimental, computational and
meta-analysis.
AB - Acute lymphoblastic leukemia (ALL) arises due to several genetic alterations in
progenitor cells, and methotrexate is frequently used as part of the treatment
regimen. Although there is evidence for an effect of 5,10
methylenetetrahydrofolate reductase gene (MTHFR) C677T and A1298C variations on
drug response in ALL, its risk association for ALL is still unresolved. In a case
control study of 203 patients with ALL and 246 controls and meta-analysis in the
Indian population, we showed an insignificant association of MTHFR C677T and
A1298C genotypes with childhood and adult ALL. Comprehensive in silico
characterization of non-synonymous single nucleotide polymorphisms (nsSNPs) and
SNPs of the 3' untranslated region (UTR) revealed nine nsSNPs as deleterious, and
three SNPs in the 3'UTR could possibly alter the binding of miRNAs. The study
revealed that several overlooked SNPs may contribute to the risk of ALL
susceptibility and further studies of these SNPs with functional characterization
in a large sample size are required to understand the significant role of MTHFR
in ALL development.
PMID- 25115514
TI - Identification of linoleic acid, a main component of the n-hexane fraction from
Dryopteris crassirhizoma, as an anti-Streptococcus mutans biofilm agent.
AB - Dryopteris crassirhizoma is a semi-evergreen plant. Previous studies have shown
the potential of this plant as an agent for the control of cariogenic biofilms.
In this study, the main antibacterial components of the plant were identified by
correlating gas chromatography-mass spectrometry data with the antibacterial
activity of chloroform and n-hexane fractions and then evaluating the activity of
the most potent antibacterial component against Streptococcus mutans UA159
biofilms. The most potent antibacterial component was linoleic acid, a main
component of the n-hexane fraction. Linoleic acid reduced viability in a dose
dependent manner and reduced biofilm accumulation during initial and mature
biofilm formation. Furthermore, when the biofilms were briefly treated with
linoleic acid (10 min/treatment, a total of six times), the dry weight of the
biofilms was significantly diminished. In addition, the anti-biofilm activity of
the n-hexane fraction was similar to that of linoleic acid. These results suggest
that the n-hexane fraction of D. crassirhizoma and linoleic acid may be useful
for controlling cariogenic biofilms.
PMID- 25115516
TI - Membrane biofouling characterization: effects of sample preparation procedures on
biofilm structure and the microbial community.
AB - Ensuring the quality and reproducibility of results from biofilm structure and
microbial community analysis is essential to membrane biofouling studies. This
study evaluated the impacts of three sample preparation factors (ie number of
buffer rinses, storage time at 4 degrees C, and DNA extraction method) on the
downstream analysis of nitrifying biofilms grown on ultrafiltration membranes.
Both rinse and storage affected biofilm structure, as suggested by their strong
correlation with total biovolume, biofilm thickness, roughness and the spatial
distribution of EPS. Significant variations in DNA yields and microbial community
diversity were also observed among samples treated by different rinses, storage
and DNA extraction methods. For the tested biofilms, two rinses, no storage and
DNA extraction with both mechanical and chemical cell lysis from attached biofilm
were the optimal sample preparation procedures for obtaining accurate information
about biofilm structure, EPS distribution and the microbial community.
PMID- 25115515
TI - Growth and development of the barnacle Amphibalanus amphitrite: time and
spatially resolved structure and chemistry of the base plate.
AB - The radial growth and advancement of the adhesive interface to the substratum of
many species of acorn barnacles occurs underwater and beneath an opaque,
calcified shell. Here, the time-dependent growth processes involving various
autofluorescent materials within the interface of live barnacles are imaged for
the first time using 3D time-lapse confocal microscopy. Key features of the
interface development in the striped barnacle, Amphibalanus (= Balanus)
amphitrite were resolved in situ and include advancement of the
barnacle/substratum interface, epicuticle membrane development, protein
secretion, and calcification. Microscopic and spectroscopic techniques provide ex
situ material identification of regions imaged by confocal microscopy. In situ
and ex situ analysis of the interface support the hypothesis that barnacle
interface development is a complex process coupling sequential, timed secretory
events and morphological changes. This results in a multi-layered interface that
concomitantly fulfills the roles of strongly adhering to a substratum while
permitting continuous molting and radial growth at the periphery.
PMID- 25115517
TI - Identification and characterization of microbial biofilm communities associated
with corroded oil pipeline surfaces.
AB - Microbially influenced corrosion (MIC) has long been implicated in the
deterioration of carbon steel in oil and gas pipeline systems. The authors sought
to identify and characterize sessile biofilm communities within a high
temperature oil production pipeline, and to compare the profiles of the biofilm
community with those of the previously analyzed planktonic communities.
Eubacterial and archaeal 16S rRNA sequences of DNA recovered from extracted
pipeline pieces, termed 'cookies,' revealed the presence of thermophilic
sulfidogenic anaerobes, as well as mesophilic aerobes. Electron microscopy and
elemental analysis of cookies confirmed the presence of sessile cells and
chemical constituents consistent with corrosive biofilms. Mass spectrometry of
cookie acid washes identified putative hydrocarbon metabolites, while surface
profiling revealed pitting and general corrosion damage. The results suggest that
in an established closed system, the biofilm taxa are representative of the
planktonic eubacterial and archaeal community, and that sampling and monitoring
of the planktonic bacterial population can offer insight into biocorrosion
activity. Additionally, hydrocarbon biodegradation is likely to sustain these
communities. The importance of appropriate sample handling and storage procedures
to oilfield MIC diagnostics is highlighted.
PMID- 25115518
TI - Fouling in your own nest: vessel noise increases biofouling.
AB - Globally billions of dollars are spent each year on attempting to reduce marine
biofouling on commercial vessels, largely because it results in higher fuel costs
due to increased hydrodynamic drag. Biofouling has been long assumed to be
primarily due to the availability of vacant space on the surface of the hull.
Here, it is shown that the addition of the noise emitted through a vessel's hull
in port increases the settlement and growth of biofouling organisms within four
weeks of clean surfaces being placed in the sea. More than twice as many
bryozoans, oysters, calcareous tube worms and barnacles settled and established
on surfaces with vessel noise compared to those without. Likewise, individuals
from three species grew significantly larger in size in the presence of vessel
noise. The results demonstrate that vessel noise in port is promoting biofouling
on hulls and that underwater sound plays a much wider ecological role in the
marine environment than was previously considered possible.
PMID- 25115519
TI - Presence and function of a thick mucous layer rich in polysaccharides around
Bacillus subtilis spores.
AB - This study was designed to establish the presence and function of the mucous
layer surrounding spores of Bacillus subtilis. First, an external layer of
variable thickness and regularity was often observed on B. subtilis spores.
Further analyses were performed on B. subtilis 98/7 spores surrounded by a thick
layer. The mechanical removal of the layer did not affect their resistance to
heat or their ability to germinate but rendered the spore less hydrophilic, more
adherent to stainless steel, and more resistant to cleaning. This layer was
mainly composed of 6-deoxyhexoses, ie rhamnose, 3-O-methyl-rhamnose and
quinovose, but also of glucosamine and muramic lactam, known also to be a part of
the bacterial peptidoglycan. The specific hydrolysis of the peptidoglycan using
lysozyme altered the structure of the required mucous layer and affected the
physico-chemical properties of the spores. Such an outermost mucous layer has
also been seen on spores of B. licheniformis and B. clausii isolated from food
environments.
PMID- 25115520
TI - The significance of calcium ions on Pseudomonas fluorescens biofilms - a
structural and mechanical study.
AB - The purpose of this study was to investigate the effects of calcium ions on the
structural and mechanical properties of Pseudomonas fluorescens biofilms grown
for 48 h. Advanced investigative techniques such as confocal laser scanning
microscopy and atomic force spectroscopy were employed to characterize biofilm
structure as well as biofilm mechanical properties following growth at different
calcium concentrations. The presence of calcium during biofilm development led to
higher surface coverage with distinct structural phenotypes in the form of a
granular and heterogeneous surface, compared with the smoother and homogeneous
biofilm surface in the absence of calcium. The presence of calcium also increased
the adhesive nature of the biofilm, while reducing its elastic properties. These
results suggest that calcium ions could have a functional role in biofilm
development and have practical implications, for example, in analysis of
biofouling in membrane-based water-treatment processes such as nanofiltration or
reverse osmosis where elevated calcium concentrations may occur at the solid
liquid interface.
PMID- 25115521
TI - Antifouling properties of zinc oxide nanorod coatings.
AB - In laboratory experiments, the antifouling (AF) properties of zinc oxide (ZnO)
nanorod coatings were investigated using the marine bacterium Acinetobacter sp.
AZ4C, larvae of the bryozoan Bugula neritina and the microalga Tetraselmis sp.
ZnO nanorod coatings were fabricated on microscope glass substrata by a simple
hydrothermal technique using two different molar concentrations (5 and 10 mM) of
zinc precursors. These coatings were tested for 5 h under artificial sunlight
(1060 W m(-2) or 530 W m(-2)) and in the dark (no irradiation). In the presence
of light, both the ZnO nanorod coatings significantly reduced the density of
Acinetobacter sp. AZ4C and Tetraselmis sp. in comparison to the control
(microscope glass substratum without a ZnO coating). High mortality and low
settlement of B. neritina larvae was observed on ZnO nanorod coatings subjected
to light irradiation. In darkness, neither mortality nor enhanced settlement of
larvae was observed. Larvae of B. neritina were not affected by Zn(2+) ions. The
AF effect of the ZnO nanorod coatings was thus attributed to the reactive oxygen
species (ROS) produced by photocatalysis. It was concluded that ZnO nanorod
coatings effectively prevented marine micro and macrofouling in static
conditions.
PMID- 25115522
TI - I am pregnant and want to do better but i can't: focus groups with low-income
overweight and obese pregnant women.
AB - This study was conducted to identify factors that influenced stress, healthy
eating and physical activity among low-income overweight or obese pregnant women.
We conducted seven focus groups with 96 low-income overweight and obese pregnant
women. Common themes were identified from audio tapes and transcripts. Women said
that poor communication affected their relationships with spouses or significant
others. They were frustrated or upset with significant others for three key
reasons: failure to understand or listen to the pregnant women's pregnancy
concerns, refusal to be helpful when asked and being overly concerned with the
woman's safety. Most women said that they were emotional and took naps throughout
the day after becoming pregnant. Many withdrew from their social interactions.
They also faced numerous challenges that made healthy eating more difficult,
e.g., craving for unhealthy foods and eating foods for comfort. To eat healthier,
some reminded themselves to avoid overeating or stop eating in the car. Women
were not physically active because of tiredness, lack of motivation, inadequate
social support, or bad weather. Some stayed physically active to prevent
excessive pregnancy weight gain and have an easier labor. Women equivocally said
weighing themselves to manage weight would add to their stress and make them feel
more depressed. When designing interventions to help low-income overweight and
obese pregnant women avoid excessive pregnancy weight gain, it is important to
include information and practical advice on stress management, emphasizing
effective communication skills with significant others and helping them plan
effective ways to manage negative feelings.
PMID- 25115523
TI - Inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase increases the
expression of interferon-responsive genes.
AB - The 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) pathway is an
important metabolic route that is present in almost every organism. However,
whether HMGCR affects the expression of interferon (IFN)-responsive genes is
unclear. In the present study, expression levels of IFN-responsive genes were
monitored by real time polymerase chain reaction and enzyme-linked immunosorbent
assay. The results showed that expression levels of IFN-responsive genes were
significantly increased in HMGCR-downregulated cells and HMGCR inhibitor-treated
cells, indicating that inhibition of HMGCR activates the expression of IFN
responsive genes. The result in this study will provide new insight into the role
of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in antiviral research.
PMID- 25115524
TI - Congenital microcephaly and chorioretinopathy due to de novo heterozygous KIF11
mutations: five novel mutations and review of the literature.
AB - The microcephaly-lymphedema-chorioretinal dysplasia (MLCRD) syndrome is a
distinct microcephaly syndrome. The hallmark features, microcephaly,
chorioretinopathy, and lymphedema are frequently recognized at birth. Another
clinical entity, the chorioretinal dysplasia, microcephaly and mental retardation
syndrome (CDMMR) is a highly overlapping syndrome characterized by more variable
lymphedema. Recently, heterozygous mutations in KIF11, a gene encoding a critical
spindle motor protein of the Kinesin family, have been reported in individuals
with MLCRD, and in individuals with CDMMR. This finding is suggestive of a single
clinically variable spectrum. Here, we report on de novo novel mutations of KIF11
in five individuals with severe microcephaly, marked simplification of the gyral
pattern on neuroimaging, bilateral chorioretinopathy, and developmental delay.
Three patients had congenital lymphedema, and one had congenital bilateral
sensorineural hearing loss. This report, therefore, further expands the clinical
and molecular spectrum of KIF11-associated microcephaly.
PMID- 25115526
TI - Nontuberculous mycobacterial infection in a clinical presentation of Fitz-Hugh
Curtis syndrome: a case report with multigene diagnostic approach.
AB - BACKGROUND: Fitz-Hugh-Curtis syndrome (FHCS) is caused by inflammation of
perihepatic capsules associated with pelvic inflammatory disease. In recent
years, infections with nontuberculous mycobacteria (NTM) have been increasingly
occurring in immunocompromised and immunocompetent patients. However, NTM has
never been reported in patients with FHCS. We present the first case of a patient
with extrapulmonary NTM infection in a clinical presentation of FHCS. CASE
PRESENTATION: A 26-year-old Korean woman presented with right upper quadrant and
suprapubic pain. She was initially suspected to have FHCS. However, she was
refractory to conventional antibiotic therapy. Laparoscopy revealed multiple
violin-string adhesions of the parietal peritoneum to the liver and miliary-like
nodules on the peritoneal surfaces. Diagnosis of NTM was confirmed by the
polymerase chain reaction analysis results of biopsy specimens that showed
caseating granulomas with positive acid-fast bacilli. Treatment with anti-NTM
medications was initiated, and the patient's symptoms were considerably
ameliorated. CONCLUSIONS: An awareness of NTM as potential pathogens, even in
previously healthy adults, and efforts to exclude other confounding diseases are
important to establish the diagnosis of NTM disease. NTM infection can cause
various clinical manifestations, which in the present case, overlapped with the
symptoms of perihepatic inflammation seen in FHCS.
PMID- 25115527
TI - Response to: "Oral manifestations and blood profile in patients with iron
deficiency anemia".
PMID- 25115528
TI - Oral manifestations and blood profile in patients with iron deficiency anemia.
PMID- 25115529
TI - Mobile phone use and health symptoms in children.
AB - BACKGROUND/PURPOSE: To investigate the mobile phone (MP) use for talking in
relation to health symptoms among 2042 children aged 11-15 years in Taiwan.
METHODS: A nationwide, cross-sectional study, using the computer assisted
telephone interview (CATI) technique, was conducted in 2009 to collect
information on children's utilization of MPs and the perceived health symptoms
reported by their parents. RESULTS: The overall prevalence of MP use in the past
month was estimated at 63.2% [95% confidence interval (CI) = 61.1-65.3%]. MP use
was associated with a significantly increased adjusted odds ratio (AOR) for
headaches and migraine (1.42, 95% CI = 1.12-1.81) and skin itches (1.84, 95% CI =
1.47-2.29). Children who regularly used MPs were also considered to have a health
status worse than it was 1 year ago (beta = 0.27, 95% CI = 0.17-0.37).
CONCLUSION: Although the cross-sectional design precludes the causal inference
for the observed association, our study tended to suggest a need for more
cautious use of MPs in children, because children are expected to experience a
longer lifetime exposure to radiofrequency electromagnetic fields (RF-EMF) from
MPs.
PMID- 25115530
TI - A novel anabolic agent: a simvastatin analogue without HMG-CoA reductase
inhibitory activity.
AB - For the first time, structural information regarding the role of simvastatin in
bone anabolism is described, and a bone-specific statin is introduced.
Polyaspartate-conjugated simvastatin was synthesized by solid-phase synthesis
with the assistance of microwave irradiation. It displays significant bone
targeting and bone formation with less toxicity than simvastatin.
PMID- 25115531
TI - Epidemiology of varicella zoster virus infection in Canada and the United Kingdom
- CORRIGENDUM.
PMID- 25115537
TI - Comparison of temporal muscle fascia and cartilage grafts in pediatric
tympanoplasties.
AB - OBJECTIVE: To compare anatomic and functional outcomes of the different graft
materials used in pediatric tympanoplasty. MATERIALS AND METHODS: The patients
younger than 18 years of age and who had tympanoplasty between 2010 and 2012 were
included in the study. Temporal muscle fascia or cartilage was used as the graft
material. The age, gender, the side of the operated ear, the operation technique,
pre- and postoperative audiological results, and the status of the graft were
noted. An intact graft and an air-bone gap (ABG) <= 20 were regarded as surgical
success in the postoperative period. Audiograms obtained before surgery and 1
year after surgery were used for the comparison. RESULTS: Sixty pediatric cases
were included in the study. Fascia graft was used as the graft material in 35 of
them, and cartilage was used in 25 patients. The graft success rate was 82.9% in
the fascia group while it was 92% in the cartilage group. In the fascia group
preoperative ABG was 28.2 +/- 10.1 dB, postoperative ABG was 15.1 +/- 10.2dB, and
postoperative gain was 13.1 +/- 9.6 dB. In the cartilage group, preoperative ABG
was 28.9 +/- 10.2dB, and postoperative ABG was 16.8 +/- 10.3 dB with a
postoperative gain of 12.1 +/- 6.8 dB. The differences between the fascia and the
cartilage groups were not statistically significant either for hearing gain or
graft success rate. CONCLUSION: Cartilage and fascia grafts yield similar results
for hearing gain and graft success rate in pediatric tympanoplasty.
PMID- 25115538
TI - Reproducibility and repeatability of ganglion cell-inner plexiform layer
thickness measurements in healthy subjects.
AB - PURPOSE: To assess the reproducibility and repeatability of macular ganglion cell
inner plexiform layer (GC-IPL) thickness measurements in healthy subjects.
PROCEDURES: In this observational study, 60 healthy eyes were subjected to
macular GC-IPL thickness measurements by means of CirrusTM high-definition
optical coherence tomography (Cirrus version 6.0; Carl Zeiss Meditec, Dublin,
Calif., USA) by two examiners in two sessions. Average, minimum and 6 sectoral GC
IPL thicknesses were measured. Inter- and intraobserver reproducibility was
tested and analyzed by means of the concordance correlation coefficient (CCC).
The repeatability of measurements was assessed by the coefficient of
repeatability (CR). RESULTS: Mean age (+/-SD) was 29.63 (+/-5.1) years. The CRs
for average GC-IPL thickness were 2.1 and 2.2 um for the first and the second
operator, respectively. Inter- and intraobserver CCCs ranged from 0.91 (95% CI:
0.89-0.93) to 0.98 (95% CI: 0.96-0.99) and from 0.92 (95% CI: 0.88-0.94) to 0.98
(95% CI: 0.97-0.99), respectively. CONCLUSIONS: GC-IPL thickness measurements in
young healthy subjects showed excellent reproducibility and repeatability,
especially for average and sectoral GC-IPL thickness measurements.
PMID- 25115539
TI - Bone loss and osteoporosis are associated with conversion from mild cognitive
impairment to Alzheimer's disease.
AB - OBJECTIVE: The aim of this study was to analyze the relationship between low bone
mineral density (BMD) and conversion from mild cognitive impairment (MCI) to
Alzheimer's disease (AD) dementia in a Chinese cohort. METHODS: Men and women
(n=946) aged 60-75 underwent a dual X-ray absorptiometry (DXA) study of the
lumbar spine and hip and were followed annually for 5 years. Their cognitive and
functional status were assessed using the Chinese version of the Mini-Mental
State Examination (MMSE) and an assessment of the instrumental activities of
daily living (ADL). RESULTS: There was a positive relationship between
osteoporosis and a decline in cognition and function (P<0.001) based on MMSE and
ADL scores. The subjects with BMD values in the lowest quartile had a 2-fold
increased risk of AD conversion compared with the controls. These results suggest
that severe BMD loss is associated with an increased risk of AD conversion in
both women and men. CONCLUSIONS: Osteoporosis was associated with an increased
risk of incident AD dementia. Additionally, low BMD at baseline was associated
with an increased risk of AD in both women and men.
PMID- 25115540
TI - Metabotropic glutamate receptor 5 in Down's syndrome hippocampus during
development: increased expression in astrocytes.
AB - Metabotropic glutamate receptor 5 (mGluR5) is highly expressed throughout the
forebrain and hippocampus. Several lines of evidence support the role of this
receptor in brain development and developmental disorders, as well as in
neurodegenerative disorders like Alzheimer's disease (AD). In the present study,
the expression pattern of mGluR5 was investigated by immunocytochemistry in the
developing hippocampus from patients with Down's syndrome (DS) and in adults with
DS and AD. mGluR5 was expressed in developing human hippocampus from the earliest
stages tested (9 gestational weeks), with strong expression in the
ventricular/subventricular zones. We observed a consistent similar temporal and
spatial neuronal pattern of expression in DS hippocampus. However, in DS we
detected increased prenatal mGluR5 expression in white matter astrocytes, which
persisted postnatally. In addition, in adult DS patients with widespread
ADassociated neurodegeneration (DS-AD) increased mGluR5 expression was detected
in astrocytes around amyloid plaque. In vitro data confirm the existence of a
modulatory crosstalk between amyloid-beta and mGluR5 in human astrocytes. These
findings demonstrate a developmental regulation of mGluR5 in human hippocampus
and suggest a role for this receptor in astrocytes during early development in DS
hippocampus, as well as a potential contribution to the pathogenesis of
ADassociated pathology.
PMID- 25115542
TI - Fluoxetine improves behavioral performance by suppressing the production of
soluble beta-amyloid in APP/PS1 mice.
AB - Alzheimer's disease (AD) is the most common neurodegenerative disorder of the
central nervous system. Current approaches for AD treatment only ameliorate
symptoms. Therapeutic strategies that target the pathological processes of the
disease remain elusive. Fluoxetine (FLX) is one of the most widely used
antidepressants for the treatment of depression and anxiety associated with AD,
however, it is unknown if the drug affects the pathogenesis of the disease. We
showed that FLX improved spatial memory, learning and emotional behaviors of
APP/PS1 mice, a well characterized model of AD. In the same mice, FLX effectively
prevented the protein loss of synaptophysin (SYP) and microtubuleassociated
protein 2 (MAP2). FLX was unable to prevent plaque formation, but significantly
lowered high levels of soluble beta-amyloid (Abeta) in brain tissue,
cerebrospinal fluid (CSF) and blood sera. FLX also effectively inhibited the
phosphorylation of amyloid precursor protein (APP) at T668, which may be a
possible mechanism of the reduced Abeta production in APP/PS1 mouse after
treatment.
PMID- 25115541
TI - Severe psychiatric disorders in mid-life and risk of dementia in late- life (age
65-84 years): a population based case-control study.
AB - OBJECTIVE: To examine the association of mid-life exposure to several psychiatric
disorders with the development of late-life dementia. METHODS: A matched case
control study using Western Australian state-wide hospital inpatient, outpatient
mental health and emergency records linked to death records. Incident dementia
cases (2000-2009) aged 65 to 84 years were sex- and age-matched to an electoral
roll control. Records as far back as 1970 were used to assess exposure to medical
risk factors before age 65 years. Candidate psychiatric risk factors were
required to be present at least 10 years before dementia onset to ensure
direction of potential causality. Odds ratios were estimated using conditional
logistic regression. RESULTS: 13, 568 dementia cases (median age 78.7 years, 43.4
% male) were matched to a control. Depression, bipolar disorder, schizophrenia,
anxiety disorder and alcohol dependence were found to be significant and
independent risk factors for late-life dementia after adjusting for diabetes,
heart disease, cerebrovascular disease and smoking risk factors. The effect of a
history of depression, schizophrenia and alcohol dependency on dementia risk
varied with age, being strongest for earlier onset late-life dementia and waning
at older ages. CONCLUSION: Severe depression, anxiety disorder, bipolar disorder,
schizophrenia and alcoholic dependency disorder treated by specialists in
psychiatric facilities in mid-life are important risk factors for late-life
dementia. These psychiatric conditions need to be considered in future studies of
the risk and prevention of late-life dementia.
PMID- 25115543
TI - Intraventricular human immunoglobulin distributes extensively but fails to modify
amyloid in a mouse model of amyloid deposition.
AB - Intravenous immunoglobulin infusions into Alzheimer patients have been found to
provide cognitive benefit over a period of 6 mo in open label studies. One
suggestion has been that these preparations contain small amounts of antibodies
directed against monomeric and oligomeric Abeta which underlie their
effectiveness in patients. To test this hypothesis, we infused Gammagard, a
version of intravenous immunoglobulin (IVIG), into the lateral ventricle of
amyloid precursor protein (APP) transgenic mice with pre-existing amyloid
deposits. Mice were infused over 4 weeks, and tested behaviorally for the last 2
weeks of treatment. Brains were analyzed for histopathology. We found widespread
distribution of human-immunoglobulin G (h-IgG) staining in the mouse forebrain,
including cerebral cortices and hippocampus. Some cortical neurons appeared to
concentrate the h-IgG, but we did not detect evidence of amyloid plaque labeling
by h-IgG. The IVIG-treated mice had no change in phenotype compared to saline
infused animals with respect to activity, learning and memory, or amyloid
deposition. APP mice infused with an anti-Abeta monoclonal antibody did show some
reduction in amyloid deposits. These data do not support the argument that anti
Abeta antibodies in IVIG preparations are responsible for cognitive benefits seen
with these preparations.
PMID- 25115544
TI - Intravenous immunoglobulin treatment preserves and protects primary rat
hippocampal neurons and primary human brain cultures against oxidative insults.
AB - Alzheimer's disease (AD) is characterized by deleterious accumulation of amyloid
beta (Abeta) peptide into senile plaque, neurofibrillary tangles formed from
hyperphosphorylated tau protein, and loss of cholinergic synapses in the cerebral
cortex. The deposition of Abeta-loaded plaques results in microglial activation
and subsequent production of reactive oxygen species (ROS), including free
radicals. Neurons in aging and AD brains are particularly vulnerable to ROS and
other toxic stimuli. Therefore, agents that decrease the vulnerability of neurons
against ROS may provide therapeutic values for the treatment or prevention of AD.
In the present study, our goal was to test whether intravenous immunoglobulin
(IVIG) treatment could preserve as well as protect neurons from oxidative damage.
We report that treatment with IVIG protects neuronal viability and synaptic
proteins in primary rat hippocampal neurons. Further, we demonstrate the
tolerability of IVIG treatment in the primary human fetal mixed brain cultures.
Indeed, a high dose (20 mg/ml) of IVIG treatment was well-tolerated by primary
human brain cultures that exhibit a normal neuronal phenotype. We also observed a
potent neuropreservatory effect of IVIG against ROS-mediated oxidative insults in
these human fetal brain cultures. These results indicate that IVIG treatment has
great potential to preserve and protect primary human neuronal-enriched cultures
and to potentially rescue dying neurons from oxidative insults. Therefore, our
findings suggest that IVIG treatment may represent an important therapeutic agent
for clinical trials designed to prevent and delay the onset of neurodegeneration
as well as AD pathology.
PMID- 25115545
TI - Role of complement systems in IVIG mediated attenuation of cognitive
deterioration in Alzheimer's disease.
AB - Human intravenous immunoglobulin (IVIG) has been indicated as a potential therapy
for autoimmune neurological disorders, as well as in many neurodegenerative
diseases, with various underlying therapeutic mechanisms such as regulation of T
cell trafficking, cytokines, Fc receptor blocking, and interruption of complement
activation cascade. In Alzheimer's disease (AD), IVIG presents naturally
occurring antibodies against amyloid-beta (Abeta) aggregation, thus IVIG
immunotherapy may increase the clearance of Abeta and protect brain function.
Recently, we and others reported that besides Abeta clearance, IVIG specifically
regulates the levels of complement-derived anaphylatoxins, such as C5a and C3,
which play an important role in the regulation of AMPA and NMDA receptor
expression in the brain and further upregulate the AMPA-PKA-CREB signaling
pathway and synaptic function in AD mouse models. Since down-regulation of
complement components has been linked with deficits of cognitive function in age
related dementia following the decline of innate immunity during aging, the IVIG
immunotherapy could be an attractive novel AD therapeutic through its local
regulation of C3, C5a component levels in brain.
PMID- 25115546
TI - Intravenous immunoglobulins for Alzheimer's disease.
AB - Alzheimer's disease (AD) is a chronic neurodegenerative disease associated with
intracerebral accumulation of aggregated amyloid-beta (Abeta) and tau proteins,
as well as neuroinflammation. Human intravenous immunoglobulin (IVIG) is a
mixture of polyclonal IgG antibodies isolated and pooled from thousands of
healthy human donors. The scientific rationale for testing IVIG as a potential AD
treatment include its natural anti-Abeta antibody activity, its favorable safety
profile and inherent anti-inflammatory/immunomodulatory properties. Over the past
decade, several clinical and pre-clinical experimental findings, advanced our
knowledge about biological and therapeutic properties of IVIG that are relevant
to AD therapy. Anti-amyloid antibodies in IVIG show significantly higher binding
avidity for amyloid oligomers and fibrils than for Abeta monomers. In a double
transgenic murine model of AD, intracerebral injection of IVIG causes suppression
of Abeta fibril pathology whereas long term peripheral IVIG treatments causes
elevation of total brain Abeta levels with no measurable impact on Abeta deposits
or tendency for inducing cerebral microhemmorhage. Furthermore, chronic IVIG
treatment suppressed neuroinflammation and fostered adult hippocampal
neurogenesis. In clinical studies with AD patients, IVIG showed an acceptable
safety profile and has not been reported to increase the incidence of amyloid
related imaging abnormalities. Preliminary studies on small number of patients
reported clinical benefits in mild to moderate stage AD patients. However, double
blind, placebo controlled studies later did not replicate those initial findings.
Interestingly though, in APOE4 carriers and in moderate disease stage subgroups,
positive cognitive signals were reported. Nevertheless, both clinical and
experimental (mouse) studies show that antibodies in IVIG can accumulate in CNS
and its biological activities include neutralization of Abeta oligomers,
suppression of neuroinflammation and immunomodulation. Identifying mediators of
IVIG's effects at the cellular and molecular level is warranted. In light of its
favourable safety profile and aforementioned biological properties, IVIG is still
an enigmatic experimental candidate with enormous potential for being an AD
therapeutic.
PMID- 25115548
TI - Pyloric gland adenoma observed by magnifying endoscopy with narrow-band imaging.
PMID- 25115547
TI - Homocysteine and nitrite levels are modulated by MTHFR 677C>T polymorphism in
obese women treated with simvastatin.
AB - Higher homocysteine (Hcy) levels are associated with cardiovascular risk. The aim
of the present study was to evaluate the effect of simvastatin treatment on
circulating Hcy levels in obese women without hypertension, diabetes or
dyslipidaemia; and to determine whether the 677C>T polymorphism located in
methylenetetrahydrofolate reductase (NAD(P)H) (MTHFR) gene modulates the effects
of this treatment on Hcy and nitrite (as a biomarker of nitric oxide (NO)
bioavailability). Twenty-five obese women (body mass index >= 30 kg/m(2) ) who
had received 20 mg/day simvastatin for 6 weeks were enrolled in the study. Venous
blood samples were collected to measure plasma biomarkers and gene polymorphisms.
Simvastatin treatment significantly reduced total cholesterol, low-density
lipoprotein-cholesterol, thiobarbituric acid-reactive substances, high
sensitivity C-reactive protein and Hcy, whereas nitrite levels were increased.
The reduction in Hcy levels in carriers of the T allele was -20.3% compared with
9.4% in patients with the CC genotype. Importantly, before treatment, nitrite
levels were significantly higher in patients with the CC genotype compared with T
allele carriers, whereas after treatment these levels were similar between
groups. Our findings demonstrate that obese women without comorbidities and
carrying the T variant of the 677C>T polymorphism of MTHFR exhibit benefits with
simvastatin treatment, mainly in terms of increased NO levels.
PMID- 25115549
TI - Do the genes of the innate immune response contribute to neuroprotection in
Drosophila?
AB - A profound debate exists on the relationship between neurodegeneration and the
innate immune response in humans. Although it is clear that such a relation
exists, the causes and consequences of this complex association remain to be
determined in detail. Drosophila is being used to investigate the mechanisms
involved in neurodegeneration, and all genomic studies on this issue have
generated gene catalogues enriched in genes of the innate immune response. We
review the data reported in these publications and propose that the abundance of
immune genes in studies of neurodegeneration reflects at least two phenomena: (i)
some proteins have functions in both immune and nervous systems, and (ii) immune
genes might also be of neuroprotective value in Drosophila. This review opens
this debate in Drosophila, which could thus be used as an instrumental model to
elucidate this question.
PMID- 25115550
TI - (18)F-fluorodeoxyglucose uptake in brown adipose tissue during insulin-induced
hypoglycemia and mild cold exposure in non-diabetic adults.
AB - OBJECTIVE: Hypoglycemia is associated with increased heat production and, despite
of this, hypothermia. Heat production is likely to be mediated by sympathetic
innervation. Brown adipose tissue is activated by cold exposure and stimulated by
the sympathetic nervous system. We therefore examined the effect of hypoglycemia
on uptake of the labeled glucose analogue (18)F-fluorodeoxyglucose in brown
adipose tissue using positron emission tomography and computer tomography.
METHODS: In nine healthy adults (18)F-fluorodeoxyglucose uptake as measure of
brown adipose tissue activity was assessed in a cold environment (17 degrees C)
during euglycemia (blood glucose 4.5 mmol/L) and hypoglycemia (2.5 mmol/L) using
a hyperinsulinemic glucose clamp. RESULTS: Brown adipose tissue activity was
observed in all participants. No difference was observed in the median (range)
maximal standardized uptake values of (18)F-fluorodeoxyglucose in brown adipose
tissue between euglycemia and hypoglycemia: 4.2 (1.0-7.7) versus 3.1 (2.2-12.5)
g/mL (p=0.7). Similarly there were no differences in mean standardized (18)F
fluorodeoxyglucose uptake values or total brown adipose tissue volume between
euglycemia and hypoglycemia. Body temperature dropped by 0.6 degrees C from
baseline during the hypoglycemic condition and remained unchanged during the
euglycemic condition. There was no correlation between the maximal standardized
uptake values of (18)F-fluorodeoxyglucose in brown adipose tissue and levels of
counterregulatory hormones. CONCLUSIONS: This study shows that there is a similar
amount of (18)F-fluorodeoxyglucose uptake in brown adipose tissue during
hypoglycemia when compared to euglycemia, which makes a role for systemic
catecholamines in brown adipose tissue activation and a role for brown adipose
tissue thermogenesis in hypoglycemia associated hypothermia unlikely. Future
studies in humans should determine whether hypoglycemia indeed increases energy
expenditure, and if so which alternative source can explain this increase.
PMID- 25115551
TI - [Studies on markers of exposure and early effect in areas with arsenic pollution:
methods and results of the project SEpiAs. Epidemiological studies on population
exposed to low-to-moderate arsenic concentration in drinking water].
AB - Arsenic and its inorganic compounds are classified as human carcinogens. Several
epidemiological studies conducted in areas of the world characterized by high
arsenic concentration in drinking water, even up to 3,000 MUg/l, report
associations between arsenic exposure and skin, bladder, lung, liver and kidney
cancer as well as cardiovascular diseases, diabetes and reproductive and
developmental effects. Since general population is not exposed to these high
arsenic concentrations in the last years attention focused on adverse health
effects that low-to-moderate arsenic concentrations (0-150 MUg/l) in drinking
water could induce. The World Health Organization recommends a maximum limit of
10 MUg/l for arsenic in drinking water. Almost all epidemiological studies
conducted on populations exposed to low-to-moderate arsenic concentrations in
drinking water are limited due to problems arising from both individual exposure
assessment and low subjects number. The aim of the present review is to collect
literature-based evidences regarding adverse health effects associated with
exposure to low-to-moderate arsenic concentrations in drinking water (10-150
MUg/l) in order to obtain a comprehensive picture of the health outcomes that
such exposure can have on general population.
PMID- 25115553
TI - Circulating Endothelial Cells and Platelet Microparticles in Mitral Valve Disease
With and Without Atrial Fibrillation.
AB - Hypercoagulability in mitral valve disease (MVD), a cause of atrial fibrillation
(AF) and stroke, is potentially due to endothelial damage/dysfunction (marked by
circulating endothelial cells [CECs]), platelet activation (soluble P-selectin
[sPsel], platelet microparticles [PMPs], and soluble CD40 [sCD40]), and oxidized
low-density lipoprotein (oxLDL) cholesterol. We measured these variables in 24
patients with MVD as well as in 21 with MVD + AF and compared them with 20
healthy controls (HCs). The CECs and PMPs were measured by flow cytometry; sPsel,
oxLDL, and CD40 by enzyme-linked immunosorbent assay. Compared with HCs, sPsel
and PMPs were equally higher in MVD and MVD + AF; sCD40 and oxLDL were higher in
MVD + AF than in HCs and MVD; and CECs were higher in MVD than in the HCs, with
further increases in MVD + AF (all P < .001). We conclude that excess platelet
activation is present in MVD regardless of AF, and that increased endothelial
damage in MVD is greater when compounded by AF.
PMID- 25115554
TI - Long-Term Follow-Up of Patients at High Risk for Nephropathy After Contrast
Exposure.
AB - Contrast medium-induced acute kidney injury (CI-AKI) is associated with morbidity
and mortality, but the long-term outcomes of patients who do not develop CI-AKI
remain unknown. We assessed clinical end points during long-term follow-up in
patients at high risk for nephropathy who did not develop CI-AKI. Patients (n =
135) with impaired renal function (estimated glomerular filtration rate: 30-60
mL/min/1.73 m(2)) were divided into 2 groups according to contrast media (CM)
exposure. The primary end point of this study was a composite outcome measure of
death or renal failure requiring dialysis. Multivariate analyses identified CM
exposure to be independently associated with major adverse long-term outcomes
(hazard ratio: 2.3; 95% confidence interval, 1.34-6.52; P = .018). Even when CM
exposure does not cause CI-AKI in patients with impaired renal function, in the
long term, primary end points occur more frequently in patients exposed to CM
than in those with no CM exposure.
PMID- 25115552
TI - [Studies on markers of exposure and early effect in areas with arsenic pollution:
methods and results of the project SEpiAs. Epidemiological surveillance in areas
with environmental pollution by natural or anthropogenic arsenic].
AB - INTRODUCTION: Arsenic and its inorganic compounds are classified as carcinogenic
to humans. Exposures to inorganic arsenic (iAs) in drinking water are associated
with both carcinogenic and non-carcinogenic effects. The risk assessment of
exposures to low-moderate levels of environmental arsenic (As) is a challenging
objective for research and public health. The SEpiAs study, funded by the Italian
Ministry of Health (CCM), was carried out in four areas with arsenic pollution
prevalently of natural origin, Amiata and Viterbo areas, or of industrial origin,
Taranto and Gela. MATERIALS AND METHODS: 271 subjects (132 men) aged 20-44, were
randomly sampled stratifying by area, gender and age classes. Individual data on
residential history, socio-economic status, environmental and occupational
exposures, lifestyle and dietary habits, were collected through interviews using
questionnaire. In urine samples of recruited subjects, the concentration of
inorganic arsenic (iAs) and methylated species (MMA, DMA) was measured using
inductively coupled mass spectrometer (DRCICP- MS), after chromatographic
separation (HPLC). Molecular biomarkers and biomarkers of DNA damage, as well as
markers of cardiovascular risk were measured The distributions of iAs and
iAs+MMA+DMA were described by area and gender, geometric mean (GM), percentiles
and standard deviation (SD). The associations between As species and variables
collected by questionnaire were evaluated by multiple regression analysis.
RESULTS: Results showed a high variability of As species within and among areas.
Gela and Taranto samples showed higher iAs concentration compared to Viterbo and
Amiata. Subjects with iAs>1,5 MUg/L or iAs+MMA+DMA>15 MUg/L (thresholds suggested
by the Italian Society of Reference Values), are 137 (50,6%) and 68 (25,1%),
respectively. A positive association between iAs and use of drinking water
emerged in the Viterbo sample, between iAs and occupational exposure in the Gela
and Taranto samples. Fish consumption was associated with higher iAs
concentration in the whole sample, and particularly in men of the Gela sample.
Similar results were observed for iAs+MMA+DMA. Subjects with iAs or iAs+MMA+DMA
values higher than the 95th percentile were 15 (6Taranto, 5 Gela, 3Viterbo, 1
Amiata). The relationships between iAs and organic species (methylation
efficiency ratios) were different between sex in the four areas. The relevance of
polymorphisms AS3MT Met287Thr, GST-T1, GST-M1, OGG1 was confirmed. The analysis
of carotid intima-media-thickness showed normal values, but higher among man of
Viterbo, Taranto and Gela areas. CONCLUSIONS: Results are informative of exposure
to inorganic and organic As in large or at least non-negligible quotas of the
samples. The SEpiAs results suggest a further deepening on routes of exposure to
arsenic species, and support the recommendation to implement primary prevention
measures to reduce population exposure.
PMID- 25115555
TI - Reduced Protein C Activity Might be Associated With Progression of Peripheral
Arterial Disease.
AB - We evaluated the effect of reduced activities of protein C (PC) and protein S
(PS) on the progression of peripheral arterial disease (PAD). We measured PC and
PS activities in 106 patients with PAD and 44 patients with abdominal aortic
aneurysm (AAA) in the same period. The incidences of PC deficiency in PAD and AAA
were 4.7% and 4.5%, respectively, and those of PS were 14.1% and 11.4%,
respectively; these incidences were much higher than those in the normal
population. The PC and PS activities were significantly lower in patients having
critical limb ischemia (CLI) than in patients with intermittent claudication. In
particular, lower PC activity and female gender were determinant factors of CLI
in multivariate logistic regression analysis. We suggest that PC deficiency is an
independent predictor for the progression of CLI.
PMID- 25115558
TI - Structural properties of iron-phosphate glasses: spectroscopic studies and ab
initio simulations.
AB - Vitrification is the most effective method for the immobilization of hazardous
waste by incorporating toxic elements into a glass structure. Iron phosphate
glasses are presently being considered as matrices for the storage of radioactive
waste, even of those which cannot be vitrified using conventional borosilicate
waste glass. In this study, a structural model of 60P2O5-40Fe2O3 glass is
proposed. The model is based on the crystal structure of FePO4 which is composed
of [FeO4][PO4] tetrahedral rings. The rings are optimized using the DFT method
and the obtained theoretical FTIR and Raman spectra are being compared with their
experimental counterparts. Moreover, the proposed model is in very good agreement
with X-ray absorption fine structure spectroscopy (XANES/EXAFS) and Mossbauer
spectroscopy measurements. According to the calculations the Fe(3+) is in
tetrahedral and five-fold coordination. The maximal predicted load of waste
constituents into the glass without rebuilding of the structure is 30 mol%. Below
this content, waste constituents balance the charge of [FeO4](-) tetrahedra which
leads to their strong bonding to the glass resulting in an increase of the
chemical durability, transformation and melting temperatures and density.
PMID- 25115556
TI - Mast cells in a murine lung ischemia-reperfusion model of primary graft
dysfunction.
AB - Primary graft dysfunction (PGD), as characterized by pulmonary infiltrates and
high oxygen requirements shortly after reperfusion, is the major cause of early
morbidity and mortality after lung transplantation. Donor, recipient and
allograft-handling factors are thought to contribute, although new insights
regarding pathogenesis are needed to guide approaches to prevention and therapy.
Mast cells have been implicated in ischemic tissue injury in other model systems
and in allograft rejection, leading to the hypothesis that mast cell
degranulation contributes to lung injury following reperfusion injury.We tested
this hypothesis in a mouse model of PGD involving reversible disruption of blood
flow to one lung. Metrics of injury included albumin permeability, plasma
extravasation, lung histopathology, and mast cell degranulation. Responses were
assessed in wild-type (Kit+/+) and mast cell-deficient (KitW-sh/W-sh) mice.
Because mouse lungs have few mast cells compared with human lungs, we also tested
responses in mice with lung mastocytosis generated by injecting bone marrow
derived cultured mast cells (BMCMC).We found that ischemic lung responses of mast
cell-deficient KitW-sh/W-sh mice did not differ from those of Kit+/+ mice, even
after priming for injury using LPS. Degranulated mast cells were more abundant in
ischemic than in non-ischemic BMCMC-injected KitW-sh/W-sh lungs. However, lung
injury in BMCMC-injected KitW-sh/W-sh and Kit+/+ mice did not differ in globally
mast cell-deficient, uninjected KitW-sh/W-sh mice or in wild-type Kit+/+ mice
relatively deficient in lung mast cells.These findings predict that mast cells,
although activated in lungs injured by ischemia and reperfusion, are not
necessary for the development of PGD.
PMID- 25115557
TI - Acute respiratory failure in critically ill patients with interstitial lung
disease.
AB - BACKGROUND: Patients with chronic known or unknown interstitial lung disease
(ILD) may present with severe respiratory flares that require intensive
management. Outcome data in these patients are scarce. PATIENTS AND METHODS:
Clinical and radiological features were collected in 83 patients with ILD
associated acute respiratory failure (ARF). Determinants of hospital mortality
and response to corticosteroid therapy were identified by logistic regression.
RESULTS: Hospital and 1-year mortality rates were 41% and 54% respectively.
Pulmonary hypertension, computed tomography (CT) fibrosis and acute kidney injury
were independently associated with mortality (odds ratio (OR) 4.55; 95%
confidence interval (95%CI) (1.20-17.33); OR, 7.68; (1.78-33.22) and OR 10.60;
(2.25-49.97) respectively). Response to steroids was higher in patients with
shorter time from hospital admission to corticosteroid therapy. Patients with
fibrosis on CT had lower response to steroids (OR, 0.03; (0.005-0.21)). In
mechanically ventilated patients, overdistension induced by high PEEP settings
was associated with CT fibrosis and hospital mortality. CONCLUSION: Mortality is
high in ILD-associated ARF. CT and echocardiography are valuable prognostic
tools. Prompt corticosteroid therapy may improve survival.
PMID- 25115559
TI - Cotyledonary somatic embryos of Pinus pinaster Ait. most closely resemble fresh,
maturing cotyledonary zygotic embryos: biological, carbohydrate and proteomic
analyses.
AB - Cotyledonary somatic embryos (SEs) of maritime pine are routinely matured for 12
weeks before being germinated and converted to plantlets. Although regeneration
success is highly dependent on SEs quality, the date of harvesting is currently
determined mainly on the basis of morphological features. This empirical method
does not provide any accurate information about embryo quality with respect to
storage compounds (proteins, carbohydrates). We first analyzed SEs matured for
10, 12 and 14 weeks by carrying out biological (dry weight, water content) and
biochemical measurements (total protein and carbohydrate contents). No difference
could be found between collection dates, suggesting that harvesting SEs after 12
weeks is appropriate. Cotyledonary SEs were then compared to various stages, from
fresh to fully desiccated, in the development of cotyledonary zygotic embryos
(ZEs). We identified profiles that were similar using hierarchical ascendant
cluster analysis (HCA). Fresh and dehydrated ZEs could be distinguished, and SEs
clustered with fresh ZEs. Both types of embryo exhibited similar carbohydrate and
protein contents and signatures. This high level of similarity (94.5 %) was
further supported by proteome profiling. Highly expressed proteins included
storage, stress-related, late embryogenesis abundant and energy metabolism
proteins. By comparing overexpressed proteins in developing and cotyledonary SEs
or ZEs, some (23 proteins) could be identified as candidate biomarkers for the
late, cotyledonary stage. This is the first report of useful generic protein
markers for monitoring embryo development in maritime pine. Our results also
suggest that improvements of SEs quality may be achieved if the current
maturation conditions are refined.
PMID- 25115561
TI - Overgrowth of Douglas fir (Pseudotsuga menziesii Franco) stumps with regenerative
tissue as an example of cell ordering and tissue reorganization.
AB - MAIN CONCLUSION: Stump overgrowth may serve as a unique model for studying
cellular reorganization and mechanisms responsible for cell polarity changes
during the process of vascular tissue differentiation from initially unorganized
parenchymatous cells. Cellular ordering and tissue reorganization during the
overgrowth process of the transverse surfaces of Douglas fir stumps in forest
stand was studied. At the beginning of stump overgrowth, the produced
parenchymatous cells form an unorganized tissue. Particular parenchyma cells
start arranging into more ordered structures which resemble rays. Application of
digital image analysis software based on structure tensor was used. The analysis
showed that at this stage of tissue development, cellular elements display a wide
range of angular orientation values and attain very low coherency coefficients.
The progress of the tissue differentiation process is associated with the
formation of local regions with tracheids oriented circularly around the rays.
This coincides with an increase in the range of angular orientations and greater
values of coherency coefficients. At the most advanced stage of tissue
development, with tracheids arranged parallelly in longitudinal strands, the
degree of cell ordering is the highest what is manifested by the greatest values
attained by coherency coefficients, and the narrow range of angular orientations.
It is suggested that the ray-like structures could act as organizing centers in
the morphogenetic field responsible for differentiation of the overgrowth tissue.
The circular pattern of tracheids around rays in the initial phase of tissue
development can be interpreted in terms of local rotation of the morphogenetic
field which afterward is transformed into irrotational field. This transformation
is noted by the presence of tracheids arranged parallelly in longitudinal
strands. The possible involvement of a mechanism controlling cell polarity with
respect to auxin transport is discussed.
PMID- 25115560
TI - Identification and functional characterization of the distinct plant pectin
esterases PAE8 and PAE9 and their deletion mutants.
AB - MAIN CONCLUSION: PAE8 and PAE9 have pectin acetylesterase activity and together
remove one-third of the cell wall acetate associated with pectin formation in
Arabidopsis leaves. In pae8 and pae9 mutants, substantial amounts of acetate
accumulate in cell walls. In addition, the inflorescence stem height is
decreased. Pectic polysaccharides constitute a significant part of the primary
cell walls in dicotyledonous angiosperms. This diverse group of polysaccharides
has been implicated in several physiological processes including cell-to-cell
adhesion and pathogenesis. Several pectic polysaccharides contain acetyl-moieties
directly affecting their physical properties such as gelling capacity, an
important trait for the food industry. In order to gain further insight into the
biological role of pectin acetylation, a reverse genetics approach was used to
investigate the function of genes that are members of the Pectin AcetylEsterase
gene family (PAE) in Arabidopsis. Mutations in two members of the PAE family
(PAE8 and PAE9) lead to cell walls with an approximately 20 % increase in acetate
content. High-molecular-weight fractions enriched in pectic rhamnogalacturonan I
(RGI) extracted from the mutants had increased acetate content. In addition, the
pae8 mutant displayed increased acetate content also in low-molecular-weight
pectic fractions. The pae8/pae9-2 double mutant exhibited an additive effect by
increasing wall acetate content by up to 37 %, suggesting that the two genes are
not redundant and act on acetyl-substituents of different pectic domains. The
pae8 and pae8/pae9-2 mutants exhibit reduced inflorescence growth underscoring
the role of pectic acetylation in plant development. When heterologously
expressed and purified, both gene products were shown to release acetate from the
corresponding mutant pectic fractions in vitro. PAEs play a significant role in
modulating the acetylation state of pectic polymers in the wall, highlighting the
importance of apoplastic metabolism for the plant cell and plant growth.
PMID- 25115562
TI - First laccase in green algae: purification and characterization of an
extracellular phenol oxidase from Tetracystis aeria.
AB - MAIN CONCLUSION: A green algal phenol oxidase was firstly purified, confirmed to
be a laccase, and a hetero-oligomeric quaternary structure is suggested. The
operation of a laccase-mediator system is firstly described in algae. Laccases
(EC 1.10.3.2) catalyze the oxidation of a multitude of aromatic substrates. They
are well known in higher plants and fungi, while their presence in green algae
appears uncertain. Extracellular laccase-like enzyme activity has previously been
described in culture supernatants of the green soil alga Tetracystis aeria [Otto
et al. in Arch Microbiol 192:759-768, (2010)]. As reported herein, the T. aeria
enzyme was purified 120-fold by employing a combination of anion exchange and
size exclusion chromatography. The purified enzyme was confirmed to be a laccase
according to its substrate specificity. It oxidizes 2,2'-azino-bis(3
ethylbenzothiazoline-6-sulfonic acid) (ABTS), syringaldazine, and 2,6
dimethoxyphenol (pH optima of pH <= 2.5, 7.0, and 6.5; K m values of 28.8, 40.5,
and 1,830 uM; respectively), but not L-tyrosine or Fe(2+). ABTS is by far the
most efficient substrate. Two polypeptides, A (~110 kDa) and B (71 kDa), were co
purified by the applied procedure, both being highly N-glycosylated (>=~53 and >=
27 %, respectively). As suggested by various gel electrophoretic analyses, the
native enzyme (apparent molecular mass of ~220 kDa) most probably is a hetero
oligomer with the composition AB 2 , wherein A is the catalytic subunit and B
forms a disulfide-linked homo-dimer B2. The decolorization of anthraquinone (Acid
Blue 62 and Remazol Brilliant Blue R) and diazo dyes (Reactive Black 5) was
studied in the presence of redox-mediating compounds (ABTS and syringaldehyde),
demonstrating the operation of the laccase-mediator system in algae for the first
time. Thus, laccases from green algae may participate in the biotransformation of
a wide spectrum of natural and xenobiotic compounds.
PMID- 25115563
TI - Researcher Perspectives on Conflicts of Interest: A Qualitative Analysis of Views
from Academia.
AB - The increasing interconnectedness of academic research and external industry has
left research vulnerable to conflicts of interest. These conflicts have the
potential to undermine the integrity of scientific research as well as to
threaten public trust in scientific findings. The present effort sought to
identify themes in the perspectives of faculty researchers regarding conflicts of
interest. Think-aloud interview responses were qualitatively analyzed in an
effort to provide insights with regard to appropriate ways to address the threat
of conflicts of interest in research. Themes in participant responses included
disclosure of conflicts of interest, self-removal from situations where conflict
exists, accommodation of conflict, denial of the existence of conflict, and
recognition of complexity of situations involving conflicts of interest. Moral
disengagement operations are suggested to explain the appearance of each
identified theme. In addition, suggestions for best practices regarding
addressing conflicts of interest given these themes in faculty perspectives are
provided.
PMID- 25115564
TI - Technical note: a multi-dimensional description of knee laxity using radial basis
functions.
AB - The net laxity of the knee is a product of individual ligament structures that
provide constraint for multiple degrees of freedom (DOF). Clinical laxity
assessments are commonly performed along a single axis of motion, and lack
analyses of primary and coupled motions in terms of translations and rotations of
the knee. Radial basis functions (RBFs) allow multiple DOF to be incorporated
into a single method that accounts for all DOF equally. To evaluate this method,
tibiofemoral kinematics were experimentally collected from a single cadaveric
specimen during a manual laxity assessment. A radial basis function (RBF)
analysis was used to approximate new points over a uniform grid space. The
normalized root mean square errors of the approximated points were below 4% for
all DOF. This method provides a unique approach to describing joint laxity that
incorporates multiple DOF in a single model.
PMID- 25115565
TI - A new challenge: suicide attempt using nicotine fillings for electronic
cigarettes.
PMID- 25115566
TI - Probing the internal electric field in GaN/AlGaN nanowire heterostructures.
AB - We demonstrate the direct analysis of polarization-induced internal electric
fields in single GaN/Al0.3Ga0.7N nanodiscs embedded in GaN/AlN nanowire
heterostructures. Superposition of an external electric field with different
polarity results in compensation or enhancement of the quantum-confined Stark
effect in the nanodiscs. By field-dependent analysis of the low temperature
photoluminescence energy and intensity, we prove the [0001]-polarity of the
nanowires and determine the internal electric field strength to 1.5 MV/cm.
PMID- 25115567
TI - High vitamin E content, impact resistant UHMWPE blend without loss of wear
resistance.
AB - Antioxidant stabilization of radiation cross-linked ultrahigh molecular weight
polyethylene (UHMWPE) has been introduced to improve the oxidative stability of
total joint implant bearing surfaces. Blending of antioxidants (most commonly
vitamin E) with UHMWPE resin powder followed by consolidation and uniform
radiation cross-linking is currently available for use in both total hips and
total knees. It was previously shown that the fatigue resistance of vitamin E
blended and irradiated UHMWPEs could be further improved by spatially
manipulating the vitamin E concentration throughout the implant and limiting
cross-linking to the surface of the implant where it is necessary for wear
resistance. This was possible by designing a low concentration of vitamin E on
the surface and higher concentration in the bulk of the implant because cross
linking is hindered in UHMWPE as a function of increasing vitamin E
concentration. In this study, we hypothesized that such a surface cross-linked
UHMWPE with low wear rate and high fatigue strength could be obtained by limiting
the penetration of radiation into UHMWPE with uniform vitamin E concentration.
Our hypothesis tested positive; we were able to obtain control of the surface
cross-linked region by manipulating the energy of the irradiation, resulting in
extremely low wear, and high impact strength. In addition, we discussed
alternatives of improving the oxidation resistance of such a material by using
additional vitamin E reservoirs. These results are significant because this
material may allow increased use of antioxidant-stabilized, cross-linked UHMWPEs
in high stress applications and in more active patients.
PMID- 25115570
TI - Palladium-catalyzed aerobic oxidative C-H olefination with removable 1,2,3
triazole directing group.
AB - Ortho-olefination of arenes was achieved with removable 1,2,3-triazole auxiliary
through Pd-catalyzed C-H activation. Excellent yields were received even when
molecular O2 (1 atm) was used as the terminal oxidant. Other heterocyclic
directing groups, such as pyridine and quinoline, gave poor reactivity under this
aerobic oxidative condition, which highlighted the unique reactivity of triazole
in promoting directed C-H activation.
PMID- 25115568
TI - Breast bud detection: a validation study in the Chilean growth obesity cohort
study.
AB - BACKGROUND: Early puberty onset has been related to future chronic disease;
however breast bud assessment in large scale population studies is difficult
because it requires trained personnel. Thus our aim is to assess the validity of
self and maternal breast bud detection, considering girl's body mass index (BMI)
and maternal education. METHODS: In 2010, 481 girls (mean age = 7.8) from the
Growth and Obesity Chilean Cohort Study were evaluated by a nutritionist trained
in breast bud detection. In addition, the girl(n = 481) and her mother(n = 341)
classified the girl's breast development after viewing photographs of Tanner
stages. Concordance between diagnostics was estimated (kappa, Spearman
correlation) considering girls' BMI and mother's educational level. RESULTS: 14%
of the girls presented breast buds and 43% had excess weight (BMI z-score > 1,
World Health Organization 2007). Self-assessment showed low concordance with the
evaluator (K < 0.1) and girls with excess weight over-diagnosed more than girls
of normal weight (44% vs. 24%, p-value < 0.05). Instead, mothers showed good
concordance with the evaluator (K = 0.7, 95% confidence interval (CI) = 0.6-0.9),
even in overweight girls and/or in mothers with low education (K = 0.7, 95% CI =
0.6-0.8). CONCLUSIONS: Mothers were able to adequately evaluate the appearance of
breast bud despite low educational level and girls' excess weight. Mother could
be a useful resource for defining puberty onset in epidemiological studies,
particularly developing countries.
PMID- 25115571
TI - Systemic administration of 2-hydroxypropyl-beta-cyclodextrin to symptomatic Npc1
deficient mice slows cholesterol sequestration in the major organs and improves
liver function.
AB - In Niemann-Pick type C (NPC) disease, loss-of-function mutations in either NPC1
or NPC2 result in progressive accumulation of unesterified cholesterol (UC) and
glycosphingolipids in all organs, leading to neurodegeneration, pulmonary
dysfunction and sometimes liver failure. There is no cure for this disorder.
Studies using primarily NPC mouse models have shown that systemic administration
of 2-hydroxypropyl-beta-cyclodextrin (2HPbetaCD), starting in early neonatal
life, diminishes UC accumulation in most organs, slows disease progression and
extends lifespan. The key question now is whether delaying the start of 2HPbetaCD
treatment until early adulthood, when the amount of entrapped UC throughout the
body is markedly elevated, has any of the benefits found when treatment begins at
7 days of age. In the present study, Npc1(-/-) and Npc1(+/+) mice were given
saline or 2HPbetaCD subcutaneously at 49, 56, 63 and 70 days of age, with
measurements of organ weights, liver function tests and tissue cholesterol levels
performed at 77 days. In Npc1(-/-) mice, treatment with 2HPbetaCD from 49 days
reduced whole-liver cholesterol content at 77 days from 33.0 +/- 1.0 to 9.1 +/-
0.5 mg/organ. Comparable improvements were seen in other organs, such as the
spleen, and in the animal as a whole. There was a transient increase in biliary
cholesterol concentration in Npc1(-/-) mice after 2HPbetaCD. Plasma alanine
aminotransferase and aspartate aminotransferase activities in 77-day-old
2HPbetaCD-treated Npc1(-/-) mice were reduced compared with saline-treated
controls. The lifespan of Npc1(-/-) mice given 2HPbetaCD marginally exceeded that
of the saline-treated controls (99 +/- 1.1 vs 94 +/- 1.4 days, respectively; P <
0.05). Thus, 2HPbetaCD is effective in mobilizing entrapped cholesterol in late
stage NPC disease leading to improved liver function.
PMID- 25115572
TI - Combined KHFAC + DC nerve block without onset or reduced nerve conductivity after
block.
AB - OBJECTIVE: Kilohertz frequency alternating current (KHFAC) waveforms have been
shown to provide peripheral nerve conductivity block in many acute and chronic
animal models. KHFAC nerve block could be used to address multiple disorders
caused by neural over-activity, including blocking pain and spasticity. However,
one drawback of KHFAC block is a transient activation of nerve fibers during the
initiation of the nerve block, called the onset response. The objective of this
study is to evaluate the feasibility of using charge balanced direct current
(CBDC) waveforms to temporarily block motor nerve conductivity distally to the
KHFAC electrodes to mitigate the block onset-response. APPROACH: A total of eight
animals were used in this study. A set of four animals were used to assess
feasibility and reproducibility of a combined KHFAC + CBDC block. A following
randomized study, conducted on a second set of four animals, compared the onset
response resulting from KHFAC alone and combined KHFAC + CBDC waveforms. To
quantify the onset, peak forces and the force-time integral were measured during
KHFAC block initiation. Nerve conductivity was monitored throughout the study by
comparing muscle twitch forces evoked by supra-maximal stimulation proximal and
distal to the block electrodes. Each animal of the randomized study received at
least 300 s (range: 318-1563 s) of cumulative dc to investigate the impact of
combined KHFAC + CBDC on nerve viability. MAIN RESULTS: The peak onset force was
reduced significantly from 20.73 N (range: 18.6-26.5 N) with KHFAC alone to 0.45
N (range: 0.2-0.7 N) with the combined CBDC and KHFAC block waveform (p < 0.001).
The area under the force curve was reduced from 6.8 Ns (range: 3.5-21.9 Ns) to
0.54 Ns (range: 0.18-0.86 Ns) (p < 0.01). No change in nerve conductivity was
observed after application of the combined KHFAC + CBDC block relative to KHFAC
waveforms. SIGNIFICANCE: The distal application of CBDC can significantly reduce
or even completely prevent the KHFAC onset response without a change in nerve
conductivity.
PMID- 25115575
TI - Endoscopic balloon dilatation for pharyngo-upper esophageal stricture after
treatment of head and neck cancer.
AB - BACKGROUND AND AIM: Dysphagia caused by pharyngo-upper esophageal stricture is a
complication of treatment for head and neck cancer. Endoscopic balloon dilation
(EBD) is in widespread use as an effective and safe treatment for stricture in
many areas of the gastrointestinal tract. In the present study, we investigated
the efficacy and safety of EBD for pharyngo-upper esophageal strictures that
developed after treatment for head and neck cancer. METHODS: From January 2010 to
December 2013, the medical records and endoscopic findings of 19 consecutive
patients with pharyngo-upper esophageal strictures occurring after surgery and/or
chemoradiotherapy for head and neck cancer were retrospectively examined.
RESULTS: Mean number of EBD sessions per patient was 6.6 (1-30), and mean maximum
diameter of dilation was 15.8 (11-20) mm. Technical success was achieved in 16 of
19 (84.2%) patients, and only two major complications (bleeding and pha ryngeal
edema) occurred in a total of 125 dilatation sessions (1.6%). Regarding the
influence of chemoradiotherapy on the outcome of EBD, patients who had undergone
chemoradiotherapy plus surgery experienced significantly more restenosis during
the follow-up period compared to those who had undergone surgery alone (50% vs
0%, P < 0.05). CONCLUSIONS: This retrospective analysis demonstrated the efficacy
and safety of exclusive EBD for pharyngo-upper esophageal strictures occurring
after treatment for head and neck cancer, indicating that the therapeutic
application of EBD could be extended to such strictures. Patients who underwent
chemoradiotherapy and surgery experienced more restenosis; hence, such patients
should be carefully followed up after EBD treatment.
PMID- 25115576
TI - Invited commentary on the paper entitled 'methicillin-resistant Staphylococcus
aureus infection: an independent risk factor for mortality in patients with
poststernotomy mediastinitis'.
PMID- 25115577
TI - Prevalence of musculoskeletal pain in a sample of migrant workers in the
manufacturing industry in Malaysia.
PMID- 25115580
TI - The brief cognitive assessment tool (BCAT): cross-validation in a community
dwelling older adult sample.
AB - ABSTRACT Background: Cognitive impairment is underrecognized and misdiagnosed
among community-dwelling older adults. At present, there is no consensus about
which cognitive screening tool represents the "gold standard." However, one tool
that shows promise is the Brief Cognitive Assessment Tool (BCAT), which was
originally validated in an assisted living sample and contains a multi-level
memory component (e.g. word lists and story recall items) and complex executive
functions features (e.g. judgment, set-shifting, and problem-solving). Methods:
The present study cross-validated the BCAT in a sample of 75 community-dwelling
older adults. Participants completed a short battery of several individually
administered cognitive tests, including the BCAT and the Montreal Cognitive
Assessment (MoCA). Using a very conservative MoCA cut score of <26, the base rate
of cognitive impairment in this sample was 35%. Results: Adequate internal
consistency and strong evidence of construct validity were found. A receiver
operating characteristic (ROC) curve was calculated from sensitivity and 1
specificity values for the classification of cognitively impaired versus
cognitively unimpaired. The area under the ROC curve (AUC) for the BCAT was .90,
p < 0.001, 95% CI [0.83, 0.97]. A BCAT cut-score of 45 (scores below 45
suggesting cognitive impairment) resulted in the best balance between sensitivity
(0.81) and specificity (0.80). Conclusions: A BCAT cut-score can be used for
identifying persons to be referred to appropriate healthcare professionals for
more comprehensive cognitive assessment. In addition, guidelines are provided for
clinicians to interpret separate BCAT memory and executive dysfunction component
scores.
PMID- 25115579
TI - Sustained release of 17beta-estradiol stimulates osteogenic differentiation of
adipose tissue-derived mesenchymal stem cells on chitosan-hydroxyapatite
scaffolds.
AB - The aim of this study was to develop a 17beta-estradiol (E2)-releasing scaffold
nanoparticle system in order to promote osteogenic differentiation of rat adipose
tissue-derived mesenchymal stem cells (AdMSCs) for bone tissue regeneration. E2
loaded poly(lactide-co-glycolide) (PLGA) nanoparticles with a diameter of ~240 nm
were produced via an emulsion-diffusion-evaporation method. Because of its higher
encapsulation efficiency (54%), PLGA, which has a 65:35 composition, was chosen
for the preparation of nanoparticles. Chitosan-hydroxyapatite (HA) scaffolds in
macroporous structures with interconnected pores were prepared by combining
microwave irradiation and gas-foaming techniques. PLGA nanoparticles were loaded
onto scaffolds in 2 ways: via embedding after scaffold fabrication and during
fabrication. While 100% of the loaded E2 was released during 55 days from
scaffolds loaded by embedding, a controlled release behavior of E2 was observed
over 135 days in scaffolds loaded during manufacture. The results of cell culture
studies indicated that the controlled delivery of E2 from PLGA nanoparticles
loaded on chitosan-HA scaffolds had a significant effect on the osteogenic
differentiation of AdMSCs.
PMID- 25115578
TI - Antiadhesive activity of poly-hydroxy butyrate biopolymer from a marine
Brevibacterium casei MSI04 against shrimp pathogenic vibrios.
AB - BACKGROUND: Vibrio pathogens are causative agents of mid-culture outbreaks, and
early mortality syndrome and secondary aetiology of most dreadful viral outbreaks
in shrimp aquaculture. Among the pathogenic vibrios group, Vibrio alginolyticus
and V. harveyi are considered as the most significant ones in the grow-out ponds
of giant black tiger shrimp Penaeus monodon in India. Use of antibiotics was
banned in many countries due to the emergence of antibiotic-resistant strains and
accumulation of residual antibiotics in harvested shrimp. There is an urgent need
to consider the use of alternative antibiotics for the control of vibriosis in
shrimp aquaculture. Biofilm formation is a pathogenic and/or establishment
mechanism of Vibrio spp. This study aims to develop novel safe antibiofilm and/or
antiadhesive process using PHB to contain vibrios outbreaks in shrimp
aquaculture. RESULTS: In this study a poly-hydroxy butyrate (PHB) polymer
producing bacterium Brevibacterium casei MSI04 was isolated from a marine sponge
Dendrilla nigra and production of PHB was optimized under submerged-fermentation
(SmF) conditions. The effect of carbon, nitrogen and mineral sources on PHB
production and enhanced production of PHB by response surface methods were
demonstrated. The maximum PHB accumulation obtained was 6.74 g/L in the optimized
media containing 25 g/L starch as carbon source, 96 h of incubation, 35 degrees C
and 3% NaCl. The highest antiadhesive activity upto 96% was recorded against V.
vulnificus, and V. fischeri, followed by 92% against V. parahaemolyticus and V.
alginolyticus and 88% inhibition was recorded against V. harveyi. CONCLUSION: In
this study, a thermostable biopolymer was chemically characterized as PHB based
on 1HNMR spectra, FT-IR and GC-MS spectra. The NMR spectra revealed that the
polymer was an isocratic homopolymer and it also confirmed that the compound was
PHB. The antiadhesive activity of PHB was determined in microtitre plate assay
and an effective concentration (EC) of PHB (200 MUl containing 0.6 mg PHB) was
confirmed by confocal laser scanning microscopic analysis of vibrio biofilm on
pre-treated glass and polystyrene surfaces. This is a first report on anti
adhesive activity of PHB against prominent vibrio pathogens in shrimp
aquaculture.
PMID- 25115581
TI - Designing mixed metal halide ammines for ammonia storage using density functional
theory and genetic algorithms.
AB - Metal halide ammines have great potential as a future, high-density energy
carrier in vehicles. So far known materials, e.g. Mg(NH3)6Cl2 and Sr(NH3)8Cl2,
are not suitable for automotive, fuel cell applications, because the release of
ammonia is a multi-step reaction, requiring too much heat to be supplied, making
the total efficiency lower. Here, we apply density functional theory (DFT)
calculations to predict new mixed metal halide ammines with improved storage
capacities and the ability to release the stored ammonia in one step, at
temperatures suitable for system integration with polymer electrolyte membrane
fuel cells (PEMFC). We use genetic algorithms (GAs) to search for materials
containing up to three different metals (alkaline-earth, 3d and 4d) and two
different halides (Cl, Br and I) - almost 27,000 combinations, and have
identified novel mixtures, with significantly improved storage capacities. The
size of the search space and the chosen fitness function make it possible to
verify that the found candidates are the best possible candidates in the search
space, proving that the GA implementation is ideal for this kind of computational
materials design, requiring calculations on less than two percent of the
candidates to identify the global optimum.
PMID- 25115582
TI - Histologic analysis of the hernia sac: current practices based on a survey of
IPEG members.
AB - INTRODUCTION: Inguinal hernia repair is one of the most common operations
performed by pediatric surgeons. Although the practice of sending the hernia sac
for histologic examination after routine hernia repair is common, the indications
and practice patterns for this have not been evaluated. The objective of this
survey was to determine practice patterns and indications for histologic analysis
of the pediatric inguinal hernia sac. MATERIALS AND METHODS: A 9-question online
survey was sent to all members of the International Pediatric Endosurgery Group
(IPEG). A Kruskal-Wallis test was used to determine whether practice patterns of
sending the hernia sac for histologic evaluation were associated with respondent
characteristics. The chi-squared test with Yates's correction was used where
appropriate. RESULTS: The survey was completed by 315 IPEG members, for a
response rate of 54.4%. Hernia sacs were sent for histologic evaluation always by
23.9%, often by 5.1%, rarely by 17.5%, and never by 53.5%. The respondent
characteristics were not associated with whether or not specimens were sent for
histology review. Of the 128 who reported sending the inguinal hernia sac, the
most common reasons were hospital/state requirements (47.6%), followed by routine
practice (25.7%) and concern for missed pathology (24.2%). CONCLUSIONS: The
majority of IPEG respondents report never sending the inguinal hernia sac for
histologic analysis. Of those that do, most are influenced by hospital/state
requirements. The value of sending the hernia sac after routine inguinal hernia
repair should be validated if it is to remain an institutional requirement.
PMID- 25115583
TI - What are the results using the modified trapdoor procedure to treat
chondroblastoma of the femoral head?
AB - BACKGROUND: Treatment of chondroblastoma in the femoral head is challenging owing
to the particular location and its aggressive nature. There is little published
information to guide the surgeon regarding the appropriate approach to treating a
chondroblastoma in this location. We developed a modified trapdoor procedure to
address this issue. The primary modification is that the window surface of the
femoral head is covered by the ligamentum teres rather than cartilage as in the
traditional procedure. QUESTIONS/PURPOSES: We assessed (1) the clinical
presentation of chondroblastoma of the femoral head and treatment results with
the modified trapdoor procedure in terms of (2) the frequency of local
recurrence, (3) complications, and (4) functional outcomes using the
Musculoskeletal Tumor Society (MSTS) score. METHODS: Between 1999 and 2010, we
treated 14 patients for chondroblastoma of the femoral head. All patients
received the modified trapdoor procedure. Of those, 13 were available for
followup at a minimum of 36 months (mean, 66 months; range, 36-117 months) and
one patient was lost to followup. There were nine males and four females, with a
mean age of 18 years (range, 9-29 years). Clinical features were ascertained by
chart and radiographic review, and recurrence, complications, and functional
outcomes (MSTS score) were recorded from chart review. Patterns of bone
destruction were evaluated using the Lodwick classification, which ranges from IA
(geographic appearance with sclerotic rim) to III (permeative appearance).
RESULTS: The symptoms at diagnosis were pain in nine patients and discomfort in
four. The mean duration of symptom was 11 months (range, 1-36 months). The physis
was open in two patients, closing in one, and closed in 10. The patterns of bone
destruction were evaluated as Lodwick Class IA in six patients, Lodwick Class IB
in five, and Lodwick Class IC in two. At latest followup, no local recurrence was
observed. Two patients had postoperative complications. One had avascular
necrosis of the femoral head and was treated with prosthesis replacement. The
other had asymptomatic heterotopic ossification in the surgical field. The mean
MSTS score was 29.6 (range, 28-30). CONCLUSIONS: Based on this small series, we
believe our modified trapdoor procedure is a safe, effective means of treating a
chondroblastoma in the femoral head, but additional clinical evaluation with more
patients is necessary to confirm our findings. LEVEL OF EVIDENCE: Level IV,
therapeutic study. See the Instructions for Authors for a complete description of
levels of evidence.
PMID- 25115584
TI - How does ulnar shortening osteotomy influence morphologic changes in the
triangular fibrocartilage complex?
AB - BACKGROUND: Ulnar shortening osteotomy often is indicated for treatment of
injuries to the triangular fibrocartilage complex (TFCC). However, the effect of
ulnar shortening osteotomy on the changes in shape of the TFCC is unclear. In our
study, quantitative evaluations were performed using MRI to clarify the effect of
ulnar shortening on triangular fibrocartilage (TFC) thickness attributable to
disc regeneration of the TFC and TFC angle attributable to the suspension effect
of ulnar shortening on the TFC. QUESTIONS/PURPOSES: The purposes of this study
were (1) to compare preoperative and postoperative TFC thickness and TFC angle on
MR images to quantitatively evaluate the effect of ulnar shortening osteotomy on
disc regeneration and the suspension effect on the TFC; and (2) to assess whether
changes in TFC thickness and TFC angle correlated with the Mayo wrist score.
METHODS: Between 1995 and 2008, 256 patients underwent ulnar shortening osteotomy
for TFCC injuries. The minimum followup was 24 months (mean, 51 months; range, 24
210 months). A total of 79 patients (31%) with complete followup including
preoperative and postoperative MR images and the Mayo wrist score was included in
this retrospective study. Evaluation of the postoperative MR images and the Mayo
wrist score were performed at the final followup. The remaining 177 patients did
not undergo postoperative MRI, or they had a previous fracture, large tears of
the disc proper, or were lost to followup. Two orthopaedists, one of whom
performed the surgeries, measured the TFC thickness and the TFC angle on coronal
MR images before and after surgery for each patient. Correlations of the percent
change in the TFC thickness and the magnitude of TFC angle change with age, sex,
postoperative MR images, extent of ulnar shortening, preoperative ulnar variance,
and postoperative Mayo wrist score were assessed. RESULTS: Stepwise regression
analysis showed a correlation between the percent change in TFC thickness and
preoperative ulnar variance (R2=0.21; beta=-0.33; 95% CI, -0.11 to 0.01; p=0.01)
and between the magnitude of change in the TFC angle and the extent of ulnar
shortening (R2=0.18; beta=-0.29; 95% CI, -5.8 to 0.29; p=0.03). The Mayo wrist
score was not correlated with the percent change in TFC thickness or the
magnitude of change in the TFC angle. CONCLUSIONS: These results suggest that, in
patients with TFCC injury with a smaller preoperative ulnar variance, a high
residual potential for regeneration in the disc proper was seen after ulnar
shortening osteotomy, and correlated with the extent of ulnar shortening and the
suspension effect on TFC. However, there was no correlation between disc
regeneration or the suspension effect on TFC and the Mayo wrist score. LEVEL OF
EVIDENCE: Level IV, therapeutic study. See the Instructions for Authors for a
complete description of levels of evidence.
PMID- 25115586
TI - Letter to the editor: editorial: transition from training to practice--is there a
better way?
PMID- 25115585
TI - Highly crosslinked polyethylene improves wear but not surface damage in retrieved
acetabular liners.
AB - BACKGROUND: Highly crosslinked polyethylene (XLPE) is believed to demonstrate
better wear resistance than conventional polyethylene (CPE) in total hip
arthroplasty. QUESTIONS/PURPOSES: The purpose of this study was to compare visual
damage scores and micro-CT measurements of penetration, a surrogate for wear,
between matched retrieved XLPE and CPE acetabular liners. METHODS: Thirteen XLPE
acetabular liners were matched in terms of implant design (all were of the same
design), patient age, sex, liner dimensions, duration of implantation, and reason
for revision to a group of CPE liners that were retrieved in the same time
period. Penetration resulting from the combination of wear and creep in the two
groups of liners was measured with micro-CT. Surface damage was scored by two
blinded observers using a surface damage system that considers the seven common
damage modes: pitting, scratching, burnishing, abrasions, impingement, embedded
debris, and delamination, and wear patterns were documented. RESULTS: There was
no difference (p=0.32) in total damage score between the XLPE group (14+/-4) and
the CPE group (15+/-5). However, there was three times greater penetration (odds
ratio, 3.1; confidence interval, 2.3-5.1; p<0.001) in the CPE group (0.18+/-0.09
mm/year) than in the XLPE group (0.05+/-0.07 mm/year). There was less volumetric
loss in XLPE (82+/-SD 134 mm3) versus the CPE group (350+/-SD 342 mm3; p=0.017).
CONCLUSIONS: XLPE liners undergo less penetration as a result of creep and wear
than CPE liners based on quantitative measurements provided by micro-CT, which
was not apparent using damage scoring alone. This demonstrates the use of three
dimensional imaging techniques such as micro-CT for quantifying wear in retrieval
studies. CLINICAL RELEVANCE: In this study, XLPE had less wear but similar damage
scores than CPE, allaying concerns that the beneficial wear properties of XLPE
might come with a tradeoff arising from the increased brittleness of that
material.
PMID- 25115588
TI - CORR Insights(r): the Otto Aufranc Award: modifiable versus nonmodifiable risk
factors for infection after hip arthroplasty.
PMID- 25115587
TI - Collateral ligament laxity in knees: what is normal?
AB - BACKGROUND: Proper alignment and balancing of soft tissues of the knee are
important goals for TKA. Despite standardized techniques, there is no consensus
regarding the optimum amount of collateral ligament laxity one should leave at
the end of the TKA. QUESTIONS/PURPOSES: I asked (1) what is the collateral laxity
in young healthy volunteers, and (2) is there a difference in collateral laxity
between males and females. METHODS: The femorotibial mechanical angle (FTMA) was
measured in 314 knees in healthy volunteers aged 19 to 35 years. Subjects with a
history of pain, malalignment, dysplasia, or trauma were excluded. Twenty-five
knees were excluded because the hip center could not be acquired, and 22 were
excluded because of a history of pain and trauma, leaving 267 knees for inclusion
in the study. Of these, 155 were from men and 112 were from women. A validated
method using a computer navigation system was used to obtain the measurements. A
10-Nm torque was used to stress the knee in varus and valgus at 0 degrees
extension and 15 degrees flexion. An independent t-test and ANOVA were applied
to the data to calculate any significant difference between groups (p<0.05).
RESULTS: The mean (SD) unstressed supine FTMA was varus of 1.2 degrees (SD, 4
degrees ) in 0 degrees extension and varus of 1.2 degrees (SD, 4.4 degrees ) in
15 degrees flexion (p=0.88). On varus torque of 10 Nm, the supine FTMA changed
by a mean of 3.1 degrees (SD, 2 degrees ) (95% CI, 2.4 degrees -3.8 degrees ;
p<0.001) in 0 degrees extension and 6.9 degrees (SD, 2.6 degrees ) (95% CI, 6.2
degrees -7.7 degrees ; p<0.001) in 15 degrees flexion. On valgus torque of 10
Nm, the FTMA changed by a mean of 4.6 degrees (SD, 2.2 degrees ) (95% CI, 3.9
degrees -5.3 degrees ; p<0.001) in 0 degrees extension and 7.9 degrees (SD, 3.4
degrees ) (95% CI, 7.1 degrees -8.7 degrees ; p<0.001) in 15 degrees flexion.
The mean unstressed FTMA in 0 degrees extension was varus of 1.7 degrees (SD, 4
degrees ) in men and 0.4 degrees (SD, 3.9 degrees ) in women (p=0.01).
Differences in collateral ligament laxity were seen between men and women
(p<0.001 for valgus torque and 0.035 for varus torque in 15 degrees flexion).
With valgus torque at 0 degrees flexion, the supine FTMA change was valgus of
4.2 degrees (SD, 2.0 degrees ) for men and 5.0 degrees (SD, 2.4 degrees ) for
women, while at 15 degrees flexion the FTMA change was valgus 7.6 degrees (SD,
3.6 degrees ) for men and 8.3 degrees (SD, 3.2 degrees ) for women With varus
torque at 0 degrees flexion, additional varus was -3.0 degrees (SD, 1.8 degrees
) for men and -3.3 degrees (SD, 2.2 degrees ) for women, while at 15 degrees
flexion, varus was -7.0 degrees SD, (2.5 degrees ) for men and -6.9 degrees
(SD, 2.8 degrees ) for women. CONCLUSIONS: The collateral laxity in young healthy
volunteers was quantified in this study. The collateral ligament laxity is
variable in different persons. In addition, ligaments in women are more lax than
in men in valgus stress. CLINICAL RELEVANCE: This study was conducted on young,
healthy knees. Whether the findings are applicable to arthritic knees and
replaced knees needs additional evaluation. However the findings provide a
baseline from which to work in the evaluation of arthritic knees and in the case
of TKA.
PMID- 25115589
TI - Has the incidence of thoracolumbar spine injuries increased in the United States
from 1998 to 2011?
AB - BACKGROUND: While most motor vehicle crash (MVC)-related injuries have been
decreasing, one study showed increases in MVC-related spinal fractures from 1994
to 2002 in Wisconsin. To our knowledge, no studies evaluating nationwide trends
of MVC-related thoracolumbar spine injuries have been published. Such fractures
can cause pain, loss of functionality or even death. If the incidence of such
injuries is increasing, it may provide a motive for reassessment of current
vehicle safety design. QUESTIONS/PURPOSES: We questioned whether the incidence of
thoracolumbar spine injuries increased in the United States population with time
(between 1998 and 2011), and if there was an increased incidence of thoracolumbar
injuries, whether there were identifiable compensatory "trade-off injury"
patterns, such as reductions in sacropelvic injuries. PATIENTS AND METHODS:
Institutional review board approval was obtained for retrospective review of
three national databases: the National Trauma Databank(r) (NTDB(r)), 2002-2006,
National Automotive Sampling System (NASS), 2000-2011, and National Inpatient
Sample (NIS), 1998-2007. In each database, the total number of MVC-related
injuries and the number of MVC-related thoracolumbar injuries per year were
identified using appropriate Abbreviated Injury Scale (AIS) or ICD-9 codes.
Sacropelvic injuries also were identified to evaluate their potential as trade
off injuries. Poisson regression models adjusting for age were used to analyze
trends in the data with time. RESULTS: All databases showed increases in MVC
related thoracolumbar spine injuries when adjusting for age with time. These age
adjusted relative annual percent increases ranged from 8.22% (95% CI, 5.77%
10.72%; p<0.001) using AIS of 2 or more (AIS2 +) injury codes in the NTDB(r),
8.59% (95% CI, 5.88%-11.37%; p<0.001) using ICD-9 codes in the NTDB(r), 8.12%
(95% CI, 7.20%-9.06%; p<0.001) using ICD-9 codes in the NIS, and 8.10 % (95% CI
5.00%-11.28%; p<0.001) using AIS2+ injury codes in the NASS. As these
thoracolumbar injuries have increased, there has been no consistent trend toward
a compensatory reduction in terms of sacropelvic injuries. CONCLUSIONS: While
other studies have shown that rates of many MVC-related injuries are declining
with time, our data show increases in the incidence of thoracolumbar injury.
Although more sensitive screening tools likely have resulted in earlier and
increased recognition of these injuries, it cannot be stated for certain that
this is the only driver of the increased incidence observed in this study. As
seatbelt use has continued to increase, this trend may be the result of
thoracolumbar injuries as trade-offs for other injuries, although in our study we
did not see a compensatory decrease in sacropelvic injuries. Investigation
evaluating the root of this pattern is warranted.
PMID- 25115590
TI - SARP19 and vdg3 gene families are functionally related during abalone
metamorphosis.
AB - The transcriptional activity of the SARP19-I1 and vdg3-I1 genes increases over
tenfold when Haliotis diversicolor larvae shift from the pelagic to benthic
lifestyle, signifying the important role of these genes during abalone
metamorphosis. In this study, eight paralogous SARP19 genes and six paralogous
vdg3 genes were identified from H. diversicolor transcriptomes. Phylogenetic
analyses were performed, and the spatio-temporal expression patterns of these
genes were separately determined by quantitative polymerase chain reaction (qPCR)
and whole mount in situ hybridization (WMISH). Five SARP19 paralogs and five vdg3
paralogs showed at least a tenfold increase in expression after settlement. Among
these differentially expressed genes, three SARP19 paralogs and four vdg3
paralogs were verified as being spatially expressed in the digestive glands of
newly settled postlarvae. We proposed that a hypothesis of coevolution between
the two gene families might explain the similarities in their expression patterns
and their phylogenetics.
PMID- 25115592
TI - Looking into meta-atoms of plasmonic nanowire metamaterial.
AB - Nanowire-based plasmonic metamaterials exhibit many intriguing properties related
to the hyperbolic dispersion, negative refraction, epsilon-near-zero behavior,
strong Purcell effect, and nonlinearities. We have experimentally and numerically
studied the electromagnetic modes of individual nanowires (meta-atoms) forming
the metamaterial. High-resolution, scattering-type near-field optical microscopy
has been used to visualize the intensity and phase of the modes. Numerical and
analytical modeling of the mode structure is in agreement with the experimental
observations and indicates the presence of the nonlocal response associated with
cylindrical surface plasmons of nanowires.
PMID- 25115591
TI - Antagonistic role of CotG and CotH on spore germination and coat formation in
Bacillus subtilis.
AB - Spore formers are bacteria able to survive harsh environmental conditions by
differentiating a specialized, highly resistant spore. In Bacillus subtilis, the
model system for spore formers, the recently discovered crust and the
proteinaceous coat are the external layers that surround the spore and contribute
to its survival. The coat is formed by about seventy different proteins assembled
and organized into three layers by the action of a subset of regulatory proteins,
referred to as morphogenetic factors. CotH is a morphogenetic factor needed for
the development of spores able to germinate efficiently and involved in the
assembly of nine outer coat proteins, including CotG. Here we report that CotG
has negative effects on spore germination and on the assembly of at least three
outer coat proteins. Such negative action is exerted only in mutants lacking
CotH, thus suggesting an antagonistic effect of the two proteins, with CotH
counteracting the negative role of CotG.
PMID- 25115593
TI - Gross Morphometric Studies on the Tongue, Buccal Cavity and Hard Palate of the
Fruit Bat (Eidolon helvum).
AB - This study was designed to assess the gross morphometric studies of the tongue,
hard palate and buccal cavity of the fruit bat (Eidolon helvum). Sixty bats of
both sexes were used for this study. The tongue was excised, and the weight and
various linear measurements were determined. Linear measurements were also
determined on the hard palate. The gross distribution of the lingual papillae was
observed to be the same in both sexes; values obtained for the weight and length
of the tongue were higher in the females, although no statistically significant
differences were observed (P > 0.05). The number of ridges on the hard palate
displayed sexual dimorphism. Results obtained from this study may find
application in the field of comparative and clinical anatomy of wildlife and also
in feeding physiology.
PMID- 25115594
TI - Biocompatibility and efficacy of collagen/gelatin sponge scaffold with sustained
release of basic fibroblast growth factor on vocal fold fibroblasts in 3
dimensional culture.
AB - OBJECTIVE: Treatment of vocal fold scarring remains challenging. We have
previously reported the therapeutic effects of local injection of basic
fibroblast growth factor (bFGF) in animal models and humans. A novel
collagen/gelatin sponge (CGS) is capable of sustained release of bFGF, which
compensates for its quick absorption in vivo, avoiding multiple injections. This
study aimed to evaluate the biocompatibility and efficacy of the CGS in rat vocal
fold fibroblasts prior to human trials. METHODS: Fibroblasts extracted from
Sprague-Dawley rat vocal folds were seeded onto a CGS and then cultivated with
bFGF at concentrations of 0, 10, and 100 ng/mL. Vocal fold fibroblast morphology,
adhesion, proliferation, and gene expression were measured under these 3
dimensional conditions. RESULTS: Cells adhered to the CGS from day 1. Although no
significant differences in cell morphology were detected, cell proliferation was
accelerated by bFGF administration. Expression of endogenous bFGF and hepatocyte
growth factor was significantly up-regulated at 10 ng/mL bFGF. The expression of
procollagen I and procollagen III was significantly suppressed, whereas HAS-1 and
HAS-2 were up-regulated at 10 and 100 ng/mL bFGF. CONCLUSION: The
collagen/gelatin sponge is biocompatible with vocal fold fibroblasts and may be
useful as a bFGF drug delivery system for the treatment of scarred vocal folds.
PMID- 25115595
TI - Reinforcer magnitude and rate dependency: evaluation of resistance-to-change
mechanisms.
AB - Under many circumstances, reinforcer magnitude appears to modulate the rate
dependent effects of drugs such that when schedules arrange for relatively larger
reinforcer magnitudes rate dependency is attenuated compared with behavior
maintained by smaller magnitudes. The current literature on resistance to change
suggests that increased reinforcer density strengthens operant behavior, and such
strengthening effects appear to extend to the temporal control of behavior. As
rate dependency may be understood as a loss of temporal control, the effects of
reinforcer magnitude on rate dependency may be due to increased resistance to
disruption of temporally controlled behavior. In the present experiments, pigeons
earned different magnitudes of grain during signaled components of a multiple FI
schedule. Three drugs, clonidine, haloperidol, and morphine, were examined. All
three decreased overall rates of key pecking; however, only the effects of
clonidine were attenuated as reinforcer magnitude increased. An analysis of
within-interval performance found rate-dependent effects for clonidine and
morphine; however, these effects were not modulated by reinforcer magnitude. In
addition, we included prefeeding and extinction conditions, standard tests used
to measure resistance to change. In general, rate-decreasing effects of
prefeeding and extinction were attenuated by increasing reinforcer magnitudes.
Rate-dependent analyses of prefeeding showed rate-dependency following those
tests, but in no case were these effects modulated by reinforcer magnitude. The
results suggest that a resistance-to-change interpretation of the effects of
reinforcer magnitude on rate dependency is not viable.
PMID- 25115596
TI - Effects of Withania somnifera on oral ethanol self-administration in rats.
AB - Recent evidence has shown that Withania somnifera Dunal (Ashwagandha or Indian
ginseng), a herbal remedy used in traditional medicine, impairs morphine-elicited
place conditioning. Here, we investigated the effect of W. somnifera roots
extract (WSE) on motivation for drinking ethanol using operant self
administration paradigms. Wistar rats were trained to self-administer ethanol
(10%) by nose-poking. The effects of WSE (25-75 mg/kg) were evaluated on
acquisition and maintenance, on ethanol breakpoint under a progressive-ratio
schedule of reinforcement and on the deprivation effect and reinstatement of
seeking behaviours. Moreover, on the basis of the recent suggestion of an
involvement of GABAB receptors in WSE central effects, we studied the interaction
between WSE and GABAB ligands. The effect of WSE on saccharin (0.05%) oral self
administration was also tested. The results show that WSE reduced the
acquisition, maintenance and breakpoint of ethanol self-administration. WSE also
reduced the deprivation effect, reinstatement of ethanol-seeking behaviours and
saccharin reinforcement. Furthermore, the GABAB receptor antagonist, phaclofen,
counteracted the ability of WSE to impair the maintenance of ethanol self
administration. These findings show that WSE, by an action that may involve GABAB
receptors, impairs motivation for drinking ethanol and suggest that further
investigations should be performed to determine whether W. somnifera may
represent a new approach for the management of alcohol abuse.
PMID- 25115597
TI - Improving primary care through information. A Wonca keynote paper.
AB - Information from health care encounters across the entire health care spectrum,
when consistently collected, analysed and applied can provide a clearer picture
of patients' history as well as current and future needs through a better
understanding of their morbidity burden and health care experiences. It can
facilitate clinical activity to target limited resources to those patients most
in need through risk adjustment mechanisms that consider the morbidity burden of
populations, and it can help target quality improvement and cost saving
activities in the right places. It can also open the door to a new chapter of
evidence-based medicine around multi-morbidity. In summary, it can support a
better integrated health system where primary care can provide continuous,
coordinated, and comprehensive person-centred care to those who could benefit
most. This paper explores the potential uses of information collected in
electronic health records (EHRs) to inform case-mix and predictive modelling, as
well as the associated challenges, with a particular focus on their application
to primary care.
PMID- 25115598
TI - A mini review on renewable sources for biofuel.
AB - Rapid growth in both global energy demand and carbon dioxide emissions associated
with the use of fossil fuels has driven the search for alternative sources which
are renewable and have a lower environmental impact. This paper reviews the
availability and bioenergy potentials of the current biomass feedstocks. These
include (i) food crops such as sugarcane, corn and vegetable oils, classified as
the first generation feedstocks, and (ii) lignocellulosic biomass derived from
agricultural and forestry residues and municipal waste, as second generation
feedstocks. The environmental and socioeconomic limitations of the first
generation feedstocks have placed greater emphasis on the lignocellulosic
biomass, of which the conversion technologies still faces major constraints to
full commercial deployment. Key technical challenges and opportunities of the
lignocellulosic biomass-to-bioenergy production are discussed in comparison with
the first generation technologies. The potential of the emerging third generation
biofuel from algal biomass is also reviewed.
PMID- 25115599
TI - Aerobic direct C-H arylation of nonbiased olefins.
AB - An efficient ligand-promoted biomimetic aerobic oxidative dehydrogenative cross
coupling between arenes and nonbiased olefins is presented. Acridine as a ligand
was found to significantly enhance the rate, the yield, and the scope of the
reaction under ambient oxygen pressure, providing a variety of alkenylarenes via
an environmentally friendly procedure.
PMID- 25115604
TI - Drivers influencing streamflow changes in the Upper Turia basin, Spain.
AB - Many rivers across the world have experienced a significant streamflow reduction
over the last decades. Drivers of the observed streamflow changes are multiple,
including climate change (CC), land use and land cover changes (LULCC), water
transfers and river impoundment. Many of these drivers inter-act simultaneously,
making it difficult to discern the impact of each driver individually. In this
study we isolate the effects of LULCC on the observed streamflow reduction in the
Upper Turia basin (east Spain) during the period 1973-2008. Regression models of
annual streamflow are fitted with climatic variables and also additional time
variant drivers like LULCC. The ecohydrological model SWAT is used to study the
magnitude and sign of streamflow change when LULCC occurs. Our results show that
LULCC does play a significant role on the water balance, but it is not the main
driver underpinning the observed reduction on Turia's streamflow. Increasing mean
temperature is the main factor supporting increasing evapotranspiration and
streamflow reduction. In fact, LULCC and CC have had an offsetting effect on the
streamflow generation during the study period. While streamflow has been
negatively affected by increasing temperature, ongoing LULCC have positively
compensated with reduced evapotranspiration rates, thanks to mainly shrubland
clearing and forest degradation processes. These findings are valuable for the
management of the Turia river basin, as well as a useful approach for the
determination of the weight of LULCC on the hydrological response in other
regions.
PMID- 25115606
TI - Mercury biogeochemical cycling and processes: implications for human and
ecosystem health.
PMID- 25115608
TI - Shrinkage assessment of low shrinkage composites using micro-computed tomography.
AB - OBJECTIVES: The aim of this study was to quantify the polymerization volumetric
shrinkage of one regular and two low shrinkage bulk fill composites in class I
cavities with or without an adhesive layer, using three-dimensional (3D) micro
computed tomography (MUCT). METHODS: Class I cavity preparations (2.5 mm depth *
4 mm length * 4 mm wide) were standardized in 36 extracted human third molars,
which were randomly divided in six groups (n = 6 each) as follows: Group VIT
(regular composite without bonding agent); Group SDR (low shrinkage flowable
composite without bonding agent); Group TET (low shrinkage composite without
bonding agent); Group VIT/P (regular composite with bonding agent); Group SDR/X
(low shrinkage flowable composite with bonding agent); TET/T (low shrinkage
composite with bonding agent). Each tooth was scanned via uCT at cavity
preparation, immediately after cavity filling, and after light-curing. Acquired
MUCT data were imported into Amira software for analysis and volume values
evaluated between steps from cavity preparation until light-curing. RESULTS: Both
low shrinkage composites showed a significantly less volumetric shrinkage than
VIT. The use of dental adhesive significantly decreased the average volumetric
contraction similarly for the three composites, by about 20%. CONCLUSION: Both
low shrinkage composites showed less volumetric polymerization contraction than
the regular composite. The use of dental adhesive decreased the total volumetric
shrinkage for all evaluated composites.
PMID- 25115605
TI - Predictors of serum polychlorinated biphenyl concentrations in Anniston
residents.
AB - The Anniston Community Health Survey was a community-based cross-sectional study
of Anniston, Alabama, residents who live in close proximity to a former PCB
production facility to identify factors associated with serum PCB levels. The
survey comprises 765 Anniston residents who completed a questionnaire interview
and provided a blood sample for analysis in 2005-2007. Several reports based on
data from the Anniston survey have been previously published, including
associations between PCB exposure and diabetes and blood pressure. In this study
we examine demographic, behavioral, dietary, and occupational characteristics of
Anniston survey participants as predictors of serum PCB concentrations. Of the
765 participants, 54% were White and 45% were African-American; the sample was
predominantly female (70%), with a mean age of 55 years. Serum PCB concentrations
varied widely between participants (range for sum of 35 PCBs: 0.11-170.4 ng/g wet
weight). Linear regression models with stepwise selection were employed to
examine factors associated with serum PCBs. Statistically significant positive
associations were observed between serum PCB concentrations and age, race,
residential variables, current smoking, and local fish consumption, as was a
negative association with education level. Age and race were the most influential
predictors of serum PCB levels. A small age by sex interaction was noted,
indicating that the increase in PCB levels with age was steeper for women than
for men. Significant interaction terms indicated that the associations between
PCB levels and having ever eaten locally raised livestock and local clay were
much stronger among African-Americans than among White participants. In summary,
demographic variables and past consumption of locally produced foods were found
to be the most important predictors of PCB concentrations in residents living in
the vicinity of a former PCB manufacturing facility.
PMID- 25115607
TI - Erythropoietin ameliorates the motor and cognitive function impairments in a rat
model of hepatic cirrhosis.
AB - Hepatic encephalopathy (HE) is a serious consequence of hepatic cirrhosis (HC).
Previous studies have demonstrated cognitive impairments in both clinical and
animal experiments of HC. Some potential therapeutic agents have been used to
alleviate the cognitive symptoms in the animal models of HC. In the current
study, the possible effect of erythropoietin (ERY) as a potent neuroprotective
agent on motor and cognitive impairments induced by HC has been studied. Male
Wistar rats (180-200 g) underwent bile duct ligation (BDL) or sham surgery.
Administration of ERY (5,000 IU/kg, i.p., daily for three days) was initiated 2
weeks after surgery and lasted for the next 28 days. Open field, rotarod, Morris
water maze and passive avoidance learning was used to evaluate the motor and
cognitive function of the animals. ANOVA and repeated measures ANOVA were used to
analyze the data. p < 0.05 was considered statistically significant. BDL rats had
an increased level of hepatic enzymes and bilirubin. Impairment of balance
function by BDL was reversed by ERY. Spatial and passive avoidance learning
impairments observed in BDL rats were also reversed by chronic administration of
ERY. ERY can be offered as a potential neuroprotective agent in the treatment of
patients with HC that manifest mental dysfunctions. Though further studies are
needed to clarify the exact mechanisms, the neuroprotective properties of ERY
against BDL impairments were demonstrated in the current study.
PMID- 25115609
TI - General Practitioner Supervisor assessment and teaching of Registrars consulting
with Aboriginal patients - is cultural competence adequately considered?
AB - BACKGROUND: General Practitioner (GP) Supervisors have a key yet poorly defined
role in promoting the cultural competence of GP Registrars who provide healthcare
to Aboriginal and Torres Strait Islander people during their training placements.
Given the markedly poorer health of Indigenous Australians, it is important that
GP training and supervision of Registrars includes assessment and teaching which
address the well documented barriers to accessing health care. METHODS: A
simulated consultation between a GP Registrar and an Aboriginal patient, which
illustrated inadequacies in communication and cultural awareness, was viewed by
GP Supervisors and Medical Educators during two workshops in 2012. Participants
documented teaching points arising from the consultation which they would
prioritise in supervision provided to the Registrar. Content analysis was
performed to determine the type and detail of the planned feedback. Field notes
from workshop discussions and participant evaluations were used to gain insight
into participant confidence in cross cultural supervision. RESULTS: Sixty four of
75 GPs who attended the workshops participated in the research. Although all
documented plans for detailed teaching on the Registrar's generic communication
and consultation skills, only 72% referred to culture or to the patient's
Aboriginality. Few GPs (8%) documented a plan to advise on national health
initiatives supporting access for Aboriginal and Torres Strait Islander people. A
lack of Supervisor confidence in providing guidance on cross cultural consulting
with Aboriginal patients was identified. CONCLUSIONS: The role of GP Supervisors
in promoting the cultural competence of GP Registrars consulting with Aboriginal
and Torres Strait Islander patients could be strengthened. A sole focus on
generic communication and consultation skills may lead to inadequate
consideration of the health disparities faced by Indigenous peoples and of the
need to ensure Registrars utilise health supports designed to decrease the
disadvantage faced by vulnerable populations.
PMID- 25115610
TI - Mutations in microRNA binding sites of CEP genes involved in cancer.
AB - The CEP genes play a pivotal role in the replication of the cell. CEP family
proteins form the major constituents of the centrosome and play a prominent role
in centriole biogenesis and in cell replication. Alteration in CEP genes will
result in disruption of cell cycle that may in turn cause cancer. In our study,
we found that 16 of the CEP genes are a potential target to miRNA that binds to
complementary sequences in 3'untranslated regions (UTR) of mRNA and stop them
from translation. Single nucleotide polymorphisms (SNPs) occurring naturally in
such miRNA binding site can alter the miRNA: mRNA interaction and can
significantly alter gene expression. We developed a systematic computational
pipeline that integrates data from well-established databases, followed stringent
selection criteria and identified a panel of 44 high-confidence SNPs that may
impair miRNA target sites in the 3'UTR of 16 genes. Further we performed
expression analysis to shed light on the potential tissues that might be affected
by mutation, enrichment analysis to find the metabolic functions of the gene, and
network analysis to highlight the important interactions of CEP genes with other
genes to provide insight that complex network will be disturbed upon mutation. In
this study, we explored and prioritised the SNPs in CEP gene which could act as a
potential target in centrosome-associated human disease. Our analysis would
provide a thoughtful insight to wet lab researches to understand the expression
pattern of CEP genes and binding phenomenon of mRNA and miRNA upon mutation,
which is responsible for inhibition of translation process at genomic levels.
PMID- 25115611
TI - Is rs8099917 polymorphism of IL-28B gene a good predictor of response to therapy
of HCV than rs12979860? An Egyptian study.
AB - Hepatitis C virus (HCV) infection is the major etiology of chronic liver disease.
Polymorphisms in the IL-28B gene region are important in predicting outcome
following therapy for chronic hepatitis C virus infection. The aim of this study
was to detect the relationship between IL-28B polymorphism and responses to
therapy in patients infected with genotype 4. This study included one hundred
chronic hepatitis C patients infected with genotype 4, received PEG-IFNalpha2b
plus ribavirin for 24 weeks, as well as, 20 healthy subjects serving as control.
Clinical and laboratory parameters, including genetic variation near the IL-28B
gene (rs8099917 and rs12979860), were assessed. The results of this study showed
significant difference between responders and non-responders as regard SNPs in
the interleukin 28B gene at rs8099917 and rs12979860. In rs8099917, TT genotypes
had more frequency in responders than GG genotypes. On the other hand, CC
genotype in rs12979860 had more frequency in responders than TT genotype. By
multiple regression analysis, rs8099917 (TT), total bilirubin, and prothrombin
time were independent factors affecting the response to treatment. This results
demonstrate that in HCV genotype 4-infected patients, rs12979860 (CC) and
rs8099917 (TT) genotypes may identify patients who are likely to respond to
treatment. IL-28B SNPs are good predictors of response to combination therapy of
HCV.
PMID- 25115612
TI - Expression of MIG/CXCL9 in cystic fibrosis and modulation of its activities by
elastase of Pseudomonas aeruginosa.
AB - In cystic fibrosis (CF), colonization of the airways with Pseudomonas aeruginosa
is associated with disease deterioration. The mechanism behind the disease
progression is not fully understood. The present work shows that the
antibacterial chemokine MIG/CXCL9 is present in the airways and in sputum of CF
patients. MIG/CXCL9 showed high bactericidal activity against. P. aeruginosa,
including some strains from the airways of CF patients. Full-length MIG/CXCL9 was
detected in sputum from healthy controls and CF patients colonized with P.
aeruginosa. However, degraded MIG/CXCL9 was only found in CF sputum. In vitro,
elastase of P. aeruginosa cleaved off a fragment of similar size and two
additional fragments from MIG/CXCL9. The fragments showed less bactericidal
activity against P. aeruginosa compared with the full-length protein. The
fragments did not activate the MIG/CXCL9 receptor CXCR3 (expressed e.g. by NK
cells, mast cells, and activated T cells) but instead displayed noncompetitive
inhibition. In vitro, a decrease in CXCR3-bearing cells was found within and in
the proximity of the bronchial epithelium of CF lung tissue compared with
controls. Taken together, both bactericidal and cell-recruiting activities of
MIG/CXCL9 are corrupted by P. aeruginosa through release of elastase, and this
may contribute to impaired airway host defense in CF.
PMID- 25115613
TI - Multi-scale simulations predict responses to non-invasive nerve root stimulation.
AB - OBJECTIVE: Established biophysical neurone models have achieved limited success
in reproducing electrophysiological responses to non-invasive stimulation of the
human nervous system. This is related to our insufficient knowledge of the
induced electric currents inside the human body. Despite the numerous research
and clinical applications of non-invasive stimulation, it is still unclear which
internal sites are actually affected by it. APPROACH: We performed multi-scale
computer simulations that, by making use of advances in computing power and
numerical algorithms, combine a microscopic model of electrical excitation of
neurones with a macroscopic electromagnetic model of the realistic whole-body
anatomy. MAIN RESULTS: The simulations yield responses consistent with those
experimentally recorded following magnetic and electrical motor root stimulation
in human subjects, and reproduce the observed amplitudes and latencies for a wide
variety of stimulation parameters. SIGNIFICANCE: Our findings demonstrate that
modern computational techniques can produce detailed predictions about which and
where neurones are activated, leading to improved understanding of the physics
and basic mechanisms of non-invasive stimulation and enabling potential new
applications that make use of improved targeting of stimulation.
PMID- 25115614
TI - De novo renal cell carcinoma in a kidney allograft with focus on contrast
enhanced ultrasound.
AB - The development of de novo renal cell carcinoma (RCC) in a transplanted kidney is
a rare condition. Currently, this is the second case report of a 41-year-old man
in whom carcinoma of a renal allograft was detected by contrast-enhanced
ultrasound (CEUS). An abdominal CT scan was not conclusive enough to
differentiate between septal enhancement of a cyst and a low vascularized tumor.
CEUS confirmed a solid, homogeneously enhancing but hypoechoic and hypovascular
lesion compared to the surrounding kidney parenchyma without septal enhancement.
Therefore, the patient underwent nephron-sparing surgery (NSS), affirming
papillary RCC type 2. Graft function remained unchanged postoperatively; 12
months after NSS, no local recurrence or distant metastasis was described. CEUS
seems to be a minimally invasive and efficient imaging option if other diagnostic
tools cannot clearly exclude RCC, with the advantage of wide-ranging use,
especially in cases of impaired renal function.
PMID- 25115615
TI - Prevalence of non-polypoid colorectal neoplasms in southern Brazil.
AB - BACKGROUND AND AIM: Several studies suggest that non-polypoid lesions (NPL) show
higher aggressiveness than polypoid lesions, particularly depressed lesions. The
present study aimed to assess the prevalence of NPL and the presence of advanced
histology in a Brazilian population. METHODS: Two thousand and sixty-seven
superficial neoplastic lesions diagnosed in 1135 patients were analyzed. Lesions
were classified as polypoid and non-polypoid (flat and depressed) types, and
evaluated for site, size, and histology (adenoma with grade of dysplasia, or
early cancer). RESULTS: Prevalence of NPL was 46.5%. NPL predominated in the
right colon (62.9%), whereas polypoid lesions were detected mainly in the left
colon (53.2%) (P < 0.001). NPL had a 34% higher probability of occurring in the
right colon than polypoid lesions (P < 0.001). NPL were smaller than polypoid
lesions (P = 0.03). There were 208 lesions >10 mm, of which 40 (19.2%) had
advanced histology: 13% (18/138) of polypoid lesions; 27.3% (18/66) of flat
lesions; and 100% (4/4) of depressed lesions (P < 0.001). Among 1859 neoplasms
<=10 mm, only 18 (1%) had advanced histology, and 15 of them were depressed
lesions (P < 0.001). Advanced histology was more commonly detected in NPL than in
polypoid lesions (P = 0.007), with significant difference in size (P < 0.001).
NPL showed more advanced histology than polypoid lesions (OR 2.06; P = 0.01),
especially depressed lesions (OR 36.35; P < 0.001). Among all neoplasms, the
prevalence of depressed lesions was 2.2%. CONCLUSION: NPL showed high prevalence
and higher aggressiveness than polypoid lesions, especially the depressed type.
PMID- 25115617
TI - Patients' perspectives on hemodialysis vascular access: a systematic review of
qualitative studies.
AB - BACKGROUND: Delayed creation of vascular access may be due in part to patient
refusal and is associated with adverse outcomes. Concerns about vascular access
are prevailing treatment-related stressors for patients on hemodialysis therapy.
This study aims to describe patients' perspectives on vascular access initiation
and maintenance in hemodialysis. STUDY DESIGN: Systematic review and thematic
synthesis of qualitative studies. SETTING & POPULATION: Patients with chronic
kidney disease who express opinions about vascular access for hemodialysis.
SEARCH STRATEGY & SOURCES: MEDLINE, EMBASE, PsycINFO, CINAHL, reference lists,
and PhD dissertations were searched to October 2013. ANALYTICAL APPROACH:
Thematic synthesis was used to analyze the findings. RESULTS: From 46 studies
involving 1,034 patients, we identified 6 themes: heightened vulnerability
(bodily intrusion, fear of cannulation, threat of complications and failure,
unpreparedness, dependence on a lifeline, and wary of unfamiliar providers),
disfigurement (preserving normal appearance, visual reminder of disease, and
avoiding stigma), mechanization of the body (bonded to a machine, internal
abnormality, and constant maintenance), impinging on way of life (physical
incapacitation, instigating family tension, wasting time, and added expense),
self-preservation and ownership (task-focused control, advocating for protection,
and acceptance), and confronting decisions and consequences (imminence of
dialysis therapy and existential thoughts). LIMITATIONS: Non-English articles
were excluded. CONCLUSIONS: Vascular access is more than a surgical intervention.
Initiation of vascular access signifies kidney failure and imminent dialysis,
which is emotionally confronting. Patients strive to preserve their vascular
access for survival, but at the same time describe it as an agonizing reminder of
their body's failings and "abnormality" of being amalgamated with a machine
disrupting their identity and lifestyle. Timely education and counseling about
vascular access and building patients' trust in health care providers may improve
the quality of dialysis and lead to better outcomes for patients with chronic
kidney disease requiring hemodialysis.
PMID- 25115616
TI - A randomized, placebo-controlled trial of pentoxifylline on erythropoiesis
stimulating agent hyporesponsiveness in anemic patients with CKD: the Handling
Erythropoietin Resistance With Oxpentifylline (HERO) trial.
AB - BACKGROUND: Erythropoiesis-stimulating agent (ESA)-hyporesponsive anemia is
common in chronic kidney disease (CKD). Pentoxifylline shows promise as a
treatment for ESA-hyporesponsive anemia, but has not been rigorously evaluated.
STUDY DESIGN: Multicenter, double-blind, randomized, controlled trial. SETTING &
PARTICIPANTS: 53 adult patients with CKD stage 4 or 5 (including dialysis) and
ESA-hyporesponsive anemia (hemoglobin<=120g/L and ESA resistance index
[calculated as weight-adjusted weekly ESA dose in IU/kg/wk divided by hemoglobin
concentration in g/L]>=1.0IU/kg/wk/g/L for erythropoietin-treated patients and
>=0.005MUg/kg/wk/g/L for darbepoetin-treated patients). INTERVENTIONS:
Pentoxifylline (400mg/d; n=26) or matching placebo (control; n=27) for 4 months.
OUTCOMES: PRIMARY OUTCOME: ESA resistance index at 4 months; secondary outcomes:
hemoglobin concentration, ESA dose, blood transfusion requirement, serum ferritin
level and transferrin saturation, C-reactive protein level, adverse events,
quality of life, and health economics. RESULTS: There was no statistically
significant difference in ESA resistance index between the pentoxifylline and
control groups (adjusted mean difference, -0.39 [95%CI, -0.89 to 0.10]
IU/kg/wk/g/L; P=0.1). Pentoxifylline significantly increased hemoglobin
concentration relative to the control group (adjusted mean difference, 7.6
[95%CI, 1.7-13.5] g/L; P=0.01). There was no difference in ESA dose between
groups (-20.8 [95%CI, -67.2 to 25.7] IU/kg/wk; P=0.4). No differences in blood
transfusion requirements, adverse events, or quality of life were observed
between groups. Pentoxifylline cost A$88.05 (US $82.94) per person over the trial
and produced mean savings in ESA cost of A$1,332 (US $1,255). The overall
economic impact over the trial period was a saving of A$1,244 (US $1,172) per
person for the pentoxifylline group compared with controls. LIMITATIONS: Sample
size smaller than planned due to slow recruitment. CONCLUSIONS: Pentoxifylline
did not significantly modify ESA hyporesponsiveness, but increased hemoglobin
concentration. Further studies are warranted to determine whether pentoxifylline
therapy represents a safe strategy for increasing hemoglobin levels in patients
with CKD with ESA-hyporesponsive anemia.
PMID- 25115619
TI - Predictors of anxiety in centenarians: health, economic factors, and loneliness.
AB - BACKGROUND: Centenarians' psychological well-being is presently of great interest
in psychogeriatric research but little is known about factors that specifically
account for the presence of clinically relevant anxiety symptoms in this age
group. This study examined the presence of anxiety and its predictors in a sample
of centenarians and aims to contribute to a better understanding of anxiety
determinants in extreme old age. METHODS: We examined how socio-demographic,
health, functional, and social factors contribute to the presence of clinically
significant anxiety symptoms in centenarians recruited from two Portuguese
centenarian studies. The Geriatric Anxiety Inventory - Short Form (GAI-SF) was
used to assess anxiety symptoms. RESULTS: A total of 97 centenarians (mean age
101.1 years; SD = 1.5 years; range = 100-108) with no/minor cognitive impairment
were included. Clinically significant anxiety symptoms (GAI-SF >=3) were present
in 45.4% (n = 44) of the sample. Main predictive factors included worse health
perception, higher number of medical conditions, financial concerns related to
medical expenses (income inadequacy) and loneliness. CONCLUSIONS: Results suggest
that along with health status (subjective and objective), income inadequacy
related to medical expenses and feeling lonely may predispose centenarians to
clinically significant anxiety and be important to their overall well-being.
Further research is needed on the repercussions of clinical anxiety in
centenarians' quality of life and on co-morbid conditions (e.g. depression) at
such advanced ages.
PMID- 25115618
TI - Construct and concurrent validity of a patient-reported adverse drug event
questionnaire: a cross-sectional study.
AB - BACKGROUND: Direct patient-reported information about adverse drug events (ADEs)
is important since it adds to healthcare professional-reported information about
the safety of drugs. Previously, we developed an instrument to assess patient
reported ADEs in research settings. The aim of this study is to assess the
construct and concurrent validity of the questionnaire. METHODS: Patients on at
least an oral glucose-lowering drug completed the ADE questionnaire, the World
Health Organization Quality of Life-BREF, and the Treatment Satisfaction
Questionnaire for Medication (TSQM). The ADE questionnaire assesses ADEs for any
drug that the patient uses. Construct validity was assessed by testing whether
patients reporting an ADE had a lower general quality of life and physical health
than those not reporting an ADE, using Mann-Whitney U-tests and t-tests
(significance level <0.05). For concurrent validity, we tested whether ADEs that
patients associate with particular drugs in the ADE questionnaire are documented
in the Summary of Product Characteristics (SPC) of those drugs, and whether
patients who report an ADE with the use of metformin on the TSQM, mention
metformin as a drug associated with an ADE on the ADE questionnaire. Agreement of
70% with the SPC was considered satisfactory. Sensitivity and positive predictive
value (PPV) were calculated for the comparison with the TSQM, where 70% was used
as the cut-off level for sufficient concurrent validity. RESULTS: We included 135
patients (mean age 64 years, 35% women). Patients who reported an ADE (N = 37)
had a lower general quality of life and physical health than those not reporting
an ADE (P < 0.05). For 78 of the 146 reported ADEs (53%), patients mentioned at
least 1 particular drug associated with the ADE. After clustering related ADEs,
this resulted in 56 patient-reported ADE-drug associations. Of these, 41 (73%)
were in agreement with information in the SPC. Finally, the questionnaire had a
sensitivity of 38% and PPV of 79% for assessing ADEs associated with metformin.
CONCLUSIONS: The construct validity of the patient-reported ADE questionnaire was
sufficient for reporting any versus no ADE, but the concurrent validity was only
partly demonstrated. Therefore, the questionnaire needs to be adapted before it
can be used.
PMID- 25115620
TI - Stimulus-specific adaptation in the inferior colliculus of the mouse: anesthesia
and spontaneous activity effects.
AB - Rapid behavioral responses to unexpected events in the acoustic environment are
critical for survival. Stimulus-specific adaptation (SSA) is the process whereby
some auditory neurons respond better to rare stimuli than to repetitive stimuli.
Most experiments on SSA have been performed under anesthesia, and it is unknown
if SSA sensitivity is altered by the anesthetic agent. Only a direct comparison
can answer this question. Here, we recorded extracellular single units in the
inferior colliculus of awake and anesthetized mice under an oddball paradigm that
elicits SSA. Our results demonstrate that SSA is similar, but not identical, in
the awake and anesthetized preparations. The differences are mostly due to the
higher spontaneous activity observed in the awake animals, which also revealed a
high incidence of inhibitory receptive fields. We conclude that SSA is not an
artifact of anesthesia and that spontaneous activity modulates neuronal SSA
differentially, depending on the state of arousal. Our results suggest that SSA
may be especially important when nervous system activity is suppressed during
sleep-like states. This may be a useful survival mechanism that allows the
organism to respond to danger when sleeping.
PMID- 25115621
TI - Central arterial pulse waveform acquisition with a portable pen-like optical
fiber sensor.
AB - OBJECTIVE: Pulse waveform features related to cardiovascular pathologies and
arterial stiffness have been extensively studied, and optical fiber sensors have
been studied with an aim to simplify the pulse waveform acquisition in the
carotid artery. In this paper, a novel optical fiber sensor to record pulse
waveform in the carotid artery has been proposed. METHODS: The pulse waveform
optical fiber sensor design, based on fiber Bragg gratings, is presented. The
probe was characterized, and its response to controlled waveforms was studied.
Finally, tests were performed on human subjects. RESULTS: The developed sensor
has a displacement sensitivity of 21.2 pm/MUm, with ability to detect the carotid
pulse wave in the neck surface, with a resolution of 1.3 mmHg. CONCLUSION: This
study revealed a new technological approach for acquisition of the central pulse
waveform.
PMID- 25115622
TI - In response: ambulatory blood pressure measurement in pharmacies.
PMID- 25115623
TI - Planar edge Schottky barrier-tunneling transistors using epitaxial graphene/SiC
junctions.
AB - A purely planar graphene/SiC field effect transistor is presented here. The
horizontal current flow over one-dimensional tunneling barrier between planar
graphene contact and coplanar two-dimensional SiC channel exhibits superior
on/off ratio compared to conventional transistors employing vertical electron
transport. Multilayer epitaxial graphene (MEG) grown on SiC(0001) was adopted as
the transistor source and drain. The channel is formed by the accumulation layer
at the interface of semi-insulating SiC and a surface silicate that forms after
high vacuum high temperature annealing. Electronic bands between the graphene
edge and SiC accumulation layer form a thin Schottky barrier, which is dominated
by tunneling at low temperatures. A thermionic emission prevails over tunneling
at high temperatures. We show that neglecting tunneling effectively causes the
temperature dependence of the Schottky barrier height. The channel can support
current densities up to 35 A/m.
PMID- 25115624
TI - Effect of extraction technique on the content and antioxidant activity of crude
extract of Anacyclus clavatus flowers and their essential oil composition.
AB - Anacyclus clavatus is a plant used as food and remedy. The objective of this work
was to study the effect of extraction technique on the antioxidant property,
total phenol and flavonoid contents of crude extracts from A. clavatus flowers
and their essential oil composition. 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay,
ferric-reducing power, beta-carotene and total antioxidant capacity assays have
demonstrated the significant antioxidant ability of different crude extracts
obtained by using the following extraction methods: Soxhlet, microwave heating,
heat reflux (HRE) and maceration. The activity of the extract obtained by HRE was
the highest (112.06 +/- 2.89 MUg/mL) evaluated by the DPPH assay. Extraction of
essential oil was performed by microwave-assisted hydro-distillation (MAHD) and
by hydro-distillation (HD). A significant difference was observed in both
essential oils, despite the common main family and major constituents, such as
artemisia ketone (10.0 +/- 0.8% for MAHD vs. 6.5 +/- 0.5 for HD) and pinocarvone
(4.1 +/- 0.4% for MAHD vs. 1.1 +/- 0.1% for HD).
PMID- 25115625
TI - Synthesis of tetrahydropyridine derivatives through a modular assembly reaction
using 3,4-dihydropyran as dual substrate and template.
AB - A concise method to synthesize 1,2,3,4-tetrahydropyridines is described that
involves the use of 2-alkoxy-3,4-dihydropyran as a modular precursor to react
with aniline and a nucleophile. In this method, the heteroatom of the
dihydropyran ring was replaced by nitrogen of aniline while the nucleophile
attached to its adjacent position. Various druglike polyheterocycles were
prepared with this method by using NH2-containing 1,5- or 1,4-bisnucleophiles.
PMID- 25115626
TI - Scaffold hopping of sampangine: discovery of potent antifungal lead compound
against Aspergillus fumigatus and Cryptococcus neoformans.
AB - Discovery of novel antifungal agents against Aspergillus fumigatus and
Cryptococcus neoformans remains a significant challenge in current antifungal
therapy. Herein the antifungal natural product sampangine was used as the lead
compound for novel antifungal drug discovery. A series of D-ring scaffold hopping
derivatives were designed and synthesized to improve antifungal activity and
water solubility. Among them, the thiophene derivative S2 showed broad-spectrum
antifungal activity, particularly for Aspergillus fumigatus and Cryptococcus
neoformans. Moreover, compound S2 also revealed better water solubility than
sampangine, which represents a promising antifungal lead compound for further
structural optimization.
PMID- 25115628
TI - In vitro dynamic degradation behavior of new magnesium alloy for orthopedic
applications.
AB - We report on methodologies for use in the design of a biodegradable Mg alloy
appropriate for load-bearing but temporary orthopedic implant applications.
Comparative studies of Mg-5Ca and Mg-5Ca-1Zn were conducted to explore the
effects of a combination of minor alloying and hot extrusion, on the alloy's
mechanical properties and corrosion resistance. The extruded Mg-5Ca-1Zn exhibited
high ultimate compressive strength of 385 MPa and suffered no significant
structural degradation even after immersion in simulated body fluid for 30 days.
Mg-5Ca-1Zn alloy showed the mechanical strength and controlled corrosion rate to
be considered as an ideal candidate for biodegradable orthopedic implant
material.
PMID- 25115627
TI - Moderate hypoxia influences potassium outward currents in adipose-derived stem
cells.
AB - Moderate hypoxic preconditioning of adipose-derived stem cells (ASCs) enhances
properties such as proliferation and secretion of growth factors, representing a
valuable strategy to increase the efficiency of cell-based therapies. In a wide
variety of cells potassium (K+) channels are key elements involved in the
cellular responses to hypoxia, suggesting that ASCs cultured under low oxygen
conditions may display altered electrophysiological properties. Here, the effects
of moderate hypoxic culture on proliferation, whole-cell currents, and ion
channel expression were investigated using human ASCs cultured at 5% and 20%
oxygen. Although cell proliferation was greatly enhanced, the dose-dependent
growth inhibition by the K+ channel blocker tetraethylammonium (TEA) was not
significantly affected by hypoxia. Under both normoxic and hypoxic conditions,
ASCs displayed outward K+ currents composed by Ca2+-activated, delayed rectifier,
and transient components. Hypoxic culture reduced the slope of the current
voltage curves and caused a negative shift in the voltage activation threshold of
the whole-cell currents. However, the TEA-mediated shift of voltage activation
threshold was not affected by hypoxia. Semiquantitative real-time RT-PCR revealed
that expression of genes encoding for various ion channels subunits related to
oxygen sensing and proliferation remained unchanged after hypoxic culture. In
conclusion, outward currents are influenced by moderate hypoxia in ASCs through a
mechanism that is not likely the result of modulation of TEA-sensitive K+
channels.
PMID- 25115629
TI - Validation and reference ranges of hair cortisol measurement in healthy children.
AB - BACKGROUND: Cortisol is produced in a circadian rhythm controlled by the
hypothalamus-pituitary-adrenal axis, making it cumbersome to measure long-term
cortisol exposure. Hair has proven to be a reliable matrix for long-term cortisol
measurement in adults and can be used as diagnostic tool for (cyclic) Cushing's
syndrome. The diagnostic applicability in children has not been studied, nor have
the effects of development and hair care been evaluated in children. We aimed to
establish reference ranges of hair cortisol concentrations (HCC) in healthy
children and to evaluate the effects of age, gender, puberty and characteristics
of hair care. METHODS: In 128 healthy children aged 4-14 years, HCC were measured
in a small 3-cm hair lock from the back of the head. RESULTS: HCC increased with
age (p = 0.04) up to age 10 years, with a mean of 5.0, 5.8, 6.8 and 8.5 pg/mg at
age 4-5, 6-7, 8-9 and 10-14 years, respectively. Children aged 4-7 years had
significantly lower HCC compared to healthy adults (p = 0.007). We did not find
any influence of gender, puberty or hair care characteristics on hair cortisol.
CONCLUSION: HCC can be reliably measured in childhood, and reference ranges
increase with age. HCC in children are not dependent on hair care or hair
characteristics.
PMID- 25115630
TI - Diaminoglyoxime as a versatile reagent in the synthesis of bis(1,2,4
oxadiazoles), 1,2,4-oxadiazolyl-quinazolines and 1,2,4-oxadiazolyl
benzothiazinones.
AB - The synthesis of bis(1,2,4-oxadiazoles), 1,2,4-oxadiazolyl-quinazolines, and
1,2,4-oxadiazolyl-benzothiazinones has been investigated by the reaction of
diaminoglyoxime with various ketones and methyl 2-aminobenzoate, 2-amino-5
chlorophenyl)(phenyl)methanone, and 2-mercapto benzoic acid in acetic acid either
a catalyst or solvent at 100 degrees C.
PMID- 25115631
TI - Expression of Neural Wiskott-Aldrich Syndrome Protein in Clear Cell Renal Cell
Carcinoma and Its Correlation with Clinicopathological Features.
AB - INTRODUCTION: Neural Wiskott-Aldrich syndrome protein (N-WASP) expression is
associated with tumor cell invasion and migration. However, its expression status
in clear cell renal cell carcinoma (CCRCC) remains unclear. We examined the level
of N-WASP in CCRCC and its association with clinicopathological features
characteristic. MATERIALS AND METHODS: 73 CCRCC patients who underwent radical
nephrectomy or partial nephrectomy were enrolled. Immunohistochemical staining
for N-WASP was performed on tissue microarrays constructed from tumor and para
tumor tissue obtained from these patients. The difference in N-WASP expression
between tumor tissue and adjacent normal renal tissue was examined. Correlations
between N-WASP expression in the tumor and clinicopathological parameters were
analyzed and the relationship between N-WASP expression and overall survival also
assessed. Uni- and multivariate survival analyses were performed. RESULTS: N-WASP
expression was significantly reduced in tumor tissues and was significantly
related to the histological grade of CCRCC. A higher level of N-WASP expression
in the tumor was associated with relatively poor survival in CCRCC patients. The
level of N-WASP expression, age at time of surgery, and histological grade were
all responsible for clinical outcome in CCRCC patients. N-WASP was an independent
predictor for overall survival. CONCLUSIONS: N-WASP was downregulated in CCRCC
and could serve as a prognostic biomarker for predicting clinical outcome of
CCRCC.
PMID- 25115632
TI - Efficiency of pretreatment risk stratification systems for prostate cancer in a
Japanese population treated with radical prostatectomy.
AB - OBJECTIVE: To determine whether the currently available pretreatment risk
classification systems are applicable in Japanese prostate cancer patients.
METHODS: Using data obtained from 1264 consecutive patients with prostate cancer
treated with radical prostatectomy at four hospitals in Japan, biochemical
recurrence-free survival rates were estimated and compared between the D'Amico,
the National Institute for Health and Clinical Excellence, the Cancer of the
Prostate Strategic Urological Research Endeavor, the National Comprehensive
Cancer Network, and the European Society of Medical Oncology risk groups by using
the Kaplan-Meier method and log-rank test. RESULTS: The 5-year biochemical
recurrence-free survival rates in the D'Amico low-, intermediate-, and high-risk
groups were 88.3%, 84.7% and 66.9%, respectively (low and intermediate risk vs
high risk, P < 0.001). The 5-year biochemical recurrence-free survival rates in
the National Institute for Health and Clinical Excellence, National Comprehensive
Cancer Network, and European Society of Medical Oncology low-, intermediate- and
high-risk groups were 88.3%, 84.3%, and 60.3%, respectively (low and intermediate
risk vs high risk, P < 0.001). The 5-year biochemical recurrence-free survival
rates in the Cancer of the Prostate Strategic Urological Research Endeavor low-,
intermediate-, and high-risk groups were 90%, 83.5% and 60.3%, respectively (low
and intermediate risk vs high risk, P < 0.001). Low- and intermediate-risk groups
according to any of the risk stratification systems did not show significant
differences in biochemical recurrence-free survival. CONCLUSION: Current risk
stratification systems do not discriminate between low- and intermediate-risk
groups in the Japanese population. A novel, pretreatment risk stratification
system including other prognostic factors is necessary for an adequate prostate
cancer risk assessment in the Japanese population.
PMID- 25115633
TI - High plasma levels of HLA-G are associated with low birth weight and with an
increased risk of malaria in infancy.
AB - BACKGROUND: The immunosuppressive properties of HLA-G protein can create a
tolerogenic environment that may allow Plasmodium falciparum to avoid host immune
responses. There are known associations between high levels of circulating
soluble HLA-G (sHLA-G) and either parasite or viral infections and it has been
suggested that the induction of sHLA-G expression could be a mechanism via which
infectious agents subvert host immune defence. The study presented here is the
first to investigate the possible association between sHLA-G and malaria or
malaria related risk factors in Benin. METHODS: A parasitological and clinical
follow-up of 165 mothers and their newborns from delivery through to one year of
age was conducted in the Tori Bossito area of southern Benin. Plasma levels of
sHLA-G were determined by ELISA in maternal peripheral and cord blood and again
in infants' peripheral blood at 3, 6, 9 and 12 months of age. The associations
between the levels of sHLA-G and malaria risk factors were investigated through
multivariate mixed models. RESULTS: Strong correlations were observed between the
maternal and cord plasma concentrations of sHLA-G. In multivariate analyses, high
cord plasma levels of sHLA-G were independently associated with (i) low birth
weight and (ii) an increased risk of P. falciparum infection in infancy.
CONCLUSION: These results show for the first time the possible involvement of
sHLA-G in generating immune tolerance during pregnancy-associated malaria.
Soluble HLA-G may represent a useful marker of susceptibility to malaria in
infants and be associated with the higher susceptibility to infection observed
for LBW children.
PMID- 25115634
TI - Health related quality of life of children and adolescents with congenital
adrenal hyperplasia in Brazil.
AB - BACKGROUND: Congenital Adrenal Hyperplasia (CAH) is an endocrine disorder
characterized by enzymatic deficiency in adrenal steroidogenesis, leading to
adrenal insufficiency and hyperandrogenism. Patients need continuous hormone
replacement therapy, but adequate control has proven challenging, exposing
patients to undesirable consequences of both disease and treatment. OBJECTIVE: To
evaluate the health related quality of life (HRQoL) of children and adolescents
with CAH due to 21-hydroxylase deficiency. METHODS: In an analytical study,
generic questionnaires, validated and translated versions, Pediatric Quality of
Life Inventory 4.0 (for self-assessment of patients) and Child Health
Questionnaire - PF50 (for parents) were applied and mean scores were analyzed
with Student's t-test. RESULTS: We included 25 patients (19 female) with
classical CAH (14 salt wasting/11 simple virilizing), mean age +/- standard
deviation (SD) of 11.4 +/- 3.6 years (5-17.9), and their parents. Self-assessment
of HRQOL showed decrease in mean scores: overall (67.8 +/- 15.5 vs. 88.9 +/- 7.4,
p value = 0.015) and in the physical (75.2 +/- 15.0 vs. 95.9 +/- 5.8, p value =
0.014) and psychosocial (63.9 +/- 17.8 vs. 85.0 +/- 9.6, p value = 0.023)
dimensions of patients, compared to healthy controls (previously published
national data on children and adolescents). The assessment of the parent's view
was concordant, also showing losses in the physical (43.7 +/- 8.0 vs. 55.1 +/-
3.6, p value = 0.013) and psychosocial (41.9 +/- 9.7 vs. 53.0 +/- 7.0, p value =
0.025) dimensions. The comparison of HRQOL between subgroups 1) males versus
females and 2) salt-wasting versus simple virilizing showed no significant
differences. CONCLUSION: There seems to be a loss of HRQOL in children and
adolescents with classical CAH. The self-assessment was concordant in key areas
with the assessment made by their parents. No differences were observed between
genders or clinical presentation of the disease.
PMID- 25115636
TI - The effect of anagliptin treatment on glucose metabolism and lipid metabolism,
and oxidative stress in fasting and postprandial states using a test meal in
Japanese men with type 2 diabetes.
PMID- 25115635
TI - Effect of GLP-1 receptor agonists on waist circumference among type 2 diabetes
patients: a systematic review and network meta-analysis.
AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used in
patients with type 2 diabetes. However, the effect on abdominal obesity has not
yet been confirmed. The study aimed to systematically evaluate the effect of GLP
1RAs on waist circumference in patients with type 2 diabetes. MEDLINE, EMBASE,
the Cochrane library and www.clinicaltrialgov were searched through October 31,
2013. Randomized controlled trials with available data were selected if they
compared GLP-1 RAs with placebo and traditional anti-diabetic drugs with a
duration>=8 weeks. Weighted mean difference was estimated using random-effect
model. Network meta-analysis was performed to supplement direct comparisons.
Seventeen trials with 12 treatments were included. Overall, significant
reductions on waist circumference following treatment of liraglutide--1.8 mg once
daily (-5.24 cm, 95% CI -7.68, -2.93), liraglutide--1.2 mg once daily (-4.73 cm,
95% CI -6.68, -2.65) and exenatide--10 MUg twice daily (-1.34 cm, 95 % CI -2.00,
0.75) were detected versus placebo. The reduction effect was more evident when
compared with insulin and thiazolidinediones (range -1.71 to -8.03 cm). Compared
with exenatide, liraglutide--0.6 mg once daily, taspoglutide, liraglutide--1.2 mg
once daily and liraglutide--1.8 mg once daily significantly decreased waist
circumference from -3.32 to -6.01 cm. Besides, liraglutide--1.8 mg once daily
significantly decreased waist circumference by -1.73 cm (95 % CI -3.04, -0.55)
versus sitagliptin, whereas no significant difference following liraglutide--1.2
mg-once-daily treatment was detected compared with liraglutide--1.8 mg once daily
and sitagliptin. Reduction was observed with statistical significance for
exenatide--10 MUg twice daily compared with exenatide--5 MUg twice daily (-1.21
cm, 95% CI -2.43, -0.06). Ranking probability analysis indicated liraglutide--1.8
mg once daily and liraglutide--1.2 mg once daily decreased waist circumference
most among all 12 treatments with probability of 98.36% and 91.82%, respectively.
Some GLP-1RAs, especially liraglutide--1.8 mg once daily and liraglutide--1.2 mg
once daily, were associated with a significant reduction in waist circumference.
PMID- 25115637
TI - Comparison of salivary and calculated free cortisol levels during low and
standard dose of ACTH stimulation tests in healthy volunteers.
AB - Salivary cortisol (SC) has been increasingly used as a surrogate biomarker of
free cortisol (FC) for the assessment of hypothalamo-pituitary-adrenal (HPA)
axis, but there are not enough data regarding its use during ACTH stimulation
tests. Therefore, we aimed to determine the responses of SC, calculated free
cortisol (cFC) and free cortisol index (FCI) to ACTH stimulation tests in healthy
adults. Forty-four healthy volunteers (24 men and 20 women) were included in the
study. Low-dose (1 ug) and standard-dose (250 ug) ACTH stimulation tests were
performed on two consecutive days. Basal and stimulated total cortisol (TC) and
cortisol-binding globulin (CBG) levels and SC levels were measured during both
doses of ACTH stimulation tests. cFC (by Coolens' equation) and FCI levels were
calculated from simultaneously measured TC and CBG levels. The minimum SC, cFC,
FCI levels after low-dose ACTH stimulation test were 0.21, 0.33, 16.06 ug/dL, and
after standard-dose ACTH were 0.85, 0.46, 26.11 ug/dL, respectively, in healthy
individuals who all had TC responses higher than 20 ug/dL. Peak CBG levels after
both doses of ACTH stimulation tests were found to be higher in women than in
men. So, by its effect, peak cFC and FCI levels were found to be lower in female
than in male group. Neither TC nor SC levels were affected by gender. cFC and FCI
levels depend on CBG levels and they are affected by gender. Cut-off levels for
SC, cFC, FCI levels after both low- and standard-dose ACTH stimulation are
presented. Studies including patients with adrenal insufficiency would be helpful
to see the diagnostic value of these suggested cut-off levels.
PMID- 25115642
TI - Detecting alcohol problems in older adults: can we do better?
PMID- 25115643
TI - Mechanistic insights into the reduction of graphene oxide addressing its
surfaces.
AB - Both sides of a graphene oxide (ai-GO) layer are decorated with functional
groups. For the first time it is demonstrated that an effective reduction of ai
GO to graphene can be performed, even if the reducing agent can access only one
side of ai-GO. A general reduction mechanism is proposed.
PMID- 25115638
TI - PI3K/Akt/mTOR signaling in medullary thyroid cancer: a promising molecular target
for cancer therapy.
AB - The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR)
pathway is a central hub for the regulation of cell proliferation, apoptosis,
cell cycle, metabolism, and angiogenesis. Several studies have recently suggested
that the PI3K/Akt/mTOR signaling pathway is implicated in the pathogenesis and
progression of neuroendocrine tumors. Medullary thyroid cancer (MTC) is a
neuroendocrine tumor developing from the C cells of the thyroid. Mutations in the
RET proto-oncogene are involved in the pathogenesis of several forms of MTC. The
deregulation of the PI3K/Akt/mTOR pathway seems to contribute to the tumorigenic
activity of RET proto-oncogene mutations. Targeting this pathway through specific
inhibitors at simple or multiple sites may represent an attractive potential
therapeutic approach for patients with advanced MTCs. The aim of this review is
to examine the role of the PI3K/Akt/mTOR pathway in the development and
progression of MTC and the new therapeutic options that target this signaling
pathway.
PMID- 25115644
TI - Copper(II) catalyzed expeditious synthesis of furoquinoxalines through a one-pot
three-component coupling strategy.
AB - Microwave assisted one-pot transformation has been developed for the synthesis of
biologically significant polysubstituted furoquinoxalines in good to excellent
yields through a copper(II) catalyzed three-component coupling of o
phenylenediamine, ethylglyoxalate, and terminal alkyne, known as A(3)-coupling,
followed by 5-endo-dig cyclization.
PMID- 25115646
TI - In vitro biological activities and fatty acid profiles of Pistacia terebinthus
fruits and Pistacia khinjuk seeds.
AB - This study reports in vitro anticholinesterase, antioxidant and antimicrobial
effects of the n-hexane, dichloromethane, ethanol and ethanol-water extracts
prepared from Pistacia terebinthus L. fruits and Pistacia khinjuk Stocks seeds as
well as their total phenolic and flavonoid contents, and fatty acid compositions.
Ethanol and ethanol-water extracts of both species exhibited higher
anticholinesterase activity than galanthamine. Among ABTS, DPPH and CUPRAC
assays, the highest antioxidant capacity of the extracts was found in the last
one. P. terebinthus ethanol extract being rich in flavonoid content showed the
best cupric reducing effect. All extracts possessed no antimicrobial activity.
The main fatty acid in P. terebinthus fruits (52.52%) and P. khinjuk seeds
(59.44%) was found to be oleic acid. Our results indicate that P. terebinthus
fruits and P. khinjuk seeds could be a good source of anticholinesterase
compounds, and could be phytochemically investigated.
PMID- 25115645
TI - Oxidized multiwalled carbon nanotubes as antigen delivery system to promote
superior CD8(+) T cell response and protection against cancer.
AB - Properties like high interfacial area with cellular membranes, unique ability to
incorporate multiple functionalization, as well as compatibility and transport in
biological fluids make carbon nanotubes (CNTs) useful for a variety of
therapeutic and drug-delivery applications. Here we used a totally synthetic
hybrid supramolecule as an anticancer vaccine formulation. This complex structure
comprises CNTs as delivery system for the Cancer Testis Antigen named NY-ESO-1,
allied to a synthetic Toll-Like Receptor agonist. The CNT constructs were rapidly
internalized into dendritic cells, both in vitro and in vivo, and served as an
intracellular antigen depot. This property favored the induction of strong CD4(+)
T as well as CD8(+) T cell-mediated immune responses against the NY-ESO-1.
Importantly, the vaccination significantly delayed the tumor development and
prolonged the mice survival, highlighting the potential application of CNTs as a
vaccine delivery system to provide superior immunogenicity and strong protection
against cancer.
PMID- 25115647
TI - The effect of actual and imaginary handgrip on postural stability during
different balance conditions.
AB - The stabilizing effect of holding an object on upright posture has been
demonstrated in a variety of settings. The mechanism of this effect is unknown
but could be attributed to either additional sensorimotor activity triggered by a
hand contact or cognitive efforts related to performance of a supra-postural
task. A potential mechanism was investigated by comparing postural stability in
young healthy individuals while gripping a custom instrumented wooden stick with
a 5N force and while imagining holding the same stick in the hand. Twenty
subjects were tested during three standing balance conditions: on a stationary
surface, on a freely moving rockerboard, and with an unexpected perturbation of
10 degrees forward rockerboard tipping. Postural stability was evaluated as
velocity of the center of mass (COM) and center of pressure (COP) compared across
all experimental conditions. COM and COP velocities were equally reduced when
subjects gripped the stick and imagined gripping while standing stationary and on
the rockerboard. When perturbed, subjects failed to show any postural stability
improvements regardless of handgrip task. Results indicate a stabilizing effect
of focusing attention on motor task performance. This cognitive strategy does not
appear to contribute any additional stabilization when subjects are perturbed.
This study adds to the current understanding of postural stabilization
strategies.
PMID- 25115648
TI - In vivo investigations on luteotropic activity of prostaglandins during early
diestrus in nonpregnant bitches.
AB - The aim of this study was to test for the postulated luteotropic effect of
prostaglandin E2 during early diestrus in the dog in an in vivo study. This study
was performed on 30 bitches which were randomly assigned to a treatment group
(TG) and a control group. Starting on the day of ovulation (Day 0), dogs of the
TG were treated for 5, 10, 20, or 30 days with 10 mg firocoxib/kg body weight per
day (Previcox, a selective PTGS2 inhibitor) and ovariohysterectomized for
collection of corpora lutea on the last day of treatment. Similarly, dogs of the
control group were ovariohysterectomized on Days 0, 5, 10, 20, and 30. Blood
samples for progesterone measurement were collected every second day;
additionally, the area of luteal cell nuclei and the expression of 3beta
hydroxysteroid-dehydrogenase at the mRNA and the protein levels were assessed.
Mean P4 concentrations were lower in TGs; however, a significant difference was
only observed on Day 10. This observation is in line with the finding that
treatment with firocoxib reduced expression of 3beta-hydroxysteroid-dehydrogenase
mRNA and protein (P < 0.05) and the area of luteal cell nuclei (P < 0.05). The
results of this study further point to the postulated luteotropic function of
prostaglandin E2.
PMID- 25115649
TI - (68)Ga based probe for Alzheimer's disease: synthesis and preclinical evaluation
of homodimeric chalcone in beta-amyloid imaging.
AB - In an attempt to explore use of PET radioisotope, (68)Ga, in the diagnosis of
Alzheimer's disease, a metal-based homodimeric ligand exhibiting high affinity
towards Abeta aggregates was designed by conjugating two chalcone units with the
chelating system, diethylenetriaminepentaacetic acid. Bischalcone derivative, 5,8
bis(carboxymethyl)-13-(4-((E)-3-(4-(dimethylamino)phenyl)acryloyl)phenoxy)-2-(2
(2-(4-((E)-3-(4-(dimethylamino)phenyl)acryloyl)phenoxy)ethylamino)-2-oxoethyl)-10
oxo-2,5,8,11-tetraazatridecane-1-carboxylic acid, DT(Ch)2 was synthesized in 95%
yield with high purity. It was radiolabelled with (68)Ga under mild conditions
with 85.4% efficiency and 9.5-10 MBq nmol(-1) specific activity. An in vitro
binding assay on Abeta42 aggregates displayed high binding affinity of (68)Ga
DT(Ch)2 and inhibition constant of 4.18 +/- 0.62 nM. The fluorescent properties
of the ligand with peaks of absorption/emission at 410/540 nm exhibited a blue
shift with 5.5-fold increase in emission intensity on binding with Abeta
aggregates. Blood kinetics of the complex performed on normal rabbit exhibited
fast clearance (t1/2(F) = 24 +/- 0.08 min; t1/2(S) = 2 h 40 +/- 0.04 min). Ex
vivo biodistribution analysis demonstrated blood-brain barrier penetration with
brain uptake of 1.24 +/- 0.31% ID g(-1) at 2 min p.i. and rapid washout with
negligible activity (0.36% ID g(-1)) left at 30 min p.i. These preliminary
studies reveal that the bivalent approach of synthesis had minimal effect on
binding affinity, signifying that the developed (68)Ga-complex, (68)Ga-DT(Ch)2,
may offer a new perspective in generator produced PET imaging probes for
Alzheimer's disease.
PMID- 25115651
TI - Tracking anti-fibrotic pathways of nilotinib and imatinib in experimentally
induced liver fibrosis: an insight.
AB - The tyrosine kinase inhibitors imatinib and nilotinib have been suggested to have
promising antifibrotic activity in experimental models of liver fibrosis. The aim
of the present study was to investigate new pathways underlying this beneficial
effect. Hepatic injury was induced in male Wistar rats by intraperitoneal
injection of CCl4 for 12 weeks. During the last 8 weeks of treatment, rats were
also injected daily intraperitoneally with 20 mg/kg imatinib or 20, 10 or 5 mg/kg
nilotinib. At the end of treatment, effects on fibrosis were assessed by
measuring serum fibrotic markers and profibrogenic cytokines, as well as by
histopathological examination. Possible anti-inflammatory effects were estimated
by measuring levels of inflammatory cytokines in liver tissue. Liver expression
of alpha-smooth muscle actin, transforming growth factor (TGF)-beta1 antibodies
and platelet-derived growth factor receptor beta (PDGFRbeta) was evaluated by
immunohistochemical staining techniques. Nilotinib (5 and 10 mg/kg) significantly
(P < 0.05) decreased all serum fibrotic markers measured, but 20 mg/kg of either
nilotinib or imatinib had limited effects. At all doses tested, nilotinib
significantly (P < 0.05) decreased the CCl4 -induced increases in tissue
inflammatory cytokines. Furthermore, 5 and 10 mg/kg nilotinib significantly
decreased TGF-beta1 levels and tissue expression of its antibody, as well
expression of PDGFRbeta. In conclusion, low doses (5 and 10 but not 20 mg/kg) of
nilotinib, rather than imatinib, can control hepatic fibrosis by regulating
levels of proinflammatory cytokines, primarily interleukin (IL)-1 and IL-6.
Nilotinib also controls the signalling pathways of profibrogenic cytokines by
lowering TGF-beta1 levels and decreasing expression of PDGFRbeta.
PMID- 25115652
TI - Liquid-based cytology in fine-needle aspiration of breast lesions: a review.
AB - OBJECTIVE: Fine-needle aspiration (FNA) is a safe and cost-effective technique
for the diagnosis of breast lesions, especially when correlated with clinical and
imaging studies. However, the success of breast FNA is highly dependent on the
adequate preparation of cytological conventional smears (CS). The liquid-based
cytology (LBC) technique consists of an automated method for preparing thin-layer
cytological samples from cell suspensions collected in alcohol-based
preservative. LBC is designed to improve CS by avoiding limiting factors such as
obscuring material, air-drying and smearing artifacts. STUDY DESIGN: We performed
a review of the published literature about LBC applied to breast FNA. RESULTS:
LBC preparations of breast aspirates demonstrated better cellular preservation,
less cell overlapping and elimination of blood and excessive inflammation
compared to CS. Conversely, alterations in architecture and cell morphology as
well as loss of myoepithelial cells and stromal elements have been described in
LBC specimens, requiring training before applying this technique for diagnosis.
Studies have shown a similar accuracy between LBC and CS for the diagnosis of
breast lesions. LBC also permits the use of residual material for ancillary
tests, which is an important advantage compared to CS. CONCLUSIONS: LBC can be
safely applied to breast FNA, showing a similar diagnostic accuracy to CS.
PMID- 25115650
TI - Placental FKBP5 genetic and epigenetic variation is associated with infant
neurobehavioral outcomes in the RICHS cohort.
AB - Adverse maternal environments can lead to increased fetal exposure to maternal
cortisol, which can cause infant neurobehavioral deficits. The placenta regulates
fetal cortisol exposure and response, and placental DNA methylation can influence
this function. FK506 binding protein (FKBP5) is a negative regulator of cortisol
response, FKBP5 methylation has been linked to brain morphology and mental
disorder risk, and genetic variation of FKBP5 was associated with post-traumatic
stress disorder in adults. We hypothesized that placental FKBP5 methylation and
genetic variation contribute to gene expression control, and are associated with
infant neurodevelopmental outcomes assessed using the Neonatal Intensive Care
Unit (NICU) Network Neurobehavioral Scales (NNNS). In 509 infants enrolled in the
Rhode Island Child Health Study, placental FKBP5 methylation was measured at
intron 7 using quantitative bisulfite pyrosequencing. Placental FKBP5 mRNA was
measured in a subset of 61 infants by quantitative PCR, and the SNP rs1360780 was
genotyped using a quantitative allelic discrimination assay. Relationships
between methylation, expression and NNNS scores were examined using linear models
adjusted for confounding variables, then logistic models were created to
determine the influence of methylation on membership in high risk groups of
infants. FKBP5 methylation was negatively associated with expression (P = 0.08, r
= -0.22); infants with the TT genotype had higher expression than individuals
with CC and CT genotypes (P = 0.06), and those with CC genotype displayed a
negative relationship between methylation and expression (P = 0.06, r = -0.43).
Infants in the highest quartile of FKBP5 methylation had increased risk of NNNS
high arousal compared to infants in the lowest quartile (OR 2.22, CI 1.07-4.61).
TT genotype infants had increased odds of high NNNS stress abstinence (OR 1.98,
CI 0.92-4.26). Placental FKBP5 methylation reduces expression in a genotype
specific fashion, and genetic variation supersedes this effect. These genetic and
epigenetic differences in expression may alter the placenta's ability to modulate
cortisol response and exposure, leading to altered neurobehavioral outcomes.
PMID- 25115654
TI - Osteoinductive nanohydroxyapatite bone substitute prepared via in situ
hydrothermal transformation of cuttlefish bone.
AB - The capacity to induce a rapid and controlled healing of bone defects is critical
for a bone substitute. Previous studies have reported hydrothermal transformation
(HT) of aragonite from cuttlebone (CB) to cuttlebone hydroxyapatite (CBHA).
However, the biocompatibility and in vivo characteristic of CBHA have not been
fully investigated. We fabricated CBHA via the in situ HT of aragonite from CB.
This CBHA exhibited a highly porous structure and nanoscaled surface morphology
with a significantly higher protein adsorption rate than CB. Marrow mesenchymal
stem cells (MSCs) were seeded and cultured on the CBHA and CB to evaluate their
influence on cell proliferation and differentiation. According to scanning
electronic microscopy observation and MTT assay, the MSCs adhered and
proliferated well on both the CBHA and CB. Compared with the cells on the CB, the
MSCs on CBHA exhibited enhanced alkaline phosphatase activity and osteocalcin
levels after 13 days of culture. In vivo testing revealed that CBHA could induce
ectopic bone formation after implantation, while no bone formation being observed
in the CB. These findings demonstrated that a nanoscaled and osteoinductive bone
substitute could be produced by hydrothermally transforming an aragonite of CB
into a hydroxyapatite.
PMID- 25115655
TI - Trochlear boss height measurement: a comparison of radiographs and MRI.
AB - BACKGROUND: A key anatomical consideration and determinant of surgical approach
in trochlear dysplasia is the trochlear boss height (TBH), traditionally defined
by measurements on plain X-rays (XR). Magnetic resonance (MR) imaging is
increasingly used for pre-operative planning and follow-up. However, it is
unclear whether measurement of TBH on XR is applicable to MR. The aim of this
study was to establish the reliability of TBH measurement on MR compared to XR.
METHODS: This study used lateral knee radiographs and MR scans of 14 knees of
patients with trochlear dysplasia, six knees of non-dysplastic patients with
anterior knee pain (AKP), and five knees of non-dysplastic controls with no AKP.
Correlation between XR and MR measurements was assessed using Pearson correlation
coefficients. Agreement between methods and observers was assessed using Bland
Altman plots with 95% limits of agreement. Intra- and inter-observer reliability
was assessed using intraclass correlation coefficients (ICC). RESULTS: Bland
Altman charts showed a total width of 95% limits of agreement of 4.78 mm for XR
and MR subchondral bone (SB) TBH measurements, and 6.73 mm for XR and MR
cartilage TBH measurements. Inter-observer ICCs were 0.86 for XR, 0.62 for MR SB,
and 0.53 for MR cartilage. The widths of the Bland-Altman 95% limits of agreement
between observers were 4.79 mm (XR), 5.04 mm (MR SB) and 4.74 mm (MR cartilage).
CONCLUSION: Measurement of TBH on MR is not directly interchangeable with XR.
Adjustments need to be made to treatment thresholds based on XR measurement if MR
is used instead.
PMID- 25115656
TI - Root avulsion of the posterior horn of the medial meniscus in skeletally immature
patients.
AB - BACKGROUND: Meniscal root avulsion has been predominantly reported in an adult
population but little is known about this meniscal lesion in children and
adolescents. PURPOSE: The of this article is to describe the clinical symptoms
and a new MRI sign of a medial meniscus posterior root avulsion in skeletally
immature patients, and to report the arthroscopic procedure for its reinsertion
in the presence of open physes. CASE DESCRIPTION: We report two skeletally
immature patients who had a medial meniscus posterior root avulsion [MMPRA].
Diagnosis of a MMPRA was suspected on MRI by intense T2 hypersignal located at
the postero-medial part of the tibial plateau reflecting trabecular bone oedema
("Bone bruise") at the level of the medial meniscal posterior root attachment.
Arthroscopic reduction and fixation of the posterior root of the medial meniscus
with transosseous sutures was performed. The patients returned to sport at the
end of 6 months without residual symptoms. At one year, the radiographs showed no
modification of the physis. Healing of the medial meniscal posterior root was
noted on MRI. CLINICAL RELEVANCE: In a skeletally immature patient it is
important that this rare meniscal lesion is diagnosed early and adequately
treated. We emphasize the importance of the indirect MRI signs that can lead a
clinician to suspect the diagnosis of MMPRA. The aim of the surgery was to
restore the anatomical footprint of the meniscal root and to re-establish its
function thus preventing future chondral damage without damage to the tibial
physeal growth plate. LEVEL OF EVIDENCE: Level IV.
PMID- 25115657
TI - Subclinical hypothyroidism: to treat or not to treat?
PMID- 25115658
TI - Improvement of complex regional pain syndrome after plasmapheresis.
AB - Complex regional pain syndrome is a severe complication following trauma that is
associated with vasomotor, sudomotor and sensory disturbances in an affected limb
or region of the body. The exact physiopathology is not fully understood yet.
Recently, autoantibody findings suggested an immune-mediated physiopathology of
the disease. We here describe two otherwise treatment-resistant patients with
complex regional pain syndrome and high-titre beta2 adrenergic receptor
autoantibodies, who did respond to plasmapheresis. Both patients showed strong
improvement of pain and autonomic symptoms measured by impairment level sum
score.
PMID- 25115659
TI - Histologic evaluation of human pulp tissue after orthodontic intrusion.
AB - INTRODUCTION: The forces applied during orthodontic treatment bring about effects
on the teeth and surrounding tissues. The aim of this study was to evaluate the
possible changes in the human pulpal tissue resulting from orthodontic intrusion
in a 21-day period using histologic examination. METHODS: The sample consisted of
17 young individuals of both sexes between the ages of 12 and 19 years. A total
of 34 premolars were evaluated with orthodontic indication of extraction. Because
it is a split-mouth study, in each patient, intrusion force of 60 g was applied
randomly on 1 of the dental elements experimental group for 21 days. The
counterpart control group received no force. After extractions, these dental
elements were fixed in 10% formaldehyde, processed automatically, submitted to
histotechnical preparation, and stained with hematoxylin-eosin for analysis under
optical microscope. RESULTS: The paired Fisher exact test (P <= .05) showed a
significant increase of fibrous tissue in the experimental group. The
nonparametric paired Wilcoxon test (P <= .05) showed a significant increase in
the number of pulpal nodules in the elements of the experimental group and showed
no difference in the number of blood vessels between the groups. Large-caliber
vessels and congested elements were observed in 8 of the experimental group
elements. CONCLUSIONS: The orthodontic intrusion force, in these conditions,
caused vascular changes in the pulpal tissue and also increased the presence of
fibrosis and the number of pulp calcifications in the experimental elements.
PMID- 25115660
TI - Sealers and warm gutta-percha obturation techniques.
AB - INTRODUCTION: Warm vertically compacted gutta-percha obturation techniques use
root canal sealers that are heated during the obturation. This study aims at
investigating the suitability of selected sealers with warm gutta-percha
obturation techniques. METHODS: The composition of an experimental sealer
(Septodont; Saint Maur-des-Fosses, France), MTA Fillapex (Angelus, Londrina,
Brazil), Apexit Plus (Ivoclar, Schaan, Lichtenstein), and AH Plus (Dentsply
International, Addlestone, UK) was assessed by scanning electron microscopic and
energy-dispersive spectroscopic analysis. The effect of temperature during warm
vertical compaction technique was investigated by testing the sealers' properties
after 1 minute to 100 degrees C or 37 degrees C. The reaction products after
setting were assessed by X-ray diffraction analysis and Fourier transform
infrared spectroscopy. Changes in setting time, flow, and film thickness were
determined using ISO 6876 (2012) specifications. RESULTS: The experimental
tricalcium silicate-based sealer and Apexit Plus contained calcium hydroxide
peaks after setting, which were absent in MTA Fillapex. The properties of AH Plus
and the experimental sealer were modified by heat; the setting time was reduced,
and film thickness increased. AH Plus had diminished N-H groups when heated to
100 degrees C for 1 minute. MTA Fillapex, Septodont sealer, and Apexit Plus were
unaffected by heat application. CONCLUSIONS: The choice of sealer should be
considered when selecting the obturation technique. The Septodont sealer is
recommended for obturations using cold laterally condensed gutta-percha, whereas
MTA Fillapex and Apexit Plus were suitable with warm gutta-percha obturation
techniques.
PMID- 25115661
TI - Unusual morphology of permanent tooth related to traumatic injury: a case report.
AB - INTRODUCTION: Root duplication, or multiple roots, is a very rare anatomy of the
maxillary central incisor. METHODS: This case report describes a permanent
central incisor having 2 distinct roots as an assumed sequela of the avulsion and
replantation of a primary incisor. RESULTS: The permanent successor might have
had a disturbance of development because of the traumatic injury and
discontinuity in the treatment after replantation. Conventional endodontic
treatment followed by esthetic restoration was performed on the tooth.
CONCLUSIONS: Clinicians should consider the potential prognoses and complications
of traumatic injuries to primary teeth.
PMID- 25115662
TI - [Advances in the use of instrumental measurement of colour in the development,
production and quality control of drugs, medicinal preparations and
pharmaceutical auxiliary substances II*].
AB - The paper summarizes the use of instrumental colour measurement in the field of
pharmaceuticals of natural origin and other substances of natural origin
beneficial for health in recent 10 years. Colour measurement in this field was
most frequently employed in the monitoring of various aspects of the process of
drying of medicinal plants and their parts.
PMID- 25115663
TI - [Preparation and evaluation of the oral gel containing the essential oil from
Siberian fir (Abies sibirica Ledeb.)].
AB - Essential oil of the Siberian fir (Abies sibirica Ledeb.) ranks among the
substances with potential use in prevention and treatment of oral candidiasis.
Therefore, the aim of the study was the formulation, preparation and evaluation
of an oral gel containing 0.3% of this essential oil. Carbopol 974P NF in 1%
concentration was used as the gelling agent, some samples were additionally
stabilized by an addition of polysorbate 80 (0.1-0.5%). Xylitol in concentrations
of 10% or 20% was added with the aim to modify the taste properties of the gel.
Following microscopic evaluation (mean oil droplet size, degree of dispersity)
immediately after preparation and after 6-month storage, it has been found that
the optimal concentration of polysorbate 80 is 0.3%. The results of the
experiment also demonstrated that xylitol was not only an excipient adjusting the
organoleptic properties of the preparation - its use enabled significant
improvement of the quality parameters and stability.
PMID- 25115664
TI - [Flavonoids - main constituents of the leaves of Philadelphus tenuifolius Rupr.
et Maxim].
AB - The paper deals with the isolation and identification of the constituents of the
leaves of Philadelphus tenuifolius Rupr. et Maxim. A methanolic extract was used
to isolate quercetin-3-O-glucoside (isoquercitrin), and a butanolic extract to
isolate kaempferol-3-O-glucoside-7-O-rhamnoside. Isolates were identified by
physical-chemical data, comparison with authentic samples and literature data.
The above-mentioned compounds were isolated from Philadelphus tenuifolius Rupr.
et Maxim. for the first time.
PMID- 25115665
TI - [Formulation of benzethonium chloride into gels].
AB - This study is focused on the preparation of gels with antimicrobial effects. A
quaternary ammonium salt, benzethonium chloride, in a concentration of 0.01-0.5%
(w/w) was employed as the drug. The humectant employed was propylene glycol in
concentrations of 5% and 10% (w/w). Two types of polymers, chitosan and
hydroxyethyl cellulose, in the same concentrations of 2.5% (w/w), were used for
gel preparation. Finally the flow properties, rheological parameters and pH
values of the gels were evaluated. Based on the obtained results, the samples of
the gels prepared on the basis of chitosan and hydroxyethyl cellulose, which have
the following optimum composition shown below, were found: 2,5% (w/w) CHIT + 0,5%
(w/w) BZCl + 10% (w/w) PG; 2,5% (w/w) HEC + 0,5% (w/w) BZCl + 5% (w/w) PG.
PMID- 25115666
TI - [Impact of formulation and process parameters on the properties of chitosan-based
microspheres prepared by external ionic gelation].
AB - The aim of this experimental study was to optimize a preparation of microspheres
from high viscosity chitosan by external ion gelation and to evaluate selected
aspects of their preparation. For drug-free microparticles, the concentration of
chitosan dispersions was chosen as a formulation variable; the position of
instrument for a dispersion extrusion (horizontal vs. vertical) was evaluated as
a process variable. On the basis of sphericity and equivalent diameter results,
three different concentrations of chitosan dispersions were used for 5
aminosalicylic acid (5-ASA) encapsulation with the extrusion instrument in
horizontal position, which was considered as the optimal. In consequent drug
loaded microparticle preparation, the influence of the concentration of chitosan
dispersions and composition of hardening solution (10% sodium tripolyphosphate
(TPP) vs. 10% TPP containing drug) was evaluated. In prepared 5-ASA microspheres
it was found that the equivalent diameter increased with increasing chitosan
concentration. In the case of sphericity, significant differences were not found.
Samples prepared with the drug in both chitosan dispersion and hardening solution
had a higher drug content, a smaller equivalent diameter and they showed a faster
in vitro drug release in comparison with the samples prepared with the drug in
chitosan dispersion only.
PMID- 25115667
TI - [Alois Jandouss Czech pharmacopoeial terminology of 1864].
AB - PhMr. Alois Jandous (1838-1893), a Prague pharmacist, laid the foundations of
modern Czech pharmaceutical literature. His first Czech book was a Latin-Czech
dictionary published in 1864. Jandous collected the terms from the 5th edition of
the Austrian Pharmacopoeia. Besides Czech translations of nine hundred Latin
names of pharmaceuticals, it also presented many Czech synonyms and translations
of other technical terms. Though not all of his proposed terms have been
accepted, he has established modern Czech pharmaceutical terminology.
PMID- 25115668
TI - [Rationalization in 20th-century Czechoslovak pharmacy practice - commission for
rationalization and standardization in medicine, veterinary medicine and pharmacy
- part 1].
AB - In the 1920s Czechoslovakia, an increased attention was paid to the new ideas of
scientific management (Taylorism), work rationalization and standardization. This
was reflected in the foundation of the Masaryk Academy of Work in 1920. An effort
to implement the new principles into health care led to the establishment of the
Commission for Rationalization and Standardization in Medicine, Veterinary
Medicine and Pharmacy (RANOK) within the Department of Natural Science and
Medicine of the Academy. Within RANOK, the group for pharmacy worked between 1928
1932. The first part of the paper describes the scientific management and
standardization movement in interwar Czechoslovakia, and the establishment of
Masaryk Academy of Work and RANOK, including the group for pharmacy. The paper
discusses the work objectives of the commission and presents concise biographies
of the group for pharmacy members, too. The second part will be focused on the
work results, relative failure and role of the group. KEYWORDS: Masaryk Academy
of Work Comission for Rationalization and Standardization in Medicine Veterinary
Medicine and Pharmacy (RANOK) work rationalization standardization pharmacy
practice.
PMID- 25115669
TI - Pulmonary embolism in burns, is there an evidence based prophylactic
recommendation? Case report and review of literature.
AB - Burn patients exhibit an acquired hypercoagulable state with increased risk of
venous thromboembolism. Currently, no randomized control study assessing the
efficacy of chemical venous thromboembolism (VTE) prophylaxis in burn patients
has been performed. We present a case of a morbidly (body mass index>54kg/m(2))
obese patient with 18% total body surface area (TBSA) burn who developed a VTE
and a non-fatal submassive pulmonary embolus (PE). We will be reviewing the
current consensus of venous thrombosis prophylaxis in burn patients and briefly
discuss the treatment of PE in this population.
PMID- 25115670
TI - "Banding" esophagus: circumferential bruising due to ligature neck constriction
or circumferential hypostasis due to rapid death?
PMID- 25115671
TI - The applicability of using different energy levels in CT imaging for
differentiation or identification of dental restorative materials.
AB - PURPOSE: The goal of this study was to investigate whether different computed
tomography (CT) energy levels could supply additional information for the
differentiation of dental materials for forensic investigations. METHODS: Nine
different commonly used restorative dental materials were investigated in this
study. A total of 75 human third molars were filled with the restorative dental
materials and then scanned using the forensic reference phantom in singlesource
mode. The mean Hounsfield unit values and standard deviations (SDs) of each
material were calculated at 120, 80 and 140 kVp. RESULTS: Most of the dental
materials could be differentiated at 120 kVp. We found that greater X-ray density
of a material resulted in higher SDs and that the material volume could influence
the measurements. CONCLUSION: Differentiation of dental materials in CT was
possible in many cases using single-energy CT scans at 120 kVp. Because of the
number of dental restorative materials available and scanner and scan parameter
dependence, as well as the CT imaging artifacts, the identification (in contrast
to differentiation) was problematic.
PMID- 25115672
TI - Postmortem wounds caused by cookie-cutter sharks (Isistius species): an autopsy
case of a drowning victim.
PMID- 25115673
TI - Overlaying, co-sleeping, suffocation, and sudden infant death syndrome: the
elephant in the room.
PMID- 25115674
TI - Urinary reconstruction in vertebral, anorectal, cardiac, trachea-esophageal,
renal abnormalities and limb defects association with chronic renal failure and
penile duplication.
AB - Various urological complications in VATER association require careful management.
A 15-year-old boy with VATER association, including a hypoplastic lower urinary
tract and diphallia, presented with chronic kidney disease and incontinence after
a right loop ureterostomy. In order to acquire urinary continence without renal
function impairment, an ileocecal reservoir with umbilical catheterizable stoma
was created as a urinary reconstruction. The ectopic posterior penis was resected
for cosmetic reasons, and the stump of the hypoplastic urethra was opened at the
perineal skin. Clean intermittent self-catheterization through the umbilicus
using disabled bilateral limbs was then achieved. This report describes the
management of VATER association in a patient with complicated urological
anomalies.
PMID- 25115675
TI - Immunization against a merozoite sheddase promotes multiple invasion of red blood
cells and attenuates Plasmodium infection in mice.
AB - BACKGROUND: Subtilisin-like protease 2 (SUB2) is a conserved serine protease
utilized by Plasmodium parasites as a surface sheddase required for successful
merozoite invasion of host red blood cells and has been implicated in ookinete
invasion of the mosquito midgut. To determine if SUB2 is a suitable vaccine
target to interfere with malaria parasite development, the effects of SUB2
immunization on the Plasmodium life cycle were examined in its vertebrate and
invertebrate hosts. METHODS: Swiss Webster mice were immunized with SUB2 peptides
conjugated to Keyhole limpet hemocyanin (KLH) or KLH alone, and then challenged
with Plasmodium berghei. To determine the effects of immunization on parasite
development, infected mice were evaluated by blood film and Giemsa staining. In
addition, collected immune sera were used to perform passive immunization
experiments in non-immunized, P. berghei-infected mice to determine the potential
role of SUB2 in parasite development in the mosquito. RESULTS: Following P.
berghei challenge, SUB2-immunized mice develop a lower parasitaemia and show
improved survival when compared to control immunized mice. Moreover, SUB2
immunization results in an increase in the number of multiply invaded red blood
cells, suggesting that SUB2 antibodies interfere with merozoite invasion. Passive
immunization experiments imply that SUB2 may not have a major role in ookinete
invasion, but this requires further investigation. CONCLUSION: By interfering
with red blood cell invasion, immunization against SUB2 limits malaria parasite
development and confers protection from severe malaria. Together, these results
provide proof-of-principle evidence for future investigation into the use of SUB2
as a vaccine or drug target to interrupt parasite development in more relevant
human malaria models.
PMID- 25115677
TI - Mitochondrial DNA sequence of Lampetra morri.
AB - Lampetra morri belongs to the Petromyzontidae family. It is one of the most
important freshwater aquaculture species in China. In this study, the complete
sequence of mitochondrial genome of L. morri was 16,451 base pair, including 13
protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 2 repeat
regions. The percentage of G + C content was 39.33%. This is the first time of
the mitochondrial genome of L. morri being sequenced, and it provides insights
into the evolution of Cyclostomata mitochondrial genomes, particular in Lampetra
family.
PMID- 25115678
TI - The complete mitochondrial genome of Saurida umeyoshii (Aulopiformes:
Synodontidae).
AB - In this study, the complete mitochondrial genome (mitogenome) sequence of Saurida
umeyoshii has been determined by long polymerase chain reaction and primer
walking methods. The complete mitochondrial genome is 16,546 bp in length and
contains 37 mitochondrial genes (13 protein-coding genes, 2 ribosomal RNA (rRNA),
22 transfer RNA (tRNA)), and a control region as other bony fishes. Within the
control region, we identified the termination-associated sequence domain (TAS),
the central conserved sequence block domains (CSB-F, CSB-E, CSB-D, CSB-C, CSB-B
and CSB-A), and the conserved sequence block domains (CSB-1, CSB-2 and CSB-3).
PMID- 25115676
TI - Single-walled carbon nanotubes alleviate autophagic/lysosomal defects in primary
glia from a mouse model of Alzheimer's disease.
AB - Defective autophagy in Alzheimer's disease (AD) promotes disease progression in
diverse ways. Here, we demonstrate impaired autophagy flux in primary glial cells
derived from CRND8 mice that overexpress mutant amyloid precursor protein (APP).
Functionalized single-walled carbon nanotubes (SWNT) restored normal autophagy by
reversing abnormal activation of mTOR signaling and deficits in lysosomal
proteolysis, thereby facilitating elimination of autophagic substrates. These
findings suggest SWNT as a novel neuroprotective approach to AD therapy.
PMID- 25115683
TI - Trends in prevalence and treatment of ocular allergy.
AB - PURPOSE OF REVIEW: This review describes recent findings and trends in prevalence
and treatment of allergic ocular diseases. Although the major focus is on
seasonal and perennial allergic conjunctivitis, related disorders will also be
considered. RECENT FINDINGS: Published reports from countries around the world
suggest that the spectrum of atopic diseases, including seasonal and perennial
allergic conjunctivitis, is continuing its pattern of increasing prevalence,
which has been well documented over the past few decades. In addition, although
treatment modalities have focused on topical formulations including
antihistamines and corticosteroids, there is a significant emphasis on
immunotherapy as an alternative treatment modality, particularly in the USA.
SUMMARY: Allergic conjunctivitis is a key component in the spectrum of allergic
diseases that is sometimes collectively referred to as rhinoconjunctivitis.
Because of its high prevalence worldwide, it exacts an increasing toll in terms
of patient discomfort, morbidity, and loss of productivity. Current estimates
suggest that at least 20% of the overall population suffers from some form of
allergic conjunctivitis, many without ever seeking treatments. In addition, a
significant proportion of patients experience chronic forms of allergy that are
less responsive to existing therapies. Recent approval of immunotherapy-based
treatments may address this therapeutic gap.
PMID- 25115684
TI - Update on house dust mite immunotherapy: are more studies needed?
AB - PURPOSE OF REVIEW: Although systematic reviews have confirmed the effectiveness
of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) for the
treatment of allergic rhinitis and allergic asthma, a review of studies employing
extracts of house dust mites (HDMs) for immunotherapy found no consensus on basic
treatment parameters. RECENT FINDINGS: Over the last 2 years nine additional
reports on immunotherapy with HDM extract preparations have been published. Six
studies were with SLIT, five for allergic rhinitis and one for allergic asthma.
The other three studies were all with SCIT in children with allergic asthma.
SUMMARY: The publication of these nine studies supports the efficacy of HDM-SLIT
for allergic rhinitis and asthma and for HDM-SCIT for asthma in children. The
reported safety data are also reassuring, especially for SLIT.HDM-SLIT tablets
under development will have optimal doses established in large, randomized,
placebo-controlled trials. The HDM-SCIT trial in children with allergic asthma
confirms the efficacy of a commercialized HDM preparation for injection
immunotherapy. However, the information that is presented on dosing in the
articles on SLIT-liquid is unsatisfactory, as doses are not presented in a form
that the clinician can use to guide their practice.
PMID- 25115682
TI - Type-2 innate lymphoid cells in human allergic disease.
AB - PURPOSE OF REVIEW: Recent decades have seen allergic diseases become endemic in a
number of developed countries. Understanding the inflammatory processes that
dictate these allergic responses is therefore important. RECENT FINDINGS:
Critical to many allergic responses is the inappropriate release of the type-2
immune-regulatory cytokines: interleukin-4, interleukin-5, interleukin-9, and
interleukin-13. The study of these inflammatory mediators has led directly to the
development of two new asthma treatments: anti-interleukin-5 and anti-interleukin
13. Until recently, T helper 2 cells were considered to be the major cellular
source of type-2 cytokines; however, a paradigm shift occurred with the discovery
of a novel population, type-2 innate lymphoid cells (ILC2s), that can produce
huge levels of type-2 cytokines and are sufficient to induce allergy in mice.
This discovery raises interesting questions about how innate and adaptive type-2
immunity might interact to induce relapsing and remitting episodes of allergy in
patients. SUMMARY: It is essential that alongside the mechanistic investigation
using model organisms, the roles of ILC2s in human disease be explored. Here, we
discuss how ILC2 traits, discovered in mouse models, have informed research in
humans and how newly identified human ILC2 pathways might provide potential
therapeutic benefits in the future.
PMID- 25115685
TI - Specific immunotherapy and biological treatments for occupational allergy.
AB - PURPOSE OF REVIEW: Occupational allergy represents a substantial health, social,
and financial burden for the society. Its management is a complex task that, in
selected cases, may also include allergen-specific immunotherapy. The purpose of
this article is to review clinical data on allergen immunotherapy and biological
treatments applied to occupational allergy in 2013. RECENT FINDINGS:
Immunotherapy in occupational allergic diseases has been scarcely used, and only
for a few sensitizers, such as latex, flour, and Hymenoptera venom, partly due to
the lack of standardized extracts. The recent use of the molecular diagnosis can
improve the indication and selection of suitable allergens for preparing new
standardized and powerful extracts for immunotherapy. Some recent reports suggest
a beneficial role of treatment with omalizumab in workers with occupational
asthma who continue to be exposed to the causal agent. SUMMARY: Although scarce,
available data suggest that immunotherapy and biological treatments may allow
allergic workers to continue their work activity, but further studies are needed
to standardize extracts and to evaluate the cost-effectiveness of these
treatments, when exposure at the workplace cannot be avoided.
PMID- 25115687
TI - Supercritical CO2 extraction of volatile oils from Sardinian Foeniculum vulgare
ssp. vulgare (Apiaceae): chemical composition and biological activity.
AB - This article reports the results on the composition and antifungal effect of
volatile extracts obtained from the aerial parts of Sardinian wild fennel
(Foeniculum vulgare Mill.), by supercritical fluid extraction (SFE) and by
hydrodistillation (HD). The extracts were analysed by gas chromatography-mass
spectrometry for qualitative composition and gas chromatography-flame ionisation
detector to establish the percentage of constituents. The main components were
fenchone (7.1% vs. 8.8%), estragole (34.9% vs. 42.6%) and (E)-anethole (24.6% vs.
43.4%) in the SFE and HD extract, respectively. Minimum inhibitory concentrations
(MICs) were measured according to the reference Clinical and Laboratory Standards
Institute (CLSI) broth macrodilution protocols. Minimum lethal concentrations
were determined by subsequent subculturing of the same cell suspensions in solid
medium. The essential oil was more active against Candida albicans, whereas the
supercritical fluid extract possesses higher activity against Candida
guillermondii and Cryptococcus neoformans, with MIC values of 0.32 MUL/mL.
PMID- 25115686
TI - A pilot clinical study of resveratrol in postmenopausal women with high body mass
index: effects on systemic sex steroid hormones.
AB - BACKGROUND: Breast cancer risk is partially determined by several hormone-related
factors. Preclinical and clinical studies suggested that resveratrol may modulate
these hormonal factors. METHODS: We conducted a pilot study in postmenopausal
women with high body mass index (BMI >= 25 kg/m2) to determine the clinical
effect of resveratrol on systemic sex steroid hormones. Forty subjects initiated
the resveratrol intervention (1 gm daily for 12 weeks) with six withdrawn early
due to adverse events (AEs). Thirty-four subjects completed the intervention.
RESULTS: Resveratrol intervention did not result in significant changes in serum
concentrations of estradiol, estrone, and testosterone but led to an average of
10% increase in the concentrations of sex steroid hormone binding globulin
(SHBG). Resveratrol intervention resulted in an average of 73% increase in
urinary 2-hydroxyestrone (2-OHE1) levels leading to a favorable change in urinary
2-OHE1/16alpha-OHE1 ratio. One participant had asymptomatic Grade 4 elevation of
liver enzymes at the end of study intervention. Two subjects had Grade 3 skin
rashes. The remaining adverse events were Grade 1 or 2 events. The most common
adverse events were diarrhea and increased total cholesterol, reported in 30% and
27.5% of the subjects, respectively. CONCLUSION: We conclude that among
overweight and obese postmenopausal women, daily 1 gm dose of resveratrol has
favorable effects on estrogen metabolism and SHBG. Further placebo-controlled
studies are needed to confirm our findings on these hormone-related breast cancer
risk factors and the attribution of the adverse effects observed in the study
population. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01370889.
PMID- 25115689
TI - Is it possible to predict urodynamic stress urinary incontinence in women with
minimal diagnostic evaluation?
AB - OBJECTIVES: To determine whether it is possible to predict urodynamic stress
urinary incontinence (uSUI) in women with minimal diagnostic evaluation.
MATERIALS AND METHODS: Medical records of 2,643 female incontinent patients were
reviewed and 301 women were eligible for this study. The positive predictive
values (PPV), sensitivity, specificity and negative predictive values (NPV) for
uSUI and uSUI with or without detrusor overactivity (DO), and DO patients of pure
SUI symptom (group 1), combination of pure SUI symptom and positive provocative
stress test (+PST; group 2) and combination of pure SUI symptom, +PST and absence
of overactive bladder symptoms (group 3) were calculated for each group. RESULTS:
Mean age was 51.03 years (22-88). PPV, sensitivity and specificity values for
uSUI with or without DO of group 3 were 100, 7.4, and 100%, while these values
for pure uSUI were 93.3, 9.3, and 99.3%, respectively. Interestingly, none of the
patients in groups 2 and 3 had DO. CONCLUSIONS: Our results show that it was
possible to predict uSUI with high accuracy using minimal diagnostic evaluation
in a group of female patients with pure stress incontinence symptoms +PST while
it was also possible to eliminate DO accurately in this group of patients.
PMID- 25115688
TI - Predictors of hoarding severity in older adults with hoarding disorder.
AB - BACKGROUND: The recent addition of hoarding disorder (HD) to the Diagnostic and
Statistical Manual of Mental Health Disorders, 5th edition, has highlighted the
dearth of information about the demographic, sociologic, and medical predictors
of HD severity, particularly in older adults. Although there have been several
previous studies examining the characteristics of older adults with HD, and one
investigation of psychiatric correlates of hoarding symptom severity in non
clinical older adults, there has been little investigation about which
characteristics predict hoarding symptom severity in older adults with HD.
METHODS: Participants were 71 older adults who were enrolled for one of the two
studies of HD at the VA San Diego Healthcare System between January 2010 and
January 2014. RESULTS: There were multiple differences in the predictive ability
of patient characteristics between the more cognition-related symptoms of HD and
the more concrete measure of clutter, including gender-based differences and
anxiety severity. Further, married participants were more likely to report lower
hoarding severity, and there was no significant relationship between hoarding
severity and intervention attempts or hoarding and reported falls in the past
three years. CONCLUSIONS: Multiple predictive factors have been presented, which
may result in further studies to investigate possible predictive differences in
cognition and clutter symptoms of HD. Future studies should examine the
possibility of the predictive factors also identified to be moderators of
treatment outcomes.
PMID- 25115690
TI - Electron-phonon coupling in quantum-well states of the Pb/Si(1 1 1) system.
AB - The electron-phonon coupling parameters in the vicinity of the Gamma point,
lambda(Gamma), for electronic quantum well states in epitaxial lead films on a
Si(1 1 1) substrate are measured using 5, 7 and 12 ML films and femtosecond laser
photoemission spectroscopy. The lambda (Gamma) values in the range of 0.6-0.9
were obtained by temperature-dependent line width analysis of occupied quantum
well states and found to be considerably smaller than the momentum averaged
electron-phonon coupling at the Fermi level of bulk lead, (lambda = 1.1-1.7). The
results are compared to density functional theory calculations of the lead films
with and without interfacial stress. It is shown that the discrepancy can not be
explained by means of confinement effects or simple structural modifications of
the Pb films and, thus, is attributed to the influence of the substrate on the Pb
electronic and vibrational structures.
PMID- 25115691
TI - Selection of proper reference genes for the cyanobacterium Synechococcus PCC 7002
using real-time quantitative PCR.
AB - Synechococcus sp. PCC 7002 is known to be tolerant to most of the environmental
factors in natural habitats of Cyanobacteria. Gene expression can be easily
studied in this cyanobacterium, as its complete genome sequence is available.
These properties make Synechococcus sp. PCC 7002 an appropriate model organism
for biotechnological applications. To study the gene expression in Cyanobacteria,
real-time quantitative PCR (qPCR) can be used, but as this is a highly sensitive
method, data standardization is indicated between samples. The most commonly used
strategy is normalization against internal reference genes. Synechococcus sp. PCC
7002 has not yet been evaluated for the best reference genes. In this work, six
candidate genes were analyzed for this purpose. Cyanobacterial cultures were
exposed to several stress conditions, and three different algorithms were used
for ranking the reference genes: geNorm, NormFinder, and BestKeeper. Moreover,
gene expression stability value M and single-control normalization error E were
calculated. Our data provided a list of reference genes that can be used in qPCR
experiments in Synechococcus sp. PCC 7002.
PMID- 25115695
TI - Adrenoceptor Polymorphisms in Hypertension and Diabetes with obesity-update in
2014.
AB - Hypertension, diabetes mellitus (especially type 2 diabetes mellitus) and
metabolic syndrome associated with obesity are rapidly growing public health
problems. Sympathetic nerve activation is well documented in hypertension,
diabetes mellitus, and obesity, hypertension and diabetes are determined by
genetic background and environmental factors. Reduced energy expenditure and
resting metabolic rate are predictive of weight gain, and the sympathetic nervous
system participates in regulating energy balance through thermogenesis. The
thermogenic effects of sympathetic nervous system in obesity have been mainly
mediated via the beta2 and beta3-adrenergic receptors in humans. Further, beta2
adrenoceptors importantly influence vascular reactivity and may regulate blood
pressure. Genetic polymorphisms of the ?-adrenoceptor gene have been shown to
alter the function of several adrenoceptor subtype and thus to modify the
response to catecholamine. Among beta2-adrenoceptor polymorphisms, Arg16Gly,
Gln27Glu, and Thr164Ile are considered the most functionally important. beta2
adrenoceptor genes have been studied in relation to hypertension. Genetic
variations in the beta3-adrenoceptor, such as the Try64Arg variant, are also
associated with both obesity and hypertension. This review is an update of
several versions published of the relationships between adrenoceptor
polymorphisms and hypertension, diabetes and obesiy based on the my own review on
the relationship with obesity in 2011 in "Journal of Obesity" [1], and another of
my own reviews on the relationships with hypertension in 2010 in "International
journal of Hypertension" [2], with 37 articles provided by the "PubMed" with the
keywords of "adrenoceptor polymorphisms, obesity, hypertension and diabetes"
searched on December 2013. However, the relationships of the polymorphisms of
beta2- and beta3-adrenoceptor genes with sympathetic nervous system activity,
hypertension and metabolic syndrome have been still discordant, it might be
related to the ethnicity, gender, severeity of obesity, duration of hypertension
or obesity, etc (refer the "Possible confounding variable affecting the
relationships" section and Table 4). Therefore, this review may not be so much
different from the previous ones, but, of importance, currently most
investigations have shown that the beta-adrenoceptor polymorphisms accompanying
sympathetic nervous activity contribute to the onset and maintenance of
hypertension, diabetes and obesity.
PMID- 25115693
TI - Cooperative hybridization of gammaPNA miniprobes to a repeating sequence motif
and application to telomere analysis.
AB - GammaPNA oligomers having one or two repeats of the sequence AATCCC were designed
to hybridize to DNA having one or more repeats of the complementary TTAGGG
sequence found in the human telomere. UV melting curves and surface plasmon
resonance experiments demonstrate high affinity and cooperativity for
hybridization of these miniprobes to DNA having multiple complementary repeats.
Fluorescence spectroscopy for Cy3-labeled miniprobes demonstrate increases in
fluorescence intensity for assembling multiple short probes on a DNA target
compared with fewer longer probes. The fluorescent gammaPNA miniprobes were then
used to stain telomeres in metaphase chromosomes derived from U2OS cells
possessing heterogeneous long telomeres and Jurkat cells harboring homogenous
short telomeres. The miniprobes yielded comparable fluorescence intensity to a
commercially available PNA 18mer probe in U2OS cells, but significantly brighter
fluorescence was observed for telomeres in Jurkat cells. These results suggest
that gammaPNA miniprobes can be effective telomere-staining reagents with
applications toward analysis of critically short telomeres, which have been
implicated in a range of human diseases.
PMID- 25115696
TI - Blood Pressure Variability/Dipper/Non-dipper in Hypertension and Diabetes.
AB - It has been well recognized that hypertension in diabetes is a potent risk of
micro- and macrovascular complications. BP levels are most important component of
BP management. Next to BP levels, other component such as BP variability is also
important. BP variability consists of several concepts [1]
1) Very Short
term BP variability (beat-to-beat)
2) Short term BP variability (over the
24h)
3) Diurnal BP variation in diabetes
4) Long term BP
variability (day-by-day)
5) Visit-to-Visit Variability (months ~ years)
Among these, abnormal circadian rhythm of BP belongs to short-term BP
variability. There have been a number of papers about BP variability in recent
years. In this chapter, the significance of BP variability in patients with
diabetes will be reviewed.
PMID- 25115697
TI - Role of Renin-Angiotensin-Aldosterone System in Metabolic Syndrome and Obesity
related Hypertension.
AB - Several recent clinical trials show that blocking agents of the renin-angiotensin
aldosterone system (RAAS) reduce cardiovascular events in patients with metabolic
syndrome based on insulin resistance and obesity, especially accumulated visceral
fat. Our laboratory has focused on the relationship between the vascular RAAS and
the action of insulin on the vasculature. We first revealed that the addition of
insulin to cultured vascular smooth muscle cells (VSMC) markedly increases
angiotensinogen and angiotensin II (Ang II) expression and production. Insulin
addition also induces VSMC growth that is inhibited by the blockade of the RAAS
by either ACEI or ARB which suggests a role for the RAAS in insulin-mediated
growth. Insulin has a quite different effect on cultured vascular endothelial
cells (EC) as it reduces angiotensinogen and renin expression. However, insulin
added to EC induces a marked activation of ACE and the activated ACE promotes the
conversion of Ang I to Ang II and cell growth under conditions of high insulin
concentration. Ang II induces the progression of atherosclerosis through the
production of oxidative stress that blocks insulin signaling and accelerates
atherosclerosis. In this paper, we attempt to clarify the relationship between
insulin resistance, the RAAS, and oxidative stress in vascular tissues to mimic
in vivo conditions found in patients with metabolic syndrome and obesity-related
hypertension as previously I reviewed in "Current Hypertension Reviews" in 2010
[1]. In addition, I update the relationships between vascular RAAS and insulin
resistance for the last 4 years. JSH-2014 [2] states that the target goals of
blood pressure (BP) for diabetes patients is lower than 130/80 mmHg, whereas
updated JNC 8 [3] and ESH-ESC 2013 [4] recommends the target BP was changed to
<140/90 mmHg for hypertensive patients with diabetes. Patients with diabetes and
hypertension have reduced mortality as well as improved cardiovascular and
cerebrovascular outcomes with treatment to a goal SBP <150 mm Hg, but no
randomized controlled trials support a goal <140/90 mm Hg. Despite this, the
panel opted for a conservative recommendation in patients with diabetes and
hypertension, opting for a goal level of <140/90 mm Hg in adult patients with
diabetes and hypertension rather than the evidence based goal of <150/90 mm Hg
[3, 5]. JSH-2014 recommends that the first choice of antihypertensive medication
should be RAAS blockers such as ACE inhibitor or ARB. For the last several years,
several large cohort clinical studies using ACEI and ARB have shown more
favorable effects, but aldosterone receptor inhibitor (mineral corticoid receptor
inhibitors; MR inhibitors) and Renin Inhibitors have been withdrawn. Some studies
showed the strong support to use these medications for diabetic patients. This
review will discuss the relationships between vascular RAAS and insulin
resistance in patients with hypertension and diabetes as previously reviewed with
new updated findings for the last 4 years, and clinical implications based on
updated JNC-8, ESH-ESC2013 and JSH-2014.
PMID- 25115694
TI - Stomach cancer mortality among workers exposed to asbestos: a meta-analysis.
AB - BACKGROUND: The relationship between asbestos and stomach cancer is not well
understood because of small number of cases. This study aimed to determine the
incidence and mortality of stomach cancer among workers exposed to asbestos based
on a systematic review and meta-analysis approach. METHODS: Relevant English
electronic databases were systematically searched for published studies
characterizing the risk of developing stomach cancer as a result of asbestos
exposure. Standardized mortality rate (SMR) for stomach cancer with its 95%
confidence interval (CI) was pooled using a fixed-/random-effect model in STATA.
RESULTS: A total of 32 independent studies were included for the analysis. The
overall SMR for stomach cancer was 1.19 (95% CI 1.06-1.34), with a moderate
degree of heterogeneity across the studies (I(2) = 37.6%, P = 0.011). Being male,
exposure to crocidolite, miners, studies conducted in Europe and Oceania, and
long study follow-up (>= 25 years) all contribute to significantly higher SMR.
Significant publication bias was observed. CONCLUSION: Elevated risk of stomach
cancer mortality was evidenced among workers exposed to crocidolite, especially
male miners.
PMID- 25115692
TI - Recent progress in gastric arrhythmia: pathophysiology, clinical significance and
future horizons.
AB - Gastric arrhythmia continues to be of uncertain diagnostic and therapeutic
significance. However, recent progress has been substantial, with technical
advances, theoretical insights and experimental discoveries offering new
translational opportunities. The discoveries that interstitial cells of Cajal
(ICC) generate slow waves and that ICC defects are associated with dysmotility
have reinvigorated gastric arrhythmia research. Increasing evidence now suggests
that ICC depletion and damage, network disruption and channelopathies may lead to
aberrant slow wave initiation and conduction. Histological and high-resolution
(HR) electrical mapping studies have now redefined the human 'gastric conduction
system', providing an improved baseline for arrhythmia research. The application
of HR mapping to arrhythmia has also generated important new insights into the
spatiotemporal dynamics of arrhythmia onset and maintenance, resulting in the
emergence of new provisional classification schemes. Meanwhile, the strong
associations between gastric functional disorders and electrogastrography (EGG)
abnormalities (e.g. in gastroparesis, unexplained nausea and vomiting and
functional dyspepsia) continue to motivate deeper inquiries into the nature and
causes of gastrointestinal arrhythmias. In future, technical progress in EGG
methods, new HR mapping devices and software, wireless slow wave acquisition
systems and improved gastric pacing devices may achieve validated applications in
clinical practice. Neurohormonal factors in arrhythmogenesis also continue to be
elucidated and a deepening understanding of these mechanisms may open
opportunities for drug design for treating arrhythmias. However, for all
translational goals, it remains to be seen whether arrhythmia can be corrected in
a way that meaningfully improves organ function and symptoms in patients.
PMID- 25115698
TI - Role of the sympathetic nervous activity in hypertension-update in 2014.
AB - Many reviews focused on the role of sympathetic nervous activity in hypertension
have been published. Recently a new treatment, radiofrequency renal denervation
for the treatment of resistant hypertension has been developed and examined in
several clinical trials such as the Symplicity HTN and EnligHTN studies. In the
Symplicity HTN-1 study the efficacy for lowering blood pressure remained
satisfactory at 3 years follow up and many ancillary ameliorative effects have
been reported including cardiovascular, psychosocial, and metabolic effects. The
purpose of this review is to provide the current findings on the relationships
between sympathetic nerve activity and hypertension, especially focus on the
importance of renal sympathetic nervous activity for the onset and development of
hypertension. In addition, the methods to assess sympathetic nervous activity are
reviewed.
The renal denervastion was developed for the treatment
resistant hypertensive patients, and excessive confidence of the efficacy and
safety existed by the end of 2013, although several issues on the efficacy and
safety were reported in 2014. Furthermore, long-term efficacy and impact on renal
function have been unclear. Those issues have to be clear for clinical usage.
This review will also address the recent data from the renal denervation.
PMID- 25115699
TI - An efficient CeO2 /CoSe2 Nanobelt composite for electrochemical water oxidation.
AB - CeO2 /CoSe2 nanobelt composite for electrochemical water oxidation: A new CeO2
/CoSe2 nanobelt composite is developed as a highly effective water oxidation
electrocatalyst by growing CeO2 nanoparticle CoSe2 nanobelts in situ via a simple
polyol reduction route. The constructed hybrid catalyst shows extremely high
oxgen evolution reaction (OER) activity, even beyond the state-of-the-art RuO2
catalyst in alkaline media.
PMID- 25115700
TI - Endoperoxide polyketides from a Chinese Plakortis simplex: further evidence of
the impact of stereochemistry on antimalarial activity of simple 1,2-dioxanes.
AB - Chemical investigation of the organic extract obtained from the sponge Plakortis
simplex collected in the South China Sea afforded five new polyketide
endoperoxides (2 and 4-7), along with two known analogues (1 and 3). The
stereostructures of these metabolites have been deduced on the basis of
spectroscopic analysis and chemical conversion. The isolated endoperoxide
derivatives have been tested for their in vitro antimalarial activity against
Plasmodium falciparum strains, showing IC50 values in the low micromolar range.
The structure-activity relationships were analyzed by means of a detailed
computational investigation and rationalized in the light of the mechanism of
action proposed for this class of simple antimalarials. The relative orientation
of the atoms involved in the putative radical generation and transfer reaction
was demonstrated to have a great impact on the antimalarial activity. The
resulting 3D pharmacophoric model can be a useful guide to design simple and
effective antimalarial lead compounds belonging to the class of 1,2-dioxanes.
PMID- 25115701
TI - A designed conformational shift to control protein binding specificity.
AB - In a conformational selection scenario, manipulating the populations of binding
competent states should be expected to affect protein binding. We demonstrate how
in silico designed point mutations within the core of ubiquitin, remote from the
binding interface, change the binding specificity by shifting the conformational
equilibrium of the ground-state ensemble between open and closed substates that
have a similar population in the wild-type protein. Binding affinities determined
by NMR titration experiments agree with the predictions, thereby showing that,
indeed, a shift in the conformational equilibrium enables us to alter ubiquitin's
binding specificity and hence its function. Thus, we present a novel route
towards designing specific binding by a conformational shift through exploiting
the fact that conformational selection depends on the concentration of binding
competent substates.
PMID- 25115703
TI - The adhesive potential of dentin bonding systems assessed using cuspal deflection
measurements and cervical microleakage scores.
AB - OBJECTIVES: To assess the cuspal deflection and cervical microleakage of
standardized mesio-occluso-distal (MOD) cavities restored with a dimethacrylate
resin-based-composite (RBC) placed with one 3-step, one 2-step and three 1-step
bonding systems and compared with the unbound condition. METHODS: Forty-eight
sound maxillary premolar teeth with standardized MOD cavities were randomly
allocated to six groups. Restoration was performed in eight oblique increments
using a quartz-tungsten-halogen (QTH) light curing unit (LCU) with the bonding
condition as the dependent variable. Buccal and palatal cuspal deflections were
recorded post-irradiation using a twin channel deflection measuring gauge at 0,
30, 60 and 180s. Following restoration, the teeth were thermocycled, immersed in
a 0.2% basic fuchsin dye for 24h, sectioned and examined for cervical
microleakage assessment. RESULTS: The mean total cuspal deflection measurements
with the one 3-step, one 2-step and three 1-step bonding systems were 11.26
(2.56), 10.95 (2.16), 10.03 (2.05) (Futurabond((r)) DC SingleDose), 6.37 (1.37)
(AdperTM PromptTM L-PopTM), 8.98 (1.34) MUm (All-Bond SE((r))), respectively when
compared with the unbound condition (6.46 (1.88) MUm) The one-way ANOVA of the
total cuspal deflection measurements identified statistical differences (p<0.001)
between groups. Cervical microleakage scores significantly increased (p<0.001)
for the negative control (unbound condition) when compared with teeth restored
with a bonding system although differences between the bonding systems were
evident (p<0.001). SIGNIFICANCE: The cuspal deflection and cervical microleakage
protocol reported offers an opportunity to test the bonding technologies
available to practitioners for RBCs. Poorly performing adhesives can be
identified which indicated the technique may be useful as a screening tool for
assessing existing and new bonding technologies which offers the potential to
limit complications routinely encountered with Class II RBC restorations.
PMID- 25115702
TI - Structure of a stapled peptide antagonist bound to nutlin-resistant Mdm2.
AB - As key negative regulator of the p53 tumour suppressor, Mdm2 is an attractive
therapeutic target. Small molecules such as Nutlin have been developed to
antagonise Mdm2, resulting in p53-dependent death of tumour cells. We have
recently described a mutation in Mdm2 (M62A), which precludes binding of Nutlin,
but not p53. This Nutlin-resistant variant is not, however, refractory to binding
and inhibition by stapled peptide antagonists targeting the same region of Mdm2.
A detailed understanding of how stapled peptides are recalcitrant to Mdm2
mutations conferring Nutlin-resistance will aid in the further development of
potent Mdm2 antagonists. Here, we report the 2.00 A crystal structure of a
stapled peptide antagonist bound to Nutlin resistant Mdm2. The stapled peptide
relies on an extended network of interactions along the hydrophobic binding cleft
of Mdm2 for high affinity binding. Additionally, as seen in other stapled peptide
structures, the hydrocarbon staple itself contributes to binding through
favourable interactions with Mdm2. The structure highlights the intrinsic
plasticity present in both Mdm2 and the hydrocarbon staple moiety, and can be
used to guide future iterations of both small molecules and stapled peptides for
improved antagonists of Mdm2.
PMID- 25115704
TI - Effect of different surface treatments on the hydrothermal degradation of a 3Y
TZP ceramic for dental implants.
AB - OBJECTIVES: Implant surface modifications are intended to enhance bone
integration. The objective of this study was to assess the effect of different
surface treatments on the resistance to hydrothermal degradation, hardness and
elastic modulus of a 3Y-TZP ceramic used for dental implants. METHODS: Samples
grouped according to their surface morphologies (AS, as-sintered; C, coated; P,
dry-polished; R, roughened; PA, polished and annealed; RA, roughened and
annealed) were subjected to accelerated hydrothermal degradation (LTD) by
exposure to water steam (134 degrees C, 2bars) for 100h. The t-m phase
transformation was quantified by grazing incidence X-ray diffraction (GIXDR) and
by combined focused ion beam and scanning electron microscopy (FIB-SEM). Elastic
modulus and hardness before- and after prolonged aging (100h) were assessed by
nanoindentation. RESULTS: AS and C specimens presented a better resistance to
hydrothermal degradation than P and R samples. After prolonged aging, the depth
of the monoclinic transformed layer ranged from 11MUm to 14MUm. Hydrothermal
degradation led to a significant decrease of elastic modulus and hardness.
SIGNIFICANCE: Surface treatments affected the resistance to hydrothermal
degradation of the 3Y-TZP ceramic. Dry mechanical surface modifications should be
avoided since a high t-m transformation rate associated to the initial monoclinic
content was observed. Annealing was useful to reverse the initial t-m
transformation, but did not improve the resistance to hydrothermal degradation.
PMID- 25115707
TI - Editorial Comment from Dr Li to Is the presence of varicocele associated with
static and dynamic components of benign prostatic hyperplasia/lower urinary tract
symptoms in elderly men?
PMID- 25115706
TI - Figmop: a profile HMM to identify genes and bypass troublesome gene models in
draft genomes.
AB - MOTIVATION: Gene models from draft genome assemblies of metazoan species are
often incorrect, missing exons or entire genes, particularly for large gene
families. Consequently, labour-intensive manual curation is often necessary. We
present Figmop (Finding Genes using Motif Patterns) to help with the manual
curation of gene families in draft genome assemblies. The program uses a pattern
of short sequence motifs to identify putative genes directly from the genome
sequence. Using a large gene family as a test case, Figmop was found to be more
sensitive and specific than a BLAST-based approach. The visualization used allows
the validation of potential genes to be carried out quickly and easily, saving
hours if not days from an analysis. AVAILABILITY AND IMPLEMENTATION: Source code
of Figmop is freely available for download at https://github.com/dave-the
scientist, implemented in C and Python and is supported on Linux, Unix and
MacOSX. CONTACT: curran.dave.m@gmail.com SUPPLEMENTARY INFORMATION: Supplementary
data are available at Bioinformatics online.
PMID- 25115705
TI - Modeling dynamic functional relationship networks and application to ex vivo
human erythroid differentiation.
AB - MOTIVATION: Functional relationship networks, which summarize the probability of
co-functionality between any two genes in the genome, could complement the
reductionist focus of modern biology for understanding diverse biological
processes in an organism. One major limitation of the current networks is that
they are static, while one might expect functional relationships to consistently
reprogram during the differentiation of a cell lineage. To address this potential
limitation, we developed a novel algorithm that leverages both differentiation
stage-specific expression data and large-scale heterogeneous functional genomic
data to model such dynamic changes. We then applied this algorithm to the time
course RNA-Seq data we collected for ex vivo human erythroid cell
differentiation. RESULTS: Through computational cross-validation and literature
validation, we show that the resulting networks correctly predict the (de)
activated functional connections between genes during erythropoiesis. We
identified known critical genes, such as HBD and GATA1, and functional
connections during erythropoiesis using these dynamic networks, while the
traditional static network was not able to provide such information. Furthermore,
by comparing the static and the dynamic networks, we identified novel genes (such
as OSBP2 and PDZK1IP1) that are potential drivers of erythroid cell
differentiation. This novel method of modeling dynamic networks is applicable to
other differentiation processes where time-course genome-scale expression data
are available, and should assist in generating greater understanding of the
functional dynamics at play across the genome during development. AVAILABILITY
AND IMPLEMENTATION: The network described in this article is available at
http://guanlab.ccmb.med.umich.edu/stageSpecificNetwork.
PMID- 25115708
TI - The regulation of Sox2 and Sox9 stimulated by ATP in spinal cord astrocytes.
AB - After spinal cord injury (SCI), the level of adenosine triphosphate (ATP) and
extracellular matrix (ECM) is increased. Formation of the glial scar is a complex
process that is primarily attributed to astrocytic proliferation, and the
fibrotic scar results from ECM deposition. In our previous researches, ATP and
fibronectin was able to separately stimulate the proliferation of astrocytes.
Moreover, fibronectin increases the expression of P2Y1 receptor and offers more
binding sites for ATP, which aggravates the proliferation. Meanwhile, ATP was
also able to stimulate the release of interleukin (IL)-6 and tumor necrosis
factor-alpha (TNF-alpha), but fibronectin does not. Recently, it has been
reported that over-expressing P2Y1 receptor could promote the level of Sox9.
However, the regulation of Sox genes by ATP is still little known in spinal cord
astrocytes. In the present study, we discovered that ATP was able to increase the
expression of Sox2 and Sox9; fibronectin did not have this direct function. Sox9
was only involved in the proliferation increased by ATP, and Sox2 influenced the
release of IL-6 stimulated by ATP. Understanding the critical role of Sox2 and
Sox9 mediated by ATP may provide a potential target for therapeutic intervention
in spinal cord injury.
PMID- 25115709
TI - Similarly up-regulated microRNA-106a in matched formalin-fixed paraffin-embedded
and fresh frozen samples and the dynamic changes during gastric carcinogenesis
and development.
AB - Evidence increasingly suggests that miR-106a is always elevated in gastric
cancer; however, little is known about the expression trend and clinical
significance in the whole process of gastric carcinogenesis and development. To
investigate the dynamic changes of miR-106a in each stage during gastric
carcinogenesis, we used formalin-fixed, paraffin-embedded (FFPE) tissues which
had been reported to have valuable information for miRNA research in our previous
studies. Here, we compared the expression of miR-106a in FFPE and fresh frozen
tissues using real-time polymerase chain reaction. On the basis of the high
correlation of miR-106a quantitative data from the two resources, FFPE samples
were subsequently performed to elucidate the location and expression of miR-106a
using in situ hybridization in sequential tissues, including normal gastric
mucosa, chronic atrophic gastritis combined with various degrees of dysplasia,
early and advanced gastric cancer. Finally, we found that miR-106a was similarly
up-regulated in gastric cancer regardless of sample types although fragmentation
existed inevitably in FFPE tissues. Notably, the frequency and extent of miR-106a
expression gradually increased during the transition from atypical hyperplasia to
advanced carcinoma and had already had positive signals in early precancerous
lesions but negative signals in normal gastric mucosal epithelial cells. Our
research, according to these results, indicated that FFPE samples can serve as an
important research tool for miRNA field, and the early changes of miR-106a
detected in such samples may have clinical application as a potential biomarker
for the discovery and diagnosis of gastric cancer.
PMID- 25115710
TI - Hourly differences in air pollution and risk of respiratory disease in the
elderly: a time-stratified case-crossover study.
AB - BACKGROUND: Epidemiological studies have shown adverse effects of short-term
exposure to air pollution on respiratory disease outcomes; however, few studies
examined this association on an hourly time scale. We evaluated the associations
between hourly changes in air pollution and the risk of respiratory disease in
the elderly, using the time of the emergency call as the disease onset for each
case. METHODS: We used a time-stratified case-crossover design. Study
participants were 6,925 residents of the city of Okayama, Japan, aged 65 or above
who were taken to hospital emergency rooms between January 2006 and December 2010
for onset of respiratory disease. We calculated city-representative hourly
average concentrations of air pollutants from several monitoring stations. By
using conditional logistic regression models, we estimated odds ratios per
interquartile-range increase in each pollutant by exposure period prior to
emergency call, adjusting for hourly ambient temperature, hourly relative
humidity, and weekly numbers of reported influenza cases aged >=60. RESULTS:
Suspended particulate matter (SPM) exposure 24 to <72 hours prior to the onset
and ozone exposure 48 to <96 hours prior to the onset were associated with the
increased risk of respiratory disease. For example, following one interquartile
range increase, odds ratios were 1.05 (95% confidence interval: 1.01, 1.09) for
SPM exposure 24 to <48 hours prior to the onset and 1.13 (95% confidence
interval: 1.04, 1.23) for ozone exposure 72 to <96 hours prior to the onset.
Sulfur dioxide (SO2) exposure 0 to <24 hours prior to onset was associated with
the increased risk of pneumonia and influenza: odds ratio was 1.07 per one
interquartile-range increase (95% confidence interval: 1.00, 1.14). Elevated risk
for pneumonia and influenza of SO2 was observed at shorter lags (i.e., 8-18
hours) than the elevated risks for respiratory disease of SPM or ozone. Overall,
the effect estimates for chronic obstructive pulmonary disease and allied
conditions were equivocal. CONCLUSIONS: This study provides further evidence that
hourly changes in air pollution exposure increase the risks of respiratory
disease, and that SO2 may be related with more immediate onset of the disease
than other pollutants.
PMID- 25115712
TI - [Anticipated efficacy of HPV vaccination in prophylaxis against nongenital
cancers].
AB - BACKGROUND: There is a considerable number of studies on the efficacy HPV (human
papillomavirus) vaccination against different cancers but relevant information is
scattered in diverse journals. This paper is a review summarizing current
knowledge of the potential of HPV vaccination against all HPV related cancers.
AIM: HPV infection is probably the most frequent sexually transmitted disease. At
least 13 HPV genotypes are classified as carcinogenic or probably carcinogenic in
respect to cervical cancer. Almost 100% of cervical cancers are linked to HPV
infection. HPV 16 and HPV 18 are the most frequently involved genotypes and
account together for approximately 70% of cervical cancer in the world.
Persistent high risk HPV infection is responsible for a significant proportion of
vulvar, vaginal, anal and penile carcinomas. The virus has also been implicated
in oncogenesis of head and neck cancers, including oropharyngeal cancers. HPV
infection can play an important role in cancerogenesis of lung, esophagus,
breast, and colon and rectum. On the contrary, published results indicate that
HPV infection is not associated with prostate oncogenesis. Strong predominance of
HPV 16 has been reported for all HPV associated cancer sites. Generally, it is
estimated that approximately 5.2% of all cancers are associated with oncogenic
HPV infection. Currently, there are two vaccines on the market; quadrivalent
Silgard(r) (Gardasil(r)) and bivalent CervarixTM. Large trials for both vaccines
have shown efficacy against HPV related infection and disease. Efficacy has been
very high in HPV naive subjects to vaccine related types. While HPV vaccination
is currently approved for the prevention of cervical cancer, it also has the
potential in the prevention of all HPV associated malignancies. The Czech
republic belongs to countries that cover HPV vaccination of girls at the age of
13- 14 years by general health insurance. Overall impact of this vaccination
remains to be evaluated. The new issues of the role of HPV in oncogenesis, as
well as the potential effect of HPV vaccination against HPV related nongenital
cancers are discussed. CONCLUSION: Approximately 5.2% of all human cancers are
associated with oncogenic human papillomavirus infection. HPV vaccination against
the most risky HPV oncotypes may cause a significant reduction of these cancers
mainly in the HPV naive population.
PMID- 25115713
TI - [Brazilian story of the R337H p53 mutation].
AB - The p53 tumor suppressor is an evergreen of molecular oncology. Since its
discovery in 1979, it has been subjected to intensive investigation. The p53
protein is composed of "only" 393 amino acid residues, and function of almost
each of them has been addressed in detail. Somatic mutations are extremely
frequent, they can be found almost in each of the p53 codons and in all types of
tumors. Inherited p53 mutations are rare but very penetrant, and they are
typically associated with development of a broad spectrum of tumors. However, in
2001, the p53 research provided an unexpected discovery: the R337H allele was
found in southern Brazil. This allele was atypically associated with only one
type of tumor - childhood adrenocortical carcinoma and it exhibited low
penetrance. Therefore, new data on functioning and impact of the R337H mutation
were highly desired. The results obtained during a few following years helped to
elucidate not only this specific p53 variant but also provided insight into
general principles of mutant p53 variants function. It also turned out that all
R337H alleles that are very frequent in southern Brazil originate from one common
ancestor.
PMID- 25115711
TI - Mobile elements and chromosomal changes associated with MLS resistance phenotypes
of invasive pneumococci recovered in the United States.
AB - Pneumococcal macrolide resistance is usually expressed as one of two phenotypes:
the M phenotype conferred by the mef gene or the MLSB phenotype caused by
modification of ribosomal targets, most commonly mediated by an erm methylase.
Target-site modification leading to antibiotic resistance can also occur due to
sequence mutations within the 23S rRNA or the L4 and L22 riboproteins. We
screened 4,535 invasive isolates resistant to erythromycin and 18 invasive
isolates nonsusceptible to quinupristin-dalfopristin (Q-D) to deduce the
potential mechanisms involved. Of 4,535 erythromycin-resistant isolates, 66.2%
were polymerase chain reaction (PCR)-positive for mef alone, 17.8% for ermB
alone, and 15.1% for both mef and ermB. Thirty-seven isolates (0.9%) were PCR
negative for both determinants. Of these, 3 were positive for ermA (subclass
ermTR) and 25 had chromosomal mutations. No chromosomal mutations (in 23S rRNA,
rplD, or rplV) nor any of the macrolides/lincosamides/streptogramin (MLS)
resistance genes screened for (ermT, ermA, cfr, lsaC, and vgaA) were found in the
remaining nine isolates. Of 18 Q-D nonsusceptible isolates, 14 had chromosomal
mutations and one carried both mef and ermB; no chromosomal mutations or other
resistance genes were found in 3 isolates. Overall, we found 28 mutations, 13 of
which have not been previously described in Streptococcus pneumoniae. The role of
these mutations remains to be confirmed by transformation assays.
PMID- 25115714
TI - [The cost study of first- line treatment of metastatic colorectal carcinoma with
bevacizumab- containing regimen in the Czech Republic].
AB - BACKGROUND: Bevacizumab, a humanized monoclonal IgG antibody against the vascular
endothelial growth factor (VEGF), is reimbursed in combination with chemotherapy
for the first and subsequent line treatment of patients with metastatic
colorectal cancer (mCRC) in the Czech Republic. However, its high cost is a
potentially limiting factor. We assessed the cost of bevacizumab in the treatment
of mCRC in a comprehensive cancer center. PATIENTS AND METHODS: A total of 218
patients were included in our analysis. Cost data (examination, medication,
hospitalization) were collected since the initiation of bevacizumab treatment to
any tumor response (RECIST criteria: complete response - CR, partial response -
PR, stable disease - SD, progressive disease - PD) and/ or to death. Minimal
followup for all patients was 28 months. Costs were valued in Czech crowns (CZK)
and converted to EUR (1? = 25.14 CZK). RESULTS: PD was recorded in 194 patients
(89% of patients). The mean cost of treatment to PD (median TTP 9.1 months) was
1,002,076.30 CZK (39,859.84 EUR). The majority of costs to PD was made by
medication - 917,048.60 CZK (36,477.67 EUR) per patient. The mean cost to
response PR, CR or SD was 1,105,823.10 CZK (43,986.60 EUR) after median 9.8
months of treatment (recorded for 21 patients), medication formed 1,023,827.70
CZK (40,725.05 EUR). During the study, 170 patients (78%) died. The mean of the
total costs since initiation of treatment to death (median OS 18.8 months) was
1,338,874.20 CZK (53,256.70 EUR) - out of that, medication was 1,184,251.10 CZK
(47,106.25 EUR) per patient. CONCLUSION: Targeted bio-logical therapy is the
largest part of the costs of mCRC therapy. Cost of bevacizumab made up to 69% of
costs to PD - 687,608.20 CZK ( 27,351.20 EUR ) per patient. The majority of the
total cost was formed by targeted drug therapy (bevacizumab in 1st line therapy,
cetuximab and panitumumab in 2nd and 3rd line therapy); 58% of total costs since
initiation of treatment to death - 778,233.80 CZK (30,956 EUR) per patient.
PMID- 25115715
TI - [Screening of malnutrition risk versus indicators of nutritional status and
systemic inflammatory response in newly diagnosed lung cancer patients].
AB - BACKGROUND: Most lung cancers are already advanced at the time of dia-gnosis. In
these patients, a frequent symptom is protein energy malnutrition, often
diagnosed prior to oncological treatment. Malnutrition results in poor tolerance
of treatment and increased morbidity and mortality. METHODS: Nutritional Risk
Screening (NRS) 2002 adapted for oncological patients was used to assess the risk
of undernutrition in a group of 188 lung cancer patients. The risk was evaluated
on a 6- point scale according to common signs of nutritional status and tumor and
its treatment risk factors. A score of 3 and more (called "nutritional risk")
means a significant risk of malnutrition. Furthermore, pretreatment nutritional
characteristics were evaluated in patients (including the value of BMI) and
laboratory values indicating malnutrition/ acute phase response (albumin/ C
reactive protein - CRP). RESULTS: Acceptable NRS score was found in 50.6%, while
in 45.3% was suggested into risk of malnutrition ("nutritional risk"). Only 6.6%
of our patients had a BMI less than 20 kg/ m2. Significant differences in albumin
and CRP values in various categories of NRS were confirmed. CONCLUSION: Initial
signs of cancer malnutrition may be overlooked in patients who fall within or
above the range of BMI for adequate weight, although these patients may be at
significant risk of malnutrition. The indicators of nutritional status and
systemic inflammatory responses were significantly associated with resulting
values NRS score.
PMID- 25115716
TI - [Relation between carbonic anhydrase IX serum level, hypoxia and radiation
resistance of head and neck cancers].
AB - BACKGROUND: Hypoxia of locally advanced head and neck cancers is one of the main
causes of their radiation resistance that presents clinically as a persistence of
residual tumor disease after radiation therapy. Therefore, detection of tumor
hypoxia could be an important predictor of treatment efficacy. Carbonic anhydrase
IX (CA IX) is a protein, coded by a homonymous gene, the expression of which
increases in tumor tissues at hypoxic conditions. Hence, CA IX represents an
endogenic marker of tumor hypoxia, identifiable in tumor tissues, and its soluble
extracellular domain can also be detected in body fluids of the patient. The
primary endpoint of this study was to explore whether a correlation exists
between CA IX serum level and the residual tumor disease after therapy. The
secondary endpoint was to find out how the serum concentration of CA IX changes
during the course of fractionated radiation therapy. MATERIALS AND METHODS: The
presented prospective monocentric clinical study evaluated a population of 30
patients with locally advanced squamous cell head and neck cancers, treated by
radiation therapy or concurrent chemo radiation therapy with a curative intent.
The serum concentration of the soluble form of CA IX was examined from a venous
blood sample, using sandwich enzyme linked immunosorbent assay (ELISA). The blood
samples were obtained before the treatment initiation, in the middle of radiation
therapy, at the time of finishing radiation therapy and six weeks after the
treatment completion. RESULTS: We found a substantial variability in the CA IX
levels measured in the examined population, ranging 0- 1,696 pg/ ml. We found no
significant changes in the mean value of CA IX concentration during the course of
radiation therapy and after the treatment completion. In 11 patients (36.7%), the
treatment resulted in complete remission of the disease. In these patients, lower
average pretreatment levels of CA IX were noted when compared to patients with
persistence of residual tumor disease (37.57 vs 77.47; p = 0.154). CONCLUSION:
The results indicate that serum level of CA IX in patients with locally advanced
head and neck cancers does not change significantly during the course of
fractionated radiation therapy. The relation between CA IX serum level and
residual tumor disease after radiation therapy requires verification on a larger
population of patients.
PMID- 25115717
TI - Impact of anakinra treatment on cytokine and lymphocytes/ monocytes profile of an
Erdheim-Chester patient.
AB - BACKGROUND: Erdheim-Chester disease (ECD) is a rare non-Langerhans cells
histiocytosis associated with intense immune activation. In our clinical center,
an ECD patient was treated with anakinra, IL1RA (interleukin1 receptor
antagonist), resulting in clinical improvement and major decrease of pathological
fatigue. The aim of the study was to evaluate changes in cytokine profile and
shift of immune cells estimated by flow cytometric analysis of ECD patient
before, during initial stages of anakinra treatment as well as after treatment
ceased in comparison to healthy donors. METHODS: Singleplex reactions of 19
individual cytokines from serum of ECD patient were measured by FACS array. Flow
cytometric analyses were performed on peripheral blood cells. RESULTS: The most
striking result is substantial decrease of IL6 immediately after anakinra
treatment started suggesting a major role of IL1 pathway in ECD pathophysiology.
As for flow cytometric analysis, increased number of CD16+ monocytes before
treatment is a new finding. CONCLUSION: Our results suggest that IL6 may be a
marker of early treatment response of ECD patients treated with anakinra.
PMID- 25115718
TI - Positron emission tomography combined with computed tomography for diagnosis of
synchronous tumors.
AB - BACKGROUND: The hybrid method 18F-FDG PET/ CT has been proven as a method of
choice in oncology for diagnostics, staging, restaging of the tumor and
evaluation of the therapeutic effect. The aim of the study was to determine the
value of 18F-FDG PET/ CT for detection of synchronous tumors and consequently the
influence on the patients management. MATERIAL AND METHODS: The examinations were
performed on Discovery, GE Healthcare PET/ CT using standard protocol. Among the
patients, examined by 18F FDG PET/ CT for one year (n = 1 408), unsuspected
synchronous tumors were detected in 11 cases (0.8%). RESULTS: Five pulmonary
carcinomas, four head and neck squamous cell carcinomas (HNSCC), one ovarian
carcinoma and one tumor of the sigma were detected as second malignancies. The
histology verification was done in five cases (all HNSCC and one sigma
carcinoma). In one patient with ovarian carcinoma, histology was obtained after
surgery. In the rest of patients, no verification was undertaken because of the
patients refusal and the advanced stage of the diseases, demanding systemic
chemotherapy. Four patients (three with HNSCC and one with ovarian secondary
malignancy) had favorable outcome during the nine month follow up. CONCLUSION:
The hybrid method PET/ CT, combining the metabolic and morphologic findings, can
help detection of synchronous malignancies in a small percentage of cases, but
with a positive influence on management of considerable part of such patients.
PMID- 25115719
TI - [Paraneoplastic vasculitis in a patient with cervical cancer].
AB - BACKGROUND: Paraneoplastic syndromes precede the dia-gnosis of malignancy. Early
detection of paraneoplastic syndrome may lead to detection of malignancy in its
early and potentially curable stage. Differential diagnostic process of rare
paraneoplastic vasculitis requires multidisciplinary cooperation between
rheumatologists, radiologists and oncologists. CASE: 41 year old female patient
with cervical cancer in stage IVB (paraaortic lymphadenopathy) and clinical
symptoms of acute vasculitis was admitted to our ward for oncological treatment.
Chemoradiotheraphy was initiated concurrently with corticotherapy. During the
treatment we observed alleviation of vasculitis related symptoms. Ongoing
followup, however, brought no further improvement in vasculitis related symptoms.
This lead us to suspicion of recurrence, confirmed on CT scan. Palliative
chemotherapy was without any effect and due to worsening performance status was
terminated. CONCLUSION: The activity of vasculitis was closely associated with
the activity of primary malignant disease. Early recognition of paraneoplastic
syndrome may contribute not only to dia-gnosis of malignancy, but is helpful
during followup of these patients.
PMID- 25115720
TI - [Acupuncture in the treatment of symptoms of oncological diseases in the Western
world].
AB - Acupuncture is one of the methods of traditional Chinese Medicine (TCM). In Asia,
methods of TCM are quite often used in oncological patients in combination with
classical medicine. In Europe and North America, the position of the TCM is not
so clear. In the last few years, some studies were done which were supposed to
verify scientifically the effectiveness of acupuncture in the treatment of some
symptoms in oncological patients and adverse effects of oncological treatment.
Results of these studies indicate that acupuncture is effective in the treatment
of pain, nausea, vomiting and xerostomia. The International Society of
Integrative Oncology formulated some recommendations for using methods of TCM in
oncological patients. In this field, there is still a lot of possibilities for
further studies which could help acupuncture to become an important therapeutic
method even in our region.
PMID- 25115721
TI - Dendritic cell vaccines against non-small cell lung cancer - an emerging
therapeutic alternative.
AB - Many clinical trials have been carried out or are in progress to assess the
therapeutic potential of dendritic cell-based vaccines on cancer patients.
Herewith, we describe the clinical trials of nonsmall cell lung cancer (NSCLC)
published in the literature. Although the number of clinical trials and NSCLC
patients enrolled in these studies is small, it is possible to conclude that the
administration of dendritic cells (DCs) by any route is safe and that a clinical
benefit after their administration can be observed. These initial results
encourage continued investigation in clinical trials into the benefit of DCs
along with different strategies to enhance their immune response in this deadly
disease.
PMID- 25115725
TI - The use of the cluster randomized crossover design in clinical trials: protocol
for a systematic review.
AB - BACKGROUND: The cluster randomized crossover (CRXO) design is gaining popularity
in trial settings where individual randomization or parallel group cluster
randomization is not feasible or practical. In a CRXO trial, not only are
clusters of individuals rather than individuals themselves randomized to trial
arms, but also each cluster participates in each arm of the trial at least once
in separate periods of time.We will review publications of clinical trials
undertaken in humans that have used the CRXO design. The aim of this systematic
review is to summarize, as reported: the motivations for using the CRXO design,
the values of the CRXO design parameters, the justification and methodology for
the sample size calculations and analyses, and the quality of reporting the CRXO
design aspects. METHODS/DESIGN: We will identify reports of CRXO trials by
systematically searching MEDLINE, PubMed, Cochrane Methodology Register, EMBASE,
and CINAHL Plus. In addition, we will search for methodological articles that
describe the CRXO design and conduct citation searches to identify any further
CRXO trials. The references of all eligible trials will also be searched. We will
screen the identified abstracts, and retrieve and assess for inclusion the full
text for any potentially relevant articles. Data will be extracted from the full
text independently by two reviewers. Descriptive summary statistics will be
presented for the extracted data. DISCUSSION: This systematic review will inform
both researchers addressing CRXO methodology and trialists considering
implementing the design. The results will allow focused methodological research
of the CRXO design, provide practical examples for researchers of how CRXO trials
have been conducted, including any shortcomings, and highlight areas where
reporting and conduct may be improved.
PMID- 25115726
TI - A new microscopic insight into membrane penetration and reorganization by PETIM
dendrimers.
AB - Dendrimers are highly branched polymeric nanoparticles whose structure and
topology, largely, have determined their efficacy in a wide range of studies
performed so far. An area of immense interest is their potential as drug and gene
delivery vectors. Realizing this potential, depending on the nature of cell
surface-dendrimer interactions, here we report controlled model membrane
penetration and reorganization, using a model supported lipid bilayer and
poly(ether imine) (PETIM) dendrimers of two generations. By systematically
varying the areal density of the lipid bilayers, we provide a microscopic
insight, through a combination of high resolution scattering, atomic force
microscopy and atomistic molecular dynamics simulations, into the mechanism of
PETIM dendrimer membrane penetration, pore formation and membrane re-organization
induced by such interactions. Our work represents the first systematic
observation of a regular barrel-like membrane spanning pore formation by
dendrimers, tunable through lipid bilayer packing, without membrane disruption.
PMID- 25115728
TI - Volatile constituents of Dianthus rupicola Biv. from Sicily: activity against
microorganisms affecting cellulosic objects.
AB - Dianthus rupicola Biv. (cliffs carnation) is a camephytic, suffruticous,
perennial plant growing up to 40 cm high. The plant is widespread in Sicily and
neighbouring islands (Egadi, Lampedusa, Lipari) and in some areas of southern
Italy. GC and GC-MS analyses of the essential oil distilled from the flowers
showed the presence of 66 components. Its composition is characterised by the
high content of thymol and carvacrol derivatives. A good antibacterial activity
against Bacillus cereus and Bacillussubtilis, both infesting cellulosic
historical material, was shown, whereas the antioxidant capacity was determined
to be quite poor.
PMID- 25115727
TI - Lithium ameliorates lipopolysaccharide-induced microglial activation via
inhibition of toll-like receptor 4 expression by activating the PI3K/Akt/FoxO1
pathway.
AB - BACKGROUND: Lithium, an effective mood stabilizer for the treatment of bipolar
disorders, has been recently suggested to have a role in neuroprotection during
neurodegenerative diseases. The pathogenesis of neurological disorders often
involves the activation of microglia and associated inflammatory processes. Thus,
in this study, we aimed to understand the role of lithium in microglial
activation and to elucidate the underlying mechanism(s). METHODS: Primary
microglial cells were pretreated with lithium and stimulated with
lipopolysaccharide (LPS). The cells were assessed regarding the responses of pro
inflammatory cytokines, and the associated signaling pathways were evaluated.
RESULTS: Lithium significantly inhibited LPS-induced microglial activation and
pro-inflammatory cytokine production. Further analysis showed that lithium could
activate PI3K/Akt signaling. Analyses of the associated signaling pathways
demonstrated that the lithium pretreatment led to the suppression of LPS-induced
toll-like receptor 4 (TLR4) expressions via the PI3K/Akt/FoxO1 pathway.
CONCLUSIONS: This study demonstrates that lithium can inhibit LPS-induced TLR4
expression and microglial activation through the PI3K/Akt/FoxO1 signaling
pathway. These results suggest that lithium plays an important role in microglial
activation and neuroinflammation-related diseases, which may lead to a new
therapeutic strategy for the treatment of neuroinflammation-related disorders.
PMID- 25115729
TI - Reducing readmissions following paediatric cardiothoracic surgery: a quality
improvement initiative.
AB - BACKGROUND: We have previously identified risk factors for readmission following
congenital heart surgery - Hispanic ethnicity, failure to thrive, and original
hospital stay more than 10 days. As part of a quality initiative, changes were
made to the discharge process in hopes of reducing the impact. All discharges
were carried out with an interpreter, medications were delivered to the hospital
before discharge, and phone calls were made to families within 72 hours following
discharge. We hypothesised that these changes would decrease readmissions.
METHODS: The current cohort of 635 patients underwent surgery in 2012.
Demographic, preoperative, operative, and postoperative variables were evaluated.
Univariate and multivariate risk factor analyses were performed. Comparisons were
made between the initial (2009) and the current (2012) cohorts. RESULTS: There
were 86 readmissions of 77 patients during 2012. Multivariate risk factors for
readmission were risk adjustment for congenital heart surgery score and initial
hospital stay >10 days. In comparing 2009 with 2012, the overall readmission rate
was similar (10 versus 12%, p=0.27). Although there were slight decreases in the
2012 readmissions for those patients with Hispanic ethnicity (18 versus 16%,
p=0.79), failure to thrive (23 versus 17%, p=0.49), and initial hospital stay >10
days (22 versus 20%, p=0.63), they were not statistically significant.
CONCLUSIONS: Potential risk factors for readmission following paediatric
cardiothoracic surgery have been identified. Although targeted modifications in
discharge processes can be made, they may not reduce readmissions. Efforts should
continue to identify modifiable factors that can reduce the negative impact of
hospital readmissions.
PMID- 25115730
TI - How do recent classifications give a new insight for the management of
emphysematous pyelonephritis?
PMID- 25115731
TI - Extracellular molecular effectors mediating probiotic attributes.
AB - Interest in probiotic bacteria, in the context of health and disease, is
increasing and gathering scientific evidence, as is reflected by their growing
utilization in food and pharma industry. As a consequence, many research effort
over the past few years has been dedicated to discern the molecular mechanisms
responsible for their purported attributes. Remarkably, whereas the traditional
probiotic concept assumes that bacteria must be alive during their administration
to exert health-promoting effects, evidence is being accumulated that supports
defined bacterial secreted molecules and/or isolated surface components mediating
attributed cross talk dialogue between the host and the probiotic cells. Indeed,
administration of the isolated bacterial-derived metabolites or molecules may be
sufficient to promote the desired effects and may represent a promising safer
alternative in inflammatory disorders. Here, we summarize the current knowledge
of molecular effectors of probiotic bacteria that have been involved in mediating
their effects.
PMID- 25115732
TI - Comparative study of the metal accumulation in Hysterothalycium reliquens
(nematode) and Paraphilometroides nemipteri (nematode) as compared with their
doubly infected host, Nemipterus peronii (Notched threadfin bream).
AB - In February 2013, forty-seven Notched threadfin bream, the Nemipterus peronii,
were sampled from the eastern coastal waters of the South China Sea. The
concentration of various elements, namely cadmium (Cd), chromium (Cr), copper
(Cu), mercury (Hg), strontium (Sr), manganese (Mn), selenium (Se), Lead (Pb),
nickel (Ni), aluminum (Al), arsenic (As), iron (Fe), and Zinc (Zn) were analyzed
in the liver, muscle, and kidney organs of the host, as well as in their
parasites Hysterothalycium reliquens (nematode) and the Paraphilometroides
nemipteri (nematode), using inductively coupled plasma mass spectrometry (ICP
MS). The former group of parasites showed highest accumulation capacity for Cr,
Cu, Fe, Mn, Se, Ni, and Zn while the latter group had high accumulation potential
of As, Hg, Cd, Al, Pb, and Sr. The divergence in heavy-metal accumulation
profiles of both nematodes is linked with the specificity of microhabitats,
cuticle morphology, and interspecific competition. The outcome of this study
indicates that both parasite models can be used for biomonitoring of metal
pollution in marine ecosystems.
PMID- 25115735
TI - Anode catalysts for direct hydrazine fuel cells: from laboratory test to an
electric vehicle.
AB - Novel highly active electrocatalysts for hydrazine hydrate fuel cell application
were developed, synthesized and integrated into an operation vehicle prototype.
The materials show in both rotating disc electrode (RDE) and membrane electrode
assembly (MEA) tests the world highest activity with peak current density of
16,000 A g(-1) (RDE) and 450 mW cm(-2) operated in air (MEA).
PMID- 25115734
TI - Vasorelaxation induced by methyl cinnamate, the major constituent of the
essential oil of Ocimum micranthum, in rat isolated aorta.
AB - The aim of the present study was to investigate the vascular effects of the E
isomer of methyl cinnamate (E-MC) in rat isolated aortic rings and the putative
mechanisms underlying these effects. At 1-3000 MUmol/L, E-MC concentration
dependently relaxed endothelium-intact aortic preparations that had been
precontracted with phenylephrine (PHE; 1 MUmol/L), with an IC50 value (geometric
mean) of 877.6 MUmol/L (95% confidence interval (CI) 784.1-982.2 MUmol/L). These
vasorelaxant effects of E-MC remained unchanged after removal of the vascular
endothelium (IC50 725.5 MUmol/L; 95% CI 546.4-963.6 MUmol/L) and pretreatment
with 100 MUmol/L N(G) -nitro-l-arginine methyl ester (IC50 749.0 MUmol/L; 95% CI
557.8-1005.7 MUmol/L) or 10 MUmol/L 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one
(IC50 837.2 MUmol/L; 95% CI 511.4-1370.5 MUmol/L). Over the concentration range 1
3000 MUmol/L, E-MC relaxed K(+) -induced contractions in mesenteric artery
preparations (IC50 314.5 MUmol/L; 95% CI 141.9-697.0 MUmol/L) with greater
potency than in aortic preparations (IC50 1144.7 MUmol/L; 95% CI 823.2-1591.9
MUmol/L). In the presence of a saturating contractile concentration of K(+) (150
mmol/L) in Ca(2+) -containing medium combined with 3 MUmol/L PHE, 1000 MUmol/L E
MC only partially reversed the contractile response. In contrast, under similar
conditions, E-MC nearly fully relaxed PHE-induced contractions in aortic rings in
a Ba(2+) -containing medium. In preparations that were maintained under Ca(2+)
free conditions, 600 and 1000 MUmol/L E-MC significantly reduced the contractions
induced by exogenous Ca(2+) or Ba(2+) in KCl-precontracted preparations, but not
in PHE-precontracted preparations (in the presence of 1 MUmol/L verapamil). In
addition, E-MC (1-3000 MUmol/L) concentration-dependently relaxed the
contractions induced by 2 mmol/L sodium orthovanadate. Based on these
observations, E-MC-induced endothelium-independent vasorelaxant effects appear to
be preferentially mediated by inhibition of plasmalemmal Ca(2+) influx through
voltage-dependent Ca(2+) channels. However, the involvement of a myogenic
mechanism in the effects of E-MC is also possible.
PMID- 25115736
TI - Polymer-free patterning of graphene at sub-10-nm scale by low-energy repetitive
electron beam.
AB - A polymer-free technique for generating nanopatterns on both synthesized and
exfoliated graphene sheets is proposed and demonstrated. A low-energy (5-30 keV)
scanning electron beam with variable repetition rates is used to etch suspended
and unsuspended graphene sheets on designed locations. The patterning mechanisms
involve a defect-induced knockout process in the initial etching stage and a heat
induced curling process in a later stage. Rough pattern edges appear due to
inevitable stochastic knockout of carbon atoms or graphene structure imperfection
and can be smoothed by thermal annealing. By using this technique, the minimum
feature sizes achieved are about 5 nm for suspended and 7 nm for unsuspended
graphene. This study demonstrates a polymer-free direct nanopatterning approach
for graphene.
PMID- 25115733
TI - The major bioactive components of seaweeds and their mosquitocidal potential.
AB - Seaweeds are one of the most widely studied natural resources for their
biological activities. Novel seaweed compounds with unique chemical structures
have been reported for their pharmacological properties. The urge to search for
novel insecticidal compound with a new mode of action for development of
botanical insecticides supports the relevant scientific research on discovering
the bioactive compounds in seaweeds. The mosquitocidal potential of seaweed
extracts and their isolated compounds are documented in this review paper, along
with the discussion on bioactivities of the major components of seaweeds such as
polysaccharides, phenolics, proteins, terpenes, lipids, and halogenated
compounds. The effects of seaweed extracts and compounds toward different life
stages of mosquito (egg, larva, pupa, and adult), its growth, development, and
reproduction are elaborated. The structure-activity relationships of
mosquitocidal compounds are discussed to extrapolate the possible chemical
characteristics of seaweed compounds responsible for insecticidal properties.
Furthermore, the possible target sites and mode of actions of the mosquitocidal
seaweed compounds are included in this paper. The potential synergistic effects
between seaweeds and commercial insecticides as well as the toxic effects of
seaweed extracts and compounds toward other insects and non-target organisms in
the same habitat are also described. On top of that, various factors that
influence the mosquitocidal potential of seaweeds, such as abiotic and biotic
variables, sample preparation, test procedures, and considerations for a precise
experimental design are discussed. The potential of active seaweed extracts and
compounds in the development of effective bioinsecticide are also discussed.
PMID- 25115737
TI - Clinical outcomes of children and adults with central nervous system primitive
neuroectodermal tumor.
AB - Central nervous system primitive neuroectodermal tumors (CNS PNETs) predominantly
occur in children and rarely in adults. Because of the rarity of this tumor, its
outcomes and prognostic variables are not well characterized. The purpose of this
study was to evaluate clinical outcomes and prognostic factors for children and
adults with CNS PNET. The records of 26 patients (11 children and 15 adults) with
CNS PNET from 1991 to 2011 were reviewed retrospectively. Disease-free survival
(DFS) and overall survival (OS) were estimated with the Kaplan-Meier method, and
relevant prognostic factors were analyzed. For the cohort, both the 5-year DFS
and the OS were 46 %. For pediatric patients, the 5-year DFS was 78 %; for adult
patients, it was 22 % (P = 0.004). Five-year OS for the pediatric and adult
patients was 67 and 33 %, respectively (P = 0.07). With bivariate analysis
including chemotherapy regimen (high dose vs. standard vs. nonstandard) or risk
stratification (standard vs. high) and age, the increased risk of disease
recurrence in adults persisted. A nonsignificant tendency toward poorer OS in
adult patients relative to pediatric patients also persisted. High-dose
chemotherapy with stem cell rescue was associated with a statistically
significant improvement in OS and a tendency toward improved DFS, although the
findings were mitigated when the effect of age was considered. Local recurrence
was the primary pattern of treatment failure in both adults and children. Our
results suggest that adult patients with CNS PNETs have inferior outcomes
relative to the pediatric cohort. Further research is needed to improve outcomes
for CNS PNET in populations of all ages.
PMID- 25115739
TI - Impact of health-related quality of life and fatigue on survival of recurrent
high-grade glioma patients.
AB - Quality of life (QoL) impairment and fatigue are frequently experienced during
treatment for recurrent high-grade glioma (HGG). Fatigue and QoL impairments can
be due to primary neurological dysfunction, cytotoxic treatments, mood
disturbances, and supportive medications. We now seek to understand how QoL and
fatigue impacts survival in recurrent HGG. Using a prospective observational
design, 237 patients with recurrent HGG and KPS >=70 completed a self
administered questionnaire that evaluated QoL and fatigue. QoL was assessed with
Functional Assessment of Cancer Therapy-General (FACT-G) and FACT-Brain (FACT-Br)
scales while fatigue was assessed using Functional Assessment of Chronic Illness
Therapy (FACIT-F) scale. Cox proportional hazard models were utilized to evaluate
the association between QoL and fatigue and survival. Seventy-three (31 %)
subjects had recurrent WHO grade III gliomas and 164 (69 %) had recurrent WHO
grade IV gliomas. Median follow-up analysis was 27.60 months. In univariate Cox
analyses, the FACT-Br specific subscale (HR 0.88; CI 95 %, 0.77-1; p = 0.048) and
FACIT-F (HR 0.82; CI 95 %, 0.68-0.99; p = 0.045) were both significant predictors
of survival. Fatigue added prognostic information beyond that provided by KPS,
age, sex, tumor grade, and number of prior progressions (HR 0.80; CI 95 %, 0.68
0.9; p = 0.031). A greater degree of fatigue was associated with poorer survival
in recurrent HGG patients. In multivariable analyses, FACT-G and FACT-Br are not
independent predictors of prognosis. Fatigue is a strong independent predictor of
survival that provides incremental prognostic value to the traditional markers of
prognosis in recurrent HGG. Pharmacological or non-pharmacological strategies to
treat fatigue warrant investigation.
PMID- 25115738
TI - Therapeutic implications of CD1d expression and tumor-infiltrating macrophages in
pediatric medulloblastomas.
AB - Immunobiology of medulloblastoma (MB), the most common malignant brain tumor in
children, is poorly understood. Although tumor cells in some MBs were recently
shown to express CD1d and be susceptible to Valpha24-invariant natural killer T
(NKT)-cell cytotoxicity, the clinical relevance of CD1d expression in MB patients
remains unknown. We investigated the expression of CD1d in pediatric MBs and
correlated with molecular and clinical characteristics. Specifically, we explored
if NKT cell therapy can be targeted at a subset of pediatric MBs with poorer
prognosis. Particularly, infantile MBs have a worse outcome because radiotherapy
is delayed to avoid neurocognitive sequelae. Immunohistochemistry for CD1d was
performed on a screening set of 38 primary pediatric MBs. Gene expression of the
membrane form of M2 macrophage marker, CD163, was studied in an expanded cohort
of 60 tumors. Outcome data was collected prospectively. Thirteen of 38 MBs (34.2
%) expressed CD1d on immunohistochemistry. CD1d was expressed mainly on MB tumor
cells, and on some tumor-associated macrophages. Majority (18/22, 82 %) of non
sonic-hedgehog/Wingless-activated MBs (group 3 and 4) were CD1d-negative (p =
0.05). A subset of infantile MBs (4/9, 44.4 %) expressed CD1d. Macrophages
infiltrating MB expressed CD163 apart from CD1d. Molecular subtypes demonstrated
statistical differences in CD163 expression, SHH-tumors were the most enriched (p
= 0.006). Molecular and clinical subtypes of pediatric MB exhibit distinct
differences in CD1d expression, which have important therapeutic implications.
High CD1d expression in infantile MBs offers potential new immunotherapeutic
treatment with NKT cell therapy in infants, where treatment is suboptimal due
delayed radiotherapy.
PMID- 25115740
TI - Profiling Hsp90 differential expression and the molecular effects of the Hsp90
inhibitor IPI-504 in high-grade glioma models.
AB - Retaspimycin hydrochloride (IPI-504), an Hsp90 (heat shock protein 90) inhibitor,
has shown activity in multiple preclinical cancer models, such as lung, breast
and ovarian cancers. However, its biological effects in gliomas and normal brain
derived cellular populations remain unknown. In this study, we profiled the
expression pattern of Hsp90alpha/beta mRNA in stable glioma cell lines, multiple
glioma-derived primary cultures and human neural stem/progenitor cells. The
effects of IPI-504 on cell proliferation, apoptosis, motility and expression of
Hsp90 client proteins were evaluated in glioma cell lines. In vivo activity of
IPI-504 was investigated in subcutaneous glioma xenografts. Our results showed
Hsp90alpha and Hsp90beta expression levels to be patient-specific, higher in high
grade glioma-derived primary cells than in low-grade glioma-derived primary
cells, and strongly correlated with CD133 expression and differentiation status
of cells. Hsp90 inhibition by IPI-504 induced apoptosis, blocked migration and
invasion, and significantly decreased epidermal growth factor receptor levels,
mitogen-activated protein kinase and/or Akt activities, and secretion of vascular
endothelial growth factor in glioma cell lines. In vivo study showed that IPI-504
could mildly attenuate tumor growth in immunocompromised mice. These findings
suggest that targeting Hsp90 by IPI-504 has the potential to become an active
therapeutic strategy in gliomas in a selective group of patients, but further
research into combination therapies is still needed.
PMID- 25115741
TI - Early development of congeneric sea urchins (Heliocidaris) with contrasting life
history modes in a warming and high CO2 ocean.
AB - The impacts of ocean change stressors - warming and acidification - on marine
invertebrate development have emerged as a significant impact of global change.
We investigated the response of early development to the larval stage in
sympatric, congeneric sea urchins, Heliocidaris tuberculata and Heliocidaris
erythrogramma with contrasting modes of development to ocean warming and
acidification. Effects of these stressors were assessed by quantifying the
percentage of normal development during the first 24 h post fertilization, in
cross-factorial experiments that included three temperature treatments (control:
20 degrees C; +4: 24 degrees C; +6: 26 degrees C) and four pHNIST levels
(control: 8.2; -0.4: 7.8; -0.6: 7.6; -0.8: 0.4). The experimental treatments were
designed in context with present day and near-future (~2100) conditions for the
southeast Australia global warming hotspot. Temperature was the most important
factor affecting development of both species causing faster progression through
developmental stages as well as a decrease in the percentage of normal
development. H. erythrogramma embryos were less tolerant of increased temperature
than those of H. tuberculata. Acidification impaired development to the larval
stage in H. tuberculata, but this was not the case for H. erythrogramma. Thus,
outcomes for the planktonic life phase of the two Heliocidaris species in
response to ocean warming and acidification will differ. As shown for these
species, single-stressor temperature or acidification studies can be misleading
with respect to determining species' vulnerability and responses to global
change.
PMID- 25115742
TI - Editorial Comment from Dr Zampieri to Is the presence of varicocele associated
with static and dynamic components of benign prostatic hyperplasia/lower urinary
tract symptoms in elderly men?
PMID- 25115743
TI - Sex is a stronger predictor of colorectal adenoma and advanced adenoma than fecal
occult blood test.
AB - Due to high costs and limited availability of screening colonoscopy, some
screening programs require a positive fecal occult blood test (FOBT) before
screening colonoscopy is remunerated. As male sex is a strong predictor of
adenoma and advanced adenoma, we evaluated whether a positive FOBT or male sex is
a stronger risk factor for adenoma and advanced adenoma. FOBT and screening
colonoscopy results from 18.665 consecutive patients participating in a "national
health check program" between 2009 and 2011 were included in this cohort study.
Age-corrected adenoma detection rates (ADR), advanced adenoma detection rates
(AADR) and carcinoma detection rates were calculated for men and women according
to FOBT result separately. ADR and AADR in FOBT-positive men (34.6 and 11.8 %)
and FOBT-negative men (29.1 and 7.6 %) were higher than ADR and AADR in FOBT
positive women (20 and 6.9 %) and in FOBT-negative women (17.6 and 4.4 %), (p =
0.0003). Men with negative FOBT were at higher risk of having an adenoma and
advanced adenoma than women with positive FOBT (p < 0.0001). Odds ratios of a
positive FOBT for ADR and AADR were 1.3 (1.1-1.5) (p = 0.0047) and 1.6 (1.2-2.1)
(p < 0.0001), respectively. Odds ratios of male sex to predict ADR and AADR were
significantly higher with 1.9 (1.8-2.1) and 1.8 (1.6-2), respectively (p <
0.001). Male sex is a stronger predictor for colorectal adenoma and advanced
adenoma than positive FOBT. These results should be taken into account analyzing
FOBT-based screening programs.
PMID- 25115744
TI - Use of "Real-World" data to describe adverse events during the treatment of
metastatic renal cell carcinoma in routine clinical practice.
AB - Insights into the experience of metastatic renal cell carcinoma (mRCC) patients
are needed to optimize patient care. A retrospective, multicenter registry of
mRCC patients treated at academic (Duke) and community (ACORN) practices was
developed to fill this need. Treatment data were collected on 466 patients who
received first-line therapy from 2007 to 2011. Clinically significant adverse
events (AEs) were abstracted from medical records and compared to clinical
trials. Two hundred and seventy patients received first-line therapy with
sunitinib, 60 temsirolimus, 53 sorafenib, 25 pazopanib, and 58 "other." A total
of 85.8 % of all patients experienced at least one AE: fatigue (56.7 %), vomiting
(40.1 %), diarrhea (33.7 %), asthenia (32.8 %), and mucosal inflammation (20.8
%). When comparisons were made between patients >65 versus <65 years old, rates
of AEs were higher in the younger group. Dosing approaches and timing of AEs
during therapy were varied. These data shine light on the patient experience in
routine practice versus structured clinical trials. Real-world AE frequency and
severity differ from pivotal trials demonstrating the need to monitor patients
closely and manage their AEs to optimize outcomes. As the number of treatment
options with similar effectiveness grows, it is imperative to understand the real
world patient experience.
PMID- 25115746
TI - Physician's emerging roles relating to trends in health information technology.
AB - Objective: To determine the new roles that physicians will adopt in the near
future to adjust to accelerating trends from managed care to outcome-based
practice to health care reform to health information technology to the evolving
role of health consumers. Methods: Trends and related developments concerning the
changing roles of physicians based on prior literature reviews. Results: Six
possible roles, traditional, gatekeeper, coach, navigator, informatician and one
voice among many, are discussed in terms of physician's centrality, patient
autonomy, decision-making and uncertainty, information seeking, satisfaction and
outcomes, particularly those related to compliance. Conclusion: A greater
understanding of these emerging roles could lead to more efficacious outcomes in
our ever changing, increasingly complex medical system. Patients often have
little understanding of emerging trends that lead to the development of
specialized roles such as hospitalist and navigators and, relatedly, the evolving
roles of physicians.
PMID- 25115745
TI - Effect of MLH1 -93G>A on gene expression in patients with colorectal cancer.
AB - The DNA repair machinery plays a key role in maintaining genomic stability by
preventing the emergence of mutations. Furthermore, the -93G>A polymorphism in
the MLH1 gene has been associated with an increased risk of developing colorectal
cancer. Therefore, the aim of this study was to examine the expression pattern
and effect of this polymorphism in normal and tumour samples from patients with
colorectal cancer. The MLH1 -93G>A (rs1800734) polymorphism was detected by PCR
RFLP in 49 cases of colorectal cancer. MLH1 expression was investigated using
real-time quantitative PCR. The results indicate a significant decrease in MLH1
expression in tumour samples compared to their normal counterparts. The MLH1 gene
was also significantly repressed in samples from patients who had some degree of
tumour invasion into other organs. Similarly, those patients who were in a more
advanced tumour stage (TNM III and IV) exhibited a significant reduction in MLH1
gene expression. Finally, the mutant genotype AA of MLH1 was associated with a
significant decrease in the expression of this gene. This finding suggests that
this polymorphism could increase the risk of developing colorectal cancer by a
defective mismatch repair system, particularly through the loss of MLH1
expression in an allele-specific manner.
PMID- 25115747
TI - Effect of tele-emergency services on recruitment and retention of US rural
physicians.
AB - INTRODUCTION: As competition for physicians intensifies in the USA, rural areas
are at a disadvantage due to challenges unique to rural medical practice.
Telemedicine improves access to care not otherwise available in rural settings.
Previous studies have found that telemedicine also has positive effects on the
work environment, suggesting that telemedicine may improve rural physician
recruitment and retention, although few have specifically examined this. METHODS:
Using a mixed-method approach, clients of a single telemedicine service in the
Upper Midwestern USA were surveyed and interviewed about their views of the
impact of tele-emergency on physician recruitment and retention and the work
environment. Surveys were completed by 292 clinical and administrative staff at
71 hospitals and semi-structured interviews were conducted with clinicians and
administrators at 16 hospitals. RESULTS: Survey respondents agreed that tele
emergency had a positive effect on physician recruitment and retention and
related workplace factors. Interviewees elucidated how the presence of tele
emergency played an important role in enhancing physician confidence, providing
educational opportunities, easing burden, and supplementing care, workplace
factors that interviewees believed would impact recruitment and retention.
However, gains were limited by hospitals' interpretation of the Emergency Medical
Treatment and Labor Act as requiring on-site physician coverage even if tele
emergency was used. CONCLUSIONS: Results indicate that, all other factors being
equal, tele-emergency increases the likelihood of physicians entering and
remaining in rural practice. New regulatory guidance by the Centers for Medicare
and Medicaid Services related to on-site physician coverage will likely
accelerate implementation of tele-emergency services in rural hospitals.
Telemedicine may prove to be an increasingly valuable recruitment and retention
tool for rural hospitals as competition for physicians intensifies.
PMID- 25115749
TI - Mortality study of civilian employees exposed to contaminated drinking water at
USMC Base Camp Lejeune: a retrospective cohort study.
AB - BACKGROUND: Two drinking water systems at U.S. Marine Corps Base Camp Lejeune,
North Carolina were contaminated with solvents during 1950s-1985. METHODS: We
conducted a retrospective cohort mortality study of 4,647 civilian, full-time
workers employed at Camp Lejeune during 1973-1985 and potentially exposed to
contaminated drinking water. We selected a comparison cohort of 4,690 Camp
Pendleton workers employed during 1973-1985 and unexposed to contaminated
drinking water. Mortality follow-up period was 1979-2008. Cause-specific
standardized mortality ratios utilized U.S. age-, sex-, race-, and calendar
period-specific mortality rates as reference. We used survival analysis to
compare mortality rates between Camp Lejeune and Camp Pendleton workers and
assess the effects of estimated cumulative contaminant exposures within the Camp
Lejeune cohort. Ground water contaminant fate/transport and distribution system
models provided monthly estimated contaminant levels in drinking water serving
workplaces at Camp Lejeune. The confidence interval (CI) indicated precision of
effect estimates. RESULTS: Compared to Camp Pendleton, Camp Lejeune workers had
mortality hazard ratios (HRs) >1.50 for kidney cancer (HR = 1.92, 95% CI: 0.58,
6.34), leukemias (HR = 1.59, 95% CI: 0.66, 3.84), multiple myeloma (HR = 1.84,
95% CI: 0.45, 7.58), rectal cancer (HR = 1.65, 95% CI: 0.36, 7.44), oral cavity
cancers (HR = 1.93, 95% CI: 0.34, 10.81), and Parkinson's disease (HR = 3.13, 95%
CI: 0.76, 12.81). Within the Camp Lejeune cohort, monotonic exposure-response
relationships were observed for leukemia and vinyl chloride and PCE, with
mortality HRs at the high exposure category of 1.72 (95% CI: 0.33, 8.83) and 1.82
(95% CI: 0.36, 9.32), respectively. Cumulative exposures were above the median
for most deaths from cancers of the kidney, esophagus, rectum, prostate, and
Parkinson's disease, but small numbers precluded evaluation of exposure-response
relationships. CONCLUSION: The study found elevated HRs in the Camp Lejeune
cohort for several causes of death including cancers of the kidney, rectum, oral
cavity, leukemias, multiple myeloma, and Parkinson's disease. Only 14% of the
Camp Lejeune cohort died by end of follow-up, producing small numbers of cause
specific deaths and wide CIs. Additional follow-up would be necessary to
comprehensively assess drinking water exposure effects at the base.
PMID- 25115760
TI - A Seeming Paradox: Ischemic Stroke in the Context of Idiopathic Thrombocytopenic
Purpura.
AB - Nowadays, we have a relatively sophisticated standard approach to a patient with
acute ischemic stroke, including the sequence of diagnostic methods and treatment
modalities. In practice, however, we are occasionally confronted with a patient
whose medical history or comorbidities force us to make a decision without the
support of guidelines. One such situation is the occurrence of acute ischemic
stroke in a patient with known idiopathic thrombocytopenic purpura, where a
tendency to use thrombolysis, anticoagulants, or antiplatelet agents collides
with the fear of life-threatening bleeding. In this review, we try to outline
current understanding of the pathophysiology of "paradoxical" ischemic events in
this illness characterized by thrombocytopenia and to summarize clinical
experience from case reports dealing with this topic, which could help us to rely
on more than individual opinion seen through a purely "neurological" or
"hematological" prism.
PMID- 25115748
TI - Hippocampal volume mediates the relationship between measures of pre-treatment
cocaine use and within-treatment cocaine abstinence.
AB - BACKGROUND: Data suggest that the amygdala and hippocampus contribute to cocaine
seeking and use, particularly following exposure to cocaine-related cues and
contexts. Furthermore, indices of pre-treatment cocaine-use severity have been
shown to correlate with treatment outcome in cocaine-dependent patients. METHODS:
The aim of this study was to assess the relationships between amygdalar and
hippocampal volumes and cocaine use before and during treatment. High-resolution
magnetic-resonance brain images were obtained from 23 cocaine-dependent patients
prior to treatment and 54 healthy comparison individuals. Automated segmentation
of the amygdala and hippocampus images was performed in FreeSurfer. Cocaine
dependent patients subsequently received behavioral therapy alone or combined
with contingency management as part of a treatment trial, and cocaine-use indices
(self-report, urine toxicology) were collected. RESULTS: Comparison participants
and cocaine-dependent patients did not show significant difference in amygdalar
and hippocampal volumes at pre-treatment. Within the patient group, greater
hippocampal volumes were correlated with more days of cocaine use before
treatment and with poorer treatment outcome as indexed by shorter durations of
continuous abstinence from cocaine and lower percentages of cocaine-negative
urine samples during treatment. Mediation analysis indicated that pre-treatment
hippocampal volumes mediated the relationships between pre-treatment cocaine use
and treatment outcomes. CONCLUSIONS: The finding of a significant correlation
between hippocampal volume and pre-treatment cocaine-use severity and treatment
response suggests that hippocampal volume should be considered when developing
individualized treatments for cocaine dependence.
PMID- 25115759
TI - Role of Nrf2/ARE pathway in protective effect of electroacupuncture against
endotoxic shock-induced acute lung injury in rabbits.
AB - NF-E2 related factor 2 (Nrf2) is a major transcription factor and acts as a key
regulator of antioxidant genes to exogenous stimulations. The aim of current
study was to determine whether Nrf2/ARE pathway is involved in the protective
effect of electroacupuncture on the injured lung in a rabbit model of endotoxic
shock. A dose of lipopolysaccharide (LPS) 5 mg/kg was administered intravenously
to replicate the model of acute lung injury induced by endotoxic shock.
Electroacupuncture pretreatment was handled bilaterally at Zusanli and Feishu
acupoints for five consecutive days while sham electroacupuncture punctured at
non-acupoints. Fourty anesthetized New England male rabbits were randomized into
normal control group (group C), LPS group (group L), electroacupuncture + LPS
group (group EL) and sham electroacupuncture + LPS (group SEL). At 6 h after LPS
administration, the animals were sacrificed and the blood samples were collected
for biochemical measurements. The lungs were removed for calculation of wet-to
dry weight ratios (W/D), histopathologic examination, determination of heme
oxygenase (HO)-1 protein and mRNA, Nrf2 total and nucleoprotein, as well as Nrf2
mRNA expression, and evaluation of the intracellular distribution of Nrf2
nucleoprotein. LPS caused extensive morphologic lung damage, which was lessened
by electroacupuncture treatment. Besides, lung W/D ratios were significantly
decreased, the level of malondialdehyde was inhibited, plasma levels of TNF-alpha
and interleukin-6 were decreased, while the activities of superoxide dismutase,
glutathione peroxidase and catalase were enhanced in the electroacupucnture
treated animals. In addition, electroacupuncture stimulation distinctly increased
the expressions of HO-1 and Nrf2 protein including Nrf2 total protein and
nucleoprotein as well as mRNA in lung tissue, while these effects were blunted in
the sham electroacupuncture group. We concluded that electroacupuncture treatment
at ST36 and BL13 effectively attenuates lung injury in a rabbit model of
endotoxic shock through activation of Nrf2/ARE pathway and following up
regulation of HO-1 expression.
PMID- 25115761
TI - Sustained release of tissue factor following thrombosis of lower limb trauma.
AB - This study was undertaken to provide evidence for the mechanism of venous
thromboembolism (VTE) in healthy patients with minor lower limb injury (fracture;
Achilles tendon rupture) that was medically managed with plaster cast/brace
immobilization. The Plaster Cast clinical trial provided a unique opportunity to
identify the natural history of VTE using placebo-controlled patients (n = 183)
with validation of the mechanism using the low-molecular-weight heparin (LMWH;
reviparin)-treated patients (n = 182). Confirmed VTE in this population was
associated with a burst of tissue factor release (and a minor fibrinolytic
deficit) leading to thrombin generation that was sustained at least 5 weeks,
greater with fractures than with soft-tissue injuries and greater with surgery
than with conservative treatment. The root cause likely involves
platelet/leukocyte activation (inflammation) rather than endothelial cell injury.
Thromboprophylaxis with a low dose of LMWH reduced thrombin generation, with
patients undergoing surgery benefitting the most.
PMID- 25115762
TI - Oral anticoagulants and status of antidotes for the reversal of bleeding risk.
AB - Anticoagulants have been used in clinical practice for more than 50 years. Their
indications expand, as more people are diagnosed each year with atrial
fibrillation and venous thromboembolism. Vitamin K antagonists have been the most
popular choice due to their effectiveness and their ability to reverse bleeding
using a known antidote; oral and intravenous vitamin K have long been known to
reverse the effects of warfarin. With new classes of anticoagulants making their
way onto the market, such as factor Xa inhibitors (rivaroxaban, apixaban) and
direct thrombin inhibitors (dabigatran), the need for new reversal agents is
paramount. Patients tend to be more receptive to these medications because they
do not require routine blood monitoring, can be used at fixed doses, and do not
have major drug or food interactions. Antidotes for these medications have shown
promise in animal models and are currently in clinical trials.
PMID- 25115763
TI - Oxidative Stress and Spontaneous Reperfusion of Infarct-Related Artery in
Patients With ST-Segment Elevation Myocardial Infarction.
AB - In the pathogenesis of atherosclerosis, oxidative stress plays a major role in
plaque instability, rupture, and erosion, which subsequently leads to thrombus
formation and causes total infarct-related artery (IRA) occlusion. We
investigated the relationship between spontaneous reperfusion (SR) of IRA and
oxidative stress in patients with anterior ST-segment elevation myocardial
infarction (STEMI) undergoing primary percutaneous coronary intervention. A total
of 341 consecutive patients with anterior STEMI were prospectively included in
the present study. Patients were divided into 2 groups according to their
thrombolysis in myocardial infarction (TIMI) flow grade: SR group (66 patients,
TIMI flow 3) and non-SR group (275 patients, TIMI flow 0-2). On multivariate
logistic regression analysis, oxidative stress index (beta = 0.868, 95%
confidence interval [CI] = 0.806-0.934, P < .001), neutrophil to lymphocyte
ratio, uric acid, mean platelet volume, Killip 2 to 4 class, and initial SYNTAX
score were independently associated with SR. Oxidative stress as well as
inflammation may play a pivotal role in the pathogenesis of SR in patients with
STEMI.
PMID- 25115764
TI - Dabigatran Versus Warfarin in Atrial Fibrillation: Multicenter Experience in
Turkey.
AB - Safety issues have been raised about dabigatran. We aimed to investigate the
occurrence of safety outcomes in patients who had atrial fibrillation and a risk
of stroke. We analyzed 439 patients prescribed dabigatran (n = 220) or warfarin
(n = 219). Ischemic stroke occurred in 15 (6.8%) patients in the warfarin group
versus 5 (5.2%) patients in the 110-mg group versus 1 (0.8%) patient in the 150
mg dabigatran group (P = .015). Intracranial hemorrhage occurred in 6 (2.7%)
patients in the warfarin group versus 3 (2.4%) patients in the 150-mg dabigatran
group (P = .104). Death from any cause occurred in 10 (4.6%) patients in the
warfarin group versus 1 (1.0%) patient in the 110-mg dabigatran group (P = .005).
Dabigatran was associated with less ischemic stroke and death from any cause than
warfarin. Dabigatran may be a better option for stroke prophylaxis, where
recommended monitoring with warfarin is suboptimal.
PMID- 25115765
TI - High-resolution ultrasound allows percutaneous initiation and surveillance of
prostate cancer in an orthotopic murine model.
AB - INTRODUCTION: Prostate cancer xenografts should prefer orthotopic growth to
subcutaneous tumors as the former more closely mimics the natural tumor
environment. However, these models are technically demanding and require an
invasive laparotomy. To overcome these problems, we evaluated a minimally
invasive approach by performing percutaneous prostate puncture under the control
of high-resolution ultrasound imaging. MATERIALS AND METHODS: Orthotopic tumor
cell inoculation was performed in two groups of mice, i.e. in 10 nude mice via
ultrasound-guided inoculation and in another 10 nude mice via an open surgical
approach. Tumor growth was monitored after 4, 5 and 6 weeks by means of a high
resolution ultrasound system. RESULTS: High-resolution ultrasound allowed exact
tumor growth monitoring. After ultrasound-guided inoculation, 8 of 10 animals
showed tumor engraftment. The surgical procedure was successful in 9 of 10
animals. Tumor volume was slightly but not significantly greater after surgical
tumor induction. Our work demonstrates that tumor cell inoculation via
percutaneous puncture of the prostate is feasible, less time-consuming and
minimally invasive compared to an open surgical approach. This reduces the animal
burden. CONCLUSION: Although the tumor size and the precision of inoculation is
lower compared to the open surgical technique, this novel procedure enables real
time prostate punctures, suggesting the feasibility of other procedures including
biopsy and local drug applications.
PMID- 25115767
TI - Robotics and regional anesthesia.
AB - PURPOSE OF REVIEW: Robots in regional anesthesia are used as a tool to automate
the performance of regional techniques reducing the anesthesiologist's workload
and improving patient care. The purpose of this review is to show the latest
findings in robotic regional anesthesia. RECENT FINDINGS: The literature
separates robots in anesthesia into two groups: pharmacological robots and manual
robots. Pharmacological robots are mainly closed-loop systems that help in the
titration of anesthetic drugs to patients undergoing surgery. Manual robots are
mechanical robots that are used to support or replace the manual gestures
performed by anesthesiologists. Although in the last decade researchers have
focused on the development of decision support systems and closed-loop systems,
more recent evidence supports the concept that robots can also be useful in
performing regional anesthesia techniques. SUMMARY: Robots can improve the
performance and safety in regional anesthesia. In this review, we present the
developments made in robotic and automated regional anesthesia, and discuss the
current state of research in this field.
PMID- 25115766
TI - Postoperative ICU management of patients after subarachnoid hemorrhage.
AB - PURPOSE OF REVIEW: This article reviews recent advances in the postoperative ICU
management of patients after subarachnoid hemorrhage (SAH), especially with
regards to hemodynamic management, methods of improving neurological outcomes,
and management of cardiac and pulmonary complications. RECENT FINDINGS: Several
hemodynamic monitors and parameters may be useful for guiding volume therapy,
including cardiac output, stroke volume variation monitoring, and global end
diastolic volume index. Early goal-directed hemodynamic therapy after SAH has
recently been shown to improve clinical outcomes in patients with a poor clinical
grade or coexisting cardiopulmonary complications. Recent laboratory and imaging
modalities are being developed to identify patients at risk for developing
vasospasm after SAH. Evidence for the use of various prophylactic adjuvant
therapies to prevent vasospasm, including magnesium, phosphodiesterase 3
inhibitors, and therapeutic hypothermia, is emerging. Intrathecal administration
of vasodilators or fibrinolytics may have offered advantages over systemic drug
administration in the treatment of vasospasm. Pulmonary and cardiac complications
are common after SAH, and are associated with an increased risk of mortality.
SUMMARY: The postoperative ICU period after SAH is associated with a significant
morbidity and mortality risk, and recent studies have greatly contributed to our
understanding of how to optimally manage these patients.
PMID- 25115768
TI - Bioactive constituents from Croton sparsiflorus Morong.
AB - Whole plant extracts of Croton sparsiflorus in methanol have shown significant
enzyme inhibition and antioxidant activities. Bioassay-guided isolation of
chloroform fraction at pH 3 resulted in the identification of crotsparinine (1)
and crotsparine (2), while sparsiflorine (3) was purified from the chloroform
fraction at pH 9. The structures of the compounds were confirmed through spectral
analyses (EI-MS, (1)H and (13)C NMR). The isolated compounds 1-3 exhibited
remarkable enzyme inhibition activity with IC50 values 27.01 +/- 1.1, 22.26 +/-
1.0 and 18.02 +/- 1.3 MUM in xanthine oxidase and 48.42 +/- 1.5, 48.05 +/- 1.4
and 7.42 +/- 1.0 MUM in acetylcholine esterase assays, respectively. These
compounds also showed potent radical scavenging and reducing properties in DPPH
and FRAP assays, respectively. The present results suggest the validity of the
traditional uses of C. sparsiflorus in rheumatism and gout. Furthermore, the
isolated noraporphine alkaloids can be useful in the treatment of
neurodegenerative diseases.
PMID- 25115769
TI - Echocardiographic factors discriminating biventricular versus univentricular
approach in the foetus with borderline left ventricle.
AB - BACKGROUND: The term "borderline left ventricle" describes a small left heart
that may be inadequate to provide systemic cardiac output and implies the
potential need for a single-ventricle palliation. The aim of this study was to
identify foetal echocardiographic features that help discriminate which infants
will undergo single-ventricle palliation versus biventricular repair to aid in
prenatal counselling. METHODS: The foetal database at our institution was
searched to identify all foetuses with borderline left ventricle, as determined
subjectively by a foetal cardiologist, from 2000 to 2011. The foetal images were
retrospectively analysed for morphologic and physiologic features to determine
which best predicted the postnatal surgical choice. RESULTS: Of 39 foetuses
identified with borderline left ventricle, 15 were planned for a univentricular
approach, and 24 were planned for a biventricular approach. There were
significant differences between the two outcome groups in the Z-scores of the
mitral valve annulus, left ventricular end-diastolic dimension, aortic valve
annulus, and ascending aorta diameter (p<0.05). With respect to discriminating
univentricular outcomes, cut-offs of mitral valve Z-score ?-1.9 and
tricuspid:mitral valve ratio ?1.5 were extremely sensitive (100%), whereas a
right:left ventricular end-diastolic dimension ratio ?2.1 provided the highest
specificity (95.8%). CONCLUSION: In foetuses with borderline left ventricle, a
mitral valve Z-score ?-1.9 or a tricuspid:mitral valve ratio ?1.5 suggests a high
probability of biventricular repair, whereas a right:left ventricular end
diastolic dimension ratio ?2.1 confers a likelihood of single-ventricle
palliation.
PMID- 25115770
TI - Draft genome sequences of three Holospora species (Holospora obtusa, Holospora
undulata, and Holospora elegans), endonuclear symbiotic bacteria of the ciliate
Paramecium caudatum.
AB - We present draft genome sequences of three Holospora species, hosted by the
ciliate Paramecium caudatum; that is, the macronucleus-specific H. obtusa and the
micronucleus-specific H. undulata and H. elegans. We investigate functions of
orthologous core genes conserved across the three Holospora species, which may be
essential for the infection and survival in the host nucleus.
PMID- 25115771
TI - Lamina cribrosa displacement after optic nerve sheath fenestration in idiopathic
intracranial hypertension: a new tool for monitoring changes in intracranial
pressure?
PMID- 25115772
TI - The effect of glucagon-like peptide-1 in the management of diabetes mellitus:
cellular and molecular mechanisms.
AB - Incretins, such as glucagon-like peptide-1 (GLP)-1, have been shown to elevate
plasma insulin concentration. The purpose of this study is to investigate the
cellular and molecular basis of the beneficial effects of GLP-1. Normal and
diabetic male Wistar rats were treated with GLP-1 (50 ng/kg body weight) for 10
weeks. At the end of the experiment, pancreatic tissues were taken for
immunohistochemistry, immunoelectron microscopy and real-time polymerase chain
reaction studies. Samples of blood were retrieved from the animals for the
measurement of enzymes and insulin. The results show that treatment of diabetic
rats with GLP-1 caused significant (P < 0.05) reduction in body weight gain and
blood glucose level. GLP-1 (10(-12)-10(-6) M) induced significant (P < 0.01) dose
dependent increases in insulin release from the pancreas of normal and diabetic
rats compared to basal. Diabetes-induced abnormal liver (aspartate
aminotransferase and alanine aminotransferase) and kidney (blood urea nitrogen
and uric acid) parameters were corrected in GLP-1-treated rats compared to
controls. GLP-1 treatment induced significant (P < 0.05) elevation in the
expression of pancreatic duodenal homeobox-1, heat shock protein-70, glutathione
peroxidase, insulin receptor and GLP-1-receptor genes in diabetic animals
compared to controls. GLP-1 is present in pancreatic beta cells and significantly
(P < 0.05) increased the number of insulin-, glutathione reductase- and catalase
immunoreactive islet cells. The results of this study show that GLP-1 is co
localized with insulin and seems to exert its beneficial effects by increasing
cellular concentrations of endogenous antioxidant genes and other genes involved
in the maintenance of pancreatic beta cell structure and function.
PMID- 25115773
TI - Effects of sildenafil on nanostructural and nanomechanical changes in
mitochondria in an ischaemia-reperfusion rat model.
AB - Sildenafil exerts cardioprotective effects by activating the opening of
mitochondrial ATP-sensitive potassium channels to attenuate ischaemia-reperfusion
(IR) injury. In the present study, we used atomic force microscopy (AFM) to
investigate changes in mitochondrial morphology and properties to assess
sildenafil-mediated cardioprotection in a rat myocardial infarction model. To
investigate the cardioprotective effects of sildenafil, we used an in vivo
Sprague-Dawley rat model of IR. Rats were randomly divided into three groups: (i)
sham-operated rats (control; n = 5); (ii) IR-injured rats treated with vehicle
(normal saline; IR; n = 10); and (iii) IR-injured rats treated with 0.75 mg/kg,
i.p., sildenafil (IR + Sil; n = 10). Morphological and mechanical changes to
mitochondria were analysed by AFM. Infarct areas were significantly reduced in
sildenafil-treated rats (7.8 +/- 3.9% vs 20.4 +/- 7.0% in the sildenafil-treated
and untreated IR groups, respectively; relative reduction 62%; P < 0.001).
Analysis of mitochondria by AFM showed that IR injury significantly increased the
areas of isolated mitochondria compared with control (24 150 +/- 18 289 vs 1495
+/- 1139 nm(2) , respectively; P < 0.001), indicative of mitochondrial swelling.
Pretreatment with sildenafil before IR injury reduced the mitochondrial areas
(7428 +/- 3682 nm(2) ; P < 0.001; relative reduction 69.2% compared with the IR
group) and ameliorated the adhesion force of mitochondrial surfaces. Together,
these results suggest that sildenafil has cardioprotective effects against IR
injury in a rat model by improving the morphological and mechanical
characteristics of mitochondria.
PMID- 25115774
TI - GFP stable transfection facilitated the characterization of lung cancer stem
cells.
AB - Cancer stem cells (CSCs) are a subset of cancer cells that play key roles in
metastasis and cancer relapse. The elimination of CSCs is very important during
cancer therapy. To develop drugs that target CSCs, the isolation and
identification of putative CSCs are required. Some of the characteristics of CSCs
are assessed by cell survival assays. In such experiments, the density of the
cells seeded on the plates may affect the experimental results, leading to
potentially inaccurate conclusions. In this study, a new assay to facilitate the
characterization of CSCs has been developed by stable transfection of GFP, using
the A549 lung cancer cell line as a model. A putative CSC line, A549 sphere
cells, was obtained by culturing A549 cells in ultra-low dishes in serum-free
medium. To ensure that the putative CSCs were grown under the same conditions as
the A549-GFP cells and were not affected by the number of cells seeded, A549
sphere cells were mixed with GFP stably transfected A549 (A549-GFP) cells. The
mixture was subjected to flow cytometry assay and inverted fluorescence
microscopy to detect changes in the proportion of GFP-positive cells after
treatment. A549 sphere cells had a slower proliferation rate and an improved
chemoresistance. They also showed differentiation ability. This work suggests
that mixing GFP stably transfected cancer cells with putative CSCs may facilitate
the identification of CSCs, making it convenient for studies of targeted CSCs.
PMID- 25115776
TI - Hydrogen bond mediated aglycone delivery: synthesis of linear and branched alpha
glucans.
AB - A Hydrogen bond mediated aglycone delivery (HAD) method was applied to the
synthesis of alpha-glucans, which are abundant in nature, but as targets
represent a notable challenge to chemists. The synthesis of linear
oligosaccharide sequences was accomplished in complete stereoselectivity in all
glycosylations. The efficacy of HAD may diminish with the increased bulk of the
glycosyl acceptor, and may be an important factor for the syntheses of oligomers
beyond pentasaccharides. The synthesis of a branched structure proved more
challenging, particularly with bulky trisaccharide acceptors.
PMID- 25115777
TI - On-line SERS detection of single bacterium using novel SERS nanoprobes and a
microfluidic dielectrophoresis device.
AB - The integration of novel surface-enhanced Raman scattering (SERS) nanoprobes and
a microfluidic dielectrophoresis (DEP) device is developed for rapid on-line SERS
detection of Salmonella enterica serotype Choleraesuis and Neisseria lactamica.
The SERS nanoprobes are prepared by immobilization of specific antibody onto the
surface of nanoaggregate-embedded beads (NAEBs), which are silica-coated, dye
induced aggregates of a small number of gold nanoparticles (AuNPs). Each NAEB
gives highly enhanced Raman signals owing to the presence of well-defined
plasmonic hot spots at junctions between AuNPs. Herein, the on-line SERS
detection and accurate identification of suspended bacteria with a detection
capability down to a single bacterium has been realized by the NAEB-DEP-Raman
spectroscopy biosensing strategy. The practical detection limit with a
measurement time of 10 min is estimated to be 70 CFU mL(-1) . In comparison with
whole-cell enzyme-linked immunosorbent assay (ELISA), the SERS-nanoprobe-based
biosensing method provides advantages of higher sensitivity and requiring lower
amount of antibody in the assay (100-fold less). The total assay time including
sample pretreatment is less than 2 h. Hence, this sensing strategy is promising
for faster and effective on-line multiplex detection of single pathogenic
bacterium by using different bioconjugated SERS nanoprobes.
PMID- 25115775
TI - Association between CYP1A2 and CYP1B1 polymorphisms and colorectal cancer risk: a
meta-analysis.
AB - BACKGROUND: The previous published data on the association between CYP1A2*F
(rs762551), CYP1B1 Leu432Val (rs1056836), Asn453Ser (rs180040), and Arg48Gly
(rs10012) polymorphisms and colorectal cancer risk remained controversial.
METHODOLOGY/PRINCIPAL FINDINGS: The purpose of this study is to evaluate the role
of CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly genotypes in colorectal
cancer susceptibility. We performed a meta-analysis on all the eligible studies
that provided 5,817 cases and 6,544 controls for CYP1A2*F (from 13 studies), 9219
cases and 10406 controls for CYP1B1 Leu432Val (from 12 studies), 6840 cases and
7761 controls for CYP1B1 Asn453Ser (from 8 studies), and 4302 cases and 4791
controls for CYP1B1Arg48Gly (from 6 studies). Overall, no significant association
was found between CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly and
colorectal cancer risk when all the eligible studies were pooled into the meta
analysis. And in the subgroup by ethnicity and source of controls, no evidence of
significant association was observed in any subgroup analysis.
CONCLUSIONS/SIGNIFICANCE: In summary, this meta-analysis indicates that CYP1A2*F,
CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly polymorphisms do not support an
association with colorectal cancer, and further studies are needed to investigate
the association. In addition, our work also points out the importance of new
studies for CYP1A2*F polymorphism in Asians, because high heterogeneity was found
(dominant model: I(2) = 81.3%; heterozygote model: I(2) = 79.0).
PMID- 25115778
TI - Short bowel syndrome and clopidogrel non-responsiveness: a new indication for
platelet aggregometry?
PMID- 25115779
TI - Asymptomatic coronary artery spasm with acute pathological ST elevation on
routine ECG: is it common?
AB - Asymptomatic spontaneous coronary artery spasm is rare and there are no case
reports in literature presenting with acute ST elevation on routine ECG. We
present the case of a 68-year-old Caucasian man who presented to a primary care
physician for a routine ECG as part of hypertension follow-up. ECG revealed ST
elevation in inferior leads II, III and aVF with reciprocal ST depression in
leads I, aVL and also ST depression in anterior leads V1, V2 and V3 suggesting
ongoing inferoposterior ST elevation myocardial infarction. The patient was
completely well, stable and asymptomatic and he was rushed immediately to the
coronary care unit via emergency ambulance. The patient was subjected to a
battery of urgent investigations which were all normal. Also an urgent coronary
angiogram was undertaken which showed completely normal coronary anatomy.
PMID- 25115780
TI - Completely calcified non-functioning kidney: a classical image of putty kidney.
PMID- 25115781
TI - Beneficial effects of growth hormone therapy for ossification defects after bone
distraction in X linked hypophosphataemic rickets.
AB - A report on two homozygous twin girls affected by X linked hypophosphataemic
rickets. They were examined due to short stature and genu varum of both tibias.
They were treated with calcitriol and Joulie's solution, whereon it was observed
that serum parathyroid hormone and phosphaturia decreased while phosphataemia
increased. They underwent a tibial osteotomy (by means of the insertion of
Kirchner needles) at 7.7 years of age for correction of genu varum and a normal
consolidation was reached 1 month later. Nonetheless, height was percentile <1
after menarche, so both sisters asked for bone lengthening. Because of this, at
15 years of age femoral distraction was performed, but no bone callus was
observed 14 months later. Consequently, they were treated with subcutaneous
growth hormone, showing bone callus at 6 months. Finally, the external fixators
were removed due to ossification in the lengthened segments.
PMID- 25115784
TI - Bilateral extraocular muscle (EOM) metastases from adenocarcinoma of the gastro
oesophageal junction (GOJ).
PMID- 25115783
TI - Methaemoglobinaemia in a G6PD-deficient child treated with rasburicase.
AB - A 5-year-old boy from the Congo, was admitted for hyperleucocytic acute
lymphoblastic leukaemia, with a high risk of tumour lysis syndrome (TLS). He had
splenomegaly and mediastinal lymphadenopathy on chest X-ray. We started steroids
and hyperhydration with rasburicase to prevent TLS. Respiratory failure with
mediastinal enlargement developed rapidly. A few hours after intensive care unit
(ICU) admission, he was started on mechanical ventilation. Chemotherapy was
started immediately given the strong suspicion of mediastinal compression. Low
oxygen saturation with high partial arterial oxygen pressure persisted. Blood
tests confirmed 20% methaemoglobinaemia and glucose-6-phosphate dehydrogenase
(G6PD) deficiency. Allopurinol was substituted for rasburicase. The
methaemoglobinaemia disappeared rapidly and he was discharged from the ICU after
72 h. In case of rasburicase use, a close clinical monitoring is mandatory,
especially in populations where G6PD deficiency is highly prevalent.
Methaemoglobinaemia must be suspected in case of low oxygen saturation when all
other potential causes have been ruled out.
PMID- 25115782
TI - Severe agitation in depression precipitated by dasatinib.
AB - We describe a case of a man with chronic myeloid leukaemia who achieved remission
through dasatinib therapy after being unable to tolerate several tyrosine kinase
inhibitor (TKI) regimens due to severe physical side effects. However, this
coincided with the onset of distressing agitation, insomnia and motor
restlessness leading him to take a large zopiclone overdose. Start of appropriate
therapy with a clonazepam, venlafaxine and mirtazapine combination led to a rapid
improvement in symptomatology. We discuss the differential diagnosis and review
the literature of neuropsychiatric complications of TKIs. This case serves as an
illustrative reminder that in cases of complicated agitation referral to
specialist mental health teams for rational psychopharmacological management is
advised.
PMID- 25115785
TI - Kasabach-Merritt phenomenon in a neonatal kaposiform haemangioendothelioma.
PMID- 25115786
TI - Dissemination of plasmid-encoded AmpC beta-lactamases in antimicrobial resistant
Salmonella serotypes originating from humans, pigs and the swine environment.
AB - The aim of this study was to characterize and determine the inter-serovar
exchange of AmpC beta-lactamase conferring plasmids isolated from humans, pigs
and the swine environment. Plasmids isolated from a total of 21 antimicrobial
resistant (AMR) Salmonella isolates representing human clinical cases (n=6), pigs
(n=6) and the swine farm environment (n=9) were characterized by replicon typing
and restriction digestion, inter-serovar transferability by conjugation, and
presence of AmpC beta-lactamase enzyme encoding gene blaCMY-2 by southern
hybridization. Based on replicon typing, the majority (17/21, 81%) of the
plasmids belonged to the I1-Igamma Inc group and were between 70 and 103kb. The
potential for inter-serovar plasmid transfer was further confirmed by the PCR
detection of AMR genes on the plasmids isolated from trans-conjugants. Plasmids
from Salmonella serovars Anatum, Ouakam, Johannesburg and Typhimurium isolated
from the same cohort of pigs and their environment and S. Heidelberg from a
single human clinical isolate had identical plasmids based on digestion with
multiple restriction enzymes (EcoRI, HindIII and PstI) and southern blotting. We
demonstrated likely horizontal inter-serovar exchange of plasmid-encoding AmpC
beta-lactamases resistance among MDR Salmonella serotypes isolated from pigs,
swine farm environment and clinical human cases. This study provides valuable
information on the role of the swine farm environment and by extension other
livestock farm environments, as a potential reservoir of resistant bacterial
strains that potentially transmit resistance determinants to livestock, in this
case, swine, humans and possibly other hosts by horizontal exchange of plasmids.
PMID- 25115787
TI - Identification and typing of Brucella spp. in stranded harbour porpoises
(Phocoena phocoena) on the Dutch coast.
AB - The presence of Brucella (B.) spp. in harbour porpoises stranded between 2008 and
2011 along the Dutch coast was studied. A selection of 265 tissue samples from
112 animals was analysed using conventional and molecular methods. In total, 4.5%
(5/112) of the animals corresponding with 2.3% (6/265) Brucella positive tissue
samples were Brucella positive by culture and these were all confirmed by real
time polymerase chain reaction (real-time PCR) based on the insertion element 711
(IS711). In addition, two more Brucella-positive tissue samples from two animals
collected in 2011 were identified using real-time PCR resulting in an overall
Brucella prevalence of 6.3% (7/112 animals). Brucella spp. were obtained from
lungs (n=3), pulmonary lymph node (n=3) and lungworms (n=2). Multi Locus Variable
Number of Tandem Repeats (VNTR) Analysis (MLVA) typing based on the MLVA-16
showed that the Brucella isolates were B. ceti. Additional in silico Multi Locus
Sequence typing (MLST) after whole genome sequencing of the 6 Brucella isolates
confirmed B. ceti ST 23. According to the Brucella 2010 MLVA database, the
isolated Brucella strains encountered were of five genotypes, in two distinct
subclusters divided in two different time periods of harbour porpoises
collection. This study is the first population based analyses for Brucella spp.
infections in cetaceans stranded along the Dutch coast.
PMID- 25115788
TI - The effect of hyaluronic acid functionalized carbon nanotubes loaded with
salinomycin on gastric cancer stem cells.
AB - Gastric cancer stem cells (CSCs) play a crucial role in the initiation,
development, relapse and metastasis of gastric cancer because they are resistant
to a standard chemotherapy and the residual CSCs are able to proliferate
indefinitely. Therefore, eradication of this cell population is a primary
objective in gastric cancer therapy. Here, we report a gastric CSCs-specifically
targeting drug delivery system (SAL-SWNT-CHI-HA complexes) based on chitosan(CHI)
coated single wall carbon nanotubes (SWNTs) loaded with salinomycin (SAL)
functionalized with hyaluronic acid (HA) can selectively eliminate gastric CSCs.
Gastric CSCs were identified as CD44+ cells and cultured in serum-free medium.
SAL-SWNT-CHI-HA complexes were capable of inhibiting the self-renewal capacity of
CD44+ population, and decrease mammosphere- and colon-formation of CSCs. In
addition, the migration and invasion of gastric CSCs were significantly blocked
by SAL-SWNT-CHI-HA complexes. Quantitative and qualitative analysis of cellular
uptake demonstrated that HA functionalization facilitated the uptake of SWNTs in
gastric CSCs while free HA competitively inhibited cellular uptake of SAL-SWNT
CHI-HA delivery system, revealing the mechanism of CD44 receptor-mediated
endocytosis. The SAL-SWNT-CHI-HA complexes showed the strongest antitumor
efficacy in gastric CSCs by inducing apoptosis, and in CSCs mammospheres by
penetrating deeply into the core. Taken altogether, our studies demonstrated that
this gastric CSCs-targeted SAL-SWNT-CHI-HA complexes would provide a potential
strategy to selectively target and efficiently eradicate gastric CSCs, which is
promising to overcome the recurrence and metastasis of gastric cancer and improve
gastric cancer treatment.
PMID- 25115789
TI - Collagen mimetic peptide engineered M13 bacteriophage for collagen targeting and
imaging in cancer.
AB - Collagens are over-expressed in various human cancers and subsequently degraded
and denatured by proteolytic enzymes, thus making them a target for diagnostics
and therapeutics. Genetically engineered bacteriophage (phage) is a promising
candidate for the development of imaging or therapeutic materials for cancer
collagen targeting due to its promising structural features. We genetically
engineered M13 phages with two functional peptides, collagen mimetic peptide and
streptavidin binding peptide, on their minor and major coat proteins,
respectively. The resulting engineered phage functions as a therapeutic or
imaging material to target degraded and denatured collagens in cancerous tissues.
We demonstrated that the engineered phages are able to target and label abnormal
collagens expressed on A549 human lung adenocarcinoma cells after the conjugation
with streptavidin-linked fluorescent agents. Our engineered collagen binding
phage could be a useful platform for abnormal collagen imaging and drug delivery
in various collagen-related diseases.
PMID- 25115790
TI - Effects of two different rearing protocols for Holstein bull calves in the first
3 weeks of life on health status, metabolism and subsequent performance.
AB - The aim of this study was to investigate the impact of weight gain of calves
within the first 3 weeks of life on health status and subsequent performance.
Holstein bull calves were reared either intensively (IR; individual hutches and
ad libitum milk feeding for the first 3 weeks of life; n = 24), or according to
the established protocol [ER; 4 l milk/day in hutches during week 1 and 720 g/day
milk replacer (MR) from day 8 to 21 in a group pen; n = 24]. Water, hay and
concentrates were freely available to all calves. From week 4, calves of both
groups were housed together in a group pen and fed 720 g MR/day; step-down
weaning was performed between week 5 and 10. Key metabolic blood parameters were
analysed on day 2, 12, 21 and 70 of life. After weaning, all animals were fed
concentrates and corn silage until slaughter at an age of 8 months. Within the
first 3 weeks, average daily weight gain was threefold higher in IR calves in
relation to ER calves (1.28 vs. 0.38 kg/day, p < 0.001). Neither incidence nor
duration of scouring differed significantly between groups. Starter intake (week
4-10) was higher in IR calves in relation to ER calves (49.7 vs. 38.0 kg/calf, p
= 0.006). Serum glucose, urea, albumin and insulin were higher at an age of 21
days in IR calves in relation to ER calves; no differences were obvious at an age
of 70 days. Plasma GH and IGF-I concentrations revealed an uncoupling of the
somatotropic axis in ER calves within the first 3 weeks of life. At slaughter,
body weight of IR calves tended to be higher than that of the ER calves (320 vs.
309 kg, p = 0.07). In conclusion, intensive feeding and individual housing during
the first 3 weeks of life had positive long-term effects on subsequent
performance.
PMID- 25115791
TI - Social participation of school-aged children who use communication aids: the
views of children and parents.
AB - Social participation is crucial for children's development and well-being;
however, little is known about the social participation of children who use
communication aids. This article presents findings from interviews with eight 5-
to 14-year-old children who used communication aids and their parents about
social participation, communicative interactions, and peer relationships. Video-
and audio-recordings were transcribed and analyzed using thematic content
analysis, and five themes were identified. Two themes reflect parents' views:
Communication partners and strategies and Access to aided communication. Three
themes reflect perceptions expressed both by children and parents: Participation
in society, Interaction opportunities, and Social relationships. The findings
provide insights into both the achievements and the challenges experienced by
young people who use aided communication.
PMID- 25115794
TI - Two new cyclic dipeptides from Rhinocladiella sp. lgt-3, a fungal endophyte
isolated from Tripterygium wilfordii Hook.
AB - Two new cyclic dipeptides, rhinocladin A (1) and rhinocladin B (2), were isolated
from a fungal endophyte (Rhinocladiella sp. lgt-3) of Tripterygium wilfordii
Hook. Their structures were elucidated by 1D and 2D NMR spectra. The monoamine
oxidase inhibitory activity of 1 and 2 was also evaluated.
PMID- 25115795
TI - Fermented food in the context of a healthy diet: how to produce novel functional
foods?
AB - PURPOSE OF REVIEW: This review presents an overview of recent studies on the
production of functional fermented foods, of both traditional and innovative
natures, and the mapping of the functional compounds involved. RECENT FINDINGS:
The functional aspects of fermented foods are mostly related to the concept of
probiotic bacteria or the targeted microbial generation of functional molecules,
such as bioactive peptides, during food fermentation. Apart from conventional
yoghurt and fermented milks, several fermented nondairy foods are globally
gaining in interest, in particular from soy or cereal origin, sometimes novel but
often originating from ethnic (Asian) diets. In addition, a range of functional
nonmicrobial compounds may be added to the fermented food matrix. Overall, a wide
variety of potential health benefits is being claimed, yet often poorly supported
by mechanistic insights and rarely demonstrated with clinical trials or even
animal models. SUMMARY: Although functional foods offer considerable market
potential, several issues still need to be addressed. As most of the studies on
functional fermented foods are of a rather descriptive and preliminary nature,
there is a clear need for mechanistic studies and well controlled in-vivo
experiments.
PMID- 25115793
TI - The H3K9 methyltransferase G9a is a marker of aggressive ovarian cancer that
promotes peritoneal metastasis.
AB - BACKGROUND: Ovarian cancer (OCa) peritoneal metastasis is the leading cause of
cancer-related deaths in women with limited therapeutic options available for
treating it and poor prognosis, as the underlying mechanism is not fully
understood. METHOD: The clinicopathological correlation of G9a expression was
assessed in tumor specimens of ovarian cancer patients. Knockdown or
overexpression of G9a in ovarian cancer cell lines was analysed with regard to
its effect on adhesion, migration, invasion and anoikis-resistance. In vivo
biological functions of G9a were tested by i.p. xenograft ovarian cancer models.
Microarray and quantitative RT-PCR were used to analyze G9a-regulated downstream
target genes. RESULTS: We found that the expression of histone methyltransferase
G9a was highly correlated with late stage, high grade, and serous-type OCa.
Higher G9a expression predicted a shorter survival in ovarian cancer patients.
Furthermore, G9a expression was higher in metastatic lesions compared with their
corresponding ovarian primary tumors. Knockdown of G9a expression suppressed
prometastatic cellular activities including adhesion, migration, invasion and
anoikis-resistance of ovarian cancer cell lines, while G9a over-expression
promoted these cellular properties. G9a depletion significantly attenuated the
development of ascites and tumor nodules in a peritoneal dissemination model.
Importantly, microarray and quantitative RT-PCR analysis revealed that G9a
regulates a cohort of tumor suppressor genes including CDH1, DUSP5, SPRY4, and
PPP1R15A in ovarian cancer. Expression of these genes was also inversely
correlated with G9a expression in OCa specimens. CONCLUSION: We propose that G9a
contributes to multiple steps of ovarian cancer metastasis and represents a novel
target to combat this deadly disease.
PMID- 25115796
TI - Vocal behavior and vocal central pattern generator organization diverge among
toadfishes.
AB - Among fishes, acoustic communication is best studied in toadfishes, a single
order and family that includes species commonly known as toadfish and midshipman.
However, there is a lack of comparative anatomical and physiological studies,
making it difficult to identify both shared and derived mechanisms of
vocalization among toadfishes. Here, vocal nerve labeling and intracellular in
vivo recording and staining delineated the hindbrain vocal network of the Gulf
toadfish Opsanus beta. Dextran-biotin labeling of the vocal nerve or
intracellular neurobiotin fills of motoneurons delineated a midline vocal motor
nucleus (VMN). Motoneurons showed bilaterally extensive dendritic arbors both
within and lateral to the paired motor nuclei. The motoneuron activity matched
that of the spike-like vocal nerve motor volley that determines the natural call
duration and frequency. Ipsilateral vocal nerve labeling with biocytin or
neurobiotin yielded dense bilateral transneuronal filling of motoneurons and
coextensive columns of premotor neurons. These premotor neurons generated
pacemaker-like action potentials matched 1:1 with vocal nerve and motoneuron
firing. Transneuronal transport further revealed connectivity within and between
the pacemaker-motor circuit and a rostral prepacemaker nucleus. Unlike the
pacemaker-motor circuit, prepacemaker firing did not match the frequency of vocal
nerve activity but instead was predictive of the duration of the vocal nerve
volley that codes for call duration. Transneuronally labeled terminal-like
boutons also occurred in auditory-recipient hindbrain nuclei, including neurons
innervating the inner ear and lateral line organs. Together with studies of
midshipman, we propose that separate premotor populations coding vocal frequency
and duration with direct premotor coupling to auditory-lateral line nuclei are
plesiomorphic characters for toadfishes. Unlike in midshipman, transneuronal
labeling in toadfishes reveals an expansive column of pacemaker neurons that is
weakly coupled to prepacemaker neurons, a character that likely depends on the
extent of gap junction coupling. We propose that these and other anatomical
characters contribute to neurophysiological properties that, in turn, sculpt the
species-typical patterning of frequency and amplitude-modulated vocalizations.
PMID- 25115797
TI - Anthropometry and body composition of vertically HIV-infected children and
adolescents under therapy with and without protease inhibitors.
AB - OBJECTIVE: Although the benefits of highly active antiretroviral therapy (HAART)
have been documented, it is thought to be associated to disturbances in
nutritional status. These disturbances may occur early in life and are poorly
understood. The present study aimed to investigate the relationship between
anthropometric parameters and body composition of perinatally HIV-infected
children and adolescents under HAART, according to use and non-use of protease
inhibitors. DESIGN: Cross-sectional study undertaken between August and December
2007. Demographic, socio-economic, clinical and anthropometric data were
collected from the patients. The chi 2 test, Wilcoxon rank sum test (Mann
Whitney) and t test were used to compare the following variables between users
and non-users of protease inhibitors: age, gender, per capita income, HAART
exposure, antiretroviral therapy adopted in the last three years, CD4 count,
viral load, pubertal stage, nutritional status (BMI-for-age, height-for-age,
waist and neck circumferences, triceps skinfold thickness, body fat percentage,
upper-arm fat area and upper-arm muscle area). SETTING: An HIV/AIDS out-patient
clinic, Sao Paulo, Brazil. SUBJECTS: One hundred and fifteen patients (children
and adolescents aged 6-19 years). RESULTS: Protease inhibitors users had a higher
prevalence of stunting (P=0.03), lower BMI (P=0.03) and lower percentage of body
fat (P=0.05) compared with non-users. There was no statistically significant
difference between the HAART regimens and measurements of fat adiposity.
CONCLUSIONS: The findings of the study suggest that children and adolescents
under protease inhibitors are at higher risk of growth and development
deviations, but not at risk of body fat redistribution.
PMID- 25115798
TI - Occurrence of Treponema DNA in equine hoof canker and normal hoof tissue.
AB - REASONS FOR PERFORMING STUDY: Equine hoof canker is a chronic pododermatitis of
still unknown aetiology. Recent findings reported for 3 canker-bearing
individuals are suggestive for Treponema spp. having a role in disease
pathogenesis. OBJECTIVES: Based on this hypothesised association, we assessed a
larger number of DNA samples from hooves with canker and normal hooves for the
presence of treponemal DNA. STUDY DESIGN: Retrospective survey of archived
material. METHODS: The study involved 71 archival, PCR-compatible DNA extractions
purified from 59 canker samples obtained from 26 equine cases and from 12 hoof
biopsies taken from 9 canker-free control horses. Presence of treponemal DNA was
assessed by qualitative PCR using 4 different primer pairs recognising in sum a
broad range of Treponema ssp. Obtained amplification products were identified by
bidirectional sequencing and BLAST alignment. RESULTS: Treponemal DNA was
detected in 37 of 59 canker DNA samples from 19 of 26 cases and in 9 of 12 hoof
DNA samples from 7 of 9 healthy individuals. Canine oral Treponema sp. and
Treponema medium ssp. bovis were the most frequently detected treponemal
sequences in hoof canker, while control tissues were mainly shown to harbour
Treponema refringens-like or canine oral Treponema-like DNA. All control samples
tested negative for T. medium ssp. bovis DNA. CONCLUSIONS: Treponema DNA was
detectable in the majority of hoof canker and control samples. The sample groups
differed to some extent regarding identified Treponema phylotypes; however, this
finding may be explained by the methodology used. Treponemes that are highly
similar to bovine digital dermatitis treponemes are present in canker lesions.
However, further work is needed to clarify the specific contribution of the
identified Treponema phylotypes to the pathogenesis of disease.
PMID- 25115799
TI - Aerobic denitrification by Pseudomonas stutzeri C3 incapable of heterotrophic
nitrification.
AB - An aerobic denitrifier was isolated from activated sludge and the isolate
possessed an average nitrate removal efficiency of 95.8% in 24 h, with the
maximum nitrite accumulation of 25.6 mg/l. The bacterium could not conduct
heterotrophic nitrification. The results of PCR indicated that the strain lacked
the gene of amoA. The phylogenetic tree indicated a clear evolutionary divergence
that Pseudomonas stutzeri C3 belonged to the group of strains that could not
exhibit ammonia oxidation.
PMID- 25115801
TI - B-Type natriuretic peptide suppression of neutrophil superoxide generation:
mechanistic studies in normal subjects.
AB - Many acute cardiovascular disease states are associated with neutrophil
infiltration of myocardium and subsequent release of superoxide (O2 (-) ) and
myeloperoxidase (MPO), which contribute to inflammatory reactions. B-Type
natriuretic peptide (BNP) is known to exert anti-inflammatory and antifibrotic
effects, but it is not known whether these may include interactions with
neutrophils. In neutrophils isolated from 20 healthy subjects, we assessed the
effect of BNP on the 'neutrophil burst' (O2 (-) production and MPO release)
stimulated by phorbol myristate acetate (PMA) and N-formyl-methionyl-leucyl
phenylalanine (fMLP), respectively. Effects of BNP on cGMP accumulation, and the
effects of the cell-permeable cGMP analogue 8-(4-chlorophenylthio) guanosine-cGMP
(8-p-CPT-cGMP) and protein kinase G (PKG) inhibition with KT5823 on the
neutrophil-BNP interaction were also evaluated. B-Type natriuretic peptide
suppressed O2 (-) release from neutrophils by 23 +/- 6% (P < 0.001) and 24 +/- 8%
(P < 0.05) following PMA and fMLP stimulation, respectively. Although BNP did not
significantly increase cGMP formation, 8-p-CPT-cGMP suppressed both PMA- and fMLP
induced neutrophil O2 (-) release by 16% and 28%, respectively (P < 0.05). The
PKG inhibitor KT5823 attenuated the effects of BNP on both fMLP- and PMA
associated O2 (-) production. Neither BNP nor 8-p-CPT-cGMP significantly affected
MPO release from neutrophils. Suppression of O2 (-) release from neutrophils by
BNP may contribute to its anti-inflammatory and antifibrotic actions.
PMID- 25115800
TI - Hepcidin Suppresses Brain Iron Accumulation by Downregulating Iron Transport
Proteins in Iron-Overloaded Rats.
AB - Iron accumulates progressively in the brain with age, and iron-induced oxidative
stress has been considered as one of the initial causes for Alzheimer's disease
(AD) and Parkinson's disease (PD). Based on the role of hepcidin in peripheral
organs and its expression in the brain, we hypothesized that this peptide has a
role to reduce iron in the brain and hence has the potential to prevent or delay
brain iron accumulation in iron-associated neurodegenerative disorders. Here, we
investigated the effects of hepcidin expression adenovirus (ad-hepcidin) and
hepcidin peptide on brain iron contents, iron transport across the brain-blood
barrier, iron uptake and release, and also the expression of transferrin receptor
1 (TfR1), divalent metal transporter 1 (DMT1), and ferroportin 1 (Fpn1) in
cultured microvascular endothelial cells and neurons. We demonstrated that
hepcidin significantly reduced brain iron in iron-overloaded rats and suppressed
transport of transferrin-bound iron (Tf-Fe) from the periphery into the brain.
Also, the peptide significantly inhibited expression of TfR1, DMT1, and Fpn1 as
well as reduced Tf-Fe and non-transferrin-bound iron uptake and iron release in
cultured microvascular endothelial cells and neurons, while downregulation of
hepcidin with hepcidin siRNA retrovirus generated opposite results. We concluded
that, under iron-overload, hepcidin functions to reduce iron in the brain by
downregulating iron transport proteins. Upregulation of brain hepcidin by ad
hepcidin emerges as a new pharmacological treatment and prevention for iron
associated neurodegenerative disorders.
PMID- 25115803
TI - Unravelling the structure of electrocatalytically active Fe-N complexes in carbon
for the oxygen reduction reaction.
AB - Non-precious Fe/N co-modified carbon electrocatalysts have attracted great
attention due to their high activity and stability in oxygen reduction reaction
(ORR). Compared to iron-free N-doped carbon electrocatalysts, Fe/N-modified
electrocatalysts show four-electron selectivity with better activity in acid
electrolytes. This is believed relevant to the unique Fe-N complexes, however,
the Fe-N structure remains unknown. We used o,m,p-phenylenediamine as nitrogen
precursors to tailor the Fe-N structures in heterogeneous electrocatalysts which
contain FeS and Fe3 C phases. The electrocatalysts have been operated for 5000
cycles with a small 39 mV shift in half-wave potential. By combining advanced
electron microscopy and Mossbauer spectroscopy, we have identified the
electrocatalytically active Fe-N6 complexes (FeN6,
[Fe(III)(porphyrin)(pyridine)2]). We expect the understanding of the FeN6
structure will pave the way towards new advanced Fe-N based electrocatalysts.
PMID- 25115804
TI - Floating gate memory-based monolayer MoS2 transistor with metal nanocrystals
embedded in the gate dielectrics.
AB - Charge trapping layers are formed from different metallic nanocrystals in MoS2
based nanocrystal floating gate memory cells in a process compatible with
existing fabrication technologies. The memory cells with Au nanocrystals exhibit
impressive performance with a large memory window of 10 V, a high program/erase
ratio of approximately 10(5) and a long retention time of 10 years.
PMID- 25115802
TI - Role of far infra-red therapy in dialysis arterio-venous fistula maturation and
survival: systematic review and meta-analysis.
AB - INTRODUCTION: A well-functioning arteriovenous fistula (AVF) is the best modality
for vascular access in patients with end-stage renal disease (ESRD) requiring
haemodialysis (HD). However, AVFs' main disadvantage is the high rate of
maturation failure, with approximately one third (20%-50%) not maturing into
useful access. This review examine the use of Far-Infra Red therapy in an attempt
to enhance both primary (unassisted) and secondary (assisted) patency rates for
AVF in dialysis and pre-dialysis patients. METHOD: We performed an online search
for observational studies and randomised controlled trials (RCTs) that evaluated
FIR in patients with AVF. Eligible studies compared FIR with control treatment
and reported at least one outcome measure relating to access survival. Primary
patency and secondary patency rates were the main outcomes of interest. RESULTS:
Four RCTs (666 patients) were included. Unassisted patency assessed in 610
patients, and was significantly better among those who received FIR (228/311)
compared to (185/299) controls (pooled risk ratio of 1.23 [1.12-1.35], p =
0.00001). In addition, the two studies which reported secondary patency rates
showed significant difference in favour of FIR therapy--160/168 patients-
compared to 140/163 controls (pooled risk ratio of 1.11 [1.04-1.19], p = 0.003).
CONCLUSION: FIR therapy may positively influence the complex process of AVF
maturation improving both primary and secondary patency rates. However blinded
RCTs performed by investigators with no commercial ties to FIR therapy
technologies are needed.
PMID- 25115806
TI - Post-mating morphological changes in the spermatozoon and spermatophore wall of
the crayfish Astacus leptodactylus: insight into a non-motile spermatozoon.
AB - Morphology of the crayfish spermatozoon and of the spermatophore wall during
three stages of final maturation including freshly ejaculated, post-mating, and
after spermatozoa release was studied and compared. The crayfish spermatophore
consists of a sperm mass enveloped by a three layered spermatophore wall. After
mating, the thickness of the outer layer of the spermatophore is increased. The
matrix in the middle layer of the spermatophore becomes reticulated, and granules
inside this layer release their contents. Fibers in the inner layer degrade to
small particles. The spermatozoon capsule swells and the space between the
capsule and the spermatozoon appears. The area of the plasma membrane is
increased by wrinkling of the surface and alteration from a single to a
multilayered structure at the anterior part of the acrosome. The density of the
subacrosome zone increases in the vicinity of the main body of the acrosome. With
the onset of fertilization, the layers of the spermatophore are dissolved by
female glair gland secretions. The spermatozoon extracellular capsule, plasma
membrane, and membranous lamellae are eliminated, and bundles of filaments are
released from anterior part of the acrosome. The subacrosome zone loses electron
density and retracts. The electron-dense material of the innermost layer of the
acrosome is discharged and, together with acrosome filaments, forms a
filament/droplet structure at the anterior part of the spermatozoon. The most
important change is observed in the subacrosome zone, which may play a key role
in the fertilization. Also, morphological changes of the spermatozoon that occur
after release from the capsule, especially formation of the filament/droplet
structure, may contribute to the mechanism of egg-spermatozoon binding in the
crayfish, representative of animals with non-motile spermatozoa.
PMID- 25115805
TI - Depletion of regulatory T cells augments a vaccine-induced T effector cell
response against the liver-stage of malaria but fails to increase memory.
AB - Regulatory T cells (T(reg)) have been shown to restrict vaccine-induced T cell
responses in different experimental models. In these studies CD4(+)CD25(+) T(reg)
were depleted using monoclonal antibodies against CD25, which might also
interfere with CD25 on non-regulatory T cell populations and would have no effect
on Foxp3(+)CD25(-) T(reg). To obtain more insights in the specific function of
T(reg) during vaccination we used mice that are transgenic for a bacterial
artificial chromosome expressing a diphtheria toxin (DT) receptor-eGFP fusion
protein under the control of the foxp3 gene locus (depletion of regulatory T cell
mice; DEREG). As an experimental vaccine-carrier recombinant Bordetella adenylate
cyclase toxoid fused with a MHC-class I-restricted epitope of the
circumsporozoite protein (ACT-CSP) of Plasmodium berghei (Pb) was used. ACT-CSP
was shown by us previously to introduce the CD8+ epitope of Pb-CSP into the MHC
class I presentation pathway of professional antigen-presenting cells (APC).
Using this system we demonstrate here that the number of CSP-specific T cells
increases when T(reg) are depleted during prime but also during boost
immunization. Importantly, despite this increase of T effector cells no
difference in the number of antigen-specific memory cells was observed.
PMID- 25115807
TI - Effects of different levels of dietary selenium on the proliferation of
spermatogonial stem cells and antioxidant status in testis of roosters.
AB - The objective of this study was to investigate the different levels of dietary Se
(from sodium selenite) on the proliferation of SSCs (spermatogonial stem cells)
in testis of roosters. Also, the antioxidant status and Se content in blood
plasma and testis were evaluated. A total of eighty 12-week-old Hy-Line Variety
white roosters at an averaged body weight of 1.38 +/- 0.2 kg were selected and
randomly divided into four experimental groups. They were fed with the basal diet
(0.044 mgSe/kg DM) supplemented with 0 (control), 0.5, 1.0 or 2.0 mgSe/kg DM
(from sodium selenite). After the feeding experiment, blood and testis samples
were collected for analysis of the antioxidant status and Se concentration. The
testis samples were also used to examine the Thy-1 and beta1-integrin mRNA
expression by RT-PCR and detect the population of SSCs by immunofluorescence
analysis. The results show that Se concentration in blood and testis of the
animals was progressively increased with the increasing Se level in diet. The
highest GSH-Px (glutathione peroxidase) activity and lowest MDA content in blood
and testis was obtained in the treatment of 0.5mg/kg. RT-PCR analysis showed that
mRNA expression of SSCs markers were significantly lower in the control and
1.0mg/kg groups when compared with that in the treatment of 0.5mg/kg. A similar
trend was observed in the population of SSCs analyzed by immunofluorescence
assay. These data suggest that dietary Se can influence the population of SSCs of
roosters during spermatogenesis and that oxidative stress can modulate SSCs
behavior through regulating some key factors during spermatogenesis.
PMID- 25115808
TI - Outcome prediction by the transcript level of BCR-ABL at 3 months in patients
with chronic myeloid leukemia treated with imatinib--a single institution
historical experience.
AB - The BCR-ABL transcript level (<= 10%) at 3 months after tyrosine kinase
inhibitors can predict long term outcome in the patients with chronic myeloid
leukemia in chronic phase (CML-CP). However, the significance of transcript level
was still not determined in different risk groups of patients. A total of 299
patients with CML-CP were enrolled and stratified according to prior interferon
alpha (IFN) treatment, age, and interval time between diagnosis and imatinib
treatment to investigate the prediction value of BCR-ABL transcript level for
overall survival (OS), event-free survival (EFS), progression-free survival
(PFS). Univariate and multivariate analysis proved that BCR-ABL transcript level
at 3 months were associated with the treatment outcome. However, in the patients
with prior IFN treatment, younger age, and longer interval between diagnosis and
IM treatment, the predictive value of transcript value remain obscure in terms of
EFS, PFS and OS, respectively, as well as cumulative incidence of PCyR, CCR, MMR
and CMR. In conclusion, the transcript level of BCR-ABL at 3 months could serve
as a predictive parameter, but should be used with caution.
PMID- 25115810
TI - Solid organ transplant recipients: clinical considerations in the application of
exercise.
AB - Over 100 000 solid organ transplants are performed worldwide each year and this
has a significant impact on physical function and quality of life. However, the
capacity for exercise in solid-organ recipients is reduced. Regular physical
activity improves most of the indices of fitness in these patients but, with few
exceptions, they do not reach the values seen in healthy controls. The reason for
the 40-60% reduction in maximal exercise capacity is not clear; the disease
process, need for life long immunosuppression and sedentary lifestyle all
contribute. The interaction between exercise and immunosuppressing medication
merits research as does the specifics of the exercise prescription for these
patients. This paper reviews important features of this rapidly expanding group
of patients and suggests clinical considerations in the application of exercise
in this population.
PMID- 25115811
TI - Self-assembly of three-dimensional open structures using patchy colloidal
particles.
AB - Open structures can display a number of unusual properties, including a negative
Poisson's ratio, negative thermal expansion, and holographic elasticity, and have
many interesting applications in engineering. However, it is a grand challenge to
self-assemble open structures at the colloidal scale, where short-range
interactions and low coordination number can leave them mechanically unstable. In
this paper we discuss the self-assembly of three-dimensional open structures
using triblock Janus particles, which have two large attractive patches that can
form multiple bonds, separated by a band with purely hard-sphere repulsion. Such
surface patterning leads to open structures that are stabilized by orientational
entropy (in an order-by-disorder effect) and selected over close-packed
structures by vibrational entropy. For different patch sizes the particles can
form into either tetrahedral or octahedral structural motifs which then compose
open lattices, including the pyrochlore, the hexagonal tetrastack and the
perovskite lattices. Using an analytic theory, we examine the phase diagrams of
these possible open and close-packed structures for triblock Janus particles and
characterize the mechanical properties of these structures. Our theory leads to
rational designs of particles for the self-assembly of three-dimensional
colloidal structures that are possible using current experimental techniques.
PMID- 25115809
TI - Recollection and familiarity in aging individuals with mild cognitive impairment
and Alzheimer's disease: a literature review.
AB - Memory impairment is a central cognitive symptom in mild cognitive impairment
(MCI) and Alzheimer Disease (AD). Recognition tasks are often used to
characterize and define the nature of memory deficits. Dual-process theories
posit that familiarity and recollection are independently involved in the
recognition of previously encountered material and both contribute to successful
recognition. Recent evidence indicates that there is a double dissociation in the
neuronal substrates of those two processes. More precisely, it has been suggested
that perirhinal and entorhinal areas are selectively involved in familiarity
based recognition, while the hippocampus is associated with recollection.
Interestingly, these regions are among the first to be targeted by
neurofibrillary tangles, one of AD's neuropathological hallmarks. Impairment in
recognition performance can occur in the very early stages of AD, such as MCI. To
define the nature of recognition impairment in these clinical populations, we
reviewed the current literature on familiarity and recollection performance in
individuals with MCI and AD. Together with clinical features, methodological
factors are taken into consideration in the interpretation of findings.
PMID- 25115812
TI - SdrC induces staphylococcal biofilm formation through a homophilic interaction.
AB - The molecular pathogenesis of many Staphylococcus aureus infections involves
growth of bacteria as biofilm. In addition to polysaccharide intercellular
adhesin (PIA) and extracellular DNA, surface proteins appear to mediate the
transition of bacteria from planktonic growth to sessile lifestyle as well as
biofilm growth, and can enable these processes even in the absence of PIA
expression. However, the molecular mechanisms by which surface proteins
contribute to biofilm formation are incompletely understood. Here we demonstrate
that self-association of the serine-aspartate repeat protein SdrC promotes both
bacterial adherence to surfaces and biofilm formation. However, this homophilic
interaction is not required for the attachment of bacteria to abiotic surfaces.
We identified the subdomain that mediates SdrC dimerization and subsequent cell
cell interactions. In addition, we determined that two adjacently located amino
acid sequences within this subdomain are required for the SdrC homophilic
interaction. Comparative amino acid sequence analysis indicated that these
binding sites are conserved. In summary, our study identifies SdrC as a novel
molecular determinant in staphylococcal biofilm formation and describes the
mechanism responsible for intercellular interactions. Furthermore, these findings
contribute to a growing body of evidence suggesting that homophilic interactions
between surface proteins present on neighbouring bacteria induce biofilm growth.
PMID- 25115814
TI - Oligodendroglial response in the spinal cord in TDP-43 proteinopathy with motor
neuron involvement.
AB - BACKGROUND: TDP-43 proteinopathies represent a spectrum of neurodegenerative
disorders. Variable clinical presentations including frontotemporal dementia,
amyotrophic lateral sclerosis (ALS) and mixed forms are associated with the
spatial heterogeneity of the TDP-43 pathology. Recent studies have emphasized the
role of oligodendrocytes in the pathogenesis of ALS. OBJECTIVE: To evaluate
whether TDP-43 proteinopathies are associated with an oligodendroglial response.
METHODS: We performed a study on 7 controls and 10 diseased patients with spinal
cord involvement. Using the oligodendroglia-specific antibody TPPP/p25, we
assessed oligodendrocyte density in the lateral corticospinal tracts (LCSs) along
with the presence of perineuronal oligodendrocytes (PNOGs) in the anterior horns.
We performed a densitometry of myelin basic protein (MBP) immunoreactivity. The
numbers of TDP-43 and p62 immunoreactive inclusions were counted in both the LCSs
and the anterior horns. RESULTS: Double immunolabeling confirmed that
oligodendrocytes harbor TDP-43 inclusions. In the LCSs, MBP density, but not the
number of oligodendrocytes, was decreased in the diseased group. However,
oligodendrocyte counts in the LCS correlated positively, and the density of MBP
inversely, with the number of neuronal inclusions in the anterior horn,
suggestive of a compensatory response of oligodendrocytes. The number of neurons
with PNOGs correlated with the amount of inclusions. CONCLUSION: Our study
further emphasizes the importance of oligodendroglia in the pathogenesis of TDP
43 proteinopathies with spinal cord involvement.
PMID- 25115813
TI - The need for improved identification and accurate classification of stages 3-5
Chronic Kidney Disease in primary care: retrospective cohort study.
AB - BACKGROUND: Around ten percent of the population have been reported as having
Chronic Kidney Disease (CKD), which is associated with increased cardiovascular
mortality. Few previous studies have ascertained the chronicity of CKD. In the
UK, a payment for performance (P4P) initiative incentivizes CKD (stages 3-5)
recognition and management in primary care, but the impact of this has not been
assessed. METHODS AND FINDINGS: Using data from 426 primary care practices
(population 2,707,130), the age standardised prevalence of stages 3-5 CKD was
identified using two consecutive estimated Glomerular Filtration Rates (eGFRs)
seven days apart. Additionally the accuracy of practice CKD registers and the
relationship between accurate identification of CKD and the achievement of P4P
indicators was determined. Between 2005 and 2009, the prevalence of stages 3-5
CKD increased from 0.3% to 3.9%. In 2009, 30,440 patients (1.1% unadjusted)
fulfilled biochemical criteria for CKD but were not on a practice CKD register
(uncoded CKD) and 60,705 patients (2.2% unadjusted) were included on a practice
CKD register but did not fulfil biochemical criteria (miscoded CKD). For patients
with confirmed CKD, inclusion in a practice register was associated with
increasing age, male sex, diabetes, hypertension, cardiovascular disease and
increasing CKD stage (p<0.0001). Uncoded CKD patients compared to miscoded
patients were less likely to achieve performance indicators for blood pressure
(OR 0.84, 95% CI 0.82-0.86 p<0.001) or recorded albumin-creatinine ratio (OR
0.73, 0.70-0.76, p<0.001). CONCLUSIONS: The prevalence of stages 3-5 CKD, using
two laboratory reported eGFRs, was lower than estimates from previous studies.
Clinically significant discrepancies were identified between biochemically
defined CKD and appearance on practice registers, with misclassification
associated with sub-optimal care for some people with CKD.
PMID- 25115816
TI - Biomechanical considerations of foot-ground contact in T'ai Chi Chuan.
AB - Although numerous studies have linked t'ai chi chuan (TCC) practice with benefits
for balance, reduction in the number of falls, and in the fear of falling, most
of them did not address the causes of these benefits in depth. Some studies,
however, sought to determine the causes from the biomechanical point of view.
This article aims to thoroughly describe and critically review recent papers on
foot-ground contact in TCC practice, one of the parameters involved in balance
biomechanics in TCC performance. No previous review on this subject has been
found. Nine electronic databases were searched for publications between 1996 and
2013. Studies were excluded if they were not published in English or were
abstracts, posters, or summaries from conferences. From a total of 195 articles
identified, 4 randomized controlled trials and 3 non-randomized controlled trials
were eligible for the analysis. The number of studies that assessed foot-ground
contact in TCC and effects on normal gait, postural control improvement, and fall
prevention is still quite small. These studies were based on intervention
protocols and used populations that were too heterogeneous to allow reliable
comparisons. According to the studies analyzed, TCC practice clearly improved
parameters associated with foot-ground contact. Nevertheless, the manner in which
these benefits are transferred to daily displacement habits still remains
unclear.
PMID- 25115818
TI - Taming molecular collisions using electric and magnetic fields.
AB - The motion of molecules that possess a permanent electric or magnetic dipole
moment can be manipulated using electric or magnetic fields. Various devices have
been developed over the last few decades to deflect or focus molecules, to orient
them in space, and to decelerate or accelerate them. These precisely controlled
molecules are ideal starting points for scattering experiments that reveal the
quantum mechanical nature of molecular interactions. In this Tutorial Review, we
present an overview of the various manipulation tools, discuss how they can be
used to advantage in molecular beam scattering experiments, and review recent
progress in this field. We describe a selection of benchmark experiments that
illustrate the unique possibilities that are available nowadays to study
molecular collisions under controlled conditions.
PMID- 25115815
TI - Identification and characterization of Dicer1e, a Dicer1 protein variant, in oral
cancer cells.
AB - BACKGROUND: The human dicer1 gene has been predicted to produce several mRNA
variants that encode truncated Dicer1 proteins of varying lengths. One of these
Dicer1 variants, Dicer1e, was recently found to be differentially expressed in
breast cancer cells. Because the expression and function of the Dicer1e protein
variant has not been well characterized and the underlying molecular mechanisms
for the development of oral squamous cell carcinomas (OSCCs) are poorly
understood, the present study sought to characterize the biological role of
Dicer1e and determine its relationship, if any, to OSCC pathogenesis. METHODS:
Western blot analyses were used to examine Dicer1e expression levels in a panel
of oral cancer cells/tissues and during epithelial-mesenchymal transition (EMT),
followed by 5'/3'-RACE analyses to obtain the full-length Dicer1e transcript.
Biochemical fractionation and indirect immunofluorescent studies were performed
to determine the cellular localization of Dicer1e and the effects of Dicer1e
silencing on cancer cell proliferation, clonogenicity, and drug sensitivity were
also assessed. RESULTS: Dicer1e protein levels were found to be overexpressed in
OSCC cell lines of epithelial phenotype and in OSCC tissues with its levels
downregulated during EMT. Moreover, the Dicer1e protein was observed to
predominantly localize in the nucleus. 5'/3'-RACE analyses confirmed the presence
of the Dicer1e transcript and silencing of Dicer1e impaired both cancer cell
proliferation and clonogenicity by inducing either apoptosis and/or G2/M cell
cycle arrest. Lastly, Dicer1e knockdown enhanced the chemosensitivity of oral
cancer cells to cisplatin. CONCLUSION: The expression levels of Dicer1e influence
the pathogenesis of oral cancer cells and alter their response to
chemosensitivity, thus supporting the importance of Dicer1e as a therapeutic
target for OSCCs.
PMID- 25115817
TI - Corner store purchases made by adults, adolescents and children: items,
nutritional characteristics and amount spent.
AB - OBJECTIVE: Corner stores, also known as bodegas, are prevalent in low-income
urban areas and primarily stock high-energy foods and beverages. Little is known
about individual-level purchases in these locations. The purpose of the present
study was to assess corner store purchases (items, nutritional characteristics
and amount spent) made by children, adolescents and adults in a low-income urban
environment. DESIGN: Evaluation staff used 9238 intercept surveys to directly
examine food and beverage purchases. SETTING: Intercepts were collected at 192
corner stores in Philadelphia, PA, USA. SUBJECTS: Participants were adult,
adolescent and child corner store shoppers. RESULTS: Among the 9238 intercept
surveys, there were 20 244 items. On average, at each corner store visit,
consumers purchased 2.2 (sd 2.1) items (1.3 (sd 2.0) foods and 0.9 (sd 0.9)
beverages) that cost $US 2.74 (sd $US 3.52) and contained 2786.5 (sd 4454.2) kJ
(666.0 (sd 1064.6) kcal). Whether the data were examined as a percentage of total
items purchased or as a percentage of intercepts, the most common corner store
purchases were beverages, chips, prepared food items, pastries and candy.
Beverage purchases occurred during 65.9% of intercepts and accounted for 39.2% of
all items. Regular soda was the most popular beverage purchase. Corner store
purchases averaged 66.2 g of sugar, 921.1 mg of sodium and 2.5 g of fibre per
intercept. Compared with children and adolescents, adults spent the most money
and purchased the most energy. CONCLUSIONS: Urban corner store shoppers spent
almost $US 3.00 for over 2700 kJ (650 kcal) per store visit. Obesity prevention
efforts may benefit from including interventions aimed at changing corner store
food environments in low-income, urban areas.
PMID- 25115819
TI - The effect of tooth loss on gait stability of community-dwelling older adults.
AB - OBJECTIVE: To investigate the effects of tooth loss on gait stability in a
healthy elderly population. METHODS: A case-control study was conducted among
healthy and prosthetically well-restored seniors over the age of 65 years. The
test group comprised 24 edentulous participants who were restored with complete
dentures in the upper jaw and an overdenture fixed on two implants in the lower
jaw. The control group comprised 25 dentate participants who either still had
their natural teeth or were restored with conventional fixed partial dentures.
Gait stability was evaluated by measuring the parameters 'gait velocity' and
'cycle-time variability' during self-selected normal walking speed and under dual
task performance conditions. Measurements were conducted using the GAITRite((r))
electronic walkway system. RESULTS: Dentated and fixed restored participants (the
control group) had a significantly higher gait velocity compared with denture
wearers (the test group) under both normal walking (p = 0.03) and dual-task
performance conditions (p = 0.01). In each test condition, among edentulous
participants, gait velocity did not significantly differ according to whether the
participant wore their dentures. CONCLUSION: The present results suggest that
tooth loss in healthy seniors is associated with lower gait velocity and
therefore may have a negative impact on gait stability.
PMID- 25115820
TI - Epilepsy surgery in children: why, when and how?
AB - Epilepsy surgery is safe and effective treatment in children who fail to respond
to antiepileptic medications. After failure of two appropriate antiepileptic
medications, chances that the child will become seizure free with more or
different medications is <5%, and she should be diagnosed with "refractory
epilepsy". A consideration for surgical candidacy should be given to all children
who fulfill the definition of refractory epilepsy. In appropriately selected
children, epilepsy surgery offers a high chance of seizure freedom without
incurring any new post-operative neurological deficits. No age is bar to epilepsy
surgery. Even infants can safely have epilepsy surgery if they are surgical
candidates. For most children, who are surgical candidates, a good history and
physical examination, video EEG evaluation, and a high quality brain MRI are
sufficient to make surgical decision. These tools are increasingly available all
over the world. Better education of families, Pediatricians, Pediatric
Neurologists and community care-givers is necessary to salvage children early
from mortality and morbidity of untreated, sometimes life long, epilepsy.
PMID- 25115824
TI - Direct synthesis of chromium perovskite oxyhydride with a high magnetic
transition temperature.
AB - We report a novel oxyhydride SrCrO2H directly synthesized by a high-pressure high
temperature method. Powder neutron and synchrotron X-ray diffraction revealed
that this compound adopts the ideal cubic perovskite structure (Pm3m) with O(2
)/H(-) disorder. Surprisingly, despite the non-bonding nature between Cr 3d t(2g)
orbitals and the H 1s orbital, it exhibits G-type spin ordering at T(N)~380 K,
which is higher than that of RCrO3 (R=rare earth) and any chromium oxides. The
enhanced T(N) in SrCrO2H with four Cr-O-Cr bonds in comparison with RCr(3+)O3
with six Cr-O-Cr bonds is reasonably explained by the tolerance factor. The
present result offers an effective strategy to tune octahedral tilting in
perovskites and to improve physical and chemical properties through mixed anion
chemistry.
PMID- 25115823
TI - Role of peripheral purinoceptors in the development of bee venom-induced
nociception: a behavioural and electrophysiological study in rats.
AB - Colocalization of purinergic P2X and P2Y receptors in dorsal root ganglion
sensory neurons implies that these receptors play an integrative role in the
nociceptive transmission process under inflammatory conditions. In the present
study, behavioural and in vivo electrophysiological methods were used to examine
the peripheral role of P2 receptors in the persistent nociceptive responses
induced by subcutaneous bee venom injection (2 mg/mL) in. Sprague-Dawley rats
Local pretreatment with the wide-spectrum P2 receptor antagonist
pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 1 mmol/L, 50 MUL)
10 min prior to s.c. bee venom injection significantly suppressed the duration of
spontaneous nociceptive lifting/licking behaviour, inhibited mechanical
hyperalgesia and decreased the firing of spinal dorsal horn wide dynamic range
neurons in response to bee venom, without affecting primary thermal and mirror
image hyperalgesia. The localized antinociceptive action of PPADS was not due to
a systemic effect, because application of the same dose of PPADS to the
contralateral side was not effective. The results suggest that activation of
peripheral P2 receptors is involved in the induction of nociceptive responses,
mechanical hyperalgesia and the excitation of sensory spinal neurons.
PMID- 25115825
TI - Facet-dependent surface plasmon resonance properties of Au-Cu2 o core-shell
nanocubes, octahedra, and rhombic dodecahedra.
AB - Au-Cu2 O core-shell nanocubes, octahedra, and rhombic dodecahedra display facet
dependent optical properties. Furthermore, different-sized Au-Cu2 O octahedra
with 58, 65, 68, and 73 nm octahedral gold cores clearly show a transition from
the shell thickness-independent gold surface plasmon resonance band for octahedra
with smaller gold cores to progressive red-shifts of the band with increasing
shell thickness in octahedra with larger gold cores.
PMID- 25115821
TI - Brain Circuitry Supporting Multi-Organ Autonomic Outflow in Response to Nausea.
AB - While autonomic outflow is an important co-factor of nausea physiology, central
control of this outflow is poorly understood. We evaluated sympathetic (skin
conductance level) and cardiovagal (high-frequency heart rate variability)
modulation, collected synchronously with functional MRI (fMRI) data during
nauseogenic visual stimulation aimed to induce vection in susceptible
individuals. Autonomic data guided analysis of neuroimaging data, using a
stimulus-based (analysis windows set by visual stimulation protocol) and percept
based (windows set by subjects' ratings) approach. Increased sympathetic and
decreased parasympathetic modulation was associated with robust and anti
correlated brain activity in response to nausea. Specifically, greater autonomic
response was associated with reduced fMRI signal in brain regions such as the
insula, suggesting an inhibitory relationship with premotor brainstem nuclei.
Interestingly, some sympathetic/parasympathetic specificity was noted. Activity
in default mode network and visual motion areas was anti-correlated with
parasympathetic outflow at peak nausea. In contrast, lateral prefrontal cortical
activity was anti-correlated with sympathetic outflow during recovery, soon after
cessation of nauseogenic stimulation. These results suggest divergent central
autonomic control for sympathetic and parasympathetic response to nausea.
Autonomic outflow and the central autonomic network underlying ANS response to
nausea may be an important determinant of overall nausea intensity and,
ultimately, a potential therapeutic target.
PMID- 25115826
TI - Association of bone mineral density with postural stability and the fear of
falling in Spanish postmenopausal women.
AB - OBJECTIVE: The purpose of our study was to investigate the relationship between
bone mineral density (BMD) and postural stability and the fear of falling in a 50
to 65-year-old postmenopausal population. STUDY DESIGN: A cross-sectional,
observational study was conducted on 118 postmenopausal women. According to their
BMD values, participants were divided into two groups: BMD>-2.0SD (n=95) and <=
2.0SD (n=23). MAIN OUTCOME MEASURES: Postural stability, assessed with a
resistive multi-sensor platform, fear of falling (FoF) and the history of falls
in the last 12 months were investigated. RESULTS: Women with BMD<=-2.0SD reported
a significantly increased FoF when compared to women with BMD>-2.0SD (P=0.024,
eta(2)=0.045, 1-beta=0.624). In the postural stability analysis, the group with
BMD<=-2.0SD showed, under the eyes-open condition, statistically significantly
higher values for the velocity (VEO) (P=0.040, eta(2)=0.037, 1-beta=0.539) and
the anteroposterior mean displacement of the center of pressure (YEO; P=0.017,
eta(2)=0.049, 1-beta=0.669). No significant differences between groups were
observed in the history of falls or in the rest of the stabilometric analyses.
CONCLUSIONS: In Spanish postmenopausal women under 65 years, a BMD<=-2.0SD is
significantly associated with postural instability (elevated VEO and XEO) and an
increased FoF, which are two highly influential factors in the risk of falling.
PMID- 25115828
TI - Predicting drug substances autoxidation.
AB - PURPOSE: Chemical degradation and stability in formulation is a recurrent issue
in pharmaceutical development of drugs. The objective of the present study was to
develop an in silico risk assessment of active pharmaceutical ingredients (APIs)
stability with respect to autoxidation. METHODS: The chemical degradation by
autoxidation of a diverse series of APIs has been investigated with molecular
modelling tools. A set of 45 organic compounds was used to test and validate the
various computational settings. Aiming to devise a methodology that could
reliably perform a risk assessment for potential sensibility to autoxidation,
different types of APIs, known for their autoxidation history were inspected. To
define the level of approximation needed, various density functional theory (DFT)
functionals and settings were employed and their accuracy and speed were
compared. RESULTS: The Local Density Approximation (LDA) gave the fastest results
but with a substantial deviation (systematic over-estimation) to known
experimental values. The Perdew-Burke-Ernzerhof (PBE) settings appeared to be a
good compromise between speed and accuracy. CONCLUSIONS: The present methodology
can now be confidently deployed in pharmaceutical development for systematic risk
assessment of drug stability.
PMID- 25115827
TI - In vitro and in vivo biological evaluation of O-carboxymethyl chitosan
encapsulated metformin nanoparticles for pancreatic cancer therapy.
AB - PURPOSE: In vitro anticancer effect and in vivo biodistribution and
biocompatibility of metformin encapsulated O-Carboxymethyl chitosan nanoparticles
were evaluated for its application as pancreatic cancer therapy. METHODS: In
vitro studies such as cell migration assay, clonogenic assay, cell cycle analysis
and qRT-PCR analysis were done in pancreatic cancer cells (MiaPaCa-2) treated
with O-CMC-metformin NPs for evaluating its anticancer potential. In vivo
biodistribution studies were carried out by NIR imaging of O-CMC-metformin NPs
after tagging it with ICG. In vivo biocompatibility of the NPs was assessed by
histopathology analysis of organs from mice administered with the NPs. RESULTS:
In vitro cell migration assay showed marginal effect of NPs on migration property
of pancreatic cancer cells (MiaPaCa-2). In vitro clonogenic assay established
that the O-CMC-metformin NPs reduced colony formation ability of the cancer
cells. While cell cycle analysis showed that the O-CMC-metformin NPs had only
minor effect on progression of cell cycle in the cancer cells. qRT-PCR analysis
exhibited reduced mRNA expression of p21, vanin 1 and MMP9 in pancreatic cancer
cells treated with the nanoparticles. In vivo NIR imaging study showed normal
biodistribution pattern of the intravenously injected O-CMC-metformin NPs
suggesting normal clearance rate of nanoparticles and no adverse toxicity to the
organs. CONCLUSIONS: The biocompatible O-CMC-metformin NPs with anticancer
potential and capability for normal biodistribution can be beneficial for the
treatment of pancreatic cancer.
PMID- 25115829
TI - Bisoprolol and bisoprolol-valsartan compatibility studied by differential
scanning calorimetry, nuclear magnetic resonance and X-ray powder diffractometry.
AB - PURPOSE: The objective of this study was to evaluate the thermal behavior of
crystalline and amorphous bisoprolol fumarate and its compatibility with
amorphous valsartan. This pharmacologically relevant drug combination is a
potential candidate for fixed-dose combination formulation. METHODS: DSC and
TMDSC were used to examine thermal behavior of bisoprolol fumarate. SSNMR and
XRPD were applied to probe the solid state forms. The thermal behavior of
physical mixtures with different concentrations of bisoprolol and valsartan were
examined by DSC and TMDSC, and the observed interactions were investigated by
XRPD, solution- and solid-state NMR. RESULTS: The phase transitions from thermal
methods and solid-state NMR spectra of crystalline and amorphous bisoprolol
fumarate are reported. Strong interactions between bisoprolol fumarate and
valsartan were observed above 60 C, resulting in the formation of a new amorphous
material. Solution- and solid-state NMR provided insight into the molecular
nature of the incompatibility. CONCLUSIONS: A combined analysis of thermal
methods, solution- and solid-state NMR and XRPD experiments allowed the
investigation of the conformational and dynamic properties of bisoprolol
fumarate. Since bisoprolol fumarate and valsartan react to form a new amorphous
product, formulation of a fixed-dose combination would require separate
reservoirs for bisoprolol and valsartan to prevent interactions. Similar problems
might be expected with other excipients or APIs containing carboxylic groups.
PMID- 25115830
TI - Human exposure to early morning Anopheles funestus biting behavior and personal
protection provided by long-lasting insecticidal nets.
AB - A shift towards early morning biting behavior of the major malaria vector
Anopheles funestus have been observed in two villages in south Benin following
distribution of long-lasting insecticidal nets (LLINs), but the impact of these
changes on the personal protection efficacy of LLINs was not evaluated. Data from
human and An. funestus behavioral surveys were used to measure the human exposure
to An. funestus bites through previously described mathematical models. We
estimated the personal protection efficacy provided by LLINs and the proportions
of exposure to bite occurring indoors and/or in the early morning. Average
personal protection provided by using of LLIN was high (>=80% of the total
exposure to bite), but for LLIN users, a large part of remaining exposure
occurred outdoors (45.1% in Tokoli-V and 68.7% in Lokohoue) and/or in the early
morning (38.5% in Tokoli-V and 69.4% in Lokohoue). This study highlights the
crucial role of LLIN use and the possible need to develop new vector control
strategies targeting malaria vectors with outdoor and early morning biting
behavior. This multidisciplinary approach that supplements entomology with social
science and mathematical modeling illustrates just how important it is to assess
where and when humans are actually exposed to malaria vectors before vector
control program managers, policy-makers and funders conclude what entomological
observations imply.
PMID- 25115832
TI - Investigation into the effect of hepatitis B virus on apoliprotein A1 expression
and its mechanism.
AB - BACKGROUND: Hepatitis B virus (HBV) infection poses a serious threat to human
health, with China being one of the highly affected countries. However, the
pathogenesis of chronic hepatitis B (CHB) is still unclear. Apolipoprotein A1
(ApoA1) which represents the major protein component of high-density lipoprotein
is normally secreted by hepatocytes. When hepatocytes are infected with HBV may
lead to the disruption of ApoA1 secretion. In this study, we investigated the
effect of HBV on ApoA1 expression and preliminarily explored its molecular
mechanism of regulation for revealing the pathogenesis of CHB. METHODS: The
expression of mRNA and protein of ApoA1 in Human HepG2 hepatoblastoma cells and
subline HepG2.2.15 cells were performed by reverse transcription-polymerase chain
reaction (RT-PCR) and Western-blot. The serum ApoA1, by the immune turbidimetric
test, and high-density lipoprotein cholesterol (HDL-C) in CHB patients and
healthy controls, based on the enzymatic method, were measured with
autobiochemical analyzer. The statistical difference was analyzed by SPSS 13.0.
HBV infectious clone, pHBV1.3, and ApoA1 gene promoter were co-transfected into
HepG2, and the luciferase activity was determined. The changes of ApoA1 mRNA and
protein expression were detected by RT-PCR and Western-blot method, after HepG2
cells were transfected with pHBV1.3. RESULTS: The expression of ApoA1 mRNA and
protein in HepG2.2.15 were lower than those in HepG2, and when compared with
healthy controls, serum levels of ApoA1 and HDL-C in CHB patients were lower (P <
0.05). pHBV1.3 in HepG2 cells restrained the activity of ApoA1 promoter, mRNA and
protein expression. CONCLUSIONS: HBV could inhibit the expression of ApoA1 in
vitro and in vivo.
PMID- 25115831
TI - Unique aspects of impulsive traits in substance use and overeating: specific
contributions of common assessments of impulsivity.
AB - Abstract Background: Impulsivity is a complex trait often studied in substance
abuse and overeating disorders, but the exact nature of impulsivity traits and
their contribution to these disorders are still debated. Thus, understanding how
to measure impulsivity is essential for comprehending addictive behaviors.
OBJECTIVES: Identify unique impulsivity traits specific to substance use and
overeating. METHODS: Impulsive Sensation Seeking (ImpSS) and Barratt's
Impulsivity scales (BIS) Scales were analyzed with a non-parametric factor
analytic technique (discriminant correspondence analysis) to identify group
specific traits on 297 individuals from five groups: Marijuana (n = 88), Nicotine
(n = 82), Overeaters (n = 27), Marijuauna + Nicotine (n = 63), and CONTROLs (n =
37). RESULTS: A significant overall factor structure revealed three components of
impulsivity that explained respectively 50.19% (pperm < 0.0005), 24.18% (pperm <
0.0005), and 15.98% (pperm < 0.0005) of the variance. All groups were
significantly different from one another. When analyzed together, the BIS and
ImpSS produce a multi-factorial structure that identified the impulsivity traits
specific to these groups. The group specific traits are (1) CONTROL: low impulse,
avoids thrill-seeking behaviors; (2) Marijuana: seeks mild sensation, is focused
and attentive; (3) Marijuana + Nicotine: pursues thrill-seeking, lacks focus and
attention; (4) Nicotine: lacks focus and planning; (5) Overeating: lacks focus,
but plans (short and long term). CONCLUSIONS: Our results reveal impulsivity
traits specific to each group. This may provide better criteria to define
spectrums and trajectories - instead of categories - of symptoms for substance
use and eating disorders. Defining symptomatic spectrums could be an important
step forward in diagnostic strategies.
PMID- 25115833
TI - Pirfenidone in idiopathic pulmonary fibrosis: real-life experience from a German
tertiary referral center for interstitial lung diseases.
AB - BACKGROUND: Pirfenidone is a novel antifibrotic drug for the treatment of mild-to
moderate idiopathic pulmonary fibrosis (IPF). However, adverse events may offset
treatment benefits and compliance. OBJECTIVES: To assess recent course of
disease, adverse events and compliance in patients who started pirfenidone.
METHODS: In an observational cohort study, 63 patients with mild-to-moderate IPF
who started pirfenidone between May 2011 and June 2013 were reviewed. Pulmonary
function, adverse events and treatment compliance were recorded at each clinic
visit. Disease progression was defined as a reduction of vital capacity >=10%
and/or diffusion capacity (DLCO) >=15%. RESULTS: Follow-up time on pirfenidone
treatment was 11 (+/-7) months. Sixty-six percent of the patients continued with
pirfenidone monotherapy and 34% of the patients received pirfenidone combined
with corticosteroids (CCS) and/or N-acetylcysteine (NAC). There was a
nonsignificant reduction in mean decline of percent predicted forced vital
capacity after treatment start (0.7 +/- 10.9%) compared to the pretreatment
period (6.6 +/- 6.7%, p = 0.098). Sixty-two percent of the patients had stable
disease on pirfenidone treatment. Adverse events affected 85% of the patients,
leading to discontinuation of pirfenidone in 20%. Adverse events and treatment
discontinuation were seen more frequently in patients with concomitant CCS and/or
NAC treatment. CONCLUSIONS: Adverse events affect the majority of patients
treated with pirfenidone, but are mostly manageable with supportive measures. In
this heterogeneous patient group, a nonsignificant effect of pirfenidone
treatment on pulmonary function was seen, underlining the need for more data on
patient selection criteria and efficacy of pirfenidone, particularly in patients
with coexistent emphysema and concomitant NAC/CCS treatment.
PMID- 25115834
TI - Severe oral infection due to Lactobacillus rhamnosus during induction
chemotherapy for acute myeloid leukemia.
AB - We report a case of severe oral infection with a high fever due to Lactobacillus
rhamnosus during induction chemotherapy for acute myeloid leukemia. The patient
did not improve on treatment with meropenem, clindamycin, or vancomycin until
neutrophil recovery. Since L. rhamnosus GG is used in dairy products, and the
patient ingested dairy products daily before starting chemotherapy, we suspected
an association between the ingestion of dairy products and the development of
infection. Pulsed-field gel electrophoresis using two different restriction
enzymes showed that the strain isolated from the patient was identical to the L.
rhamnosus GG strain isolated from dairy products and ATCC #53103. This was
confirmed by a PCR assay with species-specific L. rhamnosus GG primers. Since
Lactobacillus infection, particularly L. rhamnosus infection, can be fatal in
immunocompromised hosts, we should consider Lactobacillus as a causative organism
when Gram-positive rods are detected during treatment with broad-spectrum
antibiotics and vancomycin. The causal association between the ingestion of dairy
products containing Lactobacillus and Lactobacillus infection in
immunocompromised hosts warrants further study.
PMID- 25115835
TI - One-pot enzymatic synthesis of merochlorin A and B.
AB - The polycycles merochlorin A and B are complex halogenated meroterpenoid natural
products with significant antibacterial activities and are produced by the marine
bacterium Streptomyces sp. strain CNH-189. Heterologously produced enzymes and
chemical synthesis are employed herein to fully reconstitute the merochlorin
biosynthesis in vitro. The interplay of a dedicated type III polyketide synthase,
a prenyl diphosphate synthase, and an aromatic prenyltransferase allow formation
of a highly unusual aromatic polyketide-terpene hybrid intermediate which
features an unprecedented branched sesquiterpene moiety from isosesquilavandulyl
diphosphate. As supported by in vivo experiments, this precursor is furthermore
chlorinated and cyclized to merochlorin A and isomeric merochlorin B by a single
vanadium-dependent haloperoxidase, thus completing the remarkably efficient
pathway.
PMID- 25115837
TI - Automated formation of lipid membrane microarrays for ionic single-molecule
sensing with protein nanopores.
AB - Efficient use of membrane protein nanopores in ionic single-molecule sensing
requires technology for the reliable formation of suspended molecular membranes
densely arrayed in formats that allow high-resolution electrical recording. Here,
automated formation of bimolecular lipid layers is shown using a simple process
where a poly(tetrafluoroethylene)-coated magnetic bar is remotely actuated to
perform a turning motion, thereby spreading phospholipid in organic solvent on a
nonpolar surface containing a <1 mm(2) 4 * 4 array of apertures with embedded
microelectrodes (microelectrode cavity array). Parallel and high-resolution
single-molecule detection by single nanopores is demonstrated on the resulting
bilayer arrays, which are shown to form by a classical but very rapid self
assembly process. The technique provides a robust and scalable solution for the
problem of reliable, automated formation of multiple independent lipid bilayers
in a dense microarray format, while preserving the favorable electrical
properties of the microelectrode cavity array.
PMID- 25115836
TI - A prospective study of gynecological cancer risk in relation to adiposity
factors: cumulative incidence and association with plasma adipokine levels.
AB - BACKGROUND: Associations of obesity and obesity-related metabolic factors
(adiposity factors) with uterine corpus cancer (UCC) and ovarian cancer (OVC)
risk have been described. Still, a cause-effect relationship and the underlying
mediators remain unclear, particularly for low-incidence populations. We aimed to
prospectively determine whether adiposity factors could predict the development
of UCC and OVC in Taiwanese women. To explore the biological mediators linking
adiposity factors to cancer risk, we examined the association of two adipokines,
leptin and adiponectin, with the gynecological cancers. METHODS: Totally, 11,258
women, aged 30-65, were recruited into the Community-Based Cancer Screening
Program (CBCSP) study during 1991-1993, and were followed for UCC and OVC cases
until December 31, 2011. Cox proportional hazard models were used to estimate
hazard ratios (HRs). Adiposity factors and risk covariates were assessed at
recruitment. Newly-developed cancer cases were determined from data in the
government's National Cancer Registry and Death Certification System. For
adipokienes study, a nested case-control study was conducted within the cohort.
Baseline plasma samples of 40 incident gynecological cancer cases and 240 age
menopause-matched controls were assayed for adipokines levels. FINDINGS: There
were 38 and 30 incident cases of UCC and OVC, respectively, diagnosed during a
median 19.9 years of follow-up. Multivariate analysis showed that alcohol intake
(HR = 16.00, 95% = 4.83-53.00), high triglyceride levels (HR = 2.58, 95% = 1.28
5.17), and years of endogenous estrogen exposure per 5-year increment (HR = 1.91,
95% = 1.08-3.38) were associated with increased UCC risk. High body mass index
(BMI >= 27 kg/m(2), HR = 2.90, 95% = 1.30-6.46) was associated with increased
OVC risk. Analysis further showed an independent effect of adipokines on UCC and
OVC risk after adjustment of the risk covariates. CONCLUSION: We provided
evidence that alcohol intake, high triglyceride levels and long endogenous
estrogen exposure increase UCC risk, whereas obesity positively predicts OVC
risk. Circulating adipokines may mediate the link of adiposity factors to
gynecological cancer risk.
PMID- 25115838
TI - Modulation of platelet activation and thrombus formation using a pan-PI3K
inhibitor S14161.
AB - The phosphatidylinositol 3-kinase (PI3K) signaling pathway is critical in
modulating platelet functions. In the present study, we evaluated the effect of
S14161, a recently identified pan-class I PI3K inhibitor, on platelet activation
and thrombus formation. Results showed that S14161 inhibited human platelet
aggregation induced by collagen, thrombin, U46619, and ADP in a dose-dependent
manner. Flow cytometric studies showed that S14161 inhibited convulxin- or
thrombin-induced P-selectin expression and fibrinogen binding of single platelet.
S14161 also inhibited platelet spreading on fibrinogen and clot retraction,
processes mediated by outside-in signaling. Using a microfluidic chamber we
demonstrated that S14161 decreased platelet adhesion on collagen-coated surface
by about 80%. Western blot showed that S14161 inhibited phosphorylation of Akt at
both Ser473 and Thr308 sites, and GSK3beta at Ser9 in response to collagen,
thrombin, or U46619. Comparable studies showed that S14161 has a higher potential
bioavailability than LY294002, a prototypical inhibitor of pan-class I PI3K.
Finally, the effects of S14161 on thrombus formation in vivo were measured using
a ferric chloride-induced carotid artery injury model in mice. The
intraperitoneal injection of S14161 (2 mg/kg) to male C57BL/6 mice significantly
extended the first occlusion time (5.05 +/- 0.99 min, n = 9) compared to the
vehicle controls (3.72 +/- 0.95 min, n = 8) (P<0.05), but did not prolong the
bleeding time (P>0.05). Taken together, our data showed that S14161 inhibits
platelet activation and thrombus formation without significant bleeding tendency
and toxicity, and considering its potential higher bioavailability, it may be
developed as a novel therapeutic agent for the prevention of thrombotic
disorders.
PMID- 25115839
TI - Thrombophilic factor analysis in cirrhotic patients with portal vein thrombosis.
AB - Liver cirrhosis, myeloproliferative disorders (MPDs) and prothrombotic mutations
are aetiologic factors for portal vein thrombosis (PVT). The role and frequency
of thrombophilic genetic risk factors in cirrhotic patients is not well
established. In this case-control study, we investigated the frequency of Janus
kinase 2 (JAK2) (JAK2 V617F), Factor V Leiden (FVL G1691A), and Prothrombin
(G20210A) mutations in cirrhotic patients with PVT (LCi+/PVT+ group, n = 21) in
comparison with two control collectives (cirrhotic patients without PVT, LCi+/PVT
group, n = 43; PVT patients without liver cirrhosis, LCi-/PVT+ group, n = 29).
In the LCi+/PVT+ group, JAK2 V617F was present in 2/21 patients (10 %; p = 0.104
compared to LCi+/PVT-; p = 0.092 compared to LCi-/PVT+), whereas 0/43 LCi+/PVT-
patients (0 %; p < 0.001 compared to LCi-/PVT+) and 9/29 LCi-/PVT+ patients (31
%) harboured this mutation. The FVL G1691A mutation was identified in 1/21
patients (5 %) in the LCi+/PVT+ group, in 5/43 patients (12 %) in the LCi+/PVT-
group, and in 2/29 patients (7 %) in the LCi-/PVT+ group. The Prothrombin G20210A
mutation was present in 0/21 LCi+/PVT+ patients (0 %), in 1/43 LCi+/PVT- patients
(2 %), and in 4/29 patients (14 %) in the LCi-/PVT+ group. This study provides
evidence that a relevant proportion of cirrhotic patients with PVT harbours a
JAK2 V617F mutation.
PMID- 25115842
TI - Obesity, abdominal obesity and migraine: a cross-sectional analysis of ELSA
Brasil baseline data.
AB - BACKGROUND AND AIM: Most studies assessing the association between migraine and
obesity have shown conflicting results. We aimed to evaluate the association
between obesity and migraine in ELSA-Brasil, a cohort study of 15,105 individuals
aged 35-74 years. METHODS: We assessed migraine using a validated questionnaire
based on International Headache Society criteria and anthropometric measurements
using standard techniques. Migraine was categorized as daily and non-daily. World
Health Organization criteria were used to categorize overweight, obesity and
abdominal obesity (AbO). We performed a cross-sectional analysis using
multivariate logistic regression models to study the association between migraine
and obesity (body mass index (BMI) >= 30 kg/m(2)), compared to controls without
migraine. RESULTS: We found an association between daily migraine and obesity
(odds ratio (OR) 1.86; 95% confidence interval (95% CI): 1.12-3.09). Although the
presence of AbO was not associated with migraine, interaction models showed that
the association between obesity and daily migraine remained strong only in the
absence of AbO diagnosis, notably in individuals aged 35-49 years. DISCUSSION: In
our large sample of individuals aged 35 years or older, obesity, but not AbO, was
associated with daily migraine. AbO influenced the association between BMI and
daily migraine in migraineurs aged 35-49 years.
PMID- 25115843
TI - Validation of an extended French version of ID MigraineTM as a migraine-screening
tool.
AB - INTRODUCTION: Migraine has a considerable social, economic, physical and
emotional burden but remains underdiagnosed and undertreated. A specific migraine
screening tool could help remove barriers to health care and be an attractive
instrument for epidemiological studies. The objective of this work was to assess
the validity of an extended French version of ID MigraineTM as a migraine
screening tool. METHODS: Sixty-seven subjects from the NESCaV study (2010-2012)
completed the migraine screen and were diagnosed by a neurologist specializing in
headache medicine using the International Classification of Headache Disorders,
2nd edition criteria (gold standard). Agreement between the two diagnoses was
evaluated by Cohen kappa coefficient (kappa). Sensitivity, specificity and
predictive values of the migraine screen were calculated. RESULTS: Migraine was
diagnosed in 21 (31.3%) of the 67 subjects according to the screening tool and in
24 (35.8%) by the neurologist (kappa = 0.90). The prevalence of migraine was
unrelated to age, gender, education and perception of financial resources.
Sensitivity and specificity of the screen were 87.5% and 100%, respectively. The
screen prevalence of migraine with aura was 10.4% (sensitivity and specificity:
83.3% and 96.7%, respectively). CONCLUSION: The extended French version of ID
MigraineTM (ef-ID Migraine) is a validated tool to screen migraine in French
speaking countries.
PMID- 25115844
TI - Antiepileptics in migraine prophylaxis: an updated Cochrane review.
AB - INTRODUCTION: The efficacy of several antiepileptics in the preventive treatment
of episodic migraine in adults has been systematically reviewed. Because many
trial reports have been published since then, an updated systematic review was
warranted. METHODS: We searched the Cochrane Central Register of Controlled
Trials, PubMed/MEDLINE (1966 to January 15, 2013), MEDLINE In-Process (current
week, January 15, 2013), and EMBASE (1974 to January 15, 2013) and hand-searched
Headache and Cephalalgia through January 2013. Prospective, controlled trials of
antiepileptics taken regularly to prevent the occurrence of migraine attacks, to
improve migraine-related quality of life, or both, were selected. RESULTS: Mean
headache frequency on topiramate and sodium valproate is significantly lower than
placebo. Likewise, topiramate and divalproex demonstrated favorable results for
the proportion of subjects with >= 50% reduction of migraine attacks. For
topiramate, 100 mg and 200 mg outperformed 50 mg, but this was paralleled by a
higher adverse event rate. For valproate/divalproex, a dose-effect correlation
could not be established. There was no unequivocal evidence of efficacy for any
of the other antiepileptics. CONCLUSION: Topiramate, sodium valproate and
divalproex are effective prophylactic treatments for episodic migraine in adults.
In contrast to previous reports, there is insufficient evidence to further
support the use of gabapentin.
PMID- 25115840
TI - Thromboembolic complications in inflammatory bowel disease.
AB - Patients with inflammatory bowel disease (IBD) have a 1.5-3.5-fold higher risk of
thromboembolism when compared to the non-IBD population and the risk is much more
prominent at the time of a flare. Arterial thromboembolism (ischemic stroke,
focal white matter ischemia, cardiac ischemia, peripheral vascular disease and
mesenteric ischemia) and venous thromboembolism (deep vein thrombosis and
pulmonary embolism, cerebral venous sinus thrombosis, retinal, hepatic, portal
and mesenteric vein thromboses) belong to the group of underestimated
extraintestinal complications in IBD patients, which are associated with a high
morbidity and mortality rate (the overall mortality is as high as 25 % per
episode). Thromboembolism occurs in younger patients compared to the non-IBD
population and has a high recurrence rate. Multiple risk factors are involved in
the etiopathogenesis, but the acquired ones play the key role. Congenital
alterations do not occur more frequently in IBD patients when compared to the non
IBD population. Standardized guidelines for the prophylaxis of thromboembolism in
IBD patients are urgently needed and these should be respected in clinical
practice to avoid preventable morbidity and mortality.
PMID- 25115846
TI - Prediction and validation of diffusion coefficients in a model drug delivery
system using microsecond atomistic molecular dynamics simulation and vapour
sorption analysis.
AB - Diffusion of small to medium sized molecules in polymeric medical device
materials underlies a broad range of public health concerns related to unintended
leaching from or uptake into implantable medical devices. However, obtaining
accurate diffusion coefficients for such systems at physiological temperature
represents a formidable challenge, both experimentally and computationally. While
molecular dynamics simulation has been used to accurately predict the diffusion
coefficients, D, of a handful of gases in various polymers, this success has not
been extended to molecules larger than gases, e.g., condensable vapours, liquids,
and drugs. We present atomistic molecular dynamics simulation predictions of
diffusion in a model drug eluting system that represent a dramatic improvement in
accuracy compared to previous simulation predictions for comparable systems. We
find that, for simulations of insufficient duration, sub-diffusive dynamics can
lead to dramatic over-prediction of D. We present useful metrics for monitoring
the extent of sub-diffusive dynamics and explore how these metrics correlate to
error in D. We also identify a relationship between diffusion and fast dynamics
in our system, which may serve as a means to more rapidly predict diffusion in
slowly diffusing systems. Our work provides important precedent and essential
insights for utilizing atomistic molecular dynamics simulations to predict
diffusion coefficients of small to medium sized molecules in condensed soft
matter systems.
PMID- 25115847
TI - Monolithic molecularly imprinted cryogel for lysozyme recognition.
AB - The application of molecularly imprinted polymers in the selective adsorption of
macromolecules such as proteins by monolithic protein-imprinted columns requires
a macroporous structure, which can be provided by cryogelation at low temperature
in which the formation of ice crystals gives a porous structure to the
molecularly imprinted polymer. In this study, we applied this technique to
synthesize lysozyme-imprinted polyacrylamide cryogels containing 8% w/v of total
monomers and 0.3% w/v of lysozyme. The synthesized cryogel was sponge-like and
elastic with very fast swelling and reshaping properties, showing a swelling
ratio of 24.5 +/- 3 and gel fraction yield of about 72%. It showed an imprinting
effect of 1.58 and a separation factor of 1.37 for cytochrome c as the competing
protein. Adsorption studies on the cryogel revealed that it follows the Langmuir
isotherm, with a maximum theoretical adsorption capacity of 36.3 mg lysozyme per
gram of cryogel. Additionally, it was shown that a salt-free rebinding solution
at low flow rate and pH = 7.0 is favorable for lysozyme rebinding. This kind of
monolithic column promises a wide range of application in separation of various
biomolecules due to its preparation simplicity, good rebinding characteristics,
and macroporosity.
PMID- 25115845
TI - Targeting catalase but not peroxiredoxins enhances arsenic trioxide-induced
apoptosis in K562 cells.
AB - Despite considerable efficacy of arsenic trioxide (As2O3) in acute promyelocytic
leukemia (APL) treatment, other non-APL leukemias, such as chronic myeloid
leukemia (CML), are less sensitive to As2O3 treatment. However, the underlying
mechanism is not well understood. Here we show that relative As2O3-resistant K562
cells have significantly lower ROS levels than As2O3-sensitive NB4 cells. We
compared the expression of several antioxidant enzymes in these two cell lines
and found that peroxiredoxin 1/2/6 and catalase are expressed at high levels in
K562 cells. We further investigated the possible role of peroxirdoxin 1/2/6 and
catalase in determining the cellular sensitivity to As2O3. Interestingly,
knockdown of peroxiredoxin 1/2/6 did not increase the susceptibility of K562
cells to As2O3. On the contrary, knockdown of catalase markedly enhanced As2O3
induced apoptosis. In addition, we provide evidence that overexpression of
BCR/ABL cannot increase the expression of PRDX 1/2/6 and catalase. The current
study reveals that the functional role of antioxidant enzymes is cellular context
and treatment agents dependent; targeting catalase may represent a novel strategy
to improve the efficacy of As2O3 in CML treatment.
PMID- 25115848
TI - Bright, highly water-soluble triazacyclononane europium complexes to detect
ligand binding with time-resolved FRET microscopy.
AB - Luminescent europium complexes are used in a broad range of applications as a
result of their particular emissive properties. The synthesis and application of
bright, highly water-soluble, and negatively charged sulfonic- or carboxylic acid
derivatives of para-substituted aryl-alkynyl triazacyclononane complexes are
described. Introduction of the charged solubilizing moieties suppresses cellular
uptake or adsorption to living cells making them applicable for labeling and
performing assays on membrane receptors. These europium complexes are applied to
monitor fluorescent ligand binding on cell-surface proteins with time-resolved
Forster resonance energy transfer (TR-FRET) assays in plate-based format and
using TR-FRET microscopy.
PMID- 25115850
TI - Biocatalytic potential of lipase from Staphylococcus sp. MS1 for
transesterification of jatropha oil into fatty acid methyl esters.
AB - An extracellular lipase producing isolate Staphylococcus sp. MS1 was optimized
for lipase production and its biocatalytic potential was assessed. Medium with
tributyrin (0.25 %) and without any exogenous inorganic nitrogen source was found
to be optimum for lipase production from Staphylococcus sp. MS1. The optimum pH
and temperature for lipase production were found to be pH 7 and 37 degrees C
respectively, showing lipase activity of 37.91 U. It showed good lipase
production at pH 6-8. The lipase was found to be stable in organic solvents like
hexane and petroleum ether, showing 98 and 88 % residual activity respectively.
The biotransformation using the concentrated enzyme in petroleum ether resulted
in the synthesis of fatty acid methyl esters like methyl oleate, methyl palmitate
and methyl stearate. Thus, the lipase under study has got the potential to bring
about transesterification of oils into methyl esters which can be exploited for
various biotechnological applications.
PMID- 25115852
TI - Assessment of atrial electromechanical delay and left atrial mechanical functions
in patients with psoriasis vulgaris.
AB - OBJECTIVES: Increased frequency of atrial fibrillation (AF) has been demonstrated
in psoriasis cases. Prolongation of the duration of atrial electromechanical
delay (AEMD) is a well-known characteristic of the atrium, which is vulnerable to
AF. In the current study, our aims are to investigate AEMD durations and
mechanical functions of the left atrium (LA) in patients with psoriasis. METHODS:
A total of 90 patients, 45 with psoriasis vulgaris and 45 as the control group,
were included in the study. Atrial electromechanical coupling (PA) and intra- and
inter-atrial electromechanical delay (IA-AEMD) were measured with tissue Doppler
echocardiography. P-wave dispersion (PWD) was calculated from the 12-lead
electrocardiogram. The severity of the disease was evaluated by the Psoriasis
Area and Severity Index. RESULTS: The durations of PA lateral and PA septal were
significantly high in the psoriasis group when compared with the control group
(47.7 +/- 9.8 vs. 57.1 +/- 8.4 msec, P < 0.001 and 38.6 +/- 9.9 vs. 43.6 +/- 8
msec, P = 0.016, respectively). The durations of IA-AEMD, intra-right
electromechanical delay, and intra-left electromechanical delay in the psoriasis
group were significantly prolonged compared with the control group (15.2 +/- 4.1
vs. 21.7 +/- 5.6 msec, P < 0.001; 6 +/- 2.5 vs. 8.7 +/- 2.7 msec, P < 0.001; and
9.1 +/- 3.9 vs. 13.5 +/- 5.2 msec, P < 0.001; respectively). PWD was
significantly higher in patients with psoriasis vulgaris compared with controls
(36.1 +/- 7.9 vs. 40.2 +/- 9.1 msec, P = 0.043). CONCLUSION: In the present
study, we found prolongation in the durations of AEMD and PWD in the psoriasis
group compared with the control group. These results might be an early predictor
of AF and other arrhythmias.
PMID- 25115853
TI - Analyte zone sharpening in pressurized capillary electrochromatography based on
electrophoretic migration under a heterogeneous field.
AB - Significant peak width reductions, or peak height enhancements, of angiotensins
were observed when a high voltage was applied to hydrophilic interaction
pressurized capillary electrochromatography using gradient elution with mobile
phases containing perchloric acid. The investigation using a contactless
conductivity detector revealed that perchloric acid was adsorbed on the surface
of the stationary phase, when the acetonitrile content in the mobile phase was
high, and released from the stationary phase by increasing the water content
during a gradient procedure. The released perchloric acid formed a highly
concentrated zone moving from the column inlet to the outlet. The
electrochromatographic behavior of the analytes, primarily electrophoretic
migration, was changed in this zone. As a consequence of the significant
variation in migration velocity of the analytes, the sample band width was
reduced similar fashion to on-capillary concentration in capillary
electrophoresis. Using this result, the reduction of band width and enhancement
in separation efficiency was demonstrated in reversed-phase pressurized
electrochromatography, in which the conductivity of the mobile phase was
significantly altered using a step gradient. The resolution between benzoic acid
and 1-naphthalene sulfonic acid was successfully improved from 2.7 to 4.3 by
using the band width reduction method based on field-amplified stacking.
PMID- 25115849
TI - The potential of transgenic green microalgae; a robust photobioreactor to produce
recombinant therapeutic proteins.
AB - Microalgae have been used in food, cosmetic, and biofuel industries as a natural
source of lipids, vitamins, pigments and antioxidants for a long time. Green
microalgae, as potent photobioreactors, can be considered as an economical
expression system to produce recombinant therapeutical proteins at large-scale
due to low cost of production and scaling-up capitalization owning to the
inexpensive medium requirement, fast growth rate, and the ease of manipulation.
These microalgae possess all benefit eukaryotic expression systems including the
ability of post-translational modifications required for proper folding and
stability of active proteins. Among the many items regarded as recombinant
protein production, this review compares the different expression systems with
green microalgae like Dunaliella by viewing the nuclear/chloroplast
transformation challenges/benefits, related selection markers/reporter genes, and
crucial factors/strategies affecting the increase of foreign protein expression
in microalgae transformants. Some important factors were discussed regarding the
increase of protein yielding in microalgae transformants including:
transformation-associated genotypic modifications, endogenous regulatory factors,
promoters, codon optimization, enhancer elements, and milking of recombinant
protein.
PMID- 25115854
TI - Carnosine inhibits the proliferation of human gastric cancer SGC-7901 cells
through both of the mitochondrial respiration and glycolysis pathways.
AB - Carnosine, a naturally occurring dipeptide, has been recently demonstrated to
possess anti-tumor activity. However, its underlying mechanism is unclear. In
this study, we investigated the effect and mechanism of carnosine on the cell
viability and proliferation of the cultured human gastric cancer SGC-7901 cells.
Carnosine treatment did not induce cell apoptosis or necrosis, but reduced the
proliferative capacity of SGC-7901 cells. Seahorse analysis showed SGC-7901 cells
cultured with pyruvate have active mitochondria, and depend on mitochondrial
oxidative phosphorylation more than glycolysis pathway for generation of ATP.
Carnosine markedly decreased the absolute value of mitochondrial ATP-linked
respiration, and reduced the maximal oxygen consumption and spare respiratory
capacity, which may reduce mitochondrial function correlated with proliferative
potential. Simultaneously, carnosine also reduced the extracellular acidification
rate and glycolysis of SGC-7901 cells. Our results suggested that carnosine is a
potential regulator of energy metabolism of SGC-7901 cells both in the anaerobic
and aerobic pathways, and provided a clue for preclinical and clinical evaluation
of carnosine for gastric cancer therapy.
PMID- 25115858
TI - Synthesis of alpha-aryl esters and nitriles: deaminative coupling of alpha
aminoesters and alpha-aminoacetonitriles with arylboronic acids.
AB - Transition-metal-free synthesis of alpha-aryl esters and nitriles using
arylboronic acids with alpha-aminoesters and alpha-aminoacetonitriles,
respectively, as the starting materials has been developed. The reaction
represents a rare case of converting C(sp(3))-N bonds into C(sp(3))-C(sp(2))
bonds. The reaction conditions are mild, demonstrate good functional-group
tolerance, and can be scaled up.
PMID- 25115857
TI - Improving post-stroke dysphagia outcomes through a standardized and
multidisciplinary protocol: an exploratory cohort study.
AB - Stroke is a major cause of dysphagia. Few studies to date have reported on
standardized multidisciplinary protocolized approaches to the management of post
stroke dysphagia. The aim of this retrospective cohort study was to evaluate the
impact of a standardized multidisciplinary protocol on clinical outcomes in
patients with post-stroke dysphagia. We performed retrospective chart reviews of
patients with post-stroke dysphagia admitted to the neurological ward of Verona
University Hospital from 2004 to 2008. Outcomes after usual treatment for
dysphagia (T- group) were compared versus outcomes after treatment under a
standardized diagnostic and rehabilitative multidisciplinary protocol (T+ group).
Outcome measures were death, pneumonia on X-ray, need for respiratory support,
and proportion of patients on tube feeding at discharge. Of the 378 patients
admitted with stroke, 84 had dysphagia and were enrolled in the study. A
significantly lower risk of in-hospital death (odds ratio [OR] 0.20 [0.53-0.78]),
pneumonia (OR 0.33 [0.10-1.03]), need for respiratory support (OR 0.48 [0.14
1.66]), and tube feeding at discharge (OR 0.30 [0.09-0.91]) was recorded for the
T+ group (N = 39) as compared to the T- group (N = 45). The adjusted OR showed no
difference between the two groups for in-hospital death and tube feeding at
discharge. Use of a standardized multidisciplinary protocolized approach to the
management of post-stroke dysphagia may significantly reduce rates of aspiration
pneumonia, in-hospital mortality, and tube feeding in dysphagic stroke survivors.
Consistent with the study's exploratory purposes, our findings suggest that the
multidisciplinary protocol applied in this study offers an effective model of
management of post-stroke dysphagia.
PMID- 25115856
TI - Functional swallowing outcomes in nasopharyngeal cancer treated with IMRT at 6 to
42 months post-radiotherapy.
AB - We sought to evaluate the swallowing function of 18 patients surviving
nasopharyngeal cancer, who had been treated using an intensity-modulated
radiotherapy (IMRT) protocol designed to minimise functional impairment. We
compared the outcomes of a patient-reported oral function score with fiberoptic
endoscopic examination of swallow (FEES), Australian Therapy Outcome Measures
(AusTOMs) and a measure of trismus. While all patients returned to a fully oral
diet, there was ongoing swallow dysfunction characterised by bolus residue and
delay, but no aspiration. Dysphagia was of mild or moderate severity on all
measures, generally because of the need for texture modification, impaired bolus
transit or dysgeusia. There was xerostomia on self-reported measurement combined
with reports of behaviours adaptive to xerostomia on AusTOMs; however, salivary
functioning was less impaired on FEES. There was no trismus in this cohort. Our
cohort lacked the morbidity experienced by cohorts reported in earlier studies,
potentially due to the use of IMRT.
PMID- 25115855
TI - Tetrandrine suppresses lipopolysaccharide-induced microglial activation by
inhibiting NF-kappaB and ERK signaling pathways in BV2 cells.
AB - BACKGROUND AND OBJECTIVE: Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid
extracted from Stephania tetrandra Moore. Recent studies have suggested that TET
can reduce the inflammatory response in microglia, but the mechanisms remain
unclear. The aim of this study is to investigate whether TET can inhibit
lipopolysaccharide (LPS)-induced microglial activation and clarify its possible
mechanisms. STUDY DESIGN/MATERIALS AND METHODS: Cell viability assays and cell
apoptosis assays were used to determine the working concentrations of TET. Then,
BV2 cells were seeded and pretreated with TET for 2 h. LPS was then added and
incubated for an additional 24 hours. qRT-PCR and ELISA were used to measure the
mRNA or protein levels of IL1beta and TNFalpha. Western blotting was utilized to
quantify the expression of CD11b and cell signaling proteins. RESULTS: TET at
optimal concentrations (0.1 uM, 0.5 uM or 1 uM) did not affect the cell
viability. After TET pretreatment, the levels of IL1beta and TNFalpha (both in
transcription and translation) were significantly inhibited in a dose-dependent
manner. Further studies indicated that phospho-p65, phospho-IKK, and phospho-ERK
1/2 expression were also suppressed by TET. CONCLUSIONS: Our results indicate
that TET can effectively suppress microglial activation and inhibit the
production of IL1beta and TNFalpha by regulating the NF-kB and ERK signaling
pathways. Together with our previous studies, we suggest that TET would be a
promising candidate to effectively suppress overactivated microglia and alleviate
neurodegeneration in glaucoma.
PMID- 25115860
TI - Different implication of elevated B-type natriuretic peptide level in patients
with heart failure with preserved ejection fraction and in those with reduced
ejection fraction.
AB - BACKGROUND: There have been no reports that show significant direct relationship
between echocardiographic parameters and B-type natriuretic peptide (BNP) level.
This could be due to the heterogeneous pathophysiology of heart failure and a
lack of appropriate echocardiographic parameters. We sought to determine the best
echocardiographic parameter that described elevated BNP level in patients with
heart failure with and without systolic dysfunction. METHODS AND RESULTS: We
studied 111 consecutive heart failure patients. They were divided into patients
with heart failure and preserved ejection fraction (HFPEF, n = 61) and that with
heart failure and reduced ejection fraction (HFREF, n = 50). Conventional and new
echocardiographic parameters including myocardial strains were measured. BNP did
not reflect any single echocardiographic parameter in patients with heart failure
in total. The ratio of early diastolic transmitral flow velocity and mitral
annular velocity had strong positive correlation with BNP level in the HFPEF
group but not in the HFREF group. In the group of HFREF, global longitudinal and
circumferential strains were positively correlated. Multivariate analysis
revealed that predicted factors for BNP value in HFPEF and in HFREF were
different. CONCLUSION: High BNP level may indicate high filling pressure when
ejection fraction is preserved and may indicate myocardial dysfunction when it is
reduced.
PMID- 25115862
TI - Interfacial dynamics in foams and emulsions.
PMID- 25115861
TI - Topoisomerase 2 is dispensable for the replication and segregation of small yeast
artificial chromosomes (YACs).
AB - DNA topoisomerases are thought to play a critical role in transcription,
replication and recombination as well as in the condensation and segregation of
sister duplexes during cell division. Here, we used high-resolution two
dimensional agarose gel electrophoresis to study the replication intermediates
and final products of small circular and linear minichromosomes of Saccharomyces
cerevisiae in the presence and absence of DNA topoisomerase 2. The results
obtained confirmed that whereas for circular minichromosomes, catenated sister
duplexes accumulated in the absence of topoisomerase 2, linear YACs were able to
replicate and segregate regardless of this topoisomerase. The patterns of
replication intermediates for circular and linear YACs displayed significant
differences suggesting that DNA supercoiling might play a key role in the
modulation of replication fork progression. Altogether, this data supports the
notion that for linear chromosomes the torsional tension generated by
transcription and replication dissipates freely throughout the telomeres.
PMID- 25115863
TI - Postoperative complications in bariatric surgery using age and BMI
stratification: a study using ACS-NSQIP data.
AB - BACKGROUND: Bariatric surgery results in long-term weight loss and significant
morbidity reduction. Morbidity and mortality following bariatric surgery remain
low and acceptable. This study looks to define the trend of morbidity and
mortality as it relates to increasing age and body mass index (BMI) in patients
undergoing bariatric surgery. METHODS: We queried the ACS/NSQIP 2010-2011 Public
Use File for patients who underwent elective laparoscopic adjustable banding
(LAGB), sleeve gastrectomy (LSG) and gastric bypass (LGBP). Total morbidity and
30-day mortality were evaluated. Logistic regression models were created to
estimate the effect of increasing age and BMI on morbidity for these bariatric
procedures. RESULTS: A total of 20,308 laparoscopic bariatric procedures were
reviewed (11617 LGBP, 3069 LSG and 5622 LAGB). Overall mortality and morbidity
rates were 0.11 and 3.84%, respectively. The odds of postoperative complications
increased by 2% with each additional year of age (OR 1.02, 95% CI 1.02-1.03) and
every point increase in BMI (OR 1.02, 95% CI 1.01-1.03). Multiple logistic
regression identified COPD, Diabetes, Hypertension, and Dyspnea as major risk
factors for postoperative morbidity. Postoperative complications were three times
more likely after LGBP (OR 2.87, 95% CI 2.31-3.57) and two times more likely
after LSG (OR 2.06, 95% CI 1.57-2.72) when compared to patients undergoing LAGB.
CONCLUSION: Morbidity and mortality increase on a predictable trend with
increasing age and BMI. There is increased risk of morbidity for stapling
procedures when compared to gastric banding, but this must be considered in
context of surgical efficacy when choosing a bariatric procedure. These data can
be used in preoperative counseling and evaluation of surgical candidacy of
bariatric surgical patients.
PMID- 25115864
TI - Superior mesenteric artery syndrome following sleeve gastrectomy: case report,
review of the literature, and video on technique for surgical correction.
AB - Superior mesenteric artery (SMA) syndrome is a rare condition in which the
duodenum is compressed between the SMA and aorta. This often occurs following
extreme weight loss and has been reported in the bariatric population. We present
the first reported case of SMA syndrome following sleeve gastrectomy. The patient
underwent laparoscopic duodenojejunostomy and recovered uneventfully. The
following is a review of the literature and detailed operative approach in the
attached video.
PMID- 25115865
TI - Pre-operative opioid analgesia reduces clinical success of laparoscopic gastric
electrical stimulation placement in patients with gastroparesis.
AB - INTRODUCTION: Gastroparesis is a common chronic and costly disorder for which
medical therapy is often unsuccessful. Gastric electrical stimulation (GES) has
been used to treat refractory cases, however, response is variable and difficult
to predict. This study aims to assess whether pre-operative opioid analgesics
(OA) use affects clinical success of GES. METHODS: Records of 128 patients who
underwent laparoscopic GES placement from March 2001 to September 2012 were
analyzed retrospectively. Data collected included demographics, surgical
outcomes, and clinical parameters. Pre- and post-operative opioid analgesic
dosing (No = 0 morphine equivalents (ME)/day, Low = 0-40 ME/day, Mid = 41-80
ME/day, High >80 ME/day), as well as clinical symptom assessment was collected
for up to 3 years post-operatively. Clinical success was defined as (1) OA
reduction of >50 %, (2) maintenance of weight, or (3) symptom improvement.
Descriptive statistics were computed for all factors. A p < 0.05 was considered
statistically significant. RESULTS: Fifty-three patients were on OA pre
operatively compared to 69 patients who were not. Patients not on OA pre
operatively were less likely than those on OA pre-op group to be on OA post
operatively (p = 0.005); however, there were no differences in weight or symptom
improvement. Sub-group analysis of the 53 patients on OA demonstrated significant
improvement in clinical symptoms in the low-morphine cohort compared to the mid
morphine cohort (p = 0.02), and OA dosing post-operatively in the low-morphine
cohort diminished significantly compared to mid- and high-morphine cohort (p =
0.032). There was no significant difference in weight. CONCLUSION: OA dosing pre
operatively significantly affects clinical success of GES placement. Criteria for
offering GES implantation may need to take OA dosing into consideration.
PMID- 25115866
TI - Bottom-up design of small molecules that stimulate exon 10 skipping in mutant
MAPT pre-mRNA.
AB - One challenge in chemical biology is to develop small molecules that control
cellular protein content. The amount and identity of proteins are influenced by
the RNAs that encode them; thus, protein content in a cell could be affected by
targeting mRNA. However, RNA has been traditionally difficult to target with
small molecules. In this report, we describe controlling the protein products of
the mutated microtubule-associated protein tau (MAPT) mature mRNA with a small
molecule. MAPT mutations in exon 10 are associated with inherited frontotemporal
dementia and Parkinsonism linked to chromosome 17 (FTDP-17), an incurable disease
that is directly caused by increased inclusion of exon 10 in MAPT mRNA. Recent
studies have shown that mutations within a hairpin at the MAPT exon 10-intron
junction decrease the thermodynamic stability of the RNA, increasing binding to
U1 snRNP and thus exon 10 inclusion. Therefore, we designed small molecules that
bind and stabilize a mutant MAPT by using Inforna, a computational approach based
on information about RNA-small-molecule interactions. The optimal compound
selectively bound the mutant MAPT hairpin and thermodynamically stabilized its
folding, facilitating exon 10 exclusion.
PMID- 25115867
TI - Cardiac strain during upright cycle ergometry in adolescent males.
AB - Little evidence exists with regard to changes in cardiac strain that occur during
submaximal exercise in young males. The aims of the study were to evaluate the
changes that occur in longitudinal (L), radial (R), and endocardial
circumferential (EC) strain during submaximal upright cycle ergometry and to
examine the test-retest reproducibility of these measurements. Fourteen
recreationally active, adolescent (age: 17.9 +/- 0.7 years) males volunteered for
the study. All subjects underwent an incremental (40 W) submaximal cycle
ergometer test. L, R, and EC strain values were obtained using speckle tracking,
from two-dimensional B-mode images of the left ventricle (LV) during rest and the
initial stages of submaximal exercise (40 and 80 W). The average of 6 LV segments
was used to determine both peak wall deformation (%) and the time to peak
deformation (ms). There was a statistically (P < 0.05) significant increase from
rest to submaximal exercise for peak deformation for L, R, and EC strain. There
was a statistically significant (P < 0.05) decrease from rest to submaximal
exercise for time to peak for L and R and EC strain and between submaximal
workloads for time to peak for L strain and EC strain. Coefficients of variation
demonstrated reproducibility for upright strain and strain rate measurements
similar to published supine measurements. This study has demonstrated that
changes in left ventricular wall deformation (L, R and EC strain) that occur
during the transition from rest to submaximal exercise can be reliably measured
and confirm that a healthy LV has a hyperdynamic response to exercise.
PMID- 25115868
TI - Cardiovascular disease-related parameters and oxidative stress in SHROB rats, a
model for metabolic syndrome.
AB - SHROB rats have been suggested as a model for metabolic syndrome (MetS) as a
situation prior to the onset of CVD or type-2 diabetes, but information on
descriptive biochemical parameters for this model is limited. Here, we
extensively evaluate parameters related to CVD and oxidative stress (OS) in SHROB
rats. SHROB rats were monitored for 15 weeks and compared to a control group of
Wistar rats. Body weight was recorded weekly. At the end of the study, parameters
related to CVD and OS were evaluated in plasma, urine and different organs. SHROB
rats presented statistically significant differences from Wistar rats in CVD risk
factors: total cholesterol, LDL-cholesterol, triglycerides, apoA1, apoB100,
abdominal fat, insulin, blood pressure, C-reactive protein, ICAM-1 and PAI-1. In
adipose tissue, liver and brain, the endogenous antioxidant systems were
activated, yet there was no significant oxidative damage to lipids (MDA) or
proteins (carbonylation). We conclude that SHROB rats present significant
alterations in parameters related to inflammation, endothelial dysfunction,
thrombotic activity, insulin resistance and OS measured in plasma as well as
enhanced redox defence systems in vital organs that will be useful as markers of
MetS and CVD for nutrition interventions.
PMID- 25115869
TI - Evaluation of [111In]-labeled zinc-dipicolylamine tracers for SPECT imaging of
bacterial infection.
AB - PURPOSE: This study prepared three structurally related zinc-dipicolylamine
(ZnDPA) tracers with [(111)In] labels and conducted biodistribution and single
photon emission computed tomography/computed tomography (SPECT/CT) imaging
studies of a mouse leg infection model. PROCEDURES: Two monovalent tracers, ZnDPA
[(111)In]DTPA and ZnDPA-[(111)In]DOTA, each with a single zinc-dipicolylamine
targeting unit, and a divalent tracer, Bis(ZnDPA)-[(111)In]DTPA, with two zinc
dipicolylamine units were prepared. Organ biodistribution and SPECT and CT
imaging studies were performed on living mice with a leg infection created by
injection of clinically relevant Gram positive Streptococcus pyogenes.
Fluorescent and luminescent Eu(3+)-labeled versions of these tracers were also
prepared and used to measure relative affinity for the exterior membrane surface
of bacterial cells and mimics of healthy mammalian cells. RESULTS: All three
(111)In-labeled radiotracers were prepared with a radiopurity of >90 %. The
biodistribution studies showed that the two monovalent tracers were cleared from
the body through the liver and kidney, with retained percentage injected dose for
all organs of <8 % at 20 h and infected leg target to non-target ratio (T/NT)
ratio of <=3.0. Clearance of the divalent tracer from the bloodstream was slower
and primarily through the liver, with a retained percentage injected dose for all
organs <37 % at 20 h and T/NT ratio rising to 6.2 after 20 h. The SPECT/CT
imaging indicated the same large difference in tracer pharmacokinetics and higher
accumulation of the divalent tracer at the site of infection. CONCLUSIONS: All
three [(111)In]-ZnDPA tracers selectively targeted the site of a clinically
relevant mouse infection model that could not be discerned by visual external
inspection of the living animal. The highest target selectivity, observed with a
divalent tracer equipped with two zinc-dipicolylamine targeting units, compares
quite favorably with the imaging selectivities previously reported for other
nuclear tracers that target bacterial cell surfaces. The tracer pharmacokinetics
depended heavily on tracer molecular structure suggesting that it may be possible
to rapidly fine tune the structural properties for optimized in vivo imaging
performance and clinical translation.
PMID- 25115871
TI - Evaluation of intravenous peramivir for treatment of influenza in hospitalized
patients.
AB - BACKGROUND: Seasonal influenza causes >200 000 annual hospitalizations in the
United States. Current antiviral treatment options are limited to oral or inhaled
agents. There is an urgent unmet need for intravenous antiviral treatments.
METHODS: Patients hospitalized with suspected influenza were randomized to 5-day
treatment with intravenous peramivir (600 mg once daily) or placebo; all received
the institution's standard of care (SOC) treatment. Time to clinical resolution
and change in viral shedding in nasopharyngeal specimens were the primary and key
secondary end points. RESULTS: Influenza infection was confirmed in 338 of 405
enrolled patients. At the time of a preplanned interim analysis, the primary
efficacy analysis population comprised 121 patients who did not receive a
concurrent neuraminidase inhibitor as part of the SOC. The median (95% confidence
interval) time to clinical resolution was 42.5 (34.0-57.9) hours for peramivir
versus 49.5 (40.0-61.9) hours for placebo (P = .97). A larger treatment effect
was observed in patients with history of symptoms <48 hours or admitted to an
intensive care unit. Greater reductions in viral shedding, based on median tissue
culture infective dose, were observed in patients who received peramivir than in
placebo recipients, although this difference was not statistically significant.
The incidence and severity of adverse events and laboratory abnormalities were
similar between the 2 treatment groups. The study was terminated for futility
after a preplanned interim analysis. CONCLUSIONS: A significant clinical benefit
was not demonstrated for peramivir plus SOC compared with placebo plus SOC.
Peramivir was generally safe and well tolerated. These findings highlight the
challenges in designing studies to evaluate influenza antiviral agents in a
hospitalized setting. Clinical Trials Registration. NCT00958776.
PMID- 25115872
TI - Added value of the emm-cluster typing system to analyze group A Streptococcus
epidemiology in high-income settings.
PMID- 25115870
TI - The South Asian genome.
AB - The genetic sequence variation of people from the Indian subcontinent who
comprise one-quarter of the world's population, is not well described. We carried
out whole genome sequencing of 168 South Asians, along with whole-exome
sequencing of 147 South Asians to provide deeper characterisation of coding
regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861
new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst
South Asians provides the first comprehensive map of genetic variation in this
major human population, and reveals evidence for selective pressures on genes
involved in skin biology, metabolism, infection and immunity. Our results will
accelerate the search for the genetic variants underlying susceptibility to
disorders such as type-2 diabetes and cardiovascular disease which are highly
prevalent amongst South Asians.
PMID- 25115873
TI - Using clinicians' search query data to monitor influenza epidemics.
AB - Search query information from a clinician's database, UpToDate, is shown to
predict influenza epidemics in the United States in a timely manner. Our results
show that digital disease surveillance tools based on experts' databases may be
able to provide an alternative, reliable, and stable signal for accurate
predictions of influenza outbreaks.
PMID- 25115874
TI - Irritable bowel syndrome and chronic fatigue 6 years after giardia infection: a
controlled prospective cohort study.
AB - BACKGROUND: Functional gastrointestinal disorders and fatigue may follow acute
infections. This study aimed to estimate the persistence, prevalence, and risk of
irritable bowel syndrome and chronic fatigue 6 years after Giardia infection.
METHODS: We performed a controlled prospective study of a cohort of 1252
individuals who had laboratory-confirmed Giardia infection during a waterborne
outbreak in 2004. In total, 748 cohort cases (exposed) and 878 matched controls
responded to a postal questionnaire 6 years later (in 2010). Responses were
compared to data from the same cohort 3 years before (in 2007). RESULTS: The
prevalences of irritable bowel syndrome (39.4%) by Rome III criteria and chronic
fatigue (30.8%) in the exposed group 6 years after giardiasis were significantly
elevated compared with controls, with adjusted relative risks (RRs) of 3.4 (95%
confidence interval [CI], 2.9-3.9) and 2.9 (95% CI, 2.3-3.4), respectively. In
the exposed group, the prevalence of irritable bowel syndrome decreased by 6.7%
(RR, 0.85 [95% CI, .77-.93]), whereas the prevalence of chronic fatigue decreased
by 15.3% from 3 to 6 years after Giardia infection (RR, 0.69 [95% CI, .62-.77]).
Giardia exposure was a significant risk factor for persistence of both
conditions, and increasing age was a risk factor for persisting chronic fatigue.
CONCLUSIONS: Giardia infection in a nonendemic setting is associated with an
increased risk for irritable bowel syndrome and chronic fatigue 6 years later.
The prevalences of both conditions decrease over time, indicating that this
intestinal protozoan parasite may elicit very long-term, but slowly self
limiting, complications.
PMID- 25115876
TI - Transplantation in autosomal recessive polycystic kidney disease: liver and/or
kidney?
AB - Autosomal recessive polycystic kidney disease (ARPKD) is characterized by
enlarged kidneys with dilated collecting ducts and congenital hepatic fibrosis.
There is a variable rate of progression of kidney and liver disease. Portal
hypertension and Caroli's disease occur from liver involvement that contributes
to morbidity and mortality. Approximately 40 % of patients have a severe disease
phenotype leading to rapid onset of end-stage kidney disease (ESKD) and signs of
portal hypertension and the rest may have predominant involvement of either the
kidney or liver. It is important for the physician to establish the extent of
organ involvement before deciding on the ultimate plan of management, especially
when transplantation is required. Isolated renal transplantation can be
considered when liver involvement is minimal. If hepatobiliary disease is
prominent, and kidney function is preserved, management options are based on
individual characteristics. In the presence of significant liver disease and
ESKD, consideration should be given to combined liver kidney transplantation,
which can be beneficial in eliminating the consequences of both kidney and liver
disease. However, this is a complex surgical procedure that needs to be performed
at experienced transplant centers. Improvement in surgical techniques has
considerably improved short-term graft survival with the added advantage of the
liver offering immunologic protection to the kidney allograft.
PMID- 25115875
TI - Peri-operative kidney injury and long-term chronic kidney disease following
orthotopic heart transplantation in children.
AB - Significant advances in cardiac intensive care including extracorporeal life
support have enabled children with complex congenital heart disease and end-stage
heart failure to be supported while awaiting transplantation. With an increasing
number of survivors after heart transplantation in children, the complications
from long-term immunosuppression, including renal insufficiency, are becoming
more apparent. Severe renal dysfunction after heart transplant is defined by a
serum creatinine level >2.5 mg/dL (221 MUmol/L), and/or need for dialysis or
renal transplant. The degree of renal dysfunction is variable and is progressive
over time. About 3-10 % of heart transplant recipients will go on to develop
severe renal dysfunction within the first 10 years post-transplantation. Multiple
risk factors for chronic kidney disease post-transplant have been identified,
which include pre-transplant worsening renal function, recipient demographics and
morbidity, peri-transplant haemodynamics and long-term exposure to calcineurin
inhibitors. Renal insufficiency increases the risk of post-transplant morbidity
and mortality. Hence, screening for renal dysfunction pre-, peri- and post
transplantation is important. Early and timely detection of renal insufficiency
may help minimize renal insults, and allow prompt implementation of
renoprotective strategies. Close monitoring and pre-emptive management of renal
dysfunction is an integral aspect of peri-transplant and subsequent post
transplant long-term care.
PMID- 25115883
TI - Tools in a clinical information system supporting clinical trials at a Swiss
University Hospital.
AB - BACKGROUND: Issues concerning inadequate source data of clinical trials rank
second in the most common findings by regulatory authorities. The increasing use
of electronic clinical information systems by healthcare providers offers an
opportunity to facilitate and improve the conduct of clinical trials and the
source documentation. We report on a number of tools implemented into the
clinical information system of a university hospital to support clinical
research. METHODS: In 2011/2012, a set of tools was developed in the clinical
information system of the University Hospital Zurich to support clinical
research, including (1) a trial registry for documenting metadata on the clinical
trials conducted at the hospital, (2) a patient-trial-assignment-tool to tag
patients in the electronic medical charts as participants of specific trials, (3)
medical record templates for the documentation of study visits and trial-related
procedures, (4) online queries on trials and trial participants, (5) access to
the electronic medical records for clinical monitors, (6) an alerting tool to
notify of hospital admissions of trial participants, (7) queries to identify
potentially eligible patients in the planning phase as trial feasibility checks
and during the trial as recruitment support, and (8) order sets to facilitate the
complete and accurate performance of study visit procedures. RESULTS: The number
of approximately 100 new registrations per year in the voluntary trial registry
in the clinical information system now matches the numbers of the existing
mandatory trial registry of the hospital. Likewise, the yearly numbers of
patients tagged as trial participants as well as the use of the standardized
trial record templates increased to 2408 documented trial enrolments and 190
reports generated/month in the year 2013. Accounts for 32 clinical monitors have
been established in the first 2 years monitoring a total of 49 trials in 16
clinical departments. A total of 15 months after adding the optional feature of
hospital admission alerts of trial participants, 107 running trials have
activated this option, including 48 out of 97 studies (49.5%) registered in the
year 2013, generating approximately 85 alerts per month. CONCLUSIONS: The
popularity of the presented tools in the clinical information system illustrates
their potential to facilitate the conduct of clinical trials. The tools also
allow for enhanced transparency on trials conducted at the hospital. Future
studies on monitoring and inspection findings will have to evaluate their impact
on quality and safety.
PMID- 25115881
TI - Postnatal hyperoxia exposure differentially affects hepatocytes and liver
haemopoietic cells in newborn rats.
AB - Premature newborns are frequently exposed to hyperoxic conditions and
experimental data indicate modulation of liver metabolism by hyperoxia in the
first postnatal period. Conversely, nothing is known about possible modulation of
growth factors and signaling molecules involved in other hyperoxic responses and
no data are available about the effects of hyperoxia in postnatal liver
haematopoiesis. The aim of the study was to analyse the effects of hyperoxia in
the liver tissue (hepatocytes and haemopoietic cells) and to investigate possible
changes in the expression of Vascular Endothelial Growth Factor (VEGF), Matrix
Metalloproteinase 9 (MMP-9), Hypoxia-Inducible Factor-1alpha (HIF-1alpha),
endothelial Nitric Oxide Synthase (eNOS), and Nuclear Factor-kB (NF-kB).
Experimental design of the study involved exposure of newborn rats to room air
(controls), 60% O2 (moderate hyperoxia), or 95% O2 (severe hyperoxia) for the
first two postnatal weeks. Immunohistochemical and Western blot analyses were
performed. Severe hyperoxia increased hepatocyte apoptosis and MMP-9 expression
and decreased VEGF expression. Reduced content in reticular fibers was found in
moderate and severe hyperoxia. Some other changes were specifically produced in
hepatocytes by moderate hyperoxia, i.e., upregulation of HIF-1alpha and
downregulation of eNOS and NF-kB. Postnatal severe hyperoxia exposure increased
liver haemopoiesis and upregulated the expression of VEGF (both moderate and
severe hyperoxia) and eNOS (severe hyperoxia) in haemopoietic cells. In
conclusion, our study showed different effects of hyperoxia on hepatocytes and
haemopoietic cells and differential involvement of the above factors. The
involvement of VEGF and eNOS in the liver haemopoietic response to hyperoxia may
be hypothesized.
PMID- 25115884
TI - Making data from clinical trials available.
PMID- 25115882
TI - The transitioning from trials to extended follow-up studies.
AB - BACKGROUND: Investigators may elect to extend follow-up of participants enrolled
in a randomized clinical trial after the trial comes to its planned end. The
additional follow-up may be initiated to learn about longer term effects of
treatments, including adverse events, costs related to treatment, or for reasons
unrelated to treatment such as to observe the natural course of the disease using
the established cohort from the trial. PURPOSE: We examine transitioning from
trials to extended follow-up studies when the goal of additional follow-up is to
observe longer term treatment effects. METHODS: We conducted a literature search
in selected journals from 2000 to 2012 to identify trials that extended follow-up
for the purpose of studying longer term treatment effects and extracted
information on the operational and logistical issues in the transition. We also
draw experience from three trials coordinated by the Johns Hopkins Coordinating
Centers that made transitions to extended follow-up: the Alzheimer's Disease Anti
inflammatory Prevention Trial, Multicenter Uveitis Steroid Treatment trial, and
Childhood Asthma Management Program. RESULTS: Transitions are not uncommon in
multicenter clinical trials, even in trials that continued to the planned end of
the trial. Transitioning usually necessitates new participant consents. If study
infrastructure is not maintained during the transition, participants will be lost
and re-establishing the staff and facilities will be costly. Merging data from
the trial and follow-up study can be complicated by changes in data collection
measures and schedules. LIMITATIONS: Our discussion and recommendations are
limited to issues that we have experienced in transitions from trials to follow
up studies. DISCUSSION: We discuss issues such as maintaining funding,
institutional review board and consent requirements, contacting participants, and
combining data from the trial and follow-up phases. We conclude with a list of
recommendations to facilitate transitions from a trial to an extended follow-up
study.
PMID- 25115885
TI - Trigeminal induced arousals during human sleep.
AB - BACKGROUND: Arousals caused by external stimuli during human sleep have been
studied for most of the sensorial systems. It could be shown that a pure nasal
trigeminal stimulus leads to arousals during sleep. The frequency of arousals
increases dependent on the stimulus concentration. The aim of the study was to
evaluate the influence of different stimulus durations on arousal frequency
during different sleep stages. METHODS: Ten young healthy volunteers with 20
nights of polysomnography were included in the study. Pure trigeminal stimulation
with both different concentrations of CO2 (0, 10, 20, 40% v/v) and different
stimulus durations (1, 3, 5, and 10 s) were applied during different sleep stages
to the volunteers using an olfactometer. The application was performed during
different sleep stages (light sleep, deep sleep, REM sleep). RESULTS: The number
of arousals increased with rising stimulus duration and stimulus concentration
during each sleep stage. CONCLUSION: Trigeminal stimuli during sleep led to
arousals in dose- and time-dependent manner.
PMID- 25115886
TI - Accuracy of a novel auto-CPAP device to evaluate the residual apnea-hypopnea
index in patients with obstructive sleep apnea.
AB - BACKGROUND: Patients under treatment with continuous positive airway pressure
(CPAP) may have residual sleep apnea (RSA). OBJECTIVE: The main objective of our
study was to evaluate a novel auto-CPAP for the diagnosis of RSA. METHODS: All
patients referred to the sleep laboratory to undergo CPAP polysomnography were
evaluated. Patients treated with oxygen or noninvasive ventilation and split
night polysomnography (PSG), PSG with artifacts, or total sleep time less than
180 min were excluded. The PSG was manually analyzed before generating the
automatic report from auto-CPAP. PSG variables (respiratory disturbance index
(RDI), obstructive apnea index, hypopnea index, and central apnea index) were
compared with their counterparts from auto-CPAP through Bland-Altman plots and
intraclass correlation coefficient. The diagnostic accuracy of autoscoring from
auto-CPAP using different cutoff points of RDI (>=5 and 10) was evaluated by the
receiver operating characteristics (ROCs) curve. RESULTS: The study included 114
patients (24 women; mean age and BMI, 59 years old and 33 kg/m(2); RDI and
apnea/hypopnea index (AHI)-auto median, 5 and 2, respectively). The average
difference between the AHI-auto and the RDI was -3.5 +/- 3.9. The intraclass
correlation coefficient (ICC) between the total number of central apneas,
obstructive, and hypopneas between the PSG and the auto-CPAP were 0.69, 0.16, and
0.15, respectively. An AHI-auto >2 (RDI >= 5) or >4 (RDI >= 10) had an area under
the ROC curve, sensitivity, specificity, positive likelihood ratio, and negative
for diagnosis of residual sleep apnea of 0.84/0.89, 84/81%, 82/91%, 4.5/9.5, and
0.22/0.2, respectively. CONCLUSIONS: The automatic analysis from auto-CPAP (S9
Autoset) showed a good diagnostic accuracy to identify residual sleep apnea. The
absolute agreement between PSG and auto-CPAP to classify the respiratory events
correctly varied from very low (obstructive apneas, hypopneas) to moderate
(central apneas).
PMID- 25115888
TI - Genetic studies reveal an unexpected negative regulatory role for Jak2 in
thrombopoiesis.
AB - JAK inhibitor treatment is limited by the variable development of anemia and
thrombocytopenia thought to be due to on-target JAK2 inhibition. We evaluated the
impact of Jak2 deletion in platelets (PLTs) and megakaryocytes (MKs) on blood
counts, stem/progenitor cells, and Jak-Stat signaling. Pf4-Cre-mediated Jak2
deletion in PLTs and MKs did not compromise PLT formation but caused
thrombocytosis, and resulted in expansion of MK progenitors and Lin(-)Sca1(+)Kit+
cells. Serum thrombopoietin (TPO) was maintained at normal levels in Pf4-Cre
positive Jak2(f/f) mice, consistent with reduced internalization/turnover by Jak2
deficient PLTs. These data demonstrate that Jak2 in terminal megakaryopoiesis is
not required for PLT production, and that Jak2 loss in PLTs and MKs results in
non-autonomous expansion of stem/progenitors and of MKs and PLTs via dysregulated
TPO turnover. This suggests that the thrombocytopenia frequently seen with JAK
inhibitor treatment is not due to JAK2 inhibition in PLTs and MKs, but rather due
to JAK2 inhibition in stem/progenitor cells.
PMID- 25115887
TI - Src family kinases: at the forefront of platelet activation.
AB - Src family kinases (SFKs) play a central role in mediating the rapid response of
platelets to vascular injury. They transmit activation signals from a diverse
repertoire of platelet surface receptors, including the integrin alphaIIbbeta3,
the immunoreceptor tyrosine-based activation motif-containing collagen receptor
complex GPVI-FcR gamma-chain, and the von Willebrand factor receptor complex GPIb
IX-V, which are essential for thrombus growth and stability. Ligand-mediated
clustering of these receptors triggers an increase in SFK activity and downstream
tyrosine phosphorylation of enzymes, adaptors, and cytoskeletal proteins that
collectively propagate the signal and coordinate platelet activation. A growing
body of evidence has established that SFKs also contribute to Gq- and Gi-coupled
receptor signaling that synergizes with primary activation signals to maximally
activate platelets and render them prothrombotic. Interestingly, SFKs
concomitantly activate inhibitory pathways that limit platelet activation and
thrombus size. In this review, we discuss past discoveries that laid the
foundation for this fundamental area of platelet signal transduction, recent
progress in our understanding of the distinct and overlapping functions of SFKs
in platelets, and new avenues of research into mechanisms of SFK regulation. We
also highlight the thrombotic and hemostatic consequences of targeting platelet
SFKs.
PMID- 25115890
TI - A staging system for renal outcome and early markers of renal response to
chemotherapy in AL amyloidosis.
AB - The kidney is involved in 70% of patients with immunoglobulin light-chain (AL)
amyloidosis, but little is known on progression or reversibility of renal
involvement, and criteria for renal response have never been validated. Newly
diagnosed patients from the Pavia (n = 461, testing cohort) and Heidelberg (n =
271, validation cohort) centers were included. Proteinuria >5 g/24 h and
estimated glomerular filtration rate (eGFR) <50 mL/min predicted progression to
dialysis best. Proteinuria below and eGFR above the thresholds indicated low risk
(0 and 4% at 3 years in the testing and validation cohorts, respectively). High
proteinuria and low eGFR indicated high risk (60% and 85% at 3 years). At 6
months, a >=25% eGFR decrease predicted poor renal survival in both cohorts and
was adopted as criterion for renal progression. A decrease in proteinuria by
>=30% or below 0.5 g/24 h without renal progression was the criterion for renal
response, being associated with longer renal survival in the testing and
validation populations. Hematologic very good partial or complete remission at 6
months improved renal outcome in both populations. We identified and validated a
staging system for renal involvement and criteria for early assessment of renal
response and progression in AL amyloidosis that should be used in clinical
practice and trial design.
PMID- 25115891
TI - KIR B haplotype donors confer a reduced risk for relapse after haploidentical
transplantation in children with ALL.
AB - We analyzed the influence of donor killer-cell immunoglobulin-like receptor (KIR)
gene haplotypes on the risk for relapse and the probability of event-free
survival (EFS) in children with acute lymphoblastic leukemia who received human
leukocyte antigen-haploidentical transplantation of ex vivo T-cell-depleted
peripheral blood stem cells. The KIR gene haplotype was evaluated in 85 donors,
and the KIR B content score was determined in the 63 KIR haplotype B donors.
Patients transplanted from a KIR haplotype B donor had a significantly better EFS
than those transplanted from a KIR haplotype A donor (50.6% vs 29.5%,
respectively; P = .033). Moreover, a high donor KIR B-content score was
associated with a significantly reduced risk for relapse (Log-rank test for
trend, P = .026). These data indicate that KIR genotyping should be included in
the donor selection algorithm for haploidentical transplantation in children with
acute lymphoblastic leukemia with the aim of choosing, whenever possible, a KIR
haplotype B donor with a high KIR B-content score.
PMID- 25115892
TI - Antiemetic therapy in Asia Pacific countries for patients receiving moderately
and highly emetogenic chemotherapy--a descriptive analysis of practice patterns,
antiemetic quality of care, and use of antiemetic guidelines.
AB - PURPOSE: This paper reports prescribing patterns for prophylaxis of chemotherapy
induced nausea and vomiting (CINV) after highly or moderately emetogenic
chemotherapy (HEC or MEC) for cancer in six Asia Pacific countries. METHODS: In a
prospective noninterventional study, 31 sites in Australia, China, India,
Singapore, South Korea, and Taiwan recorded details of CINV prophylaxis for the
acute phase (first 24 h) and delayed phase (days 2-5) after single-day HEC or MEC
for adult patients. Additional information on CINV prophylactic medications was
collected from 6-day patient diaries. Primary antiemetic therapies were defined
as corticosteroids, the 5-hydroxytryptamine-3 receptor antagonists (5HT3-RAs),
and neurokinin-1 receptor antagonists (NK1-RAs). RESULTS: Evaluable patients in
cycle 1 numbered 648 (318 [49%] HEC and 330 [51%] MEC) of mean (SD) age of 56
(12) years, including 58% women. For the acute phase after HEC, overall (and
country range), 96% (91-100%) of patients received a 5HT3-RA, 87% (70-100%) a
corticosteroid, and 43% (0-91%) an NK1-RA. CINV prophylaxis for the HEC delayed
phase was more variable: including 22% (7-65%) 5HT3-RA, 52% (12-93%)
corticosteroid, and 46% (0-88%) NK1-RA. For the MEC acute phase, 97% (87-100%) of
patients received 5HT3-RA and 86% (73-97%) a corticosteroid. For the MEC delayed
phase, 201 patients (61%) received a primary antiemetic, including 5HT3-RA (41%),
corticosteroid (37%), and/or NK1-RA (4%). CONCLUSIONS: The 5HT3-RAs were
prescribed consistently in all countries, while prescribing of other antiemetic
therapies was variable, and corticosteroids were under-prescribed for CINV
prophylaxis, particularly in the delayed phase.
PMID- 25115889
TI - The exosome complex establishes a barricade to erythroid maturation.
AB - Complex genetic networks control hematopoietic stem cell differentiation into
progenitors that give rise to billions of erythrocytes daily. Previously, we
described a role for the master regulator of erythropoiesis, GATA-1, in inducing
genes encoding components of the autophagy machinery. In this context, the
Forkhead transcription factor, Foxo3, amplified GATA-1-mediated transcriptional
activation. To determine the scope of the GATA-1/Foxo3 cooperativity, and to
develop functional insights, we analyzed the GATA-1/Foxo3-dependent transcriptome
in erythroid cells. GATA-1/Foxo3 repressed expression of Exosc8, a pivotal
component of the exosome complex, which mediates RNA surveillance and epigenetic
regulation. Strikingly, downregulating Exosc8, or additional exosome complex
components, in primary erythroid precursor cells induced erythroid cell
maturation. Our results demonstrate a new mode of controlling erythropoiesis in
which multiple components of the exosome complex are endogenous suppressors of
the erythroid developmental program.
PMID- 25115893
TI - Rationale and design of the Pan Australasian chemotherapy-induced emesis burden
of illness study.
AB - BACKGROUND: Preventing and managing chemotherapy-induced nausea and vomiting
(CINV) remain important goals. The objective of the Pan Australasian chemotherapy
induced emesis burden of illness (PrACTICE) study was to describe the incidence
of CINV after highly or moderately emetogenic chemotherapy (HEC or MEC) for
cancer in current clinical practice in Australia and five Asian countries (China,
India, Singapore, South Korea, and Taiwan). STUDY DESIGN: This prospective,
observational study of CINV was conducted at 31 sites in these six countries from
August 2011 through September 2012 and enrolled male and female adult patients
(>=18 years of age) naive to HEC and MEC who were scheduled to receive at least
two cycles of single-day chemotherapy. The primary effectiveness endpoint was
complete response, defined as no vomiting or use of rescue therapy, during
chemotherapy cycle 1 in the overall phase (0-120 h), acute phase (0-24 h), and
delayed phase (>24-120 h). Study outcomes were analyzed descriptively. Primary
outcomes, CINV incidence, and treatment patterns (chemotherapy, CINV prophylaxis,
rescue medication prescription, and rescue medication use) were assessed by phase
(overall, acute, delayed), by cycle (as appropriate), within and across
countries, and by level of chemotherapy emetogenicity (HEC vs. MEC). The impact
of CINV in cycle 1 on CINV in cycle 2 was analyzed for all patients with
evaluable data for cycle 2. No site-specific analyses were performed. The
remainder of this special series of papers reports on the results of this study.
PMID- 25115894
TI - The importance of biologically relevant microclimates in habitat suitability
assessments.
AB - Predicting habitat suitability under climate change is vital to conserving
biodiversity. However, current species distribution models rely on coarse scale
climate data, whereas fine scale microclimate data may be necessary to assess
habitat suitability and generate predictive models. Here, we evaluate disparities
between temperature data at the coarse scale from weather stations versus fine
scale data measured in microhabitats required for a climate-sensitive mammal, the
American pika (Ochotona princeps). We collected two years of temperature data in
occupied talus habitats predicted to be suitable (high elevation) and unsuitable
(low elevation) by the bioclimatic envelope approach. At low elevations, talus
surface and interstitial microclimates drastically differed from ambient
temperatures measured on-site and at a nearby weather station. Interstitial talus
temperatures were frequently decoupled from high ambient temperatures, resulting
in instantaneous disparities of over 30 degrees C between these two
measurements. Microhabitat temperatures were also highly heterogeneous, such that
temperature measurements within the same patch of talus were not more correlated
than measurements at distant patches. An experimental manipulation revealed that
vegetation cover may cool the talus surface by up to 10 degrees C during the
summer, which may contribute to this spatial heterogeneity. Finally, low
elevation microclimates were milder and less variable than typical alpine
habitat, suggesting that, counter to species distribution model predictions,
these seemingly unsuitable habitats may actually be better refugia for this
species under climate change. These results highlight the importance of fine
scale microhabitat data in habitat assessments and underscore the notion that
some critical refugia may be counterintuitive.
PMID- 25115895
TI - Nuclear magnetic resonance relaxivities: investigations of ultrahigh-spin
lanthanide clusters from 10 MHz to 1.4 GHz.
AB - Paramagnetic relaxation enhancement is often explored in magnetic resonance
imaging in terms of contrast agents and in biomolecular nuclear magnetic
resonance (NMR) spectroscopy for structure determination. New ultrahigh-spin
clusters are investigated with respect to their NMR relaxation properties. As
their molecular size and therefore motional correlation times as well as their
electronic properties differ significantly from those of conventional contrast
agents, questions about a comprehensive characterization arise. The relaxivity
was studied by field-dependent longitudinal and transverse NMR relaxometry of
aqueous solutions containing Fe(III)(10)Dy(III)(10) ultrahigh-spin clusters (spin
ground state 100/2). The high-field limit was extended to 32.9 T by using a 24 MW
resistive magnet and an ultrahigh-frequency NMR setup. Interesting relaxation
dispersions were observed; the relaxivities increase up to the highest available
fields, which indicates a complex interplay of electronic and molecular
correlation times.
PMID- 25115896
TI - Potential negative ecological effects of corridors.
AB - Despite many studies showing that landscape corridors increase dispersal and
species richness for disparate taxa, concerns persist that corridors can have
unintended negative effects. In particular, some of the same mechanisms that
underlie positive effects of corridors on species of conservation interest may
also increase the spread and impact of antagonistic species (e.g., predators and
pathogens), foster negative effects of edges, increase invasion by exotic
species, increase the spread of unwanted disturbances such as fire, or increase
population synchrony and thus reduce persistence. We conducted a literature
review and meta-analysis to evaluate the prevalence of each of these negative
effects. We found no evidence that corridors increase unwanted disturbance or non
native species invasion; however, these have not been well-studied concerns (1
and 6 studies, respectively). Other effects of corridors were more often studied
and yielded inconsistent results; mean effect sizes were indistinguishable from
zero. The effect of edges on abundances of target species was as likely to be
positive as negative. Corridors were as likely to have no effect on antagonists
or population synchrony as they were to increase those negative effects. We found
3 deficiencies in the literature. First, despite studies on how corridors affect
predators, there are few studies of related consequences for prey population size
and persistence. Second, properly designed studies of negative corridor effects
are needed in natural corridors at scales larger than those achievable in
experimental systems. Third, studies are needed to test more targeted hypotheses
about when corridor-mediated effects on invasive species or disturbance may be
negative for species of management concern. Overall, we found no overarching
support for concerns that construction and maintenance of habitat corridors may
result in unintended negative consequences. Negative edge effects may be
mitigated by widening corridors or softening edges between corridors and the
matrix. Other negative effects are relatively small and manageable compared with
the large positive effects of facilitating dispersal and increasing diversity of
native species.
PMID- 25115897
TI - The metabolism and growth of web forums.
AB - We view web forums as virtual living organisms feeding on user's clicks and
investigate how they grow at the expense of clickstreams. We find that PV(t) (the
number of page views in a given time period) and UV(t) (the number of unique
visitors in the time period) of the studied forums satisfy the law of the
allometric growth, i.e., PV(t) ~ UV(t)((theta). We construct clickstream networks
and explain the observed temporal dynamics of networks by the interactions
between nodes. We describe the transportation of clickstreams using the function
D(i) ~ T(i)(gamma), in which T(i) is the total amount of clickstreams passing
through node i and D(i) is the amount of the clickstreams dissipated from i to
the environment. It turns out that gamma, an indicator for the efficiency of
network dissipation, not only negatively correlates with theta, but also sets the
bounds for theta. In particular, 1/gamma > theta when 0 < gamma < 1 and 1/gamma <
theta when gamma > 1. Our findings have practical consequences. For example,
theta can be used as a measure of the "stickiness" of forums, which quantifies
the stable ability of forums to remain users "lock-in" on the forum. Meanwhile,
the correlation between gamma and theta provides a method to predict the long
term "stickiness" of forums from the clickstream data in a short time period.
Finally, we discuss a random walk model that replicates both of the allometric
growth PV(t) ~ UV(t)(theta) and the dissipation function D(i) ~ T(gamma)(i).
PMID- 25115898
TI - Concentrations and distribution of polybrominated diphenyl ethers (PBDEs) in
soils and plants from a deca-BDE manufacturing factory in China.
AB - Residues of polybrominated diphenyl ethers (PBDEs), including eight PBDE
congeners, were investigated in soils and plants from a deca-BDE manufacturing
factory located in the Shandong province of China to evaluate and discuss their
pollution level and distribution. Total concentrations in topsoil ranged from
17.0 to 146 MUg g(-1) dry weight (dw) with a mean value of 58.7 MUg g(-1) dw. BDE
209 was the dominant congener in soils, accounting for 55.63-99.27 % of the total
PBDEs. Concentrations and congener patterns in soils varied among different soil
depths. Concentration levels in topsoil are high and the heavy accumulation in
deep soil also can be observed, even for some sites, the concentrations in 50-100
cm depth are higher than in topsoil. In plant samples, total PBDE concentrations
and the proportion of BDE-209 were high (69.92-99.10 %). The extent of pollution
by PBDEs in the deca-BDE production factory was higher than in other regions, and
the environmental risk caused by the production of deca-BDE is of concern. This
is the first study to report pollution of PBDEs in soils and plants from the
vicinity of a deca-BDE manufacturing factory.
PMID- 25115899
TI - Removal of heavy metal species from industrial sludge with the aid of
biodegradable iminodisuccinic acid as the chelating ligand.
AB - High level of heavy metals in industrial sludge was the obstacle of sludge
disposal and resource recycling. In this study, iminodisuccinic acid (IDS), a
biodegradable chelating ligand, was used to remove heavy metals from industrial
sludge generated from battery industry. The extraction of cadmium, copper,
nickel, and zinc from battery sludge with aqueous solution of IDS was studied
under various conditions. It was found that removal efficiency greatly depends on
pH, chelating agent's concentration, as well as species distribution of metals.
The results showed that mildly acidic and neutral systems were not beneficial to
remove cadmium. About 68 % of cadmium in the sample was extracted at the molar
ratio of IDS to heavy metals 7:1 without pH adjustment (pH 11.5). Copper of 91.3
% and nickel of 90.7 % could be removed by IDS (molar ratio, IDS: metals = 1:1)
with 1.2 % phosphoric acid effectively. Removal efficiency of zinc was very low
throughout the experiment. Based on the experimental results, IDS could be a
potentially useful chelant for heavy metal removal from battery industry sludge.
PMID- 25115902
TI - Pollination syndromes in a specialised plant-pollinator interaction: does floral
morphology predict pollinators in Calceolaria?
AB - Pollination syndromes are defined as suites of floral traits evolved in response
to selection imposed by a particular group of pollinators (e.g., butterflies,
hummingbirds, bats). Although numerous studies demonstrated their occurrence in
plants pollinated by radically different pollinators, it is less known whether it
is possible to identify them within species pollinated by one functional
pollinator group. In such a framework, we expect floral traits to evolve also in
response to pollinator subgroups (e.g., species, genera) within that unique
functional group. On this, specialised pollination systems represent appropriate
case studies to test such expectations. Calceolaria is a highly diversified plant
genus pollinated by oil-collecting bees in genera Centris and Chalepogenus.
Variation in floral traits in Calceolaria has recently been suggested to reflect
adaptations to pollinator types. However, to date no study has explicitly tested
that observation. In this paper, we quantitatively test that hypothesis by
evaluating the presence of pollination syndromes within the specialised
pollination system formed by several Calceolaria and their insect pollinators. To
do so, we use multivariate approaches and explore the structural matching between
the morphology of 10 Calceolaria taxa and that of their principal pollinators.
Our results identify morphological matching between floral traits related to
access to the reward and insect traits involved in oil collection, confirming the
presence of pollinator syndromes in Calceolaria. From a general perspective, our
findings indicate that the pollination syndrome concept can be also extended to
the intra-pollinator group level.
PMID- 25115901
TI - Vaniprevir plus peginterferon alfa-2a and ribavirin in treatment-experienced
Japanese patients with hepatitis C virus genotype 1 infection: a randomized phase
II study.
AB - BACKGROUND: Vaniprevir (MK-7009) is a hepatitis C virus (HCV) non-structural 3/4a
protease inhibitor which significantly increases virologic response rates in HCV
genotype (GT) 1-infected patients when added to peginterferon and ribavirin (PR).
METHODS: This was a phase II, multicenter, double-blind, randomized, dose-ranging
study in Japanese patients with HCV GT1 infection and previous relapse. Patients
received twice daily vaniprevir 100, 300, or 600 mg, or placebo plus PR for 4
weeks then PR alone for 2 weeks. Further treatment with PR was continued up to a
maximum of 72 weeks. The primary endpoint was rapid virologic response (RVR;
undetectable HCV RNA at treatment week 4). RESULTS: Ninety patients completed 4
weeks of vaniprevir/placebo plus PR. Rates of RVR were significantly higher with
vaniprevir compared with placebo (86, 95, and 76 % in the vaniprevir 100-, 300-,
and 600-mg arms versus 20 % with control; p<0.001 for all comparisons). Rates of
SVR, an exploratory analysis, in the vaniprevir 100-, 300-, 600-mg, and control
arms were 95, 100, 100, and 72 %, respectively. No patient had virologic
breakthrough or non-response while receiving vaniprevir. There were no serious
adverse events (AEs) or discontinuations due to an AE during vaniprevir
treatment. Diarrhea and nausea were more common with vaniprevir 600 mg than
control or lower vaniprevir doses. CONCLUSION: The addition of vaniprevir to PR
was associated with an increase in RVR and SVR. Combined with a generally safe
and well-tolerated profile, these data supported the further evaluation of
vaniprevir in Japanese patients with HCV GT1 infection (#NCT00880763).
PMID- 25115904
TI - Locked-in biomimetic surface gradients that are tunable in size, density and
functionalization.
AB - Tuneable and stable surface-chemical gradients in supported lipid bilayers (SLBs)
hold great promise for a range of applications in biological sensing and
screening. Yet, until now, no method has been reported that provides temporal
control of SLB gradients. Herein we report on the development of locked-in SLB
gradients that can be tuned in space, time and density by applying a process to
control lipid phase behaviour, electric field and temperature. Stable gradients
of charged Texas-Red-, serine- or biotin-terminated lipids have been prepared.
For example, the Texas-Red surface density was varied from 0 to 2 mol %, while
the length was varied between several tens to several hundreds of microns. At
room temperature the gradients are shown to be stable up to 24 h, while at 60
degrees C the gradients could be erased in 30 min. Covalent and non-covalent
chemical modification of the gradients is demonstrated, for example, by FITC,
hexahistidine-tagged proteins, and SAv/biotin. The amenability to various
(bio)chemistries paves the way for novel SLB-based gradients, useful in sensing,
high-throughput screening and for understanding dynamic biological processes.
PMID- 25115903
TI - Brain damage in commercial breath-hold divers.
AB - BACKGROUND: Acute decompression illness (DCI) involving the brain (Cerebral DCI)
is one of the most serious forms of diving-related injuries which may leave
residual brain damage. Cerebral DCI occurs in compressed air and in breath-hold
divers, likewise. We conducted this study to investigate whether long-term breath
hold divers who may be exposed to repeated symptomatic and asymptomatic brain
injuries, show brain damage on magnetic resonance imaging (MRI). SUBJECTS AND
METHODS: Our study subjects were 12 commercial breath-hold divers (Ama) with long
histories of diving work in a district of Japan. We obtained information on their
diving practices and the presence or absence of medical problems, especially DCI
events. All participants were examined with MRI to determine the prevalence of
brain lesions. RESULTS: Out of 12 Ama divers (mean age: 54.9+/-5.1 years), four
had histories of cerebral DCI events, and 11 divers demonstrated ischemic lesions
of the brain on MRI studies. The lesions were situated in the cortical and/or
subcortical area (9 cases), white matters (4 cases), the basal ganglia (4 cases),
and the thalamus (1 case). Subdural fluid collections were seen in 2 cases.
CONCLUSION: These results suggest that commercial breath-hold divers are at a
risk of clinical or subclinical brain injury which may affect the long-term
neuropsychological health of divers.
PMID- 25115905
TI - Incorporating social and cultural significance of large old trees in conservation
policy.
AB - In addition to providing key ecological functions, large old trees are a part of
a social realm and as such provide numerous social-cultural benefits to people.
However, their social and cultural values are often neglected when designing
conservation policies and management guidelines. We believe that awareness of
large old trees as a part of human identity and cultural heritage is essential
when addressing the issue of their decline worldwide. Large old trees provide
humans with aesthetic, symbolic, religious, and historic values, as well as
concrete tangible benefits, such as leaves, branches, or nuts. In many cultures
particularly large trees are treated with reverence. Also, contemporary popular
culture utilizes the image of trees as sentient beings and builds on the ancient
myths that attribute great powers to large trees. Although the social and
cultural role of large old trees is usually not taken into account in
conservation, accounting for human-related values of these trees is an important
part of conservation policy because it may strengthen conservation by
highlighting the potential synergies in protecting ecological and social values.
PMID- 25115907
TI - Editor's choice, volume 111.
PMID- 25115906
TI - Implantable collamer lens versus iris-fixed phakic intraocular lens implantation
to correct myopia: a meta-analysis.
AB - This study is a meta-analysis comparing the efficacy, predictability, and safety
of correcting myopia via implantation of two types of phakic intraocular lens
(PIOLs): the implantable collamer lens (ICL) and iris-fixed PIOL. The Cochrane
library, Pubmed, and EMBASE were searched. Study selection, data exclusion, and
quality assessment were performed by two independent observers. The pooled
relative risk (RR), pooled standardized mean difference (SMD), and their 95%
confidence intervals (CIs) were used to compare lenses. Seven studies, involving
511 eyes, were included. The pooled SMD in postoperative uncorrected distance
visual acuity (UDVA) comparing ICLs to iris-fixed PIOLs was -0.22 (95% CI, -0.58
to 0.13; P = .22). The pooled RR values of UDVA of 20/20 or better and of 20/40
or better comparing ICLs to iris-fixed PIOLs were 1.15 (95% CI, 0.89 to 1.47; P =
.29) and 1.01 (95% CI, 0.95 to 1.08; P = .75), respectively. The pooled RR of
loss of best spectacle-corrected visual acuity (BSCVA) and gain in BSCVA
comparing ICLs to iris-fixed PIOLs were 1.20 (95% CI, 0.24 to 6.00; P = .82) and
1.14 (95% CI, 0.89 to 1.48; P = .31), respectively. The pooled RR comparing ICLs
to iris-fixed PIOLs was 0.78 (95% CI, 0.29 to 2.12; P = .63) for all reported
complications and 2.80 (95% CI, 1.04 to 7.52; P = .04) for severe complications.
The pooled RR of achieving a result within +/- 0.5 D (diopter) of the intended
target comparing ICLs to iris-fixed PIOLs was 1.35 (95% CI, 1.04 to 1.77; P =
.03). Overall, there is no significant difference in efficacy between the two
types of PIOLs or in safety, except that the ICL is associated with a greater
incidence of severe complications, especially anterior subcapsular cataract,
primarily in the Version 2 and Version 3 groups. However, ICL has better
predictability.
PMID- 25115908
TI - Effects of the duration of cold stratification on early life stages of the
Mediterranean alpine plant Silene ciliata.
AB - Cold stratification provided by snow cover is essential to break seed dormancy in
many alpine plant species. The forecast reduction in snow precipitation and snow
cover duration in most temperate mountains as a result of global warming could
threaten alpine plant populations, especially those at the edge of their species
distribution, by altering the dynamics of early life stages. We simulated some
effects of a reduction in the snow cover period by manipulating the duration of
cold stratification in seeds of Silene ciliata, a Mediterranean alpine
specialist. Seeds from three populations distributed along an altitudinal
gradient were exposed to different periods of cold stratification (2, 4 and 6
months) in the laboratory and then moved to common garden conditions in a
greenhouse. The duration of the cold stratification treatment and population
origin significantly affected seed emergence percentage, emergence rate and
seedling size, but not the number of seedling leaves. The 6-month and 4-month
cold stratification treatments produced higher emergence percentages and faster
emergence rates than seeds without cold stratification treatment. No significant
cold stratification duration x seed population origin interactions were found,
thus differential sensitivity to cold stratification along elevation is not
supported.
PMID- 25115910
TI - Preventing aspiration during peroral endoscopic myotomy.
PMID- 25115909
TI - Invertebrate extracellular phagocyte traps show that chromatin is an ancient
defence weapon.
AB - Controlled release of chromatin from the nuclei of inflammatory cells is a
process that entraps and kills microorganisms in the extracellular environment.
Now termed ETosis, it is important for innate immunity in vertebrates.
Paradoxically, however, in mammals, it can also contribute to certain
pathologies. Here we show that ETosis occurs in several invertebrate species,
including, remarkably, an acoelomate. Our findings reveal that the phenomenon is
primordial and predates the evolution of the coelom. In invertebrates, the
released chromatin participates in defence not only by ensnaring microorganisms
and externalizing antibacterial histones together with other haemocyte-derived
defence factors, but crucially, also provides the scaffold on which intact
haemocytes assemble during encapsulation; a response that sequesters and kills
potential pathogens infecting the body cavity. This insight into the early origin
of ETosis identifies it as a very ancient process that helps explain some of its
detrimental effects in mammals.
PMID- 25115911
TI - Effectiveness of low emission zones: large scale analysis of changes in
environmental NO2, NO and NOx concentrations in 17 German cities.
AB - BACKGROUND: Low Emission Zones (LEZs) are areas where the most polluting vehicles
are restricted from entering. The effectiveness of LEZs to lower ambient
exposures is under debate. This study focused on LEZs that restricted cars of
Euro 1 standard without appropriate retrofitting systems from entering and
estimated LEZ effects on NO2, NO, and NOx ( = NO2+NO). METHODS: Continuous half
hour and diffuse sampler 4-week average NO2, NO, and NOx concentrations measured
inside and outside LEZs in 17 German cities of 6 federal states (2005-2009) were
analysed as matched quadruplets (two pairs of simultaneously measured index
values inside LEZ and reference values outside LEZ, one pair measured before and
one after introducing LEZs with time differences that equal multiples of 364
days) by multiple linear and log-linear fixed-effects regression modelling
(covariables: e.g., wind velocity, amount of precipitation, height of inversion
base, school holidays, truck-free periods). Additionally, the continuous half
hour data was collapsed into 4-week averages and pooled with the diffuse sampler
data to perform joint analysis. RESULTS: More than 3,000,000 quadruplets of
continuous measurements (half-hour averages) were identified at 38 index and 45
reference stations. Pooling with diffuse sampler data from 15 index and 10
reference stations lead to more than 4,000 quadruplets for joint analyses of 4
week averages. Mean LEZ effects on NO2, NO, and NOx concentrations (reductions)
were estimated to be at most -2 ug/m(3) (or -4%). The 4-week averages of NO2
concentrations at index stations after LEZ introduction were 55 ug/m(3) (median
and mean values) or 82 ug/m(3) (95th percentile). CONCLUSIONS: This is the first
study investigating comprehensively the effectiveness of LEZs to reduce NO2, NO,
and NOx concentrations controlling for most relevant potential confounders. Our
analyses indicate that there is a statistically significant, but rather small
reduction of NO2, NO, and NOx concentrations associated with LEZs.
PMID- 25115913
TI - Overlapped sequence types (STs) and serogroups of avian pathogenic (APEC) and
human extra-intestinal pathogenic (ExPEC) Escherichia coli isolated in Brazil.
AB - Avian pathogenic Escherichia coli (APEC) strains belong to a category that is
associated with colibacillosis, a serious illness in the poultry industry
worldwide. Additionally, some APEC groups have recently been described as
potential zoonotic agents. In this work, we compared APEC strains with
extraintestinal pathogenic E. coli (ExPEC) strains isolated from clinical cases
of humans with extra-intestinal diseases such as urinary tract infections (UTI)
and bacteremia. PCR results showed that genes usually found in the ColV plasmid
(tsh, iucA, iss, and hlyF) were associated with APEC strains while fyuA, irp-2,
fepC sitDchrom, fimH, crl, csgA, afa, iha, sat, hlyA, hra, cnf1, kpsMTII,
clpVSakai and malX were associated with human ExPEC. Both categories shared nine
serogroups (O2, O6, O7, O8, O11, O19, O25, O73 and O153) and seven sequence types
(ST10, ST88, ST93, ST117, ST131, ST155, ST359, ST648 and ST1011). Interestingly,
ST95, which is associated with the zoonotic potential of APEC and is spread in
avian E. coli of North America and Europe, was not detected among 76 APEC
strains. When the strains were clustered based on the presence of virulence
genes, most ExPEC strains (71.7%) were contained in one cluster while most APEC
strains (63.2%) segregated to another. In general, the strains showed distinct
genetic and fingerprint patterns, but avian and human strains of ST359, or ST23
clonal complex (CC), presented more than 70% of similarity by PFGE. The results
demonstrate that some "zoonotic-related" STs (ST117, ST131, ST10CC, ST23CC) are
present in Brazil. Also, the presence of moderate fingerprint similarities
between ST359 E. coli of avian and human origin indicates that strains of this ST
are candidates for having zoonotic potential.
PMID- 25115916
TI - Efficacy and safety of lixisenatide in elderly (>=65 years old) and very elderly
(>=75 years old) patients with type 2 diabetes: an analysis from the GetGoal
phase III programme.
AB - BACKGROUND: The objective of this article is to evaluate the pharmacokinetics,
efficacy and safety of lixisenatide (subcutaneous injection) in elderly (>=65
years old) and very elderly (>=75 years old) patients with type 2 diabetes
mellitus. METHODS: We conducted a phase I, single-centre, open-label study to
evaluate the safety and pharmacokinetics of a single lixisenatide 20 ug dose and
a pooled analysis of six randomized, placebo-controlled, phase III studies (12
month or 24-month duration) that evaluated glycaemic parameters and safety in
patients receiving lixisenatide 20 ug once daily or placebo. RESULTS: The
pharmacokinetics study included 36 healthy subjects, including 18 elderly healthy
subjects (>=65 years old) and 18 matched young healthy subjects (18-45 years
old). The pooled analysis included 3188 patients, including 2565 patients <65
years old and 623 patients >=65 years old (including 79 patients >=75 years old).
Mean exposure with lixisenatide 20 ug was ~30% higher in elderly than in young
subjects, and the terminal half-life was prolonged by ~1.6 times. Maximum
concentration (C(max)) and time to C(max) (t(max)) were comparable in both
groups. Equal numbers of elderly and young subjects reported treatment-emergent
adverse events, the majority of which were gastrointestinal disorders. In the
pooled analysis, lixisenatide 20 ug once daily provided significant reductions in
HbA1c versus placebo for all age groups. There was a similar incidence of
treatment-emergent adverse events across all age groups (range: 69-73%). The
incidence of symptomatic hypoglycaemia was generally comparable between
lixisenatide-treated and placebo-treated patients. CONCLUSION: These data suggest
that lixisenatide is effective and well tolerated in elderly and very elderly
patients with type 2 diabetes mellitus.
PMID- 25115915
TI - Assessment, validation and deployment strategy of a two-barcode protocol for
facile genotyping of duckweed species.
AB - Lemnaceae, commonly called duckweeds, comprise a diverse group of floating
aquatic plants that have previously been classified into 37 species based on
morphological and physiological criteria. In addition to their unique
evolutionary position among angiosperms and their applications in biomonitoring,
the potential of duckweeds as a novel sustainable crop for fuel and feed has
recently increased interest in the study of their biodiversity and systematics.
However, due to their small size and abbreviated structure, accurate typing of
duckweeds based on morphology can be challenging. In the past decade, attempts to
employ molecular barcoding techniques for species assignment have produced
promising results; however, they have yet to be codified into a simple and
quantitative protocol. A study that compiles and compares the barcode sequences
within all known species of this family would help to establish the fidelity and
limits of this DNA-based approach. In this work, we compared the level of
conservation between over 100 strains of duckweed for two intergenic barcode
sequences derived from the plastid genome. By using over 300 sequences publicly
available in the NCBI database, we determined the utility of each of these two
barcodes for duckweed species identification. Through sequencing of these
barcodes from additional accessions, 30 of the 37 known species of duckweed could
be identified with varying levels of confidence using this approach. From our
analyses using this reference dataset, we also confirmed two instances where mis
assignment of species has likely occurred. Potential strategies for further
improving the scope of this technology are discussed.
PMID- 25115917
TI - Osteoporotic L1 burst fracture treated by short-segment percutaneous
stabilization with cement-augmented screws and kyphoplasty (hybrid technique).
PMID- 25115914
TI - TRF1 and TRF2 differentially modulate Rad51-mediated telomeric and nontelomeric
displacement loop formation in vitro.
AB - A growing body of literature suggests that the homologous recombination/repair
(HR) pathway cooperates with components of the shelterin complex to promote both
telomere maintenance and nontelomeric HR. This may be due to the ability of both
HR and shelterin proteins to promote strand invasion, wherein a single-stranded
DNA (ssDNA) substrate base pairs with a homologous double-stranded DNA (dsDNA)
template displacing a loop of ssDNA (D-loop). Rad51 recombinase catalyzes D-loop
formation during HR, and telomere repeat binding factor 2 (TRF2) catalyzes the
formation of a telomeric D-loop that stabilizes a looped structure in telomeric
DNA (t-loop) that may facilitate telomere protection. We have characterized this
functional interaction in vitro using a fluorescent D-loop assay measuring the
incorporation of Cy3-labeled 90-nucleotide telomeric and nontelomeric substrates
into telomeric and nontelomeric plasmid templates. We report that preincubation
of a telomeric template with TRF2 inhibits the ability of Rad51 to promote
telomeric D-loop formation upon preincubation with a telomeric substrate. This
suggests Rad51 does not facilitate t-loop formation and suggests a mechanism
whereby TRF2 can inhibit HR at telomeres. We also report a TRF2 mutant lacking
the dsDNA binding domain promotes Rad51-mediated nontelomeric D-loop formation,
possibly explaining how TRF2 promotes nontelomeric HR. Finally, we report
telomere repeat binding factor 1 (TRF1) promotes Rad51-mediated telomeric D-loop
formation, which may facilitate HR-mediated replication fork restart and explain
why TRF1 is required for efficient telomere replication.
PMID- 25115918
TI - The NeckPix((c)): development of an evaluation tool for assessing kinesiophobia
in subjects with chronic neck pain.
AB - PURPOSE: To develop and validate NeckPix((c)), a multi-image instrument for
assessing daily activities in the context of pain-related fear, in order to allow
its use in patients with chronic neck pain (NP). METHODS: The measure was
developed by means of item generation followed by reduction/selection. The
psychometric testing included exploratory factor analysis; content validity by
investigating clarity, specificity, appropriateness for the target population,
relevance and completeness; reliability by internal consistency (Cronbach's
alpha) and test-retest stability (intra-class coefficient correlation, ICC); and
construct validity by comparing NeckPix with the Tampa Scale of Kinesiophobia
(TSK), the Pain Catastrophising Scale (PCS), the Neck Disability Index (NDI) and
a Numerical Rating Scale of pain intensity (NRS) (Pearson's correlation).
RESULTS: The measure, which includes ten images used to assess everyday
activities in the context of pain-related fear, was administered to 118 subjects
with chronic non-specific NP, and proved to be acceptable and feasible. Factor
analysis revealed a one-factor solution (which explained 71.12 % of variance).
The content of the images was considered adequate, appropriate for the target
population, comprehensive, and relevant for evaluating activity-related
kinesiophobia. The instrument's internal consistency was good (alpha = 0.954), as
was its test-retest stability (ICC 0.979). Construct validity demonstrated a
close correlation with the TSK (r = 0.759), and moderate correlations with the
PCS (r = 0.583), the NDI (r = 0.520), and a NRS (r = 0.455). CONCLUSION:
NeckPix((c)), which was successfully developed following international
recommendations, proved to have a good factorial structure and satisfactory
psychometric properties. Its use is recommended for research purposes.
PMID- 25115921
TI - Epidemiology of partial urorectal septum malformation sequence (or 'persistent
cloaca'): a population-based study in seven regions of England and Wales, 1985
2010.
AB - BACKGROUND: Partial urorectal septum malformation (pURSM) sequence (or
'persistent cloaca') is a rare congenital anomaly characterised by a joining of
the urethral, anal, and genital openings into a single common channel. This study
describes the epidemiology of pURSM sequence in England and Wales including
prevalence, additional anomalies, and pregnancy outcomes. METHODS: All cases of
pURSM sequence prospectively notified to seven congenital anomaly registers in
England and Wales during 1985-2010, whether delivered as live births, spontaneous
fetal deaths (>=20 weeks' gestation), or elective terminations of pregnancy for
fetal anomaly (TOPFA, any gestation), formed this population-based cohort. The
risks of spontaneous fetal and infant death were examined by Kaplan-Meier
analysis. Differences in prevalence over time, and between regions, were examined
by multilevel Poisson regression. RESULTS: 117 cases were recorded among
4,251,241 total births. Six (5%) pregnancies resulted in spontaneous fetal
deaths, 53 (45%) in TOPFA, and 58 (50%) in live births. The prevalence was 2.8
(95% CI 2.3 to 3.4) per 100,000 total births, increasing significantly over time
(p=0.002) and differing significantly between regions (p=0.005). 77 cases (66%)
had at least one additional major congenital anomaly outside the perineum,
including 67 (57%) renal, 29 (25%) musculoskeletal, 26 (23%) digestive system,
and 24 (21%) cardiovascular anomalies. The risks of spontaneous fetal and infant
death were estimated as 8.9% (95% CI 4.1 to 18.8) and 26.3% (95% CI 15.1 to 43.4)
respectively. CONCLUSIONS: This is the largest study of the epidemiology of pURSM
sequence. The information will be valuable for families and health professionals
whenever a case of pURSM sequence is diagnosed.
PMID- 25115920
TI - Mesenchymal stromal cell proliferation, gene expression and protein production in
human platelet-rich plasma-supplemented media.
AB - BACKGROUND: Platelet-rich plasma (PRP) is increasingly used as a cell culture
supplement, in order to reduce the contact of human cells with animal-derived
products during in vitro expansion. The effect of supplementation changes on cell
growth and protein production is not fully characterized. METHODS: Human
mesenchymal stromal cells from bone marrow, adipose tissue and Wharton's Jelly
were isolated and cultured in PRP-supplemented media. Proliferation, in vitro
differentiation, expression of cell surface markers, mRNA expression of key genes
and protein secretion were quantified. RESULTS: 10% PRP sustained five to tenfold
increased cell proliferation as compared to 10% fetal bovine serum. Regarding
cell differentiation, PRP reduced adipogenic differentiation and increased
calcium deposits in bone marrow and adipose tissue-mesenchymal stromal cells.
Wharton's Jelly derived mesenchymal stromal cells secreted higher concentrations
of chemokines and growth factors than other mesenchymal stromal cells when
cultured in PRP-supplemented media. Bone marrow derived mesenchymal stromal cells
secreted higher concentrations of pro-inflammatory and pro-angiogenic proteins.
Mesenchymal stromal cells isolated from adipose tissue secreted higher amounts of
extracellular matrix components. CONCLUSIONS: Mesenchymal stromal cells purified
from different tissues have distinct properties regarding differentiation,
angiogenic, inflammatory and matrix remodeling potential when cultured in PRP
supplemented media. These abilities should be further characterized in order to
choose the best protocols for their therapeutic use.
PMID- 25115924
TI - Senior doctor was present in 87% of anaesthesia cases in 2013.
PMID- 25115923
TI - YAP inhibits squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma
through ZEB2-dependent DNp63 repression.
AB - Whether the Hippo pathway contributes to cell lineage transition under
pathological conditions, especially tumorigenesis, remains largely unknown. Here
we show that YAP, the major effector of the Hippo pathway, displays a distinct
activation pattern in lung adenocarcinoma (ADC) and squamous cell carcinoma
(SCC); YAP is initially activated by LKB1 loss in lung ADC, which upregulates
ZEB2 expression and represses DNp63 transcription in a default manner. During
transdifferentiation, YAP is inactivated, which in turn relieves ZEB2-mediated
default repression of DNp63 and triggers squamous differentiation reprogramming.
Disruption of the YAP barrier for phenotypic transition significantly accelerates
squamous transdifferentiation, whereas constitutive YAP activation conversely
inhibits this transition. More importantly, ectopic DNp63 expression rescues the
inhibitory effect of YAP on squamous transdifferentiation. These findings have
established YAP as an essential barrier for lung cancer cell fate conversion and
provided a mechanism for regulating cancer plasticity, which might hold important
implication for YAP-targeted therapies.
PMID- 25115925
TI - Macrophage phenotype is associated with disease severity in preterm infants with
chronic lung disease.
AB - BACKGROUND: The etiology of persistent lung inflammation in preterm infants with
chronic lung disease of prematurity (CLD) is poorly characterized, hampering
efforts to stratify prognosis and treatment. Airway macrophages are important
innate immune cells with roles in both the induction and resolution of tissue
inflammation. OBJECTIVES: To investigate airway innate immune cellular phenotypes
in preterm infants with respiratory distress syndrome (RDS) or CLD. METHODS:
Bronchoalveolar lavage (BAL) fluid was obtained from term and preterm infants
requiring mechanical ventilation. BAL cells were phenotyped by flow cytometry.
RESULTS: Preterm birth was associated with an increase in the proportion of non
classical CD14(+)/CD16(+) monocytes on the day of delivery (58.9 +/- 5.8% of
total mononuclear cells in preterm vs 33.0 +/- 6.1% in term infants, p = 0.02).
Infants with RDS were born with significantly more CD36(+) macrophages compared
with the CLD group (70.3 +/- 5.3% in RDS vs 37.6 +/- 8.9% in control, p = 0.02).
At day 3, infants born at a low gestational age are more likely to have greater
numbers of CD14(+) mononuclear phagocytes in the airway (p = 0.03), but fewer of
these cells are functionally polarized as assessed by HLA-DR (p = 0.05) or CD36
(p = 0.05) positivity, suggesting increased recruitment of monocytes or a failure
to mature these cells in the lung. CONCLUSIONS: These findings suggest that
macrophage polarization may be affected by gestational maturity, that more
immature macrophage phenotypes may be associated with the progression of RDS to
CLD and that phenotyping mononuclear cells in BAL could predict disease outcome.
PMID- 25115927
TI - One-year outcome from an all-comers population of patients with ST-segment
elevation myocardial infarction treated with biolimus-eluting stent with
biodegradable polymer.
AB - OBJECTIVES: To evaluate the performance of biolimus-eluting stent (BES) in
patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous
coronary intervention (PCI) in a real world clinical scenario. BACKGROUND:
Randomized studies suggest that the BES with biodegradable polymer is more
effective and safe than early generation coronary stents in patients with STEMI.
METHODS: We included all consecutive STEMI patients undergoing PCI in this
prospective, multicenter registry. The primary endpoint of the study was the rate
of major adverse cardiac events (MACE), a composite of cardiac death, recurrent
myocardial infarction and ischemia-driven target vessel revascularization at 1
year follow-up. RESULTS: Between June and December 2012 we enrolled 311 STEMI
patients. The primary endpoint occurred in 3.2% (95% confidence interval: 1.6
5.8) of patients: cardiac death, re-infarction, and ischemia-driven TVR occurred
in 2.3%, 1.3%, and 0.6% of patients, respectively. One-year MACE-free survival
was 96.8% +/- 1.0%. CONCLUSIONS: In a real-world cohort of STEMI patients
undergoing PCI, the use of BES is associated with good 1-year clinical outcome.
These results confirm and expand previous findings showing the efficacy and
safety of BES in the setting of randomized trials.
PMID- 25115928
TI - Diaphragmatic hernia caused by heterotopic endometriosis in Chilaiditi syndrome:
report of a case.
AB - A 50-year-old Japanese female was admitted to our hospital because of ileus due
to Chilaiditi syndrome. Her symptoms did not improve with conservative therapy,
so chest and abdominal computed tomography (CT) was performed on the fifth day
after hospital admission. A diagnosis of incarceration of a right diaphragmatic
hernia was established in the coronal view of CT, and emergency surgery was
performed. A dilated loop of small intestine was seen in the right thoracic
cavity, which was strangulated by the 2-cm defect in the diaphragm. Primary
closure of the diaphragm was performed. Approximately 80 cm of the terminal ileum
showed obvious ischemic changes, and it was cut and reconstructed.
Postoperatively, the patient made an uneventful recovery and was discharged on
the 15th postoperative day. A histological examination of the specimen of the
diaphragm around the hernia orifice showed the presence of a small cystiform
glandular system with hemorrhage and congestion. These findings indicated that
heterotopic endometriosis was present in the diaphragm. This report describes the
first known case of right diaphragmatic hernia secondary to heterotopic
endometriosis in a patient with Chilaiditi syndrome. The clinical course and
management of affected patients and a literature review of these three unusual
conditions are discussed.
PMID- 25115926
TI - Role of the water-metal ion bridge in mediating interactions between quinolones
and Escherichia coli topoisomerase IV.
AB - Although quinolones have been in clinical use for decades, the mechanism
underlying drug activity and resistance has remained elusive. However, recent
studies indicate that clinically relevant quinolones interact with Bacillus
anthracis (Gram-positive) topoisomerase IV through a critical water-metal ion
bridge and that the most common quinolone resistance mutations decrease drug
activity by disrupting this bridge. As a first step toward determining whether
the water-metal ion bridge is a general mechanism of quinolone-topoisomerase
interaction, we characterized drug interactions with wild-type Escherichia coli
(Gram-negative) topoisomerase IV and a series of ParC enzymes with mutations
(S80L, S80I, S80F, and E84K) in the predicted bridge-anchoring residues. Results
strongly suggest that the water-metal ion bridge is essential for quinolone
activity against E. coli topoisomerase IV. Although the bridge represents a
common and critical mechanism that underlies broad-spectrum quinolone function,
it appears to play different roles in B. anthracis and E. coli topoisomerase IV.
The water-metal ion bridge is the most important binding contact of clinically
relevant quinolones with the Gram-positive enzyme. However, it primarily acts to
properly align clinically relevant quinolones with E. coli topoisomerase IV.
Finally, even though ciprofloxacin is unable to increase levels of DNA cleavage
mediated by several of the Ser80 and Glu84 mutant E. coli enzymes, the drug still
retains the ability to inhibit the overall catalytic activity of these
topoisomerase IV proteins. Inhibition parallels drug binding, suggesting that the
presence of the drug in the active site is sufficient to diminish DNA relaxation
rates.
PMID- 25115930
TI - Comment on "clinical course and angiographic changes of spontaneous isolated
superior mesenteric artery dissection after conservative treatment".
PMID- 25115929
TI - Intraoperative dissemination during gastrectomy for gastric cancer associated
with serosal invasion.
AB - PURPOSE: Free cancer cells shed from the serosal surface of gastric cancer result
in peritoneal dissemination. The aim of this study was to clarify the extent of
tumor cell implantation due to surgical manipulation during gastrectomy. METHODS:
The participants comprised 34 patients who underwent curative gastrectomy for
gastric cancer with macroscopic serosal invasion. Two types of cytology were
obtained from each patient: (1) cytology from the wound dressing material that
covered the serosal invasion area during the operation (Covering Cy), and (2)
cytology of the intraperitoneal wash samples (Lavage Cy). RESULT: Thirteen
patients showed no serosal invasion histopathologically, and all of these
patients had negative results for both Lavage Cy and Covering Cy. Among the 21
patients with histopathologically confirmed serosal invasion, six had positive
results for both Lavage Cy and Covering Cy, three showed positive findings for
Covering Cy alone, one had positive Lavage Cy alone and 11 patients had negative
results for both Lavage Cy and Covering Cy. Disseminated recurrence developed in
10 patients. Seven of the nine patients with positive Covering Cy developed
disseminated recurrence, compared to three of 12 patients with negative Covering
Cy. Positive Covering Cy findings were significantly associated with disseminated
recurrence (p < 0.05). CONCLUSION: We demonstrated that the intraoperative
dissemination of gastric cancer can occur during gastrectomy.
PMID- 25115933
TI - Spatio-spectral structures in high-order harmonic beams generated with Terawatt
10-fs pulses.
AB - A large international effort is nowadays devoted to increase the energy of the
extreme ultraviolet pulses by using high-peak power ultrashort fundamental pulses
(Terawatt level). Using such fundamental pulses brings specific constraints that
need to be addressed. Here we study high-order harmonic generation in gases with
10 fs pulses at Terawatt peak power and demonstrate that extreme ultraviolet
beams can be highly structured and complex in various conditions. We use a single
shot spatially resolved spectral detection and demonstrate direct observation of
the spatio-temporal coupling occurring in the generating medium. Clear and
reproducible complex spatio-spectral structures are observed in the far field.
Similar structures are reproduced with simulations and we show that they are
intimately associated to the high nonlinearity of high-order harmonic generation.
Those findings are of prime importance for the generation of high-energy
attosecond pulses and reveal important issues for their applications.
PMID- 25115934
TI - Coronary artery compression three months after transcatheter pulmonary valve
implantation.
AB - We report a case of a 29-year-old man who developed exercised-induced myocardial
infarction 3 months post Melody valve implantation. We introduce the concept of
ruling out dynamic coronary artery compression by simulating transcatheter
pulmonary valve implant while increasing cardiac output and thus aortic
dimensions in the catheterization laboratory. (c) 2014 Wiley Periodicals, Inc.
PMID- 25115932
TI - EEG source connectivity analysis: from dense array recordings to brain networks.
AB - The recent past years have seen a noticeable increase of interest for
electroencephalography (EEG) to analyze functional connectivity through brain
sources reconstructed from scalp signals. Although considerable advances have
been done both on the recording and analysis of EEG signals, a number of
methodological questions are still open regarding the optimal way to process the
data in order to identify brain networks. In this paper, we analyze the impact of
three factors that intervene in this processing: i) the number of scalp
electrodes, ii) the combination between the algorithm used to solve the EEG
inverse problem and the algorithm used to measure the functional connectivity and
iii) the frequency bands retained to estimate the functional connectivity among
neocortical sources. Using High-Resolution (hr) EEG recordings in healthy
volunteers, we evaluated these factors on evoked responses during picture
recognition and naming task. The main reason for selection this task is that a
solid literature background is available about involved brain networks (ground
truth). From this a priori information, we propose a performance criterion based
on the number of connections identified in the regions of interest (ROI) that
belong to potentially activated networks. Our results show that the three studied
factors have a dramatic impact on the final result (the identified network in the
source space) as strong discrepancies were evidenced depending on the methods
used. They also suggest that the combination of weighted Minimum Norm Estimator
(wMNE) and the Phase Synchronization (PS) methods applied on High-Resolution EEG
in beta/gamma bands provides the best performance in term of topological distance
between the identified network and the expected network in the above-mentioned
cognitive task.
PMID- 25115935
TI - Acute adiponectin delivery is cardioprotective in the aged female rat heart.
AB - AIM: The aged, post-menopausal female heart is characterized by reduced ischemic
tolerance, and few therapies currently exist to limit ischemic damage.
Adiponectin (APN), a cytokine produced in adipose tissue, limits infarct size and
improves functional recovery after ischemia/reperfusion injury in adult hearts.
The aim of the present study was to extend these previous studies and determine
the cardioprotective efficacy of APN treatment in aged female rats. METHODS:
Hearts were isolated from adult (age 6-7 months; n = 10), aged (age 23 months; n
= 14) and aged ovariectomized (n = 10) female rats, and subjected to
ischemia/reperfusion injury. On ischemia, hearts were infused with 9 MUg of APN
or vehicle. Adiponectin receptor 1, adiponectin receptor 2 and adenosine
monophosphate-dependent kinase (AMPK) were assessed by western blotting, tumor
necrosis factor-alpha and nicotinamide adenine dinucleotide phosphate oxidase
levels by real time polymerase chain reaction. Non-reducing western blotting for
APN multimers in visceral adipose was also carried out. RESULTS: APN infusion
successfully improved post-ischemic left ventricular developed pressure (~10-15%)
and attenuated the rise in end diastolic pressure in all groups (P < 0.05). With
ischemia/reperfusion injury, phospho-AMPK increased in all groups with additive
effects of APN on increasing phospho-AMPK abundance in aged ovary-intact female
rats only (P < 0.001). Age-associated increases in pre-ischemic tumor necrosis
factor-alpha mRNA were unaffected by APN, whereas nicotinamide adenine
dinucleotide phosphate oxidase 2 mRNA levels were attenuated by APN in adult and
aged ovariectomized female rats. An age-associated decrease in cardiac
adiponectin receptor 2 was observed in conjunction with elevated high molecular
weight APN in adipose. CONCLUSIONS: The present data suggest that APN might be a
relevant therapy for protecting the aging female heart, albeit through divergent
mechanisms that are likely influenced by age-associated estrogen availability.
PMID- 25115936
TI - No abnormal hexanucleotide repeat expansion of C9ORF72 in Japanese schizophrenia
patients.
AB - Abnormal hexanucleotide repeat expansion of C9ORF72 is known to cause
neurodegenerative disorders such as frontotemporal dementia. Additionally,
patients with psychotic symptoms are more likely to have abnormal hexanucleotide
repeat expansion than are patients without them. We investigated the
hexanucleotide repeat sizes of C9ORF72 in 466 Japanese schizophrenia patients. We
found no abnormal hexanucleotide repeat expansion. In conclusion, C9ORF72 may not
be responsible for schizophrenia susceptibility in the Japanese population.
PMID- 25115938
TI - Religious pro-sociality? Experimental evidence from a sample of 766 Spaniards.
AB - This study explores the relationship between several personal religion-related
variables and social behaviour, using three paradigmatic economic games: the
dictator (DG), ultimatum (UG), and trust (TG) games. A large carefully designed
sample of the urban adult population in Granada (Spain) is employed (N = 766).
From participants' decisions in these games we obtain measures of altruism,
bargaining behaviour and sense of fairness/equality, trust, and positive
reciprocity. Three dimensions of religiosity are examined: (i) religious
denomination; (ii) intensity of religiosity, measured by active participation at
church services; and (iii) conversion out into a different denomination than the
one raised in. The major results are: (i) individuals with "no religion" made
decisions closer to rational selfish behaviour in the DG and the UG compared to
those who affiliate with a "standard" religious denomination; (ii) among
Catholics, intensity of religiosity is the key variable that affects social
behaviour insofar as religiously-active individuals are generally more pro-social
than non-active ones; and (iii) the religion raised in seems to have no effect on
pro-sociality, beyond the effect of the current measures of religiosity.
Importantly, behaviour in the TG is not predicted by any of the religion-related
variables we analyse. While the results partially support the notion of religious
pro-sociality, on the other hand, they also highlight the importance of closely
examining the multidimensional nature of both religiosity and pro-social
behaviour.
PMID- 25115937
TI - Phosphorylation at Y1065 in vinculin mediates actin bundling, cell spreading, and
mechanical responses to force.
AB - Vinculin is an essential structural adaptor protein that localizes to sites of
adhesion and is involved in a number of cell processes including adhesion,
spreading, motility, force transduction, and cell survival. The C-terminal
vinculin tail domain (Vt) contains the necessary structural components to bind
and cross-link actin filaments. Actin binding to Vt induces a conformational
change that promotes dimerization through the C-terminal hairpin of Vt and
enables actin filament cross-linking. Here we show that Src phosphorylation of
Y1065 within the C-terminal hairpin regulates Vt-mediated actin bundling and
provide a detailed characterization of Y1065 mutations. Furthermore, we show that
phosphorylation at Y1065 plays a role in cell spreading and the response to the
application of mechanical force.
PMID- 25115941
TI - Alcohol should carry similar warnings to tobacco, MPs say.
PMID- 25115940
TI - SMBE Satellite meeting on reticulated microbial evolution 2014--meeting report.
PMID- 25115939
TI - Increased risk of dementia in patients exposed to nitrogen dioxide and carbon
monoxide: a population-based retrospective cohort study.
AB - BACKGROUND: The air pollution caused by vehicular emissions is associated with
cognitive decline. However, the associations between the levels of nitrogen
dioxide (NO2) and carbon monoxide (CO) exposure and dementia remain poorly
defined and have been addressed in only a few previous studies. MATERIALS AND
METHODS: In this study, we obtained data on 29547 people from the National Health
Insurance Research Database (NHIRD) of Taiwan, including data on 1720 patients
diagnosed with dementia between 2000 and 2010, and we evaluated the risk of
dementia among four levels of air pollutant. Detailed data on daily air pollution
were available from January 1, 1998 to December 31, 2010. Yearly average
concentrations of pollutants were calculated from the baseline to the date of
dementia occurrence, withdrawal of patients, or the end of the study, and these
data were categorized into quartiles, with Q1 being the lowest level and Q4 being
the highest. RESULTS: In the case of NO2, the adjusted hazard ratios (HRs) of
dementia for all participants in Q2, Q3, and Q4 compared to Q1 were 1.10 (95%
confidence interval (CI), 0.96-1.26), 1.01 (95% CI, 0.87-1.17), and 1.54 (95% CI,
1.34-1.77), and in the case of CO, the adjusted HRs were 1.07 (95% CI, 0.92
1.25), 1.37 (95% CI, 1.19-1.58), and 1.61 (95% CI, 1.39-1.85). CONCLUSION: The
results of this large retrospective, population-based study indicate that
exposure to NO2 and CO is associated with an increased risk of dementia in the
Taiwanese population.
PMID- 25115942
TI - Achieving solar overall water splitting with hybrid photosystems of photosystem
II and artificial photocatalysts.
AB - Solar overall water splitting is a promising sustainable approach for solar-to
chemical energy conversion, which harnesses solar irradiation to oxidize water to
oxygen and reduce the protons to hydrogen. The water oxidation step is vital but
difficult to achieve through inorganic photocatalysis. However, nature offers an
efficient light-driven water-oxidizing enzyme, photosystem II (PSII). Here we
report an overall water splitting natural-artificial hybrid system, in which the
plant PSII and inorganic photocatalysts (for example, Ru/SrTiO3:Rh), coupled with
an inorganic electron shuttle [Fe(CN)6(3-)/Fe(CN)6(4-)], are integrated and
dispersed in aqueous solutions. The activity of this hybrid photosystem reaches
to around 2,489 mol H2 (mol PSII)(-1) h(-1) under visible light irradiation, and
solar overall water splitting is also achieved under solar irradiation outdoors.
The optical imaging shows that the hybrid photosystems are constructed through
the self-assembly of PSII adhered onto the inorganic photocatalyst surface. Our
work may provide a prototype of natural-artificial hybrids for developing
autonomous solar water splitting system.
PMID- 25115944
TI - Serial intravascular ultrasound analysis of complex bifurcation coronary lesions
treated with the Tryton Bifurcation Stent in conjunction with an everolimus
eluting stent: IUVANT (Intravascular Ultrasound Evaluation of Tryton Stent)
study.
AB - OBJECTIVES: To characterize the treatment of complex bifurcation lesions (BL)
with the Tryton Bifurcation Stent (TBS) paired with an everolimus-eluting stent
(EES). BACKGROUND: Complex BL are associated with higher procedural complications
and poorer long-term outcomes. The TBS is a dedicated side-branch (SB) stent
designed to be used in conjunction with a standard drug-eluting stent. METHODS:
Prospectively identified, consecutive patients underwent TBS+EES stenting of BL
using a protocol which included TBS postdilation and simultaneous final kissing
balloon inflations (FKBI). All lesions were systematically evaluated with
coronary angiography and IVUS, obtained at procedure completion and at 9 months,
and were assessed by independent core laboratories. RESULTS: Thirty-three BL were
treated in 32 patients presenting primarily (87.5%) with stable angina and
complex BL with angiographic apparent disease in the main vessel (MV) and SB in
87.9% and 75% by site and core evaluation, respectively. Procedural success was
100% and high postprocedure percent stent expansion (MV 96 [93, 109]%, SB 88 [77,
100]%, carina MV 135 [99, 166]%, carina SB 116 [91, 130]%) was demonstrated by
IVUS. At 9-month angiographic follow-up (n = 28 patients), one MV in-segment
restenosis and one SB in-stent restenosis were observed. SB in-stent late lumen
loss was 0.41 +/- 0.27 mm. IVUS assessment revealed the absence of stent recoil;
percent carinal neointimal hyperplasia (NIH) was 1.8 [0.0,11.2]% in MV and 15.0
[6.7,23.5]% in SB, with NIH volume obstruction of 2.0 [0.7,4.3]% in MV and 14.2
[7.5,29.6]% in SB. CONCLUSIONS: Stenting of complex BL with the TBS+EES provides
high acute success with sustained clinical, angiographic, and IVUS results at 9
months. These excellent results are likely due to the extent of stent expansion
at the carina.
PMID- 25115946
TI - Complete genome sequence of virulent bacteriophage SHOU24, which infects
foodborne pathogenic Vibrio parahaemolyticus.
AB - A novel lytic Vibrio parahaemolyticus phage (SHOU24) belonging to the family
Siphoviridae was isolated from aquatic market sewage. The phage is only able to
infect V. parahaemolyticus containing a tdh gene. SHOU24 has a linear genome of
77,837 bp with a G+C content of 46.0 %. In total, 88 predicted proteins have
homologues in databases, and the majority of the core genes share high sequence
similarity with genes from unrelated viruses and bacteria. Genes related to
lysogeny and host lysis were not detected. However, the detection method, the
results of a one-step growth experiment and analysis using the Phage
Classification Tool Set (PHACTS) indicate that SHOU24 is lytic. A bioinformatics
analysis showed that SHOU24 is not closely related to other Vibrio phages.
PMID- 25115943
TI - Complex communities of small protists and unexpected occurrence of typical marine
lineages in shallow freshwater systems.
AB - Although inland water bodies are more heterogeneous and sensitive to
environmental variation than oceans, the diversity of small protists in these
ecosystems is much less well known. Some molecular surveys of lakes exist, but
little information is available from smaller, shallower and often ephemeral
freshwater systems, despite their global distribution and ecological importance.
We carried out a comparative study based on massive pyrosequencing of amplified
18S rRNA gene fragments of protists in the 0.2-5 MUm size range in one brook and
four shallow ponds located in the Natural Regional Park of the Chevreuse Valley,
France. Our study revealed a wide diversity of small protists, with 812
stringently defined operational taxonomic units (OTUs) belonging to the
recognized eukaryotic supergroups (SAR--Stramenopiles, Alveolata, Rhizaria-
Archaeplastida, Excavata, Amoebozoa, Opisthokonta) and to groups of unresolved
phylogenetic position (Cryptophyta, Haptophyta, Centrohelida, Katablepharida,
Telonemida, Apusozoa). Some OTUs represented deep-branching lineages
(Cryptomycota, Aphelida, Colpodellida, Tremulida, clade-10 Cercozoa, HAP-1
Haptophyta). We identified several lineages previously thought to be marine
including, in addition to MAST-2 and MAST-12, already detected in freshwater,
MAST-3 and possibly MAST-6. Protist community structures were different in the
five ecosystems. These differences did not correlate with geographical distances,
but seemed to be influenced by environmental parameters.
PMID- 25115948
TI - An evaluation of e-prescribing at a national level.
AB - OBJECTIVE: The aim of the article is to describe the process of implementing the
Estonian national second generation electronic prescription service (e
prescription) and determine if the objectives set by the Estonian government were
fulfilled. MATERIALS AND METHODS: The study presents an analysis of both
retrospective and current data in the evaluation phase of a design research
project. Sources include, among others, publicly available documents and previous
evaluation studies. RESULTS: According to all of the major stakeholders, the
Estonian e-prescription service has very high usability and user satisfaction
scores have been high. There is only little empirical evidence available to
confirm if the benefits aimed for in the creation of the service were achieved.
From a public administration viewpoint, the implementation of e-prescription has
led to potential efficiency gains. CONCLUSION: The Estonian second-generation e
prescription system is widely used by citizens, healthcare providers and
administrators alike. However, there are gaps in measuring the impact of the
service, especially with respect to time savings and enhanced healthcare quality.
Additional functionalities will be key drivers in creating benefits for all
stakeholders. Future nationwide e-health services should have a more rigorous
evaluation process carried out during the design and implementation stages.
PMID- 25115947
TI - Socioeconomic Adversity and Women's Sleep: Stress and Chaos as Mediators.
AB - We examined income-to-needs ratio, perceived economic well-being, and education
and their relations with European and African American women's sleep (n = 219).
Sleep was examined through actigraphy and self-reports. Income-to-needs ratio was
related to sleep minutes. Perceived economic well-being and education were
associated with subjective sleep problems. Perceived stress mediated relations
between both income-to-needs ratio and economic well-being and subjective sleep
problems. Chaos emerged as a mediator linking income-to-needs ratio and
subjective sleep problems. African American women had fewer sleep minutes and
lower sleep efficiency than European Americans, and more robust relations between
economic well-being and stress was observed for European Americans. Findings
highlight the importance of economic adversity for women's sleep and explicate
some pathways of risk.
PMID- 25115949
TI - Saliva viscosity as a potential risk factor for oral malodor.
AB - OBJECTIVES: The objective of this study was to assess whether saliva viscosity,
measured by a viscometer, was a predictor of oral malodor. MATERIALS AND METHODS:
The subjects were 617 patients who visited an oral malodor clinic. The
organoleptic test (OT) was used for diagnosis of oral malodor. An oral
examination assessed the numbers of teeth present and decayed teeth as well as
the presence or absence of dentures. Further, periodontal pocket depths (PD),
gingival bleeding, dental plaque and tongue coating were investigated.
Unstimulated saliva were collected for 5 min. Saliva viscosity was measured with
a viscometer. Logistic regression analysis with oral malodor status by OT as a
dependent variable was performed. Possible confounders including age, gender,
number of teeth present, number of decayed teeth, number of teeth with PD >= 4
mm, number of teeth with bleeding on probing, presence or absence of dentures,
plaque index, area of tongue coating, saliva flow rate, saliva pH and saliva
viscosity were used as independent variables. RESULTS: Saliva viscosity (p =
0.047) along with the number of teeth with PD >=4 mm (p = 0.001), plaque index (p
= 0.037) and area of tongue coating (p < 0.001) were significant variables for
oral malodor. Subjects with a higher number of teeth with PD >= 4 mm (OR = 1.32),
plaque index (OR = 2.13), area of tongue coating (OR = 3.17) and saliva viscosity
(OR = 1.10) were more likely to have oral malodor compared to those with lower
values. CONCLUSIONS: The results suggested that high saliva viscosity could be a
potential risk factor for oral malodor.
PMID- 25115950
TI - An assessment of the usefulness of Kinesiograph as an aid in the diagnosis of
TMD: a review of Manfredini et al.'s studies.
AB - AIM: Performing a literature review of publications by Dr. Manfredini et al.
related to their temporomandibular joint (TMJ) injection therapy outcome with
conclusions on the clinical utility of computerized measurement devices used in
the management of temporomandibular disorders (TMDs). In addition, reviewing
their published opinion on an occlusion: TMD versus a biopsychosocial paradigm
for TMD. Manfredini et al. authored an article published in the Journal of the
American Dental Association (JADA) 2013, "An Assessment of the usefulness of jaw
kinesiography in monitoring temporomandibular disorders," the most recent of 12
articles. In all studies, subjects received TMJ injections with an objective
measurement outcome criterion; increased maximum mouth opening (MMO) and
subjective symptom improvement of pain and chewing function. In the 2013 JADA
article, the Mandibular Kinesiograph, referred to as KG, measured MMO before and
after therapy. In 11 prior articles, all subject groups with limited mouth
opening exhibited very significant increased MMO post-treatment, documenting
treatment success using the same 2013 protocol. The 2013 study showed a 1.1 mm
improved MMO, described as insignificant. The authors did not critique or explain
the aberrant, skewed 2013 outcome data contrasted with their prior studies, which
showed overwhelmingly significant increased MMO. Instead, they concluded that the
MMO recording device was clinically useless. This motivated a literature review
of the authors' TMD publications. CONCLUSION: The publications by Manfredini et
al. recognized proponents of the psychosocial model of TMD, including the 2013
article, appear to be part of a campaign denying an occlusion: TMD relationship
and disparaging the specific computerized measurement devices and the dentists
using them in the management of their TMD patients using neuromuscular occlusion
dental treatment.
PMID- 25115951
TI - Thermodynamic consistencies and anomalies among end-member silicate garnets.
AB - Materials with the garnet crystal structure include silicate minerals of
importance both in geology, on account of their use in geothermobarometry, and
industrially as abrasives. As a consequence of the former, there is considerable
published thermodynamic information concerning them. We here examine this
thermodynamic information for end-member silicate garnets (some of which are
synthetic since not all occur in nature) for consistencies and anomalies, using
thermodynamic relations between thermodynamic properties that we have established
over recent years. The principal properties of interest are formula volume, heat
capacity, entropy, formation enthalpy (from which the Gibbs energy may be
obtained), and isothermal compressibility. A significant observation is that the
ambient-temperature heat capacities of the silicate garnets are rather similar,
whereas their ambient-temperature entropies are roughly proportional to their
formula volumes. Evaluation of their Debye temperatures implies that their
vibrational contributions to heat capacity are fully excited at ambient
temperatures. The relatively small isothermal compressibilities of these garnets
is related to the rigidity of their constituent silicate tetrahedra. We here
establish additive single-ion values for each of the thermodynamic properties,
which may be applied in estimating corresponding values for related materials.
PMID- 25115952
TI - The stigmatisation of abortion: a qualitative analysis of print media in Great
Britain in 2010.
AB - The media play a significant part in shaping public perceptions of health issues,
and abortion attracts continued media interest. Detailed examination of media
constructions of abortion may help to identify emerging public discourse.
Qualitative content analysis was used to examine if and how the print media in
contributes to the stigmatisation of abortion. Articles from seven British and
five Scottish national newspapers from 2010 were analysed for overall framings of
abortion and emergent themes, including potentially stigmatising discursive
constructs and language. Abortion was found to be presented using predominantly
negative language and discursive associations as 'risky', and in association with
other 'discredited' social practices. Key perspectives were found to be absent or
marginalised, including those of women who have sought abortion. Few articles
framed abortion as a positive and legitimate choice. Negative media
representations of abortion contribute to the stigmatisation of the procedure and
of women who have it, and reflect a discrediting of women's reproductive decision
making. There is a need to challenge the notion that abortion stigma is
inevitable, and to encourage positive framings of abortion in the media and other
public discourse.
PMID- 25115953
TI - Clonal structure, seed set, and self-pollination rate in mass-flowering bamboo
species during off-year flowering events.
AB - Bamboos are typical examples of highly synchronized semelparous species. Their
mass-flowering events occur at supra-annual intervals but they sometimes flower
on a small scale in off-years. If some bamboo ramets (culms) of a genet flower
and die in off-years, whereas other culms of the same genet do not flower
synchronously, the genet can still survive blooming in an off-year and could
participate in the next mass-flowering event. At genet level, the effect might be
similar to that achieved by synchronously reproducing iteroparous plants. In
addition, if multiple genets flower simultaneously in off-years, cross
pollination will be promoted. However, it is not known whether all the culms in a
genet flower synchronously and whether multiple genets flower in off-years. We
determined the clonal structure of three temperate dwarf bamboo species, i.e.,
Sasa senanensis, S. kurilensis, and S. palmata, at 24 off-year flowering sites
and the surrounding areas in northern Japan using seven microsatellite markers.
We also estimated seed set at seven of the sites and self-pollination rates at
five sites to determine off-year reproductive success. Next, we investigated
whether seed sets at the culm level were related to flowering area and/or number
of flowering genets, using generalized linear mixed-effect models (GLMMs).
Multiple genets flowered at 9/24 flowering sites. We found that 40/96 of the
genets identified had some flowering culms. Non-flowering culms were present in
24/40 flowering genets. Seed set was in the range 2.2%-12.5% and the self
pollination rate was 96.3%. In the best GLMM, seed set increased with flowering
area. Seeds were produced in off-years, but cross-pollination was rare in off
years. We suggest that some dwarf bamboos may exhibit iteroparity or imperfectly
synchronized semelparity at the genet level, a characteristic similar to that of
other reproductively synchronous plants. We also found synchronous flowering of a
few genets even in off-years.
PMID- 25115957
TI - Retrospective non-uniform illumination correction techniques in images of
tuberculosis.
AB - Image pre-processing is highly significant in automated analysis of microscopy
images. In this work, non-uniform illumination correction has been attempted
using the surface fitting method (SFM), multiple regression method (MRM), and
bidirectional empirical mode decomposition (BEMD) in digital microscopy images of
tuberculosis (TB). The sputum smear positive and negative images recorded under a
standard image acquisition protocol were subjected to illumination correction
techniques and evaluated by error and statistical measures. Results show that SFM
performs more efficiently than MRM or BEMD. The SFM produced sharp images of TB
bacilli with better contrast. To further validate the results, multifractal
analysis was performed that showed distinct variation before and after
implementation of illumination correction by SFM. Results demonstrate that after
illumination correction, there is a 26% increase in the number of bacilli, which
aids in classification of the TB images into positive and negative, as TB
positivity depends on the count of bacilli.
PMID- 25115958
TI - Energy transport and coherence properties of acoustic phonons generated by
optical excitation of a quantum dot.
AB - The energy transport of acoustic phonons generated by the optical excitation of a
quantum dot as well as the coherence properties of these phonons are studied
theoretically both for the case of a pulsed excitation and for a continuous wave
(CW) excitation switched on instantaneously. For a pulsed excitation, depending
on pulse area and pulse duration, a finite number of phonon wave packets is
emitted, while for the case of a CW excitation a sequence of wave packets with
decreasing amplitude is generated after the excitation has been switched on. We
show that the energy flow associated with the generated phonons is partly related
to coherent phonon oscillations and partly to incoherent phonon emission. The
efficiency of the energy transfer to the phonons and the details of the energy
flow depend strongly and in a non-monotonic way on the Rabi frequency exhibiting
a resonance behavior. However, in the case of CW excitation it turns out that the
total energy transferred to the phonons is directly linked in a monotonic way to
the Rabi frequency.
PMID- 25115960
TI - [Anterior resection syndrome and quality of life in rectal cancer patients].
PMID- 25115959
TI - [Femoroacetabular impingement in athletes: pathology, diagnostics and operative
therapy options].
AB - Femoroacetabular impingement (FAI) and its therapy has gained importance in the
last decade and several studies could show that if untreated it may lead to
osteoarthritis of the hip joint. In this article an overview of the pathology of
FAI, the diagnosis and treatment options are presented. A closer look is taken at
the treatment of elite athletes regarding the different techniques. The first own
clinical and radiological results of 91 patients treated by the arthroscopically
assisted anterior mini-open approach are presented with very good results and
significant postoperative improvement regarding the hip injury and osteoarthritis
outcome score (HOOS), the Western Ontario and McMasters University (WOMAC)
osteoarthritis index and the University of California Los Angeles (UCLA) activity
score, as well as alpha angle correction. This technique which is poorly
represented in the literature can be used as a treatment option for FAI. The
rehabilitation program is comparable to hip arthroscopy.
PMID- 25115961
TI - Evolution of external genitalia: insights from reptilian development.
AB - External genitalia are found in each of the major clades of amniotes. The phallus
is an intromittent organ that functions to deliver sperm into the female
reproductive tract for internal fertilization. The cellular and molecular genetic
mechanisms of external genital development have begun to be elucidated from
studies of the mouse genital tubercle, an embryonic appendage adjacent to the
cloaca that is the precursor of the penis and clitoris. Progress in this area has
improved our understanding of genitourinary malformations, which are among the
most common birth defects in humans, and created new opportunities for
comparative studies of other taxa. External genitalia evolve rapidly, which has
led to a striking diversity of anatomical forms. Within the past year, studies of
external genital development in non-mammalian amniotes, including birds, lizards,
snakes, alligators, and turtles, have begun to shed light on the molecular and
morphogenetic mechanisms underlying the diversification of phallus morphology.
Here, we review recent progress in the comparative developmental biology of
external genitalia and discuss the implications of this work for understanding
external genital evolution. We address the question of the deep homology (shared
common ancestry) of genital structures and of developmental mechanisms, and
identify new areas of investigation that can be pursued by taking a comparative
approach to studying development of the external genitalia. We propose an
evolutionary interpretation of hypospadias, a congenital malformation of the
urethra, and discuss how investigations of non-mammalian species can provide
novel perspectives on human pathologies.
PMID- 25115963
TI - Biocatalytic coatings for air pollution control: a proof of concept study on VOC
biodegradation.
AB - Although biofilm-based biotechnologies exhibit a large potential as solutions for
off-gas treatment, the high water content of biofilms often causes pollutant mass
transfer limitations, which ultimately limit their widespread application. The
present study reports on the proof of concept of the applicability of bioactive
latex coatings for air pollution control. Toluene vapors served as a model
volatile organic compound (VOC). The results showed that Pseudomonas putida F1
cells could be successfully entrapped in nanoporous latex coatings while
preserving their toluene degradation activity. Bioactive latex coatings exhibited
toluene specific biodegradation rates 10 times higher than agarose-based
biofilms, because the thin coatings were less subject to diffusional mass
transfer limitations. Drying and pollutant starvation were identified as key
factors inducing a gradual deterioration of the biodegradation capacity in these
innovative coatings. This study constitutes the first application of bioactive
latex coatings for VOC abatement. These coatings could become promising means for
air pollution control.
PMID- 25115962
TI - Failed stabilization for long-term potentiation in the auditory cortex of FMR1
knockout mice.
AB - Fragile X syndrome is a developmental disorder that affects sensory systems. A
null mutation of the Fragile X Mental Retardation protein 1 (Fmr1) gene in mice
has varied effects on developmental plasticity in different sensory systems,
including normal barrel cortical plasticity, altered ocular dominance plasticity
and grossly impaired auditory frequency map plasticity. The mutation also has
different effects on long-term synaptic plasticity in somatosensory and visual
cortical neurons, providing insights on how it may differentially affect the
sensory systems. Here we present evidence that long-term potentiation (LTP) is
impaired in the developing auditory cortex of the Fmr1 knockout (KO) mice. This
impairment of synaptic plasticity is consistent with impaired frequency map
plasticity in the Fmr1 KO mouse. Together, these results suggest a potential role
of LTP in sensory map plasticity during early sensory development.
PMID- 25115964
TI - Revealing the dark side of a bright exciton-polariton condensate.
AB - Condensation of bosons causes spectacular phenomena such as superfluidity or
superconductivity. Understanding the nature of the condensed particles is crucial
for active control of such quantum phases. Fascinating possibilities emerge from
condensates of light-matter-coupled excitations, such as exciton-polaritons,
photons hybridized with hydrogen-like bound electron-hole pairs. So far, only the
photon component has been resolved, while even the mere existence of excitons in
the condensed regime has been challenged. Here we trace the matter component of
polariton condensates by monitoring intra-excitonic terahertz transitions. We
study how a reservoir of optically dark excitons forms and feeds the degenerate
state. Unlike atomic gases, the atom-like transition in excitons is dramatically
renormalized on macroscopic ground state population. Our results establish
fundamental differences between polariton condensation and photon lasing and open
possibilities for coherent control of condensates.
PMID- 25115965
TI - Learning a weighted meta-sample based parameter free sparse representation
classification for microarray data.
AB - Sparse representation classification (SRC) is one of the most promising
classification methods for supervised learning. This method can effectively
exploit discriminating information by introducing a [Symbol: see text]1
regularization terms to the data. With the desirable property of sparisty, SRC is
robust to both noise and outliers. In this study, we propose a weighted meta
sample based non-parametric sparse representation classification method for the
accurate identification of tumor subtype. The proposed method includes three
steps. First, we extract the weighted meta-samples for each sub class from raw
data, and the rationality of the weighting strategy is proven mathematically.
Second, sparse representation coefficients can be obtained by [Symnbol: see
text]1 regularization of underdetermined linear equations. Thus, data dependent
sparsity can be adaptively tuned. A simple characteristic function is eventually
utilized to achieve classification. Asymptotic time complexity analysis is
applied to our method. Compared with some state-of-the-art classifiers, the
proposed method has lower time complexity and more flexibility. Experiments on
eight samples of publicly available gene expression profile data show the
effectiveness of the proposed method.
PMID- 25115967
TI - Automating lexical cross-mapping of ICNP to SNOMED CT.
AB - OBJECTIVES: The purpose of this study was to examine the feasibility of
automating lexical cross-mapping of a logic-based nursing terminology (ICNP) to
SNOMED CT using the Unified Medical Language System (UMLS) maintained by the U.S.
National Library of Medicine. METHODS: A two-stage approach included patterns
identification, and application and evaluation of an automated term matching
procedure. The performance of the automated procedure was evaluated using a test
set against a gold standard (i.e. concept equivalency table) created
independently by terminology experts. RESULTS: There were lexical similarities
between ICNP diagnostic concepts and SNOMED CT. The automated term matching
procedure was reliable as presented in recall of 65%, precision of 79%, accuracy
of 82%, F-measure of 0.71 and the area under the receiver operating
characteristics (ROC) curve of 0.78 (95% CI 0.73-0.83). When the automated
procedure was not able to retrieve lexically matched concepts, it was also
unlikely for terminology experts to identify a matched SNOMED CT concept.
CONCLUSIONS: Although further research is warranted to enhance the automated
matching procedure, the combination of cross-maps from UMLS and the automated
procedure is useful to generate candidate mappings and thus, assist ongoing
maintenance of mappings which is a significant burden to terminology developers.
PMID- 25115966
TI - Sex-based differences in bleeding and long term adverse events after percutaneous
coronary intervention for acute myocardial infarction: three year results from
the HORIZONS-AMI trial.
AB - BACKGROUND: Studies have shown sex-based disparities in ST-segment elevation
myocardial infarction (STEMI) management and prognosis. We sought to compare
women and men undergoing primary percutaneous coronary intervention (PCI) for
STEMI in a large, prospective, contemporary context. METHODS: The Harmonizing
Outcomes with Revascularization and Stents in Acute Myocardial Infarction
(HORIZONS-AMI) trial randomized 3,602 patients (23.4% women and 76.6% men) with
STEMI presenting within 12 hr of onset of symptoms to bivalirudin or heparin plus
glycoprotein IIb/IIIa inhibitors and to PCI with drug-eluting or bare metal
stents. RESULTS: Compared with men, women presented later after symptom onset and
were more often treated with medical management alone (6.9% vs. 4.7%; P = 0.01).
Women had significantly higher rates of 3-year major adverse cardiac events
(MACE) and major bleeding. After adjusting for baseline differences, female sex
remained an independent predictor of major bleeding (hazard ratio [HR] 1.81, 95%
confidence interval [CI] 1.41-2.33; P < 0.0001) but not of MACE (HR 1.09; 95% CI
0.91-1.32; P = 0.35). CONCLUSIONS: This study found that women with STEMI are at
increased risk of bleeding as compared to men. While female sex may not directly
contribute to increased risk of MACE, it is, however, associated with the
presence of comorbidities that increase the risk of ischemic events long-term.
Further dedicated studies are needed to confirm these findings and to assess
strategies to optimize both the initial emergent treatment and long-term
management in this high-risk subset. (c) 2014 Wiley Periodicals, Inc.
PMID- 25115968
TI - The global regulator FfSge1 is required for expression of secondary metabolite
gene clusters but not for pathogenicity in Fusarium fujikuroi.
AB - The plant pathogenic fungus Fusarium fujikuroi is the causal agent of bakanae
disease on rice due to its ability to produce gibberellins. Besides these
phytohormones, F. fujikuroi is able to produce several other secondary
metabolites (SMs). Although much progress has been made in the field of secondary
metabolism, the transcriptional regulation of SM biosynthesis is complex and
still incompletely understood. Environmental conditions, global as well as
pathway-specific regulators and chromatin remodelling have been shown to play
major roles. Here, the role of FfSge1, a homologue of the morphological switch
regulators Wor1 and Ryp1 in Candida albicans and Histoplasma capsulatum,
respectively, is explored with emphasis on secondary metabolism. FfSge1 is not
required for formation of conidia and pathogenicity but is involved in vegetative
growth. Transcriptome analysis of the mutant Deltaffsge1 compared with the wild
type, as well as comparative chemical analysis between the wild type, Deltaffsge1
and OE:FfSGE1, revealed that FfSge1 functions as a global activator of secondary
metabolism in F. fujikuroi. Double mutants of FfSGE1 and other SM regulatory
genes brought insights into the hierarchical regulation of secondary metabolism.
In addition, FfSge1 is also required for expression of a yet uncharacterized SM
gene cluster containing a non-canonical non-ribosomal peptide synthetase.
PMID- 25115971
TI - Erratum to: Nephroprotective activities of quercetin with potential relevance to
oxidative stress induced by valproic acid.
PMID- 25115969
TI - What Role Does Sleep Play in Weight Gain in the First Semester of University?
AB - We hypothesized that shorter sleep durations and greater variability in sleep
patterns are associated with weight gain in the first semester of university.
Students (N = 132) completed daily sleep diaries for 9 weeks, completed the MEQ
(chronotype) and CES-D (depressed mood) at week 9, and self-reported
weight/height (weeks 1 & 9). Mean and variability scores were calculated for
sleep duration (TST, TSTv), bedtime (BT, BTv), and wake time (WT, WTv). An
initial hierarchical regression evaluated (block 1) sex, ethnicity; (block 2)
depressed mood, chronotype; (block 3) TST; (block 4) BT, WT; and (block 5; R(2)
change = 0.09, p = 0.005) TSTv, BTv, WTv with weight change. A sex-by-TSTv
interaction was found. A final model showed that ethnicity, TST, TSTv, and BTv
accounted for 31% of the variance in weight change for males; TSTv was the most
significant contributor (R(2) change = 0.21, p < 0.001). Daily variability in
sleep duration contributes to males' weight gain. Further investigation needs to
examine sex-specific outcomes for sleep and weight.
PMID- 25115970
TI - A numerical investigation of the electric and thermal cell kill distributions in
electroporation-based therapies in tissue.
AB - Electroporation-based therapies are powerful biotechnological tools for enhancing
the delivery of exogeneous agents or killing tissue with pulsed electric fields
(PEFs). Electrochemotherapy (ECT) and gene therapy based on gene electrotransfer
(EGT) both use reversible electroporation to deliver chemotherapeutics or plasmid
DNA into cells, respectively. In both ECT and EGT, the goal is to permeabilize
the cell membrane while maintaining high cell viability in order to facilitate
drug or gene transport into the cell cytoplasm and induce a therapeutic response.
Irreversible electroporation (IRE) results in cell kill due to exposure to PEFs
without drugs and is under clinical evaluation for treating otherwise
unresectable tumors. These PEF therapies rely mainly on the electric field
distributions and do not require changes in tissue temperature for their
effectiveness. However, in immediate vicinity of the electrodes the treatment may
results in cell kill due to thermal damage because of the inhomogeneous electric
field distribution and high current density during the electroporation-based
therapies. Therefore, the main objective of this numerical study is to evaluate
the influence of pulse number and electrical conductivity in the predicted cell
kill zone due to irreversible electroporation and thermal damage. Specifically,
we simulated a typical IRE protocol that employs ninety 100-us PEFs. Our results
confirm that it is possible to achieve predominant cell kill due to
electroporation if the PEF parameters are chosen carefully. However, if either
the pulse number and/or the tissue conductivity are too high, there is also
potential to achieve cell kill due to thermal damage in the immediate vicinity of
the electrodes. Therefore, it is critical for physicians to be mindful of
placement of electrodes with respect to critical tissue structures and treatment
parameters in order to maintain the non-thermal benefits of electroporation and
prevent unnecessary damage to surrounding healthy tissue, critical vascular
structures, and/or adjacent organs.
PMID- 25115972
TI - A clinical experience of 'STAMP' plate-guided Bonebridge implantation.
AB - CONCLUSION: The surface template-assisted marker positioning (STAMP) method is
useful for successful BonebridgeTM (BB) implantation on a planned site while
avoiding dangerous positions. OBJECTIVES: To confirm the usefulness of the STAMP
method for the safe operation of BB. METHODS: From a patient's temporal bone CT
data, a guide plate and confirmation plate were generated by the STAMP method.
The guide plate is used to mark the correct place for implantation, while the
confirmation plate lets us know the correct angle and depth of the hole. RESULTS:
With the guide plate, the correct place for BB implantation was easily found. The
hole was made to be an appropriate size with the confirmation plate while
exposing only a small part of sigmoid sinus as simulated. Finally, the BB implant
was successfully placed exactly at the planned site.
PMID- 25115973
TI - Recent development of sandwich assay based on the nanobiotechnologies for
proteins, nucleic acids, small molecules, and ions.
PMID- 25115975
TI - Unhelpful information about adverse drug reactions.
PMID- 25115976
TI - Roughness and morphology of composites: influence of type of material, fluoride
solution, and time.
AB - This study evaluated the effect of fluoride solutions on surface roughness and
morphology of composites in the short and long term. Specimens were randomly
assigned to experimental groups (n=5) according to type of composite (nanofilled,
microhybrid, microfilled) and immersion media (artificial saliva, 0.05% sodium
fluoride solution, Fluordent Reach, Oral-B, and Fluorgard). Roughness was
evaluated at time intervals: T 0 after 24 h in artificial saliva (baseline); T 60
after being in assigned immersion media for 1 min daily over 60 days; and T final
after artificial aging (20,000 thermal cycles, 1,200,000 mechanical loading
cycles, and continuous immersion for 1,825 min). Surface morphology was
qualitatively analyzed by scanning electron microscopy (SEM) at T 60 and T final.
Roughness data were submitted to analysis of variance for mixed repeated
measures, Sidak, and Tukey tests at alpha=0.05. Micro-filled resin showed the
highest roughness values. Fluoride solutions had no influence on roughness.
Higher roughness values were observed after artificial aging. In SEM observations
after the artificial aging, the specimens showed surface degradation,
irrespective of immersion medium or type of composite. Nano-filled resin showed
higher loss of resin matrix and protrusion of filler particles. Roughness was not
influenced by fluoride solutions; however, it is material dependent and increases
over time.
PMID- 25115977
TI - A reversible conversion between a skyrmion and a domain-wall pair in a junction
geometry.
AB - Skyrmions are expected to be a key component of the next-generation of
spintronics: known as 'skyrmionics'. On the other hand, there is a well
established memory device encoded by a sequence of domain walls. Here we show a
conversion is possible between a skyrmion and a domain-wall pair by connecting
wide and narrow nanowires, enabling the information transmission between a
skyrmion device and a domain-wall device. Our results will be the basis of a
hybrid device made of skyrmions and domain walls, where the encoded information
in domain walls is converted into skyrmions, and then read out by converting the
skyrmions back to domain walls after a functional control of the skyrmions. Such
a device has the potential to outperform domain-wall racetrack memory because of
the combined advantages of domain walls and skyrmions for spintronics
application.
PMID- 25115979
TI - Chronic fibrosing osteomyelitis: a position statement.
AB - Chronic Fibrosing Osteomyletis (CFO) is a commonly found condition which is often
undiagnosed because of its co-morbidities with other systemic conditions.
Clinicians should consider CFO in their differential diagnosis when confronted
with complex head, neck and facial pain patients who present with multi
symptom/systems overlay. A multi-disciplinary approach is often required for
proper patient diagnosis and treatment.
PMID- 25115978
TI - The Swiss Systemic lupus erythematosus Cohort Study (SSCS) - cross-sectional
analysis of clinical characteristics and treatments across different medical
disciplines in Switzerland.
AB - OBJECTIVES: To describe disease characteristics and treatment modalities in a
multidisciplinary cohort of systemic lupus erythematosus (SLE) patients in
Switzerland. METHODS: Cross-sectional analysis of 255 patients included in the
Swiss SLE Cohort and coming from centres specialised in Clinical Immunology,
Internal Medicine, Nephrology and Rheumatology. Clinical data were collected with
a standardised form. Disease activity was assessed using the Safety of Estrogens
in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA
SLEDAI), an integer physician's global assessment score (PGA) ranging from 0
(inactive) to 3 (very active disease) and the erythrocyte sedimentation rate
(ESR). The relationship between SLE treatment and activity was assessed by
propensity score methods using a mixed-effect logistic regression with a random
effect on the contributing centre. RESULTS: Of the 255 patients, 82% were women
and 82% were of European ancestry. The mean age at enrolment was 44.8 years and
the median SLE duration was 5.2 years. Patients from Rheumatology had a
significantly later disease onset. Renal disease was reported in 44% of patients.
PGA showed active disease in 49% of patients, median SLEDAI was 4 and median ESR
was 14 millimetre/first hour. Prescription rates of anti-malarial drugs ranged
from 3% by nephrologists to 76% by rheumatologists. Patients regularly using anti
malarial drugs had significantly lower SELENA-SLEDAI scores and ESR values.
CONCLUSION: In our cohort, patients in Rheumatology had a significantly later SLE
onset than those in Nephrology. Anti-malarial drugs were mostly prescribed by
rheumatologists and internists and less frequently by nephrologists, and appeared
to be associated with less active SLE.
PMID- 25115980
TI - Differentiation in the microbial ecology and activity of suspended and attached
bacteria in a nitritation-anammox process.
AB - A directed differentiation between the biofilm and suspension was observed in the
molecular microbial ecology and gene expression of different bacteria in a
biofilm nitritation-anammox process operated at varying hydraulic residence times
(HRT) and nitrogen loading rates (NLR). The highest degree of enrichment observed
in the biofilm was of anaerobic ammonia-oxidizing bacteria (AMX) followed by that
of Nitrospira spp. related nitrite-oxidizing bacteria (NOB). For AMX, a major
shift from Candidatus "Brocadia fulgida" to Candidatus "Kuenenia stuttgartiensis"
in both suspension and biofilm was observed with progressively shorter HRT, using
discriminatory biomarkers targeting the hydrazine synthase (hzsA) gene. In
parallel, expression of the hydrazine oxidoreductase gene (hzo), a functional
biomarker for AMX energy metabolism, became progressively prominent in the
biofilm. A marginal but statistically significant enrichment in the biofilm was
observed for Nitrosomonas europaea related ammonia-oxidizing bacteria (AOB). In
direct contrast to AMX, the gene expression of ammonia monooxygenase subunit A
(amoA), a functional biomarker for AOB energy metabolism, progressively increased
in suspension. Using gene expression and biomass concentration measures in
conjunction, it was determined that signatures of AOB metabolism were primarily
present in the biofilm throughout the study. On the other hand, AMX metabolism
gradually shifted from being uniformly distributed in both the biofilm and
suspension to primarily the biofilm at shorter HRTs and higher NLRs. These
results therefore highlight the complexity and key differences in the microbial
ecology, gene expression and activity between the biofilm and suspension of a
nitritation-anammox process and the biokinetic and metabolic drivers for such
niche segregation.
PMID- 25115981
TI - [Uncommon clinical manifestations of cutaneous leishmaniasis].
AB - Cutaneous leishmaniasis is one of the most common dermatoses of the tropics. A
major focus of this disease is the Syrian city of Aleppo, after which it was
named in many textbooks ("Aleppo boil"). The first cases of cutaneous
leishmaniasis were reported from Aleppo particularly more than 100 years ago.
Syria is one of the most affected countries worldwide. This disease used to be
well documented until the onset of the war in Syria in 2012, which is also
supported by the numbers of the World Health Organisation (WHO), and Aleppo used
to be the most affected Syrian city. Since 2012, the documentation of cutaneous
leishmaniasis in Syria is no longer possible. An outbreak of cutaneous
leishmaniasis has been detected especially in the besieged regions due to missing
prevention measures against the sandflies and a lack of medical care. A short
summary of the epidemiologic situation in Syria as well as outstanding and
uncommon clinical manifestations of cutaneous leishmaniasis in Aleppo are
presented.
PMID- 25115982
TI - [Comedo or basal cell carcinoma?].
PMID- 25115987
TI - 57Fe Mossbauer studies across the spin density wave transition in BaFe2-xRuxAs2.
AB - Mossbauer measurements have been carried out in powdered single crystalline
samples of BaFe(2-x)RuxAs(2), for Ru concentration in the x = 0.0-0.5 range. The
internal hyperfine field (B(hf)) measured at 5 K is found to decrease with an
increase in Ru concentration, consistent with the disappearance of a magnetic
ground state with Ru substitution. The temperature dependent Mossbauer
measurements have been used to study the evolution of magnetic ordering at the Fe
sites, in samples with a Ru fraction of x = 0.1 and 0.5. From the analysis of the
data, it is surmised that the isomer shift increases with a decrease in
temperature, with a characteristic slope change at the structural transition in
both samples studied. In both the x = 0.1 and x = 0.5 samples, a low B(hf)
centred around 0.5 Tesla is seen to occur well above the structural transition
temperature, the contribution from which is suppressed with a decrease in
temperature. Below the structural transition temperature, a bimodal distribution
of B(hf) centred at about 3 Tesla and 5 Tesla emerges, the contribution from
which increases with a further decrease in temperature. Spin polarized density
functional calculations suggest the occurrence of different magnetic moments at
the Fe sites in the Ru substituted compounds, and provide a rationale for the
experimentally observed multimodel B(hf).
PMID- 25115983
TI - [Childhood granulomatous periorificial dermatitis].
AB - CASE REPORT: A 14-year-old patient of African ancestry presented with multiple
papules in the perioral, perinasal and periocular areas. Histopathology showed
sarcoidal granulomas. DIAGNOSIS: After exclusion of systemic sarcoidosis, the
diagnosis of childhood granulomatous periorificial dermatitis was made. THERAPY:
Topical treatment with erythromycin resulted in complete regression. CONCLUSION:
Childhood granulomatous periorificial dermatitis is mainly observed in dark
skinned children of African, Caribbean, or Asian origin. The nosological position
of the dermatosis is controversial. Originally classified as sarcoidosis,
childhood granulomatous periorificial dermatitis is now generally regarded as a
special form of perioral dermatitis.
PMID- 25115988
TI - 'Jumping around': exploring young women's behaviour and knowledge in relation to
sexual health in a remote Aboriginal Australian community.
AB - Sexual health indicators for young remote-living Aboriginal women are the worst
of all of Australian women. This study aimed to describe and explore young
women's behaviour and knowledge in relation to sexual health, as well as to
provide health professionals with cross-cultural insights to assist with health
practice. A descriptive ethnographic study was conducted, which included:
extended ethnographic field work in one remote community over a six-year period;
community observation and participation; field notes; semi-structured interviews;
group reproductive ethno-physiology drawing and language sessions; focus-group
sessions; training and employment of Aboriginal research assistants; and
consultation and advice from a local reference group and a Cultural Mentor.
Findings reveal that young women in this remote community have a very poor
biomedical understanding of sexually transmitted infections and contraception.
This is further compounded by not speaking English as a first language, low
literacy levels and different beliefs in relation to body functions. In their
sexual relationships, young women often report experiences involving multiple
casual partners, marijuana use and violence. Together, the findings contribute to
a better understanding of the factors underlying sexual health inequity among
young Aboriginal women in Australia.
PMID- 25115989
TI - Treatment of bone metastases in urologic malignancies.
AB - The skeletal system is the most common site of metastatic cancer spread. Bone
metastases are often associated with severe morbidity, pain and functional
impairment. Timely diagnosis and proper treatment may decrease morbidity, improve
quality of life and in some cases even improve survival. External beam
radiotherapy may effectively give pain relief in patients with painful bone
metastases. In bone metastases from castration-resistant prostate cancer or
urothelial bladder cancer, treatment with zoledronic acid or denosumab may reduce
skeletal-related events. In contrast to castration-resistant prostate cancer, in
patients with bone metastases from bladder cancer such treatment may even improve
survival. On the other hand, the efficacy of these agents is questionable in
patients with bone involvement from metastatic renal cell carcinoma or germ cell
tumors. When bisphosphonates or denosumab are considered in such cases, the
potential benefits of treatment should be critically weighed against the risk of
side effects. In germ cell tumors, bone metastases may be cured by cisplatin
based chemotherapy, however, there are only limited data on the specific
management of residual disease. Oligometastases may be treated by stereotactic
radiotherapy or--especially in patients with renal cell carcinoma--by surgical
resection and endoprosthetic replacement. Limited data are available on the
management of bone involvement in germ cell tumors. Decisions on the resection or
local radiotherapy of residual disease should be individualized considering the
overall response and the feasibility and risks of resection.
PMID- 25115991
TI - Temperature response of denitrification and anaerobic ammonium oxidation rates
and microbial community structure in Arctic fjord sediments.
AB - The temperature dependency of denitrification and anaerobic ammonium oxidation
(anammox) rates from Arctic fjord sediments was investigated in a temperature
gradient block incubator for temperatures ranging from -1 to 40 degrees C.
Community structure in intact sediments and slurry incubations was determined
using Illumina SSU rRNA gene sequencing. The optimal temperature (Topt ) for
denitrification was 25-27 degrees C, whereas anammox rates were optimal at 12-17
degrees C. Both denitrification and anammox exhibited temperature responses
consistent with a psychrophilic community, but anammox bacteria may be more
specialized for psychrophilic activity. Long-term (1-2 months) warming
experiments indicated that temperature increases of 5-10 degrees C above in situ
had little effect on the microbial community structure or the temperature
response of denitrification and anammox. Increases of 25 degrees C shifted
denitrification temperature responses to mesophilic with concurrent community
shifts, and anammox activity was eliminated above 25 degrees C. Additions of low
molecular weight organic substrates (acetate and lactate) caused increases in
denitrification rates, corroborating the hypothesis that the supply of organic
substrates is a more dominant control of respiration rates than low temperature.
These results suggest that climate-related changes in sinking particulate flux
will likely alter rates of N removal more rapidly than warming.
PMID- 25115992
TI - Bivalirudin versus unfractionated heparin for residual thrombus burden: a
frequency-domain optical coherence tomography study.
AB - OBJECTIVES: This study aimed to compare the effect of bivalirudin and
unfractionated heparin (UFH) on residual thrombus burden assessed by frequency
domain optical coherence tomography (FD-OCT), and on angiographic indices of
microvascular obstruction (MVO). BACKGROUND: The efficacy of bivalirudin to
inhibit thrombus formation inside the stent during percutaneous coronary
interventions (PCI) as compared to UFH is unknown. METHODS: Sixty patients with
coronary artery disease who underwent post-PCI FD-OCT were studied, including 20
patients treated with bivalirudin and 40 control patients treated with UFH,
matched by clinical presentation, stent characteristics, and periprocedural
medications. In-stent thrombus volume, thrombus score (number of quadrants with
thrombus), and thrombus type (white/red) were assessed by FD-OCT. Thrombolysis in
myocardial infarction (TIMI) flow grade, corrected TIMI frame count (cTFC), and
Quantitative Blush Evaluator (QuBE) score were recorded. RESULTS: Patients
treated with bivalirudin showed similar thrombus volume (0.14 mm(3) [0.00-0.88]
vs. 0.13 mm(3) [0.00-0.63], P = 0.962), thrombus score (10 [0-25] vs. 8 [0-21], P
= 0.849) and thrombus length (1.70 mm [0.00-4.10] vs. 1.40 mm [0.00-4.05], P =
0.968], as compared with patients treated with UFH. Patients in the bivalirudin
group showed lower proportion of white thrombus (55.5% vs. 78.6%, P = 0.016).
There was no significant difference in TIMI flow grade, cTFC, and QuBE score
between the two groups. CONCLUSIONS: The present study showed similar residual
thrombus burden and angiographic indices of MVO immediately after PCI between
patients treated with bivalirudin and those treated with UFH.
PMID- 25115993
TI - Sterile-filtered saliva is a strong inducer of IL-6 and IL-8 in oral fibroblasts.
AB - OBJECTIVES: Saliva has been implicated to support oral wound healing, a process
that requires a transient inflammatory reaction. However, definitive proof that
saliva can provoke an inflammatory response remained elusive. MATERIALS AND
METHODS: We investigated the ability of freshly harvested and sterile-filtered
saliva to cause an inflammatory response of oral fibroblasts and epithelial
cells. The expression of cytokines and chemokines was assessed by microarray, RT
PCR, immunoassays, and Luminex technology. The involvement of signaling pathways
was determined by Western blot analysis and pharmacologic inhibitors. RESULTS: We
report that sterile-filtered whole saliva was a potent inducer of IL-6 and IL-8
in fibroblasts from the gingiva, the palate, and the periodontal ligament, but
not of oral epithelial cells. This strong inflammatory response requires nuclear
factor-kappa B and mitogen-activated protein kinase signaling. The pro
inflammatory capacity is heat stable and has a molecular weight of <40 kDa.
Genome-wide microarrays and Luminex technology further revealed that saliva
substantially increased expression of other inflammatory genes and various
chemokines. To preclude that the observed pro-inflammatory activity is the result
of oral bacteria, sterile-filtered parotid saliva, collected under almost aseptic
conditions, was used and also increased IL-6 and IL-8 expression in gingiva
fibroblasts. The inflammatory response was, furthermore, independent of MYD88, an
adapter protein of the Toll-like receptor signaling pathway. CONCLUSIONS: We
conclude that saliva can provoke a robust inflammatory response in oral
fibroblasts involving the classical nuclear factor-kappa B and mitogen-activated
protein kinase signaling pathway. CLINICAL RELEVANCE: Since fibroblasts but not
epithelial cells show a strong inflammatory response, saliva may support the
innate immunity of defect sites exposing the oral connective tissue.
PMID- 25115994
TI - Evaluation of a new oral health scale of infectious potential based on the
salivary microbiota.
AB - OBJECTIVES: The objective of this study is to analyse the correlation of our own
design of oral health scale (grades 0 and 1-better oral health vs. grades 2 and 3
poorer oral health) with the salivary microbiota. PATIENTS AND METHODS: The oral
health scale we elaborated was evaluated in 100 adults (25 patients from each
global oral health grade). Saliva samples collected from these patients were
analysed using microbiological culture techniques, determining the
presence/absence and the concentrations of some odontopathogens and
periodontopathogens. RESULTS: In comparison with the global oral health grades 0
1, the grades 2-3 presented significantly higher values for the presence of
odontopathogens (78 vs. 38 %; Streptococcus mutans, Lactobacillus spp. and
Actinomyces spp.) and periodontopathogens (100 vs. 90 %; Aggregatibacter
actinomycetemcomitans, Campylobacter spp., Fusobacterium spp. and Prevotella
gingivalis). In comparison with the grades 0-1, the grades 2-3 presented
significantly higher values for the concentrations (CFU/mL log10) of facultative
anaerobes, strict anaerobes, odontopathogens (S. mutans, Lactobacillus spp. and
Actinomyces spp.) and periodontopathogens (A. actinomycetemcomitans,
Capnocytophaga spp., Campylobacter spp. and Fusobacterium spp.). CONCLUSION: Our
new global oral health scale shows a positive correlation with the detection and
quantification of certain odontopathogens and periodontopathogens present in the
saliva, confirming their possible infectious potential. CLINICAL RELEVANCE: Our
own design of oral health scale could be particularly useful for the
epidemiological study of different populations, the evaluation of the influence
of oral health on the development of certain systemic diseases as well as the
analysis of inter- and intra-individual variability of the oral microbiota in
relation to the different grades of the oral health scale.
PMID- 25115997
TI - Continuous and scalable fabrication of bioinspired dry adhesives via a roll-to
roll process with modulated ultraviolet-curable resin.
AB - A simple yet scalable strategy for fabricating dry adhesives with mushroom-shaped
micropillars is achieved by a combination of the roll-to-roll process and
modulated UV-curable elastic poly(urethane acrylate) (e-PUA) resin. The e-PUA
combines the major benefits of commercial PUA and poly(dimethylsiloxane) (PDMS).
It not only can be cured within a few seconds like commercial PUA but also
possesses good mechanical properties comparable to those of PDMS. A roll-type
fabrication system equipped with a rollable mold and a UV exposure unit is also
developed for the continuous process. By integrating the roll-to-roll process
with the e-PUA, dry adhesives with spatulate tips in the form of a thin flexible
film can be generated in a highly continuous and scalable manner. The fabricated
dry adhesives with mushroom-shaped microstructures exhibit a strong pull-off
strength of up to ~38.7 N cm(-2) on the glass surface as well as high durability
without any noticeable degradation. Furthermore, an automated substrate
transportation system equipped with the dry adhesives can transport a 300 mm Si
wafer over 10,000 repeating cycles with high accuracy.
PMID- 25115995
TI - Effects of sodium hypoclorite as disinfectant material previous to pulpotomies in
primary teeth.
AB - OBJECTIVES: Sodium hypochlorite (NaOCl) can be used to promote healing vital
pulpotomies as an antibacterial agent. The aim of the present study was to
histologically analyze the pulpal response of human primary teeth pulp following
calcium hydroxide (CH) and mineral trioxide aggregate (MTA) pulpotomies with and
without 5% NaOCl. MATERIALS AND METHODS: One hundred twenty-eight primary molars
were randomly divided into two main groups according to pulpotomy material
(CH/MTA) and into two subgroups according to selected cleansing agent
(NaOCl/physiologic saline) used in the pulpotomy procedure. Thirty-four
successfully treated teeth whose successor roots had completed formation of at
least two thirds of their lengths were extracted for histological evaluation.
Fisher's exact test, Pearson's Chi-square test, and Mann-Whitney U test with
Bonferroni correction were used for statistical analysis. RESULTS: No significant
differences in any of the tested parameters were observed between the NaOCl and
physiologic saline subgroups of either the CH or MTA groups. Pulpal inflammation
was significantly higher in the CH-treated teeth as compared with the MTA-treated
teeth, whereas hard tissue bridge formation was significantly higher in the MTA
treated teeth as compared with the CH-treated teeth but regardless of cleansing
agent (p < 0.025). CONCLUSIONS: The use of NaOCl does not affect the success of
CH or MTA pulpotomies. Regardless of cleansing agent, MTA was found to be
superior to CH. CLINICAL RELEVANCE: The proper medicament selection is more
important than the choice of cleaning agent in vital pulpotomies.
PMID- 25115998
TI - Estimation of the use of antibiotics in the small ruminant industry in The
Netherlands in 2011 and 2012.
AB - The aim of this study was to estimate the quantity of antibiotics and classes of
antibiotics used in the small ruminant industry in the Netherlands in 2011 and
2012. Twelve large veterinary practices, located throughout the Netherlands were
selected for this study. All small ruminant farms associated with these practices
that had complete records on the quantity of antibiotics prescribed were
included. The veterinary practices provided data on all antibiotics prescribed,
and the estimated animal used daily dose of antibiotics per year (AUDD/Y) was
calculated for each farm. The median AUDD/Y in small ruminant farms was zero in
both years (mean 0.60 in 2011, and 0.62 in 2012). The largest quantity of
antibiotic use was observed in the professional goat industry (herds of >=32
goats) with a median AUDD/Y of 1.22 in 2011 and 0.73 in 2012. In the professional
sheep industry (flocks of >=32 sheep), the median AUDD/Y was 0 in 2011 and 0.10
in 2012. In the small scale industry (flocks or herds of <32 sheep or goats), the
median AUDD/Y never exceeded 0. The most frequently prescribed antibiotics in the
small scale industry and professional sheep farms belonged to the penicillin
class. In professional goat farms, antibiotics of the aminoglycoside class were
most frequently prescribed. This study provides the first assessment on the
quantity of antibiotic use in the small ruminant industry. Given a comparable
attitude towards antibiotic use, these results might be valid for small ruminant
populations in other north-western European countries as well. The antibiotic use
in the small ruminant industry appeared to be low, and is expected to play a
minor role in the development of antibiotic resistance. Nevertheless, several
major zoonotic bacterial pathogens are associated with the small ruminant
industry, and it remains important that antibiotics are used in a prudent way.
PMID- 25116000
TI - Development of an in vitro screen for compound bioaccumulation in Haemonchus
contortus.
AB - The objective of the current study was to establish an in vitro screen and a
highly sensitive analytical assay to delineate key physicochemical properties
that favor compound bioaccumulation in the L3 life stage of a Haemonchus
contortus isolate. Time-dependent studies revealed that absorption and
elimination kinetics during the first 6 hr of exposure were sufficient to achieve
maximum bioaccumulation for the majority of compounds tested. In subsequent
studies, the larvae were incubated for 6 hr in a medium containing 146 compounds
(5 MUM initial concentration), including both human and veterinary medicines,
characterized by a broad range of physicochemical properties. Bioaccumulation of
the compounds by the nematodes was determined, and multiple physicochemical
descriptors were selected for correlation. Data analysis using Bayes
classification model and partial least-square regression revealed that clogD7.4,
rotatable bond, E-state, and hydrogen bond donor each correlated with compound
bioaccumulation in H. contortus L3. The finding that lipophilicity was critical
for transcuticle compound permeation was consistent with previous studies in
other parasitic species and in adult H. contortus . The finding of additional
physicochemical properties that contribute to compound conformational
flexibility, polarity, and electrotopological state shed light on the mechanisms
governing transcuticle permeation. The relatively poor correlation between
transcuticle and transmembrane permeation indicated the distinct mechanisms of
compound permeation, likely due to the different constituents, and their
contributions to overall transport function, of the lipid membranes and the
porous collagen barrier of the nematode cuticle. Our study, for the first time,
establishes a high-throughput screen for compound bioaccumulation in a parasitic
nematode and further elucidates physicochemical factors governing transcuticular
permeation of compounds. Application of this methodology will help explain the
basis for discrepancies observed in receptor binding and whole organism potency
assays and facilitate incorporation of drug delivery principles in the design of
candidate anthelmintics.
PMID- 25115999
TI - Cognitive impairment in myotonic dystrophy type 1 is associated with white matter
damage.
AB - OBJECTIVE: To investigate grey (GM) and white matter (WM) abnormalities and their
effects on cognitive and behavioral deficits in a large, phenotypically and
genotypically well-characterized cohort of classic adult (aDM1, age at onset >=
20 years) or juvenile (jDM1, age at onset <20 years) patients with myotonic
dystrophy type 1 (DM1). METHODS: A case-control study including 51 DM1 patients
(17 jDM1 and 34 aDM1) and 34 controls was conducted at an academic medical
center. Clinical, cognitive and structural MRI evaluations were obtained.
Quantitative assessments of regional GM volumes, WM hyperintensities (WMHs), and
microstructural WM tract damage were performed. The association between
structural brain damage and clinical and cognitive findings was assessed.
RESULTS: DM1 patients showed a high prevalence of WMHs, severe regional GM
atrophy including the key nodes of the sensorimotor and main cognitive brain
networks, and WM microstructural damage of the interhemispheric, corticospinal,
limbic and associative pathways. WM tract damage extends well beyond the focal
WMHs. While aDM1 patients had severe patterns of GM atrophy and WM tract damage,
in jDM1 patients WM abnormalities exceeded GM involvement. In DM1, WMHs and
microstructural damage, but not GM atrophy, correlated with cognitive deficits.
CONCLUSIONS: WM damage, through a disconnection between GM structures, is likely
to be the major contributor to cognitive impairment in DM1. Our MRI findings in
aDM1 and jDM1 patients support the hypothesis of a degenerative (premature aging)
origin of the GM abnormalities and of developmental changes as the principal
substrates of microstructural WM alterations in DM1.
PMID- 25116001
TI - Treatment of alpha(0)-thalassemia (--(SEA)/--(SEA)) via serial fetal and post
natal transfusions: Can early fetal intervention improve outcomes?
AB - OBJECTIVE AND IMPORTANCE: Homozygous Southeast Asian alpha-thalassemia mutation (
-(SEA)/--(SEA)) results in deletion of all alpha-globin genes (alpha(0)
thalassemia). Since all alpha-globin chains are absent, hemoglobin F cannot be
synthesized, and hemoglobin Bart's becomes the dominant fetal hemoglobin.
Hemoglobin Bart's is a gamma tetramer with a very high oxygen affinity, thus
oxygen delivery to the tissues is poor. Clinical manifestations include severe
fetal anemia, hydrops fetalis, fetal demise, and high risk of neurodevelopmental
impairment in the rare survivors. CLINICAL PRESENTATION: A 39-year-old Vietnamese
woman presented to our center at 28 0/7 weeks' gestation with fetal alpha(0)
thalassemia (--(SEA)/--(SEA) type deletion) and ultrasound markers suggestive of
severe fetal anemia. INTERVENTION: The fetus was treated with four intrauterine
transfusions followed by post-natal chronic transfusions. Formal
neurodevelopmental testing (Battelle Developmental Inventory, Second Edition) was
performed at 18 months of age, and the developmental quotient was 93 (32nd
percentile) with all subdomains noted within normal limits, indicating overall
intact neurodevelopment. CONCLUSION: We posit that earlier diagnosis and fetal
treatment, prior to clinical findings suggestive of fetal anemia, may improve
long-term outcomes by enhancing oxygen delivery to the tissues of the developing
fetus.
PMID- 25116002
TI - Decreased inter-hemispheric connectivity in anterior sub-network of default mode
network and cerebellum: significant findings in major depressive disorder.
AB - The issue of inter-hemispheric connectivity is an emerging new area in
understanding the pathophysiology of depression. This study was designed to
analyse the pattern of inter-hemispheric connectivity in patients with major
depressive disorder (MDD). The resting-state functional magnetic resonance
imaging (RFMRI) was acquired in all enrolled patients and controls. We used a
method of voxel-mirrored homotopic connectivity (VMHC) to estimate the
significant differences in inter-hemispheric connectivity between 44 patients
with first-episode medication-naive MDD and 27 normal controls. The patients and
controls were matched for age and gender. The patients with first-episode
medication-naive MDD showed lower VMHC than normal controls in bilateral medial
frontal cortex, anterior cingulate and cerebellar posterior lobe. The strength of
inter-hemispheric connectivity VMHC value was negatively correlated with clinical
severity of MDD. From the results, we suggested that decreased inter-hemispheric
connectivity in the anterior sub-network of the default mode network and the
cerebellar posterior lobe might represent an emerging finding in the
pathophysiology for MDD.
PMID- 25116003
TI - Multicolour nonlinearly bound chirped dissipative solitons.
AB - The dissipative soliton regime is one of the most advanced ways to generate high
energy femtosecond pulses in mode-locked lasers. On the other hand, the
stimulated Raman scattering in a fibre laser may convert the excess energy out of
the coherent dissipative soliton to a noisy Raman pulse, thus limiting its
energy. Here we demonstrate that intracavity feedback provided by re-injection of
a Raman pulse into the laser cavity leads to formation of a coherent Raman
dissipative soliton. Together, a dissipative soliton and a Raman dissipative
soliton (of the first and second orders) form a two (three)-colour stable complex
with higher total energy and broader spectrum than those of the dissipative
soliton alone. Numerous applications can benefit from this approach, including
frequency comb spectroscopy, transmission lines, seeding femtosecond parametric
amplifiers, enhancement cavities and multiphoton fluorescence microscopy.
PMID- 25116005
TI - Back to the future: examining type 2 diabetic vasculature using the gestational
diabetic placenta.
AB - Understanding the association between the intrauterine hyperglycemic milieu and
the development of adult diabetic vasculopathy is of particular relevance in
India, where diabetes and vascular disease are prevalent. The gestational
diabetes mellitus placenta is a valuable tool to examine blood vessels that have
been exposed to hyperglycemic cues. We report an interesting observation in a
cohort of gestational diabetes mellitus foetal placental vasculature from South
India. Transmission electron microscopy demonstrated pericyte detachment and
pericyte ghost cells reminiscent of adult type 2 diabetic retinopathy, in
gestational diabetes mellitus foetal placental blood vessels that were not
observed in non-gestational diabetes mellitus placentas (p <=0.001). Endothelial
cell irregularity was observed in 76% gestational diabetes mellitus foetal blood
vessels as compared with 10.4% non-gestational diabetes mellitus placental
vasculature (p <=0.001). Other abnormalities noted in gestational diabetes
mellitus placenta included mitochondrial abnormalities, increased micro vessel
density and thickening of basement membranes. These results suggest that adult
type 2 diabetic vasculopathy has developmental origins in utero.
PMID- 25116006
TI - Multiple approaches to predicting oxygen and glucose consumptions by HepG2 cells
on porous scaffolds in an axial-flow bioreactor.
AB - In this study, the distribution of oxygen and glucose was evaluated along with
consumption by hepatocytes using three different approaches. The methods include
(i) Computational Fluid Dynamics (CFD) simulation, (ii) residence time
distribution (RTD) analysis using a step-input coupled with segregation model or
dispersion model, and (iii) experimentally determined consumption by HepG2 cells
in an open-loop. Chitosan-gelatin (CG) scaffolds prepared by freeze-drying and
polycaprolactone (PCL) scaffolds prepared by salt leaching technique were
utilized for RTD analyses. The scaffold characteristics were used in CFD
simulations i.e. Brinkman's equation for flow through porous medium, structural
mechanics for fluid induced scaffold deformation, and advection-diffusion
equation coupled with Michaelis-Menten rate equations for nutrient consumption.
With the assumption that each hepatocyte behaves like a micro-batch reactor
within the scaffold, segregation model was combined with RTD to determine exit
concentration. A flow rate of 1 mL/min was used in the bioreactor seeded with 0.6
* 10(6) HepG2 cells/cm(3) on CG scaffolds and oxygen consumption was measured
using two flow-through electrodes located at the inlet and outlet. Glucose in the
spent growth medium was also analyzed. RTD results showed distribution of
nutrients to depend on the surface characteristics of scaffolds. Comparisons of
outlet oxygen concentrations between the simulation results, and experimental
results showed good agreement with the dispersion model. Outlet oxygen
concentrations from segregation model predictions were lower. Doubling the cell
density showed a need for increasing the flow rate in CFD simulations. This
integrated approach provide a useful strategy in designing bioreactors and
monitoring tissue regeneration.
PMID- 25116004
TI - The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the
renal system.
AB - Diabetic nephropathy (DN) affects an estimated 20%-40% of patients with type 2
diabetes mellitus (T2DM). Key modifiable risk factors for DN are albuminuria,
anaemia, dyslipidaemia, hyperglycaemia and hypertension, together with lifestyle
factors, such as smoking and obesity. Early detection and treatment of these risk
factors can prevent DN or slow its progression, and may even induce remission in
some patients. DN is generally preceded by albuminuria, which frequently remains
elevated despite treatment in patients with T2DM. Optimal treatment and
prevention of DN may require an early, intensive, multifactorial approach,
tailored to simultaneously target all modifiable risk factors. Regular monitoring
of renal function, including urinary albumin excretion, creatinine clearance and
glomerular filtration rate, is critical for following any disease progression and
making treatment adjustments. Dipeptidyl peptidase (DPP)-4 inhibitors and sodium
glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels without
additional risk of hypoglycaemia, and may also reduce albuminuria. Further
investigation of the potential renal benefits of DPP-4 and SGLT2 inhibitors is
underway.
PMID- 25116008
TI - [Biochemical markers after trauma].
PMID- 25116007
TI - Activation of nuclear factor kappa B in the hepatic stellate cells of mice with
schistosomiasis japonica.
AB - Schistosomiasis japonica is a serious tropical parasitic disease in humans, which
causes inflammation and fibrosis of the liver. Hepatic stellate cells (HSCs) are
known to play an important role in schistosome-induced fibrosis, but their role
in schistosome-induced inflammation is still largely unknown. Here, we use a
murine model of schistosomiasis japonica to investigate the role that nuclear
factor kappa B (NF-kappaB), a critical mediator of inflammatory responses, plays
in schistosome-induced inflammation. We revealed that NF-kappaB was significantly
activated in HSCs at the early stage of infection, but not at later stages. We
also show that the expression levels of several chemokines regulated by NF-kappaB
signaling (Ccl2, Ccl3 and Ccl5) were similarly elevated at early infection. TLR4
signaling, one of the strongest known inducers of NF-kappaB activation, seemed
not activated in HSCs post-infection. Importantly, we found that levels of miR
146 (a known negative regulator of NF-kappaB signaling) in HSCs opposed those of
NF-kappaB signaling, elevating at later stage of infection. These results
indicate that HSCs might play an important role in the progression of hepatic
schistosomiasis japonica by linking liver inflammation to fibrosis via NF-kappaB
signaling. Moreover, our work suggests that miR-146 appeared to regulate this
process. These findings are significant and imply that manipulating the function
of HSCs by targeting either NF-kappaB signaling or miR-146 expression may provide
a novel method of treating hepatic schistosomiasis japonica.
PMID- 25116009
TI - [Biomarkers in pediatric polytrauma].
AB - BACKGROUND: Trauma represents one of the leading causes of death in children.
Beside an injury pattern that differs from adult trauma patients, children seem
to develop multiple organ dysfunction syndrome (MODS) less frequently. Compared
to adult MODS, pediatric MODS has also been described to occur earlier in the
posttraumatic course. METHOD: Biomarkers for early identification of patients at
high-risk for posttraumatic complications are of high clinical relevance.
However, little is known from clinical studies about the relevance of biomarkers
during the posttraumatic course. AIM: Therefore, the purpose of this review is to
summarize current knowledge on this topic in order to investigate the prognostic
significance of different parameters.
PMID- 25116010
TI - [Microarrays as biomarkers in trauma].
AB - BACKGROUND: The traditional hypothesis-driven scientific approach cannot so far
sufficiently elucidate complex pathophysiologies, such as posttraumatic systemic
inflammation and subsequent multiple organ failure. This complex system includes
different biological and functional levels, the genome, the transcriptome, the
proteome, the biome (cells), the organs and finally the whole organism. METHODS:
Microarray techniques enable a simultaneous search for these different biological
levels and their functional relationships on a large scale and to discover new
functional pathways and networks and potentially new biomarkers for different
pathologies. Microarray technologies lead to a new paradigm in science, the
hypothesis-generating approach. AIM: This article reviews important microarray
findings in trauma and systemic inflammation research and discusses potentials
and limitations of these biotechnological screening methods.
PMID- 25116011
TI - [Diagnostic biomarkers in traumatic brain injury].
AB - BACKGROUND: Despite advances in medicine in head trauma management, traumatic
brain injury (TBI) still remains a serious health concern, affecting people
regardless of age. It is a leading cause of morbidity and mortality particularly
in children and young adults. Therefore, studies are being carried out to try to
establish reliable biomarkers to improve the accuracy of TBI diagnosis and
associated secondary pathologies. METHODS: Implementation of valid TBI biomarkers
could possibly reduce the necessity to use computed cranial tomography (CCT),
especially in patients suffering from mild TBI to rule out intracranial bleeding.
AIM: This review provides a critical assessment of biomarkers currently under
investigation and their clinical value for the diagnosis, treatment and outcome
prediction of TBI.
PMID- 25116012
TI - [Cytokines as biomarkers in polytraumatized patients].
AB - BACKGROUND: Multiple trauma can lead to posttraumatic complications such as
systemic inflammatory response syndrome (SIRS), multiple organ dysfunction
syndrome (MODS), and sepsis. Currently, these complications are monitored using
clinical and organ-specific parameters. The immune system is activated by trauma.
Cytokines, which are the messenger molecules of this system, can be determined in
serum. Furthermore, they are associated with the intensity of the inflammatory
and anti-inflammatory reactions. AIM: This review describes clinical studies that
measured cytokines such as TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10 to
prognosticate posttraumatic complications. On the other hand, IL-6 can be helpful
in deciding which primary operation to perform, i.e., external fixator or
intramedullary nail. Moreover, IL-6 indicates the strength of the immune
reaction. Thereby, it may help in determining the optimal time for secondary
surgery.
PMID- 25116014
TI - [Retraction Note to: Biodegradable screw vs a press-fit bone plug fixation for
ACL reconstruction. A prospective randomized study].
PMID- 25116013
TI - [Scapholunate lesions].
AB - Injuries to the scapholunate ligament are the most frequent cause of carpal
instability. Therefore, if a scapholunate lesion is not diagnosed, it may result
in a severe dysfunction of the wrist. This review describes the anatomy, and the
kinematics of the wrist with an intact as well as a disrupted scapholunate
ligament. The diagnostic of an isolated ligament lesion and a ligament injury
associated with a fracture of the distal radius is presented. Finally, an
algorithm for treatment based on the stage of injury is proposed.
PMID- 25116016
TI - [Non-valvular atrial fibrillation: direct thrombin inhibitors versus VKA].
PMID- 25116017
TI - [Does transcatheter aortic-valve replacement reduce mortality?--TAVR: good
prognosis due to improved protheses].
PMID- 25116015
TI - Targeted high-throughput sequencing identifies pathogenic mutations in KCNQ4 in
two large Chinese families with autosomal dominant hearing loss.
AB - Autosomal dominant non-syndromic hearing loss (ADNSHL) is highly heterogeneous,
among them, KCNQ4 is one of the most frequent disease-causing genes. More than
twenty KCNQ4 mutations have been reported, but none of them were detected in
Chinese mainland families. In this study, we identified a novel KCNQ4 mutation in
a five generation Chinese family with 84 members and a known KCNQ4 mutation in a
six generation Chinese family with 66 members. Mutation screening of 30 genes for
ADNSHL was performed in the probands from thirty large Chinese families with
ADNSHL by targeted region capture and high-throughput sequencing. The candidate
variants and the co-segregation of the phenotype were verified by polymerase
chain reaction (PCR) amplification and Sanger sequencing in all ascertained
family members. Then we identified a novel KCNQ4 mutation p.W275R in exon 5 and a
known KCNQ4 mutation p.G285S in exon 6 in two large Chinese ADNSHL families
segregating with post-lingual high frequency-involved and progressive
sensorineural hearing loss. This is the first report of KCNQ4 mutation in Chinese
mainland families. KCNQ4, a member of voltage-gated potassium channel family, is
likely to be a common gene in Chinese patients with ADNSHL. The results also
support that the combination of targeted enrichment and high-throughput
sequencing is a valuable molecular diagnostic tool for autosomal dominant
hereditary deafness.
PMID- 25116018
TI - [Treatment of acute renal failure in Germany: a structural analysis].
AB - INTRODUCTION: There are no reliable data on the structure and practice of the
care of critically ill patients with acute renal failure in Germany. METHODS: We
carried out a detailed survey by sending a questionnaire to 2265 German Intensive
Care Units. The questionnaire contained 19 questions regarding renal replacement
therapy. RESULTS: 423 German intensive care units participated in the survey.
Most of the ICUs are headed interdisciplinary (47%) or by anesthesiologists
(30%), with significant differences depending on the size of the clinic, with
primarily interdisciplinary management in smaller clinics. The offered type of
renal replacement therapy varies significantly, the smaller the house the fewer
methods are available. Thus, intermittent dialysis procedures are offered only in
35% of hospitals with up to 400 beds. The indication for the initiation of acute
renal replacement therapy in intensive care is provided predominantly (53%) by an
anesthesiologist. A nephrologist is only involved in 22% of all intensive care
units. The indication is based primarily on a "clinical criteria", but these are
poorly defined. CONCLUSION: Our results demonstrate the need for cross
disciplinary standards for the treatment of acute renal failure in German
intensive care units.
PMID- 25116020
TI - [45-year-old woman with iron deficiency anemia].
PMID- 25116019
TI - [Endovascular therapy of an iatrogenic renal-artery-perforation after fenestrated
aortic-repair (fEVAR)].
AB - HISTORY AND ADMISSION FINDINGS: A 75-year-old patient was initially hospitalized
for therapy-evaluation of a an acquaint infrarenal abdominal-aortic-aneurysm,
with a maximum diameter of 5.3 cm. Medical history showed a known contained
rupture of the aneurysm. Except for a substituted Hypothyroidism and a COPD
Stadium II (GOLD), there were no other previous diseases known. EXAMINATIONS:
Laboratory showed a slight normochrome, normocytic anemia (hemoglobin 13 g/dl,
MCV and MCH were normal) together with a decreased total amount of erythrocytes
of 3.89/pl. TSH value was increased significantly at 7.960 mU/l. Initially
creatinine was measured at 1.02 mg/dl. Sonography and CT-scan of the abdominal
vessels had shown no new insights other than the aneurysm of the abdominal aorta.
A surgical revision was indicated. TREATMENT AND COURSE: After primarily
uncomplicated implantation of a fenestrated EVAR, the patient showed a
progressive hemoglobin loss concomitant with a considerable increase of renal
retention parameters. A "spurium"/false aneurysm of the right renal artery was
found, which moreover showed a retroperitoneal bleeding. The patient subsequently
underwent successful endovascular therapy in our clinic and was dismissed from
the hospital in good condition and without further complications. Follow up
controls showed no signs of new pathologies. CONCLUSION: "Direct" post-operative
complications after EVAR are a rarity. In our case, the interventional
endovascular approach of the bleeding from the right renal artery was a
successful and sufficient treatment of the potentially life-threatening
complication.
PMID- 25116023
TI - [Venous valve prosthesis--close to the biological model].
PMID- 25116022
TI - [New diagnostic tool for individual monitoring of urolithiasis risk and other
metabolic diseases].
AB - Urinary composition is the result of the interplay of all metabolic processes,
including all metabolites and toxins produced. Any change in urine composition
influences urinary supersaturation, the major thermodynamic driving force of
crystal formation. Urolithiasis is a wide-spread disease with a prevalence rate
of 4% to 10%. Formation risk of calcium-oxalate, by far the most common mineral
in uroliths, is quantified by the Bonn-Risk-Index (BRI). The BRI measures induced
crystal growth within native urine and shows superior diagnostic sensitivity and
specificity compared to other urolithiasis risk indices. The concept of BRI quick
test presented in this work allowes even untrained persons to easily determine
the urolithiasis risk. Many diseases lack a simple, easily accessible and cost
effective diagnostic approach to monitor their course and treatment success.
Since BRI takes into account every constituent of native urine, it can be used to
monitor a wide range of metabolic diseases.
PMID- 25116021
TI - [Non-cystic fibrosis bronchiectasis: diagnosis and treatment].
AB - Bronchiectasis is the term used for irreversibly dilated airways. Exact
epidemiological information on the frequency of bronchiectasis is not available,
but the morphological findings are increasingly detected and the associated
syndrome is more frequently diagnosed due to improved imaging techniques and
increased awareness among chest physicians. The workup of these patients includes
a wide panel of investigations guided by patient history and clinical
presentation. Despite thorough evaluation the aetiology frequently remains
unclear. Chronic infection with Pseudomonas aeruginosa is associated with a
severe course of the disease and its detection has impacts on the therapeutic
management. Chest physiotherapy, mucoactive substances and antibiotics are the
mainstay of therapy. In this review the evaluation of bronchiectasis and the
recent therapeutic insights for non-cystic fibrosis bronchiectasis are discussed.
PMID- 25116025
TI - ["Burnout"--is it a disease or rather a consequence of (work-) stress?].
AB - Burnout is a work related health impairment comprising three dimensions:
emotional exhaustion, depersonalisation and reduced personal accomplishment. Not
least because of the highly frequented term "burnout" within the German speaking
area, there is a rising interest in the connection of work related stress and
psychological and somatic complaints. Burnout is not a disease in the proper
sense but a physiological construct. Coherence between work related stress and
the development of psychological and somatic diseases has been proven by many
studies. However burnout requires a differential diagnostic categorisation.
Therapeutic procedures and prevention measures should be initiated based on the
forms and categorisation of work related stress.
PMID- 25116024
TI - [If the general practitioner has to decide: what is the evidence for the
selection of antidepressants?].
AB - The review summarises the evidence supporting the choice of an antidepressant in
primary care. We report current guidance on the choice of antidepressants and the
current use of antidepressants in Germany. Evidence for the comparative efficacy
of modern antidepressants, such as venlafaxine, duloxetine or agomelatine will be
summarized with respect to depressive and accompanying symptoms. Furthermore,
differences in adverse events between antidepressants will be reviewed.
PMID- 25116031
TI - Bandgap-engineered CdxZn1-xO nanowires as active regions for green-light-emitting
diodes.
AB - A green-light-emitting diode device was fabricated based on a p-type Sb-doped ZnO
segments/Cd-alloyed ZnO/n-type ZnO film/heteronanowires array structure. The
structures and chemical components of the heteronanowire sample were studied by
energy dispersive spectrometer, x-ray photoelectron spectrometer, etc, from which
the statuses of Cd and Sb in the sample were confirmed. Spatially resolved
photoluminescence measurement on a single heteronanowire revealed a large bandgap
shift in the Cd(x)Zn(1 - x)O active region. In electroluminescence
characterizations, the device showed that the green emission was centered at 550
nm, suggesting the successful formation and functioning of the double
heterojunction nanowire light-emitting diodes.
PMID- 25116026
TI - A proteomic glimpse into the initial global epigenetic changes during HIV
infection.
AB - HIV-1 replication requires the insertion of viral DNA into the host genome, which
is catalyzed by HIV-1 integrase. This integration event can lead to vast changes
in the chromatin landscape and gene transcription. In this study, we sought to
correlate the extensive changes of histone PTM abundances with the equally
dynamic shifts in host transcriptional activity. To fully capture the changes
that were occurring during the course of HIV-infection, we performed time-courses
in which we extracted both histones and mRNA from HIV-infected, UV-inactivated
HIV-infected and mock-infected SUP-T1 cells. We then analyzed the alterations to
histone PTM profiles using nano-LC-MS/MS, as well as the expression of chromatin
associated enzymes, such as histone deacetylases, acetyltransferases,
demethylases, methyltransferases, and histone chaperone proteins. As expected, we
observed major changes in histone PTM abundances, which we linked to massive
fluctuations in mRNA expression of associated chromatin enzymes. However, we find
few differences between HIV and HIVUV (UV-inactivated) infection, which suggests
that initial histone PTM changes during HIV infection are from the host in
response to the infection, and not due to the HIV virus manipulating the
transcriptional machinery. We believe that these preliminary experiments can
provide a basis for future forays into targeted manipulations of histone PTM
regulated aspects of HIV progression through its replication cycle.
PMID- 25116032
TI - In vitro three-dimensional bone tissue models: from cells to controlled and
dynamic environment.
AB - Most of our knowledge of bone cell physiology is derived from experiments carried
out in vitro on polystyrene substrates. However, these traditional monolayer cell
cultures do not reproduce the complex and dynamic three-dimensional (3D)
environment experienced by cells in vivo. Thus, there is a growing interest in
the use of 3D culture systems as tools for understanding bone biology. These in
vitro-engineered systems, less complex than in vivo models, should ultimately
recapitulate and control the main biophysical, biochemical, and biomechanical
cues that define the in vivo bone environment, while allowing their monitoring.
This review focuses on state-of-the-art and the current advances in the
development of 3D culture systems for bone biology research. It describes more
specifically advantages related to the use of such systems, and details main
characteristics and challenges associated with its three main components, that
is, scaffold, cells, and perfusion bioreactor systems. Finally, future challenges
for noninvasive imaging technologies are addressed.
PMID- 25116033
TI - New causes of central precocious puberty: the role of genetic factors.
AB - A pivotal event in the onset of puberty in humans is the reemergence of the
pulsatile release of the gonadotropin-releasing hormone (GnRH) from hypothalamic
neurons. Pathways governing GnRH ontogeny and physiology have been discovered by
studying animal models and humans with reproductive disorders. Recent human
studies implicated the activation of kisspeptin and its cognate receptor
(KISS1/KISS1R) and the inactivation of MKRN3 in the premature reactivation of
GnRH secretion, causing central precocious puberty (CPP). MKRN3, an imprinted
gene located on the long arm of chromosome 15, encodes makorin ring finger
protein 3, which is involved in ubiquitination and cell signaling. The MKRN3
protein is derived only from RNA transcribed from the paternally inherited copy
of the gene due to maternal imprinting. Currently, MKRN3 defects represent the
most frequent known genetic cause of familial CPP. In this review, we explored
the clinical, hormonal and genetic aspects of children with sporadic or familial
CPP caused by mutations in the kisspeptin and MKRN3 systems, essential genetic
factors for pubertal timing.
PMID- 25116034
TI - Therapeutic apheresis in Asia: An Indonesia single center experience.
AB - In developing countries, like Indonesia, apheresis is still a relative new
procedure. Nowadays, therapeutic apheresis procedures are performed in the field
of hematology and neurology, especially in the teaching hospitals in Indonesia.
Therapeutic apheresis procedure, that is, leukocytapheresis, therapeutic plasma
exchange (TPE), and thrombocytapheresis are already performed. In the period 2009
2013, 204 apheresis procedures in 137 patients to reduce the leukocytes, 72 TPE
procedures in 17 patients, and 14 thrombocyte reductions were performed in the
Sardjito hospital, Yogyakarta, Indonesia. In the future, to improve the
therapeutic apheresis implementation, it is important to increase the insurance
coverage and also should be considered to introduce the apheresis medicine into
the curriculum of appropriate physician programs in Indonesia. Especially in
Indonesia, a lot of efforts are still being needed to improve implementation of
therapeutic apheresis.
PMID- 25116035
TI - The relation of standardized mental health screening and categorical assessment
in detained male adolescents.
AB - Having an effective triage tool is an important step toward a careful use of the
restricted time and qualified personnel to perform comprehensive psychiatric
assessment in juvenile justice settings. The aims of this study were to examine
the construct validity of the Massachusetts Youth Screening Inventory-second
version (MAYSI-2), and its likelihood to identify youths who might have a
psychiatric disorder. Data from up to 781 male adolescents (mean age = 16.73
years) were gathered as part of the standardized mental health screening and
assessment in two all-male Youth Detention Centers in the Netherlands.
Categorical assessments were based on two structured diagnostic interviews.
Sensitivity, specificity, positive and negative predictive values, and the area
under the curve were calculated to evaluate the likelihood of the MAYSI-2 to
identify youths with a psychiatric disorder. Youths with a disorder scored
significantly higher on the corresponding MAYSI-2 subscale than youths without a
disorder. In the total sample, 70 % of the youths with a disorder met the Caution
cut-off criteria on at least one MAYSI-2 scale, while youths without a
psychiatric disorder were very unlikely to meet cut-off criteria for multiple
MAYSI-2 scales. Overall, the sensitivity was slightly better when analyses were
repeated in groups of youths from various ethnic origins. The findings supported
the construct validity of the Dutch MAYSI-2 and suggested that the MAYSI-2 is a
valid mental health screening tool that may serve relatively well as a triage
tool. Its effectiveness, however, may differ between ethnic groups.
PMID- 25116036
TI - Enrolment of children and adolescents in psychosocial care: more likely with low
family social support and poor parenting skills.
AB - Knowledge about determinants of child and adolescent enrolment in psychosocial
care concerns only single types of care and usually only socio-demographic
factors. The social environment is also a likely key determinant but evidence is
lacking. The aim of this study was to examine the associations between family
social support, parenting skills and child and adolescent enrolment in
psychosocial care. We obtained data on 1,331 children (response rate 56.6%), 4-18
years old, enrolled in preventive child health care, and child and adolescent
social care and mental health care because of psychosocial problems, and on 463
children (response rate 70.3%) not enrolled in psychosocial care. Results showed
that enrolment in psychosocial care was associated with low family social support
(odds ratio; 95%-confidence interval: 3.2; 2.4-4.4), and with poor parenting
skills, i.e. poor supervision (1.5; 1.1-2.1) and inconsistent disciplining (1.5;
1.1-2.1). Children's psychosocial problems partially mediated the associations
with family social support and completely with parenting skills. Children's
problems did not moderate the associations. Positive parenting was not associated
with care enrolment. We conclude that low family social support and poor
parenting are important factors associated with enrolment, in particular because
they are associated with more frequent occurrence of children's psychosocial
problems. This implies that professionals and policymakers need to be aware that
factors in children's social environment are related with enrolment in
psychosocial care, in addition to children's psychosocial problems.
PMID- 25116037
TI - Error-monitoring in an everyday task in people with Alzheimer-type dementia:
observations over five years of performance decline.
AB - Research suggests that, although everyday action errors increase significantly
with dementia progression, accomplishment of the task remains high, even in
severe dementia. We used archive observational data charting progressive decline
in everyday task performance to explore error-monitoring over a 5-year period in
four people with dementia. None of the participants showed effective error
monitoring during their execution of their established tea-making routine: Over 5
years and into more severe stages of dementia, errors increased, but there was no
reactive increase from our participants in error-monitoring. Training to error
monitor routine tasks may be an appropriate target for further study.
PMID- 25116038
TI - Publishing individual surgeons' death rates prompts risk averse behaviour.
PMID- 25116039
TI - Design considerations for electrode buffer layer materials in polymer solar
cells.
AB - Electrode buffer layers in polymer-based photovoltaic devices enable highly
efficient devices. In the absence of buffer layers, we show that diode
rectification is lost in ITO/P3HT:PCBM/Ag (ITO = indium tin oxide; P3HT = poly(3
hexylthiophene); PCBM = phenyl C61-butyric acid methyl ester) devices due to
nonselective charge injection through the percolated phase pathways of a bulk
heterojunction active layer. Charge-selective injection, and thus rectification
and device function, can be regained by placing thin, polymeric buffer layers
that break the direct electrode-active layer contact. Additionally, we show that
strong active layer-buffer layer interactions lead to unwanted vertical phase
separation and a kinked current-voltage curve. Device function is regained,
increasing power conversion efficiency from 3.6% to 7.2%, by placing a
noninteracting layer between the buffer and active layer. These results guide the
design and selection of future polymeric electrode buffer layers for efficient
polymer solar cell devices.
PMID- 25116042
TI - Positive selection of Wharton's jelly-derived CD105(+) cells by MACS technique
and their subsequent cultivation under suspension culture condition: A simple,
versatile culturing method to enhance the multipotentiality of mesenchymal stem
cells.
AB - OBJECTIVE: Wharton's jelly (WJ), an appropriate source of mesenchymal stem cells
(MSCs), has been shown to have a wide array of therapeutic applications. However,
the WJ-derived MSCs are very heterogeneous and have limited expression of
pluripotency markers. Hence, improvement of their culture condition would promote
the efficiency of WJ-MSCs. This study aims to employ a simple method of
cultivation to obtain WJ-MSCs which express more pluripotency markers. METHODS:
CD105(+) cells were separated by magnetic-associated (activated) cell sorting
from umbilical cord mucous tissue. CD105(+) cells were added to Methocult medium
diluted in alpha-minimum essential medium (alpha-MEM) and seeded in poly(2
hydroxyethyl methacrylate) (poly-HEMA)-coated plates for suspension culture
preparation. Differentiation capacity of isolated cells was evaluated in the
presence of differentiation-inducing media. The expression of pluripotency
markers such as Oct3/4, Nanog, and Sox2 was also analyzed by RT-PCR and western
blot techniques. Moreover, immunocytochemistry was performed to detect alpha
smooth muscle actin (antigene) (alpha-SMA) protein. RESULTS: WJ-MSCs grew
homogeneously and formed colonies when cultured under suspension culture
conditions (Non-adhesive WJ-MSCs). They maintained their growth ability in both
adherent and suspension cultures for several passages. Non-adhesive WJ-MSCs
expressed Oct3/4, Nanog, and Sox2 both at transcriptional and translational
levels in comparison to those cultured in conventional adherent cultures. They
also expressed alpha-SMA protein. DISCUSSION: In this study, we isolated WJ-MSCs
using a slightly modified culture condition. Our simple non-genetic method
resulted in a homogeneous population of WJ-MSCs, which highly expressed
pluripotency markers. CONCLUSION: In the future, more multipotent WJ-MSCs can be
harnessed as a non-embryonic source of MSCs in MSC-based cell therapy.
PMID- 25116043
TI - Why sigma-1 receptor dysfunction might confer vulnerability to cannabis-induced
psychosis.
PMID- 25116045
TI - Enhanced production of fatty alcohols by engineering the TAGs synthesis pathway
in Saccharomyces cerevisiae.
AB - The production of fatty acid-derived chemicals has received a great deal of
attention in recent years. In yeast cells, the main storage forms of fatty acids
are TAGs. However, the conversion of TAGs into fatty acid derivatives suffers
from a practical standpoint. Herein, a more direct strategy was applied to
accumulate cellular fatty acyl-CoAs in Saccharomyces cerevisiae, which are the
activated forms of fatty acids and used as important precursors for various
converting enzymes. The dga1 gene was deleted to block the fatty acyl-CoAs
dependent pathway of TAGs synthesis and a significant decrease in lipid content
was observed. The FAR gene was cloned and overexpressed in the wild type strain
and gene disrupted strain, to convert the fatty acyl-CoAs to the corresponding
fatty acid derivatives. The metabolic engineered pathway resulted in enhanced
production of fatty alcohols. Compared with the wild type strain with
overexpressed FAR gene, the yield of fatty alcohols in the Deltadga1 strain with
FAR was dramatically increased: the intracellular fatty alcohols increased from
26 mg/L to 45 mg/L, while the extracellular fatty alcohols increased from 2.2
mg/L to 4.3 mg/L. By optimizing the culture medium with increased carbon
concentration and limited nitrogen concentration, the fatty alcohols yield in the
Deltadga1 strain with FAR was further increased to 84 mg/L in cells and 14 mg/L
secreted in broth. The results in this study demonstrated the feasibility of
using the designed strategy to solve the bottleneck in utilizing TAGs for fatty
acid derivatives production.
PMID- 25116044
TI - Mitochondrial DNA from El Mirador cave (Atapuerca, Spain) reveals the
heterogeneity of Chalcolithic populations.
AB - Previous mitochondrial DNA analyses on ancient European remains have suggested
that the current distribution of haplogroup H was modeled by the expansion of the
Bell Beaker culture (ca 4,500-4,050 years BP) out of Iberia during the
Chalcolithic period. However, little is known on the genetic composition of
contemporaneous Iberian populations that do not carry the archaeological tool kit
defining this culture. Here we have retrieved mitochondrial DNA (mtDNA) sequences
from 19 individuals from a Chalcolithic sample from El Mirador cave in Spain,
dated to 4,760-4,200 years BP and we have analyzed the haplogroup composition in
the context of modern and ancient populations. Regarding extant African, Asian
and European populations, El Mirador shows affinities with Near Eastern groups.
In different analyses with other ancient samples, El Mirador clusters with Middle
and Late Neolithic populations from Germany, belonging to the Rossen, the
Salzmunde and the Baalberge archaeological cultures but not with contemporaneous
Bell Beakers. Our analyses support the existence of a common genetic signal
between Western and Central Europe during the Middle and Late Neolithic and
points to a heterogeneous genetic landscape among Chalcolithic groups.
PMID- 25116046
TI - Efficient optical extraction of hot-carrier energy.
AB - Light-induced generation of free charge carriers in semiconductors constitutes
the physical basis of photodetection and photovoltaics. To maximize its
efficiency, the energy of the photons must be entirely used for this purpose.
This is highly challenging owing to the ultrafast thermalization of 'hot'
carriers, which are created by absorption of high-energy photons. Thermalization
leads to heat generation, and hence efficiency loss. To circumvent this,
dedicated schemes such as photovoltaic hot-carrier cells are being explored. Here
we consider optical extraction of the excess energy of hot carriers by emission
of infrared photons, using erbium ions in combination with silicon nanocrystals.
We determine the external quantum yield of the infrared photon generation by the
erbium ions, and demonstrate that cooling of the hot carriers induces a steep,
step-like, increase in erbium-related external quantum yield by up to a factor of
15 towards higher excitation energies. Finally, we comment on the potential of
our findings for future photovoltaics in the form of an optical ultraviolet-to
infrared spectral converter.
PMID- 25116047
TI - The impact of a total hip replacement on jaw position, upper body posture and
body sway.
AB - OBJECTIVES: The purpose of this study was to examine whether, and to what extent,
a total hip replacement can influence the position and the movement of the jaw,
the upper body posture and body sway. METHODS: Twenty test subjects (6 females,
14 males) participated in this study pre- and post-total hip replacement, in
addition to a healthy control group of 20 subjects (5 females, 15 males). The
measurements were conducted by means of an ultrasound system to measure jaw
condyle position and movement of the lower jaw, a three-dimensional back scan to
analyze upper back posture, and a static and dynamic force plate to measure body
sway. For statistical analysis the Wilcoxon-Matched-Pairs-Test or Man-Whitney-U
Test, including a Bonferroni-Holm correction, respectively, was used. RESULTS:
After surgery, the mean values of the left and right jaw condyles of the test
group moved posterior, and the left condyle position was located more caudally.
There were no significant differences concerning the jaw position between the two
groups. There was little change in upper body posture in both groups. The test
group had a more anteriorly inclined thoracic spine and a less pronounced lumbar
lordosis. During static body sway measurements, increased fluctuations in the
test group after surgery could be seen. CONCLUSION: Differences between both
groups in the pre- and post-surgical condition could be detected. These
differences were more prominent when the measured body segments were more
distally located with respect to the hip region.
PMID- 25116048
TI - Hemoglobin and hematocrit levels in the prediction of complicated Crohn's disease
behavior--a cohort study.
AB - BACKGROUND: Markers that predict the occurrence of a complicated disease behavior
in patients with Crohn's disease (CD) can permit a more aggressive therapeutic
regimen for patients at risk. The aim of this cohort study was to test the blood
levels of hemoglobin (Hgb) and hematocrit (Hct) for the prediction of complicated
CD behavior and CD related surgery in an adult patient population. METHODS: Blood
samples of 62 CD patients of the German Inflammatory Bowel Disease-network
"Kompetenznetz CED" were tested for the levels of Hgb and Hct prior to the
occurrence of complicated disease behavior or CD related surgery. The relation of
these markers and clinical events was studied using Kaplan-Meier survival
analysis and adjusted COX-proportional hazard regression models. RESULTS: The
median follow-up time was 55.8 months. Of the 62 CD patients without any previous
complication or surgery 34% developed a complication and/or underwent CD related
surgery. Low Hgb or Hct levels were independent predictors of a shorter time to
occurrence of the first complication or CD related surgery. This was true for
early as well as late occurring complications. Stable low Hgb or Hct during
serial follow-up measurements had a higher frequency of complications compared to
patients with a stable normal Hgb or Hct, respectively. CONCLUSIONS:
Determination of Hgb or Hct in complication and surgery naive CD patients might
serve as an additional tool for the prediction of complicated disease behavior.
PMID- 25116049
TI - [Imaging of blunt chest trauma].
AB - CLINICAL/METHODOLOGICAL ISSUE: Blunt chest trauma is associated with high
morbidity and mortality. Consequently, all patients should be evaluated
radiologically after blunt chest trauma to allow timely and appropriate
treatment. STANDARD RADIOLOGICAL METHODS: Conventional chest radiographs and
computed tomography (CT) are proven modalities with which to evaluate patients
after blunt chest trauma. METHODOLOGICAL INNOVATIONS: Over the last several years
extended focused assessment with sonography for trauma (eFAST) has gained
increasing importance for the initial assessment of seriously injured patients.
PRACTICAL RECOMMENDATIONS: In the acute phase of severely injured patients eFAST
examinations are helpful to exclude pneumothorax, hemothorax and hemopericardium.
Chest radiographs may also be used to diagnose a pneumothorax or hemothorax;
however, the sensitivity is limited and CT is the diagnostic modality of choice
to evaluate severely injured patients.
PMID- 25116051
TI - Periodic fluorescent silver clusters assembled by rolling circle amplification
and their sensor application.
AB - A simple method for preparing DNA-stabilized Ag nanoclusters (NCs) nanowires is
presented. To fabricate the Ag NCs nanowires, we use just two unmodified
component strands and a long enzymatically produced scaffold. These nanowires
form at room temperature and have periodic sequence units that are available for
fluorescence Ag NCs assembled which formed three-way junction (TWJ) structure.
These Ag NCs nanowires can be clearly visualized by confocal microscopy.
Furthermore, due to the high efficiency of rolling circle amplification reaction
in signal amplification, the nanowires exhibit high sensitivity for the specific
DNA detection with a wide linear range from 6 to 300 pM and a low detection limit
of 0.84 pM, which shows good performance in the complex serum samples. Therefore,
these Ag NCs nanowires might have great potential in clinical and imaging
applications in the future.
PMID- 25116052
TI - N-terminomics and proteogenomics, getting off to a good start.
AB - Proteogenomics consists of the annotation or reannotation of protein-coding
nucleic acid sequences based on the empirical observation of their gene products.
While functional annotation of predicted genes is increasingly feasible given the
multiplicity of genomes available for many branches of the tree of life, the
accurate annotation of the translational start sites is still a point of
contention. Extensive coverage of the proteome, including specifically the N
termini, is now possible, thanks to next-generation mass spectrometers able to
record data from thousands of proteins at once. Efforts to increase the peptide
coverage of protein sequences and to detect low abundance proteins are important
to make proteomic and proteogenomic studies more comprehensive. In this review,
we present the panoply of N-terminus-oriented strategies that have been developed
over the last decade.
PMID- 25116050
TI - Dietary isoflavones and bone mineral density during midlife and the menopausal
transition: cross-sectional and longitudinal results from the Study of Women's
Health Across the Nation Phytoestrogen Study.
AB - OBJECTIVE: This study aims to examine cross-sectional and longitudinal relations
between dietary intake of isoflavones and bone mineral density (BMD) at the
lumbar spine (LS) and femoral neck (FN) in black, white, Chinese, and Japanese
women during the menopausal transition. METHODS: We tested whether tertiles of
isoflavone intake were associated with baseline BMD when all women were
premenopausal or early perimenopausal. To analyze whether isoflavone intake was
associated with longitudinal BMD, we fitted piecewise linear models to repeated
measurements of baseline-normalized LS or FN BMD as functions of time before or
after the final menstrual period (FMP) date. RESULTS: Multiply adjusted mean FN
BMD values of premenopausal Japanese women were monotonically positively related
to isoflavone consumption (P for trend = 0.0003). Otherwise, no statistically
significant baseline associations were observed. During the period of 1 year
before the FMP through 5 years after the FMP, all participants lost LS and FN
BMD. Loss was unrelated to isoflavone intake, except for Japanese women during
the period of 1 year before the FMP to 2 years after the FMP: higher tertiles of
isoflavone intake were associated with greater annual LS BMD loss rates (P for
trend = 0.01) and FN loss rates (P for trend = 0.04). CONCLUSIONS: In Japanese
women, higher isoflavone intake is associated with higher peak FN BMD but also
with greater rates of LS and FN BMD loss during the menopausal transition.
Results for the other racial/ethnic groups did not support a relation between
dietary intake of isoflavones and either peak BMD or BMD loss during the
menopausal transition.
PMID- 25116053
TI - Thermal adaptation of alpha-amylases: a review.
AB - The temperature adaptation of alpha-amylase can be gained by different
adjustments in protein structure with consecutive effects on the stability and
flexibility of the protein. In this review, meso, thermo and cold-active alpha
amylases have been compared with respect to their structure and intramolecular
interactions. With decrease in temperature, the number of ionic interactions also
decreases, leading to greater flexibility of proteins. It has also been observed
that the proline and arginine content is higher in thermophilic amylases as
compared to meso and psychrophilic amylases, increasing the rigidity and
structural stability of protein molecule.
PMID- 25116054
TI - The TrmB family: a versatile group of transcriptional regulators in Archaea.
AB - Microbes are organisms which are well adapted to their habitat. Their survival
depends on the regulation of gene expression levels in response to environmental
signals. The most important step in regulation of gene expression takes place at
the transcriptional level. This regulation is intriguing in Archaea because the
eu-karyotic-like transcription apparatus is modulated by bacterial-like
transcription regulators. The transcriptional regulator of mal operon (TrmB)
family is well known as a very large group of regulators in Archaea with more
than 250 members to date. One special feature of these regulators is that some of
them can act as repressor, some as activator and others as both repressor and
activator. This review gives a short updated overview of the TrmB family and
their regulatory patterns in different Archaea as a lot of new data have been
published on this topic since the last review from 2008.
PMID- 25116055
TI - Acidibacter ferrireducens gen. nov., sp. nov.: an acidophilic ferric iron
reducing gammaproteobacterium.
AB - An acidophilic gammaproteobacterium, isolated from a pit lake at an abandoned
metal mine in south-west Spain, was shown to be distantly related to all
characterized prokaryotes, and to be the first representative of a novel genus
and species. Isolate MCF85 is a Gram-negative, non-motile, rod-shaped mesophilic
bacterium with a temperature growth optimum of 32-35 degrees C (range 8-45
degrees C). It was categorized as a moderate acidophile, growing optimally at pH
3.5-4.0 and between pH 2.5 and 4.5. Under optimum conditions its culture doubling
time was around 75 min. Only organic electron donors were used by MCF85, and the
isolate was confirmed to be an obligate heterotroph. It grew on a limited range
of sugars (hexoses and disaccharides, though not pentoses) and some other small
molecular weight organic compounds, and growth was partially or completely
inhibited by small concentrations of some aliphatic acids. The acidophile grew in
the presence of >100 mM ferrous iron or aluminium, but was more sensitive to some
other metals, such as copper. It was also much more tolerant of arsenic (V) than
arsenic (III). Isolate MCF85 catalysed the reductive dissolution of the ferric
iron mineral schwertmannite when incubated under micro-aerobic or anaerobic
conditions, causing the culture media pH to increase. There was no evidence,
however, that the acidophile could grow by ferric iron respiration under strictly
anoxic conditions. Isolate MCF85 is the designated type strain of the novel
species Acidibacter ferrireducens (=DSM 27237(T) = NCCB 100460(T)).
PMID- 25116056
TI - Picophytoplankton predominance in hypersaline lakes (Transylvanian Basin,
Romania).
AB - The occurrence and importance of photoautotrophic picoplankton (PPP, cells with a
diameter <2 MUm) was studied along a trophic and salinity gradient in hypersaline
lakes of the Transylvanian Basin (Romania). The studied lakes were found to be
rich in PPP, with abundances (maximum 7.6 * 10(6) cells mL(-1)) higher than in
freshwater and marine environments of similar trophic conditions. The
contribution of PPP to the total phytoplankton biovolume did not decrease with
increasing trophic state as it was generally found in other aquatic environments.
Regardless of the trophic conditions, the contribution of PPP could reach 90-100
% in these hypersaline lakes. We hypothesized that the PPP predominance might be
the result of the low grazing pressure, since heterotrophic nanoflagellates (the
main grazers of PPP) were absent in the studied samples. There were significant
differences in community composition among the lakes along the salinity gradient.
CyPPP predominated in less saline waters (mainly below 5 %), while EuPPP were
present along the entire salinity range (up to 18.7 %), dominating the
phytoplankton between 3 and 13 % salinity. Above 13 % salinity, the phytoplankton
was composed mainly of Dunaliella species.
PMID- 25116057
TI - Early paternal deprivation alters levels of hippocampal brain-derived
neurotrophic factor and glucocorticoid receptor and serum corticosterone and
adrenocorticotropin in a sex-specific way in socially monogamous mandarin voles.
AB - In monogamous mammals, fathers play an important role in the development of the
brain and typical behavior in offspring, but the exact nature of this process is
not well understood. In particular, little research has addressed whether the
presence or absence of paternal care alters levels of hippocampal glucocorticoid
receptor (GR) and brain-derived neurotrophic factor (BDNF), and basal levels of
serum corticosterone (CORT) and adrenocorticotropin (ACTH). Here, we explored
this concept using socially monogamous mandarin voles (Microtus mandarinus), a
species in which fathers display high levels of paternal care toward their pups.
Our immunohistochemical study shows that paternal deprivation (PD) significantly
decreased levels of GR and BDNF protein in the CA1 and CA2/3 of the hippocampus.
In the dental gyrus, decreases in GR and BDNF induced by PD were evident in
females but not in males. Additionally, enzyme-linked immunosorbent assay results
show that PD significantly upregulated levels of serum CORT and ACTH in females,
but not males. These findings demonstrate that PD alters HPA axis activity in a
sex-specific way. The changes in stress hormones documented here may be
associated with alteration in hippocampal BDNF and GR levels.
PMID- 25116058
TI - Posture variation among office workers when using different information and
communication technologies at work and away from work.
AB - Office workers perform tasks using different information and communication
technologies (ICT) involving various postures. Adequate variation in postures and
muscle activity is generally believed to protect against musculoskeletal
complaints, but insufficient information exists regarding the effect on postural
variation of using different ICT. Thus, this study among office workers aimed to
determine and compare postures and postural variation associated with using
distinct types of ICT. Upper arm, head and trunk postures of 24 office workers
were measured with the Physiometer over a whole day in their natural work and
away-from-work environments. Postural variation was quantified using two indices:
APDF(90-10) and EVA(sd). Various ICT had different postural means and variation.
Paper-based tasks had more non-neutral, yet also more variable postures.
Electronics-based tasks had more neutral postures, with less postural
variability. Tasks simultaneously using paper- and electronics-based ICT had
least neutral and least variable postures. Tasks without ICT usually had the most
posture variability. Interspersing tasks involving different ICT could increase
overall exposure variation among office workers and may thus contribute to
musculoskeletal risk reduction.
PMID- 25116064
TI - Fluorinated graphene and hexagonal boron nitride as ALD seed layers for graphene
based van der Waals heterostructures.
AB - Ultrathin dielectric materials prepared by atomic-layer-deposition (ALD)
technology are commonly used in graphene electronics. Using the first-principles
density functional theory calculations with van der Waals (vdW) interactions
included, we demonstrate that single-side fluorinated graphene (SFG) and
hexagonal boron nitride (h-BN) exhibit large physical adsorption energy and
strong electrostatic interactions with H2O-based ALD precursors, indicating their
potential as the ALD seed layer for dielectric growth on graphene. In graphene
SFG vdW heterostructures, graphene is n-doped after ALD precursor adsorption on
the SFG surface caused by vertical intrinsic polarization of SFG. However,
graphene-h-BN vdW heterostructures help preserving the intrinsic characteristics
of the underlying graphene due to in-plane intrinsic polarization of h-BN. By
choosing SFG or BN as the ALD seed layer on the basis of actual device design
needs, the graphene vdW heterostructures may find applications in low-dimensional
electronics.
PMID- 25116065
TI - [Ocular myopathies and autoimmunity].
PMID- 25116066
TI - [Clinical diagnostics for the tear film and the ocular surface].
PMID- 25116067
TI - Rectal cancer seen over 30 years.
PMID- 25116072
TI - Enhanced thermal oxidation stability of reduced graphene oxide by nitrogen
doping.
AB - Nitrogen-doped reduced graphene oxide (N-doped RGO) samples with a high level of
doping, up to 13 wt. %, have been prepared by annealing graphene oxide under a
flow of pure ammonia. The presence of nitrogen within the structure of RGO
induces a remarkable increase in the thermal stability against oxidation by air.
The thermal stability is closely related with the temperature of synthesis and
the nitrogen content. The combustion reaction of nitrogen in different
coordination environments (pyridinic, pyrrolic, and graphitic) is analyzed
against a graphene fragment (undoped) from a thermodynamic point of view. In
agreement with the experimental observations, the combustion of undoped graphene
turns out to be more spontaneous than when nitrogen atoms are present.
PMID- 25116074
TI - Electro-responsively reversible transition of polythiophene films from
superhydrophobicity to superhydrophilicity.
AB - An electro-responsively reversible switching of wettability between
superhydrophobicity and superhydrophilicity has been obtained from a highly
porous structured polythiophene film. The polythiophene film was prepared by two
step electrochemical deposition on an indium tin oxide (ITO) substrate. The
underlying poly(3,4-ethylenedioxythiophene) (PEDOT) provides a highly porous
structured conductive support, and poly(3-methylthiophene) (P(3-MTH)) deposited
thereon plays the role of a low-surface-energy conductive coating. The
wettability switching of this double-layer film between superhydrophobicity and
superhydrophilicity has been investigated by doping and dedoping in an
electrolyte solution containing ClO4(-). Electrochromism of the film was also
seen to accompany the electrochemical process of conversion between the two
superwetting states. On the basis of this porous electro-active film, an in situ
electro-wetting device was also demonstrated.
PMID- 25116073
TI - Early plasma exchange for treating ricin toxicity in children after castor bean
ingestion.
AB - Plasma exchange (PE) for the treatment of ricin toxicity has not been previously
reported. Here we describe the use of PE to treat children who experienced ricin
toxicity after ingesting castor beans. Seven children (median age: 8.1 years) who
consumed castor beans (median: 5 beans) were treated with PE. All had bradycardia
and sinus arrhythmia, and most had experienced episodes of vomiting and/or
diarrhea. PE settings were blood flow, 50-80 mL/min; PE rate, 600-800 mL/h;
volume of exchange, 1440-1950 mL. Median time from ingestion to PE was 73 h. All
clinical symptoms disappeared and vital signs rapidly returned to normal after
PE; no severe organ dysfunction occurred. All children were discharged and
recovered uneventfully. Concentrations of all serum biochemical parameters
significantly decreased immediately after PE. Some, but not all, of these
parameters were also significantly decreased at 48 and 72 h after PE compared
with before PE. Our findings suggest that PE can be an effective early
intervention in the treatment of ricin toxicity due to castor bean ingestion.
PMID- 25116075
TI - Allowing brief delays in responding improves event-based prospective memory for
young adults living with HIV disease.
AB - Event-based prospective memory (PM) tasks require individuals to remember to
perform an action when they encounter a specific cue in the environment, and they
have clear relevance for daily functioning for individuals with HIV. In many
everyday tasks, not only must the individual maintain the intent to perform the
PM task, but the PM task response also competes with the alternative and more
habitual task response. The current study examined whether event-based PM can be
improved by slowing down the pace of the task environment. Fifty-seven young
adults living with HIV performed an ongoing lexical decision task while
simultaneously performing a PM task of monitoring for a specific word (which was
focal to the ongoing task of making lexical decisions) or syllable contained in a
word (which was nonfocal). Participants were instructed to refrain from making
task responses until after a tone was presented, which occurred at varying onsets
(0-1600 ms) after each stimulus appeared. Improvements in focal and nonfocal PM
accuracy were observed with response delays of 600 ms. Furthermore, the
difference in PM accuracy between the low-demand focal PM task and the resource
demanding nonfocal PM task was reduced by half across increasingly longer delays,
falling from 31% at 0-ms delay to only 14% at 1600-ms delay. The degree of
ongoing task response slowing for the PM conditions, relative to a control
condition that did not have a PM task and made lexical decisions only, also
decreased with increased delay. Overall, the evidence indicates that delaying the
task responses of younger HIV-infected adults increased the probability that the
PM relevant features of task stimuli were adequately assessed prior to the
ongoing task response, and by implication that younger HIV infected adults can
more adequately achieve PM goals when the pace of the task environment is slowed
down.
PMID- 25116077
TI - Inhibition of neointimal hyperplasia in rats treated with atorvastatin after
carotid artery injury may be mainly associated with down-regulation of survivin
and Fas expression.
AB - CONTEXT: Atorvastatin is a member of the drug class known as statins, which is
used for lowering blood cholesterol. OBJECTIVE: The present study investigates
the effect and mechanism of atorvastatin on neointimal hyperplasia after carotid
artery injury (CAI) of rat. MATERIALS AND METHODS: Fifty male rats were randomly
divided into four groups: control group, sham-operated group, model group, and
atorvastatin treatment group. The treatment group was fed with atorvastatin (10
mg/kg) with gastro-gavage at 5 p.m. every day for 28 d after surgery. The control
group, model group, and sham-operated group were fed with the same volume of
distilled water instead. The proliferations of intimal and medial layers were
evaluated by hematoxylin & eosin (H&E) staining. The apoptosis of vascular smooth
muscle cells (VSMCs) was determined by terminal deoxynucleotidyl transferased UTP
nick end labeling (TUNEL) staining. Plasma concentrations of survivin and sFas
were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Atorvastatin
reduced neointimal formation and increased apoptosis of VSMCs in neointima. VSMCs
apoptosis emerged at 3 d (8.42 +/- 0.449 MUm) and the intimal proliferation
peaked by the end of 14 d (41.58 +/- 1.64 MUm). The plasma levels of survivin and
sFas were gradually increased with the neointimal hyperplasia and increasingly
decreased after atorvastatin treatment. The plasma levels of survivin and sFas in
rats were elevated at 3 d (464.80 +/- 105.27 pg/ml and 3256.00 +/- 478.20 pg/ml,
respectively), reached the peak of survivin at 14 d (1089.20 +/- 232.32 pg/ml)
and sFas at 7 d (4362.00 +/- 639.92 pg/ml) and decreased at 28 d (562.00 +/-
90.11 pg/ml and 2148.00 +/- 257.14 pg/ml, respectively) in the model group.
Compared with the model group, the atorvastatin treatment group has significantly
less neointimal hyperplasia and more apoptosis of VSMCs. CONCLUSIONS:
Atorvastatin can inhibit neointimal hyperplasia and promote SMCs apoptosis in
neointimal layers, which may be mainly associated with down-regulation of
survivin and Fas expression after CAI of rat.
PMID- 25116078
TI - Covalent binding of 4-hydroxynonenal to matrix metalloproteinase 13 studied by
liquid chromatography-mass spectrometry.
AB - Osteoarthritis (OA) is caused by the degradation of articular cartilage and
affects approximately 80% of people over the age of 65. Matrix metalloproteinases
(MMPs) belong to a group of zinc endopeptidases that degrade extracellular matrix
(ECM) proteins in cartilage. MMP-13, also known as collagenase 3, cleaves type II
collagen more rapidly than other MMPs and therefore is an important target for
the treatment of OA. The lipid peroxidation product 4-hydroxy-2-(E)-nonenal
(HNE), generated under oxidative stress, is known to play a crucial role in
cartilage degradation; however, the mechanism is not yet fully understood. An
approach has been developed to monitor HNE modification sites by incubating rhMMP
13 +/- HNE in vitro followed by analysis of tryptic digests by UHPLC coupled to
high resolution (HR) quadrupole-time-of-flight (QqTOF) tandem mass spectrometry
(MS/MS). The analysis elucidated several covalently modified histidine and
cysteine residues. The reaction was monitored using different HNE concentrations
and incubation times. A targeted assay, using multiple-reaction monitoring (MRM),
was then optimized to increase the sensitivity of detecting these modification
sites in biological samples. HNE-related covalent modifications of MMP-13 were
confirmed in enriched extracts from interleukin 1beta-activated chondrocytes from
OA patients using HR-MS/MS and MRM analysis.
PMID- 25116076
TI - Exploring the influence of the protein environment on metal-binding
pharmacophores.
AB - The binding of a series of metal-binding pharmacophores (MBPs) related to the
ligand 1-hydroxypyridine-2-(1H)-thione (1,2-HOPTO) in the active site of human
carbonic anhydrase II (hCAII) has been investigated. The presence and/or position
of a single methyl substituent drastically alters inhibitor potency and can
result in coordination modes not observed in small-molecule model complexes. It
is shown that this unexpected binding mode is the result of a steric clash
between the methyl group and a highly ordered water network in the active site
that is further stabilized by the formation of a hydrogen bond and favorable
hydrophobic contacts. The affinity of MBPs is dependent on a large number of
factors including donor atom identity, orientation, electrostatics, and van der
Waals interactions. These results suggest that metal coordination by
metalloenzyme inhibitors is a malleable interaction and that it is thus more
appropriate to consider the metal-binding motif of these inhibitors as a
pharmacophore rather than a "chelator". The rational design of inhibitors
targeting metalloenzymes will benefit greatly from a deeper understanding of the
interplay between the variety of forces governing the binding of MBPs to active
site metal ions.
PMID- 25116079
TI - Large-scale avian influenza surveillance in wild birds throughout the United
States.
AB - Avian influenza is a viral disease that primarily infects wild and domestic
birds, but it also can be transmitted to a variety of mammals. In 2006, the
United States of America Departments of Agriculture and Interior designed a large
scale, interagency surveillance effort that sought to determine if highly
pathogenic avian influenza viruses were present in wild bird populations within
the United States of America. This program, combined with the Canadian and
Mexican surveillance programs, represented the largest, coordinated wildlife
disease surveillance program ever implemented. Here we analyze data from 197,885
samples that were collected from over 200 wild bird species. While the initial
motivation for surveillance focused on highly pathogenic avian influenza, the
scale of the data provided unprecedented information on the ecology of avian
influenza viruses in the United States, avian influenza virus host associations,
and avian influenza prevalence in wild birds over time. Ultimately, significant
advances in our knowledge of avian influenza will depend on both large-scale
surveillance efforts and on focused research studies.
PMID- 25116081
TI - The impact of Universal Health Coverage on health care consumption and risky
behaviours: evidence from Thailand.
AB - Thailand is among the first non-OECD countries to have introduced a form of
Universal Health Coverage (UHC). This policy represents a natural experiment to
evaluate the effects of public health insurance on health behaviours. In this
paper, we examine the impact of Thailand's UHC programme on preventive
activities, unhealthy or risky behaviours and health care consumption using data
from the Thai Health and Welfare Survey. We use doubly robust estimators that
combine propensity scores and linear regressions to estimate differences-in
differences (DD) and differences-in-DD models. Our results offer important
insights. First, UHC increases individuals' likelihood of having an annual check
up, especially among women. Regarding health care consumption, we observe that
UHC increases hospital admissions by over 2% and increases outpatient visits by
13%. However, there is no evidence that UHC leads to an increase in unhealthy
behaviours or a reduction of preventive efforts. In other words, we find no
evidence of ex ante moral hazard. Overall, these findings suggest positive health
impacts among the Thai population covered by UHC.
PMID- 25116080
TI - Long-distance wind-dispersal of spores in a fungal plant pathogen: estimation of
anisotropic dispersal kernels from an extensive field experiment.
AB - Given its biological significance, determining the dispersal kernel (i.e., the
distribution of dispersal distances) of spore-producing pathogens is essential.
Here, we report two field experiments designed to measure disease gradients
caused by sexually- and asexually-produced spores of the wind-dispersed banana
plant fungus Mycosphaerella fijiensis. Gradients were measured during a single
generation and over 272 traps installed up to 1000 m along eight directions
radiating from a traceable source of inoculum composed of fungicide-resistant
strains. We adjusted several kernels differing in the shape of their tail and
tested for two types of anisotropy. Contrasting dispersal kernels were observed
between the two types of spores. For sexual spores (ascospores), we characterized
both a steep gradient in the first few metres in all directions and rare long
distance dispersal (LDD) events up to 1000 m from the source in two directions. A
heavy-tailed kernel best fitted the disease gradient. Although ascospores
distributed evenly in all directions, average dispersal distance was greater in
two different directions without obvious correlation with wind patterns. For
asexual spores (conidia), few dispersal events occurred outside of the source
plot. A gradient up to 12.5 m from the source was observed in one direction only.
Accordingly, a thin-tailed kernel best fitted the disease gradient, and
anisotropy in both density and distance was correlated with averaged daily wind
gust. We discuss the validity of our results as well as their implications in
terms of disease diffusion and management strategy.
PMID- 25116082
TI - Association between interleukin-10 promoter gene polymorphisms and acute graft
versus-host disease after hematopoietic stem cell transplantation: a systematic
review and meta-analysis.
AB - OBJECTIVES: Interleukin-10 (IL-10) is an important immunomodulatory cytokine. The
association between IL-10 promoter gene polymorphisms and acute graft-versus-host
disease (aGVHD) risk is established; however, results of these studies remain
inconclusive. We performed a meta-analysis to clarify the effects of IL-10
promoter gene polymorphisms on aGVHD risk. METHODS: The authors searched MEDLINE,
EMBASE, and Cochrane Library databases. Two independent authors extracted data,
and the effects were estimated from an odds ratio (OR) with 95% confidence
intervals (CIs). Subgroup and sensitivity analyses identified sources of
heterogeneity. RESULTS: Finally, a total of 11 studies encompassing 3588
recipients and 3221 donors were included to study IL-10 -1082 G > A, -819 C > T,
and -592 C > A polymorphisms. IL-10 -819 CC genotype was associated with an
increased aGVHD risk (grade I-IV: OR, 2.722 (95% CI, 1.360-5.450); grade II-IV:
OR, 2.265 (95% CI, 1.015-5.053)). Furthermore, patients who received grafts from
donors with an IL-10 -819 CC genotype experienced more frequent grade I-IV aGVHD
(OR, 2.306 (95% CI, 1.168-4.551)). Recipients with IL-10 -592 CC genotypes were
at increased risk for grade II-IV aGVHD (OR, 1.999 (95% CI, 1.230-3.250)).
Together, this meta-analysis found that IL-10 -819 CC and -592 CC polymorphisms
increased aGVHD risk. DISCUSSION AND CONCLUSION: This meta-analysis found the
evidence that the IL-10 -819 CC and -592 CC genotypes in both recipients and
donors increased the risk of aGVHD in allogeneic hematopoietic stem cell
transplantation (HSCT) patients. These results contribute towards improving
patient outcome through insight and rationale for individualized treatment
strategies considering genetic determinants.
PMID- 25116083
TI - Production of recombinant proteins in microalgae at pilot greenhouse scale.
AB - Recombinant protein production in microalgae chloroplasts can provide correctly
folded proteins in significant quantities and potentially inexpensive costs
compared to other heterologous protein production platforms. The best results
have been achieved by using the psbA promoter and 5' untranslated region (UTR) to
drive the expression of heterologous genes in a psbA-deficient, non
photosynthetic, algal host. Unfortunately, using such a strategy makes the system
unviable for large scale cultivation using natural sunlight for photosynthetic
growth. In this study we characterized eight different combinations of 5'
regulatory regions and psbA coding sequences for their ability to restore
photosynthesis in a psbA-deficient Chlamydomonas reinhardtii, while maintaining
robust accumulation of a commercially viable recombinant protein driven by the
psbA promoter/5'UTR. The recombinant protein corresponded to bovine Milk Amyloid
A (MAA), which is present in milk colostrum and could be used to prevent
infectious diarrhea in mammals. This approach allowed us to identify
photosynthetic strains that achieved constitutive production of MAA when grown
photosynthetically in 100 L bags in a greenhouse. Under these conditions, the
maximum MAA expression achieved was 1.86% of total protein, which corresponded to
3.28 mg/L of culture medium. Within our knowledge, this is the first report of a
recombinant protein being produced this way in microalgae.
PMID- 25116084
TI - Physical activity level and incident type 2 diabetes among Chinese adults.
AB - PURPOSE: The objective is to examine the association between physical activity
level (PAL) and incident type 2 diabetes among middle-age and older Chinese men
and women in urban China. METHODS: This prospective study included 6348
participants (age 35 to 74 yr) who were free of diabetes and cardiovascular
disease at baseline. PAL was estimated on the basis of self-reported overall
physical activity on a typical day. According to PAL, participants were
classified into four groups: sedentary (PAL, 1.00-1.39), low active (PAL, 1.40
1.59), active (PAL, 1.60-1.89), and very active (PAL, >1.89). The association of
PAL with incident diabetes was examined by Cox proportional hazards model.
RESULTS: During 7.9 yr of follow-up (50,293 person-years), 478 incident cases of
type 2 diabetes were identified. After adjustment for age, sex, geographic
region, educational level, smoking, alcohol use, and family history of diabetes,
the HR (95% CI) values for type 2 diabetes across increasing categories of PAL
were 1.00 (reference), 0.82 (0.62-1.09), 0.63 (0.47-0.83), and 0.47 (0.36-0.61),
respectively (P for trend <0.0001). Additional adjustment for baseline body mass
index or waist circumference attenuated the magnitude of risk reduction, but it
remained significant. The inverse association between PAL and risk of incident
diabetes was persistent in subgroup analyses according to age, sex, hypertension,
smoking, body mass index, waist circumference, and fasting plasma glucose level.
CONCLUSIONS: Higher PAL is associated with substantial reduction in risk of type
2 diabetes. Our findings suggest the importance of a physically active lifestyle
in the prevention of diabetes.
PMID- 25116085
TI - The effects of inspiratory muscle training in older adults.
AB - PURPOSE: Declining inspiratory muscle function and structure and systemic low
level inflammation and oxidative stress may contribute to morbidity and mortality
during normal ageing. Therefore, we examined the effects of inspiratory muscle
training (IMT) in older adults on inspiratory muscle function and structure and
systemic inflammation and oxidative stress, and reexamined the reported positive
effects of IMT on respiratory muscle strength, inspiratory muscle endurance,
spirometry, exercise performance, physical activity levels (PAL), and quality of
life (QoL). METHODS: Thirty-four healthy older adults (68 +/- 3 yr) with normal
spirometry, respiratory muscle strength, and physical fitness were divided
equally into a pressure-threshold IMT or sham-hypoxic placebo group. Before and
after an 8-wk intervention, measurements were taken for dynamic inspiratory
muscle function and inspiratory muscle endurance using a weighted plunger
pressure-threshold loading device; diaphragm thickness by using B-mode
ultrasonography; plasma cytokine concentrations by using immunoassays; DNA damage
levels in peripheral blood mononuclear cells by using comet assays; spirometry,
maximal mouth pressures, and exercise performance by using a 6-min walk test; PAL
by using a questionnaire and accelerometry; and QoL using a questionnaire.
RESULTS: Compared with placebo, IMT increased maximal inspiratory pressure (+34%
+/- 43%, P = 0.008), diaphragm thickness at residual volume (+38% +/- 39%, P =
0.03), and peak inspiratory flow (+35% +/- 42%, P = 0.049) but did not change
other spirometry measures, plasma cytokine concentrations, DNA damage levels in
peripheral blood mononuclear cells, dynamic inspiratory muscle function,
inspiratory muscle endurance, exercise performance, PAL, or QoL. CONCLUSION:
These novel data indicate that in healthy older adults, IMT elicits some positive
changes in inspiratory muscle function and structure but neither attenuates
systemic inflammation and oxidative stress nor improves exercise performance,
PAL, or QoL.
PMID- 25116087
TI - Muscle fascicle behavior during eccentric cycling and its relation to muscle
soreness.
AB - A single bout of eccentric exercise confers a protective effect against muscle
damage and soreness in subsequent eccentric exercise bouts, but the mechanisms
underpinning this effect are unclear. PURPOSE: This study compared vastus
lateralis (VL) muscle-tendon behavior between two eccentric cycling bouts to test
the hypothesis that muscle-tendon behavior would be different between bouts and
would be associated with the protective effect. METHODS: Eleven untrained men
(27.1 +/- 7.0 yr) performed two bouts of eccentric cycling (ECC1 and ECC2)
separated by 2 wk for 10 min at 65% of maximal concentric workload (191.9 +/-
44.2 W) each. Muscle soreness (by visual analog scale) and maximal voluntary
isometric contraction (MVC) torque of the knee extensors were assessed before and
1-2 d after exercise. Using ultrasonography, VL fascicle length and angle changes
during cycling were assessed, and tendinous tissue (TT) length changes were
estimated. VL EMG amplitude, crank torque, and knee joint angles were measured
during cycling. RESULTS: Soreness was greater (P < 0.0001) after ECC1 than ECC2,
although MVC changes were not different between bouts (P = 0.47). No significant
differences in peak EMG amplitude (normalized to EMG during MVC), crank peak
torque, or knee angles were evident between bouts. However, fascicle elongation
was 16% less during ECC2 than ECC1 (P < 0.01), indicating less fascicle strain in
ECC2. Maximum TT length occurred at a smaller knee joint angle during ECC2 than
ECC1 (P = 0.055). CONCLUSION: These results suggest that a lesser fascicle
elongation and earlier TT elongation were associated with reduced muscle soreness
after ECC2 than ECC1; thus, changes in muscle-tendon behavior may be an important
mechanism underpinning the protective effect.
PMID- 25116086
TI - Physical activity and chronic prostatitis/chronic pelvic pain syndrome.
AB - PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a
prevalent urologic disorder among men, but its etiology is still poorly
understood. Our objective was to examine the relation between physical activity
and incidence of CP/CPPS in a large cohort of male health professionals. METHODS:
We conducted a prospective cohort study among men in the Health Professionals
Follow-up Study followed from 1986 to 2008. The study population included 20,918
men who completed all CP/CPPS questions on the 2008 questionnaire. Leisure-time
physical activity, including type and intensity of activity, was measured by
questionnaire in 1986. A National Institute of Health Chronic Prostatitis Symptom
Index pain score was calculated on the basis of the responses on the 2008
questionnaire. Participants with pain scores >=8 were considered CP/CPPS cases (n
= 689). RESULTS: Higher leisure-time physical activity was associated with lower
risk of CP/CPPS. The multivariable-adjusted odds ratio comparing >35.0 to <=3.5
MET.h.wk of physical activity was 0.72 (95% confidence interval, 0.56-0.92; P for
trend <0.001). Observed inverse associations between physical activity and
CP/CPPS were similar for both moderate- and vigorous-intensity activities.
Sedentary behavior, measured as time spent watching television, was not
associated with risk of CP/CPPS (P for trend = 0.64). CONCLUSIONS: Findings from
this study, the first large scale and most comprehensive study to date on this
association, suggest that higher levels of leisure-time physical activity may
lower risk of CP/CPPS in middle-age and older men.
PMID- 25116089
TI - [Shaping demographic change].
PMID- 25116088
TI - [Paralytic ileus after ileocystoplasty in a patient with spinal cord injury: is
homeopathy helpful?].
AB - A paralytic ileus is a typical complication of ileocystoplasty of the bladder. In
patients with a spinal cord injury, this risk is higher due to a preexisting
neurogenic bowel dysfunction. We present the case of a paraplegic man who
developed a massive paralytic ileus after ileocystoplasty and surgical revision.
Conventional stimulation of bowel function was unsuccessful; only by an
adjunctive homeopathic treatment was normalization of bowel function achieved.
Adjunctive homeopathic therapy is a promising treatment option in patients with
complex bowel dysfunction after abdominal surgery who do not adequately respond
to conventional treatment.
PMID- 25116090
TI - The phosphoproteome of Aspergillus nidulans reveals functional association with
cellular processes involved in morphology and secretion.
AB - We describe the first phosphoproteome of the model filamentous fungus Aspergillus
nidulans. Phosphopeptides were enriched using titanium dioxide, separated using a
convenient ultra-long reverse phase gradient, and identified using a "high-high"
strategy (high mass accuracy on the parent and fragment ions) with higher-energy
collisional dissociation. Using this approach 1801 phosphosites, from 1637 unique
phosphopeptides, were identified. Functional classification revealed
phosphoproteins were overrepresented under GO categories related to fungal
morphogenesis: "sites of polar growth," "vesicle mediated transport," and
"cytoskeleton organization." In these same GO categories, kinase-substrate
analysis of phosphoproteins revealed the majority were target substrates of CDK
and CK2 kinase families, indicating these kinase families play a prominent role
in fungal morphogenesis. Kinase-substrate analysis also identified 57 substrates
for kinases known to regulate secretion of hydrolytic enzymes (e.g. PkaA, SchA,
and An-Snf1). Altogether this data will serve as a benchmark that can be used to
elucidate regulatory networks functionally associated with fungal morphogenesis
and secretion. All MS data have been deposited in the ProteomeXchange with
identifier PXD000715
(http://proteomecentral.proteomexchange.org/dataset/PXD000715).
PMID- 25116091
TI - Halogen-free bis(imidazolium)/bis(ammonium)-di[bis(salicylato)borate] ionic
liquids as energy-efficient and environmentally friendly lubricant additives.
AB - Bis(imidazolium)- and bis(ammonium)-di[bis(salicylato)borate] ionic liquids with
variable alkyl chain and cyclic ring structures, were synthesized and then
evaluated them as potential lubricant additives. The copper strip test results
revealed noncorrosive properties of these ionic liquids. Introduction of halogen
content in bis(imidazolium) ionic liquid by replacement of bis(salicylato)borate
(BScB) anion with hexafluorophosphate (PF6(-)), severely corroded the copper
strip. Thermogravimetric results showed that bis(imidazolium) ionic liquids
exhibited higher thermal stability than bis(ammonium) ionic liquids owing to
compact structure provided by imidazolium rings, higher intermolecular
interactions, smaller free volume and low steric hindrance. The lubrication
properties of these ionic liquids as additives to synthetic lubricant
poly(ethylene) glycol (PEG 200) were evaluated for steel balls. Results showed
that bis(ammonium)- and bis(imidazolium)-(BScB)2 ionic liquids as additives
significantly reduced both friction coefficient and wear of PEG 200. The
structure of cations, particularly the variation in substituted alkyl chain
length monitored the degree of reduction in friction and wear. The excellent
lubrication properties were attributed to the formation of adsorbed tribo-thin
film and tribochemical product during the tribo-contact. Being halogen-,
phosphorus-, and sulfur-free, these ionic liquids (a) protects contact surfaces
from tribo-corrosive events, (b) reduces the friction and wear, and (c) keep
environment green and clean.
PMID- 25116092
TI - Changing concepts of diagnostic criteria of myeloproliferative disorders and the
molecular etiology and classification of myeloproliferative neoplasms: from
Dameshek 1950 to Vainchenker 2005 and beyond.
AB - The Polycythemia Vera Study Group (PVSG) and WHO classifications distinguished
the Philadelphia (Ph(1)) chromosome-positive chronic myeloid leukemia from the
Ph(1)-negative myeloproliferative neoplasms (MPN) essential thrombocythemia (ET),
polycythemia vera (PV) and primary myelofibrosis (MF) or primary megakaryocytic
granulocytic myeloproliferation (PMGM). Half of PVSG/WHO-defined ET patients show
low serum erythropoietin levels and carry the JAK2(V617F) mutation, indicating
prodromal PV. The positive predictive value of a JAK2(V617F) PCR test is 95% for
the diagnosis of PV, and about 50% for ET and MF. The WHO-defined JAK2(V617F)
positive ET comprises three ET phenotypes at clinical and bone marrow level when
the integrated WHO and European Clinical, Molecular and Pathological (ECMP)
criteria are applied: normocellular ET (WHO-ET), hypercellular ET due to
increased erythropoiesis (prodromal PV) and hypercellular ET associated with
megakaryocytic granulocytic myeloproliferation (EMGM). Four main molecular types
of clonal MPN can be distinguished: JAK2(V617F)-positive ET and PV; JAK2 wild
type ET carrying the MPL(515); mutations in the calreticulin (CALR) gene in
JAK2/MPL wild-type ET and MF, and a small proportion of JAK2/MPL/CALR wild-type
ET and MF patients. The JAK2(V617F) mutation load is low in heterozygous
normocellular WHO-ET. The JAK2(V617F) mutation load in hetero-/homozygous PV and
EMGM is clearly related to MPN disease burden in terms of splenomegaly,
constitutional symptoms and fibrosis. The JAK2 wild-type ET carrying the MPL(515)
mutation is featured by clustered small and giant megakaryocytes with
hyperlobulated stag-horn-like nuclei, in a normocellular bone marrow (WHO-ET),
and lacks features of PV. JAK2/MPL wild-type, CALR mutated hypercellular ET
associated with PMGM is featured by dense clustered large immature dysmorphic
megakaryocytes and bulky (cloud-like) hyperchromatic nuclei, which are never seen
in WHO-ECMP-defined JAK2(V617F) mutated ET, EMGM and PV, and neither in JAK2 wild
type ET carrying the MPL(515) mutation. Two thirds of JAK2/MPL wild-type ET and
MF patients carry one of the CALR mutations as the cause of the third distinct
MPN entity. WHO-ECMP criteria are recommended to diagnose, classify and stage the
broad spectrum of MPN of various molecular etiologies.
PMID- 25116093
TI - The old but new IgM Fc receptor (FcMUR).
AB - IgM is the first Ig isotype to appear during phylogeny, ontogeny and the immune
response. The importance of both pre-immune "natural" and antigen-induced
"immune" IgM antibodies in immune responses to pathogens and self-antigens has
been established by studies of mutant mice deficient in IgM secretion. Effector
proteins interacting with the Fc portion of IgM, such as complement and
complement receptors, have thus far been proposed, but fail to fully account for
the IgM-mediated immune protection and regulation of immune responses.
Particularly, the role of the Fc receptor for IgM (FcMUR) in such effector
functions has not been explored until recently. We have identified an authentic
FcMUR in humans using a functional cloning strategy and subsequently in mice by
RT-PCR and describe here its salient features and the immunological consequences
of FcMUR deficiency in mice. Since the FcMUR we cloned was identical to Toso or
Fas inhibitory molecule 3 (FAIM3), there have been spirited debates regarding the
real function of FcMUR/Toso/FAIM3 and we will also comment on this topic.
PMID- 25116095
TI - Intracellular antibody immunity and the cytosolic Fc receptor TRIM21.
AB - Until recently, it was thought that antibody effector mechanisms were mediated
purely by Fc receptors expressed on professional cells, following capture of
immune complexes in the extracellular space. Recently a new Fc receptor, TRIM21,
was discovered that is expressed by cells of all histogenetic lineages and which
mediates immune responses intracellularly. This new receptor possesses many
unique structural and functional properties. TRIM21 binds both IgG and IgM,
interacts primarily with the CH3 rather than CH2 domain and engages two heavy
chains simultaneously. This latter property allows TRIM21 to bind antibodies with
a higher affinity than any other Fc receptor. TRIM21 is cytosolic, has both
effector and signalling functions and is exquisitely conserved in mammals. The
discovery of this missing part of humoral immunity has important implications for
where and how antibodies work.
PMID- 25116096
TI - Computational modeling of the main signaling pathways involved in mast cell
activation.
AB - A global and rigorous understanding of the signaling pathways and cross
regulatory processes involved in mast cell activation requires the integration of
published information with novel functional datasets into a comprehensive
computational model. Based on an exhaustive curation of the existing literature
and using the software CellDesigner, we have built and annotated a comprehensive
molecular map for the FcepsilonRI signaling network. This map can be used to
visualize and interpret high-throughput expression data. Furthermore, leaning on
this map and using the logical modeling software GINsim, we have derived a
qualitative dynamical model, which recapitulates the most salient features of
mast cell activation. The resulting logical model can be used to explore the
dynamical properties of the system and its responses to different stimuli, in
normal or mutant conditions.
PMID- 25116097
TI - Calcium channels in Fc receptor signaling.
AB - The calcium ion (Ca(2+)) is the main common second messenger involved in
signaling transduction subsequent to immunoreceptor activation. Its rapid
intracellular elevation induces multiple cellular responses, such as secretion,
proliferation, mobility, and gene transcription. Intracellular levels of Ca(2+)
need to reach a specific threshold to efficiently transduce the signal to
activate transcription factors through the recruitment of Ca(2+)-binding
molecules. However, since Ca(2+) cannot be metabolized, its intracellular
concentration is tightly regulated to avoid the induction of programmed cell
death. This highly controlled regulation of Ca(2+) homeostasis has recently been
clarified by the uncovering of new ion channels. The regulation of these channels
allows the role of Ca(2+) in Fc receptor transduction pathways to be more
precisely defined.
PMID- 25116094
TI - Emerging roles for the FCRL family members in lymphocyte biology and disease.
AB - Members of the extended Fc receptor-like (FCRL) family in humans and mice are
preferentially expressed by B cells and possess tyrosine-based immunoregulatory
function. Although the majority of these proteins repress B cell receptor
mediated activation, there is an emerging evidence for their bifunctionality and
capacity to counter-regulate adaptive and innate signaling pathways. In light of
these findings, the recent discovery of ligands for several of these molecules
has begun to reveal exciting potential for them in normal lymphocyte biology and
is launching a new phase of FCRL investigation. Importantly, these fundamental
developments are also setting the stage for defining their altered roles in the
pathogenesis of a growing number of immune-mediated diseases. Here we review
recent advances in the FCRL field and highlight the significance of these
intriguing receptors in normal and perturbed immunobiology.
PMID- 25116098
TI - Regulation of FcepsilonRI signaling by lipid phosphatases.
AB - Mast cells (MCs) are tissue-resident sentinels of hematopoietic origin that play
a prominent role in allergic diseases. They express the high-affinity receptor
for IgE (FcepsilonRI), which when cross-linked by multivalent antigens triggers
the release of preformed mediators, generation of arachidonic acid metabolites,
and the synthesis of cytokines and chemokines. Stimulation of the FcepsilonRI
with increasing antigen concentrations follows a characteristic bell-shaped dose
responses curve. At high antigen concentrations, the so-called supra-optimal
conditions, repression of FcepsilonRI-induced responses is facilitated by
activation and incorporation of negative signaling regulators. In this context,
the SH2-containing inositol-5'-phosphatase, SHIP1, has been demonstrated to be of
particular importance. SHIP1 with its catalytic and multiple protein interaction
sites provides several layers of control for FcepsilonRI signaling. Regulation of
SHIP1 function occurs on various levels, e.g., protein expression, receptor and
membrane recruitment, competition for protein-protein interaction sites, and
activating modifications enhancing the phosphatase function. Apart from
FcepsilonRI-mediated signaling, SHIP1 can be activated by diverse unrelated
receptor systems indicating its involvement in the regulation of antigen
dependent cellular responses by autocrine feedback mechanisms or tissue-specific
and/or (patho-) physiologically determined factors. Thus, pharmacologic
engagement of SHIP1 may represent a beneficial strategy for patients suffering
from acute or chronic inflammation or allergies.
PMID- 25116099
TI - Fc receptors as adaptive immunoreceptors.
AB - Most biological activities of antibodies depend on their ability to engage
Receptors for the Fc portion of immunoglobulins (FcRs) on a variety of cell
types. As FcRs can trigger positive and negative signals, as these signals
control several biological activities in individual cells, as FcRs are expressed
by many cells of hematopoietic origin, mostly of the myeloid lineage, as these
cells express various combinations of FcRs, and as FcR-expressing cells have
different functional repertoires, antibodies can exert a wide spectrum of
biological activities. Like B and T Cell Receptors (BCRs and TCRs), FcRs are bona
fide immunoreceptors. Unlike BCRs and TCRs, however, FcRs are immunoreceptors
with an adaptive specificity for antigen, with an adaptive affinity for
antibodies, with an adaptive structure and with an adaptive signaling. They
induce adaptive biological responses that depend on their tissue distribution and
on FcR-expressing cells that are selected locally by antibodies. They critically
determine health and disease. They are thus exquisitely adaptive therapeutic
tools.
PMID- 25116100
TI - Glycosylation and Fc receptors.
AB - Immunoglobulins and Fc receptors are critical glycoprotein components of the
immune system. Fc receptors bind the Fc (effector) region of antibody molecules
and communicate information within the innate and adaptive immune systems.
Glycosylation of antibodies, particularly in the Fc region of IgG, has been
extensively studied in health and disease. The N-glycans in the identical heavy
chains have been shown to be critical for maintaining structural integrity,
communication with the Fc receptor and the downstream immunological response.
Less is known about glycosylation of the Fc receptor in either healthy or disease
states, however, recent studies have implicated an active role for receptor
associated oligosaccharides in the antibody-receptor interaction. Research into
Fc receptor glycosylation is increasing rapidly, where Fc receptors are routinely
used to analyze the binding of therapeutic monoclonal antibodies and where
glycosylation of receptors expressed by cells of the immune system could
potentially be used to mediate and control the differential binding of
immunoglobulins. Here we discuss the glycosylation of immunoglobulin antibodies
(IgA, IgE, IgG) and the Fc receptors (FcalphaR, FcepsilonR, FcgammaR, FcRn) that
bind them, the function of carbohydrates in the immune response and recent
advances in our understanding of these critical glycoproteins.
PMID- 25116101
TI - Antibodies as natural adjuvants.
AB - Antibodies in complex with specific antigen can dramatically change the antibody
response to this antigen. Depending on antibody class and type of antigen, >99 %
suppression or >100-fold enhancement of the response can take place. IgM and IgG3
are efficient enhancers and operate via the complement system. In contrast, IgG1,
IgG2a, and IgG2b enhance antibody and CD4(+) T cell responses to protein antigens
via activating Fcgamma-receptors. IgE also enhances antibody and CD4(+) T cell
responses to small proteins but uses the low-affinity receptor for IgE, CD23.
Most likely, IgM and IgG3 work by increasing the effective concentration of
antigen on follicular dendritic cells in splenic follicles. IgG1, IgG2a, IgG2b,
and IgE probably enhance antibody responses by increasing antigen presentation by
dendritic cells to T helper cells. IgG antibodies of all subclasses have a dual
effect, and suppress antibody responses to particulate antigens such as
erythrocytes. This capacity is used in the clinic to prevent immunization of
Rhesus-negative women to Rhesus-positive fetal erythrocytes acquired via
transplacental hemorrage. IgG-mediated suppression in mouse models can take place
in the absence of Fcgamma-receptors and complement and to date no knock-out mouse
strain has been found where suppression is abrogated.
PMID- 25116102
TI - IgA, IgA receptors, and their anti-inflammatory properties.
AB - Immunoglobulin A (IgA) is the most abundantly produced antibody isotype in
mammals. The primary function of IgA is to maintain homeostasis at mucosal
surfaces and play a role in immune protection. IgA functions mainly through
interaction with multiple receptors including IgA Fc receptor I (FcalphaRI),
transferrin receptor 1 (CD71), asialoglycoprotein receptor (ASGPR), Fcalpha/MUR,
FcRL4, and DC-SIGN/SIGNR1. In this review we discuss recent data demonstrating
anti-inflammatory functions of IgA through two receptors, the FcalphaRI and DC
SIGN/SIGNR1 interactions in the regulation of immunity. Serum monomeric IgA is
able to mediate an inhibitory signal following the interaction with FcalphaRI. It
results in partial phosphorylation of its FcRgamma-ITAM and the recruitment of
the tyrosine phosphatase SHP-1, which induces cell inhibition following the
formation of intracellular clusters named inhibisomes. In contrast, cross-linking
of FcalphaRI by multimeric ligands induces a full phosphorylation of the FcRgamma
ITAM leading to the recruitment of the tyrosine kinase Syk and cell activation.
In addition, secretory IgA can mediate a potent anti-inflammatory function
following the sugar-dependent interaction with SIGNR1 on dendritic cells which
induces an immune tolerance via regulatory T cell expansion. Overall, the anti
inflammatory effect of serum and secretory IgA plays a crucial role in the
physiology and in the prevention of tissue damage in multiple autoimmune and
inflammatory diseases.
PMID- 25116103
TI - humanized mice to study FcgammaR function.
AB - Passive immunotherapy represents a promising therapeutic intervention for a
number of neoplastic, chronic inflammatory, and infectious diseases, with several
monoclonal antibodies currently under development or already in use in the
clinic. While Fab-antigen interactions play a crucial role in the activity of an
antibody, it has become clear that Fc-mediated effector functions are involved
during antibody-mediated activities in vivo. A complete understanding of the
contributions of effector activities mediated by an antibody during its in vivo
function is required for the development of antibodies with improved therapeutic
efficacies. Animal models that are commonly used for the preclinical evaluation
of antibodies include murine and non-human primate species, whose FcgammaRs
present substantial structural, functional, and genetic variation compared with
their human counterparts. Therefore, the use of such animal models provides
limited information on the role of human IgG Fc-FcgammaR interactions during the
in vivo activities of antibodies intended for human therapeutics. In this
chapter, we describe the development and evaluation of an FcgammaR-humanized
mouse model for the study of human FcgammaR function in vivo. In this model,
endogenous mouse FcgammaR genes have been deleted and human FcgammaRs are
expressed as transgenes that faithfully recapitulate the unique pattern of human
FcgammaR expression. Evaluation of the in vivo activities of a number of
cytotoxic or therapeutic antibodies using FcgammaR-humanized mice provided useful
insights into human IgG Fc effector function. This mouse model has become a vital
preclinical model for testing therapeutic human antibodies to treat malignancies,
autoimmunity, inflammation, and infectious disease.
PMID- 25116104
TI - FcRn: from molecular interactions to regulation of IgG pharmacokinetics and
functions.
AB - The neonatal Fc receptor, FcRn, is related to MHC class I with respect to its
structure and association with beta2microglobulin (beta2m). However, by contrast
with MHC class I molecules, FcRn does not bind to peptides, but interacts with
the Fc portion of IgGs and belongs to the Fc receptor family. Unlike the
'classical' Fc receptors, however, the primary functions of FcRn include salvage
of IgG (and albumin) from lysosomal degradation through the recycling and
transcytosis of IgG within cells. The characteristic feature of FcRn is pH
dependent binding to IgG, with relatively strong binding at acidic pH (<6.5) and
negligible binding at physiological pH (7.3-7.4). FcRn is expressed in many
different cell types, and endothelial and hematopoietic cells are the dominant
cell types involved in IgG homeostasis in vivo. FcRn also delivers IgG across
cellular barriers to sites of pathogen encounter and consequently plays a role in
protection against infections, in addition to regulating renal filtration and
immune complex-mediated antigen presentation. Further, FcRn has been targeted to
develop both IgGs with extended half-lives and FcRn inhibitors that can lower
endogenous antibody levels. These approaches have implications for the
development of longer lived therapeutics and the removal of pathogenic or
deleterious antibodies.
PMID- 25116106
TI - Bridging autoantibodies and arthritis: the role of Fc receptors.
AB - Autoantibodies represent a hallmark of Rheumatoid arthritis (RA), which is a
chronic inflammatory autoimmune disease characterized by inflammation and damage
in the joints. Anti-Citrullinated Protein Antibodies (ACPA) are the most
prominent autoantibodies present in RA patients. These autoantibodies have been
intensively investigated during the last 20 years due to their diagnostic and
predictive value. Furthermore, they are believed to be involved in mediating the
damage associated with RA. Antibodies of the IgG isotype interact with the immune
system via Fcgamma receptors expressed on immune cells as well as nonimmune
cells. These receptors, therefore, form the bridge between Fcgamma receptor
positive cells and antibodies complexed to antigen allowing the modulation and
activation of cellular immune responses that are involved in immune defense
against invading microorganisms. However, in case triggered by antibodies against
self-antigens, they can also play a pivotal role in the induction and
perpetuation of autoimmune diseases such as RA. Mouse models have been
indispensably important for understanding the role of Fcgamma receptors in the
development of arthritis. Here we discuss the contribution of autoantibodies to
the pathogenesis of arthritis in preclinical animal models, as well as RA, in
relation to their interaction with the different (immune inhibitory and
activating) Fcgamma receptors.
PMID- 25116107
TI - The FcgammaR of humans and non-human primates and their interaction with IgG:
implications for induction of inflammation, resistance to infection and the use
of therapeutic monoclonal antibodies.
AB - Considerable effort has focused on the roles of the individual members of the
FcgammaR receptor (FcgammaR) family in inflammatory diseases and humoral
immunity. Recent work has revealed major roles in infection and in particular HIV
pathogenesis and immunity. In addition, FcgammaR functions underpin the action of
many of the successful therapeutic monoclonal antibodies. This emphasises the
need for a greater understanding of FcgammaR function in humans and in the NHP
which provides a key model for human immunity and preclinical testing of
antibodies. We discuss recent key aspects of the human FcgammaR receptor biology
and structure to define differences and similarities in activity between the
human and macaque Fc receptors. These differences and similarities nuance the
interpretation of infection and vaccine studies in the macaque. Indeed passive
IgG antibody protection in lentivirus infection models in the macaque provided
early evidence for the role of Fc receptors in anti-HIV immunity that have
subsequently gained support from human vaccine trials. None-the-less the diverse
functions and cellular contexts of FcgammaR receptor expression ensure there is
much still to understand of the protective and deleterious effects of FcgammaRs
in HIV infection. Careful comparative studies of human and non-human primate
FcgammaRs will facilitate our appreciation of what attributes of HIV specific IgG
antibodies, either acquired naturally or via vaccination, are most important for
protection.
PMID- 25116108
TI - FcgammaRIIB as a key determinant of agonistic antibody efficacy.
AB - Fc gamma Receptor (FcgammaR) IIB (CD32B) is an immunoreceptor tyrosine inhibitory
motif (ITIM)-bearing Fc receptor that is involved in abrogating the signalling
and function delivered from other receptors; archetypally those arising from
other, activatory, FcgammaR and from the B cell receptor (BCR) for antigen. In
the context of immunotherapy, it has convincingly been shown to limit a variety
of clinically important therapeutic monoclonal antibodies (mAb) such as rituximab
and trastuzumab in preclinical models. However, recent exploration of so-called
immunomodulatory mAb, for example agonist mAb directed against various members of
the TNFR super-family, has cast new light on the ability of FcgammaRIIB to
regulate immune responses and immunotherapy. These data, accumulated by several
independent groups, have shown the seemingly paradoxical ability of FcgammaRIIB
to augment or even be absolutely required for the activity of this class of mAb.
In this review we highlight the key role of FcgammaRIIB in regulating agonistic
mAb, detail the likely mechanism of action and propose new ways in which this
information may be exploited therapeutically.
PMID- 25116109
TI - Fc receptor-dependent mechanisms of monoclonal antibody therapy of cancer.
AB - Targeted therapies like treatment with monoclonal antibodies (mAbs) have entered
the arsenal of modern anticancer drugs. mAbs combine specificity with multiple
effector functions that can lead to reduction of tumour burden. Direct mechanisms
of action, including induction of apoptosis or growth inhibition, depend on the
biology of the target antigen. Fc tails of mAbs have furthermore the potential to
initiate complement-dependent lysis as well as immune effector cell-mediated
tumour cell killing via binding to Fc receptors. Natural killer cells can induce
apoptosis via antibody-dependent cellular cytotoxicity (ADCC), whereas
macrophages are able to phagocytose mAb-opsonized tumour cells (antibody
dependent cellular phagocytosis; ADCP). Finally, neutrophils can induce non
apoptotic tumour cell death, especially in the presence of immunoglobulin A (IgA)
antitumour mAbs. In spite of promising clinical successes in some malignancies,
improvement of mAb immunotherapy is required to achieve overall complete
remission in cancer patients. New strategies to enhance Fc receptor-mediated
mechanisms of action or to overcome the immunosuppressive microenvironment of the
tumour in mAb therapy of cancer are therefore currently being explored and will
be addressed in this chapter.
PMID- 25116110
TI - Sweet and sour: the role of glycosylation for the anti-inflammatory activity of
immunoglobulin G.
AB - The importance of immunoglobulin G (IgG) molecules for providing long-term
sterile immunity as well as their major contribution to tissue inflammation
during autoimmune diseases is generally accepted. In a similar manner, studies
over the last years have elucidated many details of the molecular and cellular
pathways underlying this protective activity in vivo, emphasizing the role of
cellular recognizing the constant antibody fragment. In contrast, the active anti
inflammatory activity of IgG, despite being known and actually identified in
human autoimmune patients more than 30 years ago, is much less defined. Recent
evidence from several independent model systems suggests that IgG glycosylation
is critical for the immunomodulatory activity of IgG and that both monomeric IgG
as well as IgG immune complexes can diminish Fc receptor and complement dependent
inflammatory processes. Moreover, there is increasing evidence that IgG molecules
also modulate B and T cell responses, which may suggest that IgG is centrally
involved in the establishment and maintenance of immune homeostasis.
PMID- 25116111
TI - High aspect ratio nano-fabrication of photonic crystal structures on glass wafers
using chrome as hard mask.
AB - Wafer-scale nano-fabrication of silicon nitride (Si x N y ) photonic crystal
(PhC) structures on glass (quartz) substrates is demonstrated using a thin (30
nm) chromium (Cr) layer as the hard mask for transferring the electron beam
lithography (EBL) defined resist patterns. The use of the thin Cr layer not only
solves the charging effect during the EBL on the insulating substrate, but also
facilitates high aspect ratio PhCs by acting as a hard mask while deep etching
into the Si x N y . A very high aspect ratio of 10:1 on a 60 nm wide grating
structure has been achieved while preserving the quality of the flat top of the
narrow lines. The presented nano-fabrication method provides PhC structures
necessary for a high quality optical response. Finally, we fabricated a
refractive index based PhC sensor which shows a sensitivity of 185 nm per RIU.
PMID- 25116105
TI - Human FcR polymorphism and disease.
AB - Fc receptors play a central role in maintaining the homeostatic balance in the
immune system. Our knowledge of the structure and function of these receptors and
their naturally occurring polymorphisms, including single nucleotide
polymorphisms and/or copy number variations, continues to expand. Through studies
of their impact on human biology and clinical phenotype, the contributions of
these variants to the pathogenesis, progression, and/or treatment outcome of many
diseases that involve immunoglobulin have become evident. They affect
susceptibility to bacterial and viral pathogens, constitute as risk factors for
IgG or IgE mediated inflammatory diseases, and impact the development of many
autoimmune conditions. In this chapter, we will provide an overview of these
genetic variations in classical FcgammaRs, FcRLs, and other Fc receptors, as well
as challenges in achieving an accurate and comprehensive understanding of the FcR
polymorphisms and genomic architecture.
PMID- 25116116
TI - Effects of foot placement, hand positioning, age and climbing biodynamics on
ladder slip outcomes.
AB - Ladder falls frequently cause severe injuries; yet the factors that influence
ladder slips/falls are not well understood. This study aimed to quantify (1) the
effects of restricted foot placement, hand positioning, climbing direction and
age on slip outcomes, and (2) differences in climbing styles leading to slips
versus styles leading to non-slips. Thirty-two occupational ladder users from
three age groups (18-24, 25-44 and 45-64 years) were unexpectedly slipped
climbing a vertical ladder, while being assigned to different foot placement
conditions (unrestricted vs. restricted toe clearance) and different hand
positions (rails vs. rungs). Constraining foot placement increased the climber's
likelihood of slipping (p < 0.01), while younger and older participants slipped
more than the middle-aged group (p < 0.01). Longer double stance time, dissimilar
and more variable foot and body positioning were found in styles leading to a
slip. Maintaining sufficient toe clearance and targeting ladder safety training
to younger and older workers may reduce ladder falls. Practitioner Summary:
Ladder falls frequently cause severe occupational fall injuries. This study aims
to identify safer ladder climbing techniques and individuals at risk of falling.
The results suggest that ladders with unrestricted toe clearance and ladder
climbing training programmes, particularly for younger and older workers, may
reduce ladder slipping risk.
PMID- 25116117
TI - Erythroidine alkaloids: a novel class of phytoestrogens.
AB - Erythrina poeppigiana is a medicinal plant which is widely used in Asia, Latin
America, and Africa in traditional remedies for gynecological complications and
maladies. In continuation of studies for the discovery of novel phytoestrogens,
four erythroidine alkaloids, namely alpha-erythroidine, beta-erythroidine, and
their oxo-derivatives 8-oxo-alpha-erythroidine and 8-oxo-beta-erythroidine, were
isolated and structurally characterized from the methanolic extract of the stem
bark of E. poeppigiana. Due to the high amounts of erythroidines in the extract
and considering the widespread utilization of Erythrina preparations in
traditional medicine, the exploration of their estrogenic properties was
performed. The estrogenicity of the isolated erythroidines was assayed in various
estrogen receptor-(ER)-dependent test systems, including receptor binding
affinity, cell culture based ER-dependent reporter gene assays, and gene
expression studies in cultured cells using reverse transcription polymerase chain
reaction techniques. alpha-Erythroidine and beta-erythroidine showed binding
affinity values for ERalpha of 0.015 +/- 0.010% and 0.005 +/- 0.010%,
respectively, whereas only beta-erythroidine bound to ERbeta (0.006 +/- 0.010%).
In reporter gene assays, both erythroidines exhibited a significant dose
dependent estrogenic stimulation of ER-dependent reporter gene activity in
osteosarcoma cells detectable already at 10 nM. Results were confirmed in the
MVLN cells, a bioluminescent variant of MCF-7 breast cancer cells. Further, alpha
erythroidine and beta-erythroidine both induced the enhanced expression of the
specific ERalpha-dependent genes trefoil factor-1 and serum/glucocorticoid
regulated kinase 3 in MCF-7 cells, confirming estrogenicity. Additionally, using
molecular docking simulations, a potential mode of binding on ERalpha, is
proposed, supporting the experimental evidences. This is the first time that an
estrogenic profile is reported for erythroidine alkaloids, potentially a new
class of phytoestrogens.
PMID- 25116118
TI - Ruscogenin protects against high-fat diet-induced nonalcoholic steatohepatitis in
hamsters.
AB - The protective effects of ruscogenin on nonalcoholic steatohepatitis in hamsters
fed a high-fat diet were investigated. Ruscogenin (0.3, 1.0, or 3.0 mg/kg/day)
was orally administered by gavage once daily for eight weeks. A high-fat diet
induced increases in plasma levels of total cholesterol, triglycerides, and free
fatty acids, while the degree of insulin resistance was lowered by ruscogenin.
High-fat diet-induced hepatic steatosis and necroinflammation were improved by
ruscogenin. Gene expression of inflammatory cytokines and activity of nuclear
transcription factor-kappaB were also increased in the high-fat diet group, which
were attenuted by ruscogenin. Ruscogenin decreased hepatic mRNA levels of sterol
regulatory element-binding protein-1c and its lipogenic target genes. The hepatic
mRNA expression of peroxisome proliferator-activated receptor alpha, together
with its target genes responsible for fatty acid beta-oxidation were upregulated
by ruscogenin. In conclusion, these findings suggest that ruscogenin may
attenuate high-fat diet-induced steatohepatitis through anti-inflammatory
mechanisms, reducing hepatic lipogenic gene expression, and upregulating proteins
in the fatty acid oxidation process.
PMID- 25116119
TI - Transport in Caco-2 cell monolayers of antidiabetic cucurbitane triterpenoids
from Momordica charantia fruits.
AB - Bitter melon, the fruit of Momordica charantia L. (Cucurbitaceae), is a widely
used treatment for diabetes in traditional medicine systems throughout the world.
Various compounds have been shown to be responsible for this reputed activity,
and, in particular, cucurbitane triterpenoids are thought to play a significant
role. The objective of this study was to investigate the gastrointestinal
transport of a triterpenoid-enriched n-butanol extract of M. charantia using a
two-compartment transwell human intestinal epithelial cell Caco-2 monolayer
system, simulating the intestinal barrier. Eleven triterpenoids in this extract
were transported from the apical to basolateral direction across Caco-2 cell
monolayers, and were identified or tentatively identified by HPLC-TOF-MS.
Cucurbitane triterpenoids permeated to the basolateral side with apparent
permeability coefficient (P app) values for 3-beta-7-beta,25-trihydroxycucurbita
5,23(E)-dien-19-al and momordicines I and II at 9.02 * 10(-6), 8.12 * 10(-6), and
1.68 * 10(-6)cm/s, respectively. Also, small amounts of these triterpenoids were
absorbed inside the Caco-2 cells. This is the first report of the transport of
the reputed antidiabetic cucurbitane triterpenoids in human intestinal epithelial
cell monolayers. Our findings, therefore, further support the hypothesis that
cucurbitane triterpenoids from bitter melon may explain, at least in part, the
antidiabetic activity of this plant in vivo.
PMID- 25116120
TI - Vermistatin derivatives with alpha-glucosidase inhibitory activity from the
mangrove endophytic fungus Penicillium sp. HN29-3B1.
AB - Three new vermistatin derivatives, 6-demethylpenisimplicissin (1), 5'
hydroxypenisimplicissin (2), and 2''-epihydroxydihydrovermistatin (3), along with
five known vermistatin analogues, methoxyvermistatin (4), vermistatin (5), 6
demethylvermistatin (6), hydroxyvermistatin (7), and penisimplicissin (8), were
isolated from the culture of the mangrove endophytic fungus Penicillium sp. HN29
3B1 from Cerbera manghas. Their structures were elucidated mainly by nuclear
magnetic resonance spectroscopy. The absolute configurations of compounds 1 and 2
were deduced on the basis of circular dichroism data. The absolute structures of
compounds 3 and 5 were confirmed by a single-crystal X-ray diffraction experiment
using Cu Kalpha radiation. In the bioactivity assay, compounds 1 and 3 exhibited
alpha-glucosidase inhibitory activity with IC50 values of 9.5 +/- 1.2 and 8.0 +/-
1.5 uM, respectively. The plausible biosynthetic pathways for all compounds are
discussed.
PMID- 25116121
TI - Extralevator abdominoperineal resection--a video vignette.
PMID- 25116122
TI - Hypoglycaemic role of wheatgrass and its effect on carbohydrate metabolic enzymes
in type II diabetic rats.
AB - Diabetes mellitus (DM) is a leading cause of morbidity and mortality in the
world. Insulin resistance and insulin insufficiency is the major factor for the
prognosis of type II diabetes. Consistent high glucose level leads to multiple
secondary complications in diabetic patients. Hence, hypoglycaemic drugs are of
significance for reducing the risk of secondary complications in type II
diabetes. Various hypoglycaemic drugs are already available in the market, but
they are associated with several side effects. Therefore, traditional herbs have
emerged as safer alternative for effective hypoglycaemic treatment. The juvenile
grass of common wheat is known as wheatgrass (WG). It is commonly used as a
health drink and has potent antioxidant efficacy. It has been used to cure DM in
folk medicine. The current study was planned to test the hypoglycaemic effect and
pathways regulated by WG on DM. We analysed the glucose and insulin levels in
plasma, the activity of glucose oxidative enzymes, hexokinase and glucose 6
phosphate dehydrogenase, in serum and glycogen levels in liver of the male albino
Wistar rats. Activity of glucose oxidative enzymes and the levels of insulin and
liver glycogen were decreased in rats with diabetes, but they were reversed on
treatment with WG. Hence, we conclude that WG can act as a potent anti
hyperglycaemic agent.
PMID- 25116123
TI - Catalytic formation of acrylate from carbon dioxide and ethene.
AB - With regard to sustainability, carbon dioxide (CO2) is an attractive C1 building
block. However, due to thermodynamic restrictions, reactions incorporating CO2
are relatively limited so far. One of the so-called "dream reactions" in this
field is the catalytic oxidative coupling of CO2 and ethene and subsequent beta-H
elimination to form acrylic acid. This reaction has been studied intensely for
decades. However up to this date no suitable catalytic process has been
established. Here we show that the catalytic conversion of ethene and CO2 to
acrylate is possible in the presence of a homogeneous nickel catalyst in
combination with a "hard" Lewis acid. For the first time, catalytic conversion of
CO2 and ethene to acrylate with turnover numbers (TON) of up to 21 was
demonstrated.
PMID- 25116126
TI - The use of plasma exchange in Hashimoto's encephalopathy: A case report and
review of the literature.
AB - Hashimoto's Encephalopathy (HE) is a very rare condition characterized by
psychosis, seizures, cognitive fluctuations, and myoclonus. In a few published
cases, plasma exchange has been used due to the theoretical removal of
antithyroid peroxidase antibodies (anti-TPO), one of the postulated causes of the
condition. We report a case of HE treated by plasma exchange where no clinical or
neurophysiologic improvement was observed despite documented reduction of the
anti-TPO antibody to levels below the limits of laboratory detection. We discuss
these findings in the context of the known literature for this disease process.
PMID- 25116125
TI - Celastrol inhibits lung infiltration in differential syndrome animal models by
reducing TNF-alpha and ICAM-1 levels while preserving differentiation in ATRA
induced acute promyelocytic leukemia cells.
AB - All-trans retinoic acid (ATRA) is a revolutionary agent for acute promyelocytic
leukemia (APL) treatment via differentiation induction. However, ATRA treatment
also increases cytokine, chemokine, and adhesive molecule (mainly ICAM-1)
expression, which can cause clinical complications, including a severe situation
known as differentiation syndrome (DS) which can cause death. Therefore, it is of
clinical significance to find a strategy to specifically blunt inflammatory
effects while preserving differentiation. Here we report that the natural
compound, celastrol, could effectively block lung infiltrations in DS animal
models created by loading ATRA-induced APL cell line NB4. In ATRA-treated NB4
cells, celastrol could potently inhibit ICAM-1 elevation and partially reduce TNF
alpha and IL-1beta secretion, though treatment showed no effects on IL-8 and MCP
1 levels. Celastrol's effect on ICAM-1 in ATRA-treated NB4 was related to
reducing MEK1/ERK1 activation. Strikingly and encouragingly, celastrol showed no
obvious effects on ATRA-induced NB4 differentiation, as determined by morphology,
enzymes, and surface markers. Our results show that celastrol is a promising and
unique agent for managing the side effects of ATRA application on APL, and
suggest that hyper-inflammatory ability is accompanied by, but not necessary for,
APL differentiation. Thus we offered an encouraging novel strategy to further
improve differentiation therapy.
PMID- 25116128
TI - Improved electrical performance and bias stability of solution-processed active
bilayer structure of indium zinc oxide based TFT.
AB - We fabricated active single- and bilayer structure thin film transistors (TFTs)
with aluminum or gallium doped (IZO:Al or IZO:Ga) and undoped indium zinc oxide
(IZO) thin film layers using an aqueous solution process. The electrical
performance and bias stability of these active single- and bilayer structure TFTs
were investigated and compared to reveal the effects of Al/Gal doping and bilayer
structure. The single-layer structure IZO TFT shows a high mobility of 19 cm(2)/V
. s with a poor positive bias stability (PBS) of DeltaVT + 3.4 V. However, Al/Ga
doped in IZO TFT reduced mobility to 8.5-9.9 cm(2)/V . s but improved PBS to
DeltaVT + 1.6-1.7 V due to the reduction of oxygen vacancy. Thus, it is found the
bilayer structure TFTs with a combination of bottom- and top-layer compositions
modify both the mobility and bias stability of the TFTs to be optimized. The
bilayer structure TFT with an IZO:X bottom layer possess high mobility and an IZO
bottom layer improves the PBS.
PMID- 25116127
TI - Second generation inactivated eastern equine encephalitis virus vaccine
candidates protect mice against a lethal aerosol challenge.
AB - Currently, there are no FDA-licensed vaccines or therapeutics for eastern equine
encephalitis virus (EEEV) for human use. We recently developed several methods to
inactivate CVEV1219, a chimeric live-attenuated eastern equine encephalitis virus
(EEEV). Dosage and schedule studies were conducted to evaluate the immunogenicity
and protective efficacy of three potential second-generation inactivated EEEV
(iEEEV) vaccine candidates in mice: formalin-inactivated CVEV1219 (fCVEV1219),
INA-inactivated CVEV1219 (iCVEV1219) and gamma-irradiated CVEV1219 (gCVEV1219).
Both fCVEV1219 and gCVEV1219 provided partial to complete protection against an
aerosol challenge when administered by different routes and schedules at various
doses, while iCVEV1219 was unable to provide substantial protection against an
aerosol challenge by any route, dose, or schedule tested. When evaluating
antibody responses, neutralizing antibody, not virus specific IgG or IgA, was the
best correlate of protection. The results of these studies suggest that both
fCVEV1219 and gCVEV1219 should be evaluated further and considered for
advancement as potential second-generation inactivated vaccine candidates for
EEEV.
PMID- 25116129
TI - Neurocognitive moderation of associations between cannabis use and
psychoneuroticism.
AB - BACKGROUND: Cannabis use has been associated with neurocognitive impairments and
psychopathology. The strength of such associations does however appear to depend
on many different factors, such as duration and intensity of use, but also
differential susceptibility due to genetic make-up and environmental influences.
The present study investigated whether specific cognitive weaknesses moderated
associations between cannabis use and psychoneuroticism, which may be considered
one of the "softer" expressions of an extended psychosis phenotype. METHOD: One
hundred and fifty (150) young adults (mean age: 24.7 years, SD: 3.7), mostly
college students, performed three computerized neuropsychological tasks: a
relatively easy social perception task (Face Recognition), a more complex social
perception task combining emotion recognition and executive functioning (Matching
Facial Emotions), and a more complex task requiring sustained attention and
executive functioning (Sustained Attention-Dots). Participants self-reported on
the extent to which they experienced psychological problems using the Symptom
Checklist-90 (SCL-90). The SCL-90 total score (psychoneuroticism) was used as
dependent variable in analyses of variance. RESULTS: Frequent and current
cannabis users performed more poorly than nonusers on the three tasks. They also
reported more psychoneuroticism than nonusers whether they were classified
according to their lifetime use, their use during the past 12 months, or use
during the past 4 weeks. Moderate and former users did not differ from nonusers.
Relatively poor performance on the Matching Facial Emotions task, as opposed to
performance on the Face Recognition and Sustained Attention tasks, augmented
levels of experienced psychoneuroticism among frequent and current cannabis
users. CONCLUSIONS: Relatively poor cognitive abilities appear to represent
increased vulnerability to effects of frequent and current cannabis use on
affective mental health, even among highly educated individuals. There seems to
be some specificity as to which (combinations of) neurocognitive abilities may be
most indicative, as moderating effects were only observed when participants had
relatively poor complex social perception ability.
PMID- 25116130
TI - Directed arene/alkyne annulation reactions via aerobic copper catalysis.
AB - We describe a straightforward protocol for a smooth dehydrogenative annulation
reaction between various arenes and terminal alkynes using a catalytic amount of
CuBr2 and molecular oxygen. 3-Methyleneisoindoline derivatives are prepared in
high yields.
PMID- 25116131
TI - The prognostic value of the hawkins sign and diagnostic value of MRI after talar
neck fractures.
AB - BACKGROUND: The early diagnosis of avascular necrosis of the talus (AVN) and
prediction of ankle function for talar fractures are important. The Hawkins sign,
as a radiographic predictor, could exclude the possibility of developing ischemic
bone necrosis after talar neck fractures, but its relationship with ankle
function remains unclear. The purpose of this study was to illustrate the
prognostic effect of the Hawkins sign on ankle function after talar neck
fractures and to study the value of early MRI in detecting the AVN changes after
talus fractures. METHODS: Cases of talar neck fractures between November 2008 and
November 2013 were evaluated. The occurrences of the Hawkins sign and AVN were
studied. X-ray imaging was performed at multiple time points from the 4th to the
12th week after the fractures, and MRI examinations were used in the Hawkins sign
negative group, with the time span ranging from 1.5 to 12 months. AOFAS scores of
the Hawkins sign positive and negative groups were compared during the follow-up.
Forty-four cases (48 feet) were evaluated. RESULTS: The occurrence of positive
Hawkins sign was 50%, 30%, and 33.3%, the incidence of AVN was 0%, 10%, and 50%,
respectively, in type I, type II, and type III and IV talus fractures,
respectively. The AOFAS scores showed no statistically significant difference
between Hawkins sign positive group and negative group in type I and II
fractures. The Hawkins sign positive group had better AOFAS scores than the
negative group in type III and IV fractures. However, there was no statistically
significant difference between Hawkins sign positive and negative groups when AVN
cases were excluded in type III and IV fractures. CONCLUSION: The Hawkins sign
was a reliable predictor excluding the possibility of AVN. It did not have
predictive value on the ankle function in low-energy fractures and may predict
better ankle function in high-energy fractures. MRI can diagnose AVN during an
earlier period, and we believe Hawkins sign negative patients should undergo MRI
examinations 12 weeks after the fractures, especially in high-energy traumatic
cases. LEVEL OF EVIDENCE: Level III, comparative case series.
PMID- 25116132
TI - Comparison of continuous nerve block versus patient-controlled analgesia for
postoperative pain and outcome after talar and calcaneal fractures.
AB - BACKGROUND: Talar and calcaneal fractures and their treatment can cause severe
postoperative pain. We hypothesized that a continuous peripheral nerve block
(CPNB) would reduce pain scores more effectively than systemic analgesics,
improve recovery, and lead to reduced length of stay (LOS). METHODS: Over a 3
year period patients undergoing open reduction and internal fixation (ORIF) of a
talar or calcaneal fracture were retrospectively analyzed. Patients received a
CPNB catheter preoperatively or intravenous patient-controlled analgesia (PCA)
postoperatively. Primary endpoint was Numerical Rating Scale (NRS) scores on
postoperative day 1. Secondary endpoints were NRS scores up to day 3, opioid
requirement, analgesia-related side effects, intraoperative blood loss,
infection, and LOS. Eighty-seven patients were analyzed; 70 with calcaneal
fracture, 21 with talar fracture, 4 with both. In all, 40 patients received CPNB,
47 patients PCA. RESULTS: Median NRS scores on day 1 were 1.0 (IQR 3) in the CPNB
group and 2.0 (IQR 3) in the PCA group (ns). Median LOS for patients with CPNB
was 5 days (IQR3) and PCA 4 days (IQR 2 ns). Blood loss and incidence of local
infections were comparable in both groups. Opioid requirement was significantly
increased in the PCA group (P < .01). CONCLUSION: Significant advantages or
disadvantages were not seen in either group. However, the PCA group required
about 30-fold more opioids compared to the CPNB group on day 1, although that did
not lead to an increased number of side effects. LEVEL OF EVIDENCE: Level III,
retrospective comparative series.
PMID- 25116133
TI - Changing aetiology of healthcare-associated bloodstream infections at three
medical centres in Taiwan, 2000-2011.
AB - This multicentre surveillance study was conducted to investigate the trends in
incidence and aetiology of healthcare-associated bloodstream infections (HCA
BSIs) in Taiwan. From 2000 to 2011 a total of 56 830 HCA-BSIs were recorded at
three medical centres, and coagulase-negative staphylococci (CoNS) were the most
common pathogens isolated (n = 9465, 16.7%), followed by E. coli (n = 7599,
13.4%). The incidence of all HCA-BSIs in each and all hospitals significantly
increased over the study period owing to the increase of aerobic Gram-positive
cocci and Enterobacteriaceae by 4.2% and 3.6%, respectively. Non-fermenting Gram
negative bacteria, Bacteroides spp. and Candida spp. also showed an increase but
there was a significant decline in the numbers of methicillin-resistant S.
aureus. In conclusion, the incidence of HCA-BSIs in Taiwan is significantly
increasing, especially for Enterobacteriaceae and aerobic Gram-positive cocci.
PMID- 25116134
TI - Spectrum of diseases diagnosed on bone marrow examination of 285 infants in a
single tertiary care center.
AB - OBJECTIVES: Bone marrow (BM) aspiration and trephine biopsy is one of the most
valuable procedures in the evaluation of hematological disorders. There is a
shortage of published literature regarding the indications, procedure, and
outcome of bone marrow examination (BME) in neonates and infants. The aim of the
present study is to analyze the common indications of performing BME and to
assess the spectrum of disorders diagnosed from BM of neonates and infants.
METHODS: A retrospective analysis of BMEs performed in infants over a period of 5
years, between 2009 and 2013 was done. RESULTS AND DISCUSSION: A total of 297 BME
were performed on 285 infants, which constitutes 10.3% of pediatric BME
procedures during the same period. In our institute, BME is routinely performed
by trained pathologists from posterior superior iliac spine in children including
infants and neonates with an overall sample adequacy of 97%. Evaluation of
cytopenias and suspicion of storage disorder were the most common indications for
BME procedure, while acute leukemias and storage disorders were the most common
diagnoses offered in infant BM. CONCLUSIONS: Posterior superior iliac spine is a
good site of BME in neonates and infants. BM trephine biopsy is a difficult
procedure in this age group, however remains indispensable in situations where an
infiltrative pathology is suspected. BME not only helps to make specific
diagnoses but should also be used as an extremely valuable, quick, and
economically viable procedure to exclude major hematological disorders including
certain forms of storage disorder and hematological malignancy in this age group.
PMID- 25116135
TI - Saccharomyces cerevisiae Sen1 as a model for the study of mutations in human
Senataxin that elicit cerebellar ataxia.
AB - The nuclear RNA and DNA helicase Sen1 is essential in the yeast Saccharomyces
cerevisiae and is required for efficient termination of RNA polymerase II
transcription of many short noncoding RNA genes. However, the mechanism of Sen1
function is not understood. We created a plasmid-based genetic system to study
yeast Sen1 in vivo. Using this system, we show that (1) the minimal essential
region of Sen1 corresponds to the helicase domain and one of two flanking nuclear
localization sequences; (2) a previously isolated terminator readthrough mutation
in the Sen1 helicase domain, E1597K, is rescued by a second mutation designed to
restore a salt bridge within the first RecA domain; and (3) the human ortholog of
yeast Sen1, Senataxin, cannot functionally replace Sen1 in yeast. Guided by
sequence homology between the conserved helicase domains of Sen1 and Senataxin,
we tested the effects of 13 missense mutations that cosegregate with the
inherited disorder ataxia with oculomotor apraxia type 2 on Sen1 function. Ten of
the disease mutations resulted in transcription readthrough of at least one of
three Sen1-dependent termination elements tested. Our genetic system will
facilitate the further investigation of structure-function relationships in yeast
Sen1 and its orthologs.
PMID- 25116136
TI - Genetic analysis of resistance and sensitivity to 2-deoxyglucose in Saccharomyces
cerevisiae.
AB - Aerobic glycolysis is a metabolic pathway utilized by human cancer cells and also
by yeast cells when they ferment glucose to ethanol. Both cancer cells and yeast
cells are inhibited by the presence of low concentrations of 2-deoxyglucose
(2DG). Genetic screens in yeast used resistance to 2-deoxyglucose to identify a
small set of genes that function in regulating glucose metabolism. A recent high
throughput screen for 2-deoxyglucose resistance identified a much larger set of
seemingly unrelated genes. Here, we demonstrate that these newly identified genes
do not in fact confer significant resistance to 2-deoxyglucose. Further, we show
that the relative toxicity of 2-deoxyglucose is carbon source dependent, as is
the resistance conferred by gene deletions. Snf1 kinase, the AMP-activated
protein kinase of yeast, is required for 2-deoxyglucose resistance in cells
growing on glucose. Mutations in the SNF1 gene that reduce kinase activity render
cells hypersensitive to 2-deoxyglucose, while an activating mutation in SNF1
confers 2-deoxyglucose resistance. Snf1 kinase activated by 2-deoxyglucose does
not phosphorylate the Mig1 protein, a known Snf1 substrate during glucose
limitation. Thus, different stimuli elicit distinct responses from the Snf1
kinase.
PMID- 25116138
TI - Adsorption of enzyme onto lignins of liquid hot water pretreated hardwoods.
AB - The adsorption of cellulase enzymes onto lignin is shown to be non-productive and
therefore reduces enzymatic hydrolysis of liquid hot water pretreated cellulose.
Among the enzyme components of Trichoderma reesei cellulase cocktail, beta
glucosidase showed the strongest adsorption onto lignin. Only 2-18% of the
initial beta-glucosidase activity remained in the supernatant while 50-60% of
cellobiohydrolase and endoglucanase activities were recovered after incubation
with lignin. By increasing the pH to 5.5 and adding NaCl to a 200 mM, the free
enzymes in the supernatant were increased but hydrolysis was not enhanced since
optimal pH for enzymatic hydrolysis is at 4.8. Electrostatic interactions
contributed to enzyme adsorption and their effect was most pronounced for T.
reesei beta-glucosidase which had high molecular weights (78-94 kDa) and high
isoelectric points (pI 5.7-6.4). Since the enzyme components which are required
to synergistically hydrolyze cellulose have different profiles (molecular weight,
hydrophobicity and pI), they exhibit different adsorption behaviors with lignin,
and thereby change the ratio of enzyme activities needed for synergism during
cellulose hydrolysis. beta-glucosidase from Aspergillus niger exhibits less
adsorption than beta-glucosidase from T. reesei. Supplemental addition of A.
niger beta-glucosidase to the enzyme mixture increases hydrolysis of pretreated
hardwood by a factor of two. The analysis presented in this paper shows that
lignins with higher guaiacyl content adsorb more cellulase enzymes, particularly
beta-glucosidase, and that adsorption of beta-glucosidase onto lignin indirectly
suppresses enzymatic hydrolysis of cellulose in pretreated hardwoods due to
decreased hydrolysis of cellobiose which in turn accumulates and inhibits CBH.
PMID- 25116137
TI - The conserved PFT1 tandem repeat is crucial for proper flowering in Arabidopsis
thaliana.
AB - It is widely appreciated that short tandem repeat (STR) variation underlies
substantial phenotypic variation in organisms. Some propose that the high
mutation rates of STRs in functional genomic regions facilitate evolutionary
adaptation. Despite their high mutation rate, some STRs show little to no
variation in populations. One such STR occurs in the Arabidopsis thaliana gene
PFT1 (MED25), where it encodes an interrupted polyglutamine tract. Although the
PFT1 STR is large (~270 bp), and thus expected to be extremely variable, it shows
only minuscule variation across A. thaliana strains. We hypothesized that the
PFT1 STR is under selective constraint, due to previously undescribed roles in
PFT1 function. We investigated this hypothesis using plants expressing transgenic
PFT1 constructs with either an endogenous STR or synthetic STRs of varying
length. Transgenic plants carrying the endogenous PFT1 STR generally performed
best in complementing a pft1 null mutant across adult PFT1-dependent traits. In
stark contrast, transgenic plants carrying a PFT1 transgene lacking the STR
phenocopied a pft1 loss-of-function mutant for flowering time phenotypes and were
generally hypomorphic for other traits, establishing the functional importance of
this domain. Transgenic plants carrying various synthetic constructs occupied the
phenotypic space between wild-type and pft1 loss-of-function mutants. By varying
PFT1 STR length, we discovered that PFT1 can act as either an activator or
repressor of flowering in a photoperiod-dependent manner. We conclude that the
PFT1 STR is constrained to its approximate wild-type length by its various
functional requirements. Our study implies that there is strong selection on STRs
not only to generate allelic diversity, but also to maintain certain lengths
pursuant to optimal molecular function.
PMID- 25116139
TI - Neural circuits: putting a stop to feeding.
PMID- 25116140
TI - Fly visual course control: behaviour, algorithms and circuits.
AB - Understanding how the brain controls behaviour is undisputedly one of the grand
goals of neuroscience research, and the pursuit of this goal has a long tradition
in insect neuroscience. However, appropriate techniques were lacking for a long
time. Recent advances in genetic and recording techniques now allow the
participation of identified neurons in the execution of specific behaviours to be
interrogated. By focusing on fly visual course control, I highlight what has been
learned about the neuronal circuit modules that control visual guidance in
Drosophila melanogaster through the use of these techniques.
PMID- 25116142
TI - Synaptic plasticity: a homeostatic messenger.
PMID- 25116143
TI - Chemically stable and mechanically durable superamphiphobic aluminum surface with
a micro/nanoscale binary structure.
AB - We developed a simple fabrication method to prepare a superamphiphobic aluminum
surface. On the basis of a low-energy surface and the combination of micro- and
nanoscale roughness, the resultant surface became super-repellent toward a wide
range of liquids with surface tensions of 25.3-72.1 mN m(-1). The applied
approach involved (1) the formation of an irregular microplateau structure on an
aluminum surface, (2) the fabrication of a nanoplatelet structure, and (3)
fluorination treatment. The chemical stability and mechanical durability of the
superamphiphobic surface were evaluated in detail. The results demonstrated that
the surface presented an excellent chemical stability toward cool corrosive
liquids (HCl/NaOH solutions, 25 degrees C) and 98% concentrated sulfuric acid,
hot liquids (water, HCl/NaOH solutions, 30-100 degrees C), solvent immersion,
high temperature, and a long-term period. More importantly, the surface also
exhibited robust mechanical durability and could withstand multiple-fold, finger
touch, intensive scratching by a sharp blade, ultrasonication treatment, boiling
treatment in water and coffee, repeated peeling by adhesive tape, and even
multiple abrasion tests under 500 g of force without losing superamphiphobicity.
The as-prepared superamphiphobic surface was also demonstrated to have excellent
corrosion resistance. This work provides a simple, cost-effective, and highly
efficient method to fabricate a chemically stable and mechanically robust
superamphiphobic aluminum surface, which can find important outdoor applications.
PMID- 25116141
TI - Localized GABAergic inhibition of dendritic Ca(2+) signalling.
AB - Neuronal circuits are defined by synaptic connections between their cellular
constituents. In this article, I highlight several recent studies emphasizing the
surprising level of precision exhibited by inhibitory GABAergic synapses within
the neocortex and hippocampus. Specifically, GABAergic inputs to dendritic shafts
and spines of pyramidal cells have a key role in the localized regulation of
neuronal Ca(2+) signalling. These findings provide important new insights into
the cellular mechanisms underlying the contributions of inhibitory transmission
to both normal and abnormal brain activity.
PMID- 25116144
TI - Metaproteomics: Evaluation of protein extraction from activated sludge.
AB - Metaproteomic studies of full-scale activated sludge systems require reproducible
protein extraction methods. A systematic evaluation of three different
extractions protocols, each in combination with three different methods of cell
lysis, and a commercial kit were evaluated. Criteria used for comparison of each
method included the extracted protein concentration and the number of identified
proteins and peptides as well as their phylogenetic, cell localization and
functional distribution and quantitative reproducibility. Furthermore, the
advantage of using specific metagenomes and a 2-step database approach was
illustrated. The results recommend a protocol for protein extraction from
activated sludge based on the protein extraction reagent B-Per and bead beating.
The data have been deposited to the ProteomeXchange with identifier PXD000862
(http://proteomecentral.proteomexchange.org/dataset/PXD000862).
PMID- 25116145
TI - Timing the ischaemic stroke by 1H-MRI: improved accuracy using absolute
relaxation times over signal intensities.
AB - One in four ischaemic stroke patients are ineligible for thrombolytic treatment
due to unknown onset time. Quantification of absolute MR relaxation times and
signal intensities are potential methods for estimating stroke duration. We
compared the accuracy of these approaches and determined whether changes in
relaxation times and signal intensities identify the same ischaemic tissue as
diffusion MRI. Seven Wistar rats underwent permanent middle cerebral artery
occlusion to induce focal ischaemia and were scanned at six time points. The
trace of the diffusion tensor (DAV), T1rho and T2 were acquired at 4.7 T. Results
show relaxation times, and signal intensities of the MR relaxation parameters
increase linearly with ischaemia duration (P<0.001). Using T1rho and T2
relaxation times, an estimate of 4.5 h after occlusion has an uncertainty of +/-
12 and +/- 35 min, respectively, compared with over 50 min for signal
intensities. In addition, we present a pixel-by-pixel method that simultaneously
estimates stroke onset time and identifies potentially irreversible ischaemic
tissue using absolute relaxation times. This method demonstrates signal intensity
changes during ischaemia display an ambiguous pattern and highlights the
possibility that diffusion MRI overestimates the true extent of irreversible
ischaemia. In conclusion, quantification of absolute relaxation times at a single
time point enables a more accurate estimation of stroke duration than signal
intensities and provides more information about tissue status in ischaemia.
PMID- 25116147
TI - Oxidation of nanopores in a silicon membrane: self-limiting formation of sub-10
nm circular openings.
AB - We describe a simple but reliable approach to shrink silicon nanopores with
nanometer precision for potential high throughput biomolecular sensing and
parallel DNA sequencing. Here, nanopore arrays on silicon membranes were
fabricated by a self-limiting shrinkage of inverted pyramidal pores using dry
thermal oxidation at 850 degrees C. The shrinkage rate of the pores with various
initial sizes saturated after 4 h of oxidation. In the saturation regime, the
shrinkage rate is within +/- 2 nm h(-1). Oxidized pores with an average diameter
of 32 nm were obtained with perfect circular shape. By careful design of the
initial pore size, nanopores with diameters as small as 8 nm have been observed.
Statistics of the pore width show that the shrinkage process did not broaden the
pore size distribution; in most cases the distribution even decreased slightly.
The progression of the oxidation and the deformation of the oxide around the
pores were characterized by focused ion beam and electron microscopy. Cross
sectional imaging of the pores suggests that the initial inverted pyramidal
geometry is most likely the determining factor for the self-limiting shrinkage.
PMID- 25116146
TI - A simple repeat polymorphism in the MITF-M promoter is a key regulator of white
spotting in dogs.
AB - The white spotting locus (S) in dogs is colocalized with the MITF (microphtalmia
associated transcription factor) gene. The phenotypic effects of the four S
alleles range from solid colour (S) to extreme white spotting (s(w)). We have
investigated four candidate mutations associated with the s(w) allele, a SINE
insertion, a SNP at a conserved site and a simple repeat polymorphism all
associated with the MITF-M promoter as well as a 12 base pair deletion in exon
1B. The variants associated with white spotting at all four loci were also found
among wolves and we conclude that none of these could be a sole causal mutation,
at least not for extreme white spotting. We propose that the three canine white
spotting alleles are not caused by three independent mutations but represent
haplotype effects due to different combinations of causal polymorphisms. The
simple repeat polymorphism showed extensive diversity both in dogs and wolves,
and allele-sharing was common between wolves and white spotted dogs but was non
existent between solid and spotted dogs as well as between wolves and solid dogs.
This finding was unexpected as Solid is assumed to be the wild-type allele. The
data indicate that the simple repeat polymorphism has been a target for selection
during dog domestication and breed formation. We also evaluated the significance
of the three MITF-M associated polymorphisms with a Luciferase assay, and found
conclusive evidence that the simple repeat polymorphism affects promoter
activity. Three alleles associated with white spotting gave consistently lower
promoter activity compared with the allele associated with solid colour. We
propose that the simple repeat polymorphism affects cooperativity between
transcription factors binding on either flanking sides of the repeat. Thus, both
genetic and functional evidence show that the simple repeat polymorphism is a key
regulator of white spotting in dogs.
PMID- 25116148
TI - Characterisation and mapping of gene Lr73 conferring seedling resistance to
Puccinia triticina in common wheat.
AB - KEY MESSAGE: A gene conferring seedling resistance to Puccinia triticina was
mapped to chromosome 2BS in the wheat Morocco. The gene was shown to be distinct
and was therefore designated Lr73. The wheat genotype Morocco, widely susceptible
to isolates of Puccinia triticina, was resistant to an Australian isolate of this
pathogen collected in 2004. Genetic studies established that the resistance in
Morocco was also present the Australian wheat genotypes Avocet, Halberd, Harrier,
Tincurrin and a selection of cultivar Warigal lacking the resistance gene Lr20.
Genetic studies based on a cross with Halberd showed that the gene is dominant
and located on chromosome 2BS (XwPt8760-4 cM-Lr73-1.4 cM-XwPt8235). The gene was
genetically independent of the Lr13, Lr16 and Lr23 loci, also located on
chromosome 2BS, indicating that it is distinct. The locus designation Lr73 was
therefore assigned. On the basis of multi-pathotype tests, it is likely Lr73 is
also present in the Australian wheat cultivars Clearfield STL, Federation (with
Lr10), Gatcher (with Lr10 and Lr27+Lr31), Marombi (with Lr1 and Lr37), Pugsley
(with Lr1 and Lr37), Spear (with Lr1), Stiletto and Tarsa (with Lr1). Gene Lr73
is unlikely to be of value in resistance breeding. However, recognising Lr73 is
important to avoid its inadvertent selection in breeding programmes. Furthermore,
the apparent rarity of avirulence for genes like Lr73, sometimes referred to as
"fossil" resistance genes, makes them of interest in terms of the evolution of
disease resistance in host plants and of virulence in the respective rust
pathogens.
PMID- 25116149
TI - Synthetic food colours in saffron solutions, saffron rice and saffron chicken
from restaurants in Tehran, Iran.
AB - Saffron solutions, saffron rice and saffron chicken samples were considered for
synthetic colours as additives, which are forbidden according to Iranian national
standards. Samples were taken from restaurants of three locations and analysed by
high-performance liquid chromatography. Of the total 573 samples, 52% were
positive for at least one colour. The most prevalent colours were Tartrazine,
Quinoline Yellow and Sunset Yellow, with 44%, 9.1% and 8.4% of the samples
testing positive for these colours, respectively. Carmoisine and Ponceau were
both detected only in 0.5% of the positive samples and found only in saffron
solution. In conclusion, synthetic food colours, especially Tartrazine should be
regarded as a potential risk in saffron and its related food. Therefore, new
attempts for food safety and quality should be undertaken to eliminate the use of
these colours in restaurants.
PMID- 25116150
TI - Spectroscopic and quantum mechanical investigation of N,N'-bisarylmalonamides:
solvent and structural effects.
AB - The UV absorption spectra of ten N,N'-bisarylmalonamides have been recorded in
the range 200-400 nm in a set of selected solvents. The solute-solvent
interactions have been analyzed on the basis of the linear solvation energy
relationship (LSER) concept proposed by Kamlet and Taft. The effects of
substituents on the absorption spectra have been interpreted by correlating
absorption frequencies with Hammett substituent constants. Furthermore, the
experimental findings have been interpreted using the DFT CAM-B3LYP/6-311+G(d,p)
method. Electronic energies have been calculated using the same method in
combination with the implicit solvation model (conductor-like polarizable
continuum model, CPCM) as well as with the explicit addition of two molecules of
solvent.
PMID- 25116151
TI - Investigation of the torsional barrier of EDOT using molecular mechanics and DFT
methods.
AB - When heterocyclic monomers are polymerized by electrochemical or chemical
methods, they form fully conjugated polymers which have a wide range of
applications due to their outstanding electronic properties. Among this class of
compounds, thiophene derivatives are widely used due to their chemical stability
and synthesis flexibility. With the goal to investigate the torsion barrier of
polymer chains, a few units of 3,4-ethylenedioxythiophene (EDOT) were chosen and
submitted to molecular mechanics (MM), density functional theory (DFT) and
coupled cluster CCSD(T) calculations. This study helps to understand the
performance and transferability of force fields used in molecular mechanics and
molecular dynamics simulations often used to describe structure-property
relationships of those systems. Determination of inter-ring torsion angle was
performed in a comparative study using both force field, DFT and CCSD(T) methods.
A good agreement was noticed between MM and QC results and highlights the
importance of the description of the interactions involving the oxygen atoms
present in the structure of EDOT. These observations are related to the
alpha,alpha-coupling that occurs between the monomer units and yields a linear
polymer. DFT HOMO and LUMO orbitals were also presented. Finally, UV-vis spectra
of EDOT units were obtained using several levels of theory by means of time
dependent DFT calculations (TD-DFT).
PMID- 25116153
TI - Deformation density and energy decomposition to describe interactions between
(eta5-C5H5)M and highly reactive molecules C4H4 and (C3H3)-.
AB - Using DFT calculations, an energy decomposition analysis (EDA) combined with
natural orbitals for chemical valence (NOCV), EDA-NOCV approach was used to
describe the nature of the interaction between eta5-cyclopentadienyl metal
complexes (eta5-C5H5)M, with M=Co, Rh, and cyclobutadiene (Cb) and cyclopropenyl
anion (C3H3)- molecules, which are highly reactive molecules in their free state.
EDA-NOCV draws a covalent picture for these interactions. With this
interpretation of interactions, the character of aromaticity could be the result
of the delocalization of six electrons in pi orbitals of the (eta5-C5H5)M
fragment and Cb/C3H3(-1) ligand. This description of the bonding interaction
might also justify the experimental observation that, in complexes of CpM-Cb
(M=Co, Rh), the viability of the Friedel-Crafts acylation and other electrophilic
substitutions on the four-membered ring is greater than that of the five-membered
ring.
PMID- 25116152
TI - Computational approaches for evaluating the effect of sequence variations and the
intrinsically disordered C-terminal region of the Helicobacter pylori CagA
protein on the interaction with tyrosine kinase Src.
AB - The Helicobacter pylori CagA protein was the first bacterial oncoprotein to be
identified as important in the development of human malignancies such as gastric
cancer. It is not clear how it is able to deregulate a set of cell control
mechanisms to induce carcinogenesis following translocation into human gastric
epithelial cells. It is likely, however, that structural variations in the CagA
sequence alter its affinity with the host proteins inducing differences in the
pathogenicity of different H. pylori strains. Using the recently elucidated N
terminal 3D structure of H. pylori CagA, information on the full cagA gene
sequence, and intrinsically disordered protein structure predictions methods we
evaluated the interaction of different CagA variants with the kinase Src. An
automated docking followed by molecular dynamics simulations were performed to
explore CagA interaction modes with Src, one of its cellular partners. The
computational approach let us establish that even in the presence of the same
number and type of EPIYA motifs, CagA protein can reveal different spatial
distributions. Based on the lowest affinity energy and higher number of
interactions it was established that the principal forces governing the CagA-Src
interaction are electrostatic. Results showed that EPIYA-D models presents higher
affinity with some host proteins than EPIYA-C. Thus, we highlight the importance
and advantage of the use of computational tools in combining chemical and
biological data with bioinformatics for modeling and prediction purposes in some
cases where experimental techniques present limitations.
PMID- 25116158
TI - Laparoscopic repair of recurrent incisional hernia using a 'balloon' for mesh
positioning--a video vignette.
PMID- 25116159
TI - Essential differences in clinical and bone marrow features in BCR/ABL-positive
thrombocythemia compared to thrombocythemia in the BCR/ABL-negative
myeloproliferative neoplasms essential thrombocythemia and polycythemia vera.
PMID- 25116160
TI - [Compliance with treatment in bronchial asthma - supply in everyday conditions of
pulmonology practice. Pneumology 2014; 68: 315-321 Supply of asthma patients with
combination therapy of ICS and LABA - a SHI data analysis. Pneumology 2014; 68:
336-343].
PMID- 25116162
TI - Synthesis and characterization of Ag8(Ge1-x,Snx )(S6-y ,Sey) colloidal
nanocrystals.
AB - A facile colloidal approach to synthesize Ag8 (Ge1-x ,Snx )(S6-y ,Sey )
nanocrystals (NCs) in a highly controlled way across the entire compositional
ranges (0<=x<=1, 0<=y<=6) has been developed. The NCs exhibit a uniform size
distribution, highly crystalline structure, over 1 g scalable synthesis, and
tunable band gaps in the range of 0.88-1.45 eV by varying their chemical
compositions. The Ag8 GeS6 NCs with a band gap of approximately 1.45 eV were
employed as a model light harvester to assess their applicability in solar cells
by a full solution-processing device, yielding an efficiency of 0.28 % under
AM1.5 illumination, demonstrating their application potential in solar energy
utilization.
PMID- 25116161
TI - The genetic basis of variation in clean lineages of Saccharomyces cerevisiae in
response to stresses encountered during bioethanol fermentations.
AB - Saccharomyces cerevisiae is the micro-organism of choice for the conversion of
monomeric sugars into bioethanol. Industrial bioethanol fermentations are
intrinsically stressful environments for yeast and the adaptive protective
response varies between strain backgrounds. With the aim of identifying
quantitative trait loci (QTL's) that regulate phenotypic variation, linkage
analysis on six F1 crosses from four highly divergent clean lineages of S.
cerevisiae was performed. Segregants from each cross were assessed for tolerance
to a range of stresses encountered during industrial bioethanol fermentations.
Tolerance levels within populations of F1 segregants to stress conditions
differed and displayed transgressive variation. Linkage analysis resulted in the
identification of QTL's for tolerance to weak acid and osmotic stress. We tested
candidate genes within loci identified by QTL using reciprocal hemizygosity
analysis to ascertain their contribution to the observed phenotypic variation;
this approach validated a gene (COX20) for weak acid stress and a gene (RCK2) for
osmotic stress. Hemizygous transformants with a sensitive phenotype carried a
COX20 allele from a weak acid sensitive parent with an alteration in its protein
coding compared with other S. cerevisiae strains. RCK2 alleles reveal peptide
differences between parental strains and the importance of these changes is
currently being ascertained.
PMID- 25116164
TI - Limb apraxia and verb processing in Alzheimer's disease.
AB - OBJECTIVE: The present research investigates language and praxis abilities in
patients with Alzheimer's disease in order to study the relationship between
these two cognitive domains. METHOD: The experimental evaluation of patients and
control group performance was designed to permit a direct comparison of
linguistic abilities (i.e., verb and noun naming and sentence comprehension) and
praxic abilities (i.e., gesture execution for complex movements). Moreover, for
the first time, action comprehension was explored using the Action Sequence
Comprehension. RESULTS AND CONCLUSION: Analyses of variance (ANOVAs) and
correlational analyses showed that a direct relationship may exist between
language impairment and apraxia in patients with Alzheimer's disease. In
addition, the production and comprehension of both language and action were
equally impaired in patients, providing further evidence for a spectrum of
concomitant linguistic and praxis deficits in Alzheimer's disease. Finally, the
ability to correctly comprehend action semantics was related more directly to
verb production ability than to noun production.
PMID- 25116165
TI - Pre-B-cell acute lymphoblastic leukemia in a boy with hereditary multiple
exostoses caused by EXT1 deletion.
PMID- 25116163
TI - NRPquest: Coupling Mass Spectrometry and Genome Mining for Nonribosomal Peptide
Discovery.
AB - Nonribosomal peptides (NRPs) such as vancomycin and daptomycin are among the most
effective antibiotics. While NRPs are biomedically important, the computational
techniques for sequencing these peptides are still in their infancy. The recent
emergence of mass spectrometry techniques for NRP analysis (capable of sequencing
an NRP from small amounts of nonpurified material) revealed an enormous diversity
of NRPs. However, as many NRPs have nonlinear structure (e.g., cyclic or branched
cyclic peptides), the standard de novo sequencing tools (developed for linear
peptides) are not applicable to NRP analysis. Here, we introduce the first NRP
identification algorithm, NRPquest, that performs mutation-tolerant and
modification-tolerant searches of spectral data sets against a database of
putative NRPs. In contrast to previous studies aimed at NRP discovery (that
usually report very few NRPs), NRPquest revealed nearly a hundred NRPs (including
unknown variants of previously known peptides) in a single study. This result
indicates that NRPquest can potentially make MS-based NRP identification as
robust as the identification of linear peptides in traditional proteomics.
PMID- 25116166
TI - The Last Bastion of Sexual and Gender Prejudice? Sexualities, Race, Gender,
Religiosity, and Spirituality in the Examination of Prejudice Toward Sexual and
Gender Minorities.
AB - Prior research has reported that many Americans hold prejudicial attitudes toward
sexual and gender minorities. Most of this research analyzed attitudes toward
target categories in isolation and not in relation to attitudes toward
heterosexuals. In addition, most previous research has not examined attitudes of
members of sexual and gender minority categories toward other categories. While
some research has examined the influence of religiosity on attitudes toward
sexual and gender minorities, none of these studies has examined religiosity
while also examining the influence of spirituality. In this article we drew on
insights from queer theory to examine attitudes toward heterosexual, gay,
lesbian, bisexual, and transgender individuals, as well as individuals who
practice polygamy, among college students. Three samples gathered over a four
year period (2009, 2011, 2013) at a private, nonsectarian, midsized urban
university in the Southeastern United States were used. We found that
heterosexuals had the most positive rating, followed in order of rating by
gay/lesbian, bisexual, and transgender individuals, and then those who practice
polygamy. Regression analyses revealed gender and race were significant
predictors of attitudes toward various sexual and gender categories. Holding a
literalistic view of the Bible and self-identifying as more religious were
related to more negative views toward sexual minorities, while self-identifying
as more spiritual was related to more positive views.
PMID- 25116167
TI - Lymphaticovenular anastomosis to prevent cellulitis associated with lymphoedema.
AB - BACKGROUND: One of the complications of lymphoedema is recurrent cellulitis. The
aim was to determine whether lymphaticovenous anastomosis (LVA) was effective at
reducing cellulitis in patients with lymphoedema. METHODS: This was a
retrospective review of patients with arm/leg lymphoedema who underwent LVA. The
frequency of cellulitis was compared before and after surgery. The diagnostic
criteria for cellulitis were a fever of 38.5 degrees C or higher, and
warmth/redness in the affected limb(s). RESULTS: A total of 95 patients were
included. The mean number of episodes of cellulitis in the year preceding surgery
was 1.46, compared with 0.18 in the year after surgery (P < 0.001). CONCLUSION:
LVA reduced the rate of cellulitis in these patients with lymphoedema.
PMID- 25116169
TI - Acute pancreatitis.
PMID- 25116171
TI - Synthesis and electrochemical performance of surface-modified nano-sized
core/shell tin particles for lithium ion batteries.
AB - Tin is able to lithiate and delithiate reversibly with a high theoretical
specific capacity, which makes it a promising candidate to supersede graphite as
the state-of-the-art negative electrode material in lithium ion battery
technology. Nevertheless, it still suffers from poor cycling stability and high
irreversible capacities. In this contribution, we show the synthesis of three
different nano-sized core/shell-type particles with crystalline tin cores and
different amorphous surface shells consisting of SnOx and organic polymers. The
spherical size and the surface shell can be tailored by adjusting the synthesis
temperature and the polymer reagents in the synthesis, respectively. We determine
the influence of the surface modifications with respect to the electrochemical
performance and characterize the morphology, structure, and thermal properties of
the nano-sized tin particles by means of high-resolution transmission electron
microscopy, x-ray diffraction, and thermogravimetric analysis. The
electrochemical performance is investigated by constant current charge/discharge
cycling as well as cyclic voltammetry.
PMID- 25116170
TI - Differential and conditional activation of PKC-isoforms dictates cardiac
adaptation during physiological to pathological hypertrophy.
AB - A cardiac hypertrophy is defined as an increase in heart mass which may either be
beneficial (physiological hypertrophy) or detrimental (pathological hypertrophy).
This study was undertaken to establish the role of different protein kinase-C
(PKC) isoforms in the regulation of cardiac adaptation during two types of
cardiac hypertrophy. Phosphorylation of specific PKC-isoforms and expression of
their downstream proteins were studied during physiological and pathological
hypertrophy in 24 week male Balb/c mice (Mus musculus) models, by reverse
transcriptase-PCR, western blot analysis and M-mode echocardiography for cardiac
function analysis. PKC-delta was significantly induced during pathological
hypertrophy while PKC-alpha was exclusively activated during physiological
hypertrophy in our study. PKC-delta activation during pathological hypertrophy
resulted in cardiomyocyte apoptosis leading to compromised cardiac function and
on the other hand, activation of PKC-alpha during physiological hypertrophy
promoted cardiomyocyte growth but down regulated cellular apoptotic load
resulting in improved cardiac function. Reversal in PKC-isoform with induced
activation of PKC-delta and simultaneous inhibition of phospho-PKC-alpha resulted
in an efficient myocardium to deteriorate considerably resulting in compromised
cardiac function during physiological hypertrophy via augmentation of apoptotic
and fibrotic load. This is the first report where PKC-alpha and -delta have been
shown to play crucial role in cardiac adaptation during physiological and
pathological hypertrophy respectively thereby rendering compromised cardiac
function to an otherwise efficient heart by conditional reversal of their
activation.
PMID- 25116173
TI - Facile immobilization of ag nanocluster on nanofibrous membrane for oil/water
separation.
AB - Superhydrophobic and superoleophilic electrospun nanofibrous membranes exhibiting
excellent oil/water separation performance were green fabricated by a facile
route combining the amination of electrospun polyacrylonitrile (APAN) nanofibers
and immobilization of a Ag nanocluster with an electroless plating technique,
followed by n-hexadecyl mercaptan (RSH) surface modification. By introducing the
hierarchically rough structures and low surface energy, the pristine
superhydrophilic APAN nanofibrous membranes could be endowed with a
superhydrophobicity with water contact angle of 171.1 +/- 2.3 degrees , a
superoleophilicity with oil contact angle of 0 degrees and a self-cleaning
surface arising from the extremely low water contact angle hysteresis (3.0 +/-
0.6 degrees ) and a low water-adhesion property. Surface morphology studies have
indicated that the selective wettability of the resultant membranes could be
manipulated by tuning the electroless plating time as well as the hierarchical
structures. More importantly, the extremely high liquid entry pressure of water
(LEPw, 175 +/- 3 kPa) and the robust fiber morphology of the APAN immobilized Ag
nanocluster endowed the as-prepared membranes with excellent separation
capability and stability for oil/water separation by a solely gravity-driven
process. The resultant membranes exhibited remarkable separation efficiency in
both hyper-saline environment and broad pH range conditions, as well as excellent
recyclability, which would make them a promising candidate for industrial oil
contaminated water treatments and marine spilt oil cleanup, and provided a new
prospect to achieve functional nanofibrous membranes for oil/water separation.
PMID- 25116172
TI - Synergistic effect of Aspergillus niger and Trichoderma reesei enzyme sets on the
saccharification of wheat straw and sugarcane bagasse.
AB - Plant-degrading enzymes can be produced by fungi on abundantly available low-cost
plant biomass. However, enzymes sets after growth on complex substrates need to
be better understood, especially with emphasis on differences between fungal
species and the influence of inhibitory compounds in plant substrates, such as
monosaccharides. In this study, Aspergillus niger and Trichoderma reesei were
evaluated for the production of enzyme sets after growth on two "second
generation" substrates: wheat straw (WS) and sugarcane bagasse (SCB). A. niger
and T. reesei produced different sets of (hemi-)cellulolytic enzymes after growth
on WS and SCB. This was reflected in an overall strong synergistic effect in
releasing sugars during saccharification using A. niger and T. reesei enzyme
sets. T. reesei produced less hydrolytic enzymes after growth on non-washed SCB.
The sensitivity to non-washed plant substrates was not reduced by using CreA/Cre1
mutants of T. reesei and A. niger with a defective carbon catabolite repression.
The importance of removing monosaccharides for producing enzymes was further
underlined by the decrease in hydrolytic activities with increased glucose
concentrations in WS media. This study showed the importance of removing
monosaccharides from the enzyme production media and combining T. reesei and A.
niger enzyme sets to improve plant biomass saccharification.
PMID- 25116174
TI - Fumonisins B1 and B2 in maize harvested in Hebei province, China, during 2011
2013.
AB - A total of 125 maize kernel samples were collected from Hebei province in China
during 2011-2013 and were analysed for incidence and contamination levels of
fumonisins (FB1 + FB2) by HPLC with fluorescence detection. The incidence of FBs
for all samples was 46.4%. The mean contamination level of FBs for the samples
collected in 2013 was 706 MUg kg-1, which was higher than the levels in 2012 (429
MUg kg-1) and 2011 (250 MUg kg-1). All samples, except five, exhibited total FB
levels below 4000 MUg kg-1, which is the maximum limit as set by the European
Commission. The probable daily intakes of FBs (0.04 in 2011; 0.07 in 2012; 0.12
in 2013, expressed as MUg kg-1 body weight/day) were all within the provisional
maximum tolerable daily intake of 2.0 MUg kg-1 of body weight/day as set by the
Joint FAO/WHO Expert Committee on Food Additives. Nevertheless, monitoring is
needed to prevent and control the potential risk of FB exposure to the consumers.
PMID- 25116180
TI - Laparoscopic anterior resection in a patient with situs inversus--a video
vignette.
PMID- 25116181
TI - [Decreasing dementia incidence rates? Implications for public health and
prevention].
PMID- 25116175
TI - The coactivator PGC-1alpha regulates skeletal muscle oxidative metabolism
independently of the nuclear receptor PPARbeta/delta in sedentary mice fed a
regular chow diet.
AB - AIMS/HYPOTHESIS: Physical activity improves oxidative capacity and exerts
therapeutic beneficial effects, particularly in the context of metabolic
diseases. The peroxisome proliferator-activated receptor (PPAR) gamma coactivator
1alpha (PGC-1alpha) and the nuclear receptor PPARbeta/delta have both been
independently discovered to play a pivotal role in the regulation of oxidative
metabolism in skeletal muscle, though their interdependence remains unclear.
Hence, our aim was to determine the functional interaction between these two
factors in mouse skeletal muscle in vivo. METHODS: Adult male control mice, PGC
1alpha muscle-specific transgenic (mTg) mice, PPARbeta/delta muscle-specific
knockout (mKO) mice and the combination PPARbeta/delta mKO + PGC-1alpha mTg mice
were studied under basal conditions and following PPARbeta/delta agonist
administration and acute exercise. Whole-body metabolism was assessed by indirect
calorimetry and blood analysis, while magnetic resonance was used to measure body
composition. Quantitative PCR and western blot were used to determine gene
expression and intracellular signalling. The proportion of oxidative muscle fibre
was determined by NADH staining. RESULTS: Agonist-induced PPARbeta/delta
activation was only disrupted by PPARbeta/delta knockout. We also found that the
disruption of the PGC-1alpha-PPARbeta/delta axis did not affect whole-body
metabolism under basal conditions. As expected, PGC-1alpha mTg mice exhibited
higher exercise performance, peak oxygen consumption and lower blood lactate
levels following exercise, though PPARbeta/delta mKO + PGC-1alpha mTg mice showed
a similar phenotype. Similarly, we found that PPARbeta/delta was dispensable for
PGC-1alpha-mediated enhancement of an oxidative phenotype in skeletal muscle.
CONCLUSIONS/INTERPRETATION: Collectively, these results indicate that
PPARbeta/delta is not an essential partner of PGC-1alpha in the control of
skeletal muscle energy metabolism.
PMID- 25116182
TI - Aspirin-responsive, migraine-like transient cerebral and ocular ischemic attacks
and erythromelalgia in JAK2-positive essential thrombocythemia and polycythemia
vera.
AB - Migraine-like cerebral transient ischemic attacks (MIAs) and ocular ischemic
manifestations were the main presenting features in 10 JAK2(V617F)-positive
patients studied, with essential thrombocythemia (ET) in 6 and polycythemia vera
(PV) in 4. Symptoms varied and included cerebral ischemic attacks, mental
concentration disturbances followed by throbbing headaches, nausea, vomiting,
syncope or even seizures. MIAs were frequently preceded or followed by ocular
ischemic events of blurred vision, scotomas, transient flashing of the eyes, and
sudden transient partial blindness preceded or followed erythromelalgia in the
toes or fingers. The time lapse between the first symptoms of aspirin-responsive
MIAs and the diagnosis of ET in 5 patients ranged from 4 to 12 years. At the time
of erythromelalgia and MIAs, shortened platelet survival, an increase in the
levels of the platelet activation markers beta-thromboglobulin and platelet
factor 4 and also in urinary thromboxane B2 were clearly indicative of the
spontaneous in vivo platelet activation of constitutively JAK2(V617F)-activated
thrombocythemic platelets. Aspirin relieves the peripheral, cerebral and ocular
ischemic disturbances by irreversible inhibition of platelet cyclo-oxygenase (COX
1) activity and aggregation ex vivo. Vitamin K antagonist, dipyridamole,
ticlopidine, sulfinpyrazone and sodium salicylate have no effect on platelet COX
1 activity and are ineffective in the treatment of thrombocythemia-specific
manifestations of erythromelalgia and atypical MIAs. If not treated with aspirin,
ET and PV patients are at a high risk of major arterial thrombosis including
stroke, myocardial infarction and digital gangrene.
PMID- 25116183
TI - Antimicrobial Constituents of the Mature Carpels of Manglietiastrum sinicum.
AB - Seven new compounds, including a eupodienone-type lignan (1), a
dibenzocyclooctadiene-type lignan (2), three tetrahydrofuran-type lignans (3-5),
and two 1-phenylbutyl benzoates (6, 7), together with six known compounds, were
isolated from the mature carpels of Manglietiastrum sinicum. The structures of
new compounds 1-7 were defined by spectroscopic techniques, and the absolute
configuration of manglisin A (1) was determined by X-ray crystallography.
Compounds 1-4 exhibited moderate antimicrobial activities (MIC values: 0.016-0.14
MUM) against Staphylococcus aureus, MRSA 82(#), MRSA 92(#), MRSA 98(#), and MRSA
331(#). Compounds 2 and 3 showed weak cytotoxic activity against five human tumor
cell lines.
PMID- 25116184
TI - Factors associated with recommitment of NGRI acquittees to a forensic hospital.
AB - The current archival study assesses risk factors associated with recommitment of
142 individuals adjudicated Not Guilty by Reason of Insanity (NGRI) from civil
settings to a forensic hospital in New York State. Within 10 years of transfer
from a forensic hospital, 40 (28.2%) were recommitted. Using survival analyses to
account for the wide range in opportunity for recommitment, period of transfer
(i.e., pre versus post the 1995 case of George L, which clarified factors related
to assessments of dangerousness) and the Historical scale and specific items of
the HCR-20 emerged as important risk factors for recommitment. Specifically,
hazard of recommitment was 2.9 times higher for those with high Historical scores
as compared to those with low scores. However, few individual risk factors were
associated with recommitment. Prior supervision failure, negative attitude,
problems with substance use, and absent or less serious major mental illness and
relationship problems were informative in predicting recommitment over 10 and 3
year follow-up periods.
PMID- 25116185
TI - An efficient rose bengal based nanoplatform for photodynamic therapy.
AB - Organically modified mesoporous silica nanoparticles (MSNs) containing rose
bengal (RB), a xanthene dye, were successfully synthesized. RB-modified MSNs have
shown a relevant photostability and a high efficiency in the photoproduction and
delivery of singlet oxygen ((1)O2), which is particularly promising for
photodynamic therapy (PDT) applications. In vitro tests have evidenced that RB
MSNs are able to reduce cell proliferation in one of the most aggressive skin
cancer types (SK-MEL-28) after green-light irradiation.
PMID- 25116186
TI - Laboratory surveillance of dengue in Rio Grande do Sul, Brazil, from 2007 to
2013.
AB - BACKGROUND: According to official records, dengue was introduced in Brazil in the
80's; since then several epidemics have occurred. Meanwhile, in Rio Grande do Sul
(RS, Southern Brazil) the first autochthonous case occurred only in 2007.
METHODOLOGY AND PRINCIPAL FINDINGS: In this study we report laboratory
surveillance of dengue cases and seasonality of positive cases, describe
serotypes and characterize the epidemiological pattern of dengue in RS from 2007
to 2013. A total of 9,779 serum samples from patients with suspected dengue fever
were collected and submitted to molecular and/or serological analyses for dengue
virus identification and serotyping, based on viral isolation, NS1 antigen
detection and qRT-PCR, or Dengue IgM capture ELISA and MAC-ELISA. The first
autochthonous dengue case in RS was confirmed in 2007 (DENV-3). While in 2008 and
2009 only imported cases were registered, autochthonous infection waves have been
occurring since 2010. The highest number of dengue infections occurred in 2010,
with DENV-1 and DENV-2 outbreaks in Northwestern RS. In 2011, another DENV-1 and
DENV-2 outbreak occurred in the Northwestern region; moreover, DENV-4 was
detected in travelers. In 2012, DENV-1 and DENV-4 co-circulated. DENV-2
circulation was only detected again in 2013, in high frequency (56.7%), co
circulating with DENV-4 (35%). Most infections occur in adults during summer.
Differences in prevalence between genders were observed in 2007 (60% females),
2008 (60.8% males) and 2009 (77.5% males). CONCLUSIONS: According to results of
dengue surveillance, there was an increase in the number of dengue cases in RS
and of cities infested with Aedes aegypti, possibly as a consequence of
introduction of new serotypes and the difficulty of health programs to control
the vector.
PMID- 25116187
TI - Impact of TCF3 rearrangement on CNS relapse in egyptian pediatric acute
lymphoblastic leukemia.
AB - BACKGROUND: TCF3 rearrangement mostly t(1;19) (q23;p13)/ TCF3-PBX1 gene is
associated with favorable outcome in acute lymphoblastic leukemia (ALL) upon
treatment with intensification protocols; however, it is associated with higher
incidence of central nervous system (CNS) relapse which may affect outcome of
patients. OBJECTIVES: We aimed to assess TCF3 rearrangement in newly diagnosed
pediatric ALL patients in relation to clinical and laboratory parameters, CNS
relapse, and clinical outcome. PATIENTS AND METHODS: Eighty newly diagnosed
pediatric ALL patients following at Pediatric Hematology Oncology Clinic, Ain
Shams University Hospitals were included in this study. Their ages ranged from
0.75 to 16 years. Seventy six (95%) patients had B-lineage ALL and four (5%) had
T-lineage ALL. Data recorded included; age, sex, extramedullary manifestations,
CNS, and testes infiltrations, risk stratification, response to treatment, and
CBC and BM findings. TCF3 rearrangement was assessed by FISH technique using dual
color break-apart probe. RESULTS: TCF3 rearrangement [t(1;19) (q23;p13)] was
detected in 16 (20%) out of the 80 studied patients, and it was significantly
associated with splenomegaly, lymphadenopathy, CNS infiltration at presentation,
high total leucocytic count, low platelet count, high-risk group, and isolated
CNS relapse. These results identify a group of high-risk ALL patients with high
incidence of CNS relapse and poor response to standard therapeutic regimen.
CONCLUSION: Analysis of TCF3 rearrangement [t(1;19) (q23;p13)] at diagnosis may
provide a valuable target for modified and intensified CNS-directed
chemotherapeutic protocol aiming to improve the patients' outcome.
PMID- 25116188
TI - Recent declines in nonmarital childbearing in the United States.
AB - There were sharp increases in nonmarital childbearing from 2002 to 2007,
following the steady increases beginning in the 1980s. The upward trends have
mainly reversed since 2007-2008. In addition, the nature of nonmarital
childbearing may be changing as cohabiting unions have increased over the last
few decades in the United States along with pregnancies within those unions.
Births to unmarried women are at greater risk for adverse outcomes, including low
birth weight, preterm birth, and infant mortality. Social and financial supports
for unmarried mothers may be limited. This report describes recent trends in
nonmarital births from the National Vital Statistics System (NVSS) and in
cohabitation for unmarried mothers using data from the National Survey of Family
Growth (NSFG).
PMID- 25116189
TI - Efficient synthesis of conformationally constrained, amino-triazoloazepinone
containing di- and tripeptides via a one-pot Ugi-Huisgen tandem reaction.
AB - Herein we describe a catalyst-free procedure employing an Ugi-4CR between a beta
azido-alpha-amino acid, propargylamine, an isocyanide and an aldehyde, followed
by a thermal azide-alkyne Huisgen cycloaddition to generate a 16-member library
of amino-triazoloazepinone-bearing di- and tripeptides with up to four points of
diversification and high atom economy.
PMID- 25116190
TI - Implementation of an acute surgical admission ward.
AB - BACKGROUND: The aim of the study was to assess the impact of an acute surgical
admission ward on admission and discharge processes. METHODS: This prospective
cohort study was conducted in a university tertiary referral centre. All acute
surgical patients were clustered in the acute surgical unit (ASU) in February and
March 2012, and discharged or transferred to specialized departments within 48 h.
The primary outcome was length of hospital stay (LOS). Secondary outcomes were
impact on emergency department waiting times, discharge home within 48 h,
incorrect ward admissions, readmissions and mortality. Outcomes of the study
group were compared with those of a historical reference group admitted during
the same interval the year before. RESULTS: Some 249 patients were admitted to
the ASU during the study interval. The reference group consisted of 211 patients.
The total LOS decreased significantly from a median of 4.0 to 2.0 days (P =
0.004). The percentage of patients who were discharged within 48 h increased from
30.3 to 43.4 per cent (P = 0.004). The rate of incorrect ward admission decreased
from 9.5 to 0 per cent. Emergency department waiting time, readmission rate and
30-day mortality did not change. CONCLUSION: Introduction of an acute surgical
unit-shortened length of hospital stay without comprising readmission and
mortality rates.
PMID- 25116191
TI - Duration of luteal support after IVF is important, so why is there no consistency
in practice? The results of a dynamic survey of practice in the United Kingdom.
AB - Luteal support is considered as an essential component of IVF treatment following
ovarian stimulation and embryo transfer. Several studies have consistently
demonstrated a benefit of luteal support compared with no treatment and whilst a
number of preparations are available, no product has been demonstrated as
superior. There is an emerging body of evidence which suggests that extension of
luteal support beyond biochemical pregnancy does not confer a benefit in terms of
successful pregnancy outcome. We performed two surveys separated by 5 years of
practice evolution, with the latter reporting on the use of luteal support in all
IVF clinics in the UK. All clinics reported utilising luteal support with the
majority favouring the use of Cyclogest 400 mg twice daily. In contrast, there
was no consensus on the optimal duration of luteal support. Whilst 24% of clinics
withdrew luteal support at biochemical confirmation of pregnancy, 40% continued
treatment until 12 weeks gestation. Several clinics even extended luteal support
beyond 12 weeks gestation. We observed no difference in practice based on the
size of the IVF unit or treatment funding source. Although there was some change
in practice between surveys in many clinics, there was no uniformity in the
direction of change.
PMID- 25116192
TI - Global Toll-like receptor 4 knockout results in decreased renal inflammation,
fibrosis and podocytopathy.
AB - BACKGROUND AND PURPOSE: Type 1 diabetes mellitus (T1DM) is a pro-inflammatory
state with increased toll-like receptor (TLR) activity. Inflammation is crucial
in diabetic nephropathy (DN). We tested the effect of global deficiency of TLR4
on renal inflammation, fibrosis and podocytopathy using control (C) and
streptozotocin (STZ) induced diabetic wildtype (WT) and TLR4-knockout (TLR4KO)
mice. METHODS: Following STZ treatment, mice were euthanized at 17weeks and
plasma and kidneys collected. RESULTS: Compared to C, STZ-WT mice had
significantly increased macrophage and TLR4 immunostaining in kidney, significant
increases in MyD88, Interferon Regulatory Factor-3, NFKappaB activity, TNF-Alpha,
IL-6, and MCP-1; all these were significantly decreased in the STZ-TLR4KO
compared to STZ-WT mice. Compared to C, there were significant increases in
fibrosis markers (collagen 4, and transforming growth factor-beta) in STZ-WT
which were significantly decreased in the STZ-TLR4KO versus STZ-WT. Podocyte
numbers and podocin were decreased in the STZ-WT versus C and increased in the
STZ-TLR4KO mice. CONCLUSION: Global genetic deficiency of TLR4 also ameliorates
renal inflammation, fibrosis and podocytopathy and could be important in DN.
PMID- 25116193
TI - The Drosophila nephrocyte has a glomerular filtration system.
PMID- 25116194
TI - Reply: Nephrons are generated via a series of committed progenitors.
PMID- 25116196
TI - Size tunable synthesis of solution processable diamond nanocrystals.
AB - Diamond nanocrystals were synthesized catalyst-free from nanoporous carbon at
high pressure and high temperature (HPHT). The synthesized nanocrystals have
tunable diameters between 50 and 200 nm. The nanocrystals are dispersible in
organic solvents such as acetone and are isotropic in nature as seen by dynamic
light scattering.
PMID- 25116195
TI - Taking a call is facilitated by the multisensory processing of smartphone
vibrations, sounds, and flashes.
AB - Many electronic devices that we use in our daily lives provide inputs that need
to be processed and integrated by our senses. For instance, ringing, vibrating,
and flashing indicate incoming calls and messages in smartphones. Whether the
presentation of multiple smartphone stimuli simultaneously provides an advantage
over the processing of the same stimuli presented in isolation has not yet been
investigated. In this behavioral study we examined multisensory processing
between visual (V), tactile (T), and auditory (A) stimuli produced by a
smartphone. Unisensory V, T, and A stimuli as well as VA, AT, VT, and trisensory
VAT stimuli were presented in random order. Participants responded to any
stimulus appearance by touching the smartphone screen using the stimulated hand
(Experiment 1), or the non-stimulated hand (Experiment 2). We examined violations
of the race model to test whether shorter response times to multisensory stimuli
exceed probability summations of unisensory stimuli. Significant violations of
the race model, indicative of multisensory processing, were found for VA stimuli
in both experiments and for VT stimuli in Experiment 1. Across participants, the
strength of this effect was not associated with prior learning experience and
daily use of smartphones. This indicates that this integration effect, similar to
what has been previously reported for the integration of semantically meaningless
stimuli, could involve bottom-up driven multisensory processes. Our study
demonstrates for the first time that multisensory processing of smartphone
stimuli facilitates taking a call. Thus, research on multisensory integration
should be taken into consideration when designing electronic devices such as
smartphones.
PMID- 25116197
TI - Nanotube liquid crystal elastomers: photomechanical response and flexible energy
conversion of layered polymer composites.
AB - Elastomeric composites based on nanotube liquid crystals (LCs) that preserve the
internal orientation of nanotubes could lead to anisotropic physical properties
and flexible energy conversion. Using a simple vacuum filtration technique of
fabricating nanotube LC films and utilizing a transfer process to poly (dimethyl)
siloxane wherein the LC arrangement is preserved, here we demonstrate unique and
reversible photomechanical response of this layered composite to excitation by
near infra-red (NIR) light at ultra-low nanotube mass fractions. On excitation by
NIR photons, with application of small or large pre-strains, significant
expansion or contraction of the sample occurs, respectively, that is continuously
reversible and three orders of magnitude larger than in pristine polymer.
Schlieren textures were noted in these LC composites confirming long range
macroscopic nematic order of nanotubes within the composites. Order parameters of
LC films ranged from S(optical) = 0.51-0.58 from dichroic measurements. Film
concentrations, elastic modulus and photomechanical stress were all seen to be
related to the nematic order parameter. For the same nanotube concentration, the
photomechanical stress was almost three times larger for the self-assembled LC
nanotube actuator compared to actuator based on randomly oriented carbon
nanotubes. Investigation into the kinetics of photomechanical actuation showed
variation in stretching exponent beta with pre-strains, concentration and
orientation of nanotubes. Maximum photomechanical stress of ~ 0.5 MPa W(-1) and
energy conversion of ~ 0.0045% was achieved for these layered composites. The
combination of properties, namely, optical anisotropy, reversible mechanical
response to NIR excitation and flexible energy conversion all in one system
accompanied with low cost makes nanotube LC elastomers important for soft
photochromic actuation, energy conversion and photo-origami applications.
PMID- 25116198
TI - Impact of high ytterbium(III) concentration in the shell on upconversion
luminescence of core-shell nanocrystals.
AB - After coating 20 Yb/2 Er:NaGdF4 core nanocrystals with a NaYbF4 shell,
upconversion emission of the rare earth ions weakens. So far, the exact reason
for this phenomenon is still unclear due to lack of the direct evidence. In this
report, a core@shell@shell sandwich-like structure is designed and fabricated to
investigate this phenomenon. We find that high Yb(3+) concentration in the shell
has mainly two adverse impacts: it promotes not only the deleterious back energy
transfer from Er(3+) in the core to Yb(3+) in the shell but also the energy
transfer from Yb(3+) in the core to Yb(3+) in the shell. To obtain nanocrystals
with high upconversion efficency, appropriate Yb(3+) concentration should be
introduced into the shell or the transition layer.
PMID- 25116199
TI - Movable magnetic porous cores enclosed within carbon microcapsules: structure
controlled synthesis and promoted carbon-based applications.
AB - Rattle-type porous carbon microcapsules (RPCMs) were deliberately designed to
combine multiple functions with the aim of improving the applicability of
amorphous carbon in a synergistic fashion. A movable Fe3O4 nanocluster coated
with porous carbon is encapsulated in the cavity of a carbon microcapsule with an
eggshell-like characteristic, allowing for storage, adsorption, and exchange of
matters through the mesoporous channels of the carbon layer. The synthetic
strategy of RPCMs is flexible and universal, involving the constitution and
carbonization of Fe3O4@PF@PS@PF template particles. This results in a double
carbon shell and a sandwiched hollow cavity with a movable magnetic core. There
is evidence that RPCMs possess large surface areas, hierarchical pore sizes,
hydrophobicity, and magnetic responsiveness. Hence, diverse applications have
been investigated. It is proved that RPCMs exhibit excellent performance in the
effective enrichment of peptides/proteins. The detection limit toward peptides
could reach as low as 10 nM, and the enrichment capacity toward MYO protein is as
high as 410 mg/g (protein/beads). Furthermore, RPCMs are able to harvest proteins
in complex real samples such as fetal bovine serum and rabbit blood. In addition,
RPCMs could be fabricated in a supercapacitor electrode and display outstanding
energy-storage performance. The electrochemical measurements demonstrate that
RPCM-based electrodes have a specific capacitance of as high as 216 F/g (0.1
A/g), long-term cycling stability with a capacitance retention of 92.4% over 1000
cycles (0.2 A/g), and good electronic conductivity.
PMID- 25116200
TI - Development of a novel protocol for generating flavivirus reporter particles.
AB - Infection with West Nile virus (WNV), a mosquito-borne flavivirus, is a growing
public and animal health concern worldwide. Prevention, diagnosis and treatment
strategies for the infection are urgently required. Recently, viral reverse
genetic systems have been developed and applied to clinical WNV virology. We
developed a protocol for generating reporter virus particles (RVPs) of WNV with
the aim of overcoming two major problems associated with conventional protocols,
the difficulty in generating RVPs due to the specific skills required for
handling RNAs, and the potential for environmental contamination by antibiotic
resistant genes encoded within the genome RNA of the RVPs. By using the proposed
protocol, cells were established in which the RVP genome RNA is replicated
constitutively and does not encode any antibiotic-resistant genes, and used as
the cell supply for RVP genome RNA. Generation of the WNV RVPs requires only the
simple transfection of the expression vectors for the viral structural proteins
into the cells. Therefore, no RNA handling is required in this protocol. The WNV
RVP yield obtained using this protocol was similar that obtained using the
conventional protocol. According to these results, the newly developed protocol
appears to be a good alternative for the generation of WNV RVPs, particularly for
clinical applications.
PMID- 25116201
TI - Establishment and application of a multiplex PCR for rapid and simultaneous
detection of six viruses in swine.
AB - A multiplex PCR assay was developed and evaluated subsequently for its
effectiveness in simultaneously detecting mixed viral infections of swine.
Specific primers were designed and used for testing the six swine viruses: three
DNA viruses, including pseudorabies virus (PRV), porcine parvovirus (PPV), and
porcine circovirus type 2 (PCV2); three common RNA viruses, including porcine
reproductive and respiratory syndrome virus (PRRSV), classical swine fever virus
(CSFV), and Japanese encephalitis virus (JEV). This technique has shown to be
highly sensitive in that the minimum detection amounts of nucleic acids from PRV,
PPV, PCV2, PRRSV, CSFV, and JEV were 6.6, 96, 12.9, 10.5, 51, and 46 pg,
respectively. It also was effective for detecting one or multiple viruses in the
specimens, such as the lungs, spleens, lymph nodes, and tonsils collected from
clinically ill pigs. The multiplex PCR method can detect simultaneously not only
infection of the six viruses, but also other swine DNA and RNA viruses. Given its
rapidity, specificity, and sensitivity, the multiplex PCR is a useful tool for
diagnosing clinically the mixed infections of swine DNA and RNA viruses.
PMID- 25116202
TI - A degenerate pair of primers for simultaneous detection of four alpha- and
betanecroviruses.
AB - The high infection levels due to Olive latent virus 1 (OLV-1), Olive mild mosaic
virus (OMMV) (alphanecrovirus) and Tobacco necrosis virus D (TNV-D)
(betanecrovirus) in Portuguese olive orchards prompted us to develop a rapid PCR
based assay for the simultaneous detection of these viruses aimed at the sanitary
selection and marketing of plant material in compliance with European Union
regulations. A pair of degenerate oligonucleotide primers, parRdRp5' and
parCoat3' was designed based on conserved regions located in the RNA-dependent
RNA polymerase (RdRp) and coat protein (CP) genes of these viruses and one other
alphanecrovirus, Tobacco necrosis virus A. Its use in RT-PCR assays generated a
product of ca. 2000 bp for the 4 viral species tested. These primers were
compared with virus specific primers in multiplex RT-PCR, and identical results
were obtained. Its application to dsRNA extracted from 54 olive field growing
trees originated the expected ca. 2000 bp amplicon in 17 trees. The virus
identity was determined by sequencing the cloned RT-PCR products. No TNV-A was
found. The RT-PCR assay using the degenerate primers described in this study were
shown to be reliable in detecting any of the above-mentioned alpha- and
betanecroviruses, and it is as sensitive as that which uses virus specific
primers in multiplex assays. Therefore, this assay is well suited for the rapid
screen of virus-free plant material in selection and improvement crop programmes.
Additionally, it has the potential to reveal virus diversity and the presence of
new viruses, provided the RT-PCR generated amplicon is further sequenced.
PMID- 25116204
TI - Cloacal defect repair--a video vignette.
PMID- 25116203
TI - Prevalence and risk factors for suicidal behavior in young people presenting with
first-episode psychosis in Hong Kong: a 3-year follow-up study.
AB - PURPOSE: Individuals with first-episode psychosis (FEP) have markedly elevated
risk for suicide. Previous research investigating risk factors of suicidal
behavior in FEP mainly focused on western populations. This study aimed to
examine the prevalence, and pretreatment and early illness predictors of suicidal
behavior in Chinese FEP patients. METHOD: Seven hundred participants aged 15-25
years consecutively enrolled in a territory-wide treatment program for FEP in
Hong Kong from July 2001 to August 2003 were studied. Baseline and 3-year follow
up variables were collected via systematic medical file review. Suicidal behavior
evaluated in this study comprised suicide attempt and completed suicide. RESULTS:
Seventy-four (10.6%) participants attempted suicide before treatment. Ten percent
(n = 70) exhibited suicidal behavior and 1% (n = 7) committed suicide during 3
year follow-up. The majority of post-treatment suicidal behaviors (51.4%)
occurred in the first year of follow-up. Jumping from a height was the most
common method of committing suicide. Multivariate regression analysis indicated
that previous suicide attempt, history of substance abuse and poorer baseline
functioning were significantly associated with an increased risk for suicidal
behavior after treatment initiation. CONCLUSION: In a large representative cohort
of Chinese young FEP patients, the rates of suicidal behavior before and after
treatment and risk factors for post-treatment suicidal behavior were comparable
to the findings of previous research on early psychosis conducted in western
populations. Close monitoring of high-risk patients with history of attempted
suicide or substance abuse, and enhancement of psychosocial functioning may help
reduce suicide risk in the early stage of psychotic illness.
PMID- 25116205
TI - Attaining khinem: challenges, coping strategies and resilience among Eveny
adolescents in northeastern Siberia.
AB - This article examines challenges, coping strategies, and resilience among Eveny
adolescents in northeastern Siberia. It explores situations which the study
participants associate with challenge and hardship, namely their experiences of
transition from life in the family reindeer herding camp to schooling at the age
of 7, bullying, boredom, and violence. By situating the data within the Eveny
framework of resilience (khinem), the study provides the ethnographic context for
coping strategies and efforts (e.g., sharing, inter- and intragenerational
support, availability of safe homes) undertaken by the community in order to
mitigate the situations of risk and hardship and to facilitate adolescents'
resilience. The account emphasizes that instead of identifying adolescents as
either resilient or vulnerable, it is necessary to explore culturally specific
processes and practices which potentially contribute to their acquisition of
resilience.
PMID- 25116207
TI - Concussion 101 for SLPs.
PMID- 25116208
TI - Medical treatment of concussion.
AB - A concussion is a brain injury, a change in function induced by traumatic forces.
The incidence of concussion is increasing, likely due to increased awareness and
improvement in recognition. Speech and language pathology professionals working
in schools may encounter patients who have suffered concussions. At the root of
concussion pathophysiology is altered metabolism and an acquired energy deficit.
The mainstay of treatment for concussion is cognitive and physical rest, allowing
for normalization of the metabolism and correction of the energy deficit. Once
recovered, the student may need accommodations to successfully return to school
without added difficulty and should follow a return to play protocol to return to
athletics safely.
PMID- 25116209
TI - Neurometabolic aspects of sports-related concussion.
AB - Concussion is a transitory brain injury resulting from a blow to the head.
Concussion is considered a mild traumatic brain injury (mTBI), which is self
limited. Repetitive mTBI has been associated with chronic, progressive neurologic
damage. Extreme biochemical changes occur in neuron cells as a result of mTBI.
These metabolic disturbances may reflect the symptoms observed in patients who
had concussions. However, it has been difficult to match clinical signs and
symptoms. Currently, there is no test to diagnose concussion. Further studies are
needed to elucidate the biochemical details of the metabolic cascade and the
associated time frame, which will help determine when an athlete can safely
return to the game.
PMID- 25116206
TI - Collagen can selectively trigger a platelet secretory phenotype via glycoprotein
VI.
AB - Platelets are not only central actors of hemostasis and thrombosis but also of
other processes including inflammation, angiogenesis, and tissue regeneration.
Accumulating evidence indicates that these "non classical" functions of platelets
do not necessarily rely on their well-known ability to form thrombi upon
activation. This suggests the existence of non-thrombotic alternative states of
platelets activation. We investigated this possibility through dose-response
analysis of thrombin- and collagen-induced changes in platelet phenotype, with
regards to morphological and functional markers of platelet activation including
shape change, aggregation, P-selectin and phosphatidylserine surface expression,
integrin activation, and release of soluble factors. We show that collagen at low
dose (0.25 ug/mL) selectively triggers a platelet secretory phenotype
characterized by the release of dense- and alpha granule-derived soluble factors
without causing any of the other major platelet changes that usually accompany
thrombus formation. Using a blocking antibody to glycoprotein VI (GPVI), we
further show that this response is mediated by GPVI. Taken together, our results
show that platelet activation goes beyond the mechanisms leading to platelet
aggregation and also includes alternative platelet phenotypes that might
contribute to their thrombus-independent functions.
PMID- 25116210
TI - Community-based resources for concussion management.
AB - Speech-language pathologists can serve an important role as members of
interdisciplinary treatment teams in the rehabilitation of concussion-related
cognitive-communicative changes in the community setting. This article discusses
the continuum of care for individuals who have experienced concussion and the
importance of appropriate assessment and functionally based intervention. Factors
such as executive function impairments, sensory overload, and cognitive exertion
can yield subtle deficits that can impact functional return to work or school.
Community resources such as support groups are discussed, as well as the impact
of state and federal policies related to concussion on community activities.
PMID- 25116211
TI - Clinical test instrument development to identify and track recovery from
concussion.
AB - Over the past 25 years, neuropsychological assessment has been the prominent
clinical method for evaluating neurocognitive functioning and monitoring recovery
following mild traumatic brain injury (mTBI), or concussion. During this time,
neuropsychological assessment of concussion has developed extensively starting
from traditional paper-and-pencil tests to the more current computerized
assessment batteries that are specifically designed for evaluating mTBI.
Concussion assessment is complex and challenging due to the highly variable
neurocognitive behavior and the wide range of diverse symptoms that follow an
injury. Therefore, neuropsychological testing is only one component of a
multifaceted, comprehensive assessment approach that also includes balance
testing and symptom assessment. Because concussions may go undetected, more
emphasis has been placed on objective and sensitive neuropsychological measures.
Factors that could affect the validity of test performance include athletes not
recognizing or intentionally hiding their symptoms or sandbagging their baseline
performance. Due to the complex nature of identifying and evaluating mild head
injuries, the purpose of this review is to discuss (1) the clinical use of
neuropsychological testing in concussion management, (2) the methods used for
evaluating and monitoring recovery following concussion, (3) the characteristics
of current assessment instruments, and (4) additional clinical factors and
approaches for concussion assessment and management.
PMID- 25116212
TI - Clinical assessment of balance in adults with concussion.
AB - Balance is a key component to the assessment of concussion injury; however, the
efficacies of clinical tests used are currently under debate. It is questionable
whether currently accepted methods of standing balance assessment quantify
balance disturbances sufficiently to support decisions on recovery and return to
play. Recent evidence of balance abnormalities postconcussion that linger beyond
the typical 3- to 5-day recovery period support arguments that currently
available standing balance tests are not sensitive enough to determine recovery
of function. This article discusses the current clinical tests used in the
assessment of concussion in adults and their limitations and the evidence
supporting continued balance dysfunction. Implications for the future of balance
assessment in concussed adults and recommendations to clinicians for best
practices are presented.
PMID- 25116213
TI - Pharmacological management of traumatic brain injury and implications for speech
language pathology.
AB - This article provides an overview of the pharmacological management of traumatic
brain injury (TBI). A basic introduction to key pharmacokinetic and
pharmacodynamic principles is used to guide the reader. The goals of the
pharmacological management of TBI are explained starting with mild TBI. The main
medications used for each medical condition are described with a primary emphasis
of effects that may interfere with the role of speech-language pathology (SLP).
Some medications may interfere with cognitive, motor, and neuromuscular
functions, and others may cause ototoxicity. A basic overview of the
pharmacological management of moderate to severe TBI is included because the SLP
practitioner may encounter patients with TBI during the recovery phase. The
importance of assessment of swallowing evaluations is discussed because the oral
route of administration of medications is preferred once the patient is stable.
PMID- 25116214
TI - Management of athletes with postconcussion syndrome.
AB - Rehabilitation for athletes with postconcussion syndrome requires emphasis on
both cognitive and physical rest with a gradual return to activity and sports. As
the athlete becomes more active, the rehabilitation and sport professional should
pay close attention to symptoms of concussion, like headache, dizziness, nausea,
and difficulty concentrating. The Zurich Consensus Statement on Concussion in
Sport provides a systematic approach to increasing the intensity of physical
activity while attending to postconcussion symptoms. During the incident that led
to a concussion, the injured athlete may have incurred injuries to the vestibular
and balance system, which are not directly related to concussion. These
conditions are best addressed by professionals with specific training in
vestibular rehabilitation, most commonly physical therapists. Benign paroxysmal
positional vertigo is a condition in which otoconia particles in the inner ear
dislodge into the semicircular canals, resulting in severe vertigo and imbalance.
This condition frequently resolves with a few sessions with a vestibular
therapist and a home exercise program. In conditions like gaze instability,
motion sensitivity, impaired postural control, and cervicogenic dizziness,
improvement is more gradual and requires longer follow-up with a physical
therapist. In all of these conditions, it is important to consider that the
patient with postconcussion syndrome will likely recover more slowly than others
and should be monitored for symptoms of postconcussion syndrome throughout
intervention.
PMID- 25116215
TI - A model of prevention of sports concussion in adults.
AB - This article discusses the definitions of prevention and presents a model that
addresses multidimensional aspects of sports concussion prevention from the
perspectives of epidemiology, education, environmental modification, enforcement,
and evaluation. Epidemiology is helpful in identifying the incidence of
concussion and the interventions most likely to reduce its occurrence. Education
ensures that accurate information on concussion is communicated to stakeholders.
Modifications in the physical and sociocultural environments may lessen the
potential for injury and reduce the risk of concussion. Enforcement of
legislation standards can be effective in concussion prevention, especially at
the preinjury and injury phases. The evaluation dimension assesses the
effectiveness of prevention programs and guides future program development. This
five-E model explains concussion prevention as a recursive loop process. Each
dimension is closely associated in the prevention of sports concussion.
PMID- 25116216
TI - Clinical assessment of motor speech disorders in adults with concussion.
AB - This article reviews the occurrence of motor speech disorders of dysarthria and
apraxia of speech following closed head injury and other traumatic brain injuries
in adults as they apply to sport concussion and related trauma. Athletic sideline
and speech-language pathology screenings are considered. Procedures for clinical
assessment and diagnosis of motor speech disorder, most particularly dysarthria,
are discussed with special reference to closed head injury. Included are the
evaluation components of cranial nerve and speech mechanism examination,
nonspeech musculature examination, perceptual and instrumental assessment
procedures, quasi-standardized testing for dysarthria, and the determination of
restrictions of participation in everyday life activities. The resultant output
of such an evaluation is described in depth. Future directions for clinical
research on motor speech disorders following sports concussion are also briefly
considered.
PMID- 25116217
TI - Future of traumatic brain injury in adults.
AB - The previous articles in this compendium reviewed the past, present, and future
status of the diagnosis, prognosis, treatment, and prevention of mild traumatic
brain injury in the adult population. This article will discuss the issue of when
an individual should initiate the return-to-play (or class or work) protocol. The
clinical criterion to initiate the return-to-play protocol consists of
neuropsychological performance that returns to baseline and is stable, with no
reported symptoms. Recent functional magnetic resonance imaging (fMRI) studies
raise serious questions about these clinical criteria. fMRI results in
individuals with concussion are different from those of normal controls. Does
this difference represent cortical reorganization and/or cortical dysfunction? If
the imaging results reflect neuroplastic reorganization, then the initiation of
the return-to-play protocol is acceptable. However, if the imaging differences
indicate cortical dysfunction, then initiation of the return-to-play protocol
would not be advised. This article will describe the problem, the data available
to address this problem, and future research needs.
PMID- 25116219
TI - Bioimpedance in 7-year-old children: validation by dual X-ray absorptiometry -
part 2: assessment of segmental composition.
AB - AIM: Segmental body composition in children was assessed using the bioimpedance
analyzer (BIA) TANITA BC-418 and compared with dual-energy X-ray absorptiometry
(DXA) values. METHODS: A cross-sectional validation study in which 7-year-old
children from the Spanish subsample of the EU Childhood Obesity Project were
assessed through anthropometry, BIA and DXA. Main outcome measures were fat and
lean masses of the trunk, left arm and left leg (in kg) assessed through BIA
direct outputs (BIAoutputs) and DXA. Predictive equations for the composition of
each segment were derived from raw impedance and anthropometric measurements;
results obtained from these predictive equations (BIAregressions) were also
compared to DXA. RESULTS: One hundred seventy-one (84 boys) 7-year-old children
were studied. BIAoutputs and DXA results showed small differences for leg lean
mass (6.5%) and high differences for trunk fat and trunk lean masses (>30%).
BIAregressions results showed differences of about 20% for trunk fat mass, 1.5%
for trunk lean mass and 3.7% for leg lean mass compared to DXA. CONCLUSIONS:
Segmental body composition measures predicted by internal algorithms of the
TANITA BC-418 were not valid for clinical or epidemiological use, except for leg
lean mass. The assessment of segmental composition was improved using our own
predictive equations combining segmental-specific anthropometric measurements
with segmental impedances.
PMID- 25116218
TI - Comparison of the long-term effects on rabbit bone defects between Tetrabone and
beta-tricalcium phosphate granules implantation.
AB - Tetrabone is a newly developed granular artificial bone. The 1-mm Tetrabone has a
four-legged structure. In this study, the long-term effect of implanting
Tetrabone or beta-TCP granules in rabbit femoral cylindrical defects was
evaluated. The rabbits were euthanized at 4, 13, and 26 weeks after implantation.
Micro-CT was conducted to evaluate the residual material volume and the non
osseous tissue volume. New bone tissue areas were measured by histological
analysis. Micro-CT imaging showed that the residual material volume in the beta
TCP group had decreased significantly at 4 weeks after implantation (P < 0.05)
and that the beta-TCP granules had nearly disappeared at 26 weeks after
implantation. In the Tetrabone group, it did not significantly change until 13
weeks after implantation; it then continued to decrease slightly until 26 weeks
after implantation. The non-osseous volume increased in the beta-TCP group,
whereas that of the Tetrabone group decreased (P < 0.05). Histological
examination showed that the new bone areas were significantly greater in the
Tetrabone group than in the beta-TCP group at 13 and 26 weeks. In conclusion,
resorption of beta-TCP granules occurs before sufficient bone formation, thereby
allowing non-osseous tissue invasion. Tetrabone resorption progressed slowly
while the new bone tissues were formed, thus allowing better healing. Tetrabone
showed better osteoconductivity, whereas the beta-TCP granules lost their
function over a long duration. These results may be caused by the differences in
the absorption rate of the granules, intergranular pore structure, and
crystallinity of each granule.
PMID- 25116220
TI - Discovering mechanistic insights by application of tandem ultrafast
multidimensional NMR techniques.
AB - Ultrafast multidimensional NMR acquisition techniques have shown promising
capabilities in studies of dynamic systems in real time. The method's
characteristics have permitted the focus to be on the mechanistic details of
organic reactions. The tandem UF-TOCSY/HMBC sequence applied here combines both
homonuclear and heteronuclear details and therefore provides complete information
about the evolution of a dynamic reaction in real time. The methodology will be
applied to find an explanation of the low reactivity of alicyclic ketones such as
cyclohexanone in reactions with triflic anhydride and aliphatic nitriles, which
leads to bicyclic pyrimidines.
PMID- 25116222
TI - GP is allowed to practise again after affair with patient.
PMID- 25116221
TI - Mercury isotope study of sources and exposure pathways of methylmercury in
estuarine food webs in the Northeastern U.S.
AB - We measured mercury (Hg) isotope ratios in sediments and various estuarine
organisms (green crab, blue mussel, killifish, eider) to investigate
methylmercury (MMHg) sources and exposure pathways in five Northeast coast (U.S.)
estuaries. The mass independent Hg isotopic compositions (MIF; Delta(199)Hg) of
the sediments were linearly correlated with the sediment 1/Hg concentrations
(Delta(199)Hg: r(2) = 0.77, p < 0.05), but the mass dependent isotope
compositions (MDF; delta(202)Hg) were not (r(2) = 0.26, p = 0.16), reflecting
inputs of anthropogenic Hg sources with varying delta(202)Hg. The estuarine
organisms all display positive Delta(199)Hg values (0.21 to 0.98 0/00) indicating
that MMHg is photodegraded to varying degrees (5-12%) prior to entry into the
food web. The delta(202)Hg and Delta(199)Hg values of most organisms can be
explained by a mixture of MMHg and inorganic Hg from sediments. At one
contaminated site mussels have anomalously high delta(202)Hg, indicating exposure
to a second pool of MMHg, compared to sediment, crabs and fish. Eiders have
similar Delta(199)Hg as killifish but much higher delta(202)Hg, suggesting that
there is an internal fractionation of delta(202)Hg in birds. Our study shows that
Hg isotopes can be used to identify multiple anthropogenic inorganic Hg and MMHg
sources and determine the degree of photodegradation of MMHg in estuarine food
webs.
PMID- 25116223
TI - Using an unconventional perfusion pattern in ear replantation-arterialization of
the venous system.
AB - Ear amputation is a devastating injury characterized by a conspicuous deformity
that is not easily concealed and can result in tremendous psychological trauma in
addition to the physical insult. While numerous different approaches have been
proposed, microvascular replantation is widely considered to deliver the best
esthetic outcome. In this article, the authors report a case in which an
unconventional perfusion pattern (i.e., arterialization of the venous system) was
chosen, as intraoperative anatomic conditions precluded conventional vascular
reconstruction. A 25-year-old male patient sustained a human bite resulting in
subtotal amputation of his left ear. In the setting of an adequate arterial donor
vessel, that is, branch of the posterior auricular artery, and a single suitable
recipient vein (0.4 mm), the decision was made to perform an end-to-end arterio
venous anastomosis without the use of vein grafts. Medicinal leeches were applied
postoperatively to provide for venous drainage. The ear survived and the patient
was discharged after 14 days. To the best of our knowledge, this is first case of
a subtotal ear amputation that was successfully replanted by arterialization of
the venous system without the use of vein grafts and with preservation of the
superficial temporal vessels.
PMID- 25116224
TI - Potential protection of vitamin C against liver-lesioned mice.
AB - Pathologically, liver injury can result from sustained trauma to hepatocytes,
including acute damage. Thus, attenuation of hepatocellular lesion may help
improve liver functions. The purpose of this study was to explore the potential
advantages of vitamin C (VC) intake on acutely intralesional liver in carbon
tetrachloride (CCl4)-exposed mice. Here our data showed that VC supplementation
contributed to ameliorated vital signs of CCl4-lesioned mice, resulting in dose
dependent reduction of hepatomegaly. VC lowered the levels of liver functional
enzymes including alanine aminotransferase (ALT) and glutamic-oxaloacetic
transaminase (AST) in serum, while concentration of lactic acid concentration in
blood plasma was decreased. VC-administered CCl4-lesioned mice manifested
increased activities of superoxide dismutase (SOD) and glutathione peroxidase
(GSH-PX), while the malondialdehyde (MDA) content was reduced in liver tissue.
Moreover, VC consumption attenuated hepatotoxic injuries of CCl4-lesioned mice,
in which the number of TNF-alpha positive cells was dose-dependently reduced.
Furthermore, intrahepatic expression of TRL-4 mRNA, a vital inflammation
regulator, was down-regulated in VC-administered mice. Overall, we conclude that
VC has the potentiality of anti-hepatotoxicity that is capable of ameliorating
liver functions, speculating that therapeutic mechanism relates to normalizing
metabolism and blocking inflammatory stress in the liver.
PMID- 25116225
TI - Effect of Kuwanon G isolated from the root bark of Morus alba on ovalbumin
induced allergic response in a mouse model of asthma.
AB - The root bark of Morus alba L. (Mori Cortex Radicis; MCR) is traditionally used
in Korean medicine for upper respiratory diseases. In this study, we investigated
the antiasthmatic effect of kuwanon G isolated from MCR on ovalbumin (OVA)
induced allergic asthma in mice. Kuwanon G (1 and 10 mg/kg) was administered
orally in mice once a day for 7 days during OVA airway challenge. We measured the
levels of OVA-specific IgE and Th2 cytokines (IL-4, IL-5, and IL-13) in the sera
or bronchoalveolar lavage (BAL) fluids and also counted the immune cells in BAL
fluids. Histopathological changes in the lung tissues were analyzed. Kuwanon G
significantly decreased the levels of OVA-specific IgE and IL-4, IL-5, and IL-13
in the sera and BAL fluids of asthma mice. Kuwanon G reduced the numbers of
inflammatory cells in the BAL fluids of asthma mice. Furthermore, the
pathological feature of lungs including infiltration of inflammatory cells,
thickened epithelium of bronchioles, mucus, and collagen accumulation was
inhibited by kuwanon G. These results indicate that kuwanon G prevents the
pathological progression of allergic asthma through the inhibition of lung
destruction by inflammation and immune stimulation.
PMID- 25116226
TI - Multivertebral tubercular spondylodiscitis with abscesses in acute lymphoblastic
leukemia.
PMID- 25116227
TI - Summary health statistics for u.s. Adults: national health interview survey,
2003.
AB - Objectives-This report presents health statistics from the 2003 National Health
Interview Survey for the civilian noninstitutionalized adult population,
classified by sex, age, race and Hispanic origin, education, income, poverty
status, health insurance coverage, marital status, place of residence, and region
of residence for chronic condition prevalence, health status, functional
limitations, health care access and utilization, health behaviors, and human
immunodeficiency virus testing. Percentages and percent distributions are
presented in both age-adjusted and unadjusted versions. Source of Data-The NHIS
is a household, multistage probability sample survey conducted annually by
interviewers of the U.S. Census Bureau for the Centers for Disease Control and
Prevention's National Center for Health Statistics. In 2003, data were collected
for 30,852 adults for the Sample Adult questionnaire. The conditional response
rate was 84.5%, and the final response rate was 74.2%. The health information for
adults in this report was obtained from one randomly selected adult per family.
Highlights-In 2003, 62% of adults 18 years of age or over reported excellent or
very good health. Fifty-nine percent of adults never participated in any type of
vigorous leisure-time physical activity, and 14% of adults did not have a usual
place of health care. Eleven percent of adults had been told by a doctor or
health professional that they had heart disease, and 21% had been told on two or
more visits that they had hypertension. Twenty-two percent of all adults were
current smokers, and 22% were former smokers. Based on estimates of body mass
index, 36% of adults were overweight and 23% were obese.
PMID- 25116228
TI - Secondary malignant neoplasms among children, adolescents, and young adults with
osteosarcoma.
AB - BACKGROUND: As patients with osteosarcoma become long-term survivors, increasing
attention has turned to the burden of late effects. The goal of the current study
was to describe the incidence, characteristics, and outcomes of secondary
malignant neoplasms (SMNs) in this population. METHODS: Patients aged birth to 40
years at time of primary diagnosis with osteosarcoma and reported to the
Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2010
were eligible for inclusion in the cohort. Competing risks methods were used to
estimate the cumulative incidence of SMNs and potential risk factors for
developing an SMN. Standardized incidence ratios (SIR) and overall survival after
an SMN were estimated. RESULTS: The SEER database included 3379 patients who were
diagnosed with osteosarcoma as their first malignancy. Of these, 89 patients were
diagnosed with an SMN. The cumulative incidence of any SMN was 2.1% (95%
confidence interval [95% CI], 1.6%-2.7%) at 10 years, 4.0% (95% CI, 3.1%-5.1%) at
20 years, and 7.4% (95% CI, 5.6%-9.5%) at 30 years. The median time from the
primary diagnosis to an SMN diagnosis was 6.0 years. The SIR for SMNs for
survivors of osteosarcoma compared with the general population was 1.6 (95% CI,
1.0-2.5) for patients diagnosed with osteosarcoma from 1973 through 1985 and 4.7
(95% CI, 3.3-6.4) for patients diagnosed with osteosarcoma from 1986 through
2010, with a 34-fold increased risk of leukemia in this most recent era. The
overall survival rate at 5 years for patients with SMNs after a diagnosis of
osteosarcoma was 44.5%. CONCLUSIONS: Survivors of osteosarcoma are at an
increased risk of developing SMNs compared with the baseline population, with an
increased risk noted in patients treated in the more recent era.
PMID- 25116229
TI - Serum hepcidin measured by immunochemical and mass-spectrometric methods and
their correlation with iron status indicators in healthy children aged 0.5-3 y.
AB - BACKGROUND: The diagnostic use of hepcidin is limited by the absence of
standardization and lack of age-specific reference ranges in children in
particular. The aim of this study was to determine reference ranges of serum
hepcidin in healthy children aged 0.5-3 y using mass spectometry (MS) and a
commercial immunochemical (IC) assay, and to investigate its association with
other indicators of iron status and inflammation. METHODS: We included 400
healthy children aged 0.5-3 y. We constructed reference ranges for MS-hepcidin
and IC-hepcidin concentrations using the median, P2.5, and P97.5 in a normative
population of 219 children with no anemia, no infection and/or inflammation, and
no iron deficiency. RESULTS: Median concentrations (P2.5-P97.5) of MS-hepcidin
and IC-hepcidin were 3.6 nmol/l (0.6-13.9 nmol/l) and 7.9 nmol/l (1.9-28.6
nmol/l), respectively. We found a good correlation between both methods. However,
MS-hepcidin was consistently lower than IC-hepcidin. Hepcidin correlated with
ferritin and C-reactive protein. CONCLUSION: We provide reference ranges for
hepcidin for an MS and commercial IC method. Absolute values between assays
differed significantly, but hepcidin concentrations obtained by MS and IC methods
correlate with each other, and both correlate with ferritin and CRP.
PMID- 25116230
TI - Cardiovascular risk markers until 12 mo of age in infants fed a formula
supplemented with bovine milk fat globule membranes.
AB - BACKGROUND: Some of the health advantages of breast-fed as compared to formula
fed infants have been suggested to be due to metabolic programming effects
resulting from early nutrition. METHODS: In a prospective double-blinded
randomized trial, 160 infants <2 mo of age were randomized to experimental
formula (EF) with added milk fat globule membrane (MFGM) or standard formula (SF)
until 6 mo of age. A breast-fed reference (BFR) group consisted of 80 infants.
Measurements were made at inclusion and at 4, 6, and 12 mo of age. RESULTS:
During the intervention, the EF group had higher total serum cholesterol
concentration than the SF group, reaching the level of the BFR group. The EF
group had a low-density lipoprotein to high-density lipoprotein ratio not
significantly different from the SF group but lower than the BFR group.
CONCLUSION: Supplementation of infant formula with MFGM modified the fat
composition of the formula and narrowed the gap between breast-fed and formula
fed infants with regard to serum lipid status at 12 mo.
PMID- 25116231
TI - Fibrous Tendon Hypertrophy after Gastrocnemius Recession: A Case Report.
AB - Surgical complications after gastrocnemius recession have been rare in published
studies. We report a case of symptomatic fibrous tendon hypertrophy requiring
revision surgery. Additionally, we have provided a review of the published data
on the complications related to this procedure.
PMID- 25116232
TI - A biomechanical comparison of internal fixation techniques for ankle arthrodesis.
AB - The purpose of the present study was to compare the primary bending stiffness
characteristics of 5 different ankle arthrodesis fixation techniques: 3
compression screws, an anterior locking plate, a lateral locking plate, an
anterior locking plate with a compression screw, and a lateral locking plate with
a compression screw. A total of 25 full-scale anatomic models consisting of
fourth-generation composite tibiae and tali were tested using an Instron 4505
Universal Testing System. We hypothesized that the use of a compression screw
with a locking plate would add considerable stiffness to the fixation construct
compared with the use of a locking plate alone. The data have shown that an
anterior or lateral plate with a compression screw provides significantly greater
stiffness than both a plate and 3 compression screws used individually. No
significant difference was seen between the anterior plate with a compression
screw and the lateral plate with a compression screw. No significant differences
were found among the use of an anterior plate, a lateral plate, or 3 compression
screws. We have concluded that when using a locking plate in an anterior or
lateral configuration, the addition of a compression screw will considerably
increase the primary bending stiffness of ankle arthrodesis.
PMID- 25116233
TI - Tibiocalcaneal Fusion for Charcot Ankle With Severe Talar Body Loss: Case Report
and a Review of the Surgical Literature.
AB - Severe bone loss resulting from talar body necrosis in the Charcot ankle can be
challenging to treat. In particular, the Charcot ankle will demonstrate
progressive instability and deformity, causing protrusion of the medial or
lateral malleolus, which will mostly lead to skin ulcers or osteomyelitis and, in
some cases, will ultimately require transtibial amputation. Problems such as bone
fragility, poor compliance with load-bearing restrictions, susceptibility to
infection, and circulatory disorders cause difficulties in the surgical treatment
of the Charcot ankle. We believe that tibiocalcaneal fusion is a reliable method
to obtain satisfactory outcomes in these difficult cases. However, no study has
reported on the use of a locking plate for tibiocalcaneal fusion. Therefore, we
report on tibiocalcaneal fusion using a locking plate in 3 patients with Charcot
ankle and severe talar body loss. All patients achieved bony union with a
plantigrade foot and without any skin complications. We have concluded that a
locking plate provides rigid fixation and easier insertion of additional screws,
when necessary.
PMID- 25116234
TI - Women in limbo: life course consequences of infertility in a Nigerian community.
AB - Infertility is a devastating problem around the world, particularly in the high
fertility context of sub-Saharan Africa. Regardless of its medical origins,
infertility causes African women personal grief and economic deprivation.This
research was conducted among the Ijo who are organized into exogamous patrilineal
descent groups. Women who marry into a patrilineage are perceived as bearers of
sons who will eventually take their place in the lineage's genealogy. Women only
figure in the lineage structure as mothers.In addition to extensive ethnographic
research in this community, the paper is based on a combination of surveys of 246
women and interviews of 25 fertile and 25 infertile women.Women who have never
given birth were characterized as "useless". Some managed to accumulate wealth or
attained education but most feared a marginal old age. Respect was given to women
who have had even one child, even if that child died. The biological process of
gestation confers an adult status on women allowing them to undergo initiation
and to function as mature individuals. In the life course the most prominent
periods of suffering are the transition from the stages of ereso (girl) to erera
(mature woman), and in the period of old age.
PMID- 25116235
TI - Exceptionally strong and robust millimeter-scale graphene-alumina composite
membranes.
AB - Graphene has attracted attention as a potential strengthening material and
functional component in suspended membranes as utilized in micro and nanosystems.
Development of a practical and scalable fabrication process is a necessary step
to allow the exceptional material properties of graphene to be fully exploited in
composite structures. Using standard and scalable microfabrication processes, we
fabricated free-standing chemical vapor deposition monolayer graphene-reinforced
Al2O3 composite membranes, 0.5 mm in diameter, that are strong and robust. Bulge
tests revealed that the graphene reinforcement increased the membrane fracture
strength by a factor of at least three and maximum sustainable strain from 0.28%
to at least 0.69%. We show that the graphene-reinforced membranes are even
tolerant to significant cracking without loss of membrane integrity. The graphene
composite membranes' freestanding area of ~ 200 000 MUm(2) is almost a thousand
times larger than suspended graphene membranes reported elsewhere. The presented
graphene composite membranes may be seen as representing an interesting new class
of durable composite materials warranting further study and having potential for
broad applicability in a variety of fields.
PMID- 25116236
TI - Unraveling the enhanced photocatalytic activity and phototoxicity of ZnO/metal
hybrid nanostructures from generation of reactive oxygen species and charge
carriers.
AB - An effective way for promoting photocatalytic activity of a semiconductor is
deposition of noble metal nanoparticles (NPs) onto it. In this paper, we
deposited Ag and Pd onto ZnO NPs to form ZnO/Ag and ZnO/Pd hybrid nanostructures.
It was found that both Ag and Pd nanocomponents can greatly enhance the
photocatalytic activity and phototoxicity of ZnO toward human skin cells. Using
electron spin resonance spectroscopy with spin trapping and spin labeling
techniques, we observed that either deposition of Ag or Pd resulted in a
significant increase in photogenerated electrons and holes and production of
reactive oxygen species including hydroxyl radicals, superoxide, and singlet
oxygen. We compared the enhancing effects of Ag and Pd and found that Pd is more
effective than Ag in promoting the generation of hydroxyl radicals and holes and
the photocatalytic activity of ZnO. Conversely, Ag is more effective than Pd in
enhancing electron transfer and the generation of superoxide and singlet oxygen.
The mechanism underlying the differences in the effects of Ag and Pd may be
related to differences in Fermi levels for Ag and Pd and band bending accompanied
by effects on Schottky barriers. The results of these studies provide information
valuable for designing hybrid nanomaterials having photocatalytic and
photobiological activities useful for applications such as water purification and
formulation of antibacterial products.
PMID- 25116237
TI - Identification of bromophenol thiohydantoin as an inhibitor of DisA, a c-di-AMP
synthase, from a 1000 compound library, using the coralyne assay.
AB - c-di-AMP is an important bacterial second messenger found in Gram-positive and
mycobacteria. c-di-AMP regulates myriads of processes in bacteria as well as
immune response in higher organisms so interest in small molecules that would
attenuate the activity of c-di-AMP metabolism enzymes is high. Herein, we report
the first small molecule inhibitor of a c-di-AMP synthase, DisA, using a coralyne
based assay.
PMID- 25116238
TI - Statistically quantified measurement of an Alzheimer's marker by surface-enhanced
Raman scattering.
AB - Fibrillar forms of the Amyloid-beta (Abeta) protein have been implicated in the
early stages of Alzheimer's disease (AD), however there are no standardised
assays for soluble Abeta oligomer biomarkers that provide the best indication of
the disease progression [1,2]. As a step towards a fast and label-free method for
testing different AD biomarkers, we have combined laser nano-textured substrates
with a SERS mapping technique and validated it using soluble Abeta-40 oligomers
[3-5]. The nano-textured SERS substrates provide fast (&5 min), label-free
spectra associated with soluble Abeta-40 oligomers down to a concentration of 10
nM. Statistical analysis of the spectral intensities mapped over the substrate
surface shows a quantitative correlation with the oligomer concentration.
Schematics of experiments: SERS mapping of Abeta-40 (left figure: measured SERS
intensity overlayed with an SEM image of ripples) was carried out on the laser
nano-textured (ripple) surface of sapphire and statistical analysis of the SERS
intensity was carried out for qualitative (a high SERS intensity at low
probability) and quantitative (a moderate SERS intenisty at the highest
probability) measures. Quantitative statistical analysis of SERS mapping data can
be performed off line for cross correlations with other known SERS signatures.
PMID- 25116240
TI - [Special topics in pediatric orthopedics: options and limits of growth guidance].
AB - BACKGROUND: A main task of pediatric orthopedics is the treatment of legs of
different lengths or misshapen legs. Whereas for adult patients complicated and
invasive operative interventions are necessary, the growth potential of the
epiphysial plate can be utilized in childhood and adolescence to correct leg
length differences and leg axis deformities. THERAPY: Epiphysiodesis leads to a
guidance of growth via a temporary or permanent and partial or complete blockade
of the epiphysial plate depending on the indications. This method is principally
a less invasive procedure with few complications. CONCLUSION: Careful
preoperative assessment of the indications and planning, precise operative
technique and attentive postoperative control investigations are absolutely
essential for successful treatment.
PMID- 25116241
TI - [Congenital dysplasia and dislocation of the hip: proven and new procedures in
diagnostics and therapy].
AB - BACKGROUND: As developmental dysplasia of the hip (DDH) is the most common
congenital muskuloskeletal anomaly, it seems necessary to give an update on the
normal growth, pathoanatomy, diagnostic and therapeutic procedures. OBJECTIVES:
Which investigations or procedures have withstood the test of time? What are new
therapeutic strategies and considerations? What are the problems? METHODS: Review
of the current literature on DDH supplemented by several years experience in the
treatment of this condition by the authors. RESULTS: We have still a long way to
achieve the goal of agreement on universal standardization of assessment and
treatment methods based on age and staging regarding DDH, as in the Ponseti
treatment procedure for clubfoot. CONCLUSION: Our experiences, as well as the
literature suggest the use of Graf's nomenclature for classification of DDH in
the first year of life. If dynamic ultrasound (US) shows at least a partial
relocation of a decentered hip in the first 6 weeks of life, splinting in human
position is advocated. The treatment of a Graf type IV hip joint is very
difficult and often need surgery. The established surgical procedures in the
literature are still up to date. Radiological follow-up of the affected as well
as the unaffected side until the end of the growth phase is mandatory due to the
risk of residual dysplasia.
PMID- 25116242
TI - [Epiphyseolysis of the femoral head: new aspects of diagnostics and therapy].
AB - BACKGROUND: Slipped capital femoral epiphysis (SCFE) is the most common hip
disease in adolescents and is always surgically treated with the aim to avoid
further slippage and to reduce the risk of degenerative arthritis at young age.
OBJECTIVES: A summary of the etiology, pathogenesis, clinical features,
radiographic imaging and current therapy concepts is given. MATERIAL AND METHODS:
A selective review of the literature was performed. RESULTS: With an increasing
body mass index in adolescents the incidence of SCFE also increases. The
diagnostic routine is comprised of a clinical examination with the evaluation of
Drehmann's sign and a radiographic evaluation including anterior-posterior aspect
and frog's legs view. In situ stabilization with a single screw is the standard
treatment for the most prevalent mild or moderate stable slippages. In cases of
acute slippage a gentle reduction maneuver may be attempted. Hardware removal
must not be performed before epiphyseal closure. Common bilateral but not
simultaneous occurrence of the disease requires prophylactic pinning of the
unaffected side by default, at least in central Europe. Various surgical
treatment options exist to reduce the femoroacetabular impingement caused by the
slippage. CONCLUSIONS: Current treatment algorithms result in satisfactory long
term outcomes. If the risk of developing degenerative arthritis after SCFE may be
reduced even more with modern arthroscopic or open surgical procedures to restore
the anatomic pre-slip conditions has to be confirmed through further long-term
studies. The implementation of programs to prevent obesity in adolescents may
also reduce the incidence of SCFE.
PMID- 25116243
TI - [Aseptic osteonecrosis in children and adolescents].
AB - BACKGROUND: Aseptic osteonecrosis (AO) in children and adolescents has been
described in all parts of the skeleton. The disease is presumed to be caused by
local blood circulation disorders, the reasons for which are multifactorial and
occur more often in times of stronger growth intensity. DISEASE SEQUELAE: The
disease leads to bone catabolism which can affect the epiphyses, metaphyses,
apophyses, carpal and tarsal bones of the hands and feet. The more stretched the
form alteration of the bone at the end of the diseases is, the earlier arthritic
alterations occur due to the incongruence of the corresponding joint partner. If
a growth plate is affected, a growth disorder can be the result. DIAGNOSTICS AND
THERAPY: The diagnostics and therapeutic measures are oriented to the site and
extent of the disease and the age of the child. For early forms of AO magnetic
resonance imaging (MRI) is the imaging method of choice. In recent years the
medicinal therapy of AO has been described as an additional option. The disease
lasts at least several months up to years and more commonly affects boys than
girls with the exception of necrosis of the foot tarsals. CONCLUSION: The early
diagnosis and immediate initiation of adequate therapy which must take the age
and stage of the disease into consideration, can reduce a possible joint
destruction. Prostaglandin therapy, as an off label use, leads to a reduction of
pain and improvement in mobility.
PMID- 25116239
TI - Whole-genome sequencing of individuals from a founder population identifies
candidate genes for asthma.
AB - Asthma is a complex genetic disease caused by a combination of genetic and
environmental risk factors. We sought to test classes of genetic variants largely
missed by genome-wide association studies (GWAS), including copy number variants
(CNVs) and low-frequency variants, by performing whole-genome sequencing (WGS) on
16 individuals from asthma-enriched and asthma-depleted families. The samples
were obtained from an extended 13-generation Hutterite pedigree with reduced
genetic heterogeneity due to a small founding gene pool and reduced environmental
heterogeneity as a result of a communal lifestyle. We sequenced each individual
to an average depth of 13-fold, generated a comprehensive catalog of genetic
variants, and tested the most severe mutations for association with asthma. We
identified and validated 1960 CNVs, 19 nonsense or splice-site single nucleotide
variants (SNVs), and 18 insertions or deletions that were out of frame. As follow
up, we performed targeted sequencing of 16 genes in 837 cases and 540 controls of
Puerto Rican ancestry and found that controls carry a significantly higher burden
of mutations in IL27RA (2.0% of controls; 0.23% of cases; nominal p = 0.004;
Bonferroni p = 0.21). We also genotyped 593 CNVs in 1199 Hutterite individuals.
We identified a nominally significant association (p = 0.03; Odds ratio (OR) =
3.13) between a 6 kbp deletion in an intron of NEDD4L and increased risk of
asthma. We genotyped this deletion in an additional 4787 non-Hutterite
individuals (nominal p = 0.056; OR = 1.69). NEDD4L is expressed in bronchial
epithelial cells, and conditional knockout of this gene in the lung in mice leads
to severe inflammation and mucus accumulation. Our study represents one of the
early instances of applying WGS to complex disease with a large environmental
component and demonstrates how WGS can identify risk variants, including CNVs and
low-frequency variants, largely untested in GWAS.
PMID- 25116244
TI - [Chronic knee pain in children and adolescents: review of anatomical and overload
related knee pain].
AB - BACKGROUND: Knee pain in children and adolescents is a common reason for
presentation in pediatric orthopedic consultation. The causes are manifold and
require a thorough patient history, detailed physical examination and extensive
diagnostics. DIAGNOSTICS: Chronic knee pain in children and adolescents is a
diagnosis by exclusion. An extensive patient history including training habits,
pain localization and clinical examination provide indications vital for the
diagnosis. Overuse is often the trigger. In dynamic investigations consideration
should be given to muscle imbalance. Imaging techniques have a high sensitivity
and specificity only in combination with the anamnesis and clinical findings.
THERAPY: With pain therapy, targeted physiotherapy, a break in active sport or
training modifications, the prognosis is good for overload syndromes. An
operative therapy after unsuccessful conservative therapy is necessary in only a
few cases. Among the anatomy-related types of knee pain primary popliteal cysts
mostly require no therapy and for plica syndrome arthroscopic resection should
only be necessary if conservative treatment is unsuccessful. Operative therapy is
necessary for symptomatic discoid meniscus.
PMID- 25116245
TI - [Osteogenesis imperfecta].
AB - BACKGROUND: Osteogenesis imperfecta (OI) is the most common genetic disease of
bone and is characterized by fragile bones and growth disorders of varying
severity. Most cases of OI are inherited autosomal dominant and caused by a
mutation in the collagen type I gene. DIAGNOSTICS: Indications for OI are bone
fragility, stunted growth, scoliosis, skull deformities, blue sclera, loss of
hearing, dentinogenesis imperfecta and increased laxity of ligaments and skin. In
most cases it is possible to make a clinical diagnosis but a skin biopsy or
genetic testing can be useful; however, negative results for these tests do not
exclude OI. THERAPY: Therapy must be carried out in a multidisciplinary team and
includes conservative (e.g. physiotherapy, rehabilitation programs and orthopedic
aids), operative (e.g. intramedullary stabilization procedures) and
pharmaceutical (e.g. biphosphonates and growth hormones) procedures. PROGNOSIS:
The prognosis depends on the type of OI and ranges from normal life expectations
for type 1 patients up to up to perinatal mortality for type II patients.
PMID- 25116246
TI - [Differences between short stem prostheses].
AB - The short stem designs currently available are significantly different and can be
differentiated into neck containing, partial containing and neck resection
designs. In this article, the differences in the design features are presented.
These include the differences in the technique of implantation, the significant
differences in the reproducibility of the given anatomy of the patient and also
concerning their osteologic competence.
PMID- 25116247
TI - [Thromboprophylaxis and platelet aggregation inhibitors in spinal surgery:
perioperative management].
AB - BACKGROUND: The perioperative use of anticoagulants (AC) and platelet aggregation
inhibitors (PAI) in the field of spinal surgery suggests an increased rate of
epidural bleeding. However, evidence is lacking and these medications are most
often indispensable in the prevention of thromboembolic complications.
Comprehensive recommendations for the correct use of AC and PAI are lacking.
OBJECTIVE: The aim of this study was an analysis of the current situation with
regards to the use of AC and PAI in spinal surgery and development of new
recommendations. MATERIAL AND METHODS: Two independent surveys on the
perioperative use of AC and PAI were obtained from centers for spinal surgery in
Germany. The study obtained information on the perioperative use of AC and PAI,
risk assessment of thromboembolic and hemorrhagic events as well as on the type
and extent of the substance groups used. RESULTS: Almost the entire patient
collective (98%) received perioperative low molecular weight heparin. In 64% the
medical prophylaxis was started before surgery and in 36% after surgery. The
period of prophylaxis was determined arbitrarily. Approximately 40% of
interviewees employed paravertebral infiltration and 19% injected into the
epidural space in patients on PAI medication. Open spinal canal surgery was
performed in 30% of PAI medicated patients and closed spinal canal surgery was
executed in 40%. The risk assessment of PAI differed significantly between
aspirin and receptor blocker medication as well as dual administration of PAI.
DISCUSSION: The use of AC and PAI in spinal surgery in Germany is very
heterogeneous and large deviations from the guidelines frequently occurred.
Therefore, there is a strong need for further studies to accurately assess the
perioperative use of AC and PAI and to formulate precise recommendations.
PMID- 25116248
TI - Expectancy effects during response selection modulate attentional selection and
inhibitory control networks.
AB - Choosing the correct response from a subset of alternatives is a fundamental
problem and particularly demanding where conflicting response tendencies are
evident. One phenomenon in this context is the congruency sequence-(Gratton
effect), for which different theoretical explanations have been put forward. A
critical aspect that differs between these explanations is the expectancy of what
will happen in forthcoming trials. In the current study we examine the relevance
of expectancy for sequence congruency effects and related neurophysiological
processes using a flanker task in which we manipulate the probability that the
n+1 trial presents the same stimulus-response mapping than the n trial. We ask
what cognitive subprocesses involved in response selection may be modulated by
expectancy effects. To distinguish different subprocesses probably modulated by
expectancy effects we use event-related potentials (ERPs) in combination with
source localization techniques. The data show that cognitive subprocesses
modulated by expectancy depend on the nature of expected transitions between
succeeding trials. Expectancy effects only affected trial transitions within the
same category (i.e., 'compatible-compatible' and 'incompatible-incompatible'),
but not between compatibility categories (i.e., 'compatible-incompatible' and
'incompatible-compatible'). On compatible trial transitions attentional selection
processes operating via the precuneus mediated expectancy effects, while on
incompatible trial transitions inhibitory processes were modulated that were
mediated via the medial and middle frontal gyrus, the orbitofrontal cortex, the
insular and the parahippocampal gyrus. Conflict monitoring processes per se were
not modulated by expectancy effects. The data shows that there are different
subprocesses underlying the influence of expectancy on sequence effects during
response selection.
PMID- 25116250
TI - Genetic variability in the human cannabinoid receptor 1 is associated with
resting state EEG theta power in humans.
AB - It has long been postulated that exogenous cannabinoids have a profound effect on
human cognitive functioning. These cannabinoid effects are thought to depend, at
least in parts, on alterations of phase-locking of local field potential neuronal
firing. The latter can be measured as activity in the theta frequency band (4
7Hz) by electroencephalogram. Theta oscillations are supposed to serve as a
mechanism in neural representations of behaviorally relevant information.
However, it remains unknown whether variability in endogenous cannabinoid
activity is involved in theta rhythms and therefore, may serve as an individual
differences index of human cognitive functioning. To clarify this issue, we
recorded resting state EEG activity in 164 healthy human subjects and extracted
EEG power across frequency bands (delta, theta, alpha, and beta). To assess
variability in the endocannabinoid system, two genetic polymorphisms (rs1049353,
rs2180619) within the cannabinoid receptor 1 (CB1) were determined in all
participants. As expected, we observed significant effects of rs1049353 on EEG
power in the theta band at frontal, central and parietal electrode regions.
Crucially, these effects were specific for the theta band, with no effects on
activity in the other frequency bands. Rs2180619 showed no significant
associations with theta power after Bonferroni correction. Taken together, we
provide novel evidence in humans showing that genetic variability in the
cannabinoid receptor 1 is associated with resting state EEG power in the theta
frequency band. This extends prior findings of exogenous cannabinoid effects on
theta power to the endogenous cannabinoid system.
PMID- 25116249
TI - Deletion of KCC3 in parvalbumin neurons leads to locomotor deficit in a
conditional mouse model of peripheral neuropathy associated with agenesis of the
corpus callosum.
AB - Hereditary motor and sensory neuropathy associated with agenesis of the corpus
callosum (HMSN/ACC or ACCPN) is an autosomal recessive disease caused by the
disruption of the SLC12A6 gene, which encodes the K-Cl cotransporter-3 (KCC3). A
ubiquitous deletion of KCC3 in mice leads to severe locomotor deficits similar to
ACCPN patients. However, the underlying pathological mechanism leading to the
disease remains unclear. Even though a recent study suggests that the neuropathic
features of ACCPN are mostly due to neuronal loss of KCC3, the specific cell type
responsible for the disease is still unknown. Here we established four tissue
specific KCC3 knockout mouse lines to explore the cell population origin of
ACCPN. Our results showed that the loss of KCC3 in parvalbumin-positive neurons
led to significant locomotor deficit, suggesting a crucial role of these neurons
in the development of the locomotor deficit. Interestingly, mice in which KCC3
deletion was driven by the neuron-specific enolase (NSE) did not develop any
phenotype. Furthermore, we demonstrated that nociceptive neurons targeted with
Nav1.8-driven CRE and Schwann cells targeted with a desert hedgehog-driven CRE
were not involved in the development of ACCPN. Together, these results establish
that the parvalbumin-positive neuronal population is an important player in the
pathogenic development of ACCPN.
PMID- 25116251
TI - Neuropeptide AF induces anxiety-like and antidepressant-like behavior in mice.
AB - Little is known about the action of neuropeptide AF (NPAF) on anxiety and
depression. Only our previous study provides evidence that NPAF induces anxiety
like behavior in rats. Therefore, the aim of the present study was to investigate
the action of NPAF on depression-like behavior and the underlying
neurotransmissions in mice. In order to determine whether there are species
differences between rats and mice, we have investigated the action of NPAF on
anxiety-like behavior in mice as well. A modified forced swimming test (mFST) and
an elevated plus maze test (EPMT) were used to investigate the depression and
anxiety-related behaviors, respectively. Mice were treated with NPAF 30min prior
to the tests. In the mFST, the animals were pretreated with a non-selective
muscarinic acetylcholine receptor antagonist, atropine, a non-selective 5-HT2
serotonergic receptor antagonist, cyproheptadine, a mixed 5-HT1/5-HT2
serotonergic receptor antagonist, methysergide, a D2/D3/D4 dopamine receptor
antagonist, haloperidol, a alpha1/alpha2beta-adrenergic receptor antagonist,
prazosin or a non-selective beta-adrenergic receptor antagonist, propranolol
30min before the NPAF administration. In the mFST, NPAF decreased the immobility
time and increased the climbing and swimming times. This action was reversed
completely by methysergide and partially by atropine, whereas cyproheptadine,
haloperidol, prazosin and propranolol were ineffective. In the EPMT, NPAF
decreased the time spent in the arms (open/open+closed). Our results demonstrate
that NPAF induces anti-depressant-like behavior in mice, which is mediated, at
least in part, through 5HT2-serotonergic and muscarinic cholinergic
neurotransmissions. In addition, the NPAF-induced anxiety is species-independent,
since it develops also in mice.
PMID- 25116252
TI - Gait analysis and the cumulative gait index (CGI): Translational tools to assess
impairments exhibited by rats with olivocerebellar ataxia.
AB - Deviations from 'normal' locomotion exhibited by humans and laboratory animals
may be determined using automated systems that capture both temporal and spatial
gait parameters. Although many measures generated by these systems are unrelated
and independent, some may be related and dependent, representing redundant
assessments of function. To investigate this possibility, a treadmill-based
system was used to capture gait parameters from normal and ataxic rats, and a
multivariate analysis was conducted to determine deviations from normal. Rats
were trained on the treadmill at two speeds, and gait parameters were generated
prior to and following lesions of the olivocerebellar pathway. Control (non
lesioned) animals exhibited stable hindlimb gait parameters across assessments at
each speed. Lesioned animals exhibited alterations in multiple hindlimb gait
parameters, characterized by significant increases in stride frequency, braking
duration, stance width, step angle, and paw angle and decreases in stride,
stance, swing and propulsion durations, stride length and paw area. A principal
component analysis of initial hindlimb measures indicated three uncorrelated
factors mediating performance, termed Rhythmicity, Thrust and Contact. Deviation
in the performance of each animal from the group mean was determined for each
factor and values summed to yield the cumulative gait index (CGI), a single value
reflecting variation within the group. The CGI for lesioned animals increased 2.3
fold relative to unlesioned animals. This study characterizes gait alterations in
laboratory rats rendered ataxic by destruction of the climbing fiber pathway
innervating Purkinje cells and demonstrates that a single index can be used to
describe overall gait impairments.
PMID- 25116253
TI - Periaqueductal gray MU and kappa opioid receptors determine behavioral selection
from maternal to predatory behavior in lactating rats.
AB - Every mother must optimize her time between caring for her young and her
subsistence. The rostro lateral portion of the periaqueductal grey (rlPAG) is a
critical site that modulates the switch between maternal and predatory behavior.
Opioids play multiple roles in both maternal behavior and this switching process.
The present study used a pharmacological approach to evaluate the functional role
of rlPAG MU and kappa opioid receptors in behavioral selection. Rat dams were
implanted with a guide cannula in the rlPAG and divided into three experiments in
which we tested the role of opioid agonists (Experiment 1), the influence of MU
and kappa opioid receptor blockade in the presence of morphine (Experiment 2),
and the influence of MU and kappa opioid receptor blockade (Experiment 3). After
behavioral test, in Experiment 4, we evaluated rlPAG MU and kappa receptor
activation in all Experiments 1-3. The results showed that massive opioidergic
activation induced by morphine in the rlPAG inhibited maternal behavior without
interfering with predatory hunting. No behavioral changes and no receptor
activation were promoted by the specific agonist alone. However, kappa receptor
blockade increased hunting behavior and increased the level of MU receptor
activation in the rlPAG. Thus, endogenous opioidergic tone might be modulated by
a functional interaction between opioid receptor subtypes. Such a compensatory
receptor interaction appears to be relevant for behavioral selection among
motivated behaviors. These findings indicate a role for multiple opioid receptor
interactions in the modulation of behavioral selection between maternal and
predatory behaviors in the PAG.
PMID- 25116254
TI - Re: 'The impact of chronic kidney disease on postoperative outcome following
colorectal cancer surgery'.
PMID- 25116255
TI - Synthesis and Antimicrobial Activity of 5-(morpholinosulfonyl)isatin Derivatives
Incorporating a Thiazole Moiety.
AB - This article describes the synthesis of novel 5-(morpholinosulfonyl)isatin
derivatives having biologically active thiazole moiety were synthesized via 2
synthetic routes. The first route involved interaction of 5-(morpholino-sulfonyl)
isatin with aminothiazole derivatives to give the Schiff's base derivatives (2,
3). The second route involved preparation of thiosemicarbazones (4-7) by
treatment of 5-(morpholino- sulfonyl) isatin with thiosemicarbazides followed by
cycloalkylation of the products with halogenated compounds to give the thiazole
derivatives (8-19). Most of the synthesized compounds were screened against Gram
(+), Gram (-) bacterial and fungi. The best gram positive activity was displayed
by compounds 1, 13, 14, 15, 16 and 18 and the best gram negative bacteria was
showed by compounds 1, 12, 13, 15, and 19, whereas compounds 1, 12, 13, 15, and
19 exhibited the best antifungal activity.
PMID- 25116256
TI - Synthesis and characterization of some substituted 3, 4-dihydronaphthalene
derivatives through different enaminones as potent cytotoxic agents.
AB - A new series of novel substituted 3,4-dihydronaphthalene incorporated to
benzo[h]quinoline, benzo[g]indazole, thiazolidin-4-one, pyrazolo[3,4-d]thiazol
and thiazolo[4,5-b]pyridine ring systems were synthesized and evaluated for their
cytotoxicity against selected human cancer cell lines. Some of the tested
compounds exhibited promising carcinoma growth inhibition. The detailed
synthesis, spectroscopic data and biological activities of the tested compounds
were reported.
PMID- 25116257
TI - Comparison of paper- and web-based dietary records: a pilot study.
AB - BACKGROUND/AIMS: Paper-based dietary records (Paper-DR) can be replaced by web
based dietary records (Web-DR) in both epidemiological studies and clinical
practice to reduce the time and logistic burden. We aimed to compare Paper-DR and
Web-DR. METHODS: We compared the matching of different food items (n = 1,103)
from Paper-DR and Web-DR for energy and 48 nutrients among 16 pregnant
volunteers, with DR for the same individuals matched for the same 4 days. Paper
DR were coded into the web-based version (referred to as Paper-Web-DR)
independently by the same research dietitian. The Wilcoxon signed-rank test
comparing mean rank differences, Spearman's rho to measure associations and Bland
Altman limits of agreement to evaluate the level of agreement between the two
dietary methods across the range of parameters were used. Volunteers also
completed an evaluation questionnaire regarding the user acceptability of Paper
DR and Web-DR. RESULTS: A high correlation between Paper-DR and Web-DR was noted.
There were statistically insignificant differences among 45 nutrients, except for
free sugars (p < 0.001), alpha-linolenic acid (p = 0.041), folate (p = 0.036) and
pantothenic acid (p = 0.023). Volunteers found the Paper-DR equally time
consuming as the Web-DR. The majority of the volunteers (75%) preferred the Web
DR. CONCLUSIONS: Paper-DR and Web-DR were comparable across a range of
nutritional parameters, with a few exceptions. The Web-DR was more convenient for
the majority and has substantial logistic and cost advantages.
PMID- 25116258
TI - Gene expression profiling analysis of locus coeruleus in idiopathic Parkinson's
disease by bioinformatics.
AB - This study aimed to explore the underlying molecular mechanisms of idiopathic
Parkinson's disease (IPD) by bioinformatics analysis. Gene expression profile
GSE34516 was downloaded from the Gene Expression Omnibus. Eight locus coeruleus
post-mortem tissue samples derived from four IPD patients and four neurological
healthy controls were used to identify the differentially expressed genes (DEGs)
by paired t test. Based on the DEGs, principal components were analyzed. The Gene
Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway analysis
of the genome microarray data were then performed. Finally, protein-protein
interaction (PPI) network of the DEGs was constructed. Total 261 DEGs including
195 up-regulated and 66 down-regulated DEGs were identified. Intracellular
protein transport and RNA splicing via transesterification reactions were
selected as the most two significantly enriched functions. Mismatch repair, N
glycan biosynthesis, spliceosome and nucleotide excision repair were the
significantly enriched pathways. In the PPI network, CTSS, CD53, IGSF6, PTPRC and
LAPTM5 were the hub nodes. Intracellular protein transport and RNA splicing via
transesterification reactions were closely associated with IPD. The DEGs, such as
CX3CR1, SLC5A7, CD53 and PTPRC may be the potential targets for IPD diagnosis and
treatment.
PMID- 25116259
TI - Taste impairment in Miller Fisher syndrome.
PMID- 25116260
TI - Familiar Mediterranean fever and multiple sclerosis: an unreported association in
the Italian population?
PMID- 25116262
TI - PRIMO: Precise radiofrequency inference from multiple observations.
AB - PURPOSE: This paper presents Precise Radiofrequency Inference from Multiple
Observations (PRIMO), a comprehensive reconstruction framework for calibrating
MRI systems with parallel transmit and parallel receive radiofrequency
capabilities. THEORY AND METHODS: To date, the vast majority of radiofrequency
(RF) calibration methods have considered transmit and receive calibration
separately, without acknowledging that transmit field calibration sequences
measure sufficient data for receive calibration. PRIMO provides a method of
extracting both transmit and receive fields from transmit calibration data
without presuming knowledge of either. The method is tested for accuracy through
simulation, comparison to a gold standard dataset, and is demonstrated on in-vivo
data acquired at 3T. RESULTS: PRIMO is shown to produce RF fields faithful to the
gold standard with errors of less than 3% in realistic noise conditions. The in
vivo reconstructions demonstrate the method's ability to produce high quality
transmit and receive maps, with an 8 transmit/8 receive channel system being
fully calibrated in three dimensions in approximately 2 minutes. CONCLUSION:
PRIMO provides a unified framework for estimating all transmit and receive fields
in a single calibration step. This is becoming increasingly relevant in an era of
MRI systems with highly parallel RF architectures.
PMID- 25116264
TI - Oxidation of reduced sulfur species: carbon disulfide.
AB - A detailed chemical kinetic model for oxidation of CS2 has been developed, on the
basis of ab initio calculations for key reactions, including CS2 + O2 and CS +
O2, and data from literature. The mechanism has been evaluated against
experimental results from static reactors, flow reactors, and shock tubes. The
CS2 + O2 reaction forms OCS + SO, with the lowest energy path involving crossing
from the triplet to the singlet surface. For CS + O2, which yields OCS + O, we
found a high barrier to reaction, causing this step to be important only at
elevated temperatures. The model predicts low temperature ignition delays and
explosion limits accurately, whereas at higher temperatures it appears to
overpredict both the induction time for CS2 oxidation and the formation rate of
[O] upon ignition. The predictive capability of the model depends on the accuracy
of the rate constant for the initiation step CS2 + O2, which is difficult to
calculate due to the intersystem crossing, and the branching fraction for CS2 +
O, which is measured only at low temperatures. The governing reaction mechanisms
are outlined on the basis of calculations with the kinetic model.
PMID- 25116261
TI - The tumor-educated-macrophage increase of malignancy of human pancreatic cancer
is prevented by zoledronic acid.
AB - We previously defined macrophages harvested from the peritoneal cavity of nude
mice with subcutaneous human pancreatic tumors as "tumor-educated-macrophages"
(Edu) and macrophages harvested from mice without tumors as "naive-macrophages"
(Naive), and demonstrated that Edu-macrophages promoted tumor growth and
metastasis. In this study, Edu- and Naive-macrophages were compared for their
ability to enhance pancreatic cancer malignancy at the cellular level in vitro
and in vivo. The inhibitory efficacy of Zoledronic acid (ZA) on Edu-macrophage
enhanced metastasis was also determined. XPA1 human pancreatic cancer cells in
Gelfoam co-cultured with Edu-macrophages proliferated to a greater extent
compared to XPA1 cells cultured with Naive-macrophages (P = 0.014). XPA1 cells
exposed to conditioned medium harvested from Edu culture significantly increased
proliferation (P = 0.016) and had more migration stimulation capability (P<0.001)
compared to cultured cancer cells treated with the conditioned medium from Naive.
The mitotic index of the XPA1 cells, expressing GFP in the nucleus and RFP in the
cytoplasm, significantly increased in vivo in the presence of Edu- compared to
Naive-macrophages (P = 0.001). Zoledronic acid (ZA) killed both Edu and Naive in
vitro. Edu promoted tumor growth and metastasis in an orthotopic mouse model of
the XPA1 human pancreatic cancer cell line. ZA reduced primary tumor growth (P =
0.006) and prevented metastasis (P = 0.025) promoted by Edu-macrophages. These
results indicate that ZA inhibits enhanced primary tumor growth and metastasis of
human pancreatic cancer induced by Edu-macrophages.
PMID- 25116266
TI - First total synthesis of antihypertensive natural products S-(+)-XJP and R-(-)
XJP.
AB - The first asymmetric total synthesis of antihypertensive natural products S-(+)
XJP and R-(-)-XJP has been achieved in 8 steps starting from commercially
available 6-bromo-2-hydroxy-3-methoxybenzaldehyde. Key steps included
intramolecular Heck reaction and oxidative ozonolysis reaction with the retention
of stereochemistry. A latent functionality strategy was implemented to circumvent
the racemization in this endeavor. The protocol described here provided a fast
and easily accessible synthetic method to obtain optically pure isochroman-4-one
derivatives. Furthermore, the in vivo antihypertensive effects of (+/-)-XJP, S
(+)-XJP and R-(-)-XJP were investigated on spontaneously hypertensive rats. The
obtained results could provide valuable information to identify a promising lead
for further chemical modification research.
PMID- 25116265
TI - Frequent words do not break continuous flash suppression differently from
infrequent or nonexistent words: implications for semantic processing of words in
the absence of awareness.
AB - Continuous flash suppression (CFS) has been used as a paradigm to probe the
extent to which word stimuli are processed in the absence of awareness. In the
two experiments reported here, no evidence is obtained that word stimuli are
processed up to the semantic level when suppressed through CFS. In Experiment 1,
word stimuli did not break suppression faster than their pseudo-word variants nor
was suppression time modulated by word frequency. Experiment 2 replicated these
findings, but more critically showed that differential effects can be obtained
with this paradigm using a simpler stimulus. In addition, pixel density of the
stimuli did prove to be related to suppression time in both experiments,
indicating that the paradigm is sensitive to differences in detectability. A
third and final experiment replicated the well-known face inversion effect using
the same set-up as Experiments 1 and 2, thereby demonstrating that the employed
methodology can capture more high-level effects as well. These results are
discussed in the context of previous evidence on unconscious semantic processing
and two potential explanations are advanced. Specifically, it is argued that CFS
might act at a level too low in the visual system for high-level effects to be
observed or that the widely used breaking CFS paradigm is merely ill-suited to
capture effects in the context of words.
PMID- 25116267
TI - Electronic structure study of Ce1-xAxO2 (A = Zr & Hf) nanoparticles: NEXAFS and
EXAFS investigations.
AB - Single phase nanoparticles (NPs) of CeO2, Ce0.5Zr0.5O2, Ce0.5Hf0.5O2 and
Ce0.5Hf0.25Zr0.25O2 were successfully synthesized by co-precipitation method at
constant pH and temperature. The X-ray diffraction results revealed that the
additive atoms did not segregate to form secondary phases but led to grain size
variation in the NPs. The 10 Dq values in the near edge X-ray absorption fine
structure (NEXAFS) spectra at the O K-edge did not vary in the same way as the
average grain size was changed for the doped CeO2 NPs. The deconvolution of Ce M5
edge and detailed analysis of O K pre-edge peak have shown the higher
Ce(+3)/(Ce(+3) + Ce(+4)) ratio in the Zr- and Hf-doped samples. The local atomic
structure around the Ce, Zr and Hf atoms was investigated using extended X-ray
absorption fine structure (EXAFS) spectroscopy at Ce K-edge, Zr K-edge and Hf L3
edge, respectively, and the EXAFS data were fitted with the theoretical
calculations. The 4f occupancy, Ce(+3)/(Ce(+3) + Ce(+4)) ratio of Ce ions,
coordination number of Ce and Ce-Ce/Ce-O bond distances were sensitive to the
additive atoms but not explicitly changed according to the grain size variation
in the NPs.
PMID- 25116268
TI - Tranexamic acid use and postoperative outcomes in patients undergoing total hip
or knee arthroplasty in the United States: retrospective analysis of
effectiveness and safety.
AB - OBJECTIVE: To determine the effectiveness and safety of perioperative tranexamic
acid use in patients undergoing total hip or knee arthroplasty in the United
States. DESIGN: Retrospective cohort study; multilevel multivariable logistic
regression models measured the association between tranexamic acid use in the
perioperative period and outcomes. SETTING: 510 US hospitals from the claims
based Premier Perspective database for 2006-12. PARTICIPANTS: 872,416 patients
who had total hip or knee arthroplasty. INTERVENTION: Perioperative intravenous
tranexamic acid use by dose categories (none, <= 1000 mg, 2000 mg, and >= 3000
mg). MAIN OUTCOME MEASURES: Allogeneic or autologous transfusion, thromboembolic
complications (pulmonary embolism, deep venous thrombosis), acute renal failure,
and combined complications (thromboembolic complications, acute renal failure,
cerebrovascular events, myocardial infarction, in-hospital mortality). RESULTS:
While comparable regarding average age and comorbidity index, patients receiving
tranexamic acid (versus those who did not) showed lower rates of allogeneic or
autologous transfusion (7.7% v 20.1%), thromboembolic complications (0.6% v
0.8%), acute renal failure (1.2% v 1.6%), and combined complications (1.9% v
2.6%); all P<0.01. In the multilevel models, tranexamic acid dose categories
(versus no tranexamic acid use) were associated with significantly (P<0.001)
decreased odds for allogeneic or autologous blood transfusions (odds ratio 0.31
to 0.38 by dose category) and no significantly increased risk for complications:
thromboembolic complications (odds ratio 0.85 to 1.02), acute renal failure (0.70
to 1.11), and combined complications (0.75 to 0.98). CONCLUSIONS: Tranexamic acid
was effective in reducing the need for blood transfusions while not increasing
the risk of complications, including thromboembolic events and renal failure.
Thus our data provide incremental evidence of the potential effectiveness and
safety of tranexamic acid in patients requiring orthopedic surgery.
PMID- 25116269
TI - Metastatic rhabdoid meningioma with BRAF V600E mutation and good response to
personalized therapy: case report and review of the literature.
AB - Rhabdoid meningioma is an aggressive phenotype of meningioma, associated with a
poor prognosis. We present a very rare case of high-grade meningioma with
rhabdoid features that eventually expressed in a coma state. Comprehensive
genomic profiling using a Next Generation Sequencing (NGS) assay revealed three
genomic alterations: activating BRAF mutation (V600E), loss of CDKN2A/2B, and APC
I1307K. After treatment with BRAF inhibitor (dabrafenib), the child's clinical
condition improved progressively. After seven months, an MEK inhibitor was added
(trametinib).
PMID- 25116270
TI - Summary health statistics for u.s. Adults: national health interview survey,
2004.
AB - Objectives-This report presents health statistics from the 2004 National Health
Interview Survey for the civilian noninstitutionalized adult population,
classified by sex, age, race and Hispanic origin, education, family income,
poverty status, health insurance coverage, marital status, place of residence,
and region of residence for chronic condition prevalence, health status,
functional limitations, health care access and utilization, health behaviors, and
human immunodeficiency virus testing. Percentages and percent distributions are
presented in both age-adjusted and unadjusted versions. Source of Data-The NHIS
is a household, multistage probability sample survey conducted annually by
interviewers of the U.S. Census Bureau for the Centers for Disease Control and
Prevention's National Center for Health Statistics. In 2004, data were collected
for 31,326 adults for the Sample Adult questionnaire. The conditional response
rate was 83.8%, and the final response rate was 72.5%. The health information for
adults in this report was obtained from one randomly selected adult per family.
In very rare instances where the sample adult was not able to respond for him or
herself, a proxy was allowed. Highlights-In 2004, 62% of adults 18 years of age
or over reported excellent or very good health. Sixty-two percent of adults never
participated in any type of vigorous leisure-time physical activity, and 15% of
adults did not have a usual place of health care. Twelve percent of adults had
been told by a doctor or health professional that they had heart disease, and 22%
had been told on two or more visits that they had hypertension. Twenty-one
percent of all adults were current smokers, and 21% were former smokers. Based on
estimates of body mass index, 35% of adults were overweight and 24% were obese.
PMID- 25116272
TI - Quantification of the steric influence of alkylphosphine-sulfonate ligands on
polymerization, leading to high-molecular-weight copolymers of ethylene and polar
monomers.
AB - A series of palladium/alkylphosphine-sulfonate catalysts were synthesized and
examined in the homopolymerization of ethylene and the copolymerization of
ethylene and polar monomers. Catalysts with alkylphosphine-sulfonate ligands
containing sterically demanding alkyl substituents afforded (co)polymers whose
molecular weight was increased by up to 2 orders of magnitude relative to
polymers obtained from previously reported catalyst systems. The polymer
molecular weight was found to be closely correlated to the Sterimol B5 parameter
of the alkyl substituents in the alkylphosphine-sulfonate ligands. Thus, the use
of bulky alkylphosphine-sulfonate ligands represents an effective and versatile
method to prepare high-molecular-weight copolymers of ethylene and various polar
monomers, which are difficult to obtain by previously reported methods.
PMID- 25116271
TI - IgA kappa/IgA lambda heavy/light chain assessment in the management of patients
with IgA myeloma.
AB - BACKGROUND: Accurate quantification of immunoglobulin A (IgA) monoclonal
immunoglobulins by serum protein electrophoresis (SPEP) can be difficult and can
impact the assessment of response among patients with multiple myeloma (MM).
Therefore, there is a need to identify new assays that better reflect disease
burden and response to treatment, and correlate with patient outcome. IgA
Hevylite (HLC) measures IgA kappa and IgA lambda separately and provides precise
quantitative measurements of the monoclonal IgA expression and polyclonal-isotype
matched suppression. In the current study, the authors assessed the usefulness of
these assays in the diagnosis of IgA MM and sought to comment on the prognostic
value of the assays. METHODS: A study of 157 patients with IgA MM for whom
diagnostic samples were available was performed. HLC measurements were performed
on a nephelometer and the results were compared with those of electrophoresis.
RESULTS: All presentation sera (100 IgA kappa specimens and 57 IgA lambda
specimens) were found to have abnormal IgA HLC ratios (IgA kappa median ratio:
336.2 [range, 8.2-7353] and IgA lambda ratio: 0.011 [range, 0.0003-0.45]). In
comparison, SPEP bands were quantifiable in only 105 of 157 samples (67%)
(median, 28.5 g/L [range, 2.2 g/L-98 g/L]). Of the total of 157 patients, 12
patients (8%) presented with oligosecretory myeloma (<10 g/L; including 4
patients with nonquantifiable SPEP bands). HLC uniquely allows for the
measurement of isotype paired suppression, which was found to be associated with
shortened overall survival in the current study. CONCLUSIONS: In the current
study, IgA HLC ratios were found to be abnormal in all patients and the assay was
able to produce quantifiable results in more MM sera than either SPEP or total
IgA, potentially representing a solution to the issue of comigration and
oligosecretory MM. These preliminary data require confirmation in larger
prospective trials to validate the usefulness of IgA HLC.
PMID- 25116273
TI - Modeling and simulation of count data.
AB - Count data, or number of events per time interval, are discrete data arising from
repeated time to event observations. Their mean count, or piecewise constant
event rate, can be evaluated by discrete probability distributions from the
Poisson model family. Clinical trial data characterization often involves
population count analysis. This tutorial presents the basics and diagnostics of
count modeling and simulation in the context of pharmacometrics. Consideration is
given to overdispersion, underdispersion, autocorrelation, and inhomogeneity.
PMID- 25116275
TI - The psychological impact of infertility and fertility treatment on the male
partner.
AB - OBJECTIVES: This paper reports the findings of two studies that examined factors
predicting infertility distress in male partners within couples with an
infertility diagnosis and where the couple was receiving fertility treatment.
DESIGN: A cross-sectional design was implemented using a questionnaire battery
(The questionnaire battery comprised an inventory of four different standardised
questionnaires compiled together into one booklet) compiled from earlier theory
building qualitative research conducted by the authors. METHODS: Infertility
related distress was examined in relation to a number of psychosocial variables
including relationship dynamics, self-esteem, current mental health and attitudes
towards idealised masculinity. The questionnaire battery was completed by 167 men
undergoing or consulting for fertility treatment. Participants were recruited
through Irish fertility clinics (Study 1, n = 111) and through an online survey
(Study 2, n = 55). RESULTS: Regression analyses identified four variables that
predicted variance in infertility distress in both studies: 'Attitude towards
idealised masculinity', 'Mental health', 'Relationship satisfaction' and 'Self
esteem'. This finding was found to be robust having controlled for age, time
since diagnosis, number of attempts at treatment and diagnostic category (male
factor, female factor or mixed factor infertility). ConclusiON: Recommendations
for fertility clinics and mental health professionals should be made in relation
to managing infertility distress and supporting couples during fertility
treatment.
PMID- 25116274
TI - Interaction Between Domperidone and Ketoconazole: Toward Prediction of Consequent
QTc Prolongation Using Purely In Vitro Information.
AB - We aimed to investigate the application of combined mechanistic pharmacokinetic
(PK) and pharmacodynamic (PD) modeling and simulation in predicting the
domperidone (DOM) triggered pseudo-electrocardiogram modification in the presence
of a CYP3A inhibitor, ketoconazole (KETO), using in vitro-in vivo extrapolation.
In vitro metabolic and inhibitory data were incorporated into physiologically
based pharmacokinetic (PBPK) models within Simcyp to simulate time course of
plasma DOM and KETO concentrations when administered alone or in combination with
KETO (DOM+KETO). Simulated DOM concentrations in plasma were used to predict
changes in gender-specific QTcF (Fridericia correction) intervals within the
Cardiac Safety Simulator platform taking into consideration DOM, KETO, and
DOM+KETO triggered inhibition of multiple ionic currents in population.
Combination of in vitro-in vivo extrapolation, PBPK, and systems pharmacology of
electric currents in the heart was able to predict the direction and magnitude of
PK and PD changes under coadministration of the two drugs although some
disparities were detected.
PMID- 25116276
TI - The effect of diabetes mellitus on costs and length of stay in patients with
peripheral arterial disease undergoing vascular surgery.
AB - OBJECTIVE: To determine the impact of diabetes mellitus (DM) and other
comorbidities on length of stay (LOS) and costs in patients with peripheral
arterial disease (PAD) admitted to a vascular surgical unit. METHODS: A
retrospective study was conducted between January 2011 and July 2012 at a
tertiary referral hospital in Sydney. Demographic, laboratory, and operative data
were obtained from the Australasian Vascular Audit database and hospital
diagnostic-related group (DRG) reports. Patients with confirmed PAD with or
without DM requiring hospital admission for a diagnosis of claudication, rest
pain, ulcer/gangrene, and infection that required lower limb surgical
intervention were included. Associations between LOS, surgical procedure, and DRG
were explored. RESULTS: Five hundred and sixty-eight admissions (492 patients)
were identified: 292 admissions with PAD and 276 admissions with PAD in
conjunction with DM (PADDM). Mean LOS for patients with PAD was 10 +/- 13.7 days
compared with 15 +/- 18.2 days for PADDM (p < .01; 95% confidence interval 2.7
8.0). LOS and costs were greatest in patients with PADDM undergoing major
amputation (37 +/- 13.7 days; US$42,236; p < .01). Analysis of variance indicated
that the best predictors of LOS were the presence of DM, bypass surgery,
amputation, chronic kidney disease (CKD) stage V, infection, and emergency
admission. Over 18 months, the estimated total inpatient costs associated with
lower limb intervention for PAD with and without DM amounted to US$7,598,597.
People with DM incurred greater inpatient costs, averaging US$1,912 more per
episode of admission and a total of US$528,029 over 18 months. CONCLUSION: The
impact of diabetes as a comorbid condition in patients with PAD is significant,
both clinically and economically. Factors that predict increased LOS in patients
with PAD are DM, bypass surgery, amputation, CKD stage V, infection, and
emergency admission.
PMID- 25116277
TI - Therapeutic effect of compression stockings versus no compression on isolated
superficial vein thrombosis of the legs: a randomized clinical trial.
AB - OBJECTIVE/BACKGROUND: Leg compression is considered basic treatment for
superficial vein thrombosis (SVT), although scientific proof for its efficacy is
lacking. The aim of the study was to evaluate the therapeutic effect of
compression stockings on isolated SVT of the legs. METHODS: This was a single
center randomized controlled trial. Eighty patients with isolated SVT of the legs
were instructed to wear compression stockings (23-32 mmHg) (CG) or no compression
(NCG) for 3 weeks. All patients received low molecular weight heparin (LMWH) at
prophylactic dosage. Non-steroidal anti-inflammatory drugs (NSAIDs) were allowed.
The primary outcome variable was the reduction of pain as assessed by a visual
analog scale (VAS) and the Lowenberg test. Secondary outcomes were the
consumption of analgesics, thrombus length, skin erythema, D-dimer, and quality
of life (QoL). RESULTS: Seventy-three patients completed the study. Clinical
symptoms and QoL significantly improved from baseline to day 21 in both groups (p
< .001 for VAS, Lowenberg test, thrombus length, and erythema; p < .006 for QoL),
and consumption of analgesics and D-dimer significantly decreased (p < .001).
There was no significant difference between the groups for all tested variables.
At day 7, patients in the CG revealed a significantly faster thrombus regression
(p = .02). CONCLUSION: Adding compression stockings for 3 weeks to LMWH and
NSAIDs does not bring significant additional benefit in the treatment of isolated
SVT. When worn for 1 week, compression stockings stimulate significantly faster
thrombus regression.
PMID- 25116278
TI - Folic acid functionalized silver nanoparticles with sensitivity and selectivity
colorimetric and fluorescent detection for Hg2+ and efficient catalysis.
AB - In this research, folic acid functionalized silver nanoparticles (FA-AgNPs) were
selected as a colorimetric and a 'turn on' fluorescent sensor for detecting
Hg(2+). After being added into Hg(2+), AgNPs can emit stable fluorescence at 440
nm when the excitation wavelength is selected at 275 nm. The absorbance and
fluorescence of the FA-AgNPs could reflect the concentration of the Hg(2+) ions.
Thus, we developed a simple, sensitive analytical method to detect Hg(2+) based
on the colorimetric and fluorescence enhancement of FA-AgNPs. The sensor exhibits
two linear response ranges between absorbance and fluorescence intensity with
Hg(2+) concentration, respectively. Meanwhile, a detection limit of 1 nM is
estimated based on the linear relationship between responses with a concentration
of Hg(2+). The high specificity of Hg(2+) with FA-AgNPs interactions provided the
excellent selectivity towards detecting Hg(2+) over other metal ions (Pb(2+),
Mg(2+), Zn(2+), Ni(2+), Cu(2+), Co(2+), Ca(2+), Mn(2+), Fe(2+), Cd(2+), Ba(2+),
Cr(6+) and Cr(3+)). This will provide a simple, effective and multifunctional
colorimetric and fluorescent sensor for on-site and real-time Hg(2+) ion
detection. The proposed method can be applied to the analysis of trace Hg(2+) in
lake water. Additionally, the FA-AgNPs can be used as efficient catalyst for the
reduction of 4-nitrophenol and potassium hexacyanoferrate (III).
PMID- 25116279
TI - Benzothiazole derivatives augment glucose uptake in skeletal muscle cells and
stimulate insulin secretion from pancreatic beta-cells via AMPK activation.
AB - Adenosine monophosphate-activated protein kinase (AMPK) has been identified as
one of the major targets for antidiabetic drugs. This study describes two AMPK
activating agents 2-(benzo[d]thiazol-2-ylmethylthio)-6-ethoxybenzo[d]thiazole and
2-(propylthio)benzo[d]thiazol-6-ol, that increase the rate of glucose uptake in
L6 myotubes and also augment glucose-stimulated insulin secretion in INS-1E beta
cells and rat islets. We believe that such unique bi-functional compounds can be
further used for the development of a new class of antidiabetic drugs.
PMID- 25116280
TI - Recycling of carbon dioxide and acetate as lactic acid by the hydrogen-producing
bacterium Thermotoga neapolitana.
AB - The heterotrophic bacterium Thermotoga neapolitana produces hydrogen by
fermentation of sugars. Under capnophilic (carbon dioxide requiring) conditions,
the process is preferentially associated with the production of lactic acid,
which, as shown herein, is synthesized by reductive carboxylation of acetyl
coenzyme A. The enzymatic coupling is dependent on the carbon dioxide stimulated
activity of heterotetrameric pyruvate:ferredoxin oxidoreductase. Under the same
culture conditions, T. neapolitana also operates the unfavorable synthesis of
lactic acid from an exogenous acetate supply. This process, which requires carbon
dioxide (or carbonate) and an unknown electron donor, allows for the conversion
of carbon dioxide into added-value chemicals without biomass deconstruction.
PMID- 25116281
TI - Fouling-tolerant nanofibrous polymer membranes for water treatment.
AB - Nafion/polyvinylidene fluoride (PVDF) nanofibrous membranes with
electrostatically negative charges on the fiber surface were fabricated via
electrospinning with superior water permeability and antifouling behaviors in
comparison with the conventional microfiltration membranes. The fiber diameter
and the resultant pore size in the nanofibrous membranes were easily controlled
through tailoring the properties of the electrospinning solutions. The
electrospun Nafion/PVDF nanofibrous membranes revealed high porosities (>80%) and
high densities of sulfonate groups on the membrane surface, leading to
praiseworthy water permeability. Unexpectedly, the water permeability was
observed as proportional to the fiber diameter and pore size in the membrane. The
presence of sulfonate groups on the membrane improved the antifouling performance
against negatively charged oily foulants.
PMID- 25116292
TI - In vivo application of short-lag spatial coherence and harmonic spatial coherence
imaging in fetal ultrasound.
AB - Fetal scanning is one of the most common applications of ultrasound imaging and
serves as a source of vital information about maternal and fetal health.
Visualization of clinically relevant structures, however, can be severely
compromised in difficult-to-image patients due to poor resolution and the
presence of high levels of acoustical noise or clutter. We have developed novel
coherence-based beamforming methods called Short-Lag Spatial Coherence (SLSC)
imaging and Harmonic Spatial Coherence imaging (HSCI), and applied them to
suppress the effects of clutter in fetal imaging. This method is used to create
images of the spatial coherence of the backscattered ultrasound as opposed to
images of echo magnitude. We present the results of a patient study to assess the
benefits of coherence-based beamforming in the context of first trimester fetal
exams. Matched fundamental B-mode, SLSC, harmonic B-mode, and HSCI images were
generated using raw radio frequency data collected on 11 volunteers in the first
trimester of pregnancy. The images were compared for qualitative differences in
image texture and target conspicuity as well as using quantitative imaging
metrics such as signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and
contrast. SLSC and HSCI showed statistically significant improvements across all
imaging metrics compared with B-mode and harmonic B-mode, respectively. These
improvements were greatest for poor quality B-mode images where contrast of
anechoic targets was improved from 15 dB in fundamental B-mode to 27 dB in SLSC
and 17 dB in harmonic B-mode to 30 dB in HSCI. CNR improved from 1.4 to 2.5 in
the fundamental images and 1.4 to 3.1 in the harmonic case. These results exhibit
the potential of coherence-based beamforming to improve image quality and target
detectability, especially in high noise environments.
PMID- 25116293
TI - Two-dimensional ultrasound and ultrasound elastography imaging of trigger points
in women with myofascial pain syndrome treated by acupuncture and
electroacupuncture: a double-blinded randomized controlled pilot study.
AB - Chronic pain has been often associated with myofascial pain syndrome (MPS), which
is determined by myofascial trigger points (MTrP). New features have been tested
for MTrP diagnosis. The aim of this study was to evaluate two-dimensional
ultrasonography (2D US) and ultrasound elastography (UE) images and elastograms
of upper trapezius MTrP during electroacupuncture (EA) and acupuncture (AC)
treatment. 24 women participated, aged between 20 and 40 years (M +/- SD = 27.33
+/- 5.05) with a body mass index ranging from 18.03 to 27.59 kg/m2 (22.59 +/-
3.11), a regular menstrual cycle, at least one active MTrP at both right (RTPz)
and left trapezius (LTPz) and local or referred pain for up to six months.
Subjects were randomized into EA and AC treatment groups and the control sham AC
(SHAM) group. Intensity of pain was assessed by visual analogue scale; MTrP mean
area and strain ratio (SR) by 2D US and UE. A significant decrease of intensity
in general, RTPz, and LTPz pain was observed in the EA group (p = 0.027; p <
0.001; p = 0.005, respectively) and in general pain in the AC group (p < 0.001).
Decreased MTrP area in RTPz and LTPz were observed in AC (p < 0.001) and EA
groups (RTPz, p = 0.003; LTPz, p = 0.005). Post-treatment SR in RTPz and LTPz was
lower than pre-treatment in both treatment groups. 2D US and UE effectively
characterized MTrP and surrounding tissue, pointing to the possibility of
objective confirmation of subjective EA and AC treatment effects.
PMID- 25116295
TI - Effect of partial bladder outlet obstruction and reversal on rabbit bladder
physiology and biochemistry: duration of recovery period and severity of
function.
AB - OBJECTIVES: To use a rabbit model of partial bladder outlet obstruction (BOO) to
investigate the point at which obstructive bladder dysfunction becomes
irreversible. METHODS: Partial BOO was induced in New Zealand White rabbits. It
was then reversed and the rabbits were allowed to recover for 4, 8 or 12 weeks.
Both at the time of reversal and at the end of the study, the rabbits were
grouped according to bladder decompensation level (mild, intermediate or severe)
based on bladder mass (weight). RESULTS: A strong correlation was observed
between the production and distribution of collagen and the reduction of smooth
muscle contractile function. We found that only in the bladders that were
severely decompensated at the time of reversal did collagen levels not decrease.
CONCLUSION: The data show that recovery of function after reversal of partial BOO
is directly related primarily to collagen levels at the time of reversal.
PMID- 25116294
TI - Quality of dying in the ICU: is it worse for patients admitted from the hospital
ward compared to those admitted from the emergency department?
AB - OBJECTIVE: Although most intensive care unit (ICU) admissions originate in the
emergency department (ED), a substantial number of admissions arrive from
hospital wards. Patients transferred from the hospital ward often share clinical
characteristics with those admitted from the ED, but family expectations may
differ. An understanding of the impact of ICU admission source on family
perceptions of end-of-life care may help improve patient and family outcomes by
identifying those at risk for poor outcomes. DESIGN AND SETTING: This was a
cohort study of patients with chronic illness and acute respiratory failure
requiring mechanical ventilation who died after admission to an ICU in any of the
14 participating hospitals in the Seattle-Tacoma area between 2003 and 2008 (n =
1,500). MEASUREMENTS: Using regression models adjusted for hospital site and
patient-, nurse- and family-level characteristics, we examined associations
between ICU admission source (hospital ward vs. ED) and (1) family ratings of
satisfaction with ICU care; (2) family and nurse ratings of quality of dying; (3)
chart-based indicators of palliative care. MAIN RESULTS: Admission from the
hospital ward was associated with lower family ratings of quality of dying [beta
0.90, 95% confidence interval (CI) -1.54, -0.26, p = 0.006] and satisfaction
(total score beta -3.97, 95% CI -7.89, -0.05, p = 0.047; satisfaction with care
domain score beta -5.40, 95% CI -9.44, -1.36, p = 0.009). Nurses did not report
differences in quality of dying. Patients from hospital wards were less likely to
have family conferences [odds ratio (OR) 0.68, 95% CI 0.52, 0.88, p = 0.004] or
discussion of prognosis in the first 72 h after ICU admission (OR 0.72, 95% CI
0.56, 0.91, p = 0.007) but were more likely to receive spiritual care (OR 1.48,
95% CI 1.14, 1.93, p = 0.003) or have life support withdrawn (OR 1.38, 95% CI
1.04, 1.82, p = 0.025). CONCLUSION: Admission from the hospital ward is
associated with family perceptions of a lower quality of dying and less
satisfaction with ICU care. Differences in receipt of palliative care suggest
that family of patients from the hospital ward receive less communication. Nurse
ratings of quality of dying did not significantly differ by ICU admission source,
suggesting dissimilarities between family and nurse perspectives. This study
identifies a patient population at risk for poor quality palliative and end-of
life care. Future studies are needed to identify interventions to improve care
for patients who deteriorate on the wards following hospital admission.
PMID- 25116296
TI - Asparagus, a love story: healthier eating could be just a false memory away.
AB - In two experiments, involving 231 subjects, we planted the suggestion that
subjects loved to eat asparagus as children. Relative to controls, subjects
receiving the suggestion became more confident that they had loved asparagus the
first time they tried it. These new (false) beliefs had consequences for those
who formed them, including increased general liking of asparagus, greater desire
to eat asparagus in a restaurant setting, and a willingness to pay more for
asparagus in the grocery store. Ratings of photographs made after the suggestion
reveal that the altered nutritional choices may relate to the fact that the sight
of asparagus simply looks more appetizing and appealing. These results
demonstrate that adults can be led to believe that they had a positive food
related experience as children, and that these false beliefs can have healthy
consequences.
PMID- 25116297
TI - A role for spatial and nonspatial working memory processes in visual search.
AB - Searching a cluttered visual scene for a specific item of interest can take
several seconds to perform if the target item is difficult to discriminate from
surrounding items. Whether working memory processes are utilized to guide the
path of attentional selection during such searches remains under debate. Previous
studies have found evidence to support a role for spatial working memory in
inefficient search, but the role of nonspatial working memory remains unclear.
Here, we directly compared the role of spatial and nonspatial working memory for
both an efficient and inefficient search task. In Experiment 1, we used a dual
task paradigm to investigate the effect of performing visual search within the
retention interval of a spatial working memory task. Importantly, by
incorporating two working memory loads (low and high) we were able to make
comparisons between dual-task conditions, rather than between dual-task and
single-task conditions. This design allows any interference effects observed to
be attributed to changes in memory load, rather than to nonspecific effects
related to "dual-task" performance. We found that the efficiency of the
inefficient search task declined as spatial memory load increased, but that the
efficient search task remained efficient. These results suggest that spatial
memory plays an important role in inefficient but not efficient search. In
Experiment 2, participants performed the same visual search tasks within the
retention interval of visually matched spatial and verbal working memory tasks.
Critically, we found comparable dual-task interference between inefficient search
and both the spatial and nonspatial working memory tasks, indicating that
inefficient search recruits working memory processes common to both domains.
PMID- 25116298
TI - Does the central bottleneck encompass voluntary selection of hedonically based
choices?
AB - A large literature on multitasking bottlenecks suggests that people cannot
generally make decisions or select responses in two different tasks at the same
time. However, these tasks have all involved retrieving preinstructed responses,
rather than spontaneously choosing actions based on anticipated hedonic
consequences. To assess whether the same bottlenecks encompasses voluntary
choices, a gambling decision was utilized as the second of two tasks in a
psychological refractory period (PRP) design. Three decision-related factors were
identified that affected latency of responding in the gambling task. All proved
to be additive with stimulus-onset asynchrony (SOA) in dual-task blocks. The
results indicate that making a choice to try to optimize outcomes is subject to
the same processing bottleneck as the retrieval of preinstructed responses that
has been the mainstay of attention and performance research.
PMID- 25116299
TI - Stimulus-related inhibition of task set during task switching.
AB - Performance after a shifting of task is supported by the inhibition of the
executed task, as revealed by slower reaction times (RTs) on alternating compared
to nonalternating task sequences (ABA vs. CBA). In the present study we
investigated the role of stimulus processing in the establishment of task
inhibition during task switching, irrespective of the response selection process.
Comparing performance on AbA and CbA task sequences within a procedure in which
the b-task only involved stimulus encoding processes for later comparison but
response selection did not occur, we found slower RTs on AbA compared to CbA task
sequences. This revealed that inhibition of the executed task can be triggered at
the stimulus processing stage of the new task. In accordance, inhibition only
emerged when interference between tasks occurred at the stimulus level, due to
stimuli having features relevant for both the executed and the upcoming task.
PMID- 25116300
TI - Seeing the forest before the trees depends on individual field-dependency
characteristics.
AB - Numerous studies have demonstrated that the well-known global precedence effect,
characterized by a visual bias toward global information, is highly dependent on
stimulus characteristics (Kimchi, 1992). Despite the extensive global-local
literature, few studies have investigated how interindividual characteristics
could affect the global precedence effect. In this framework, we studied the
relationship between global-local visual biases and the Group Embedded Figure
Test (GEFT), a standardized measure of field dependency. Data from 34
participants were consistent with the idea that an individual's bias toward the
global level is linearly related to his or her degree of field dependence. Given
the important role that global-local visual skills play during visuospatial
tasks, these results have important implications for future research in this
area.
PMID- 25116301
TI - A comparison of bilateral versus unilateral target and distractor presentation in
the remote distractor paradigm.
AB - The remote distractor effect (RDE) is a robust finding of an increase in saccade
onset latencies (20-40 ms) when a distractor is presented simultaneously with a
target, compared to when a target is presented on its own (Walker, Deubel,
Schneider, & Findlay, 1997). Distractors presented at fixation produce the
largest RDE and the effect decreases as distractors are moved into the periphery.
Data from two experiments that contrast with these standard findings are
reported. Under bilateral target presentation, larger RDE magnitudes occurred for
peripheral than for central distractors, whereas under unilateral presentation,
the pattern reversed. The findings are discussed with reference to discrimination
processes, attentional factors and current models of oculomotor control. It is
suggested that in bilateral target presentation the competition between the
distractor and the target results in the programming of a saccade to the
distractor, as well as a saccade to the target. Time taken to cancel the saccade
to the distractor produces the increased saccade latency for peripheral
distractors in that condition.
PMID- 25116302
TI - Hindsight bias and the activation of counterfactual mind-sets.
AB - Previous research has shown that conditional counterfactuals are positively
related to the magnitude of creeping determinism. Unlike previous experiments
which show this increased hindsight bias to occur after exceptional antecedents,
we investigated another possible factor, namely a prior activation of a
counterfactual mind-set. We investigated our prediction using a hypothetical
scenario. Prior to reading the hindsight scenario some participants were asked to
solve a scrambled-sentence test including conditional counterfactual sentences.
Results of two experiments were consistent with our predictions: Participants
that solved the scrambled-sentence test perceived the outcome to be more
inevitable than participants in a no-outcome control condition and participants
in a no-prime control condition. Furthermore, we found that this increase in
creeping determinism was mediated by the perceived causal strength of the target
antecedent for the occurrence of the outcome, and that the priming-effect did not
occur when an unconditional counterfactual mind-set was activated before. The
results are interpreted as supporting a causal-model theory of the hindsight
bias.
PMID- 25116303
TI - Orthographic overlap and category size in unconscious category priming: comment
on experiment 1c of Van den Bussche and Reynvoet (2007).
AB - Van den Bussche and Reynvoet (2007, Experiment 1) report unconscious priming of
comparable magnitude from novel words belonging to small and large categories,
evidence that they interpret as demonstrating independence from category size of
priming that involves semantic analysis. Three experiments raise the possibility
that the findings in Experiment 1c of Van den Bussche and Reynvoet reflect
subword processing, not semantic analysis. In Experiments 1 and 2, priming was
obtained from primes and targets that shared approximately the same degree of
subword features as in Experiment 1c of Van den Bussche and Reynvoet, but no
priming occurred when sharing of features was minimized. Experiment 3
demonstrated priming driven by subword features when those features were set in
opposition to whole-word meaning. These results indicate that orthographic
overlap must be considered a potentially important confound in findings that
ostensibly support priming mediated by semantic analysis.
PMID- 25116304
TI - Talking about health care: news framing of who is responsible for rising health
care costs in the United States.
AB - This content analysis examines how the American news media have presented the
problem of high and rising health care costs, looking particularly at the
question of who is responsible. More specifically, the authors examine how often
the media have discussed the 5 major causes of the problem: (a) patients, (b)
health care providers, (c) insurance companies, (d) the government, and (e)
pharmaceutical companies. Results revealed that patients were most often
mentioned as the cause of increasing health care costs. The authors also found
that the media's attribution of responsibility to patients has increased over the
years. Overall, media coverage of rising health care costs peaked in 1993, 2004,
and 2009, suggesting that coverage was influenced by newsworthy events (e.g., the
president endorsing legislation or signing a bill into law) that draw the
public's attention.
PMID- 25116305
TI - Prehospital stroke care: limitations of current interventions and focus on new
developments.
AB - BACKGROUND: The global burden of stroke is immense, both in medical and economic
terms. With the aging population and the ongoing industrialization of the third
world, stroke prevalence is expected to increase and will have a major effect on
national health expenditures. Currently, the medical treatment for acute ischemic
stroke is limited to intravenous recombinant tissue plasminogen activator (IV r
tPA), but its time dependency leads to low utilization rates in routine clinical
practice. Prehospital delay contributes significantly to delayed or missed
treatment opportunities in acute stroke. State-of-the-art acute stroke care,
starting in the prehospital phase, could thereby reduce the disease burden and
its enormous financial costs. SUMMARY: The first part of this review focuses on
current education measures for the general public, the emergency medical services
(EMS) dispatchers and paramedics. Although much has been expected of these
measures to improve stroke care, no major effects on prehospital delay or missed
treatment opportunities have been demonstrated over the years. Most
interventional studies showed little or no effect on the onset-to-door time, IV r
tPA utilization rates or outcome, except for prenotification of the receiving
hospital by the EMS. No data are currently available on the cost-effectiveness of
these commonly used measures. In the second part, we discuss new developments for
the improvement of prehospital stroke diagnosis and treatment which could open
new perspectives in the nearby future. These include the implementation of
prehospital telestroke and the deployment of mobile stroke units. These
approaches may improve patient care and could serve as a platform for prehospital
clinical trials. Other opportunities include the implementation of noninvasive
diagnostics (like transcranial ultrasound and blood-borne biomarkers) and the
reevaluation of neuroprotective strategies in the prehospital phase. Key
Messages: Timely initiation of treatment can effectively reduce the medical and
economic burden of stroke and should begin with optimal prehospital stroke care.
For this, prehospital telemedicine is a particularly attractive approach because
it is a scalable solution that has the potential to rapidly optimize acute stroke
care at limited cost.
PMID- 25116307
TI - The intricate interplay between RNA viruses and NF-kappaB.
AB - RNA viruses have rapidly evolving genomes which often allow cross-species
transmission and frequently generate new virus variants with altered pathogenic
properties. Therefore infections by RNA viruses are a major threat to human
health. The infected host cell detects trace amounts of viral RNA and the last
years have revealed common principles in the biochemical mechanisms leading to
signal amplification that is required for mounting of a powerful antiviral
response. Components of the RNA sensing and signaling machinery such as RIG-I
like proteins, MAVS and the inflammasome inducibly form large oligomers or even
fibers that exhibit hallmarks of prions. Following a nucleation event triggered
by detection of viral RNA, these energetically favorable and irreversible
polymerization events trigger signaling cascades leading to the induction of
antiviral and inflammatory responses, mediated by interferon and NF-kappaB
pathways. Viruses have evolved sophisticated strategies to manipulate these host
cell signaling pathways in order to ensure their replication. We will discuss at
the examples of influenza and HTLV-1 viruses how a fascinating diversity of
biochemical mechanisms is employed by viral proteins to control the NF-kappaB
pathway at all levels.
PMID- 25116308
TI - [The current legal status of human organ transplantation].
AB - Advances in medical technology mean that organ donation operations hold the
potential to significantly improve the health status of organ failure patients.
Taiwan registers an average of 100~200 organ donors per year; however, cases
awaiting organ transplant regularly number 8,000 annually. According to the Human
Organ Transplant Act, health professionals are obliged to promote organ donation.
This article introduces the Taiwan Human Organ Transplant Act and illustrates its
implementation and relevant provisions in order to increase general awareness
among healthcare professionals of the legal aspects of organ donation and
transplantation. In addition, this paper cites two judicial decisions that
highlight domestic judicial practice with regard to human organ transplantation.
These include decisions on AIDS organ donation and the ruling not to establish an
organ bank. Healthcare professionals must comprehend the legal requirements and
current status of human organ transplantation in order to play a positive role in
increasing organ donations in Taiwan. A win-win situation for healthcare
provision and patients results when patient safety is the cornerstone of
healthcare provider services.
PMID- 25116309
TI - [New life from the heart: assessment and management of heart transplant
patients].
AB - Patients who receive heart transplantation surgery following end-stage cardiac
failure benefit from efforts to improve their post-surgical quality of life.
Assessing and managing perioperative care play an important role in heart
transplantation. Evaluations of donor and recipient should be conducted carefully
and recommended candidates should by vetted by a qualified heart transplantation
committee. The operative procedure is different from general cardiac surgery, and
organ preservation is a key step in linking the donor to the recipient.
Postoperative infection control and administration of immunosuppressive agents
further affect the outcome of heart transplantation. Based on a review of
articles and our clinical care experience, we focus on the assessment and the
management of heart transplantation in this article.
PMID- 25116310
TI - [Current management and care issues in kidney transplant recipients].
AB - Kidney transplantation is one strategy for treating end-stage renal disease.
Recent advances in perioperative management and immunosuppressive agents as well
as improved understanding of transplant immunology have improved the post-surgery
quality of life of kidney recipients dramatically. However, lifelong monitoring
of renal functions and potential complications is essential to ensure optimal
medical outcomes. Furthermore, the self-care competency of transplant recipients
is a significant factor affecting survival of the graft and the patient over the
long term. All kidney transplant recipients should comply with the self-care
instructions provided by transplantation medical personnel and work to improve
their self-care abilities in order to prevent / detect post-transplant
complications such as rejection, infection, and medical comorbidities as early as
possible. The purpose of this study is to explore the current management and care
issues faced by kidney transplant recipients.
PMID- 25116311
TI - [Factors associated with adherence to immunosuppressive therapy among transplant
recipients].
AB - Advancing medical technology has made organ transplantation an emerging surgical
treatment option for organ failure. Patients who receive transplants must take
immunosuppressive agents for the remainder of their life in order to maintain
good graft function. Failure to take these agents may affect the function of the
transplanted graft, reduce quality of life, and even cause death. Thus,
encouraging patients to take immunosuppressive agents as directed is critical to
minimizing the long-term medical burdens and social costs of organ
transplantation. The purpose of this study is to explore the factors associated
with adherence to immunosuppressive therapy among transplant recipients using the
WHO adherence model. Findings are provided as a reference to health education and
clinical care planners.
PMID- 25116306
TI - Macromolecular transport between the nucleus and the cytoplasm: Advances in
mechanism and emerging links to disease.
AB - Transport of macromolecules between the cytoplasm and the nucleus is critical for
the function of all eukaryotic cells. Large macromolecular channels termed
nuclear pore complexes that span the nuclear envelope mediate the bidirectional
transport of cargoes between the nucleus and cytoplasm. However, the influence of
macromolecular trafficking extends past the nuclear pore complex to transcription
and RNA processing within the nucleus and signaling pathways that reach into the
cytoplasm and beyond. At the Mechanisms of Nuclear Transport biennial meeting
held from October 18 to 23, 2013 in Woods Hole, MA, researchers in the field met
to report on their recent findings. The work presented highlighted significant
advances in understanding nucleocytoplasmic trafficking including how transport
receptors and cargoes pass through the nuclear pore complex, the many signaling
pathways that impinge on transport pathways, interplay between the nuclear
envelope, nuclear pore complexes, and transport pathways, and numerous links
between transport pathways and human disease. The goal of this review is to
highlight newly emerging themes in nuclear transport and underscore the major
questions that are likely to be the focus of future research in the field.
PMID- 25116312
TI - [The effects of multimedia-assisted instruction on the skin care learning of
nurse aides in long-term care facilities].
AB - BACKGROUND: Skin care is an important responsibility of nurse aides in long-term
care facilities, and the nursing knowledge, attitudes, and skills of these aides
significantly affects quality of care. However, the work schedule of nurse aides
often limits their ability to obtain further education and training. Therefore,
developing appropriate and effective training programs for nurse aides is
critical to maintaining and improving quality of care in long-term care
facilities. PURPOSE: This study investigates the effects of multimedia assisted
instruction on the skin care learning of nurse aides working in long-term care
facilities. METHODS: A quasi-experimental design and convenient sampling were
adopted in this study. Participants included 96 nurse aides recruited from 5 long
term care facilities in Taoyuan County, Taiwan. The experimental group received 3
weeks of multimedia assisted instruction. The control group did not receive this
instruction. The Skin Care Questionnaire for Nurse Aides in Long-term Care
Facilities and the Skin Care Behavior Checklist were used for assessment before
and after the intervention. RESULTS: (1) Posttest scores for skin care knowledge,
attitudes, behavior, and the skin care checklist were significantly higher than
pretest scores for the intervention group. There was no significant difference
between pretest and posttest scores for the control group. (2) A covariance
analysis of pretest scores for the two groups showed that the experimental group
earned significantly higher average scores than their control group peers for
skin care knowledge, attitudes, behavior, and the skin care checklist.
CONCLUSIONS: The multimedia assisted instruction demonstrated significant and
positive effects on the skin care leaning of nurse aides in long-term care
facilities. This finding supports the use of multimedia assisted instruction in
the education and training of nurse aides in long-term care facilities in the
future.
PMID- 25116313
TI - [Health networks for new immigrants in taiwan].
AB - BACKGROUND: Healthcare and studies related to new immigrants in Taiwan have been
influenced by immigrant reproductive health management policy. Some nursing
scholars have criticized the top-down approach as potentially not addressing the
actual healthcare needs of these immigrants. Medical institutions are being
called upon to provide culturally appropriate care. PURPOSE: Using health
networks as its conceptual framework, this paper explores the definition of
health as perceived by recent immigrants to Taiwan and their perspectives on
seeking and maintaining health. METHODS: This paper uses participant observation
and depth-interviews to assess how recent immigrants from Mainland China,
Vietnam, and Indonesia seek health in their new homeland, evaluate the
differences between the healthcare systems in their former and current countries,
and recommend actions necessary to ensure the health and wellbeing of this
population. RESULTS: The findings are grouped into three themes: "the differences
between immigrants and Taiwanese in health care," "local health networks", and
"transnational health networks." These themes reflect the views on health and
health care of recent female immigrants to Taiwan. CONCLUSIONS: CONCLUSION:
Through the actions and narratives of these immigrants, this paper suggests the
priority concerns that immigrant agencies should address in order to maintain the
health of this group. Additionally, findings give some insight into the gender
and ethnic characteristics of immigrant health networks. Immigrants construct and
rely upon social relations, cultural identity, and resources to maintain their
wellbeing. This study contributes to transcultural nursing theory and to in
service training and helps medical practitioners and nurses provide culturally
appropriate care.
PMID- 25116314
TI - [The physical activity and life healing in psychiatric patients: taijiguan as an
example].
AB - BACKGROUND: Chronic psychiatric patients tend to have cognitive and functional
impairments. Participation in physical activity has been shown to improve their
health and independence. Regular practice of Taijiquan may help improve mood and
life stresses, promoting physical and mental health. PURPOSE: This research
explores the effect of a 13-week Taijiquan learning program on the daily life
experience of chronic psychiatric patients. The process and the essential meaning
of the entire learning experiences are presented. METHODS: Data were collected
from a psychiatric daycare center at a Teaching Hospital in Taipei. The 6
patients who participated in this study included 3 with bipolar disorders and 3
with schizophrenia. Narrative inquiry and focus-group interviews were used for
qualitative data collection and analysis. RESULTS: The initial results of
participant experiences were categorized into 3 themes: 1. Learning kung fu in
the Taijiquan; 2. Releasing binding through the practice of Taijiquan; and 3.
Pursuit of excellence through the learning of Taijiquan. The views of illness,
body, and interpersonal interaction as well as the three stages of dilemma,
transcendence / acclimation, and acquaintance for the psychiatric patients and
their Taijiquan's learning world were described and the potential therapeutic
effects on the body and daily life of these patients were explored. CONCLUSIONS /
IMPLICATIONS FOR PRACTICE: Learning Taijiquan is highly challenging for the
novice, especially those with chronic psychiatric illnesses. However, after
familiarization with the postural actions and key concepts of this exercise,
Taijiquan facilitated body relaxation, heightened perception, and postural
balance. Consequently, this exercise stabilized the mood, disease status, and
capacity for handling interpersonal relationships of participants and
consequently may enhance their long-term life quality and disease recovery
status. Results of this study recommend strongly that Taijiquan be included as a
therapeutic activity for psychiatric patients to improve their health, healing,
and recovery.
PMID- 25116315
TI - [Psychometric testing of the chinese version of the readiness for hospital
discharge scale].
AB - BACKGROUND: Little has been published in the literature regarding how patients
self-evaluate their degree of readiness for hospital discharge. Furthermore,
there is currently no self-evaluation tool available in Chinese able to assess
the discharge readiness of patients. PURPOSE: This study was used to
psychometrically test the Chinese version of the readiness for hospital discharge
scale (RHDS_C). METHODS: This study used a cross-sectional design. Two samples
were recruited in a two-stage process at two hospitals in Southern Taiwan. Two
hundred and twenty-three patients with a diagnosis of either colorectal cancer or
hepatic cancer were used to conduct an exploratory factor analysis (EFA) in the
first stage of the study. Another 323 patients with a diagnosis of stroke were
used conduct a confirmatory factor analysis (CFA). The instrument used was the
Readiness for Hospital Discharge Scale (RHDS) developed by Weiss & Piacentine.
RESULTS: RHDS_C consists of three subscales: personal status (4 items), coping
ability (4 items), and expected support (4 items) adapted from the CFA. The
assessed goodness-of-fit index (GFI = .92, AGFI = .88, NFI = .97) indicate the
model fit the data well based upon the CFA. Criterion-related validity was
supported by the correlation between the original RHDS and the RHDS_C (r = .96, p
< .001). The Cronbach's alpha coefficients were .89 for the overall scale and
.73, .90, and .89 for the 3 subscales, respectively. CONCLUSIONS / IMPLICATIONS
FOR PRACTICE: This study confirms the validity of the RHDS_C and suggests this
instrument is able to reliably assess the readiness of patients for discharge
from the hospital. We recommend the scale be applied in the clinical setting to
evaluate the discharge readiness of hospital patients.
PMID- 25116316
TI - [A project to reduce the incidence of intubation care errors among foreign health
aides].
AB - BACKGROUND & PROBLEMS: Foreign health aides are the main providers of care for
the elderly and the physically disabled in Taiwan. Correct care skills improve
patient safety. In 2010, the incidence of mistakes among foreign health aides in
our hospital unit was 58% for nasogastric tube care and 57% for tracheostomy tube
care. A survey of foreign health aides and nurses in the unit identified the main
causes of these mistakes as: communication difficulties, inaccurate instructions
given to patients, and a lack of standard operating procedures given to the
foreign health aides. PURPOSE: This project was designed to reduce the rates of
improper nasogastric tube care and improper tracheostomy tube care to 20%,
respectively. METHODS: This project implemented several appropriate measures. We
produced patient instruction hand-outs in Bahasa Indonesia, established a
dedicated file holder for Bahasa Indonesian tube care reference information,
produced Bahasa Indonesian tube-care-related posters, produced a short film about
tube care in Bahasa Indonesian, and established a standardized operating
procedure for tube care in our unit. RESULTS: Between December 15th and 31st,
2011, we audited the performance of a total of 32 foreign health aides for proper
execution of nasogastric tube care (21 aides) and of proper execution of
tracheostomy tube care (11 aides). Patients with concurrent nasogastric and
tracheostomy tubes were inspected separately for each care group. The incidence
of improper care decreased from 58% to 18% nasogastric intubation and 57% to 18%
for tracheostomy intubation. CONCLUSIONS: This project decreased significantly
the incidence of improper tube care by the foreign health aides in our unit.
Furthermore, the foreign health aides improved their tube nursing care skills.
Therefore, this project improved the quality of patient care.
PMID- 25116317
TI - [Reducing the incidence of needlestick injuries due to insulin pen injectors
among self-users in the outpatient clinic setting].
AB - BACKGROUND & PROBLEM: The rising number of people practicing insulin self
injection at home has led to increasing numbers of needlestick injuries due to
inadequate self-injection skills among these patients. To reduce needlestick
injuries at home, patients should not recap needles and should adopt proper
needle disposal practices. A random survey of 80 outpatients currently using
insulin pen injectors at home conducted between February and April 2012 found
that 70% self-reported suffering needlestick incidents. Data analysis indicated
the principal causes of these incidents were the lack of standard operating
procedures, the absence of educational training, the shortage of educational
instruction sheets for patients, and the inadequate skills and tools available to
patients for disposing of needles safely at home. PURPOSE: The aim of this
project was to decrease the needlestick incidence rate for outpatients that use
insulin pen injectors in order to increase overall patient safety. RESOLUTION:
The project team established a pen injector standard operation procedure (SOP),
conducted an educational training program, developed nursing instruction sheets
for patients, designed and distributed needle disposal containers to patients,
and taught patients the correct techniques for the disposing of needles at home.
RESULTS: The needlestick incidence rate decreased from 70% pretest to 2.6%
following implementation of the abovementioned measures. CONCLUSIONS: This
project effectively reduced the needlestick rate attributable to insulin pen
injectors. The authors hope that other departments will adopt this approach in
order to improve patient safety.
PMID- 25116318
TI - [Consent vs. Assent: Ethical Considerations Related to Bone Marrow
Transplantation in Adolescents].
AB - Bone marrow transplantation (BMT) is a frequently considered treatment option for
terminal childhood cancer. However, the side effects of BMT frequently cause
short- and long-term physical discomfort and spiritual suffering, which
significantly impact patient quality of life. In Taiwan, parental consent is
typically given priority over the assent of children in medical decisions. This
article uses a case of an adolescent patient with neuroblastoma undergoing BMT to
discuss the best interest standard and contradictions between the consent of
parents and the assent of their children. This article argues that medical staffs
are responsible to protect the right of children to fully consider and influence
the decisions related to their treatment options. Medical staffs should
communicate to parents the importance of their children's assent and promote
better communication between parents and their children in order to achieve the
best outcome for the family as a whole. When mutual communication is unable to
resolve conflicts between parents and their children, we recommend seeking
assistance from the ethics committee in the hospital.
PMID- 25116319
TI - [Clinical care of lung cancer patients with body image changes after targeted
therapy].
AB - Lung cancer has a relatively short survival prognosis and advanced disease
progression. Therefore, targeted therapy has become one of the most frequent
treatments of this disease. Targeted therapy has several features that
effectively extend the survival period; is easy to apply and use; and has fewer
side effects than chemotherapy. Therefore, this therapy approach has become the
preferred choice of patients with advanced lung cancer. However, current targeted
therapies like Iressa and Tarceva produce side effects such as skin dryness and
acneiform eruption that may bother patients. These side effects may further cause
patient concern over negative changes in their body image, and these concerns may
influence their work and social lives. Additionally, some patients treated with
targeted therapy worry about their chances of survival if they reduce or stop the
medication to avoid the side effects. Consequently, patients may struggle with
both physical and psychological impacts, and may have problems sustaining a good
quality of life. This article focuses on delivering relevant information to
patients receiving targeted therapy who suffer from dermatological toxicity and
damage to their body image. We demonstrate an assessment tool and information to
help patients cope with physical and psychosocial issues through daily skin care
routines, mental / psychological supports, and cognitive behavior therapy. These
measures may help patients rebuild a positive self-concept. We plan to develop
further associated training to provide professionals / care providers with the
appropriate knowledge and skills to care for cancer patients in a resource
limited environment so that they may improve the quality of nursing care for
patients with body image changes.
PMID- 25116320
TI - [Applying Swanson's Caring Theory to Manage Spiritual Distress in a Patient With
Terminal Lung Cancer].
AB - This case report shares a nursing experience that applied Swanson's Caring Theory
as part of the care regimen for a terminal lung cancer patient suffering from
spiritual distress. The nursing care was provided from March 20th to April 25th,
2012. Data were collected through observation and conversation and recorded using
sketches and written notes. The nurse assessed the patient's relationships with
the self, with others, with the environment, and with God in accordance with
Stoll's spiritual interrelatedness hypothesis. Several spiritual distresses were
reported. Interventions such as "knowing", "being with", "doing for", "enabling"
and "maintaining belief" were applied to manage the patient's spiritual distress
and address spiritual needs. This case report is intended to help increase the
awareness and sensitivity of nurses to patients' spiritual needs and to help
nurses provide effective spiritual care.
PMID- 25116325
TI - Flow-compensated intravoxel incoherent motion diffusion imaging.
AB - PURPOSE: The pseudo-diffusion coefficient D* in intravoxel incoherent motion
(IVIM) imaging was found difficult to seize. Flow-compensated diffusion gradients
were used to test the validity of the commonly assumed biexponential limit and to
determine not only D*, but also characteristic timescale tau and velocity v of
the incoherent motion. THEORY AND METHODS: Bipolar and flow-compensated diffusion
gradients were inserted into a flow-compensated single-shot EPI sequence. Images
were obtained from a pipe-shaped flow phantom and from healthy volunteers. To
calculate the IVIM signal outside the biexponential limit, a formalism based on
normalized phase distributions was developed. RESULTS: The flow-compensated
diffusion gradients caused less signal attenuation than the bipolar ones. A
signal dependence on the duration of the flow-compensated gradients was found at
low b-values in the volunteer datasets. The characteristic IVIM parameters were
estimated to be v = 4.60 +/- 0.34 mm/s and tau = 144 +/- 10 ms for liver and v =
3.91 +/- 0.54 mm/s and tau = 224 +/- 47 ms for pancreas. CONCLUSION: Our results
strongly indicate that the biexponential limit does not adequately model the
diffusion signal in liver and pancreas. By using both bipolar and flow
compensated diffusion gradients of different duration, the characteristic
timescale and velocity of the incoherent motion can be determined.
PMID- 25116322
TI - Oral human papillomavirus infection in men might contribute to HPV serology.
AB - The prospective Finnish Family HPV Study evaluated the dynamics of human
papillomavirus (HPV) infection within families. Here, we focused on HPV serology
in men. Seroprevalence at baseline, seroconversion and decay of low-risk (LR)
HPV6 and 11, and high risk (HR)-HPV16, 18 and 45 L1 antibodies in 122 men at 12,
24 and 36 months were determined using Luminex-based multiplex HPV serology, and
correlated with demographic data. At baseline, seropositivity to HPV6, 11, 16, 18
and 45 was observed in 41.0, 11.5, 23.0, 13.9 and 5.7 % of the men, respectively.
In univariate analysis, LR-HPV seropositivity was related to smoking status,
history of genital warts and being seropositive to HR-HPV. Oral HR-HPV DNA and
baseline LR-HPV seropositivity predicted HR-HPV seropositivity. Seroconversion to
HPV6, 11, 16, 18 and 45 antigens during follow-up was found in 24.6, 11.5, 5.7,
5.7 and 0.8 %, respectively. Seroconversion to LR-HPV was negatively related to a
higher number of children and oral sex, and positively associated with
seroconversion to HR-HPV. In multivariate analysis, the same predictors remained
significant except for the number of children. In univariate generalised
estimating equations (GEE) for HR-HPV, being seroconverted to LR-HPV was the only
predictor, but lost its significance in multivariate analyses. Decay of all HPV
L1 antibodies was rare and observed in 0-2 %. The HPV antibody profile in men was
dominated by response to HPV6, also showing the highest cumulative
seroconversion. Oral HPV infection might affect HPV serology: (1) HPV DNA in oral
mucosa is associated with baseline HR-HPV seropositivity and (2) practising oral
sex significantly reduces longitudinal seroconversion to HPV6 and/or 11.
PMID- 25116326
TI - Interceptive [4 + 1] annulation of in situ generated 1,2-diaza-1,3-dienes with
diazo esters: direct access to substituted mono-, bi-, and tricyclic 4,5
dihydropyrazoles.
AB - In situ derived acyclic and cyclic 1,2-diaza-1,3-dienes (DDs) were engaged in
interceptive [4 + 1] annulation strategy with diazo esters (DEs). The catalytic
activity of inexpensive copper(II) chloride allows the direct synthesis of mono-,
bi-, and tricyclic 4,5-dihydropyrazole-5-carboxylic acid derivatives in a process
that circumvents the use of an anhydrous and inert atmosphere.
PMID- 25116321
TI - Retinal dendritic cell recruitment, but not function, was inhibited in MyD88 and
TRIF deficient mice.
AB - BACKGROUND: Immune system cells are known to affect loss of neurons due to injury
or disease. Recruitment of immune cells following retinal/CNS injury has been
shown to affect the health and survival of neurons in several models. We detected
close, physical contact between dendritic cells and retinal ganglion cells
following an optic nerve crush, and sought to understand the underlying
mechanisms. METHODS: CD11c-DTR/GFP mice producing a chimeric protein of
diphtheria toxin receptor (DTR) and GFP from a transgenic CD11c promoter were
used in conjunction with mice deficient in MyD88 and/or TRIF. Retinal ganglion
cell injury was induced by an optic nerve crush, and the resulting interactions
of the GFPhi cells and retinal ganglion cells were examined. RESULTS: Recruitment
of GFPhi dendritic cells to the retina was significantly compromised in MyD88 and
TRIF knockout mice. GFPhi dendritic cells played a significant role in clearing
fluorescent-labeled retinal ganglion cells post-injury in the CD11c-DTR/GFP mice.
In the TRIF and MyD88 deficient mice, the resting level of GFPhi dendritic cells
was lower, and their influx was reduced following the optic nerve crush injury.
The reduction in GFPhi dendritic cell numbers led to their replacement in the
uptake of fluorescent-labeled debris by GFPlo microglia/macrophages. Depletion of
GFPhi dendritic cells by treatment with diphtheria toxin also led to their
displacement by GFPlo microglia/macrophages, which then assumed close contact
with the injured neurons. CONCLUSIONS: The contribution of recruited cells to the
injury response was substantial, and regulated by MyD88 and TRIF. However, the
presence of these adaptor proteins was not required for interaction with neurons,
or the phagocytosis of debris. The data suggested a two-niche model in which
resident microglia were maintained at a constant level post-optic nerve crush,
while the injury-stimulated recruitment of dendritic cells and macrophages led to
their transient appearance in numbers equivalent to or greater than the resident
microglia.
PMID- 25116328
TI - The CROWN Initiative: journal editors invite researchers to develop core outcomes
in women's health.
PMID- 25116329
TI - Predictors of non-adherence to follow-up visits and deferasirox chelation therapy
among jordanian adolescents with Thalassemia major.
AB - Poor adherence to treatment can have negative effects on outcomes and heath care
cost. However, little is known about the factors that impact adherence to
deferasirox chelation therapy. The aims of this study were to identify rates and
predictors of non-adherence to medical regimen among thalassemia major
adolescents on deferasirox oral chelation therapy by using subjective (self
reporting) and objective (serum ferritin and follow-up visits) measures.
Convenient samples of 164 adolescents, aged 12-19 years were recruited from three
National Thalassemia Centers in Jordan. Patients were interviewed using a four
section questionnaire and the medical records were checked. Results indicated
that rate of adherence according to self-report was (73%); while to follow-up
medical appointments and serum ferritin level rates was 57% and 47%,
respectively. One-third of participant adolescents (n = 52) were psychologically
impaired. Multivariate analysis showed that factors affecting adolescent non
adherence to deferasirox chelation therapy is different from that affecting
adherence to follow-up visits. In general, adolescents more than 16 years old,
presence of sibling with thalassemia, lack of parental monitoring, lower family
income, decrease frequency of blood transfusion, and psychological impairment
were found significant predictors of non-adherence among adolescents. Disease
knowledge was not associated with adherence status of the adolescents. Clinician
should be aware of high prevalence of low adherence to chelation therapy during
adolescent years. Nurses need to regularly assess, monitor, and promote adherence
behavior that might impact patients' outcomes.
PMID- 25116327
TI - Grouping annotations on the subcellular layered interactome demonstrates enhanced
autophagy activity in a recurrent experimental autoimmune uveitis T cell line.
AB - Human uveitis is a type of T cell-mediated autoimmune disease that often shows
relapse-remitting courses affecting multiple biological processes. As a
cytoplasmic process, autophagy has been seen as an adaptive response to cell
death and survival, yet the link between autophagy and T cell-mediated
autoimmunity is not certain. In this study, based on the differentially expressed
genes (GSE19652) between the recurrent versus monophasic T cell lines, whose
adoptive transfer to susceptible animals may result in respective recurrent or
monophasic uveitis, we proposed grouping annotations on a subcellular layered
interactome framework to analyze the specific bioprocesses that are linked to the
recurrence of T cell autoimmunity. That is, the subcellular layered interactome
was established by the Cytoscape and Cerebral plugin based on differential
expression, global interactome, and subcellular localization information. Then,
the layered interactomes were grouping annotated by the ClueGO plugin based on
Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The analysis
showed that significant bioprocesses with autophagy were orchestrated in the
cytoplasmic layered interactome and that mTOR may have a regulatory role in it.
Furthermore, by setting up recurrent and monophasic uveitis in Lewis rats, we
confirmed by transmission electron microscopy that, in comparison to the
monophasic disease, recurrent uveitis in vivo showed significantly increased
autophagy activity and extended lymphocyte infiltration to the affected retina.
In summary, our framework methodology is a useful tool to disclose specific
bioprocesses and molecular targets that can be attributed to a certain disease.
Our results indicated that targeted inhibition of autophagy pathways may perturb
the recurrence of uveitis.
PMID- 25116330
TI - Iridium-catalyzed C-H borylation of pyridines.
AB - The iridium-catalysed C-H borylation is a valuable and attractive method for the
preparation of aryl and heteroaryl boronates. However, application of this
methodology for the preparation of pyridyl and related azinyl boronates can be
challenged by low reactivity and propensity for rapid protodeborylation,
particularly for a boronate ester ortho to the azinyl nitrogen. Competition
experiments have revealed that the low reactivity is due to inhibition of the
active catalyst through coordination of the azinyl nitrogen lone pair at the
vacant site on the iridium. This effect can be overcome through the incorporation
of a substituent at C-2. Moreover, when this is sufficiently electron-withdrawing
protodeborylation is sufficiently slowed to permit isolation and purification of
the C-6 boronate ester. Following functionalization, reduction of the directing C
2 substituent provides the product arising from formal ortho borylation of an
unhindered pyridine ring.
PMID- 25116332
TI - Summary health statistics for u.s. Children: national health interview survey,
2011.
AB - Objectives-This report presents both age-adjusted and unadjusted statistics from
the 2011 National Health Interview Survey (NHIS) on selected health measures for
children under age 18 years, classified by sex, age, race, Hispanic origin,
family structure, parent education, family income, poverty status, health
insurance coverage, place of residence, region, and current health status. Topics
included are asthma, allergies, learning disability, attention deficit
hyperactivity disorder (ADHD), prescription medication use for at least 3 months,
respondent-assessed health status, school days missed due to illness or injury,
usual place of health care, time since last contact with a health care
professional, selected measures of health care access, emergency room visits, and
dental care. Data Source-NHIS is a multistage probability sample survey conducted
annually by interviewers of the U.S. Census Bureau for the Centers for Disease
Control and Prevention's National Center for Health Statistics and is
representative of the civilian noninstitutionalized population of the United
States. This report analyzes data from two of the main components of NHIS: the
family core, in which data are collected for all family members by interviewing
an adult family respondent, and the sample child core, in which additional health
information is collected about a randomly selected child (the ''sample child'')
from an adult proxy familiar with the child's health. Selected Highlights-In
2011, most U.S. children under age 18 years had excellent or very good health
(83%). However, 7% of children had no health insurance coverage, and 3% of
children had no usual place of health care. Six percent of children had unmet
dental need because their families could not afford dental care. Fourteen percent
of children had ever been diagnosed with asthma. An estimated 8% of children aged
3-17 had a learning disability, and an estimated 9% of children had ADHD.
PMID- 25116331
TI - Prognostic significance of complex karyotype and monosomal karyotype in adult
patients with acute lymphoblastic leukemia treated with risk-adapted protocols.
AB - BACKGROUND: The karyotype is a predictor of outcomes in adults with acute
lymphoblastic leukemia (ALL). The unfavorable prognostic significance of complex
karyotype (CK) has been reported, whereas the prognostic relevance of monosomal
karyotype (MK) has not been consistently evaluated. We aimed to assess the
prognostic value of CK and MK in adults with ALL treated with risk-adapted
protocols of the Spanish PETHEMA Group. METHODS: The karyotypes of 881 adult ALL
patients treated according to the protocols of the PETHEMA Group between 1993 and
2012 were centrally reviewed. CK and MK were assessed according to Moorman's
criteria, and Breem's criteria, respectively. Specific analyses according to the
risk groups and to the presence of t(9:22) were performed. RESULTS: Of 364
evaluable patients 33 (9.2%) had CK, and 68 of 535 evaluable patients (12.8%) had
MK. Complete remission rate, remission duration, and overall survival were not
significantly different according to the presence of CK or MK in the whole
series, according to the B or T lineage, in the high-risk group, or in patients
with t(9;22), regardless of imatinib treatment, and in patients who received
chemotherapy alone or chemotherapy followed by stem cell transplantation
CONCLUSIONS: Our study shows that CK and MK were not associated with a worse
prognosis in adult patients with ALL treated with risk-adapted or subtype
oriented protocols. In patients with Ph+ ALL, MK did not have an impact on
prognosis irrespective of imatinib treatment.
PMID- 25116333
TI - Ordered structure and thermal expansion in tungsten bronze
Pb2K(0.5)Li(0.5)Nb5O15.
AB - The crystal structure and thermal expansion behaviors of a new tetragonal
tungsten bronze (TTB) ferroelectric, Pb2K(0.5)Li(0.5)Nb5O15, were systematically
investigated by selected-area electron diffraction (SAED), neutron powder
diffraction, synchrotron X-ray diffraction (XRD), and high-temperature XRD. SAED
and Rietveld refinement reveal that Pb2K(0.5)Li(0.5)Nb5O15 displays a
commensurate superstructure of simple orthorhombic TTB structure at room
temperature. The structure can be described with space group Bb21m. The
transition to a paraelectric phase (P4/mbm) occurs at 500 degrees C. Compared
with Pb2KNb5O15 (PKN), the substitution of 0.5K(+) with small 0.5Li(+) into PKN
causes the tilting of NbO6 octahedra away from the c axis with Deltatheta ~ 10
degrees and raises the Curie temperature by 40 degrees C, and the negative
thermal expansion coefficient along the polar b axis increases more than 50% in
the temperature range 25-500 degrees C. We present that, by introduction of
Li(+), the enhanced spontaneous polarization is responsible for the enhanced
negative thermal expansion along the b axis, which may be caused by more Pb(2+)
in the pentagonal caves.
PMID- 25116334
TI - ACE consensus meeting report: culture systems.
AB - The UK Association of Clinical Embryologists held a workshop on Culture Systems
for assisted conception in Sheffield on 22 May 2013. The meeting was organised in
the light of the availability of numerous commercial products for the culture of
human preimplantation embryos in vitro and the absence of data comparing the
performance of these products. Expert opinions were presented, along with survey
data provided by participating IVF Centres. The workshop highlighted the lack of
a sound evidence base to support the selection of any one commercial product over
another, and raised concerns over the lack of information defining precisely the
composition of media, and the potential for adverse long-term effects of such
products following their use in assisted conception.
PMID- 25116335
TI - Drastic change in China's lakes and reservoirs over the past decades.
AB - Using remote sensing images, we provided the first complete picture of freshwater
bodies in mainland China. We mapped 89,700 reservoirs, covering about 26,870
km(2) and approximately 185,000 lakes with a surface area of about 82,232 km(2).
Despite relatively small surface area, the total estimated storage capacity of
reservoirs (794 km(3)) is triple that of lakes (268 km(3)). Further analysis
indicates that reservoir construction has made the river systems strongly
regulated: only 6% of the assessed river basins are free-flowing; 20% of assessed
river basins have enough cumulative reservoir capacity to store more than the
entire annual river flow. Despite the existence of 2,721 lakes greater than 1
km(2), we found that about 50 lakes greater than km(2) have formed on the Tibetan
Plateau resulting from climate change. More than 350 lakes of >=1 km(2) vanished
in four other major lake regions. Although the disappearance of lakes happened in
the context of global climate change, it principally reflects the severe
anthropogenic impacts on natural lakes, such as, the excessive plundering of
water resources on the Inner Mongolia-Xinjiang Plateau and serious destruction
(land reclamation and urbanization) on the eastern plains.
PMID- 25116337
TI - Humidity effect of domain wall roughening behavior in ferroelectric copolymer
thin films.
AB - We have demonstrated that domain switching in ferroelectric copolymer films can
be significantly affected by humidity. With increasing relative humidity (RH), we
observed larger domains with highly irregular boundaries as a result of lateral
spreading of the tip-induced electric field that originates from water
adsorption. Fractal dimension study of irregular domains reveals that the fractal
dimension is higher in cases where the RH is higher. The results show that the RH
is one of the major switching parameters in ferroelectric copolymers, and
therefore could allow clear understanding with regard to domain switching
behavior in the ferroelectric copolymer films under ambient conditions.
PMID- 25116336
TI - Arsenic trioxide reactivates proteasome-dependent degradation of mutant p53
protein in cancer cells in part via enhanced expression of Pirh2 E3 ligase.
AB - The p53 gene is mutated in more than 50% of human tumors. Mutant p53 exerts an
oncogenic function and is often highly expressed in cancer cells due to evasion
of proteasome-dependent degradation. Thus, reactivating proteasome-dependent
degradation of mutant p53 protein is an attractive strategy for cancer
management. Previously, we found that arsenic trioxide (ATO), a drug for acute
promyelocytic leukemia, degrades mutant p53 protein through a proteasome pathway.
However, it remains unclear what is the E3 ligase that targets mutant p53 for
degradation. In current study, we sought to identify an E3 ligase necessary for
ATO-mediated degradation of mutant p53. We found that ATO induces expression of
Pirh2 E3 ligase at the transcriptional level. We also found that knockdown of
Pirh2 inhibits, whereas ectopic expression of Pirh2 enhances, ATO-induced
degradation of mutant p53 protein. Furthermore, we found that Pirh2 E3 ligase
physically interacts with and targets mutant p53 for polyubiquitination and
subsequently proteasomal degradation. Interestingly, we found that ATO cooperates
with HSP90 or HDAC inhibitor to promote mutant p53 degradation and growth
suppression in tumor cells. Together, these data suggest that ATO promotes mutant
p53 degradation in part via induction of the Pirh2-dependent proteasome pathway.
PMID- 25116338
TI - Silence that can be dangerous: a vignette study to assess healthcare
professionals' likelihood of speaking up about safety concerns.
AB - PURPOSE: To investigate the likelihood of speaking up about patient safety in
oncology and to clarify the effect of clinical and situational context factors on
the likelihood of voicing concerns. PATIENTS AND METHODS: 1013 nurses and doctors
in oncology rated four clinical vignettes describing coworkers' errors and rule
violations in a self-administered factorial survey (65% response rate). Multiple
regression analysis was used to model the likelihood of speaking up as outcome of
vignette attributes, responder's evaluations of the situation and personal
characteristics. RESULTS: Respondents reported a high likelihood of speaking up
about patient safety but the variation between and within types of errors and
rule violations was substantial. Staff without managerial function provided
significantly higher levels of decision difficulty and discomfort to speak up.
Based on the information presented in the vignettes, 74%-96% would speak up
towards a supervisor failing to check a prescription, 45%-81% would point a
coworker to a missed hand disinfection, 82%-94% would speak up towards nurses who
violate a safety rule in medication preparation, and 59%-92% would question a
doctor violating a safety rule in lumbar puncture. Several vignette attributes
predicted the likelihood of speaking up. Perceived potential harm, anticipated
discomfort, and decision difficulty were significant predictors of the likelihood
of speaking up. CONCLUSIONS: Clinicians' willingness to speak up about patient
safety is considerably affected by contextual factors. Physicians and nurses
without managerial function report substantial discomfort with speaking up.
Oncology departments should provide staff with clear guidance and trainings on
when and how to voice safety concerns.
PMID- 25116339
TI - Redox-initiated hydrogel system for detection and real-time imaging of
cellulolytic enzyme activity.
AB - Understanding the process of biomass degradation by cellulolytic enzymes is of
urgent importance for biofuel and chemical production. Optimizing pretreatment
conditions and improving enzyme formulations both require assays to quantify
saccharification products on solid substrates. Typically, such assays are
performed using freely diffusing fluorophores or dyes that measure reducing
polysaccharide chain ends. These methods have thus far not allowed spatial
localization of hydrolysis activity to specific substrate locations with
identifiable morphological features. Here we describe a hydrogel reagent
signaling (HyReS) system that amplifies saccharification products and initiates
crosslinking of a hydrogel that localizes to locations of cellulose hydrolysis,
allowing for imaging of the degradation process in real time. Optical detection
of the gel in a rapid parallel format on synthetic and natural pretreated solid
substrates was used to quantify activity of T. emersonii and T. reesei enzyme
cocktails. When combined with total internal reflection fluorescence microscopy
and AFM imaging, the reagent system provided a means to visualize enzyme activity
in real-time with high spatial resolution (<2 MUm). These results demonstrate the
versatility of the HyReS system in detecting cellulolytic enzyme activity and
suggest new opportunities in real-time chemical imaging of biomass
depolymerization.
PMID- 25116340
TI - Smart composite nanosheets with adaptive optical properties.
AB - We report efficient design and facile synthesis of size-tunable organic/inorganic
nanosheets, via a straightforward liquid exfoliation-adsorption process, of a
near percolating gold (Au) thin film deposited onto a branched polyethylenimine
(bPEI) matrix. The nanosheets are stiff enough to sustain their two-dimensional
(2D) nature in acidic conditions, yet flexible enough to undergo a perfect
reversible shape transformation to 1D nanoscrolls in alkaline conditions. The
shape transformations, and associated optical property changes, at different
protonation states are monitored by transmission electron microscopy (TEM),
atomic force microscopy (AFM), UV-visible spectroscopy and zeta potential
measurements. Because of their large surface area, both nanosheets and
nanoscrolls could be used as capturing substrates for surface-enhanced Raman
scattering (SERS) applications.
PMID- 25116341
TI - DNA sequence-dependent photoluminescence enhancement in a cationic conjugated
polyelectrolyte.
AB - DNA sequence-dependent photoluminescence enhancement is found for a cationic
polyelectrolyte complexed with single stranded DNA and described as a result of
an interplay between electrostatic attraction and the pi-pi stacking between the
polyelectrolyte's backbone and DNA's bases.
PMID- 25116342
TI - A trial to extend breast cancer screening may be unethical.
PMID- 25116343
TI - Evidence of increased centrally enhanced bladder compliance with ageing in a
mouse model.
AB - OBJECTIVE: To test the hypothesis that ageing is associated with increasing
neurogenic enhancement of bladder filling compliance. MATERIALS AND METHODS:
Female B6 mice (aged 2, 12, 22 and 26 months) underwent cystometry while alive
and immediately after death. Bladder compliance was calculated from pressure-time
data. Pressure data were transformed using Fast Fourier Transform to obtain power
spectra of bladder pressure variations attributable to contractile activity
during filling in both alive and dead mice. A cut-off frequency (CF) was
determined for each mouse, above which any power content would be primarily
neurogenic. Compliance and power spectra results were compared among age groups,
and correlations sought. RESULTS: A reversible loss of bladder compliance and non
voiding contractile (NVC) activity followed abolition of voiding reflexes in
female colony mice in all age groups. Bladder filling compliance increased with
age in urethane-anaesthetised and post-mortem conditions, and more so in the
former. Power below the CF did not significantly vary with age. Neurogenic power
increased with age, and significantly correlated with compliance. CONCLUSIONS: An
increase in neurogenic power during filling accompanies increased centrally
mediated compliance enhancement with age. A bladder control model in which brain
processes related to micturition may compensate for age-associated changes;
thereby preserving voiding function is suggested. Urinary dysfunction could be
viewed as the result of homeostatic failure rather than strictly end-organ
pathology.
PMID- 25116345
TI - The position of the tibia tubercle in 0 degrees -90 degrees flexion: comparing
patients with patella dislocation to healthy volunteers.
AB - PURPOSE: The aim of this study was to measure the tibia tubercle trochlea groove
distance (TT-TG) as a function of knee flexion. Our hypothesis was that there is
a different pattern in healthy volunteers and patients with patella instability
(PFI). METHODS: Thirty-six knees of 30 patients with at least one dislocation of
the patella and 30 knees of 30 healthy volunteers as control group were analysed
with magnetic resonance imaging by three different observers. The TT-TG was
measured in steps of 15 degrees between 0 degrees and 90 degrees of knee
flexion. Furthermore, the alignment of the leg (MA), the femur torsion (FTor) and
the tibia torsion (TTor) was calculated. RESULTS: The TT-TG was higher in
patients compared to volunteers and in extension compared to flexion. This
difference was statistically significant (p<0.05). Most of the patients with a TT
TG above 20 mm in extension showed a high decrease in flexion to normal values.
In some patients, this compensating mechanism fails. MA, FTor and TTor were not
different in patients and control group (n.s.). CONCLUSION: The TT-TG distance is
dynamic and decreased significantly during flexion in knees with PFI and healthy
volunteers. However, there were a small number of patients in the PFI group where
this compensation mechanism did not work. Therefore, the decision to perform a
tibia tubercle osteotomy should not be based on one single measurement in
extension or 30 degrees of knee flexion. LEVEL OF EVIDENCE: II.
PMID- 25116346
TI - Patellofemoral arthrodesis as pain relief in extreme patella alta.
AB - PURPOSE: There is no golden standard management for neglected, chronic patellar
tendon rupture as they are fairly rare. Nevertheless, accompanying pain can be
highly debilitating. By presenting a case of patellar tendon repair, the
exceptional results of a patellofemoral arthrodesis are described. METHODS: A
patient presented herself with a sustained patellar tendon rupture which was
neglected for several years, causing a complete extensor mechanism dysfunction.
Her most debilitating complaint was pain. As ligament reconstruction in this case
was not possible, patellofemoral arthrodesis was aimed for. The pain resulting
from micromotions was subsided by implementing a unique technique using a lock
key principle to obtain a patellofemoral arthrodesis. RESULTS: The procedure
proceeded without complications. The patient followed a regular post-operative
plan and is now successful in maximum weight bearing her knee without pain.
CONCLUSIONS: A patellofemoral arthrodesis can be regarded safe and also very
effective in the relief of pain in extreme patella alta. LEVEL OF EVIDENCE:
Therapeutic studies, Level IV.
PMID- 25116347
TI - Rediscovering the patellofemoral joint.
PMID- 25116348
TI - Social networks and the communication of norms about prenatal care in rural
Mexico.
AB - Many normative beliefs are shared and learned through interpersonal
communication, yet research on norms typically focuses on their effects rather
than the communication that shapes them. This study focused on interpersonal
communication during pregnancy to uncover (a) the nature of pregnancy-related
communication and (b) normative information transmitted through such
communication. Results from interviews with pregnant women living in rural Mexico
revealed limited social networks; often, only a woman's mother or the baby's
father were consulted about prenatal care decisions. However, women also
indicated that communication with others during pregnancy provided important
normative information regarding prenatal care. First, most referents believed
that women should receive prenatal care (injunctive norm), which was
conceptualized by participants as biomedical, nonmedical, or a blend of both.
Second, family members often received prenatal care, whereas friends did not
(descriptive norms). These findings highlight the key role of personal and social
networks in shaping personal pregnancy-related beliefs and behaviors.
PMID- 25116349
TI - Parity and short-term estradiol treatment utilizes similar cellular mechanisms to
confer protection against breast cancer.
AB - BACKGROUND: Protective effect of early pregnancy and short-term estrogen
treatment (STET), against breast cancer is well established. The underlying
mechanisms are not well understood. In this study, we compared the mammary gland
cellular microenvironment influenced/induced by parity and STET alongside age
matched controls. METHODS: Parous, STET, and control rats were injected with N
methyl-N-nitrosourea at 15 weeks and monitored for the development of mammary
cancer. A subset of 4 rats were killed five weeks post carcinogen treatment and
mammary gland samples were isolated and subjected to molecular analysis. RESULTS:
Our results demonstrated a reduction in cell survival, extracellular matrix
associated proliferation, hormonal and growth factor receptor pathways in the
experimental groups compared to control rats. Moreover, concomitant reductions in
the EMT markers along with cell migration regulators were also observed in parous
and STET groups. Hormonal receptor such as GHR, PR, ERalpha and growth factor
receptors IGFR, EGFR and erbB2 were down regulated in the treatment groups.
Further analysis revealed that parity and STET drastically reduced the
expression, activation of JAK2 and nuclear localization of STATs. CONCLUSION:
Parity and STET by targeting major cell signaling pathways involved in cell
survival, cell migration and cell death reduces the mammary tumor promoting
environment.
PMID- 25116350
TI - Up-regulation of P21 inhibits TRAIL-mediated extrinsic apoptosis, contributing
resistance to SAHA in acute myeloid leukemia cells.
AB - BACKGROUND/AIM: P21, a multifunctional cell cycle-regulatory molecule, regulates
apoptotic cell death. In this study we examined the effect of altered p21
expression on the sensitivity of acute myeloid leukemia cells in response to HDAC
inhibitor SAHA treatment and investigated the underlying mechanism. METHODS:
Stably transfected HL60 cell lines were established in RPMI-1640 with
supplementation of G-418. Cell viability was measured by MTT assay. Western blot
was applied to assess the protein expression levels of target genes. Cell
apoptosis was monitored by AnnexinV-PE/7AAD assay. RESULTS: We showed HL60 cells
that that didn't up-regulate p21 expression were more sensitive to SAHA-mediated
apoptosis than NB4 and U937 cells that had increased p21 level. Enforced
expression of p21 in HL60 cells reduced sensitivity to SAHA and blocked TRAIL
mediated apoptosis. Conversely, p21 silencing in NB4 cells enhanced SAHA-mediated
apoptosis and lethality. Finally, we found that combined treatment with SAHA and
rapamycin down-regulated p21 and enhanced apoptosis in AML cells. CONCLUSION: We
conclude that up-regulated p21 expression mediates resistance to SAHA via
inhibition of TRAIL apoptotic pathway. P21 may serve as a candidate biomarker to
predict responsiveness or resistance to SAHA-based therapy in AML patients. In
addition, rapamycin may be an effective agent to override p21-mediated resistance
to SAHA in AML patients.
PMID- 25116352
TI - Induction of myocardial PDCD4 in coronary microembolization-related cardiac
dysfunction: evidence from a large-animal study.
AB - BACKGROUND/AIMS: Coronary microembolization (CME) has been linked to myocardial
inflammation and apoptosis. This study aims to investigate the role of the
apoptotic protein PDCD4 in the myocardium after CME in minipigs. METHODS: Seventy
Bama minipigs were randomized into four groups: control, CME, CME plus PDCD4
siRNA and CME plus control siRNA. CME was induced by injecting polyethylene
microspheres into the left anterior descending artery. Cardiac function was
evaluated. HE and HBFP staining were used to observe the degree of infarction.
Western blotting and qPCR were used to evaluate the expression of PDCD4, TNF
alpha and caspase-3. The measurements were performed at 0, 3, 6, 9, 12 and 24 h
after CME modeling in the CME and control groups. RESULTS: Cardiac function in
the CME group was significantly decreased compared with the control group
(P<0.05) and the expression of PDCD4 and TNF-alpha increased significantly
(P<0.05). However, the infarct area did not differ between the CME and control
groups at any time point (P>0.05). Furthermore, PDCD4-siRNA improved cardiac
function and reduced PDCD4 and TNF-alpha expression compared with the CME plus
control siRNA group at 9 h after modeling (P < 0.05), while the caspase-3 level
was not different between the two groups. CONCLUSION: PDCD4 induction may be
involved in CME-related cardiac dysfunction, and PDCD4 inhibition via siRNA may
attenuate the cardiac impairment and be used as a treatment strategy for CME.
PMID- 25116353
TI - Decreased MiR-200a/141 suppress cell migration and proliferation by targeting
PTEN in Hirschsprung's disease.
AB - BACKGROUND/AIMS: Hirschsprung's disease (HSCR) is a genetic disorder of neural
crest development. In this study, we investigated whether and how miR-200a and
miR-141, belonging to miR-200 family, were involved in the pathogenesis of HSCR.
METHODS: Quantitative real time PCR and Western blot were used to detect the
levels of miRNA, mRNAs, and proteins in colon tissues from 88 HSCR patients and
75 controls. The direct regulation of specific mRNA by miRNAs was validated by
dual-luciferase reporter assay and RNA interference in cell lines. Transwell
assays, CCK8 assay, and flow cytometry were inplemented to measure viability and
activities of human 293T and SH-SY5Y cells, respectively. RESULTS: Aberrant
suppression of miR-200a was observed in colon tissues of HSCR patients. A
decreased level of miR-200a and miR-141 correlated with increased levels of PTEN
mRNA and protein. The Dual-Luciferase reporter gene assay demonstrated that miR
200a and miR-141 binded directly to 3'UTR of PTEN and resulting in the inhibition
of PTEN. The reductions in miR-200a and miR-141 inhibited migration and
proliferation of 293T and SH-SY5Y cells through up-regulating the expression of
PTEN. Moreover, knocking-down of PTEN rescued the extent of suppressed cell
migration and proliferation induced by miR-200a and miR-141. CONCLUSIONS: The miR
200 family may play a crucial role in the pathogenesis of HSCR by co-regulating
PTEN.
PMID- 25116351
TI - Kruppel -like factor 8 is a stress-responsive transcription factor that regulates
expression of HuR.
AB - BACKGROUND/AIMS: HuR is an RNA-binding protein that regulates the post
transcriptional life of thousands of cellular mRNAs and promotes cell survival.
HuR is expressed as two mRNA transcripts that are differentially regulated by
cell stress. The goal of this study is to define factors that promote
transcription of the longer alternate form. METHODS: Effects of transcription
factors on HuR expression were determined by inhibition or overexpression of
these factors followed by competitive RT-PCR, gel mobility shift, and chromatin
immunoprecipitation. Transcription factor expression patterns were identified
through competitive RT-PCR and Western analysis. Stress responses were assayed in
thapsigargin-treated proximal tubule cells and in ischemic rat kidney. RESULTS: A
previously described NF-kappaB site and a newly identified Sp/KLF factor binding
site were shown to be important for transcription of the long HuR mRNA. KLF8, but
not Sp1, was shown to bind this site and increase HuR mRNA levels. Cellular
stress in cultured or native proximal tubule cells resulted in a rapid decrease
of KLF8 levels that paralleled those of the long HuR mRNA variant. CONCLUSIONS:
These results demonstrate that KLF8 can participate in regulating expression of
alternate forms of HuR mRNA along with NF-kappaB and other factors, depending on
cellular contexts.
PMID- 25116354
TI - Sex hormones regulate hepatic fetuin expression in male and female rats.
AB - BACKGROUND: To date, there are limited studies on the sex-specific relationship
between fetuins (Ft-A and Ft-B) and metabolic diseases. Our recent proteomic
study has shown that fetuins may play sex-dependent roles in obesity and
diabetes. In the present study, we investigated the expression of hepatic fetuins
with respect to the effects of sex hormones both in vivo and in vitro. METHODS &
RESULTS: A sex hormone-treated rat model was established in order to study the
effects of sex hormones on hepatic fetuin expression. Animal experiments revealed
that 17beta-estradiol (E2)- and dihydrotestosterone (DHT)-treated rats showed
opposite effects in terms of body weight gain in both genders. Interestingly, Ft
A and Ft-B were sex-dependently expressed in the livers of rats, responding to
different regulatory modes of sex hormone receptors (ERalpha, ERbeta, and AR). To
validate in vivo data, rat normal liver cells were treated with E2 or DHT at
different concentrations, and similar expression patterns as those in the animal
based experiments were confirmed. We found that these changes were mediated via
sex hormone receptors using antagonist experiments. CONCLUSION: The results of
the present study indicate that sex hormones induce gender-dimorphic expression
of hepatic fetuins directly via sex hormone receptors. To the best of our
knowledge, this is the first approach to address the effects of sex hormones on
hepatic fetuin expression.
PMID- 25116355
TI - OPN polymorphism is associated with the susceptibility to cervical spondylotic
myelopathy and its outcome after anterior cervical corpectomy and fusion.
AB - BACKGROUND: Osteopontin (OPN) is reportedly involved in bone desorption,
formation and ectopic calcification. We sought to investigate the role of OPN
gene polymorphism in the susceptibility to Cervical spondylotic myelopathy (CSM)
and in predicting the outcome anterior cervical corpectomy and fusion (ACF).
METHODS: A total of 187 patients diagnosed with CSM and 233 sex and age matched
healthy controls were enrolled in this study. All CSM patients received ACF and
were followed up for 24 months. The polymorphisms of OPN gene at 3 loci, namely,
156 G>GG, -443 C>T and -66T>G were determined. RESULTS: The -66T>G genotype was
significantly different between CSM patients and controls. Compared to the -66TT
carriers, the -66GG genotype carriers had a higher risk for developing CSM
(adjusted Odd Ratio=2.58, adjusted P=0.001). In contrast, the genotype
distributions of the -156G/GG and -443C/T loci were not significantly different
between the CSM and control groups. OPN gene polymorphism did not determine the
pre-operative severity of CSM patients, but the -66T>G genotype was significantly
associated with the clinical outcome of CSM after ACF treatment. The -66T>G did
not affect the serum OPN level, but affect the local expressions of OPN and a
serious of key inflammatory factors in the intervertebral disc samples.
CONCLUSION: Our study shows the OPN -66T>G genetic polymorphism contributes to
patients' susceptibility to CSM and could be indicative of the outcome of ACF
surgery.
PMID- 25116356
TI - Dysregulation of the glutamine transporter Slc38a3 (SNAT3) and ammoniagenic
enzymes in obese, glucose-intolerant mice.
AB - BACKGROUND/AIMS: Uric acid nephrolithiasis is prevalent among patients with type
2 diabetes and metabolic syndrome; it is correlated with an acidic urine and
lower urinary ammonium excretion and is likely associated with insulin
resistance. Insulin stimulates ammoniagenesis in renal cell lines via increased
phosphate-dependent glutaminase (PDG) activity and glutamine metabolism. Ammonium
excretion into the proximal tubule is mediated at least in part by the Na(+)/H(+)
exchanger NHE3 and in the collecting duct involving the Rhesus protein RhCG. Here
we tested, whether obesity and insulin resistance in a diet-induced mouse model
could contribute to deranged ammonium excretion. METHODS: Obesity was induced by
diet in mice and the impact on key molecules of proximal tubular ammoniagenesis
and urinary acid excretion tested. RESULTS: Diet-induced obesity was confirmed by
pathological intraperitoneal glucose tolerance tests (IPGTT). Three groups of
mice were compared: control mice; obese, glucose-intolerant with abnormal IPGTT
(O-GI); or moderate weight with normal IPGTT (Non-Responders, NR). Basal urinary
ammonium excretion did not differ among groups. However, acid loading increased
urinary ammonium excretion in all groups, but to a lesser extent in the O-GI
group. SNAT3 mRNA expression was enhanced in both obese groups. PDG expression
was elevated only in acid-loaded O-GI mice, whereas PEPCK was enhanced in both O
GI and NR groups given NH4CI. NHE activity in the brush border membrane of the
proximal tubule was strongly reduced in the O-GI group whereas RhCG expression
was similar. CONCLUSION: In sum, obesity and glucose intolerance impairs renal
ammonium excretion in response to NH4CI feeding most likely through reduced NHE
activity. The stimulation of SNAT3 and ammoniagenic enzyme expression may be
compensatory but futile.
PMID- 25116357
TI - GLP-2 suppresses LPS-induced inflammation in macrophages by inhibiting ERK
phosphorylation and NF-kappaB activation.
AB - BACKGROUND/AIMS: GLP-2 has been shown to exert anti-inflammatory effects, but the
underlying molecular mechanisms remained undefined. As macrophages are important
in the development and maintenance of inflammation, we investigated whether
exogenous GLP-2 modulates the expression of pro-inflammatory proteins in LPS
stimulated murine peritoneal macrophages. METHODS: Macrophages were pretreated
with various concentrations of GLP-2 for 1 h and then stimulated with LPS. The
effects on pro-inflammatory enzymes (iNOS and COX-2), and pro-inflammatory
cytokines (TNF-alpha, IL-1beta and IL-6) were analysed by Western blotting, ELISA
and qRT-PCR. We also examined whether NF-kappaB or MAPK signaling was involved in
the effects of GLP-2. RESULTS: In macrophages, GLP-2 blunted the effect of LPS on
protein and mRNA expression levels of iNOS, COX-2, TNF-alpha, IL-1beta and IL-6.
Pre-incubation of macrophages with GLP-2 also blunted LPS-induced IkappaB-alpha
degradation, IkappaB-alpha phosphorylation and NF-kappaB translocation. In the
presence of GLP-2, the effect of LPS treatment on ERK phosphorylation was also
profoundly blunted. GLP-2 did, however, not significantly modify the effects of
LPS on p38 and JNK activities. CONCLUSIONS: These findings demonstrate that in
LPS primed macrophages, GLP-2 reduced pro-inflammatory enzymes and cytokine
production via mechanisms involving the suppression of NF-kappaB activity and ERK
phosphorylation.
PMID- 25116358
TI - Resveratrol suppresses oxidised low-density lipoprotein-induced macrophage
apoptosis through inhibition of intracellular reactive oxygen species generation,
LOX-1, and the p38 MAPK pathway.
AB - BACKGROUND/AIM: Resveratrol (RSV) may have therapeutic potential for various
diseases. Here we investigated the effect of RSV on oxidised low-density
lipoprotein- (ox-LDL) induced apoptosis in RAW264.7 macrophages. METHODS:
Apoptosis of macrophages following incubation with ox-LDL (with or without RSV
pre-treatment) was detected by flow cytometry. Western blotting was used to
assess the protein expression of Bax, Bcl-2, and caspase-3 as well as ox-LDL
receptor 1 (LOX-1) and p38 mitogen-activated protein kinase (MAPK)
phosphorylation. Reactive oxygen species (ROS) generation was evaluated by 2', 7'
dichlorofluorescein diacetate, and JC-1 probe was used to determine the
mitochondrial transmembrane potential of cells. RESULTS: Ox-LDL significantly
reduced viability and increased the rate of apoptosis (P < 0.05) in RAW264.7
cells. However, pre-treatment with RSV resulted in a remarkable decrease in this
apoptotic effect. Moreover, ox-LDL caused the up-regulation of Bax and the down
regulation of Bcl-2, as well as the activation of caspase-3. Expression of LOX-1,
phosphorylation of p38 MAPK, and intracellular ROS production also increased
after ox-LDL stimulation. Strikingly, these effects were abolished by pre
treatment of cells with RSV. CONCLUSION: RSV suppresses ox-LDL-induced macrophage
apoptosis. These beneficial effects might be exerted through inhibition of ROS
generation, LOX-1, and the p38 MAPK signalling pathway.
PMID- 25116359
TI - Key residues responsible for enhancement of catalytic efficiency of Thermomyces
lanuginosus lipase Lip revealed by complementary protein engineering strategy.
AB - The variant Lip-T (S88T/A99N/V116D) of lipase Lip from Thermomyces lanuginosus
has been proved to be a potential biocatalyst for kinetic resolution of 2
carboxyethyl-3-cyano-5-methylhexanoic acid ethyl ester (CNDE) to produce valuable
chiral intermediate of Pregabalin. In this study, random, site-directed and site
saturation mutagenesis were performed to further enhance the activity of Lip-T,
and the key residues responsible for catalytic efficiency were revealed. A mutant
S63L/D232A with improved activity toward CNDE was obtained after screening of
approximately 2500 clones from random-mutant libraries. Site-directed mutagenesis
at site 63 and 232 demonstrated that the single-point mutants S63L and D232A
showed opposite effect on activity. S63L exhibited a significant improvement on
activity, whereas D232A exerted a slight inhibitory effect. Then a mutant S63M
with a 4.5-fold higher catalytic efficiency than Lip-T was obtained by site
saturation mutagenesis. Structural changes resulting from the mutations were
analyzed and the mechanisms responsible for the enhanced activity were discussed.
Moreover, the engineered lipase catalyzed enantioselective hydrolysis of CNDE at
a very high substrate loading (765 g/l). As only 5% (w/v) resting cells were
used, the bioprocess is much more cost-effective than Pfizer's process using 8%
(w/v) commercially available lipase Lipolase((r)). These results provide not only
new insights into lipase structure-function relationships but also a novel robust
biocatalyst for the production of Pregabalin.
PMID- 25116360
TI - An electrochemical genosensor for Salmonella typhi on gold nanoparticles
mercaptosilane modified screen printed electrode.
AB - In this work, we fabricated a system of integrated self-assembled layer of
organosilane 3-mercaptopropyltrimethoxy silane (MPTS) on the screen printed
electrode (SPE) and electrochemically deposited gold nanoparticle for Salmonella
typhi detection employing Vi gene as a molecular marker. Thiolated DNA probe was
immobilized on a gold nanoparticle (AuNP) modified SPE for DNA hybridization
assay using methylene blue as redox (electroactive) hybridization indicator, and
signal was monitored by differential pulse voltammetry (DPV) method. The modified
SPE was characterized by cyclic voltammetry (CV), electrochemical impedance
spectroscopy (EIS), and atomic force microscopy (AFM) method. The DNA biosensor
showed excellent performances with high sensitivity and good selectivity. The
current response was linear with the target sequence concentrations ranging from
1.0 * 10(-11) to 0.5 * 10(-8)M and the detection limit was found to be 50 (+/-
2.1)pM. The DNA biosensor showed good discrimination ability to the one-base, two
base and three-base mismatched sequences. The fabricated genosensor could also be
regenerated easily and reused for three to four times for further hybridization
studies.
PMID- 25116361
TI - In situ near infrared spectroscopy monitoring of cyprosin production by
recombinant Saccharomyces cerevisiae strains.
AB - Near infrared (NIR) spectroscopy was used to in situ monitoring the cultivation
of two recombinant Saccharomyces cerevisiae strains producing heterologous
cyprosin B. NIR spectroscopy is a fast and non-destructive technique, that by
being based on overtones and combinations of molecular vibrations requires
chemometrics tools, such as partial least squares (PLS) regression models, to
extract quantitative information concerning the variables of interest from the
spectral data. In the present work, good PLS calibration models based on specific
regions of the NIR spectral data were built for estimating the critical variables
of the cyprosin production process: biomass concentration, cyprosin activity,
cyprosin specific activity, the carbon sources glucose and galactose
concentration and the by-products acetic acid and ethanol concentration. The PLS
models developed are valid for both recombinant S. cerevisiae strains, presenting
distinct cyprosin production capacities, and therefore can be used, not only for
the real-time control of both processes, but also in optimization protocols. The
PLS model for biomass yielded a R(2)=0.98 and a RMSEP=0.46 g dcw l(-1),
representing an error of 4% for a calibration range between 0.44 and 13.75 g dcw
l(-1). A R(2)=0.94 and a RMSEP=167 Um l(-1) were obtained for the cyprosin
activity, corresponding to an error of 6.7% of the experimental data range (0
2509 Um l(-1)), whereas a R(2)=0.93 and RMSEP=672 U mg(-1) were obtained for the
cyprosin specific activity, corresponding to an error of 7% of the experimental
data range (0-11,690 Um g(-1)). For the carbon sources glucose and galactose, a
R(2)=0.96 and a RMSECV of 1.26 and 0.55 g l(-1), respectively, were obtained,
showing high predictive capabilities within the range of 0-20 g l(-1). For the
metabolites resulting from the cell growth, the PLS model for acetate was
characterized by a R(2)=0.92 and a RMSEP=0.06 g l (-1), which corresponds to a
6.1% error within the range of 0.41-1.23 g l(-1); for the ethanol, a high
accuracy PLS model with a R(2)=0.97 and a RMSEP=1.08 g l(-1) was obtained,
representing an error of 9% within the range of 0.18-21.76 g l(-1). The present
study shows that it is possible the in situ monitoring and prediction of the
critical variables of the recombinant cyprosin B production process by NIR
spectroscopy, which can be applied in process control in real-time and in
optimization protocols. From the above, NIR spectroscopy appears as a valuable
analytical tool for online monitoring of cultivation processes, in a fast,
accurate and reproducible operation mode.
PMID- 25116362
TI - Targeted genome correction by a single adenoviral vector simultaneously carrying
an inducible zinc finger nuclease and a donor template.
AB - Zinc finger nuclease (ZFN) technology, which can be used to induce targeted
genome correction in the presence of a DNA donor template, is becoming an
attractive strategy for treating monogenic diseases. This strategy requires
efficient delivery of ZFN and donor template into cells, ideally, in a single
viral vector to achieve efficient genome editing and to avoid unwanted
mutagenesis. In this study, we successfully produced a single adenoviral (Ad)
vector with high titer that carried a ZFN expression cassette and a donor
template simultaneously. We then demonstrated that this single Ad system could
mediate efficient site-specific genome correction in vitro and ex vivo. The gene
correction efficiency of the single Ad was significantly higher than that of the
double Ad system. This novel vector will be a promising ZFN and donor delivery
system for treatment of monogenic diseases.
PMID- 25116365
TI - Depositional characteristics of atmospheric polybrominated diphenyl ethers on
tree barks.
AB - OBJECTIVES: This study was conducted to determine the depositional
characteristics of several tree barks, including Ginkgo (Ginkgo biloba), Pine
(Pinus densiflora), Platanus (Platanus), and Metasequoia (Metasequoia
glyptostroboides). These were used as passive air sampler (PAS) of atmospheric
polybrominated diphenyl ethers (PBDEs). METHODS: Tree barks were sampled from the
same site. PBDEs were analyzed by highresolution gas chromatography/high
resolution mass spectrometer, and the lipid content was measured using the
gravimetric method by n-hexane extraction. RESULTS: Gingko contained the highest
lipid content (7.82 mg/g dry), whereas pine (4.85 mg/g dry), Platanus (3.61 mg/g
dry), and Metasequoia (0.97 mg/g dry) had relatively lower content. The highest
total PBDEs concentration was observed in Metasequoia (83,159.0 pg/g dry),
followed by Ginkgo (53,538.4 pg/g dry), Pine (20,266.4 pg/g dry), and Platanus
(12,572.0 pg/g dry). There were poor correlations between lipid content and total
PBDE concentrations in tree barks (R(2)=0.1011, p =0.682). Among the PBDE
congeners, BDE 206, 207 and 209 were highly brominated PBDEs that are sorbed to
particulates in ambient air, which accounted for 90.5% (84.3-95.6%) of the
concentration and were therefore identified as the main PBDE congener. The
concentrations of particulate PBDEs deposited on tree barks were dependent on
morphological characteristics such as surface area or roughness of barks.
CONCLUSIONS: Therefore, when using the tree barks as the PAS of the atmospheric
PBDEs, samples belonging to same tree species should be collected to reduce
errors and to obtain reliable data.
PMID- 25116363
TI - Voluntary pressing and releasing actions induce different senses of time:
evidence from event-related brain responses.
AB - The timing intervals initiated by voluntary pressing actions are subjectively
compressed compared with those initiated by voluntary releasing actions. Event
related potentials (ERPs) were employed in the present study to uncover the
temporal mechanisms underlying this temporal illusion. The results revealed that
the mean amplitude of the P1 component over the frontal-central recording sites,
but not the P2 component, was larger in the voluntary pressing condition than in
the voluntary releasing condition at the time perception stage. In the fronto
central region, increases in oscillatory activities of delta-theta frequency
range (1-7 Hz) were found in the voluntary pressing condition, which corresponded
with the emergence of the P1 peak. In addition, the P1 amplitude was negatively
related to the corresponding reported time length at the single-trial level.
These results are discussed in terms of the functional role of the response
locked P1 in the time perception stage.
PMID- 25116364
TI - NUCKS1, a novel Tat coactivator, plays a crucial role in HIV-1 replication by
increasing Tat-mediated viral transcription on the HIV-1 LTR promoter.
AB - BACKGROUND: Human immunodeficiency virus-1 (HIV-1) Tat protein plays an essential
role in HIV gene transcription from the HIV-1 long terminal repeat (LTR) and
replication. Transcriptional activity of Tat is modulated by several host
factors, but the mechanism responsible for Tat regulation by host factors is not
understood fully. RESULTS: Using a yeast two-hybrid screening system, we
identified Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1
(NUCKS1) as a novel Tat-interacting partner. Here, we report its function as a
positive regulator of Tat. In a coimmunoprecipitation assay, HIV-1 Tat interacted
sufficiently with both endogenous and ectopically expressed NUCKS1. In a reporter
assay, ectopic expression of NUCKS1 significantly increased Tat-mediated
transcription of the HIV-1 LTR, whereas knockdown of NUCKS1 by small interfering
RNA diminished Tat-mediated transcription of the HIV-1 LTR. We also investigated
which mechanism contributes to NUCKS1-mediated Tat activation. In a chromatin
immunoprecipitation assay (ChIP), knockdown of NUCKS1 interrupted the
accumulation of Tat in the transactivation-responsive (TAR) region on the LTR,
which then led to suppression of viral replication. However, NUCKS1 expression
did not increase Tat nuclear localization and interaction with Cyclin T1.
Interestingly, the NUCKS1 expression level was lower in latently HIV-1-infected
cells than in uninfected parent cells. Besides, expression level of NUCKS1 was
markedly induced, which then facilitated HIV-1 reactivation in latently infected
cells. CONCLUSION: Taken together, our data demonstrate clearly that NUCKS1 is a
novel Tat coactivator that is required for Tat-mediated HIV-1 transcription and
replication, and that it may contribute to HIV-1 reactivation in latently HIV-1
infected cells.
PMID- 25116367
TI - Spatial analysis of PM10 and cardiovascular mortality in the Seoul metropolitan
area.
AB - OBJECTIVES: Numerous studies have revealed the adverse health effects of acute
and chronic exposure to particulate matter less than 10 MUm in aerodynamic
diameter (PM10). The aim of the present study was to examine the spatial
distribution of PM10 concentrations and cardiovascular mortality and to
investigate the spatial correlation between PM10 and cardiovascular mortality
using spatial scan statistic (SaTScan) and a regression model. METHODS: From 2008
to 2010, the spatial distribution of PM10 in the Seoul metropolitan area was
examined via kriging. In addition, a group of cardiovascular mortality cases was
analyzed using SaTScan-based cluster exploration. Geographically weighted
regression (GWR) was applied to investigate the correlation between PM10
concentrations and cardiovascular mortality. RESULTS: An examination of the
regional distribution of the cardiovascular mortality was higher in provincial
districts (gu) belonging to Incheon and the northern part of Gyeonggido than in
other regions. In a comparison of PM10 concentrations and mortality cluster (MC)
regions, all those belonging to MC 1 and MC 2 were found to belong to particulate
matter (PM) 1 and PM 2 with high concentrations of air pollutants. In addition,
the GWR showed that PM10 has a statistically significant relation to
cardiovascular mortality. CONCLUSIONS: To investigate the relation between air
pollution and health impact, spatial analyses can be utilized based on kriging,
cluster exploration, and GWR for a more systematic and quantitative analysis. It
has been proven that cardiovascular mortality is spatially related to the
concentration of PM10.
PMID- 25116366
TI - Skin corrosion and irritation test of sunscreen nanoparticles using reconstructed
3D human skin model.
AB - OBJECTIVES: Effects of nanoparticles including zinc oxide nanoparticles, titanium
oxide nanoparticles, and their mixtures on skin corrosion and irritation were
investigated by using in vitro 3D human skin models (KeraSkin ((TM)) ) and the
results were compared to those of an in vivo animal test. METHODS: Skin models
were incubated with nanoparticles for a definite time period and cell viability
was measured by the 3-(4, 5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide
method. Skin corrosion and irritation were identified by the decreased viability
based on the pre-determined threshold. RESULTS: Cell viability after exposure to
nanomaterial was not decreased to the pre-determined threshold level, which was
15% after 60 minutes exposure in corrosion test and 50% after 45 minutes exposure
in the irritation test. IL-1alpha release and histopathological findings support
the results of cell viability test. In vivo test using rabbits also showed non
corrosive and non-irritant results. CONCLUSIONS: The findings provide the
evidence that zinc oxide nanoparticles, titanium oxide nanoparticles and their
mixture are 'non corrosive' and 'non-irritant' to the human skin by a globally
harmonized classification system. In vivo test using animals can be replaced by
an alternative in vitro test.
PMID- 25116371
TI - Summary health statistics for the u.s. Population: national health interview
survey, 2011.
AB - Objectives-This report presents both age-adjusted and unadjusted health
statistics from the 2011 National Health Interview Survey (NHIS) for the civilian
noninstitutionalized population of the United States. Estimates are disaggregated
by sex, age, race, Hispanic origin, education, family income, poverty status,
health insurance coverage (where appropriate), place of residence, and region of
residence. The topics covered are respondent-assessed health status, limitations
in activities, special education or early intervention services, injury and
poisoning episodes, health care access and utilization, and health insurance
coverage. Data Source-NHIS is a household, multistage probability sample survey
conducted annually by interviewers of the U.S. Census Bureau for the Centers for
Disease Control and Prevention's National Center for Health Statistics. In 2011,
household interviews were completed for 101,875 persons living in 39,509
households, reflecting a household response rate of 82.0%. Selected Highlights
Nearly 7 in 10 persons were in excellent or very good health in 2011. About 40
million persons (13%) were limited in their usual activities due to one or more
chronic health conditions. About 5 million persons (2%) required the help of
another person with activities of daily living, and about 10 million persons (4%)
required the help of another person with instrumental activities of daily living.
About 7% of children received special education or early intervention services.
Among persons under age 65, about 45 million (17%) did not have any health
insurance coverage. The most common reason for lacking health insurance was cost,
followed by a change in employment.
PMID- 25116370
TI - Marine biotechnologies and synthetic biology, new issues for a fair and equitable
profit-sharing commercial use.
AB - The sea will be a source of economic development in the next years. Today the
research works in marine biotechnologies supply new products and processes. The
introduction in the laboratories of a new technology, synthesis biology, is going
to increase the possibilities of creation of new products. Exploitation of
product stemming from marine biodiversity has to be made with regard to various
rights among which industrial property law, maritime law and the Convention on
BioDiversity. All participants involved in the promotion of research in marine
biotechnology must address the fair and equitable sharing of any commercial
exploitation. Carrying out work involving synthetic biology has increased the
number of unanswered questions about how operators should manage in order to
avoid any threat of being sued for infringements of IP rights or for alleged bio
piracy. This paper, by no means exhaustive in the field, analyzes some of the
issues raised on the modification to the landscape in marine biotechnology by the
advent of synthetic biology. Such issues indicate how important the collaboration
between researchers, industrialists, lawyers is for allowing proper use of marine
biotech.
PMID- 25116369
TI - Older adults recently started on psychotropic medication: where are the symptoms?
AB - OBJECTIVE: The objective of this study is to understand the characteristics of
older adults on newly prescribed psychotropic medication with minimal psychiatric
symptoms. METHODS: Naturalistic cohort study of non-institutionalized older
adults in Pennsylvania participating in the Pharmaceutical Assistance Contract
for the Elderly. Persons newly prescribed antidepressant or anxiolytic
monotherapy or combination therapy were contacted for clinical assessment by a
telephone-based behavioral health service. The initial assessment included
standardized mental health screening instruments and scales including the Blessed
Orientation-Memory-Concentration test, Patient Health Questionnaire-9,
Generalized Anxiety Disorder-7, and Medical Outcomes Survey (SF-12). In addition,
patients were asked for their understanding of the prescription indication.
RESULTS: Of the 254 participants who met minimal symptom criteria (Patient Health
Questionnaire-9 < 5 and Generalized Anxiety Disorder-7 < 5), women comprised
slightly more of the anxiolytic compared with antidepressant monotherapy group
(88.9% vs. 76.7%, p = 0.04). The most common self-reported reason for
prescription of an antidepressant or anxiolytic was depression or anxiety,
respectively, despite near-absence of these symptoms on clinical assessment.
Comparing monotherapy to combination therapy groups, those with combination
therapy were more likely to report a history of depression (12.6% vs. 1.8%, p <
0.001) and also report depression as the reason for the prescription (40.2% vs.
21.0%, p < 0.01). CONCLUSIONS: In this sample of older adults on new psychotropic
medication with minimal psychiatric symptoms, there are few patient
characteristics that distinguish those on antidepressant versus anxiolytic
monotherapy or those on monotherapy versus combination therapy. While quality of
care in late-life mental health has focused on improving detection and treatment,
there should be further attention to low-symptom patients potentially receiving
inappropriate pharmacotherapy.
PMID- 25116372
TI - Treatment outcome of Chinese children with anaplastic large cell lymphoma by
using a modified B-NHL-BFM-90 protocol.
AB - Pediatric anaplastic large cell lymphoma (ALCL) has rarely been reported in
Chinese pediatric patients. This study evaluated the clinical characteristics and
treatment outcome of Chinese pediatric patients with ALCL. Between October 2002
and October 2012, 39 untreated pediatric patients with ALCL were enrolled at a
single institution. The patients were stratified into three groups (R1, R2, and
R3) based on the stage of the disease, clinical risk factors, and
chemotherapeutic response, and received different intensive chemotherapy regimens
based on a modified B-NHL-BFM-90 protocol. Of the 39 patients, 22 were boys, and
17 were girls, with a median age at diagnosis of 10 years (range 2-16 years),
91.2% were anaplastic lymphoma kinase (ALK)-positive. The patient groups R1, R2,
and R3 accounted for 12.8%, 30.4%, and 56.4% of the total, respectively. 87.2% of
patients were stage III/IV. At a median follow-up period of 52 months (range 15
136 months), seven patients relapsed and three patients died of their disease.
The 5-year event-free survival for all patients was 81.4% +/- 6.4%, with 100%,
83.3% +/- 10% and 75.3% +/- 9.8% for groups R1, R2, and R3, respectively. The
overall survival for all patients was 92.2% +/- 4.3%. Our study demonstrates that
a risk-stratified treatment with a modified B-NHL-BFM-90 protocol is efficacious
for Chinese children with ALCL.
PMID- 25116375
TI - AgNb7O18: an ergodic relaxor ferroelectric.
AB - AgNb7O18 is a relaxor ferroelectric with a Burns temperature of ~490 K and an
incipient transition to the nonergodic state. The short-range structure is shown
by convergent-beam electron diffraction to have the polar space group Im2m, but
refinements against powder X-ray diffraction find the long-range structure to
have the centrosymmetric space group Immm. Relaxor behavior in AgNb7O18 appears
to originate from the partial occupation of large interstices by Ag(+) cations.
Both cations and oxygen anions are displaced away from zones where NbO6 octahedra
are edge-sharing.
PMID- 25116373
TI - Endothelial amine oxidase AOC3 transiently contributes to adaptive immune
responses in the airways.
AB - Amine oxidase, copper containing 3 (AOC3, also known as vascular adhesion protein
1 (VAP-1)) is an endothelial adhesion molecule that contributes to the
extravasation of neutrophils, macrophages, and lymphocytes to sites of
inflammation. However, the role of AOC3/VAP-1 in allergic responses remains
unknown. Here, we studied eosinophil and CD4+ T-cell recruitment to the airways
using AOC3/VAP-1-deficient mice. In an OVA-triggered asthma model, AOC3/VAP-1
slightly contributed to the accumulation of leukocytes in lungs in an age
dependent manner. We then established a new model to kinetically measure
recruitment of OVA-specific CD4+ T cells to different airway immune compartments
during the priming and effector phases of an adaptive immune response. The
results showed that in the absence of AOC3/VAP-1, recruitment of antigen-specific
CD4+ T cells to draining bronchial lymph nodes is reduced by 89% on day 3 after
tracheal allergen exposure, but this difference was not observed on day 6. The
dispersal of effector cells to lung and tracheal mucosa is AOC3/VAP-1
independent. Thus, in allergic airway reactions, AOC3/VAP-1 transiently
contributes to the antigen-specific, CD4+ T-cell traffic to secondary lymphatic
tissues, but not to airway mucosa or lung parenchyma. Our results suggest a
largely redundant function for AOC3/VAP-1 in allergic inflammatory responses of
the airways.
PMID- 25116376
TI - Assisted reproduction for postmenopausal women.
AB - With increasing longevity, an ageing population and advances in assisted
reproductive technologies (ART), a greater number of women are deciding to have a
child and become a mother in their later years. With this social and demographic
change, an important social and ethical debate has emerged over whether single
and/or married postmenopausal women should have access to ARTs. The aim of this
paper is to address this question and review critically the arguments that have
been advanced to support or oppose the use of ART by older women. The arguments
presented consider the consequences for the individual, the family and wider
society. They cover the potential physical and emotional harm to the older woman,
the possible impact on the welfare and wellbeing of the future child, and the
impact on the norms, values, customs and traditions of society. After reviewing
the evidence, and weighing the opposing arguments, this paper concludes that
there is no moral justification for a restriction on the use of ART by
postmenopausal women. Allowing access to ART for postmenopausal women is an
extension of reproductive autonomy and procreative rights in an age where the
promotion of agency, autonomy, individual choice and human rights is paramount.
PMID- 25116378
TI - Homologies and homeotic transformation of the theropod 'semilunate' carpal.
AB - The homology of the 'semilunate' carpal, an important structure linking non-avian
and avian dinosaurs, has been controversial. Here we describe the morphology of
some theropod wrists, demonstrating that the 'semilunate' carpal is not formed by
the same carpal elements in all theropods possessing this feature and that the
involvement of the lateralmost distal carpal in forming the 'semilunate' carpal
of birds is an inheritance from their non-avian theropod ancestors. Optimization
of relevant morphological features indicates that these features evolved in an
incremental way and the 'semilunate' structure underwent a lateral shift in
position during theropod evolution, possibly as a result of selection for
foldable wings in birds and their close theropod relatives. We propose that
homeotic transformation was involved in the evolution of the 'semilunate' carpal.
In combination with developmental data on avian wing digits, this suggests that
homeosis played a significant role in theropod hand evolution in general.
PMID- 25116379
TI - Oxygen etching of thick MoS2 films.
AB - Oxygen annealing of thick MoS2 films results in randomly oriented and
controllable triangular etched shapes, forming pits with uniform etching angles.
These etching morphologies differ across the sample based on the defect sites
situated on the basal plane surface, forming numerous features in different bulk
sample thicknesses.
PMID- 25116377
TI - Programmable nanoscaffolds that control ligand display to a G-protein-coupled
receptor in membranes to allow dissection of multivalent effects.
AB - A programmable ligand display system can be used to dissect the multivalent
effects of ligand binding to a membrane receptor. An antagonist of the A2A
adenosine receptor, a G-protein-coupled receptor that is a drug target for
neurodegenerative conditions, was displayed in 35 different multivalent
configurations, and binding to A2A was determined. A theoretical model based on
statistical mechanics was developed to interpret the binding data, suggesting the
importance of receptor dimers. Using this model, extended multivalent
arrangements of ligands were constructed with progressive improvements in binding
to A2A. The results highlight the ability to use a highly controllable
multivalent approach to determine optimal ligand valency and spacing that can be
subsequently optimized for binding to a membrane receptor. Models explaining the
multivalent binding data are also presented.
PMID- 25116381
TI - An improved method for including upper size range plasmids in metamobilomes.
AB - Two recently developed isolation methods have shown promise when recovering pure
community plasmid DNA (metamobilomes/plasmidomes), which is useful in conducting
culture-independent investigations into plasmid ecology. However, both methods
employ multiple displacement amplification (MDA) to ensure suitable quantities of
plasmid DNA for high-throughput sequencing. This study demonstrates that MDA
greatly favors smaller circular DNA elements (<10 Kbp), which, in turn, leads to
stark underrepresentation of upper size range plasmids (>10 Kbp). Throughout the
study, we used two model plasmids, a 4.4 Kbp cloning vector (pBR322), and a 56
Kbp conjugative plasmid (pKJK10), to represent lower- and upper plasmid size
ranges, respectively. Subjecting a mixture of these plasmids to the overall
isolation protocol revealed a 34-fold over-amplification of pBR322 after MDA. To
address this bias, we propose the addition of an electroelution step that
separates different plasmid size ranges prior to MDA in order to reduce size
dependent competition during incubation. Subsequent analyses of metamobilome data
from wastewater spiked with the model plasmids showed in silica recovery of
pKJK10 to be very poor with the established method and a 1,300-fold
overrepresentation of pBR322. Conversely, complete recovery of pKJK10 was enabled
with the new modified protocol although considerable care must be taken during
electroelution to minimize cross-contamination between samples. For further
validation, non-spiked wastewater metamobilomes were mapped to more than 2,500
known plasmid genomes. This displayed an overall recovery of plasmids well into
the upper size range (median size: 30 kilobases) with the modified protocol.
Analysis of de novo assembled metamobilome data also suggested distinctly better
recovery of larger plasmids, as gene functions associated with these plasmids,
such as conjugation, was exclusively encoded in the data output generated through
the modified protocol. Thus, with the suggested modification, access to a large
uncharacterized pool of accessory elements that reside on medium-to-large
plasmids has been improved.
PMID- 25116382
TI - Heat-killed probiotic bacteria differentially regulate colonic epithelial cell
production of human beta-defensin-2: dependence on inflammatory cytokines.
AB - The inducible antimicrobial peptide human beta-defensin-2 (hBD-2) stimulated by
pro-inflammatory cytokines and bacterial products is essential to antipathogen
responses of gut epithelial cells. Commensal and probiotic bacteria can augment
such mucosal defences. Probiotic use in the treatment of inflammatory bowel
disease, however, may have adverse effects, boosting inflammatory responses. The
aim of this investigation was to determine the effect of selected probiotic
strains on hBD-2 production by epithelial cells induced by pathologically
relevant pro-inflammatory cytokines and the role of cytokine modulators in
controlling hBD-2. Caco-2 colonic intestinal epithelial cells were pre-incubated
with heat-killed probiotics, i.e. Lactobacillus casei strain Shirota (LcS) or
Lactobacillus fermentum strain MS15 (LF), followed by stimulation of hBD-2 by
interleukin (IL)-1beta and tumour necrosis factor alpha (TNF-alpha) in the
absence or presence of exogenous IL-10 or anti-IL-10 neutralising antibody.
Cytokines and hBD-2 mRNA and protein were analysed by real-time quantitative
polymerase chain reaction and enzyme-linked immunosorbent assay. LcS augmented IL
1beta-induced hBD-2, whereas LF enhanced TNF-alpha- and suppressed IL-1beta
induced hBD-2. LF enhanced TNF-alpha-induced TNF-alpha and suppressed IL-10,
whereas augmented IL-1beta-induced IL-10. LcS upregulated IL-1beta-induced TNF
alpha mRNA and suppressed IL-10. Endogenous IL-10 differentially regulated hBD-2;
neutralisation of IL-10 augmented TNF-alpha- and suppressed IL-1beta-induced hBD
2. Exogenous IL-10, however, suppressed both TNF-alpha- and IL-1beta-induced hBD
2; LcS partially rescued suppression in TNF-alpha- and IL-1beta-stimulation,
whereas LF further suppressed IL-1beta-induced hBD-2. It can be concluded that
probiotic strains differentially regulate hBD-2 mRNA expression and protein
secretion, modulation being dictated by inflammatory stimulus and resulting
cytokine environment.
PMID- 25116383
TI - Testing the proclaimed affordances of online support groups in a nationally
representative sample of adults seeking mental health assistance.
AB - In this study, explanations for why people turn to the Internet for social
support are tested using a nationally representative sample of adults who sought
mental health support through a traditional treatment outlet, an in-person
support group, or an online support group. Results indicate that the more adults
report having social stigma concerns, the more likely they are to seek support
online instead of help from an in-person support group or traditional treatment.
Likewise, as the reported number of logistical barriers to mental health
treatment increases, a corresponding increase occurs in the odds of adults
seeking online support instead of traditional treatment. These findings as well
as estimates of demographic variation in the use of online support are discussed.
PMID- 25116380
TI - Acetylation-dependent regulation of essential iPS-inducing factors: a regulatory
crossroad for pluripotency and tumorigenesis.
AB - Induced pluripotent stem (iPS) cells can be generated from somatic cells by
coexpression of four transcription factors: Sox2, Oct4, Klf4, and c-Myc. However,
the low efficiency in generating iPS cells and the tendency of tumorigenesis
hinder the therapeutic applications for iPS cells in treatment of human diseases.
To this end, it remains largely unknown how the iPS process is subjected to
regulation by upstream signaling pathway(s). Here, we report that Akt regulates
the iPS process by modulating posttranslational modifications of these iPS
factors in both direct and indirect manners. Specifically, Akt directly
phosphorylates Oct4 to modulate the Oct4/Sox2 heterodimer formation. Furthermore,
Akt either facilitates the p300-mediated acetylation of Oct4, Sox2, and Klf4, or
stabilizes Klf4 by inactivating GSK3, thus indirectly modulating stemness. As
tumorigenesis shares possible common features and mechanisms with iPS, our study
suggests that Akt inhibition might serve as a cancer therapeutic approach to
target cancer stem cells.
PMID- 25116384
TI - Vitamin D insufficiency over 5 years is associated with increased fracture risk
an observational cohort study of elderly women.
AB - This study of elderly Swedish women investigated the association between chronic
vitamin D insufficiency and osteoporotic fractures occurring between ages 80-90.
The incidence and risk of hip and major osteoporotic fractures was significantly
higher in elderly women with low vitamin D levels maintained over 5 years.
INTRODUCTION: Vitamin D insufficiency among the elderly is common; however,
relatively little is known about the effects of long-term hypovitaminosis D on
fracture. We investigated sequential assessment of serum 25(OH)D at age 75 and 80
to determine if continuously low 25(OH)D levels are associated with increased 10
year fracture incidence. METHODS: One thousand forty-four Swedish women from the
population-based OPRA cohort, all 75 years old, attended at baseline (BL); 715
attended at 5 years. S-25(OH)D was available in 987 and 640, respectively and
categorized as: <50 (Low), 50-75 (Intermediate), and >75 nmol/L (High). Incident
fracture data was collected with maximum follow-up to 90 years of age. RESULTS:
Hip fracture incidence between age 80-85 was higher in women who had low 25(OH)D
at both baseline and 5 years (22.2 % (Low) vs. 6.6 % (High); p = 0.003). Between
age 80-90, hip fracture incidence was more than double that of women in the high
category (27.9 vs. 12.3 %; p = 0.006). Within 5-years, 50 % of women in the
continuously low group compared to 34 % in the continuously high 25(OH)D group
had an osteoporotic fracture (p = 0.004) while 10-year incidence was higher
compared to the intermediate (p = 0.020) but not the high category (p = 0.053).
The 10-year relative risk of hip fracture was almost three times higher and
osteoporotic fracture risk almost doubled for women in the lowest 25(OH)D
category compared to the high category (HR 2.7 and 1.7; p = 0.003 and 0.023,
respectively). CONCLUSION: In these elderly women, 25(OH)D insufficiency over 5
years was associated with increased 10-year risk of hip and major osteoporotic
fractures.
PMID- 25116385
TI - Vitamin D: is evidence of absence, absence of evidence?
PMID- 25116386
TI - Response to letter to editor.
PMID- 25116388
TI - Construction of four low-dimensional NIR-luminescence-tunable Yb(III) complexes.
AB - Four low-dimensional ytterbium(iii)-organic compounds through hydrothermal
reactions of quinoline-2,3-dicarboxylic acid (2,3-H2qldc) and oxalic acid (H2ox)
with Yb2O3, namely, [Yb(2,3-qldc)(ox)1/2(H2O)3.(H2O)4]n (1), [Yb(2,3
qldc)(ox)1/2(H2O)2.(H2O)2]n (2), [Yb(2,3-Hqldc)(ox)(H2O)2.(H2O)]n (3) and [Yb(2,3
Hqldc)(ox)(H2O).(H2O)2]n (4), were first synthesized and characterized by
elemental analysis (EA), infrared spectroscopy (IR), thermogravimetric analysis
(TG), and single-crystal X-ray diffraction. When the reactant ratio of 2,3-H2qldc
: H2ox : Yb2O3 is 2 : 1 : 1, 1-D chain-like complex 1 with three coordinated
water molecules around the Yb(iii) ion was obtained in mixed solvents of H2O and
CH3OH (v : v = 10 : 1) at 70 degrees C, and with the increase of temperature to
100 degrees C, the same reactants gave 2-D 6(3) topological layer-like complex 2
with two coordinated water molecules in the coordination sphere of the Yb(iii)
ion. However, when the reactant ratio was changed to 1 : 1 : 1, two 2-D 6(3)
topological layer-like complexes 3 (70 degrees C) and 4 (100 degrees C) were
obtained at different temperatures, in which the coordination water molecules in
3 and 4 are two and one, respectively. Obviously, these results reveal that the
reaction temperature and reactant ratios play critical roles in the structural
direction of these low-dimensional compounds. Interestingly, with the gradual
loss of coordination water molecules to the Yb(iii) ion, the near infrared (NIR)
emission of four Yb(iii)-based compounds 1-4 can be gradually strengthened with
increasing order of 1 < 3 < 2 < 4, indicating that these ytterbium(iii) complexes
have tunable near infrared luminescence.
PMID- 25116387
TI - Using RNA-seq and targeted nucleases to identify mechanisms of drug resistance in
acute myeloid leukemia.
AB - The evolution from microarrays to transcriptome deep-sequencing (RNA-seq) and
from RNA interference to gene knockouts using Clustered Regularly Interspaced
Short Palindromic Repeats (CRISPRs) and Transcription Activator-Like Effector
Nucleases (TALENs) has provided a new experimental partnership for identifying
and quantifying the effects of gene changes on drug resistance. Here we describe
the results from deep-sequencing of RNA derived from two cytarabine (Ara-C)
resistance acute myeloid leukemia (AML) cell lines, and present CRISPR and TALEN
based methods for accomplishing complete gene knockout (KO) in AML cells. We
found protein modifying loss-of-function mutations in Dck in both Ara-C resistant
cell lines. CRISPR and TALEN-based KO of Dck dramatically increased the IC50 of
Ara-C and introduction of a DCK overexpression vector into Dck KO clones resulted
in a significant increase in Ara-C sensitivity. This effort demonstrates the
power of using transcriptome analysis and CRISPR/TALEN-based KOs to identify and
verify genes associated with drug resistance.
PMID- 25116389
TI - Sequences outside that of residues 93-102 of 3A protein can contribute to the
ability of foot-and-mouth disease virus (FMDV) to replicate in bovine-derived
cells.
AB - Foot-and-mouth disease (FMD) is a highly contagious and economically devastating
disease of cloven-hoofed animals. During 2010 and 2011, there was an epidemic of
the Mya-98 lineage of the Southeast Asia (SEA) topotype in East Asia, including
China. Changes in the FMDV 3A protein have been previously reported to be
associated with the inability of FMDV to grow in bovine cells and cause disease
in cattle. In this paper, we report the generation of a full-length infectious
cDNA clone of FMDV O/SEA/Mya-98 strain O/GZSB/2011 for the first time along with
two genetically modified viruses with deletion at positions 93-102 and 133-143 in
3A based on the established infectious clone. All the recombinant viruses grew
well and displayed growth properties and plaque phenotypes similar to those of
the parental virus in baby hamster kidney (BHK-21) cells, porcine kidney (PK-15)
cells, and primary fetal porcine kidney (FPK) cells. While the recombinant
viruses rvGZSB and rvSBDelta133-143 exhibited similar growth properties and
plaque phenotypes with the parental virus in primary fetal bovine kidney (FBK)
cells, the recombinant virus rvSBDelta93-102, containing deletion at positions 93
102 in 3A, grew at a slower rate and had a smaller plaque size phenotype in FBK
cells than that of the parental virus. Therefore, the results suggest that the
deletion at positions 93-102 of 3A protein does not affect FMDV replication
efficiency in BHK-21, PK-15 and FPK cells, but affects virus replication
efficiency in FBK cells, although, cannot alone account for the inability to
replicate in bovine cells.
PMID- 25116390
TI - Activation of PI3K/Akt pathway limits JNK-mediated apoptosis during EV71
infection.
AB - Apoptosis is frequently induced to inhibit virus replication during infection of
Enterovirus 71 (EV71). On the contrary, anti-apoptotic pathway, such as PI3K/Akt
pathway, is simultaneously exploited by EV71 to accomplish the viral life cycle.
The relationship by which EV71-induced apoptosis and PI3K/Akt signaling pathway
remains to be elucidated. In this study, we demonstrated that EV71 infection
altered Bax conformation and triggered its redistribution from the cytosol to
mitochondria in RD cells. Subsequently, cytochrome c was released from
mitochondria to cytosol. We also found that c-Jun NH2-terminal kinase (JNK) was
activated during EV71 infection. The JNK specific inhibitor significantly
inhibited Bax activation and cytochrome c release, suggesting that EV71-induced
apoptosis was involved into a JNK-dependent manner. Meanwhile, EV71-induced Akt
phosphorylation involved a PI3K-dependent mechanism. Inhibition of the PI3K/Akt
pathway enhanced JNK phosphorylation and the JNK-mediated apoptosis upon EV71
infection. Moreover, PI3K/Akt pathway phosphorylated apoptosis signal-regulating
kinase 1 (ASK1) and negatively regulated the ASK1 activity. Knockdown of ASK1
significantly decreased JNK phosphorylation, which implied that ASK1
phosphorylation by Akt inhibited ASK1-mediated JNK activation. Collectively,
these data reveal that activation of the PI3K/Akt pathway limits JNK-mediated
apoptosis by phosphorylating and inactivating ASK1 during EV71 infection.
PMID- 25116391
TI - The SARS Coronavirus 3a protein binds calcium in its cytoplasmic domain.
AB - The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is a positive
stranded RNA virus with ~30kb genome. Among all open reading frames (orfs) of
this virus, the orf3a is the largest, and encodes a protein of 274 amino acids,
named as 3a protein. Sequence analysis suggests that the orf3a aligned to one
calcium pump present in Plasmodium falciparum and the enzyme glutamine synthetase
found in Leptospira interrogans. This sequence similarity was found to be limited
only to amino acid residues 209-264 which form the cytoplasmic domain of the
orf3a. Furthermore, this region was predicted to be involved in the calcium
binding. Owing to this hypothesis, we were driven to establish its calcium
binding property in vitro. Here, we expressed and purified the cytoplasmic domain
of the 3a protein, called Cyto3a, as a recombinant His-tagged protein in the E.
coli. The calcium binding nature was established by performing various staining
methods such as ruthenium red and stains-all. (45)Ca overlay method was also done
to further support the data. Since the 3a protein forms ion channels, we were
interested to see any conformational changes occurring in the Cyot3a upon calcium
binding, using fluorescence spectroscopy and circular dichroism. These studies
clearly indicate a significant change in the conformation of the Cyto3a protein
after binding with calcium. Our results strongly suggest that the cytoplasmic
domain of the 3a protein of SARS-CoV binds calcium in vitro, causing a change in
protein conformation.
PMID- 25116392
TI - Porcine epidemic diarrhea virus infects and replicates in porcine alveolar
macrophages.
AB - Porcine epidemic diarrhea virus (PEDV) is a causative agent of porcine epidemic
diarrhea; consequently, the small intestine was believed to be its only target
organ. In this study, we found that PEDV infected not only the small intestines,
but also the respiratory tract. Infection and replication of PEDV in the
respiratory tract from naturally PEDV-infected piglets were examined by reverse
transcription polymerase chain reaction, immunohistochemistry, and virus re
isolation. Our observations were confirmed by experimental inoculation, and we
found that PEDV infection in the respiratory tract was specifically associated
with alveolar macrophages in the lung. Vero cell-adapted PEDV was able to
replicate in both primary alveolar macrophages and continuous porcine alveolar
macrophage cells. Sequencing analysis of the spike (S) glycoprotein revealed that
mutations in S might be a potential determinant of auxiliary targets for PEDV.
The discovery that PEDV infects and replicates in alveolar macrophages provides
new insights into its pathogenesis.
PMID- 25116396
TI - Nursing and the new biology: towards a realist, anti-reductionist approach to
nursing knowledge.
AB - As a system of knowledge, nursing has utilized a range of subjects and
reconstituted them to reflect the thinking and practice of health care. Often
drawn to a holistic model, nursing finds it difficult to resist the reductionist
tendencies in biological and medical thinking. In this paper I will propose a
relational approach to knowledge that is able to address this issue. The paper
argues that biology is not characterized by one stable theory but is often a
contentious topic and employs philosophically diverse models in its scientific
research. Biology need not be seen as a reductionist science, but reductionism is
nonetheless an important current within biological thinking. These reductionist
currents can undermine nursing knowledge in four main ways. Firstly, that the
conclusions drawn from reductionism go far beyond their data based on an approach
that prioritizes biological explanations and eliminates others. Secondly, that
the methods employed by biologists are sometimes weak, and the limitations are
insufficiently acknowledged. Thirdly, that the assumptions that drive the
research agenda are problematic, and finally that uncritical application of these
ideas can be potentially disastrous for nursing practice. These issues are
explored through an examination of the problems reductionism poses for the issue
of gender, mental health, and altruism. I then propose an approach based on
critical realism that adopts an anti-reductionist philosophy that utilizes the
conceptual tools of emergence and a relational ontology.
PMID- 25116395
TI - Solution and high-pressure NMR studies of the structure, dynamics, and stability
of the cross-reactive allergenic cod parvalbumin Gad m 1.
AB - Beta-parvalbumins from different fish species have been identified as the main
elicitors of IgE-mediated reactions in fish-allergic individuals. Here, we report
for the first time the NMR determination of the structure and dynamics of the
major Atlantic cod (Gadus morhua) allergen Gad m 1 and compare them with other
known parvalbumins. Although the Gad m 1 structure and accessibility of putative
IgE epitopes are similar to parvalbumins in mackerel and carp, the charge
distribution at the putative epitopes is different. The determination of the Gad
m 1 structure contributes to a better understanding of cross-reactivity among
fish parvalbumins. In addition, the high-pressure NMR and temperature variation
experiments revealed the important contribution of the AB motif and other regions
to the protein folding. This structural information could assist the future
identification of hot spots for targeted mutations to develop hypoallergenic
Ca(2+) -free forms for potential use in immunotherapy.
PMID- 25116393
TI - Overexpression of Gremlin-1 in patients with Loeys-Dietz syndrome: implications
on pathophysiology and early disease detection.
AB - BACKGROUNDS: The Loeys-Dietz syndrome (LDS) is an inherited connective tissue
disorder caused by mutations in the transforming growth factor beta (TGF-beta)
receptors TGFBR1 or TGFBR2. Most patients with LDS develop severe aortic
aneurysms resulting in early need of surgical intervention. In order to gain
further insight into the pathophysiology of the disorder, we investigated
circulating outgrowth endothelial cells (OEC) from the peripheral blood of LDS
patients from a cohort of 23 patients including 6 patients with novel TGF-beta
receptor mutations. METHODS AND RESULTS: We performed gene expression profiling
of OECs using microarray analysis followed by quantitative PCR for verification
of gene expression. Compared to OECs of age- and sex-matched healthy controls,
OECs isolated from three LDS patients displayed altered expression of several
genes belonging to the TGF-beta pathway, especially those affecting bone
morphogenic protein (BMP) signalling including BMP2, BMP4 and BMPR1A. Gene
expression of BMP antagonist Gremlin-1 (GREM1) showed the most prominent up
regulation. This increase was confirmed at the protein level by immunoblotting of
LDS-OECs. In immunohistochemistry, abundant Gremlin-1 protein expression could be
verified in endothelial cells as well as smooth muscle cells within the arterial
media. Furthermore, Gremlin-1 plasma levels of LDS patients were significantly
elevated compared to healthy control subjects. CONCLUSIONS: These findings open
new avenues in the understanding of the pathogenesis of Loeys-Dietz syndrome and
the development of new diagnostic serological methods for early disease
detection.
PMID- 25116394
TI - Hypoxia preconditioned mesenchymal stem cells prevent cardiac fibroblast
activation and collagen production via leptin.
AB - AIMS: Activation of cardiac fibroblasts into myofibroblasts constitutes a key
step in cardiac remodeling after myocardial infarction (MI), due to interstitial
fibrosis. Mesenchymal stem cells (MSCs) have been shown to improve post-MI
remodeling an effect that is enhanced by hypoxia preconditioning (HPC). Leptin
has been shown to promote cardiac fibrosis. The expression of leptin is
significantly increased in MSCs after HPC but it is unknown whether leptin
contributes to MSC therapy or the fibrosis process. The objective of this study
was to determine whether leptin secreted from MSCs modulates cardiac fibrosis.
METHODS: Cardiac fibroblast (CF) activation was induced by hypoxia (0.5% O2). The
effects of MSCs on fibroblast activation were analyzed by co-culturing MSCs with
CFs, and detecting the expression of alpha-SMA, SM22alpha, and collagen IalphaI
in CFs by western blot, immunofluorescence and Sirius red staining. In vivo MSCs
antifibrotic effects on left ventricular remodeling were investigated using an
acute MI model involving permanent ligation of the left anterior descending
coronary artery. RESULTS: Co-cultured MSCs decreased fibroblast activation and
HPC enhanced the effects. Leptin deficit MSCs from Ob/Ob mice did not decrease
fibroblast activation. Consistent with this, H-MSCs significantly inhibited
cardiac fibrosis after MI and mediated decreased expression of TGF-beta/Smad2 and
MRTF-A in CFs. These effects were again absent in leptin-deficient MSCs.
CONCLUSION: Our data demonstrate that activation of cardiac fibroblast was
inhibited by MSCs in a manner that was leptin-dependent. The mechanism may
involve blocking TGF-beta/Smad2 and MRTF-A signal pathways.
PMID- 25116397
TI - A potential biomarker in sports-related concussion: brain functional connectivity
alteration of the default-mode network measured with longitudinal resting-state
fMRI over thirty days.
AB - Current diagnosis and monitoring of sports-related concussion rely on clinical
signs and symptoms, and balance, vestibular, and neuropsychological examinations.
Conventional brain imaging often does not reveal abnormalities. We sought to
assess if the longitudinal change of functional and structural connectivity of
the default-mode network (DMN) can serve as a potential biomarker. Eight
concussed Division I collegiate football student-athletes in season (one
participated twice) and 11 control subjects participated in this study. ImPACT
(Immediate Post-Concussion Assessment and Cognitive Testing) was administered
over the course of recovery. High-resolution three dimensional T1-weighted, T2*
weighted diffusion-tensor images and resting-state functional magnetic resonance
imaging (rs-fMRI) scans were collected from each subject within 24 h, 7+/-1 d and
30+/-1 d after concussion. Both network based and whole-brain based functional
correlation analyses on DMN were performed. ImPACT findings demonstrated
significant cognitive impairment across multiple categories and a significant
increase of symptom severity on Day 1 following a concussion but full recovery by
6.0+/-2.4 d. While the structural connectivity within DMN and gross anatomy
appeared unchanged, a significantly reduced functional connectivity within DMN
from Day 1 to Day 7 was found in the concussed group in this small pilot study.
This reduction was seen in eight of our nine concussion cases. Compared with the
control group, there appears a general trend of increased DMN functional
connectivity on Day 1, a significant drop on Day 7, and partial recovery on Day
30. The results of this pilot study suggest that the functional connectivity of
DMN measured with longitudinal rs-fMRI can serve as a potential biomarker to
monitor the dynamically changing brain function after sports-related concussion,
even in patients who have shown clinical improvement.
PMID- 25116398
TI - Schistosoma mansoni antigen detects Schistosoma mekongi infection.
AB - Northern Cambodia and Southern Laos are highly endemic for Schistosoma mekongi.
However, there is currently no immunological assay available that is specific for
this form of schistosomiasis. We have validated Schistosoma mansoni antigens to
detect S. mekongi-directed antibodies in human sera collected from a highly S.
mekongi endemic region in Laos. On two consecutive days stool samples of 234
individuals were analyzed by Kato-Katz for presence of S. mekongi eggs and the
results were correlated with serology. A sensitivity of 94.5% was calculated for
a combination of ELISA and indirect fluorescence assay (IFA) as compared to the
detection of S. mekongi eggs in stool samples as gold standard. The results
demonstrate that S. mansoni antigens can be used for the diagnosis of S. mekongi
infections.
PMID- 25116399
TI - A systematic review on the quality of life benefits after percutaneous coronary
intervention in the elderly.
AB - AIMS: Percutaneous coronary intervention (PCI) is being increasingly performed on
elderly patients with acceptable peri-procedural outcomes and long-term survival.
We aim to systematically review the health-related quality of life (HRQOL)
following PCI in the elderly which is an important measure of procedural success.
METHODS: A systematic review of clinical studies before September 2012 was
performed to identify HRQOL in the elderly after PCI. Strict inclusion and
exclusion criteria were applied. Quality appraisal of each study was also
performed using pre-defined criteria. HRQOL results were synthesised through a
narrative review with full tabulation of results of all included studies.
RESULTS: Elderly patients have significant improvements in cardiovascular well
being. Early HRQOL appears improved from baseline, but recovery in physical
health may be slower than in younger patients. HRQOL is comparable to an age
matched general population and younger patients undergoing PCI. Conservative
management is not able to offer the same HRQOL benefits. Coronary artery bypass
graft surgery may be superior to PCI in the very elderly. Significant
heterogeneity and bias exists. Lack of appropriate data precluded meta-analysis.
CONCLUSION: HRQOL after PCI in the elderly can improve for at least 1 year across
a broad range of health domains, and is comparable to an age-matched general
population and younger patients undergoing PCI. Given a limited number of
articles and patients included, more prospective studies are needed to better
identify the benefits for elderly patients.
PMID- 25116400
TI - Summary health statistics for u.s. Adults: national health interview survey,
2011.
AB - Objectives-This report presents health statistics from the 2011 National Health
Interview Survey (NHIS) for the civilian noninstitutionalized adult population,
classified by sex, age, race and Hispanic origin, education, family income,
poverty status, health insurance coverage, marital status, and place and region
of residence. Estimates (frequencies and percentages) are presented for selected
chronic conditions and mental health characteristics, functional limitations,
health status, health behaviors, health care access and utilization, and human
immunodeficiency virus testing. Percentages and percent distributions are
presented in both age-adjusted and unadjusted versions. Data Source-NHIS is a
household, multistage probability sample survey conducted annually by
interviewers of the U.S. Census Bureau for the Centers for Disease Control and
Prevention's National Center for Health Statistics. In 2011, data were collected
on 33,014 adults in the Sample Adult questionnaire. The conditional response rate
was 81.6%, and the final response rate was 66.3%. The health information for
adults in this report was obtained from one randomly selected adult per family.
In very rare instances where the sample adult was not able to respond for himself
or herself, a proxy was used. Highlights-In 2011, 61% of adults aged 18 and over
had excellent or very good health. Eleven percent of adults had been told by a
doctor or other health professional that they had heart disease, 24% had been
told on two or more visits that they had hypertension, 9% had been told that they
had diabetes, and 22% had been told that they had some form of arthritis,
rheumatoid arthritis, gout, lupus, or fibromyalgia. Nineteen percent of adults
were current smokers, and 21% were former smokers. Based on estimates of body
mass index, 34% of adults were overweight and 28% were obese.
PMID- 25116401
TI - Nilotinib in combination with carboplatin and paclitaxel is a candidate for
ovarian cancer treatment.
AB - PURPOSE: Nilotinib is a selective tyrosine kinase inhibitor of c-Kit, Abl and
platelet-derived growth factor receptor-alpha/beta. To evaluate nilotinib's
potential use as a treatment of human ovarian cancer, we tested nilotinib's
preclinical activity in ovarian cancer cell lines with different tyrosine kinase
expression patterns. METHODS: The effects of nilotinib on ovarian cancer cell
growth were studied alone and in combination with carboplatin and paclitaxel.
Proapoptotic and antimigratory effects were examined using TUNEL and migration
assays. RESULTS: Nilotinib alone and in combination with carboplatin and
paclitaxel significantly inhibited cell growth in PDGFR-alpha-positive ovarian
cancer cell lines. The combination of nilotinib with carboplatin and paclitaxel
showed synergistic effects on cell proliferation. Nilotinib treatment led to the
inhibition of cell migration alone and in combination with carboplatin and
paclitaxel. Apoptosis induction occurred in response to nilotinib that increased
in combination with carboplatin. CONCLUSIONS: Nilotinib may be a feasible
targeted therapy option for the treatment of ovarian cancer.
PMID- 25116402
TI - Unrelated CD3/CD19-depleted peripheral stem cell transplantation for Hurler
syndrome.
AB - For patients with mucopolysaccharidosis type IH (MPS1-H; Hurler syndrome), early
allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of
choice. One boy and one girl aged 20.5 and 22 months, respectively, with MPS1-H
received a conditioning regimen consisting of thiotepa, fludarabine, treosulfan,
and ATG. Grafts were peripheral blood stem cells from unrelated donors (10/12 and
11/11 matched), that were manipulated by CD3/CD19 depletion and contained 20.3
and 28.2 * 10(6) CD34+ cells/kg body weight, respectively. Both patients achieved
stable hematopoietic engraftment and stable donor chimerism. Neither acute or
chronic graft-versus-host disease (GVHD) nor other severe transplant-related
complications occurred. At a follow-up of 48 and 37 months, both patients are
alive and well with normal levels of alpha-L-iduronidase and have made major
neurodevelopmental progress. Treosulfan-based conditioning offers the advantage
of reduced toxicity; the use of unrelated CD3/CD19-depleted peripheral stem cell
grafts allows transfusion of high CD34+ cell numbers together with a "tailored"
number of CD3+ cells as well as engraftment facilitating cells in order to
achieve rapid hematopoietic engraftment while reducing the risk of graft
rejection and GVHD. This regimen might be an additional option when unrelated
donor HSCT is considered for a patient with MPS1-H.
PMID- 25116403
TI - Assisted reproductive technology--IVF treatment in Ireland: a study of couples
with successful outcomes.
AB - This article describes the experiences of twelve Irish couples who had successful
IVF treatment in Ireland. Irish Medical guidelines specify that IVF may only be
used when no other treatment is likely to be effective. This article is based on
data drawn from a longitudinal research study by Cotter (2009) which tells the
stories of 34 couples who sought fertility treatment. Initially, the women
assumed that they would become pregnant when they stopped using contraception. As
a couple, it was the 'right time' for them to have a child--they were ready,
socially and financially. For several months they were patient, hoping it would
happen naturally. With envy and some despair they watched as their friends had
babies. Infertility came as a shock to most of them. They were reluctant to talk
about it to anyone, and over time their anxieties were accompanied by feelings of
regret, stigma and social exclusion. They finally sought medical treatment. The
latter involved a series of diagnostic treatments, which eventually culminated in
IVF which offered them a final chance of having a 'child of their own'. While IVF
can be clinically assessed in terms of cycle success rates, their stories showed
treatment as a series of discoveries, as an extensive range of diagnostic tests
and procedures helped to reveal to them where their problems might lie. They
described their treatments as a series of sequential 'hurdles' that they had to
overcome, which further strengthened their resolve to try IVF. Much more
knowledgeable at that stage, they embraced IVF as a final challenge with single
minded dedication while drawing on all their psychological and biological
resources to promote a successful outcome. Of the 34 couples who took part in the
study, twelve got pregnant. Unfortunately, two children died shortly after birth
but eighteen babies survived (see Table I). The findings suggest that health
policy should raise awareness of infertility, and advise women to become aware of
it--just as in the past, when health policy addressed contraception. Increased
public knowledge would reduce the stigma attached to the inability to have a
baby. In the Irish case, infertility diagnosis should be reviewed with a view to
giving eligible couples earlier access to IVF.
PMID- 25116405
TI - Synthesis, structures, and solution dynamics of tetrasubstituted nine-atom
germanium deltahedral clusters.
AB - Reported are the rational synthesis, structures, and solution dynamics of three
tetrasubstituted and neutral Ge9-based deltahedral clusters [Ge9R3R'](0), where R
= Si(SiMe3)3 and R' = Et (1), Sn(n)Bu3 (2), or Tl (3). The first step of the
synthesis is a reaction of an acetonitrile suspension of the intermetallic
precursor compound K4Ge9 with {Si(SiMe3)3}Cl which produces the trisubstituted
monoanions [Ge9{Si(SiMe3)3}](-). A benzene suspension of the latter is then
reacted with Sn(n)Bu3Cl or TlCp to produce 2 and 3, respectively, while the same
acetonitrile solution is reacted with EtBr in order to produce 1. All three
structures can be viewed as tricapped trigonal prisms of Ge9 with the three
"hypersilyl" substituents, Si(SiMe3)3, exo-bonded to the capping atoms. The
fourth substituent in 1, the ethyl group, is exo-bonded to one of the six
available Ge atoms with the Ge-C bond positioned radially to the Ge9 core. In the
case of 2, on the other hand, the tin fragment is found above one of the
triangular bases of the prism interacting with one or more Ge atoms in three
crystallographically different molecules in the structure. Lastly, the Tl atom in
the structure of 3 is found capping a pseudosquare face between two hypersilyl
substituents. NMR spectroscopy indicates that all three compounds are dynamic at
room temperature. Variable-temperature studies suggest that the process in 1 and
2 is intramolecular while the process in 3 involves dissociation of the Tl(+) ion
from the molecule followed by association at the same or another equivalent
pseudosquare face of the molecule. Thus, the latter compound may be considered to
a large extent to be ionic as it is made of a thallium cation and a
trisubstituted cluster anion.
PMID- 25116406
TI - Cd(II)-MOF: adsorption, separation, and guest-dependent luminescence for
monohalobenzenes.
AB - A series of isostructural 2-fold interpenetrating 2D Cd(II)-MOFs, namely
G?CdL2(OTs)2 (G = THF (1), PhF (2), PhCl (3), PhBr (4), PhI (5), L = 1,2-bis[(3
(pyridin-4-yl)phenoxy]ethane, and OTs(-) = p-toluenesulfonate anion), have been
successfully synthesized from the flexible ethylene glycol ether-bridging ligand
L and Cd(OTs)2 in solution. The CdL2(OTs)2 framework contains squarelike nonpolar
channels, and the encapsulated guest molecules can be removed by heating (150
degrees C) to generate a guest-free host framework which is able to reversibly
adsorb monohalobenzenes PhX (X = F, Cl, Br, I) in the liquid phase under ambient
conditions without loss of framework integrity. Furthermore, it can effectively
separate these monohalobenzenes and exhibits a clear affinity for
monohalobenzenes according to the following order: PhI > PhBr > PhCl > PhF. In
addition, PhX?CdL2(OTs)2 exhibits guest-dependent luminescence properties.
PMID- 25116404
TI - IL-33 attenuates the development of experimental autoimmune uveitis.
AB - Interleukin-33 (IL-33) is associated with several important immune-mediated
disorders. However, its role in uveitis, an important eye inflammatory disease,
is unknown. Here, we investigated the function of IL-33 in the development of
experimental autoimmune uveitis (EAU). IL-33 and IL-33 receptor (ST2) were
expressed in murine retinal pigment epithelial (RPE) cells in culture, and IL-33
increased the expression of Il33 and Mcp1 mRNA in RPE cells. In situ, IL-33 was
highly expressed in the inner nuclear cells of the retina of naive mice, and its
expression was elevated in EAU mice. ST2-deficient mice developed exacerbated EAU
compared with WT mice, and administration of IL-33 to WT mice significantly
reduced EAU severity. The attenuated EAU in IL-33-treated mice was accompanied by
decreased frequency of IFN-gamma+ and IL-17(+) CD4+ T cells and reduced IFN-gamma
and IL-17 production but with increased frequency of IL-5(+) and IL-4(+) CD4 T
cells and IL-5 production in the draining lymph node and spleen. Macrophages from
the IL-33-treated mice show a significantly higher polarization toward an
alternatively activated macrophage phenotype. Our results therefore demonstrate
that the endogenous IL-33/ST2 pathway plays an important role in EAU, and suggest
that IL-33 represents a potential option for treatment of uveitis.
PMID- 25116408
TI - Symptomatic excyclotorsion following inferior transposition of both medial rectus
muscles in patients with bilateral trochlear nerve palsy.
AB - PURPOSE: To report the development of a large degree of excyclotorsion following
inferior transposition of the medial rectus muscles in 5 patients with bilateral
acquired trochlear nerve palsies that had previously undergone bilateral modified
Harada-Ito procedures. METHODS: The medical records of 5 patients who had
undergone Harada-Ito procedure for bilateral trochlear nerve palsy between 2002
and 2010 and medial rectus muscle infraplacement surgery between 2004 and 2012
were retrospectively reviewed. RESULTS: All 5 patients underwent a Fells-modified
Harada-Ito procedure. All remained symptomatic due to a V pattern (eso- or
exodeviation). Bilateral inferior transposition of the medial rectus muscles of
either half or full tendon width was performed to alleviate this residual
diplopia. The vertical transposition resulted in a symptomatic large degree of
excyclotorsion (mean of 20 degrees ), which required reversal of the procedure.
CONCLUSIONS: After inferior transposition of both medial rectus muscles in
patients with bilateral superior oblique palsy who previously had bilateral
modified Harada-Ito surgery, a large excyclotorsion (>20 degrees ) can occur.
This can be managed by reversing the medial rectus transposition procedure.
PMID- 25116407
TI - The newt reprograms mature RPE cells into a unique multipotent state for retinal
regeneration.
AB - The reprogramming of retinal pigment epithelium (RPE) cells in the adult newt
immediately after retinal injury is an area of active research for the study of
retinal disorders and regeneration. We demonstrate here that unlike
embryonic/larval retinal regeneration, adult newt RPE cells are not directly
reprogrammed into retinal stem/progenitor cells; instead, they are programmed
into a unique state of multipotency that is similar to the early optic vesicle
(embryo) but preserves certain adult characteristics. These cells then
differentiate into two populations from which the prospective-neural retina and
RPE layers are formed with the correct polarity. Furthermore, our findings
provide insight into the similarity between these unique multipotent cells in
newts and those implicated in retinal disorders, such as proliferative
vitreoretinopathy, in humans. These findings provide a foundation for biomedical
approaches that aim to induce retinal self-regeneration for the treatment of RPE
mediated retinal disorders.
PMID- 25116409
TI - Second to fourth digit ratio: a predictor of adult testicular volume.
AB - It has been suggested that second to fourth digit ratio (digit ratio) may
correlate with male reproductive system function or disorders. This hypothesis is
based on finding that the Hox genes control finger development and
differentiation of the genital bud during embryogenesis. Thus, we investigated
the association between digit ratio and adult testicular volume. A total of 172
Korean men (aged 20-69 years) hospitalized for urological surgery were
prospectively enrolled. Patients with conditions known to strongly influence
testicular volume were excluded. Before determining testicular volume, the
lengths of the second and fourth digits of the right hand were measured by a
single investigator using a digital vernier calliper. Using orchidometry, the
testes were measured by an experienced urologist who had no information about the
patient's digit ratio. To identify the independent predictive factors influencing
testicular volume, univariate and multivariate analyses were performed using
linear regression models. Age, height, serum testosterone and free testosterone
level were not correlated with testicular volume. Digit ratio, along with weight,
was significantly correlated with testicular volume (right testicular volume: r =
-0.185, p = 0.015; left testicular volume: r = -0.193, p = 0.011; total
testicular volume: r = -0.198, p = 0.009). Multivariate analysis using linear
regression models showed that only digit ratio was the independent factor to
predict all (right, left and total) testicular volumes (right testicular volume:
beta = -0.174, p = 0.023; left testicular volume: beta = -0.181, p = 0.017; total
testicular volume: beta = -0.185, p = 0.014). Our findings demonstrated that
digit ratio is negatively associated with adult testicular volume. This means
that men with a higher digit ratio may be more likely to have smaller testis
compared to those with a lower digit ratio.
PMID- 25116410
TI - A mechanistic study on SMOB-ADP1: an NADH:flavin oxidoreductase of the two
component styrene monooxygenase of Acinetobacter baylyi ADP1.
AB - Two styrene monooxygenase types, StyA/StyB and StyA1/StyA2B, have been described
each consisting of an epoxidase and a reductase. A gene fusion which led to the
chimeric reductase StyA2B and the occurrence in different phyla are major
differences. Identification of SMOA/SMOB-ADP1 of Acinetobacter baylyi ADP1 may
enlighten the gene fusion event since phylogenetic analysis indicated both
proteins to be more related to StyA2B than to StyA/StyB. SMOB-ADP1 is classified
like StyB and StyA2B as HpaC-like reductase. Substrate affinity and turnover
number of the homo-dimer SMOB-ADP1 were determined for NADH (24 uM, 64 s(-1)) and
FAD (4.4 uM, 56 s(-1)). SMOB-ADP1 catalysis follows a random sequential
mechanism, and FAD fluorescence is quenched upon binding to SMOB-ADP1 (K d = 1.8
uM), which clearly distinguishes that reductase from StyB of Pseudomonas. In
summary, this study confirmes made assumptions and provides phylogenetic and
biochemical data for the differentiation of styrene monooxygenase-related flavin
reductases.
PMID- 25116412
TI - The surface chemistry of metal-organic frameworks.
AB - Metal-organic frameworks (MOFs) have received particular attention over the last
20 years as a result of their attractive properties offering potential
applications in a number of areas. Typically, these characteristics are tuned by
functionalisation of the bulk of the MOF material itself. This Feature Article
focuses instead on modification of MOF particles at their surfaces only, which
can also offer control over the bulk properties of the material. The differing
surface modification techniques available to the synthetic chemist will be
discussed, with a focus on the effect of surface modification of MOFs on their
fundamental properties and application in adsorption, catalysis, drug delivery
and other areas.
PMID- 25116411
TI - Carbon partitioning to the terpenoid biosynthetic pathway enables heterologous
beta-phellandrene production in Escherichia coli cultures.
AB - Escherichia coli was used as a microbial system for the heterologous synthesis of
beta-phellandrene, a monoterpene of plant origin with several potential
commercial applications. Expression of Lavandula angustifolia beta-phellandrene
synthase (PHLS), alone or in combination with Picea abies geranyl-diphosphate
synthase in E. coli, resulted in no beta-phellandrene accumulation, in sharp
contrast to observations with PHLS-transformed cyanobacteria. Lack of beta
phellandrene biosynthesis in E. coli was attributed to the limited endogenous
carbon partitioning through the native 2-C-methylerythritol-4-phosphate (MEP)
pathway. Heterologous co-expression of the mevalonic acid pathway, enhancing
cellular carbon partitioning and flux toward the universal isoprenoid precursors,
isopentenyl-diphosphate and dimethylallyl-diphosphate, was required to confer
beta-phellandrene production. Differences in endogenous carbon flux toward the
synthesis of isoprenoids between photosynthetic (Synechocystis) and non
photosynthetic bacteria (E. coli) are discussed in terms of differences in the
regulation of carbon partitioning through the MEP biosynthetic pathway in the two
systems.
PMID- 25116413
TI - Cervical cancer prevention in Malawi: a qualitative study of women's
perspectives.
AB - Researchers posit that cervical cancer knowledge is central to participation in
prevention behaviors. However, of the many barriers to cervical cancer prevention
in low- and middle-income countries, cervical cancer knowledge remains severely
limited among communities at great risk for the disease. Malawi is one such
country where the burden of cervical cancer is considerably high. Formative
research targeting cervical cancer prevention is needed, particularly research
that explores ways to deliver cervical cancer information efficiently and
effectively to Malawian women. In this study, the authors aimed to garner
Malawian women's understanding of cervical cancer and to shed light on
preferences for health information delivery, including community health advocacy.
Qualitative, in-depth interviews were conducted with 30 Malawian women and
analyzed for recurring themes. In general, women had limited cervical cancer
knowledge, which supported misperceptions about the disease, including factors
pertaining to risk and prevention. Nonetheless, women reported that receiving
cervical cancer information from trusted sources would help promote preventive
behaviors. Women noted that they received most of their health information from
hospital personnel, but distance was a barrier. Women also expressed interest in
community health advocacy. Perspectives from Malawian women may be vital toward
informing efforts to increase cervical cancer knowledge and prevention.
PMID- 25116414
TI - Reassessing the improbability of a muscular crinoid stem.
AB - Muscular articulations in modern stalked crinoids are only present in the arms.
Although it has been suggested that certain coiled-stemmed fossil taxa may have
been functionally adapted to utilize muscles, evidence supporting this
interpretation is lacking. Here, we use cathodoluminescence and SEM to reveal the
skeletal microstructure of the enigmatic coiled-stemmed taxon Ammonicrinus
(Flexibilia). Based on the well-established link between skeletal microstructure
and the nature of infilling soft tissues in modern echinoderms, we reconstructed
the palaeoanatomy of the Middle Devonian ammonicrinids. We show that their median
columnals with elongated lateral columnal enclosure extensions (LCEE) have
stereom microstructure unexpectedly resembling that in the crinoid muscular arm
plates. In particular, large ligamentary facets, that are present on each side of
a transverse ridge, are mainly comprised of fine galleried stereom that is
indicative of the mutable collagenous tissues. In contrast, fine labyrinthic
stereom, commonly associated with muscles, is situated in the periphery on each
side of the surface of elongated LCEE. Our findings thus strongly suggest that
the muscles may have also been present in the stem of ammonicrinids. These
results reassess the previous hypotheses about evolution of muscles in crinoids
and provide new insights into the mode of life of Ammonicrinus.
PMID- 25116415
TI - A time course-dependent metastatic gene expression signature predicts outcome in
human metastatic melanomas.
AB - BACKGROUND: The prognosis of patients with metastatic melanomas is extremely
heterogeneous. Therefore, identifying high-risk subgroups by using innovative
prediction models would help to improve selection of appropriate management
options. METHODS: In this study, two datasets (GSE7929 and GSE7956) of mRNA
expression microarray in an animal melanoma model were normalized by frozen
Robust Multi-Array Analysis and then combined by the distance-weighted
discrimination method to identify time course-dependent metastasis-related gene
signatures by Biometric Research Branch-ArrayTools (BRB)-ArrayTools. Then two
datasets (GSE8401 and GSE19234) of clinical melanoma samples with relevant
clinical and survival data were used to validate the prognosis signature.
RESULTS: A novel 192-gene set that varies significantly in parallel with the
increasing of metastatic potentials was identified in the animal melanoma model.
Further, this gene signature was validated to correlate with poor prognosis of
human metastatic melanomas but not of primary melanomas in two independent
datasets. Furthermore, multivariate Cox proportional hazards regression analyses
demonstrated that the prognostic value of the 192-gene set is independent of the
TNM stage and has higher areas under the receiver operating characteristic curve
than stage information in both validation datasets. CONCLUSION: Our findings
suggest that a time course-dependent metastasis-related gene expression signature
is useful in predicting survival of malignant melanomas and might be useful in
informing treatment decisions for these patients.
PMID- 25116417
TI - Assessment of long-term prognosis at detection of early hepatocellular carcinoma
remains unsolved.
PMID- 25116416
TI - Physiological and brain activity after a combined cognitive behavioral treatment
plus video game therapy for emotional regulation in bulimia nervosa: a case
report.
AB - BACKGROUND: PlayMancer is a video game designed to increase emotional regulation
and reduce general impulsive behaviors, by training to decrease arousal and
improve decision-making and planning. We have previously demonstrated the
usefulness of PlayMancer in reducing impulsivity and improving emotional
regulation in bulimia nervosa (BN) patients. However, whether these improvements
are actually translated into brain changes remains unclear. OBJECTIVE: The aim of
this case study was to report on a 28-year-old Spanish woman with BN, and to
examine changes in physiological variables and brain activity after a combined
treatment of video game therapy (VGT) and cognitive behavioral therapy (CBT).
METHODS: Ten VGT sessions were carried out on a weekly basis. Anxiety,
physiological, and impulsivity measurements were recorded. The patient was
scanned in a 1.5-T magnetic resonance scanner, prior to and after the 10-week
VGT/CBT combined treatment, using two paradigms: (1) an emotional face-matching
task, and (2) a multi-source interference task (MSIT). RESULTS: Upon completing
the treatment, a decrease in average heart rate was observed. The functional
magnetic resonance imaging (fMRI) results indicated a post-treatment reduction in
reaction time along with high accuracy. The patient engaged areas typically
active in healthy controls, although the cluster extension of the active areas
decreased after the combined treatment. CONCLUSIONS: These results suggest a
global improvement in emotional regulation and impulsivity control after the VGT
therapy in BN, demonstrated by both physiological and neural changes. These
promising results suggest that a combined treatment of CBT and VGT might lead to
functional cerebral changes that ultimately translate into better cognitive and
emotional performances.
PMID- 25116418
TI - Severe methemoglobinemia due to ingestion of toxicants.
AB - BACKGROUND: Toxin-induced methemoglobinemia is seen in poisoning with oxidizing
agents. We report the clinical features and outcome of patients admitted with
severe methemoglobinemia due to intentional ingestion of toxicants. METHODS: In
this observational case series, patients admitted with toxin-induced
methemoglobinemia between September 2011 and January 2014 were identified from
the institutional poisoning database. Clinical profile and outcome of patients
with methemoglobin concentration greater than or equal to 49% is reported.
RESULTS: Of the 824 patients admitted with poisoning, 5 patients with
methemoglobin concentration greater than or equal to 49% were included. The
implicated compounds were nitrobenzene, benzoylphenylurea, flubendamide and
Rishab(TM). One patient refused to name the compound. All patients were managed
in the intensive care unit. Altered sensorium [Glasgow coma scale (GCS) < 10] was
common (80%); 2 patients presented with a GCS greater than 4. All patients
manifested cyanosis, low oxygen saturation and chocolate-brown-colored blood
despite supplemental oxygen therapy. The median methemoglobin concentration was
64.7% (range 49.8-91.6%); 2 patients had methemoglobin concentration greater than
70%. One patient needed inotropes. Four patients required mechanical ventilation
for 4-14 days. All patients were treated with methylene blue; 4 received more
than one dose. Three patients also received intravenous ascorbic acid 500 mg,
once daily, for 3 days. Following treatment, there was evidence of haemolysis in
all patients; 2 required blood transfusion. All patients survived. CONCLUSION:
Patients with severe toxin-induced methemoglobinemia present with altered
sensorium and cyanosis and may require ventilatory support and inotropes. Though
methemoglobin concentrations greater than 70% are considered fatal, aggressive
management with methylene blue and supportive therapy can lead to survival.
PMID- 25116419
TI - Features of myocardial injury in severe organophosphate poisoning.
AB - BACKGROUND: In organophosphate (OP) poisoning cardiac complications may occur.
However, the current body of knowledge largely consists of limited studies, and
case reports are mainly on electrocardiogram (ECG) abnormalities. As definite
myocardial injury is difficult to assess through ECG, we investigated the
prevalence of myocardial injury through cardiac biochemical markers such as
troponin I (TnI) in severe OP poisoning. METHODS: We conducted a retrospective
review of 99 consecutive OP insecticide poisoning cases that were diagnosed and
treated at the emergency department of the Wonju Severance Christian Hospital
between March 2008 and December 2013. RESULTS: Based on Namba classification for
OP poisoning, there were no patients with mild toxicity, 9 patients (9.1%) with
moderate toxicity and 90 patients (90.9%) with severe toxicity. On ECG, normal
sinus rhythm was most common, and ST depression and elevation were seen in 11
patients (11.1%). Elevation of TnI within 48 h was seen in 34 patients (34.3%).
The median peak level and peak time of TnI were 0.305 (IQR, 0.078-2.335) ng/mL
and 15 (IQR 6.9-34.4) hours, respectively. There were differences between
patients with normal TnI and elevated TnI in terms of age (yrs), number of
patients who were exposed to OP via the oral route, and initial Glasgow Coma
Scale (GCS; 58 +/- 17 vs. 66 +/- 16, p = 0.015, 56 [87.5%] vs. 33 [97.1%], p =
0.048 and 12.0 [IQR, 8.0-15.0] vs. 9.0 [IQR, 5.8-12.0], p = 0.019). CONCLUSIONS:
OP can cause direct myocardial injury during the acute early phase in severe OP
poisoning. Monitoring of TnI may be needed in severe OP poisoning.
PMID- 25116420
TI - Homeostatic regulation of meiotic DSB formation by ATM/ATR.
AB - Ataxia-telangiectasia mutated (ATM) and RAD3-related (ATR) are widely known as
being central players in the mitotic DNA damage response (DDR), mounting
responses to DNA double-strand breaks (DSBs) and single-stranded DNA (ssDNA)
respectively. The DDR signalling cascade couples cell cycle control to damage
sensing and repair processes in order to prevent untimely cell cycle progression
while damage still persists [1]. Both ATM/ATR are, however, also emerging as
essential factors in the process of meiosis; a specialised cell cycle programme
responsible for the formation of haploid gametes via two sequential nuclear
divisions. Central to achieving accurate meiotic chromosome segregation is the
introduction of numerous DSBs spread across the genome by the evolutionarily
conserved enzyme, Spo11. This review seeks to explore and address how cells
utilise ATM/ATR pathways to regulate Spo11-DSB formation, establish DSB
homeostasis and ensure meiosis is completed unperturbed.
PMID- 25116422
TI - A transnational perspective on psychosurgery: beyond Portugal and the United
States.
AB - The history of psychosurgery is most often recounted as a narrative wherein
Portuguese and American physicians play the leading role. It is a traditional
narrative in which the United States and, at times, Portugal are central in the
development and spread of psychosurgery. Here we largely abandon the archetypal
narrative and provide one of the first transnational accounts of psychosurgery to
demonstrate the existence of a global psychosurgical community in which more than
40 countries participated, bolstered, critiqued, modified and heralded the
treatment. From its inception in 1935 until its decline in the mid-1960s,
psychosurgery was performed on almost all continents. Rather than being a
phenomenon isolated to the United States and Portugal, it became a truly
transnational movement.
PMID- 25116421
TI - Helix stability of oligoglycine, oligoalanine, and oligo-beta-alanine dodecamers
reflected by hydrogen-bond persistence.
AB - Helices are important structural/recognition elements in proteins and peptides.
Stability and conformational differences between helices composed of alpha- and
beta-amino acids as scaffolds for mimicry of helix recognition has become a theme
in medicinal chemistry. Furthermore, helices formed by beta-amino acids are
experimentally more stable than those formed by alpha-amino acids. This is
paradoxical because the larger sizes of the hydrogen-bonding rings required by
the extra methylene groups should lead to entropic destabilization. In this
study, molecular dynamics simulations using the second-generation force field,
AMOEBA (Ponder, J.W., et al., Current status of the AMOEBA polarizable force
field. J Phys Chem B, 2010. 114(8): p. 2549-64.) explored the stability and
hydrogen-bonding patterns of capped oligo-beta-alanine, oligoalanine, and
oligoglycine dodecamers in water. The MD simulations showed that oligo-beta
alanine has strong acceptor+2 hydrogen bonds, but surprisingly did not contain a
large content of 3(12) -helical structures, possibly due to the sparse
distribution of the 3(12) -helical structure and other structures with acceptor+2
hydrogen bonds. On the other hand, despite its backbone flexibility, the beta
alanine dodecamer had more stable and persistent <3.0 A hydrogen bonds. Its
structure was dominated more by multicentered hydrogen bonds than either
oligoglycine or oligoalanine helices. The 3(1) (PII) helical structure, prevalent
in oligoglycine and oligoalanine, does not appear to be stable in oligo-beta
alanine indicating its competition with other structures (stacking structure as
indicated by MD analyses). These differences are among the factors that shape
helical structural preferences and the relative stabilities of these three
oligopeptides.
PMID- 25116423
TI - Exome sequencing of three cases of familial exceptional longevity.
AB - Exceptional longevity (EL) is a rare phenotype that can cluster in families, and
co-segregation of genetic variation in these families may point to candidate
genes that could contribute to extended lifespan. In this study, for the first
time, we have sequenced a total of seven exomes from exceptionally long-lived
siblings (probands >= 103 years and at least one sibling >= 97 years) that come
from three separate families. We have focused on rare functional variants (RFVs)
which have <= 1% minor allele frequency according to databases and that are
likely to alter gene product function. Based on this, we have identified one
candidate longevity gene carrying RFVs in all three families, APOB.
Interestingly, APOB is a component of lipoprotein particles together with APOE,
and variants in the genes encoding these two proteins have been previously
associated with human longevity. Analysis of nonfamilial EL cases showed a trend,
without reaching statistical significance, toward enrichment of APOB RFVs. We
have also identified candidate longevity genes shared between two families (5-13)
or within individual families (66-156 genes). Some of these genes have been
previously linked to longevity in model organisms, such as PPARGC1A, NRG1, RAD52,
RAD51, NCOR1, and ADCY5 genes. This work provides an initial catalog of genes
that could contribute to exceptional familial longevity.
PMID- 25116426
TI - Health behaviors of adults: United States, 2008-2010.
AB - Objective-This report presents selected prevalence estimates for key health
behaviors-alcohol use, cigarette smoking, leisure-time physical activity, body
mass index, and sleep-among U.S. adults, using data from the 2008-2010 National
Health Interview Survey (NHIS). NHIS is a continuous survey conducted annually by
the Centers for Disease Control and Prevention's National Center for Health
Statistics. Estimates are shown for several sociodemographic subgroups for both
sexes combined and for men and women separately. Methods-Data representing the
U.S. civilian noninstitutionalized population were collected using computer
assisted personal interviews. NHIS is a general purpose in-person household
survey, collecting basic health, health care utilization, and demographic
information on all household members with the Family questionnaire. Health
behavior questions are asked in the Sample Adult survey component. This report is
based on a total of 76,669 completed interviews with sample adults aged 18 and
over. Statistics shown in this report were age adjusted to the projected 2000
U.S. population. Results-About 6 in 10 (64.9%) U.S. adults were current drinkers
in 2008-2010; about 1 in 5 adults (20.9%) were lifetime abstainers. About one in
five adults (20.2%) were current smokers and over one-half of adults (58.6%) had
never smoked cigarettes. Less than one-half of current smokers (45.8%) attempted
to quit smoking in the past year. Nearly one-half (46.1%) of adults met the
federal guidelines for aerobic physical activity, about one-quarter (23.0%) of
adults met the federal guidelines for muscle-strengthening physical activity, and
about one in five adults (19.4%) met both guidelines. About 6 in 10 adults
(62.1%) were overweight or obese (BMI >= 25), with about 4 in 10 (36.1%) adults
being of healthy weight (18.5 <= BMI less than 25). About 7 in 10 adults (69.7%)
met the Healthy People 2020 objective for sufficient sleep.
PMID- 25116424
TI - Treatment with the antipsychotic agent, risperidone, reduces disease severity in
experimental autoimmune encephalomyelitis.
AB - Recent studies have demonstrated that atypical antipsychotic agents, which are
known to antagonize dopamine D2 and serotonin 5-HT2a receptors, have
immunomodulatory properties. Given the potential of these drugs to modulate the
immune system both peripherally and within the central nervous system, we
investigated the ability of the atypical anti-psychotic agent, risperidone, to
modify disease in the animal model of multiple sclerosis (MS)4, experimental
autoimune encephalomyelitis (EAE). We found that chronic oral administration of
risperidone dose-dependently reduced the severity of disease and decreased both
the size and number of spinal cord lesions. Furthermore, risperidone treatment
substantially reduced antigen-specific interleukin (IL)-17a, IL-2, and IL-4 but
not interferon (IFN)-gamma production by splenocytes at peak disease and using an
in vitro model, we show that treatment of macrophages with risperidone alters
their ability to bias naive T cells. Another atypical antipsychotic agent,
clozapine, showed a similar ability to modify macrophages in vitro and to reduce
disease in the EAE model but this effect was not due to antagonism of the type 1
or type 2 dopamine receptors alone. Finally, we found that while risperidone
treatment had little effect on the in vivo activation of splenic macrophages
during EAE, it significantly reduced the activation of microglia and macrophages
in the central nervous system. Together these studies indicate that atypical
antipsychotic agents like risperidone are effective immunomodulatory agents with
the potential to treat immune-mediated diseases such as MS.
PMID- 25116425
TI - Racial, social, and clinical determinants of hepatocellular carcinoma
surveillance.
AB - OBJECTIVES: Less than 1 in 5 patients receive hepatocellular carcinoma
surveillance; however, most studies were performed in racially and
socioeconomically homogenous populations, and few used guideline-based
definitions for surveillance. The study objective was to characterize guideline
consistent hepatocellular carcinoma surveillance rates and identify determinants
of hepatocellular carcinoma surveillance among a racially and socioeconomically
diverse cohort of cirrhotic patients. METHODS: We retrospectively characterized
hepatocellular carcinoma surveillance among cirrhotic patients followed between
July 2008 and July 2011 at an urban safety-net hospital. Inconsistent
surveillance was defined as at least 1 screening ultrasound during the 3-year
period, annual surveillance was defined as screening ultrasounds every 12 months,
and biannual surveillance was defined as screening ultrasounds every 6 months.
Univariate and multivariate analyses were conducted to identify predictors of
surveillance. RESULTS: Of 904 cirrhotic patients, 603 (67%) underwent
inconsistent surveillance. Failure to recognize cirrhosis was a significant
barrier to surveillance use (P < .001). Inconsistent surveillance was associated
with insurance status (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.03
1.98), multiple primary care visits per year (OR, 2.63; 95% CI, 1.86-3.71),
multiple hepatology visits per year (OR, 3.75; 95% CI, 2.64-5.33), African
American race (OR, 0.61; 95% CI, 0.42-0.99), nonalcoholic steatohepatitis cause
(OR, 0.60; 95% CI, 0.37-0.98), and extrahepatic cancer (OR, 0.43; 95% CI, 0.24
0.77). Only 98 (13.4%) of 730 patients underwent annual surveillance, and only 13
(1.7%) of 786 had biannual surveillance. CONCLUSIONS: Only 13% of patients with
cirrhosis receive annual surveillance, and less than 2% of patients receive
biannual surveillance. There are racial and socioeconomic disparities, with lower
rates of hepatocellular carcinoma surveillance among African Americans and
underinsured patients.
PMID- 25116427
TI - Safety and efficacy of warfarin plus aspirin combination therapy for giant
coronary artery aneurysm secondary to Kawasaki disease: a meta-analysis.
AB - OBJECTIVE: To compare the safety and efficacy of warfarin plus aspirin versus
aspirin alone for the treatment of children with giant coronary artery aneurysm
(CAA) secondary to Kawasaki disease (KD). METHODS: We searched the PubMed,
EMBASE, Cochrane Library, CNKI, WANFAN and VIP databases. We selected case
controlled trials of warfarin plus aspirin versus aspirin alone for the treatment
of children with giant CAA secondary to KD. RESULTS: Six retrospective studies
met our inclusion criteria. There was no significant difference between the
warfarin plus aspirin and aspirin alone groups in the rate of CAA regression (OR
1.38, 95% CI 0.52-3.68, p = 0.52) or the incidence of persistent CAA (OR 2.34,
95% CI 0.16-33.50, p = 0.53), coronary artery stenosis (OR 0.55, 95% CI 0.18
1.72, p = 0.30) or thrombus formation (OR 0.50, 95% CI 0.15-1.69, p = 0.26).
There was evidence that warfarin plus aspirin reduced the incidence of coronary
artery occlusion (OR 0.08, 95% CI 0.02-0.29, p < 0.0001), cardiac infarction (OR
0.27, 95% CI 0.11-0.63, p = 0.003) and death (OR 0.18, 95% CI 0.04-0.88, p =
0.03). CONCLUSION: Warfarin plus aspirin therapy reduced the incidence of
occlusion, cardiac infarction and death in children with giant CAA secondary to
KD.
PMID- 25116428
TI - Screening for bipolar disorder: confusion between case-finding and screening.
PMID- 25116429
TI - Red cell glucose 6-phosphate dehydrogenase deficiency in the northern region of
Turkey: is G6PD deficiency exclusively a male disease?
AB - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive
genetic defect that can cause hemolytic crisis. However, this disease affects
both males and females. In Turkey, the frequency of this enzyme deficiency was
reported to vary, from 0.25 to 18%, by the geographical area. Its prevalence in
the northern Black Sea region of Turkey is unknown. The aims of this study were
to assess the prevalence of G6PD deficiency in the northern region Turkey in
children and adults with hyperbilirubinemia and hemolytic anemia. This report
included a total of 976 G6PD enzyme results that were analyzed between May 2005
and January 2014. G6PD deficiency was detected in 5.0% of all patients. G6PD
deficiency was significantly less frequent in females (1.9%, 6/323) than in males
(6.6%, 43/653). G6PD deficiency was detected in 3.7% of infants with
hyperbilirubinemia, 9.2% of children, and 4.5% of adults with hemolytic anemia.
In both the newborn group and the group of children, G6PD deficiency was
significantly more frequent in males. In the combined group of children (groups I
and II), the proportion of males was 74% and 67% in all groups (P = .0008). In
conclusion, in northern region of Turkey, G6PD deficiency is an important cause
of neonatal hyperbilirubinemia and hemolytic crisis in children and adults. This
study suggests that most pediatricians thought that G6PD deficiency is
exclusively a male disease. For this reason, some female patients may have been
undiagnosed.
PMID- 25116431
TI - "Suddenly, bang, one day there's commitment with a woman..." men, vasectomy and
the life course.
AB - Research that investigates and theorises the male reproductive life course is
extremely limited, and often reduced to examining problems, such as infertility.
As a consequence, what we know about men's reproductive decision making is often
extrapolated from theorisation of the female reproductive life course, or
simplistic assumptions about masculine identity. This article analyses interview
data from 34 men talking about their vasectomy decision-making processes in order
to provide a lens through which to understand men making sense of their
reproductive life course. Men who had children spoke of their vasectomy as
resolving their lay understandings of the 'normal' life course, men who did not
want their children to speak of resisting the normal life course, and men who had
experienced or considered relationship dissolution spoke of resetting the life
course.
PMID- 25116433
TI - Facile formation of homoleptic Au(III) trications via simultaneous oxidation and
ligand delivery from [PhI(pyridine)2](2+).
AB - We report the first examples of Au(III) tricationic complexes bound only by
neutral monodentate ligands, which are a new class of gold reagents. Oxidative
addition to the bis-pyridine Au(I) cation, [Au(4-DMAP)2](+), using a series of
dicationic I(III) oxidants of the general form [PhI(L)2](2+) (L = pyridine, 4
DMAP, 4-cyanopyridine) allows ready access to homoleptic and pseudo-homoleptic
Au(III) complexes [Au(4-DMAP)2(L)2](3+). The facile oxidative addition of Au(I)
species additionally demonstrates the efficacy of PhI(L)2](2+) reagents as halide
free oxidants for Au(I). Comparisons are made via attempts to oxidize NHC
Au(I)Cl, where introduction of the chloride anion results in complex mixtures via
ligand and chloride exchange, demonstrating the advantage of using the pyridine
based homoleptic compounds. The new Au(III) trications show intriguing reactivity
with water, yielding dinuclear oxo-bridged and rare terminal Au(III)-OH
complexes.
PMID- 25116430
TI - Conserved expression of the GPR151 receptor in habenular axonal projections of
vertebrates.
AB - The habenula is a phylogenetically conserved brain structure in the epithalamus.
It is a major node in the information flow between fronto-limbic brain regions
and monoaminergic brainstem nuclei, and is thus anatomically and functionally
ideally positioned to regulate emotional, motivational, and cognitive behaviors.
Consequently, the habenula may be critically important in the pathophysiology of
psychiatric disorders such as addiction and depression. Here we investigated the
expression pattern of GPR151, a G protein-coupled receptor (GPCR), whose mRNA has
been identified as highly and specifically enriched in habenular neurons by in
situ hybridization and translating ribosome affinity purification (TRAP). In the
present immunohistochemical study we demonstrate a pronounced and highly specific
expression of the GPR151 protein in the medial and lateral habenula of rodent
brain. Specific expression was also seen in efferent habenular fibers projecting
to the interpeduncular nucleus, the rostromedial tegmental area, the rhabdoid
nucleus, the mesencephalic raphe nuclei, and the dorsal tegmental nucleus. Using
confocal microscopy and quantitative colocalization analysis, we found that
GPR151-expressing axons and terminals overlap with cholinergic, substance P
ergic, and glutamatergic markers. Virtually identical expression patterns were
observed in rat, mouse, and zebrafish brains. Our data demonstrate that GPR151 is
highly conserved, specific for a subdivision of the habenular neurocircuitry, and
constitutes a promising novel target for psychiatric drug development.
PMID- 25116434
TI - Gadolinium oxalate derivatives with enhanced magnetocaloric effect via
ionothermal synthesis.
AB - Two new oxalate-bridged Gd(III) coordination polymers, namely,
(choline)[Gd(C2O4)(H2O)3Cl]Cl.H2O (1) and [Gd(C2O4)(H2O)3Cl] (2), were first
obtained ionothermally by using a deep eutectic solvent (DES). The magnetic
studies and heat capacity measurements reveal that the two-dimensional Gd(III)
based coordination polymer of 2 has the higher magnetic density and exhibits a
larger cryogenic magnetocaloric effect (MCE) (DeltaS(m) = 48 J kg(-1) K(-1) for
DeltaH = 7 T at 2.2 K).
PMID- 25116437
TI - Foamy gland carcinoma in core needle biopsies of the prostate: clinicopathologic
and immunohistochemical study of 56 cases.
AB - Foamy gland carcinoma is a subtype of acinar adenocarcinoma characterized by
foamy appearance, large cytoplasm, pyknotic nuclei, inconspicuous nucleoli and
infiltrative pattern. In this study, we investigated the histological features
and the incidence of foamy gland carcinoma. We compared foamy gland carcinoma
with acinar adenocarcinoma according to age, prostate-specific antigen value,
Gleason score, peripheral nerve invasion and accompanying high-grade prostatic
intraepithelial neoplasia. Besides, we investigated the diagnostic value of
immunohistochemical markers in foamy gland carcinoma. A total of 863 TRUS-guided
prostate needle core biopsies performed at our hospital pathology clinic between
January 1, 2010, and December 31, 2011, were examined, 251 of these were
diagnosed acinar type adenocarcinoma. Conventional acinar type adenocarcinoma was
present in 195 (78%) cases, and foamy gland carcinoma, in 56 cases (22%). We
found that 11 (19%) of the 56 foamy gland carcinoma cases were pure and 45 (81%)
cases were mixed with conventional acinar type adenocarcinoma. Single-core
localization was present in 7 of 14 pure foamy gland carcinomas, and the number
of cases with a Gleason score of 7 and above was 21 (37%). No statistically
significant difference was found between foamy gland carcinoma and conventional
acinar type adenocarcinoma in terms of age, Gleason score, high-grade prostatic
intraepithelial neoplasia, and prostate-specific antigen values. Peripheral nerve
invasion was found to be statistically significantly more common in foamy gland
carcinoma compared to acinar type adenocarcinoma (P<.05). The staining percentage
of immunohistochemical markers in foamy gland carcinoma was 90.1% for p63, 90.6%
for 34Beta12 and 90.6% for AMACR.
PMID- 25116436
TI - Artesunate abolishes germinal center B cells and inhibits autoimmune arthritis.
AB - The antimalarial drug artemisinin and its derivatives exhibit potent
immunosuppressive activity in several autoimmune disease models, however the
mechanisms are not well-understood. This study was designed to investigate the
therapeutic effects and the underlying mechanisms of the artemisinin analog
artesunate using the K/BxN mouse model of rheumatoid arthritis. The well-studied
disease mechanisms of K/BxN model allowed us to pinpoint the effect of artesunate
on disease. Artesunate treatment prevented arthritis development in young K/BxN
mice by inhibiting germinal center (GC) formation and production of
autoantibodies. In adult K/BxN mice with established arthritis, artesunate
diminished GC B cells in a few days. However, artesunate did not affect the
follicular helper T cells (Tfh). In contrast to the spontaneous K/BxN model,
artesunate treatment exerted minor influence on K/BxN serum transfer induced
arthritis suggesting that artesunate has minimal effect on inflammatory responses
downstream of antibody production. Finally, we showed that artesunate
preferentially inhibits proliferating GC B cells. These results identify GC B
cells as a target of artesunate and provide a new rationale for using artemisinin
analogues to treat autoimmune diseases mediated by autoantibodies.
PMID- 25116439
TI - Autonomic healing of acrylic bone cement.
AB - Self-healing in orthopedic bone cement is demonstrated with a novel thermoplastic
solvent-bonding approach. Low toxicity solvent-filled microcapsules, embedded in
a commercial acrylic bone cement matrix, enable recovery of up to 80% of the
virgin fracture toughness of the cement at room and body temperature conditions
without external stimuli or human intervention.
PMID- 25116435
TI - Functional tooth restoration by next-generation bio-hybrid implant as a bio
hybrid artificial organ replacement therapy.
AB - Bio-hybrid artificial organs are an attractive concept to restore organ function
through precise biological cooperation with surrounding tissues in vivo. However,
in bio-hybrid artificial organs, an artificial organ with fibrous connective
tissues, including muscles, tendons and ligaments, has not been developed. Here,
we have enveloped with embryonic dental follicle tissue around a HA-coated dental
implant, and transplanted into the lower first molar region of a murine tooth
loss model. We successfully developed a novel fibrous connected tooth implant
using a HA-coated dental implant and dental follicle stem cells as a bio-hybrid
organ. This bio-hybrid implant restored physiological functions, including bone
remodelling, regeneration of severe bone-defect and responsiveness to noxious
stimuli, through regeneration with periodontal tissues, such as periodontal
ligament and cementum. Thus, this study represents the potential for a next
generation bio-hybrid implant for tooth loss as a future bio-hybrid artificial
organ replacement therapy.
PMID- 25116440
TI - Experimental and theoretical study of the influence of the state of dispersion of
graphene on the percolation threshold of conductive graphene/polystyrene
nanocomposites.
AB - The effect of the dispersed state of graphene is studied as a factor influencing
the electrical percolation threshold of graphene/polystyrene nanocomposites. We
find the percolation threshold of our nanocomposites, prepared with graphene
dispersions with different thermodynamic stabilities, degrees of exfoliation, and
size polydispersities, to range from 2 to 4.5 wt %. Connectedness percolation
theory is applied to calculate percolation thresholds of the corresponding
nanocomposites, based on the premise that size polydispersity of graphene
platelets in the corresponding solutions must have a strong influence on it.
Theory and experimental results agree qualitatively.
PMID- 25116442
TI - Investigation of acyl migration in mono- and dicaffeoylquinic acids under aqueous
basic, aqueous acidic, and dry roasting conditions.
AB - Acyl migration in chlorogenic acids describes the process of migration of
cinnamoyl moieties from one quinic acid alcohol group to another, thus
interconverting chlorogenic acid regioisomers. It therefore constitutes a special
case of transesterification reaction. Acyl migration constitutes an important
reaction pathway in both coffee roasting and brewing, altering the structure of
chlorogenic acid initially present in the green coffee bean. In this contribution
we describe detailed and comprehensive mechanistic studies comparing inter- and
intramolecular acyl migration involving the seven most common chlorogenic acids
in coffee. We employe aqueous acidic and basic conditions mimicking the brewing
of coffee along with dry roasting conditions. We show that under aqueous basic
conditions intramolecular acyl migration is fully reversible with basic
hydrolysis competing with acyl migration. 3-Caffeoylquinic acid was shown to be
most labile to basic hydrolysis. We additionally show that the acyl migration
process is strongly pH dependent with increased transesterification taking place
at basic pH. Under dry roasting conditions acyl migration competes with
dehydration to form lactones. We argue that acyl migration precedes
lactonization, with 3-caffeoylquinic acid lactone being the predominant product.
PMID- 25116432
TI - Phylogeny reconstruction and hybrid analysis of populus (Salicaceae) based on
nucleotide sequences of multiple single-copy nuclear genes and plastid fragments.
AB - Populus (Salicaceae) is one of the most economically and ecologically important
genera of forest trees. The complex reticulate evolution and lack of highly
variable orthologous single-copy DNA markers have posed difficulties in resolving
the phylogeny of this genus. Based on a large data set of nuclear and plastid DNA
sequences, we reconstructed robust phylogeny of Populus using parsimony, maximum
likelihood and Bayesian inference methods. The resulting phylogenetic trees
showed better resolution at both inter- and intra-sectional level than previous
studies. The results revealed that (1) the plastid-based phylogenetic tree
resulted in two main clades, suggesting an early divergence of the maternal
progenitors of Populus; (2) three advanced sections (Populus, Aigeiros and
Tacamahaca) are of hybrid origin; (3) species of the section Tacamahaca could be
divided into two major groups based on plastid and nuclear DNA data, suggesting a
polyphyletic nature of the section; and (4) many species proved to be of hybrid
origin based on the incongruence between plastid and nuclear DNA trees.
Reticulate evolution may have played a significant role in the evolution history
of Populus by facilitating rapid adaptive radiations into different environments.
PMID- 25116443
TI - Robust image registration of biological microscopic images.
AB - Image registration of biological data is challenging as complex deformation
problems are common. Possible deformation effects can be caused in individual
data preparation processes, involving morphological deformations, stain
variations, stain artifacts, rotation, translation, and missing tissues. The
combining deformation effects tend to make existing automatic registration
methods perform poor. In our experiments on serial histopathological images, the
six state of the art image registration techniques, including TrakEM2, SURF +
affine transformation, UnwarpJ, bUnwarpJ, CLAHE + bUnwarpJ and BrainAligner,
achieve no greater than 70% averaged accuracies, while the proposed method
achieves 91.49% averaged accuracy. The proposed method has also been demonstrated
to be significantly better in alignment of laser scanning microscope brain images
and serial ssTEM images than the benchmark automatic approaches (p < 0.001). The
contribution of this study is to introduce a fully automatic, robust and fast
image registration method for 2D image registration.
PMID- 25116441
TI - The ruthenium nitric oxide donor, [Ru(HEDTA)NO], inhibits acute nociception in
mice by modulating oxidative stress, cytokine production and activating the
cGMP/PKG/ATP-sensitive potassium channel signaling pathway.
AB - Nitric oxide plays an important role in various biological processes including
antinociception. The control of its local concentration is crucial for obtaining
the desired effect and can be achieved with exogenous nitric oxide-carriers such
as ruthenium complexes. Therefore, we evaluated the analgesic effect and
mechanism of action of the ruthenium nitric oxide donor [Ru(HEDTA)NO] focusing on
the role of cytokines, oxidative stress and activation of the cyclic guanosine
monophosphate/protein kinase G/ATP-sensitive potassium channel signaling pathway.
It was observed that [Ru(HEDTA)NO] inhibited in a dose-dependent (1-10 mg/kg)
manner the acetic acid-induced writhing response. At the dose of 1 mg/kg,
[Ru(HEDTA)NO] inhibited the phenyl-p-benzoquinone-induced writhing response, and
formalin- and complete Freund's adjuvant-induced licking and flinching responses.
Systemic and local treatments with [Ru(HEDTA)NO] also inhibited the carrageenin
induced mechanical hyperalgesia and increase of myeloperoxidase activity in paw
skin samples. Mechanistically, [Ru(HEDTA)NO] inhibited carrageenin-induced
production of the hyperalgesic cytokines tumor necrosis factor-alpha and
interleukin-1beta, and decrease of reduced glutathione levels. Furthermore, the
inhibitory effect of [Ru(HEDTA)NO] in the carrageenin-induced hyperalgesia and
myeloperoxidase activity was prevented by the treatment with ODQ (soluble
guanylyl cyclase inhibitor), KT5823 (protein kinase G inhibitor) and
glybenclamide (ATP-sensitive potassium channel inhibitor), indicating that
[Ru(HEDTA)NO] inhibits inflammatory hyperalgesia by activating the cyclic
guanosine monophosphate/protein kinase G/ATP-sensitive potassium channel
signaling pathway, respectively. These results demonstrate that [Ru(HEDTA)NO]
exerts its analgesic effect in inflammation by inhibiting pro-nociceptive
cytokine production, oxidative imbalance and activation of the nitric
oxide/cyclic guanosine monophosphate/protein kinase G/ATP-sensitive potassium
channel signaling pathway in mice.
PMID- 25116444
TI - Serum Dickkopf-1 expression level positively correlates with a poor prognosis in
breast cancer.
AB - BACKGROUND: The different expression level of Dickkopf-1 (DKK-1) in different
cancers shows that the function of DKK-1 depends on the histological type of the
cancer cells and the tissue microenvironment. To our knowledge, the serum
expression level of DKK-1 in breast cancer is little known. METHODS: Blood
samples from 125 consecutive patients diagnosed with breast cancer and 53 control
subjects from March 2008 to August 2013 were investigated. Serum DKK-1 expression
levels were measured by enzyme-linked immunosorbent assay (ELISA). The overall
survival (OS) and relapse-free survival (RFS) analyzed by log-rank test, and
survival curves were plotted according to Kaplan-Meier. RESULTS: The mean serum
level of DKK-1 in patients with breast cancer was 4.99 +/- 1.50 ng/mL, and was
significantly higher than that in healthy individuals (1.88 +/- 0.81 ng/mL, P <
0.001). DKK-1 level correlated significantly with TNM stage (P = 0.009), tumor
grade (P = 0.02), lymph node metastasis (P = 0.001), and expression of HER2 (P =
0.002). The DKK-1 expression level was classified as high or low in relation to
the median value, and patients with breast cancer (n = 125) were divided into a
high expression group (n = 63) and a low expression group (n = 62). The Kaplan
Meier method for survival analysis showed that the patients with a high serum DKK
1 level had a poorer OS (48.7% vs. 81.3%, p = 0.01) and RFS (24.3% vs. 71.6%, p =
0.003) than those with a low expression level. The multivariate Cox regression
analysis indicated that serum DKK-1 level was independent prognostic factors for
OS and RFS. CONCLUSIONS: Serum DKK-1 level can be used as a noninvasive biomarker
for the prognosis of breast cancer. VIRTUAL SLIDES: The virtual slide(s) for this
article can be found here:
http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_161.
PMID- 25116446
TI - Clinical utility of an observation and response chart with human factors design
characteristics and a track and trigger system: study protocol for a two-phase
multisite multiple-methods design.
AB - BACKGROUND: Clinical deterioration of adult patients in acute medical-surgical
wards continues to occur, despite a range of systems and processes designed to
minimize this risk. In Australia, a standardized template for adult observation
charts using human factors design principles and decision-support characteristics
was developed to improve the detection of and response to abnormal vital signs.
OBJECTIVE: To describe the study protocol for the clinical testing of these
observation and response charts (ORCs). METHODS: We propose a two-phase multisite
multiple-methods design to test the initial clinical utility of the charts in 10
hospitals of differing types and sizes across state jurisdictions in Australia.
Data collection in the first phase includes user surveys, observations and field
notes by project officers, handover de-briefs (short interviews with small groups
of staff), and an audit of ORC documentation completion compared to the site's
existing observation chart. For the second phase, data will be collected using a
retrospective audit of observation documentation from the previous hospital
observation chart, prospective audit of observation documentation following
implementation of the selected ORC, user focus groups, observational field notes,
and patient outcome data from routinely collected organizational data sources.
RESULTS: Site selection and preparation, project officer training, chart
selection and implementation, participant recruitment, and data collection has
been completed and the analysis of these results are in progress. CONCLUSIONS:
This detailed description of these study methods and data collection approaches
will enable a comprehensive assessment of the clinical utility of these newly
developed track and trigger charts and will be useful for clinicians and
researchers when planning and implementing similar studies. Potential
methodological limitations are also noted.
PMID- 25116447
TI - Oxidative stress and biochemical responses in the tissues of African catfish
Clarias gariepinus juvenile following exposure to primextra herbicide.
AB - Primextra is a commercial herbicide formulation generally used in agriculture for
weed control. The present study was designed to investigate the oxidative stress
biomarkers and biochemical responses in the tissues of Clarias gariepinus
juvenile exposed to primextra. Fish were exposed to 0.24 and 0.47 mgL(-1)
corresponding to 1/20 and 1/10th of 96 h LC50 of the herbicide. The liver and
muscle tissues were sampled on day 1, 5, 10 and 15 and results showed
concentration and time dependent significant increase (p < 0.05) in the values of
lipid peroxidation, glutathione peroxidase, catalase and alkaline phosphatase in
both tissues. A marked significant increase (p < 0.05) was observed in the values
of aspartate aminotransferase, alanine aminotransferase and glucose in the liver
while a mixed trend in their values were observed in the muscle. The values of
superoxide dismutase and protein in both tissues were comparable to the control
except on day 15 in the liver where the values significantly declined. The
condition factor was not directly affected but values of hepatosomatic index were
significantly reduced. The present findings revealed that primextra induced toxic
stress even at sublethal concentrations resulting in alterations of the studied
parameters which were more evident in the fish liver than in the muscle tissue.
PMID- 25116448
TI - Effect of internal structure of collagen/hydroxyapatite scaffold on the
osteogenic differentiation of mesenchymal stem cells.
AB - Consisting of seed cells and scaffold, regenerative medicine provides a new way
for the repair and regeneration of tissue and organ. Collagen/hydroxyapatite (HA)
biocomposite scaffold is highlighted due to its advantageous features of two
major components of bone matrix: collagen and HA. The aim of this study is to
investigate the effect of internal structure of collagen/HA scaffold on the fate
of rat mesenchymal stem cells (MSCs). The internal structure of collagen/HA
scaffold was characterized by micro-CT. It is found that the porosity decreased
while average compressive modulus increased with the increase of collagen
proportion. Within the collagen proportion of 0.35%, 0.5% and 0.7%, the
porosities were 89.08%, 78.37% and 75.36%, the pore sizes were 140.6+/-75.5 MUm,
133.9+/-48.4 MUm and 160.7+/-119.6 MUm, and the average compressive moduli were
6.74+/-1.16 kPa, 8.82+/-2.12 kPa and 23.61+/-8.06 kPa, respectively. Among these
three kinds of scaffolds, MSCs on the Col 0.35/HA 22 scaffold have the highest
viability and the best cell proliferation. On the contrary, the Col 0.7/HA 22
scaffold has the best ability to stimulate MSCs to differentiate into osteoblasts
in a relatively short period of time. In vivo research also demonstrated that the
internal structure of collagen/HA scaffold has significant effect on the cell
infiltration. Therefore, precise control of the internal structure of collagen/HA
scaffold can provide a more efficient carrier to the repair of bone defects.
PMID- 25116449
TI - Role of signaling pathways in mesenchymal stem cell differentiation.
AB - Mesenchymal Stem Cells (MSCs) are self-renewing cells with ability to
differentiate into organized, functional network of cells. In recent past
research in developing clinical applications for MSCs has increased
significantly. MSCs exhibit multi potential proliferation, and are capable of
differentiating into cartilage, bone, neuronal cells and adipocytes, etc.
Signaling pathways, transcription factors and growth factors modulate the
differentiation of MSCs into different cell lineages. Besides, physical factors
may regulate the molecular differentiation of stem cells. The main theme of this
paper is to review the signaling pathways related to bone morphogenetic proteins
(BMPs), epidermal growth factors (EGF), transforming growth factors (TGF),
wingless type MMTV integration site (wnt) proteins, fibroblastic growth factor
(FGF), and transcriptional regulating factors significance in the MSCs
differentiation.
PMID- 25116450
TI - Role of inflammation and tumor microenvironment in the development of
gastrointestinal cancers: what induced pluripotent stem cells can do?
AB - Connections between inflammation and cancer are a rapidly developing field. Some
gastrointestinal tract cancers arise from infection, chronic irritation, and
ensuing inflammation. Cellular effectors and mediators are important constituents
of the tumor microenvironment, including neoplastic, stromal, and migratory
hematopoietic cells. Complex interaction between these cells in the tumor
microenvironment regulates tumor growth, progression, metastasis, and
angiogenesis. Tumor-associated macrophages represent the major inflammatory cell
population in tumors, which orchestrate various aspects of cancer. Cytokines and
chemokines are major mediators of communication between cells in the tumor
microenvironment. The concept of oncogene builds up an inflammatory pre
neoplastic microenvironment has emerged in the last few years. On the other hand,
the development of induced pluripotent stem cells (iPSCs) unraveled a mystery in
stem cell research. However, there are still some debates about iPSCs which
should be answered by science.
PMID- 25116451
TI - Toxicological analysis and antihyperalgesic, antidepressant, and anti
inflammatory effects of Campomanesia adamantium fruit barks.
AB - OBJECTIVE: This study evaluates the anti-inflammatory, antihyperalgesic, and
antidepressive potential of the hydroalcoholic extract of Campomanesia adamantium
fruit barks (CAE) on rodents and determines the safety of this plant. METHODS:
The acute toxicity of CAE was evaluated by oral administration to female rats as
single doses of 0, 500, 1000, or 2000 mg/kg body weight. General behavior and
toxic symptoms were observed for 14 days. In the subacute toxicity test, male and
female rats received 125 or 250 mg/kg body weight of CAE for 28 days. The oral
anti-inflammatory activity of CAE was evaluated in carrageenan-induced pleurisy
in male mice. The effect of treatment with CAE (100 mg/kg) for 15 days was
evaluated in mechanical hyperalgesia (electronic von Frey), depressive behavior
(forced swimming test), and cold hypersensitivity in spared nerve injury (SNI)
model in rats. RESULTS: No clinical signs of toxicity were observed in animals
from the experimental groups during acute and subacute exposure to CAE. At
pleurisy test, the oral administration of CAE significantly inhibited leukocyte
migration and protein leakage at all doses tested when compared to control. Oral
administration of CAE for 3-15 days significantly inhibited SNI-induced
mechanical hyperalgesia and increased immobility in the forced swim test.
Finally, on the 15th day, oral treatment with CAE prevented the increase in
sensitivity to a cold stimulus induced by SNI. DISCUSSION: The present study
shows that C. adamantium extract has anti-inflammatory, antihyperalgesic, and
antidepressive properties in rodents without causing toxicity.
PMID- 25116452
TI - Functional regulation of neuronal nitric oxide synthase expression and activity
in the rat retina.
AB - In the nervous system within physiological conditions, nitric oxide (NO)
production depends on the activity of nitric oxide synthases (NOSs), and
particularly on the expression of the neuronal isoform (nNOS). In the sensory
systems, the role of NO is poorly understood. In this study, we identified nNOS
positive cells in the inner nuclear layer (INL) of the rat retina, with distinct
characteristics such as somata size, immunolabeling level and location. Employing
mathematical cluster analysis, we determined that nNOS amacrine cells are formed
by two distinct populations. We next investigated the molecular identity of these
cells, which did not show colocalization with calbindin (CB), choline
acetyltransferase (ChAT), parvalbumin (PV) or protein kinase C (PKC), and only
partial colocalization with calretinin (CR), revealing the accumulation of nNOS
in specific amacrine cell populations. To access the functional, circuitry
related roles of these cells, we performed experiments after adaptation to
different ambient light conditions. After 24h of dark-adaptation, we detected a
subtle, yet statistically significant decrease in nNOS transcript levels, which
returned to steady-state levels after 24h of normal light-dark cycle, revealing
that nNOS expression is governed by ambient light conditions. Employing electron
paramagnetic resonance (EPR), we demonstrated that dark-adaptation decreases NO
production in the retina. Furthermore, nNOS accumulation changed in the dark
adapted retinas, with a general reduction in the inner plexiform layer. Finally,
computational analysis based on clustering techniques revealed that dark
adaptation differently affected both types of nNOS-positive amacrine cells. Taken
together, our data disclosed functional regulation of nNOS expression and
activity, disclosing new circuitry-related roles of nNOS-positive cells. More
importantly, this study indicated unsuspected roles for NO in the sensory
systems, particularly related to adaptation to ambient demands.
PMID- 25116453
TI - Binding mode analysis of a major T3SS translocator protein PopB with its
chaperone PcrH from Pseudomonas aeruginosa.
AB - Pseudomonas aeruginosa, a Gram-negative pathogen uses a specialized set of Type
III secretion system (T3SS) translocator proteins to establish virulence in the
host cell. An understanding of the factors that govern translocation by the
translocator protein-chaperone complex is thus of immense importance. In this
work, experimental and computational techniques were used to probe into the
structure of the major translocator protein PopB from P. aeruginosa and to
identify the important regions involved in functioning of the translocator
protein. This study reveals that the binding sites of the common chaperone PcrH,
needed for maintenance of the translocator PopB within the bacterial cytoplasm,
which are primarily localized within the N-terminal domain. However, disordered
and flexible residues located both at the N- and C-terminal domains are also
observed to be involved in association with the chaperone. This intrinsic
disorderliness of the terminal domains is conserved for all the major T3SS
translocator proteins and is functionally important to maintain the intrinsically
disordered state of the translocators. Our experimental and computational
analyses suggest that a "disorder-to-order" transition of PopB protein might take
place upon PcrH binding. The long helical coiled-coil part of PopB protein
perhaps helps in pore formation while the flexible apical region is involved in
chaperone interaction. Thus, our computational model of translocator protein PopB
and its binding analyses provide crucial functional insights into the T3SS
translocation mechanism.
PMID- 25116445
TI - Targeted nanotechnology for cancer imaging.
AB - Targeted nanoparticle imaging agents provide many benefits and new opportunities
to facilitate accurate diagnosis of cancer and significantly impact patient
outcome. Due to the highly engineerable nature of nanotechnology, targeted
nanoparticles exhibit significant advantages including increased contrast
sensitivity, binding avidity and targeting specificity. Considering the various
nanoparticle designs and their adjustable ability to target a specific site and
generate detectable signals, nanoparticles can be optimally designed in terms of
biophysical interactions (i.e., intravascular and interstitial transport) and
biochemical interactions (i.e., targeting avidity towards cancer-related
biomarkers) for site-specific detection of very distinct microenvironments. This
review seeks to illustrate that the design of a nanoparticle dictates its in vivo
journey and targeting of hard-to-reach cancer sites, facilitating early and
accurate diagnosis and interrogation of the most aggressive forms of cancer. We
will report various targeted nanoparticles for cancer imaging using X-ray
computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and
optical imaging. Finally, to realize the full potential of targeted
nanotechnology for cancer imaging, we will describe the challenges and
opportunities for the clinical translation and widespread adaptation of targeted
nanoparticles imaging agents.
PMID- 25116454
TI - Tackle-related injury rates and nature of injuries in South African Youth Week
tournament rugby union players (under-13 to under-18): an observational cohort
study.
AB - OBJECTIVES: The tackle situation is most often associated with the high injury
rates in rugby union. Tackle injury epidemiology in rugby union has previously
been focused on senior cohorts but less is known about younger cohorts. The aim
of this study was to report on the nature and rates of tackle-related injuries in
South African youth rugby union players representing their provinces at national
tournaments. DESIGN: Observational cohort study. SETTING: Four South African
Youth Week tournaments (under-13 Craven Week, under-16 Grant Khomo Week, under-18
Academy Week, under-18 Craven Week). PARTICIPANTS: Injury data were collected
from 3652 youth rugby union players (population at risk) in 2011 and 2012.
OUTCOME MEASURES: Tackle-related injury severity ('time-loss' and 'medical
attention'), type and location, injury rate per 1000 h (including 95% CIs).
Injury rate ratios (IRR) were calculated and modelled using a Poisson regression.
A chi(2) analysis was used to detect linear trends between injuries and
increasing match quarters. RESULTS: The 2012 under-13 Craven Week had a
significantly greater 'time-loss' injury rate when compared with the 2012 under
18 Academy Week (IRR=4.43; 95% CI 2.13 to 9.21, p<0.05) and under-18 Craven Week
(IRR=3.52; 95% CI 1.54 to 8.00, p<0.05). The Poisson regression also revealed a
higher probability of 'overall' ('time-loss' and 'medical attention' combined)
and 'time-loss' tackle-related injuries occurring at the under-13 Craven Week.
The proportion of 'overall' and 'time-loss' injuries increased significantly with
each quarter of the match when all four tournaments were combined (p<0.05).
CONCLUSIONS: There was a difference in the tackle-related injury rate between the
under-13 tournament and the two under-18 tournaments, and the tackle-related
injury rate was higher in the final quarter of matches. Ongoing injury
surveillance is required to better interpret these findings. Injury prevention
strategies targeting the tackle may only be effective once the rate and nature of
injuries have been accurately determined.
PMID- 25116456
TI - The positive pharmacy care law: an area-level analysis of the relationship
between community pharmacy distribution, urbanity and social deprivation in
England.
AB - OBJECTIVES: To: (1) determine the percentage of the population in England that
have access to a community pharmacy within 20 min walk; (2) explore any
relationship between the walking distance and urbanity; (3) explore any
relationship between the walking distance and social deprivation; and (4) explore
any interactions between urbanity, social deprivation and community pharmacy
access. DESIGN: This area level analysis spatial study used postcodes for all
community pharmacies in England. Each postcode was assigned to a population
lookup table and lower super output area (LSOA). The LSOA was then matched to
urbanity (urban, town and fringe or village, hamlet and isolated dwellings) and
deprivation decile (using the Index of Multiple Deprivation score). PRIMARY
OUTCOME MEASURE: Access to a community pharmacy within 20 min walk. RESULTS:
Overall, 89.2% of the population is estimated to have access to a community
pharmacy within 20 min walk. For urban areas, that is 98.3% of the population,
for town and fringe, 79.9% of the population, while for rural areas, 18.9% of the
population. For areas of lowest deprivation (deprivation decile 1) 90.2% of the
population have access to a community pharmacy within 20 min walk, compared to
99.8% in areas of highest deprivation (deprivation decile 10), a percentage
difference of 9.6% (8.2, 10.9). CONCLUSIONS: Our study shows that the majority of
the population can access a community pharmacy within 20 min walk and crucially,
access is greater in areas of highest deprivation--a positive pharmacy care law.
More research is needed to explore the perceptions and experiences of people-
from various levels of deprivation--around the accessibility of community
pharmacy services.
PMID- 25116455
TI - Can training in advanced clinical skills in obstetrics, neonatal care and
leadership, of non-physician clinicians in Malawi impact on clinical services
improvements (the ETATMBA project): a process evaluation.
AB - OBJECTIVES: The 'enhancing human resources and the use of appropriate
technologies for maternal and perinatal survival in sub-Saharan Africa' (ETATMBA)
project is training emergency obstetric and new-born care (EmONC) non-physician
clinicians (NPCs) as advanced clinical leaders. Our objectives were to evaluate
the implementation and changes to practice. DESIGN: A mixed methods process
evaluation with the predominate methodology being qualitative. SETTING: Rural and
urban hospitals in 8 of the 14 districts of northern and central Malawi.
PARTICIPANTS: 54 EmONC NPCs with 3 years' plus experience. INTERVENTION: Training
designed and delivered by clinicians from the UK and Malawi; it is a 2-year plus
package of training (classroom, mentorship and assignments). RESULTS: We
conducted 79 trainee interviews over three time points during the training, as
well as a convenience sample of 10 colleagues, 7 district officers and 2 UK
obstetricians. Trainees worked in a context of substantial variation in the rates
of maternal and neonatal deaths between districts. Training reached trainees
working across the target regions. For 46 trainees (8 dropped out of the course),
dose delivered in terms of attendance was high and all 46 spent time working
alongside an obstetrician. In early interviews trainees recalled course content
unprompted indicating training had been received. Colleagues and district
officers reported cascading of knowledge and initial changes in practice
indicating early implementation. By asking trainees to describe actual cases we
found they had implemented new knowledge and skills. These included life-saving
interventions for postpartum haemorrhage and eclampsia. Trainees identified the
leadership training as enabling them to confidently change their own practice and
initiate change in their health facility. CONCLUSIONS: This process evaluation
suggests that trainees have made positive changes in their practice. Clear
impacts on maternal and perinatal mortality are yet to be elucidated.
PMID- 25116457
TI - Arterial stiffness and wave reflection 1 year after a pregnancy complicated by
hypertension.
AB - Hypertensive disorders of pregnancy (HDP) are associated with cardiovascular
disease (CVD) later in life. The authors investigated the association of HDP with
blood pressure (BP) and arterial stiffness 1-year postpartum. Seventy-four
participants, 33 with an HDP and 41 with uncomplicated pregnancies, were examined
using applanation tonometry to measure BP, carotid-femoral pulse wave velocity
(cfPWV), and augmentation index (AIx). On average, women with HDP had a 9 mm
higher systolic BP (P<.01), 0.8 m/s faster cfPWV (P=.09), and 5.4% greater AIx
(P=.09) at the 1-year examination. After adjustment for covariates, there was no
significant difference in cfPWV between groups, while a 7.3% greater AIx (P<.05)
remained. These findings suggest that reduced endothelial function may be
detected 1 year after HDP. Large prospective studies are needed to further
understand the contribution of arterial stiffness and endothelial dysfunction in
the evolution of CVD after these complicated pregnancies.
PMID- 25116459
TI - Papillary thyroid microcarcinoma in a thyroid pyramidal lobe.
AB - We report an extremely rare case of papillary thyroid microcarcinoma (PTMC) in
the thyroid Epub ahead of print pyramidal lobe (TPL). A 48-year-old woman
underwent ultrasound-guided fine-needle aspiration for a small thyroid nodule in
the right lobe in local clinic, and it revealed a malignant cytology. On
preoperative ultrasonography for tumor staging in our hospital, another small
suspiciously malignant hypoechoic nodule was detected in the left TPL. Total
thyroidectomy and central nodal dissection were performed. Histopathology
confirmed PTMCs in the left TPL and both thyroid lobes. Ultrasonography for TPL
should be required for complete evaluation of possible multifocality of thyroid
malignancy.
PMID- 25116460
TI - Theoretical study on reaction mechanism of ground-state cyano radical with 1,3
butadiene: prospect of pyridine formation.
AB - The reaction of ground-state cyano radicals, CN(X(2)Sigma(+)), with the simplest
polyene, 1,3-butadiene (C4H6(X(1)Ag)), is investigated to explore probable routes
and feasibility to form pyridine at ultralow temperatures. The isomerization and
dissociation channels for each of the seven initial collision complexes are
characterized by utilizing the unrestricted B3LYP/cc-pVTZ and the CCSD(T)/cc-pVTZ
calculations. With facilitation of RRKM rate constants, through ab initio paths
composed of 7 collision complexes, 331 intermediates, 62 hydrogen atom, 71
hydrogen molecule, and 3 hydrogen cyanide dissociated products, the most probable
paths at collision energies up to 10 kcal/mol, and thus the reaction mechanism,
are determined. Subsequently, the corresponding rate equations are solved that
the concentration evolutions of collision complexes, intermediates, and products
versus time are obtained. As a result, the final products and yields are
determined. The low-energy routes for the formation of most thermodynamically
stable product, pyridine, are identified. This study, however, predicts that
seven collision complexes would produce predominately 1-cyano-1,3-butadiene,
CH2CHCHCHCN (p2) plus atomic hydrogen via the collision complex c1(CH2CHCHCH2CN)
and intermediate i2(CH2CHCH2CHCN), with a very minor amount of pyridine. Our
scheme also effectively excludes the presence of 2-cyano-1,3-butadiene, which has
energy near-degenerate to 1-cyano-1,3-butadiene, as supported by experimental
findings.
PMID- 25116458
TI - Fetal tumors: prenatal ultrasonographic findings and clinical characteristics.
AB - The incidence of fetal tumors has been increased due to generalization of
prenatal evaluation and improvement of imaging techniques. The early detection of
a fetal tumor and understanding of its imaging features are very important for
fetal, maternal, and neonatal care. Ultrasonography is usually used for the
detection and differential diagnosis of fetal tumors, and magnetic resonance
imaging is increasingly being used as a complementary study. Many fetal tumors
have different clinical and imaging features compared with pediatric tumors.
Although several fetal tumors may mimic other common anomalies, some specific
imaging features may carry early accurate diagnosis of fetal tumors, which may
alter the prenatal management of a pregnancy and the mode of delivery, and
facilitate immediate postnatal treatment.
PMID- 25116461
TI - The effectiveness of the cognitive behavioral analysis system of psychotherapy
for chronic depression: a randomized controlled trial.
AB - BACKGROUND: It is widely agreed that chronic depression is difficult to treat,
knowledge about optimal treatment approaches is emerging. METHOD: A multisite
randomized controlled trial was conducted comparing the cognitive behavioral
analysis system of psychotherapy (CBASP), a psychotherapy model developed
specifically to treat chronic depression (n = 67) with care as usual (CAU;
evidence-based treatments, n = 72) over a period of 52 weeks, with 23 sessions on
average, in 3 outpatient clinics in the Netherlands. In both arms algorithm-based
pharmacotherapy was provided. Patients (aged 18-65) met criteria for a DSM-IV
diagnosis of major depressive disorder with diagnostic specifiers (chronic,
without interepisode recovery) or with co-occurring dysthymic disorder indicating
a chronic course. The Inventory for Depressive Symptomatology (IDS) Self-Report
was used as the primary outcome measure. Mixed-effects linear regression analysis
was used to compare the changes on the IDS scores between CBASP and CAU. The IDS
was administered before treatment, and after 8, 16, 32 and 52 weeks. RESULTS: At
week 52, patients assigned to CBASP had a greater reduction of depressive
symptoms compared to patients assigned to CAU (t = -2.00, p = 0.05). However,
CBASP and CAU did not differ from each other on the IDS after 8 weeks (t = 0.49,
p = 0.63), 16 weeks (t = -0.03, p = 0.98) and 32 weeks (t = -0.17, p = 0.86) of
treatment. CONCLUSIONS: This trial shows that CBASP is at least as effective as
standard evidence-based treatments for chronic depression. In the long run, CBASP
appears to have an added effect.
PMID- 25116463
TI - Isolated right-sided mural infective endocarditis in a 32-year-old woman with
muscular ventricular septal defect.
AB - Bacterial endocarditis secondary to jet streams from a congenital heart defect
without valvular involvement is very rare, especially in adult patients. We
report an unusual case of a 32-year-old woman with a previously known unrepaired
ventricular septal defect (VSD) who presented with intermittent fever and chills
after dental treatment and was diagnosed with isolated right-sided mural
infective endocarditis associated with a muscular-type VSD. Echocardiography
revealed a low echogenic, mobile vegetation along the right ventricular outflow
tract (RVOT) free wall and a small-sized muscular-type VSD. The patient's blood
culture grew Streptococcus viridians. After 3 weeks of antibiotic treatment, VSD
patch closure was performed, and the vegetation on the RVOT endomyocardium was
removed.
PMID- 25116464
TI - Clinical features and treatment results of children with diffuse large B-cell
lymphoma.
AB - The demographic, clinical characteristics, and treatment groups of 33 children
with diffuse large B-cell lymphoma (DLBCL) were recorded and analyzed among 1486
non-Hodgkin lymphoma (NHL) cases since 1972. The median age was 9.7 years (range
1.4-16.9) and male/female ratio was 24/9 = 2.6. Kaplan-Meier methods and logrank
tests were used in treatment analysis. The frequency of DLBCL among 1486 NHL
cases was 2.2%, however, the percentage was 9.3% in cases diagnosed after 2000.
The event-free survival (EFS) and overall survival (OS) rates for 33 children
were 61% and 65.1% at 5 years, respectively. The EFS and OS rates of low stage
(stages I and II) disease decreased to lower level in advanced stage (stages III
and IV) disease. Associated conditions and ages older than 14 years were found as
poor prognostic factors in multivariate analysis. The survival rates in children
with DLBCL need further improvement. This is mainly related with late referral of
those children with advanced disease. The proper diagnosis and early referral is
essential in these children for a better survival rate. The children with
associated conditions and older children must be handled with care since these
are found as poor prognostic factors.
PMID- 25116466
TI - Midwives' personal experiences of pregnancy and childbirth: Exploring issues of
autonomy and agency in relation to the use of professional knowledge.
AB - This paper seeks to explore midwives' experiences of pregnancy and childbirth. It
draws on interviews with nine midwives who completed their midwifery training
prior to becoming mothers, to discuss how midwives use their professional
knowledge to exercise agency (the choices made about their own care), and assume
autonomy (the control and responsibility in relation to their own care), in
pregnancy and childbirth. It illustrates that a reliance on professional
knowledge may create opportunities for choice and increased autonomy in some
situations, although the need for intervention during childbirth, for example,
may challenge the degree of autonomy exercised by midwives and the choices
available to them. As knowledgeable experts, midwives demonstrate a very
different understanding of risk and safety in relation to their own experiences
of childbirth. Professional knowledge may increase their anxieties which may not
be addressed appropriately by caregivers due to their professional status. The
use of knowledge in this way highlights potential conflict between their position
as midwives and their experience as mothers, illustrating that midwives' ability
to exercise agency and autonomy in relation to their pregnancy and childbirth
experiences is potentially problematic.
PMID- 25116465
TI - Biomarkers of dissolved oxygen stress in oysters: a tool for restoration and
management efforts.
AB - The frequency and intensity of anoxic and hypoxic events are increasing
worldwide, creating stress on the organisms that inhabit affected waters. To
understand the effects of low dissolved oxygen stress on oysters, hatchery-reared
oysters were placed in cages and deployed along with continuously recording
environmental data sondes at a reef site in Mobile Bay, AL that typically
experiences low oxygen conditions. To detect and measure sublethal stress, we
measured growth and survival of oysters as well as expression of three
biomarkers, heat shock protein 70 (HSP70), hypoxia inducible factor (HIF) and
phospho-p38 MAP kinase, in tissues from juvenile and adult oysters. Survival
rates were high for both juvenile and adult oysters. Expression levels of each of
the 3 isoforms of HSP 70 were negatively correlated to dissolved oxygen (DO)
concentrations, suggesting that HSP 70 is useful to quantify sublethal effects of
DO stress. Results for HIF and phospho-p38 MAP kinase were inconclusive. Test
deployments of oysters to assess expression of HSP 70 relative to environmental
conditions will be useful, in addition to measuring abiotic factors, to identify
appropriate sites for restoration, particularly to capture negative effects of
habitat quality on biota before lethal impacts are incurred.
PMID- 25116468
TI - Diruthenium-polyyn-diyl-diruthenium wires: electronic coupling in the long
distance regime.
AB - Reported herein is a series of Ru2(Xap)4 capped polyyn-diyl compounds, where Xap
is either 2-anilinopyridinate (ap) or its aniline substituted derivatives.
Symmetric [Ru2(Xap)4](MU-C4k)[Ru2(Xap)4] (compounds 4ka (X = 3-isobutoxy) and 4kc
(X = 3,5-dimethoxy) with k = 2, 3, 4, and 5) was obtained from the Glaser
coupling reaction of Ru2(Xap)4(C2kH). Unsymmetric [Ru2(Xap)4](MU
C(4k+2))[Ru2(ap)4] (compounds 4k+2b with k = 2, 3, and 4) were prepared from the
Glaser coupling reaction between Ru2(Xap)4(C(2k+2)H) and Ru2(ap)4(C2kH). X-ray
diffraction study of compound 12c revealed both the sigmoidal topology of the
polyyn-diyl bridge and the fine structural detail about the Ru2 cores. Cyclic and
differential pulse voltammetric (CV and DPV) measurements and
spectroelectrochemical studies revealed that (i) the reduced monoanions [Ru2-C2m
Ru2](-1) (m = 4-8) belong to the Robin-Day class II mixed valent ions and (ii)
the electronic coupling between Ru2 termini depends on the length of the polyyn
diyl bridge with an attenuation constant (gamma) between 0.12 and 0.15 A(-1). In
addition, spin-unrestricted DFT calculations provide insight about the nature of
orbitals that mediate the long distance electronic coupling.
PMID- 25116467
TI - Radial glia phagocytose axonal debris from degenerating overextending axons in
the developing olfactory bulb.
AB - Axon targeting during the development of the olfactory system is not always
accurate, and numerous axons overextend past the target layer into the deeper
layers of the olfactory bulb. To date, the fate of the mis-targeted axons has not
been determined. We hypothesized that following overextension, the axons
degenerate, and cells within the deeper layers of the olfactory bulb phagocytose
the axonal debris. We utilized a line of transgenic mice that expresses ZsGreen
fluorescent protein in primary olfactory axons. We found that overextending axons
closely followed the filaments of radial glia present in the olfactory bulb
during embryonic development. Following overextension into deeper layers of the
olfactory bulb, axons degenerated and radial glia responded by phagocytosing the
resulting debris. We used in vitro analysis to confirm that the radial glia had
phagocytosed debris from olfactory axons. We also investigated whether the fate
of overextending axons was altered when the development of the olfactory bulb was
perturbed. In mice that lacked Sox10, a transcription factor essential for normal
olfactory bulb development, we observed a disruption to the morphology and
positioning of radial glia and an accumulation of olfactory axon debris within
the bulb. Our results demonstrate that during early development of the olfactory
system, radial glia play an important role in removing overextended axons from
the deeper layers of the olfactory bulb.
PMID- 25116469
TI - Tuning CO2 selective adsorption over N2 and CH4 in UiO-67 analogues through
ligand functionalization.
AB - Introducing functional groups into pores of metal-organic frameworks (MOFs)
through ligand modification provides an efficacious approach for tuning gas
adsorption and separation performances of this type of novel porous material. In
this work, two UiO-67 analogues, [Zr6O4(OH)4(FDCA)6] (BUT-10) and
[Zr6O4(OH)4(DTDAO)6] (BUT-11), with functionalized pore surfaces and high
stability were synthesized from two functional ligands, 9-fluorenone-2,7
dicarboxylic acid (H2FDCA) and dibenzo[b,d]thiophene-3,7-dicarboxylic acid 5,5
dioxide (H2DTDAO), respectively, and structurally determined by single-crystal X
ray diffraction. Notwithstanding skeleton bend of the two ligands relative to the
linear 4,4'-biphenyldicarboxylic acid in UiO-67, the two MOFs have structures
similar to that of UiO-67, with only lowered symmetry in their frameworks.
Attributed to these additional functional groups (carbonyl and sulfone,
respectively) in the ligands, BUT-10 and -11 show enhanced CO2 adsorption and
separation selectivities over N2 and CH4, in spite of decreased pore sizes and
surface areas compared with UiO-67. At 298 K and 1 atm, the CO2 uptake is 22.9,
50.6, and 53.5 cm(3)/g, and the infinite dilution selectivities of CO2/CH4 are
2.7, 5.1, and 9.0 and those of CO2/N2 are 9.4, 18.6, and 31.5 for UiO-67, BUT-10,
and BUT-11, respectively. The selectivities of CO2/CH4 and CO2/N2 are thus
enhanced 1.9 and 2.0 times in BUT-10 and 3.3 and 3.4 times in BUT-11,
respectively, on the basis of UiO-67. The adsorption mechanism of CO2 in BUT-11
has also been explored through computational simulations. The results show that
CO2 molecules locate around the sulfone groups in pore surfaces of BUT-11,
verifying at the molecular level that sulfone groups significantly increase the
affinity toward CO2 molecules of the framework. This provides thus an efficient
strategy for the design of CO2 capture materials.
PMID- 25116470
TI - Anisotropic magnetoresistance state space of permalloy nanowires with domain wall
pinning geometry.
AB - The domain wall-related change in the anisotropic magnetoresistance in L-shaped
permalloy nanowires is measured as a function of the magnitude and orientation of
the applied magnetic field. The magnetoresistance curves, compiled into so-called
domain wall magnetoresistance state space maps, are used to identify highly
reproducible transitions between domain states. Magnetic force microscopy and
micromagnetic modelling are correlated with the transport measurements of the
devices in order to identify different magnetization states. Analysis allows to
determine the optimal working parameters for specific devices, such as the
minimal field required to switch magnetization or the most appropriate angle for
maximal separation of the pinning/depinning fields. Moreover, the complete state
space maps can be used to predict evolution of nanodevices in magnetic field
without a need of additional electrical measurements and for repayable
initialization of magnetic sensors into a well-specified state.
PMID- 25116471
TI - Long-term effects of growth hormone replacement therapy on liver function in
adult patients with growth hormone deficiency.
AB - OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic
steatohepatitis (NASH) are frequently observed in patients with adult growth
hormone deficiency (AGHD) and short-term GH replacement therapy (GHRT) has
reportedly been efficacious in NAFLD and NASH. The aim of this study was to
investigate whether long-term GHRT is an effective treatment for the hepatic
comorbidities in AGHD. DESIGN: This is a retrospective observational study. We
recruited 54 consecutive hypopituitary patients with AGHD. Among them, 31
patients who had received GHRT for more than 24 months were compared with 19 age-
and sex-matched patients without GHRT. We also analyzed the long term effect of
GHRT on 14 patients diagnosed with NASH by liver biopsy. In addition, we
subdivided the GHRT group into GH-responder and GH-non-responder groups and
analyzed the factors associated with the efficacy of the treatment. RESULTS: For
a period of 24 months, the significant reduction of serum liver enzyme levels and
a fibrotic marker was observed in patients receiving GHRT compared with the
control group. Furthermore, GHRT also improved liver enzyme levels in AGHD
patients with NASH. The GH-non-responder group showed a higher proportion of
patients who gained weight during the study period. CONCLUSIONS: These results
indicate that GHRT is efficacious for improving serum liver enzyme levels for at
least 24 months in patients with AGHD. To optimize this effect, it is important
to avoid body weight gain during the treatment.
PMID- 25116472
TI - Autosomal recessive form of isolated growth hormone deficiency is more frequent
than the autosomal dominant form in a Brazilian cohort.
AB - BACKGROUND: In most studies, the autosomal dominant (type II) form of isolated
growth hormone deficiency (IGHD) has been more frequent than the autosomal
recessive (type I) form. Our aim was to assess defects in the GH1 in short
Brazilian children with different GH secretion status. SUBJECTS AND METHODS: We
selected 135 children with postnatal short stature and classified according to
the highest GH peak at stimulation tests in: severe IGHD (peak GH<=3.3 MUg/L,
n=38, all with normal pituitary magnetic resonance imaging); GH peak between 3.3
and 10 MUg/L (n=76); and GH peak >10 MUg/L (n=21). The entire coding region of
GH1 was sequenced and complete GH1 deletions were assessed by Multiplex Ligation
Dependent Probe Amplification and restriction enzyme digestion. RESULTS: Patients
with severe IGHD had a higher frequency of consanguinity, were shorter, had lower
levels of IGF-1 and IGFBP-3, and despite treatment with lower GH doses had a
greater growth response than patients with GH peak >=3.3 MUg/L. Mutations were
found only in patients with severe IGHD (GH peak<3.3 MUg/L). Eight patients had
autosomal recessive IGHD: Seven patients were homozygous for GH1 deletions and
one patient was compound heterozygous for a GH1 deletion and the novel c.171+5G>C
point mutation in intron 2, predicted to abolish the donor splice site. Only one
patient, who was heterozygous for the c.291+1G>T mutation located at the
universal donor splice site of intron 3 and predicts exon 3 skipping, had an
autosomal dominant form. CONCLUSION: Analysis of GH1 in a cohort of Brazilian
patients revealed that the autosomal recessive form of IGHD was more common than
the dominant one, and both were found only in severe IGHD.
PMID- 25116476
TI - Activated-ester-type photocleavable crosslinker for preparation of
photodegradable hydrogels using a two-component mixing reaction.
AB - Photodegradable hydrogels have emerged as powerful platforms for studying and
directing cellular behavior in a spatiotemporally controlled manner.
Photodegradable hydrogels have previously been formed by free radical
polymerizations, Michael-type addition reactions, and orthogonal click reactions.
Here, an ester-activated photocleavable crosslinker is presented for preparing
photodegradable hydrogels by means of a one-step mixing reaction between the
crosslinker and a biocompatible polymer containing amino moieties (amino
terminated tetra-arm poly(ethylene glycol) or gelatin). It is demonstrated that
photodegradable hydrogels micropatterned by photolithography can be used to
culture cells with high viability and proliferation rates. The resulting
micropatterned cell-laden structures can potentially be used to create 3D
biomaterials for various tissue-engineering applications.
PMID- 25116477
TI - Controlling the enzymatic digestion of lipids using hybrid nanostructured
materials.
AB - Solid nanoparticle-lipid hybrids have been engineered by using spray drying to
assemble monodisperse hydrophilic silica nanoparticles and submicron lipid
(triglyceride) emulsions together into composite microparticles, which have
specific activity toward enzymes. The influence of silica particle size (100-1000
nm) and emulsifier type (anionic and cationic) on the three-dimensional structure
of the composite particles was investigated. The nanostructure of the hybrid
particles, which is controlled by the size of the voids between the closely
packed silica particles, plays a critical role in lipase action and hence lipid
digestion kinetics. Confining lipid droplets within the nanostructured silica
aggregates led to 2- to 15-fold enhanced rate of lipolysis in comparison with
dispersed coarse oil droplets. The composite particles were tailored to enhance,
retain or sustain the lipolysis kinetics of submicron lipid emulsions. The
presence of repulsive nanoparticle-droplet interactions favored aqueous
redispersion and fast lipolysis of the hybrid composite materials, while
attractive interactions hindered redispersion and delayed lipolysis of the
confined lipid droplets. Such hybrid nanomaterials can be exploited to control
the gastrointestinal enzymatic action and promisingly form the basis for the next
generation of foods and medicines.
PMID- 25116473
TI - Fgfr1 inactivation in the mouse telencephalon results in impaired maturation of
interneurons expressing parvalbumin.
AB - Fibroblast growth factors (Fgfs) and their receptors (Fgfr) are expressed in the
developing and adult CNS. Previous studies demonstrated a decrease in cortical
interneurons and locomotor hyperactivity in mice with a conditional Fgfr1
deletion generated in radial glial cells during midneurogenesis
(Fgfr1(f/f);hGfapCre+). Here, we report earlier and more extensive inactivation
of Fgfr1 in neuroepithelial cells of the CNS (Fgfr1(f/f);NesCre+). Similar to
findings in Fgfr1(f/f);hGfapCre+ mice, parvalbumin positive (PV+) cortical
interneurons are also decreased in the neocortex of Fgfr1(f/f);NesCre+ mice when
compared to control littermates (Fgfr1(f/f)). Fgfr1(f/f);NesCre+ embryos do not
differ from controls in the initial specification of GABAergic cells in the
ganglionic eminence (GE) as assessed by in situ hybridization for Dlx2, Mash1 and
Nkx2. Equal numbers of GABAergic neuron precursors genetically labeled with green
fluorescent protein (GFP) were observed at P0 in Fgfr1(f/f);hGfapCre+;Gad1-GFP
mutant mice. However, fewer GFP+ and GFP+/PV+ interneurons were observed in these
mutants at adulthood, indicating that a decrease in cortical interneuron markers
is occurring postnatally. Fgfr1 is expressed in cortical astrocytes in the
postnatal brain. To test whether the astrocytes of mice lacking Fgfr1 are less
capable of supporting interneurons, we co-cultured wild type Gad1-GFP+
interneuron precursors isolated from the medial GE (MGE) with astrocytes from
Fgfr1(f/f) control or Fgfr1(f/f);hGfapCre+ mice. Interneurons grown on Fgfr1
deficient astrocytes had small soma size and fewer neurites per cell, but no
differences in cell survival. Decreased soma size of Gad67 immunopositive
interneurons was also observed in the cortex of adult Fgfr1(f/f);NesCre+ mice.
Our data indicate that astrocytes from Fgfr1 mutants are impaired in supporting
the maturation of cortical GABAergic neurons in the postnatal period. This model
may elucidate potential mechanisms of impaired PV interneuron maturation relevant
to neuropsychiatric disorders that develop in childhood and adolescence.
PMID- 25116478
TI - Physics of nanomechanical spectrometry of viruses.
AB - There is an emerging need of nanotools able to quantify the mechanical properties
of single biological entities. A promising approach is the measurement of the
shifts of the resonant frequencies of ultrathin cantilevers induced by the
adsorption of the studied biological systems. Here, we present a detailed
theoretical analysis to calculate the resonance frequency shift induced by the
mechanical stiffness of viral nanotubes. The model accounts for the high surface
to-volume ratio featured by single biological entities, the shape anisotropy and
the interfacial adhesion. The model is applied to the case in which tobacco
mosaic virus is randomly delivered to a silicon nitride cantilever. The
theoretical framework opens the door to a novel paradigm for biological
spectrometry as well as for measuring the Young's modulus of biological systems
with minimal strains.
PMID- 25116480
TI - Effect of pH and recombinant barley (Hordeum vulgare L.) endoprotease B2 on
degradation of proteins in soaked barley.
AB - Nonfermented soaking of barley feedstuff has been established as an in vitro
procedure prior to the feeding of pigs as it can increase protein digestibility.
In the current study, two feed cultivars of barley (Finlissa and Zephyr) were
soaked in vitro either nonbuffered or buffered at pH 3.6 and 4.3. Solubilized and
degraded proteins evaluated by biuret, SDS-PAGE, and differential proteomics
revealed that pH 4.3 had the greatest impact on both solubilization and
degradation. In order to boost proteolysis, the recombinant barley endoprotease
B2 (rec-HvEP-B2) was included after 8 h using the pH 4.3 regime. Proteolysis
evaluated by SDS-PAGE and differential proteomics confirmed a powerful effect of
adding rec-HvEP-B2 to the soaked barley, regardless of the genotype. Our study
addresses the use of rec-HvEP-B2 as an effective feed enzyme protease. HvEP-B2
has the potential to increase the digestibility of protein in the pig, either
supplied as recombinant additive or as possible new selection criterion in barley
breeding.
PMID- 25116479
TI - Porcine epidemic diarrhea virus RNA present in commercial spray-dried porcine
plasma is not infectious to naive pigs.
AB - Porcine epidemic diarrhea virus emerged in North America in April 2013 and has
since been identified in 30 U.S. States, Canada and Mexico. The rapid spread of
PEDV has raised concerns about the role of feed and particularly pork-by-product
components such as spray-dried porcine plasma (SDPP) in PEDV transmission. The
aim of this study was to determine the infectivity of PEDV RNA present in
commercial SDPP. Specifically, 40 3-week-old PEDV naive pigs were randomly
assigned to one of five treatment groups. At day post inoculation (dpi) 0, NEG
CONTROL pigs were sham-inoculated, PEDV-CONTROL pigs received cell culture
propagated PEDV, and SDPP-CONTROL pigs were switched to a diet with 5% SDPP
containing 5.1+/-0.1 log10 PEDV RNA copies/g. To evaluate a potential positive
effect of anti-PEDV antibodies in SDPP on PEDV challenge, four days prior to PEDV
challenge the pigs in the SDPP-PEDV group were switched to and remained on a 5%
SDPP diet through dpi 28. Another group, EGG-PEDV, was orally administered a
commercial egg-derived liquid PEDV globulin product from dpi -4 through 6. All
PEDV-CONTROL pigs began shedding PEDV in feces by dpi 3 and seroconverted between
dpi 7 and 14, whereas pigs in NEG-CONTROL and SDPP-CONTROL groups remained PEDV
RNA negative and did not seroconvert to PEDV for the study duration. This
indicates no evidence of infectivity of the PEDV RNA in the SDPP lot utilized.
Furthermore, under the study conditions SDPP or egg-derived liquid PEDV globulin
addition did not significantly alter PEDV-shedding or overall disease course
after experimental challenge.
PMID- 25116481
TI - Safety, pharmacokinetic, and positron emission tomography evaluation of serotonin
and dopamine transporter occupancy following multiple-dose administration of the
triple monoamine reuptake inhibitor BMS-820836.
AB - RATIONALE: BMS-820836 is a novel antidepressant that selectively inhibits the
reuptake of serotonin, norepinephrine, and dopamine. OBJECTIVE: This Phase I
study assessed safety, tolerability, and pharmacokinetics of multiple daily doses
of BMS-820836 in healthy subjects. Central serotonin transporter (SERT) and
dopamine transporter (DAT) occupancy were assessed using positron emission
tomography and [(11)C]MADAM or [(11)C]PE2I, respectively. METHODS: Fifty-seven
healthy volunteers were enrolled in this double-blind, placebo-controlled,
ascending multiple-dose study (ClincalTrials.gov identifier: NCT00892840). Eight
participants in seven dose cohorts received oral doses of BMS-820836 (0.1-4 mg)
or placebo for 14 days to assess safety, tolerability, and pharmacokinetics.
Additionally, SERT and DAT occupancies were evaluated in 4-8 subjects per cohort
at 8 h post-dose on Day 10 and 24 h post-dose on Day 15 at anticipated steady
state conditions. RESULTS: Most adverse events were mild to moderate; there were
no serious safety concerns. Median maximum concentrations of BMS-820836 were
observed at 4.0-5.5 h post-dose; estimated elimination half-life was 44-74 h.
About 80 % striatal SERT occupancy was achieved after multiple doses of 0.5 mg
BMS-820836 at both 8 and 24 h post-dose. Striatal DAT occupancy ranged between 14
% and 35 % at 8 h post-dose with a slight decline at 24 h post-dose. CONCLUSIONS:
Multiple daily doses of up to 4 mg BMS-820836 appeared to be generally safe and
well tolerated in a healthy population. SERT and DAT occupancies were in a range
associated with therapeutic efficacy of antidepressants. Together with the
pharmacokinetic profile of BMS-820836, the occupancy data support once-daily
administration.
PMID- 25116484
TI - Research on the infiltration processes of lawn soils of the Babao River in the
Qilian Mountain.
AB - Using a Guelph Permeameter, the soil water infiltration processes were analyzed
in the Babao River of the Qilian Mountain in China. The results showed that the
average soil initial infiltration and the steady infiltration rates in the
upstream reaches of the Babao River are 1.93 and 0.99 cm/min, whereas those of
the middle area are 0.48 cm/min and 0.21 cm/min, respectively. The infiltration
processes can be divided into three stages: the rapidly changing stage (0-10
min), the slowly changing stage (10-30 min) and the stabilization stage (after 30
min). We used field data collected from lawn soils and evaluated the performances
of the infiltration models of Philip, Kostiakov and Horton with the sum of
squared error, the root mean square error, the coefficient of determination, the
mean error, the model efficiency and Willmott's index of agreement. The results
indicated that the Kostiakov model was most suitable for studying the
infiltration process in the alpine lawn soils.
PMID- 25116482
TI - Cognitive judgment bias in the psychostimulant-induced model of mania in rats.
AB - RATIONALE: Animal models of mania lack genuine cognitive parameters. The present
gold standard of mania models, amphetamine-induced hyperlocomotion, is rather
unspecific and does not necessarily target its cardinal symptoms. Therefore,
alternative behavioral markers that are sensitive to stimulants are required.
OBJECTIVES: In the present study, by combining the psychostimulant-induced model
of mania in rodents with the recently developed ambiguous-cue interpretation
(ACI) tests, we investigated the effects of chronic administration of D
amphetamine and cocaine on the cognitive judgment bias of rats. METHODS: To
accomplish this goal, in two separate experiments, previously trained animals
received chronic, daily injections of either D-amphetamine (2 mg/kg) or cocaine
(10 mg/kg) for 2 weeks and were subsequently tested with the ACI procedure.
RESULTS: Chronic treatment with both psychostimulants did not make rats more
"optimistic." CONCLUSIONS: The results are discussed in terms of behavioral and
pharmacological actions of the tested compounds and their implications for
modeling mania in animals.
PMID- 25116485
TI - Retainment of the antimicrobial agent triclosan in a septic tank.
AB - Laboratory experiments were conducted to investigate the fate of the
antimicrobial agent triclosan (TCS) in a conventional septic tank. The main
mechanism of TCS removal from wastewater was identified to be rapid TCS sorption
to suspended particles followed by settling of these particles to the bottom of
the septic tank. Sorption to particles was completed within minutes while the
settling took several days. Therefore, in a septic tank the removal of TCS from
wastewater is mainly determined by the removal of suspended particles by
sedimentation. Over 5 days of hydraulic residence time the initial dissolved TCS
concentration of 100 MUg L(-1) was reduced by 87 +/- 8%. During the first 24
hours, 66-86% of all removed TCS was retained, whereas during the remainder of
the experiment a slight but steady decrease in TCS concentration was observed.
This was most likely caused by TCS diffusion and its subsequent sorption onto the
septic sludge.
PMID- 25116483
TI - Reduced dopamine release in the nucleus accumbens core of adult rats following
adolescent binge alcohol exposure: age and dose-dependent analysis.
AB - RATIONALE: Alcohol use in adolescence is one of the most significant predictors
of alcohol dependence in adulthood, yet the neurochemical mechanisms underlying
this heightened vulnerability remain unknown. Whereas research has focused on
characterizing adaptations in the mesolimbic dopamine (DA) system following
ethanol exposure in adolescence, whether these changes persist into adulthood has
yet to be determined. OBJECTIVES: The objective of this study is to investigate
the effects of binge-intermittent ethanol administration in adolescence (P30-50)
or early adulthood (P60-80) on DA in the nucleus accumbens (NAc) core after an
ethanol challenge in adulthood following a period of abstinence. METHODS: Male
Sprague Dawley rats (n = 160) were administered intermittent ethanol injections,
1 or 3 g/kg, intraperitoneally (i.p.) every other day for 20 days starting on
either P30 or 60. Following an ethanol-free period of either 7, 14, or 28 days,
we measured DA efflux following an ethanol challenge (3 g/kg, i.p.) using
electrochemical recording electrodes bilaterally implanted into the NAc core.
RESULTS: Moderate-dose ethanol administration (1 g/kg, i.p.) during adolescence
significantly decreased ethanol-evoked DA release in adulthood at 7 and 14 days,
but not 28 days, following pretreatment exposure compared to saline controls.
Relative to rats pretreated with ethanol in adulthood, moderate-dose ethanol in
adolescence significantly reduced DA efflux at all time points measured.
Additionally, adult rats pretreated with high dose ethanol administration (3
g/kg, i.p.) displayed significantly decreased DA compared to adolescents after 28
days of withdrawal. CONCLUSIONS: Binge-intermittent ethanol administration during
adolescence may induce age-dependent neuroadaptations in the mesolimbic DA system
compared to ethanol-treated adults during protracted ethanol withdrawal.
PMID- 25116486
TI - Effect of pH on phosphorus, copper, and zinc elution from swine wastewater
activated sludge.
AB - With the goal of reducing the amounts of phosphorus (P), copper (Cu), and zinc
(Zn) discharged from swine wastewater activated sludge treatment facilities, we
studied the elution of these elements from activated sludge at various pH values.
Sludge samples with neutral pH collected from three farms were incubated at pH
values ranging from 3 to 10. The soluble concentrations of these elements changed
dramatically with pH and were highest at pH 3. We assumed that P present in the
sludge under neutral and alkaline conditions was in insoluble form bound up with
magnesium (Mg) and calcium (Ca), because Ca and Mg also eluted from the sludge at
low pH. To clarify forms of Zn and Cu in the sludge, we performed a sequential
extraction analysis. Zinc in adsorbed, organically bound, and sulfide fractions
made up a large proportion of the total Zn. Copper in organically bound,
carbonate, and sulfide fractions made up a large proportion of the total Cu. The
soluble P concentrations were lowest at pH 9 or 10 (11-36 mg/L), the soluble Zn
concentrations were lowest at pH 8 or 9 (0.07-0.15 mg/L), and the soluble Cu
concentrations were lowest at pH 6-9 (0.2 mg/L, the detection limit).
PMID- 25116487
TI - Determination of methane yield of cellulose using different experimental setups.
AB - In this work, biochemical methane potential (BMP) tests with cellulose as a model
substrate were performed with the aid of three manually operated or conventional
experimental setups (based on manometer, water column and gas bag) and one
automated apparatus specially designed for analysis of BMP. The methane yields
were 340 +/- 18, 354 +/- 13, 345 +/- 15 and 366 +/- 5 ml CH4/g VS obtained from
experimental setups with manometer, water column, gas bag, and automatic methane
potential test system, which corresponded to a biodegradability of 82, 85, 83 and
88% respectively. The results demonstrated that the methane yields of cellulose
obtained from conventional and automatic experimental setups were comparable;
however, the methane yield obtained from the automated apparatus showed greater
precision. Moreover, conventional setups for the BMP test were more time- and
labour-intensive compared with the automated apparatus.
PMID- 25116488
TI - Cloud point extraction-flame atomic absorption spectrometry method for
preconcentration and determination of trace cadmium in water samples.
AB - A method based on cloud point extraction (CPE) separation/preconcentration of
trace cadmium (Cd) as a prior step to its determination by flame atomic
absorption spectrometry has been developed. Cadmium reacted with 8
hydroxyquinoline to form hydrophobic chelates, which were extracted into the
micelles of nonionic surfactant oligoethylene glycol monoalkyl ether (Genapol X
080) in an alkaline medium. Octanol was used to depress the cloud point of
Genapol X-080 in the extraction process. The chemical variables that affect the
CPE, such as pH of complexation reaction, amount of chelating agent, Genapol X
080 and octanol were evaluated and optimized. Under optimized conditions,
linearity was obeyed in the range of 10-500 MUg/L, with the correlation
coefficient of 0.9993. For 5 mL of sample solution, the enhancement factor was
about 20. The limit of detection and limit of quantification of the method were
0.21 and 0.63 MUg/L, respectively. The relative standard deviations (n = 6) was
3.2% for a solution containing 100 MUg/L of Cd. The accuracy of the
preconcentration system was evaluated by recovery measurements on spiked water
samples. Recoveries of spiked samples varied in the range of 94.1-103.8%.
PMID- 25116489
TI - Characterization of water pollution in drainage networks using continuous
monitoring data in the Citadel area of Hue City, Vietnam.
AB - In the Citadel area of Hue City, drainage systems that include canals and ponds
are considerable sources of fecal contaminants to inundated water during the
rainy season because canals and ponds receive untreated wastewater. It is
important to investigate the characteristics of hydraulics and water pollution in
canals and ponds. At the canals and ponds, water sampling was conducted during
dry and wet weather periods in order to evaluate fecal contamination and to
investigate changes in water pollution caused by runoff inflow. Inundated water
was also collected from streets during heavy rainfall. At the canals and ponds,
concentrations of Escherichia coli and total coliform exceeded the Vietnamese
regulation values for surface water in 23 and 24 out of 27 samples (85 and 89%),
respectively. The water samples were categorized based on the characteristics of
water pollution using cluster analysis. In the rainy season, continuous
monitoring was conducted at the canals and ponds using water depth and electrical
conductivity (EC) sensors to investigate the dynamic relationship between water
level and water pollution. It is suggested that in the canals, high EC meant
water stagnation and low EC signified river water inflow. Therefore, EC might be
a good indicator of water flow change in canals.
PMID- 25116490
TI - Removal of fluoride and arsenic by pilot vertical-flow constructed wetlands using
soil and coal cinder as substrate.
AB - This study evaluated the performance of soil and coal cinder used as substrate in
vertical-flow constructed wetlands for removal of fluoride and arsenic. Two
duplicate pilot-scale artificial wetlands were set up, planted respectively with
cannas, calamus and no plant as blank, fed with a synthetic sewage solution.
Laboratory (batch) incubation experiments were also carried out separately to
ascertain the fluoride and arsenic adsorption capacity of the two materials (i.e.
soil and coal cinder). The results showed that both soil and coal cinder had
quite high fluoride and arsenic adsorption capacity. The wetlands were operated
for two months. The concentrations of fluoride and arsenic in the effluent of the
blank wetlands were obviously higher than in the other wetlands planted with
cannas and calamus. Fluoride and arsenic accumulation in the wetlands body at the
end of the operation period was in range of 14.07-37.24% and 32.43-90.04%,
respectively, as compared with the unused media.
PMID- 25116491
TI - Visualized study on the interaction between single bubbles and curved solid
surface in flotation separation process.
AB - The present study has been devoted to bubble-curved solid surface interaction in
water, which is critical to the separation of suspended particles by air
flotation. For this purpose, two particular stages of the interaction (collision
and attachment) have been examined visually using high-speed photography in a
laboratory-scale flotation column. The effects of the surface material and
surfactant concentration on these two stages have been also studied
quantitatively. The considered solid materials are the cleaned glass as
hydrophilic surface and Teflon as hydrophobic surface. The experimental results
show that the presence of surfactant significantly affects the collision and
rebound process of a gas bubble, while there is no obvious effect of the surface
material on the rebound process. An increase in surfactant concentration has been
observed to suppress the rebound number and maximal distance of the bubble from
the surface. Moreover, the three-phase contact time of the bubble is a strong
function of the surfactant concentration and surface hydrophobicity as well as of
the bubble diameter. Another important finding is that the bubble attachment is
only observed at the hydrophobic Teflon surface below the surfactant CMC
(critical micelle concentration). Results of this study are relevant for deep
understanding of the attachment mechanism and to determine the proper conditions
for a selective flotation process.
PMID- 25116492
TI - Assessment of the impact of traditional septic tank soakaway systems on water
quality in Ireland.
AB - One of the key threats to groundwater and surface water quality in Ireland is the
impact of poorly designed, constructed or maintained on-site wastewater treatment
systems. An extensive study was carried out to quantify the impact of existing
sites on water quality. Six existing sites, consisting of a traditional septic
tank and soakaway system, located in various ranges of subsoil permeabilities
were identified and monitored to determine how well they function under varying
subsoil and weather conditions. The preliminary results of the chemical and
microbiological pollutant attenuation in the subsoil of the systems have been
assessed and treatment performance evaluated, as well as impact on local surface
water and groundwater quality. The source of any faecal contamination detected in
groundwater, nearby surface water and effluent samples was confirmed by microbial
source tracking. From this, it can be seen that the transport and treatment of
percolate vary greatly depending on the permeability and composition of the
subsoil.
PMID- 25116493
TI - Removal of toluene from water by photocatalytic oxidation with activated carbon
supported Fe(3+)-doped TiO2 nanotubes.
AB - In this work, activated carbon (AC)-supported TiO2 containing 1.0% (mass percent)
of 1.0 at.% (atomic percent) Fe(3+)-doped TiO2 nanotubes (Fe-TNTs) were
successfully synthesized. The catalyst was used to effectively decompose toluene
in water under O3/UV conditions, and some properties including the morphology, X
ray photoelectron spectroscopy, X-ray diffraction patterns, specific surface area
and UV-visible diffuse reflectance spectroscopy were analyzed. A removal
efficiency of 90.7% was achieved in the presence of fresh AC-supported Fe-TNTs
calcined at 550 degrees C, with a pseudo-first-order rate constant of 0.038/min.
The removal efficiency of toluene was reduced when the catalysts were repeatedly
used, since the amount of adsorption sites of the supporting substrates
decreased. However, even after AC-supported catalyst was used four times, the
removal efficiency of toluene was still sufficient in water treatment. The
enhanced photocatalytic activity of AC-supported Fe-TNTs was related to the
synergistic effect of AC adsorption and Fe-TNTs photocatalytic ozonation. The
water from a petrochemical company in China was used to obtain the removal
efficiency of the pollutants, and the toluene and total organic carbon removal
efficiencies were 69.9% and 58.3%, respectively.
PMID- 25116494
TI - Study of competitive adsorption of acid dyes on magnetic quaternary chitosan
salt.
AB - Magnetic quaternary chitosan salt CS/EPTAC/Fe3O4 was used for the removal of acid
red 1 (AR1), xylenol orange (XO) and alizarin red (AR) in single, binary and
ternary systems. In the single system, the maximal adsorption capacity was 781.55
for AR1, 537.40 for XO and 992.61 mg g(-1) for AR at pH 3.0 and 25 degrees C.
The adsorption kinetics of the three dyes followed the pseudo-second-order model.
In the multicomponent system, preferential adsorption was observed for AR at low
adsorbent quantities due to the small size of the molecule. When the adsorbent
amount was greater, AR1 was adsorbed first because of the greater number of
sulfonic acid roots. In the entire adsorption process, XO always adsorbed most
slowly.
PMID- 25116495
TI - Development of a down-flow hanging sponge reactor for the treatment of low
strength sewage.
AB - The process performance of a down-flow hanging sponge (DHS) reactor for treating
low strength sewage (biochemical oxygen demand (BOD) 20-50 mg/L) was investigated
in Bangkok, Thailand. The hydraulic retention time (HRT) was set at 4 h during
the start-up period and was reduced to 1.5 h in a stepwise manner. Throughout the
300-day operational period, the DHS reactor shows high performance with respect
to the removal of total suspended solid (>90% total suspended solid removal
efficiency). No clogging of sponge media was observed in response to the self
digestion phenomena of the biofilm. At a HRT of 1.5 h, the BOD removal efficiency
was sufficiently high (about 85%). The pathogen Escherichia coli and other
coliform bacteria were removed almost completely as well (removal was 99.4% and
98.1%, respectively). Regarding the retained sludge activity measurement, the
nitrite oxidation rate was higher than the ammonium oxidation rate (0.031 and
0.022 gram of nitrogen per gram of volatile suspended solids per day,
respectively). In the 300 days of operation, the amount of excess sludge
production was negligible. Thus, no sludge treatment system is required.
Introduction of the DHS system in developing countries is recommended because
this system requires a relatively small area, and has low electricity consumption
and operation costs.
PMID- 25116496
TI - Adsorption of hexavalent chromium onto organic bentonite modified by the use of
iron(III) chloride.
AB - The adsorption of hexavalent chromium (Cr(VI)) was improved by using organic
bentonite (OB) modified with iron(III) chloride. The adsorption mechanisms and
characteristics of OB and organic bentonite modified by FeCl3 (FMOB) were studied
by using X-ray diffraction, Fourier transform infrared spectroscopy, scanning
electron microscopy, and energy dispersive X-ray spectroscopy (EDS). It was found
that hydroxyl-iron replaced some of the calcium and magnesium contained in the
FMOB, but no significant change in its structure was shown even though the
adsorption experiments proved that FMOB had a better Cr(VI) adsorption ability
compared to OB. The coated material was prepared by mixing FMOB and 4A molecular
sieves in a coated pot for the adsorption experiments in the test column. The
relevant results showed that the adsorption of the coated material retained its
high adsorption ability and maintained that ability after desorption and
regeneration, which implied a potential for further application.
PMID- 25116497
TI - Impacts of urbanization on river system structure: a case study on Qinhuai River
Basin, Yangtze River Delta.
AB - Stream structure is usually dominated by various human activities over a short
term. An analysis of variation in stream structure from 1979 to 2009 in the
Qinhuai River Basin, China, was performed based on remote sensing images and
topographic maps by using ArcGIS. A series of river parameters derived from river
geomorphology are listed to describe the status of river structure in the past
and present. Results showed that urbanization caused a huge increase in the
impervious area. The number of rivers in the study area has decreased and length
of rivers has shortened. Over the 30 years, there was a 41.03% decrease in river
length. Complexity and stability of streams have also changed and consequently
the storage capacities of river channels in intensively urbanized areas are much
lower than in moderately urbanized areas, indicating a greater risk of floods.
Therefore, more attention should be paid to the urban disturbance to rivers.
PMID- 25116498
TI - Removal of hexavalent chromium from aqueous solution using exfoliated
polyaniline/montmorillonite composite.
AB - Exfoliated polyaniline/montmorillonite (PANI/MMT) composites with nanosheet
structure were successfully prepared by in situ chemical oxidation polymerization
with MMT platelets as the scaffold. Amphoteric polymer, (2
methacryloyloxyethyl)trimethyl ammonium chloride and methacrylate acid copolymer,
was used to modify montmorillonite and a large number of carboxylic acids were
introduced on the surface of the clay platelets, which can be used as a dopant of
PANI and play a 'bridge' role to combine PANI with clay. Adsorption experiments
were carried out to study the effects of pH, contact time, Cr(VI) concentration,
adsorbent dose and temperature. The adsorption of Cr(VI) on the PANI/MMT was
highly pH dependent and the adsorption kinetics followed a pseudo-second-order
model. The Langmuir isothermal model described the adsorption isotherm data well
and the maximum adsorption capacity increased with the increase in temperature.
Thermodynamic investigation indicated that the adsorption process is spontaneous,
endothermic and marked with an increase in randomness at the adsorbent - liquid
interface. The maximum adsorption capacity of the PANI/MMT composites for Cr(VI)
was 308.6 mg/g at 25 degrees C. The excellent adsorption characteristic of
exfoliated PANI/MMT composites will render it a highly efficient and economically
viable adsorbent for Cr(VI) removal.
PMID- 25116499
TI - Migration and transformation behavior of volatile phenol in the vadose zone.
AB - Research on the migration and transformation of phenol with space and temporal
variability in the vadose zone is hindered by monitoring technology in field
experiments. Four column experiments were conducted to investigate the effect of
porous media size, volatilization, biological effects, and oxidation on the
transport of phenol in the vadose zone. The initial inflow phenol concentration
of each column was 500 mg/L, and the final outflow concentrations were 0, 348,
240, and 365 mg/L, More than 90% of reduction of phenol concentration occurred at
the top of the simulation column. Results show that volatilization and oxidation
are the main factors that could lead to the decrease of phenol concentration in
an open system. However, these two processes cannot be accurately separated. The
migration rate of phenol was larger in coarse sands (6.06 cm/d) than in fine
sands (4.55 cm/d). Phenol biodegradation did not occur under experimental
conditions. However, mercury (as biological inhibitor) could react with phenol to
generate a mercury-phenol complex, which could lead to the reduction of phenol
concentration to 21.6% in the simulation experiment.
PMID- 25116500
TI - A novel control strategy for efficient biological phosphorus removal with carbon
limited wastewaters.
AB - This work shows the development and the in silico evaluation of a novel control
strategy aiming at successful biological phosphorus removal in a wastewater
treatment plant operating in an A(2)/O configuration with carbon-limited
influent. The principle of this novel approach is that the phosphorus in the
effluent can be controlled with the nitrate setpoint in the anoxic reactor as
manipulated variable. The theoretical background behind this control strategy is
that reducing nitrate entrance to the anoxic reactor would result in more organic
matter available for biological phosphorus removal. Thus, phosphorus removal
would be enhanced at the expense of increasing nitrate in the effluent (but
always below legal limits). The work shows the control development, tuning and
performance in comparison to open-loop conditions and to two other conventional
control strategies for phosphorus removal based on organic matter and metal
addition. It is shown that the novel proposed strategy achieves positive nutrient
removal results with similar operational costs to the other control strategies
and open-loop operation.
PMID- 25116501
TI - Evaluation of biotreatability of ionic liquids in aerobic and anaerobic
conditions.
AB - The aim of our study was to set up an approach for reliable biotreatability
assessment of ionic liquids (ILs). As a case study, two different ILs were
selected: pyridinium-based 1-butyl-3-methylpyridinium dicyanamide ([bmpyr][dca])
and imidazolium-based 1-butyl-3-methylimidazole tetrafluoroborate ([bmim][BF4]).
Toxicity in aerobic conditions was determined by measurement of inhibition of
oxygen consumption by activated sludge, while their biodegradability was
calculated from measurements of oxygen consumption and dissolved organic carbon
elimination. For their biotreatability in anaerobic conditions, the method with
measurement of biogas production has been employed comparing flocculent and
granular sludge. Both ILs were less toxic and more biodegradable in anaerobic
conditions. IL [bmpyr][dca] was not toxic to granular sludge up to 742 mg L(-1)
and it even has been degraded at this concentration in the presence of easily
degradable glucose. Flocculent sludge was completely inhibited at the lower
concentration of 318 mg L(-1), but it degraded by 44% at 106 mg L(-1) in the
presence of glucose, indicating the appearance of cometabolism. IL [bmim][BF4]
was less toxic but also resistant to biodegradation in anaerobic conditions. It
degraded via cometabolism 21% at 1,452 mg L(-1). It has been concluded that any
assessment of biotreatability of ILs should include parallel determination in
aerobic and anaerobic conditions.
PMID- 25116502
TI - Tertiary treatment for wastewater reuse based on the Daphnia magna filtration -
comparison with conventional tertiary treatments.
AB - Tertiary treatments are required to permit safe reuse of wastewater. The
performance of a new biological tertiary treatment based on the filtration by a
population of Daphnia magna was studied and compared with the performance of
other conventional tertiary treatments such as coagulation-flocculation, settling
tank, disc filtration, sand filtering and ultraviolet (UV) light. The analysis
was based on the efficiency in the particle removal and Escherichia coli
inactivation. The Daphnia magna treatment reduced the concentration of particles
with diameters below 30 MUm by 35%, depending on abiotic parameters such as water
temperature and the hydraulic retention time (HRT). The Daphnia magna filtration
increased with water temperature for water temperatures >20 degrees C, while it
remained constant for water temperatures <20 degrees C. Lower HRTs induced the
growth of the Daphnia magna population, maintaining the same water quality.
Furthermore, the Daphnia magna treatment inactivated E. coli in 1.2 log units.
This inactivation was six times larger than that obtained by the conventional
macrofiltration systems analyzed, although lower than the inactivation attained
by UV light, which ranged between 1.5 and 4 log units.
PMID- 25116503
TI - Investigation of initial pH effects on growth of an oleaginous microalgae
Chlorella sp. HQ for lipid production and nutrient uptake.
AB - Using microalgae for synchronous biodiesel production and wastewater treatment is
a promising technology. The growth, lipid accumulation and nutrient uptake
characteristics of an oleaginous microalga Chlorella sp. HQ were evaluated at
different initial pH from 5.0 to 11.0. The pH values changed towards neutrality
and ended in the range 6.0-9.0 without artificial control. The alkalinity change
before 8 days was in accordance with pH changing. The alkalinity increase after 8
days might be due to the nitrate consumption, CO2 absorption and the algal
release at stationary phases. The algal maximal cell density and population
growth rate increased with initial pH values while the specific growth rate kept
high without significant difference. After 30 days, the maximal algal lipid yield
reaching 167.5 mg . L(-1) occurred at initial pH of 7.0 and the triacylglycerols
content was significantly enhanced to 63.0% at initial pH of 5.0 but with a peak
of 54.4 mg . L(-1) at initial pH of 9.0. Furthermore, nutrients were taken up by
the alga obviously at all initial pH values. The total nitrogen (TN) and total
phosphorus (TP) uptake efficiencies in neutral/alkalic circumstances were larger
than that in acid circumstance. The TN and TP were removed by 87.77% and 92.05%,
respectively, at initial pH of 7.0.
PMID- 25116504
TI - N2O emissions from secondary clarifiers and their contribution to the total
emissions of the WWTP.
AB - Recent studies have indicated that the emissions of nitrous oxide, N2O,
constitute a major part of the carbon footprint of wastewater treatment plants
(WWTPs). Denitrification occurring in the secondary clarifier basins has been
observed by many researchers, but until now N2O emissions from secondary
clarifiers have not been widely reported. The objective of this study was to
measure the N2O emissions from secondary clarifiers and weigh the portion they
could represent of the overall emissions at WWTPs. Online measurements over
several days were carried out at four different municipal WWTPs in Finland in
cold weather conditions (March) and in warm weather conditions (June-July). An
attempt was made to define the conditions in which N2O emissions from secondary
clarifiers may occur. It was evidenced that large amounts of N2O can be emitted
from the secondary clarifiers, and that the emissions have long-term variation.
It was assumed that part of the N2O released in secondary clarification was
originally formed in the activated sludge basin. The emissions from secondary
clarification thus seem to be dependent on conditions of the nitrification and
denitrification accomplished in the denitrification-nitrification process and on
the amount of sludge stored in the secondary clarifiers.
PMID- 25116505
TI - Simultaneous autotrophic denitrification and nitrification in a low-oxygen
reaction environment.
AB - The occurrence of autotrophic denitrification and nitrification activities by
ammonia-oxidising bacteria and nitrite-oxidising bacteria is studied in a
bioreactor system operable at low-dissolved oxygen (DO) and at variable oxygen
influx rates. At a loading of 3.6 mg NH4(+)-N/h into the bioreactor, simultaneous
autotrophic denitrification and nitrification contributed to NH4(+)-N removal
over oxygen influxes of 2-14 mg O2/h and DO <0.5 mg/L. The maximum autotrophic
denitrification (or total-N removal) rates were achieved in a narrow oxygen
influx band of 3-5 mg O2/h, where it accounted for up to 36% of NH4(+)-N removal.
At oxygen influx >16 mg O2/h and DO >2 mg/L, autotrophic denitrification ceases
and roughly 90% of feed NH4(+)-N is oxidised to NOX(-)-N. The stability of total
effluent chemical oxygen demand (COD) over the range of oxygen influxes tested
confirms the absence of heterotrophic denitrification in the bioreactor. The long
solids residence time of the stable biomass zone (21 days) led to production of
effluent COD as a result of cell decay, and thus effluent COD was used to
calculate more accurately the mean cell residence time.
PMID- 25116506
TI - Treatment of textile wastewaters using Eutectic Freeze Crystallization.
AB - A water treatment process needs to recover both water and other useful products
if the process is to be viewed as being financially and environmentally
sustainable. Eutectic Freeze Crystallization (EFC) is one such sustainable water
treatment process that is able to produce both pure ice (water) and pure salt(s)
by operating at a specific temperature. The use of EFC for the treatment of water
is particularly useful in the textile industry because ice crystallization
excludes all impurities from the recovered water, including dyes. Also, EFC can
produce various salts with the intention of reusing these salts in the process.
This study investigated the feasibility of EFC as a treatment method for textile
industry wastewaters. The results showed that EFC can be used to convert 95% of
the wastewater stream to pure ice (98% purity) and sodium sulfate.
PMID- 25116507
TI - Evaluation of non-thermal effects by microwave irradiation in hydrolysis of waste
activated sludge.
AB - The activation energy (Ea) for waste-activated sludge (WAS) hydrolysis was
compared between microwave irradiation (MW) and conventional heating (CH) methods
to evaluate the non-thermal effect of MW. The microwave-assisted hydrolysis of
WAS was assumed to follow the first-order kinetics on the basis of volatile
suspended solids (VSS) conversion to soluble chemical oxygen demand (SCOD) for
different initial VSS concentrations. By comparing the VSS decrement and the SCOD
increment between MW and CH at different absolute temperatures of 323, 348 and
373 K, the average ratio of VSS conversion to SCOD was determined to range from
1.42 to 1.64 g SCOD/g VSS. These results corresponded to the theoretical value of
1.69 g SCOD/g VSS based on the assumption that the molecular formula of sludge
was C10H19O3N. Consequently, the Ea of the MW-assisted WAS hydrolysis was much
lower than that of CH for the same temperature conditions. The non-thermal effect
of MW in the hydrolysis of WAS could be identified with the lower Ea than that of
CH.
PMID- 25116508
TI - A health risk assessment of reclaimed municipal wastewater for industrial and
miscellaneous use.
AB - The study evaluated the safety of reclaimed water using health risk assessment
and biotoxicity tests. The reclaimed water was produced from reverse osmosis and
used in industrial and miscellaneous purposes. The health risk assessment was
conducted based on the concentrations of detectable pollutants in reclaimed water
in a hypothetical scenario. The estimated carcinogenic and non-carcinogenic risks
are lower than the generally accepted level. Biotoxicity evaluation included
three genotoxicity tests, a chronic toxicity test using medaka fishes, and a
subchronic toxicity test using mice. The reclaimed water is not genetically
toxic, and does not cause significant chronic effects on these model organisms.
These results confirm the safety of using reclaimed water from municipal
wastewater treatment plants.
PMID- 25116510
TI - Carborane functionalization of the aromatic network in chemically-synthesized
graphene.
AB - The conjugated aromatic system of graphene was used to trap the reactive, boron
rich 1,2-carborane cluster. Functionalization of the graphene surface was
confirmed by solid-state MAS (11)B NMR spectroscopy and quantified by X-ray
photoelectron spectroscopy. This work represents the first confirmed example of
direct functionalization of a graphene lattice with carboranes.
PMID- 25116509
TI - Examining the sustainment of the Adolescent-Community Reinforcement Approach in
community addiction treatment settings: protocol for a longitudinal mixed method
study.
AB - BACKGROUND: Although evidence-based treatments are considered the gold standard
for clinical practice, it is widely recognized that evidence-based treatment
implementation in real world practice settings has been limited. To address this
gap, the federal government provided three years of funding, training and
technical assistance to 84 community-based treatment programs to deliver an
evidence-based treatment called the Adolescent-Community Reinforcement Approach
(A-CRA). Little is known about whether such efforts lead to long-term A-CRA
sustainment after the initial funding ends. METHODS/DESIGN: We will use a
longitudinal mixed method data analytic approach to characterize sustainment over
time and to examine the factors associated with the extent to which A-CRA is
sustained. We will use implementation data collected during the funding period
(e.g., organizational functioning, staff certification rates and penetration) and
supplement it with additional data collected during the proposed project period
regarding implementation quality and the hypothesized predictors of sustainment
(i.e., inner and outer contextual variables) collected over three waves from 2013
to 2015 representing program sustainment up to five years post-initial funding.
DISCUSSION: Gaining a better understanding of the factors that influence the
evidence-based treatment sustainment may lead to more effective dissemination
strategies and ultimately improve the quality of care being delivered in
community-based addiction treatment settings.
PMID- 25116511
TI - Liposomes in topical ophthalmic drug delivery: an update.
AB - Topical route of administration is the most commonly used method for the
treatment of ophthalmic diseases. However, presence of several layers of
permeation barriers starting from the tear film till the inner layers of cornea
make it difficult to achieve the therapeutic concentrations in the target tissue
within the eye. In order to circumvent these barriers and to provide sustained
and targeted drug delivery, tremendous advances have been made in developing
efficient and safe drug delivery systems. Liposomes due to their unique structure
prove to be extremely beneficial drug carriers as they can entrap both the
hydrophilic and hydrophobic drugs. The conventional liposomes had several
drawbacks particularly their tendency to aggregate, the instability and leakage
of entrapped drug and susceptibility to phagocytosis. Due to this reason, for a
long time, liposomes as drug delivery systems did not attract much attention of
researchers and clinicians. However, over recent years development of new
generation liposomes has opened up new approaches for targeted and sustained drug
delivery using liposomes and has rejuvenated the interest of researchers in this
field. In this review we present a summary of current literature to understand
the anatomical and physiological limitation in achieving adequate ocular
bioavailability of topically applied drugs and utility of liposomes in overcoming
these limitations. The recent developments related to new generation liposomes
are discussed.
PMID- 25116513
TI - A functionalized, ethynyl-decorated, tetracobalt(III) cubane molecular catalyst
for photoinduced water oxidation.
AB - A new tetracobalt(III) cubane 1, carrying functionalized peripheral ethynyl
groups, was prepared. Cubane 1 catalyses photoinduced water oxidation, indicating
that the ethynyl groups do not negatively affect the catalytic properties of the
Co cubane assembly. In contrast, the quantum yield for water oxidation (0.36) is
significantly increased with respect to the prototype, simplest species.
PMID- 25116512
TI - Enhanced transdermal delivery of luteolin via non-ionic surfactant-based vesicle:
quality evaluation and anti-arthritic assessment.
AB - Luteolin (LUT) is a promising molecule with potential anti-arthritic activity.
This investigation presents formulation and evaluation of niosomal transgel for
enhanced transdermal delivery of LUT. Different non-ionic surfactants and vesicle
compositions were employed for preparation of niosomes. The vesicle size analysis
showed that all vesicles were in the range from 534.58 to 810.22 nm which
favoured efficient transdermal delivery. The entrapment of LUT in vesicle was
found to be higher in all surfactant. The developed formulation was proved
significantly superior in terms of amount of drug permeation with an enhancement
ratio of 2.66 when compared to a control formulation. The in vivo bioactivity
studies revealed that the prepared niotransgel formulation of LUT was able to
provide good anti-arthritic activity and the results were comparable to standard
(diclofenac gel for anti-arthritic and analgesic). Finally, the results were
confirmed through radiological analysis which proved that the prepared
niotransgel was effectively able to treat arthritis and results were comparable
with the standard formulation.
PMID- 25116515
TI - Continuation of NHS Pay Review body benefits all.
AB - The prospect of yet another year in which most nurses' standard of living will
fall because the English government is too mean to fund a pay rise could hardly
be more depressing. Last week's announcement by the Treasury that nurses will not
receive a cost-of-living pay award next year - only a 1 per cent one-off payment
if they are at the top of their pay band - demonstrates the lack of respect
ministers have for the profession.
PMID- 25116514
TI - Solution and crystal structure of BA42, a protein from the Antarctic bacterium
Bizionia argentinensis comprised of a stand-alone TPM domain.
AB - The structure of the BA42 protein belonging to the Antarctic flavobacterium
Bizionia argentinensis was determined by nuclear magnetic resonance and X-ray
crystallography. This is the first structure of a member of the PF04536 family
comprised of a stand-alone TPM domain. The structure reveals a new topological
variant of the four beta-strands constituting the central beta-sheet of the
alphabetaalpha architecture and a double metal binding site stabilizing a pair of
crossing loops, not observed in previous structures of proteins belonging to this
family. BA42 shows differences in structure and dynamics in the presence or
absence of bound metals. The affinity for divalent metal ions is close to that
observed in proteins that modulate their activity as a function of metal
concentration, anticipating a possible role for BA42.
PMID- 25116516
TI - 100 years to the day: candlelit vigil at Westminster Abbey.
AB - A ceremony attended by nurses marking the centenary of the outbreak of the first
world war was held at Westminster Abbey last week.
PMID- 25116517
TI - Stafford Hospital witness to advise NHS Freedom to Speak Up review.
AB - The nurse who exposed appalling treatment of patients at Stafford Hospital has
been enlisted as an adviser to a major review into NHS whistleblowing.
PMID- 25116519
TI - Pay rise 'a political issue' as review body ignored.
AB - The government is refusing to revisit its decision to deny 70 per cent of nurses
a 1 per cent cost of living pay rise next April - despite the looming threat of
industrial action by a number of health unions.
PMID- 25116520
TI - Nurses in the front line of cuts at HEE.
AB - Nearly one third of senior Health Education England (HEE) posts that will be axed
to reduce costs are held by nurses, Nursing Standard has learned.
PMID- 25116521
TI - Ebola death toll rises in Africa with at least 14 nurses among the dead.
AB - At least 14 nurses are among 80 healthcare workers who have died from an outbreak
of the Ebola virus spreading across West Africa, declared an international public
health emergency last week by the World Health Organization (WHO).
PMID- 25116522
TI - Nurse admits to falsifying records.
AB - A nurse has pleaded guilty to nine counts of wilful neglect while working at the
Princess of Wales Hospital in Bridgend, Wales.
PMID- 25116524
TI - Medication patch may help people with schizophrenia.
AB - Mental health research nurses are recruiting patients to take part in an ongoing
landmark trial to test an antipsychotic medication patch to treat schizophrenia.
PMID- 25116525
TI - Staff seek funds in NHS version of Dragons' Den.
AB - Nurses and healthcare assistants pitched ideas to improve care in a Dragons' Den
style event at Northern Lincolnshire and Goole NHS Foundation Trust last week.
PMID- 25116526
TI - Grouping diabetes checks could confuse score and reward process.
AB - Diabetes nurses have questioned whether GP practices will have the staff capacity
to carry out eight health checks on diabetes patients recommended by the National
Institute for Care and Health Excellence (NICE).
PMID- 25116527
TI - Volunteer healthcare staff set off to Gaza.
AB - Nurses are among a team of 14 health professionals who have gone to Gaza as part
of a humanitarian NHS mission.
PMID- 25116528
TI - Staffing shortfalls remain an issue at many trusts in special measures.
AB - Five trusts that must remain in special measures for another six months have
nurse shortages and inadequate leadership that pose a threat to public safety,
according to a report by health regulators.
PMID- 25116530
TI - Niece visits library that honours nurse killed on WW1 front line.
AB - The niece of a nurse killed while caring for injured troops in the first world
war has paid an emotional visit to a medical history library named in her aunt's
memory.
PMID- 25116532
TI - Hospitals told to ban junk food and offer staff incentives to lose weight.
AB - Burgers, chips and fatty foods being served up in hospital canteens could soon
become a thing of the past, if Simon Stevens gets his way.
PMID- 25116538
TI - HIV.
AB - Essential facts [Figure: see text] HIV is a virus that weakens the immune system
and leaves people less able to fight infection. According to the National
Institute for Health and Care Excellence (NICE), an estimated 98,400 people were
living with HIV in the UK in 2012, but one in five of them did not know they were
carrying the virus. If those people were identified and treated, then a further
3,500 cases of HIV transmission could be prevented within five years.
PMID- 25116539
TI - Tired of carrying the burden of fatigue.
AB - A high proportion of people with rheumatoid arthritis experience fatigue. This
has a severe effect on their wellbeing, yet the symptom is rarely understood and
poorly managed by healthcare professionals. Nurses are being urged to recognise
the issues and explore effective treatment options with patients.
PMID- 25116540
TI - Learn to see patients in their own world.
AB - Insights from the social sciences can help nurses understand the influences that
shaped their patients and the decisions they make. This can develop empathy and
encourage better care. Nurses are passionate about their patients' wellbeing.
They can use the social sciences to improve the care they deliver and improve
their patients' lives.
PMID- 25116541
TI - Royal Naval nursing: 'testing but worth it'.
AB - Inga Kennedy is the most senior nurse in the Royal Navy. She enjoys the
commitment and discipline required by a career in the armed forces and says the
work offers great opportunities for nurses. Her career highlights have included
checking that injured personnel in Afghanistan were receiving the best care
possible.
PMID- 25116552
TI - First Aid for Cyclists app.
AB - This new, free app from St John Ambulance gives cyclists the skills to deal with
the most common cycling injuries.
PMID- 25116554
TI - RCN faces challenges over rising inequalities within profession.
AB - It is difficult to understand why the RCN will not join colleagues in the Royal
College of Midwives and other health unions in balloting members on industrial
action (Editorial and News July 30). Is the RCN fearful of the outcome should the
response be a yes?
PMID- 25116555
TI - It is time to take industrial action to reverse the sell-off of the NHS.
AB - As a nurse at St Thomas' Hospital in London during the strikes in the 1980s, I
never wanted to strike, having seen the effects on patient care (Letters May 21).
PMID- 25116556
TI - Unite calls on the NMC to reject the proposed 20% fee increase.
AB - We at Unite are opposed to the proposal from the Nursing and Midwifery Council
(NMC) to increase the registration fee from L100 a year to L120 in March next
year (News July 30 and August 6).
PMID- 25116557
TI - Remembering Herbert Sulzbach and those who work for peace.
AB - As we commemorate those who gave their lives in the first world war, it is
important that we also remember those who have worked to foster good relations
between former combatants.
PMID- 25116560
TI - Looking at people as individuals is vital to any work assessment.
AB - I agree with the recent Commons committee report recommending the scrapping,
because of design flaws, of the Employment and Support Allowance for people who
are unable to work because of disability or sickness (News July 30).
PMID- 25116561
TI - Force-feeding is in the interests of the state, not its prisoners.
AB - Further to Paul Hegarty's letter, 'Force-feeding is wrong and nurses should play
no part' (July 30), the International Council of Nurses is clear about the role
of nurses.
PMID- 25116562
TI - Service user and carer involvement in pre-registration student selection.
AB - An online questionnaire was undertaken to evaluate the involvement of service
users and carers in the student selection process and to identify how the pre
registration process might be enhanced. Respondents comprised 34 students, all of
whom had been selected for the pre-registration nursing education programme
following this process, and 22 others, including service users and carers,
practitioners, and lecturers, who had been involved in the selection process. A
positive attitude to the involvement of service users and carers was evident in
all groups, although there were some concerns and suggestions about how and when
involvement of service users and carers should occur. The main findings were that
service users could have an important role in contextualising mental health in
people's lives.
PMID- 25116563
TI - Using personal narrative to deepen emotional awareness of practice.
AB - Storytelling is intrinsic to human beings, and stories can explain events,
stances taken and actions engaged in. When experience is represented as story it
can become more organised and be used for analysis, critique and learning.
Experience is important in nursing, as it is in many other practice-based
professions, and it can contribute much to nurses' learning. Through a process of
sharing and engaging with the author's personal stories, this article encourages
nurses to begin to organise their own experiences in story form for use in
learning and as part of their personal and professional development.
PMID- 25116564
TI - Assessment and management of patients with ankle injuries.
AB - Foot and ankle injuries are common and can have a significant effect on an
individual's daily activities. Nurses have an important role in the assessment,
management, ongoing care and support of patients with ankle injuries. An
understanding of the anatomy and physiology of the ankle enables nurses to
identify significant injuries, which may result in serious complications, and
communicate effectively with the multidisciplinary team to improve patient care
and outcomes.
PMID- 25116565
TI - Acute confusion.
AB - Acute confusion, an acute cognitive impairment associated with severe illness, is
often termed delirium. Delirium seldom resolves steadily but goes through cycles
of improving and then worsening.
PMID- 25116568
TI - Bringing the clinic to the class.
AB - The transformation of nurse education from diploma to degree has been coupled
with greater emphasis on the use of evidence in practice. As a result, teaching
staff have been trying to improve the integration of theory and practice
learning.
PMID- 25116566
TI - Express yourself.
AB - Communication has always been a vital part of nursing. As students, we learned
about therapeutic communication and the differences between sympathy, empathy,
and rapport. I remember struggling with those differences and when to use each
most appropriately with patients, families, classmates and lecturers. Now, I
apply these principles at work with staff.
PMID- 25116569
TI - Sharps practice in focus.
AB - The EU Sharps Directive on the prevention of sharps injuries in the healthcare
sector (see resources ) was incorporated into the national law of all EU member
states on May 11 2013.
PMID- 25116570
TI - Student life - African learning experience.
AB - Archbishop Desmond Tutu once claimed that TB was the child of poverty, as well as
its parent and provider. My first insight into the truth of this came while I was
on a placement with Find & Treat, a pan-London tuberculosis (TB) service for
vulnerable communities.
PMID- 25116571
TI - Larval Population Density Alters Adult Sleep in Wild-Type Drosophila melanogaster
but Not in Amnesiac Mutant Flies.
AB - Sleep has many important biological functions, but how sleep is regulated remains
poorly understood. In humans, social isolation and other stressors early in life
can disrupt adult sleep. In fruit flies housed at different population densities
during early adulthood, social enrichment was shown to increase subsequent sleep,
but it is unknown if population density during early development can also
influence adult sleep. To answer this question, we maintained Drosophila larvae
at a range of population densities throughout larval development, kept them
isolated during early adulthood, and then tested their sleep patterns. Our
findings reveal that flies that had been isolated as larvae had more fragmented
sleep than those that had been raised at higher population densities. This effect
was more prominent in females than in males. Larval population density did not
affect sleep in female flies that were mutant for amnesiac, which has been shown
to be required for normal memory consolidation, adult sleep regulation, and brain
development. In contrast, larval population density effects on sleep persisted in
female flies lacking the olfactory receptor or83b, suggesting that olfactory
signals are not required for the effects of larval population density on adult
sleep. These findings show that population density during early development can
alter sleep behavior in adulthood, suggesting that genetic and/or structural
changes are induced by this developmental manipulation that persist through
metamorphosis.
PMID- 25116573
TI - The N-terminal transactivation domain of the glucocorticoid receptor mediates
apoptosis of human small cell lung cancer cells.
AB - Small cell lung cancer (SCLC) is an aggressive disease with a poor prognosis.
These cancers are deficient in glucocorticoid receptor (GR) expression, and
therefore, resistant to glucocorticoids. Overexpression of the GR both in vivo
and in vitro leads to apoptotic cell death suggesting that loss of GR is
favorable for cancer growth. Indeed, the GR promoter is silenced in SCLC cells by
methylation. We now show that treatment of the SCLC cell line (DMS79) cells with
the demethylating agent, 5-aza-2'-deoxycytidine (5-aza), results in significant
endogenous re-expression of both GRalpha and the ligand-independent GR-P. The GR
gene has a complex promoter region comprising nine alternative promoters, the
proximal seven of which lie within a CpG island. The endogenous re-expression
seen is attributed to the constitutive promoters 1B and 1C and 1J but
predominantly 1F, which we show to be heavily methylated in SCLC cells. Flow
cytometric analysis using the apoptotic marker, Annexin V, shows that this
endogenous re-expression is sufficient to drive the SCLC cells to apoptosis.
Apoptotic induction is specific to GR re-expression as cotreatment with 5-aza and
the GR antagonist, RU486 prevented apoptosis. Of the three functional GR domains
(the DNA binding domain, ligand binding domain, and transactivation domain), we
identified that the transactivation domain is essential for apoptosis in SCLC.
The discovery that endogenous re-expression of the GR in SCLC cells is sufficient
to induce apoptotic cell death by reversing a cancer-driven DNA methylation
effect may lead to the development of novel adjunct therapies.
PMID- 25116572
TI - Dissociating Cortical Activity during Processing of Native and Non-Native
Audiovisual Speech from Early to Late Infancy.
AB - Initially, infants are capable of discriminating phonetic contrasts across the
world's languages. Starting between seven and ten months of age, they gradually
lose this ability through a process of perceptual narrowing. Although
traditionally investigated with isolated speech sounds, such narrowing occurs in
a variety of perceptual domains (e.g., faces, visual speech). Thus far, tracking
the developmental trajectory of this tuning process has been focused primarily on
auditory speech alone, and generally using isolated sounds. But infants learn
from speech produced by people talking to them, meaning they learn from a complex
audiovisual signal. Here, we use near-infrared spectroscopy to measure blood
concentration changes in the bilateral temporal cortices of infants in three
different age groups: 3-to-6 months, 7-to-10 months, and 11-to-14-months.
Critically, all three groups of infants were tested with continuous audiovisual
speech in both their native and another, unfamiliar language. We found that at
each age range, infants showed different patterns of cortical activity in
response to the native and non-native stimuli. Infants in the youngest group
showed bilateral cortical activity that was greater overall in response to non
native relative to native speech; the oldest group showed left lateralized
activity in response to native relative to non-native speech. These results
highlight perceptual tuning as a dynamic process that happens across modalities
and at different levels of stimulus complexity.
PMID- 25116574
TI - Effects of a multidomain lifestyle modification on cognitive function in older
adults: an eighteen-month community-based cluster randomized controlled trial.
AB - BACKGROUND: A healthy lifestyle may protect against cognitive decline. We
examined outcomes in elderly individuals after 18 months of a five-group
intervention program consisting of various modalities to prevent cognitive
decline. METHODS: We conducted a cluster randomized controlled trial assessing
460 community-dwelling individuals aged 60 years and older in a geriatric
community mental health center in Suwon, Republic of Korea, between 2008 and
2010. We developed an intervention program based on the principles of contingency
management, which could be delivered by ordinary primary health workers. Group A
(n = 81) received standard care services. Group B (n = 80) received bimonthly
(once every 2 months) telephonic care management. Group C (n = 111) received
monthly telephonic care management and educational materials similar to those in
group B. Group D (n = 93) received bimonthly health worker-initiated visits and
counseling. Group E (n = 94) received bimonthly health worker-initiated visits,
counseling, and rewards for adherence to the program. RESULTS: The primary
outcome was the change in Mini-Mental State Examination (MMSE) scores from
baseline to the final follow-up visit at 18 months. Group E showed superior
cognitive function to group A (adjusted coefficient beta = 0.99, p = 0.044), with
participation in cognitive activities being the most important determining factor
among several health behaviors (adjusted coefficient beta = 1.04, p < 0.01).
CONCLUSIONS: Engaging in cognitive activities, in combination with positive
health behaviors, may be most beneficial in preserving cognitive abilities in
community-dwelling older adults.
PMID- 25116575
TI - The desmoid tumour: local control after surgical treatment.
AB - Desmoid tumours are uncommon non-malignant tumours that show a locally aggressive
growth pattern and a high local recurrence rate after surgery. Approximately 10%
of the desmoid tumours are associated with familial adenomatous polyposis (FAP).
Variable natural history of the disease challenges treatment decision-making in
the absence of prospective, randomised data. Association of this rare tumour to
GIST is speculated and the tumorigenesis may share common steps. This study
reviews given treatment and reports prognostic factors for local control and
concurrent neoplasms in patients evaluated by a single soft tissue tumour group.
Patients referred to the soft tissue tumour group at Helsinki University Central
Hospital (HUCH) for a desmoid tumour (primary or recurred) during 1987-2007 and
receiving surgical treatment with or without adjuvant treatment were included in
this retrospective review. All locations and also patients with a FAP-associated
tumour were included. Extra-abdominal location showed lower local control despite
the fact that 27% of patients also received radiation therapy. One amputation was
performed. Female sex and location in the rectus abdominis muscle predicted
improved local control in multivariate analysis. In this review, the occurrence
(14%) of concurrent neoplasms was higher than expected with unusual tumour types
noted including two GISTs. In those patients in whom surgical treatment is
chosen, adjuvant radiation therapy should also be considered in order to decrease
morbidity from aggressive surgery aiming at R0 resection. Further studies are
suggested to illuminate the biological association between the desmoid tumour and
other neoplasms.
PMID- 25116577
TI - Intracoronary injection of CD34-cells in chronic ischemic heart failure: 7 years
follow-up of the DanCell study.
AB - OBJECTIVES: Seven years ago, the DanCell study was carried out to test the
hypothesis of improvement in left ventricular ejection fraction (LVEF) following
repeated intracoronary injections of autologous bone marrow-derived stem cells
(BMSCs) in patients suffering from chronic ischemic heart failure. In this post
hoc analysis, the long-term effect of therapy is assessed. METHODS: 32 patients
[mean age 61 (SD +/- 9), 81% males] with systolic dysfunction (LVEF 33 +/- 9%)
received two repeated intracoronary infusions (4 months apart) of autologous
BMSCs (1,533 +/- 765 * 10(6) BMSCs including 23 +/- 11 * 10(6) CD34(+) cells and
14 +/- 7 * 10(6) CD133(+) cells). Patients were followed for 7 years and deaths
were recorded. RESULTS: During follow-up, 10 patients died (31%). In univariate
regression analysis, the total number of BMSCs, CD34(+) cell count and CD133(+)
cell count did not significantly correlate with survival (hazard ratio: 0.999,
95% CI: 0.998-1.000, p = 0.24; hazard ratio: 0.94, 95% CI: 0.88-1.01, p = 0.10,
and hazard ratio: 0.96, 95% CI: 0.87-1.07, p = 0.47, respectively). After
adjustment for baseline variables in multivariate regression analysis, the
CD34(+) cell count was significantly associated with survival (hazard ratio:
0.90, 95% CI: 0.82-1.00, p = 0.04). CONCLUSIONS: Intracoronary injections of a
high number of CD34(+) cells may have a beneficial effect on chronic ischemic
heart failure in terms of long-term survival.
PMID- 25116579
TI - The medicinal chemistry and drug development of novel antimalarials.
PMID- 25116578
TI - Antimalarial bicyclic peroxides belonging to the G-factor family: mechanistic
aspects of their formation and iron (II) induced reduction.
AB - Artemisinin and its derivatives are peroxide-containing compounds targeting P.
falciparum. We review here structural analogues of bicyclic peroxides belonging
to the G factors family presenting antimalarial properties. They were synthesised
under Mannich type conditions, followed by an autoxidation step resulting
exclusively in the peroxide. As the electron transfer from haem or free iron to
the peroxide is the first step in the mode of action of artemisinin-like
compounds, the redox properties of some endoperoxides were studied by
electrochemistry allowing the evaluation of the reduction standard potentials.
The Fe(II) induced reduction was also investigated and the reactivity of the C
centered radical intermediate formed was linked to the antimalarial activity.
These bicyclic peroxides both with various hybrid molecules containing the
endoperoxide framework were evaluated in vitro against Plasmodium falciparum.
They exhibited moderate to good activities.
PMID- 25116580
TI - 4-aminoquinoline based molecular hybrids as antimalarials: an overview.
AB - In recent times, the novel concept of generating hybrid molecules by
pharmacophoric hybridisation approach is fast becoming an alternative to other
existing strategies of drug development. These hybrids also known as 'dual drugs'
or 'double drugs' are especially found to be effective in overcoming drug
resistance problems. Towards this end, a lot of effort has been put for
generating 4-aminoquinoline based hybrid molecules as next generation
antimalarial drugs effective in malarial chemotherapy. This short review deals
about the recent advances carried in the field of 4-aminoquinoline based
molecular hybrids as potential antimalarial agents. It also presents a brief and
simplified story on the development of 4-aminoquinolines as a mainstay in
malarial research programmes.
PMID- 25116581
TI - Ferroquine as an oxidative shock antimalarial.
AB - Over the course of the development of the antimalarial ferroquine, we have
developed many ideas about its specific mechanism of action. Those ideas have
enabled us to propose several experiments to control the validity of these
hypotheses concerning differences between ferroquine and chloroquine and their
respective mechanisms of action. We have now established an ultimate theory
reconciling the hydrogen bond and the redox mechanisms hypotheses of ferroquine
and fitting a wider range of published experimental results.
PMID- 25116583
TI - Exploring prodrug approaches for albitiazolium and its analogues.
AB - Choline analogues such as bis-thiazolium salts are thought to inhibit choline
transport into Plasmodium-infected erythrocytes, thus preventing parasite PC
biosynthesis, and also to interact with plasmodial haemoglobin degradation in the
food vacuole. This new and multiple mode of action is a major asset of these new
class of antimalarials, as they could help delay resistance development. We
synthesized and designed various sets of analogues, notably prodrugs, since the
oral bioavailability of bis-thiazolium salts is relatively low. The chemistry
underlying this synthesis relies on inexpensive and readily available starting
materials and is straightforward. This is essential since the ultimate objective
is to obtain affordable and orally available drugs for uncomplicated malaria
treatment.
PMID- 25116584
TI - Antimalarial activities of indolones and derivatives.
AB - The search for antimalarial compounds continues to be an area of intensive
investigation in medicinal chemistry. This review presents the structural
variations around the indolone-N-oxide core. From these pharmacomodulation
studies, new antiplasmodial agents with various structures have emerged. Most of
the molecules generated from reduced forms of the indolone scaffold have led to
compounds with antiplasmodial properties. These results confirm the importance of
the redox reversibility of the bioreducible N=C bond in these series to obtain
antimalarial activities.
PMID- 25116582
TI - 4(1H)-pyridone and 4(1H)-quinolone derivatives as antimalarials with
erythrocytic, exoerythrocytic, and transmission blocking activities.
AB - Infectious diseases are the second leading cause of deaths in the world with
malaria being responsible for approximately the same amount of deaths as cancer
in 2012. Despite the success in malaria prevention and control measures
decreasing the disease mortality rate by 45% since 2000, the development of
single-dose therapeutics with radical cure potential is required to completely
eradicate this deadly condition. Targeting multiple stages of the malaria
parasite is becoming a primary requirement for new candidates in antimalarial
drug discovery and development. Recently, 4(1H)- pyridone, 4(1H)-quinolone,
1,2,3,4-tetrahydroacridone, and phenoxyethoxy-4(1H)-quinolone chemotypes have
been shown to be antimalarials with blood stage activity, liver stage activity,
and transmission blocking activity. Advancements in structure-activity
relationship and structure-property relationship studies, biological evaluation
in vitro and in vivo, as well as pharmacokinetics of the 4(1H)-pyridone and 4(1H)
quinolone chemotypes are discussed.
PMID- 25116585
TI - New anti-malarial drugs: who cares?
AB - Most of the people suffering malaria do not know how complex is that disease and
how hard searchers are working to fight against it. Some of these people are
dying from malaria while still efficient drug combinations should have save their
lives. But these drugs were not available for them when needed, or the diagnosis
was wrong, or the drugs were fake, or the doctor was untrained, or the patient
had no money. Should this terrible reality preclude the need for continuous
research to develop new antimalarial drugs? Should people working in laboratories
located in non-endemic countries adapt their project to that reality? Malaria
eradication, then elimination was announced and broadcasted in the late sixties,
and later forgotten. From that failure due to chloroquine resistance and after
decades of less arrogant work, billions of dollars are on the table again to
claim this goal. There were bed nets, drugs, vaccine and communication as
starters, let's hope people in endemic countries will be winners.
PMID- 25116586
TI - Quantum chemistry guide to PTRMS studies of as-yet undetected products of the
bromine-atom initiated oxidation of gaseous elemental mercury.
AB - A series of BrHgY compounds (Y = NO2, ClO, BrO, HOO, etc.) are expected to be
formed in the Br-initiated oxidation of Hg(0) to Hg(II) in the atmosphere. These
BrHgY compounds have not yet been reported in any experiment. This article
investigates the potential to use proton-transfer reaction mass spectrometry
(PTRMS) to detect these atmospherically important species. We show that reaction
of the standard PTRMS reagent (H3O(+)) with BrHgY leads to stable parent (M + 1)
ions, BrHgYH(+), for most of these radicals, Y. Rate constants for the proton
transfer reaction H3O(+) + BrHgY are computed using average dipole orientation
theory. Calculations are also carried out on the commercially available compounds
HgCl2, HgBr2, and HgI2 to enable tests of the present work.
PMID- 25116589
TI - Electronic control of the protonation rates of Fe-Fe bonds.
AB - Protonation at metal-metal bonds is of fundamental interest in the context of the
function of the active sites of hydrogenases and nitrogenases. In diiron
dithiolate complexes bearing carbonyl and electron-donating ligands, the metal
metal bond is the highest occupied molecular orbital (HOMO) with a "bent"
geometry. Here we show that the experimentally measured rates of protonation (kH)
of this bond and the energy of the HOMO as measured by the oxidation potential of
the complexes (E1/2(ox)) correlate in a linear free energy relationship: ln kH =
((F(c - betaE1/2(ox)))/(RT)), where c is a constant and beta is the dimensionless
Bronsted coefficient. The value of beta of 0.68 is indicative of a strong
dependence upon energy of the HOMO: measured rates of protonation vary over 6
orders of magnitude for a change in E1/2(ox) of ca. 0.55 V (ca. 11 orders of
magnitude/V). This relationship allows prediction of protonation rates of systems
that are either too fast to measure experimentally or that possess additional
protonation sites. It is further suggested that the nature of the bridgehead in
the dithiolate ligand can exert a stereoelectronic influence: bulky substituents
destabilize the HOMO, thereby increasing the rate of protonation.
PMID- 25116590
TI - Structural phase transitions of a layered organic-inorganic hybrid compound:
tetra(cyclopentylammonium) decachlorotricadmate(II), [C5H9NH3]4Cd3Cl10.
AB - A layered organic-inorganic hybrid compound, tetra(cyclopentylammonium)
decachlorotricadmate(II) (1), in which the two-dimensional [Cd3Cl10](4-)n
networks built up from three face-sharing CdCl6 octahedra are separated by
cyclopentylammonium cation bilayers, has been discovered as a new phase
transition material. It undergoes two successive structural phase transitions, at
197.3 and 321.6 K, which were confirmed by differential scanning calorimetry
measurements, variable-temperature structural analyses, and dielectric
measurements. The crystal structures of 1 determined at 93, 298, and 343 K are
solved in P212121, Pbca, and Cmca, respectively. A precise analysis of the
structural differences between these three structures reveals that the origin of
the phase transition at 197.3 K is ascribed to the order-disorder transition of
the cyclopentylammonium cations, while the phase transition at 321.6 K originates
from the distortion of the two-dimensional [Cd3Cl10](4-)n network.
PMID- 25116591
TI - Sharing the tracks to good tucker: identifying the benefits and challenges of
implementing community food programs for Aboriginal communities in Victoria.
AB - Food insecurity is a significant issue in the Victorian Aboriginal population,
contributing to the health disparity and reduced life expectancy. Community food
programs are a strategy used to minimise individual level food insecurity, with
little evidence regarding their effectiveness for Aboriginal populations. The aim
of this study was to explore the role of community food programs operating for
Aboriginal people in Victoria and their perceived influence on food access and
nutrition. Semistructured interviews were conducted with staff (n=23) from a
purposive sample of 18 community food programs across Victoria. Interviews
explored the programs' operation, key benefits to the community, challenges and
recommendations for setting up a successful community food program. Results were
analysed using a qualitative thematic approach and revealed three main themes
regarding key factors for the success of community food programs: (1) community
food programs for Aboriginal people should support access to safe, affordable,
nutritious food in a socially and culturally acceptable environment; (2) a
community development approach is essential for program sustainability; and (3)
there is a need to build the capacity of community food programs as part of a
strategy to ensure sustainability. Community food programs may be an effective
initiative for reducing food insecurity in the Victorian Aboriginal population.
PMID- 25116588
TI - Macrophage-specific NOX2 contributes to the development of lung emphysema through
modulation of SIRT1/MMP-9 pathways.
AB - Reactive oxygen species (ROS) participate in the pathogenesis of emphysema. Among
ROS-producing enzymes, NOX NADPH oxidases are thought to be responsible for
tissue injury associated with several lung pathologies. To determine whether NOX2
and/or NOX1 participate in the development of emphysema, their expression
patterns were first studied by immunohistochemistry in the lungs of emphysematous
patients. Subsequently, we investigated their contribution to elastase-induced
emphysema using NOX2- and NOX1-deficient mice. In human lung, NOX2 was mainly
detected in macrophages of control and emphysematous lungs, while NOX1 was
expressed in alveolar epithelium and bronchial cells. We observed an elevated
number of NOX2-positive cells in human emphysematous lungs, as well as increased
NOX2 and NOX1 mRNA expression in mouse lungs following elastase exposure.
Elastase-induced alveolar airspace enlargement and elastin degradation were
prevented in NOX2-deficient mice, but not in NOX1-deficient mice. This protection
was independent of inflammation and correlated with reduced ROS production.
Concomitantly, an elevation of sirtuin 1 (SIRT1) level and a decrease of matrix
metalloproteinase-9 (MMP-9) expression and activity were observed in alveolar
macrophages and neutrophils. We addressed the specific role of macrophage
restricted functional NOX2 in elastase-induced lung emphysema using Ncf1 mutant
mice and Ncf1 macrophage rescue mice (Ncf1 mutant mice with transgenic expression
of Ncf1 only in CD68-positive mononuclear phagocytes; the MN mouse). Compared to
WT mice, the lack of functional NOX2 led to decreased elastase-induced ROS
production and protected against emphysema. In contrast, ROS production was
restored specifically in macrophages from Ncf1 rescue mice and contributes to
emphysema. Taken together, our results demonstrate that NOX2 is involved in the
pathogenesis of human emphysema and macrophage-specific NOX2 participates in
elastase-induced emphysema through the involvement of SIRT1/MMP-9 pathways in
mice.
PMID- 25116593
TI - Imaging molecular adsorption and desorption dynamics on graphene using terahertz
emission spectroscopy.
AB - Being an atomically thin material, graphene is known to be extremely susceptible
to its environment, including defects and phonons in the substrate on which it is
placed as well as gas molecules that surround it. Thus, any device design using
graphene has to take into consideration all surrounding components, and device
performance needs to be evaluated in terms of environmental influence. However,
no methods have been established to date to readily measure the density and
distribution of external perturbations in a quantitative and non-destructive
manner. Here, we present a rapid and non-contact method for visualizing the
distribution of molecular adsorbates on graphene semi-quantitatively using
terahertz time-domain spectroscopy and imaging. We found that the waveform of
terahertz bursts emitted from graphene-coated InP sensitively changes with the
type of atmospheric gas, laser irradiation time, and ultraviolet light
illumination. The terahertz waveform change is explained through band structure
modifications in the InP surface depletion layer due to the presence of localized
electric dipoles induced by adsorbed oxygen. These results demonstrate that
terahertz emission serves as a local probe for monitoring adsorption and
desorption processes on graphene films and devices, suggesting a novel two
dimensional sensor for detecting local chemical reactions.
PMID- 25116594
TI - Optimization of ethyl ester production assisted by ultrasonic irradiation.
AB - This study presents the optimization of the continuous flow potassium hydroxide
catalyzed synthesis of ethyl ester from palm oil with ultrasonic assistance. The
process was optimized by application of factorial design and response surface
methodology. The independent variables considered were ethanol to oil molar
ratio, catalyst concentration, reaction temperature and ultrasonic amplitude; and
the response was ethyl ester yield. The results show that ethanol to oil molar
ratio, catalyst concentration, and ultrasonic amplitude have positive effect on
ethyl ester yield, whereas reaction temperature has negative influence on ethyl
ester yield. Second-order models were developed to predict the responses analyzed
as a function of these three variables, and the developed models predicts the
results in the experimental ranges studied adequately. This study shows that
ultrasonic irradiation improved the ethyl ester production process to achieve
ethyl ester yields above 92%.
PMID- 25116595
TI - Application of ultrasound for enhanced extraction of prebiotic oligosaccharides
from selected fruits and vegetables.
AB - Ultrasound assisted extraction (UAE) was used to extract oligosaccharides from
selected fruits (blueberry, nectarine, raspberry, watermelon) and vegetables
(garlic, Jerusalem artichoke, leek, scallion, spring garlic and white onion). The
individual fractions of the oligosaccharides were analyzed: 1-kestose (GF2),
nystose (GF3) and 1F-beta-fructofuranosylnystose (GF4) from the fructo
oligosaccharides (FOS), and raffinose and stachyose from the raffinose family
oligosaccharides (RFO). Extraction parameters including solvent concentration (35
85% v/v), extraction temperature (25-50 degrees C) and sonication time (5-15min)
were examined using response surface methodology (RSM). Ethanol concentration of
63% v/v, temperature of 40 degrees C and extraction time of 10min gave maximal
concentration of the extracted oligosaccharides. The experimental values under
optimal conditions were consistent with the predicted values. UAE increased the
concentration of extracted oligosaccharides in all fruits and vegetables from 2
to 4-fold compared to conventional extraction. The highest increase of total
oligosaccharides extracted by UAE was detected in Jerusalem artichoke, 7.17+/
0.348g/100gFW, compared to 1.62+/-0.094g/100gFW with conventional method.
PMID- 25116592
TI - Clustering nuclear receptors in liver regeneration identifies candidate
modulators of hepatocyte proliferation and hepatocarcinoma.
AB - BACKGROUND & AIMS: Liver regeneration (LR) is a valuable model for studying
mechanisms modulating hepatocyte proliferation. Nuclear receptors (NRs) are key
players in the control of cellular functions, being ideal modulators of hepatic
proliferation and carcinogenesis. METHODS & RESULTS: We used a previously
validated RT-qPCR platform to profile modifications in the expression of all 49
members of the NR superfamily in mouse liver during LR. Twenty-nine NR
transcripts were significantly modified in their expression during LR, including
fatty acid (peroxisome proliferator-activated receptors, PPARs) and oxysterol
(liver X receptors, Lxrs) sensors, circadian masters RevErbalpha and RevErbbeta,
glucocorticoid receptor (Gr) and constitutive androxane receptor (Car). In order
to detect the NRs that better characterize proliferative status vs. proliferating
liver, we used the novel Random Forest (RF) analysis to selected a trio of down
regulated NRs (thyroid receptor alpha, Tralpha; farsenoid X receptor beta,
Fxrbeta; Ppardelta) as best discriminators of the proliferating status. To
validate our approach, we further studied PPARdelta role in modulating hepatic
proliferation. We first confirmed the suppression of PPARdelta both in LR and
human hepatocellular carcinoma at protein level, and then demonstrated that
PPARdelta agonist GW501516 reduces the proliferative potential of hepatoma cells.
CONCLUSIONS: Our data suggest that NR transcriptome is modulated in proliferating
liver and is a source of biomarkers and bona fide pharmacological targets for the
management of liver disease affecting hepatocyte proliferation.
PMID- 25116596
TI - Combining collagen and bioactive glasses for bone tissue engineering: a review.
AB - Collagen (COL), the most abundant protein in mammals, offers a wide range of
attractive properties for biomedical applications which are the result of its
biocompatibility and high affinity to water. However, due to the relative low
mechanical properties of COL its applications are still limited. To tackle this
disadvantage of COL, especially in the field of bone tissue engineering, COL can
be combined with bioactive inorganic materials in a variety of composite systems.
One of such systems is the collagen-bioactive glass (COL-BG) composite family,
which is the theme of this Review. BG fillers can increase compressive strength
and stiffness of COL-based structures. This article reviews the relevant
literature published in the last 15 years discussing the fabrication of a variety
of COL-BG composites. In vitro cell studies have demonstrated the osteogenic,
odontogenic, and angiogenic potential of these composite systems, which has been
confirmed by stimulating specific biochemical indicators of relevant cells. Bony
integration and connective tissue vessel formation have also been studied by
implantation of the composites in vivo. Areas of future research in the field of
COL-BG systems, based on current challenges, and gaps in knowledge are
highlighted.
PMID- 25116597
TI - Effect of oxygen, moisture and illumination on the stability and reliability of
dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT) OTFTs during operation and
storage.
AB - We report a systemic study of the stability of organic thin film transistors
(OTFTs) both in storage and under operation. Apart from a thin polystyrene buffer
layer spin-coated onto the gate dielectric, the constituent parts of the OTFTs
were all prepared by vacuum evaporation. The OTFTs are based on the
semiconducting small molecule dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene
(DNTT) deposited onto the surface of a polystyrene-buffered in situ polymerized
diacrylate gate insulator. Over a period of 9 months, no degradation of the hole
mobility occurred in devices stored either in the dark in dry air or in
uncontrolled air and normal laboratory fluorescent lighting conditions. In the
latter case, rather than decreasing, the mobility actually increased almost 2
fold to 1.5 cm(2)/(V . s). The devices also showed good stability during repeat
on/off cycles in the dark in dry air. Exposure to oxygen and light during the
on/off cycles led to a positive shift of the transfer curves due to electron
trapping when the DNTT was biased into depletion by the application of positive
gate voltage. When operated in accumulation, negative gate voltage under the same
conditions, the transfer curves were stable. When voltage cycling in moist air in
the dark, the transfer curves shifted to negative voltages, thought to be due to
the generation of hole traps either in the semiconductor or its interface with
the dielectric layer. When subjected to gate bias stress in dry air in the dark
for at least 144 h, the device characteristics remained stable.
PMID- 25116598
TI - Small changes result in large differences: discovery of (-)-incrustoporin
derivatives as novel antiviral and antifungal agents.
AB - On the basis of the structure of natural product (-)-incrustoporin (1), a series
of lactone compounds 4a-i and 5a-i were designed and synthesized from
nitroolefin. The antiviral and antifungal activities of these compounds were
evaluated in vitro and in vivo. The small changes between 4 and 5 at the 3,4
position result in large differences in bioactivities. Compounds 4 exhibited
significantly higher antiviral activity against tobacco mosaic virus (TMV) than
dehydro compounds 5. However, the antifungal activity of 4 is relatively lower
than that of 5. Compounds 4a, 4c, and 4i with excellent in vivo anti-TMV activity
emerged as new antiviral lead compounds. Compounds 5d-g showed superiority over
the commercial fungicides chlorothalonil and carbendazim against Cercospora
arachidicola Hor at 50 mg kg(-1). The present study provides fundamental support
for the development and optimization of (-)-incrustoporin derivatives as
potential inhibitors of plant virus and pathogenic fungi.
PMID- 25116599
TI - Microfluidic device with integrated microfilter of conical-shaped holes for high
efficiency and high purity capture of circulating tumor cells.
AB - Capture of circulating tumor cells (CTCs) from peripheral blood of cancer
patients has major implications for metastatic detection and therapy analyses.
Here we demonstrated a microfluidic device for high efficiency and high purity
capture of CTCs. The key novelty of this approach lies on the integration of a
microfilter with conical-shaped holes and a micro-injector with cross-flow
components for size dependent capture of tumor cells without significant
retention of non-tumor cells. Under conditions of constant flow rate, tumor cells
spiked into phosphate buffered saline could be recovered and then cultured for
further analyses. When tumor cells were spiked in blood of healthy donors, they
could also be recovered at high efficiency and high clearance efficiency of white
blood cells. When the same device was used for clinical validation, CTCs could be
detected in blood samples of cancer patients but not in that of healthy donors.
Finally, the capture efficiency of tumor cells is cell-type dependent but the
hole size of the filter should be more closely correlated to the nuclei size of
the tumor cells. Together with the advantage of easy operation, low-cost and high
potential of integration, this approach offers unprecedented opportunities for
metastatic detection and cancer treatment monitoring.
PMID- 25116600
TI - Fatty acid desaturation index in human plasma: comparison of different analytical
methodologies for the evaluation of diet effects.
AB - Stearoyl-CoA desaturase 1 (SCD1) plays a role in the development of obesity and
related conditions, such as insulin resistance, and potentially also in
neurological and heart diseases. The activity of SCD1 can be monitored using the
desaturation index (DI), the ratio of product (16:1n-7 and 18:1n-9) to precursor
(16:0 and 18:0) fatty acids. Here, different analytical strategies were applied
to identify the method which best supports SCD1 biology. A novel effective
approach was the use of the SCD1-independent fatty acid (16:1n-10) as a negative
control. The first approach was based on a simple extraction followed by neutral
loss triglyceride fatty acid analysis. The second approach was based on the
saponification of triglycerides followed by fatty acid analysis (specific for the
position of the double bond within monounsaturated fatty acids (MUFAs)). In
addition to the analytical LC-MS assays, different matrices (plasma total
triglyceride fraction and the very low-density lipoprotein (VLDL) fraction) were
investigated to identify the best for studying changes in SCD1 activity. Samples
from volunteers on a high-carbohydrate diet were analyzed. Both ultra HPLC
(UHPLC)-MS-based assays showed acceptable accuracies (75-125% of nominal) and
precisions (<20%) for the analysis of DI-specific fatty acids in VLDL and plasma.
The most specific assay for the analysis of the liver SCD activity was then
validated for specificity and selectivity, intra- and interday accuracy and
precision, matrix effects, dilution effects, and analyte stability. After 3 days
of high-carbohydrate diet, only the specific fatty acids in human plasma VLDL
showed a significant increase in DI and associated SCD1 activity.
PMID- 25116601
TI - Size-exclusion chromatography-from high-performance to ultra-performance.
AB - Size-exclusion chromatography (SEC) enables measurement of the average molecular
weights and molecular-weight distributions of polymers. Because these
characteristics may, in turn, be correlated with important performance
characteristics of plastics, SEC is an essential analytical technique for
characterization of macromolecules. Although SEC is one of the oldest
instrumental chromatographic techniques, it is still under continuous
development, as a result of the great demand for increased resolution and faster
analysis in SEC. Ultra-high-pressure size-exclusion chromatography (UHPSEC) was
recently introduced to satisfy the growing demands of analytical chemists. Using
instrumentation capable of generating very high pressures and columns packed with
small particles, this technique enables greater separation efficiency and faster
analysis than are achieved with conventional SEC. UHPSEC is especially
advantageous for high-resolution analysis of oligomers, for very rapid polymer
separations, and as a second dimension in comprehensive two-dimensional liquid
chromatography of polymers. In this paper we discuss the benefits of UHPSEC for
separation of macromolecules, with examples from the literature.
PMID- 25116602
TI - Analysis of N-acylhomoserine lactone dynamics in continuous cultures of
Pseudomonas putida IsoF by use of ELISA and UHPLC/qTOF-MS-derived measurements
and mathematical models.
AB - In this interdisciplinary approach, the dynamics of production and degradation of
the quorum sensing signal 3-oxo-decanoylhomoserine lactone were studied for
continuous cultures of Pseudomonas putida IsoF. The signal concentrations were
quantified over time by use of monoclonal antibodies and ELISA. The results were
verified by use of ultra-high-performance liquid chromatography. By use of a
mathematical model we derived quantitative values for non-induced and induced
signal production rate per cell. It is worthy of note that we found rather
constant values for different rates of dilution in the chemostat, and the values
seemed close to those reported for batch cultures. Thus, the quorum-sensing
system in P. putida IsoF is remarkably stable under different environmental
conditions. In all chemostat experiments, the signal concentration decreased
strongly after a peak, because emerging lactonase activity led to a lower
concentration under steady-state conditions. This lactonase activity probably is
quorum sensing-regulated. The potential ecological implication of such unique
regulation is discussed.
PMID- 25116603
TI - Separation and quantification of monoclonal-antibody aggregates by hollow-fiber
flow field-flow fractionation.
AB - Hollow-fiber-flow field-flow fractionation (HF5) separates protein molecules on
the basis of the difference in the diffusion coefficient, and can evaluate the
aggregation ratio of proteins. However, HF5 is still a minor technique because
information on the separation conditions is limited. We examined in detail the
effect of different settings, including the main-flow rate, the cross-flow rate,
the focus point, the injection amount, and the ionic strength of the mobile
phase, on fractographic characteristics. On the basis of the results, we proposed
optimized conditions of the HF5 method for quantification of monoclonal antibody
in sample solutions. The HF5 method was qualified regarding the precision,
accuracy, linearity of the main peak, and quantitation limit. In addition, the
HF5 method was applied to non-heated Mab A and heat-induced-antibody-aggregate
containing samples to evaluate the aggregation ratio and the distribution extent.
The separation performance was comparable with or better than that of
conventional methods including analytical ultracentrifugation-sedimentation
velocity and asymmetric-flow field-flow fractionation.
PMID- 25116604
TI - Characterization of poly(2-vinylpyridine)-block-poly(methyl methacrylate)
copolymers and blends of their homopolymers by liquid chromatography at critical
conditions.
AB - Poly(2-vinylpyridine)s (P2VPs) are important polymers with extensive applications
in modern day material science. P2VP is an exceptional case for liquid
chromatography because of certain polar interactions with most of the stationary
phases. In the present study, we established the critical adsorption point (CAP)
of P2VP for the first time. The effectiveness of the method is demonstrated by
analyses of blends and block copolymers of P2VP and PMMA. The CAP of PMMA is
established for determination of molar mass of P2VP component of above mentioned
blends and block copolymers. The methods successfully demonstrate the separation
of both types of homopolymers from the rest of the samples in conjunction with
the determination of molar mass distribution of noncritical block or component.
PMID- 25116606
TI - Emulsion-templated silica nanocapsules formed using bio-inspired silicification.
AB - A novel, bio-inspired templating platform technology is reported for the
synthesis of biocompatible oil-core silica-shell nanocapsules with tunable shell
thickness by utilizing a designed bifunctional peptide. Furthermore, facile
encapsulation of an active molecule and its sustained release are demonstrated.
PMID- 25116607
TI - Remembering Obaid - one year later.
PMID- 25116605
TI - Effects of initial boost with TGF-beta 1 and grade of intervertebral disc
degeneration on 3D culture of human annulus fibrosus cells.
AB - BACKGROUND: Three-dimensional (3D) culture in porous biomaterials as well as
stimulation with growth factors are known to be supportive for intervertebral
disc cell differentiation and tissue formation. Unless sophisticated releasing
systems are used, however, effective concentrations of growth factors are
maintained only for a very limited amount of time in in vivo applications.
Therefore, we investigated, if an initial boost with transforming growth factor
beta 1 (TGF-beta 1) is capable to induce a lasting effect of superior
cartilaginous differentiation in slightly and severely degenerated human annulus
fibrosus (AF) cells. METHODS: Human AF tissue was harvested during surgical
treatment of six adult patients with lumbar spinal diseases. Grading of disc
degeneration was performed with magnet resonance imaging. AF cells were isolated
and expanded in monolayer culture and rearranged three-dimensionally in a porous
biomaterial consisting of stepwise absorbable poly-glycolic acid and poly-(lactic
co-glycolic) acid and a supportive fine net of non-absorbable polyvinylidene
fluoride. An initial boost of TGF-beta 1 or TGF-beta 1 and hyaluronan was applied
and compared with controls. Matrix formation was assessed at days 7 and 21 by (1)
histological staining of the typical extracellular matrix molecules proteoglycan
and type I and type II collagens and by (2) real-time gene expression analysis of
aggrecan, decorin, biglycan, type I, II, III, and X collagens as well as of
catabolic matrix metalloproteinases MMP-2 and MMP-13. RESULTS: An initial boost
with TGF-beta 1 or TGF-beta 1 and hyaluronan did not enhance the expression of
characteristic AF matrix molecules in our 3D culture system. AF cells showed high
viability in the progressively degrading biomaterial. Stratification by grade of
intervertebral disc degeneration showed that AF cells from both, slightly
degenerated, or severely degenerated tissue are capable of significant up
regulations of characteristic matrix molecules in 3D culture. AF cells from
severely degenerated tissue, however, displayed significantly lower up
regulations in some matrix molecules such as aggrecan. CONCLUSIONS: We failed to
show a supportive effect of an initial boost with TGF-beta 1 in our 3D culture
system. This underlines the need for further investigations on growth factor
releasing systems.
PMID- 25116608
TI - Recalling Obaid.
PMID- 25116609
TI - Remembering Obaid Siddiqi, a pioneer in the study of temperature-sensitive
paralytic mutants in Drosophila.
AB - Although Obaid Siddiqi's major research focus in neurogenetics was on
chemosensation and olfaction in Drosophila, he made seminal contributions to the
study of temperature-sensitive paralytic mutants that paved the way for research
that we and many other investigators have continued to pursue. Here we recount
Siddiqi's investigation and the impact it had on our own studies especially at a
formative stage of our careers. We acknowledge our debt to Obaid Siddiqi and
remember him fondly as an inspired and inspiring scientist, mentor, role model
and human being.
PMID- 25116610
TI - Molecular determinants of odorant receptor function in insects.
AB - The olfactory system of Drosophila melanogaster provides a powerful model to
study molecular and cellular mechanisms underlying function of a sensory system.
In the 1970s Siddiqi and colleagues pioneered the application of genetics to
olfactory research and isolated several mutant Drosophila with odorant-specific
defects in olfactory behaviour, suggesting that odorants are detected
differentially by the olfactory system. Since then basic principles of olfactory
system function and development have emerged using Drosophila as a model. Nearly
four decades later we can add computational methods to further our understanding
of how specific odorants are detected by receptors. Using a comparative approach
we identify two categories of short amino acid sequence motifs: ones that are
conserved family-wide predominantly in the C-terminal half of most receptors, and
ones that are present in receptors that detect a specific odorant, 4
methylphenol, found predominantly in the N-terminal half. The odorant-specific
sequence motifs are predictors of phenol detection in Anopheles gambiae and other
insects, suggesting they are likely to participate in odorant binding.
Conversely, the family-wide motifs are expected to participate in shared
functions across all receptors and a mutation in the most conserved motif leads
to a reduction in odor response. These findings lay a foundation for
investigating functional domains within odorant receptors that can lead to a
molecular understanding of odor detection.
PMID- 25116611
TI - A map of taste neuron projections in the Drosophila CNS.
AB - We provide a map of the projections of taste neurons in the CNS of Drosophila.
Using a collection of 67 GAL4 drivers representing the entire repertoire of Gr
taste receptors, we systematically map the projections of neurons expressing
these drivers in the thoracico-abdominal ganglion and the suboesophageal ganglion
(SOG). We define 9 categories of projections in the thoracico-abdominal ganglia
and 10 categories in the SOG. The projection patterns are modular, and can be
interpreted as combinations of discrete pattern elements. The elements can be
interpreted in terms of the taste organ from which the projections originate, the
structures from which they originate, and the quality of taste information that
they represent. The extensive diversity in projection patterns provides an
anatomical basis for functional diversity in responses elicited by different
taste stimuli.
PMID- 25116612
TI - Serotonergic neurons of the Drosophila air-puff-stimulated flight circuit.
AB - Monoaminergic modulation of insect flight is well documented. Recently, we
demonstrated that synaptic activity is required in serotonergic neurons for
Drosophila flight. This requirement is during early pupal development, when the
flight circuit is formed, as well as in adults. Using a Ca2+-activity-based GFP
reporter, here we show that serotonergic neurons in both prothoracic and
mesothoracic segments are activated upon air-puff-stimulated flight. Moreover
ectopic activation of the entire serotonergic system by TrpA1, a heat activated
cation channel, induces flight, even in the absence of an air-puff stimulus.
PMID- 25116613
TI - Ultradian rhythm unmasked in the Pdf clock mutant of Drosophila.
AB - A diverse range of organisms shows physiological and behavioural rhythms with
various periods. Extensive studies have been performed to elucidate the molecular
mechanisms of circadian rhythms with an approximately 24 h period in both
Drosophila and mammals, while less attention has been paid to ultradian rhythms
with shorter periods. We used a video-tracking method to monitor the movement of
single flies, and clear ultradian rhythms were detected in the locomotor
behaviour of wild type and clock mutant flies kept under constant dark
conditions. In particular, the Pigment-dispersing factor mutant (Pdf 01)
demonstrated a precise and robust ultradian rhythmicity, which was not
temperature compensated. Our results suggest that Drosophila has an endogenous
ultradian oscillator that is masked by circadian rhythmic behaviours.
PMID- 25116614
TI - Insights into brain development and disease from neurogenetic analyses in
Drosophila melanogaster.
AB - Groundbreaking work by Obaid Siddiqi has contributed to the powerful genetic
toolkit that is now available for studying the nervous system of Drosophila.
Studies carried out in this powerful neurogenetic model system during the last
decade now provide insight into the molecular mechanisms that operate in neural
stem cells during normal brain development and during abnormal brain
tumorigenesis. These studies also provide strong support for the notion that
conserved molecular genetic programs act in brain development and disease in
insects and mammals including humans.
PMID- 25116615
TI - Continuous evolution of laboratory strains of bacteria and yeast.
PMID- 25116616
TI - Gender based disruptive selection maintains body size polymorphism in Drosophila
melanogaster.
AB - Darwinian fitness in holometabolous insects like the fruit fly Drosophila
melanogaster is reported to be positively correlated with body size. If large
individuals in a population have higher fitness, then one would expect
directional selection to operate leading to uniformly large individuals. However,
size polymorphism persists in nature and needs further probing. We assessed the
effect of body size on some of the fitness and fitness-related traits in
replicate populations of genotypically large, genotypically small and
phenotypically small D. melanogaster flies. In this study, the time taken to
attain reproductive maturity and copulation duration were independent of fly
size. Fecundity and longevity of large females were significantly higher when
they partnered genotypically small males than when they were with genotypically
larger or phenotypically small males. The increased female longevity when in
association with genotypically small males was not due to selective early death
of males that would release the female partner from presumed cost of persistent
courtship. On the contrary, the genotypically as well as phenotypically small
males had significantly higher longevity than large males. The virility of the
genotypically small males was not significantly different from that of
genotypically large males. Our results clearly show that selection on body size
operates in the opposite direction (disruptive selection) for the two genders,
thus explaining the persistence of size polymorphisms in the holometabolous
insect, Drosophila melanogaster.
PMID- 25116617
TI - 2'-O-methyl nucleotide modified DNA substrates influence the cleavage
efficiencies of BamHI and BglII.
AB - Induction of endonucleolytic DNA cleavage is an essential event that links the
initiating stimuli to the final effects of cells. The cleavage efficiency and
thus the final yield could be affected by many factors, including structures of
DNA substrates, composite structures of enzymes-substrates or enzymes-nucleic
analogs and so on. However, it is not clear whether a nucleotide derivative
substituted in DNA substrates can influence the efficiency of enzymatic cleavage.
To investigate the effect of sugar pucker conformation on DNA-protein
interactions, we used 2'-O-methyl modified nucleotides (OMeN) to modify DNA
substrates of isocaudemers BamHI and BglII in this study, and used FRET assay as
an efficient method for analysis of enzyme cleavage. Experimental results
demonstrated that OMeN-substituted recognition sequences influenced the cleavage
rates significantly in a position-dependent manner. OMeN substitutions can reduce
the cleavage as expected. Surprisingly, OMeN substitutions can also enhance the
cleavage rates. The kinetics parameters of Vmax and Km have been obtained by
fitting the Michaelis-Menten kinetic equation. These 2'- OMe nucleotides could
behave as a regulatory element to modulate the enzymatic activity in vitro, and
this property could enrich our understanding about the endonuclease cleavage
mechanism and enhance our ability to regulate the enzymatic cleavage efficiency
for applications in synthetic biology.
PMID- 25116619
TI - Limnology and cyanobacterial diversity of high altitude lakes of Lahaul-Spiti in
Himachal Pradesh, India.
AB - Limnological data of four high altitude lakes from the cold desert region of
Himachal Pradesh, India, has been correlated with cyanobacterial diversity.
Physico-chemical characteristics and nutrient contents of the studied lakes
revealed that Sissu Lake is mesotrophic while Chandra Tal, Suraj Tal and Deepak
Tal are ultra-oligotrophic. Based on morphology and 16S rRNA gene sequence, a
total of 20 cyanobacterial species belonging to 11 genera were identified.
Canonical correspondence analysis distinguished three groups of species with
respect to their occurrence and nutrient/physical environment demand. The first
group, which included Nostoc linckia, N. punctiforme, Nodularia sphaerocarpa,
Geitlerinema acutissimum, Limnothrix redekii, Planktothrix agardhii and Plank.
clathrata, was characteristic of water with high nutrient content and high
temperature. The second group, including Gloeocapsopsis pleurocapsoides,
Leptolyngbya antarctica, L. frigida, Pseudanabaena frigida and N. spongiaeforme,
occurred in oligotrophic water with high pH and low temperature. The distribution
of third group of Cyanobium parvum, Synechocystis pevalekii, L. benthonica, L.
foveolarum, L. lurida, L. valderiana, Phormidium autumnale and P. chalybeum could
not be associated with a particular environmental condition because of their
presence in all sampling sites.
PMID- 25116618
TI - Avoiding acidic region streaking in two-dimensional gel electrophoresis: case
study with two bacterial whole cell protein extracts.
AB - Acidic region streaking (ARS) is one of the lacunae in two-dimensional gel
electrophoresis (2DE) of bacterial proteome. This streaking is primarily caused
by nucleic acid (NuA) contamination and poses major problem in the downstream
processes like image analysis and protein identification. Although cleanup and
nuclease digestion are practiced as remedial options, these strategies may incur
loss in protein recovery and perform incomplete removal of NuA. As a result, ARS
has remained a common observation across publications, including the recent ones.
In this work, we demonstrate how ultrasound wave can be used to shear NuA in
plain ice-cooled water, facilitating the elimination of ARS in the 2DE gels
without the need for any additional sample cleanup tasks. In combination with a
suitable buffer recipe, IEF program and frequent paper-wick changing approach, we
are able to reproducibly demonstrate the production of clean 2DE gels with
improved protein recovery and negligible or no ARS. We illustrate our procedure
using whole cell protein extracts from two diverse organisms, Escherichia coli
and Mycobacterium smegmatis. Our designed protocols are straightforward and
expected to provide good 2DE gels without ARS, with comparable times and
significantly lower cost.
PMID- 25116620
TI - Conserved C-terminal nascent peptide binding domain of HYPK facilitates its
chaperone-like activity.
AB - Human HYPK (Huntingtin Yeast-two-hybrid Protein K) is an intrinsically
unstructured chaperone-like protein with no sequence homology to known
chaperones. HYPK is also known to be a part of ribosome-associated protein
complex and present in polysomes. The objective of the present study was to
investigate the evolutionary influence on HYPK primary structure and its impact
on the protein's function. Amino acid sequence analysis revealed 105 orthologs of
human HYPK from plants, lower invertebrates to mammals. C-terminal part of HYPK
was found to be particularly conserved and to contain nascent polypeptide
associated alpha subunit (NPAA) domain. This region experiences highest selection
pressure, signifying its importance in the structural and functional evolution.
NPAA domain of human HYPK has unique amino acid composition preferring glutamic
acid and happens to be more stable from a conformational point of view having
higher content of a-helices than the rest. Cell biology studies indicate that
overexpressed C-terminal human HYPK can interact with nascent proteins, co
localizes with huntingtin, increases cell viability and decreases caspase
activities in Huntington's disease (HD) cell culture model. This domain is found
to be required for the chaperone-like activity of HYPK in vivo. Our study
suggested that by virtue of its flexibility and nascent peptide binding activity,
HYPK may play an important role in assisting protein (re)folding.
PMID- 25116621
TI - Skin anti-photoaging properties of ginsenoside Rh2 epimers in UV-B-irradiated
human keratinocyte cells.
AB - Ginseng, one of the most widely used herbal medicines, has a wide range of
therapeutic and pharmacological applications. Ginsenosides are the major
bioactive ingredients of ginseng, which are responsible for various
pharmacological activities of ginseng. Ginsenoside Rh2, known as an antitumour
ginsenoside, exists as two different stereoisomeric forms, 20(S)-ginsenoside Rh2
[20(S)-Rh2] and 20(R)-ginsenoside Rh2 [20(R)-Rh2]. This work aimed to assess and
compare skin anti-photoaging activities of 20(S)-Rh2 and 20(R)-Rh2 in UV-B
irradiated HaCat cells. 20(S)-Rh2, but not 20(R)-Rh2, was able to suppress UV-B
induced ROS production in HaCat cells. Both stereoisomeric forms could not
modulate cellular survival and NO level in UV-B-irradiated HaCat cells. Both
20(S)-Rh2 and 20(R)-Rh2 exhibited suppressive effects on UV-B-induced MMP-2
activity and expression in HaCat cells. In brief, the two stereoisomers of
ginsenoside Rh2, 20(S)-Rh2 and 20(R)-Rh2, possess skin anti-photoaging effects
but possibly in different fashions.
PMID- 25116622
TI - Herpes simplex virus types 1 and 2 modulate autophagy in SIRC corneal cells.
AB - Autophagy and apoptosis function as important early cellular defense mechanisms
in infections and other diseases. The outcome of an infection is determined by a
complex interplay between the pathogenic microorganism and these intracellular
pathways. To better understand the cytopathogenicity of Herpes simplex virus
types 1 and 2 (HSV-1 and - 2), we studied the effect of these viruses on the
autophagic and apoptotic processes in the SIRC corneal cell line. Infection with
the KOS strain of HSV-1 and a wild-type strain of HSV-2 enhanced autophagosome
formation, triggered cytoplasmic acidification, increased LC3B lipidation and
elevated the ratio of apoptotic cells. The autophagy inhibitor bafilomycin A1
triggered a significant increase in the apoptotic responses of HSV-1 and HSV-2
infected cells. Thus, both HSV types affect autophagy and apoptosis in a
coordinated fashion, and autophagy plays cytoprotective role in HSV-infected
cells via antagonizing apoptosis. Together these data implicate autophagy in the
pathogenic mechanism of herpetic keratitis.
PMID- 25116623
TI - Platelet-derived growth factor mediates interleukin-13-induced collagen I
production in mouse airway fibroblasts.
AB - Interleukin-13 (IL-13) is associated with the production of collagen in airway
remodelling of asthma. Yet, the molecular mechanisms underlying IL-13 induction
of collagen remain unclear; the aim of this study is to address this issue. IL-13
dose- and time-dependently-induced collagen I production in primary cultured
airway fibroblasts; this was accompanied with the STAT6 phosphorylation, and pre
treatment of cells with JAK inhibitor suppressed IL-13- induced collagen I
production. Further study indicated that IL-13 stimulated JAK/STAT6-dependent
PDGF production and subsequent ERK1/2 MAPK activation in airway fibroblasts, and
the presence of either PDGF receptor blocker or MEK inhibitor partially
suppressed IL-13-induced collagen I production. Taken together, our study
suggests that activation of JAK/STAT6 signal pathway and subsequent PDGF
generation and resultant ERK1/2 MAPK activation mediated IL-13-induced collagen I
production in airway fibroblasts.
PMID- 25116624
TI - Determining sensitive stages for learning to detect predators in larval bronzed
frogs: importance of alarm cues in learning.
AB - Successful survival and reproduction of prey organisms depend on their ability to
detect their potential predators accurately and respond effectively with suitable
defences. Predator detection can be innate or can be acquired through learning.We
studied prey-predator interactions in the larval bronzed frogs (Sylvirana
temporalis), which have the innate ability to detect certain predators. We
conducted a series of experiments to determine if the larval S. temporalis rely
solely on innate predator detection mechanisms or can also learn to use more
specific cues such as conspecific alarm cues for the purpose. The results of our
study clearly indicate that larval S. temporalis use both innate and learned
mechanisms for predator detection. Predator-naive tadpoles could detect
kairomones alone as a potential threat and responded by reducing activity,
suggesting an innate predator detection mechanism. Surprisingly, predator-naive
tadpoles failed to detect conspecific alarm cues as a potential threat, but
learned to do so through experience. After acquiring the ability to detect
conspecific alarm cues, they could associate novel predator cues with conspecific
alarm cues. Further, post feeding stages of larval S. temporalis are sensitive
for learning to detect conspecific alarm cues to label novel predators.
PMID- 25116625
TI - DNA barcoding of a new record of epi-endophytic green algae Ulvella leptochaete
(Ulvellaceae, Chlorophyta) in India.
AB - Epi-endophytic green algae comprise one of the most diverse and phylogenetically
primitive groups of green algae and are considered to be ubiquitous in the
world's oceans; however, no reports of these algae exist from India. Here we
report the serendipitous discovery of Ulvella growing on intertidal green algae
Cladophora glomerata and benthic red algae Laurencia obtusa collected from India.
DNA barcodes at nuclear ribosomal DNA Internal Transcriber Spacer (nrDNA ITS) 1
and 2 regions for Indian isolates from the west and east coasts have been
generated for the first time. Based on morphology and DNA barcoding, isolates
were identified as Ulvella leptochaete. Phylogenetic reconstruction of
concatenated dataset using Maximum Likelihood method differentiated Indian
isolates from other accessions of this alga available in Genbank, albeit with low
bootstrap support. Monophyly of Ulvella leptochaete was obvious in both of our
phylogenetic analyses. With this first report of epi-endophytic algae from Indian
territorial waters, the dire need to catalogue its cryptic diversity is
highlighted and avenues of future research are discussed.
PMID- 25116626
TI - Lantana camara L. (Verbenaceae) invasion along streams in a heterogeneous
landscape.
AB - Streams are periodically disturbed due to flooding, act as edges between habitats
and also facilitate the dispersal of propagules, thus being potentially more
vulnerable to invasions than adjoining regions. We used a landscape-wide transect
based sampling strategy and a mixed effects modelling approach to understand the
effects of distance from stream, a rainfall gradient, light availability and fire
history on the distribution of the invasive shrub Lantana camara L.(lantana) in
the tropical dry forests of Mudumalai in southern India. The area occupied by
lantana thickets and lantana stem abundance were both found to be highest closest
to streams across this landscape with a rainfall gradient. There was no advantage
in terms of increased abundance or area occupied by lantana when it grew closer
to streams in drier areas as compared to moister areas. On an average, the area
covered by lantana increased with increasing annual rainfall. Areas that
experienced greater number of fires during 1989-2010 had lower lantana stem
abundance irrespective of distance from streams. In this landscape, total light
availability did not affect lantana abundance. Understanding the spatially
variable environmental factors in a heterogeneous landscape influencing the
distribution of lantana would aid in making informed management decisions at this
scale.
PMID- 25116628
TI - Which dimensions of disability does the HIV Disability Questionnaire (HDQ)
measure? A factor analysis.
AB - PURPOSE: To assess the dimensions of disability measured by the HIV Disability
Questionnaire (HDQ), a newly developed 72-item self-administered questionnaire
that describes the presence, severity and episodic nature of disability
experienced by people living with HIV. METHODS: We recruited adults living with
HIV from hospital clinics, AIDS service organizations and a specialty hospital
and administered the HDQ followed by a demographic questionnaire. We conducted an
exploratory factor analysis using disability severity scores to determine the
domains of disability in the HDQ. We used the following steps: (a) ensured
correlations between items were >0.30 and <0.80; (b) conducted a principal
components analysis to extract factors; (c) used the Scree Test and eigenvalue
threshold >1.5 to determine the number of factors to retain; and d) used oblique
rotation to simplify the factor loading matrix. We assigned items to factors
based on factor loadings of >0.30. RESULTS: Of the 361 participants, 80% were men
and 77% reported living with at least two concurrent health conditions in
addition to HIV. The exploratory factor analysis suggested retaining six factors.
Items related to symptoms and impairments loaded on three factors (physical [20
items], cognitive [3 items], and mental and emotional health [11 items]) and
items related to worrying about the future, daily activities, and personal
relationships loaded on three additional factors (uncertainty [14 items],
difficulties with day-to-day activities [9 items], social inclusion [12 items]).
CONCLUSIONS: The HDQ has six domains: physical symptoms and impairments;
cognitive symptoms and impairments; mental and emotional health symptoms and
impairments; uncertainty; difficulties with day-to-day activities and challenges
to social inclusion. These domains establish the scoring structure for the
dimensions of disability measured by the HDQ. Implications for Rehabilitation As
individuals live longer and age with HIV, they may be living with the health
related consequences of HIV and concurrent health conditions, a concept that may
be termed disability. Measuring disability is important to understand the impact
of HIV and its comorbidities. The HIV Disability Questionnaire (HDQ) is a self
administered questionnaire developed to describe the presence, severity and
episodic nature of disability experienced by people living with HIV. The HDQ is
comprised of six domains of disability including: physical symptoms and
impairments (20 items); cognitive symptoms and impairments (3 items); mental and
emotional health symptoms and impairments (11 items); uncertainty (14 items);
difficulties with day-to-day activities (9 items) and challenges to social
inclusion (12 items). These domains represent the dimensions of disability
measured by the HDQ. The HDQ is the first known HIV-specific disability measure
for adults living with HIV. The HDQ may be used by clinicians and researchers to
assess disability experienced by adults living with HIV.
PMID- 25116629
TI - Stabilizing characteristics of rotator cuff muscles: a systematic review.
AB - PURPOSE: To systematically review the evidence in support of the purported
function of the rotator cuff muscles as dynamic stabilizers of the glenohumeral
joint. METHODS: Electronic searches were conducted using AMED, CINAHL, Medline
and SPORT Discus. Studies were required to include at least one characteristic of
a stabilizer muscle. Quality analysis was completed by two assessors
independently. Data were extracted for four main characteristics of stabilizer
muscles: (1) moment arm length, (2) onset of muscle activity, (3) joint stiffness
as measured by contribution of muscle activity to prevent joint translation, (4)
co-contraction as demonstrated by electromyography muscle activity and co
activation ratio. RESULTS: Twenty of the 1726 identified studies were selected
for the review. Rotator cuff muscles can limit joint translation (five studies)
and contribute to joint stiffness (one study), possess shorter moment arms in
some movements (three studies), but show limited evidence for stabilizing
characteristics of early onset (seven studies) and co-contraction (seven
studies). CONCLUSION: The rotator cuff muscles exhibited some stabilization
characteristics but not all. On the basis of our current low to moderate quality
evidence, the most likely, but as yet unverified, stabilization role for the
rotator cuff muscles appears to be limiting of translation in a direction
specific manner. IMPLICATIONS FOR REHABILITATION: Diagnostic tests currently used
are based largely on the assumption that the muscles of the rotator cuff can be
individually recruited as prime movers. Our findings demonstrate the need for
more research into the proposed stabilizing mechanisms of the rotator cuff
muscles to increase diagnostic accuracy and more targeted shoulder rehabilitation
programs. It may be that the rotator cuff muscles have a role in limiting
glenohumeral joint translation which is not reflected in the current diagnostic
tests and rehabilitation protocols. Further research is required to establish
this stabilizing characteristic in living subjects. Knowledge of the contribution
of rotator cuff muscle activation in limiting joint translation may be an
important aspect in properly assessing and quantifying the proposed function of
the rotator cuff muscles as dynamic stabilizers of the shoulder joint.
PMID- 25116627
TI - Does malaria epidemiology project Cameroon as 'Africa in miniature'?
AB - Cameroon, a west-central African country with a ~ 20 million population, is
commonly regarded as 'Africa in miniature' due to the extensive biological and
cultural diversities of whole Africa being present in a single-country setting.
This country is inhabited by ancestral human lineages in unique eco-climatic
conditions and diverse topography. Over 90 percent Cameroonians are at risk of
malaria infection, and ~ 41 percent have at least one episode of malaria each
year. Historically, the rate of malaria infection in Cameroon has fluctuated over
the years; the number of cases was about 2 million in 2010 and 2011. The
Cameroonian malaria control programme faces an uphill task due to high prevalence
of multidrug-resistant parasites and insecticide-resistant malaria vectors. Above
all, continued human migration from the rural to urban areas as well as
population exchange with adjoining countries, high rate of ecological
instabilities caused by deforestation, poor housing, lack of proper sanitation
and drainage system might have resulted in the recent increase in incidences of
malaria and other vector-borne diseases in Cameroon. The available data on eco
environmental variability and intricate malaria epidemiology in Cameroon reflect
the situation in the whole of Africa, and warrant the need for in-depth study by
using modern surveillance tools for meaningful basic understanding of the malaria
triangle (host-parasite-vector-environment).
PMID- 25116632
TI - Design, synthesis and aphicidal activity of N-terminal modified insect kinin
analogs.
AB - The insect kinins are a class of multifunctional insect neuropeptides present in
a diverse variety of insects. Insect kinin analogs showed multiple bioactivities,
especially, the aphicidal activity. To find a biostable and bioactive insecticide
candidate with simplified structure, a series of N-terminal modified insect kinin
analogs was designed and synthesized based on the lead compound [Aib]-Phe-Phe
[Aib]-Trp-Gly-NH2. Their aphicidal activity against the soybean aphid Aphis
glycines was evaluated. The results showed that all the analogs maintained the
aphicidal activity. In particular, the aphicidal activity of the pentapeptide
analog X Phe-Phe-[Aib]-Trp-Gly-NH2 (LC50=0.045mmol/L) was similar to the lead
compound (LC50=0.048mmol/L). This indicated that the N-terminal protective group
may not play an important role in the activity and the analogs structure could be
simplified to pentapeptide analogs while retaining good aphicidal activity. The
core pentapeptide analog X can be used as the lead compound for further chemical
modifications to discover potential insecticides.
PMID- 25116630
TI - Terminal sialic acids on CD44 N-glycans can block hyaluronan binding by forming
competing intramolecular contacts with arginine sidechains.
AB - Specific sugar residues and their linkages form the basis of molecular
recognition for interactions of glycoproteins with other biomolecules. Seemingly
small changes, like the addition of a single monosaccharide in the covalently
attached glycan component of glycoproteins, can greatly affect these
interactions. For instance, the sialic acid capping of glycans affects protein
ligand binding involved in cell-cell and cell-matrix interactions. CD44 is a
single-pass transmembrane glycoprotein whose binding with its carbohydrate ligand
hyaluronan (HA), an extracellular matrix component, mediates processes such as
leukocyte homing, cell adhesion, and tumor metastasis. This binding is highly
regulated by glycosylation of the N-terminal extracellular hyaluronan-binding
domain (HABD); specifically, sialic acid capped N-glycans of HABD inhibit ligand
binding. However, the molecular mechanism behind this sialic acid mediated
regulation has remained unknown. Two of the five N-glycosyation sites of HABD
have been previously identified as having the greatest inhibitory effect on HA
binding, but only if the glycans contain terminal sialic acid residues. These two
sites, Asn25 and Asn120, were chosen for in silico glycosylation in this study.
Here, from extensive standard molecular dynamics simulations and biased
simulations, we propose a molecular mechanism for this behavior based on
spontaneously-formed charge-paired hydrogen bonding interactions between the
negatively-charged sialic acid residues and positively-charged Arg sidechains
known to be critically important for binding to HA, which itself is negatively
charged. Such intramolecular hydrogen bonds would preclude associations critical
to hyaluronan binding. This observation suggests how CD44 and related
glycoprotein binding is regulated by sialylation as cellular environments
fluctuate.
PMID- 25116634
TI - Toward an effective long-term strategy for preventing motor vehicle crashes and
injuries.
AB - Casualties due to motor vehicle crashes (MVCs) include some 40,000 deaths each
year in the United States and one million deaths worldwide. One strategy that has
been recommended for improving automobile safety is to lower speed limits and
enforce them with speed cameras. However, motor vehicles can be hazardous even at
low speeds whereas properly protected human beings can survive high-speed crashes
without injury. Emphasis on changing driver behavior as the focus for road safety
improvements has been largely unsuccessful; moreover, drivers today are
increasingly distracted by secondary tasks such as cell phone use and texting.
Indeed, the true limiting factor in vehicular safety is the capacity of human
beings to sense and process information and to make rapid decisions. Given that
dramatic reductions in injuries and deaths from MVCs have occurred over the past
century due to improvements in safety technology, despite increases in the number
of vehicles on the road and miles driven per vehicle, we propose that an
effective long-term strategy for reducing MVC-related injury would be continued
technological innovation in vehicle design, aimed at progressively removing the
driver from routine operational decision-making. Once this is achieved, high
rates of speed could be achieved on open highways, with minimal risk of crashes
and injury to occupants and pedestrians.
PMID- 25116635
TI - Global monitoring of water supply and sanitation: history, methods and future
challenges.
AB - International monitoring of drinking water and sanitation shapes awareness of
countries' needs and informs policy, implementation and research efforts to
extend and improve services. The Millennium Development Goals established global
targets for drinking water and sanitation access; progress towards these targets,
facilitated by international monitoring, has contributed to reducing the global
disease burden and increasing quality of life. The experiences of the MDG period
generated important lessons about the strengths and limitations of current
approaches to defining and monitoring access to drinking water and sanitation.
The methods by which the Joint Monitoring Programme (JMP) of WHO and UNICEF
tracks access and progress are based on analysis of data from household surveys
and linear regression modelling of these results over time. These methods provide
nationally representative and internationally comparable insights into the
drinking water and sanitation facilities used by populations worldwide, but also
have substantial limitations: current methods do not address water quality,
equity of access, or extra-household services. Improved statistical methods are
needed to better model temporal trends. This article describes and critically
reviews JMP methods in detail for the first time. It also explores the impact of,
and future directions for, international monitoring of drinking water and
sanitation.
PMID- 25116636
TI - The association between season of pregnancy and birth-sex among Chinese.
AB - OBJECTIVE: although numerous studies have reported the association between birth
season and sex ratio, few studies have been conducted in subtropical regions in a
non-Western setting. The present study assessed the effects of pregnancy season
on birth sex ratio in China. METHODS: We conducted a national population-based
retrospective study from 2006-2008 with 3175 children-parents pairs enrolled in
the Northeast regions of China. Demographics and data relating to pregnancy and
birth were collected and analyzed. A multiple logistical regression model was
fitted to estimate the regression coefficient and 95% confidence interval (CI) of
refractive error for mother pregnancy season, adjusting for potential
confounders. RESULTS: After adjusting for parental age (cut-off point was 30
years), region, nationality, mother education level, and mother miscarriage
history, there is a significant statistical different mother pregnancy season on
birth-sex. Compared with mothers who were pregnant in spring, those pregnant in
summer or winter had a high probability of delivering girls (p < 0.05). The birth
sex ratio varied with months. CONCLUSIONS: Our results suggested that mothers
pregnant in summer and winter were more likely to deliver girls, compared with
those pregnant in spring. Pregnancy season may play an important role in the
birth-sex.
PMID- 25116638
TI - Haptic discrimination of distance.
AB - While quite some research has focussed on the accuracy of haptic perception of
distance, information on the precision of haptic perception of distance is still
scarce, particularly regarding distances perceived by making arm movements. In
this study, eight conditions were measured to answer four main questions, which
are: what is the influence of reference distance, movement axis, perceptual mode
(active or passive) and stimulus type on the precision of this kind of distance
perception? A discrimination experiment was performed with twelve participants.
The participants were presented with two distances, using either a haptic device
or a real stimulus. Participants compared the distances by moving their hand from
a start to an end position. They were then asked to judge which of the distances
was the longer, from which the discrimination threshold was determined for each
participant and condition. The precision was influenced by reference distance. No
effect of movement axis was found. The precision was higher for active than for
passive movements and it was a bit lower for real stimuli than for rendered
stimuli, but it was not affected by adding cutaneous information. Overall, the
Weber fraction for the active perception of a distance of 25 or 35 cm was about
11% for all cardinal axes. The recorded position data suggest that participants,
in order to be able to judge which distance was the longer, tried to produce
similar speed profiles in both movements. This knowledge could be useful in the
design of haptic devices.
PMID- 25116639
TI - The four-year course of major depressive disorder: the role of staging and risk
factor determination.
AB - BACKGROUND: Much is still unclear about the mechanisms underlying the course of
major depressive disorder (MDD). This study aimed to identify risk factors that
predict a poor prognosis of MDD while taking into consideration its chronicity at
baseline. METHODS: In patients with MDD (n = 767), we examined whether baseline
clinical factors, sociodemographics, childhood trauma, personality and life
events predicted the 4-year course (i.e., sustained recovery, temporary recovery
and chronic course) of MDD. Baseline chronicity of MDD was taken into account by
testing whether associations were different for patients with nonchronic versus
chronic MDD at baseline. RESULTS: In patients with nonchronic MDD at baseline,
27.8% developed a chronic disorder during follow-up, whereas 53.0% of patients
with chronic MDD at baseline had a persistent chronic disorder during follow-up.
Severity of MDD, childhood trauma and greater age were important general risk
factors for a poor prognosis, independent of MDD chronicity at baseline. In
contrast, low extraversion was only important for the course of nonchronic MDD at
baseline, while higher education and negative life events (in patients with high
neuroticism) were only relevant for the course of chronic MDD at baseline.
CONCLUSIONS: One out of 4 patients with nonchronic MDD progressed to a chronic
disorder, while half of the patients with chronic MDD remained chronic during
follow-up. Since several risk factors for a poor prognosis differed for patients
with nonchronic and chronic MDD at baseline, treatment targets should be adjusted
for current chronicity of MDD.
PMID- 25116637
TI - Toxicological effects of nickel chloride on IgA+ B Cells and sIgA, IgA, IgG, IgM
in the intestinal mucosal immunity in broilers.
AB - The objective of this study was to investigate the toxicological effects of
dietary NiCl2 on IgA+ B cells and the immunoglobulins including sIgA, IgA, IgG
and IgM in the small intestine and cecal tonsil of broilers by the methods of
immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Two hundred
and forty one-day-old avian broilers were randomly divided into four groups and
fed on a control diet and three experimental diets supplemented with 300, 600,
and 900 mg/kg NiCl2 for 42 days. Compared with the control group, the IgA+ B cell
number and the sIgA, IgA, IgG, and IgM contents in the NiCl2-treated groups were
significantly decreased (p < 0.05 or p < 0.01). It was concluded that dietary
NiCl2 in the excess of 300 mg/kg had negative effects on the IgA+ B cell number
and the above mentioned immunoglobulin contents in the small intestine and the
cecal tonsil. NiCl2-reduced sIgA, IgA, IgG and IgM contents is due to decrease in
the population and/or the activation of B cell. The results suggest that NiCl2 at
high levels has intestinal mucosal humoral immunotoxicity in animals.
PMID- 25116641
TI - Distribution of potato spindle tuber viroid in reproductive organs of petunia
during its developmental stages.
AB - Embryo infection is important for efficient seed transmission of viroids. To
identify the major pattern of seed transmission of viroids, we used in situ
hybridization to histochemically analyze the distribution of Potato spindle tuber
viroid (PSTVd) in each developmental stage of petunia (flowering to mature seed
stages). In floral organs, PSTVd was present in the reproductive tissues of
infected female * infected male and infected female * healthy male but not of
healthy female * infected male before embryogenesis. After pollination, PSTVd was
detected in the developed embryo and endosperm in all three crosses. These
findings indicate that PSTVd is indirectly delivered to the embryo through ovule
or pollen during the development of reproductive tissues before embryogenesis but
not directly through maternal tissues as cell-to-cell movement during
embryogenesis.
PMID- 25116642
TI - Molecular genetic analysis of cucumber mosaic virus populations infecting pepper
suggests unique patterns of evolution in Korea.
AB - Studying genetic structure and diversity of viruses is important to understand
the evolutionary mechanisms that generate and maintain variations in viral
populations. Cucumber mosaic virus (CMV) is endemic in most pepper fields in
Korea. Currently, no effective methods for control of CMV are available due to
many environmental and biological factors such as the extensive evolutionary
capacity of CMV. Thus, analyzing the genetic structure of CMV populations may
facilitate the development of strategies for the control of CMV. In this study,
252 pepper (Capsicum annuum) samples showing virus symptoms were collected by
field surveys performed throughout Korea in 2007. Reverse-transcription
polymerase chain reaction analyses revealed that, in total, 165 collected samples
were infected with CMV. Forty-five CMV isolates were randomly selected within
each regional subpopulation and analyzed by full-genome sequencing. Analyses of
genetic diversity showed that the 2b gene of CMV is under weaker purifying
selection than the other genes. Based on the phylogenetic analysis of RNA1, the
CMV isolates from pepper were divided into three clusters in subgroup I. Our full
genome sequence-based molecular analyses of the CMV Korean population suggest
that the subpopulations of CMV have been geographically localized in pepper
fields in Korea.
PMID- 25116643
TI - Pollen transmission of asparagus virus 2 (AV-2) may facilitate mixed infection by
two AV-2 isolates in asparagus plants.
AB - Asparagus virus 2 (AV-2) is a member of the genus Ilarvirus and thought to induce
the asparagus decline syndrome. AV-2 is known to be transmitted by seed, and the
possibility of pollen transmission was proposed 25 years ago but not verified. In
AV-2 sequence analyses, we have unexpectedly found mixed infection by two
distinct AV-2 isolates in two asparagus plants. Because mixed infections by two
related viruses are normally prevented by cross protection, we suspected that
pollen transmission of AV-2 is involved in mixed infection. Immunohistochemical
analyses and in situ hybridization using AV-2-infected tobacco plants revealed
that AV-2 was localized in the meristem and associated with pollen grains. To
experimentally produce a mixed infection via pollen transmission, two Nicotiana
benthamiana plants that were infected with each of two AV-2 isolates were
crossed. Derived cleaved-amplified polymorphic sequence analysis identified each
AV-2 isolate in the progeny seedlings, suggesting that pollen transmission could
indeed result in a mixed infection, at least in N. benthamiana.
PMID- 25116644
TI - Co-C dissociation of adenosylcobalamin (coenzyme B12): role of dispersion,
induction effects, solvent polarity, and relativistic and thermal corrections.
AB - Quantum-chemical cluster modeling is challenged in the limit of large, soft
systems by the effects of dispersion and solvent, and well as other physical
interactions. Adenosylcobalamin (AdoCbl, coenzyme B12), as one of the most
complex cofactors in life, constitutes such a challenge. The cleavage of its
unique organometallic Co-C bond has inspired multiple studies of this cofactor.
This paper reports the fully relaxed potential energy surface of Co-C cleavage of
AdoCbl, including for the first time all side-chain interactions with the
dissociating Ado group. Various methods and corrections for dispersion,
relativistic effects, solvent polarity, basis set superposition error, and
thermal and vibrational effects were investigated, totaling more than 550 single
point energies for the large model. The results show immense variability
depending on method, including solvation, functional type, and dispersion,
challenging the conceived accuracy of methods used for such systems. In
particular, B3LYP-D3 seems to severely underestimate the Co-C bond strength,
consistent with previous results, and BP86 remains accurate for cobalamins when
dispersion interactions are accounted for.
PMID- 25116645
TI - Dual drug release from core-shell nanoparticles with distinct release profiles.
AB - Multiple drug combination is a promising strategy in biomedical fields, such as
cancer chemotherapy and tissue engineering. With the aim of codelivering multiple
drugs with different characteristics, immiscible and miscible liquids were
utilized to fabricate nanoparticles of polyvinylpyrrolidone/poly(lactic-co
glycolic acid) (PLGA) and poly(epsilon-caprolactone)/PLGA with distinct core
shell structure by coaxial electrospray. Each kind of nanoparticles can
encapsulate the hydrophilic rhodamine B and hydrophobic naproxen in one single
step efficiently. Encapsulation efficiency was over 85%. The different release
patterns of dual-drug encapsulated were demonstrated when the drug location
swapped, attributing to the distinct core-shell structures of nanoparticles and
the interaction between drug molecules and carrier polymers. Meanwhile, the
release profiles of encapsulated drugs with different loading amount were
investigated as well. Dual drug release profiles from nanoparticles were affected
by the unique architecture of nanocarriers (porous and core-shell structure),
physical properties of polymers, and drugs. In addition, polymer-drug and drug
drug molecular interaction may take an important role in drug release behaviors.
The results suggested that the distinct release kinetics of multiple drugs
fabricated by coaxial electrospray can be obtained and tuned to fulfill the
clinical requirement in combination therapy.
PMID- 25116646
TI - Energy transfer on demand: photoswitch-directed behavior of metal-porphyrin
frameworks.
AB - In this paper, a photochromic diarylethene-based derivative that is
coordinatively immobilized within an extended porphyrin framework is shown to
maintain its photoswitchable behavior and to direct the photophysical properties
of the host. In particular, emission of a framework composed of bis(5-pyridyl-2
methyl-3-thienyl)cyclopentene (BPMTC) and tetrakis(4-carboxyphenyl)porphyrin
(H4TCPP) ligands anchored by Zn(2+) ions can be altered as a function of incident
light. We attribute the observed cyclic fluorescence behavior of the synthesized
porphyrin-BPMTC array to activation of energy transfer (ET) pathways through
BPMTC photoisomerization. Time-resolved photoluminescence measurements show a
decrease in average porphyrin emission lifetime upon BPMTC insertion, consistent
with an ET-based mechanism. These studies portend the possible utilization of
photochromic ligands to direct chromophore behavior in large light-harvesting
ensembles.
PMID- 25116647
TI - Are insights from Indigenous health shaping a paradigm shift in health promotion
praxis in Australia?
AB - Health promotion really is at a cross-road. Traditionally guided by the Ottawa
Charter, it has been thought of as principle-guided actions, processes and
technique, as well as outcomes or results. Health promotion has been
characterised by its products and some even call it theory. In Australia, public
funding for health promotion has, for many years, shaped its practice into
behaviour change interventions. However, governments around the country are
reconsidering their investments, evidenced by ideologically motivated policy
shifts and associated substantial funding cuts. Recently, themes of empowerment,
community control and community agency have emerged as new directions for future
health promotion praxis and reports of activism-based approaches that seek to
mobilise community energies around sexual health inequity have started to appear
in the literature. Noting parallel developments in the social determinants and
social change discourses, this paper posits that cutting edge health promotion
efforts by Indigenous communities in Australia are shaping a new approach with
potentially global application.
PMID- 25116648
TI - Using kinematics and a dynamical systems approach to enhance understanding of
clinically observed aberrant movement patterns.
AB - The objective of this technical paper is to demonstrate how graphing kinematic
data to represent body segment coordination and control can assist clinicians and
researchers in understanding typical and aberrant human movement patterns.
Aberrant movements are believed to be associated with musculoskeletal pain and
dysfunction. A dynamical systems approach to analysing movement provides a useful
way to study movement control and coordination. Continuous motion angle-angle and
coupling angle-movement cycle graphs provide information about coordinated
movement between body segments, whereas phase-plane graphs provide information
about neuromuscular control of a body segment. Examples demonstrate how a
dynamical systems approach can be used to represent (1) typical movement patterns
of the lumbopelvic and shoulder regions; (2) aberrant coordination in an
individual with low back pain who presented with altered lumbopelvic rhythm; and
(3) aberrant control of shoulder movement in an individual with observed scapular
dysrhythmia. Angle-angle and coupling angle-movement cycle graphs were consistent
with clinical operational definitions of typical and altered lumbopelvic rhythm.
Phase-plane graphs illustrated differences in scapular control between
individuals having typical scapular motion and an individual with scapular
dysrhythmia. Angle-angle, coupling angle-movement cycle, and phase-plane graphs
provide information about the amount and timing of segmental motion, which
clinicians assess when they observe movements. These approaches have the
potential to (1) enhance understanding of typical and aberrant movement patterns;
(2) assist with identifying underlying movement impairments that contribute to
aberrant movements: and (3) improve clinicians' ability to visually assess and
categorize functional movements.
PMID- 25116651
TI - Luminescent and transparent nanopaper based on rare-earth up-converting
nanoparticle grafted nanofibrillated cellulose derived from garlic skin.
AB - Highly flexible, transparent, and luminescent nanofibrillated cellulose (NFC)
nanopaper with heterogeneous network, functionalized by rare-earth up-converting
luminescent nanoparticles (UCNPs), was rapidly synthesized by using a moderate
pressure extrusion paper-making process. NFC was successfully prepared from
garlic skin using an efficient extraction approach combined with high frequency
ultrasonication and high pressure homogenization after removing the noncellulosic
components. An efficient epoxidation treatment was carried out to enhance the
activity of the UCNPs (NaYF4:Yb,Er) with oleic acid ligand capped on the surface.
The UCNPs after epoxidation then reacted with NFC in aqueous medium to form UCNP
grafted NFC nanocomposite (NFC-UCNP) suspensions at ambient temperature. Through
the paper-making process, the assembled fluorescent NFC-UCNP hybrid nanopaper
exhibits excellent properties, including high transparency, strong up-conversion
luminescence, and good flexibility. The obtained hybrid nanopaper was
characterized by transmission electron microscopy (TEM), atomic force microscope
(AFM), Fourier transform infrared spectroscopy (FTIR), field emission-scanning
electron microscope (FE-SEM), up-conversion luminescence (UCL) spectrum, and
ultraviolet and visible (UV-vis) spectrophotometer. The experimental results
demonstrate that the UCNPs have been successfully grafted to the NFC matrix with
heterogeneous network. And the superiorly optical transparent and luminescent
properties of the nanopaper mainly depend on the ratio of UCNPs to NFC. Of
importance here is that, NFC and UCNPs afford the nanopaper a prospective
candidate for multimodal anti-counterfeiting, sensors, and ion probes
applications.
PMID- 25116649
TI - Effector-dependent neglect and splenial disconnection: a spherical deconvolution
tractography study.
AB - We present the case of a patient with left homonymous hemianopia and chronic left
neglect consequent to a stroke in the occipito-temporal regions of the right
hemisphere. When the patient performed cancellation tasks with her right
(dominant) hand, she had severe and persistent left neglect at retest 7 and 8
years after onset. However, her performance on line bisection was invariably
within normal limits. Strikingly, performance on cancellation tests reverted to
normal when the patient used her left hand. White matter tractography using
spherical deconvolution demonstrated damage to the splenium of the corpus
callosum, as well as a relative preservation of the right fronto-parietal
network. Effector-dependent neglect may occur because splenial disconnection
deprives the right fronto-parietal network from visual information processed by
the left hemisphere. Consequently, spatial exploration reverts to normal when the
patient uses her left hand, thus involving more directly the fronto-parietal
attentional networks in the right-hemisphere.
PMID- 25116652
TI - Food beliefs and practices during pregnancy in Ghana: implications for maternal
health interventions.
AB - Ghanaian women's food beliefs and practices during pregnancy and the scope for
developing more effective maternal health interventions were explored in this
study. Thirty-five multiethnic Ghanaian women between the ages of 29 and 75 were
interviewed about pregnancy food beliefs and practices. I show that, based on the
data analysis, their knowledge about food was drawn from lifeworlds (family and
friends), educational settings, health professionals, mass media, and body-self
knowledge (unique pregnancy experiences). Core lay ideas converged with expert
knowledge on maternal health nutrition. Multiple external factors (e.g.,
economics, cultural representations of motherhood) and internal factors (e.g.,
the unpredictable demands of the pregnant body) influenced pregnancy food
practices. I suggest and discuss a need for culturally situated multilevel
interventions.
PMID- 25116653
TI - Water adsorption in UiO-66: the importance of defects.
AB - Simulated adsorption isotherms for water in UiO-66 illustrate that defects in the
form of missing linkers make this MOF more hydrophilic. Heats of adsorption and
density plots further confirm the effect of defects on adsorption of water in UiO
66 at low loadings. In addition, water and CO2 isotherms indicate that not only
the amount of defects but their locations within the material affect the loading
of guest molecules.
PMID- 25116650
TI - A magnetic carbon sorbent for radioactive material from the Fukushima nuclear
accident.
AB - Here we present the first report of a carbon-gamma-Fe2O3 nanoparticle composite
of mesoporous carbon, bearing COOH- and phenolic OH- functional groups on its
surface, a remarkable and magnetically separable adsorbent, for the radioactive
material emitted by the Fukushima Daiichi nuclear power plant accident.
Contaminated water and soil at a level of 1,739 Bq kg(-1) ((134)Cs and (137)Cs at
509 Bq kg(-1) and 1,230 Bq kg(-1), respectively) and 114,000 Bq kg(-1) ((134)Cs
and (137)Cs at 38,700 Bq kg(-1) and 75,300 Bq kg(-1), respectively) were
decontaminated by 99% and 90% respectively with just one treatment carried out in
Nihonmatsu city in Fukushima. Since this material is remarkably high performance,
magnetically separable, and a readily applicable technology, it would reduce the
environmental impact of the Fukushima accident if it were used.
PMID- 25116655
TI - Supervision in neuropsychological assessment: a survey of training, practices,
and perspectives of supervisors.
AB - Within the psychology supervision literature, most theoretical models and
practices pertain to general clinical or counseling psychology. Supervision
specific to clinical neuropsychology has garnered little attention. This survey
study explores supervision training, practices, and perspectives of
neuropsychology supervisors. Practicing neuropsychologists were invited to
participate in an online survey via listservs and email lists. Of 451
respondents, 382 provided supervision to students, interns, and/or fellows in
settings such as VA medical centers (37%), university medical centers (35%), and
private practice (15%). Most supervisors (84%) reported supervision was discussed
in graduate school "minimally" or "not at all." Although 67% completed informal
didactics or received continuing education in supervision, only 27% reported
receiving training specific to neuropsychology supervision. Notably, only 39%
were satisfied with their training in providing supervision and 77% indicated
they would likely participate in training in providing supervision, if available
at professional conferences. Results indicate that clinical neuropsychology as a
specialty has paid scant attention to developing supervision models and explicit
training in supervision skills. We recommend that the specialty develop models of
supervision for neuropsychological practice, supervision standards and
competencies, training methods in provision of supervision, and benchmark
measures for supervision competencies.
PMID- 25116656
TI - Bit-related lesions in Icelandic competition horses.
AB - BACKGROUND: Oral lesions related to the use of the bit and bridle are reported to
be common findings in horses worldwide and represent an important animal welfare
issue. In order to provide an overview of bit-related lesions in Icelandic
competition horses, a field examination of the rostral part of the oral cavity
was performed in 424 competition horses coming to the two major national horse
events in Iceland in 2012. Records from repeated examination of 77 horses prior
to the finals were used to assess potential risk factors. RESULTS: Mild lesions
were recorded in 152 horses (36%) prior to the preliminary rounds. They were most
often located in the commissures of the lips and the adjacent buccal mucosa
(n=111). Severe lesions were found in 32 (8%) horses. For 77 horses examined
prior to the finals, the frequency of findings in the area of the mandibular
interdental space (bars of the mandible) had increased from 8% to 31% (P<0.0001).
These findings were most often (16/24) regarded as severe. The presence of
lesions on the bars was strongly associated to the use of curb bits with a port
(OR=75, P=0.009). CONCLUSIONS: Bit-related lesions were found to be a general
problem in Icelandic competition horses. The type of bits used influenced both
the location and the severity of the lesions. The use of curb bits with a port
was found to be a decisive risk factor for lesions on the bars of the mandible,
most of which were regarded as severe. The results also raised questions about
the head and neck carriage demanded for the competition horses.
PMID- 25116657
TI - Dynamic propensity as an indicator of heterogeneity in room-temperature ionic
liquids.
AB - We investigate the dynamic propensity in a coarse-grained model of a room
temperature ionic liquid via molecular dynamics simulations. Dynamic propensity
is defined as the average of squared displacements for each ion during a given
time interval over the isoconfigurational ensemble. As the temperature is
lowered, distributions of the dynamic propensity develop fat tails at high
values, indicating the presence of dynamic heterogeneity in the system. The
increase in the heterogeneity for the cation is more evident than that for the
anion, and a high propensity exhibits a large variance in the isoconfigurational
ensemble, implying that dynamic propensity is related to ions' motions at a large
length scale, rather than a direct measure of the individual ion dynamics. In
addition, large non-Gaussian parameters observed for small dynamic propensities
reveal intermittent dynamical behaviors of ions. In order to reveal the origin of
the dynamic heterogeneity in a room-temperature ionic liquid, a possible
correlation between the mobility and dynamic propensity is further probed. It is
observed that spatial distributions of the dynamic propensity coincide with those
of the mobility. The results suggest a possible connection between the structure
and heterogeneous dynamics on large length scales.
PMID- 25116658
TI - Gram-negative infections in pediatric and neonatal intensive care units of Latin
America.
AB - In order to review the epidemiology of Gram-negative infections in the pediatric
and neonatal intensive care units (PICUs and NICUs) of Latin America a systematic
search of PubMed and targeted search of SciELO was performed to identify relevant
articles published since 2005. Independent cohort data indicated that overall
infection rates were higher in Latin American PICUs and NICUs versus developed
countries (range, 5%-37% vs 6%-15%, respectively). Approximately one third of
Latin American patients with an acquired PICU or NICU infection died, and crude
mortality was higher among extremely low-birth-weight infants and those with an
infection caused by Gram-negative bacteria. In studies reporting > 100 isolates,
the frequency of Gram-negative pathogens varied from 31% (Colombia) to 63%
(Mexico), with Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia
coli the predominant pathogens in almost all countries, and Acinetobacter spp.
and Serratia spp. isolated sporadically. The activity of quinolones and third
generation cephalosporins against P. aeruginosa, Acinetobacter spp., and
Enterobacteria was seriously compromised, coincident with a high prevalence of
circulating extended-spectrum beta-lactamases. Furthermore, we identified two
observational studies conducted in Chile and Brazil reporting infections by P.
aeruginosa and Acinetobacter baumannii in PICUs, demonstrating resistance to
carbapenems, and two outbreaks of carbapenem-resistant K. pneumoniae in Colombia
and Brazil. The endemicity of multidrug-resistant Gram-negative infections in
Latin American PICUs and NICUs is punctuated by intermittent clonal outbreaks.
The problem may be alleviated by ensuring ICUs are less crowded, increasing
staffing levels of better-trained health care personnel, and implementing
antimicrobial stewardship and surveillance programs.
PMID- 25116659
TI - An overview of extended-spectrum beta-lactamases in veterinary medicine and their
public health consequences.
AB - Serious human and animal infections caused by bacteria are usually treated with
beta-lactams. Extended-spectrum beta-lactamases (ESBLs) constitute the most
clinically and economically important enzymes that are able to hydrolyze and
inactivate beta-lactam antibiotics in veterinary medicine. The spread of ESBLs
represents a serious threat to healthcare systems, drastically undermining
therapeutic options. The relationship between drug usage and the emergence of
resistance has been extensively reported. Nevertheless, the use of antimicrobials
in veterinary medicine and the emergence of ESBLs in animals remains a matter of
debate. Moreover, there is still controversy about whether antibiotic usage in
farm animals poses a potential public health risk. This review will (i) deal with
aspects related to the presence of ESBLs in veterinary medicine, (ii) its link
with human medicine, and (iii) discuss strategies to be implemented to preserve
antimicrobial effectiveness. New insights relative to old questions concerning
antimicrobial use in domestic animals are also presented.
PMID- 25116660
TI - Diagnosis of leishmaniasis.
AB - Leishmaniasis is a clinically heterogeneous syndrome caused by intracellular
protozoan parasites of the genus Leishmania. The clinical spectrum of
leishmaniasis encompasses subclinical (not apparent), localized (skin lesion),
and disseminated (cutaneous, mucocutaneous, and visceral) infection. This
spectrum of manifestations depends on the immune status of the host, on the
parasite, and on immunoinflammatory responses. Visceral leishmaniasis causes high
morbidity and mortality in the developing world. Reliable laboratory methods
become mandatory for accurate diagnosis, especially in immunocompromised patients
such as those infected with HIV. In this article, we review the current state of
the diagnostic tools for leishmaniasis, especially the serological test.
PMID- 25116661
TI - Antimicrobial and molecular analysis of Salmonella serovar Livingstone strains
isolated from humans in Tunisia and Belgium.
AB - INTRODUCTION: Salmonella Livingstone is one of the most common serotypes
responsible for nosocomial outbreaks in Tunisia. In this study, 42 isolates of
Salmonella Livingstone were analyzed. Most of these were isolated from humans (31
strains from Tunisia and 9 strains from Belgium) and 2 isolates came from food
products (beef and pork). METHODOLOGY: All strains were characterized by
antibiogram, multilocus sequence typing (MLST), and virulotyping. This last
technique was carried out by simple PCR of five chromosomal genes (agfA, hin/H2,
iroB, phoP/Q, and slyA) and two plasmid genes (spvA and spvC). RESULTS: All
Tunisian strains were resistant to amoxicillin, amoxicillin-clavulanic acid,
ticarcillin, cefalotin, gentamicin, and kanamycin. They were also resistant to
third-generation cephalosporin antibiotics (cefotaxim and ceftazidim). Belgian
isolates were susceptible to all antibiotics tested. Further to MLST analyses,
Tunisian strains belonged to the same sequence type, ST543. For Belgian isolates,
eight strains had a ST543 profile, two strains had a ST638 profile, and one
strain had a ST457 profile. Analyses of the virulence gene contents showed that
strains isolated in different years and from different origins had the same
virulence profile. These carried all five chromosomal genes and lacked plasmid
located virulence genes spvA and spvC. CONCLUSIONS: A combination of different
typing methods showed that the majority of Belgian strains and all Tunisian
strains were closely related; they belonged to the same sequence type (ST543) and
had the same virulence profile, but different antibiotic resistance profiles
depended on the country of origin.
PMID- 25116662
TI - A three-year review of antimicrobial resistance of Salmonella enterica serovars
Typhi and Paratyphi A in Pakistan.
AB - INTRODUCTION: Enteric fever is among the most common bacteraemic illnesses in
South Asia. Multidrug resistance as well as fluoroquinolone resistance has
severely limited therapeutic options in high disease burden countries such as
Pakistan. This review was conducted to determine the frequency of drug-resistant
Salmonella enterica serovar Typhi (S.Typhi) and Salmonella enterica serovar
Paratyphi A (S. Paratyphi A) between 2009 and 2011. METHODOLOGY: This study was a
review of laboratory data. The antibiotic susceptibility of typhoidal Salmonellae
isolated from blood cultures submitted to the Aga Khan University Hospital's
laboratory from all over Pakistan between January 2009 and December 2011 were
reviewed. RESULTS: The sensitivity data of 4,323 positive isolates of S. Typhi
and S. Paratyphi A isolated during the three-year period were reviewed. The
majority of isolates were S. Typhi (59.6%).Over three years, the incidence of
multidrug-resistant (MDR) S.Typhi remained high, ranging from 64.8%-66.0%, while
MDR S. Paratyphi A decreased from 4.2% to 0.6%. Fluoroquinolone resistance
increased for S. Typhi from 84.7% to 91.7%. Cefixime- and ceftriaxone-resistant
S. Typhi were isolated in two children. CONCLUSIONS: Our results show high rates
of multidrug and fluoroquinolone resistance among S. Typhi and S. Paratyphi. The
occurrence of two cases of ceftriaxone resistance is alarming.
PMID- 25116663
TI - Low rifampicin concentrations in tuberculosis patients with HIV infection.
AB - INTRODUCTION: The efficacy of tuberculosis (TB) treatment in Human
Immunodeficiency Syndrome (HIV) co-infected patients may be compromised by
genetic and pharmacokinetic variation in drug disposition. Rifampicin is a
critical component of TB treatment. We investigated the influence of drug
transporter gene polymorphisms on rifampicin concentrations in TB-HIV co-infected
patients in Durban, South Africa. METHODOLOGY: Rifampicin concentrations were
measured 2.5 hours post-dose (approximated peak, C2.5 hr) in patients receiving
either 450mg or 600mg rifampicin, randomized to either integrated or sequential
antiretroviral treatment. Patients were genotyped for SLCO1B1 (rs4149032)
polymorphisms. A mixed effects regression model was fitted to assess the
influence of various factors on rifampicin concentrations. TB recurrence rates
were also estimated. RESULTS: In 57 patients, median (IQR) C2.5 hr was 3.6 (2.8
5.0) ug/mL. Polymorphism frequency in the SLCO1B1 (rs4149032) drug transporter
gene was high (0.76) and was associated with low median rifampicin C2.5 hr, 3.7
(2.8-5.0) ug/mL in the heterozygous and 3.4 (2.7-4.7) ug/mL in the homozygous
variant carriers. Concentrations were also low in males (p < 0.0001) and those
with low haemoglobin (p = 0.02). Although reinfection could not be distinguished
from reactivation for the 43 patients followed post trial, the incidence of TB
recurrence was 7.1 per 100 person-years. Of the eight patients in whom TB
recurred, seven had the polymorphism. CONCLUSION: Approximated peak rifampicin
concentrations were well below the recommended target range of 8 to 24 ug/mL in
this patient population with its high frequency of the SLCO1B1 (rs4149032)
polymorphism. Increased rifampicin dosage may be warranted in African, HIV- TB co
infected patients.
PMID- 25116664
TI - Oropharyngeal tularemia cases admitted to a military hospital in Ankara, Turkey.
AB - INTRODUCTION: This study aimed to review the possible sources of infection of 16
oropharyngeal tularemia hospital cases, and to document their epidemiological and
demographical characteristics, laboratory findings, treatment methods, and
treatment results. METHODOLOGY: Sixteen cases from a Turkish military hospital
between January 2011 and December 2012 were retrospectively evaluated. The age,
sex, occupation, place of residence, symptoms, duration of symptoms, laboratory
results, treatment and duration, and treatment results were recorded. Tularemia
was diagnosed through tularemia-specific tests once the other conditions that may
have caused lymphadenopathy were excluded. RESULTS: Twelve of the patients
included in this study were males. The average age of the patients was 32.1 +/-
17.2 years. Sore throat, fatigue, and fever were the most frequent symptoms. The
mean duration of symptoms was 21.6 +/- 6.9 days. All the patients had been
treated for tonsillopharyngitis in primary healthcare institutions previously.
However, despite the treatment, cervical lymphadenopathy had developed in these
cases. Patients were given streptomycin, doxycycline, and ciprofloxacin
monotherapy or in combination. Ten of the cases fully recovered, while five
required surgical lymph node drainage. Spontaneous drainage occurred in the
single remaining case. CONCLUSIONS: Turkey is considered to be an endemic country
with regards to tularemia. Prompt diagnosis and proper treatment of the disease
is imperative in providing cure. Since it can be potentially confused with
tuberculous lymphadenitis, differential diagnosis is vital. Patients presenting
with a condition of tonsillopharyngitis in endemic areas must be carefully
monitored.
PMID- 25116665
TI - Clinical characteristics and risk factors of infections caused by
Stenotrophomonas maltophilia in a hospital in northwest China.
AB - INTRODUCTION: Stenotrophomonas maltophilia infections have recently increased in
importance in China, particularly in intensive care units (ICUs). The aim of this
study was to investigate the clinical characteristics and risk factors of S.
maltophilia infection in ICU of a hospital in northwest China. METHODOLOGY: The
characteristics and outcomes of patients with any type of S. maltophilia
infection at Shaanxi Provincial People's Hospital, Shaanxi, China, over a two
year period (from July 2011 to June 2013) were studied. S. maltophilia
antimicrobial susceptibility was tested with the agar dilution method. The risk
factors for all-cause in-hospital mortality were assessed with multivariate
logistic regression. RESULTS: Forty patients (median age, 72 years; 77.5% males)
with S. maltophilia infection were identified. The main type of infection was
lower respiratory tract infection (97.5%); one patient had a bloodstream
infection. A total of 97.5% patients were infected with two or more organisms at
the same time. The main characteristics of the patients were prolonged use of
mechanical ventilation, urethral catheter, and central venous catheter before the
infections occurred. The case number of infection was not different in the four
seasons. High in vitro sensitivity was observed to minocycline (91.2%),
levofloxacin (85.3%), and trimethoprim-sulfamethoxazole (79.4%). Most patients
received therapy with a combination of agents. The crude mortality was 50%. By
multivariate analysis, low albumin content and hypotension were the independent
prognostic factors for mortality. CONCLUSIONS: Appropriate antimicrobial
treatment had no positive impact on mortality. The impacts of albumin supplements
and increasing blood pressure on mortality require further clinical studies.
PMID- 25116666
TI - Sexual behavioral correlates with HSV-2 seroprevalence among pregnant women in
Nigeria.
AB - INTRODUCTION: The burden of HSV-2 infection, the cause of most cases of genital
herpes in Nigeria, varies from region to region; and so are the associated
factors. This infection is known to be responsible for several negative pregnancy
outcomes. There is currently no documented data on sexual behavioral factors
associated with the occurrence of HSV-2 infection or seroprevalence among
pregnant women in Nigeria. This study aimed at identifying the sexual behavioral
correlates of HSV-2 seroprevalence among pregnant women in Benin City, Nigeria.
METHODOLOGY: The cross-sectional study design was adopted and the study took
place between November 2011 and June 2012. Four hundred and ten consenting ante
natal clinic patients in two major tertiary hospitals in Benin City were
consecutively and prospectively included. Data sources were represented by
questionnaires, the patient's case records and laboratory investigations. Each
patient's serum was analyzed for HSV-2 antibody detection. Data analysis was
performed using SPSS version 16. RESULTS: Four hundred and ten patients were
enrolled with average age 30.6 years. Seroprevalence of HSV-2 antibody was 47.3%.
Sexual behavioral factors that were significantly associated with HSV-2
seroprevalence included early exposure to sexual intercourse, number of sex
partners, involvement in polygamous marriages, involvement of husband in extra
marital affairs and hormonal contraceptive use. CONCLUSION: The prevalence of HSV
2 among pregnant women in Benin City is high. Public health campaigns aimed at:
delaying onset of sexual activity; encouraging monogamous relationships; and
emphasizing that hormonal contraceptives do not protect from STI's, are
recommended.
PMID- 25116667
TI - Prevalence of "anti-HBc alone" among Syrian blood donors.
AB - INTRODUCTION: We aimed to evaluate the prevalence of "anti-HBc alone" among
Syrian blood donors, highlighting the possibility of representing occult HBV
infection. METHODOLOGY: Sera of 3,896 healthy blood donors were tested for both
HBsAg and anti-HBc. HBsAg-negative, anti-HBc-positive samples were further tested
for the antibodies to HBsAg (anti-HBs), and "anti-HBc alone" sera were tested for
HBV DNA. RESULTS: Of 3,830 HBsAg-negative donors, 63 were "anti-HBc alone"
donors, five of whom were HBV DNA positive. CONCLUSIONS: Greater consideration
should be given to the "anti-HBc alone" serological profile in blood screening,
premarital testing, organ transplantation tests, and other HBV transmission
related procedures in Syria.
PMID- 25116668
TI - Diagnosis and molecular typing of rabies virus in samples stored in inadequate
conditions.
AB - INTRODUCTION: The exposure of nervous tissue samples to high temperatures affects
the sensitivity of rabies virus diagnostic tests, causing degradation of the
viral structure. This study evaluated reverse transcriptase polymerase chain
reaction (RT-PCR) for the diagnosis and molecular characterization of brain
tissue samples in an advanced state of decomposition and poorly conserved viral
isolates by comparing it with routine diagnostic tests. METHODOLOGY: A panel of
three canine brain samples exposed to controlled decomposition for 7, 15, 30, and
120 days were evaluated using fluorescence antibody test (FAT), mouse inoculation
test (MIT), and RT-PCR. In addition, 14 isolates of rabies variants, representing
the largest circulation in Argentina, preserved in inadequate cooling for six to
eight years were analyzed. Molecular typing of strains was performed using a 159
nucleotide region corresponding to the nucleoprotein gene. RESULTS: The three
samples analyzed were positive by RT-PCR at all the decomposition times
evaluated, in contrast to results observed with FAT and MIT, which rapidly became
negative. In addition, 100% of the inadequately preserved samples were
characterized molecularly. The limit of detection of RT-PCR was 0.5 MICDL50/0.03
mL. CONCLUSION: RT-PCR can be useful for rabies diagnosis and typing of
putrefying samples or rabies isolates stored in inadequate conditions.
PMID- 25116669
TI - Seroprevalence and risk factors for toxoplasmosis in large ruminants in northern
Punjab, Pakistan.
AB - INTRODUCTION: Toxoplasmosis is a widespread zoonosis that causes significant
economic losses due to abortions and other developmental disabilities in
livestock animals. The objectives of the current study were to determine the
prevalence and associated risk factors of Toxoplasma gondii infection in cattle
and buffaloes in northern parts of Punjab, Pakistan, where no such work
previously existed. METHODOLOGY: Serum samples obtained from 400 cattle and 422
buffaloes present on different private and government-owned farms were tested for
anti-Toxoplasma IgG and anti-Toxoplasma IgM antibodies by using enzyme linked
immunosorbent assay (ELISA). Additional data, including water sources, hygienic
status at the farm, management practices, size of the herd, and presence of cats
in the vicinity of the farm were obtained using a questionnaire in surveys and
interviews. RESULTS: The overall prevalence of infection was 19.75% (79/400) in
cattle and 15.16% (64/422) in buffaloes. IgG antibodies were found in 75 (18.75%)
cattle and 58 (13.74%) buffaloes, while IgM antibodies were found in 9 (2.25%)
cattle and 10 (2.37%) buffaloes. Seroprevalence was significantly higher in
females and older animals of both species. Seroprevalence was found to be
associated with poor hygienic conditions, extensive management practices, and
presence of cats in the surrounding areas. No difference of seroprevalence was
observed with respect to different breeds, location, water source, and herd size.
CONCLUSION: The present study found that T. gondii is prevalent in large
ruminants in northern Punjab, and may have important implications for the
livestock industry and public health.
PMID- 25116670
TI - Prevalence of Trypanosoma cruzi infection in blood donors in El Salvador between
2001 and 2011.
AB - INTRODUCTION: El Salvador is regarded as a highly endemic country for Chagas
disease, as evidenced by the relatively high estimated positive serology rate for
Trypanosoma cruzi among blood donors. This study aimed to identify the factors
contributing to this high rate by analyzing changes in T. cruzi seroprevalence.
METHODOLOGY: Secondary data were collected from 31 blood banks operated by the
Ministry of Health, the Red Cross, the Institute of Salvadoran Social Security,
and the Military Hospital. The data were analyzed to determine the number of
cases of T. cruzi seropositivity, and the average prevalence of seropositivity by
province. Simple linear regression was performed to identify trends in T. cruzi
seropositivity. RESULTS: Analysis of the 885,187 blood samples collected between
2001 and 2011 revealed 21,693 cases of transfusion-related infections, with a
significant reduction of T. cruzi seropositivity from 3.7% in 2001 to 1.7% in
2011, reflecting a 54% decrease over the course of a decade (R(2) = 89.6%, p >
0.001). T. cruzi seroprevalence decreased in San Salvador, Santa Ana, Sonsonate,
and Cuscatlan. In contrast, seroprevalence remained high with no decrease in
Ahuachapan and San Vicente, and consistently low in the remainder of the country.
CONCLUSIONS: Although the national prevalence of T. cruzi among blood donors has
decreased, it remains high in the provinces of Ahuachapan and San Vicente.
Strengthening vector control activities and developing an approach for the
systematic follow-up of prospective blood donors with positive serology for T.
cruzi are required, especially in areas with high seropositivity.
PMID- 25116671
TI - Molecular typing and in vitro antifungal susceptibility of Cryptococcus spp from
patients in Midwest Brazil.
AB - INTRODUCTION: Cryptococcosis is a systemic fungal infection that affects humans
and animals, mainly due to Cryptococcus neoformans and Cryptococcus gattii.
Following the epidemic of acquired immunodeficiency syndrome (AIDS), fungal
infections by C. neoformans have become more common among immunocompromised
patients. Cryptococcus gattii has primarily been isolated as a primary pathogen
in healthy hosts and occurs endemically in northern and northeastern Brazil. We
to perform genotypic characterization and determine the in vitro susceptibility
profile to antifungal drugs of the Cryptococcus species complex isolated from HIV
positive and HIV-negative patients attended at university hospitals in Cuiaba,
MT, in the Midwestern region of Brazil. METHODOLOGY: Micromorphological features,
chemotyping with canavanine-glycine-bromothymol blue (CGB) agar and genotyping by
URA5-RFLP were used to identify the species. The antifungal drugs tested were
amphotericin B, fluconazole, flucytosine, itraconazole and voriconazole. Minimum
inhibitory concentrations (MICs) were determined according to the CLSI
methodology M27-A3. RESULTS: Analysis of samples yelded C. neoformans AFLP1/VNI
(17/27, 63.0%) and C. gattii AFLP6/VGII (10/27, 37.0%). The MICs ranges for the
antifungal drugs were: amphotericin B (0.5-1 mg/L), fluconazole (1-16 mg/L),
flucytosine (1-16 mg/L), itraconazole (0.25-0.12 mg/L) and voriconazole (0.06-0.5
mg/L). Isolates of C. neoformans AFLP1/VNI were predominant in patients with
HIV/AIDS, and C. gattii VGII in HIV-negative patients. The genotypes identified
were susceptible to the antifungal drugs tested. CONCLUSION: It is worth
emphasizing that AFLP6/VGII is a predominant genotype affecting HIV-negative
individuals in Cuiaba. These findings serve as a guide concerning the molecular
epidemiology of C. neoformans and C. gattii in the State of Mato Grosso.
PMID- 25116672
TI - Detection of the novel IMP-38 among carbapenemase-producing Enterobacteriaceae in
a university hospital, China.
AB - INTRODUCTION: This study set out to investigate the molecular epidemiology of
carbapenemase-producing Enterobacteriaceae isolates collected from Xiang Ya
Hospital, Hunan, China. METHODOLOGY: The carbapenemase genes from
Enterobacteriaceae isolates were determined by PCR and sequencing. Relatedness of
Klebsiella pneumoniae isolates was evaluated by pulsed-field gel electrophoresis.
RESULTS: Twenty-four out of 738 non-repetitive Enterobacteriaceae isolates
harbored carbapenemase genes including IMP-38, a novel IMP-type metallo-enzyme.
Nine IMP-38-producing isolates were shown to originate from the same clone and
caused a small outbreak in the neonatal ward. CONCLUSIONS: IMP-38, a novel IMP
type metallo-enzyme, was one of the predominant types of carbapenemase in the
clinical carbapenem-resistant Enterobacteriaceae isolates in our hospital.
PMID- 25116673
TI - Risk factors for carbapenem-resistant Acinetobacter baumanii blood stream
infections in a neonatal intensive care unit, Delhi, India.
AB - INTRODUCTION: Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is
being increasingly observed and is associated with significant morbidity and
mortality in newborns. In this study, we determined the epidemiology, risk
factors, and outcomes of blood stream infection (BSI) caused by CRAB in neonates.
METHODOLOGY: The clinical charts of neonates who developed Acinetobacter
baumannii BSI in the period between 1 January 2010 and 31 December 2012 were
reviewed. RESULTS: During the study period, 65 neonates developed Acinetobacter
baumannii BSI; 33 were CRAB at an incidence of 0.50 case per 1,000 patient-days.
Compared with carbapenem-sensitive Acinetobacter baumannii (CSAB), patients with
CRAB BSI had significantly higher prior antimicrobial use, longer duration of
ventilation, and late isolation of organisms. Feeding with expressed breast milk
was protective. All isolates of Acinetobacter baumenii were sensitive to colistin
and tigecycline. The all-cause mortality rates were 27.3% in CRAB and 9.4% in
CSAB BSI, respectively (p = 0.074). CONCLUSIONS: Neonatal BSI caused by CRAB was
not common but caused high mortality. Feeding with breast milk was protective.
Lack of effective antibiotics was the major challenge in treating these patients.
PMID- 25116674
TI - Lipolytic activity of Staphylococcus aureus from human wounds, animals, foods,
and food-contact surfaces in Brazil.
AB - INTRODUCTION: S. aureus is of great importance to public health due to its
pathogenicity. This study aimed to evaluate lipase production by S. aureus
isolates from different sources. METHODOLOGY: Lipolytic activity was determined
using Tween-Calcium agar (48 hours; 35 degrees C). RESULTS: Eighty-six percent of
the isolates from human wounds were positive for lipase production. The
frequencies of isolates positive for lipase production were 33.3% from cow
udders, 15.4% from the nasal cavities of cattle, 82.9% from ricotta cheeses, and
100% and 91.7% from meat- and vegetable-contact surfaces, respectively.
CONCLUSION: The production of lipase varied among the isolates according to their
source.
PMID- 25116675
TI - Transportation of sputum samples in cetylpyridinium chloride for drug resistance
studies from remote areas of Odisha, India.
AB - INTRODUCTION: Antimicrobial susceptibility testing of Mycobacterium tuberculosis
is required for successful treatment of patients, mainly in retreatment cases
which necessitate isolation of mycobacteria from sputum samples within 24-48
hours. In situations where transportation of sputum is required, the use of
cetylpyridinium chloride (CPC) effectively sustains the viability of mycobacteria
up to two weeks. METHODOLOGY: Sputum samples were collected from pulmonary TB
patients attending designated microscopy centres (DMC), stored in CPC solution
and transported to a culture drug susceptibility testing laboratory using
overnight bus transport facilities. For culture, the sputum specimens were
processed and inoculated in Lowenstein- Jensen (LJ) medium. Growth on LJ was
identified by colony morphology, growth rate and biochemical tests, and transit
time was calculated as the time taken from the date of sample collection to the
inoculation date. RESULTS: Out of the 816 sputum samples collected in CPC, 691
(84.7%) yielded M. tuberculosis, 97 (11.9%) yielded no growth, 21(2.6%) grew
contaminants and 7 (0.8%) were nontuberculous mycobacteria. CPC containing sputum
samples processed within two weeks showed 88.6% culture positivity, while
positivity was significantly affected beyond two weeks. CONCLUSIONS: CPC is
cheap, easy to use, inhibits the growth of other organisms and can effectively be
used to transport sputum specimens within two weeks from hard to reach areas to
central locations without compromising culture positivity. Bus transport services
can also help in reducing delay and the cost of transportation from remote areas.
PMID- 25116676
TI - Antiretroviral drug resistance and HIV-1 subtypes among treatment-naive prisoners
in Kelantan, Malaysia.
AB - INTRODUCTION: The widespread use of highly active antiretroviral therapy (HAART)
and continuous reports of HIV-1 strains developing resistance to these drugs is
rather alarming, as transmission of resistant viruses to newly infected persons
is possible. This study aimed to determine HIV-1 subtypes and the prevalence of
primary mutations associated with antiretroviral (ARV) resistance among treatment
naive prisoners on the east coast of Malaysia. METHODOLOGY: Viral RNA was
extracted from plasma samples of 21 treatment-naive prisoners. Protease (PR) and
reverse transcriptase (RT) regions were amplified and sequenced. Stanford HIV
database algorithms were used for interpretation of resistance, and phylogenetic
analysis was performed for subtype assignment. RESULTS: In the PR gene, no
antiviral resistance-associated mutation was detected. For RT-associated
mutations, K103N was the most prevalent in sequenced samples (14.3%). Genetic
subtyping on the pol gene revealed that the majority of the prisoners were
infected with subtype CRF33_01B (52.4%). CONCLUSION: Continuous surveillance of
newly infected individuals is required to help strategize the best antiviral
treatment for these patients.
PMID- 25116677
TI - Higher levels of hepatitis C virus RNA found in blood donors co-infected with HIV
as compared to HCV mono-infected donors.
AB - INTRODUCTION: Hepatitis C virus (HCV) infection and human immunodeficiency virus
(HIV) infections are public health problems in sub-Saharan countries such as the
Republic of Congo. HIV infection could impact the characteristics of HCV
infection in co-infected people. We investigated HCV-HIV co-infection among blood
donors in Congo. METHODOLOGY: Ninety-nine HIV-positive and/or HCV-seropositive
blood donors were selected during screening and subsequently tested for
aminotransferases and HCV RNA. RESULTS: A total of 29 donors were found positive
for HCV RNA (HCV-infected individuals), including 19/60 (31.66%) HIV donors (co
infected) and 10/39 (25.64%) non-HIV donors (mono-infected). Most of the co
infected donors (17/19) displayed a high viral load (> 5 log). The median HCV RNA
level was at least 2 logs higher in co-infected people. The levels of alanine
aminotransferase (ALT) were also slightly higher in co-infected donors than in
HCV mono-infected donors. CONCLUSION: This study reports HCV-HIV co-infection
among blood donors in Congo and shows that HCV viral load is higher in HIV
donors.
PMID- 25116678
TI - Hantavirus infection mimicking leptospirosis: how long are we going to rely on
clinical suspicion?
AB - Hantavirus infections and leptospirosis can have similar clinical and
epidemiological features. We present here a case study of a young farmer with
fever during the post-flood leptospirosis outbreak in Anuradhapura, Sri Lanka, in
2011. He presented with a classical clinical picture of leptospirosis and was
managed and notified as a case of leptospirosis. Retrospective analysis of a
stored serum sample confirmed acute hantavirus infection. Diagnosis of newly
identified or emerging infectious diseases such as hantavirus infection is
challenging due to the lack of diagnostic facilities in developing countries.
This case highlights the need for improving diagnostic facilities, educating
medical staff, and conducting population-based prospective studies on hantavirus
infections in Sri Lanka.
PMID- 25116679
TI - Dengue encephalopathy - still an enigma?
AB - Dengue encephalopathy or dengue hemorrhagic fever (DHF) with neurological
involvement was once considered to be one of the rarer presentations of this
infectious agent. In recent years, many such clinical cases have been reported,
though they still remain isolated. We hereby report a case of confirmed dengue
fever with features of encephalopathy with previously unreported cranial magnetic
resonance imaging findings suggestive of extensive involvement of the bilateral
cerebellar region, brainstem, and thalami along with peculiar rim enhancement but
normal cerebrospinal fluid analysis.
PMID- 25116680
TI - Parainfluenza virus 4 presenting with pericardial effusion in an immunocompetent
child.
PMID- 25116681
TI - Disease prevention: saving lives or reducing health care costs?
AB - BACKGROUND: Disease prevention has been claimed to reduce health care costs.
However, preventing lethal diseases increases life expectancy and, thereby,
indirectly increases the demand for health care. Previous studies have argued
that on balance preventing diseases that reduce longevity increases health care
costs while preventing non-fatal diseases could lead to health care savings. The
objective of this research is to investigate if disease prevention could result
in both increased longevity and lower lifetime health care costs. METHODS:
Mortality rates for Netherlands in 2009 were used to construct cause-deleted life
tables. Data originating from the Dutch Costs of Illness study was incorporated
in order to estimate lifetime health care costs in the absence of selected
disease categories. We took into account that for most diseases health care
expenditures are concentrated in the last year of life. RESULTS: Elimination of
diseases that reduce life expectancy considerably increase lifetime health care
costs. Exemplary are neoplasms that, when eliminated would increase both life
expectancy and lifetime health care spending with roughly 5% for men and women.
Costs savings are incurred when prevention has only a small effect on longevity
such as in the case of mental and behavioural disorders. Diseases of the
circulatory system stand out as their elimination would increase life expectancy
while reducing health care spending. CONCLUSION: The stronger the negative impact
of a disease on longevity, the higher health care costs would be after
elimination. Successful treatment of fatal diseases leaves less room for
longevity gains due to effective prevention but more room for health care
savings.
PMID- 25116682
TI - Evaluation of in vitro cytotoxicity and genotoxicity of copper-zinc alloy
nanoparticles in human lung epithelial cells.
AB - In the present study, in vitro cytotoxic and genotoxic effect of copper-zinc
alloy nanoparticles (Cu-Zn ANPs) on human lung epithelial cells (BEAS-2B) were
investigated. XTT test and clonogenic assay were used to determine cytotoxic
effects. Cell death mode and intracellular reactive oxygen species formations
were analyzed using M30, M65 and ROS Elisa assays. Genotoxic effects were
evaluated using micronucleus, comet and gamma-H2AX foci assays. Cu-Zn ANPs were
characterized by transmission electron microscopy (TEM), dynamic light scattering
(DLS) and zeta potential measurements. Characterization of Cu-Zn ANPs showed an
average size of 200nm and zeta potential of -22mV. TEM analyses further revealed
the intracellular localization of Cu-Zn ANPs in cytoplasm within 24h. Analysis of
micronucleus, comet and gamma-H2AX foci counts showed that exposure to Cu-Zn ANPs
significantly induced chromosomal damage as well as single and double stranded
DNA damage in BEAS-2B cells. Our results further indicated that exposure to Cu-Zn
ANPs significantly induced intracellular ROS formation. Evaluation of M30:M65
ratios suggested that cell death was predominantly due to necrosis.
PMID- 25116683
TI - Theoretical study of the transpore velocity control of single-stranded DNA.
AB - The electrokinetic transport dynamics of deoxyribonucleic acid (DNA) molecules
have recently attracted significant attention in various fields of research. Our
group is interested in the detailed examination of the behavior of DNA when
confined in micro/nanofluidic channels. In the present study, the translocation
mechanism of a DNA-like polymer chain in a nanofluidic channel was investigated
using Langevin dynamics simulations. A coarse-grained bead-spring model was
developed to simulate the dynamics of a long polymer chain passing through a
rectangular cross-section nanopore embedded in a nanochannel, under the influence
of a nonuniform electric field. Varying the cross-sectional area of the nanopore
was found to allow optimization of the translocation process through modification
of the electric field in the flow channel, since a drastic drop in the electric
potential at the nanopore was induced by changing the cross-section. Furthermore,
the configuration of the polymer chain in the nanopore was observed to determine
its translocation velocity. The competition between the strength of the electric
field and confinement in the small pore produces various transport mechanisms and
the results of this study thus represent a means of optimizing the design of
nanofluidic devices for single molecule detection.
PMID- 25116684
TI - Rapamycin-Induced apoptosis in HGF-stimulated lens epithelial cells by AKT/mTOR,
ERK and JAK2/STAT3 pathways.
AB - Hepatocyte growth factor (HGF) induced the proliferation of lens epithelial cells
(LECs) and may be a major cause of posterior capsule opacification (PCO), which
is the most frequent postoperative complication of cataract surgery. To date,
several agents that can block LECs proliferation have been studied, but none have
been used in clinic. Recently, accumulating evidence has suggested rapamycin, the
inhibitor of mTOR (mammalian target of Rapamycin), was associated with the
induction of apoptosis in LECs. The purpose of our study was to investigate the
potential effects of rapamycin on HGF-induced LECs and the underlying mechanisms
by which rapamycin exerted its actions. Using cell proliferation, cell viability
and flow cytometric apoptosis assays, we found that rapamycin potently not only
suppressed proliferation but also induced the apoptosis of LECs in a dose
dependent manner under HGF administration. Further investigation of the
underlying mechanism using siRNA transfection revealed that rapamycin could
promote apoptosis of LECs via inhibiting HGF-induced phosphorylation of AKT/mTOR,
ERK and JAK2/STAT3 signaling molecules. Moreover, the forced expression of AKT,
ERK and STAT3 could induce a significant suppression of apoptosis in these cells
after treatment of rapamycin. Together, these findings suggested that rapamycin
induced apoptosis in HGF-stimulated LECs is accompanied by inhibition of
AKT/mTOR, ERK and JAK2/STAT3 pathways, which supports its use to inhibit PCO in
preclinical studies and provides theoretical foundation for future possible
practice.
PMID- 25116686
TI - Effect of beta-glucan supplementation on acute postprandial changes in fatty acid
profile of lymph and serum in pigs.
AB - Triglycerides are absorbed by the lymphatic system and have various functions in
the body. It has been shown that some types of beta-glucans have a positive
effect on the systemic concentrations of cholesterol and lipid, presumably
through interference with the absorption of lipid and/or reabsorption of bile
acids. In the current study we investigated the acute effects of ingesting 2 g of
beta-glucan concentrates derived from barley beta-(1->3)(1->4)-D-glucan or yeast
beta-(1->3)(1->6)-D-glucan on fatty acid content and composition in lymph and
serum of 10 female pigs (initial weight 34.7+/-1.1 kg) fitted with a permanent
catheter in the jejunal lymphatic trunk in a cross-over design. Lymph was
collected continuously for 8 h followed by a spot sample taken 24 h after. A
significant effect of time after feeding was observed for all fatty acids in
serum and for 18:0, 18:2omega6 and 18:3omega3 in lymph, but a significant effect
of beta-glucan was only observed for 14:0 (p=0.049) and 22:6omega3 (p=0.048) in
lymph and 18:0 (p=0.019) in serum. While the concentration of dietary fatty acids
increased postprandially in lymph, the concentration of arachidonic and
docahexanoic acid tended to decrease. Furthermore, there was a drop in
concentration of all fatty acid in serum 1 h after the meal.
PMID- 25116687
TI - Heterosis in early maize ear inflorescence development: a genome-wide
transcription analysis for two maize inbred lines and their hybrid.
AB - Heterosis, or hybrid vigor, contributes to superior agronomic performance of
hybrids compared to their inbred parents. Despite its importance, little is known
about the genetic and molecular basis of heterosis. Early maize ear
inflorescences formation affects grain yield, and are thus an excellent model for
molecular mechanisms involved in heterosis. To determine the parental
contributions and their regulation during maize ear-development-genesis, we
analyzed genome-wide digital gene expression profiles in two maize elite inbred
lines (B73 and Mo17) and their F1 hybrid using deep sequencing technology. Our
analysis revealed 17,128 genes expressed in these three genotypes and 22,789
genes expressed collectively in the present study. Approximately 38% of the genes
were differentially expressed in early maize ear inflorescences from heterotic
cross, including many transcription factor genes and some presence/absence
variations (PAVs) genes, and exhibited multiple modes of gene action. These
different genes showing differential expression patterns were mainly enriched in
five cellular component categories (organelle, cell, cell part, organelle part
and macromolecular complex), five molecular function categories (structural
molecule activity, binding, transporter activity, nucleic acid binding
transcription factor activity and catalytic activity), and eight biological
process categories (cellular process, metabolic process, biological regulation,
regulation of biological process, establishment of localization, cellular
component organization or biogenesis, response to stimulus and localization).
Additionally, a significant number of genes were expressed in only one inbred
line or absent in both inbred lines. Comparison of the differences of modes of
gene action between previous studies and the present study revealed only a small
number of different genes had the same modes of gene action in both maize
seedlings and ear inflorescences. This might be an indication that in different
tissues or developmental stages, different global expression patterns prevail,
which might nevertheless be related to heterosis. Our results support the
hypotheses that multiple molecular mechanisms (dominance and overdominance modes)
contribute to heterosis.
PMID- 25116688
TI - Epigenetic determinants of CYP1A1 induction by the aryl hydrocarbon receptor
agonist 3,3',4,4',5-pentachlorobiphenyl (PCB 126).
AB - Many enzymes involved in xenobiotic metabolism, including cytochrome P450 (CYP)
1A1, are regulated by the aryl hydrocarbon receptor (AhR). 3,3',4,4',5-Penta
chlorobiphenyl (PCB 126) is a potent ligand for AhR and can thus induce the
expression of CYP1A1. Interestingly, we observed that human carcinoma cell lines
derived from different types of epithelial cells displayed divergent degrees of
CYP1A1 induction after exposure to PCB 126. Since epigenetic mechanisms are known
to be involved in cell type-specific gene expression, we sought to assess the
epigenetic determinants of CYP1A1 induction in these carcinoma cell lines. In
contrast to HepG2 hepatocarcinoma cells, HeLa cervical carcinoma cells showed
significantly lower levels of CYP1A1 mRNA expression following PCB 126 exposure.
Our results show that the two cell lines maintained differences in the chromatin
architecture along the CYP1A1 promoter region. Furthermore, treatment with the
epigenetic modifiers, trichostatin A (TSA) and 5-aza-2'-deoxycytidine (5-Aza-dC),
significantly increased the expression of CYP1A1 after PCB 126 treatment in HeLa
cells. However, we did not observe apparent differences in methylation levels or
specific location of CpG DNA methylation between the two cell lines in the
analyzed CYP1A1 promoter region. Taken together, our findings suggest that the
differences in CYP1A1 expression between HepG2 and HeLa cells are due to
differences in the chromatin architecture of the CYP1A1 promoter and thus
establish a role of epigenetic regulation in cell-specific CYP1A1 expression.
PMID- 25116689
TI - Localization of MLH3 at the centrosomes.
AB - Mutations in human DNA mismatch repair (MMR) genes are commonly associated with
hereditary nonpolyposis colorectal cancer (HNPCC). MLH1 protein heterodimerizes
with PMS2, PMS1, and MLH3 to form MutLalpha, MutLbeta, and MutLgamma,
respectively. We reported recently stable expression of GFP-linked MLH3 in human
cell lines. Monitoring these cell lines during the cell cycle using live cell
imaging combined with confocal microscopy, we detected accumulation of MLH3 at
the centrosomes. Fluorescence recovery after photobleaching (FRAP) revealed high
mobility and fast exchange rates at the centrosomes as it has been reported for
other DNA repair proteins. MLH3 may have a role in combination with other repair
proteins in the control of centrosome numbers.
PMID- 25116690
TI - Effects of psychotherapy on DNA strand break accumulation originating from
traumatic stress.
AB - BACKGROUND: Previous research reveals an association between traumatic stress and
an increased risk for numerous diseases, including cancer. At the molecular
level, stress may increase carcinogenesis via increased DNA damage and impaired
DNA repair mechanisms. We assessed DNA breakage in peripheral blood mononuclear
cells from individuals with post-traumatic stress disorder (PTSD) and measured
the cellular capacity to repair single-strand breaks after exposure to ionizing X
radiation. We also investigated the effect of psychotherapy on both DNA breakage
and DNA repair. METHODS: In a first study we investigated DNA breakage and repair
in 34 individuals with PTSD and 31 controls. Controls were subdivided into 11
trauma-exposed subjects and 20 individuals without trauma exposure. In a second
study, we analysed the effect of psychotherapy (Narrative Exposure Therapy) on
DNA breakage and repair. Thirty-eight individuals with PTSD were randomly
assigned to either a treatment or a waitlist control condition. Follow-up was
performed 4 months and 1 year after therapy. RESULTS: In study 1 we found higher
levels of basal DNA breakage in individuals with PTSD and trauma-exposed subjects
than in controls, indicating that traumatic stress is associated with DNA
breakage. However, single-strand break repair was unimpaired in individuals with
PTSD. In study 2, we found that psychotherapy reversed not only PTSD symptoms,
but also DNA strand break accumulation. CONCLUSION: Our results show - for the
first time in vivo - an association between traumatic stress and DNA breakage;
they also demonstrate changes at the molecular level, i.e., the integrity of DNA,
after psychotherapeutic interventions.
PMID- 25116691
TI - Understanding and reducing the experimental variability of in vitro plasma
protein binding measurements.
AB - The experimental measurement of plasma protein binding is a useful in vitro
Absorption Distribution Metabolism and Excretion(ADME) assay currently conducted
in both screening and definitive early development candidate modes. The fraction
unbound is utilized to calculate important pharmacokinetic (PK) parameters such
as unbound clearance and unbound volume of distribution in animals that can be
used to make human PK and dose predictions and estimate clinically relevant drug
drug interaction potential. Although these types of assays have been executed for
decades, a rigorous statistical analysis of sources of variability has not been
conducted because of the tedious nature of the manual experiment. Automated
conduct of the incubations using a 96-well equilibrium dialysis device as well as
high-throughput liquid chromatography-mass spectrometry quantitation has now made
this level of rigor accessible and useful. Sources of variability were assessed
including well position, day-to-day, and site-to-site reproducibility. Optimal pH
conditions were determined using a design of experiments method interrogating
buffer strength, CO2 % and device preparation conditions. Variability was
minimized by implementing an in-well control that is concurrently analyzed with
new chemical entity analytes. Data acceptance criteria have been set for both the
in-well control and the range of analyte variability, with a sliding scale tied
to analyte-binding characteristics. (c) 2014 Wiley Periodicals, Inc. and the
American Pharmacists Association J Pharm Sci 103:3302-3309, 2014.
PMID- 25116692
TI - Analysis of STAT1 expression and biological activity reveals interferon-tau
dependent STAT1-regulated SOCS genes in the bovine endometrium.
AB - Signal transducer and activator of transcription (STAT) proteins are critical for
the regulation of numerous biological processes. In cattle, microarray analyses
identified STAT1 as a differentially expressed gene in the endometrium during the
peri-implantation period. To gain new insights about STAT1 during the oestrous
cycle and early pregnancy, we investigated STAT1 transcript and protein
expression, as well as its biological activity in bovine tissue and cells of
endometrial origin. Pregnancy increased STAT1 expression on Day 16, and protein
and phosphorylation levels on Day 20. In cyclic and pregnant females, STAT1 was
located in endometrial cells but not in the luminal epithelium at Day 20 of
pregnancy. The expression of STAT1 during the oestrous cycle was not affected by
progesterone supplementation. In vivo and in vitro, interferon-tau (IFNT)
stimulated STAT1 mRNA expression, protein tyrosine phosphorylation and nuclear
translocation. Using chromatin immunoprecipitation in IFNT-stimulated endometrial
cells, we demonstrated an increase of STAT1 binding on interferon regulatory
factor 1 (IRF1), cytokine-inducible SH2-containing protein (CISH), suppressor of
cytokine signaling 1 and 3 (SOCS1, SOCS3) gene promoters consistent with the
induction of their transcripts. Our data provide novel molecular insights into
the biological functions of STAT1 in the various cells composing the endometrium
during maternal pregnancy recognition and implantation.
PMID- 25116695
TI - Trajectory study of energy transfer and unimolecular dissociation of highly
excited allyl with argon.
AB - The influence of rotational excitation on energy transfer in single collisions of
allyl with argon and on allyl dissociation is investigated. About 90,000
classical scattering simulations are performed in order to determine collision
induced changes in internal energy and in allyl rotational angular momentum.
Dissociation is studied by means of about 50,000 additional trajectories evolved
for the isolated allyl under three different conditions: allyl with no angular
momentum (J = 0); allyl with the same microcanonically sampled initial conditions
used for the collisions (J*); allyl evolving from the corresponding exit
conditions after the collision. The potential energy surface is the sum of an
intramolecular potential and an interaction one, and it has already been used in
a previous work on allyl-argon scattering (Conte, R.; Houston, P. L.; Bowman, J.
M. J. Phys. Chem. A 2013, 117, 14028-14041). Energy transfer data show that
increased initial rotation favors, on average, increased relaxation of the
excited molecule. The availability of a high-level intramolecular potential
energy surface permits us to study the dependence of energy transfer on the type
of starting allyl isomer. A turning point analysis is presented, and highly
efficient collisions are detected. Collision-induced variations in the allyl
rotational angular momentum may be quite large and are found to be distributed
according to three regimes. The roles of rotational angular momentum, collision,
and type of isomer on allyl unimolecular dissociation are considered by looking
at dissociations times, kinetic energies of the fragments, and branching ratios.
Generally, rotational angular momentum has a strong influence on the dissociation
dynamics, while the single collision and the type of starting isomer are less
influential.
PMID- 25116694
TI - Costs associated with adverse events in patients with metastatic renal cell
carcinoma.
AB - OBJECTIVE: To estimate adverse event (AE) costs in patients receiving targeted
therapies for the first line treatment of metastatic renal cell carcinoma (mRCC).
METHODS: Retrospective study based on healthcare claims data for patients with
mRCC, aged >=18 years, receiving first-line treatment with targeted therapies.
AEs of interest comprised of abdominal pain, back pain, diarrhea, dyspnea,
extremity pain, fatigue/asthenia, hand-foot syndrome, hypertension, lymphopenia,
nausea/vomiting, neutropenia, proteinuria, and thrombocytopenia. Healthcare
encounters for AEs were based on ICD-9-CM diagnosis/procedure codes on healthcare
claims. AE costs were examined over a 30-day period, beginning with the date of
first mention of AE, and were estimated based on the difference in total costs
between patients with and without events. Drug costs of targeted agents were
excluded from the analysis. Multivariate generalized linear models with a log
link function and gamma response probability distribution were utilized to
control for differences in baseline characteristics between patients with and
without evidence of AEs. RESULTS: A total of 533 patients were included in this
analysis: 418 patients with AE and 115 patients without AE. Baseline
characteristics were generally similar between patients in the two groups. The
GLM-based estimate of incremental 30-day post-event costs among patients with
evidence of any adverse events was $9807 (95% CI = $4386-$22,947). For all types
of adverse events examined, the estimated difference in costs between evented and
non-evented patients was positive; the 95% CI did not include zero for all of the
adverse events considered, except hypertension and proteinurea. Study limitations
include errors of commission/omission, especially as they may affect case-finding
methods that rely on ICD-9-CM diagnosis and procedure codes, as was the case in
the current study. CONCLUSION: Costs associated with AEs of first-line targeted
therapies are substantial in patients with mRCC. Efforts to prevent and/or better
manage these events may reduce overall healthcare costs.
PMID- 25116693
TI - Treatment experience, burden and unmet needs (TRIBUNE) in MS study: results from
Turkey.
AB - OBJECTIVE: To estimate the economic burden of multiple sclerosis (MS) in Turkey,
including the relapses and disease severity, and to evaluate the quality-of-life
of MS patients. METHODS: The Treatment Experience, Burden and Unmet Needs
(TRIBUNE) study was a multi-national, cross-sectional, retrospective, burden-of
illness survey. Total costs were calculated using unit costs derived from price
lists or published literature, where relevant, and inflated to 2011 TL prices.
RESULTS: A total of 295 MS patients (74% females) were included in the analysis.
The population had a mean age of 36 years; 73% had the relapsing-remitting form.
Mean Expanded Disability Status Scale (EDSS) score was 2.2. Twenty-two per cent
of the MS patients required hospitalization in the past year and spent an average
of 29.2 days/year in hospital. These values were 43% and 5.6 days for the
outpatients, respectively. Total cost per patient/year was 18,700 TL (Turkish
Lira). Total costs for patients with mild, moderate, and severe disability were
15,418 TL, 26,002 TL, and 44,208 TL per patient/year, respectively. The mean
EuroQol 5D scores in the same groups were 0.73, 0.52, and 0.05, respectively.
CONCLUSIONS: Multiple sclerosis imposes a significant economic burden on patients
and society in Turkey.
PMID- 25116685
TI - Antibacterial surface treatment for orthopaedic implants.
AB - It is expected that the projected increased usage of implantable devices in
medicine will result in a natural rise in the number of infections related to
these cases. Some patients are unable to autonomously prevent formation of
biofilm on implant surfaces. Suppression of the local peri-implant immune
response is an important contributory factor. Substantial avascular scar tissue
encountered during revision joint replacement surgery places these cases at an
especially high risk of periprosthetic joint infection. A critical pathogenic
event in the process of biofilm formation is bacterial adhesion. Prevention of
biomaterial-associated infections should be concurrently focused on at least two
targets: inhibition of biofilm formation and minimizing local immune response
suppression. Current knowledge of antimicrobial surface treatments suitable for
prevention of prosthetic joint infection is reviewed. Several surface treatment
modalities have been proposed. Minimizing bacterial adhesion, biofilm formation
inhibition, and bactericidal approaches are discussed. The ultimate anti
infective surface should be "smart" and responsive to even the lowest bacterial
load. While research in this field is promising, there appears to be a great
discrepancy between proposed and clinically implemented strategies, and there is
urgent need for translational science focusing on this topic.
PMID- 25116696
TI - Play behavior of the golden-headed lion tamarin in Brazilian cocoa agroforests.
AB - During play, primates may become more vulnerable to predation. Our goal was to
examine the potential role of predation risk on the play behavior of 3 groups of
golden-headed lion tamarin, Leontopithecus chrysomelas, in shaded cocoa
agroforest (cabruca) of Southern Bahia, Brazil. We identified the preferred (and
safer) locations on vertical strata during playtime and investigated if frequency
and duration of play differed according to group size. All groups preferred to
play on the lower levels of vertical strata, which may be perceived as either a
safer environment or as a more suitable location for play due to the vegetation
structure. The smallest group played less than the others, while the largest
group played more and for longer periods. Our data suggest that predation risk
can influence where play takes place as well as its frequency and length.
PMID- 25116697
TI - Copper-catalyzed aerobic oxidative cleavage of C-C bonds in epoxides leading to
aryl ketones.
AB - A novel copper-catalyzed aerobic synthesis of ketones from epoxides via cleavage
of C-C single bonds has been discovered. This reaction constitutes a new
transformation from epoxides into ketones.
PMID- 25116700
TI - Dynamic contrast-enhanced magnetic resonance imaging biomarkers in head and neck
cancer: potential to guide treatment? A systematic review.
AB - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) generates
microvascular parameters from the tracer kinetic analysis of a series of MRI
images obtained in under 15 min. DCE-MRI parameters are associated with tumour
hypoxia, which is well-established as a cause of treatment failure in head and
neck squamous cell carcinoma (HNSCC). A systematic review was conducted of
prospective DCE-MRI parameter studies in HNSCC in the English language
literature. Exclusion criteria were case reports and retrospective series. Six
DCE-MRI marker studies in HNSCC met the inclusion criteria. Four studies
contained 21-74 patients and two studies recruited 13 and 14 patients. In studies
measuring the transfer coefficient (K(trans)), higher overall K(trans) or lower
skewness of K(trans) were predictive of a good outcome following chemoradiation.
DCE-MRI parameters have the potential to guide treatment in HNSCC. Progress in
the field requires standardisation of methods, data sharing and large multi
centre collaborative validation studies.
PMID- 25116698
TI - Spectroscopic characterization and reactivity studies of a mononuclear nonheme
Mn(III)-hydroperoxo complex.
AB - We report the first example of a mononuclear nonheme manganese(III)-hydroperoxo
complex derived from protonation of an isolated manganese(III)-peroxo complex
bearing an N-tetramethylated cyclam (TMC) ligand, [Mn(III)(TMC)(OOH)](2+). The
Mn(III)-hydroperoxo intermediate is characterized with various spectroscopic
methods as well as with density functional theory (DFT) calculations, showing the
binding of a hydroperoxide ligand in an end-on fashion. The Mn(III)-hydroperoxo
species is a competent oxidant in oxygen atom transfer (OAT) reactions, such as
the oxidation of sulfides. The electrophilic character of the Mn(III)-hydroperoxo
complex is demonstrated unambiguously in the sulfoxidation of para-substituted
thioanisoles.
PMID- 25116702
TI - Highly porous NiCo2O4 Nanoflakes and nanobelts as anode materials for lithium-ion
batteries with excellent rate capability.
AB - Highly porous NiCo2O4 nanoflakes and nanobelts were synthesized by using a
hydrothermal technique, followed by calcination of the NiCo2O4 precursors. The as
synthesized materials were analyzed by scanning electron microscopy, X-ray
diffraction, transmission electron microscopy, and Brunauer-Emmett-Teller
methods. The NiCo2O4 nanoflakes and nanobelts were applied as anode materials for
lithium-ion batteries. Owing to the unique porous structural features, the
NiCo2O4 nanoflakes and nanobelts exhibited high specific capacities of 1033 and
1056 mA h g(-1), respectively, and good cycling stability and rate capability.
These exceptional electrochemical performances could be ascribed to the
remarkable structural feature with a high surface area and void spaces within the
surface of nanoflakes and nanobelts, which provide large contact areas between
electrolyte and active materials for electrolyte diffusion and cushion the volume
variation during the lithium-ion insertion/extraction process.
PMID- 25116701
TI - Pressure-induced magnetic crossover driven by hydrogen bonding in CuF2(H2O)2(3
chloropyridine).
AB - Hydrogen bonding plays a foundational role in the life, earth, and chemical
sciences, with its richness and strength depending on the situation. In molecular
materials, these interactions determine assembly mechanisms, control
superconductivity, and even permit magnetic exchange. In spite of its long
standing importance, exquisite control of hydrogen bonding in molecule-based
magnets has only been realized in limited form and remains as one of the major
challenges. Here, we report the discovery that pressure can tune the
dimensionality of hydrogen bonding networks in CuF2(H2O)2(3-chloropyridine) to
induce magnetic switching. Specifically, we reveal how the development of O
H...Cl exchange pathways under compression combined with an enhanced ab-plane
hydrogen bonding network yields a three dimensional superexchange web between
copper centers that triggers a reversible magnetic crossover. Similar pressure-
and strain-driven crossover mechanisms involving coordinated motion of hydrogen
bond networks may play out in other quantum magnets.
PMID- 25116703
TI - Synthesis of 1,3,5,7-tetrakis(4-cyanatophenyl)adamantane and its microporous
polycyanurate network for adsorption of organic vapors, hydrogen and carbon
dioxide.
AB - This report presents the synthesis of a tetraphenyladamantane-based microporous
polycyanurate network with a BET surface area of 843 m(2) g(-1) and a pore size
of 7.8 A. It uptakes 98.0 wt% benzene (298 K, P/P0 = 0.9), 1.49 wt% H2 (77 K/1
bar) and 12.8 wt% CO2 (273 K/1 bar) with CO2/N2 selectivity of up to 112.
PMID- 25116704
TI - Adipocyte versus pituitary leptin in the regulation of pituitary hormones:
somatotropes develop normally in the absence of circulating leptin.
AB - Leptin is a cytokine produced by white fat cells, skeletal muscle, the placenta,
and the pituitary gland among other tissues. Best known for its role in
regulating appetite and energy expenditure, leptin is produced largely by and in
proportion to white fat cells. Leptin is also important to the maintenance and
function of the GH cells of the pituitary. This was shown when the deletion of
leptin receptors on somatotropes caused decreased numbers of GH cells, decreased
circulating GH, and adult-onset obesity. To determine the source of leptin most
vital to GH cells and other pituitary cell types, we compared two different
leptin knockout models with Cre-lox technology. The global Lep-null model is like
the ob/ob mouse, whereby only the entire exon 3 is deleted. The selective
adipocyte-Lep-null model lacks adipocyte leptin but retains pituitary leptin,
allowing us to investigate the pituitary as a potential source of circulating
leptin. Male and female mice lacking adipocyte leptin (Adipocyte-lep-null) did
not produce any detectable circulating leptin and were infertile, suggesting that
the pituitary does not contribute to serum levels. In the presence of only
pituitary leptin, however, these same mutants were able to maintain somatotrope
numbers and GH mRNA levels. Serum GH trended low, but values were not
significant. However, hypothalamic GHRH mRNA was significantly reduced in these
animals. Other serum hormone and pituitary mRNA differences were observed, some
of which varied from previous results reported in ob/ob animals. Whereas
pituitary leptin is capable of maintaining somatotrope numbers and GH mRNA
production, the decreased hypothalamic GHRH mRNA and low (but not significant)
serum GH levels indicate an important role for adipocyte leptin in the regulation
of GH secretion in the mouse. Thus, normal GH secretion may require the
coordinated actions of both adipocyte and pituitary leptin.
PMID- 25116705
TI - A mollusk retinoic acid receptor (RAR) ortholog sheds light on the evolution of
ligand binding.
AB - Nuclear receptors are transcription factors that regulate networks of target
genes in response to small molecules. There is a strong bias in our knowledge of
these receptors because they were mainly characterized in classical model
organisms, mostly vertebrates. Therefore, the evolutionary origins of specific
ligand-receptor couples still remain elusive. Here we present the identification
and characterization of a retinoic acid receptor (RAR) from the mollusk Nucella
lapillus (NlRAR). We show that this receptor specifically binds to DNA response
elements organized in direct repeats as a heterodimer with retinoid X receptor.
Surprisingly, we also find that NlRAR does not bind all-trans retinoic acid or
any other retinoid we tested. Furthermore, NlRAR is unable to activate the
transcription of reporter genes in response to stimulation by retinoids and to
recruit coactivators in the presence of these compounds. Three-dimensional
modeling of the ligand-binding domain of NlRAR reveals an overall structure that
is similar to vertebrate RARs. However, in the ligand-binding pocket (LBP) of the
mollusk receptor, the alteration of several residues interacting with the ligand
has apparently led to an overall decrease in the strength of the interaction with
the ligand. Accordingly, mutations of NlRAR at key positions within the LBP
generate receptors that are responsive to retinoids. Altogether our data suggest
that, in mollusks, RAR has lost its affinity for all-trans retinoic acid,
highlighting the evolutionary plasticity of its LBP. When put in an evolutionary
context, our results reveal new structural and functional features of nuclear
receptors validated by millions of years of evolution that were impossible to
reveal in model organisms.
PMID- 25116707
TI - Decidualization induces a secretome switch in perivascular niche cells of the
human endometrium.
AB - The endometrial perivascular microenvironment is rich in mesenchymal stem-like
cells that express type 1 integral membrane protein Sushi domain containing 2
(SUSD2) but the role of these cells in the decidual transformation of this tissue
in pregnancy is unknown. We used an antibody directed against SUSD2 (W5C5) to
isolate perivascular (W5C5(+)) and nonperivascular (W5C5(-)) fibroblasts from mid
luteal biopsies. We show that SUSD2 expression, and hence the ratio of
W5C5(+):W5C5(-) cells, changes in culture depending on cell-cell contact and
activation of the Notch signaling pathway. RNA sequencing revealed that cultures
derived from W5C5(+) progenitor cells remain phenotypically distinct by the
enrichment of novel and established endometrial perivascular signature genes. In
an undifferentiated state, W5C5(+)-derived cells produced lower levels of various
chemokines and inflammatory modulators when compared with their W5C5(-)
counterparts. This divergence in secretomes was switched and became more
pronounced upon decidualization, which transformed perivascular W5C5(+) cells
into the dominant source of a range of chemokines and cytokines, including
leukemia inhibitory factor and chemokine (C-C motif) ligand 7. Our findings
suggest that the decidual response is spatially organized at the embryo-maternal
interface with differentiating perivascular cells establishing distinct cytokine
and chemokine profiles that could potentially direct trophoblast toward maternal
vessels and govern local immune responses in pregnancy.
PMID- 25116708
TI - Insulin action on GABA neurons is a critical regulator of energy balance but not
fertility in mice.
AB - Insulin signaling in the brain plays an important role in the central regulation
of energy homeostasis and fertility, such that mice exhibiting brain-specific
deletion of insulin receptors (InsRs) display a diet-sensitive obesogenic
phenotype and hypothalamic hypogonadism. However, the specific neurons mediating
insulin's central effects on fertility remain largely unidentified. The
neurotransmitters gamma-aminobutyric acid (GABA) and glutamate are important
modulators of fertility and energy homeostasis and are widely distributed in the
hypothalamus. We therefore investigated whether insulin signaling via GABAergic
or glutamatergic neurons plays an important role in the metabolic regulation of
fertility. We used the Cre-loxP system to generate mice with a selective
inactivation of the Insr gene from GABAergic (Vgat(+)) or glutamatergic
(Vglut2(+)) cells by crossing Insr-flox mice with Vgat-Cre or Vglut2-Cre mice,
respectively. Multiple reproductive and metabolic parameters were then compared
between male and female Insr-flox/Vgat-Cre(+) (VgatIRKO), Insr-flox/Vglut2-Cre(+)
(VglutIRKO), and Insr-flox/Cre-negative control (CON) mice. Female VgatIRKO mice
exhibited a significant increase in adult body weight, abdominal fat mass, and
fasting plasma insulin and leptin concentrations, but normal fasting glucose
concentration and glucose tolerance compared with CON mice. Surprisingly,
VgatIRKO and VglutIRKO mice exhibited normal reproductive maturation and function
compared with CONs. No differences in the age of puberty onset, estrous
cyclicity, or fertility were observed between VgatIRKO, VglutIRKO, and CON mice.
However, male VgatIRKO mice exhibited significantly augmented LH concentration
and a trend toward reduced seminal vesicle weight compared with CON mice, which
may be indicative of primary hypogonadism. Our results therefore demonstrate that
insulin signaling via GABAergic and glutamatergic cells is not required for
fertility in mice, but show that GABAergic neurons encompass circuitry through
which insulin acts to modulate energy homeostasis.
PMID- 25116706
TI - GLP-1 receptor stimulation of the lateral parabrachial nucleus reduces food
intake: neuroanatomical, electrophysiological, and behavioral evidence.
AB - The parabrachial nucleus (PBN) is a key nucleus for the regulation of feeding
behavior. Inhibitory inputs from the hypothalamus to the PBN play a crucial role
in the normal maintenance of feeding behavior, because their loss leads to
starvation. Viscerosensory stimuli result in neuronal activation of the PBN.
However, the origin and neurochemical identity of the excitatory neuronal input
to the PBN remain largely unexplored. Here, we hypothesize that hindbrain
glucagon-like peptide 1 (GLP-1) neurons provide excitatory inputs to the PBN,
activation of which may lead to a reduction in feeding behavior. Our data,
obtained from mice expressing the yellow fluorescent protein in GLP-1-producing
neurons, revealed that hindbrain GLP-1-producing neurons project to the lateral
PBN (lPBN). Stimulation of lPBN GLP-1 receptors (GLP-1Rs) reduced the intake of
chow and palatable food and decreased body weight in rats. It also activated lPBN
neurons, reflected by an increase in the number of c-Fos-positive cells in this
region. Further support for an excitatory role of GLP-1 in the PBN is provided by
electrophysiological studies showing a remarkable increase in firing of lPBN
neurons after Exendin-4 application. We show that within the PBN, GLP-1R
activation increased gene expression of 2 energy balance regulating peptides,
calcitonin gene-related peptide (CGRP) and IL-6. Moreover, nearly 70% of the lPBN
GLP-1 fibers innervated lPBN CGRP neurons. Direct intra-lPBN CGRP application
resulted in anorexia. Collectively, our molecular, anatomical,
electrophysiological, pharmacological, and behavioral data provide evidence for a
functional role of the GLP-1R for feeding control in the PBN.
PMID- 25116709
TI - The American Board of Clinical Neuropsychology and American Academy of Clinical
Neuropsychology: updated milestones 2005-2014.
PMID- 25116710
TI - Brain alterations in paedophilia: a critical review.
AB - Psychosocial and biological factors have been implicated in paedophilia, such as
alterations in brain structure and function. The purpose of this paper is to
review the expanding body of literature on this topic including brain abnormality
case reports, as well as structural and functional neuroimaging studies. Case
studies of men who have committed sexual offences against children implicate
frontal and temporal abnormalities that may be associated with impaired impulse
inhibition. Structural neuroimaging investigations show volume reductions in
paedophilic men. Although the findings have been heterogeneous, smaller amygdala
volume has been replicated repeatedly. Functional neuroimaging investigations
demonstrate an overlap between paedophiles and teleiophiles during sexual arousal
processing. While it is controversial among studies regarding group differences,
reliable discrimination between paedophilic and teleiophilic men may be achieved
using functional activation patterns. Nevertheless, the heterogeneous findings
published so far suggest further research is necessary to disentangle the
neurobiological mechanisms of paedophilic preference. A number of methodological
confounds have been identified, which may account for the inconsistent results
that could prove to be beneficial for future investigations.
PMID- 25116711
TI - The role of P2X7 receptor in infectious inflammatory diseases and the influence
of ectonucleotidases.
AB - The purinergic receptor P2X ligand-gated ion channel 7 (P2X7) is ubiquitously
expressed in almost all tissues and organs of the body with the highest
distribution in the immune cells of monocyte-macrophage origin. Classically, P2X7
receptor is involved in apoptotic cell death, and it is well known that
extracellular ATP ligation to this purinergic receptor serves as an important
secondary stimulus, which is also considered as danger signal for the interleukin
(IL)-1beta cleavage and secretion from pro-inflammatory cells. More recently,
however, there has been substantial evidence of additional roles for the P2X7
receptor, both in innate immune response and as an adaptive link, including T
cell activation in a chronic state of inflammation. Also, compelling evidences
have revealed an important role for ectonucleotidases as ATP-consuming enzymes in
the control and fine-tuning of P2X7 function by regulating the time,
concentration, and availability of ATP during infection-driven inflammation. This
review focuses on the current evidences for P2X7 receptor involvement in the
initial stages of inflammation, as well as for its role in acute and chronic
stages of infection. Here, we also highlight the role of ectonucleotidase family
in the control of P2X7 function, including the initial and resolution phases of
inflammation.
PMID- 25116712
TI - Proton pump inhibitors and risk for Clostridium difficile associated diarrhea.
AB - Increased incidence of Clostridium difficile infection (CDI) among in-patients is
associated with significant increased mortality, morbidity, and stay in the
hospitals. This has occurred despite heightened awareness of the risks of broad
spectrum antibiotics, overall reduction in antibiotic use and increased focus on
hospital hygiene. So though the main risk factor for CDI is use of broad-spectrum
antibiotics, the use of proton pump inhibitors (PPIs) as a novel potential
contributor has been implicated, because of their ability to substantially reduce
gastric acid secretion which is an important host defense mechanism in
suppressing the ingested C. difficile or its spores. Antibiotic disruption of the
normal intestinal flora and reduced gastric acidity have been suggested as the
risk factors for C. difficile-associated diarrhea (CDAD). Based on such
assumptions the use of PPIs may be associated with an increased risk of CDAD.
While a definite association between PPI use and CDAD has not yet been confirmed,
the possibility and such an association however cannot be ruled out at present.
Thus among the identified risk factors, the use of PPI is important, previously
unrecognized and modifiable risk factors whose use should be carefully evaluated
among hospital in-patients receiving antibiotics, especially in those with a
diagnosis of C. difficile diarrhea.
PMID- 25116713
TI - Systematic review of the surgery-first approach in orthognathic surgery.
AB - The surgery-first approach in orthognathic surgery has recently created a broader
interest in completely eliminating time-consuming preoperative orthodontic
treatment. Available evidence on the surgery-first approach should be appraised
to support its use in orthognathic surgery. A MEDLINE search using the keywords
"surgery first" and "orthognathic surgery" was conducted to select studies using
the surgery-first approach. We also manually searched the reference list of the
selected keywords to include articles not selected by the MEDLINE search. The
search identified 18 articles related to the surgery-first approach. There was no
randomized controlled clinical trial. Four papers were excluded as the content
was only personal opinion or basic scientific research. Three studies were
retrospective cohort studies in nature. The other 11 studies were case reports.
For skeletal Class III surgical correction, the final long-term outcomes for
maxillofacial and dental relationship were not significantly different between
the surgery-first approach and the orthodontics-first approach in transverse
(e.g., intercanine or intermolar width) dimension, vertical (e.g., anterior open
bite, lower anterior facial height) dimension, and sagittal (e.g., anterior
posterior position of pogonion and lower incisors) dimension. Total treatment
duration was substantially shorter in cases of surgery-first approach use. In
conclusion, most published studies related to the surgery-first approach were
mainly on orthognathic correction of skeletal Class III malocclusion. Both the
surgery-first approach and orthodontics-first approach had similar long-term
outcomes in dentofacial relationship. However, the surgery-first approach had
shorter treatment time.
PMID- 25116714
TI - PPARgamma ligand ciglitazone inhibits TNFalpha-induced ICAM-1 in human airway
smooth muscle cells.
AB - BACKGROUND: Modification of human airway smooth muscle (ASM) function by
proinflammatory cytokines has been regarded as a potential mechanism underlying
bronchial hyperresponsiveness in asthma. Human ASM cells express intercellular
adhesion molecule (ICAM)-1 in response to cytokines. Synthetic ligands for
peroxisome proliferator-activated receptor (PPAR)gamma reportedly possess anti
inflammatory and immunomodulatory properties. In this study, we examined whether
ciglitazone, a synthetic PPARgamma ligand, can modulate the basal and tumor
necrosis factor (TNF)alpha-induced ICAM1 gene expression in human ASM cells.
METHODS: Human ASM cells were treated with TNFalpha. ICAM-1 expression was
assessed by flow cytometry and reverse transcriptase-polymerase chain reaction
(RT-PCR) analysis. PPARgamma activity was inhibited by target-specific small
interfering (si) RNA targeting PPARgamma and GW9662, a PPARgamma antagonist.
Activity of nuclear factor (NF)-kappaB was assessed by using immunoblot analysis,
immune-confocal images, and electrophoretic mobility shift assay (EMSA). RESULTS:
By flow cytometry, ciglitazone alone had no effect on ICAM-1 expression in ASM
cells, but inhibited ICAM-1 expression in response to TNFalpha (10 ng/ml) in a
dose-dependent manner (1-10 MUM). It also inhibited TNFalpha-induced ICAM1 gene
expression by RT-PCR analysis. Knockdown of PPARgamma gene by target-specific
siRNA targeting PPARgamma enhanced ICAM-1 expression and the inhibitory effect of
ciglitazone on TNFalpha-induced ICAM-1 expression was reversed by PPARgamma siRNA
and GW9662. SN-50 (10 MUg/ml), an inhibitor for nuclear translocation of NF
kappaB, inhibited TNFalpha-induced ICAM-1 expression. Ciglitazone did not prevent
TNFalpha-induced degradation of the cytosolic inhibitor of NF-kappaB (IkappaB),
but inhibited the nuclear translocation of p65 induced by TNFalpha and suppressed
the NF-kappaB/DNA binding activity. CONCLUSION: These findings suggest that
ciglitazone inhibits TNFalpha-induced ICAM1 gene expression in human ASM cells
through the ligand-dependent PPARgamma activation and NF-kappaB-dependent
pathway.
PMID- 25116715
TI - Thromboprophylaxis after minimally invasive total knee arthroplasty: a comparison
of rivaroxaban and enoxaparin.
AB - BACKGROUND: Total knee arthroplasty (TKA) carries a substantial rate of venous
thromboembolism (VTE). The blood-saving of effect of tranexamic acid (TEA) in TKA
using enoxaparin for thromboprophylaxis has been well known. However, the routine
use of chemoprophylaxis in TKA remains controversial because of postoperative
bleeding complications. Therefore, the purpose of this study was to
retrospectively compare the incidence of VTE, and postoperative blood loss and
wound-related complications in minimally invasive (MIS)-TKA patients who received
rivaroxaban or enoxaparin prophylaxis. METHODS: A total of 113 patients who
underwent primary unilateral MIS-TKA between 2009 and 2012 were studied. Of
these, 61 patients (study group) received rivaroxaban prophylaxis between 2011
and 2012 and a control group of 52 patients received enoxaparin prophylaxis
between 2009 and 2010. All patients received one intraoperative injection of TEA
(10 mg/kg). We compared the changes in hemoglobin (Hb) level, postoperative
drainage amount, total blood loss, transfusion rate, and incidence of
postoperative wound complications and VTE between the two groups. RESULTS: No
differences in postoperative Hb levels, blood drainage amount, total blood loss,
and transfusion rate were observed between the two groups. No deep-vein
thrombosis of the leg or pulmonary embolism was noted in both groups. There were
no major wound complications including hematoma and infection requiring surgical
intervention for open irrigation or debridement. CONCLUSIONS: Our retrospective
study demonstrated a low rate of VTE in MIS-TKA patients who received rivaroxaban
or enoxaparin when TEA was used for bleeding prophylaxis. No increased
perioperative bleeding or postoperative wound-related complications were observed
in the rivaroxaban group compared with the enoxaparin group.
PMID- 25116716
TI - Effects of neuromuscular electrical stimulation on arterial hemodynamic
properties and body composition in paretic upper extremities of patients with
subacute stroke.
AB - BACKGROUND: Neuromuscular electric stimulation (NMES) induces repeated muscular
contraction, possibly promoting the perfusion/oxygenation of the regional
tissues. It remains unclear how NMES influences vascular hemodynamic property and
segmental fluid distribution/composition in paretic extremities of hemiplegic
patients. METHODS: Eleven hemiplegic patients aged 62.6 +/- 12.5 years in the
subacute stage of stroke received NMES for paretic wrist extensor and flexor
muscles 30 min daily, 5 days per week for 4 weeks. The non-paretic upper
extremities (NPUE) that did not receive NMES served as control. Distribution of
fluid to intra/extracellular milieu and arterial hemodynamic properties were
determined by using the multi-frequency bioelectrical impedance and pulse wave
analysis, respectively. RESULTS: Compared with NPUE without NMES, paretic upper
extremity (PUE) with NMES revealed a significantly less decrease in arterial
blood flow, impedance quotient, slope quotient, and less increase in crest width
and crest time of arterial pulse wave. NMES for 4 weeks increased body cell mass
in PUE. Furthermore, NPUE without NMES reduced intracellular water, whereas PUE
with NMES retarded loss of intracellular water after stroke. CONCLUSION: NMES
therapy increases body cell mass, attenuates reduction of intracellular water,
and alleviates arterial hemodynamic disturbance in PUE in subacute stroke.
However, stroke-related physical deconditioning may negatively regulate body
composition and impair hemodynamic function in NPUE.
PMID- 25116717
TI - Extended shelf life of random donor platelets stored for 7 days in platelet
additive solution at different temperatures.
AB - BACKGROUND: Platelets are routinely stored in plasma for 5 days at an average
temperature of 22 degrees C. In the present study, the shelf life of random donor
platelets was extended by storing for 7 days with and without additive solution
at temperatures of 22 degrees C, 18 degrees C, and 16 degrees C. METHODS: Random
donor platelets were stored in 100% plasma and 20%/80% platelet additive
solution. The data were compared using paired "t"- test. The confidence limit was
kept at 95%, hence a "p" < 0.05 was considered to be statistically significant.
RESULTS: Out of total 150 samples, 148 samples were analyzed and 2 were discarded
due to the bacterial contamination on day 7 at 22 degrees C without platelet
additive solution. A significant difference in platelet count, platelet factor 3
(PF 3), glucose, lactate dehydrogenase (LDH), and platelet aggregation was
observed on day 7 (p < 0.001) at 16 degrees C in without platelet additive
solution. In platelet additive solution, the mean values of platelet count,
platelet distribution width (PDW), LDH, and pH showed no significant difference
on day 7 at 22 degrees C, 18 degrees C, and 16 degrees C. Only significant
differences were observed in the levels of mean platelet volume (MPV), PF 3,
glucose, and platelet aggregation on day 7 (p < 0.001) at 16 degrees C of the
storage period. CONCLUSION: Random donor platelets functions are better
maintained in platelet additive solution as compared to plasma at a lower
temperature of 18 degrees C but not at 16 degrees C, on the 7 th day.
PMID- 25116719
TI - Effect of environmental enrichment exposure on neuronal morphology of
streptozotocin-induced diabetic and stressed rat hippocampus.
AB - BACKGROUND: Environmental enrichment (EE) exposure is known to influence the
structural changes in the neuronal network of hippocampus. In the present study,
we evaluated the effects of EE exposure on the streptozotocin (STZ)-induced
diabetic and stressed rat hippocampus. METHODS: Male albino rats of Wistar strain
(4-5 weeks old) were grouped into normal control (NC), vehicle control (VC),
diabetes (DI), diabetes + stress (DI + S), diabetes + EE (DI + E), and diabetes +
stress + EE (DI + S + E) groups (n = 8 in each group). Rats were exposed to
stress and EE after inducing diabetes with STZ (40 mg/kg). Rats were sacrificed
on Day 30 and brain sections were processed for cresyl violet staining to
quantify the number of surviving neurons in the CA1, CA3, and dentate hilus (DH)
regions of hippocampus. RESULTS: A significant (p < 0.001) decrease in the number
of survived neurons was noticed in DI (CA1, 34.06 +/- 3.2; CA3, 36.1 +/- 3.62;
DH, 9.83 +/- 2.02) as well as DI + S (CA1, 14.03 +/- 3.12; CA3, 20.27 +/- 4.09;
DH, 6.4 +/- 1.21) group rats compared to NC rats (CA1, 53.64 +/- 2.96; CA3, 62.1
+/- 3.34; DH, 21.11 +/- 1.03). A significant (p < 0.001) increase in the number
of survived neurons was observed in DI + E (CA1, 42.3 +/- 3.66; CA3, 46.73 +/-
4.74; DH, 17.03 +/- 2.19) and DI + S + E (CA1, 29.69 +/- 4.47; CA3, 36.73 +/-
3.89; DH, 12.23 +/- 2.36) group rats compared to DI and DI + S groups,
respectively. CONCLUSIONS: EE exposure significantly reduced the amount of
neuronal damage caused by complications of diabetes and stress to the neurons of
hippocampus.
PMID- 25116718
TI - Anti-adhesive effect of hyaluronate in a rabbit laminectomy model.
AB - BACKGROUND: Postlaminectomy dural adhesion is a common cause of recurrent
symptoms. Hyaluronic acid-based gel has been reported to reduce the incidence of
postoperative adhesion in the peritoneal cavity; however, its effect on
preventing postoperative scar formation at laminectomy sites is not yet known.
The purpose of this study was to evaluate the anti-adhesive effect of hyaluronic
acid-based gelatin after laminectomy, using a rabbit model. METHODS: Twelve adult
New Zealand rabbits underwent two-level lumbar laminectomy, and were randomly
assigned to one of two groups of six rabbits each. The treatment group received
hyaluronic acid-based gelatin treatment and the control group was untreated.
Rabbits were sacrificed 8 weeks after treatment. Peel-off testing and
histological analysis were performed to assess the tenacity and the extent of
adhesion formation. RESULTS: No significant difference was observed in the
neurologic performance between the two groups. The tenacity in the treatment
group was significantly reduced compared to that of the control group (3.17 +/-
0.75 vs. 4.33 +/- 0.52, respectively; p = 0.016). Histological analysis showed
significantly less scar tissue formation in the treatment group, with a larger
subarachnoid space and greater distance between the dura and scar tissues. The
amount of fibroblast cells also was significantly smaller in the treatment group
than in the control group (3078 +/- 313.68 vs. 3742 +/- 455.65, respectively; p =
0.042). CONCLUSIONS: No serious adverse events were reported, and no difference
was found in the incidence of complications between the treatment and control
groups. The findings suggested that hyaluronic acid-based gelatin may be
effective for preventing postlaminectomy dural adhesion in rabbits.
PMID- 25116720
TI - Fetal magnetic resonance imaging of normal spinal cord: evaluating cord
visualization and conus medullaris position by T2-weighted sequences.
AB - BACKGROUND: Prenatal magnetic resonance (MR) imaging demonstration of the normal
spinal cord and the conus medullaris location has not been well studied. We
compared balanced fast field echo (bFFE) with single-shot turbo spin-echo (SSh
TSE) MR sequences for visualizing the normal spinal cord and position of conus
medullaris in fetuses. METHODS: This retrospective study was approved by the
Institutional Review Board of Chang Gung Medical Foundation. We reviewed the MR
images of 141 fetuses aged between 16 and 39 gestational weeks, to determine the
position of the conus and visualize the spinal cord by using a signal intensity
ratio of cerebral spinal fluid (CSF) to the spinal cord. RESULTS: Of the 75
subjects having normal spinal cord and being examined by both bFFE and SSh-TSE
studies, the signal intensity ratio of CSF/cord was greater on bFFE images (2.18
+/- 0.53) than that on SSh-TSE images (1.21 +/- 0.13) (p < 0.05). The conus level
identified in the 50 subjects, in whom the lumbosacral spine was appropriately
imaged, was located from L1 to L5 levels. The ascendance of the conus correlated
moderately with gestational age. CONCLUSIONS: With greater signal contrast ratio
of CSF to spinal cord, bFFE sequence, when compared with SSh-TSE sequence,
provides better visualization of normal spinal cord. The fetal conus medullaris
ascends from L5 to L1 levels as the gestational age increases.
PMID- 25116721
TI - Co-infusion of autologous adipose tissue derived neuronal differentiated
mesenchymal stem cells and bone marrow derived hematopoietic stem cells, a viable
therapy for post-traumatic brachial plexus injury: a case report.
AB - Stem cell therapy is emerging as a viable approach in regenerative medicine. A 31
year-old male with brachial plexus injury had complete sensory-motor loss since
16 years with right pseudo-meningocele at C5-D1 levels and extra-spinal extension
up to C7-D1, with avulsion on magnetic resonance imaging and irreversible damage.
We generated adipose tissue derived neuronal differentiated mesenchymal stem
cells (N-AD-MSC) and bone marrow derived hematopoietic stem cells (HSC-BM).
Neuronal stem cells expressed beta-3 tubulin and glial fibrillary acid protein
which was confirmed on immunofluorescence. On day 14, 2.8 ml stem cell inoculum
was infused under local anesthesia in right brachial plexus sheath by brachial
block technique under ultrasonography guidance with a 1.5-inch-long 23 gauge
needle. Nucleated cell count was 2 * 10 4 /MUl, CD34+ was 0.06%, and CD45-/90+
and CD45-/73+ were 41.63% and 20.36%, respectively. No untoward effects were
noted. He has sustained recovery with re-innervation over a follow-up of 4 years
documented on electromyography-nerve conduction velocity study.
PMID- 25116722
TI - Conformational and H-bonding preferences for facile racemate crystallization of
ribose.
AB - Recalcitrant crystallization and syrup formation are frequent features of natural
sugars. This is the case of D-ribose, yielding low-quality crystals of mixed
alpha- and beta-pyranose anomers. However, large crystals of DL-ribose can be
grown easily. The crystal structures of stable D-ribose forms I and II as well as
DL-form II have been analyzed in terms of their compatibility with the molecular
aggregation. The comparison of the potential energy of all conformers and their
OH...O hydrogen-bonding patterns is consistent with the preferential racemate
crystallization in terms of departures from the optimized isolated ribose
molecule and its directional interactions. This analysis is aimed at
rationalizing the interplay between the molecular structure and spontaneous
crystallization of chiral compounds.
PMID- 25116723
TI - Nickelalactones with an allyl subunit - the effect of penta-coordination on
structures and stability.
AB - A series of allyl modified nickelalactone derivatives of the general formula
[(L)nNi{CH2C(CH3)C(CH3)CH2COO}] was synthesized via ligand exchange reactions in
order to investigate the influence of the neutral ligand L on the structure and
stability of these complexes. While the square planar 1,8
diazabicyclo[5,4,0]undec-7-ene ligated derivative 1 is stable in the solid state
and in solution at ambient temperature, the use of the chelating ligands 6
diphenylphosphino-1,8-diazabicyclo[5.4.0]undec-7-ene, 1,1
bis(dicyclohexylphosphino)methane and 1,2-bis(dicyclohexylphosphino)ethane (dcpe)
led to square pyramidal derivatives 2, 4, and 5 with a novel ligand arrangement.
In solution, these derivatives are fluxional and show increasing tendencies in
the order 2 < 4 < 5 to decouple the nickelalactone moiety to 2,3
dimethylbutadiene (dmbd), CO2 and zero-valent nickel complexes. During the
investigation of 5, the tetrahedral complex [(dcpe)2Ni] (6) and the trigonal
planar derivative [(dcpe)Ni(dmbd)] (7) were observed as predominant decomposition
products. In the case of the application of 1,1-bis(diphenylphosphino)methane as
a neutral ligand, a dinuclear nickelalactone species [(MU
dppm)(Ni{CH2C(CH3)C(CH3)CH2COO})2] (3) was isolated in which the two nickel atoms
realize different coordination geometries (SP-4 and SPY-5) in the solid state.
The complexes were characterized by NMR techniques, single crystal X-ray
diffraction measurements and infrared spectroscopy.
PMID- 25116724
TI - Autologous haematopoietic stem cell transplantation reduces abnormalities in the
expression of immune genes in multiple sclerosis.
AB - Autologous haematopoietic stem-cell transplantation (AHSCT) has been experimented
as a treatment in patients affected by severe forms of multiple sclerosis (MS)
who failed to respond to standard immunotherapy. The rationale of AHSCT is to
'reboot' the immune system and reconstitute a new adaptive immunity. The aim of
our study was to identify, through a robust and unbiased transcriptomic analysis,
any changes of gene expression in T-cells potentially underlying the treatment
effect in patients who underwent non-myeloablative AHSCT for treatment of MS. We
evaluated by microarray DNA-chip technology the gene expression of peripheral
CD4+ and CD8+ T-cell subsets sorted from patients with MS patients before AHSCT,
at 6 months, 1 year and 2 years after AHSCT and from healthy control subjects.
Hierarchical clustering analysis revealed that reconstituted CD8+ T-cells of MS
patients at 2 years post-transplantation, aggregated together with healthy
controls, suggesting a normalization of gene expression in CD8+ cells post
therapy. When we compared the gene expression in MS patients before and after
therapy, we detected a large number of differentially expressed genes (DEG) in
both CD8+ and CD4+ T-cell subsets at all time points after transplantation. We
catalogued the biological function of DEG and we selected 27 genes known to be
involved in immune function for accurate quantification of gene expression by
real-time PCR. The analysis confirmed and extended with quantitative data, a
number of significant changes in both the CD4+ and CD8+ T-cells subsets from MS
post-transplant. Notably, CD8+ T-cells revealed more extensive changes in the
expression of genes involved in effector immune responses.
PMID- 25116725
TI - Recovery of flavonoids from orange press liquor by an integrated membrane
process.
AB - Orange press liquor is a by-product generated by the citrus processing industry
containing huge amounts of natural phenolic compounds with recognized antioxidant
activity. In this work, an integrated membrane process for the recovery of
flavonoids from orange press liquors was investigated on a laboratory scale. The
liquor was previously clarified by ultrafiltration (UF) in selected operating
conditions by using hollow fiber polysulfone membranes. Then, the clarified
liquor with a total soluble solids (TSS) content of 10 g.100 g-1 was pre
concentrated by nanofiltration (NF) up to 32 g TSS 100 g-1 by using a
polyethersulfone spiral-wound membrane. A final concentration step, up to 47 g
TSS 100 g-1, was performed by using an osmotic distillation (OD) apparatus
equipped with polypropylene hollow fiber membranes. Suspended solids were
completely removed in the UF step producing a clarified liquor containing most
part of the flavonoids of the original press liquor due to the low rejection of
the UF membrane towards these compounds. Flavanones and anthocyanins were highly
rejected by the NF membrane, producing a permeate stream with a TSS content of
4.5 g.100 g-1. An increasing of both the flavanones and anthocyanins
concentration was observed in the NF retentate by increasing the volume reduction
factor (VRF). The final concentration of flavonoids by OD produced a concentrated
solution of interest for nutraceutical and pharmaceutical applications.
PMID- 25116727
TI - Optimising retention through multiple study opportunities over days: The benefit
of an expanding schedule of repetitions.
AB - Few studies have investigated how scheduling repeated studies of the same
material over several days influences its subsequent retention. The study-phase
retrieval hypothesis predicts that, under these circumstances, expanding
intervals between repetitions will promote the greatest likelihood that the
participant will be reminded of previous occurrences of the item, thus leading to
a benefit for subsequent recall. In the present article, participants studied
vocabulary pairs that were repeated according to one of three schedules. In the
expanding schedule, pairs were presented on days 1, 2 and 13; in the uniform
schedule, on days 1, 7 and 13; and in the contracting schedule, on days 1, 12 and
13. Cued-recall was assessed after a retention interval (RI) of 2, 6 or 13 days.
Consistent with predictions, the expanding schedule generally led to better
performance than the other schedules. However, further analyses suggested that
the benefit of an expanding schedule may be greater when the RI is longer.
PMID- 25116728
TI - Retraction: common occurrence of ceftriaxone-resistant, methicillin-sensitive
Staphylococcus aureus at a Community Teaching Hospital.
PMID- 25116731
TI - New cyanopyridone based luminescent liquid crystalline materials: synthesis and
characterization.
AB - A new series of 4-(3,4-bis(akyloxy)phenyl)-6-(4-((1-(4-cyano- or 4-nitro-benzyl)
1H-1,2,3-triazol-4-yl)methoxy)phenyl)-2-oxo-1,2-dihydropyridine-3-carbonitriles
carrying terminal di-alkoxy chain lengths (viz. octyloxy, decyloxy, dodecyloxy,
tetradecyloxy and hexadodecyloxy) as well as terminal polar groups -CN or -NO2
have been designed and synthesized successfully as luminescent mesogens. Their
thermotropic behaviors have been studied by means of differential scanning
calorimetry and polarized optical microscopy. The supramolecular organizations in
them were explored by the temperature dependent X-ray diffraction method and
their photophysical properties were investigated using UV-visible and
fluorescence spectral methods. The mesogenic study reveals that the presence of
hydrogen bonds, as well as dimerization between the molecules, is mainly
responsible for the formation of the ambient temperature hexagonal columnar phase
(Colh) in the new molecules. Their photophysical study indicates that the
compounds exhibit a strong absorption band at ~370 nm and a blue emission band at
~466 nm with good quantum yields of ~0.62 when compared to quinine sulphate (Phif
= 0.54) in chloroform. Also, the compounds show a slightly red shift in the
absorption band with increased solvent polarity. In liquid crystalline films,
they display a bathochromic shift in the emission band because of the intimate
overlap of molecular cores in the hexagonal columnar phase.
PMID- 25116729
TI - A 70-year-old kidney transplant recipient presenting with persistent leg
cellulitis.
PMID- 25116726
TI - Decreased occipital cortical glutamate levels in response to successful cognitive
behavioral therapy and pharmacotherapy for major depressive disorder.
AB - BACKGROUND: Previous studies have demonstrated that antidepressant medication and
electroconvulsive therapy increase occipital cortical gamma-aminobutyric acid
(GABA) in major depressive disorder (MDD), but a small pilot study failed to show
a similar effect of cognitive-behavioral therapy (CBT) on occipital GABA. In
light of these findings we sought to determine if baseline GABA levels predict
treatment response and to broaden the analysis to other metabolites and
neurotransmitters in this larger study. METHODS: A total of 40 MDD outpatients
received baseline proton magnetic resonance spectroscopy (1H-MRS), and 30
subjects completed both pre- and post-CBT 1H-MRS; 9 CBT nonresponders completed
an open-label medication phase followed by an additional/3rd 1H-MRS. The
magnitude of treatment response was correlated with occipital amino acid
neurotransmitter levels. RESULTS: Baseline GABA did not predict treatment
outcome. Furthermore, there was no significant effect of CBT on GABA levels.
However, we found a significant group * time interaction (F1, 28 = 6.30, p =
0.02), demonstrating reduced glutamate in CBT responders, with no significant
glutamate change in CBT nonresponders. CONCLUSIONS: These findings corroborate
the lack of effect of successful CBT on occipital cortical GABA levels in a
larger sample. A reduction in glutamate levels following treatment, on the other
hand, correlated with successful CBT and antidepressant medication response.
Based on this finding and other reports, decreased occipital glutamate may be an
antidepressant response biomarker. Healthy control comparator and nonintervention
groups may shed light on the sensitivity and specificity of these results.
PMID- 25116732
TI - Collisional energy transfer in highly excited molecules.
AB - The excitation/de-excitation step in the Lindemann mechanism is investigated in
detail using model development and classical trajectory studies based on a
realistic potential energy surface. The model, based on a soft-sphere/line-of
centers approach and using elements of Landau-Teller theory and phase space
theory, correctly predicts most aspects of the joint probability distribution
P(DeltaE,DeltaJ) for the collisional excitation and de-excitation process in the
argon-allyl system. The classical trajectories both confirm the validity of the
model and provide insight into the energy transfer. The potential employed was
based on a previously available ab initio intramolecular potential for the allyl
fit to 97418 allyl electronic energies and an intermolecular potential fit to 286
Ar-allyl energies. Intramolecular energies were calculated at the CCSD(T)/AVTZ
level of theory, while intermolecular energies were calculated at the MP2/AVTZ
level of theory. Trajectories were calculated for each of four starting allyl
isomers and for an initial rotational level of Ji = 0 as well as for Ji taken
from a microcanonical distribution. Despite a dissimilarity in Ar-allyl
potentials for fixed Ar-allyl geometries, energy transfer properties starting
from four different isomers were found to be remarkably alike. A contributing
factor appears to be that the orientation-averaged potentials are almost
identical. The model we have developed suggests that most hydrocarbons should
have similar energy transfer properties, scaled by differences in the potential
offset of the atom-hydrogen interaction. Available data corroborate this
suggestion.
PMID- 25116733
TI - Activation of peroxisome proliferator-activated receptor delta inhibits
angiotensin II-induced activation of matrix metalloproteinase-2 in vascular
smooth muscle cells.
AB - We investigated the role of peroxisome proliferator-activated receptor (PPAR)
delta on angiotensin (Ang) II-induced activation of matrix metalloproteinase
(MMP)-2 in vascular smooth muscle cells (VSMCs). Activation of PPARdelta by
GW501516, a specific ligand for PPARdelta, attenuated Ang II-induced activation
of MMP-2 in a concentration-dependent manner. GW501516 also inhibited the
generation of reactive oxygen species in VSMCs treated with Ang II. A marked
increase in the mRNA levels of tissue inhibitor of metalloproteinase (TIMP)-2 and
-3, endogenous antagonists of MMPs, was also observed in GW501516-treated VSMCs.
These effects were markedly reduced in the presence of siRNAs against PPARdelta,
indicating that the effects of GW501516 are PPARdelta dependent. Among the
protein kinases inhibited by GW501516, suppression of phosphatidylinositol 3
kinase/Akt signaling was shown to have the greatest effect on activation of MMP-2
in VSMCs treated with Ang II. Concomitantly, GW501516-mediated inhibition of MMP
2 activation in VSMCs treated with Ang II was associated with the suppression of
cell migration to levels approaching those in cells not exposed to Ang II. Thus,
activation of PPARdelta confers resistance to Ang II-induced degradation of the
extracellular matrix by upregulating expression of its endogenous inhibitor TIMP
and thereby modulating cellular responses to Ang II in vascular cells.
PMID- 25116734
TI - Hydrodehalogenation of alkyl iodides with base-mediated hydrogenation and
catalytic transfer hydrogenation: application to the asymmetric synthesis of N
protected alpha-methylamines.
AB - We report a very mild synthesis of N-protected alpha-methylamines from the
corresponding amino acids. Carboxyl groups of amino acids are reduced to
iodomethyl groups via hydroxymethyl intermediates. Reductive deiodination to
methyl groups is achieved by hydrogenation or catalytic transfer hydrogenation
under alkaline conditions. Basic hydrodehalogenation is selective for the
iodomethyl group over hydrogenolysis-labile protecting groups, such as
benzyloxycarbonyl, benzyl ester, benzyl ether, and 9-fluorenyloxymethyl, thus
allowing the conversion of virtually any protected amino acid into the
corresponding N-protected alpha-methylamine.
PMID- 25116735
TI - Alternative forms of Y-box binding protein 1 and YB-1 mRNA.
AB - The multifunctional eukaryotic protein YB-1 (Y-box binding protein 1) plays a
role in DNA reparation, transcription regulation, splicing, and mRNA translation,
thereby participating in many crucial events in cells. Its effect is dependent
mostly on its amount, and hence, on regulation of its synthesis. Published data
on regulation of synthesis of YB-1 mediated by its mRNA 5' UTR, and specifically
on the 5' UTR length and the presence of TOP-like motifs in this region, are
contradictory. Here we report that 5' UTRs of major forms of human, rabbit, and
mouse YB-1 mRNAs are about 140 nucleotides long and contain no TOP-like motifs
mentioned in the literature. Also, we have found that YB-1 specifically interacts
with the 5' UTR of its own mRNA within a region of about 100 nucleotides upstream
from the start codon. Apart from YB-1, translation of YB-1 mRNA in a cell free
system gives an additional product with an extended N-terminus and lower
electrophoretic mobility. The start codon for synthesis of the additional product
is AUC at position -(60-58) of the same open reading frame as that for the major
product. Also, in the cell there is an alternative YB-1 mRNA with exon 1 replaced
by a part of intron 1; YB-1 synthesized in vitro from this mRNA contains, instead
of its N-terminal A/P domain, 10-11 amino acids encoded by intron 1.
PMID- 25116737
TI - Three-dimensional hierarchically porous all-carbon foams for supercapacitor.
AB - Three-dimensional hierarchically porous carbon-CNT-graphene ternary all-carbon
foams (3D-HPCFs) with 3D macro- and mesoporous structures, a high specific
surface area (1286 m(2) g(-1)), large bimodal mesopores (5.1 and 2.7 nm), and
excellent conductivity have been fabricated through multicomponent surface self
assembly of graphene oxide (GO)-dispersed pristine CNTs (GOCs) supported on a
commercial sponge. The commercial sponge with a 3D interconnected macroporous
framework not only is used as a support for GOCs and subsequently multicomponent
self-assembly but also serves as a 3D scaffold to buffer electrolytes to reduce
ion transport resistance and ion diffusion distance, while the GO acts as
"surfactant" to directly disperse pristine CNTs, preserving the excellent
electronic structure of pristine CNTs, and the CNTs also prevent the aggregation
of graphene as well as improve the whole conductivity. Benefiting from the
aforementioned characteristics, the 3D-HPCFs-based supercapacitors show
outstanding specific capacitance, high rate capability, and excellent cycling
stability, making them potentially promising for high-performance energy storage
devices.
PMID- 25116736
TI - Genome-wide genotype and sequence-based reconstruction of the 140,000 year
history of modern human ancestry.
AB - We investigated ancestry of 3,528 modern humans from 163 samples. We identified
19 ancestral components, with 94.4% of individuals showing mixed ancestry. After
using whole genome sequences to correct for ascertainment biases in genome-wide
genotype data, we dated the oldest divergence event to 140,000 years ago. We
detected an Out-of-Africa migration 100,000-87,000 years ago, leading to peoples
of the Americas, east and north Asia, and Oceania, followed by another migration
61,000-44,000 years ago, leading to peoples of the Caucasus, Europe, the Middle
East, and south Asia. We dated eight divergence events to 33,000-20,000 years
ago, coincident with the Last Glacial Maximum. We refined understanding of the
ancestry of several ethno-linguistic groups, including African Americans,
Ethiopians, the Kalash, Latin Americans, Mozabites, Pygmies, and Uygurs, as well
as the CEU sample. Ubiquity of mixed ancestry emphasizes the importance of
accounting for ancestry in history, forensics, and health.
PMID- 25116738
TI - Comment on Osteocytes: masters orchestrators of bone.
PMID- 25116740
TI - Molecular modeling of potential anticancer agents from African medicinal plants.
AB - Naturally occurring anticancer compounds represent about half of the
chemotherapeutic drugs which have been put in the market against cancer until
date. Computer-based or in silico virtual screening methods are often used in
lead/hit discovery protocols. In this study, the "drug-likeness" of ~400
compounds from African medicinal plants that have shown in vitro and/or in vivo
anticancer, cytotoxic, and antiproliferative activities has been explored. To
verify potential binding to anticancer drug targets, the interactions between the
compounds and 14 selected targets have been analyzed by in silico modeling.
Docking and binding affinity calculations were carried out, in comparison with
known anticancer agents comprising ~1,500 published naturally occurring plant
based compounds from around the world. The results reveal that African medicinal
plants could represent a good starting point for the discovery of anticancer
drugs. The small data set generated (named AfroCancer) has been made available
for research groups working on virtual screening.
PMID- 25116739
TI - A prochelator with a modular masking group featuring hydrogen peroxide activation
with concurrent fluorescent reporting.
AB - Metal chelators masked with protecting groups for targeted release have the
potential to conditionally modulate cellular metals. We report a new route to
prepare cis-cinnamate protecting groups that enabled development of a prochelator
with chemical stimulus response, fluorescent reporting and active compound
release in a single structure.
PMID- 25116741
TI - In search of good ideas for occupational therapy. Previously published in
Scandinavian Journal of Occupational Therapy 1994; 1: 7-15.
AB - This paper explores the scholarly process by which good ideas may be sought for
the future development of occupational therapy as an integrated profession. It is
suggested that the assumptions of the science supporting practice need to be made
explicit and that new ideas be generated which fit the dilemmas and puzzles of
occupational therapy practice and are compatible with its view of human beings.
PMID- 25116742
TI - Towards an ADL taxonomy for occupational therapists. Previously published in
Scandinavian Journal of Occupational Therapy 1994; 1:69-76.
AB - One of the main concepts in occupational therapy is human occupation. In
occupational therapy there is a need for a common conceptual framework to assess
and describe the ability of patients to perform occupational activities of daily
living. The aim of this report was to develop a taxonomy concerning the
activities of daily living (ADL). In the taxonomy, occupation has been defined
and related to common concepts of disability. Ordinary ADL terms have been
categorized into three levels: occupational forms, activities and actions.
Different actions are components of and subordinated to superior activities.
Experience shows that the ADL taxonomy contributes to a valid (content and
construct) assessment of ADL, a common language for OTs and to a clearer picture
of the patient's performance in daily life activities.
PMID- 25116743
TI - Paradigms in occupational therapy. Previously published in Scandinavian Journal
of Occupational Therapy 1994; 1: 53-58.
AB - Every field of human occupation teems with patterns, which may be called
"paradigms". This article is concerned with paradigms in the field of
occupational therapy. The term "paradigm", which has become quite popular,
perhaps too popular since the publication of Kuhn's famous book The Structure of
Scientific Revolutions, has a complex semantic spectrum. Margaret Masterman has
distinguished no less than twenty senses in Kuhn's writings. My use of the term,
which has very little affinity with Kuhn's uses of it, will be defined in due
course.
PMID- 25116744
TI - A meditation on the use of hands. Previously published in Scandinavian Journal of
Occupational Therapy 1995; 2: 153-166.
AB - The theme of mind-body unity is fundamental to occupational therapy. Nonetheless,
the field continues to embrace a dualism of mind and body. This dualism persists
because the field views the body only as an object, ignoring how the body is
lived. Drawing upon phenomenological discussions of bodily experience, this paper
illustrates how the lived body is a locus of intelligence, intentionality,
adaptiveness, and experience. It also considers the bodily ground of motivation
and thought and discusses how the body constitutes and incorporates its world.
Finally, the paper considers implications of the lived body for therapy.
PMID- 25116745
TI - On the notion of health as ability. Previously published in Scandinavian Journal
of Occupational Therapy 1996; 3: 101-105.
AB - In this paper an outline of a theory of health based on the notion of ability is
presented. A person's health is defined as his or her second-order ability to
realize vital goals given standard or otherwise reasonable circumstances. The
crucial concepts: vital goal, standard circumstance and second-order ability, are
characterized in the paper. Special emphasis is laid upon the third concept,
second-order ability, which is of particular importance for the theory of
rehabilitation.
PMID- 25116746
TI - Time use among individuals with persistent mental illness: identifying risk
factors for imbalance in daily activities. Previously published in Scandinavian
Journal of Occupational Therapy 2008; 15: 23-33.
AB - The aim of this study was to investigate associations between time use in daily
activities and sociodemographic and clinical factors in order to identify
individuals with persistent mental illness at risk of having an imbalance in
daily activities, as reflected in their time use and daily rhythm. Participants
(n=103) were selected from a psychiatric outpatient unit using a randomized
stratified selection procedure. The main findings indicated that time spent in
daily activities increased with age, and that older individuals more often had a
beneficial daily rhythm. Women and individuals living with children spent more
time on self-care/self-maintenance than men and individuals living without
children. Individuals with a diagnosis of psychosis spent less total time in
daily activities than individuals with non-psychosis. In conclusion, general
psychiatric symptoms, such as self-blame, anxiety, and difficulties in
cooperating with others, explained most of the risk of spending little time in
work/education as well as the risk of spending long periods asleep and having an
adverse daily rhythm. A diagnosis of psychosis and high levels of general
symptoms together explained most of the risk of having low total time use in
activity. Factors such as age and living with children or not seemed to be
important factors in relation to time use and daily rhythm.
PMID- 25116747
TI - Occupational justice--bridging theory and practice. Previously published in
Scandinavian Journal of Occupational Therapy 2010; 17: 57-63.
AB - The evolving theory of occupational justice links the concept to social justice
and to concerns for a justice of difference: a justice that recognizes
occupational rights to inclusive participation in everyday occupations for all
persons in society, regardless of age, ability, gender, social class, or other
differences. The purpose of this descriptive paper is to inspire and empower
health professionals to build a theoretical bridge to practice with an
occupational justice lens. Using illustrations from a study of leisure and the
use of everyday technology in the lives of very old people in Northern Sweden,
the authors argue that an occupational justice lens may inspire and empower
health professionals to engage in critical dialogue on occupational justice; use
global thinking about occupation, health, justice, and the environment; and
combine population and individualized approaches. The authors propose that taking
these initiatives to bridge theory and practice will energize health
professionals to enable inclusive participation in everyday occupations in
diverse contexts.
PMID- 25116748
TI - The Nordic Housing Enabler: Inter-rater reliability in cross-Nordic occupational
therapy practice. Previously published in Scandinavian Journal of Occupational
Therapy 2010; 17: 258-266.
AB - This study addresses development of a content-valid cross-Nordic version of the
Housing Enabler and investigation of its inter-rater reliability when used in
occupational therapy rating situations, involving occupational therapists,
clients, and their home environments. The instrument was translated from the
original Swedish version of the Housing Enabler, and adapted according to
accessibility norms and guidelines for housing design in Sweden, Denmark,
Finland, and Iceland. This iterative process involved occupational therapists,
architects, building engineers, and professional translators, resulting in the
Nordic Housing Enabler. For reliability testing, the sampling strategy and data
collection procedures used were the same in all countries. Twenty voluntary
occupational therapists, pair-wise but independently of each other, collected
data from 106 cases by means of the Nordic Housing Enabler. Inter-rater
reliability was calculated by means of percentage agreement and kappa statistics.
Overall good percentage agreement for the personal and environmental components
of the instrument was shown, indicating that the instrument was sufficiently
reliable for application in practice and research in the Nordic context. The
varying kappa results highlight the need for further study in order to understand
the influence of prevalence more profoundly, which should be kept in mind when
interpreting the results.
PMID- 25116749
TI - Qualitative approaches in occupational therapy research. Previously published in
Scandinavian Journal of Occupational Therapy 2012; 19: 521-529.
AB - OBJECTIVE: Development of research in occupational therapy requires a continuous
critical discussion concerning methodological approaches. In this paper the
authors wish to contribute to such a discussion by introducing the Formal Data
Structure Analysis approach (FDSA) as a method for understanding people's
experiences. METHODS AND RESULTS: A review of selected publications from
occupational therapy journals between 2003 and 2005 illustrated that qualitative
articles within occupational therapy publications were mainly descriptive in
nature. This finding raises questions about how to develop new knowledge that
contributes to occupational therapy. CONCLUSIONS: In this paper the authors
suggest that it is possible to apply the FDSA approach not only when describing
and categorizing qualitative phenomena, but also when aiming to reach an in-depth
understanding of issues related to human meaning-making; for example, how we
understand engagement in occupations or living with a disability. Examples of the
application of the FDSA approach are included and discussed.
PMID- 25116750
TI - Social participation: redesign of education, research, and practice in
occupational therapy. Previously published in Scandinavian Journal of
Occupational Therapy 2013; 20: 2-8.
AB - There is growing attention to participation and social participation in
literature and policy reports. Occupational therapists strongly believe that
creating coherence between the person's occupations and environment will
facilitate participation of each individual. Nowadays, societal developments such
as "health literacy and self-management", "Web 2.0 social media", "empowering
communities", and "Nothing About Us Without Us" increase opportunities for people
to interact on different levels of social participation. Social participation can
be used as an outcome, though it can also be seen as a means to change society
and to develop solutions for barriers experienced by people with chronic diseases
or disabilities. Societal developments will have an impact on social
participation in terms of supporting each other and contributing to society.
Additionally, these changes will have a major influence on the way we educate,
conduct research, and deliver occupational therapy practice.
PMID- 25116751
TI - Occupation-centred, occupation-based, occupation-focused: same, same or
different? Previously published in Scandinavian Journal of Occupational Therapy
2013; 20: 162-173.
AB - BACKGROUND: Since the beginning of the occupational therapy profession,
engagement in occupation has been valued as the primary therapeutic agent as well
as the goal of intervention. While there are few today who would not support this
idea, occupational therapists continue to struggle with implementing their
beliefs through "what we do" and "how we do it". Contributing to this problem is
their failure to use terminology in a manner that clearly defines what and how
occupational therapists do what they do in occupational therapy research,
education, and practice. METHODS: The author will, therefore, first discuss some
key occupational therapy terms and propose that they represent an occupation
related taxonomy that can be used to more clearly define and describe for
occupational therapists and others what they do and how they do what they do as
occupational therapists. Then, with a goal of fostering critical self-reflection
among occupational scientists and occupational therapy researchers, educators,
and practitioners, the author will go through the stages of the occupational
therapy process outlined in the Occupational Therapy Intervention Process Model
(OTIPM) and demonstrate how a more precise use of this occupation-related
taxonomy can facilitate maximizing the power of occupation in practice.
PMID- 25116752
TI - Occupational therapists as contributors to health promotion. Previously published
in Scandinavian Journal of Occupational Therapy 2014; 21: 82-89.
AB - OBJECTIVE: This study was undertaken to explore the views of occupational
therapists concerning their competences in health promotion, and their
perceptions of how they apply these competences in their daily work. The study
also elicited their views on the contributions that occupational therapists could
make to health promotion if given the opportunity. METHODS: Data were collected
in five focus-group discussions with 24 occupational therapists. These
discussions were tape recorded and transcribed verbatim; data were analysed using
qualitative content analysis. RESULTS: The main findings are that the informants
took an individualized salutogenic approach in their work and rarely engaged in
health promotion on a systemic or societal level. They believed that their
patients and collaborating partners, as well as public officials, remained
unaware of their competences in health promotion. CONCLUSIONS: The findings of
this study could enrich the discussion among occupational therapists on how they
could make a more significant contribution to health promotion on a broader
level.
PMID- 25116753
TI - An investigation of the support needs of men and partners throughout the prostate
cancer journey.
AB - OBJECTIVE: Prostate cancer is one of the mostly commonly diagnosed cancers in
men. Unfortunately, the treatment for this cancer can have a number of negative
side effects, both for the man himself and his partner. This study investigated
the support needs of both men and partners throughout the prostate cancer journey
and how this journey may be optimally managed. METHODS: Thirty-one men who had
undergone prostate cancer treatment within the last 6 years and 31 partners
answered a questionnaire, which explored support care issues as identified in the
literature and from focus groups. RESULTS: Men and partners were moderately
satisfied with information given regarding diagnosis, treatment and side effects,
but partners were more satisfied with information relating to the particular
chosen treatment. Men's understanding of their chosen treatment's potential side
effects was significantly different from their understanding of diagnosis, cancer
outcome, treatment options and selected treatment. Timing of information delivery
was preferred by men at diagnosis, whereas partners preferred after the
diagnosis. Men wanted more time to think about the diagnosis and treatment,
whereas partners wanted an opportunity to discuss the diagnosis. The management
of common side effects such as emotional changes, incontinence and erectile
dysfunction was rated as 'somewhat' satisfactory. CONCLUSION: Men and partners
may have different educational and supportive needs throughout the prostate
cancer journey that require attention and tailored management.
PMID- 25116754
TI - Downregulation of MHC-I expression is prevalent but reversible in Merkel cell
carcinoma.
AB - Merkel cell carcinoma (MCC) is an aggressive, polyomavirus-associated skin
cancer. Robust cellular immune responses are associated with excellent outcomes
in patients with MCC, but these responses are typically absent. We determined the
prevalence and reversibility of major histocompatibility complex class I (MHC-I)
downregulation in MCC, a potentially reversible immune-evasion mechanism. Cell
surface MHC-I expression was assessed on five MCC cell lines using flow cytometry
as well as immunohistochemistry on tissue microarrays representing 114 patients.
Three additional patients were included who had received intralesional IFN
treatment and had evaluable specimens before and after treatment. mRNA expression
analysis of antigen presentation pathway genes from 35 MCC tumors was used to
examine the mechanisms of downregulation. Of note, 84% of MCCs (total n = 114)
showed reduced MHC-I expression as compared with surrounding tissues, and 51% had
poor or undetectable MHC-I expression. Expression of MHC-I was lower in
polyomavirus-positive MCCs than in polyomavirus-negative MCCs (P < 0.01). The MHC
I downregulation mechanism was multifactorial and did not depend solely on HLA
gene expression. Treatment of MCC cell lines with ionizing radiation, etoposide,
or IFN resulted in MHC-I upregulation, with IFNs strongly upregulating MHC-I
expression in vitro, and in 3 of 3 patients treated with intralesional IFNs. MCC
tumors may be amenable to immunotherapy, but downregulation of MHC-I is
frequently present in these tumors, particularly those that are positive for
polyomavirus. This downregulation is reversible with any of several clinically
available treatments that may thus promote the effectiveness of immune
stimulating therapies for MCC.
PMID- 25116757
TI - Dorsal thalamic nuclei in Caiman crocodilus.
AB - In Caiman crocodilus, identification of nuclei that comprise the dorsal thalamus
was determined by: injections of retrograde tracers into cortex/pallium;
injections of retrograde tracers into the noncortical telencephalon; and
injections of anterograde tracers into thalamic nuclei. With the exception of
nucleus dorsolateralis anterior, which has bilateral projections, all other
dorsal thalamic nuclei send axons to terminate in the ipsilateral telencephalon.
Nuclei that only projected to cortex/pallium were: dorsolateralis anterior;
diagonalis; and dorsal geniculate. Neuronal aggregates that send axons that
terminated in the dorsolateral area (dorsal ventricular ridge) included:
rotundus; reuniens pars centralis and pars diffusa; medialis complex posterior;
posterocentralis; and area ventrolateralis. Medialis complex anterior axons ended
in the ventrolateral area (basal ganglia). Nucleus dorsomedialis projected to
both cortex/pallium and the dorsolateral area. Based on the locus of
telencephalic termination and fiber trajectory from the dorsal thalamus, nuclei
of the dorsal thalamus were divided into several groups.
PMID- 25116758
TI - Phasic alertness in a cued double-choice reaction time task: a Contingent
Negative Variation (CNV) study.
AB - A phasic change in alertness is produced every time that a warning stimulus
precedes a target, and it enhances and maintains the response readiness to an
impending stimulus. In the present study, we investigated the Contingent Negative
Variation (CNV) phenomenon, as index of phasic alertness, during a S1-S2 paradigm
in which the imperative stimulus was represented by a double-choice reaction time
task, designed to increase the executive requests at S2. Subjects performed the
task at three consecutive time points in order to explore the CNV activity over
time. The repetition of a cued double-choice reaction time task reduced the
reaction times (RTs), while CNV amplitude remained steady along the sessions. Our
data suggest that the continuous recruitment of attentional resources does not
undergo habituation when it is related to the brain activity required in the
maintenance of working memory when the mental model of the stimulus environment
is updated.
PMID- 25116756
TI - Establishment of glycosaminoglycan assays for mucopolysaccharidoses.
AB - Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by
deficiency of the lysosomal enzymes essential for catabolism of
glycosaminoglycans (GAGs). Accumulation of undegraded GAGs results in dysfunction
of multiple organs, resulting in distinct clinical manifestations. A range of
methods have been developed to measure specific GAGs in various human samples to
investigate diagnosis, prognosis, pathogenesis, GAG interaction with other
molecules, and monitoring therapeutic efficacy. We established ELISA, liquid
chromatography tandem mass spectrometry (LC-MS/MS), and an automated high
throughput mass spectrometry (HT-MS/MS) system (RapidFire) to identify epitopes
(ELISA) or disaccharides (MS/MS) derived from different GAGs (dermatan sulfate,
heparan sulfate, keratan sulfate, and/or chondroitin sulfate). These methods have
a high sensitivity and specificity in GAG analysis, applicable to the analysis of
blood, urine, tissues, and cells. ELISA is feasible, sensitive, and reproducible
with the standard equipment. HT-MS/MS yields higher throughput than conventional
LC-MS/MS-based methods while the HT-MS/MS system does not have a chromatographic
step and cannot distinguish GAGs with identical molecular weights, leading to a
limitation of measurements for some specific GAGs. Here we review the advantages
and disadvantages of these methods for measuring GAG levels in biological
specimens. We also describe an unexpected secondary elevation of keratan sulfate
in patients with MPS that is an indirect consequence of disruption of catabolism
of other GAGs.
PMID- 25116755
TI - A feasibility study of cyclophosphamide, trastuzumab, and an allogeneic GM-CSF
secreting breast tumor vaccine for HER2+ metastatic breast cancer.
AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor
vaccines are bioactive, but limited by disease burden and immune tolerance.
Cyclophosphamide augments vaccine activity in tolerant neu mice and in patients
with metastatic breast cancer. HER2-specific monoclonal antibodies (mAb) enhance
vaccine activity in neu mice. We hypothesized that cyclophosphamide-modulated
vaccination with HER2-specific mAb safely induces relevant HER2-specific immunity
in neu mice and patients with HER2+ metastatic breast cancer. Adding both
cyclophosphamide and the HER2-specific mAb 7.16.4 to vaccination maximized HER2
specific CD8+ T-cell immunity and tumor-free survival in neu transgenic mice. We,
therefore, conducted a single-arm feasibility study of cyclophosphamide, an
allogeneic HER2+ GM-CSF-secreting breast tumor vaccine, and weekly trastuzumab in
20 patients with HER2+ metastatic breast cancer. Primary clinical trial
objectives were safety and clinical benefit, in which clinical benefit represents
complete response + partial response + stable disease. Secondary study objectives
were to assess HER2-specific T-cell responses by delayed type hypersensitivity
(DTH) and intracellular cytokine staining. Patients received three monthly
vaccinations, with a boost 6 to 8 months from trial entry. This combination
immunotherapy was safe, with clinical benefit rates at 6 months and 1 year of 55%
[95% confidence interval (CI), 32%-77%; P = 0.013] and 40% (95% CI, 19%-64%),
respectively. Median progression-free survival and overall survival durations
were 7 months (95% CI, 4-16) and 42 months (95% CI, 22-70), respectively.
Increased HER2-specific DTH developed in 7 of 20 patients [of whom 4 had clinical
benefit (95% CI, 18-90)], with a trend toward longer progression-free survival
and overall survival in DTH responders. Polyfunctional HER2-specific CD8+ T cells
progressively expanded across vaccination cycles. Further investigation of
cyclophosphamide-modulated vaccination with trastuzumab is warranted.
PMID- 25116759
TI - Disrupted MEK/ERK signaling in the medial orbital cortex and dorsal endopiriform
nuclei of the prefrontal cortex in a chronic restraint stress mouse model of
depression.
AB - Depression is one of the most prevalent mental illnesses, and causes a constant
feeling of sadness and lose of interest, which often leads to suicide. Evidence
suggests that depression is associated with aberrant MEK/ERK signaling. However,
studies on MEK/ERK signaling in depression have only been done in a few brain
regions, such as the hippocampus and mesolimbic reward pathways. Recent studies
also implicate the involvement of the prefrontal cortex in depression. Thus, we
examined the changes in MEK/ERK signaling in subregions of the prefrontal cortex
of C57BL/6 mice by immunohistochemistry using phospho-MEK1/2 (Ser 217/221) and
ERK1/2 (Thr202/Tyr204) antibodies. Mice were subjected to 21 consecutive days of
restraint stress (for 2h daily), and depression-like behavior was evaluated using
a sociability test and tail suspension test. The antidepressant, imipramine
(20mg/kg) was injected intraperitoneally 30min before restraint stress exposure.
Chronic/repeated restraint stress produced depressive-like behavior, such as
increased social avoidance in the social interaction test, and enhanced
immobility time in the tail suspension test. This depressive behavior was
ameliorated by imipramine. The behavioral changes well corresponded to a decrease
in MEK/ERK immunoreactivity in the medial orbital (MO) cortex and dorsal
endopiriform nuclei (DEn), which was averted by imipramine, but not in cingulate,
prelimbic, infralimbic, and motor cortex. These results suggest that MEK/ERK
signaling is disrupted in the DEn and MO subregions of the prefrontal cortex in
the depressive phenotype, and that blocking a decrease in activated MEK/ERK is
inherent to the antidepressant imipramine response.
PMID- 25116761
TI - Magnetic circular dichroism of porphyrin lanthanide M3+ complexes.
AB - Lanthanide complexes exhibit interesting spectroscopic properties yielding many
applications as imaging probes, natural chirality amplifiers, and therapeutic
agents. However, many properties are not fully understood yet. Therefore, we
applied magnetic circular dichroism (MCD) spectroscopy, which provides enhanced
information about the underlying electronic structure to a series of lanthanide
compounds. The metals in the M(3+) state included Y, La, Eu, Tb, Dy, Ho, Er, Tm,
Yb, and Lu; the spectra were collected for selected tetraphenylporphin (TPP) and
octaethylporphin (OEP) complexes in chloroform. While the MCD and UV-VIS
absorption spectra were dominated by the porphyrin signal, metal binding
significantly modulated them. MCD spectroscopy was found to be better suited to
discriminate between various species than absorption spectroscopy alone. The main
features and trends in the lanthanide series observed in MCD and absorption
spectra of the complexes could be interpreted at the Density Functional Theory
(DFT) level, with effective core potentials on metal nuclei. The sum over state
(SOS) method was used for simulation of the MCD intensities. The combination of
the spectroscopy and quantum-chemical computations is important for understanding
the interactions of the metals with the organic compounds.
PMID- 25116760
TI - The requirement for protein kinase C delta (PRKCD) during preimplantation bovine
embryo development.
AB - Protein kinase C (PKC) delta (PRKCD) is a member of the novel PKC subfamily that
regulates gene expression in bovine trophoblast cells. Additional functions for
PRKCD in early embryonic development in cattle have not been fully explored. The
objectives of this study were to describe the expression profile of PRKCD mRNA in
bovine embryos and to examine its biological roles during bovine embryo
development. Both PRKCD mRNA and protein are present throughout early embryo
development and increases in mRNA abundance are evident at morula and blastocyst
stages. Phosphorylation patterns are consistent with detection of enzymatically
active PRKCD in bovine embryos. Exposure to a pharmacological inhibitor
(rottlerin) during early embryonic development prevented development beyond the
eight- to 16-cell stage. Treatment at or after the 16-cell stage reduced
blastocyst development rates, total blastomere numbers and inner cell mass-to
trophoblast cell ratio. Exposure to the inhibitor also decreased basal interferon
tau (IFNT) transcript abundance and abolished fibroblast growth factor-2
induction of IFNT expression. Furthermore, trophoblast adhesion and proliferation
was compromised in hatched blastocysts. These observations provide novel insights
into PRKCD mRNA expression profiles in bovine embryos and provide evidence for
PRKCD-dependent regulation of embryonic development, gene expression and post
hatching events.
PMID- 25116763
TI - Incidence of depression in patients with chronic hepatitis C receiving
combination therapy of pegylated interferon-alpha and ribavirin.
PMID- 25116762
TI - Adverse effects of perioperative paracetamol, NSAIDs, glucocorticoids,
gabapentinoids and their combinations: a topical review.
AB - Post-operative pain affects millions of patients worldwide and the post-operative
period has high rates of morbidity and mortality. Some of this morbidity may be
related to analgesics. The aim of this review was to provide an update of current
knowledge of adverse events (AE) associated with the most common perioperative
non-opioid analgesics: paracetamol, non-steroidal anti-inflammatory drugs
(NSAIDs), glucocorticoids (GCCs), gabapentinoids and their combinations. The
review is based on data from systematic reviews with meta-analyses of analgesic
efficacy and/or adverse effects of perioperative non-opioid analgesics, and
randomised trials and cohort/retrospective studies. Generally, data on AE are
sparse and related to the immediate post-operative period. For paracetamol, the
incidence of AEs appears trivial. Data are inconclusive regarding an association
of NSAIDs with mortality, cardiovascular events, surgical bleeding and renal
impairment. Anastomotic leakage may be associated with NSAID usage. No firm
evidence exists for an association of NSAIDs with impaired bone healing. Single
dose GCCs were not significantly related to increased infection rates or delayed
wound healing. Gabapentinoid treatment was associated with increased sedation,
dizziness and visual disturbances, but the clinical relevance needs
clarification. Importantly, data on AEs of combinations of the above analgesics
are sparse and inconclusive. Despite the potential adverse events associated with
the most commonly applied non-opioid analgesics, including their combinations,
reporting of such events is sparse and confined to the immediate perioperative
period. Knowledge of benefit and harm related to multimodal pain treatment is
deficient and needs clarification in large trials with prolonged observation.
PMID- 25116764
TI - The aesthetic eye.
PMID- 25116765
TI - The methodological quality of systematic reviews comparing intravitreal
bevacizumab and alternates for neovascular age related macular degeneration: A
systematic review of reviews.
AB - OBJECTIVE: To systematically collate and evaluate the evidence from recent SRs of
bevacizumab for neo-vascular age related macular degeneration. MATERIALS AND
METHODS: Literature searches were carried out in Medline, Embase, Cochrane
databases for all systematic reviews (SRs) on the effectiveness of bevacizumab
for neo-vascular age related macular degeneration, published between 2000 and
2013. Titles and abstracts were assessed against the inclusion/exclusion criteria
using Joanna Briggs Institute (JBI) study eligibility form. Data was extracted
using the JBI data extraction form. The quality of the SRs was assessed using JBI
critical appraisal checklist for SRs. Decisions on study eligibility and quality
were made by two reviewers; any disagreements were resolved by discussion.
RESULTS: Nine relevant reviews were identified from 30 citations, of which 5
reviews fulfilled the review's inclusion criteria. All 5 reviews showed
bevacizumab to be effective for neovascular AMD in the short-term when used alone
or in combination with PDT or Pegaptanib. The average quality score of the
reviews was 7; 95% confidence interval 6.2 to 7.8 (maximum possible quality score
is 10). The selection and publication bias were not addressed in all included
reviews. Three-fifth of the reviews had a quality score of 7 or lower, these
reviews had some methodological limitations, search strategies were only
identified in 2 (40%) reviews, independent study selection and quality assessment
of included studies (4 (80%)) were infrequently performed. CONCLUSION: Overall,
the reviews on the effectiveness of intravitreal/systemic bevacizumab for
neovascular age-related macular generation (AMD) received good JBI quality
scores (mean score = 7.0 points), with a few exceptions. The study also
highlights the suboptimal reporting of SRs on this topic. Reviews with poor
methodology may limit the validity of the reported results; hence efforts should
be made to improve the design, reporting and publication of SRs across all
journals.
PMID- 25116766
TI - Nanostructure-based platforms-current prospective in ophthalmic drug delivery.
AB - The topically applied drugs as drops are washed off from the eye in very short
period, resulting in low ocular bioavailability of drugs. Number of approaches
have been attempted to increase the bioavailability and the duration of action of
ocular drugs. This review provides an insight into various novel approaches;
hydrophilic nanogels, solid lipid nanoparticles, and nanosponges applied very
recently in the delivery of insoluble drugs, prolonging the ocular residence
time, minimize pre-corneal drug loss and, therefore, bioavailability and
therapeutic efficacy of the drugs. Despite various scientific approaches,
efficient ocular drug delivery remains a challenge for pharmaceutical scientists.
PMID- 25116768
TI - The perceived personality traits of adults with digitally induced large angle
strabismus and the impact of its correction.
AB - PURPOSE: To ascertain the effect of digitally induced large angle strabismus and
its correction on social bias against strabismic adults. SUBJECTS AND METHODS:
This prospective, observational study included 10 orthotropic subjects whose face
photographs were digitally altered to produce esotropia, exotropia, and
hypertropia. Three batches of non-medical professionals, each consisting of 14
subjects, adjudged personality traits of the altered face photographs on a 10
item questionnaire. The same evaluators effected the appraisal of the orthotropic
photographs. The personality score of the strabismic photograph of a subject was
compared with its own orthotropic photograph. RESULTS: The 10 subjects whose
photographs were digitally modified were of the same age (21 years) and had equal
gender distribution. The evaluation of the photographs was performed by 42
evaluators aged 38.3 +/- 14.9 years, of whom 21 were males. Different personality
traits were rated negatively in the strabismic photographs. The statistically
significant negative impact was apparent on more number of personality traits for
esotropia (7 out of 10) as compared to exotropia (4 out of 10) or hypertropia (3
out of 10). Rating of the strabismic photographs was significantly lower by
female evaluators (P = 0.006). However, there was no difference whether the
subject evaluating the photograph of the strabismic individual was of the same
gender or the opposite gender. Internal consistency of the questionnaire was
excellent (Cronbach's Alpha = 0.81). CONCLUSION: There was a significant negative
impact of strabismus on the perceived personality traits of the digitally altered
face photographs of the adults when compared to their orthotropic photograph.
PMID- 25116769
TI - Spectral domain optical coherence tomography morphology in optic disc pit
associated maculopathy.
AB - PURPOSE: Our purpose was to study the clinical manifestation and course of optic
pit maculopathy using Spectral Domain Optical Coherence Tomography (SD- OCT)
images. MATERIALS AND METHODS: We used SD-OCT to examine 20 eyes of 19 patients
with a macular detachment in combination with an optic. RESULTS: We observed five
different fovea appearances in regard to fluid localization. In five eyes, we
recorded changes in the fluid distribution with SD-OCT. In 17/20 eyes, we noted a
communication between the perineural and subretinal and/or intraretinal space at
the margin of the optic disc. CONCLUSION: 3-dimensional SD-OCT (3D-SDOCT) scans
revealed a three-fold connection, between subretinal and intraretinal space,
perineural space, and the vitreous cavity. Therefore, we suppose that
intraretinal or subretinal fluid in optic pit maculopathy may have both a
vitreous and cerebrospinal origin. A membrane, covering the optic nerve was noted
in 14 cases. Even if it seems intact in some B-scans, it is not complete in
others several micrometers apart. Additionally, we observed fluid accumulation
below the margin of the optic disc and hyperreflective porous tissue in the optic
disc excavation. Those findings do not influence the course of maculopathy.
PMID- 25116770
TI - Comparison of ocular response analyzer parameters in primary open angle glaucoma
and exfoliative glaucoma patients.
AB - AIM: We sought to identify differences in the following measures of the ocular
response analyser (ORA) between primary open angle glaucoma (POAG) and
exfoliative glaucoma (EXG) patients: Corneal hysteresis (CH), corneal resistance
factor (CRF), corneal-compensated intraocular pressure (IOPcc) and Goldmann
correlated intraocular pressure (IOPg). We also sought to relate these ORA
measures with central corneal thickness (CCT). MATERIALS AND METHODS: This cross
sectional study was conducted on a total of 162 individuals (46 EXG patients, 66
POAG patients and 50 healthy subjects without any ocular and systemic disease).
ORA measurements were performed, and a minimum of three readings were obtained
from each test subject. Groups were compared according to their ORA parameters.
RESULTS: The mean CH levels of the EXG, POAG and healthy subjects were 7.6 +/-
2.1, 9.1 +/- 1.9 and 9.6 +/- 1.7 mmHg, respectively. CH was significantly lower
in the EXG patients compared to the other groups (P < 0.001).The mean CRF levels
of the EXG, POAG and healthy subjects were 9.0 +/- 2.0, 10.1 +/- 1.7 and 9.8 +/-
1.8mmHg, respectively. CRF levels in the eyes of the EXG patients were
significantly lower compared to those of either the POAG patients (P = 0.005) or
the healthy subjects (P = 0.03), but there was no significant difference in CRF
levels between the POAG patients and the healthy subjects (P = 0.59). There was a
significant positive correlation between CH and CCT in the EXG patients and
healthy subjects (P < 0.001), but this correlation was not present in the POAG
patients (P = 0.70). CONCLUSIONS: In this study, CH and CRF were found to be
significantly reduced in the eyes of EXG patients compared to both the POAG
patients and healthy subjects. Reduced CH in EXG patients might result in
decreased support of peripapillary scleral structure and increased damage to the
optic nerve during IOP increase.
PMID- 25116771
TI - Personal A-constant in relation to axial length with various intraocular lenses.
AB - PURPOSE: To study the relationship between the axial length and personal A
constant for the 1-piece Tecnis (Abbott ZCB00), AcrySof MA60AC (Alcon) and the
Quatrix aspheric preloaded (CROMA) intraocular lenses (IOL). MATERIALS AND
METHODS: Patients matching the inclusion criteria were further subdivided
according to the implanted IOL in this prospective comparative study. The
obtained refractive outcomes were introduced into the formula installed in the
biometry machine (Humphrey model 820 ultrasonic biometer) to obtain the personal
A-constant for each eye. Polynomial regression analysis was done to study the
individualized A-constant for each type of IOL in relation to preoperative axial
length measurement. RESULTS: Two hundred and forty five eyes of 186 patients were
enrolled into this study, of whom 73 eyes with Tecnis 1-piece, 116 eyes with
MA60AC, and 56 eyes with Quatrix. The median of personalized A-constant for
Tecnis 1-piece, MA60AC, and Quatrix were 119.21 (SD 1.3, Std. Mean error 0.15),
119 (SD 1.2, Std. Mean error 0.11) and 120.4 (SD 1.2, Std. Mean error 0.16)
respectively. Regression plots for the same range of axial length among all the
groups showed that the Tecnis1 group followed the same pattern of the Quatrix
group in which there was a linear relationship of a trend towards myopia when the
axial length had increased and a hyperopic shift when decreased. This
relationship changed into a plateau when the axial length became in the range of
23.5 mm to 27 mm in the MA60AC group. CONCLUSIONS: Personal A-constant follows
different trends with different IOLs even for the same range of axial length.
PMID- 25116772
TI - Experiences with E-learning in Ophthalmology.
AB - INTRODUCTION: E-learning is the use of internet for the purpose of education. E
learning in medical education is at a nascent stage in our country. The present
study was carried out with the purpose of introducing e-learning to third year
medical students in the subject of Ophthalmology and taking feedback on their
attitude towards the new methodology of teaching and evaluating. MATERIALS AND
METHODS: E-learning was introduced to the seventh semester students of MBBS in
the subject of Ophthalmology. The topics were converted to web friendly format
and used for teaching and evaluating. Feedback was taken from the students on
completion of the term on their attitudes towards e-learning and their views on
the scope of e-learning in medical education. RESULTS: All the students agreed on
the usefulness of e-learning in medical education. Eleven students (27.5%) found
the medium of e-learning to be interesting, 15 (37.5%) considered it to be easy
and accessible, 10 (25%) found it to be fast and easy, 4 (10%) considered it to
be a medium which can give updated information. Twenty-three (57.5%) students
considered that e-learning should be a medium of instruction in all the subjects,
15 (37.5%) students considered its usefulness in clinical subjects only. Twenty
eight students (70%) desired that e-learning should be used to provide important
notes, questions, MCQs on all topics. CONCLUSIONS: E-learning is well accepted as
a medium of instruction by medical students.
PMID- 25116773
TI - Outcomes of chronic macular hole surgical repair.
AB - PURPOSE: To report visual and anatomic outcomes of chronic macular hole surgery,
with analysis of pre-operative OCT-based hole size and post-operative closure
type. SETTINGS AND DESIGN: An IRB-approved, retrospective case series of 26 eyes
of 24 patients who underwent surgery for stage 3 or 4 idiopathic chronic macular
holes at a tertiary care referral center. STATISTICAL ANALYSIS: Student's t-test.
RESULTS: Nineteen of 26 eyes (73%) had visual improvement after surgery on most
recent exam. Twenty-one of 26 eyes (81%) achieved anatomic closure; 16 of 26 eyes
(62%) achieved type 1, and five of 26 eyes (19%) achieved type 2 closure. Post
operative LogMAR VA for type 1 closure holes (0.49) was significantly greater
than for type 2 closure and open holes (1.26, P < 0.003 and 1.10, P < 0.005,
respectively), despite similar pre-operative VA (P = 0.51 and 0.68,
respectively). Mean pre-operative hole diameter for eyes with type 1 closure,
type 2 closure, and holes that remained open were 554, 929, and 1205 microns,
respectively. Mean pre-operative hole diameter was significantly larger in eyes
that remained open as compared to eyes with type 1 closure (P = 0.015).
CONCLUSION: Vitrectomy to repair chronic macular holes can improve vision and
achieve long-term closure. Holes of greater than 3.4 years duration were
associated with a greater incidence of remaining open and type 2 closure. Larger
holes (mean diameter of 1205 microns) were more likely to remain open after
repair.
PMID- 25116774
TI - Gain beyond cosmesis: demonstration of psychosocial and functional gains
following successful strabismus surgery using the adult strabismus questionnaire
adult strabismus 20.
AB - BACKGROUND: Strabismus adversely affects psychosocial and functional aspects;
while its correction impacts positively. AIM: The aim was to evaluate the gains
in scores: Overall scores (OASs), psychosocial subscale scores (PSSs) and
functional subscale scores (FSSs) following successful surgical alignment.
SETTINGS AND DESIGN: We evaluated changed scores in the adult strabismus 20 (AS
20) questionnaire, administered before and after successful surgery. MATERIALS
AND METHODS: Thirty adults horizontal strabismics, were administered the AS-20,
at baseline, and at 6-week and 3-month. Group-wise analysis was carried out based
on gender, strabismus type (esotropia [ET] or exotropia [XT]), back-ground and
amblyopia. STATISTICAL ANALYSIS: We used Wilcoxon, and Mann-Whitney U-tests.
Significance was set at P <= 0.05. RESULTS: At baseline, there were no
significant differences within the groups, except that those with amblyopia
significantly scored less than nonamblyopes in OAS (median scores: 53.8 vs. 71.3;
P = 0.009) and FSS (56.3 vs. 85.3; P = 0.009). OAS, PSS and FSS showed
significant gains at 6-week and 3-month (all Wilcoxon P < 0.001). Compared with
males, females showed significantly more gain at 3-month (OAS: 37.9 vs. 28.7; P =
0.02), on account of PSS gain (49.6 vs. 37.5; P = 0.01). The ET performed better
than XT only on the FSS at 6-week (28.7 vs. 15.0; P = 0.02). Vis-a-vis the
nonamblyopes, the amblyopes showed significantly more benefit at 6-week alone
(OAS: 18.7 vs. 28.7; P = 0.04), largely due to gains in PSS. CONCLUSIONS:
Successful strabismus surgery has demonstrated significant gains in psychosocial,
functional and overall functions. There is some evidence that gains may be more
in females; with a trend to better outcomes in ET and amblyopes up to 6-week.
PMID- 25116776
TI - Conjunctival intraepithelial neoplasia with corneal furrow degeneration.
AB - A 68-year-old man presented with redness of left eye since six months.
Examination revealed bilateral corneal furrow degeneration. Left eye lesion was
suggestive of conjunctival squamous cell carcinoma, encroaching on to cornea.
Anterior segment optical coherence tomography (AS-OCT) confirmed peripheral
corneal thinning. Fluorescein angiography confirmed intrinsic vascularity of
lesion. Patient was managed with "no touch" surgical excision, dry keratectomy
without alcohol, cryotherapy, and primary closure. Pathologic examination of
removed tissue confirmed clinical diagnosis. Management of this particular case
required modification of standard treatment protocol. Unlike the alcohol-assisted
technique of tumor dissection described, ethyl alcohol was not used for risk of
corneal perforation due to underlying peripheral corneal thinning. Likewise,
topical steroids were withheld in the post-operative period. Three weeks post
operatively, left eye was healing well. Hence, per-operative usage of absolute
alcohol and post-operative use of topical steroids may be best avoided in such
eyes.
PMID- 25116775
TI - Scleral depressed vitreous shaving, 360 laser, and perfluoropropane (C3 F8) for
retinal detachment.
AB - Purpose : To review the characteristics and outcomes of patients who underwent
pars plana vitrectomy (PPV) with scleral depressed vitreous shaving, 360 degree
peripheral endolaser, and 14% C3F8 gas for rhegmatogenous retinal detachment
(RRD). Materials and Methods : A retrospective review of a consecutive series of
patients who underwent primary repair of RRD by PPV with scleral depressed
vitreous shaving, 360 degree peripheral endolaser, and 14% perfluoropropane (C 3
F 8 ) was conducted. Patients with less than 3 months follow-up, previous retinal
surgery, and higher than grade B proliferative vitreoretinopathy were excluded.
Results : Ninety-one eyes were included in the study. The mean age was 60.1
years. The mean follow-up was 13.7 months. The macula was detached in 63% (58/91)
of the eyes. The reattachment rate after one surgical procedure was 95% (86/91)
while overall reattachment rate was 100%. There was no statistically significant
difference between reattachment rates of superior, nasal/temporal, or inferior
RRDs. The mean final best corrected visual acuity (BCVA) was 20/40. Of all the
patients, 66% of patients with macula-off RRDs had a final BCVA of 20/40 or
better. CONCLUSIONS: PPV with scleral depressed vitreous shaving, 360 degree
peripheral endolaser, and 14% C 3 F 8 leads to successful anatomical reattachment
with visual improvement in patients with primary RRD.
PMID- 25116777
TI - Luxation of eyeball following trauma: novel simple treatment.
AB - Luxation of the eye globe is a rare occasion but it carries a risk of threat to
permanent vision loss especially when associated with very high intraocular
pressure. Appropriate intervention should be undertaken instantly. Predisposing
factors include; eyes as in shallow orbital sockets, floppy eyelid syndrome, and
exophthalmos. Prompt reduction results in restoration of full anatomical and
visual recovery in otherwise healthy eyes. We report a case of globe luxation
following trauma by door handle in a 65-year-old female, who recovered completely
after reposition of the globe using Desmarres Lid Retractors.
PMID- 25116778
TI - Feedback of final year ophthalmology postgraduates about their residency
ophthalmology training in South India.
AB - BACKGROUND AND AIMS: This study documents a survey of final-year ophthalmology
postgraduate students on the subject of their residency training. A similar
survey conducted 7 years ago published in IJO had concluded that the residency
program was not up to expectations in many centers. Our study aimed to see if
ophthalmology training and student perceptions differed since then. MATERIALS AND
METHODS: For our study, we added a few questions to the same questionnaire used
in the article "which is the best method to learn ophthalmology? Resident
doctors' perspective of ophthalmology training" published in IJO, Vol. 56 (5).
RESULTS: Forty-nine students (62.02%) returned completed forms. Most students
desired an orientation program on entering residency, and wished to undergo
diagnostic training initially. Case-presentation with demonstration and Wet-lab
learning were most preferred. There was a big difference between the number of
surgeries students actually performed and the number they felt would have been
ideal. CONCLUSION: On the whole, the students still felt the need for improved
training across all aspects of ophthalmology.
PMID- 25116779
TI - Orbital cellulitis in a neonate of the tooth bud origin: a case report.
AB - Orbital cellulitis is a serious, yet uncommon infection in neonates. It can
result in significant sight and life threatening complications. Most commonly, it
occurs secondarily as the result of a spread of infection from the sinuses.
Orbital cellulitis, secondary to dental infection is rare. We hereby report a
case of orbital cellulitis secondary to dental infection in a 15-day-old neonate
without any systemic features.
PMID- 25116780
TI - Combined special capsular tension ring and toric IOL implantation for management
of post-DALK high regular astigmatism with subluxated traumatic cataract.
AB - We report a case of 18-year-old male who has undergone phacoemulsification with
implantation of toric IOL (AcrySof IQ SN6AT9) after fixation of lens capsule with
Cionni's capsular tension ring (CTR) for subluxated traumatic cataract with high
astigmatism after deep anterior lamellar keratoplasty (DALK). He underwent right
eye DALK for advanced keratoconus four years earlier. He had history of trauma
one year later with displaced clear crystalline lens into anterior chamber and
graft dehiscence, which was repaired successfully. The graft survived, but
patient developed cataract with subluxated lens, for which phacoemulsification
with implantation of toric IOL was done. Serial topography showed regular
corneal astigmatism of -5.50 diopter (K 1 42.75 D @130 degrees , K 2 48.25 D @40
degrees ). At 10-month follow-up, the patient has BCVA 20/30 with + 0.75 DS/-
1.75 DC @ 110 degrees . The capsular bag is quite stable with well-centered IOL.
Combination of Cionni's ring with toric IOL could be a good option to manage such
complex cases.
PMID- 25116781
TI - Human ocular thelaziasis in Karnataka.
AB - Thelaziasis is an arthropod-born disease of the eye and adnexa caused by Thelazia
callipaeda, a nematode parasite transmitted by drosophilid flies to carnivores
and humans. Because of its distribution mainly confined to South Asian countries
and Russia, it is commonly known as Oriental eye worm. It is often under-reported
and not been given its due clinical importance. We report first case of human
thelaziasis from Hassan District, Karnataka. Five creamy-white, translucent worms
were removed from the conjunctival sac of a 74-year-old male patient. Based on
morphological characters, the worms were identified as nematodes belonging to the
genus Thelazia and speciation was confirmed by CDC, Atlanta as callipaeda. Rarity
of the disease and its ability to cause both extra and intraocular manifestations
leading to ocular morbidity is the reason for presenting this case. From the
available data, this is the first case report from Karnataka, India.
PMID- 25116782
TI - Spontaneous resorption of sub-retinal cortical lens material.
AB - We report a rare case of retained sub-retinal cortical material, which underwent
spontaneous resorption. Patient presented with a left eye traumatic retinal
detachment with a large retinal tear and posteriorly dislocated cataractous lens.
Vitrectomy, lensectomy, silicone oil injection, and endolaser were performed. A
good visual result was achieved. The report draws attention to this condition and
highlights possible technique for minimizing risk of this complication in similar
cases.
PMID- 25116783
TI - A study regarding efficacy of various intraocular lens power calculation formulas
in a subset of Indian myopic population.
AB - Efficacy of intraocular lens power calculation formulas in a subset of Indian
myopic population. Retrospectively reviewed 43 patients who underwent
phacoemulsification with high axial length (AL) (>24.5 mm, range 24.75-32.35 mm).
The power of the implanted intraocular lens (IOL) was used to calculate the
predicted post-operative refractive error by four formulas: Sanders-Retzlaff
Kraff (SRK II), SRK/T, Holladay 1, and Hoffer Q. The predictive accuracy of the
formulas was analyzed by comparing the difference between the "actual" and
"predicted" postoperative refractive errors. Repeated measures analysis of
variance (ANOVA) tests were done to have pair-wise comparisons between the
formulas and P < 0.05 was considered significant. A subcategory of axial length
24.5-26.5 mm was also tested. Holladay 1, Hoffer Q and SRK/T formulas showed a
slight tendency toward resultant hyperopia, with mean error of +0.24 diopters
(D), +0.58 D, and +0.92 D, respectively. The Holladay 1 formula provided the best
predictive result overall.
PMID- 25116784
TI - Anterior ischemic optic neuropathy in association with optic nervehead drusen.
AB - Optic nerve head drusen (ONHD) are incidental ophthalmologic finding in the optic
nerve. Patients with ONHD are often asymptomatic, but sometimes present with
transient visual obscuration's (TVO), the reported incidence of which is 8.6%.
Optic nerve head drusen are of two types: Superficial; visible and deep. The deep
buried drusen mimic papilledema. Because of the varied presentation deep-buried
drusen pose a diagnostic challenge to the ophthalmologists. In young patients,
they are mistaken for papilledema as it is clinically difficult to detect a
buried drusen in the optic nerve head, but are seen on the surface with aging as
the retinal nerve fiber layer thins out. They are observed as pale yellow lesions
more often located towards the poles. Clinical examination aided with diagnostic
tests like computed tomography (CT) orbits and ultrasound B scan can help
establish the diagnosis. Herein, we report a rare case of optic nerve head drusen
in a young lady, who presented with loss of vision and clinical evaluation and
investigations suggested ONHD with anterior ischemic optic neuropathy.
PMID- 25116785
TI - Using the rebound tonometer to measure intraocular pressure in an anesthetized
patient.
PMID- 25116786
TI - Isolated complete bitemporal hemianopia in traumatic chiasmal syndrome.
PMID- 25116787
TI - Massive submacular hemorrhage resulting in acute angle closure.
PMID- 25116788
TI - Treatment options for myopic CNV--is photodynamic therapy still relevant?
PMID- 25116789
TI - Varied phenotype of homocystinuria: possible diagnostic error.
PMID- 25116790
TI - Patient satisfaction with conventional, complementary, and alternative treatment
for cluster headache in a Norwegian cohort.
AB - OBJECTIVE: Cluster headache (CH) may cause excruciating pain and not all patients
get satisfactory help. Patient dissatisfaction with general practitioners (GPs)
and neurologists, and use of complementary and alternative treatment (CAM) may
reflect this. The authors studied patient satisfaction with doctors' treatment
and use of CAM in a Norwegian CH cohort. SUBJECTS: A total of 196 subjects with a
cluster headache diagnosis were identified in the registers of two neurological
departments in North Norway. DESIGN: Of these, 70 with a confirmed diagnosis
according to the second edition of the International Classification of Headache
Disorders (ICHD-2) completed a comprehensive questionnaire with questions
concerning satisfaction with doctors' treatment, use of CAM, and effect of both
treatment regimes. RESULTS: Satisfaction with doctors' treatment was reported in
44/70 (63%) (GPs) and 50/70 (71%) (neurologists) while 39/70 (56%) were satisfied
with both. Too long a time to diagnosis, median four years, was the most commonly
reported claim regarding doctors' treatment. Use of CAM was reported in 27/70
(39%), and 14/70 (20%) reported experience with >= 2 CAM. Ten patients reported
benefit from CAM (37% of "CAM users"). The average cluster period was longer in
CAM-users than others (p = 0.02), but CAM use was not associated with age,
education, use of medication, effect of conventional treatment, duration of
cluster attacks, or time to diagnosis. CONCLUSION: About two-thirds of CH
patients were satisfied with treatment from either GPs or neurologists, and about
one-third had used CAM. Despite experiencing diagnostic delay and severe pain,
cluster patients seem in general to be satisfied with doctors' conventional
treatment.
PMID- 25116791
TI - Xanthoceraside induces apoptosis in melanoma cells through the activation of
caspases and the suppression of the IGF-1R/Raf/MEK/ERK signaling pathway.
AB - Xanthoceraside, a saponin extracted from the husks of Xanthoceras sorbifolia
Bunge, suppresses inflammation and oxidative stress. However, the antitumor
properties of xanthoceraside as well as its mechanism of action remain unclear.
Therefore, we proposed to investigate its potential anticancer property. In this
study, the viability of cells was measured by the MTT assay. Cell cycle and
mitochondrial membrane potential were measured by flow cytometry, and the
expressions of procaspase-9, procaspase-3, Cyto.c, Apaf-1, Bcl-2, Bcl-xL, Bad,
p53, and IGF-1R/Raf/MEK/ERK were tested by Western blotting. Xanthoceraside
significantly inhibited the proliferation of human melanoma A375.S2 cells in a
concentration- and time-dependent manner but did not impair the viability of
normal cells (peripheral blood mononuclear cells). Further analysis revealed that
xanthoceraside induced apoptosis by activating caspase-3 and caspase-9 in a time
dependent manner through the mitochondrial pathway but did not activate caspase-8
in the cells. In addition, xanthoceraside inhibited the expression of the insulin
like growth factor-1 receptor (IGF-1R), which is an important prosurvival,
antiapoptotic signaling growth factor receptor that is frequently overexpressed
in cancer cells and used as a therapeutic target for multiple cancers.
Interestingly, xanthoceraside also decreased the expression of Raf, p-MEK, and p
ERK, the downstream effectors of IGF-1R. Taken together, these findings indicate
that xanthoceraside induces apoptosis through a mitochondria-mediated apoptotic
pathway, which is induced by the downregulation of IGF-1R/Raf/MEK/ERK cascades in
A375.S2 cells.
PMID- 25116792
TI - Long-range chemical sensitivity in the sulfur K-edge X-ray absorption spectra of
substituted thiophenes.
AB - Thiophenes are the simplest aromatic sulfur-containing compounds and are stable
and widespread in fossil fuels. Regulation of sulfur levels in fuels and
emissions has become and continues to be ever more stringent as part of
governments' efforts to address negative environmental impacts of sulfur dioxide.
In turn, more effective removal methods are continually being sought. In a
chemical sense, thiophenes are somewhat obdurate and hence their removal from
fossil fuels poses problems for the industrial chemist. Sulfur K-edge X-ray
absorption spectroscopy provides key information on thiophenic components in
fuels. Here we present a systematic study of the spectroscopic sensitivity to
chemical modifications of the thiophene system. We conclude that while the
utility of sulfur K-edge X-ray absorption spectra in understanding the chemical
composition of sulfur-containing fossil fuels has already been demonstrated, care
must be exercised in interpreting these spectra because the assumption of an
invariant spectrum for thiophenic forms may not always be valid.
PMID- 25116793
TI - Dynamin-mediated lipid acquisition is essential for Chlamydia trachomatis
development.
AB - Chlamydia trachomatis is an obligate intracellular pathogen responsible for a
high burden of human disease. Here, a loss-of-function screen using a set of
lentivirally transduced shRNAs identified 14 human host cell factors that
modulate C. trachomatis infectivity. Notably, knockdown of dynamin, a host
GTPase, decreased C. trachomatis infectivity. Dynamin functions in multiple
cytoplasmic locations, including vesicle formation at the plasma membrane and the
trans-Golgi network. However, its role in C. trachomatis infection remains
unclear. Here we report that dynamin is essential for homotypic fusion of C.
trachomatis inclusions but not for C. trachomatis internalization into the host
cell. Further, dynamin activity is necessary for lipid transport into C.
trachomatis inclusions and for normal re-differentiation from reticulate to
elementary bodies. Fragmentation of the Golgi apparatus is proposed to be an
important strategy used by C. trachomatis for efficient lipid acquisition and
replication within the host. Here we show that a subset of C. trachomatis
infected cells displayed Golgi fragmentation, which was concurrent with increased
mitotic accumulation. Golgi fragmentation was dispensable for dynamin-mediated
lipid acquisition into C. trachomatis inclusions, irrespective of the cell cycle
phase. Thus, our study reveals a critical role of dynamin in host-derived lipid
acquisition for C. trachomatis development.
PMID- 25116794
TI - A chemoenzymatic synthesis of hept-6-ene-2,5-diol stereomers: application to
asymmetric synthesis of decarestrictine L, pyrenophorol, and stagonolide E.
AB - The stereomers of hept-6-ene-2,5-diol derivatives were conceived as useful chiral
intermediates and were synthesized starting from sulcatol using two lipase
catalyzed acylation reactions as the key steps. The versatility of the
intermediates was demonstrated by converting them to the titled tetrahydropyran,
macrolide, and macrodiolide compounds using standard synthetic protocols.
PMID- 25116796
TI - AEDs at your fingertips: automated external defibrillators on college campuses
and a novel approach for increasing accessibility.
AB - The use of automated external defibrillators (AEDs) increases survival in cardiac
arrest events. Due to the success of previous efforts and free, readily available
mobile mapping software, the discussion is to emphasize the importance of the use
of AEDs to prevent sudden cardiac arrest-related deaths on college campuses and
abroad, while suggesting a novel approach to aiding in access and awareness
issues. A user-friendly mobile application (a low-cost iOS map) was developed at
Florida State University to decrease AED retrieval distance and time. The
development of mobile AED maps is feasible for a variety of universities and
other entities, with the potential to save lives. Just having AEDs installed is
not enough--they need to be easily locatable. Society increasingly relies on
phones to provide information, and there are opportunities to use mobile
technology to locate and share information about relevant emergency devices;
these should be incorporated into the chain of survival.
PMID- 25116797
TI - New methods for the synthesis of naphthyl amines; application to the synthesis of
dihydrosanguinarine, sanguinarine, oxysanguinarine and (+/-)-maclekarpines B and
C.
AB - A new method for preparing naphthyl amines from 1,5 unsaturated dicarbonyl
precursors is described; the utility of this new method was proven in the
syntheses of several natural products, all containing the benzo[c]phenanthridine
core and enabled by a radical promoted cyclisation of the naphthyl amine products
formed in the key cyclisation.
PMID- 25116798
TI - Drug-disease association and drug-repositioning predictions in complex diseases
using causal inference-probabilistic matrix factorization.
AB - The high incidence of complex diseases has become a worldwide threat to human
health. Multiple targets and pathways are perturbed during the pathological
process of complex diseases. Systematic investigation of complex relationship
between drugs and diseases is necessary for new association discovery and drug
repurposing. For this purpose, three causal networks were constructed herein for
cardiovascular diseases, diabetes mellitus, and neoplasms, respectively. A causal
inference-probabilistic matrix factorization (CI-PMF) approach was proposed to
predict and classify drug-disease associations, and further used for drug
repositioning predictions. First, multilevel systematic relations between drugs
and diseases were integrated from heterogeneous databases to construct causal
networks connecting drug-target-pathway-gene-disease. Then, the association
scores between drugs and diseases were assessed by evaluating a drug's effects on
multiple targets and pathways. Furthermore, PMF models were learned based on
known interactions, and associations were then classified into three types by
trained models. Finally, therapeutic associations were predicted based upon the
ranking of association scores and predicted association types. In terms of drug
disease association prediction, modified causal inference included in CI-PMF
outperformed existing causal inference with a higher AUC (area under receiver
operating characteristic curve) score and greater precision. Moreover, CI-PMF
performed better than single modified causal inference in predicting therapeutic
drug-disease associations. In the top 30% of predicted associations, 58.6%
(136/232), 50.8% (31/61), and 39.8% (140/352) hit known therapeutic associations,
while precisions obtained by the latter were only 10.2% (231/2264), 8.8%
(36/411), and 9.7% (189/1948). Clinical verifications were further conducted for
the top 100 newly predicted therapeutic associations. As a result, 21, 12, and 32
associations have been studied and many treatment effects of drugs on diseases
were investigated for cardiovascular diseases, diabetes mellitus, and neoplasms,
respectively. Related chains in causal networks were extracted for these 65
clinical-verified associations, and we further illustrated the therapeutic role
of etodolac in breast cancer by inferred chains. Overall, CI-PMF is a useful
approach for associating drugs with complex diseases and provides potential
values for drug repositioning.
PMID- 25116795
TI - Transcripts involved in calcium signaling and telencephalic neuronal fate are
altered in induced pluripotent stem cells from bipolar disorder patients.
AB - Bipolar disorder (BP) is a chronic psychiatric condition characterized by
dynamic, pathological mood fluctuations from mania to depression. To date, a
major challenge in studying human neuropsychiatric conditions such as BP has been
limited access to viable central nervous system tissue to examine disease
progression. Patient-derived induced pluripotent stem cells (iPSCs) now offer an
opportunity to analyze the full compliment of neural tissues and the prospect of
identifying novel disease mechanisms. We have examined changes in gene expression
as iPSC derived from well-characterized patients differentiate into neurons;
there was little difference in the transcriptome of iPSC, but BP neurons were
significantly different than controls in their transcriptional profile.
Expression of transcripts for membrane bound receptors and ion channels was
significantly increased in BP-derived neurons compared with controls, and we
found that lithium pretreatment of BP neurons significantly altered their calcium
transient and wave amplitude. The expression of transcription factors involved in
the specification of telencephalic neuronal identity was also altered. Control
neurons expressed transcripts that confer dorsal telencephalic fate, whereas BP
neurons expressed genes involved in the differentiation of ventral (medial
ganglionic eminence) regions. Cells were responsive to dorsal/ventral patterning
cues, as addition of the Hedgehog (ventral) pathway activator purmorphamine or a
dorsalizing agent (lithium) stimulated expression of NKX2-1 (ventral identity) or
EMX2 (dorsal) in both groups. Cell-based models should have a significant impact
on our understanding of the genesis and therefore treatment of BP; the iPSC cell
lines themselves provide an important resource for comparison with other
neurodevelopmental disorders.
PMID- 25116799
TI - Stimuli-responsive composite particles as solid-stabilizers for effective oil
harvesting.
AB - The polymer-grafted magnetic composite particles have been synthesized and
developed to harvest oil by use of their speical wettability. Different from
gravity-driven oil-water separation, the prepared polymer brushes-grafted
magnetic composite particles can act as solid-stabilizers that diffuse to the oil
water interfical region and effectively minimize the direct oil-water interfical
area by volume exclusion, whereas the magnetic Fe3O4 core allows easy separation
of Pickering emulsions from oil-water mixture under an external magnetic field.
When the emulsions were heated from room temperature to 50 degrees C, the coil
to-globule transition of poly(N-isopropylacrylamide) (PNIPAM) acts as the driving
force for the destabilization of the emulsion, thereby achieving the release of
oil. The novel materials can be used in aspects of oil-water separation, inducing
oil droplet transport and release of lipophilic substrates.
PMID- 25116800
TI - Stroke gait rehabilitation: is load perception a first step towards load control?
PMID- 25116802
TI - Comparison of trends and outcomes of carotid artery stenting and endarterectomy
in the United States, 2001 to 2010.
AB - BACKGROUND: Given the controversy regarding whether carotid endarterectomy (CEA)
or carotid artery stenting (CAS) may be superior for stroke prevention, it is
uncertain how recent clinical evidence, guidelines, and reimbursement policies
have influenced the volume and outcomes after these procedures. METHODS AND
RESULTS: We conducted a serial, cross-sectional study with time trends of
patients undergoing CAS (n=124 265) and CEA (n=1 260 647) between 2001 and 2010
from the Nationwide Inpatient Sample database. During the 10-year period, the
frequency of CEA declined, whereas CAS use slowly increased. After multivariate
propensity score-matched analysis, CAS was associated with an increased risk of
death (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.40-2.04), stroke
(OR, 1.43; 95% CI, 1.23-1.66), and major adverse events including death, stroke,
and myocardial infarction (OR, 1.25; 95% CI, 1.13-1.39). In asymptomatic
patients, there was no significant difference in major adverse events (OR, 1.08;
95% CI, 0.92-1.20; P=0.16 [P <0.001 for interaction between procedure type and
symptom status]) between CAS and CEA. Importantly, there was a significant
improvement in CAS outcomes during the course of 10 years (reduction in death
[OR, 0.51; 95% CI, 0.49-0.67; P for trend=0.03] and major adverse events [OR,
0.75; 95% CI, 0.66-0.84; P for trend=0.05] comparing years 2010 versus 2001).
CONCLUSIONS: In US hospitals between 2001 and 2010, CAS was associated with worse
in-hospital outcomes, partly attributable to selection and ascertainment bias.
Asymptomatic patients undergoing CAS versus CEA had similar adjusted rates of
major adverse events. CAS outcomes improved significantly during the course of
the decade likely attributable to improvements in patient selection, operator
skills, and technological advancements.
PMID- 25116801
TI - A mutation in the CASQ1 gene causes a vacuolar myopathy with accumulation of
sarcoplasmic reticulum protein aggregates.
AB - A missense mutation in the calsequestrin-1 gene (CASQ1) was found in a group of
patients with a myopathy characterized by weakness, fatigue, and the presence of
large vacuoles containing characteristic inclusions resulting from the
aggregation of sarcoplasmic reticulum (SR) proteins. The mutation affects a
conserved aspartic acid in position 244 (p.Asp244Gly) located in one of the high
affinity Ca(2+) -binding sites of CASQ1 and alters the kinetics of Ca(2+) release
in muscle fibers. Expression of the mutated CASQ1 protein in COS-7 cells showed a
markedly reduced ability in forming elongated polymers, whereas both in cultured
myotubes and in in vivo mouse fibers induced the formation of electron-dense SR
vacuoles containing aggregates of the mutant CASQ1 protein that resemble those
observed in muscle biopsies of patients. Altogether, these results support the
view that a single missense mutation in the CASQ1 gene causes the formation of
abnormal SR vacuoles containing aggregates of CASQ1, and other SR proteins,
results in altered Ca(2+) release in skeletal muscle fibers, and, hence, is
responsible for the clinical phenotype observed in these patients.
PMID- 25116803
TI - alpha-Solanine inhibits invasion of human prostate cancer cell by suppressing
epithelial-mesenchymal transition and MMPs expression.
AB - alpha-Solanine, a naturally occurring steroidal glycoalkaloid found in nightshade
(Solanum nigrum Linn.), was found to inhibit proliferation and induce apoptosis
of tumor cells. However, the mechanism involved in suppression of cancer cell
metastasis by alpha-solanine remains unclear. This study investigates the
suppression mechanism of alpha-solanine on motility of the human prostate cancer
cell PC-3. Results show that alpha-solanine reduces the viability of PC-3 cells.
When treated with non-toxic doses of alpha-solanine, cell invasion is markedly
suppressed by alpha-solanine. alpha-Solanine also significantly elevates
epithelial marker E-cadherin expression, while it concomitantly decreases
mesenchymal marker vimentin expression, suggesting it suppresses epithelial
mesenchymal transition (EMT). alpha-Solanine reduces the mRNA level of matrix
metalloproteinase-2 (MMP-2), MMP-9 and extracellular inducer of matrix
metalloproteinase (EMMPRIN), but increases the expression of reversion-inducing
cysteine-rich protein with kazal motifs (RECK), and tissue inhibitor of
metalloproteinase-1 (TIMP-1) and TIMP-2. Immunoblotting assays indicate alpha
solanine is effective in suppressing the phosphorylation of phosphatidylinositide
3 kinase (PI3K), Akt and ERK. Moreover, alpha-solanine downregulates oncogenic
microRNA-21 (miR-21) and upregulates tumor suppressor miR-138 expression. Taken
together, the results suggest that inhibition of PC-3 cell invasion by alpha
solanine may be, at least in part, through blocking EMT and MMPs expression.
alpha-Solanine also reduces ERK and PI3K/Akt signaling pathways and regulates
expression of miR-21 and miR-138. These findings suggest an attractive
therapeutic potential of alpha-solanine for suppressing invasion of prostate
cancer cell.
PMID- 25116804
TI - Self-assembled micelles composed of doxorubicin conjugated Y-shaped PEG
poly(glutamic acid)2 copolymers via hydrazone linkers.
AB - In this work, micelles composed of doxorubicin-conjugated Y-shaped copolymers
(YMs) linked via an acid-labile linker were constructed. Y-shaped copolymers of
mPEG-b-poly(glutamate-hydrazone-doxorubicin)2 and linear copolymers of mPEG-b
poly(glutamate-hydrazone-doxorubicin) were synthesized and characterized.
Particle size, size distribution, morphology, drug loading content (DLC) and drug
release of the micelles were determined. Alterations in size and DLC of the
micelles could be achieved by varying the hydrophobic block lengths. Moreover, at
fixed DLCs, YMs showed a smaller diameter than micelles composed of linear
copolymers (LMs). Also, all prepared micelles showed sustained release behaviors
under physiological conditions over 72 h. DOX loaded in YMs was released more
completely, with 30% more drug released in acid. The anti-tumor efficacy of the
micelles against HeLa cells was evaluated by MTT assays, and YMs exhibited
stronger cytotoxic effects than LMs in a dose- and time-dependent manner.
Cellular uptake studied by CLSM indicated that YMs and LMs were readily taken up
by HeLa cells. According to the results of this study, doxorubicin-conjugated Y
shaped PEG-(polypeptide)2 copolymers showed advantages over linear copolymers,
like assembling into smaller nanoparticles, faster drug release in acid, which
may correspond to higher cellular uptake and enhanced extracellular/intracellular
drug release, indicating their potential in constructing nano-sized drug delivery
systems.
PMID- 25116805
TI - Ruthenium polypyridine complexes combined with oligonucleotides for bioanalysis:
a review.
AB - Ruthenium complexes are among the most interesting coordination complexes and
they have attracted great attention over the past decades due to their appealing
biological, catalytic, electronic and optical properties. Ruthenium complexes
have found a unique niche in bioanalysis, as demonstrated by the substantial
progress made in the field. In this review, the applications of ruthenium
complexes coordinated with polypyridine ligands (and analogues) in bioanalysis
are discussed. Three main detection methods based on electrochemistry,
electrochemiluminescence, and photoluminscence are covered. The important
targets, including DNA and other biologically important targets, are detected by
specific biorecognition with the corresponding oligonucleotides as the
biorecognition elements (i.e., DNA is probed by its complementary strand and
other targets are detected by functional nucleic acids, respectively). Selected
examples are provided and thoroughly discussed to highlight the substantial
progress made so far. Finally, a brief summary with perspectives is included.
PMID- 25116806
TI - Synthesis, immobilization and catalytic activity of a copper(II) complex with a
chiral bis(oxazoline).
AB - A chiral bis(oxazoline) bearing CH2OH groups was synthesized from a commercial
bis(oxazoline) and characterized by 1H- and 13C-NMR, high resolution ESI-mass
spectrometry and FTIR. The corresponding copper(II) complex was immobilized onto
the surface of a mesoporous carbonaceous material (Starbon(r) 700) in which the
double bonds had been activated via conventional bromination. The materials were
characterized by elemental analysis, ICP-OES, XPS, thermogravimetry and nitrogen
adsorption at 77 K. The new copper(II) bis(oxazoline) was tested both in the
homogeneous phase and once immobilized onto a carbonaceous support for the
kinetic resolution of hydrobenzoin. Both were active, enantioselective and
selective in the mono-benzoylation of hydrobenzoin, but better
enantioselectivities were obtained in the homogeneous phase. The heterogeneous
catalyst could be separated from the reaction media at the end of the reaction
and reused in another catalytic cycle, but with loss of product yield and
enantioselectivity.
PMID- 25116807
TI - Dissociative electron transfer to diphenyl-substituted bicyclic endoperoxides:
the effect of molecular structure on the reactivity of distonic radical anions
and determination of thermochemical parameters.
AB - The heterogeneous electron transfer reduction of the bicyclic endoperoxide 1,4
diphenyl-2,3-dioxabicyclo[2.2.1]hept-5-ene (4) was investigated in N,N
dimethylformamide at a glassy carbon electrode. The endoperoxide reacts by a
concerted dissociative ET mechanism resulting in reduction of the O-O bond with
an observed peak potential of -1.4 V at 0.2 V s-1. The major product (90% yield)
resulting from the heterogeneous bulk electrolysis of 4 at -1.4 V with a rotating
disk glassy carbon electrode is 1,4-diphenyl-cyclopent-2-ene-cis-1,3-diol with a
consumption of 1.73 electrons per mole. In contrast, 1,4-diphenyl-2,3
dioxabicyclo[2.2.2]oct-5-ene (1), undergoes a two-electron reduction mechanism in
quantitative yield. This difference in product yield between 1 and 4 is
suggestive of a radical-anion mechanism, as observed with 1,4-diphenyl-2,3
dioxabicyclo-[2.2.2] octane (2) and 1,4-diphenyl-2,3-dioxabicyclo[2.2.1]heptane
(3). Convolution potential sweep voltammetry is used to determine unknown
thermochemical parameters of 4, including the O-O bond dissociation energy and
the standard reduction potential and a comparison is made to the previously
studied bicyclic endoperoxides 1-3 with respect to the effect of molecular
structure on the reactivity of distonic radical anions.
PMID- 25116809
TI - A novel mitovirus from Buergenerula spartinae infecting the invasive species
Spartina alterniflora.
PMID- 25116808
TI - Effect of chitosan on tobacco mosaic virus (TMV) accumulation, hydrolase
activity, and morphological abnormalities of the viral particles in leaves of N.
tabacum L. cv. Samsun.
AB - The effect of chitosan on the development of infection caused by Tobacco mosaic
virus (TMV) in leaves of Nicotiana tabacum L. cv. Samsun has been studied. It was
shown that the infectivity and viral coat protein content in leaves inoculated
with a mixture of TMV (2 MUg/mL) and chitosan (1 mg/mL) were lower in the early
period of infection (3 days after inoculation), by 63% and 66% respectively, than
in leaves inoculated with TMV only. Treatment of leaves with chitosan 24 h before
inoculation with TMV also caused the antiviral effects, but these were less
apparent than when the virus and polysaccharide were applied simultaneously. The
inhibitory effects of the agent decreased as the infection progressed.
Inoculation of leaves with TMV together with chitosan considerably enhanced the
activity of hydrolases (proteases, RNases) in the leaves, in comparison with
leaves inoculated with TMV alone. Electron microscope assays of phosphotungstic
acid (PTA)-stained suspensions from infected tobacco leaves showed that, in
addition to the normal TMV particles (18 nm in diameter, 300 nm long), these
suspensions contained abnormal (swollen, "thin" and "short") virions. The highest
number of abnormal virions was found in suspensions from leaves inoculated with a
mixture of TMV and chitosan. Immuno-electron microscopy showed that "thin" virus
particles, in contrast to the particles of normal diameter, lost the ability to
bind to specific antiserum. It seems that the chitosan-induced activation of
hydrolases stimulates the intracellular degradation of TMV particles and hence
hydrolase activation may be considered to be one of the polysaccharide-mediated
cellular defense mechanisms that limit virus accumulation in cells.
PMID- 25116810
TI - Alterations of the synapse of the inner retinal layers after chronic intraocular
pressure elevation in glaucoma animal model.
AB - BACKGROUND: Dendrites of retinal ganglion cells (RGCs) synapse with axon
terminals of bipolar cells in the inner plexiform layer (IPL). Changes in RGC
dendrites and synapses between bipolar cells in the inner retinal layer may
critically alter the function of RGCs in glaucoma. Recently, synaptic plasticity
has been observed in the adult central nervous system, including the outer
retinal layers. However, few studies have focused on changes in the synapses
between RGCs and bipolar cells in glaucoma. In the present study, we used a rat
model of ocular hypertension induced by episcleral vein cauterization to
investigate changes in synaptic structure and protein expression in the inner
retinal layer at various time points after moderate intraocular pressure (IOP)
elevation. RESULTS: Synaptophysin, a presynaptic vesicle protein, increased
throughout the IPL, outer plexiform layer, and outer nuclear layer after IOP
elevation. Increased synaptophysin after IOP elevation was expressed in bipolar
cells in the innermost IPL. The RGC marker, SMI-32, co-localized with
synaptophysin in RGC dendrites and were significantly increased at 1 week and 4
weeks after IOP elevation. Both synaptophysin and postsynaptic vesicle protein,
PSD-95, were increased after IOP elevation by western blot analysis. Ribbon
synapses in the IPL were quantified and structurally evaluated in retinal
sections by transmission electron microscopy. After IOP elevation the total
number of ribbon synapses decreased. There were increases in synapse diameter and
synaptic vesicle number and decreases in active zone length and the number of
docked vesicles after IOP elevation. CONCLUSIONS: Although the total number of
synapses decreased as RGCs were lost after IOP elevation, there are attempts to
increase synaptic vesicle proteins and immature synapse formation between RGCs
and bipolar cells in the inner retinal layers after glaucoma induction.
PMID- 25116813
TI - Tools of the Trade: a tribute to Karen Denard Goldman, PhD, MCHES.
PMID- 25116812
TI - Preparation of highly efficient MRI contrast agents through complexation of
cationic Gd(III)-containing metallosurfactant with biocompatible
polyelectrolytes.
AB - Novel contrast agents were developed through assembling of Gd(III) -containing
metallosurfactant (MS) with biocompatible polyelectrolytes sodium hyaluronate
(HA), heparinsodium (HS) and dextran sulfate sodium (DSS). The formed
polyelectrolyte-surfactant complexes showed different structural patterns as the
charge ratio increased, including spherical aggregates, rod-like aggregates and
network patterns in monovalent HA system, while spherical structures emerged in
multivalent HS and DSS systems. Energy dispersive spectroscopy analysis and
scanning electron microscopy mapping showed the presence of Gd(III) in these
complexes. Inductively coupled plasma atomic emission spectrometry was further
used to quantify the contents of Gd(III) in the assemblies. T1 magnetic resonance
imaging showed that these Gd(III) -loaded complexes exhibited relaxivity of up to
63.81 mM(-1) s(-1) , much higher than that of Ominiscan (4.64 mM(-1) s(-1) ).
The cytotoxicity test in vitro demonstrated the excellent biocompatibility of
these complexes, which is essential for clinical application.
PMID- 25116811
TI - Periodontal regeneration using strontium-loaded mesoporous bioactive glass
scaffolds in osteoporotic rats.
AB - Recent studies demonstrate that the rate of periodontal breakdown significantly
increased in patients compromised from both periodontal disease and osteoporosis.
One pharmacological agent used for their treatment is strontium renalate due to
its simultaneous ability to increase bone formation and halt bone resorption. The
aim of the present study was to achieve periodontal regeneration of strontium
incorporated mesoporous bioactive glass (Sr-MBG) scaffolds in an osteoporotic
animal model carried out by bilateral ovariectomy (OVX). 15 female Wistar rats
were randomly assigned to three groups: control unfilled periodontal defects, 2)
MBG alone and 3) Sr-MBG scaffolds. 10 weeks after OVX, bilateral fenestration
defects were created at the buccal aspect of the first mandibular molar and
assessed by micro-CT and histomorphometric analysis after 28 days. Periodontal
fenestration defects treated with Sr-MBG scaffolds showed greater new bone
formation (46.67%) when compared to MBG scaffolds (39.33%) and control unfilled
samples (17.50%). The number of TRAP-positive osteoclasts was also significantly
reduced in defects receiving Sr-MBG scaffolds. The results from the present study
suggest that Sr-MBG scaffolds may provide greater periondontal regeneration.
Clinical studies are required to fully characterize the possible beneficial
effect of Sr-releasing scaffolds for patients suffering from a combination of
both periodontal disease and osteoporosis.
PMID- 25116814
TI - Tools of the Trade: a tribute to Karen Denard Goldman, PhD, MCHES.
PMID- 25116815
TI - Neuropathic pain in two-generation twins carrying the sodium channel Nav1.7
functional variant R1150W.
AB - We present clinical, neuropathological, and molecular genetic findings of a
family with a new pain phenotype of the sodium channel gene SCN9A polymorphism
R1150W. A 46-year-old woman presented with a 5-year history of episodic
temperature- and exercise-dependent burning pain of the feet and lower legs
associated with numbness of the distal upper and lower limbs. Her monozygotic
twin sister and their mother and her twin presented similar symptoms. Clinical
evaluation was normal except for a mild distal sensory deficit in fingers and
feet. Electrophysiological testing was unremarkable, as were serum and
cerebrospinal fluid laboratory findings. Skin biopsies of the distal lower limbs
revealed an epidermal nerve fiber density at the lower limit of normal.
Myelinated dermal nerve fibers showed elongated nodes of Ranvier, but normal
distribution of nodal and paranodal proteins. Genetic testing for ion channel
associated pain disorders revealed an amino acid R1150W substitution of the
Nav1.7 sodium channel. The combination of a Nav1.7 polymorphism with
dysmyelinating features in small-caliber peripheral nerves has not been described
before and may suggest an explanation for the clinical syndrome in our patients.
Treatment with the sodium channel blocker lamotrigine provided some relief,
consistent with a role of sodium channel dysfunction in the pain syndrome of this
family.
PMID- 25116816
TI - A gamma-butyrolactone-sensing activator/repressor, JadR3, controls a regulatory
mini-network for jadomycin biosynthesis.
AB - Two regulatory genes, jadR2 and jadR3, in the jadomycin (jad) biosynthetic gene
cluster of Streptomyces venezuelae encode homologues of gamma-butyrolactone
receptor. JadR2 was previously shown to be a pseudo gamma-butyrolactone receptor.
jadR3 is situated at the upstream of jadW123 encoding putative enzymes for gamma
butyrolactone biosynthesis. Disruption of jadR3 resulted in markedly decreased
production of jadomycin. Transcriptional analysis revealed that JadR3 represses
jadW1, jadR2 and jadR3 but activates jadR1, the key activator gene for jadomycin
biosynthesis. DNase I footprinting showed that JadR3 has four binding sites in
the intergenic regions of jadR2-jadR1 and jadR3-jadW1. A JadR3 interactive
molecule, SVB1, was purified from a large-scale fermentation and its structure
found to be the same as SCB3, a gamma-butyrolactone from Streptomyces coelicolor,
and was absent from a jadW123 mutant lacking jadomycin production. Addition of
SVB1 or extract from S. coelicolor to the mutant restored jadomycin production.
Overall, our results revealed that the association of JadR3 and SVB1 plays an
important role in controlling a regulatory mini-network governing jadomycin
biosynthesis, providing new insights into the ways in which gamma
butyrolactone/receptor systems modulate antibiotic biosynthesis in Streptomyces.
PMID- 25116818
TI - Implication of the Seoul declaration on public health of India.
PMID- 25116817
TI - Somatization symptoms or interferon-related adverse events? Alexithymia and
somatization in somatic symptom reporting of patients with chronic hepatitis C.
PMID- 25116819
TI - Who's failure? encephalitis kills!
AB - Encephalitis continues to be one of the most dreaded diagnoses because a high
rate of morbidity and mortality are accepted even before starting the treatment.
Most encephalitis cases occur in rural areas due to poor environmental
sanitation, high-vector density, shortage of protected water supplies and lack of
health education. Vaccination, environmental sanitation, vector control, health
education and attention to prompt diagnosis and treatment in rural hospitals are
the four essential pillars for reducing case fatality rate (CFR) of encephalitis.
Frequently, virulence of the virus, immunological state of the host,
unavailability of antiviral drugs and lack of enough tertiary care hospitals
(TCH) are not responsible for the high CFR. Basic supportive care is not being
practiced meticulously in Primary and Secondary Care Hospitals (PSCH), and their
services are not being utilized fully. Main causes of high mortality and
morbidity rates are hypoxia and ischemia of brain and other organs precipitated
by preventable, controllable or treatable complications due to lack of basic
medical and nursing care during transport to the TCH. Undiagnosed Rickettsial
infections are suspected to be partly responsible for the high CFR in some areas.
Improving rural hospitals and their ambulance services are the most economical
way to reduce CFR. "Treatment facilities must be made available at places where
cases occur." The best way to reduce CFR of encephalitis in developing and
underdeveloped countries is to increase and improve PSCH and sensitize
politicians, administrators, medical/nursing professionals and more importantly
to impress and convince the public to utilize them.
PMID- 25116820
TI - Public health challenges for universal health coverage.
AB - The effective functioning of any health system requires an efficient public
health service. Every human being has the right to enjoy "the highest attainable
standard of health," which can be fulfilled by giving every man an affordable and
equitable health system he deserves and demands. In these years, complex health
changes have complicated the situation in India. Most important gaps in the
health care include an understanding of the burden of the disease and what leads
to and causes ill health, the availability and use of appropriate technology in
the management of disease, ill health and health systems that have an impact on
service delivery. Universal Health Coverage (UHC) has the potential to increase
economic growth, improve educational opportunities, reduce impoverishment and
inequalities, and foster social cohesion. Steps taken for achieving UHC will
address the public health challenges and vice versa.
PMID- 25116821
TI - Universal health coverage: the way forward.
AB - Universal health coverage (UHC) is the means to provide accessible and
appropriate health services to all citizens without financial hardships. India,
an emerging economy with demographic window of opportunity has been facing dual
burden of diseases in midst of multiple transitions. Health situation in the
country despite quantum improvements in recent past has enormous challenges with
urban-rural and interstate differentials. Successful national programs exists,
but lack ability to provide and sustain UHC. Achieving UHC require sustained
mechanisms for health financing and to provide financial protection through
national health packages. There is a need to ensure universal access to
medicines, vaccines and emerging technologies along with development of Human
Resources for Health (HRH). Health service, management, and institutional reforms
are required along with enhanced focus on social determinants of health and
citizen engagement. UHC is the way for providing health assurance and enlarging
scope of primary health care to nook and corners of the country.
PMID- 25116822
TI - Assessment of quality of life during treatment of pediatric oncology patients.
AB - BACKGROUND: The objective of this study was to assess health-related quality of
life (HRQOL) of pediatric cancer patients and their parents in North India.
MATERIALS AND METHODS: Seventy-five cancer children were assessed for HRQOL,
using Lansky play performance scale and health utility index-2 (HUI-2). Fifty
seven patients were followed-up after 4 months after therapy and reassessed.
Their parents were also assessed using World Health Organisation (WHO) QOL BREF.
Seventy five controls were also assessed and compared. RESULTS: Lansky and HUI-2
scores of patients, as well as WHO QOL BREF of parents were significantly poor in
cancer patients when compared to controls. There was significant improvement
after therapy in patients with lymphomas and miscellaneous tumors. Pain and self
care were found to be maximally affected domains on HUI-2. CONCLUSIONS: Large
prospective multicenter studies may be undertaken and hence that need based
interventions can be planned.
PMID- 25116823
TI - Health status and health care services in Uttar Pradesh and Bihar: a comparative
study.
AB - BACKGROUND: India's growth hype and dream of emerging as an economic superpower
are being challenged today, among other things, by its failure to foster an
inclusive growth path and provide to bulk of its population basic amenities of
education and health. There exists great inequality at interstate and intrastate
level in terms of the key components of human development-health and education.
AIMS: The present work attempts to measure the extent of the inequality in health
status and health care services in the two most populous states of India namely
Uttar Pradesh and Bihar. MATERIALS AND METHODS: A detailed analysis of
interdistrict and interregion disparity in health status and health care in the
two states has been done using secondary data from Annual Health Survey (2011)
and Statistical Diary (2011). Composite indices of health status and health
services have been developed using Maher's normalization technique and principal
component analysis. Inequality measures like co-efficient of variations have been
used to measure the relevant disparities in the two states and explain the reason
thereof. RESULTS: The work shows low overall health status and wide interdistrict
and interregion health disparity in the two states with lower disparity in Uttar
Pradesh as compared to Bihar in terms of health status and relatively high
disparity in health infrastructure. One startling fact is existence of very low
and insignificant correlation between infrastructure and outcome. CONCLUSION: The
study finds health status is influenced not only by health care facilities, but a
number of other factors principally government's commitment and policies.
PMID- 25116824
TI - Prescribing behavior of diabetes treating physicians in selected health care
facilities of the diabetic association of Bangladesh.
AB - BACKGROUND: Practicing behavior of the physicians varies from population to
population due to diverse socioeconomic, cultural, and professional factors.
Evidence on these issues is almost nonexistent in the developing countries.
OBJECTIVE: The prescribing behavior of diabetes treating physicians working in
selected hospitals of the Diabetic Association of Bangladesh was studied along
with the factors affecting those behaviors. MATERIALS AND METHODS: This was an
observational study on 818 prescriptions given by 49 physicians working in 16
health care facilities, which were photocopied by a portable photocopier. The
various components of the prescription were scrutinized for presence and absence,
and evaluated independently by two expert Diabetologists for their qualitative
aspects. RESULTS: The mean +/- standard deviation of the total prescribing score
(expressed as percentage) was 60 +/- 11. Physicians scoring around or below 60%
belonged more to lower age (<40 years), less experienced (<7 years) and mid
position (Senior Medical Officers) groups. Most of them also had public medical
college background. Physicians with Certificate Course on Diabetology (CCD) had
significantly higher score compared with the Non-CCD group (P < 0.001). Direction
and duration of drug use were absent in majority of prescriptions (72.0% and
61.6%), respectively. Symptoms were not written in 78.0% and the family histories
were not recorded in 98.5% prescriptions. Diet (49.4%) and exercise (51.0%)
related advices were not mentioned in a large number of prescriptions.
Appropriate change of drug (78.2%) and proper use of drug (99.1%) and brand
(93.8%) were found rational, but still, 22.4% of the prescriptions found
illegible. CONCLUSION: A large proportion of prescriptions in Bangladesh related
to diabetes care still lack standardization and acceptable quality. Nondrug
related issues (such as history, symptoms, and dietary/exercise-related advices)
are the most neglected ones in a prescription.
PMID- 25116825
TI - Trends of chronic liver disease in a tertiary care referral hospital in Eastern
India.
AB - BACKGROUND: There is scarce Indian data on time trends of hepatitis, an
impediment to formulate an effective public health policy on the matter.
OBJECTIVE: The aim was to study secular trends and burden of hepatitis in a
railway population. MATERIALS AND METHODS: Outdoor, indoor, endoscopy unit and
mortality records of patients attending this hospital from January 2003 to
December 2011 were searched manually and relevant parameters of hepatitis
patients were noted, especially etiology, clinical features, treatment, and
mortality. Cochran-Armitage trend test was used to test significance of any trend
in these parameters. Binary logistic regression analysis of various factors was
carried out to study their effect on the liver related mortality of hepatitis B
and C cases and Kaplan-Meyer survival curves were generated for significant
factors. Two-sided P < 0.05 was considered to be significant. RESULT: Chronic
liver disease (CLD) due to alcohol showed a significant rising trend with early
age (mean 48.4 years) and high percentage of decompensated disease (75%) at
presentation and high early mortality (63%). No trend was observed for hepatitis
B and C, but significant reduction in mortality was observed when definitive
therapy was given. Cryptogenic CLD showed a decreasing trend though overall it
still remained the most important etiology and survival was better compared with
alcohol even with conservative therapy. Only 4% patients had hepatocellular
carcinoma. CONCLUSION: A menace of alcohol related liver disease affecting young
productive work force in this part of India is foreseen, which might impact the
country's economy and mandates immediate containment policy.
PMID- 25116827
TI - Obstetric near miss morbidity and maternal mortality in a Tertiary Care Centre in
Western Rajasthan.
AB - Obstetric near-miss (ONM) describes a situation of lethal complication during
pregnancy, labor or puerperium in which the woman survives either because of
medical care or just by chance. In a cross-sectional observational study, five
factor scoring system was used to identify the near-miss cases from all the cases
of severe obstetric morbidity. Assessment of the causes of maternal mortality and
near-miss obstetric cases was done. The ONM rate in this study was 4.18/1000 live
births. Totally 54 maternal deaths occurred during this period, resulting in a
ratio of 202 maternal deaths per 100,000 live births. Hemorrhage, hypertension
and sepsis were major causes of near-miss maternal morbidity and mortality,
respectively in descending order.
PMID- 25116826
TI - Prevalence of behavioral risk factors, overweight and hypertension in the urban
slums of North 24 Parganas District, West Bengal, India, 2010.
AB - Globally, 1 billion people live in slums. There are few reports of high
prevalence of noncommunicable disease (NCD) risk factors among the urban poor.
The prevalence of NCD risk factors in the slums in North 24 Parganas, West
Bengal, India was estimated. Cross-sectional survey in 24 slums selected using
cluster sampling method was conducted. Questionnaire for behavioral risk factors
was used and anthropometric and blood pressure measurements were done. The study
population included 1052 participants aged 25-64 years, 528 (50%) were males.
Among males, 206 (39%) were current smokers and 154 (29%) were current alcohol
users. Central obesity was prevalent among 32.8% males and 56.1% females and 115
(10.9%) had body mass index >=27.5 kg/m 2 . Hypertension was prevalent among 35%
males and 33% females. We observed high prevalence of NCD risk factors among
urban slum dwellers that need to be addressed with health promotion programs and
strengthening of primary health care system.
PMID- 25116828
TI - Prevalence and risk factors for Taenia solium taeniasis in Kaniyambadi block,
Tamil Nadu, South India.
PMID- 25116829
TI - The hookah experience: stop them before it's too late!!!!
PMID- 25116830
TI - Public health dentistry education program in India.
PMID- 25116831
TI - Modeling Zn2+ release from metallothionein.
AB - Mammalian metallothioneins (MTs) comprise a Zn3Cys9 cluster in the beta domain
and a Zn4Cys11 cluster in the alpha domain. They play a crucial role in storing
and donating Zn(2+) ions to target metalloproteins and have been implicated in
several diseases, thus understanding how MTs release Zn(2+) is of widespread
interest. In this work, we present a strategy to compute the free energy for
releasing Zn(2+) from MTs using a combination of classical molecular dynamics
(MD) simulations, quantum-mechanics/molecular-mechanics (QM/MM) minimizations,
and continuum dielectric calculations. The methodology is shown to reproduce the
experimental observations that (1) the Zn-binding sites do not have equal Zn(2+)
affinity and (2) the isolated beta domain is thermodynamically less stable and
releases Zn(2+) faster with oxidizing agents than the isolated alpha domain. It
was used to compute the free energies for Zn(2+) release from the metal cluster
in the absence and presence of the protein matrix (protein architecture and
coupled protein-water interactions) to yield the respective disulfide-bonded
product. The results show the importance of the protein matrix as well as protein
dynamics and coupled conformational changes in accounting for the differential
Zn(2+)-releasing propensity of the two domains with oxidizing agents.
PMID- 25116832
TI - Catalytic asymmetric reactions by metal and chiral phosphoric acid sequential
catalysis.
AB - Catalytic asymmetric reactions promoted by metal catalysts and chiral phosphoric
acids have become useful processes for the preparation of structurally diverse
and complex organic compounds. This JOCSynopsis provides an overview of the most
recent developments made in studies of these reactions. The paper focuses mainly
on sequential catalysis and relay catalysis, which are accomplished by employing
a combination of metal complexes and chiral phosphoric acids.
PMID- 25116833
TI - A new 1,2-ethanedione benzofurane derivative from Tephrosia purpurea.
AB - A new 1,2-ethanedione benzofurane derivative, purpdione (1), was isolated from
Tephrosia purpurea, together with seven known flavonoids, purpurenone (2),
pongamol (3), ovalitenin A (4), karanjin (5), lanceolatin B (6), tachrosin (7)
and villosinol (8). The new structure was elucidated based on the analysis of its
spectroscopic data. The structures of the known compounds were identified by
comparing their spectroscopic data with those reported in the literature. The
isolates exhibited marginal ability to inhibit the settlement of barnacle
(Balanus reticulatus).
PMID- 25116834
TI - Testing the accuracy of an observation-based classifier for rapid detection of
autism risk.
AB - Current approaches for diagnosing autism have high diagnostic validity but are
time consuming and can contribute to delays in arriving at an official diagnosis.
In a pilot study, we used machine learning to derive a classifier that
represented a 72% reduction in length from the gold-standard Autism Diagnostic
Observation Schedule-Generic (ADOS-G), while retaining >97% statistical accuracy.
The pilot study focused on a relatively small sample of children with and without
autism. The present study sought to further test the accuracy of the classifier
(termed the observation-based classifier (OBC)) on an independent sample of 2616
children scored using ADOS from five data repositories and including both
spectrum (n=2333) and non-spectrum (n=283) individuals. We tested OBC outcomes
against the outcomes provided by the original and current ADOS algorithms, the
best estimate clinical diagnosis, and the comparison score severity metric
associated with ADOS-2. The OBC was significantly correlated with the ADOS-G (r=
0.814) and ADOS-2 (r=-0.779) and exhibited >97% sensitivity and >77% specificity
in comparison to both ADOS algorithm scores. The correspondence to the best
estimate clinical diagnosis was also high (accuracy=96.8%), with sensitivity of
97.1% and specificity of 83.3%. The correlation between the OBC score and the
comparison score was significant (r=-0.628), suggesting that the OBC provides
both a classification as well as a measure of severity of the phenotype. These
results further demonstrate the accuracy of the OBC and suggest that reductions
in the process of detecting and monitoring autism are possible.
PMID- 25116837
TI - Anion-pi interactions and positive electrostatic potentials of N-heterocycles
arise from the positions of the nuclei, not changes in the pi-electron
distribution.
AB - We show that the positive electrostatic potentials and molecular quadrupole
moments characteristic of pi-acidic azines, which underlie the ability of these
rings to bind anions above their centres, arise from the position of nuclear
charges, not changes in the pi-electron density distribution.
PMID- 25116836
TI - Associations between past bullying experiences and psychosocial and academic
functioning among college students.
AB - OBJECTIVES: This study examined whether childhood bullying victimization was
associated with psychosocial and academic functioning at college. PARTICIPANTS:
The sample consisted of 413 first-year students from a large northeastern
university. METHODS: Students completed an online survey in February 2012 that
included items assessing past bullying involvement, current psychosocial and
academic functioning, and victimization experiences since arriving at college.
RESULTS: Regression analyses indicated that reports of past bullying and other
peer victimization were associated with lower mental health functioning and
perceptions of physical and mental health, but were not associated with
perceptions of social life at college, overall college experience, or academic
performance. CONCLUSIONS: Childhood bullying victimization is associated with
poorer mental and physical health among first-year college students. Colleges
should consider assessing histories of bullying victimization, along with other
past victimization exposures, in their service provision to students.
PMID- 25116835
TI - Plasma DYRK1A as a novel risk factor for Alzheimer's disease.
AB - To determine whether apparent involvement of DYRK1A in Alzheimer's disease (AD)
pathology makes it a candidate plasma biomarker for diagnosis, we developed a
method to quantify plasma DYRK1A by immunoblot in transgenic mouse models having
different gene dosages of Dyrk1a, and, consequently, different relative protein
expression. Then, we measured plasma DYRK1A levels in 26 patients with
biologically confirmed AD and 25 controls (negative amyloid imaging available on
13). DYRK1A was detected in transgenic mouse brain and plasma samples, and
relative levels of DYRK1A correlated with the gene copy number. In plasma from AD
patients, DYRK1A levels were significantly lower compared with controls
(P<0.0001). Results were similar when we compared AD patients with the subgroup
of controls confirmed by negative amyloid imaging. In a subgroup of patients with
early AD (CDR=0.5), lower DYRK1A expression was confirmed. In contrast, no
difference was found in levels of DYRK1B, the closest relative of DYRK1A, between
AD patients and controls. Further, AD patients exhibited a positive correlation
between plasma DYRK1A levels and cerebrospinal fluid tau and phosphorylated-tau
proteins, but no correlation with amyloid-beta42 levels and Pittsburgh compound B
cortical binding. DYRK1A levels detected in lymphoblastoid cell lines from AD
patients were also lower when compared with cells from age-matched controls.
These findings suggest that reduced DYRK1A expression might be a novel plasma
risk factor for AD.
PMID- 25116838
TI - Identification of agr-positive methicillin-resistant Staphylococcus aureus
harbouring the class A mec complex by MALDI-TOF mass spectrometry.
AB - A small peptide called PSM-mec is encoded on the type II, III and VIII SCCmec
cassettes present in the genomes of nosocomial methicillin-resistant
Staphylococcus aureus (MRSA) strains. This peptide is excreted by agr-positive
strains, which represent about 89% of the strains of our collection and can be
identified by the presence of delta toxin in mass spectrometry. The presence of
the peptide in the MALDI-TOF MS spectra of whole cells was proved by a knock-down
experiment employing a clone that expressed antisense RNA to psm-mec.
Furthermore, evaluation of a collection of clinical agr-positive MRSA and MSSA
isolates and type strains showed that, using a detection window of m/z 2411-2419,
the PSM-mec is detected by mass spectrometry of whole cells with a sensitivity of
0.95 and a specificity of 1, thereby enabling rapid identification of a subgroup
of MRSA with a method that is used during routine identification procedures.
PMID- 25116840
TI - Structural protein-ligand interaction fingerprints (SPLIF) for structure-based
virtual screening: method and benchmark study.
AB - Accurate and affordable assessment of ligand-protein affinity for structure-based
virtual screening (SB-VS) is a standing challenge. Hence, empirical postdocking
filters making use of various types of structure-activity information may prove
useful. Here, we introduce one such filter based upon three-dimensional
structural protein-ligand interaction fingerprints (SPLIF). SPLIF permits
quantitative assessment of whether a docking pose interacts with the protein
target similarly to a known ligand and rescues active compounds penalized by poor
initial docking scores. An extensive benchmark study on 10 diverse data sets
selected from the DUD-E database has been performed in order to evaluate the
absolute and relative efficiency of this method. SPLIF demonstrated an overall
better performance than relevant standard methods.
PMID- 25116841
TI - Alison Jolly: a supremely social intelligence (1937-2014).
PMID- 25116842
TI - The emergence of the Acheulean in East Africa--international workshop, Rome, "La
Sapienza" University, September 12-13, 2013.
PMID- 25116839
TI - Whole genome sequencing indicates Corynebacterium jeikeium comprises 4 separate
genomospecies and identifies a dominant genomospecies among clinical isolates.
AB - Corynebacterium jeikeium is an opportunistic pathogen which has been noted for
significant genomic diversity. The population structure within this species
remains poorly understood. Here, we explore the relationships among 15 clinical
isolates of C. jeikeium (reference strains K411 and ATCC 43734, and 13 primary
isolates collected over a period of 7 years) through genetic, genomic, and
phenotypic studies. We report a high degree of divergence among strains based on
16S ribosomal RNA (rRNA) gene and rpoB gene sequence analysis, supporting the
presence of genetically distinct subgroups. Whole genome sequencing indicates
genomic-level dissimilarity among subgroups, which qualify as four separate and
distinct Corynebacterium species based on an average nucleotide identity (ANIb)
threshold of <95%. Functional distinctions in antibiotic susceptibilities and
metabolic profiles characterize two of these genomospecies, allowing their
differentiation from others through routine laboratory testing. The remaining
genomospecies can be classified through a biphasic approach integrating
phenotypic testing and rpoB gene sequencing. The genomospecies predominantly
recovered from patient specimens does not include either of the existing C.
jeikeium reference strains, implying that studies of this pathogen would benefit
from examination of representatives from the primary disease-causing group. The
clinically dominant genomospecies also has the smallest genome size and gene
repertoire, suggesting the possibility of increased virulence relative to the
other genomospecies. The ability to classify isolates to one of the four C.
jeikeium genomospecies in a clinical context provides diagnostic information for
tailoring antimicrobial therapy and may aid in identification of species-specific
disease associations.
PMID- 25116843
TI - On the cutting edge: new methods and theory for analyzing stone tools.
PMID- 25116844
TI - Catastrophes in evolution: is Cuvier's world extinct or extant?
PMID- 25116845
TI - In the eye (and ears) of the beholder: receiver psychology and human signal
design.
AB - Although the study of signals has been part of human behavioral ecology since the
field's inception,(1) only recently has signaling theory become important to the
evolutionary study of human behavior and culture.(2) Signaling theory's rise to
prominence has been propelled mainly by applications of costly signaling
theory,(3) which has shed light on a wide variety of human behaviors ranging from
hunting(4) to religion.(5,6) Costly signaling rests on the idea that wasteful but
highly visible traits and behaviors can be explained as honest indicators of
underlying qualities that are otherwise difficult to detect. For example, a
laborious hunting technique may serve as a display of skill on the part of the
hunter, who may then be favorably perceived by potential mates and allies.(4) The
costs of the activity ensure that the signal is honest, since unskilled hunters
will not be able to perform as well. Despite the usefulness of this perspective,
many such studies begin by documenting a costly behavior that is then explained
with reference to costly signaling theory. Because such behaviors are easy to
detect, they may be overemphasized in the literature.(7) Moreover, costly
signaling theory by itself can explain neither all signals nor all aspects of
signal design. In this review, we argue that a focus on the role that the
psychology of the intended receiver plays in signal design can expand the scope
of signaling theory as a promising avenue to explain human behavior.
PMID- 25116846
TI - Applying socioendocrinology to evolutionary models: fatherhood and physiology.
AB - Owing to humans' unique life history pattern, particularly comparatively short
interbirth intervals, early weaning, and prolonged support of multiple
dependents, human females have greater reproductive value and higher lifetime
fertility, on average, than do their Great Ape counterparts. As hominin females
began weaning their young early and "stacking" dependents of various ages, they
must have had cooperative allomaternal care partners already in place or been
successful at concurrently soliciting help to ensure a high rate of survival of
their offspring. Following Hrdy, I define allomaternal care (and its derivatives,
such as "allomothers" and "allomothering") as "care from anyone other than the
mother," which thus encompasses a wide range of individuals, including fathers.
Who the likely allomother candidates mothers were and what form that cooperation
took remain intriguing, difficult-to-answer questions, which are limited, in some
capacity, by the lines of evidence available to us. Here, I present a framework
for the ways in which we can integrate neurobiological-endocrine and social
behavioral data ("socioendocrinology") to contribute to this dialogue in terms of
evaluating fathers' roles.
PMID- 25116847
TI - Best practices for reporting on heterogeneous photocatalysis.
PMID- 25116848
TI - Cocoa bioactive compounds: significance and potential for the maintenance of skin
health.
AB - Cocoa has a rich history in human use. Skin is prone to the development of
several diseases, and the mechanisms in the pathogenesis of aged skin are still
poorly understood. However, a growing body of evidence from clinical and bench
research has begun to provide scientific validation for the use of cocoa-derived
phytochemicals as an effective approach for skin protection. Although the
specific molecular and cellular mechanisms of the beneficial actions of cocoa
phytochemicals remain to be elucidated, this review will provide an overview of
the current literature emphasizing potential cytoprotective pathways modulated by
cocoa and its polyphenolic components. Moreover, we will summarize in vivo
studies showing that bioactive compounds of cocoa may have a positive impact on
skin health.
PMID- 25116850
TI - Aggression and social experience: genetic analysis of visual circuit activity in
the control of aggressiveness in Drosophila.
AB - BACKGROUND: Animal aggressiveness is controlled by genetic and environmental
factors. Among environmental factors, social experience plays an important role
in modulating aggression in vertebrates and invertebrates. In Drosophila,
pheromonal activation of olfactory neurons contributes to social suppression of
aggression. While it was reported that impairment in vision decreases the level
of aggression in Drosophila, it remains unknown if visual perception also
contributes to the modulation of aggression by social experience. RESULTS: In
this study, we investigate the role of visual perception in the control of
aggression in Drosophila. We took several genetic approaches to examine the
effects of blocking visual circuit activity on fly aggressive behaviors. In wild
type, group housing greatly suppresses aggressiveness. Loss of vision by mutating
the ninaB gene does not affect social suppression of fly aggression. Similar
suppression of aggressiveness by group housing is observed in fly mutants
carrying a mutation in the eya gene leading to complete loss of eye. Chronic
visual loss does not affect the level of aggressiveness of single-housed flies
that lack social experience prior to behavioral tests. When visual circuit
activity is acutely blocked during behavioral test, however, single-housed flies
display higher levels of aggressiveness than that of control flies. CONCLUSION:
Visual perception does not play a major role in social suppression of aggression
in Drosophila. For single-housed individuals lacking social experience prior to
behavioral tests, visual perception decreases the level of aggressiveness.
PMID- 25116852
TI - Air-stable solid aryl and heteroaryl organozinc pivalates: syntheses and
applications in organic synthesis.
AB - A wide range of air-stable, solid, polyfunctional aryl and heteroarylzinc
pivalates were efficiently prepared by either magnesium insertion or Hal/Mg
exchange followed by transmetalation with Zn(OPiv)2 (OPiv = pivalate). By
reducing the amount of LiCl the air stability could be significantly enhanced
compared with previously prepared reagents. An alternative route is directed
magnesiation using TMPMgCl?LiCl (TMP = 2,2,6,6-tetramethylpiperidyl) followed by
transmetalation with Zn(OPiv)2 or, for very sensitive substrates, direct
zincation by using TMPZnOPiv. These zinc reagents not only show excellent
stability towards air, but they also undergo a broad range of C-C bond-formation
reactions, such as allylation and carbocupration reactions, as well as addition
to aldehydes and 1,4-addition reactions. Acylation reactions can be performed by
using an excess of TMSCl to overcome side reactions of the omnipresent pivalate
anion.
PMID- 25116853
TI - Creating electrochemical gradients by light: from bio-inspired concepts to
photoelectric conversion.
AB - Light is harvested by natural photosynthetic systems to generate electrochemical
gradients that power various reactions. Implementing nature's lessons in
photosynthesis holds great promise for technological advances. With a focus on
designs and concepts, recent progress in generating electrochemical gradients by
light, mimicking the two general types of photosynthetic centers in nature that
make use of either light-induced charge separation or photo-isomerization are
summarized here. Light induced electrochemical gradients pave new ways for
photoelectric conversion. While extensive research in this direction has focused
on light-induced charge separation, recent work has shown that energy conversion
based on photo-isomerization is very promising. Photoswitchable compounds have
been found in nature, such as the retinal molecule in bacteriorhodopsin. These
compounds may form an attractive molecular basis for future progress in this
field.
PMID- 25116854
TI - Interferon-alpha-induced depression: A reply to the letters to the editor by
Mahajan et al. and Porcelli et al.
PMID- 25116851
TI - Emerin expression in well differentiated epithelial lesions of thyroid:
implications in papillary thyroid carcinoma diagnosis and predicting malignant
behavior.
AB - Recently, it has been reported that identifying nuclear membrane irregularities
with anti-emerin antibody is useful for papillary thyroid carcinoma diagnosis.
However, literature regarding the significance of emerin immunohistochemistry in
thyroid is limited. We evaluated the diagnostic accuracy of the well-established
nuclear alterations, nuclear protrusions and recently described nuclear shapes
(garlands and star-like shapes) with emerin immunohistochemistry and hematoxylin-
eosin stain in thyroid lesions. We further evaluated the diagnostic accuracy
measures of tissue microarrays evaluated with both stains, to detect whether
emerin immunohistochemistry improves the diagnostic accuracy for papillary
thyroid carcinoma. For papillary thyroid carcinoma, pseudo- inclusions were best
performers with emerin (diagnostic accuracy: 0.91), whereas with hematoxylin-
eosin diagnostic accuracy of grooves was the highest (0.92). For follicular
variant of papillary thyroid carcinoma, with both stains, predominately oval
nuclear shape had the best diagnostic performance (diagnostic accuracy: 0.95).
Nuclear protrusions were poor identifiers for papillary thyroid carcinoma.
However, with emerin immunohistochemistry, they could successfully identify
malignancy in 83% of the cases. Using emerin immunohistochemistry, in addition to
hematoxylin- eosin improved the diagnostic accuracy for papillary thyroid
carcinoma when compared to hematoxylin- eosin evaluation only (sensitivity: 0.70
vs 0.86, negative predictive value: 0.81 vs. 0.94, diagnostic accuracy: 0.87 vs.
0.94). Consistent with the previous literature, our findings indicate that emerin
immunohistochemistry may be used as an adjunct diagnostic method to identify
papillary thyroid carcinoma. Additionally, we suggest that nuclear protrusions
detected with emerin imunohistochemistry may be used as indicators of malignant
behavior in small tissue samples of thyroid.
PMID- 25116856
TI - Selenoproteins and selenium status in bone physiology and pathology.
AB - BACKGROUND: Emerging evidence supports the view that selenoproteins are essential
for maintaining bone health. SCOPE OF REVIEW: The current state of knowledge
concerning selenoproteins and Se status in bone physiology and pathology is
summarized. MAJOR CONCLUSIONS: Antioxidant selenoproteins including glutathione
peroxidase (GPx) and thioredoxin reductase (TrxR), as a whole, play a pivotal
role in maintaining bone homeostasis and protecting against bone loss. GPx1, a
major antioxidant enzyme in osteoclasts, is up-regulated by estrogen, an
endogenous inhibitor of osteoclastogenesis. TrxR1 is an immediate early gene in
response to 1alpha,25-dihydroxyvitamin D3, an osteoblastic differentiation agent.
The combination of 1alpha,25-dihydroxyvitamin D3 and Se generates a synergistic
elevation of TrxR activity in Se-deficient osteoblasts. Of particular concern,
pleiotropic TrxR1 is implicated in promoting NFkappaB activation. Coincidentally,
TrxR inhibitors such as curcumin and gold compounds exhibit potent
osteoclastogenesis inhibitory activity. Studies in patients with the mutations of
selenocysteine insertion sequence-binding protein 2, a key trans-acting factor
for the co-translational insertion of selenocysteine into selenoproteins have
clearly established a causal link of selenoproteins in bone development. Se
transport to bone relies on selenoprotein P. Plasma selenoprotein P
concentrations have been found to be positively correlated with bone mineral
density in elderly women. GENERAL SIGNIFICANCE: A full understanding of the role
and function of selenoproteins and Se status on bone physiology and pathology may
lead to effectively prevent against or modify bone diseases by using Se.
PMID- 25116857
TI - Expression, regulation and function of human metallothioneins in endothelial
cells.
AB - Metallothioneins (MTs) are small cysteine-rich proteins which are involved in
e.g. metal homeostasis, metal detoxification and protection against oxidative
stress. In addition, several MTs have been shown to regulate expression of
proangiogenic growth factors like vascular endothelial growth factor. Detailed
information about the expression and regulation of specific MT isoforms in
endothelial cells (EC) is limited. We therefore performed extensive mRNA
expression profiling of all known human MTs in EC. We found that the basal
endothelial expression is restricted to MT1E, MT1X, MT2A, and MT3. Physiological
activation of EC by exposure to serum increased the expression of MT1E and MT2A
and induced the expression of MT1M. Furthermore, exposure to zinc or copper
induced the expression of most MT1 isoforms, while hypoxia specifically increased
the expression of MT1E, MT1M, MT1X, and MT3. Finally, knockdown of the dominant
MT isoform in EC, i.e. MT2A, resulted in decreased proliferation and sprouting as
well as in increased migration of human umbilical vein EC. Together, these
findings provide a link between MTs and angiogenesis.
PMID- 25116855
TI - Redox-dependent lipoylation of mitochondrial proteins in Plasmodium falciparum.
AB - Lipoate scavenging from the human host is essential for malaria parasite
survival. Scavenged lipoate is covalently attached to three parasite proteins:
the H-protein and the E2 subunits of branched chain amino acid dehydrogenase
(BCDH) and alpha-ketoglutarate dehydrogenase (KDH). We show mitochondrial
localization for the E2 subunits of BCDH and KDH, similar to previously localized
H-protein, demonstrating that all three lipoylated proteins reside in the
parasite mitochondrion. The lipoate ligase 1, LipL1, has been shown to reside in
the mitochondrion and it catalyses the lipoylation of the H-protein; however, we
show that LipL1 alone cannot lipoylate BCDH or KDH. A second mitochondrial
protein with homology to lipoate ligases, LipL2, does not show ligase activity
and is not capable of lipoylating any of the mitochondrial substrates. Instead,
BCDH and KDH are lipoylated through a novel mechanism requiring both LipL1 and
LipL2. This mechanism is sensitive to redox conditions where BCDH and KDH are
exclusively lipoylated under strong reducing conditions in contrast to the H
protein which is preferentially lipoylated under less reducing conditions. Thus,
malaria parasites contain two different routes of mitochondrial lipoylation, an
arrangement that has not been described for any other organism.
PMID- 25116859
TI - Nucleophilic bromodifluoromethylation of iminium ions.
AB - A method for bromodifluoromethylation of iminium ions using Me3SiCF2Br is
described. The reaction involves room temperature activation of the silicon
reagent by HMPA to generate difluorocarbene, which upon interacting with excess
of bromide ion provides bromodifluoromethyl carbanionic species. The iminium
electrophiles are generated in situ from aldehydes, secondary amines, proton
sponge, and silyl triflate. The reaction can be extended for introduction of
chlorodifluoromethyl and iododifluoromethyl groups.
PMID- 25116858
TI - Effects of galactosylation in immunoglobulin G from all-atom molecular dynamics
simulations.
AB - Explicit water atomistic molecular dynamics simulations (200 ns, ~330,000 atoms)
were performed to study the effects of galactosylation in the Fc domain of
immunoglobulin G1. Two glycoforms were simulated to observe changes in protein
carbohydrate interactions and carbohydrate structure. A high degree of
flexibility was observed in the small hinge region of the protein, while large
domains remained stable. The hinge region flexibility allowed both translation
and rotation of the domains relative to each other, resulting in a large number
of possible conformations available. The distributions of rotational orientations
between the Fab1 and Fab2 domains showed that while these domains are able to
orient themselves rather freely pointing in space they rotated in unison to
remain rotationally oriented at specific angles. Additionally, removing specific
terminal galactose residues increased the mobility of the carbohydrate, resulting
in different protein-carbohydrate interactions. Glycosylation has been suggested
as a route to improve the aggregation resistance of monoclonal antibodies for
therapeutic treatments to aid the immune system. The results presented here may
provide insight into the search for IgG molecules with increased aggregation
resistance to be used as monoclonal antibodies.
PMID- 25116860
TI - Antioxidant activity and chemical composition of three Tunisian Cistus: Cistus
monspeliensis, Cistus villosus and Cistus libanotis.
AB - The chemical composition of three rockrose Cistus species, Cistus monspeliensis,
Cistus libanotis and Cistus villosus, collected in Tunisia, was studied by HPTLC,
focusing on the terpenes and phenols constituents. Diterpenes of Cistus are
important as the main constituents of the leaf sticky aromatic resin, known as
labdanum, which are highly appreciated in perfumery. Polyphenols in the
methanolic extracts of each species were identified, quantified as total and as
flavonoids and tannins, and tested for antioxidant activity. Diterpenes were
evident in C. libanotis and C. monspeliensis, whereas they were practically
absent in C. villosus; C. libanotis had higher phenolic amount, whereas
antioxidant activities were important, but different according to the following
tests: DPPH radical scavenging, conversion of the Fe(3+/)ferricyanide complex and
inhibition of beta-carotene bleaching. The reported data confirm the validity of
utilisation of Cistus sp. in marketed herbal products, as well as the relevant
presence of diterpenes in species actually not used for labdanum production.
PMID- 25116861
TI - Immunological effects of massage after exercise: A systematic review.
AB - OBJECTIVE: The objective of this review was to determine whether immune
parameters can be modulated by massage after intense physical activity. METHODS:
A search was conducted in Pub Med Medline, PEDro, and Cochrane databases, using
the key words: "massage", "myofascial release", "acupressure", "recovery", and
"warm up" combined with "exercise", "exercise-induced muscle damage", "sport",
"immunology", and lymphocytes" independently. Only controlled studies published
between 1970 and 2012 were selected, with no restrictions regarding publication
language. The CONSORT Declaration was applied to assess the quality of the
selected studies. RESULTS: The initial search identified 739 publications in the
databases, of which only 5 met the review inclusion criteria. A positive
relationship between immunological recovery and post-exercise massage was
reported by some of these studies but not by others. CONCLUSION: There is
preliminary evidence that massage may modulate immune parameters when applied
after exercise, but more research is needed to confirm this possibility.
PMID- 25116863
TI - The influence of narrative practice techniques on child behaviors in forensic
interviews.
AB - During investigations of child sexual abuse, forensic interviewers must maintain
a delicate balance of providing support for the child while collecting forensic
evidence about the abuse allegation required for credible evidence for court
purposes. The use of narrative practice techniques can achieve both goals by
creating conditions that facilitate the possibility that children will feel safe
enough to provide detailed descriptions of the alleged abuse. This article
reports findings from an evaluation of a change in practice using the CornerHouse
Forensic Interview Protocol in which narrative practice techniques were
incorporated into the interview format. Findings show that children provided more
detailed accounts of abuse when interviewers used open-ended questions and
supportive statements through narrative practice.
PMID- 25116864
TI - Caregiver-youth communication about sex in South Africa: the role of maternal
child sexual abuse history.
AB - Much of the research on child sexual abuse focuses on negative outcomes. This
brief report explores a potentially protective parenting behavior among black
South African female caregivers with and without a child sexual abuse history.
Using cross-sectional baseline data, we hypothesized that caregiver child sexual
abuse history would be positively associated with caregiver-youth sex
communication and this relationship would be strongest for girls. Youth whose
caregiver experienced child sexual abuse were more likely to report communicating
with their caregiver about sex than youth whose caregivers did not experience
child sexual abuse; however, this relation did not hold for caregiver reported
communication. Child sexual abuse survivors' ability and decision to discuss sex
with their youth has the potential to protect youth from sexual risk and
demonstrates resilience among a group rarely acknowledged for positive parenting
practices.
PMID- 25116865
TI - How ineffective family environments can compound maldevelopment of critical
thinking skills in childhood abuse survivors.
AB - The high stress of childhood abuse is associated with neurobiological detriments
to executive function. Child abuse survivors may also be cognitively and
relationally disadvantaged as a result of being raised in emotionally
impoverished families that lack cohesion, organization, flexibility, self
expression, and moral and ethical values and fail to provide opportunities for
effective learning. A review of literature demonstrates how dysfunctional family
of origin environments common to child abuse survivors, concomitant with the
extreme stress of overt acts of abuse, can act as a barrier to the development of
higher-order critical thinking skills. The article concludes by discussing
ramifications of critical thinking skill deficits in child abuse survivors and
highlights the importance of integrating and prioritizing critical thinking
skills training in treatment.
PMID- 25116862
TI - Structural and functional connectivity of the human brain in autism spectrum
disorders and attention-deficit/hyperactivity disorder: A rich club-organization
study.
AB - Attention-deficit/hyperactive disorder (ADHD) and autism spectrum disorders (ASD)
are two of the most common and vexing neurodevelopmental disorders among
children. Although the two disorders share many behavioral and neuropsychological
characteristics, most MRI studies examine only one of the disorders at a time.
Using graph theory combined with structural and functional connectivity, we
examined the large-scale network organization among three groups of children: a
group with ADHD (8-12 years, n = 20), a group with ASD (7-13 years, n = 16), and
typically developing controls (TD) (8-12 years, n = 20). We apply the concept of
the rich-club organization, whereby central, highly connected hub regions are
also highly connected to themselves. We examine the brain into two different
network domains: (1) inside a rich-club network phenomena and (2) outside a rich
club network phenomena. The ASD and ADHD groups had markedly different patterns
of rich club and non rich-club connections in both functional and structural
data. The ASD group exhibited higher connectivity in structural and functional
networks but only inside the rich-club networks. These findings were replicated
using the autism brain imaging data exchange dataset with ASD (n = 85) and TD (n
= 101). The ADHD group exhibited a lower generalized fractional anisotropy and
functional connectivity inside the rich-club networks, but a higher number of
axonal fibers and correlation coefficient values outside the rich club. Despite
some shared biological features and frequent comorbity, these data suggest ADHD
and ASD exhibit distinct large-scale connectivity patterns in middle childhood.
PMID- 25116866
TI - Perpetration, revictimization, and self-injury: traumatic reenactments of child
sexual abuse in a nonclinical sample of South African adolescents.
AB - Risk factors for traumatic reenactments of child sexual abuse experiences
(perpetration, revictimization, and self-injury) were examined in a sample of 718
South African secondary school adolescents. Logistic regression analyses
indicated that the most consistent predictors of reenactments were a history of
child sexual abuse (rape and/or indecent assault) and respondents' gender, with
males being significantly more likely than females to report perpetration (OR =
13.5) and females being more likely to report revictimization (OR = 3.2) and self
injury (OR = 2.5). An analysis restricted to respondents with a history of child
sexual abuse indicated that negative abuse-related cognitions were the most
consistent predictor of all forms of traumatic reenactment.
PMID- 25116868
TI - Thermally activated polymorphic transition from a 1D ribbon to a 2D carpet:
squaric acid on Au(111).
AB - Polymorphic transition from the 1D ribbon to the 2D carpet superstructure of
squaric acid molecules on Au(111) was achieved through a thermally activated
process. Our combined STM and DFT study revealed that the molecular arrangements
in 1D and 2D superstructures are determined by the stability of their
conformational isomers and assembled structures, respectively.
PMID- 25116867
TI - Small-size circulating endothelial microparticles in coronary artery disease.
AB - OBJECTIVES: Several recent lines of evidence indicate that endothelial
microparticles are a new biomarker that can be used to monitor endothelial
dysfunction in coronary artery disease (CAD). However, data concerning the
detection of small microparticles (diameter <0.5 um) are lacking. The aim of this
study was to detect small-size endothelial microparticles (SEMPs) in CAD patients
to monitor endothelial dysfunction. METHODS: In total, 19 CAD patients and 14
healthy subjects were recruited. The absolute numbers and percentages of
CD31(+)/CD42b- SEMPs and CD62E(+) SEMPs were determined by flow cytometry.
Clinical parameters were also recorded. RESULTS: The mean percentage of CD62E(+)
SEMPs was higher in the CAD patient group than in the healthy subject group. The
area under the receiver operating characteristic curve of the percentage of
CD62E(+) SEMPs was 0.795, and the cut-off value was 1.35. There was no
correlation between the percentage of CD62E(+) SEMPs and various clinical
parameters. CONCLUSION: The percentage of CD62E(+) SEMPs is a potential biomarker
for monitoring endothelial function in CAD.
PMID- 25116869
TI - Widening and high inclination of the middle cerebral artery bifurcation are
associated with presence of aneurysms.
AB - BACKGROUND AND PURPOSE: The middle cerebral artery (MCA) bifurcation is a
preferred site for aneurysm formation. Wider bifurcation angles have been
correlated with increased risk of aneurysm formation. We hypothesized a link
between the presence of MCA aneurysms and the angle morphology of the
bifurcation. METHODS: Three-dimensional rotational angiography volumes of 146 MCA
bifurcations (62 aneurysmal) were evaluated for angle morphology: parent-daughter
angles (larger daughter F1, smaller daughter F2), bifurcation angle (F1+F2), and
inclination angle (gamma) between the parent vessel axis and the plane determined
by daughter vessel axes. Statistics were evaluated using Wilcoxon rank-sum
analysis and area under the receiver operator characteristic curve. RESULTS:
Aneurysmal bifurcations had wider inclination angle gamma (median 57.8 degrees
versus 15.4 degrees ; P<0.0001). Seventy-five percent of aneurysmal MCAs had
gamma >10 degrees , compared with 25% nonaneurysmal. F1 and F2, but especially
F1+F2, were significantly larger in aneurysmal bifurcations (median 171.3 degrees
versus 98.1 degrees ; P<0.0001). Sixty-seven percent of aneurysmal bifurcations
had F1+F2 >161 degrees , compared with 0% nonaneurysmal MCAs. An optimal
threshold of 140 degrees was established for F1+F2 (area under the curve, 0.98).
Sixty-eight percent of aneurysms originated off the daughter branches. Seventy
six percent of them originated off the branch with the largest branching angle,
specifically if this was the smaller daughter branch. Wider F1+F2 correlated with
aneurysm neck width, but not dome size. CONCLUSIONS: MCA bifurcations harboring
aneurysms have significantly larger branching angles and more often originate off
the branch with the largest angle. Wider inclination angle is strongly correlated
with aneurysm presence, a novel finding. The results point to altered wall shear
stress regulation as a possible factor in aneurysm development and progression.
PMID- 25116870
TI - Effects of surgical revascularization on cerebral oxygen metabolism in patients
with Moyamoya disease: an 15O-gas positron emission tomographic study.
AB - BACKGROUND AND PURPOSE: This prospective study was aimed to evaluate the effects
of surgical revascularization on cerebral oxygen metabolism in moyamoya disease.
METHODS: This study included totally 69 hemispheres of 42 patients who underwent
superficial temporal artery to middle cerebral artery anastomosis and indirect
bypass for moyamoya disease between 2000 and 2011. There were 12 children and 30
adults. MRI and (15)O-gas positron emission tomography were performed before and
3 to 4 months after surgery. Hemodynamic and metabolic parameters were precisely
quantified and statistically analyzed. RESULTS: Preoperative positron emission
tomographic scans revealed that cerebral blood flow was decreased, cerebral blood
volume was increased, and cerebral metabolic rate for oxygen was decreased in
both pediatric and adult patients. Cerebral metabolic rate for oxygen reduction
was observed in ~80% of pediatric (16/21; 76%) and adult hemispheres (38/48;
79%). Surgical revascularization resolved hemodynamic compromise in all operated
hemispheres. Cerebral metabolic rate for oxygen significantly improved in
pediatric patients without parenchymal lesions (n=8), but not those with
parenchymal lesions (n=8). Multivariate analysis revealed that cerebral metabolic
rate for oxygen significantly improved in younger adult patients without
parenchymal lesions (P=0.0264; odds ratio, 0.88; 95% confidence interval, 0.79
0.99). CONCLUSIONS: Cerebral oxygen metabolism is significantly depressed in ~80%
of the involved hemispheres of moyamoya disease and improves in pediatric and
younger adult patients without parenchymal lesions after bypass surgery. Cerebral
oxygen metabolism may be reversibly depressed in response to cerebral ischemia in
them although the underlying mechanisms are still unclear.
PMID- 25116871
TI - When you are old.
PMID- 25116872
TI - Ethical approach to surrogate consent for hemicraniectomy in older patients with
extensive middle cerebral artery stroke.
PMID- 25116873
TI - Letter by Shang regarding article, "Relative contributions of sympathetic,
cholinergic, and myogenic mechanisms to cerebral autoregulation".
PMID- 25116875
TI - Report from the European Stroke Organization 2014.
PMID- 25116874
TI - Plasma magnesium and risk of ischemic stroke among women.
AB - BACKGROUND AND PURPOSE: Lower plasma magnesium levels may be associated with
higher blood pressure and endothelial dysfunction, but sparse prospective data
are available for stroke. METHODS: Among 32,826 participants in the Nurses'
Health Study who provided blood samples in 1989 to 1990, incident ischemic
strokes were identified and confirmed by medical records through 2006. We
conducted a nested case-control analysis of 459 cases, matched 1:1 to controls on
age, race/ethnicity, smoking status, date of blood draw, fasting status,
menopausal status, and hormone use. We used conditional logistic regression
models to estimate the multivariable adjusted association of plasma magnesium and
the risk of ischemic stroke and ischemic stroke subtypes. RESULTS: Median
magnesium levels did not differ between ischemic stroke cases and controls
(median, 0.86 mmol/L for both; P=0.14). Conditional on matching factors, women in
the lowest magnesium quintile had a relative risk of 1.34 (95% confidence
interval, 0.86-2.10; P trend=0.13) for total ischemic stroke compared with women
in the highest quintile. Additional adjustment for risk factors and confounders
did not substantially alter the risk estimates for total ischemic stroke. Women
with magnesium levels<0.82 mmol/L had significantly greater risk of total
ischemic stroke (multivariable relative risk, 1.57; 95% confidence interval, 1.09
2.27; P=0.01) and thrombotic stroke (multivariable relative risk, 1.66; 95%
confidence interval, 1.03-2.65; P=0.03) compared with women with magnesium
levels>=0.82 mmol/L. No significant effect modification was observed by age, body
mass index, hypertension, or diabetes mellitus. CONCLUSIONS: Lower plasma
magnesium levels may contribute to higher risk of ischemic stroke among women.
PMID- 25116876
TI - Coronary artery calcification, intima-media thickness, and ankle-brachial index
are complementary stroke predictors.
AB - BACKGROUND AND PURPOSE: Coronary artery calcification (CAC), a marker of coronary
atherosclerosis, predicts stroke in addition to established risk factors. Whether
CAC's predictive value can be improved by peripheral atherosclerosis markers,
namely carotid intima-media thickness (CIMT) and ankle-brachial index (ABI), was
unknown. METHODS: A total of 3289 participants of the population-based Heinz
Nixdorf Recall study (45-75 years; 48.8% men) without previous stroke or coronary
heart disease were evaluated for incident stroke for 9.0+/-1.9 years. CAC, CIMT,
and ABI were examined as stroke predictors. RESULTS: Eighty-four strokes occurred
during follow-up. In multivariable Cox proportional hazard regressions, CAC
(hazard ratio, 1.45 [95% confidence interval, 1.11-1.88] per SD increase in
ln(CAC+1); SD, 2.40), CIMT (1.34 [1.08-1.66] per SD increase; SD, 0.127 mm), and
ABI (1.55 [1.32-1.82] per SD decrease; SD, 0.148) were associated with stroke in
addition to established risk factors. When combined with each other, ln(CAC+1)'s
hazard ratio remained similar when CIMT (1.41 [1.09-1.83]) was inserted into the
multivariable model, but slightly decreased when ABI (1.31 [1.01-1.72]) or CIMT
and ABI (1.29 [0.99-1.68]) were included. Although CAC alone did not
significantly elevate the area under the curve in Harrell's c-statistics (by
0.009; P=0.379) in addition to established risk factors, the combination of CAC
and ABI increased area under the curve (by 0.029; P=0.047), as did ABI (by 0.025;
P=0.038) but not CIMT (by 0.002; P=0.795) alone. The combination of CAC and ABI
also resulted in significant category-free net reclassification and integrated
discrimination improvement. CONCLUSIONS: CAC, CIMT, and ABI provide complementary
information about stroke risk. ABI, which is distinctive in a small
subpopulation, had the highest and CIMT, which is distributed across a larger
range of values, had the lowest predictive value.
PMID- 25116877
TI - Features of cerebral autosomal recessive arteriopathy with subcortical infarcts
and leukoencephalopathy.
PMID- 25116879
TI - White matter perivascular spaces are related to cortical superficial siderosis in
cerebral amyloid angiopathy.
AB - BACKGROUND AND PURPOSE: We set out to investigate whether MRI-visible centrum
semiovale perivascular spaces (CSO-PVS), a potential biomarker of impaired
interstitial fluid drainage in sporadic cerebral amyloid angiopathy, is
associated with cortical superficial siderosis (cSS), reflecting recurrent
hemorrhage from severe leptomeningeal and superficial cortical vascular amyloid.
METHODS: Retrospective multicenter cohort study of possible/probable cerebral
amyloid angiopathy according to the Boston criteria. PVS were rated in basal
ganglia and CSO (CSO-PVS) on axial T2-weighted sequences, using a validated 4
point visual rating scale and were classified as high (score>2) or low degree
(score<=2) for prespecified analyses. Independent risk factors for high CSO-PVS
degree were investigated in logistic regression. RESULTS: The final cohort
consisted of 138 cerebral amyloid angiopathy patients (mean age, 71.8 years; 95%
confidence interval, 70.2-73.4 years; 52.2% men). High CSO-PVS degree was present
in 61.2% of cases. The prevalence of any cSS, and disseminated cSS (involving >3
sulci), was higher in patients with high versus low CSO-PVS degree (for any cSS
45.9% versus 13.5%; P<0.00005; for disseminated cSS 31.8% versus 0%; P<0.00005).
In multivariable logistic regression analysis, cSS presence (odds ratio, 4.78;
95% confidence interval, 1.64-13.87; P=0.004) was an independent predictors of
high CSO-PVS degree. We found no associations between basal ganglia PVS and cSS.
CONCLUSIONS: High degree of CSO-PVS is highly prevalent in sporadic cerebral
amyloid angiopathy and is related to cSS. Our findings suggest that severe
leptomeningeal and cortical vascular amyloid (causing cSS) is related to impaired
interstitial fluid drainage from cerebral white matter, although determining the
causal direction of this relationship requires prospective studies.
PMID- 25116880
TI - Evaluation of a patient with spinal cord infarction after a hypotensive episode.
PMID- 25116881
TI - Use of Montreal Cognitive Assessment in patients with stroke.
PMID- 25116878
TI - Associations between estimated glomerular filtration rate and stroke outcomes in
diabetic versus nondiabetic patients.
AB - BACKGROUND AND PURPOSE: Low estimated glomerular filtration rate (eGFR) is known
to be associated with clinical adverse outcomes. However, whether diabetes
mellitus influences the association between eGFR and prognosis of stroke is still
not elucidated. METHODS: Prospective cohort of 17,280 (nondiabetic 12,498 and
diabetic 4782) Chinese patients with acute stroke from the China National Stroke
Registry and from abnormal glucose regulation in patients with acute stroke
across China (ACROSS) between 2007 and 2009 were followed-up for 1 year for all
cause mortality, stroke recurrence, and stroke disability related to baseline
eGFR in the presence and absence of diabetes mellitus. RESULTS: Among nondiabetic
patients, as compared with eGFR of 90 to 119 mL/min per 1.73 m2, the adjusted
odds ratio of lower eGFR of <45 mL/min per 1.73 m2 was 2.79 (95% confidence
interval, 2.09-3.73) for all-cause mortality, 2.28 (1.74-2.98) for stroke
recurrence, and 1.53 (1.16-2.01) for stroke disability; higher eGFR of >=120
mL/min per 1.73 m2 was just significantly associated with higher risk of all
cause mortality (odds ratio, 1.38; 95% confidence interval, 1.02-1.86) but not
with other outcomes. In diabetic patients, the adjusted odds ratios of all-cause
mortality, stroke recurrence, and stroke disability in lower eGFR were 2.16 (1.51
3.08), 1.43 (1.02-2.00), and 1.38 (0.98-1.95), respectively; higher eGFR was
significantly associated with higher risks of all stroke outcomes. CONCLUSIONS:
Decreased eGFR (<45 mL/min per 1.73 m2) is a strong predictor of all-cause
mortality, stroke recurrence, and stroke disability in diabetic and nondiabetic
patients with acute stroke. Increased eGFR (>=120 mL/min per 1.73 m2) is
associated with all of stroke outcomes in diabetic patients and linked to all
cause mortality in nondiabetic patients.
PMID- 25116882
TI - Number of cerebral microbleeds and risk of intracerebral hemorrhage after
intravenous thrombolysis.
AB - BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are found in a substantial
proportion of patients with ischemic stroke eligible for treatment with
intravenous thrombolysis. Until now, there is limited data on the impact of
multiple CMBs on occurrence of intracerebral hemorrhage (ICH) after intravenous
thrombolysis. METHODS: Between 2008 and 2013, all patients receiving MRI-based
intravenous thrombolysis were identified within our prospective thrombolysis
register. Number of CMBs was rated on pretreatment T2*-weighted MRI by a rater
blinded to clinical data and follow-up. Outcomes of interest were occurrence of
symptomatic ICH (sICH) and parenchymal hemorrhage (PH). RESULTS: Among 326
included patients, 52 patients had a single CMB (16.0%), 19 had 2 to 4 CMBs
(5.8%), and 10 had >=5 CMBs (3.1%). Frequency of sICH/PH was 1.2%/5.7% in
patients without CMBs, 3.8%/3.8% in patients with a single CMB, 10.5%/21.1% in
patients with 2 to 4 CMBs, and 30.0%/30.0% in patients with >=5 CMBs,
respectively (each P for trend<0.01). The unadjusted odds ratio per additional
CMB for sICH was 1.19 (95% confidence interval, 1.07-1.33; P<0.01) and for PH was
1.13 (95% confidence interval, 1.03-1.24; P=0.01). Compared with patients without
CMBs, both patients with 2 to 4 CMBs (P=0.02/P=0.02) and patients with >=5 CMBs
(P<0.01/P<0.01) had significantly increased odds ratios for sICH and PH, whereas
in patients with a single CMB, odds ratios were not significantly increased
(P=0.21/P=0.59). The association of CMB burden with sICH/PH remained significant
after adjustment for possible confounders (age, age-related white matter changes
score, atrial fibrillation, onset-to-treatment time, prior statin use, and
systolic blood pressure on admission). CONCLUSIONS: Our findings indicate a
higher risk of sICH and PH after intravenous thrombolysis when multiple CMBs are
present, with a graded relationship to increasing baseline CMB number.
PMID- 25116883
TI - Response to letter regarding article, "Relative contributions of sympathetic,
cholinergic, and myogenic mechanisms to cerebral autoregulation".
PMID- 25116884
TI - Response to letter regarding article, "N-terminal pro-B-type natriuretic peptide
and stroke risk: the Reasons for Geographic and Racial Differences in Stroke
cohort".
PMID- 25116887
TI - The benefits of a 'right-touch' approach to health care regulation.
PMID- 25116885
TI - Encapsulated cells expressing a chemotherapeutic activating enzyme allow the
targeting of subtoxic chemotherapy and are safe and efficacious: data from two
clinical trials in pancreatic cancer.
AB - Despite progress in the treatment of pancreatic cancer, there is still a need for
improved therapies. In this manuscript, we report clinical experience with a new
therapy for the treatment of pancreatic cancer involving the implantation of
encapsulated cells over-expressing a cytochrome P450 enzyme followed by
subsequent low-dose ifosfamide administrations as a means to target activated
ifosfamide to the tumor. The safety and efficacy of the angiographic instillation
of encapsulated allogeneic cells overexpressing cytochrome P450 in combination
with low-dose systemic ifosfamide administration has now been evaluated in 27
patients in total. These patients were successfully treated in four centers by
three different interventional radiologists, arguing strongly that the treatment
can be successfully used in different centers. The safety of the intra-arterial
delivery of the capsules and the lack of evidence that the patients developed an
inflammatory or immune response to the encapsulated cells or encapsulation
material was shown in all 27 patients. The ifosfamide dose of 1 g/m2/day used in
the first trial was well tolerated by all patients. In contrast, the ifosfamide
dose of 2 g/m2/day used in the second trial was poorly tolerated in most
patients. Since the median survival in the first trial was 40 weeks and only 33
weeks in the second trial, this strongly suggests that there is no survival
benefit to increasing the dose of ifosfamide, and indeed, a lower dose is
beneficial for quality of life and the lack of side effects. This is supported by
the one-year survival rate in the first trial being 38%, whilst that in the
second trial was only 23%. However, taking the data from both trials together, a
total of nine of the 27 patients were alive after one year, and two of these nine
patients were alive for two years or more.
PMID- 25116888
TI - Pharmacological consequences of inhaled drug delivery to small airways in the
treatment of asthma.
AB - Small peripheral airways are an important target for the anti-inflammatory
treatment of asthma. To make anti-inflammatory drugs (inhaled corticosteroids
[ICS]) effectively reach small airways, they should be delivered using inhalation
techniques containing high proportions of fine or super-fine particles. Higher
proportions of fine particles are associated with higher systemic absorption of
ICS leading to an increased risk of endogenous cortisol suppression. Ciclesonide,
despite the highest proportion of fine and super-fine particle fractions, is the
only ICS not associated with an increased risk of systemic adverse effects,
including cortisol suppression. In contrary to ICS, bronchodilators should not be
administered to peripheral airways. This does not improve their efficacy and may
increase their risk of cardiotoxicity. Thus, from a pharmacological point of view
and the theory of aerosols' deposition, fixed combinations of ICS and long-acting
beta agonists are always suboptimal. In many cases, the best solution may be to
use fine-particle ciclesonide and a non-fine particle beta agonist administered
from separate inhalers.
PMID- 25116886
TI - Resuscitation speed affects brain injury in a large animal model of traumatic
brain injury and shock.
AB - BACKGROUND: Optimal fluid resuscitation strategy following combined traumatic
brain injury (TBI) and hemorrhagic shock (HS) remain controversial and the effect
of resuscitation infusion speed on outcome is not well known. We have previously
reported that bolus infusion of fresh frozen plasma (FFP) protects the brain
compared with bolus infusion of 0.9% normal saline (NS). We now hypothesize
reducing resuscitation infusion speed through a stepwise infusion speed increment
protocol using either FFP or NS would provide neuroprotection compared with a
high speed resuscitation protocol. METHODS: 23 Yorkshire swine underwent a
protocol of computer controlled TBI and 40% hemorrhage. Animals were left in
shock (mean arterial pressure of 35 mmHg) for two hours prior to resuscitation
with bolus FFP (n = 5, 50 ml/min) or stepwise infusion speed increment FFP (n =
6), bolus NS (n = 5, 165 ml/min) or stepwise infusion speed increment NS (n = 7).
Hemodynamic variables over a 6-hour observation phase were recorded. Following
euthanasia, brains were harvested and lesion size as well as brain swelling was
measured. RESULTS: Bolus FFP resuscitation resulted in greater brain swelling
(22.36 +/- 1.03% vs. 15.58 +/- 2.52%, p = 0.04), but similar lesion size compared
with stepwise resuscitation. This was associated with a lower cardiac output (CO:
4.81 +/- 1.50 l/min vs. 5.45 +/- 1.14 l/min, p = 0.03). In the NS groups, bolus
infusion resulted in both increased brain swelling (37.24 +/- 1.63% vs. 26.74 +/-
1.33%, p = 0.05) as well as lesion size (3285.44 +/- 130.81 mm(3) vs. 2509.41 +/-
297.44 mm3, p = 0.04). This was also associated with decreased cardiac output
(NS: 4.37 +/- 0.12 l/min vs. 6.35 +/- 0.10 l/min, p < 0.01). CONCLUSIONS: In this
clinically relevant model of combined TBI and HS, stepwise resuscitation
protected the brain compared with bolus resuscitation.
PMID- 25116889
TI - Mechanistic studies of Gd3+-based MRI contrast agents for Zn2+ detection: towards
rational design.
AB - A series of novel pyridine-based Gd(3+) complexes have been prepared and studied
as potential MRI contrast agents for Zn(2+) detection. By independent assessment
of molecular parameters affecting relaxivity, we could interpret the relaxivity
changes observed upon Zn(2+) binding in terms of variations of the rotational
motion.
PMID- 25116891
TI - Reliability in psychiatric diagnosis with the DSM: old wine in new barrels.
PMID- 25116890
TI - A bioenergetic basis for membrane divergence in archaea and bacteria.
AB - Membrane bioenergetics are universal, yet the phospholipid membranes of archaea
and bacteria-the deepest branches in the tree of life-are fundamentally
different. This deep divergence in membrane chemistry is reflected in other stark
differences between the two domains, including ion pumping and DNA replication.
We resolve this paradox by considering the energy requirements of the last
universal common ancestor (LUCA). We develop a mathematical model based on the
premise that LUCA depended on natural proton gradients. Our analysis shows that
such gradients can power carbon and energy metabolism, but only in leaky cells
with a proton permeability equivalent to fatty acid vesicles. Membranes with
lower permeability (equivalent to modern phospholipids) collapse free-energy
availability, precluding exploitation of natural gradients. Pumping protons
across leaky membranes offers no advantage, even when permeability is decreased
1,000-fold. We hypothesize that a sodium-proton antiporter (SPAP) provided the
first step towards modern membranes. SPAP increases the free energy available
from natural proton gradients by ~60%, enabling survival in 50-fold lower
gradients, thereby facilitating ecological spread and divergence. Critically,
SPAP also provides a steadily amplifying advantage to proton pumping as membrane
permeability falls, for the first time favoring the evolution of ion-tight
phospholipid membranes. The phospholipids of archaea and bacteria incorporate
different stereoisomers of glycerol phosphate. We conclude that the enzymes
involved took these alternatives by chance in independent populations that had
already evolved distinct ion pumps. Our model offers a quantitatively robust
explanation for why membrane bioenergetics are universal, yet ion pumps and
phospholipid membranes arose later and independently in separate populations. Our
findings elucidate the paradox that archaea and bacteria share DNA transcription,
ribosomal translation, and ATP synthase, yet differ in equally fundamental traits
that depend on the membrane, including DNA replication.
PMID- 25116892
TI - Peromyscus leucopus mice: a potential animal model for haematological studies.
AB - Peromyscus leucopus mice share physical similarities with laboratory mice Mus
musculus (MM) but have higher agility and longer lifespan. We compared
domesticated P. leucopus linville (PLL) and M. musculus C57BL/6 (MMB6) mice for
cellular composition of peripheral blood (PB), bone marrow (BM) and spleen. PLL
mice had significantly fewer platelets and significantly more monocytes in the
blood, and notably fewer megakaryocytes in the BM. Spleens of PLL mice were
significantly smaller, with 50% fewer cells and reduced 'red pulp'. There was no
obvious haematological change in PLL mice between 2-8 and 16-26 months of age,
except for a significant increase in blood monocytes. Cellular reactive oxygen
species (ROS) content showed no change with age but differed significantly
between different cell types. Treating two to eight month-old PLL mice with
antioxidant N-acetylcysteine in drinking water for three months did not affect
cellular ROS content, but increased blood leucocytes especially the concentration
of monocytes. The low platelets, low megakaryocytes, high monocytes and low
splenic erythropoiesis in PLL mice resemble human measurements better than the
values seen in MMB6.
PMID- 25116893
TI - Inhibition of microRNA-125a promotes human endothelial cell proliferation and
viability through an antiapoptotic mechanism.
AB - The microRNA-125a (miR-125a) is highly expressed in endothelial cells, but its
role in vascular biology is not known. Endothelial cell proliferation and
viability play an important role in endothelial healing, and we hypothesize that
miR-125a regulates this process. The aim of the present study was to investigate
if miR-125a controls human endothelial cell proliferation, viability and
endothelial healing, and to assess the mechanisms involved. We showed that
overexpression of miR-125a by transfection with miR-125a mimic reduced human
umbilical vein endothelial cell (HUVEC) proliferation and viability, and
stimulated apoptosis as demonstrated by a miR-125a-induced increase of the
proportion of annexin V-positive cells monitored by flow cytometry. Moreover, we
showed that the miR-125a mimic downregulated the antiapoptotic Bcl2 protein and
upregulated caspase 3, suggesting that these two proteins represent molecular
targets for miR-125a. Accordingly, transfection with miR-125a inhibitor,
downregulating miR-125a expression, promoted HUVEC proliferation and viability,
and reduced apoptosis. Importantly, transfection with miR-125a inhibitor promoted
HUVEC tube formation in Matrigel, suggesting that reduction of miR-125a has a
proangiogenic effect. In conclusion, downregulation of miR-125a through local
transfection with miR-125a inhibitor might be a new way to enhance endothelial
cell proliferation and viability, thereby promoting the reendothelialization
observed in response to intimal injury.
PMID- 25116895
TI - Dispacamide E and other bioactive bromopyrrole alkaloids from two Indonesian
marine sponges of the genus Stylissa.
AB - Chemical investigation of methanolic extracts of the two Indonesian marine
sponges Stylissa massa and Stylissa flabelliformis yielded 25 bromopyrrole
alkaloids including 2 new metabolites. The structures of all isolated compounds
were unambiguously elucidated based on extensive 1D and 2D NMR, LR-MS and HR-MS
analyses. All isolated compounds were assayed for their antiproliferative and
protein kinase inhibitory activities. Several of the tested compounds revealed
selective activity(ies) which suggested preliminary SARs of the isolated
bromopyrrole alkaloids.
PMID- 25116896
TI - Atypical resting synchrony in autism spectrum disorder.
AB - Autism spectrum disorder (ASD) is increasingly understood to be associated with
aberrant functional brain connectivity. Few studies, however, have described such
atypical neural synchrony among specific brain regions. Here, we used
magnetoencephalography (MEG) to characterize alterations in functional
connectivity in adolescents with ASD through source space analysis of phase
synchrony. Resting-state MEG data were collected from 16 adolescents with ASD and
15 age- and sex-matched typically developing (TD) adolescents. Atlas-guided
reconstruction of neural activity at various cortical and subcortical regions was
performed and inter-regional phase synchrony was calculated in physiologically
relevant frequency bands. Using a multilevel approach, we characterized atypical
resting-state synchrony within specific anatomically defined networks as well as
altered network topologies at both regional and whole-network scales. Adolescents
with ASD demonstrated frequency-dependent alterations in inter-regional
functional connectivity. Hyperconnectivity was observed among the frontal,
temporal, and subcortical regions in beta and gamma frequency ranges. In
contrast, parietal and occipital regions were hypoconnected to widespread brain
regions in theta and alpha bands in ASD. Furthermore, we isolated a
hyperconnected network in the gamma band in adolescents with ASD which
encompassed orbitofrontal, subcortical, and temporal regions implicated in social
cognition. Results from graph analyses confirmed that frequency-dependent
alterations of network topologies exist at both global and local levels. We
present the first source-space investigation of oscillatory phase synchrony in
resting-state MEG in ASD. This work provides evidence of atypical connectivity at
physiologically relevant time scales and indicates that alterations of functional
connectivity in adolescents with ASD are frequency dependent and region
dependent.
PMID- 25116897
TI - Contemporary patterns of discharge aspirin dosing after acute myocardial
infarction in the United States: results from the National Cardiovascular Data
Registry (NCDR).
AB - BACKGROUND: Accumulated data suggest that low-dose aspirin after myocardial
infarction (MI) may offer similar efficacy to higher dose aspirin with reduced
risk of bleeding. Few data are available on contemporary aspirin dosing patterns
after MI in the United States METHODS AND RESULTS: Aspirin dosing from 221 199
patients with MI (40.2% ST-segment-elevation MI) from 525 US hospitals enrolled
in the National Cardiovascular Data Registry's (NCDR's) Acute Coronary Treatment
and Intervention Outcomes Network Registry-Get with the Guidelines were
described, overall and in clinically relevant subgroups. High-dose aspirin was
defined as 325 mg and low dose as 81 mg. Between January 2007 and March 2011,
60.9% of patients with acute MI were discharged on high-dose aspirin, 35.6% on
low-dose aspirin, and 3.5% on other doses. High-dose aspirin was prescribed at
discharge to 73.0% of patients treated with percutaneous coronary intervention
and 44.6% of patients managed medically. Among 9075 patients discharged on
aspirin, thienopyridine, and warfarin, 44.0% were prescribed high-dose aspirin.
Patients with an in-hospital major bleeding event were also frequently discharged
on high-dose aspirin (56.7%). A 25-fold variation in the proportion prescribed
high-dose aspirin at discharge was observed across participating centers.
CONCLUSIONS: Most US patients with MI continue to be discharged on high-dose
aspirin. Although aspirin dosing after percutaneous coronary intervention largely
reflected prevailing guidelines before 2012, high-dose aspirin was prescribed
with similar frequency in medically managed patients and to those in categories
expected to be at high risk for bleeding. Wide variability in the proportional
use of high-dose aspirin across centers suggests significant influence from local
practice habits and uncertainty about appropriate aspirin dosing.
PMID- 25116898
TI - Examination of the treatment selection process in a multicenter observational
study.
AB - BACKGROUND: Many multicenter clinical trials use permuted-block randomization to
create balanced treatment allocations within clinical centers. Unlike randomized
trials, observational studies do not control treatment allocation, and
statistical models are used to adjust for measured confounders. For many
observational data analyses, the variability in the treatment selection process
within clinical centers is ignored. Furthermore, there is no consensus on the
best approach for dealing with variability in the treatment selection process
across clinical centers. METHODS AND RESULTS: Individuals aged >=65 years
receiving either drug-eluting stents or bare metal stents were included. A cohort
of 262 700 patients from 650 CathPCI Registry sites was followed up for a median
of 15 months. Propensity score models were estimated to describe the process used
to select drug-eluting stents across the study population. Substantial
variability in the use of drug-eluting stents at the clinical center level was
observed-even after accounting for differences in patient and clinical center
characteristics. By refitting and matching propensity scores within clinical
centers, a balanced cohort on treatment allocation and prognostic factors was
obtained. This approach generated an estimated hazard ratio that was
qualitatively similar to standard regression models and other propensity score
approaches. CONCLUSIONS: Substantial variability in treatment selection existed
between clinical centers. Matching recalibrated propensity scores within clinical
centers has the potential to reduce a source of bias in multicenter observational
studies. This methodology cannot eliminate all potential for biases; however, it
removes the potential bias from site-level factors.
PMID- 25116899
TI - Trapping atmospheric CO2 with gold.
AB - The ability of gold-hydroxides to fix CO2 is reported. [Au(IPr)(OH)] and
[{Au(IPr)}2(MU-OH)][BF4] react with atmospheric CO2 to form the trigold carbonate
complex [{Au(IPr)}3(MU(3)-CO3)][BF4]. Reactivity studies revealed that this
complex behaves as two basic and one cationic Au centres, and that it is
catalytically active. DFT calculations and kinetic experiments have been carried
out.
PMID- 25116894
TI - Three-dimensional in vitro tumor models for cancer research and drug evaluation.
AB - Cancer occurs when cells acquire genomic instability and inflammation, produce
abnormal levels of epigenetic factors/proteins and tumor suppressors, reprogram
the energy metabolism and evade immune destruction, leading to the disruption of
cell cycle/normal growth. An early event in carcinogenesis is loss of polarity
and detachment from the natural basement membrane, allowing cells to form
distinct three-dimensional (3D) structures that interact with each other and with
the surrounding microenvironment. Although valuable information has been
accumulated from traditional in vitro studies in which cells are grown on flat
and hard plastic surfaces (2D culture), this culture condition does not reflect
the essential features of tumor tissues. Further, fundamental understanding of
cancer metastasis cannot be obtained readily from 2D studies because they lack
the complex and dynamic cell-cell communications and cell-matrix interactions
that occur during cancer metastasis. These shortcomings, along with lack of
spatial depth and cell connectivity, limit the applicability of 2D cultures to
accurate testing of pharmacologically active compounds, free or sequestered in
nanoparticles. To recapitulate features of native tumor microenvironments,
various biomimetic 3D tumor models have been developed to incorporate cancer and
stromal cells, relevant matrix components, and biochemical and biophysical cues,
into one spatially and temporally integrated system. In this article, we review
recent advances in creating 3D tumor models employing tissue engineering
principles. We then evaluate the utilities of these novel models for the testing
of anticancer drugs and their delivery systems. We highlight the profound
differences in responses from 3D in vitro tumors and conventional monolayer
cultures. Overall, strategic integration of biological principles and engineering
approaches will both improve understanding of tumor progression and invasion and
support discovery of more personalized first line treatments for cancer patients.
PMID- 25116901
TI - An ionizing radiation sensor using a pre-programmed MAHAOS device.
AB - Metal-aluminum oxide-hafnium aluminum oxide-silicon oxide-silicon (hereafter
MAHAOS) devices can be candidates for ionizing radiation sensor applications. In
this work, MAHAOS devices (SONOS-like structures with high k stack gate
dielectric) were studied regarding the first known characterization of the
ionization radiation sensing response. The change of threshold voltage V(T) for a
MAHAOS device after gamma ray exposure had a strong correlation to the total
ionization dose (TID) of gamma radiation up to at least 5 Mrad TID. In this
paper, the gamma radiation response performances of the pre-programmed and virgin
(non-pre-programmed) MAHAOS devices are presented. The experimental data show
that the change of VT for the pre-programmed MAHAOS device with gamma irradiation
is very significant. The data of pre-programmed MAHAOS devices written by 5 Mrad
TID of gamma radiation was also stable for a long time with data storage. The
sensing of gamma radiation by pre-programmed MAHAOS devices with high k stack
gate dielectric reported in this study has demonstrated their potential
application for non-volatile ionizing radiation sensing technology in the future.
PMID- 25116900
TI - The benefit of specialized team approaches in patients with acute kidney injury
undergoing continuous renal replacement therapy: propensity score matched
analysis.
AB - INTRODUCTION: Continuous renal replacement therapy (CRRT) has been widely used in
critically ill acute kidney injury (AKI) patients. Moreover, some centers operate
a specialized CRRT team (SCT) composed of physicians and nurses, but few studies
have yet determined the superiority of SCT control. METHODS: A total of 334 among
534 patients in the original cohort, who started CRRT for severe AKI between
August 2007 and September 2009 in Yonsei University Health System and were
matched with a propensity score (PS), were divided into two groups based on SCT
application. Moreover, we compared CRRT-related outcomes including down-time per
day and lost time per filter-exchange between the two groups. The primary
outcomes were 28- and 90-day all-cause mortality, and the secondary outcomes were
the rates of renal function recovery at 28- and 90-day. RESULTS: The down-time
per day, lost time per filter-exchange, and red blood cell-transfused numbers
during CRRT treatment were significantly lower after SCT approach compared with
the group before SCT, while net ultrafiltration rate in the after SCT group was
significantly higher compared to the before SCT group. During the study period,
the 28- and 90-day all-cause mortality rates were significantly decreased after
SCT application. Cox regression analysis revealed that 28- and 90-day all-cause
mortality rates were significantly lower under SCT control, after adjusting for
primary diagnosis, emergent surgical cases, Charlson Comorbidity Index and
biochemical parameters. However, there were no significant differences in the
rate of renal function recovery before and after SCT approach in CRRT.
CONCLUSIONS: A well-organized CRRT team could be beneficial for clinical outcomes
through improving quality of care in AKI patients requiring CRRT treatment in the
ICU.
PMID- 25116902
TI - LiftingWiSe: a lifting-based efficient data processing technique in wireless
sensor networks.
AB - Monitoring thousands of objects which are deployed over large-hard-to-reach
areas, is an important application of the wireless sensor networks (WSNs). Such
an application requires disseminating a large amount of data within the WSN. This
data includes, but is not limited to, the object's location and the environment
conditions at that location. WSNs require efficient data processing and
dissemination processes due to the limited storage, processing power, and energy
available in the WSN nodes. The aim of this paper is to propose a data processing
technique that can work under constrained storage, processing, and energy
resource conditions. The proposed technique utilizes the lifting procedure in
processing the disseminated data. Lifting is usually used in discrete wavelet
transform (DWT) operations. The proposed technique is referred to as LiftingWiSe,
which stands for Lifting-based efficient data processing technique for Wireless
Sensor Networks. LiftingWiSe has been tested and compared to other relevant
techniques from the literature. The test has been conducted via a simulation of
the monitored field and the deployed wireless sensor network nodes. The
simulation results have been analyzed and discussed.
PMID- 25116903
TI - Enhanced ethanol gas sensing properties of SnO2-core/ZnO-shell nanostructures.
AB - An inexpensive single-step carbon-assisted thermal evaporation method for the
growth of SnO2-core/ZnO-shell nanostructures is described, and the ethanol
sensing properties are presented. The structure and phases of the grown
nanostructures are investigated by field-emission scanning electron microscopy
(FESEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD)
techniques. XRD analysis indicates that the core-shell nanostructures have good
crystallinity. At a lower growth duration of 15 min, only SnO2 nanowires with a
rectangular cross-section are observed, while the ZnO shell is observed when the
growth time is increased to 30 min. Core-shell hierarchical nanostructures are
present for a growth time exceeding 60 min. The growth mechanism for SnO2
core/ZnO-shell nanowires and hierarchical nanostructures are also discussed. The
sensitivity of the synthesized SnO2-core/ZnO-shell nanostructures towards ethanol
sensing is investigated. Results show that the SnO2-core/ZnO-shell nanostructures
deposited at 90 min exhibit enhanced sensitivity to ethanol. The sensitivity of
SnO2-core/ZnO-shell nanostructures towards 20 ppm ethanol gas at 400 degrees C
is about ~5-times that of SnO2 nanowires. This improvement in ethanol gas
response is attributed to high active sensing sites and the synergistic effect of
the encapsulation of SnO2 by ZnO nanostructures.
PMID- 25116905
TI - An energy-efficient and compact clustering scheme with temporary support nodes
for cognitive radio sensor networks.
AB - A cognitive radio sensor network (CRSN) is a wireless sensor network whose sensor
nodes are equipped with cognitive radio capability. Clustering is one of the most
challenging issues in CRSNs, as all sensor nodes, including the cluster head,
have to use the same frequency band in order to form a cluster. However, due to
the nature of heterogeneous channels in cognitive radio, it is difficult for
sensor nodes to find a cluster head. This paper proposes a novel energy-efficient
and compact clustering scheme named clustering with temporary support nodes
(CENTRE). CENTRE efficiently achieves a compact cluster formation by adopting two
phase cluster formation with fixed duration. By introducing a novel concept of
temporary support nodes to improve the cluster formation, the proposed scheme
enables sensor nodes in a network to find a cluster head efficiently. The
performance study shows that not only is the clustering process efficient and
compact but it also results in remarkable energy savings that prolong the overall
network lifetime. In addition, the proposed scheme decreases both the clustering
overhead and the average distance between cluster heads and their members.
PMID- 25116904
TI - A review of brain-computer interface games and an opinion survey from
researchers, developers and users.
AB - In recent years, research on Brain-Computer Interface (BCI) technology for
healthy users has attracted considerable interest, and BCI games are especially
popular. This study reviews the current status of, and describes future
directions, in the field of BCI games. To this end, we conducted a literature
search and found that BCI control paradigms using electroencephalographic signals
(motor imagery, P300, steady state visual evoked potential and passive approach
reading mental state) have been the primary focus of research. We also conducted
a survey of nearly three hundred participants that included researchers, game
developers and users around the world. From this survey, we found that all three
groups (researchers, developers and users) agreed on the significant influence
and applicability of BCI and BCI games, and they all selected prostheses,
rehabilitation and games as the most promising BCI applications. User and
developer groups tended to give low priority to passive BCI and the whole head
sensor array. Developers gave higher priorities to "the easiness of playing" and
the "development platform" as important elements for BCI games and the market.
Based on our assessment, we discuss the critical point at which BCI games will be
able to progress from their current stage to widespread marketing to consumers.
In conclusion, we propose three critical elements important for expansion of the
BCI game market: standards, gameplay and appropriate integration.
PMID- 25116906
TI - Warranty periods for normal myocardial perfusion stress SPECT.
AB - BACKGROUND: To assess different warranty periods following a normal myocardial
perfusion SPECT based on patients' clinical characteristics and the type of
stress performed. METHODS AND RESULTS: A study was done of 2,922 consecutive
patients (62.9 +/- 13 years; 53.4% women) with a normal stress-rest SPECT. The
warranty period was defined as the period during which patients remained at a low
risk (<1% events/year) of total mortality (TM), or hard events (HE) (cardiac
death or non-fatal myocardial infarction). Of these patients, 2,051 were given an
exercise myocardial perfusion imaging (Ex-MPI); 461 submaximal exercise plus
dipyridamole (Ex+Dipy-MPI); and 410 dipyridamole (Dipy-MPI). During a mean follow
up of 5 +/- 3.3 years, a significant reduction (P < .05) of the warranty period
for TM (13.5, 9.6 and 8 months) and HE (34.8, 20.5 and 8.2 months) was observed,
for Ex-MPI, Ex+Dipy-MPI and Dipy-MPI, respectively. Other warranty period
determinants were the clinical variables of age, sex, diabetes and known coronary
artery disease. An abnormal left ventricular ejection fraction on gated-SPECT
also significantly shortened the warranty period for HE in patients undergoing
Ex+Dipy-MPI (P = .001) or Dipy-MPI alone (P = .007). CONCLUSIONS: The warranty
period for a normal stress-rest SPECT is highly variable since it is primarily
determined by the type of stress, the patient's clinical characteristics and
LVEF.
PMID- 25116909
TI - Small molecules: from structural diversity to signalling and regulatory roles.
PMID- 25116908
TI - Tai chi meditation effects on nuclear factor-kappaB signaling in lonely older
adults: a randomized controlled trial.
PMID- 25116910
TI - Topical calcium carbonate soda crystals for refractory cancer-related lower limb
edema.
PMID- 25116911
TI - What is different about patients with hematologic malignancies? A retrospective
cohort study of cancer patients referred to a hospice research network.
AB - CONTEXT: Although much is known about solid tumor patients who use hospice, the
hematologic malignancies hospice population is inadequately described.
OBJECTIVES: To compare the characteristics and outcomes of hospice patients with
hematologic malignancies to those with solid tumors. METHODS: We extracted
electronic patient data (2008-2012) from a large hospice network (Coalition of
Hospices Organized to Investigate Comparative Effectiveness) and used bivariate
analyses to describe between-group differences. RESULTS: In total, 48,147
patients with cancer were admitted during the study period; 3518 (7.3%) had a
hematologic malignancy. These patients had significantly worse Palliative
Performance Scale scores (32% vs. 24% were below 40; P < 0.001) and shorter
lengths of stay (median 11 vs. 19 days; P < 0.001). They were more likely to die
within 24 hours of hospice enrollment (10.9% vs. 6.8%; odds ratio [OR] 1.66; 95%
CI 1.49, 1.86; P < 0.001) or within seven days (36% vs. 25.1%; OR 1.68; 95% CI
1.56, 1.81; P < 0.001) and were more likely to receive hospice services in an
inpatient or nursing home setting (OR 1.34; 95% CI 1.16, 1.56 and OR 1.54; 95% CI
1.39, 1.72; both P < 0.001). Among hematologic malignancy patients, those with
leukemia had the shortest survival (hazard ratio 1.23; 95% CI 1.13, 1.34; P <
0.001), and 40.3% used hospice for less than seven days (OR 1.31; 95% CI 1.11,
1.56; P = 0.002). CONCLUSION: Hospice patients with hematologic malignancies are
more seriously ill at the time of admission, with worse functional status and
shorter lengths of stay than other cancer patients. Differences in outcomes
suggest the need for targeted interventions to optimize hospice services for the
hematologic malignancies population, especially those with leukemia.
PMID- 25116913
TI - Predictors of pursuit of physician-assisted death.
AB - CONTEXT: Physician-assisted death (PAD) was legalized in 1997 by Oregon's Death
with Dignity Act. The States of Washington, Montana, Vermont, and New Mexico have
since provided legal sanction for PAD. Through 2013, 1173 Oregonians have
received a prescription under the Death with Dignity Act and 752 have died after
taking the prescribed medication in Oregon. OBJECTIVES: To determine the
predictive value of personal and interpersonal variables in the pursuit of PAD.
METHODS: Fifty-five Oregonians who either requested PAD or contacted a PAD
advocacy organization were compared with 39 individuals with advanced disease who
did not pursue PAD. We compared the two groups on responses to standardized
measures of depression, hopelessness, spirituality, social support, and pain. We
also compared the two groups on style of attachment to intimate others and
caregivers as understood through attachment theory. RESULTS: We found that PAD
requesters had higher levels of depression, hopelessness, and dismissive
attachment (attachment to others characterized by independence and self
reliance), and lower levels of spirituality. There were moderate correlations
among the variables of spirituality, hopelessness, depression, social support,
and dismissive attachment. There was a strong correlation between depression and
hopelessness. Low spirituality emerged as the strongest predictor of pursuit of
PAD in the regression analysis. CONCLUSION: Although some factors motivating
pursuit of PAD, such as depression, may be ameliorated by medical interventions,
other factors, such as style of attachment and sense of spirituality, are long
standing aspects of the individual that should be supported at the end of life.
Practitioners must develop respectful awareness and understanding of the
interpersonal and spiritual perspectives of their patients to provide such
support.
PMID- 25116912
TI - Organization of nursing and quality of care for veterans at the end of life.
AB - CONTEXT: The Veterans Health Administration (VA) has improved the quality of end
of-life (EOL) care over the past several years. Several structural and process
variables are associated with better outcomes. Little is known, however, about
the relationship between the organization of nursing care and EOL outcomes.
OBJECTIVES: To examine the association between the organization of nursing care,
including the nurse work environment and nurse staffing levels, and quality of
EOL care in VA acute care facilities. METHODS: Secondary analysis of linked data
from the Bereaved Family Survey (BFS), electronic medical record, administrative
data, and the VA Nursing Outcomes Database. The sample included 4908 veterans who
died in one of 116 VA acute care facilities nationally between October 2010 and
September 2011. Unadjusted and adjusted generalized estimating equations were
used to examine associations between nursing and BFS outcomes. RESULTS: BFS
respondents were 17% more likely to give an excellent overall rating of the
quality of EOL care received by the veteran in facilities with better nurse work
environments (P <= 0.05). The nurse work environment also was a significant
predictor of providers listening to concerns and providing desired treatments.
Nurse staffing was significantly associated with an excellent overall rating,
alerting of the family before death, attention to personal care needs, and the
provision of emotional support after the patient's death. CONCLUSION: Improvement
of the nurse work environment and nurse staffing in VA acute care facilities may
result in enhanced quality of care received by hospitalized veterans at the EOL.
PMID- 25116915
TI - Alnuheptanoid A: a new diarylheptanoid derivative from Alnus japonica.
AB - Extensive chromatographic investigation of the ethanolic extract of Alnus
japonica Steud stem bark led to the isolation of a new diarylheptanoid named
alnuheptanoid A [(5S)-7-(3,4-dihydroxyphenyl)-1-(4-hydroxyphenyl)-5-methoxyheptan
3-one] (8), together with seven known diarylheptanoid derivatives:
platyphyllenone (5), (5S)-1,7-bis(4-hydroxyphenyl)-5-methoxyheptan-3-one (6), 1
(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-4-hepten-3-one (7), hirsutenone (9),
(5R)-O-methylhirsutanonol (10), hirsutanonol (11) and oregonin (13), three
triterpenes: alpha-amyrin (1), betulinaldehyde (3) and betulinic acid (4), and
two sterols: beta-sitosterol (2) and daucosterol (12). Compound 6 was isolated
for the first time from natural source. The structures of the isolated compounds
were determined on the basis of spectroscopic measurements (UV, IR, HR-ESI-MS, 1D
and 2D NMR).
PMID- 25116914
TI - Predictors of thirst in intensive care unit patients.
AB - CONTEXT: Thirst is a pervasive, intense, and distressing symptom in intensive
care unit (ICU) patients. Although thirst may be avoided and/or treated, scant
data are available to help providers identify patients most in need. OBJECTIVES:
This study was designed to identify predictors of the presence, intensity, and
distress of thirst in ICU patients. METHODS: This descriptive cross-sectional
study enrolled 353 patients from three ICUs (medical-surgical, cardiac, and
neurological). To measure outcomes, patients were asked to report the presence of
thirst (yes/no) and, if present, to rate its intensity and distress on zero to 10
numeric rating scales (10=worst). Predictor variables were demographic (e.g.,
age), treatment-related (e.g., opioids), and biological (e.g., total body water).
Data were analyzed with logistic regression and truncated regression with alpha
preset at 0.05. RESULTS: Thirst presence was predicted by high opioid doses (>=
50 mg), high furosemide doses (>60 mg), selective serotonin reuptake inhibitors,
and low ionized calcium. Thirst intensity was predicted by patients not receiving
oral fluid and having a gastrointestinal (GI) diagnosis. Thirst distress was
predicted by mechanical ventilation, negative fluid balance, antihypertensive
medications, and a GI or "other" diagnosis. CONCLUSION: Thirst presence was
predicted by selected medications (e.g., opioids). Thirst intensity and/or thirst
distress were predicted by other treatments (e.g., mechanical ventilation) and
medical diagnoses (e.g., GI). This is one of the first studies describing
predictors of the multidimensional characteristics of thirst. Clinicians can use
these data to target ICU patients whose thirst might warrant treatment.
PMID- 25116917
TI - Known knowns, known unknowns, unknown unknowns and unknown knowns in DNA
barcoding: a comment on Dowton et al.
PMID- 25116919
TI - A leaky membrane and a sodium transporter at life's great divergence.
PMID- 25116916
TI - SILAC-based proteomic profiling of the human MDA-MB-231 metastatic breast cancer
cell line in response to the two antitumoral lactoferrin isoforms: the secreted
lactoferrin and the intracellular delta-lactoferrin.
AB - BACKGROUND: Lactoferrins exhibit antitumoral activities either as a secretory
lactoferrin or an intracellular delta-lactoferrin isoform. These activities
involve processes such as regulation of the cell cycle and apoptosis. While
lactoferrin has been shown to exert its function by activating different
transduction pathways, delta-lactoferrin has been proven to act as a
transcription factor. Like many tumor suppressors, these two proteins are under
expressed in several types of cancer, particularly in breast cancer.
METHODOLOGY/PRINCIPAL FINDINGS: In order to compare the differential effects of
the re-introduction of lactoferrin isoforms in breast cancer cells we chose the
cancerous mammary gland MDA-MB-231 cell line as a model. We produced a cell line
stably expressing delta-lactoferrin. We also treated these cells with fresh
purified human breast lactoferrin. We performed two quantitative proteomic
studies in parallel using SILAC coupled to mass spectrometry in order to compare
the effects of different doses of the two lactoferrin isoforms. The proteome of
untreated, delta-lactoferrin expressing and human lactoferrin treated MDA-MB-231
cells were compared. Overall, around 5300 proteins were identified and quantified
using the in-house developed MFPaQ software. Among these, expression was
increased by 1.5-fold or more for around 300 proteins in delta-lactoferrin
expressing cells and 190 proteins in lactoferrin treated cells. At the same time,
about 200 and 40 proteins were found to be downregulated (0-0.7-fold) in response
to delta-lactoferrin and lactoferrin, respectively. CONCLUSIONS/SIGNIFICANCE: Re
introduction of delta-lactoferrin and lactoferrin expression in MDA-MB-231 mainly
leads to modifications of protein profiles involved in processes such as
proliferation, apoptosis, oxidative stress, the ubiquitin pathway, translation
and mRNA quality control. Moreover, this study identified new target genes of
delta-lactoferrin transcriptional activity such as SelH, GTF2F2 and UBE2E1.
PMID- 25116920
TI - Otoacoustic emissions before and after listening to music on a personal player.
AB - BACKGROUND: The problem of the potential impact of personal music players on the
auditory system remains an open question. The purpose of the present study was to
investigate, by means of otoacoustic emissions (OAEs), whether listening to music
on a personal player affected auditory function. MATERIAL/METHODS: A group of 20
normally hearing adults was exposed to music played on a personal player.
Transient evoked OAEs (TEOAEs) and distortion product OAEs (DPOAEs), as well as
pure tone audiometry (PTA) thresholds, were tested at 3 stages: before,
immediately after, and the next day following 30 min of exposure to music at 86.6
dBA. RESULTS: We found no statistically significant changes in OAE parameters or
PTA thresholds due to listening to the music. CONCLUSIONS: These results suggest
that exposure to music at levels similar to those used in our study does not
disturb cochlear function in a way that can be detected by means of PTA, TEOAE,
or DPOAE tests.
PMID- 25116921
TI - Modeling luminal breast cancer heterogeneity: combination therapy to suppress a
hormone receptor-negative, cytokeratin 5-positive subpopulation in luminal
disease.
AB - INTRODUCTION: Many Luminal breast cancers are heterogeneous, containing
substantial numbers of estrogen (ER) and progesterone (PR) receptor-negative
cells among the ER+ PR+ ones. One such subpopulation we call "Luminobasal" is ER
, PR- and cytokeratin 5 (CK5)-positive. It is not targeted for treatment.
METHODS: To address the relationships between ER+PR+CK5- and ER-PR-CK5+ cells in
Luminal cancers and tightly control their ratios we generated isogenic pure
Luminal (pLUM) and pure Luminobasal (pLB) cells from the same parental Luminal
human breast cancer cell line. We used high-throughput screening to identify pLB
specific drugs and examined their efficacy alone and in combination with hormone
therapy in mixed-cell tumor models. RESULTS: We show that pLUM and MCF7 cells
suppress proliferation of pLB cells in mixed-cell 3D colonies in vitro and that
pLUM cells suppress growth of pLB cells in mixed-cell xenografts in vivo. High
throughput screening of 89 FDA-approved oncology drugs shows that pLB cells are
sensitive to monotherapy with the epidermal growth factor receptor (EGFR)
inhibitors gefitinib and erlotinib. By exploiting mixed-cell 3D colonies and
mixed-cell solid mouse tumors models we demonstrate that combination therapy with
gefitinib plus the anti-estrogen fulvestrant constitutes a robust treatment
strategy. CONCLUSIONS: We propose that response to combination endocrine/EGFR
inhibitor therapies in heterogeneous Luminal cancers may improve long-term
survival in patients whose primary tumors have been preselected for appropriate
biomarkers, including ER, PR, CK5 and EGFR.
PMID- 25116930
TI - Characteristics of the orthostatic cardiovascular response in adolescent patients
with psychogenic fever.
PMID- 25116923
TI - English Longitudinal Study of Aging: can Internet/E-mail use reduce cognitive
decline?
AB - BACKGROUND: Cognitive decline is a major risk factor for disability, dementia,
and death. The use of Internet/E-mail, also known as digital literacy, might
decrease dementia incidence among the older population. The aim was to
investigate whether digital literacy might be associated with decreased cognitive
decline in older adulthood. METHODS: Data from the English Longitudinal Study of
Aging cohort with 6,442 participants aged 50-89 years, followed for 8 years, with
baseline cognitive testing and four additional time points. The main outcome
variable was the relative percentage change in delayed recall from a 10-word-list
learning task across five separate measurement points. In addition to digital
literacy, socioeconomic variables, including wealth and education, comorbidities,
and baseline cognitive function were included in predictive models. The analysis
used Generalized Estimating Equations. RESULTS: Higher education, no functional
impairment, fewer depressive symptoms, no diabetes, and Internet/E-mail use
predicted better performance in delayed recall. CONCLUSIONS: Digital literacy may
help reduce cognitive decline among persons aged between 50 and 89 years.
PMID- 25116922
TI - New method for sperm evaluation by 3-dimensional laser scanning microscopy in
different laboratory animal species.
AB - Sperm analysis is one of the end points in reproductive toxicology studies.
Different methods for quantitative sperm analysis have been described. For
qualitative morphological sperm analysis, either such techniques or smears of
sperm and histological sperm staging are in use. Any of these methods provides
morphological results on a light microscopy level. Laser scanning microscopy is a
technique using a focused laser for scanning an object. The Olympus 3D Laser
Scanning Microscope LEXT OLS4000 with optional possibilities of differential
interference contrast provides a microscopic method for visualizing
microasperities, which are far beyond the resolving power of a typical light or
laser microscope. This technique was applied to sperm of mice, rats, rabbits, and
cynomolgus monkeys at magnifications up to *17 090. The obtained images are
comparable to those of a scanning electron microscope under relatively low-power
magnifications. Measurements on sperm parameters were taken by an integrated
image analysis software tool. Abnormalities were easily detectable.
PMID- 25116931
TI - Expression of vesicular glutamate transporter 3 mRNA in the brain and retina of
the pigeon.
AB - Vesicular glutamate transporters (vGluTs), which accumulate glutamate into
synaptic vesicles, are classified into three subtypes in mammalian brains:
vGluT1, vGluT2, and vGluT3. VGluT3 is localized in non-glutamatergic neurons of
the brain and retinal amacrine cells. In birds, the vGluT3 genome is found, but
its distribution in the brain or retina is unknown. The present study was
conducted to analyze vGluT3 cDNA sequence and elucidate its distribution in the
pigeon brain and retina. The vGluT3 cDNA comprises 1761bp and showed 95% and 88%
identity to the chicken and zebra finch vGluT3 cDNAs, respectively, and 74%
identity to human vGluT3 cDNA. In situ hybridization revealed that the vGluT3
mRNA was expressed in neurons of the caudal linear nucleus (LC) of the brain and
in amacrine cells of the inner nuclear layer of the retina. A combination of in
situ hybridization and serotonin immunohistochemistry revealed three types of
stained cells in LC and retina: vGluT3(+)/serotonin(+), vGluT3(+)/serotonin(-),
and vGluT3(-)/serotonin(+). The vGluT3(+)/serotonin(+) cells were approximately
22% in LC and 16% in the retina. The present results suggest that the pigeon
vGluT3 mRNA is comparable with the mammalian type.
PMID- 25116934
TI - Acute testicular fracture.
PMID- 25116935
TI - Different childhood adversities are associated with different symptom patterns in
adulthood.
PMID- 25116933
TI - Evaluation of functional genetic variants at 6q25.1 and risk of breast cancer in
a Chinese population.
AB - INTRODUCTION: Single-nucleotide polymorphisms (SNPs) at 6q25.1 that are
associated with breast cancer susceptibility have been identified in several
genome-wide association studies (GWASs). However, the exact causal variants in
this region have not been clarified. METHODS: In the present study, we genotyped
six potentially functional single-nucleotide polymorphisms (SNPs) within the
CCDC170 and ESR1 gene regions at 6q25.1 and accessed their associations with risk
of breast cancer in a study of 1,064 cases and 1,073 cancer-free controls in
Chinese women. The biological function of the risk variant was further evaluated
by performing laboratory experiments. RESULTS: Breast cancer risk was
significantly associated with three SNPs located at 6q25.1-rs9383935 in CCDC170
and rs2228480 and rs3798758 in ESR1-with variant allele attributed odds ratios
(ORs) of 1.38 (95% confidence interval (CI): 1.20 to 1.57, P=2.21*10(-6)), 0.84
(95% CI: 0.72 to 0.98, P=0.025) and 1.19 (95% CI: 1.04 to 1.37, P=0.013),
respectively. The functional variant rs9383935 is in high linkage disequilibrium
(LD) with GWAS-reported top-hit SNP (rs2046210), but only rs9383935 showed a
strong independent effect in conditional regression analysis. The rs9383935 risk
allele A showed decreased activity of reporter gene in both the MCF-7 and BT-474
breast cancer cell lines, which might be due to an altered binding capacity of
miR-27a to the 3' untranslated region (3' UTR) sequence of CCDC170. Real-time
quantitative reverse transcription PCR confirmed the correlation between
rs9383935 genotypes and CCDC170 expression levels. CONCLUSIONS: The results of
this study suggest that the functional variant rs9383935, located at the 3' UTR
of CCDC170, may be one candidate of the causal variants at 6q25.1 that modulate
the risk of breast cancer.
PMID- 25116936
TI - Does the majority always know best? Young children's flexible trust in majority
opinion.
AB - Copying the majority is generally an adaptive social learning strategy but the
majority does not always know best. Previous work has demonstrated young
children's selective uptake of information from a consensus over a lone
dissenter. The current study examined children's flexibility in following the
majority: do they overextend their reliance on this heuristic to situations where
the dissenting individual has privileged knowledge and should be trusted instead?
Four- to six- year-olds (N = 103) heard conflicting claims about the identity of
hidden drawings from a majority and a dissenter in two between-subject
conditions: in one, the dissenter had privileged knowledge over the majority (he
drew the pictures); in the other he did not (they were drawn by an absent third
party). Overall, children were less likely to trust the majority in the
Privileged Dissenter condition. Moreover, 5- and 6- year-olds made majority-based
inferences when the dissenter had no privileged knowledge but systematically
endorsed the dissenter when he drew the pictures. The current findings suggest
that by 5 years, children are able to make an epistemic-based judgment to decide
whether or not to follow the majority rather than automatically following the
most common view.
PMID- 25116937
TI - Value of water mazes for assessing spatial and egocentric learning and memory in
rodent basic research and regulatory studies.
AB - Maneuvering safely through the environment is central to survival of all animals.
The ability to do this depends on learning and remembering locations. This
capacity is encoded in the brain by two systems: one using cues outside the
organism (distal cues), allocentric navigation, and one using self-movement,
internal cues and sometimes proximal cues, egocentric navigation. Allocentric
navigation involves the hippocampus, entorhinal cortex, and surrounding
structures (e.g., subiculum); in humans this system encodes declarative memory
(allocentric, semantic, and episodic, i.e., memory for people, places, things,
and events). This form of memory is assessed in laboratory animals by many
methods, but predominantly the Morris water maze (MWM). Egocentric navigation
involves the dorsal striatum and connected structures; in humans this system
encodes routes and integrated paths and when over-learned becomes implicit or
procedural memory. Several allocentric methods for rodents are reviewed and
compared with the MWM with particular focus on the Cincinnati water maze (CWM).
MWM advantages include minimal training, no food deprivation, ease of testing,
reliable learning, insensitivity to differences in body weight and appetite,
absence of non-performers, control methods for performance effects, repeated
testing capability and other factors that make this test well-suited for
regulatory studies. MWM limitations are also reviewed. Evidence-based MWM design
and testing methods are presented. On balance, the MWM is arguably the preferred
test for assessing learning and memory in basic research and regulatory studies
and the CWM is recommended if two tests can be accommodated so that both
allocentric (MWM) and egocentric (CWM) learning and memory can be effectively and
efficiently assessed.
PMID- 25116938
TI - Preferences for the delivery of community pharmacy services to help manage
chronic conditions.
AB - BACKGROUND: To optimize positive outcomes, the design of new pharmacy services
should consider the preferences of consumers with chronic condition(s) and their
carers. OBJECTIVES: (i) To evaluate the relative importance of community pharmacy
service characteristics, from the perspective of consumers with chronic
condition(s) and carers; (ii) To compare consumer and carer preferences to health
professional beliefs about ideal service characteristics for consumers. METHOD: A
discrete choice experiment was completed by consumers with chronic condition(s)
and/or carers (n = 602) and health professionals (n = 297), recruited from four
regions in Australia. Participants were each randomized to one survey version
containing four (from a total 72) different choices between two new pharmacy
services. Consumer and carer participants were also given an 'opt out'
alternative of current service. Each service was described using six attributes
related to pharmacy service characteristics: continued medicines supply,
continuity and coordinated care, location, medication management, education and
information, and cost. RESULTS: Consumers and carers placed highest priority on
continued medicines supply by a pharmacist for regular and symptom flare up
medicines (100 priority points), a pharmacy located within a 'one-stop' health
center (61 points) and home delivery of medicines (52 points). Although continued
medicines supply was most important for consumers and carers, pharmacy location
was perceived by health professionals to be the most important characteristic for
consumers. Participants were less inclined to choose new services if their
current pharmacy offered high quality services that were person-centered, easy to
access and responsive to their needs. Younger, more highly educated and employed
participants, and those with established condition(s) were more likely to choose
new services. CONCLUSIONS: Person-centered care is a fundamental tenet for
pharmacy services. The provision of continued medicines supply (e.g. through
pharmacist prescribing), convenient and coordinated care delivered through a one
stop health centre, and home delivery of medicines, should be prioritized when
planning pharmacy services to best assist consumers to manage chronic conditions.
PMID- 25116940
TI - The effects of alloying and segregation for the reactivity and diffusion of
oxygen on Cu3Au(111).
AB - We report results of the segregation induced by the adsorption of O2 and the
barrier of the formation of Cu2O in Cu3Au(111) with an experimental and
theoretical approach. Oxidation by a hyperthermal O2 molecular beam (HOMB) was
investigated by X-ray photoemission spectroscopy in conjunction with a
synchrotron light source. From the incident-energy dependence of the measured O
uptake curve, dissociative adsorption of O2 is less effective on Cu3Au(111) than
on Cu(111). The dissociative adsorption is accompanied by the Cu segregation on
Cu3Au(111) as well as on Cu3Au(100) and Cu3Au(110). The obvious growth of Cu2O
for a 2.3 eV HOMB cannot be observed and it suggests that the Au-rich protective
layers prevent the diffusion of O atoms into the bulk. The theoretical approach
based on density functional theory indicates that O adsorption shows the same
behavior on Cu3Au(111) and on Cu(111). For the diffusion case, the barrier to
diffuse into the subsurface in segregated Cu3Au(111) is higher than in Cu(111).
This indicates that the segregated Au-rich layer in Cu3Au(111) works as a
protective layer.
PMID- 25116941
TI - Physical therapy in multiple sclerosis differs across Europe: information
regarding an ongoing study.
PMID- 25116939
TI - Crossover localisation is regulated by the neddylation posttranslational
regulatory pathway.
AB - Crossovers (COs) are at the origin of genetic variability, occurring across
successive generations, and they are also essential for the correct segregation
of chromosomes during meiosis. Their number and position are precisely
controlled, however the mechanisms underlying these controls are poorly
understood. Neddylation/rubylation is a regulatory pathway of posttranslational
protein modification that is required for numerous cellular processes in
eukaryotes, but has not yet been linked to homologous recombination. In a screen
for meiotic recombination-defective mutants, we identified several axr1 alleles,
disrupting the gene encoding the E1 enzyme of the neddylation complex in
Arabidopsis. Using genetic and cytological approaches we found that axr1 mutants
are characterised by a shortage in bivalent formation correlated with strong
synapsis defects. We determined that the bivalent shortage in axr1 is not due to
a general decrease in CO formation but rather due to a mislocalisation of class I
COs. In axr1, as in wild type, COs are still under the control of the ZMM group
of proteins. However, in contrast to wild type, they tend to cluster together and
no longer follow the obligatory CO rule. Lastly, we showed that this deregulation
of CO localisation is likely to be mediated by the activity of a cullin 4 RING
ligase, known to be involved in DNA damage sensing during somatic DNA repair and
mouse spermatogenesis. In conclusion, we provide evidence that the
neddylation/rubylation pathway of protein modification is a key regulator of
meiotic recombination. We propose that rather than regulating the number of
recombination events, this pathway regulates their localisation, through the
activation of cullin 4 RING ligase complexes. Possible targets for these ligases
are discussed.
PMID- 25116944
TI - Simultaneous imaging of both product ions: exploring gateway states for HCl as a
benchmark molecule.
AB - Simultaneous imaging of both positive and negative product ions is used to
exclusively study photoion pair formation free from interference of competing
fragmentation channels. Resonance enhanced multi-photon excitation allows us to
interrogate potential energy surfaces for vastly differing molecular geometries.
3D imaging provides complete fragment information. We applied the technique to
HCl as a benchmark and identified the gateway state leading to photoion pairs.
The approach can easily be applied to any molecule exhibiting a potential with an
attractive part at large internuclear distances.
PMID- 25116945
TI - Childhood maltreatment and somatic complaints among adult psychiatric
outpatients: exploring the mediating role of alexithymia.
PMID- 25116943
TI - Transcriptome sequencing reveals altered long intergenic non-coding RNAs in lung
cancer.
AB - BACKGROUND: Long intergenic non-coding RNAs (lncRNAs) represent an emerging and
under-studied class of transcripts that play a significant role in human cancers.
Due to the tissue- and cancer-specific expression patterns observed for many
lncRNAs it is believed that they could serve as ideal diagnostic biomarkers.
However, until each tumor type is examined more closely, many of these lncRNAs
will remain elusive. RESULTS: Here we characterize the lncRNA landscape in lung
cancer using publicly available transcriptome sequencing data from a cohort of
567 adenocarcinoma and squamous cell carcinoma tumors. Through this compendium we
identify over 3,000 unannotated intergenic transcripts representing novel
lncRNAs. Through comparison of both adenocarcinoma and squamous cell carcinomas
with matched controls we discover 111 differentially expressed lncRNAs, which we
term lung cancer-associated lncRNAs (LCALs). A pan-cancer analysis of 324
additional tumor and adjacent normal pairs enable us to identify a subset of
lncRNAs that display enriched expression specific to lung cancer as well as a
subset that appear to be broadly deregulated across human cancers. Integration of
exome sequencing data reveals that expression levels of many LCALs have
significant associations with the mutational status of key oncogenes in lung
cancer. Functional validation, using both knockdown and overexpression, shows
that the most differentially expressed lncRNA, LCAL1, plays a role in cellular
proliferation. CONCLUSIONS: Our systematic characterization of publicly available
transcriptome data provides the foundation for future efforts to understand the
role of LCALs, develop novel biomarkers, and improve knowledge of lung tumor
biology.
PMID- 25116946
TI - Perspectives of the antipsoriatic heliotherapy in Poland.
AB - Statistical analysis of the daily course of exposures to TL-01 tube radiation for
93 psoriatic patients from the Medical University of Lodz during 20-day
phototherapy shows that the dose of 1 J/cm(2) represents a unit of single
exposure necessary for psoriasis healing. This value is converted to the
antipsoriatic effective dose of 317.9 J/m(2) using the TL-01 lamp irradiance
spectrum and the antipsoriatic action spectrum. It is proposed that the daily
exposure of 317.9 J/m(2) serves as the standard antipsoriatic dose (SAPD)
providing a link between the cabinet and the out-door exposures and it could be
used for planning heliotherapy in Poland. A model is proposed to calculate
ambient antipsoriatic doses for 3 h exposures around the local noon (9 am-12 am
GMT) based on satellite measurements of ozone and cloud characteristics. The
model constants are determined by a comparison with pertaining antipsoriatic
doses measured by the Brewer spectrophotometer in central Poland. It is found
that 3 h exposures to solar radiation in the period 15 May-15 September provides
the mean (2005-2013) doses in the range 2.7-3.1 SAPD over Poland. Thus,
heliotherapy could be treated as an alternative to the cabinet phototherapy for
almost 4 months. It seems that the most effective site for antipsoriatic
heliotherapy is the south/east part of Poland (the Bieszczady Mountains). The
heliotherapy could be carried out in existing national health centers equipped
with the standard easy-to-use biometers for on-line monitoring of UV level and
controlling duration of sunbathing to avoid erythema risks. It is even possible
to control the antipsoriatic heliotherapy by a patient himself, using low-cost
hand-held instruments measuring UV index.
PMID- 25116947
TI - Influence of external, intrinsic and individual behaviour variables on serum
25(OH)D in a German survey.
AB - The objective of the present study was to identify external, intrinsic or
behavioural factors that significantly influenced serum 25-hydroxyvitamin D
(25(OH)D) concentrations in a German survey. Data from 3061 participants in the
Cooperative Health Research in the Region of Augsburg, Germany (KORA) F4 survey
were used to relate potential determinants to measured mean serum 25(OH)D
concentrations using multivariable regression models. The factors significantly
associated with hypovitaminosis D (defined as 25(OH)D<25 nmolL(-1)) were season
(winter, spring and autumn), urban environment and high body mass index. In
contrast, times spent in sunny regions, hours per day spent outdoors in the
summer as well as additional oral intake were associated with higher 25(OH)D
concentrations. These results suggest that mainly ambient UV exposure but also
individual behaviour are the most important determinants for personal 25(OH)D
concentrations. The analyses further showed that in winter 43% of subjects were
vitamin D deficient and 42% insufficient. Even in summer over half the population
has insufficient vitamin D status with 8% deficient and 47% insufficient.
Therefore measures to mitigate widespread vitamin D insufficiency such as regular
short-term sun exposure and/or improved dietary intake/supplementation
recommendations by public health bodies need to be considered.
PMID- 25116948
TI - Green synthesis of gold nanoparticles for staining human cervical cancer cells
and DNA binding assay.
AB - Gold nanoparticles have been functionalized by non-ionic surfactants
(polysorbates) used in pharmaceutical formulations. This results in the formation
of more well-dispersed gold nanoparticles (GNPs) than the GNPs formed in neat
water. The synthesized GNPs show good temporal stability. The synthesis
conditions are mild and environmentally benign. The GNPs can bind to ct-DNA and
displace bound dye molecules. The DNA-binding assay is significant as it
preliminarily indicated that DNA-GNP conjugates can be formed. Such conjugates
are extremely promising for applications in nanobiotechnology. The GNPs can also
stain the human cervical cancer (HeLa) cells over a wide concentration range
while remaining non-cytotoxic, thus providing a non invasive cell staining
method. This result is very promising as we observe staining of HeLa cells at
very low GNP concentrations (1 MUM) while the cell viability is retained even at
10-fold higher GNP concentrations.
PMID- 25116949
TI - GFS9/TT9 contributes to intracellular membrane trafficking and flavonoid
accumulation in Arabidopsis thaliana.
AB - Flavonoids are the most important pigments for the coloration of flowers and
seeds. In plant cells, flavonoids are synthesized by a multi-enzyme complex
located on the cytosolic surface of the endoplasmic reticulum, and they
accumulate in vacuoles. Two non-exclusive pathways have been proposed to mediate
flavonoid transport to vacuoles: the membrane transporter-mediated pathway and
the vesicle trafficking-mediated pathway. No molecules involved in the vesicle
trafficking-mediated pathway have been identified, however. Here, we show that a
membrane trafficking factor, GFS9, has a role in flavonoid accumulation in the
vacuole. We screened a library of Arabidopsis thaliana mutants with defects in
vesicle trafficking, and isolated the gfs9 mutant with abnormal pale tan-colored
seeds caused by low flavonoid accumulation levels. gfs9 is allelic to the
unidentified transparent testa mutant tt9. The responsible gene for these
phenotypes encodes a previously uncharacterized protein containing a region that
is conserved among eukaryotes. GFS9 is a peripheral membrane protein localized at
the Golgi apparatus. GFS9 deficiency causes several membrane trafficking defects,
including the mis-sorting of vacuolar proteins, vacuole fragmentation, the
aggregation of enlarged vesicles, and the proliferation of autophagosome-like
structures. These results suggest that GFS9 is required for vacuolar development
through membrane fusion at vacuoles. Our findings introduce a concept that plants
use GFS9-mediated membrane trafficking machinery for delivery of not only
proteins but also phytochemicals, such as flavonoids, to vacuoles.
PMID- 25116951
TI - Post-translational modifications of integrin ligands as pathogenic mechanisms in
disease.
AB - Protein post-translational modifications like glycation, carbamylation and
citrullination increase the functional diversity of the proteome but in disease
situations might do more harm than good. Post-translational modifications of ECM
proteins are thus appearing as mechanisms, which contribute to tissue dysfunction
in chronic kidney disease, in diabetes and in various inflammatory diseases. In
chronic renal failure, carbamylation could lead to kidney fibrosis. In diabetes,
high glucose levels lead to non-enzymatic glycation and cross-linking of
collagens, which contribute to tissue stiffening with consequences for
cardiovascular and renal functions. In inflammatory diseases, citrullination
deiminates arginine residues with possible consequences for integrin-mediated
cell adhesion to RGD- and GFOGER sequences in ECM proteins. Citrullination of
fibronectin was in one study suggested to affect cell adhesion by modifying the
heparin-binding site and not the RGD site. In a recent publication citrullination
of GFOGER sequences in collagen II was demonstrated to selectively affect
alpha10beta1 and alpha11beta1 integrin-mediated cell adhesion to collagen II,
with consequences for synovial fibroblast and stem cell adhesion and migration.
The implications of citrullination affecting integrin binding in disease open up
a new area of study and might have implications for the pathogenesis of
inflammatory diseases like rheumatoid arthritis and periodontitis.
PMID- 25116953
TI - TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role in monocyte
adhesion to vascular endothelium.
AB - Toll-like receptor 4 (TLR4) is known to mediate monocyte adhesion to endothelial
cells, however, its role on the expression of monocyte adhesion molecules is
unclear. In the present study, we investigated the role of TLR4 on the expression
of monocyte adhesion molecules, and determined the functional role of TLR4
induced adhesion molecules on monocyte adhesion to endothelial cells. When THP-1
monocytes were stimulated with Kdo2-Lipid A (KLA), a specific TLR4 agonist, Mac-1
expression was markedly increased in association with an increased adhesion of
monocytes to endothelial cells. These were attenuated by anti-Mac-1 antibody,
suggesting a functional role of TLR4-induced Mac-1 on monocyte adhesion to
endothelial cells. In monocytes treated with MK886, a 5-lipoxygenase (LO)
inhibitor, both Mac-1 expression and monocyte adhesion to endothelial cells
induced by KLA were markedly attenuated. Moreover, KLA increased the expression
of mRNA and protein of 5-LO, suggesting a pivotal role of 5-LO on these
processes. In in vivo studies, KLA increased monocyte adhesion to aortic
endothelium of wild-type (WT) mice, which was attenuated in WT mice treated with
anti-Mac-1 antibody as well as in TLR4-deficient mice. Taken together, TLR4
mediated expression of Mac-1 in monocytes plays a pivotal role on monocyte
adhesion to vascular endothelium, leading to increased foam cell formation in the
development of atherosclerosis.
PMID- 25116955
TI - Battle of the bulge: the yin and yang of vascular endothelial growth factor in
obesity.
PMID- 25116954
TI - Antiangiogenic actions of vascular endothelial growth factor-A165b, an inhibitory
isoform of vascular endothelial growth factor-A, in human obesity.
AB - BACKGROUND: Experimental studies suggest that visceral adiposity and adipose
tissue dysfunction play a central role in obesity-related cardiometabolic
complications. Impaired angiogenesis in fat has been implicated in the
development of adipose tissue hypoxia, capillary rarefaction, inflammation, and
metabolic dysregulation, but pathophysiological mechanisms remain unknown. In
this study, we examined the role of a novel antiangiogenic isoform of vascular
endothelial growth factor-A (VEGF-A), VEGF-A165b, in human obesity. METHODS AND
RESULTS: We biopsied paired subcutaneous and visceral adipose tissue in 40 obese
subjects (body mass index, 45+/-8 kg/m(2); age, 45+/-11 years) during bariatric
surgery and characterized depot-specific adipose tissue angiogenic capacity using
an established ex vivo assay. Visceral adipose tissue exhibited significantly
blunted angiogenic growth compared with subcutaneous fat (P<0.001) that was
associated with marked tissue upregulation of VEGF-A165b (P=0.004). The extent of
VEGF-A165b expression correlated negatively with angiogenic growth (r=-0.6,
P=0.006). Although recombinant VEGF-A165b significantly impaired angiogenesis,
targeted inhibition of VEGF-A165b with neutralizing antibody stimulated fat pad
neovascularization and restored VEGF receptor activation. Blood levels of VEGF
A165b were significantly higher in obese subjects compared with lean control
subjects (P=0.02), and surgical weight loss induced a marked decline in serumVEGF
A165b (P=0.003). CONCLUSIONS: We demonstrate that impaired adipose tissue
angiogenesis is associated with overexpression of a novel antiangiogenic factor,
VEGF-A165b, that may play a pathogenic role in human adiposopathy. Moreover,
systemic upregulation of VEGF-A165b in circulating blood may have wider-ranging
implications beyond the adipose milieu. VEGF-A165b may represent a novel area of
investigation to gain further understanding of mechanisms that modulate the
cardiometabolic consequences of obesity.
PMID- 25116958
TI - Analyte interactions with a new ditopic dansylamide-nitrobenzoxadiazole dyad: a
combined photophysical, NMR, and theoretical (DFT) study.
AB - We report herein the synthesis and photophysical studies on a new multicomponent
chemosensor dyad comprising two fluorescing units, dansylamide (DANS) and
nitrobenzoxadiazole (NBD). The system has been developed to investigate receptor
analyte binding interactions in the presence of both cations and anions in a
single molecular system. A dimethyl amino (in the DANS unit) group is used as a
receptor for cations, and acidic hydrogens of sulfonamide and the NBD group are
used as receptors for anions. The system is characterized by conventional
analytical techniques. The photophysical properties of this supramolecular system
in the absence and presence of various metal ions and nonmetal ions as additives
are investigated in an acetonitrile medium. Utility of this system in an aqueous
medium has also been demonstrated. The absorption and fluorescence spectrum of
the molecular system consists of a broad band typical of an intramolecular charge
transfer (ICT) transition. A low quantum yield and lifetime of the NBD moiety in
the present dyad indicates photoinduced electron transfer (PET) between DANS and
the NBD moiety. The fluorescence intensity of the system is found to decrease in
the presence of fluoride and acetate anions; however, the quenching is found to
be much higher for fluoride. This quenching behavior is attributed to the
enhanced PET from the anion receptor to the fluorophore moiety. The mechanistic
aspect of the fluoride ion signaling behavior has also been studied by infrared
(IR) and (1)H NMR experiments. The hydrogen bonding interaction between the
acidic NH protons of the DPN moiety and F(-) is found to be primarily responsible
for the fluoride selective signaling behavior. While investigating the cation
signaling behavior, contrary to anions, significant fluorescence enhancement has
been observed only in the presence of transition-metal ions. This behavior is
rationalized by considering the disruption of PET communication between DANS and
the NBD moiety due to transition-metal ion binding. Theoretical (density
functional theory) studies are also performed for the better understanding of the
receptor-analyte interaction. Interestingly, negative cooperativity in binding is
observed when the interaction of this system is studied in the presence of both
Zn(2+) and F(-). Fluorescence microscopy studies also revealed that the newly
developed fluorescent sensor system can be employed as an imaging probe in live
cells.
PMID- 25116959
TI - alpha-Glucosidase inhibitory activity of marine sponges collected in Mauritius
waters.
AB - This report describes the use of alpha-glucosidase to evaluate the anti-diabetic
potential of extracts from marine sponges collected in the Mauritius waters.
Initial screening at 1.0 mg/mL of 141 extracts obtained from 47 sponge species
revealed 10 extracts with inhibitory activity greater than 85%. Seven of the 10
extracts were further tested at 0.1 and 0.01 mg/mL and only the methanol extract
of two sponges namely Acanthostylotella sp. (ASSM) and Echinodictyum pykei (EPM)
showed inhibition activity greater than 60% at 0.1 mg/mL with an IC50 value of
0.16 +/- 0.02 and 0.04 +/- 0.01 mg/mL, respectively, while being inactive at 0.01
mg/mL.
PMID- 25116957
TI - Adaptive evolution and environmental durability jointly structure phylodynamic
patterns in avian influenza viruses.
AB - Avian influenza viruses (AIVs) have been pivotal to the origination of human
pandemic strains. Despite their scientific and public health significance,
however, there remains much to be understood about the ecology and evolution of
AIVs in wild birds, where major pools of genetic diversity are generated and
maintained. Here, we present comparative phylodynamic analyses of human and AIVs
in North America, demonstrating (i) significantly higher standing genetic
diversity and (ii) phylogenetic trees with a weaker signature of immune escape in
AIVs than in human viruses. To explain these differences, we performed
statistical analyses to quantify the relative contribution of several potential
explanations. We found that HA genetic diversity in avian viruses is determined
by a combination of factors, predominantly subtype-specific differences in host
immune selective pressure and the ecology of transmission (in particular, the
durability of subtypes in aquatic environments). Extending this analysis using a
computational model demonstrated that virus durability may lead to long-term,
indirect chains of transmission that, when coupled with a short host lifespan,
can generate and maintain the observed high levels of genetic diversity. Further
evidence in support of this novel finding was found by demonstrating an
association between subtype-specific environmental durability and predicted
phylogenetic signatures: genetic diversity, variation in phylogenetic tree branch
lengths, and tree height. The conclusion that environmental transmission plays an
important role in the evolutionary biology of avian influenza viruses-a
manifestation of the "storage effect"-highlights the potentially unpredictable
impact of wildlife reservoirs for future human pandemics and the need for
improved understanding of the natural ecology of these viruses.
PMID- 25116956
TI - Alternatively spliced tissue factor promotes plaque angiogenesis through the
activation of hypoxia-inducible factor-1alpha and vascular endothelial growth
factor signaling.
AB - BACKGROUND: Alternatively spliced tissue factor (asTF) is a novel isoform of full
length tissue factor, which exhibits angiogenic activity. Although asTF has been
detected in human plaques, it is unknown whether its expression in
atherosclerosis causes increased neovascularization and an advanced plaque
phenotype. METHODS AND RESULTS: Carotid (n=10) and coronary (n=8) specimens from
patients with stable or unstable angina were classified as complicated or
uncomplicated on the basis of plaque morphology. Analysis of asTF expression and
cell type-specific expression revealed a strong expression and colocalization of
asTF with macrophages and neovessels within complicated, but not uncomplicated,
human plaques. Our results showed that the angiogenic activity of asTF is
mediated via hypoxia-inducible factor-1alpha upregulation through integrins and
activation of phosphatidylinositol-3-kinase/Akt and mitogen-activated protein
kinase pathways. Hypoxia-inducible factor-1alpha upregulation by asTF also was
associated with increased vascular endothelial growth factor expression in
primary human endothelial cells, and vascular endothelial growth factor-Trap
significantly reduced the angiogenic effect of asTF in vivo. Furthermore, asTF
gene transfer significantly increased neointima formation and neovascularization
after carotid wire injury in ApoE(-/-) mice. CONCLUSIONS: The results of this
study provide strong evidence that asTF promotes neointima formation and
angiogenesis in an experimental model of accelerated atherosclerosis. Here, we
demonstrate that the angiogenic effect of asTF is mediated via the activation of
the hypoxia-inducible factor-1/vascular endothelial growth factor signaling. This
mechanism may be relevant to neovascularization and the progression and
associated complications of human atherosclerosis as suggested by the increased
expression of asTF in complicated versus uncomplicated human carotid and coronary
plaques.
PMID- 25116960
TI - Lack of depotentiation at basal ganglia output neurons in PD patients with
levodopa-induced dyskinesia.
AB - Parkinson's disease (PD), characterized by the loss of dopaminergic nigrostriatal
projections, is a debilitating neurodegenerative disease which produces
bradykinesia, rigidity, tremor and postural instability. The dopamine precursor
levodopa (L-Dopa) is the most effective treatment for the amelioration of PD
signs and symptoms, but long-term administration can lead to disabling motor
fluctuations and L-Dopa-induced dyskinesias. In animal models of PD, a form of
plasticity called depotentiation, or the reversal of previous potentiation, is
selectively lost after the development of dyskinetic movements following L-Dopa
treatment. We investigated whether low frequency stimulation (LFS) in the globus
pallidus internus (GPi) and substantia nigra pars reticulata (SNr) could induce
depotentiation at synapses that had already undergone high frequency stimulation
(HFS)-induced potentiation. To do so, we measured the field potentials (fEPs)
evoked by stimulation from a nearby microelectrode in 28 patients undergoing
implantation of deep brain stimulating (DBS) electrodes in the subthalamic
nucleus (STN) or GPi. We found that GPi and SNr synapses in patients with less
severe dyskinesia underwent greater depotentiation following LFS than in patients
with more severe dyskinesia. This demonstration of impaired depotentiation in
basal ganglia output nuclei in PD patients with dyskinesia is an important
validation of animal models of levodopa-induced dyskinesia. The ability of a
synapse to reverse previous potentiation may be crucial to the normal function of
the BG, perhaps by preventing saturation of the storage capacity required in
motor learning and optimal motor function. Loss of this ability at the output
nuclei may underlie, or contribute to the cellular basis of dyskinetic movements.
PMID- 25116962
TI - Psoriasis: the new and the old.
PMID- 25116961
TI - Expression patterns of sex-determination genes in single male and female embryos
of two Bactrocera fruit fly species during early development.
AB - In tephritids, the sex-determination pathway follows the sex-specific splicing of
transformer (tra) mRNA, and the cooperation of tra and transformer-2 (tra-2) to
effect the sex-specific splicing of doublesex (dsx), the genetic double-switch
responsible for male or female somatic development. The Dominant Male Determiner
(M) is the primary signal that controls this pathway. M, as yet uncharacterized,
is Y-chromosome linked, expressed in the zygote and directly or indirectly
diminishes active TRA protein in male embryos. Here we first demonstrated the
high conservation of tra, tra-2 and dsx in two Australian tephritids, Bactrocera
tryoni and Bactrocera jarvisi. We then used quantitative reverse transcription
PCR on single, sexed embryos to examine expression of the key sex-determination
genes during early embryogenesis. Individual embryos were sexed using molecular
markers located on the B. jarvisi Y-chromosome that was also introgressed into a
B. tryoni line. In B. jarvisi, sex-specific expression of tra transcripts
occurred between 3 to 6 h after egg laying, and the dsx isoform was established
by 7 h. These milestones were delayed in B. tryoni lines. The results provide a
time frame for transcriptomic analyses to identify M and its direct targets, plus
information on genes that may be targeted for the development of male-only lines
for pest management.
PMID- 25116963
TI - Therapeutic update on hyperhidrosis.
PMID- 25116964
TI - Sorafenib-associated psoriasiform eruption in a patient with hepatocellular
carcinoma.
PMID- 25116965
TI - Dramatic clearance of HIV-associated bowenoid papulosis using combined oral
acitretin and topical 5% imiquimod.
PMID- 25116966
TI - Ustekinumab treatment for psoriasis in 119 patients maintained on therapy for a
minimum of one year: a review.
AB - Ustekinumab is a human IgG1kappa monoclonal antibody that binds with high
affinity and specificity to the p40 protein subunit shared by both the
interleukin-12 and interleukin-23 cytokines. This study reviews clinical response
and adverse events in 119 psoriasis patients who have received ustekinumab for a
minimum of 1 year. The medical records of 119 psoriasis patients treated with
ustekinumab at our referral clinic in Dallas between 2009 and 2013 were reviewed
for response rates, side effects, and concomitant therapies. Of 119 patients, 117
(98%) had plaque type psoriasis, with 40 (34%) patients having psoriasis
affecting either their palms and/or soles. Forty-four (37%) patients had
psoriatic arthritis. The median follow-up period was 31 months. Fifty-six (47%)
of the 119 patients obtained near complete clearance (response of more than 90%
of initial body surface area involvement) upon the final follow-up visit or at
the time of ustekinumab treatment discontinuation. Concomitant systemic
treatments, primarily methotrexate, were given to 59 (50%) patients. Twenty-three
(19%) patients discontinued treatment, primarily for sub-optimal response or loss
of response. Fifty (42%) patients required either an increase in the dose of
ustekinumab to 90 mg and/or administration more frequently than every 12 weeks to
achieve and maintain psoriasis clearance.
PMID- 25116967
TI - A randomized, double-blinded trial evaluating the efficacy and tolerability of
vectical ointment (calcitriol 3 mcg/g ointment) when compared to betamethasone
diproprionate ointment (64 mg/g) in patients with nail psoriasis.
AB - OBJECTIVES: To demonstrate the efficacy and safety of calcitriol ointment (3
mcg/g) compared to betamethasone diproprionate ointment in the treatment of nail
psoriasis. DESIGN: Single-center, double-blind study. SETTING: One academic
center. PARTICIPANTS: 10 adult male and female subjects with psoriasis of the
fingernails and/or toenails. MEASUREMENTS: The primary efficacy evaluation was
the absolute reduction of nail thickness (mm) of the target nail. A secondary
endpoint was the improvement in the Physician Global Assessment score of disease
severity. RESULTS: Patients treated with either betamethasone diproprionate
ointment or calcitriol ointment demonstrated a similar reduction of nail
thickness of the selected target nail. The difference between the two groups was
not statistically significant (P=0.42). CONCLUSION: This small study illustrates
that calcitriol ointment may be as effective as betamethasone diproprionate in
the treatment of nail psoriasis, and its promise should be further investigated
in a subsequent larger trial.
PMID- 25116968
TI - Trends in systemic psoriasis treatment therapies from 1993 through 2010.
AB - BACKGROUND: Moderate-to-severe psoriasis generally requires systemic therapy, and
is often undertreated. OBJECTIVE: To determine and analyze what courses of
treatment and in what frequency are being utilized to combat psoriasis in the
United States. METHODS: Analysis of data from the National Ambulatory Medical
Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS)
of the National Center for Health Statistics. Data were analyzed to examine the
prevalence of different therapy techniques to combat psoriasis from 1993 through
2010. The trends for phototherapy, methotrexate (MTX), retinoids, cyclosporine A
(CSA), systemic steroids, and biologics were all analyzed over the entire 18-year
period and independently before and after the introduction of biologics in 2002.
RESULTS: From 1993 to 2010, the trend for total systemic treatments has not
significantly increased (P=0.5). Frequency of phototherapy treatments
significantly decreased from 1993 to 2010 (P<0.001). Since the introduction of
biologics in 2002, their frequency has significantly increased, becoming the most
frequently used treatment from 2008-2010 (P<0.0001). LIMITATIONS: Severity of
psoriasis was not recorded in the NAMCS and NHAMCS. CONCLUSIONS: The frequency of
systemic treatments to treat psoriasis has not significantly increased from 1993
to 2010. Despite the introduction of biologics, it appears that little progress
has been made in reducing under-treatment of moderate-to-severe psoriasis.
PMID- 25116969
TI - A randomized, prospective, sham-controlled study of localized narrow-band UVB
phototherapy in the treatment of plaque psoriasis.
AB - IMPORTANCE: UV phototherapy remains a useful and frequently employed treatment
for chronic plaque psoriasis. In those patients with plaque body surface area
less than 10%, targeted treatment is the safest and most effective modality.
OBJECTIVE: We aimed to evaluate the efficacy of the Levia(r) localized NB-UVB
phototherapy machine in the treatment of patients with symmetrical psoriatic
lesions. DESIGN: We performed a prospective, double-blinded, sham-treatment
controlled study of this device beginning March 2012 through April 2014. SETTING:
a comprehensive dermatology clinic in the northeastern United States.
PARTICIPANTS: 21 subjects with chronic plaque psoriasis. INTERVENTIONS: Each
patient had one lesion randomized to receive the Levia treatment and one lesion
(the control) treated with visible light. Treatment was administered three times
a week for twelve weeks. Target lesion score (TLS), a rating of 0-4 each of
erythema, scaling, and thickness, was measured biweekly by a blinded assessor,
and visual analogue scale of pruritus was recorded by subjects. MAIN OUTCOMES AND
MEASURES: The primary outcome, formulated prior to study initiation, was the
percentage of lesions achieving clear or almost clear TLS after 12 weeks of
treatment. Secondary endpoints included changes in target lesion pruritus VAS,
percentage improvement in TLS, and the percentage of subjects achieving 50%
improvement in TLS (TLS-50). RESULTS: The primary endpoint, TLS of three or less,
was not achieved (P=0.118), but the secondary endpoints of percentage improvement
in TLS (P=0.043) and TLS-50 (P=0.0195) were significantly superior in treated
compared to sham-treated lesions. Percentage improvement in pruritus VAS was not
significant (P=0.0565). CONCLUSIONS AND RELEVANCE: This device was found to be
efficacious, though not necessarily to the point of clearance, in the treatment
of psoriasis over a 12-week period. TRIAL REGISTRATION: www.clinicaltrials.gov,
identifier: NCT02107482, http://clinicaltrials.gov/show/NCT02107482
PMID- 25116970
TI - The use of self-administered subcutaneous methotrexate for the treatment of
psoriasis.
AB - For nearly 5 decades, methotrexate has been the backbone of moderate-to-severe
psoriasis treatment. The benefits of methotrexate therapy include reliable
efficacy, low cost, relative ease of administration, and its usefulness as part
of combination therapy regimens, making it a drug of choice for treating
psoriasis. While methotrexate can be administered orally, intravenously, or
intramuscularly, the self-administered subcutaneous use of the drug is the most
advantageous route. Subcutaneous methotrexate is associated with fewer adverse
events and higher absorption rates, accompanied by bioavailability that is both
linear and predictable throughout the range of possible doses. In addition, the
subcutaneous route, when compared with oral administration, facilitates improved
efficacy by promoting higher intracellular levels of long-chain methotrexate
polyglutamates. Taken together, these features allow patients the highest
probability of a successful therapeutic experience. Subcutaneous methotrexate
should be considered a viable option for the appropriate patient with moderate-to
severe psoriasis.
PMID- 25116971
TI - Tumor necrosis factor inhibitor therapy and myocardial infarction risk in
patients with psoriasis, psoriatic arthritis, or both.
AB - OBJECTIVES: To stratify MI risk reduction in those treated with a TNF inhibitor
for psoriasis only, psoriatic arthritis only, or both psoriasis and psoriatic
arthritis. DESIGN: Retrospective cohort study. SETTING: Between January 1, 2004
and November 30, 2010. PARTICIPANTS: At least 3 ICD9 codes for psoriasis (696.1)
or psoriatic arthritis (696.0) (without antecedent MI. INTERVENTION: None MAIN
OUTCOME MEASURE: Incident MI. RESULTS: When comparing to those not treated with
TNF inhibitors (reference group), of those treated with TNF inhibitors: those
with psoriasis only (N= 846) had a significant decrease in MI risk (hazard ratio
(HR), 0.26; 95% CI, 0.12-0.56); those with psoriatic arthritis only (N= 112) had
a non-significant decrease in MI risk (HR, 0.86; 95% CI, 0.28-2.70); those with
both psoriasis and psoriatic arthritis (N= 715) had a non-significant decrease in
MI risk (HR, 0.76; 95% CI, 0.47-1.24). CONCLUSIONS: In the TNF inhibitor cohort,
those with psoriasis only have the strongest association with MI risk reduction,
followed by those with psoriatic arthritis only, and then followed by those with
both psoriasis and psoriatic arthritis.
PMID- 25116972
TI - The basic science of natural ingredients.
AB - Herbal products have steadily gained popularity as alternatives to conventional,
synthetic medications and are sought after by patients for the treatment of
chronic dermatologic diseases and for cosmeceutical use. The production and
distribution of botanical extracts is largely unregulated and therefore extensive
research into their mechanism of action, safety, physiologic stability, and
optimal dosing has been overlooked. One of the major pathways through which
natural supplements, particularly polyphenols, act is via inhibition of oxidative
stress and its downstream mediators. Endogenous defense mechanisms are inadequate
to combat oxidative stress and therefore dietary and/or topical supplementation
with polyphenols are an important complementary preventative and therapeutic
strategy. This review focuses on the molecular targets of common polyphenols used
in topical preparations, particularly soy, green tea, oats, curcumin, and
silymarin. Continued research into bioavailability and function of these agents
will help translate their therapeutic potential to treat clinical disease.
PMID- 25116973
TI - Targeted therapy for cutaneous oncology: a review of novel treatment options for
non-melanoma skin cancer: part I.
AB - The field of cutaneous oncology is exploding with innovative treatment options,
specifically in the field of targeted therapy. These advances offer new hope to
select patients with high risk skin cancers. Here we provide a two part series
reviewing targeted therapy for non-melanoma skin cancer. We begin our discussion
with basal cell carcinoma, moving beyond the first-in-class hedgehog inhibitors
and highlighting promising clinical trials.
PMID- 25116974
TI - Targeted therapy for cutaneous oncology: a review of novel treatment options for
non-melanoma skin cancer: part II.
AB - The field of cutaneous oncology is exploding with innovative treatment options,
specifically in the field of targeted therapy. These advances offer new hope to
select patients with high risk skin cancers. In part two of our series on
targeted therapy for skin cancer, we focus our attention on squamous cell
carcinoma. We begin with the epidermal growth factor receptor inhibitors and
branch out into newer areas of active research.
PMID- 25116975
TI - The science behind common over-the-counter remedies used in dermatology.
AB - There are many over-the-counter products used to treat dermatological conditions.
Patients are inundated with information about these products. Dermatologists
often encounter questions about the usefulness of over-the-counter products as
anecdotal data about such products is often adapted as common practice in the
medical field. Modern dermatology training does not include pharmacological
education on many of the over-the-counter products commonly used by patients. In
this current age when patients have increasing interest in using "natural"
remedies, it is important that dermatologists can provide guidance to patients
regarding some of the most common products that they may encounter. This article
is designed to provide introductory information on the common uses for several
over-the-counter products as well as to display any evidence in support of these
products for dermatological diseases.
PMID- 25116976
TI - How suture technique affects the cosmetic outcome of cutaneous repairs.
AB - INTRODUCTION: Skin defects can be repaired via primary closure, secondary
intention healing, local and distant flaps, skin grafts or application of natural
and synthetic skin substitutes. When possible, primary linear repair is favored
due to simplicity, minimal morbidity and rapid healing. A number of suture
techniques are available to the surgeon for primary closure, the selection of
which depends on defect size, anatomic location, wound eversion, and tension.
OBJECTIVE: To review suture techniques and how they influence scar
cosmesis.
METHODS: PubMed was searched using the following key words:
cosme* in combination with cutaneous suture, simple interrupted,
simple running, running locked, vertical mattress, horizontal mattress, buried,
subcuticular, running vertical mattress, running horizontal mattress, buried
vertical mattress, butterfly suture, or pulley suture. Information
on study type, number of patients, age, gender, defect type, anatomic location,
suture technique, scar length, follow up, and outcomes measured were
tabulated.
RESULTS: Twenty-four articles - 17 prospective randomized
controlled trials including 1,473 subjects and 1,608 repairs and seven case
series including 465 subjects and repairs - were reviewed. Fifteen articles - 12
randomized controlled trials and three case series - demonstrated that aesthetic
outcome was influenced by suture technique, the majority of which showed
subcuticular closure to be superior to simple interrupted or simple running
sutures. No difference in aesthetic outcome was observed in nine studies, which
included 370 repairs.
DISCUSSION: Review of the literature supports the use
of subcuticular closure over simple interrupted or simple running sutures on the
trunk and extremities for improved aesthetic outcome.
PMID- 25116977
TI - Safety and effectiveness of ustekinumab for treatment of moderate to severe
psoriasis: a prospective study in a clinical setting.
AB - BACKGROUND: There are few studies analyzing the behavior of ustekinumab in the
complex management of psoriasis within diary clinical practice setting.
OBJECTIVE: To assess the utility of ustekinumab in a psoriasis unit. METHODS:
Analysis of the prospective data gathered during the follow-up of 30 consecutive
psoriasis patients treated with ustekinumab at a single referral centre. Three
effectiveness endpoints were defined 12 weeks, 28 and "long-term treatment". The
main outcome measure was improvement from baseline PASI at week 28 and at a point
of adjustment of prolonged treatment signed as "long-term treatment". RESULTS:
Overall 82.1% and 42.8% patients achieved respectively PASI75 and PASI90 response
rates at week 28. Long-term treatment maintained efficacy outcomes 81.5% and
40.7% PASI75 and PASI90, respectively were observed. At week 28, patients naive
to TNFalpha- blockers agents and patients with a baseline PASI >10 had better
PASI75 and PASI90 response rates than previously treated patients. CONCLUSIONS:
In clinical practice, the efficacy and patient adherence to ustekinumab are
excellent and even better to the data obtained in clinical trials. Clinical
indicators of psoriasis severity: previous treatments with tumor necrosis factor
alpha blockers agents and active treatment beside small increases in PASI
determine a delayed maximal response.
PMID- 25116978
TI - Disseminated botryomycosis: a rare presentation.
AB - Botryomycosis is a rare chronic bacterial infection of the skin or viscera that
resembles a deep fungal infection. Botryomycosis has two distinct patterns of
infection, visceral and cutaneous, the latter being the most common. Cutaneous
botryomycosis typically appears as a solitary plaque with superficial pustules.
Histologically, bacterial colonies are arranged in a distinctive "bunch of
grapes" pattern with surrounding eosinophilia, known as the Splendore-Hoeppli
phenomenon. Here we report a case of an 83-year-old female with disseminated
botryomycosis.
PMID- 25116979
TI - Flagellate erythema secondary to bleomycin: a new case report and review of the
literature.
AB - Bleomycin is an antibiotic with antineoplastic properties. It is used in the
treatment of different tumors in oncology. The mucocutaneous side effects of this
drug include ulcers, scaly erythematous and bullous lesions, sclerosis,
stomatitis, and pigmentary alterations. Flagellate erythema is a characteristic
hyperpigmentation of bleomycin. We report a case of flagellate erythema following
the administration of bleomycin in a 34-year-old woman with ovarian teratoma. She
developed linear lesions two weeks after the first injection of bleomycin.
Flagellate erythema is a specific reaction to bleomycin therapy, which occurs in
susceptible individuals independently of dose, route of administration, and type
of malignant disease treated.
PMID- 25116980
TI - Pseudoporphyria: discussion of etiologic agents.
AB - Pseudoporphyria describes a photodistributed bullous disorder with negative
urinary, fecal, and serum porphyrin studies. Although pseudoporphyria is thought
to be extremely rare (less than 100 reported cases4-5), we propose that this
entity is underreported. One author (KB) has seen four cases of pseudoporphyria
in the past four years. We describe a patient with nonpruritic, nonpainful bulla
on the dorsum of his hands. Biopsy revealed a split at the dermal-epidermal
junction; laboratory tests and urinary porphyrin evaluation were negative.
PMID- 25116981
TI - Why do we need another moisturizer for our acne patients?
PMID- 25116982
TI - The importance of photoprotection and moisturization in treating acne vulgaris.
AB - Skin care products are recognized by dermatologists as critical adjunctive
therapeutic modalities for patients suffering from acne vulgaris (AV).
Prescribing an acne medication without reviewing a patient's skin care regimen
can lead to poor compliance, intolerable side effects, and resulting patient and
physician frustration. Striking that delicate balance between maintaining the
skin barrier while controlling oil and shine has always been a challenge when
treating this chronic inflammatory condition, and it necessitates a unique set of
ingredients and formulation. Cetaphil(r) DermaControlTM Moisturizer SPF 30
(Galderma Laboratories, L.P., Fort Worth, Texas) is a new generation of skin care
specifically designed for acne-prone skin and acne-affected skin. Both
Cetaphil(r) DermaControlTM Foam Wash and Cetaphil DermaControl Moisturizer SPF 30
incorporate pharmacologically tested, state-of-the-art ingredients and
technologies that studies have shown impart substantial benefits to AV patients.
PMID- 25116985
TI - We the living.
PMID- 25116983
TI - Characteristics, treatment practices, and in-hospital outcomes of older adults
hospitalized with acute myocardial infarction.
AB - OBJECTIVES: To examine overall and decade-long trends (1999-2009),
characteristics, treatment practices, and hospital outcomes in individuals aged
65 and older hospitalized for acute myocardial infarction (AMI) and to describe
how these factors varied in the youngest, middle, and oldest-old individuals.
DESIGN: Retrospective cohort study. SETTING: Population-based Worcester Heart
Attack Study. MEASUREMENTS: Analyses were conducted to examine the
sociodemographic and clinical characteristics, cardiac treatments, and hospital
outcomes of older adults in three age strata (65-74, 75-84, >=85). PARTICIPANTS:
The study sample consisted of 3,851 individuals aged 65 and older hospitalized
with AMI every other year between 1999 and 2009; 32% were aged 65 to 74, 43% aged
75 to 84, and 25% aged 85 and older. RESULTS: Advancing age was inversely
associated with receipt of evidence-based cardiac therapies. After multivariable
adjustment, the odds of dying during hospitalization was 1.46 times as high in
participants aged 75 to 84 and 1.78 times as high in those aged 85 and older as
in those aged 65 to 74. The oldest-old participants had approximately 25% lower
odds of a prolonged hospital stay (>3 days) than those aged 65 to 74. Decade-long
trends in the principal study outcomes were also examined. Although the oldest
old participants hospitalized for AMI were at the greatest risk of dying,
persistent age-related differences were observed in hospital treatment practices.
Similar results were observed after excluding participants with a do-not
resuscitate order in their medical records. CONCLUSION: Although there are
persistent disparities in the care and outcomes of older adults hospitalized with
AMI, additional studies are needed to delineate the extent to which less
aggressive care reflects individual preferences and appropriate implementation of
palliative care approaches.
PMID- 25116986
TI - Movement velocity is a sensitive risk factor of falls in high-functioning older
adults.
PMID- 25116984
TI - Functional benefits of tai chi training in senior housing facilities.
AB - OBJECTIVES: To determine the effects of tai chi training on functional
performance and walking with and without the addition of the performance of a
cognitive task, in older adults living in supportive housing facilities. DESIGN:
Secondary data analysis comparing a single-blind, randomized controlled trial of
tai chi training with an attention-matched educational control intervention with
crossover to tai chi. SETTING: Two supportive housing facilities. PARTICIPANTS:
Sixty-six men and women living in supportive housing facilities entered the
study, and 57 aged 87+/-7 completed all study procedures. INTERVENTION:
Interventions consisted of two 1-hour-long instructor-led group sessions per week
for 12 weeks. Tai chi training consisted of movements based upon the Yang-style
short form. Educational sessions consisted of lectures and discussions of age
related health topics. MEASUREMENTS: Subjects were tested for physical function
(Short Physical Performance Battery, SPPB), balance (Berg Balance Scale, BBS),
mobility (timed up-and-go, TUG), and walking speed under normal and cognitive
dual-task conditions. RESULTS: The tai chi group exhibited greater improvement in
SPPB scores (baseline 8.1+/-2.9, follow-up 9.0+/-2.6) than controls (baseline
8.2+/-2.6, follow-up 8.2+/-2.6) (P=.005). Tai chi also increased normal and dual
task walking speed (P<.001) yet did not affect BBS (P=.02) or TUG (P=.02) after
accounting for multiple comparisons. The dual-task cost (percentage change) to
walking speed was unaffected. After the crossover tai chi intervention, the
control group improved performance in the SPPB, BBS, and TUG, and increased
walking speed under normal and dual-task conditions (P=.008). CONCLUSION: Tai chi
training may be a safe and effective therapy to help improve physical function
and dual-task walking in very old adults living in supportive housing facilities.
PMID- 25116987
TI - (Unsuccessful) binary modeling of successful aging in the oldest-old adults: a
call for continuum-based measures.
PMID- 25116989
TI - Hepatitis B and hepatitis C associated with risk of gallstone disease in elderly
adults.
PMID- 25116988
TI - Longitudinal neuropsychological performance of cognitive SuperAgers.
PMID- 25116990
TI - Falls prediction in acute care units: preliminary results from a prospective
cohort study.
PMID- 25116991
TI - Metabolic syndrome, executive dysfunction, and late-onset depression: just a
matter of white matter?
PMID- 25116992
TI - Rapidly progressive ataxia during rehabilitation and a difficult road to
diagnosis.
PMID- 25116993
TI - A rare entity with coffee-ground vomit in elderly adults: black esophagus.
PMID- 25116994
TI - Unexpected recovery of moderate cognitive impairment on treatment with oral
methylcobalamin.
PMID- 25116995
TI - When the inevitable question is asked.
PMID- 25116996
TI - Charlson comorbidity index in acutely hospitalized elderly adults.
PMID- 25116997
TI - Response letter to Martinez-Velilla and Zekry.
PMID- 25116999
TI - Response to David Nace and Paul Drinka.
PMID- 25116998
TI - Cranberry capsules reducing the incidence of what?
PMID- 25117000
TI - Reviewing the safety of loratadine for elderly adults: a potential shortcoming of
the 2012 Beers criteria.
PMID- 25117001
TI - Response to Marcio Galvao Oliveira et al.
PMID- 25117003
TI - Flavonoids with antimicrobial activity from the stem bark of Commiphora
pedunculata (Kotschy & Peyr.) Engl.
AB - The first reported investigation into the phytochemical constituents of
Commiphora pedunculata led to the isolation of two flavonoids: kaempferol and
dihydrokaempferol from the ethyl acetate-soluble fraction of the methanol extract
of the stem bark of the plant. The structures of these compounds were
characterised by comparing their spectral data including 1D and 2D NMR with those
reported in the literature. The two compounds were active against 6 out of 10
tested microorganisms including two resistant strains [methiciline-resistant
Staphylococcus aureus and vancomycin-resistant entrococci (VRE)], Candida
albicans and Escherichia coli. The zones of inhibition ranged between 24 and 30
mm for both compounds against the microorganisms. The MIC value was as low as
6.25 MUg/mL against VRE and Staphylococcus aureus. This is the first report of
the isolation of these compounds from the plant.
PMID- 25117002
TI - Probiotic properties of lactic acid bacteria isolated from water-buffalo
mozzarella cheese.
AB - This study evaluated the probiotic properties (stability at different pH values
and bile salt concentration, auto-aggregation and co-aggregation, survival in the
presence of antibiotics and commercial drugs, study of beta-galactosidase
production, evaluation of the presence of genes encoding MapA and Mub adhesion
proteins and EF-Tu elongation factor, and the presence of genes encoding
virulence factor) of four LAB strains (Lactobacillus casei SJRP35, Leuconostoc
citreum SJRP44, Lactobacillus delbrueckii subsp. bulgaricus SJRP57 and
Leuconostoc mesenteroides subsp. mesenteroides SJRP58) which produced
antimicrobial substances (antimicrobial peptides). The strains survived the
simulated GIT modeled in MRS broth, whole and skim milk. In addition, auto
aggregation and the cell surface hydrophobicity of all strains were high, and
various degrees of co-aggregation were observed with indicator strains. All
strains presented low resistance to several antibiotics and survived in the
presence of commercial drugs. Only the strain SJRP44 did not produce the beta
galactosidase enzyme. Moreover, the strain SJRP57 did not show the presence of
any genes encoding virulence factors; however, the strain SJRP35 presented
vancomycin resistance and adhesion of collagen genes, the strain SJRP44 harbored
the ornithine decarboxylase gene and the strain SJRP58 generated positive results
for aggregation substance and histidine decarboxylase genes. In conclusion, the
strain SJRP57 was considered the best candidate as probiotic cultures for further
in vivo studies and functional food products development.
PMID- 25117004
TI - The effects of sleep deprivation on emotional empathy.
AB - Previous studies have shown that sleep loss has a detrimental effect on the
ability of the individuals to process emotional information. In this study, we
tested the hypothesis that this negative effect extends to the ability of
experiencing emotions while observing other individuals, i.e. emotional empathy.
To test this hypothesis, we assessed emotional empathy in 37 healthy volunteers
who were assigned randomly to one of three experimental groups: one group was
tested before and after a night of total sleep deprivation (sleep deprivation
group), a second group was tested before and after a usual night of sleep spent
at home (sleep group) and the third group was tested twice during the same day
(day group). Emotional empathy was assessed by using two parallel versions of a
computerized test measuring direct (i.e. explicit evaluation of empathic concern)
and indirect (i.e. the observer's reported physiological arousal) emotional
empathy. The results revealed that the post measurements of both direct and
indirect emotional empathy of participants in the sleep deprivation group were
significantly lower than those of the sleep and day groups; post measurement
scores of participants in the day and sleep groups did not differ significantly
for either direct or indirect emotional empathy. These data are consistent with
previous studies showing the negative effect of sleep deprivation on the
processing of emotional information, and extend these effects to emotional
empathy. The findings reported in our study are relevant to healthy individuals
with poor sleep habits, as well as clinical populations suffering from sleep
disturbances.
PMID- 25117005
TI - Focal adhesion signaling and therapy resistance in cancer.
AB - Interlocking gene mutations, epigenetic alterations and microenvironmental
features perpetuate tumor development, growth, infiltration and spread.
Consequently, intrinsic and acquired therapy resistance arises and presents one
of the major goals to solve in oncologic research today. Among the myriad of
microenvironmental factors impacting on cancer cell resistance, cell adhesion to
the extracellular matrix (ECM) has recently been identified as key determinant.
Despite the differentiation between cell adhesion-mediated drug resistance
(CAMDR) and cell adhesion-mediated radioresistance (CAMRR), the underlying
mechanisms share great overlap in integrin and focal adhesion hub signaling and
differ further downstream in the complexity of signaling networks between tumor
entities. Intriguingly, cell adhesion to ECM is per se also essential for cancer
cells similar to their normal counterparts. However, based on the overexpression
of focal adhesion hub signaling receptors and proteins and a distinct addiction
to particular integrin receptors, targeting of focal adhesion proteins has been
shown to potently sensitize cancer cells to different treatment regimes including
radiotherapy, chemotherapy and novel molecular therapeutics. In this review, we
will give insight into the role of integrins in carcinogenesis, tumor progression
and metastasis. Additionally, literature and data about the function of focal
adhesion molecules including integrins, integrin-associated proteins and growth
factor receptors in tumor cell resistance to radio- and chemotherapy will be
elucidated and discussed.
PMID- 25117006
TI - Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: from
biology to clinical use.
AB - The tumor microenvironment includes a complicated network of physiological
gradients contributing to plasticity of tumor cells and heterogeneity of tumor
tissue. Hypoxia is a key component generating intratumoral oxygen gradients,
which affect the cellular expression program and lead to therapy resistance and
increased metastatic propensity of weakly oxygenated cell subpopulations. One of
the adaptive responses of tumor cells to hypoxia involves the increased
expression and functional activation of carbonic anhydrase IX (CA IX), a cancer
related cell surface enzyme catalyzing the reversible conversion of carbon
dioxide to bicarbonate ion and proton. Via its catalytic activity, CA IX
participates in regulation of intracellular and extracellular pH perturbations
that result from hypoxia-induced changes in cellular metabolism producing excess
of acid. Through the ability to regulate pH, CA IX also facilitates cell
migration and invasion. In addition, CA IX has non-catalytic function in cell
adhesion and spreading. Thus, CA IX endows tumor cells with survival advantages
in hypoxia/acidosis and confers an increased ability to migrate, invade and
metastasize. Accordingly, CA IX is expressed in a broad range of tumors, where it
is associated with prognosis and therapy outcome. Its expression pattern and
functional implications in tumor biology make CA IX a promising therapeutic
target, which can be hit either by immunotherapy with monoclonal antibodies or
with compounds inhibiting its enzyme activity. The first strategy has already
reached the clinical trials, whereas the second one is still in preclinical
testing. Both strategies indicate that CA IX can become a clinically useful
anticancer target, but urge further efforts toward better selection of patients
for immunotherapy and deeper understanding of tumor types, clinical situations
and synthetic lethality interactions with other treatment approaches.
PMID- 25117007
TI - Regulatory role of glycans in the control of hypoxia-driven angiogenesis and
sensitivity to anti-angiogenic treatment.
AB - Abnormal glycosylation is a typical hallmark of the transition from healthy to
neoplastic tissues. Although the importance of glycans and glycan-binding
proteins in cancer-related processes such as tumor cell adhesion, migration,
metastasis and immune escape has been largely appreciated, our awareness of the
impact of lectin-glycan recognition in tumor vascularization is relatively new.
Regulated glycosylation can influence vascular biology by controlling
trafficking, endocytosis and signaling of endothelial cell (EC) receptors
including vascular endothelial growth factor receptors, platelet EC adhesion
molecule, Notch and integrins. In addition, glycans may control angiogenesis by
regulating migration of endothelial tip cells and influencing EC survival and
vascular permeability. Recent evidence indicated that changes in the EC surface
glycome may also serve "on-and-off" switches that control galectin binding to
signaling receptors by displaying or masking-specific glycan epitopes. These
glycosylation-dependent lectin-receptor interactions can link tumor hypoxia to EC
signaling and control tumor sensitivity to anti-angiogenic treatment.
PMID- 25117008
TI - In vitro biological characterization of IFN-beta-1a major glycoforms.
AB - Recombinant human interferon beta-1a (IFN-beta-1a) is extensively used as the
first-line treatment of relapsing forms of multiple sclerosis. Its glycosylation
is recognized as having a complex impact on a wide range of molecule
characteristics and functions. The present study reports the enrichment of IFN
beta-1a glycoforms and their physicochemical and biological characterization by
means of electrospray ionization-mass spectrometry, sialic acid content, thermal
denaturation and various in vitro bioassays (antiproliferative, antiviral,
immunomodulatory and reporter gene assay). The glycoforms were fractionated by
means of cation-exchange chromatography using recombinant IFN-beta-1a derived
from Chinese Hamster Ovary cell culture as starting material. The obtained
fractions contained bi- and higher-antennarity glycans as described in the
European Pharmacopoeia monograph (Nr. 1639E, Interferon beta 1a concentrated
solution). The in vitro bioassay responses revealed a correlation mainly with the
glycan antennarity. It is therefore suggested that all glycoforms have biological
activity and play a role in modulating the overall IFN-beta biological activity
with higher-antennarity glycoforms being able to better sustain IFN-beta-1a
bioactivity over time. These data indicate the role of IFN-beta-1a glycosylation
in vivo and shed new light on the role of the glycosylation heterogeneity, in
particular with regard to antennarity, on biological properties of glycoproteins.
PMID- 25117009
TI - Assessment of cultivation factors that affect biomass and geraniol production in
transgenic tobacco cell suspension cultures.
AB - A large-scale statistical experimental design was used to determine essential
cultivation parameters that affect biomass accumulation and geraniol production
in transgenic tobacco (Nicotiana tabacum cv. Samsun NN) cell suspension cultures.
The carbohydrate source played a major role in determining the geraniol yield and
factors such as filling volume, inoculum size and light were less important.
Sucrose, filling volume and inoculum size had a positive effect on geraniol yield
by boosting growth of plant cell cultures whereas illumination of the cultures
stimulated the geraniol biosynthesis. We also found that the carbohydrates
sucrose and mannitol showed polarizing effects on biomass and geraniol
accumulation. Factors such as shaking frequency, the presence of conditioned
medium and solubilizers had minor influence on both plant cell growth and
geraniol content. When cells were cultivated under the screened conditions for
all the investigated factors, the cultures produced ~ 5.2 mg/l geraniol after 12
days of cultivation in shaking flasks which is comparable to the yield obtained
in microbial expression systems. Our data suggest that industrial experimental
designs based on orthogonal arrays are suitable for the selection of initial
cultivation parameters prior to the essential medium optimization steps. Such
designs are particularly beneficial in the early optimization steps when many
factors must be screened, increasing the statistical power of the experiments
without increasing the demand on time and resources.
PMID- 25117012
TI - Quality and safety in healthcare - a challenge accepted.
PMID- 25117010
TI - Hermansky-Pudlak syndrome. Overview of clinical and molecular features and case
report of a new HPS-1 variant.
AB - Hermansky-Pudlak syndrome (HPS) is a rare, autosomal recessive disorder affecting
lysosome-related organelles (LRO), including dense platelet granules. HPS causes
oculocutaneous hypopigmentation, bleeding diathesis and granulomatous colitis or
pulmonary fibrosis. To date, there is no curative treatment and the clinical
management depends on the severity of symptoms. A prompt diagnosis of HPS
patients could improve their quality of life and clinical management. However,
the absence of a specific platelet function test, the wide molecular
heterogeneity, and the lack of phenotype-genotype correlations hamper the rapid
diagnosis. Nine subtypes of HPS have been identified as a result of mutations in
nine genes that codify for proteins involved in formation and shuttle of the LRO.
The molecular characterization of patients and knowledge derived from animal
models of HPS contribute to the understanding of biogenesis and function of the
LRO. This paper describes a patient with a novel homozygous nonsense mutation
causing HPS and provides a review of the literature focusing on recent advances
in the molecular characterization and physiopathology of HPS.
PMID- 25117013
TI - Retrospective studies provide valuable information.
PMID- 25117014
TI - 'In somno securitas - semper vigilans'?
PMID- 25117015
TI - Continuous posterior TAP analgesia after laparoscopic colorectal surgery.
PMID- 25117016
TI - TAP block terminology.
PMID- 25117017
TI - Subcostal TAP block and postoperative respiratory function after abdominal
surgery.
PMID- 25117018
TI - Anaesthesia-related outcome after hip fracture.
PMID- 25117019
TI - A reply.
PMID- 25117020
TI - Cognitive aid for malignant hyperpyrexia.
PMID- 25117021
TI - SonixGPS - the role of operator experience.
PMID- 25117022
TI - A reply.
PMID- 25117023
TI - Driving advice after isoflurane anaesthesia.
PMID- 25117024
TI - The effect of general anaesthesia on memory in children.
PMID- 25117025
TI - Problem with Portex 'loss of resistance' syringes.
PMID- 25117026
TI - Main trunk crossover stenting in a patient with left internal thoracic artery-
protected single coronary artery.
AB - A 74-year-old man with single coronary artery and history of previous coronary
artery bypass graft (CABG) was admitted to our hospital with worsening angina.
Because of high risk of redo-CABG, we performed transradial percutaneous coronary
intervention against the just proximal left anterior descending coronary artery
(LAD) stenosis coexisting with short main trunk, anomalous right coronary artery
deriving from the mid LAD and patent left internal thoracic artery-distal LAD
graft. Under the guidance of IVUS, we successfully implanted an everolimus
eluting stent from the main trunk ostium to the proximal LAD without
complications.
PMID- 25117027
TI - Toxicity of naturally occurring Bio-fly and chitosan compounds to control the
Mediterranean fruit fly Ceratitis capitata (Wiedemann).
AB - The efficacy of five compounds of a biopolymer chitosan and Bio-fly (Beauveria
bassiana fungus) as biopesticide was evaluated on Ceratitis capitata under
laboratory conditions. The inhibitory effects on acetylcholinesterase (AChE) and
adenosinetriphosphatase (ATPase) as biochemical indicators were also determined
in vivo. The results indicated that B. bassiana based Bio-fly exhibited
significant toxicity against C. capitata (LC50 = 3008 and 3126 mg/L after 48 h in
females and males, respectively) followed by the derivatives of chitosan, N-(4
propylbenzyl)chitosan and N-(2-nitrobenzyl)chitosan. Bio-fly displayed remarkable
inhibition of AChE activity (IC50 = 2220 mg/L) while N-(2-chloro,6
flourobenzyl)chitosan, N-(4-propylbenzyl)chitosan and N-(3,4
methylenedioxybenzyl) chitosan had no significant difference in inhibitory
action. In adult males, N-(2-nitrobenzyl)chitosan exhibited the highest
inhibitory action (IC50 = 6569 mg/L). In addition, the toxic effects of the
tested compounds on the activity of ATPase indicated that highly significant
inhibition was found with N-(4-propylbenzyl)chitosan with an IC50 of 8194 and
8035 mg/L, in females and males, respectively.
PMID- 25117028
TI - The complex, non-monotonic thermal response of the volumetric space of simple
liquids.
AB - In this paper, an intricate effect of the isothermal compression of simple
liquids on their volumetric response is reported for alpha,omega-halogenoalkanes
as examples. We apply an accurate experimental technique, scanning
transitiometry, to directly measure isobaric thermal volume expansivities alphap
of the liquids in a wide density range. To thoroughly analyze the observed
intersection of the experimental isothermal pressure dependences of alphap, we
develop a class of equations of state derived in the density scaling regime for
molecular dynamics, finding successful temperature parameterizations of an
isothermal equation of state (EOS) intrinsically adapted to describe volumetric
data in an extremely wide density range. The EOS based analyses of the scanning
transitiometry data as a function of temperature T and pressure p undoubtedly
show that the previously considered crossing point of the isothermal dependences
alphap(p) is in general represented by a non-linear and non-monotonic curve in
the (T-p) phase diagram.
PMID- 25117030
TI - [Focal autoimmune pancreatitis versus pancreatic cancer: value of steroid
treatment in the diagnosis].
AB - BACKGROUND: The differential diagnosis of pancreatic cancer and focal forms of
autoimmune pancreatitis is complicated since serological tests, IgG4 and CA 19-9
have a low sensibility and specificity. CT scan and magnetic resonance imaging
provide clear differentiation in the majority, but not in all cases.
Endosonography is the most precise diagnostic procedure and allows to obtain
samples for cytology or even histological studies. AIM: To report the experience
with 18 cases of focal autoimmune pancreatitis and three cases of pancreatic
cancer. MATERIAL AND METHODS: Review of medical records of 18 patients with focal
autoimmune pancreatitis and 3 cases of pancreatic cancer. RESULTS: The eighteen
patients with focal autoimmune pancreatitis were treated with prednisone 0.5
mg/kg/day obtaining a complete clinical and morphological recovery in all.
However, 3 had a relapse and one was operated. During follow up, none has
developed a pancreatic cancer. The 3 patients with pancreatic cancer did not
respond to steroidal treatment. CONCLUSIONS: The quick and dramatic response to
steroids of autoimmune pancreatitis, may be useful and is recommended for the
differential diagnosis with pancreatic cancer.
PMID- 25117029
TI - Alcohol expectancies in childhood: change with the onset of drinking and ability
to predict adolescent drunkenness and binge drinking.
AB - AIMS: We examined the relationship between alcohol expectancies in childhood and
onset of drinking, binge drinking and drunkenness in adolescence and the
influence of drinking onset on expectancy development. DESIGN: A prospective,
longitudinal study of children assessed for alcohol expectancies and drinking at
four time-points between ages 6 and 17 years. SETTING: Community study of
families at high risk for alcoholism conducted in a four-county area in the
Midwestern United States. PARTICIPANTS: The study involved 614 children; 460 were
children of alcoholics and 70% were male. MEASUREMENTS: Expectancies about
alcohol effects were measured using the Beverage Opinion Questionnaire and
child's drinking by the Drinking and Drug History-Youth Form. FINDINGS: Partial
factor invariance was found for expectancy factors from ages 6 to 17 years.
Survival analysis showed that social/relaxation expectancies in childhood
predicted time to onset of binge drinking and first time drunk (Wald chi(2) , 1
d.f. = 3.8, P = 0.05 and 5.0, P < 0.05, respectively). The reciprocal effect was
also present; when adolescents began drinking, there was an increase in
social/relaxation expectancy and a concomitant increase in slope of the
expectancy changes lasting throughout adolescence. CONCLUSIONS: A reciprocal
relationship exists between childhood alcohol expectancies and the development of
alcohol involvement. Higher expectancies for positive effects predict earlier
onset of problem drinking. Onset of use, in turn, predicts an increase in rate of
development of positive expectancies.
PMID- 25117031
TI - [Factors associated with health promoting behaviors among Chilean adolescents].
AB - BACKGROUND: Health-promoting behaviors are important to prevent diseases and
prolong life in the population. People develop these behaviors throughout life.
However, better benefits for health are obtained with an early development. AIM:
To determine the prevalence of health-promoting behaviors among early adolescents
and its associated factors. MATERIAL AND METHODS: Cross-sectional survey
performed in 1,465 students of high, medium and low socio-economic status,
attending fifth to eighth grades of schools located in a small Chilean city.
Participants answered a questionnaire that gathered information about frequency
of health-promoting behaviors such as health responsibility and nutrition,
physical exercise and stress management, life appreciation, social support and
different personal, school and familial factors. RESULTS: A higher frequency of
health-promoting behaviors was associated with better academic achievement,
better school commitment, and higher perception of school membership. It also was
associated with a better perception of health status and a higher conformity with
physical appearance. CONCLUSIONS: Health promoting behaviors in these children
are related to a better academic achievement and a higher integration with school
environment.
PMID- 25117033
TI - [Effects of education and strength training on functional tests among older
people with osteoarthritis].
AB - BACKGROUND: Hip and knee osteoarthritis are important causes of pain and
disability among older people. Education and strength training can alleviate
symptoms and avoid functional deterioration. AIM: To assess muscle strength, fall
risk and quality of life of older people with osteoarthritis and the effects of
physiotherapy education and strength training on these variables. MATERIAL AND
METHODS: Thirty participants aged 78 +/- 5 years (63% women) were randomly
assigned to receive physiotherapy (Controls), physiotherapy plus education (Group
1) and physiotherapy plus strength training (group 2). At baseline and after 16
weeks of intervention, patients were evaluated with the Senior Fitness Test,
Timed Up and Go and Quality of Life score short form (SF-36). RESULTS: During the
intervention period, Senior Fitness Test and Timed Up and Go scores improved in
all groups and SF-36 did not change. The improvement in Senior Fitness Test and
Timed Up and Go was more marked in Groups 1 and 2 than in the control group.
CONCLUSIONS: Education and strength training improve functional tests among older
people with osteoarthritis.
PMID- 25117032
TI - [Survival of patients with metastatic breast cancer according to pathological
types of tumors].
AB - BACKGROUND: The prognosis of breast cancer (BC) is in part determined by the
stage at diagnosis and its pathological characteristics. AIM: To evaluate the
association between survival of women with metastatic breast cancer and
pathological features of the tumor. PATIENTS AND METHODS: We obtained clinical
and pathological data from patients diagnosed with a metastatic BC between 1999
and 2013. The expression of estrogen (ER) and progesterone (PR) receptors and
human epidermal growth factor receptor 2 (HER2) was determined by
immunohistochemistry. Clinicopathological subtypes were defined as: Luminal A: ER
or PR positive, HER2 negative, histological grade (HG) 1 or 2; Luminal B: ER or
PR positive, HER2 negative or positive or HG 3; triple negative (TN): ER, PR and
HER2 negative, independent of the HG, positive HER2: ER, PR negative and HER2
positive, independent of HG. We analyzed survival based on these subtypes.
RESULTS: We identified 54 patients aged 24 to 85 years, with metastatic BC at
diagnosis. Seventy five percent had luminal tumors; 19.6% HER2 positive and 7.8%
were TN. In 61% of evaluable tumors, HG was classified as 3. The frequency of
HER2 positive and high HG tumors was greater in these patients with metastatic BC
than in a non-metastatic local BC cohort. Survival was higher among patients with
Luminal tumors than in women with non-Luminal cancer (56.4 and 11.4 months,
respectively, p = 0.04). CONCLUSIONS: Patients with metastatic BC at diagnosis
often had HER2 positive tumors and high HG. As in other studies, ER positive
tumors had a better survival.
PMID- 25117034
TI - [Exposure to occupational biological risks: experience of a toxicology
information center].
AB - BACKGROUND: Exposure to Biological Agents during work is an emergent type of
occupational risk. AIM: To characterize occupational biological risk exposure
among Chilean workers which have been registered by the Toxicology Information
Center, between January 2006 and December 2009. MATERIAL AND METHODS: All
incoming calls reporting exposure to biological agents during the studied period
were analyzed. The information obtained from the caller was registered using the
Communication Record Instrument of the WHO International Programme on Chemical
Safety (IPCS INTOX). RESULTS: In the studied period, 77 calls were received. The
mean age of exposed patients was 35 +/- 15 years and 57% of them were females.
The most common involved agents were vaccines for veterinary use (42%) followed
by Loxosceles laeta bites in 16%. The main routes of exposure were injections,
cuts and needle stick injuries in 39% and stings and bites in 38%. The highest
exposure rates were observed in Southern Chile due to self-inoculation of
veterinary vaccines used in the salmon industry (22.7/100.000 actual workers).
Fifty-eight percent of calls were from health care workers, and 51% of them were
from health care facilities. Sixty percent of exposures occurred during summer
and spring. There was a fourfold higher risk of calls involving women exposed to
bites or stings (odds ratio (OR) 4.5 (CI95 1.5-13.9, p < 0.01). Men had a
fourfold higher risk of being exposed to vaccines or medications for veterinary
use (OR 4.2, CI95 1.4-12.6 p < 0.01). CONCLUSIONS: Most calls involving an
exposure to a biological agent were caused by self-inoculation of veterinary
medications.
PMID- 25117035
TI - [Association between psychological stress and metabolic control in patients with
type 1 diabetes mellitus].
AB - BACKGROUND: An association between psychological stress and metabolic control can
occur in patients with diabetes. AIM: To determine the longitudinal association
between different psychological stress domains (emotional burden, physician
related distress, regimen-related distress, diabetes-related interpersonal
distress) and metabolic control of adolescents with Type 1 diabetes. MATERIAL AND
METHODS: An intentional sample of 20 Type 1 diabetic adolescents aged 15 +/- 4
years was followed-up for one year. Three HbA1c determinations were performed and
a stress self-report was obtained with the Polonsky' Diabetes Distress Scale.
RESULTS: Several analyses were conducted using growth curve modeling. The first
model included the HbA1c measures, the time term (coded as 0, 1, 2) and several
covariates (age, years living with type 1 diabetes mellitus, sex, and physical
activity). An overall negative linear trend was found for HbA1c. Subsequent
models added the stress domains finding that high levels of emotional burden and
regimen related-distress were associated with higher HbA1c levels across all
exams. A marginal association was found between diabetes-related interpersonal
distress and HbA1c. CONCLUSIONS: Stress levels in type 1 diabetic adolescents
deserve attention. Different psychological stress factors predicting metabolic
control trajectories in type 1 diabetic adolescents were found.
PMID- 25117036
TI - [Eight weeks of combined high intensity intermittent exercise normalized altered
metabolic parameters in women].
AB - BACKGROUND: Short term physical training programs may improve insulin resistance
and hyperglycemia. AIM: To assess the effects of eight weeks of combined exercise
program on serum lipids and glycemic level in women with hyperglycemia and
hypercholesterolemia. PATIENTS AND METHODS: Ten healthy women, nine women with
hyperglycemia, ten with hypercholesterolemia and nine with
hyperglycemia/hypercholesterolemia were studied. Participants were subjected to
eight weeks into a program of combined physical exercise (high intensity interval
+ resistance training). RESULTS: Fasting glycemia decreased by 12 and 14% in
hyperglycemic and hyperglycemic/hypercholesterolemic participants, respectively.
Serum insulin decreased in all groups in a range from 27 to 37%. HOMA IR for
insulin resistance decreased similarly. A significant decrease in TC and TG was
observed only in those altered baseline subjects. CONCLUSIONS: Eight weeks of
combined physical exercise had a favorable effect on insulin resistance in this
group of women.
PMID- 25117037
TI - [Cardiovascular risk factors among males in 1989 and 2011-12 in a southern
Chilean city].
AB - BACKGROUND: A successful cardiovascular prevention program should induce a
reduction of risk factors along time. AIM: To assess changes in cardiovascular
risk factors among males aged between 35 and 65 years living in Southern Chile.
MATERIAL AND METHODS: The results of two cross sectional household surveys, with
a probability sampling stratified by socioeconomic status, were analyzed. Two
hundred males were evaluated in 1989 and 800 in 2011-12, paired by age for
selection. RESULTS: In the second survey, a mean weight increase of 4.5 kg was
recorded. Body mass index increased from 27.1 to 28.6 kg/m(2) (p < 0.01),
especially in men younger than 45 years old. No changes in smoking prevalence
were observed. The prevalence of hypertension and hypertensive patients in
treatment increased from 32.7 to 38.1% and from 17 to 33%, respectively. The
number of treated hypertensive patients with a well-controlled blood pressure did
not change significantly. In 1989 and 2011-12, mean total cholesterol values were
192 and 201 mg/dl respectively (p < 0.01). The figures for mean non-HDL
cholesterol were 152 and 160 mg/dl (p = 0.03). The frequency of people with total
cholesterol over 240 mg/dl or using statins increased from 15 to 25% (p < 0.01).
The estimated 10 years risk of myocardial infarction and coronary death using
Framingham tables was 9,0 in both periods (p = 0.95). CONCLUSIONS: In a 22 years
period an increase in the prevalence of obesity and elevated total cholesterol
was observed. There was a higher proportion of individuals treated for
hypertension and dyslipidemia, but without reduction in the estimated
cardiovascular risk.
PMID- 25117038
TI - [Analysis of the main ethical conflicts in the 2008 declaration of Helsinki and
the proposed changes in the new version].
AB - The Declaration of Helsinki (DoH) of the World Medical Association is the basis
of the rules governing research on human beings. The latest version (enacted in
Korea, 2008) has been a source of ethical discussions, particularly regarding the
use of placebos, the measures to assure the access of study subjects to
interventions identified as beneficial once the study has ended, and the need of
a better protection of potentially vulnerable groups. These issues led to draft a
revised version, that was approved in 2013. In this paper, we present an ethical
analysis of the main changes contained in the DoH, including the proposed changes
in the new version, referring, when appropriate, to relevant Chilean laws
governing research on human subjects. In our opinion, the 2008 DoH contains
significant imprecisions on some of these issues, making a new version of the
declaration necessary to fully protect subjects participating in biomedical
research, as stated by the new version approved in 2013.
PMID- 25117039
TI - [Postoperative delirium among older people].
AB - Delirium (acute confusional state) is a common and disabling complication among
surgical older people. It is often underdiagnosed and undertreated. Its incidence
varies by type of intervention and it is associated with several complications
such as functional impairment, cognitive dysfunction, prolonged hospitalization
and institutionalization. These increase hospitalization costs and the risk of
death. There are precipitating and predisposing risk factors, which increase the
susceptibility for postoperative delirium. This condition should be considered as
a syndrome of epidemiological importance, which needs to be prevented or treated
in a timely manner through a multidisciplinary intervention. The perioperative
care of elderly patients involves different medical specialties and is a subject
of general knowledge.
PMID- 25117040
TI - [Use of Internet for mental health programs aimed at adolescents].
AB - BACKGROUND: The widespread use of INTERNET by adolescents, renders it a simple
and accessible means for health care campaigns Aim: To perform a systematic
review of ISI publications about INTERNET use for adolescent mental health
prevention, detection, treatment or follow up. MATERIAL AND METHODS: Systematic
reviews, meta analyses and controlled clinical trials in all languages were
searched. Manuscripts without an abstract or only publishing the study design
were excluded. All selected articles were critically read. RESULTS: One hundred
and five papers were found and 61 were excluded because they did not address the
research question. Of the resting 44, only six complied with the search criteria
among then, 3 articles correspond to systematic reviews addressing early
intervention programs and mental hearth treatment based on Internet; the other 3
articles correspond to controlled clinical trials addressing treatment
interventions of anxiety and depression and 1 address on depression prevention
program. CONCLUSIONS: INTERNET facilitates the application of mental health
promotion, prevention and intervention among adolescents. However the resource is
still underused.
PMID- 25117041
TI - [A proposal for the definitive reform of the private health insurance system in
Chile].
AB - Private health insurance should be able to provide coverage to people considered
as high risk, such as women and the elderly. The only way to do that is to
organize implicit or explicit cross-subsidies from low to high-risk individuals.
This paper examines how European private health insurance companies introduced
regulatory measures that could be introduced in Chile such as open enrollment,
community-rated premiums, lifetime coverage, a package of minimum benefits and a
risk equalization scheme.
PMID- 25117042
TI - [Respecting patient intimacy].
AB - Transparency as a general rule for all our professional acts casts doubts about
the statement of the Hippocratic Oath that says "Whatever I see or hear in the
lives of my patients, I will keep secret, as considering all such things to be
private". Medical secrecy protects the intimacy of patients, who reveal to their
physicians their most hidden secrets aiming to recover their health. Therefore,
physicians should receive those secrets with reverence and care, as servers and
not as their owners. The values associated with the respect for personal intimacy
are the anthropological basis of medical confidentiality. A medical act is
performed by definition between two equally honorable individuals. Therefore, the
professional honors the trust of his patient, maintaining strict confidence of
what is revealed. Therefore, medical secrecy must be strengthened rather than
weakened, pursuing common wealth and dignity.
PMID- 25117043
TI - The role of the psychiatrist in obtaining informed consent from patients with
somatic and mental comorbidity: Report of one case.
AB - The nature of mental disorders, the attitudes and prejudices of the social
community towards psychiatric patients, the behavior and treatment of mental
patients, all bring about numerous dilemmas and prejudices. When a patient is
diagnosed with a mental disorder, he may suffer restrictions in the field of
general human rights. However, the biggest problems in clinical practice occur in
the treatment of patients who, besides their mental disorder also have a somatic
disease. We report a 56-years-old female with a severe renal failure who refused
to undergo dialysis. Following the patient's refusal to sign an informed consent,
a psychiatrist was called in for consultation and diagnosed an acute psychotic
reaction. To manage the delusions and acute psychotic reactions, risperidone in
the dose of 2 mg was started. After 22 days, the patient still had marked
psychotic symptoms. A psychiatrist, a nephrologist and an anesthesiologist, in
the presence of the spouse on the grounds of her life-threatening condition,
decided to apply the necessary medical procedures even without the patient's
consent. A day after the start of dialysis the patient still had delusional
ideas, but without the presence of anxiety, and the patient no longer offered
resistance to dialysis. Four days after the first dialysis, the patient was calm,
had vague memories about the entire previous period, and signed the informed
consent concerning her further treatment.
PMID- 25117044
TI - [Sustained hematologic response in chronic eosinophilic leukemia with low dose
imatinib. Report of one case].
AB - We report a 58 year-old-man without comorbid conditions, with a history of two
months of weight loss, malaise and headache. His initial laboratory analysis
showed leukocytosis of 16,100/mL with 65% eosinophils and an absolute eosinophil
count of 10,465/mL. Both bone marrow biopsy and aspirate showed infiltration by
mature appearing eosinophils. Treatment was started with hydroxyurea, associated
with prednisone without satisfactory decrease in the eosinophil count. Polymerase
chain reaction showed the presence of the gene fusion product FIP1L1/PDGFRA.
Imatinib therapy was initiated, resulting in a rapid and progressive reduction in
the absolute eosinophil count, with normalization at the second week of
treatment. The incidence of the myeloproliferative variant causing
hypereosinophilic syndrome is rare. However, the dramatic response to imatinib
emphasizes the need to study the presence of the fusion product FIP1L1/PDGFRA in
all patients with eosinophilia of unknown etiology.
PMID- 25117045
TI - [First successful bridge to cardiac transplantation in Chile using the Heart Mate
II device. Report of one case].
AB - Implantable ventricular assist devices are an effective treatment option for end
stage heart failure patients as a bridge to cardiac transplantation, to improve
the clinical condition and organ function allowing discharge from the hospital to
await for transplantation. The second alternative is to use the device as
destination therapy for patients with contraindications for cardiac
transplantation, in whom it is maintained indefinitely. We report a 43-year-old
patient, with a dilated cardiomyopathy, severe left ventricular dysfunction and
advanced heart failure. A ventricular assist device Heart Mate II(c), as a bridge
to transplantation, was implanted to the patient in the United States. It was
explanted for the first time in Chile at the National Thorax Institute. Heart
transplantation was performed using the bicaval technique. Induction of
immunosuppression was done with basiliximab. Generic immunosuppression was
carried out with cyclosporine, mycophenolate mofetil and prednisone.
Postoperatively the patient evolved with right femoral vein thrombosis in the
femoral cannulation site, phlegmasia alba dolens, rhabdomyolysis, oliguric acute
renal failure, which required renal replacement therapy, severe shock, with high
requirements of vasoactive drugs and need for mechanical ventilation. He required
a reoperation for hemothorax and had an Enterobacter pneumonia. After a period of
serious illness, he began a gradual recovery and was discharged from the hospital
after 58 days. After two years, he remains in functional class I, with a normal
graft function.
PMID- 25117046
TI - [Granulomatous appendicitis caused by sarcoidosis: report of one case].
AB - Granulomatous appendicitis is uncommon and can be caused by Crohn's disease,
foreign body reactions, infections or sarcoidosis. We report a 26-year-old female
consulting in the emergency room for pain in the right lower abdomen. She was
released with analgesics and consulted 14 days later for the same pain. This time
she was operated with the preoperative diagnosis of appendicitis. The
pathological study of the surgical piece was compatible with a granulomatous
appendicitis caused by sarcoidosis.
PMID- 25117047
TI - [Frederic Chopin (1810-1849), and his disease].
AB - Frederic Chopin - a great Polish composer and pianist-suffered from a chronic
disease. Both during his life and after his death, physicians disagreed on
Chopin's diagnosis. His contemporaries accepted the diagnosis of tuberculosis, a
common disease in the 18th century. Description of new clinical entities provoked
new dilemmas in the 21th century. Although other alternative diagnoses to
tuberculosis have emerged, such as cystic fibrosis or alpha-1 antitrypsin
deficiency, we still sustain that the first diagnosis is the most probable. In
this paper we report F. Chopin's case history and discuss cons and pros for
different diseases as the cause of F. Chopin's suffering and death.
PMID- 25117050
TI - [Environmental effect on the incidence of Hantavirus cardiopulmonary syndrome in
Chile].
PMID- 25117051
TI - [Centenary of the School of Public Health at Harvard University: Career and
prestige].
PMID- 25117052
TI - [When you visit a doctor, do you hope that the doctor gives you one hour or only
a few minutes?].
PMID- 25117053
TI - Bacterial community affects toxin production by Gymnodinium catenatum.
AB - The paralytic shellfish toxin (PST)-producing dinoflagellate Gymnodinium
catenatum grows in association with a complex marine bacterial community that is
both essential for growth and can alter culture growth dynamics. Using a
bacterial community replacement approach, we examined the intracellular PST
content, production rate, and profile of G. catenatum cultures grown with
bacterial communities of differing complexity and composition. Clonal offspring
were established from surface-sterilized resting cysts (produced by sexual
crosses of strain GCDE06 and strain GCLV01) and grown with: 1) complex bacterial
communities derived from each of the two parent cultures; 2) simplified bacterial
communities composed of the G. catenatum-associated bacteria Marinobacter sp.
strain DG879 or Alcanivorax sp. strain DG881; 3) a complex bacterial community
associated with an untreated, unsterilized sexual cross of the parents. Toxin
content (STX-equivalent per cell) of clonal offspring (134-197 fmol STX cell(-1))
was similar to the parent cultures (169-206 fmol STX cell(-1)), however cultures
grown with single bacterial types contained less toxin (134-146 fmol STX cell(
1)) than offspring or parent cultures grown with more complex mixed bacterial
communities (152-176 fmol STX cell(-1)). Specific toxin production rate (fmol STX
day(-1)) was strongly correlated with culture growth rate. Net toxin production
rate (fmol STX cell(-1) day(-1)) did not differ among treatments, however, mean
net toxin production rate of offspring was 8-fold lower than the parent cultures,
suggesting that completion of the sexual lifecycle in laboratory cultures leads
to reduced toxin production. The PST profiles of offspring cultures were most
similar to parent GCDE06 with the exception of cultures grown with Marinobacter
sp. DG879 which produced higher proportions of dcGTX2+3 and GC1+2, and lower
proportions of C1+2 and C3+4. Our data demonstrate that the bacterial community
can alter intracellular STX production of dinoflagellates. In G. catenatum the
mechanism appears likely to be due to bacterial effects on dinoflagellate
physiology rather than bacterial biotransformation of PST toxins.
PMID- 25117054
TI - A new phenyl glycoside from the aerial parts of Equisetum hyemale.
AB - A new phenyl glycoside, 2-(sophorosyl)-1-(4-hydroxyphenyl)ethanone (9), was
isolated from the ethanolic extract of the aerial parts of Equisetum hyemale L.,
together with eight known compounds (1-8). The structures of these compounds were
elucidated using a combination of spectroscopic analyses and chemical method. Of
these nine compounds, 4 and 7 showed hepatoprotective effects towards tacrine
induced cytotoxicity in Hep 3B cells with EC50 values of 42.7 +/- 1.5 and 132.6
+/- 2.8 MUM, respectively.
PMID- 25117055
TI - Weak self-interactions of globular proteins studied by small-angle X-ray
scattering and structure-based modeling.
AB - We investigate protein-protein interactions in solution by small-angle X-ray
scattering (SAXS) and theoretical modeling. The structure factor for solutions of
bovine pancreatic trypsin inhibitor (BPTI), myoglobin (Mb), and intestinal fatty
acid-binding protein (IFABP) is determined from SAXS measurements at multiple
concentrations, from Monte Carlo simulations with a coarse-grained structure
based interaction model, and from analytic approximate solutions of two idealized
colloidal interaction models without adjustable parameters. By combining these
approaches, we find that the structure factor is essentially determined by hard
core and screened electrostatic interactions. Other soft short-ranged
interactions (van der Waals and solvation-related) are either individually
insignificant or tend to cancel out. The structure factor is also not
significantly affected by charge fluctuations. For Mb and IFABP, with a small net
charge and relatively symmetric charge distribution, the structure factor is well
described by a hard-sphere model. For BPTI, with a larger net charge, screened
electrostatic repulsion is also important, but the asymmetry of the charge
distribution reduces the repulsion from that predicted by a charged hard-sphere
model with the same net charge. Such charge asymmetry may also amplify the effect
of shape asymmetry on the protein-protein potential of mean force.
PMID- 25117057
TI - Intervention synthesis: a missing link between a systematic review and practical
treatment(s).
AB - Paul Glasziou and colleagues discuss methods to guide selection of an
intervention from individual trials within a systematic review. Please see later
in the article for the Editors' Summary.
PMID- 25117059
TI - Chemical composition of essential oils and hydrosols from fresh flowers of
Cerasus subhirtella and Cerasus serrulata from East China.
AB - Essential oils and hydrosols from fresh flowers of Cerasus subhirtella (Miq.)
Sok. and Cerasusserrulata (Lindl.) London from East China were analysed by gas
chromatography and gas chromatography-mass spectrometry for the first time. The
major components of the essential oils from C. subhirtella and C.serrulata were
benzaldehyde (31.2% and 42.1%, respectively), tricosane (23.1% and 27.7%,
respectively) and pentacosane (23.2% and 19.0%, respectively). The main
constituents of the hydrosol volatiles from C. subhirtella and C.serrulata were
benzaldehyde (67.5% and 64.3%, respectively) and mandelonitrile (12.5% and 12.4%,
respectively). Benzaldehyde was the key component of the essential oils, while
benzaldehyde as well as mandelonitrile was the principal compound of the
hydrosols.
PMID- 25117060
TI - Mesoscopic structuring and dynamics of alcohol/water solutions probed by
terahertz time-domain spectroscopy and pulsed field gradient nuclear magnetic
resonance.
AB - Terahertz and PFG-NMR techniques are used to explore transitions in the
structuring of binary alcohol/water mixtures. Three critical alcohol mole
fractions (x1, x2, x3) are identified: methanol (10, 30, 70 mol %), ethanol (7,
15, 60 mol %), 1-propanol (2, 10, 50 mol %), and 2-propanol (2, 10, 50 mol %).
Above compositions of x1 no isolated alcohol molecules exist, and below x1 the
formation of large hydration shells around the hydrophobic moieties of the
alcohol is favored. The maximum number of water molecules, N0, in the hydration
shell surrounding a single alcohol molecule increases with the length of the
carbon chain of the alcohol. At x2 the greatest nonideality of the liquid
structure exists with the formation of extended hydrogen bonded networks between
alcohol and water molecules. The terahertz data show the maximum absorption
relative to that predicted for an ideal mixture at that composition, while the
PFG-NMR data exhibit a minimum in the alkyl chain self-diffusivity at x2, showing
that the alcohol has reached a minimum in diffusion when this extended alcohol
water network has reached the highest degree of structuring. At x3 an equivalence
of the alkyl and alcohol hydroxyl diffusion coefficients is determined by PFG
NMR, suggesting that the molecular mobility of the alcohol molecules becomes
independent of that of the water molecules.
PMID- 25117058
TI - Aggressiveness of intensive care use among patients with lung cancer in the
Surveillance, Epidemiology, and End Results-Medicare registry.
AB - BACKGROUND: Approximately 65% of elderly patients with lung cancer who are
admitted to the ICU will die within 6 months. Efforts to improve end-of-life care
for this population must first understand the patient factors that underlie
admission to the ICU. METHODS: We performed a retrospective cohort study
examining all fee-for-service inpatient claims in the Surveillance, Epidemiology,
and End Results (SEER)-Medicare registry for elderly patients (aged > 65 years)
who had received a diagnosis of lung cancer between 1992 and 2005 and who were
hospitalized for reasons other than resection of their lung cancer. We calculated
yearly rates of ICU admission per 1,000 hospitalizations via room and board codes
or International Classification of Diseases, Ninth Revision, Clinical
Modification and diagnosis-related group codes for mechanical ventilation,
stratified the rates by receipt of mechanical ventilation and ICU type
(medical/surgical/cardiac vs intermediate), and compared these rates over time.
RESULTS: A total of 175,756 patients with lung cancer in SEER were hospitalized
for a reason other than surgical resection of their tumor during the study
period, 49,373 (28%) of whom had at least one ICU stay. The rate of ICU
admissions per 1,000 hospitalizations increased over the study period from 140.7
in 1992 to 201.7 in 2005 (P < .001). The majority of the increase in ICU
admissions (per 1,000 hospitalizations) between 1992 and 2005 occurred among
patients who were not mechanically ventilated (118.2 to 173.3, P < .001) and
among those who were in intermediate ICUs (20.0 to 61.9, P < .001), but increased
only moderately in medical/surgical/cardiac units (120.7 to 139.9, P < .001).
CONCLUSIONS: ICU admission for patients with lung cancer increased over time,
mostly among patients without mechanical ventilation who were largely cared for
in intermediate ICUs.
PMID- 25117056
TI - Thiamine Deficiency-Mediated Brain Mitochondrial Pathology in Alaskan Huskies
with Mutation in SLC19A3.1.
AB - Alaskan Husky encephalopathy (AHE(1) ) is a fatal brain disease associated with a
mutation in SLC19A3.1 (c.624insTTGC, c.625C>A). This gene encodes for a thiamine
transporter 2 with a predominately (CNS) central nervous system distribution.
Considering that brain is particularly vulnerable to thiamine deficiency because
of its reliance on thiamine pyrophosphate (TPP)-dependent metabolic pathways
involved in energy metabolism and neurotransmitter synthesis, we characterized
the impact of this mutation on thiamine status, brain bioenergetics and the
contribution of oxidative stress to this phenotype. In silico modeling of the
mutated transporter indicated a significant loss of alpha-helices resulting in a
more open protein structure suggesting an impaired thiamine transport ability.
The cerebral cortex and thalamus of affected dogs were severely deficient in TPP
dependent enzymes accompanied by decreases in mitochondrial mass and oxidative
phosphorylation (OXPHOS) capacity, and increases in oxidative stress. These
results along with the behavioral and pathological findings indicate that the
phenotype associated with AHE is consistent with a brain-specific thiamine
deficiency, leading to brain mitochondrial dysfunction and increased oxidative
stress. While some of the biochemical deficits, neurobehavior and affected brain
areas in AHE were shared by Wernicke's and Korsakoff's syndromes, several
differences were noted likely arising from a tissue-specific vs. that from a
whole-body thiamine deficiency.
PMID- 25117062
TI - Reversible cerebral periventricular white matter changes with corpus callosum
involvement in acute toluene-poisoning.
AB - Substance poisoning, such as toluene intoxication, has seldom been reported in
the relevant literature. The documented cerebral neuroimaging has mostly
described reversible symmetrical white matter changes in both the cerebral and
cerebellar hemispheres. This paper presents 2 patients with toluene poisoning,
whose brain magnetic resonance imaging studies showed a similar picture that
included extra involvement over the corpus callosum; however, such corpus
callosum involvement has never been mentioned and is quite rare in the
literature. We discussed the underlying neuropathological pathways in this
article. Hopefully, these cases will provide first-line clinicians with some
valuable information with regard to toluene intoxication and clinical
neuroimaging presentations.
PMID- 25117063
TI - Too fat, too thin: understanding bias against overweight and underweight in an
Australian female university student sample.
AB - OBJECTIVE: We compare attribution and social comparison theories as potential
explanations for attitudes towards overweight and underweight targets among
Australian university students. DESIGN: 185 female students (median age 18)
completed a measure of body image state, then read one of six vignettes,
describing a female student who was underweight, average weight or overweight,
and who did or did not have a medical condition affecting weight. Independent
variables were target weight (underweight, average-weight, overweight); weight
controllability (no information, uncontrollable); and participant body image
(higher, lower). MAIN OUTCOME MEASURES: Participants evaluated the target on six
characteristics derived from existing research on weight bias, on seven-point
Likert scales: attractive; healthy; likeable; motivated; self-disciplined; having
willpower. RESULTS: A three-way between-participants multivariate analysis of
covariance was conducted, with post hoc comparisons of significant effects.
Overweight targets were rated more negatively than average-weight and underweight
targets. Uncontrollability (medical) information produced more positive
evaluations of the overweight target, but more negative evaluations of the
underweight target. Ratings of the average-weight target were not influenced by
uncontrollability information. Participant body image state had no significant
effects. CONCLUSION: Results provided partial support for attribution theory, but
not for social comparison theory, as an explanation of weight bias.
PMID- 25117064
TI - Reverse-phase protein array for prediction of patients at low risk of developing
bone metastasis from breast cancer.
AB - BACKGROUND: A biomarker that predicts bone metastasis based on a protein
laboratory assay has not been demonstrated. Reverse-phase protein array (RPPA)
enables quantification of total and phosphorylated proteins, providing
information about their functional status. The aim of this study was to identify
bone-metastasis-related markers in patients with primary breast cancer using RPPA
analysis. PATIENTS AND METHODS: Tumor samples were obtained from 169 patients
with primary invasive breast carcinoma who underwent surgery. The patients were
categorized by whether they developed breast cancer bone metastasis (BCBM) during
follow-up. Clinical characteristics and protein expression by RPPA were compared
and verified by leave-one-out cross-validation. RESULTS: Lymph node status (p =
.023) and expression level of 22 proteins by RPPA were significantly correlated
with BCBM in logistic regression analysis. These variables were used to build a
logistic regression model. After filtering the variables through a stepwise
algorithm, the final model, consisting of 8 proteins and lymph node status, had
sensitivity of 30.0%, specificity of 90.5%, positive predictive value of 30.0%,
and negative predictive value of 90.5% in the cross-validation. Most of the
identified proteins were associated with cell cycle or signal transduction (CDK2,
CDKN1A, Rb1, Src, phosphorylated-ribosomal S6 kinase, HER2, BCL11A, and MYH11).
CONCLUSION: Our validated model, in which the primary tumor is tested with RPPA,
can predict patients who are at low risk of developing BCBM and thus who likely
would not benefit from receiving a bisphosphonate in the adjuvant setting.
Clinical trials excluding these patients have the potential to clarify the
benefit of bisphosphonates in the adjuvant setting.
PMID- 25117066
TI - A community-based multicenter trial of pharmacokinetically guided 5-fluorouracil
dosing for personalized colorectal cancer therapy.
AB - BACKGROUND: Pharmacokinetically guided (PK-guided) versus body surface area-based
5-fluorouracil (5-FU) dosing results in higher response rates and better
tolerability. A paucity of data exists on PK-guided 5-FU dosing in the community
setting. PATIENTS AND METHODS: Seventy colorectal cancer patients, from one
academic and five community cancer centers, received the mFOLFOX6 regimen (5-FU
2,400 mg/m(2) over 46 hours every 2 weeks) with or without bevacizumab at cycle
1. The 5-FU continuous-infusion dose was adjusted for cycles 2-4 using a PK
guided algorithm to achieve a literature-based target area under the
concentration-time curve (AUC). The primary objective was to demonstrate that PK
guided 5-FU dosing improves the ability to achieve a target AUC within four
cycles of therapy. The secondary objective was to demonstrate reduced incidence
of 5-FU-related toxicities. RESULTS: At cycles 1 and 4, 27.7% and 46.8% of
patients achieved the target AUC (20-25 mg * hour/L), respectively (odds ratio
[OR]: 2.20; p = .046). Significantly more patients were within range at cycle 4
compared with a literature rate of 20% (p < .0001). Patients had significantly
higher odds of not being underdosed at cycle 4 versus cycle 1 (OR: 2.29; p =
.037). The odds of a patient being within range increased by 30% at each
subsequent cycle (OR: 1.30; p = .03). Less grade 3/4 mucositis and diarrhea were
observed compared with historical data (1.9% vs 16% and 5.6% vs 12%,
respectively); however, rates of grade 3/4 neutropenia were similar (33% vs 25%
50%). CONCLUSION: PK-guided 5-FU dosing resulted in significantly fewer
underdosed patients and less gastrointestinal toxicity and allows for the
application of personalized colorectal cancer therapy in the community setting.
PMID- 25117065
TI - Real-world study of everolimus in advanced progressive neuroendocrine tumors.
AB - Everolimus is a valid therapeutic option for neuroendocrine tumors (NETs);
however, data in a real-world setting outside regulatory trials are sparse. The
aim of this study was to determine everolimus tolerability and efficacy, in
relation to previous treatments, in a compassionate use program. A total of 169
patients with advanced progressive NETs treated with everolimus were enrolled,
including 85 with pancreatic NETs (pNETs) and 84 with nonpancreatic NETs (non
pNETs). Previous treatments included somatostatin analogs (92.9%), peptide
receptor radionuclide therapy (PRRT; 50.3%), chemotherapy (49.7%), and PRRT and
chemotherapy (22.8%). Overall, 85.2% of patients experienced adverse events
(AEs), which were severe (grade 3-4) in 46.1%. The most frequent severe AEs were
pneumonitis (8.3%), thrombocytopenia (7.7%), anemia (5.3%), and renal failure
(3.5%). In patients previously treated with PRRT and chemotherapy, a 12-fold
increased risk for severe toxicity was observed, with grade 3-4 AEs reported in
86.8% (vs. 34.3% in other patients). In addition, 63.3% of patients required
temporarily everolimus discontinuation due to toxicity. Overall, 27.8% of
patients died during a median follow-up of 12 months. Median progression-free
survival (PFS) and overall survival (OS) were 12 months and 32 months,
respectively. Similar disease control rates, PFS, and OS were reported in pNETs
and non-pNETs. In the real-world setting, everolimus is safe and effective for
the treatment of NETs of different origins. Higher severe toxicity occurred in
patients previously treated with systemic chemotherapy and PRRT. This finding
prompts caution when using this drug in pretreated patients and raises the issue
of planning for everolimus before PRRT and chemotherapy in the therapeutic
algorithm for advanced NETs.
PMID- 25117067
TI - The association of hospital spending intensity and cancer outcomes: a population
based study in an Asian country.
AB - BACKGROUND: Different results are reported for the relationship between regional
variation in medical spending and disease prognosis for acute illness and for
cancer. Our objective was to investigate the association between hospital medical
care spending intensity and mortality rates in cancer patients. METHODS: A total
of 80,597 patients with incident cancer diagnosed in 2002 were identified from
the National Health Insurance Research Database of Taiwan, Republic of China. The
Cox proportional hazards model was used to compare the 5-year survival rates of
patients treated at hospitals with different spending intensities after adjusting
for possible confounding and risk factors. RESULTS: After adjustment for patient
characteristics, treatment modality, and hospital volume, an association was
found between lower hospital spending intensity and poorer survival rates. The 5
year survival rate expressed by hazard ratios was 1.36 (95% confidence interval
[CI]: 1.30-1.43, p < .001) for colorectal cancer, 1.18 (95% CI: 1.08-1.29, p <
.001) for lung cancer, 1.13 (95% CI: 1.05-1.22, p = .002) for hepatoma, 1.16 (95%
CI: 1.07-1.26, p < .001) for breast cancer, and 1.23 (95% CI: 1.10-1.39, p =
.001) for prostate cancer. CONCLUSION: Our preliminary findings indicate that
higher hospital spending intensity was associated with lower mortality rates in
patients being treated for lung cancer, breast cancer, colorectal cancer,
prostate cancer, hepatoma, or head and neck cancer. The cancer stages were
unavailable in this series, and more research linked with the primary data may be
necessary to clearly address this issue.
PMID- 25117069
TI - TGF-beta1 mediates estrogen receptor-induced epithelial-to-mesenchymal transition
in some tumor lines.
AB - More and more studies have reported that epithelial-mesenchymal transition (EMT)
involved in the process of cancer development and progression occurs. The EMT
also plays an important role in the movement and transfer of the tumors.
Transforming growth factor-beta (TGF-beta) could induce the EMT in some cancer
cell types. However, the mechanism underlying this transition process has also
not been entirely clarified. In this study, the results indicated that TGF-beta1
mediated EMT in the tumor was associated with the estrogen receptor (ER). The
decreased expression of vimentin and snail resulted in the decrease of the ER
expression by small interfering RNA-mediated silencing and preventing the TGF
beta-induced EMT. In conclusion, our results indicated that TGF-beta1 is an
estrogen receptor signaling and essential novel downstream targets and could act
as an important factor in the TGF-beta-induced EMT.
PMID- 25117070
TI - MicroRNA-320a suppresses in GBM patients and modulates glioma cell functions by
targeting IGF-1R.
AB - Glioblastoma (GBM) is the most aggressive and malignant glioma. Currently, a few
modern surgical and medical therapeutic strategies are applied for GBM, but the
prognosis of GBM patients remains poor, and the average median survival time is
only 14.6 months. In this study, we for the first time found that the levels of
miR-320a were decreased in both GBM patients and glioma cells. In GBM patients,
elevated miR-320a expression was associated with better prognosis. In addition,
insulin-like growth factor-1 receptor (IGF-1R) was identified as a key direct
target of miR-320a. Overexpression of miR-320a led to the inhibition of cell
proliferation, migration, invasion, as well as tumorigenesis by targeting IGF-1R,
and thus regulated the signaling pathways downstream, including PI3K/AKT and
MAPK/ERK. In tumor orthotopic xenograft experiment, the tumor growth was
depressed and survival time of mice model was prolonged when miR-320a was
overexpressed. Therefore, our results suggested that miR-320a could suppress
tumor development and growth by targeting IGF-1R, and miR-320a might serve as a
new effective target for anti-cancer therapy strategies.
PMID- 25117072
TI - Genetic variations of CAV1 gene contribute to HCC risk: a case-control study.
AB - Hepatocellular carcinoma (HCC) is the sixth common cancer and the third common
cause of cancer mortality worldwide. However, the exact molecular mechanism of
HCC remains uncertain. Caveolin-1 (CAV1) is the main protein in the caveolin
family and plays an important role in tumorigenesis signaling. However, the
contribution of CAV1 genetic variants to HCC is still unknown. The purpose of
this study was to evaluate the association between the tagSNPs of the CAV1 gene
and HCC risk. In this case-control study, we enrolled 1,000 HCC patients and
1,000 cancer-free controls, which were frequency-matched by age, gender, and HBV
infection status. We found that CAV1 rs729949 was statistically associated with
increased risk of HCC (odds ratio (OR) = 1.28; 95% confidence interval (CI), 1.11
1.48; P = 8.53 * 10(-4)), even after Bonferroni correction (P = 5.97 * 10(-3));
the expression levels of CAV1 in cancer tissues were significantly lower than
those in adjacent normal tissues (P = 0.012). We also detected a significant
association for CAV1 rs3807989 under the log-additive model (OR = 0.85; 95% CI,
0.74-0.98; P = 0.026). Significant associations were also detected for CAV1
rs6466583 (GG vs AA: OR = 2.53; 95% CI, 1.24-5.17; P = 0.011) and CAV1 rs3807986
(AG vs AA: OR = 3.16; 95% CI, 1.68-5.91; P = 3.36 * 10(-4)) among genotype
comparisons. These findings indicated that genetic variants n CAV1 might
contribute to HCC susceptibility.
PMID- 25117071
TI - Multifunctional CD40L: pro- and anti-neoplastic activity.
AB - The CD40 ligand is a type I transmembrane protein that belongs to a tumor
necrosis factor (TNF) superfamily. It is present not only on the surface of
activated CD4+ T cells, B cells, blood platelets, monocytes, and natural killer
(NK) cells but also on cancer cells. The receptor for ligand is constitutively
expressed on cells, TNF family protein: CD40. The role of the CD40/CD40L pathway
in the induction of body immunity, in inflammation, or in hemostasis has been
well documented, whereas its involvement in neoplastic disease is still under
investigation. CD40L ligand may potentiate apoptosis of tumor cells by activation
of nuclear factor-kappaB (NF-kappaB), AP-1, CD95, or caspase-depended pathways
and stimulate host immunity to defend against cancer. Although CD40L has a major
contribution to anti-cancer activity, many reports point at its ambivalent
nature. CD40L enhance release of strongly pro-angiogenic factor, vascular
endothelial growth factor (VEGF), and activator of coagulation, TF, the level of
which is correlated with tumor metastasis. CD40L involvement in the inhibition of
tumor progression has led to the emergence of not only therapy using recombinant
forms of the ligand and vaccines in the treatment of cancer but also therapy
consisting of inhibiting platelets-main source of CD40L. This article is a review
of studies on the ambivalent role of CD40L in neoplastic diseases.
PMID- 25117068
TI - Advanced pancreatic cancer: flourishing novel approaches in the era of biological
therapy.
AB - The progress in the development of systemic treatment for advanced pancreatic
cancer (APC) has been slow. The mainstream treatment remains using chemotherapy
including gemcitabine, FOLFIRINOX, and nab-paclitaxel. Erlotinib is the only
approved biological therapy with marginal benefit. Studies of agents targeting
epidermal growth factor receptor, angiogenesis, and RAS signaling have not been
satisfying, and the usefulness of targeted therapy in APC is uncertain.
Understanding in molecular processes and tumor biology has opened the door for
new treatment strategies such as targeting insulin-like growth factor 1 receptor,
transforming growth factor beta, phosphoinositide 3-kinase/AKT/mammalian target
of rapamycin pathway, and Notch pathway. New directions also include the upcoming
immunotherapy and many novel agents that act on the microenvironment. The
practice of personalized medicine using predictive biomarkers and
pharmacogenomics signatures may also enhance the effectiveness of existing
treatment. Future treatment approaches may involve comprehensive genomic
assessment of tumor and integrated combinations of multiple agents to overcome
treatment resistance.
PMID- 25117073
TI - Expression of HSPA2 in human hepatocellular carcinoma and its clinical
significance.
AB - Hepatocellular carcinoma (HCC) remains one of the most common cancers worldwide.
HSPA2 has been highlighted as an important marker in many types of cancers.
However, little is known about the role of HSPA2 in HCC. The objective of the
current study was to investigate the expression pattern and clinicopathological
significance of HSPA2 in patients with HCC. Quantitative reverse-transcriptase
ploymerase chain reaction (qRT-PCR) was applied to examine HSPA2 messenger RNA
(mRNA) expression in 52 pairs of HCC tissues and adjacent noncancerous tissues.
Immunohistochemistry (IHC) was performed to examine HSPA2 protein expression in
paraffin-embedded tissues from 119 HCC patients. Statistical analyses were
applied to evaluate the diagnostic value and associations of HSPA2 expression
with clinicopathological characteristics. We identified abnormally elevated mRNA
expression of HSPA2 in HCC tissues compared to paired adjacent noncancerous
tissues (P < 0.001). Clinicopathological analysis showed that HSPA2 expression
was significantly correlated with tumor size (P = 0.013), histological
differentiation (P = 0.04), and tumor stage (P = 0.001). Patients with higher
HSPA2 expression had shorter overall survival time, whereas those with lower
HSPA2 expression had longer survival time. Furthermore, Cox regression analyses
showed that HSPA2 expression was an independent predictor of overall survival. In
conclusion, our findings provide evidences that positive expression of HSPA2 in
HCC may be important in the acquisition of an aggressive phenotype and it is an
independent biomarker for poor prognosis of patients with HCC.
PMID- 25117077
TI - Phantom validation of Monte Carlo modeling for noncontact depth sensitive
fluorescence measurements in an epithelial tissue model.
AB - Experimental investigation and optimization of various optical parameters in the
design of depth sensitive optical measurements in layered tissues would require a
huge amount of time and resources. A computational method to model light
transport in layered tissues using Monte Carlo simulations has been developed for
decades to reduce the cost incurred during this process. In this work, we
employed the Monte Carlo method to investigate the depth sensitivity achieved by
various illumination and detection configurations including both the traditional
cone configurations and new cone shell configurations, which are implemented by
convex or axicon lenses. Phantom experiments have been carried out to validate
the Monte Carlo modeling of fluorescence in a two-layered turbid, epithelial
tissue model. The measured fluorescence and depth sensitivity of different
illumination-detection configurations were compared with each other. The results
indicate excellent agreement between the experimental and simulation results in
the trends of fluorescence intensity and depth sensitivity. The findings of this
study and the development of the Monte Carlo method for noncontact setups provide
useful insight and assistance in the planning and optimization of optical designs
for depth sensitive fluorescence measurements.
PMID- 25117074
TI - Wnt/beta-catenin pathway in bone cancers.
AB - The Wnt signaling pathway regulates some of the crucial aspects of cellular
processes. The beta-catenin dependent Wnt signaling (Wnt/beta-catenin) pathway
controls the expression of key developmental genes, and acts as an intracellular
signal transducer. The association of Wnt/beta-catenin pathway is often reported
with different cancers. In this study, we have reviewed the association of
Wnt/beta-catenin pathway with bone cancers, focusing on carcinogenesis and
therapeutic aspects. Wnt/beta-catenin pathway is a highly complex and unique
signaling pathway, which has ability to regulate gene expression, cell invasion,
migration, proliferation, and differentiation for the initiation and progression
of bone cancers, especially osteosarcoma. Association of Wnt/beta-catenin pathway
with chondrosarcoma, Ewing's sarcoma and chondroma is also documented. Recently,
targeting Wnt/beta-catenin pathway has gained significant interests as a
potential therapeutic application for the treatment of bone cancers. Small RNA
technology to knockdown aberrant Wnt/beta-catenin or inhibition of beta-catenin
expression by natural component has shown promising effects against bone cancers.
Advances in understanding the mechanisms of Wnt signaling and new technologies
have facilitated the discovery of agents that can target and regulate Wnt/beta
catenin signaling pathway, and these may provide a basement for the innovative
therapeutic approaches in the treatment of bone cancers.
PMID- 25117075
TI - Polymorphism in interleukin 21 gene is associated with decreased susceptibility
to diffuse large B cell lymphoma.
AB - Interleukin 21 (IL-21) plays a key role in innate and adaptive immunity.
Polymorphisms in IL-21 gene may be greatly involved in various diseases. The aim
of the study was to investigate the association between IL-21 genetic
polymorphisms and the susceptibility to diffuse large B cell lymphoma (DLBCL). IL
21 -2498G/A and +78A/G polymorphisms were examined in 221 DLBCL patients and 243
healthy controls. We found that distributions of -2498GA genotype and -2498AA
genotype were clearly decreased in DLBCL cases compared to healthy donors (odds
ratio [OR] = 0.71, 95% confidence interval [CI] = 0.43-0.92, P = 0.021; OR =
0.36, 95 % CI = 0.15-0.48, P < 0.001; data were adjusted for age and sex).
Stratification analyses revealed that patients with advanced Ann Arbor stages
(III+IV) had further decreased percentage of -2498AA genotype than those with
primary stages (OR = 0.31, 95% CI = 0.13-0.87, P = 0.023; data were adjusted for
age and sex). In addition, we evaluated the possible effect of IL-21
polymorphisms on gene expression by examining serum level of IL-21 in patients
and controls. Data revealed that subjects carrying -2498AA genotype had
significantly higher serum level of IL-21 than those with GG genotype or GA
genotype. These data suggest that IL-21 -2498G/A polymorphism is associated with
decreased susceptibility to DLBCL and may increase serum level of IL-21.
PMID- 25117078
TI - Real-time analysis of endogenous protoporphyrin IX fluorescence from delta
aminolevulinic acid and its derivatives reveals distinct time- and dose-dependent
characteristics in vitro.
AB - Photodynamic therapy (PDT) and photodiagnosis based on the intracellular
production of the photosensitizer protoporphyrin IX (PPIX) by administration of
its metabolic precursor -aminolevulinic acid (ALA) achieved their breakthrough
upon the clinical approval of MAL (ALA methyl ester) and HAL (ALA hexyl ester).
For newly developed ALA derivatives or application in new tumor types, in vitro
determination of PPIX formation involves multiparametric experiments covering
variable pro-drug concentrations, medium composition, time points of analysis,
and cell type(s). This study uses a fluorescence microplate reader with a built
in temperature and atmosphere control to investigate the high-resolution long
term kinetics (72 h) of cellular PPIX fueled by administration of either ALA,
MAL, or HAL for each 10 different concentrations. For simultaneous proliferation
correction, A431 cells were stably transfected with green fluorescent protein.
The results indicate that the peak PPIX level is a function of both, incubation
concentration and period: maximal PPIX is generated with 1 to 2-mM ALA/MAL or
0.125-mM HAL; also, the PPIX peak shifts to longer incubation periods with
increasing pro-drug concentrations. The results underline the need for detailed
temporal analysis of PPIX formation to optimize ALA (derivative)-based PDT or
photodiagnosis and highlight the value of environment-controlled microplate
readers for automated in vitro analysis.
PMID- 25117079
TI - Aberration correction during real time in vivo imaging of bone marrow with
sensorless adaptive optics confocal microscope.
AB - We have demonstrated adaptive correction of specimen-induced aberration during in
vivo imaging of mouse bone marrow vasculature with confocal fluorescence
microscopy. Adaptive optics system was completed with wavefront sensorless
correction scheme based on stochastic parallel gradient descent algorithm. Using
image sharpness as the optimization metric, aberration correction was performed
based upon Zernike polynomial modes. The experimental results revealed the
improved signal and resolution leading to a substantially enhanced image contrast
with aberration correction. The image quality of vessels at 38- and 75-MUm depth
increased three times and two times, respectively. The corrections allowed us to
detect clearer bone marrow vasculature structures at greater contrast and improve
the signal-to-noise ratio.
PMID- 25117080
TI - Zn(2+) effect on structure and residual hydrophobicity of amyloid beta-peptide
monomers.
AB - The aggregation of amyloid beta-peptide (Abeta peptide) has been associated with
the pathogenesis of Alzheimer's disease (AD). In the present study, we aimed to
disclose how Zn(2+) affects the Abeta aggregation in detail. Thus, molecular
dynamics simulation was implemented to elucidate the changes of structure and
residual hydrophobicity upon Zn(2+) coordination. Our results show that Zn(2+)
can strongly influence the structural properties of Abeta40 and Abeta42 by
reducing helical formation and increasing turn formation to expose the
hydrophobic regions. Furthermore, hydrophobicity of Zn(2+)-Abeta40 and Zn(2+)
Abeta42 was much higher than that of each monomer, since Zn(2+) binding can
significantly influence the hydrophilic domains of Abeta. The further analyses
indicate that not only four residues (H6, E11, H13, and H14) but also R5, D7,
K16, K28, and terminal residues influence hydrophobicity upon Zn(2+)
coordination. Importantly, R5, K16, and K28 play a crucial role to regulate
solvation-free energies. This work is helpful to understand the fundamental role
of Zn(2+) in aggregation, which could be useful for further development of new
drugs to inhibit Zn(2+)-Abeta aggregation.
PMID- 25117076
TI - Toward microendoscopy-inspired cardiac optogenetics in vivo: technical overview
and perspective.
AB - The ability to perform precise, spatially localized actuation and measurements of
electrical activity in the heart is crucial in understanding cardiac
electrophysiology and devising new therapeutic solutions for control of cardiac
arrhythmias. Current cardiac imaging techniques (i.e. optical mapping) employ
voltage- or calcium-sensitive fluorescent dyes to visualize the electrical signal
propagation through cardiac syncytium in vitro or in situ with very high
spatiotemporal resolution. The extension of optogenetics into the cardiac field,
where cardiac tissue is genetically altered to express light-sensitive ion
channels allowing electrical activity to be elicited or suppressed in a precise
cell-specific way, has opened the possibility for all-optical interrogation of
cardiac electrophysiology. In vivo application of cardiac optogenetics faces
multiple challenges and necessitates suitable optical systems employing fiber
optics to actuate and sense electrical signals. In this technical perspective, we
present a compendium of clinically relevant access routes to different parts of
the cardiac electrical conduction system based on currently employed catheter
imaging systems and determine the quantitative size constraints for endoscopic
cardiac optogenetics. We discuss the relevant technical advancements in
microendoscopy, cardiac imaging, and optogenetics and outline the strategies for
combining them to create a portable, miniaturized fiber-based system for all
optical interrogation of cardiac electrophysiology in vivo.
PMID- 25117083
TI - Emergency ultrasound: Leveling the training and assessment landscape.
PMID- 25117084
TI - The impact of the Massachusetts health care reform on unpaid medical bills.
AB - The Massachusetts health care reform was expected to reduce the financial burden
of medical care, but literature exploring this effect is limited. In this study,
we use hospital financial information and a panel data difference-in-difference
model to assess the impact of the Massachusetts health care reform on unpaid
medical bills. We find that the reform reduced the financial burden for patients,
reflected by a 26percent decrease in hospital bad debt. The effect was more
pronounced among safety-net hospitals, indicating a larger benefit for the most
vulnerable population.
PMID- 25117085
TI - Financial burden of medical out-of-pocket spending by state and the implications
of the 2014 Medicaid expansions.
AB - This study is the first to offer a detailed look at the burden of medical out-of
pocket spending, defined as total family medical out-of-pocket spending as a
proportion of income, for each state. It further investigates which states have
greater shares of individuals with high burden levels and no Medicaid coverage
but would be Medicaid eligible under the 2014 rules of the Affordable Care Act
should their state choose to participate in the expansion. This work suggests
which states have the largest populations likely to benefit, in terms of lowering
medical spending burden, from participating in the 2014 adult Medicaid
expansions.
PMID- 25117081
TI - Heart failure care in low- and middle-income countries: a systematic review and
meta-analysis.
AB - BACKGROUND: Heart failure places a significant burden on patients and health
systems in high-income countries. However, information about its burden in low-
and middle-income countries (LMICs) is scant. We thus set out to review both
published and unpublished information on the presentation, causes, management,
and outcomes of heart failure in LMICs. METHODS AND FINDINGS: Medline, Embase,
Global Health Database, and World Health Organization regional databases were
searched for studies from LMICs published between 1 January 1995 and 30 March
2014. Additional unpublished data were requested from investigators and
international heart failure experts. We identified 42 studies that provided
relevant information on acute hospital care (25 LMICs; 232,550 patients) and 11
studies on the management of chronic heart failure in primary care or outpatient
settings (14 LMICs; 5,358 patients). The mean age of patients studied ranged from
42 y in Cameroon and Ghana to 75 y in Argentina, and mean age in studies largely
correlated with the human development index of the country in which they were
conducted (r = 0.71, p<0.001). Overall, ischaemic heart disease was the main
reported cause of heart failure in all regions except Africa and the Americas,
where hypertension was predominant. Taking both those managed acutely in hospital
and those in non-acute outpatient or community settings together, 57% (95%
confidence interval [CI]: 49%-64%) of patients were treated with angiotensin
converting enzyme inhibitors, 34% (95% CI: 28%-41%) with beta-blockers, and 32%
(95% CI: 25%-39%) with mineralocorticoid receptor antagonists. Mean inpatient
stay was 10 d, ranging from 3 d in India to 23 d in China. Acute heart failure
accounted for 2.2% (range: 0.3%-7.7%) of total hospital admissions, and mean in
hospital mortality was 8% (95% CI: 6%-10%). There was substantial variation
between studies (p<0.001 across all variables), and most data were from urban
tertiary referral centres. Only one population-based study assessing incidence
and/or prevalence of heart failure was identified. CONCLUSIONS: The presentation,
underlying causes, management, and outcomes of heart failure vary substantially
across LMICs. On average, the use of evidence-based medications tends to be
suboptimal. Better strategies for heart failure surveillance and management in
LMICs are needed. Please see later in the article for the Editors' Summary.
PMID- 25117082
TI - Identification of cancer stem cells and a strategy for their elimination.
AB - It has been established previously that up to 40% of mouse CD34(+) hematopoietic
stem cells are capable of internalizing exogenous dsDNA fragments both in vivo
and ex vivo. Importantly, when mice are treated with a combination of
cyclophosphamide and dsDNA, the repair of interstrand crosslinks in hematopoietic
progenitors is attenuated, and their pluripotency is altered. Here we show for
the first time that among various actively proliferating mammalian cell
populations there are subpopulations capable of internalizing dsDNA fragments. In
the context of cancer, such dsDNA-internalizing cell subpopulations display
cancer stem cell-like phenotype. Furthermore, using Krebs-2 ascites cells as a
model, we found that upon combined treatment with cyclophosphamide and dsDNA,
engrafted material loses its tumor-initiating properties which we attribute to
the elimination of tumor-initiating stem cell subpopulation or loss of its
tumorigenic potential.
PMID- 25117086
TI - Demand for temporary agency nurses and nursing shortages.
AB - There is an ongoing debate about the reasons for the growth of temporary
employment of registered nurses (RNs). Some argue that efficiency incentives to
increase flexibility and reduce labor costs are the principal cause, while others
point to shortages of RNs as the stronger determinant. Using hospital-level data
from California's Office of Statewide Health Planning and Development, we find a
significant trend of increasing demand for agency nurses during the years of RN
shortage. Demand rose with inpatient days, patient demand fluctuation, and the
level of fringe benefits. Competition between hospitals and unionization,
however, did not affect hospitals' demand for temporary RNs.
PMID- 25117087
TI - Impact of CPOE usage on medication management process costs and quality outcomes.
AB - We assess the impact of computerized physician order entry (CPOE) systems usage
on cost and process quality in the medication management process. Data are
compiled from 1,014 U.S. acute-care hospitals that have already implemented CPOE.
Data sources include the American Hospital Association, HIMSS Analytics, and the
Centers for Medicare and Medicaid Services. We examine the association of CPOE
usage with nursing and pharmacy salary costs, and evidence-based medication
process compliance. Empirical findings controlling for endogeneity in usage show
that benefits accrue even when 100 percent usage is not achieved. We demonstrate
that the relationship of CPOE usage with cost and compliance is non-linear.
PMID- 25117088
TI - Polymorphisms in the DNA repair gene ERCC2/XPD and breast cancer risk: a HapMap
based case-control study among Han Women in a Chinese less-developed area.
AB - AIMS: Genetic variations in DNA repair genes may impact repair functions, DNA
damage, and breast cancer risk. This study is aimed to assess the associations of
genetic polymorphisms in excision repair cross-complementing group 2 (ERCC2) with
the risk of developing breast cancer. MATERIALS AND METHODS: In total, 101
histopathologically confirmed breast cancer cases and 101 age/region-matched
healthy controls were genotyped for rs 3916840, rs 1799793, and rs 238416 in
ERCC2 by polymerase chain reaction-restriction fragment length polymorphism.
RESULTS: The rs 238416 heterozygous GA genotype combined with the rs 238416
genotypes (GA+AA) showed a significant association with breast cancer
susceptibility (corrected p<0.01, odds ratio [OR]=0.29, 95% confidence interval
[CI]=0.15-0.54; corrected p<0.01, OR=0.31, 95% CI=0.17-0.56, respectively). The
rs 238416 GA genotype carriers had a decreased risk of breast cancer. However, we
observed no significant association between the rs 3916840 and rs 1799793
polymorphisms in ERCC2 and breast cancer risk. Moreover, haplotype analysis
showed that the ACG haplotype was associated with a significantly decreased risk
of breast cancer, whereas the GCG haplotype was associated with a significantly
increased risk of breast cancer (corrected p=0.004 and p=0.002, respectively).
Multifactor dimensionality reduction analysis demonstrated that the interactions
between rs 3916840 and rs 238416 were significantly synergistic. CONCLUSION: To
the best of our knowledge, this study is the first to demonstrate that the rs
238416 heterozygous genotype likely has a higher DNA repair capacity and, thus,
can be protective against breast cancer in Chinese Han women.
PMID- 25117089
TI - Interactions between voluntary and involuntary attention modulate the quality and
temporal dynamics of visual processing.
AB - Successfully navigating a dynamic environment requires the efficient distribution
of finite neural resources. Voluntary (endogenous) covert spatial attention
selectively allocates those processing resources to goal-relevant locations in
the visual scene in the absence of eye movements. However, the allocation of
spatial attention is not always voluntary; abrupt onsets in the visual periphery
automatically enhance processing of nearby stimuli (exogenous attention). In
dynamic environments, exogenous events and internal goals likely compete to
determine the distribution of attention, but how such competition is resolved is
not well understood. To investigate how exogenous events interact with the
concurrent allocation of voluntary attention, we used a speed-accuracy trade-off
(SAT) procedure. SAT conjointly measures the rate of information accrual and
asymptotic discriminability, allowing us to measure how attentional interactions
unfold over time during stimulus processing. We found that both types of
attention sped information accrual and improved discriminability. However,
focusing endogenous attention at the target location reduced the effects of
exogenous cues on the rate of information accrual and rendered negligible their
effects on asymptotic discriminability. We verified the robustness of these
findings in four additional experiments that targeted specific, critical response
delays. In conclusion, the speed and quality of visual processing depend
conjointly on internally and externally driven attentional states, but it is
possible to voluntarily diminish distraction by irrelevant events in the
periphery.
PMID- 25117090
TI - The role of mnemonic processes in pure-target and pure-foil recognition memory.
AB - Surprisingly, response patterns in a recognition memory test are very similar
regardless of whether the test list contains both targets and foils or just one
class of items. To better understand these effects, we evaluate performance over
the course of testing. Output interference (OI) is the decrease in performance
across test trials due to an increase in noise caused by encoded test items.
Critically, OI is predicted on pure lists if the mnemonic evidence for each test
item is evaluated. In two experiments, participants received accurate feedback,
no feedback, or random feedback that was unrelated to the response on each test
trial and pure or standard test lists. When no feedback was provided, performance
was nearly identical for standard and pure test lists, replicating previous
findings. Only in the presence of accurate feedback were participants able to
successfully adapt to pure list environments and improve their accuracy.
Critically, OI was observed, demonstrating that participants continued to
evaluate mnemonic evidence even in pure list conditions. We discuss the
implication of these data for models of memory.
PMID- 25117091
TI - The perception of Glass patterns by starlings (Sturnus vulgaris).
AB - Glass patterns are structured dot stimuli used to investigate the visual
perception of global form. Studies have demonstrated that humans and pigeons
differ in their processing of circular versus linearly organized Glass patterns.
To test whether this comparative difference is characteristic of birds as a
phylogenetic class, we investigated for the first time how a passerine
(starlings, Sturnus vulgaris) discriminated multiple Glass patterns from random
dot stimuli in a simultaneous discrimination. By examining acquisition, steady
state performance, and the effects of diminishing global coherence, it was found
that the perception of Glass patterns by 5 starlings differed from human
perception and corresponded to that established with pigeons. This suggests an
important difference in how birds and primates are specialized in their
processing of circular visual patterns, perhaps related to face perception, or in
how these highly visual animals direct attention to the global and local
components of spatially separated form stimuli.
PMID- 25117092
TI - Analytical and clinical performance of a new point of care LABGEOIB D-dimer test
for diagnosis of venous thromboembolism.
AB - LABGEO(IB) D-dimer Test is a newly developed POC D-dimer assay and the first
commercially available POC immunoassay instrument that exploits the disk rotation
method for extraction of plasma. Citrate plasma was obtained from 201 apparently
healthy subjects and 91 patients suspected for VTE, and their D-dimer level was
measured by the LABGEO(IB) D-Dimer Test (LABGEO D-dimer) and HemosIL D-dimer test
as a comparative method. To examine the effect of blood cells and anticoagulant,
paired blood samples anticoagulated by heparin and citrate were obtained from
various postoperative patients. The overall diagnostic performance of LABGEO(IB)
D-dimer and HemosIL was comparable with similar area under ROC curve (p=0.79).
The cut-off levels recommended by manufacturers (LABGEO D-dimer: 0.45 MUg/ml
fibrinogen equivalent unit (FEU), HemosIL: 0.23 MUg/ml D-dimer unit (DDU)) and
those yielding highest diagnostic efficiency (LABGEO D-dimer: 1.41 MUg/ml FEU;
HemosIL: 0.85 MUg/ml DDU), were chosen for the evaluation. For LABGEO D-dimer
negative predictive value (NPV), positive predictive value (PPV), sensitivity,
specificity, and negative likelihood ratio (LR-neg) were 93-100%, 67-89%, 93
100%, 53-89% and 0.00-0.08. For HemosIL D-dimer, NPV, PPV, sensitivity,
specificity and LR-neg were 90 - 100%, 76-95%, 89-100%, 70-96% and 0.00-0.12, all
comparable to results for LABGEO D-dimer. LABGEO D-dimer test demonstrated
acceptable performance when used for the VTE diagnostic work-up.
PMID- 25117094
TI - Accumulation and absorption of serum amyloid A and apolipoprotein E fragments in
the course of AA amyloidosis: a study in a mouse model.
AB - Reactive AA amyloidosis develops secondary to chronic inflammatory disorders.
Serum amyloid A protein (SAA) and its degradation products, named AAs, are the
main components of amyloid deposits, while apolipoprotein E (apoE) fragments are
the minor components. To further understand the molecular mechanism of AA
amyloidosis, we examined SAA/AAs moieties and apoE in the spleen and plasma
throughout the amyloid-generating and amyloid-absorbing phases in a mouse model.
SAA and four AA species (8.5kDa, 7.8kDa, 7.0kDa, and 6.2kDa) were detected in the
spleen. SAA and the 8.5 kDa and 7.8 kDa AAs were prominent in the acute phase,
whereas the 7.0kDa AA, the second smallest AA corresponding to the most common
form in the human disease, was prominent in the chronic phase. These results
indicate that the higher molecular weight species first constituted the fibril,
followed by the 7.0kDa species, which were finally absorbed. ApoE was a component
of the amyloid deposits at a degradation size from the beginning and was absorbed
without being converted to another size. Degradation products, either from SAA or
apoE, did not appear in the plasma during the course of the disease. A more
detailed understanding of the moieties of amyloid-related peptides may help in
the development of a method that can indicate the disease activity of AA
amyloidosis.
PMID- 25117093
TI - The anti-cancer peptide, PNC-27, induces tumor cell necrosis of a poorly
differentiated non-solid tissue human leukemia cell line that depends on
expression of HDM-2 in the plasma membrane of these cells.
AB - GOALS: We have developed the anti-cancer peptide, PNC-27, which is a membrane
active peptide that binds to the HDM-2 protein expressed in the cancer cell
membranes of solid tissue tumor cells and induces transmembrane pore formation in
cancer, but not in normal cells, resulting in tumor cell necrosis that is
independent of p53 activity in these cells. We now extend our study to non-solid
tissue tumor cells, in this case, a primitive, possible stem cell human leukemia
cell line (K562) that is also p53-homozygously deleted. Our purpose was twofold:
to investigate if these cells likewise express HDM-2 in their plasma membranes
and to determine if our anti-cancer peptide induces tumor cell necrosis in these
non-solid tissue tumor cells in a manner that depends on the interaction between
the peptide and membrane-bound HDM-2. PROCEDURES: The anti-cancer activity and
mechanism of PNC-27, which carries a p53 aa12-26-leader sequence connected on its
carboxyl terminal end to a trans-membrane-penetrating sequence or membrane
residency peptide (MRP), was studied against p53-null K562 leukemia cells. Murine
leukocytes were used as a non-cancer cell control. Necrosis was determined by
measuring the lactate dehydrogenase (LDH) release and apoptosis was determined by
the detection of Caspases 3 and 7. Membrane colocalization of PNC-27 with HDM-2
was analyzed microscopically using fluorescently labeled antibodies against HDM-2
and PNC-27 peptides. RESULTS: We found that K562 cells strongly express HDM-2
protein in their membranes and that PNC-27 co-localizes with this protein in the
membranes of these cells. PNC-27, but not the negative control peptide PNC-29, is
selectively cytotoxic to K562 cells, inducing nearly 100 percent cell killing
with LDH release. In contrast, this peptide had no effect on the lymphocyte
control cells. CONCLUSIONS: The results suggest that HDM-2 is expressed in the
membranes of non-solid tissue tumor cells in addition to the membranes of solid
tissue tumor cells. Since K-562 cells appear to be in the stem cell family, the
results suggest that early developing tumor cells also express HDM-2 protein in
their membranes. Since PNC-27 induces necrosis of K-562 leukemia cells and co
localizes with HDM-2 in the tumor cell membrane as an early event, we conclude
that the association of PNC-27 with HDM-2 in the cancer cell membrane results in
trans-membrane pore formation which results in cancer cell death, as previously
discovered in a number of different solid tissue tumor cells. Since K562 cells
lack p53 expression, these effects of PNC-27 on this leukemia cell line occur by
a p53-independent pathway.
PMID- 25117095
TI - Calcium oxalate crystallization index (COCI): an alternative method for
distinguishing nephrolithiasis patients from healthy individuals.
AB - Urinary supersaturation triggers lithogenic crystal formation. We developed an
alternative test, designated calcium oxalate crystallization index (COCI), to
distinguish nephrolithiasis patients from healthy individuals based on their
urinary crystallization capability. The effect of urine volume, oxalate,
phosphate, citrate, potassium, and sodium on COCI values was investigated. COCI
values were determined in 24-hr urine obtained from nephrolithiasis patients
(n=72) and matched healthy controls (n=71). Increases in urine oxalate and
phosphate and decreases in urine volume and citrate resulted in significantly
increased COCI values. The urinary COCI in nephrolithiasis patients was
significantly higher than that in healthy individuals. Two healthy subjects who
had elevated COCI values were found to have asymptomatic kidney calculi. The
receiver operating characteristic analysis showed an area under the curve of the
urinary COCI test of 0.9499 (95%CI: 0.9131-0.9868) for distinguishing between
nephrolithiasis and healthy subjects. At the cutoff of 165 mg oxalate
equivalence/day, the urinary COCI test provided sensitivity, specificity, and
accuracy amounts of 83.33%, 97.18%, and 90.21%, respectively. Urinary COCI values
were primarily dependent on urine volume, oxalate, and phosphate. The test
provided high sensitivity and specificity for clinically discriminating
nephrolithiasis patients from healthy controls. It might be used to detect
individuals with asymptomatic kidney calculi.
PMID- 25117096
TI - Extracellular MCT4 is a possible indicator for skeletal muscle MHC fiber type
change.
AB - Biochemical markers that indicate fiber type rearrangement in myosin heavy chain
(MHC) have been used to evaluate the effectiveness of exercise and/or
rehabilitation therapy. The aim of this study was to investigate whether measures
of extracellular monocarboxylate transporter 4 (MCT4) protein can help in the
detection of MHC fiber type variation. Human skeletal muscle cells (HSkMCs) were
succumbed to high atmospheric pressure. Immunoblot analyses were performed to
evaluate MHC fiber type change, and an enzyme-linked immunosorbent assay system
was developed for the quantification of MCT4 concentration. Static pressurization
to HSkMCs resulted in an increase in cells of median diameter (18 MUm). The
proportion of MHC Type I fiber was increased by pressurization, and MCT4 protein
concentration in the culture medium was also increased in the pressurized sample.
We conclude that the amount of MCT4 in culture medium released from HSkMCs
reflects fiber type changes in MHC.
PMID- 25117097
TI - Associations of single nucleotide polymorphisms related to insulin resistance
with polycystic ovary syndrome.
AB - BACKGROUND: We investigated and validated most of the hitherto-suggested
polymorphisms for PCOS. MATERIALS AND METHODS: DNA samples from 359 pre
menopausal Korean women with PCOS (n=196) and without (n=166) were analyzed by
primer extension and matrix-assisted laser desorption/ionization time-of-flight
(MALDI-TOF) mass spectrometry using iPLEX Gold technology from Sequenom (Sequenom
Inc, San Diego, CA, USA) to determine the genotypic frequency of 80 single
nucleotide polymorphisms (SNPs) from the 49 genes. RESULTS: Four SNPs
(rs10060745, rs1719889, rs680, rs705379) showed moderate association with a risk
of PCOS. Three (rs1719889, rs680, and rs705379) out of four SNPs were related to
insulin resistance. The rs705379 showed significant association with increased
fasting glucose (p=0.045) and serum 2-h C-peptide level (p=0.026). The rs1719889
showed significant association with fasting glucose level (p=0.03). CONCLUSION:
Our results provide evidence for the relationship between high prevalence of
insulin resistance and PCOS.
PMID- 25117098
TI - Life style intervention in moderately overweight individuals is associated with
decreased levels of cathepsins L and S in plasma.
AB - BACKGROUND: Adipose tissue cells produce cathepsins L and S, which have
proatherogenic effects. Obesity is strongly linked to atherogenesis,
cardiovascular morbidity, and mortality. OBJECTIVE: The aim of the present study
was to see if life style interventions/weight reduction could decrease cathepsin
L and S levels in blood plasma. METHOD: Study subjects (n=31) were recruited to a
life style intervention program aiming at increased physical activity, more
healthy eating habits, and weight reduction for most of the participants. Blood
samples were collected at inclusion and after 4 and 8 weeks. RESULTS: Cathepsin L
was significantly reduced at 4 weeks (p<0.0001) and 8 weeks (p=0.0004). A similar
reduction was also seen for cathepsin S at 4 weeks (p=0.03) and 8 weeks
(p=0.008). No significant change in fractalkine values was observed at 4 weeks
(p=0.58), but a significant increase was apparent at 8 weeks (p=0.0002).
CONCLUSION: The intervention program resulted in significant reductions of
cathepsin L and S levels in plasma after 4 and 8 weeks of intervention.
PMID- 25117099
TI - Correlation between low folate levels and hyperhomocysteinemia, but not with
vitamin B12 in hypertensive patients.
AB - INTRODUCTION: Hypertension is considered to be among the most important risk
factors for cardiovascular and cerebrovascular diseases. In recent years, several
investigators have reported that high plasma levels of total homocysteine (t-hcy)
has a key role in the development of hypertension, and the deficiency of B
complex vitamins could increase the risk of hypertension. The purpose of this
study was to investigate the relationship between plasma homocysteine, folate and
vitamin B12 in hypertensive patients. MATERIALS AND METHODS: In 116 patients with
hypertension and 81 healthy subjects, total plasma homocysteine, vitamin B12 and
folate levels were measured. RESULTS AND DISCUSSION: Homocysteine was
significantly higher in patients than in control subjects (22.9+/-3.5 versus
9.0+/-2.3 MUmol/L respectively, p<0.001); the folate plasma concentrations in
hypertensive patients were significantly lower than in control subjects (6.7+/
5.0 ng/ml and 9.0+/-4.4 ng/ml respectively, p<0.05). Moreover, no differences in
vitamin B12 plasma levels were observed when comparing the levels of hypertensive
patients and those of the controls (440+/-223 pg/ml vs 491+/-185 pg/ml
respectively, p>0.05). Our results confirmed that, as previously observed,
elevated t-hcy levels and low folate levels, but not vitamin B12 levels, are
significantly associated with hypertension.
PMID- 25117100
TI - Higher sensitivity of capillary electrophoresis in detecting hemoglobin
A2'compared to traditional gel electrophoresis.
AB - HbA2' (also called Hb B2) is the most common delta-globin chain defect and is
reported to occur in 1-2% of the African American population. The major clinical
significance of HbA2' is that the failure to detect it might lead to an
underestimation of the total HbA2, leading to failure to diagnose beta
thalassemia minor. In order to diagnose beta-thalassemia minor, both HbA2 and
HbA2' levels must be combined.Hb A2' accounts for a small percentage (1-2%) of
the total hemoglobin in heterozygotes. It is difficult to detect this small
amount by traditional gel electrophoresis. Using HPLC Hb A2' is easily detected
as it produces a minor peak in the S window. Other conditions which might
interfere with detection of HbA2' by HPLC include Hb S trait or Hb SS disease (Hb
A2' hidden in the S peak), transfused Hb SS (Hb S peak may be very small), Hb C
trait or Hb CC disease (glycosylated Hb C elutes in the S window), and Hb G (Hb
G2 elutes in the S window). All of the above conditions, including Hb A2', occur
most commonly in the same ethnic group (African American). We reviewed 654
consecutive cases over a period of three months for the presence of Hb A2' in our
laboratory where capillary electrophoresis is used as the primary diagnostic
tool. We detected seven cases (1.07 %) of HbA2'. In contrast, we did not detect
any HbA2' using conventional gel electrophoresis in the last one year (2,580
cases). Although in none of the seven cases the sum of Hb A2 and Hb A2' exceeded
3.5%, we believe that capillary electrophoresis allows for a better detection of
Hb A2' than gel electrophoresis and HPLC.
PMID- 25117101
TI - ABCB1 expression in peptic ulcer patients and its connection with H. pylori
Infection.
AB - Glycoprotein P, encoded by the ABCB1 gene, plays an important role in gastric
mucosa homeostasis and can influence the eradication therapy outcome in H. pylori
infected individuals. In the study we examined the ABCB1 expression level in 128
peptic ulcer patients by real-time PCR. There was no correlation between gene
expression and the presence of H. pylori or the H. pylori infection intensity.
The expression level did not differ between women and men. However, the levels
were higher in patients who were over 54 years old than those who were aged up to
54 years old. As ABCB1 expression is largely determined by genetic polymorphisms,
in the future, expression data will be related to the patients' ABCB1 genotypes.
PMID- 25117102
TI - Role of apolipoprotein AI gene polymorphism (G-75A and C+83T) in essential
hypertension in Indian population.
AB - Hypertension is becoming a public health emergency worldwide. It has been seen
that both genetics and gene-environment interactions are major determinants of
lipoprotein abnormalities and hypertension. This study elucidates the effect of
apolipoprotein AI gene polymorphism (G-75A and C+83T) in 50 cases of essential
hypertension and equal number of age & sex matched control subjects in the Indian
population. Higher instances of obesity and more adverse biochemical profiles
were found in hypertensives [GA (74%) and CT (56%) most commonly observed
genotypes]. Presence of A and T alleles and GA (-75 bp) and CT (+83 bp)
heterozygosity in apolipoprotein AI gene play an important role in essential
hypertension (GA genotype had an odds ratio of 4.27 (1.69-10.96) of developing
essential hypertension). The odds ratio for the GA genotype was 3.74 (95%CI, 0.83
9.0) in the presence of confounding factors including total proteins, albumin,
amylase, cholesterol, triglycerides, LDL, VLDL and body mass index. It indicates
one of the potential areas where population studies may be taken up for
identifying the genetic basis of essential hypertension.
PMID- 25117103
TI - Influence of iron regulating genes mutations on iron status in Egyptian patients
with sickle cell disease.
AB - Mutations of the HAMP gene and HFE gene have a role in iron overload. We assessed
the frequency of the G71D mutation of the HAMP gene and the H63D mutation of the
HFE gene and the correlation between these mutations as well as the correlation
between them and the iron overload in sickle cell disease (SCD) patients.
Genotyping of G71D of HAMP and of H63D of HFE variants was performed by
polymerase chain reaction-restriction fragment length polymorphism on 47 SCD
patients and 45 controls. The iron status was assessed by serum ferritin and
transferrin saturation. We found 61.7% of the patients had a wild genotype in
both genes, 14.9% had a variation in HAMP-G71D, 27.7% had a variation in HFE
H63D, and 4.3% had variations in both. Patients with either HAMP-G71D or HFE-H63D
variants did not show significant difference in iron status in comparison to
patients with wild type genotypes. Multivariate regression analysis revealed that
the number of mutations harbored by the patients tends to affect the serum
ferritin level; p=0.07. Thus, The HAMP-G71D and HFE-H63D variants are not
uncommon among the Egyptian SCD patients; neither of them alone was found to be a
major determinant of iron overload in the studied patients. Nevertheless, the
number of harboured mutations may increase the probability of iron overload in
these patients.
PMID- 25117104
TI - A cooperative approach to diagnosis of rare diseases: primitive myxoid
mesenchymal tumor of infancy.
AB - Primitive Myxoid Mesenchymal Tumor of Infancy (PMMTI) is a recently recognized
locally aggressive myofibroblastic tumor. It is a low- to intermediate-grade
fibroblastic malignancy with a high local recurrence rate but low metastatic
potential and is composed of primitive spindled cells in a myxoid background. We
present the eleventh reported case of PMMTI, occurring in the sinonasal tract of
a 3-year old child. This case is novel in both the relatively older age of the
child, the location of the tumor, and the role that immunohistochemical stains,
and cytogenetic analysis played in differentiating it from similar diagnoses that
differ considerably in their chemosensitivity and recurrence rates. Close
collaboration between the pathologist and surgeon was crucial as different
diagnoses would have led to vastly different treatment strategies for the
patient.
PMID- 25117106
TI - Traumatic neuroma of the anus after Milligan-Morgan hemorrhoidectomy.
AB - There are several clinical settings of traumatic neuroma and a few may occur
following surgical procedures. A 42-year-old man presented with anal pain five
years after a Milligan Morgan hemorrhoidectomy for prolapsing hemorrhoids. A
4*4*3 mm sized anal polyp was seen during a rectal examination at a follow-up
five years after surgery. The patient complained of point tenderness, pruritus,
and anal discomfort as well as fecal retention. An endoscopy revealed a rectal
polyp. Remarkably, histopathological examination and immunohistochemistry of the
excised polyp showed a polypoid traumatic neuroma of the rectal plexus. After the
excision of the polyp, the patient's complaint resolved completely. Traumatic
neuromas may be a cause of significant pain and tenderness in patients with anal
surgery or repair of anal lacerations. Interestingly, this is the second case of
anal traumatic neuroma since Dr. Marks' first case in 1956 and is a possible
complication of Milligan Morgan hemorrhoidectomy for prolapsing hemorrhoids.
Similar complications of rectal surgery are reviewed.
PMID- 25117105
TI - Two novel FAH gene mutations in a patient with hereditary tyrosinemia type I.
AB - BACKGROUND: Hereditary tyrosinemia type I (HT I) is a severe inborn metabolic
disorder affecting the tyrosine degradation pathway. Most untreated patients die
within the first two years of life. HT I results from fumarylacetoacetate
hydrolase (FAH) deficiency caused by mutations in the FAH gene. The diagnosis of
HT I is confirmed by measuring FAH enzyme activity in cultured fibroblasts or
liver tissue and/or detecting disease-causing mutations in the FAH gene. METHODS:
A female neonate was referred to our hospital for further evaluation of an
abnormal newborn screening test that showed elevated tyrosine levels. We analyzed
amino acids and organic acids in the patient's blood and urine. To identify the
genetic abnormality, all the coding exons and flanking introns of the FAH gene
were analyzed via PCR. RESULTS: A repeat newborn screening test and plasma amino
acid analysis revealed increased tyrosine levels in the patient. Urine organic
acid analysis showed increased urinary excretion of 4-hydroxyphenyllactate, 4
hydroxyphenylpyruvate, and succinylacetone. Sequence analysis of the FAH gene
identified two novel variations (c.536A>G (p.Gln179Arg) and c.913+5G>A) that had
not been previously reported and that were not found in 170 healthy controls.
CONCLUSIONS: HT I was confirmed in this patient by molecular genetic analysis of
the FAH gene, with highly suggestive biochemical findings. The novel sequence
variations detected in the present study should be considered disease-causing
mutations by in silico analysis. In the Korean population, this is the first
described case of HT I caused by a point mutation in the FAH gene.
PMID- 25117107
TI - Hypercalcemia and renal failure in a young man: lessons in diagnosis.
AB - Hypercalcemia is a common clinical problem. Morbidity and mortality associated
with hypercalcemia are directly related to its underlying cause, making
identification of the correct underlying etiology vital. When hypercalcemia is
combined with acute kidney injury it points towards very specific diagnoses. We
present a case of a young man with hypercalcemia and acute kidney injury who had
multiple unusual laboratory findings that lead to the establishment of a correct
diagnosis.
PMID- 25117108
TI - Fresh frozen plasma as a source of cholesterol for newborn with Smith-Lemli-Opitz
syndrome associated with defective cholesterol synthesis.
AB - The Smith-Lemli-Opitz Syndrome (SLOS) is an autosomal recessive condition that is
characterized by a mutation in the DHCR7 encoding the 7-dehydrocholesterol-Delta7
reductase, the enzyme that catalyzes the last step in cholesterol biosynthesis.
The syndrome occurs in 1:20,000 newborns with an estimated gene carrier frequency
in US Caucasian population of 1 to 2%. The severe form of SLOS in newborns leads
to multiple malformations and mental retardation. The malformations present were
facial dysmorphisms, cleft palate, congenital heart disease, genitourinary
abnormalities, and syndactyly of the toes. The identification of the biochemical
basis of SLOS has led to the development of therapeutic regimes based on dietary
cholesterol supplementation. In this case report, we present a case of SLOS that
was treated by fresh frozen plasma to increase the level of serum Cholesterol
since oral and rectal cholesterol replacement was not possible in this instance.
PMID- 25117109
TI - "20209C-T" a variant mutation of prothrombin gene mutation in a patient with
recurrent pregnancy loss.
AB - Recurrent pregnancy loss is considered when a female undergoes at least two
consecutive, spontaneous abortions or more than two alternatively. This condition
affects approximately 5% of women in reproductive age. Several causes of
recurrent abortion have been established, but nevertheless, approximately half of
all cases remain unexplained. Thrombophilic disorders have been suggested as a
possible cause of recurrent miscarriage. A single 20210 G-A mutation of the 3'
untranslated region of (F2) has been reported as a cause of inherited
thrombophilia. The F2 G-A mutation affects 1% to 4% of the US population, and its
prevalence is higher among Caucasian women of Southern European descendants.
Studies of G20210A polymorphism have also shown conflicting associations with
recurrent abortions. In addition to G20210A polymorphism, other mutations
affecting the F2 gene have been associated with thrombosis and/or pregnancy
complications.
PMID- 25117111
TI - Shock Wave Induced Collapse of Arrays of Nanobubbles Located Next to a Lipid
Membrane: Coarse-Grained Computer Simulations.
AB - We used molecular dynamics simulations to study creation of pores in lipid
bilayer membranes by inducing shock waves in systems containing arrays of
nanobubbles next to these membranes. Shock waves impinged on the bubbles
imploding them and produced nanojets that subsequently hit the bilayers making
pores in them. Our simulations were performed using the MARTINI coarse-grained
force field. The emphasis in our study was on the interaction of shock waves with
two-bubble arrays when the bubbles were placed in different alignments. We
observed that the largest damage to the bilayer was produced when two bubbles
were positioned in a serial alignment and the bubbles touched each other. When
two touching each other bubbles were located parallel to the membrane surface and
at the same distance from the surface, the membrane damage was reduced, compared
to the damage done by explosion of two independent nanobubbles. When two
nanobubbles were placed in slanted configurations, the damage was intermediate
between damages produced by two bubbles in parallel or serial alignment. Damage
to the membrane produced by arrays containing more than two bubbles can be
understood as a combination of damage produced by all three alignments of two
bubbles.
PMID- 25117114
TI - The aqueduct: William Sartain.
PMID- 25117110
TI - Vitamin K deficiency bleeding leading to the diagnosis of Crohn's disease.
AB - We report the case of a 45 year old man who came to Emergency Room of Polyclinic
for sudden onset of localized ecchymosis and widespread hematomas. He was
subjected to blood count and first level investigations to assess coagulation.
Based on the results, second level investigations were performed. Endoscopy of
the gastrointestinal tract with histological examination revealed a diagnosis of
Crohn's disease. Vitamin K deficiency causes the formation of vitamin K-dependent
clotting factors that cannot perform their pro-coagulant action. Consequently,
patients present with hemorrhagic manifestations. Clinical and laboratory
features observed in this patient show that the deficiency of vitamin K-dependent
coagulation factors may reveal a complex clinical condition such as an
inflammatory bowel disease.
PMID- 25117115
TI - NIH's Undiagnosed Diseases Program expands: 6 new sites offer potential answers
to more patients.
PMID- 25117116
TI - Use of morcellation to remove fibroids scrutinized at FDA hearings.
PMID- 25117126
TI - A piece of my mind. If these walls could talk.
PMID- 25117127
TI - Flexible sigmoidoscopy for colorectal cancer screening: more evidence, persistent
ironies.
PMID- 25117128
TI - Meta-analysis as evidence: building a better pyramid.
PMID- 25117129
TI - Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and
mortality: a randomized clinical trial.
AB - IMPORTANCE: Colorectal cancer is a major health burden. Screening is recommended
in many countries. OBJECTIVE: To estimate the effectiveness of flexible
sigmoidoscopy screening on colorectal cancer incidence and mortality in a
population-based trial. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical
trial of 100,210 individuals aged 50 to 64 years, identified from the population
of Oslo city and Telemark County, Norway. Screening was performed in 1999-2000
(55-64-year age group) and in 2001 (50-54-year age group), with follow-up ending
December 31, 2011. Of those selected, 1415 were excluded due to prior colorectal
cancer, emigration, or death, and 3 could not be traced in the population
registry. INTERVENTIONS: Participants randomized to the screening group were
invited to undergo screening. Within the screening group, participants were
randomized 1:1 to receive once-only flexible sigmoidoscopy or combination of once
only flexible sigmoidoscopy and fecal occult blood testing (FOBT). Participants
with positive screening test results (cancer, adenoma, polyp >=10 mm, or positive
FOBT) were offered colonoscopy. The control group received no intervention. MAIN
OUTCOMES AND MEASURES: Colorectal cancer incidence and mortality. RESULTS: A
total of 98,792 participants were included in the intention-to-screen analyses,
of whom 78,220 comprised the control group and 20,572 comprised the screening
group (10,283 randomized to receive a flexible sigmoidoscopy and 10,289 to
receive flexible sigmoidoscopy and FOBT). Adherence with screening was 63%. After
a median of 10.9 years, 71 participants died of colorectal cancer in the
screening group vs 330 in the control group (31.4 vs 43.1 deaths per 100,000
person-years; absolute rate difference, 11.7 [95% CI, 3.0-20.4]; hazard ratio
[HR], 0.73 [95% CI, 0.56-0.94]). Colorectal cancer was diagnosed in 253
participants in the screening group vs 1086 in the control group (112.6 vs 141.0
cases per 100,000 person-years; absolute rate difference, 28.4 [95% CI, 12.1
44.7]; HR, 0.80 [95% CI, 0.70-0.92]). Colorectal cancer incidence was reduced in
both the 50- to 54-year age group (HR, 0.68; 95% CI, 0.49-0.94) and the 55- to 64
year age group (HR, 0.83; 95% CI, 0.71-0.96). There was no difference between the
flexible sigmoidoscopy only vs the flexible sigmoidoscopy and FOBT screening
groups. CONCLUSIONS AND RELEVANCE: In Norway, once-only flexible sigmoidoscopy
screening or flexible sigmoidoscopy and FOBT reduced colorectal cancer incidence
and mortality on a population level compared with no screening. Screening was
effective both in the 50- to 54-year and the 55- to 64-year age groups. TRIAL
REGISTRATION: clinicaltrials.gov Identifier: NCT00119912.
PMID- 25117130
TI - Perioperative atrial fibrillation and the long-term risk of ischemic stroke.
AB - IMPORTANCE: Clinically apparent atrial fibrillation increases the risk of
ischemic stroke. In contrast, perioperative atrial fibrillation may be viewed as
a transient response to physiological stress, and the long-term risk of stroke
after perioperative atrial fibrillation is unclear. OBJECTIVE: To examine the
association between perioperative atrial fibrillation and the long-term risk of
stroke. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using
administrative claims data on patients hospitalized for surgery (as defined by
surgical diagnosis related group codes), and discharged alive and free of
documented cerebrovascular disease or preexisting atrial fibrillation from
nonfederal California acute care hospitals between 2007 and 2011. Patients
undergoing cardiac vs other types of surgery were analyzed separately. MAIN
OUTCOMES AND MEASURES: Previously validated diagnosis codes were used to identify
ischemic strokes after discharge from the index hospitalization for surgery. The
primary predictor variable was atrial fibrillation newly diagnosed during the
index hospitalization, as defined by previously validated present-on-admission
codes. Patients were censored at postdischarge emergency department encounters or
hospitalizations with a recorded diagnosis of atrial fibrillation. RESULTS: Of
1,729,360 eligible patients, 24,711 (1.43%; 95% CI, 1.41%-1.45%) had new-onset
perioperative atrial fibrillation during the index hospitalization and 13,952
(0.81%; 95% CI, 0.79%-0.82%) experienced a stroke after discharge. At 1 year
after hospitalization for cardiac surgery, cumulative rates of stroke were 0.99%
(95% CI, 0.81%-1.20%) in those with perioperative atrial fibrillation and 0.83%
(95% CI, 0.76%-0.91%) in those without atrial fibrillation. At 1 year after
noncardiac surgery, cumulative rates of stroke were 1.47% (95% CI, 1.24%-1.75%)
in those with perioperative atrial fibrillation and 0.36% (95% CI, 0.35%-0.37%)
in those without atrial fibrillation. In a Cox proportional hazards analysis
accounting for potential confounders, perioperative atrial fibrillation was
associated with subsequent stroke both after cardiac surgery (hazard ratio, 1.3;
95% CI, 1.1-1.6) and noncardiac surgery (hazard ratio, 2.0; 95% CI, 1.7-2.3). The
association was significantly stronger for perioperative atrial fibrillation
after noncardiac vs cardiac surgery (P < .001 for interaction). CONCLUSIONS AND
RELEVANCE: Among patients hospitalized for surgery, perioperative atrial
fibrillation was associated with an increased long-term risk of ischemic stroke,
especially following noncardiac surgery.
PMID- 25117131
TI - Association between analytic strategy and estimates of treatment outcomes in meta
analyses.
AB - IMPORTANCE: A persistent dilemma when performing meta-analyses is whether all
available trials should be included in the meta-analysis. OBJECTIVES: To compare
treatment outcomes estimated by meta-analysis of all trials and several
alternative analytic strategies: single most precise trial (ie, trial with the
narrowest confidence interval), meta-analysis restricted to the 25% largest
trials, limit meta-analysis (a meta-analysis model adjusted for small-study
effect), and meta-analysis restricted to trials at low overall risk of bias. DATA
SOURCES: One hundred sixty-three meta-analyses published between 2008 and 2010 in
high-impact-factor journals and between 2011 and 2013 in the Cochrane Database of
Systematic Reviews: 92 (705 randomized clinical trials [RCTs]) with subjective
outcomes and 71 (535 RCTs) with objective outcomes. DATA SYNTHESIS: For each meta
analysis, the difference in treatment outcomes between meta-analysis of all
trials and each alternative strategy, expressed as a ratio of odds ratios (ROR),
was assessed considering the dependency between strategies. A difference greater
than 30% was considered substantial. RORs were combined by random-effects meta
analysis models to obtain an average difference across the sample. An ROR greater
than 1 indicates larger treatment outcomes with meta-analysis of all trials.
Subjective and objective outcomes were analyzed separately. RESULTS: Treatment
outcomes were larger in the meta-analysis of all trials than in the single most
precise trial (combined ROR, 1.13 [95% CI, 1.07-1.19]) for subjective outcomes
and 1.03 (95% CI, 1.01-1.05) for objective outcomes). The difference in treatment
outcomes between these strategies was substantial in 47 of 92 (51%) meta-analyses
of subjective outcomes (meta-analysis of all trials showing larger outcomes in
40/47) and in 28 of 71 (39%) meta-analyses of objective outcomes (meta-analysis
of all trials showing larger outcomes in 21/28). The combined ROR for subjective
and objective outcomes was, respectively, 1.08 (95% CI, 1.04-1.13) and 1.03 (95%
CI, 1.00-1.06) when comparing meta-analysis of all trials and meta-analysis of
the 25% largest trials, 1.17 (95% CI, 1.11-1.22) and 1.13 (95% CI, 0.82-1.55)
when comparing meta-analysis of all trials and limit meta-analysis, and 0.94 (95%
CI, 0.86-1.04) and 1.03 (95% CI, 1.00-1.06) when comparing meta-analysis of all
trials and meta-analysis restricted to trials at low risk of bias. CONCLUSIONS
AND RELEVANCE: Estimation of treatment outcomes in meta-analyses differs
depending on the strategy used. This instability in findings can result in major
alterations in the conclusions derived from the analysis and underlines the need
for systematic sensitivity analyses.
PMID- 25117133
TI - Youth experimentation with e-cigarettes: another interpretation of the data.
PMID- 25117132
TI - Treatment of hepatitis C: a systematic review.
AB - IMPORTANCE: Hepatitis C virus (HCV) infects more than 185 million individuals
worldwide. Twenty percent of patients chronically infected with HCV progress to
cirrhosis. New, simpler therapeutics using direct-acting antivirals that target
various stages of the HCV life cycle are in development to eradicate HCV without
concomitant interferon. OBJECTIVES: To summarize published evidence on safety,
efficacy (measured by a sustained virologic response [SVR], which is the
treatment goal of undetectable plasma HCV RNA 12 or 24 weeks after therapy
completion), and tolerability of current US Food and Drug Administration-approved
interferon-based regimens and oral interferon-free regimens used for treating HCV
infection and coinfection with human immunodeficiency virus (HIV) and HCV; to
provide treatment recommendations for specialists and generalists based on
published evidence. EVIDENCE REVIEW: A literature search of Web of Science,
Scopus, Embase, Agricola, Cochrane Library, Cinahl Plus, ClinicalTrials.gov,
Conference Papers Index, Gideon, PsycINFO, Google Scholar, and Oaister was
conducted from January 1, 2009, to May 30, 2014. Publications describing phase 2,
3, and 4 studies evaluating the treatment of HCV were included. Forty-one studies
involving 19,063 adult patients were included. Strength of clinical data and
subsequent HCV treatment recommendations were graded according to the Oxford
Centre for Evidence-Based Medicine. FINDINGS: Patients infected with HCV genotype
1 represent 60% to 75% of HCV infections in the United States. Hepatitis C virus
genotype 1 is more difficult to cure than genotype 2 or genotype 3. Patients with
HCV genotype 1 should receive treatment with sofosbuvir + pegylated interferon +
ribavirin because of the shorter duration of therapy and high rates of SVR (89%
90%). Simeprevir + pegylated interferon + ribavirin is an alternative for
patients with HCV genotype 1 (SVR, 79%-86%). Patients with HCV genotypes 2 and 3,
representing 20% to 29% of US HCV infections, should receive therapy with
sofosbuvir + ribavirin alone (SVR for genotype 2, 12 weeks' duration: 82%-93%;
SVR for genotype 3, 24 weeks' duration, 80%-95%). Patients with HIV-HCV
coinfection and patients with compensated cirrhosis (ie, cirrhosis but preserved
synthetic liver function) should receive the same treatment as HCV-monoinfected
patients. CONCLUSIONS AND RELEVANCE: New, short-duration, simpler therapies
result in high SVR rates for HCV-infected patients. In conjunction with increased
screening for HCV as suggested by recent Centers for Disease Control and
Prevention guidelines, availability of new therapies may lead to the treatment of
many more people with chronic HCV infection.
PMID- 25117134
TI - Serum ammonia level for the evaluation of hepatic encephalopathy.
PMID- 25117135
TI - Time to cardioversion for acute atrial fibrillation and thromboembolic
complications.
PMID- 25117136
TI - Risk and benefits of screening mammography.
PMID- 25117137
TI - Risk and benefits of screening mammography--reply.
PMID- 25117138
TI - Transparency in the delivery of mental health care.
PMID- 25117139
TI - Transparency in the delivery of mental health care--reply.
PMID- 25117140
TI - Hospital alarms and patient safety.
PMID- 25117141
TI - Hospital alarms and patient safety--reply.
PMID- 25117146
TI - Viral hepatitis--1975.
PMID- 25117147
TI - JAMA patient page. Hepatitis C.
PMID- 25117148
TI - Novel ABCC8 (SUR1) gene mutations in Asian Indian children with congenital
hyperinsulinemic hypoglycemia.
AB - Congenital hyperinsulinemic hypoglycemia (HI) is a heterogeneous genetic disorder
of insulin secretion characterized by persistent hypoglycemia, most commonly
associated with inactivating mutations of the beta-cell ATP-sensitive K(+)
channel (K(ATP) channel) genes ABCC8 (encoding SUR1) and KCNJ11(encoding Kir6.2).
This study aimed to screen the mutations in the genes associated with congenital
HI in Asian Indian children. Recessive mutations of these genes cause
hyperinsulinism that is unresponsive to treatment with channel agonists like
diazoxide. Dominant K(ATP) mutations have been associated with diazoxide
responsive disease. The KCNJ11, ABCC8, GCK, HNF4A, and GLUD1 genes were analyzed
by sequence analysis in 22 children with congenital HI. We found 10 novel
mutations (c.1delA, c.61delG, c.267delT, c.619-629delCCCGAGGACCT, Gln444*,
Leu724Pro, Ala847Thr, Trp898*, IVS30-2A>C, and Leu1454Arg) and two known
mutations (Gly111Arg and Arg598*) in the ABCC8 gene. This study describes novel
and known ABCC8 gene mutations in children with congenital HI. This is the first
large genetic screening study on HI in India and our results will help clinicians
in providing optimal treatment for patients with hyperinsulinemia and in
assisting affected families with genetic counseling.
PMID- 25117149
TI - Likelihood ratio tests in rare variant detection for continuous phenotypes.
AB - It is believed that rare variants play an important role in human phenotypes;
however, the detection of rare variants is extremely challenging due to their
very low minor allele frequency. In this paper, the likelihood ratio test (LRT)
and restricted likelihood ratio test (ReLRT) are proposed to test the association
of rare variants based on the linear mixed effects model, where a group of rare
variants are treated as random effects. Like the sequence kernel association test
(SKAT), a state-of-the-art method for rare variant detection, LRT and ReLRT can
effectively overcome the problem of directionality of effect inherent in the
burden test in practice. By taking full advantage of the spectral decomposition,
exact finite sample null distributions for LRT and ReLRT are obtained by
simulation. We perform extensive numerical studies to evaluate the performance of
LRT and ReLRT, and compare to the burden test, SKAT and SKAT-O. The simulations
have shown that LRT and ReLRT can correctly control the type I error, and the
controls are robust to the weights chosen and the number of rare variants under
study. LRT and ReLRT behave similarly to the burden test when all the causal rare
variants share the same direction of effect, and outperform SKAT across various
situations. When both positive and negative effects exist, LRT and ReLRT suffer
from few power reductions compared to the other two competing methods; under this
case, an additional finding from our simulations is that SKAT-O is no longer the
optimal test, and its power is even lower than that of SKAT. The exome sequencing
SNP data from Genetic Analysis Workshop 17 were employed to illustrate the
proposed methods, and interesting results are described.
PMID- 25117150
TI - ABCC5 transporter is a novel type 2 diabetes susceptibility gene in European and
African American populations.
AB - Numerous functional studies have implicated PARL in relation to type 2 diabetes
(T2D). We hypothesised that conflicting human association studies may be due to
neighbouring causal variants being in linkage disequilibrium (LD) with PARL. We
conducted a comprehensive candidate gene study of the extended LD genomic region
that includes PARL and transporter ABCC5 using three data sets (two European and
one African American), in relation to healthy glycaemic variation, visceral fat
accumulation and T2D disease. We observed no evidence for previously reported T2D
association with Val262Leu or PARL using array and fine-map genomic and
expression data. By contrast, we observed strong evidence of T2D association with
ABCC5 (intron 26) for European and African American samples (P = 3E-07) and with
ABCC5 adipose expression in Europeans [odds ratio (OR) = 3.8, P = 2E-04]. The
genomic location estimate for the ABCC5 functional variant, associated with all
phenotypes and expression data (P = 1E-11), was identical for all samples (at
Chr3q 185,136 kb B36), indicating that the risk variant is an expression
quantitative trait locus (eQTL) with increased expression conferring risk of
disease. That the association with T2D is observed in populations of disparate
ancestry suggests the variant is a ubiquitous risk factor for T2D.
PMID- 25117152
TI - On the reliability of NMR relaxation data analyses: a Markov Chain Monte Carlo
approach.
AB - The analysis of NMR relaxation data is revisited along the lines of a Bayesian
approach. Using a Markov Chain Monte Carlo strategy of data fitting, we
investigate conditions under which relaxation data can be effectively interpreted
in terms of internal dynamics. The limitations to the extraction of kinetic
parameters that characterize internal dynamics are analyzed, and we show that
extracting characteristic time scales shorter than a few tens of ps is very
unlikely. However, using MCMC methods, reliable estimates of the marginal
probability distributions and estimators (average, standard deviations, etc.) can
still be obtained for subsets of the model parameters. Thus, unlike more
conventional strategies of data analysis, the method avoids a model selection
process. In addition, it indicates what information may be extracted from the
data, but also what cannot.
PMID- 25117151
TI - The efficacy of pad placement for electrical cardioversion of atrial
fibrillation/flutter: a systematic review.
AB - OBJECTIVES: Electrical cardioversion is commonly used to treat patients with
atrial fibrillation and atrial flutter to restore normal sinus rhythm. There has
been considerable debate as to whether the electrode placement affects the
efficacy of electrical cardioversion. The objective of this study was to examine
the effectiveness of anteroposterior (A-P) versus anterolateral (A-L) electrode
placement to restore normal sinus rhythm. METHODS: A search of eight electronic
databases, including Medline, EMBASE, CINAHL, and Cochrane was completed. Grey
literature (hand-searching, Google, and SCOPUS) searching was also conducted.
Studies were included if they were controlled clinical trials comparing the
effectiveness of A-P versus A-L pad placement to restore normal sinus rhythm in
adult patients with atrial fibrillation and flutter. Two independent reviewers
judged study relevance, inclusion, and quality (e.g., risk of bias). Individual
and pooled statistics were calculated as relative risks (RRs) with 95% confidence
intervals (CIs) using a random-effects model, and heterogeneity (I(2) ) was
reported. RESULTS: From 788 citations, 13 studies were included; seven involved
monophasic, five involved biphasic, and one analyzed both waveform devices. The
included studies tended to report cumulative success rates to restoring normal
sinus rhythm after one to five sequential shocks of increasing energy; the number
of shocks and energy used differed among studies. The risk of bias of the studies
was "unclear." After the first shock, pad placement was not associated with an
increased likelihood of restoring normal sinus rhythm (RR = 0.88; 95% CI = 0.73
to 1.06); however, heterogeneity was high (I(2) = 63%). Subgroup comparisons
revealed that the A-L position was more effective (RR = 0.77; 95% CI = 0.59 to
1.00) at restoring normal sinus rhythm when using biphasic shocks (comparison p =
0.04). Overall, the pooled results failed to identify a difference between A-P
and A-L pad placement in restoring normal sinus rhythm at any time (RR = 1.00;
95% CI = 0.95 to 1.05); however, heterogeneity was high (I(2) = 61%). No
significant subgroup differences were found. Side effects were reported in only
three studies. CONCLUSIONS: The published literature is restricted to persistent
atrial fibrillation and atrial flutter, pad placement varied, and energy levels
used were lower than currently recommended; however, the accumulated evidence
suggests that electrical pad placement is not a critically important factor in
successful cardioversion in atrial fibrillation and flutter (AF/AFL). A trial is
urgently needed in recent-onset atrial fibrillation and atrial flutter patients
using biphasic devices and high energy levels to resolve the debate.
PMID- 25117153
TI - Dermatological toxicity associated with targeted therapies in cancer: optimal
management.
AB - Targeted therapies have developed rapidly over the last few years in the field of
oncology thanks to a better understanding of carcinogenesis. They target pathways
involved in signal transduction (EGFR, HER2, HER3, HER4, FLT3, RAS, RAF, MEK,
KIT, RET, mTOR, SRC, EPH, SCF), tumor angiogenesis (VEGFR, TIE2), and tumor
microenvironment (PDGFR, FGFR). They rarely cause the systemic adverse reactions
generally associated with chemotherapy, but frequently cause disabling and
specific skin toxicity. The impact on patient quality of life can be important
both in terms of symptoms caused and of potentially aesthetic consequences.
Inappropriate management can increase the risk of dose reduction or
discontinuation of the cancer treatment. In this review, we will discuss skin
toxicity associated with the main drug classes-EGFR, BRAF, MEK, mTOR, c-KIT,
CTLA4, and SMO inhibitors, and anti-angiogenic agents. Targeted therapy-induced
skin toxicities will be detailed in terms of symptoms, frequency, evolution,
complications, and topical and oral treatments in order to improve their
diagnosis and management.
PMID- 25117154
TI - Neonatal junctional epidermolysis bullosa: treatment conundrums and ethical
decision making.
AB - Junctional epidermolysis bullosa (JEB), generalized severe (previously called
JEB, Herlitz-type) has an extremely poor prognosis, with a mean age of death at 5
months old and most dead before age 3 years. We describe a typical case of a
neonate with JEB who developed failure to thrive before his death from fungal
septicemia at 4 months of age. This case highlights the ethical considerations of
invasive treatments such as gastrostomy tube placements, intubations, and central
line placements in neonates with JEB. We review the literature as well as discuss
the ethical conundrums in the care of patients with JEB and other severe forms of
epidermolysis bullosa.
PMID- 25117156
TI - Mechanisms of action of oral emergency contraception.
AB - This review gives an overview of the mechanisms of action of oral emergency
contraception pills (ECPs), focusing on the levonorgestrel (LNG) and ulipristal
acetate (UPA) containing ECPs. In vivo and in vitro studies have addressed the
effect of EC on various possible targets. Based on these studies as well as on
clinical trials it is clear that the efficacy of ECPs to prevent an unintended
pregnancy depends on their mechanism of action as well as on their use in
relation to the fertile window. While the main effect of both available ECPs is
to prevent or delay ovulation the window of action for UPA is wider than that of
LNG. This provides the biological explanation for the difference observed in
clinical trials and the higher efficacy of UPA. Neither LNG nor UPA impairs
endometrial receptivity or embryo implantation. Correct knowledge on the
mechanism of action of ECPs is important to avoid overestimating their
effectiveness and to advise women on correct use.
PMID- 25117158
TI - Optimal older adult emergency care: introducing multidisciplinary geriatric
emergency department guidelines from the American College of Emergency
Physicians, American Geriatrics Society, Emergency Nurses Association, and
Society for Academic Emergency Medicine.
AB - In the United States and around the world, effective, efficient, and reliable
strategies to provide emergency care to aging adults is challenging crowded
emergency departments (EDs) and a strained health care system. In response,
geriatric emergency medicine (EM) clinicians, educators, and researchers
collaborated with the American College of Emergency Physicians (ACEP), American
Geriatrics Society (AGS), Emergency Nurses Association (ENA), and the Society for
Academic Emergency Medicine (SAEM) to develop guidelines intended to improve ED
geriatric care by enhancing expertise, educational, and quality improvement
expectations; equipment; policies; and protocols. These "Geriatric Emergency
Department Guidelines" represent the first formal society-led attempt to
characterize the essential attribute of the geriatric ED and received formal
approval from the boards of directors for each of the four societies in 2013 and
2014. This article is intended to introduce EM and geriatric health care
providers to the guidelines, while providing proposals for educational
dissemination, refinement via formal effectiveness evaluations and cost
effectiveness studies, and institutional credentialing.
PMID- 25117155
TI - Hand sanitiser provision for reducing illness absences in primary school
children: a cluster randomised trial.
AB - BACKGROUND: The potential for transmission of infectious diseases offered by the
school environment are likely to be an important contributor to the rates of
infectious disease experienced by children. This study aimed to test whether the
addition of hand sanitiser in primary school classrooms compared with usual hand
hygiene would reduce illness absences in primary school children in New Zealand.
METHODS AND FINDINGS: This parallel-group cluster randomised trial took place in
68 primary schools, where schools were allocated using restricted randomisation
(1:1 ratio) to the intervention or control group. All children (aged 5 to 11 y)
in attendance at participating schools received an in-class hand hygiene
education session. Schools in the intervention group were provided with alcohol
based hand sanitiser dispensers in classrooms for the winter school terms (27
April to 25 September 2009). Control schools received only the hand hygiene
education session. The primary outcome was the number of absence episodes due to
any illness among 2,443 follow-up children whose caregivers were telephoned after
each absence from school. Secondary outcomes measured among follow-up children
were the number of absence episodes due to specific illness (respiratory or
gastrointestinal), length of illness and illness absence episodes, and number of
episodes where at least one other member of the household became ill subsequently
(child or adult). We also examined whether provision of sanitiser was associated
with experience of a skin reaction. The number of absences for any reason and the
length of the absence episode were measured in all primary school children
enrolled at the schools. Children, school administrative staff, and the school
liaison research assistants were not blind to group allocation. Outcome assessors
of follow-up children were blind to group allocation. Of the 1,301 and 1,142
follow-up children in the hand sanitiser and control groups, respectively, the
rate of absence episodes due to illness per 100 child-days was similar (1.21 and
1.16, respectively, incidence rate ratio 1.06, 95% CI 0.94 to 1.18). The
provision of an alcohol-based hand sanitiser dispenser in classrooms was not
effective in reducing rates of absence episodes due to respiratory or
gastrointestinal illness, the length of illness or illness absence episodes, or
the rate of subsequent infection for other members of the household in these
children. The percentage of children experiencing a skin reaction was similar
(10.4% hand sanitiser versus 10.3% control, risk ratio 1.01, 95% CI 0.78 to
1.30). The rate or length of absence episodes for any reason measured for all
children also did not differ between groups. Limitations of the study include
that the study was conducted during an influenza pandemic, with associated public
health messaging about hand hygiene, which may have increased hand hygiene among
all children and thereby reduced any additional effectiveness of sanitiser
provision. We did not quite achieve the planned sample size of 1,350 follow-up
children per group, although we still obtained precise estimates of the
intervention effects. Also, it is possible that follow-up children were healthier
than non-participating eligible children, with therefore less to gain from
improved hand hygiene. However, lack of effectiveness of hand sanitiser provision
on the rate of absences among all children suggests that this may not be the
explanation. CONCLUSIONS: The provision of hand sanitiser in addition to usual
hand hygiene in primary schools in New Zealand did not prevent disease of
severity sufficient to cause school absence. TRIAL REGISTRATION: Australian New
Zealand Clinical Trials Registry ACTRN12609000478213. Please see later in the
article for the Editors' Summary.
PMID- 25117159
TI - Non-infectious skin disease in Indigenous Australians.
AB - The burden of non-infectious skin disease in the Indigenous Australian population
has not been previously examined. This study considers the published data on the
epidemiology and clinical features of a number of non-infectious skin diseases in
Indigenous Australians. It also outlines hypotheses for the possible differences
in the prevalence of such diseases in this group compared with the general
Australian population. There is a paucity of literature on the topic but, from
the material available, Indigenous Australians appear to have a reduced
prevalence of psoriasis, type 1 hypersensitivity reactions and skin cancer but
increased rates of lupus erythematosus, kava dermopathy and vitamin D deficiency
when compared to the non-Indigenous Australian population. This article profiles
the prevalence and presentation of non-infectious skin diseases in the Indigenous
Australian population to synthesise our limited knowledge and highlight
deficiencies in our understanding.
PMID- 25117160
TI - Surgical gem: island advancement flaps for lip reconstruction.
AB - Island advancement flaps provide specific advantages for repairing certain
defects on the upper lip. We discuss the design and execution of this flap for
defects on the alar sill and philtrum.
PMID- 25117161
TI - A case of abatacept associated neutrophilic dermatosis and a review of the
literature.
AB - Abatacept is a novel biological agent that dampens the immune response by
blocking the co-stimulation of T-cells, thus downregulating T-cell activation. It
is currently approved for the treatment of rheumatoid arthritis (RA). The group
of novel immunomodulatory agents, referred to as biologics, have now been used
extensively, with established safety and side-effect profiles. There are,
however, increasing reports of adverse paradoxical reactions, most notably
resulting from anti-tumour necrosis factor (TNF) therapy. While cutaneous adverse
reactions to abatacept are rare, there are a few reports of such paradoxical
reactions. We report a case of an idiosyncratic paradoxical neutrophilic
dermatosis associated with the use of abatacept.
PMID- 25117162
TI - Emergence of chemoresistance in a metastatic basal cell carcinoma patient after
complete response to hedgehog pathway inhibitor vismodegib (GDC-0449).
AB - Vismodegib (GDC-0449, Genentech, USA), a small molecule inhibitor of the Hedgehog
signalling pathway, has potent anti-tumour activity in advanced basal cell
carcinoma (BCC). We report a case of a 67-year-old Australian man with metastatic
BCC including pulmonary disease with malignant effusion who showed a dramatic
complete response to vismodegib but subsequently experienced a recurrence of
pulmonary disease, indicative of chemoresistance to vismodegib. This case is the
first to illustrate chemoresistance in a patient with metastatic BCC, and
demonstrates the need for closely monitoring metastatic BCC patients even after
an apparently complete response.
PMID- 25117163
TI - Isotretinoin and night blindness.
AB - Isotretinoin is an effective and increasingly popular treatment for acne
vulgaris. There have been reports of night blindness as a side-effect of
treatment although the evidence does not demonstrate a clear causal relationship
between isotretinoin therapy and the risk of night blindness. Nevertheless,
considering the lack of evidence in this area, it is important to educate
patients about this potential consequence, which may become longstanding and even
irreversible, and encourage them to promptly report changes in their night
vision.
PMID- 25117165
TI - Montague B Lewis.
PMID- 25117166
TI - Abdomino-pelvic actinomycetoma successfully treated with combination
chemotherapy.
PMID- 25117167
TI - A novel mutation of CYLD gene in a Chinese family with multiple familial
trichoepithelioma.
PMID- 25117168
TI - Delayed onset perforating folliculitis associated with sorafenib.
PMID- 25117169
TI - Pregnancy outcomes of two patients exposed to ustekinumab in the first trimester.
PMID- 25117170
TI - Pretibial fever: a forgotten cause of erythema nodosum.
PMID- 25117171
TI - Comedonal Darier's disease diagnosed incidentally in a patient undergoing a
routine skin examination for sun cancer.
PMID- 25117172
TI - Involvement of oxidative stress in the mechanism of cadmium-induced toxicity on
rat uterus.
AB - The study was undertaken to explore whether cadmium bioaccumulation can induce
oxidative stress in the uterus of rats. Cadmium (0.09, 0.9, 1.8 or 4.5mgCd/kg
b.w.) was administered by gavage for 28 days. The animals were dissected on the
first day and then after 90 days post exposure (second group of animals). The
results show that cadmium accumulates in the uterus in a dose-dependent manner.
The uterine Cd concentrations were almost the same in both groups, which is
indicative of its long half-life in this organ. The accumulated cadmium caused
significant changes in catalase (CAT) activity and lipid peroxidation (MDA)
levels at concentrations from 0.09 to 0.35MUgCd/g wet uterine tissue. In summary
our results show that the induction of oxidative stress and lipid peroxidation in
the uterus may play important roles in the mechanism of toxicity in this organ
and may have a negative impact on reproductive processes.
PMID- 25117174
TI - Can enrichment make Brazilian tapir spend more time on view to the public?
AB - One common visitor complaint in zoos is that the nonhuman animals are not
visible. This problem needs to be resolved without compromising the animals'
welfare; environmental enrichment could solve the problem. This study
investigated whether enrichment would increase public exposure time of lowland
tapir (Tapirus terrestris) in the Belo Horizonte Zoo in Minas Gerais, Brazil.
Observations were made before (62 hr) and during (62 hr) the introduction of
enrichment using focal animal sampling with instantaneous recording of behavior.
The 5 enrichment items were a bamboo fence covered in vines, logs, a sandbox, dry
leaves, and bamboo bushes. Before the enrichments were applied, the tapir was not
visible to the public for more than 85% of the time. In addition, during the
analysis of the enrichment treatment, other variables were considered--such as
weekday, time of day, and weather conditions--which could influence the animals'
interaction with the enrichments. The enrichments increased and decreased the
expression of some behaviors; however, public viewing time of the animals did not
increase. Thus, the enrichment applied was not strong enough to overcome the
animals' crepuscular behavior.
PMID- 25117173
TI - The pharmacokinetics of daclatasvir and asunaprevir administered in combination
in studies in healthy subjects and patients infected with hepatitis C virus.
AB - BACKGROUND AND OBJECTIVES: The combination of direct-acting antiviral agents in
patients with chronic hepatitis C virus (HCV) infection has demonstrated clinical
benefit; however, evaluation of potential drug-drug interactions is required
prior to therapy. METHODS: An open-label study assessed the pharmacokinetics and
tolerability of the HCV NS5A replication complex inhibitor daclatasvir and the
HCV NS3 protease inhibitor asunaprevir when co-administered in healthy subjects.
Daclatasvir 60 mg once daily and asunaprevir 600 mg twice daily were dosed for 7
days alone followed by combination dosing for 14 days at 30 mg once daily and 200
mg twice daily, respectively. Further assessments were provided comparing
exposures from the current study with those from studies in HCV-infected patients
receiving either the same or higher doses of daclatasvir or asunaprevir
administered alone or together. RESULTS: Dose-normalized daclatasvir and
asunaprevir morning exposures were comparable with control in healthy subjects,
with geometric mean area under the concentration-time curve ratios of 1.202 (90 %
CI 1.113-1.298) and 0.868 (90 % CI 0.726-1.038), respectively. In HCV patients
daclatasvir and asunaprevir exposures were largely comparable, when administered
together or alone. CONCLUSIONS: Additional data support the conclusion that there
is no clinically meaningful interaction between daclatasvir and asunaprevir in
either healthy subjects or HCV-infected patients, including those also receiving
peginterferon-alpha/ribavirin, and that the combination of daclatasvir 60 mg once
daily and asunaprevir 200 mg twice daily is generally well-tolerated.
PMID- 25117175
TI - A case of painless acute Type-A thoracic aortic dissection.
AB - We describe the case of an 83-year-old lady with a known aneurysmal thoracic
aorta, developing acute breathlessness and hypoxia, with no pain and unremarkable
cardiovascular examination. As D-dimers were raised, she was treated with low
molecular-weight heparin (LMWH) for suspected pulmonary embolism. CT pulmonary
angiography showed acutely dissecting, Type-A, thoracic aortic aneurysm. The
patient was treated medically with beta-blockers. Despite a poor prognosis, she
remains well 2 months later. Observational studies of patients over 70 with Type
A dissection show only 75.3% experience pain, are offered surgery less and have
higher mortality. d-Dimers are almost always elevated in aortic dissection. No
previous studies document breathlessness as the only presenting symptom. This
case emphasises the need, in older populations, for a low suspicion threshold for
aortic dissection.
PMID- 25117176
TI - Individualized quality of life in patients with low back pain: reliability and
validity of the Patient Generated Index.
AB - OBJECTIVE: To evaluate the reliability and validity of the improved version of
the Patient Generated Index (PGI) in patients with low back pain. METHODS: The
PGI was administered to 90 patients attending care in 1 of 6 institutions in
Norway and evaluated for reliability and validity. The questionnaire was given
out to 61 patients for re-test purposes. RESULTS: The PGI was completed correctly
by 80 (88.9%) patients and, of the 61 patients responding to the re-test, 50
(82.0%) completed both surveys correctly. PGI scores were approximately normally
distributed, with a median of 40 (range 80), where 100 is the best possible
quality of life. There were no floor or ceiling effects. The 5 most frequently
listed areas affecting quality of life were pain, sleep, stiffness, socializing
and housework. The test-retest intraclass correlation coefficient was 0.73. The
smallest detectable changes for individual and group purposes were 32.8 and 4.6,
respectively. The correlations between PGI scores and other instrument scores
followed a priori hypotheses of low to moderate correlations. DISCUSSION: The PGI
has evidence for reliability and validity in Norwegian patients with low back
pain at the group level and may be considered for application in intervention
studies when a comprehensive evaluation of quality of life is important. However,
the smallest detectable change, of approximately 30 points, may be considered too
large for individual purposes in clinical applications.
PMID- 25117178
TI - Heart failure: gaps in knowledge and failures in treatment.
AB - Please see later in the article for the Editors' Summary.
PMID- 25117180
TI - Seniors' body weight dissatisfaction and longitudinal associations with weight
changes, anorexia of aging, and obesity: results from the NuAge Study.
AB - OBJECTIVE: We examined longitudinal associations between weight dissatisfaction,
weight changes, anorexia of aging, and obesity among 1,793 seniors followed over
4 years between 2003 and 2009. METHOD: Obesity prevalence (body mass index [BMI]
>= 30) and prevalence/incidence of weight dissatisfaction, anorexia of aging
(self-reported appetite loss), and weight changes >=5% were assessed. Predictors
of weight loss >=5%, anorexia of aging, and weight dissatisfaction were examined
using logistic regressions. RESULTS: Half of seniors experienced weight
dissatisfaction (50.6%, 95% confidence interval [CI] = [48.1, 53.1]). Anorexia of
aging and obesity prevalence was 7.0% (95% CI = [5.7, 8.3]) and 25.1% (95% CI =
[22.9, 27.3]), whereas incidence of weight gain/loss >=5% was 6.6% (95% CI =
[1.3, 11.9]) and 8.8% (95% CI = [3.3, 14.3]). Weight gain >=5% predicts men's
subsequent weight dissatisfaction (odds ratio [OR] = 6.66, 95% CI = [2.06,
21.60]). No other association was observed. DISCUSSION: Weight dissatisfaction is
frequent but not associated with subsequent eating disorders. In men, weight gain
predicted weight dissatisfaction. Seniors' weight dissatisfaction does not
necessarily equate weight changes. Due to its high prevalence, it is of public
health interest to understand how seniors' weight dissatisfaction may impact
health.
PMID- 25117181
TI - Predictors of injurious falls and fear of falling differ: an 11-year longitudinal
study of incident events in older people.
AB - OBJECTIVE: The objective of the study is to identify the intrinsic, psychosocial
and lifestyle factors, which, over time, predict the incidence of having a fall
requiring medical attention (injurious fall) or of acquiring a fear of falling
(FOF). METHOD: Data from 1,000 participants in the Melbourne Longitudinal Studies
on Healthy Ageing (MELSHA, 1994-2005) were analyzed using cox regressions and
hazard ratios. RESULTS: The predictors of injurious falls (n = 900, events = 200)
were increasing age, slower gait speed, and being depressed. Main predictors of
developing a FOF (n = 855, events =117) were increasing age, cognitive
impairment, reduced social activity, and gender. A history of falls at baseline
did not predict acquiring a FOF nor did FOF predict a future fall. DISCUSSION:
The profile of the person who will have an injurious fall differs from the
profile of the person who develops a FOF and should be considered when designing
interventions.
PMID- 25117182
TI - Untargeted mass spectrometry-based metabolomic profiling of pleural effusions:
fatty acids as novel cancer biomarkers for malignant pleural effusions.
AB - Untargeted mass spectrometry-based metabolomic profiling is a powerful analytical
method used for broad-spectrum identification and quantification of metabolites
in biofluids in human health and disease states. In this study, we exploit
metabolomic profiling for cancer biomarker discovery for diagnosis of malignant
pleural effusions. We envisage the result will be clinically useful since
currently there are no cancer biomarkers that are accurate enough for the
diagnosis of malignant pleural effusions. Metabolomes of 32 malignant pleural
effusions from lung cancer patients and 18 benign effusions from patients with
pulmonary tuberculosis were analyzed using reversed-phase liquid chromatography
tandem mass spectrometry (LC-MS/MS) using AB SCIEX TripleTOF 5600. MS spectra
were analyzed using XCMS, PeakView, and LipidView. Metabolome-Wide Association
Study (MWAS) was performed by Receiver Operating Characteristic Curve Explorer
and Tester (ROCCET). Insignificant markers were filtered out using a metabolome
wide significance level (MWSL) with p-value < 2 * 10(-5) for t test. Only
compounds in Human Metabolome Database (HMDB) will be used as cancer biomarkers.
ROCCET analysis of ESI positive and negative MS spectra revealed free fatty acid
(FFA) 18:1 (oleic acid) had the largest area-under-ROC of 0.96 (95% CI = 0.87
1.00) in malignant pleural effusions. Using a ratio of FFA 18:1-to-ceramide
(d18:1/16:0), the area-under-ROC was further increased to 0.99 (95% CI = 0.91
1.00) with sensitivity 93.8% and specificity 100.0%. Using untargeted metabolomic
profiling, the diagnostic cancer biomarker with the largest area-under-ROC can be
determined objectively. This lipogenic phenotype could be explained by
overexpression of fatty acid synthase (FASN) in cancer cells. The diagnostic
performance of FFA 18:1-to-ceramide (d18:1/16:0) ratio supports its use for
diagnosis of malignant pleural effusions.
PMID- 25117185
TI - What do people want? Factors people consider when acquiring dogs, the complexity
of the choices they make, and implications for nonhuman animal relocation
programs.
AB - A survey was conducted to assess decisions people make when acquiring dogs,
including what sources they consider, the importance of the variety of dogs
available, and their willingness to travel to adopt dogs of their choice. A
conjoint design was used to ask each respondent to rate his or her likelihood of
acquiring a dog based on a "profile" that included attributes such as age, size,
and color as well as where the dog came from and euthanasia risk. Overall, these
results showed that people preferred variety and would drive distances to get
dogs of their choice. The findings revealed that no single attribute drove
choice, indicating that people have complex preferences and these vary widely
across individuals. Nonhuman animal shelters may be able to increase their
adoption rates by providing more variety and not just dogs typically thought of
as "in demand" but those who represent a range of diversity through the
utilization of animal relocation programs.
PMID- 25117183
TI - Pharmacokinetic evaluations of the co-administrations of vandetanib and
metformin, digoxin, midazolam, omeprazole or ranitidine.
AB - BACKGROUND AND OBJECTIVE: Vandetanib is a selective inhibitor of vascular
endothelial growth factor receptor (VEGFR), epidermal growth factor receptor
(EGFR) and rearranged during transfection (RET) signalling, indicated for the
treatment of medullary thyroid cancer. We investigated potential drug-drug
interactions between vandetanib and metformin [organic cation transporter 2
(OCT2) substrate; NCT01551615]; digoxin [P-glycoprotein (P-gp) substrate;
NCT01561781]; midazolam [cytochrome P450 (CYP) 3A4 substrate; NCT01544140];
omeprazole (proton pump inhibitor) or ranitidine (histamine H2-receptor
antagonist; both NCT01539655). METHODS: Four open-label, phase I studies were
conducted in healthy volunteers: n = 14 (metformin), n = 14 (digoxin), n = 17
(midazolam), n = 16 (omeprazole), n = 18 (ranitidine). Three of these comprised
the following regimens: metformin 1000 mg +/- vandetanib 800 mg, midazolam 7.5 mg
+/- vandetanib 800 mg, or digoxin 0.25 mg +/- vandetanib 300 mg. The randomized
study comprised vandetanib 300 mg alone and then either (i) omeprazole 40 mg
(days 1-4), and omeprazole + vandetanib (day 5); or (ii) ranitidine 150 mg (day
1), and ranitidine + vandetanib (day 2). The primary objective assessed
metformin, digoxin, midazolam and vandetanib pharmacokinetics. RESULTS:
Vandetanib + metformin increased metformin area under the plasma concentration
time curve from zero to infinity (AUC0-infinity) and maximum observed plasma
concentration (Cmax) by 74 and 50 %, respectively, and decreased the geometric
mean metformin renal clearance (CLR) by 52 % versus metformin alone. Vandetanib +
digoxin increased digoxin area under the concentration-time curve from zero to
the last quantifiable concentration (AUC0-last) and Cmax by 23 and 29 %,
respectively, versus digoxin alone, with only a 9 % decrease in CLR. Vandetanib
had no effect on midazolam exposure. Vandetanib exposure was unchanged during co
administration with omeprazole/ranitidine. Treatment combinations were generally
well tolerated. CONCLUSION: Patients receiving vandetanib with metformin/digoxin
may require additional monitoring of metformin/digoxin, with dose adjustments
where necessary. Vandetanib with CYP3A4 substrates or omeprazole/ranitidine is
unlikely to result in clinically relevant drug-drug interactions.
PMID- 25117186
TI - Caesarean delivery: truths and consequences.
PMID- 25117184
TI - Vancomycin pharmacokinetic and pharmacodynamic models for critically ill patients
with post-sternotomy mediastinitis.
AB - BACKGROUND AND OBJECTIVE: Vancomycin is commonly used to treat serious
methicillin-resistant staphylococcal infections, especially post-sternotomy
mediastinitis (PSM). However, information on pharmacokinetics and
pharmacodynamics in intensive care unit (ICU) patients remains scarce. We
conducted vancomycin pharmacokinetic-pharmacodynamic modeling for ICU patients
with PSM. METHODS: This cohort study included 30 consecutive patients who
received multiple vancomycin doses during primary closed drainage of PSM with
Redon catheters, targeting serum drug trough concentrations of 25-35 mg/L, and
generating 359 serum vancomycin concentration-time values for analysis.
Population pharmacodynamics served to describe the withdrawal of Redon catheters,
i.e., the probability of in-ICU cure. RESULTS: Vancomycin pharmacokinetics
corresponded to a two-compartment open model with first-order elimination
kinetics. Mean [between-subject variability] population estimates were 1.91
(men)/1.25 (women) [0.28] L/h for vancomycin elimination, with intercompartmental
clearance of 5.71 [1.01] L/h, and respective central and peripheral distribution
volumes of 21.9 and 68 [0.53] L. Vancomycin clearance increased with body weight
and declined with severity at ICU admission and serum creatinine (SCr), thereby
allowing the prediction of the vancomycin plateau. Intercompartmental clearance
decreased with diabetes mellitus (-70 %). The probability of withdrawing all
Redon catheters (patient cured) was dependent only on the area under the
concentration-time curve to minimum inhibitory concentration (AUC/MIC) exposures
ratio in plasma. Neither preoperative factors, antistaphylococcal co-treatments,
nor the initial number of Redon catheters significantly influenced this
probability. The AUC/MIC exposures ratio had no significant effect on SCr levels.
CONCLUSION: These modeling analysis results identified five clinically relevant
covariates that influenced vancomycin pharmacokinetics and might achieve better
individualization of vancomycin dosing for methicillin-resistant staphylococcal
PSM in ICU patients.
PMID- 25117187
TI - The CROWN Initiative: journal editors invite researchers to develop core outcomes
in women's health.
PMID- 25117188
TI - Improving VBAC rates: the combined impact of two management strategies.
AB - BACKGROUND: Caesarean section rates in Australia have risen to >30%, with repeat
caesarean delivery the most common indication. One method of reducing caesarean
delivery rates is to increase rates of vaginal birth after caesarean section
(VBAC). AIMS: To determine the combined effect of two management strategies on
the rates of successful VBAC in women experiencing their first pregnancy
following primary caesarean section. METHODS: Prospective cohort study from May
2009 to October 2010 at a metropolitan Australian teaching hospital. The
strategies studied were (i) allocating responsibility for VBAC candidates
attempting labour to the hospital's three high-risk obstetric consultants and
(ii) implementing a next birth after caesarean (NBAC) antenatal clinic designed
to counsel and support women deciding on mode of birth for their next pregnancy
after a primary caesarean section. Data were collected from Obstetrix, a NBAC
logbook and medical records of 396 eligible women who gave birth during the study
period. RESULTS: Overall VBAC rates improved from 17.2% in 2006 prior to
implementation of the combined strategies, to 27.0% over the studied period (P <
0.001). Of those women who desired and attempted a VBAC, the success rate was
64.4%. Regression analysis identified an increased likelihood of attempted
vaginal birth where malpresentation was the indication for previous caesarean,
while Eastern Asian ethnicity was associated with increased likelihood of
choosing repeat caesarean. CONCLUSIONS: A dedicated NBAC clinic and more
consistent approach to labour management can help improve VBAC rates. Further
targeted counselling towards women with previous malpresentation and/or East
Asian descent may further improve VBAC attempt rates.
PMID- 25117189
TI - Perineal outcome and the risk of pelvic floor dysfunction: a cohort study of
primiparous women.
AB - BACKGROUND: Pelvic floor dysfunction (PFD) is the most common complication of
childbirth. Assumptions have been made that perineal trauma increases the risk of
PFD compared to an intact perineum, however the evidence for this is lacking. The
aim of this study was to explore the relationship between perineal outcome and
postpartum PFD. MATERIALS AND METHODS: Prospective cohort study design, with a
self-reported quality of life (QOL) questionnaire mailed to all primiparous women
with a non-instrumental delivery at The Townsville Hospital between 2011 and 2012
(n = 766). ANOVA was used to compare how the symptoms of PFD affect QOL in women
with an intact perineum, episiotomy or spontaneous tear. RESULTS: Seventy-nine
percent of the population had perineal injury; 60% had a spontaneous tear and 19%
had an episiotomy. Ninety-seven percent of women who completed the questionnaire
(n = 196) complained of PFD symptoms. Women with episiotomy had the best QOL,
reporting the lowest levels of urinary dysfunction (statistically significant).
No differences between the groups were found for symptoms of bowel, prolapse or
sexual dysfunction. CONCLUSIONS: This study shows a relationship between perineal
outcome and PFD and suggests that an episiotomy is associated with the least
morbidity due to symptoms of urinary incontinence. Additional large-scale
prospective research is required to further investigate and delineate the impact
of childbirth on PFD.
PMID- 25117190
TI - Teetering near the edge; women's experiences of anal incontinence following
obstetric anal sphincter injury: an interpretive phenomenological research study.
AB - BACKGROUND: Obstetric anal sphincter injury (OASIS) following vaginal delivery
increases the risk of anal incontinence (AI). Subsequent vaginal delivery and
ageing increase the risk of worsening symptoms. Very little literature describes
any in-depth understanding of what it is like to live with AI following a history
of known OASIS. AIM: To describe and interpret women's experience of AI following
OASIS and its impact on quality of life. METHODS: An interpretive
phenomenological study was conducted in a level 2 tertiary hospital in South
Australia. Women with a history of OASIS and AI were purposefully recruited. The
St Marks Vaizey score was utilised to identify symptom severity. Semi-structured
open-ended interviews were conducted, and data were analysed utilising Van Manen
thematic analysis. RESULTS: Participants (n = 10) aged 26-56 years. All women
were symptomatic of AI following OASIS, and 80% had received a primary OASIS at
their first vaginal delivery. The St Marks Vaizey score mean was 9.1 (range
within 4-22). Three essential themes grieving for loss, silence, striving for
normality with eight subthemes identified a significant sense of loss and
psychological impact of AI for this group of women. CONCLUSION: Health
professionals require a greater understanding of the negative impact of OASIS and
AI on women's quality of life. This may improve the management, education and
clinical care of this condition which may result as a consequence of OASIS.
PMID- 25117191
TI - Offering HPV vaccination to women treated for high-grade cervical intra
epithelial neoplasia: what do you need to know?
PMID- 25117192
TI - Caution regarding first trimester screening for pre-eclampsia.
PMID- 25117193
TI - Re: New directions in the prediction of pre-eclampsia.
PMID- 25117194
TI - Re: New directions in the prediction of pre-eclampsia.
PMID- 25117195
TI - The Accuracy of Template-Guided Refill Technique of Intrathecal Pumps Controlled
by Fluoroscopy: An Observational Study.
AB - OBJECTIVES: Intrathecal drug therapy is being utilized increasingly for the
treatment of chronic refractory pain. However, performing the regular pump refill
procedures caries the potential risk of medication injection into the
subcutaneous tissue. The aim of this study was to assess the accuracy of this
template-guided refill technique by means of fluoroscopic evaluation. MATERIALS
AND METHODS: In 23 patients, the difference between the identification of the
reservoir fill port center using the manufacturer's template and fluoroscopic
guidance was assessed on four consecutive refill procedures by a two physicians.
A distance surpassing that between the center and the margin of the port (3.5 mm)
was considered a clinically relevant deviation. Analyses were performed with a
one-sample t-test, with p < 0.05 indicating statistical significance. RESULTS:
The mean difference distance between identification markings of the target with
fluoroscopic guidance and with the template was 8.2 mm, with limited variance
(2.7 mm). For all individual refill procedures, the port center identification
accuracy differed significantly from zero (all p < 0.001) and from the clinically
relevant cut-off point of 3.5 mm (all p < 0.001). Only seven attempts (6.4%) were
within the margins of the fill port. CONCLUSIONS: Our results suggest poor
accuracy of insertion point identification using the template. This highlights
the potential risk of errors related to identification of the puncture site using
the template-guided technique.
PMID- 25117196
TI - Ceftobiprole medocaril: a review of its use in patients with hospital- or
community-acquired pneumonia.
AB - Ceftobiprole, the active metabolite of the prodrug ceftobiprole medocaril
(Zevtera((r))), is a new generation broad-spectrum intravenous cephalosporin with
activity against methicillin-resistant Staphylococcus aureus. Ceftobiprole
exhibits potent in vitro activity against a number of Gram-positive and Gram
negative pathogens associated with hospital-acquired pneumonia (HAP) and
community-acquired pneumonia (CAP). It is the first cephalosporin monotherapy
approved in the EU for the treatment of both HAP (excluding ventilator associated
pneumonia [VAP]) and CAP. In phase III trials, ceftobiprole medocaril was
noninferior, in terms of clinical cure rates at the test-of-cure visit, to
ceftazidime plus linezolid in patients with HAP and to ceftriaxone +/- linezolid
in patients with CAP severe enough to require hospitalization. In patients with
HAP, noninferiority of ceftobiprole medocaril to ceftazidime plus linezolid was
not demonstrated in a subset of patients with VAP. In patients with CAP,
ceftobiprole medocaril was effective in those at risk for poor outcomes
(pneumonia severity index >=91, Pneumonia Patient Outcomes Research Team score IV
V or bacteraemic pneumonia). In the phase III trials, ceftobiprole medocaril was
generally well tolerated, with ~10 % of patients discontinuing the treatment
because of adverse events. The most common treatment-related adverse events
occurring in ceftobiprole recipients in the trials in patients with HAP or CAP
included nausea, diarrhoea, infusion site reactions, vomiting, hepatic enzyme
elevations and hyponatraemia. Therefore, ceftobiprole medocaril monotherapy
offers a simplified option for the initial empirical treatment of patients with
HAP (excluding VAP) and in those with CAP requiring hospitalization.
PMID- 25117197
TI - Daclatasvir + asunaprevir: first global approval.
AB - The combination of daclatasvir + asunaprevir [Daklinza((r)) + Sunvepra((r))
(Japan)], two direct-acting antiviral agents, has been developed by Bristol-Myers
Squibb for the treatment of patients with chronic hepatitis C virus (HCV)
genotype 1 infections, including those with compensated cirrhosis. Daclatasvir +
asunaprevir has received its first global approval in this indication in Japan.
Daclatasvir + asunaprevir is the first all-oral, interferon- and ribavirin-free
regimen for this indication. This article summarizes the milestones in the
development of daclatasvir + asunaprevir leading to this first approval for the
treatment of chronic HCV genotype 1 infections.
PMID- 25117198
TI - Treatment of HCV infection with the novel NS3/4A protease inhibitors.
AB - HCV NS3/4A serine protease inhibitors are the first class of direct acting
antivirals (DAA) introduced in clinical practice. The first generation agents,
selective against HCV genotype 1, are used in association with pegylated
interferons and ribavirin allowing increased cure rates at the price of increased
toxicity, significant drug interactions and high risk of selecting mutants
conferring cross-resistance to the entire class. A large number of second-wave
HCV protease inhibitors are currently in clinical development. Advancements
include higher potency, activity against a wider number of genotypes, improved
tolerability, easier dosing schedules, although their genetic barrier to
resistance remains low, especially for subtype 1a, except for the most recent
grazoprevir and ACH-2684. The most relevant progress regards the combination with
other classes of DAA allowing construction of interferon-free regimens of short
duration, good tolerability with exceptionally high cure rates.
PMID- 25117200
TI - Cross-Cultural Considerations in Pediatric Neuropsychology: A Review and Call to
Attention.
AB - In the search to understand the basis of performance discrepancies, many
clinicians are recognizing that, often, factors with no direct relationship to
brain functioning influence performance on neuropsychological measures of
cognition among children and adolescents. The emergent research on cross-cultural
neuropsychology indicates that while the test performance discrepancies do indeed
exist, they can be explained by a number of other factors, some of which are
known and others that have yet to be operationalized or even identified. While a
review of all such factors is beyond the scope of this article, an examination of
those that have received the most attention is presented: factors associated with
the examinee, factors associated with the neuropsychological measures, cultural
competency of the examiner, and factors at the organizational/political level.
PMID- 25117201
TI - Factors that predict remission of infant atopic dermatitis: a systematic review.
AB - The individual prognosis of infants with atopic dermatitis (AD) is important for
parents, healthcare professionals, and society. The aim of this study was to
investigate predictors for remission of infant AD until school age. A systematic
review was carried out of clinical and epidemiological studies investigating the
effect of filaggrin gene (FLG) loss-of-function mutations, sex, exposure to pets,
topical anti-inflammatory treatment, disease severity, and atopic sensitization
during infancy on complete remission of infant-onset AD until 6-7 years of age.
Systematic electronic searches until September 2013, data abstraction, and study
quality assessment (Newcastle-Ottawa Scale) were performed. From 3,316 abstracts
identified, 2 studies of good study quality were included. Parental allergies and
sex did not significantly affect remission. For non-remission of AD, the included
articles reported an association with any atopic sensitization at 2 years old
(adjusted odds ratio [aOR] 2.76; 95% confidence interval (CI) 1.29-5.91),
frequent scratching with early AD (aOR 5.86; 95% CI 3.04-11.29), objective
severity score at 2 years old (aOR 1.10; 95% CI 1.07-1.14), and exposure to pets
(cat OR 2.33; 95% CI 0.85-6.38). It is largely unknown which factors predict
remission of infant AD. This is a highly relevant research gap that hinders
patient information on the prognosis of infant-onset AD.
PMID- 25117199
TI - Direct detection of biotinylated proteins by mass spectrometry.
AB - Mass spectrometric strategies to identify protein subpopulations involved in
specific biological functions rely on covalently tagging biotin to proteins using
various chemical modification methods. The biotin tag is primarily used for
enrichment of the targeted subpopulation for subsequent mass spectrometry (MS)
analysis. A limitation of these strategies is that MS analysis does not easily
discriminate unlabeled contaminants from the labeled protein subpopulation under
study. To solve this problem, we developed a flexible method that only relies on
direct MS detection of biotin-tagged proteins called "Direct Detection of Biotin
containing Tags" (DiDBiT). Compared with conventional targeted proteomic
strategies, DiDBiT improves direct detection of biotinylated proteins ~200 fold.
We show that DiDBiT is applicable to several protein labeling protocols in cell
culture and in vivo using cell permeable NHS-biotin and incorporation of the
noncanonical amino acid, azidohomoalanine (AHA), into newly synthesized proteins,
followed by click chemistry tagging with biotin. We demonstrate that DiDBiT
improves the direct detection of biotin-tagged newly synthesized peptides more
than 20-fold compared to conventional methods. With the increased sensitivity
afforded by DiDBiT, we demonstrate the MS detection of newly synthesized proteins
labeled in vivo in the rodent nervous system with unprecedented temporal
resolution as short as 3 h.
PMID- 25117204
TI - "Can we declare victory and move on?" The case against funding burden-of-disease
studies.
AB - Resources devoted to the development of burden-of-disease studies detract from
much needed cost-effectiveness and cost-benefit studies. Practitioners need to
help funders of burden-of-disease projects recognize the potential of all tools
of decision analysis and economic evaluation in improving the efficiency and
equity for the health care system.
PMID- 25117203
TI - Identification of a putative Tdp1 inhibitor (CD00509) by in vitro and cell-based
assays.
AB - Mutations of DNA repair pathways contribute to tumorigenesis and provide a
therapeutic target for synthetic lethal interactions in tumor cells. Given that
tyrosyl-DNA phosphodiesterase 1 (Tdp1) repairs stalled topoisomerase-I DNA
complexes, we hypothesized that inhibition of Tdp1 has synthetic lethal effects
in some cancers. To test this, we screened tumor arrays for Tdp1 expression and
observed that Tdp1 is expressed in many tumors, including more than 90% of human
breast tumors. Subsequent chemical screening identified putative Tdp1 inhibitors.
Treatment of control human mammary epithelial cells and the breast cancer cell
line MCF-7 with compound CD00509 preferentially sensitized MCF-7 cells to
camptothecin and decreased cell proliferation 25% more than camptothecin
treatment alone. This suggests that CD00509 specifically targeted Tdp1 in vitro,
and CD00509 increased the sensitivity of wild-type murine embryonic fibroblasts
(MEFs) to camptothecin to a degree comparable to that of Tdp1(-/-) MEFs. In
addition, consistent with poly ADP-ribose polymerase-1 (PARP-1) collaborating
with Tdp1 in DNA repair, combined Tdp1 and PARP-1 inhibition was more detrimental
to MCF-7 cells than either treatment alone, whereas the combination was not
additively harmful to control mammary cells. We conclude that targeting Tdp1 in
anticancer therapy preferentially enhances the sensitivity of some breast cancer
cells to camptothecin and may be an effective adjuvant for breast cancer therapy.
PMID- 25117205
TI - Hospital-based health technology assessment: insights from New Zealand.
PMID- 25117206
TI - Neuropsychological Assessment of Children With Reading Disabilities From 8 to 10
Years Old: An Exploratory Portuguese Study.
AB - Reading disabilities are one of the most significant causes of school failure and
may result from different causes and cognitive processes. A comprehensive battery
of neuropsychological tests was applied to a control group of 102 children (46
girls, 56 boys) with no history of learning disabilities and 32 children (13
girls, 19 boys) with poor reading achievement (PRA) to characterize their
cognitive profile. A principal component analysis of the cognitive measures was
undertaken to identify cognitive domains. Age-adjusted normative data were
computed from controls for verbal and visuospatial abilities, psychomotor skills,
executive functions, and a total score. Significant differences were found
between the 2 groups. Although single tests could not identify children with PRA,
measures of oral and written language, immediate and working memory, calculation,
and verbal learning discriminated the 2 groups. A logistic regression model using
these factors allowed us to identify 91.2% of healthy children and 96.9% of
children with PRA. PRA may result from different patterns of cognitive
difficulties, and it is more common in children with oral language and working
memory deficits. Wide-range cognitive testing is necessary to identify strong and
weak areas to plan personalized intervention programs.
PMID- 25117208
TI - Effect of positive airway pressure therapy on seizure control in patients with
epilepsy and obstructive sleep apnea.
AB - Previous studies suggest that treatment for obstructive sleep apnea (OSA) in
patients with epilepsy can improve seizure control. We investigated the effect of
positive airway pressure (PAP) therapy on seizures in adults with epilepsy
referred to the Cleveland Clinic for polysomnography (PSG) from 1997 to 2010.
Seizure outcome at baseline and 1 year later was compared in patients with no OSA
(apnea-hypopnea index [AHI] <5), patients with PAP-treated OSA, and patients with
untreated OSA. One hundred thirty-two subjects (age: 40.2+/-13 (18-76) years,
65.4% female) were included. Seventy-six (57.6%) subjects had OSA; of these, 43
(56.6%) were on PAP therapy, and 33 (43.4%) were not on PAP therapy (either PAP
intolerant or refused therapy). Of the group with PAP-treated OSA, 83.7% were
adherent (use >=4 h/night at least 5 nights/week). The percentage of subjects
with >=50% seizure reduction and the mean percentage of seizure reduction were
significantly greater in the group with PAP-treated OSA (73.9%; 58.5%) than in
subjects with untreated OSA (14.3%; 17.0%). There were significantly more
subjects with successful outcomes (with >=50% seizure reduction or seizure-free
at both baseline and follow-up) in the group with PAP-treated OSA (83.7%) than in
the groups with no OSA (53.6%) and untreated OSA (39.4%). After adjusting for
age, gender, body mass index, AHI, and epilepsy duration, we found that the odds
of successful outcomes in subjects in the group with PAP-treated OSA were 9.9 and
3.91 times those of the groups with untreated OSA and no OSA, respectively. The
group with PAP-treated OSA had 32.3 times the odds of having a >=50% seizure
reduction compared with the group with untreated OSA and 6.13 times compared with
the group with no OSA. Positive airway pressure therapy appears to produce
beneficial effects on seizures in adult patients with epilepsy and OSA.
PMID- 25117209
TI - Mycobacterium ulcerans disease (Buruli ulcer) in Mali: A new potential African
endemic country.
PMID- 25117207
TI - The neurosteroid 5beta-pregnan-3alpha-ol-20-one enhances actions of etomidate as
a positive allosteric modulator of alpha1beta2gamma2L GABAA receptors.
AB - BACKGROUND AND PURPOSE: Neurosteroids potentiate responses of the GABAA receptor
to the endogenous agonist GABA. Here, we examined the ability of neurosteroids to
potentiate responses to the allosteric activators etomidate, pentobarbital and
propofol. EXPERIMENTAL APPROACH: Electrophysiological assays were conducted on
rat alpha1beta2gamma2L GABAA receptors expressed in HEK 293 cells. The sedative
activity of etomidate was studied in Xenopus tadpoles and mice. Effects of
neurosteroids on etomidate-elicited inhibition of cortisol synthesis were
determined in human adrenocortical cells. KEY RESULTS: The neurosteroid 5beta
pregnan-3alpha-ol-20-one (3alpha5betaP) potentiated activation of GABAA receptors
by GABA and allosteric activators. Co-application of 1 MUM 3alpha5betaP induced a
leftward shift (almost 100-fold) of the whole-cell macroscopic concentration
response relationship for gating by etomidate. Co-application of 100 nM
3alpha5betaP reduced the EC50 for potentiation by etomidate of currents elicited
by 0.5 MUM GABA by about three-fold. In vivo, 3alpha5betaP (1mg kg(-1) ) reduced
the dose of etomidate required to produce loss of righting in mice (ED50 ) by
almost 10-fold. In tadpoles, the presence of 50 or 100 nM 3alpha5betaP shifted
the EC50 for loss of righting about three- or ten-fold respectively. Exposure to
3alpha5betaP did not influence inhibition of cortisol synthesis by etomidate.
CONCLUSIONS AND IMPLICATIONS: Potentiating neurosteroids act similarly on
orthosterically and allosterically activated GABAA receptors. Co-application of
neurosteroids with etomidate can significantly reduce dosage requirements for the
anaesthetic, and is a potentially beneficial combination to reduce undesired side
effects.
PMID- 25117212
TI - Bacteria aerosol spread and wound bacteria reduction with different methods for
wound debridement in an animal model.
AB - Debridement is essential in wound treatment to remove necrotic tissue and wound
bacteria but may lead to bacteria spread by aerosolization. This study
investigated the wound bacterial reduction and bacterial transmission induced by
debridement using curette, plasma-mediated bipolar radiofrequency ablation
(Coblation(r)) or hydrodebridement (Versajet(r)). Full thickness dermal wounds in
porcine joint specimens inoculated with S. aureus were debrided with curette,
Coblation, Versajet, or were left untreated. During and after debridement,
aerosolized bacteria were measured and to assess wound bacterial load,
quantitative swab samples were taken from each wound. Only Coblation was able to
reduce the bacterial load of the wound significantly. Versajet debridement
resulted in a significant bacterial aerosolization, but this was not the case
with Coblation and curette debridement. This study shows that Coblation is a
promising wound debridement method, which effectively reduces the wound bed
bacterial load without the risk of bacterial aerosolization.
PMID- 25117216
TI - Spectrum of Mathematical Weaknesses: Related Neuropsychological Correlates.
AB - Math disorders have been recognized for as long as language disorders yet have
received far less research. Mathematics is a complex construct and its
development may be dependent on multiple cognitive abilities. Several studies
have shown that short-term memory, working memory, visuospatial skills,
processing speed, and various language skills relate to and may facilitate math
development and performance. The hypotheses explored in this research were that
children who performed worse on math achievement than on Full-Scale IQ would
exhibit weaknesses in executive functions, memory, and visuoperceptual skills.
Participants included 436 children (27% girls, 73% boys; age range = 5-17 years,
M(age) = 9.45 years) who were referred for neuropsychological evaluations due to
academic and/or behavioral problems. This article specifically focuses on the
spectrum of math weakness rather than clinical disability, which has yet to be
investigated in the literature. Results suggest that children with relative
weakness to impairments in math were significantly more likely to have cognitive
weaknesses to impairments on neuropsychological variables, as compared with
children without math weaknesses. Specifically, the math-weak children exhibit a
weakness to impairment on measures involving attention, language, visuoperceptual
skills, memory, reading, and spelling. Overall, our results suggest that math
development is multifaceted.
PMID- 25117210
TI - Left ventricular hypertrophy and obesity: only a matter of fat?
AB - Obesity can be regarded as an energy balance disorder in which inappropriate
expansion and dys-function of adipose tissue lead to unfavorable outcomes. Even
in the absence of hypertension, adiposity induces structural and functional
changes in the heart through hemodynamic and non hemodynamic factors. In the
"obese" heart, besides the growth of cardiomyocytes, interstitial fat
infiltration and triglyceride accumulation in the contractile elements
importantly contribute to left-ventricular mass (LVM) accrual, hypertrophy (LVH)
and geometric pattern. In harmony with this, the likelihood of LVH is greater in
either obese normotensive or hypertensive individuals than in their non-obese
counterparts. Interestingly, recent observations highlight the increasing
prevalence of the "concentric" (ie, combined remodeling and hypertrophy), rather
than "eccentric" pattern of LV geometry in obesity. Nonetheless, obesity is
linked with lack of decrease, or even increase, of LVM over time, independently
of blood pressure control and hypertensive treatment. Although obesity-related LV
changes result in progressive systolic and diastolic heart failure, the
assessment of LVM and LVH in obese individuals still remains a difficult task. In
this scenario, it is tempting to speculate that therapeutic interventions for
reversal of LVH in obesity should either overcome the "non-hemodynamic" factors
or reduce the hemodynamic load. Indeed, weight loss, either achieved by lifestyle
changes or bariatric procedures, decreases LVM and improves LV function
regardless of blood pressure status. These and other mechanistic insights are
discussed in this review, which focuses on "adipose dysfunction" as potential
instigator of, and putative therapeutic target for, LVH regression in the setting
of obesity.
PMID- 25117217
TI - ELISPOT Techniques.
AB - The enzyme-linked immunospot (ELISPOT) assay is a widely used method for
enumerating antigen-specific cytokine-producing or antibody-secreting immune
cells. It is one of the most effective immunological and diagnostic approaches to
detect and quantify low-frequency cytokine- or antibody-producing cells in human
and animal tissues, such as peripheral blood, lymph nodes, and spleen. Detection
and quantification of specific cytokine-producing cells by the ELISPOT assay is
based on the formation of visible spots at the site of cytokine release by the
cells under investigation (e.g., T cells) using pairs of different capture and
detection antibodies under optimized conditions.Here we focus mainly on
practical, optimized protocols for cytokine ELISPOT assays for detection of mouse
and human cytokine-producing immune cells (e.g., peripheral blood mononuclear
cells, PBMC), including suggestions for trouble-shooting and optimizing steps for
problematic tissue samples.
PMID- 25117211
TI - Neuroprotective effects of the anti-cancer drug sunitinib in models of HIV
neurotoxicity suggests potential for the treatment of neurodegenerative
disorders.
AB - BACKGROUND AND PURPOSE: Anti-retrovirals have improved and extended the life
expectancy of patients with HIV. However, as this population ages, the prevalence
of cognitive changes is increasing. Aberrant activation of kinases, such as
receptor tyrosine kinases (RTKs) and cyclin-dependent kinase 5 (CDK5), play a
role in the mechanisms of HIV neurotoxicity. Inhibitors of CDK5, such as
roscovitine, have neuroprotective effects; however, CNS penetration is low.
Interestingly, tyrosine kinase inhibitors (TKIs) display some CDK inhibitory
activity and ability to cross the blood-brain barrier. EXPERIMENTAL APPROACH: We
screened a small group of known TKIs for a candidate with additional CDK5
inhibitory activity and tested the efficacy of the candidate in in vitro and in
vivo models of HIV-gp120 neurotoxicity. KEY RESULTS: Among 12 different
compounds, sunitinib inhibited CDK5 with an IC50 of 4.2 MUM. In silico analysis
revealed that, similarly to roscovitine, sunitinib fitted 6 of 10 features of the
CDK5 pharmacophore. In a cell-based model, sunitinib reduced CDK5 phosphorylation
(pCDK5), calpain-dependent p35/p25 conversion and protected neuronal cells from
the toxic effects of gp120. In glial fibrillary acidic protein-gp120 transgenic
(tg) mice, sunitinib reduced levels of pCDK5, p35/p25 and phosphorylated tau
protein, along with amelioration of the neurodegenerative pathology. CONCLUSIONS
AND IMPLICATIONS: Compounds such as sunitinib with dual kinase inhibitory
activity could ameliorate the cognitive impairment associated with chronic HIV
infection of the CNS. Moreover, repositioning existing low MW compounds holds
promise for the treatment of patients with neurodegenerative disorders.
PMID- 25117219
TI - A comparison of the degree of effort involved in the TOMM and the ACS Word Choice
Test using a dual-task paradigm.
AB - The aims of the current study were to: (a) examine the predictive validity and
efficacy of the Advanced Clinical Solutions Word Choice Test (WCT) as a measure
of effort relative to the Test of Memory Malingering (TOMM); (b) investigate
whether performing a dual (distraction) task would undermine performance on
either test; (c) assess the effect of coaching on the diagnostic accuracy of both
the WCT and the TOMM; and (d) establish an optimal cut score for the WCT. The
current study used a simulation design based on an analogue design in which
normal participants were instructed to either apply full effort or simulate a
brain injury on the tasks without being detected. Participants included 93
undergraduate university students who were randomly assigned to 1 of 4
conditions: (a) distraction, (b) uncoached traumatic brain injury (TBI)
simulators, (c) coached TBI simulators, or (d) full effort. The results
demonstrated that the WCT and the TOMM were effective in detecting simulated
cognitive impairment. Both tests were resistant to the effects of distraction and
were equally effective in detecting coached and uncoached simulators. A cut score
of 42 on the WCT was found to provide optimal specificity and sensitivity on the
test.
PMID- 25117220
TI - History of plant lectin research.
AB - Numerous plant species are known to express one or more lectins or proteins
containing a lectin domain, enabling these proteins to select and bind specific
carbohydrate structures. The group of plant lectins is quite heterogeneous since
lectins differ in their molecular structure, specificity for certain carbohydrate
structures, and biological activities resulting therefrom. This chapter presents
a short historical overview on how plant lectin research has evolved over the
years from a discipline aiming merely at the purification and characterization of
plant lectins towards the application of plant lectins as tools in glycobiology.
PMID- 25117221
TI - Fungal lectins: a growing family.
AB - Fungi are members of a large group of eukaryotic organisms that include yeasts
and molds, as well as the most familiar member, mushrooms. Fungal lectins with
unique specificity and structures have been discovered. In general, fungal
lectins are classified into specific families based on their amino acid sequences
and three-dimensional structures. In this chapter, we provide an overview of the
approximately 80 types of mushroom and fungal lectins that have been isolated and
studied to date. In particular, we have focused on ten fungal lectins (Agaricus
bisporus, Agrocybe cylindracea, Aleuria aurantia, Aspergillus oryzae, Clitocybe
nebularis, Marasmius oreades, Psathyrella velutina, Rhizopus stolonifer, Pholiota
squarrosa, Polyporus squamosus), many of which are commercially available and
their properties, sugar-binding specificities, structural grouping into families,
and applications for biological research being described. The sialic acid
specific lectins (Agrocybe cylindracea and Polyporus squamosus) and fucose
specific lectins (Aleuria aurantia, Aspergillus oryzae, Rhizopus stolonifer, and
Pholiota squarrosa) each showed potential for use in identifying sialic acid
glycoconjugates and fucose glycoconjugates. Although not much is currently known
about fungal lectins compared to animal and plant lectins, the knowledge
accumulated thus far shows great promise for several applications in the fields
of taxonomy, biomedicine, and molecular and cellular biology.
PMID- 25117223
TI - Hemagglutination (inhibition) assay.
AB - The hemagglutination assay is a simple and easy method to obtain semi
quantitative data on the sugar binding and specificity of a lectin. An active
lectin agglutinates erythrocytes by recognizing a carbohydrate on the cell
surface and forming a cross-linked network in suspension. By serially diluting
the lectin in a 96-well microtiter plate and adding a constant quantity of
erythrocytes, the lectin activity can be estimated.
PMID- 25117218
TI - IL-1beta and IL-18: inflammatory markers or mediators of hypertension?
AB - Chronic inflammation in the kidneys and vascular wall is a major contributor to
hypertension. However, the stimuli and cellular mechanisms responsible for such
inflammatory responses remain poorly defined. Inflammasomes are crucial
initiators of sterile inflammation in other diseases such as rheumatoid arthritis
and gout. These pattern recognition receptors detect host-derived danger
associated molecular patterns (DAMPs), such as microcrystals and reactive oxygen
species, and respond by inducing activation of caspase-1. Caspase-1 then
processes the cytokines pro-IL-1beta and pro-IL-18 into their active forms thus
triggering inflammation. While IL-1beta and IL-18 are known to be elevated in
hypertensive patients, no studies have examined whether this occurs downstream of
inflammasome activation or whether inhibition of inflammasome and/or IL-1beta/IL
18 signalling prevents hypertension. In this review, we will discuss some known
actions of IL-1beta and IL-18 on leukocyte and vessel wall function that could
potentially underlie a prohypertensive role for these cytokines. We will describe
the major classes of inflammasome-activating DAMPs and present evidence that at
least some of these are elevated in the setting of hypertension. Finally, we will
provide information on drugs that are currently used to inhibit inflammasome/IL
1beta/IL-18 signalling and how these might ultimately be used as therapeutic
agents for the clinical management of hypertension.
PMID- 25117222
TI - The "white kidney bean incident" in Japan.
AB - Lectin poisoning occurred in Japan in 2006 after a TV broadcast that introduced a
new diet of eating staple foods with powdered toasted white kidney beans, seeds
of Phaseolus vulgaris. Although the method is based on the action of a heat
stable alpha-amylase inhibitor in the beans, phaseolamin, more than 1,000 viewers
who tried the method suffered from acute intestinal symptoms and 100 people were
hospitalized. Lectins in the white kidney beans were suspected to be the cause of
the trouble. We were asked to investigate the lectin activity remaining in the
beans after the heat treatment recommended on the TV program. The test suggested
that the heat treatment was insufficient to inactivate the lectin activity,
which, combined with our ignorance of carbohydrate signaling in the intestine,
was the cause of the problem.
PMID- 25117224
TI - Preparation of affinity adsorbents and purification of lectins from natural
sources.
AB - Lectins are purified by affinity chromatography to take advantage of their
carbohydrate-specific interactions. Highly efficient affinity adsorbents are
powerful tools to obtain homogeneous lectins with distinct specificities. Here,
we describe three methods to prepare affinity adsorbents by immobilizing
carbohydrates or glycoconjugates on agarose gel beads. Because the ligands are
immobilized via a stable and nonionic linkage under mild conditions, the
adsorbents possess high binding capacity for lectins with low nonspecific
adsorption and can withstand repeated use. The procedures require neither
specialized techniques and apparatus nor highly toxic compounds. Using these
adsorbents, many plant and animal lectins can be purified in a few steps.
PMID- 25117225
TI - High-performance lectin affinity chromatography.
AB - Lectin high-performance liquid chromatography techniques have contributed to the
growing interest in glycoproteomics. Affinity chromatography is a very effective
method to separate and purify trace amount of biological substances. In this
chapter, we describe a basic procedure for separation of glycoproteins using
commercially available lectin-HPLC columns. As an example, alpha-fetoprotein,
known as a biomarker of liver cancer, can be separated at the level of their
glyco-isomers by using a Lens culinaris agglutinin (LCA) column.
PMID- 25117226
TI - Determination of glycan motifs using serial lectin affinity chromatography.
AB - Serial lectin affinity chromatography is a convenient technique for
characterizing glycan motifs (terminal glycan structures) of glycoproteins or
released glycans. When these glycoconjugates are applied serially or in parallel
to lectin-immobilized columns, information regarding the glycan motifs can be
obtained. We demonstrate lectin affinity chromatographic methods for determining
O-linked glycan structures of MUC1 purified from a breast cancer cell line, YMB
S, N-linked glycan structures of serum prostate-specific antigen from prostate
cancer, and serum alkaline phosphatases from choriocarcinoma. These lectin
fractionated samples are analyzed quantitatively by measuring radioactivity,
antigen contents are analyzed using enzyme-linked immunosorbent assay, and
enzymatic activities are assessed.
PMID- 25117227
TI - Lectin-probed western blot analysis.
AB - Lectin-probed western blot analysis, the so-called lectin blot analysis, is a
useful method to yield basic information on the glycan structures of
glycoproteins, based on the carbohydrate-binding specificities of lectins. By
lectin blot analysis, researchers can directly analyze the glycan structures
without releasing the glycans from glycoproteins. Here, the author describes
protocols for standard analysis, and applies analysis in combination with
glycosidase digestion of blot.
PMID- 25117228
TI - Solid-phase assay of lectin activity using HRP-conjugated glycoproteins.
AB - Various enzyme-conjugated probes have been widely used for detection of specific
interactions between biomolecules. In the case of glycan-protein interaction,
horseradish peroxidase (HRP)-conjugated glycoproteins (HRP-GPs) are useful for
the detection of carbohydrate-binding activity of plant and animal lectins. In
this chapter, a typical solid-phase assay of the carbohydrate-binding activity of
Sophora japonica agglutinin I, a Gal/GalNAc-specific lectin, using HRP-conjugated
asialofetuin is described. HRP-GPs are versatile tools for probing lectin
activities in crude extracts, screening many samples at one time, and applicable
not only for solid-phase binding assays but also samples which are dot- or
Western-blotted onto the membrane.
PMID- 25117229
TI - A simple viral neuraminidase-based detection for high-throughput screening of
viral hemagglutinin-host receptor specificity.
AB - The correlation between precise interactions of influenza A virus hemagglutinins
with host cell surface glycans having terminal sialic acids and host range
specificity has provoked the development of a high-throughput viral-receptor
specificity assay. Here, we describe the use of the virus itself as a specific
antibody coupled to enzymes (virus with neuraminidase spikes) for determining its
binding specificity to glycans, a strategy that reduces not only the cost but
also the tedious steps of adding primary and secondary antibodies and washing
between each step. All of the steps, including coating the glycopolymers onto
microtiter plates, virus binding, and visual and quantitative detection of
fluorescence products that correlate well with the amount of glycan-bound
viruses, can be done within 3 h. This simple, rapid, sensitive, and reliable
strategy is an ideal method for detection of high-throughput influenza virus
receptor-binding preference not only for studies on viral evolution and
transmission but also for viral surveillance in pandemic preparedness, leading to
efficient prevention and control of the disease.
PMID- 25117230
TI - Lectin affinity electrophoresis.
AB - An interaction or a binding event typically changes the electrophoretic
properties of a molecule. Affinity electrophoresis methods detect changes in the
electrophoretic pattern of molecules (mainly macromolecules) that occur as a
result of biospecific interactions or complex formation. Lectin affinity
electrophoresis is a very effective method for the detection and analysis of
trace amounts of glycobiological substances. It is particularly useful for
isolating and separating the glycoisomers of target molecules. Here, we describe
a sensitive technique for the detection of glycoproteins separated by agarose gel
lectin affinity electrophoresis that uses antibody-affinity blotting. The
technique is tested using alpha-fetoprotein with lectin (Lens culinaris
agglutinin and Phaseolus vulgaris agglutinin)-agarose gels.
PMID- 25117231
TI - Capillary-based lectin affinity electrophoresis for interaction analysis between
lectins and glycans.
AB - Capillary affinity electrophoresis (CAE) is a powerful technique for glycan
analysis, and one of the analytical approaches for analyzing the interaction
between lectins and glycans. The method is based on the high-resolution
separation of fluorescently labeled glycans by capillary electrophoresis (CE)
with laser-induced fluorescence detection (LIF) in the presence of lectins (or
glycan binding proteins). CAE allows simultaneous determination of glycan
structures in a complex mixture of glycans. In addition, we can calculate the
binding kinetics on a specific glycan in the complex mixture of glycans with a
lectin. Here, we show detailed procedures for capillary affinity electrophoresis
of fluorescently labeled glycans with lectins using CE-LIF apparatus. Its
application to screening a sialic acid binding protein in plant barks is also
shown.
PMID- 25117232
TI - Basic procedures for lectin flow cytometry.
AB - Glycans located on the cell surface regulate cell-cell interaction, cell homing,
and signal transmission, which are particularly important for communication among
cells. Certain cell types contain unique cell surface glycan structures, which
have been utilized as markers for characterization. Flow cytometry is a powerful
technology that enables the examination of multiple parameters of individual
cells (e.g., cell size, internal complexity, and surface marker expression
level). In this chapter, we describe a step-by-step procedure on how to detect
glycans on the cell surface of live cells by flow cytometer, using lectins.
PMID- 25117233
TI - Histochemical staining using lectin probes.
AB - In histochemistry and cytochemistry, lectins are often used as probes for the
localization of carbohydrates in cells and tissues. With lectins, cells and
tissues can be identified as a particular type or a group in situ. Various
lectins have been used for mapping of normal cells and tissues, pathological
diagnosis such as malignant transformation, and identification of cell lineages
during development. This chapter describes light and electron microscopic methods
using lectin probes for determining carbohydrate localization in cells and
tissues.
PMID- 25117234
TI - Equilibrium dialysis using chromophoric sugar derivatives.
AB - Equilibrium dialysis has been used to examine the binding affinity of ligands to
proteins. It is a simple and reliable method, which requires only inexpensive
equipment. For analysis of lectin-sugar interactions, the lectin and sugar are
placed in the individual chambers separated by the membrane to allow the sugar to
diffuse into the lectin chamber. After equilibrium has been reached, the
concentrations of the sugar in both chambers are determined to evaluate the sugar
binding affinity of lectin. In this chapter, an example of the equilibrium
dialysis experiment using the chromophoric derivatives of galactose and N
acetylgalactosamine is demonstrated, which reveals the difference in the affinity
as well as specificities of two different carbohydrate-binding sites present in
the B-chains of the plant lectin ricin.
PMID- 25117235
TI - Centrifugal ultrafiltration-HPLC method for interaction analysis between lectins
and sugars.
AB - The centrifugal ultrafiltration-HPLC method is a simple and rapid method for
analyzing the binding interaction between lectins and sugars (oligosaccharides).
In this method, a lectin is mixed with a fluorescent-labeled oligosaccharide in
buffer and the unbound oligosaccharide recovered by centrifugal ultrafiltration
is isolated and quantified by high-performance liquid chromatography. The binding
activity is defined as a ratio (percentage) of the amount of bound
oligosaccharide to that added, where the former is obtained by subtracting the
amount of unbound oligosaccharide from the latter. The oligosaccharide-binding
specificity of a lectin can be determined by comparing the binding activities
with a variety of fluorescent-labeled oligosaccharides. The association constant
and the optimum pH and temperature of the binding interaction between lectins and
fluorescent-labeled oligosaccharides can be easily analyzed by this method.
PMID- 25117236
TI - Surface plasmon resonance as a tool to characterize lectin-carbohydrate
interactions.
AB - Biosensors based on surface plasmon resonance (SPR) monitor changes in refractive
index in the vicinity of a surface in a real-time manner, which allows rapid,
label-free characterization of the interactions of various types of molecules,
from quantitative measurements of binding kinetics, thermodynamics, and
concentrations in complex samples to epitope analysis. This method is usually
capable of analyzing affinities in the range of millimolar to picomolar and is
sensitive (typically, the concentration range of the analyte is 0.1-100*Kd and
the typical volumes needed are in the range of 50-150 MUL). There are two major
applications of SPR biosensors for the analysis of lectin-carbohydrate
interactions: detailed characterization of the interaction (e.g., specificity,
affinity, kinetics, stoichiometry) and screening of lectin and
carbohydrate/glycoconjugate interactions for diagnosis, identification of
endogenous ligands, or binding properties of interest. Care should be taken,
since the interaction of lectin and carbohydrate on the solid phase is
complicated by the nonhomogeneous conditions under which binding occurs. However,
this may in fact mimic some biological conditions, such as those occurring in
cell-cell interactions.
PMID- 25117237
TI - Isothermal calorimetric analysis of lectin-sugar interaction.
AB - Isothermal titration calorimetry (ITC) is a powerful tool for analyzing lectin
glycan interactions because it can measure the binding affinity and thermodynamic
properties such as ?H and DeltaS in a single experiment without any chemical
modification or immobilization. Here we describe a method for preparing glycan
and lectin solution to minimize the buffer mismatch, setting parameters, and
performing experiments.
PMID- 25117238
TI - Carbohydrate-lectin interaction assay by fluorescence correlation spectroscopy
using fluorescence-labeled glycosylasparagines.
AB - Fluorescence correlation spectroscopy (FCS) is a high-throughput system for the
assay of interactions in solution and can be used to measure the numbers of
molecules and molecular size in micro-regions. FCS can be used to measure
interactions in environments that are close to those in vivo. It is a useful
technique for measuring bioactive substances, screening inhibitors, and detecting
the binding of materials, as well as for determining K d and IC50 values.
Glycosyl amino acids with natural oligosaccharides are useful for the interaction
assay of oligosaccharides. Fluorescence probes can be introduced into the
glycosyl amino acid while the whole structure of the oligosaccharide is
maintained. Carbohydrate-lectin interaction in a solution assay system can be
analyzed easily by FCS using fluorescence-labeled glycosylasparagine.
PMID- 25117239
TI - Lectin-based glycomics: how and when was the technology born?
AB - Lectin-based glycomics is an emerging, comprehensive technology in the post
genome sciences. The technique utilizes a panel of lectins, which is a group of
biomolecules capable of deciphering "glycocodes," with a novel platform
represented by a lectin microarray. The method enables multiple glycan-lectin
interaction analyses to be made so that differential glycan profiling can be
performed in a rapid and sensitive manner. This approach is in clear contrast to
another advanced technology, mass spectrometry, which requires prior glycan
liberation. Although the lectin microarray cannot provide definitive structures
of carbohydrates and their attachment sites, it gives useful clues concerning the
characteristic features of glycoconjugates. These include differences not only in
terminal modifications (e.g., sialic acid (Sia) linkage, types of fucosylation)
but also in higher ordered structures in terms of glycan density, depth, and
direction composed for both N- and O-glycans. However, before this technique
began to be implemented in earnest, many other low-throughput methods were
utilized in the late twentieth century. In this chapter, the author describes how
the current lectin microarray technique has developed based on his personal
experience.
PMID- 25117240
TI - Frontal affinity chromatography (FAC): theory and basic aspects.
AB - Frontal affinity chromatography (FAC) is a versatile analytical tool for
determining specific interactions between biomolecules and is particularly useful
in the field of glycobiology. This article presents its basic aspects, merits,
and theory.
PMID- 25117241
TI - Frontal affinity chromatography: practice of weak interaction analysis between
lectins and fluorescently labeled oligosaccharides.
AB - Frontal affinity chromatography (FAC) is a simple and effective method that is
applicable to the analysis of interactions between glycans and glycan-recognition
proteins, including lectins, with weak affinity ranging from 10(-4) to 10(-6) (M)
in terms of dissociation constant (Kd). Using conventional instruments, such as a
high-performance liquid chromatography (HPLC) system equipped with pump,
injector, (fluorescent) detector, and data recorder, the dissociation constants
for weak glycan-based interactions can be easily determined with high throughput
and accuracy. Notably, if the glycans are labeled with fluorescent dyes, only a
small amount of glycans is required for the analysis. Fluorescent labeling of
glycans is a common technique, and an increasing number of fluorescent-labeled
glycans are commercially available. In this chapter, an advanced FAC method using
fluorescent-labeled glycans is described.
PMID- 25117242
TI - Differential glycan analysis of an endogenous glycoprotein: toward clinical
implementation--from sample pretreatment to data standardization.
AB - There are huge numbers of clinical specimens being stored that contain potential
diagnostic marker molecules buried by the coexistence of high-abundance proteins.
To utilize such valuable stocks efficiently, we must develop appropriate
techniques to verify the molecules. Glycoproteins with disease-related
glycosylation changes are a group of useful molecules that have long been
recognized, but their application is not fully implemented. The technology for
comparative analysis of such glycoproteins in biological specimens has tended to
be left behind, which often leads to loss of useful information without it being
recognized. In this chapter, we feature antibody-assisted lectin profiling
employing antibody-overlay lectin microarray, the most suitable technology for
comparative glycoanalysis of a trace amount of glycoproteins contained in
biological specimens. We believe that sharing this detailed protocol will
accelerate the glycoproteomics-based discovery of glyco-biomarkers that has
attracted recent attention; simultaneously, it will increase the value of
clinical specimens as a gold mine of information that has yet to be exploited.
PMID- 25117243
TI - Lectin-microarray technique for glycomic profiling of fungal cell surfaces.
AB - Lectin microarrays are rows of lectins with different carbohydrate-binding
specificities spotted on surfaces of glass slides. Lectin microarray technique
enables glycomic analyses of carbohydrate composition of fungal cell walls. We
will describe an application of the technique in analyzing cell surface glycome
of yeast-form fungal cells in the living state. The analysis reveals genus- and
species-dependent complex cell surface carbohydrate structures of fungi, and
enabled us, therefore, to suggest that cell walls of yeast cells, which have been
considered to have relatively simple structures, actually have a more complex
structure containing galactose and fucose. This shows that the technique can be
used to find new insights into the study of phylogenetic relations and into the
classification of cells in the fungal kingdom based on cell wall glycome.
PMID- 25117244
TI - Application of lectin microarray to bacteria including Lactobacillus
casei/paracasei strains.
AB - Since 2005, lectin microarray technology has emerged as a simple and powerful
technique for comprehensive glycan analysis. By using evanescent-field
fluorescence detection technique, it has been applied for analysis of not only
glycoproteins and glycolipids secreted by eukaryotic cells but also
glycoconjugates on the cell surface of live eukaryotic cells. Bacterial cells are
known to be decorated with polysaccharides, teichoic acids, and proteins in the
peptide glycans of their cell wall and lipoteichoic acids in their phospholipid
bilayer. Specific glycan structures are characteristic of many highly pathogenic
bacteria, while polysaccharides moiety of lactic acid bacteria are known to play
a role as probiotics to modulate the host immune response. However, the method of
analysis and knowledge of glycosylation structure of bacteria are limited. Here,
we describe the development of a simple and sensitive method based on lectin
microarray technology for direct analysis of intact bacterial cell surface
glycomes. The method involves labeling bacterial cells with SYTOX Orange before
incubation with the lectin microarray. After washing, bound cells are directly
detected using an evanescent-field fluorescence scanner in a liquid phase. The
entire procedure takes 3 h from putting labeled bacteria on the microarray to
profiling its lectin binding affinity. Using this method, we compared the cell
surface glycomes from 16 different strains of L. casei/paracasei. The lectin
binding profile of most strains was found to be unique. Our technique provides a
novel strategy for rapid profiling of bacteria and enables us to differentiate
numerous bacterial strains with relevance to the biological functions of surface
glycosylation.
PMID- 25117245
TI - Live-cell imaging of human pluripotent stem cells by a novel lectin probe
rBC2LCN.
AB - We performed comprehensive glycome analysis of a large set of human pluripotent
stem cells (hPSCs) using a high-density lectin microarray. We found that a
recombinant lectin, rBC2LCN, binds exclusively to all of the undifferentiated
hPSCs tested, but not to differentiated somatic cells. rBC2LCN can be used for
both the staining and sorting of fixed and live hPSCs. rBC2LCN could serve as a
novel detection reagent for hPSCs, particularly given that rBC2LCN is cost
effective and, unlike conventional antibodies which require mammalian cells for
their production, is easy to produce in a large amount (0.1 g/L) in an
Escherichia coli expression system. Here we describe protocols for the
fluorescence staining of fixed and live hPSCs and their detection by flow
cytometry.
PMID- 25117246
TI - Carbohydrate-binding specificity of lectins using multiplexed glyco-bead array.
AB - Multiplexed bead array is an application that allows us to quantify multiple
ligands simultaneously by using flow cytometry. Glycopeptides are immobilized on
multiplexed beads, and the glycan-binding specificities of several lectins are
determined. This strategy is easy, rapid, and suitable for small amount of
samples, and allows the reliable elucidation under the identical condition. Such
a technology is useful for analyzing characteristics and functions of lectins.
PMID- 25117247
TI - Supported molecular matrix electrophoresis: a new membrane electrophoresis for
characterizing glycoproteins.
AB - Protein blotting is often used for identification and characterization of
proteins on a membrane to which proteins separated by gel electrophoresis are
transferred. The transferring process is sometimes problematic, in particular,
for mucins and proteoglycans. Here, we describe a novel membrane electrophoresis
technique, termed supported molecular matrix electrophoresis (SMME), in which a
porous polyvinylidene difluoride (PVDF) membrane filter is used as the separation
support. Proteins separated by this method can be immunoblotted without any
transferring procedures.
PMID- 25117248
TI - Overall strategy for functional analysis of animal lectins.
AB - Animal lectins elicit biological functions through the interaction with glycan
ligands. To clarify the functions of the lectins, both identification of their
glycan ligand structure and assessment of impact of lectin-glycan interaction on
the biological event are essential strategies. This chapter focuses on two of key
useful methodologies for planning experiments based on the strategies. One is the
detection of lectin-glycan interaction by the multivalent display of lectins and
glycans. This methodology is a powerful means for identification of the glycan
ligand structure and proteins and/or lipids carrying the glycan ligands for
lectins. The other is the intervention of lectin-glycan interaction to assess the
biological roles of lectins. Bioinformatics especially useful for animal lectins
will be also described in this chapter. The concepts described in this chapter
are versatile and applicable to a wide range of animal lectin research.
PMID- 25117249
TI - Evaluation of glycan-binding specificity by glycoconjugate microarray with an
evanescent-field fluorescence detection system.
AB - The glycan microarray is now an essential tool used to study lectins. With this
technique, glycan-binding specificity can be easily assessed by incubation with
an array immobilizing a series of glycans. Glycan microarrays have been developed
by numerous research groups around the world. Among the available microarrays,
our glycan microarray has two unique characteristics: one is the incorporation of
an evanescent-field fluorescence detection system and the other is the use of
multivalent glycopolymers. These two unique properties allow the highly sensitive
detection of only nanogram quantities of lectins even in crude samples such as
cell lysates and cell culture media. Thus, this system is suitable for the
initial screening of lectins, lectin-like molecules, lectin candidates, and
lectin mutants. Here I describe the protocols employed to analyze the glycan
binding specificity of lectins using our glycan microarray system.
PMID- 25117250
TI - Potential usage for in vivo lectin screening in live animals utilizing cell
surface mimetic glyco-nanoparticles, phosphorylcholine-coated quantum dots (PC
QDs).
AB - Utilizing glycosylated derivatives as a tag, we are able to explore novel counter
receptor of endogenous lectins or lectin-like molecules in vivo. We have
established the standardized methodology including preparation of glycosylated
derivatives and construction of a platform for tracing the molecules in vivo at
first. Combined use of an aminooxy-terminated thiol derivative and a
phosphorylcholine (PC) derivative provides quantum dots (QDs) with novel
functions for the chemical ligation of ketone-functionalized compounds and the
prevention of nonspecific protein adsorption concurrently. In order to track the
derivatives in vivo, near-infrared (NIR) fluorescence imaging of QDs displaying
various simple sugars (glyco-PC-QDs) after administration into the tail vein of
the mouse can be performed. It has revealed that distinct long-term
delocalization over 2 h can be observed depending on the species of glycans
ligated to PC-QDs at least in the liver. Until today we have performed live
animal imaging utilizing various kinds of sialyl glyco-PC-QDs. They are still
retained stably in whole body after 2 h while they showed significantly different
in vivo dynamics in the tissue distribution, suggesting that structure/sequence
of the neighboring sugar residues in the individual sialyl oligosaccharides might
influence the final organ-specific distribution, which should be equivalent to
the distribution of sialic acid-recognizing lectins. Here we describe a
standardized protocol using ligand-displayed PC-QDs for live cell/animal imaging
by versatile NIR fluorescence photometry without influence of size-dependent
accumulation/excretion pathway for nanoparticles (e.g., viruses)>10 nm in
hydrodynamic diameter by the liver.
PMID- 25117251
TI - Remodeling cell surface glycans using glycosylation inhibitors.
AB - Cell surface glycan remodeling is a useful method to modulate glycan-lectin
interactions. In this chapter, a facile and reliable method to remodel mammalian
cell surface N-glycans using inhibitors for N-glycan-processing enzymes is
described. The method is widely applicable to many mammalian systems because
those inhibitors work for the conserved glycosylation pathways among species.
PMID- 25117252
TI - Remodeling of glycans using glycosyltransferase genes.
AB - Remodeling of glycans on the cell surface is an essential technique to analyze
cellular function of lectin-glycan ligand interaction. Here we describe the
methods to identify the responsible enzyme (glycosyltransferase) regulating the
expression of the glycan of interest and to modulate the glycan expression by
overexpressing the glycosyltransferase gene. For the identification of the
responsible enzyme, we introduce a new method, CIRES (correlation index-based
responsible-enzyme gene screening), that consists of statistical comparison of
glycan expression profile obtained by flow cytometry and gene expression profile
obtained by DNA microarray.
PMID- 25117253
TI - Functional assay using lectin gene targeting technologies (over-expression).
AB - Function of lectin depends on its amino acid sequence of carbohydrate-recognition
domain (CRD), conformation, and extracellular/intracellular localization.
Altering lectin gene expression by over-expression or knockdown is a powerful
tool for analyzing its cellular function. Here, we describe a method of lectin
gene over-expression, taking a C-type lectin, mannan-binding protein (MBP), as an
example. Carbohydrate-binding ability of MBP, its subcellular localization, and
functional co-localization with ligand glycoprotein are assayed comparing with an
inactive mutant MBP.
PMID- 25117254
TI - Analysis of L-selectin-mediated cellular interactions under flow conditions.
AB - Lymphocyte homing is mediated by a specific interaction between L-selectin
expressed on lymphocytes and its ligands expressed on high endothelial venules
(HEVs) in lymph nodes under physiological flow conditions. In this chapter, two
methods for detecting L-selectin-mediated cellular interactions under shear
stress mimicking physiological flow conditions are described. First, a modified
Stamper-Woodruff cell-binding assay using leukocytes labeled with a fluorescent
orange dye, CMTMR, is introduced. In this method, leukocytes are allowed to bind
to frozen lymph node sections under shear stress and their binding to HEVs can be
clearly visualized by fluorescence microscopy. Second, a parallel flow chamber
assay is described. In this assay, leukocytes are allowed to roll on L-selectin
ligand-expressing cells under various levels of shear stress and their adhesive
interactions are recorded by a video camera equipped with an inverted microscope.
These methods can be applied to determine the effects of various agents that
might affect L-selectin-mediated lymphocyte homing and recruitment.
PMID- 25117255
TI - Assessment of weak sugar-binding ability using lectin tetramer and membrane-based
glycans.
AB - To consider biological significance of glycosylation of proteins, it is necessary
to evaluate the importance of sugar-recognition processes mediated by lectins.
Though the interaction between sugars and proteins, especially animal lectins, is
quite weak with K d approximately 10(-4) M, cellular and molecular recognitions
mediated via sugar-protein interaction increase their avidity by 1-3 orders of
magnitude by the self-association of both receptors and their ligands on cell
surfaces. To assess the weak interaction between lectins and their sugar ligands,
we established lectin tetramer binding to cell surface glycans using flow
cytometry. This strategy is highly sensitive, and useful to determine whether or
not a putative lectin domain may have sugar-binding ability.
PMID- 25117256
TI - Perspectives in glycomics and lectin engineering.
AB - This chapter would like to provide a short survey of the most promising concepts
applied recently in analysis of glycoproteins based on lectins. The first part
describes the most exciting analytical approaches used in the field of
glycoprofiling based on integration of nanoparticles, nanowires, nanotubes, or
nanochannels or using novel transducing platforms allowing to detect very low
levels of glycoproteins in a label-free mode of operation. The second part
describes application of recombinant lectins containing several tags applied for
oriented and ordered immobilization of lectins. Besides already established
concepts of glycoprofiling several novel aspects, which we think will be taken
into account for future, more robust glycan analysis, are described including
modified lectins, peptide lectin aptamers, and DNA aptamers with lectin-like
specificity introduced by modified nucleotides. The last part of the chapter
describes a novel concept of a glycocodon, which can lead to a better
understanding of glycan-lectin interaction and for design of novel lectins with
unknown specificities and/or better affinities toward glycan target or for
rational design of peptide lectin aptamers or DNA aptamers.
PMID- 25117257
TI - Molecular basis of a pandemic of avian-type influenza virus.
AB - Despite heroic efforts to prevent the emergence of an influenza pandemic, avian
influenza A virus has prevailed by crossing the species barriers to infect humans
worldwide, occasionally with morbidity and mortality at unprecedented levels, and
the virus later usually continues circulation in humans as a seasonal influenza
virus, resulting in health-social-economic problems each year. Here, we review
current knowledge of influenza viruses, their life cycle, interspecies
transmission, and past pandemics and discuss the molecular basis of pandemic
acquisition, notably of hemagglutinin (lectin) acting as a key contributor to
change in host specificity in viral infection.
PMID- 25117258
TI - Basic procedure of x-ray crystallography for analysis of lectin-sugar
interactions.
AB - Most three-dimensional structures of lectins have been determined by X-ray
crystallography. This method determines the molecular structure using X-ray
diffraction of a crystal, thereby providing structural information at the atomic
level. In this chapter, an overview of the method for protein crystallography is
briefly introduced, including a description of several techniques for analysis of
the molecular and sugar-binding structure of lectins.
PMID- 25117259
TI - A new structure determination method of lectins using a selenium-containing sugar
ligand.
AB - Phase determination is essential for solving X-ray crystal structures of proteins
and their complexes. Conventional phase-determination methods using heavy atoms
(Pt, Au, Hg, etc.) or the selenium (Se) atom are routinely utilized in structure
determination of protein crystals. Here, we describe an alternative phase
determination method for proteins such as lectins in which a Se-containing glycan
is used as a ligand. In this technique, the Se atoms are simply introduced into
the protein crystal as a complex, and the phase of the protein can be determined
using anomalous signals from the Se-containing sugar.
PMID- 25117260
TI - NMR analysis of carbohydrate-binding interactions in solution: an approach using
analysis of saturation transfer difference NMR spectroscopy.
AB - One of the most commonly used ligand-based NMR methods for detecting ligand
binding is saturation transfer difference (STD) nuclear magnetic resonance (NMR)
spectroscopy. The STD NMR method is an invaluable technique for assessing
carbohydrate-lectin interactions in solution, because STD NMR can be used to
detect weak ligand binding (Kd ca. 10(-3)-10(-8) M). STD NMR spectra identify the
binding epitope of a carbohydrate ligand when bound to lectin. Further, the STD
NMR method uses 1H-detected NMR spectra of only the carbohydrate, and so only
small quantities of non-labeled lectin are required. In this chapter, I describe
a protocol for the STD NMR method, including the experimental procedures used to
acquire, process, and analyze STD NMR data, using STD NMR studies for methyl-beta
D-galactopyranoside (beta-Me-Gal) binding to the C-terminal domain of an R-type
lectin from earthworm (EW29Ch) as an example.
PMID- 25117261
TI - Small-angle X-ray scattering to obtain models of multivalent lectin-glycan
complexes.
AB - Recent advances in small-angle X-ray scattering (SAXS) have led to the ability to
model the glycans on glycoproteins and to obtain the low-resolution solution
structures of complexes of lectins bound to multivalent glycan-presenting
scaffolds. This progress in SAXS can respond to the increasing interest in the
biological action of glycoproteins and lectins and in the design of multivalent
glycan-based antagonists. Carbohydrates make up a significant part of the X-ray
scattering content in SAXS and should be included in the model together with the
protein, whose structure is most often based on a crystal structure or NMR
ensemble, to give a far-improved fit with the experimental data. The modeling of
the spatial positioning of glycans on proteins or in the architecture of lectin
glycan complexes delivers low-resolution structural information hitherto
unmatched by any other method. SAXS data on the bacterial lectin FimH, strongly
bound to heptyl alpha-D-mannose on a sevenfold derivatized beta-cyclodextrin,
permitted determination of the stoichiometry of the complex and the geometry of
the lectin deposition on the multivalent beta-cyclodextrin. The SAXS methods can
be applied to larger complexes as the technique imposes no limit on the size of
the macromolecular assembly in solution.
PMID- 25117262
TI - Directed evolution of lectins by an improved error-prone PCR and ribosome display
method.
AB - Lectins are useful reagents for the structural characterization of glycans.
However, currently available lectins have an apparent drawback in their
"repertoire," lacking some critical probes, such as those for sulfated glycans.
Thus, engineering lectins with novel specificity would be of great practical
value. Here, we describe a directed evolution strategy to tailor novel lectins
for novel specificity or biological functions. Our strategy uses a reinforced
ribosome display-based selection combined with error-prone PCR to isolate mutants
with target specificity and an evanescent-field fluorescence-assisted
glycoconjugate microarray to rapidly evaluate the specificity of selected
mutants. A successful case of screening a lectin, which has acquired an ability
to recognize 6-sulfo-galactose-terminated glycans, is described.
PMID- 25117263
TI - Tracing ancestral specificity of lectins: ancestral sequence reconstruction
method as a new approach in protein engineering.
AB - Protein evolution is a process of molecular design leading to the diversity of
functional proteins found in nature. Recent advances in bioinformatics and
structural biology, in addition to recombinant protein expression techniques,
enable us to analyze more directly the molecular evolution of proteins by a new
method using ancestral sequence reconstruction (ASR), the so-called experimental
molecular archaeology. ASR has been used to reveal molecular properties and
structures correlating with changing geology, ecology, and physiology, and to
identify the structure elements important to changing physiological functions to
fill substantial gaps in the processes of protein evolution. In this chapter, we
describe ASR as a new method of protein engineering studies, and their
application to analyzing lectins, of which evolutionary processes and structural
features contributing to molecular stability, specificity, and unique functions
have been elucidated. Experimental molecular archeology using ASR and crystal
structures of full-length ancestral proteins is useful in understanding the
evolutionary process of the functional and structural diversified lectins by
tracing ancestral specificities.
PMID- 25117264
TI - Comprehensive list of lectins: origins, natures, and carbohydrate specificities.
AB - More than 100 years have passed since the first lectin ricin was discovered.
Since then, a wide variety of lectins (lect means "select" in Latin) have been
isolated from plants, animals, fungi, bacteria, as well as viruses, and their
structures and properties have been characterized. At present, as many as 48
protein scaffolds have been identified as functional lectins from the viewpoint
of three-dimensional structures as described in this chapter. In this chapter,
representative 53 lectins are selected, and their major properties that include
hemagglutinating activity, mitogen activity, blood group specificity, molecular
weight, metal requirement, and sugar specificities are summarized as a
comprehensive table. The list will provide a practically useful, comprehensive
list for not only experienced lectin users but also many other non-expert
researchers, who are not familiar to lectins and, therefore, have no access to
advanced lectin biotechnologies described in other chapters.
PMID- 25117265
TI - Lectin structures: classification based on the 3-D structures.
AB - Recent progress in structural biology has elucidated the three-dimensional
structures and carbohydrate-binding mechanisms of most lectin families. Lectins
are classified into 48 families based on their three-dimensional structures. A
ribbon drawing gallery of the crystal and solution structures of representative
lectins or lectin-like proteins is appended and may help to convey the diversity
of lectin families, the similarity and differences between lectin families, as
well as the carbohydrate-binding architectures of lectins.
PMID- 25117268
TI - Radiation induced base excision repair (BER): a mechanistic mathematical
approach.
AB - This paper presents a mechanistic model of base excision repair (BER) pathway for
the repair of single-stand breaks (SSBs) and oxidized base lesions produced by
ionizing radiation (IR). The model is based on law of mass action kinetics to
translate the biochemical processes involved, step-by-step, in the BER pathway to
translate into mathematical equations. The BER is divided into two subpathways,
short-patch repair (SPR) and long-patch repair (LPR). SPR involves in replacement
of single nucleotide via Pol beta and ligation of the ends via XRCC1 and Ligase
III, while LPR involves in replacement of multiple nucleotides via PCNA, Pol
delta/E and FEN 1, and ligation via Ligase I. A hallmark of IR is the production
of closely spaced lesions within a turn of DNA helix (named complex lesions),
which have been attributed to a slower repair process. The model presented
considers fast and slow component of BER kinetics by assigning SPR for simple
lesions and LPR for complex lesions. In the absence of in vivo reaction rate
constants for the BER proteins, we have deduced a set of rate constants based on
different published experimental measurements including accumulation kinetics
obtained from UVA irradiation, overall SSB repair kinetic experiments, and
overall BER kinetics from live-cell imaging experiments. The model was further
used to calculate the repair kinetics of complex base lesions via the LPR
subpathway and compared to foci kinetic experiments for cells irradiated with
gamma rays, Si, and Fe ions. The model calculation show good agreement with
experimental measurements for both overall repair and repair of complex lesions.
Furthermore, using the model we explored different mechanisms responsible for
inhibition of repair when higher LET and HZE particles are used and concluded
that increasing the damage complexity can inhibit initiation of LPR after the AP
site removal step in BER.
PMID- 25117266
TI - Structural basis for constitutive activity and agonist-induced activation of the
enteroendocrine fat sensor GPR119.
AB - BACKGROUND AND PURPOSE: GPR119 is a Galphas-coupled 7TM receptor activated by
endogenous lipids such as oleoylethanolamide (OEA) and by the dietary
triglyceride metabolite 2-monoacylglycerol. GPR119 stimulates enteroendocrine
hormone and insulin secretion. But despite massive drug discovery efforts in the
field, very little is known about the basic molecular pharmacology of GPR119.
EXPERIMENTAL APPROACH: GPR119 receptor signalling was studied in transfected
cells. Mutational mapping (30 mutations in 23 positions) was performed on
residues required for ligand-independent and agonist-induced GPR119 activation
(AR231453 and OEA). Novel Rosetta-based receptor modelling was applied, using a
composite template approach with segments from different X-ray structures and
fully flexible ligand docking. KEY RESULTS: The increased signalling induced by
increasing the cell surface expression of GPR119 in the absence of agonist and
the inhibitory effect of two synthetic inverse agonists demonstrated that GRP119
signals with a high degree of constitutive activity through the Galphas pathway.
The mutational maps for AR231453 and OEA were very similar and, surprisingly,
also similar to the mutational map for residues affecting the constitutive
signalling - albeit with key differences. Surprisingly, almost all residues in
extracellular loop-2b were important for the constitutive activity. The molecular
modelling and docking demonstrated that AR231453 binds in a 'vertical' pocket in
between mutational hits reaching from the centre of the receptor out to
extracellular loop-2b. CONCLUSIONS AND IMPLICATIONS: The high constitutive
activity of GPR119 should be taken into account in future drug discovery efforts,
which can now be guided by the detailed knowledge of the physiochemical
properties of the extended ligand-binding pocket.
PMID- 25117270
TI - Normative values of major SCAT2 and SCAT3 components for a college athlete
population.
AB - The Sports Concussion Assessment Tool-2 (SCAT2) is a posttrauma evaluative
screener for concussion. Although a revised version (SCAT3) recently was
released, the SCAT2 continues in use. Moreover, there have been no reports of
normative values with college athletes with the SCAT2 or SCAT3. Similar to the
SCAT3, the SCAT2 includes a 22-item self-report symptom scale, the Standardized
Assessment of Concussion (SAC), and a hard surface-only version of the Balance
Error Scoring System (BESS). The SCAT3 does not employ a total score and adds an
optional gait component. The purpose of this study was to develop normative
values for collegiate athletes on the SCAT2 and its subparts with respect to sex,
collision risk by sport, and concussion history. In preseason, 477 college
athletes (332 male, 145 female) completed the SCAT2. The average total score was
91.08 (SD = 5.60). The average number of symptoms endorsed was 1.75. Average SAC
and BESS scores were 27.17 (SD = 2.01) and 25.64 (SD = 4.07), respectively.
Little or no difference was found in total and component scores due to sex, sport
type, or concussion history. When baseline measurement is lacking, these data
provide a good benchmark for interpreting SCAT2 and SCAT3 performance.
PMID- 25117269
TI - Do tree-ring stable isotope compositions faithfully record tree carbon/water
dynamics?
PMID- 25117271
TI - The use of FM dyes to analyze plant endocytosis.
AB - FM (Fei-Mao) styryl dyes are compounds of amphiphilic character that are used for
the fluorescence tracking of endocytosis and related processes, i.e., the
internalization of membrane vesicles from the plasma membrane (PM) and dynamics
of endomembranes. Staining with FM dyes and subsequent microscopical observations
could be performed both on the tissue and cellular level. Here, we describe
simple procedures for the effective FM dye staining and de-staining in root
epidermal cells of Arabidopsis thaliana seedlings and suspension-cultured tobacco
cells. The progression of FM dye uptake, reflected by an increased amount of the
dye in the endosomal compartments, is monitored under the fluorescence microscope
in a time-lapse manner. The data obtained can be used for the characterization of
the rate of endocytosis and the function of components of endosomal recycling
machinery.
PMID- 25117267
TI - Evolution of nonclassical MHC-dependent invariant T cells.
AB - TCR-mediated specific recognition of antigenic peptides in the context of
classical MHC molecules is a cornerstone of adaptive immunity of jawed
vertebrate. Ancillary to these interactions, the T cell repertoire also includes
unconventional T cells that recognize endogenous and/or exogenous antigens in a
classical MHC-unrestricted manner. Among these, the mammalian nonclassical MHC
class I-restricted invariant T cell (iT) subsets, such as iNKT and MAIT cells,
are now believed to be integral to immune response initiation as well as in
orchestrating subsequent adaptive immunity. Until recently the evolutionary
origins of these cells were unknown. Here we review our current understanding of
a nonclassical MHC class I-restricted iT cell population in the amphibian Xenopus
laevis. Parallels with the mammalian iNKT and MAIT cells underline the crucial
biological roles of these evolutionarily ancient immune subsets.
PMID- 25117272
TI - Sterol dynamics during endocytic trafficking in Arabidopsis.
AB - Sterols are lipids found in membranes of eukaryotic cells. Functions of sterols
have been demonstrated for various cellular processes including endocytic
trafficking in animal, fungal, and plant cells. The ability to visualize sterols
at the subcellular level is crucial to understand sterol distribution and
function during endocytic trafficking. In plant cells, the polyene antibiotic
filipin is the most extensively used tool for the specific detection of
fluorescently labeled 3-beta-hydroxysterols in situ. Filipin can to some extent
be used to track sterol internalization in live cells, but this application is
limited, due to the inhibitory effects filipin exerts on sterol-dependent
endocytosis. Nevertheless, filipin-sterol labeling can be performed on aldehyde
fixed cells which allows for sterol detection in endocytic compartments. This
approach can combine studies correlating sterol distribution with experimental
manipulations of endocytic trafficking pathways. Here, we describe step-by-step
protocols and troubleshooting for procedures on live and fixed cells to visualize
sterols during endocytic trafficking. We also provide a detailed discussion of
advantages and limitations of both methods. Moreover, we illustrate the use of
the endocytic recycling inhibitor brefeldin A and a genetically modified version
of one of its target molecules for studying endocytic sterol trafficking.
PMID- 25117273
TI - Live microscopy analysis of endosomes and vesicles in tip-growing root hairs.
AB - Tip growth is one of the most preferable models in the study of plant cell
polarity; cell wall deposition is restricted mainly to a certain area of the
cell, and cell expansion at this specific area leads to the development of
tubular outgrowth. Tip-growing root hairs are well-established systems for such
studies, because their lateral position within the root makes them easily
accessible for experimental approaches and microscopic observations. Fundamental
structural and molecular processes driving tip growth are exocytosis,
endocytosis, and all aspects of vesicular and endosomal dynamic trafficking, as
related to targeted membrane flow. Study of vesicles and endosomes in living root
hairs, however, is rather difficult, due to their small size and due to the
resolution limits of conventional light microscopes. Here we present noninvasive
approaches for visualizing vesicular and endosomal compartments in the tip of
growing root hairs using electronic light microscopy, contrast-enhanced video
light microscopy, and confocal laser scanning microscopy (CLSM). These methods
allow utilizing the maximum resolution of the light microscope. Together with
protocols for appropriate preparation of living plant samples, the described
methods should help improve our understanding on how tiny vesicles and endosomes
support the process of tip growth in root hairs.
PMID- 25117274
TI - Analysis of fluid-phase endocytosis in (intact) plant cells.
AB - Endocytosis is a continuous process at the plasma membrane at least of all
eukaryotic cells. Regardless of the molecular machinery, which drives the
formation and uptake of endocytic vesicles, it is reasonable to assume that this
process inevitably collects external fluid. Hence, at least for the majority of
apoplastic solutes, the endocytosis of the fluid phase is likely to be an
inevitable process. Due to its independence from the molecular machinery and low
selectivity with respect to the cargo, it is thus perfectly suited to be used as
a tracer to follow the activity of all endocytic events. Here we describe simple
protocols based on fluorescence microscopy, which yield quantitative information
about endocytic vesicle sizes-with sub-diffraction accuracy-as well as the size
exclusion limits for these uptake routes.
PMID- 25117275
TI - Immunogold labeling and electron tomography of plant endosomes.
AB - High-resolution imaging of endosomal compartments and associated organelles can
be achieved using state-of-the-art electron microscopy techniques, such as the
combination of cryofixation/freeze-substitution for sample processing and
electron tomography for three-dimensional (3D) analysis. This chapter deals with
the main steps associated with these imaging techniques: selection of samples
suitable for studying plant endosomes, sample preparation by high-pressure
freezing/freeze-substitution, and electron tomography of plastic sections. In
addition, immunogold approaches for identification of subcellular localization of
endosomal and cargo proteins are also discussed.
PMID- 25117277
TI - Analysis of Rab GTPase-effector interactions by bimolecular fluorescence
complementation.
AB - RAB GTPases interact with specific effector molecules in a spatiotemporally
regulated manner to induce various downstream reactions. To clarify the overall
picture of RAB GTPase functions, it is important to elucidate the cellular locale
where RAB and its effectors interact. Here, we applied a bimolecular fluorescence
complementation (BiFC) assay to analyze where RAB GTPase interacted with
effectors in endosomal trafficking.
PMID- 25117276
TI - Investigating protein-protein interactions in the plant endomembrane system using
multiphoton-induced FRET-FLIM.
AB - Real-time noninvasive fluorescence-based protein assays enable a direct access to
study interactions in their natural environment and hence overcome the
limitations of other methods that rely on invasive cell disruption techniques.
The determination of Forster resonance energy transfer (FRET) by means of
fluorescence lifetime imaging microscopy (FLIM) is currently the most advanced
method to observe protein-protein interactions at nanometer resolution inside
single living cells and in real-time. In the FRET-FLIM approach, the information
gained using steady-state FRET between interacting proteins is considerably
improved by monitoring changes in the excited-state lifetime of the donor
fluorophore where its quenching in the presence of the acceptor is evidence for a
direct physical interaction. The combination of confocal laser scanning
microscopy with the sensitive advanced technique of time-correlated single photon
counting allows the mapping of the spatial distribution of fluorescence lifetimes
inside living cells on a pixel-by-pixel basis that is the same as the
fluorescence image. Moreover, the use of multiphoton excitation particularly for
plant cells provides further advantages such as reduced phototoxicity and
photobleaching. In this protocol, we briefly describe the instrumentation and
experimental design to study protein interactions within the plant endomembrane
system, with a focus on the imaging of plant cells expressing fluorescent
proteins and acquisition and analysis of fluorescence lifetime resolved data.
PMID- 25117278
TI - In vivo imaging of brassinosteroid endocytosis in Arabidopsis.
AB - Increasing evidence shows the involvement of endocytosis in specific signaling
outputs in plants. To better understand the interplay between endocytosis and
signaling in plant systems, more ligand-receptor pairs need to be identified and
characterized. Crucial for the advancement of this research is also the
development of imaging techniques that allow the visualization of endosome
associated signaling events at a high spatiotemporal resolution. This requires
the establishment of tools to track ligands and their receptors by fluorescence
microscopy in living cells. The brassinosteroid (BR) signaling pathway has been
among the first systems to be characterized with respect to its connection with
endocytic trafficking, owning to the fact that a fluorescent version of BR, Alexa
Fluor 647-castasterone (AFCS) has been generated. AFCS and the fluorescently
tagged BR receptor, BR INSENSITIVE1 (BRI1) have been used for the specific
detection of BRI1-AFCS endocytosis and for the delineation of their endocytic
route as being clathrin-mediated. AFCS was successfully applied in functional
studies in which pharmacological rerouting of the BRI1-BR complex was shown to
have an impact on signaling. Here we provide a method for the visualization of
endocytosis of plant receptors in living cells. The method was used to track
endocytosis of BRI1-BR complexes in Arabidopsis epidermal root meristem cells by
using fluorescent BRs. Pulse-chase experiments combined with quantitative
confocal microscopy were used to determine the internalization rates of BRs. This
method is well suited to measure the internalization of other plant receptors if
fluorescent ligands are available.
PMID- 25117279
TI - Analysis of prevacuolar compartment-mediated vacuolar proteins transport.
AB - Transient expression using protoplasts is a quick and powerful tool for studying
protein trafficking and subcellular localization in plant cells. Prevacuolar
compartments (PVCs) or multivesicular bodies (MVBs) are intermediate compartments
that mediate protein transport between late Golgi or trans-Golgi network (TGN)
and vacuole. Both wortmannin treatment and ARA7(Q69L) expression can induce PVC
homotypic fusion and PVC enlargement in plant cells. Here, we describe detailed
protocols to use transient expression of protoplasts derived from Arabidopsis
suspension culture cells for studying protein trafficking and localization. Using
three GFP-tagged vacuolar cargo proteins and RFP-tagged PVC membrane marker as
examples, we illustrate the major tools and methods, including wortmannin
treatment, ARA7(Q69L) expression and immunoblot analysis, to analyze PVC-mediated
vacuolar protein transport in plant cells.
PMID- 25117280
TI - Evaluation of defective endosomal trafficking to the vacuole by monitoring seed
storage proteins in Arabidopsis thaliana.
AB - Vacuolar proteins are synthesized as precursor forms in the endoplasmic reticulum
and are sorted to the vacuole. In this chapter, we introduce two easy methods for
the evaluation of vacuolar protein transport using Arabidopsis seeds. These
methods are adequate to detect defects in vacuolar transport mediated by
endosomes and other trafficking pathways as well. They include an immunoblot
assay that monitors the abnormal accumulation of storage protein precursors, and
an immunogold labeling assay that monitors the abnormal secretion of storage
proteins. Each method facilitates the rapid identification of defects in the
transport of endogenous vacuolar proteins in Arabidopsis mutants.
PMID- 25117281
TI - Trans-species complementation analysis to study function conservation of plant
Endosomal Sorting Complex Required for Transport (ESCRT) proteins.
AB - ESCRT (Endosomal Sorting Complex Required for Transport) proteins are required
for the sorting of biosynthetic and endocytic proteins at multivesicular bodies
(MVBs). Here, I describe an assay to evaluate conservation of endosomal sorting
functions of plant ESCRT proteins by trans-species complementation analysis. The
assay is based on the imaging of a fluorescent biosynthetic MVB cargo, the
carboxypeptidase S (CPS) fused to the green fluorescent protein GFP, in yeast
ESCRT mutants expressing putative plant orthologues of the missing yeast ESCRT
components.
PMID- 25117282
TI - A re-elicitation assay to correlate flg22-signaling competency with ligand
induced endocytic degradation of the FLS2 receptor.
AB - In the model plant Arabidopsis, the best studied Pattern-triggered immunity (PTI)
system is perception of the bacterial pathogen-associated molecular pattern
(PAMP) flagellin, or its active peptide-derivative flg22, by the plasma membrane
localized receptor FLAGELLIN SENSING 2 (FLS2). Flg22 perception initiates an
array of immune responses including the fast and transient production of reactive
oxygen species (ROS). In addition, FLS2 undergoes ligand-induced endocytosis and
subsequent degradation within 60 min of flg22-treatment. Luminol-based assays are
routinely used to measure extracellular ROS production within minutes after flg22
treatment. Many mutants in flg22-response pathways display defects in flg22
induced ROS production. Here, we describe a luminol-based ROS Re-elicitation
Assay that can be utilized to quantitatively assess flg22-signaling competency of
FLS2 at times during which FLS2 is internalized, trafficked through endosomal
compartments, and degraded in response to flg22. This assay may also be employed
to correlate FLS2 signaling competency with receptor accumulation in vesicular
trafficking mutants that either affect FLS2 endocytosis or replenishment of FLS2
through the secretory pathway. In addition, this assay can be extended to studies
of other PAMP (ligand)-receptor pairs.
PMID- 25117283
TI - Preparation of enriched plant clathrin-coated vesicles by differential and
density gradient centrifugation.
AB - Methods for the subcellular fractionation and enrichment of specific
intracellular compartments are essential tools in the analysis of compartment
composition and function. In vitro characterization of isolated cell organelles
and other endomembrane intermediates, including exploration of the compartment
protein ensemble, offers strong clues of in vivo function identity. Here, we
describe methodology for the isolation of clathrin-coated vesicles from
Arabidopsis thaliana suspension-cultured cells on the basis of differential and
density centrifugation.
PMID- 25117284
TI - Proteomics of endosomal compartments from plants case study: isolation of trans
Golgi network vesicles.
AB - A detailed understanding of endomembrane processes and their biological roles is
vital for a complete picture of plant growth and development; however their
highly dynamic nature has complicated comprehensive and rigorous studies so far.
Recent pioneering efforts have demonstrated that isolation of vesicles in their
native state, paired with a quantitative identification of their cargo, offers a
viable and practicable approach for the dissection of endomembrane trafficking
pathways. The protocol presented in this chapter describes in detail the
isolation of the SYP61 trans-Golgi network vesicles from Arabidopsis. With minor
alterations, in a few key parameters, it can be adopted to yield a universal
procedure for the broad spectrum of plant vesicles.
PMID- 25117285
TI - Analysis of global ubiquitylation and ubiquitin-binding domains involved in
endosomal trafficking.
AB - Ubiquitylation is a reversible posttranslational modification that regulates
various cellular pathways. Ubiquitylation of a plasma membrane protein was shown
to serve as a signal for endocytosis of plasma membrane proteins in yeast and
mammals as well as in plants. As more and more plant plasma membrane proteins are
reported to be regulated through their ubiquitylation status, methods to analyze
ubiquitylation and ubiquitin binding would be useful for the characterization of
proteins involved in endocytosis of ubiquitylated cargo proteins.
PMID- 25117286
TI - Analysis of endocytosis and ubiquitination of the BOR1 transporter.
AB - Endocytosis and membrane trafficking are the major factors controlling the
abundance of plasma membrane proteins, such as transporters and receptors. We
have found that Arabidopsis borate transporter BOR1 is polarly localized to the
inner (stele-facing) plasma membrane domain of various root cells under boron
limitation, and when boron is supplied in excess, BOR1 is rapidly transferred to
the vacuole for immediate degradation. The BOR1 polarity and degradation are
controlled by membrane trafficking including endocytosis. In this chapter, we
describe methods for observation of endocytic trafficking of BOR1, and detection
of BOR1 ubiquitination that is required for vacuolar sorting for degradation.
PMID- 25117288
TI - Ubiquitylation-mediated control of polar auxin transport: analysis of Arabidopsis
PIN2 auxin transport protein.
AB - Reversible, covalent modification by the small protein ubiquitin acts in a
variety of pathways controlling protein fate in virtually all aspects of cellular
function. For example, ubiquitylation of plasma membrane proteins modulates their
intracellular sorting and turnover, thereby decisively influencing crosstalk
between cells and their environment. In recent years, experimental work performed
with the model plant Arabidopsis thaliana demonstrated ubiquitylation of a number
of plasma membrane proteins, including the auxin efflux carrier protein PIN2. By
using solubilized membrane protein immunoprecipitation assays, we established
quantitative approaches, suitable for analysis of PIN2 ubiquitylation and
variations therein. Applicability of this robust approach is not restricted to
PIN auxin carriers, but could be extended to analysis of further plant membrane
proteins that are controlled by variations in their ubiquitylation status.
PMID- 25117289
TI - Chemical genomics screening for biomodulators of endomembrane system trafficking.
AB - Cell proteins traffic through complex and tightly regulated pathways. Although
the endomembrane system is essential, its different pathways are still not well
understood. In order to dissect protein trafficking pathways, chemical genomic
screenings have been performed. This strategy has been utilized to successfully
discover bioactive chemicals with a specific cellular action and in most cases,
tunable and reversible effects. Once the bioactive chemical is identified,
further strategies can be used to find the target proteins that are important for
functionality of trafficking pathways. This approach can be combined with the
powerful genetic tools available for model organisms. Drug-hypersensitive and
drug-resistant mutant isolation can lead to the identification of cellular
pathways affected by a bioactive chemical and reveal its protein target(s). Here,
we describe an approach to look for hypersensitive and resistant mutants to a
specific bioactive chemical that affects protein trafficking in yeast. This
approach can be followed and adapted to any other pathway or cellular process
that can be screened phenotypically, serving as a guide for novel screens in
yeast. More importantly, information provided by this approach can potentially be
extrapolated to other organisms like plants. Thus, the method described can be of
broad utility to plant biologists.
PMID- 25117287
TI - Ubiquitination of plant immune receptors.
AB - Ubiquitin is a highly conserved regulatory protein consisting of 76 amino acids
and ubiquitously expressed in all eukaryotic cells. The reversible ubiquitin
conjugation to a wide variety of target proteins, a process known as
ubiquitination or ubiquitylation, serves as one of the most important and
prevalent posttranslational modifications to regulate the myriad actions of
protein cellular functions, including protein degradation, vesicle trafficking,
and subcellular localization. Protein ubiquitination is an ATP-dependent stepwise
covalent attachment of one or more ubiquitin molecules to target proteins
mediated by a hierarchical enzymatic cascade consisting of an E1 ubiquitin
activating enzyme, E2 ubiquitin-conjugating enzyme, and E3 ubiquitin ligase. The
plant plasma membrane resident receptor-like kinase Flagellin Sensing 2 (FLS2)
recognizes bacterial flagellin and initiates innate immune signaling to defend
against pathogen attacks. We have recently shown that two plant U-box E3
ubiquitin ligases PUB12 and PUB13 directly ubiquitinate FLS2 and promote
flagellin-induced FLS2 degradation, which in turn attenuates FLS2 signaling to
prevent excessive or prolonged activation of immune responses. Here, we use FLS2
as an example to describe a protocol for detection of protein ubiquitination in
plant cells in vivo and in test tubes in vitro. In addition, we elaborate the
approach to identify different types of ubiquitin linkages by using various
lysine mutants of ubiquitin. The various in vivo and in vitro ubiquitination
assays will provide researchers with the tools to address how ubiquitination
regulates diverse cellular functions of target proteins.
PMID- 25117290
TI - Integrative chemical proteomics and cell biology methods to study endocytosis and
vesicular trafficking in Arabidopsis.
AB - We present a comprehensive approach combining proteomics and cell biology to
study vesicular trafficking in plants. Within this approach, we exploit chemical
compounds inhibiting particular vesicular trafficking events in plant cells.
Treatment of plants with these relatively specific inhibitors results in
intracellular accumulation of proteins being transported by vesicles as well as
in a change in abundance of regulatory proteins. Such pharmacological inhibition
allows for identification of key proteins, and for further detailed functional
investigation using cell biological, molecular biological, and biochemical
methods used for validation of proteomic results.
PMID- 25117291
TI - Protons modulate perivascular axo-axonal neurotransmission in the rat mesenteric
artery.
AB - BACKGROUND AND PURPOSE: Previous studies have demonstrated that nicotine releases
protons from adrenergic nerves via stimulation of nicotinic ACh receptors and
activates transient receptor potential vanilloid-1 (TRPV1) receptors located on
calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves,
resulting in vasodilatation. The present study investigated whether perivascular
nerves release protons, which modulate axon-axonal neurotransmission. EXPERIMENT
APPROACH: Perfusion pressure and pH levels of perfusate in rat-perfused
mesenteric vascular beds without endothelium were measured with a pressure
transducer and a pH meter respectively. KEY RESULTS: Periarterial nerve
stimulation (PNS) initially induced vasoconstriction, which was followed by long
lasting vasodilatation and decreased pH levels in the perfusate. Cold-storage
denervation of the preparation abolished the decreased pH and vascular responses
to PNS. The adrenergic neuron blocker guanethidine inhibited PNS-induced
vasoconstriction and effects on pH, but not PNS-induced vasodilatation. Capsaicin
(CGRP depletor), capsazepine and ruthenium red (TRPV1 inhibitors) attenuated the
PNS-induced decrease in pH and vasodilatation. In denuded preparations, ACh
caused long-lasting vasodilatation and lowered pH; these effects were inhibited
by capsaicin pretreatment and atropine, but not by guanethidine or mecamylamine.
Capsaicin injection induced vasodilatation and a reduction in pH, which were
abolished by ruthenium red. The use of a fluorescent pH indicator demonstrated
that application of nicotine, ACh and capsaicin outside small mesenteric arteries
reduced perivascular pH levels and these effects were abolished in a Ca(2+) -free
medium. CONCLUSION AND IMPLICATION: These results suggest that protons are
released from perivascular adrenergic and CGRPergic nerves upon PNS and these
protons modulate transmission in CGRPergic nerves.
PMID- 25117292
TI - Actigraphy and Sleep Diary Measurements in Breast Cancer Survivors: Discrepancy
in Selected Sleep Parameters.
AB - This analysis examined the discrepancy between sleep diary and actigraphy
measurements in breast cancer survivors (BCS) with insomnia. BCS from communities
in Western U.S. provided demographic/medical information, insomnia, mood, and
fatigue data at baseline. Averaged over 5 weeks, actigraphy measured 55.75
minutes (SD = 112.42) less total sleep time (TST), and 85.19 minutes (SD = 81.36)
more wake after sleep onset (WASO) than diaries. Some women showed agreement
between measures; others were more variable. There were no significant
relationships between TST and WASO discrepancy and participant characteristics.
There may be sleep differences in BCS that results in greater perceived TST and
less WASO reported in diaries. Measurements discrepancy is a significant concern
needing further evaluation of medical populations with insomnia.
PMID- 25117294
TI - Anti-CCR4 monoclonal antibody mogamulizumab for the treatment of EBV-associated T
and NK-cell lymphoproliferative diseases.
AB - PURPOSE: Epstein-Barr virus (EBV) infects not only B cells but also T cells and
natural killer (NK) cells, and T- and NK-cell lymphoproliferative diseases (T/NK
LPD) that are refractory to conventional chemotherapies may develop. To identify
a molecular-targeted therapy for EBV-associated T/NK-LPDs, we investigated
whether CC chemokine receptor 4 (CCR4) was expressed on EBV-infected T and/or NK
cells and whether a humanized anti-CCR4 monoclonal antibody, mogamulizumab, was
effective. EXPERIMENTAL DESIGN: CCR4 expression was examined in various cell
lines. In vitro, the effects of mogamulizumab on cell lines were evaluated in the
presence of peripheral blood mononuclear cells from volunteers. In vivo, the
effects of mogamulizumab were evaluated using a murine xenograft model. CCR4
expression was examined on EBV-infected cells from patients with EBV-associated
T/NK-LPDs. Ex vivo, the effects of mogamulizumab were evaluated using patient
lymphocytes. RESULTS: CCR4 expression was confirmed in most EBV-positive T and NK
cell lines. Mogamulizumab induced antibody-dependent cellular cytotoxicity (ADCC)
activity against CCR4-positive cell lines, and inhibited the growth of EBV
positive NK-cell lymphomas in a murine xenograft model. Furthermore, CCR4 was
expressed on EBV-infected cells in 8 of 17 patients with EBV-associated T/NK
LPDs. Interestingly, CCR4 was positive in 5 of 5 patients with hydroa
vacciniforme, a photodermatosis caused by the clonal expansion of EBV-infected
gammadeltaT cells. EBV-positive gammadeltaT cells were obtained from a patient
with hydroa vacciniforme and subjected to an antibody-dependent cell-mediated
cytotoxicity (ADCC) assay. The gammadeltaT cells that were positive for CCR4 were
killed by mogamulizumab via ADCC. CONCLUSIONS: These results indicate that
mogamulizumab may be a therapeutic option against EBV-associated T/NK-LPDs.
PMID- 25117300
TI - An abrasion-resistant and broadband antireflective silica coating by block
copolymer assisted sol-gel method.
AB - A double-layer broadband antireflective (AR) coating was prepared on glass
substrate via sol-gel process using two kinds of acid-catalyzed TEOS-derived
silica sols. The relative dense layer with a porosity of ~10% was obtained from
an as-prepared sol, while the porous layer with a porosity of ~55% was from a
modified one with block copolymer (BCP) Pluronic F127 as template which results
in abundant ordered mesopores. The two layers give rise to a reasonable
refractive index gradient from air to the substrate and thus high transmittance
in a wide wavelength range, and both of them have the same tough skeleton despite
different porosity, for which each single-layer and the double-layer coatings all
behaved well in the mechanical property tests. The high transmittance and the
strong ability of resisting abrasion make this coating promising for applications
in some harsh conditions. In addition, the preparation is simple, low-cost, time
saving, and flexible for realizing the optical property.
PMID- 25117299
TI - Cumulative effects of genetic markers and the detection of advanced colorectal
neoplasias by population screening.
AB - Genetic markers associated with colorectal cancer may be used in population
screening for the early identification of patients at elevated risk of disease.
We genotyped 3059 individuals with no cancer family history for eight markers
previously associated with colorectal cancer. After colonoscopy, the genetic
profile of cases with advanced colorectal neoplasia (213) was compared with the
rest (2846). rs2066847 and rs6983267 were significantly associated with the risk
of advanced colorectal neoplasia but with limited effect on their own [odds ratio
(OR) 1.59; 95% confidence interval (CI) 1.02-2.41; p = 0.033 and OR 1.45; 95% CI
1.02-2.12; p = 0.044, respectively]. Cumulative effects, in contrast, were
associated with high risk: the combination of rs2066847, rs6983267, rs4779584,
rs3802842 and rs4939827 minimized the number of markers considered, while
maximizing the relative size of the carrier group and the risk associated to it,
for example, for at least two cumulated risk markers, OR is 2.57 (95% CI 1.50
4.71; corrected p-value 0.0079) and for three or more, OR is 3.57 (95% CI 1.91
6.96; corrected p-value 0.00074). The identification of cumulative models of -
otherwise - low-risk markers could be valuable in defining risk groups, within an
otherwise low-risk population (no cancer family history).
PMID- 25117293
TI - Combined inhibition of Wee1 and PARP1/2 for radiosensitization in pancreatic
cancer.
AB - PURPOSE: While the addition of radiation to chemotherapy improves survival in
patients with locally advanced pancreatic cancer, more effective therapies are
urgently needed. Thus, we investigated the radiosensitizing efficacy of the novel
drug combination of Wee1 and PARP1/2 inhibitors (AZD1775 and olaparib,
respectively) in pancreatic cancer. EXPERIMENTAL DESIGN: Radiosensitization of
AsPC-1 or MiaPaCa-2 human pancreatic cancer cells was assessed by clonogenic
survival and tumor growth assays. Mechanistically, the effects of AZD1775,
olaparib, and radiation on cell cycle, DNA damage (gammaH2AX), and homologous
recombination repair (HRR) were determined. RESULTS: Treatment of AsPC-1 and
MiaPaCa-2 cells with either AZD1775 or olaparib caused modest radiosensitization,
whereas treatment with the combination significantly increased
radiosensitization. Radiosensitization by the combination of AZD1775 and olaparib
was associated with G2 checkpoint abrogation and persistent DNA damage. In
addition, AZD1775 inhibited HRR activity and prevented radiation-induced Rad51
focus formation. Finally, in vivo, in MiaPaCa-2-derived xenografts, olaparib did
not radiosensitize, whereas AZD1775 produced moderate, yet significant,
radiosensitization (P < 0.05). Importantly, the combination of AZD1775 and
olaparib produced highly significant radiosensitization (P < 0.0001) evidenced by
a 13-day delay in tumor volume doubling (vs. radiation alone) and complete
eradication of 20% of tumors. CONCLUSIONS: Taken together, these results
demonstrate the efficacy of combined inhibition of Wee1 and PARP inhibitors for
radiosensitizing pancreatic cancers and support the model that Wee1 inhibition
sensitizes cells to PARP inhibitor-mediated radiosensitization through inhibition
of HRR and abrogation of the G2 checkpoint, ultimately resulting in unrepaired,
lethal DNA damage and radiosensitization. Clin Cancer Res; 20(19); 5085-96.
(c)2014 AACR.
PMID- 25117301
TI - Administration of commercial Rhodococcus equi specific hyperimmune plasma results
in variable amounts of IgG against pathogenic bacteria in foals.
AB - Rhodococcus equi is the most common cause of pneumonia in young foals. A vaccine
is not available and the use of R equi-specific hyperimmune plasma (HIP) is
common. Despite its widespread use, the efficacy of HIP in preventing disease
remains controversial. The objectives of this study were (1) to evaluate the
virulence associate protein A (VapA)-specific IgG and IgG subclasses in
commercially available R equi HIP and (2) to evaluate serum VapA-specific IgG and
IgG subclasses in foals following administration of commercial R equi HIP. Three
different lots from four commercial R equi HIP were sampled. VapA-specific IgG
and IgG subclasses were evaluated in all samples using an ELISA. Serum was
collected from newborn foals either after commercial R equi HIP was administered
(n=97) or not (n=70). Serum was also collected from each mare. Administration of
HIP significantly (P<0.001) increased VapA-specific IgGs in recipient foals,
however, there was a marked variation in VapA-specific IgGs in foals receiving
the same product. VapA-specific IgGs were significantly different (P<0.001)
between products and varied between lots, with coefficients of variation ranging
from 17 to 123 per cent. These results may explain previously reported
disparities in HIP efficacy.
PMID- 25117303
TI - Cross-leg repair of large soft-tissue defects in distal sites of the feet by
distally based neuro-fasciocutaneous flaps with perforating vessels.
AB - The objective of this study was to introduce a method for repairing large soft
tissue defects on the foot. Distally based neuro-fasciocutaneous flaps with
perforating vessels were designed along the saphenous and sural neurovascular
axes. The cutaneous perforating branches of the major arteries of the lower
extremities were used as pedicles, which provided a rotation arc for the cross
leg flap to cover the large-sized soft-tissue defects on the foot. We transferred
6 neurocutaneous vascular axial flaps, including 4 saphenous neurocutaneous axial
flaps (ranging from 25 x 13 to 17 x 9 cm in area) with posterior tibial
perforators as the pedicle, and 2 sural neurocutaneous axial flaps (ranging from
29 x 12 to 18 x 7 cm in area) supplied by the perforating branches of the
peroneal vessels. These 6 cases of neuro-fasciocutaneous flaps survived with
satisfactory cosmetic appearances and functional results on follow-up at 8 to 17
months post-surgery. Placing a distally based neuro-fasciocutaneous cross-leg
flap with perforating vessels is an effective method for repairing large-sized
soft-tissue defects on the foot.
PMID- 25117302
TI - Increased serum levels of GDF-15 associated with mortality and subclinical
atherosclerosis in patients on maintenance hemodialysis.
AB - BACKGROUND/AIMS: Increased carotid intima-media thickness (CIMT) was shown to be
an independent predictor of cardiovascular (CV) mortality in dialysis patients
and the general population. Growth differentiation factor 15 (GDF-15), a member
of the transforming growth factor superfamily, is produced by cardiomyocytes and
atherosclerotic lesions under stress conditions such as inflammation. We assessed
associations between serum concentrations of GDF-15, mortality, and CIMT for
subclinical atherosclerosis in hemodialysis (HD) patients. METHODS: A total of 87
patients on maintenance hemodialysis and 45 sex- and age-matched healthy controls
were included in this prospective study. Serum GDF-15 levels were measured by
ELISA. CIMT was assessed by Doppler ultrasonography. The association between
serum GDF-15 levels and mortality was assessed using Cox regression analysis with
serum levels categorized into two groups according to the median value (328.18
pg/ml). Patients were followed for 2 years and cause-specific and all-cause
mortality were determined. RESULTS: The median level of serum GDF-15 was
significantly higher in HD patients than controls [328 (198-522) vs. 176 (101
289) pg/ml, p < 0.01, respectively]. Serum GDF-15 levels were correlated to CIMT
(r = 0.607, p < 0.001), C-reactive protein (CRP; r = 0.250, p = 0.010), HD
duration (r = 0.376, p = 0.004), and serum albumin (r = - 0.156, p = 0.030). The
multivariate analysis revealed that GDF-15 was found to be an independent
variable of CIMT in HD patients. In the study, the serum GDF-15 level was an
independent marker of all-cause of mortality when adjusted for age, CRP, and
history of diabetes mellitus. CONCLUSION: The relationship between serum GDF-15,
mortality, and carotid artery thickening suggests that GDF-15 may be a novel
marker of atherosclerosis, inflammation, and malnutrition in HD patients.
PMID- 25117304
TI - Assessment of microsatellites in estimating inter- and intraspecific variation
among Neotropical Crocodylus species.
AB - We tested microsatellites that were developed for the saltwater crocodile
(Crocodylus porosus) for cross-species amplification and to provide an estimate
of inter- and intraspecific variation among four species of Neotropical
crocodiles (C. rhombifer, C. intermedius, C. acutus, and C. moreletii). Our
results indicated that with the exception of 2 loci in C. intermedius, all 10
microsatellite loci were successfully amplified in the 4 species, producing a set
of variably sized alleles that ranged in number between 2 and 14 alleles per
locus. Similarly, private alleles (i.e., unique alleles) also were reported in
all 4 species for at least 3 loci. The mean observed and expected
heterozygosities (averaged across species for all 10 loci combined) ranged from
0.39 to 0.77 and from 0.44 to 0.78, respectively. In addition to this, we
evaluated these microsatellites in 2 populations of C. acutus and C. moreletii to
assess their utility in estimating intraspecific levels of polymorphisms. These
microsatellites also showed considerable allelic variation in population level
analysis. The set of 10 microsatellite loci in our study had the potential to be
used as a tool in population and conservation genetic studies of Neotropical
crocodiles.
PMID- 25117305
TI - Development of polymorphic expressed sequence tag-single sequence repeat markers
in the common Chinese cuttlefish, Sepiella maindroni.
AB - The common Chinese cuttlefish (Sepiella maindroni) is one of the popular edible
cephalopod consumed across Asia. To facilitate the population genetic
investigation of this species, we developed fourteen polymorphic microsatellite
makers from expressed sequence tags of S. maindroni. The number of alleles at
each locus ranged from 6 to 10 with an average of 7.9 alleles per locus. The
ranges of observed and expected heterozygosity were from 0.615 to 0.962 and 0.685
to 0.888, respectively. Four loci were found deviated significantly from Hardy
Weinberg equilibrium. The polymorphism information content ranged from 0.638 to
0.833. These polymorphic microsatellite loci will be helpful for the population
genetic, genetic linkage map, and other genetic studies of S. maindroni.
PMID- 25117306
TI - Molecular identification of Amazonian stingless bees using polymerase chain
reaction single-strand conformation polymorphism.
AB - In countries containing a mega diversity of wildlife, such as Brazil, identifying
and characterizing biological diversity is a continuous process for the
scientific community, even in face of technological and scientific advances. This
activity demands initiatives for the taxonomic identification of highly diverse
groups, such as stingless bees, including molecular analysis strategies. This
type of bee is distributed in all of the Brazilian states, with the highest
species diversity being found in the State of Amazonia. However, the estimated
number of species diverges among taxonomists. These bees are considered the main
pollinators in the Amazon rainforest, in which they obtain food and shelter;
however, their persistence is constantly threatened by deforestation pressure.
Hence, it is important to classify the number and abundance of bee specie, to
measure their decline and implement meaningful, priority conservation strategies.
This study aims to maximize the implementation of more direct, economic and
successful techniques for the taxonomic identification of stingless bees.
Specifically, the genes 16S rRNA and COI from mitochondrial DNA were used as
molecular markers to differentiate 9 species of Amazonian stingless bees based on
DNA polymorphism, using the polymerase chain reaction-single-strand conformation
polymorphism technique. We registered different, exclusive SSCP haplotypes for
both genes in all species analyzed. These results demonstrate that SSCP is a
simple and cost-effective technique that is applicable to the molecular
identification of stingless bee species.
PMID- 25117307
TI - Regulatory effect of iron regulatory protein-2 on iron metabolism in lung cancer.
AB - Iron metabolism plays an important role in the pathogenesis of lung cancer. This
study aimed to investigate the effect of gene silencing of iron regulatory
protein-2 (IRP2) on mRNA and protein expression of transferrin (Tf), transferrin
receptor (TfR), and ferritin (Fn) in A549 lung cancer cells. A549 cells were
cultured and divided into a liposome control group, a liposome + oligonucleotide
(SCODN) control group, and a Lipofectamine + antisense oligonucleotide (ASODN)
group. RT-PCR and Western blotting were used to detect mRNA and protein
expression of Tf, TfR, and Fn. We found no significant change in Tf mRNA
expression among the 3 groups (P = 0.078). TfR and Fn mRNA expressions in the
ASODN group notably decreased compared to the liposome and SCODN groups (P <
0.01). IRP2 and TfR protein expressions in the ASODN group were significantly
lower than in the liposome or SCODN groups (P < 0.05), whereas no significant
change in Tf protein expression was observed between the 3 groups (P = 0.088). Fn
protein expression in the ASODN group was significantly higher than in the
liposome or SCODN group (P < 0.05). IRP2 can regulate the expression of TfR and
Fn by changing its own protein expression and thereby regulate iron metabolism.
PMID- 25117308
TI - Treatment of seawater immersion-complicated open-knee joint fracture.
AB - The current study aimed to select suitable remedies for seawater immersion
complicated open-knee joint fracture by exploring the effects of different
treatment methods. Forty adult rabbits weighing 2.20 +/- 0.25 kg were divided
equally into internal fracture fixation group (A), seawater-immersed group with
primary internal fixation (B), seawater-immersed group with secondary internal
fixation (C), and seawater-immersed group with external fixation (D), using the
random-digit table method. Open-femoral internal condylar fracture models were
established. Group A was left untreated for 2 h, whereas the other three groups
were subjected to seawater immersion for 2 h. Afterwards, groups A and B
underwent debridement and steel plate and screw internal fixation. Group C
underwent debridement and external fixation, which was followed by secondary
steel plate and screw internal fixation after the wound healed. Group D underwent
transarticular arthrodesis. Wound infection, joint functional rehabilitation, and
radiological and histopathological changes in fracture healing in each group were
assessed. The results showed that delayed internal fixation effectively reduces
the infection rate of seawater immersion-complicated open fracture and benefits
joint function rehabilitation.
PMID- 25117309
TI - Prostate stem cell antigen rs2294008 (C>T) polymorphism and bladder cancer risk:
a meta-analysis based on cases and controls.
AB - Several published articles have evaluated the association between the prostate
stem cell antigen (PSCA) rs2294008 (C>T) polymorphism and bladder cancer risk,
but the results remain inconclusive. In order to derive a more precise estimation
of the association, we performed a meta-analysis of four case-control studies
that included 9617 cases and 16,323 controls. Odds ratios (ORs) and 95%
confidence intervals (CIs) were used to assess the strength of the association.
Our meta-analysis showed that, overall, the rs2294008 (C>T) polymorphism was
associated with bladder cancer susceptibility (OR = 1.29, 95%CI = 1.20-1.40 for
TT vs CC; OR = 1.24, 95%CI = 1.16-1.31 for CT vs CC; OR = 1.25, 95%CI = 1.18-1.33
for TT/CT vs CC; OR = 1.13, 95%CI = 1.06-1.20 for TT vs CT/CC). In the stratified
analyses, the risk remained significant for studies of European populations,
Asian populations, population-based studies, and hospital-based studies. In
conclusion, the results suggest that the PSCA rs2294008 (C>T) polymorphism is a
risk factor for bladder cancer development.
PMID- 25117310
TI - Experimental strategies in performing value for cultivation and use experiments
for the tobacco crop II: dimension of the experimental network.
AB - In this study, we aimed to establish strategies for value for cultivation and use
(VCU) experiments for the tobacco crop in the southern region of Brazil with
respect to the number of environments used to assess tobacco lines. Trials of the
Virginia (18 sites) and Burley (17 sites) varietal groups were conducted in the
three states of the southern region of Brazil in the 2009-2010 crop season. The
experiment was conducted in a completely randomized block design with four
replications of 10 tobacco lines in the final stage of evaluation; the plots had
6 rows of 7 plants each, or 42 plants per plot. The cured leaf weight per hectare
(kg/ha) was obtained. To evaluate stability, the ecovalence and additive main
effects and multiplicative interaction models were adopted. In addition, joint
analyses of variance were carried out considering different site numbers by
simulating resampling. The site number ranged from 2 to 17 or 2 to 16, depending
on the varietal group, and sites were selected at random without replacement. The
process was repeated 2000 times for each number of sites. All analyses were
performed using the R software. The results are very similar for both varietal
groups. There is no advantage of using a large number of sites for VCU
experiments in the southern region of Brazil because many sites contributed
little to the interaction or did not discriminate the tobacco lines. Furthermore,
the classification of the best lines is very similar to that obtained in the
total number of evaluated sites.
PMID- 25117311
TI - Association between EGF and VEGF functional polymorphisms and sporadic colorectal
cancer in the Malaysian population.
AB - Growth factors are polypeptides that are critical for the initiation,
progression, and metastasis of cancer. Most tumor cells are capable of
synthesizing particular growth factors leading to constitutive pathway activation
in these cells through autocrine signaling. Epidermal growth factor (EGF) is a
potent mitogenic peptide that exerts direct effects on the proliferation and
differentiation of tumor cells in carcinogenesis. By contrast, vascular
endothelial growth factor (VEGF) is vital for the invasion and metastasis of
neoplasms through the formation of new blood vessels from mature endothelial
cells. In this study, we investigated the association between functional
polymorphisms of both the EGF and VEGF genes and colorectal cancer (CRC)
susceptibility. A total of 130 CRC patients and 212 healthy controls were
recruited for this case-control study. Genotyping of genetic variants was
conducted via real-time polymerase chain reaction (PCR) amplification with allele
specific TaqMan probes. None of the genotypes of the EGF +61 A>G and VEGF +936
C>T variants was significantly associated with CRC susceptibility among the
Malaysian subjects evaluated (P > 0.05). The observed frequency distributions of
the EGF +61 A>G polymorphism genotypes showed ethnic heterogeneity, which was not
the case for the VEGF +936 C>T genotypes. In conclusion, no positive correlation
between these functional polymorphisms and CRC risk was found in this Malaysian
population. Studies of the EGF and VEGF genes and CRC susceptibility are scarce,
and the results reported thus far differ from one population to another. Hence,
more replication studies are warranted before any firm conclusions can be made.
PMID- 25117312
TI - Development of eight novel microsatellite markers for Huoyan geese.
AB - In this study, we isolated microsatellite DNA from the Huoyan goose genome with
magnetic beads. As a result, 150 positive clones were identified, and 148
microsatellites were found. Among the 148 microsatellites, 69.6% were perfect,
17.6% were imperfect, and the rest were compound type (12.8%). Twenty
microsatellite primers were used to screen 90 individuals from 3 Huoyan goose
populations. Eight loci were polymorphic with a low number of alleles (2 to 4).
The observed and expected heterozygosities ranged from 0.3556 to 1 and from
0.2923 to 0.6868, respectively. All the 8 polymorphic loci were in Hardy-Weinberg
equilibrium. These molecular markers will be useful for future studies on
population genetic structure and conservation genetics in Huoyan geese.
PMID- 25117313
TI - Comparison of methods for estimates of molecular genetic diversity in genus
Croton: influence of coefficients, clustering strategies and data projection.
AB - We investigated 10 similarity (and disimilarity) coefficients in a set of 40 wild
genotypes of Croton linearifolius subjected to analyses using hierarchical
grouping methods, grouping methods by optimization and data projection in two
dimensional space. Genotypes were characterized by analyzing DNA polymorphism
with the use of 15 ISSR and 12 RAPD markers. The distance measurements were
compared by the Spearman correlation test, projection in two-dimensional space
and grouping efficiency evaluation. The Spearman correlation coefficients between
the 10 coefficients evaluated were significant (P < 0.001) and indicated
significant changes in genotype ranking due to type of coefficient used (0.76 <=
rs <= 1). Wide variation was also observed in the efficiency of clustering
methods, where the unweighted pair group method with arithmetic mean was the most
suitable (0.3 <= D <= 1.5 ; 0.41 <= rc <= 0.77; 5.99 <= S <= 12.61). Projection
efficiencies in two-dimensional space showed high-stress values (65 < S < 89%).
Similar to the results observed for hierarchical clustering methods and for
projection in two-dimensional space, the formation of groups with grouping
methods by optimization showed variations when using different coefficients. We
believe that the results confirm the influence of coefficients in studies of
genetic diversity, showing the need to use criteria and standards for selecting
appropriate methods for genetic studies of the genus Croton.
PMID- 25117314
TI - Implications of microRNA-197 downregulated expression in esophageal cancer with
poor prognosis.
AB - The aim of this study was to investigate the significance of the microRNA miR-197
expression level in relation to clinicopathological factors and prognoses of
esophageal cancer (EC). MicroRNA was extracted using the Taqman((r)) MicroRNA
Assay from 46 EC patients at the same tumor node metastasis (TNM) stage, but with
different prognoses, who underwent surgery. Paracancerous normal tissues were
used as controls. The correlation between miR-197 expression and
clinicopathologic features was analyzed, and the significance of miR-197 as a
prognostic factor and its relationship with survival was determined. miR-197
expression was lower in patients with poor prognosis than in those with good
prognosis (P < 0.05). Kaplan-Meier analysis results showed that the miR-197
expression level is significantly correlated with survival time (P = 0.030), and
that patients with higher expression of miR-197 had longer survival times. Cox
multi-factor model analysis showed that patient prognosis (P = 0.001), tumor
length (P = 0.010) and expression (P = 0.042), and survival time were
significantly correlated, with corresponding risks of 9.183, 2.318, and 1.925,
respectively. This study supports a role of miR-197 as an anti-oncogene and a
biomarker for EC and its relationship with other prognostic factors and survival.
PMID- 25117315
TI - A potential protective role for thiamine in glucose-driven oxidative stress.
AB - The relationship between glucose repression and the oxidative stress response was
investigated in Schizosaccharomyces pombe wild type cells (972h(-)) and glucose
repression resistant mutant type cells (ird11). We aimed to reveal the mechanism
of simultaneous resistance to glucose repression and oxidative stress in ird11
mutants. Compared to the wild type, the expression of the sty1 gene was not
altered in the ird11 mutant under normal growth conditions, but decreased after
exposure to H2O2. This effect was clearly explained by the immunoblotting
results, which showed elevated levels of a much more stable phosphorylated form
of Sty1 mitogen-activated protein kinase in the ird11 mutant. Increased ght3 gene
expression levels were also found, which may play a role in protecting the ird11
mutant from the deleterious effects of oxidative stress. In addition, decreased
expression levels of glycolytic enzyme enolase- and thiamine synthesis/transport
related genes were detected. This might have resulted from the flux redirection
toward mitochondrial respiration, which would enhance NADPH generation to prevent
the high reactive oxygen species accumulation that is generated by respiration.
Some evidence supported a flux shift toward fermentation as well as respiration.
We conclude that a defect in the glucose-sensing signaling pathway in ird11
mutants likely causes erroneous low glucose-sensing signaling and high ATP
production. This most likely occurs because high glucose availability in the
medium induces an impairment in the respiratory chain and fermentation balance in
these cells, which might explain the glucose repression and oxidative stress
resistance in ird11 compared to the wild type.
PMID- 25117316
TI - Diagnosis of lymph node micrometastasis at the pN0 stage of lung adenocarcinoma
using a combination of markers.
AB - This study aimed to detect micrometastatic tumor cells in the lymph nodes of
patients with pN0 lung adenocarcinoma using a combination of thyroid
transcription factor-1 (TTF-1) expression and cytokeratin 7 (CK7) expression and
to investigate the association of lymph node micrometastasis with the
clinicopathological characteristics of patients with lung adenocarcinoma. A total
of 54 patients with pN0 lung adenocarcinoma and whose primary tumors were
positive for both TTF-1 and CK7 expression were included in this study. In total,
893 lymph nodes were obtained from these 54 patients and were analyzed for
micrometastasis by immunohistochemical staining with anti-CK7 and anti-TTF-1
antibodies. CK7- and TTF-1-positive cells were found in the lymph nodes of 9
(16.7%) of 54 patients, and 21 (2.4%) of 893 lymph nodes exhibited positivity for
these factors. No cells positive for both CK7 and TTF-1 were detected in the 5
lymph nodes obtained from patients with benign lung tumors. Lymph node
micrometastasis was found to be associated with the differentiation grade and
primary tumor position (P < 0.05). The detection of lymph node micrometastasis by
a combination of CK7 and TTF-1 immunohistochemical staining provides a more
accurate assessment of tumor staging for pN0 lung adenocarcinoma.
PMID- 25117317
TI - Development and characterization of microsatellite loci for Tabebuia cassinoides
(Bignoniaceae).
AB - Tabebuia cassinoides (Lam.) DC., popularly known as caxeta, is a tree species
that belongs to the plant family Bignoniaceae. This species is endemic to the
Brazilian Atlantic Forest and is widely exploited commercially. To date, little
is known about its genetic structure, preventing the establishment of adequate
management plans for this taxon. The objective of this study was to construct a
microsatellite-enriched genomic library for T. cassinoides to select polymorphic
loci, and standardize polymerase chain reaction amplification conditions. Of the
15 loci examined, 5 were polymorphic. The number of alleles per locus ranged from
2 to 8, with a mean of 4.4. The microsatellite loci described here represent the
basis for detailed population genetic studies of this species, which will greatly
contribute for the development of better conservation strategies for this taxon.
PMID- 25117318
TI - Effects of phenylalanine on reproductive performance and teratogenesis in mice.
AB - We evaluated the effects of phenylalanine on reproductive performance and
teratogenesis in mice, as well as we assessed its protective effect in mice
treated with an acute dose of cyclophosphamide. Animals were divided into 6
experimental groups (females N = 15/group, males N = 5/group): G1, the negative
control group, phosphate-buffered saline; G2, the positive control group, 35 mg
cyclophosphamide/kg body weight (b.w.); G3 and G4 received phenylalanine at doses
of 150 and 300 mg/ kg b.w., respectively; G5 and G6 received phenylalanine at
doses of 150 and 300 mg/kg b.w. co-administered with cyclophosphamide at a dose
of 35 mg/kg b.w., respectively. Pregnant mice received phenylalanine from 8-12
days of pregnancy and cyclophosphamide on the 10th day of treatment or the
respective vehicles. In animals treated with cyclophosphamide, offspring fetal
weight significantly decreased. The G5 and G6 groups, which received
cyclophosphamide co-administered with phenylalanine, showed a smaller reduction
in weight. Based on this analysis, the offspring from groups G2, G5, and G6
showed low weight due to pregnancy age. Moreover, at the doses used,
phenylalanine did not interfere with embryo-fetal development. However, further
studies are necessary to increase the understanding of the effects of
phenylalanine on mouse reproductive performance and teratogenesis.
PMID- 25117319
TI - Identification of complete linkage disequilibrium in the DSG4 gene and its
association with wool length and crimp in Chinese indigenous sheep.
AB - The desmoglein 4 (DSG4) gene is a potential candidate in the search for genes
that may affect wool traits, because of its function. This study aimed to screen
for polymorphisms in partial exon 16 and 3?UTR of the sheep desmoglein 4 DSG4
gene, and to test its possible association with wool length and crimp associated
with fur. Overall, 326 sheep were scanned via single-strand conformational
polymorphism assay, through three pairs of primers. The breeds included Tan, Han,
and TanxHan from China, Polled Dorset from Australia, and Suffolk from Britain
genotypes AA, BB, and AB for primer2 and genotypes DD, EE, and DE for primer3
were detected in native breeds. Six SNPs and 3-bp insertion/deletions were found
in exon 16, of which 4 lead to amino acid substitutions. In addition, 1 SNP was
found in 3?UTR. The DSG4 genotype was found to be strongly associated with all
wool traits that were considered in this study (P < 0.01). Sheep with the
genotype MM had a higher least square mean compared to sheep with the genotype WW
or WM with respect to birth scapular wool length (P < 0.01), crimp number of
birth scapular wool crimp (P < 0.01), crimp number of weaning scapular wool crimp
(P < 0.01), and crimp number of weaning rump wool crimp (P < 0.01, P < 0.05). In
conclusion, our study is the first to demonstrate that the DSG4 gene may be a
candidate, or major gene, which influences important wool traits.
PMID- 25117320
TI - Soybean rust resistance sources and inheritance in the common bean (Phaseolus
vulgaris L.).
AB - Soybean rust (SBR), caused by the fungus Phakopsora pachyrhizi, has been reported
in common bean (Phaseolus vulgaris L.) cultivars and elite lines that were
infected under controlled and natural field conditions in South Africa, the
United States, Argentina, and Brazil. Although SBR is currently not a top
priority problem for the common bean crop, many bean breeders are concerned about
this disease because of the high severity and virulence diversity of P.
pachyrhizi and its broad host range. In this study, a set of 44 P. vulgaris
genotypes were tested for resistance to P. pachyrhizi; these genotypes included
resistance sources to several fungal common bean diseases, carioca-, black- and
red-seeded Brazilian cultivars, and elite lines that were developed by the main
common bean breeding programs in Brazil. Twenty-four SBR resistance sources were
identified. They presented the reddish-brown (RB) lesion type, characterizing
resistance reactions. In addition to the RB lesion type, the PI181996 line
presented the lowest disease severity mean score, considering its associated
standard error value. For this reason, it was crossed with susceptible lines to
study the inheritance of resistance. The results support the hypothesis that
resistance to SBR in PI181996 is monogenic and dominant. We propose that this SBR
resistance gene, the first to be identified and characterized in common bean,
might be designated as Pkp-1.
PMID- 25117321
TI - CYP1A2 polymorphism in Chinese patients with acute liver injury induced by
Polygonum multiflorum.
AB - The objective of this study was to evaluate the genotype and allelic frequencies
of CYP1A2 in Chinese patients with acute liver injury induced by Polygonum
multiflorum. We examined the clinical mechanism of acute liver injury induced by
P. multiflorum. According to the diagnostic criteria for drug-induced liver
injury (DILI), 43 cases of P. multiflorum-induced liver injury admitted to the
First Affiliated Hospital, Zhejiang University were identified between January
2008 and December 2012. An additional 43 control subjects were also chosen.
Several alleles, including 1C, 1F, 2, 7, 9, and 11 of CYP1A2 were amplified from
genomic DNA and sequenced. We used the chi-square test to determine whether
CYP1A2 allele polymorphisms are associated with acute liver injury induced by P.
multiflorum. The frequency of the CYP1A2 1C allele was 46.5% in P. multiflorum
induced DILI patients, which was significantly different from the frequency of
27.9% observed in healthy subjects. The frequency of the CYP1A2 1F allele was
63.9% in P. multiflorum-induced DILI patients, compared to 57.0% in healthy
controls; the difference was not significant. The allelic frequencies of CYP1A2
2, CYP1A2 7, CYP1A2 9, and CYP1A2 11 were too low to be detected. The frequency
of the CYP1A2 1C mutation in Chinese patients with P. multiflorum-induced acute
liver injury differed from that in healthy Chinese people, indicating that CYP1A2
1C is probably related to metabolism of P. multiflorum, which is followed by
acute liver injury.
PMID- 25117322
TI - Bovine papillomavirus in beef cattle: first description of BPV-12 and putative
type BAPV8 in Brazil.
AB - Bovine papillomavirus (BPV) is an oncogenic virus associated with benign and
malignant lesions, which result in notable economic losses. Peripheral blood
samples and cutaneous papillomas were obtained from four adult beef cattle. Viral
molecular identification was performed using specific primers for BPV-1, -2 and
4 in blood diagnosis and FAP59/FAP64 for skin papillomas. Histopathologic
examination was done as a complementary and differential diagnosis. The fragments
were purified, sequenced, and compared using BLASTn. The blood diagnosis showed
the presence of BPV-2 and the analysis of cutaneous papillomas showed the
presence of BPV-4, a new putative virus type BAPV8, and BPV-12, revealing for the
first time the presence of BPV-12 and the putative type BAPV8 in beef cattle in
Brazil. The sequences were deposited in the GenBank. Histopathology revealed
acanthosis, hyperkeratosis, and koilocytosis in all samples analyzed. The
presence of BAPV8 and BPV-12 in Brazil emphasizes the ubiquitous dissemination of
BPVs in the herds of Brazil.
PMID- 25117323
TI - Multiple nevoid basal cell carcinoma syndrome associated with congenital orbital
teratoma, caused by a PTCH1 frameshift mutation.
AB - Gorlin-Goltz syndrome, or nevoid basal cell carcinoma syndrome (NBCCS), is a rare
autosomal dominant disorder caused by mutations in the PTCH1 gene and shows a
high level of penetrance and variable expressivity. The syndrome is characterized
by developmental abnormalities or neoplasms and is diagnosed with 2 major
criteria, or with 1 major and 2 minor criteria. Here, we report a new clinical
manifestation associated with this syndrome in a boy affected by NBCCS who had
congenital orbital teratoma at birth. Later, at the age of 15 years, he presented
with 4 major and 4 minor criteria of NBCCS, including multiple basal cell
carcinoma and 2 odontogenic keratocysts of the jaw, both confirmed by histology,
more than 5 palmar pits, calcification of the cerebral falx, extensive meningeal
calcifications, macrocephaly, hypertelorism, frontal bosses, and kyphoscoliosis.
PTCH1 mutation analysis revealed the heterozygous germline mutation c.290dupA.
This mutation generated a frameshift within exon 2 and an early premature stop
codon (p.Asn97LysfsX43), predicting a truncated protein with complete loss of
function. Identification of this mutation is useful for genetic counseling.
Although the clinical symptoms are well-known, our case contributes to the
understanding of phenotypic variability in NBCCS, highlighting that PTCH1
mutations cannot be used for predicting disease burden and reinforces the need of
a multidisciplinary team in the diagnosis, treatment, and follow-up of NBCCS
patients.
PMID- 25117324
TI - Agronomic performance of arabica coffee genotypes in northwest Rio de Janeiro
State.
AB - Considering the productive potential of arabica coffee in the Rio de Janeiro
State and the shortage of breeding programs for this species in the state, this
study aimed to evaluate the vegetative and productive characteristics of 25
arabica coffee genotypes to indicate 1 or more varieties for the northwest Rio de
Janeiro region. The experiment was in Varre e Sai, RJ, Brazil, and plants were
planted in 2007 with a spacing of 2.5 x 0.8 m. Five plots were used, consisting
of 8 plants per plot to measure vegetative growth, height, stem diameter, and
plagiotropic branch number characteristics and productivity in the biennia
2009/2010 and 2011/2012. The classification by sieve was performed at harvest in
2011. The variables were subjected to analysis of variance and means grouped by
the Scott Knott test at 5% probability, and the productivity was subjected to
joint analysis of variance. Pearson's correlation coefficients between growth and
productivity variables were estimated. The best genotypes were Catucai Amarelo 2
SL, Catigua MG 02, Acaua, Palma II, Sabia 398, IPR 103, IPR 100, Catucai Amarelo
24/137, and Catucai Amarelo 20/15.
PMID- 25117325
TI - Construction and identification of pIRES2-NGF-VEGF165 bicistronic eukaryotic
expression vector.
AB - We used a simple and efficient method to construct the bicistronic eukaryotic
expression vector pIRES2-NGF-VEGF165. The nerve growth factor (NGF) gene was
obtained from the genomic DNA of human peripheral blood mononuclear cells by
polymerase chain reaction. The NGF cDNA fragment was inserted into the multiple
cloning sites of the pIRES2-EGFP vector to generate the bicistronic eukaryotic
expression plasmid pIRES2-NGF-EGFP. The vascular endothelial growth factor 165
(VEGF165) gene was obtained from the pIRES2-VEGF165-EGFP plasmid by polymerase
chain reaction. Next, the VEGF165 cDNA fragment was cloned into pIRES2-NGF-EGFP
in place of enhanced green fluorescent protein creating the plasmid pIRES2-NGF
VEGF165. pIRES2-NGF-VEGF165 was transfected into HEK293 cells and reverse
transcription-polymerase chain reaction and Western blot analysis were used to
test the co-expression of double genes. The NGF and VEGF165 genes were cloned and
the DNA was sequenced, which revealed that NGF and VEGF165 were consistent with
the sequence recorded in GenBank. Restriction analysis showed that the NGF and
VEGF165 genes were inserted into the expression vector pIRES2-EGFP. Transfection
of pIRES2-NGF-VEGF165 into HEK293 cells resulted in expression of the double gene
at the mRNA and protein levels. The NGF and VEGF165 coexpression plasmid provides
a novel expression system, enabling further study of the functions of the NGF and
VEGF165 genes.
PMID- 25117326
TI - Bias toward a 1:1 ratio in primer-introduced restriction analysis PCR: mechanism
and minimization.
AB - Primer-introduced restriction analysis is widely used in molecular genetics.
However, several studies have reported inconsistent data regarding sequencing,
mainly among heterozygous samples. This discrepancy may be related to the bias
towards a 1:1 ratio typically observed in heterozygous digestion products. In
this study, we investigated the mechanism and minimization of this observed bias.
Three mismatched polymerase chain reaction (PCR) models were analyzed by testing
different PCR conditions and reaction mixtures. For EPHX1 gene rs1051740 single
nucleotide polymorphism PCR, DNA concentration, denaturation and elongation time,
annealing temperature, and cycle number significantly influenced product ratios.
For SERPINA1 gene PIMmalton deletion (DeltaPhe52) and CHRNA3 gene rs1051730
single-nucleotide polymorphism PCRs, significant bias fluctuations were observed
only for the annealing temperature and cycle number conditions. The relevance of
these results to the amplification efficiency parameter is discussed. Rather than
reducing the observed bias, our data provide evidence of a counterbalance for
preferential amplification, depending on cycle number, annealing temperature, and
amplification efficiency alteration. Our results are relevant for application to
primer-introduced restriction analysis PCR assays.
PMID- 25117327
TI - Pulmonary hypertension in patients with stage 1-3 chronic kidney disease.
AB - Pulmonary hypertension (PH) secondary to chronic kidney disease (CKD) is common,
but in stages 1-3 CKD patients, it remains unclear. We sought to evaluate the
prevalence of PH and elucidate the possible pathogenesis in Chinese patients with
early stage kidney disease. Doppler-estimated pulmonary systolic artery pressure
(PASP) was measured in 101 CKD patients with glomerular filtration rate (GFR) >=
60 mL/min/1.73 m(2) and 27 CKD patients with GFR < 60 mL/min/1.73 m(2).
Echocardiographic parameters, plasma brain natriuretic peptide (BNP), and
baseline characteristics of patients were recorded. PH was defined as a PASP >=
35 mmHg. PH prevalence was 23.76% (24/101) in GFR >= 60 mL/min/1.73 m(2) group
and 48.15% (13/27) in GFR < 60 mL/min/1.73 m(2) group, P < 0.05. Mean lnBNP was
4.93 +/- 1.60 pg/mL in 37 cases with PH and 2.89 +/- 1.29 pg/mL in those without,
P < 0.01. Left atrial diameter (LA) showed deviation between patients with (43.94
+/- 5.81 mm) and without PH (37.76 +/- 7.48 mm), P < 0.01. GFR declined
significantly in PH group (44.10 +/- 22.90 mL/min/1.73 m(2)) compared to non-PH
group (75.59 +/- 31.62 mL/min/1.73 m(2)), P < 0.01. lnBNP, LA and GFR were
independent determinants (r = 0.651, 0.595, -0.488, P < 0.01) of PASP. PH is
prevalent among stage 1-3 CKD patients in China. Doppler-estimated PASP is
strongly associated with lnBNP, enlarged LA and GFR. Monitoring PASP, plasma BNP
and evaluation renal function may help to detect and prevent severe PH in CKD.
PMID- 25117328
TI - Outbreaks and genetic diversity of Francisella noatunensis subsp orientalis
isolated from farm-raised Nile tilapia (Oreochromis niloticus) in Brazil.
AB - Francisella noatunensis subsp orientalis (FNO) is an emerging pathogen of warm
water tilapia in a number of different countries. The disease caused by this
bacterium in fish is characterized by a systemic granulomatous infection that
causes high mortality rates during outbreaks. FNO has been previously described
in Asia, Europe, and Central and North America. Its occurrence in South America
has never been described. Since 2012, outbreaks of a granulomatous disease have
been recorded in cage farms of Nile tilapia (Oreochromis niloticus L.) in Brazil.
The current study aimed to identify the etiologic agent of recent francisellosis
outbreaks at Brazilian tilapia farms, and to characterize the genetic diversity
of the pathogen from farms with distinct geographic origins and without
epidemiological connections. Bacteriological analysis of 44 diseased Nile tilapia
collected from five cage farms in Brazil was performed during 2012 and 2013. The
farms were in different locations and had no recent history of animal or
biological material transport between each other. Sixty-two FNO isolates were
identified on the basis of FNO-specific qPCR. The main predisposing factors for
the occurrence of outbreaks on Brazilian farms were lower water temperature (<22
degrees C) and life stage of fish, affecting mainly fry, fingerlings and young
adults (live weight <100 g). The genetic diversity of the Brazilian FNO isolates
was evaluated using repetitive extragenic palindromic-PCR. The isolates from
different origins were shown to be clonally related. This is the first report of
the occurrence and genetic diversity of FNO in South America.
PMID- 25117329
TI - Pharmacogenomics: accessing important alleles by imputation from commercial
genome-wide SNP arrays.
AB - Personalized medicine is becoming a medical reality, as important genotype
phenotype relationships are being unraveled. The availability of pharmacogenomic
data is a key element of individualized care. In this study, we explored genotype
imputation as a means to infer important pharmacogenomic alleles from a regular
commercially available genome-wide SNP array. Using these arrays as a starting
point can reduce testing costs, increasing access to these pharmacogenomic data
and still retain a larger amount of genome-wide information. IMPUTE2 and MaCH
Admix were used to perform genotype imputation with a dense reference panel from
1000 Genomes data. We were able to correctly infer genotypes for the warfarin
related loci VKORC1 and CYP2C9 alleles 2, 3, 5, and 11 and also clopidogrel
related CYP2C19 alleles 2 and 17 for a small sample of Brazilian individuals, as
well as for HapMap samples. The success of an imputation approach in admixed
samples using publicly available reference panels can encourage further
imputation initiatives in those populations.
PMID- 25117330
TI - Ranking of Nellore animals in cattle championships: genetic parameters and
correlations with production traits.
AB - Records of 17,141 Nellore cattle participating in cattle championships, born from
1994-2009, were used to estimate genetic parameters between animal rank in cattle
championships, evaluated from weaning to 36 months of age as repeated traits, and
growth, fertility, and carcass traits, evaluated at 365 days of age as single
traits. Two traits were defined for animal rank in cattle championships: value 1
was attributed to animals ranked from 1st to 3rd place within the age category,
and value 0 was assigned to the remaining animals (TOP3). Value 1 was attributed
to animals ranked from 1st to 5th place within the age category and value 0 was
assigned to the remaining animals (TOP5). The (co)variance components were
estimated based on Bayesian inference under a 2-trait threshold-linear animal
model. The posterior means of heritability estimated for TOP3 and TOP5 were 0.182
+/- 0.010 and 0.260 +/- 0.012, respectively, and their repeatabilities were 0.341
+/- 0.007 and 0.400 +/- 0.007, respectively. High-ranking animals generally
presented higher breeding values for body weight, height, body length, and heart
girth. The phenotypic correlations indicate that judges of cattle championships
primarily rank animals based on weight and heart girth.
PMID- 25117331
TI - HIF1A gene Pro582Ser polymorphism and susceptibility to digestive tract cancers:
a meta-analysis of case-control studies.
AB - Many existing studies have demonstrated that common polymorphisms in the hypoxia
inducible factor-1alpha (HIF-1A) may contribute to the development of digestive
tract cancers, but individually published studies showed inconclusive results.
This meta-analysis aimed to derive a precise estimation of the relationships
between HIF1A Pro582Ser polymorphism and the risk of digestive tract cancers. We
searched CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane
Library, and CBM databases from inception through May 1, 2013. Meta-analysis was
performed using the STATA 12.0 software. We assessed 6 case-control studies that
included a total of 911 digestive tract cancer patients and 2774 healthy
controls. Our meta-analysis indicated that HIF1A Pro582Ser polymorphism was
associated with an increased risk of digestive tract cancer. Subgroup analysis by
ethnicity suggested that HIF1A Pro582Ser polymorphism might increase an
individual's susceptibility to digestive tract cancer in Asian populations.
However, similar association was not observed in Caucasian populations. In
conclusion, our findings suggest that HIF1A Pro582Ser polymorphism may contribute
to the risk of digestive tract cancers, especially in Asian populations.
PMID- 25117332
TI - Fibroin protein/chitosan scaffolds and bone marrow mesenchymal stem cells culture
in vitro.
AB - A previous experiment demonstrated that fibroin protein and chitosan mixed in
proper proportion presented good physical and chemical properties and biological
characteristics, which can make up for their respective disadvantages. To observe
the growth of bone marrow mesenchymal stem cells (BMSCs) on these fibroin
protein/chitosan 3D scaffolds, induced rabbit BMSCs were seeded on fibroin
protein/chitosan scaffolds. The cell adhesion rate was measured, and cell growth
was observed under an inverted microscope and a scanning electron microscope. The
cell adhesion rate increased with time. The inverted microscope observations
showed that the cells on fibroin protein/chitosan scaffolds could not be seen
clearly. As time passed, the number of cells around the stent increased and some
cells stretched inside the scaffolds. Electron microscopy showed active cell
growth and normal proliferation, and the granular and filamentous matrix
substances could be seen around cells. The microfilaments of cell and scaffold
materials were tightly connected. The cells not only grew on the surface of the
adherent material, but also stretched inside of the materials. These results
indicated that the fibroin protein/ chitosan mixed scaffolds have good
biocompatibility.
PMID- 25117333
TI - Association study of plasma NT-proBNP levels and severity of acute coronary
syndrome.
AB - The aim of this study was to investigate the N-terminal brain natriuretic peptide
precursor (NT-proBNP) levels in the peripheral blood of patients with acute
coronary syndrome (ACS) and to provide the basis for its application in the early
diagnosis of ACS. A total of 440 patients admitted to the hospital for
examination and treatment were enrolled, including 330 patients with ACS and 110
cases in the control group. Routine blood examination and determination of NT
proBNP in all subjects were conducted immediately at the time of admission to
analyze the difference in plasma NT-proBNP between the two groups. The plasma NT
proBNP levels in ACS were significantly higher (P < 0.01) and were associated
with the severity of coronary lesions. The present study indicated that the
plasma NT-proBNP level in ACS patients is significantly increased and has a
potential value in the early diagnosis of ACS.
PMID- 25117334
TI - Alteration of coenzyme specificity of malate dehydrogenase from Streptomyces
coelicolor A3(2) by site-directed mutagenesis.
AB - We describe here for the first time the alteration of coenzyme specificity of
malate dehydrogenase (MDH) from Streptomyces coelicolor A3(2) (ScMDH). In the
present study, we replaced four amino acid residues in the Rossmann fold (betaB
alphaC) region of NADH-dependent ScMDH by site-directed mutagenesis with those of
NADPH-dependent MDH (Glu42Gly, Ile43Ser, Pro45Arg, and Ala46Ser). The coenzyme
specificity of the mutant enzyme (ScMDH-T4) was examined. Coenzyme specificity of
ScMDH-T4 was shifted 2231.3-fold toward NADPH using kcat/Km(coenzyme) as the
measurement of coenzyme specificity. Accordingly, the effect of the replacements
on coenzyme specificity is discussed. Our work provides further insight into the
coenzyme specificity of ScMDH.
PMID- 25117335
TI - Influence of hepatic ischemia-reperfusion on postoperative spatial cognitive
function in mice.
AB - The aim of this study was to investigate the effects of partial hepatic
ischemia/reperfusion (I/R) on postoperative cognitive function in mice. One
hundred Kunming mice were randomized into control group (N = 20), sham group (N =
20) and I/R group (N = 60), which was equally divided into 3 subgroups according
to the ischemia time (20, 30 and 40 min). Half of the mice in each group
underwent a passive avoidance test on the 4th day, and the other underwent the
test on the 18th day, which lasted for 6 days before euthanasia for analysis of
brain pathology and immunohistochemistry for ChAT. The passive avoidance test
showed that there was no significance in the incubation period and number of
errors between the control and sham group, but there was a longer incubation
period and more errors in the I/R group than control group; at G2, there was no
significance between all groups. Hematoxylin-eosin staining of the hippocampus
showed that at G1, there was no obvious change in hippocampal neurons in
structure and arrangement except for IR/40 min; at G2, there was no significance
between all groups. Immunohistochemistry of hippocampus for ChAT showed the
following: at G1, there was no significance in average optical density of CA3
area between control and sham group, but optical density was significantly lower
in I/R groups with I/R 40 min showing the lowest; at G2, there was no
significance between all groups. Pentobarbital has no effect on cognitive
function, but hepatic partial ischemia and reperfusion injury does and could
become worse over time.
PMID- 25117336
TI - Analysis of genetic relationships and identification of lily cultivars based on
inter-simple sequence repeat markers.
AB - Inter-simple sequence repeat (ISSR) markers were used to discriminate 62 lily
cultivars of 5 hybrid series. Eight ISSR primers generated 104 bands in total,
which all showed 100% polymorphism, and an average of 13 bands were amplified by
each primer. Two software packages, POPGENE 1.32 and NTSYSpc 2.1, were used to
analyze the data matrix. Our results showed that the observed number of alleles
(NA), effective number of alleles (NE), Nei's genetic diversity (H), and
Shannon's information index (I) were 1.9630, 1.4179, 0.2606, and 0.4080,
respectively. The highest genetic similarity (0.9601) was observed between the
Oriental x Trumpet and Oriental lilies, which indicated that the two hybrids had
a close genetic relationship. An unweighted pair-group method with arithmetic
means dendrogram showed that the 62 lily cultivars clustered into two discrete
groups. The first group included the Oriental and OT cultivars, while the
Asiatic, LA, and Longiflorum lilies were placed in the second cluster. The
distribution of individuals in the principal component analysis was consistent
with the clustering of the dendrogram. Fingerprints of all lily cultivars built
from 8 primers could be separated completely. This study confirmed the effect and
efficiency of ISSR identification in lily cultivars.
PMID- 25117337
TI - Optimization of chloroplast microsatellite PCR conditions and primer screening
for endangered Rheum officinale, Rheum palmatum, and Rheum tanguticum.
AB - Chloroplast microsatellite primers were developed in order to provide more
population genetic information of endangered Rheum officinale, R. palmatum, and
R. tanguticum for conservation. The dried roots and rhizomes of these plants are
important in traditional Chinese medicine. The results showed that the optimum
concentrations of Mg(2+), Taq DNA polymerase, dNTPs, template DNA, and primers in
a 25-MUL reaction system were 2.0 mM, 1.0 U, 0.10 mM, 20 ng, and 0.8 MUM,
respectively. Fourteen of 53 primer combinations were chosen for their high
clarity and repetition in three species, and their annealing temperatures ranged
from 56 to 58 degrees C. These primers and the optimized polymerase chain
reaction system may provide a tool for understanding the demography and genetic
variation of these endangered plants.
PMID- 25117339
TI - Sequence analysis of the PIP5K locus in Eimeria maxima provides further evidence
for eimerian genome plasticity and segmental organization.
AB - Commercial flocks infected by Eimeria species parasites, including Eimeria
maxima, have an increased risk of developing clinical or subclinical coccidiosis;
an intestinal enteritis associated with increased mortality rates in poultry.
Currently, infection control is largely based on chemotherapy or live vaccines;
however, drug resistance is common and vaccines are relatively expensive. The
development of new cost-effective intervention measures will benefit from
unraveling the complex genetic mechanisms that underlie host-parasite
interactions, including the identification and characterization of genes encoding
proteins such as phosphatidylinositol 4-phosphate 5-kinase (PIP5K). We previously
identified a PIP5K coding sequence within the E. maxima genome. In this study, we
analyzed two bacterial artificial chromosome clones presenting a ~145-kb E.
maxima (Weybridge strain) genomic region spanning the PIP5K gene locus. Sequence
analysis revealed that ~95% of the simple sequence repeats detected were located
within regions comparable to the previously described feature-rich segments of
the Eimeria tenella genome. Comparative sequence analysis with the orthologous E.
maxima (Houghton strain) region revealed a moderate level of conserved synteny.
Unique segmental organizations and telomere-like repeats were also observed in
both genomes. A number of incomplete transposable elements were detected and
further scrutiny of these elements in both orthologous segments revealed
interesting nesting events, which may play a role in facilitating genome
plasticity in E. maxima. The current analysis provides more detailed information
about the genome organization of E. maxima and may help to reveal genotypic
differences that are important for expression of traits related to pathogenicity
and virulence.
PMID- 25117338
TI - Effects of acrylonitrile on the pathological morphology and apoptosis of neurons
in rats.
AB - This study aimed to evaluate the effects of acrylonitrile (ACN) on neuronal
morphology and apoptosis in rats. An ACN solution was administered to Wistar rats
by gavage at doses of 0, 5, 10, or 20 mg/kg, 5 days a week for 13 weeks. The
morphology of neurons and the presence of apoptosis was examined by light and
electron microscope, DNA electrophoresis, immunohistochemistry, and terminal
deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Significant
vacuolation and the widening of the interspaces around blood vessels were
observed in the groups that received the highest dose. Disordered myelin sheaths,
malformed neuronal nuclei, and chromatin condensation at the periphery of the
nucleus that formed crescents were also observed in the treated rats. The number
of apoptotic neurons was significantly decreased (P < 0.05) in the treated groups
(5 mg/kg group: 1.5 +/- 1.22 apoptotic neurons/slide; 10 mg/kg group: 2.5 +/-
1.05 apoptotic neurons/slide; 20 mg/kg group: 2.34 +/- 1.21 apoptotic
neurons/slide) compared to the control group (4.5 +/- 1.52 apoptotic
neurons/slide). The number of Bcl-2-positive neurons and the levels of staining
were increased in the treated rats compared to those of the control group. These
results suggested that ACN may induce serious morphological changes in rat
neurons and inhibit neuronal apoptosis in rats.
PMID- 25117340
TI - Evaluation of genetic similarity between accessions of Pityrocarpa moniliformis
(angico-de-bezerro) using RAPD markers.
AB - Pityrocarpa moniliformis (Benth.) Luckow and Jobson, commonly known as angico-de
bezerro, is a forage legume that occurs naturally in the Caatinga of northeastern
Brazil. This fast growing, vigorous, melliferous tree is well adapted to arid
terrains and its branches and leaves possess high nutritional value. However, the
scarcity of information regarding genetic variability within the species limits
its possible exploitation as an animal forage. The aim of the study was to
evaluate the genetic similarities of ten accessions of P. moniliformis available
in the active germplasm collection of Embrapa Meio-Norte, using the RAPD markers
to select those most suitable for cultivation and/or plant breeding. Polymerase
chain reaction using ten selected RAPD primers generated 110 amplified loci, 106
(96.4%) of which were polymorphic. Primers A10 and M06 produced the largest
number of polymorphic loci (18 and 13 bands, respectively), while primers B18 and
K15 generated the smallest number (7 bands each). The dendrogram, constructed
using the Jaccard coefficients and considering a cut-off point of 0.41 allowed
the separation of the ten accessions into four genotypic groups. The highest
genetic similarity coefficient (0.56) was observed between group I accessions
BGFAB6 and BGFAB9 and BGFAB 7 and BGFAB 8, while the lowest coefficient (0.11)
was observed between accessions BGFAB3 (group IV) and BGFAB10 (group III). The
results revealed that genetic variability is present in the accessions of P.
moniliformis.
PMID- 25117341
TI - RAPD analysis of the genetic diversity among accessions of Fabaceous forages
(Poincianella spp) from the Caatinga.
AB - Among members of the Fabaceae family, native to the Brazilian Caatinga, the
species Poincianella pyramidalis and P. bracteosa exhibit particular potential as
forage for cattle, sheep and goats. With the aim of establishing genetic
relationships within Poincianella, random amplified polymorphic DNA analysis was
performed on eight accessions of P. pyramidalis and two accessions of P.
bracteosa, originating from the semiarid zone of the state of Piaui, northeastern
Brazil, and present in the germplasm bank of Embrapa Meio Norte (Teresina, Piaui,
Brazil). Amplification reactions using 11 selected arbitrary sequence primers
generated 167 fragments with an overall polymorphism of 70.38%. Five monomorphic
loci were generated exclusively in P. pyramidalis accessions, while three unique
monomorphic loci were associated with P. bracteosa, and these represented
potential species-specific markers. The similarity coefficients between
Poincianella accessions were low (mean value 0.59) but with a wide variation
(range 0.443 to 0.748). The similarity matrix and the dendrogram constructed
using the unweighted pair group method allowed the separation of Poincianella
accessions into two major clusters represented by the two distinct species, while
the accessions of P. pyramidalis could be separated further into three subgroups.
The high level of genetic diversity detected in the genus Poincianella could be
used in future breeding programs to produce enhanced cultivars, although the
variability could be better exploited if more specimens were collected from other
locations within the semiarid region of northeastern Brazil.
PMID- 25117342
TI - Genetic parameters for earnings in Quarter Horse.
AB - In this study, we estimated the heritability (h(2)) of earnings in the Quarter
Horse in order to evaluate the inclusion of this trait in breeding programs.
Records from 14,754 races of 2443 horses from 1978-2009 were provided by Sorocaba
Hippodrome, Sao Paulo, Brazil. All ancestors of the registered horses were
included in the pedigree file until the 4th generation. Log-transformed
performance measures (LPM) were analyzed for animals aged 2, 3, and 4 years and
during their entire career. The h(2) estimates were obtained using a multi-trait
model and Gibbs sampling that included the effects of sex, year of race, and
animal in all analyses. Five analyses were performed: 1 in which LPM was divided
by the number of prizes, 1 in which LPM was divided by the number of race starts,
and 3 analyses that included the number of prizes, number of race starts, and
both (LPM_cNPS) as covariates. Analysis was performed with and without inclusion
of the maternal effect. Models were compared based on the deviance information
criterion and LPM_cNPS including maternal effects was found to be the best model.
The h(2) estimates and standard deviation obtained using model LPM_cNPS were 0.19
+/- 0.08, 0.21 +/- 0.08, 0.22 +/- 0.09, and 0.21 +/- 0.07 for earnings at 2, 3,
and 4 years of age and total career, respectively. Our analyses indicate that
earnings are subject to selection and can be included in breeding programs to
improve the racing performance of Quarter Horses.
PMID- 25117343
TI - Complete mitochondrial genome of a natural triploid crucian carp mutant,
Carassius auratus var. pingxiangnensis, and phylogenetic analysis of different
ploidies in crucian carp.
AB - Carassius auratus var. pingxiangnensis is a natural triploid crucian carp mutant.
In order to understand its placement and genetic background at the gene level,
the characteristics of mitochondrial DNA sequences and phylogenetic relationship
were examined. The results showed that the mitochondrial DNA is a circular double
stranded DNA molecule that is 16,576 bp in length with 13 protein-coding genes,
22 transfer RNA genes, 2 ribosomal RNA genes, and a non-coding control region.
Mitochondrial genes overlapped by a total of 40 bp in 11 different locations from
1 to 14 bp. The base composition of the C. auratus mitogenome was estimated to be
29.70% A, 26.74% C, 15.35% G, and 28.21% T. The central conserved blocks and the
conserved blocks were compared and were similar among C. auratus var.
pingxiangnensis and six other cyprinids with different ploidies. The origin of
light strand replication was similar to that of other vertebrates; it was 33 bp,
but the characteristic sequence motif 5?-GCCGG-3? at the base of the stem within
tRNA(Cys) was mutated to 5?-GGCGG- 3?. Our phylogenetic analysis based on whole
mitogenome sequences indicated that C. auratus var. pingxiangnensis was clustered
with C. auratus and then sister-grouped with Carassius gibelio. The systemic
developmental tree of crucian carp with different chromosome ploidies showed that
diploid C. auratus auratus was clustered with triploid C. auratus auratus, sister
grouped with tetraploid C. auratus auratus, and clustered with other diploid,
triploid, and tetraploid C. auratus.
PMID- 25117344
TI - Transcription factor 7-like 2 polymorphisms and diabetic retinopathy: a
systematic review.
AB - The global prevalence of type 2 diabetes mellitus (T2DM) has increased, as well
as complications including diabetic retinopathy. Polymorphisms in transcription
factor 7-like 2 (TCF7L2) have been associated with T2DM, with the strongest
association attributed to the single-nucleotide polymorphism rs7903146. In this
review, we searched the current literature to determine whether an association
exists between TCF7L2 polymorphisms rs7903146 with diabetic retinopathy. A
systematic search was performed of EMBASE, PubMed, and Scopus using the following
search terms: diabetic, retinopathy, polymorphism, genetic, transcription factor
7-like 2, TCF7L2. A manual search was also performed. There was no language or
study design restriction. Three full articles and one abstract were reviewed. All
studies were retrospective case-control studies that compared the frequency of
the wild-type CC genotype and genotypes with the risk T allele. None of the
studies found a statistically significant odds ratio. While the number of studies
examined was small, this review suggests that there is no risk of diabetic
retinopathy among individuals with the TCF7L2 polymorphisms rs7903146; however,
the polymorphism may play a small role in diabetic retinopathy. Future
prospective studies and trials involving diverse ethnicities that adjust for
confounding variables are required to understand the association between TCF7L2
polymorphisms and diabetic retinopathy.
PMID- 25117345
TI - Interleukin-1B-31 gene polymorphism in Hakka gastric cancer patients in
Guangdong, China.
AB - The aim of this study was to examine the interleukin-1B (IL-1B) gene promoter
region -31 (IL-1B-31) polymorphism distribution characteristic of Hakka gastric
cancer patients in Guangdong Province and to explore its association with gastric
cancer. We used the 1:1 case-control method, matrix-assisted laser desorption
ionization flight time mass spectrometry, and MassARRAY-IPLEX technology to
genotype IL-1B-31 (-31C> T) in 52 Hakka gastric cancer patients and 52 Hakka
control subjects in Meizhou. Three genotypes - CT, TT, and CC - of IL-1B-31 were
found in the Meizhou Hakka population. Their distribution frequencies in the
gastric cancer group were 40.38, 40.38, and 19.23%, respectively, whereas the
frequencies in control subjects were 57.69, 17.31, and 25.00%, respectively. The
differences in frequency distributions of the genotypes between the 2 groups were
statistically significant (chi-square = 6.78, P < 0.05). Subjects with the TT
genotype had a higher risk of gastric cancer compared with that in subjects
carrying the CT genotype (odds ratio = 2.857, 95% confidence interval = 1.114
7.328). This risk was more apparent in male subjects. IL-1B-31 locus polymorphism
may be associated with gastric cancer susceptibility in this population, but
additional studies with larger sample size are needed to confirm the conclusions.
PMID- 25117346
TI - Large-scale analysis of factors influencing nonalcoholic fatty liver disease and
its relationship with liver enzymes.
AB - Serum liver enzyme levels are often used effectively for the evaluation of
nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the
associations between serum liver enzyme levels and risks for NAFLD in over 8000
cases in a large-scale analysis. A cross-sectional survey with multiple stages
and random samplings was performed from May 2007 to May 2009 on 8102 workers at
Tongji University. A questionnaire was given, assessments of physical
measurements, plasma glucose, lipid profiles, and liver enzymes were made, and
real-time liver ultrasounds conducted. The prevalence of NAFLD in Tongji
University was 22.2%. It was higher in males than in females (P = 0.0023). The
body mass index, waist-to-hip ratio, serum total triglycerides, serum total
cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST),
and gamma-glutamyl transferase (GGT) values were all higher in the NAFLD group
than in the control group. For moderate and severe NAFLD patients, the ALT, AST
and GGT values were significantly increased, high density lipoprotein cholesterol
was decreased, and drinking much, heavy entertainment and less exercise were more
prevalent (P < 0.001). There were strong correlations between serum liver enzyme
levels and NAFLD (P < 0.001), with GGT being a more sensitive marker for NAFLD
than ALT or AST. ALT and GGT were independent predictors for NAFLD, and GGT was a
better predictor than ALT for NAFLD.
PMID- 25117347
TI - Different magnitude of resistance to non-depolarizing muscle relaxants in
dexamethasone-treated rat diaphragm associated with altered acetylcholine
receptor expression.
AB - The aim of this study was to investigate the influence of chronic dexamethasone
(Dex) administration on rat diaphragm sensitivity to non-depolarizing muscle
relaxants (NDMRs) and muscular nicotinic acetylcholine receptor (nAChR)
expression, which may help direct future administration of NDMRs. Adult male
Sprague-Dawley rats were randomized to receive a daily intraperitoneal injection
of Dex (600 MUg/kg body mass) or an equivalent volume of saline (N = 20 in each
group) for 14 days. We evaluated isometric twitch tensions of nerve-hemidiaphragm
preparations elicited by indirect supramaximal stimulation at 0.1 Hz. Real-time
quantitative PCR was performed to determine the mRNA expression of two nAChR
subunits (epsilon-subunit and gamma-subunit) in the diaphragm. Dex administration
markedly (P < 0.01) increased the 50% twitch depression (IC50) of the three
NDMRs. The IC50 ratio, which standardized the magnitudes of the resistance, was
the largest for atracurium, with the second largest for vecuronium and the
smallest for rocuronium (P < 0.01). The epsilon- and gamma-subunit mRNAs were
both upregulated with an increased gamma/epsilon ratio in rats exposed to Dex.
The results indicated that chronic Dex administration induces hyposensitivity to
NDMRs, the degree of which depends on the kind of neuromuscular blocker, and is
associated with increased nAChR expression.
PMID- 25117348
TI - RNA interference of leptin receptor in chicken adipocytes.
AB - In this study, chicken adipocytes were cultured to evaluate RNA interference by
the leptin receptor gene. A small interfering RNA of the leptin receptor gene was
synthesized, with a suppression rate of 60% being generated (P < 0.01). After the
knockdown of the leptin receptor, the expression levels of certain genes
decreased significantly; specifically, peroxisome proliferator-activated receptor
gamma, fatty acid synthase, adipose triglyceride lipase, and lipoprotein lipase.
In addition, a significant increase in the expression of the adiponectin gene was
documented. These results demonstrate that the leptin receptor gene might
contribute to lipid metabolism by influencing the expressions of the peroxisome
proliferator-activated receptor gamma, fatty acid synthase, adipose triglyceride
lipase, lipoprotein lipase, and adiponectin genes.
PMID- 25117349
TI - Analysis of transferability of microsatellite primers (SSR) in wild Passiflora
species and intraspecific genetic diversity in Passiflora alata.
AB - The genus Passiflora L. is the most representative of Passifloraceae, with over
500 known species, among which 150-200 originated from Brazil. In addition to the
great commercial importance of this genus for the fruit market, many of the
species have exotic flowers with a huge diversity of colors and can thereby be
exploited as ornamental plants. This study was aimed at investigating the
transferability of microsatellite primers in wild Passiflora species (P. cacao,
P. cincinnata, P. glandulosa, P. gibertii, and P. mucronata) and characterizing
29 P. alata accessions using microsatellite primers that were previously
developed in a library enriched with microsatellites from P. edulis f. flavicarpa
for P. alata. The interspecies cross-amplification rate varied, and P. cacao
exhibited the highest rate of amplification, suggesting a greater degree of
proximity to P. edulis. The study of intraspecific accessions in P. alata found
genetic similarity, with values ranging from 0.47 to 1.00 and an average
similarity of 0.74. Hence, this study revealed the intraspecific genetic
variability of P. alata in the Universidade Estadual de Santa Cruz's Active
Germplasm Bank and will lead to the adoption of mating strategies between
accessions; thus making their use more suitable for breeding purposes.
PMID- 25117350
TI - Changes in cyclic GMP level and phosphodiesterase activity during follicular
development in the rat ovary.
AB - Guanosine 3',5'-cyclic monophosphate (cGMP), as a second messenger, plays
potential roles in ovarian functions. To elucidate the role of phosphodiesterase
(PDE) in cGMP signaling during ovarian follicular development, the present study
was conducted to investigate ovarian cGMP level and cGMP-PDE activity by
radioimmunoassay (RIA) in postnatal rats, immature rats during gonadotropin
primed follicular development, ovulation and luteinization, adult rats during
normal estrous cycle, and aged rats that spontaneously developed persistent
estrus (PE). All four rat models were confirmed by histological examination of
one ovary, and the other ovary was used for RIA. In postnatal rats, cGMP level
was high at birth and decreased dramatically by Day 5, and then, it increased
maximally at Day 10 and declined at Day 21. However, cGMP-PDE activity did not
significantly change during Days 1 to 10, but increased significantly on Day 21.
In immature female rats, cGMP level markedly decreased upon treatment with equine
chorionic gonadotropin (eCG), while cGMP-PDE activity did not show any
significant changes; however, ovarian cGMP level and cGMP-PDE activity increased
after injection of an ovulatory dose of human chorionic gonadotropin (hCG) for
induction of ovulation and luteinization. In adult rats during normal estrous
cycle, cGMP level was high on proestrus and metestrus days, while cGMP-PDE
activity was high on estrus day. In PE rats, ovarian cGMP level was similar to
that in adult rats on estrus and diestrus days but lower than that on proestrus
and metestrus days; ovarian cGMP-PDE activity was lower than that on estrus days
but similar as the other estrous cycle days. In addition, there was a significant
negative correlation between ovarian cGMP level and cGMP-PDE activity during
normal estrous cycles in the adult rat (r = -0.7715, N = 16, P < 0.05), but not
in the postnatal rat (r = -0.1055, N = 20, P > 0.05). Together, the results of
our present study indicated that ovarian cGMP levels were not dependent on cGMP
PDE activity during early postnatal development, but highly dependent on cGMP-PDE
activity in the adult rat. This implies that mechanisms of cGMP signaling
involved in ovarian functions are stage-specific in the rat.
PMID- 25117351
TI - Localization and expression of histone H2A variants during mouse oogenesis and
preimplantation embryo development.
AB - Epigenetic modifications of the genome, such as histone H2A variants, ensure
appropriate gene activation or silencing during oogenesis and preimplantation
embryo development. We examined global localization and expression of the histone
H2A variants, including H2A.Bbd, H2A.Z and H2A.X, during mouse oogenesis and
preimplantation embryo development. Immunocytochemistry with specific antibodies
against various histone H2A variants showed their localization and changes during
oogenesis and preimplantation development. H2A.Bbd and H2A.Z were almost absent
from nuclei of growing oocytes (except 5-day oocyte), whereas H2A.X was deposited
in nuclei throughout oogenesis and in preimplantation embryos. In germinal
vesicle (GV) oocyte chromatin, H2A.Bbd was detected as a weak signal, whereas no
fluorescent signal was detected in GV breakdown (GVBD) or metaphase II (MII)
oocytes; H2A.Z showed intense signals in chromatin of GV, GVBD and MII oocytes.
H2A. Bbd showed very weak signals in both pronucleus and 2-cell embryo nuclei,
but intense signals were detected in nuclei from 4-cell embryo to blastula. The
H2A.Z signal was absent from pronucleus to morula chromatin, whereas a
fluorescent signal was detected in blastula nuclei. Our results suggest that
histone H2A variants are probably involved in reprogramming of genomes during
oocyte meiosis or after fertilization.
PMID- 25117352
TI - Correlation of coronary artery stenosis evaluation with left heart structure and
function by multi-slice computed tomography.
AB - The aim of this study was to determine the impact of multi-slice computed
tomography (MSCT) evaluation of coronary artery stenosis on left heart structure
and systolic function. Coronary artery CT angiography was performed in 200
patients diagnosed with coronary heart disease, and then according to the AHA
coronary artery 17-segment fractionation method, the Gensini score (GS) was
determined for every narrow segment, and one-stop assessment of the correlation
between left heart structure and function was performed. After the grouping of GS
quartiles from low to high, there were differences between different patients
with regard to LVDD, LADD, LVEDV, LVESV, MM, LVEF, and FS, while no difference in
SV and CO. GS showed linear negative correlation with LVEF and FS, and linear
positive correlation with LVDD, LADD, LVEDV, LVESV, and MM, while no correlation
with SV and CO. That is, GS of coronary artery stenosis was negatively correlated
with left ventricular systolic function and positively correlated with myocardial
mass. The narrower the coronary artery, the worse the cardiac function and the
higher the myocardial hypertrophy. Coronary artery stenosis was one of the
important causes of the decrease in left ventricular systolic function and
cardiac remodeling.
PMID- 25117353
TI - Reason and treatment of failure of proximal femoral nail antirotation internal
fixation for femoral intertrochanteric fractures of senile patients.
AB - The cause of postoperative failure after the treatment of femoral
intertrochanteric fracture with proximal femoral nail antirotation (PFNA) was
analyzed, and the reoperative methods were examined. Nine failures of 308 femoral
intertrochanteric fracture patients with PFNA were treated with femoral
prosthesis total hip replacement (THR) and reoperative internal fixation. All
nine patients were analyzed to determine the cause of failure. The causes of
failed internal fixation in the intertrochanteric-fractured patients included
perforation of the helical blade into the hip joint in three cases, cutting-out
of the helical blade exit outside in two cases, and hip varus as a result of
cutting-out the helical blade in two cases. Seven patients with failed internal
fixation were treated with THR. Two patients who had femoral shaft fractures at
the end of the nail were treated with longer PFNA. Faulty operative procedures,
unsatisfactory reductions, serious osteoporosis, and incorrect positioning of the
helical blade were the most important factors responsible for the failed internal
fixation. Satisfactory results were achieved with THR and refixation relative to
the causes of the failed internal fixation.
PMID- 25117354
TI - Effect of Jianpi Bushen prescription on the expression of SHP-1 and apoptosis
related genes in chemically damaged model mice.
AB - We investigated the effect of Jianpi Bushen prescription (JBP) on the expression
of the SHP-1 and apoptosis-related genes in chemically damaged model mice and a
compound e-jiao slurry (EJS) group (positive control). Kunming mice received an
abdominal injection of 100 mg/kg cyclophosphamide once a day for 3 consecutive
days to induce chemical damage. The mice underwent lavage at a suspension of 0.1
g/kg low-dose JBP (100%), high-dose JBP (200%), and 0.2 mL/10 g EJS twice a day
for 9 days. mRNA and protein expression of SHP-1 in bone marrow mononuclear cells
was detected using real-time polymerase chain reaction and Western blot; mRNA
expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax) protein was
detected by in situ hybridization. Expression of SHP-1 and Bax mRNA was
significantly upregulated in the model group compared to the control group (P <
0.05). Expression in the low-dose JBP, high-dose JBP, and EJS groups was
significantly downregulated compared with the model group (P < 0.05). The low
dose JBP group exhibited much lower SHP-1 and Bax mRNA expression levels.
Compared with controls, Bcl-2 mRNA expression was significantly reduced in the
model group (P < 0.05). Expression in the low-dose JBP, high-dose JBP, and EJS
groups significantly increased compared with the model group (P < 0.05). The low
dose JBP group showed much higher Bcl-2 mRNA expression. Therefore, JBP regulates
the expression of the SHP- 1, Bax, and Bcl-2 genes in chemically damaged mice.
PMID- 25117355
TI - Selection of sorghum hybrids grown under aluminum saturation.
AB - The purpose of this study was to evaluate 165 hybrids derived from lines
previously selected for aluminum (Al) tolerance. Nine check cultivars were used,
eight commercial hybrids and one experimental hybrid. Hybrids were evaluated at
three levels of Al saturation (0, 20 and 40% on average). The differences between
the environments were significant. Environment with 0% Al saturation yielded
29.5% more than that with 40% Al saturation, showing the importance of genotype
selection for acid soils. The best check cultivar was the hybrid DKB550. The
hybrids AG1020 and AG1040 also performed well, where the latter was more tolerant
but the former more responsive to environment improvement. The hybrid BRS304 was
susceptible to high levels of Al saturation. The three commercial BRS hybrids
(BRS310, BRS330 and BRS332) performed better than BRS304 at high Al saturation.
The hybrid BRS330 was the best BRS hybrid to grow on a field with high Al
saturation. The hybrid DKB559 performed well at high Al saturation but did not
respond to environment improvement. The hybrids 727029, 727039, 729041, 729095,
729109, AG1040, and DKB550 were tolerant to higher levels of Al saturation and
responsive to environment improvement, and showed good stability and adaptability
at both low and high Al saturation.
PMID- 25117356
TI - Genetic diversity and population structure in Harpadon nehereus based on sequence
related amplified polymorphism markers.
AB - In this study, the genetic diversity among ten populations of the Bombay duck was
studied on the basis of sequence-related amplified polymorphism (SRAP). The ten
populations were collected from the East China Sea and South China Sea areas. A
total of 98 loci were obtained from 292 individuals using eight SRAP primers. The
average proportion of polymorphic loci, genetic diversity (H), and Shannon's
information index were 75.20%, 0.2478, and 0.3735, respectively. Nei's genetic
distance and Shannon's information index between the ten populations ranged from
0.0410 to 0.3841 and from 0.2396 to 0.4506, and the averages Nei's gene diversity
index (H = 0.2478) and Shannon's information index (I = 0.3735) at the population
level were high. AMOVA showed that most of the variation was within populations
(71.74%), and only 28.26% of the variation was between populations. The neighbor
joining tree based on genetic distance revealed that significant genealogical
structure existed throughout the examined range of the Bombay duck. The results
demonstrated that SRAP marker was an effective tool for the assessment of genetic
diversity in the Bombay duck. The results could be used for further protection of
the germplasm resource of the Bombay duck.
PMID- 25117358
TI - Polyploidy and epigenetic events in the evolution of Anura.
AB - This article reviews the polyploidy events that have long been demonstrated to
play a role in the evolution of Anura, while also discussing the importance of
epigenetic control of gene expression and diversity. Findings on Brazilian
autopolyploid anurans, mainly of the genus Odontophrynus, obtained in previous
studies on their cytogenetics, chromatin ultrastructure, and molecular gene
regulation are discussed here. Our data on genome duplication and on epigenetic
events were analyzed here regarding phylogenetic trees, including the classic 2R
model for vertebrate evolution and the growing evidence of similar epigenetic
mechanisms in animal and allopolyploid plants. We propose that polyploidy and
epigenetic events led to rapid Anura diversity and speciation. Also, recent
advances in molecular studies in other organisms led us to revisit some
controversial models of evolution.
PMID- 25117357
TI - Molecular characterization and functional analysis of a Flowering locus T homolog
gene from a Phalaenopsis orchid.
AB - Warm day and cool night conditions significantly induce reproductive spike
formation in Phalaenopsis plants; hence, determining the flowering mechanism
regulating the reproductive transition is important. Flowering locus T (FT) plays
important roles in flowering induction in several plants. To explore spike
induction by warm days and cool nights in Phalaenopsis orchids, we isolated the
FT (PhFT) from Phalaenopsis hybrid Fortune Saltzman. The cDNA of PhFT was 809-bp
long and contained a 531-bp open reading frame encoding a putative protein of 176
amino acids, a 58-bp 5'-untranslated region (UTR), and a 220-bp 3'-UTR. The
predicted molecular mass of PhFT was 19.80 kDa, with an isoelectric point of
8.68. The PhFT was predicted to possess the conserved functional regions of the
phosphatidylethanolamine-binding protein superfamily. Nucleotide sequence data
indicated that PhFT contained 3 introns and 4 exons. Sequence alignment and
phylogenetic analyses of PhFT revealed high homology to the FT proteins of
Cymbidium goeringii and Oncidium Gower Ramsey. Quantitative real-time polymerase
chain reaction analysis indicated that PhFT mRNA was expressed in roots, apical
leaves, mature leaves, and flowers. In flowers, PhFT was expressed more in
developing floral buds than in mature flowers and was predominantly expressed in
ovaries and petals. Ectopic expression of PhFT in Arabidopsis ft-1 mutants showed
novel early-flowering phenotypes that lost their siliques. Our results indicated
that the ectopic expression of PhFT could partially complement the late flowering
defect in transgenic Arabidopsis ft-1 mutants. Our findings suggest that PhFT is
a putative FT homolog in Phalaenopsis plants that regulates flowering transition.
PMID- 25117359
TI - Molecular study of Astyanax altiparanae (Osteichthyes, Characidae) as a probable
species complex.
AB - Astyanax altiparanae, belonging to the bimaculatus group, which includes species
with similar colors and morphology, occurs in the upper Parana River basin. As
the use of mitochondrial DNA has made great strides in the diagnosis of species,
in previous researches, two strains were detected in A. altiparanae with a high
divergence in the D-loop region, provisionally called AltoPR and AltoPR-D.
Evidence led to the hypothesis that the two strains did not belong to the same
species. Phylogenetic hypotheses were produced by maximum-likelihood. Mean
internal distances of the AltoPR and AltoPR-D groups were respectively 0.002 and
0.003, with the distance between them being 0.037. Sequences from GenBank of
specimens collected from the Paraiba do Sul River basin were also divided into
two groups, of which one may be identified as AltoPR. Since the other group
provided an intermediate distance when compared to AltoPR-D, an in-depth
investigation was required. The other species analyzed showed a greater distance
and was revealed to be a monophyletic taxon. The results suggested that they are
really two species and that neither corresponds to the other species used in the
current study.
PMID- 25117360
TI - Value of C-arm computed tomography in radiofrequency ablation of small lung
lesions.
AB - This study aimed to explore the value of C-arm computed tomography (CT)
applications in radiofrequency ablation (RFA) of small lung lesions. The puncture
success rate, cumulative survival rate, tumor response rate, complications, and
radiation dose during C-arm CT-guided RFA of 36 small lung lesions in 34 patients
were analyzed. In 35 RFA procedures for 36 small lung lesions, the puncture
success rate was 100%. There were 7 cases of complications, including 4 cases of
pneumothorax (puncture suction or closed chest drainage was not required) and 3
cases of hemoptysis. The cumulative survival rate in the 34 patients after RFA
was 100% at 6 months, 69.0% at 1 year, and 60.0% at 2 years. In assessments of 36
foci imaged during the follow-up period, the total response rates at 1 month, 3
months, and 6 months were 77.8% (28/36), 69.7% (23/33), and 61.3% (19/31),
respectively. The mean cumulative dose and average effective dose during surgery
were 120.1 +/- 61.4 mGy and 3.5 +/- 1.7 mSv, respectively. The application of C
arm CT to RFA of small lung lesions could provide abundant information to the
surgeon and increase the lesion puncture success rate and is considered to be a
promising image-guided technology.
PMID- 25117361
TI - Identification of floral genes for sex determination in Calamus palustris Griff.
by using suppression subtractive hybridization.
AB - Calamus palustris Griff. is an economically important dioecious rattan species in
Southeast Asia. However, dioecy and onset of flowering at 3-4 years old render
uncertainties in desired female:male seedling ratios to establish a productive
seed orchard for this rattan species. We constructed a subtractive library for
male floral tissue to understand the genetic mechanism for gender determination
in C. palustris. The subtractive library produced 1536 clones with 1419 clones of
high quality. Reverse Northern screening showed 313 clones with differential
expression, and sequence analyses clustered them into 205 unigenes, including 32
contigs and 173 singletons. The subtractive library was further validated with
reverse transcription-quantitative polymerase chain reaction analysis. Homology
identification classified the unigenes into 12 putative functional proteins with
83% unigenes showing significant match to proteins in databases. Functional
annotations of these unigenes revealed genes involved in male flower development,
including MADS-box genes, pollen-related genes, phytohormones for flower
development, and male flower organ development. Our results showed that the male
floral genes may play a vital role in sex determination in C. palustris. The
identified genes can be exploited to understand the molecular basis of sex
determination in C. palustris.
PMID- 25117362
TI - Characteristics of growth traits and their effects on body weight of G1
individuals in the mud crab (Scylla paramamosain).
AB - The mud crab (Scylla paramamosain) is considered a potentially important marine
crab species for selective breeding. Here, we first examined sex ratio and
differences in 16 growth traits between females and males in a G1 population of
S. paramamosain, and we then analyzed the correlation between these growth traits
and their effects on body weight (BW). Of these growth traits, nine were
significantly different between sexes. In females, the correlation coefficients
in all trait pairs ranged from 0.524 to 0.997. The traits carapace length (CL)
and distance between lateral spine 2 (DLS2) significantly affected BW directly,
with the path coefficients being 1.124 and -0.186, respectively. The
determination coefficients of traits CL and DLS2 to BW were 1.263 and 0.035 with
the total value being 0.951, indicating that the two traits were the key factors
affecting BW. In males, the correlation coefficients in all trait pairs ranged
from 0.881 to 0.999. The three traits body height (BH), fixed finger height of
the claw (FFHC), and meropodite length of pereopod 2 (MLP2) significantly
affected BW directly, with the path coefficients being 0.484, 0.300, and 0.225,
respectively. The determination coefficients of traits BH, FFHC and MLP2 to BW
were 0.234, 0.090 and 0.051, with the total value being 0.967, indicating that
these three traits played a key role in affecting BW. Moreover, we constructed
two best-fit linear regression equations, which were Y (BW) = 4.969 X1 (CL) -
0.758 X2 (DLS2) - 140.177 and Y (BW) = 3.806 X1 (BH) + 2.371 X2 (FFHC) + 1.725 X3
(MLP2) - 123.559 in females and males, respectively.
PMID- 25117363
TI - Effects of simulated weightlessness on cellular morphology and biological
characteristics of cell lines SGC-7901 and HFE-145.
AB - We investigated the effects of simulated weightlessness on cellular morphology,
proliferation, cell cycle, and apoptosis of the human gastric carcinoma cell line
SGC-7901 and the human gastric normal cell line HFE-145. A rotating clinostat was
used to simulate weightlessness. The Image-Pro4.5 image analysis system was used
for morphometric analysis. Proliferating cell nuclear antigen expression was
examined by immunohistochemical staining. Changes in the cell cycle were examined
using a cytometer. Apoptosis was measured using the terminal dUTP nick-end
labeling (TUNEL) method. When subjected to simulated weightlessness, the cellular
morphology of SGC-7901 cells was changed at 12, 24, 48, and 72 h, cell conversion
from the G1 to S phase was blocked, proliferation was inhibited at 48 and 72 h,
and the apoptosis index was increased at 72 h. The same changes were observed for
HFE-145 cells at 12 h when subjected to simulated weightlessness, but no
significant changes were found afterward compared with controls. SGC-7901 cells
change their cellular morphology and biological characteristics during clinostat
simulated weightlessness at 72 h, but HFE-145 cells only change at 12 h and adapt
to simulated weightlessness after that point.
PMID- 25117364
TI - Comparative study of DNA extraction methodologies from goat sperm and its effects
on polymerase chain reaction analysis.
AB - Successful DNA extraction is indispensable for molecular methods based on
polymerase chain reaction (PCR); however, goat sperm DNA extraction is limited.
Thus, the aim of this study was to evaluate three methods to extract DNA from
goat sperm for use in PCR. Eight goat semen pools were used for DNA extraction by
using the DNeasy Blood & Tissue Kit, phenol-chloroform, and Chelex-100 methods.
DNA samples were analyzed spectrophotometrically to determine the DNA
concentration and purity, visualized on 0.8% agarose gel, and used at different
amounts (150, 100, 50, 10, and 1 ng) for PCR with electrophoresis, followed by
1.5% agarose gel electrophoresis. The quantity of DNA extracted with Chelex-100
was higher (P < 0.05) than that obtained with either the DNeasy Blood & Tissue
Kit or the phenol-chloroform method, with the phenol-chloroform method yielding a
greater quantity (P < 0.05) than the kit. The DNeasy Blood & Tissue Kit produced
a higher (P < 0.05) purity product than the Chelex-100 method, and all samples
obtained by the three protocols were positive for DNA, as assessed by
electrophoresis. All of the different concentrations of DNA produced by these
methods were amplified by PCR, although for DNA produced by the phenol-chloroform
method, PCR was only possible after complementary purification. In conclusion,
the Chelex-100 method is cheap, secure, simple, fast, and effective, and is a
potential tool for extracting goat sperm DNA without limitations in PCR.
PMID- 25117365
TI - Screening and characterization of new microsatellite markers in Fenneropenaeus
penicillatus.
AB - Fenneropenaeus penicillatus, with high protein and low fat, is a commercially
important aquatic product in China. Microsatellite loci were developed according
to the protocol of fast isolation by amplified fragment length polymorphism of
sequences containing repeats. Eight new polymorphic microsatellite markers for F.
penicillatus were identified, and 32 wild individuals were used to evaluate the
degree of polymorphism of these markers. The polymorphism information content
ranged from 0.2703 to 0.7598, and the number of alleles per locus varied from 3
to 6. The observed and expected heterozygosities were 0.1613-0.5556 and 0.2347
0.7387, respectively. No significant deviations from Hardy-Weinberg equilibrium
(P > 0.00625) were detected. These polymorphic microsatellite loci will be useful
to study the genetic diversity and population structure of F. penicillatus.
PMID- 25117366
TI - Influence of neural stem cell transplantation on angiogenesis in rats with spinal
cord injury.
AB - We examined the influence of neural stem cell transplantation on angiogenesis in
rats with spinal cord injury. Sixty rats with spinal cord injury were divided
into an experimental group and a control group and given neural stem cells or an
equivalent amount of phosphate-buffered saline by intravenous transplantation,
respectively. Basso, Beattie, and Bresnahan (BBB) motor function assessment was
performed in rats at different times after transplantation, and von Willebrand
factor (vWF) immunofluorescence and Western blot analysis of vascular endothelial
growth factor (VEGF) protein were also performed. The BBB scores of rats in the 2
groups were both zero before transplantation. The BBB score gradually increased
over time. The BBB score of the experimental group showed no significant
difference compared with that of the control group (P > 0.05) 7 days after
transplantation. The BBB score of the experimental group was significantly
improved compared with that of the control group 14 days after transplantation (P
< 0.05). vWF-positive cells and VEGF protein expression in the experimental group
were significantly increased compared with those in the control group 7 and 14
days after transplantation, respectively (P < 0.05). Neural stem cell
transplantation may promote angiogenesis by inducing VEGF expression as well as
improve functional recovery of limb movements.
PMID- 25117367
TI - Source of bacterial RNA in chronic otitis media with effusion.
AB - The purpose of this study was to investigate whether the bacterial RNA detected
by polymerase chain reaction (PCR) and reverse transcription (RT)-PCR methods in
middle ear effusion (MEE) for pediatric chronic otitis media with effusion (OME)
originated from live bacteria. Degradation of RNA was observed by spectroscopic
analysis; we also investigated the effect of MEE on the digestive activity of
RNase. The optical density of RNA solution was stable within 3 h. MEE could not
degrade the RNA, while RNase could rapidly digest the RNA. MEE significantly
inhibited the digestive activity of RNase, and the inhibitory effect was
correlated with MEE concentration. The bacterial DNA and RNA detected by PCR and
RT-PCR methods may not originate from live bacteria, but might instead originate
from residues from previous bacterial infection(s). Chronic OME is not an
infection of live bacteria, and therefore, antibiotics should be used with
caution for clinical treatment of pediatric chronic OME.
PMID- 25117368
TI - Development of novel simple sequence repeat markers from a genomic sequence
survey database and their application for diversity assessment in Jatropha curcas
germplasm from Guatemala.
AB - The last few years have seen a significant increase in the number of large-scale
sequencing projects generating whole genome databases. These sequence databases
can be surveyed (genome sequence survey) for tandem repeats as an alternative
means to develop microsatellites for monitoring and selecting natural populations
and cultivars of Jatropha curcas. A total of 100 tandem repeats were revealed
from mining 368 genomic surveyed sequences available in the Kazusa DNA Research
Institute database. Twenty microsatellite sequences were successfully amplified,
resulting in repeatable and scorable polymerase chain reaction products.
Genotyping of J. curcas accessions from the Guatemalan population revealed 18
polymorphic loci. The average number of alleles per locus was 6.9, and allelic
sizes ranged from 94 to 299 bp. Expected and observed heterozygosities ranged
from 0.118 to 0.906 and from 0.082 to 0.794, respectively. Polymorphic
information content values ranged from 0.114 (JcSSR-34) to 0.886 (JcSSR-33) with
an average of 0.627. Analysis with Micro-Checker indicated few null alleles for
locus JcSSR-37 in Guatemalan populations, which may be a possible cause of its
deviation from Hardy-Weinberg equilibrium, even after Bonferroni's correction. No
loci showed significant linkage disequilibrium. These microsatellite loci are
expected to be valuable molecular markers in J. curcas because they show high
levels of polymorphism and heterozygosity.
PMID- 25117369
TI - Formation of and countermeasures for subacute coronary stent thrombosis in
elderly diabetic patients.
AB - The aim of this study was to evaluate and investigate the pathogenetic mechanism
and countermeasures of subacute thrombosis (SAT) after coronary stenting in
elderly diabetic patients. The clinical characteristics and pathogenetic
mechanisms in 3 cases of SAT after stent implantations in elderly diabetic
patients were retrospectively examined to determine the treatment strategies for
SAT. Among 98 patients with diabetes who had coronary stents implanted or were
>60 years of age, three (3.06%) had SAT. One case of SAT was diagnosed by
angiography; coronary balloon dilatation, thrombolysis, and re-perfusion resulted
in full recovery in this case. The second case involved potential SAT, and in the
third case, SAT was not ruled out. Two cases were characteristic of ST-segment
elevation myocardial infarction, and one case, in which SAT was not ruled out,
resulted in sudden death. SAT within a stent may be related to intraoperative
stent malapposition caused by a grade C lesion, age, diabetes, chronic total
occlusion, or postoperative irregular administration of medication.
PMID- 25117372
TI - Repeated whole-lung lavage for unremitting pulmonary alveolar proteinosis: a
eight-year follow-up of a case.
AB - Pulmonary alveolar proteinosis (PAP) is a rare clinical syndrome that was first
described in 1958. To date, whole-lung lavage (WLL) is still the gold-standard
therapy for PAP. Herein, we report the case of a male patient who was diagnosed
with PAP by open-lung biopsy 8 years prior to presentation at our clinic. The man
underwent his first WLL in 2004 and showed marked clinical and radiological
improvement after the operation. However, after his original presentation,
proteinaceous material continued to accumulate in his lungs. Lavage was performed
four additional times, but these attempts failed to arrest the decline in
pulmonary function. Each lavage resulted in significant, although transient,
clinical improvement.
PMID- 25117371
TI - Variants -250G/A and -514C/T in the LIPC gene are associated with hypertensive
disorders of pregnancy in Chinese women.
AB - We examined the influence of the promoter polymorphisms -250G/A (rs2070895) and
514C/T (rs1800588) in the human hepatic lipase (LIPC) gene on dyslipidemia and
hypertensive disorders complicating pregnancy (HDCP) in a Chinese population.
Clinically defined HDCP patients (N = 321) and healthy pregnant women (N = 331)
were recruited and genotyped using polymerase chain reaction-restriction fragment
length polymorphism for the two LIPC single nucleotide polymorphisms (SNPs). The
results showed significant relationships between HDCP and triglycerides,
apolipoprotein A1, and high-density lipoprotein cholesterol (P < 0.05), which
confirmed that HDCP was accompanied by dyslipidemia. The results also
demonstrated that in gestational hypertension (GH) patients, both total
cholesterol (TC) and systolic blood pressure (SBP) levels were related to the two
SNPs (P <= 0.004), although no significant association was found between HDCP and
LIPC genotypes or alleles. Significant linkage disequilibrium of the two SNPs was
found in both HDCP patients (R(2) = 0.867) and controls (R(2) = 0.91). Body mass
index (BMI) was associated with -250G/A in women with mild preeclampsia (MPE) (P
= 0.01). Carriers of the mutant homozygote -250AA genotype presented higher BMI
in the MPE group. In conclusion, the LIPC -250G/A and -514C/T variants influenced
TC and SBP levels in GH patients and the BMI level in the MPE group, although
there was no evidence to validate an association between HDCP and LIPC allele,
genotype, or haplotype frequencies.
PMID- 25117370
TI - Evaluation of attenuated Salmonella choleraesuis-mediated inhibin recombinant DNA
vaccine in rats.
AB - DNA vaccination has been studied intensively as a potential vaccine technology.
We evaluated the effect of an attenuated Salmonella choleraesuis-mediated inhibin
DNA vaccine in rats. First, 15 rats were treated with different doses of an
inhibin vaccine to evaluate vaccine safety. Next, 30 rats were divided into 3
groups and injected intramuscularly with the inhibin vaccine two (T1) or three
times (T2) or with control bacteria (Con) at 4-week intervals. The inhibin
antibody levels increased [positive/negative well (P/N) value: T1 vs Con = 2.39
+/- 0.01 vs 1.08 +/- 0.1; T2 vs Con = 2.36 +/- 0.1 vs 1.08 +/- 0.1, P < 0.05] at
week 2 and were maintained at a high level in T1 and T2 until week 8, although a
small decrease in T2 was observed at week 10. Rats in the T1 group showed more
corpora lutea compared with the Con group (10.50 +/- 0.87 vs 7.4 +/- 0.51, P <
0.05). Estradiol (0.439 +/- 0.052 vs 0.719 +/- 0.063 ng/mL, P < 0.05) and
progesterone (1.315 +/- 0.2 vs 0.737 +/- 0.11 ng/mL, P < 0.05) levels differed
significantly at metestrus after week 10 between rats in the T1 and Con groups.
However, there were no significant differences in body, ovary, uterus weights, or
pathological signs in the ovaries after immunization, indicating that this
vaccine is safe. In conclusion, the attenuated S. choleraesuis-mediated inhibin
vaccine may be an alternative to naked inhibin plasmids for stimulating ovarian
follicular development to increase the ovulation rate in rats.
PMID- 25117373
TI - A case-control study indicates that the TRIB1 gene is associated with pancreatic
cancer.
AB - Pancreatic cancer is a malignant neoplasm originating from transformed cells
arising in tissues that form the pancreas. To investigate whether the tribbles
homolog 1 (Drosophila) gene (TRIB1) is associated with pancreatic cancer in the
Chinese Han population, we conducted this case-control study and genotyped 3
single nucleotide polymorphisms (rs2980879, rs2980874, and rs2235108) of the
TRIB1 gene in 182 patients and 359 normal controls of Chinese Han origin and
analyzed their association. The results showed that the rs2980879 polymorphism
was associated with pancreatic cancer [allele: P = 0.023434, genotype: P =
0.03005; odds ratio (OR) and 95% confidence interval (CI) = 0.727788 (0.552664
0.958404)], whereas the rs2980874 polymorphism had no association with pancreatic
cancer [allele: P = 0.749885, genotype: P = 0.699533; OR and 95%CI = 1.041981
(0.809196-1.341734)], and the rs2235108 polymorphism was not associated with the
disease [allele: P = 0.629475, genotype: P = 0.547534, OR and 95%CI = 1.128290
(0.690829-1.842770)]. Haplotype analyses and linkage disequilibrium tests were
also conducted, and the results showed that these 3 loci are not in the same
block. In conclusion, our study indicated that the TRIB1 gene is associated with
pancreatic cancer. More studies with larger samples are needed in order to
support this finding.
PMID- 25117374
TI - Selection of DNA barcoding loci and phylogenetic study of a medicinal and endemic
plant, Plectranthus asirensis J.R.I. Wood from Saudi Arabia.
AB - Genuine medicinal plant materials are very important for potential crude drug
production, which can be used to cure many human diseases. DNA barcoding of
medicinal plants is an effective way to identify adulterated or contaminated
market materials, but it can be quite challenging to generate barcodes and
analyze the data to determine discrimination power. The molecular phylogeny of a
plant species infers its relationship to other species. We screened the various
loci of the nuclear and chloroplast genome for the barcoding of Plectranthus
asirensis, an endemic plant of Saudi Arabia. The chloroplast genome loci such as
rps16 and rpoB showed maximum similarity to taxa of the same and other genera via
BLAST of the National Center for Biotechnology Information (NCBI) GenBank
database; hence, they are less preferable for the development of a DNA barcode.
However, nrDNA-ITS and chloroplast loci rbcL and rpoC1 showed less similarity via
BLAST of the NCBI GenBank database; therefore, they could be used for DNA
barcoding for this species.
PMID- 25117375
TI - Beneficial metabolic phenotypes caused by loss-of-function APOC3 mutations.
PMID- 25117376
TI - Stiffness of cross-linked poly(dimethylsiloxane) affects bacterial adhesion and
antibiotic susceptibility of attached cells.
AB - In this study, Escherichia coli RP437 and Pseudomonas aeruginosa PAO1 were used
as model strains to investigate the early stage biofilm formation on
poly(dimethylsiloxane) (PDMS) surfaces with varying stiffness, which were
prepared by controlling the degree of cross-linking (base:curing agent ratios of
5:1, 10:1, 20:1, and 40:1 were tested). An inverse correlation between cell
adhesion and substrate stiffness was observed for both species. Interestingly, it
was found that the cells attached on relatively stiff substrates (5:1 PDMS) were
significantly smaller than those on relatively soft substrates (40:1 PDMS). In
addition to the difference in size, the cells on 5:1 PDMS substrates were also
found to be less susceptible to antibiotics, such as ofloxacin, ampicillin, and
tobramycin, than the cells attached on 40:1 PDMS substrates. These results reveal
that surface stiffness is an important material property that influences the
attachment, growth, and stress tolerance of biofilm cells.
PMID- 25117377
TI - Microfluidic genotyping by rapid serial PCR and high-speed melting analysis.
AB - BACKGROUND: Clinical molecular testing typically batches samples to minimize
costs or uses multiplex lab-on-a-chip disposables to analyze a few targets. In
genetics, multiple variants need to be analyzed, and different work flows that
rapidly analyze multiple loci in a few targets are attractive. METHODS: We used a
microfluidic platform tailored to rapid serial PCR and high-speed melting (HSM)
to genotype 4 single nucleotide variants. A contiguous stream of master mix with
sample DNA was pulsed with each primer pair for serial PCR and melting. Two study
sites each analyzed 100 samples for F2 (c.*97G>A), F5 (c.1601G>A), and MTHFR
(c.665C>T and c.1286A>C) after blinding for genotype and genotype proportions.
Internal temperature controls improved melting curve precision. The platform's
liquid-handling system automated PCR and HSM. RESULTS: PCR and HSM were completed
in a total of 12.5 min. Melting was performed at 0.5 degrees C/s. As expected,
homozygous variants were separated by melting temperature, and heterozygotes were
identified by curve shape. All samples were correctly genotyped by the
instrument. Follow-up testing was required on 1.38% of the assays for a
definitive genotype. CONCLUSIONS: We demonstrate genotyping accuracy on a novel
microfluidic platform with rapid serial PCR and HSM. The platform targets short
turnaround times for multiple genetic variants in up to 8 samples. It is also
designed to allow automatic and immediate reflexive or repeat testing depending
on results from the streaming DNA. Rapid serial PCR provides a flexible genetic
work flow and is nicely matched to HSM analysis.
PMID- 25117378
TI - Effects of a very congested match schedule on body-load impacts, accelerations,
and running measures in youth soccer players.
AB - PURPOSE: To analyze the effects of a very congested match schedule on the total
distance (TD) covered, high-intensity-running (HIR) distance, and frequency of
accelerations and body-load impacts (BLIs) performed in a team of under-15 soccer
players (N=10; 15.1+/-0.2 y, 171.8+/-4.7 cm, 61+/-6.0 kg) during an international
youth competition. METHODS: Using global positioning systems, player performances
were repeatedly monitored in 5 matches performed over 3 successive days. RESULTS:
Significant differences were observed between matches (P<.05) for the frequency
of accelerations per minute, BLIs, and BLIs per minute. No differences were
observed for the TD covered, TD run per minute, number of high-intensity runs,
distance covered in HIR, per-minute peak running speed attained, or frequency of
accelerations. The frequency of accelerations per minute decreased across the
competition while BLIs were higher during the final than in all other matches.
CONCLUSIONS: These results suggest that BLIs and acceleration might be used as an
alternative means to represent the external load during congested match schedules
rather than measures related to running speed or distance covered.
PMID- 25117380
TI - QT Interval Prolongation Associated with Azithromycin/Methadone Combination.
AB - This report documents the occurrence of QT prolongation in a 57-year old man, on
methadone replacement therapy, treated with azithromycin for community acquired
pneumonia. This case highlights a hitherto unknown drug interaction. In light of
ever-increasing use of azithromycin, it is imperative that azithromycin be used
with caution in patients who are already on drugs that are known to cause QT
prolongation or that cause torsades de pointes.
PMID- 25117379
TI - Electrospun polyurethane/hydroxyapatite bioactive scaffolds for bone tissue
engineering: the role of solvent and hydroxyapatite particles.
AB - Polyurethane (PU) is a promising polymer to support bone-matrix producing cells
due to its durability and mechanical resistance. In this study two types of
medical grade poly-ether urethanes Z3A1 and Z9A1 and PU-Hydroxyapatite (PU-HA)
composites were investigated for their ability to act as a scaffold for tissue
engineered bone. PU dissolved in varying concentrations of dimethylformamide
(DMF) and tetrahydrofuran (THF) solvents were electrospun to attain scaffolds
with randomly orientated non-woven fibres. Bioactive polymeric composite
scaffolds were created using 15 wt% Z3A1 in a 70/30 DMF/THF PU solution and
incorporating micro- or nano-sized HA particles in a ratio of 3:1 respectively,
whilst a 25 wt% Z9A1 PU solution was doped in ratio of 5:1. Chemical properties
of the resulting composites were evaluated by FTIR and physical properties by
SEM. Tensile mechanical testing was carried out on all electrospun scaffolds. MLO
A5 osteoblastic mouse cells and human embryonic mesenchymal progenitor cells, hES
MPs were seeded on the scaffolds to test their biocompatibility and ability to
support mineralised matrix production over a 28 day culture period. Cell
viability was assayed by MTT and calcium and collagen deposition by Sirius red
and alizarin red respectively. SEM images of both electrospun PU scaffolds and PU
HA composite scaffolds showed differences in fibre morphology with changes in
solvent combinations and size of HA particles. Inclusion of THF eliminated the
presence of beads in fibres that were present in scaffolds fabricated with 100%
DMF solvent, and resulted in fibres with a more uniform morphology and thicker
diameters. Mechanical testing demonstrated that the Young's Modulus and yield
strength was lower at higher THF concentrations. Inclusion of both sizes of HA
particles in PU-HA solutions reinforced the scaffolds leading to higher
mechanical properties, whilst FTIR characterisation confirmed the presence of HA
in all composite scaffolds. Although all scaffolds supported proliferation of
both cell types and deposition of calcified matrix, PU-HA composite fibres
containing nano-HA enabled the highest cell viability and collagen deposition.
These scaffolds have the potential to support bone matrix formation for bone
tissue engineering.
PMID- 25117381
TI - The economic and medical costs of alcohol consumption in Japan.
PMID- 25117382
TI - Chemokine Receptor 7 Implications of Spleen Dendritic Cells in Multiple-organ
Dysfunction Syndrome in Mice.
AB - OBJECTIVE: This study aims to explore the chemokine receptor 7 (CCR7) expression
of spleen dendritic cells (DCs) and their role in the changes of migration and
activity of spleen DCs in multiple-organ dysfunction syndrome (MODS). METHODS:
The MODS model of mice was reproduced. The mice were randomly assigned to the
following groups: normal, three-hour to six-hour, 24-hour to 48-hour, and 10-day
to 12-day post-zymosan injection. CD11c and CD205 were analysed by
immunohistochemistry; the expressions of CD86 and CCR7 of DCs were studied using
flow cytometry analyses. RESULTS: In normal mice, many DCs were found at the
margin between the red and white pulp. In the three-hour to six-hour and 24-hour
to 48-hour group, DC effectively upregulated CD86 and CCR7, and they were
distributed in T- cell areas. In the 10-day to 12-day group, DCs were distributed
at the margin by the immature form. CONCLUSION: The CCR7 expression level of DCs
had close correlations with the migration of DCs. Chemokine receptor 7 can be
used to evaluate the migration and functional activity of DCs in MODS.
PMID- 25117383
TI - The Changes of Muscle FGF-6 Expression at Different Time Points after Exercise
induced Muscle Damage.
AB - OBJECTIVE: To investigate the changes of fibroblast growth factor (FGF)-6
expression in the regeneration and repair process after exercise-induced muscle
damage (EIMD) and the relationship with skeletal muscle regeneration and repair.
METHODS: The expression of FGF-6 at different time points was examined by reverse
transcription-polymerase chain reaction (PCR) and immunohistochemistry staining
after a downhill treadmill exercise. Skeletal muscle injury and regeneration at
different times after EIMD was assessed by haematoxylin and eosin (H and E)
staining. RESULTS: The FGF-6 protein expression was initially elevated and
followed by a gradual reduction, while the changes of FGF-6 mRNA were almost all
raised after the treadmill exercise. CONCLUSION: The results point out that FGF-6
is closely related to skeletal muscle regeneration and repair, probably implying
a dual function in muscle regeneration.
PMID- 25117384
TI - Study on vascular endothelial growth factor and its receptor in the vitreous of
diabetic rats.
AB - OBJECTIVE: To investigate the vitreous level of vascular endothelial growth
factor (VEGF) and kinase insert domain-containing receptor (KDR) in diabetic
rats, and to explore the role of VEGF and KDR in diabetic retinopathy. METHODS:
Eighty-four adult Wistar rats were randomly divided into two groups. Fifty-eight
rats in group A were injected intraperitoneally with streptozotocin to induce
diabetes and 20 rats in group B were injected with physiological saline. Blood
glucose meter was used to detect the blood glucose level at 72 hours after
injection; blood glucose level >= 16.67 mmol/L was considered to be successful
modelling. Blood glucose level was assayed and body mass was measured on the same
modelling day, one week, two weeks and four weeks after modelling. Four weeks
after modelling, the vitreous was taken, and the VEGF and KDR levels were
detected by enzyme-linked immunosorbent assay (ELISA). The eyeballs were fixed
with paraform and embedded by petrolin for haematoxylin and eosin (H and E)
staining. RESULTS: Forty-two rats survived and 16 rats died in group A. No rats
died in group B. The blood glucose at one week, two weeks and four weeks between
the two groups had statistical differences (p < 0.05). The weight at one week and
two weeks between the two groups was not different but there was statistical
difference at four weeks between the two groups (p < 0.01). The ELISA results
showed that the VEGF and KDR levels were 0.276 +/- 0.026 ng/mL and 2.936 +/-
0.295 ng/mL in group A, 0.231 +/- 0.021 ng/mL and 2.394 +/- 0.227 ng/mL in group
B, respectively. The VEGF and KDR levels of group A were higher than those of
group B (p < 0.05). CONCLUSIONS: The changes of VEGF and KDR levels in the
vitreous of diabetic rats were related to the early retinopathy induced by
diabetes.
PMID- 25117385
TI - Role of interleukin-6, gamma interferon and adenosine deaminase markers in
management of pleural effusion patients.
AB - OBJECTIVE: Pleural effusion is a common diagnostic and clinical problem.
Neoplasms and tuberculosis are the most frequent diagnostic causes of such
effusions. Conventional laboratory methods for diagnosis of such effusion are
inefficient because tubercle bacilli are rarely seen in direct examinations of
pleural fluid. The present study evaluates interleukin-6 (IL-6), gamma interferon
(IFN-gamma) and adenosine deaminase (ADA) as diagnostic tools in pleural
effusion. MEHTODS: Interleukin-6, IFN-gamma and ADA were measured in pleural
fluid from the patients, with exudative pleural effusion from tuberculous,
malignant and postpneumonic origin and transudative pleural effusion of systemic
origin in order to evaluate the diagnostic utility of these. RESULTS: The three
markers were detectable in all effusions with significantly high levels in
exudative as compared to transudative effusions. There was a statically
significant difference noticed in tuberculous as compared to malignant and
postpneumonic origin and transudative pleural effusion. CONCLUSION: We concluded
that IL-6, IFN-gamma and ADA levels in pleural effusion are sensitive parameters
to differentiate an exudate from a transudate and they can also differentiate
exudates of different aetiology. Finally, the results suggest that there is a
remarkable difference in production of these three markers in exudative pleural
effusions as compared to transudative pleural effusions.
PMID- 25117386
TI - Diagnostic accuracy of spot and timed measurements of urinary albumin
concentration to determine microalbuminuria in sickle cell disease.
AB - OBJECTIVE: Whereas measurement of albumin:creatinine ratio (ACR) in spot urine
samples is indicated for determining microalbuminuria, its performance or that of
urinary albumin excretion rate (UAER) in predicting microalbuminuria in sickle
cell disease (SCD) is unclear. We therefore tested the diagnostic performance of
these measures in spot and timed urine samples in predicting a UAER in 24-hour
samples. METHODS: Thirty participants with SCD had spot, two-hour and four-hour,
followed by 24-hour urine collections for ACR, urinary albumin concentration
(UAC) and UAER determinations. Receiver operating characteristic (ROC) curve
analyses were performed. RESULTS: The areas under the ROC curves for
microalbuminuria were 0.99 (CI: 0.97, 1.00) for ACR and 0.97 (CI: 0.92, 1.00) for
UAC in spot urine samples. For ACR, at the cut-point of 4.13 mg/mmol, there was
100% sensitivity and 82.6% specificity, allowing an 86.2% correct classification.
At the cut-point of UAC = 20.9 mg/L, there was 100% sensitivity and 73.9%
specificity, allowing a 79.3% correct classification. Corresponding areas for
microalbuminuria in two-hour timed samples were 0.99 (CI: 0.95, 1.00) for ACR and
0.96 (CI: 0.89, 1.00) for UAER.For ACR, the cut-point was 4.64 mg/mmol with 83.3%
sensitivity and 91.3% specificity, allowing an 89.7% correct classification.
Similarly for UAER, at the cut-point of 21.8 ug/min, there was 83.3% sensitivity
and 91.3% specificity, allowing 89.7% correct classification. CONCLUSIONS: The
diagnostic performance of ACR and UAC in a spot as well as ACR and UAER in two
hour timed urine samples in patients with SCD is excellent. Healthcare
professionals can confidently utilize these measures in this patient population.
PMID- 25117387
TI - Observer Variability in Sonographic Measurement of Kidney Sizes among Children in
Benin-City, Nigeria.
AB - AIM: To assess the level of inconsistency in replicating sonographic kidney size
measurements in a population of healthy Nigerian children. SUBJECTS AND METHODS:
In this prospective cross-sectional study, convenience sampling technique was
used to select a sample of Nigerian children. Both consent from participants and
ethical approval from the local authority were obtained before the study
commenced. Three radiologists carried out the replicate sonographic measurements
using a DP-1100 mechanical sector scanner with a 3.5 MHz convex probe. All
examinations were done with subjects in the supine oblique position. Longitudinal
and transverse scans were performed. Renal lengths and widths were measured from
the longitudinal scans while thickness was measured from the transverse scans.
Renal volumes were calculated with the ellipsoid formula. Analysis of variance,
Student's t-test, Pearson's correlation coefficient and z-test were used to test
the statistical significance of results. SPSS version 17.0 was used in the
analysis of results while statistical significance of all results was tested at p
< 0.05. RESULTS: Mean intra-observer measurement errors in replicate sonographic
measurements of kidney sizes ranged from 0.36-0.43 cm, 0.22-0.63 cm, 0.37-0.52 cm
and 5.93-9.62 ml for kidney length, width, thickness and volume, respectively.
Mean inter-observer measurement errors were in the range of 0.29-0.48 cm, 0.18
0.23 cm, 0.34-1.82 cm and 5.92-7.28 ml for length, width, thickness and volume,
respectively. Mean intra-observer errors were not statistically significant (p <
0.05) but mean inter-observer errors were (p < 0.05). Differences in all
measurement errors of right and left kidney length, width, thickness and volume
were not statistically significant (p > 0.05). Measurement errors correlated
weakly with kidney sizes. Observer errors in renal length were not significantly
different from what was reported among Caucasians (p > 0.05) whereas that of
volume was (p < 0.05). CONCLUSION: Errors in replicate sonographic kidney size
measurements obtained by a single observer were less than errors in the same
measurements by different observers; therefore, replicate sonographic
measurements by a single observer were more consistent in this population.
PMID- 25117388
TI - The Prevalence of Sexual Dysfunction among the Patients with End Stage Renal
Disease in Jamaica.
AB - BACKGROUND: Sexual performance and gratification impact quality of life. Although
recognized in the literature as a problem, sexual dysfunction among patients with
end stage renal disease (ESRD) has never been studied in Jamaica. SUBJECTS AND
METHOD: The prevalence of sexual dysfunction was determined among 268 adult
Jamaican patients (166 males, 102 females) with ESRD who had been on
haemodialysis for at least three months. Erectile dysfunction (ED) was assessed
using the International Index of Erectile Function (IIEF). Female sexual
dysfunction (FSD) was determined using the Diagnostic and Statistical Manual of
Mental Disorders, fourth edition (DSM-IV) and International Classification of
Diseases (ICD)-10 classifications of sexual disorders. Prevalence, severity of
sexual dysfunctions and relationships with the primary aetiology of ESRD and
anaemia were assessed. RESULTS: Erectile dysfunction, desire and orgasmic
disorderS were found in 91.4%, 88.3%, and 81.6% of male subjects, respectively.
The majority of male patients were dissatisfied with their performance at
intercourse after progressing to ESRD. Hypoactive sexual disorder, sexual arousal
and orgasmic disorders, and aversion sexual disorder were prevalent, found in
96%, 88.1% and 87.1% of female patients. All diabetic patients with ESRD reported
hypoactive sexual disorder and orgasmic dysfunction; arousal disorder was found
in 94.7%. Aversion sexual disorder was found more among patients with underlying
chronic glomerulonephritis. All patients with severe anaemia were found to have
hypoactive sexual disorder and among these, 87.5% and 97.8% had severe arousal
and orgasmic disorders, respectively. CONCLUSION: Sexual dysfunction among
patients with ESRD in Jamaica was prevalent in males and females. Associations
exist between sexual dysfunction and diabetes mellitus, chronic
glomerulonephritis and anaemia.
PMID- 25117389
TI - Comparison of ultrasonographic estimated fetal weight and actual birthweight
performed by residents in training at the university hospital of the west indies.
AB - OBJECTIVE: To determine the correlation of ultrasonographic estimation of fetal
weight and actual birthweight and the impact of the level of resident's training
on the results. METHODS: A prospective study of 90 women with term pregnancies.
Ultrasound estimated fetal weight (EFW) was calculated by a preprogrammed Hadlock
formula. Days from ultrasound to delivery were less than seven. The EFW was
compared to the actual birthweight at delivery. The year of training of the
resident that performed the ultrasound was recorded. Exclusion criteria included
Diabetes mellitus and known fetal anomalies. RESULTS: Mean age was 28 years,
parity zero to four, mean gestational age 38 weeks. There was an average over
estimation of 64.8 grams. The difference between mean EFW and mean BWT was not
significant (p = 0.067). The difference between mean EFW and mean BWT when
calculated according to year of residency was not significant, p = 0.075 and
0.402 for junior and senior residents, respectively. CONCLUSION: There is good
correlation between resident's ultrasonographic estimation of fetal weight and
actual birthweight at the UHWI. There was no significant difference in
correlation between senior and junior residents. Development in computer
technology might contribute to decrease in the learning curve.
PMID- 25117391
TI - Second Transurethral Resection of Bladder Tumour for the Treatment of Muscle
invasive Bladder Tumours.
AB - BACKGROUND: Exacerbations of Chronic Obstructive Pulmonary Disease (ECOPD) are a
major problem worldwide and usually a leading cause for hospitalizations and in
some cases, indication for invasive mechanical ventilation (IMV). OBJECTIVE: The
aim of this study was to determine the length of stay in hospital and outcome of
ECOPD patients. We compared the length of hospital stay in the medical ward,
intensive care unit (ICU) departments and discharges during a period of six
months. METHODS: This was an observational, longitudinal prospective study of 242
COPD patients that were admitted with COPD exacerbation. In each patient, acute
physiology and chronic health evaluation (APACHE) II score and serial arterial
blood gases (ABG) were measured upon and during admission. RESULTS: Eighty per
cent (194) of 242 COPD patients were admitted to the medical department and most
of them were discharged within five days. Forty-eight needed IMV and stayed in
hospital more than ten days; overall mortality rate was about 5%. CONCLUSION:
Most of the hospitalized patients with COPD exacerbation (60%) were discharged
within five days, 20% needed IMV and stayed in hospital more than ten days.
PMID- 25117390
TI - Hypothalamic-pituitary-ovarian Axis in Thyroid Dysfunction.
AB - BACKGROUND: It has been established that thyroid dysfunction causes impairment of
reproductive function. However, laboratory and human studies that associated this
with female reproductive hormones are conflicting and data reporting the effects
of thyroid dysfunction on reproductive organs are insufficient. AIM: This study
investigated the effect of experimental hypothyroidism and hyperthyroidism on
hypothalamic-pituitary-ovarian axis and reproductive organs morphometry and
histology in female rats. METHODS: Laboratory animals were randomized into one of
the three groups: control, carbimazole-induced hypothyroidism and levothyroxine
induced hyperthyroidism. RESULTS: Organ morphometry and serum follicle
stimulating hormone (FSH) were statistically comparable across all groups. Serum
progesterone increased in hypothyroid rats but was reduced in hyperthyroid rats
when compared with the control (p < 0.05). Body weight gain, serum luteinizing
hormone and oestradiol were significantly reduced in both hypothyroid and
hyperthyroid states when compared to the control. Hypothyroidism and
hyperthyroidism also led to alterations in organ cytoarchitecture. CONCLUSION:
Findings from this study suggest that impairment of reproductive function
associated with thyroid dysfunction is attendant with derangement of hormonal
milieu and alteration in reproductive organs cytoarchitecture. Luteinizing
hormone and oestradiol are implicated.
PMID- 25117392
TI - Evaluation of incidental thyroid cancer in patients with thyroidectomy.
AB - OBJECTIVES: Variations such as communications between median nerve and
musculocutaneous nerve or in their abnormal branching pattern constitute a major
concern in clinical and surgical field. Knowledge of these variations not only
provides the clinician with a proper interpretation of the case, but also
minimizes the complication in surgical approaches in this region. METHOD: We
examined 50 isolated upper limbs to investigate the possible incidences of
various types of communications between these two neighbouring peripheral nerves.
RESULT: Twenty-eight per cent of limbs were found to have communication between
these two nerves. When categorized according to Venieratos and Anagnostopoulou's
classification method, 11 out of 14 cases (79%) showed type I communications, two
out of 14 (14%) showed type II and the remaining one (7%) showed type III
communication pattern. CONCLUSION: Prior knowledge of communications between
these two neighbouring nerves, both in terms of their incidences and pattern of
communications, may be of considerable significance to neurologists and
orthopaedicians in dealing with nerve entrapment syndromes in the upper limb of
patients.
PMID- 25117393
TI - A plea for more umbilical stomas in paediatric surgical practice.
PMID- 25117394
TI - Incontinentia Pigmenti in 22-month Old Afro-Caribbean Fraternal Twin Girls. A
Case Report.
AB - Incontinentia pigmenti is a rare X-linked dominant condition characterized by
cutaneous, neural, ocular and dental manifestations. The condition has mainly
been reported in Caucasian females. The aim of this case report is to highlight
the clinical presentation in Afro-Caribbean twin girls. The girls demonstrated
abnormal hair distribution, pigmented limbs and torso, small conical or missing
teeth with delayed dental eruption.
PMID- 25117395
TI - Deep lobe parotid abscess with facial nerve palsy: a case report.
AB - Acute suppurative sialadenitis mostly occurs in the parotid gland, while parotid
abscesses principally arise in the superficial lobe. However, facial nerve palsy,
secondary to parotid abscess, is rare. Predisposing factors for the ductally
ascending infection are dehydration, xerogenic drugs and salivary gland diseases
associated with ductal obstruction or reduced saliva secretion. Obstruction of
Stensen's duct and diminished production of saliva are regarded as the promoting
factors. Painful swelling of the preauricular region and cheek is the most
familiar symptom of acute suppurative parotitis. The most common pathogens
associated with acute bacterial infection are Staphylococcus aureus and
anaerobes. We report a rare case of deep lobe parotid abscess with facial nerve
palsy. Aside from adequate fluid hydration, good oral hygiene and treatment with
empiric parenteral antibiotics, surgical treatment with drainage can provide a
remedy for this disease.
PMID- 25117396
TI - Metastatic tumour of spermatic cords, epididymis and seminiferous duct from
gastric carcinoma.
AB - Metastatic tumour of spermatic cords, epididymis and seminiferous duct from
gastric carcinoma has been recently reported but rarely seen.A case of metastatic
tumour from gastric carcinoma in a 50-year old man is herein reported. The
initial diagnosis was thickening of both spermatic cords. Needle biopsy of the
spermatic cord, testicle and epididymis was performed. Pathological findings
showed a gastric signet ring cell carcinoma. Thus, double radical orchiectomy was
performed and metastatic signet ring cell carcinoma of the spermatic cord and
testis was diagnosed through histological xamination and immunohistochemistry.
Physicians should be aware that gastric carcinoma is one of the possibilities for
metastasis to the seminal duct.
PMID- 25117397
TI - Treatment with acarbose in severe hypoglycaemia due to late dumping syndrome.
AB - Dumping syndrome is a serious complication that may occur after gastric surgery
in approximately 10% of patients in the 1990s. With the increasing number of
patients undergoing bariatric surgery, the incidence of dumping syndrome is
likely to increase in recent years. It is necessary for clinicians to recognize
the syndrome and master its management. We present a case of recurrent loss of
consciousness, which was finally accurately diagnosed as late dumping syndrome
twelve years after subtotal gastrectomy and successfully treated with acarbose. A
66-year old lean male was found unconscious repeatedly within one year, oral
glucose tolerance tests performed before and after acarbose treatment verified
the diagnosis of late dumping syndrome. Hypoglycaemia can damage the body in
acute and chronic form. Acarbose can be used as a successful treatment modality
for reactive hypoglycaemia due to late dumping syndrome by influencing the
release of hormone.
PMID- 25117398
TI - Recurrent primary hydatid disease of the tibia.
AB - Hydatid disease is caused by a cestode, Echinococcus. Its intermediate hosts are
herbivores but humans can be accidental hosts. Hydatid disease is endemic in some
parts of America, Australia, the Mediterranean region, Central Asia, and Central
and Eastern Europe. The organs most frequently affected by Echinococcus are the
liver and the lungs. Primary involvement of the skeleton is rare. Cases have been
reported in the vertebrae, pelvis, humerus and femur. The location of hydatid
cysts in the tibia is rarely described in the medical literature. We, herein,
report a case of primary hydatid cyst of the tibia presenting with a pathologic
fracture simulating benign bone cystic lesion. The diagnosis of hydatid bone
disease was not suspected preoperatively. This case emphasizes the importance of
considering hydatid disease in the differential diagnosis of cystic bone lesions,
especially in individuals coming from regions where the disease is endemic.
PMID- 25117399
TI - Chronic renal disease and reversible posterior leukoencephalopathy syndrome after
liver transplantation.
AB - This is a case report of a patient who developed chronic renal dysfunction and
neurologic emergency with multiple cranial lesions after liver transplantation.
Immune-complex glomerulonephritis was confirmed on the basis of histopathologic
evaluation of the renal biopsy. According to clinical features and brain magnetic
resonance imaging follow-up, neuroradiographic atypical reversible posterior
leukoencephalopathy syndrome (RPLS) was finally diagnosed.
PMID- 25117400
TI - Effects of the Etna uphill ultramarathon on energy cost and mechanics of running.
AB - PURPOSE: To investigate the effects of an extreme uphill marathon on the
mechanical parameters that are likely to affect the energy cost of running (Cr).
METHODS: Eleven runners (27-59 y) participated in the Etna SuperMarathon (43 km,
0-3063 m above sea level). Anthropometric characteristics, maximal explosive
power of the lower limb (Pmax), and maximal oxygen uptake were determined before
the competition. In addition, before and immediately after the race, Cr, contact
(tc) and aerial (ta) times, step frequency (f), and running velocity were
measured at constant self-selected speed. Then, peak vertical ground-reaction
force (Fmax), vertical downward displacement of the center of mass (Deltaz), leg
length change (DeltaL), and vertical (kvert) and leg (kleg) stiffness were
calculated. RESULTS: A direct relationship between Cr, measured before the race,
and race time was shown (r=.61, P<.001). Cr increased significantly at the end of
the race by 8.7%. Immediately after the race, the subjects showed significantly
lower ta (-58.6%), f (-11.3%), Fmax (-17.6%), kvert (-45.6%), and kleg (-42.3%)
and higher tc (+28.6%), Deltaz (+52.9%), and DeltaL (+44.5%) than before the
race. The increase of Cr was associated with a decrement in Fmax (r=-.45), kvert
(r=-.44), and kleg (r=-.51). Finally, an inverse relationship between Pmax
measured before the race and DeltaCr during race was found (r=-.52). CONCLUSIONS:
Lower Cr was related with better performance, and athletes characterized by the
greater Pmax showed lower increases in Cr during the race. This suggests that
specific power training of the lower limbs may lead to better performance in
ultraendurance running competition.
PMID- 25117401
TI - Development of casein microgels from cross-linking of casein micelles by genipin.
AB - Casein micelles are porous colloidal particles, constituted of casein molecules,
water, and minerals. The vulnerability of the supramolecular structure of casein
micelles face to changes in the environmental conditions restrains their
applications in other domains besides food. Thus, redesigning casein micelles is
a challenge to create new functionalities for these biosourced particles. The
objective of this work was to create stable casein microgels from casein micelles
using a natural cross-linker, named genipin. Suspensions of purified casein
micelles (25 g L(-1)) were mixed with genipin solutions to have final
concentrations of 5, 10, and 20 mM genipin. Covalently linked casein microgels
were formed via cross-linking of lysyl and arginyl residues of casein molecules.
The reacted products exhibited blue color. The cross-linking reaction induced
gradual changes on the colloidal properties of the particles. The casein
microgels were smaller and more negatively charged and presented smoother
surfaces than casein micelles. These results were explained based on the cross
linking of free NH2 present in an external layer of kappa-casein. Light
scattering and rheological measurements showed that the reaction between genipin
and casein molecules was intramicellar, as one single population of particles was
observed and the values of viscosity (and, consequently, the volume fraction of
the particles) were reduced. Contrary to the casein micelles, the casein
microgels were resistant to the presence of dissociating agents, e.g., citrate
(calcium chelating) and urea, but swelled as a consequence of internal
electrostatic repulsion and the disruption of hydrophobic interactions between
protein chains. The casein microgels did not dissociate at the air-solution
interface and formed solid-like interfaces rather than a viscoelastic gel. The
potential use of casein microgels as adaptable nanocarriers is proposed in the
article.
PMID- 25117402
TI - DNA Commission of the International Society for Forensic Genetics: revised and
extended guidelines for mitochondrial DNA typing.
AB - The DNA Commission of the International Society of Forensic Genetics (ISFG)
regularly publishes guidelines and recommendations concerning the application of
DNA polymorphisms to the question of human identification. Previous
recommendations published in 2000 addressed the analysis and interpretation of
mitochondrial DNA (mtDNA) in forensic casework. While the foundations set forth
in the earlier recommendations still apply, new approaches to the quality
control, alignment and nomenclature of mitochondrial sequences, as well as the
establishment of mtDNA reference population databases, have been developed. Here,
we describe these developments and discuss their application to both mtDNA
casework and mtDNA reference population databasing applications. While the
generation of mtDNA for forensic casework has always been guided by specific
standards, it is now well-established that data of the same quality are required
for the mtDNA reference population data used to assess the statistical weight of
the evidence. As a result, we introduce guidelines regarding sequence generation,
as well as quality control measures based on the known worldwide mtDNA phylogeny,
that can be applied to ensure the highest quality population data possible. For
both casework and reference population databasing applications, the alignment and
nomenclature of haplotypes is revised here and the phylogenetic alignment
proffered as acceptable standard. In addition, the interpretation of heteroplasmy
in the forensic context is updated, and the utility of alignment-free database
searches for unbiased probability estimates is highlighted. Finally, we discuss
statistical issues and define minimal standards for mtDNA database searches.
PMID- 25117403
TI - Population data of 12 X-chromosome STR loci in Yanbian Korean samples from China.
PMID- 25117405
TI - Thyrostimulin deficiency does not alter peripheral responses to acute
inflammation-induced nonthyroidal illness.
AB - Thyrostimulin, a putative glycoprotein hormone, comprises the subunits GPA2 and
GPB5 and activates the TSH receptor (TSHR). The observation that proinflammatory
cytokines stimulate GPB5 transcription suggested a role for thyrostimulin in the
pathogenesis of nonthyroidal illness syndrome (NTIS). In the present study, we
induced acute inflammation by LPS administration to GPB5(-/-) and WT mice to
evaluate the role of thyrostimulin in peripheral thyroid hormone metabolism
during NTIS. In addition to serum thyroid hormone concentrations, we studied mRNA
expression and activity of deiodinase types I, II, and III (D1, D2, and D3) in
peripheral T3 target tissues, including liver, muscle, and white and brown
adipose tissue (WAT and BAT), of which the latter three express the TSHR. LPS
decreased serum free (f)T4 and fT3 indexes to a similar extent in GPB5(-/-) and
WT mice. Serum reverse (r)T3 did not change following LPS administration. LPS
also induced significant alterations in tissue D1, D2, and D3 mRNA and activity
levels, but only the LPS-induced increase in WAT D2 mRNA expression differed
between GPB5(-/-) and WT mice. In conclusion, lacking GPB5 during acute illness
does not affect the LPS-induced decrease of serum thyroid hormones while
resulting in subtle changes in tissue D2 expression that are unlikely to be
mediated via the TSHR.
PMID- 25117404
TI - Vasodilator-stimulated phosphoprotein protects against vascular inflammation and
insulin resistance.
AB - Among the pleotropic effects of endothelial nitric oxide (NO) is protection
against vascular inflammation during high-fat diet (HFD) feeding. The current
work investigated the role of the enzyme vasodilatory-stimulated phosphoprotein
(VASP) as a downstream mediator of the anti-inflammatory effect of NO signaling
in vascular tissue. Relative to mice fed a low-fat diet (LFD), levels of VASP
Ser(239) phosphorylation, a marker of VASP activation, were dramatically reduced
in aortic tissue of mice with obesity induced by consuming a HFD. As reported
previously, the effect of the HFD was associated with increased aortic
inflammation, as measured by increased NF-kappaB-dependent gene expression, and
reduced vascular insulin sensitivity (including insulin-stimulated
phosphorylation of eNOS and Akt). These effects of the HFD were recapitulated by
VASP knockout, implying a physiological role for VASP to constrain inflammatory
signaling and thereby maintain vascular insulin sensitivity. Conversely,
overexpression of VASP in endothelial cells blocked inflammation and insulin
resistance induced by palmitate. The finding that transplantation of bone marrow
from VASP-deficient donors into normal recipients does not recapitulate the
vascular effects of whole body VASP deficiency suggests that the protective
effects of this enzyme are not mediated in immune or other bone marrow-derived
cells. These studies implicate VASP as a downstream mediator of the NO/cGMP
pathway that is both necessary and sufficient to protect against vascular
inflammation and insulin resistance. As such, this work identifies VASP as a
potential therapeutic target in the treatment of obesity-related vascular
dysfunction.
PMID- 25117406
TI - Role of capsaicin-sensitive peripheral sensory neurons in anorexic responses to
intravenous infusions of cholecystokinin, peptide YY-(3-36), and glucagon-like
peptide-1 in rats.
AB - Cholecystokinin (CCK)-induced suppression of feeding is mediated by vagal sensory
neurons that are destroyed by the neurotoxin capsaicin (CAP). Here we determined
whether CAP-sensitive neurons mediate anorexic responses to intravenous infusions
of gut hormones peptide YY-(3-36) [PYY-(3-36)] and glucagon-like peptide-1 (GLP
1). Rats received three intraperitoneal injections of CAP or vehicle (VEH) in 24
h. After recovery, non-food-deprived rats received at dark onset a 3-h
intravenous infusion of CCK-8 (5, 17 pmol.kg-1.min-1), PYY-(3-36) (5, 17, 50
pmol.kg-1.min-1), or GLP-1 (17, 50 pmol.kg-1.min-1). CCK-8 was much less
effective in reducing food intake in CAP vs. VEH rats. CCK-8 at 5 and 17 pmol.kg
1.min-1 reduced food intake during the 3-h infusion period by 39 and 71% in VEH
rats and 7 and 18% in CAP rats. In contrast, PYY-(3-36) and GLP-1 were similarly
effective in reducing food intake in VEH and CAP rats. PYY-(3-36) at 5, 17, and
50 pmol.kg-1.min-1 reduced food intake during the 3-h infusion period by 15, 33,
and 70% in VEH rats and 13, 30, and 33% in CAP rats. GLP-1 at 17 and 50 pmol.kg
1.min-1 reduced food intake during the 3-h infusion period by 48 and 60% in VEH
rats and 30 and 52% in CAP rats. These results suggest that anorexic responses to
PYY-(3-36) and GLP-1 are not primarily mediated by the CAP-sensitive peripheral
sensory neurons (presumably vagal) that mediate CCK-8-induced anorexia.
PMID- 25117407
TI - Stimulation of glucagon-like peptide-1 receptor through exendin-4 preserves
myocardial performance and prevents cardiac remodeling in infarcted myocardium.
AB - We have demonstrated that GLP-1 improved myocardial functional recovery in acute
myocardial ischemic injury. However, whether stimulation of the GLP-1 receptor
(GLP-1R) with exendin-4, a selective GLP-1R agonist, could initiate a protective
effect in the heart remains to be determined. Mouse myocardial infarction (MI)
was created by ligation of the left descending artery. After 48 h of MI, animals
were divided into the following groups (n = 5-7/group): 1) sham (animals that
underwent thoracotomy without ligation), 2) MI [animals that underwent MI and
received a daily dose of intraperitoneal injection (ip) of saline]; and 3) MI +
exendin-4 [infarcted mice that received injections of exendin-4 (0.1 mg/kg ip)].
Two weeks later, cardiac function was assessed by echocardiography and an
isovolumetrically perfused heart. Compared with control MI hearts, stimulation of
GLP-1R improved cardiac function, which was associated with attenuation of
myocardial hypertrophy, the mitigation of interstitial fibrosis, and an increase
in survival rate in post-MI hearts. Furthermore, H9c2 cardiomyoblasts were
preconditioned with exendin-4 at a dose of 100 nmol/l and then subjected to
hydrogen peroxide exposure at concentrations of 50 and 100 MUmol/l. The exendin-4
treatment decreased lactate dehydrogenase leakage and increased cell survival.
Notably, this event was also associated with the reduction of cleaved caspase-3
and caspase-9 and attenuation of reactive oxygen species production. Exendin-4
treatments improved mitochondrial respiration and suppressed the opening of
mitochondrial permeability transition pore and protected mitochondria function.
Our results indicate that GLP-1R serves as a novel approach to eliciting
cardioprotection and mitigating oxidative stress-induced injury.
PMID- 25117408
TI - Hepatic portal vein denervation impairs oral glucose tolerance but not
exenatide's effect on glycemia.
AB - The hepatoportal area is an important glucohomeostatic metabolic sensor, sensing
hypoglycemia, hyperglycemia, and hormones such as glucagon-like peptide-1 (GLP
1). We have reported previously that activation of hepatoportal sensors by
intraportal infusion of glucose and GLP-1 or by subcutaneous administration of
GLP-1 receptor activator exenatide and of intraportal glucose improved glycemia
independent of corresponding changes in pancreatic hormones. It is not clear
whether this effect is mediated via the portal vein (PV) or by direct action on
the liver itself. To test whether receptors in the PV mediate exenatide's
beneficial effect on glucose tolerance, we performed 1) paired oral glucose
tolerance tests (OGTT) with and without exenatide and 2) intravenous glucose
tolerance tests before and after PV denervation in canines. Denervation of the
portal vein affected oral glucose tolerance; post-denervation (POST-DEN) OGTT
glucose and insulin AUC were 50% higher than before denervation (P = 0.01).
However, portal denervation did not impair exenatide's effect to improve oral
glucose tolerance (exenatide effect: 48 +/- 12 mmol.l-1.min before vs. 64 +/- 26
mmol.l-1.min after, P = 0.67). There were no changes in insulin sensitivity or
secretion during IVGTTs. Portal vein sensing might play a role in controlling
oral glucose tolerance during physiological conditions but not in pharmacological
activation of GLP-1 receptors by exenatide.
PMID- 25117410
TI - Role of STAT5 and epigenetics in lactation-associated upregulation of multidrug
transporter ABCG2 in the mammary gland.
AB - The multidrug resistance efflux transporter ATP-binding cassette subfamily G
member 2 (ABCG2) is not only overexpressed in certain drug-resistant cancers but
is also highly expressed in the mammary gland during lactation, carrying
xenobiotics and nutrients into milk. We sought to investigate the molecular
mechanisms involved in the upregulation of ABCG2 during lactation. Expression
profiling of different mouse Abcg2 mRNA isoforms (E1a, E1b, and E1c) revealed
that E1b is predominantly expressed and induced in the lactating mouse mammary
gland. Despite this induction, analyses of CpG methylation status and published
ChIP-seq datasets reveal that E1b promoter sequences in the virgin gland are
already hypomethylated and marked with the open chromatin histone mark H3K4me2.
Using a forced-weaning model to shut down lactation, we found that within 24 h
there was a significant reduction in Abcg2 mRNA expression and a loss of signal
transducer and activator of transcription-5 (STAT5) occupancy at the mouse Abcg2
gene. Luciferase reporter assays further showed that some of these STAT5-binding
regions that contained interferon-gamma-activated sequence (GAS) motifs function
as an enhancer after prolactin treatment. We conclude that Abcg2 is already
poised for expression in the virgin mammary gland and that STAT5 plays an
important role in Abcg2 expression during lactation.
PMID- 25117409
TI - Partial blockade of nicotinic acetylcholine receptors improves the
counterregulatory response to hypoglycemia in recurrently hypoglycemic rats.
AB - Recurrent exposure to hypoglycemia can impair the normal counterregulatory
hormonal responses that guard against hypoglycemia, leading to hypoglycemia
unawareness. This pathological condition known as hypoglycemia-associated
autonomic failure (HAAF) is the main adverse consequence that prevents
individuals with type 1 diabetes mellitus from attaining the long-term health
benefits of tight glycemic control. The underlying molecular mechanisms
responsible for the progressive loss of the epinephrine response to subsequent
bouts of hypoglycemia, a hallmark sign of HAAF, are largely unknown. Normally,
hypoglycemia triggers both the release and biosynthesis of epinephrine through
activation of nicotinic acetylcholine receptors (nAChR) on the adrenal glands. We
hypothesize that excessive cholinergic stimulation may contribute to impaired
counterregulation. Here, we tested whether administration of the nAChR partial
agonist cytisine to reduce postganglionic synaptic activity can preserve the
counterregulatory hormone responses in an animal model of HAAF. Compared with
nicotine, cytisine has limited efficacy to activate nAChRs and stimulate
epinephrine release and synthesis. We evaluated adrenal catecholamine production
and secretion in nondiabetic rats subjected to two daily episodes of hypoglycemia
for 3 days, followed by a hyperinsulinemic hypoglycemic clamp on day 4. Recurrent
hypoglycemia decreased epinephrine responses, and this was associated with
suppressed TH mRNA induction (a measure of adrenal catecholamine synthetic
capacity). Treatment with cytisine improved glucagon responses as well as
epinephrine release and production in recurrently hypoglycemic animals. These
data suggest that pharmacological manipulation of ganglionic nAChRs may be
promising as a translational adjunctive therapy to avoid HAAF in type 1 diabetes
mellitus.
PMID- 25117411
TI - The effect of estrogen on bone requires ERalpha in nonhematopoietic cells but is
enhanced by ERalpha in hematopoietic cells.
AB - The effects of estrogen on bone are mediated mainly via estrogen receptor
(ER)alpha. ERalpha in osteoclasts (hematopoietic origin) is involved in the
trabecular bone-sparing effects of estrogen, but conflicting data are reported on
the role of ERalpha in osteoblast lineage cells (nonhematopoietic origin) for
bone metabolism. Because Cre-mediated cell-specific gene inactivation used in
previous studies might be confounded by nonspecific and/or incomplete cell
specific ERalpha deletion, we herein used an alternative approach to determine
the relative importance of ERalpha in hematopoietic (HC) and nonhematopoietic
cells (NHC) for bone mass. Chimeric mice with selective inactivation of ERalpha
in HC or NHC were created by bone marrow transplantations of wild-type (WT) and
ERalpha-knockout (ERalpha(-/-)) mice. Estradiol treatment increased both
trabecular and cortical bone mass in ovariectomized WT/WT (defined as
recipient/donor) and WT/ERalpha(-/-) mice but not in ERalpha(-/-)/WT or ERalpha(
/-)/ERalpha(-/-) mice. However, estradiol effects on both bone compartments were
reduced (~50%) in WT/ERalpha(-/-) mice compared with WT/WT mice. The effects of
estradiol on fat mass and B lymphopoiesis required ERalpha specifically in NHC
and HC, respectively. In conclusion, ERalpha in NHC is required for the effects
of estrogen on both trabecular and cortical bone, but these effects are enhanced
by ERalpha in HC.
PMID- 25117413
TI - Interventions for congenital talipes equinovarus (clubfoot).
AB - BACKGROUND: Congenital talipes equinovarus (CTEV), which is also known as
clubfoot, is a common congenital orthopaedic condition characterised by an
excessively turned in foot (equinovarus) and high medial longitudinal arch
(cavus). If left untreated it can result in long-term disability, deformity and
pain. Interventions can be conservative (such as splinting or stretching) or
surgical. The review was first published in 2012 and we reviewed new searches in
2013 (update published 2014). OBJECTIVES: To evaluate the effectiveness of
interventions for CTEV. SEARCH METHODS: On 29 April 2013, we searched CENTRAL
(2013, Issue 3 in The Cochrane Library), MEDLINE (January 1966 to April 2013),
EMBASE (January 1980 to April 2013), CINAHL Plus (January 1937 to April 2013),
AMED (1985 to April 2013), and the Physiotherapy Evidence Database (PEDro to
April 2013). We also searched for ongoing trials in the WHO International
Clinical Trials Registry Platform (2006 to July 2013) and ClinicalTrials.gov (to
November 2013). We checked the references of included studies. We searched
NHSEED, DARE and HTA for information for inclusion in the Discussion. SELECTION
CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs evaluating
interventions for CTEV. Participants were people of all ages with CTEV of either
one or both feet. DATA COLLECTION AND ANALYSIS: Two authors independently
assessed risk of bias in included trials and extracted the data. We contacted
authors of included trials for missing information. We collected adverse event
information from trials when it was available. MAIN RESULTS: We identified 14
trials in which there were 607 participants; one of the trials was newly included
at this 2014 update. The use of different outcome measures prevented pooling of
data for meta-analysis even when interventions and participants were comparable.
All trials displayed bias in four or more areas. One trial reported on the
primary outcome of function, though raw data were not available to be analysed.
We were able to analyse data on foot alignment (Pirani score), a secondary
outcome, from three trials. Two of the trials involved participants at initial
presentation. One reported that the Ponseti technique significantly improved foot
alignment compared to the Kite technique. After 10 weeks of serial casting, the
average total Pirani score of the Ponseti group was 1.15 (95% confidence interval
(CI) 0.98 to 1.32) lower than that of the Kite group. The second trial found the
Ponseti technique to be superior to a traditional technique, with average total
Pirani scores of the Ponseti participants 1.50 lower (95% CI 0.72 to 2.28) after
serial casting and Achilles tenotomy. A trial in which the type of presentation
was not reported found no difference between an accelerated Ponseti or standard
Ponseti treatment. At the end of serial casting, the average total Pirani scores
in the standard group were 0.31 lower (95% CI -0.40 to 1.02) than the accelerated
group. Two trials in initial cases found relapse following Ponseti treatment was
more likely to be corrected with further serial casting compared to the Kite
groups which more often required major surgery (risk difference 25% and 50%).
There is a lack of evidence for different plaster casting products, the addition
of botulinum toxin A during the Ponseti technique, different types of major foot
surgery, continuous passive motion treatment following major foot surgery, or
treatment of relapsed or neglected cases of CTEV. Most trials did not report on
adverse events. In trials evaluating serial casting techniques, adverse events
included cast slippage (needing replacement), plaster sores (pressure areas) and
skin irritation. Adverse events following surgical procedures included infection
and the need for skin grafting. AUTHORS' CONCLUSIONS: From the limited evidence
available, the Ponseti technique produced significantly better short-term foot
alignment compared to the Kite technique and compared to a traditional technique.
The quality of this evidence was low to very low. An accelerated Ponseti
technique may be as effective as a standard technique, according to moderate
quality evidence. Relapse following the Kite technique more often led to major
surgery compared to relapse following the Ponseti technique. We could draw no
conclusions from other included trials because of the limited use of validated
outcome measures and lack of available raw data. Future randomised controlled
trials should address these issues.
PMID- 25117414
TI - Melatonin Can Be Used to Treat Childhood Breath-Holding Spells.
PMID- 25117412
TI - Differential effects of c-Src and c-Yes on the endocytic vesicle-mediated
trafficking events at the Sertoli cell blood-testis barrier: an in vitro study.
AB - The blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in
the mammalian body. However, it undergoes cyclic restructuring during the
epithelial cycle of spermatogenesis in which the "old" BTB located above the
preleptotene spermatocytes being transported across the immunological barrier is
"disassembled," whereas the "new" BTB found behind these germ cells is rapidly
"reassembled," i.e., mediated by endocytic vesicle-mediated protein trafficking
events. Thus, the immunological barrier is maintained when preleptotene
spermatocytes connected in clones via intercellular bridges are transported
across the BTB. Yet the underlying mechanism(s) in particular the involving
regulatory molecules that coordinate these events remains unknown. We
hypothesized that c-Src and c-Yes might work in contrasting roles in endocytic
vesicle-mediated trafficking, serving as molecular switches, to effectively
disassemble and reassemble the old and the new BTB, respectively, to facilitate
preleptotene spermatocyte transport across the BTB. Following siRNA-mediated
specific knockdown of c-Src or c-Yes in Sertoli cells, we utilized biochemical
assays to assess the changes in protein endocytosis, recycling, degradation and
phagocytosis. c-Yes was found to promote endocytosed integral membrane BTB
proteins to the pathway of transcytosis and recycling so that internalized
proteins could be effectively used to assemble new BTB from the disassembling old
BTB, whereas c-Src promotes endocytosed Sertoli cell BTB proteins to endosome
mediated protein degradation for the degeneration of the old BTB. By using
fluorescence beads mimicking apoptotic germ cells, Sertoli cells were found to
engulf beads via c-Src-mediated phagocytosis. A hypothetical model that serves as
the framework for future investigation is thus proposed.
PMID- 25117415
TI - Serum N-Terminal Pro-B-Type Natriuretic Peptide (NTproBNP) Levels Are Elevated
During the Acute Phase of Acute Encephalopathy-Associated Virus Infection.
AB - Acute virus-associated encephalopathy induces seizures. Serum N-terminal pro-B
type natriuretic peptide (NTproBNP) levels are elevated following febrile and
afebrile seizures. However, the role of NTproBNP in acute virus-associated
encephalopathy pathology is unknown. We enrolled 10 patients with acute virus
associated encephalopathy and convulsions (E group: 7 boys, 3 girls; median age,
3.10 +/- 1.92 years) and 130 patients with febrile seizure (FS group: 80 boys, 50
girls; median age, 3.23 +/- 2.44 years). The E group had significantly higher
NTproBNP levels (345 +/- 141 pg/mL) compared with the FS group (166 +/- 228
pg/mL) (P < .0005). Furthermore, subjects with prolonged seizure within the E
group had significantly higher NTproBNP levels (303 +/- 107 pg/mL) compared with
subjects with prolonged seizure within the FS group (134 +/- 100 pg/mL) (P <
.005). Our findings suggest that serum NTproBNP levels are increased during the
acute phase of acute virus-associated encephalopathy associated with convulsion.
PMID- 25117416
TI - Sturge Weber-Like Gyral Calcification Seen in Tuberous Sclerosis Complex 1.
AB - A 10-year-old girl presented with poorly controlled epilepsy. On evaluation, she
had microcephaly, neuro-cutaneous stigmata of tuberous sclerosis complex,
profound mental retardation, and spastic hemiparesis. Computed tomography (CT)
revealed a calcified subependymal nodule and extensive left gyral calcification
of the temporal, parietal, and occipital regions with unilateral cerebral
atrophy, radiologic features usually seen in Sturge Weber syndrome. Magnetic
resonance imaging (MRI) revealed absence of tubers, enlarged choroid plexus, or
leptomeningeal angiomas, thus excluding type 3 Sturge Weber syndrome. The
genotype was a heterozygous mutation in exon 18 of the tuberous sclerosis type 1
gene (c.2293C>T p.Q765X). A comparison of previously reported 7 cases of Sturge
Weber syndrome and tuberous sclerosis complex was made. This revealed 4 actual
double phakomatoses (clinical, radiologic, or genetic phenotypes) and 3 cases
with clinical phenotype of tuberous sclerosis and gyral calcifications within
tubers simulating the radiologic picture of Sturge Weber syndrome.
PMID- 25117417
TI - Impact of rotavirus vaccine introduction on rotavirus-associated seizures and a
related possible mechanism.
AB - To determine whether clinical features of rotavirus-associated seizures have been
altered by rotavirus vaccination, we compared clinical and laboratory data of 2
groups of patients with rotavirus-associated seizures: pre- and post-vaccine
introduction groups. The seizure characteristics differed significantly between
the groups, with a lower incidence of fever at seizure onset, longer interval
between the onset of gastroenteritis and seizures, and more frequent seizures in
the postintroduction group. These characteristics may suggest that seizure
susceptibility was increased in the postintroduction group. Based on the lower
serum Cl(-) (102.1 +/- 4.1 vs 98.2 +/- 3.2 mg/dL; P < .01) and Ca(2+) levels (9.2
+/- 0.4 vs 9.0 +/- 0.3 mg/dL; P = .12) in the postintroduction group, we propose
that a change in the subjects' susceptibility to the rotavirus enterotoxin may
have played a role in increasing the seizure susceptibility in this group. Our
results suggest that a rotavirus vaccination program may modulate the
manifestations of rotavirus-associated seizures.
PMID- 25117419
TI - Evaluation of basal ganglia and thalamic inflammation in children with pediatric
autoimmune neuropsychiatric disorders associated with streptococcal infection and
tourette syndrome: a positron emission tomographic (PET) study using 11C-[R]
PK11195.
AB - We applied PET scanning with (11)C-[R]-PK11195 (PK) to evaluate neuroinflammatory
changes in basal ganglia and thalamus in children with clinically diagnosed
pediatric autoimmune neuropsychiatric disorders associated with streptococcal
infection (PANDAS) and Tourette syndrome. Seventeen children with PANDAS (mean
age: 11.4 +/- 2.6 years; 13 males), 12 with Tourette syndrome (mean age: 11.0 +/-
3.0 years; 10 males), and 15 normal adults (mean age: 28.7 +/- 7.9 years; 8
males) underwent dynamic PK PET imaging and binding potential, a measure of
ligand-TSPO receptor (expressed by activated microglia) binding, was calculated
for basal ganglia and thalamus. Binding potential values, suggesting underlying
activated microglia-mediated neuroinflammation, were found to be increased in
bilateral caudate and bilateral lentiform nucleus in the PANDAS group and in
bilateral caudate nuclei only in the Tourette syndrome group, compared to control
group. These differences in the pattern and extent of neuroinflammation also
signify a possible difference in pathophysiological etiology between PANDAS and
Tourette syndrome patients.
PMID- 25117420
TI - A 5-year-old male child with late infantile metachromatic leukodystrophy: a case
report.
AB - Metachromatic leukodystrophy is a rare disorder of myelin metabolism. This
degenerative disorder results from the accumulation of cerebroside sulfatide
within the myelin sheath of central and peripheral nervous system, due to
deficiency of aryl sulfatase A enzyme. We report a 5-year-old male child, who
presented with regression of milestones, recurrent seizures and spasticity from
second year of life. Initially neurodegenerative disorder was considered and the
case was investigated with neuroimaging and enzyme levels. Computed tomography
(CT) of the brain showed hypodensities in the corpus callosum and bilateral
periventricular and deep cerebral white matter suggestive of neurodegenerative
disorder. Subsequently, magnetic resonance imaging (MRI) of the brain was done,
which showed symmetrical hyperintensities in the periventricular white matter
with classical sparing of subcortical "U" fibers. The beta-galactosidase enzyme
activity was normal; however, the activity of aryl sulfatase A enzyme was
undetectable, confirming the diagnosis of late infantile variant of metachromatic
leukodystrophy.
PMID- 25117418
TI - Perinatal medical variables predict executive function within a sample of
preschoolers born very low birth weight.
AB - The goal was to identify perinatal predictors of early executive dysfunction in
preschoolers born very low birth weight. Fifty-seven preschoolers completed 3
executive function tasks: Dimensional Change Card Sort-Separated (inhibition,
working memory, and cognitive flexibility), Bear Dragon (inhibition and working
memory), and Gift Delay Open (inhibition). Relationships between executive
function and perinatal medical severity factors (gestational age, days on
ventilation, size for gestational age, maternal steroids, and number of
surgeries) and chronological age were investigated by multiple linear regression
and logistic regression. Different perinatal medical severity factors were
predictive of executive function tasks, with gestational age predicting Bear
Dragon and Gift Open; and number of surgeries and maternal steroids predicting
performance on Dimensional Change Card Sort-Separated. By understanding the
relationship between perinatal medical severity factors and preschool executive
outcomes, we can identify children at highest risk for future executive
dysfunction, thereby focusing targeted early intervention services.
PMID- 25117421
TI - Cluster stability as a new method to assess changes in performance and its
determinant factors over a season in young swimmers.
AB - PURPOSE: To apply a new method to identify, classify, and follow up young
swimmers based on their performance and its determinant factors over a season and
analyze the swimmers' stability over a competitive season with that method.
METHODS: Fifteen boys and 18 girls (11.8+/-0.7 y) part of a national talent
identification scheme were evaluated at 3 different moments of a competitive
season. Performance (ie, official 100-m freestyle race time), arm span, chest
perimeter, stroke length, swimming velocity, speed fluctuation, coefficient of
active drag, propelling efficiency, and stroke index were selected as variables.
Hierarchical and k-means cluster analysis were computed. RESULTS: Data suggested
a 3-cluster solution, splitting the swimmers according to their performance in
all 3 moments. Cluster 1 was related to better performances (talented swimmers),
cluster 2 to poor performances (nonproficient swimmers), and cluster 3 to average
performance (proficient swimmers) in all moments. Stepwise discriminant analysis
revealed that 100%, 94%, and 85% of original groups were correctly classified for
the 1st, 2nd, and 3rd evaluation moments, respectively (0.11<=Lambda<=0.80;
5.64<=chi2<=63.40; 0.001
95%. Our results demonstrate the
suitability of orbitally-shaken bioreactors for the scaled-up cultivation of
plant cell suspension cultures and provide a strategy for the efficient
purification of antibodies from the BY-2 culture medium.
PMID- 25117429
TI - The relationship of training load to physical-capacity changes during
international tours in high-performance junior tennis players.
AB - PURPOSE: Given the travel that punctuates junior tennis development, an
understanding of the changes in fitness owing to touring and the association
between training loads (TLs) and fitness on return is vital. The authors
investigated physical-capacity changes from pretour to posttour, determining if
those changes were related to the TL of athletes on tour. METHODS: Thirty junior
athletes completed fitness testing before and after 4-wk tours. Testing included
double-leg countermovement jump (CMJ), dominant single-leg and nondominant single
leg CMJ, speed (5, 10, 20 m), modified 5-0-5 agility (left and right), 10 * 20-m
repeated-sprint ability (RSA), and multistage fitness tests. Repeated-measures
ANOVAs determined physical-capacity change, with effect-size analysis
establishing the magnitude of change. To avoid regression toward the mean, a 1/3
split technique was implemented for comparative analysis (high to low TLs).
RESULTS: Moderate effects (d=0.50-0.70) for reductions of up to 3.6% in 5-, 10-,
and 20-m speeds were observed. However, all remaining changes were only of
trivial to small magnitude (d<0.40). Closer analysis of the interaction between
TL and physical capacities (1/3-split) revealed that subjects who completed the
greatest amount of total and tennis TL returned with a greater decline in speed
and aerobic capacities (d>0.80). Furthermore, it was observed that match load
dictates on- and off-court TL, with an increase in matches won understandably
stunting exposure to off-court TL. CONCLUSIONS: Specific training should be
prescribed on tour to maintain speed characteristics over a 4-wk international
tour. On-tour training schedules should be carefully monitored to maximize
specific TL exposure after losses on tour.
PMID- 25117426
TI - CYP3A5 genotype impacts maraviroc concentrations in healthy volunteers.
AB - CYP3A5 plays a prominent role in the metabolism of maraviroc, an approved drug
for human immunodeficiency virus (HIV)-1 treatment and a candidate for HIV-1
prevention. We studied the effect of the CYP3A5 genotype on pharmacokinetics of
maraviroc and a primary CYP3A5-dependent metabolite of maraviroc denoted as
metabolite 1 (M1). Volunteers were screened for health status and CYP3A5 genotype
(wild-type allele *1 and dysfunctional alleles *2, *3, *6, and *7) to obtain 24
evaluable subjects in three groups (n = 8 each): homozygous dysfunctional (two
dysfunctional alleles), heterozygous (one *1 allele and one dysfunctional
allele), and homozygous wild-type (two *1 alleles). Subjects received 300 mg
maraviroc orally followed by blood collection for 32 hours. The homozygous wild
type group exhibited lower mean plasma maraviroc concentrations at almost all
sampling times. The median (interquartile range) maraviroc area under the plasma
concentration-time curves from time 0 to infinity (AUC0-inf) were 2099 (1422
2568) ng?h/ml, 1761 (931-2640) ng?h/ml, and 1238 (1065-1407) ng?h/ml for the
homozygous dysfunctional, heterozygous, and homozygous wild-type groups,
respectively. The homozygous wild-type group had 41% lower maraviroc AUC0-inf and
66% higher apparent clearance compared with the homozygous dysfunctional group (P
= 0.02). The AUC0-inf ratios of maraviroc to M1 in heterozygous and homozygous
wild-type subjects were lower by 51 and 64% relative to the homozygous
dysfunctional group, respectively (P < 0.001). In conclusion, the lower maraviroc
concentrations in the homozygous wild-type group indicate that maraviroc may be
underdosed in people homozygous for the CYP3A5*1 allele, including almost one
half of African Americans.
PMID- 25117430
TI - Draft genome sequence of Rhodomicrobium udaipurense JA643T with special reference
to hopanoid biosynthesis.
AB - Hopanoids are present in vast amounts as integral components of bacteria and
plants with their primary function to strengthen rigidity of the plasma membrane.
To establish their roles more precisely, we conducted sequencing of the whole
genome of Rhodomicrobium udaipurense JA643(T) isolated from a fresh water stream
of Udaipur in Himachal Pradesh, India, by using the Illumina HiSeq pair end
chemistry of 2 * 100 bp platform. Determined genome showed a high degree of
similarity to the genome of R. vannielii ATCC17100(T) and the 13.7 million reads
generated a sequence of 3,649,277 bp possessing 3,611 putative genes. The genomic
data were subsequently investigated with respect to genes involved in various
features. The machinery required for the degradation of aromatic compounds and
resistance to solvents as well as all that required for photosynthesis are
present in this organism. Also, through extensive functional annotation, 18 genes
involved in the biosynthesis of hopanoids are predicted, namely those responsible
for the synthesis of diploptene, diplopterol, adenosylhopane, ribosylhopane,
aminobacteriohopanetriol, glycosyl group containing hopanoids and unsaturated
hopanoids. The hopanoid biosynthetic pathway was then inferred based on the genes
identified and through experimental validation of individual hopanoid molecules.
The genome data of R. udaipurense JA643(T) will be useful in understanding the
functional features of hopanoids in this bacterium.
PMID- 25117431
TI - Anthropometric and physiological profiling of youth soccer goalkeepers.
AB - Studies focused on position-related characteristics of young soccer players often
ignore the goalkeepers. The aim of this study was to examine the effect of
playing position on anthropometry, physiological attributes, soccer skills, and
goal orientation across adolescence. One hundred forty-five soccer players age 11
19 y were assessed in training experience, body size, maturation, physiological
parameters, soccer skills, and goal orientation. Factorial ANOVA was used to test
the effect of age group, playing position, and respective interaction terms,
while analysis of variance was used to compare goalkeepers vs outfielders in
middle (under 13 [U-13] and U-15) and late (U-17 and U-19) adolescence.
Discriminant analysis was used to identify the variables that contributed to
explaining playing positions. Age group was a consistent source of variation for
all variables except task and ego orientations. Fat mass, agility, endurance,
dribbling speed, shooting accuracy, and passing were affected by the gradient
derived from the classification between goalkeepers and outfielders. It was
possible to correctly classify the playing position based on fat-free mass and 3
manipulative skills in younger players and on 4 skills in U-17 and U-19 soccer
players. Future research should include longitudinal information to improve our
understanding of the factors that contribute to distinguish goalkeepers from
outfielders.
PMID- 25117433
TI - Effects of Sprint Training With or Without Ball Carry in Elite Rugby Players.
AB - PURPOSE: To compare the effects of sprint training with or without ball carry on
the sprint performance of elite rugby league players. METHODS: Twenty-four elite
rugby league players were divided into a ball-carry group (BC; n = 12) and a no
ball-carry group (NBC; n = 12). The players of the BC group were required to
catch and carry the ball under 1 arm during each sprint, whereas the NBC group
performed sprints without carrying a ball. The 8-wk training intervention took
place during the precompetitive phase of the season and consisted of 2
sessions/wk. Sprint performance was measured before and after the training
intervention with 40-m linear sprints performed under 2 conditions: with and
without ball carry. Split times of 10, 20, and 40 m were recorded for further
analysis. A 3-way (group * time * condition) factorial ANOVA was performed to
compare changes in sprint performance with and without the ball, before and after
the training intervention for both BC and NBC training groups Results: The BC and
NBC groups experienced similar improvements in 10-, 20-, and 40-m sprint times
and accelerations, regardless of the condition under which the sprint tests were
performed (P = .19). CONCLUSIONS: Sprint training while carrying a rugby ball is
as effective as sprint training without carrying a rugby ball for improving the
sprint performance of elite rugby league players.
PMID- 25117432
TI - Molecular signaling network motifs provide a mechanistic basis for cellular
threshold responses.
AB - BACKGROUND: Increasingly, there is a move toward using in vitro toxicity testing
to assess human health risk due to chemical exposure. As with in vivo toxicity
testing, an important question for in vitro results is whether there are
thresholds for adverse cellular responses. Empirical evaluations may show
consistency with thresholds, but the main evidence has to come from mechanistic
considerations. OBJECTIVES: Cellular response behaviors depend on the molecular
pathway and circuitry in the cell and the manner in which chemicals perturb these
circuits. Understanding circuit structures that are inherently capable of
resisting small perturbations and producing threshold responses is an important
step towards mechanistically interpreting in vitro testing data. METHODS: Here we
have examined dose-response characteristics for several biochemical network
motifs. These network motifs are basic building blocks of molecular circuits
underpinning a variety of cellular functions, including adaptation, homeostasis,
proliferation, differentiation, and apoptosis. For each motif, we present
biological examples and models to illustrate how thresholds arise from specific
network structures. DISCUSSION AND CONCLUSION: Integral feedback, feedforward,
and transcritical bifurcation motifs can generate thresholds. Other motifs (e.g.,
proportional feedback and ultrasensitivity)produce responses where the slope in
the low-dose region is small and stays close to the baseline. Feedforward control
may lead to nonmonotonic or hormetic responses. We conclude that network motifs
provide a basis for understanding thresholds for cellular responses.
Computational pathway modeling of these motifs and their combinations occurring
in molecular signaling networks will be a key element in new risk assessment
approaches based on in vitro cellular assays.
PMID- 25117435
TI - Time-resolved infrared spectroscopic studies of ligand dynamics in the active
site from cytochrome c oxidase.
AB - The catalytic site of heme-copper oxidases encompasses two close-lying ligand
binding sites: the heme, where oxygen is bound and reduced and the CuB atom,
which acts as ligand entry and release port. Diatomic gaseous ligands with a
dipole moment, such as the signaling molecules carbon monoxide (CO) and nitric
oxide (NO), carry clear infrared spectroscopic signatures in the different states
that allow characterization of the dynamics of ligand transfer within, into and
out of the active site using time-resolved infrared spectroscopy. We review the
nature and diversity of these processes that have in particular been
characterized with CO as ligand and which take place on time scales ranging from
femtoseconds to milliseconds. These studies have advanced our understanding of
the functional ligand pathways and reactivity in enzymes and more globally
represent intriguing model systems for mechanisms of ligand motion in a confined
protein environment. This article is part of a Special Issue entitled:
Vibrational spectroscopies and bioenergetic systems.
PMID- 25117436
TI - Reliability and validity of a new variable-power performance test in road
cyclists.
AB - CONTEXT: Road cycle racing is characterized by significant variability in
exercise intensity. Existing protocols attempting to model this aspect display
inadequate variation in power output. Furthermore, the reliability of protocols
representative of road cycle racing is not well known. There are also minimal
data regarding the physiological parameters that best predict performance during
variable-power cycling. PURPOSE: To determine the reliability of mean power
output during a new test of variable-power cycling and establish the relationship
between physiological attributes typically measured during an incremental
exercise test and performance during the variable-power cycling test (VCT).
METHODS: Fifteen trained male cyclists (mean +/- SD age 33 +/- 6.5 y, VO2max 57.9
+/- 4.8 mL . kg-1 . min-1) performed an incremental exercise test to exhaustion
for determination of physiological attributes, 2 VCTs (plus familiarization), and
a 30-km time trial. The VCT was modeled on data from elite men's road racing and
included significant variation in power output. RESULTS: Mean power output during
the VCT showed good reliability (r = .92, CV% = 1.98). Relative power during the
self-paced sections of the VCT was most correlated with maximal aerobic power (r
= .79) and power at the second ventilatory threshold (r = .69). Blood lactate
concentration showed poor reliability between trials (CV% = 13.93%). CONCLUSIONS:
This study has demonstrated a new reliable protocol simulating the stochastic
nature of road cycling races. Further research is needed to determine which
factors predict performance during variable-power cycling and the validity of the
test in monitoring longitudinal changes in cycling performance.
PMID- 25117434
TI - Protein as chemical cue: non-nutritional growth enhancement by exogenous protein
in Pseudomonas putida KT2440.
AB - Research pertaining to microbe-microbe and microbe-plant interactions has been
largely limited to small molecules like quorum sensing chemicals. However, a few
recent reports have indicated the role of complex molecules like proteins and
polysaccharides in microbial communication. Here we demonstrate that exogenous
proteins present in culture media can considerably accelerate the growth of
Pseudomonas putida KT2440, even when such proteins are not internalized by the
cells. The growth enhancement is observed when the exogenous protein is not used
as a source of carbon or nitrogen. The data show non-specific nature of the
protein inducing growth; growth enhancement was observed irrespective of the
protein type. It is shown that growth enhancement is mediated via increased
siderophore secretion in response to the exogenous protein, leading to better
iron uptake. We highlight the ecological significance of the observation and
hypothesize that exogenous proteins serve as chemical cues in the case of
P.putida and are perceived as indicator of the presence of competitors in the
environment. It is argued that enhanced siderophore secretion in response to
exogenous protein helps P.putida establish numerical superiority over competitors
by way of enhanced iron assimilation and quicker utilization of aromatic
substrates.
PMID- 25117437
TI - Health Promotion International - maintaining our vision for the future.
PMID- 25117438
TI - A genetic screen in Drosophila for regulators of human prostate cancer
progression.
AB - To uncover the mechanism by which human prostate cancer progresses, we performed
a genetic screen for regulators of human prostate cancer progression using the
Drosophila accessory gland, a functional homolog of the mammalian prostate. Cell
growth and migration of secondary cells in the adult male accessory gland were
found to be regulated by paired, N-cadherin, and E-cadherin, which are Drosophila
homologues of regulators of human prostate cancer progression. Using this
screening system, we also identified three genes that promoted growth and
migration of secondary cells in the accessory gland. The human homologues of
these candidate genes - MRGBP, CNPY2, and MEP1A - were found to be expressed in
human prostate cancer model cells and to promote replication and invasiveness in
these cells. These findings suggest that the development of the Drosophila
accessory gland and human prostate cancer cell growth and invasion are partly
regulated through a common mechanism. The screening system using the Drosophila
accessory gland can be a useful tool for uncovering the mechanisms of human
prostate cancer progression.
PMID- 25117439
TI - Axl is a novel target of withaferin A in the induction of apoptosis and the
suppression of invasion.
AB - Withaferin A, a withanolide derived from the medicinal plant Withania somnifera,
has been reported to exhibit anti-tumorigenic activity against various cancer
cells. In this study, we show that withaferin A inhibits the constitutive and
recombinant human growth-arrest-specific protein 6 (rhGas6)-induced
phosphorylation of Axl and STAT3. In addition, withaferin A also induces the down
regulation of Axl protein expression in a lysosome-dependent manner and inhibits
rhGas6-induced wound healing and cell migration. Furthermore, the overexpression
of Axl attenuates withaferin A-induced apoptosis. Taken together, the data from
the present study indicate that the withaferin A-mediated down-regulation of the
Gas6/Axl signaling pathway mediates the inhibition of cell migration and the
induction of apoptosis.
PMID- 25117441
TI - Introducing transglycosylation activity in Bacillus licheniformis alpha-amylase
by replacement of His235 with Glu.
AB - To understand the role of His and Glu in the catalytic activity of Bacillus
licheniformis alpha-amylase (BLA), His235 was replaced with Glu. The mutant
enzyme, H235E, was characterized in terms of its mode of action using labeled and
unlabeled maltooctaose (Glc8). H235E predominantly produced maltotridecaose
(Glc13) from Glc8, exhibiting high substrate transglycosylation activity, with
Km=0.38mM and kcat/Km=20.58mM(-1)s(-1) for hydrolysis, and Km2=18.38mM and
kcat2/Km2=2.57mM(-1)s(-1) for transglycosylation, while the wild-type BLA
exhibited high hydrolysis activity exclusively. Glu235-located on a wide open
groove near subsite +1-is likely involved in transglycosylation via formation of
an alpha-1,4-glycosidic linkage and may recognize and stabilize the non-reducing
end glucose of the acceptor molecule.
PMID- 25117440
TI - Ambra1 modulates starvation-induced autophagy through AMPK signaling pathway in
cardiomyocytes.
AB - Recent research has revealed a role for Ambra1, an autophagy-related gene-related
(ATG) protein, in the autophagic pro-survival response, and Ambra1 has been shown
to regulate Beclin1 and Beclin1-dependent autophagy in embryonic stem cells and
cancer cells. However, whether Ambra1 plays an important role in the autophagy
pathway in cardiomyocytes is unknown. In this study, we hypothesized that Ambra1
is an important regulator of autophagy and apoptosis in cardiomyocytes. To test
this hypothesis, we confirmed autophagic activity in serum-starved cardiomyocytes
by assessing endogenous microtubule-associated protein 1 light chain 3 (LC3)
localization, the presence of autophagosomes and LC3 protein levels. Cell
apoptosis and viability were measured by annexin-V and PI staining and MTT
assays. We determined that serum deprivation-induced autophagy was associated
with Ambra1 upregulation in cardiomyocytes. When Ambra1 expression was reduced by
siRNA, the cardiomyocytes were more sensitive to staurosporine-induced apoptosis.
In addition, co-immunoprecipitation of Ambra1 and Beclin1 demonstrated that
Ambra1 and Beclin1 interact in serum-starved or rapamycin-treated cardiomyocytes,
suggesting that Ambra1 regulates autophagy in cardiomyocytes by interacting with
Beclin1. Finally, we determined that starvation stress-induced activation of
Ambra1 contributes to the attenuation of adaptive AMP-activated protein kinase
(AMPK) signaling. In conclusion, Ambra1 is a crucial regulator of autophagy and
apoptosis through AMPK signaling pathway in cardiomyocytes that maintains the
balance between autophagy and apoptosis.
PMID- 25117442
TI - Dynamic regulation of the microtubule and actin cytoskeleton in zebrafish
epiboly.
AB - Gastrulation is a key developmental stage with striking changes in morphology.
Coordinated cell movements occur to bring cells to their correct positions in a
timely manner. Cell movements and morphological changes are accomplished by
precisely controlling dynamic changes in cytoskeletal proteins, microtubules, and
actin filaments. Among those cellular movements, epiboly produces the first
distinct morphological changes in teleosts. In this review, I describe epiboly
and its mechanics, and the dynamic changes in microtubule networks and actin
structures, mainly in zebrafish embryos. The factors regulating those
cytoskeletal changes will also be discussed.
PMID- 25117443
TI - Inhibition of N-acetylglucosaminyltransferase V enhances sensitivity of
radiotherapy in human prostate cancer.
AB - The purpose of this study was to investigate the relationship between N
acetylglucosaminyltransferase V (GnT-V) and radiation sensitivity of prostate
cancer (PCa) cells both in vitro and in vivo. Firstly, the GnT-V expression was
studied in 84 cases of PCa tissues, in which higher level of GnT-V was detected
more frequently in the advanced tumors. Secondly, the GnT-V stably suppressed
cell lines PCa/1079 (Lncap/1079 and PC3/1079) were constructed from PCa cell
lines (Lncap and PC3) in vitro. Attenuation of GnT-V inhibited cell
proliferation, migration and increased apoptosis, which resulted in enhanced
radiation sensitivity of PCa cells. The underlying mechanism may be relevant to
the increasing ratio of Bax/Bcl-2, the blocking transcription of NF-kappaB and
the reduction of cell cycle G2-M arrest. Finally, in in vivo study, compared with
control groups, the irradiated PCa xenograft nude mice of PCa/1079 indicated to
reduce tumor-growth rate and enhance survival time. Summary, our studies showed
that inhibition of GnT-V probably improved PCa cells' radiation sensitivity.
PMID- 25117444
TI - Viral and chloroplastic signals essential for initiation and efficiency of
translation in Agrobacterium tumefaciens.
AB - The construction of high-level protein expression vectors using the CaMV 35S
promoter in concert with highly efficient translation initiation signals for
Agrobacterium tumefaciens is a relatively less explored field compared to that of
Escherichia coli. In the current study, we experimentally investigated the
capacity of the CaMV 35S promoter to direct GFP gene expression in A. tumefaciens
in the context of different viral and chloroplastic translation initiation
signals. GFP expression and concomitant translational efficiency was monitored by
confocal microscopy and Western blot analysis. Among all of the constructs, the
highest level of translation was observed for the construct containing the phage
T7 translation initiation region followed by the chloroplastic Rubisco Large
Subunit (rbcL) 58-nucleotide 5' leader region including its SD-like sequence
(GGGAGGG). Replacing the SD-like (GGGAGGG) with non SD-like (TTTATTT) or
replacing the remaining 52 nucleotides of rbcL with nonspecific sequence
completely abolished translation. In addition, this 58 nucleotide region of rbcL
serves as a translational enhancer in plants when located within the 5' UTR of
mRNA corresponding to GFP. Other constructs, including those containing sequences
upstream of the coat proteins of Alfalfa Mosaic Virus, or the GAGG sequence of T4
phage or the chloroplastic atpI and/or PsbA 5' UTR sequence, supported low levels
of GFP expression or none at all. From these studies, we propose that we have
created high expression vectors in A. tumefaciens and/or plants which contain the
CaMV 35S promoter, followed by the translationally strong T7 SD plus RBS
translation initiation region or the rbcL 58-nucleotide 5' leader region upstream
of the gene of interest.
PMID- 25117445
TI - Nitrosylation of c heme in cd(1)-nitrite reductase is enhanced during catalysis.
AB - The reduction of nitrite into nitric oxide (NO) in denitrifying bacteria is
catalyzed by nitrite reductase. In several species, this enzyme is a heme
containing protein with one c heme and one d1 heme per monomer (cd1NiR), encoded
by the nirS gene. For many years, the evidence of a link between NO and this
hemeprotein represented a paradox, given that NO was known to tightly bind and,
possibly, inhibit hemeproteins, including cd1NiRs. It is now established that,
during catalysis, cd1NiRs diverge from "canonical" hemeproteins, since the
product NO rapidly dissociates from the ferrous d1 heme, which, in turn, displays
a peculiar "low" affinity for NO (KD=0.11 MUM at pH 7.0). It has been also
previously shown that the c heme reacts with NO at acidic pH but c heme
nitrosylation was not extensively investigated, given that in cd1NiR it was
considered a side reaction, rather than a genuine process controlling catalysis.
The spectroscopic study of the reaction of cd1NiR and its semi-apo derivative
(containing the sole c heme) with NO reported here shows that c heme
nitrosylation is enhanced during catalysis; this evidence has been discussed in
order to assess the potential of c heme nitrosylation as a regulatory process, as
observed for cytochrome c nitrosylation in mammalian mitochondria.
PMID- 25117446
TI - Arsenic trioxide inhibits cell proliferation and human papillomavirus oncogene
expression in cervical cancer cells.
AB - Arsenic trioxide (As2O3) has shown therapeutic effects in some leukemias and
solid cancers. However, the molecular mechanisms of its anticancer efficacy have
not been clearly elucidated, particularly in solid cancers. Our previous data
showed that As2O3 induced apoptosis of human papillomavirus (HPV) 16 DNA
immortalized human cervical epithelial cells and cervical cancer cells and
inhibited the expression of HPV oncogenes in these cells. In the present study,
we systemically examined the effects of As2O3 on five human cervical cancer cell
lines and explored the possible molecular mechanisms. MTT assay showed that HPV
negative C33A cells were more sensitive to growth inhibition induced by As2O3
than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells
were more sensitive to As2O3 than HPV 16-positive CaSki and SiHa cells. After
As2O3 treatment, both mRNA and protein levels of HPV E6 and E7 obviously
decreased in all HPV positive cell lines. In contrast, p53 and Rb protein levels
increased in all tested cell lines. Transcription factor AP-1 protein expression
decreased significantly in HeLa, CaSki and C33A cells with ELISA method. These
results suggest that As2O3 is a potential anticancer drug for cervical cancer.
PMID- 25117448
TI - Analyses on the mechanisms that underlie the chondroprotective properties of
calcitonin.
AB - INTRODUCTION: Calcitonin (CT) has recently been shown to display
chondroprotective effects. Here, we investigate the putative mechanisms by which
CT delivers these actions. METHODS: Immortalized C-28/I2 cells or primary adult
human articular chondrocytes (AHAC) were cultured in high-density micromasses to
investigate: (i) CT anabolic effects using qPCR and immuhistochemistry analysis;
(ii) CT anti-apoptotic effects using quantitation of Bax/Bcl gene products ratio,
TUNEL assay and caspase-3 expression; (iii) CT effects on CREB, COL2A1 and NFAT
transcription factors. RESULTS: CT (10(-10)-10(-8)nM) induced significant up
regulation of cartilage phenotypic markers (SOX9, COL2A1 and ACAN), with down
regulation of catabolic (MMP1 and MMP13 and ADAMTS5) gene products both in
resting and inflammatory conditions. This was mirrored by an augmented production
of type II collagen and accumulation of glycosaminoglycan- and proteoglycan-rich
extracellular matrix in vitro. Mechanistic analyses revealed only partial
involvement of cyclic AMP formation in these effects of CT. Congruently, using
reporter assays for specific transcription factors, there was no indication for
CREB activation, whereas the COL2A1 promoter was genuinely and directly activated
by cell exposure to CT. Phenotypically, these mechanisms supported the ability of
CT, whilst inactive on its own, to counteract the pro-apoptotic effects of IL
1beta, demonstrated by TUNEL-positive staining of chondrocytes and ratio of
BAX/BCL genes products. CONCLUSION: These data may provide a novel lead for the
development of CT-based chondroprotective strategies that rely on the engagement
of mechanisms that lead to augmented chondrocyte anabolism and inhibited
chondrocyte apoptosis.
PMID- 25117447
TI - Laboratory test surveillance following acute kidney injury.
AB - BACKGROUND: Patients with hospitalized acute kidney injury (AKI) are at increased
risk for accelerated loss of kidney function, morbidity, and mortality. We sought
to inform efforts at improving post-AKI outcomes by describing the receipt of
renal-specific laboratory test surveillance among a large high-risk cohort.
METHODS: We acquired clinical data from the Electronic health record (EHR) of 5
Veterans Affairs (VA) hospitals to identify patients hospitalized with AKI from
January 1st, 2002 to December 31st, 2009, and followed these patients for 1 year
or until death, enrollment in palliative care, or improvement in renal function
to estimated GFR (eGFR) >= 60 L/min/1.73 m(2). Using demographic data,
administrative codes, and laboratory test data, we evaluated the receipt and
timing of outpatient testing for serum concentrations of creatinine and any as
well as quantitative proteinuria recommended for CKD risk stratification.
Additionally, we reported the rate of phosphorus and parathyroid hormone (PTH)
monitoring recommended for chronic kidney disease (CKD) patients. RESULTS: A
total of 10,955 patients admitted with AKI were discharged with an eGFR<60
mL/min/1.73 m2. During outpatient follow-up at 90 and 365 days, respectively,
creatinine was measured on 69% and 85% of patients, quantitative proteinuria was
measured on 6% and 12% of patients, PTH or phosphorus was measured on 10% and 15%
of patients. CONCLUSIONS: Measurement of creatinine was common among all patients
following AKI. However, patients with AKI were infrequently monitored with
assessments of quantitative proteinuria or mineral metabolism disorder, even for
patients with baseline kidney disease.
PMID- 25117449
TI - The prognostic value of serum pregnancy-associated plasma protein A, S100 and
high sensitivity C-reactive protein in acute ischemic stroke patients without
heparin administration.
AB - OBJECTIVES: The concerns regarding the pre-analytical bias caused by medicine
treatments have been raised in the diagnosis and prognosis of ischemic stroke
recently. The aim of this study was to examine the prognostic value of serum
pregnancy-associated plasma protein A (PAPP-A), S100 and high sensitivity C
reactive protein (hs-CRP) in heparin-naive patients of acute ischemic stroke.
DESIGN AND METHODS: Serum levels of PAPP-A, S100 and hs-CRP were determined in
205 heparin-naive patients of acute ischemic stroke and 50 healthy controls.
Clinical information and radiological information were collected. Unfavorable
outcomes (stroke recurrence, myocardial infarction or death) were also recorded
after six months. The associations between serum biomarker levels and stroke
severity/outcome were assessed. RESULTS: Serum PAPP-A, S100 and hs-CRP levels
increased in patients compared with controls (P<0.05). S100 and hs-CRP levels
were significantly higher in patients with larger cerebral infarction sizes
(P<0.05) and more severe neurological impairment (P<0.05). Serum PAPP-A level
showed a progressive increase with the increase of stroke severity (P<0.05).
Serum hs-CRP and National Institutes of Health Stroke Scale (NIHSS) scores were
identified as independent predictors for unfavorable outcomes with odds ratios of
2.884 (1.154 to 7.210, P=0.023) and 2.887 (1.146 to 7.273, P=0.024),
respectively. CONCLUSION: Serum PAPP-A, S100 and hs-CRP were associated with
stroke severity or outcome after ischemic stroke and may offer complementary
information, essential for clinical decision making. Serum PAPP-A showed a
potential value for the evaluation of stroke clinically.
PMID- 25117451
TI - Amniotic membrane modulates innate immune response inhibiting PRRs expression and
NF-kappaB nuclear translocation on limbal myofibroblasts.
AB - Corneal damage observed in a viral infection such as herpetic stromal keratitis
is mainly caused by proinflammatory molecules released by resident cells in the
response to viral antigens. There are pattern recognition receptors like MDA5,
RIG-1, and TLR3, that recognize viral dsRNA and after activation, the innate
immune response is exacerbated inducing the synthesis and secretion of
inflammatory cytokines through NF-kappaB activation. Amniotic membrane (AM) has
demonstrated to reduce inflammation by several mechanisms, however the effect of
AM on innate immune receptors such as MDA5, RIG-1, and TLR3 has not been
reported. In this study, we have determined that the presence of AM significantly
inhibited the synthesis and secretion of proinflammatory cytokines on human
limbal myofibroblasts (HLM) stimulated with poly I:C. Similarly, the presence of
AM reduced the protein expression of MDA5, RIG-1, and TLR3 on poly I:C stimulated
HLM. Additionally, the presence of the AM significantly inhibited the NF-kappaB
nuclear translocation when the HLM were poly I:C stimulated, and concomitantly,
the AM was able to relocate cadherins affecting the myofibroblastic cellular
morphology. These results suggest that AM generates an anti-inflammatory
microenvironment, and specific inhibition of NFkappaB nuclear translocation on
infected corneal tissue would reduce the inflammation undesirable effects,
explaining in part the beneficial usefulness of transplanting AM on herpetic
stromal keratitis.
PMID- 25117450
TI - Autism-specific covariation in perceptual performances: "g" or "p" factor?
AB - BACKGROUND: Autistic perception is characterized by atypical and sometimes
exceptional performance in several low- (e.g., discrimination) and mid-level
(e.g., pattern matching) tasks in both visual and auditory domains. A factor that
specifically affects perceptive abilities in autistic individuals should manifest
as an autism-specific association between perceptual tasks. The first purpose of
this study was to explore how perceptual performances are associated within or
across processing levels and/or modalities. The second purpose was to determine
if general intelligence, the major factor that accounts for covariation in task
performances in non-autistic individuals, equally controls perceptual abilities
in autistic individuals. METHODS: We asked 46 autistic individuals and 46
typically developing controls to perform four tasks measuring low- or mid-level
visual or auditory processing. Intelligence was measured with the Wechsler's
Intelligence Scale (FSIQ) and Raven Progressive Matrices (RPM). We conducted
linear regression models to compare task performances between groups and patterns
of covariation between tasks. The addition of either Wechsler's FSIQ or RPM in
the regression models controlled for the effects of intelligence. RESULTS: In
typically developing individuals, most perceptual tasks were associated with
intelligence measured either by RPM or Wechsler FSIQ. The residual covariation
between unimodal tasks, i.e. covariation not explained by intelligence, could be
explained by a modality-specific factor. In the autistic group, residual
covariation revealed the presence of a plurimodal factor specific to autism.
CONCLUSIONS: Autistic individuals show exceptional performance in some perceptual
tasks. Here, we demonstrate the existence of specific, plurimodal covariation
that does not dependent on general intelligence (or "g" factor). Instead, this
residual covariation is accounted for by a common perceptual process (or "p"
factor), which may drive perceptual abilities differently in autistic and non
autistic individuals.
PMID- 25117455
TI - Simultaneous visualization of graphene grain boundaries and wrinkles with
structural information by gold deposition.
AB - Although line defects such as grain boundaries (GBs) and wrinkles are unavoidable
in graphene, difficulties in identification preclude studying their impact on
electronic and mechanical properties. As previous methods focus on a single type
of line defect, simultaneous measurements of both GBs and wrinkles with detailed
structural information have not been reported. Here, we introduce effective
visualization of both line defects by controlled gold deposition. Upon depositing
gold on graphene, single lines and double lines of gold nanoparticles (NPs) are
formed along GBs and wrinkles, respectively. Moreover, it is possible to analyze
whether a GB is stitched or overlapped, whether a wrinkle is standing or folded,
and the width of the standing collapsed wrinkle. Theoretical calculations show
that the characteristic morphology of gold NPs is due to distinct binding
energies of line defects, which are correlated to disrupting diffusion of NPs.
Our approach could be further exploited to investigate the defect structures of
other two-dimensional materials.
PMID- 25117452
TI - Chinese bone turnover marker study: reference ranges for C-terminal telopeptide
of type I collagen and procollagen I N-terminal peptide by age and gender.
AB - BACKGROUND: Bone formation marker procollagen I N-terminal peptide (PINP) and
resorption marker C-terminal telopeptide of type I collagen (beta-CTX) are useful
biomarkers for differential diagnosis and therapeutic evaluation of osteoporosis,
but reference values are required. METHODS: The multi-center, cross-sectional
Chinese Bone Turnover Marker Study included 3800 healthy volunteers in 5 Chinese
cities. Serum PINP, beta-CTX, parathyroid hormone (PTH) and 25OHD levels were
measured by chemiluminescence assay. Lumbar spine and proximal femur BMD were
measured by dual-energy X-ray absorptiometry. Serum PINP and beta-CTX levels were
assessed by age, gender, weight, recruitment latitude, levels of PTH and 25OHD.
RESULTS: Subjects (n = 1436, M:F, 500:936; mean age 50.6 +/- 19.6 years)
exhibited non-normally distributed PINP and beta-CTX peaking between 15-19 years,
gradually declining throughout adulthood, elevating within 10 years of
postmenopause, and then declining by age 70. In women between the age of 30 and
menopause, median PINP and beta-CTX levels were 40.42 (95% CI: 17.10-102.15) and
0.26 (95% CI: 0.08-0.72) ng/mL, respectively. beta-CTX and PINP were positively
linearly correlated (r = 0.599, P<0.001). beta-CTX correlated positively (r =
0.054 and 0.093) and PINP correlated negatively (r = -0.012 and -0.053) with
25OHD and PTH (P<0.05). CONCLUSIONS: We established Chinese reference ranges for
PINP and CTX. Chinese individuals exhibited high serum PINP and beta-CTX levels
between 15 and 19 years of age and at menopause, which gradually declined after
70 years of age.
PMID- 25117453
TI - Zinc finger MYND-type containing 8 promotes tumour angiogenesis via induction of
vascular endothelial growth factor-A expression.
AB - Zinc finger, MYND-type containing 8 (ZMYND8) encodes a receptor for activated C
kinase protein. Here, we report that ZMYND8 promotes angiogenesis in prostate
cancer xenografts in zebrafish, as well as tube formation in human umbilical
vascular endothelial cell (HUVEC) cultures. Using transcriptome analyses, we
found upregulation of ZMYND8 expression in both zebrafish prostate cancer
xenografts and prostate cancer samples from patients. In vitro and in vivo ZMYND8
knockdown suppressed angiogenesis, whereas ZMYND8 overexpression enhanced
angiogenesis. Notably, ZMYND8 induced vegfa mRNA expression selectively in
prostate cancer xenografts. Integrated analysis of human and zebrafish
transcriptomes, which identified ZMYND8, might be a powerful strategy to
determine also other molecular targets for inhibiting prostate cancer
progression.
PMID- 25117454
TI - Selenoprotein K form an intermolecular diselenide bond with unusually high redox
potential.
AB - Selenoprotein K (SelK) is a membrane protein involved in antioxidant defense,
calcium regulation and the ER-associated protein degradation pathway. We found
that SelK exhibits a peroxidase activity with a rate that is low but within the
range of other peroxidases. Notably, SelK reduced hydrophobic substrates, such as
phospholipid hydroperoxides, which damage membranes. Thus, SelK might be involved
in membrane repair or related pathways. SelK was also found to contain a
diselenide bond-the first intramolecular bond of that kind reported for a
selenoprotein. The redox potential of SelK was -257 mV, significantly higher than
that of diselenide bonds in small molecules or proteins. Consequently, SelK can
be reduced by thioredoxin reductase. These finding are essential for
understanding SelK activity and function.
PMID- 25117458
TI - Photocurrent spectroscopy of (n, m) sorted solution-processed single-walled
carbon nanotubes.
AB - Variable-wavelength photocurrent microscopy and photocurrent spectroscopy are
used to study the photoresponse of (n, m) sorted single-walled carbon nanotube
(SWNT) devices. The measurements of (n, m) pure SWCNT devices demonstrate the
ability to study the wavelength-dependent photoresponse in situ in a device
configuration and deliver photocurrent spectra that reflect the population of the
source material. Furthermore, we show that it is possible to map and determine
the chirality population within a working optoelectronic SWCNT device.
PMID- 25117457
TI - Chronic total occlusions in Sweden--a report from the Swedish Coronary
Angiography and Angioplasty Registry (SCAAR).
AB - INTRODUCTION: Evidence for the current guidelines for the treatment of patients
with chronic total occlusions (CTO) in coronary arteries is limited. In this
study we identified all CTO patients registered in the Swedish Coronary
Angiography and Angioplasty Registry (SCAAR) and studied the prevalence, patient
characteristics and treatment decisions for CTO in Sweden. METHODS AND RESULTS:
Between January 2005 and January 2012, 276,931 procedures (coronary angiography
or percutaneous coronary intervention) were performed in 215,836 patients
registered in SCAAR. We identified all patients who had 100% luminal diameter
stenosis known or assumed to be >= 3 months old. After exclusion of patients with
previous coronary artery bypass graft (CABG) surgery or coronary occlusions due
to acute coronary syndrome, we identified 16,818 CTO patients. A CTO was present
in 10.9% of all coronary angiographies and in 16.0% of patients with coronary
artery disease. The majority of CTO patients were treated conservatively and PCI
of CTO accounted for only 5.8% of all PCI procedures. CTO patients with diabetes
and multivessel disease were more likely to be referred to CABG. CONCLUSION: CTO
is a common finding in Swedish patients undergoing coronary angiography but the
number of CTO procedures in Sweden is low. Patients with CTO are a high-risk
subgroup of patients with coronary artery disease. SCAAR has the largest register
of CTO patients and therefore may be valuable for studies of clinical importance
of CTO and optimal treatment for CTO patients.
PMID- 25117456
TI - The effects of intraperitoneal clenbuterol injection on protein degradation and
myostatin expression differ between the sartorius and pectoral muscles of
neonatal chicks.
AB - The purpose of this study was to investigate the effects of injection of the
beta2-adrenergic receptor agonist clenbuterol on the skeletal muscles of neonatal
chicks (Gallus gallus domesticus). One-day-old chicks were randomly divided into
four groups and given a single intraperitoneal injection of clenbuterol (0.01,
0.1, or 1mg/kg) or phosphate-buffered saline. Twenty-four hours after the
injection, the sartorius muscles (which consist of both slow- and fast-twitch
fibers) of chicks that received 0.01 or 0.1mg/kg clenbuterol were significantly
heavier than those of controls, while there were no between-group differences in
the weight of the pectoral muscles, which consist of only fast-twitch fibers.
Muscle free N(t)-methylhistidine, regarded as an index of myofibrillar
proteolysis, was decreased in the sartorius muscle of the clenbuterol-injected
chicks, while it was not affected in the pectoral muscles. In the sartorius
muscle of the clenbuterol-injected chicks, myostatin and atrogin-1/MAFbx mRNA
expressions were decreased, while insulin-like growth factor-I was unaffected.
These observations suggested, in 1-day-old chicks, clenbuterol might increase
mass of the sartorius muscle by decreasing myostatin gene expression and protein
degradation.
PMID- 25117459
TI - The effects of lactation on impulsive behavior in vasopressin-deficient
Brattleboro rats.
AB - Vasopressin (AVP)-deficient Brattleboro rats develop a specific behavioral
profile, which-among other things-include altered cognitive performance. This
profile is markedly affected by alterations in neuroendocrine state of the animal
such as during lactation. Given the links between AVP and cognition we
hypothesized that AVP deficiency may lead to changes in impulsivity that is under
cognitive control and the changes might be altered by lactation. Comparing virgin
and lactating AVP-deficient female Brattleboro rats to their respective controls,
we assessed the putative lactation-dependent effects of AVP deficiency on
impulsivity in the delay discounting paradigm. Furthermore, to investigate the
basis of such effects, we assessed possible interactions of AVP deficiency with
GABAergic and serotonergic signaling and stress axis activity, systems playing
important roles in impulse control. Our results showed that impulsivity was
unaltered by AVP deficiency in virgin rats. In contrast a lactation-induced
increase in impulsivity was abolished by AVP deficiency in lactating females. We
also found that chlordiazepoxide-induced facilitation of GABAergic and imipramine
induced enhancement of serotonergic activity in virgins led to increased and
decreased impulsivity, respectively. In contrast, during lactation these effects
were visible only in AVP-deficient rats. These rats also exhibited increased
stress axis activity compared to virgin animals, an effect that was abolished by
AVP deficiency. Taken together, AVP appears to play a role in the regulation of
impulsivity exclusively during lactation: it has an impulsivity increasing effect
which is potentially mediated via stress axis-dependent mechanisms and fine
tuning of GABAergic and serotonergic function.
PMID- 25117460
TI - Clinical characteristics of pain in patients with pituitary adenomas.
AB - OBJECTIVE: Clinical presentation of pituitary adenomas frequently involves pain,
particularly headache, due to structural and functional properties of the tumour.
Our aim was to investigate the clinical characteristics of pain in a large cohort
of patients with pituitary disease. DESIGN: In a cross-sectional study, we
assessed 278 patients with pituitary disease (n=81 acromegaly; n=45 Cushing's
disease; n=92 prolactinoma; n=60 non-functioning pituitary adenoma). METHODS:
Pain was studied using validated questionnaires to screen for nociceptive vs
neuropathic pain components (painDETECT), determine pain severity, quality,
duration and location (German pain questionnaire) and to assess the impact of
pain on disability (migraine disability assessment, MIDAS) and quality of life
(QoL). RESULTS: We recorded a high prevalence of bodily pain (n=180, 65%) and
headache (n=178, 64%); adrenocorticotropic adenomas were most frequently
associated with pain (n=34, 76%). Headache was equally frequent in patients with
macro- and microadenomas (68 vs 60%; P=0.266). According to painDETECT, the
majority of the patients had a nociceptive pain component (n=193, 80%). Despite
high prevalence of headache, 72% reported little or no headache-related
disability (MIDAS). Modifiable factors including tumour size, genetic
predisposition, previous surgery, irradiation or medical therapy did not have
significant impact neither on neuropathic pain components (painDETECT) nor on
headache-related disability (MIDAS). Neuropathic pain and pain-related disability
correlated significantly with depression and impaired QoL. CONCLUSIONS: Pain
appears to be a frequent problem in pituitary disease. The data suggest that pain
should be integrated in the diagnostic and therapeutic work-up of patients with
pituitary disease in order to treat them appropriately and improve their QoL.
PMID- 25117462
TI - Prevalence of insulin resistance and risk of diabetes mellitus in HIV-infected
patients receiving current antiretroviral drugs.
AB - OBJECTIVE: HIV-infected patients had a higher prevalence of insulin resistance
(IR) and risk of diabetes mellitus (DM) than that observed in healthy controls,
but there are no data about the current prevalence considering the changes in HIV
presentation and the use of newer antiretroviral drugs. DESIGN: Longitudinal
study which involved 265 HIV patients without DM, receiving first (n=71) and
advanced lines of antiretroviral therapy (n=194). METHODS: Prevalence of IR
according to clinical and anthropometric variables, including dual X-ray
absorptiometry (DXA) scan evaluation. IR was defined as homeostasis model
assessment of IR>=3.8. Incident DM was assessed during the follow-up. RESULTS:
First-line patients had a short time of HIV infection, less hepatitis C virus
coinfection, and received mainly an efavirenz-based regimen. Overall, the
prevalence of IR was 21% (55 patients, 6% in first-line, 27% in pretreated). In a
logistic regression analysis, significant associations were found between the
waist/hip circumference ratio (RR 10; 95% CI 1.66-16; P<0.01, per unit), and
central fat in percentage (RR 1.08; 95% CI 1.01-1.17; P=0.04, per unit) as
evaluated by DXA, and IR. During 770.8 patient-years, DM was diagnosed in 8% (22
patients), mostly in pretreated patients (10 vs 4%; P=0.1). Thus, the overall
rate of incident DM was 2.85 per 100 person-years, mostly in previous IR (10.39
vs 0.82/100 person-years; P=0.01). CONCLUSIONS: A lower prevalence of IR is
observed in the current HIV-infected patients with fewer risk factors and
receiving newer antiretroviral drugs. IR continues to identify patients at high
risk for developing DM in the short term.
PMID- 25117461
TI - Alcohol and the risk for latent autoimmune diabetes in adults: results based on
Swedish ESTRID study.
AB - OBJECTIVE: Moderate alcohol consumption is associated with a reduced risk of type
2 diabetes. Our aim was to investigate whether alcohol consumption is associated
with the risk of latent autoimmune diabetes in adults (LADA), an autoimmune form
of diabetes with features of type 2 diabetes. DESIGN: A population-based case
control study was carried out to investigate the association of alcohol
consumption and the risk of LADA. METHODS: We used data from the ESTRID case
control study carried out between 2010 and 2013, including 250 incident cases of
LADA (glutamic acid decarboxylase antibodies (GADAs) positive) and 764 cases of
type 2 diabetes (GADA negative), and 1012 randomly selected controls aged >=35.
Logistic regression was used to estimate the odds ratios (ORs) of diabetes in
relation to alcohol intake, adjusted for age, sex, BMI, family history of
diabetes, smoking, and education. RESULTS: Alcohol consumption was inversely
associated with the risk of type 2 diabetes (OR 0.95, 95% CI 0.92-0.99 for every
5-g increment in daily intake). Similar results were observed for LADA, but
stratification by median GADA levels revealed that the results only pertained to
LADA with low GADA levels (OR 0.85, 95% CI 0.76-0.94/5 g alcohol per day),
whereas no association was observed with LADA having high GADA levels (OR 1.00,
95% CI 0.94-1.06/5 g per day). Every 5-g increment of daily alcohol intake was
associated with a 10% increase in GADA levels (P=0.0312), and a 10% reduction in
homeostasis model assessment of insulin resistance (P=0.0418). CONCLUSIONS: Our
findings indicate that alcohol intake may reduce the risk of type 2 diabetes and
type 2-like LADA, but has no beneficial effects on diabetes-related autoimmunity.
PMID- 25117463
TI - Hypogonadism as an additional indication for bariatric surgery in male morbid
obesity?
AB - OBJECTIVE: Male obesity is often associated with reduced levels of circulating
total (TT) and calculated free testosterone (cFT), with normal/reduced
gonadotropins. Bariatric surgery often improves sex steroid and sex hormone
binding globulin (SHBG) levels. The aim of this study was to assess the effects
of bariatric surgery on waist circumference (WC) and BMI, and on TT levels, in
morbidly obese men, stratified, according to the gonadal state, in eugonadal and
hypogonadal (TT<8 nmol/l) subjects. DESIGN: A cohort of morbidly obese patients
(29 with hypogonadism (HG) and 26 without) undergoing bariatric surgery (37, 10,
6, and 2, with Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding,
biliopancreatic diversion and gastric sleeve, respectively) was studied at 6 and
12 months from the operation. METHODS: Anthropometric parameters (weight, BMI,
WC) and sex hormones (gonadotropins, TT, cFT, estradiol (E2), SHBG) were
assessed. RESULTS: WC was the only parameter significantly correlated with
androgens, but not with E2, SHBG, and gonadotropins, at baseline. After surgery,
a significant increase in TT, cFT, and SHBG, accompanied by a decrease in E2, was
evident in the two groups. However, both TT and cFT, but not E2, SHBG, and
gonadotropin variations, were significantly higher in the hypogonadal group at
follow-up, with an overall 93% complete recovery from HG. Reduction in WC, but
not BMI, was significantly greater in hypogonadal men (DeltaWC=-29.4+/-21.6 vs
14.4+/-17.4 at 12 months, P=0.047). CONCLUSIONS: Recovery from obesity-associated
HG is one of the beneficial effects of bariatric surgery in morbidly obese men.
The present findings suggest that the gonadal state is a predictor of WC decrease
after bariatric surgery.
PMID- 25117464
TI - Cardiovascular risk in women with type 2 diabetes mellitus and prediabetes: is it
indeed higher than men?
AB - The relative risk for cardiovascular disease (CVD) events and mortality in
diabetic women (in comparison with non-diabetic women) is believed to be greater
than that in diabetic men. However, the absolute risk for CVD mortality and
morbidity does not appear to be higher in women. In general, there is
heterogeneity between studies, and whether there is any definite difference in
the CVD risk between sexes at any level of glycaemia is not known. The same
arguments also apply when comparing the CVD risk factors, such as lipid profiles
and systemic inflammation indices, which seem to be worse in women than in men
with diabetes mellitus (DM). The same questions emerge at any given glycaemic
state: are women at worse risk and do they have a worse risk factor profile than
men? These issues have yet to be resolved. Similar, though less extensive, data
have been reported for prediabetes. Furthermore, women with DM are suboptimally
treated compared with men regarding lipid and blood pressure targets. Large
prospective studies representative of the general population are therefore needed
to define the differences between sexes regarding CVD events and mortality at a
given glucose level and after adjusting for any other confounders.
PMID- 25117465
TI - GEPNETs update: Radionuclide therapy in neuroendocrine tumors.
AB - Peptide receptor radionuclide therapy (PRRT) is a promising new treatment
modality for inoperable or metastasized gastroenteropancreatic neuroendocrine
tumors (GEPNETs) patients. Most studies report objective response rates in 15-35%
of patients. Also, outcome in terms of progression free survival (PFS) and
overall survival compares very favorably with that for somatostatin analogs,
chemotherapy, or new, 'targeted' therapies. They also compare favorably to PFS
data for liver-directed therapies. Two decades after the introduction of PRRT,
there is a growing need for randomized controlled trials comparing PRRT to
'standard' treatment, that is treatment with agents that have proven benefit when
tested in randomized trials. Combining PRRT with liver-directed therapies or with
targeted therapies could improve treatment results. The question to be answered,
however, is whether a combination of therapies performed within a limited time
span from one another results in a better PFS than a strategy in which other
therapies are reserved until after (renewed) tumor progression. Randomized
clinical trials comparing PRRT with other treatment modalities should be
undertaken to determine the best treatment options and treatment sequelae for
patients with GEPNETs.
PMID- 25117466
TI - Ten weeks of aerobic training does not result in persistent changes in VLDL
triglyceride turnover or oxidation in healthy men.
AB - OBJECTIVE: Very low density lipoprotein triglyceride (VLDL-TG) and free fatty
acids (FFA) constitute a substantial proportion of human energy supply both at
rest and during exercise. Exercise acutely decreases VLDL-TG concentration, and
VLDL-TG clearance is increased after an exercise bout. However, the effects of
long-term training are not clear. DESIGN: The aim was to investigate long-term
effects of training by direct assessments of VLDL-TG and palmitate kinetics and
oxidation in healthy lean men (n=9) at rest, before and after a 10-week training
program, compared with a non-training control group (n=9). METHODS: VLDL-TG
kinetics were assessed by a primed constant infusion of [1-14C]VLDL-TG, and VLDL
TG oxidation by specific activity (14CO2) in expired air. The metabolic study
days were placed 60-72 h after the last exercise bout. RESULTS: Palmitate
kinetics and oxidation were assessed by a 2 h constant infusion of [9,10
(3)H]palmitate. In the training group (n=9), maximal oxygen uptake increased
significantly by ~20% (P<0.05), and the insulin sensitivity (assessed by the
hyperinsulinemic-euglycemic clamp) improved significantly (P<0.05). Despite these
metabolic improvements, no changes were observed in VLDL-TG secretion, clearance,
or oxidation or in palmitate kinetics. CONCLUSION: We conclude that 10 weeks of
exercise training did not induce changes in VLDL-TG and palmitate kinetics in
healthy lean men.
PMID- 25117467
TI - Nanocrystalline calcitic lens arrays fabricated by self-assembly followed by
amorphous-to-crystalline phase transformation.
AB - Natural calcium carbonate-based nanocomposites often have superior physical
properties and provide a comprehensive source for bioinspired synthetic
materials. Here we present thermodynamically stable, transparent CaCO3 microlens
arrays (MLA) produced by transforming an amorphous CaCO3 phase into
nanocrystalline calcite. We analyze the structure and properties of crystallized
MLA by X-ray scattering, transmitted and polarized light microscopy, and electron
microscopy and find that MLA are crystallized in spherulite-like patterns without
changing the shape of the microlens. The key finding is that nanocrystallinity of
the calcite formed diminishes structural anisotropy on the wavelength scale and
results in greatly reduced birefringent effects. The remnant preferred
orientation of the optical axes of calcite crystals in the plane of the microlens
arrays leads to some directionality of optical properties, which may be
beneficial for technical applications.
PMID- 25117468
TI - Cardiac fibrosis in end-stage human heart failure and the cardiac natriuretic
peptide guanylyl cyclase system: regulation and therapeutic implications.
AB - Left ventricular assist device (LVAD) support has been used in the treatment of
end-stage heart failure (HF), however use of anti-fibrotic co-therapies may
improve prognosis. Natriuretic peptides (NPs) possess anti-fibrotic properties
through their receptors, GC-A/GC-B/NPR-C. We sought to evaluate cardiac fibrosis
and the endogenous NP system in end-stage HF with and without LVAD therapy and to
assess the anti-fibrotic actions of the dual GC-A/-B activator CD-NP in vitro.
Collagen (Col) protein content was assessed by Picrosirius Red staining and NPs,
NP receptors, and Col I mRNA expression were determined by qPCR in LV tissue from
patients in end-stage HF (n=13), after LVAD support (n=5) and in normal subjects
(n=6). Col I mRNA and protein levels in cardiac fibroblasts (CFs) pretreated with
CD-NP were compared to those of BNP or CNP pretreatment. The LV in end-stage HF
was characterized by higher Col I mRNA expression and Col protein deposition
compared to normal which was sustained after LVAD support. ANP and BNP mRNA
expressions were higher while CNP was lower in end-stage HF LV. GC-A expression
did not change while GC-B and NPR-C increased compared to normal LV. The changes
in NP system expression were not reversed after LVAD support. In vitro, CD-NP
reduced Col I production stimulated by TGF-beta 1 greater than BNP or CNP in CFs.
We conclude that the failing LV is characterized by increased fibrosis and
reduced CNP gene expression. LVAD support did not reverse Col deposition nor
restore CNP production, suggesting a therapeutic opportunity for CD-NP.
PMID- 25117471
TI - Mercury telluride colloidal quantum dots: electronic structure, size-dependent
spectra, and photocurrent detection up to 12 MUm.
AB - HgTe colloidal quantum dots are synthesized with high monodispersivity with sizes
up to ~15 nm corresponding to a room temperature absorption edge at ~5 MUm. The
shape is tetrahedral for larger sizes and up to five peaks are seen in the
absorption spectra with a clear size dependence. The size range of the HgTe
quantum dots is extended to ~20 nm using regrowth. The corresponding room
temperature photoluminescence and absorption edge reach into the long-wave
infrared, past 8 MUm. Upon cooling to liquid nitrogen temperature, a
photoconductive response is obtained in the long-wave infrared region up to 12
MUm. Configuration-interaction tight-binding calculations successfully explain
the spectra and the size dependence. The five optical features can be assigned to
sets of single hole to single electron transitions whose strengths are strongly
influenced by the multiband/multiorbital character of the quantum-dot electronic
states.
PMID- 25117469
TI - TSLPR deficiency attenuates atherosclerotic lesion development associated with
the inhibition of TH17 cells and the promotion of regulator T cells in ApoE
deficient mice.
AB - AIMS: We generated thymic stromal lymphopoietin R-chain deficient apolipoprotein
E-double knockout (ApoE-TSLPR DKO) mice to directly explore the role of thymic
stromal lymphopoietin (TSLP) in atherogenesis. METHODS AND RESULTS: Both thymic
stromal lymphopoietin (TSLP) and its receptor are expressed in atherosclerotic
aortas of apolipoprotein E knockout (ApoE KO) mice. Serum thymic stromal
lymphopoietin (TSLP) is markedly increased in apolipoprotein E knockout (ApoE KO)
mice fed with a high fat diet (HFD). Arterial lesion formation was significantly
decreased in thymic stromal lymphopoietin R-chain deficient apolipoprotein E
double knockout (ApoE-TSLPR DKO) mice compared with apolipoprotein E knockout
(ApoE KO) mice. Bone marrow chimera studies indicated reduced lesions in
apolipoprotein E knockout (ApoE KO) mice which received the bone marrow of thymic
stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout (ApoE
TSLPR DKO) mice as well as in TSLPR KO mice which received bone marrow of ApoE
TSLPR DKO mice. Compared with apolipoprotein E knockout (ApoE KO) mice, IFN-gamma
secretion by activated T cells was increased but IL-4 expression was reduced in
thymic stromal lymphopoietin R-chain deficient apolipoprotein E-double knockout
(ApoE-TSLPR DKO) mice. Consisted with these results, the mRNA of IFN-gamma was
increased but IL-4 was reduced in root. These findings suggest that a reduction
in atherosclerotic lesions in thymic stromal lymphopoietin R-chain deficient
apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice may not be due to a
Th1/Th2 imbalance. On the other hand, the number of Th17 cells, the secretion of
IL-17A by activated CD4(+) T cells and the mRNA expression of IL-17A in root were
decreased in thymic stromal lymphopoietin R-chain deficient apolipoprotein E
double knockout (ApoE-TSLPR DKO) mice. Notably, the number of regulatory T cell
expression of IL-10 was increased in thymic stromal lymphopoietin R-chain
deficient apolipoprotein E-double knockout (ApoE-TSLPR DKO) mice. CONCLUSIONS:
Collectively, our data suggest that activating thymic stromal lymphopoietin
(TSLP) promotes atherosclerosis by inducing Th17/Treg imbalance through thymic
stromal lymphopoietin/thymic stromal lymphopoietin R-receptor (TSLP/TSLPR) signal
way in apolipoprotein E-deficient mice fed with HFD model.
PMID- 25117472
TI - A further note on the rises in sex ratio at birth during and just after the two
World Wars.
AB - It is well established that in most belligerent countries in World Wars 1 and 2,
sex ratios (proportions male at birth) rose during and just after hostilities:
then, a year or so later, they declined to normal levels. There is no established
explanation for these phenomena. I have previously written on this problem. Here,
I elaborate on my previous papers in three ways. First, further evidence (some
analytic and some synthetic) is adduced to support the hypothesis that the rises
were caused by high parental coital rates. Second, further evidence is adduced to
suggest that these high coital rates occurred disproportionately often in couples
of whom the man was (or had been) in the armed services. Thirdly, evidence is
offered to suggest why such rises in sex ratio were not reported in other
conflicts.
PMID- 25117470
TI - Proteomic analysis reveals a novel function of the kinase Sat4p in Saccharomyces
cerevisiae mitochondria.
AB - The Saccharomyces cerevisiae kinase Sat4p has been originally identified as a
protein involved in salt tolerance and stabilization of plasma membrane
transporters, implicating a cytoplasmic localization. Our study revealed an
additional mitochondrial (mt) localization, suggesting a dual function for Sat4p.
While no mt related phenotype was observed in the absence of Sat4p, its
overexpression resulted in significant changes of a specific mitochondrial
subproteome. As shown by a comparative two dimensional difference gel
electrophoresis (2D-DIGE) approach combined with mass spectrometry, particularly
two groups of proteins were affected: the iron-sulfur containing aconitase-type
proteins (Aco1p, Lys4p) and the lipoamide-containing subproteome (Lat1p, Kgd2p
and Gcv3p). The lipoylation sites of all three proteins could be assigned by
nanoLC-MS/MS to Lys75 (Lat1p), Lys114 (Kgd2p) and Lys102 (Gcv3p), respectively.
Sat4p overexpression resulted in accumulation of the delipoylated protein
variants and in reduced levels of aconitase-type proteins, accompanied by a
decrease in the activities of the respective enzyme complexes. We propose a
regulatory role of Sat4p in the late steps of the maturation of a specific subset
of mitochondrial iron-sulfur cluster proteins, including Aco1p and lipoate
synthase Lip5p. Impairment of the latter enzyme may account for the observed
lipoylation defects.
PMID- 25117474
TI - Accurate phylogenetic tree reconstruction from quartets: a heuristic approach.
AB - Supertree methods construct trees on a set of taxa (species) combining many
smaller trees on the overlapping subsets of the entire set of taxa. A 'quartet'
is an unrooted tree over 4 taxa, hence the quartet-based supertree methods
combine many 4-taxon unrooted trees into a single and coherent tree over the
complete set of taxa. Quartet-based phylogeny reconstruction methods have been
receiving considerable attentions in the recent years. An accurate and efficient
quartet-based method might be competitive with the current best phylogenetic tree
reconstruction methods (such as maximum likelihood or Bayesian MCMC analyses),
without being as computationally intensive. In this paper, we present a novel and
highly accurate quartet-based phylogenetic tree reconstruction method. We
performed an extensive experimental study to evaluate the accuracy and
scalability of our approach on both simulated and biological datasets.
PMID- 25117473
TI - The microvascular effects of insulin resistance and diabetes on cardiac
structure, function, and perfusion: a cardiovascular magnetic resonance study.
AB - AIMS: Type 2 diabetes mellitus is an independent risk factor for the development
of heart failure. To better understand the mechanism by which this occurs, we
investigated cardiac structure, function, and perfusion in patients with and
without diabetes. METHODS AND RESULTS: Sixty-five patients with no stenosis >30%
on invasive coronary angiography were categorized into diabetes (19) and non
diabetes (46) which was further categorized into prediabetes (30) and controls
(16) according to the American Diabetes Association guidelines. Each patient
underwent comprehensive cardiovascular magnetic resonance assessment. Left
ventricular (LV) mass, relative wall mass (RWM), Lagrangian circumferential
strain, LV torsion, and myocardial perfusion reserve (MPR) were calculated. LV
mass was higher in diabetics than non-diabetics (112.8 +/- 39.7 vs. 91.5 +/- 21.3
g, P = 0.01) and in diabetics than prediabetics (112.8 +/- 39.7 vs. 90.3 +/- 18.7
g, P = 0.02). LV torsion angle was higher in diabetics than non-diabetics (9.65
+/- 1.90 vs. 8.59 +/- 1.91 degrees , P = 0.047), and MPR was lower in diabetics
than non-diabetics (2.10 +/- 0.76 vs. 2.84 +/- 1.25 mL/g/min, P = 0.01). There
was significant correlation between MPR and early diastolic strain rate (r =
0.310, P = 0.01) and LV torsion (r = -0.306, P = 0.01). In multivariable linear
regression analysis, non-diabetics waist-hip ratio, but not body mass index, had
a significant association with RWM (Beta = 0.34, P = 0.02). CONCLUSION: Patients
with diabetes have increased LV mass, LV torsion, and decreased MPR. There is a
significant association between decreased MPR and increased LV torsion suggesting
a possible mechanistic link between microvascular disease and cardiac dysfunction
in diabetes.
PMID- 25117475
TI - Phase I dose-escalation study of cabazitaxel administered in combination with
cisplatin in patients with advanced solid tumors.
AB - INTRODUCTION: Cabazitaxel is a second-generation taxane with in vivo activity
against taxane-sensitive and -resistant tumor cell lines and tumor xenografts.
Cabazitaxel/cisplatin have therapeutic synergism in tumor-bearing mice, providing
a rationale for assessing this combination in patients with solid tumors.
METHODS: The primary objectives of this study were to determine dose-limiting
toxicities (DLTs) and the maximum tolerated dose (MTD) of a cabazitaxel/cisplatin
combined regimen (Part 1) and to assess antitumor activity at the MTD (Part 2).
Safety and pharmacokinetics (PK) were also examined. RESULTS: Twenty-five
patients with advanced solid tumors were enrolled (10 in Part 1; 15 in Part 2).
In Part 1, two dose levels were evaluated; the MTD for cabazitaxel/cisplatin
(given Q3W) was 15/75 mg/m(2). DLTs occurring during Cycle 1 at the maximum
administered dose (20/75 mg/m(2); acute renal failure and febrile neutropenia)
and the MTD (febrile neutropenia and hypersensitivity despite pre-medication)
were as expected for taxane/platinum combinations. For the 18 patients treated at
the MTD, the most frequent possibly related non-hematologic treatment-emergent
adverse events (Grade >= 3) were nausea (16.7%), fatigue, acute renal failure and
decreased appetite (each 11.1%). Neutropenia was the most frequent treatment
emergent Grade >= 3 hematologic laboratory abnormality at the MTD (77.8%). The
best overall response at the MTD was stable disease, observed in 66.7% of
patients. PK results of the combination did not appear to differ from single
agent administration for each agent. CONCLUSION: Combination treatment with
cabazitaxel/cisplatin had a manageable safety profile; no PK interactions were
evident. The recommended Phase II dose for this combination is
cabazitaxel/cisplatin 15/75 mg/m(2) administered every 3 weeks. Antitumor
activity findings suggest that further evaluation of this combination in disease
specific trials is warranted.
PMID- 25117476
TI - Identification of threshold prostate specific antigen levels to optimize the
detection of clinically significant prostate cancer by magnetic resonance
imaging/ultrasound fusion guided biopsy.
AB - PURPOSE: Prostate specific antigen sensitivity increases with lower threshold
values but with a corresponding decrease in specificity. Magnetic resonance
imaging/ultrasound targeted biopsy detects prostate cancer more efficiently and
of higher grade than standard 12-core transrectal ultrasound biopsy but the
optimal population for its use is not well defined. We evaluated the performance
of magnetic resonance imaging/ultrasound targeted biopsy vs 12-core biopsy across
a prostate specific antigen continuum. MATERIALS AND METHODS: We reviewed the
records of all patients enrolled in a prospective trial who underwent 12-core
transrectal ultrasound and magnetic resonance imaging/ultrasound targeted
biopsies from August 2007 through February 2014. Patients were stratified by each
of 4 prostate specific antigen cutoffs. The greatest Gleason score using either
biopsy method was compared in and across groups as well as across the population
prostate specific antigen range. Clinically significant prostate cancer was
defined as Gleason 7 (4 + 3) or greater. Univariate and multivariate analyses
were performed. RESULTS: A total of 1,003 targeted and 12-core transrectal
ultrasound biopsies were performed, of which 564 diagnosed prostate cancer for a
56.2% detection rate. Targeted biopsy led to significantly more upgrading to
clinically significant disease compared to 12-core biopsy. This trend increased
more with increasing prostate specific antigen, specifically in patients with
prostate specific antigen 4 to 10 and greater than 10 ng/ml. Prostate specific
antigen 5.2 ng/ml or greater captured 90% of upgrading by targeted biopsy,
corresponding to 64% of patients who underwent multiparametric magnetic resonance
imaging and subsequent fusion biopsy. Conversely a greater proportion of
clinically insignificant disease was detected by 12-core vs targeted biopsy
overall. These differences persisted when controlling for potential confounders
on multivariate analysis. CONCLUSIONS: Prostate cancer upgrading with targeted
biopsy increases with an increasing prostate specific antigen cutoff. Above a
prostate specific antigen threshold of 5.2 ng/ml most upgrading to clinically
significant disease was achieved by targeted biopsy. In our population this
corresponded to potentially sparing biopsy in 36% of patients who underwent
multiparametric magnetic resonance imaging. Below this value 12-core biopsy
detected more clinically insignificant cancer. Thus, the diagnostic usefulness of
targeted biopsy is optimized in patients with prostate specific antigen 5.2 ng/ml
or greater.
PMID- 25117477
TI - High conopeptide diversity in Conus tribblei revealed through analysis of venom
duct transcriptome using two high-throughput sequencing platforms.
AB - The venom of each species of Conus contains different kinds of pharmacologically
active peptides which are mostly unique to that species. Collectively, the ~500
700 species of Conus produce a large number of these peptides, perhaps exceeding
140,000 different types in total. To date, however, only a small fraction of this
diversity has been characterized via transcriptome sequencing. In addition, the
sampling of this chemical diversity has not been uniform across the different
lineages in the genus. In this study, we used high-throughput transcriptome
sequencing approach to further investigate the diversity of Conus venom peptides.
We chose a species, Conus tribblei, as a representative of a poorly studied clade
of Conus. Using the Roche 454 and Illumina platforms, we discovered 136 unique
and novel putative conopeptides belonging to 30 known gene superfamilies and 6
new conopeptide groups, the greatest diversity so far observed from a
transcriptome. Most of the identified peptides exhibited divergence from the
known conopeptides, and some contained cysteine frameworks observed for the first
time in cone snails. In addition, several enzymes involved in posttranslational
modification of conopeptides and also some proteins involved in efficient
delivery of the conopeptides to prey were identified as well. Interestingly, a
number of conopeptides highly similar to the conopeptides identified in a
phylogenetically distant species, the generalist feeder Conus californicus, were
observed. The high diversity of conopeptides and the presence of conopeptides
similar to those in C. californicus suggest that C. tribblei may have a broad
range of prey preferences.
PMID- 25117478
TI - Phylogenetic diversity and antibacterial activity of culturable fungi derived
from the zoanthid Palythoa haddoni in the South China Sea.
AB - Investigation on diversity of culturable fungi mainly focused on sponges and
corals, yet little attention had been paid to the fungal communities associated
with zoanthid corals. In this study, a total of 193 culturable fungal strains
were isolated from the zoanthid Palythoa haddoni collected in the South China
Sea, of which 49 independent isolates were identified using both morphological
characteristics and internal transcribed spacer (ITS) sequence analyses. Thirty
five strains were selected for phylogenetic analysis based on fungal ITS
sequences. The results indicated that 18 genera within eight taxonomic orders of
two phyla (seven orders of the phylum Ascomycota and one order of the phylum
Basidiomycota) together with one unidentified fungal strain have been achieved,
and Cladosporium sp. represented the dominant culturable genus. Particularly, 14
genera were isolated from a zoanthid for the first time. The antibacterial
activities of organic extracts of mycelia and fermentation broth of 49 identified
fungi were evaluated, and 29 (59.2 %) of the isolates displayed broad-spectrum or
selective antibacterial activity. More interestingly, more than 60 % of the
active fungal strains showed strong activity against two aquatic pathogenic
bacteria Nocardia brasiliensis and Vibrio parahaemolyticus, compared with other
pathogenic bacteria, indicating that zoanthid-derived fungi may protect its host
against pathogens. This is the first report of systematically phylogenetic
diversity and extensively antibacterial activity of zoanthid-derived fungi.
PMID- 25117481
TI - Intraoperative and anesthesia-related cardiac arrest and its mortality in older
patients: a 15-year survey in a tertiary teaching hospital.
AB - BACKGROUND: Little information is known about factors that influence
perioperative and anesthesia-related cardiac arrest (CA) in older patients. This
study evaluated the incidence, causes and outcome of intraoperative and
anesthesia-related CA in older patients in a Brazilian teaching hospital between
1996 and 2010. METHODS: During the study, older patients received 18,367
anesthetics. Data collected included patient characteristics, surgical
procedures, American Society of Anesthesiologists (ASA) physical status,
anesthesia type, medical specialty team and outcome. All CAs were categorized by
cause into one of four groups: patient's disease/condition-related, surgery
related, totally anesthesia-related or partially anesthesia-related. RESULTS: All
intraoperative CAs and deaths rates are shown per 10,000 anesthetics. There were
100 CAs (54.44; 95% confidence intervals [CI]: 44.68-64.20) and 68 deaths (37.02;
95% CI: 27.56-46.48). The majority of CAs were patient's disease-/condition
related (43.5; 95% CI: 13.44-73.68). There were six anesthesia-related CAs (3.26;
95% CI: 0.65-5.87) - 1 totally and 5 partially anesthesia-related, and three
deaths, all partially anesthesia-related (1.63; 95% CI: 0.0-3.47). ASA I-II
physical status patients presented no anesthesia-related CA. Anesthesia-related
CA, absent in the last five years of the study, was due to medication-/airway
related causes. ASA physical status was the most important predictor of CA (odds
ratio: 14.52; 95% CI: 4.48-47.08; P<0.001) followed by emergency surgery (odds
ratio: 8.07; 95% CI: 5.14-12.68; P<0.001). CONCLUSIONS: The study identified high
incidence of intraoperative CAs with high mortality in older patients. The large
majority of CAs were caused by factors not anesthesia-related. Anesthesia-related
CA and mortality rates were 3.26 and 1.63 per 10,000 anesthetics, with no
anesthesia-related CA in the last five years of the study. Major predictors of
intraoperative CAs were poorer ASA physical status and emergency surgery. All
anesthesia-related CAs were medication-related or airway-related, which is
important for prevention strategies.
PMID- 25117480
TI - Alteration of conserved alternative splicing in AMELX causes enamel defects.
AB - Tooth enamel is the most highly mineralized tissue in vertebrates. Enamel crystal
formation and elongation should be well controlled to achieve an exceptional
hardness and a compact microstructure. Enamel matrix calcification occurs with
several matrix proteins, such as amelogenin, enamelin, and ameloblastin. Among
them, amelogenin is the most abundant enamel matrix protein, and multiple
isoforms resulting from extensive but well-conserved alternative splicing and
postsecretional processing have been identified. In this report, we recruited a
family with a unique enamel defect and identified a silent mutation in exon 4 of
the AMELX gene. We show that the mutation caused the inclusion of exon 4, which
is almost always skipped, in the mRNA transcript. We further show, by generating
and characterizing a transgenic animal model, that the alteration of the ratio
and quantity of the developmentally conserved alternative splicing repertoire of
AMELX caused defects in enamel matrix mineralization.
PMID- 25117482
TI - A theoretical mathematical assessment of the effectiveness of coartemether in the
treatment of Plasmodium falciparum malaria infection.
AB - This study analysed the dynamics of blood stage malaria with immune response and
under administration of Coartem as a combination therapy. The techniques of
mathematical modelling were used in coming up and analysing the deterministic
model. Sensitivity analysis and statistical approaches were used to compare model
simulated treatment results with the use of Coartem and other antimalarial drugs.
We sought to theoretically assess if Coartem can bring improvement in the
treatment of malaria as compared to the other drugs. Our analysis and numerical
results suggest that Coartem compares well with other antimalarial drug that have
been on the market. However, the shortfall of our model is that it could not give
good comparative results between Coartem treatment and other combination
treatment schemes with similar mode of action. Our study predicted effects of
different drug treatment protocols in malaria using a theoretical mathematical
model, which gives an insight into potential effective treatment schemes.
PMID- 25117484
TI - Prevention of surgical site infection: still an important challenge in colorectal
surgery.
PMID- 25117485
TI - Occurrence of estrogens in water, sediment and biota and their ecological risk in
Northern Taihu Lake in China.
AB - Occurrence of five estrogens, including estrone (E1), 17beta-estradiol (E2),
estriol (E3), 17alpha-ethynylestradiol (EE2) and bisphenol A (BPA) in water,
sediment and biota in Northern Taihu Lake, were investigated and their ecological
risk was evaluated. Most of the target estrogens were widely distributed in the
eight studied sampling sites, and their levels showed a regional trend of Gong
Bay > Meiliang Bay > Zhushan Bay. The average concentrations of E1, E2, E3, EE2
and BPA ranged from 3.86 to 64.4 ng l(-1), 44.3 to 64.1 MUg kg(-1) dry weight and
58.6 to 115 MUg kg(-1) dry weight in water, sediments and biota, respectively. In
most cases, the average concentrations of BPA and E2 were higher than those of
other estrogens. E1, E3 and EE2 were found to be accumulated in river snails with
bioaccumulation factor values as high as 14,204, 35,327 and 20,127 l kg(-1),
respectively. E3 was also considered to be accumulated in clams. The evaluation
of environmental risk showed that the occurrence of E2 and EE2 in lakes might
pose a high risk to aquatic organisms. These findings provide important
information for estrogen control and management in the studied area.
PMID- 25117487
TI - Wavelet coherence analysis of prefrontal tissue oxyhaemoglobin signals as
measured using near-infrared spectroscopy in elderly subjects with cerebral
infarction.
AB - This study aims to assess the prefrontal functional connectivity using wavelet
coherence analysis of cerebral tissue oxyhaemoglobin concentration (Delta [HbO2])
signals in elderly subjects with cerebral infarction (CI) during the resting
state. Continuous recordings of near-infrared spectroscopy (NIRS) signals were
obtained from the left and right prefrontal lobes in 10 subjects with CI (age:
74.4+/-9.0years) and 18 healthy elderly subjects (age: 69.9+/-7.3years) during
the resting state. The coherence between left and right prefrontal Delta [HbO2]
oscillations in four frequency intervals (I, 0.6-2Hz; II, 0.145-0.6Hz; III, 0.052
0.145Hz and IV, 0.021-0.052Hz) was analyzed using wavelet coherence analysis. In
healthy elderly subjects, the Delta [HbO2] oscillations were significantly
wavelet coherent in intervals I and III (p<0.05), wavelet phase coherent in
intervals from I to IV. In elderly subjects with CI, the left and right Delta
[HbO2] oscillations were significantly wavelet coherent and phase coherent in
interval I (p<0.05). In elderly subjects with CI, the power and phase coherences
were significantly lower in interval III (p<0.01) than in healthy subjects. The
difference in wavelet coherence between the healthy elderly and elderly with CI
indicates an altered brain functional connectivity in CI patients. This may be
useful for assessing the effectiveness of functional recovery following a CI.
PMID- 25117486
TI - Residents health risk of Pb, Cd and Cu exposure to street dust based on different
particle sizes around zinc smelting plant, Northeast of China.
AB - The residents health risk of Pb, Cd and Cu exposure to street dust with different
particle sizes (<100 and <63 MUm) near Huludao Zinc Plant (HZP) was investigated
in this study. The average concentrations of Pb, Cd and Cu in the <100-MUm and
<63-MUm dust were 1,559, 178.5, 917.9 and 2,099, 198.4, 1,038 mg kg(-1),
respectively. It showed that smaller particles tended to contain higher element
concentrations. Metals in dust around HZP decreased gradually from the zinc
smelter to west and east directions. There was significantly positive correlation
among Pb, Cd and Cu in street dust with different particle sizes. The contents of
Pb, Cd and Cu in dust increased with decreasing pH or increasing organic matter.
Non-carcinogenic health risk assessment showed that the health index (HI) for
children and adult exposed to <63-MUm particles were higher than exposed to <100
MUm particles, which indicated that smaller particles tend to have higher non
carcinogenic health risk. Non-carcinogenic risk of Pb was the highest in both
particle sizes, followed by Cd and Cu. HI for Pb and Cd in both particle sizes
for children had exceeded the acceptable value, indicated that children living
around HZP were experiencing the non-carcinogenic health risk from Pb and Cd
exposure to street dust.
PMID- 25117488
TI - Podocyte proteins in congenital and minimal change nephrotic syndrome.
AB - BACKGROUND: Podocyte foot process effacement is a uniform finding in kidneys with
heavy proteinuria. Its molecular mechanisms, however, are unsolved. We analyzed
the expression of podocyte proteins in two kidney disorders: Congenital nephrotic
syndrome of the Finnish type (CNF) and minimal change nephrotic syndrome (MCNS).
METHODS: Immunoperoxidase and immunofluorescence stainings were used to
semiquantitatively analyze the expression of 13 and 4 podocyte proteins from
different cellular compartments in CNF and MCNS, respectively. RESULTS: The
expression of a major slit diaphragm (SD) protein, Neph 1, showed a 46-fold
decrease (p < 0.0001) in CNF kidneys as compared to controls. The three cytosolic
adaptor proteins, podocin, NCK1/2, CD2AP, connecting SD proteins to the actin
cytoskeleton were slightly upregulated (1.1-fold, 1.4-fold, and 3.3-fold,
respectively). Also, the staining of the two actin-regulator proteins, ACTN4 and
INF2, was modestly increased (2.2-fold and 1.7-fold, respectively, p < 0.0001).
Staining for alpha3-integrin showed 1.9-fold increase (p < 0.0001) indicating
that the major podocyte anchoring complex, alpha3beta1, was well preserved in CNF
glomeruli. In contrast to CNF kidneys, Neph1 FAT1, ACTN4, and CD2AP were quite
normally expressed in proteinuric and non-proteinuric MCNS kidneys. CONCLUSION:
CNF kidneys lacking nephrin show decreased expression of other SD proteins but
not cytosolic podocyte proteins involved in the foot process architecture or
function. In MCNS kidneys, these changes in expression were not observed.
PMID- 25117491
TI - Correlation of gross urine color with diagnostic findings in male cats with
naturally occurring urethral obstruction.
AB - Seventy-five male cats with urethral obstruction were prospectively enrolled to
evaluate gross urine color at urinary catheter placement for correlation with
diagnostic findings. Cats with darker red urine were more likely to be azotemic
(serum creatinine concentration >2.0 mg/dl [177 umol/l]), and urine color
correlated well with serum creatinine and serum potassium concentrations. Darker
urine color was negatively correlated with urine specific gravity. Urine color
was not associated with the presence or absence of lower urinary tract stones on
radiographs or ultrasound. Cats with darker red urine at the time of urinary
catheter placement are likely to have more significant metabolic derangements and
may require more aggressive supportive care.
PMID- 25117489
TI - A long non-coding RNA is required for targeting centromeric protein A to the
human centromere.
AB - The centromere is a specialized chromatin region marked by the histone H3 variant
CENP-A. Although active centromeric transcription has been documented for over a
decade, the role of centromeric transcription or transcripts has been elusive.
Here, we report that centromeric alpha-satellite transcription is dependent on
RNA Polymerase II and occurs at late mitosis into early G1, concurrent with the
timing of new CENP-A assembly. Inhibition of RNA Polymerase II-dependent
transcription abrogates the recruitment of CENP-A and its chaperone HJURP to
native human centromeres. Biochemical characterization of CENP-A associated RNAs
reveals a 1.3 kb molecule that originates from centromeres, which physically
interacts with the soluble pre-assembly HJURP/CENP-A complex in vivo, and whose
down-regulation leads to the loss of CENP-A and HJURP at centromeres. This study
describes a novel function for human centromeric long non-coding RNAs in the
recruitment of HJURP and CENP-A, implicating RNA-based chaperone targeting in
histone variant assembly.
PMID- 25117492
TI - Ionophore-based ion-selective optical nanosensors operating in exhaustive sensing
mode.
AB - Ion selective optical sensors are typically interrogated under conditions where
the sample concentration is not altered during measurement. We describe here an
alternative exhaustive detection mode for ion selective optical sensors. This
exhaustive sensor concept is demonstrated with ionophore-based nanooptodes either
selective for calcium or the polycationic heparin antidote protamine. In
agreement with a theoretical treatment presented here, linear calibration curves
were obtained in the exhaustive detection mode instead of the sigmoidal curves
for equilibrium-based sensors. The response range can be tuned by adjusting the
nanosensor loading. The nanosensors showed average diameters of below 100 nm and
the sensor response was found to be dramatically faster than that for film-based
optodes. Due to the strong binding affinity of the exhaustive nanosensors, total
calcium concentration in human blood plasma was successfully determined. Optical
determination of protamine in human blood plasma using the exhaustive nanosensors
was attempted, but was found to be less successful.
PMID- 25117493
TI - Genotoxic effects of water pollution on two fish species living in Karasu River,
Erzurum, Turkey.
AB - Karasu River, which is the only river in the Erzurum plain, is the source of the
Euphrates River (Eastern Anatolia of Turkey). The river is in a serious
environmental situation as a result of pollution by agricultural and industrial
sewage and domestic discharges. The present study aims to evaluate genotoxic
effects of toxic metals in chub, Leuciscus cephalus, and transcaucasian barb,
Capoeta capoeta, collected from contaminated site of the Karasu River, in
comparison with fish from an unpolluted reference site. Heavy metal
concentrations in surface water of the river were determined. The condition
factor (CF) was taken as a general biomarker of the health of the fish, and
genotoxicity assays such as micronucleus (MN) and other nuclear abnormalities
(NA) were carried out on the fish species studied. MN and NA such as kidney
shaped nucleus, notched nucleus, binucleated, lobed nucleus, and blebbed nucleus
were assessed in peripheral blood erythrocytes, gill epithelial cells, and liver
cells of the fish. A significant decrease in CF values associated with a
significant elevation in MN and NA frequencies was observed in fish collected
from the polluted sites compared with those from the reference site. Results of
the current study show the significance of integrating a set of biomarkers to
identify the effects of anthropogenic pollution. High concentrations of heavy
metals have a potential genotoxic effects, and the toxicity is possibly related
to industrial, agricultural, and domestic activities.
PMID- 25117494
TI - Geospatial assessment and monitoring of historical forest cover changes (1920
2012) in Nilgiri Biosphere Reserve, Western Ghats, India.
AB - Deforestation in the biosphere reserves, which are key Protected Areas has
negative impacts on biodiversity, climate, carbon fluxes and livelihoods.
Comprehensive study of deforestation in biosphere reserves is required to assess
the impact of the management effectiveness. This article assesses the changes in
forest cover in various zones and protected areas of Nilgiri Biosphere Reserve,
the first declared biosphere reserve in India which forms part of Western Ghats-a
global biodiversity hotspot. In this study, we have mapped the forests from
earliest available topographical maps and multi-temporal satellite data spanning
from 1920's to 2012 period. Mapping of spatial extent of forest cover, vegetation
types and land cover was carried out using visual interpretation technique. A
grid cell of 1 km * 1 km was generated for time series change analysis to
understand the patterns in spatial distribution of forest cover (1920-1973-1989
1999-2006-2012). The total forest area of biosphere reserve was found to be
5,806.5 km(2) (93.8 % of total geographical area) in 1920. Overall loss of forest
cover was estimated as 1,423.6 km(2) (24.5 % of the total forest) with reference
to 1920. Among the six Protected Areas, annual deforestation rate of >0.5 was
found in Wayanad wildlife sanctuary during 1920-1973. The deforestation in
Nilgiri Biosphere Reserve is mainly attributed to conversion of forests to
plantations and agriculture along with submergence due to construction of dams
during 1920 to 1989. Grid wise analysis indicates that 851 grids have undergone
large-scale negative changes of >75 ha of forest loss during 1920-1973 while,
only 15 grids have shown >75 ha loss during 1973-1989. Annual net rate of
deforestation for the period of 1920 to 1973 was calculated as 0.5 followed by
0.1 for 1973 to 1989. Our analysis shows that there was large-scale deforestation
before the declaration of area as biosphere reserve in 1986; however, the
deforestation has drastically reduced after the declaration due to high degree of
protection, thus indicating the secure future of reserve in the long term under
the current forest management practices. The present work will stand as the most
up-to-date assessment on the forest cover of the Nilgiri Biosphere Reserve with
immediate applications in monitoring and management of forest biodiversity.
PMID- 25117490
TI - DNA binding polarity, dimerization, and ATPase ring remodeling in the CMG
helicase of the eukaryotic replisome.
AB - The Cdc45/Mcm2-7/GINS (CMG) helicase separates DNA strands during replication in
eukaryotes. How the CMG is assembled and engages DNA substrates remains unclear.
Using electron microscopy, we have determined the structure of the CMG in the
presence of ATPgammaS and a DNA duplex bearing a 3' single-stranded tail. The
structure shows that the MCM subunits of the CMG bind preferentially to single
stranded DNA, establishes the polarity by which DNA enters into the Mcm2-7 pore,
and explains how Cdc45 helps prevent DNA from dissociating from the helicase. The
Mcm2-7 subcomplex forms a cracked-ring, right-handed spiral when DNA and
nucleotide are bound, revealing unexpected congruencies between the CMG and both
bacterial DnaB helicases and the AAA+ motor of the eukaryotic proteasome. The
existence of a subpopulation of dimeric CMGs establishes the subunit register of
Mcm2-7 double hexamers and together with the spiral form highlights how Mcm2-7
transitions through different conformational and assembly states as it matures
into a functional helicase.
PMID- 25117495
TI - Mercury speciation in plankton from the Cabo Frio Bay, SE--Brazil.
AB - Mercury (Hg) is considered a global pollutant, and the scientific community has
shown great concern about its toxicity as it may affect the biota of entire
systems, through bioaccumulation and bioamplification processes of its organic
form, methylmercury (MeHg), along food web. However, few research studies deal
with bioaccumulation of Hg from marine primary producers and the first-order
consumers. So, this study aims to determine Hg distribution and concentration
levels in phytoplankton and zooplankton in the Cabo Frio Bay, Brazil, a site
influenced by coastal upwelling. The results from Hg speciation analyses show
that inorganic mercury Hg(II) was the predominant specie in plankton from this
bay. The annual Hg species distribution in plankton shown mean concentration of
2.00 +/- 1.28 ng Hg(II) g(-1) and 0.15 +/- 0.08 ng MeHg g(-1) wet weight
(phytoplankton) and 2.5 +/- 2.03 ng Hg(II) g(-1) and 0.25 +/- 0.09 ng MeHg g(-1)
wet weight (zooplankton). Therefore, upwelling zones should be considered in the
Hg biogeochemical cycle models as a process that enhances Hg(II) bioaccumulation
in plankton, raising its bioavailability and shelf deposition.
PMID- 25117496
TI - Extensive transcription analysis of the Hyposoter didymator Ichnovirus genome in
permissive and non-permissive lepidopteran host species.
AB - Ichnoviruses are large dsDNA viruses that belong to the Polydnaviridae family.
They are specifically associated with endoparasitic wasps of the family
Ichneumonidae and essential for host parasitization by these wasps. We sequenced
the Hyposoter didymator Ichnovirus (HdIV) encapsidated genome for further
analysis of the transcription pattern of the entire set of HdIV genes following
the parasitization of four different lepidopteran host species. The HdIV genome
was found to consist of at least 50 circular dsDNA molecules, carrying 135 genes,
98 of which formed 18 gene families. The HdIV genome had general features typical
of Ichnovirus (IV) genomes and closely resembled that of the IV carried by
Hyposoter fugitivus. Subsequent transcriptomic analysis with Illumina technology
during the course of Spodoptera frugiperda parasitization led to the
identification of a small subset of less than 30 genes with high RPKM values in
permissive hosts, consisting with these genes encoding crucial virulence
proteins. Comparisons of HdIV expression profiles between host species revealed
differences in transcript levels for given HdIV genes between two permissive
hosts, S. frugiperda and Pseudoplusia includens. However, we found no evident
intrafamily gene-specific transcription pattern consistent with the presence of
multigenic families within IV genomes reflecting an ability of the wasps
concerned to exploit different host species. Interestingly, in two non-permissive
hosts, Mamestra brassiccae and Anticarsia gemmatalis (most of the parasitoid eggs
were eliminated by the host cellular immune response), HdIV genes were generally
less strongly transcribed than in permissive hosts. This suggests that successful
parasitism is dependent on the expression of given HdIV genes exceeding a
particular threshold value. These results raise questions about the mecanisms
involved in regulating IV gene expression according to the nature of the
lepidopteran host species encountered.
PMID- 25117499
TI - Advantages of crystallographic fragment screening: functional and mechanistic
insights from a powerful platform for efficient drug discovery.
AB - X-ray crystallography has been an under-appreciated screening tool for fragment
based drug discovery due to the perception of low throughput and technical
difficulty. Investigators in industry and academia have overcome these challenges
by taking advantage of key factors that contribute to a successful
crystallographic screening campaign. Efficient cocktail design and soaking
methodologies have evolved to maximize throughput while minimizing false
positives/negatives. In addition, technical improvements at synchrotron beamlines
have dramatically increased data collection rates thus enabling screening on a
timescale comparable to other techniques. The combination of available resources
and efficient experimental design has resulted in many successful
crystallographic screening campaigns. The three-dimensional crystal structure of
the bound fragment complexed to its target, a direct result of the screening
effort, enables structure-based drug design while revealing insights regarding
protein dynamics and function not readily obtained through other experimental
approaches. Furthermore, this "chemical interrogation" of the target protein
crystals can lead to the identification of useful reagents for improving
diffraction resolution or compound solubility.
PMID- 25117500
TI - Field-dependent anisotropic microrheological and microstructural properties of
dilute ferrofluids.
AB - We have measured microrheological and microstructural properties of a
superparamagnetic ferrofluid made of Mn0.75Zn0.25Fe2O4 (MZF) nanoparticles, using
passive microrheology in a home-built inverted microscope. Thermal motion of a
probe microsphere was measured for different values of an applied external
magnetic field and analysed. The analysis shows anisotropy in magneto-viscous
effect. Additional microrheological properties, such as storage modulus and loss
modulus and their transition are also seen. We have also obtained microstructural
properties such as elongational flow coefficient [Formula: see text] , relaxation
time constant [Formula: see text] , coefficient of dissipative magnetization
[Formula: see text] , etc., using the analysis given in Oliver Muller et al., J.
Phys.: Condens. Matter 18, S2623, (2006) and Stefan Mahle et al., Phys. Rev. E
77, 016305 (2008) over our measured viscosity data. Our values for the above
parameters are in agreement with earlier theoretical calculations and macro
rheological experimental measurements. These theoretical calculations consider an
ideal situation of zero-shear limit, which is best approximated only in the
passive microrheology technique described here and a first time measurement of
all these parameters with passive microrheology.
PMID- 25117501
TI - Elasticity and mechanical instability of charged lipid bilayers in ionic
solutions.
AB - We use coarse-grained Monte Carlo simulations to study the elastic properties of
charged membranes in solutions of monovalent and pentavalent counterions. The
simulation results of the two cases reveal trends opposite to each other. The
bending rigidity and projected area increase with the membrane charge density for
monovalent counterions, while they decrease for the pentavalent ions. These
observations can be related to the counterion screening of the lipid charges.
While the monovalent counterions only weakly screen the Coulomb interactions,
which implies a repulsive Coulomb system, the multivalent counterions condense on
the membrane and, through spatial charge correlations, make the effective
interactions due to the charged lipids attractive. The differences in the elastic
properties of the charged membranes in monovalent and multivalent counterion
solutions are reflected in the mechanisms leading to their mechanical instability
at high charge densities. In the former case, the membranes develop pores to
relieve the electrostatic tensile stresses, while in the latter case, the
membrane exhibits large wavelength bending instability.
PMID- 25117502
TI - Cancer genetic testing panels for inherited cancer susceptibility: the clinical
experience of a large adult genetics practice.
AB - Next-generation sequencing genetic testing panels for cancer susceptibility
(cancer panels) have recently become clinically available. At present, clinical
utility is unknown and there are no set criteria or guidelines established for
whom to offer such testing. Although it may be a cost-effective method to test
multiple cancer susceptibility genes concurrently, the rate of finding variants
of unknown significance (VUS) may be high and testing may yield mutations in
genes with no established management recommendations. We describe our Center's
experience over a 14-month period (April 2012-June 2013) for patient interest and
uptake in cancer panel testing and whether there were predictors of pursuing
testing or identifying mutations. Using a clinical ranking system, patients'
family histories were ranked from 0 to 3 (low likelihood to high likelihood for
underlying genetic susceptibility). The clinical ranking system was assessed to
determine its predictability of finding mutations. Of the 689 patients who met
inclusion criteria, the option of pursuing a cancer panel was discussed with 357
patients; 63 (17.6 %) patients pursued testing. Those who pursued testing were
more likely to be older, male, affected with cancer, affected with multiple
primary cancers, and had a higher clinical rank than non-pursuers. There were no
significant predictors of finding a mutation on panel testing. Of the 61 patients
who have received results, there was a 6.6 % mutation rate and 19.7 % VUS rate.
The yield of cancer panels in clinical practice is low and the strength of family
history alone may not predict likelihood of finding a mutation.
PMID- 25117498
TI - Interrogation of living myocardium in multiple static deformation states with
diffusion tensor and diffusion spectrum imaging.
AB - Diffusion tensor magnetic resonance imaging (MRI) reveals valuable insights into
tissue histo-anatomy and microstructure, and has steadily gained traction in the
cardiac community. Its wider use in small animal cardiac imaging in vivo has been
constrained by its extreme sensitivity to motion, exaggerated by the high heart
rates usually seen in rodents. Imaging of the isolated heart eliminates
respiratory motion and, if conducted on arrested hearts, cardiac pulsation. This
serves as an important intermediate step for basic and translational studies.
However, investigating the micro-structural basis of cardiac deformation in the
same heart requires observations in different deformation states. Here, we
illustrate the imaging of isolated rat hearts in three mechanical states
mimicking diastole (cardioplegic arrest), left-ventricular (LV) volume overload
(cardioplegic arrest plus LV balloon inflation), and peak systole (lithium
induced contracture). An optimised MRI-compatible Langendorff perfusion setup
with the radio-frequency (RF) coil integrated into the wet chamber was developed
for use in a 9.4T horizontal bore scanner. Signal-to-noise ratio improved
significantly, by 75% compared to a previous design with external RF coil, and
stability tests showed no significant changes in mean T1, T2 or LV wall thickness
over a 170 min period. In contracture, we observed a significant reduction in
mean fractional anisotropy from 0.32 +/- 0.02 to 0.28 +/- 0.02, as well as a
significant rightward shift in helix angles with a decrease in the proportion of
left-handed fibres, as referring to the locally prevailing cell orientation in
the heart, from 24.9% to 23.3%, and an increase in the proportion of right-handed
fibres from 25.5% to 28.4%. LV overload, in contrast, gave rise to a decrease in
the proportion of left-handed fibres from 24.9% to 21.4% and an increase in the
proportion of right-handed fibres from 25.5% to 26.0%. The modified perfusion and
coil setup offers better performance and control over cardiac contraction states.
We subsequently performed high-resolution diffusion spectrum imaging (DSI) and 3D
whole heart fibre tracking in fixed ex vivo rat hearts in slack state and
contracture. As a model-free method, DSI augmented the measurements of water
diffusion by also informing on multiple intra-voxel diffusion orientations and
non-Gaussian diffusion. This enabled us to identify the transition from right- to
left-handed fibres from the subendocardium to the subepicardium, as well as
voxels in apical regions that were traversed by multiple fibres. We observed that
both the mean generalised fractional anisotropy and mean kurtosis were lower in
hearts in contracture compared to the slack state, by 23% and 9.3%, respectively.
While its heavy acquisition burden currently limits the application of DSI in
vivo, ongoing work in acceleration techniques may enable its use in live animals
and patients. This would provide access to the as yet unexplored dimension of non
Gaussian diffusion that could serve as a highly sensitive marker of cardiac micro
structural integrity.
PMID- 25117497
TI - Images as drivers of progress in cardiac computational modelling.
AB - Computational models have become a fundamental tool in cardiac research. Models
are evolving to cover multiple scales and physical mechanisms. They are moving
towards mechanistic descriptions of personalised structure and function,
including effects of natural variability. These developments are underpinned to a
large extent by advances in imaging technologies. This article reviews how novel
imaging technologies, or the innovative use and extension of established ones,
integrate with computational models and drive novel insights into cardiac
biophysics. In terms of structural characterization, we discuss how imaging is
allowing a wide range of scales to be considered, from cellular levels to whole
organs. We analyse how the evolution from structural to functional imaging is
opening new avenues for computational models, and in this respect we review
methods for measurement of electrical activity, mechanics and flow. Finally, we
consider ways in which combined imaging and modelling research is likely to
continue advancing cardiac research, and identify some of the main challenges
that remain to be solved.
PMID- 25117504
TI - CT angiography after carotid artery stenting: assessment of the utility of
adaptive statistical iterative reconstruction and model-based iterative
reconstruction.
AB - INTRODUCTION: Follow-up CT angiography (CTA) is routinely performed for post
procedure management after carotid artery stenting (CAS). However, the stent
lumen tends to be underestimated because of stent artifacts on CTA reconstructed
with the filtered back projection (FBP) technique. We assessed the utility of new
iterative reconstruction techniques, such as adaptive statistical iterative
reconstruction (ASIR) and model-based iterative reconstruction (MBIR), for CTA
after CAS in comparison with FBP. METHODS: In a phantom study, we evaluated the
differences among the three reconstruction techniques with regard to the
relationship between the stent luminal diameter and the degree of underestimation
of stent luminal diameter. In a clinical study, 34 patients who underwent follow
up CTA after CAS were included. We compared the stent luminal diameters among
FBP, ASIR, and MBIR, and performed visual assessment of low attenuation area
(LAA) in the stent lumen using a three-point scale. RESULTS: In the phantom
study, stent luminal diameter was increasingly underestimated as luminal diameter
became smaller in all CTA images. Stent luminal diameter was larger with MBIR
than with the other reconstruction techniques. Similarly, in the clinical study,
stent luminal diameter was larger with MBIR than with the other reconstruction
techniques. LAA detectability scores of MBIR were greater than or equal to those
of FBP and ASIR in all cases. CONCLUSION: MBIR improved the accuracy of
assessment of stent luminal diameter and LAA detectability in the stent lumen
when compared with FBP and ASIR. We conclude that MBIR is a useful reconstruction
technique for CTA after CAS.
PMID- 25117503
TI - High prevalence of mismatch repair deficiency in prostate cancers diagnosed in
mismatch repair gene mutation carriers from the colon cancer family registry.
AB - The question of whether prostate cancer is part of the Lynch syndrome spectrum of
tumors is unresolved. We investigated the mismatch repair (MMR) status and
pathologic features of prostate cancers diagnosed in MMR gene mutation carriers.
Prostate cancers (mean age at diagnosis = 62 +/- SD = 8 years) from 32 MMR
mutation carriers (23 MSH2, 5 MLH1 and 4 MSH6) enrolled in the Australasian, Mayo
Clinic and Ontario sites of the Colon Cancer Family Registry were examined for
clinico-pathologic features and MMR-deficiency (immunohistochemical loss of MMR
protein expression and high levels of microsatellite instability; MSI-H). Tumor
MMR-deficiency was observed for 22 cases [69 %; 95 % confidence interval (CI) 50
83 %], with the highest prevalence of MMR-deficiency in tumors from MSH2 mutation
carriers (19/23, 83 %) compared with MLH1 and MSH6 carriers combined (3/9, 33 %;
p = 0.01). MMR-deficient tumors had increased levels of tumor infiltrating
lymphocytes compared with tumors without MMR-deficiency (p = 0.04). Under the
assumption that tumour MMR-deficiency occurred only because the cancer was caused
by the germline mutation, mutation carriers are at 3.2-fold (95 % CI 2.0-6.3)
increased risk of prostate cancer, and when assessed by gene, the relative risk
was greatest for MSH2 carriers (5.8, 95 % CI 2.6-20.9). Prostate cancer was the
first or only diagnosed tumor in 37 % of carriers. MMR gene mutation carriers
have at least a twofold or greater increased risk of developing MMR-deficient
prostate cancer where the risk is highest for MSH2 mutation carriers. MMR IHC
screening of prostate cancers will aid in identifying MMR gene mutation carriers.
PMID- 25117506
TI - Intake and macronutrient content of human milk given to extremely preterm
infants.
AB - BACKGROUND: Human milk (HM) is the preferred basis of nutrition for infants,
including those born prematurely. Information on HM macronutrient content is
necessary to optimize nutritional support of preterm infants. OBJECTIVES: This
study aimed to describe the types and amounts of enteral feeds given to Swedish
extremely preterm infants during hospitalization and to investigate the energy
and macronutrient contents in HM given to these infants. METHODS: A population
based study of Swedish extremely preterm infants (n = 586) born before 27
gestational weeks was conducted. Data on ingested volumes of different milk
during hospitalization and analyses of macronutrient content in HM samples were
obtained from hospital records. Nutritional content of HM was determined by mid
infrared spectrophotometry analysis. RESULTS: During the first 4 weeks of life,
99% of the infants were exclusively fed HM, and at 4 weeks of life, 70% of the
infants received only mother's own milk (MOM). Nutritional content in 821 MOM
samples was analyzed. Protein content in MOM decreased significantly from 2.2 to
1.2 g/100 mL during the first 112 postpartum days, whereas fat and energy content
were highly variable within and between MOM samples. In addition, 354 samples of
donor milk were analyzed. Content of protein, fat, and energy in pooled donor
milk (n = 129) was lower compared to single donor milk. CONCLUSION: Swedish
extremely preterm infants receive MOM to a large extent during hospitalization.
Protein, carbohydrates, and energy in MOM changed significantly with time. Weekly
analyses of MOM during the first month of lactation would allow more
individualized nutritional support for these vulnerable infants.
PMID- 25117505
TI - Sinupret activates CFTR and TMEM16A-dependent transepithelial chloride transport
and improves indicators of mucociliary clearance.
AB - INTRODUCTION: We have previously demonstrated that Sinupret, an established
treatment prescribed widely in Europe for respiratory ailments including
rhinosinusitis, promotes transepithelial chloride (Cl-) secretion in vitro and in
vivo. The present study was designed to evaluate other indicators of mucociliary
clearance (MCC) including ciliary beat frequency (CBF) and airway surface liquid
(ASL) depth, but also investigate the mechanisms that underlie activity of this
bioflavonoid. METHODS: Primary murine nasal septal epithelial (MNSE) [wild type
(WT) and transgenic CFTR(-/-)], human sinonasal epithelial (HSNE), WT CFTR
expressing CFBE and TMEM16A-expressing HEK cultures were utilized for the present
experiments. CBF and ASL depth measurements were performed. Mechanisms underlying
transepithelial Cl- transport were determined using pharmacologic manipulation in
Ussing chambers, Fura-2 intracellular calcium [Ca(2+)]i imaging, cAMP signaling,
regulatory domain (R-D) phosphorylation of CFTR, and excised inside out and whole
cell patch clamp analysis. RESULTS: Sinupret-mediated Cl- secretion
[DeltaISC(uA/cm(2))] was pronounced in WT MNSE (20.7+/-0.9 vs. 5.6+/
0.9(control), p<0.05), CFTR(-/-) MNSE (10.1+/-1.0 vs. 0.9+/-0.3(control), p<0.05)
and HSNE (20.7+/-0.3 vs. 6.4+/-0.9(control), p<0.05). The formulation activated
Ca(2+) signaling and TMEM16A channels, but also increased CFTR channel open
probability (Po) without stimulating PKA-dependent pathways responsible for
phosphorylation of the CFTR R-domain and resultant Cl- secretion. Sinupret also
enhanced CBF and ASL depth. CONCLUSION: Sinupret stimulates CBF, promotes
transepithelial Cl- secretion, and increases ASL depth in a manner likely to
enhance MCC. Our findings suggest that direct stimulation of CFTR, together with
activation of Ca(2+)-dependent TMEM16A secretion account for the majority of
anion transport attributable to Sinupret. These studies provide further rationale
for using robust Cl- secretagogue based therapies as an emerging treatment
modality for common respiratory diseases of MCC including acute and chronic
bronchitis and CRS.
PMID- 25117507
TI - Polymorphisms of E1 and GIGANTEA in wild populations of Lotus japonicus.
AB - In plants, timing of flowering is an essential factor that controls the survival
rates of descendants. The circadian clock genes E1 and GIGANTEA (GI) play a
central role in transmitting signals to flowering locus T (FT) in leguminous
plants. Lotus japonicus is a wild Japanese species that ranges from northern
Hokkaido to the southern Ryukyus and exhibits a wide range in terms of the time
between seeding and first flowering. In this study, we first identified LjGI and
analyzed polymorphisms of LjE1 and LjGI among wild populations covering the
entire distribution range of this species in Japan. LjGI had a coding sequence
(CDS) length of 3495 bp and included 14 exons. The homologies of DNA and amino
acid sequences between LjGI and GmGI were 89 and 88% (positive rate was 92%),
respectively. LjE1 harbored five nucleic acid changes in a 552 bp CDS, all of
which were nonsynonymous; four of the changes were located in the core function
area. LjE1 alleles exhibited partial north-south differentiation and non
neutrality. In contrast, the LjGI harbored one synonymous and one nonsynonymous
change. Thus, our study suggests that LjE1 may be involved in the control of
flowering times, whereas LjGI may be under strong purifying selection.
PMID- 25117509
TI - Toward absolute chemical composition distribution measurement of polyolefins by
high-temperature liquid chromatography hyphenated with infrared absorbance and
light scattering detectors.
AB - Chemical composition distribution (CCD) is a fundamental metric for representing
molecular structures of copolymers in addition to molecular weight distribution
(MWD). Solvent gradient interaction chromatography (SGIC) is commonly used to
separate copolymers by chemical composition in order to obtain CCD. The
separation of polymer in SGIC is, however, not only affected by chemical
composition but also by molecular weight and architecture. The ability to measure
composition and MW simultaneously after separation would be beneficial for
understanding the impact of different factors and deriving true CCD. In this
study, comprehensive two-dimensional chromatography (2D) was coupled with
infrared absorbance (IR5) and light scattering (LS) detectors for
characterization of ethylene-propylene copolymers. Polymers were first separated
by SGIC as the first dimension chromatography (D1). The separated fractions were
then characterized by the second dimension (D2) size exclusion chromatography
(SEC) with IR5 and LS detectors. The concentrations and compositions of the
separated fractions were measured online using the IR5 detector. The MWs of the
fractions were measured by the ratio of LS to IR5 signals. A metric was derived
from online concentration and composition data to represent CCD breadth. The
metric was shown to be independent of separation gradients for an "absolute"
measurement of CCD breadth. By combining online composition and MW data, the
relationship of MW as a function of chemical composition was obtained. This
relationship was qualitatively consistent with the results by SEC coupled to IR5,
which measures chemical composition as a function of logMW. The simultaneous
measurements of composition and MW give the opportunity to study the SGIC
separation mechanism and derive chain architectural characteristics of polymer
chains.
PMID- 25117508
TI - Two HSPs gene from juvenile Amur sturgeon (Acipenser schrenckii): cloning,
characterization and expression pattern to crowding and hypoxia stress.
AB - In this study, the cDNA sequences of HSP70 and HSP90 were isolated from the
special chondr-ganoid scale, Amur sturgeon, for the first time. Homology analysis
indicated that amino acid sequences of HSP70 and HSP90 shared high identity with
other species (82.68-99.07 and 90.19-98.07%, respectively). The tissue expression
analysis showed that the asHSP70 and asHSP90 mRNA were ubiquitously expressed in
all the examined tissues under unstressed condition. The expression pattern of
HSP70 and HSP90 under chronic (crowding) and acute (hypoxia) stress was examined
by q-PCR in liver, spleen and kidney. Results showed that stocking density could
significantly influence the expression of HSP70 at day 20 and/or day 40. In
contrast to stocking density, levels of HSP70 transcripts indicated a remarkable
increase in all examined tissues after hypoxia stress. HSP90 levels in liver and
spleen increased significantly in high stocking density. By comparison,
significant increase of asHSP90 in kidney was only found in high stocking density
at day 40. Similar to HSP70, the levels of HSP90 transcripts showed significant
increases after hypoxia stress except the transcript of liver in H2 group 6 h
after hypoxia. The assessment of asHSP70 and asHSP90 mRNA levels under crowding
and hypoxia stresses indicated that asHSP70 and asHSP90 gene might be good
indicators of stressful situations for Amur sturgeon. Taking serum globulin and
electrolytes account, we suggest that crowding and hypoxia stress can result in
considerable stress for Amur sturgeon.
PMID- 25117510
TI - Curcumin supplementation improves mitochondrial and behavioral deficits in
experimental model of chronic epilepsy.
AB - The present study was aimed to investigate the potential beneficial effect of
curcumin, a polyphenol with pleiotropic properties, on mitochondrial
dysfunctions, oxidative stress and cognitive deficits in a kindled model of
epilepsy. Kindled epilepsy was induced in rats by administering a sub-convulsive
dose of pentylenetetrazole (PTZ, 40 mg/kg body weight) every alternate day for 30
days. PTZ administered rats exhibited marked cognitive deficits assessed using
active and passive avoidance tasks. This was accompanied by a significant
decrease in NADH:cytochrome-c reductase (complex I) and cytochrome-c oxidase
(complex IV) activities along with an increase in ROS, lipid peroxidation and
protein carbonyls. The levels of glutathione also decreased in the cortex and
hippocampus. Electron micrographs revealed disruption of mitochondrial membrane
integrity with distorted cristae in PTZ treated animals. Histopathological
examination showed pyknotic nuclei and cell loss in the hippocampus as well as in
the cortex of PTZ treated animals. Curcumin administration at a dose of 100
mg/kg, p.o. throughout the treatment paradigm was able to ameliorate cognitive
deficits with no significant effect on seizure score. Curcumin was able to
restore the activity of mitochondrial complexes. In addition, significant
reduction in ROS generation, lipid peroxidation and protein carbonyls was
observed in PTZ animals supplemented with curcumin. Moreover, glutathione levels
were also restored in PTZ treated rats supplemented with curcumin. Curcumin
protected mitochondria from seizure induced structural alterations. Further, the
curcumin supplemented PTZ rats had normal cell morphology and reduced cell loss.
These results suggest that curcumin supplementation has potential to prevent
mitochondrial dysfunctions and oxidative stress with improved cognitive functions
in a chronic model of epilepsy.
PMID- 25117512
TI - Texture feature analysis for computer-aided diagnosis on pulmonary nodules.
AB - Differentiation of malignant and benign pulmonary nodules is of paramount
clinical importance. Texture features of pulmonary nodules in CT images reflect a
powerful character of the malignancy in addition to the geometry-related
measures. This study first compared three well-known types of two-dimensional
(2D) texture features (Haralick, Gabor, and local binary patterns or local binary
pattern features) on CADx of lung nodules using the largest public database
founded by Lung Image Database Consortium and Image Database Resource Initiative
and then investigated extension from 2D to three-dimensional (3D) space.
Quantitative comparison measures were made by the well-established support vector
machine (SVM) classifier, the area under the receiver operating characteristic
curves (AUC) and the p values from hypothesis t tests. While the three feature
types showed about 90% differentiation rate, the Haralick features achieved the
highest AUC value of 92.70% at an adequate image slice thickness, where a thinner
or thicker thickness will deteriorate the performance due to excessive image
noise or loss of axial details. Gain was observed when calculating 2D features on
all image slices as compared to the single largest slice. The 3D extension
revealed potential gain when an optimal number of directions can be found. All
the observations from this systematic investigation study on the three feature
types can lead to the conclusions that the Haralick feature type is a better
choice, the use of the full 3D data is beneficial, and an adequate tradeoff
between image thickness and noise is desired for an optimal CADx performance.
These conclusions provide a guideline for further research on lung nodule
differentiation using CT imaging.
PMID- 25117513
TI - Fetal echocardiography has a role in multimodality imaging for surgical planning.
PMID- 25117514
TI - Saccharomyces cerevisiae Gpi2, an accessory subunit of the enzyme catalyzing the
first step of glycosylphosphatidylinositol (GPI) anchor biosynthesis, selectively
complements some of the functions of its homolog in Candida albicans.
AB - GPI2 encodes for one of the six accessory subunits of the GPI-N
acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the first step of
GPI biosynthesis in S. cerevisiae and C. albicans. It has been previously
reported in S. cerevisiae that this subunit physically interacts with and
negatively modulates Ras signaling. On the other hand, studies from our lab have
shown that the homologous subunit in C. albicans is a positive modulator of Ras
signaling. Are the functions of this subunit therefore strictly species
dependent? We present here functional complementation studies on GPI2 from S.
cerevisiae and C. albicans that were carried out to address this issue.
Expression of CaGPI2 in a ScGPI2 conditional lethal mutant could not restore its
growth defects. Likewise, ScGPI2 overexpression in a CaGPI2 heterozygous mutant
could not restore its deficient GPI-GnT activity or reverse defects in its cell
wall integrity and could only poorly restore filamentation. However,
interestingly, ScGPI2 could restore lanosterol demethylase (CaERG11) levels and
reverse azole resistance of the CaGPI2 heterozygote. It appeared to do this by
regulating levels of another GPI-GnT subunit, CaGPI19, which we have previously
shown to be involved in cross-talk with CaERG11. Thus, the effect of CaGPI2 on
sterol biosynthesis in C. albicans is independent of its interaction with the GPI
GnT complex and Ras signaling pathways. In addition, the interaction of Gpi2 with
other subunits of the GPI-GnT complex as well as with Ras signaling appears to
have evolved differently in the two organisms.
PMID- 25117515
TI - Flexibility and mutagenic resiliency of glycosyltransferases.
AB - The human blood group A and B antigens are synthesized by two highly homologous
enzymes, glycosyltransferase A (GTA) and glycosyltransferase B (GTB),
respectively. These enzymes catalyze the transfer of either GalNAc or Gal from
their corresponding UDP-donors to alphaFuc1-2betaGal-R terminating acceptors. GTA
and GTB differ at only four of 354 amino acids (R176G, G235S, L266M, G268A),
which alter the donor specificity from UDP-GalNAc to UDP-Gal. Blood type O
individuals synthesize truncated or non-functional enzymes. The cloning,
crystallization and X-ray structure elucidations for GTA and GTB have revealed
key residues responsible for donor discrimination and acceptor binding.
Structural studies suggest that numerous conformational changes occur during the
catalytic cycle. Over 300 ABO alleles are tabulated in the blood group antigen
mutation database (BGMUT) that provides a framework for structure-function
studies. Natural mutations are found in all regions of GTA and GTB from the
active site, flexible loops, stem region and surfaces remote from the active
site. Our characterizations of natural mutants near a flexible loop (V175M), on a
remote surface site (P156L), in the metal binding motif (M212V) and near the
acceptor binding site (L232P) demonstrate the resiliency of GTA and GTB to
mutagenesis.
PMID- 25117517
TI - Calibration-free ionophore-based ion-selective electrodes with a Co(II)/Co(III)
redox couple-based solid contact.
AB - A high electrode-to-electrode reproducibility of the emf response of solid
contact ion-selective electrodes (SC-ISEs) requires a precise control of the
phase boundary potential between the ion-selective membrane (ISM) and the
underlying electron conductor. To achieve this, we introduced previously
ionophore-free ion exchanger membranes doped with a well controlled ratio of
oxidized and reduced species of a redox couple as redox buffer and used them to
make SC-ISEs that exhibited highly reproducible electrode-to-electrode
potentials. Unfortunately, ionophores were found to promote the loss of
insufficiently lipophilic species from the ionophore-doped ISMs into aqueous
samples. Here we report on an improved redox buffer platform based on equimolar
amounts of the much less hydrophilic Co(III) and Co(II) complexes of 4,4'-dinonyl
2,2'-bipyridyl, which makes it possible to extend the redox buffer approach to
ionophore-based ISEs. For example, K(+)-selective electrodes based on the
ionophore valinomycin exhibit electrode-to-electrode standard deviations as low
as 0.7 mV after exposure of freshly prepared electrodes for 1 h to aqueous
solutions. Exposure of freshly prepared ISE membranes to humidity prior to their
first contact to electrolyte solution minimizes the initial (reproducible) emf
drift. This redox buffer has also been successfully applied to sodium, potassium,
calcium, hydrogen, and carbonate ion-selective electrodes, which all exhibit the
high selectivity over interfering ions as expected for ionophore-doped ISE
membranes.
PMID- 25117516
TI - Elucidation of a protein-protein interaction network involved in Corynebacterium
glutamicum cell wall biosynthesis as determined by bacterial two-hybrid analysis.
AB - Mycobacterium species have a highly complex and unique cell wall that consists of
a large macromolecular structure termed the mycolyl-arabinogalactan-peptidoglycan
(mAGP) complex. This complex is essential for growth, survival and virulence of
the human pathogen Mycobacterium tuberculosis, and is the target of several anti
tubercular drugs. The closely related species Corynebacterium glutamicum has
proven useful in the study of orthologous M. tuberculosis genes and proteins
involved in mAGP synthesis. This study examines the construction of a protein
protein interaction network for the major cell wall component arabinogalactan in
C. glutamicum based on the use of a bacterial two-hybrid system. We have
identified twenty-four putative homotypic and heterotypic protein interactions in
vivo. Our results demonstrate an association between glycosyltransferases, GlfT1
and AftB, and interaction between the sub-units of decaprenylphosphoribose
epimerase, DprE1 and DprE2. These analyses have also shown that AftB interacts
with AftA, which catalyzes the addition of the first three arabinose units onto
the galactan chain. Both AftA and AftB associate with other
arabinofuranosyltransferases, including Emb and AftC, that elongate and branch
the arabinan domain. Moreover, a number of proteins involved in arabinogalactan
biosynthesis were shown to form dimers or multimers. These findings provide a
useful recourse for understanding the biosynthesis and function of the
mycobacterial cell wall, as well as providing new therapeutic targets.
PMID- 25117519
TI - Support for a tobacco endgame strategy in 18 European countries.
AB - OBJECTIVE: The feasibility of a tobacco endgame strategy, aiming to bring smoking
prevalence to near-zero levels, is currently under debate. We provide information
on public support for such a strategy in Europe. METHODS: In 2010 we conducted a
face-to-face representative survey in 18 European countries (Albania, Austria,
Bulgaria, the Czech Republic, Croatia, England, Finland, France, Greece, Hungary,
Ireland, Italy, Latvia, Poland, Portugal, Romania, Spain and Sweden). The present
analysis is based on 16,947 individuals aged >= 15 years providing information on
their attitudes towards a complete ban on the use or sale of tobacco. RESULTS:
Overall, 34.9% of adults (32.8% in men and 37.0% in women; p<0.001) supported a
complete ban strategy on use or sale of tobacco, 41.2% of never, 29.4% of ex- and
25.6% of current smokers. The highest support was observed in southern Europe
(42.5%), followed by eastern (39.1%), northern (27.5%) and western Europe (23.0%;
p<0.001). A significant inverse trend was observed with both age and education.
CONCLUSION: Approximately one in three adults (and one in four smokers) supports
a comprehensive tobacco endgame intervention. This first study in Europe provides
a baseline for evaluating future trends in public support for extreme
propositions to end or drastically cut smoking.
PMID- 25117518
TI - Whole organism high content screening identifies stimulators of pancreatic beta
cell proliferation.
AB - Inducing beta-cell mass expansion in diabetic patients with the aim to restore
glucose homeostasis is a promising therapeutic strategy. Although several in
vitro studies have been carried out to identify modulators of beta-cell mass
expansion, restoring endogenous beta-cell mass in vivo has yet to be achieved. To
identify potential stimulators of beta-cell replication in vivo, we established
transgenic zebrafish lines that monitor and allow the quantification of cell
proliferation by using the fluorescent ubiquitylation-based cell cycle indicator
(FUCCI) technology. Using these new reagents, we performed an unbiased chemical
screen, and identified 20 small molecules that markedly increased beta-cell
proliferation in vivo. Importantly, these structurally distinct molecules, which
include clinically-approved drugs, modulate three specific signaling pathways:
serotonin, retinoic acid and glucocorticoids, showing the high sensitivity and
robustness of our screen. Notably, two drug classes, retinoic acid and
glucocorticoids, also promoted beta-cell regeneration after beta-cell ablation.
Thus, this study establishes a proof of principle for a high-throughput small
molecule-screen for beta-cell proliferation in vivo, and identified compounds
that stimulate beta-cell proliferation and regeneration.
PMID- 25117520
TI - How personalized medical data could improve health care.
AB - We present a redesign of medical test results by placing the information of blood
samples in the context of the patient's personal clinical data. We predict that
implementing personalized data in the treatment of patients will promote
engagement in the treatment, motivate patients to take responsibility and lead to
greater satisfaction with the patient-doctor relationship.
PMID- 25117521
TI - Patient and physician gender concordance in preventive care in university primary
care settings.
AB - OBJECTIVE: To assess the quality of preventive care according to physician and
patient gender in a country with universal health care coverage. METHODS: We
assessed a retrospective cohort study of 1001 randomly selected patients aged 50
80 years followed over 2 years (2005-2006) in 4 Swiss university primary care
settings (Basel, Geneva, Lausanne, Zurich). We used indicators derived from
RAND's Quality Assessment Tools and examined percentages of recommended
preventive care. Results were adjusted using hierarchical multivariate logistic
regression models. RESULTS: 1001 patients (44% women) were followed by 189
physicians (52% women). Female patients received less preventive care than male
patients (65.2% vs. 72.1%, p<0.001). Female physicians provided significantly
more preventive care than male physicians (p=0.01) to both female (66.7% vs.
63.6%) and male patients (73.4% vs. 70.7%). After multivariate adjustment,
differences according to physician (p=0.02) and patient gender (p<0.001) remained
statistically significant. Female physicians provided more recommended cancer
screening than male physicians (78.4 vs. 71.9%, p=0.01). CONCLUSIONS: In Swiss
university primary care settings, female patients receive less preventive care
than male patients, with female physicians providing more preventive care than
male physicians. Greater attention should be paid to female patients in
preventive care and to why female physicians tend to provide better preventive
care.
PMID- 25117522
TI - Understanding occupational sitting: prevalence, correlates and moderating effects
in Australian employees.
AB - OBJECTIVE: To (1) compare occupational sitting between different socio
demographic, health-related, work-related and psychosocial categories, (2)
identity socio-demographic, health-related, work-related and psychosocial
correlates of occupational sitting, and (3) examine the moderating effect of work
related factors in the relation between correlates and occupational sitting.
METHODS: Randomly-selected Australian adults completed a web-based survey
assessing socio-demographic (country of birth, gender, age, education, income),
health-related (general health, weight, physical activity), work-related
(employment status, occupational task, occupational classification) and sedentary
specific psychosocial (social norm, social support, self-efficacy, control,
advantages, disadvantage, intention) factors, and occupational sitting-time. t
tests, ANOVAs and multiple linear regression analyses were conducted (in 2013) on
a sample of employees (n=993). RESULTS: Respondents sat on average for 3.75
(SD=2.45) h/day during work. Investigated correlates explained 41% of the
variance in occupational sitting. More occupational sitting was associated with
being male, being younger, higher education and income, part-time and full-time
employment, sedentary job tasks, white-collar/professional occupations, higher
BMI, and perceiving more advantages of sitting less at work. Employment status
and occupational classification moderated the association between control to sit
less and occupational sitting. A lack of control to sit less was associated with
higher occupational sitting in part-time and full-time workers, but not in casual
workers; and in white-collar and professional workers, but not in blue-collar
workers. CONCLUSIONS: Most important contributors to occupational sitting were
work-related and socio-demographic correlates. More research is needed to confirm
present results.
PMID- 25117523
TI - The status of men's health in Asia.
AB - OBJECTIVES: This study aims to compare health status and its risk factors between
men and women who are from countries of different income status in Asia. METHOD:
We have included 47 Asian countries and 2 regions in this study. Life expectancy,
mortality rate from communicable disease, non-communicable disease and injuries,
the prevalence of non-communicable diseases risk factors and their trends were
extracted from the WHO and respective governmental database. Subgroup analysis
was performed based on country income groups. RESULTS: Overall, men have shorter
life expectancy and higher mortality rates compared to women. Men from higher
income countries lived longer compared to men from lower-income countries. There
is a wide variation of male life expectancy in upper and lower middle income
countries. The mean systolic blood pressure, fasting blood glucose and body mass
index in Asia have also increased over the years. CONCLUSION: This study confirms
that Asian men have poorer health compared to women besides the growing concerns
on NCD risk factors. The findings from this study calls for a concerted effort to
find solutions in addressing men's health problems in Asia.
PMID- 25117524
TI - Dog walking is associated with more outdoor play and independent mobility for
children.
AB - OBJECTIVE: Dog ownership is positively associated with children's physical
activity. It is plausible that dog-facilitated activity rather than dog ownership
per se encourages children's physical activity behaviors. We examined
relationships between dog walking and children's physical activity, and outdoor
play and independent mobility. METHOD: Cross-sectional survey data from the 2007
Perth (Western Australia) TRavel, Environment, and Kids (TREK) project were
analyzed for 727 10-12 year olds with a family dog. Weekly minutes of overall
physical activity and walking, local walking and outdoor play were collected from
children and parents. Children's weekly pedometer steps were measured.
Independent mobility was determined by active independent travel to 15 local
destinations. RESULTS: Overall, 55% of children walked their dog. After
adjustment, more dog walkers than non-dog walkers walked in the neighborhood (75%
vs. 47%), played in the street (60% vs. 45%) and played in the yard (91% vs. 84%)
(all p <= 0.05). Dog walkers were more independently mobile than non-dog walkers
(p <= 0.001). Dog walking status was not associated with overall physical
activity, walking, or pedometer steps (p>0.05). CONCLUSIONS: Dog-facilitated play
and physical activity can be an effective strategy for increasing children's
physical activity. Dog walking may provide a readily accessible and safe option
for improving levels of independent mobility.
PMID- 25117525
TI - Moving toward implementation: the potential for accountable care organizations
and private-public partnerships to advance active neighborhood design.
AB - The 2010 Affordable Care Act's (ACA) aims of lowering costs and improving quality
of care will renew focus on preventive health strategies. This coincides with a
trend in medicine to reconsider population health approaches as part of the
standard curriculum. This intersection of new policy and educational climates
presents a unique opportunity to reconsider traditional healthcare structures.
This paper introduces and advances an alignment that few have considered. We
propose that accountable care organizations (ACOs), which are expected to
proliferate under the ACA, present the best opportunity to establish partnerships
between healthcare, public health, and community-based organizations to achieve
the legislation's goals. One example is encouraging daily physical activity via
built environment interventions and programs, which is recommended by numerous
groups. We highlight how nonprofit organizations in Sacramento, California have
been able to leverage influence, capital, and policy to encourage design for
active living, and how their work is coordinating with public health and
healthcare initiatives. In conclusion, we critically examine potential barriers
to the success of partnerships between ACOs and community organizations and
encourage further exploration and evaluation.
PMID- 25117526
TI - Building safety into active living initiatives.
AB - OBJECTIVE: Efforts to promote environmental designs that facilitate opportunities
for physical activity should consider the fact that injuries are the leading
cause of death for Americans ages 1 to 44, with transportation-related injuries
the most common cause. Drawing on the latest research and best practices in the
field of injury prevention, the purpose of this article is to provide those
working to promote physical activity with evidence-based recommendations on
building in safety while designing active environments. METHOD: A systematic
review of the peer-reviewed and grey literature published from 1995 to 2012 was
conducted to identify injury prevention strategies applicable to objectives in
the Active Design Guidelines (ADG), which present design strategies for active
living. Injury prevention strategies were rated according to the strength of the
research evidence. RESULTS: We identified 18 urban design strategies and 9
building design strategies that promote safety. Evidence was strong or emerging
for 14/18 urban design strategies and 7/9 building design strategies. CONCLUSION:
ADG strategies are often wholly compatible with well-accepted injury prevention
principles. By partnering with architects and planners, injury prevention and
public health professionals can help ensure that new and renovated spaces
maximize both active living and safety.
PMID- 25117528
TI - Quality criteria for health checks: development of a European consensus
agreement.
AB - OBJECTIVE: Health checks may empower individuals to take better care of their
health, but they may incorporate risks of incorrect test results, overdiagnosis
and overtreatment as well. Some health checks are strictly regulated, such as in
many of the national screening programs, but the ones offered outside such
programs and in the commercial domain, are not. We developed a European consensus
agreement for quality criteria. METHOD: Quality criteria were developed with the
contribution of 43 experts from 16 European countries and 8 European
organizations. A working group drafted a proposal, which was revised in several
rounds of internal and external review by a multidisciplinary group of experts.
RESULT: The quality criteria address the provision of information, communication
and informed consent, predictive ability and utility of the test, and quality
assurance. CONCLUSION: The consensus agreement on the quality of health checks
aim to enhance informed decision making in clients and protects the affordability
of the health care system. The criteria can be developed further into a formal
standard and regulation if such authority is warranted.
PMID- 25117527
TI - Distinct associations of different sedentary behaviors with health-related
attributes among older adults.
AB - OBJECTIVE: Leisure-time sedentary behaviors (LTSBs) have been associated
adversely with health outcomes. However, limited research has focused on
different categories of LTSB. We aimed at identifying categories of LTSBs and
examining their separate associations with indices of health among Japanese older
adults. METHODS: A postal survey collected data on self-reported health,
psychological distress, body mass index, moderate-to-vigorous physical activity
(MVPA), LTSBs (five behaviors) and socio-demographic characteristics from 1,580
Japanese older adults (67% response rate; 65-74 years) in 2010. Exploratory
factor analysis was used to classify LTSBs. Odds ratios (ORs) were calculated for
associations of LTSB categories with self-reported health, psychological
distress, overweight, and lower MVPA. Data were analyzed in 2013. RESULTS: Two
categories of LTSB: passive sedentary time (consisting of TV time, listening or
talking while sitting, and sitting around) and mentally-active sedentary time
(consisting of computer-use and reading books or newspapers) were identified.
Higher passive sedentary time was associated with a higher odds of being
overweight (OR: 1.39, [95% CI: 1.08-1.80]), and lower MVPA (1.26, [1.02-1.54]).
Higher mentally-active sedentary time was associated with lower odds of lower
MVPA (0.70, [0.57-0.86]). CONCLUSIONS: Two types of sedentary time-passive and
mentally-active-may play different roles in older adults' well-being.
PMID- 25117529
TI - Sesamin suppresses macrophage-derived chemokine expression in human monocytes via
epigenetic regulation.
AB - BACKGROUND: Chemokines play important roles in the pathogenesis of asthmatic
inflammation. Sesamin, a class of phytoestrogen isolated from sesame seed Sesamum
indicum, is recently regarded as an anti-inflammatory agent. However, the effects
of sesamin on asthma-related chemokines are unknown. To this end, we investigated
the effects of sesamin on the expression interferon-gamma-inducible protein-10
(IP-10/CXCL10), macrophage-derived chemokine (MDC/CCL22), growth-related oncogene
alpha (GRO-alpha/CXCL1) and tumor necrosis factor (TNF)-alpha in human monocytes.
METHODS: Cells were pretreated with sesamin before lipopolysaccharide (LPS)
stimulation. IP-10, MDC, GRO-alpha and TNF-alpha were measured by ELISA. Involved
receptors and intracellular signaling were investigated by receptor antagonists,
pathway inhibitors, western blotting and chromatin immunoprecipitation. RESULTS:
Sesamin suppressed LPS-induced MDC in THP-1 and human primary monocytes. Sesamin
suppressed LPS-induced IP-10 in THP-1 cells, but not human primary monocytes.
Sesamin had no effects on LPS-induced GRO-alpha and TNF-alpha expression in THP-1
and human primary monocytes. The suppressive effect of sesamin on MDC was
reversed by the estrogen receptor (ER) and peroxisomal proliferator-activated
receptor (PPAR)-alpha antagonists. Sesamin suppressed LPS-induced phosphorylation
of mitogen-activated protein kinase (MAPK)-p38 and nuclear factor kappa B
(NFkappaB)-p65. Sesamin suppressed histone H3/H4 acetylation in the MDC promoter
region. CONCLUSION: Sesamin suppressed LPS-induced MDC expression via the ER, the
PPAR-alpha, the MAPK-p38 pathway, the NFkappaB-p65 pathway and the epigenetic
regulation. Sesamin may have therapeutic potential in preventing and treating
asthma.
PMID- 25117530
TI - Dynamically optimizing experiment schedules of a laboratory robot system with
simulated annealing.
AB - A scheduler has been developed for an integrated laboratory robot system that
operates in an always-on mode. The integrated system is designed for imaging
plates containing protein crystallization experiments, and it allows
crystallographers to enter plates at any time and request that they be imaged at
multiple time points in the future. The scheduler must rearrange tasks within the
time it takes to image one plate, trading off the quality of the schedule for the
speed of the computation. For this reason, the scheduler was based on a simulated
annealing algorithm with an objective function that makes use of a linear
programming solver. To optimize the scheduler, extensive computational
simulations were performed involving a difficult but representative scheduling
problem. The simulations explore multiple configurations of the simulated
annealing algorithm, including both geometric and adaptive annealing schedules, 3
neighborhood functions, and 20 neighborhood diameters. An optimal configuration
was found that produced the best results in less than 60 seconds, well within the
window necessary to dynamically reschedule imaging tasks as new plates are
entered into the system.
PMID- 25117532
TI - The ecology of yeasts in the bark beetle holobiont: a century of research
revisited.
AB - Yeasts are extremely common associates of scolytine bark beetles, yet the basic
ecology of yeasts in the bark beetle holobiont remains poorly understood. Yeasts
are present in all beetle life stages and consistently isolated from adult,
larval, and pupal integuments and mycangial structures, but yeasts are also found
in oviposition galleries, pupal chambers, larval and adult digestive tracts, as
well as phloem and xylem tissues. Yeasts in the Saccharomycetaceae family are the
most prevalent associates, and most individual beetles are associated with only
one or several yeast species. Kuraishia capsulata and Ogataea pini are the most
commonly encountered yeast species in surveys of Dendroctonus and Ips beetles;
most beetles that have been surveyed are vectors for one or both yeasts. Yeasts
have significant but often overlooked functional roles in bark beetle ecology.
Infochemicals resulting from volatile production by yeast have wide-ranging
bioactivity for arthropods: Yeast emissions attract beetles at low concentrations
but repel beetles at high concentrations, and yeast emissions can also serve as
cues to predators and parasites of bark beetles. In some cases, yeasts can modify
tree chemistry over time or metabolize toxic terpenoids, though potential
consequences for beetle performance or the growth of nutritional fungi remain to
be demonstrated. Also, the presence of yeast species can restrict or promote the
establishment and growth of filamentous fungi, including mutualists,
entomopathogens, and opportunistic saprophytes. The role of yeasts as nutritional
symbionts has received mixed support, though a nutritional hypothesis has not
been extensively tested. Continued research on the functional ecology of bark
beetle-yeast associations is needed to better understand the emergent properties
of these complex symbiont assemblages.
PMID- 25117533
TI - Label-free colorimetric detection of cadmium ions in rice samples using gold
nanoparticles.
AB - A simple and label-free colorimetric method for cadmium ions (Cd(2+)) detection
using unmodified gold nanoparticles (AuNPs) is reported. The unmodified AuNPs
easily aggregate in a high concentration of NaCl solution, but the presence of
glutathione (GSH) can prevent the salt-induced aggregation of AuNPs. When Cd(2+)
is added to the stable mixture of AuNPs, GSH, and NaCl, Cd(2+) can coordinate
with 4* GSH as a spherical shaped complex, which decreases the amount of free GSH
on the surface of gold nanoparticles to weaken the stability of AuNPs, and AuNPs
will easily aggregate in high-salt conditions. On the basis of the mechanism, we
design a simple, label-free colorimetric method using AuNPs accompanied by GSH in
a high-salt environment to detect Cd(2+) in water and digested rice samples.
PMID- 25117531
TI - Endophytic fungi: expanding the arsenal of industrial enzyme producers.
AB - Endophytic fungi, mostly belonging to the Ascomycota, are found in the
intercellular spaces of the aerial plant parts, particularly in leaf sheaths,
sometimes even within the bark and root system without inducing any visual
symptoms of their presence. These fungi appear to have a capacity to produce a
wide range of enzymes and secondary metabolites exhibiting a variety of
biological activities. However, they have been only barely exploited as sources
of enzymes of industrial interest. This review emphasizes the suitability and
possible advantages of including the endophytic fungi in the screening of new
enzyme producing organisms as well as in studies aiming to optimize the
production of enzymes through well-known culture processes. Apparently endophytic
fungi possess the two types of extracellular enzymatic systems necessary to
degrade the vegetal biomass: (1) the hydrolytic system responsible for
polysaccharide degradation consisting mainly in xylanases and cellulases; and (2)
the unique oxidative ligninolytic system, which degrades lignin and opens phenyl
rings, comprises mainly laccases, ligninases and peroxidases. The obvious ability
of endophytic fungi to degrade the complex structure of lignocellulose makes them
useful in the exploration of the lignocellulosic biomass for the production of
fuel ethanol and other value-added commodity chemicals. In addition to this,
endophytic fungi may become new sources of industrially useful enzymes such as
lipases, amylases and proteases.
PMID- 25117535
TI - The energy allocation function of sleep: a unifying theory of sleep, torpor, and
continuous wakefulness.
AB - The energy allocation (EA) model defines behavioral strategies that optimize the
temporal utilization of energy to maximize reproductive success. This model
proposes that all species of the animal kingdom share a universal sleep function
that shunts waking energy utilization toward sleep-dependent biological
investment. For endotherms, REM sleep evolved to enhance energy appropriation for
somatic and CNS-related processes by eliminating thermoregulatory defenses and
skeletal muscle tone. Alternating REM with NREM sleep conserves energy by
decreasing the need for core body temperature defense. Three EA phenotypes are
proposed: sleep-wake cycling, torpor, and continuous (or predominant)
wakefulness. Each phenotype carries inherent costs and benefits. Sleep-wake
cycling downregulates specific biological processes in waking and upregulates
them in sleep, thereby decreasing energy demands imposed by wakefulness, reducing
cellular infrastructure requirements, and resulting in overall energy
conservation. Torpor achieves the greatest energy savings, but critical
biological operations are compromised. Continuous wakefulness maximizes niche
exploitation, but endures the greatest energy demands. The EA model advances a
new construct for understanding sleep-wake organization in ontogenetic and
phylogenetic domains.
PMID- 25117534
TI - Detection of Kaposi's sarcoma associated herpesvirus nucleic acids using a
smartphone accessory.
AB - Kaposi's sarcoma (KS) is an infectious cancer occurring in immune-compromised
patients, caused by Kaposi's sarcoma associated herpesvirus (KSHV). Our vision is
to simplify the process of KS diagnosis through the creation of a smartphone
based point-of-care system capable of yielding an actionable diagnostic readout
starting from a raw biopsy sample. In this work we develop the sensing mechanism
for the overall system, a smartphone accessory capable of detecting KSHV nucleic
acids. The accessory reads out microfluidic chips filled with a colorimetric
nanoparticle assay targeted at KSHV. We calculate that our final device can read
out gold nanoparticle solutions with an accuracy of 0.05 OD, and we demonstrate
that it can detect DNA sequences from KSHV down to 1 nM. We believe that through
integration with our previously developed components, a smartphone based system
like the one studied here can provide accurate detection information, as well as
a simple platform for field based clinical diagnosis and research.
PMID- 25117536
TI - Soft perforation of cardiolipin-containing planar lipid bilayer membrane by
cytochrome c and H(2)O(2).
AB - The release of cytochrome c (cyt c) from mitochondria is responsible for
initiation of cell apoptosis. Although extramitochondrial proteins are thought to
initiate this release, the exact mechanism remains unclear. Cyt c binds to and
penetrates lipid bilayer membranes of specific phospholipid cardiolipin (CL)
contained in mitochondria. We present here the experimental results of monitoring
planar BLM (pBLM) from mixtures of azolectin and of CL (4/1 by moles) by triangle
voltage pulses of 100 mV in amplitude and frequency of 2 Hz. The BLM were
modified by a successive addition of cyt c and of H(2)O(2) in water solution. It
is shown that the addition of cyt c alone leads to a stepwise increase in the
ionic conductance of the pBLM, indicating the appearance of transmembrane pores.
Pore lifetimes then reached several seconds at an average pore diameter of ~2 nm.
Current-voltage characteristics were then linear and passed through the origin
which is characteristic for broad, nonselective ion pores. Subsequent addition of
H(2)O(2) caused a dramatic increase in transmembrane current at retention of
average pore size constant. Observed increase in membrane current is due to
growth of a number of pores in an open state. We suggest that hydrogen peroxide
in the presence of cyt c promotes a peroxidation of membrane phospholipids to
form lysolipids, the embedding of which stabilizes the edge of the pore and the
surface of lipid bilayer.
PMID- 25117539
TI - First report of a direct surface plasmon resonance immunosensor for a small
molecule seafood toxin.
AB - Tetrodotoxin (TTX), a small molecular weight neurotoxin, is responsible for
poisoning events that traditionally occur from consumption of contaminated puffer
fish. Recent studies have shown a growing number of foods contaminated with TTX
and a larger number of waters and associated countries where the toxin may occur.
The apparent expanding prevalence of TTX supports a growing need for screening
assays that can be used to detect potentially harmful food. In the past few
years, surface plasmon resonance (SPR) biosensors have been developed for rapid,
robust detection of TTX; however, these assays focus on detection of unbound
antibody from an inhibition reaction with the toxin. This manuscript introduces
the first direct immunoassay for a seafood toxin, specifically TTX. Major
advantages of this assay compared to indirect assays include increased speed of
analysis, decreased use of biological reagents, and improved confidence in the
detection of the toxin, along with the ability to characterize the antibody/toxin
interaction. The analytical method introduced in this paper could be applied to
other seafood toxins, as well as to a wide range of low molecular weight targets.
PMID- 25117538
TI - Getting Black Men to Undergo Prostate Cancer Screening: The Role of Social
Capital.
AB - Despite higher rates of prostate cancer-related mortality and later stage of
prostate cancer diagnosis, Black/African American men are significantly less
likely than non-Hispanic White men to use early detection screening tools, like
prostate-specific antigen (PSA) testing for prostate cancer. Lower screening
rates may be due, in part, to controversy over the value of prostate cancer
screenings as part of routine preventive care for men, but Black men represent a
high-risk group for prostate cancer that may still benefit from PSA testing.
Exploring the role of social factors that might be associated with PSA testing
can increase knowledge of what might promote screening behaviors for prostate
cancer and other health conditions for which Black men are at high risk. Using
multilevel logistic regression, this study analyzed self-report lifetime use of
PSA test for 829 Black men older than 45 years across 381 Philadelphia census
tracts. This study included individual demographic and aggregated social capital
data from the Public Health Management Corporation's 2004, 2006, and 2008 waves
of the Community Health Database, and sociodemographic characteristics from the
2000 U.S. Census. Each unit increase in community participation was associated
with a 3 to 3.5 times greater likelihood of having had a PSA test (odds ratio =
3.35). Findings suggest that structural forms of social capital may play a role
in screening behaviors for Black men in Philadelphia. A better understanding of
the mechanism underlying the link between social capital and screening behaviors
can inform how researchers and interventionists develop tools to promote
screening for those who need it.
PMID- 25117537
TI - Tannic acid modified silver nanoparticles show antiviral activity in herpes
simplex virus type 2 infection.
AB - The interaction between silver nanoparticles and herpesviruses is attracting
great interest due to their antiviral activity and possibility to use as
microbicides for oral and anogenital herpes. In this work, we demonstrate that
tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are
capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral
activity of tannic acid modified silver nanoparticles was size-related, required
direct interaction and blocked virus attachment, penetration and further spread.
All tested tannic acid modified silver nanoparticles reduced both infection and
inflammatory reaction in the mouse model of HSV-2 infection when used at
infection or for a post-infection treatment. Smaller-sized nanoparticles induced
production of cytokines and chemokines important for anti-viral response. The
corresponding control buffers with tannic acid showed inferior antiviral effects
in vitro and were ineffective in blocking in vivo infection. Our results show
that tannic acid modified silver nanoparticles are good candidates for
microbicides used in treatment of herpesvirus infections.
PMID- 25117543
TI - An integrative computational model for large-scale identification of
metalloproteins in microbial genomes: a focus on iron-sulfur cluster proteins.
AB - Metalloproteins represent a ubiquitous group of molecules which are crucial to
the survival of all living organisms. While several metal-binding motifs have
been defined, it remains challenging to confidently identify metalloproteins from
primary protein sequences using computational approaches alone. Here, we describe
a comprehensive strategy based on a machine learning approach to design and
assess a penalized generalized linear model. We used this strategy to detect
members of the iron-sulfur cluster protein family. A new category of descriptors,
whose profile is based on profile hidden Markov models, encoding structural
information was combined with public descriptors into a linear model. The model
was trained and tested on distinct datasets composed of well-characterized iron
sulfur protein sequences, and the resulting model provided higher sensitivity
compared to a motif-based approach, while maintaining a good level of
specificity. Analysis of this linear model allows us to detect and quantify the
contribution of each descriptor, providing us with a better understanding of this
complex protein family along with valuable indications for further experimental
characterization. Two newly-identified proteins, YhcC and YdiJ, were functionally
validated as genuine iron-sulfur proteins, confirming the prediction. The
computational model was then applied to over 550 prokaryotic genomes to screen
for iron-sulfur proteomes; the results are publicly available at: . This study
represents a proof-of-concept for the application of a penalized linear model to
identify metalloprotein superfamilies on a large-scale. The application employed
here, screening for iron-sulfur proteomes, provides new candidates for further
biochemical and structural analysis as well as new resources for an extensive
exploration of iron-sulfuromes in the microbial world.
PMID- 25117541
TI - Human premotor areas parse sequences into their spatial and temporal features.
AB - Skilled performance is characterized by precise and flexible control of movement
sequences in space and time. Recent theories suggest that integrated spatio
temporal trajectories are generated by intrinsic dynamics of motor and premotor
networks. This contrasts with behavioural advantages that emerge when a trained
spatial or temporal feature of sequences is transferred to a new spatio-temporal
combination arguing for independent neural representations of these sequence
features. We used a new fMRI pattern classification approach to identify brain
regions with independent vs integrated representations. A distinct regional
dissociation within motor areas was revealed: whereas only the contralateral
primary motor cortex exhibited unique patterns for each spatio-temporal sequence
combination, bilateral premotor areas represented spatial and temporal features
independently of each other. These findings advocate a unique function of higher
motor areas for flexible recombination and efficient encoding of complex motor
behaviours.
PMID- 25117540
TI - The transcription factor NRSF contributes to epileptogenesis by selective
repression of a subset of target genes.
AB - The mechanisms generating epileptic neuronal networks following insults such as
severe seizures are unknown. We have previously shown that interfering with the
function of the neuron-restrictive silencer factor (NRSF/REST), an important
transcription factor that influences neuronal phenotype, attenuated development
of this disorder. In this study, we found that epilepsy-provoking seizures
increased the low NRSF levels in mature hippocampus several fold yet
surprisingly, provoked repression of only a subset (~10%) of potential NRSF
target genes. Accordingly, the repressed gene-set was rescued when NRSF binding
to chromatin was blocked. Unexpectedly, genes selectively repressed by NRSF had
mid-range binding frequencies to the repressor, a property that rendered them
sensitive to moderate fluctuations of NRSF levels. Genes selectively regulated by
NRSF during epileptogenesis coded for ion channels, receptors, and other crucial
contributors to neuronal function. Thus, dynamic, selective regulation of NRSF
target genes may play a role in influencing neuronal properties in pathological
and physiological contexts.
PMID- 25117544
TI - Attention and working memory in elderly: the influence of a distracting
environment.
AB - The present work investigated the effect of a distracting environment in the
performance of attentional and working memory (WM) tasks in elderly participants.
To this end, forty elderly performed two attentional tasks (simple reaction time
and go/no-go tasks), and three WM tasks (arithmetic, memory for digits and
sequences of letters and numbers). Each participant performed the tasks in a
distracting and a non-distracting environment, with an interval of 14-21 days
between sessions. The results revealed better performance in the attentional
tasks when these were done in the non-distracting environment, as compared to
when they were done in the distracting environment. Specifically, participants
provided more accurate responses, fewer false alarms and omissions when
responding in the non-distracting environment than when responding in the
distracting environment. Participants were also faster at providing correct
responses in the go/no-go task when it was performed in the non-distracting
environment. As for the memory tasks, the effect of type of environment was
significant only in the memory for digits in a forward direction task. Our data
suggest the need to consider the potential damaging consequences of distracting
environments when the elderly have to perform tasks that demand their attention.
Specific examples of such situations are presented in the discussion (e.g.,
distracting effect of environment on medical and on psychological evaluations).
PMID- 25117542
TI - Subacute manganese exposure in rats is a neurochemical model of early manganese
toxicity.
AB - Manganese (Mn) is an essential trace element, but excess exposure leads to
accumulation in biological tissues, including the brain. Chronically high Mn
levels in the brain are neurotoxic and can result in a progressive, irreversible
neurological disorder known as manganism. Manganism has signs and symptoms
similar to, but distinguishable from idiopathic Parkinson's disease, which
include both psychological and motor disturbances. Evidence suggests that Mn
exposure impacts neurotransmitter levels in the brain. However, it remains
unclear if subacute, low-level Mn exposure resulted in alterations in
neurotransmitter systems with concomitant behavioral deficits. The current study
used high performance liquid chromatography to quantify neurotransmitter levels
in rat striatum (STR), substantia nigra (SN), and hippocampus (HP). Subacute Mn
exposure via i.p. injection of 15mg Mn/kg as MnCl2 caused significantly increased
dopamine (DA) levels in the STR. The enhancement was accompanied by significantly
elevated levels of the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and
homovanillic acid (HVA), in the STR. In addition, levels of HVA were
significantly increased in the SN and HP. These data indicate that subacute, low
level Mn exposure disrupts multiple neurotransmitter systems in the rat brain
which may be responsible, in part, for observed locomotor deficits.
PMID- 25117545
TI - fadD deletion and fadL overexpression in Escherichia coli increase hydroxy long
chain fatty acid productivity.
AB - A major problem of long-chain fatty acid (LCFA) hydroxylation using Escherichia
coli is that FadD (long-chain fatty acyl-CoA synthetase), which is necessary for
exogenous LCFA transport, also initiates cellular consumption of LCFA. In this
study, an effective method to prevent the cellular consumption of LCFA without
impairing its transport is proposed. The main idea is that a heterologous enzyme
which consumes LCFA can replace FadD in LCFA transport. For the model
heterologous enzyme, CYP153A from Marinobacter aquaeolei, which converts palmitic
acid into omega-hydroxy palmitic acid, was expressed in E. coli. When fadD was
deleted from an E. coli strain, CYP153A indeed maintained the ability to
transport LCFA. A disadvantage of fadD deletion mutant is the fact that FadD
deficiency downregulates the transcription of fadL (outer membrane LCFA
transporter) via FadR (fatty acid metabolism regulator protein), was solved by
fadL overexpression from a plasmid. In addition, the overexpression of fadL was
able to offset catabolite repression on fadL, allowing glucose to be used as the
primary carbon source. In conclusion, the strain with fadD deletion and fadL
overexpression showed 5.5-fold increase in productivity compared to the wild-type
strain, converting 2.6 g/L (10.0 mM) of palmitic acid into 2.4 g/L (8.8 mM) of
omega-hydroxy palmitic acid in a shake flask. This simple genetic manipulation
can be applied to any LCFA hydroxylation using E. coli.
PMID- 25117546
TI - Facile synthesis of oxidic PEG-modified magnetic polydopamine nanospheres for
Candida rugosa lipase immobilization.
AB - A versatile method for the design of polydopamine-coated magnetic material with a
brush-like structure used for Candida Rugosa lipase (CRL) immobilization was
reported in this work. First, polydopamine (PDA) was coated on the surface of
Fe3O4 nanospheres (Fe3O4 NPs) with a controllable thickness via dip coating
process, and CRL can be immobilized on it directly via covalent bonding.
Subsequently, PDA-functionalized Fe3O4 NPs were modified with dialdehyde
polyethylene glycol (PEG) to obtain the aldehyde groups, and the brush-like
structure of the magnetic supports was formed. After being characterized with
various methods, it was verified that the prepared magnetic NPs possessed good
monodispersity and displayed high saturation magnetization after modification.
Meanwhile, the CRL was immobilized on it covalently, and the enzyme activities
such as activity, stability, and reusability were investigated. Significantly,
the versatility of polydopamine-inspired chemistry combined with the unique
biological nature and tunability with dialdehyde PEG could evoke the efficiency
of the CRL, making this a promising coating technique for various bio
applications.
PMID- 25117547
TI - A recombinant porcine circovirus type 2 expressing the VP1 epitope of the type O
foot-and-mouth disease virus is infectious and induce both PCV2 and VP1 epitope
antibodies.
AB - Porcine circovirus type 2 (PCV2) is the etiological agent of postweaning
multisystemic wasting syndrome, a disease that causes huge economic damage in
swine industry. A recombinant PCV2 expressing the neutralizing VP1 epitope (aa
141-160) of the foot-and-mouth disease virus (FMDV) was rescued using an
infectious cloning technique. The PCV2 antigen and FMDV-VP1 antigenic epitope of
the cloned strain recPCV2-CL-VP1 were confirmed by an immunoperoxidase monolayer
assay (IPMA) and a capture enzyme-linked immunosorbent assay (ELISA). The
morphological features of the recPCV2-CL-VP1 were not discernibly different from
those of its parental strain (PCV2-CL). However, the recombinant virus could be
differentiated from its parental virus by PCR and capture ELISA. The recPCV2-CL
VP1 was demonstrated to replicate stably in PK-15 cells through ten passages. An
infection experiment using BALB/c mice showed that both recPCV2-CL-VP1 and PCV2
CL could replicate in the mice, cause various pathological changes, and induce a
high level of anti-Cap antibodies. The recombinant virus emulsified with Freund's
adjuvant was used to immunize BALB/c mice and induced antibodies against the FMDV
VP1 epitope. Hence, the recombinant PCV2 strain, which expressed the neutralizing
FMDV-VP1 epitope, provides a valuable platform to develop novel genetic vaccines.
PMID- 25117548
TI - Development of droplet digital PCR assays for methanogenic taxa and examination
of methanogen communities in full-scale anaerobic digesters.
AB - Droplet digital PCR (ddPCR) is a new DNA quantification platform without an
external DNA calibrator. This study examined methanogen communities in four full
scale anaerobic digesters treating municipal sewage sludge, using ddPCR with
taxon-specific primer/TaqMan probe sets (5 orders, 11 families, and 13 genera),
many of which were developed in this study. Total methanogen abundance was
positively correlated with hydraulic retention time (HRT) and temperature (p <
0.05), though the effect of HRT was stronger (r = 0.864 vs. 0.682, respectively).
Moreover, total abundance was strongly correlated with biogas production rate (r
= 0.896). HRT was positively correlated with seven methanogenic taxa, while
temperature was positively or negatively correlated with 13 taxa (p < 0.05). For
instance, the predominant genera Methanosaeta and Methanosarcina were negatively
and positively associated, respectively, with temperature only (p < 0.05).
Redundancy analysis and principal component analysis using the absolute-abundance
dataset indicated that only temperature explained the variability in the
methanogen communities at all classification levels. Therefore, HRT was the most
important operational factor to influence net methanogen abundance and activity,
while temperature governed the composition of the methanogen community. ddPCR
enabled absolute quantification of methanogens without the external DNA standards
and linked methanogen communities and operational factors, suggesting that it is
a promising tool for analyzing the microbial ecology of anaerobic digestion.
PMID- 25117549
TI - Evaluation of the prebiotic potential of arabinoxylans from brewer's spent grain.
AB - Arabinoxylans (AX) consumption has been related to the treatment and prevention
of cardiovascular diseases, type II diabetes, colorectal cancer and obesity. The
beneficial health effects are conferred through gut microbiota modulation, and
therefore, they have been proposed as potential slowly fermentable prebiotic
candidates. As the mechanisms are not yet well understood, the prebiotic
potential of AX from brewer's spent grain (BSG) has been investigated. Two types
of AX from BSG (AX1 and AX2) of different length and branching averages were
fermented with human faecal inocula and compared to fermented cultures containing
a commercial prebiotic (fructooligosaccharide (FOS)) and cultures with no added
carbohydrate (control). Results demonstrated that the AX were extensively
metabolised after 48 h of fermentation. The pH decreased along fermentation and
the lowest value was achieved in AX1 cultures. The production of short chain
fatty acids (SCFA) was higher in AX cultures than in cultures containing FOS and
controls, with AX1 presenting the highest concentrations. The stimulatory effect
of beneficial bacteria was higher in AX cultures, and AX2 presented the highest
positive effect. Prebiotic potential of AX from BSG was confirmed by the
production of SCFA and the modulation of gut microbiota, especially by the high
increase in bifidobacteria populations.
PMID- 25117550
TI - Polyethylenimine carbon nanotube fiber electrodes for enhanced detection of
neurotransmitters.
AB - Carbon nanotube (CNT)-based microelectrodes have been investigated as
alternatives to carbon-fiber microelectrodes for the detection of
neurotransmitters because they are sensitive, exhibit fast electron transfer
kinetics, and are more resistant to surface fouling. Wet spinning CNTs into
fibers using a coagulating polymer produces a thin, uniform fiber that can be
fabricated into an electrode. CNT fibers formed in poly(vinyl alcohol) (PVA) have
been used as microelectrodes to detect dopamine, serotonin, and hydrogen
peroxide. In this study, we characterize microelectrodes with CNT fibers made in
polyethylenimine (PEI), which have much higher conductivity than PVA-CNT fibers.
PEI-CNT fibers have lower overpotentials and higher sensitivities than PVA-CNT
fiber microelectrodes, with a limit of detection of 5 nM for dopamine. The
currents for dopamine were adsorption controlled at PEI-CNT fiber
microelectrodes, independent of scan repetition frequency, and stable for over 10
h. PEI-CNT fiber microelectrodes were resistant to surface fouling by serotonin
and the metabolite interferant 5-hydroxyindoleacetic acid (5-HIAA). No change in
sensitivity was observed for detection of serotonin after 30 flow injection
experiments or after 2 h in 5-HIAA for PEI-CNT electrodes. The antifouling
properties were maintained in brain slices when serotonin was exogenously applied
multiple times or after bathing the slice in 5-HIAA. Thus, PEI-CNT fiber
electrodes could be useful for the in vivo monitoring of neurochemicals.
PMID- 25117553
TI - Linear and circular dichroism in porphyrin J-aggregates probed by polarization
modulated scanning near-field optical microscopy.
AB - Polarization modulated scanning near-field optical microscopy (PM-SNOM) is
effective in detecting circular and linear dichroism with sub-wavelength
resolution. PM-SNOM investigation of the chiroptical properties of single ribbon
like nanosized J-aggregates formed by acid induced aggregation of tris-(4
sulfonatophenyl)phenylporphyrin is reported. Linear dichroism maps give evidence
of well-organized chromophores packed in linear arrays within the structure of
the nanoribbons. Circular dichroism maps indicate that the molecules forming the
nanoribbon have an inherently chiral structure at the local scale.
PMID- 25117552
TI - Visualization and unsupervised predictive clustering of high-dimensional
multimodal neuroimaging data.
AB - BACKGROUND: Neuroimaging machine learning studies have largely utilized
supervised algorithms - meaning they require both neuroimaging scan data and
corresponding target variables (e.g. healthy vs. diseased) to be successfully
'trained' for a prediction task. Noticeably, this approach may not be optimal or
possible when the global structure of the data is not well known and the
researcher does not have an a priori model to fit the data. NEW METHOD: We set
out to investigate the utility of an unsupervised machine learning technique; t
distributed stochastic neighbour embedding (t-SNE) in identifying 'unseen' sample
population patterns that may exist in high-dimensional neuroimaging data.
Multimodal neuroimaging scans from 92 healthy subjects were pre-processed using
atlas-based methods, integrated and input into the t-SNE algorithm. Patterns and
clusters discovered by the algorithm were visualized using a 2D scatter plot and
further analyzed using the K-means clustering algorithm. COMPARISON WITH EXISTING
METHODS: t-SNE was evaluated against classical principal component analysis.
CONCLUSION: Remarkably, based on unlabelled multimodal scan data, t-SNE separated
study subjects into two very distinct clusters which corresponded to subjects'
gender labels (cluster silhouette index value=0.79). The resulting clusters were
used to develop an unsupervised minimum distance clustering model which
identified 93.5% of subjects' gender. Notably, from a neuropsychiatric
perspective this method may allow discovery of data-driven disease phenotypes or
sub-types of treatment responders.
PMID- 25117551
TI - Reference gene selection for quantitative real-time PCR normalization in
Reaumuria soongorica.
AB - Despite its superiority for evaluating gene expression, real-time quantitative
polymerase chain reaction (qPCR) results can be significantly biased by the use
of inappropriate reference genes under different experimental conditions.
Reaumuria soongorica is a dominant species of desert ecosystems in arid central
Asia. Given the increasing interest in ecological engineering and potential
genetic resources for arid agronomy, it is important to analyze gene function.
However, systematic evaluation of stable reference genes should be performed
prior to such analyses. In this study, the stabilities of 10 candidate reference
genes were analyzed under 4 kinds of abiotic stresses (drought, salt, dark, and
heat) within 4 accessions (HG010, HG020, XGG030, and XGG040) from 2 different
habitats using 3 algorithms (geNorm, NormFinder, and BestKeeper). After
validation of the ribulose-1,5-bisphosphate carboxylase/oxygenase large unite
(rbcL) expression pattern, our data suggested that histone H2A (H2A) and
eukaryotic initiation factor 4A-2 (EIF4A2) were the most stable reference genes,
cyclophilin (CYCL) was moderate, and elongation factor 1alpha (EF1alpha) was the
worst choice. This first systematic analysis for stably expressed genes will
facilitate future functional analyses and deep mining of genetic resources in R.
soongorica and other species of the Reaumuria genus.
PMID- 25117554
TI - Linear signal hyperintensity adjacent to the subchondral bone plate at the knee
on T2-weighted fat-saturated sequences: imaging aspects and association with
structural lesions.
AB - OBJECTIVE: To describe the association between linear T2 signal abnormalities in
the subchondral bone and structural knee lesions. MATERIALS AND METHODS: MR
studies of patients referred for the evaluation of knee pain were retrospectively
evaluated and 133 of these patients presented bone marrow edema pattern (BMEP)
(study group) and while 61 did not (control group). The presence of linear
anomalies of the subchondral bone on T2-weighted fat-saturated sequences was
evaluated. The findings were correlated to the presence of structural knee
lesions and to the duration of the patient's symptoms. Histologic analysis of a
cadaveric specimen was used for anatomic correlation. RESULTS: Linear T2
hyperintensities at the subchondral bone were present in 41% of patients with
BMEP. None of the patients in the control group presented this sign. When a
subchondral linear hyperintensity was present, the prevalence of radial or root
tears was high and that of horizontal tears was low (71.4 and 4.8%,
respectively). Sixty-nine percent of the patients with a subchondral
insufficiency fracture presented a subchondral linear hyperintensity. It was
significantly more prevalent in patients with acute or sub-acute symptoms (p <
0.0001). CONCLUSIONS: The studied linear T2 hyperintensity is located at the
subchondral spongiosa and can be secondary to local or distant joint injuries.
Its presence should evoke acute and sub-acute knee injuries. This sign is closely
related to subchondral insufficiency fractures and meniscal tears with a
compromise in meniscal function.
PMID- 25117555
TI - The scapular glenopolar angle: standard values and side differences.
AB - OBJECTIVE: The aim of this study is to determine normal glenopolar angle (GPA)
values on bone specimens of the scapula and compare them with various
radiological views and CT examination. MATERIALS AND METHODS: GPA values were
measured on 100 mature, dry, non-paired scapulae, 20 pairs of dry scapulae, 50 AP
radiographs of the shoulder, 50 Neer I views, 50 AP chest radiographs and 20 3D
CT reconstructions of the scapula. RESULTS: Measurements made on bone specimens
of the scapula showed an average GPA value of 42.3 degrees ; the mean absolute
side-to-side difference was on average 1.6 degrees . The average GPA measured on
50 AP shoulder radiographs was 35.9 degrees , on Neer I views 40.6 degrees and
AP chest radiographs 37.1 degrees , with the mean absolute side-to-side
difference on average 4.9 degrees ; on 3D CT the average GPA was 43.0 degrees
and the mean absolute side-to-side difference on average 1.4 degrees .
CONCLUSION: GPA values depend on the method of measurement used. Measurements
made on 3D CT reconstructions and Neer I views showed almost the same values as
those measured on bone specimens. The values measured on AP shoulder views and AP
chest radiographs were statistically significantly lower. Side-to-side
variability (right and left) measured on 3D CT reconstructions was insignificant,
and the obtained values corresponded to the values from bone specimens.
Therefore, the best method to measure the GPA is a 3D CT reconstruction and an
exact Neer I projection.
PMID- 25117557
TI - Health-related quality of life among online university students.
AB - BACKGROUND AND OBJECTIVES: Online university students are a growing population
whose health has received minimal attention. The purpose of this cross-sectional
Internet survey was to identify risk factors for the health status among online
university students. METHODS: This online survey collected data from 301 online
university students through a large, US-based participant pool and LinkedIn.
Health status was measured using 3 elements of health-related quality of life
(HRQOL): self-rated overall health (SRH), unhealthy days, and recent activity
limitation days. All 3 measures were dichotomized. RESULTS: The odds of poor SRH
were higher for people who reported a body mass index in the overweight and obese
categories (odds ratio [OR] = 2.99, P < .05) and for those who reported being
smokers (OR = 2.52, P = .03). The odds of frequent unhealthy days were lower for
those who made more than $35 000 compared with those who reported making less (OR
= 0.50, P = .03) and those who exercised 4 or more times a week compared with
those who exercised less (OR = 0.28, P < .05). The odds of frequent activity
limitation were lower for those who reported an income of more than $35 000 (OR =
0.29, P = .04) and higher for persons who reported belonging to "other" race (OR
= 14.75, P = .00). CONCLUSIONS: Universities might fruitfully target health
promotion programs for online students who are low income, in disadvantaged
racial groups, who are overweight, smoke, and who do not exercise.
PMID- 25117558
TI - The limits of traditional approaches to informed consent for genomic medicine.
AB - This paper argues that it will be important for new genomic technologies to
recognize the limits of traditional approaches to informed consent, so that other
regarding implications of genomic information can be properly contextualized and
individual rights respected. Respect for individual autonomy will increasingly
require dynamic consideration of the interrelated dimensions of individual and
broader community interests, so that the interests of one do not undermine
fundamental interests of the other. In this, protection of individual rights will
be a complex interplay between individual and community concerns.
PMID- 25117559
TI - Engineering bacterial microcompartment shells: chimeric shell proteins and
chimeric carboxysome shells.
AB - Bacterial microcompartments (BMCs) are self-assembling organelles composed
entirely of protein. Depending on the enzymes they encapsulate, BMCs function in
either inorganic carbon fixation (carboxysomes) or organic carbon utilization
(metabolosomes). The hallmark feature of all BMCs is a selectively permeable
shell formed by multiple paralogous proteins, each proposed to confer specific
flux characteristics. Gene clusters encoding diverse BMCs are distributed broadly
across bacterial phyla, providing a rich variety of building blocks with a
predicted range of permeability properties. In theory, shell permeability can be
engineered by modifying residues flanking the pores (symmetry axes) of hexameric
shell proteins or by combining shell proteins from different types of BMCs into
chimeric shells. We undertook both approaches to altering shell properties using
the carboxysome as a model system. There are two types of carboxysomes, alpha and
beta. In both, the predominant shell protein(s) contain a single copy of the BMC
domain (pfam00936), but they are significantly different in primary structure.
Indeed, phylogenetic analysis shows that the two types of carboxysome shell
proteins are more similar to their counterparts in metabolosomes than to each
other. We solved high resolution crystal structures of the major shell proteins,
CsoS1 and CcmK2, and the presumed minor shell protein CcmK4, representing both
types of cyanobacterial carboxysomes and then tested the interchangeability. The
in vivo study presented here confirms that both engineering pores to mimic those
of other shell proteins and the construction of chimeric shells is feasible.
PMID- 25117556
TI - Profiles of Risk Among HIV-Infected Youth in Clinic Settings.
AB - Despite the rising number of new HIV infections among youth, few tailored
interventions for youth living with HIV (YLH) have been developed and rigorously
tested. Developing tailored interventions necessitates identifying different
profiles of YLH and understanding how risk and protective factors cluster
together. Obtaining this critical information requires accessing a sufficiently
large sample of YLH from diverse geographic settings such as those available
through the Adolescent Trials Network for HIV Interventions (ATN). We recruited a
cross-sectional sample of 1,712 YLH from ATN clinics; participants completed a
survey on psychosocial and health factors. Using latent class analysis on nine
composite variables representing risk factors, we identified five classes
distinguished by substance use, sexual behavior, and pregnancy history and
differing on health outcomes. Findings suggest a need for tailored interventions
addressing multiple risky behaviors of HIV-infected youth and research to clarify
how intervention effectiveness may differ by risk profile.
PMID- 25117560
TI - Nitrogen-enriched, double-shelled carbon/layered double hydroxide hollow
microspheres for excellent electrochemical performance.
AB - A unique, double-shelled, hollow, carbon-based composite with enriched nitrogen
has been prepared through a facile and versatile synthetic strategy. The
hierarchical composite employs the nitrogen-enriched carbon hollow sphere as an
interior shell and intercrossed Ni/Al layered double hydroxide (LDH) nanosheets
as an exterior shell. The obtained N-C@LDH hollow microspheres (HMS) have high
nitrogen enrichment, large specific surface area (337 m(2) g(-1)), and uniform
and open mesoporous structure. Taking advantage of these characteristics, the
composite exhibits obviously superior capacitive behavior, including high
specific capacitance, excellent rate capability and good cycling stability,
compared with nitrogen-free carbon@LDH composite and hollow LDH without carbon
shell. The composite displays high specific capacitance of 1711.51 F g(-1) at a
current density of 1 A g(-1). In particular, the high specific capacitance can be
kept to 997.3 F g(-1) at a high current density of 10 A g(-1), which still
retains 94.97% of the initial specific capacitance after 500 cycles at this high
current density. This N-enriched, hollow carbon/LDH composite can be expected to
be a promising electrode material for electrochemical capacitors due to its high
electrochemical performance.
PMID- 25117561
TI - MDCT diagnosis of gastroduodenal ulcers: key imaging features with endoscopic
correlation.
AB - Although the overall prevalence of peptic ulcer disease (PUD) and related
hospitalizations are decreasing, the initial presentation of complicated PUD on
CT remains common. It, therefore, remains critical for radiologists to recognize
the findings of PUD at CT for initial diagnosis. While the CT findings of
complicated PUD have been previously described in the literature, the CT findings
of uncomplicated PUD have not been well documented. Furthermore, although CT is
certainly not the diagnostic evaluation of choice for patients with suspected
uncomplicated PUD, many patients with PUD will nonetheless present to the
emergency department with unexplained abdominal pain and undergo MDCT evaluation
as the initial diagnostic test. Therefore, recognizing the MDCT findings of
uncomplicated PUD can help appropriately direct patient management, and help
prevent the development of complications. To facilitate improved recognition of
PUD on abdominal CT, we present an overview of the CT findings of both
uncomplicated and complicated PUD, as well as several diagnostic pitfalls which
can result in misdiagnosis from peptic ulcer mimics.
PMID- 25117562
TI - Diffusion-weighted imaging of the liver: comparison of image quality between
monopolar and bipolar acquisition schemes at 3T.
AB - PURPOSE: To compare image quality of monopolar and bipolar diffusion-weighted
imaging (DWI) sequences of the liver at 3T. METHODS: 32 healthy volunteers (mean
27 +/- 8 years; 27 M/5F) and 11 patients (mean age 58 +/- 14 years; 8 M/3F)
underwent liver MRI using a 3T system incorporating 2-channel parallel
transmission for B1-shimming and reduced B1-inhomogeneity. Scans included free
breathing DWI sequences (b-value 0, 400, 800 s/mm(2)) acquired using both
monopolar and bipolar techniques. Estimated signal-to-noise ratio (eSNR),
apparent diffusion coefficient (ADC), and measures of subjective image quality on
b-800 images, scored on a 1-5 scale by two independent radiologists, were
compared between sequences. RESULTS: Monopolar sequence demonstrated
significantly higher eSNR (volunteers: 12.7 +/- 4.0 vs. 11.3 +/- 3.5, patients:
11.4 +/- 4.0 vs. 10.2 +/- 3.3; p <= 0.013) compared with the bipolar sequence.
Monopolar sequence also achieved significantly higher scores for reader 1 in
volunteers and patients in terms of clarity of right lobe edge, clarity of intra
hepatic vessels, conspicuity of the left lobe, and overall diagnostic quality (p
<= 0.031), as well as significantly higher scores for reader 2 in volunteers in
terms of clarity of intra-hepatic vessels, conspicuity of the left lobe, and
overall diagnostic quality (p <= 0.035). Respiratory motion artifact was not
significantly different between sequences in patients or volunteers for either
reader (p >= 0.191). Hepatic ADC was significantly lower using monopolar
technique only in volunteers (1.28 +/- 0.12 vs. 1.43 +/- 0.15, p < 0.001).
CONCLUSION: In comparison with past studies performed at 1.5T, when using a
modern 3T system, we observed improved image quality of liver DWI using a
monopolar, rather than a bipolar, acquisition scheme, largely attributed to
higher eSNR.
PMID- 25117563
TI - Multimodality imaging of penile cancer: what radiologists need to know.
AB - The purpose of this article is to provide a comprehensive update on the role of
imaging in the diagnosis and management of penile cancer. Imaging plays a major
role in the initial assessment, treatment planning, and follow-up of patients
with penile carcinoma. MRI helps in assessing the T staging of the primary and in
detecting local recurrence. PET/CT and CT are useful for detecting regional nodal
and distant metastases.
PMID- 25117564
TI - Maternal smoking during pregnancy and adverse outcomes in offspring: genetic and
environmental sources of covariance.
AB - Maternal smoking during pregnancy (SDP) has been associated with several
psychiatric outcomes in the offspring; studies have questioned whether the
associations are causal, however. We analyzed all children born in Sweden between
1983 and 2009 to investigate the effect of SDP on multiple indicators of adverse
outcomes in three areas: pregnancy outcomes (birth weight, preterm birth and
being born small for gestational age), long-term cognitive abilities (low
academic achievement and general cognitive ability) and externalizing behaviors
(criminal conviction, violent criminal conviction and drug misuse). SDP was
associated with all outcomes. Within-family analyses of the pregnancy outcomes
were consistent with a causal interpretation as the associations persisted when
siblings discordant for SDP were compared. For the cognitive and externalizing
outcomes, the results were not consistent with causal effects; when comparing
differentially exposed siblings none of the associations remained significant. In
quantitative genetic models genetic factors explained the majority of the
associations between SDP and cognitive and externalizing outcomes. The results
suggest that the associations between SDP in mothers and cognition and
externalizing behaviors in their offspring is primarily due to genetic effects
that influence the behaviors in both generations.
PMID- 25117566
TI - Secretoglobin 3A2 attenuates lipopolysaccharide-induced inflammation through
inhibition of ERK and JNK pathways in bronchial epithelial cells.
AB - Secretoglobin (SCGB) 3A2, previously known as uteroglobin-related protein 1, is a
secreted protein highly expressed in the epithelial cells of the airways. It has
been demonstrated that SCGB3A2 is involved in allergic airway inflammation such
as bronchial asthma. However, the role of SCGB3A2 in lipopolysaccharide (LPS)
induced airway inflammation has yet to be reported. The goal of this study was
therefore to clarify the role of SCGB3A2 in LPS-induced airway inflammation. We
stimulated BEAS-2B, human bronchial epithelial cells, with LPS and analyzed
messenger RNA (mRNA) expression of tumor necrosis factor (TNF)-alpha and CXCL8
with or without pre-incubation of SCGB3A2. The mRNA expression of TNF-alpha and
CXCL8 was clearly upregulated 3 h after LPS stimulation, and pre-incubation of
SCGB3A2 significantly inhibited the upregulation of the mRNA expression. The pre
incubation of SCGB3A2 also inhibited LPS-induced phosphorylation of extracellular
signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not p38
mitogen-activated protein kinase in BEAS-2B cells. Furthermore, PD98059, a
specific inhibitor for ERK, as well as SP600125, a specific inhibitor for JNK,
inhibited LPS-induced mRNA upregulation of inflammatory mediators. These results
demonstrate the novel biological activity of SCGB3A2, which is that it attenuates
LPS-induced inflammation in bronchial epithelial cells through inhibition of ERK
and JNK activation.
PMID- 25117565
TI - Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic
from non-ischemic end stage heart failure.
AB - The molecular differences between ischemic (IF) and non-ischemic (NIF) heart
failure are poorly defined. A better understanding of the molecular differences
between these two heart failure etiologies may lead to the development of more
effective heart failure therapeutics. In this study extensive proteomic and
phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or
NIF were assembled and compared. Proteins extracted from left ventricular
sections were proteolyzed and phosphopeptides were enriched using titanium
dioxide resin. Gel- and label-free nanoscale capillary liquid chromatography
coupled to high resolution accuracy mass tandem mass spectrometry allowed for the
quantification of 4,436 peptides (corresponding to 450 proteins) and 823
phosphopeptides (corresponding to 400 proteins) from the unenriched and phospho
enriched fractions, respectively. Protein abundance did not distinguish NIF from
IF. In contrast, 37 peptides (corresponding to 26 proteins) exhibited a >= 2-fold
alteration in phosphorylation state (p<0.05) when comparing IF and NIF. The
degree of protein phosphorylation at these 37 sites was specifically dependent
upon the heart failure etiology examined. Proteins exhibiting phosphorylation
alterations were grouped into functional categories: transcriptional
activation/RNA processing; cytoskeleton structure/function; molecular chaperones;
cell adhesion/signaling; apoptosis; and energetic/metabolism. Phosphoproteomic
analysis demonstrated profound post-translational differences in proteins that
are involved in multiple cellular processes between different heart failure
phenotypes. Understanding the roles these phosphorylation alterations play in the
development of NIF and IF has the potential to generate etiology-specific heart
failure therapeutics, which could be more effective than current therapeutics in
addressing the growing concern of heart failure.
PMID- 25117567
TI - Naringin attenuates the development of carrageenan-induced acute lung
inflammation through inhibition of NF-kappab, STAT3 and pro-inflammatory
mediators and enhancement of IkappaBalpha and anti-inflammatory cytokines.
AB - Naringin has been reported to possess diverse pharmacological properties,
including anti-arthritic and anti-inflammatory activities. The aim of the present
study was to determine the potential anti-inflammatory effect of naringin in a
mouse model of carrageenan-induced pleurisy. A single dose of naringin (40 and 80
mg/kg) was administered per oral (p.o.) 1 h before carrageenan (Cg)
administration. Pro- and anti-inflammatory cytokines were analysed in pleural
fluid. We also assessed the effects of naringin on the expression levels of iNOS,
inducible cyclooxygenase isoform (COX-2), ICAM-1, MIP-2, PGE2, STAT3, TGF-beta1,
nuclear factor kappa B (NF-kappaB) and inhibitor of kappa B (IkappaBalpha) in
lung tissue. The histological examinations revealed anti-inflammatory effect of
naringin while Cg group deteriorated. Naringin downregulated Th1 and upregulated
Th2 cytokines. Western blot analyses revealed increased protein expression of NF
kappaB, STAT3 and COX-2 and decreased IkappaBalpha in response to Cg treatment,
which were reversed by the treatment with naringin. In the Cg group, mRNA
expression levels of pro-inflammatory mediators upregulated and anti-inflammatory
mediators downregulated. Naringin reversed these actions.
PMID- 25117568
TI - Silymarin attenuates airway inflammation induced by cigarette smoke in mice.
AB - Cigarette smoke (CS), which increases inflammation and oxidative stress, is a
major risk factor for the development of COPD. In this study, we investigated the
effects of silymarin, a polyphenolic flavonoid isolated from the seeds and fruits
of milk thistle, on CS-induced airway inflammation and oxidative stress in mice
and the possible mechanisms. BALB/c mice were exposed to CS for 2 h twice daily,
6 days per week for 4 weeks. Silymarin (25, 50 mg/kg.day) was administered
intraperitoneally 1 h before CS exposure. Bronchoalveolar lavage fluid (BALF) was
acquired for cell counting and the detection of pro-inflammatory cytokine levels.
Lung tissue was collected for histological examination, myeloperoxidase (MPO)
activity assay, superoxide dismutase (SOD) activities, and malondialdehyde (MDA)
levels. The phosphorylation of ERK and p38 was evaluated by Western blotting.
Pretreatment with silymarin significantly attenuated CS-induced thickening of the
airway epithelium, peribronchial inflammatory cell infiltration, and lumen
obstruction. The numbers of total cells, macrophages, and neutrophils, along with
the MPO activity (a marker of neutrophil accumulation) in BALF, were remarkably
decreased by silymarin in CS-exposed mice (all p<0.05). In addition, silymarin
pretreatment dampened the secretion of TNF-alpha, IL-1beta, and IL-8 in BALF.
High-dose silymarin (50 mg/kg.day) administration also prevented CS-induced
elevation in MDA levels and decrease in SOD activities (p<0.05). Furthermore, the
CS-induced phosphorylation of ERK and p38 was also attenuated by silymarin
(p<0.05). These results suggest that silymarin attenuated inflammation and
oxidative stress induced by cigarette smoke. The anti-inflammatory effect might
partly act through the mitogen-activated protein kinases (MAPK) pathway.
PMID- 25117570
TI - Liver status in congenital, untreated, isolated GH deficiency.
AB - Nonalcoholic fatty liver disease (NAFLD) is known to be associated with insulin
resistance, atherosclerosis, and low serum IGF1 levels. We have described a large
cohort of patients with isolated GH deficiency (IGHD) due to the c.57+1G->A
mutation in the GHRH receptor gene. These subjects have increased insulin
sensitivity (IS), delayed atherosclerosis, and normal longevity. We hypothesized
that, despite visceral obesity, NAFLD would be absent or mild due to the
increased IS. To assess the prevalence and severity of NAFLD in adult subjects
with lifetime, congenital, untreated IGHD, we studied 22 IGHD adults and 25
controls (COs) matched for age and sex. NAFLD was assessed by a comprehensive
liver function panel, and ultrasonographic pattern (hyperechogenic pattern, HP)
coded as follows: 0, absent; 1, mild; 2, moderate; and 3, severe. Compared with
COs, IGHD individual had lower serum IGF1 (P<0.0001), higher total cholesterol
(P=0.027), lower prothrombin time (P=0.017), and similar activated partial
thromboplastin time and fibrinogen values. Alanine transaminase (ALT) values were
similar in the two groups, but aspartate transaminase was higher in IGHD
(P=0.013). However, more IGHD subjects (7/22) than COs (3/23) had ALT above the
upper limit of normal (P=0.044). The prevalence of NAFLD was higher in IGHD than
COs (61 vs 29%, P=0.032), and the HP score was higher in IGHD than COs (P=0.041),
but severe NAFLD was not observed in any IGHD (or CO) individual. Liver HP score
is increased in lifetime, untreated, congenital IGHD, but the increase in
transaminases is mild, suggesting a lack of advanced forms of NAFLD.
PMID- 25117569
TI - Surface engineering of graphene-based nanomaterials for biomedical applications.
AB - Graphene-based nanomaterials have attracted tremendous interest over the past
decade due to their unique electronic, optical, mechanical, and chemical
properties. However, the biomedical applications of these intriguing
nanomaterials are still limited due to their suboptimal
solubility/biocompatibility, potential toxicity, and difficulties in achieving
active tumor targeting, just to name a few. In this Topical Review, we will
discuss in detail the important role of surface engineering (i.e.,
bioconjugation) in improving the in vitro/in vivo stability and enriching the
functionality of graphene-based nanomaterials, which can enable
single/multimodality imaging (e.g., optical imaging, positron emission
tomography, magnetic resonance imaging) and therapy (e.g., photothermal therapy,
photodynamic therapy, and drug/gene delivery) of cancer. Current challenges and
future research directions are also discussed and we believe that graphene-based
nanomaterials are attractive nanoplatforms for a broad array of future biomedical
applications.
PMID- 25117572
TI - Hot carriers in epitaxial graphene sheets with and without hydrogen
intercalation: role of substrate coupling.
AB - The development of graphene electronic devices produced by industry relies on
efficient control of heat transfer from the graphene sheet to its environment. In
nanoscale devices, heat is one of the major obstacles to the operation of such
devices at high frequencies. Here we have studied the transport of hot carriers
in epitaxial graphene sheets on 6H-SiC (0001) substrates with and without
hydrogen intercalation by driving the device into the non-equilibrium regime.
Interestingly, we have demonstrated that the energy relaxation time of the device
without hydrogen intercalation is two orders of magnitude shorter than that with
hydrogen intercalation, suggesting application of epitaxial graphene in high
frequency devices which require outstanding heat exchange with an outside cooling
source.
PMID- 25117571
TI - Circulating IGF1 and IGF2 and SNP genotypes in men and pregnant and non-pregnant
women.
AB - Circulating IGFs are important regulators of prenatal and postnatal growth, and
of metabolism and pregnancy, and change with sex, age and pregnancy. Single
nucleotide polymorphisms (SNPs) in genes coding for these hormones associate with
circulating abundance of IGF1 and IGF2 in non-pregnant adults and children, but
whether this occurs in pregnancy is unknown. We therefore investigated
associations of plasma IGF1 and IGF2 with age and genotype at candidate SNPs
previously associated with circulating IGF1, IGF2 or methylation of the INS-IGF2
H19 locus in men (n=134), non-pregnant women (n=74) and women at 15 weeks of
gestation (n=98). Plasma IGF1 concentrations decreased with age (P<0.001) and
plasma IGF1 and IGF2 concentrations were lower in pregnant women than in non
pregnant women or men (each P<0.001). SNP genotypes in the INS-IGF2-H19 locus
were associated with plasma IGF1 (IGF2 rs680, IGF2 rs1004446 and IGF2 rs3741204)
and IGF2 (IGF2 rs1004446, IGF2 rs3741204 and H19 rs217727). In single SNP models,
effects of IGF2 rs680 were similar between groups, with higher plasma IGF1
concentrations in individuals with the GG genotype when compared with GA
(P=0.016), or combined GA and AA genotypes (P=0.003). SNPs in the IGF2 gene
associated with IGF1 or IGF2 were in linkage disequilibrium, hence these
associations could reflect other genotype variations within this region or be due
to changes in INS-IGF2-H19 methylation previously associated with some of these
variants. As IGF1 in early pregnancy promotes placental differentiation and
function, lower IGF1 concentrations in pregnant women carrying IGF2 rs680 A
alleles may affect placental development and/or risk of pregnancy complications.
PMID- 25117573
TI - Interleukin-6 and other inflammatory markers in diagnosis of periprosthetic joint
infection.
AB - PURPOSE: The purpose of this study was to evaluate the diagnostic value of
interleukin-6 (IL-6) and other inflammatory markers including C-reactive protein
(CRP), erythrocyte sedimentation rate (ESR), and white blood cell count (WCC) in
diagnosis of PJI. METHODS: The study group included 40 patients (21 males, 19
females) admitted for surgical intervention after knee or hip arthroplasties.
Patients were subjected to careful history taking, thorough clinical examination
and pre-operative laboratory investigations including serum IL-6, CRP, WCC and
ESR. Peri-implant tissue specimens were subjected to microbiological culture and
histopathological examination. RESULTS: The mean age of patients was 58.4 years
(range, 38-72 years). Intra-operative cultures and histopathological examination
revealed 11 patients had been infected (PJI) and 29 patients were aseptic failure
of prosthesis. Four presumed markers of infection were tested preoperatively:
ESR, CRP, WCC, and IL-6. ESR (p = 0.0001), CRP (p = 0.004), WCC (0.0001), and IL
6 (p = 0.0001) were significantly higher in patients with septic revision than
those with aseptic failure of the prosthesis. Serum IL-6 (>10.4 pg/ml) reportedly
had a sensitivity of 100%, a specificity of 90.9%, a PPV of 79%, a NPV of 100%,
and accuracy of 92.5%. CONCLUSIONS: The present study demonstrated that IL-6 has
been found to be the most accurate laboratory marker for diagnosing PJI when
compared to ESR, CRP, and WCC. IL-6 above 10.4 pg/ml and CRP level above 18 mg/L
will identify all patients with PJI and the combination of CRP + IL-6 is an
excellent screening test to identify all such patients (sensitivity 100%, NPV
100%).
PMID- 25117576
TI - Flicker-Induced Time Dilation Does Not Modulate EEG Correlates of Temporal
Encoding.
AB - In this study, we used EEG to investigate how visual stimulus dynamics (i.e.
flicker) affect the mechanisms of duration perception. Previous studies have
demonstrated that flickering visual stimuli are judged longer than equally long
non-flickering stimuli. We tested whether this effect of flicker on duration
judgments is mediated by changes in temporal encoding during the time interval.
Here, temporal encoding refers to the perception of the unfolding of time
throughout the temporal interval, also termed the "clock stage" in information
processing models of interval timing. We hypothesized that if flicker mediates
duration perception by affecting temporal encoding, then the dilation-effect
should be reflected by neural correlates of temporal encoding. We presented
flickering and steady stimuli in a duration bisection task and found that flicker
dilated perceived duration. The EEG analysis allowed us to isolate a putative
neural correlate of temporal encoding: a modulation of the amplitude of the
contingent negative variation (CNV) by stimuli classified as "long" compared to
physically identical stimuli classified as "short". However, flicker did not
affect the CNV amplitude, suggesting that flicker does not dilate perceived
duration by affecting temporal encoding. Possibly, flicker might affect only
later stages of temporal processing such as interval comparison or decision
making.
PMID- 25117575
TI - Prevalence of femoro-acetabular impingement in international competitive track
and field athletes.
AB - PURPOSE: The aim of our study was to analyse the prevalence of femoro-acetabular
impingement (FAI) in national elite track and field athletes compared to peers
using magnetic resonance imaging (MRI) and clinical examination including
impingement tests. METHODS: A total of 44 participants (22 national elite track
and field athletes and 22 non-athletes) underwent an MRI for radiological
findings associated with FAI, including alpha angle, lateral centre edge angle
(CEA), findings of labral and cartilage lesions. The study group was furthermore
investigated by the hip outcome score (HOS) and a clinical hip examination
including range of motion (ROM) and impingement tests. RESULTS: Concerning the
cam impingement, there was a significant difference measured by mean alpha angle
between the athlete group (52.2 +/- 7.29 degrees ) and the control group (48.1 +/
5.45 degrees , P = 0.004). Eleven athletes showed a cam impingement, while two
probands of the control group had a pincer impingement and one a mixed form (P =
0.0217). There was no statistically significant difference concerning the CEA
upon evaluating pincer impingement. Seven track and field athletes had a positive
impingement test, whereof three had an increased alpha angle >55 degrees . No
participant of the control group showed pathological results in the impingement
test (P = 0.0121). CONCLUSIONS: MRI evidence and clinical examination suggest
that cam impingement is more common in elite athletes in comparison to non
athletes. At a professional level, the intense practice of track and field
athletics is susceptible for FAI.
PMID- 25117574
TI - Evaluation of intervertebral disc regeneration with implantation of bone marrow
mesenchymal stem cells (BMSCs) using quantitative T2 mapping: a study in rabbits.
AB - PURPOSE: The aim of the study was to investigate the curative effects of
transplantation of bone marrow mesenchymal stem cells (BMSCs) on intervertebral
disc regeneration and to investigate the feasibility of the quantitative T2
mapping method for evaluating repair of the nucleus pulposus after implantation
of BMSCs. METHODS: Forty-eight New Zealand white rabbits were used to establish
the lumber disc degenerative model by stabbing the annulus fibrosus and then
randomly divided into four groups, i.e. two weeks afterwards, BMSCs or phosphate
buffered saline (PBS) were transplanted into degenerative discs (BMSCs group and
PBS group), while the operated rabbits without implantation of BMSCs or PBS
served as the sham group and the rabbits without operation were used as the
control group. At weeks two, six and ten after operation, the T2 values and disc
height indices (DHI) were calculated by magnetic resonance imaging (MRI 3.0 T),
and the gene expressions of type II collagen (COL2) and aggrecan (ACAN) in
degenerative discs were evaluated by real-time reverse transcription polymerase
chain reaction (RT-PCR). T2 values for the nucleus pulposus were correlated with
ACAN or COL2 expression by regression analysis. RESULTS: Cell clusters,
disorganised fibres, interlamellar glycosaminoglycan (GAG) matrix and
vascularisation were observed in lumber degenerative discs. BMSCs could be found
to survive in intervertebral discs and differentiate into nucleus pulposus-like
cells expressing COL2 and ACAN. The gene expression of COL2 and ACAN increased
during ten weeks after transplantation as well as the T2 signal intensity and T2
value. The DHI in the BMSCs group decreased more slowly than that in PBS and sham
groups. The T2 value correlated significantly with the gene expression of ACAN
and COL2 in the nucleus pulposus. CONCLUSIONS: Transplantation of BMSCs was able
to promote the regeneration of degenerative discs. Quantitative and non-invasive
T2 mapping could be used to evaluate the regeneration of the nucleus pulposus
with good sensitivity.
PMID- 25117577
TI - Dimensions of oppositional defiant disorder in young children: model comparisons,
gender and longitudinal invariance.
AB - Identifying the latent structure of Oppositional Defiant Disorder (ODD) may have
important clinical and research implications. The present study compared existing
dimensional models of ODD for model fit and examined the metric and scalar
invariance of the best-fitting model. Study participants were a diverse (38.8%
minority, 49.1% boys) community sample of 796 children. Parents completed the
Child Symptom Inventory and the DISC-YC ODD scales at child ages of 4, 5 and 6-7
years. When comparing single-factor (DSM-IV model), two-factor (oppositional
behavior, negative affect), and three-factor models (one with dimensions of
oppositional behavior, negative affect, antagonistic behavior; a second with
dimensions of irritable, hurtful, and headstrong), the two-factor model showed
the best fit. The two-factor model showed configural, metric and scalar
invariance across gender and age. Results suggest that, among existing models,
ODD is best characterized as two separate dimensions, one behavioral and one
affective, which are comparable for both boys and girls in these age groups.
PMID- 25117578
TI - Positive affect in infant siblings of children diagnosed with autism spectrum
disorder.
AB - Research on the expression of positive affect in young children with Autism
Spectrum Disorder (ASD) suggests that differences in this domain emerge late in
the first year or early in the second year. However, many previous studies in
this area employed retrospective research methods and global rating schemes. In
the current study, the expression of positive affect was examined prospectively
at ages 6, 12, and 18 months in three groups: infant siblings with ASD, infant
siblings without ASD, and low-risk comparison infants. Infant siblings were the
younger brothers or sisters of children diagnosed with ASD and, therefore, had a
higher familial risk of ASD. The frequency and duration of smiles were coded from
video excerpts from the Autism Observation Scale for Infants (Bryson,
Zwaigenbaum, McDermott, Rombough, and Brian 2008), a standardized, play-based
assessment of early signs of ASD. Results indicated that at 12 months, infant
siblings with ASD had a lower rate of smiling than the other two groups. At 18
months, infant siblings with ASD continued to display a lower rate of smiling
than infant siblings without ASD, but not comparison infants. Overall, these
results indicate that infant siblings with ASD demonstrate less positive affect
than infant siblings without ASD and low-risk comparison infants at 12 months.
This suggests that reduced smiling may be an informative behavioural risk marker
for ASD by children's first birthdays and may have implications for our
understanding of atypical social development in children with ASD.
PMID- 25117579
TI - Highly efficient graphene-based Cu(In, Ga)Se2 solar cells with large active area.
AB - Two-dimensional graphene has tremendous potential to be used as a transparent
conducting electrode (TCE), owing to its high transparency and conductivity. To
date graphene films have been applied to several kinds of solar cells except the
Cu(In, Ga)Se2 (CIGS) solar cell. In this work, we present a novel TCE structure
consisting of a doped graphene film and a thin layer of poly(methyl methacrylate)
(PMMA) to replace the ZnO:Al (AZO) electrode for CIGS. By optimizing the contact
between graphene and intrinsic ZnO (i-ZnO), a high power conversion efficiency
(PCE) of 13.5% has been achieved, which is among the highest efficiencies of
graphene-based solar cells ever reported and approaching those of AZO-based solar
cells. Besides, the active area of our solar cells reaches 45 mm(2), much larger
than other highly efficient graphene-based solar cells (>10%) reported so far.
Moreover, compared with AZO-based CIGS solar cells, the total reflectance of the
graphene-based CIGS solar cells is decreased and the quantum efficiency of the
graphene-based CIGS is enhanced in the near infrared region (NIR), which strongly
support graphene as a competitive candidate material for the TCE in the CIGS
solar cell. Furthermore, the graphene/PMMA film can protect the solar cell from
moisture, making the graphene-based solar cells much more stable than the AZO
based solar cells.
PMID- 25117581
TI - Reconstruction of the septum with an autogenous double-layered conchal L-strut.
AB - BACKGROUND: One of the most important preconditions for a straight nose is a
straight and stable cartilaginous L-shaped frame with sufficient support for the
nasal tip and the cartilaginous dorsum. Where the structure of the septal
cartilage is destroyed, a sufficient L-strut must be reconstructed. This article
presents a technique for reconstruction of an autogenous L-strut using double
layered conchal cartilages. METHODS: A retrospective review was conducted with a
subsequent follow-up evaluation 10.5-22 months later. The conchal L-strut was
used for 26 patients to reconstruct a new septal frame. The full details of the
planning process, L-frame construction, and technical data are described together
with two typical cases. RESULTS: In all 26 cases, the authors were able to
reconstruct a sufficient neoseptum. In 25 cases, the neoseptum remained straight.
Only in one case did the anterior border deviate immediately after the operation.
No slippage from the nasal spine was found. The anchoring to the nasal bones and
the upper lateral cartilages was stable. However, one asymmetric columella base
was found, caused by an asymmetric support to the footplates by the transplant.
The osteocartilagenous vault was successfully reconstructed in all the patients.
Of the 26 patients, 25 described a marked improvement in their nasal breathing.
CONCLUSION: The reported technique enables the surgeon to reconstruct the
complete cartilagenous L-frame with both conchal cartilages. For certain cases,
this technique of autogenous reconstruction of the nasal septum could be a
valuable alternative to reconstruction with rib cartilage.
PMID- 25117582
TI - Silver confined within zeolite EMT nanoparticles: preparation and antibacterial
properties.
AB - The preparation of pure zeolite nanocrystals (EMT-type framework) and their
silver ion-exchanged (Ag(+)-EMT) and reduced silver (Ag(0)-EMT) forms is
reported. The template-free zeolite nanocrystals are stabilized in water
suspensions and used directly for silver ion-exchange and subsequent chemical
reduction under microwave irradiation. The high porosity, low Si/Al ratio, high
concentration of sodium and ultrasmall crystal size of the EMT-type zeolite
permitted the introduction of a high amount of silver using short ion-exchange
times in the range of 2-6 h. The killing efficacy of pure EMT, Ag(+)-EMT and
Ag(0)-EMT against Escherichia coli was studied semi-quantitatively. The
antibacterial activity increased with increasing Ag content for both types of
samples (Ag(+)-EMT and Ag(0)-EMT). The Ag(0)-EMT samples show slightly enhanced
antimicrobial efficacy compared to that of Ag(+)-EMT, however, the differences
are not substantial and the preparation of Ag nanoparticles is not viable
considering the complexity of preparation steps.
PMID- 25117580
TI - TORC1 regulates Pah1 phosphatidate phosphatase activity via the Nem1/Spo7 protein
phosphatase complex.
AB - The evolutionarily conserved target of rapamycin complex 1 (TORC1) controls
growth-related processes such as protein, nucleotide, and lipid metabolism in
response to growth hormones, energy/ATP levels, and amino acids. Its deregulation
is associated with cancer, type 2 diabetes, and obesity. Among other substrates,
mammalian TORC1 directly phosphorylates and inhibits the phosphatidate
phosphatase lipin-1, a central enzyme in lipid metabolism that provides
diacylglycerol for the synthesis of membrane phospholipids and/or triacylglycerol
as neutral lipid reserve. Here, we show that yeast TORC1 inhibits the function of
the respective lipin, Pah1, to prevent the accumulation of triacylglycerol.
Surprisingly, TORC1 regulates Pah1 in part indirectly by controlling the
phosphorylation status of Nem1 within the Pah1-activating, heterodimeric Nem1
Spo7 protein phosphatase module. Our results delineate a hitherto unknown TORC1
effector branch that controls lipin function in yeast, which, given the recent
discovery of Nem1-Spo7 orthologous proteins in humans, may be conserved.
PMID- 25117583
TI - Revisiting cognitive and adaptive functioning in children and adolescents with
autism spectrum disorder.
AB - Profiles of performance on the Stanford Binet Intelligence Scales (SB5) and
Vineland Adaptive Behavior Scales (VABS) were examined in 73 children and
adolescents with autism spectrum disorder. SB5 cognitive profiles were observed
to be similar between participants with and without early language delay, but
different between participants with and without intellectual disability. With few
exceptions, the distribution and cognitive profiles of participants with specific
nonverbal IQ-verbal IQ and abbreviated IQ-full scale IQ discrepancy patterns
paralleled previous reports. A cognitive functioning advantage over adaptive
functioning was observed to be strongest in participants without intellectual
disability and older participants. The previously reported VABS "autism profile"
was not observed. Current findings clarify previous research and will inform the
diagnostic process and treatment planning.
PMID- 25117585
TI - In vivo imaging in the rabbit as a model for the study of ovulation-inducing
factors.
AB - The study of factors responsible for eliciting ovulation in rabbits has been
hampered by the lack of a suitable method of monitoring the ovaries in vivo.
Ovarian imaging by ultrasound biomicroscopy was used in two experiments designed
to determine the effects of seminal plasma on the ovulatory response in rabbits.
In Experiment 1, female rabbits were group-housed and treated intramuscularly
with saline, gonadotropin releasing hormone (GnRH), or seminal plasma of llamas
or rabbits (n = 4 to 6 per group). Rabbits were euthanized eight days later to
evaluate the ovarian response by ultrasound biomicroscopy ex situ. No differences
among groups were detected in the proportion of rabbits that ovulated or in the
number and size of corpora lutea. The high incidence of ovulation in the negative
control group was unexpected, and confounded determination of an ovulation
inducing effect of seminal plasma. In Experiment 2, female rabbits were caged
individually, and treated as in Experiment 1 (n = 5 to 7 per group). The ovarian
response was evaluated in vivo by transcutaneous ultrasound biomicroscopy.
Ovulation and formation of corpora lutea were detected only in rabbits given
GnRH. A preovulatory surge in plasma luteinizing hormone concentration and a post
ovulatory rise in plasma progesterone concentration were detected only in rabbits
treated with GnRH. Surgical translocation of the ovaries to a subcutaneous
position enabled longitudinal assessment of the ovulatory response by ultrasound
biomicroscopy. Results clearly documented the effect of physical/social
interaction on ovulation in rabbits, and did not support the hypothesis that
seminal plasma elicits ovulation in rabbits.
PMID- 25117586
TI - Effect of multilevel laboratory rat caging system on the well-being of the singly
housed Sprague Dawley rat.
AB - Current regulations emphasize that good husbandry practices allow animals to
engage in species appropriate postural adjustments without touching the enclosure
walls. This study evaluated the well-being of rats housed in a commercially
available multilevel rat caging system, with or without access to the upper level
of the caging. The evaluation methodologies included assessment of behavioral
observations in the home cage, physiological assessment of metabolism and immune
function, and determination of the affective state using a spatial cognitive bias
assay. The study determined that rats that were provided access to the full
multilevel cage during testing after initial restriction to the lower level of
the cage demonstrated behavioral changes consistent with a positive affective
state, while those with no changes to their housing situation had no significant
differences in their affective states. Rats that were consistently housed with
access restricted to the lower level of the cage exhibited a tendency to
increased neutrophil:lymphocyte ratios as compared with those provided with
access to all levels of the multilevel cage. There were no differences in body
weight demonstrated between the experimental groups. Overall use of the cage
space, as documented through analysis of behavioral observations in the home
cage, demonstrated no significant differences in preferred location in the cage
during the light or dark cycles, though rats with access to both levels of the
cage were significantly more active during the light cycle. The results of this
study suggest that the use of a multilevel caging system may improve the well
being of rats used in research.
PMID- 25117587
TI - Post-operative echocardiographic evaluation of bioprosthetic mitral valve
implantation in sheep.
AB - The ovine model is generally considered to be the best for testing bioprosthetic
heart valve durability. Although echocardiography is the method of choice for the
interim evaluation of the valve, literature on sheep echocardiography is scarce.
Within the context of a study on treatment of pericardial heart valve prostheses,
19 adolescent sheep underwent transthoracic echocardiography six days after
mitral implantation of bioprosthetic valves. Echocardiographic examination was
performed under mild anesthesia and animals were put in a right lateral decubitus
position. Four images were obtained: right parasternal long axis four and five
chamber views, right parasternal long axis view with left ventricular outflow,
and right parasternal short axis view through the mitral valve. We measured
aortic annulus and velocity time integral over the aortic valve to determine
stroke volume, cardiac output and cardiac index. The mitral valve was evaluated
through color Doppler imaging for valvular and paravalvular leakages. Pulsed wave
spectral Doppler was used for the measurement of velocities, pressures and
velocity time integrals. For the evaluation of valve stenosis deceleration time
and pressure half-time were determined. Effective orifice area of the mitral
valve was derived. And, although not measured, other structures could clearly be
visualized: right and left ventricle and atrium, wall thicknesses, tricuspid
valve. This study shows that echocardiography in sheep is feasible, and that
right parasternal images, obtained in animals in a right lateral decubitus
position, are well qualified for the interim evaluation of bioprosthetic valves
implanted in the mitral position. Besides the implanted valve, other cardiac
structures like atria and ventricles can be visualized and evaluated.
PMID- 25117588
TI - Practical precautionary resource management using robust optimization.
AB - Uncertainties inherent in fisheries motivate a precautionary approach to
management, meaning an approach specifically intended to avoid bad outcomes.
Stochastic dynamic optimization models, which have been in the fisheries
literature for decades, provide a framework for decision making when uncertain
outcomes have known probabilities. However, most such models incorporate
population dynamics models for which the parameters are assumed known. In this
paper, we apply a robust optimization approach to capture a form of uncertainty
nearly universal in fisheries, uncertainty regarding the values of model
parameters. Our approach, developed by Nilim and El Ghaoui (Oper Res 53(5):780
798, 2005), establishes bounds on parameter values based on the available data
and the degree of precaution that the decision maker chooses. To demonstrate the
applicability of the method to fisheries management problems, we use a simple
example, the Skeena River sockeye salmon fishery. We show that robust
optimization offers a structured and computationally tractable approach to
formulating precautionary harvest policies. Moreover, as better information about
the resource becomes available, less conservative management is possible without
reducing the level of precaution.
PMID- 25117589
TI - Early response of soil properties and function to riparian rainforest
restoration.
AB - Reforestation of riparian zones is increasingly practiced in many regions for
purposes of biodiversity conservation, bank stabilisation, and improvement in
water quality. This is in spite of the actual benefits of reforestation for
recovering underlying soil properties and function remaining poorly understood.
Here we compare remnant riparian rainforest, pasture and reforestation plantings
aged 2-20 years in an Australian subtropical catchment on ferrosols to determine
the extent to which reforestation restores key soil properties. Of the nine soil
attributes measured (total nitrogen, nitrate and ammonium concentrations, net
nitrification and ammonification rates, organic carbon, bulk density, fine root
biomass and water infiltration rates), only infiltration rates were significantly
lower in pasture than remnant riparian rainforest. Within reforestation
plantings, bulk density decreased up to 1.4-fold and infiltration rates increased
up to 60-fold with time post-reforestation. Our results suggest that the main
outcome of belowground processes of early reforestation is the recovery of the
soils' physical structure, with potential beneficial ecosystem services including
reduced runoff, erosion and associated sediment and nutrient loads in waterways.
We also demonstrate differential impacts of two commonly planted tree species on
a subset of soil properties suggesting that preferential planting of select
species could accelerate progress on specific restoration objectives.
PMID- 25117590
TI - A technique for the estimation of fractional moving blood volume by using three
dimensional power Doppler US.
AB - PURPOSE: To (a) demonstrate an image-processing method that can automatically
measure the power Doppler signal in a three-dimensional ( 3D three-dimensional )
ultrasonographic (US) volume by using the location of organs within the image and
(b) compare 3D three-dimensional fractional moving blood volume ( FMBV fractional
moving blood volume ) results with commonly used, unstandardized measures of 3D
three-dimensional power Doppler by using the human placenta as the organ of
interest. MATERIALS AND METHODS: This is a retrospective study of scans obtained
as part of a prospective study of imaging placental biomarkers with US, performed
with ethical approval and written informed consent. One hundred forty-three
consecutive female patients were examined by using an image-processing technique.
Three-dimensional FMBV fractional moving blood volume was measured on the
vasculature from the uteroplacental interface to a depth 5 mm into the placenta
by using a normalization volume 10 mm outside the uteroplacental interface and
compared against the Virtual Organ Computer-aided AnaLysis ( VOCAL Virtual Organ
Computer-aided AnaLysis ; GE Healthcare, Milwaukee, Wis) vascularization flow
index ( VFI vascularization flow index ). Intra- and interobserver variability
was assessed in a subset of 18 volumes. Wilcoxon signed rank test and intraclass
correlation coefficients were used to assess measurement repeatability. RESULTS:
The mean 3D three-dimensional FMBV fractional moving blood volume value +/-
standard deviation was 11.78% +/- 9.30 (range, 0.012%-44.16%). Mean VFI
vascularization flow index was 2.26 +/- 0.96 (range, 0.15-6.06). Linear
regression of VFI vascularization flow index versus FMBV fractional moving blood
volume produced an R(2) value of 0.211 and was significantly different in
distribution (P < .001). Intraclass correlation coefficient analysis showed
higher FMBV fractional moving blood volume values than VFI vascularization flow
index for intra- and interobserver variability; intraobserver values were 0.95
for FMBV fractional moving blood volume (95% confidence interval [ CI confidence
interval ]: 0.90, 0.98) versus 0.899 for VFI vascularization flow index (95% CI
confidence interval : 0.78, 0.96), and interobserver values were 0.93 for FMBV
fractional moving blood volume (95% CI confidence interval : 0.82, 0.97) versus
0.67 for VFI vascularization flow index (95% CI confidence interval : 0.32,
0.86). CONCLUSION: The extension of an existing two-dimensional standardized
power Doppler measurement into 3D three-dimensional by using an image-processing
technique was shown in an in utero placental study. Three-dimensional FMBV
fractional moving blood volume and VFI vascularization flow index produced
significantly different results. FMBV fractional moving blood volume performed
better than VFI vascularization flow index in repeatability studies. Further
studies are needed to assess accuracy against a reference standard.
PMID- 25117591
TI - Incidental pancreatic cystic lesions: is there a relationship with the
development of pancreatic adenocarcinoma and all-cause mortality?
AB - PURPOSE: To establish the effect of incidental pancreatic cysts found by using
computed tomographic (CT) and magnetic resonance (MR) imaging on the incidence of
pancreatic ductal adenocarcinoma and overall mortality in patients from an inner
city urban U.S. tertiary care medical center. MATERIALS AND METHODS:
Institutional review board granted approval for the study and waived the informed
consent requirement. The study population comprised cyst and no-cyst cohorts
drawn from all adults who underwent abdominal CT and/or MR November 1, 2001, to
November 1, 2011. Cyst cohort included patients whose CT or MR imaging showed
incidental pancreatic cysts; no-cyst cohort was three-to-one frequency matched by
age decade, imaging modality, and year of initial study from the pool without
reported incidental pancreatic cysts. Patients with pancreatic cancer diagnosed
within 5 years before initial CT or MR were excluded. Demographics, study
location (outpatient, inpatient, or emergency department), dates of pancreatic
adenocarcinoma and death, and modified Charlson scores within 3 months before
initial CT or MR examination were extracted from the hospital database. Cox
hazard models were constructed; incident pancreatic adenocarcinoma and mortality
were outcome events. Adenocarcinomas diagnosed 6 months or longer after initial
CT or MR examination were considered incident. RESULTS: There were 2034 patients
in cyst cohort (1326 women [65.2%]) and 6018 in no-cyst cohort (3,563 [59.2%]
women); respective mean ages were 69.9 years +/- 15.1(standard deviation) and
69.3 years +/- 15.2, respectively (P = .129). The relationship between mortality
and incidental pancreatic cysts varied by age: hazard ratios were 1.40 (95%
confidence interval [ CI confidence interval ]: 1.13, 1.73) for patients younger
than 65 years and 0.97 (95% CI confidence interval : 0.88, 1.07), adjusted for
sex, race, imaging modality, study location, and modified Charlson scores.
Incidental pancreatic cysts had a hazard ratio of 3.0 (95% CI confidence interval
: 1.32, 6.89) for adenocarcinoma, adjusted for age, sex, and race. CONCLUSION:
Incidental pancreatic cysts found by using CT or MR imaging are associated with
increased mortality for patients younger than 65 years and an overall increased
risk of pancreatic adenocarcinoma.
PMID- 25117592
TI - Structuring text and standardizing data for clinical and population health
applications.
PMID- 25117595
TI - Developing eLearning for pressure ulcer prevention and management.
AB - The impact of pressure ulcers is psychologically, physically and clinically
challenging for both patients and NHS staff. NHS Greater Glasgow and Clyde (NHS
GGC), in line with the Scottish Best Practice Statement for the Prevention and
Management of Pressure Ulcers ( Quality Improvement Scotland, 2009 ), and the NHS
Health Improvement Scotland (2011) Preventing Pressure Ulcers Change Package,
launched an awareness campaign throughout the organisation in April 2012 and has
more recently adopted a 'zero-tolerance' approach to pressure damage. The tissue
viability service in NHS GGC recognised that in order to achieve this aim,
education of front-line staff is essential. An educational framework for pressure
ulcer prevention was developed for all levels of healthcare staff involved in the
delivery of patient care. As a means to support the framework, an initiative to
develop web-based eLearning modules has been taken forward. This has resulted in
the creation of an accessible, cost-effective, stimulating, relevant, and
evidence-based education programme designed around the educational needs of all
healthcare staff. In conjunction with the organisation's 'top ten tools' for
pressure ulcer prevention and management, the modular online education programme
addresses the aims of quality improvement and zero tolerance by supporting the
provision of safe and effective person-centered care.
PMID- 25117596
TI - Prevention and management of wounds using compression therapy.
PMID- 25117597
TI - Use of a coverlet system for the management of skin microclimate.
AB - Pressure and shear are the two key extrinsic factors that cause pressure ulcer
damage. However, if the resilience of the skin and soft tissue deteriorates, the
individual's susceptibility to such pressure damage will increase. The risk is
greater if the microclimate at the interface between the skin and the support
surface is impaired. This will occur when the skin temperature is elevated and
there is excess moisture on the skin surface. Microclimate management therefore
plays an important role in pressure ulcer prevention. This article describes how
use of a new coverlet system (Skin IQ Microclimate Manager, ArjoHuntleigh) can
avoid the accumulation of heat and moisture at the patient/support-surface
interface.
PMID- 25117594
TI - Treatment adherence among new triptan users: a 2-year cohort study in Taiwan.
AB - BACKGROUND: The persistence of triptan use among newly prescribed users is low in
the United States and European countries. However, triptan refill patterns in
Asian primary care practices have not been well described. METHODS: Data from the
National Health Insurance Research Database in Taiwan were used to conduct a
retrospective cohort analysis from 2005 to 2008. All participants were followed
for 2 years after receiving a new triptan prescription. Refill and 2-year
retention rates of newly prescribed triptans were calculated, and predictors of
the first triptan refill and 2-year retention were analyzed. RESULTS: Of the
13,951 participants with a new triptan prescription (99.9% sumatriptan), 67.4%
were prescribed by a neurologist, 67.4% were prescribed at least one prophylactic
agent for migraine. Of them, 34.3% adhered to the newly prescribed triptan at the
first refill, 0.01% switched to another triptan, and 40.9% switched to a non
triptan acute migraine medication. The 2-year retention rate was 4.0%. The
frequency of headache-related neurologic visits for 1 year before the index date,
first prescription of triptan or other acute medications, first triptan
prescription by a neurologist, and prophylactic use were associated with higher
first refill rates. The frequency of headache-related neurologic visits 1 year
before the index date and first triptan prescription by a neurologist were
related to higher 2-year retention rates. Diabetes mellitus and first triptan
prescription at a local medical clinic were associated with reduced probability
of continued triptan use at the first refill and 2 years. CONCLUSIONS: Similar to
Western societies, the refill and 2-year retention rates were low in new users of
triptans. Frequency of neurologic visits and triptan prescription by a
neurologist were significant predictors of adherence.
PMID- 25117598
TI - Wound imaging: from Waterloo to tomorrow.
PMID- 25117599
TI - A vapour-permeable film dressing used on superficial wounds.
AB - Films are an extremely versatile dressing type that can be effectively used in
the treatment of many superficial wounds, such as skin grafts, surgical wounds
and superficial burns; they provide an optimal moist environment to promote
healing, act as a barrier to bacteria, and afford protection from urine and
faecal contamination. Unfortunately, many film dressings are difficult to handle
and use traditional adhesives, which can cause trauma to the wound and
surrounding skin, as well as increased wound pain at dressing removal. Mepitel(r)
Film is a new, easy-to-use wound dressing designed with Safetac(r) technology
that helps to minimise dressing-related trauma and pain and assist undisturbed
wound healing. This article presents case studies that examine Mepitel Film's use
on a variety of wounds, and reviews the findings of research that was undertaken
to evaluate the benefits of using this recently developed dressing.
PMID- 25117600
TI - Pressure ulcer grading and appropriate equipment selection.
AB - This article explores the process and rationale for designing a poster to support
community nurses in selecting appropriate pressure-relieving equipment based on
accurate risk assessment and correct pressure ulcer grading. The project was
prompted by the requirement to update community nurses' knowledge and ensure
pressure-relieving equipment selection was evidence-based and not reliant on
personal preference. The 2012 NHS Midlands and East 'Stop the pressure' campaign
provided community nurses with a framework for pressure ulcer prevention and
management. The attention to support surfaces highlighted the need for
appropriate equipment. However the tissue viability team found that the
introduction of this pathway alone did not help with the practical issues of
appropriate equipment selection. The poster was designed with consideration as to
how adults learn, and by looking to the Plan, Do, Study, Act (PDSA) cycle. This
provided the framework for enabling new ideas and changes to practice to be
tested on a small scale before full implementation.
PMID- 25117601
TI - Using an alternating pressure mattress to offload heels in ICU.
AB - The heel continues to be one of the most common sites of pressure damage. This
article reviews the anatomy and physiology of the heel and explores significant
risk factors, including those found in the critically ill patient. Interventions
to prevent heel pressure ulceration by offloading the heel are explored. An
evaluation of the Nimbus 4 alternating pressure mattress was undertaken within an
intensive care unit (ICU) to consider the efficacy of its unique Wound Valve
Technology, which is designed to help prevent heel pressure ulceration. During
the evaluation period none of the patients using the Nimbus 4 developed a
pressure ulcer. Staff observed that the Wound Valves provided effective pressure
redistribution and, although the cells frequently needed to be adjusted, patient
safety was maintained throughout. The Wound Valves were most effective on
patients who were less prone to voluntary movement.
PMID- 25117602
TI - Extent of cortical generators visible on the scalp: effect of a subdural grid.
AB - The effect of the non-conducting substrate of a subdural grid on the scalp
electric potential distribution is studied through simulations. Using a detailed
head model and the finite element method we show that the governing physics
equations predict an important attenuation in the scalp potential for generators
located under the grid, and an amplification for generators located under holes
in the skull filled with conductive media. These effects are spatially localized
and do not cancel each other. A 4 * 8 cm grid can produce attenuations of 2 to 3
times, and an 8 * 8 cm grid attenuation of up to 8 times. As a consequence, when
there is no subdural grid, generators of 4 to 8 cm(2) produce scalp potentials of
the same maximum amplitude as generators of 10 to 20 cm(2) under the center of a
subdural grid. This means that the minimum cortical extents necessary to produce
visible scalp activity determined from simultaneous scalp and subdural recordings
can be overestimations.
PMID- 25117603
TI - Projecting my envy onto you: neurocognitive mechanisms of an offline emotional
egocentricity bias.
AB - Humans often project their own beliefs, desires and emotions onto others,
indicating an inherent egocentrism. In five studies we investigated the
neurocognitive mechanisms underlying emotional egocentricity bias (EEB) and
specifically an offline EEB, defined as the projection of one's own tendency to
react with a certain emotional response pattern in a given situation onto other
people. We used a competitive reaction time game associated with monetary gains
and losses that allowed inducing feelings of envy and Schadenfreude. While we
found evidence for the first hand experience of envy and Schadenfreude, we also
observed an offline bias, that is participants on average projected feelings of
envy and Schadenfreude when having to judge others. Importantly the extent of
experienced and projected social emotions were highly correlated. This bias was
observed when participants were both directly involved and also as an uninvolved
party, suggesting the offline bias to be independent of the presently experienced
emotion. Under increased time pressure however an online bias emerged whereby
participants just projected their presently experienced emotions onto the other.
Finally, we show that on the neural level shared neuronal networks underlie the
offline EEB at least for envy. Thus, for envy, activity of the same part of
anterior insula was sensitive to individual differences both in the experience
and the projection of envy. These findings outline the set of circumstances
leading to specific types of empathic attribution biases and show that individual
differences in the experience of social emotions are predictive of the offline
egocentricity bias both on a behavioral as well as a neural level. These data
extend present models on the neurocognitive mechanisms of interpersonal
understanding in the socio-affective domain.
PMID- 25117604
TI - Nasal chondromesenchymal hamartoma in young children: CT and MRI findings and
review of the literature.
AB - BACKGROUND: Nasal chondromesenchymal hamartoma (NCMH) is an extremely rare benign
tumor, primarily diagnosed in young infants and children and it often simulates
malignant tumors on imaging. CASE PRESENTATION: We present computerized
tomography and magnetic resonance imaging findings of two nasal
chondromesenchymal hamartomas in a 5-year-old boy and a 6-week-old girl.
CONCLUSIONS: NCMH is a rare, benign tumor-like lesion with good biologic
behavior. No recurrence after complete resection or malignant transformation of
NCMH has been reported. A correct diagnosis is imperative to avoid unnecessary
adjuvant therapy.
PMID- 25117605
TI - AFM analysis of the multiple types of molecular interactions involved in
rituximab lymphoma therapy on patient tumor cells and NK cells.
AB - Rituximab is a monoclonal antibody drug approved for the treatment of patients
with lymphomas. Rituximab's main killing mechanism is antibody-dependent cellular
cytotoxicity (ADCC). During ADCC, rituximab's fragment antigen binding (Fab)
region binds to the CD20 antigen on the tumor cell and its fragment
crystallizable (Fc) region binds to the Fc receptor (FcR) on the natural killer
(NK) cells. In this study, two types of molecular interactions (CD20-rituximab,
FcR-rituximab) involved in ADCC were measured simultaneously on cells prepared
from biopsy specimens of lymphoma patients by utilizing atomic force microscopy
(AFM) with functionalized tips carrying rituximab. NK cells were detected by
specific NKp46 fluorescent labeling and tumor cells were detected by specific
ROR1 fluorescent labeling. Based on the fluorescence recognition, the binding
affinity and distribution of FcRs on NK cells, and CD20 on tumor cells, were
quantitatively measured and mapped. The binding affinity and distribution of FcRs
(on NK cells) and CD20 (on tumor cells) were associated with rituximab clinical
efficacy. The experimental results provide a new approach to simultaneously
quantify the multiple types of molecular interactions involved in rituximab ADCC
mechanism on patient biopsy cells, which is of potential clinical significance to
predict rituximab efficacy for personalized medicine.
PMID- 25117606
TI - Mirandese language and genetic differentiation in Iberia: a study using X
chromosome markers.
AB - BACKGROUND: In the Iberian Peninsula, the Mirandese dialect, spoken in Miranda do
Douro (Portugal) close to the north-eastern border with Spain, has attracted much
attention. Aim, subjects and methods: This study focuses on providing further
insight into the connections forged between Miranda do Douro and regions in the
nearby Province of Zamora. This is in order to better assess the extent to which
such relations could have been detained by the current patterns of genetic
diversity of the populations, whilst contributing to refining the knowledge on
patterns of micro-differentiation within the Peninsula. The genetic
characterization of both populations was performed through the analysis of X
chromosomal markers: X-STRs and X-indels. RESULTS AND CONCLUSION: The results
showed that Miranda do Douro tended to present slightly lower levels of diversity
in comparison to the other studied regions, which can be a discreet sign of
isolation of that population over the years that might have led the way to the
preservation of a language not spoken anywhere else in the country. The analysis
of X-STRs particularly brought to light the presence of a subtle population sub
structure at the micro-geographical area encompassing the north-eastern border,
which seems to portray the importance of the political border as a mechanism
withholding gene flow between the two countries.
PMID- 25117607
TI - Urodynamics before stress urinary incontinence surgery.
AB - PURPOSE OF REVIEW: In patients with symptoms of stress urinary incontinence,
there is still a debate regarding the benefit of a multichannel urodynamic
investigation prior to surgical management. The purpose of this article is to
review recent evidence on this topic. RECENT FINDINGS: Results of two large
randomized controlled trials provided evidence that preoperative urodynamics do
not improve outcome of incontinence surgery in women with uncomplicated stress
urinary incontinence. Furthermore, in this selected group of women, urodynamics
hardly lead to deviation of surgery as a primary treatment in case of an
indication for operation based on symptoms and signs. Low urethral closure
pressures and detrusor overactivity are urodynamic parameters which were
associated with impaired cure of symptoms of stress urinary incontinence after
surgery. SUMMARY: Preoperative urodynamics do not improve outcome in women with
complaints of stress incontinence and do hardly alter the treatment plan. It
remains questionable whether a more accurate counselling on the postoperative
perspectives counterbalances the disadvantages attended with urodynamics. The
routine use in women with uncomplicated stress incontinence should no longer be
advised. Preoperative urodynamic evaluation should only be used to answer a
specific clinical question or if the results are likely to influence the choice
of treatment.
PMID- 25117615
TI - Phase-1 study of abiraterone acetate in chemotherapy-naive Japanese patients with
castration-resistant prostate cancer.
AB - Persistent androgen synthesis under castration status in adrenal gland, testes
and tumor cells is thought to be one of the major causes of development and
progression of castration-resistant prostate cancer (CRPC). Abiraterone acetate
(AA), the prodrug of abiraterone, which is an inhibitor of androgen synthesis
enzymes, was evaluated for pharmacokinetics, pharmacodynamics, preliminary
efficacy and safety in Japanese patients with CRPC in a phase-1, open-label and
dose-escalation study. Chemotherapy-naive Japanese CRPC patients (N = 27)
received one of four AA daily doses (250 mg [n = 9], 500 mg [n = 6], 1000 [1 h
premeal] mg [n = 6] and 1000 [2 h postmeal] mg [n = 6]) continuously through 28
day treatment cycles. In the first cycle, AA monotherapy was given on days 1-7
for pharmacokinetics, and AA plus prednisone (5 mg twice daily) from days 8 to
28. Of 27 patients, 9 continued treatment with AA until the data cut-off date (18
July 2013). Over the evaluated dose range, plasma abiraterone concentrations
increased with dose, with median tmax 2-3 h. At each dose level, mean serum
corticosterone concentrations increased, while testosterone and
dehydroepiandrosterone sulfate concentrations rapidly decreased following a
single AA dose and were further reduced to near the quantification limit on day 8
regardless of the dose. At least 3 patients from each dose-group experienced
>=50% prostate-specific antigen reduction, suggesting clinical benefit from AA in
Japanese CRPC patients. AA was generally well-tolerated, and, therefore, the
recommended AA dosage regimen in Japanese CRPC patients is 1000 mg oral dose
under modified fasting conditions (at least 1 h premeal or 2 h postmeal). This
study is registered at ClinicalTrials.gov: NCT01186484.
PMID- 25117616
TI - Forecasting spring from afar? Timing of migration and predictability of phenology
along different migration routes of an avian herbivore.
AB - Herbivorous birds are hypothesized to migrate in spring along a seasonal gradient
of plant profitability towards their breeding grounds (green wave hypothesis).
For Arctic breeding species in particular, following highly profitable food is
important, so that they can replenish resources along the way and arrive in
optimal body condition to start breeding early. We compared the timing of
migratory movements of Arctic breeding geese on different flyways to examine
whether flyways differed in the predictability of spring conditions at stopovers
and whether this was reflected in the degree to which birds were following the
green wave. Barnacle geese (Branta leucopsis) were tracked with solar GPS/ARGOS
PTTs from their wintering grounds to breeding sites in Greenland (N = 7),
Svalbard (N = 21) and the Barents Sea (N = 12). The numerous stopover sites of
all birds were combined into a set of 16 general stopover regions. The
predictability of climatic conditions along the flyways was calculated as the
correlation and slope between onsets of spring at consecutive stopovers. These
values differed between sites, mainly because of the presence or absence of
ecological barriers. Goose arrival at stopovers was more closely tied to the
local onset of spring when predictability was higher and when geese attempted
breeding that year. All birds arrived at early stopovers after the onset of
spring and arrived at the breeding grounds before the onset of spring, thus
overtaking the green wave. This is in accordance with patterns expected for
capital breeders: first, they must come into condition; at intermediate
stopovers, arrival with the food quality peak is important to stay in condition,
and at the breeding grounds, early arrival is favoured so that hatching of young
can coincide with the peak of food quality. Our results suggest that a chain of
correlations between climatic conditions at subsequent stopovers enables geese to
closely track the green wave. However, the birds' precision of migratory timing
seems uninfluenced by ecological barriers, indicating partly fixed migration
schedules. These might become non-optimal due to climate warming and preclude
accurate timing of long-distance migrants in the future.
PMID- 25117617
TI - Aromatase inhibitors for metastatic male breast cancer: molecular, endocrine, and
clinical considerations.
AB - Male breast cancer is a rare condition. Aromatase inhibitors are widely used for
treating metastatic male breast cancer patients. In this setting, their use is
not substantiated by prospective clinical trials, but is rather driven by
similarities supposedly existing with breast cancer in postmenopausal women. This
oversimplified approach was questioned by studies addressing the molecular and
endocrine roots of the disease. In this manuscript, we discuss relevant aspects
of the current use of aromatase inhibitors in metastatic male breast cancer in
light of the most updated evidence on the molecular landscape of the disease and
the specific changes in the hormonal background occurring with aging. We further
point to strategies for blocking multiple hormonal pathway nodes with the goal of
improving their therapeutic potential. We searched PubMed from its inception
until March 2014 for relevant literature on the use of aromatase inhibitors in
metastatic male breast cancer. Selected terms were combined and used both as
medical headings and text words. The reference list of the suitable manuscripts
was inspected for further publications. Aromatase inhibitors represent the
mainstay of treatment in the metastatic setting. Yet, efforts aimed at sharpening
the therapeutic potential of aromatase inhibitors still pose a challenge due to
the paucity of data. The choice of dual hormonal (or sequential) therapy
combining aromatase inhibitors with a GnRH analogue may represent a valid
alterative, particularly if informed by cancer- and patient-related features
including molecular, endocrine, and clinic characteristics.
PMID- 25117618
TI - Electrodeposition of magnetic, superhydrophobic, non-stick, two-phase Cu-Ni foam
films and their enhanced performance for hydrogen evolution reaction in alkaline
water media.
AB - Two-phase Cu-Ni magnetic metallic foams (MMFs) with tunable composition have been
prepared by electrodeposition taking advantage of hydrogen co-evolution as a
source of porosity. It is observed that Ni tends to deposit inside the porous
network defined by the Cu building blocks. Contact angle measurements reveal that
the prepared porous films show a remarkable superhydrophobicity (contact angle
values larger than 150 degrees ) and a non-sticking property to aqueous droplets.
This behavior is predominately ascribed to the morphology of the films -
hierarchical micro/nanoporosity, wall thickness, and spatial arrangement. The
electrochemical activity and stability towards hydrogen evolution reaction of the
Cu-Ni MMFs has been investigated by cyclic voltammetry in 1 M KOH at 298 K, and
the optimal Ni content is found to be 15 at%. Furthermore, all the foam-like
films exhibit ferromagnetic behaviour due to the presence of the Ni-rich phase,
with coercivity values ranging from 114 Oe to 300 Oe. From the technological
point of view, the Cu-Ni MMFs are promising candidates for magnetically-actuated
micro/nano-electromechanical systems (MEMS/NEMS) and micro/nanorobotic platforms
with a large surface-area to volume ratio or in magnetic sensors or separators.
PMID- 25117619
TI - The role of physical activity in the CKD setting.
AB - A sedentary lifestyle contributes to the development of cardiovascular disease,
hypertension, diabetes and probably cancer in the general population; this
cluster of disease may be defined the diseasome of physical inactivity. Also in
CKD/ESRD patients physical activity is strikingly low. As a result of growing
evidence suggestive of cardiovascular benefit among the CKD population with
exercise, the National Kidney Foundation recommended counseling by nephrologists
to increase patients' levels of physical activity in their guideline about
management of cardiovascular disease. Therefore, to maintain the well-being and
functional capacity of renal patients attention should be directed toward
maintaining strength and aerobic fitness as well as focusing on renal function
and anemia or other comorbidities. All CKD/ESRD patients should be counseled and
regularly encouraged by nephrology and dialysis staff to increase their level of
physical activity.
PMID- 25117620
TI - Acute Carotid Artery Stent Thrombosis Due to Dual Antiplatelet Resistance.
AB - Carotid artery stenting (CAS) is a revascularization modality that is an
alternative to carotid endarterectomy. The efficacy of CAS in primary and
secondary prevention from ischemic stroke has been demonstrated in various
trials. Acute thrombosis of CAS is a rare complication that can lead to dramatic
and catastrophic consequences. We discuss a case of acute CAS thrombosis in a
patient who had previously undergone successful CAS. CAS was performed in a 73
year-old man who had had dysarthria lasting 2 weeks with 95% stenosis in his left
internal carotid artery. An acute cerebrovascular event resulting in right-sided
hemiplegia developed 24 h after the procedure. Computed tomographic carotid
angiography revealed complete occlusion of the stent with thrombus. The cause of
stent thrombosis was thought to be antiaggregant resistance to both
acetylsalicylic acid and clopidogrel. The most important cause of acute CAS
thrombosis is inadequate or ineffective antiaggregant therapy. Evaluating
patients who are candidates for CAS for acetylsalicylic acid and clopidogrel
resistance may preclude this complication.
PMID- 25117621
TI - Transforming growth factor alpha is a critical mediator of radiation lung injury.
AB - Radiation fibrosis of the lung is a late toxicity of thoracic irradiation.
Epidermal growth factor (EGF) signaling has previously been implicated in
radiation lung injury. We hypothesized that TGF-alpha, an EGF receptor ligand,
plays a key role in radiation-induced fibrosis in lung. Mice deficient in
transforming growth factor (TGF-alpha(-/-)) and control C57Bl/6J (C57-WT) mice
were exposed to thoracic irradiation in 5 daily fractions of 6 Gy. Cohorts of
mice were followed for survival (n >= 5 per group) and tissue collection (n = 3
per strain and time point). Collagen accumulation in irradiated lungs was
assessed by Masson's trichrome staining and analysis of hydroxyproline content.
Cytokine levels in lung tissue were assessed with ELISA. The effects of TGF-alpha
on pneumocyte and fibroblast proliferation and collagen production were analyzed
in vitro. Lysyl oxidase (LOX) expression and activity were measured in vitro and
in vivo. Irradiated C57-WT mice had a median survival of 24.4 weeks compared to
48.2 weeks for irradiated TGF-alpha(-/-) mice (P = 0.001). At 20 weeks after
irradiation, hydroxyproline content was markedly increased in C57-WT mice exposed
to radiation compared to TGF-alpha(-/-) mice exposed to radiation or unirradiated
C57-WT mice (63.0, 30.5 and 37.6 MUg/lung, respectively, P = 0.01). C57-WT mice
exposed to radiation had dense foci of subpleural fibrosis at 20 weeks after
exposure, whereas the lungs of irradiated TGF-alpha (-/-) mice were largely
devoid of fibrotic foci. Lung tissue concentrations of IL-1beta, IL-4, TNF-alpha,
TGF-beta and EGF at multiple time points after irradiation were similar in C57-WT
and TGF-alpha(-/-) mice. TGF-alpha in lung tissue of C57-WT mice rose rapidly
after irradiation and remained elevated through 20 weeks. TGF-alpha(-/-) mice had
lower basal LOX expression than C57-WT mice. Both LOX expression and LOX activity
were increased after irradiation in all mice but to a lesser degree in TGF-alpha(
/-) mice. Treatment of NIH-3T3 fibroblasts with TGF-alpha resulted in increases
in proliferation, collagen production and LOX activity. These studies identify
TGF-alpha as a critical mediator of radiation-induced lung injury and a novel
therapeutic target in this setting. Further, these data implicate TGF-alpha as a
mediator of collagen maturation through a TGF-beta independent activation of
lysyl oxidase.
PMID- 25117623
TI - The influence of dose rate on the induction of chromosome aberrations and gene
mutation after exposure of plateau phase V79-4 cells with high-LET alpha
particles.
AB - While protracting exposures of low-LET radiations usually leads to a reduction in
their effectiveness for a given dose, for high-LET radiation there is now
substantial evidence for what has been called an inverse dose-rate effect, where
under certain circumstances there is an increase in carcinogenesis or other
biological effects, with decreasing dose rate. This study investigates the
influence of dose rate on the induction of chromosome aberrations and gene
mutations after irradiation of plateau phase V79-4 cells with high-LET alpha
particles. The induction of chromosomal aberrations exhibited a linear
relationship with dose and showed evidence of a small but significant
conventional dose-rate dependence, with low-dose-rate exposures (0.28 Gy h(-1))
being less effective by about 20% (ratio 0.82 +/- 0.04) compared to acute
exposures. However no significant dose-rate effect was observed for cell survival
or the induction of mutations in the HPRT gene for low-dose-rate exposure (8.0 *
10(-5) and 1.5 * 10(-2) Gy h(-1) for exposure of 0.36 and 0.69 Gy, respectively)
when compared to acute exposures.
PMID- 25117622
TI - Wip1 abrogation decreases intestinal tumor frequency in APC(Min/+) mice
irrespective of radiation quality.
AB - Low-linear energy transfer (low-LET) gamma-ray exposure is a risk factor for
colorectal cancer (CRC). Due to their high-LET nature, energetic iron ions found
in space are expected to pose greater CRC risks to astronauts undertaking long
duration space missions beyond low Earth orbit. Wild-type p53-induced phosphatase
1 (Wip1) is important for cellular DNA damage response and its abrogation has
been shown to inhibit spontaneous intestinal tumorigenesis in APC(Min/+) mice, a
well-studied mouse model of human CRC. However, the relationship of Wip1 to
radiation-induced intestinal tumorigenesis, especially by energetic iron ions,
has not been investigated in APC(Min/+) mice. We have previously reported that
there is a greater intestinal tumorigenic potential of iron-ion radiation
relative to (137)Cs gamma rays, so the purpose of the current study was to
investigate whether Wip1 abrogation could influence high-LET dependent intestinal
tumorigenesis in APC(Min/+) mice. Intestinal tumor frequency and grade were
assessed in APC(Min/+)/Wip1(-/-) mice and results were compared to those in
APC(Min/+)/Wip1(+/+) mice after exposure to a mean absorbed dose of 2 Gy from
(137)Cs gamma rays or 1.6 Gy from 1 GeV/n iron ions. Cellular differentiation and
proliferation were also assessed in the intestinal tumors of sham-irradiated and
irradiated mice. Decreased tumor frequency and lower tumor grade were observed in
APC(Min/+)/Wip1(-/-) relative to APC(Min/+)/Wip1(+/+) mice. Notably, a similar
decrease (~6-fold in both groups) in tumor number was observed in sham-irradiated
and gamma-irradiated APC(Min/+)/Wip1(-/-) relative to APC(Min/+)/Wip1(+/+) mice.
However, tumorigenesis in the energetic iron-ion exposed group was reduced ~8
fold in APC(Min/+)/Wip1(-/-) relative to APC(Min/+)/Wip1(+/+) mice. A
significantly lower proliferation/differentiation index in tumors of iron-ion
exposed APC(Min/+)/Wip1(-/-) relative to APC(Min/+)/Wip1(+/+) mice suggests that
reduced proliferation and enhanced differentiation as a result of Wip1 abrogation
maybe involved. In conclusion, the current study demonstrated that the absence of
Wip1 blocked radiation-induced intestinal tumorigenesis irrespective of radiation
quality and has implications for developing preventive strategies against the
tumorigenic potential of radiation exposure on earth and in outer space.
PMID- 25117624
TI - Modeling dose deposition and DNA damage due to low-energy beta(-) emitters.
AB - One of the main issues of low-energy internal emitters concerns the very short
ranges of the beta particles, versus the dimensions of the biological targets.
Depending on the chemical form, the radionuclide may be more concentrated either
in the cytoplasm or in the nucleus of the target cell. Consequently, since in
most cases conventional dosimetry neglects this issue it may overestimate or
underestimate the dose to the nucleus and hence the biological effects. To assess
the magnitude of these deviations and to provide a realistic evaluation of the
localized energy deposition by low-energy internal emitters, the biophysical
track-structure code PARTRAC was used to calculate nuclear doses, DNA damage
yields and fragmentation patterns for different localizations of radionuclides in
human interphase fibroblasts. The nuclides considered in the simulations were
tritium and nickel-63, which emit electrons with average energies of 5.7 (range
in water of 0.42 MUm) and 17 keV (range of 5 MUm), respectively, covering both
very short and medium ranges of beta-decay products. The simulation results
showed that the largest deviations from the conventional dosimetry occur for
inhomogeneously distributed short-range emitters. For uniformly distributed
radionuclides selectively in the cytoplasm but excluded from the cell nucleus,
the dose in the nucleus is 15% of the average dose in the cell in the case of
tritium but 64% for nickel-63. Also, the numbers of double-strand breaks (DSBs)
and the distributions of DNA fragments depend on subcellular localization of the
radionuclides. In the low- and medium-dose regions investigated here, DSB numbers
are proportional to the nuclear dose, with about 50 DSB/Gy for both studied
nuclides. In addition, DSB numbers on specific chromosomes depend on the
radionuclide localization in the cell as well, with chromosomes located more
peripherally in the cell nucleus being more damaged by short-ranged emitters in
cytoplasm compared with chromosomes located more centrally. These results
illustrate the potential for over- or underestimating the risk associated with
low-energy emitters, particularly for tritium intake, when their distribution at
subcellular levels is not appropriately considered.
PMID- 25117625
TI - Nonhomologous end-joining repair plays a more important role than homologous
recombination repair in defining radiosensitivity after exposure to high-LET
radiation.
AB - DNA double-strand breaks (DSBs) induced by ionizing radiation pose a major threat
to cell survival. The cell can respond to the presence of DSBs through two major
repair pathways: homologous recombination (HR) and nonhomologous end joining
(NHEJ). Higher levels of cell death are induced by high-linear energy transfer
(LET) radiation when compared to low-LET radiation, even at the same physical
doses, due to less effective and efficient DNA repair. To clarify whether high
LET radiation inhibits all repair pathways or specifically one repair pathway,
studies were designed to examine the effects of radiation with different LET
values on DNA DSB repair and radiosensitivity. Embryonic fibroblasts bearing
repair gene (NHEJ-related Lig4 and/or HR-related Rad54) knockouts (KO) were used
and their responses were compared to wild-type cells. The cells were exposed to X
rays, spread-out Bragg peak (SOBP) carbon ion beams as well as with carbon, iron,
neon and argon ions. Cell survival was measured with colony-forming assays. The
sensitization enhancement ratio (SER) values were calculated using the 10%
survival dose of wild-type cells and repair-deficient cells. Cellular
radiosensitivity was listed in descending order: double-KO cells > Lig4-KO cells
> Rad54-KO cells > wild-type cells. Although Rad54-KO cells had an almost
constant SER value, Lig4-KO cells showed a high-SER value when compared to Rad54
KO cells, even with increasing LET values. These results suggest that with carbon
ion therapy, targeting NHEJ repair yields higher radiosensitivity than targeting
homologous recombination repair.
PMID- 25117626
TI - Ability of 18-fludeoxyglucose positron emission tomography/CT to detect
incidental cancer.
AB - OBJECTIVE: To determine the prevalence and clinical features of pathologically
proven incidental cancer (IC) detected by whole-body fluorine-18 fludeoxyglucose
((18)F-FDG) positron emission tomography (PET)/CT, as well as the incidence of
false-positive and false-negative results. METHODS: We retrospectively reviewed
reports derived from (18)F-FDG PET/CT images of 3079 consecutive patients with
known or suspected malignancies for 3 years. Discrete focal uptake indicating IC
was identified from reports as well as pathological or clinical diagnoses, and
the clinical courses were investigated. The false-positive result was defined as
uptake indicating IC but not pathologically confirmed as malignant during follow
up. The false-negative result was defined as pathologically proven IC detected by
another modality at initial clinical work-up or diagnosed during the follow-up
period. RESULTS: We found (18)F-FDG uptake indicating IC in 6.7% of all patients,
and IC was pathologically proven in 2.2% of all patients. The most common sites
were the colon, lung and stomach. The median survival duration of patients with
IC was 42 months. The results were false positive in 4.5% of all patients, and
the results were false negative in 2.3% of all patients. CONCLUSION: (18)F-FDG
PET/CT is a valuable tool for detecting IC. The rates of false-positive and false
negative results are within acceptable range. ADVANCES IN KNOWLEDGE: This is the
first report to describe the survival of patients with IC, and the detailed
features of false-negative results at actual clinical settings.
PMID- 25117627
TI - Prevention of hyperoxia-induced bronchial hyperreactivity by sildenafil and
vasoactive intestinal peptide: impact of preserved lung function and structure.
AB - OBJECTIVE: Hyperoxia exposure leads to the development of lung injury and
bronchial hyperreactivity (BHR) via involvement of nitric oxide (NO) pathway. We
aimed at characterizing whether the stimulation of the NO pathway by sildenafil
or vasoactive intestinal peptide (VIP) is able to prevent the hyperoxia-induced
development of BHR. The respective roles of the preserved lung volume and
alveolar architecture, the anti-inflammatory and anti-apoptotic potentials of
these treatments in the diminished lung responsiveness were also characterized.
MATERIALS AND METHODS: Immature (28-day-old) rats were exposed for 72 hours to
room air (Group C), hyperoxia (>95%, Group HC), or hyperoxia with the concomitant
administration of vasoactive intestinal peptide (VIP, Group HV) or sildenafil
(Group HS). Following exposure, the end-expiratory lung volume (EELV) was
assessed plethysmographically. Airway and respiratory tissue mechanics were
measured under baseline conditions and following incremental doses of
methacholine to assess BHR. Inflammation was assessed by analyzing the
bronchoalveolar lavage fluid (BALF), while biochemical and histological analyses
were used to characterize the apoptotic and structural changes in the lungs.
RESULTS: The BHR, the increased EELV, the aberrant alveolarization, and the
infiltration of inflammatory cells into the BALF that developed in Group HC were
all suppressed significantly by VIP or sildenafil treatment. The number of
apoptotic cells increased significantly in Group HC, with no evidence of
statistically significant effects on this adverse change in Groups HS and HV.
CONCLUSIONS: These findings suggest that stimulating the NO pathway by sildenafil
and VIP exert their beneficial effect against hyperoxia-induced BHR via
preserving normal EELV, inhibiting airway inflammation and preserving the
physiological lung structure, whereas the antiapoptotic potential of these
treatments were not apparent in this process.
PMID- 25117628
TI - Defining the recognition elements of Lewis Y-reactive antibodies.
AB - Antibody response to carbohydrate antigens is often independent of T cells and
the process of affinity/specificity improvement is considered strictly dependent
on the germinal centers. Antibodies induced during a T cell-independent type 2
(TI-2) response are less variable and less functionally versatile than those
induced with T cell help. The antigen specificity consequences of accumulation of
somatic mutations in antibodies during TI-2 responses of Marginal Zone (MZ) B
cells is a fact that still needs explanation. Germline genes that define
carbohydrate-reactive antibodies are known to sculpt antibody-combining sites
containing innate, key side-chain contacts that define the antigen recognition
step. However, substitutions associated with MZ B cell derived antibodies might
affect the mobility and polyspecificity of the antibody. To examine this
hypothesis, we analyzed antibodies reactive with the neolactoseries antigen Lewis
Y (LeY) to define the residue subset required for the reactive repertoire for the
LeY antigen. Our molecular simulation studies of crystallographically determined
and modeled antibody-LeY complexes suggests that the heavy-chain germline gene
VH7183.a13.20 and the light-chain Vkappa cr1 germline gene are sufficient to
account for the recognition of the trisaccharide-H determinant Types 1-4, while
the specificity for LeY is driven by the CDR3 backbone conformation of the heavy
chain and not the side chain interactions. These results confirm that these
monoclonals use germline-encoded amino acids to recognize simple carbohydrate
determinants like trisaccharide-H but relies on somatic mutations in the
periphery of the combining site to modify affinity for LeY through electrostatic
interactions that leads to their optimized binding. These observations bring
further attention to the role of mutations in T-cell independent antibodies to
distinguish self from non-self carbohydrate antigens.
PMID- 25117629
TI - Solubility assessment and on-line exposure confirmation in a patch-clamp assay
for hERG (human ether-a-go-go-related gene) potassium channel inhibition.
AB - INTRODUCTION: The hERG (human ether-a-go-go-related gene) potassium channel
(KV11.1) is an important anti-target in drug discovery as its inhibition by small
molecules has considerable promiscuity and is linked to an increased risk of the
potentially fatal ventricular arrhythmia torsade de pointes. Therefore, great
efforts are taken in the pharmaceutical industry to early on screen out compounds
that block the channel. Early screening activities most often include compounds
with sub-optimal physicochemical properties such as limited solubility.
Therefore, careful monitoring of achieved compound concentration importantly
supports the validity of experimental data. METHODS: A novel principle of
exposure confirmation in a constant flow patch-clamp assay for hERG interaction
is presented. Quantification is based on-real time UV absorption spectroscopy of
the perfusion solution using long light path fiber optic flow cells. Calibration
is performed using solutions which are confirmed by turbidometry to be free of
precipitates. RESULTS: Turbidometry is shown to be sensitive enough to ensure
valid calibration of the UV spectroscopic measurement. For a typical drug-like
small molecule (verapamil) it is shown that even 30 nM can be accurately
quantified using a 100 cm fiber optic flow cell. DISCUSSION: The combination of
turbidometry and long light path fiber optic UV spectroscopy offers accurate,
almost real-time exposure determination in a wide range of concentrations with
little effort, affordable instrumentation, and no delay for data reporting. For
research compounds with challenging physicochemical properties this method
provides valuable data to support the validity of the measurements.
PMID- 25117630
TI - Radiological analysis of gastrointestinal dysmotility in a model of central
nervous dopaminergic degeneration: comparative study with conventional in vivo
techniques in the rat.
AB - INTRODUCTION: Gastrointestinal (GI) motility disorders include many clinical
manifestations associated with various pathologies. They are widespread and can
be considered a primary symptom or can be associated to other diseases, such as
Parkinson's disease. Understanding the type and site of GI dysmotility is crucial
to identify the functional abnormality and to unravel the underlying mechanisms,
in order to design adequate therapeutic interventions. METHODS: In the present
study, we applied radiological analysis, a common tool in clinical practice, to
follow up in vivo the progression of GI dysmotility over time and along the
entire GI tract in an animal model of central nervous dopaminergic degeneration
and compared these results to those obtained with standard techniques commonly
used to assess GI motor functions in small rodents. RESULTS: Our radiological
data, showing delayed gastric emptying and constipation, agree with and expand
previous information obtained with other functional assays in the same model,
suggesting that radiological analysis can be an appropriate method to explore GI
dysmotility in animal models of human pathologies. DISCUSSION: In this study we
have applied for the first time the GI radiological analysis to an animal model
of central nervous dopaminergic degeneration providing a non-invasive/animal
preserving approach, ethically more acceptable and useful to follow up the
development of GI dysmotility in pathologies evolving over time.
PMID- 25117633
TI - Amyloid associated with neoplasia in two captive tricolour sharkminnows
Balantiocheilus melanopterus Bleeker.
AB - Amyloid associated with pancreatic adenocarcinoma was discovered in two captive
adult tricolour sharkminnows Balantiocheilus melanopterus Bleeker found dead in a
freshwater display. Enlarged abdomens expanded by bloody ascitic fluid and
grossly visible masses of abnormal tissue were present surrounding sections of
the stomach and intestine. Histologically, the masses were composed of areas of
well-organized exocrine pancreatic acini interspersed with cords of poorly
differentiated, spindle-shaped cells that compressed and effaced normal
parenchyma. These cells possessed small numbers of cytoplasmic zymogen granules;
the exocrine nature of these cells was confirmed using transmission electron
microscopy (TEM). Fibrovascular connective tissue of the hepatopancreas and
mesenteries was expanded by lightly eosinophilic, hyaline, homogeneous acellular
material. Similar material greatly expanded the tunica media of large blood
vessels in the hepatopancreas. After staining with Congo red or thioflavin T,
this material exhibited red-green dichroism under polarized light or bright green
fluorescence under ultraviolet light (255 nm), respectively. The non-branching
fibrils, of indeterminate length, had an approximate diameter of 10-20 nm using
TEM. Although exocrine pancreatic neoplasia is relatively common in fish, the
presence of amyloid is not. To our current knowledge, the latter has not yet been
described in association with a neoplastic lesion in fish.
PMID- 25117632
TI - The CELSR1 polymorphisms rs6007897 and rs4044210 are associated with ischaemic
stroke in Chinese Han population.
AB - BACKGROUND: Recently, CELSR1 was identified by genome-wide association studies
(GWAS) as a susceptibility gene for ischaemic stroke (IS) in Japanese
individuals. AIM: The goal was to examine whether CELSR1 variants are associated
with IS in the Chinese Han population. SUBJECTS AND METHODS: This study genotyped
two single nucleotide polymorphisms (SNPs) of CELSR1, rs6007897 and rs4044210, in
a Chinese sample of 569 IS cases and 581 controls and assessed their genotype and
allele associations with IS. RESULTS: The results showed that rs6007897 and
rs4044210 variants of CELSR1 were significantly (p < 0.01) associated with IS.
These associations remained after adjustment for age, gender, smoking status,
hypertension, diabetes mellitus and hypercholesterolemia. In addition, a
significant association was observed of rs6007897 and rs4044210 of CELSR1 with
large artery atherosclerosis (LAA), a sub-type of IS (p < 0.01). CONCLUSION:
Taken together, the present study has proven for the first time that CELSR1 is a
susceptibility gene for IS in the Chinese Han population, especially for LAA.
PMID- 25117631
TI - In vitro culture of bovine preantral follicles: a review.
AB - Preantral follicles are the majority of the ovarian follicle population and their
use as a source of homogeneous oocytes for bovine reproductive biotechnologies
could result in a substantial advance in this field. However, while in other
species embryos and offspring have been produced, in bovine species the results
have been limited to the follicular activation of small (primordial) preantral
follicles and formation of early antral follicles from large (secondary)
preantral follicles after in vitro culture. Therefore, this review will highlight
the basic aspects of bovine folliculogenesis by focusing on preantral follicles,
the methods of harvesting preantral follicles, the main results from in vitro
follicular culture during the last 20 years, and the potential candidate
substances (basic supplements, growth factors, and hormones) for improving the
efficiency of in vitro follicle growth.
PMID- 25117642
TI - Atypical neural responses to vocal anger in attention-deficit/hyperactivity
disorder.
AB - BACKGROUND: Deficits in facial emotion processing, reported in attention
deficit/hyperactivity disorder (ADHD), have been linked to both early perceptual
and later attentional components of event-related potentials (ERPs). However, the
neural underpinnings of vocal emotion processing deficits in ADHD have yet to be
characterised. Here, we report the first ERP study of vocal affective prosody
processing in ADHD. METHODS: Event-related potentials of 6-11-year-old children
with ADHD (n = 25) and typically developing controls (n = 25) were recorded as
they completed a task measuring recognition of vocal prosodic stimuli (angry,
happy and neutral). Audiometric assessments were conducted to screen for hearing
impairments. RESULTS: Children with ADHD were less accurate than controls at
recognising vocal anger. Relative to controls, they displayed enhanced N100 and
attenuated P300 components to vocal anger. The P300 effect was reduced, but
remained significant, after controlling for N100 effects by rebaselining. Only
the N100 effect was significant when children with ADHD and comorbid conduct
disorder (n = 10) were excluded. CONCLUSION: This study provides the first
evidence linking ADHD to atypical neural activity during the early perceptual
stages of vocal anger processing. These effects may reflect preattentive hyper
vigilance to vocal anger in ADHD.
PMID- 25117641
TI - Anti-tumor activity of WK88-1, a novel geldanamycin derivative, in gefitinib
resistant non-small cell lung cancers with Met amplification.
AB - Although epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs)
have been introduced for the treatment of non-small cell lung cancer (NSCLC), the
emergence of secondary T790M mutation in EGFR or amplification of the Met proto
oncogene restrain the clinical success of EGFR-TKIs. Since heat shock protein-90
(Hsp90) stabilizes various oncoproteins including EGFR and c-Met, the inhibition
of Hsp90 activity appears as a rational strategy to develop anticancer drugs.
Despite preclinical efficacy of geldanamycin-anasamycin (GA)-derivatives
containing benzoquinone moiety as Hsp90 inhibitors, the hepatotoxicity of these
GA-derivatives restricts their therapeutic benefit. We have prepared WK-88 series
of GA-derivatives, which lack the benzoquinone moiety. In this study, we have
examined the anticancer effects of WK88-1 in Met-amplified- and gefitinib
resistant (HCC827GR) NSCLC cells and its parental HCC827 cells. Treatment with
WK88-1 reduced the cell viability in both HCC827 and HCC827GR cells, which was
associated with marked decrease in the constitutive expression of Hsp90 client
proteins, such as EGFR, ErbB2, ErbB3, Met and Akt. Moreover, WK88-1 attenuated
phosphorylation of these Hsp90 client proteins and reduced the anchorage
independent growth of HCC827GR cells. Administration of WK88-1 did not cause
hepatotoxicity in animals and significantly reduced the growth of HCC827GR cells
xenograft tumors in nude mice. Our study provides evidence that ErbB3 might be a
client for Hsp90 in Met-amplified NSCLCs. In conclusion, we demonstrate that
inhibition of Hsp90 dampens the activation of EGFR- or c-Met-mediated survival of
Met-amplified NSCLCs and that WK88-1 as a Hsp90 inhibitor alleviates gefitinib
resistance in HCC827GR cells.
PMID- 25117644
TI - Mystery of myocardial midwall late enhancement?
PMID- 25117643
TI - Computer-aided CT coronary artery stenosis detection: comparison with human
reading and quantitative coronary angiography.
AB - To evaluate computer-aided stenosis detection for computed tomography coronary
angiography (CTA) in comparison with human reading and conventional coronary
angiography (CCA) as the reference standard. 50 patients underwent CTA and CCA
and out of these 44 were evaluable for computer-aided stenosis detection. The
diagnostic performance of the software and of human reading were compared and
quantitative coronary angiography (QCA) served as the reference standard for the
detection of significant stenosis (>50 %). Overall, three readers with high
(reader 1), intermediate (reader 2) and low (reader 3) experience in cardiac CT
imaging performed the manual CTA evaluation on a commercially available
workstation, whereas the automated software processed the datasets without any
human interaction. The prevalence of coronary artery disease was 41 % (18/44) and
QCA indicated significant stenosis (>50 %) in 33 coronary vessels. The automated
software accurately diagnosed 18 individuals with significant coronary artery
disease (CAD), and correctly ruled out CAD in 10 patients. In summary the
sensitivity of computer-aided detection was 100 %/94 % (per-patient/per-vessel)
and the specificity was 38 %/70 %, the positive predictive value (PPV) was 53
%/42 % and the negative predictive value (NPV) was 100 %/98 %. In comparison,
reader 1-3 showed per-patient sensitivities of 100/94/89 %, specificities of
73/69/50 %, PPVs of 72/68/55 % and NPVs of 100/95/87 %. Computer-aided detection
yields a high NPV that is comparable to more experienced human readers. However,
PPV is rather low and in the range of an unexperienced reader.
PMID- 25117647
TI - Hierarchically porous three-dimensional electrodes of CoMoO4 and ZnCo2O4 and
their high anode performance for lithium ion batteries.
AB - Ternary metal oxides have been receiving wide attention in electrochemical energy
storage due to their rich redox reactions and tuneable conductivity. We present a
simple solution-based method to prepare a 3D interconnected porous network of
ternary metal oxide (CoMoO4 and ZnCo2O4) nanostructures on macroporous nickel
foam. The open-structured networks with different degrees of porosity endow them
with high surface areas of electro-active sites. The Li ion storage properties of
both anodes are investigated. High rate capability and long term cycling
stability are achieved for both systems.
PMID- 25117648
TI - Nutrition and physical activity in CKD patients.
AB - Chronic kidney disease (CKD) patients are at risk for protein-energy wasting,
abnormal body composition and impaired physical capacity. These complications
lead to increased risk of hospitalization, morbidity and mortality.In CKD patient
as well as in healthy people, there is a close association between nutrition and
physical activity. Namely, inadequate nutrient (energy) intake impairs physical
performance thus favoring a sedentary lifestyle: this further contributes to loss
of muscle strength and mass, which limit the quality of life and rehabilitation
of CKD patients. In CKD as well as in end-stage-renal-disease patients, regular
physical activity coupled with adequate energy and protein intake counteracts
protein-energy wasting and related comorbidity and mortality. In summary,
exercise training can positively influence nutritional status and the perception
of well-being of CKD patients and may facilitate the anabolic effects of
nutritional interventions.
PMID- 25117646
TI - Tubal transport of gametes and embryos: a review of physiology and
pathophysiology.
AB - With the advent of assisted reproductive technology in the past three decades,
the clinical importance of fallopian tubes has been relatively overlooked.
However, successful spontaneous conception requires normal function of the tube
to provide not only a conduit for the gametes to convene and embryo to reach the
uterine cavity, but also a physiologically optimized environment for
fertilization and early embryonic development. In this review, after a brief
description of normal human tubal anatomy and histology, we will discuss tubal
transport and its principal effectors, including ciliary motion, muscular
contractility and tubal fluid. Furthermore, we will discuss the ciliary
ultrastructure and regulation of ciliary beat frequency by ovarian steroids,
follicular fluid, angiotensin system, autonomic nervous system and other factors
such as adrenomedullin and prostaglandins. In the last section, we describe the
adverse impact of various pathological conditions, such as endometriosis,
infection and smoking on tubal function and ciliary motility.
PMID- 25117650
TI - Oxidative stress and antioxidant status in patients with autoimmune liver
diseases.
AB - OBJECTIVE: To estimate oxidative stress and antioxidant components during
different stages of autoimmune liver diseases and assess their possible
implication on disease progression. METHODS: We determined several markers of
oxidative injury (isoprostane, aldehydes, protein carbonyls, 3-nitrotyrosine, and
myeloperoxidase) and antioxidant components (glutathione, glutathione peroxidase,
glutathione reductase, superoxide dismutase, and catalase) in whole blood, serum,
and urine in 49 patients with autoimmune cholestatic liver diseases (AC) and 36
patients with autoimmune hepatitis (AIH) and healthy subjects matched for sex and
age. RESULTS: Both AC and AIH patients had increased levels of all lipid and
protein oxidative injury products and significantly decreased whole blood
glutathione levels compared to controls. AIH patients had significantly higher
levels of aldehydes and glutathione peroxidase activity and significantly lower
protein carbonyl levels compared to AC patients. Protein carbonyl and isoprostane
levels increased and glutathione levels decreased gradually with progression from
mild fibrosis to severe fibrosis and cirrhosis in both AC and AIH patients. In
addition, both cirrhotic AC and AIH patients had significantly higher protein
carbonyls compared to non-cirrhotics. DISCUSSION: We provide novel findings in
support of a major contribution of oxidant/antioxidant imbalance in the
progression of liver injury in AC and AIH.
PMID- 25117651
TI - Anatomic connectivity assessed using pathway radial diffusivity is related to
functional connectivity in monosynaptic pathways.
AB - This work presents a pathway-dependent anatomic and functional connectivity
analysis in 19 patients with relapse-remitting multiple sclerosis (MS) and 16 age
, education-, and gender-matched controls. An MS population is used in this study
as a model for anatomic connectivity, permitting us to observe relationships
between anatomic and functional connectivity more easily. A combined resting
state functional magnetic resonance imaging (fMRI) and whole-brain, high angular
resolution diffusion imaging analysis is performed in three independent,
monosynaptic pathways. The pathways chosen were transcallosal pathway connecting
the bilateral primary sensorimotor regions, right and left posterior portion of
the Papez circuit, connecting the posterior cingulate cortex and hippocampus. The
Papez circuit is known to be involved in memory function, one of the most
frequently impacted cognitive domains in patients with MS. We show that anatomic
connectivity, as measured with diffusion-weighted imaging, and functional
connectivity, as measured with resting-state fMRI, are significantly reduced in
patients as compared with controls for at least some of the pathways considered.
In addition when all pathway measures are combined, anatomic and functional
connectivity are significantly correlated in patients with MS as well as healthy
controls. We suggest that anatomic and functional connectivity are related for
monosynaptic pathways and that radial diffusivity, as a diffusion-tensor-based
measure of white matter integrity, is a robust measure of anatomic connectivity
in the general population.
PMID- 25117649
TI - Effects of 20 standard amino acids on the growth, total fatty acids production,
and gamma-linolenic acid yield in Mucor circinelloides.
AB - Twenty standard amino acids were examined as single nitrogen source on the
growth, total fatty acids production, and yield of gamma-linolenic acid (GLA) in
Mucor circinelloides. Of the amino acids, tyrosine gave the highest biomass and
lipid accumulation and thus resulted in a high GLA yield with respective values
of 17.8 g/L, 23 % (w/w, dry cell weight, DCW), and 0.81 g/L, which were 36, 25,
and 72 % higher than when the fungus was grown with ammonium tartrate. To find
out the potential mechanism underlying the increased lipid accumulation of M.
circinelloides when grown on tyrosine, the activity of lipogenic enzymes of the
fungus during lipid accumulation phase was measured. The enzyme activities of
glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and ATP
citrate lyase were up-regulated, while NADP-isocitrate dehydrogenase was down
regulated by tyrosine during the lipid accumulation phase of the fungus which
suggested that these enzymes may be involved in the increased lipid biosynthesis
by tyrosine in this fungus.
PMID- 25117645
TI - A multi-faceted approach to understanding male infertility: gene mutations,
molecular defects and assisted reproductive techniques (ART).
AB - BACKGROUND: The assisted reproductive techniques aimed to assist infertile
couples have their own offspring carry significant risks of passing on molecular
defects to next generations. RESULTS: Novel breakthroughs in gene and protein
interactions have been achieved in the field of male infertility using genome
wide proteomics and transcriptomics technologies. CONCLUSION: Male Infertility is
a complex and multifactorial disorder. SIGNIFICANCE: This review provides a
comprehensive, up-to-date evaluation of the multifactorial factors involved in
male infertility. These factors need to be first assessed and understood before
we can successfully treat male infertility.
PMID- 25117653
TI - The indications, efficacy and adverse events of rituximab in a large cohort of
patients with juvenile-onset SLE.
AB - BACKGROUND: B cells drive antibody formation and T cell activation. This study
aimed to describe the clinical indications, efficacy and adverse events (AEs) for
the B-cell depleting agent, rituximab, in a large cohort of children with lupus.
METHODS: Prescribing records and the UK JSLE Cohort Study database identified
rituximab use. RESULTS: Sixty-three patients received 104 courses of intravenous
rituximab over a 10-year period. Patients were aged 12.2 (IQR 9.0-13.9) years at
diagnosis and 50 (79%) were female. They had disease for 1.4 (0.2-3.0) years at
the time of rituximab. Lupus nephritis was the most common indication (36% of
first courses). Clinical biomarkers, 2.5 (1.6-4.3) months after treatment,
demonstrated a statistically significant improvement in ESR, C3, C4, creatinine,
albumin, haemoglobin, anti-dsDNA titres and urine albumin:creatinine ratio. IgG,
IgA and IgM levels decreased (p < 0.01). Oral corticosteroid dose significantly
reduced after rituximab (dose before 0.26 (0.09-0.44) mg/kg, after 0.17 (0.09
0.30) mg/kg; p = 0.01)). AEs occurred in 19 (18%) of all courses including;
delayed second dose (8%), Ig replacement (2%) and infusion reactions (6%;
anaphylaxis 2%). The global BILAG score showed a trend toward improvement (before
4.5 (2.0-9.0), after 3.0 (2.0-5.0); p = 0.16). CONCLUSION: Rituximab improves
disease activity in children with lupus and serious AEs are infrequent.
Controlled studies are required.
PMID- 25117652
TI - Heck products of parthenolide and melampomagnolide-B as anticancer modulators
that modify cell cycle progression.
AB - (E)-13-(Aryl/heteroaryl)parthenolides (5a-i and 6a-i) were synthesized and
evaluated for their ability to modify cell cycle progression during progesterone
stimulated Xenopus oocyte maturation and screened for their anticancer activity
against a panel of 60 human cancer cell lines. (E)-13-(4-aminophenyl)
parthenolide (5b) caused a significant inhibition of progesterone-stimulated
oocyte maturation, and was determined to function downstream of MAP kinase
signaling, but upstream of the activation of the universal G2/M regulator, M
phase promoting factor (MPF), cyclin B/Cyclin-dependent kinase (CDK). The
compound (E)-13-(2-bromo-phenyl)parthenolide (5c) activates oocyte maturation
independently of progesterone stimulation. Compounds 5b and 5c displayed modest
growth inhibition on select cancer cell lines at 10 MUM dose when tested on the
panel of 60 cancer cell lines. By contrast, compounds (5f and 7) did not modulate
oocyte maturation but did exhibit micromolar level growth inhibition against most
of the human cancer cell lines over a range of doses. Together, our findings
indicate that screening of compounds in the oocyte maturation assay may identify
additional effective cell cycle regulatory compounds that do not necessarily
exert overt cytotoxicity as assessed in traditional drug screening assays.
PMID- 25117654
TI - Systemic lupus erythematosus-associated acute transverse myelitis:
manifestations, treatments, outcomes, and prognostic factors in 20 patients.
AB - BACKGROUND: Transverse myelitis is a rare complication of systemic lupus
erythematosus (SLE). This retrospective multicentre study identifies the
prognostic factors in a relatively large patient series. PATIENTS AND METHODS:
Twenty patients fulfilled the SLE criteria of the ACR classification and the
Transverse Myelitis Consortium Working Group. A severe neurological flare was
defined as muscle strength grade <3/5 in more than half the muscle groups at the
motor neurological level. Inability to run or another significant ambulation
unrelated disability was considered as 'unfavourable neurological outcome'.
RESULTS: Myelitis was the first SLE symptom in 12 patients; in the eight others,
it occurred 8.6 years (median delay) after SLE onset. Eleven patients presented
severe neurological impairments. The treatment included corticosteroids in all
patients associated with intravenous cyclophosphamide in 11 and/or
hydroxychloroquine in 14. Unfavourable outcomes were observed in 53% of the
patients at six months and in 28% at end of follow-up (median: 5.9 years). An
initial severe neurological impairment and no cyclophosphamide use were
associated with unfavourable neurological outcomes at six months and at end of
follow-up, respectively. CONCLUSION: Transverse myelitis may reveal SLE or occur
more than 10 years after SLE diagnosis. The initial severity of the neurological
flare (with paraplegia) is the main prognostic marker. The study provides
arguments for cyclophosphamide use.
PMID- 25117655
TI - Thrombopoietin levels in systemic lupus erythematosus are linked to inflammatory
cytokines, but unrelated to thrombocytopenia or thrombosis.
AB - BACKGROUND: Thrombopoietin (TPO) is a liver-produced protein that drives
megakaryocyte maturation. TPO regulates platelet production and can increase
platelet and endothelial reactivity. We investigated the relationship between TPO
and the occurrence of thrombocytopenia and thrombosis in patients with systemic
lupus erythematosus (SLE). METHODS: We undertook a cohort study of SLE patients
(n = 98) with clinical data collected simultaneously with sampling for TPO,
inflammatory cytokines and autoantibody detection. TPO levels were measured by
sandwich ELISA with patients with rheumatoid arthritis (RA) (n = 100) and
controls (n = 79) as comparators. Disease associations were evaluated using non
parametric methods. RESULTS: TPO levels in SLE (median 8 pg/ml, mean 326, range
8992) were moderately increased compared with RA (median 8 pg/ml, mean 100, range
1659, p = 0.07) and controls (median 8, mean 94, range 2088, p = 0.1). Among SLE
patients, TPO levels did not correlate with platelet count or levels of
antiphospholipid antibodies. The prevalence of thrombocytopenic episodes,
thrombotic events or active disease was not increased in patients with high TPO
levels. TPO levels correlated with MIP-1alpha (Rs 0.56, p < 0.001), IL6 (Rs 0.26,
p = 0.02) and IL4 (Rs 0.29, p = 0.01), and inversely correlated to C4 (Rs -0.23,
p = 0.04). MIP-1alpha was the strongest independent predictor of increased TPO
levels. CONCLUSION: TPO levels are elevated in 20% of patients, but are not
closely related to the occurrence of thrombocytopenia or thrombosis in SLE. MIP1
alpha is the main factor driving higher TPO levels among patients with SLE,
likely through its inhibitory effect on megakaryocyte function.
PMID- 25117656
TI - miRPlant: an integrated tool for identification of plant miRNA from RNA
sequencing data.
AB - BACKGROUND: Small RNA sequencing is commonly used to identify novel miRNAs and to
determine their expression levels in plants. There are several miRNA
identification tools for animals such as miRDeep, miRDeep2 and miRDeep*. miRDeep
P was developed to identify plant miRNA using miRDeep's probabilistic model of
miRNA biogenesis, but it depends on several third party tools and lacks a user
friendly interface. The objective of our miRPlant program is to predict novel
plant miRNA, while providing a user-friendly interface with improved accuracy of
prediction. RESULT: We have developed a user-friendly plant miRNA prediction tool
called miRPlant. We show using 16 plant miRNA datasets from four different plant
species that miRPlant has at least a 10% improvement in accuracy compared to
miRDeep-P, which is the most popular plant miRNA prediction tool. Furthermore,
miRPlant uses a Graphical User Interface for data input and output, and
identified miRNA are shown with all RNAseq reads in a hairpin diagram.
CONCLUSIONS: We have developed miRPlant which extends miRDeep* to various plant
species by adopting suitable strategies to identify hairpin excision regions and
hairpin structure filtering for plants. miRPlant does not require any third party
tools such as mapping or RNA secondary structure prediction tools. miRPlant is
also the first plant miRNA prediction tool that dynamically plots miRNA hairpin
structure with small reads for identified novel miRNAs. This feature will enable
biologists to visualize novel pre-miRNA structure and the location of small RNA
reads relative to the hairpin. Moreover, miRPlant can be easily used by
biologists with limited bioinformatics skills.miRPlant and its manual are freely
available at http://www.australianprostatecentre.org/research/software/mirplant
or http://sourceforge.net/projects/mirplant/.
PMID- 25117658
TI - Knuiman et al. respond to "Time-varying neighborhood environments".
PMID- 25117657
TI - Characterization of the rapid transcriptional response to long-term sensitization
training in Aplysia californica.
AB - We used a custom-designed microarray and quantitative PCR to characterize the
rapid transcriptional response to long-term sensitization training in the marine
mollusk Aplysia californica. Aplysia were exposed to repeated noxious shocks to
one side of the body, a procedure known to induce a long-lasting, transcription
dependent increase in reflex responsiveness that is restricted to the side of
training. One hour after training, pleural ganglia from the trained and untrained
sides of the body were harvested; these ganglia contain the sensory nociceptors
which help mediate the expression of long-term sensitization memory. Microarray
analysis from 8 biological replicates suggests that long-term sensitization
training rapidly regulates at least 81 transcripts. We used qPCR to test a subset
of these transcripts and found that 83% were confirmed in the same samples, and
86% of these were again confirmed in an independent sample. Thus, our new
microarray design shows strong convergent and predictive validity for analyzing
the transcriptional correlates of memory in Aplysia. Fully validated transcripts
include some previously identified as regulated in this paradigm (ApC/EBP and
ApEgr) but also include novel findings. Specifically, we show that long-term
sensitization training rapidly up-regulates the expression of transcripts which
may encode Aplysia homologs of a C/EBPgamma transcription factor, a glycine
transporter (GlyT2), and a vacuolar-protein-sorting-associated protein (VPS36).
PMID- 25117660
TI - A longitudinal analysis of the influence of the neighborhood built environment on
walking for transportation: the RESIDE study.
AB - The purpose of the present analysis was to use longitudinal data collected over 7
years (from 4 surveys) in the Residential Environments (RESIDE) Study (Perth,
Australia, 2003-2012) to more carefully examine the relationship of neighborhood
walkability and destination accessibility with walking for transportation that
has been seen in many cross-sectional studies. We compared effect estimates from
3 types of logistic regression models: 2 that utilize all available data (a
population marginal model and a subject-level mixed model) and a third subject
level conditional model that exclusively uses within-person longitudinal
evidence. The results support the evidence that neighborhood walkability
(especially land-use mix and street connectivity), local access to public transit
stops, and variety in the types of local destinations are important determinants
of walking for transportation. The similarity of subject-level effect estimates
from logistic mixed models and those from conditional logistic models indicates
that there is little or no bias from uncontrolled time-constant residential
preference (self-selection) factors; however, confounding by uncontrolled time
varying factors, such as health status, remains a possibility. These findings
provide policy makers and urban planners with further evidence that certain
features of the built environment may be important in the design of neighborhoods
to increase walking for transportation and meet the health needs of residents.
PMID- 25117659
TI - Invited commentary: Taking advantage of time-varying neighborhood environments.
AB - Neighborhood built environment characteristics may encourage physical activity,
but previous literature on the topic has been critiqued for its reliance on cross
sectional data. In this issue of the Journal, Knuiman et al. (Am J Epidemiol.
2014;180(5):453-461) present longitudinal analyses of built environment
characteristics as predictors of neighborhood transportation walking. We take
this opportunity to comment on self-selection, exposure measurement, outcome
form, analyses, and future directions. The Residential Environments (RESIDE)
Study follows individuals as they relocate into new housing. The outcome, which
is neighborhood transportation walking, has several important limitations with
regards to public health relevance, dichotomization, and potential bias. Three
estimation strategies were pursued: marginal modeling, random-effects modeling,
and fixed-effects modeling. Knuiman et al. defend fixed-effects modeling as the
one that most effectively controls for unmeasured time-invariant confounders, and
it will do so as long as confounders have a constant effect over time. Fixed
effects modeling requires no distributional assumptions regarding the
heterogeneity of subject-specific effects. Associations of time-varying
neighborhood characteristics with walking are interpreted at the subject level
for both fixed- and random-effects models. Cross-sectional data have set the
stage for the next generation of neighborhood research, which should leverage
longitudinal changes in both place and health behaviors. Careful interpretation
is warranted as longitudinal data become available for analysis.
PMID- 25117661
TI - Research for better health: the Panamanian priority-setting experience and the
need for a new process.
AB - BACKGROUND: Panama is, economically, the fastest growing country in Central
America and is making efforts to improve management mechanisms for research and
innovation. However, due to contextual factors, the Panamanian Health Research
System is not well developed and is poorly coordinated with the Health System.
Likewise, despite recent efforts to define a National Health Research Agenda,
implementing this agenda and aligning it with Panamanians' health needs remains
difficult. This articles aims to review Panama's experience in health research
priority setting by analyzing the fairness of previous prioritization processes
in order to promote an agreed-upon national agenda aligned with public health
needs. METHODS: The three health research prioritization processes performed in
Panama between 2006 and 2011 were analyzed based on the guidelines established by
the four "Accountability for Reasonableness" principles, namely "relevance",
"publicity", "revision", and "enforcement", which provide a framework for
evaluating priority-setting fairness. RESULTS: The three health research priority
setting events performed in Panama during the reference period demonstrated a
heterogeneous pattern of decision-making strategies, stakeholder group
composition, and prioritization outcomes. None of the three analyzed events
featured an open discussion process with the scientific community, health care
providers, or civil society in order to reach consensus. CONCLUSIONS: This
investigation makes evident the lack of a strategy to encourage open discussion
by the multiple stakeholders and interest groups that should be involved during
the priority-setting process. The analysis reveals the need for a new priority
setting exercise that validates the National Agenda, promotes its implementation
by the National Secretariat for Science, Technology and Innovation in conjunction
with the Ministry of Health, and empowers multiple stakeholders; such an exercise
would, in turn, favor the implementation of the agenda.
PMID- 25117663
TI - Utilization of stem cells to treat congenital heart disease: hype and hope.
AB - PURPOSE OF REVIEW: Surgical advances over the past few decades have transformed
the clinical management of congenital heart disease, such as hypoplastic left
heart syndrome. Congenital heart disease affects more than 1% of liveborn infants
and accounts for more than 2.5 million affected children per year worldwide. The
cost and availability of complex medical management for these children becomes
bluntly realized when heart failure progresses and only palliative options
remain. Cell-based cardiac regeneration has been the focus of intensive efforts
in adult heart disease for more than a decade and now has promise for pediatrics.
RECENT FINDINGS: Innate cardiac regeneration in the pediatric setting is
measurable and potentially modifiable in the early stages of development.
Repurposing cell-based manufactured products to promote cardiac regeneration in
congenital heart disease has demonstrated significant improvement in cases of
dilated cardiomyopathy and structural heart disease in infants. SUMMARY: A focus
on preemptive cardiac regeneration in the pediatric setting may offer new
insights into the timing of surgery, location of cell-based delivery, and type of
cell-based regeneration that could further inform acquired cardiac disease
applications. The concept of cell-based pediatric cardiac regenerative surgery
could transform the management of congenital heart disease when cost-effective
strategies produce a valuable adjunctive solution to improve outcomes of cardiac
surgery.
PMID- 25117662
TI - Methylthioadenosine reprograms macrophage activation through adenosine receptor
stimulation.
AB - Regulation of inflammation is necessary to balance sufficient pathogen clearance
with excessive tissue damage. Central to regulating inflammation is the switch
from a pro-inflammatory pathway to an anti-inflammatory pathway. Macrophages are
well-positioned to initiate this switch, and as such are the target of multiple
therapeutics. One such potential therapeutic is methylthioadenosine (MTA), which
inhibits TNFalpha production following LPS stimulation. We found that MTA could
block TNFalpha production by multiple TLR ligands. Further, it prevented surface
expression of CD69 and CD86 and reduced NF-KB signaling. We then determined that
the mechanism of this action by MTA is signaling through adenosine A2 receptors.
A2 receptors and TLR receptors synergized to promote an anti-inflammatory
phenotype, as MTA enhanced LPS tolerance. In contrast, IL-1beta production and
processing was not affected by MTA exposure. Taken together, these data
demonstrate that MTA reprograms TLR activation pathways via adenosine receptors
to promote resolution of inflammation.
PMID- 25117664
TI - Genetic variation in dihydropyrimidine dehydrogenase (DPYD) gene in a healthy
adult Indian population.
AB - BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) encoded by DPYD gene is the
major enzyme involved in metabolism of 5-flurouracil (5-FU), a pyrimidine
analogue used in cancer chemotherapy. Although very effective as a cancer
therapeutic drug, if not rapidly metabolized, 5-FU may prove lethal. Single
nucleotide variants (SNVs) within DPYD that modulate DPD enzyme activity
contribute to 5-FU toxicity. STUDY: This study looked for DPYD SNVs common in the
Indian population that might be associated with variable DPD activity and drug
toxicity. To achieve this, sequencing analysis was performed of all 23 exons and
flanking intronic regions of the DPYD gene in a cohort of 50 healthy adult
Indians. This study detected 22 SNVs including intronic, synonymous and non
synonymous changes in the DPYD gene, of which six have not been documented
before. Allelic frequency was calculated for the observed variants and linkage
disequilibrium (LD) analysis was performed on variants with frequency >=0.1 to
identify haplotypes. CONCLUSIONS: This study provides a brief overview of the
genetic polymorphism in DPYD in Indians and emphasizes the need for a large scale
extensive study to establish markers associated with the frequently observed
variable drug metabolism.
PMID- 25117665
TI - Infection and pathology in Queensland grouper, Epinephelus lanceolatus, (Bloch),
caused by exposure to Streptococcus agalactiae via different routes.
AB - Since 2007, 96 wild Queensland groupers, Epinephelus lanceolatus, (Bloch), have
been found dead in NE Australia. In some cases, Streptococcus agalactiae (Group B
Streptococcus, GBS) was isolated. At present, a GBS isolate from a wild grouper
case was employed in experimental challenge trials in hatchery-reared Queensland
grouper by different routes of exposure. Injection resulted in rapid development
of clinical signs including bilateral exophthalmia, hyperaemic skin or fins and
abnormal swimming. Death occurred in, and GBS was re-isolated from, 98% fish
injected and was detected by PCR in brain, head kidney and spleen from all fish,
regardless of challenge dose. Challenge by immersion resulted in lower morbidity
with a clear dose response. Whilst infection was established via oral challenge
by admixture with feed, no mortality occurred. Histology showed pathology
consistent with GBS infection in organs examined from all injected fish, from
fish challenged with medium and high doses by immersion, and from high-dose oral
challenge. These experimental challenges demonstrated that GBS isolated from wild
Queensland grouper reproduced disease in experimentally challenged fish and
resulted in pathology that was consistent with that seen in wild Queensland
grouper infected with S. agalactiae.
PMID- 25117675
TI - Silencing of microRNA-122 is an early event during hepatocarcinogenesis from non
alcoholic steatohepatitis.
AB - Non-alcoholic steatohepatitis (NASH) has emerged as a common cause of chronic
liver disease and virus-independent hepatocellular carcinoma (HCC) in patients
with obesity, diabetes, and metabolic syndrome. To reveal the molecular mechanism
underlying hepatocarcinogenesis from NASH, microRNA (miRNA) expression profiles
were analyzed in STAM mice, a NASH-HCC animal model. MicroRNA expression was also
examined in 42 clinical samples of HCC tissue. Histopathological images of the
liver of STAM mice at the ages of 6, 8, 12, and 18 weeks showed findings
compatible with fatty liver, NASH, liver cirrhosis (LC), and HCC, respectively.
Expression of miR-122 in non-tumor LC at the age of 18 weeks was significantly
lower than that in LC at the age of 12 weeks. Expression of miR-122 was further
decreased in HCCs relative to non-tumor LC at the age of 18 weeks. Expression of
miR-122 was also decreased in clinical samples of liver tissue showing
macrovesicular steatosis and HCC, being consistent with the findings in the NASH
model mice. DNA methylation analysis revealed that silencing of miR-122 was not
mediated by DNA hypermethylation of the promoter region. These results suggest
that silencing of miR-122 is an early event during hepatocarcinogenesis from
NASH, and that miR-122 could be a novel molecular marker for evaluating the risk
of HCC in patients with NASH.
PMID- 25117677
TI - Paternal factor V Leiden and recurrent pregnancy loss: a new concept behind fetal
genetics? Reply.
PMID- 25117676
TI - Sparstolonin B attenuates hypoxia-induced apoptosis, necrosis and inflammation in
cultured rat left ventricular tissue slices.
AB - PURPOSE: Ischemia/reperfusion results in tissue damage, a rapid increase in
cytokines and chemokines and inflammatory cell infiltration. Herein we
investigated the ability of a selective TLR2/4 antagonist, Sparstolonin B (SsnB),
to protect rat cultured left ventricular tissue (LV) slices from hypoxic injury
by inhibiting the myocardial inflammatory response independent of inflammatory
cell infiltration. METHODS AND RESULTS: Media Lactate dehydrogenase (LDH) levels
were measured to reflect hypoxia-induced cytotoxicity and cell injury with and
without SsnB. Incubation with SsnB (15 and 30 MUM) significantly reduced by 20
and 40%, respectively, the amount of LDH released from the hypoxic LV slices.
TUNEL staining showed that SsnB significantly attenuated the levels of hypoxia
induced apoptotic cells from 61.5 +/- 4.0 to 27.0 +/- 2.1 (15 MUM SsnB) and 23.5
+/- 2.2 (30 MUM SsnB) cells/unit area. Similarly, the Periodic Acid-Schiff (PAS)
staining of ischemic areas in untreated hypoxic LV slices was increased 17 fold
from 0.26+/- 0.09 to 4.41 +/- 0.43%, while in hypoxic slices incubated with 15
and 30 MUM of SsnB, the PAS positive ischemic areas were increased by only 6.4
fold to 1.66 +/- 0.39% and 3.8 fold to 1.00 +/- 0.22%, respectively. Rt-PCR
confirmed that MCP1 and IL-6 expression during hypoxia was elevated by 2 and 4
fold, respectively, while their up-regulation was significantly inhibited (i.e.,
< 0.7 fold increase) by SsnB. CONCLUSION: The selective TLR2/4 antagonist,
Sparstolonin B, can substantially protect LV myocardium via its ability to
inhibit injury resulting from hypoxic myocardial-generated inflammation.
Accordingly SsnB has potential as a therapeutic agent for the attenuation of
myocardial ischemia-reperfusion injury.
PMID- 25117678
TI - Closing the gap between glia and neuroblast proliferation.
AB - Reporting in this issue of Developmental Cell, Speder and Brand (2014) show that
gap junctions are required in blood-brain barrier glial cells to reactivate
proliferation of quiescent neuroblasts. Gap junctions allow synchronous Ca(2+)
waves and control insulin-like protein Dipl6 expression and secretion to trigger
neuroblast division.
PMID- 25117679
TI - A role for beta3-integrins in linking breast development and cancer.
AB - Pregnancy induces a rapid and controlled expansion of mammary stem cells. In this
issue of Developmental Cell, Desgrosellier et al. (2014) show that beta3-integrin
is required downstream of hormonal signaling and TGFbeta2 to regulate mammary
stem cell number and alveolar development specifically during early pregnancy.
PMID- 25117680
TI - From blood to brain: the neurogenic niche of the crayfish brain.
AB - Adult neurogenic niches are present in both vertebrates and invertebrates. Where
do stem cells populating these niches originate, and what are the mechanisms
maintaining their self-renewal? In this issue of Developmental Cell, Benton et
al. (2014) show that in crayfish, hemolymph-derived cells enter a neurogenic
niche to replenish neural progenitors.
PMID- 25117681
TI - Control systems of membrane transport at the interface between the endoplasmic
reticulum and the Golgi.
AB - A fundamental property of cellular processes is to maintain homeostasis despite
varying internal and external conditions. Within the membrane transport
apparatus, variations in membrane fluxes from the endoplasmic reticulum (ER) to
the Golgi complex are balanced by opposite fluxes from the Golgi to the ER to
maintain homeostasis between the two organelles. Here we describe a molecular
device that balances transport fluxes by integrating transduction cascades with
the transport machinery. Specifically, ER-to-Golgi transport activates the KDEL
receptor at the Golgi, which triggers a cascade that involves Gs and adenylyl
cyclase and phosphodiesterase isoforms and then PKA activation and results in the
phosphorylation of transport machinery proteins. This induces retrograde traffic
to the ER and balances transport fluxes between the ER and Golgi. Moreover, the
KDEL receptor activates CREB1 and other transcription factors that upregulate
transport-related genes. Thus, a Golgi-based control system maintains transport
homeostasis through both signaling and transcriptional networks.
PMID- 25117683
TI - Cells from the immune system generate adult-born neurons in crayfish.
AB - Neurogenesis is an ongoing process in the brains of adult decapod crustaceans.
However, the first-generation precursors that produce adult-born neurons, which
reside in a neurogenic niche, are not self-renewing in crayfish and must be
replenished. The source of these neuronal precursors is unknown. Here, we report
that adult-born neurons in crayfish can be derived from hemocytes. Following
adoptive transfer of 5-ethynyl-2'-deoxyuridine (EdU)-labeled hemocytes, labeled
cells populate the neurogenic niche containing the first-generation neuronal
precursors. Seven weeks after adoptive transfer, EdU-labeled cells are located in
brain clusters 9 and 10 (where adult-born neurons differentiate) and express
appropriate neurotransmitters. Moreover, the number of cells composing the
neurogenic niche in crayfish is tightly correlated with total hemocyte counts
(THCs) and can be manipulated by raising or lowering THC. These studies identify
hemocytes as a source of adult-born neurons in crayfish and demonstrate that the
immune system is a key contributor to adult neurogenesis.
PMID- 25117682
TI - Integrin alphavbeta3 drives slug activation and stemness in the pregnant and
neoplastic mammary gland.
AB - Although integrin alphavbeta3 is linked to cancer progression, its role in
epithelial development is unclear. Here, we show that alphavbeta3 plays a
critical role in adult mammary stem cells (MaSCs) during pregnancy. Whereas
alphavbeta3 is a luminal progenitor marker in the virgin gland, we noted
increased alphavbeta3 expression in MaSCs at midpregnancy. Accordingly, mice
lacking alphavbeta3 or expressing a signaling-deficient receptor showed defective
mammary gland morphogenesis during pregnancy. This was associated with decreased
MaSC expansion, clonogenicity, and expression of Slug, a master regulator of
MaSCs. Surprisingly, alphavbeta3-deficient mice displayed normal development of
the virgin gland with no effect on luminal progenitors. Transforming growth
factor beta2 (TGF-beta2) induced alphavbeta3 expression, enhancing Slug nuclear
accumulation and MaSC clonogenicity. In human breast cancer cells, alphavbeta3
was necessary and sufficient for Slug activation, tumorsphere formation, and
tumor initiation. Thus, pregnancy-associated MaSCs require a TGF
beta2/alphavbeta3/Slug pathway, which may contribute to breast cancer progression
and stemness.
PMID- 25117684
TI - CLASPs are required for proper microtubule localization of end-binding proteins.
AB - Microtubule (MT) plus-end tracking proteins (+TIPs) preferentially localize to MT
plus ends. End-binding proteins (EBs) are master regulators of the +TIP complex;
however, it is unknown whether EBs are regulated by other +TIPs. Here, we show
that cytoplasmic linker-associated proteins (CLASPs) modulate EB localization at
MTs. In CLASP-depleted cells, EBs localized along the MT lattice in addition to
plus ends. The MT-binding region of CLASP was sufficient for restoring normal EB
localization, whereas neither EB-CLASP interactions nor EB tail-binding proteins
are involved. In vitro assays revealed that CLASP directly functions to remove EB
from MTs. Importantly, this effect occurs specifically during MT polymerization,
but not at preformed MTs. Increased GTP-tubulin content within MTs in CLASP
depleted cells suggests that CLASPs facilitate GTP hydrolysis to reduce EB
lattice binding. Together, these findings suggest that CLASPs influence the MT
lattice itself to regulate EB and determine exclusive plus-end localization of
EBs in cells.
PMID- 25117685
TI - N-cadherin locks left-right asymmetry by ending the leftward movement of Hensen's
node cells.
AB - The stereotypic left-right (LR) asymmetric distribution of internal organs is due
to an asymmetric molecular cascade in the lateral plate mesoderm (LPM) that is
originated at the embryonic node. In chicken embryos, molecular asymmetries at
Hensen's node are created by leftward cell movements that occur transiently. What
terminates these movements, and, moreover, what is the impact of prolonging them
on the LR asymmetry cascade? We show that leftward movements last longer when N
cadherin function is blocked and cease prematurely when N-cadherin is
overexpressed on the right side of the node. The prolonged leftward movements
lead to loss of asymmetric expression of fgf8 and nodal at the node region. This
originates an abnormal expression of the asymmetric genes cer1 and snai1 in the
LPM, resulting in mispositioned hearts. We conclude that N-cadherin stops the
leftward cell movements and that this termination is an essential step in the
establishment of LR asymmetry.
PMID- 25117686
TI - Cisplatin-tethered gold nanospheres for multimodal chemo-radiotherapy of
glioblastoma.
AB - Glioblastoma multiforme (GBM) remains the most aggressive and challenging brain
tumour to treat. We report the first successful chemo-radiotherapy on patient
derived treatment resistant GBM cells using a cisplatin-tethered gold nanosphere.
After intracellular uptake, the nanosphere effects DNA damage which initiates
caspase-mediated apoptosis in those cells. In the presence of radiation, both
gold and platinum of cisplatin, serve as high atomic number radiosensitizers
leading to the emission of ionizing photoelectrons and Auger electrons. This
resulted in enhanced synergy between cisplatin and radiotherapy mediated
cytotoxicity, and photo/Auger electron mediated radiosensitisation leading to
complete ablation of the tumour cells in an in vitro model system. This study
demonstrates the potential of designed nanoparticles to target aggressive cancers
in the patient derived cell lines providing a platform to move towards treatment
strategies.
PMID- 25117687
TI - What would you like to eat, Mr CKD Microbiota? A Mediterranean Diet, please!
AB - In this review we elucidate the role of gut microbiota as the plausible missing
link between food and health, focusing on chronic kidney disease (CKD).
Microbiota, the microbial community harboured in the large intestine, is
considered a symbiotic "supplementary organ". It contributes to digestion, mainly
through two catabolic pathways: saccharolytic (fermentation) or proteolytic
(putrefaction). It also interacts with host influencing immunity, metabolism, and
health status. It is believed that a balanced healthy microbiota is primarily
saccharolytic and diet has a deep effect on its composition. Mediterranean Diet,
UNESCO "Intangible Cultural Heritage of Humanity", prevents cardiovascular and
metabolic systemic diseases, thanks to the high supply of fibres and
antioxidants. Mediterranean Diet also favours the prevalence of saccharolytic
species, while Western Diet promotes the shift towards a proteolytic profile
(dysbiosis). Emerging evidences highlight the association between a wide range of
diseases and dysbiosis. In CKD a vicious circle exists, in which proteolytic
derived microbial metabolites (p-cresol and indoxyl sulphate), represent the main
circulating uremic toxins: their accumulation worsens dysbiosis and promotes CKD
progression. Gut microbiota shaping through non-pharmacologic nutritional
treatments, based on Mediterranean Diet, represents an innovative approach in
CKD, potentially restoring microbiota balance, ameliorating CKD conditions and
slowing down disease progression.
PMID- 25117688
TI - State-dependent neutral delay equations from population dynamics.
AB - A novel class of state-dependent delay equations is derived from the balance laws
of age-structured population dynamics, assuming that birth rates and death rates,
as functions of age, are piece-wise constant and that the length of the juvenile
phase depends on the total adult population size. The resulting class of
equations includes also neutral delay equations. All these equations are very
different from the standard delay equations with state-dependent delay since the
balance laws require non-linear correction factors. These equations can be
written as systems for two variables consisting of an ordinary differential
equation (ODE) and a generalized shift, a form suitable for numerical
calculations. It is shown that the neutral equation (and the corresponding ODE-
shift system) is a limiting case of a system of two standard delay equations.
PMID- 25117690
TI - Radon testing in schools in New York State: a 20-year summary.
AB - For nearly 20 years the Department of Health has conducted programs to assist in
the measurement and reduction of indoor radon concentrations in 186 schools
located primarily in Zone 1 areas of New York State. Although many schools had
few or no rooms containing radon above 148 Bq/m(3), some rooms had >740 Bq/m(3)
and remediation techniques were utilized to reduce exposure. Short-term radon
measurements in the schools showed little correlation to basement and first-floor
radon results from single-family homes in the towns.
PMID- 25117689
TI - The preventive effect of atorvastatin on atrial fibrillation: a meta-analysis of
randomized controlled trials.
AB - BACKGROUND: A number of clinical and experimental studies have investigated the
effect of atorvastatin on atrial fibrillation (AF), but the results are
equivocal. This meta-analysis was performed to evaluate whether atorvastatin can
reduce the risk of AF in different populations. METHODS: We searched PubMed,
EMBASE and the Cochrane Database for all published studies that examined the
effect of atorvastatin therapy on AF up to April 2014. A random effects model was
used when there was substantial heterogeneity and a fixed effects model when
there was negligible heterogeneity. RESULTS: Eighteen published studies including
9952 patients with sinus rhythm were identified for inclusion in the analysis.
Ten studies investigated primary prevention of AF by atorvastatin in patients
without AF, seven studies investigated secondary prevention of atorvastatin in
patients with AF, and one study investigated mixed populations of patients.
Overall, atorvastatin was associated with a decreased risk of AF (odds ratio (OR)
0.51, 95% confidence interval (CI) 0.36-0.70, P < 0.0001). However, subgroup
analyses showed that in the primary prevention subgroup (OR 0.55, 95% CI 0.38
0.81, P = 0.002), atorvastatin reduced the risk of new-onset AF in patients after
coronary surgery (OR 0.44, 95% CI 0.29-0.68, P = 0.0002), but had no beneficial
effect in patients without coronary surgery (OR 0.97, 95% CI 0.59-1.58, P =
0.89); in the secondary prevention subgroup, atorvastatin had no beneficial
effect on AF recurrence in patients with electrical cardioversion (EC) (OR 0.57,
95% CI 0.25-1.32, P = 0.19) or without EC (OR 0.38, 95% CI 0.14-1.06, P = 0.06).
CONCLUSIONS: This meta-analysis suggests that atorvastatin has an overall
protective effect against AF. However, this preventive effect was not seen in all
types of AF. Atorvastatin was significantly associated with a decreased risk of
new-onset AF in patients after coronary surgery. Moreover, atorvastatin did not
prove to exert a significant protective effect against the AF recurrences in both
patients who had experienced sinus rhythm restoration by means of EC and those
who had obtained cardioversion by means of drug therapy. Thus, further
prospective studies are warranted.
PMID- 25117691
TI - Interhemispheric plasticity protects the deafferented somatosensory cortex from
functional takeover after nerve injury.
AB - Functional changes across brain hemispheres have been reported after unilateral
cortical or peripheral nerve injury. Interhemispheric callosal connections
usually underlie this cortico-cortical plasticity. However, the effect of the
altered callosal inputs on local cortical plasticity in the adult brain is not
well studied. Ipsilateral functional magnetic resonance imaging (fMRI) activation
has been reliably detected in the deafferented barrel cortex (BC) at 2 weeks
after unilateral infraorbital denervation (IO) in adult rats. The ipsilateral
fMRI signal relies on callosal-mediated interhemispheric plasticity. This form of
interhemispheric plasticity provides a good chronic model to study the
interaction between callosal inputs and local cortical plasticity. The receptive
field of forepaw in the primary somatosensory cortex (S1), which is adjacent to
the BC, was mapped with fMRI. The S1 receptive field expanded to take over a
portion of the BC in 2 weeks after both ascending inputs and callosal inputs were
removed in IO rats with ablated contralateral BC (IO+ablation). This expansion,
estimated specifically by fMRI mapping, is significantly larger than what has
been observed in the IO rats with intact callosal connectivity, as well as in the
rats with sham surgery. This work indicates that altered callosal inputs prevent
the functional takeover of the deafferented BC from adjacent cortices and may
help preserve the functional identity of the BC.
PMID- 25117692
TI - The confounded self-efficacy construct: conceptual analysis and recommendations
for future research.
AB - Self-efficacy is central to health behaviour theories due to its robust
predictive capabilities. In this paper, we present and review evidence for a self
efficacy-as-motivation argument in which standard self-efficacy questionnaires -
i.e., ratings of whether participants 'can do' the target behaviour - reflect
motivation rather than perceived capability. The potential implication is that
associations between self-efficacy ratings (particularly those that employ a 'can
do' operationalisation) and health-related behaviours simply indicate that people
are likely to do what they are motivated to do. There is some empirical evidence
for the self-efficacy-as-motivation argument, with three studies demonstrating
causal effects of outcome expectancy on subsequent self-efficacy ratings. Three
additional studies show that - consistent with the self-efficacy-as-motivation
argument - controlling for motivation by adding the phrase 'if you wanted to' to
the end of self-efficacy items decreases associations between self-efficacy
ratings and motivation. Likewise, a qualitative study using a thought-listing
procedure demonstrates that self-efficacy ratings have motivational antecedents.
The available evidence suggests that the self-efficacy-as-motivation argument is
viable, although more research is needed. Meanwhile, we recommend that
researchers look beyond self-efficacy to identify the many and diverse sources of
motivation for health-related behaviours.
PMID- 25117694
TI - Comparisons in ambulatory physical activity in children from the United Kingdom
and Belgium.
AB - AIM: This study sought to examine ambulatory physical activity levels in
adolescents from the UK and Belgium. METHODS: Following ethics approval, 2760
children (1247 boys, 1513 girls), aged 9-14 years from Belgium (n = 1614) and the
UK (n = 1146), wore a pedometer for 4 days including at least 1 weekend day. Body
mass index (BMI) was determined from height and mass. RESULTS: A 2 (gender) * 2
(country) way ANCOVA, controlling for age and BMI, revealed a significant country
by-gender interaction for steps/day (p = 0.0001). In both Belgium and the UK,
boys were more physically active than girls (both p = 0.0001), but the difference
between boys and girls was greater for Belgian than UK children. CONCLUSION:
These results suggest there are differences in the ambulatory physical activity
patterns of children in the UK and Belgium.
PMID- 25117693
TI - Structural analysis of N- and O-glycans using ZIC-HILIC/dialysis coupled to NMR
detection.
AB - Protein glycosylation, an important and complex post-translational modification
(PTM), is involved in various biological processes, including the receptor-ligand
and cell-cell interaction, and plays a crucial role in many biological functions.
However, little is known about the glycan structures of important biological
complex samples, and the conventional glycan enrichment strategy (i.e., size
exclusion column [SEC] separation) prior to nuclear magnetic resonance (NMR)
detection is time-consuming and tedious. In this study, we developed a glycan
enrichment strategy that couples Zwitterionic hydrophilic interaction liquid
chromatography (ZIC-HILIC) with dialysis to enrich the glycans from the pronase E
digests of RNase B, followed by NMR analysis of the glycoconjugate. Our results
suggest that the ZIC-HILIC enrichment coupled with dialysis is a simple, fast,
and efficient sample preparation approach. The approach was thus applied to
analysis of a biological complex sample, the pronase E digest of the secreted
proteins from the fungus Aspergillus niger. The NMR spectra revealed that the
secreted proteins from A. niger contain both N-linked glycans with a high-mannose
core similar to the structure of the glycan from RNase B, and O-linked glycans
bearing mannose and glucose with 1->3 and 1->6 linkages. In all, our study
provides compelling evidence that ZIC-HILIC separation coupled with dialysis is
very effective and accessible in preparing glycans for the downstream NMR
analysis, which could greatly facilitate the future NMR-based glycoproteomics
research.
PMID- 25117695
TI - Detection of Japanese eel endothelial cells-infecting virus (JEECV) in the
Japanese eel Anguilla japonica (Temminck & Schlegel), living in natural habitats.
PMID- 25117696
TI - Biometry of anterior segment of human eye on both horizontal and vertical
meridians during accommodation imaged with extended scan depth optical coherence
tomography.
AB - PURPOSE: To determine the biometry of anterior segment dimensions of the human
eye on both horizontal and vertical meridians with extended scan depth optical
coherence tomography (OCT) during accommodation. METHODS: Twenty pre-presbyopic
volunteers, aged between 24 and 30, were recruited. The ocular anterior segment
of each subject was imaged using an extended scan depth OCT under non- and 3.0
diopters (D) of accommodative demands on both horizontal and vertical meridians.
All the images were analyzed to yield the following parameters: pupil diameter
(PD), anterior chamber depth (ACD), anterior and posterior surface curvatures of
the crystalline lens (ASC and PSC) and the lens thickness (LT). Two consecutive
measurements were performed to assess the repeatability and reproducibility of
this OCT. They were evaluated by calculating the within-subject standard
deviation (SD), a paired t-test, intra-class correlation coefficients (ICC) and
the coefficient of repeatability/reproducibility (CoR). RESULTS: There were no
significant differences between two consecutive measurements on either horizontal
or vertical meridians under both two different accommodative statuses (P>0.05).
The ICC for all parameters ranged from 0.775 to 0.998, except for the PSC (0.550)
on the horizontal meridian under the non-accommodative status. In addition, the
CoR for most of the parameters were excellent (0.004% to 4.89%). In all the
parameters, only PD and PSC were found different between the horizontal and
vertical meridians under both accommodative statuses (P<0.05). PD, ACD, ASC and
PSC under accommodative status were significantly smaller than those under the
non-accommodative status, except that the PSC at the vertical meridian did not
change. In addition, LT was significantly increased when accommodation.
CONCLUSION: The extended scan depth OCT successfully measured the dimensions of
the anterior eye during accommodation with good repeatability and reproducibility
on both horizontal and vertical meridians. The asymmetry of lens posterior
surface and oval-shaped pupil were found during accommodation.
PMID- 25117702
TI - In vivo subcellular imaging of tumors in mouse models using a fluorophore
conjugated anti-carcinoembryonic antigen antibody in two-photon excitation
microscopy.
AB - Recently, there has been growing interest in applying fluorescence imaging
techniques to the study of various disease processes and complex biological
phenomena in vivo. To apply these methods to clinical settings, several groups
have developed protocols for fluorescence imaging using antibodies against tumor
markers conjugated to fluorescent substances. Although these probes have been
useful in macroscopic imaging, the specificity and sensitivity of these methods
must be improved to enable them to detect micro-lesions in the early phases of
cancer, resulting in better treatment outcomes. To establish a sensitive and
highly specific imaging method, we used a fluorophore-conjugated anti
carcinoembryonic antigen (CEA) antibody to perform macroscopic and microscopic in
vivo imaging of inoculated cancer cells expressing GFP with or without CEA.
Macroscopic imaging by fluorescence zoom microscopy revealed that bio-conjugation
of Alexa Fluor 594 to the anti-CEA antibody allowed visualization of tumor mass
consisting of CEA-expressing human cancer cells, but the background levels were
unacceptably high. In contrast, microscopic imaging using a two-photon excitation
microscope and the same fluorescent antibody resulted in subcellular-resolution
imaging that was more specific and sensitive than conventional imaging using a
fluorescence zoom microscope. These results suggest that two-photon excitation
microscopy in conjunction with fluorophore-conjugated antibodies could be widely
adapted to detection of cancer-specific cell-surface molecules, both in cancer
research and in clinical applications.
PMID- 25117704
TI - Polo-like kinase 4 inhibition: a strategy for cancer therapy?
AB - In this issue of Cancer Cell, Mason and colleagues describe the development of a
Polo-like kinase 4 (PLK4) inhibitor (CFI-400945), with promising activity against
tumors formed in mice from patient-derived tumor tissue. A clinical trial has
been initiated, but questions remain as to whether PLK4 is the only relevant
therapeutic target.
PMID- 25117703
TI - Dietary squalene increases high density lipoprotein-cholesterol and paraoxonase 1
and decreases oxidative stress in mice.
AB - BACKGROUND AND PURPOSE: Squalene, the main hydrocarbon in the unsaponifiable
fraction of virgin olive oil, is involved in cholesterol synthesis and it has
been reported to own antiatherosclerotic and antiesteatosic effects. However, the
squalene's role on lipid plasma parameters and the influence of genotype on this
effect need to be addressed. EXPERIMENTAL APPROACHES: Three male mouse models
(wild-type, Apoa1- and Apoe- deficient) were fed chow semisynthetic diets
enriched in squalene to provide a dose of 1 g/kg during 11 weeks. After this
period, their plasma parameters and lipoprotein profiles were analyzed. KEY
RESULTS: Squalene administration at a dose of 1 g/kg showed decreased reactive
oxygen species in lipoprotein fractions independently of the animal background
and caused an specific increase in high density lipoprotein (HDL)-cholesterol
levels, accompanied by an increase in phosphatidylcholine and paraoxonase 1 and
no changes in apolipoproteins A1 and A4 in wild-type mice. In these mice, the
cholesterol increase was due to its esterified form and associated with an
increased hepatic expression of Lcat. These effects were not observed in absence
of apolipoprotein A1. The increases in HDL- paraoxonase 1 were translated into
decreased plasma malondialdehyde levels depending on the presence of
Apolipoprotein A1. CONCLUSIONS AND IMPLICATIONS: Dietary squalene promotes
changes in HDL- cholesterol and paraoxonase 1 and decreases reactive oxygen
species in lipoproteins and plasma malondialdehyde levels, providing new benefits
of its intake that might contribute to explain the properties of virgin olive
oil, although the phenotype related to apolipoproteins A1 and E may be
particularly relevant.
PMID- 25117705
TI - YAPping about differentiation therapy in muscle cancer.
AB - Overcoming a presumed differentiation block in the childhood muscle cancer
embryonal rhabdomyosarcoma is often thought to hold promise as an approach to
replace cytotoxic chemotherapy with molecularly-targeted differentiation
therapies. In this issue of Cancer Cell, Tremblay and colleagues implicate YAP1
and the Hippo signaling pathway in the maintenance of differentiation-arrested
and proliferative phenotypes for embryonal rhabdomyosarcoma.
PMID- 25117706
TI - RESICstance is futile-but not in glioblastoma.
AB - Genomic alterations that occur early in tumorigenesis represent fundamental diver
lesions and are perhaps of highest priority as a means to intervene
therapeutically. In this issue of Cancer Cell, Ozawa and colleagues apply an
algorithm to identify early events in glioblastoma and validate their findings in
a rigorous manner.
PMID- 25117707
TI - Inhibit globally, act locally: CDK7 inhibitors in cancer therapy.
AB - Cyclin-dependent kinases (CDKs) are involved in temporal control of the cell
cycle and transcription and play central roles in cancer development and
metastasis. Recently, Kwiatkowski and colleagues identified a novel CDK7-specific
inhibitor, THZ1, that hinders proliferation in cancer cell lines and dampens
global transcription in T cell leukemia.
PMID- 25117708
TI - When deletions gain functions: commandeering epigenetic mechanisms.
AB - Recurrent chromosomal deletions in cancer are typically thought to harbor tumor
suppressors. In a recent publication in Nature, Northcott and colleagues identify
a novel region of structural variation in medulloblastoma that leads to oncogenic
activation of GFI1B and GFI1 by repositioning these genes next to super
enhancers.
PMID- 25117709
TI - Tumor vessel normalization by chloroquine independent of autophagy.
AB - Chloroquine (CQ) has been evaluated as an autophagy blocker for cancer treatment,
but it is unknown if it acts solely by inhibiting cancer cell autophagy. We
report that CQ reduced tumor growth but improved the tumor milieu. By normalizing
tumor vessel structure and function and increasing perfusion, CQ reduced hypoxia,
cancer cell invasion, and metastasis, while improving chemotherapy delivery and
response. Inhibiting autophagy in cancer cells or endothelial cells (ECs) failed
to induce such effects. CQ's vessel normalization activity relied mainly on
alterations of endosomal Notch1 trafficking and signaling in ECs and was
abrogated by Notch1 deletion in ECs in vivo. Thus, autophagy-independent vessel
normalization by CQ restrains tumor invasion and metastasis while improving
chemotherapy, supporting the use of CQ for anticancer treatment.
PMID- 25117710
TI - Phosphorylation of ETS1 by Src family kinases prevents its recognition by the
COP1 tumor suppressor.
AB - Oncoproteins and tumor suppressors antagonistically converge on critical nodes
governing neoplastic growth, invasion, and metastasis. We discovered that
phosphorylation of the ETS1 and ETS2 transcriptional oncoproteins at specific
serine or threonine residues creates binding sites for the COP1 tumor suppressor
protein, which is an ubiquitin ligase component, leading to their destruction. In
the case of ETS1, however, phosphorylation of a neighboring tyrosine residue by
Src family kinases disrupts COP1 binding, thereby stabilizing ETS1. Src-dependent
accumulation of ETS1 in breast cancer cells promotes anchorage-independent growth
in vitro and tumor growth in vivo. These findings expand the list of potential
COP1 substrates to include proteins whose COP1-binding sites are subject to
regulatory phosphorylation and provide insights into transformation by Src family
kinases.
PMID- 25117711
TI - Regulation of p53 by Mdm2 E3 ligase function is dispensable in embryogenesis and
development, but essential in response to DNA damage.
AB - Mdm2 E3 ubiquitin ligase-mediated p53 degradation is generally accepted as the
major mechanism for p53 regulation; nevertheless, the in vivo significance of
this function has not been unequivocally established. Here, we have generated an
Mdm2(Y487A) knockin mouse; Mdm2(Y487A) mutation inactivates Mdm2 E3 ligase
function without affecting its ability to bind its homolog MdmX. Unexpectedly,
Mdm2(Y487A/Y487A) mice were viable and developed normally into adulthood. While
disruption of Mdm2 E3 ligase function resulted in p53 accumulation, p53
transcriptional activity remained low; however, exposure to sublethal stress
resulted in hyperactive p53 and p53-dependent mortality in Mdm2(Y487A/Y487A)
mice. These findings reveal a potentially dispensable nature for Mdm2 E3 ligase
function in p53 regulation, providing insight that may affect how this pathway is
targeted therapeutically.
PMID- 25117712
TI - Lin28b is sufficient to drive liver cancer and necessary for its maintenance in
murine models.
AB - Lin28a/b are RNA-binding proteins that influence stem cell maintenance,
metabolism, and oncogenesis. Poorly differentiated, aggressive cancers often
overexpress Lin28, but its role in tumor initiation or maintenance has not been
definitively addressed. We report that LIN28B overexpression is sufficient to
initiate hepatoblastoma and hepatocellular carcinoma in murine models. We also
detected Lin28b overexpression in MYC-driven hepatoblastomas, and liver-specific
deletion of Lin28a/b reduced tumor burden, extended latency, and prolonged
survival. Both intravenous siRNA against Lin28b and conditional Lin28b deletion
reduced tumor burden and prolonged survival. Igf2bp proteins are upregulated, and
Igf2bp3 is required in the context of LIN28B overexpression to promote growth.
Therefore, multiple murine models demonstrate that Lin28b is both sufficient to
initiate liver cancer and necessary for its maintenance.
PMID- 25117715
TI - Ethylenediamine-mediated synthesis of Mn3O4 nano-octahedrons and their
performance as electrocatalysts for the oxygen evolution reaction.
AB - Mn3O4 octahedrons with well-defined facets exhibit enhanced catalytic activity
and sensing characteristics, and have attracted considerable attention in recent
years. However, current fabrication methods for Mn3O4 octahedrons generally
produce particles of micron and sub-micron sizes, and impurities such as MnO2 and
Mn2O3 are often found. We present the synthesis of Mn3O4 nano-octahedrons with a
pure Mn3O4 phase and size down to 50 nm based on a hydrothermal method using
Mn(NO3)2 as the manganese source and ethylenediamine (EDA) as the structure
mediating agent. It is found that EDA plays a crucial role in the formation of
Mn3O4 nano-octahedrons in regulating both the morphology and the crystal
structure of the products. The growth process is proposed to follow a
"dissolution-recrystallization" and "capping-molecule assisted growth" mechanism.
As electrocatalysts towards the oxygen evolution reaction, the 50 nm Mn3O4 nano
octahedrons demonstrate a considerably enhanced activity compared to 160 nm Mn3O4
octahedrons.
PMID- 25117713
TI - MYC through miR-17-92 suppresses specific target genes to maintain survival,
autonomous proliferation, and a neoplastic state.
AB - The MYC oncogene regulates gene expression through multiple mechanisms, and its
overexpression culminates in tumorigenesis. MYC inactivation reverses
turmorigenesis through the loss of distinguishing features of cancer, including
autonomous proliferation and survival. Here we report that MYC via miR-17-92
maintains a neoplastic state through the suppression of chromatin regulatory
genes Sin3b, Hbp1, Suv420h1, and Btg1, as well as the apoptosis regulator Bim.
The enforced expression of miR-17-92 prevents MYC suppression from inducing
proliferative arrest, senescence, and apoptosis and abrogates sustained tumor
regression. Knockdown of the five miR-17-92 target genes blocks senescence and
apoptosis while it modestly delays proliferative arrest, thus partially
recapitulating miR-17-92 function. We conclude that MYC, via miR-17-92, maintains
a neoplastic state by suppressing specific target genes.
PMID- 25117714
TI - Most human non-GCIMP glioblastoma subtypes evolve from a common proneural-like
precursor glioma.
AB - To understand the relationships between the non-GCIMP glioblastoma (GBM)
subgroups, we performed mathematical modeling to predict the temporal sequence of
driver events during tumorigenesis. The most common order of evolutionary events
is 1) chromosome (chr) 7 gain and chr10 loss, followed by 2) CDKN2A loss and/or
TP53 mutation, and 3) alterations canonical for specific subtypes. We then
developed a computational methodology to identify drivers of broad copy number
changes, identifying PDGFA (chr7) and PTEN (chr10) as driving initial
nondisjunction events. These predictions were validated using mouse modeling,
showing that PDGFA is sufficient to induce proneural-like gliomas and that
additional NF1 loss converts proneural to the mesenchymal subtype. Our findings
suggest that most non-GCIMP mesenchymal GBMs arise as, and evolve from, a
proneural-like precursor.
PMID- 25117716
TI - Transcriptional analysis of Volvox photoreceptors suggests the existence of
different cell-type specific light-signaling pathways.
AB - Photosynthetic organisms, e.g., plants including green algae, use a sophisticated
light-sensing system, composed of primary photoreceptors and additional
downstream signaling components, to monitor changes in the ambient light
environment towards adjust their growth and development. Although a variety of
cellular processes, e.g., initiation of cleavage division and final cellular
differentiation, have been shown to be light-regulated in the green alga Volvox
carteri, little is known about the underlying light perception and signaling
pathways. This multicellular alga possesses at least 12 photoreceptors, i.e., one
phototropin (VcPhot), four cryptochromes (VcCRYa, VcCRYp, VcCRYd1, and VcCRYd2),
and seven members of rhodopsin-like photoreceptors (VR1, VChR1, VChR2, VcHKR1,
VcHKR2, VcHKR3, and VcHKR4), which display distinct light-dependent chemical
processes based on their protein architectures and associated chromophores. Gene
expression analyses could show that the transcript levels of some of the
photoreceptor genes (e.g., VChR1 and VcHKR1) accumulate during division
cleavages, while others (e.g., VcCRYa, VcCRYp, and VcPhot) accumulate during
final cellular differentiation. However, the pattern of transcript accumulation
changes when the alga switches to the sexual development. Eight photoreceptor
genes, e.g., VcPhot, VcCRYp, and VcHKR1, are highly expressed in the somatic
cells, while only the animal-type rhodopsin VR1 was found to be highly expressed
in the reproductive cells/embryos during both asexual and sexual life cycles.
Moreover, accumulation of VChR1 and VcCRYa transcripts is more sensitive to light
and changes in response to more than one light quality. Obviously, different
regulatory mechanisms underlying gene expression control transcript accumulation
of photoreceptors not only during development, but also in a cell-type specific
way and in response to various external signals such as light quality. The
transcriptional patterns described in this study show that Volvox photoreceptors
are mostly expressed in a cell-type specific manner. This gives reason to believe
that cell-type specific light-signaling pathways allow differential regulation of
cellular and developmental processes in response to the environmental light cues.
PMID- 25117718
TI - Salt restriction in chronic kidney disease: a simple need or a must?
AB - Dietary salt restriction is one of the most important non pharmacological
intervention in the management of hypertension and cardiovascular complications.
In Chronic Kidney Disease (CKD) patients, observational and recent interventional
studies investigating the relationship between sodium intake and renal outcomes
suggest that low salt diet is warranted in this high risk category of patients.
Moreover reducing and maintaining a low salt intake in these patients plays a
fundamental role for maximizing the beneficial effect of ACE inhibitors on CKD
progression. On the other hand, in hypertensive patients there is experimental
evidence indicating that a very low sodium diet (<50 mEq/day) generates a pro
inflammatory phenotype characterized by an increase in Procalcitonin and TNF
alpha and a reduction in an anti-inflammatory cytokine like Adiponectin. In this
brief review the main mechanisms whereby salt intake may determine kidney damage
and studies showing that salt restriction may have a beneficial effect in CKD
patients will be discussed.
PMID- 25117720
TI - Late-onset cauda equina contrast enhancement: a rare magnetic resonance imaging
finding in subacute spinal cord infarction.
PMID- 25117719
TI - The effect of women's property rights on HIV: a search for quantitative evidence.
AB - In recent years, efforts to reduce HIV transmission have begun to incorporate a
structural interventions approach, whereby the social, political, and economic
environment in which people live is considered an important determinant of
individual behaviors. This approach to HIV prevention is reflected in the growing
number of programs designed to address insecure or nonexistent property rights
for women living in developing countries. Qualitative and anecdotal evidence
suggests that property ownership may allow women to mitigate social, economic,
and biological effects of HIV for themselves and others through increased food
security and income generation. Even so, the relationship between women's
property and inheritance rights (WPIR) and HIV transmission behaviors is not well
understood. We explored sources of data that could be used to establish
quantitative links between WPIR and HIV. Our search for quantitative evidence
included (1) a review of peer-reviewed and "gray" literature reporting on
quantitative associations between WPIR and HIV, (2) identification and assessment
of existing data-sets for their utility in exploring this relationship, and (3)
interviews with organizations addressing women's property rights in Kenya and
Uganda about the data they collect. We found no quantitative studies linking
insecure WPIR to HIV transmission behaviors. Data-sets with relevant variables
were scarce, and those with both WPIR and HIV variables could only provide
superficial evidence of associations. Organizations addressing WPIR in Kenya and
Uganda did not collect data that could shed light on the connection between WPIR
and HIV, but the two had data and community networks that could provide a good
foundation for a future study that would include the collection of additional
information. Collaboration between groups addressing WPIR and HIV transmission
could provide the quantitative evidence needed to determine whether and how a
WPIR structural intervention could decrease HIV transmission.
PMID- 25117717
TI - Advanced biliary tract carcinomas: a retrospective multicenter analysis of first
and second-line chemotherapy.
AB - BACKGROUND: Gemcitabine/Cisplatin (Gem/CDDP) combination has demonstrated a clear
survival advantage over gemcitabine alone and has become a new standard in
advanced Biliary Tract Carcinoma (aBTC). However, Gemcitabine/Oxaliplatin (GEMOX)
combination and Gemcitabine/Carboplatin (Gem/Carb) combination regimens have
shown efficacy in phase II trials and there is no comparative study between
different platinum salts.We assessed the efficacy and safety of different
platinum-based chemotherapies at first line in aBTC patients. We also analysed
the second-line chemotherapy. METHODS: Sixty-four consecutive patients with aBTC
diagnosed between 1998 and 2010 were included for analysis. At first line
chemotherapy, 44 patients received one day GEMOX regimen (gemcitabine 1000 mg/m2
and oxaliplatin 100 mg/m2 Day 1, every 2 weeks), and 20 patients received
Gem/Carb regimen (gemcitabine at 1000 mg/m2 Days 1 and 8 with carboplatin
delivered according to an area-under-the-curve (AUC) 5 at day 1, every 3 weeks).
At second line, a total of 16 patients received a fluoropyrimidine-based
chemotherapy. RESULTS: With GEMOX regimen, median progression-free survival (PFS)
was 3.7 months (95%CI, 2.4 to 5) and median overall survival (OS) was 10.5 months
(95%CI, 6.4 to14.7). The main toxicity was peripheral neuropathy (20% grade 2 and
7% grade 3). Grade 3/4 haematological toxicities were rare.With Gem/Carb regimen,
PFS was 2.5 months (95%CI, 2.1 to 3.7) and OS was 4.8 months (95%CI, 3.7 to 5.8).
The main grade 3/4 toxicities were haematological: anaemia (45%),
thrombocytopenia (45%), and neutropenia (40%).At second-line, fluoropyrimidine
based chemotherapy was feasible in only a fourth of the patients. The median OS
was 5.3 months (95%CI, 4.1 to 6.6), and median PFS was 4.0 months (95%CI, 2.6 to
5.5). CONCLUSIONS: One day GEMOX regimen has a favourable toxicity profile and
could be an alternative to standard Gem/CDDP regimen, in particular in unfit
patients for CDDP.At second-line, selective patients may benefit from
fluoropyrimidine-based chemotherapy.
PMID- 25117721
TI - Lumbosacral discitis-osteomyelitis after mesh abdominosacrocolpopexy.
PMID- 25117722
TI - Temporal specificity of training: intra-day effects on biochemical responses and
Olympic-Weightlifting performances.
AB - The aim of this study was to investigate the performance of an Olympic
Weightlifting session training at three times of the day on the performance
related to biochemical responses. Nine weightlifters (21 +/- 0.5 years)
performed, in randomised order, on three Olympic-Weightlifting training (snatch,
clean and jerk) sessions (08:00 a.m., 02:00 p. m., 06:00 p. m.). Blood samples
were collected: before, 3 min and 48 h after each training session.
Haematological parameters and markers of muscle injury were assessed. Resting
oral temperature and rating of perceived exertion (RPE) were also assessed during
each session. ANOVA showed that the performance was better (P < 0.001) at 02:00
p. m. with a less RPE (P < 0.01) compared to the morning and the evening sessions
while there was higher (P < 0.05) oral temperature at 06:00 p. m. versus 08:00
a.m. and 02:00 p. m. Muscle damage changed immediately (without significant
effect after 48 h) after the training sessions with lower values in the evening
compared to the morning. In conclusion, the afternoon training is more effective
than morning or evening sessions for weightlifters. Therefore, coaches and
weightlifters should be advised to schedule their training session in the
afternoon hour.
PMID- 25117723
TI - The relationship between hospital volume and mortality in severe sepsis.
AB - RATIONALE: Severe sepsis is increasing in incidence and has a high rate of
inpatient mortality. Hospitals that treat a larger number of patients with severe
sepsis may offer a survival advantage. OBJECTIVES: We sought to assess the effect
of severe sepsis case volume on mortality, hypothesizing that higher volume
centers would have lower rates of inpatient death. METHODS: We performed a
retrospective cohort study over a 7-year period (2004-2010), using a nationally
representative sample of hospital admissions, examining the relation between
volume, urban location, organ dysfunction, and survival. MEASUREMENTS AND MAIN
RESULTS: To identify potential differences in outcomes, hospitals were divided
into five categories (<50, 50-99, 100-249, 250-499, and 500+ annual cases) and
adjusted mortality was compared by volume. A total of 914,200 patients with
severe sepsis were identified over a 7-year period (2004-2010). Overall in
hospital mortality was 28.1%. In a fully adjusted model, there was an inverse
relationship between severe sepsis case volume and inpatient mortality. Hospitals
in the highest volume category had substantially improved survival compared with
hospitals with the lowest case volume (adjusted odds ratio, 0.64; 95% confidence
interval, 0.60-0.69). In cases of severe sepsis with one reported organ
dysfunction, a mortality of 18.9% was found in hospitals with fewer than 50
annual cases compared with 10.4% in hospitals treating 500+ cases (adjusted odds
ratio, 0.54; 95% confidence interval, 0.49-0.59). Similar differences were found
in patients with up to three total organ dysfunctions. CONCLUSIONS: Patients with
severe sepsis treated in hospitals with higher case volumes had improved adjusted
outcomes.
PMID- 25117724
TI - Early effects of human papillomavirus vaccination in Belgium.
AB - Human papillomavirus (HPV) vaccination has been reimbursed in Belgium since 2007
for girls (12-15 years), extended to girls up to 18 years in 2008. This study
assesses the trend of HPV 16/18 infections in women less than 25 years of age
participating in opportunistic cervical cancer screening. A significant reduction
in the prevalence of HPV 16 [relative risk (RR)=0.61, 95% confidence
interval=0.39-0.95] and a nonsignificant reduction in HPV 18 (RR=0.65, 95%
confidence interval=0.29-1.48) was found in the youngest group (15-19 years). The
prevalences in the older age group did not change significantly. These findings
show the early effects of HPV vaccination and confirm the effectiveness of
immunization in a real-life setting.
PMID- 25117725
TI - Nonlinear dose-response relationship between radon exposure and the risk of lung
cancer: evidence from a meta-analysis of published observational studies.
AB - Although radon exposure (RE) has been confirmed to increase the risk of lung
cancer (LC), questions remain about the shape of the dose-response relationship
between RE and the risk of LC. We carried out a dose-response meta-analysis to
investigate and quantify the potential dose-response association between
residential and occupational exposure to radon and the risk of LC. All cohort and
case-control studies published in English and Chinese on Embase, PubMed, and
China National Knowledge Infrastructure (CNKI) digital databases through November
2013 were identified systematically. We extracted effect measures (relative risk,
odds ratio, standardized mortality ratio, standardized incidence ratio, or
standardized rate ratio) from individual studies to generate pooled results using
meta-analysis approaches. We derived meta-analytic estimates using random-effects
models taking into account the correlation between estimates. Restricted cubic
splines and generalized least-squares regression methods were used to model a
potential curvilinear relationship and to carry out a dose-response meta
analysis. Stratified analysis, sensitivity analysis, and assessment of bias were
performed in our meta-analysis. Sixty publications fulfilling the inclusion
criteria for this meta-analysis were finally included. Occupational RE was
associated with LC [risk ratio 1.86, 95% confidence interval (CI)=1.67-2.09;
I2=92.2%; 27 prospective studies], for pooled risk estimate of the: standardized
mortality ratio [2.00 (95% CI=1.82-2.32)]; standardized incidence ratio [1.45
(95% CI=1.20-1.74)]; relative risk [2.10 (95% CI=1.64-2.69)]. In a subgroup
analysis of uranium miners and residents exposed to occupational uranium, the
summary risk was 2.23 (95% CI=1.86-2.68) and 1.23 (95% CI=1.05-1.44). The overall
meta-analysis showed evidence of a nonlinear association between RE and the risk
of LC (P(nonlinearity)<0.014); in addition, the point value of residential radon
also improved the results quantitatively, where odds ratios were 1.11 (95%
CI=1.07-1.15) and 1.21 (95% CI=1.14-1.29) when the radon concentration was at the
point of 100 and 200 Bq/m3 compared with the lowest. For 17 prospective studies
with at least three categories of occupational cumulative radon dose, the dose
risk model estimated a risk ratio of 1.26 (95% CI=1.21-1.30) for 100 working
level months and 1.51 (95% CI=1.38-1.65) for 200 working level months,
respectively. The assessment of risk of bias within individual studies and across
studies indicated risk that was unlikely to alter these results markedly. This
meta-analysis shows a nonlinear dose-response association between environmental
RE and the risk of LC. This increased risk is particularly apparent when the
cumulative exposure to radon is well beyond that resulting from exposure to the
recommended limit concentration for a prolonged period of time.
PMID- 25117726
TI - Does decreased meniscal thickness affect surgical outcomes after medial
meniscectomy?
AB - BACKGROUND: There have been no clinical studies regarding the effect of decreased
meniscal thickness on outcomes after meniscectomy. PURPOSE: To examine the
postoperative outcomes of partial meniscectomy with or without horizontal
resection compared with the outcomes of subtotal meniscectomy and to evaluate the
influence of decreased thickness of the medial meniscus on outcomes after partial
meniscectomy. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total
of 312 patients who underwent medial meniscectomy were retrospectively reviewed.
Patients were divided into 3 groups: group A (n = 84) included patients with
partial meniscectomy with vertical resection, group B (n = 140) consisted of
those with partial meniscectomy with horizontal resection, and group C (n = 88)
included those with subtotal meniscectomy. Clinical function was evaluated by use
of the Lysholm knee scoring scale, International Knee Documentation Committee
(IKDC) subjective knee evaluation form, and Tapper and Hoover grading system.
Radiologic evaluation was performed with the IKDC radiographic assessment scale
as well as with measurements of the medial compartment height at the tibiofemoral
joint. Preoperative values and postoperative values measured 5 years after
operation were assessed. RESULTS: Functional outcomes in group C were inferior to
those in groups A and B according to the Lysholm knee score (mean +/- SD for
group A = 96.1 +/- 4.7, group B = 94.9 +/- 5.2, group C = 84.8 +/- 11.4; P <
.001), IKDC subjective score (group A = 92.1 +/- 6.5, group B = 91.3 +/- 8.8,
group C = 81 +/- 11.4; P < .001), and Tapper and Hoover grading system (P =
.003). There was no significant difference in scores between groups A and B. With
regard to radiologic evaluation, the IKDC radiographic grade for group C was
worse than the grades for groups A and B (P < .001); there was no significant
difference between groups A and B. However, the postoperative joint space on the
affected side was higher for group A (4.7 +/- 0.6 mm) than for groups B (4.3 +/-
0.5 mm; P < .001) and C (3.7 +/- 0.8 mm; P < .001). The joint space was higher in
group B than in group C (P < .001). CONCLUSION: Despite joint space narrowing,
decreases in meniscal thickness after partial meniscectomy for horizontal tear
had no additional adverse effect on 5-year functional and radiographic outcomes
compared with conventional partial meniscectomy preserving whole meniscal
thickness. In treating horizontal tears of the meniscus, partial meniscectomy
with complete resection of the unstable leaf was an effective method in a 5-year
follow-up study.
PMID- 25117727
TI - Three-dimensional analysis of acromial morphologic characteristics in patients
with and without rotator cuff tears using a reconstructed computed tomography
model.
AB - BACKGROUND: The relationship between rotator cuff tears and acromial shape has
yet to be clarified. As a result, the most suitable location for acromioplasty
for the treatment of rotator cuff tears is not known. PURPOSE: To determine
whether any particular change in acromial shape is significantly associated with
the presence of rotator cuff tears. STUDY DESIGN: Cross-sectional study; Level of
evidence, 3. METHODS: From 2007 to 2010, we examined 25 consecutive patients with
unilateral full-thickness rotator cuff tears who underwent arthroscopic repair
and 17 consecutive patients with adhesive capsulitis but intact rotator cuffs who
underwent arthroscopic capsular release. Before surgery, a reconstructed 3
dimensional computed tomography model was used to evaluate the acromial
structure. Changes in the shape of the affected scapula were qualitatively
evaluated relative to the unaffected, contralateral scapula by use of proximity
mapping. Differences in acromial structure between affected and unaffected
shoulders were assessed at the anterior, lateral, and medial edges and the
inferior surface. The association between rotator cuff tear size and change in
acromial structure was also evaluated. RESULTS: Rates of bony projection at the
anterior (>2 mm) and lateral (>3 mm) edges of the acromion in patients with
rotator cuff tears were significantly greater compared with rates in patients
without rotator cuff tears (P < .01). Tear size was not correlated with changes
in acromial structure (P = .37-.73). CONCLUSION: Bone spurs at the anterior and
lateral edges of the acromion are associated with the presence of full-thickness
rotator cuff tears in symptomatic patients.
PMID- 25117728
TI - The arthroscopic latarjet procedure for anterior shoulder instability: 5-year
minimum follow-up.
AB - BACKGROUND: The arthroscopic Latarjet procedure combines the benefits of
arthroscopic surgery with the low rate of recurrent instability associated with
the Latarjet procedure. Only short-term outcomes after arthroscopic Latarjet
procedure have been reported. PURPOSE: To evaluate the rate of recurrent
instability and patient outcomes a minimum of 5 years after stabilization
performed with the arthroscopic Latarjet procedure. STUDY DESIGN: Case series;
Level of evidence, 4. METHODS: Patients who underwent the arthroscopic Latarjet
procedure before June 2008 completed a questionnaire to determine whether they
had experienced a dislocation, subluxation, or further surgery. The patients also
completed the Western Ontario Shoulder Instability Index (WOSI). RESULTS: A total
of 62 of 87 patients (64/89 shoulders) were contacted for follow-up. Mean follow
up time was 76.4 months (range, 61.2-100.7 months). No patients had reported a
dislocation since their surgery. One patient reported having subluxations since
the surgery. Thus, 1 patient (1.59%) had recurrent instability after the
procedure. The mean +/- standard deviation aggregate WOSI score was 90.6% +/-
9.4%. Mean WOSI domain scores were as follows: Physical Symptoms, 90.1% +/- 8.7%;
Sports/Recreation/Work, 90.3% +/- 12.9%; Lifestyle, 93.7% +/- 9.8%; and Emotions,
88.7% +/- 17.3%. CONCLUSION: The rate of recurrent instability after arthroscopic
Latarjet procedure is low in this series of patients with a minimum 5-year follow
up. Patient outcomes as measured by the WOSI are good.
PMID- 25117729
TI - Phase II study of FOLFIRINOX for chemotherapy-naive Japanese patients with
metastatic pancreatic cancer.
AB - The FOLFIRINOX combination of chemotherapy drugs had not been fully evaluated for
Japanese pancreatic cancer patients. Therefore, we carried out a phase II study
to examine the efficacy and safety of FOLFIRINOX in chemotherapy-naive Japanese
patients with metastatic pancreatic cancer. FOLFIRINOX (i.v. infusion of 85
mg/m(2) oxaliplatin, 180 mg/m(2) irinotecan, and 200 mg/m(2) l-leucovorin,
followed by a bolus of 400 mg/m(2) fluorouracil and a 46-h continuous infusion of
2400 mg/m(2) fluorouracil) was given every 2 weeks. The primary endpoint was the
response rate. The 36 enrolled patients received a median of eight (range, 1-25)
treatment cycles. The response rate was 38.9% (95% confidence interval [CI], 23.1
56.5); median overall survival, 10.7 months (95% CI, 6.9-13.2); and median
progression-free survival, 5.6 months (95% CI, 3.0-7.8). Major grade 3 or 4
toxicities included neutropenia (77.8%), febrile neutropenia (22.2%),
thrombocytopenia (11.1%), anemia (11.1%), anorexia (11.1%), diarrhea (8.3%),
nausea (8.3%), elevated alanine aminotransferase levels (8.3%), and peripheral
sensory neuropathy (5.6%). Febrile neutropenia occurred only during the first
cycle. There were no treatment-related deaths. FOLFIRINOX can be a standard
regimen showing favorable efficacy and acceptable toxicity profile in
chemotherapy-naive Japanese patients with metastatic pancreatic cancer.
PMID- 25117730
TI - Defined serum- and xeno-free cryopreservation of mesenchymal stem cells.
AB - Mesenchymal stem cells (MSCs) have vast potential in cell therapy, and are
experimentally used in the clinic. Therefore, it is critical to find a serum- and
xeno-free cryopreservation method. The aim of this study was to compare two serum
and xeno-free cryoprotectants for MSCs. Adipose tissue MSCs (Ad-MSCs) and bone
marrow MSCs (BM-MSCs) were cryopreserved in two cryoprotectants: the defined
serum- and xeno-free STEM-CELLBANKERTM (CB) and 10 % dimethyl sulfoxide (DMSO) in
a xeno-free serum replacement cell culture medium and compared to non
cryopreserved MSCs. MSCs cryopreserved in CB or DMSO had similar morphology and
surface marker expression compared to their respective non-cryopreserved MSC. Ad
MSCs and BM-MSC in both cryoprotectant media exhibited reduced mean fluorescence
intensity (MFI) for CD105, BM-MSCs for CD73 and Ad-MSC increased MFI for HLA
class I compared to non-cryopreserved MSCs. Population doubling time of CB
cryopreserved and non-cryopreserved Ad-MSCs was similar (38.1 +/- 13.6 and 36.8
+/- 12.1 h), but somewhat higher when cryopreserved in DMSO (42.2 +/- 10.8 h). BM
MSCs had higher population doubling time (CB 47.7 +/- 11.4 and DMSO 62.3 +/- 32.9
h respectively, p < 0.05) compared to Ad-MSCs. The viability of Ad-MSCs was
significantly higher after cryopreservation in CB compared to DMSO (90.4 +/- 4.5
% vs. 79.9 +/- 3.8 % respectively). Ad-MSCs and BM-MSCs retained their mesodermal
differentiation potential when cryopreserved in both cryoprotectants. The
characteristics of Ad-MSCs post-thawing are better preserved by CB than by DMSO
in serum- and xeno-free medium. Furthermore, Ad-MSCs and BM-MSCs are differently
affected by the cryoprotectants, which may have implications for cell therapy.
PMID- 25117739
TI - Vanadium complexes with multidentate amine bisphenols.
AB - The reaction of VO(acac)2 (acac(-) = acetyl acetonate) with tripodal glycine
bisphenol H3L(1) under an ambient atmosphere yields a hexacoordinated
vanadium(iv) complex [V(acac)(L(1))] (1). The corresponding reactions with
tripodal 2-propanolamine bisphenol H3L(2) and potentially pentadentate
ethoxyethanolamine bisphenol H3L(3) lead to the oxidation of the metal centre and
formation of mononuclear oxovanadium(v) complexes [VO(L(2))] (2) and [VO(L(3))]
(3), respectively. Alternatively, these latter two complexes can be prepared
using VOSO4.5H2O or VO(OPr)3 as a precursor. The CV of 1 in an ACN solution shows
a reversible one-electron process at E1/2 = +1.18 V, whereas 2 and 3 have an
irreversible redox response at -1.6 V and -1.2 V, respectively. Complexes 2 and 3
show moderate activity in the epoxidation of cis-cyclooctene by tert-BuOOH at 50
degrees C.
PMID- 25117740
TI - Dialysis exercise team: the way to sustain exercise programs in hemodialysis
patients.
AB - Patients affected by end-stage renal disease (ESRD) show quite lower physical
activity and exercise capacity when compared to healthy individuals. In addition,
a sedentary lifestyle is favoured by lack of a specific counseling on exercise
implementation in the nephrology care setting. Increasing physical activity level
should represent a goal for every dialysis patient care management. Three crucial
elements of clinical care may contribute to sustain a hemodialysis exercise
program: a) involvement of exercise professionals, b) real commitment of
nephrologists and dialysis professionals, c) individual patient adaptation of the
exercise program. Dialysis staff have a crucial role to encourage and assist
patients during intra-dialysis exercise, but other professionals should be
included in the ideal "exercise team" for dialysis patients. Evaluation of
general condition, comorbidities (especially cardiovascular), nutritional status
and physical exercise capacity are mandatory to propose an exercise program, in
either extra-dialysis or intra-dialysis setting. To this aim, nephrologist should
lead a team of specialists and professionals including cardiologist,
physiotherapist, exercise physiologist, renal dietician and nurse. In this
scenario, dialysis nurses play a pivotal role since they guarantee a constant and
direct approach. Unfortunately dialysis staff may often lack of information and
formation about exercise management while they take care patients during the
dialysis session. Building an effective exercise team, promoting the culture of
exercise and increasing physical activity levels lead to a more complete and
modern clinical care management of ESRD patients.
PMID- 25117741
TI - Media reporting of neuroscience depends on timing, topic and newspaper type.
AB - The rapid developments in neuroscientific techniques raise high expectations
among the general public and therefore warrant close monitoring of the
translation to the media and daily-life applications. The need of empirical
research into neuroscience communication is emphasized by its susceptibility to
evoke misconceptions and polarized beliefs. As the mass media are the main
sources of information about (neuro-)science for a majority of the general
public, the objective of the current research is to quantify how critically and
accurately newspapers report on neuroscience as a function of the timing of
publication (within or outside of periods of heightened media attention to
neuroscience, termed "news waves"), the topic of the research (e.g. development,
health, law) and the newspaper type (quality, popular, free newspapers). The
results show that articles published during neuroscience news waves were less
neutral and more optimistic, but not different in accuracy. Furthermore, the
overall tone and accuracy of articles depended on the topic; for example,
articles on development often had an optimistic tone whereas articles on law were
often skeptical or balanced, and articles on health care had highest accuracy.
Average accuracy was rather low, but articles in quality newspapers were
relatively more accurate than in popular and free newspapers. Our results provide
specific recommendations for researchers and science communicators, to improve
the translation of neuroscience findings through the media: 1) Caution is
warranted during periods of heightened attention (news waves), as reporting tends
to be more optimistic; 2) Caution is also warranted not to follow topic-related
biases in optimism (e.g., development) or skepticism (e.g., law); 3) Researchers
should keep in mind that overall accuracy of reporting is low, and especially
articles in popular and free newspapers provide a minimal amount of details. This
indicates that researchers themselves may need to be more active in preventing
misconceptions to arise.
PMID- 25117742
TI - Pressure response of amide one-bond J-couplings in model peptides and proteins.
AB - The pressure dependence of the one-bond indirect spin-spin coupling constants
(1)J(N-H) was studied in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH2 (with
Xxx being one of the 20 proteinogenic amino acids). The response of the (1)J(N-H)
coupling constants is amino acid type specific, with an average increase of its
magnitude by 0.6 Hz at 200 MPa. The variance of the pressure response is rather
large, the largest pressure effect is observed for asparagine where the coupling
constant becomes more negative by -2.9 Hz at 200 MPa. The size of the J-coupling
constant at high pressure is positively correlated with its low pressure value
and the beta-propensity, and negatively correlated with the amide proton shift
and the first order nitrogen pressure coefficient and the electrostatic solvation
free energy.
PMID- 25117743
TI - Volumetric MR-guided high-intensity focused ultrasound versus uterine artery
embolisation for treatment of symptomatic uterine fibroids: comparison of symptom
improvement and reintervention rates.
AB - PURPOSE: To compare the effectiveness of magnetic resonance-guided high-intensity
focused ultrasound (MR-HIFU) with that of uterine artery embolisation (UAE) for
treatment of uterine fibroids. METHODS: Between January 2010 and January 2013, 51
women with symptomatic uterine fibroids underwent MR-HIFU. Follow-up and MR
imaging were compared to 68 women treated with UAE, who fulfilled eligibility
criteria for MR-HIFU - e.g., size (<= 12 cm) and number (<= 5) of fibroids. We
compared median symptom severity (tSSS), total health-realted quality of life
(HRQoL) scores, and reintervention rates. The adjusted effect on symptom relief
and HRQoL improvement was calculated using multivariable linear regression. Cox
regression was applied to calculate the adjusted risk of reintervention between
both treatments. RESULTS: Median tSSS improved significantly from baseline to
three-month follow-up (P < 0.001) for both MR-HIFU (53.1 (IQR [40.6-68.8]) to
34.4 (IQR [21.9-46.9]) and UAE (65.3 (IQR [56.3-74.2]) to 21.9 (IQR [9.4-34.4]).
In addition, significantly better HRQoL scores were observed after three months
(P < 0.001). However, in multivariate analysis, UAE had a stronger effect on
symptom relief and HRQoL improvement than MR-HIFU (P < 0.001). Patients treated
with MR-HIFU had a 7.1 (95 % CI [2.00-25.3]; P = 0.002) times higher risk of
reintervention within 12 months (18/51 vs. 3/68). CONCLUSION: Both MR-HIFU and
UAE result in significant symptom relief related to uterine fibroids. However, MR
HIFU is associated with a higher risk of reintervention. KEY POINTS: * This study
compared outcomes between volumetric MR-HIFU and UAE for uterine fibroids. * Both
MR-HIFU and UAE result in significant symptom relief and quality of life
improvement. * UAE had a stronger positive effect on the clinical outcomes. *
Reintervention rate after MR-HIFU ablation was significantly higher than after
UAE.
PMID- 25117744
TI - The clinical utility of reduced-distortion readout-segmented echo-planar imaging
in the head and neck region: initial experience.
AB - OBJECTIVES: To evaluate whether readout-segmented echo-planar imaging (RS-EPI)
diffusion weighted image (DWI) can diminish image distortion in the head and neck
area, compared with single-shot (SS)-EPI DWI. METHODS: We conducted phantom and
patient studies using 3 T magnetic resonance imaging (MRI) with a 16-channel
coil. For the phantom study, we evaluated distortion and signal homogeneity in
gel phantoms. For the patient study, 29 consecutive patients with clinically
suspicious parotid lesions were prospectively enrolled. RS-EPI and SS-EPI DWI
were evaluated by two independent readers for identification of organ/lesion and
distortion, using semiquantitative scales and quantitative scores. Apparent
diffusion coefficient (ADC) values and contrast-noise ratios of parotid tumours
(if present; n = 15) were also compared. RESULTS: The phantom experiments showed
that RS-EPI provided less distorted and more homogeneous ADC maps than SS-EPI. In
the patient study, RS-EPI was found to provide significantly less distortion in
almost all organs/lesions (p < 0.05), according to both semiquantitative scales
and quantitative scores. There was no significant difference in ADC values and
contrast-noise ratios between the two DWI techniques. CONCLUSIONS: The distortion
in DWI was significantly reduced with RS-EPI in both phantom and patient studies.
The RS-EPI technique provided more homogenous images than SS-EPI, and can
potentially offer higher image quality in the head and neck area. KEY POINTS: The
distortion in DWI is significantly reduced with RS-EPI compared with SS-EPI.
Structures in the head and neck were identified more clearly using RS-EPI. No
significant difference in ADC values was found between the techniques.
PMID- 25117745
TI - Impact of contrast-enhanced ultrasound in the study of hepatic artery
hypoperfusion shortly after liver transplantation: contribution to the diagnosis
of artery steal syndrome.
AB - OBJECTIVE: To assess the value of contrast-enhanced ultrasound (CEUS) in the
absence of hepatic artery signal on Doppler ultrasound (DUS) in the immediate
postoperative period after liver transplant. METHODS: This prospective study
included 675 consecutive liver transplants. Patients without hepatic artery
signal by DUS within 8 days post-transplant were studied with CEUS. If it
remained undetectable, a thrombosis was suspected. In patent hepatic artery, a
DUS was performed immediately after CEUS; if low resistance flow was detected, an
arteriography was indicated. Patients with high resistance waveform underwent
DUS+/CEUS follow-up. Arteriography was indicated when abnormal flow persisted for
more than 5 days or liver dysfunction appeared. RESULTS: Thirty-four patients
were studied with CEUS. In 11 patients CEUS correctly diagnosed hepatic artery
thrombosis. In two out of 23 non-occluded arteries, a low resistance flow lead to
a diagnosis of stenosis/proximal thrombosis. Twenty-one patients had absence of
diastolic flow, which normalized in the follow-up in 13 patients. In the
remaining eight patients, splenic artery steal syndrome (ASS) was diagnosed.
CONCLUSIONS: CEUS allows us to avoid invasive tests in the diagnostic work-up
shortly after liver transplant. It identifies the hepatic artery thrombosis and
points to a diagnosis of ASS. KEY POINTS: * CEUS is useful in the diagnostic work
up shortly after liver transplant * CEUS identifies the hepatic artery thrombosis
with reliability * There is little information about DUS and CEUS findings in the
ASS * DUS and CEUS offer functional information useful in the diagnosis of ASS.
PMID- 25117746
TI - Does tumoral (111)In-ibritumomab accumulation correlate with therapeutic effect
and outcome in relapsed or refractory low-grade B-cell lymphoma patients
undergoing (90)Y-ibritumomab radioimmunotherapy?
AB - OBJECTIVES: The aim of this study was to determine whether tumoral (111)In
ibritumomab accumulation on pre-treatment imaging correlates with therapeutic
responses and progression-free survival (PFS) in patients with non-Hodgkin's
lymphoma (NHL) undergoing (90)Y-ibritumomab radioimmunotherapy (RIT). METHODS:
This was a retrospective study of 39 patients with low-grade B-cell NHL treated
with RIT. We classified the patients into positive and negative groups according
to the presence or absence of tumoral (111)In-ibritumomab accumulation on pre
treatment (111)In-ibritumomab examinations. We then determined the correlation
between the (111)In-ibritumomab imaging findings and the patients' therapeutic
responses and PFS. RESULTS: Tumoral (111)In-ibritumomab accumulation was positive
in 64.1% and negative in 35.9% of the patients. The (111)In-positive patients had
a significantly higher overall response rate (ORR) compared to the (111)In
negative patients (100.0% vs. 78.6%, p = 0.02). The (111)In-negative patients
with advanced disease (stages III/IV) had a significantly lower ORR (40%) and a
significantly higher rate of progressive disease (40.0%) compared to those of the
(111)In-negative patients with limited disease (stages I/II) (100% and 0%, p =
0.009 each). However, these two groups had similar 2-year PFS rates (65.0% vs.
50.0%, p = 0.80). CONCLUSIONS: (111)In-ibritumomab imaging findings seem to
correlate with ORR and the progressive disease rate after RIT, but not with PFS.
KEY POINTS: All 39 NHL patients had tumoral accumulation on pretreatment FDG
PET/CT. 64.1% of NHL patients had tumoral accumulation on a pretreatment (111) In
ibritumomab examination. (90) Y-ibritumomab RIT resulted in high overall response
and complete remission rates. (111) In-ibritumomab avidity of lymphoma lesions
could predict a strong therapeutic effect. (111) In-ibritumomab imaging findings
did not correlate with progression-free survival.
PMID- 25117747
TI - Multiparametric magnetic resonance imaging for the differentiation of low and
high grade clear cell renal carcinoma.
AB - PURPOSE: To retrospectively evaluate the ability of magnetic resonance (MR)
imaging to differentiate low from high Fuhrman grade renal cell carcinoma (RCC).
MATERIALS AND METHODS: MR images from 80 consecutive pathologically proven RCC
(57 clear cell, 16 papillary and 7 chromophobe) were evaluated. Double-echo
chemical shift, dynamic contrast-enhanced T1- and T2-weighted images and apparent
diffusion coefficient (ADC) maps were reviewed independently. Signal intensity
index (SII), tumour-to-spleen SI ratio (TSR), ADC ratio, wash-in (WiI) and wash
out indices (WoI) between different phases were calculated and compared to
pathological grade and size. The Fuhrman scoring system was used. Low grade
(score <= 2) and high grade (score >= 3) tumours were compared using univariate
and multivariate analyses. RESULTS: No associations between grade and imaging
factors were found for papillary and chromophobe RCCs. For clear cell RCCs, there
was a significant association between the grade and parenchymal WiI (WiI2) (P =
0.02) or ADCr (P = 0.03). A significant association between tumour grade and size
(P = 0.01), WiI2 (P = 0.02) and ADCr (P = 0.05) remained in multivariate
analysis. CONCLUSIONS: Multiparametric MRI can be used to accurately
differentiate low Fuhrman grade clear cell RCC from high grade. High Fuhrman
grade (>= 3) RCCs were larger, had lower parenchymal wash-in indices and lower
ADC ratios than low grade. KEY POINTS: * Fuhrman grade of clear cell RCC can be
differentiated with multiparametric MR imaging. * Fuhrman grade significantly
differed for size, parenchymal wash-in index and ADC ratio. * No significant
associations were found for papillary and chromophobe renal cell carcinoma.
PMID- 25117748
TI - Interleukin-6 concentrations in the urine and dipstick analyses were related to
bacteriuria but not symptoms in the elderly: a cross sectional study of 421
nursing home residents.
AB - BACKGROUND: Up to half the residents of nursing homes for the elderly have
asymptomatic bacteriuria (ABU), which should not be treated with antibiotics. A
complementary test to discriminate between symptomatic urinary tract infections
(UTI) and ABU is needed, as diagnostic uncertainty is likely to generate
significant antibiotic overtreatment. Previous studies indicate that Interleukin
6 (IL-6) in the urine might be suitable as such a test. The aim of this study was
to investigate the association between laboratory findings of bacteriuria, IL-6
in the urine, dipstick urinalysis and newly onset symptoms among residents of
nursing homes. METHODS: In this cross sectional study, voided urine specimens for
culture, urine dipstick and IL-6 analyses were collected from all residents
capable of providing a voided urine sample, regardless of the presence of
symptoms. Urine specimens and symptom forms were provided from 421 residents of
22 nursing homes. The following new or increased nonspecific symptoms occurring
during the previous month were registered; fatigue, restlessness, confusion,
aggressiveness, loss of appetite, frequent falls and not being herself/himself,
as well as symptoms from the urinary tract; dysuria, urinary urgency and
frequency. RESULTS: Recent onset of nonspecific symptoms was common among elderly
residents of nursing homes (85/421). Urine cultures were positive in 32%
(135/421), Escherichia coli was by far the most common bacterial finding.
Residents without nonspecific symptoms had positive urine cultures as often as
those with nonspecific symptoms with a duration of up to one month. Residents
with positive urine cultures had higher concentrations of IL-6 in the urine (p <
0.001). However, among residents with positive urine cultures there were no
differences in IL-6 concentrations or dipstick findings between those with or
without nonspecific symptoms. CONCLUSIONS: Nonspecific symptoms among elderly
residents of nursing homes are unlikely to be caused by bacteria in the urine.
This study could not establish any clinical value of using dipstick urinalysis or
IL-6 in the urine to verify if bacteriuria was linked to nonspecific symptoms.
PMID- 25117749
TI - Vulnerabilities faced by the children of sex workers in two Mexico-US border
cities: a retrospective study on sexual violence, substance use and HIV risk.
AB - Most studies of female sex workers (FSWs) conducted in the Mexico-US border
region have focused on individual HIV risk, centered on sexual behaviors and
substance abuse patterns. Little attention has been drawn to the reality that sex
workers are often parents whose children potentially face vulnerabilities unique
to their family situation. The objective of the present study was to identify the
vulnerabilities faced by the children of FSWs in two Mexican-US border cities.
From 2008 to 2010, 628 FSW-injection drug users underwent interviewer
administered surveys and HIV/STI testing. Approximately one in five participants
(20%) reported having a parent involved in sex work and majority referred it was
their mother (88%). Close to one-third of participants (31%) reported first
injecting drugs <18 years of age, and 33% reported they began working regularly
as a prostitute <18 years of age. First drinking alcohol <18 years old (AOR =
1.87, 95%CI: 1.13-3.08), lifetime cocaine use (AOR = 1.76, 95%CI: 1.09-2.84),
ever being forced or coerced into non-consensual sex as a minor (<18 years of
age; AOR = 1.54, 95%CI: 1.01-2.35), and injecting drugs with used syringes in the
prior month (AOR = 1.63, 95%CI: 1.07-2.49) were the factors associated with
having had a parent involved in sex work. These findings begin to lay the
groundwork for understanding the potential vulnerabilities faced by the children
of sex workers. Understanding these potential needs is necessary for creating
relevant, evidence-based interventions focused on supporting these women.
PMID- 25117750
TI - Progression of cardio-metabolic risk factors in subjects born small and large for
gestational age.
AB - BACKGROUND: Subjects born small (SGA) and large (LGA) for gestational age have an
increased risk of cardio-metabolic alterations already during prepuberty.
Nevertheless, the progression of their cardio-metabolic profile from childhood to
adolescence has not been fully explored. Our aim was to assess potential changes
in the cardio-metabolic profile from childhood to adolescence in subjects born
SGA and LGA compared to those born appropriate (AGA) for gestational age.
METHODS: This longitudinal study included 35 AGA, 24 SGA and 31 LGA subjects
evaluated during childhood (mean age (+/- SD) 8.4 +/- 1.4 yr) and then re
assessed during adolescence (mean age 13.3 +/- 1.8 yr). BMI, blood pressure,
insulin resistance (fasting insulin, HOMA-IR) and lipids were assessed. A cardio
metabolic risk z-score was applied and this consisted in calculating the sum of
sex-specific z-scores for BMI, blood pressure, HOMA-IR, triglycerides and
triglycerides:high-density lipoprotein cholesterol ratio. RESULTS: Fasting
insulin and HOMA-IR were higher in SGA and LGA than AGA subjects both during
childhood (all P<0.01) and adolescence (all P<0.01). Similarly, the clustered
cardio-metabolic risk score was higher in SGA and LGA than AGA children (both
P<0.05), and these differences among groups increased during adolescence (both
P<0.05). Of note, a progression of the clustered cardio-metabolic risk score was
observed from childhood to adolescence within SGA and within LGA subjects (both
P<0.05). CONCLUSIONS: SGA and LGA subjects showed an adverse cardio-metabolic
profile during childhood when compared to AGA peers, with a worsening of this
profile during adolescence. These findings indicate an overtime progression of
insulin resistance and overall estimated cardiovascular risk from childhood to
adolescence in SGA and LGA populations.
PMID- 25117751
TI - Classification of CT pulmonary angiography reports by presence, chronicity, and
location of pulmonary embolism with natural language processing.
AB - In this paper we describe an efficient tool based on natural language processing
for classifying the detail state of pulmonary embolism (PE) recorded in CT
pulmonary angiography reports. The classification tasks include: PE present vs.
absent, acute PE vs. others, central PE vs. others, and subsegmental PE vs.
others. Statistical learning algorithms were trained with features extracted
using the NLP tool and gold standard labels obtained via chart review from two
radiologists. The areas under the receiver operating characteristic curves (AUC)
for the four tasks were 0.998, 0.945, 0.987, and 0.986, respectively. We compared
our classifiers with bag-of-words Naive Bayes classifiers, a standard text mining
technology, which gave AUC 0.942, 0.765, 0.766, and 0.712, respectively.
PMID- 25117752
TI - Seasonal variations of vitamin D concentrations in pregnant women and neonates in
Slovenia.
AB - OBJECTIVE: While foreign research shows a high prevalence of vitamin D deficiency
in pregnant women and consequently in neonates, we do not have any data on
vitamin D concentration in these risk groups for Slovenia. We performed a
prospective study to evaluate vitamin D concentration in pregnant women and
neonates in Maribor region. STUDY DESIGN: We determined 25-hydroxy-vitamin D
concentration from blood samples taken before delivery from 100 pregnant women
who gave birth in Maribor University Clinical Centre in September and December
2013, respectively, and from the cord blood of their neonates. We collected data
on nutrition and sun exposure during pregnancy. We calculated the vitamin D
concentrations in pregnant women and neonates according to season of birth and
use of nutrition supplements, determined the vitamin D levels in some pregnancy
complications and checked the correlation of maternal and neonatal vitamin D
concentrations. RESULTS: The average vitamin D concentration in the September
group was 54.3+/-25.2nmol/L, and in the December group 33.3+/-18.6nmol/L
(p<0.001). Optimal vitamin D concentration (>80nmol/L) was reached by 12.0% of
pregnant women in September and by only 2.0% in December. Women who took
nutrition supplements containing vitamin D during pregnancy had significantly
higher vitamin D levels than those who did not (September 68.9+/-27.0nmol/L vs.
46.5+/-20.3nmol/L, p<0.001; December 38.7+/-17.9nmol/L vs. 30.2+/-18.4nmol/L,
p=0.028). Neonates had higher average levels of vitamin D than their mothers but
there was a good correlation between maternal and neonatal vitamin D values.
CONCLUSION: Vitamin D deficiency is very common in pregnant women in Slovenia as
well, especially in winter and in those women who do not take nutrition
supplements containing vitamin D.
PMID- 25117753
TI - Fall in genital warts diagnoses in the general and indigenous Australian
population following implementation of a national human papillomavirus
vaccination program: analysis of routinely collected national hospital data.
AB - BACKGROUND: Human papillomavirus (HPV) vaccination targeting females aged 12-13
years commenced in Australia in 2007, with catch-up vaccination of females aged
13-26 years continuing to 2009. Whole-population analyses, including effects on
the Indigenous population, have not previously been reported. METHODS: All
hospital admissions between 1999-2011 involving a diagnosis of genital warts were
obtained from a comprehensive national database. We compared the age-specific
rates before to those after implementation of the vaccination program, according
to sex and other characteristics. RESULTS: Admission rates decreased from mid
2007 in females aged 12-17 years (annual decline, 44.1% [95% confidence interval
{CI}, 35.4%-51.6%]) and from mid-2008 in females and males aged 18-26 years
(annual declines, 31.8% [95% CI, 28.4%-35.2%] and 14.0% [95% CI, 5.1%-22.1%],
respectively). The overall reductions from 2006-2007 to 2010-2011 were 89.9% (95%
CI, 84.4%-93.4%) for females aged 12-17 years, 72.7% (95% CI, 67.0%-77.5%) for
females aged 18-26 years, and 38.3% (95% CI, 27.7%-47.2%) for males aged 18-26
years. Compared with the average annual number before program implementation,
about 1000 fewer hospital admissions involved a warts diagnosis during 2010-2011.
Reductions after program implementation were similar for Indigenous (86.7% [95%
CI, 76.0-92.7]) and non-Indigenous (76.1% [95% CI, 71.6%-79.9%]) females aged 15
24 years (P(heterogeneity) = .08). CONCLUSIONS: National population-based
hospital data confirm previous clinic-based reports of a marked decline in
genital warts diagnoses among young people in Australia after program
implementation, including indirect benefits to males. The impact of HPV
vaccination appears to be similar in young Indigenous and non-Indigenous females.
PMID- 25117754
TI - Measles outbreak response among adolescent and adult Somali refugees displaced by
famine in Kenya and Ethiopia, 2011.
AB - BACKGROUND: The refugee complexes of Dadaab, Kenya, and Dollo-Ado, Ethiopia,
experienced measles outbreaks during June-November 2011, following a large influx
of refugees from Somalia. METHODS: Line-lists from health facilities were used to
describe the outbreak in terms of age, sex, vaccination status, arrival date,
attack rates (ARs), and case fatality ratios (CFRs) for each camp. Vaccination
data and coverage surveys were reviewed. RESULTS: In Dadaab, 1370 measles cases
and 32 deaths (CFR, 2.3%) were reported. A total of 821 cases (60.1%) were aged
>=15 years, 906 (82.1%) arrived to the camps in 2011, and 1027 (79.6%) were
unvaccinated. Camp-specific ARs ranged from 212 to 506 cases per 100 000 people.
In Dollo-Ado, 407 cases and 23 deaths (CFR, 5.7%) were reported. Adults aged >=15
years represented 178 cases (43.7%) and 6 deaths (26.0%). Camp-specific ARs
ranged from 21 to 1100 cases per 100 000 people. Immunization activities that
were part of the outbreak responses initially targeted children aged 6 months to
14 years and were later expanded to include individuals up to 30 years of age.
CONCLUSIONS: The target age group for outbreak response-associated immunization
activities at the start of the outbreaks was inconsistent with the numbers of
cases among unvaccinated adolescents and adults in the new population. In
displacement of populations from areas affected by measles outbreaks, health
authorities should consider vaccinating adults in routine and outbreak response
activities.
PMID- 25117755
TI - In vivo prediction of tuberculosis-associated cavity formation in rabbits.
AB - The presence of cavitary lesions in patients with tuberculosis poses a
significant clinical concern due to the risk of infectivity and the risk of
antibiotic treatment failure. We describe 2 algorithms that use noninvasive
positron emission tomography (PET) and computed tomography (CT) to predict the
development of cavitary lesions in rabbits. Analysis of the PET region of
interest predicted cavitary disease with 100% sensitivity and 76% specificity,
and analysis of the CT region of interest predicted cavitary disease with 83.3%
sensitivity and 76.9% specificity. Our results show that restricting our analysis
to regions with high [(18)F]-fluorodeoxyglucose uptake provided the best
combination of sensitivity and specificity.
PMID- 25117756
TI - Disease-specific T-helper cell polarizing function of lesional dendritic cells in
different types of chronic rhinosinusitis with nasal polyps.
AB - RATIONALE: Although eosinophilic and noneosinophilic chronic rhinosinusitis with
nasal polyps (CRSwNP) exhibit distinct T-helper (Th) responses, the underlying
mechanisms remain unclear. OBJECTIVES: To clarify the phenotypes and Th-cell
polarizing functions of dendritic cells (DCs) in different types of CRSwNP.
METHODS: DC subsets, their surface phenotypes, and Th-cell subsets were studied
by means of immunohistochemistry and flow cytometry. The sorted lesional DCs were
activated or cultured with autologous naive CD4(+) T cells, and cytokine
production was determined by ELISA. Thymic stromal lymphopoietin and osteopontin
expression were detected by means of reverse-transcriptase polymerase chain
reaction. MEASUREMENTS AND MAIN RESULTS: Although elevated local Th1 and Th17
cells were noted in both eosinophilic and noneosinophilic CRSwNP, increased Th2
cells were found only in eosinophilic CRSwNP. Increased numbers of myeloid DCs,
plasmacytoid DCs, and their activated subsets were found in both types of CRSwNP,
but only myeloid DCs and plasmacytoid DCs from eosinophilic CRSwNP demonstrated
an up-regulation of OX40 ligand (OX40L) and programmed death ligand 1(PD-L1)
expression. Lesional DCs from both types of CRSwNP produced enhanced levels of IL
12, IL-6, and transforming growth factor-beta, and induced increased Th1 and Th17
responses; in contrast, only DCs from eosinophilic CRSwNP induced obviously
enhanced Th2 responses, when cocultured with naive CD4(+) T cells. Blockade of
OX40L and PD-L1 on lesional DCs from eosinophilic CRSwNP suppressed Th2
responses, but promoted Th1 responses in DC-T cell coculture. CONCLUSIONS:
Distinct subsets of lesional DCs were found in eosinophilic and noneosinophilic
CRSwNP, where OX40L/PD-L1(+) lesional DCs in eosinophilic CRSwNP could prime Th2
cells, whereas the low OX40L/PD-L1-expressing lesional DCs in noneosinophilic
CRSwNP primarily induced Th1/Th17 cells.
PMID- 25117758
TI - Chronic kidney disease (CKD) as a systemic disease: whole body autoregulation and
inter-organ cross-talk.
AB - The inter-organ cross-talk and the functional integration of organ systems is an
exceedingly complex process which until now has been investigated with a
reductionist approach. CKD perturbs the inter-organ cross-talk and demands
central resetting of autonomic (nervous) control of organ systems. Due to
limitations inherent to the reductionist approach, we currently identify CKD
related pseudo-syndromes and largely fail at describing the complex systemic
inter-relationships set into motion by renal damage and renal dysfunction. A
mature technology for a system-analysis approach to physiology and
pathophysiology of CKD now exists. System biology will allow in depth
understanding of complex diseases like CKD and will set the stage for predictive,
preventive and personalized medicine, a long-standing dream of doctors and
patients alike.
PMID- 25117757
TI - PD-1 expression on peripheral blood T-cell subsets correlates with prognosis in
non-small cell lung cancer.
AB - PD-1 expression in peripheral blood T-cells has been reported in several kinds of
cancers, including lung cancer. However, the relationship between PD-1 expression
in peripheral blood T-cells and prognosis after treatment with a cancer vaccine
has not been reported. To elucidate this relationship, we analyzed PD-1
expression in the peripheral blood T-cells of patients with non-small cell lung
cancer. The blood samples used in this study were obtained from patients enrolled
in phase II clinical trials of a personalized peptide vaccine. Seventy-eight
samples obtained before and after a single vaccination cycle (consisting of six
or eight doses) were subjected to the analysis. PD-1 was expressed on lymphocytes
in the majority of samples. The relative contents of PD1(+) CD4(+) T-cells
against total lymphocytes before and after the vaccination cycle correlated with
overall survival (OS) with a high degree of statistical significance (P < 0.0001
and P = 0.0014). A decrease in PD-1(+) CD8(+) T-cells after one cycle of
vaccination also correlated with longer OS (P = 0.032). The IgG response to the
non-vaccinated peptides suggested that the epitope spreading seemed to occur more
frequently in high-PD-1(+) CD4(+) T-cell groups. Enrichment of CD45RA(-) CCR7(-)
effector-memory phenotype cells in PD-1(+) T-cells in PBMCs was also shown. These
results suggest that PD-1 expression on the peripheral blood T-cell subsets can
become a new prognostic marker in non-small cell lung cancer patients treated
with personalized peptide vaccination.
PMID- 25117759
TI - Physical and mental decline and yet rather happy? A study of Danes aged 45 and
older.
AB - OBJECTIVES: Little is known about whether the feeling of happiness follows the
age-related decline in physical and mental functioning. The objective of this
study was to analyze differences with age in physical and mental functions and in
the feeling of happiness among Danes aged 45 years and older. METHOD: Three
Danish population-based surveys including 11,307 participants aged 45+ years, of
whom 2411 were in the age group of 90+, were conducted in the period 1995-2001.
The participation rate in the three surveys was between 63% and 82% and the same
design and the same instrument were used. Self-reported mobility, a cognitive
composite score, and a depression symptomatology score including a question about
happiness were assessed. T-score metric was used to compare across domains and
age groups. RESULTS: Overall, successively older age groups performed worse than
the youngest age group (45-49 years), and the estimated linear decline was
greater after age 70 than before age 70. For example, when comparing the oldest
age group (90+ years) with the youngest, the T-score differences were found to be
the largest for the mobility score (men: 40.2, women: 41.4), followed by the
cognitive function (men: 22.0, women: 24.9), and the total depression
symptomatology score (men: 15.5, women: 17.4). Conversely, the T-score difference
in happiness was small (men: 5.6, women: 6.0). CONCLUSION: Despite markedly
poorer physical and mental functions with increasing age, in this Danish sample
age did not seem to affect happiness to a similarly notable extent, although, in
this study, cohort and age effects cannot be disentangled.
PMID- 25117762
TI - Dinuclear Cu(II) complexes based on two flexible Schiff-base ligands and one
unusual in situ formed diphenolate 2,6-piperidin-4-one derivative.
AB - A dinuclear Cu(ii) complex [Cu2(L3)2].2H2O, having an unprecedented in situ
formed diphenolate 2,6-piperidin-4-one derived ligand produced from the flexible
Schiff-base ligand HL1, can be yielded as a side product in the presence of
Cu(OAc)2.H2O-NH3.H2O dissolved in methanol and acetone in addition to the
expected dinuclear Cu(ii) complex [Cu2(L1)4].
PMID- 25117760
TI - Estimating the number of hand, foot and mouth disease amongst children aged under
five in Beijing during 2012, based on a telephone survey of healthcare seeking
behavior.
AB - BACKGROUND: Over the last decade, increases in the number of outbreaks of hand,
foot and mouth disease (HFMD) have shifted the disease into the public health
spotlight in China. Children under the age of five years are particularly
susceptible, with fatalities recorded. However, estimating the burden of HFMD has
been difficult to conduct to date. METHODS: In 2012, a cross-sectional survey of
healthcare-seeking behaviour for HFMD was undertaken, using computer assisted
telephone interviewing (CATI) technology. Sample of telephone numbers was
obtained from the Beijing Immunization Information System. Respondents were
parents or guardians of children under the age of five. Multiplier model was used
to estimate the number of HFMD case, following the telephone survey of healthcare
seeking behavior. The number of laboratory-confirmed cases was also estimated
based on the monthly positive rate of each subtype of virus causing HFMD. The age
specific case fatality rate (CFR) was calculated based on the ratio of reported
deaths to the estimated number of cases. RESULTS: For children under five, the
consultation rate of parent-defined cases was estimated at 77.8% ((95% CI =
[75.2, 80.4]). Parents or legal guardians of children aged between two and four
years were more likely to seek healthcare than those of children aged less than
two years. For children under the age of five, we estimated that there were
40,165 (95% CI = [38,471, 41,974]) HFMD cases, with an incidence rate of 5.6%,
and 22,166 (95% CI = [21,150, 23,295]) laboratory-confirmed cases in Beijing
during 2012. The overall CFR was estimated at 10 deaths per 100,000 cases, while
for children aged less than two years it was 15.6 deaths per 100,000 cases.
CONCLUSIONS: Given the public health impact of HFMD in China, control measures
need to be prioritized for children < 2 years, due to the higher CFR in this age
group. Sentinel surveillance approaches could be used to monitor trends and the
impact of control measures.
PMID- 25117761
TI - Comparison of long-term clinical outcomes between sirolimus- and paclitaxel
eluting stents in real-world clinical practice.
AB - Advances in percutaneous coronary intervention (PCI) have improved the outcomes
of patients with coronary artery diseases. The advent of drug-eluting stents
(DES) has dramatically reduced the rate of revascularization. The first
generation DES has yielded the main role of PCI to the second-generation DES;
however, many patients had been implanted with the first-generation DES,
sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). Therefore, it
is of importance to detect the long-term clinical outcomes in patients who
underwent PCI with SES or PES. We analyzed data from our PCI cohort who underwent
PCI with first-generation DES at Juntendo University Hospital between August 2004
and June 2010. The index procedure was analyzed when patients underwent multiple
PCIs. Patients who were implanted with both SES and PES were excluded from this
study. The study ended on December 31, 2011. The primary outcome was a composite
of all-cause mortality and acute coronary syndrome (ACS). The secondary outcome
was the rate of target lesion revascularization (TLR) and stent thrombosis. We
analyzed data from 861 consecutive patients who underwent implantation of SES or
PES. The median follow-up period was 1671 days (interquartile range 1081 and
2105). Kaplan-Meier curves for the primary endpoint did not significantly differ
between the two groups (p = 0.8). The incidence of stent thrombosis was 1.4 and
1.8 per 1,000 person-years in the SES and PES groups, respectively (p = 0.9). The
rate of TLR was significantly lower in the SES, than the PES group (12.6 and 38.3
per 1,000 person-years, p = 0.03). The rate of TLR was lower in the group treated
with SES than PES, but the primary outcome comprising all-cause mortality and ACS
was comparable between the two groups.
PMID- 25117763
TI - Structure and mechanism of the unique C2 domain of Aida.
AB - Axin interactor, dorsalization-associated (Aida) was identified as a regulatory
factor that utilizes its C-terminal region to interact with axis formation
inhibitor (Axin). Aida abrogates the Axin-mediated Jun N-terminal kinase
activation required for proper dorsalization during zebrafish embryonic
development, and thus functions as a proventralization factor. Here, we report
the structure of Aida C-terminal fragments, which adopt a conventional C2 domain
topology. We also demonstrate that Aida can specifically bind to
phosphoinositides in a Ca(2+) -independent manner, and is able to associate with
the cell membrane via a novel positively charged surface, namely a basic loop.
Mutation of the positively charged patch on the basic loop leads to
destabilization of the Aida-membrane association or disruption of the Aida-Axin
interaction, resulting in impaired Jun N-terminal kinase inhibition. Together,
our findings provide a molecular basis for C2 domain-mediated Aida-membrane and
Aida-Axin associations. DATABASE: The atomic coordinates and structure factors of
the mouse Aida C2 domain (code: 2QZ5) and the zebrafish Aida C2 domain (code:
2QZQ) have been deposited in the Protein Data Bank (http://www.rcsb.org/)
STRUCTURED DIGITAL ABSTRACT: AIDA physically interacts with Axin by anti tag
coimmunoprecipitation (View interaction).
PMID- 25117764
TI - Predictors of health-related quality of life over time among adolescents and
young adults with sickle cell disease.
AB - Little is known about what factors affect the health-related quality of life
(HRQoL) of adolescents and young adults (AYAs) with sickle cell disease (SCD),
and how their HRQoL changes over time. This retrospective study included 87 AYAs
attending a SCD Adolescent Clinic who completed a measure of HRQoL at each visit
over the course of approximately 1.3 years. Results suggested that the following
were associated with poorer physical HRQoL: being female, more healthcare
utilization events, and presence of internalizing symptoms. Internalizing and
externalizing symptoms were the only factors correlated with poorer psychosocial
HRQoL. Generalized linear mixed models indicated that physical and psychosocial
HRQoL improved among all participants during the assessment period, and those
with externalizing behaviors reported faster improvement in physical HRQoL over
time. AYAs with SCD may benefit from early mental health screening and
intervention to optimize clinical care.
PMID- 25117766
TI - Enhancement mechanisms behind exclusive removal and selective recovery of copper
from salt solutions with an aminothiazole-functionalized adsorbent.
AB - The aminothiazole-functionalized adsorbent (CEAD) could exclusively remove and to
selectively recover copper. The adsorption and separation properties of Cu(II)
onto CEAD from aqueous media, with or without salts such as NaNO3, Ca(NO3)2 and
Ni(NO3)2, were systematically compared by carrying out single, binary and
multiple component static and dynamic experiments. In binary systems, the
adsorption capacities of Cu(II) were obviously increased by 39.47%, 47.37% and
57.89% with Ni(NO3)2, NaNO3 and Ca(NO3)2, respectively. Besides, simulation study
was performed to selectively recover Cu(II) from multi-component aqueous media,
with the separation factor of only 54.91 in aqueous media without salts. The
separation factor became infinite in the presence of NaNO3 and the enhancement
ratio for Cu(II) was raised by 126.31%. Dynamic adsorption could separate Cu(II)
and Ni(II) completely and the amount of effluent for pure Ni(II) increased to 127
BV with the help of NaNO3. In the predominant chelating mode simulated by density
functional theory calculation, a metal ion coordinated with three nitrogen atoms
and formed a chelating complex with two five-membered rings, and Cu(II) showed
stronger coordinating ability than Ni(II) did. Meanwhile, anions exerted
significant beneficial effects by electrostatic screening, and thus strengthened
the exclusive removal and selective recovery of Cu(II).
PMID- 25117765
TI - The different association of epicardial fat with coronary plaque in patients with
acute coronary syndrome and patients with stable angina pectoris: analysis using
integrated backscatter intravascular ultrasound.
AB - OBJECTIVES: We assessed the hypothesis that the epicardial fat is associated with
coronary lipid plaque. BACKGROUND: Epicardial fat volume (EFV) is increased in
patients with acute coronary syndrome (ACS), and lipid-rich plaques have been
associated with acute coronary events. METHODS: We enrolled 112 individuals who
underwent percutaneous coronary intervention (PCI) (66 with ACS; 46 with stable
angina pectoris [SAP]) and classified plaque components using integrated
backscatter intravascular ultrasound as calcified, fibrous, or lipid. Possible
effects of PCI on plaque data were minimized by assessing 10-mm vessel lengths
proximal to the culprit lesions. Total plaque volume and percentage volumes of
individual plaque components were calculated. EFV and abdominal visceral fat area
were measured using 64-slice computed tomography. RESULTS: ACS patients had
significantly higher EFV than did SAP patients (118 +/- 44 vs.101 +/- 41 mL, p =
0.019). In ACS patients, EFV was correlated with total plaque volume and
percentage of lipid plaque (r = 0.27 and 0.31, respectively; p < 0.05). Moreover,
an independent interaction between EFV and lipid-rich plaque (odds ratio, 1.04;
95% confidence interval, 1.00-1.07) were revealed. In contrast, in SAP patients,
EFV was positively correlated with body mass index and abdominal visceral fat
area but not with plaque characteristics. CONCLUSIONS: EFV was associated with
lipid-rich plaque in patients with ACS, whereas no correlation between EFV and
coronary plaque profile was apparent in SAP patients. Epicardial fat may have a
role in the development of lipid plaque, which contributes to the pathogenesis of
ACS.
PMID- 25117772
TI - Longer examination time improves detection of gastric cancer during diagnostic
upper gastrointestinal endoscopy.
AB - BACKGROUND & AIMS: It is not clear how the duration of upper endoscopy affects
the detection of cancer or premalignant lesions that increase the risk for
gastric cancer. We investigated whether the length of time spent performing
esophagogastroduodenoscopy (EGD) affects the detection of important pathologic
features of the stomach. METHODS: We collected data from 837 symptomatic
patients, during a 3-month period in 2010, who underwent a first diagnostic EGD
at a tertiary university hospital in Singapore. Endoscopists were classified as
fast or slow based on the mean amount of time it took them to perform a normal
EGD examination. We used logistic regression to compare between groups the
numbers of intestinal metaplasias, gastric atrophies, dysplasias, and cancers
detected, using histologic analysis of biopsy samples collected during endoscopy
as the standard. RESULTS: Of 224 normal endoscopies, the mean duration was 6.6
minutes (range, 2-32 min). When we used 7 minutes as the cut-off time, 8
endoscopists were considered to have short mean examination times (mean duration,
5.5 +/- 2.1 min; referred to as fast endoscopists), and 8 endoscopists were
considered to have long mean examination times (mean duration, 8.6 +/- 4.2 min;
referred to as slow endoscopists). Eleven cancers and 81 lesions considered to
pose risks for cancer were detected in 86 patients; 1.3% were determined to be
cancer, 1.0% were determined to be dysplasia, and 8.7% were determined to be
intestinal metaplasia and/or gastric atrophy. Slow endoscopists were twice as
likely to detect high-risk lesions as fast endoscopists (odds ratio, 2.50; 95%
confidence interval, 1.52-4.12), regardless of whether they were endoscopy staff
or trainees. The slow endoscopists also detected 3-fold more neoplastic lesions
(cancer or dysplasia; odds ratio, 3.42; 95% confidence interval, 1.25-10.38).
CONCLUSIONS: Endoscopists with mean EGD examination times longer than 7 minutes
identified a greater number of high-risk gastric lesions than faster
endoscopists. Examination time may be a useful indicator of quality assessment
for upper endoscopy. Studies are required to test these findings in different
populations.
PMID- 25117773
TI - Suboptimal surveillance for and knowledge of hepatocellular carcinoma among
primary care providers.
AB - BACKGROUND & AIMS: A large proportion of patients with cirrhosis are seen only by
their primary care provider (PCP). Surveillance for hepatocellular carcinoma
(HCC) therefore depends on PCPs in these cases. We aimed to assess PCP knowledge
and practice of HCC surveillance. METHODS: We contacted a random sample of 1000
North Carolina PCPs by mail. All PCPs contacted received an introductory letter
followed by a 12-item questionnaire addressing HCC surveillance knowledge and
practice. RESULTS: A total of 391 PCPs (39%) completed the survey; 89% saw
patients with cirrhosis in their practice, but only 45% screened for HCC. Among
PCPs who screened for HCC, the most common methods were ultrasound analysis and
measurement of alpha-fetoprotein level (66%). Reasons for surveillance included
supported by evidence (72%), recommended by medical societies (42%), and
malpractice liability for not performing surveillance (26%). Of PCPs who did not
screen, 84% referred to gastroenterologists for surveillance decisions, 24% were
unaware of recommendations, 8% were uncertain of the benefits, and 8% were
concerned about cost. Hepatic resection and liver transplantation were identified
as effective therapies by 67% and 56% of PCPs, respectively, but all other
effective therapies were identified by less than half (transarterial
chemoembolization by 42%, radiofrequency ablation by 35%, and sorafenib by 26%).
The ability to identify at least 1 effective therapy was associated independently
with surveillance (odds ratio, 2.1; 95% confidence interval, 1.1-4.0).
CONCLUSIONS: Most PCPs see patients with cirrhosis, but only a minority screen
for HCC. PCP knowledge of effective HCC therapy options is suboptimal. Efforts to
enlist PCPs in HCC surveillance may be best served by increasing their knowledge
of effective therapies.
PMID- 25117774
TI - Trials and tribulations in drug development for nonalcoholic steatohepatitis.
PMID- 25117776
TI - Prevalence of chronic narcotic use among children with inflammatory bowel
disease.
AB - BACKGROUND & AIMS: Narcotic analgesics are not recommended for long-term
management of pain for patients with inflammatory bowel disease (IBD),
particularly pediatric patients. We compared chronic use of narcotics among
children with IBD and the general population and investigated factors associated
with narcotic use in the pediatric IBD population. METHODS: This cross-sectional
study included children (younger than 18 years old) with continuous enrollment in
a large administrative claims database from 2010 through 2011 (n = 4,911,286).
Children with IBD were identified through diagnosis codes and dispensation of IBD
medication (n = 4344); they were matched for age, sex, and region with 5 children
without IBD (n = 21,720). Chronic narcotic use was defined as >=3 dispensements
of narcotics. We estimated prevalence odds ratios (PORs) and 95% confidence
intervals (CIs), comparing narcotic use on the basis of IBD status and evaluating
variables associated with narcotic use by patients with IBD by using conditional
and unconditional logistic regression. RESULTS: The prevalence of chronic
narcotic use was 5.6% among children with IBD vs 2.3% in the general population
(POR, 2.6; 95% CI, 2.2-3.0). Compared with the general population, POR for
chronic narcotic use was significantly higher for pediatric IBD patients with
psychological impairment (POR, 6.8; 95% CI, 4.3-10.6) than those without (POR,
2.3; 95% CI, 1.9-2.7). Older age, increased healthcare utilization, fracture, and
psychological impairment were strongly associated with chronic use of narcotics
among children with IBD. CONCLUSIONS: Chronic narcotic use is common in pediatric
IBD patients, particularly among those with anxiety and depression. Increased
awareness of psychological comorbidity, screening, and treatment may reduce
symptoms that lead to narcotic use and its complications.
PMID- 25117775
TI - The benefit-to-risk balance of combining infliximab with azathioprine varies with
age: a markov model.
AB - BACKGROUND & AIMS: Combination therapy with infliximab and azathioprine has
demonstrated benefit over monotherapy for moderate-to-severe Crohn's disease.
Clinical trials and models have not accounted for age-specific risks associated
with these therapies, including the risk of immunosuppression-related cancer and
infection. After accounting for these risks, the strategy yielding the greatest
benefit may vary with age. METHODS: We assessed age-specific risks and benefits
of combination therapy compared with infliximab monotherapy by using Markov
modeling. The base case was a 35-year-old male patient with a 1-year time
horizon. We assumed the incidence of lymphoma to be 5.28-fold higher with
combination therapy. Secondary analyses accounted for life expectancy, therapy
beyond 1 year, and age-specific surgical and infection risks. Quality-adjusted
life years (QALYs) were calculated for 25- to 75-year old individuals. RESULTS:
Combination therapy was found to be of greater benefit in the base case (0.7522
QALYs for combination therapy vs 0.7426 QALYs for monotherapy). Accounting for
life years lost, monotherapy was the best approach if the hazard ratio for
lymphoma with combination therapy was >8.1 patients who were 75 years old.
Monotherapy provided greater net benefit to patients 55, 65, or 75 years old if
therapy was extended for 9, 7, or 5 years, respectively. For 25-year-old men,
monotherapy resulted in fewer deaths but only yielded greater QALYs if the annual
incidence of hepatosplenic T-cell lymphoma exceeded 36/100,000 persons.
CONCLUSIONS: After accounting for age-specific risks of lymphoma, infection, and
surgical complications, benefits of combination therapy outweighed the risks as a
short-term and intermediate-term strategy for most patients with moderate-to
severe Crohn's disease who were younger than 65 years. For young male patients,
combination therapy yields greater QALYs but at cost of an increased risk of
death from lymphoma.
PMID- 25117777
TI - A panel to predict long-term outcome of infliximab therapy for patients with
ulcerative colitis.
AB - BACKGROUND & AIMS: Infliximab is effective for patients with refractory
ulcerative colitis (UC), but few factors have been identified that predict long
term outcome of therapy. We aimed to identify a panel of markers associated with
outcome of infliximab therapy to help physicians make personalized treatment
decisions. METHODS: We collected data from the first 285 patients with refractory
UC (41% female; median age, 39 y) treated with infliximab before July 2012 at
University Hospitals Leuven, in Belgium. We performed a Cox regression analysis
to identify independent factors that predicted relapse-free and colectomy-free
survival, and used these factors to create a panel of markers (risk panel).
RESULTS: During a median follow-up period of 5 years, 61% of patients relapsed
and 20% required colectomy. Independent predictors of relapse-free survival
included short-term complete clinical response (odds ratio [OR], 3.75; 95%
confidence interval [CI], 2.35-5.97; P < .001), mucosal healing (OR, 1.87; 95%
CI, 1.17-2.98; P = .009), and absence of atypical perinuclear antineutrophil
cytoplasmic antibodies (pANCA) (OR, 1.96; 95% CI, 1.23-3.12; P = .005).
Independent predictors of colectomy-free survival included short-term clinical
response (OR, 7.74; 95% CI, 2.76-21.68; P < .001), mucosal healing (OR, 4.02; 95%
CI, 1.16-13.97; P = .028), baseline level of C-reactive protein (CRP) of 5 mg/L
or less (OR, 2.95; 95% CI, 1.26-6.89; P = .012), and baseline level of albumin of
35 g/L or greater (OR, 3.03; 95% CI, 1.12-8.22; P = .029). Based on serologic
analysis of a subgroup of 112 patients, levels of infliximab greater than 2.5
MUg/mL at week 14 of treatment predicted relapse-free survival (P < .001) and
colectomy-free survival (P = .034). A risk panel that included levels of pANCA,
CRP, albumin, clinical response, and mucosal healing identified patients at risk
for UC relapse or colectomy (both P < .001). CONCLUSIONS: Clinical response and
mucosal healing were confirmed as independent predictors of long-term outcome
from infliximab therapy in patients with UC. We identified additional factors
(levels of pANCA, CRP, and albumin) to create a risk panel that predicts long
term outcomes of therapy. Serum levels of infliximab at week 14 of treatment also
were associated with patient outcomes. Our risk panel and short-term serum levels
of infliximab therefore might be used to guide therapy.
PMID- 25117778
TI - Intra-abdominal pressure measurements in term pregnancy and postpartum: an
observational study.
AB - OBJECTIVE: To determine intra-abdominal pressure (IAP) and to evaluate the
reproducibility of IAP-measurements using the Foley Manometer Low Volume (FMLV)
in term uncomplicated pregnancies before and after caesarean section (CS),
relative to two different reference points and to non-pregnant values. DESIGN:
Observational cohort study. SETTING: Secondary level referral center for feto
maternal medicine. POPULATION: Term uncomplicated pregnant women as the case
group and non-pregnant patients undergoing a laparoscopic assisted vaginal
hysterectomy (LAVH) as control group. METHODS: IAP was measured in 23 term
pregnant patients, before and after CS and in 27 women immediately after and 1
day after LAVH. The midaxillary line was used as zero-reference (IAPMAL) in all
patients and in 13 CS and 13 LAVH patients, the symphysis pubis (IAPSP) was
evaluated as additional zero-reference. Intraobserver correlation (ICC) was
calculated for each zero-reference. Paired student's t-tests were performed to
compare IAP values and Pearson's correlation was used to assess correlations
between IAP and gestational variables. MAIN OUTCOME MEASURES: ICC before and
after surgery, IAP before and after CS, IAP after CS and LAVH. RESULTS: The ICC
for IAPMAL before CS was lower than after (0.71 versus 0.87). Both mean IAPMAL
and IAPSP were significantly higher before CS than after: 14.0+/-2.6 mmHg versus
9.8+/-3.0 mmHg (p<0.0001) and 8.2+/-2.5 mmHg versus 3.5+/-1.9 mmHg (p = 0.010),
respectively. After CS, IAP was not different from values measured in the LAVH
group. CONCLUSION: IAP-measurements using FMLV is reproducible in pregnant women.
Before CS, IAP is increased in the range of intra-abdominal hypertension for non
pregnant individuals. IAP significantly decreases to normal values after
delivery.
PMID- 25117781
TI - Klein and Lacan meet 21st century schizoid man: fairy stories for the modern era.
AB - Melanie Klein invited us into the phenomenology of the schizoid dilemma through
her depictions of the paranoid-schizoid position. By inserting his recursive
arrows, Bion extended this conceptualization, showing us the folly of believing
that we can ever entirely move beyond the frightening fantasies and realities of
social exclusion and isolation. The 21st century has brought, along with the
explosion of technology, an expulsion from the social order of many children who
have found refuge from isolation and humiliation in the more accessible and less
terrifying world of media and technological invention. What may look like
narcissism can mask a terrible underlying schizoid failure to enter into the
human race. This is the realm of fantasy run amok, where desire becomes alien and
alienated such that one is haunted and hunted down by its very possibility. In
this universe, conceptualizations from Klein, Bion, and Lacan help us to locate
the individual who has become caught in a massive psychic retreat such that there
is no subject because there are no objects. To illustrate, I describe my work
with a young man who is living in a terrible "zombie zone" where people are not
real and therefore are incomprehensible and terribly dangerous. The poignancy of
his dilemma is heartbreaking. Perhaps that is one lesson we can still take from
our old fairy tales: when one's heart can be broken by another's plight, then
comes the possibility of a healing, an entry through that piercing of what had
been impenetrable.
PMID- 25117782
TI - Why, Mrs. Robinson? The seduction of teenage boys by women in classic films.
AB - Utilizing three classic films, and psychoanalytic developmental theory, this
paper explores the conscious and unconscious reasons why older women become
sexually involved with teenage boys. After a presentation of aspects of young
adult and midlife female development and a psychodynamic explanation for the
developmental similarities between adolescence and menopause, each of the three
films is summarized. The dynamics behind the women's behavior, as presented in
the films, are discussed. The third section of the paper discusses similarities
and differences among the three women and the negative effects on the boys'
development.
PMID- 25117779
TI - Molecular basis and genetic predisposition to intracranial aneurysm.
AB - Intracranial aneurysms, also called cerebral aneurysms, are dilatations in the
arteries that supply blood to the brain. Rupture of an intracranial aneurysm
leads to a subarachnoid hemorrhage, which is fatal in about 50% of the cases.
Intracranial aneurysms can be repaired surgically or endovascularly, or by
combining these two treatment modalities. They are relatively common with an
estimated prevalence of unruptured aneurysms of 2%-6% in the adult population,
and are considered a complex disease with both genetic and environmental risk
factors. Known risk factors include smoking, hypertension, increasing age, and
positive family history for intracranial aneurysms. Identifying the molecular
mechanisms underlying the pathogenesis of intracranial aneurysms is complex.
Genome-wide approaches such as DNA linkage and genetic association studies, as
well as microarray-based mRNA expression studies, provide unbiased approaches to
identify genetic risk factors and dissecting the molecular pathobiology of
intracranial aneurysms. The ultimate goal of these studies is to use the
information in clinical practice to predict an individual's risk for developing
an aneurysm or monitor its growth or rupture risk. Another important goal is to
design new therapies based on the information on mechanisms of disease processes
to prevent the development or halt the progression of intracranial aneurysms.
PMID- 25117783
TI - Emotions and cognitions: a critique of the dichotomous view of mental function.
AB - Many approaches to the psyche, models of therapy, and neuroscience tend to view
emotional and cognitive brain functions as separate entities. Such a focus on one
of these two aspects of mental function, at times comes at the expense of
ignoring the other. In this paper emotions and cognitions, along with perceptions
and other elements of the internal and external contexts, are viewed as relevant
vectors in a matrix of information. Through the processes of pattern completion
and noise reduction, information in each of these vectors may evoke memories in
the same or other vectors that are used in the formation of a subjective
understanding of each experience. The important roles of the external (physical,
temporal, relevant events, etc.) and internal (emotional, affective, hormonal,
medications, etc.) contexts in the formation of such subjective experiences will
be discussed. The use of this view in broader and more comprehensive
psychotherapeutic approaches and combined pharmacological and psychological
treatment is explored.
PMID- 25117784
TI - The centrality of guilt: working with ultra-orthodox Jewish patients in Israel.
AB - The ultra-orthodox Jewish (Haredi) community in Israel is characterized by strict
observance of the requirements of orthodox Jewish life. Psychoanalytic
psychotherapy within this community brings us into contact with guilt as a
central emotion throughout the therapeutic process. The exposure to new concepts,
ways of thought and a previously unknown space, together with increased awareness
of internal wishes and drives, are experienced as forbidden areas that arouse an
awakening of conscience and a sense of guilt. The author's cases illustrate these
conflicts.
PMID- 25117780
TI - Serum 25-hydroxyvitamin D and cognitive decline in the very old: the Newcastle
85+ Study.
AB - BACKGROUND AND PURPOSE: Studies investigating the association between 25
hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking.
METHODS: Cross-sectional (baseline) and prospective data (up to 3 years follow
up) from 775 participants in the Newcastle 85+ Study were analysed for global
(measured by the Standardized Mini-Mental State Examination) and attention
specific (measured by the attention battery of the Cognitive Drug Research test)
cognitive performance in relation to season-specific 25(OH)D quartiles. RESULTS:
Those in the lowest and highest season-specific 25(OH)D quartiles had an
increased risk of impaired prevalent (1.66, 95% confidence interval 1.06-2.60, P
= 0.03; 1.62, 95% confidence interval 1.02-2.59, P = 0.04, respectively) but not
incident global cognitive functioning or decline in functioning compared with
those in the middle quartiles adjusted for sociodemographic, health and lifestyle
confounders. Random effects models showed that participants belonging to the
lowest and highest 25(OH)D quartiles, compared with those in the middle
quartiles, had overall slower (log-transformed) attention reaction times for
Choice Reaction Time (lowest, beta = 0.023, P = 0.01; highest, beta = 0.021, P =
0.02), Digit Vigilance Task (lowest, beta = 0.009, P = 0.05; highest, beta =
0.01, P = 0.02) and Power of Attention (lowest, beta = 0.017, P = 0.02; highest,
beta = 0.022, P = 0.002) and greater Reaction Time Variability (lowest, beta =
0.021, P = 0.02; highest, beta = 0.02, P = 0.03). The increased risk of worse
global cognition and attention amongst those in the highest quartile was not
observed in non-users of vitamin D supplements/medication. CONCLUSION: Low and
high season-specific 25(OH)D quartiles were associated with prevalent cognitive
impairment and poorer overall performance in attention-specific tasks over 3
years in the very old, but not with global cognitive decline or incident
impairment.
PMID- 25117785
TI - Agency, surrender (and grace) in the psychoanalytic process.
PMID- 25117786
TI - Psychoanalysis: the sacred and the profane.
PMID- 25117792
TI - A comparison of the effects of desflurane versus propofol on transcranial motor
evoked potentials in pediatric patients.
AB - PURPOSE: The aim was to compare the effects of propofol and desflurane anesthesia
on transcranial motor evoked potentials (MEPs) from pediatric patients undergoing
surgery for spinal deformities. METHODS: Desflurane and propofol cohorts (25
patients each) were obtained retrospectively and matched for patient
characteristics and surgical approach. MEPs from the thenar eminence and abductor
hallucis were compared during maintenance anesthesia on desflurane (0.6-0.8 MAC)
or propofol infusion (150-300 MUg/kg/min). MEP amplitudes and durations were
obtained for successive 30-min intervals for 150 min, beginning 60 min after
maintenance anesthesia. RESULTS: Mean peak to peak amplitudes of MEPs under
desflurane anesthesia from the thenar eminence (419 MUV) and abductor hallucis
(386 MUv) were not significantly different from those under propofol (608 MUV,
343 MUV, thenar, and abductor hallucis, respectively). Stimulation was greater by
42 V and 136 mA, and trains were slightly longer in the desflurane compared to
the propofol group (p < 0.05). Most MEP amplitudes for the desflurane and
propofol cohorts remained the same or increased (71 % of cases) when those after
150 min were compared to those in the first 30-min interval. CONCLUSIONS: MEPs
with good amplitudes were obtained under desflurane only anesthesia that were
comparable to propofol only anesthesia in pediatric patients during surgery for
spinal deformities. There was no evidence for anesthetic fade over the time
period examined. When used by itself, desflurane can be considered a viable
alternative to propofol anesthesia.
PMID- 25117793
TI - Staff-resident interactions in long-term care for people with dementia: the role
of meeting psychological needs in achieving residents' well-being.
AB - OBJECTIVES: The aim of this study is to explore the extent to which staff
resident interactions address or undermine residents' psychological needs and how
such interactions are associated with residents' well-being. METHOD: Data on
staff-resident interactions and residents' well-being were collected for 51
residents from nine long-term care settings using dementia care mapping (DCM).
DCM yields a count and detailed description of staff-resident interactions that
either address (personal enhancers - PEs) or undermine (personal detractions -
PDs) residents' psychological needs, and every 5-minute scores for each
resident's mood and engagement (ME-value). The relationship between PEs and PDs
and well-being was analysed by studying residents' ME-values before and three
time frames after a PE or PD occurred. RESULTS: A total of 76 PEs and 33 PDs were
observed. The most common PEs were those addressing psychological needs for
comfort and occupation. However residents' well-being increased most often after
PEs that addressed residents' need for identity, attachment and inclusion. The
most common PDs were those which undermined the need for comfort, inclusion and
occupation. Residents' well-being decreased most often after PDs that undermined
the need for comfort. CONCLUSION: Increasing interactions which address
residents' need for attachment, identity and inclusion and eliminating
interactions which undermine residents' need for comfort may be particularly
important in achieving residents' well-being. In the long run, residents' well
being could be achieved by staff availing of the opportunities to empower and
facilitate residents, thus meeting their needs for occupation. These findings
provide directions for training in person-centred care.
PMID- 25117794
TI - Influence of KIR genes and their HLA ligands in the pathogenesis of leprosy in a
hyperendemic population of Rondonopolis, Southern Brazil.
AB - BACKGROUND: The objective of this study was to investigate the association
between KIR genes and the immunopathogenesis of leprosy. METHODS: The types of
KIR and HLA genes were evaluated by PCR-SSOP-Luminex in 408 patients with leprosy
and 413 healthy individuals. Statistical analysis was performed using the Chi
square or Fisher's exact test and stepwise multivariate analysis. RESULTS: There
was a higher frequency of activating KIR genes (KIR2DS1, 2DS2 and 3DS1) together
with their HLA ligands in the tuberculoid (TT) group as compared to the
lepromatous leprosy (LL) group. KIR2DL2/2DL2-C1 was more frequent in the patient,
TT and LL groups than in the control group. Borderline patients presented a
higher frequency of inhibitory pairs when compared to the control group, and a
higher frequency of activating pairs as compared to the LL group. Multivariate
analysis confirmed the associations and demonstrated that being a female is a
protective factor against the development of the disease per se and the more
severe clinical form. CONCLUSIONS: This study showed that activating and
inhibitory KIR genes may influence the development of leprosy - in particular,
activating genes may protect against the more aggressive form of the disease -
thereby demonstrating the role of NK cells in the immunopathology of the disease.
PMID- 25117795
TI - A short peptide from frog skin accelerates diabetic wound healing.
AB - Delayed wound healing will result in the development of chronic wounds in some
diseases, such as diabetes. Amphibian skins possess excellent wound-healing
ability and represent a resource for prospective wound-healing promoting
compounds. A potential wound-healing promoting peptide (CW49; amino acid sequence
APFRMGICTTN) was identified from the frog skin of Odorrana grahami. It promotes
wound healing in a murine model with a full-thickness dermal wound in both normal
and diabetic animals. In addition to its strong angiogenic ability with respect
to the upregulation of some angiogenic proteins, CW49 also showed a significant
anti-inflammatory effect in diabetic wounds, which was very important for healing
chronic wounds. CW49 had little effect on re-epithelialization, resulting in no
significant effect on wound closure rate compared to a vehicle control.
Altogether, this indicated that CW49 might accelerate diabetic wound healing by
promoting angiogenesis and preventing any excessive inflammatory response.
Considering its favorable traits as a small peptide that significantly promotes
angiogenesis, CW49 might be an excellent candidate or template for the
development of a drug for use in the treatment of diabetic wounds.
PMID- 25117797
TI - The selective adsorption of tellurium in the aluminosilicate regions of AFI- and
MOR-type microporous crystals.
AB - Attempts have been made to load tellurium (Te) atoms into the one-dimensional
nano-channels of microporous crystals of aluminophosphate AlPO4-5 and of
aluminosilicate mordenites of the Na(+) form (Na-MOR) and the H(+)-form (H-MOR)
at 673 K. The density of the atoms adsorbed was in the sequence 0 ~ AlPO4-5 ? H
MOR < Na-MOR. AlPO4-5 provides a shallow potential of periodical charge
fluctuation for Te atoms, from the alternate ordering of Al and P atoms through O
atoms. Mordenite offers a sufficiently strong potential for Te adsorption, but
the magnitude varies with the type of cation. Dipoles between framework AlO2(-)
anion sites and their Na(+) counter-ions in Na-MOR provide a stronger potential
than the Bronsted acid points in H-MOR. The adsorption of Te atoms in the silico
aluminophosphate SAPO-5 was between that of AlPO4-5 and H-MOR, leading us to
suspect that Te atoms are selectively adsorbed in the aluminosilicate regions
accompanying the Bronsted acid points distributed in the major aluminophosphate
network. The aluminosilicate regions in SAPO-5 are below 500 nm in size and are
distributed throughout a single crystal.
PMID- 25117796
TI - Pharmacological characterisation of the mechanisms underlying the relaxant effect
of adrenomedullin in the rat carotid artery.
AB - OBJECTIVES: We investigated the mechanisms underlying the relaxant effect of
adrenomedullin (AM) in the rat carotid artery and verified the expression of AM
system components in this tissue. METHODS: The carotid artery was isolated from
male Wistar rats and immunohistochemical, Western immunoblotting, real-time
polymerase chain reaction and functional assays were conducted. KEY FINDINGS:
Protein and mRNA expression of AM, calcitonin receptor-like receptor (CRLR) and
receptor activity-modifying proteins (RAMP)1, 2, 3 were detected in carotid
segments from male Wistar rats. Immunohistochemical assays showed that AM and
CRLR receptors are expressed in the endothelium and smooth muscle cells.
Functional assays showed that AM concentration dependently relaxed carotid rings
with intact endothelium. Endothelial removal reduced, but not abolished, the
relaxation induced by AM. AM22-52 (selective antagonist for AM receptors) and
calcitonin gene-related peptide (CGRP)8-37 (selective CGRP receptor antagonist)
reduced AM-induced relaxation in endothelium-intact rings. Pre-incubation of
endothelium-intact rings with N-nitro-L-arginine methyl ester, 1H
[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one or Rp-8-Bromo-?-phenyl-1,N2
ethenoguanosine 3',5'cyclic monophosphorothioate reduced AM-induced relaxation.
Inhibition of cyclooxygenase-1 and protein kinase A (PKA) reduced AM-induced
relaxation. The relaxation induced by AM was attenuated by the K(+) channel
blockers apamin and glibenclamide. AM increased nitrate levels and 6-keto
prostaglandin F1alpha (stable product of prostacyclin) in the rat carotid. In
endothelium-denuded rings, AM22-52 , glibenclamide and PKA inhibition by H89
reduced AM-induced relaxation. CONCLUSIONS: The novelty of this work is that it
first demonstrated functionally that AM-induced relaxation is mediated by AM and
CGRP receptors located on the endothelium and AM receptors located on smooth
muscle of rat carotid arteries. AM-induced relaxation involves the nitric oxide
cGMP pathway, a vasodilator prostanoid, the opening of K(+) channels and the
activation of PKA.
PMID- 25117799
TI - Recent developments in the search for a cure for HIV-1 infection: targeting the
latent reservoir for HIV-1.
AB - HIV-1 infection can now be readily controlled with combination antiretroviral
therapy. However, the virus persists indefinitely in a stable latent reservoir in
resting CD4(+) T cells. This reservoir generally prevents cure of the infection
with combination antiretroviral therapy alone. However, several recent cases of
potential HIV-1 cure have generated renewed optimism. Here we review these cases
and consider new developments in our understanding of the latent reservoir. In
addition, we consider clinical aspects of curative strategies to provide a more
realistic picture of what a generally applicable cure for HIV-1 infection is
likely to entail.
PMID- 25117800
TI - Cure of HIV infection: is the long wait over?
PMID- 25117798
TI - Progress in HIV-1 vaccine development.
AB - The past 2 years have seen a number of basic and translational science advances
in the quest for development of an effective HIV-1 vaccine. These advances
include discovery of new envelope targets of potentially protective antibodies,
demonstration that CD8(+) T cells can control HIV-1 infection, development of
immunogens to overcome HIV-1 T-cell epitope diversity, identification of
correlates of transmission risk in an HIV-1 efficacy trial, and mapping of the
coevolution of HIV-1 founder envelope mutants in infected subjects with broad
neutralizing antibodies, thereby defining broad neutralizing antibody
developmental pathways. Despite these advances, a promising HIV-1 vaccine
efficacy trial published in 2013 did not prevent infection, and the HIV-1 vaccine
field is still years away from deployment of an effective vaccine. This review
summarizes what some of the scientific advances have been, what roadblocks still
remain, and what the most promising approaches are for progress in design of
successful HIV-1 vaccine candidates.
PMID- 25117802
TI - Prenatal adverse life events increase the risk for atopic diseases in children,
which is enhanced in the absence of a maternal atopic predisposition.
AB - BACKGROUND: There is evidence to suggest an association between prenatal maternal
stress and the development of asthma or other atopic diseases in offspring. Yet,
insights on the lasting effect of multiple, common prenatal stressors are rare,
and the effects of prenatal timing are poorly understood. Further, it remains
elusive if prenatal life events modify the risk for atopic diseases in the
context of a parental predisposition to atopy. OBJECTIVE: We tested whether
women's experiences of common, adverse life events during the first or second
half of pregnancy predicted the risk of developing atopic diseases in their
children and whether a reported parental atopic disease moderated this
association. METHODS: We calculated the odds of a child developing asthma,
eczema, and/or allergic rhinitis at ages 6 or 14 years, depending on maternal
prenatal exposure to negative life events in a sample of 1587 children from the
Western Australian Pregnancy Cohort (Raine) Study by using multivariable logistic
regression. RESULTS: We observed that the likelihood of asthma and eczema at age
14 years was significantly increased in children of mothers who had experienced
adverse life events during the second half of gestation (1 life event: adjusted
odds ratio for asthma, 2.08 [95% CI, 1.22-3.54]). A stronger increase in the odds
to develop asthma upon prenatal life events was present in children of mothers
without asthma compared with mothers with asthma. CONCLUSIONS: Maternal adverse
life events during the second half of gestation are linked to an increased risk
for the development of atopic disorders, asthma, and eczema, in the case of
asthma, particularly in the absence of a maternal asthma.
PMID- 25117803
TI - Successful RAG1-SCID gene therapy depends on the level of RAG1 expression.
PMID- 25117804
TI - Reply: To PMID 24332219.
PMID- 25117805
TI - Study design and protocol for a theory-based behavioral intervention focusing on
maintenance of weight loss: the Maintenance After Initiation of Nutrition
TrAINing (MAINTAIN) study.
AB - BACKGROUND: Obesity is a significant public health problem. Although various
lifestyle approaches are effective for inducing significant weight loss, few
effective behavioral weight maintenance strategies have been identified. It has
been proposed that behavior maintenance is a distinct state that involves
different psychological processes and behavioral skills than initial behavior
change. Previously, we created a conceptual model that distinguishes behavior
initiation from maintenance. This model was used to generate Maintenance After
Initiation of Nutrition TrAINing (MAINTAIN), an intervention to enhance weight
loss maintenance following initiation. The effectiveness of MAINTAIN is being
evaluated in an ongoing trial, the rationale and procedures of which are reported
herein. METHODS/DESIGN: Veterans aged <= 75 with body mass index >= 30 kg/m(2)
participate in a 16-week, group-based weight loss program. Participants who lose
>= 4 kg by the end of 16 weeks (target n = 230) are randomized 1:1 to receive (a)
usual care for 56 weeks or (b) MAINTAIN, a theoretically-informed weight loss
maintenance intervention for 40 weeks, followed by 16 weeks of no intervention
contact. MAINTAIN involves 3 in-person group visits that transition to 8
individualized telephone calls with decreasing contact frequency. MAINTAIN
focuses on satisfaction with outcomes, weight self-monitoring, relapse
prevention, and social support. We hypothesize that, compared to usual care,
MAINTAIN will result in at least 3.5 kg less regain and better relative levels of
caloric intake and physical activity over 56 weeks, and that it will be cost
effective. DISCUSSION: If effective, MAINTAIN could serve as a model for
redesigning existing weight loss programs. CLINICALTRIALSGOV IDENTIFIER:
NCT01357551.
PMID- 25117806
TI - A protocol to evaluate the efficacy, perceptions, and cost of a cholesterol
packaging approach to improve medication adherence.
AB - PURPOSE: Elevated low-density lipoprotein cholesterol (LDL-C) is a major
modifiable risk factor for cardiovascular disease (CVD), a leading cause of death
in the United States. Despite clinical practice guidelines aimed at facilitating
LDL-C control, many Veterans do not achieve guideline-recommended LDL-C levels.
METHODS: We describe a study focused on VA healthcare system users at risk for
CVD (i.e., LDL-C level >130 mg/dl and/or <80% cholesterol pill refill adherence
in the last 12 months). We are conducting a two and a half year randomized
controlled trial (i.e., intervention administered over 12 months) among Veterans
with uncontrolled cholesterol receiving care at select VA-affiliated primary care
clinics in North Carolina. We anticipate enrolling 250 diverse patients (10%
women; 40% African American). Patients are randomized to an educational control
group or intervention group. Intervention group participants' medication is
provided in special blister packaging labeled for daily use that includes
reminders; MeadWestvaco Corporation's pre-filled DosePak(r) contains standard
doses of statins in accordance with the existing prescriptions. CONCLUSIONS: Pre
filled blister packaging may provide an inexpensive solution to improve
medication adherence. Our study enrolls a diverse sample and provides information
about whether an adherence packaging intervention can: 1) improve medication
adherence; 2) improve patients' LDL-C levels; 3) be well received by patients and
providers; and 4) provide a cost effective solution to improve medication
adherence.
PMID- 25117807
TI - Lack of association between leptin levels and leptin gene polymorphism in obese
women.
AB - The aim of the present study was to evaluate the relationship between
oligopolymorphism in the 25th codon of leptin gene and obesity. Eighty-seven
obese women and 75 healthy women were constituted obese and control groups. Body
fat percent, fat mass and lean body mass were determined by bioimpedance meter
and leptin levels were determined. The presence of 25th codon oligopolymorphism
in the leptin gene was done by PCR-RFLP technique. Mean leptin levels were 38.5+/
22.0 ng/ml, and 147.9+/-44.8 ng/ml in the control and obese groups, respectively.
The correlations of serum leptin level to body fat percentage and fat mass in the
control group were significant. The correlations in the obese group were not
significant. This data implies that the difference of leptin levels between
control and obese groups are more likely to be associated with alterations in the
leptin gene other than 25th codon or alterations in the leptin receptor gene.
PMID- 25117808
TI - Pretherapeutic gamma-glutamyltransferase is an independent prognostic factor for
patients with renal cell carcinoma.
AB - BACKGROUND: Gamma-glutamyltransferase (GGT) regulates apoptotic balance and
promotes cancer progression and invasion. Higher pretherapeutic GGT serum levels
have been associated with worse outcomes in various malignancies, but there are
no data for renal cell carcinoma (RCC). METHODS: Pretherapeutic GGT serum levels
and clinicopathological parameters were retrospectively evaluated in 921
consecutive RCC patients treated with nephrectomy at a single institution between
1998 and 2013. Gamma-glutamyltransferase was analysed as continuous and
categorical variable. Associations with RCC-specific survival were assessed with
Cox proportional hazards models. Discrimination was measured with the C-index.
Decision-curve analysis was used to evaluate the clinical net benefit. The median
postoperative follow-up was 45 months. RESULTS: Median pretherapeutic serum GGT
level was 25 U l(-1). Gamma-glutamyltransferase levels increased with advancing T
(P<0.001), N (P=0.006) and M stages (P<0.001), higher grades (P<0.001), and
presence of tumour necrosis (P<0.001). An increase of GGT by 10 U l(-1) was
associated with an increase in the risk of death from RCC by 4% (HR 1.04,
P<0.001). Based on recursive partitioning-based survival tree analysis, we
defined four prognostic categories of GGT: normal low (<17.5 U l(-1)), normal
high (17.5 to <34.5 U l(-1)), elevated (34.5 to <181.5 U l(-1)), and highly
elevated (?181.5 U l(-1)). In multivariable analyses that adjusted for the effect
of standard features, both continuously and categorically coded GGT were
independent prognostic factors. Adding GGT to a model that included standard
features increased the discrimination by 0.9% to 1.8% and improved the clinical
net benefit. CONCLUSIONS: Pretherapeutic serum GGT is a novel and independent
prognostic factor for patients with RCC. Stratifying patients into prognostic
subgroups according to GGT may be used for patient counselling, tailoring
surveillance, individualised treatment planning, and clinical trial design.
PMID- 25117809
TI - Guidelines for the use of cell lines in biomedical research.
AB - Cell-line misidentification and contamination with microorganisms, such as
mycoplasma, together with instability, both genetic and phenotypic, are among the
problems that continue to affect cell culture. Many of these problems are
avoidable with the necessary foresight, and these Guidelines have been prepared
to provide those new to the field and others engaged in teaching and instruction
with the information necessary to increase their awareness of the problems and to
enable them to deal with them effectively. The Guidelines cover areas such as
development, acquisition, authentication, cryopreservation, transfer of cell
lines between laboratories, microbial contamination, characterisation,
instability and misidentification. Advice is also given on complying with current
legal and ethical requirements when deriving cell lines from human and animal
tissues, the selection and maintenance of equipment and how to deal with problems
that may arise.
PMID- 25117810
TI - Senescent cancer-associated fibroblasts secrete active MMP-2 that promotes
keratinocyte dis-cohesion and invasion.
AB - BACKGROUND: Previous studies have demonstrated that senescent cancer-associated
fibroblasts (CAFs) derived from genetically unstable oral squamous cell
carcinomas (GU-OSCC), unlike non-senescent CAFs from genetically stable
carcinomas (GS-OSCC), promoted keratinocyte invasion in vitro in a paracrine
manner. The mechanism by which this occurs is unclear. METHODS: Previous work to
characterise the senescent-associated secretory phenotype (SASP) has used
antibody arrays, technology that is limited by the availability of suitable
antibodies. To extend this work in an unbiased manner, we used 2D gel
electrophoresis and mass spectroscopy for protein identification. Matrix
metalloproteinases (MMPs) were investigated by gelatin zymography and western
blotting. Neutralising antibodies were used to block key molecules in the
functional assays of keratinocyte adhesion and invasion. RESULTS: Among a variety
of proteins that were differentially expressed between CAFs from GU-OSCC and GS
OSCC, MMP-2 was a major constituent of senescent CAF-CM derived from GU-OSCC. The
presence of active MMP-2 was confirmed by gelatine zymography. MMP-2 derived from
senescent CAF-CM induced keratinocyte dis-cohesion and epithelial invasion into
collagen gels in a TGF-beta-dependent manner. CONCLUSIONS: Senescent CAFs from GU
OSCC promote a more aggressive oral cancer phenotype by production of active MMP
2, disruption of epithelial adhesion and induction of keratinocyte invasion.
PMID- 25117811
TI - MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and
stemness in pancreatic cancer.
AB - BACKGROUND: Pancreatic cancer has a poor prognosis because of its high
refractoriness to chemotherapy and tumour recurrence, and these properties have
been attributed to cancer stem cells (CSCs). MicroRNA (miRNA) regulates various
molecular mechanisms of cancer progression associated with CSCs. This study aimed
to identify the candidate miRNA and to characterise the clinical significance.
METHODS: We established gemcitabine-resistant Panc1 cells, and induced CSC-like
properties through sphere formation. Candidate miRNAs were selected through
microarray analysis. The overexpression and knockdown experiments were performed
by evaluating the in vitro cell growth and in vivo tumourigenicity. The
expression was studied in 24 pancreatic cancer samples after laser captured
microdissection and by immunohistochemical staining. RESULTS: The in vitro drug
sensitivity of pancreatic cancer cells was altered according to the miR-1246
expression via CCNG2. In vivo, we found that miR-1246 could increase tumour
initiating potential and induced drug resistance. A high expression level of miR
1246 was correlated with a worse prognosis and CCNG2 expression was significantly
lower in those patients. CONCLUSIONS: miR-1246 expression was associated with
chemoresistance and CSC-like properties via CCNG2, and could predict worse
prognosis in pancreatic cancer patients.
PMID- 25117812
TI - Plasma microRNA profiles: identification of miR-25 as a novel diagnostic and
monitoring biomarker in oesophageal squamous cell carcinoma.
AB - BACKGROUND: Recent studies have demonstrated that microRNAs are stably detectable
in plasma/serum because of their binding to specific proteins or being packaged
in secretory particles. This study was designed to detect novel microRNAs in
plasma for cancer detection and monitoring using microRNA array-based approaches
in oesophageal squamous cell carcinoma (ESCC) patients. METHODS: Through the
integration of two Toray 3D-Gene microRNA array-based approaches to compare
plasma microRNA levels between ESCC patients and healthy volunteers and between
preoperative and postoperative ESCC patients, we identified a novel plasma
biomarker in ESCC. RESULTS: (1) Eight upregulated and common microRNAs (miR-15b,
16, 17, 25, 19b, 20a, 20b, and 106a) were selected using two high-resolution
microRNA array approaches. (2) Test-scale analyses by quantitative RT-PCR
validated a significant higher levels of plasma miR-19b (P=0.0020) and miR-25
(P=0.0030) in ESCC patients than controls. However, a significant correlation was
observed between plasma miR-19b levels and concentrations of red blood cells
(P=0.0073) and haemoglobin (P=0.0072). (3) miR-25 expression was found to be
significantly higher in ESCC tissues (P=0.0157) and ESCC cell lines (P=0.0093)
than in normal tissues and fibroblasts. (4) In a large-scale validation analysis,
plasma miR-25 levels were significantly higher in 105 preoperative (P<0.0001)
ESCC patients who underwent curative oesophagectomy and 20 superficial ESCC
patients who underwent endoscopic resection (P<0.0001) than in 50 healthy
volunteers. (5) Plasma miR-25 levels were significantly reduced in postoperative
samples than in preoperative samples (P<0.0005) and were significantly increased
during ESCC recurrences (P=0.0145). CONCLUSIONS: Plasma miR-25 might be a
clinically useful biomarker for cancer detection and the monitoring of tumour
dynamics in ESCC patients.
PMID- 25117813
TI - The lag time in initiating clinical testing of new drugs in combination with
radiation therapy, a significant barrier to progress?
AB - BACKGROUND: The clinical development of new drugs with radiation appears to be
limited. We hypothesised that phase I clinical trials with radiation therapy (RT)
are initiated too late into a new drug's lifetime, impeding the ability to
complete RT-drug development programmes before patent expiration. METHODS: We
identified novel drug-radiation phase I combination trials performed between 1980
and 2012 within the PubMed and ClinicalTrials.gov databases. Data gathered for
each drug included: date the initial phase I trial with/without RT was
opened/published, date of the published positive phase III trials, and patent
expiration dates. Lag time was defined as the interval between opening of the
phase I trial without RT and the opening of the phase I with RT. Linear
regression was used to model how the lag time has changed over time. RESULTS: The
median lag time was 6 years. The initial phase I trial with RT was typically
published 2 years after the first published positive phase III trial and 11 years
before patent expiration. Using a best-fit linear model, lag time decreased from
10 years for phase I trials published in 1990 to 5 years in 2005 (slope
significantly non-zero, P<0.001). CONCLUSIONS: Clinical drug development with RT
commences late in the life cycle of anti-cancer agents. Taking into account the
additional time required for late-phase clinical trials, the delay in initiating
clinical testing of drug-RT combinations discourages drug companies from further
pursuing RT-based development. Encouragingly, lag time appears to be decreasing.
Further reduction in lag time may accelerate RT-based drug development,
potentially improving patient outcomes.
PMID- 25117814
TI - Fascin is involved in the chemotherapeutic resistance of breast cancer cells
predominantly via the PI3K/Akt pathway.
AB - BACKGROUND: A major therapeutic challenge for breast cancer is the ability of
cancer cells to evade killing of conventional chemotherapeutic agents. We have
recently reported the actin-bundling protein (fascin) as a major regulator of
breast cancer metastasis and survival. METHODS: Survival of breast cancer
patients that received chemotherapy and xenograft tumour model was used to assess
the effect of chemotherapy on fascin-positive and -negative breast cancer cells.
Molecular and cellular assays were used to gain in-depth understanding of the
relationship between fascin and chemoresistance. RESULTS: We showed a significant
correlation between fascin expression and shorter survival in breast cancer
patients who received chemotherapy. In xenograft experiments, fascin-positive
cancer cells displayed significantly more resistance to chemotherapy-mediated
apoptotic cell death than fascin-negative counterparts. This increased
chemoresistance was at least partially mediated through PI3K/Akt signalling, and
was paralleled by increased FAK phosphorylation, enhanced expression of the
inhibitor of apoptosis proteins (XIAP and Livin) and suppression of the
proapoptotic markers (caspase 9, caspase 3 and PARP). CONCLUSIONS: This is the
first report to demonstrate fascin involvement in breast cancer chemotherapeutic
resistance, supporting the development of fascin-targeting drugs for better
treatment of chemoresistance breast cancer.
PMID- 25117815
TI - Identification of 33 candidate oncogenes by screening for base-specific
mutations.
AB - BACKGROUND: Genes with recurrent codon-specific somatic mutations are likely
drivers of tumorigenesis and potential therapeutic targets. Hypermutable cancers
may represent a sensitive system for generation and selection of oncogenic
mutations. METHODS: We utilised exome-sequencing data on 25 sporadic
microsatellite-instable (MSI) colorectal cancers (CRCs) and searched for base
specific somatic mutation hotspots. RESULTS: We identified novel mutation
hotspots in 33 genes. Fourteen genes displayed mutations in the validation set of
254 MSI CRCs: ANTXR1, MORC2, CEP135, CRYBB1, GALNT9, KRT82, PI15, SLC36A1, CNTF,
GLDC, MBTPS1, OR9Q2, R3HDM1 and TTPAL. A database search found examples of the
hotspot mutations in multiple cancer types. CONCLUSIONS: This work reveals a
variety of new recurrent candidate oncogene mutations to be further scrutinised
as potential therapeutic targets.
PMID- 25117817
TI - EGFR expression is associated with decreased benefit from trastuzumab in the
NCCTG N9831 (Alliance) trial.
AB - BACKGROUND: Epidermal growth factor receptor (EGFR) has been hypothesised to
modulate the effectiveness of anti-HER2 therapy. We used a standardised,
quantitative immunofluorescence assay and a novel EGFR antibody to evaluate the
correlation between EGFR expression and clinical outcome in the North Central
Cancer Treatment Group (NCCTG) N9831 trial. METHODS: Tissue microarrays were
constructed that allowed analysis of 1365 patients randomly assigned to receive
chemotherapy alone (Arm A), sequential trastuzumab after chemotherapy (Arm B) and
chemotherapy with concurrent trastuzumab (Arm C). Measurement of EGFR was
performed using the EGFR antibody, D38B1, on the fluorescence-based AQUA
platform. The result was validated using an independent retrospective metastatic
breast cancer cohort (n=130). RESULTS: Epidermal growth factor receptor assessed
as a continuous (logarithmic transformed) variable shows an association with
disease-free survival in Arm C (P=0.009) but not in Arm A or B. High EGFR
expression was associated with worse outcome (Hazard ratio (HR)=2.15; 95% CI 1.28
3.60, P=0.004). Validation in a Greek metastatic breast cancer cohort showed an
HR associated with high EGFR expression of 1.92 (P=0.0073). CONCLUSIONS: High
expression of EGFR appears to be associated with decreased benefit from adjuvant
concurrent trastuzumab. Since other treatment options exist for HER2-driven
tumours, further validation of these data may select patients for alternative or
additive therapy.
PMID- 25117816
TI - Coexistence of KRAS mutation with mutant but not wild-type EGFR predicts response
to tyrosine-kinase inhibitors in human lung cancer.
PMID- 25117818
TI - Risk of leukaemia or cancer in the central nervous system among children living
in an area with high indoor radon concentrations: results from a cohort study in
Norway.
AB - BACKGROUND: Over the past few years, there has been growing interest in assessing
the relationship between exposure to radon at home and the risk of childhood
cancer. Previous studies have produced conflicting results, probably because of
limitations assessing radon exposure, too few cancer cases and poorly documented
health statistics. METHODS: We used a cohort approach of 0-15-year-old children
to examine whether residential radon exposure was associated with childhood
leukaemia and cancer in the central nervous system in the Oslo region. The study
was based on Norwegian population registers and identified cancer cases from The
Cancer Registry of Norway. The residence of every child was geo-coded and
assigned a radon exposure. RESULTS: In all, 712 674 children were followed from
1967 to 2009 from birth to date of cancer diagnosis, death, emigration or 15
years of age. A total of 864 cancer cases were identified, 437 children got
leukaemia and 427 got cancer in the central nervous system.Conclusions or
interpretation:No association was found for childhood leukaemia. An elevated
nonsignificant risk for cancer in the central nervous system was observed. This
association should be interpreted with caution owing to the crude exposure
assessment and possibilities of confounding.
PMID- 25117819
TI - BRAF(V600E) melanoma cells secrete factors that activate stromal fibroblasts and
enhance tumourigenicity.
AB - BACKGROUND: Melanoma, the most lethal form of skin cancer, is responsible for
over 80% of all skin cancer deaths and is highly metastatic, readily spreading to
the lymph nodes or metastasising to other organs. The frequent genetic mutation
found in metastatic melanoma, BRAF(V600E), results in constitutive activation of
the mitogen-activated protein kinase pathway. METHODS: In this study, we utilised
genetically engineered melanoma cell lines and xenograft mouse models to
investigate how BRAF(V600E) affected cytokine (IL-1beta, IL-6, and IL-8) and
matrix metalloproteinase-1 (MMP-1) expression in tumour cells and in human dermal
fibroblasts. RESULTS: We found that BRAF(V600E) melanoma cells expressed higher
levels of these cytokines and of MMP-1 than wild-type counterparts. Further,
conditioned medium from the BRAF(V600E) melanoma cells promoted the activation of
stromal fibroblasts, inducing expression of SDF-1 and its receptor CXCR4. This
increase was mitigated when the conditioned medium was taken from melanoma cells
treated with the BRAF(V600E) specific inhibitor, vemurafenib. CONCLUSIONS: Our
findings highlight the role of BRAF(V600E) in activating the stroma and suggest a
mechanistic link between BRAF(V600E) and MMP-1 in mediating melanoma progression
and in activating adjacent fibroblasts in the tumour microenvironment.
PMID- 25117821
TI - Hyperfibrinogenemia in appendicitis: a new predictor of perforation in children.
AB - PURPOSE: Acute appendicitis is the most common emergency abdominal inflammation
requiring operation in children. As an acute-phase protein, plasma fibrinogen
always increases with inflammation or tissue necrosis. This had brought about the
assumption that hyperfibrinogenemia in patients with appendicitis may have a
predictive ability for the preoperative diagnosis of appendiceal. Aim of this
retrospective study was to assess the diagnostic value of hyperfibrinogenemia as
a preoperative laboratory marker for appendiceal perforation in children with
acute appendicitis. METHODS: We screened 466 children (168 girls, 298 boys, mean
age, 7.6 years) with histologically confirmed acute appendicitis who received
laparoscopic or open appendectomy between January 2012 and April 2014 in a
pediatric surgery department of an academic teaching hospital. A retrospective
review of the medical records including appendiceal perforation rate and
laboratory results was conducted. RESULTS: Mean plasma fibrinogen level of all
patients was 4.89 g/L (SD 1.74 g/L, range 1.94-15 g/L, median 4.61 mg/dL).
Children with appendiceal perforation had a mean fibrinogen level of 6.18 g/L (SD
1.83 g/L, range 3.02-15 g/L, median 5.79 g/L), which was significantly higher
than those with non-perforated children (P = 0.0001). The specificity of
hyperfibrinogenemia for appendiceal perforation was 0.82 in comparison with 0.25
for white blood count (WBC) and 0.34 for C-reactive protein (CRP). Sensitivity
was 0.74 compared with 0.76 for WBC and 0.94 for CRP. CONCLUSION: Children with
hyperfibrinogenemia and clinical symptoms of appendicitis may be regarded as a
higher risk of appendiceal perforation than whose fibrinogen level is normal.
PMID- 25117822
TI - Astrocytic growth through the autocrine/paracrine production of IL-1beta in the
early infectious phase of fowl glioma-inducing virus.
AB - Fowl glioma is characterized morphologically by multiple nodular astrocytic
growth with disseminated non-suppurative encephalitis. The disease is caused by
fowl glioma-inducing virus (FGV) and its variants, belonging to subgroup A of
avian leukosis virus (ALV-A). Fifty-seven FGV variants have so far been isolated
from Japanese fowls and these variants have a variable degree of glioma
inducibility. However, how these ALVs induce glioma with different degrees and
frequencies has not been fully elucidated. In this study, we investigated the
relationship between intracerebral viral replication and astrocytic growth in the
early infectious phase. Replication abilities of two ALV strains, Sp-53 (a FGV
variant) and ALV-based replication-competent vector RCAS(A) without glioma
inducibility, were compared in the brains of C/O specific pathogen free chickens
at 35 days of age. Sp-53 replicated faster than RCAS(A), and the histological
score and the level of interleukin (IL)-1beta in brains increased depending on
the level of intracerebral viral RNA. Up-regulation of IL-1beta was also
demonstrated in primary cultured astrocytes. These results suggest that the
astrocytic growth in this phase is enhanced through the autocrine/paracrine
production of IL-1beta in the FGV-infected astrocytes.
PMID- 25117823
TI - Association between sleep quality and cardiovascular damage in pre-dialysis
patients with chronic kidney disease.
AB - BACKGROUND: Poor sleep quality, a novel risk factor of cardiovascular diseases
(CVD), is highly prevalent in patients with chronic kidney disease (CKD). The
association between poor sleep quality and cardiovascular damage in patients with
CKD is unclear. This study is aimed to assess the prevalence and related risk
factors of sleep disturbance and determine the relationship between sleep quality
and cardiovascular damage in Chinese patients with pre-dialysis CKD. METHODS: A
total of 427 pre-dialysis CKD patients (mean age = 39 +/- 15 years, 260 male/167
female) were recruited in this study. The demographics and clinical correlates
were collected. The sleep quality was measured by the Pittsburgh Sleep Quality
Index (PSQI), whereas the cardiovascular damage indicators (the Early/late
diastolic peak flow velocity (E/A) ratio and left ventricular mass index (LVMI))
were determined by an echocardiographic examination. RESULTS: Of the CKD
patients, 77.8% were poor sleepers as defined by a PSQI score > 5. Median
estimated glomerular filtration rate (eGFR) was 69.4(15.8-110.9) ml/min/1.73
m(2). Logistic regression analysis revealed that left ventricular hypertrophy
(LVH) was independently associated with the PSQI score (OR = 1.092, 95% CI =
1.011-1.179, p = 0.025), after adjustment for age, sex and clinical systolic
blood pressure, diastolic blood pressure, Phosphate, Intact parathyroid hormone
(iPTH), Hemoglobin and eGFR. The linear regression analysis showed that the E/A
ratios were independently associated with the PSQI score (beta = -0.115, P =
0.028) after adjustment for a series of potential confounding factors.
CONCLUSIONS: Poor sleep quality, which is commonly found in pre-dialysis CKD
patients, is an independent factor associated with cardiovascular damage in CKD
patients. Our finding implies that the association between poor sleep and CVD
might be mediated by cardiac remodeling.
PMID- 25117824
TI - At the second glance: stability of neural responses toward visual sexual stimuli.
AB - INTRODUCTION: Studies investigating the neural responses toward sexual stimuli
can provide an important basis for further understanding disorders of sexual
functioning. Although our knowledge of the neural correlates of sexual stimulus
processing has increased considerably in the last decade, the stability of the
observed effects in studies on neural sexual responses has been rather neglected.
AIMS: The current study aimed to test the stability of behavioral and neural
responses to visual sexual stimuli in men and women over a time span of 1 to 1.5
years. To disentangle valence and arousal-related aspects of sexual stimulus
processing, we employed not only sexual and neutral, but also positive and
negative emotional stimuli. METHODS: A sample of 56 subjects (24 women) was
assessed twice, with an interval of 1 to 1.5 years between assessments. During a
functional magnetic resonance imaging (fMRI) session, participants passively
viewed sexual, neutral, positive, and negative emotional pictures. Pictures were
presented in 24 blocks of five pictures each. Every block was rated immediately
after its presentation with respect to valence, arousal, and sexual arousal. MAIN
OUTCOME MEASURES: Blood oxygen level dependent (BOLD) responses measured by fMRI
and stimulus ratings. RESULTS: fMRI analyses revealed a distributed network
involved in the processing of sexual stimuli, with large parts of this network
being consistently activated at both assessment points. Nucleus accumbens,
anterior cingulate, occipital and parietal cortex showed the most robust results
with respect to group stability. Responses of anterior cingulate, orbitofrontal,
parietal and occipital cortex showed interindividual stability. Gender
differences were restricted to a few regions of interest. CONCLUSIONS: Our data
indicate stability of neural responses toward sexual stimuli not only on the
group but also on the individual level. Activation of parietal and occipital
cortex might reflect a trait like character of attention related responses toward
sexual stimuli.
PMID- 25117820
TI - Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG
2100.
AB - BACKGROUND: Bevacizumab has broad anti-tumour activity, but substantial risk of
hypertension. No reliable markers are available for predicting bevacizumab
induced hypertension. METHODS: A genome-wide association study (GWAS) was
performed in the phase III bevacizumab-based adjuvant breast cancer trial, ECOG
5103, to evaluate for an association between genotypes and hypertension. GWAS was
conducted in those who had experienced systolic blood pressure (SBP) >160 mm Hg
during therapy using binary analysis and a cumulative dose model for the total
exposure of bevacizumab. Common toxicity criteria (CTC) grade 3-5 hypertension
was also assessed. Candidate SNP validation was performed in the randomised phase
III trial, ECOG-2100. RESULTS: When using the phenotype of SBP>160 mm Hg, the
most significant association in SV2C (rs6453204) approached and met genome-wide
significance in the binary model (P=6.0 * 10(-8); OR=3.3) and in the cumulative
dose model (P=4.7 * 10(-8); HR=2.2), respectively. Similar associations with
rs6453204 were seen for CTC grade 3-5 hypertension but did not meet genome-wide
significance. Validation study from ECOG-2100 demonstrated a statistically
significant association between this SNP and grade 3/4 hypertension using the
binary model (P-value=0.037; OR=2.4). CONCLUSIONS: A genetic variant in SV2C
predicted clinically relevant bevacizumab-induced hypertension in two
independent, randomised phase III trials.
PMID- 25117826
TI - Person-to-person transmission of norovirus resulting in an outbreak of acute
gastroenteritis at a summer camp.
AB - BACKGROUND: A significant proportion of norovirus (NV) gastroenteritis outbreaks
described in the Spanish literature have been because of contaminated food or
water. AIM: This study describes an outbreak of acute gastroenteritis because of
NV in which there was person-to-person transmission. MATERIALS AND METHODS: A
retrospective cohort study was carried out; we established the case definition
for primary and secondary cases. An epidemiological survey was designed,
including possible food exposures, and clinical and laboratory data. Water and
stool samples were taken from affected individuals and food handlers. The
presence of NV was detected using a reverse transcription-PCR assay. We analyzed
the risk of gastroenteritis using relative risk and its 95% confidence interval
as the measure of association, and estimated the basic reproductive number (R0).
RESULTS: The primary attack rate was 45.0%, with no significant differences
between sexes. The secondary attack rate during the camp stay was 22.7%. The
basic reproductive number for 5 days was R0=2.62. The most frequent symptoms were
abdominal pain (85.7%) and vomiting (81.9%). Epidemiological analysis showed no
association with food or drinking water. A total of 66.6% (8/12) of stool samples
tested positive for NV (genogroup II). CONCLUSION: Control measures in general,
and hand hygiene in particular, should be extended to the families once the
children return home, to prevent secondary cases in NV outbreaks.
PMID- 25117827
TI - Synthesis of novel carbazole based styryl: rational approach for photophysical
properties and TD-DFT.
AB - The synthesis and solvatochromic behavior of four novel carbazole based
fluorescent styryl dyes were explained. In chlorinated solvents such as DCM and
chloroform, these dyes show bathochromic shift in their absorption as well as
emission. The styryl dyes 6b and 6c show solid state yellow fluorescence. DFT and
TD-DFT computations were performed to study structural, molecular, electronic and
photophysical properties of these dyes. The computed absorption and emission
wavelength values are found to be in good agreement with the experimental
results. The photophysical properties of these 1-styryl carbazole dyes are also
compared with the recently reported 3-styrl carbazole dyes. The unique behavior
of dye 6d is well explained by its optimized geometry found in the excited state.
Ratio of ground to excited state dipole moment of the synthesized novel styryl
compounds were calculated by Bakhshiev and Bilot-Kawski correlations.
PMID- 25117828
TI - Synthesis, crystal structure and spectroscopic properties of a novel yttrium(III)
fluoride dimolybdate(VI): YFMo2O7.
AB - Thermal treatment of a mixture of Y2O3, YF3 and MoO3 in a 1 : 1 : 6 molar ratio
at 850 degrees C in evacuated silica ampoules yielded colorless, platelet-shaped
single crystals of YFMo2O7. SiO2 was dissolved from the ampoule wall in small
amounts, but could be removed from the crude product by treatment with
hydrofluoric acid (20%). The title compound crystallizes monoclinically in the
space group P2/c with two formula units per unit cell with the dimensions a =
4.2609(2), b = 6.5644(4), c = 11.3523(7) A, and beta = 90.511(2) degrees . Its
crystal structure contains crystallographically unique Y(3+) cations in a
pentagonal bipyramidal environment consisting of two F(-) anions in the apical
positions and five O(2-) anions in the equatorial positions. These polyhedra are
connected to {[YFO](8-)} chains along [100] by sharing common F(-) vertices. The
likewise crystallographically unique Mo(6+) cations exhibit a coordination number
of five and reside in the centers of distorted square pyramids built up of oxide
anions. These entities are fused to chains along [001] by sharing common edges
and vertices according to {[MoOOO](-)}. Taking a sixth oxygen ligand further away
from the Mo(6+) cations into account, the aforementioned chains assemble to
corrugated {[MoOOO](-)} layers perpendicular to [010] with the {[YFO](8-)} chains
situated between these sheets. Since Y(3+) represents a non-luminescent rare
earth metal(iii) cation, YFMo2O7 is a suitable host material for doping with
luminescence-active lanthanoid(iii) cations, such as Eu(3+).
PMID- 25117825
TI - Eye movements in ephedrone-induced parkinsonism.
AB - Patients with ephedrone parkinsonism (EP) show a complex, rapidly progressive,
irreversible, and levodopa non-responsive parkinsonian and dystonic syndrome due
to manganese intoxication. Eye movements may help to differentiate parkinsonian
syndromes providing insights into which brain networks are affected in the
underlying disease, but they have never been systematically studied in EP.
Horizontal and vertical eye movements were recorded in 28 EP and compared to 21
Parkinson's disease (PD) patients, and 27 age- and gender-matched healthy
subjects using standardized oculomotor tasks with infrared videooculography. EP
patients showed slow and hypometric horizontal saccades, an increased occurrence
of square wave jerks, long latencies of vertical antisaccades, a high error rate
in the horizontal antisaccade task, and made more errors than controls when pro-
and antisaccades were mixed. Based on oculomotor performance, a direct
differentiation between EP and PD was possible only by the velocity of horizontal
saccades. All remaining metrics were similar between both patient groups. EP
patients present extensive oculomotor disturbances probably due to manganese
induced damage to the basal ganglia, reflecting their role in oculomotor system.
PMID- 25117829
TI - Species variation in the enantioselective metabolism of tegafur to 5-fluorouracil
among rats, dogs and monkeys.
AB - OBJECTIVES: Tegafur (FT), a pro-drug of 5-fluorouracil (5-FU), is a racemate
consisting of two enantiomers, R and S-FT. The aim of this study was to clarify
interspecies variation in the enantioselective metabolism of FT. METHODS: Plasma
concentrations of FT enantiomers were determined in rats, dogs and monkeys
following intravenous and oral dosing of the racemate (5 mg/kg). In addition, the
enzymatic conversion of FT enantiomers to 5-FU was assayed using hepatic
preparations. KEY FINDINGS: Metabolic clearance of R-FT was higher than that of S
FT in rats and monkeys, but S-FT was the preferential substrate for dogs. An
inhibition study revealed that cytochrome P450 is primarily responsible for the
enantioselective metabolism of FT in rats and dogs. In contrast, in monkeys,
thymidine phosphorylase was a determinant of the enantioselectivity in FT
metabolism. Although oral bioavailability was not enantioselective, in-vitro and
in-vivo kinetic studies suggested that the enantioselectivity in the hepatic
intrinsic clearance of FT directly influences the body clearance in all animal
species examined. CONCLUSIONS: The interspecies variations were observed in the
enantioselective pharmacokinetics of FT, and the in-vivo enantioselectivity could
be extrapolated from the in-vitro metabolic activities.
PMID- 25117838
TI - Laparoscopic discoid anterior rectal excision with the circular stapler for
rectosigmoid endometriosis, performed by the gynecologic surgeon.
AB - STUDY OBJECTIVE: To demonstrate the technique of laparoscopic discoid anterior
rectal wall resection using a circular stapler, feasible in the case of
rectosigmoid endometriosis lesions measuring <= 3 cm. DESIGN: Case report
(Canadian Task Force classification III). SETTING: Private practice hospital in
Sao Paulo, Brazil. PATIENT: Thirty-four-year-old woman with pelvic deep
endometriosis including a 2-cm lesion in the rectosigmoid situated 11 cm
proximally to the anal border. She had chronic pelvic pain, dysmenorrhea,
dyspareunia, and constipation. She had undergone no previous surgical procedures.
INTERVENTIONS: Standard 4-puncture laparoscopy was performed, and all visible
endometriosis lesions were first removed before proceeding to rectal resection.
The avascular rectovaginal space was identified, and the rectosigmoid was
mobilized cranially, releasing the vagina and increasing the final distance of
the bowel anastomosis to the anal border. The rectosigmoid nodule was isolated in
its entire circumference and remained restricted to the anterior wall of the
bowel. It was then transfixed using a 2-0 polyglycolic suture, with the healthy
proximal and distal limits of the bowel included in the suture. A 33-cm
endoscopic circular stapler was introduced via the anus up to the distal limit of
the lesion and opened inside the bowel lumen. By pulling the edges of the suture,
the rectosigmoid nodule was introduced inside of the circular stapler. It was
fired to resect the anterior rectal wall, and the anastomosis was situated at the
anterior and lateral walls of the bowel. Integrity of the bowel was checked via
infusion of saline solution with methylene blue dye. Gynecologic surgeons
performed all of the procedures. MEASUREMENTS AND MAIN RESULTS: Bowel resection
took 20 minutes, and the entire surgical procedure lasted 120 minutes. The
patient was discharged after 48 hours. There were no intercurrent events, either
early or late postoperatively. The patient was symptom-free at 2 years of follow
up. CONCLUSION: Laparoscopic discoid excision of an anterior rectal nodule using
the circular stapler is an effective option for treating selected cases of
rectosigmoid endometriosis. The technique might be reproducible by gynecologic
surgeons after proper training.
PMID- 25117839
TI - Fertility-preserving management of a uterine arteriovenous malformation: a case
report of uterine artery embolization (UAE) followed by laparoscopic resection.
AB - Herein is presented a fertility-preserving approach in the management of a
uterine arteriovenous malformation (AVM) resistant to endovascular management.
The patient had a documented AVM and underwent 2 uterine artery embolization
procedures, with subsequent recurrence of symptoms. Doppler ultrasound
demonstrated recanalization of the AVM. Ultimately, laparoscopic resection of the
AVM was performed after laparoscopic ligation of the uterine arteries.
Postoperatively, the patient has remained asymptomatic. Laparoscopic resection of
a uterine AVM may offer a fertility-preserving alternative to hysterectomy in
patients in whom endovascular management has failed.
PMID- 25117830
TI - Pax6 is essential for the maintenance and multi-lineage differentiation of neural
stem cells, and for neuronal incorporation into the adult olfactory bulb.
AB - The paired type homeobox 6 (Pax6) transcription factor (TF) regulates multiple
aspects of neural stem cell (NSC) and neuron development in the embryonic central
nervous system. However, less is known about the role of Pax6 in the maintenance
and differentiation of adult NSCs and in adult neurogenesis. Using the +/Sey(Dey)
mouse, we have analyzed how Pax6 heterozygosis influences the self-renewal and
proliferation of adult olfactory bulb stem cells (aOBSCs). In addition, we
assessed its influence on neural differentiation, neuronal incorporation, and
cell death in the adult OB, both in vivo and in vitro. Our results indicate that
the Pax6 mutation alters Nestin(+)-cell proliferation in vivo, as well as self
renewal, proliferation, and survival of aOBSCs in vitro although a subpopulation
of +/Sey(Dey) progenitors is able to expand partially similar to wild-type
progenitors. This mutation also impairs aOBSC differentiation into neurons and
oligodendrocytes, whereas it increases cell death while preserving astrocyte
survival and differentiation. Furthermore, Pax6 heterozygosis causes a reduction
in the variety of neurochemical interneuron subtypes generated from aOBSCs in
vitro and in the incorporation of newly generated neurons into the OB in vivo.
Our findings support an important role of Pax6 in the maintenance of aOBSCs by
regulating cell death, self-renewal, and cell fate, as well as in neuronal
incorporation into the adult OB. They also suggest that deregulation of the cell
cycle machinery and TF expression in aOBSCs which are deficient in Pax6 may be at
the origin of the phenotypes observed in this adult NSC population.
PMID- 25117840
TI - Laparoscopic myomectomy: clinical outcomes and comparative evidence.
AB - Laparoscopic myomectomy is a common surgical treatment for symptomatic uterine
leiomyomas. Proponents of the laparoscopic approach to myomectomy propose that
the advantages include shorter length of hospital stay and recovery time. Others
suggest longer operative time, greater blood loss, increased risk of recurrence,
risk of uterine rupture in future pregnancies, and potential dissemination of
cells with use of morcellation. This review outlines techniques for performance
of laparoscopic myomectomy and critically appraises the available evidence for
operative data, short-term and long-term complications, and reproductive
outcomes.
PMID- 25117841
TI - Is the Allen Masters defect the most misunderstood lesion in gynecology?
PMID- 25117842
TI - The knowledge of uterine mullerian anomalies, of the pelvic female anatomy and of
the physics of ultrasounds is the basic starting point to differentiate between
septate and bicornuate uteri.
PMID- 25117843
TI - Are experiences of sexual violence related to special needs in patients with
substance use disorders? A study in opioid-dependent patients.
AB - A history of sexual violence has been related to more complex treatment needs in
patients with substance use disorders (SUD). Most of the existing studies,
however, included patients with various types of SUD, did not examine gender
differences and focused on a small range of clinical domains. Our sample
consisted of opioid-dependent outpatients treated during a three-year period in a
German metropolitan region. The analysis was based on a local case register and
included all patients for whom information on lifetime sexual violence was
available (N=3531; 68.3% males). In a case-control design, patients with a
history of sexual violence were compared to patients without these experiences
regarding a wide range of clinical and social factors indicative of potential
needs. Almost two thirds (65.6%) of the female patients and 10.9% of the males
reported experiences of sexual violence. Victims differed from non-victims across
a variety of domains, including more psychiatric symptoms and suicide attempts,
more legal problems, financial and family problems, as well as a higher use of
services. In contrast to a previous study among alcohol-dependent patients, no
gender differences became apparent. Our findings suggest that experiences of
sexual violence are an indicator for more complex needs in opioid-dependent
patients of both genders. In addition to integrated trauma-informed approaches,
an effort needs to be made to link addiction facilities to further institutions
to meet these complex needs.
PMID- 25117845
TI - A latent growth curve analysis of alcohol-use specific parenting and adolescent
alcohol use.
AB - This study investigates how changes in alcohol use-specific parenting were
associated with adolescent drinking trajectories. Three waves of data from a
longitudinal study investigating adolescent substance use were used. The
community sample (N=378) was aged 10-13 at the first wave of assessment. Our
findings show that over time, parents are less likely to discipline their
adolescents' drinking, more likely to grant their adolescent permission to drink,
and less likely to communicate the consequences of alcohol use. Moreover, these
changes are associated with escalation in adolescent alcohol use. Parental
efficacy at preventing alcohol use declined, but did not relate to changes in
adolescent drinking.
PMID- 25117844
TI - Curiosity predicts smoking experimentation independent of susceptibility in a US
national sample.
AB - PURPOSE: To improve smoking prevention efforts, better methods for identifying at
risk youth are needed. The widely used measure of susceptibility to smoking
identifies at-risk adolescents; however, it correctly identifies only about one
third of future smokers. Adding curiosity about smoking to this susceptibility
index may allow us to identify a greater proportion of future smokers while they
are still pre-teens. METHODS: We use longitudinal data from a recent national
study on parenting to prevent problem behaviors. Only oldest children between 10
and 13years of age were eligible. Participants were identified by RDD survey and
followed for 6years. All baseline never smokers with at least one follow-up
assessment were included (n=878). The association of curiosity about smoking with
future smoking behavior was assessed. Then, curiosity was added to form an
enhanced susceptibility index and sensitivity, specificity and positive
predictive value were calculated. RESULTS: Among committed never smokers at
baseline, those who were 'definitely not curious' were less likely to progress
toward smoking than both those who were 'probably not curious' (ORadj=1.89; 95%
CI=1.03-3.47) or 'probably/definitely curious' (ORadj=2.88; 95% CI=1.11-7.45).
Incorporating curiosity into the susceptibility index increased the proportion
identified as at-risk to smoke from 25.1% to 46.9%. The sensitivity (true
positives) for this enhanced susceptibility index for both experimentation and
established smoking increased from 37-40% to over 50%, although the positive
predictive value did not improve. CONCLUSION: The addition of curiosity
significantly improves the identification and classification of which adolescents
will experiment with smoking or become established smokers.
PMID- 25117846
TI - Hardcore smokers: what do we know?
AB - AIMS: The existence of smokers who are resistant to smoking cessation treatment
has long been noted in the literature. There has been ongoing debate as to
whether the proportion of these smokers is increasing as smoking prevalence rates
stagnate. Studies define hardcore smokers inconsistently and within the context
of specific illnesses, addiction, population, and/or theoretical paradigms. This
review examines the existing literature related to hardcore smokers to develop a
better understanding of what is known and not known about this group to guide
smoking cessation treatment. METHODS: PubMed MESH search and review of research
publications from 1998 to 2012 (N=61). RESULTS: Inconsistent definitions of
hardcore smoking make it difficult to estimate prevalence rates and to identify
specific characteristics of persistent smokers. Generally, persistent smokers
have higher levels of nicotine dependence, are disproportionately from lower
socioeconomic groups, start smoking at an earlier age, and are more likely to
have a psychological co-morbidity. DISCUSSION: Defining some smokers as hardcore
is limiting. Targeted and tailored interventions for smoking cessation for
persistent smoking have demonstrated effectiveness in a small number of studies.
Treatment access barriers need to be addressed to improve the reach and
effectiveness of cessation with persistent smokers. Efforts to limit early age
initiation of tobacco use are a critical element in averting persistent smoking.
PMID- 25117847
TI - Problem gambling and family violence: prevalence and patterns in treatment
seekers.
AB - The primary aim of this study was to explore the prevalence and patterns of
family violence in treatment-seeking problem gamblers. Secondary aims were to
identify the prevalence of problem gambling in a family violence victimisation
treatment sample and to explore the relationship between problem gambling and
family violence in other treatment-seeking samples. Clients from 15 Australian
treatment services were systematically screened for problem gambling using the
Brief Bio-Social Gambling Screen and for family violence using single
victimisation and perpetration items adapted from the Hurt-Insulted-Threatened
Screamed (HITS): gambling services (n=463), family violence services (n=95),
alcohol and drug services (n=47), mental health services (n=51), and financial
counselling services (n=48). The prevalence of family violence in the gambling
sample was 33.9% (11.0% victimisation only, 6.9% perpetration only, and 16.0%
both victimisation and perpetration). Female gamblers were significantly more
likely to report victimisation only (16.5% cf. 7.8%) and both victimisation and
perpetration (21.2% cf. 13.0%) than male gamblers. There were no other
demographic differences in family violence prevalence estimates. Gamblers most
commonly endorsed their parents as both the perpetrators and victims of family
violence, followed by current and former partners. The prevalence of problem
gambling in the family violence sample was 2.2%. The alcohol and drug (84.0%) and
mental health (61.6%) samples reported significantly higher rates of any family
violence than the gambling sample, while the financial counselling sample (10.6%)
reported significantly higher rates of problem gambling than the family violence
sample. The findings of this study support substantial comorbidity between
problem gambling and family violence, although this may be accounted for by a
high comorbidity with alcohol and drug use problems and other psychiatric
disorders. They highlight the need for routine screening, assessment and
management of problem gambling and family violence in a range of services.
PMID- 25117848
TI - Environmental tobacco smoke exposure among smokers and non-smokers receiving
outpatient substance abuse treatment.
AB - INTRODUCTION: Environmental Tobacco Smoke (ETS) has been linked to numerous
health problems. While research has demonstrated high prevalence of tobacco use
among individuals receiving treatment for substance use disorders (SUDs), no
studies have examined ETS among individuals receiving treatment for SUDs, paying
specific attention to non-smokers who may be at risk for high exposure to ETS.
METHODS: Participants (N=261) enrolled in outpatient substance abuse treatment
completed a survey, in which 14 items were used to quantify ETS exposure and
smoking policies across several environments. RESULTS: Among smokers, 85%
reported that their significant others also smoked as compared to 15% among non
smokers (chi(2)=6.624, p<.05). A logistic regression examined the characteristics
that predicted smoking in the home. The overall model was significant,
(chi(2)=36.046, p<.0005) with variables that independently predicted smoking in
the home included having less than a high school diploma, being female, and
living with a smoker. Income, age, and living with children were not found to be
significant. Overall, 42% white collar workers 26% of service workers and 30% of
blue collar workers reported no exposure to ETS. Sixty-seven percent of smokers
strongly agreed or agreed that the hazards of secondhand smoke have been clearly
demonstrated versus 58% of non-smokers. CONCLUSIONS: Smokers and non-smokers
enrolled in outpatient substance abuse treatment are frequently exposed to ETS at
home, work, and in social settings. The dangers of ETS should be addressed among
this population through education, smoke-free policies, and cessation resources,
with help from their treatment facility.
PMID- 25117849
TI - Negative affect is associated with alcohol, but not cigarette use in heavy
drinking smokers.
AB - Co-use of alcohol and cigarettes is highly prevalent, and heavy drinking smokers
represent a large and difficult-to-treat subgroup of smokers. Negative affect,
including anxiety and depressive symptomatology, has been associated with both
cigarette and alcohol use independently, but less is known about the role of
negative affect in heavy drinking smokers. Furthermore, while some studies have
shown negative affect to precede substance use, a precise biobehavioral mechanism
has not been established. The aims of the present study were twofold. First, to
test whether negative affect is associated with alcohol and cigarette use in a
large community sample of heavy drinking smokers (n=461). And second, to examine
craving as a plausible statistical mediator of the association between negative
affect and alcohol and/or cigarette use. Hypothesis testing was conducted using a
structural equation modeling approach with cross-sectional data. Analysis
revealed a significant main effect of negative affect on alcohol use (beta=0.210,
p<0.05), but not cigarette use (beta=0.131, p>0.10) in this sample. Mediational
analysis revealed that alcohol craving was a full statistical mediator of this
association (p<0.05), such that there was no direct association between negative
affect and alcohol use after accounting for alcohol craving. These results are
consistent with a negative reinforcement and relief craving models of alcohol use
insofar as the experience of negative affect was associated with increased
alcohol use, and the relationship was statistically mediated by alcohol craving,
presumably to alleviate negative affect. Further longitudinal or experimental
studies are warranted to enhance the causal inferences of this mediated effect.
PMID- 25117850
TI - Differences between abstinent and non-abstinent individuals in recovery from
alcohol use disorders.
AB - OBJECTIVE: Non-abstinent goals can improve quality of life (QOL) among
individuals with alcohol use disorders (AUDs). However, prior studies have
defined "recovery" based on DSM criteria, and thus may have excluded individuals
using non-abstinent techniques that do not involve reduced drinking. Furthermore,
no prior study has considered length of time in recovery when comparing QOL
between abstinent and non-abstinent individuals. The current aims are to identify
correlates of non-abstinent recovery and examine differences in QOL between
abstainers and non-abstainers accounting for length of time in recovery. SAMPLE:
A large (N=5380) national sample of individuals who self-describe as "in
recovery" from alcohol problems recruited in the context of the What Is Recovery?
(WIR) study. METHOD: Multivariate stepwise regressions estimating the probability
of non-abstinent recovery and average quality of life. RESULTS: Younger age
(OR=0.72), no prior treatment (OR=0.63) or AA (OR=0.32), fewer dependence
symptoms (OR=0.17) and less time in recovery all significantly (P<0.05) related
to non-abstinent recovery. Abstainers reported significantly (P<0.05) higher QOL
than non-abstainers (B=0.39 for abstinence vs. non-abstinence), and abstinence
was one of the strongest correlates of QOL, even beyond sociodemographic
variables like education. CONCLUSIONS: Non-abstainers are younger with less time
in recovery and less problem severity but worse QOL than abstainers. Clinically,
individuals considering non-abstinent goals should be aware that abstinence may
be best for optimal QOL in the long run. Furthermore, time in recovery should be
accounted for when examining correlates of recovery.
PMID- 25117851
TI - Methadone maintenance treatment may improve completion rates and delay opioid
relapse for opioid dependent individuals under community corrections supervision.
AB - AIMS: Several studies have demonstrated the importance of agonist therapies such
as methadone and buprenorphine for preventing relapse for individuals being
released from jail or prison to the community. No studies have examined the
impact of methadone for increasing the completion of community supervision
requirements and preventing opioid relapse for individuals under community
corrections supervision. This observational study compared the community
corrections completion rate and opioid relapse rate of individuals receiving
methadone maintenance therapy (MMT) to individuals who did not. METHODS: Of the
2931 individuals enrolled under criminal justice supervision in the community,
Treatment Accountability for Safer Communities (TASC), and who met criteria for
opioid dependence, 329 (11%) individuals reported receiving MMT in the community.
RESULTS: The majority of participants were White (79.8%) and male (63.5%), with a
mean age of 31.33years (SD=9.18), and were under supervision for 10.4months
(SD=9.1). MMT participants were less likely to fail out of supervision compared
to individuals not in MMT (39.0% vs. 52.9%, p<0.001), and had a lower rate of
relapse (32.9%) and longer time to relapse (average days=89.7, SD=158.9) compared
to the relapse rate (55.9%) and time to relapse (average days=60.5, SD=117.9) of
those not on MMT. CONCLUSIONS: While the observational nature of this study
prevents causal inferences, these results suggest that utilization of MMT in
community corrections may increase the likelihood of completing supervision
requirements and delay time to opioid relapse. Providing agonist therapies to
opioid dependent individuals under supervision appears to be a critical strategy
in this important population.
PMID- 25117853
TI - Population dose-response analysis of daily seizure count following vigabatrin
therapy in adult and pediatric patients with refractory complex partial seizures.
AB - Vigabatrin is an irreversible inhibitor of gamma-aminobutyric acid transaminase
(GABA-T) and is used as an adjunctive therapy for adult patients with refractory
complex partial seizures (rCPS). The purpose of this investigation was to
describe the relationship between vigabatrin dosage and daily seizure rate for
adults and children with rCPS and identify relevant covariates that might impact
seizure frequency. This population dose-response analysis used seizure-count data
from three pediatric and two adult randomized controlled studies of rCPS
patients. A negative binomial distribution model adequately described daily
seizure data. Mean seizure rate decreased with time after first dose and was
described using an asymptotic model. Vigabatrin drug effects were best
characterized by a quadratic model using normalized dosage as the exposure
metric. Normalized dosage was an estimated parameter that allowed for
individualized changes in vigabatrin exposure based on body weight. Baseline
seizure rate increased with decreasing age, but age had no impact on vigabatrin
drug effects after dosage was normalized for body weight differences. Posterior
predictive checks indicated the final model was capable of simulating data
consistent with observed daily seizure counts. Total normalized vigabatrin
dosages of 1, 3, and 6 g/day were predicted to reduce seizure rates 23.2%, 45.6%,
and 48.5%, respectively.
PMID- 25117854
TI - Combined electrical and global markers of dyssynchrony predict clinical response
to cardiac resynchronization therapy.
AB - AIM: To assess potential additional value of global left ventricular (LV)
dyssynchrony markers in predicting cardiac resynchronization therapy (CRT)
response in heart failure (HF) patients. METHODS: We included 103 HF patients
(mean age 67 +/- 12 years, 83% male) who fulfilled the guidelines criteria for
CRT treatment. All patients had undergone full clinical assessment, NT-proBNP and
echocardiographic examination. Global LV dyssynchrony was assessed using total
isovolumic time (t-IVT) and Tei index. On the basis of reduction in the NYHA
class after CRT, patients were divided into responders and non-responders.
RESULTS: Prolonged t-IVT [0.878 (range, 0.802-0.962), p = 0.005], long QRS
duration [0.978 (range, 0.960-0.996), p = 0.02] and high tricuspid regurgitation
pressure drop [1.047 (range, 1.001-1.096), p = 0.046] independently predicted
response to CRT. A t-IVT >= 11.6 s/min was 67% sensitive and 62% specific (AUC
0.69, p = 0.001) in predicting CRT response. Respective values for a QRS >= 151
ms were 66% and 62% (AUC 0.65, p = 0.01). Combining the two variables had higher
specificity (88%) in predicting CRT response. In atrial fibrillation (AF)
patients, only prolonged t-IVT [0.690 (range, 0.509-0.937), p = 0.03]
independently predicted CRT response. CONCLUSION: Combining prolonged t-IVT and
the conventionally used broad QRS duration has a significantly higher specificity
in identifying patients likely to respond to CRT. Moreover, in AF patients, only
prolonged t-IVT independently predicted CRT response.
PMID- 25117852
TI - At-Risk/Problematic Shopping and Gambling in Adolescence.
AB - Elevated levels of both pathological gambling (PG) and problem shopping (PS) have
been reported among adolescents, and each is associated with a range of other
negative health/functioning measures. However, relationships between PS and PG,
particularly during adolescence, are not well understood. In this study, we
explored the relationship between different levels of problem-gambling severity
and health/functioning characteristics, gambling-related social experiences,
gambling behaviors and motivations among adolescents with and without at
risk/problematic shopping (ARPS). Survey data from Connecticut high school
students (n = 2,100) were analyzed using bivariate analyses and logistic
regression modeling. Although at-risk/problematic gambling (ARPG) was not
increased among adolescents with ARPS, adolescents with ARPG (vs non-gamblers)
were more likely to report having experienced a growing tension or anxiety that
could only be relieved by shopping and missing other obligations due to shopping.
In comparison to the non-ARPS group, a smaller proportion of respondents in the
ARPS group reported paid part-time employment, whereas a greater proportion of
respondents reported excessive gambling by peers and feeling concerned over the
gambling of a close family member. In general, similar associations between
problem-gambling severity and measures of health/functioning and gambling-related
behaviors and motivations were observed across ARPS and non-ARPS adolescents.
However, associations were weaker among ARPS adolescents for several variables:
engagement in extracurricular activities, alcohol and caffeine use and gambling
for financial reasons. These findings suggest a complex relationship between
problem-gambling severity and ARPS. They highlight the importance of considering
co-occurring risk behaviors such as ARPS when treating adolescents with at
risk/problem gambling.
PMID- 25117855
TI - Examination of spatiotemporal gait parameters during the 6-min walk in
individuals with multiple sclerosis.
AB - This investigation examined spatiotemporal parameters of gait during the 6-min
walk (6MW) in individuals with multiple sclerosis (MS) and in healthy controls.
Eighteen individuals with MS [divided into those who were independently
ambulatory (n=10) and those who were ambulatory with assistance (n=8)] and 10
healthy controls performed a 6MW while recording spatiotemporal gait parameters
using a pressure-sensitive walkway. Parameters recorded were walking velocity,
cadence, step length and width, step time, percent of the gait cycle in double
support, and variability of step length and width, step time, and double support.
The ambulatory with assistance MS group had a significantly greater reduction in
walking velocity (P=0.000) over the course of the 6MW, which coincided with a
significantly greater increase in step time and double support (P=0.029) than in
the other groups. Only the ambulatory with assistance MS group showed an increase
in step-time variability and double-support variability during the 6MW
(P's<0.05). The novel results indicate that the reduction in velocity over
prolonged walking occurs through a greater change in the temporal parameters of
gait in persons with MS who require assistance while walking. In addition, the
increase in gait variability in the individuals with MS who require assistance
while walking indicates that the control over walking further deteriorates over
the course of the 6MW.
PMID- 25117856
TI - Adherence to evidence based care practices for childbirth before and after a
quality improvement intervention in health facilities of Rajasthan, India.
AB - BACKGROUND: After the launch of Janani Suraksha Yojana, a conditional cash
transfer scheme in India, the proportion of women giving birth in institutions
has rapidly increased. However, there are important gaps in quality of childbirth
services during institutional deliveries. The aim of this intervention was to
improve the quality of childbirth services in selected high caseload public
health facilities of 10 districts of Rajasthan. This intervention titled
"Parijaat" was designed by Action Research & Training for Health, in partnership
with the state government and United Nations Population Fund. METHODS: The
intervention was carried out in 44 public health facilities in 10 districts of
Rajasthan, India. These included district hospitals (9), community health centres
(32) and primary health centres (3). The main intervention was orientation
training of doctors and program managers and regular visits to facilities
involving assessment, feedback, training and action. The adherence to evidence
based practices before, during and after this intervention were measured using
structured checklists and scoring sheets. Main outcome measures included changes
in practices during labour, delivery or immediate postpartum period. RESULTS: Use
of several unnecessary or harmful practices reduced significantly. Most
importantly, proportion of facilities using routine augmentation of labour
reduced (p = 0), episiotomy for primigravidas (p = 0.0003), fundal pressure (p =
0.0003), and routine suction of newborns (0 = 0.0005). Among the beneficial
practices, use of oxytocin after delivery increased (p = 0.0001) and the practice
of listening foetal heart sounds during labour (p = 0.0001). Some practices did
not show any improvements, such as dorsal position for delivery, use of
partograph, and hand-washing. CONCLUSIONS: An intervention based on repeated
facility visits combined with actions at the level of decision makers can lead to
substantial improvements in quality of childbirth practices at health facilities.
PMID- 25117858
TI - [Reconciling activities of working women providing care and the influence of
structural and cultural factors].
AB - BACKGROUND: Today, an increasing proportion of society has to reconcile eldercare
and work. This task poses challenges for them, which they meet through an
adjustment of their everyday living arrangements. These coping strategies have
been so far scarcely noted within research on the reconciliation of elder care
and employment. Knowledge about the active dealing with this parallel involvement
in both spheres of life is of vital importance when wanting to derive precisely
tailored support measures for employed care givers. MATERIALS AND METHODS: A goal
of this article is to deliver insight on reconciling activities of employed women
who provide care, while it tries to specify respective factors which determine
those actions. Moreover, an ideal typology is presented, which systematizes these
associations. RESULTS: With this ideal typology, conceptual instruments have been
developed which illustrate the complex reality of the reconciliation actions and
the dependence on various coping resources. In gerontological practice, these
findings may provide support to design an intervention strategy tailored to the
individual situation that addresses the everyday level of action and strengthens
the performance of those affected.
PMID- 25117857
TI - [Sleep and sleep disorders in the elderly: Part 1: epidemiology and diagnostics].
AB - Restorative sleep is an important factor for well-being, performance and quality
of life. The basic diagnostic procedure of a sleep disorder is to take a
comprehensive sleep history. Sleep disorders can and must be distinguished from
the physiological changes of sleep in the elderly. Insomnia (difficulty in
sleeping), daytime sleepiness (hypersomnia), sleep-related breathing disorders
(SRBD) and movement disorders during sleep are also common in the elderly. They
must be detected because they are treatable and can dominate the clinical picture
of geriatric syndromes. Nursing home residents and dementia patients are in
particular need of attention as their sleep is often adversely affected by the
living environment and the daily institutional routine.
PMID- 25117859
TI - The emerging trend of work beyond retirement age in Germany. Increasing social
inequality?
AB - BACKGROUND: Population ageing, demographic change and the financial crisis has
put the financial sustainability of the German pension system at risk. In
reaction to these challenges, Germany recently abandoned generous early
retirement policies and moved towards policies encouraging higher employment
among the elderly. OBJECTIVES: In this article we evaluate how these labour
market and pension policies affected the retirement decisions of older workers in
Germany over the last three decades. Complementing previous research on early
retirement, we focus in particular on those working past the mandatory retirement
age of 65 years and examine whether the composition of this group of
postretirement-age workers has changed over time. DATA AND METHODS: We analyse
pooled cross-sectional data from three rounds of the German Ageing Survey which
allow us to cover the last three decades from 1980 to 2008. Estimating
multinomial logit models we distinguish explanatory factors on the individual,
organizational and institutional level that frame the decision to leave the
labour market before the age of 65, to stop working at 65 or to work past 65.
RESULTS: Over the last three decades, the share of German workers leaving the
labour market after the mandatory retirement age of 65 has increased markedly.
This trend towards working longer has changed particularly among the low educated
workforce which in previous decades traditionally has exhibited a tendency to
retire early. In contrast to high-skilled workers, the decision to work longer
among low-educated workers is mainly driven by financial need (and is usually not
in line with their desire or their ability to work for longer). CONCLUSION: Our
findings suggest an increase in social inequality in retirement decisions as a
result of the policy shift towards activation. We conclude by arguing for a more
fine-grained understanding of the reasons why people work longer. Such research
would provide valuable insights into how to design future labour market and
pension reforms preventing a rise in social inequalities.
PMID- 25117860
TI - [Aged skin and skin care].
AB - BACKGROUND: Aged skin is the sum of chronological und UV-induced aging. Light
exposed skin is unattractive, with irregular pigmentation, roughness und
scaliness. The skin is often dry and itches. METHODS: The present paper provides
an overview of diseases of aging skin and describes how to prevent or reduce
disease by prophylactic and therapeutic skin care. RESULTS: Aged skin can develop
into several skin diseases, e.g., different types of eczema and skin cancer. In
the body folds we often find an irritant contact eczema caused by friction from
skin to skin, sweating, and urinary and fecal incontinence. In the bedridden, bed
sores can also develop. Furthermore, there is a delay in wound healing owing to
old age. Use of adequate creams and ointments is very helpful in preventing and
improving most skin diseases of mature skin. However, the knowledge of aged
people and healthcare professionals about the importance of skin care is low.
Older people are often unable to care for their skin because they are lacking the
physical and mental ability. CONCLUSION: Healthcare professionals are not
sufficiently trained about the value of proper skin care. Adequate studies on the
role of skin care and selection of the correct preparation in various aged
related diseases are lacking.
PMID- 25117861
TI - Dysfunctional sexual beliefs: a comparative study of heterosexual men and women,
gay men, and lesbian women with and without sexual problems.
AB - INTRODUCTION: Conservative and dysfunctional sexual beliefs are commonly
associated with sexual problems among heterosexual men and women. However, little
is known about the role of sexual beliefs in sexual problems in gay men and
lesbians. AIM: The present study aimed at analyzing the role of sexual beliefs in
sexual dysfunction in a sample of heterosexual and homosexual men and women. MAIN
OUTCOME MEASURES: Participants answered questions about self-perceived sexual
problems and completed the Sexual Dysfunctional Beliefs Questionnaire. METHODS:
Two hundred twelve men (106 gay) and 192 women (96 lesbian) completed a Web
survey. RESULTS: Findings indicated that men with sexual dysfunction (regardless
of sexual orientation) reported significantly more conservative beliefs and more
erroneous beliefs related to partner's sexual satisfaction compared with sexually
healthy men. Also, gay men with sexual dysfunction (but not heterosexual men)
scored higher on belief in sex as an abuse of men's power compared with healthy
controls. In addition, heterosexual men scored higher on "macho" beliefs, beliefs
regarding partner's sexual satisfaction, and partner's power, compared with gay
men. For women, a main effect was found for sexual orientation, with lesbian
women scoring higher on sexual desire as a sin, age-related beliefs, and
affection primacy and lower on beliefs related to motherhood primacy.
CONCLUSIONS: Overall, findings suggest that dysfunctional sexual beliefs may play
a role as vulnerability factors for sexual dysfunction regardless of sexual
orientation, particularly in men.
PMID- 25117863
TI - Chronic renal disease and risk of cardiovascular morbidity-mortality.
AB - The pathogenesis of cardiovascular disease in CKD differs subtly from that of non
CKD patients. As renal function declines, the role and impact of treating
classical risk factors may change and diminish. However, hypertension,
hypercholesterolaemia and smoking cessation management should be optimized and
may require multiple agents and approaches, particularly as CKD advances.
Hypertension treatment would appear to be one management area in which
performance is less than ideal. Moreover there are mechanisms and risk factors
that are specific to CKD, capable of triggering a vascular pathology and that
justify the surplus of CV morbidity in CKD patients and that require we consider
CKD as a CV risk factor per se. In the initial stages of CKD it would be
advisable to implement all the preventative measures to stem the onset of CV
disease, whereas in the more advanced stages a multifactorial approach is likely
to be necessary, as we have learned from the STENO-study within the diabetes.
PMID- 25117862
TI - The dUTPase-related gene of bovine immunodeficiency virus is critical for viral
replication, despite the lack of dUTPase activity of the encoded protein.
AB - BACKGROUND: Deoxyuridine 5'-triphosphate nucleotide-hydrolases (dUTPases) are
essential for maintaining low intra-cellular dUTP/dTTP ratios. Therefore, many
viruses encode this enzyme to prevent dUTP incorporation into their genomes
instead of dTTP. Among the lentiviruses, the non-primate viruses express
dUTPases. In bovine immunodeficiency virus (BIV), the putative dUTPase protein is
only 74 residues-long, compared to ~130 residues in other lentiviruses. RESULTS:
In this study, the recombinant BIV dUTPase, as well as infectious wild-type (WT)
BIV virions, were shown to lack any detectable dUTPase activity. Controls of
recombinant dUTPase from equine infectious anemia virus (EIAV) or of EIAV virions
showed substantial dUTPase activities. To assess the importance of the dUTPase to
BIV replication, we have generated virions of WT BIV or BIV with mutations in the
dUTPase gene. The two mutant viral dUTPases were the double mutant D48E/N57S (in
the putative enzyme active site and its vicinity) and a deletion of 36 residues.
In dividing Cf2Th cells and under conditions where the WT virus was infectious
and generated progeny virions, both mutant viruses were defective, as no progeny
viruses were generated. Analyses of the integrated viral cDNA showed that cells
infected with the mutant virions carry in their genomic DNA levels of integrated
BIV DNA that are comparable to those in WT BIV-infected cells. CONCLUSIONS: The
herby presented results show that the two BIV mutants with the modified dUTPase
gene could infect cells, as viral cDNA was synthesized and integrated into the
host cell DNA. However, no virions were generated by cells infected by these
mutants. The most likely explanation is that either the integrated cDNA of the
mutants is defective (due to potential multiple mutations, introduced during
reverse-transcription) or that the original dUTPase mutations have led to severe
blocks in viral replication at steps post integration. These results emphasize
the importance of the dUTPase-related sequence to BIV replication, despite the
lack of any detectable catalytic activity.
PMID- 25117864
TI - Uliginosin B, a natural phloroglucinol derivative, presents a multimediated
antinociceptive effect in mice.
AB - OBJECTIVE: Investigate the involvement of monoaminergic and glutamatergic systems
on the antinociceptive and ataxic effects of uliginosin B, which we have already
demonstrated to be a promising molecular scaffold to develop new analgesic drugs.
METHODS: Uliginosin B was obtained from hexane extract of aerial parts of
Hypericum polyanthemum by chromatographic methods. Uliginosin B antinociceptive
and motor coordination effects were evaluated in mice by using hot-plate (15 and
90 mg/kg, i.p.) and rotarod (90 mg/kg, i.p.) tests, respectively. The mechanism
of action was investigated through pretreatments with prazosin 1 mg/kg
intraperitoneal (alpha1 receptor antagonist), yohimbine 5 mg/kg intraperitoneal
(alpha2 receptor antagonist), pCPA 300 mg/kg intraperitoneal (serotonin synthesis
inhibitor) and MK-801 0.25 mg/kg intraperitoneal (N-methyl-D-aspartic acid
receptor antagonist). KEY FINDINGS: The antinociceptive effect of uliginosin B
(15 and 90 mg/kg, i.p.) was reduced significantly by pCPA and MK-801. Prazosin
and yohimbine improved the antinociceptive effect of the highest dose (90 mg/kg,
i.p.) of uliginosin B only. The ataxic effect of uliginosin B (90 mg/kg, i.p.)
was completely prevented by pretreatment with pCPA or MK-801, but it was
unaffected by pretreatment with prazosin or yohimbine. CONCLUSION: These data
confirm the contribution of monoaminergic neurotransmission as well as provide
the first evidence of glutamatergic neurotransmission contribution to the
uliginosin B effects.
PMID- 25117865
TI - Airway complications in traumatic lower cervical spinal cord injury: A
retrospective study.
AB - OBJECTIVE: To investigate risk factors for pneumonia in patients with traumatic
lower cervical spinal cord injury. DESIGN: Observational study, retrospective
study. SETTING: Spinal cord unit in a maximum care hospital. METHODS: Thirty
seven patients with acute isolated traumatic spinal cord injury at levels C4-C8
and complete motor function injury (AIS A, B) treated from 2004 to 2010 met the
criteria for inclusion in our retrospective analysis. The following parameters
were considered: ventilation-specific parameters, re-intubation, creation of a
tracheostomy, pneumonia, antibiotic treatment, and length of intensive care unit
(ICU) stay and total hospitalization. RESULTS: Among the patients, 81% had
primary invasive ventilation. In 78% of cases a tracheostomy was created; 3% of
these cases were discharged with invasive ventilation and 28% with a tracheostomy
without ventilation. Pneumonia according to Centers for Disease Control criteria
occurred in 51% of cases within 21+/-32 days of injury, and in 3% at a later
date. The number of pre-existing conditions was significantly associated with
pneumonia. Length of ICU stay was 25+/-34 days, and average total hospital
duration was 230+/-144 days. Significant factors affecting the duration of
ventilation were the number of pre-existing conditions and tetraplegia-specific
complications. CONCLUSIONS: Our results confirm that patients with traumatic
lower cervical spinal cord injuries defined by lesion level and AIS constitute a
homogeneous group. This group is characterized by a high rate of pneumonia during
the first 4 weeks after injury. The number of pre-existing general conditions and
spinal injury-specific comorbidities are the only risk factors identified for the
development of pneumonia and/or duration of ventilation.
PMID- 25117871
TI - Effects of the racket polar moment of inertia on dominant upper limb joint
moments during tennis serve.
AB - This study examined the effect of the polar moment of inertia of a tennis racket
on upper limb loading in the serve. Eight amateur competition tennis players
performed two sets of 10 serves using two rackets identical in mass, position of
center of mass and moments of inertia other than the polar moment of inertia
(0.00152 vs 0.00197 kg.m2). An eight-camera motion analysis system collected the
3D trajectories of 16 markers, located on the thorax, upper limbs and racket,
from which shoulder, elbow and wrist net joint moments and powers were computed
using inverse dynamics. During the cocking phase, increased racket polar moment
of inertia was associated with significant increases in the peak shoulder
extension and abduction moments, as well the peak elbow extension, valgus and
supination moments. During the forward swing phase, peak wrist extension and
radial deviation moments significantly increased with polar moment of inertia.
During the follow-through phase, the peak shoulder adduction, elbow pronation and
wrist external rotation moments displayed a significant inverse relationship with
polar moment of inertia. During the forward swing, the magnitudes of negative
joint power at the elbow and wrist were significantly larger when players served
using the racket with a higher polar moment of inertia. Although a larger polar
of inertia allows players to better tolerate off-center impacts, it also appears
to place additional loads on the upper extremity when serving and may therefore
increase injury risk in tennis players.
PMID- 25117873
TI - Cross-education strength and activation after eccentric exercise.
AB - CONTEXT: After injury, eccentric exercise of the injured limb is often
contraindicated. Cross-education training, whereby the uninvolved limb is
exercised, is an alternative that may improve quadriceps muscle strength and
activation in the unexercised limb. OBJECTIVE: To determine the effect of
eccentric exercise on quadriceps strength and activation gains in the unexercised
limb. PATIENTS OR OTHER PARTICIPANTS: Eighteen healthy individuals were randomly
assigned to an eccentric training group or a control group. INTERVENTION(S):
Quadriceps strength and activation measures were collected at preintervention,
midintervention, and postintervention. Eccentric training participants exercised
their dominant limb with a dynamometer in eccentric mode at 60 degrees /s, 3
times per week for 8 weeks. MAIN OUTCOME MEASURE(S): Quadriceps strength was
quantified at 30 degrees and 60 degrees /s in concentric and eccentric modes.
Quadriceps activation was assessed using the burst superimposition technique and
quantified via the central activation ratio. A 2 * 3 repeated-measures analysis
of variance was used to detect the effects of group and testing session on
quadriceps strength and activation. Where appropriate, post hoc Bonferroni
multiple-comparisons procedures were used. RESULTS: We found greater eccentric
strength in the unexercised limbs of eccentric training participants between
preintervention and midintervention and between preintervention and
postintervention (preintervention to midintervention: 30 degrees /s P = .05;
preintervention to postintervention: 30 degrees /s P = .02, 60 degrees /s P =
.02). No differences were noted in concentric strength (P > .05). An overall
trend toward greater quadriceps activation in the unexercised knee was detected
between preintervention and postintervention (P = .063), with the eccentric
training group demonstrating a strong effect (Cohen d = 0.83). Control strength
did not change (P > .05). CONCLUSIONS: Exercising with eccentric actions resulted
in mode-specific and velocity-specific gains in quadriceps strength in the
unexercised limb. A trend toward greater quadriceps activation in the unexercised
knee was noted, suggesting that strength gains may have occurred because of
enhanced neural activity. This type of therapy may be a useful addition to
rehabilitation programs designed to improve quadriceps strength.
PMID- 25117872
TI - What's behind a sand fly bite? The profound effect of sand fly saliva on host
hemostasis, inflammation and immunity.
AB - Sand flies are blood-feeding insects and vectors of the Leishmania parasite. For
many years, saliva of these insects has represented a gold mine for the discovery
of molecules with anti-hemostatic and immuno-modulatory activities. Furthermore,
proteins in sand fly saliva have been shown to be a potential vaccine against
leishmaniasis and also markers of vector exposure. A bottleneck to progress in
these areas of research has been the identification of molecules responsible for
the observed activities and properties of saliva. Over the past decade, rapid
advances in transcriptomics and proteomics resulted in the completion of a number
of sialomes (salivary gland transcriptomes) and the expression of several
recombinant salivary proteins from different species of sand fly vectors. This
review will provide readers with a comprehensive update of recent advances in the
characterization of these salivary molecules and their biological activities and
offer insights pertaining to their protective effect against leishmaniasis and
their potential as markers of vector exposure.
PMID- 25117874
TI - Holistic life-span health outcomes among elite intercollegiate student-athletes.
AB - CONTEXT: Competitive sports are recognized as having unique health benefits and
risks, and the effect of sports on life-span health among elite athletes has
received increasing attention. However, supporting scientific data are sparse and
do not represent modern athletes. OBJECTIVE: To assess holistic life-span health
and health-related quality-of-life (HRQL) among current and former National
Collegiate Athletic Association student-athletes (SAs). DESIGN: Cross-sectional
study. SETTING: A large Division I university. PATIENTS OR OTHER PARTICIPANTS:
Population-based sample of 496 university students and alumni (age 17-84 years),
including SAs and an age-matched and sex-matched nonathlete (NA) control group.
MAIN OUTCOME MEASURE(S): Participants completed anonymous, self-report
questionnaires. We measured the Short-Form 12 (SF-12) physical and mental
component HRQL scores and cumulative lifetime experience and relative risk of
treatment for joint, cardiopulmonary, and psychosocial health concerns. RESULTS:
Older alumni (age 43+ years) SAs reported greater joint health concerns than NAs
(larger joint summary scores; P = .04; Cohen d = 0.69; probability of clinically
important difference [pCID] = 77%; treatment odds ratio [OR] = 14.0, 95%
confidence interval [CI] = 1.6, 126). Joint health for current and younger alumni
SAs was similar to that for NAs. Older alumni reported greater cardiopulmonary
health concerns than younger alumni (summary score P < .001; d = 1.05; pCID =
85%; OR = 5.8, 95% CI = 2.0, 16) and current students (P < .001; d = 2.25; pCID
>99.5%; OR = 7.1, 95% CI = 3.3, 15), but the risk was similar for SAs and NAs.
Current SAs demonstrated evidence of better psychosocial health (summary score P
= .006; d = -0.52; pCID = 40%) and mental component HRQL (P = .008; d = 0.50;
pCID = 48%) versus NAs but similar psychosocial treatment odds (OR = 0.87, 95% CI
= 0.39, 1.9). Psychosocial health and mental component HRQL were similar between
alumni SAs and NAs. No differences were observed between SAs and NAs in physical
component HRQL. CONCLUSIONS: The SAs demonstrated significant, clinically
meaningful evidence of greater joint health concerns later in life, comparable
cardiopulmonary health, and differences in life-span psychosocial health and HRQL
profiles compared with NAs. These data provide timely evidence regarding a
compelling public issue and highlight the need for further study of life-span
health among modern athletes.
PMID- 25117876
TI - Effect of electrohydraulic shockwave treatment on tenderness, muscle cathepsin
and peptidase activities and microstructure of beef loin steaks from Holstein
young bulls.
AB - Hydrodynamic pressure processing (HDP) or shockwave treatment improved tenderness
(18% reduction in Warner-Bratzler shear force (WBSF) of beef loin steaks.
Endogenous muscle proteolyic activities (cathepsins and peptidases) and protein
fragmentation of sarcoplasmic and myofibrillar proteins detected by sodium
dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were not influenced
by HDP. However, microstructure changes were clearly detected using confocal
laser scanning microscopy (CLSM) and scanning electron microscopy (SEM).
Specifically a disruption of the structure at the muscle fiber bundles and an
increased endomysium space were observed. The present paper supports the evidence
of physical disruption of the muscle fibers as a cause behind the tenderness
improvement. The paper discusses the possible mechanisms responsible for the meat
tenderisation induced by HDP treatment.
PMID- 25117875
TI - Risk of Lower Extremity Injury in a Military Cadet Population After a Supervised
Injury-Prevention Program.
AB - CONTEXT: Specific movement patterns have been identified as possible risk
factors for noncontact lower extremity injuries. The Dynamic Integrated Movement
Enhancement (DIME) was developed to modify these movement patterns to decrease
injury risk. OBJECTIVE: To determine if the DIME is effective for preventing
lower extremity injuries in US Military Academy (USMA) cadets. DESIGN: Cluster
randomized controlled trial. SETTING: Cadet Basic Training at USMA. PATIENTS OR
OTHER PARTICIPANTS: Participants were 1313 cadets (1070 men, 243 women).
INTERVENTION(S): Participants were cluster randomized to 3 groups. The active
warm-up (AWU) group performed standard Army warm-up exercises. The DIME groups
were assigned to a DIME cadre-supervised (DCS) group or a DIME expert-supervised
(DES) group; the former consisted of cadet supervision and the latter combined
cadet and health professional supervision. Groups performed exercises 3 times
weekly for 6 weeks. MAIN OUTCOME MEASURE(S): Cumulative risk of lower extremity
injury was the primary outcome. We gathered data during Cadet Basic Training and
for 9 months during the subsequent academic year. Risk ratios and 95% confidence
intervals (CIs) were calculated to compare groups. RESULTS: No differences were
seen between the AWU and the combined DIME (DCS and DES) groups during Cadet
Basic Training or the academic year. During the academic year, lower extremity
injury risk in the DES group decreased 41% (relative risk [RR] = 0.59; 95% CI =
0.38, 0.93; P = .02) compared with the DCS group; a nonsignificant 25% (RR =
0.75; 95% CI = 0.49, 1.14; P = .18) decrease occurred in the DES group compared
with the AWU group. Finally, there was a nonsignificant 27% (RR = 1.27; 95% CI =
0.90, 1.78; P = .17) increase in injury risk during the academic year in the DCS
group compared with the AWU group. CONCLUSIONS: We observed no differences in
lower extremity injury risk between the AWU and combined DIME groups. However,
the magnitude and direction of the risk ratios in the DES group compared with the
AWU group, although not statistically significant, indicate that professional
supervision may be a factor in the success of injury-prevention programs.
PMID- 25117877
TI - Is health a right for all? An umbrella review of the barriers to health care
access faced by migrants.
AB - OBJECTIVE: To synthesise the scientific evidence concerning barriers to health
care access faced by migrants. We sought to critically analyse this evidence with
a view to guiding policies. DESIGN: A systematic review methodology was used to
identify systematic and scoping reviews which quantitatively or qualitatively
analysed data from primary studies. The main variables analysed were structural
and contextual barriers (health system organisation) as well as individual
(patients and providers). The quality of evidence from the systematic reviews was
critically appraised. From 2674 reviews, 79 were retained for further scrutiny,
and finally 9 met the inclusion criteria. RESULTS: The structural barriers
identified were the lack of health insurance and the high cost of drugs (non
universal health system) and organisational aspects of health system (social
insurance system and national health system). The individual barriers were
linguistic and cultural. None of the reviews provided a quality appraisal of the
studies. CONCLUSIONS: Barriers to health care for migrants range from entitlement
in non-universal health systems to accessibility in universal ones, and
determinants of access to the respective health services should be analysed
within the corresponding national context. Generate social and institutional
changes that eliminate barriers to access to health services is essential to
ensure health for all.
PMID- 25117878
TI - Factors characterizing access and latency to first pharmacological treatment in
Italian patients with schizophrenia, mood, and anxiety spectrum disorders.
AB - Latency to first pharmacological treatment [duration of untreated illness (DUI)]
in psychiatric disorders can be measured in years, with differences across
diagnostic areas and relevant consequences in terms of socio-occupational
functioning and outcome. Within the psychopathological onset of a specific
disorder, many factors influence access and latency to first pharmacotherapy and
the present study aimed to investigate such factors, through an ad-hoc developed
questionnaire, in a sample of 538 patients with diagnoses of schizophrenia
spectrum disorder (SZ), mood disorder (MD), and anxiety disorder (AD). Patients
with SZs showed earlier ages at onset, first diagnosis and treatment, as well as
shorter DUI compared with other patients (43.17 months vs. 58.64 and 80.43 months
in MD and AD; F=3.813, P=0.02). Patients with MD and AD reported more frequently
onset-related stressful events, benzodiazepines as first treatment, and
autonomous help seeking compared with patients with SZs. In terms of first
therapist, psychiatrist referral accounted for 43.6% of the cases, progressively
decreasing from SZ to MD and AD (57.6, 41.8, and 38.3%, respectively). The
opposite phenomenon was observed for nonpsychiatrist clinician referrals, whereas
psychologist referrals remained constant. The present findings confirm the
presence of a relevant DUI in a large sample of Italian patients with different
psychiatric disorders (5 years, on average), pointing out specific differences,
in terms of treatment access and latency, between psychotic and affective
patients. Such aspects are relevant for detection of at-risk patients and
implement early intervention programs.
PMID- 25117881
TI - Exercise and cardiovascular diseases.
AB - Exercise is a physiologic stressor that has multiple beneficial effects on
cardiovascular system. Currently exercise training is a class I intervention as
part of a multifactorial long-term process that includes: clinical assistance,
assessment of global cardiovascular risk, identification of specific objective
for each cardiovascular risk factor, formulation of an individual treatment plan
with multiple intervention aimed at reduction of the risk, educational programs,
planning of long term follow-up. This paper reviews the evidences of benefit of
exercise in the most common heart diseases and describes the role of exercise
training in the cardiac rehabilitation programs.
PMID- 25117880
TI - Renal denervation as a friend of catheter ablation in patients with atrial
fibrillation and hypertension.
PMID- 25117879
TI - An exploratory spatial analysis of geographical inequalities of birth intervals
among young women in the Democratic Republic of Congo (DRC): a cross-sectional
study.
AB - BACKGROUND: The length of time between two successive live births (birth
interval), is associated with child survival in the developing world. Short birth
intervals (<24 months) contribute to infant and child mortality risks.
Contraceptive use contributes to a reduction in short birth intervals, but
evidence is lacking in the DRC. We aimed to investigate the proportion of short
birth intervals at the provincial level among young women in the DRC. METHODS:
Data from the Demographic and Health Survey undertaken in the DRC in 2007 were
analyzed. Logistic regression and Bayesian geo-additive models were used to
explain provincial inequalities in short birth intervals among women of
reproductive age and young women. Posterior odds ratio (OR) and 95% credible
region (CR) were estimated via Markov chain Monte Carlo (MCMC) techniques.
Posterior spatial effects and the associated posterior probability maps were
produced at the provincial-level to highlight provinces with a significant higher
risk of short birth interval. RESULTS: The overall proportion of short birth
intervals among all women of reproductive age (15-49 years) and young women (15
24 years) were 30.2% and 38.7% respectively. In multivariate Bayesian geo
additive regression analyses, among the whole sample of women, living in rural
areas [OR = 1.07, 95% CR: (0.97, 1.17)], exclusive breastfeeding [1.08 (1.00,
1.17)] and women with primary education [1.06 (1.00, 1.16)], were consistently
associated with a higher risk of short birth intervals. For the young women, none
of the factors considered were associated with the risk of short birth interval
except a marginal effect from the lack of education. There was a spatial
variation in the proportion of women reporting short birth intervals and among
all women of reproductive age across provinces, with Nord-Kivu [1.12 (1.02,
1.24)], Sud Kivu [1.17 (1.05, 1.29)] and Kasai Occidental [1.18 (1.06, 1.32)]
reporting a higher risk of short birth intervals. For young women, the higher
risk provinces were Nord-Kivu [1.22 (1.00, 1.54)] and Sud Kivu [1.34 (1.14,
1.63)]. CONCLUSIONS: This study suggests distinct geographic patterns in the
proportion of short birth intervals among Congolese women, as well as the
potential role of demographic and geographic location factors driving the ongoing
higher youth fertility, higher childhood and maternal mortality in the DRC.
PMID- 25117882
TI - Changes in serum asymmetric dimethylarginine and endothelial markers levels with
varying periods of hemodialysis.
AB - Asymmetric dimethylarginine (ADMA) as a uremia toxin is accumulated in end-stage
renal disease (ESRD) patients. Elevated ADMA level has been shown to be
predictive of cardiovascular diseases (CVDs) and all-cause mortality in ESRD.
Therefore, we investigated the effect of prolonged hemodialysis (HD) treatment on
the levels of serum ADMA, arginine, nitric oxide (NO), soluble intercellular
adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1
(sVCAM-1). Seventy-five patients (M/F = 40/35) with chronic renal failure (CRF)
and who were on HD were divided into five groups with differing treatment periods
of HD; from 6 to 24 months to 97-120 months. Fifteen apparently healthy subjects
acted as controls. The serum levels of ADMA, sICAM-1 and sVCAM-1 were increased
in all patient groups compared to the control group. No significant difference
was observed when the patient groups were compared in terms of HD treatment
periods. Nitric oxide levels were lower in the three groups who were treated for
periods of 49-72, 73-96, 97-120 months compared to the control group. The L
arginine to ADMA ratio was decreased in all patient groups compared to controls.
Consequently, our investigations have shown that in HD continued for more than 4
years NO levels began to decrease significantly and the levels of serum ADMA,
sICAM-1 and sVCAM-1 levels increased although this increase was not affected by
the period in which hemodialysis treatment was applied.
PMID- 25117883
TI - New bone formation induced by minimodeling in a hemodialysis patient treated with
cinacalcet.
PMID- 25117887
TI - Determinants of modern family planning use among women of reproductive age in the
Nkwanta district of Ghana: a case-control study.
AB - BACKGROUND: Average contraceptive prevalence rate in the Nkwanta district of
Ghana was estimated to be 6.2% relative to the national average at the time, of
19%. While several efforts had been made to improve family planning in the
country, the district still had very low use of modern family planning methods.
This study sought to determine the factors that influenced modern family planning
use in general and specifically, the factors that determined the consistently low
use of modern family planning methods in the district. METHODS: A case-control
study was conducted in the Nkwanta district of Ghana to determine socio-economic,
socio-cultural and service delivery factors influencing family planning usage.
One hundred and thirty cases and 260 controls made up of women aged 15-49 years
were interviewed using structured questionnaires. A logistic regression was
fitted. RESULTS: Awareness and knowledge of modern family planning methods were
high among cases and controls (over 90%). Lack of formal education among women,
socio-cultural beliefs and spousal communication were found to influence modern
family planning use. Furthermore, favourable opening hours of the facilities and
distance to health facilities influenced the use of modern contraceptives.
CONCLUSION: While modern family planning seemed to be common knowledge among
these women, actual use of such contraceptives was limited. There is need to
improve use of modern family planning methods in the district. In addition to
providing health facilities and consolidating close-to-client service initiatives
in the district, policies directed towards improving modern family planning
method use need to consider the influence of formal education. Promoting basic
education, especially among females, will be a crucial step as the district is
faced with high levels of school dropout and illiteracy rates.
PMID- 25117886
TI - Effect of acute swim stress on plasma corticosterone and brain monoamine levels
in bidirectionally selected DxH recombinant inbred mouse strains differing in
fear recall and extinction.
AB - Stress-induced changes in plasma corticosterone and central monoamine levels were
examined in mouse strains that differ in fear-related behaviors. Two DxH
recombinant inbred mouse strains with a DBA/2J background, which were originally
bred for a high (H-FSS) and low fear-sensitized acoustic startle reflex (L-FSS),
were used. Levels of noradrenaline, dopamine, and serotonin and their metabolites
3,4-dihydroxyphenyacetic acid (DOPAC), homovanillic acid (HVA), and 5
hydroxyindoleacetic acid (5-HIAA) were studied in the amygdala, hippocampus,
medial prefrontal cortex, striatum, hypothalamus and brainstem. H-FSS mice
exhibited increased fear levels and a deficit in fear extinction (within-session)
in the auditory fear-conditioning test, and depressive-like behavior in the acute
forced swim stress test. They had higher tissue noradrenaline and serotonin
levels and lower dopamine and serotonin turnover under basal conditions, although
they were largely insensitive to stress-induced changes in neurotransmitter
metabolism. In contrast, acute swim stress increased monoamine levels but
decreased turnover in the less fearful L-FSS mice. L-FSS mice also showed a trend
toward higher basal and stress-induced corticosterone levels and an increase in
noradrenaline and serotonin in the hypothalamus and brainstem 30 min after stress
compared to H-FSS mice. Moreover, the dopaminergic system was activated
differentially in the medial prefrontal cortex and striatum of the two strains by
acute stress. Thus, H-FSS mice showed increased basal noradrenaline tissue levels
compatible with a fear phenotype or chronic stressed condition. Low
corticosterone levels and the poor monoamine response to stress in H-FSS mice may
point to mechanisms similar to those found in principal fear disorders or post
traumatic stress disorder.
PMID- 25117889
TI - School-level factors associated with increased fruit and vegetable consumption
among students in California middle and high schools.
AB - BACKGROUND: This study assessed associations between selective school-level
factors and students' consumption of fruits and vegetables at school. Better
understanding of school factors associated with increased produce consumption is
especially important, as students are served more produce items at school.
METHODS: This cross-sectional study included 5439 seventh- and ninth-grade
students from 31 schools in California in 2010. Multilevel regression models
estimated whether the odds of consuming fruits or vegetables at school among
students eating the school lunch were associated with the length of the lunch
period, quality/variety of produce options, or other factors. RESULTS: A longer
lunch period was associated with increased odds of a student eating fruits (odds
ratio [OR] = 1.40) and vegetables (OR = 1.54) at school. Better fruit quality
increased the odds of a student consuming fruit (OR = 1.44). Including a salad
bar and involving students in food service decisions increased a student's odds
of consuming vegetables (OR = 1.48 and OR = 1.34, respectively). CONCLUSIONS:
This study suggests that institutional factors in schools are positively
associated with middle and high school students' consumption of produce items at
school. Additional efforts to structure school meal environments to enhance
students' consumption of produce items can benefit students' nutrition and
health.
PMID- 25117888
TI - Relationship between frequency and intensity of cigarette smoking and TTFC/C
among students of the GYTS in select countries, 2007-2009.
AB - BACKGROUND: This study assessed the construct validity of a measure of nicotine
dependence that was used in the Global Youth Tobacco Survey (GYTS). METHODS:
Using 2007-2009 data from the GYTS, subjects from 6 countries were used to assess
current smokers' odds of reporting time to first cigarette or craving positive
(TTFC/C+) by the number of cigarette smoking days per month (DPM) and the number
of cigarettes smoked per day (CPD). RESULTS: The percentage of GYTS smokers who
reported TTFC/C+ ranged from 58.0% to 69.7%. Compared with students who smoked on
1-2 DPM, those who smoked on 3-9 DPM had 3 times the adjusted odds of reporting
TTFC/C+. The adjusted odds of reporting TTFC/C+ were 3 to 7 times higher among
those who smoked 10-29 DPM and 6 to 20 times higher among daily smokers.
Similarly, the adjusted odds of TTFC/C+ were 3-6 times higher among those who
smoked 2-5 CPD and 6 to 20 times higher among those who smoked >6 CPD, compared
to those who smoked <1 CPD. CONCLUSION: Associations of TTFC/C+ prevalence with
both frequency and intensity of cigarette smoking provide a construct validation
of the GYTS question used to assess respondents' TTFC/C status.
PMID- 25117890
TI - Classroom carbon dioxide concentration, school attendance, and educational
attainment.
AB - BACKGROUND: We tested the hypothesis that classroom carbon dioxide (CO2 )
concentration is inversely related to child school attendance and educational
attainment. METHODS: Concentrations of CO2 were measured over a 3-5 day period in
60 naturally ventilated classrooms of primary school children in Scotland.
Concentrations of CO2 were related to the class average annual attendance and
proportions attaining a national standard for reading, writing, and numeracy,
adjusted for socioeconomic status and class size. RESULTS: The median
(interquartile range, IQR) CO2 concentration averaged over the school day was
1086 ppm (922, 1310). In the model, Time Weighted Average CO2 concentrations were
inversely associated with school attendance but not academic attainments. An
increase of 100 ppm CO2 was associated with a reduced annual attendance of 0.2%
(0.04, 0.4) roughly equivalent to 1 half day of school per annum, assuming
schools are open on 190 days per year. Indoor temperature and relative humidity
were not related to attendance or academic attainment. CONCLUSIONS: Inadequate
classroom ventilation, as evidenced by CO2 concentration exceeding 1000 ppm, is
not uncommon and may be associated with reduced school attendance. A relationship
between inadequate classroom ventilation and adverse health outcomes in children
may be present and this needs to be explored.
PMID- 25117891
TI - School bus crash rates on routine and nonroutine routes.
AB - BACKGROUND: Although prior research has established that school buses are a safe
form of transportation, crashes can produce catastrophic consequences. School
buses have 2 types of routes: predictable, routine routes that take children to
and from school and less predictable, nonroutine routes for school events. No
studies have examined school bus crash incidence and characteristics by these
route types. METHODS: School bus crashes were identified from the Iowa Department
of Transportation Crash Database from mid-2005 through mid-2010. Crash reports
did not identify whether the bus was on a routine or nonroutine route, so a
protocol to assign these based on day and time was developed. Bus mileage was
provided by the Iowa Department of Education. RESULTS: The school bus crash rate
was 2.1 times higher on nonroutine routes than on routine routes (95% CI = 1.8
2.3). Most crashes involved an improper action by the driver of another vehicle.
In crashes attributed to improper actions of school buses, failure to yield the
right-of-way and disregarding traffic signs were more common on routine routes,
while losing control, speeding, reckless, or aggressive driving were more common
on nonroutine routes. CONCLUSIONS: School bus crashes are more likely to occur on
nonroutine routes.
PMID- 25117892
TI - The "ins" and "outs" of physical activity policy implementation: inadequate
capacity, inappropriate outcome measures, and insufficient funds.
AB - BACKGROUND: Despite broad public support and legislative activity, policies
intended to promote physical activity in schools have not produced positive
outcomes in levels of physical activity or student health. What explains the
broad failure of Physical Activity Policies (PAPs)? Thus far, PAP research has
used limited quantitative methods to assess PAP outcomes. New paradigms of
qualitative policy implementation research can make important contributions to
explaining the causes of policy failure and to the future design of more
efficacious PAP legislation. METHODS: This analysis is a case study of South
Carolina's 2005 Student Health and Fitness Act (SHFA). Written documents,
investigators' observation and experience, and an interview with a key
stakeholder were analyzed to for themes based on theoretical frameworks from
education implementation research including (1) bottom-up and top-down
perspectives, (2) conceptualizing policy as practice, and (3) the implementer as
learner. RESULTS: "Weak policy signals" in SHFA undermined the implementation of
PAP in 3 problematic areas: inadequate capacity development for implementers,
inappropriate measures of implementation, and insufficient funding. CONCLUSIONS:
These findings illustrate the contributions of qualitative research and establish
the need for further qualitative research into PAP implementation processes. To
ensure successful future physical activity policies, policymakers, and
stakeholders need to consider implementation, evaluation, and funding from the
beginning phases of policy development.
PMID- 25117893
TI - Influenza vaccination coverage among school employees: assessing knowledge,
attitudes, and behaviors.
AB - BACKGROUND: Influenza can spread among students, teachers, and staff in school
settings. Vaccination is the most effective method to prevent influenza. We
determined 2012-2013 influenza vaccination coverage among school employees,
assessed knowledge and attitudes regarding the vaccine, and determined factors
associated with vaccine receipt. METHODS: We surveyed 412 (49%) of 841 employees
at 1 suburban Ohio school district in March 2013. The Web-based survey assessed
personal and work characteristics, vaccine receipt, and knowledge and attitudes
regarding the vaccine. RESULTS: Overall, 238 (58%) respondents reported getting
the 2012-2013 influenza vaccine. The most common reason for getting the vaccine
was to protect oneself or one's family (87%). Beliefs that the vaccine was not
needed (32%) or that it was not effective (21%) were the most common reasons for
not getting it. Factors independently associated with vaccine receipt were having
positive attitudes toward the vaccine, feeling external pressure to get it, and
feeling personal control over whether to get it. CONCLUSIONS: Influenza vaccine
coverage among school employees should be improved. Messages encouraging school
employees to get the vaccine should address misconceptions about the vaccine.
Employers should use methods to maximize employee vaccination as part of a
comprehensive influenza prevention program.
PMID- 25117894
TI - Measuring school climate in high schools: a focus on safety, engagement, and the
environment.
AB - BACKGROUND: School climate has been linked to multiple student behavioral,
academic, health, and social-emotional outcomes. The US Department of Education
(USDOE) developed a 3-factor model of school climate comprised of safety,
engagement, and environment. This article examines the factor structure and
measurement invariance of the USDOE model. METHODS: Drawing upon 2 consecutive
waves of data from over 25,000 high school students (46% minority), a series of
exploratory and confirmatory factor analyses examined the fit of the Maryland
Safe and Supportive Schools Climate Survey with the USDOE model. RESULTS: The
results indicated adequate model fit with the theorized 3-factor model of school
climate, which included 13 subdomains: safety (perceived safety, bullying and
aggression, and drug use); engagement (connection to teachers, student
connectedness, academic engagement, school connectedness, equity, and parent
engagement); environment (rules and consequences, physical comfort, and support,
disorder). We also found consistent measurement invariance with regard to student
sex, grade level, and ethnicity. School-level interclass correlation coefficients
ranged from 0.04 to .10 for the scales. CONCLUSIONS: Findings supported the USDOE
3-factor model of school climate and suggest measurement invariance and high
internal consistency of the 3 scales and 13 subdomains. These results suggest the
56-item measure may be a potentially efficient, yet comprehensive measure of
school climate.
PMID- 25117895
TI - Employment status among parenting teenage mothers enrolled in high school.
AB - BACKGROUND: Many programs emphasize subsequent pregnancy prevention and high
school graduation among teenage mothers; however, less is known about their
ability to increase financial earnings from employment opportunities while
concurrently enrolled in school. This study evaluates factors influencing
employment status among teenage mothers after enrolling in a community-based
randomized intervention. METHODS: Project Mothers and Schools (PMAS) initiative
participants were surveyed at baseline and 12 months after enrollment. The 56
control group participants received homebound education and family case
management, whereas the 59 intervention group participants received these basic
level services as well as group parenting time, life skills, and leadership
training. A generalized estimating equation was used to identify statistically
significant changes associated with the intervention. RESULTS: Participants were
significantly more likely to receive money from their jobs at postintervention
relative to baseline (OR = 4.75, p = .023); however, this change was not
statistically significant when comparing the control group to the intervention
group. At postintervention, those who received money from parents were
significantly less likely to receive money from their job (OR = 0.12, p = .002).
CONCLUSIONS: While PMAS benefited participants in terms of employment, the role
of parental support requires additional investigation to determine its influence
on teenage mothers' ability to achieve financial independence.
PMID- 25117896
TI - State-level school competitive food and beverage laws are associated with
children's weight status.
AB - BACKGROUND: This study attempted to determine whether state laws regulating low
nutrient, high energy-dense foods and beverages sold outside of the reimbursable
school meals program (referred to as "competitive foods") are associated with
children's weight status. METHODS: We use the Classification of Laws Associated
with School Students (CLASS) database of state codified law(s) relevant to school
nutrition. States were classified as having strong, weak, or no competitive food
laws in 2005 based on strength and comprehensiveness. Parent-reported height and
weight along with demographic, behavioral, family, and household characteristics
were obtained from the 2007 National Survey of Children's Health. Bivariate and
logistic regression analyses estimated the association between states'
competitive food laws and children's overweight and obesity status (body mass
index [BMI]-for-age >=85th percentile). Children (N = 16,271) between the ages of
11-14 years with a BMI for age >=5th percentile who attended public school were
included. RESULTS: Children living in states with weak competitive food laws for
middle schools had over a 20% higher odds of being overweight or obese than
children living in states with either no or strong school competitive food laws.
CONCLUSION: State-level school competitive food and beverage laws merit attention
with efforts to address the childhood obesity epidemic. Attention to the
specificity and requirements of these laws should also be considered.
PMID- 25117897
TI - Characterization of Coffee ringspot virus-Lavras: a model for an emerging threat
to coffee production and quality.
AB - The emergence of viruses in Coffee (Coffea arabica and Coffea canephora), the
most widely traded agricultural commodity in the world, is of critical concern.
The RNA1 (6552nt) of Coffee ringspot virus is organized into five open reading
frames (ORFs) capable of encoding the viral nucleocapsid (ORF1p), phosphoprotein
(ORF2p), putative cell-to-cell movement protein (ORF3p), matrix protein (ORF4p)
and glycoprotein (ORF5p). Each ORF is separated by a conserved intergenic
junction. RNA2 (5945nt), which completes the bipartite genome, encodes a single
protein (ORF6p) with homology to RNA-dependent RNA polymerases. Phylogenetic
analysis of L protein sequences firmly establishes CoRSV as a member of the
recently proposed Dichorhavirus genus. Predictive algorithms, in planta protein
expression, and a yeast-based nuclear import assay were used to determine the
nucleophillic character of five CoRSV proteins. Finally, the temperature
dependent ability of CoRSV to establish systemic infections in an initially local
lesion host was quantified.
PMID- 25117898
TI - Circulating levels of chemokines in psoriasis.
AB - Chemokines may contribute to local and systemic inflammation in patients with
psoriasis. Previous studies have demonstrated the importance of chemokine ligands
and receptors in the recruitment of T cells into psoriatic lesional skin and
synovial fluid. The aim of this study was to evaluate the levels of Th1-related
chemokines in psoriasis and to investigate any association with disease severity.
We quantified serum levels of CXCL9, CXCL10 and CXCL16 and the frequencies of
CD4+CXCR3+ T lymphocytes through ELISA and flow cytometry, respectively. A total
of 38 patients with psoriasis and 33 controls were included. There were no
significant differences in chemokine levels between psoriasis and control groups.
Patients with psoriatic arthritis had lower median level of CXCL10 when compared
with controls (p=0.03). There were no significant correlations between serum
chemokines analyzed and disease severity. Frequencies of CD4+CXCR3+ T cells were
lower in patients with psoriasis than in controls (p<0.01). A sensitivity
analysis excluding patients on systemic therapy yielded similar results. Serum
concentrations of CXCL9, CXCL10 and CXCL16 were not increased in the psoriasis
group or correlated with disease severity. Systemic levels of chemokine ligands
do not seem to be sensitive biomarkers of disease activity or accurate parameters
to predict response to therapy. Frequencies of CD4+CXCR3+ T cells were decreased
in the peripheral blood of psoriasis patients, possibly due to recruitment to
inflammatory lesions.
PMID- 25117899
TI - NMR characterization of the electrostatic interaction of the basic residues in
HDGF and FGF2 during heparin binding.
AB - Electrostatic interaction is a major driving force in the binding of proteins to
highly acidic glycosaminoglycan, such as heparin. Although NMR backbone chemical
shifts have generally been used to identify the heparin-binding site on a
protein, however, there is no correlation between the binding free energies and
the perturbed backbone chemical shifts for individual residues. The binding event
occurs at the end of a side chain of basic residue, and does not require causing
significant alterations in the backbone environment at a distance of multiple
bonds. We used the H2CN NMR pulse sequence to detect heparin binding through the
side-chain resonances Hepsilon-Cepsilon-Nzeta of Lys and Hdelta-Cdelta-Nepsilon
of Arg in the two proteins of hepatoma-derived growth factor (HDGF) and basic
fibroblast growth factor (FGF2). H2CN titration experiments revealed chemical
shift perturbations in the side chains, which were correlated with the free
energy changes in various mutants. The residues K19 in HDGF and K125 in FGF2
demonstrated the most significant perturbations, consistent with our previous
observation that the two residues are crucial for binding. The result suggests
that H2CN NMR provides a precise evaluation for the electrostatic interactions.
The discrepancy observed between backbone and side chain chemical shifts is
correlated to the solvent accessibility of residues that the K19 and K125
backbones are highly buried with the restricted backbone conformation and are not
strongly affected by the events at the end of the side chains.
PMID- 25117905
TI - Bevacizumab revisited: its use in different mouse models of ocular pathologies.
AB - PURPOSE: Previous reports have yielded conflicting data on the activity of
bevacizumab (Avastin), a recombinant humanized monoclonal antibody against VEGF
A, in the mouse. The current study was designed to further explore the use of
this VEGF inhibitor in various murine models of ocular diseases and compare it to
the widely used murine anti-VEGF-R2 neutralizing antibody (DC101). METHODS:
Murine models of laser-induced choroidal neovascularization (CNV), oxygen-induced
retinopathy (OIR) and glaucoma filtration surgery (GFS) were used to investigate
the effect of bevacizumab. Mice either received an intravitreal (CNV-OIR) or
subconjunctival (GFS) injection. In all models, they were divided in two groups
(n = 10 per group). In the first group, one eye was injected with bevacizumab (1
ul; 25 ug) and the other eye was used as a negative control and received an
injection of NaCl (1 ul; 0.9%). In the second group, one eye was injected with
DC101 (1 ul; 6.2 ug), whereas an isotype-matched control antibody (1C8; 4.8 ug)
was administered in the contralateral eye. Treatment outcome was studied by
clinical investigation (GFS) and immunohistological analysis of angiogenesis
(CD31/FITC-dextran/H&E) and fibrosis (Sirius Red). RESULTS: Analysis of blood
vessel density (CNV) and blood vessel growth (OIR) showed a comparable decrease
after intravitreal administration of bevacizumab or DC101. Furthermore, in the
mouse model of GFS, clinical investigation of the bleb and a CD31 staining on
sections demonstrated that subconjunctival injection of both antibodies similarly
improved the surgical outcome (bleb area and survival) by reducing angiogenesis.
Moreover, morphometric analysis after Sirius Red staining showed a comparable
reduction in collagen deposition after administration of the inhibitors.
CONCLUSION: Our findings consistently demonstrate that bevacizumab is as
effective as the murine anti-VEGF-R2 antibody (DC101) in mouse models of CNV, OIR
and GFS, thus confirming its suitability for translational ophthalmological
research.
PMID- 25117906
TI - Erlotinib and gastric acid-reducing agents: a combination to avoid or to support?
PMID- 25117907
TI - Bayes factor for investigative assessment of selected handwriting features.
AB - This paper extends previous research on the use of multivariate continuous data
in comparative handwriting examinations, notably for gender classification. A
database has been constructed by analyzing the contour shape of loop characters
of type a and d by means of Fourier analysis, which allows characters to be
described in a global way by a set of variables (e.g., Fourier descriptors).
Sample handwritings were collected from right- and left-handed female and male
writers. The results reported in this paper provide further arguments in support
of the view that investigative settings in forensic science represent an area of
application for which the Bayesian approach offers a logical framework. In
particular, the Bayes factor is computed for settings that focus on inference of
gender and handedness of the author of an incriminated handwritten text. An
emphasis is placed on comparing the efficiency for investigative purposes of
characters a and d.
PMID- 25117908
TI - Quantitative evaluation of the performance of a new test bolus-based computed
tomographic angiography contrast-enhancement-prediction algorithm.
AB - OBJECTIVES: The objective of this study was to assess the robustness of a novel
test bolus (TB)-based computed tomographic angiography (CTA) contrast-enhancement
prediction (CEP) algorithm by retrospectively quantifying the systematic and
random errors between the predicted and true enhancements. MATERIALS AND METHODS:
All local institutional review boards approved this retrospective study, in which
a total of 72 (3 * 24) anonymized cardiac CTA examinations were collected from 3
hospitals. All patients (46 men; median age, 62 years [range, 31-81 years])
underwent a TB scan and a cardiac CTA according to local scan and injection
protocols. For each patient, a shorter TB signal and TB signals with lower
temporal resolution were derived from the original TB signal. The CEP algorithm
predicted the enhancement in the descending aorta (DAo) on the basis of the TB
signals in the DAo, the injection protocols and kilovolt settings, as well as
population-averaged blood circulation characteristics. The true enhancement was
extracted with a region of interest along the DAo centerline. For each patient,
the errors in timing and amplitude were calculated; differences between the
hospitals were assessed using the 1-way analysis of variance (P < 0.05) and
variations between the TB signals were assessed using the within-subject standard
deviation. RESULTS: No significant differences were found between the 3 hospitals
for any of the TB signals. With errors in the amplitude and timing of 0.3% +/-
15.6% and -0.2 +/- 2.0 seconds, respectively, no clinically relevant systematic
errors existed. Shorter- and coarser-time-sampled TB signals introduced a within
subject standard deviation of 4.0% and 0.5 seconds, respectively. CONCLUSIONS:
This TB-based CEP algorithm has no systematic errors in the timing and amplitude
of predicted enhancements and is robust against coarser-time-sampled and
incomplete TB scans.
PMID- 25117909
TI - Physical activity in chronic kidney disease: a plausible approach to vascular
calcification?
AB - Vascular calcification (VC) is a prominent feature that affects up to 40 to 80%
of Chronic Kidney Disease (CKD) patients depending on the degree of renal
impairment. Though etiology and pathogenesis of the different types of VC are far
from being elucidated, it is conceivable that an imbalance between promoters and
inhibitors represents the condition that triggers VC deposition and progression.
In addition to traditional cardiovascular risk factors, several lines of evidence
suggest that specific factors may affect the arterial system and prognosis in
CKD. Over the last decade, a few pharmacological strategies aimed at controlling
different selected risk factors for VC have been investigated yielding
conflicting results. In light of the complicated interplay between inhibitors and
promoters as well as the fact that VC represents the result of cumulative and
prolonged exposure to multiple risk factors, a more comprehensive risk
modification approach such as lifestyle modification or physical activity (PA)
may represent a valid strategy to attenuate VC deposition and progression.We
herein aim at reviewing the rationale and current evidence on the potential for
lifestyle modification with a specific focus on PA as a cost-effective strategy
for VC treatment.
PMID- 25117911
TI - Part I: frequency of depression after stroke: an updated systematic review and
meta-analysis of observational studies.
AB - BACKGROUND: Approximately 15 million people who suffer a stroke globally each
year are at risk of developing depression. AIM: To update our systematic review
and meta-analysis of the frequency of depression after stroke published in 2005,
including studies published before July 2004. METHODS: We included all published
observational studies (to 31 May 2013) with prospective consecutive recruitment
and quantification of the proportion of people with depression after stroke. We
included studies of adult (>18 years) patients with a clinical diagnosis of
stroke, where an assessment of depression or depressive symptom burden was
performed at a pre-specified time-point for all study participants. RESULTS: Data
were available from 61 studies including 25,488 people. The proportional
frequency of depression varied considerably across studies; however, the pooled
frequency estimate of 31% (95% confidence interval 28% to 35%) was not
significantly different from the 33% (difference of 2%, 95% confidence interval
<1% to 3%) reported in the 2005 review. The proportion with depression between
one and five-years (25%; 95% confidence interval 16 to 33%) and at five years
after stroke (23%; 95% confidence interval 14 to 31%) was significantly lower.
CONCLUSION: Despite systematic review evidence describing validated depression
screening tools and effective treatment and prevention strategies for depression
after stroke, there has not been a significant reduction in the proportion of
people experiencing depression after stroke. There is a pressing need for
increased clinical uptake of evidenced-based strategies to screen for, prevent,
and treat depression after stroke.
PMID- 25117910
TI - Anti-peroxynitrite treatment ameliorated vasorelaxation of resistance arteries in
aging rats: involvement with NO-sGC-cGKs pathway.
AB - Declined vasorelaxation function in aging resistance arteries is responsible for
aging-related multiple organ dysfunctions. The aim of the present study is to
explore the role of peroxynitrite (ONOO-) in aging resistance arterial
vasorelaxation dysfunction and the possible mechanism. In the present study,
young (3-4 months olds) and aging (20 months olds) male SD rats were randomized
to receive vehicle (Saline) or FeTMPyP (ONOO- scavenger) for 2 weeks. The
vasorelaxation of resistance arteries was determined in vitro; NOx level was
tested by a colorimetric assay; the expression of nitrotyrosine (NT), soluble
Guanylate Cyclase (sGC), vasodilator-stimulated phosphoprotein (VASP),
phosphorylated VASP (P-VASP) and cGMP in resistance arteries were detected by
immunohistochemical staining. In the present study, endothelium-dependent
dilation in aging resistance arteries was lower than in those from young rats
(young vs. aging: 68.0% +/- 4.5% vs. 50.4% +/- 2.9%, P<0.01). And the endothelium
independent dilation remained constant. Compared with young rats, aging increased
nitrative stress in resistance arteries, evidenced by elevated NOx production in
serum (5.3 +/- 1.0 nmol/ml vs. 3.3 +/- 1.4 nmol/ml, P<0.05) and increased NT
expression (P<0.05). ONOO- was responsible for the vasorelaxation dysfunction,
evidenced by normalized vasorelaxation after inhibit ONOO- or its sources
(P<0.05) and suppressed NT expression after FeTMPyP treatment (P<0.05). The
expression of sGC was not significantly different between young and aging
resistance arteries, but the cGMP level and P-VASP/VASP ratio (biochemical marker
of NO-sGC-cGKs signaling) decreased, which was reversed by FeTMPyP treatment in
vivo (P<0.05). The present study suggested that ONOO- mediated the decline of
endothelium-dependent vasorelaxation of aging resistance arteries by induction of
the NO-sGC-cGKs pathway dysfunction.
PMID- 25117913
TI - Oral administration of the AYA strain of Lactobacillus plantarum modulates
expression of immunity-related genes in the murine Peyer's patch: a DNA
microarray analysis.
AB - We performed comprehensive transcriptome analysis of Peyer's patches to elucidate
the effects of oral administration of Lactobacillus plantarum strain AYA in mice.
Using microarray analysis, we identified 124 upregulated and 144 downregulated
genes for four weeks after the start of dietary supplementation with AYA. Gene
Ontology analysis revealed that the genes for immune function were enriched in
the upregulated gene set.
PMID- 25117912
TI - Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell
lymphoma patients: a population-based analysis.
AB - BACKGROUND: Current treatment of diffuse-large-B-cell lymphoma (DLBCL) includes
rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin,
vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted
rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as
first-line treatment of DLBCL, but it remains unclear what its real-world costs
and cost-effectiveness are in routine clinical practice. METHODS: We performed a
population-based retrospective cohort study from 1997 to 2007, using linked
administrative databases in Ontario, Canada, to evaluate the costs and cost
effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n =
1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on
age and treatment intensity and then propensity-score matched on sex,
comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were
adjusted for censoring using the inverse probability weighting method. The main
outcome measure was incremental cost per life-year gained (LYG). RESULTS:
Rituximab was associated with a life expectancy increase of 3.2 months over 5
years at an additional cost of $16,298, corresponding to an incremental cost
effectiveness ratio of $61,984 (95% CI $34,087-$135,890) per LYG. The probability
of being cost-effective was 90% if the willingness-to-pay threshold was
$100,000/LYG. The cost-effectiveness ratio was most favourable for patients less
than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79
years old and $110,100/LYG for patients >= 80 years old. We found that post
market survival benefits of rituximab are similar to or lower than those reported
in clinical trials, while the costs, incremental costs and cost-effectiveness
ratios are higher than in published economic models and differ by age.
CONCLUSIONS: Our results showed that the addition of rituximab to standard CHOP
chemotherapy was associated with improvement in survival but at a higher cost,
and was potentially cost-effective by standard thresholds for patients <60 years
old. However, cost-effectiveness decreased significantly with age, suggesting
that rituximab may be not as economically attractive in the very elderly on
average. This has important clinical implications regarding age-related use and
funding decisions on this drug.
PMID- 25117915
TI - Phenotypic and genetic evidence for ecological speciation of Aquilegia japonica
and A. oxysepala.
AB - Natural selection is thought to be a driving force that can cause the evolution
of reproductive isolation. The genus Aquilegia is a model system to address how
natural selection promotes the process of speciation. Morphological differences
between A. oxysepala, A. japonica and their hybrids were quantified for two
vegetative (plant height and leaf area) and three floral morphological (sepal
area, corolla length and diameter) traits. We also evaluated the genetic
variability of the two species and their hybrids based on two chloroplast (1225
bp), four nuclear (5811 bp) genes and 15 microsatellites. Our results revealed
that differentiation of A. japonica and A. oxysepala at the ecological and
morphological levels also involved divergence at the genetic level. In addition,
the analysis of nucleotide variation patterns showed that the two species
possessed numerous fixation sites at nuclear genes gAA4, gA7 and gAA12.
Furthermore, we found that all of the phenotypic hybrids also showed a
genetically admixed ancestry. These findings suggest that natural selection has
indeed facilitated the formation of distinct genetic variation patterns in the
two Aquilegia species and habitat adaptation has been driving the ecologically
based evolution of reproductive isolation.
PMID- 25117916
TI - Kaiser Permanente's commitment to breastfeeding.
PMID- 25117914
TI - Shotgun approaches to gait analysis: insights & limitations.
AB - BACKGROUND: Identifying features for gait classification is a formidable problem.
The number of candidate measures is legion. This calls for proper, objective
criteria when ranking their relevance. METHODS: Following a shotgun approach we
determined a plenitude of kinematic and physiological gait measures and ranked
their relevance using conventional analysis of variance (ANOVA) supplemented by
logistic and partial least squares (PLS) regressions. We illustrated this
approach using data from two studies involving stroke patients, amputees, and
healthy controls. RESULTS: Only a handful of measures turned out significant in
the ANOVAs. The logistic regressions, by contrast, revealed various measures that
clearly discriminated between experimental groups and conditions. The PLS
regression also identified several discriminating measures, but they did not
always agree with those of the logistic regression. DISCUSSION & CONCLUSION:
Extracting a measure's classification capacity cannot solely rely on its
statistical validity but typically requires proper post-hoc analysis. However,
choosing the latter inevitably introduces some arbitrariness, which may affect
outcome in general. We hence advocate the use of generic expert systems, possibly
based on machine-learning.
PMID- 25117917
TI - Mental health trajectories and their embeddedness in work and family
circumstances: a latent state-trait approach to life-course trajectories.
AB - Mental health trajectories are known to be influenced by work and family
circumstances. However, few studies have examined both of these influences
simultaneously in a longitudinal manner. The life-course perspective stresses the
importance of examining trajectories in terms of both stable and dynamic
components. In this article we use structural equation models (latent state
trait, LST) to distinguish the stable and situational components of mental health
trajectories and hypothesise that situational mental health is influenced by
satisfaction with work and family, and this effect differs by gender. An analysis
of data from a nationally representative sample of 1616 working Swiss residents
(2000-2006) shows that mental health trajectories are mostly stable and only
slightly sensitive to situational influences. However, situational influences in
a given wave do predict situational influences in the next wave. Satisfaction
with work and family influences situational mental health in both genders, but
the impact is greater for men. In conclusion, the LST approach allows for the
examination of mental health trajectories from a life-course perspective by
distinguishing stable and situational components. Mental health trajectories are
more stable and constant than they are dependent on work and family
circumstances, and men are more sensitive to family circumstances than women.
PMID- 25117918
TI - The placebo effect in early-phase glaucoma clinical trials.
AB - PURPOSE: To analyze the extent and prevalence of the placebo effect in prior
early-phase glaucoma clinical studies. METHODS: Articles were evaluated on phase
I and II trials of glaucoma medicines that became commercially available after
1977 with a placebo arm that involved glaucoma patients. RESULTS: We included 23
studies with 23 treatment arms with a total of 1703 patients in articles
evaluating 10 different glaucoma medications. This study showed that at 8 AM (n =
18), the average decrease in placebo from untreated baseline was 2.3 +/- 1.6 mm
Hg (9%), while for the diurnal curve (n = 17), the mean decrease was 1.4 +/- 1.1
mm Hg (6%). At 8 AM, 8/18 treatment arms had greater than 2 mm Hg intraocular
pressure (IOP) decrease, and all had at least some reduction in IOP. For the
diurnal curve, 4 of 17 studies had reduced IOP greater than 2 mm Hg. One
treatment arm had no placebo effect. CONCLUSIONS: This study suggests that a
placebo effect is common in glaucoma clinical trials and potentially could limit
the ability to evaluate the efficacy of a new medicine.
PMID- 25117919
TI - Frailty, disability and physical exercise in the aging process and in chronic
kidney disease.
AB - Frailty in the elderly is a state of vulnerability to poor resolution of
homoeostasis after a stressor event and is a consequence of cumulative decline in
many physiological systems during a lifetime. This cumulative decline depletes
homoeostatic reserves until minor stressor events trigger disproportionate
changes in health status. It is usually associated to adverse health outcomes and
to one-year mortality risk. Physical exercise has found to be effective in
preventing frailty and disability in this population. Chronic kidney disease
(CKD) is also a clinical condition where protein energy-wasting, sarcopenia and
dynapenia ,very common symptoms in the frail elderly, may occur. Moreover elderly
and CKD patients are both affected by an impaired physical performance that may
be reversed by physical exercise with an improvement of the survival rate. These
similarities suggest that frailty may be a common pathway of aging and CKD that
may induce disability and that can be prevented by a multidimensional approach in
which physical exercise plays an important role.
PMID- 25117928
TI - Impact of 5-aminolevulinic acid fluorescence-guided surgery on the extent of
resection of meningiomas--with special regard to high-grade tumors.
AB - BACKGROUND AND OBJECTIVES: In high-grade meningiomas and a subgroup of clinically
aggressive benign meningiomas tumor control is still insufficient. Recently 5-ALA
fluorescence in meningiomas was reported. The impact of 5-ALA fluorescence-guided
surgery (FGS) on surgical decision-making and extent of resection has not yet
been systematically analyzed, especially not in high-grade meningiomas. The
present study deals with three main questions regarding 5-ALA FGS in meningiomas:
to assess the potential for discriminating different WHO grades intra
operatively, to analyze the influence on surgical strategy and to evaluate the
impact on extent of resection. METHODS: Data from 31 meningiomas operated with 5
ALA FGS were retrospectively analyzed. Intraoperative fluorescence was graded by
the surgeon as "no", "low" or "high". Correlations between semi-quantitative
fluorescence and histological features (WHO grade) were analyzed. The influence
of 5-ALA fluorescence on surgical strategy and the impact of 5-ALA FGS on degree
of resection (Simpson grade and post-operative imaging) were studied. In tumors
showing infiltrative growth the extent of resection of fluorescence positive
tissue was evaluated. RESULTS: The population comprised 19 WHO grade I, 8 grade
II and 4 grade III tumors (61% benign and 39% high-grade meningiomas). 94% of the
tumors showed positive fluorescence. Different fluorescence intensities were
observed: "no" in two, "high" in 12 and "low" in 17 tumors, respectively. A
significant correlation between fluorescence intensity and WHO grade was found
(rho=0.557, p=0.001). 5-ALA improved the extent of resection in 3/16 (19%) of
grade I and in 6/8 (75%) of grade II/III meningiomas. This improvement was not
measurable by the Simpson grading as rated by the surgeon and controlled on post
operative imaging. CONCLUSIONS: In the present population a strong correlation
between fluorescence intensity and WHO grade was observed. 5-ALA FGS improved the
extent of resection in meningiomas. Especially in high-grade tumors additional
information on brain and neurovascular infiltration was provided. The improved
resection was not measurable by Simpson's grading necessitating an additional
item, which rates residual fluorescence. Long-term studies are necessary to
evaluate a possible impact of FGS on recurrence and overall survival.
PMID- 25117920
TI - Can trained volunteers make a difference at mealtimes for older people in
hospital? A qualitative study of the views and experience of nurses, patients,
relatives and volunteers in the Southampton Mealtime Assistance Study.
AB - BACKGROUND: Malnutrition is common amongst hospitalised older patients and
associated with increased morbidity and mortality. Poor dietary intake results
from factors including acute illness and cognitive impairment but additionally
patients may have difficulty managing at mealtimes. Use of volunteers to help at
mealtimes is rarely evaluated. OBJECTIVES: To obtain multiple perspectives on
nutritional care of older inpatients, acceptability of trained volunteers and
identify important elements of their assistance. DESIGN: A qualitative study 1
year before and after introduction of volunteer mealtime assistants on one ward
and parallel comparison with a control ward in a Medicine for Older People
department at a UK university hospital. PARTICIPANTS AND METHODS: Semi-structured
interviews and focus groups, in baseline and intervention years, with purposively
sampled nursing staff at different levels of seniority; patients or close
relatives; and volunteers. RESULTS: At baseline staff felt under pressure with
insufficient people assisting at mealtimes. Introducing trained volunteers was
perceived by staff and patients to improve quality of mealtime care by preparing
patients for mealtimes, assisting patients who needed help, and releasing nursing
time to assist dysphagic or drowsy patients. There was synergy with other
initiatives, notably protected mealtimes. Interviews highlighted the perceived
contribution of chronic poor appetite and changes in eating patterns to risk of
malnutrition. CONCLUSIONS: Improved quality of mealtime care attributed to
volunteers' input has potential to enhance staff morale and patients'/relatives'
confidence. A volunteer mealtime assistance scheme may work best when introduced
in context of other changes reflecting commitment to improving nutrition.
IMPLICATIONS FOR PRACTICE: (i) A mealtime assistance scheme should incorporate
training, supervision and support for volunteers; (ii) Good relationships and a
sense of teamwork can develop between wards staff and volunteers; (iii) Impact
may be maximised in the context of 'protected mealtimes'.
PMID- 25117930
TI - Ethical considerations in HIV prevention and vaccine research in resource-limited
settings.
AB - HIV prevention research has been facing increasing ethical and operational
challenges. Factors influencing the design and conduct of HIV prevention trials
include a rapidly changing evidence base, new biomedical prevention methods and
modalities being tested, a large diversity of countries, sites and populations
affected by HIV and participating in trials, and challenges of developing and
making available products that will be feasible and affordable for at-risk
populations. To discuss these challenges, a meeting, Ethical considerations
around novel combination prevention modalities in HIV prevention and vaccine
trials in resource-limited settings, was convened by NIH/NIAID/Division of AIDS
on April 22-23, 2013. Several themes emerged from the meeting: (1) because of
both trial design and ethical complexities, choosing prevention packages and
designing combination prevention research trials will need to be evaluated on a
case by case basis in different clinical trials, countries, and health systems;
(2) multilevel stakeholder engagement from the beginning is vital to a fair and
transparent process and also to designing ethical and relevant trials; (3)
research should generally be responsive to a host country's needs, and sponsors
and stakeholders should work together to address potential barriers to future
access; and finally, (4) another meeting including a broader group of
stakeholders is needed to address many of the outstanding ethical issues raised
by this meeting. We offer an overview of the meeting and the key discussion
points and recommendations to help guide the design and conduct of future HIV
prevention and vaccine research in resource-limited settings.
PMID- 25117933
TI - Improvement of ligninolytic properties by recombinant expression of glyoxal
oxidase gene in hyper lignin-degrading fungus Phanerochaete sordida YK-624.
AB - Glyoxal oxidase (GLOX) is a source of the extracellular H2O2 required for the
oxidation reactions catalyzed by the ligninolytic peroxidases. In the present
study, the GLOX-encoding gene (glx) of Phanerochaete chrysosporium was cloned,
and bee2 promoter of P. sordida YK-624 was used to drive the expression of glx.
The expression plasmid was transformed into a P. sordida YK-624 uracil
auxotrophic mutant (strain UV-64), and 16 clones were obtained as GLOX
introducing transformants. These transformants showed higher GLOX activities than
wild-type P. sordida YK-624 and control transformants harboring marker plasmid.
RT-PCR analysis indicated that the increased GLOX activity was associated with
elevated recombinant glx expression. Moreover, these transformants showed higher
ligninolytic activity than control transformants. These results suggest that the
ligninolytic properties of white-rot fungi can be improved by recombinant
expression of glx.
PMID- 25117934
TI - Molecular sensing using armchair graphene nanoribbon.
AB - In molecular electronics, the conductance strongly depends on the frontier energy
levels and spatial orientations of molecules. Utilizing these features, we
investigate the electron transport characteristics of conjugated molecules
attached on an armchair graphene nanoribbon. The resulting sharp reduction in the
transmission which represents molecular fingerprints and the change of the
transmission depending on the molecular orientation, are examined in accordance
with a unified picture of the Fano-Anderson model. These characteristics, being
unique for each molecule, would be applicable to molecular recognition and
configurational analysis.
PMID- 25117929
TI - Changes in proteinuria and albuminuria with initiation of antiretroviral therapy:
data from a randomized trial comparing tenofovir disoproxil
fumarate/emtricitabine versus abacavir/lamivudine.
AB - BACKGROUND: Antiretroviral therapy (ART) is associated with improved kidney
function; however, the nucleotide reverse transcriptase inhibitor (NRTI)
tenofovir disoproxil fumarate (TDF) has been associated with decreased kidney
function and proteinuria. METHODS: We examined changes in urine
protein:creatinine (UPCR) and urine albumin:creatinine (UACR) ratios in 245 ART
naive participants in A5202 randomized in a substudy to blinded NRTI
(abacavir/lamivudine, ABC/3TC, n = 124 or TDF/emtricitabine, TDF/FTC, n = 121)
with open-label protease inhibitor (PI) atazanavir/ritonavir or nonnucleoside
reverse transcriptase inhibitor (NNRTI) efavirenz. RESULTS: At baseline, 18% of
participants had clinically significant proteinuria (UPCR >=200 mg/g), and 11%
had clinically significant albuminuria (UACR >=30 mg/g). The prevalence of
clinically significant proteinuria and albuminuria decreased from baseline to
week 96 in all treatment groups. In intention-to-treat analyses, there was a
significant effect of NRTI component on fold change in UPCR (P = 0.011) and UACR
(P = 0.018) from baseline to week 96, with greater improvements in participants
randomized to ABC/3TC. There was no significant effect of NNRTI/PI component on
fold change in UPCR (P = 0.23) or UACR (P = 0.88), and no significant
interactions between NRTI and NNRTI/PI components. CONCLUSIONS: In this
prespecified secondary analysis, ART initiation was associated with improvements
in proteinuria and albuminuria, with significantly greater improvements in
participants randomized to ABC/3TC versus TDF/FTC. These are the first data from
a randomized trial to suggest that initiation of TDF/FTC may not be associated
with the same degree of improvement in proteinuria and albuminuria that have been
reported with other regimens. Future studies should consider the long-term
clinical significance of these findings.
PMID- 25117931
TI - Self-assembly and release of peste des petits ruminants virus-like particles in
an insect cell-baculovirus system and their immunogenicity in mice and goats.
AB - Peste des petits ruminants (PPR) is an acute, febrile, viral disease of small
ruminants that has a significant economic impact. For many viral diseases,
vaccination with virus-like particles (VLPs) has shown considerable promise as a
prophylactic approach; however, the processes of assembly and release of peste
des petits ruminants virus (PPRV) VLPs are not well characterized, and their
immunogenicity in the host is unknown. In this study, VLPs of PPRV were generated
in a baculovirus system through simultaneous expression of PPRV matrix (M)
protein and hemaglutin in (H) or fusion (F) protein. The released VLPs showed
morphology similar to that of the native virus particles. Subcutaneous injection
of these VLPs (PPRV-H, PPRV-F) into mice and goats elicited PPRV-specific IgG
production, increased the levels of virus neutralizing antibodies, and promoted
lymphocyte proliferation. Without adjuvants, the immune response induced by the
PPRV-H VLPs was comparable to that obtained using equivalent amounts of PPRV
vaccine. Thus, our results demonstrated that VLPs containing PPRV M protein and H
or F protein are potential "differentiating infected from vaccinated animals"
(DIVA) vaccine candidates for the surveillance and eradication of PPR.
PMID- 25117932
TI - Rab11 regulates E-cadherin expression and induces cell transformation in
colorectal carcinoma.
AB - BACKGROUND: In the process of epithelial mesenchymal transition EMT, the
disassembly of junctional adhesion complexes such as E-cadherin is a remarkable
sign during changes in cell morphology and polarity. However, E-cadherin
expression is dynamic, and is regulated by the cellular endocytic system; it is
also involved in cell signaling mechanisms. In this study, we investigated the
role of E-cadherin in colorectal tumors and the relationship with recycling
endosome protein Rab11 in colon cell transformation. METHODS: For tissue
screening, the expressions of E-cadherin and Rab11 in colorectal tumors were
identified by immunohistochemistry in 113 patients with colorectal carcinoma. For
the in vitro cell experiment, GFP-tagged Rab11 plasmid was transfected into HT29
colon cells, E-cadherin expression and cell transformation were monitored by
Western blot and confocal microscopy. RESULTS: In immunohistochemistry, the mean
score of E-cadherin in tumor and normal tissues was 1.41 +/- 0.06 and 1.08 +/-
0.06 (p < 0.05). The mean score of Rab11 in tumor and normal tissues was 0.51 +/-
0.05 and 0.18 +/- 0.02 (p < 0.05). Synchronous overexpression of E-cadherin and
Rab11 was noted in 74 patients (66.5%) with colorectal carcinoma. When GFP-tagged
Rab11 plasmid was overexpressed in cultured colon cell line HT-29, the E-cadherin
expression was up-regulated, and cell membrane protrusion was induced, which
resulted in cell transformation and cell migration. CONCLUSIONS: This study
demonstrated the importance of the overexpression of Rab11 and E-cadherin in
colorectal cancer. The results indicated that Rab11 together with E-cadherin
might be potential markers for colorectal cancer progression and treatment.
PMID- 25117935
TI - Comparison of root transcriptomes and expressions of genes involved in main
medicinal secondary metabolites from Bupleurum chinense and Bupleurum
scorzonerifolium, the two Chinese official Radix bupleuri source species.
AB - Radix bupleuri, roots of Bupleurum species, is a widely used traditional Chinese
medicine. Here, we compared the root transcriptomes of both Bupleurum chinense
DC. and Bupleurum scorzonerifolium Willd. A total of 313 483 and 342 263 high
quality expressed sequence tags were obtained, respectively. In addition, 17 117
(59.2%) and 19 416 (62.8%) unigenes for B. chinense and B. scorzonerifolium had
homologous genes in the opposite dataset. For B. chinense, Kyoto Encyclopedia of
Genes and Genomes database (KEGG) annotation identified carbohydrate metabolism,
energy metabolism and amino acid metabolism as the three highest groups in the
metabolism category. For B. scorzonerifolium, the lipid metabolism group had the
most unigenes. Genes that may participate in the biosynthesis of terpenoid,
triterpenoid, sterol, lignan and flavonoids were identified according to their
annotations. (Tri)terpenoid-related genes were predominantly found in B.
chinense. The expressions of certain genes were analyzed by quantitative reverse
transcription-polymerase chain reaction (qRT-PCR) in the roots of the two
species. A total of 558 putative transcription factors (TFs) and 137
transcriptional regulators (TRs) among 1364 TFs and 327 TRs, and 610 TFs and 129
TRs among 1600 TFs and 323 TRs were specific for B. chinense and B.
scorzonerifolium, respectively. Our transcriptome comparison reflects the
different types and proportions of metabolites synthesized by the two species.
The data, especially, those genes involved in the biosynthesis of particular
types of metabolites, will provide the basis for further investigations of the
secondary metabolite repertoire of the two Bupleurum species, as well as other
species from the genus of Bupleurum.
PMID- 25117937
TI - Moderate temperature increase leads to disintegration of floating sludge and
lower abundance of the filamentous bacterium Microthrix parvicella in anaerobic
digesters.
AB - Filamentous bacteria such as Microthrix parvicella can cause serious foaming and
floating sludge problems in anaerobic digesters fed with sewage sludge. The
sewage sludge and oil co-fermenting laboratory-scale biogas digesters in this
study were fed with substrates from a foaming-prone full-scale biogas plant
containing the filamentous bacterium M. parvicella. At 37 degrees C, in both
pneumatically mixed digesters a highly viscous and approximately 3 cm thick
floating sludge was observed. A gradual increase of the temperature from 37
degrees C to 56 degrees C led to a significant decrease in the floating sludge
thickness, which correlated with a strong decrease in the abundance of M.
parvicella in the digestate. Furthermore, the stepwise temperature increase
allowed for an adaption of the microbial community and prevented process failure.
The study indicates that already a moderate temperature increase from 37 degrees
C to 41 degrees C might help to control the M. parvicella abundance in full
scale biogas plants.
PMID- 25117938
TI - When will the TBT go away? Integrating monitoring and modelling to address TBT's
delayed disappearance in the Drammensfjord, Norway.
AB - Despite a substantial decrease in the use and production of the marine
antifouling agent tributyltin (TBT), its continuing presence in harbors remains a
serious environmental concern. Herein a case study of TBT's persistence in the
Drammensfjord, Norway, is presented. In 2005, severe TBT pollution was measured
in the harbor of the Drammensfjord, with an average sediment concentration of
3387 MUg kg(-1). To chart natural recovery in the Drammensfjord, an extensive
sampling campaign was carried out over six years (2008-2013), quantifying TBT in
water, settling particles and sediments. The monitoring campaign found a rapid
decrease in sediment TBT concentration in the most contaminated areas, as well as
a decrease in TBT entering the harbor via rivers and urban runoff. Changes
observed in the more remote areas of the Drammensfjord, however, were less
substantial. These data, along with measured and estimated geophysical
properties, were used to parameterize and calibrate a coupled linear water
sediment model, referred to as the Drammensfjord model, to make prognosis on
future TBT levels due to natural recovery. Unique to this type of model, the
calibration was done using a Bayesian Monte Carlo (BMC) updating approach, which
used monitoring data to calibrate predictions, as well as reduce the uncertainty
of input parameters. To our knowledge, this is the first use of BMC updating to
calibrate a model describing natural recovery in a lake/harbor type system. Prior
to BMC updating, the non-calibrated model data agreed with monitoring data by a
factor of 4.3. After BMC updating, the agreement was within a factor 3.2. The non
calibrated model predicted an average sediment concentration in the year 2025 of
2.5 MUg kg(-1). The BMC calibrated model, however, predicted a higher
concentration in the year 2025 of 16 MUg kg(-1). This discrepancy was mainly due
to the BMC calibration increasing the estimated riverine and runoff TBT emission
levels relative to the initial input levels. Future monitoring campaigns can be
used for further calibration of emission levels, and a clearer prognosis of when
natural recovery will remove TBT pollution.
PMID- 25117936
TI - Utilization of a novel digital measurement tool for quantitative assessment of
upper extremity motor dexterity: a controlled pilot study.
AB - BACKGROUND: The current methods of assessing motor function rely primarily on the
clinician's judgment of the patient's physical examination and the patient's self
administered surveys. Recently, computerized handgrip tools have been designed as
an objective method to quantify upper-extremity motor function. This pilot study
explores the use of the MediSens handgrip as a potential clinical tool for
objectively assessing the motor function of the hand. METHODS: Eleven patients
with cervical spondylotic myelopathy (CSM) were followed for three months.
Eighteen age-matched healthy participants were followed for two months. The
neuromotor function and the patient-perceived motor function of these patients
were assessed with the MediSens device and the Oswestry Disability Index
respectively. The MediSens device utilized a target tracking test to investigate
the neuromotor capacity of the participants. The mean absolute error (MAE)
between the target curve and the curve tracing achieved by the participants was
used as the assessment metric. The patients' adjusted MediSens MAE scores were
then compared to the controls. The CSM patients were further classified as either
"functional" or "nonfunctional" in order to validate the system's responsiveness.
Finally, the correlation between the MediSens MAE score and the ODI score was
investigated. RESULTS: The control participants had lower MediSens MAE scores of
8.09%+/-1.60%, while the cervical spinal disorder patients had greater MediSens
MAE scores of 11.24%+/-6.29%. Following surgery, the functional CSM patients had
an average MediSens MAE score of 7.13%+/-1.60%, while the nonfunctional CSM
patients had an average score of 12.41%+/-6.32%. The MediSens MAE and the ODI
scores showed a statistically significant correlation (r=-0.341, p<1.14*10-5). A
Bland-Altman plot was then used to validate the agreement between the two scores.
Furthermore, the percentage improvement of the the two scores after receiving the
surgical intervention showed a significant correlation (r=-0.723, p<0.04).
CONCLUSIONS: The MediSens handgrip device is capable of identifying patients with
impaired motor function of the hand. The MediSens handgrip scores correlate with
the ODI scores and may serve as an objective alternative for assessing motor
function of the hand.
PMID- 25117939
TI - The Comparison of Food and Supplement as Probiotic Delivery Vehicles.
AB - Probiotics are live bacteria which have frequently been reported to be beneficial
in preventing a wide range of diseases as well as playing a major role in
treating the existing ailments. Thus far, a variety of probiotic products have
been developed which can be categorized into two groups: probiotic foods and
supplements. Both foods and supplements have been able to confer the health
benefits claimed for them. However, it is not known which one can be clinically
more efficient, and to the best of our knowledge, until now no research has been
conducted to investigate this issue. The present review aims to discuss this
matter, based on the evidence available in the literature. To do so, articles
indexed in PubMed and ScienceDirect between 2000 and 2011 were reviewed. The
articles included the clinical trials in which either foods or supplements were
used to administer the probiotics to either patients suffering from different
diseases or healthy subjects. Although both foods and supplements seem to have
been efficient carriers for the beneficial bacteria, to generally promote public
health in communities, probiotic foods appear to be preferred to probiotic
supplements.
PMID- 25117940
TI - Deficits in auditory frequency discrimination and speech recognition in cochlear
implant users.
AB - OBJECTIVES: Speech recognition varies considerably following cochlear
implantation for reasons that are still poorly understood. Considering the role
of frequency discrimination in normal speech recognition, the aim of this study
was to investigate the association between deficits in auditory frequency
discrimination and speech recognition in cochlear implant users. METHODS:
Frequency discrimination thresholds and speech recognition were assessed in a
group of 20 cochlear implant users and 16 normally hearing controls. RESULTS:
Based on their results on the speech recognition task, the cochlear implant users
were categorized either as proficient (n = 10) or non-proficient users (n = 10).
The non-proficient cochlear implant users had poorer auditory frequency
discrimination compared to the normal hearing participants and proficient
cochlear implant users (both P < 0.05). No significant difference was found
between the proficient cochlear implant users and the normally hearing group (P >
0.05). Furthermore, a bivariate correlation analysis revealed a relationship
between speech recognition and frequency discrimination. CONCLUSIONS: The present
findings suggest an association between auditory frequency discrimination and
speech recognition proficiency in cochlear implant users. Although no causal link
can be drawn from these data, possible reasons for this association are
discussed.
PMID- 25117941
TI - Experimental amine-epoxide sealer: a physicochemical study in comparison with AH
Plus and EasySeal.
AB - AIM: To compare selected physicochemical and biological properties of an
experimental sealer with those of two commercially available sealers.
METHODOLOGY: AH Plus and EasySeal were used as model materials for commercially
available amine-epoxide sealers. They were mixed as stated by the manufacturer.
The two components of experimental sealer EvoSeal A were mixed 1 : 1 vol%. The
setting time was determined in two different ways: first, by setting of sealers
in a temperature- and moisture-controlled environment followed by testing with a
Gilmore needle and secondly, by oscillating measurements of setting behaviour
using a rheometer. Differential scanning calorimetry (DSC) of the sealer was
performed for comparison of thermal properties. Flow and film thickness were
determined by applying pressures of 100 g and 15.3 kg, respectively, on the
materials between two glass plates and measuring the diameters of the compressed
sealer and the thickness with a micrometer gauge. Solubility of set materials was
conducted by layering the samples with water, storing in a temperature- and
humidity-controlled environment and evaporating the solvent. The solved sealer
parts were then weighed. The radiopacity was measured in an X-ray experiment
comparing radiopacity of a cured sealer to an aluminium step wedge. Volume
shrinkage was defined by measuring the densities of samples before and after
setting. The film thickness, fluidity, curing time, radiopacity and solubility of
the test materials were performed as specified in DIN EN ISO 6876:2010 draft. The
volume shrinkage was determined in a method adapted from standard DIN 13907:2007
01. Antibacterial activity was tested against Gram-positive Streptococcus oralis
cultures in a contact test based on standard ISO 22196:2011 (E). Statistical
analysis was performed using Mann-Whitney U-test where applicable. Significant
differences were determined with P < 0.05. RESULTS: The experimental sealer,
EvoSeal A, reached standard specifications. In terms of film thickness, the
highest value was measured for EvoSeal A with a film thickness of 27 MUm,
comparing to 6 MUm for EasySeal (P <= 0.001) and 8 MUm for AH Plus (P <= 0.001).
Comparing the flow, all values corresponded to EasySeal with a diameter of 17.3
mm. The only significant difference was determined for AH Plus compared to
EvoSeal A (P = 0.0353). Volume shrinkage of EvoSeal A was 48% smaller compared to
EasySeal and approximately 20% lower compared to AH Plus. The shortest curing
time was determined for EvoSeal A (3.0 h) followed by EasySeal (4.1 h) and AH
Plus (24 h). For all groups, significant differences were observed (P <= 0.001).
EvoSeal A had a significantly higher radiopacity than EasySeal (P <= 0.001) but
significantly lower values than AH Plus (P <= 0.001). The solubility of AH Plus
and EvoSeal A was <0.5% (P = 0.2435). Compared to EasySeal with a solubility of
2.7%, significant differences were observed (P <= 0.02). Three weeks after
setting, EasySeal and EvoSeal A still had an antibacterial effect against S.
oralis in contrast to AH Plus. In this respect, comparing AH Plus with EvoSeal A
and EasySeal, respectively, significant differences were observed (P <= 0.001).
No significant differences between EasySeal with EvoSeal A (P = 0.540) were
determined. CONCLUSIONS: The physical and chemical properties of the experimental
sealer EvoSeal A were comparable to the two commercially established sealers
EasySeal and AH Plus.
PMID- 25117942
TI - Barriers to physical activity in chronic hemodialysis patients: a single-center
pilot study in an Italian dialysis facility.
AB - BACKGROUND/AIMS: In patients on chronic dialysis a sedentary lifestyle is a
strong, yet potentially modifiable, predictor of mortality. The present single
center pilot study evaluated social, psychological and clinical barriers that may
hinder physical activity in this population. METHODS: We explored the association
between barriers to physical activity and sedentarism in adult patients at a
chronic dialysis facility in Parma, Italy. We used different questionnaries
exploring participation in physical activity, physical functioning, patient
attitudes and preferences, and barriers to physical activity perceived by either
patients or dialysis doctors and nurses. RESULTS: We enrolled 104 patients, (67
males, 65%), mean age 69 years (79% of patients older than 60 years); median
dialysis vintage 60 months (range 8-440); mean Charlson score 5.55, ADL
(Activities of Daily Living) score 5.5. Ninety-two participants (88.5%) reported
at least one barrier to physical activity. At multivariable analysis, after
adjusting for age and sex, feeling to have too many medical problems (OR 2.99,
95% CI 1.27 to 7.07; P=0.012), chest pain (OR 10.78, 95% CI 1.28 to 90.28;
P=0.029) and sadness (OR 2.59, 95% CI 1.10 to 6.09; P=0.030) were independently
associated with physical inactivity. Lack of time for exercise counseling and the
firm belief about low compliance/interest by the patients toward exercise were
the most frequent barriers reported by doctors and nurses. CONCLUSION: We
identified a number of patient-related and health personnel-related barriers to
physical activity in patients on chronic dialysis. Solutions for these barriers
should be addressed in future studies aimed at increasing the level of physical
activity in this population.
PMID- 25117943
TI - Airway pH monitoring in patients with suspected obstructive sleep apnoea using
the Dx-pH oropharyngeal probe: preliminary report of a prospective cohort study.
AB - OBJECTIVES: To investigate the laryngopharyngeal reflux (LPR) episodes and pH
values in patients with suspected obstructive sleep apnoea (OSA) using the Dx-pH
oropharyngeal probe. DESIGN: Prospective cohort study. SETTING: Tertiary medical
centre. PARTICIPANTS: Forty patients with complaint of snoring or suspected OSA
were prospectively enrolled to receive full nocturnal polysomnography (PSG). The
patients were divided into 2 groups: a simple snorers group if the Respiratory
Disturbance Index (RDI) was < 5 and an OSA group if the RDI was >= 5. MAIN
OUTCOME MEASURES: The patients simultaneously received Dx-pH oropharyngeal probe
monitoring for 12 h from about 6 pm to 6 am of the next day. The number of LPR
events was recorded if the nadir of rapid pH drops was below pH 5.0 and 5.5. The
difference of LPR events between the two groups and the difference of LPR events
between awake and sleep periods in each group were analysed, respectively.
RESULTS: There were 18 (45%) patients diagnosed as OSA with a mean RDI of 28.7,
and 22 patients (55%) diagnosed as simple snorers. Between 2 groups, there were
no significant differences in the LPR events and pH values during the awake
period, sleep period or overall recording period. Comparison of the LPR events
and minimum pH values between the awake period and the sleep period revealed
there were no significant differences in either group. CONCLUSION: Using the new
sensitive Dx-pH oropharyngeal probe with PSG, we found that OSA does not
correlate with a higher incidence of LPR episodes.
PMID- 25117949
TI - Comparative investigation of in vitro biotransformation of 14 components in
Ginkgo biloba extract in normal, diabetes and diabetic nephropathy rat intestinal
bacteria matrix.
AB - Most herbal medicines will be metabolized by intestinal bacteria in the
gastrointestinal tract before absorbed by the small intestine. Ginkgo biloba
extract (GBE) possesses protective effects on the glomerulosclerosis of diabetic
nephropathy (DN), but its biotransformation in diabetes and DN intestinal
bacteria has not yet been recognized. In this work, a validated liquid
chromatography-tandem mass spectrometry (LC-MS) method was established for the
simultaneous quantification of 14 components in GBE in rat intestinal bacteria
matrix, namely ginkgolides A, ginkgolides B, ginkgolides C, bilobalide, rutin,
myricetin, quercitrin, quercetin, luteolin, genistein, kaempferol, apigenin,
isorhamnetin and genkwanin. Chromatographic separation was performed on a
Kromasil-C18 (4.6mm*250mm i.d., 5.0MUm) analytical column maintained at 35
degrees C. The mobile phase was a mixture of methanol (A) and 0.1% formic acid in
water (B) with a step linear gradient at a flow rate of 1.0mlmin(-1). The
calibration curves of these 14 analytes demonstrated good linearity within the
test range (R>0.99). This validated method has successfully been applied into the
pharmacokinetic study of the 14 components. More importantly, in the
pharmacokinetic study, by comparing the time course of the biotransformation by
normal, diabetes and DN rat intestinal bacteria, we found that the
biotransformation speed and residence time of the 14 compounds in diabetes and DN
rats differed obviously from that obtained in normal group, which provided
valuable chemical information for further pharmacology and active mechanism
research on GBE.
PMID- 25117950
TI - Development of a stability-indicating HPLC method of etifoxine with
characterization of degradation products by LC-MS/TOF, 1H and 13C NMR.
AB - This paper describes a new LC-MS/TOF method for the degradation products
determination when Etifoxine (ETI) is submitted to different stress conditions.
Chromatography is performed by using Kromasil C18 column (250mm*4.6mm, 5MUm
particle size). The selected mobile phase consists of formate buffer 0.02M, pH 3
and methanol (70/30, v/v). ETI is submitted to oxidative, acidic, basic,
hydrolytic, thermal and UV light degradations. Detection is made at 254nm by
photodiode array detector and mass spectrometry. A number of degradation products
(DPs) called DPA, DPB, DPC and DPD are found depending on the stress; DPA with
heat, DPA and DPB in acidic media or under UV-light; DPA, DPB and DPC under basic
stress; DPA, DPB, DPC and DPD with oxidation. LC-MS/TOF is used to characterize
the four DPs of ETI resulting from different stress conditions. (1)H and (13)C
NMR are used to confirm the DP structures. The ETI fragmentation pathway is
proposed. The method is validated with reference to International Conference on
Harmonization guidelines and ETI are selectively determined in presence of its
DPs, demonstrating its stability-indicating nature. Finally, for the validation
step, specificity, linearity, accuracy and precision are determined for ETI and
its DPs.
PMID- 25117951
TI - Nanomechanical properties of poly(lactic-co-glycolic) acid film during
degradation.
AB - Despite the potential applications of poly(lactic-co-glycolic) acid (PLGA)
coatings in medical devices, the mechanical properties of this material during
degradation are poorly understood. In the present work, the nanomechanical
properties and degradation of PLGA film were investigated. Hydrolysis of solvent
cast PLGA film was studied in buffer solution at 37 degrees C. The mass loss,
water uptake, molecular weight, crystallinity and surface morphology of the film
were tracked during degradation over 20 days. Characterization of the surface
hardness and Young's modulus was performed using the nanoindentation technique
for different indentation loads. The initially amorphous films were found to
remain amorphous during degradation. The molecular weight of the film decreased
quickly during the initial days of degradation. Diffusion of water into the film
resulted in a reduction in surface hardness during the first few days, followed
by an increase that was due to the surface roughness. There was a significant
delay between the decrease in the mechanical properties of the film and the
decrease in the molecular weight. A sudden decline in mechanical properties
indicated that significant bulk degradation had occurred.
PMID- 25117953
TI - New series of avenanthramides in oat seed.
AB - Avenanthramides are characteristic constituents of oat seeds. We analyzed the
methanol extract of oat seeds by HPLC and detected three compounds 1, 2, and 3
eluted at retention times similar to avenanthramides. The three compounds were
purified by column chromatography and HPLC. Spectroscopic analyses of 1, 2, and 3
suggested that they are amides of 4,5-dihydroxyanthranilic acid with caffeic, p
coumaric, and ferulic acids, respectively. Their identities were confirmed by
comparing spectra and chromatographic behavior with compounds synthesized from
4,5-dihydroxyanthranilic acid and N-hyrdroxysuccinimide esters of hydroxycinnamic
acids. LC-MS/MS analysis with multiple reaction monitoring showed that the
amounts of 1, 2, and 3 were 16.5-26.9% of corresponding avenanthamides with 5
hydroxyanthranilic acid. Compounds 1, 2, and 3 showed stronger 2,2-diphenyl-1
picrylhydrazyl (DPPH) radical-scavenging activity than the corresponding
avenanthramides with 5-hydroxyanthranilic acid, indicating the involvement of 4,5
dihydroxyanthranilic acid moiety in the scavenging of DPPH radicals.
PMID- 25117954
TI - Illuminating the origins of spectral properties of green fluorescent proteins via
proteochemometric and molecular modeling.
AB - Green fluorescent protein (GFP) has immense utility in biomedical imaging owing
to its autofluorescent nature. In efforts to broaden the spectral diversity of
GFP, there have been several reports of engineered mutants via rational design
and random mutagenesis. Understanding the origins of spectral properties of GFP
could be achieved by means of investigating its structure-activity relationship.
The first quantitative structure-property relationship study for modeling the
spectral properties, particularly the excitation and emission maximas, of GFP was
previously proposed by us some years ago in which quantum chemical descriptors
were used for model development. However, such simplified model does not consider
possible effects that neighboring amino acids have on the conjugated pi-system of
GFP chromophore. This study describes the development of a unified
proteochemometric model in which the GFP chromophore and amino acids in its
vicinity are both considered in the same model. The predictive performance of the
model was verified by internal and external validation as well as Y-scrambling.
Our strategy provides a general solution for elucidating the contribution that
specific ligand and protein descriptors have on the investigated spectral
property, which may be useful in engineering novel GFP variants with desired
characteristics.
PMID- 25117952
TI - Antibody-functionalized peptidic membranes for neutralization of allogeneic skin
antigen-presenting cells.
AB - We report herein application of an in situ material strategy to attenuate
allograft T cell responses in a skin transplant mouse model. Functionalized
peptidic membranes were used to impede trafficking of donor antigen-presenting
cells (dAPCs) from skin allografts in recipient mice. Membranes formed by self
assembling peptides (SAPs) presenting antibodies were found to remain underneath
grafted skins for up to 6 days. At the host-graft interface, dAPCs were targeted
by using a monoclonal antibody that binds to a class II major histocompatibility
complex (MHC) molecule (I-A(d)) expressed exclusively by donor cells. Using a
novel cell labeling near-infrared nanoemulsion, we found more dAPCs remained in
allografts treated with membranes loaded with anti-I-A(d) antibodies than
without. In vitro, dAPCs released from skin explants were found adsorbed
preferentially on anti-I-A(d) antibody-loaded membranes. Recipient T cells from
these mice produced lower concentrations of interferon-gamma cultured ex vivo
with donor cells. Taken together, the data indicate that the strategy has the
potential to alter the natural course of rejection immune mechanisms in
allogeneic transplant models.
PMID- 25117955
TI - Macular hole secondary to Valsalva retinopathy after doing push-up exercise.
AB - BACKGROUND: Valsalva retinopathy and traumatic macular hole are common
conditions, but macular hole secondary to Valsalva retinopathy is rarely
reported. CASE PRESENTATION: A 34-year-old healthy man suffered Valsalva
retinopathy after doing push-up exercise. During his follow-up visits, the best
corrected visual acuity (BCVA) measurements, fundus examinations and spectral
domain optical coherence tomography (SD-OCT) tests were performed. Three months
later, the premacular hemorrhage was noticeably absorbed with an improvement of
visual acuity. SD-OCT showed a lamellar macular hole with intact but thickened
internal limiting membrane (ILM) with vitreal tractions on surface of the
macular. Nine months after the first visit, his vision acuity was 20/25. The
fundus examination showed a complete absorption of the macular hemorrhage. SD-OCT
showed that the lamellar macular hole has enlarged, with thickened ILM on the
surface. Seventeen months after the onset, the BCVA, fundus examination results
and OCT findings were stable. CONCLUSIONS: Macular hole secondary to Valsalva
retinopathy had been rarely reported and its mechanism needs further
understanding. SD-OCT can be used to observe the evolvement of Valsalva
retinopathy.
PMID- 25117956
TI - HIV/AIDS and noncommunicable disease comorbidities: emerging research priorities.
PMID- 25117958
TI - HIV and noncommunicable disease comorbidities in the era of antiretroviral
therapy: a vital agenda for research in low- and middle-income country settings.
AB - In this special 2014 issue of JAIDS, international investigator teams review a
host of noncommunicable diseases (NCDs) that are often reported among people
living and aging with HIV in sub-Saharan Africa. With the longer lifespans that
antiretroviral therapy programs have made possible, NCDs are occurring due to a
mix of chronic immune activation, medication side effects, coinfections, and the
aging process itself. Cancer; cardiovascular and pulmonary diseases; metabolic,
body, and bone disorders; gastrointestinal, hepatic, and nutritional aspects;
mental, neurological, and substance use disorders; and renal and genitourinary
diseases are discussed. Cost-effectiveness, key research methods, and issues of
special importance in Asia, Latin America, and the Caribbean are also addressed.
In this introduction, we present some of the challenges and opportunities for
addressing HIV and NCD comorbidities in low- and middle-income countries, and
preview the research agenda that emerges from the articles that follow.
PMID- 25117959
TI - HIV and metabolic, body, and bone disorders: what we know from low- and middle
income countries.
AB - Globally, the HIV epidemic is evolving. Life expectancy for HIV-infected
individuals has been extended because of more effective and more widely available
antiretroviral therapy. As a result, chronic noncommunicable diseases (NCDs) have
become important comorbid conditions. In particular, HIV-infected persons are
increasingly at risk of developing metabolic (diabetes, dyslipidemias), body
composition (lipodystrophy, overweight/obesity) and bone mineral density
abnormalities. We have summarized the published epidemiological and clinical
literature regarding these HIV-NCD comorbidities in low- and middle-income
countries (LMICs). We found important gaps in knowledge. Specifically, there are
few studies that use standardized methods and metrics; consequently, prevalence
or incidence data are not comparable. There are very little or no data regarding
the effectiveness or cost-effectiveness of clinical monitoring or therapeutic
interventions for metabolic disorders in HIV-infected individuals. Also, although
NCDs continue to grow in the HIV-negative population of most LMICs, there are few
data comparing the incidence of NCD comorbidities between HIV-infected and HIV
negative populations. To address these gaps, we describe potential research and
capacity development priorities for the future.
PMID- 25117957
TI - Challenges in the detection, prevention, and treatment of HIV-associated
malignancies in low- and middle-income countries in Africa.
AB - Cancers associated with immunosuppression and infections have long been
recognized as a major complication of HIV/AIDS. More recently, persons living
with HIV are increasingly diagnosed with a wider spectrum of HIV-associated
malignancies (HIVAM) as they live longer on combination antiretroviral therapy.
This has spurred research to characterize the epidemiology and determine the
optimal management of HIVAM with a focus on low-and middle-income countries
(LMICs). Given background coinfections, environmental exposures, host genetic
profiles, antiretroviral therapy usage, and varying capacities for early
diagnosis and treatment, one can expect the biology of cancers in HIV-infected
persons in LMICs to have a significant impact on chronic HIV care, as is now the
case in high-income countries. Thus, new strategies must be developed to
effectively prevent, diagnose, and treat HIVAM in LMICs; provide
physical/clinical infrastructures; train the cancer and HIV workforce; and expand
research capacity-particularly given the challenges posed by the limitations on
available transportation and financial resources and the population's general
rural concentration. Opportunities exist to extend resources supported by the
President's Emergency Plan for AIDS Relief and the Global Fund to Fight AIDS,
Tuberculosis, and Malaria to improve the health-care infrastructure and train the
personnel required to prevent and manage cancers in persons living with HIV.
These HIV chronic care infrastructures could also serve cancer patients
regardless of their HIV status, facilitating long-term care and treatment for
persons who do not live near cancer centers, so that they receive the same degree
of care as those receiving chronic HIV care today.
PMID- 25117961
TI - Mental, neurological, and substance use disorders in people living with HIV/AIDS
in low- and middle-income countries.
AB - Depression, alcohol use disorders (AUD), and neurocognitive disorders are the 3
most prevalent mental, neurological, and substance use disorders in people living
with HIV infection in low- and middle-income countries (LMICs). Importantly, they
have an impact on everyday functions and on HIV outcomes. Many LMICs have
validated tools to screen for and diagnose depression and AUD in the general
population that can be used among people living with HIV infection. Current
screening and diagnostic methods for HIV-associated neurocognitive disorders in
the era of antiretroviral therapy are suboptimal and require further research. In
our view, 2 research priorities are most critical. One is the development of an
integrated screening approach for depression, AUD, and neurocognitive disorders
that can be used by nonspecialists in LMICs. Second, research is needed on
interventions for depression and AUD that also target behavior change, as these
could impact on adherence to antiretroviral therapy and improve mental symptoms.
Mentorship and fellowship schemes at an individual and institutional level need
to be further supported to build capacity and provide platforms for research on
HIV and mental, neurological, and substance use disorders in LMICs.
PMID- 25117962
TI - HIV-associated renal and genitourinary comorbidities in Africa.
AB - With the recent massive scale-up of access to antiretroviral therapy (ART) in
resource-limited countries, HIV has become a chronic disease with new challenges.
There is mounting evidence of an increased burden of renal and genitourinary
diseases among HIV-infected persons caused by direct HIV viral effects and/or
indirectly through the development of opportunistic infections, ART medication
related toxicities, and other noncommunicable diseases (NCDs). We review the
epidemiology of HIV-associated renal and urogenital diseases, including
interactions with kidney-related NCDs such as hypertension, diabetes mellitus,
and cardiovascular disease. We also examine the current evidence regarding the
impact of HIV infection on the development of urogenital diseases. Highly
advisable in sub-Saharan Africa are the establishment of renal disease
registries, reviews of existing clinical practice including cost-effectiveness
studies, and the adoption and use of HIV-related NCD management, with training
for different cadres of health providers. Epidemiological research priorities
include prospective studies to evaluate the true prevalence and spectrum of HIV
related renal disease and their progression. Simple diagnostics tools should be
evaluated, including urinary dipsticks and point-of-care urea and creatinine
tests to screen for kidney injury in primary care settings. Study of urological
manifestations of HIV can help determine the extent of disease and outcomes. As
patients live longer on ART, the burden of renal and genitourological
complications of HIV and of ART can be expected to increase with a commensurate
urgency in both discovery and evidence-based improvements in clinical management.
PMID- 25117960
TI - HIV and noncommunicable cardiovascular and pulmonary diseases in low- and middle
income countries in the ART era: what we know and best directions for future
research.
AB - With the advent of effective antiretroviral therapy (ART), HIV is becoming a
chronic disease. HIV-seropositive (+) patients on ART can expect to live longer
and, as a result, they are at risk of developing chronic noncommunicable diseases
related to factors, such as aging, lifestyle, long-term HIV infection, and the
potential adverse effects of ART. Although data are incomplete, evidence suggests
that even in low- and middle-income countries (LMICs), chronic cardiovascular and
pulmonary diseases are increasing in HIV-positive patients. This review
summarizes evidence-linking HIV infection to the most commonly cited chronic
cardiovascular and pulmonary conditions in LMICs: heart failure, hypertension,
coronary artery disease/myocardial infarction, stroke, obstructive lung diseases,
and pulmonary arterial hypertension. We describe the observed epidemiology of
these conditions, factors affecting expression in LMICs, and key populations that
may be at higher risk (ie, illicit drug users and children), and finally, we
suggest that strategic areas of research and training intended to counter these
conditions effectively. As access to ART in LMICs increases, long-term outcomes
among HIV-positive persons will increasingly be determined by a range of
associated chronic cardiovascular and pulmonary complications. Actions taken now
to identify those conditions that contribute to long-term morbidity and mortality
optimize early recognition and diagnosis and implement effective prevention
strategies and/or disease interventions are likely to have the greatest impact on
limiting cardiovascular and pulmonary disease comorbidity and improving
population health among HIV-positive patients in LMICs.
PMID- 25117966
TI - HIV and noncommunicable diseases (NCDs) in Latin America: a call for an
integrated and comprehensive response.
AB - The life expectancy of people living with HIV has dramatically improved with the
much increased access to antiretroviral therapy. Consequently, a larger number of
people living with HIV are living longer and facing the increased burden of
noncommunicable diseases (NCDs). NCDs and HIV infection share common
epidemiologic and sociodemographic characteristics that influence their outcomes,
which may be difficult to address in the relatively weak health systems of the
region. Data on the prevalence and interactions of NCDs and HIV in Latin American
countries remain very limited, which hinders their governments' ability to make
informed decisions about health care policies. Therefore, there is an urgent need
to develop a research agenda that will be the basis for an integrated and
comprehensive health care approach to HIV and NCD comorbidities in Latin America.
PMID- 25117964
TI - Observational research on NCDs in HIV-positive populations: conceptual and
methodological considerations.
AB - Noncommunicable diseases (NCDs) account for a growing burden of morbidity and
mortality among people living with HIV in low- and middle-income countries
(LMICs). HIV infection and antiretroviral therapy interact with NCD risk factors
in complex ways, and research into this "web of causation" has so far been
largely based on data from high-income countries. However, improving the
understanding, treatment, and prevention of NCDs in LMICs requires region
specific evidence. Priority research areas include: (1) defining the burden of
NCDs among people living with HIV, (2) understanding the impact of modifiable
risk factors, (3) evaluating effective and efficient care strategies at
individual and health systems levels, and (4) evaluating cost-effective
prevention strategies. Meeting these needs will require observational data, both
to inform the design of randomized trials and to replace trials that would be
unethical or infeasible. Focusing on Sub-Saharan Africa, we discuss data
resources currently available to inform this effort and consider key limitations
and methodological challenges. Existing data resources often lack population
based samples; HIV-negative, HIV-positive, and antiretroviral therapy-naive
comparison groups; and measurements of key NCD risk factors and outcomes. Other
challenges include loss to follow-up, competing risk of death, incomplete outcome
ascertainment and measurement of factors affecting clinical decision making, and
the need to control for (time-dependent) confounding. We review these challenges
and discuss strategies for overcoming them through augmented data collection and
appropriate analysis. We conclude with recommendations to improve the quality of
data and analyses available to inform the response to HIV and NCD comorbidity in
LMICs.
PMID- 25117963
TI - Noncommunicable diseases in HIV infection in low- and middle-income countries:
gastrointestinal, hepatic, and nutritional aspects.
AB - The purpose of this review was to outline the interaction between HIV and
noncommunicable diseases affecting the gastrointestinal (GI) tract, liver, and
nutritional disorders in low- and middle-income countries (LMICs), and to
identify research priorities. Noncommunicable GI tract disorders are only
moderately influenced by HIV, and peptic ulceration is actually less common.
However, the impact of HIV on GI cancers needs further investigation. HIV
interacts strongly with environmental enteropathy, exacerbating malabsorption of
nutrients and drugs. HIV has 2 major effects on noncommunicable liver disease:
drug-induced liver injury and nonalcoholic fatty liver disease (particularly in
persons of African genetic descent). The effect of HIV on nutrition was one of
the first markers of the epidemic in the 1980s, and HIV continues to have major
nutritional consequences. Childhood malnutrition and HIV frequently coexist in
some regions, for example, southern Africa, resulting in powerful negative
interactions with poorer responses to standard nutritional rehabilitation. HIV
and nutritional care need to be better integrated, but many questions on how best
to do this remain unanswered. Across the spectrum of GI, hepatic, and nutritional
disorders in HIV infection, there is increasing evidence that the microbiome may
play an important role in disease pathogenesis, but work in this area, especially
in low- and middle-income countries, is in its infancy.
PMID- 25117967
TI - HIV and noncommunicable diseases: the Asian perspective.
AB - Asia is seeing a rise in noncommunicable diseases in their general population and
among people living with HIV. Many Asians have low body weight, which can lead to
higher plasma concentrations of antiretrovirals and, as a result, their
toxicities. Examples are metabolic complications from protease inhibitors,
chronic kidney disease from tenofovir, and hepatotoxicity from nevirapine. Asia
has not only the highest burden of hepatitis B viral infection than any other
continent but also a predominance of genotypes B and C, the latter associated
with higher risk for hepatocellular carcinoma. HIV-associated neurocognitive
disorders are equally common among Asians as other populations. Diastolic
dysfunction and asymptomatic myocardial ischemia are not infrequent. Non-Hodgkin
lymphoma is the most common AIDS-related cancer, whereas Kaposi sarcoma is
relatively infrequent. Emerging data show high prevalence of human papillomavirus
associated anal dysplasia in men who have sex with men. Resource-limited
countries in Asia suffer from lack of resources for national screening programs
of noncommunicable diseases, which, in turn, limits the epidemiologic data that
exist to guide the use of national health resources.
PMID- 25117968
TI - Phylogenetic relationships and pathogenicity variation of two Newcastle disease
viruses isolated from domestic ducks in Southern China.
AB - BACKGROUND: Newcastle disease (ND) is an OIE listed disease caused by virulent
avian paramyxovirus type 1 (APMV-1) strains, which is enzootic and causes large
economic losses in the poultry sector. Genotype VII and genotype IX NDV viruses
were the predominant circulating genotype in China, which may possibly be
responsible for disease outbreaks in chicken flocks in recent years. While ducks
and geese usually have exhibited inapparent infections. METHODS: In the present
study, we investigate the complete genome sequence, the clinicopathological
characterization and transmission of two virulent Newcastle disease viruses, SS
10 and NH-10, isolated from domestic ducks in Southern China in 2010. RESULTS: F,
and the complete gene sequences based on phylogenetic analysis demonstrated that
SS-10 (genotype VII) and NH-10 (genotype IX) belongs to class II. The deduced
amino acid sequence was (112)R-R-Q-K/R-R-F(117) at the fusion protein cleavage
site. Animal experiment results showed that the SS-10 virus isolated from ducks
was highly pathogenic for chickens and geese, but low pathogenic for ducks. It
could be detected from spleen, lung, kidney, trachea, small intestine, bursa of
fabricius, thymus, pancreas and cecal tonsils, oropharyngeal and cloacal swabs,
and could transmit to the naive contact birds. Moreover, it could transmit to
chickens, ducks and geese by naive contact. However, the NH-10 virus isolated
from ducks could infect some chickens, ducks and geese, but only caused chickens
to die. Additionally, it could transmit to the naive contact chickens, ducks, and
geese. CONCLUSION: The two NDV isolates exhibited different biological properties
with respect to pathogenicity and transmission in chickens, ducks and geese.
Therefore, no species-preference exists for chicken, duck or goose viruses and
more attention should be paid to the trans-species transmission of VII NDVs
between ducks, geese and chickens for the control and eradication of ND.
PMID- 25117969
TI - Plerixafor is effective given either preemptively or as a rescue strategy in poor
stem cell mobilizing patients with multiple myeloma.
AB - BACKGROUND: Harvest of more than one CD34+ stem cell transplant has become the
standard, to ensure the option for a second autologous transplantation in
patients with relapsed or progressive multiple myeloma (MM). Additional
administration of the CXCR-4 inhibitor plerixafor has been shown to increase the
efficiency of CD34+ stem cell harvest. However, the algorithm when to apply
plerixafor is still under debate. STUDY DESIGN AND METHODS: In this retrospective
study, 46 MM patients were categorized into four groups according to their CD34+
stem cell count in peripheral blood (PB) and mobilization with or without
plerixafor: Group A comprised poor mobilizers with CD34+ cell counts of fewer
than 20 * 10(6) /L in PB. Group B included inadequate mobilizers with CD34+ cell
counts of 20 * 10(6) /L or more in PB and a low CD34+ stem cell yield in the
first leukapheresis session. Patients receiving plerixafor preemptively (Group
A1) and as a rescue strategy (Group B1) were compared to patients continuing stem
cell collection with granulocyte-colony-stimulating factor alone (Groups A2 and
B2). RESULTS: In both, the preemptive and the rescue settings, plerixafor
enhanced the CD34+ stem cell yield significantly. Poor mobilization and
administration of plerixafor was not associated with delayed engraftment.
CONCLUSION: Our data demonstrate that administration of plerixafor is safe and
effective and facilitates a significantly higher CD34+ stem cell harvest. Based
on the presented data, we propose an algorithm for the use of plerixafor for
CD34+ stem cell mobilization and harvesting in poor mobilizing myeloma patients.
PMID- 25117970
TI - Bacteriocins: Recent Trends and Potential Applications.
AB - In the modern era, there is great need for food preservation in both developing
and developed countries due to increasing demand for extending shelf life and
prevention of spoilage of food material. With the emergence of new pathogens and
ability of micro-organisms to undergo changes, exploration of new avenues for the
food preservation has gained importance. Moreover, awareness among consumers
regarding harmful effects of chemical preservatives has been increased. Globally,
altogether there is increasing demand by consumers for chemical-free and minimal
processed food products. Potential of bacteriocin and its application in reducing
the microbiological spoilages and in the preservation of food is long been
recognized. Bacteriocins are normally specific to closely related species without
disrupting the growth of other microbial populations. A number of applications of
bacteriocin have been reported for humans, live stock, aquaculture etc. This
review is focused on recent trends and applications of bacteriocins in different
areas in addition to their biopreservative potential.
PMID- 25117971
TI - Bacterial diversity in a contaminated Alpine glacier as determined by culture
based and molecular approaches.
AB - Glaciers are important ecosystems, hosting bacterial communities that are adapted
to cold conditions and scarcity of available nutrients. Several works focused on
the composition of bacterial communities in glaciers and on the long-range
atmospheric deposition of pollutants in glaciers, but it is not clear yet if ski
resorts can represent a source of point pollution in near-by glaciers, and if
these pollutants can influence the residing bacterial communities. To test these
hypotheses, 12 samples were analyzed in Madaccio Glacier, in a 3200 ma.s.l. from
two areas, one undisturbed and one close to a summer ski resort that is active
since the 1930s. Chemical analyses found concentrations up to 43 ng L(-1) for
PCBs and up to 168 MUg L(-1) for PAHs in the contaminated area: these values are
significantly higher than the ones found in undisturbed glaciers because of long
range atmospheric deposition events, and can be explained as being related to the
near-by ski resort activities. Isolation of strains on rich medium plates and PCR
DGGE analyses followed by sequencing of bands allowed the identification of a
bacterial community with phylogenetic patterns close to other glacier
environments, with Proteobacteria and Actinobacteria the mostly abundant phyla,
with Acidobacteria, Firmicutes and Cyanobacteria also represented in the culture
independent analyses. A number of isolates were identified by molecular and
biochemical methods as phylogenetic related to known xenobiotic-degrading
strains: glaciers subjected to chemical contamination can be important reservoirs
of bacterial strains with potential applications in bioremediation.
PMID- 25117973
TI - Comparison of eSRTs and comfort levels in users of Digisonic SP cochlear
implants.
AB - OBJECTIVE: This project proposes to assess the relation between the electrical
stapedius reflex threshold (eSRT) and comfort levels in users of the Digisonic SP
cochlear implant. METHODS: Cross-sectional study, where eSRTs are compared to the
comfort current levels at 2 weeks and at 1-year post-fitting in a group of 11
adults getting a significant improvement in open set speech recognition from a
Digisonic SP cochlear implant. RESULTS: The linear relation between eSRTs and
comfort levels results in Pearson correlation coefficients of 0.65 (P < 0.01; at
2 weeks) to 0.60 (P < 0.05; at 1 year). The comfort levels can be predicted from
the eSRTs for the Digisonic SP device from the model equation C level = 19.12 +
0.41*eSRT within a clinically acceptable margin of error. DISCUSSION: Reflex
thresholds could be obtained in most participants, and in most channels of the
Digisonic implant. The equation model appears as a quite reliable predictor of
comfort levels for users of this device.
PMID- 25117972
TI - Evaluation of bifidobacterial community composition in the human gut by means of
a targeted amplicon sequencing (ITS) protocol.
AB - The precise appraisal of the composition of the human gut microbiota still
represents a challenging task. The advent of next generation sequencing
approaches has opened new ways to dissect the microbial biodiversity of this
ecosystem through the use of 16S rRNA gene-based microbiota analysis approaches.
However, the detailed representation of specific groups or members of the human
gut microbiota, for example Bifidobacteria, may be skewed by the PCR primers
employed in the amplification step of the 16S rRNA gene-based microbial profiling
pipeline and by the limited resolution of the 16S rRNA gene variable regions.
Here, we define the internal transcribed spacer (ITS) sequences of all currently
known Bifidobacterium taxa, providing a Bifidobacterium-specific primer pair that
targets a hypervariable region within the ITS suitable for precise taxonomic
identification of all 48 so far recognized members of the Bifidobacterium genus.
In addition, we present an optimized protocol for ITS-based profiling utilizing
qiime software, allowing accurate and subspecies-specific compositional
reconstruction of the bifidobacterial community in the human gut.
PMID- 25117974
TI - Performance assessment of patient on dialysis.
AB - Patients on dialysis are poorly active and show a low level of physical
functioning. Questionnaires and objective measurements of spontaneous physical
activity are available as well as complex-expensive or simple-unexpensive tests
useful to assess the patient's exercise capacity. Performance assessment unravels
patients' capabilities, enables a tailored exercise prescription and provides
predictive information on main clinical outcomes and therefore this topic should
be of interest for nephrologists. A routinary minimal pool of tests might be
usefully performed in a dialysis centre to stratify the patient's risk and to
recognize patients in need of exercise training in order to address them to
community-based or rehabilitative programs.
PMID- 25117965
TI - HIV, tuberculosis, and noncommunicable diseases: what is known about the costs,
effects, and cost-effectiveness of integrated care?
AB - Unprecedented investments in health systems in low- and middle-income countries
(LMICs) have resulted in more than 8 million individuals on antiretroviral
therapy. Such individuals experience dramatically increased survival but are
increasingly at risk of developing common noncommunicable diseases (NCDs).
Integrating clinical care for HIV, other infectious diseases, and NCDs could make
health services more effective and provide greater value. Cost-effectiveness
analysis is a method to evaluate the clinical benefits and costs associated with
different health care interventions and offers guidance for prioritization of
investments and scale-up, especially as resources are increasingly constrained.
We first examine tuberculosis and HIV as 1 example of integrated care already
successfully implemented in several LMICs; we then review the published
literature regarding cervical cancer and depression as 2 examples of NCDs for
which integrating care with HIV services could offer excellent value. Direct
evidence of the benefits of integrated services generally remains scarce;
however, data suggest that improved effectiveness and reduced costs may be
attained by integrating additional services with existing HIV clinical care.
Further investigation into clinical outcomes and costs of care for NCDs among
people living with HIV in LMICs will help to prioritize specific health care
services by contributing to an understanding of the affordability and
implementation of an integrated approach.
PMID- 25117975
TI - A comparison between amylase levels from peritonsillar, dental and neck
abscesses.
AB - OBJECTIVES: Pus of peritonsillar abscess (PTA) contains very high amylase levels
in some patients. The objective of this study was to further test this finding
and to check whether high amylase levels in peritonsillar abscess originate from
contamination by saliva during aspiration. STUDY DESIGN: Prospective study.
SETTING: Tertiary care university hospital. PARTICIPANTS: The study includes 64
patients with PTA, 8 patients with a neck abscess and 12 patients with a dental
abscess. MAIN OUTCOME MEASURE: Amylase levels of pus and serum were compared
between the groups. Clinical data regarding hospitalisation length, recurrence
rate and previous antibiotic treatment were also collected. RESULTS: Mean amylase
levels in the pus of the PTA group were 3045 U/L (median 59 U/L), 13 U/L in the
neck abscess group (P = 0.001) and 22 U/L in the dental abscess group (P =
0.001). Mean serum amylase was higher in the PTA group; PTA - 50 U/L, neck
abscess - 37 U/L (P = 0.002) and dental abscess - 26 U/L (P < 0.002). All of the
patients with amylase levels above 65 U/L had a first episode of PTA. In
contrast, 40% of patients with amylase lower than 65 U/L had recurrent PTA (P =
0.003). CONCLUSION: A clear association is seen between minor salivary glands and
peritonsillar abscess. The high amylase level in peritonsillar pus is not from
contamination with saliva.
PMID- 25117976
TI - The major cow milk allergen Bos d 5 manipulates T-helper cells depending on its
load with siderophore-bound iron.
AB - The mechanisms of allergic sensitization to milk are still elusive. The major
allergen Bos d 5 belongs to the lipocalin-family and thus is able to transport
numerous ligands. In this study we investigated its ability to bind to iron
siderophore complexes and tested the immune-modulatory properties of Bos d 5 in
either forms. Structural and in silico docking analysis of Bos d 5 revealed that
Bos d 5 is able to bind to iron via catechol-based flavonoids (quercetin,
myricetin, luteolin) that act as siderophores as confirmed by spectral-analysis
and iron staining. Calculated dissociation constants of docking analyses were
below 1 uM by virtual addition of iron. When incubated with human peripheral
blood mononuclear cells (PBMCs), only the apo-form of Bos d 5 led to an increase
of CD4+positive cells and significantly elevated IL13 and IFNgamma-levels. In
contrast, holo-Bos d 5 decreased numbers of CD4 expressing cells and induced
apoptosis. Taken together, our data give evidence that Bos d 5 is capable of
binding iron via siderophores. Moreover, our data support for the first time the
notion that the form of application (apo- or holo-form) is decisive for the
subsequent immune response. The apo-form promotes Th2 cells and inflammation,
whereas the holo-form appears to be immunosuppressive.
PMID- 25117977
TI - Mechanisms of glioma formation: iterative perivascular glioma growth and invasion
leads to tumor progression, VEGF-independent vascularization, and resistance to
antiangiogenic therapy.
AB - As glioma cells infiltrate the brain they become associated with various
microanatomic brain structures such as blood vessels, white matter tracts, and
brain parenchyma. How these distinct invasion patterns coordinate tumor growth
and influence clinical outcomes remain poorly understood. We have investigated
how perivascular growth affects glioma growth patterning and response to
antiangiogenic therapy within the highly vascularized brain. Orthotopically
implanted rodent and human glioma cells are shown to commonly invade and
proliferate within brain perivascular space. This form of brain tumor growth and
invasion is also shown to characterize de novo generated endogenous mouse brain
tumors, biopsies of primary human glioblastoma (GBM), and peripheral cancer
metastasis to the human brain. Perivascularly invading brain tumors become
vascularized by normal brain microvessels as individual glioma cells use
perivascular space as a conduit for tumor invasion. Agent-based computational
modeling recapitulated biological perivascular glioma growth without the need for
neoangiogenesis. We tested the requirement for neoangiogenesis in perivascular
glioma by treating animals with angiogenesis inhibitors bevacizumab and DC101.
These inhibitors induced the expected vessel normalization, yet failed to reduce
tumor growth or improve survival of mice bearing orthotopic or endogenous gliomas
while exacerbating brain tumor invasion. Our results provide compelling
experimental evidence in support of the recently described failure of clinically
used antiangiogenics to extend the overall survival of human GBM patients.
PMID- 25117978
TI - Co-treatment with panitumumab and trastuzumab augments response to the MEK
inhibitor trametinib in a patient-derived xenograft model of pancreatic cancer.
AB - Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and epidermal growth
factor receptor (EGFR) family signaling are drivers of tumorigenesis in
pancreatic ductal adenocarcinoma (PDAC). Previous studies have demonstrated that
combinatorial treatment of PDAC xenografts with the mitogen-activated protein
kinase-extracellular-signal-regulated kinase (ERK) kinase1/2 (MEK1/2) inhibitor
trametinib and the dual EGFR/human epidermal growth factor receptor 2 (HER2)
inhibitor lapatinib provided more effective inhibition than either treatment
alone. In this study, we have used the therapeutic antibodies, panitumumab
(specific for EGFR) and trastuzumab (specific for HER2), to probe the role of
EGFR and HER2 signaling in the proliferation of patient-derived xenograft (PDX)
tumors. We show that dual anti-EGFR and anti-HER2 therapy significantly augmented
the growth inhibitory effects of the MEK1/2 inhibitor trametinib in three
different PDX tumors. While significant growth inhibition was observed in both
KRAS mutant xenograft groups receiving trametinib and dual antibody therapy
(tumors 366 and 608), tumor regression was observed in the KRAS wild-type
xenografts (tumor 738) treated in the same manner. Dual antibody therapy in
conjunction with trametinib was equally or more effective at inhibiting tumor
growth and with lower apparent toxicity than trametinib plus lapatinib. Together,
these studies provide further support for a role for EGFR and HER2 in pancreatic
cancer proliferation and underscore the importance of therapeutic intervention in
both the KRAS-rapidly accelerated fibrosarcoma kinase (RAF)-MEK-ERK and EGFR-HER2
pathways to achieve maximal therapeutic efficacy in patients.
PMID- 25117979
TI - SAMSN1 is a tumor suppressor gene in multiple myeloma.
AB - Multiple myeloma (MM), a hematological malignancy characterized by the clonal
growth of malignant plasma cells (PCs) in the bone marrow, is preceded by the
benign asymptomatic condition, monoclonal gammopathy of undetermined significance
(MGUS). Several genetic abnormalities have been identified as critical for the
development of MM; however, a number of these abnormalities are also found in
patients with MGUS, indicating that there are other, as yet unidentified, factors
that contribute to the onset of MM disease. In this study, we identify a Samsn1
gene deletion in the 5TGM1/C57BL/KaLwRij murine model of myeloma. In addition,
SAMSN1 expression is reduced in the malignant CD138+ PCs of patients with MM and
this reduced expression correlates to total PC burden. We identify promoter
methylation as a potential mechanism through which SAMSN1 expression is modulated
in human myeloma cell lines. Notably, re-expression of Samsn1 in the 5TGM1 murine
PC line resulted in complete inhibition of MM disease development in vivo and
decreased proliferation in stromal cell-PC co-cultures in vitro. This is the
first study to identify deletion of a key gene in the C57BL/KaLwRij mice that
also displays reduced gene expression in patients with MM and is therefore likely
to play an integral role in MM disease development.
PMID- 25117986
TI - Tissue vitamin concentrations are maintained constant by changing the urinary
excretion rate of vitamins in rats' restricted food intake.
AB - We previously reported that mild food restriction induces a reduction in
tryptophan-nicotinamide conversion, which helps to explain why death secondary to
pellagra is pandemic during the hungry season. In this study, we investigated the
levels of B-group vitamins in the liver, kidney, blood, and urine in rats that
underwent gradual restriction of food intake (80, 60, 40, and 20% restriction vs.
ad libitum food intake). No significant differences in the B-group vitamin
concentrations (mol/g tissue) in the liver and kidney were observed at any level
of food restriction. However, the urine excretion rates exhibited some
characteristic phenomena that differed by vitamin. These results show that the
tissue concentrations of B-group vitamins were kept constant by changing the
urinary elimination rates of vitamins under various levels of food restriction.
Only vitamin B12 was the only (exception).
PMID- 25117980
TI - Tumor interstitial fluid pressure-a link between tumor hypoxia, microvascular
density, and lymph node metastasis.
AB - High microvascular density (MVD) in the primary tumor has been shown to be
associated with increased incidence of lymph node metastases and poor clinical
outcome. Other investigations have revealed that a large fraction of hypoxic
tissue in the primary tumor is associated with metastatic disease and impaired
survival. These data are apparently incompatible because tumor hypoxia is
primarily a consequence of poor oxygen supply caused by an inadequate vasculature
with increased intervessel distances. Here, we provide an explanation of these
observations. Human melanoma xenografts were used as preclinical cancer models.
Tumors that metastasized to lymph nodes showed higher interstitial fluid pressure
(IFP) than those that did not metastasize, and compared with tumors with low IFP,
tumors with high IFP showed large hypoxic fractions centrally, high MVD in the
periphery, high peritumoral density of lymphatics, and elevated expression of
vascular endothelial growth factor A (VEGF-A) and VEGF-C. Significant
correlations were found between peripheral MVD and central hypoxia, and lymph
node metastasis was associated with high values of both parameters. These
findings suggest that the outcome of cancer may be associated with both high MVD
and extensive hypoxia in the primary tumor. We propose that proangiogenic factors
are upregulated in the tumor center and that the outward interstitial fluid flow
caused by the elevated IFP transports these factors to the tumor surface where
they evoke hemangiogenesis and lymphangiogenesis, and consequently, that the IFP
serves as a link between tumor hypoxia, peripheral tumor hemangiogenesis,
peritumoral lymphangiogenesis, and lymph node metastasis.
PMID- 25117987
TI - Timing of complementary food introduction and age at diagnosis of type 1
diabetes: the SEARCH nutrition ancillary study (SNAS).
AB - The association between timing of complementary food introduction and age at
diagnosis of type 1 diabetes was investigated among 1077 children in the SEARCH
for Diabetes in Youth study. Age at diagnosis was 5 months earlier for children
introduced to sugar-sweetened beverages (SSB) in the first 12 months of life
compared with those who were not (9.0+/-0.2 vs 9.5+/-0.1; P=0.02) independent of
human leukocyte antigen (HLA) risk status. Analyses stratified by HLA risk status
found that children with a high-risk HLA genotype had an earlier age at diagnosis
if they were introduced to fruit juice in the first year of life (mean age at
diagnosis=9.3+/-0.1, 9.1+/-0.1 and 9.6+/-0.2 for introduction at ?6 months,
between 7 and 11 months and ?12 months, respectively; P=0.04). Introduction of
SSB in the first year of life may accelerate the onset of type 1 diabetes
independent of HLA risk status.
PMID- 25117988
TI - Enteral nutrition within 72 h after onset of acute pancreatitis vs delayed
initiation.
AB - OBJECTIVES: To explore early (within 72 h) vs delayed enteral nutrition (EN)
therapy for patients with acute pancreatitis (AP). SUBJECTS/METHODS: A total of
93 patients were allocated to two groups: early enteral nutrition (EEN) group
(started within 72 h after onset) and delayed enteral nutrition (DEN) group
(started beyond 72 h but within 7 days after onset). Baseline parameters and
scores were recorded on admission and on day 3 after the initiation of EN
therapy, as were the clinical outcome variables. RESULTS: Hospital mortality,
length of stay, number of patients requiring mechanical ventilation and incidence
of pancreatic infection in the EEN group were significantly lower than those in
the DEN group; all six reported deaths were in the DEN group. In the DEN group,
more patients suffered from sepsis, shock or acute kidney injury, and more
patients required surgical intervention or continuous renal replacement therapy.
On day 3 after EN therapy was initiated, the acute physiology and chronic health
evaluation II scores, sequential organ failure assessment scores, C-reactive
protein levels and the incidence of bowel wall thickening were lower in the EEN
group than in the DEN group. The time when EN therapy was initiated was a
prognostic variable for pancreatic infection (odds ratio, 24.08; P=0.014).
CONCLUSIONS: Compared with the DEN therapy, EEN therapy can accelerate the
recovery of disturbed homeostasis, reduce the incidence of pancreatic infection
and improve the clinical outcomes of AP patients. For AP patients, EN therapy
should be initiated within 72 h after onset.
PMID- 25117989
TI - Dosimetric factors associated with weight loss during (chemo)radiotherapy
treatment for lung cancer.
AB - BACKGROUND/OBJECTIVES: Thoracic radiotherapy (RT) is associated with acute
toxicities, including oesophagitis, which can have an impact on nutritional
intake and subsequently lead to malnutrition. This study aimed to identify RT
dosimetric factors associated with ?5% weight loss in patients receiving
treatment for non-small-cell lung cancer (NSCLC). METHODS: Radiation dose data to
the oesophagus (including mean, maximum dose and oesophageal length) were
retrospectively analysed for a cohort of 54 NSCLC patients treated with
concurrent chemoradiotherapy between 2004 and 2006. Weight change was calculated
using the lowest weight during the 90 days from RT commencement compared with the
start of RT. RESULTS: Four patients for whom weight was not available at the
start or end of treatment were excluded, leaving 50 patients for analysis. The
prevalence of significant weight loss during the 90 days from RT commencement was
22% (median weight loss=9.1%, range=5.9-22.1). Dosimetric factors significantly
associated with ?5% weight loss were maximum dose to the oesophagus (P=0.046),
absolute oesophageal length receiving 40 Gy (odds ratio (OR)=1.18, P=0.04), 50 Gy
(OR=1.20, P=0.02) and 60 Gy (OR=1.32, P=0.005) to the partial circumference,
relative oesophageal length receiving 50 Gy (OR=1.03, P=0.03) and 60 Gy (OR=1.07,
P=0.005) to the partial circumference. CONCLUSIONS: Multiple dosimetric factors
were associated with significant weight loss. Of these factors, absolute and
relative length of the oesophagus receiving 60 Gy to the partial circumference
were more strongly related. Understanding the dosimetric factors associated with
weight loss may aid early identification and intervention in patients at
nutritional risk.
PMID- 25117990
TI - Body mass index and mild cognitive impairment-to-dementia progression in 24
months: a prospective study.
AB - BACKGROUND/OBJECTIVES: Mild cognitive impairment (MCI), often considered as an
early stage of dementia, is heterogeneous, and not all subjects with MCI progress
into clinically diagnosed dementia. Low body weight (and body mass index, BMI) as
well as losing weight while in MCI stadium have been proposed as possible risk
factors of MCI-to-dementia conversion. SUBJECTS/METHODS: A prospective, 2-year
observation of 102 MCI subjects has been conducted. Data on MCI subtype, somatic
and neuropsychiatric co-morbidity and demographic characteristics (including age,
gender and education), were collected. In addition, baseline and yearly BMI were
calculated. RESULTS: Data of 83 out of the originally included 102 subjects were
available after 2 years; 27 of those (32.5%) progressed to dementia. In
univariate analysis, multiple-deficit MCI subtype (as compared with pure
amnestic), higher age, the presence of diabetes and apathy, and lower baseline
BMI (and losing weight on 2-year follow-up) were associated with conversion to
dementia. Variables retained in the multivariate backward stepwise logistic
regression model for conversion after 24 months of observation included lower
baseline BMI (odds ratio, OR (95% cofidence interval, CI): 0.6 (0.4-0.9)), weight
loss on 2-year follow-up (OR (95% CI): 1.3 (1.1-1.5)), male gender (OR (95% CI):
0.1 (0.01-0.9)) and presence of apathy (OR (95% CI): 70.7 (5.6-699)). Apathetic
subjects had lower BMI and higher weight loss after controlling for potential
confounders (age, gender, years of education and baseline ADAS-cog (Alzheimer's
Disease Assessment Scale-cognitive subscale) score). CONCLUSION: MCI subjects
presenting with apathy, low initial BMI and losing weight on follow-up have a
significantly greater risk of developing dementia. Nutritional and behavioural
assessment should be considered as additional tools in evaluating the risk of
dementia among MCI subjects.
PMID- 25117991
TI - Effect of maternal n-3 long-chain polyunsaturated fatty acid supplementation
during pregnancy and/or lactation on adiposity in childhood: a systematic review
and meta-analysis of randomized controlled trials.
AB - It is hypothesized that prenatal and early postnatal exposure to n-3 long-chain
polyunsaturated fatty acids (LCPUFAs) is negatively associated with adiposity
later in life. We conducted a systematic review and meta-analysis to evaluate
whether maternal n-3 LCPUFA supplementation in pregnancy and/or lactation exerts
a beneficial effect on adiposity status in childhood. We searched six electronic
databases till 20 May 2014 for randomized controlled trials (RCTs) of n-3 LCPUFA
supplementation to pregnant and/or lactating women that reported data on body
mass index (BMI), waist circumference, sum of skinfold thicknesses or body fat
mass in children. Adiposity measures were grouped into three age categories:
preschool children (<5 years), school-aged children (6-12 years), and adolescents
(>13 years). Trial quality was assessed. We conducted fixed-effect and random
effects meta-analyses to combine study-specific estimates of differences between
the supplemented and control groups. A total of 6 RCTs (9 publications) involving
2847 participants were included. Summary estimates showed no effect of maternal
supplementation on BMI in preschool (standardized mean difference (SMD)=0.07, 95%
confidence interval (CI)=-0.22, 0.36, P=0.65) and school-aged children (SMD=0.12,
95% CI=-0.06, 0.30, P=0.20). Because of sparse data, it was not possible to pool
study results relating to other adiposity measures. There is currently no
evidence to support that n-3 LCPUFA supplementation during pregnancy and/or
lactation favourably affects child adiposity. Further high-quality trials are
needed.
PMID- 25117992
TI - Vitamin D status and associated factors of deficiency among Jordanian children of
preschool age.
AB - BACKGROUND/OBJECTIVES: Vitamin D deficiency in children remains a global concern.
Although literature exists on the vitamin D status and its risk factors among
children in the Middle East, findings have yielded mixed results, and large,
representative community studies are lacking. SUBJECTS/METHODS: In a nationally
representative survey of 1077 Jordanian children of preschool age (12-59 months)
in Spring 2010, we measured 25(OH)D3 concentrations by liquid chromatography
tandem mass spectrometry and calculated prevalence ratios for deficiency
associated with various factors. RESULTS: RESULTS showed 19.8% (95% confidence
interval (CI): 16.4-23.3%) deficiency (<12 ng/ml) and 56.5% (95% CI: 52.0-61.0%)
insufficiency (<20 ng/ml). In adjusted models, prevalence of deficiency was
higher for females compared with males (prevalence ratio (PR)=1.74, 95% CI: 1.22
2.47, P=0.002) and lower for children 24-35 months of age (PR=0.64, 95% CI: 0.44
0.92, P=0.018) compared with children 12-23 months of age. In rural areas, there
was no difference in prevalence of vitamin D deficiency between those whose
mothers had/did not have vitamin D deficiency (P=0.312); however, in urban areas,
prevalence of vitamin D deficiency was 3.18 times greater among those whose
mothers were vitamin D deficient compared with those whose mothers were not
deficient (P=0.000). CONCLUSIONS: Vitamin D deficiency and insufficiency pose
significant public health problems in Jordanian children with female children
disproportionately affected. Strong associations between vitamin D status in
children and urban residency and maternal vitamin D status suggest that the
behaviors related to sun exposure in urban mothers likely also affect the sun
exposure and thus vitamin D status of their children.
PMID- 25117993
TI - Household food insecurity and dietary diversity as correlates of maternal and
child undernutrition in rural Cambodia.
AB - OBJECTIVES: To assess household food insecurity and dietary diversity as
correlates of maternal and child anthropometric status and anemia in rural
Cambodia. METHODS: Trained interviewers administered a survey to 900 households
in four rural districts of Prey Veng, Cambodia. The Household Food Insecurity
Access Scale (HFIAS) and Household Dietary Diversity Score (HDDS) were used to
assess household food insecurity and dietary diversity. The height, weight and
hemoglobin concentration of the mother and youngest child under 5 years in each
household were measured. Multivariate logistic regression models were constructed
to assess the association between household food insecurity and dietary
diversity, and child stunting and wasting, maternal thinness, maternal and child
anemia. RESULTS: The mean (s.d.) HFIAS and HDDS scores were 5.3 (3.9) and 4.7
(1.6), respectively. The respective prevalences of mild, moderate and severe food
insecurity were 33, 37 and 12%. Maternal thinness, child stunting and child
wasting were present in 14.6, 25.4 and 8.1% of respondents, respectively. The
risk of maternal thinness, but not child stunting or wasting, increased as the
severity of household food insecurity increased. Household food insecurity was
also positively associated with maternal, but not child, anemia. Household
dietary diversity status was not significantly associated with any of the
outcomes we assessed. CONCLUSIONS: Efforts to improve household food security are
important as a means of promoting maternal nutritional status; however,
additional research is needed to better understand the role of other factors that
are driving the burden of child undernutrition in Cambodia.
PMID- 25117994
TI - Treatment of vitamin B12 deficiency-methylcobalamine? Cyancobalamine?
Hydroxocobalamin?-clearing the confusion.
AB - Vitamin B12 (cyancobalamin, Cbl) has two active co-enzyme forms, methylcobalamin
(MeCbl) and adenosylcobalamin (AdCbl). There has been a paradigm shift in the
treatment of vitamin B12 deficiency such that MeCbl is being extensively used and
promoted. This is despite the fact that both MeCbl and AdCbl are essential and
have distinct metabolic fates and functions. MeCbl is primarily involved along
with folate in hematopiesis and development of the brain during childhood.
Whereas deficiency of AdCbl disturbs the carbohydrate, fat and amino-acid
metabolism, and hence interferes with the formation of myelin. Thereby, it is
important to treat vitamin B12 deficiency with a combination of MeCbl and AdCbl
or hydroxocobalamin or Cbl. Regarding the route, it has been proved that the oral
route is comparable to the intramuscular route for rectifying vitamin B12
deficiency.
PMID- 25117995
TI - Body composition analysis in older adults with dementia. Anthropometry and
bioelectrical impedance analysis: a critical review.
AB - In clinical practice, geriatric nutritional assessment usually includes
nutritional screening, a simple anthropometric assessment, measurement of various
biochemical parameters, such as serum albumin, and sometimes (not always) body
composition analysis (BCA). However, there is a high prevalence of undiagnosed
malnutrition in patients with dementia. Several factors contribute to this
situation; probably, the most notable is the methodology used to assess body
composition (BC). In this regard, for BCA, techniques are needed that are
noninvasive, affordable, safe, simple and that require the minimum possible
collaboration by the elderly patient. Consequently, body mass index (BMI) and
waist circumference (WC) are widely used as indicators of overall and central
adiposity, respectively; however, there is no consensus on the cutoffs for the
elderly, and changes in BC (especially muscle-mass depletion) are masked by
normal values of BMI and WC. Bioimpedance analysis is a simple, cost-effective
and precise method for BCA, provided that cross-validated equations are used. Its
main disadvantage is that it is highly sensitive to changes in body water
(overhydration or dehydration), leading to substantial errors in BC estimates.
However, using Bioelectrical Impedance Vector Analysis errors are minimized, as
there is no need for the subject to be normally hydrated and it does not require
the use of predictive models.
PMID- 25117996
TI - Winter 25-hydroxyvitamin D levels in young urban adults are affected by smoking,
body mass index and educational level.
AB - BACKGROUND/OBJECTIVES: To study the relationship of winter 25
hydroxycholecalciferol (25-OHD) levels with age, education, place of residency,
marital status and body mass index (BMI) as they may affect sun exposure, vitamin
D synthesis and metabolism. SUBJECTS/METHODS: Subjects (1952) answered a
structured questionnaire concerning education, marital status and smoking; and
body weight/height, and parathyroid hormone and 25-OHD were measured. RESULTS: 25
OHD levels were higher in the males with elementary and secondary education
compared with higher education (46.8+/-18.5 and 43.7+/-16 vs 39.9+/-15.3 nmol/l,
P<0.01). Vitamin D deficiency was more prevalent (16.7%, (13.1-20.2) vs 10.8%,
(8.4-13.2), P=0.08) and sufficiency was less prevalent (24.6% (20-29.2) vs 33.7%,
(29.5-37.8), P=0.005) in those with higher than secondary education. No
differences were found among the females. Male smokers had lower 25-OHD than
nonsmokers (40.2+/-16.6 vs 43.6+/-15.7 nmol/l, P=0.004). Deficiency was more
prevalent in the male smokers than nonsmokers with secondary and higher education
(secondary 16.6%, (10.1-22.4) vs 8.2%, (5.1-11.3), P=0.006; higher 27.4%, (17.7
37.1) vs 13.2%, (9.0-17.5), P=0.003). 25-OHD was lower in the obese than in the
normal-weight females (34.6+/-16.2 vs 38.2+/-17.8 nmol/l, analysis of variance,
P=0.014), but not males. Marital status was not related to 25-OHD. Only in the
urban residents, increasing BMI in the young females increased the risk for
vitamin D deficiency by 1%, and smoking had an odds ratio of 1.99 (1.05-3.78) in
the young and 2.5 (1.07-5.75) in the middle-aged males. CONCLUSIONS: Smoking and
higher education in the males and obesity in the females were factors for vitamin
D deficiency among Bulgarian urban population.
PMID- 25117997
TI - Bioavailability of vitamin D2 from enriched mushrooms in prediabetic adults: a
randomized controlled trial.
AB - BACKGROUND/OBJECTIVES: Based on the growing evidence of risk reduction from fresh
fruit and vegetable consumption and an inverse relationship between serum 25
hydroxyvitamin D (25OHD) and the risk of type 2 diabetes (T2D), we determined the
benefits of regularly consuming vitamin D-enriched mushrooms in a prediabetic
cohort. Exposing edible mushrooms to ultraviolet B (UVB) light increases vitamin
D2 (D2) and raises serum 25OHD2 in healthy young adults; however, their benefit
to deficient prediabetics and glucose metabolism remains untested.
SUBJECTS/METHODS: Forty-three prediabetic, D-deficient adults (25OHD<=20 ng/ml),
BMI>25 were randomized to four groups consuming daily entrees containing 100 g
fresh sliced cooked mushrooms prepared by a chef for 16 weeks. Two groups were
fed UVB-treated mushrooms initially containing: 600 IU D2 or 4000 IU D2; each one
also received one capsule of placebo daily. Two control groups were fed untreated
mushrooms and D3 dietary supplements at two label doses: 600 IU D3 and 4000 IU
D3. D2 and D3 content were analyzed in mushrooms, before and after cooking and in
over-the-counter supplements. RESULTS: After 16 weeks, both D2-UVB-mushroom
entree doses, which were significantly lower after cooking, produced modest or no
increases in 25OHD2 or total 25OHD relative to the positive control subjects who
actually consumed about 1242 and 7320 IU per day of D3 (higher than stated on the
label). CONCLUSIONS: Unanticipated D2 cooking loss from fresh UVB mushrooms and
probable low absorption and/or hydroxylation may explain the smaller increase in
25OHD2 in our prediabetic overweight/obese cohort compared with past findings in
younger, healthy subjects. Moreover, no dose or vitamin D source was associated
with modifying T2D risk factors.
PMID- 25117998
TI - Associations of sugar-containing beverages with asthma prevalence in 11-year-old
children: the PIAMA birth cohort.
AB - BACKGROUND/OBJECTIVES: Recently, a few studies have linked soft drink consumption
to increased asthma risk, but the contribution of different types of soft drinks
is unknown. We investigated cross-sectional associations between six different
types of soft drinks and asthma in 11-year-old children. SUBJECTS/METHODS: We
analyzed data of 2406 children participating in the Dutch Prevention and
Incidence of Asthma and Mite Allergy birth cohort. At age 11, children self
reported consumption of sugar-added drinks, diet drinks, sweetened milk drinks,
100% fruit juice, energy drinks and sport drinks. The definition of asthma was
based on parental reports of wheezing, prescription of inhaled corticosteroids
and doctor's diagnosis of asthma. RESULTS: The prevalence of asthma in this study
was 5.8%. In adjusted logistic regression analyses, asthma risk was increased for
high (?10 glasses/week (gl/wk) versus low (<4 gl/wk) consumption of 100% fruit
juice (odds ratio (OR): 2.09, 95% confidence interval (CI): 1.21-3.60), sugar
added drinks (OR: 1.56, 95%CI: 0.95-2.56) and for very high (>21.5 gl/wk) versus
low (<12.5 gl/wk) total sugar-containing beverage (SCB) consumption (OR: 1.91,
95%CI: 1.04-3.48). Consumption of other beverages and consumption of fruit were
not associated with increased asthma risk. No evidence for mediation of the
observed associations by body mass index was found. CONCLUSIONS: This study
indicates that high consumption of 100% fruit juice and total SCBs is associated
with increased asthma risk in children. The positive association between
consumption of 100% fruit juice and asthma is an unexpected finding that needs
confirmation in future studies.
PMID- 25117999
TI - Omega-3 supplementation during the first 5 years of life and later academic
performance: a randomised controlled trial.
AB - BACKGROUND/OBJECTIVES: Consumption of oily fish more than once per week has been
shown to improve cognitive outcomes in children. However, it is unknown whether
similar benefits can be achieved by long-term omega-3 fatty acid supplementation.
The objective was to investigate the effect of omega-3 fatty acid supplementation
during the first 5 years of life on subsequent academic performance in children
by conducting a secondary analysis of the CAPS (Childhood Asthma Prevention
Study). SUBJECTS/METHODS: A total of 616 infants with a family history of asthma
were randomised to receive tuna fish oil (high in long-chain omega-3 fatty acids,
active) or Sunola oil (low in omega-3 fatty acids, control) from the time
breastfeeding ceased or at the age of 6 months until the age of 5 years. Academic
performance was measured by a nationally standardised assessment of literacy and
numeracy (National Assessment Program Literacy and Numeracy (NAPLAN)) in school
years 3, 5, 7 and 9. Plasma omega-3 fatty acid levels were measured at regular
intervals until 8 years of age. Between-group differences in test scores,
adjusted for maternal age, birth weight and maternal education, were estimated
using mixed-model regression. RESULTS: Among 239 children, there were no
significant differences in NAPLAN scores between active and control groups.
However, at 8 years, the proportion of omega-3 fatty acid in plasma was
positively associated with the NAPLAN score (0.13 s.d. unit increase in score per
1% absolute increase in plasma omega-3 fatty acid (95% CI 0.03, 0.23)).
CONCLUSIONS: Our findings do not support the practice of supplementing omega-3
fatty acids in the diet of young children to improve academic outcomes. Further
exploration is needed to understand the association between plasma omega-3 fatty
acid levels at 8 years and academic performance.
PMID- 25118001
TI - Prenatal diagnosis of 24 cases of microduplication 22q11.2: an investigation of
phenotype-genotype correlations.
AB - OBJECTIVE: Microduplication 22q11.2 is primarily characterized by a highly
variable clinical phenotype, which ranges from apparently normal or slightly
dysmorphic features (in the presence or absence of learning disorders) to severe
malformations with profound mental retardation. Hence, genetic counseling is
particularly challenging when microduplication 22q11.2 is identified in a
prenatal diagnosis. Here, we report on 24 prenatal cases of microduplication
22q11.2. METHODS: Seventeen of the cases were also reanalyzed by microarray
analysis, in order to determine copy number variations (CNVs, which are thought
to influence expressivity). We also searched for possible correlations between
fetal phenotypes, indications for invasive prenatal diagnosis, inheritance, and
pregnancy outcomes. RESULTS: Of the 24 cases, 15 were inherited, six occurred de
novo, and three were of unknown origin. Termination of pregnancy occurred in
seven cases and was mainly decided on the basis of ultrasound findings. Moreover,
additional CNVs were found in some patients and we try to make a genotype
phenotype correlation. CONCLUSION: We discuss the complexity of genetic
counseling for microduplication 22q11.2 and comment on possible explanations for
the clinical heterogeneity of this syndrome. In particular, we assessed the co
existence of additional CNVs and their contribution to phenotypic variations in
chromosome 22q11.2 microduplication syndrome.
PMID- 25118000
TI - Lung function, 25-hydroxyvitamin D concentrations and mortality in US adults.
AB - OBJECTIVE: To explore the associations between serum concentrations of vitamin D
(25(OH)D) and all-cause mortality among US adults defined by lung function (LF)
status, particularly among adults with obstructive LF (OLF). METHODS: Data from
10,795 adults aged 20-79 years (685 with restrictive LF (RLF) and 1309 with OLF)
who participated in the Third National Health and Nutrition Examination Survey
(1988-1994), had a spirometric examination, and were followed through 2006 were
included. RESULTS: During 14.2 years of follow-up, 1792 participants died. Mean
adjusted concentrations of 25(OH)D were 75.0 nmol/l (s.e. 0.7) for adults with
normal LF (NLF), 70.4 nmol/l (s.e. 1.8) for adults with RLF, 75.5 nmol/l (s.e.
1.5) for adults with mild obstruction and 71.0 nmol/l (s.e. 1.9) among adults
with moderate or worse obstruction (P=0.030). After adjustment for
sociodemographic factors, lifestyle factors, clinical variables and prevalent
chronic conditions, a concentration of <25 nmol/l compared with ? 75 nmol//l was
associated with mortality only among adults with NLF (hazard ratio (HR) 1.76; 95%
confidence interval (CI) 1.03, 3.00). Among participants with OLF, adjusted HRs
were 0.65 (95% CI 0.29, 1.48), 1.21 (95% CI 0.89, 1.66) and 0.97 (95% CI 0.78,
1.19) among those with concentrations <25, 25-<50 and 50-<75 nmol/l,
respectively. CONCLUSIONS: Baseline concentrations of 25(OH)D did not
significantly predict mortality among US adults with impaired LF.
PMID- 25118002
TI - Efficacy of silver-loaded nanofiber dressings in Candida albicans-contaminated
full-skin thickness rat burn wounds.
AB - In this experimental study, the effects of nanofiber dressings containing
different forms of silver on full-thickness rat burn contaminated with Candida
albicans was analyzed. A full-thickness skin burn was formed on a total of 32
Sprague-Dawley rats. After the burn wound was seeded with a 10 colony-forming
units/ml standard strain of Candida albicans ATCC90028, the animals were divided
into four groups. The effects of topical silver sulfadiazine and two recently
designed nanofiber dressings containing nanosilver and silversulfadiazine as
active materials were compared with the control group. There was a significant
difference in the Candida growth on the burn eschar tissue among the groups. The
difference for Candida growth in the burn eschar between the control group and
the 1% silver sulfadiazine-containing nanofiber dressing group was statistically
significant (P< 0.01). Silver sulfadiazine-containing nanofiber dressing was the
most effective agent in the treatment of Candida albicans-contaminated burn
wounds. Because of their regenerative potential, silver-loaded nanofiber
dressings could be a good alternative for infected burn wounds.
PMID- 25118003
TI - Using latent class analysis to develop a model of the relationship between
socioeconomic position and ethnicity: cross-sectional analyses from a multi
ethnic birth cohort study.
AB - BACKGROUND: Almost all studies in health research control or investigate
socioeconomic position (SEP) as exposure or confounder. Different measures of SEP
capture different aspects of the underlying construct, so efficient methodologies
to combine them are needed. SEP and ethnicity are strongly associated, however
not all measures of SEP may be appropriate for all ethnic groups. METHODS: We
used latent class analysis (LCA) to define subgroups of women with similar SEP
profiles using 19 measures of SEP. Data from 11,326 women were used, from eight
different ethnic groups but with the majority from White British (40%) or
Pakistani (45%) backgrounds, who were recruited during pregnancy to the Born in
Bradford birth cohort study. RESULTS: Five distinct SEP subclasses were
identified in the LCA: (i) "Least socioeconomically deprived and most educated"
(20%); (ii) "Employed and not materially deprived" (19%); (iii) "Employed and no
access to money" (16%); (iv) "Benefits and not materially deprived" (29%) and (v)
"Most economically deprived" (16%). Based on the magnitude of the point
estimates, the strongest associations were that compared to White British women,
Pakistani and Bangladeshi women were more likely to belong to groups: (iv)
"benefits and not materially deprived" (relative risk ratio (95% CI): 5.24 (4.44,
6.19) and 3.44 (2.37, 5.00), respectively) or (v) most deprived group (2.36
(1.96, 2.84) and 3.35 (2.21, 5.06) respectively) compared to the least deprived
class. White Other women were more than twice as likely to be in the (iv)
"benefits and not materially deprived group" compared to White British women and
all ethnic groups, other than the Mixed group, were less likely to be in the
(iii) "employed and not materially deprived" group than White British women.
CONCLUSIONS: LCA allows different aspects of an individual's SEP to be considered
in one multidimensional indicator, which can then be integrated in
epidemiological analyses. Ethnicity is strongly associated with these identified
subgroups. Findings from this study suggest a careful use of SEP measures in
health research, especially when looking at different ethnic groups. Further
replication of these findings is needed in other populations.
PMID- 25118005
TI - Biological Activities of Plant Pigments Betalains.
AB - Betalains are a family of natural pigments present in most plants of the order
Caryophyllales. They provide colors ranging from yellow to violet to structures
that in other plants are colored by anthocyanins. These include not only edible
fruits and roots but also flowers, stems, and bracts. The recent characterization
of different bioactivities in experiments with betalain containing extracts and
purified pigments has renewed the interest of the research community in these
molecules used by the food industry as natural colorants. Studies with multiple
cancer cell lines have demonstrated a high chemopreventive potential that finds
in vitro support in a strong antiradical and antioxidant activity. Experiments in
vivo with model animals and bioavailability studies reinforce the possible role
played by betalains in the diet. This work provides a critical review of all the
claimed biological activities of betalains, showing that the bioactivities
described might be supported by the high antiradical capacity of their structural
unit, betalamic acid. Although more investigations with purified compounds are
needed, the current evidences suggest a strong health-promoting potential.
PMID- 25118004
TI - Provision of KEL1-negative blood to obstetric patients: a 3-year single
institution retrospective review.
AB - BACKGROUND: KEL1 alloimmunization is a major cause of hemolytic disease of the
fetus and newborn (HDFN). While select countries have guidelines for preventing
transfusion-associated KEL1 alloimmunization, the United States does not. Beth
Israel Deaconess Medical Center instituted a policy in April 2009 whereby women
not more than 50 years of age on the obstetric service were transfused KEL1
negative red blood cells (RBCs). We sought to determine compliance and impact for
prevention of KEL1 alloimmunization and HDFN. STUDY DESIGN AND METHODS: All women
not more than 50 years of age without anti-K transfused RBCs during an obstetric
admission from April 9, 2009, to April 9, 2012, were identified (227). Adherence
to policy, factors contributing to nonadherence, and subsequent impact were
evaluated. For comparison, all cases of anti-K detection in women not more than
50 years of age admitted to nonobstetric services and all cases of transfusion
associated KEL1 alloimmunization in women not more than 50 years of age during
the 10 years prior were identified. RESULTS: Eighty-four percent received only
KEL1-negative units. Three (1.3%) women not more than 50 years of age on the
obstetric service were identified with anti-K, while 17 (1.5%) women not more
than 50 years of age on nonobstetric services had anti-K detected; only five of
20 had a prior RBC transfusion. In the 10 years prior, there were 27 cases of
transfusion-associated KEL1 alloimmunization in women not more than 50 years of
age. There were no cases of KEL1 HDFN in either period. CONCLUSION: Although the
findings demonstrate feasibility of providing KEL1-negative RBCs to women of
childbearing potential, evidence for clinical benefit is lacking. The low
prevalence of KEL1 in blood donors, the lack of significant differences in
alloimmunization rates, and no cases of HDFN during the study period questions
the clinical benefit of such a policy.
PMID- 25118006
TI - The rehabilitation role in chronic kidney and end stage renal disease.
AB - Chronic kidney disease (CKD) worldwide is rising markedly becoming a priority
public health problem. The progression of CKD cause functional limitation and
severe disability with poor quality of life. The aim of present review was to
highlight the effect of rehabilitation in CKD and ESRD subjects. The
rehabilitative process is unique in treating disabled people according to a
holistic approach with the aim of supporting a person's independent living and
autonomy. CKD are associated with an increased risk of functional impairment,
independent of age, gender, and co-morbidities. Clinicians should counsel
patients with CKD including frail elder people to increase physical activity
levels and target that regular physical activity including aerobic or endurance
exercises training benefits health. In old subjects with CKD and multiple
functional impairments, the traditional disease based model should be changed to
individualized patient-centered approach that prioritizes patient preferences.
Patients receiving haemodialysis have a considerably lower exercise tolerance,
functional capacity, and more muscle wasting than healthy subjects or patients
with less severe CKD. Exercise training or comprehensive multi-dimensional
strategy and goal-oriented intervention should be also provided in ESRD older
subjects. Structured prevention programs based on reducing the risk factors for
CKD and rehabilitative strategies could reduce disability occurrence.
PMID- 25118007
TI - Familial co-segregation of Coffin-Lowry syndrome inherited from the mother and
autosomal dominant Waardenburg type IV syndrome due to deletion of EDNRB
inherited from the father.
AB - We report an African-American family that was identified after the proposita was
referred for diagnostic evaluation at 41/2 months with a history of Hirschsprung
and dysmorphic features typical of Waardenburg syndrome (WS). Family evaluation
revealed that the father had heterochromidia irides and hypertelorism supporting
the clinical diagnosis of WS; however, examination of the mother revealed
characteristic facial and digital features of Coffin-Lowry syndrome (CLS).
Molecular testing of the mother identified a novel 2 bp deletion (c.865_866delCA)
in codon 289 of RPS6KA3 leading to a frame-shift and premature termination of
translation 5 codons downstream (NM_004586.2:p.Gln289ValfsX5). This deletion also
was identified in the proposita and her three sisters with a clinical suspicion
of CLS, all of whom as carriers for this X-linked disorder had very subtle
manifestations. The molecular confirmation of WS type 4 (Shah-Waardenburg; WS4)
was not as straightforward. To evaluate WS types 1-4, multiple sequential
molecular tests were requested, including Sanger sequencing of all exons, and
deletion/duplication analysis using MLPA for PAX3, MITF, SOX10, EDN3 and EDNRB.
Although sequencing did not identify any disease causing variants, MLPA
identified a heterozygous deletion of the entire EDNRB in the father. This
deletion was also found in the proposita and the oldest child. Since the
heterozygous deletion was the only change identified in EDNRB, this family
represents one of the few cases of an autosomal dominant inheritance of WS4
involving the endothelin pathway. Altogether, clinical evaluation of the family
revealed one child to be positive for WS4 and two positive for CLS, while two
children were positive for both diseases simultaneously (including the proposita)
while another pair test negative for either disease. This kinship is an example
of the coincidence of two conditions co-segregating in one family, with variable
phenotypes requiring molecular testing to confirm the clinical diagnoses.
PMID- 25118008
TI - NKX2.5 mutation identification on exome sequencing in a patient with heterotaxy.
AB - Exome sequencing enables us to screen most of the protein coding genes in an
unbiased way, this technique represents an ideal tool to identify previously
under- or unappreciated phenotypes associated with known disease genes and
genetic disorders. Here we present an illustrative case that required exome
sequencing to identify a genetic alteration associated with the clinical
features. The phenotype of the proband included heterotaxy, double outlet right
ventricle, common atrioventricular canal, total anomalous pulmonary venous
connection, asplenia, failure to thrive and short stature. Exome sequencing
demonstrated a frameshift mutation c.397_400del (p.P133GfsTer 42) in NKX2.5.
Although a single previous case of heterotaxy was reported in a large familial
case of NKX2.5, heterotaxy is not clinically appreciated to be a part of the
phenotypic spectrum associated with NKX2.5 mutations. This case report
demonstrates the utility of exome sequencing in expanding a phenotypic spectrum
of a known Mendelian disorder. We predict that this type of unexpected
identification of mutations in known-disease associated genes in patients with
atypical or expanded phenotypes will occur with increasing frequency as the use
of exome and genome sequencing become more common tools in diagnosing patients
with syndromic and non-syndromic foms of structural birth defects.
PMID- 25118009
TI - Modelling the effects of cochlear implant current focusing.
AB - OBJECTIVES: A finite element model of the human coiled cochlea was used to model
the voltage distribution due to stimulation by the individual electrodes of a
cochlear implant. The scalar position of the electrode array was also varied in
order to investigate its effect on the voltage distribution. Multi-electrode
current focusing methods were then investigated, with the aim of increasing
spatial selectivity. METHODS: Simultaneous current focusing is initially
achieved, as in previous publications, by calculating the input currents to the
22 electrodes that best separates the voltages at these electrode positions. The
benefits of this electrode focusing strategy do not, however, entirely carry over
to the predicted voltage distributions at the position of the spiral ganglion
cells, where excitation is believed to occur. A novel focusing strategy is then
simulated, which compensates for the impedances between the currents at the
electrode sites and the voltage distribution directly at the position of the
spiral ganglion cells. RESULTS: The new strategy produces much better focusing at
the sites of the spiral ganglion cells, as expected, but at the cost of increased
current requirements. Regularization was introduced in order to reduce current
requirements, which also reduced the sensitivity of the solution to uncertainties
in the impedance matrix, so that improved focusing was achieved with similar
current requirements to that of electrode focusing. DISCUSSION: Although such
focusing strategies cannot be achieved in practice at the moment, since the
responses from the electrodes to the neural sites cannot be determined with
currently available recording methods, these results do support the feasibility
of a more effective focusing strategy, which may provide improved spectral
resolution leading to improved perception of sound.
PMID- 25118010
TI - Occurrence and expression of bacterial human virulence gene homologues in natural
soil bacteria.
AB - The presence and in vitro expression of homologues to 22 bacterial human
virulence determinants amongst culturable soil bacteria were investigated. About
25% of the bacterial isolates contained virulence gene homologues representing
toxin (hblA, cytK2), adhesin (fimH), regulator (phoQ) and resistance (yfbI)
determinants in pathogenic bacteria. The homologues of the toxin genes were found
in Actinobacteria and Firmicutes (hblA), and in Firmicutes and Alpha- and
Gammaproteobacteria (cytK2). The homologues to the type 1 fimbrial adhesin gene,
fimH, and the L-Ara4N transferase gene, yfbI, were observed in Actinobacteria,
Firmicutes and Gammaproteobacteria. The regulator gene, phoQ, was only found in
Gammaproteobacteria. The presence of cytK2 in Alpha- and Gammaproteobacteria,
fimH in Actinobacteria and Firmicutes, and hblA in Actinobacteria has not
previously been described. A close sequence similarity (84-100%) was observed
between the genes of environmental and clinical isolates, and expression assays
suggested that the genes in some cases were expressed in vitro. The presence of
functional virulence gene homologues underpins their importance for the survival
of environmental bacteria. Furthermore, the high degree of sequence conservation
to clinical sequences indicates that natural environments may be 'evolutionary
cribs' of emerging pathogens.
PMID- 25118017
TI - Genetic and environmental contributions to social anxiety across different ages:
a meta-analytic approach to twin data.
AB - Social anxiety disorder (SAD) and social anxiety symptoms (SAS) have been largely
studied both epidemiologically and genetically, however, estimates of genetic and
environmental influences for these phenotypes widely vary across reports. Based
upon available literature, 13 cohorts (42,585 subjects) were included in 3 meta
analytic estimates of the standardized variance components of aetiological
influences on SAD/SAS, on the effect of age and of phenotype (symptoms vs.
diagnosis). The proportions of variance accounted for by genetic and
environmental factors were calculated by averaging estimates among studies, and
pondered by the number of individuals in each sample. Meta-analytic estimations
showed that genetic and non-shared environmental factors explain most of
individual differences for SAD/SAS. In adults, the genetic contribution was half
than that in younger patients, with higher contribution of non-shared
environmental influences. In contrast, the shared environmental factors seem to
be less relevant.
PMID- 25118016
TI - Successful treatment of post-transplant thrombocytopenia with romiplostim in a
pediatric patient with X-linked chronic granulomatous disease.
AB - Thrombocytopenia is a frequent complication following HSCT in pediatric patients.
Romiplostim is a TPO receptor agonist that has been utilized successfully in the
treatment of pediatric patients with immune thrombocytopenia. We describe a three
yr-old male with X-linked CGD treated with an unrelated donor bone marrow
transplant. His course was complicated by the development of symptomatic
thrombocytopenia. He was started on romiplostim with prompt improvement in his
thrombocytopenia. We found the use of romiplostim to be an effective and safe
alternative to the potential complications as well as morbidity and mortality
associated with the use of immunosuppressive agents such as corticosteroids.
PMID- 25118019
TI - On the state of scientific English and how to improve it - Part 7: Separating key
concepts and qualifications.
PMID- 25118018
TI - In vitro anticancer activity of loquat tea by inducing apoptosis in human
leukemia cells.
AB - Fresh loquat leaves have been used as folk health herb in Asian countries for
long time, although the evidence supporting their functions is still minimal.
This study aimed to clarify the chemopreventive effect of loquat tea extract
(LTE) by investigating the inhibition on proliferation, and underlying mechanisms
in human promyelocytic leukemia cells (HL-60). LTE inhibited proliferation of HL
60 in a dose-dependent manner. Molecular data showed that the isolated fraction
of LTE induced apoptosis of HL-60 as characterized by DNA fragmentation;
activation of caspase-3, -8, and -9; and inactivation of poly(ADP)ribose
polymerase. Moreover, LTE fraction increased the ratio of pro-apoptotic Bcl-2
associated X protein (Bax)/anti-apoptotic myeloid cell leukemia 1 (Mcl-1) that
caused mitochondrial membrane potential loss and cytochrome c released to
cytosol. Thus, our data indicate that LTE might induce apoptosis in HL-60 cells
through a mitochondrial dysfunction pathway. These findings enhance our
understanding for chemopreventive function of loquat tea.
PMID- 25118020
TI - A polymerization chaperone: A novel hypothesis for the +TIP network (comment on
DOI 10.1002/bies.201400029).
PMID- 25118024
TI - Tectonic gene mutations in patients with Joubert syndrome.
AB - So far very few patients with sequence variants in the closely related tectonic
genes TCTN1-3 have been described. By multi-gene panel next-generation sequencing
(NGS) in patients with Joubert syndrome, we identified two more patients and
summarize what is currently known about the phenotypes associated with sequence
variants in these genes. In a boy aged 12 years with intellectual disability and
the classical molar tooth sign on MRI, a homozygous splice-site sequence variant
in TCTN3 leading to in-frame skipping of exon 7 was detected. A previously
described non-truncating sequence variant in TCTN3 was also associated with
Joubert syndrome, whereas four truncating sequence variants were detected in
patients with Meckel-Gruber or Mohr-Majewski syndrome. The second patient, a boy
aged 7 years with severe psychomotor retardation, was found to carry a homozygous
canonic splice-site sequence variant in TCTN2. So far, only three sequence
variants associated with Joubert syndrome and two with Meckel-Gruber syndrome
have been described in this gene. Reviewing the clinical data on patients with
sequence variants in the tectonic genes TCTN1-3 reveals that all of them have a
neurological phenotype with vermis hypoplasia or occipital encephalocele
associated with severe intellectual disability in the surviving patients. In
contrast, other features frequently seen in patients with ciliopathies such as
nephronophthisis, liver fibrosis, retinal dystrophy or coloboma have not been
reported. Our patients emphasize the usefulness and efficacy of a comprehensive
NGS panel approach. A concise genetic diagnosis may help to prevent unnecessary
investigations and improve the clinical management of these patients.
PMID- 25118025
TI - VPS35 and DNAJC13 disease-causing variants in essential tremor.
AB - Exome-sequencing analyses have identified vacuolar protein sorting 35 homolog
(VPS35) and DnaJ (Hsp40) homolog, subfamily C, member 13 (DNAJC13) harboring
disease-causing variants for Parkinson disease (PD). Owing to the suggested
clinical, pathological and genetic overlap between PD and essential tremor (ET)
we assessed the presence of two VPS35 and DNAJC13 disease-causing variants in ET
patients. TaqMan probes were used to genotype VPS35 c.1858G>A (p.(D620N))
(rs188286943) and DNAJC13 c.2564A>G (p.(N855S)) (rs387907571) in 571 ET patients
of European descent, and microsatellite markers were used to define the disease
haplotype in variant carriers. Genotyping of DNAJC13 identified two ET patients
harboring the c.2564A>G (p.(N855S)) variant previously identified in PD patients.
Both patients appear to share the disease haplotype previously reported. ET
patients with the VPS35 c.1858G>A (p.(D620N)) variants were not observed.
Although a genetic link between PD and ET has been suggested, DNAJC13 c.2564A>G
(p.(N855S)) represents the first disease-causing variant identified in both, and
suggests the regulation of clathrin dynamics and endosomal trafficking in the
pathophysiology of a subset of ET patients.
PMID- 25118026
TI - Regions of homozygosity identified by oligonucleotide SNP arrays: evaluating the
incidence and clinical utility.
AB - Copy neutral segments with allelic homozygosity, also known as regions of
homozygosity (ROHs), are frequently identified in cases interrogated by
oligonucleotide single-nucleotide polymorphism (oligo-SNP) microarrays. Presence
of ROHs may be because of parental relatedness, chromosomal recombination or
rearrangements and provides important clues regarding ancestral homozygosity,
consanguinity or uniparental disomy. In this study of 14 574 consecutive cases,
832 (6%) were found to harbor one or more ROHs over 10 Mb, of which 651 cases
(78%) had multiple ROHs, likely because of identity by descent (IBD), and 181
cases (22%) with ROHs involving a single chromosome. Parental relatedness was
predicted to be first degree or closer in 5%, second in 9% and third in 19%. Of
the 181 cases, 19 had ROHs for a whole chromosome revealing uniparental isodisomy
(isoUPD). In all, 25 cases had significant ROHs involving a single chromosome; 5
cases were molecularly confirmed to have a mixed iso- and heteroUPD15 and 1 case
each with segmental UPD9pat and segmental UPD22mat; 17 cases were suspected to
have a mixed iso- and heteroUPD including 2 cases with small supernumerary marker
and 2 cases with mosaic trisomy. For chromosome 15, 12 (92%) of 13 molecularly
studied cases had either Prader-Willi or Angelman syndrome. Autosomal recessive
disorders were confirmed in seven of nine cases from eight families because of
the finding of suspected gene within a ROH. This study demonstrates that ROHs are
much more frequent than previously recognized and often reflect parental
relatedness, ascertain autosomal recessive diseases or unravel UPD in many cases.
PMID- 25118027
TI - The phenotype of congenital insensitivity to pain due to the NaV1.9 variant
p.L811P.
PMID- 25118028
TI - Malan syndrome: Sotos-like overgrowth with de novo NFIX sequence variants and
deletions in six new patients and a review of the literature.
AB - De novo monoallelic variants in NFIX cause two distinct syndromes. Whole gene
deletions, nonsense variants and missense variants affecting the DNA-binding
domain have been seen in association with a Sotos-like phenotype that we propose
is referred to as Malan syndrome. Frameshift and splice-site variants thought to
avoid nonsense-mediated RNA decay have been seen in Marshall-Smith syndrome. We
report six additional patients with Malan syndrome and de novo NFIX deletions or
sequence variants and review the 20 patients now reported. The phenotype is
characterised by moderate postnatal overgrowth and macrocephaly. Median height
and head circumference in childhood are 2.0 and 2.3 standard deviations (SD)
above the mean, respectively. There is overlap of the facial phenotype with NSD1
positive Sotos syndrome in some cases including a prominent forehead, high
anterior hairline, downslanting palpebral fissures and prominent chin. Neonatal
feeding difficulties and/or hypotonia have been reported in 30% of patients.
Developmental delay/learning disability have been reported in all cases and are
typically moderate. Ocular phenotypes are common, including strabismus (65%),
nystagmus (25% ) and optic disc pallor/hypoplasia (25%). Other recurrent features
include pectus excavatum (40%) and scoliosis (25%). Eight reported patients have
a deletion also encompassing CACNA1A, haploinsufficiency of which causes episodic
ataxia type 2 or familial hemiplegic migraine. One previous case had episodic
ataxia and one case we report has had cyclical vomiting responsive to pizotifen.
In individuals with this contiguous gene deletion syndrome, awareness of possible
later neurological manifestations is important, although their penetrance is not
yet clear.
PMID- 25118029
TI - Characterization of the first intragenic SATB2 duplication in a girl with
intellectual disability, nearly absent speech and suspected hypodontia.
AB - SATB2, a gene encoding a highly conserved DNA-binding protein, is known to have
an important role in craniofacial and neuronal development. Only a few patients
with SATB2 variants have been described so far. Recently, Docker et al provided a
summary of these patients and delineated the SAS (SATB2-associated syndrome). We
here report on a girl with intellectual disability, nearly absent speech and
suspected hypodontia who was shown to carry an intragenic SATB2 tandem
duplication hypothesized to lead to haploinsufficiency of SATB2. Preliminary
information on this patient had already been included in the article by Docker et
al. We want to give a detailed description of the patient's phenotype and
genotype, providing further insight into the spectrum of the molecular mechanisms
leading to SAS.
PMID- 25118031
TI - Short-term trained lexical categories produce preattentive categorical perception
of color: evidence from ERPs.
AB - The present study investigated whether short-term trained lexical categories
could produce lateralized preattentive categorical perception (CP) of color.
Participants' event-related potentials were recorded while performing a visual
oddball task in which standard and deviant colored stimuli from the same or
different novel lexical categories were presented. Two groups of participants
were recruited: a group trained on these novel categories (n = 26), and an
untrained control group (n = 26). Results of paired t tests showed that deviants
did not evoke significant visual mismatch negativity, with the exception of
deviants from different novel categories presented in the right visual field of
the training group. This suggests that short-term trained lexical categories
produce lateralized preattentive color CP, and language enhances sensitivity to
the differences among between-category stimuli.
PMID- 25118030
TI - Isolated dentinogenesis imperfecta and dentin dysplasia: revision of the
classification.
AB - Dentinogenesis imperfecta is an autosomal dominant disease characterized by
severe hypomineralization of dentin and altered dentin structure. Dentin extra
cellular matrix is composed of 90% of collagen type I and 10% of non-collagenous
proteins among which dentin sialoprotein (DSP), dentin glycoprotein (DGP) and
dentin phosphoprotein (DPP) are crucial in dentinogenesis. These proteins are
encoded by a single gene: dentin sialophosphoprotein (DSPP) and undergo several
post-translational modifications such as glycosylation and phosphorylation to
contribute and to control mineralization. Human mutations of this DSPP gene are
responsible for three isolated dentinal diseases classified by Shield in 1973:
type II and III dentinogenesis imperfecta and type II dentin dysplasia. Shield
classification was based on clinical phenotypes observed in patient. Genetics
results show now that these three diseases are a severity variation of the same
pathology. So this review aims to revise and to propose a new classification of
the isolated forms of DI to simplify diagnosis for practitioners.
PMID- 25118034
TI - A missed opportunity? Recognizing pregnancy-associated cardiovascular risk
factors.
PMID- 25118032
TI - Iodine nutritional status after the implementation of the new iodized salt
concentration standard in Zhejiang Province, China.
AB - BACKGROUND: Iodine deficiencies were prevalent in China until the introduction of
universal salt iodization (USI) in 1995. In 2012, the standard salt iodine
concentration was adjusted to 20-30 mg/kg. The success of USI for the control of
iodine deficiency disorders requires monitoring its effect at a population level.
METHODS: Two cross sectional surveys of a representative sample of children aged
8-10 years in Zhejiang Province were carried out in 2011 and 2013. Data on
participants' socio-demographic characteristics were collected from the children
using a structured questionnaire. Spot urine samples were collected and delivered
to local Center for Disease Control and Prevention laboratory for measuring
urinary iodine concentration. In 2011, out of 420 selected children aged 8-10
years, 391 were recorded and provided urine samples. In 2013, out of 1560
selected children aged 8-10 years, 1556 were recorded and provided urine samples.
RESULTS: The median urinary iodine concentration of subjects in the 2013 survey
was 174.3 MUg/L, significantly lower than that of 2011(p = 0.000). The median
urinary iodine concentration of subjects living in urban and rural areas in the
2013 survey was 169.0 MUg/L, and 186.1 MUg/L respectively, significantly lower
than that of 2011 only for subjects living in urban areas (p = 0.000). There were
no significant differences for subjects living in rural areas in the survey in
2011 and in 2013 (p = 0.086). CONCLUSIONS: At the time the new local iodization
policy put forward, iodine nutrition was generally adequate in both urban and
rural areas, suggesting that the new policy for adjusting the standard salt
iodine concentration is effective. Our data also indicate that the reason people
living in urban areas had a lower urinary iodine concentration than people in
rural areas may be due to their preference for using non-iodized salt in the last
2 or 3 years. Maintaining USI at an appropriate level is an important part of
preventing iodine deficiency disorders and should always be based on regular
monitoring and comparison of urinary iodine concentration by province.
PMID- 25118035
TI - 20 things you didn't know about women and heart disease.
PMID- 25118037
TI - A "nephrological" approach to physical activity.
AB - Despite consensus among nephrologists that exercise is important and probably
beneficial for their patients, assessment of physical function or encouragement
of physical activity is not a part of the routine management of patients with
CKD. In order to plan an useful strategy for exercise training we need to clearly
define some questions. First of all, nephrologists need to be aware of physical
exercise benefits; lack of motivation and increased perceived risk by health care
professionals have been identified as contributing factors to physical
inactivity. Moreover, the main elements necessary for sustaining exercise
programs in this population have to take in account, such as the requirement of
exercise professionals, equipment and space, individual prescription, adequate
commitment from dialysis and medical staff. When PA may not be implemented, a
comprehensive, individualized occupational therapy program may improve functional
independence and activity of daily living. Finally, physical function has to be
careful monitored and assesses by medical staff.
PMID- 25118036
TI - Long-term reproducible expression in human fetal liver hematopoietic stem cells
with a UCOE-based lentiviral vector.
AB - Hematopoietic Stem Cell (HSC) targeted gene transfer is an attractive treatment
option for a number of hematopoietic disorders caused by single gene defects.
However, extensive methylation of promoter sequences results in silencing of
therapeutic gene expression. The choice of an appropriate promoter is therefore
crucial for reproducible, stable and long-term transgene expression in clinical
gene therapy. Recent studies suggest efficient and stable expression of
transgenes from the ubiquitous chromatin opening element (UCOE) derived from the
human HNRPA2B1-CBX3 locus can be achieved in murine HSC. Here, we compared the
use of HNRPA2B1-CBX3 UCOE (A2UCOE)-mediated transgene regulation to two other
frequently used promoters namely EF1alpha and PGK in human fetal liver-derived
HSC (hflHSC). Efficient transduction of hflHSC with a lentiviral vector
containing an HNRPA2B1-CBX3 UCOE-eGFP (A2UCOE-eGFP) cassette was achieved at
higher levels than that obtained with umbilical cord blood derived HSC (3.1x;
p<0.001). While hflHSC were readily transduced with all three test vectors
(A2UCOE-eGFP, PGK-eGFP and EF1alpha-eGFP), only the A2-UCOE construct
demonstrated sustained transgene expression in vitro over 24 days (p<0.001). In
contrast, within 10 days in culture a rapid decline in transgene expression in
both PGK-eGFP and EF1alpha-eGFP transduced hflHSC was seen. Subsequently,
injection of transduced cells into immunodeficient mice (NOD/SCID/Il2rg-/-)
demonstrated sustained eGFP expression for the A2UCOE-eGFP group up to 10 months
post transplantation whereas PGK-eGFP and EF1alpha-eGFP transduced hflHSC showed
a 5.1 and 22.2 fold reduction respectively over the same time period. We conclude
that the A2UCOE allows a more efficient and stable expression in hflHSC to be
achieved than either the PGK or EF1alpha promoters and at lower vector copy
number per cell.
PMID- 25118038
TI - Identification of colonic fibroblast secretomes reveals secretory factors
regulating colon cancer cell proliferation.
AB - Stromal microenvironment influences tumor cell proliferation and migration.
Fibroblasts represent the most abundant stromal constituents. Here, we
established two pairs of normal fibroblast (NF) and cancer-associated fibroblast
(CAF) cultures from colorectal adenocarcinoma tissues and the normal
counterparts. The NFs and CAFs were stained positive for typical fibroblast
markers and inhibited colon cancer (CC) cell proliferation in in vitro cocultures
and in xenograft mouse models. The fibroblast conditioned media were analyzed
using LC-MS and 227 proteins were identified at a false discovery rate of 1.3%,
including 131 putative secretory and 20 plasma membrane proteins. These proteins
were enriched for functional categories of extracellular matrix, adhesion, cell
motion, inflammatory response, redox homeostasis and peptidase inhibitor.
Secreted protein acidic and rich in cysteine, transgelin, follistatin-related
protein 1 (FSTL1) and decorin was abundant in the fibroblast secretome as
confirmed by Western blot. Silencing of FSTL1 and transgelin in colonic
fibroblast cell line CCD-18Co induced an accelerated proliferation of CC cells in
cocultures. Exogenous FSTL1 attenuates CC cell proliferation in a negative
fashion. FSTL1 was upregulated in CC patient plasma and cancerous tissues but had
no implication in prognosis. Our results provided novel insights into the
molecular signatures and modulatory role of CC associated fibroblasts. BIOLOGICAL
SIGNIFICANCE: In this study, a label-free LC-MS was performed to analyze the
secretomes of two paired primary fibroblasts, which were isolated from fresh
surgical specimen of colorectal adenocarcinoma and adjacent normal colonic
tissues and exhibited negative modulatory activity for colon cancer cell growth
in in vitro cocultures and in vivo xenograph mouse models. Follistatin-related
protein 1 was further revealed to be one of the stroma-derived factors of
potential suppression role for colon cancer cell proliferation. Our results
provide novel insights into the molecular signatures and the modulatory role of
colon cancer associated fibroblasts, and establish a valuable resource for the
development of therapeutic agents or novel clinic biomarker.
PMID- 25118040
TI - How much is it going to cost me? Bidirectional relations between adolescents'
moral personality and prosocial behavior.
AB - The current study examined bidirectional relations between adolescents' moral
personality (prosocial values, self-regulation, and sympathy) and low- and high
cost prosocial behavior toward strangers. Participants included 682 adolescents
(M age of child = 14.31, SD = 1.07, 50% female) who participated at two time
points, approximately one year apart. Cross-lag analyses suggested that
adolescents' values were associated with both low- and high-cost prosocial
behavior one year later, self-regulation was associated with high-cost prosocial
behavior, and sympathy was associated with low-cost prosocial behavior. Findings
also suggested that low-cost prosocial behavior was associated with sympathy one
year later, and high-cost prosocial behavior was associated with values.
Discussion focuses on reciprocal relations between moral personality and
prosocial behavior, and the need to consider a more multidimensional approach to
prosocial development during adolescence.
PMID- 25118039
TI - Increased methylation of the MOR gene proximal promoter in primary sensory
neurons plays a crucial role in the decreased analgesic effect of opioids in
neuropathic pain.
AB - BACKGROUND: The analgesic potency of opioids is reduced in neuropathic pain.
However, the molecular mechanism is not well understood. RESULTS: The present
study demonstrated that increased methylation of the Mu opioid receptor (MOR)
gene proximal promoter (PP) in dorsal root ganglion (DRG) plays a crucial role in
the decreased morphine analgesia. Subcutaneous (s.c.), intrathecal (i.t.) and
intraplantar (i.pl.), not intracerebroventricular (i.c.v.) injection of morphine,
the potency of morphine analgesia was significantly reduced in nerve-injured mice
compared with control sham-operated mice. After peripheral nerve injury, we
observed a decreased expression of MOR protein and mRNA, accompanied by an
increased methylation status of MOR gene PP, in DRG. However, peripheral nerve
injury could not induce a decreased expression of MOR mRNA in the spinal cord.
Treatment with 5-aza-2'-deoxycytidine (5-aza-dC), inhibited the increased
methylation of MOR gene PP and prevented the decreased expression of MOR in DRG,
thereby improved systemic, spinal and periphery morphine analgesia. CONCLUSIONS:
Altogether, our results demonstrate that increased methylation of the MOR gene PP
in DRG is required for the decreased morphine analgesia in neuropathic pain.
PMID- 25118041
TI - Single night video-game use leads to sleep loss and attention deficits in older
adolescents.
AB - The present study investigated adolescent video-game use prior to bedtime and
subsequent sleep, working memory and sustained attention performance.
Participants were 21 healthy, good-sleeping adolescents (16 male) aged between 15
and 20 years (M = 17.6 years, SD = 1.8). Time spent video-gaming and subsequent
sleep was measured across one night in the sleep laboratory. There were
significant correlations between time spent video-gaming and sleep and between
video-gaming and sustained attention, but not working memory. Sleep duration, in
turn, had a significant negative association with sustained attention
performance. Mediation analyses revealed that the relationship between video
gaming and sustained attention was fully mediated by sleep duration. These
results indicate that video-gaming affected the ability to sustain attention only
in as much as it affected sleep. In order to minimise negative consequences of
video-game playing, video-games should be used in moderation, avoiding use close
to the sleep period, to obviate detriments to sleep and performance.
PMID- 25118042
TI - Assessment of 'Fitting to Outcomes Expert' FOXTM with new cochlear implant users
in a multi-centre study.
AB - OBJECTIVE: To compare the fitting time requirements and the efficiency in
achieving improvements in speech perception during the first 6 months after
initial stimulation of computer-assisted fitting with the Fitting to Outcome
eXpert' (FOX) and a standard clinical fitting procedure. METHOD: Twenty-seven
post-lingually deafened adults, newly implanted recipients of the Advanced
Bionics HiRes 90KTM cochlear implant from Germany, the UK, and France took part
in a controlled, randomized, clinical study. Speech perception was measured for
all participants and fitting times were compared across groups programmed using
FOX and conventional programming methods. RESULTS: The fitting time for FOX was
significantly reduced at 14 days (P < 0.001) but equivalent over the 6-month
period. The groups were not well matched for duration of deafness; therefore,
speech perception could not be compared across groups. DISCUSSION: Despite
including more objective measures of performance than a standard fitting approach
and the adjustment of a greater range of parameters during initial fitting, FOX
did not add to the overall fitting time when compared to the conventional
approach. FOX significantly reduced the fitting time in the first 2 weeks and by
providing a standard fitting protocol, reduced variability across centres.
CONCLUSIONS: FOX computer-assisted fitting can be successfully used at switch on,
in different clinical environments, reducing fitting time in the first 2 weeks
and is efficient at providing a usable program.
PMID- 25118044
TI - Binding of nucleobases with graphene and carbon nanotube: a review of
computational studies.
AB - Functionalized carbon nanotubes (CNTs) constitute a new class of nanostructured
materials that have vast applications in CNT purification and separation,
biosensing, drug delivery, etc. Hybrids formed from the functionalization of CNT
with biological molecules have shown interesting properties and have attracted
great attention in recent years. Of particular interest is the hybridization of
single- or double-stranded nucleic acid (NA) with CNT. Nucleobases, as the
building blocks of NA, interact with CNT and contribute strongly to the stability
of the NA-CNT hybrids and their properties. In this work, we present a thorough
review of previous studies on the binding of nucleobases with graphene and CNT,
with a focus on the simulation works that attempted to evaluate the structure and
strength of binding. Discrepancies among these works are identified, and factors
that might contribute to such discrepancies are discussed.
PMID- 25118045
TI - A polymerized ionic liquid-supported B12 catalyst with a ruthenium trisbipyridine
photosensitizer for photocatalytic dechlorination in ionic liquids.
AB - By immobilizing a B12 complex and a Ru(ii) trisbipyridine photosensitizer in a
polymerized ionic liquid (PIL), a visible light-driven photocatalyst was
developed. The synthesized copolymer was characterized by GPC and DLS, and using
UV-vis absorption spectra and luminescence spectra. The Ru(ii) trisbipyridine
photosensitizer in the copolymer showed an enhanced emission compared to that of
the monomer in the ionic liquid, 1-butyl-4-methylimidazolium
bis(trifluoromethanesulfonyl)amide ([C4mim][NTf2]). Formation of the Co(i)
species of the B12 complex in the copolymer was confirmed by the UV-vis spectral
change in [C4mim][NTf2] containing a sacrificial reductant (triethanolamine)
under irradiation with visible light. The copolymer showed a high photocatalytic
activity in various ionic liquids for 1,1-bis(4-chlorophenyl)-2,2,2
trichloroethane (DDT) dechlorination with ~99% conversion after visible light
irradiation for 2 h. Furthermore, both the B12 catalyst and photosensitizer in
the polymer were easily recycled for use with the ionic liquid solvent without
any loss of catalytic activity.
PMID- 25118043
TI - Contrasting diversity of epibiotic bacteria and surrounding bacterioplankton of a
common submerged macrophyte, Potamogeton crispus, in freshwater lakes.
AB - Epibiotic bacteria on surfaces of submerged macrophytes play important roles in
the ecological processes of shallow lakes. However, their community ecology and
dynamics are far from understood in comparison with those of bacterioplankton.
Here, we conducted a comparative study of the species diversity and composition
of epibiotic bacterial and the surrounding bacterioplankton communities of a
common submerged macrophyte, Potamogeton crispus, in 12 lakes at a regional scale
in China. We found that in different freshwater lakes, epibiotic bacteria
possessed higher taxonomic richness than bacterioplankton did. There existed a
marked divergence in the community structure between epibiotic bacteria and
bacterioplankton. Alphaproteobacteria was the most dominant group for epibiotic
bacteria, whereas Actinobacteria dominated bacterioplankton. Although variations
in both bacterioplankton and epibiotic bacterial community compositions in
different lakes were better explained by environmental than spatial factors, both
environment and space had more intensified effects on epibiotic bacteria. This
implied more complex and diverse 'microhabitats' for epibiotic bacteria on
surfaces of submerged macrophytes, which may lead to higher variations of
epibiotic bacteria than bacterioplankton. Our study suggested that epibiotic
bacteria exhibited higher diversity and distinct community composition than the
surrounding bacterioplankton. More attention should be focused on the productive
and diverse microbial habitats on submerged macrophytes.
PMID- 25118046
TI - Four pediatric patients with autosomal recessive polycystic kidney disease
developed new-onset diabetes after renal transplantation.
AB - NODAT is increasingly prevalent. Compared with adult recipients, NODAT is less
prevalent in pediatric renal transplant recipients; however, some risk factors
for its development in young patients have been defined. We report four pediatric
renal transplant recipients with ARPKD who developed NODAT. We review the current
pediatric NODAT literature and hypothesize that ARPKD may be an additional risk
factor for NODAT.
PMID- 25118050
TI - Of early animals, anaerobic mitochondria, and a modern sponge.
AB - The origin and early evolution of animals marks an important event in life's
history. This event is historically associated with an important variable in
Earth history - oxygen. One view has it that an increase in oceanic oxygen levels
at the end of the Neoproterozoic Era (roughly 600 million years ago) allowed
animals to become large and leave fossils. How important was oxygen for the
process of early animal evolution? New data show that some modern sponges can
survive for several weeks at low oxygen levels. Many groups of animals have
mechanisms to cope with low oxygen or anoxia, and very often, mitochondria -
organelles usually associated with oxygen - are involved in anaerobic energy
metabolism in animals. It is a good time to refresh our memory about the
anaerobic capacities of mitochondria in modern animals and how that might relate
to the ecology of early metazoans.
PMID- 25118051
TI - Expertise in video game playing is associated with reduced valence-concordant
emotional expressivity.
AB - In carefully selected groups of video game playing (VGP) experts and nonexperts,
we examined valence-concordant emotional expressivity. We measured
electromyographic (EMG) activity over the corrugator supercilii muscle while
participants viewed pleasant, neutral, and unpleasant pictures. Potential group
differences concerning valence-concordant expressivity may arise from differences
concerning the participants' emotional reactivity. To control for such
differences, we concomitantly measured skin conductance response (SCR) and, in a
separate affect misattribution procedure (AMP), valence transfer from the same
set of stimuli. Importantly, we found attenuated valence-concordant EMG activity
over the corrugator supercilii muscle in VGP experts compared to nonexperts, but
no differences were evident concerning SCR or valence transfer in the AMP. The
findings suggest that expertise in VGP is particularly associated with reduced
valence-concordant emotional expressivity.
PMID- 25118052
TI - Increased myo-inositol in parietal white and gray matter as a biomarker of poor
prognosis in neuropsychiatric lupus: a case report.
AB - Neuropsychiatric manifestations can be a serious complication of systemic lupus
erythematosus, affecting nearly 56% of these patients. Frequently, acceptable
clinical outcome is observed in neurolupus with immunosuppressive therapy.
Different metabolites identified with MR spectroscopy may be associated with
modifications in the natural history of this disease, specifically in the central
nervous system. We report a case of neurolupus with progressive neurologic
impairment despite aggressive immunosuppressive treatment. We describe clinical
features, laboratory and MRI results, as well as characteristic findings on MR
spectroscopy. Serial MRI identified atrophy of the left temporal lobe. MR
spectroscopy showed an increase of myo-inositol/creatine ratio intensity,
accompanied by a decrease of N-acetylaspartate/creatine ratio in both parietal
white and gray matter. During follow-up, the patient developed progressive
cognitive deficiency despite the intensification of therapy. Neurolupus
manifestations are common and immunosuppressive treatment often avoids severe
complications. Characteristic findings on MR spectroscopy may be useful for
clinicians to determine poor prognosis and resistance to therapy.
PMID- 25118053
TI - Higher BMI in heart failure patients is associated with longer survival only in
the absence of diabetes.
AB - AIMS: Obesity and diabetes are associated with an increased cardiovascular risk
and mortality. Paradoxically, higher BMI is associated with longer survival in
heart failure patients. The association between BMI and risk of death in heart
failure patients depends on diabetes history. METHODS: We conducted a
retrospective cohort study on 503 ambulatory systolic heart failure patients
attending a heart failure clinic, based on abstraction of data from clinical
records. Patients were compared according to diabetes history. BMI was analyzed
as a continuous variable and dichotomized using 25 kg/m as cut-off. Patients'
follow-up was censored at 5 years and all-cause death was the endpoint under
study. RESULTS: The median age was 69 years and 68% were men; 184 (36.6%)
patients had diabetes upon referral. During follow-up, 95 nondiabetic and 69
diabetic patients died. Higher BMI was associated with longer survival in the
whole sample, but this association was only reproduced in the subgroup of
patients without diabetes [hazard ratio = 0.93; 95% confidence interval (CI):
0.89-0.98 per kg/m vs. hazard ratio = 0.99; 95% CI: 0.94-1.04 in diabetic
patients; P for interaction = 0.009]. BMI below 25 kg/m increased the risk of
death by 1.90-fold (95% CI: 1.23-2.94) with a null association in diabetic
patients (P for interaction = 0.012). The association between BMI and mortality
in nondiabetic heart failure patients was independent of other predictors of
prognosis. CONCLUSION: The reported obesity paradox in heart failure can only be
observed in nondiabetic patients.
PMID- 25118054
TI - A national Programme Budgeting and Marginal Analysis (PBMA) of health improvement
spending across Wales: disinvestment and reinvestment across the life course.
AB - BACKGROUND: Wales faces serious public health challenges, with relatively low
life expectancies and wide inequalities in life expectancy with associated
pressures on the National Health Service (NHS) at a time of financial recession.
This has led to growing recognition of the need to better understand the range of
health improvement and prevention programmes across Welsh Government, NHS, local
government and voluntary sector agencies. METHODS: The Minister for Health and
Social Care commissioned Public Health Wales, the single national public health
organisation, to establish a Health Improvement Advisory Group, to oversee a
Programme Budgeting and Marginal Analysis (PBMA) expert panel. The panel drew on
evidence from a range of sources to explore potential alternative modes of health
improvement initiative delivery across Wales. Electronic voting was used to agree
an appropriate time horizon for health improvement programme outcomes, main
objective of the health improvement review and criteria for evaluating candidate
services for disinvestment and investment. The panel also used electronic voting
to state whether they wished to disinvest or invest in a candidate service.
RESULTS: The review identified a budget of L15.1 million, spanning 10 Welsh
Government priority areas, and 6 life course stages. Due to lack of evidence the
panel recommended total disinvestment in 7 out of 25 initiatives releasing L1.5
million of resources, and partial disinvestment in a further 3 interventions
releasing L7.3 million of resources. The panel did not recommend increasing
investment in any of the 25 initiatives under review. Marginal analyses
prioritised child health, mental health and wellbeing and tobacco control as key
areas for investment. CONCLUSIONS: Wales is championing a concept of "prudent
healthcare". The PBMA exercise undertaken here was a transparent evidence-based
tool to reach decisions about potential for disinvestment and reinvestment in
health improvement strategies. It also demonstrates the potential wider
application at a national level across government public health functions, to
ensure resources are most cost-effectively deployed, with due consideration for
equity.
PMID- 25118055
TI - Fitness for entering a simple exercise program and mortality: a study corollary
to the exercise introduction to enhance performance in dialysis (EXCITE) trial.
AB - BACKGROUND/AIMS: In this corollary analysis of the EXCITE study, we looked at
possible differences in baseline risk factors and mortality between subjects
excluded from the trial because non-eligible (n=216) or because eligible but
refusing to participate (n=116). METHODS: Baseline characteristics and mortality
data were recorded. Survival and independent predictors of mortality were
assessed by Kaplan-Meier and Cox regression analyses. RESULTS: The incidence rate
of mortality was higher in non-eligible vs. eligible non-randomized patients
(21.0 vs. 10.9 deaths/100 persons-year; P<0.001). The crude excess risk of death
in non-eligible patients (HR 1.96; 95% CI 1.36 to 2.77; P<0.001) was reduced
after adjustment for risk factors which differed in the two cohorts including
age, blood pressure, phosphate, CRP, smoking, diabetes, triglycerides,
cardiovascular comorbidities and history of neoplasia (HR 1.60; 95% CI 1.10 to
2.35; P=0.017) and almost nullified after including in the same model also
information on deambulation impairment (HR 1.16; 95% CI 0.75 to 1.80; P=0.513).
CONCLUSIONS: Deambulation ability mostly explains the difference in survival rate
in non-eligible and eligible non-randomized patients in the EXCITE trial.
Extending data analyses and outcome reporting also to subjects not taking part in
a trial may be helpful to assess the representability of the study population.
PMID- 25118056
TI - Genomic Resources Notes accepted 1 June 2014 - 31 July 2014.
AB - This article documents the public availability of transcriptome sequence data,
assembled contigs and annotated contigs and ORFS for five anchialine shrimp
species (Crustacea: Atyidae and Alpheidae).
PMID- 25118057
TI - Microsurgical clipping for recurrent aneurysms after initial endovascular coil
embolization.
AB - OBJECTIVE: Surgical treatment for recurrent lesions of embolized aneurysms is
difficult and challenging for many neurosurgeons because intra-aneurysmal coil
masses are sometimes scarred to the wall of the aneurysm or adherent to adjacent
vital structures. To assess the efficacy and safety of surgical treatment without
coil removal for recurrent aneurysms after previous coil embolization, we
retrospectively studied clinical results, angiographic results, and complications
in patients treated with additional microsurgical clipping. METHODS: From April
2003 to April 2013, 7 patients with recurrent previous embolized aneurysms
underwent microsurgical treatment. RESULTS: This series included 1 man and 6
women receiving endovascular coiling as the first-line treatment. One patient's
aneurysm was unruptured, whereas the other 6 were ruptured. The aneurysm
locations were posterior communicating (n = 3), anterior communicating (n = 2),
ophthalmic (n = 1), and posterior inferior cerebellar (n = 1). The initial sizes
ranged from 3-11.5 mm in diameter (mean, 6.6 mm), and the aspect ratios were 1.2
to 3.4 (mean, 1.9). In these aneurysms, the initial coiling result was complete
occlusion in 5 patients, and neck remnants in 2 patients. The mechanism
underlying aneurysm recurrence was coil compaction in 3 aneurysms, aneurysm
regrowth in 3 aneurysms, and fundal migration in 1 aneurysm. The median
recurrence latency was 28.8 months (range, 0.7-115 months). Microsurgical
clippings without coil removal were used in 6 patients; a parent artery occlusion
under bypass protection was done in 1 case with a posterior inferior cerebellar
aneurysm. Fenestrated clips in combination with another type of clip were
successfully used for 4 of 6 patients who were treated with direct neck clipping.
No postoperative morbidity was observed, and postoperative imaging studies
revealed complete occlusion of the aneurysms in all cases. There were no
recurrences of aneurysms during the follow-up period (mean, 44.7 months; range,
0.5-118 months). CONCLUSIONS: The microsurgical clipping without coil removal for
recurrent lesions of embolized aneurysms is effective and safe when it is
technically feasible. The tandem clipping in combination with a fenestrated clip
is a crucial method for direct neck clipping without coil removal for previously
coiled recurrent aneurysms. For unclippable lesions, a parent artery occlusion
under bypass protection should be taken into consideration.
PMID- 25118058
TI - Gelfoam scaffold for vein prolapse during brain tumor surgery.
AB - When resecting gliomas, extra-axial tumors, or their overlying cortex, cortical
veins may become suspended over the resection cavity and ultimately prolapse and
kink into the cavity, promoting venous thrombosis. To prevent this, we describe a
technique to secure a Gelfoam scaffold beneath the cortical vein at the edge of
the resection cavity to prevent kinking and possible thrombosis from taking place
after tumor removal. Depending on the diameter of the resection cavity, this can
be done at 1 or both edges of the resection cavity to prevent prolapse of the
vein into the cavity. In our experience with this technique, during the past 10
years, there have been no cases of venous thrombosis after tumor removal on
postoperative imaging or clinical examination.
PMID- 25118059
TI - Efficacy and safety of subdural drains after burr-hole evacuation of chronic
subdural hematomas: systematic review and meta-analysis of randomized controlled
trials.
AB - OBJECTIVE: To determine whether the use of a subdural drain after burr-hole
evacuation of a chronic subdural hematoma is safe and effective in preventing
recurrence and subsequent operations, and as such improving functional outcomes.
METHODS: The literature search included the following databases: PubMed, the
National Institutes of Health/National Library of Medicine, Clinical Trials
Registry, CENTRAL (The Cochrane Library), EMBASE, and LILACS. The search was
performed in June 2013, and did not have restrictions or filters with regard to
language or year of publication. Methodologic quality was assessed through the
Jadad's scale. Primary outcomes were recurrence and reoperation rates. Secondary
outcomes were functional outcome, mortality, and postoperative complications.
Results were presented as pooled Mantel-Haenszel relative risks (RR), with 95%
confidence intervals (95% CI). RESULTS: A total of 7 randomized controlled trials
were analyzed. Three studies were classified as high methodologic quality and
four as low quality. Pooled RR were symptomatic recurrence (RR 0.51; 95% CI 0.36
0.75), reoperation (RR 0.5; 95% CI 0.34-0.74), poor functional outcome (RR 0.61,
95% CI 0.39-0.98), mortality (RR 0.67, 95% CI 0.37-1.22), and postoperative
complications (RR 1.28, 95% CI 0.78-2.11). There was no statistically significant
heterogeneity within the outcomes. CONCLUSIONS: The meta-analysis demonstrates
that the insertion of a subdural drain was associated with a statistically
significant reduction in the risk of symptomatic recurrence and the requirement
for further surgical intervention of chronic subdural hematoma after surgical
evacuation. Furthermore, it was associated with statistically significant
improvements in both short-term and long-term functional outcome.
PMID- 25118060
TI - Spinal metastases in breast cancer: single center experience.
AB - OBJECTIVE: Metastases to the spine are a common manifestation of breast cancer
leading to considerable reduction in the patient's quality of life. Physicians
must consider the different treatments available to decrease pain, reduce tumor
burden, and ensure spinal stability to prevent neurological compromises. The
first objective of this study is to analyze the epidemiology and outcomes of
patients with spinal metastases from breast cancer and describe changes over time
in these lesions. The second objective is to establish the current treatment of
spinal metastases in this type of cancer. METHODS: A total of 140 patients with
breast cancer and spinal metastasis involvement were studied retrospectively.
Demographic, clinical, and radiologic parameters were assessed, and the effects
of systemic and local treatments on spinal metastasis were analyzed. RESULTS:
Median patient age at diagnosis of breast cancer was 50 years (19-86 years) and
average follow-up was 100 months (4-384 months). Median overall survival after
diagnosis of spinal metastasis was 18.6 months. Fractures were present in 24
patients (19.3%) at diagnosis and in up to 60 cases (48.6%) by the end of the
study period. CONCLUSIONS: The survival rate was better in patients with spinal
metastases who received specific treatment. The evolution from lytic spinal
metastasis to mixed and blastic subtypes is observed with adjunctive therapy for
spinal metastases (bisphosphonates, radiotherapy). Increased attention must be
given for high-grade breast cancer, as spinal metastases declare faster for these
stages. This study provides evidence that a multidisciplinary tumor board
specifically focusing on bone metastasis is essential to effectively manage
patients with breast cancer and spinal metastasis.
PMID- 25118061
TI - Endolithic bacterial communities in rock coatings from Karkevagge, Swedish
Lapland.
AB - Rock coatings in Karkevagge, Swedish Lapland, are widespread and mineralogically
diverse. A preliminary study of the rock coatings revealed higher than expected
bacterial diversity for an endolithic environment in the arctic. Using 454 Roche
pyrosequencing of the 16S rRNA gene, nine rock coating samples from three
different coating mineralogies were sequenced. The three coating types include Fe
films of goethite and hematite, sulfate crusts of jarosite and gypsum, and
aluminum glazes of basaluminite and alunite. Over 20,000 quality sequences were
analyzed, and over 2800 operational taxonomic units were identified. Diversity
indices and richness estimates confirmed high levels of diversity, particularly
in the sulfate crusts with diversity indices at the level of complex soils.
Inferred physiology shows the presence of both heterotrophs and autotrophs, with
genera of autotrophic Fe and S metabolisms present in at least 2% of the total
for each coating type. The most common phyla included Proteobacteria,
Acidobacteria, and Actinobacteria - all common soil taxa. Coatings also showed
distinct community structure between coating mineralogies. Given the diversity in
coating types found in areas receiving the same chemical and environmental
inputs, the distinct microbial communities suggest a biological role in coating
development.
PMID- 25118066
TI - Technological supports to promote choice opportunities by two children with
fragile X syndrome and severe to profound developmental disabilities.
AB - This study was aimed at assessing whether technological supports (i.e. optic
sensors such as photocells) were successful enabling two boys with fragile X
syndrome and severe to profound developmental disabilities to perform occupation
and choice opportunities. A second goal of the study was to reduce stereotyped
behaviours (i.e. hand mouthing and eye poking) exhibited by the participants.
Finally, the third purpose of the study was to verify the rehabilitative effects
of the intervention program on the indices of happiness of the participants. The
study has been conducted according to a non-concurrent multiple baseline design
across participants followed by intervention and cross over phases, where the
associations between behavioural responses and environmental consequences were
systematically inverted. Moreover, a maintenance phase was assessed. The results
demonstrated that the technology is useful to facilitate employment and
opportunities of choice, showing a growth of the indices of happiness and a
decrease of stereotyped behaviours, from both participants involved. Clinical,
practical and psychological implications of the findings are discussed.
PMID- 25118067
TI - The Effect of Increasing Fruit and Vegetable Consumption on Overall Diet: A
Systematic Review and Meta-analysis.
AB - Increasing fruit and vegetable (FV) consumption is associated with reduced risk
of major diseases. However, it is unclear if health benefits are related to
increased micronutrient intake or to improvements in overall diet profile. This
review aimed to assess if increasing FV consumption had an impact on diet
profile. In the systematic review, 12 studies revealed increases in micronutrient
intakes, whilst the meta-analysis confirmed macronutrient findings from the
systematic review showing no significant difference between the intervention and
control groups in energy (kcals) in seven studies (mean difference = 1 kcals [95%
CI = -115, 117]; p = 0.98), significant decreases in total fat (% energy) in five
studies (Mean difference = -4% [95% CI = -5, -3]; p = < 0.00001) and significant
increases in fiber in six studies (Mean difference = 5.36 g [95% CI = 4, 7]; p =
< 0.00001) and total carbohydrate (% energy) in four studies (Mean = 4% [95% CI=
2, 5]; p = < 0.00001). In conclusion, results indicate that increased FV
consumption increases micronutrient, carbohydrate and fiber intakes and possibly
reduces fat intake, with no overall effect on energy intake. Therefore health
benefits may act through an improvement in overall diet profile alongside
increased micronutrient intakes.
PMID- 25118068
TI - Synchronous tRNA movements during translocation on the ribosome are orchestrated
by elongation factor G and GTP hydrolysis.
AB - The translocation of tRNAs through the ribosome proceeds through numerous small
steps in which tRNAs gradually shift their positions on the small and large
ribosomal subunits. The most urgent questions are: (i) whether these
intermediates are important; (ii) how the ribosomal translocase, the GTPase
elongation factor G (EF-G), promotes directed movement; and (iii) how the energy
of GTP hydrolysis is coupled to movement. In the light of recent advances in
biophysical and structural studies, we argue that intermediate states of
translocation are snapshots of dynamic fluctuations that guide the movement. In
contrast to current models of stepwise translocation, kinetic evidence shows that
the tRNAs move synchronously on the two ribosomal subunits in a rapid reaction
orchestrated by EF-G and GTP hydrolysis. EF-G combines the energy regimes of a
GTPase and a motor protein and facilitates tRNA movement by a combination of
directed Brownian ratchet and power stroke mechanisms.
PMID- 25118070
TI - Challenges for paediatric transplantation in Africa.
AB - Transplantation is the accepted mode of treatment for patients with end-stage
organ disease affecting the heart, lungs, kidney, pancreas, liver and intestine.
Long-term outcomes have significantly improved and the aim of management is no
longer only long-term survival, but also focuses on quality of life especially in
children. Transplantation in Africa faces a number of challenges including wide
socioeconomic disparity, lack of legislation around brain death and organ
donation in many countries, shortage of skilled medical personnel and facilities,
infectious disease burden and insecure access to and monitoring of
immunosuppression. Whilst there is a need for transplantation, the establishment
and sustainability of transplant programmes require careful planning with
national government and institutional support. Legislation regarding brain death
diagnosis and organ retrieval/donation; appropriate training of the transplant
team; and transparent and equitable criteria for organ allocation are important
to establish before embarking on a transplant programme. Establishing
sustainable, self-sufficient transplant programmes in Africa with equal access to
all citizens is an important step towards curtailing transplant tourism and organ
trafficking and has a further beneficial effect in raising the level of medical
and surgical care in these countries.
PMID- 25118069
TI - How does conversion of natural tropical rainforest ecosystems affect soil
bacterial and fungal communities in the Nile river watershed of Uganda?
AB - Uganda's forests are globally important for their conservation values but are
under pressure from increasing human population and consumption. In this study,
we examine how conversion of natural forest affects soil bacterial and fungal
communities. Comparisons in paired natural forest and human-converted sites among
four locations indicated that natural forest soils consistently had higher pH,
organic carbon, nitrogen, and calcium, although variation among sites was large.
Despite these differences, no effect on the diversity of dominant taxa for either
bacterial or fungal communities was detected, using polymerase chain reaction
denaturing gradient gel electrophoresis (PCR-DGGE). Composition of fungal
communities did generally appear different in converted sites, but surprisingly,
we did not observe a consistent pattern among sites. The spatial distribution of
some taxa and community composition was associated with soil pH, organic carbon,
phosphorus and sodium, suggesting that changes in soil communities were nuanced
and require more robust metagenomic methods to understand the various components
of the community. Given the close geographic proximity of the paired sampling
sites, the similarity between natural and converted sites might be due to
continued dispersal between treatments. Fungal communities showed greater
environmental differentiation than bacterial communities, particularly according
to soil pH. We detected biotic homogenization in converted ecosystems and
substantial contribution of beta-diversity to total diversity, indicating
considerable geographic structure in soil biota in these forest communities.
Overall, our results suggest that soil microbial communities are relatively
resilient to forest conversion and despite a substantial and consistent change in
the soil environment, the effects of conversion differed widely among sites. The
substantial difference in soil chemistry, with generally lower nutrient quantity
in converted sites, does bring into question, how long this resilience will last.
PMID- 25118071
TI - An evaluation of traffic-awareness campaign videos: empathy induction is
associated with brain function within superior temporal sulcus.
AB - Acting appropriately within social contexts requires an ability to appreciate
others' mental and emotional states. Indeed, some campaign programs designed to
reduce anti-social behaviour seek to elicit empathy for the victims. The
effectiveness of these campaigns can be evaluated according to the degree to
which they induce such responses, but by applying neuroscientific techniques this
can be done at the behavioural and neurophysiological level. Neuroimaging studies
aimed at identifying the neural mechanisms behind such socio-cognitive and
emotional processes frequently reveal the role of the superior temporal sulcus
(STS). We applied this knowledge to assess the effectiveness of traffic-awareness
campaign adverts to induce empathic expression. Functional magnetic resonance
imaging (fMRI) data were acquired from 20 healthy male volunteers as they watched
these campaign videos consisting of a dramatic sequence of events and
catastrophic endings, and control videos without such dramatic endings. Among
other structures, a significantly greater neural response was observed within
bilateral STS, particularly within the right hemisphere, during the observation
of campaign relative to control videos. Furthermore, activation in these brain
regions correlated with the subjects' empathic expression. Our results develop
our understanding of the role of STS in social cognition. Moreover, our data
demonstrate the utility of neuroscientific methods when evaluating the
effectiveness of campaign videos in terms of their ability to elicit empathic
responses. Our study also demonstrates the utility of these specific stimuli for
future neuroscientific research.
PMID- 25118073
TI - Forced sex, rape and sexual exploitation: attitudes and experiences of high
school students in South Kivu, Democratic Republic of Congo.
AB - This paper reports on fieldwork carried out in 2011 with the aim of investigating
the attitudes and reported behaviour of Congolese high school students concerning
sexual relationships. A total of 56 boys and girls aged 16-20 from two urban and
two rural high schools in South Kivu Province took part in focus groups, and 40
of these were subsequently interviewed individually. The majority of boys felt
that they were entitled to sex from their girlfriends and that if persuasion was
unsuccessful, the use of force was legitimate; this, in their minds, did not
constitute rape. Girls, on the other hand, were clear that such forced sex was
rape. However it may be understood, rape was perceived as having increased in
recent years and was explained by weak legal systems, pornography and provocative
dressing by girls. Boys were angry at the competition from older, often married,
men who were able to provide monetary and other incentives to the girls.
PMID- 25118074
TI - Suicide in Sri Lanka 1975-2012: age, period and cohort analysis of police and
hospital data.
AB - BACKGROUND: Sri Lanka has experienced major changes in its suicide rates since
the 1970s, and in 1995 it had one of the highest rates in the world. Subsequent
reductions in Sri Lanka's suicide rates have been attributed to the introduction
of restrictions on the availability of highly toxic pesticides. We investigate
these changes in suicide rates in relation to age, gender, method specific trends
and birth-cohort and period effects, with the aim of informing preventative
strategies. METHODS: Secular trends of suicide in relation to age, sex, method,
birth-cohort and period effects were investigated graphically using police data
(1975-2012). Poisoning case-fatality was investigated using national hospital
admission data (2004-2010). RESULTS: There were marked changes to the age-,
gender- and method-specific incidence of suicide over the study period. Year on
year declines in rates began in 17-25 year olds in the early 1980s. Reduction in
older age groups followed and falls in all age groups occurred after all class I
(the most toxic) pesticides were banned. Distinct changes in the age/gender
pattern of suicide are observed: in the 1980s suicide rates were highest in 21-35
year old men; by the 2000s, this pattern had reversed with a stepwise increase in
male rates with increasing age. Throughout the study period female rates were
highest in 17-25 year olds. There has been a rise in suicide by hanging, though
this rise is relatively small in relation to the marked decline in self-poisoning
deaths. The patterns of suicides are more consistent with a period rather than
birth-cohort effect. CONCLUSIONS: The epidemiology of suicide in Sri Lanka has
changed noticeably in the last 30 years. The introduction of pesticide
regulations in Sri Lanka coincides with a reduction in suicide rates, with
evidence of limited method substitution.
PMID- 25118072
TI - An evolving perspective about the origins of childhood undernutrition and
nutritional interventions that includes the gut microbiome.
AB - The Sackler Institute for Nutrition Science and the World Health Organization
(WHO) have worked together to formulate a research agenda for nutrition science.
Undernutrition of children has profound effects on health, development, and
achievement of full human capacity. Undernutrition is not simply caused by a lack
of food, but results from a complex interplay of intra- and intergenerational
factors. Representative preclinical models and comprehensive well-controlled
longitudinal clinical studies are needed to further understand the contributions
and the interrelationships among these factors and to develop interventions that
are effective and durable. This paper summarizes work on mechanisms underlying
the varied manifestations of childhood undernutrition and discusses current gaps
in knowledge and challenges to our understanding of undernutrition and
infection/immunity throughout the human life cycle, focusing on early childhood
growth. It proposes a series of basic and clinical studies to address this global
health challenge.
PMID- 25118075
TI - Viunalikeviruses are environmentally common agents of horizontal gene transfer in
pathogens and biocontrol bacteria.
AB - Bacteriophages have been used as natural biocontrol and therapeutic agents, but
also as biotechnological tools for bacterial engineering. We showed recently that
the transducing bacteriophage phiMAM1 is a ViI-like phage and a member of the new
genus, 'Viunalikevirus'. Here, we show that four additional ViI-like phages and
three new environmentally isolated viunalikeviruses, all infecting plant and
human pathogens, are very efficient generalised transducers capable of
transducing chromosomal markers at frequencies of up to 10(-4) transductants per
plaque-forming unit. We also demonstrate the interstrain transduction of plasmids
and chromosomal markers, including genes involved in anabolism, genes for
virulence and genes encoding secondary metabolites involved in biocontrol. We
propose that all viunalikeviruses are likely to perform efficient horizontal gene
transfer. Viunalikeviruses therefore represent useful agents for functional
genomics and bacterial engineering, and for chemical and synthetic biology
studies, but could be viewed as inappropriate choices for phage therapy.
PMID- 25118077
TI - The quantified patient: a patient participatory culture.
AB - The Quantified Self Movement, which aims to improve various aspects of life and
health through recording and reviewing daily activities and biometrics, is a new
and upcoming practice of self monitoring that holds much promise. Now, the most
underutilized resource in ambulatory health care, the patient, can participate
like never before, and the patient's Quantified Self can be directly monitored
and remotely accessed by health care professionals.
PMID- 25118076
TI - Physical performance and clinical outcomes in dialysis patients: a secondary
analysis of the EXCITE trial.
AB - BACKGROUND/AIMS: Scarce physical activity predicts shorter survival in dialysis
patients. However, the relationship between physical (motor) fitness and clinical
outcomes has never been tested in these patients. METHODS: We tested the
predictive power of an established metric of motor fitness, the Six-Minute
Walking Test (6MWT), for death, cardiovascular events and hospitalization in 296
dialysis patients who took part in the trial EXCITE (ClinicalTrials.gov
Identifier: NCT01255969). RESULTS: During follow up 69 patients died, 90 had
fatal and non-fatal cardiovascular events, 159 were hospitalized and 182 patients
had the composite outcome. In multivariate Cox models - including the study
allocation arm and classical and non-classical risk factors - an increase of 20
walked metres during the 6MWT was associated to a 6% reduction of the risk for
the composite end-point (P=0.001) and a similar relationship existed between the
6MWT, mortality (P<0.001) and hospitalizations (P=0.03). A similar trend was
observed for cardiovascular events but this relationship did not reach
statistical significance (P=0.09). CONCLUSIONS: Poor physical performance
predicts a high risk of mortality, cardiovascular events and hospitalizations in
dialysis patients. Future studies, including phase-2 EXCITE, will assess whether
improving motor fitness may translate into better clinical outcomes in this high
risk population.
PMID- 25118078
TI - Re: Self TH, Patterson SJ, Headley AS, et al. Action plans to reduce
hospitalizations for chronic obstructive pulmonary disease exacerbations: focus
on oral corticosteroids. Curr Med Res Opin 2014;30(12):2607-15.
PMID- 25118079
TI - Mirtazapine associated with drug-related thrombocytopenia: a case report.
PMID- 25118080
TI - Revisiting the "cheese reaction": more than just a hypertensive crisis?
PMID- 25118081
TI - Serpentine tongue syndrome associated with risperidone long-acting injection
treatment.
PMID- 25118082
TI - Risperidone-associated urinary incontinence in patients with autistic disorder
with mental retardation.
AB - We report several cases in which patients with autistic disorder with mental
retardation who received risperidone experienced urinary incontinence. We
retrospectively investigated the medical records of patients housed in facilities
for patients with autistic disorder with mental retardation. Those who had
undergone a medical examination at a hospital in Tokyo from April 1999 to March
2009 were included in the study.Retrospective data were gathered including age,
sex, IQ, birth weight, dosage of risperidone, urinary density, as well as
existence of urinary and fecal incontinence. We divided the participants into
those who did and did not experience urinary incontinence after taking
risperidone and compared the 2 groups. Risperidone had been prescribed to 35
patients. In spite of the fact that no patient had a history of urinary
incontinence, 14 patients experienced urinary incontinence after receiving
risperidone. Moreover, 4 of these 14 patients also had fecal incontinence. Among
the variables we examined, the only significant difference between groups was in
sex, with significantly more women experiencing incontinence compared with men.
When the dose of risperidone was reduced or the patients switched to other drugs,
urinary incontinence of the patients improved.Hence, risperidone may have a
casual relationship with urinary incontinence. Further research is needed to
understand the pathophysiology of possible effect.
PMID- 25118083
TI - Reboxetine adjuvant therapy in patients with schizophrenia showing a suboptimal
response to clozapine: a 12-week, open-label, pilot study.
AB - The present 12-week open-label uncontrolled trial was aimed to explore the
efficacy of reboxetine add-on pharmacotherapy on clinical symptoms and cognitive
functioning in 15 patients with schizophrenia with suboptimal response (mean [SD]
Brief Psychiatric Rating Scale baseline total score, 32.2 [5.4]) despite
receiving clozapine monotherapy at the highest tolerated dosage. The results
obtained evidenced that reboxetine at a dosage of 4 mg/d mildly reduced only
depressive symptoms (Calgary Depression Scale for Schizophrenia: P = 0.035, Cohen
d = 0.7), whereas worsening of performances on phonemic fluency (P = 0.012, Cohen
d = 0.5) was observed. After Bonferroni correction, changes at the Calgary
Depression Scale for Schizophrenia and at the Verbal Fluency Task were not
further confirmed.The results obtained indicate that reboxetine seemed to be
scarcely effective for reducing clinical symptoms in patients with schizophrenia
who have had an incomplete clinical response to clozapine. Regarding cognitive
functioning, in our sample, a trend to experience cognitive impairment in the
examined domains was observed, as confirmed by a mild worsening of performances
on cognitive tasks.Schizophrenia is a heterogeneous disorder with regard to
pathophysiology; therefore, data reflecting the mean response of a sample of
patients may fail to reveal therapeutic effects. More research is needed to
better identify subgroups of patients with peculiar features, which may account
for responsivity to experimental medications and augmentation strategies.
PMID- 25118084
TI - STAR--people-powered prioritization: a 21st-century solution to allocation
headaches.
AB - The aim of cost effectiveness analysis (CEA) is to inform the allocation of
scarce resources. CEA is routinely used in assessing the cost-effectiveness of
specific health technologies by agencies such as the National Institute for
Health and Clinical Excellence (NICE) in England and Wales. But there is
extensive evidence that because of barriers of accessibility and acceptability,
CEA has not been used by local health planners in their annual task of allocating
fixed budgets to a wide range of types of health care. This paper argues that
these planners can use Socio Technical Allocation of Resources (STAR) for that
task. STAR builds on the principles of CEA and the practice of program budgeting
and marginal analysis. STAR uses requisite models to assess the cost
effectiveness of all interventions considered for resource reallocation by
explicitly applying the theory of health economics to evidence of scale, costs,
and benefits, with deliberation facilitated through an interactive social process
of engaging key stakeholders. In that social process, the stakeholders generate
missing estimates of scale, costs, and benefits of the interventions; develop
visual models of their relative cost-effectiveness; and interpret the results. We
demonstrate the feasibility of STAR by showing how it was used by a local health
planning agency of the English National Health Service, the Isle of Wight Primary
Care Trust, to allocate a fixed budget in 2008 and 2009.
PMID- 25118085
TI - Calcium and vitamin D supplementation maintains parathyroid hormone and improves
bone density during initial military training: a randomized, double-blind,
placebo controlled trial.
AB - Calcium and vitamin D are essential nutrients for bone health. Periods of
activity with repetitive mechanical loading, such as military training, may
result in increases in parathyroid hormone (PTH), a key regulator of Ca
metabolism, and may be linked to the development of stress fractures. Previous
studies indicate that consumption of a Ca and vitamin D supplement may reduce
stress fracture risk in female military personnel during initial military
training, but circulating markers of Ca and bone metabolism and measures of bone
density and strength have not been determined. This randomized, double-blind,
placebo-controlled trial sought to determine the effects of providing
supplemental Ca and vitamin D (Ca+Vit D, 2000mg and 1000IU/d, respectively),
delivered as 2 snack bars per day throughout 9weeks of Army initial military
training (or basic combat training, BCT) on PTH, vitamin D status, and measures
of bone density and strength in personnel undergoing BCT, as well as independent
effects of BCT on bone parameters. A total of 156 men and 87 women enrolled in
Army BCT (Fort Sill, OK; 34.7 degrees N latitude) volunteered for this study.
Anthropometric, biochemical, and dietary intake data were collected pre- and post
BCT. In addition, peripheral quantitative computed tomography was utilized to
assess tibia bone density and strength in a subset of volunteers (n=46).
Consumption of supplemental Ca+Vit D increased circulating ionized Ca (group-by
time, P=0.022), maintained PTH (group-by-time, P=0.032), and increased the
osteoprotegerin:RANKL ratio (group-by-time, P=0.006). Consistent with the
biochemical markers, Ca+Vit D improved vBMD (group-by-time, P=0.024) at the 4%
site and cortical BMC (group-by-time, P=0.028) and thickness (group-by-time,
P=0.013) at the 14% site compared to placebo. These data demonstrate the benefit
of supplemental Ca and vitamin D for maintaining bone health during periods of
elevated bone turnover, such as initial military training. This trial was
registered with ClincialTrials.gov, NCT01617109.
PMID- 25118087
TI - Fine particulate matter and risk of preterm birth and pre-labor rupture of
membranes in Perth, Western Australia 1997-2007: a longitudinal study.
AB - OBJECTIVE: A recent longitudinal study reported an association between fine
particulate (PM2.5) exposure and preterm birth (PTB) in a US cohort. We applied
the same design to an Australian cohort to investigate associations with PTB and
pre-labor rupture of membranes (PROM). METHODS: From 287,680 births, we selected
39,189 women who had singleton births at least twice in Western Australia in 1997
2007 (n=86,844 births). Analyses matched pregnancies to the same women with
conditional logistic regression. RESULTS: For PROM adjusted odds ratios (ORs) for
a 1 MUg/m(3) increase in PM2.5 in the first trimester, second trimester, third
trimester, and whole pregnancy were 1.00 (95% confidence interval (CI): 0.97,
1.03), 1.03 (95% CI: 1.00, 1.06), 1.02 (95% CI: 1.00, 1.05), and 1.02 (95% CI:
0.99, 1.05) respectively. For PTB, corresponding ORs were 1.00 (95% CI: 0.96,
1.04), 1.00 (95% CI: 0.96, 1.04), 0.98 (95% CI: 0.94, 1.02), and 0.99 (95% CI:
0.95, 1.04) respectively. CONCLUSION: Risk of PROM was greater for pregnancies
with elevated PM2.5 exposure in the second trimester than were other pregnancies
to the same Australian women at lower exposure. There was insufficient evidence
for an association with PTB, indicating that a longer time period might be needed
to observe an association if a causal effect exists.
PMID- 25118089
TI - Physical activity and renal transplantation.
AB - Renal transplantation is burdened by high cardiovascular risk because of
increased prevalence of traditional and disease-specific cardiovascular risk
factors and, consequently, patients are affected by greater morbidity and
mortality. In renal transplanted patients, healthy lifestyle and physical
activity are recommended to improve overall morbidity and cardiovascular
outcomes. According to METs (Metabolic Equivalent Task; i.e. the amount of energy
consumed while sitting at rest), physical activities are classified as sedentary
(<3.0 METs), of moderate-(3.0 to 5.9 METs) or vigorous-intensity (>= 6.0 METs).
Guidelines suggest for patients with chronic kidney disease an amount of physical
activity of at least 30 minutes of moderate-intensity activity five times per
week (min 450 MET-minutes/week). Data on physical activity in renal transplanted
patients, however, are limited and have been mainly obtained by mean of non
objective methods. Available data suggest that physical activity is low either at
the start or during renal transplantation and this may be associated with poor
patient and graft outcomes. Therefore, in renal transplanted patients more data
on physical activity obtained with objective, accelerometer-based methods are
needed. In the meanwhile, physical activity have to be considered as an essential
part of the medical care for renal transplanted recipients.
PMID- 25118090
TI - Low-alcohol Beers: Flavor Compounds, Defects, and Improvement Strategies.
AB - Beer consumers are accustomed to a product that offers a pleasant and well
defined taste. However, in alcohol-free and alcohol-reduced beers these
characteristics are totally different from those in regular beer. Therefore, it
is important to evaluate and determine the different flavor compounds that affect
organoleptic characteristics to obtain a product that does not contain off
flavors, or taste of grass or wort. The taste defects in alcohol-free beer are
mainly attributed to loss of aromatic esters, insufficient aldehydes, reduction
or loss of different alcohols, and an indeterminate change in any of its
compounds during the dealcoholization process. The dealcoholization processes
that are commonly used to reduce the alcohol content in beer are shown, as well
as the negative consequences of these processes to beer flavor. Possible
strategies to circumvent such negative consequences are suggested.
PMID- 25118088
TI - A PBPK model to estimate PCDD/F levels in adipose tissue: comparison with
experimental values of residents near a hazardous waste incinerator.
AB - This study was aimed at determining the concentrations of polychlorinated dibenzo
p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in 15 samples of adipose
tissue from subjects who had been living in the vicinity of a hazardous waste
incinerator (HWI). The results were compared with levels obtained in previous
surveys carried out in 1998 (baseline study), 2002 and 2007. The current (2013)
concentrations of PCDD/Fs in adipose tissue ranged from 2.8 to 46.3 pg WHO-TEQ/g
fat (mean and median concentrations: 11.5 and 7.4 pg WHO-TEQ/g fat,
respectively), being significantly lower (64%) than those observed in 1998. In
contrast, no significant differences in the mean PCDD/F concentrations were noted
in the period 2002-2013. The significant decrease of the PCDD/F content in fat,
also noted in other biological monitors such as plasma and breast milk, is in
agreement with the reduction in the dietary intake of PCDD/Fs found in the same
area of study. Similarly to other investigations across Europe, an increase of
PCDD/F levels in adipose tissue in relation to age was observed, while no
significant differences were noted according to gender. A multicompartmental
physiologically-based pharmacokinetic (PBPK) model was also applied to estimate
the levels of PCDD/Fs in adipose tissue. When comparing the modeled and
experimental concentrations of PCDD/Fs in that tissue, very similar values were
obtained for the four surveys, which indicates this can be a reliable tool to
predict the internal dose of PCDD/Fs.
PMID- 25118086
TI - Prepubertal organochlorine pesticide concentrations and age of pubertal onset
among Russian boys.
AB - BACKGROUND: In animal studies, organochlorine pesticide (OCP) exposure alters
pubertal development; however, epidemiological data are limited and inconsistent.
OBJECTIVE: To evaluate the associations of serum OCP concentrations
[hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and p,p'
dichlorodiphenyldichloroethylene (p,p'-DDE)] with male pubertal onset. METHODS:
In Chapaevsk, Russia, a town environmentally contaminated with OCPs, 350 8-9 year
old boys with measured OCPs were enrolled during 2003-2005 and were followed
annually for eight years. We evaluated three measures of pubertal onset:
testicular volume (TV)>3 mL in either testis, or stage 2 or greater for genitalia
(G2+), or pubic hair (P2+). We used multivariable interval-censored models to
evaluate associations of OCPs (quartiles) with physician-assessed pubertal onset.
RESULTS: In adjusted models, boys with higher HCB concentrations had later mean
ages of TV>3 mL and P2+ (but not G2+). Mean age at attaining TV>3 mL was delayed
3.6 (95% CI: -2.6, 9.7), 7.9 (95% CI: 1.7, 14.0), and 4.7 months (95% CI: -1.4,
10.9) for HCB Q2, Q3, and Q4, respectively, compared to Q1 (trend p: 0.06). Boys
with higher HCB concentrations reached P2+ 0.1 months earlier (95% CI: -5.8, 5.6)
for Q2, 4.7 months later (95% CI: -1.0, 10.3) for Q3 and 4.6 months later (95%
CI: -1.1, 10.3) for Q4 compared to Q1 (trend p: 0.04). There were no associations
of serum beta-HCH and p,p'-DDE concentrations with age of pubertal onset.
CONCLUSION: Higher prepubertal serum HCB concentrations were associated with
later age of gonadarche and pubarche.
PMID- 25118098
TI - Being both and acting 'man': exploring patterns of masculinisation among young
same-sex-attracted men in Thailand.
AB - Twenty-five same-sex-attracted rural young Thai men were interviewed three times
to investigate how their sexual subjectivity changed over an 18-month period
after they completed high school and moved into a new life-phase. Many young men
grew up with strong gender-based understandings of homosexuality, in which a
masculine (top) partner is seen as complementing a feminine (bottom) partner. The
discursive division between the masculine and feminine domains became
increasingly blurred in the actual practice of dating, forcing the young men to
develop new understandings of homosexuality and same-sex relations. The shift
from a rural to urban environment, the use of the Internet and the experience of
falling in love played important roles in this experimentation with new,
increasingly masculine presentations of the self, also influenced by a modern
urban masculine aesthetic. The paper concludes that the encounter between
'traditional' gender-based homosexuality and new ideas, in which masculine object
choice is important in defining sexual identity leads to a variety of fluid ideas
and expressions. This process created confusion among some, and opportunities for
exploration of new ways of defining sexual subjectivities among others.
PMID- 25118091
TI - Effect evaluation of two types of dementia-specific case conferences in German
nursing homes (FallDem) using a stepped-wedge design: study protocol for a
randomized controlled trial.
AB - BACKGROUND: Case conferences for people with dementia and challenging behaviors
(e.g., apathy) are recommended as useful tools that enable staff in nursing homes
to understand the behavior of people with this type of disease. Understanding
peoples' behaviors is the basis for the initiation of targeted interventions to
improve the quality of care for people with dementia. Furthermore, case
conferences demonstrate positive effects on burnout, dementia-specific burden,
and vocational action competence of the staff. The two likely approaches for
conducting case conferences include the following: A) using a structured
assessment instrument, which guides the staff in understanding the residents'
behaviors and B) using a narrative approach in which the staff must identify the
reasons for the residents' behaviors in an unstructured manner. Case conferences
are a complex intervention, and evaluating their multiple effects is challenging.
The aim of this study protocol was to describe a likely solution for evaluating
this type of complex intervention using a special cluster randomized trial.
METHODS: In this stepped-wedged cluster randomized trial, the two interventions
will be sequentially implemented every three months in a group of 12 nursing
homes (clusters) with a minimum of 360 residents over 19 months (7 months of
intervention for each cluster and follow-up). The primary outcome is the
reduction of challenging behavior (measured with the neuropsychiatric inventory
nursing home version [NPI-NH]). Secondary outcomes are residents' quality of
life, prescription of psychotropic medications, staff burnout, dementia-related
stress, and vocational action competence. The effectiveness of the study will be
accompanied by a process evaluation. The primary data will be analyzed using a
Bayesian mixed effect model; the secondary data will be analyzed using
descriptive statistics and mixed effects models. DISCUSSION: The implementation
and effect measurement of complex interventions such as case conferences within a
cluster randomized trial are challenging (e.g., complex and intensive training,
delayed treatment effect). In this study protocol, the methodological advantages
and disadvantages of using the stepped wedge design to answer the research
questions are discussed. TRIAL REGISTRATION: http://www.controlled
trials.com/ISRCTN20203855; registered 10 July 2013.
PMID- 25118092
TI - Myocyte growth, repair, and oxidative stress following pediatric heart
transplantation.
AB - Cardiac remodeling is associated with plasma biomarkers of fibrinogenesis,
inflammation, and oxidative stress, and upregulation of mitogenic, pro-fibrotic,
and apoptotic signaling pathways. Our primary objective was to evaluate biomarker
and subcellular myocardial changes in pediatric heart transplant recipients.
Fifty-two-week prospective, randomized (tacrolimus, Tac, vs. cyclosporine, CsA),
open-label, parallel group study. Serial myocardial biopsies were probed for
mitogenic and pro-inflammatory proteins. Plasma biomarkers of oxidative stress
(F2alpha isoprostanes, nitrotyrosine), and inflammation and oxidation (hsCRP and
cystatin-C) were measured. Nine of 11 randomized patients completed the study
(four Tac, five CsA). Mean levels of F2alpha isoprostanes, hsCRP, and cystatin-C
were maximal at Week 2. Peak activation of all MAP kinases in myocardial tissue
was maximal at Week 10; no association was seen with rejection. Cardiac Bax/Bcl-2
levels (index of apoptosis) correlated negatively with F2alpha isoprostanes at
Week 2 (r = -0.88) and with hsCRP at Week 52 (r = -0.67). At Week 52, hsCRP
levels correlated positively with molecular indices of cardiac cell growth. We
found evidence of systemic and myocardial oxidative damage and inflammation early
posttransplant, which may be related to the remodeling process. Further study is
needed to better understand the cardiac and systemic repair processes following
pediatric heart transplantation.
PMID- 25118100
TI - Molecular phylogeny of Asian Meconopsis based on nuclear ribosomal and
chloroplast DNA sequence data.
AB - The taxonomy and phylogeny of Asian Meconopsis (Himalayan blue poppy) remain
largely unresolved. We used the internal transcribed spacer (ITS) region of
nuclear ribosomal DNA (nrDNA) and the chloroplast DNA (cpDNA) trnL-F region for
phylogenetic reconstruction of Meconopsis and its close relatives Papaver,
Roemeria, and Stylomecon. We identified five main clades, which were well
supported in the gene trees reconstructed with the nrDNA ITS and cpDNA trnL-F
sequences. We found that 41 species of Asian Meconopsis did not constitute a
monophyletic clade, but formed two solid clades (I and V) separated in the
phylogenetic tree by three clades (II, III and IV) of Papaver and its allies.
Clade V includes only four Asian Meconopsis species, with the remaining 90
percent of Asian species included in clade I. In this core Asian Meconopsis
clade, five subclades (Ia-Ie) were recognized in the nrDNA ITS tree. Three
species (Meconopsis discigera, M. pinnatifolia, and M. torquata) of subgenus
Discogyne were imbedded in subclade Ia, indicating that the present definition of
subgenera in Meconopsis should be rejected. These subclades are inconsistent with
any series or sections of the present classifications, suggesting that
classifications of the genus should be completely revised. Finally, proposals for
further revision of the genus Meconopsis were put forward based on molecular,
morphological, and biogeographical evidences.
PMID- 25118099
TI - The rise of mortality from mental and neurological diseases in Europe, 1979-2009:
observational study.
AB - BACKGROUND: We studied recent trends in mortality from seven mental and
neurological conditions and their determinants in 41 European countries. METHODS:
Age-standardized mortality rates were analysed using standard methods of
descriptive epidemiology, and were related to cultural, economic and health care
indicators using regression analysis. RESULTS: Rising mortality from mental and
neurological conditions is seen in most European countries, and is mainly due to
rising mortality from dementias. Mortality from psychoactive substance use and
Parkinson's disease has also risen in several countries. Mortality from dementias
has risen particularly strongly in Finland, Iceland, Malta, Netherlands, Spain,
Sweden and the United Kingdom, and is positively associated with self-expression
values, average income, health care expenditure and life expectancy, but only the
first has an independent effect. CONCLUSIONS: Although trends in mortality from
dementias have probably been affected by changes in cause-of-death
classification, the high level of mortality from these conditions in a number of
vanguard countries suggests that it is now among the most frequent causes of
death in high-income countries. Recognition of dementias as a cause of death,
and/or refraining from life-saving treatment for patients with dementia, appear
to be strongly dependent on cultural values.
PMID- 25118102
TI - Growing the seeds sown by Piero Sensi.
AB - Piero Sensi is probably known primarily for his role in the discovery of
rifamycin and for developing it to be a drug of fundamental importance in the
treatment of tuberculosis. He has also contributed to promote screening programs
of microbial products and research approaches for antibacterial agents that have
been further developed up to the present day. This paper reports a sequence of
discovery approaches, failures and successes that spans for about 50 years and is
still in progress.
PMID- 25118101
TI - Follicle stimulating hormone receptor in mesenchymal stem cells integrates
effects of glycoprotein reproductive hormones.
AB - Previously we reported that follicle stimulating hormone (FSH) affects bone
degradation in human cells and in follicle stimulating hormone receptor (FSH-R)
null mice. Here we describe a FSH-R knockout bone-formation phenotype. We used
mesenchymal stem cells (MSCs), osteoblast precursors that express FSH-R, to
determine whether FSH regulates bone formation. FSH stimulates MSC cell adhesion
1-3 h and proliferation at 24 h after addition. On the basis of phylogenetic and
clinical precedents, we also examined effects of pregnant levels of human
chorionic gonadotropin (hCG) on MSCs. We found effects similar to those of FSH,
and RNAi knockdown of FSH-R abrogated both FSH and hCG effects on MSCs. In
contrast to effects on MSCs, neither FSH nor hCG had significant effects on
osteoblast maturation. Also in MSCs, short-term treatment by FSH and hCG altered
signaling pathways for proliferation, including Erk1/2 phosphorylation. Our
results show augmentation of MSC proliferation by either FSH at menopausal levels
or hCG at normal pregnant levels. We conclude that FSH-R participates in
regulation of MSC precursor pools in response to either FSH or hCG, integrating
the effects of these two glycoprotein hormones.
PMID- 25118103
TI - Resistance to rifampicin: a review.
AB - Resistance to rifampicin (RIF) is a broad subject covering not just the mechanism
of clinical resistance, nearly always due to a genetic change in the beta subunit
of bacterial RNA polymerase (RNAP), but also how studies of resistant polymerases
have helped us understand the structure of the enzyme, the intricacies of the
transcription process and its role in complex physiological pathways. This review
can only scratch the surface of these phenomena. The identification, in strains
of Escherichia coli, of the positions within beta of the mutations determining
resistance is discussed in some detail, as are mutations in organisms that are
therapeutic targets of RIF, in particular Mycobacterium tuberculosis.
Interestingly, changes in the same three codons of the consensus sequence occur
repeatedly in unrelated RIF-resistant (RIF(r)) clinical isolates of several
different bacterial species, and a single mutation predominates in mycobacteria.
The utilization of our knowledge of these mutations to develop rapid screening
tests for detecting resistance is briefly discussed. Cross-resistance among
rifamycins has been a topic of controversy; current thinking is that there is no
difference in the susceptibility of RNAP mutants to RIF, rifapentine and
rifabutin. Also summarized are intrinsic RIF resistance and other resistance
mechanisms.
PMID- 25118105
TI - Glycopeptide antibiotics: back to the future.
AB - Glycopeptide antibiotics have been a key weapon in the fight against bacterial
infections for over half a century, with the progenitors, vancomycin (1) and
teicoplanin (2), still used extensively. The increased occurrence of resistance
and the effectiveness of these 'last resort' treatments for Gram-positive
infections has led to the discovery and clinical development of second
generation, semisynthetic lipoglycopeptide derivatives such as telavancin (3),
dalbavancin (4) and oritavancin (5), which all possess broader spectra of
activity and improved pharmacokinetic properties. Two of these new antibiotics,
telavancin (3) and dalbavancin (4), were approved in the past 5 years and the
third, oritavancin (5), is awaiting regulatory approval. In this review, the
discovery, development and associated resistance of vancomycin (1) and
teicoplanin (2), and semi-synthetic glycopeptides, telavancin (3), dalbavancin
(4) and oritavancin (5), are detailed. The clinical implications of glycopeptide
resistance, especially vancomycin (1), as well as the future prospects for
current glycopeptide drugs and the development of new glycopeptides are
discussed.
PMID- 25118104
TI - Sesquiterpenoids and xanthones derivatives produced by sponge-derived fungus
Stachybotry sp. HH1 ZSDS1F1-2.
AB - A new (2) and four known (1, 8-10) sesquiterpenoids, two new (3 and 4) and eight
known (5-7, 11-15) xanthone derivatives were isolated from the cultures of sponge
derived fungus Stachybotry sp. HH1 ZDDS1F1-2. The structure of the compounds 1-15
was determined mainly by analysis of the one-dimensional and two-dimensional NMR
spectroscopic data and by analogy with the data of those reported. Compound 1 was
confirmed by X-ray crystallography. All the compounds were tested for their
cytotoxic, antiinflammatory and antiviral (EV71) effects. Compounds 5, 7 and 11
showed significant cytotoxicity against selected human tumor cell lines.
Compounds 3, 4 and 11 also displayed significant inhibitory activity against
cycloooxygenase (COX-2). Compounds 4, 5 and 11 showed activities against
intestinal virus EV71.
PMID- 25118106
TI - New bicyclic hemiacetals from the edible mushroom Ramaria madagascariensis.
PMID- 25118108
TI - Spontaneous and induced mutations to rifampicin, streptomycin and spectinomycin
resistances in actinomycetes: mutagenic mechanisms and applications for strain
improvement.
AB - Chemical mutagenesis continues to be an important foundational methodology for
the generation of highly productive actinomycete strains for the commercial
production of antibiotics and other secondary metabolites. In the past, the
determination of frequencies of chemically induced resistance to rifampicin
(RifR), spectinomycin (SpcR) and streptomycin (StrR) have served as surrogate
markers to monitor the efficiencies and robustness of mutagenic protocols. Recent
studies indicate that high level RifR, SpcR and StrR phenotypes map to specific
regions of the rpoB, rpsE and rpsL genes, respectively, in actinomycetes.
Moreover, mutagenesis to RifR can occur spontaneously at many different sites in
rpoB, and all six types of base-pair substitutions, as well as in-frame deletions
and insertions, have been observed. The RifR/rpoB system provides a robust method
to rank mutagenic protocols, to evaluate mutagen specificity and to study
spontaneous mutagenesis mechanisms involved in the maintenance of high G+C
content in Streptomyces species and other actinomycetes.
PMID- 25118107
TI - Allantopyrone A, an alpha-pyrone metabolite from an endophytic fungus, inhibits
the tumor necrosis factor alpha-induced nuclear factor kappaB signaling pathway.
AB - Tumor necrosis factor alpha (TNF-alpha) induces the activation of transcription
factor nuclear factor kappaB (NF-kappaB), which upregulates a variety of genes,
including the gene encoding intercellular adhesion molecule-1 (ICAM-1).
Allantopyrone A, a recently identified alpha-pyrone metabolite from an endophytic
fungus, was found to inhibit the TNF-alpha-induced expression of ICAM-1 in human
lung carcinoma A549 cells. Allantopyrone A also inhibited the TNF-alpha-induced
luciferase expression of an NF-kappaB-responsive reporter. In the NF-kappaB
signaling pathway, allantopyrone A inhibited the nuclear translocation of NF
kappaB subunits as well as the phosphorylation and subsequent degradation of the
inhibitor of NF-kappaB (IkappaB) alpha proteins. By contrast, allantopyrone A did
not directly affect the catalytic activity of active IkappaB kinase beta. These
findings indicate that allantopyrone A inhibits the NF-kappaB signaling pathway
at a step upstream of IkappaBalpha phosphorylation.
PMID- 25118109
TI - Characterization of swine leukocyte antigen alleles and haplotypes on a novel
miniature pig line, Microminipig.
AB - Microminipigs are extremely small-sized, novel miniature pigs that were recently
developed for medical research. The inbred Microminipigs with defined swine
leukocyte antigen (SLA) haplotypes are expected to be useful for allo- and
xenotransplantation studies and also for association analyses between SLA
haplotypes and immunological traits. To establish SLA-defined Microminipig lines,
we characterized the polymorphic SLA alleles for three class I (SLA-1, SLA-2 and
SLA-3) and two class II (SLA-DRB1 and SLA-DQB1) genes of 14 parental
Microminipigs using a high-resolution nucleotide sequence-based typing method.
Eleven class I and II haplotypes, including three recombinant haplotypes, were
found in the offspring of the parental Microminipigs. Two class I and class II
haplotypes, Hp-31.0 (SLA-1*1502-SLA-3*070102-SLA-2*1601) and Hp-0.37 (SLA
DRB1*0701-SLA-DQB1*0502), are novel and have not so far been reported in other
pig breeds. Crossover regions were defined by the analysis of 22 microsatellite
markers within the SLA class III region of three recombinant haplotypes. The SLA
allele and haplotype information of Microminipigs in this study will be useful to
establish SLA homozygous lines including three recombinants for transplantation
and immunological studies.
PMID- 25118110
TI - Development of bead-based suspension array technology for the diagnosis of
thalassemia.
PMID- 25118111
TI - A TdT-mediated cascade signal amplification strategy based on dendritic DNA
matrix for label-free multifunctional electrochemical biosensing.
AB - We describe a novel label-free amplified multifunctional strategy of dendritic
electrochemical DNA sensor based on terminal deoxynucleotidyl transferase (TdT).
We have found that the sequence composition of TdT-yielded DNA is largely
dependent on the constitution of substrate deoxynucleotides (dNTPs) pool. After
rational design of dNTPs pool and controllable TdT polymerization, dendritic
protocol has been developed involving two-type amplification strategies; one is
the formation of "trunk" and "branch" of the dendritic electrochemical sensor by
TdT amplification; the other is the introduction of nucleic acid functionalized
Au nanoparticles (DNA-AuNPs) for multiple branching. The results indicate that
the G-rich ssDNA, which is synthesized under the condition of 40% deoxyadenosine
triphosphate (dATP) and 60% deoxyguanosine triphosphate (dGTP), can be induced to
form a long signal strand to G-quadruples (G4) in the presence of Pb(2+). The
electrochemical sensing platform is employed for sequence-specific DNA detection
and the detection limit is as low as 1 fM. Our multifunctional strategy is
further extended to Pb(2+) detection and thrombin aptasensor. This proposed
sensor displays excellent sensitivity and selectivity, and is applied for
detection in complicated samples successfully.
PMID- 25118112
TI - Physical activity in solid organ transplant recipients: preliminary results of
the Italian project.
AB - BACKGROUND/AIMS: The role of physical activity in transplanted patients is often
underestimated. We discuss the Italian National Transplant Centre experience,
which started in 2008 studying transplanted patients involved in sports
activities. The study was then developed through a model of cooperation between
surgeons, sports physicians and exercise specialists. METHODS: A multicentre
study was realized in 120 transplanted patients of which 60 treated with
supervised physical activity (three sessions/week of aerobic and strengthening
exercises) and 60 controls. We present the results of the first 26 patients (16
males, 10 females; 47.8 +/- 10.0 years; 21 kidney, 5 liver transplanted; time
from transplant 2.3 +/- 1.4 years) who completed 12 months of supervised physical
activity. RESULTS: Data showed an increase of peak aerobic power (t=4.535;
P<0.01) and maximum workload (t=4.665; P<0.01) in the incremental cycling test.
Maximum strength of knee extensors (t=2.933; P<0.05) and elbow flexors (t=2.450;
P<0.05), and the power of lower limb (t=2.303; P<0.05) significantly increases.
Health Related Quality of Life showed a significant improvement. Serum creatinine
(1.4 +/- 0.5 vs 1.3 +/- 0.4 mg/dL) and proteinuria (0.10 +/- 0.14 vs 0.08 +/-
0.08 gr/dL) were stable. CONCLUSION: These preliminary results confirm the
positive effects of supervised physical exercise. It can be considered as an
input to promote other detailed exercise protocols.
PMID- 25118113
TI - Application of Glass Transition in Food Processing.
AB - The phenomenon of glass transition has been employed to food products to study
their stability. It can be applied as an integrated approach along with water
activity and physical and chemical changes in food in processing and storage to
determine the food stability. Also associated with the changes during
agglomeration crystallization, caking, sticking, collapse, oxidation reactions,
nonenzymatic browning, and microbial stability of food system. Various techniques
such as Differential Scanning Calorimetry, Nuclear Magnetic Resonance, etc. have
been developed to determine the glass transition temperature (Tg) of food system.
Also, various theories have been applied to explain the concept of Tg and its
relation to changes in food system. This review summarizes the understanding of
concept of glass transition, its measurement, and application in food technology.
PMID- 25118115
TI - Relationship between serum leptin and chronic obstructive pulmonary disease in US
adults: results from the third National Health and Nutrition Examination Survey.
AB - BACKGROUND: Recent studies suggest an important role for leptin in respiratory
immune responses and pathogenesis of inflammatory respiratory diseases. There has
been an interest to explore whether leptin plays any role in the pathogenesis of
chronic obstructive pulmonary disease (COPD). OBJECTIVE: We conducted a
population-based study to evaluate the relationship between serum leptin and COPD
in the third US National Health and Nutrition Examination Survey participants.
PARTICIPANTS AND DESIGN: Our study group was constituted by 6415 adults who had
fasting serum leptin and underwent spirometry measurement. MAIN OUTCOME MEASURES:
Serum leptin levels were compared (1) between subjects with normal lung function
and those with COPD and (2) among COPD subjects with different severities.
RESULTS: Among male participants, 2257 were controls, and 680 had COPD. Compared
with controls, COPD subjects were older (62 vs 43 years) and had higher
prevalence of smokers (78% vs 58%), lower body mass index (BMI) (26.3 vs 26.9),
and higher serum leptin levels (6.6 vs 5.9). For female participants, 2918 were
controls, and 560 had COPD. Those with COPD were older (60 vs 43 years) and had
lower BMI (26.9 vs 27.7). No differences in serum leptin levels were observed.
The independent predictors of COPD in both sexes were age, BMI, and smoking, but
not serum leptin. There were no differences in serum leptin among COPD subjects
with different severities. CONCLUSIONS: We did not find any significant
difference in the levels of serum leptin in subjects with COPD. Our data provide
indirect evidence against a major role for serum leptin in the pathogenesis of
COPD in humans.
PMID- 25118114
TI - Cell-type-specific aptamer and aptamer-small interfering RNA conjugates for
targeted human immunodeficiency virus type 1 therapy.
AB - Human immunodeficiency virus (HIV) is a virus that causes acquired
immunodeficiency syndrome, a chronic and incurable disease of the human immune
system. As the standard of care for the patients with HIV-1, current highly
active antiretroviral treatment has been therapeutically effective in most
patients; however, it is not curative, and highly active antiretroviral treatment
is intolerable because of severe adverse effects. Therefore, nucleic acid-based
therapeutics, such as antisense oligonucleotide, ribozyme, messenger RNA, RNA
interference (RNAi)-based therapeutics, aptamer, and so on, have been actively
developed as alternative or adjuvant agents for those chemical antiviral drugs to
surmount those drawbacks. The combinatorial use of various antiviral nucleic
acids could be more efficacious in blocking viral replication and preventing the
emergence of resistant variants. In this regard, RNAi can function as a gene
specific therapeutic option for controlling HIV-1 replication. Another type of
therapeutic nucleic acid--aptamers--shows promise as a new and potent class of
anti-HIV agent and can additionally function as a cell-type-specific delivery
vehicle for targeted RNAi. The combined use of small interfering RNA (siRNAs) and
aptamers could effectively block viral replication and prevent the emergence of
resistant variants. The present review offers a brief overview of the use of cell
type-specific aptamer and aptamer-siRNA conjugates' development in our group for
the treatment of HIV-1. Their potentials for targeted delivering RNAi
therapeutics (eg, siRNA) and suppressing HIV-1 replication in vitro and in
humanized animal model will be highlighted here.
PMID- 25118116
TI - Comparison of low versus high (>40 mm Hg) pulse pressure to predict the benefit
of cardiac resynchronization therapy for heart failure (from the Multicenter
Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy
Trial).
AB - Low pulse pressure (PP) is associated with poor outcome in hospitalized patients
with systolic heart failure (HF). However, the relation between PP and response
to cardiac resynchronization therapy with defibrillator (CRT-D) is unknown. We
aimed to evaluate the relation between preimplantation PP and echocardiographic
response to CRT-D and subsequent clinical outcome after 1 year. The relation
between preimplantation PP and echocardiographic response to CRT-D (defined as
>15% reduction in left ventricular (LV) end-systolic volume at 1 year) was
evaluated in 754 patients with CRT-D with left bundle branch block enrolled in
Multicenter Automatic Defibrillator Cardioverter Defibrillator Implantation Trial
Cardiac Resynchronization Therapy. The association between PP at 1 year and the
risk for subsequent HF or death was evaluated using multivariate Cox model.
Patients with high versus low PP (>40 vs <=40 mm Hg [lower quartile]) had a
significantly greater reduction in LV end-systolic volume, LV end-diastolic
volume, and LV dyssynchrony (p<0.01 for all comparisons). In multivariate
analysis, the presence of high PP was associated with a 3.5-fold (p<0.001)
increase in the likelihood of a positive echocardiographic response to CRT-D.
Patients with high PP (>40 mm Hg, >lower quartile) 1 year after CRT-D
implantation experienced a 50% reduction in the risk of subsequent HF or death
(p=0.001) and 63% reduction in death only (p=0.001), compared with patients with
low PP. In conclusion, high baseline PP is an independent predictor of
echocardiographic response to CRT-D, and high PP after device implantation is
associated with improved subsequent clinical outcome.
PMID- 25118117
TI - Association of platelet-to-lymphocyte ratio with severity and complexity of
coronary artery disease in patients with acute coronary syndromes.
AB - The SYNTAX score (SXscore) is an anatomic scoring system based on coronary
angiography (CA) that not only quantifies lesion severity and complexity but also
predicts poor cardiovascular outcomes, including mortality, in patients with
acute coronary syndromes (ACS). Recent studies have shown that platelet-to
lymphocyte ratio (PLR) is associated with worse outcomes in many cardiovascular
diseases. The aim of this study was to investigate the association of PLR with
the severity and complexity of coronary atherosclerosis as assessed by the
SXscore in patients with ACS who underwent urgent CA. A total of 1,016 patients
with ACS who underwent urgent CA were included in the study from August 2012 to
March 2014. Admission PLR values were calculated before CA was performed. The
SXscore was determined from baseline CA. The patients were divided into 2 groups,
those with low SXscores (<=22) and those with intermediate to high SXscores
(>=23). PLRs were significantly higher in patients with intermediate to high
SXscores compared with those with low SXscores (p<0.001). In-hospital mortality
was significantly higher in the groups with high PLR and intermediate to high
SXscores. In multivariate analysis, the independent predictors of intermediate to
high SXscore were PLR (odds ratio 1.018, 95% confidence interval 1.013 to 1.023,
p<0.001) together with the left ventricular ejection fraction (odds ratio 0.935,
95% confidence interval 0.910 to 0.960, p<0.001), and age (odds ratio 1.029, 95%
confidence interval 1.029 to 1.054, p=0.02). A PLR>=116 had 71% sensitivity and
66% specificity in predicting intermediate to high SXscore. In conclusion, the
PLR at admission is significantly associated with the severity and complexity of
coronary atherosclerosis in patients with ACS. Increased PLR is an independent
predictor of higher SXscore in patients with ACS who undergo urgent CA.
PMID- 25118118
TI - Predictors of neurologic outcome in patients resuscitated from out-of-hospital
cardiac arrest using classification and regression tree analysis.
AB - The estimated survival rate of 8% to 10% after out-of-hospital cardiac arrest
(OHCA) remains dismal. Few studies have addressed predictors of functional
neurologic outcome after successful resuscitation. The objective of the study was
to identify variables associated with favorable neurologic outcomes, defined by a
Glasgow Coma Scale of 14 or 15, after OHCA. We used a propensity analysis and
classification and regression tree model of 184 OHCA patients surviving to
hospital admission at a cardiac arrest receiving center in Los Angeles County
from 2008 to 2013. Forty-three patients (23%) had a favorable outcome, median age
was 65 years (interquartile range [IQR] 54 to 76), and 98 (53%) were men. Sixty
six patients (36%) presented with a shockable rhythm. The majority were
witnessed, either by a civilian (n=115, 63%) or a paramedic (n=25, 14%).
Bystander cardiopulmonary resuscitation was performed on 84 patients (46%);
median dose of epinephrine was 2 mg (IQR 1 to 3). Median time to return of
spontaneous circulation was 21 minutes (IQR 16 to 29); the median lactate level
was 5.2 mmol/L (IQR 2.8 to 9.2). Lower epinephrine doses (<1.5 mg) and lactate
levels<5 mmol/L were predictive of a normal Glasgow Coma Scale, with 90.7%
sensitivity (95% confidence interval [CI] 76.9% to 96.9%), 47.5% specificity (95%
CI 39.1% to 56.1%), a positive predictive value of 34.5% (95% CI 31.6% to 46.1%),
a negative predictive value of 94.4% (95% CI 85.5% to 98.2%), and an area under
the curve of 0.89. The propensity score-adjusted logistic regression model
demonstrated that receiving <1.5 mg of epinephrine was associated with a
favorable neurologic outcome (odds ratio 3.3, 95% CI 1.1 to 10, p=0.04). In
conclusion, for patients surviving to hospital admission, a good neurologic
outcome was associated with having received <1.5 mg of epinephrine and a lactate
level<5 mmol/L.
PMID- 25118119
TI - Comparison of the efficacy of pharmacoinvasive management for ST-segment
elevation myocardial infarction in smokers versus non-smokers (from the Trial of
Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in
Acute Myocardial Infarction).
AB - Compared with non-smokers, cigarette smokers with ST-segment elevation myocardial
infarctions derive greater benefit from fibrinolytic therapy. However, it is not
known whether the optimal treatment strategy after fibrinolysis differs on the
basis of smoking status. The Trial of Routine Angioplasty and Stenting After
Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI)
randomized patients with ST-segment elevation myocardial infarctions to a routine
early invasive (pharmacoinvasive) versus a standard (early transfer only for
rescue percutaneous coronary intervention or delayed angiography) strategy after
fibrinolysis. The efficacy of these strategies was compared in 1,051 patients on
the basis of their smoking status. Treatment heterogeneity was assessed between
smokers and non-smokers, and multivariable analysis was performed to evaluate for
an interaction between smoking status and treatment strategy after adjusting for
baseline Global Registry of Acute Coronary Events (GRACE) risk score. Smokers
(n=448) were younger, had fewer cardiovascular risk factors, and had lower GRACE
risk scores. They had a lower rate of the primary composite end point of 30-day
mortality, reinfarction, recurrent ischemia, heart failure, or cardiogenic shock
and fewer deaths or reinfarctions at 6 months and 1 year. Smoking status was not
a significant predictor of either primary or secondary end points in
multivariable analysis. Pharmacoinvasive management reduced the primary end point
compared with standard therapy in smokers (7.7% vs 13.6%, p=0.04) and non-smokers
(13.1% vs 19.7%, p=0.03). Smoking status did not modify treatment effect on any
measured outcomes (p>0.10 for all). In conclusion, compared with non-smokers,
current smokers receiving either standard or early invasive management of ST
segment elevation myocardial infarction after fibrinolysis have more favorable
outcomes, which is likely attributable to their better baseline risk profile. The
beneficial treatment effect of a pharmacoinvasive strategy is consistent in
smokers and non-smokers.
PMID- 25118120
TI - Treatment and outcomes of ST segment elevation myocardial infarction and out-of
hospital cardiac arrest in a regionalized system of care based on presence or
absence of initial shockable cardiac arrest rhythm.
AB - The aim of this study was to evaluate the treatment and outcomes of patients with
ST-segment elevation myocardial infarctions complicated by out-of-hospital
cardiac arrest in a regional system of care. In this retrospective study, the
effect of the absence of an initial shockable arrest rhythm was analyzed. The
primary end point of survival with good neurologic outcome in patients with and
without an initial shockable arrest rhythm was adjusted for age, witnessed
arrest, bystander cardiopulmonary resuscitation, and treatment with therapeutic
hypothermia and percutaneous coronary intervention. One-hundred sixty-eight of
348 patients (49%) survived to hospital discharge. Patients with a shockable
initial rhythm were more likely to receive therapeutic hypothermia (48% vs 37%,
risk ratio 1.2, 95% confidence interval [CI] 1.0 to 1.5) and to be treated in the
cardiac catheterization laboratory (80% vs 43%, risk ratio 2.8, 95% CI 2.0 to
3.8). The likelihood of survival with good neurologic outcome in patients with a
shockable initial rhythm compared with those presenting without a shockable
rhythm was 4.8 (95% CI 2.7 to 8.7). In patients who underwent percutaneous
coronary intervention, the likelihood of survival with good neurologic outcome
was higher (risk ratio 2.7, 95% CI 1.1 to 6.8) in those with a shockable rhythm.
In conclusion, the absence of an initial shockable rhythm in patients with ST
segment elevation myocardial infarctions plus out-of-hospital cardiac arrest is
associated with significantly worse survival and neurologic outcome. These
differences persist despite application of therapies including therapeutic
hypothermia and percutaneous coronary intervention within a regionalized system
of care.
PMID- 25118121
TI - Impact of pre-procedural cardiopulmonary instability in patients with acute
myocardial infarction undergoing primary percutaneous coronary intervention (from
the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial
Infarction Trial).
AB - Rapid reperfusion with primary percutaneous coronary intervention improves
survival in patients with ST-segment elevation myocardial infarction.
Preprocedural cardiopulmonary instability and adverse events (IAE) may delay
reperfusion time and worsen prognosis. The aim of this study was to evaluate the
relation between preprocedural cardiopulmonary IAE, door-to-balloon time (DBT),
and outcomes in the Harmonizing Outcomes With Revascularization and Stents in AMI
(HORIZONS-AMI) trial. Preprocedural cardiopulmonary IAE included sustained
ventricular or supraventricular tachycardia or fibrillation requiring
cardioversion or defibrillation, heart block or bradycardia requiring pacemaker
implantation, severe hypotension requiring vasopressors or intra-aortic balloon
counterpulsation, respiratory failure requiring mechanical ventilation, and
cardiopulmonary resuscitation. Three-year outcomes of patients with and without
IAE according to DBT were compared. Among 3,602 patients, 159 (4.4%) had >=1 IAE.
DBT did not differ significantly in patients with and without IAE; however,
patients with IAE were less likely to have Thrombolysis In Myocardial Infarction
(TIMI) grade 3 flow after percutaneous coronary intervention. Mortality at 3
years was significantly higher in patients with versus those without IAE (17.0%
vs 6.3%, p<0.0001), and IAE was an independent predictor of mortality, whereas
DBT was not. However, a significant interaction was present such that 3-year
mortality was reduced in patients with DBT<99 minutes (the median) versus >=99
minutes to a greater extent in patients with IAE (9.9% vs 20.7%, hazard ratio
0.43, 95% confidence interval 0.16 to 1.16) compared with those without IAE (5.0%
vs 7.2%, hazard ratio 0.69, 95% confidence interval 0.50 to 0.95) (p for
interaction=0.004). In conclusion, IAE before PCI is an independent predictor of
death and identifies a high-risk group in whom faster reperfusion may be
particularly important to improve survival.
PMID- 25118122
TI - Meta-analysis of left ventricular hypertrophy and sustained arrhythmias.
AB - Presence of left ventricular hypertrophy (LVH) has been reported to be associated
with supraventricular and ventricular arrhythmias, but the association has not
been systematically quantified and evaluated. A systematic search of studies in
MEDLINE, EMBASE, CINAHL, Scopus, Web of Science, and Cochrane Central Register of
Controlled Trials databases was undertaken through April 2014. Studies reporting
on LVH and sustained arrhythmias such as atrial fibrillation and supraventricular
tachycardias (SVTs) and ventricular arrhythmias (tachycardia and fibrillation)
were identified. Pooled effect estimates were calculated with random-effects
models (DerSimonian and Laird). A total of 10 eligible studies with 27,141
patients were included in the analysis. The incidence of SVT in patients with LVH
was 11.1% compared with 1.1% among patients without LVH (p<0.001). Patients with
LVH had 3.4-fold greater odds of developing SVT (odds ratio 3.39, 95% confidence
interval 1.57 to 7.31) than those without LVH, although significant heterogeneity
was present (I2=98%). Meta-regression analyses revealed the heterogeneity to have
originated from differences in the baseline covariates such as age, male gender,
hypertension, and diabetes of the individual studies. The incidence of
ventricular arrhythmias was 5.5% compared with 1.2% in patients without LVH
(p<0.001). The occurrence of ventricular tachycardia or fibrillation was 2.8-fold
greater, in the presence of LVH (odds ratio 2.83, 95% confidence interval 1.78 to
4.51), and there was no significant heterogeneity (I2=9%). Presence of LVH in
hypertensive patients is associated with a greater risk of sustained
supraventricular/atrial and ventricular arrhythmias, and there is an unmet need
for identifying and refining risk stratification for this group.
PMID- 25118123
TI - Outcomes of patients with ischemic mitral regurgitation undergoing percutaneous
coronary intervention.
AB - Ischemic mitral regurgitation (IMR) is associated with poor outcomes in patients
with coronary artery disease. The impact of percutaneous coronary intervention
(PCI) on patients with IMR is not well elucidated. We sought to determine the
outcomes of patients with severe IMR who underwent PCI. Patients with severe
(>=3+) IMR who underwent PCI from 1998 to 2010 were identified. Improvement in
IMR was defined as reduction in severity from >=3+ to <=2+ without any other
invasive intervention beyond PCI. Outcomes were compared between patients with
and without improvement in IMR after PCI. One hundred thirty-seven patients with
severe IMR were included in our study. After PCI, 50 patients (36.5%) had
improvement in IMR with PCI alone and 24 patients (18.5%) required another
intervention. Left atrial size was a significant predictor of improvement in IMR
(odds ratio 0.39, 95% confidence interval 0.2 to 0.8). Left ventricular size
decreased (systolic diameter 3.9+/-0.3 vs 4.6+/-0.2 cm, p=0.0008 and diastolic
diameter 5.2+/-0.2 vs 5.7+/-0.2 cm, p=0.002) and ejection fraction increased
(39.1+/-4.0% vs 33.1+/-1.9%, p=0.002) significantly after PCI in the patients
with improvement in IMR compared with patients without improvement. Patients with
improvement in IMR had numerically better survival; however, it was not
statistically significant (p log-rank=0.2). In conclusion, 1/3 of the patients
with IMR had improvement in severity of IMR with PCI alone. Improvement in IMR
was associated with left ventricular reverse remodeling. Left atrial size was an
important predictor of improvement in IMR after PCI.
PMID- 25118124
TI - Rate of percutaneous coronary intervention for the management of acute coronary
syndromes and stable coronary artery disease in the United States (2007 to 2011).
AB - Although the benefit of percutaneous coronary interventions (PCIs) for patients
presenting with acute coronary syndromes (ACS) has been established in numerous
studies, the role of PCI in stable coronary artery disease (CAD) remains
controversial. With the publication of the Clinical Outcomes Utilizing
Revascularization and Aggressive Drug Evaluations trial and the appropriate use
criteria for coronary artery revascularization, we sought to examine the impact
of these treatment strategies and guidelines on the current practice of PCI in
United States. We conducted a serial cross-sectional study with time trends of
patients undergoing PCI for ACS and stable CAD from 2007 to 2011. The annual rate
of all PCI decreased by 27.7% from 10,785 procedures per million adults per year
in 2007 to 2008 to 7,801 procedures per million adults per year in 2010 to 2011
(p=0.03). Although there was no statistically significant decrease in the PCI
utilization for ACS from 2007 to 2011, PCI utilization for stable CAD decreased
by 51.7% (from 2,056 procedures per million adults per year in 2008 to 992
procedures per million adults per year in 2011, p=0.02). Hospitals with a higher
volume of PCI experienced a more significant decrease. Decrease in PCI
utilization for stable CAD was statistically significant for patients with
Medicare and private insurance/health maintenance organization (44.5%, p=0.03 and
59.5%, p=0.007, respectively). In conclusion, the rate of PCI decreased
substantially starting from 2009 in the United States. Most of the decrease was
attributed to the reduction in PCI utilization for stable CAD.
PMID- 25118125
TI - Bipolar disorder and its relation to major psychiatric disorders: a family-based
study in the Swedish population.
AB - OBJECTIVES: Bipolar disorder (BPD) shares genetic components with other
psychiatric disorders; however, uncertainty remains about where in the
psychiatric spectra BPD falls. To understand the etiology of BPD, we studied the
familial aggregation of BPD and co-aggregation between BPD and schizophrenia,
depression, anxiety disorders, attention-deficit hyperactivity disorder, drug
abuse, personality disorders, and autism spectrum disorders. METHODS: A
population-based cohort was created by linking several Swedish national
registers. A total of 54,723 individuals with BPD were identified among 8,141,033
offspring from 4,149,748 nuclear families. The relative risk of BPD in relatives
and the co-occurrence of other psychiatric disorders in patients with BPD and
their relatives were compared to those of matched-population controls. Structural
equation modeling was used to estimate the heritability and tetrachoric
correlation. RESULTS: The familial risks for relatives of BPD probands were 5.8
7.9 in first-degree relatives, and decreased with genetic distance. Co-occurrence
risks for other psychiatric disorders were 9.7-22.9 in individuals with BPD and
1.7-2.8 in full siblings of BPD probands. Heritability for BPD was estimated at
58%. The correlations between BPD and other psychiatric disorders were
considerable (0.37-0.62) and primarily due to genetic effects. The correlation
with depression was the highest (0.62), and was 0.44 for schizophrenia.
CONCLUSIONS: The high familial risks provide evidence that genetic factors play
an important role in the etiology of BPD, and the shared genetic determinants
suggest pleiotropic effects across different psychiatric disorders. Results also
indicate that BPD is in both the mood and psychotic spectra, but possibly more
closely related to mood disorders.
PMID- 25118126
TI - The effect of different delineator post configurations on driver speed in night
time traffic: a driving simulator study.
AB - The aim of the study was to investigate how different delineator post
configurations affect driver speed in night-time traffic. In addition, the
potential speed effect of introducing a secondary task was investigated. The
study was carried out in a car simulator on a road stretch including straight
road sections as well as curves with different radii. Fourteen drivers
participated in the study and the results show that absence of delineator posts
leads to reduced speed. However, provided that there are delineator posts
continuously present along the road, the overall driver speed is basically the
same, regardless of the spacing between the delineator posts. The results also
imply that to reduce driver speed in curves with small radius, using more compact
spacing of posts in these curves as compared to in curves with a larger radius,
could be a potential strategy. Additionally, the speed reducing effect of a
secondary task was only prevailing where the task was initiated.
PMID- 25118127
TI - Why do organizations not learn from incidents? Bottlenecks, causes and conditions
for a failure to effectively learn.
AB - If organizations would be able to learn more effectively from incidents that
occurred in the past, future incidents and consequential injury or damage can be
prevented. To improve learning from incidents, this study aimed to identify
limiting factors, i.e. the causes of the failure to effectively learn. In seven
organizations focus groups were held to discuss factors that according to
employees contributed to the failure to learn. By use of a model of the learning
from incidents process, the steps, where difficulties for learning arose, became
visible, and the causes for these difficulties could be studied. Difficulties
were identified in multiple steps of the learning process, but most difficulties
became visible when planning actions, which is the phase that bridges the gap
from incident investigation to actions for improvement. The main causes for
learning difficulties, which were identified by the participants in this study,
were tightly related to the learning process, but some indirect causes - or
conditions - such as lack of ownership and limitations in expertise were also
mentioned. The results illustrate that there are two types of causes for the
failure to effectively learn: direct causes and indirect causes, here called
conditions. By actively and systematically studying learning, more conditions
might be identified and indicators for a successful learning process may be
determined. Studying the learning process does, however, require a shift from
learning from incidents to learning to learn.
PMID- 25118128
TI - Causes of fatal accidents for instrument-certified and non-certified private
pilots.
AB - Instrument certification (IFR) enhances a pilot's skills in precisely controlling
the aircraft and requires a higher level of standards in maintaining heading and
altitude compared with the less stringent private pilot certificate. However,
there have been no prior studies to compare fatal accident causes for airmen
with, and without, this rating, The NTSB accident database was queried for
general aviation fatal accidents for private pilots with, and without IFR
certification. Exact Poisson tests were used to calculate whether two rate
parameters were equal (ratio of 1), normalized to the number of IFR-rated pilots
and flight hours in the given time period. Proportion tests were used to
determine whether there were significant differences in fatal accident causes
between IFR-certified and non-certified pilots. A logistic regression for log
odds success was used in determining the trend and effect of age on fatal
accident rates. IFR certification was associated with a reduced risk of accidents
due to failure to maintain obstacle/terrain clearance and spatial disorientation
for day and night operations respectively. In contrast, the likelihood of fatal
accident due to equipment malfunction during day operations was higher for IFR
certified pilots. The fatal accident rate decreased over the last decade for IFR
certified but not for non-IFR-certified private pilots. However, the overall
accident rate for IFR-certified private pilots was more than double that of the
cohort lacking this certification. Finally, we found a trend for an increased
fatality rate with advancing age for both group of pilots. Our findings informs
on where training and/or technology should be focused. Both training for
aerodynamic stalls, which causes over a quarter of all fatal accidents, should be
intensified for both IFR-certified and non-certified private pilots. Similarly,
adherence to minimum safe altitudes for both groups of pilots should be
encouraged toward reducing the fatal accidents rate due to failure to maintain
obstacle/terrain clearance. For night operations, the high percentage of
accidents due to spatial disorientation for non-IFR certified airmen suggests
that additional training be required for such operations or such flights carry
restrictions for this subset of pilots.
PMID- 25118129
TI - Multifamily psychoeducation for improvement of mental health among relatives of
patients with major depressive disorder lasting more than one year: study
protocol for a randomized controlled trial.
AB - BACKGROUND: Major depressive disorder (MDD) is a long-lasting disorder with
frequent relapses that have significant effects on the patient's family. Family
psychoeducation is recognized as part of the optimal treatment for patients with
psychotic disorder. A previous randomized controlled trial has found that family
psychoeducation is effective in enhancing the treatment of MDD. Although MDD can
easily become a chronic illness, there has been no intervention study on the
families of patients with chronic depression. In the present study, we design a
randomized controlled trial to examine the effectiveness of family
psychoeducation in improving the mental health of relatives of patients with MDD
lasting more than one year. METHODS/DESIGN: Participants are patients with MDD
lasting more than one year and their relatives. Individually randomized, parallel
group trial design will be employed. Participants will be allocated to one of two
treatment conditions: relatives will receive (a) family psychoeducation (four,
two-hour biweekly multifamily psychoeducation sessions) plus treatment-as-usual
for the patient (consultation by physicians), or (b) counseling for the family
(one counseling session from a nurse) plus treatment-as-usual for the patient.
The primary outcome measure will be relatives' mental health as measured by K6
that was developed to screen for DSM-IV depressive and anxiety disorder.
Additionally, the severity of depressive symptoms in patients measured by the
Beck Depression Inventory-II (BDI-II) scale will be assessed. Data from the
intention-to-treat sample will be analyzed 16 weeks after randomization.
DISCUSSION: This is the first study to evaluate the effectiveness of family
psychoeducation for relatives of patients with MDD lasting more than one year. If
this type of intervention is effective, it could be a new method of
rehabilitation for patients with MDD lasting more than one year. TRIAL
REGISTRATION: Clinical Trials.gov NCT01734291 (registration date: 18 October
2012).
PMID- 25118135
TI - Whole-of-society approach for public health policymaking: a case study of
polycentric governance from Quebec, Canada.
AB - In adopting a whole-of-society (WoS) approach that engages multiple stakeholders
in public health policies across contexts, the authors propose that effective
governance presents a challenge. The purpose of this paper is to highlight a case
for how polycentric governance underlying the WoS approach is already
functioning, while outlining an agenda to enable adaptive learning for improving
such governance processes. Drawing upon a case study from Quebec, Canada, we
employ empirically developed concepts from extensive, decades-long work of the
2009 Nobel laureate Elinor Ostrom in the governance of policy in nonhealth
domains to analyze early efforts at polycentric governance in policies around
overnutrition, highlighting interactions between international, domestic, state
and nonstate actors and processes. Using information from primary and secondary
sources, we analyze the emergence of the broader policy context of Quebec's
public health system in the 20th century. We present a microsituational analysis
of the WoS approach for Quebec's 21st century policies on healthy lifestyles,
emphasizing the role of governance at the community level. We argue for
rethinking prescriptive policy analysis of the 20th century, proposing an agenda
for diagnostic policy analysis, which explicates the multiple sets of actors and
interacting variables shaping polycentric governance for operationalizing the WoS
approach to policymaking in specific contexts.
PMID- 25118134
TI - Distribution of perfluoroalkyl compounds in rats: Indication for using hair as
bioindicator of exposure.
AB - Hair analysis is potentially advantageous in exposure assessment of
perfluoroalkyl acids (PFAAs) as a non-invasive method, combined with the ability
to reflect long-term exposure. The present study aims to assess the feasibility
of using hair as an indicator of PFAA exposure. Adult male and female rats were
subchronically exposed to selected PFAAs, including perfluorooctanoic acid
(PFOA), perfluorononanoic acid (PFNA), and perfluorooctanesulfonate (PFOS), for
90 days. Hair, serum, and other tissues, including liver, kidney, spleen, lung,
brain and heart, as well as the urine and feces excretions, were analyzed for
PFAA levels. PFOA/PFNA/PFOS were detected in rat hair in a dose-dependent manner,
in the order of PFOS>PFNA>PFOA. Hair PFAA concentrations were higher in male rats
than the female rats, except for PFOS at low dose. Moreover, significant positive
correlations as well as similar PFAA profiles were observed between hair, serum,
and other tissues. Besides, hair PFAAs were negatively correlated with the
urinary excretion rate. Although the influencing factors in humans still need
further investigation, the results suggested that hair is capable of reflecting
PFAA exposure, and could be employed as an alternative exposure bioindicator of
PFAAs.
PMID- 25118136
TI - Towards large scale fermentative production of succinic acid.
AB - Fermentative production of succinic acid (SA) from renewable carbohydrate feed
stocks can have the economic and sustainability potential to replace petroleum
based production in the future, not only for existing markets, but also new
larger volume markets. To accomplish this, extensive efforts have been undertaken
in the field of strain construction and metabolic engineering to optimize SA
production in the last decade. However, relatively little effort has been put
into fermentation process development. The choice for a specific host organism
determines to a large extent the process configuration, which in turn influences
the environmental impact of the overall process. In the last five years,
considerable progress has been achieved towards commercialization of fermentative
production of SA. Several companies have demonstrated their confidence about the
economic feasibility of fermentative SA production by transferring their
processes from pilot to production scale.
PMID- 25118137
TI - Mammalian cell-produced therapeutic proteins: heterogeneity derived from protein
degradation.
AB - Therapeutic glycoproteins, for example, antibodies (Abs) and Fc fusion proteins
when produced in mammalian cells, such as Chinese hamster ovary (CHO) cells
generally exhibit heterogeneity. Both the oligosaccharide moiety and the protein
moiety contribute to this phenomenon. Non-enzymatic and enzymatic pathways of
protein fragmentation generate heterogeneity in the polypeptide backbone. In the
non-enzymatic pathway, physical and chemical events such as light, oxidation, and
others can cause the protein moiety to become unstable leading to its
fragmentation. Intracellular and secreted proteases are involved in the enzymatic
degradation of proteins. This degradative process is modulated by the
oligosaccharide moiety of the glycoprotein as well as glycosidases, including
sialidases that are secreted in the culture medium. This review focuses on the
factors that modulate heterogeneity of the protein moiety especially by the
enzymatic methods. Availability of the CHO genome database will facilitate the
development of host cell lines with minimal degradative properties.
PMID- 25118138
TI - Placental lipases in pregnancies complicated by gestational diabetes mellitus
(GDM).
AB - Infants of women with gestational diabetes mellitus (GDM) are more likely to be
born large for gestational age with a higher percentage body fat. Elevated
maternal lipids may contribute to this. Placental lipases such as lipoprotein
lipase (LPL), endothelial lipase (EL) and hormone sensitive lipase (HSL) are
involved in transferring lipids from mother to fetus. Previous studies of
expression of these lipases in placentae in women with diabetes in pregnancy have
reported divergent results. Intracellular lipases such as adipose triglyceride
lipase (ATGL), and HSL are central to lipid droplet metabolism. The activities of
these lipases are both influenced by Perilipin 1, and ATGL is also activated by a
co-factor comparative gene identification-58 (CGI-58) and inhibited by G0/G1
switch gene 2 (GS02). None of these modifying factors or ATGL have been examined
previously in placenta. The purpose of this study was therefore to examine the
expression of ATGL, HSL, LPL, EL, as well as Perilipin 1, GS02 and CGI-58 in term
pregnancies complicated by GDM. mRNA and protein expression of the lipases were
measured in placentae from 17 women with GDM and 17 normoglycaemic pregnancies,
matched for maternal BMI and gestational age of delivery. ATGL mRNA expression
was increased and HSL mRNA expression reduced in placentae from GDM although
there was no differences in protein expression of any of the lipases. All lipases
were localised to trophoblasts and endothelial cells. The expression of Perilipin
1 and CGI-58 mRNA was increased and GS02 not altered in GDM. These results
suggest that there is no difference in expression in these four lipases between
GDM and normoglycaemic placentae, and therefore altered lipid transfer via these
lipases does not contribute to large for gestational age in infants of women with
GDM.
PMID- 25118139
TI - Use of psychotherapy in a representative adult community sample in Sao Paulo,
Brazil.
AB - Little is known about the use of psychotherapy to treat common mental disorders
in a major city in a middle-income country. Our data come from in-home interviews
with a stratified random sample of 2000 community residents aged 18 to 65 years
in the city of Sao Paulo, Brazil. The information obtained included
sociodemographic characteristics; psychotropic drugs; mental status; and
lifetime, previous 12 months, and current use of psychotherapy. Logistic
regression was used to examine determinants of use of psychotherapy. Of the
sample, 22.7% met General Health Questionnaire-12 criteria for common mental
disorders. Lifetime, previous 12 months, and current use of psychotherapy were
reported by 14.6%, 4.6%, and 2.3% of the sample, respectively. Users typically
were women, were more educated, had higher income, were not married, were
unemployed, and had common mental disorders. Further analysis found that 47%
(with higher education and income) paid out-of-pocket, and 53% used psychotropic
medication. Psychotherapy does not seem to be the preferred treatment of common
mental disorders.
PMID- 25118140
TI - Elevated levels of urinary markers of oxidatively generated DNA and RNA damage in
bipolar disorder.
AB - OBJECTIVES: The pathophysiological mechanisms underlying bipolar disorder and its
multi-system nature are unclear. Oxidatively generated damage to nucleosides has
been demonstrated in metabolic disorders; however, the extent to which this
occurs in bipolar disorder in vivo is unknown. We investigated oxidatively
generated damage to DNA and RNA in patients with bipolar disorder and its
relationship with the affective phase compared with healthy control subjects.
METHODS: Urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8
oxo-7,8-dihydroguanosine (8-oxoGuo), markers of oxidatively generated DNA and RNA
damage, respectively, was measured in 37 rapid cycling patients with bipolar
disorder and in 40 age- and gender-matched healthy control subjects. Employing a
longitudinal design, repeated measurements of both markers were evaluated in
various affective phases in patients with bipolar disorder during a six- to 12
month period and compared with repeated measurements in healthy control subjects.
RESULTS: In linear mixed models, adjusting for demographical, metabolic, and
lifestyle factors, the excretion of 8-oxodG and 8-oxoGuo was significantly
elevated in euthymic patients with bipolar disorder compared with healthy control
subjects, with increases of 40% (p < 0.0005) and 43% (p < 0.0005), respectively.
The increased oxidatively generated nucleoside damage was present through all
affective phases of the illness, with no significant difference between affective
states. CONCLUSIONS: Our results indicate that bipolar disorder is associated
with increased oxidatively generated damage to nucleosides. The findings could
suggest a role for oxidatively generated damage to DNA and RNA as a molecular
mechanism contributing to the increased risk of medical disorders, shortened life
expectancy, and the progressive course of illness observed in bipolar disorder.
PMID- 25118147
TI - Mediterranean Diet and Cardiovascular Risk: Beyond Traditional Risk Factors.
AB - A strict adherence to the Mediterranean Diet (MedDiet) has repeatedly been linked
to a low risk of cardiovascular disease in several situations. Initially, the
mechanisms considered as possible causes of this were based on the effects of
this dietary pattern on the so-called traditional risk factors (especially lipids
and blood pressure). However, the high relative reduction in the prevalence of
cardiovascular morbidity and mortality were not proportional to the limited
findings about regulation of those traditional risk factors. In addition to
several studies confirming the above effects, current research on the MedDiet is
being focused on defining its effects on non-traditional risk factors, such as
endothelial function, inflammation, oxidative stress, or on controlling the
conditions which predispose people to cardiovascular events, such as obesity,
metabolic syndrome or type 2 diabetes mellitus. In the current article, after
briefly reviewing the known effects of the MedDiet on the traditional risk
factors, we will mainly focus on reviewing the current evidence about the effects
that this dietary pattern exerts on alternative factors, including postprandial
lipemia or coagulation, among others, as well as providing a short review on
future directions.
PMID- 25118148
TI - The importance of dietary protein for muscle health in inactive, hospitalized
older adults.
AB - Dietary protein and amino acids are necessary for overall human health.
Insufficient protein intake induces a negative protein balance with adverse
outcomes such as muscle atrophy and functional decline--outcomes that are
worsened in older adults. Furthermore, during inactivity, such as bed
rest/hospitalization, skeletal muscle protein synthesis is reduced, protein
balance is negative, and older adults lose significant amounts of muscle. Dietary
protein and amino acid supplementation (~ 30 g protein and ~ 3 g leucine)
stimulate skeletal muscle protein anabolism in healthy, community-dwelling older
adults and may be considered as possible nutritional interventions to improve the
muscle protein balance and potentially support skeletal muscle maintenance in
hospitalized older adults. The following is a timely review of metabolic and
dietary challenges faced by hospitalized older adults and potential dietary
protein and amino acids solutions for maintaining skeletal muscle health during
hospitalization-induced inactivity in this population.
PMID- 25118146
TI - Effect of guided self-determination youth intervention integrated into outpatient
visits versus treatment as usual on glycemic control and life skills: a
randomized clinical trial in adolescents with type 1 diabetes.
AB - BACKGROUND: Providing care for adolescents with type 1 diabetes is complex,
demanding, and often unsuccessful. Guided self-determination (GSD) is a life
skills approach that has been proven effective in caring for adults with type 1
diabetes. To improve care, GSD was revised for adolescents, their parents, and
interdisciplinary healthcare providers (HCP) to create GSD-Youth (GSD-Y). We
evaluated the impact of GSD-Y after it was integrated into pediatric outpatient
visits versus treatment-as-usual, focusing on glycemic control and the
development of life skills in adolescents with type 1 diabetes. METHODS: Seventy
one adolescents (mean age: 15 years, mean duration of diabetes: 5.7 years, mean
HbA1c: 77 mmol/mol (9.1%), upon entering the study) from two pediatric
departments were randomized into a GSD-Y group (n = 37, GSD-Y was provided during
individual outpatient sessions) versus a treatment-as-usual group (n = 34). The
primary outcome was the HbA1c measurement. The secondary outcomes were life
skills development (assessed by self-reported psychometric scales), self
monitored blood glucose levels, and hypo- and hyperglycemic episodes. The
analysis followed an intention-to-treat basis. RESULTS: Fifty-seven adolescents
(80%) completed the trial, and 53 (75%) completed a six-month post-treatment
follow-up. No significant effect of GSD-Y on the HbA1c could be detected in a
mixed-model analysis after adjusting for the baseline HbA1c levels and the
identity of the HCP (P = 0.85). GSD-Y significantly reduced the amotivation for
diabetes self-management after adjusting for the baseline value (P = 0.001).
Compared with the control group, the trial completion was prolonged in the GSD-Y
group (P <0.001), requiring more visits (P = 0.05) with a higher rate of non
attendance (P = 0.01). GSD-Y parents participated in fewer of the adolescents'
visits (P = 0.05) compared with control parents. CONCLUSIONS: Compared with
treatment-as-usual, GSD-Y did not improve HbA1c levels, but it did decrease
adolescents' amotivation for diabetes self-management. TRIAL REGISTRATION: ISRCTN
54243636, registered on 10 January 2010. Life skills for adolescents with type 1
diabetes and their parents.
PMID- 25118149
TI - Effect of operating conditions on yield and quality of biocrude during
hydrothermal liquefaction of halophytic microalga Tetraselmis sp.
AB - The biomass of halophytic microalga Tetraselmis sp. with 16%w/w solids was
converted into biocrude by a hydrothermal liquefaction (HTL) process in a batch
reactor at different temperatures (310, 330, 350 and 370 degrees C) and reaction
times (5, 15, 30, 45 and 60min). The biocrude yield, elemental composition,
energy density and severity parameter obtained at various reaction conditions
were used to predict the optimum condition for maximum recovery of biocrude with
improved quality. This study clearly indicated that the operating condition for
obtaining maximum biocrude yield and ideal quality biocrude for refining were
different. A maximum biocrude yield of ~65wt% ash free dry weight (AFDW) was
obtained at 350 degrees C and 5min, with a severity parameter and energy density
of 5.21 and ~35MJ/kg, respectively. The treatment with 45min reaction time
recorded ~62wt% (AFDW) yield of biocrude with and energy density of ~39MJ/kg and
higher severity parameter of 7.53.
PMID- 25118150
TI - Phosphorus elimination from aqueous solution using 'zirconium loaded okara' as a
biosorbent.
AB - This work deals with the capture of phosphorus from aqueous solutions by
biosorption onto zirconium loaded okara (ZLO). The batch-mode experiments were
conducted to examine the effect of pH, biosorbent dose, initial phosphorus
concentration, contact time, and temperature on the process. It was found that,
the adsorption was most favored in the pH range of 2-6. The optimal doses for the
adsorption, at initial phosphorus concentrations of 5, 10, 25, 50mg/L were 2, 3,
7, 10g/L, respectively. The maximum adsorption capacity of ZLO was approximately
44.13mg PO4/g at 298K. The phosphate removal was rapid, reaching 95% in 30min.
Freundlich model best fitted the equilibrium data, while Pseudo-second order
model satisfactorily described the kinetic results. Thermodynamic analysis
revealed feasible, spontaneous, and endothermic nature of the process. The
research would be beneficial for developing a promising, eco-friendly phosphorus
biosorbent from a plentiful AWB - okara.
PMID- 25118151
TI - Enhanced pathway efficiency of Saccharomyces cerevisiae by introducing thermo
tolerant devices.
AB - In this study, thermo-tolerant devices consisting of heat shock genes from
thermophiles were designed and introduced into Saccharomyces cerevisiae for
improving its thermo-tolerance. Among ten engineered thermo-tolerant yeasts, T.te
TTE2469, T.te-GroS2 and T.te-IbpA displayed over 25% increased cell density and
1.5-4-fold cell viability compared with the control. Physiological
characteristics of thermo-tolerant strains revealed that better cell wall
integrity, higher trehalose content and enhanced metabolic energy were preserved
by thermo-tolerant devices. Engineered thermo-tolerant strain was used to
investigate the impact of thermo-tolerant device on pathway efficiency by
introducing beta-amyrin synthesis pathway, showed 28.1% increased beta-amyrin
titer, 28-35 degrees C broadened growth temperature range and 72h shortened
fermentation period. The results indicated that implanting heat shock proteins
from thermophiles to S. cerevisiae would be an efficient approach to improve its
thermo-tolerance.
PMID- 25118154
TI - Are trials with nursing interventions pragmatic?
PMID- 25118152
TI - Effects of earthworms on physicochemical properties and microbial profiles during
vermicomposting of fresh fruit and vegetable wastes.
AB - This study aimed to investigate the effect of earthworms on physicochemical and
microbial properties during vermicomposting of fresh fruit and vegetable wastes
(FVW) by contrasting two decomposing systems of FVW with and without earthworms
for 5weeks. Compared to control treatment (without earthworms), vermicomposting
treatment resulted in a rapid decrease of electrical conductivity and losses of
total carbon and nitrogen from the 2nd week. Quantitative PCR displayed that
earthworms markedly enhanced bacterial and fungal densities, showing the higher
values than control, during the whole decomposition process. In addition,
denaturing gradient gel electrophoresis combined with sequencing analysis
revealed that earthworms pronouncedly modified bacterial and fungal community
structures, through broadening the community diversities of Actinobacteria,
Bacteroidetes, Proteobacteria, and Ascomycotina. These results suggest that the
presence of earthworms promoted the activity and population of bacteria and
fungi, and modified their communities, thus altering the decomposition pathway of
fresh FVW.
PMID- 25118155
TI - Nonlinear dynamics of mood regulation in bipolar disorder.
AB - OBJECTIVES: We sought to study the underlying dynamic processes involved in mood
regulation in subjects with bipolar disorder and healthy control subjects using
time-series analysis and to then analyze the relation between anxiety and mood
using cross-correlation techniques. METHODS: We recruited 30 healthy controls and
30 euthymic patients with bipolar disorder. Participants rated their mood,
anxiety, and energy levels using a paper-based visual analog scale; and they also
recorded their sleep and any life events. Information on these variables was
provided over a three-month period on a daily basis, twice per day. We analyzed
the data using Box-Jenkins time series analysis to obtain information on the
autocorrelation of the series (for mood) and cross-correlation (mood and anxiety
series). RESULTS: Throughout the study, we analyzed 10,170 data points. Self
ratings for mood, anxiety, and energy were normally distributed in both groups.
Autocorrelation functions for mood in both groups were governed by the
autoregressive integrated moving average (ARIMA) (1,1,0) model, which means that
current values in the series were related to one previous point only. We also
found a negative cross-correlation between mood and anxiety. CONCLUSIONS: Mood
can be considered a memory stochastic process; it is a flexible, dynamic process
that has a 'short memory' both in healthy controls and euthymic patients with
bipolar disorder. This process may be quite different in untreated patients or in
those acutely ill. Our results suggest that nonlinear measures can be applied to
the study of mood disorders.
PMID- 25118156
TI - Feasibility of a randomized controlled trial of functional strength training for
people between six months and five years after stroke: FeSTivaLS trial.
AB - BACKGROUND: Functional Strength Training (FST) could enhance recovery late after
stroke. The aim of this study was to evaluate the feasibility of a subsequent
fully powered, randomized controlled trial. METHODS: The study was designed as a
randomized, observer-blind trial. Both interventions were provided for up to one
hour a day, four days a week, for six weeks. Evaluation points were before
randomization (baseline), after six weeks intervention (outcome), and six weeks
thereafter (follow-up). The study took place in participants' own homes.
Participants (n = 52) were a mean of 24.4 months after stroke with a mean age of
68.3 years with 67.3% male. All had difficulty using their paretic upper (UL) and
lower limb (LL). Participants were allocated to FST-UL or FST-LL by an
independent randomization service. The outcome measures were recruitment rate,
attrition rate, practicality of recruitment strategies, occurrence of adverse
reactions, acceptability of FST, and estimation of sample size for a subsequent
trial. Primary clinical efficacy outcomes were the Action Research Arm Test
(ARAT) and the Functional Ambulation Categories (FAC). Analysis was conducted
using descriptive statistics and thematic analysis of participants' views of FST.
A power calculation used estimates of clinical efficacy variance to estimate
sample size for a subsequent trial. RESULTS: The screening process identified
1,127 stroke survivors of whom 52 (4.6%) were recruited. The recruitment rate was
higher for referral from community therapists than for systematic identification
of people discharged from an acute stroke unit. The attrition rate was 15.5% at
the outcome and follow-up time-points. None of the participants experienced an
adverse reaction. The participants who remained in the study at outcome had
received 68% of the total possible amount of therapy. Participants reported that
their experience of FST provided a sense of purpose and involvement and increased
their confidence in performing activities. The power calculation provides
estimation that 150 participants in each group will be required for a subsequent
clinical trial. CONCLUSIONS: This study found that a subsequent clinical trial
was feasible with modifications to the recruitment strategy to be used. TRIAL
REGISTRATION: Controlled-trials.com ISCTN71632550, 30 January 2009.
PMID- 25118159
TI - Co-inheritance of alpha-thalassaemia and beta-thalassaemia in a prenatal
screening population in mainland China.
AB - OBJECTIVE: To determine the prevalence of alpha-thalassaemia in beta-thalassaemia
individuals in a Chinese population. METHODS: The standard diagnostic marker for
beta-thalassaemia was elevation of the Hb A2 level (>3.5%) with low mean
corpuscular volume. The common alpha-thalassaemia mutations were studied by
molecular analysis in all identified beta-thalassaemia carriers. RESULTS: A
prevalence rate of 3.3% for beta-thalassaemia was found in our population; alpha-
and beta-thalassaemia interactions were found to co-exist in 17.8% of the beta
thalassaemia carriers. The -SEA deletion was the most common alpha-thalassaemia
mutation co-inherited with beta-thalassaemia, followed by the -alpha3.7 deletion,
the -alpha4.2 deletion, Hb Quong Sze, and Hb Constant Spring. CONCLUSION: Our
results suggest that it could be valuable to study co-existing alpha-globin
mutations in subjects with beta-thalassaemia trait in a prenatal screening
programme, especially in populations with a high prevalence of
haemoglobinopathies.
PMID- 25118157
TI - Toll-like receptor 3 activation is required for normal skin barrier repair
following UV damage.
AB - UV damage to the skin leads to the release of noncoding RNA (ncRNA) from necrotic
keratinocytes that activates Toll-like receptor 3 (TLR3). This release of ncRNA
triggers inflammation in the skin following UV damage. Recently, TLR3 activation
was also shown to aid wound repair and increase the expression of genes
associated with permeability barrier repair. Here, we sought to test whether skin
barrier repair after UVB damage is dependent on the activation of TLR3. We
observed that multiple ncRNAs induced expression of skin barrier repair genes,
that the TLR3 ligand Poly (I:C) also induced expression and function of tight
junctions, and that the ncRNA U1 acts in a TLR3-dependent manner to induce
expression of skin barrier repair genes. These observations were shown to have
functional relevance as Tlr3-/- mice displayed a delay in skin barrier repair
following UVB damage. Combined, these data further validate the conclusion that
recognition of endogenous RNA by TLR3 is an important step in the program of skin
barrier repair.
PMID- 25118158
TI - Identifying a polymorphic 'switch' that influences miRNAs' regulation of a
myasthenia gravis risk pathway.
AB - The significant roles of genetic variants in myasthenia gravis (MG) pathogenesis
have been demonstrated in many studies, and recently it has been revealed that
aberrant level/regulation of microRNAs (miRNAs) might contribute to the
initiation and progression of MG. However, the dysfunction of miRNA associated
with single nucleotide polymorphisms (miRSNPs) has not been well investigated in
MG. In this study, we created a contemporary catalog of 89 MG risk genes via
manual literature-mining. Based on this risk gene catalog, we obtained 18 MG risk
pathways. Furthermore, we identified 93 miRNAs that target MG risk pathways and
revealed the miRSNPs 'switches' in miRNA regulation in the MG risk pathways by
integrating the database information of miRSNPs. We also constructed a miRNA
mediated SNP switching pathway network (MSSPN) to intuitively analyze miRNA
regulation of MG risk pathways and the relationship of the polymorphism 'switch'
with these changes in regulation. Moreover, we carried out in-depth dissection on
the correlation between hsa05200 (pathway in cancer) and MG development, and
elaborated the significance of 4 high-risk genes. By network analysis and
literature mining, we proposed a potential mechanism of miRSNPs->gene->pathway
effects on MG pathogenesis, especially for rs28457673 (miR-15/16/195/424/497
family)->IGF1R->hsa05200 (pathway in cancer). Therefore, our studies have
revealed a functional role for genetic modulators in MG pathogenesis at a
systemic level, which could be informative for further miRNA and miRSNPs studies
in MG.
PMID- 25118161
TI - Academic vascular unit collaboration with advertising agency yields higher
compliance in screening for abdominal aortic aneurysm.
AB - To improve compliance with abdominal aortic aneurysm (AAA) screening in low
compliance areas, individually tailored invitations were developed in
collaboration with a professional advertising agency. Compliance increased in two
intervention municipalities from 71.4% in 2010-2012 to 78.1% in 2013 (p = 0.025),
and was then higher [odds ratio 1.7; 95% confidence interval 1.1-2.6; p = 0.013]
than in two control municipalities in which compliance was unchanged (417/552
[75.5%] in 2010-12 and 122/180 [67.8%] in 2013). Compliance with AAA-screening
can be increased by collaboration with a professional advertising agency, albeit
at a comparably high cost.
PMID- 25118162
TI - Axillary burden of disease following false-negative preoperative axillary
evaluation.
AB - BACKGROUND: Preoperative axillary ultrasound (AUS) and fine-needle aspiration
(FNA) are sensitive and specific for breast cancer nodal metastases. We
hypothesize that false-negative result predicts minimal axillary disease (<=2
+nodes). METHODS: A retrospective review of breast cancer patients receiving AUS
identified T1/T2 tumors and positive sentinel node with axillary dissection. Chi
square analysis was performed using Fisher's exact test. RESULTS: Of 903 AUS
cases, 384 had T1/T2 tumors. False-negative rate of AUS +/- FNA was 48% and 45%,
respectively. Of 384 cases, 73 were sentinel node positive and had axillary
dissection; 55 (75.3%) were invasive ductal carcinoma (IDC). Negative predictive
value for greater than or equal to 2 nodes was 71% in IDC versus 44% for in non
IDC patients. Sixteen (29.0%) IDC patients had greater than or equal to 3
positive nodes versus 10 (55.5%) non-IDC (P = .05) patients. CONCLUSION: The high
negative predictive value for AUS with FNA for IDC suggests that the AUS plus FNA
interpretation may be better limited to the ipsilateral nodes of IDC.
PMID- 25118160
TI - Geographic variation in radiologist capacity and widespread implementation of
lung cancer CT screening.
AB - BACKGROUND: Newly released United States Preventive Services Task Force (USPSTF)
recommendations for lung cancer screening are expected to increase demand for low
dose computed tomography scanning, but health system capacity constraints might
threaten the scale-up of screening. OBJECTIVES: To estimate the prevalence of
capacity constraints in the radiologist workforce and resulting potential
disparities in access to lung cancer screening. METHODS: We combined information
from health interview surveys to estimate the numbers of smokers who meet the
USPSTF eligibility criteria, and information from administrative datasets to
estimate the numbers of radiologists and the numbers of scans they currently
interpret in Health Service Areas (HSAs) nationwide. We estimated and mapped the
prevalence of capacity constrained HSAs - those having a greater than 5% or
greater than 25% projected increase in scans over current levels from scaling up
screening - and used descriptive statistics and logistic regressions to identify
HSA characteristics associated with capacity constraints. RESULTS: Scaling up
lung cancer screening would increase imaging procedures by an average of 4%
across HSAs. Of the 9.6 million eligible smokers, 1,023,943 lived in HSAs with
increases of at least 5%. HSAs that were rural, with many eligible smokers, and
disproportionately Hispanic or low-income smokers had significantly higher odds
of facing capacity constraints. CONCLUSIONS: Disparities in access to lung cancer
screening appear likely unless policy makers target HSAs with few radiologists
for additional resources. Radiologists should be able to absorb the workload
imposed by lung cancer screening in most areas of the country.
PMID- 25118163
TI - Repair of recurrent hernia after biologic mesh failure in abdominal wall
reconstruction.
AB - BACKGROUND: Biologic mesh is commonly used in abdominal wall reconstruction but
may result in increased hernia recurrence. There are minimal data on repair of
these recurrent hernias. METHODS: We conducted a retrospective chart review of 24
patients presenting to a single surgeon with recurrent ventral hernia, previously
repaired with biologic mesh. RESULTS: Seventeen of 24 study patients underwent
open repair, including 5 revisions of incomplete external oblique release. Mesh
was polypropylene in 11 patients and fenestrated condensed
polytetrafluoroethylene in 3 patients. In 1 patient, no mesh was used. In 2
patients, bridged biologic mesh was used because of risk of exposure. All
biologic repairs have since recurred. Complications occurred in 3 of 15
prosthetic mesh patients and in all biologic mesh patients. CONCLUSIONS: Prior
components release can be repeated if computed tomography scan reveals incomplete
release. Recurrence is common after bridged biologic mesh repair. Conventional
mesh can be used safely in many recurrent abdominal hernias after biologic mesh
failure.
PMID- 25118165
TI - A small intestinal organoid model of non-invasive enteric pathogen-epithelial
cell interactions.
AB - Organoids mirror in vivo tissue organization and are powerful tools to
investigate the development and cell biology of the small intestine. However,
their application for the study of host-pathogen interactions has been largely
unexplored. We have established a model using microinjection of organoids to
mimic enteric infection, allowing for direct examination of pathogen interactions
with primary epithelial cells in the absence of confounding variables introduced
by immune cells or the commensal microbiota. We investigated the impact of Paneth
cell alpha-defensin antimicrobial peptides on bacterial growth. We demonstrate
that organoids form a sealed lumen, which contains concentrations of alpha
defensins capable of restricting growth of multiple strains of Salmonella
enterica serovar Typhimurium for at least 20 h postinfection. Transgenic
expression of human defensin 5 in mouse organoids lacking functional murine alpha
defensins partially restored bacterial killing. We also found that organoids from
NOD2(-/-) mice were not impaired in alpha-defensin expression or antibacterial
activity. This model is optimized for the study of non-invasive bacteria but can
be extended to other enteric pathogens and is amenable to further genetic
manipulation of both the host and microbe to dissect this critical interface of
host defense.
PMID- 25118164
TI - A meta-analysis of complications following deceased donor liver transplant.
AB - BACKGROUND: Liver transplantation is a complex surgery associated with high rates
of postoperative complications. While national outcomes data are available,
national rates of most complications are unknown. DATA SOURCES: A systematic
review of the literature reporting rates of postoperative complications between
2002 and 2012 was performed. A cohort of 29,227 deceased donor liver transplant
recipients from 74 studies was used to calculate pooled incidences for 17 major
postoperative complications. CONCLUSIONS: This is the first comprehensive review
of postoperative complications after liver transplantation and can serve as a
guide for transplant and nontransplant clinicians. Efforts to collect national
data on complications, such as through the National Surgical Quality Improvement
Program, would improve the ability to provide patients with informed consent,
serve as a tool for individual center performance monitoring, and provide a
central source against which to measure interventions aimed at improving patient
care.
PMID- 25118166
TI - Type II cytokines impair host defense against an intracellular fungal pathogen by
amplifying macrophage generation of IL-33.
AB - Interleukin (IL)-4 subverts protective immunity to multiple intracellular
pathogens, including the fungus Histoplasma capsulatum. Previously, we reported
that H. capsulatum-challenged CCR2(-/-) mice manifest elevated pulmonary fungal
burden owing to exaggerated IL-4. Paradoxical to our anticipation in IL-33
driving IL-4, we discovered that the latter prompted IL-33 in mutant mice. In
infected CCR2(-/-) animals, amplified IL-33 succeeded the heightened IL-4
response and inhibition of IL-4 signaling decreased IL-33. Moreover, macrophages,
but not epithelial cells or dendritic cells, from these mice expressed higher IL
33 in comparison with controls. Dissection of mechanisms that promulgated IL-33
revealed type-II cytokines and H. capsulatum synergistically elicited an IL-33
response in macrophages via signal transducer and activator of transcription
factor 6/interferon-regulatory factor-4 and Dectin-1 pathways, respectively.
Neutralizing IL-33 in CCR2(-/-) animals, but not controls, enhanced their
resistance to histoplasmosis. Thus we describe a previously unrecognized role for
IL-4 in instigating IL-33 in macrophages. Furthermore, in the presence of
intracellular fungal pathogens, the type-II cytokine-driven IL-33 response
impairs immunity.
PMID- 25118167
TI - In vivo attenuation and genetic evolution of a ST247-SCCmecI MRSA clone after 13
years of pathogenic bronchopulmonary colonization in a patient with cystic
fibrosis: implications of the innate immune response.
AB - Methicillin-resistant Staphylococcus aureus (MRSA) causes chronic pulmonary
infections in patients with cystic fibrosis (CF). This study tracks the 13-year
evolution (1996-2009) of a single MRSA clone in a male patient with CF,
evaluating both the host immunogenic response and the microbial variations. Whole
genome sequencing was performed for the initial (CF-96) and evolved (CF-09)
isolates. The immunogenicity of CF-96 and CF-09 was evaluated by incubation with
innate immune cells from healthy volunteers. We also studied the patient's innate
immune response profile, cytokine production, expression of triggering receptor
expressed on myeloid cells-1 (TREM-1), and phagocytosis. A total of 30 MRSA ST247
SCCmecI-pvl(-) isolates were collected, which evidenced a genome size reduction
from the CF-96 ancestor to the evolved CF-09 strain. Up to six changes in the spa
type were observed over the course of the 13-year evolution. Cytokine production,
TREM-1 expression, and phagocytosis were significantly lower for the healthy
volunteer monocytes exposed to CF-09, compared with those exposed to CF-96.
Patient monocytes exhibited a reduced inflammatory response when challenged with
CF-09. Genetic changes in MRSA, leading to reduced immunogenicity and entry into
the refractory state, may contribute to the attenuation of virulence and
efficient persistence of the bacteria in the CF lung.
PMID- 25118168
TI - Time to onset of pain: effects of magnitude and location for static pressures
applied to the plantar foot.
AB - Mechanisms that cause foot discomfort during prolonged standing are poorly
understood. There is currently no method for evaluating discomfort associated
with low levels of static pressure that are typical during standing. Pain
thresholds were measured for 20 healthy participants by applying five levels of
static pressure at different plantar foot locations. A survival analysis was
performed to determine the effects of pressure magnitude and foot location on the
time until pain onset. Time to pain onset was significantly affected by pressure
magnitude (P < 0.001); time decreased as pressure increased. Foot location was
also significant (P < 0.001); greatest times to pain onset (least sensitive) were
observed under the heel and fifth metatarsal head, shortest times (most
sensitive) were found under the midfoot. This research presents a novel
methodology for evaluating static pressure that may be applicable to product
design.
PMID- 25118170
TI - A cancer cell-activatable aptamer-reporter system for one-step assay of
circulating tumor cells.
AB - The current antibody-mediated numeration assays of circulating tumor cells (CTCs)
require multiple steps and are time-consuming. To overcome these technical
limitations, a cancer cell-activatable aptamer-reporter was formulated by
conjugating a biomarker-specific aptamer sequence with paired fluorochrome
quencher molecules. In contrast to the antibody probes, the intact aptamer
reporter was optically silent in the absence of cells of interest. However, when
used in an assay, the aptamer selectively targeted cancer cells through
interaction with a specific surface biomarker, which triggered internalization of
the aptamer-reporter and, subsequently, into cell lysosomes. Rapid lysosomal
degradation of the aptamer-reporter resulted in separation of the paired
fluorochrome-quencher molecules. The released fluorochrome emitted bright
fluorescent signals exclusively within the targeted cancer cells, with no
background noise in the assay. Thus, the assays could be completed in a single
step within minutes. By using this one-step assay, CTCs in whole blood and marrow
aspirate samples of patients with lymphoma tumors were selectively highlighted
and rapidly detected with no off-target signals from background blood cells. The
development of the cancer cell-activatable aptamer-reporter system allows for the
possibility of a simple and robust point-of-care test for CTC detection, which is
currently unavailable.
PMID- 25118171
TI - Hybrid Nanomaterial Complexes for Advanced Phage-guided Gene Delivery.
AB - Developing nanomaterials that are effective, safe, and selective for gene
transfer applications is challenging. Bacteriophages (phage), viruses that infect
bacteria only, have shown promise for targeted gene transfer applications.
Unfortunately, limited progress has been achieved in improving their potential to
overcome mammalian cellular barriers. We hypothesized that chemical modification
of the bacteriophage capsid could be applied to improve targeted gene delivery by
phage vectors into mammalian cells. Here, we introduce a novel hybrid system
consisting of two classes of nanomaterial systems, cationic polymers and M13
bacteriophage virus particles genetically engineered to display a tumor-targeting
ligand and carry a transgene cassette. We demonstrate that the phage complex with
cationic polymers generates positively charged phage and large aggregates that
show enhanced cell surface attachment, buffering capacity, and improved transgene
expression while retaining cell type specificity. Moreover, phage/polymer
complexes carrying a therapeutic gene achieve greater cancer cell killing than
phage alone. This new class of hybrid nanomaterial platform can advance targeted
gene delivery applications by bacteriophage.
PMID- 25118169
TI - Reduced apolipoprotein glycosylation in patients with the metabolic syndrome.
AB - OBJECTIVE: The purpose of this study was to compare the apolipoprotein
composition of the three major lipoprotein classes in patients with metabolic
syndrome to healthy controls. METHODS: Very low density (VLDL), intermediate/low
density (IDL/LDL, hereafter LDL), and high density lipoproteins (HDL) fractions
were isolated from plasma of 56 metabolic syndrome subjects and from 14 age-sex
matched healthy volunteers. The apolipoprotein content of fractions was analyzed
by one-dimensional (1D) gel electrophoresis with confirmation by a combination of
mass spectrometry and biochemical assays. RESULTS: Metabolic syndrome patients
differed from healthy controls in the following ways: (1) total plasma--apoA1 was
lower, whereas apoB, apoC2, apoC3, and apoE were higher; (2) VLDL--apoB, apoC3,
and apoE were increased; (3) LDL--apoC3 was increased, (4) HDL--associated
constitutive serum amyloid A protein (SAA4) was reduced (p<0.05 vs. controls for
all). In patients with metabolic syndrome, the most extensively glycosylated (di
sialylated) isoform of apoC3 was reduced in VLDL, LDL, and HDL fractions by 17%,
30%, and 25%, respectively (p<0.01 vs. controls for all). Similarly, the
glycosylated isoform of apoE was reduced in VLDL, LDL, and HDL fractions by 15%,
26%, and 37% (p<0.01 vs. controls for all). Finally, glycosylated isoform of SAA4
in HDL fraction was 42% lower in patients with metabolic syndrome compared with
controls (p<0.001). CONCLUSIONS: Patients with metabolic syndrome displayed
several changes in plasma apolipoprotein composition consistent with
hypertriglyceridemia and low HDL cholesterol levels. Reduced glycosylation of
apoC3, apoE and SAA4 are novel findings, the pathophysiological consequences of
which remain to be determined.
PMID- 25118176
TI - Microbial contamination of enteral feeding products in thermoneutral and
hyperthermal ICU environments.
AB - BACKGROUND: Temperature is known to affect bacterial growth, but current safety
recommendations for enteral formula are based on studies conducted in
thermoneutral environments, which are not representative of select burn intensive
care units (ICUs) that are kept therapeutically hyperthermal. This project
evaluated microbial growth in 3 enteral feeding systems: closed, open, and open
with modular additives (modular tube feeding [MTF]) exposed to 2 different
environments. PROCEDURES: Product for each of the 3 systems was prepared and hung
in both a thermoneutral (23.3 degrees C) and a hyperthermal (32.5 degrees C) ICU
room. At baseline, 4 hours, and 8 hours, samples were plated and incubated
overnight and the number of colony-forming units (CFUs) counted. FINDINGS: In the
thermoneutral and hyperthermal environments, there was no evidence of microbial
growth in the open or closed feeding systems at any time point. The MTF exhibited
baseline contamination with a median of 10 CFUs (95% CI, 8-16) and significant
growth over time to 54 CFUs (95% CI, 20-230) by 8 hours in the thermoneutral
setting. In the hyperthermal environment, the MTF showed baseline contamination
of 390 CFUs (95% CI, 40-1600) and significant growth over time, with 30% of
samples exhibiting contamination levels exceeding Food and Drug Administration
standards by 4 hours and CFUs being too numerous to count by 8 hours. CONCLUSION:
CFUs in enteral formula did not differ between open and closed feeding systems in
either environment for up to 8 hours; however, the addition of modulars to open
systems may result in an unacceptable risk of contamination in hyperthermal
environments.
PMID- 25118177
TI - Efficacy and safety of using L-cysteine as a catheter-clearing agent for
nonthrombotic occlusions of central venous catheters in children.
AB - Critically ill pediatric patients, especially in the intensive care unit, receive
multiple medications and have a higher risk of central venous catheter (CVC)
occlusion. If an occlusion occurs immediately after the administration of
multiple medications or incompatible medications, either an acidic solution such
as 0.1 N hydrochloric acid (HCl) or a basic solution of 1 mEq/mL sodium
bicarbonate or 0.1 N sodium hydroxide can be used. However, compounding and
storing of 0.1 N HCl has become more complex due to USP <797> guidelines for
sterile compounding, and an alternative is needed. We report a series of cases in
which L-cysteine was used instead of HCl to clear CVCs occluded due to
administration of multiple medications. L-cysteine is a commercially available,
sterile solution with a pH of 1-2.5. CVC occlusion was resolved in 10 of the 16
episodes in 13 patients. Two of the 16 occlusions were phenytoin related and
would not have responded. An L-cysteine dose of 50 mg was used during 10 of the
16 episodes, 100 mg during 5 episodes, and 25 mg during 1 episode. A correlation
between catheter clearance and dose was not observed. Occlusion resolution due to
L-cysteine was not correlated to the prior use of tissue plasminogen activator.
Metabolic acidosis, adverse effects, or damage to the catheters due to L-cysteine
were not observed. On the basis of this limited experience, we propose L-cysteine
as an effective alternative to 0.1 N HCl for clearing CVC occlusions caused by
drugs with an acidic pKa.
PMID- 25118175
TI - Crystal structure of the RNA-guided immune surveillance Cascade complex in
Escherichia coli.
AB - Clustered regularly interspaced short palindromic repeats (CRISPR) together with
CRISPR-associated (Cas) proteins form the CRISPR/Cas system to defend against
foreign nucleic acids of bacterial and archaeal origin. In the I-E subtype
CRISPR/Cas system, eleven subunits from five Cas proteins (CasA1B2C6D1E1)
assemble along a CRISPR RNA (crRNA) to form the Cascade complex. Here we report
on the 3.05 A crystal structure of the 405-kilodalton Escherichia coli Cascade
complex that provides molecular details beyond those available from earlier lower
resolution cryo-electron microscopy structures. The bound 61-nucleotide crRNA
spans the entire 11-protein subunit-containing complex, where it interacts with
all six CasC subunits (named CasC1-6), with its 5' and 3' terminal repeats
anchored by CasD and CasE, respectively. The crRNA spacer region is positioned
along a continuous groove on the concave surface generated by the aligned CasC1-6
subunits. The five long beta-hairpins that project from individual CasC2-6
subunits extend across the crRNA, with each beta-hairpin inserting into the gap
between the last stacked base and its adjacent splayed counterpart, and
positioned within the groove of the preceding CasC subunit. Therefore, instead of
continuously stacking, the crRNA spacer region is divided into five equal
fragments, with each fragment containing five stacked bases flanked by one
flipped-out base. Each of those crRNA spacer fragments interacts with CasC in a
similar fashion. Furthermore, our structure explains why the seed sequence, with
its outward-directed bases, has a critical role in target DNA recognition. In
conclusion, our structure of the Cascade complex provides novel molecular details
of protein-protein and protein-RNA alignments and interactions required for
generation of a complex mediating RNA-guided immune surveillance.
PMID- 25118178
TI - Cholesterol metabolism is altered in Rett syndrome: a study on plasma and primary
cultured fibroblasts derived from patients.
AB - Rett (RTT) syndrome is a severe neurological disorder that affects almost
exclusively females. Several detectable mutations in the X-linked methyl-CpG
binding protein 2 gene (MECP2) are responsible for the onset of the disease.
MeCP2 is a key transcription regulator involved in gene silencing via methylation
dependent remodeling of chromatin. Recent data highlight that lipid metabolism is
perturbed in brains and livers of MECP2-null male mice. In addition, altered
plasma lipid profile in RTT patients has been observed. Thus, the aim of the work
is to investigate the protein network involved in cholesterol homeostasis
maintenance on freshly isolated fibroblasts and plasma from both RTT and healthy
donors. To this end, protein expression of 3-hydroxy-3methyl glutaryl Coenzyme A
reductase (HMGR), sterol regulatory element binding proteins (SREBPs), low
density lipoprotein receptor (LDLr) and scavenger receptor B-1 (SRB-1) was
assessed in cultured skin fibroblasts from unaffected individuals and RTT
patients. In addition, lipid profile and the abundance of proprotein convertase
subtilisin/kexin type 9 (PCSK9) were analyzed on plasma samples. The obtained
results demonstrate that the main proteins belonging to cholesterol regulatory
network are altered in RTT female patients, providing the proof of principle that
cholesterol metabolism may be taken into account as a new target for the
treatment of specific features of RTT pathology.
PMID- 25118179
TI - Assessment of the neutrophilic antibody-dependent respiratory burst (ADRB)
response to Plasmodium falciparum.
AB - Semi-immunity against Pf malaria is based on a combination of cellular and
humoral immune responses. PMNs and IgGs are considered important components of
this process, but the underlying mechanisms are unclear. We investigated the
neutrophilic ADRB by analyzing the production of ROS in response to Pf antigen
specific IgGs bound to solid-phase immobilized antigens (sADRB) or whole
merozoites (mADRB). We found that the PMN stimulations in each assay were based
on different underlying mechanisms, demonstrating the importance of the assay set
up for the evaluation of antibody-triggered PMN responses. In the sADRB assay,
ROS were produced externally, and by specific blocking of CD32(a)/FcgammaRII(a),
the immediate neutrophilic response was abolished, whereas the removal of
CD16(b)/FcgammaRIII(b) had no substantial effect. The key role of CD32(a) was
confirmed using CD16(b)-deficient PMNs, in which similar changes of neutrophilic
ADRB profiles were recorded after treatment. In the mADRB assay, ROS were
produced almost exclusively within the cell, suggesting that the underlying
mechanism was phagocytosis. This was confirmed using an additional phagocytosis
assay, in which PMNs specifically ingested merozoites opsonized with Ghanaian
plasma IgGs, seven times more often than merozoites opsonized with European
plasma IgGs (P<0.001). Our data show that assay set-ups used to evaluate the
responses of PMNs and perhaps other effector cells must be chosen carefully to
evaluate the appropriate cellular responses. Our robust, stable, and well
characterized methods could therefore be useful in malaria vaccine studies to
analyze the antimalarial effector function of antibodies.
PMID- 25118181
TI - Rheinheimera arenilitoris sp. nov., isolated from seashore sand.
AB - A Gram-stain-negative, non-flagellated, aerobic and ovoid or rod-shaped
bacterium, designated J-MS1(T), was isolated from seashore sand in the South Sea,
South Korea, and subjected to a polyphasic taxonomic study. Strain J-MS1(T) was
found to grow optimally at 30 degrees C and pH 7.0-8.0. Phylogenetic analyses
based on 16S rRNA gene sequences showed that strain J-MS1(T) belonged to the
genus Rheinheimera, clustering coherently with the type strain of Rheinheimera
chironomi and sharing 98.34% sequence similarity. Strain J-MS1(T) exhibited 16S
rRNA gene sequence similarity of 94.26-96.98% to the type strains of the other
species of the genus Rheinheimera. In the phylogenetic trees based on gyrB
sequences, strain J-MS1(T) clustered with the type strain of R. chironomi, with
which it shared the highest sequence similarity (86.97%). Strain J-MS1(T)
contained Q-8 as the predominant ubiquinone and summed feature 3 (C(16:1)omega7c
and/or C(16:1)omega6c), C(16:0) and C(18:1)omega7c as the major fatty acids. The
major polar lipids detected in strain J-MS1(T) and in the type strain of R.
chironomi were phosphatidylglycerol and phosphatidylethanolamine. The DNA G+C
content of strain J-MS1(T) was 49.8 mol% and its mean DNA-DNA relatedness value
with R. chironomi LMG 23818(T) was 12%. Differential phenotypic properties,
together with its phylogenetic and genetic distinctiveness, revealed that strain
J-MS1(T) is separated from recognized species of the genus Rheinheimera. On the
basis of the data presented, strain J-MS1(T) is considered to represent a novel
species of the genus Rheinheimera, for which the name Rheinheimera arenilitoris
sp. nov. is proposed. The type strain is J-MS1(T) ( =KCTC 42112(T) =CECT
8623(T)).
PMID- 25118180
TI - Compact genome of the Antarctic midge is likely an adaptation to an extreme
environment.
AB - The midge, Belgica antarctica, is the only insect endemic to Antarctica, and thus
it offers a powerful model for probing responses to extreme temperatures, freeze
tolerance, dehydration, osmotic stress, ultraviolet radiation and other forms of
environmental stress. Here we present the first genome assembly of an
extremophile, the first dipteran in the family Chironomidae, and the first
Antarctic eukaryote to be sequenced. At 99 megabases, B. antarctica has the
smallest insect genome sequenced thus far. Although it has a similar number of
genes as other Diptera, the midge genome has very low repeat density and a
reduction in intron length. Environmental extremes appear to constrain genome
architecture, not gene content. The few transposable elements present are mainly
ancient, inactive retroelements. An abundance of genes associated with
development, regulation of metabolism and responses to external stimuli may
reflect adaptations for surviving in this harsh environment.
PMID- 25118182
TI - Role of editorial and peer review processes in publication bias: analysis of drug
trials submitted to eight medical journals.
AB - BACKGROUND: Publication bias is generally ascribed to authors and sponsors
failing to submit studies with negative results, but may also occur after
submission. We evaluated whether submitted manuscripts on randomized controlled
trials (RCTs) with drugs are more likely to be accepted if they report positive
results. METHODS: Manuscripts submitted from January 2010 through April 2012 to
one general medical journal (BMJ) and seven specialty journals (Annals of the
Rheumatic Diseases, British Journal of Ophthalmology, Gut, Heart, Thorax,
Diabetologia, and Journal of Hepatology) were included, if at least one study arm
assessed the efficacy or safety of a drug and a statistical test was used to
evaluate treatment effects. Publication status was retrospectively retrieved from
submission systems or provided by journals. Sponsorship and trial results were
extracted from manuscripts and classified according to predefined criteria. Main
outcome measure was acceptance for publication. RESULTS: Of 15,972 manuscripts
submitted, 472 (3.0%) were drug RCTs, of which 98 (20.8%) were published. Among
submitted drug RCTs, 287 (60.8%) had positive and 185 (39.2%) negative results.
Of these, 60 (20.9%) and 38 (20.5%), respectively, were published. Manuscripts on
non-industry trials (n = 213) reported positive results in 138 (64.8%)
manuscripts, compared to 71 (47.7%) on industry-supported trials (n = 149), and
78 (70.9%) on industry-sponsored trials (n = 110). Twenty-seven (12.7%) non
industry trials were published, compared to 27 (18.1%) industry-supported and 44
(40.0%) industry-sponsored trials. After adjustment for other trial
characteristics, manuscripts reporting positive results were not more likely to
be published (OR, 1.00; 95% CI, 0.61 to 1.66). Submission to specialty journals,
sample size, multicentre status, journal impact factor, and corresponding authors
from Europe or US were significantly associated with publication. CONCLUSIONS:
For the selected journals, there was no tendency to preferably publish
manuscripts on drug RCTs that reported positive results, suggesting that
publication bias may occur mainly prior to submission.
PMID- 25118183
TI - Telomerase stimulates ribosomal DNA transcription under hyperproliferative
conditions.
AB - In addition to performing its canonical function, Telomerase Reverse
Transcriptase (TERT) has been shown to participate in cellular processes
independent of telomerase activity. Furthermore, although TERT mainly localizes
to Cajal bodies, it is also present within the nucleolus. Because the nucleolus
is the site of rDNA transcription, we investigated the possible role of
telomerase in regulating RNA polymerase I (Pol I). Here we show that TERT binds
to rDNA and stimulates transcription by Pol I during liver regeneration and Ras
induced hyperproliferation. Moreover, the inhibition of telomerase activity by
TERT- or TERC-specific RNA interference, the overexpression of dominant-negative
TERT, and the application of the telomerase inhibitor imetelstat reduce Pol I
transcription and the growth of tumour cells. In vitro, telomerase can stimulate
the formation of the transcription initiation complex. Our results demonstrate
how non-canonical features of telomerase may direct Pol I transcription in
oncogenic and regenerative hyperproliferation.
PMID- 25118184
TI - Relationship between visuospatial neglect and kinesthetic deficits after stroke.
AB - BACKGROUND: After stroke, visuospatial and kinesthetic (sense of limb motion)
deficits are common, occurring in approximately 30% and 60% of individuals,
respectively. Although both types of deficits affect aspects of spatial
processing necessary for daily function, few studies have investigated the
relationship between these 2 deficits after stroke. OBJECTIVE: We aimed to
characterize the relationship between visuospatial and kinesthetic deficits after
stroke using the Behavioral Inattention Test (BIT) and a robotic measure of
kinesthetic function. METHODS: Visuospatial attention (using the BIT) and
kinesthesia (using robotics) were measured in 158 individuals an average of 18
days after stroke. In the kinesthetic matching task, the robot moved the
participant's stroke-affected arm at a preset direction, speed, and magnitude.
Participants mirror-matched the robotic movement with the less/unaffected arm as
soon as they felt movement in their stroke affected arm. RESULTS: We found that
participants with visuospatial inattention (neglect) had impaired kinesthesia
100% of the time, whereas only 59% of participants without neglect were impaired.
For those without neglect, we observed that a higher percentage of participants
with lower but passing BIT scores displayed impaired kinesthetic behavior (78%)
compared with those participants who scored perfect or nearly perfect on the BIT
(49%). CONCLUSIONS: The presence of visuospatial neglect after stroke is highly
predictive of the presence of kinesthetic deficits. However, the presence of
kinesthetic deficits does not necessarily always indicate the presence of
visuospatial neglect. Our findings highlight the importance of assessment and
treatment of kinesthetic deficits after stroke, especially in patients with
visuospatial neglect.
PMID- 25118185
TI - Recent research on the growth plate: Regulation, bone growth defects, and
potential treatments.
PMID- 25118188
TI - Oculo-auriculo-vertebral spectrum: a review of the literature and genetic update.
AB - Oculo-auriculo-vertebral spectrum (OAVS, OMIM 164 210) is a developmental
disorder primarily involving structures derived from the first and second
pharyngeal arches during embryogenesis. The phenotype is clinically heterogeneous
and is typically characterised by abnormal development of the ear, mandible
anomalies and defects of the vertebral column. OAVS may occur as a multiple
congenital abnormality, and associated findings include anomalies of the eye,
brain, heart, kidneys and other organs and systems. Both genetic and
environmental factors are thought to contribute to this craniofacial condition,
however, the mechanisms are still poorly understood. Here, we present a review of
the literature on OAVS, discussing what is known about the aetiology, candidate
loci, possible mechanisms and the range of clinical features that characterise
this condition. We also comment on some important aspects of recurrence risk
counselling to aid clinical management.
PMID- 25118186
TI - Bright and fast multicoloured voltage reporters via electrochromic FRET.
AB - Genetically encoded fluorescent reporters of membrane potential promise to reveal
aspects of neural function not detectable by other means. We present a palette of
multicoloured brightly fluorescent genetically encoded voltage indicators with
sensitivities from 8-13% DeltaF/F per 100 mV, and half-maximal response times
from 4-7 ms. A fluorescent protein is fused to an archaerhodopsin-derived voltage
sensor. Voltage-induced shifts in the absorption spectrum of the rhodopsin lead
to voltage-dependent nonradiative quenching of the appended fluorescent protein.
Through a library screen, we identify linkers and fluorescent protein
combinations that report neuronal action potentials in cultured rat hippocampal
neurons with a single-trial signal-to-noise ratio from 7 to 9 in a 1 kHz imaging
bandwidth at modest illumination intensity. The freedom to choose a voltage
indicator from an array of colours facilitates multicolour voltage imaging, as
well as combination with other optical reporters and optogenetic actuators.
PMID- 25118187
TI - The association between race and Crohn's disease phenotype in the Western Cape
population of South Africa, defined by the Montreal Classification System.
AB - BACKGROUND: Inter-racial differences in disease characteristics and in the
management of Crohn's disease (CD) have been described in African American and
Asian subjects, however for the racial groups in South Africa, no such recent
literature exists. METHODS: A cross sectional study of all consecutive CD
patients seen at 2 large inflammatory bowel disease (IBD) referral centers in the
Western Cape, South Africa between September 2011 and January 2013 was performed.
Numerous demographic and clinical variables at diagnosis and date of study
enrolment were identified using an investigator administered questionnaire as
well as clinical examination and patient case notes. Using predefined
definitions, disease behavior was stratified as 'complicated' or 'uncomplicated'.
RESULTS: One hundred and ninety four CD subjects were identified; 35 (18%) were
white, 152 (78%) were Cape Coloured and 7(4%) were black. On multiple logistic
regression analysis Cape Coloureds were significantly more likely to develop
'complicated' CD (60% vs. 9%, p = 0.023) during the disease course when compared
to white subjects. In addition, significantly more white subjects had
successfully discontinued cigarette smoking at study enrolment (31% vs. 7%
reduction, p = 0.02). No additional inter-racial differences were found. A low
proportion of IBD family history was observed among the non-white subjects.
CONCLUSIONS: Cape Coloured patients were significantly more likely to develop
'complicated' CD over time when compared to whites.
PMID- 25118189
TI - Does marriage really matter to health? Intra- and inter-country evidence from
China, Japan, Taiwan, and the Republic of Korea.
AB - BACKGROUND: The health benefits of marriage have been demonstrated mainly by
studies on Western populations. This study aims to test whether the benefits are
also valid in East Asian populations. METHODOLOGY/PRINCIPAL FINDINGS: Individuals
(n = 8,538) from China, Japan, Taiwan, and the Republic of Korea were sampled
from the 2006 East Asian Social Survey. The association between self-rated health
status and two marriage-related independent variables was analyzed using
multivariate logistic regression models. In a two-level analysis for individuals
from all countries, married individuals were more likely to report very good or
good health compared to their never-married counterparts [odds ratio (OR) 1.56;
95% confidence interval (95% CI) 1.16-2.10]. However, the addition of marital
satisfaction disintegrated the significant association of marriage with self
rated health. Married individuals in satisfying marriages were more likely to
report very good or good health compared with never-married individuals (OR 1.85;
95% CI 1.37-2.50). In contrast, married individuals in dissatisfying marriages
were as likely to report very good or good health as never-married individuals
(OR 0.78; 95% CI 0.50-1.24). In a one-level analysis for each country, the
importance of marital satisfaction varied greatly across countries. Unlike in
other countries, in Japan, married individuals in dissatisfying marriages were
about half as likely to report very good or good health as never-married
individuals (OR 0.51, 95% CI 0.31-0.83), thereby showing no significant benefits
from marriage with regard to self-rated health. CONCLUSION/SIGNIFICANCE: The
present study of East Asian countries suggests that marital satisfaction is of
greater importance in determining self-rated health than marriage itself, and
that the importance of marital satisfaction varies across countries. Further
research is required to better understand the relationship between marital
satisfaction and self-rated health in different socio-cultural settings, and to
establish effective social policies aiming at improving public health.
PMID- 25118190
TI - Secretory Leukocyte Protease Inhibitor (SLPI): Emerging Roles in CNS Trauma and
Repair.
AB - At first glance, secretory leukocyte protease inhibitor (SLPI) would appear to
have little relevance to the central nervous system (CNS). This serine protease
inhibitor is most commonly found in mucosal fluids such as saliva and is best
known for its anti-inflammatory and antimicrobial properties. It has been shown
to promote wound healing by reducing expression of pro-inflammatory cytokines,
and it can also inhibit bacterial growth and block HIV infection of macrophages.
In the past 10 years, however, several studies have reported that SLPI is
strongly up-regulated in response to CNS injury and that exogenous administration
of SLPI is neuroprotective. It has also been shown that SLPI can overcome
inhibition by CNS myelin and promote axonal regeneration. In this review, we will
discuss these studies, examine the molecular mechanisms underlying SLPI's
effects, and consider SLPI's potential for therapeutic use in cerebral ischemia,
spinal cord injury, and multiple sclerosis.
PMID- 25118191
TI - Endovascular treatment in patients with acute ischemic stroke and apparent
occlusion of the extracranial internal carotid artery on CTA.
AB - BACKGROUND: Intra-arterial treatment is gaining importance in acute ischemic
stroke, but its role in patients with apparent occlusion of the extracranial
internal carotid artery (ICA) on computed tomographic angiography (CTA) is
inconclusive. OBJECTIVE: To review retrospectively the results of intra-arterial
treatment in patients with stroke and apparent extracranial ICA occlusion.
METHODS: In more than 3000 patients with stroke admitted to our institution
during 2008-2013, and the subgroup with suboptimal results after intravenous
thrombolysis (IVT), CTA showed the absence of contrast in the extracranial ICA in
16 patients. Angiography showed true occlusion of the extracranial ICA in 10 and
pseudo-occlusion in 6 patients. Treatment was considered technically successful
when Thrombolysis in Cerebral Infarction scale (TICI) scores improved to 2 or 3
and clinically successful when the National Institutes of Health Stroke Scale
(NIHSS) improved by at least 10 points or a NIHSS score of 0 or 1 was found at
discharge. RESULTS: Recanalization was achieved in 5 of 6 patients with pseudo
occlusions and in 6 of 10 patients with true occlusion of the extracranial ICA.
Favorable clinical outcomes were seen in 3 of 6 patients with pseudo-occlusions
and in 4 of 10 patients with true occlusions. Four patients died, and in these
patients infarction of >15% of the affected hemisphere had been seen on admission
CT. CONCLUSIONS: In cases of acute stroke and apparent occlusion of the
extracranial ICA, intra-arterial treatment should be considered, especially when
IVT fails and <15% of the hemisphere is infarcted on CT. Endovascular treatment
may be beneficial especially in pseudo-occlusions but also in true occlusions of
the extracranial ICA.
PMID- 25118192
TI - Angiographic factors influencing the success of endovascular treatment of
arteriovenous malformations involving the corpus callosum.
AB - OBJECTIVE: Arteriovenous malformations (AVMs) of the corpus callosum are rare
lesions, accounting for 9-11% of brain AVMs. Microsurgical resection of such
lesions is difficult because of their deep location, and also because of possible
neuropsychological disasters resulting from extended callosal resection. The
introduction of endovascular and radiation therapies has fundamentally changed
the outcome of these lesions. METHODS: We prospectively collected clinical and
angiographic data on cerebral AVMs from 1995. We reviewed data from patients
treated for an AVM of the corpus callosum and identified the factors influencing
the endovascular approach of such lesions. RESULTS: 38 patients (mean age 31
years) were consecutively treated by endovascular techniques. 78.9% (30 cases) of
patients presented with intracranial hemorrhage. 15 AVMs (39.5%) were anterior,
18 (47.4%) were posterior, and five (13.1%) were holocallosal. The Spetzler
Martin grade was I in two cases (5.2%), II in 20 cases (52.6%), III in nine cases
(23.7%), IV in six cases (15.8%), and V in one case (2.6%). The nidus was compact
in 19 cases (50%), diffuse in 13 (34.2%), and multifocal in six (15.8%). Both
anterior and posterior circulation branches fed 14 nidi (36.8%). Venous drainage
was superficial in three cases (7.9%), deep in 28 (73.7%), and both in seven
cases (18.4%). 104 sessions were performed, with a procedural complication rate
of 6.7%. Mean follow-up was 43.6 months, with the last modified Rankin Scale
score <3 in 33 cases (86.8%). 22 patients (57.9%) were totally cured. Univariate
analysis of factors influencing the success of endovascular treatment showed that
Spetzler-Martin grade >=3 (p=0.046), nidus >30 mm (p=0.02), extension in an
eloquent area (p=0.03), and holocallosal type (p0.005) significantly diminished
the chances of cure of the AVM. CONCLUSIONS: AVMs of the corpus callosum seems to
be difficult to treat with endovascular therapy alone. The goal of embolization
should be prevention of (re) bleeding and a decrease in nidus size. Our
experience regarding this sub-pathology suggests that a combination of
endovascular therapy and radiotherapy may be the best option.
PMID- 25118193
TI - Balloon-augmented Onyx embolization of cerebral arteriovenous malformations using
a dual-lumen balloon: a multicenter experience.
AB - INTRODUCTION: Conventional Onyx embolization of cerebral arteriovenous
malformations (AVMs) requires lengthy procedure and fluoroscopy times to form an
adequate 'proximal plug' which allows forward nidal penetration while preventing
reflux and non-targeted embolization. We review our experience with balloon
augmented Onyx embolization of cerebral AVMs using a dual-lumen balloon catheter
technique designed to minimize these challenges. METHODS: Retrospectively
acquired data for all balloon-augmented cerebral AVM embolizations performed
between 2011 and 2014 were obtained from four tertiary care centers. For each
procedure, at least one Scepter C balloon catheter was advanced into the AVM
arterial pedicle of interest and Onyx embolization was performed through the
inner lumen after balloon inflation via the outer lumen. RESULTS: Twenty patients
underwent embolization with the balloon-augmented technique over 24 discreet
treatment episodes. There were 37 total arterial pedicles embolized with the
balloon-augmented technique, a mean of 1.9 per patient (range 1-5). The treated
AVMs were heterogeneous in their location and size (mean 3.3+/-1.6 cm). Mean
fluoroscopy time for each procedure was 48+/-26 min (28 min per embolized
pedicle). Two Scepter C balloon catheter-related complications (8.3% of
embolization sessions, 5.4% of pedicles embolized) were observed: an
intraprocedural rupture of a feeding pedicle and fracture and retention of a
catheter fragment. CONCLUSIONS: This multicenter experience represents the
largest reported series of balloon-augmented Onyx embolization of cerebral AVMs.
The technique appears safe and effective in the treatment of AVMs, allowing more
efficient and controlled injection of Onyx with a decreased risk of reflux and
decreased fluoroscopy times.
PMID- 25118194
TI - A high-density genetic map for soybean based on specific length amplified
fragment sequencing.
AB - Soybean is an important oil seed crop, but very few high-density genetic maps
have been published for this species. Specific length amplified fragment
sequencing (SLAF-seq) is a recently developed high-resolution strategy for large
scale de novo discovery and genotyping of single nucleotide polymorphisms. SLAF
seq was employed in this study to obtain sufficient markers to construct a high
density genetic map for soybean. In total, 33.10 Gb of data containing
171,001,333 paired-end reads were obtained after preprocessing. The average
sequencing depth was 42.29 in the Dongnong594, 56.63 in the Charleston, and 3.92
in each progeny. In total, 164,197 high-quality SLAFs were detected, of which
12,577 SLAFs were polymorphic, and 5,308 of the polymorphic markers met the
requirements for use in constructing a genetic map. The final map included 5,308
markers on 20 linkage groups and was 2,655.68 cM in length, with an average
distance of 0.5 cM between adjacent markers. To our knowledge, this map has the
shortest average distance of adjacent markers for soybean. We report here a high
density genetic map for soybean. The map was constructed using a recombinant
inbred line population and the SLAF-seq approach, which allowed the efficient
development of a large number of polymorphic markers in a short time. Results of
this study will not only provide a platform for gene/quantitative trait loci fine
mapping, but will also serve as a reference for molecular breeding of soybean.
PMID- 25118195
TI - Long-term sinonasal outcomes of aspirin desensitization in aspirin exacerbated
respiratory disease.
AB - OBJECTIVE: This study aimed to assess sinonasal outcomes in patients with aspirin
exacerbated respiratory disease (AERD) undergoing aspirin desensitization
following endoscopic sinus surgery (ESS). STUDY DESIGN: Case series with chart
review. SETTING: University hospital. SUBJECTS AND METHODS: A retrospective
review of sinonasal outcomes was conducted for 30 AERD patients undergoing
aspirin desensitization and maintenance therapy following ESS. Sinonasal outcomes
were prospectively assessed by the Sinonasal Outcomes Test-22 (SNOT-22) and
endoscopic polyp grading system. Data were collected preoperatively, 1 and 4
weeks postsurgery (before desensitization), and 1, 6, 12, 18, 24, and 30 months
after aspirin desensitization. RESULTS: Twenty-eight of 30 patients (93.3%)
successfully completed aspirin desensitization, whereas 2 of 30 (6.7%) were
unable to complete desensitization due to respiratory intolerance. Of the 21
patients who successfully completed a minimum of 24 weeks of follow-up, 20
(95.2%) patients demonstrated sustained endoscopic and symptomatic improvement
for a median follow-up period of 33 months. After surgical treatment but before
desensitization, patients experienced significant reductions in SNOT-22 and polyp
grade scores. In the first 6 months after aspirin desensitization, patients
experienced further significant reductions in SNOT-22 scores, whereas polyp grade
remained stable. The improvements in symptom endoscopic scores were preserved
throughout the follow-up period after desensitization. No patients required
additional sinus surgery. One patient had to discontinue aspirin therapy due to
gastrointestinal side effects. No other adverse reactions to aspirin were noted.
CONCLUSION: Aspirin desensitization following ESS appears to be a well-tolerated
and effective adjunctive therapy for long-term control of nasal polyposis in
patients with AERD.
PMID- 25118196
TI - Rapid identification of a novel complex I MT-ND3 m.10134C>A mutation in a Leigh
syndrome patient.
AB - Leigh syndrome (LS) is a rare progressive multi-system neurodegenerative
disorder, the genetics of which is frequently difficult to resolve. Rapid
determination of the genetic etiology of LS in a 5-year-old girl facilitated
inclusion in Edison Pharmaceutical's phase 2B clinical trial of EPI-743. SNP
arrays and high-coverage whole exome sequencing were performed on the proband,
both parents and three unaffected siblings. Subsequent multi-tissue targeted high
depth mitochondrial sequencing was performed using custom long-range PCR
amplicons. Tissue-specific mutant load was also assessed by qPCR. Complex I was
interrogated by spectrophotometric enzyme assays and Western Blot. No putatively
causal mutations were identified in nuclear-encoded genes. Analysis of low
coverage off-target mitochondrial reads revealed a previously unreported
mitochondrial mutation in the proband in MT-ND3 (m.10134C>A, p.Q26K), a Complex I
mitochondrial gene previously associated with LS. Targeted investigations
demonstrated that this mutation was 1% heteroplasmic in the mother's blood and
homoplasmic in the proband's blood, fibroblasts, liver and muscle. Enzyme assays
revealed decreased Complex I activity. The identification of this novel LS MT-ND3
variant, the genomics of which was accomplished in less than 3.5 weeks, indicates
that rapid genomic approaches may prove useful in time-sensitive cases with an
unresolved genetic diagnosis.
PMID- 25118198
TI - Features of an alternative hemodialysis method using a hemoconcentrator during
cardiopulmonary bypass surgeries.
AB - PURPOSE: This study clarified the features of a hemoconcentrator-based,
alternative hemodialysis (ALTHD) method that improves the speed of serum
potassium (K(+)) concentration adjustments, compared with dilutional
ultrafiltration (DUF), during cardiopulmonary bypasses. METHODS: Standardized
bovine blood was recirculated (300 ml/min) through an in vitro hemoconcentrator
circuit; hematocrit, K(+) and glucose levels were measured at 5-20 min after DUF
or ALTHD. We evaluated DUF at dialysis speeds of 50-250 ml/min and ALTHD at
speeds of 50-1000 ml/min. RESULTS: ALTHD rapidly corrected K(+) and glucose
concentrations at speeds up to 800 ml/min. ALTHD took 8.9 min to reach a K(+)
level of 4.5 mmol/L, faster than DUF (12.8 min). The ALTHD efficiency curves
plateaued at 600 ml/min. CONCLUSION: ALTHD allowed faster adjustment of
electrolyte levels, with peak efficiency at 600 ml/min. ALTHD has possible
clinical application if available for potential use during all cardiopulmonary
bypass surgeries involving extracorporeal circulation.
PMID- 25118197
TI - What is the incidence of patients with palliative care needs presenting to the
Emergency Department? a critical review.
AB - BACKGROUND: Given the context of ageing populations globally, there are a growing
number of patients with chronic conditions, some of whom are in the final stages
of their disease trajectory, presenting to Emergency Departments. AIM: The aim
was to estimate the incidence of patients with palliative care needs presenting
to the department. METHODS: Three databases (MEDLINE, CINAHL and Embase) were
systematically searched up to August 2012. The reference lists of included
articles were searched as well as Google and Google Scholar. Only studies in
English were included. Two reviewers independently reviewed studies at the
abstract and full-body stages. A critical review using systematic methods was
undertaken as statistical analysis could not be done because of a lack of
information. RESULTS: Only 10 of 1427 identified records met the inclusion
criteria. Different definitions of palliative care were evident. One article
provided an incidence density for patients with non-small cell lung cancer, and
we calculated the mean presentations to be 52.5 per 100 person-months. Two
articles focussed on patients known to palliative care services; we estimated
that 2.5 in 1000 Emergency Department visits were made by these patients. The
review demonstrated that the studies were so different it was not possible to
compare the data. CONCLUSION: There is an absence of evidence regarding the
incidence of patients with palliative care needs presenting to the Emergency
Department. Further research needs to be undertaken in this area to ensure both
clinicians and policymakers have sufficient information for service provision.
PMID- 25118200
TI - Increasing health examination survey participation rates by SMS reminders and
flexible examination times.
AB - AIMS: Declining participation rates are an increasing problem in population
surveys. Different kinds of methods have been used to ensure participation rates
as high as possible. Monetary incentives and reminders have been found to be
effective ways to increase participation rates, but these are rather expensive to
implement in large population surveys. There is a need for cheaper ways to
motivate survey invitees to participate. METHODS: The Kuusamo Health Examination
Survey was conducted in May-June 2011. A random sample of 250 people was selected
for the survey. Mobile phone numbers, when available, were obtained for people
within the sample. For a random sample of 50% of survey invitees with a mobile
phone number, a short message service (SMS) reminder was sent prior to their
appointment. All survey participants were asked to fill in a feedback
questionnaire. RESULTS: Participation rate was 58% for men and 74% for women.
Mobile phone numbers were available for 66% of the sample. Among those receiving
an SMS reminder about their appointment, participation rates were up to 25
percentage points higher than among the group not receiving a reminder. In the
feedback questionnaire, 9% of the survey participants reported that they would
not have participated without the SMS reminder they received. Participants
preferred morning hours and Monday-Tuesday as time and day options for the
examinations. CONCLUSIONS: SMS reminder about the appointment time was an
effective way to increase participation rate, especially among the youngest age
groups also, providing flexible office hours for the examination clinic may
increase participation rate.
PMID- 25118199
TI - The relationship of green space, depressive symptoms and perceived general health
in urban population.
AB - AIMS: To assess the relationship between green space proximity, use of green
space and depressive symptoms and perceived general health among a random sample
men and women. METHODS: Cross-sectional study of a population-based sample of
6,944 45-72 year old Kaunas city residents. Self-reported questionnaires provided
information on sociodemographic variables, health behaviours, depressive symptoms
and poor and very poor perceived general health. Residential proximity to green
spaces was defined as living less than 300 m, within interval of 300-999 m, and
equal or more than 1 km from a park. The use of the park was divided into two
categories: no park use or use <4hrs/week and use of the park >=4 h/week. The
study received approval from the Kaunas Regional Research Ethics Committee.
Multiple logistic regression assessed the associations controlling for
confounding variables. RESULTS: The prevalence of depressive symptoms and poor
and or very poor perceived general health was higher in women than in men. The
association between the use of the park and residential proximity to the park
revealed that women living >300 m from a green space and who used the space >=4
h/week showed higher odds 1.92 (1.11-3.3) and 1.68 (0.81-3.48) of depressive
symptoms and poor and very poor perceived general health as compared to those who
used the park <4 hrs/week and residential proximity was >300 m. CONCLUSIONS: The
results of our study confirmed an association between use of the green space,
residential proximity, and depressive symptoms and poor and very poor perceived
general health among women only.
PMID- 25118202
TI - Endoscopy-Assisted Total Mastectomy Followed by Immediate Pedicled Transverse
Rectus Abdominis Musculocutaneous (TRAM) Flap Reconstruction: Preliminary Results
of 48 Patients.
AB - BACKGROUND: Endoscopy-assisted breast surgery performed through minimal axillary
and/or periareolar incisions is a viable option for patients with breast cancer.
In this study, we report the preliminary results of patients with breast cancer
who underwent endoscopy-assisted total mastectomy (EATM) followed immediately by
pedicled transverse abdominis musculocutaneous (TRAM) flap reconstruction.
METHODS: Patients in this study comprised women with breast cancer who received
EATM and pedicled TRAM flap reconstruction. Clinicopathologic characteristics,
type of surgery, complications, and rate of recurrence were recorded. The
cosmetic outcomes were evaluated objectively by the surgeons and subjectively by
the patients at 3-month postoperative follow-up. RESULTS: A total of 48 patients
underwent 49 EATM procedures followed by pedicled TRAM flap reconstruction. Of
them, 79.6% underwent endoscopic-assisted nipple-sparing mastectomy and 20.4%
received endoscopic-assisted skin-sparing mastectomy. The types of cancer among
these patients included ductal carcinoma in situ in 34.7%, stage I cancer in
36.7%, stage II cancer in 24.5%, and stage IIIa cancer in 4.1% patients. Mean
tumor size was 2.1 +/- 1.4 cm. There were no cases of flap failure. Partial
nipple areolar complex ischemia/necrosis occurred in 4 (10.3%) patients; however,
all cases resolved after conservative treatment. In the aesthetic outcome
evaluation, EATM + TRAM were associated with 89.8% good, 8.2% fair, and 2%
unsatisfactory result. No local recurrence was observed during the follow-up
period. CONCLUSION: EATM followed immediately by pedicled TRAM flap
reconstruction is a safe procedure and results in good cosmetic outcome in women
with early-stage breast cancer.
PMID- 25118204
TI - Back to the basis: breast cancer heterogeneity from an etiological perspective.
PMID- 25118205
TI - Motion sickness in migraine and vestibular disorders.
PMID- 25118206
TI - A diagnostic flow chart for POLG-related diseases based on signs sensitivity and
specificity.
AB - OBJECTIVE: Diseases due to mutations of POLG gene, encoding the mitochondrial DNA
polymerase, are reputed to have very diverse clinical presentations and have been
proposed to cause up to 25% adult mitochondrial diseases. Our objective was the
evaluation of the specificity and sensitivity of the signs encountered with POLG
mutations. DESIGN: Forty-four patients out of 154 with sequenced POLG gene had
mutations affecting either one (POLG(+/-) group) or two POLG alleles (POLG(+/+)
group). Phenotyping included clinical signs, electroneuromyography and brain
imaging while mitochondrial investigations encompassed muscle histochemistry,
respiratory chain assays and search for multiple mitochondrial deletions. The
specificity and sensitivity of the signs associated with POLG mutations were
analysed by comparison between POLG(+/+) and patients without POLG mutation.
RESULTS: High sensitivity but low specificity was observed with single signs such
as axonal sensory neuropathy, cerebellar syndrome, movement disorders and
weakness involving ocular, pharyngeal, axial and/or limb muscles. Specificity was
increased with combination of previous signs plus psychiatric symptoms, cognitive
impairment and epilepsy. High specificity and sensitivity was only obtained with
sensory neuronopathy associated with one of the following signs: weakness of
ocular, pharyngeal, axial and/or limb muscles. Mitochondrial investigations did
not suffice for diagnosis. The widespread neuromuscular signs were often present
since disease onset and were the rule above 50 years of age leading to a very low
probability of POLG mutations in patients with less than three signs and absent
sensory neuropathy. CONCLUSIONS: Phenotypes associated with POLG mutations follow
a reproducible pattern, which allows establishing a diagnostic flow chart.
PMID- 25118208
TI - Simple prognostic model for patients with advanced cancer based on performance
status.
AB - PURPOSE: Providing survival estimates is important for decision making in
oncology care. The purpose of this study was to provide survival estimates for
outpatients with advanced cancer, using the Eastern Cooperative Oncology Group
(ECOG), Palliative Performance Scale (PPS), and Karnofsky Performance Status
(KPS) scales, and to compare their ability to predict survival. METHODS: ECOG,
PPS, and KPS were completed by physicians for each new patient attending the
Princess Margaret Cancer Centre outpatient Oncology Palliative Care Clinic (OPCC)
from April 2007 to February 2010. Survival analysis was performed using the
Kaplan-Meier method. The log-rank test for trend was employed to test for
differences in survival curves for each level of performance status (PS), and the
concordance index (C-statistic) was used to test the predictive discriminatory
ability of each PS measure. RESULTS: Measures were completed for 1,655 patients.
PS delineated survival well for all three scales according to the log-rank test
for trend (P < .001). Survival was approximately halved for each worsening
performance level. Median survival times, in days, for each ECOG level were: EGOG
0, 293; ECOG 1, 197; ECOG 2, 104; ECOG 3, 55; and ECOG 4, 25.5. Median survival
times, in days, for PPS (and KPS) were: PPS/KPS 80-100, 221 (215); PPS/KPS 60 to
70, 115 (119); PPS/KPS 40 to 50, 51 (49); PPS/KPS 10 to 30, 22 (29). The C
statistic was similar for all three scales and ranged from 0.63 to 0.64.
CONCLUSION: We present a simple tool that uses PS alone to prognosticate in
advanced cancer, and has similar discriminatory ability to more complex models.
PMID- 25118209
TI - Cancer survivors: a look backward and forward.
PMID- 25118203
TI - How many etiological subtypes of breast cancer: two, three, four, or more?
AB - Breast cancer is a heterogeneous disease, divisible into a variable number of
clinical subtypes. A fundamental question is how many etiological classes
underlie the clinical spectrum of breast cancer? An etiological subtype reflects
a grouping with a common set of causes, whereas a clinical subtype represents a
grouping with similar prognosis and/or prediction. Herein, we review the evidence
for breast cancer etiological heterogeneity. We then evaluate the etiological
evidence with mRNA profiling data. A bimodal age distribution at diagnosis with
peak frequencies near ages 50 and 70 years is a fundamental characteristic of
breast cancer for important tumor features, clinical characteristics, risk factor
profiles, and molecular subtypes. The bimodal peak frequencies at diagnosis
divide breast cancer overall into a "mixture" of two main components in varying
proportions in different cancer populations. The first breast cancer tends to
arise early in life with modal age-at-diagnosis near 50 years and generally
behaves aggressively. The second breast cancer occurs later in life with modal
age near 70 years and usually portends a more indolent clinical course. These
epidemiological and molecular data are consistent with a two-component mixture
model and compatible with a hierarchal view of breast cancers arising from two
main cell types of origin. Notwithstanding the potential added value of more
detailed categorizations for personalized breast cancer treatment, we suggest
that the development of better criteria to identify the two proposed etiologic
classes would advance breast cancer research and prevention.
PMID- 25118210
TI - Pioneering quality assessment in European cancer centers: a data analysis of the
organization for European cancer institutes accreditation and designation
program.
AB - PURPOSE: In order to improve the quality of care in Cancer Centers (CC) and
designate Comprehensive Cancer Centers (CCCs), the Organization for European
Cancer Institutes (OECI) launched an Accreditation and Designation (A&D) program.
The program facilitates the collection of defined data and the assessment of
cancer center quality. This study analyzes the results of the first 10 European
centers that entered the program. METHODS: The assessment included 927 items
divided across qualitative and quantitative questionnaires. Data collected during
self-assessment and peer-review from the 10 first participating centers were
combined in a database for comparative analysis using simple statistics.
Quantitative and qualitative results were validated by auditors during the peer
review visits. RESULTS: Volumes of various functions and activities dedicated to
care, research, and education varied widely among centers. There were no
significant differences in resources for radiology, radiotherapy, pathologic
diagnostic, and surgery. Differences were observed in the use of clinical
pathways but not for the practices of holding multidisciplinary team meetings and
conforming to guidelines. Regarding human resources, main differences were in the
composition and number of supportive care and research staff. All 10 centers
applied as CCCs; five obtained the label, and five were designated as CCs.
CONCLUSION: The OECI A&D program allows comparisons between centers with regard
to management, research, care, education, and designation as CCs or CCCs. Through
the peer review system, recommendations for improvements are given. Assessing the
added value of the program, as well as research and patient treatment outcomes,
is the next step.
PMID- 25118207
TI - 20 years of leptin: leptin and reproduction: past milestones, present
undertakings, and future endeavors.
AB - The association between leptin and reproduction originated with the leptin
mediated correction of sterility in ob/ob mice and initiation of reproductive
function in normal female mice. The uncovering of a central leptin pathway
regulating food intake prompted the dissection of neuroendocrine mechanisms
involving leptin in the metabolic control of reproduction. The absence of leptin
receptors on GnRH neurons incited a search for intermediary neurons situated
between leptin-responsive and GnRH neurons. This review addresses the most
significant findings that have furthered our understanding of recent progress in
this new field. The role of leptin in puberty was impacted by the discovery of
neurons that co-express kisspeptin, neurokinin B, and dynorphin and these could
act as leptin intermediates. Furthermore, the identification of first-order
leptin-responsive neurons in the premammilary ventral nucleus and other brain
regions opens new avenues to explore their relationship to GnRH neurons. Central
to these advances is the unveiling that agouti-related protein/neuropeptide Y
neurons project onto GnRH and kisspeptin neurons, allowing for a crosstalk
between food intake and reproduction. Finally, while puberty is a state of leptin
sensitivity, mid-gestation represents a state of leptin resistance aimed at
building energy stores to sustain pregnancy and lactation. The mechanisms
underlying leptin resistance in pregnancy have lagged; however, the establishment
of this natural state is significant. Reproduction and energy balance are tightly
controlled and backed up by redundant mechanisms that are critical for the
survival of our species. It will be the goal of the following decade to shed new
light on these complex and essential pathways.
PMID- 25118216
TI - Development of an anti-claudin-3 and -4 bispecific monoclonal antibody for cancer
diagnosis and therapy.
AB - Most malignant tumors are derived from epithelium, and claudin (CLDN)-3 and CLDN
4 are frequently overexpressed in such tumors. Although antibodies have potential
in cancer diagnostics and therapy, development of antibodies against CLDNs has
been difficult because the extracellular domains of CLDNs are too small and there
is high homology among human, rat, and mouse sequences. Here, we created a
monoclonal antibody that recognizes human CLDN-3 and CLDN-4 by immunizing rats
with a plasmid vector encoding human CLDN-4. A hybridoma clone that produced a
rat monoclonal antibody recognizing both CLDN-3 and -4 (clone 5A5) was obtained
from a hybridoma screen by using CLDN-3- and -4-expressing cells; 5A5 did not
bind to CLDN-1-, -2-, -5-, -6-, -7-, or -9-expressing cells. Fluorescence
conjugated 5A5 injected into xenograft mice bearing human cancer MKN74 or LoVo
cells could visualize the tumor cells. The human-rat chimeric IgG1 monoclonal
antibody (xi5A5) activated FcgammaRIIIa in the presence of CLDN-3- or -4
expressing cells, indicating that xi5A5 may exert antibody-dependent cellular
cytotoxicity. Administration of xi5A5 attenuated tumor growth in xenograft mice
bearing MKN74 or LoVo cells. These results suggest that 5A5 shows promise in the
development of a diagnostic and therapeutic antibody for cancers.
PMID- 25118217
TI - Modulation of resistance artery tone by the trace amine beta-phenylethylamine:
dual indirect sympathomimetic and alpha1-adrenoceptor blocking actions.
AB - The trace amine beta-phenylethylamine (PEA) is normally present in the body at
low nanomolar concentrations but can reach micromolar levels after ingestion of
drugs that inhibit monoamine oxidase and primary amine oxidase. In vivo, PEA
elicits a robust pressor response, but there is no consensus regarding the
underlying mechanism, with both vasodilation and constriction reported in
isolated blood vessels. Using functional and biochemical approaches, we found
that at low micromolar concentrations PEA (1-30 MUM) enhanced nerve-evoked
vasoconstriction in the perfused rat mesenteric bed but at a higher concentration
(100 MUM) significantly inhibited these responses. The alpha2-adrenoceptor
antagonist rauwolscine (1 uM) also enhanced nerve-mediated vasoconstriction, but
in the presence of both rauwolscine (1 uM) and PEA (30 uM) together, nerve-evoked
responses were initially potentiated and then showed time-dependent rundown. PEA
(10 and 100 MUM) significantly increased noradrenaline outflow from the
mesenteric bed as determined by high-pressure liquid chromatography coupled with
electrochemical detection. In isolated endothelium-denuded arterial segments, PEA
(1 uM to 1 mM) caused concentration-dependent reversal of tone elicited by the
alpha1-adrenoceptor agonists noradrenaline (EC50 51.69 +/- 10.8 MUM; n = 5),
methoxamine (EC50 68.21 +/- 1.70 MUM; n = 5), and phenylephrine (EC50 67.74 +/-
16.72 MUM; n = 5) but was ineffective against tone induced by prostaglandin F2
alpha or U46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxyprostaglandin F2 alpha).
In rat brain homogenates, PEA displaced binding of both [(3)H]prazosin (Ki ~ 25
MUM) and [(3)H]rauwolscine (Ki ~ 1.2 MUM), ligands for alpha1- and alpha2
adrenoceptors, respectively. These data provide the first demonstration that dual
indirect sympathomimetic and alpha1-adrenoceptor blocking actions underlie the
vascular effects of PEA in resistance arteries.
PMID- 25118218
TI - Views and experiences of the NHS Health Check provided by general medical
practices: cross-sectional survey in high-risk patients.
AB - BACKGROUND: Since the NHS Health Check programme was initiated in 2009, no survey
has sought patients' views of Checks provided by GP practices and few studies
have reported views of the wider public. This study sought the views and
experiences of patients with potentially high-cardiovascular disease (CVD) risk.
METHODS: Cross-sectional postal survey of all the patients with an actual or
estimated CVD risk score of at least 20% over 10 years, registered with 16
general practices in Sefton, North West England, with no follow-up. RESULTS: The
response rate was 23.4% (644/2958), 67.4% had attended and 73.8% of those not yet
invited indicated willingness to attend. Both groups had positive views towards
Health Checks, but more non-attenders agreed these should only be performed by
doctors. Attenders had better self-reported health and healthy lifestyle than non
attenders. Overall 86.6% of attenders recalled receiving one or more pieces of
lifestyle advice and 71.0% claimed to have made at least one lifestyle change;
however, perception and understanding of CVD risk appeared limited. CONCLUSION:
Both attenders and non-attenders had positive views towards NHS Health Checks in
general practice and resultant self-reported lifestyle change in attenders was
high. Clearer written information and explanation of personal CVD risk are
required.
PMID- 25118220
TI - Accidental diagnosis: Aeromonas infection leading to discovery of acute myeloid
leukemia with meylodysplastic syndrome.
AB - PATIENT: 47-year-old African American man. CHIEF COMPLAINT: Initially, serious
finger abscess. The patient reported severe pain that was localized to that
finger only. HISTORY OF PRESENT ILLNESS: His finger had become sore and then
progressively more painful and swollen. PAST MEDICAL HISTORY: A few weeks
earlier, the patient had had a similar abscess on his leg; he could not recall
any specific injuries other than this. He had a past history of epilepsy that is
totally unrelated to this case; he had not had any episodes in more than 10
years. Otherwise, the medical history of the patient was relatively healthy: he
is a nonsmoker with no history of diabetes or steroid use. SOCIAL HISTORY:
Patient washed cars for a living. FAMILY HISTORY: Noncontributory. PHYSICAL
EXAMINATION: Initially, the patient was sent home with a course of antibiotics
(cephalexin and trimethoprim/sulfamethoxazole) and was asked to return to the
hospital for follow up within two days. By the time of the follow-up visit, the
antibiotic treatment had been unsuccessful, and the patient experienced more pain
in the finger; the flesh of the finger was becoming black and necrotic. The
patient tested positive for all myeloid markers: myeloperoxidase (MPO), CD34,
CD33, CD13, CD45, human leukocyte antigen-DR subregion (HLA-DR), CD15, and CD11c.
Trilinear dysplasia was indicated by the results of bone-marrow studies and
peripheral blood smear testing.
PMID- 25118219
TI - Smoking patterns in Great Britain: the rise of cheap cigarette brands and roll
your own (RYO) tobacco.
AB - BACKGROUND: In Britain, the tobacco industry segments cigarettes into four price
categories-premium, mid-price, economy and ultra-low-price (ULP). Our previous
work shows that tobacco companies have kept ULP prices stable in real terms. Roll
your own (RYO) tobacco remains cheaper still. METHODS: Analysis of 2001-08
General Household Survey data to examine trends in use of these cheap products
and, using logistic regression, the profile of users of these products. RESULTS:
Among smokers, the proportion using cheap products (economy, ULP and RYO
combined) increased significantly in almost all age groups and geographic areas.
Increases were most marked in under 24 year olds, 76% of whom smoked cheap
cigarettes by 2008. All cheap products were more commonly used in lower socio
economic groups. Men and younger smokers were more likely to smoke RYO while
women smoked economy brands. Smokers outside London and the South East of England
were more likely to smoke some form of cheap tobacco even once socio-economic
differences were accounted for. CONCLUSIONS: This paper demonstrates that cheap
tobacco use is increasing among young and disadvantaged smokers compromising
declines in population smoking prevalence. Thus, tobacco industry pricing appears
to play a key role in explaining smoking patterns and inequalities in smoking.
PMID- 25118225
TI - The PROMIS smoking assessment toolkit--background and introduction to supplement.
AB - INTRODUCTION: The PROMIS Smoking Initiative has developed an assessment toolkit
for measuring 6 domains of interest to cigarette smoking research: nicotine
dependence, coping expectancies, emotional and sensory expectancies, health
expectancies, psychosocial expectancies, and social motivations for smoking. The
papers in this supplement describe the methods used to develop these item banks,
their psychometric properties, and the preliminary evidence for their validity.
This commentary is meant to provide background information for the material in
this supplement. METHODS: After discussing the use of item response theory in
behavioral measurement, I will briefly review the initial developmental steps for
the smoking assessment toolkit. Finally, I will describe the contents of this
supplement and provide some closing remarks. RESULTS: Psychometric evidence
strongly supports the utility of the toolkit of item banks, short forms (SFs),
and computer adaptive tests (CATs). The item banks for daily smokers produce
scores with reliability estimates above 0.90 for a wide range of each cigarette
smoking domain continuum, and SF and CAT administrations also achieve high
reliability (generally greater than 0.85) using very few items (4-7 items for
most banks). Performance of the banks for nondaily smokers is similar.
Preliminary evidence supports the concurrent and the discriminant validity of the
bank domains. CONCLUSIONS: The new smoking assessment toolkit has attractive
measurement features that are likely to benefit smoking research as researchers
begin to utilize this resource. Information about the toolkit and access to the
assessments is available at the project Web site
(http://www.rand.org/health/projects/promis-smoking-initiative.html) and can also
be accessed via the PROMIS Assessment Center (www.assessmentcenter.net).
PMID- 25118226
TI - Development of the PROMIS nicotine dependence item banks.
AB - INTRODUCTION: Nicotine dependence is a core construct important for understanding
cigarette smoking and smoking cessation behavior. This article describes analyses
conducted to develop and evaluate item banks for assessing nicotine dependence
among daily and nondaily smokers. METHODS: Using data from a sample of daily (N =
4,201) and nondaily (N =1,183) smokers, we conducted a series of item factor
analyses, item response theory analyses, and differential item functioning
analyses (according to gender, age, and race/ethnicity) to arrive at a
unidimensional set of nicotine dependence items for daily and nondaily smokers.
We also evaluated performance of short forms (SFs) and computer adaptive tests
(CATs) to efficiently assess dependence. RESULTS: A total of 32 items were
included in the Nicotine Dependence item banks; 22 items are common across daily
and nondaily smokers, 5 are unique to daily smokers, and 5 are unique to nondaily
smokers. For both daily and nondaily smokers, the Nicotine Dependence item banks
are strongly unidimensional, highly reliable (reliability = 0.97 and 0.97,
respectively), and perform similarly across gender, age, and race/ethnicity
groups. SFs common to daily and nondaily smokers consist of 8 and 4 items
(reliability = 0.91 and 0.81, respectively). Results from simulated CATs showed
that dependence can be assessed with very good precision for most respondents
using fewer than 6 items adaptively selected from the item banks. CONCLUSIONS:
Nicotine dependence on cigarettes can be assessed on the basis of these item
banks via one of the SFs, by using CATs, or through a tailored set of items
selected for a specific research purpose.
PMID- 25118227
TI - Development of the PROMIS coping expectancies of smoking item banks.
AB - OBJECTIVE: Smoking is a coping strategy for many smokers who then have difficulty
finding new ways to cope with negative affect when they quit. This paper
describes analyses conducted to develop and evaluate item banks for assessing the
coping expectancies of smoking for daily and nondaily smokers. METHODS: Using
data from a large sample of daily (N = 4,201) and nondaily (N = 1,183) smokers,
we conducted a series of item factor analyses, item response theory analyses, and
differential item functioning (DIF) analyses (according to gender, age, and
ethnicity) to arrive at a unidimensional set of items for daily and nondaily
smokers. We also evaluated performance of short forms (SFs) and computer adaptive
tests (CATs) for assessing coping expectancies of smoking. RESULTS: For both
daily and nondaily smokers, the unidimensional Coping Expectancies item banks (21
items) are relatively DIF free and are highly reliable (0.96 and 0.97,
respectively). A common 4-item SF for daily and nondaily smokers also showed good
reliability (0.85). Adaptive tests required an average of 4.3 and 3.7 items for
simulated daily and nondaily respondents, respectively, and achieved
reliabilities of 0.91 for both when the maximum test length was 10 items.
CONCLUSIONS: This research provides a new set of items that can be used to
reliably assess coping expectancies of smoking, through a SF, CAT, or a tailored
set selected for a specific research purpose.
PMID- 25118228
TI - Development of the PROMIS positive emotional and sensory expectancies of smoking
item banks.
AB - INTRODUCTION: The positive emotional and sensory expectancies of cigarette
smoking include improved cognitive abilities, positive affective states, and
pleasurable sensorimotor sensations. This paper describes development of Positive
Emotional and Sensory Expectancies of Smoking item banks that will serve to
standardize the assessment of this construct among daily and nondaily cigarette
smokers. METHODS: Data came from daily (N = 4,201) and nondaily (N =1,183)
smokers who completed an online survey. To identify a unidimensional set of
items, we conducted item factor analyses, item response theory analyses, and
differential item functioning analyses. Additionally, we evaluated the
performance of fixed-item short forms (SFs) and computer adaptive tests (CATs) to
efficiently assess the construct. RESULTS: Eighteen items were included in the
item banks (15 common across daily and nondaily smokers, 1 unique to daily, 2
unique to nondaily). The item banks are strongly unidimensional, highly reliable
(reliability = 0.95 for both), and perform similarly across gender, age, and
race/ethnicity groups. A SF common to daily and nondaily smokers consists of 6
items (reliability = 0.86). Results from simulated CATs indicated that, on
average, less than 8 items are needed to assess the construct with adequate
precision using the item banks. CONCLUSIONS: These analyses identified a new set
of items that can assess the positive emotional and sensory expectancies of
smoking in a reliable and standardized manner. Considerable efficiency in
assessing this construct can be achieved by using the item bank SF, employing
computer adaptive tests, or selecting subsets of items tailored to specific
research or clinical purposes.
PMID- 25118229
TI - Development of the PROMIS health expectancies of smoking item banks.
AB - INTRODUCTION: Smokers' health-related outcome expectancies are associated with a
number of important constructs in smoking research, yet there are no measures
currently available that focus exclusively on this domain. This paper describes
the development and evaluation of item banks for assessing the health
expectancies of smoking. METHODS: Using data from a sample of daily (N = 4,201)
and nondaily (N = 1,183) smokers, we conducted a series of item factor analyses,
item response theory analyses, and differential item functioning analyses
(according to gender, age, and race/ethnicity) to arrive at a unidimensional set
of health expectancies items for daily and nondaily smokers. We also evaluated
the performance of short forms (SFs) and computer adaptive tests (CATs) to
efficiently assess health expectancies. RESULTS: A total of 24 items were
included in the Health Expectancies item banks; 13 items are common across daily
and nondaily smokers, 6 are unique to daily, and 5 are unique to nondaily. For
both daily and nondaily smokers, the Health Expectancies item banks are
unidimensional, reliable (reliability = 0.95 and 0.96, respectively), and perform
similarly across gender, age, and race/ethnicity groups. A SF common to daily and
nondaily smokers consists of 6 items (reliability = 0.87). Results from simulated
CATs showed that health expectancies can be assessed with good precision with an
average of 5-6 items adaptively selected from the item banks. CONCLUSIONS: Health
expectancies of smoking can be assessed on the basis of these item banks via SFs,
CATs, or through a tailored set of items selected for a specific research
purpose.
PMID- 25118230
TI - Development of the PROMIS negative psychosocial expectancies of smoking item
banks.
AB - INTRODUCTION: Negative psychosocial expectancies of smoking include aspects of
social disapproval and disappointment in oneself. This paper describes analyses
conducted to develop and evaluate item banks for assessing psychosocial
expectancies among daily and nondaily smokers. METHODS: Using data from a sample
of daily (N = 4,201) and nondaily (N =1,183) smokers, we conducted a series of
item factor analyses, item response theory analyses, and differential item
functioning analyses (according to gender, age, and race/ethnicity) to arrive at
a unidimensional set of psychosocial expectancies items for daily and nondaily
smokers. We also evaluated performance of short forms (SFs) and computer adaptive
tests (CATs) to efficiently assess psychosocial expectancies. RESULTS: A total of
21 items were included in the Psychosocial Expectancies item banks: 14 items are
common across daily and nondaily smokers, 6 are unique to daily, and 1 is unique
to nondaily. For both daily and nondaily smokers, the Psychosocial Expectancies
item banks are strongly unidimensional, highly reliable (reliability = 0.95 and
0.93, respectively), and perform similarly across gender, age, and race/ethnicity
groups. A SF common to daily and nondaily smokers consists of 6 items
(reliability = 0.85). Results from simulated CATs showed that, on average, fewer
than 8 items are needed to assess psychosocial expectancies with adequate
precision when using the item banks. CONCLUSIONS: Psychosocial expectancies of
smoking can be assessed on the basis of these item banks via the SF, by using
CAT, or through a tailored set of items selected for a specific research purpose.
PMID- 25118233
TI - Delivering on its promises: the PROMIS Smoking Initiative item banks.
PMID- 25118231
TI - Development of the PROMIS Social Motivations for Smoking item banks.
AB - INTRODUCTION: Smoking behavior is influenced by social motivations such as the
expected social benefits of smoking and the social cues that induce craving. This
paper describes development of the PROMIS Social Motivations for Smoking item
banks, which will serve to standardize assessment of these social motivations
among daily and nondaily smokers. METHODS: Daily (N = 4,201) and nondaily (N
=1,183) smokers completed an online survey. Item factor analyses, item response
theory analyses, and differential item functioning analyses were conducted to
identify a unidimensional set of items for each group. Short forms (SFs) and
computer adaptive tests (CATs) were evaluated as tools for more efficiently
assessing this construct. RESULTS: A total of 15 items were included in the item
banks (9 items common to daily and nondaily smokers, 3 unique to daily, 3 unique
to nondaily). Scores based on full item banks are highly reliable (reliability =
0.90-0.91). Additionally, the item banks are strongly unidimensional and perform
similarly across gender, age, and race/ethnicity groups. A fixed SF for use with
both daily and nondaily smokers consists of 4 items (reliability = 0.80). Results
from simulated CATs showed that, on average, fewer than 5 items are needed to
assess this construct with adequate precision using the item banks. CONCLUSIONS:
A new set of items has been identified for assessing the social motivations for
smoking in a reliable, standardized manner for daily and nondaily smokers. In
addition to using the full item banks, efficient assessment can be achieved by
using SFs, employing CATs, or selecting items tailored to specific research or
clinical purposes.
PMID- 25118232
TI - The PROMIS Smoking Initiative: initial validity evidence for six new smoking item
banks.
AB - INTRODUCTION: The Patient-Reported Outcomes Measurement Information System
(PROMIS) Smoking Initiative has developed 6 item banks for assessing smoking
behaviors and biopsychosocial correlates of smoking among daily and nondaily
adult cigarette smokers. This paper presents descriptive information and
preliminary validity evidence for the item banks (Nicotine Dependence, Coping
Expectancies, Emotional and Sensory Expectancies, Health Expectancies,
Psychosocial Expectancies, and Social Motivations). METHODS: Using data from a
large sample of daily (N = 4,201) and nondaily (N = 1,183) smokers, we generated
mean daily and nondaily smoking bank scores according to select demographic
groups. We also examined correlations among the 6 banks and examined the
associations of bank scores with smoking behavior items (e.g., quantity of
smoking, interest in quitting) and select health-related quality of life measures
(i.e., physical functioning, anxiety, alcohol consumption). RESULTS: Correlations
among the 6 banks are moderate (daily mean r = .48, range = .04-.80; nondaily
mean r = .47, range = .12-.75). The pattern of associations between bank scores
and other measures provides validity evidence for the bank domains (e.g.,
nicotine dependence is most strongly associated with smoking quantity and time to
first cigarette of the day; health and psychosocial expectancies are most related
to quitting recency and interest; coping expectancies are strongly associated
with anxiety). CONCLUSIONS: These analyses provide useful descriptive information
about the 6 smoking item banks as well as preliminary evidence for their
validity. Independent sample data are currently being collected to replicate
these findings, to establish test-retest reliability, and to develop crosswalks
to existing smoking measures (e.g., nicotine dependence to Fagerstrom Test for
Nicotine Dependence). Future research will also evaluate the bank scores'
sensitivity to change.
PMID- 25118234
TI - Essentiality of succinate dehydrogenase in Mycobacterium smegmatis and its role
in the generation of the membrane potential under hypoxia.
AB - Succinate:quinone oxidoreductase (Sdh) is a membrane-bound complex that couples
the oxidation of succinate to fumarate in the cytoplasm to the reduction of
quinone to quinol in the membrane. Mycobacterial species harbor genes for two
putative sdh operons, but the individual roles of these two operons are unknown.
In this communication, we show that Mycobacterium smegmatis mc(2)155 expresses
two succinate dehydrogenases designated Sdh1 and Sdh2. Sdh1 is encoded by a five
gene operon (MSMEG_0416-MSMEG_0420), and Sdh2 is encoded by a four-gene operon
(MSMEG_1672-MSMEG_1669). These two operons are differentially expressed in
response to carbon limitation, hypoxia, and fumarate, as monitored by sdh
promoter-lacZ fusions. While deletion of the sdh1 operon did not yield any growth
phenotypes on succinate or other nonfermentable carbon sources, the sdh2 operon
could be deleted only in a merodiploid background, demonstrating that Sdh2 is
essential for growth. Sdh activity and succinate-dependent proton pumping were
detected in cells grown aerobically, as well as under hypoxia. Fumarate reductase
activity was absent under these conditions, indicating that neither Sdh1 nor Sdh2
could catalyze the reverse reaction. Sdh activity was inhibited by the Sdh
inhibitor 3-nitroproprionate (3NP), and treatment with 3NP dissipated the
membrane potential of wild-type or Deltasdh1 mutant cells under hypoxia but not
that of cells grown aerobically. These data imply that Sdh2 is the generator of
the membrane potential under hypoxia, an essential role for the cell. IMPORTANCE:
Complex II or succinate dehydrogenase (Sdh) is a major respiratory enzyme that
couples the oxidation of succinate to fumarate in the cytoplasm to the reduction
of quinone to quinol in the membrane. Mycobacterial species harbor genes for two
putative sdh operons, sdh1 and sdh2, but the individual roles of these two
operons are unknown. In this communication, we show that sdh1 and sdh2 are
differentially expressed in response to energy limitation, oxygen tension, and
alternative electron acceptor availability, suggesting distinct functional
cellular roles. Sdh2 was essential for growth and generation of the membrane
potential in hypoxic cells. Given the essentiality of succinate dehydrogenase and
oxidative phosphorylation in the growth cycle of Mycobacterium tuberculosis, the
potential exists to develop new antituberculosis agents against the mycobacterial
succinate dehydrogenase. This enzyme has been proposed as a potential target for
the development of new chemotherapeutic agents against intracellular parasites
and mitochondrion-associated disease.
PMID- 25118235
TI - A new method to determine in vivo interactomes reveals binding of the Legionella
pneumophila effector PieE to multiple rab GTPases.
AB - Legionella pneumophila, the causative agent of Legionnaires' disease, uses the
Dot/Icm type IV secretion system (T4SS) to translocate more than 300 effectors
into host cells, where they subvert host cell signaling. The function and host
cell targets of most effectors remain unknown. PieE is a 69-kDa Dot/Icm effector
containing three coiled-coil (CC) regions and 2 transmembrane (TM) helices
followed by a fourth CC region. Here, we report that PieE dimerized by an
interaction between CC3 and CC4. We found that ectopically expressed PieE
localized to the endoplasmic reticulum (ER) and induced the formation of
organized smooth ER, while following infection PieE localized to the Legionella
containing vacuole (LCV). To identify the physiological targets of PieE during
infection, we established a new purification method for which we created an A549
cell line stably expressing the Escherichia coli biotin ligase BirA and infected
the cells with L. pneumophila expressing PieE fused to a BirA-specific
biotinylation site and a hexahistidine tag. Following tandem Ni(2+)
nitrilotriacetic acid (NTA) and streptavidin affinity chromatography, the
effector-target complexes were analyzed by mass spectrometry. This revealed
interactions of PieE with multiple host cell proteins, including the Rab GTPases
1a, 1b, 2a, 5c, 6a, 7, and 10. Binding of the Rab GTPases, which was validated by
yeast two-hybrid binding assays, was mediated by the PieE CC1 and CC2. In
summary, using a novel, highly specific strategy to purify effector complexes
from infected cells, which is widely applicable to other pathogens, we identified
PieE as a multidomain LCV protein with promiscuous Rab GTPase-binding capacity.
IMPORTANCE: The respiratory pathogen Legionella pneumophila uses the Dot/Icm type
IV secretion system to translocate more than 300 effector proteins into host
cells. The function of most effectors in infection remains unknown. One of the
bottlenecks for their characterization is the identification of target proteins.
Frequently used in vitro approaches are not applicable to all effectors and
suffer from high rates of false positives or missed interactions, as they are not
performed in the context of an infection. Here, we determine key functional
domains of the effector PieE and describe a new method to identify host cell
targets under physiological infection conditions. Our approach, which is
applicable to other pathogens, uncovered the interaction of PieE with several
proteins involved in membrane trafficking, in particular Rab GTPases, revealing
new details of the Legionella infection strategy and demonstrating the potential
of this method to greatly advance our understanding of the molecular basis of
infection.
PMID- 25118236
TI - Whole-animal chemical screen identifies colistin as a new immunomodulator that
targets conserved pathways.
AB - The purpose of this study was to take advantage of the nematode Caenorhabditis
elegans to perform a whole-animal chemical screen to identify potential immune
activators that may confer protection against bacterial infections. We identified
45 marketed drugs, out of 1,120 studied compounds, that are capable of activating
a conserved p38/PMK-1 mitogen-activated protein kinase pathway required for
innate immunity. One of these drugs, the last-resort antibiotic colistin,
protected against infections by the Gram-negative pathogens Yersinia pestis and
Pseudomonas aeruginosa but not by the Gram-positive pathogens Enterococcus
faecalis and Staphylococcus aureus. Protection was independent of the
antibacterial activity of colistin, since the drug was administered
prophylactically prior to the infections and it was also effective against
antibiotic-resistant bacteria. Immune activation by colistin is mediated not only
by the p38/PMK-1 pathway but also by the conserved FOXO transcription factor DAF
16 and the transcription factor SKN-1. Furthermore, p38/PMK-1 was found to be
required in the intestine for immune activation by colistin. Enhanced p38/PMK-1
mediated immune responses by colistin did not reduce the bacterial burden,
indicating that the pathway plays a role in the development of host tolerance to
infections by Gram-negative bacteria. IMPORTANCE: The innate immune system
represents the front line of our defenses against invading microorganisms. Given
the ever-increasing resistance to antibiotics developed by bacterial pathogens,
the possibility of boosting immune defenses represents an interesting,
complementary approach to conventional antibiotic treatments. Here we report that
the antibiotic colistin can protect against infections by a mechanism that is
independent of its microbicidal activity. Prophylactic treatment with colistin
activates a conserved p38/PMK-1 pathway in the intestine that helps the host
better tolerate a bacterial infection. Since p38/PMK-1-mediated immune responses
appear to be conserved from plants to mammals, colistin may also activate
immunity in higher organisms, including humans. Antibiotics with immunomodulatory
properties have the potential of improving the long-term outcome of patients with
chronic infectious diseases.
PMID- 25118237
TI - Influenza virus A/Anhui/1/2013 (H7N9) replicates efficiently in the upper and
lower respiratory tracts of cynomolgus macaques.
AB - In March 2013, three fatal human cases of infection with influenza A virus (H7N9)
were reported in China. Since then, human cases have been accumulating. Given the
public health importance of this virus, we performed a pathogenicity study of the
H7N9 virus in the cynomolgus macaque model, focusing on clinical aspects of
disease, radiographic, histological, and gene expression profile changes in the
upper and lower respiratory tracts, and changes in systemic cytokine and
chemokine profiles during infection. Cynomolgus macaques developed transient,
mild to severe disease with radiographic evidence of pulmonary infiltration.
Virus replicated in the upper as well as lower respiratory tract, with sustained
replication in the upper respiratory tract until the end of the experiment at 6
days after inoculation. Virus shedding occurred mainly via the throat.
Histopathological changes in the lungs were similar to those observed in humans,
albeit less severe, with diffuse alveolar damage, infiltration of
polymorphonuclear cells, formation of hyaline membranes, pneumocyte hyperplasia,
and fibroproliferative changes. Analysis of gene expression profiles in lung
lesions identified pathways involved in tissue damage during H7N9 infection as
well as leads for development of therapeutics targeting host responses rather
than virus replication. Overall, H7N9 infection was not as severe in cynomolgus
macaques as in humans, supporting the possible role of underlying medical
complications in disease severity as discussed for human H7N9 infection (H. N.
Gao et al., N. Engl. J. Med. 368:2277-2285, 2013, doi:10.1056/NEJMoa1305584).
IMPORTANCE: Influenza A virus H7N9 emerged early in 2013, and human cases have
continued to emerge since then. Although H7N9 virus-induced disease in humans is
often very severe and even lethal, the majority of reported H7N9 cases occurred
in older people and people with underlying medical conditions. To better
understand the pathogenicity of this virus, healthy cynomolgus macaques were
inoculated with influenza A virus H7N9. Cynomolgus macaques were used as a model
because the receptor distribution for H7N9 virus in macaques was recently shown
to be more similar to that in humans than that of other frequently used animal
models. From comparison with previous studies, we conclude that the emerging H7N9
influenza virus was more pathogenic in cynomolgus macaques than seasonal
influenza A viruses and most isolates of the pandemic H1N1 virus but less
pathogenic than the 1918 Spanish influenza virus or highly pathogenic avian
influenza (HPAI) H5N1 virus.
PMID- 25118238
TI - Differential modulation by Akkermansia muciniphila and Faecalibacterium
prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse
gut organoids.
AB - The gut microbiota is essential for numerous aspects of human health. However,
the underlying mechanisms of many host-microbiota interactions remain unclear.
The aim of this study was to characterize effects of the microbiota on host
epithelium using a novel ex vivo model based on mouse ileal organoids. We have
explored the transcriptional response of organoids upon exposure to short-chain
fatty acids (SCFAs) and products generated by two abundant microbiota
constituents, Akkermansia muciniphila and Faecalibacterium prausnitzii. We
observed that A. muciniphila metabolites affect various transcription factors and
genes involved in cellular lipid metabolism and growth, supporting previous in
vivo findings. Contrastingly, F. prausnitzii products exerted only weak effects
on host transcription. Additionally, A. muciniphila and its metabolite propionate
modulated expression of Fiaf, Gpr43, histone deacetylases (HDACs), and peroxisome
proliferator-activated receptor gamma (Ppargamma), important regulators of
transcription factor regulation, cell cycle control, lipolysis, and satiety. This
work illustrates that specific bacteria and their metabolites differentially
modulate epithelial transcription in mouse organoids. We demonstrate that
intestinal organoids provide a novel and powerful ex vivo model for host
microbiome interaction studies. IMPORTANCE: We investigated the influence of the
gut microbiota and microbially produced short-chain fatty acids (SCFAs) on gut
functioning. Many commensal bacteria in the gut produce SCFAs, particularly
butyrate, acetate, and propionate, which have been demonstrated to reduce the
risk of gastrointestinal disorders. Organoids-small crypt-villus structures grown
from ileal intestinal stem cells-were exposed to SCFAs and two specific gut
bacteria. Akkermansia muciniphila, found in the intestinal mucus, was recently
shown to have a favorable effect on the disrupted metabolism associated with
obesity. Faecalibacterium prausnitzii is a commensal gut bacterium, the absence
of which may be associated with Crohn's disease. We showed that in our model, A.
muciniphila induces stronger effects on the host than F. prausnitzii. We observed
that A. muciniphila and propionate affect the expression of genes involved in
host lipid metabolism and epigenetic activation or silencing of gene expression.
We demonstrated that organoids provide a powerful tool for host-microbe
interaction studies.
PMID- 25118239
TI - Glycan degradation (GlyDeR) analysis predicts mammalian gut microbiota abundance
and host diet-specific adaptations.
AB - Glycans form the primary nutritional source for microbes in the human gut, and
understanding their metabolism is a critical yet understudied aspect of
microbiome research. Here, we present a novel computational pipeline for modeling
glycan degradation (GlyDeR) which predicts the glycan degradation potency of
10,000 reference glycans based on either genomic or metagenomic data. We first
validated GlyDeR by comparing degradation profiles for genomes in the Human
Microbiome Project against KEGG reaction annotations. Next, we applied GlyDeR to
the analysis of human and mammalian gut microbial communities, which revealed
that the glycan degradation potential of a community is strongly linked to host
diet and can be used to predict diet with higher accuracy than sequence data
alone. Finally, we show that a microbe's glycan degradation potential is
significantly correlated (R = 0.46) with its abundance, with even higher
correlations for potential pathogens such as the class Clostridia (R = 0.76).
GlyDeR therefore represents an important tool for advancing our understanding of
bacterial metabolism in the gut and for the future development of more effective
prebiotics for microbial community manipulation. IMPORTANCE: The increased
availability of high-throughput sequencing data has positioned the gut microbiota
as a major new focal point for biomedical research. However, despite the
expenditure of huge efforts and resources, sequencing-based analysis of the
microbiome has uncovered mostly associative relationships between human health
and diet, rather than a causal, mechanistic one. In order to utilize the full
potential of systems biology approaches, one must first characterize the
metabolic requirements of gut bacteria, specifically, the degradation of glycans,
which are their primary nutritional source. We developed a computational
framework called GlyDeR for integrating expert knowledge along with high
throughput data to uncover important new relationships within glycan metabolism.
GlyDeR analyzes particular bacterial (meta)genomes and predicts the potency by
which they degrade a variety of different glycans. Based on GlyDeR, we found a
clear connection between microbial glycan degradation and human diet, and we
suggest a method for the rational design of novel prebiotics.
PMID- 25118240
TI - Phyllosphere microbiota composition and microbial community transplantation on
lettuce plants grown indoors.
AB - The aerial surfaces of plants, or phyllosphere, are microbial habitats important
to plant and human health. In order to accurately investigate microbial
interactions in the phyllosphere under laboratory conditions, the composition of
the phyllosphere microbiota should be representative of the diversity of
microorganisms residing on plants in nature. We found that Romaine lettuce grown
in the laboratory contained 10- to 100-fold lower numbers of bacteria than age
matched, field-grown lettuce. The bacterial diversity on laboratory-grown plants
was also significantly lower and contained relatively higher proportions of
Betaproteobacteria as opposed to the Gammaproteobacteria-enriched communities on
field lettuce. Incubation of field-grown Romaine lettuce plants in environmental
growth chambers for 2 weeks resulted in bacterial cell densities and taxa similar
to those on plants in the field but with less diverse bacterial populations
overall. In comparison, the inoculation of laboratory-grown Romaine lettuce
plants with either freshly collected or cryopreserved microorganisms recovered
from field lettuce resulted in the development of a field-like microbiota on the
lettuce within 2 days of application. The survival of an inoculated strain of
Escherichia coli O157:H7 was unchanged by microbial community transfer; however,
the inoculation of E. coli O157:H7 onto those plants resulted in significant
shifts in the abundance of certain taxa. This finding was strictly dependent on
the presence of a field-associated as opposed to a laboratory-associated
microbiota on the plants. Phyllosphere microbiota transplantation in the
laboratory will be useful for elucidating microbial interactions on plants that
are important to agriculture and microbial food safety. IMPORTANCE: The
phyllosphere is a habitat for a variety of microorganisms, including bacteria
with significant relevance to plant and human health. Some indigenous epiphytic
bacteria might affect the persistence of human food-borne pathogens in the
phyllosphere. However, studies on human pathogens are typically performed on
plants grown indoors. This study compares the phyllosphere microbiota on Romaine
lettuce plants grown in a Salinas Valley, CA, field to that on lettuce plants
grown in environmental chambers. We show that phyllosphere microbiota from
laboratory-grown plants is distinct from that colonizing plants grown in the
field and that the field microbiota can be successfully transferred to plants
grown indoors. The microbiota transplantation method was used to examine
alterations to the phyllosphere microbiota after Escherichia coli O157:H7
inoculation on lettuce plants in a controlled environment. Our findings show the
importance and validity of phyllosphere microbiota transplantation for future
phyllosphere microbiology research.
PMID- 25118241
TI - Cross talk between the cell wall integrity and cyclic AMP/protein kinase A
pathways in Cryptococcus neoformans.
AB - Cryptococcus neoformans is a fungal pathogen of immunocompromised people that
causes fatal meningitis. The fungal cell wall is essential to viability and
pathogenesis of C. neoformans, and biosynthesis and repair of the wall is
primarily controlled by the cell wall integrity (CWI) signaling pathway. Previous
work has shown that deletion of genes encoding the four major kinases in the CWI
signaling pathway, namely, PKC1, BCK1, MKK2, and MPK1 results in severe cell wall
phenotypes, sensitivity to a variety of cell wall stressors, and for Mpk1,
reduced virulence in a mouse model. Here, we examined the global transcriptional
responses to gene deletions of BCK1, MKK2, and MPK1 compared to wild-type cells.
We found that over 1,000 genes were differentially expressed in one or more of
the deletion strains, with 115 genes differentially expressed in all three
strains, many of which have been identified as genes regulated by the cyclic AMP
(cAMP)/protein kinase A (PKA) pathway. Biochemical measurements of cAMP levels in
the kinase deletion strains revealed significantly less cAMP in all of the
deletion strains compared to the wild-type strain. The deletion strains also
produced significantly smaller capsules than the wild-type KN99 strain did under
capsule-inducing conditions, although the levels of capsule they shed were
similar to those shed by the wild type. Finally, addition of exogenous cAMP led
to reduced sensitivity to cell wall stress and restored surface capsule to levels
near those of wild type. Thus, we have direct evidence of cross talk between the
CWI and cAMP/PKA pathways that may have important implications for regulation of
cell wall and capsule homeostasis. IMPORTANCE: Cryptococcus neoformans is a
fungal pathogen of immunocompromised people that causes fatal meningitis. The
fungal cell wall is essential to viability and pathogenesis of C. neoformans, and
biosynthesis and repair of the wall are primarily controlled by the cell wall
integrity (CWI) signaling pathway. In this study, we demonstrate that deletion of
any of three core kinases in the CWI pathway impacts not only the cell wall but
also the amount of surface capsule. Deletion of any of the kinases results in
significantly reduced cellular cyclic AMP (cAMP) levels, and addition of
exogenous cAMP rescues the capsule defect and some cell wall defects, supporting
a direct role for the CWI pathway in regulation of capsule in conjunction with
the cAMP/protein kinase A pathway.
PMID- 25118243
TI - Fur is the master regulator of the extraintestinal pathogenic Escherichia coli
response to serum.
AB - Drug-resistant extraintestinal pathogenic Escherichia coli (ExPEC) strains are
the major cause of colisepticemia (colibacillosis), a condition that has become
an increasing public health problem in recent years. ExPEC strains are
characterized by high resistance to serum, which is otherwise highly toxic to
most bacteria. To understand how these bacteria survive and grow in serum, we
performed system-wide analyses of their response to serum, making a clear
distinction between the responses to nutritional immunity and innate immunity.
Thus, mild heat inactivation of serum destroys the immune complement and
abolishes the bactericidal effect of serum (inactive serum), making it possible
to examine nutritional immunity. We used a combination of deep RNA sequencing and
proteomics in order to characterize ExPEC genes whose expression is affected by
the nutritional stress of serum and by the immune complement. The major change in
gene expression induced by serum-active and inactive-involved metabolic genes. In
particular, the serum metabolic response is coordinated by three transcriptional
regulators, Fur, BasR, and CysB. Fur alone was responsible for more than 80% of
the serum-induced transcriptional response. Consistent with its role as a major
serum response regulator, deletion of Fur renders the bacteria completely serum
sensitive. These results highlight the role of metabolic adaptation in
colisepticemia and virulence. IMPORTANCE: Drug-resistant extraintestinal
pathogenic Escherichia coli (ExPEC) strains have emerged as major pathogens,
especially in community- and hospital-acquired infections. These bacteria cause a
large spectrum of syndromes, the most serious of which is septicemia, a condition
with a high mortality rate. These bacterial strains are characterized by high
resistance to serum, otherwise highly toxic to most bacteria. To understand the
basis of this resistance, we carried out system-wide analyses of the response of
ExPEC strains to serum by using proteomics and deep RNA sequencing. The major
changes in gene expression induced by exposure to serum involved metabolic genes,
not necessarily implicated in relation to virulence. One metabolic regulator-Fur
involved in iron metabolism was responsible for more than 80% of the serum
induced response, and its deletion renders the bacteria completely serum
sensitive. These results highlight the role of metabolic adaptation in virulence.
PMID- 25118244
TI - Pollen-specific activation of Arabidopsis retrogenes is associated with global
transcriptional reprogramming.
AB - Duplications allow for gene functional diversification and accelerate genome
evolution. Occasionally, the transposon amplification machinery reverse
transcribes the mRNA of a gene, integrates it into the genome, and forms an RNA
duplicated copy: the retrogene. Although retrogenes have been found in plants,
their biology and evolution are poorly understood. Here, we identified 251 (216
novel) retrogenes in Arabidopsis thaliana, corresponding to 1% of protein-coding
genes. Arabidopsis retrogenes are derived from ubiquitously transcribed parents
and reside in gene-rich chromosomal regions. Approximately 25% of retrogenes are
cotranscribed with their parents and 3% with head-to-head oriented neighbors.
This suggests transcription by novel promoters for 72% of Arabidopsis retrogenes.
Many retrogenes reach their transcription maximum in pollen, the tissue analogous
to animal spermatocytes, where upregulation of retrogenes has been found
previously. This implies an evolutionarily conserved mechanism leading to this
transcription pattern of RNA-duplicated genes. During transcriptional repression,
retrogenes are depleted of permissive chromatin marks without an obvious
enrichment for repressive modifications. However, this pattern is common to many
other pollen-transcribed genes independent of their evolutionary origin. Hence,
retroposition plays a role in plant genome evolution, and the developmental
transcription pattern of retrogenes suggests an analogous regulation of RNA
duplicated genes in plants and animals.
PMID- 25118245
TI - Dynamics of vacuoles and H+-pyrophosphatase visualized by monomeric green
fluorescent protein in Arabidopsis: artifactual bulbs and native intravacuolar
spherical structures.
AB - We prepared Arabidopsis thaliana lines expressing a functional green fluorescent
protein (GFP)-linked vacuolar H(+)-pyrophosphatase (H(+)-PPase) under the control
of its own promoter to investigate morphological dynamics of vacuoles and tissue
specific expression of H(+)-PPase. The lines obtained had spherical structures in
vacuoles with strong fluorescence, which are referred to as bulbs. Quantitative
analyses revealed that the occurrence of the bulbs correlated with the amount of
GFP. Next, we prepared a construct of H(+)-PPase linked with a nondimerizing GFP
(mGFP); we detected no bulbs. These results indicate that the membranes adhere
face-to-face by antiparallel dimerization of GFP, resulting in the formation of
bulbs. In plants expressing H(+)-PPase-mGFP, intravacuolar spherical structures
with double membranes, which differed from bulbs in fluorescence intensity and
intermembrane spacing, were still observed in peripheral endosperm, pistil
epidermis and hypocotyls. Four-dimensional imaging revealed the dynamics of
formation, transformation, and disappearance of intravacuolar spherical
structures and transvacuolar strands in living cells. Visualization of H(+)-PPase
mGFP revealed intensive accumulation of the enzyme, not only in dividing and
elongating cells but also in mesophyll, phloem, and nectary cells, which may have
high sugar content. Dynamic morphological changes including transformation of
vacuolar structures between transvacuolar strands, intravacuolar sheet-like
structures, and intravacuolar spherical structures were also revealed.
PMID- 25118248
TI - Advance consent, critical interests and dementia research.
AB - Although advance directives have become a familiar instrument within the context
of treatment, there has been minimal support for their expansion into the context
of research. In this paper I argue that the principle of precedent autonomy that
grants a competent person the right to refuse life-sustaining treatment when
later incompetent, also grants a competent person the right to consent to
research that is greater than minimal risk. An examination of the principle of
precedent autonomy reveals that a future-binding research decision is within the
scope of a competent person's critical interests, if the decision is consistent
with what the person believes gives her life intrinsic value.
PMID- 25118247
TI - Oligosaccharyltransferase subunits bind polypeptide substrate to locally enhance
N-glycosylation.
AB - Oligosaccharyltransferase is a multiprotein complex that catalyzes asparagine
linked glycosylation of diverse proteins. Using yeast genetics and
glycoproteomics, we found that transient interactions between nascent polypeptide
and Ost3p/Ost6p, homologous subunits of oligosaccharyltransferase, were able to
modulate glycosylation efficiency in a site-specific manner in vivo. These
interactions were driven by hydrophobic and electrostatic complementarity between
amino acids in the peptide-binding groove of Ost3p/Ost6p and the sequestered
stretch of substrate polypeptide. Based on this dependence, we used in vivo
scanning mutagenesis and in vitro biochemistry to map the precise interactions
that affect site-specific glycosylation efficiency. We conclude that transient
binding of substrate polypeptide by Ost3p/Ost6p increases glycosylation
efficiency at asparagines proximal and C-terminal to sequestered sequences. We
detail a novel mode of interaction between translocating nascent polypeptide and
oligosaccharyltransferase in which binding to Ost3p/Ost6p segregates a short
flexible loop of glycosylation-competent polypeptide substrate that is delivered
to the oligosaccharyltransferase active site for efficient modification.
PMID- 25118249
TI - Putative PmrA and PmcA are important for normal growth, morphogenesis and cell
wall integrity, but not for viability in Aspergillus nidulans.
AB - P-type Ca(2+)-transporting ATPases are Ca(2+) pumps, extruding cytosolic Ca(2+)
to the extracellular environment or the intracellular Ca(2+) store lumens. In
budding yeast, Pmr1 (plasma membrane ATPase related), and Pmc1 (plasma membrane
calcium-ATPase) cannot be deleted simultaneously for it to survive in standard
medium. Here, we deleted two putative Ca(2+) pumps, designated AnPmrA and AnPmcA,
from Aspergillus nidulans, and obtained the mutants DeltaanpmrA and DeltaanpmcA,
respectively. Then, using DeltaanpmrA as the starting strain, the promoter of its
anpmcA was replaced with the alcA promoter to secure the mutant
DeltaanpmrAalcApmcA or its anpmcA was deleted completely to produce the mutant
DeltaanpmrADeltapmcA. Different from the case in Saccharomyces cerevisiae, double
deletion of anpmrA and anpmcA was not lethal in A. nidulans. In addition,
deletion of anpmrA and/or anpmcA had produced growth defects, although
overexpression of AnPmc1 in DeltaanpmrAalcApmcA could not restore the growth
defects that resulted from the loss of AnPmrA. Moreover, we found AnPmrA was
indispensable for maintenance of normal morphogenesis, especially in low
Ca(2+)/Mn(2+) environments. Thus, our findings suggest AnPmrA and AnPmcA might
play important roles in growth, morphogenesis and cell wall integrity in A.
nidulans in a different way from that in yeasts.
PMID- 25118246
TI - Proteome-wide light/dark modulation of thiol oxidation in cyanobacteria revealed
by quantitative site-specific redox proteomics.
AB - Reversible protein thiol oxidation is an essential regulatory mechanism of
photosynthesis, metabolism, and gene expression in photosynthetic organisms.
Herein, we present proteome-wide quantitative and site-specific profiling of in
vivo thiol oxidation modulated by light/dark in the cyanobacterium Synechocystis
sp. PCC 6803, an oxygenic photosynthetic prokaryote, using a resin-assisted thiol
enrichment approach. Our proteomic approach integrates resin-assisted enrichment
with isobaric tandem mass tag labeling to enable site-specific and quantitative
measurements of reversibly oxidized thiols. The redox dynamics of ~2,100 Cys
sites from 1,060 proteins under light, dark, and 3-(3,4-dichlorophenyl)-1,1
dimethylurea (a photosystem II inhibitor) conditions were quantified. In addition
to relative quantification, the stoichiometry or percentage of oxidation
(reversibly oxidized/total thiols) for ~1,350 Cys-sites was also quantified. The
overall results revealed broad changes in thiol oxidation in many key biological
processes, including photosynthetic electron transport, carbon fixation, and
glycolysis. Moreover, the redox sensitivity along with the stoichiometric data
enabled prediction of potential functional Cys-sites for proteins of interest.
The functional significance of redox-sensitive Cys-sites in NADP-dependent
glyceraldehyde-3-phosphate dehydrogenase, peroxiredoxin (AhpC/TSA family protein
Sll1621), and glucose 6-phosphate dehydrogenase was further confirmed with site
specific mutagenesis and biochemical studies. Together, our findings provide
significant insights into the broad redox regulation of photosynthetic organisms.
PMID- 25118250
TI - Anionic lipids and the cytoskeletal proteins MreB and RodZ define the spatio
temporal distribution and function of membrane stress controller PspA in
Escherichia coli.
AB - All cell types must maintain the integrity of their membranes. The conserved
bacterial membrane-associated protein PspA is a major effector acting upon
extracytoplasmic stress and is implicated in protection of the inner membrane of
pathogens, formation of biofilms and multi-drug-resistant persister cells. PspA
and its homologues in Gram-positive bacteria and archaea protect the cell
envelope whilst also supporting thylakoid biogenesis in cyanobacteria and higher
plants. In enterobacteria, PspA is a dual function protein negatively regulating
the Psp system in the absence of stress and acting as an effector of membrane
integrity upon stress. We show that in Escherichia coli the low-order oligomeric
PspA regulatory complex associates with cardiolipin-rich, curved polar inner
membrane regions. There, cardiolipin and the flotillin 1 homologue YqiK support
the PspBC sensors in transducing a membrane stress signal to the PspA-PspF
inhibitory complex. After stress perception, PspA high-order oligomeric effector
complexes initially assemble in polar membrane regions. Subsequently, the
discrete spatial distribution and dynamics of PspA effector(s) in lateral
membrane regions depend on the actin homologue MreB and the peptidoglycan
machinery protein RodZ. The consequences of loss of cytoplasmic membrane anionic
lipids, MreB, RodZ and/or YqiK suggest that the mode of action of the PspA
effector is closely associated with cell envelope organization.
PMID- 25118251
TI - Monophasic expression of FliC by Salmonella 4,[5],12:i:- DT193 does not alter its
pathogenicity during infection of porcine intestinal epithelial cells.
AB - Non-typhoidal serotypes of Salmonella enterica remain important food-borne
pathogens worldwide and the frequent emergence of epidemic strains in food
producing animals is a risk to public health. In recent years, Salmonella
4,[5],12:i:- isolates, expressing only phase 1 (FliC) of the two flagellar
antigens, have emerged and increased in prevalence worldwide. In Europe, the
majority of 4,[5],12:i:- isolates belong to phage types DT193 and DT120 of
Salmonella Typhimurium and pigs have been identified as the reservoir species. In
this study we investigated the ability of pig-derived monophasic (4,[5],12:i:-)
and biphasic DT193 isolates to invade a porcine intestinal epithelial cell line
(IPEC-1) and activate TLR-5, IL-8 and caspases. We found that the 4,[5],12:i:-
isolates exhibited comparable adhesion and invasion to that of the virulent S.
Typhimurium isolate 4/74, suggesting that these strains could be capable of
colonizing the small intestine of pigs in vivo. Infection with 4,[5],12:i:- and
biphasic DT193 isolates resulted in approximately the same level of TLR-5 (a
flagellin receptor) and IL-8 (a proinflammatory chemokine) mRNA upregulation. The
monophasic variants also elicited similar levels of caspase activation and
cytotoxicity to the phase-variable DT193 isolates. These findings suggest that
failure of 4,[5],12:i:- DT193 isolates to express a second phase of flagellar
antigen (FljB) is unlikely to hamper their pathogenicity during colonization of
the porcine intestinal tract.
PMID- 25118252
TI - Evolution of a genome-encoded bias in amino acid biosynthetic pathways is a
potential indicator of amino acid dynamics in the environment.
AB - Overcoming the stress of starvation is one of an organism's most challenging
phenotypic responses. Those organisms that frequently survive the challenge, by
virtue of their fitness, will have evolved genomes that are shaped by their
specific environments. Understanding this genotype-environment-phenotype
relationship at a deep level will require quantitative predictive models of the
complex molecular systems that link these aspects of an organism's existence.
Here, we treat one of the most fundamental molecular systems, protein synthesis,
and the amino acid biosynthetic pathways involved in the stringent response to
starvation. These systems face an inherent logical dilemma: Building an amino
acid biosynthetic pathway to synthesize its product-the cognate amino acid of the
pathway-may require that very amino acid when it is no longer available. To study
this potential "catch-22," we have created a generic model of amino acid
biosynthesis in response to sudden starvation. Our mathematical analysis and
computational results indicate that there are two distinctly different outcomes:
Partial recovery to a new steady state, or full system failure. Moreover, the
cell's fate is dictated by the cognate bias, the number of cognate amino acids in
the corresponding biosynthetic pathway relative to the average number of that
amino acid in the proteome. We test these implications by analyzing the proteomes
of over 1,800 sequenced microbes, which reveals statistically significant
evidence of low cognate bias, a genetic trait that would avoid the biosynthetic
quandary. Furthermore, these results suggest that the pattern of cognate bias,
which is readily derived by genome sequencing, may provide evolutionary clues to
an organism's natural environment.
PMID- 25118254
TI - Root-secreted nicotianamine from Arabidopsis halleri facilitates zinc
hypertolerance by regulating zinc bioavailability.
AB - Hyperaccumulators tolerate and accumulate extraordinarily high concentrations of
heavy metals. Content of the metal chelator nicotianamine (NA) in the root of
zinc hyperaccumulator Arabidopsis halleri is elevated compared with
nonhyperaccumulators, a trait that is considered to be one of the markers of a
hyperaccumulator. Using metabolite-profiling analysis of root secretions, we
found that excess zinc treatment induced secretion of NA in A. halleri roots
compared with the nonhyperaccumulator Arabidopsis thaliana. Metal speciation
analysis further revealed that the secreted NA forms a stable complex with
Zn(II). Supplying NA to a nonhyperaccumulator species markedly increased plant
zinc tolerance by decreasing zinc uptake. Therefore, NA secretion from A. halleri
roots facilitates zinc hypertolerance through forming a Zn(II)-NA complex outside
the roots to achieve a coordinated zinc uptake rate into roots. Secretion of NA
was also found to be responsible for the maintenance of iron homeostasis under
excess zinc. Together our results reveal root-secretion mechanisms associated
with hypertolerance and hyperaccumulation.
PMID- 25118256
TI - Digital inventory of Arabidopsis transcripts revealed by 61 RNA sequencing
samples.
AB - Alternative splicing is an essential biological process to generate proteome
diversity and phenotypic complexity. Recent improvements in RNA sequencing
accuracy and computational algorithms have provided unprecedented opportunities
to examine the expression levels of Arabidopsis (Arabidopsis thaliana)
transcripts. In this article, we analyzed 61 RNA sequencing samples from 10
totally independent studies of Arabidopsis and calculated the transcript
expression levels in different tissues, treatments, developmental stages, and
varieties. These data provide a comprehensive profile of Arabidopsis transcripts
with single-base resolution. We quantified the expression levels of 40,745
transcripts annotated in The Arabidopsis Information Resource 10, comprising 73%
common transcripts, 15% rare transcripts, and 12% nondetectable transcripts. In
addition, we investigated diverse common transcripts in detail, including
ubiquitous transcripts, dominant/subordinate transcripts, and switch transcripts,
in terms of their expression and transcript ratio. Interestingly, alternative
splicing was the highly enriched function for the genes related to
dominant/subordinate transcripts and switch transcripts. In addition, motif
analysis revealed that TC motifs were enriched in dominant transcripts but not in
subordinate transcripts. These motifs were found to have a strong relationship
with transcription factor activity. Our results shed light on the complexity of
alternative splicing and the diversity of the contributing factors.
PMID- 25118259
TI - RESTORE: REcovery after Serious Trauma--Outcomes, Resource use and patient
Experiences study protocol.
AB - BACKGROUND: Traumatic injury is a leading contributor to the overall global
burden of disease. However, there is a worldwide shortage of population data to
inform understanding of non-fatal injury burden. An improved understanding of the
pattern of recovery following trauma is needed to better estimate the burden of
injury, guide provision of rehabilitation services and care to injured people,
and inform guidelines for the monitoring and evaluation of disability outcomes.
OBJECTIVE: To provide a comprehensive overview of patient outcomes and
experiences in the first 5 years after serious injury. DESIGN: This is a
population-based, nested prospective cohort study using quantitative data
methods, supplemented by a qualitative study of a seriously injured participant
sample. PARTICIPANTS: All 2547 paediatric and adult major trauma patients
captured by the Victorian State Trauma Registry with a date of injury from 1 July
2011 to 30 June 2012 who survived to hospital discharge and did not opt-off from
the registry. ANALYSIS: To analyse the quantitative data and identify factors
that predict poor or good outcome, whether there is change over time, differences
in rates of recovery and change between key participant subgroups, multilevel
mixed effects regression models will be fitted. To analyse the qualitative data,
thematic analysis will be used to identify important themes and the relationships
between themes. CONTRIBUTION TO THE FIELD: The results of this project have the
potential to inform clinical decisions and public health policy, which can reduce
the burden of non-fatal injury and improve the lives of people living with the
consequences of severe injury.
PMID- 25118260
TI - TAK1 inhibition accelerates cellular senescence of retinal pigment epithelial
cells.
AB - PURPOSE: Oxidative stress and cellular senescence are known to contribute to the
development of AMD; however, the mechanism is not fully understood. This study
investigated the role of TGF-beta-activated kinase 1 (TAK1) in the senescence of
RPE cells as a model for the development of dry AMD. METHODS: Cultured human RPE
cells were treated with the TAK1 inhibitor 5Z-7-oxozeaenol for 1 hour, and then
treated with 200 MUM hydrogen peroxide for 1 hour. Human RPE cells that were not
pretreated with TAK1 inhibitor for 1 hour served as controls. Senescence
associated beta-galactosidase (SA-beta-gal) activity was detected by
histochemistry, and p53 expression by immunoblotting. Cell-cycle and apoptosis
rate in RPE cells were determined by flow cytometry. RESULTS: The TAK1 expression
in human RPE cells was high and was altered on oxidative stress. Transforming
growth factor-beta-activated kinase 1 inhibition led to reduction in cell
proliferation, cell-cycle arrest at G0/G1, and increased SA-beta-gal expression,
all known to be features of cell senescence. Exposure of cells to oxidative
stress combined with inhibition of TAK1 activity decreased the expression of
apoptotic proteins, such as p53, and promoted cellular senescence. Aberrant TAK1
activity in RPE cells triggered their secretion of factors that induced
hypertrophy and fibrotic changes in neighboring cells. CONCLUSIONS: The in vitro
evidence indicated a role for TAK1 in the onset of senescence in RPE cells. The
data shown hereby demonstrated that TAK1 activity is essential for maintaining
normal function of RPE cells. Elucidation of its role in mechanisms underlying
RPE cellular senescence induction may potentiate development of powerful tools
for halting the development of dry AMD.
PMID- 25118253
TI - Biotic interactions in the rhizosphere: a diverse cooperative enterprise for
plant productivity.
AB - Microbes and plants have evolved biochemical mechanisms to communicate with each
other. The molecules responsible for such communication are secreted during
beneficial or harmful interactions. Hundreds of these molecules secreted into the
rhizosphere have been identified, and their functions are being studied in order
to understand the mechanisms of interaction and communication among the different
members of the rhizosphere community. The importance of root and microbe
secretion to the underground habitat in improving crop productivity is
increasingly recognized, with the discovery and characterization of new secreting
compounds found in the rhizosphere. Different omic approaches, such as genomics,
transcriptomics, proteomics, and metabolomics, have expanded our understanding of
the first signals between microbes and plants. In this review, we highlight the
more recent discoveries related to molecules secreted into the rhizosphere and
how they affect plant productivity, either negatively or positively. In addition,
we include a survey of novel approaches to studying the rhizosphere and emerging
opportunities to direct future studies.
PMID- 25118255
TI - Large-scale identification of gibberellin-related transcription factors defines
group VII ETHYLENE RESPONSE FACTORS as functional DELLA partners.
AB - DELLA proteins are the master negative regulators in gibberellin (GA) signaling
acting in the nucleus as transcriptional regulators. The current view of DELLA
action indicates that their activity relies on the physical interaction with
transcription factors (TFs). Therefore, the identification of TFs through which
DELLAs regulate GA responses is key to understanding these responses from a
mechanistic point of view. Here, we have determined the TF interactome of the
Arabidopsis (Arabidopsis thaliana) DELLA protein GIBBERELLIN INSENSITIVE and
screened a collection of conditional TF overexpressors in search of those that
alter GA sensitivity. As a result, we have found RELATED TO APETALA2.3, an
ethylene-induced TF belonging to the group VII ETHYLENE RESPONSE FACTOR of the
APETALA2/ethylene responsive element binding protein superfamily, as a DELLA
interactor with physiological relevance in the context of apical hook
development. The combination of transactivation assays and chromatin
immunoprecipitation indicates that the interaction with GIBBERELLIN INSENSITIVE
impairs the activity of RELATED TO APETALA2.3 on the target promoters. This
mechanism represents a unique node in the cross regulation between the GA and
ethylene signaling pathways controlling differential growth during apical hook
development.
PMID- 25118261
TI - Increased corneal epithelial permeability after overnight sleep.
AB - PURPOSE: To investigate factors of ethnicity, sex, age, and diurnal variation on
human corneal epithelial permeability. METHODS: Data of corneal epithelial
permeability to sodium fluorescein (Pdc) were collected from 374 noncontact lens
wearers at various times after awakening throughout the day. Mixed-effect models
were developed to investigate the association between Pdc and factors of
interest, including time awake (TA), age, sex, ethnicity, and interactions of
these factors. RESULTS: Two models evaluated the "Pdc recovery period" from
awakening to 2 hours (Model 1) and the "Pdc plateau" period after TA of 2 hours
(Model 2). In Model 1, Pdc declined significantly with length of awake time (P =
0.000), and showed higher Pdc with males (P = 0.098), although this sex
difference was not observed after 2 hours (Model 2). Both models showed
significantly higher Pdc in Asians than in non-Asians (P = 0.000) and increased
Pdc with age (P = 0.048, P = 0.001). CONCLUSIONS: Baseline corneal epithelial
barrier function increases after overnight sleep and varies significantly by
ethnicity and age.
PMID- 25118262
TI - Posterior pole asymmetry analyses of retinal thickness of upper and lower sectors
and their association with peak retinal nerve fiber layer thickness in healthy
young eyes.
AB - PURPOSE: To determine the symmetry of the retinal thicknesses (RT) between the 32
pairs of superior and inferior sectors by posterior pole asymmetrical analysis
(PPAA) of the spectral-domain optical coherence tomographic (SD-OCT) images in
healthy eyes. In addition, to determine their association with the position of
the peak retinal nerve fiber layer (RNFL) thickness. METHODS: A prospective,
observational, cross-sectional study of 64 right eyes. The Spectralis SD-OCT was
used to obtain the images, and the PPAA determined the RT of the 64 cells within
the central 24 degrees area. The program also compared the thicknesses of
corresponding cells across the fovea-disc axis. Circular scans were used to
measure the supra- and infratemporal RNFL peak angle differences (PADs). The
relationships between the RT of the corresponding cells and the relationship
between the differences of the RT of the corresponding cells and PAD were
investigated by linear regression analysis. RESULTS: The mean differences between
the RT of corresponding cells ranged from 3.1 to 23.2 MUm. The RT of all upper
cells were significantly correlated with the RT of the corresponding lower cells
(R = 0.45-0.97, P < 0.001). The coefficients of correlation between the
corresponding pairs of central- and temporal-macular cells were higher than that
of the peripheral and nasal-macular cells. The differences of the pairs of nasal
macular cells RT were significantly correlated with the PAD. CONCLUSIONS: The
symmetry of the RT between the upper and lower cells was high in the central and
temporal-macular areas but not in the peripheral and nasal-macular areas.
(www.umin.ac.jp/ctr number, UMIN000006040.).
PMID- 25118263
TI - Quantitative analysis of functional changes caused by pinhole glasses.
AB - PURPOSE: To quantify the visual functional changes caused by pinhole glasses.
METHODS: Healthy subjects underwent ophthalmic examinations including uncorrected
distance visual acuity (UDVA) and corrected near visual acuity (CNVA), pupil
size, depth of focus (DOF), accommodative amplitude, visual field (VF) test,
contrast sensitivity (CS), and stereopsis. Subjects underwent the same
examinations while wearing pinhole glasses 1 week later. RESULTS: Forty-eight
eyes of 48 subjects (24 male and 24 female) with a mean age of 35.5+/-6.7 years
and a mean spherical equivalent of -2.4+/-3.3 diopters (D) were enrolled. The
pinhole glasses significantly improved UDVA and CNVA (logMAR) from 0.44+/-0.46
and 0.26+/-0.40 to 0.19+/-0.25 and 0.14+/-0.22, respectively. The pinhole glasses
markedly enlarged pupils from 3.6+/-0.5 mm photopic size to 6.0+/-0.5 mm, very
close to the mesopic size of 6.2+/-0.6 mm. Mean DOF and accommodative amplitude
also significantly increased by approximately 50%, while VF featured a general
reduction of sensitivity. Mean deviation (MD) significantly decreased from
0.48+/-1.57 to -4.22+/-1.66 dB, and visual field index (VFI) decreased from
99.4+/-0.7% to 98.4+/-1.3%. The CS decreased significantly at all four spatial
frequencies, and stereopsis deteriorated with pinhole glasses. CONCLUSIONS: The
pinhole glasses improved visual acuity, DOF, and accommodative amplitude;
however, they resulted in decreased visual quality including general reduction of
VF sensitivity, CS, and stereopsis. Therefore, particular attention is needed
when wearing pinhole glasses while driving, playing sports, or working with
instruments. (ClinicalTrials.gov number, NCT02111356.).
PMID- 25118264
TI - Generation and characterization of a murine model of Bietti crystalline
dystrophy.
AB - PURPOSE: Bietti crystalline dystrophy (BCD) is a rare, autosomal recessive,
progressive, degenerative eye disease caused by mutations in the CYP4V2 gene, for
which no treatments are currently available. Cyp4v3 is the murine ortholog to
CYP4V2, and to better understand the molecular pathogenesis of this disease we
have established a Cyp4v3-null mouse line. METHODS: Cyp4v3(-/-) mice were
generated by homologous recombination in embryonic stem cells. Ocular morphologic
characteristics were evaluated via fundus imaging, plasma lipid profiling, and
histologic analysis via Oil Red O reactivity, hematoxylin and eosin staining, and
transmission electron microscopy. RESULTS: The Cyp4v3(-/-) mouse recapitulates
the characteristic features of corneoretinal crystal accumulation and systemic
dyslipidemia seen in BCD. The Cyp4v3(-/-) mice behave normally and are viable and
fertile when maintained under specific pathogen-free (SPF) housing conditions.
CONCLUSIONS: Cyp4v3(-/-) mice represent a promising preclinical model that may be
used to better understand the disease etiology and to evaluate pharmacotherapies
for this devastating condition.
PMID- 25118266
TI - Schlemm's canal expands after trabeculectomy in patients with primary angle
closure glaucoma.
AB - PURPOSE: To evaluate the in vivo changes in the Schlemm's canal (SC) in patients
with primary angle-closure glaucoma (PACG) after trabeculectomy using spectral
domain optical coherence tomography (SD-OCT). METHODS: Forty eyes of 40 patients
with PACG who underwent trabeculectomy were included. All participants underwent
SD-OCT. The diameter and area of SC were examined and measured before and within
1 month after trabeculectomy. All SD-OCT images were processed using adaptive
compensation algorithm to improve contrast and image quality. Multivariate linear
regression analysis was performed for predictors of percentage change in the mean
SC diameter and area. RESULTS: The mean age of participants was 60.5 +/- 14.6
years. Adaptive compensation significantly increased the percentage of sections
in which SC was observable in the subjects studied from 52.5% (21/40) to 75.0%
(30/40), which has acceptable intraobserver and interobserver repeatability.
There was a significant increase in the SC diameter and area at the follow-up
examination compared with the baseline value (SC diameter: 34.2 +/- 6.2 MUm vs.
28.4 +/- 6.1 MUm; SC area: 8117 +/- 1942 MUm(2) vs. 5200 +/- 996 MUm(2); all P <
0.001). After multivariate analysis, the only variable related to changes in SC
was percentage change in IOP (SC diameter, P = 0.002; SC area, P < 0.001). In
addition, the magnitude of the change in the SC area also correlated with angle
opening distance at 750 MUm from the scleral spur at baseline. CONCLUSIONS:
Expansion of SC was observed after trabeculectomy in PACG patients. The degree of
SC expansion was related to the extent of the IOP decrease.
PMID- 25118267
TI - A topographical relationship between visual field defects and optic radiation
changes in glaucoma.
AB - PURPOSE: To investigate the topographic relationship between glaucomatous retinal
ganglion cell loss and changes in the optic radiation (OR) using diffusion tensor
imaging (DTI). METHODS: A cross-sectional study was completed on nine patients
with primary open angle glaucoma and nine age- and sex-matched controls. Glaucoma
patients with binocular, symmetrical superior, or inferior visual hemifield
defects were selected. A comparative DTI analysis was conducted between OR fibers
connected to the affected and unaffected visual hemifield in the glaucoma group
and corresponding OR in the control group. RESULTS: There was a significantly
lower number of fiber bundles in the affected OR compared with unaffected OR and
controls (P < 0.01). Radial diffusivity was similar between the affected and
unaffected OR (P = 0.39), but higher in both groups compared with controls (P <
0.01). There was no difference in axial diffusivity among all groups. As a
consequence, fractional anisotropy was lower and mean diffusivity was higher in
the affected and unaffected OR compared with controls. CONCLUSIONS: A significant
loss of OR fibers connected to the severely damaged part of the optic nerve head,
but not the fibers connected to the relatively spared retinal hemifield shows a
direct relationship between retinal neuronal damage and functionally connected OR
fibers in glaucoma. However, OR fibers connected to the relatively preserved
visual hemifield in the glaucoma subjects still showed changes in radial
diffusivity compared with controls, suggesting possible early dysfunction. Our
results support the notion that glaucoma is a neurodegenerative disease involving
the posterior visual pathway.
PMID- 25118265
TI - Loss of outer retinal neurons and circuitry alterations in the DBA/2J mouse.
AB - PURPOSE: The DBA/2J mouse line develops essential iris atrophy, pigment
dispersion, and glaucomatous age-related changes, including an increase of IOP,
optic nerve atrophy, and retinal ganglion cell (RGC) death. The aim of this study
was to evaluate possible morphological changes in the outer retina of the DBA/2J
mouse concomitant with disease progression and aging, based on the reduction of
both the a- and b-waves and photopic flicker ERGs in this mouse line. METHODS:
Vertically sectioned DBA/2J mice retinas were evaluated at 3, 8, and 16 months of
age using photoreceptor, horizontal, and bipolar cell markers. Sixteen-month-old
C57BL/6 mice retinas were used as controls. RESULTS: The DBA/2J mice had outer
retinal degeneration at all ages, with the most severe degeneration in the oldest
retinas. At 3 months of age, the number of photoreceptor cells and the thickness
of the OPL were reduced. In addition, there was a loss of horizontal and ON
bipolar cell processes. At 8 months of age, RGC degeneration occurred in patches,
and in the outer retina overlying these patches, cone morphology was impaired
with a reduction in size as well as loss of outer segments and growth of
horizontal and bipolar cell processes into the outer nuclear layer. At 16 months
of age, connectivity between photoreceptors and horizontal and bipolar cell
processes overlying these patches was lost. CONCLUSIONS: Retinal degeneration in
DBA/2J mice includes photoreceptor death, loss of bipolar and horizontal cell
processes, and loss of synaptic contacts in an aging-dependent manner.
PMID- 25118268
TI - Mitochondrial haplogroups are associated with severity of diabetic retinopathy.
AB - PURPOSE: To determine if specific mitochondrial haplogroups associate with
nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic
retinopathy (PDR). METHODS: Deidentified medical records for Caucasian patients
with diabetic retinopathy (DR; 153 NPDR and 138 PDR) were obtained from BioVU,
Vanderbilt University's electronic, deidentified DNA databank. An independent
cohort of Caucasian patients with DR (44 NPDR and 57 PDR) from the Vanderbilt Eye
Institute (VEI) was used for validation. We tested for an association between
mitochondrial haplogroups and PDR among patients with DR. RESULTS: In the BioVU
cohort, PDR frequency among Caucasian DR patients differed significantly by
mitochondrial haplogroup (P = 0.027). Replication in the VEI cohort confirmed
this association (P = 0.0064). In the combined cohort, patients from the common
haplogroup H were more likely to have PDR (odds ratio [OR] = 2.0 [95% confidence
interval (CI) = 1.3-3.0], P = 0.0012), while patients from haplogroup Uk were
less likely to have PDR (OR = 0.5 [95% CI = 0.3-0.8], P = 0.0049). In logistic
regression analyses, the addition of diabetes duration, hemoglobin A1c (HgbA1c)
levels, and hypertension had no effect on the associations of haplogroups H and
Uk with PDR. CONCLUSIONS: In this study, DR patients from mitochondrial
haplogroup H were more likely to have PDR, while DR patients from haplogroup Uk
were less likely to have PDR. The association was independent of the major
clinical variables affecting PDR. The mitochondrial haplogroups were as strong a
risk factor for PDR as were elevated HgbA1c levels.
PMID- 25118271
TI - Glycopeptide use is associated with increased mortality in Enterococcus faecalis
bacteraemia--authors' response.
PMID- 25118272
TI - Science and culture: dangerous doilies. Interview by Rebecca Horne.
PMID- 25118270
TI - Homogeneity of antimicrobial policy, yet heterogeneity of antimicrobial
resistance: antimicrobial non-susceptibility among 108,717 clinical isolates from
primary, secondary and tertiary care patients in London.
AB - OBJECTIVES: We examined the 4 year trend in antimicrobial susceptibilities and
prescribing across levels of care at two London teaching hospitals and their
multisite renal unit, and for the surrounding community. METHODS: Laboratory and
pharmacy information management systems were interrogated, with antimicrobial use
and susceptibilities analysed between hospitals, within hospitals and over time.
RESULTS: A total of 108,717 isolates from 71,687 patients were identified, with
significant differences (at P < 0.05) in antimicrobial susceptibility between and
within hospitals. Across the 4 years, rates of ESBL-/AmpC-producing
Enterobacteriaceae ranged from 6.4% to 10.7% among community isolates, 17.8% to
26.9% at ward level and 25.2% to 52.5% in critical care. Significant variations
were also demonstrated in glycopeptide-resistant enterococci (ward level 6.2%
17.4%; critical care 21.9%-56.3%), MRSA (ward level 18.5%-38.2%; critical care
12.5%-47.9%) and carbapenem-resistant Pseudomonas spp. (ward level 8.3%-16.9%;
critical care 19.9%-53.7%). Few instances of persistently higher resistance were
seen between the hospitals in equivalent cohorts, despite persistently higher
antimicrobial use in Hospital 1 than Hospital 2. We found significant
fluctuations in non-susceptibility year on year across the cohorts, but with few
persistent trends. CONCLUSIONS: The marked heterogeneity of antimicrobial
susceptibilities between hospitals, within hospitals and over time demands
detailed, standardized surveillance and appropriate benchmarking to identify
possible drivers and effective interventions. Homogeneous antimicrobial policies
are unlikely to continue to be suitable as individual hospitals join hospital
networks, and policies should be tailored to local resistance rates, at least at
the hospital level, and possibly with finer resolution, particularly for critical
care.
PMID- 25118274
TI - Fungal polyketide engineering comes of age.
PMID- 25118275
TI - PIP5K1alpha inhibition as a therapeutic strategy for prostate cancer.
PMID- 25118269
TI - Genetic variants associated with severe retinopathy of prematurity in extremely
low birth weight infants.
AB - PURPOSE: To determine genetic variants associated with severe retinopathy of
prematurity (ROP) in a candidate gene cohort study of US preterm infants.
METHODS: Preterm infants in the discovery cohort were enrolled through the Eunice
Kennedy Shriver National Institute of Child Health and Human Development Neonatal
Research Network, and those in the replication cohort were from the University of
Iowa. All infants were phenotyped for ROP severity. Because of differences in the
durations of enrollment between cohorts, severe ROP was defined as threshold
disease in the discovery cohort and as threshold disease or type 1 ROP in the
replication cohort. Whole genome amplified DNA from stored blood spot samples
from the Neonatal Research Network biorepository was genotyped using an Illumina
GoldenGate platform for candidate gene single nucleotide polymorphisms (SNPs)
involving angiogenic, developmental, inflammatory, and oxidative pathways. Three
analyses were performed to determine significant epidemiologic variables and SNPs
associated with levels of ROP severity. Analyses controlled for multiple
comparisons, ancestral eigenvalues, family relatedness, and significant
epidemiologic variables. Single nucleotide polymorphisms significantly associated
with ROP severity from the discovery cohort were analyzed in the replication
cohort and in meta-analysis. RESULTS: Eight hundred seventeen infants in the
discovery cohort and 543 in the replication cohort were analyzed. Severe ROP
occurred in 126 infants in the discovery and in 14 in the replication cohort. In
both cohorts, ventilation days and seizure occurrence were associated with severe
ROP. After controlling for significant factors and multiple comparisons, two
intronic SNPs in the gene BDNF (rs7934165 and rs2049046, P < 3.1 * 10(-5)) were
associated with severe ROP in the discovery cohort and were not associated with
severe ROP in the replication cohort. However, when the cohorts were analyzed
together in an exploratory meta-analysis, rs7934165 increased in associated
significance with severe ROP (P = 2.9 * 10(-7)). CONCLUSIONS: Variants in BDNF
encoding brain-derived neurotrophic factor were associated with severe ROP in a
large candidate gene study of infants with threshold ROP.
PMID- 25118279
TI - Imaging of the cerebello-pontine angle.
PMID- 25118276
TI - KLRG+ invariant natural killer T cells are long-lived effectors.
AB - Immunological memory has been regarded as a unique feature of the adaptive immune
response mediated in an antigen-specific manner by T and B lymphocytes. However,
natural killer (NK) cells and gammadeltaT cells, which traditionally are
classified as innate immune cells, have been shown in recent studies to have
hallmark features of memory cells. Invariant NKT cell (iNKT cell)-mediated
antitumor effects indicate that iNKT cells are activated in vivo by vaccination
with iNKT cell ligand-loaded CD1d(+) cells, but not by vaccination with unbound
NKT cell ligand. In such models, it previously was thought that the numbers of
IFN-gamma-producing cells in the spleen returned to the basal level around 1 wk
after the vaccination. In the current study, we demonstrate the surprising
presence of effector memory-like iNKT cells in the lung. We found long-term
antitumor activity in the lungs of mice was enhanced after vaccination with iNKT
cell ligand-loaded dendritic cells. Further analyses showed that the KLRG1(+)
(Killer cell lectin-like receptor subfamily G, member 1-positive) iNKT cells
coexpressing CD49d and granzyme A persisted for several months and displayed a
potent secondary response to cognate antigen. Finally, analyses of CDR3beta by
RNA deep sequencing demonstrated that some particular KLRG1(+) iNKT-cell clones
accumulated, suggesting the selection of certain T-cell receptor repertoires by
an antigen. The current findings identifying effector memory-like KLRG1(+) iNKT
cells in the lung could result in a paradigm shift regarding the basis of newly
developed extrathymic iNKT cells and could contribute to the future development
of antitumor immunotherapy by uniquely energizing iNKT cells.
PMID- 25118278
TI - Engineered kinase activation reveals unique morphodynamic phenotypes and
associated trafficking for Src family isoforms.
AB - The Src kinase family comprises nine homologous members whose distinct expression
patterns and cellular distributions indicate that they have unique roles. These
roles have not been determined because genetic manipulation has not produced
clearly distinct phenotypes, and the kinases' homology complicates generation of
specific inhibitors. Through insertion of a modified FK506 binding protein
(insertable FKBP12, iFKBP) into the protein kinase isoforms Fyn, Src, Lyn, and
Yes, we engineered kinase analogs that can be activated within minutes in living
cells (RapR analogs). Combining our RapR analogs with computational tools for
quantifying and characterizing cellular dynamics, we demonstrate that Src family
isoforms produce very different phenotypes, encompassing cell spreading,
polarized motility, and production of long, thin cell extensions. Activation of
Src and Fyn led to patterns of kinase translocation that correlated with
morphological changes in temporally distinct stages. Phenotypes were dependent on
N-terminal acylation, not on Src homology 3 (SH3) and Src homology 2 (SH2)
domains, and correlated with movement between a perinuclear compartment,
adhesions, and the plasma membrane.
PMID- 25118277
TI - Immature truncated O-glycophenotype of cancer directly induces oncogenic
features.
AB - Aberrant expression of immature truncated O-glycans is a characteristic feature
observed on virtually all epithelial cancer cells, and a very high frequency is
observed in early epithelial premalignant lesions that precede the development of
adenocarcinomas. Expression of the truncated O-glycan structures Tn and sialyl-Tn
is strongly associated with poor prognosis and overall low survival. The genetic
and biosynthetic mechanisms leading to accumulation of truncated O-glycans are
not fully understood and include mutation or dysregulation of
glycosyltransferases involved in elongation of O-glycans, as well as relocation
of glycosyltransferases controlling initiation of O-glycosylation from Golgi to
endoplasmic reticulum. Truncated O-glycans have been proposed to play functional
roles for cancer-cell invasiveness, but our understanding of the biological
functions of aberrant glycosylation in cancer is still highly limited. Here, we
used exome sequencing of most glycosyltransferases in a large series of primary
and metastatic pancreatic cancers to rule out somatic mutations as a cause of
expression of truncated O-glycans. Instead, we found hypermethylation of core 1
beta3-Gal-T-specific molecular chaperone, a key chaperone for O-glycan
elongation, as the most prevalent cause. We next used gene editing to produce
isogenic cell systems with and without homogenous truncated O-glycans that
enabled, to our knowledge, the first polyomic and side-by-side evaluation of the
cancer O-glycophenotype in an organotypic tissue model and in xenografts. The
results strongly suggest that truncation of O-glycans directly induces oncogenic
features of cell growth and invasion. The study provides support for targeting
cancer-specific truncated O-glycans with immunotherapeutic measures.
PMID- 25118280
TI - Interaction of HIV-1 Nef protein with the host protein Alix promotes lysosomal
targeting of CD4 receptor.
AB - Nef is an accessory protein of human immunodeficiency viruses that promotes viral
replication and progression to AIDS through interference with various host
trafficking and signaling pathways. A key function of Nef is the down-regulation
of the coreceptor CD4 from the surface of the host cells. Nef-induced CD4 down
regulation involves at least two independent steps as follows: acceleration of
CD4 endocytosis by a clathrin/AP-2-dependent pathway and targeting of
internalized CD4 to multivesicular bodies (MVBs) for eventual degradation in
lysosomes. In a previous work, we found that CD4 targeting to the MVB pathway was
independent of CD4 ubiquitination. Here, we report that this targeting depends on
a direct interaction of Nef with Alix/AIP1, a protein associated with the
endosomal sorting complexes required for transport (ESCRT) machinery that assists
with cargo recruitment and intraluminal vesicle formation in MVBs. We show that
Nef interacts with both the Bro1 and V domains of Alix. Depletion of Alix or
overexpression of the Alix V domain impairs lysosomal degradation of CD4 induced
by Nef. In contrast, the V domain overexpression does not prevent cell surface
removal of CD4 by Nef or protein targeting to the canonical ubiquitination
dependent MVB pathway. We also show that the Nef-Alix interaction occurs in late
endosomes that are enriched in internalized CD4. Together, our results indicate
that Alix functions as an adaptor for the ESCRT-dependent, ubiquitin-independent
targeting of CD4 to the MVB pathway induced by Nef.
PMID- 25118281
TI - The T4 phage DNA mimic protein Arn inhibits the DNA binding activity of the
bacterial histone-like protein H-NS.
AB - The T4 phage protein Arn (Anti restriction nuclease) was identified as an
inhibitor of the restriction enzyme McrBC. However, until now its molecular
mechanism remained unclear. In the present study we used structural approaches to
investigate biological properties of Arn. A structural analysis of Arn revealed
that its shape and negative charge distribution are similar to dsDNA, suggesting
that this protein could act as a DNA mimic. In a subsequent proteomic analysis,
we found that the bacterial histone-like protein H-NS interacts with Arn,
implying a new function. An electrophoretic mobility shift assay showed that Arn
prevents H-NS from binding to the Escherichia coli hns and T4 p8.1 promoters. In
vitro gene expression and electron microscopy analyses also indicated that Arn
counteracts the gene-silencing effect of H-NS on a reporter gene. Because McrBC
and H-NS both participate in the host defense system, our findings suggest that
T4 Arn might knock down these mechanisms using its DNA mimicking properties.
PMID- 25118282
TI - Cathepsin S causes inflammatory pain via biased agonism of PAR2 and TRPV4.
AB - Serine proteases such as trypsin and mast cell tryptase cleave protease-activated
receptor-2 (PAR2) at R(36)?S(37) and reveal a tethered ligand that excites
nociceptors, causing neurogenic inflammation and pain. Whether proteases that
cleave PAR2 at distinct sites are biased agonists that also induce inflammation
and pain is unexplored. Cathepsin S (Cat-S) is a lysosomal cysteine protease of
antigen-presenting cells that is secreted during inflammation and which retains
activity at extracellular pH. We observed that Cat-S cleaved PAR2 at E(56)?T(57),
which removed the canonical tethered ligand and prevented trypsin activation. In
HEK and KNRK cell lines and in nociceptive neurons of mouse dorsal root ganglia,
Cat-S and a decapeptide mimicking the Cat-S-revealed tethered ligand-stimulated
PAR2 coupling to Galphas and formation of cAMP. In contrast to trypsin, Cat-S did
not mobilize intracellular Ca(2+), activate ERK1/2, recruit beta-arrestins, or
induce PAR2 endocytosis. Cat-S caused PAR2-dependent activation of transient
receptor potential vanilloid 4 (TRPV4) in Xenopus laevis oocytes, HEK cells and
nociceptive neurons, and stimulated neuronal hyperexcitability by adenylyl
cyclase and protein kinase A-dependent mechanisms. Intraplantar injection of Cat
S caused inflammation and hyperalgesia in mice that was attenuated by PAR2 or
TRPV4 deletion and adenylyl cyclase inhibition. Cat-S and PAR2 antagonists
suppressed formalin-induced inflammation and pain, which implicates endogenous
Cat-S and PAR2 in inflammatory pain. Our results identify Cat-S as a biased
agonist of PAR2 that causes PAR2- and TRPV4-dependent inflammation and pain. They
expand the role of PAR2 as a mediator of protease-driven inflammatory pain.
PMID- 25118283
TI - A critical role of the C-terminal segment for allosteric inhibitor-induced
aberrant multimerization of HIV-1 integrase.
AB - Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are a promising class of
antiretroviral agents for clinical development. Although ALLINIs promote aberrant
IN multimerization and inhibit IN interaction with its cellular cofactor
LEDGF/p75 with comparable potencies in vitro, their primary mechanism of action
in infected cells is through inducing aberrant multimerization of IN. Crystal
structures have shown that ALLINIs bind at the IN catalytic core domain dimer
interface and bridge two interacting subunits. However, how these interactions
promote higher-order protein multimerization is not clear. Here, we used mass
spectrometry-based protein footprinting to monitor surface topology changes in
full-length WT and the drug-resistant A128T mutant INs in the presence of ALLINI
2. These experiments have identified protein-protein interactions that extend
beyond the direct inhibitor binding site and which lead to aberrant
multimerization of WT but not A128T IN. Specifically, we demonstrate that C
terminal residues Lys-264 and Lys-266 play an important role in the inhibitor
induced aberrant multimerization of the WT protein. Our findings provide
structural clues for exploiting IN multimerization as a new, attractive
therapeutic target and are expected to facilitate development of improved
inhibitors.
PMID- 25118284
TI - Amyloid-beta peptide-specific DARPins as a novel class of potential therapeutics
for Alzheimer disease.
AB - Passive immunization with anti-amyloid-beta peptide (Abeta) antibodies is
effective in animal models of Alzheimer disease. With the advent of efficient in
vitro selection technologies, the novel class of designed ankyrin repeat proteins
(DARPins) presents an attractive alternative to the immunoglobulin scaffold.
DARPins are small and highly stable proteins with a compact modular architecture
ideal for high affinity protein-protein interactions. In this report, we describe
the selection, binding profile, and epitope analysis of Abeta-specific DARPins.
We further showed their ability to delay Abeta aggregation and prevent Abeta
mediated neurotoxicity in vitro. To demonstrate their therapeutic potential in
vivo, mono- and trivalent Abeta-specific DARPins (D23 and 3*D23) were infused
intracerebroventricularly into the brains of 11-month-old Tg2576 mice over 4
weeks. Both D23 and 3*D23 treatments were shown to result in improved cognitive
performance and reduced soluble Abeta levels. These findings demonstrate the
therapeutic potential of Abeta-specific DARPins for the treatment of Alzheimer
disease.
PMID- 25118286
TI - High-throughput analysis of ultrasonication-forced amyloid fibrillation reveals
the mechanism underlying the large fluctuation in the lag time.
AB - Amyloid fibrils form in supersaturated solutions of precursor proteins by a
nucleation and growth mechanism characterized by a lag time. Although the lag
time provides a clue to understanding the complexity of nucleation events, its
long period and low reproducibility have been obstacles for exact analysis.
Ultrasonication is known to effectively break supersaturation and force
fibrillation. By constructing a Handai amyloid burst inducer, which combines a
water bath-type ultrasonicator and a microplate reader, we examined the
ultrasonication-forced fibrillation of several proteins, with a focus on the
fluctuation in the lag time. Amyloid fibrillation of hen egg white lysozyme was
examined at pH 2.0 in the presence of 1.0-5.0 M guanidine hydrochloride (GdnHCl),
in which the dominant species varied from the native to denatured conformations.
Although fibrillation occurred at various concentrations of GdnHCl, the lag time
varied largely, with a minimum being observed at ~3.0 M, the concentration at
which GdnHCl-dependent denaturation ended. The coefficient of variation of the
lag time did not depend significantly on the GdnHCl concentration and was 2-fold
larger than that of the ultrasonication-dependent oxidation of iodide, a simple
model reaction. These results suggest that the large fluctuation observed in the
lag time for amyloid fibrillation originated from a process associated with a
common amyloidogenic intermediate, which may have been a relatively compact
denatured conformation. We also suggest that the Handai amyloid burst inducer
system will be useful for studying the mechanism of crystallization of proteins
because proteins form crystals by the same mechanism as amyloid fibrils under
supersaturation.
PMID- 25118285
TI - Ubiquitin-specific protease 7 regulates nucleotide excision repair through
deubiquitinating XPC protein and preventing XPC protein from undergoing
ultraviolet light-induced and VCP/p97 protein-regulated proteolysis.
AB - Ubiquitin specific protease 7 (USP7) is a known deubiquitinating enzyme for tumor
suppressor p53 and its downstream regulator, E3 ubiquitin ligase Mdm2. Here we
report that USP7 regulates nucleotide excision repair (NER) via deubiquitinating
xeroderma pigmentosum complementation group C (XPC) protein, a critical damage
recognition factor that binds to helix-distorting DNA lesions and initiates NER.
XPC is ubiquitinated during the early stage of NER of UV light-induced DNA
lesions. We demonstrate that transiently compromising cellular USP7 by siRNA and
chemical inhibition leads to accumulation of ubiquitinated forms of XPC, whereas
complete USP7 deficiency leads to rapid ubiquitin-mediated XPC degradation upon
UV irradiation. We show that USP7 physically interacts with XPC in vitro and in
vivo. Overexpression of wild-type USP7, but not its catalytically inactive or
interaction-defective mutants, reduces the ubiquitinated forms of XPC.
Importantly, USP7 efficiently deubiquitinates XPC-ubiquitin conjugates in
deubiquitination assays in vitro. We further show that valosin-containing protein
(VCP)/p97 is involved in UV light-induced XPC degradation in USP7-deficient
cells. VCP/p97 is readily recruited to DNA damage sites and colocalizes with XPC.
Chemical inhibition of the activity of VCP/p97 ATPase causes an increase in
ubiquitinated XPC on DNA-damaged chromatin. Moreover, USP7 deficiency severely
impairs the repair of cyclobutane pyrimidine dimers and, to a lesser extent,
affects the repair of 6-4 photoproducts. Taken together, our findings uncovered
an important role of USP7 in regulating NER via deubiquitinating XPC and by
preventing its VCP/p97-regulated proteolysis.
PMID- 25118287
TI - The Toxoplasma pseudokinase ROP5 is an allosteric inhibitor of the immunity
related GTPases.
AB - The Red Queen hypothesis proposes that there is an evolutionary arms race between
host and pathogen. One possible example of such a phenomenon could be the
recently discovered interaction between host defense proteins known as immunity
related GTPases (IRGs) and a family of rhoptry pseudokinases (ROP5) expressed by
the protozoan parasite, Toxoplasma gondii. Mouse IRGs are encoded by an extensive
and rapidly evolving family of over 20 genes. Similarly, the ROP5 family is
highly polymorphic and consists of 4-10 genes, depending on the strain of
Toxoplasma. IRGs are known to be avidly bound and functionally inactivated by
ROP5 proteins, but the molecular basis of this interaction/inactivation has not
previously been known. Here we show that ROP5 uses a highly polymorphic surface
to bind adjacent to the nucleotide-binding domain of an IRG and that this
produces a profound allosteric change in the IRG structure. This has two dramatic
effects: 1) it prevents oligomerization of the IRG, and 2) it alters the
orientation of two threonine residues that are targeted by the Toxoplasma Ser/Thr
kinases, ROP17 and ROP18. ROP5s are highly specific in the IRGs that they will
bind, and the fact that it is the most highly polymorphic surface of ROP5 that
binds the IRG strongly supports the notion that these two protein families are co
evolving in a way predicted by the Red Queen hypothesis.
PMID- 25118288
TI - Shock wave treatment enhances cell proliferation and improves wound healing by
ATP release-coupled extracellular signal-regulated kinase (ERK) activation.
AB - Shock wave treatment accelerates impaired wound healing in diverse clinical
situations. However, the mechanisms underlying the beneficial effects of shock
waves have not yet been fully revealed. Because cell proliferation is a major
requirement in the wound healing cascade, we used in vitro studies and an in vivo
wound healing model to study whether shock wave treatment influences
proliferation by altering major extracellular factors and signaling pathways
involved in cell proliferation. We identified extracellular ATP, released in an
energy- and pulse number-dependent manner, as a trigger of the biological effects
of shock wave treatment. Shock wave treatment induced ATP release, increased
Erk1/2 and p38 MAPK activation, and enhanced proliferation in three different
cell types (C3H10T1/2 murine mesenchymal progenitor cells, primary human adipose
tissue-derived stem cells, and a human Jurkat T cell line) in vitro. Purinergic
signaling-induced Erk1/2 activation was found to be essential for this
proliferative effect, which was further confirmed by in vivo studies in a rat
wound healing model where shock wave treatment induced proliferation and
increased wound healing in an Erk1/2-dependent fashion. In summary, this report
demonstrates that shock wave treatment triggers release of cellular ATP, which
subsequently activates purinergic receptors and finally enhances proliferation in
vitro and in vivo via downstream Erk1/2 signaling. In conclusion, our findings
shed further light on the molecular mechanisms by which shock wave treatment
exerts its beneficial effects. These findings could help to improve the clinical
use of shock wave treatment for wound healing.
PMID- 25118289
TI - Regulation of the extrinsic apoptotic pathway by microRNA-21 in alcoholic liver
injury.
AB - IL-6/Stat3 is associated with the regulation of transcription of key cellular
regulatory genes (microRNAs) during different types of liver injury. This study
evaluated the role of IL-6/Stat3 in regulating miRNA and miR-21 in alcoholic
liver disease. By microarray, we identified that ethanol feeding significantly up
regulated 0.8% of known microRNAs in mouse liver compared with controls,
including miR-21. Similarly, the treatment of normal human hepatocytes (N-Heps)
and hepatic stellate cells (HSCs) with ethanol and IL-6 significantly increased
miR-21 expression. Overexpression of miR-21 decreased ethanol-induced apoptosis
in both N-Heps and HSCs. The expression level of miR-21 was significantly
increased after Stat3 activation in N-Heps and HSCs, in support of the concept
that the 5'-promoter region of miR-21 is regulated by Stat3. Using real time PCR,
we confirmed that miR-21 activation is associated with ethanol-linked Stat3
binding of the miR-21 promoter. A combination of bioinformatics, PCR array, dual
luciferase reporter assay, and Western blot analysis revealed that Fas ligand
(TNF superfamily, member 6) (FASLG) and death receptor 5 (DR5) are the direct
targets of miR-21. Furthermore, inhibition of miR-21 by specific Vivo-Morpholino
and knock-out of IL-6 in ethanol-treated mice also increased the expression of
DR5 and FASLG in vivo during alcoholic liver injury. The identification of miR-21
as an important regulator of hepatic cell survival, transformation, and
remodeling in vitro, as well as its upstream modulators and downstream targets,
will provide insight into the involvement of altered miRNA expression in
contributing to alcoholic liver disease progression and testing novel therapeutic
approaches for human alcoholic liver diseases.
PMID- 25118292
TI - Simpson's paradox: how performance measurement can fail even with perfect risk
adjustment.
PMID- 25118290
TI - Antiparallel triple-strand architecture for prefibrillar Abeta42 oligomers.
AB - Abeta42 oligomers play key roles in the pathogenesis of Alzheimer disease, but
their structures remain elusive partly due to their transient nature. Here, we
show that Abeta42 in a fusion construct can be trapped in a stable oligomer
state, which recapitulates characteristics of prefibrillar Abeta42 oligomers and
enables us to establish their detailed structures. Site-directed spin labeling
and electron paramagnetic resonance studies provide structural restraints in
terms of side chain mobility and intermolecular distances at all 42 residue
positions. Using these restraints and other biophysical data, we present a novel
atomic-level oligomer model. In our model, each Abeta42 protein forms a single
beta-sheet with three beta-strands in an antiparallel arrangement. Each beta
sheet consists of four Abeta42 molecules in a head-to-tail arrangement. Four beta
sheets are packed together in a face-to-back fashion. The stacking of identical
segments between different beta-sheets within an oligomer suggests that
prefibrillar oligomers may interconvert with fibrils via strand rotation, wherein
beta-strands undergo an ~90 degrees rotation along the strand direction. This
work provides insights into rational design of therapeutics targeting the process
of interconversion between toxic oligomers and non-toxic fibrils.
PMID- 25118291
TI - A sensory complex consisting of an ATP-binding cassette transporter and a two
component regulatory system controls bacitracin resistance in Bacillus subtilis.
AB - Resistance against antimicrobial peptides in many Firmicutes bacteria is mediated
by detoxification systems that are composed of a two-component regulatory system
(TCS) and an ATP-binding cassette (ABC) transporter. The histidine kinases of
these systems depend entirely on the transporter for sensing of antimicrobial
peptides, suggesting a novel mode of signal transduction where the transporter
constitutes the actual sensor. The aim of this study was to investigate the
molecular mechanisms of this unusual signaling pathway in more detail, using the
bacitracin resistance system BceRS-BceAB of Bacillus subtilis as an example. To
analyze the proposed communication between TCS and the ABC transporter, we
characterized their interactions by bacterial two-hybrid analyses and could show
that the permease BceB and the histidine kinase BceS interact directly. In vitro
pulldown assays confirmed this interaction, which was found to be independent of
bacitracin. Because it was unknown whether BceAB-type transporters could detect
their substrate peptides directly or instead recognized the peptide-target
complex in the cell envelope, we next analyzed substrate binding by the transport
permease, BceB. Direct and specific binding of bacitracin by BceB was
demonstrated by surface plasmon resonance spectroscopy. Finally, in vitro signal
transduction assays indicated that complex formation with the transporter
influenced the autophosphorylation activity of the histidine kinase. Taken
together, our findings clearly show the existence of a sensory complex composed
of TCS and ABC transporters and provide the first functional insights into the
mechanisms of stimulus perception, signal transduction, and antimicrobial
resistance employed by Bce-like detoxification systems.
PMID- 25118294
TI - Predictive markers of radiotherapy-induced rectal cancer regression.
AB - Patients with locally advanced rectal cancer receive preoperative radiotherapy to
reduce the probability of recurrence and to possibly improve overall survival.
However, this appears dependent on the extent of histological tumour regression
seen in the resected bowel, which can be highly variable between individuals. No
predictive marker that can stratify patient management in this regard is
currently available. Experimental data implicates a variety of factors that are
involved in the DNA damage response following radiation injury, tumour tissue
oxygenation, autoimmune antitumour response triggered by radiotherapy and in the
pathogenesis of colorectal cancer, as potential indicators of radiation
sensitivity. These details are presented in this review, which may serve as
targets for clinical validation studies aiming to find predictors of radiotherapy
response in rectal cancer.
PMID- 25118293
TI - Alterations of insulin-like growth factor-1 receptor gene copy number and protein
expression are common in non-small cell lung cancer.
AB - AIMS: Insulin-like growth factor-1 receptor (IGF1R) is a tyrosine kinase membrane
receptor involved in tumourigenesis that may be a potential therapeutic target.
We aimed to investigate the incidence and prognostic significance of alterations
in IGF1R copy number, and IGF1R protein expression in resected primary non-small
cell lung cancer (NSCLC), and lymph node metastases. METHODS: IGF1R gene copy
number status was evaluated by chromogenic silver in situ hybridisation and IGF1R
protein expression was evaluated by immunohistochemistry in tissue microarray
sections from a retrospective cohort of 309 surgically resected NSCLCs and
results were compared with clinicopathological features, including EGFR and KRAS
mutational status and patient survival. RESULTS: IGF1R gene copy number status
was positive (high polysomy or amplification) in 29.2% of NSCLC, and 12.1%
exhibited IGF1R gene amplification. High IGF1R expression was found in 28.3%.
There was a modest correlation between IGF1R gene copy number and protein
expression (r=0.2, p<0.05). Alterations of IGF1R gene copy number and protein
expression in primary tumours were significantly associated with alterations in
lymph node metastases (p<0.01). High IGF1R gene copy number and protein
expression was significantly higher in squamous cell carcinomas (SCC) compared
with other subtypes of NSCLC (p<0.05). There were no other associations between
IGF1R status and other clinicopathological features including patient age,
gender, smoking status, tumour size, stage, grade, EGFR or KRAS mutational status
or overall survival. CONCLUSIONS: High IGF1R gene copy number and protein
overexpression are frequent in NSCLC, particularly in SCCs, but they are not
prognostically relevant.
PMID- 25118295
TI - CXCR4 antagonist inhibits perineural invasion of adenoid cystic carcinoma.
AB - AIM: Perineural invasion and expression of CXCR4 is characteristic of adenoid
cystic carcinoma (ACC). Herein, we aimed to demonstrate CXCR4 expression in ACC,
identify its association with perineural invasion and investigate the impact of
CXCR4 inhibitor in vitro and in a murine perineural invasion model. METHODS:
Expression of CXCR4 was assessed in ACC cell lines and in human tissue. The
effects of gene knockdown using siRNA and specific blocker of CXCR4 (AMD3100)
were evaluated in vitro. A preclinical perineural invasion model was developed
using BALB/c nude mouse. The effect of AMD3100 was evaluated in vivo. RESULTS:
CXCR4 was highly expressed in aggressive strains of ACC in vitro, in the tumour
in the animal model and in the tumour of human tissue. SDF-1 expression was also
demonstrated in the nerve of murine and human tissue. Gene knockdown by siRNA and
inhibition by a CXCR4-specific inhibitor AMD3100 effectively abrogated invasion
but not proliferation of ACC in vitro. The rate of perineural invasion was
significantly decreased with AMD3100 treatment in the animal model. CONCLUSIONS:
CXCR4 is associated with perineural invasion in ACC. AMD3100, which can
effectively diminish perineural invasion of ACC, may have an adjuvant role in the
management of ACC.
PMID- 25118296
TI - Leaf mass per area is independent of vein length per area: avoiding pitfalls when
modelling phenotypic integration (reply to Blonder et al. 2014).
AB - It has been recently proposed that leaf vein length per area (VLA) is the major
determinant of leaf mass per area ( MA), and would thereby determine other traits
of the leaf economic spectrum (LES), such as photosynthetic rate per mass
(A(mass)), nitrogen concentration per mass (N(mass)) and leaf lifespan (LL). In a
previous paper we argued that this 'vein origin' hypothesis was supported only by
a mathematical model with predestined outcomes, and that we found no support for
the 'vein origin' hypothesis in our analyses of compiled data. In contrast to the
'vein origin' hypothesis, empirical evidence indicated that VLA and LMA are
independent mechanistically, and VLA (among other vein traits) contributes to a
higher photosynthetic rate per area (A(area)), which scales up to driving a
higher A(mass), all independently of LMA, N(mass) and LL. In their reply to our
paper, Blonder et al. (2014) raised questions about our analysis of their model,
but did not address our main point, that the data did not support their
hypothesis. In this paper we provide further analysis of an extended data set,
which again robustly demonstrates the mechanistic independence of LMA from VLA,
and thus does not support the 'vein origin' hypothesis. We also address the four
specific points raised by Blonder et al. (2014) regarding our analyses. We
additionally show how this debate provides critical guidance for improved
modelling of LES traits and other networks of phenotypic traits that determine
plant performance under contrasting environments.
PMID- 25118297
TI - SUMO1 in human sperm: new targets, role in motility and morphology and
relationship with DNA damage.
AB - In studies carried out previously, we demonstrated that small ubiquitin-like
modifier 1 (SUMO1) is associated with poor sperm motility when evaluated with a
protocol that reveals mostly SUMO1-ylated live sperm. Recently, with another
protocol, it has been demonstrated that SUMO is expressed in most sperm and is
related to poor morphology and motility, suggesting that sumoylation may have
multiple roles depending on its localisation and targets. We show herein, by
confocal microscopy and co-immunoprecipitation, that dynamin-related protein 1
(DRP1), Ran GTPase-activating protein 1 (RanGAP1) and Topoisomerase IIalpha,
SUMO1 targets in somatic and/or germ cells, are SUMO1-ylated in mature human
spermatozoa. DRP1 co-localises with SUMO1 in the mid-piece, whereas RanGAP1 and
Topoisomerase IIalpha in the post-acrosomal region of the head. Both SUMO1
expression and co-localisation with the three proteins were significantly higher
in morphologically abnormal sperm, suggesting that sumoylation represents a
marker of defective sperm. DRP1 sumoylation at the mid-piece level was higher in
the sperm of asthenospermic men. As in somatic cells, DRP1 sumoylation is
associated with mitochondrial alterations, this protein may represent the link
between SUMO and poor motility. As SUMO pathways are involved in responses to DNA
damage, another aim of our study was to investigate the relationship between
sumoylation and sperm DNA fragmentation (SDF). By flow cytometry, we demonstrated
that SUMO1-ylation and SDF are correlated (r=0.4, P<0.02, n=37) and most
sumoylated sperm shows DNA damage in co-localisation analysis. When SDF was
induced by stressful conditions (freezing and thawing and oxidative stress),
SUMO1-ylation increased. Following freezing and thawing, SUMO1-Topoisomerase
IIalpha co-localisation and co-immunoprecipitation increased, suggesting an
involvement in the formation/repair of DNA breakage.
PMID- 25118298
TI - CAR expression in human embryos and hESC illustrates its role in pluripotency and
tight junctions.
AB - Coxsackie virus and adenovirus receptor, CXADR (CAR), is present during
embryogenesis and is involved in tissue regeneration, cancer and intercellular
adhesion. We investigated the expression of CAR in human preimplantation embryos
and embryonic stem cells (hESC) to identify its role in early embryogenesis and
differentiation. CAR protein was ubiquitously present during preimplantation
development. It was localised in the nucleus of uncommitted cells, from the
cleavage stage up to the precursor epiblast, and corresponded with the presence
of soluble CXADR3/7 splice variant. CAR was displayed on the membrane, involving
in the formation of tight junction at compaction and blastocyst stages in both
outer and inner cells, and CAR corresponded with the full-length CAR-containing
transmembrane domain. In trophectodermal cells of hatched blastocysts, CAR was
reduced in the membrane and concentrated in the nucleus, which correlated with
the switch in RNA expression to the CXADR4/7 and CXADR2/7 splice variants. The
cells in the outer layer of hESC colonies contained CAR on the membrane and all
the cells of the colony had CAR in the nucleus, corresponding with the
transmembrane CXADR and CXADR4/7. Upon differentiation of hESC into cells
representing the three germ layers and trophoblast lineage, the expression of
CXADR was downregulated. We concluded that CXADR is differentially expressed
during human preimplantation development. We described various CAR expressions:
i) soluble CXADR marking undifferentiated blastomeres; ii) transmembrane CAR
related with epithelial-like cell types, such as the trophectoderm (TE) and the
outer layer of hESC colonies; and iii) soluble CAR present in TE nuclei after
hatching. The functions of these distinct forms remain to be elucidated.
PMID- 25118299
TI - Expression, activation, and role of AKT isoforms in the uterus.
AB - The three isoforms of AKT: AKT1, AKT2, and AKT3, are crucial regulators of both
normal and pathological cellular processes. Each of these isoforms exhibits a
high level of homology and functional redundancy with each other. However, while
being highly similar and structurally homologous, a rising amount of evidence is
showing that each isoform possesses specific targets as well as preferential
subcellular localization. The role of AKT has been studied extensively in
reproductive processes, but isoform-specific roles are yet to be fully
understood. This review will focus on the role of AKT in the uterus and its
function in processes related to cell death and proliferation such as embryo
implantation, decidualization, endometriosis, and endometrial cancer in an
isoform-centric manner. In this review, we will cover the activation of AKT in
various settings, localization of isoforms in subcellular compartments, and the
effect of isoform expression on cellular processes. To fully understand the
dynamic molecular processes taking place in the uterus, it is crucial that we
better understand the physiological role of AKT isoforms as well as their
function in the emergence of diseases.
PMID- 25118300
TI - Haplo-deficiency of ODF1/HSPB10 in mouse sperm causes relaxation of head-to-tail
linkage.
AB - The small heat shock protein ODF1/HSPB10 is essential for male fertility in mice.
Targeted deletion of Odf1 resulted in acephalic sperm in homozygous mice of mixed
background (C57BL/6J//129/Sv), whereas heterozygous animals are fully fertile. To
further elucidate the function of ODF1, we generated incipient congenic mice with
targeted deletion of Odf1 by successive backcrossing on the 129/Sv background. We
observed that fecundity of heterozygous Odf1(+/-) male mice was severely reduced
over backcross generations. However, neither aberrant sperm parameters nor sperm
anomalies could be observed. Ultra-structural analyses of sperm from incipient
congenic heterozygous Odf1(+/-) males of backcross generation N7 revealed no
obvious pathological findings. However, we observed an enlargement of the
distance between nuclear membrane and capitulum, indicating a weakening of the
sperm head-to-tail coupling. Severe male subfertility provoked by haplo
deficiency of ODF1 is therefore most probably caused by impaired head-to-tail
coupling that eventually might induce sperm decapitation on the specific
conditions of in vivo fertilisation. As subfertility in haplo-deficient ODF1 male
mice could not be diagnosed by semen analysis, it seems to be a paradigm for
unexplained infertility that is a frequent diagnosis for male fertility
impairment in humans.
PMID- 25118301
TI - Seminal plasma aids the survival and cervical transit of epididymal ram
spermatozoa.
AB - Seminal plasma purportedly plays a critical role in reproduction, but epididymal
spermatozoa are capable of fertilisation following deposition in the uterus,
calling into question the biological requirement of this substance. Through a
combination of direct observation of spermatozoa in utero using probe-based
Confocal Laser Endomicroscopy, in vivo assessment of sperm fertility and in vitro
analysis of various sperm functional parameters, this study investigated the role
of seminal plasma in spermatozoa transit through the cervix of the ewe. Following
deposition in the cervical os, epididymal spermatozoa previously exposed to
seminal plasma displayed an enhanced ability to traverse the cervix as evidenced
by both significantly higher pregnancy rates and numbers of spermatozoa observed
at the utero-tubal junction when compared with epididymal spermatozoa not
previously exposed to seminal plasma. The beneficial effect of seminal plasma on
sperm transport was clearly localised to transit through the cervix as pregnancy
rates of spermatozoa deposited directly into the uterus were unaffected by
exposure to seminal plasma. This phenomenon was not explained by changes to sperm
motion characteristics, as seminal plasma had no effect on the motility,
kinematic parameters or mitochondrial membrane potential of spermatozoa. Rather,
in vitro testing revealed that seminal plasma improved the ability of epididymal
spermatozoa to penetrate cervical mucus recovered from ewes in oestrus. These
results demonstrate that the survival and transport of ram spermatozoa through
the cervix of the ewe is not linked to their motility or velocity but rather the
presence of some cervical penetration trait conferred by exposure to seminal
plasma.
PMID- 25118302
TI - Individual commitment to a group effect: strengths and weaknesses of bovine
embryo group culture.
AB - Recently, new culture devices such as Corral and Primo Vision dishes have been
designed for the culture of human embryos to allow the combination of group
culture plus follow-up of individual embryos. Bovine inseminated oocytes were
allocated to Primo Vision dishes, Corral dishes, individual culture or classical
group culture. Blastocyst development in Primo Vision dishes was similar to
classical group culture (34.3 and 39.0% respectively), and better than Corral
dishes or individual culture (28.9 and 28.5% respectively). In Primo Vision
dishes, a higher number of 'slow' embryos developed to the blastocyst stage
compared with their individually cultured counterparts, while no differences were
observed for 'fast' embryos. 'Slow' embryos in a 'standard drop' had a higher
chance of becoming a blastocyst compared with individual culture (OR: 2.3),
whereas blastulation of 'fast' embryos was less efficient in a 'delayed drop'
than in individual culture (OR: 0.3). The number of non-cleaved embryos in Primo
Vision dishes did not negatively influence blastocyst development. Likewise,
removing non-cleaved embryos (NC removed) and regrouping the cleaved embryos
afterwards (ReGR) did not affect blastocyst development and quality compared with
group culture in Primo Vision dishes (CTRL, 31.6%, NC removed, 29.3% and ReGR,
29.6%). The experiments revealed that group culture of bovine embryos in Primo
Vision dishes is superior to individual culture, primarily because of the higher
blastocyst rate achieved by slow embryos. Non-cleaved or arrested embryos do not
hamper the ability of co-cultured bovine embryos to reach the blastocyst stage in
group culture.
PMID- 25118303
TI - Lamin A/C proteins in the spermatid acroplaxome are essential in mouse
spermiogenesis.
AB - Spermiogenesis is a complex process of terminal differentiation that is necessary
to produce mature sperm. Using protein expression profiles of mouse and human
testes generated from our previous studies, we chose to examine the actions of
lamin A/C in the current investigation. Lamin A and lamin C are isoforms of the A
type lamins that are encoded by the LMNA gene. Our results showed that lamin A/C
was expressed in the mouse testis throughout the different stages of
spermatogenesis and in mature sperm. Lamin A/C was also expressed in mouse
haploid germ cells and was found to be localized to the acroplaxome in
spermiogenesis, from round spermatids until mature spermatozoa. The decreased
expression of lamin A/C following injections of siRNA against Lmna caused a
significant increase in caudal sperm head abnormalities when compared with
negative controls. These abnormalities were characterized by increased
fragmentation of the acrosome and abnormal vesicles, which failed to fuse to the
developing acrosome. This fragmentation also caused significant alterations in
nuclear elongation and acrosome formation. Furthermore, we found that lamin A/C
interacted with the microtubule plus-end-tracking protein CLIP170. These results
suggest that lamin A/C is critical for proper structural and functional
development of the sperm acrosome and head shape.
PMID- 25118304
TI - Expression and regulation of the tumor suppressor, SEF, during folliculogenesis
in humans and mice.
AB - Similar expression to FGF (Sef or IL17-RD), is a tumor suppressor and an
inhibitor of growth factors as well as of pro-inflammatory cytokine signaling. In
this study, we examined the regulation of Sef expression by gonadotropins during
ovarian folliculogenesis. In sexually immature mice, in situ hybridization (ISH)
localized Sef gene expression to early developing oocytes and granulosa cells
(GC) but not to theca cells. Sef was also expressed in mouse ovarian endothelial
cells, in the fallopian tube epithelium as well as in adipose tissue venules. SEF
protein expression, determined by immunohistochemistry (IHC), correlated well
with Sef mRNA expression in GC, while differential expression was noticed in
oocytes. High Sef mRNA but undetectable SEF protein levels were observed in the
oocytes of primary/secondary follicles, while an inverse correlation was found in
the oocytes of preantral and small antral follicles. Sef mRNA expression dropped
after pregnant mare's serum gonadotropin (PMSG) administration, peaked at 6-8 h
after human chorionic gonadotropin (hCG) treatment, and declined by 12 h after
this treatment. ISH and IHC localized the changes to oocytes and mural GC
following PMSG treatment, whereas Sef expression increased in mural GC and
declined in granulosa-lutein cells upon hCG treatment. The ovarian expression of
SEF was confirmed using human samples. ISH localized SEF transcripts to human GC
of antral follicles but not to corpora lutea. Furthermore, SEF mRNA was detected
in human GC recovered from preovulatory follicles. These results are the first to
demonstrate SEF expression in a healthy ovary during folliculogenesis. Hormonal
regulation of its expression suggests that SEF may be an important factor
involved in intra-ovarian control mechanisms.
PMID- 25118305
TI - Comparison of Therapist-Directed and Physician-Directed Respiratory Care in COPD
Subjects With Acute Pneumonia.
AB - BACKGROUND: The purpose of this retrospective medical record review was to
compare the effects of therapist-directed (protocol RT) and physician-directed
(non-protocol RT) respiratory therapy on hospital stay and 30-d post-discharge
readmission in COPD subjects with acute bacterial pneumonia. METHODS: We reviewed
320 medical records; 244 records were usable. Information gathered included
gender, age, RT protocol type (protocol RT or non-protocol RT), hospital stay, 30
d post-discharge readmission, and disease severity score. A 3-way analysis of
variance and post hoc analysis were performed to determine the possible effects
of disease severity, age, and RT protocol type on hospital stay and the possible
interaction effects among these independent variables. A chi-square test for
independence was computed to determine whether there was an association between
RT protocol type and 30-d readmission. RESULTS: There were no significant
interaction effects among RT protocol type, age, and disease severity on hospital
stay. In addition, there were no significant effects of either RT protocol type
(P=.41) or age (P=.85) on hospital stay in our subject sample. However, as
expected, disease severity had a significant effect on hospital stay, increasing
it by a mean of 2.6 d (95% CI 0.77-4.4, P=.005). The chi-square test for
independence revealed that the frequency of 30-d readmission was significantly
associated with RT protocol type (P=.02); fewer 30-d readmissions were associated
with protocol RT. CONCLUSIONS: We interpreted the finding of no difference in
mean hospital stay between protocol and non-protocol RT to indicate that protocol
RT did not confer a disadvantage to subjects in terms of hospital stay.
Additionally, the results suggest that treatment efficacy is not sacrificed when
RT is directed by respiratory therapists rather than by physicians regardless of
disease severity and that therapist-directed protocols may have been of some
benefit in reducing 30-d post-discharge readmission.
PMID- 25118306
TI - Neonatal and adult ICU ventilators to provide ventilation in neonates, infants,
and children: a bench model study.
AB - BACKGROUND: Using a bench test model, we investigated the hypothesis that
neonatal and/or adult ventilators equipped with neonatal/pediatric modes
currently do not reliably administer pressure support (PS) in neonatal or
pediatric patient groups in either the absence or presence of air leaks. METHODS:
PS was evaluated in 4 neonatal and 6 adult ventilators using a bench model to
evaluate triggering, pressurization, and cycling in both the absence and presence
of leaks. Delivered tidal volumes were also assessed. Three patients were
simulated: a preterm infant (resistance 100 cm H2O/L/s, compliance 2 mL/cm H2O,
inspiratory time of the patient [TI] 400 ms, inspiratory effort 1 and 2 cm H2O),
a full-term infant (resistance 50 cm H2O/L/s, compliance 5 mL/cm H2O, TI 500 ms,
inspiratory effort 2 and 4 cm H2O), and a child (resistance 30 cm H2O/L/s,
compliance 10 mL/cm H2O, TI 600 ms, inspiratory effort 5 and 10 cm H2O). Two PS
levels were tested (10 and 15 cm H2O) with and without leaks and with and without
the leak compensation algorithm activated. RESULTS: Without leaks, only 2
neonatal ventilators and one adult ventilator had trigger delays under a given
predefined acceptable limit (1/8 TI). Pressurization showed high variability
between ventilators. Most ventilators showed TI in excess high enough to
seriously impair patient-ventilator synchronization (> 50% of the TI of the
subject). In some ventilators, leaks led to autotriggering and impairment of
ventilation performance, but the influence of leaks was generally lower in
neonatal ventilators. When a noninvasive ventilation algorithm was available,
this was partially corrected. In general, tidal volume was calculated too low by
the ventilators in the presence of leaks; the noninvasive ventilation algorithm
was able to correct this difference in only 2 adult ventilators. CONCLUSIONS: No
ventilator performed equally well under all tested conditions for all explored
parameters. However, neonatal ventilators tended to perform better in the
presence of leaks. These findings emphasize the need to improve algorithms for
assisted ventilation modes to better deal with situations of high airway
resistance, low pulmonary compliance, and the presence of leaks.
PMID- 25118307
TI - Subjects hospitalized with the 2009 pandemic influenza A (H1N1) virus in a
respiratory infection unit: clinical factors correlating with ICU admission.
AB - BACKGROUND: The 2009 pandemic influenza A (H1N1) virus was accompanied by high
morbidity and mortality. The aim of this study was to describe the clinical
characteristics of patients with documented 2009 influenza A (H1N1) virus
admitted to a reference chest hospital, the disease outcome, and risk factors
associated with ICU admission. METHODS: We assessed 109 subjects admitted to the
respiratory infection unit of a hospital for chest disease with signs and
symptoms of the 2009 influenza A (H1N1) virus between April 2009 and December
2010. Demographic data, comorbidities, clinical signs and symptoms, laboratory
tests, radiographic findings, treatment, and final outcomes were all recorded.
Factors associated with severe disease requiring ICU admission were determined.
RESULTS: Ninety subjects (82.5%) had laboratory-confirmed 2009 influenza A
(H1N1). Sixty-four percent of these subjects had pneumonia on admission, 26% had
respiratory failure, and 11% required care in the ICU. Dyspnea and the presence
of infiltrates on chest x-rays were the most common signs among the subjects with
H1N1. All subjects were treated with antiviral therapy, and 75% received
antibiotic treatment based on their clinical and laboratory findings. The
predictive factors of ICU admission were severe hypoxemia and lymphocytosis.
CONCLUSIONS: The outcome of subjects with influenza A (H1N1) virus infection was
influenced by the severity of the disease on admission, the subjects' underlying
conditions, and complications during hospitalization.
PMID- 25118308
TI - Use of heliox delivered via high-flow nasal cannula to treat an infant with
coronavirus-related respiratory infection and severe acute air-flow obstruction.
AB - Heliox, a helium-oxygen gas mixture, has been used for many decades to treat
obstructive pulmonary disease. The lower density and higher viscosity of heliox
relative to nitrogen-oxygen mixtures can significantly reduce airway resistance
when an anatomic upper air-flow obstruction is present and gas flow is turbulent.
Clinically, heliox can decrease airway resistance in acute asthma in adults and
children and in COPD. Heliox may also enhance the bronchodilating effects of beta
agonist administration for acute asthma. Respiratory syndromes caused by
coronavirus infections in humans range in severity from the common cold to severe
acute respiratory syndrome associated with human coronavirus OC43 and other viral
strains. In infants, coronavirus infection can cause bronchitis, bronchiolitis,
and pneumonia in variable combinations and can produce enough air-flow
obstruction to cause respiratory failure. We describe a case of coronavirus OC43
infection in an infant with severe acute respiratory distress treated with heliox
inhalation to avoid intubation.
PMID- 25118309
TI - A taxonomy for mechanical ventilation: 10 fundamental maxims.
AB - The American Association for Respiratory Care has declared a benchmark for
competency in mechanical ventilation that includes the ability to "apply to
practice all ventilation modes currently available on all invasive and
noninvasive mechanical ventilators." This level of competency presupposes the
ability to identify, classify, compare, and contrast all modes of ventilation.
Unfortunately, current educational paradigms do not supply the tools to achieve
such goals. To fill this gap, we expand and refine a previously described
taxonomy for classifying modes of ventilation and explain how it can be
understood in terms of 10 fundamental constructs of ventilator technology: (1)
defining a breath, (2) defining an assisted breath, (3) specifying the means of
assisting breaths based on control variables specified by the equation of motion,
(4) classifying breaths in terms of how inspiration is started and stopped, (5)
identifying ventilator-initiated versus patient-initiated start and stop events,
(6) defining spontaneous and mandatory breaths, (7) defining breath sequences
(8), combining control variables and breath sequences into ventilatory patterns,
(9) describing targeting schemes, and (10) constructing a formal taxonomy for
modes of ventilation composed of control variable, breath sequence, and targeting
schemes. Having established the theoretical basis of the taxonomy, we demonstrate
a step-by-step procedure to classify any mode on any mechanical ventilator.
PMID- 25118310
TI - Extracorporeal membrane oxygenation for refractory air leak in a child presenting
with bacterial tracheitis.
PMID- 25118311
TI - Asthma and adherence to inhaled corticosteroids: current status and future
perspectives.
AB - Inhaled corticosteroids (ICS) are the cornerstone of maintenance asthma therapy.
However, in spite of this, adherence to ICS remains low. The aim of this
systematic literature review was to provide an overview of the current knowledge
of adherence to ICS, effects of poor adherence, and means to improve adherence. A
total of 19 studies met the inclusion criteria: 9 focusing on the level of
adherence, 6 focusing on effects of poor adherence, and 7 focusing on
interventions to improve adherence. Three of the studies focused on more than one
of these end points. The mean level of adherence to ICS was found to be between
22 and 63%, with improvement up to and after an exacerbation. Poor adherence was
associated with youth, being African-American, having mild asthma, < 12 y of
formal education, and poor communication with the health-care provider, whereas
improved adherence was associated with being prescribed fixed-combination therapy
(ICS and long-acting beta2 agonists). Good adherence was associated with higher
FEV1, a lower percentage of eosinophils in sputum, reduction in hospitalizations,
less use of oral corticosteroids, and lower mortality rate. Overall, 24% of
exacerbations and 60% of asthma-related hospitalizations could be attributed to
poor adherence. Most studies have reported an increase in adherence following
focused interventions, followed by an improvement in quality of life, symptoms,
FEV1, and oral corticosteroid use. However, 2 studies found no difference in
health-care utilization, one observed no effect on symptoms, and one observed
more symptoms in subjects in the intervention group compared with the control
group. Good adherence to ICS in asthma improves outcome but remains low.
Interventions to improve adherence show varying results, with most studies
reporting an increase in adherence but unfortunately not necessarily an
improvement in outcome. Even following successful interventions, adherence
remains low. Further research is needed to explore barriers to adherence and
interventions for improvement.
PMID- 25118312
TI - Effects of different levels of pressure support on intra-individual breath-to
breath variability.
AB - BACKGROUND: Evidence exists that during pressure support ventilation (PSV), the
addition of an extrinsic (ie, ventilator-generated) breath-to-breath variability
(BBV) of breathing pattern improves respiratory function. If BBV is beneficial
per se, choosing the PS level that maximizes it could be considered a valid
strategy for conventional PSV. In this study, we evaluated the effect of
different PS levels on intrinsic BBV in acutely ill, mechanically ventilated
subjects to determine whether a significant relationship exists between PS level
and BBV magnitude. METHODS: Fourteen invasively mechanically ventilated subjects
were prospectively studied. PS was adjusted at 20 cm H2O and sequentially reduced
to 15, 10, and 5 cm H2O. Arterial blood gas analysis and pressure at 0.1 s after
the onset of inspiration (P0.1) were measured at each PS level. Airway and
esophageal pressure and air flow were continuously recorded. Peak inspiratory
flow, tidal volume (VT), breathing frequency, and pressure-time product (PTP)
were calculated on a breath-by-breath basis. The breathing pattern variability
was assessed by the coefficient of variation of the time series of VT, peak
inspiratory flow, and breathing frequency from ~ 60 consecutive breath cycles at
each PS level. A general linear model for repeated measures was applied, with PS
as an independent factor. A significance level of .05 was considered. RESULTS:
Despite a large inter-individual difference in all measured variables (P < .001),
the coefficient of variation was as low as 30%, and no significant differences in
the coefficient of variation of peak inspiratory flow, breathing frequency, and
VT between PS levels were observed (P > .15). Additionally, a significant
increase in P0.1, PTP, and breathing frequency (P < .01) and a reduction in VT (P
< .001) were observed with PS reduction. CONCLUSIONS: Despite a significant
increase in spontaneous activity with PS reduction, BBV was not influenced by the
PS level and was as low as 30% for all evaluated parameters.
PMID- 25118314
TI - Gender-specific differences in Adamantiades-Behcet's disease manifestations: an
analysis of the German registry and meta-analysis of data from the literature.
AB - OBJECTIVE: We investigated the effect of gender on the clinical Adamantiades
Behcet's disease (ABD) phenotype with data from the German ABD registry and a
meta-analysis from a systematic literature review. METHODS: Using the German ABD
registry data, we compared 36 clinical variables by gender (with women as the
reference category) and investigated potential effect modification by HLA-B5 or
ethnic background. The registry data were combined with those from a literature
search to calculate pooled relative risks (RRs) for variables with data from >=10
relevant datasets. RESULTS: The German ABD registry provided information for 747
subjects (58.1% males) and the systematic literature review identified another 52
datasets informing on 16 variables. Both analyses consistently revealed the
association of male gender with ocular involvement (RR 1.28 and 1.34 from the ABD
registry and meta-analysis, respectively), folliculitis (RR 1.30 and 1.26),
papulopustular lesions (RR 1.23 and 1.25), vascular involvement (RR 2.31 and
2.27), superficial (RR 2.96 and 1.63) and deep venous thromboses (RR 2.56 and
2.16) and female gender with genital ulcers (RR 0.78 and 0.92) and joint
involvement (RR 0.79 and 0.89). The ABD registry data additionally showed male
gender associated with heart involvement (RR 10.60), whereas the meta-analyses
revealed male gender associated with the pathergy test (RR 1.14) and female
gender associated with erythema nodosum (RR 0.86). HLA-B5 and Turkish or German
origin did not affect the observed associations. CONCLUSION: These analyses
support gender-associated clinical variations in ABD and in particular a
clinically meaningful risk of cardiovascular involvement for men.
PMID- 25118315
TI - The role of ultrasound in the diagnosis and management of carpal tunnel syndrome:
a new paradigm.
AB - Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy, affecting
9% of women, and it is responsible for significant morbidity and occupational
absence. Clinical assessment is used for initial diagnosis and nerve conduction
(NC) studies are currently the principal test used to confirm the diagnosis.
Sensitivity of NC studies is >85% and specificity is >95%. There is now good
evidence that US can be used as an alternative to NC studies to diagnose CTS. US
can assess the anatomy of the median nerve and also identify pathology of the
surrounding structures that may compress the nerve. Median nerve enlargement
(cross-sectional area >=10 mm(2) at the level of the pisiform bone or tunnel
inlet) is the most commonly used parameter to diagnose CTS on US, and sensitivity
has been reported to be as high as 97.9% using this parameter. US may also be
used to guide therapeutic corticosteroid injection into the carpal tunnel--thus
avoiding median nerve injury--and to objectively monitor the response to
treatment. There is now sufficient evidence to propose a new paradigm for the
diagnosis of CTS that incorporates US. US is proposed as the initial diagnostic
test in CTS based on similar sensitivity and specificity to NC studies but higher
patient acceptability, lower cost and additional capability to assess carpal
tunnel anatomy and guide injection.
PMID- 25118316
TI - Vocal fold bamboo nodes in undifferentiated connective tissue disease.
PMID- 25118313
TI - Methotrexate-mediated inhibition of nuclear factor kappaB activation by distinct
pathways in T cells and fibroblast-like synoviocytes.
AB - OBJECTIVES: Nuclear factor kappaB (NF-kappaB) is a critical activator of
inflammatory processes and MTX is one of the most commonly prescribed DMARDs for
treatment of RA. We sought to determine whether MTX inhibited NF-kappaB activity
in RA and in lymphocytes and fibroblast-like synoviocytes (FLSs) and to define
underlying mechanisms of action. METHODS: An NF-kappaB luciferase reporter
plasmid was used to measure NF-kappaB activation across experimental stimuli.
Flow cytometry was used to quantify changes in intracellular protein levels,
measure levels of reactive oxygen species and determine apoptosis. Quantitative
RT-PCR was used to identify changes in MTX target genes. RESULTS: In T cell
lines, MTX (0.1 MUM) inhibited activation of NF-kappaB via depletion of
tetrahydrobiopterin (BH4) and increased Jun-N-terminal kinase (JNK)-dependent p53
activity. Inhibitors of BH4 activity or synthesis also inhibited NF-kappaB
activation and, similar to MTX, increased JNK, p53, p21 and JUN activity.
Patients with RA expressed increased levels of phosphorylated or active RelA
(p65) compared with controls. Levels of phosphorylated RelA were reduced in
patients receiving low-dose MTX therapy. In contrast, inhibition of NF-kappaB
activation by MTX was not mediated via BH4 depletion and JNK activation in FLSs,
but rather was completely prevented by adenosine receptor antagonists.
CONCLUSION: Our findings support a model whereby distinct pathways are activated
by MTX in T cells and FLSs to inhibit NF-kappaB activation.
PMID- 25118319
TI - Standards for the management of sexually transmitted infections--2014.
PMID- 25118318
TI - The first gamma-H2AX biodosimetry intercomparison exercise of the developing
European biodosimetry network RENEB.
AB - In the event of a mass casualty radiation incident, the gamma-H2AX foci assay
could be a useful tool to estimate radiation doses received by individuals. The
rapid processing time of blood samples of just a few hours and the potential for
batch processing, enabling high throughput, make the assay ideal for early triage
categorisation to separate the 'worried well' from the low and critically exposed
by quantifying radiation-induced foci in peripheral blood lymphocytes. Within the
RENEB framework, 8 European laboratories have taken part in the first European
gamma-H2AX biodosimetry exercise, which consisted of a telescoring comparison of
200 circulated foci images taken from 8 samples, and a comparison of 10 fresh
blood lymphocyte samples that were shipped overnight to participating labs 4 or
24 h post-exposure. Despite large variations between laboratories in the dose
response relationship for foci induction, the obtained results indicate that the
network should be able to use the gamma-H2AX assay for rapidly identifying the
most severely exposed individuals within a cohort who could then be prioritised
for accurate chromosome dosimetry.
PMID- 25118320
TI - The utility of cerebrospinal fluid analysis in the investigation and treatment of
neurosyphilis.
PMID- 25118321
TI - Providing a genitourinary medicine colposcopy service.
PMID- 25118322
TI - Diagnostics within the clinic to test for gonorrhoea and chlamydia reduces the
time to treatment: a service evaluation.
PMID- 25118323
TI - Prevalence of and factors mediating HIV infection among sex workers in Lisbon,
Portugal: the 5-year experience of a community organisation.
PMID- 25118324
TI - Psychosocial and sexual healthcare needs in men selling sex in Glasgow: a
retrospective case note review.
PMID- 25118325
TI - Syphilis: a historical vignette.
PMID- 25118326
TI - Lipocalin 2 as a membrane-reorganizing agent.
AB - Lipocalins are a class of proteins that scavenge hydrophobic molecules in diverse
contexts, including the immune system, the nervous system, and cancer. A recent
study by Watanbe et al. identifies lipocalin 2 produced by the female mouse
reproductive tract as a sperm-capacitating agent that alters the membrane
properties of sperm in preparation for fertilization. The potential for
lipocalins to act as general modulators of plasma membrane bioactivity is
discussed.
PMID- 25118329
TI - The tyrosine kinase Lyn limits the cytokine responsiveness of plasma cells to
restrict their accumulation in mice.
AB - Maintenance of an appropriate number of plasma cells, long-lived antibody
producing cells that are derived from B cells, is essential for maintaining
immunological memory while limiting disease. Plasma cell survival relies on
extrinsic factors, the limited availability of which determines the size of the
plasma cell population. Mice deficient in the nonreceptor tyrosine kinase Lyn are
prone to an autoimmune disease that is characterized by inflammation and an
excess of plasma cells (plasmacytosis). We demonstrated that the plasmacytosis
was intrinsic to B cells and independent of inflammation. We also showed that Lyn
attenuated signaling by signal transducer and activator of transcription 3
(STAT3) and STAT5 in response to the cytokines interleukin-6 (IL-6) and IL-3,
respectively, in two previously uncharacterized plasma cell signaling pathways.
Thus, in the absence of Lyn, the survival of plasma cells was improved, which
enabled the plasma cells to become established in excess numbers in niches in
vivo. These data identify Lyn as a key regulator of survival signaling in plasma
cells, limiting plasma cell accumulation and autoimmune disease susceptibility.
PMID- 25118331
TI - Commentary on: the oncoplastic reduction approach to breast conservation therapy:
benefits for margin control.
PMID- 25118328
TI - Type IV collagen is an activating ligand for the adhesion G protein-coupled
receptor GPR126.
AB - GPR126 is an orphan heterotrimeric guanine nucleotide-binding protein (G protein)
coupled receptor (GPCR) that is essential for the development of diverse organs.
We found that type IV collagen, a major constituent of the basement membrane,
binds to Gpr126 and activates its signaling function. Type IV collagen stimulated
the production of cyclic adenosine monophosphate in rodent Schwann cells, which
require Gpr126 activity to differentiate, and in human embryonic kidney (HEK) 293
cells expressing exogenous Gpr126. Type IV collagen specifically bound to the
extracellular amino-terminal region of Gpr126 containing the CUB (complement,
Uegf, Bmp1) and pentraxin domains. Gpr126 derivatives lacking the entire amino
terminal region were constitutively active, suggesting that this region inhibits
signaling and that ligand binding relieves this inhibition to stimulate receptor
activity. A new zebrafish mutation that truncates Gpr126 after the CUB and
pentraxin domains disrupted development of peripheral nerves and the inner ear.
Thus, our findings identify type IV collagen as an activating ligand for GPR126,
define its mechanism of activation, and highlight a previously unrecognized
signaling function of type IV collagen in basement membranes.
PMID- 25118330
TI - Low-dose CT for patients with clinically suspected acute appendicitis: optimal
strength of sinogram affirmed iterative reconstruction for image quality and
diagnostic performance.
AB - BACKGROUND: As there is increased concern over the radiation exposure
particularly in adolescents and young adults, computed tomography (CT) dose
reduction is needed in the diagnosis of acute appendicitis. PURPOSE: To evaluate
the optimal strength of sinogram affirmed iterative reconstruction (SAFIRE) to
obtain the best image quality on a 30-mAs applied low-dose CT (LDCT 30mAs) and to
compare the diagnostic performances of the LDCT 30mAs with different SAFIRE
strengths with that of the 100-mAs applied LDCT (LDCT 100mAs) for the diagnosis
of acute appendicitis. MATERIAL AND METHODS: A total of 102 consecutive patients
(47 men, 55 women; mean age, 41.2 years; range, 15-82 years) with right lower
quadrant pain underwent abdominal-pelvic CT, consisting of arterial phase LDCT
100mAs and portal venous phase LDCT30mAs under a fixed 120 kV. LDCT 30mAs images
were reconstructed separately with five strength levels (S1-S5). Two blinded
radiologists recorded scores for the subjective image quality of the LDCT 30mAs
dataset (S0-S5) and confidence scores for the diagnosis of acute appendicitis on
each dataset and LDCT 100mAs. CT image noise was measured for each set. RESULTS:
The study population consisted of 58 patients with confirmed appendicitis and 44
without appendicitis. There was no significant difference in diagnostic
performance between LDCT 100mAs and LDCT 30mAs with any strength for both readers
(AUC for reader 1, LDCT 30mAs with S0-S5 = 0.97, LDCT 100mAs = 0.93, P = 0.0936;
for reader 2, LDCT 30mAs with S0-S5 = 0.96, LDCT 100mAs = 0.97, P = 0.128). The
measured noise decreased as the strength increased from S0 to S5 (mean, 20.8 >
17.7 > 15.6 > 13.5 > 11.5 > 9.5, P < 0.0001). However, overall subjective image
quality on S3 was better than the other strengths for both readers (S0 < S1 < S2
< S3 > S4 > S5, P < 0.0001). CONCLUSION: Although measured noise declined as
SAFIRE strength increased, S3 seems optimal for the best subjective image quality
on LDCT 30mAs. The diagnostic performance of LDCT 30mAs with any strength is
comparable to that of LDCT 100mAs for the diagnosis of acute appendicitis.
PMID- 25118327
TI - Targeting aPKC disables oncogenic signaling by both the EGFR and the
proinflammatory cytokine TNFalpha in glioblastoma.
AB - Grade IV glioblastoma is characterized by increased kinase activity of epidermal
growth factor receptor (EGFR); however, EGFR kinase inhibitors have failed to
improve survival in individuals with this cancer because resistance to these
drugs often develops. We showed that tumor necrosis factor-alpha (TNFalpha)
produced in the glioblastoma microenvironment activated atypical protein kinase C
(aPKC), thereby producing resistance to EGFR kinase inhibitors. Additionally, we
identified that aPKC was required both for paracrine TNFalpha-dependent
activation of the transcription factor nuclear factor kappaB (NF-kappaB) and for
tumor cell-intrinsic receptor tyrosine kinase signaling. Targeting aPKC decreased
tumor growth in mouse models of glioblastoma, including models of EGFR kinase
inhibitor-resistant glioblastoma. Furthermore, aPKC abundance and activity were
increased in human glioblastoma tumor cells, and high aPKC abundance correlated
with poor prognosis. Thus, targeting aPKC might provide an improved molecular
approach for glioblastoma therapy.
PMID- 25118332
TI - Insulin treatment prevents the increase in D-serine in hippocampal CA1 area of
diabetic rats.
AB - PURPOSE: Diabetes is a high risk factor for dementia. Employing a diabetic rat
model, the present study was designed to determine whether the content of D
serine (D-Ser) in hippocampus is associated with the impairment of spatial
learning and memory ability. METHODS: Diabetes was induced by a single
intravenous injection of streptozotocin (STZ). The insulin treatment began 3 days
after STZ injection. RESULTS: We found that both water maze learning and
hippocampal CA1 long-term potentiation (LTP) were impaired in diabetic rats. The
contents of glutamate, D-Ser, and serine racemase in the hippocampus of diabetic
rats were significantly higher than those in the control group. Insulin treatment
prevented the STZ-induced impairment in water maze learning and hippocampal CA1
LTP in diabetic rats and also maintained the contents of glutamate, D-Ser, and
serine racemase at the normal range in hippocampus. CONCLUSIONS: These results
suggest that insulin treatment has a potent protection effect on CA1-LTP, spatial
learning and memory ability of the diabetic rats in vivo. Furthermore, insulin
may take effect by inhibiting the overactivation of N-methyl-d-aspartate
receptors, which play a critical role in neurotoxicity.
PMID- 25118333
TI - Evaluation of a pet-assisted living intervention for improving functional status
in assisted living residents with mild to moderate cognitive impairment: a pilot
study.
AB - BACKGROUND: In older adults with cognitive impairment (CI), decreased functional
status and increased behavioral symptoms require relocation from assisted living
(AL) to nursing homes. Studies support positive effects of pets on
health/function. PURPOSE: Evaluate the effectiveness of the Pet AL (PAL)
intervention to support physical, behavioral, and emotional function in AL
residents with CI. METHODS: Cognitively impaired AL residents randomized to 60-90
minute sessions [PAL (n = 22) or reminiscing (n = 18)] twice/week for 12 weeks.
PAL interventionist encourages residents to perform skills with the visiting dog;
reminiscing interventionist encourages residents to reminisce. Monthly assessment
of physical (energy expenditure, activities of daily living), emotional
(depression, apathy), and behavioral (agitation) function. RESULTS: In linear
mixed models, physical activity depressive symptoms improved more with PAL.
CONCLUSION: Evidence supports that the PAL program helps preserve/enhance
function of AL residents with CI. Additional study is required to evaluate the
duration and predictors of effectiveness of the PAL intervention.
PMID- 25118335
TI - Oil binding capacities of triacylglycerol crystalline nanoplatelets: nanoscale
models of tristearin solids in liquid triolein.
AB - Polycrystalline particles composed of triacylglycerol (TAG) molecules, and their
networks, in anhydrous TAG oils find extensive use as edible oils in the food
industry. Although modelling studies of TAG systems, have been carried out, none
have attempted to address a problem of central concern to food science and
technology: the "oil binding capacity" of a system of such edible oils.
Crystalline nanoparticles (CNPs) have recently been identified as the fundamental
components of solid fats in oils. Oil binding capacity is an important concept
regarding the ability of fats particles to retain oil, and the ability of these
CNPs to bind oil is important in designing healthy foods. We have carried out
atomic scale molecular dynamics computer simulations to understand the behavior
of a triacylglycerol oil (triolein) in nanoscale confinements between tristearin
CNPs. We define a nanoscale oil binding capacity function by utilizing the
average oil number density, , between two CNPs as a function of their
separation, d. We modelled pure tristearin CNPs as well as tristearin CNPs in
which the surfaces are covered with an interface comprising soft permanent
coatings. Their surfaces are "hard" and "soft" respectively. We found that for a
pair of hard-surface tristearin CNPs a distance d apart, (i) triolein exhibits
number density, and therefore density, oscillations as a function of d, and (ii)
the average number density between two such CNPs decreases as d decreases, viz.
the oil binding capacity is lowered. When a soft layer of oil covers the CNP
surfaces, we found that the oscillations are smeared out and that the average
number density between the two CNPs remained approximately constant as d
decreased indicating a high oil binding capacity. Our results might have
identified important nanoscale aspects to aid in healthy food design.
PMID- 25118334
TI - Strengthening the dementia care triad: identifying knowledge gaps and linking to
resources.
AB - This article describes a project to identify the needs of family caregivers and
health care providers caring for persons with dementia. Participants included 128
caregivers, who completed a survey, and 27 health care providers, who
participated in a focus group and completed a survey. Caregivers reported their
primary source of information about the disease was the doctor; however, the
majority also reported they were primarily informed of medications and not about
needed resources. Health care providers identified limited time with patients and
families, and lack of awareness of community services, as their main challenges.
Recommendations include strengthening the partnership between physicians,
patients, and caregivers (the dementia care triad) through additional support and
training for physicians and caregivers, increasing awareness of the Alzheimer's
Association, and utilization of technology for families and professionals to
track the needs of persons with dementia.
PMID- 25118336
TI - Direct analysis of quaternary alkaloids by in situ reactive desorption corona
beam ionization MS.
AB - The direct detection of quaternary alkaloids by atmospheric pressure chemical
ionization (APCI)-base ambient MS is difficult because of their poor volatility.
In this study, a reactive protocol was developed for the in situ determination of
quaternary alkaloids using desorption corona beam ionization (DCBI) mass
spectrometry (MS). The model compounds of 8 quaternary alkaloids including
sanguinarine, chelerythrine, cyclanoline, nitidine, coptisine, jatrorrhizine,
berberine, palmatine and 2 tertiary alkaloids including protopine and
allocryptopine were investigated in different states such as on a
polytetrafluoroethylene (PTFE) plate, in raw herbal materials, and in silica gel.
After various reactive reagents were studied, the mixture of saturated aqueous
NaOH solution and CH3OH solvent (3 : 7, v/v) was selected as the optimized
reactive reagent for the reactive DCBI-MS detection. All the target molecules can
be detected with high sensitivity. On a PTFE plate the limits of detection were
0.0795, 0.1060, 0.4860, 0.9665, 0.8879, 0.3987, 0.5557, 0.4591, 0.0889, and
0.1929 mg L(-1) for sanguinarine, chelerythrine, cyclanoline, nitidine,
coptisine, jatrorrhizine, berberine, palmatine, protopine, and allocryptopine,
respectively. The reactive protocol was also applied to the direct detection of
raw herbal materials and thin layer chromatography successfully.
PMID- 25118338
TI - Near infrared hyperspectral imaging for forensic analysis of document forgery.
AB - Hyperspectral images in the near infrared range (HSI-NIR) were evaluated as a
nondestructive method to detect fraud in documents. Three different types of
typical forgeries were simulated by (a) obliterating text, (b) adding text and
(c) approaching the crossing lines problem. The simulated samples were imaged in
the range of 928-2524 nm with spectral and spatial resolutions of 6.3 nm and 10
MUm, respectively. After data pre-processing, different chemometric techniques
were evaluated for each type of forgery. Principal component analysis (PCA) was
performed to elucidate the first two types of adulteration, (a) and (b).
Moreover, Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) was
used in an attempt to improve the results of the type (a) obliteration and type
(b) adding text problems. Finally, MCR-ALS and Partial Least Squares-Discriminant
Analysis (PLS-DA), employed as a variable selection tool, were used to study the
type (c) forgeries, i.e. crossing lines problem. Type (a) forgeries (obliterating
text) were successfully identified in 43% of the samples using both the
chemometric methods (PCA and MCR-ALS). Type (b) forgeries (adding text) were
successfully identified in 82% of the samples using both the methods (PCA and MCR
ALS). Finally, type (c) forgeries (crossing lines) were successfully identified
in 85% of the samples. The results demonstrate the potential of HSI-NIR
associated with chemometric tools to support document forgery identification.
PMID- 25118337
TI - Highly sensitive and selective detection of Pb2+ ions using a novel and simple
DNAzyme-based quartz crystal microbalance with dissipation biosensor.
AB - A novel, label-free DNAzyme-based quartz crystal microbalance with dissipation
monitoring (QCM-D) biosensor was developed for the highly sensitive and specific
detection of Pb(2+) ions. To enhance the performance of the sensor,
oligonucleotide-functionalized gold nanoparticles were used for both frequency
and dissipation amplification. This sensor was developed by immobilizing Pb(2+)
specific DNAzymes onto the QCM-D sensor surface and allowing them to hybridize
with substrate-functionalized AuNPs. The DNAzyme catalyzed the cleavage of the
substrate in the presence of Pb(2+) ions, causing the cleaved substrate
functionalized AuNPs to be removed from the sensor surface. Thus, Pb(2+) ions can
be determined on-line by monitoring the change in frequency and dissipation
signals. The results revealed that the sensor showed a sensitive response to
Pb(2+) ions with detection limits of 14 nM and 20 nM for frequency and
dissipation, respectively. This QCM-D biosensor also exhibited excellent
selectivity toward Pb(2+) ions in the presence of other divalent metal ions. In
addition, the approach was able to detect Pb(2+) in tap water, demonstrating its
great potential for monitoring drinking water quality. The proposed sensor system
described here represents a new class of lead ion sensor. Its simple detection
strategy makes it feasible for 'pollution-free' detection; thus, the approach
could have applications in on-line water quality monitoring.
PMID- 25118339
TI - Nanopipette delivery: influence of surface charge.
AB - In this report, transport through a nanopipette is studied and the interplay
between current rectification and ion delivery for small pipettes is examined.
First, surface charge dependence of concentration polarization effects in a
quartz nanopipette was investigated. Electrical characterization was performed
through current-potential (I-V) measurements. In addition, fluorescein (an
anionic fluorescent probe) was utilized to optically map ion enrichment and ion
depletion in the nanopipette tip. Bare nanopipettes and polyethylenimine (PEI)
modified nanopipettes were examined. Results confirm that concentration
polarization is a surface charge dependent phenomenon and delivery can be
controlled through modification of surface charge. The relationship between
concentration polarization effects and voltage-driven delivery of charged
electroactive species was investigated with a carbon ring/nanopore electrode
fabricated from pyrolyzed parylene C (PPC). Factors such as surface charge
polarity of the nanopipette, electrolyte pH, and electrolyte concentration were
investigated. Results indicate that with modification of surface charge,
additional control over delivery of charged species can be achieved.
PMID- 25118340
TI - Dual amplification of single nucleotide polymorphism detection using graphene
oxide and nanoporous gold electrode platform.
AB - In the present manuscript, a strategy to prompt the sensitivity of a biosensor
based on the dual amplification of signal by applying a nanoporous gold electrode
(NPGE) as a support platform and soluble graphene oxide (GO) as an indicator has
been developed. By increasing the surface area of the biosensing platform and
because of unique GO/ss-DNA interactions, the sensitivity for the detection of
SNPs is enhanced. In the presence of SNPs, because of less effective
hybridization of mutant targets compared to complementary targets, further GO
could adsorb on mutant targets-modified NPGE viapi-pi interactions, causing a
large increase in the charge transfer resistance (Rct) of the electrode. This
protocol provides a cost-effective and fast method for the discrimination of
different SNPs. Furthermore, this biosensor can detect thermodynamically stable
SNP (G-T mismatches) in the range of 15-1600 pM. The present strategy is a label
free and sensitive protocol and does not require sophisticated fabrication.
PMID- 25118341
TI - Electrolytic valving isolation of cell co-culture microenvironment with
controlled cell pairing ratios.
AB - Cancer-stromal interaction is a critical process in tumorigenesis. Conventional
dish-based co-culture assays simply mix two cell types in the same dish; thus,
they are deficient in controlling cell locations and precisely tracking single
cell behavior from heterogeneous cell populations. Microfluidic technology can
provide a good spatial-temporal control of microenvironments, but the control has
been typically realized by using external pumps, making long-term cultures
cumbersome and bulky. In this work, we have presented a cell-cell interaction
microfluidic platform that can accurately control the co-culture microenvironment
by using a novel electrolytic cell isolation scheme without using any valves or
pneumatic pumps. The proposed microfluidic platform can also precisely control
the number of interacting cells and pairing ratios to emulate cancer niches. More
than 80% of the chambers captured the desired number of cells. The duration of
cell isolation can be adjusted by electrolytic bubble generation and removal. We
have verified that the electrolytic process has a negligible effect on cell
viability and proliferation in our platform. To the best of our knowledge, this
work is the first attempt to incorporate electrolytic bubble generation as a cell
isolation method in microfluidics. For proof of feasibility, we have performed
cell-cell interaction assays between prostate cancer (PC3) cells and myoblast
(C2C12) cells. The preliminary results demonstrated the potential of using
electrolysis for micro-environmental control during cell culture. Also, the ratio
controlled cell-cell interaction assays were successfully performed which showed
that the cell pairing ratios of PC3 to C2C12 affected the proliferation rate of
myoblast cells due to increased secretion of growth factors from prostate cancer
cells.
PMID- 25118343
TI - Development and delivery of a high-quality European Cardiovascular Magnetic
Resonance Examination.
PMID- 25118342
TI - Authors' response.
PMID- 25118344
TI - The Glasgow Cardiovascular Research Centre of the British Heart Foundation.
PMID- 25118345
TI - Country of the month: Ireland 2014.
PMID- 25118346
TI - Automated external defibrillators should be mandatory on board all commercial
airliners.
PMID- 25118347
TI - Author's response.
PMID- 25118348
TI - High-dimensional cytometry. Preface.
PMID- 25118349
TI - Retracted: Synthesis and cytotoxic activity of 2-anilinopyridine-3-acrylamides as
tubulin polymerization inhibitors.
PMID- 25118350
TI - How to become a successful researcher: tips for early career researchers.
PMID- 25118351
TI - Elucidation of sevadicin, a novel non-ribosomal peptide secondary metabolite
produced by the honey bee pathogenic bacterium Paenibacillus larvae.
AB - American foulbrood (AFB) caused by the bee pathogenic bacterium Paenibacillus
larvae is the most devastating bacterial disease of honey bees worldwide. From
AFB-dead larvae, pure cultures of P. larvae can normally be cultivated indicating
that P. larvae is able to defend its niche against all other bacteria present.
Recently, comparative genome analysis within the species P. larvae suggested the
presence of gene clusters coding for multi-enzyme complexes, such as non
ribosomal peptide synthetases (NRPSs). The products of these enzyme complexes are
known to have a wide range of biological activities including antibacterial
activities. We here present our results on antibacterial activity exhibited by
vegetative P. larvae and the identification and analysis of a novel
antibacterially active P. larvae tripeptide (called sevadicin; Sev) produced by a
NRPS encoded by a gene cluster found in the genome of P. larvae. Identification
of Sev was ultimately achieved by comparing the secretome of wild-type P. larvae
with knockout mutants of P. larvae lacking production of Sev. Subsequent mass
spectrometric studies, enantiomer analytics and chemical synthesis revealed the
sequence and configuration of the tripeptide, D-Phe-D-ALa-Trp, which was shown to
have antibacterial activity. The relevance of our findings is discussed in
respect to host-pathogen interactions.
PMID- 25118352
TI - Cyclic-di-GMP levels affect Pseudomonas aeruginosa fitness in the presence of
imipenem.
AB - A large number of genes coding for enzymes predicted to synthesize and degrade 3'
5-cyclic diguanylic acid (c-di-GMP) is found in most bacterial genomes and this
dinucleotide emerged as an intracellular signal-controlling bacterial behaviour.
An association between high levels of c-di-GMP and antibiotic resistance may be
expected because c-di-GMP regulates biofilm formation and this mode of growth
leads to enhanced antibiotic resistance. However, a clear understanding of this
correlation has not been established. We found that increased levels of c-di-GMP
in Pseudomonas aeruginosa improve fitness in the presence of imipenem, even when
grown as planktonic cells. P. aeruginosa post-transcriptionally regulates the
amounts of five porins in response to c-di-GMP, including OprD, responsible for
imipenem uptake. Cells with low c-di-GMP levels are consequently more sensitive
to this antibiotic. Main efflux pumps or beta-lactamase genes did not show
altered mRNA levels in P. aeruginosa strains with modified different c-di-GMP
concentrations. Together, our findings show that c-di-GMP levels modulate fitness
of planktonic cultures in the presence of imipenem.
PMID- 25118353
TI - Efficacy of scorpion antivenom in children--author's reply.
PMID- 25118354
TI - Experience of nutrition rehabilitation centers in management of SAM--author's
reply.
PMID- 25118355
TI - Cord blood TSH for screening of hypothyroidism: is it justified--author's reply.
PMID- 25118356
TI - Good night, sleep tight. Get better sleep without taking a pill.
PMID- 25118357
TI - The best options for different types of neck pain. Prompt treatment can help
prevent long-term problems.
PMID- 25118358
TI - Finding relief for recalcitrant bursitis pain.
PMID- 25118359
TI - Improving range of motion in arthritic joints.
PMID- 25118360
TI - What to do about back spasms.
PMID- 25118361
TI - Is it safe to use nonprescription topical medication for my joint and muscle
pain?
PMID- 25118362
TI - I have knee osteoarthritis (OA), and a friend recommended shock-absorbing insoles
to reduce the pain. Are they really effective?
PMID- 25118363
TI - Back pain and bedtime--getting the right support.
PMID- 25118364
TI - Lowering your breast cancer risk. A daily pill can hold the key to prevention
for some women.
PMID- 25118365
TI - Pain of a higher order: cluster headaches.
PMID- 25118366
TI - [Clinical oncology and the status of oncosurgery].
PMID- 25118368
TI - Medical devices; gastroenterology-urology devices; classification of the
implantable transprostatic tissue retractor system. Final order.
AB - The Food and Drug Administration (FDA) is classifying the implantable
transprostatic tissue retractor system into class II (special controls). The
special controls that will apply to the device are identified in this order and
will be part of the codified language. The Agency is classifying the device into
class II (special controls) in order to provide a reasonable assurance of safety
and effectiveness of the device.
PMID- 25118367
TI - Gastroenterology-urology devices; reclassification of implanted blood access
devices. Final rule.
AB - The Food and Drug Administration (FDA) is issuing a final order to reclassify
implanted blood access devices, a preamendments class III device, into class II
(special controls) based on new information and subject to premarket notification
and to further clarify the identification.
PMID- 25118369
TI - Final priority; National Institute on Disability and Rehabilitation Research-
Disability and Rehabilitation Research Projects and Centers Program. Final
priority.
AB - The Assistant Secretary for Special Education and Rehabilitative Services
announces a priority under the Disability and Rehabilitation Research Projects
and Centers Program administered by the National Institute on Disability and
Rehabilitation Research (NIDRR). Specifically, we announce a priority for a
Disability and Rehabilitation Research Project (DRRP) on Improving Methods of
Evaluating Return on Investment (ROI) for the State Vocational Rehabilitation
Services Program (VR Program). The Assistant Secretary may use this priority for
competitions in fiscal year (FY) 2014 and later years. We take this action to
focus research attention on an area of national need. We intend for the priority
to contribute to improved employment outcomes for individuals with disabilities.
PMID- 25118370
TI - Final priority; National Institute on Disability and Rehabilitation Research-
Rehabilitation Research and Training Centers. Final priority.
AB - The Assistant Secretary for Special Education and Rehabilitative Services
announces a priority for the Rehabilitation Research and Training Center (RRTC)
Program administered by the National Institute on Disability and Rehabilitation
Research (NIDRR). Specifically, we announce a priority for an RRTC on Vocational
Rehabilitation Practices for Youth and Young Adults. The Assistant Secretary may
use this priority for competitions in fiscal year (FY) 2014 and later years. We
take this action to focus research attention on an area of national need. We
intend for this priority to contribute to improved outcomes for youth and young
adults with disabilities in the State Vocational Rehabilitation Services program.
PMID- 25118371
TI - Final priority; National Institute on Disability and Rehabilitation Research-
Research Fellowships Program (also known as the Mary E. Switzer Research
Fellowships). Final priority.
AB - The Assistant Secretary for Special Education and Rehabilitative Services
announces a priority for the Research Fellowships Program administered by the
National Institute on Disability and Rehabilitation Research (NIDRR).
Specifically, this notice announces a priority for a Distinguished Residential
Disability and Rehabilitation Policy Fellowship. We take this action to focus
attention on an area of national need. We intend the priority to build research
capacity by providing support to highly qualified, experienced researchers,
including those who are individuals with disabilities, to conduct policy research
in the areas of disability and rehabilitation.
PMID- 25118372
TI - Rules regarding the health insurance premium tax credit. Final and temporary
regulations.
AB - This document contains final and temporary regulations relating to the health
insurance premium tax credit enacted by the Patient Protection and Affordable
Care Act and the Health Care and Education Reconciliation Act of 2010, as amended
by the Medicare and Medicaid Extenders Act of 2010, the Comprehensive 1099
Taxpayer Protection and Repayment of Exchange Subsidy Overpayments Act of 2011,
and the Department of Defense and Full-Year Continuing Appropriations Act of 2011
and the 3% Withholding Repeal and Job Creation Act. These regulations affect
individuals who enroll in qualified health plans through Affordable Insurance
Exchanges (Exchanges) and claim the premium tax credit, and Exchanges that make
qualified health plans available to individuals. The text of the temporary
regulations in this document also serves as the text of proposed regulations set
forth in a notice of proposed rulemaking (REG-104579-13) on this subject in the
Proposed Rules section in this issue of the Federal Register.
PMID- 25118373
TI - Branded prescription drug fee. Final regulations, temporary regulations, and
removal of temporary regulations.
AB - This document contains final regulations that provide guidance on the annual fee
imposed on covered entities engaged in the business of manufacturing or importing
branded prescription drugs. This fee was enacted by section 9008 of the Patient
Protection and Affordable Care Act, as amended by section 1404 of the Health Care
and Education Reconciliation Act of 2010. This document also withdraws the
Branded Prescription Drug Fee temporary regulations and contains new temporary
regulations regarding the definition of controlled group that apply beginning on
January 1, 2015. The final regulations and the new temporary regulations affect
persons engaged in the business of manufacturing or importing certain branded
prescription drugs. The text of the temporary regulations in this document also
serves as the text of proposed regulations set forth in a notice of proposed
rulemaking (REG-123286-14) on this subject in the Proposed Rules section in this
issue of the Federal Register.
PMID- 25118374
TI - [Study on adjuvant effect of oral recombinant subunit vaccine formulated with
chitosan against human enterovirus 71].
AB - To evaluate the adjuvant effect of recombinant enterovirus 71 (EV71) subunit
vaccine formulated with chitosan, rabbits were orally immunized with recombinant
VP1 (rVP1) or rVP1 mixed with chitosan adjuvant. Levels of virus-specific IgG and
IgA antibodies in sera, mucosal wash buffer (intestine, nasal cavity, and lung),
and feces were determined by indirect enzyme-linked immunosorbent assay (ELISA).
The titers of neutralizing antibodies against EV71 were determined using
cytopathic effect-based neutralizing assay, and levels of cytokines (IFN-gamma
and IL-4) secreted from in vitro-cultured rabbit splenic lymphocytes under
antigen stimulation were also determined by ELISA. Results showed that
immunization with rVP1 alone could only induce low levels of serum IgG and
mucosal IgA, while rVP1 combined with chitosan adjuvant were able to induce
significantly higher levels of antibodies, rVP1 can only induce neutralizing
antibodies when used in combination with chitosan. Levels of IFN-gamma and IL-4
in the group immunized with rVP1 plus chitosan were significantly higher than
those in the group immunized with rVP1 only or those in the control groups. Our
study lays the foundation for development of oral VP1 vaccine against EV71
infection.
PMID- 25118376
TI - [Severe fever with thrombocytopenia syndrome virus nucleoprotein specifically
binds to 60kD SSA/Ro protein in host cells].
AB - This study aims to investigate whether the nucleoprotein (NP) of severe fever
with thrombocytopenia syndrome virus (SFTSV) can impact the cellular immunity of
host cells. Gene segments that encode the NP and non-structural protein (NSs) of
SFTSV were inserted into eukaryotic expression vector VR1012. Host proteins that
interact with NP and affect immunity were identified with co-immunoprecipitation
(IP), SDS-PAGE, mass spectrometry (MS), and Western blot. Co-localization of NP
and the identified host proteins was confirmed by confocal microscopy. A 60kD
SSA/Ro, a protein related to immunity, interacted with NP, as found by IP and MS.
Confocal microscopy showed that NP and SSA/Ro were co-localized in cytoplasm.
These results indicated that SFTSV NP may specifically bind to 60kD SSA/Ro and
cause a series of immune responses and clinical symptoms.
PMID- 25118375
TI - [Immunoprotective effect of inactivated coxsackievirus A16 vaccine in mice].
AB - This study aims to construct inactivated coxsackievirus A16 (CVA16) vaccine and
to investigate its protective effect in ICR mice. A clinical isolate of CVA16,
521-01T, was cultured in VERO cells, inactivated by formaldehyde, and purified by
ultracentrifugation for vaccine preparation. Purity and other characteristics of
the vaccine were determined by SDS-PAGE and Western blot. Female ICR mice were
subcutaneously inoculated with inactivated CVA16 or Al(OH)3-absorbed CVA16,
followed by booster immunization at the end of 2 and 4 weeks. CVA16-specific IgG
titers in serum were determined by ELISA, and titers of neutralizing antibodies
were determined by viral neutralization assay. The immunity of T lymphocytes was
evaluated by IFN-gamma ELISPOT assay. The protective effect was evaluated by
challenging the neonatal offspring (< 48 hours) of vaccinated female mice with 1
000 LD50 of CVA16 521-01T. The mortality rates of different groups were compared.
The results showed that Al(OH)3 +CVA16 could induce high titers of specific IgG
antibodies in ICR mice. After being boosted two times, the serum IgG antibody
titer could reach up to 1 : 1 x 10(5) (P = 0.000), and neutralizing antibody
titer was higher than 1 : 256. Additionally, more spot forming cells were induced
in the immunized groups than in the negative controls. The maternal antibodies
showed protective effect in 100% of the neonatal mice challenged with 1 000 LD50
of CVA16 521-01T. The inactivated CVA16 vaccine has ideal immunogenicity and
immunoprotective effect. This research lays a foundation for the development and
evaluation of CVA16 vaccines.
PMID- 25118377
TI - [Virological impact of stalk region of neuraminidase in influenza A/Anhui/1/05
(H5N1) and A/Ohio/07/2009 (H1N1) viruses].
AB - This study aims to investigate the virological impact of the stalk region and
cysteine (C) in neuraminidase (NA) of influenza A/Anhui/1/05 (H5N1) and
A/Ohio/07/2009 (H1N1) viruses. The NA of A/ Anhui/1/05 (H5N1), defined as AH N1,
lacked 20 amino acids (including C, defined as s20) as compared with NA of
A/Ohio/07/2009 (H1N1) (defined as 09N1). We deleted s20 of 09N1 to construct 09N1
s20, and inserted s20 into AH N1 to construct AH N1+s20. To investigate the
impact of C on the biological function of NA, we deleted C in 09N1 to construct
09N1-C and inserted C into AH N1 to construct AH N1-C. The pseudo-type viral
particle (pp) system was used to evaluate the impact of these mutants on
virology. The combination of 09N1-C and 09H1 (defined as 09H1::09N1-C) showed an
infectivity 8 times that of the wild type 09H1::09N1, while the infectivity of
the combination of AH N1+C and AH H5 (defined as AH H5::AH N1+C) was much lower
than that of the wild type AH H5::AH N1. The infectivity of the combination of
09N1-s20 and 09H1 (defined as 09H1::09N1-s20) was 4 times that of the wild type
09H1::09N1; the infectivity of the combination of AH N1+s20 and AH H5 (defined as
AH H5:: AH N1+s20) was 1/7 that of the wild type AH H5::AH N1. The co-existence
of 09N1-C and AH H5 displayed 6 times the infectivity of AH H5::09N1, while the
infectivity of 09H1::AH N1+C was very low. Multimer analysis showed that in the
wild type 09N1, the forms of NA were dimer >> tetramer > monomer; the major
component of NA in 09N1-C was monomer; in 09N1-s20, the forms of NA were monomer
>> dimer. AH N1 was mainly composed of monomer; in AH N1+s20, the forms of NA
were dimer >> monomer > tetramer; in AH N1+C, the forms of NA were dimer >>
tetramer. Deletion of C or s20 from 09N1 did not change the expression of NA. The
study suggested that deletion of C from the stalk region of NA in A/Ohio/07/2009
(H1N1) increases infectivity. Insertion of C into NA's stalk region of A/
Anhui/1/05 (H5N1) significantly decreases infectivity. Cysteine deletion in the
stalk region is important for the infectivity of A/Anhui/1/05 (H5N1) and
A/Ohio/07/2009 (H1N1). It may interfere with the infectivity via changes in NA
polymerization.
PMID- 25118378
TI - [Epidemiology of hand, foot, and mouth disease and genetic characterization of
enterovirus A71: a survey from 2007 to 2012 in Linyi of Shandong Province,
China].
AB - To investigate the epidemiology of hand, foot, and mouth disease (HFMD) and the
genetic characteristics of enterovirus A71 (EV-A71) in Linyi of Shandong
Province, China during 2007-2012. The number of reported HFMD cases were obtained
from the National Notifiable Disease Reporting System (NNDRS) were analyzed by
descriptive epidemiology method; the VP1 region of EV-A71 isolated from HFMD
patients in Linyi was amplified and sequenced. Finally, the genetic variability
and phylogenecity of VP1 sequences of EV-A71 were analyzed by MEGA 5.0. The
results showed that HFMD incidence was reported in each year from 2007 to 2012 in
Linyi, and the highest incidence and mortality were reported in 2009, when there
were total 14697 cases and 9 of death. The reported incidence was 140.28/100000,
and the mortality was 0.086/100000. The peak incidence usually occurred between
April and July, and the summit occurred in May. Scattered children accounted for
77.37%-92.00% of all cases. The peak age was 2.5 years during 2007-2009 and 1.5
years during 2010-2012. A total of 1365 laboratory-confirmed HFMD cases were
reported in the 6 consecutive years, accounting for 2.98% of the gross number.
Among these reports, the ratio of EV-A71 was 44.18%, and the ratio of
coxsackievirus A16 (CVA16) was 46.59%. All EV-A71 strains isolated in Linyi
during 2007-2012 belonged to the C4a evolutionary branch of C4 genotype. In
conclusion, HFMD outbreaks occurred every year in Linyi during 2007-2012.
Incidence varied significantly among different counties. The peak incidence in
each year lasted from April to July. Most of the patients were children under 3
years of age, and scattered children took the highest proportion. Co-circulation
of EV-A71 and CVA16 was the major cause of HFMD in each year. Since the first
report of HFMD prevalence caused by EV-A71 (C4a) in 2007, the virus has been
prevalent continuously in Linyi for 6 years.
PMID- 25118379
TI - [Study on the B cell linear epitopes of rabies virus CVS-11 nucleoprotein].
AB - To study the B cell linear epitopes of rabies virus CVS-11 nucleoprotein,
peptides were synthesized according to the amino acid sequences of B cell linear
epitopes. Linear epitopes predicted by bioinformatics analysis were evaluated
with immunological techniques. Indirect enzyme-linked immunosorbent assay showed
that titers of antibodies to peptides (355-369 and 385-400 residues of rabies
virus CVS-11 nucleoprotein) were above 1:12 800 in mouse sera. The antibodies
recognized denatured rabies virus CVS-11 nucleoprotein in Western blot analysis.
Purified anti-peptide antibodies recognized natural rabies virus CVS-11
nucleoprotein in BHK-21 cells in indirect fluorescent antibody test. The 355-369
and 385-400 residues of rabies virus CVS-11 nucleoprotein were validated as B
cell linear epitopes.
PMID- 25118380
TI - [Genome amplification and sequence analysis of human bocavirus 2].
AB - To obtain the genome sequence of human bocavirus 2 (HBoV2), different regions of
HBoV2 genome were amplified through PCR in fecal specimens which had been
identified as single-positive for HBoV2 in 2010. A genome sequence of HBoV2
(HBoV2-NC, 5444 bp) was obtained after sequence assembly. The phylogenetic
analysis showed that HBoV2-NC had the closest evolutionary relationship with
HBoV2 Lanzhou strain. The predication of inverted terminal repeats of HBoV2-NC by
DINAMelt showed that inverted terminal repeats were contained in HBoV2-NC 5'
terminal, which had the typical stem-loop structure in other parvoviruses.
Finally, some flanking sequences of HBoV2-NC were amplified by linker-PCR.
PMID- 25118381
TI - [Genetic characteristics of influenza A/H3N2 virus neuraminidase gene: a survey
from 2010 to 2012 in Qinghai Province, China].
AB - This study aims to perform a survey of genetic variation in neuraminidase (NA)
gene of influenza A/H3N2 virus, as well as related resistance to NA inhibitors,
in Qinghai Province of China, 2010 to 2012. Strains of influenza A/H3N2 isolated
during an influenza survey from 2010 to 2012 in Qinghai were enrolled by random
sampling. Viral RNA was extracted and amplified by RT-PCR. Purified PCR products
were sequenced thereafter. Genetic analysis of nucleic acid and the derived amino
acid sequences was performed by MEGA 4.0. Phylogenetic trees were also
constructed. Strains isolated during 2010-2011 in this study clustered closely
with World Health Organization (WHO) 2010-2012 reference vaccine strain
A/Perth/16/2009 and 2008-2010 reference vaccine strain A/Brisbane/10/2007 on the
phylogenetic tree, while the 2012 isolates were located on another branch. In
analysis of derived amino acid sequences, the 2010 isolates mutated at K81T, the
2011 isolates mutated at I26V and D127N, while the 2012 isolates mutated at E41K,
P46A, I58V, T71N, L81P, D93G, D127N, D151N, and I307M. The D151N mutation added a
glycosylation site to the activity center of NA. No significant variation was
discovered in H3N2 NA gene of 2010-2011 isolates in Qinghai, China. Isolates of
2012 were found with significant mutation, which has the potential of inducing
minor resistance to NA inhibitors like zanamivir and oseltamivir.
PMID- 25118382
TI - [Research on construction of sheep lung adenomas virus pEGFP-C1/exJSRV-env and
induction of malignant transformation in NIH3T3].
AB - This study aims to construct a eukaryotic expression system for envelope gene of
Jaagsiekte sheep retrovirus, observes its localization in 293T cells, and
investigates the potential in inducing malignant transformation of NIH3T3 cells.
By RT-PCR, the full-length cDNA of envelope gene of Jaagsiekte sheep retrovirus
(exJSRV-env) was amplified from the extract of naturally infected sheep lung. The
clone of target gene was sub-cloned into eukaryotic expression system pEGFP-C1,
and validated by PCR, restriction endonuclease, and sequencing. Bioinformatic
analysis concerning biological function and cellular localiza tion of exJSRV-env
was also performed. The recombinant clone of exJSRV-env was transfected into 293T
cells and NIH3T3 cells by Lipofectamine LTX. The expression and celluar
localization in 293T cells were validated by confocal microscopy. Soft agar
colony formation assay was employed to test the anchorage-independent growth of
NIH3T3. DNA sequencing and restriction enzyme digestion with Kpn I and Hind III
indicated the correct construction of the recombinant plasmid, which was named
pEGFP-C1/exJSRV-env. Amino acid sequence alignment of exJSRV-env with reference
sequences found 85%-100% homogeneity. A YRNM motif was discovered at the
cytoplasmic tail of envelope gene, which is exclusively found in exogenous
viruses. Phylogenetic tree analysis showed that our clone of exJSRV-env clustered
closely with pathogenic exogenous Jaagsiekte sheep retroviruses. Fluorescence
microscopy indicated typical membrane localization of exJSRV-env protein. NIH3T3
cells transfected with exJSRV-env lost contact inhibition, and acquired colony
forming ability in soft agar. This study indicated that envelope protein of
Jaagsiekte sheep retrovirus can induce malignant transformation of mouse
fibroblast cell NIH3T3. Discoveries of this study provide a basis for further
structural and functional research on Jaagsiekte sheep retrovirus envelope
protein.
PMID- 25118383
TI - [Optimization of electroporation parameters for ctenopharyngodon idellus kidney
cells and transient expression of grass carp reovirus NS26 protein].
AB - In this study, pEGFP-N1 was chosen as the reporter plasmid and transferred into
Ctenopharyngodon idellus kidney (CIK) cells by electroporation, and the optimal
electroporation conditions were determined by testing the transfection efficiency
with different voltages, pulse times, plasmid amounts, and numbers of shocks. The
results showed that the maximum electroporation efficiency was achieved under the
following conditions in a 0.2 cm electroporation cuvette containing CIK cells
(1.5 x 10(7)/mL, 200 microl): electric voltage 200 V, pulse time 45 ms, plasmid
30 microg, and one electric shock. The total genomic RNA of grass carp reovirus
(GCRV) was extracted in this experiment and reversely transcribed into cDNA,
which was used to amplify the gene segment of GCRV non-structural protein NS26
using designed specific primers. The PCR product was recombined into pEGFP-N1
vector. The fusion protein EGFP-NS26 was successfully and efficiently expressed
in the CIK cells by electroporation, which was confirmed by both fluorescent
imaging and Western blot analysis. This experiment laid a foundation for further
functional studies of the non-structural protein NS26 of GCRV.
PMID- 25118384
TI - [Effects of bm47 deletion on viral replication and transcription of Bombyx mori
nucleopolyhedrovirus].
AB - Bombyx mori nucleopolyhedrovirus (BmNPV) bm47 gene is found in all sequenced
lepidopteran nucleopolyhedroviruses (NPVs). It is one of the core genes of NPVs.
However, the role of bm47 in the biological cycle of NPV remains unknown. In this
study, the Red recombination system was used to knock out bm47 from BmNPV to
construct bm47-ko-Bacmid in E. coli BW25113 system. Then bm47 gene was introduced
back to the viral genome using the Bac-to-Bac system to create the repair virus
bm47-re-Bacmid. TCID50 assay and real-time PCR (qPCR) were used to evaluate the
effects of bm47 deletion on viral DNA replication, gene transcription, and
protein expression. qPCR results showed that bm47 knock-out had no significant
effect on viral DNA replication. However, the qPCR results showed that bm47-ko
Bacmid significantly decreased the transcription levels of early gene lef-3, late
gene vp39, and very late gene p10 at 48 h and 72 h after viral transfection of
BmN cells (P < 0.05). This work will provide a foundation for further studies on
the biological function of BmNPV bm47 in viral replication and transcription.
PMID- 25118385
TI - [Characterization of Marburg virus morphology].
AB - Ebola virus (EBOV) and Marburg virus (MARV) belong to the family Filoviridae.
Filoviruses cause severe filovirus hemorrhagic fever (FHF) in humans, with high
case fatality rates, and represent potential agents for bioterrorism and
biological weapons. It is necessary to keep surveillance of filoviruses, even
though there is no report of their isolation and patients in China so far. To
characterize MARV morphology, the Lake Victoria marburgvirus--Leiden was stained
negatively and observed under a transmission electron microscope which is one of
important detection methods for filoviruses in emergencies and bioterrorism. MARV
showed pleomorphism, with filamentous, rod-shaped, cobra-like, spherical, and
branch-shaped particles of uniform diameter but different lengths. Pleomorphism
of negatively stained MARV is summarized in this article, so as to provide useful
information for possible electron microscopic identification of filoviruses in
China.
PMID- 25118386
TI - [A review of detection methods for human bocaviruses].
AB - Human bocavirus (HBoV) 1-4 have been detected both in respiratory and stool
samples since the first HBoV was discovered in 2005. HBoV-1 is mostly associated
with respiratory infection, while HBoV 2-4 are usually associated with intestinal
tract infection. A variety of signs and symptoms have been described in patients
with HBoV infection, including cough, wheezing, pneumonia, and diarrhea, but the
research on pathogenic mechanism of HBoV is limited because HBoV cannot be
cultured in vitro due to the lack of appropriate host cells. Three-dimensional
epithelial cell culture, reverse genetics, and viral metagenomics are identified
as novel tools that may promote the research on pathogenic mechanism of HBoV and
the discovery of new viruses. This review summaries currently available
diagnostic approaches such as electron microscopy, cell culture, PCR, and
immunoassay in order to provide a method reference for indepth research on HBoV.
PMID- 25118387
TI - [Research progress in receptors involved in rotavirus infection].
AB - Rotaviruses, which are recognized as one of the major etiological agents among
infants and young children with diarrhea, consist of three concentric layers of
protein capsid with the enclosed double-stranded RNA genome. Rotaviruses infect
host cells mainly by identifying the specific receptors on cell surfaces and
binding to them. Therefore, receptors are important factors for viruses infecting
cells. So far, there have been many receptors found to be involved in rotavirus
infection, including sialic acid, integrin, Toll-like receptor, and blood group
antigen. This article provides an overview of receptors involved in rotavirus
infection.
PMID- 25118388
TI - [An overview of surveillance of avian influenza viruses in wild birds].
AB - Wild birds (mainly Anseriformes and Charadriiformes) are recognized as the
natural reservoir of avian influenza viruses (AIVs). The long-term surveillance
of AIVs in wild birds has been conducted in North America and Europe since 1970s.
More and more surveillance data revealed that all the HA and NA subtypes of AIVs
were identified in the wild ducks, shorebirds, and gulls, and the AIVs
circulating in wild birds were implicated in the outbreaks of AIVs in poultry and
humans. Therefore, the AIVs in wild birds pose huge threat to poultry industry
and human health. To gain a better understanding of the ecology and epidemiology
of AIVs in wild birds, we summarize the transmission of AIVs between wild birds,
poultry, and humans, the main results of surveillance of AIVs in wild birds
worldwide and methods for surveillance, and the types of samples and detection
methods for AIVs in wild birds, which would be vital for the effective control of
avian influenza and response to possible influenza pandemic.
PMID- 25118389
TI - [Advances in research on oncolytic adenoviruses in tumor therapy].
AB - Oncolytic adenoviruses (Ads), which are live, replication-competent viruses that
can selectively replicate in tumor cells and lead to cell lysis, have been used
in tumor therapy. But due to the complexity and high mutability of human tumors,
it becomes a major strategy to improve the selectivity, efficacy, and safety of
oncolytic Ads. The oncolytic Ads that can express short hairpin RNA, cytokines,
suicide gene, and matrix-modulating proteins have higher antitumor activity than
the wild type. Tumor-specific promoters, especially hTERT and HRE promoters,
increase the selectivity of oncolytic Ads for tumor cells. Moreover, oncolytic
Ads surface-modified by polyethylene glycol (PEG), liposomes, biodegradable
nanoparticles, and polypeptides have reduced immunogenicity and hepatotoxicity
and improved antitumor activity when systemically administered, and the
selectivity of oncolytic Ads can be significantly increased when linking PEG to
antibodies, small peptides, cytokines, and ligands. Therefore, engineered
oncolytic Ads combining the advantages of viral and non-viral vectors, as well as
immunotherapy, are a promising strategy for improving the efficacy of targeted
virotherapy.
PMID- 25118390
TI - [Research progress in functions of coronavirus accessory genes].
AB - In addition to the structural genes of the coronavirus genome, S, E, M, and N,
there are several additional genes called "group-specific or accessory genes".
Their gene products are designated as "accessory proteins", as reports to date
make it clear that these proteins are not essential for virus replication in
vitro. Nevertheless, many of these genes are still maintained in the virus genome
under selective pressure, suggesting that they might play a very important role
in the survival of the virus in the natural environment of the infected host.
This review will summarize the research progress in the functions of coronavirus
accessory genes.
PMID- 25118391
TI - [Studies on neuronal tracing with pseudorabies virus].
AB - With its abilities of trans-synaptic tracing and self-replication and wide host
range, pseudorabies virus (PRV) has been applied in the field of neuroanatomy
since the 1970s. Four decades of PRV application have made many advances in
researches on neuronal tracing with PRV. Mechanism studies focused on
investigating infection of primary neurons and tracing direction in secondary
neurons, while application studies focused on development of new pathological
strains and innovation of tracing techniques. To date, the mechanism and
application of viral tracing are not completely figured out yet. Integration of
molecular biology technology will improve the efficiency in related researches.
PMID- 25118392
TI - [Preface for special issue on biomass refinery (2014)].
AB - Biomass is the most abundant organic macromolecules in nature, which is expected
to achieve the brilliant of biorefinery equivalent to petroleum refining.
However, it is considered as the future industry to human due to the complicated
composition and transformation processes. The traditional lignocellulose bio
refining thoughts ignored the functional requirements of products, but spent a
lot of energies to destruct macromolecule into small molecules, and then
converted the small molecules into different products, which was high energy
consumption and low atom economy. How to realize the biorefinery of
lignocellulose is the key point and difficulty to achieve the biomass industry.
An ideal biorefinery of lignocellulose should as far as possibly to obtain the
maximum yield of each component, to maintain the integrity of the molecule, to
optimize the utilization of raw materials and finally to realize the maximum
value. Therefore, it requires the raw materials refining of lignocellosic biomass
should be based on the relationship of structure, process transformation and
related product characteristics. This special issue reports the latest advances
in the fields of raw material refinery, refining technologies, conversion
technologies of component.
PMID- 25118393
TI - [Sumac (Rhus chinensis Mill) biomass refinery engineering].
AB - Sumac (Rhus chinensis Mill) is an abundant and widely distributed Chinese native
plant. Sumac fruit contains low content of vegetable oil, as an atypical oil
plants hardly being processed through traditional vegetable oil production
technologies. Based on our own studies on the characteristics of sumac fruit and
branches, we established a novel model of sumac biomass refinery, and constructed
the sumac biomass refinery technology system and eco-industrial chain
integration. Steam explosion was the key technology, and several components
fractionation technologies were integrated in the sumac biomass refinery system.
The fractionated components were converted into different products depending on
their functional features. Eight products including sumac fruit oil, biodiesel,
protein feed, flavonoids, unbleached facial tissue, phenolic resin, biomass
briquette and biogas were produced in the refinery. The extracted sumac fruit oil
by steam explosion pretreatment was applied for the new food resource of Ministry
of Health, and the permit was approved. This research provides a new model for
the development of atypical wild plant resources.
PMID- 25118394
TI - [Effect of pretreatment on topochemical and ultrastructural changes of
lignocellulose plant cell walls: a review].
AB - Deconstruction of lignocellulosic plant cell walls to fermentable sugars by
biochemical means is impeded by several poorly understood ultrastructural and
chemical barriers. Pretreatment is an essential step by altering the
morphological and compositional characteristics of biomass to enhance the sugar
release during enzymatic hydrolysis. Therefore, getting insight into this field
is necessary to improve the conversion of biomass into biofuels. In this review,
we highlight our recent understanding on the impact of various promising
pretreatments on biomass, with emphasis on the topochemical and ultrastructural
changes of plant cell walls that are related to the reduction of recalcitrance
and the consequence of saccharification. It will lend support to the scientific
research and development with respect to biomass conversion.
PMID- 25118395
TI - [Application of process engineering to remove lignocellulose fermentation
inhibitors].
AB - Fermentation inhibitors are toxic to cells, which is one of the bottlenecks for
lignocellulose bio-refinery process. How to remove those inhibitors serves a key
role in the bioconversion of lignocellulose. This article reviews the sources and
the types of the inhibitors, especially the updated removal strategies including
physical methods, chemical methods, biological methods and inhibitor-tolerant
strain construction strategies. Based on these, we introduce a new bio-refinery
model named "fractional conversion", which reduces the production of inhibitors
at pretreatment stage, and a novel in situ detoxification method named
"fermentation promoter exploitation technology". This review could provide new
research ideas on the removal of fermentation inhibitors.
PMID- 25118396
TI - [Progress in natural laccase mediators from lignocelluloses].
AB - Laccase is one of the most important oxidoreductase with industrialization
potential. However, due to the high cost and catalytic toxicity of laccase
synthetic mediator, the laccase-mediator-system still cannot achieve
industrialization. Therefore, searching for high efficient, environment-friendly,
and cheap natural mediator from small molecule precursors or intermediates and
degradation products of lignin has been considered as a hot research topic.
Therefore, we introduce the type and catalytic mechanism of laccase mediator, the
composition and separation of natural laccase mediator from water washed solution
of steam exploded straw, black liquor and lignocelluloses degradation products
during the fermentation of white-rot fungi. We also provide the theoretical and
technical direction for exploring of high reactive of laccase natural mediators
and achieving the oriented high-value utilization of lignocellulose degradation
products.
PMID- 25118397
TI - [Degumming of kenaf fibers by combining steam explosion with ultrasonic
treatment].
AB - Kenaf has a high content of gum that is difficult to remove. Traditional chemical
degumming process causes serious environmental pollution. To solve the problem,
we developed a new method to degum kenaf. We pretreated the kenaf with steam
explosion followed by ultrasonic treatment. We chose the single factor tests to
select the ultrasonic frequency, sodium hydroxide concentration and processing
time. Combined with orthogonal tests, we found that the optimum conditions were
as follows: ultrasonic frequency was 28 kHz, sodium hydroxide concentration was
2%, and processing time was 60 min. Under these conditions, the residual gum of
kenaf fiber was 9.72% and the fineness was 139.45 N(m). Steam explosion combined
with ultrasonic method is effective in degumming of kenaf.
PMID- 25118398
TI - [Low temperature plasma technology for biomass refinery].
AB - Biorefinery that utilizes renewable biomass for production of fuels, chemicals
and bio-materials has become more and more important in chemical industry.
Recently, steam explosion technology, acid and alkali treatment are the main
biorefinery treatment technologies. Meanwhile, low temperature plasma technology
has attracted extensive attention in biomass refining process due to its unique
chemical activity and high energy. We systemically summarize the research
progress of low temperature plasma technology for pretreatment, sugar platflow,
selective modification, liquefaction and gasification in biomass refinery.
Moreover, the mechanism of low temperature plasma in biorefinery and its further
development were also discussed.
PMID- 25118399
TI - [Effect of byproducts in lignocellulose hydrolysates on ethanol fermentation by
Issatchenkia orientalis].
AB - Byproducts in lignocellulose hydrolysates, namely sodium formate (1 to 5 g/L),
sodium acetic (2.5 to 8.0 g/L), furfural (0.2-2 g/L), 5-hydroxymethylfurfural (5
HMF, 1 to 1.0 g/L) or vanillin (0.5 to 2 g/L) were used to evaluate their effects
on ethanol fermentation by Issatchenkia orientalis HN-1 using single factor test
and the response surface central composite experiment. Results showed that most
of the byproducts had no obvious inhibition on the production of ethanol, except
for the addition of 2 g/L vanillin or 1 g/L of 5-HMF, which reduced the ethanol
production by 20.38% and 11.2%, respectively. However, high concentration of some
byproducts in lignocellulose hydrolysates, such as sodium formate (1 to 5 g/L),
sodium acetic (2.5 to 8.0 g/L), furfural (0.2 to 2 g/L) and vanillin (0.5 to 2
g/L) inhibited the growth of I. orientalis HN-1 significantly. Compared with the
control, the dry cell weight of I. orientalis HN-1 decreased by 25.04% to 37.02%,
28.83% to 43.82%, 20.06% to 37.60% and 26.39% to 52.64%, respectively, when the
above components were added into the fermentation broth and the fermentation
lasted for 36 h. No significant interaction effect of the various inhibitors
(sodium formate, sodium acetic, furfural and vanillin) except for vanillin single
factor on the ethanol production was observed based on the central composite
experiments. The concentrations of byproducts in most lignocellulose hydrolysates
were below the initial inhibition concentration on ethanol production by
Issatchenkia orientalis HN-1, which indicated that Issatchenkia orientalis HN-1
can be used for ethanol production from lignocellulose hydrolysates.
PMID- 25118400
TI - [Pretreatment of industrial lignin and catalytic conversion into phenol].
AB - Recent concerns about the gradual depletion of conventional fossil resources and
the pressure from global climate change have accentuated the need for new
alternative feedstock. As one of the main components in biomass, lignin is the
second most abundant natural polymer after cellulose, and has the potential to
serve as a sustainable source of energy and organic carbon to replace petroleum
based chemicals. Efficient conversion of lignin into high value-added chemicals
is crucial to improve the economic feasibility of biomass refinery. In the
present study, several pretreatment technologies on industrial lignin were
carried out to enhance phenol production. A microwave irradiation assisted
biphasic reaction system was used to convert pretreated industrial lignin into
phenolic compounds. Lignin conversion, reaction temperature, time and
pretreatment method, were optimized. The highest phenol yield was 8.14% obtained
from lignin pretreated by 1-ethyl-3-methylimidazolium acetate at 400 W for 60 min
in a biophasic system catalyze by 1-aminoethyl-3-methylimidazolium
tetrafluoroborate.
PMID- 25118401
TI - [Pretreatment of ramie and kenaf stalk for bioethanol production].
AB - Ramie and kenaf were traditional fiber crops in China, but their stalk after
decorticating has not been used effectively. The stalk contains a lot of
cellulose, and can therefore be used for the production of bioethanol. We studied
the effects of different chemical pretreatment on enzymatic digestibility of
ramie stalk and kenaf stalk. Ramie and kenaf stalks pretreated with alkali were
chosen to produce ethanol using quasi-simultaneous saccharification and
fermentation (Q-SSF) process. The results show that for the stalks pretreated
with 4% NaOH and 0.02% anthraquinone-2-sulfonic acid sodium salt (AQSS) as
catalyzer at 170 degrees C for 1 h, the ethanol concentration could reach 51 g/L
after fermentation for 168 h at 18% of solid substrate concentration. By fed
batch to 20% of solid substrate concentration, the ethanol concentration could
reach 63 g/L, 77% and 79% of the cellulose conversion could get for ramie stalk
and kenaf stalk, respectively. For kenaf stalk pretreated with 5.2% NaHSO3 and
0.2% H2SO4 at 170 degrees C for 1 h, the ethanol concentration and cellulose
conversion could reach to 65 g/L and 72%, respectively.
PMID- 25118402
TI - [Effect of non-ionic surfactants on butanol production with Clostridium
acetobutylicum ATCC 824].
AB - The low butanol concentration of acetone-butanol-ethanol fermentation causes
uneconomical product recovery. In this work, the effect of small molecule non
ionic surfactants on butanol fermentation was evaluated, using laboratory stocks
of Clostridium acetobutylicum ATCC 824. Non-ionic surfactants substantially
increased butanol production when additive amount was higher than 1% (W/W).
Butanol concentration reached 16.9 g/L with 5% (W/W) Tween 80 and 100 g/L glucose
in a 5 L fermenter. It was found that surfactants micelle solubilization capacity
to butanol was very limited, indicating that butanol could hardly enter the
surfactants micelle. Butanol production improvement was probably caused by cell
surface hydrophobicity change due to surfactants adsorption.
PMID- 25118403
TI - A new species and species-group of Simulium (Simulium) (Diptera: Simuliidae) from
Thailand.
AB - Simulium (Simulium) atipornae sp. nov. is described from females, males, pupae,
and larvae in Thailand. This new species is characterized in the female by the
claw with a small subbasal tooth, ovipositor valve triangular with its inner
margin nearly straight; in the male by the style with a short subbasal
protuberance and ventral plate Y-shaped, with toothed posterior margin; and in
the pupa by the head and thoracic integument almost bare and gill with six
filaments. Taxonomic notes are given to compare this new species with nine
related species. A new species-group, the christophersi species-group, is
proposed to accommodate S. atipornae sp. nov. and nine related species.
PMID- 25118404
TI - Environmental factors related to the abundance and activity of Ochlerotatus
albifasciatus (Diptera: Culicidae) in an agricultural landscape of steppe arid
climate.
AB - Ochlerotatus albifasciatus (Macquart) is a flood water mosquito whose highest
density has been found associated both with natural landscapes (prairies or
grazing fields) in temperate and subtropical regions and with rainfall events. In
the current study, we aimed to find out how the marked differences between
environmental factors of agricultural landscape patches in a steppe arid region
affect the relative abundance of this species. In wetland patches, the high
activity of adults was closely associated with the flood irrigation system,
suggesting that the agricultural activity contributes to the proliferation of
this mosquito. The steppe patches would constitute an adverse environment
reflected by the abrupt decrease in abundance. Multiple linear regression showed
that some explanatory variables, such as wetland patches and moment of the day
(midday), did not contribute significantly to the relative abundance variation.
In contrast, temperature, wind, and cloud cover seemed to regulate the biting
activity of females. Temperature affected the activity of mosquitoes in the
steppe but seemed to have no effect in wetland patches, where the activity of
mosquitoes was permanent and more stable against changes in temperature. In the
steppe, which presents low levels of humidity, scarce vegetation, and greater
wind exposure, the activity seemed to be unstable against small thermal
variations. The variability of the relative abundance of Oc. albifasciatus in an
agricultural landscape was widely explained by temperature in combination with
the microenvironment type, wind speed, and cloud cover and indirectly by human
activity.
PMID- 25118405
TI - Intra-annual changes in abundance of Aedes (Stegomyia) aegypti and Aedes
(Ochlerotatus) epactius (Diptera: Culicidae) in high-elevation communities in
Mexico.
AB - We examined temporal changes in the abundance of the mosquitoes Aedes (Stegomyia)
aegypti (L.) and Aedes (Ochlerotatus) epactius Dyar & Knab from June to October
2012 in one reference community at lower elevation (Rio Blanco; approximately
1,270 m) and three high-elevation communities (Acultzingo, Maltrata, and Puebla
City; 1,670-2,150 m) in Veracruz and Puebla States, Mexico. The combination of
surveys for pupae in water-filled containers and trapping of adults, using BG
Sentinel traps baited with the BG-Lure, corroborated previous data from 2011
showing that Ae. aegypti is present at low abundance up to 2,150 m in this part
of Mexico. Data for Ae. aegypti adults captured through repeated trapping in
fixed sites in Acultzingo--the highest elevation community (approximately 1,670
m) from which the temporal intra-annual abundance pattern for Ae. aegypti has
been described--showed a gradual increase from low numbers in June to a peak
occurrence in late August, and thereafter declining numbers in September. Ae.
epactius adults were collected repeatedly in BG-Sentinel traps in all four study
communities; this is the first recorded collection of this species with a trap
aiming specifically to collect human-biting mosquitoes. We also present the first
description of the temporal abundance pattern for Ae. epactius across an
elevation gradient: peak abundance was reached in mid-July in the lowest
elevation community (Rio Blanco) but not until mid-September in the highest
elevation one (Puebla City). Finally, we present data for meteorological
conditions (mean temperature and rainfall) in the examined communities during the
study period, and for a cumulative measure of the abundance of adults over the
full sampling period.
PMID- 25118406
TI - Effect of diet quality on survival and reproduction of adult Paederus fuscipes
(Coleoptera: Staphylinidae).
AB - The survival and reproduction of the beetle Paederus fuscipes Curtis on diets
that differed in macronutrient composition were investigated in the laboratory.
The sex organs of females fed each test diet were dissected to evaluate the
ovarian development over time. Adults fed on a carbohydrate-rich diet lived
longer than adults fed the other diets, but this diet provided insufficient
nutrients for reproduction. Females fed on a protein-rich diet had high
fecundity; however, the mean longevity of reproductive adult P. fuscipes
significantly was shortened by 20-30 d compared with longevity of 60-70 d for
adults fed a carbohydrate-rich diet. In contrast, adults that were provided lipid
rich diet had low survival and fecundity. Overall, the development
ofprevitellogenic follicles was significantly affected by diet regime and days
since starting a particular diet. The follicle size of females given protein-rich
diet increased 0.5-fold 2 wk after beginning the diet. In contrast, the
development of the follicles was slow in females given the carbohydrate-rich diet
and the follicles degenerated in females given the lipid-rich diet. In terms of
ovarian maturation, females fed on a protein-rich diet contained mostly
vitellogenic and chorionated follicles. In contrast, the ovarioles of females on
the carbohydrate-rich diet were largely occupied with previtellogenic and
vitellogenic follicles, whereas for a lipid-rich diet, the follicles remained at
the previtellogenic stage throughout the experiment.
PMID- 25118407
TI - Seasonal and spatial oviposition activity of Aedes albopictus (Diptera:
Culicidae) in Adriatic Croatia.
AB - Seasonal and spatial ovipositional activity of Aedes albopictus (Skuse, 1894) was
investigated in Split, South Croatia. During 2009 and 2010, 35 oviposition traps
were used in this research. For studying oviposition behavior, mean egg density
and Lloyd's mean crowding were used to define the dispersion of eggs into
ovitraps and, together with Taylor's power law, to show aggregation degree. To
show monthly distribution of egg density, Kriging interpolation was used.
Oviposition activity started in April (week 13) and was completed at the
beginning December (week 48). Mean egg density reaches the highest values from
June to early September (week 25-35). Slope of regressions (mean crowding on mean
density and log variance and log mean density) indicated a clumped distribution
of eggs. Sampling sites were divided in four groups based on quartiles of median
and maximum of mean density. There was no significant difference in measured
abiotic factors (temperature, humidity, and rainfall) and measured mean egg
density, total amount of eggs, and percentage of positive ovitraps between
investigated years, except in mean egg density in some localities.
PMID- 25118409
TI - The relationship between deer density, tick abundance, and human cases of Lyme
disease in a residential community.
AB - White-tailed deer (Odocoileus virginianus Zimmerman), serve as the primary host
for the adult blacklegged tick (Ixodes scapularis Say), the vector for Lyme
disease, human babesiosis, and human granulocytic anaplasmosis. Our objective was
to evaluate the degree of association between deer density, tick abundance, and
human cases of Lyme disease in one Connecticut community over a 13-yr period. We
surveyed 90-98% of all permanent residents in the community six times from 1995
to 2008 to document resident's exposure to tick-related disease and frequency and
abundance of deer observations. After hunts were initiated, number and frequency
of deer observations in the community were greatly reduced as were resident
reported cases of Lyme disease. Number of resident-reported cases of Lyme disease
per 100 households was strongly correlated to deer density in the community.
Reducing deer density to 5.1 deer per square kilometer resulted in a 76%
reduction in tick abundance, 70% reduction in the entomological risk index, and
80% reduction in resident-reported cases of Lyme disease in the community from
before to after a hunt was initiated.
PMID- 25118408
TI - Relative humidity and activity patterns of Ixodes scapularis (Acari: Ixodidae).
AB - Laboratory studies have shown clear relationships between relative humidity (RH)
and the activity and survival of Ixodes scapularis Say (blacklegged tick).
However, field studies have produced conflicting results. We examined this
relationship using weekly tick count totals and hourly RH observations at three
field sites, stratified by latitude, within the state of Rhode Island. Records of
nymphal tick abundance were compared with several RH-related variables (e.g., RH
at time of sampling and mean weekly daytime RH). In total, 825 nymphs were
sampled in 2009, a year of greater precipitation, with a weighted average leaf
litter RH recorded at time of sampling of 85.22%. Alternatively, 649 nymphs were
collected in 2010, a year of relatively low precipitation, and a weighted average
RH recorded at time of sampling was 75.51%. Negative binomial regression analysis
of tick count totals identified cumulative hours < 82% RH threshold as a
significant factor observed in both years (2009: P = 0.0037; 2010: P < 0.0001).
Mean weekly daytime RH did not significantly predict tick activity in either
year. However, mean weekly daytime RH recorded with 1-wk lag before sample date
was a significant variable (P = 0.0016) in 2010. These results suggest a lag
effect between moisture availability and patterns of tick activity and abundance.
Differences in the relative importance of each RH variable between years may have
been due to abnormally wet summer conditions in 2009.
PMID- 25118410
TI - Comparison of efficacy of five types of long-lasting insecticidal nets against
Anopheles fluviatilis, the primary malaria vector in east-central India.
AB - Five types of long-lasting insecticidal nets (LNs), namely, Olyset, Netprotect,
PermaNet, DuraNet, and Interceptor, were tested after 20 washes for efficacy in
terms of mortality, deterrence effect, blood-feeding inhibition, and induced
exophily of the malaria vector Anopheles fluviatilis in experimental huts in
Malkangiri district of Odisha State, India. Efficacy of the three synthetic
pyrethroids (SPs) used in the LNs was also analyzed. Use of LNs reduced the entry
of An. fluviatilis into the huts by 73.3-83.2%, and the five LNs were comparable
in terms of deterrence. The exit rate of An. fluviatilis from the huts with
untreated net was 56.3%, and relative to this, Olyset followed by DuraNet induced
significantly a higher exophily. In contrast, the exit rate was significantly
lower with Interceptor. Among the three SPs, permethrin induced significantly
greater exophily relative to the untreated control, and as a result of this,
permethrin-treated Olyset produced a lower mortality. Blood-feeding rate of An.
fluviatilis was significantly lower with all the five LNs than the control.
Similarly, all the three SPs significantly inhibited blood feeding compared with
the control. Interceptor and DuraNet, both alphacypermethrin-treated LNs, caused
relatively a higher mortality of An. fluviatilis than the other LNs. The five
brands of LNs and three SPs tested in the current study were equally effective in
terms of deterrence and blood-feeding inhibition; only exiting and killing effect
differed among them. Permethrin-treated LNs induced greater exophily, while,
overall, alphacypermethrin-treated LNs killed more An. fluviatilis that entered
the huts. Advantage of deterrence, excito-repellent, and killing effects of LNs
and appropriate selection of SP for net treatment are discussed in this paper.
PMID- 25118411
TI - Multiplex qPCR assay for identification and differentiation of Amblyomma
americanum, Amblyomma cajennense, and Amblyomma maculatum (Ixodida: Ixodidae)
tick species in the eastern United States.
AB - Many ticks of the genus Amblyomma are vectors of human pathogens, and the correct
species identification is medically and epidemiologically important.
Morphological identification is time-consuming and requires a high level of
expertise. Identification of engorged, immature, or damaged ticks and the
differentiation of closely related species remain problematic. Here, we report
the development of a real-time TaqMan assay for the genomic identification and
differentiation of Amblyomma americanum (L.), Amblyomma cajennense (F.), and
Amblyomma maculatum (Koch), which are human-biting species found in the eastern
United States. New species-specific sets of oligonucleotides for the multiplex
reaction that detect and differentiate the ITS2 genomic regions of three target
species were designed using Visual OMP; the previously published A. americanum
oligonucleotide set was also incorporated into our assay. Specificity and
sensitivity tests for two multiplex master mixes using different A. americanum
sets were performed using individual and pooled samples of adult, nymphal, and
larval ticks, and optimization procedures were applied. The multiplex assay
successfully differentiates between genomes of three target species and does not
cross-react with DNAs of ticks from other genera. Rare cases of nonspecific
amplification occurred with DNAs of A. imitator and Amblyomma triste Koch
misidentified as A. americanum and A. maculatum, respectively. However, this
cross-reaction does not diminish the usefulness of the developed assay east of
the 95th meridian, where neither A. imitator nor A. triste are found. Two master
mixes incorporating the previously published or newly developed A. americanum
sets are being recommended for identification of individual ticks or pooled
samples, respectively.
PMID- 25118412
TI - Enhanced toxicity of binary mixtures of Bacillus thuringiensis subsp. israelensis
and three essential oil major constituents to wild Anopheles sinensis (Diptera:
Culicidae) and Aedes albopictus (Diptera: Culicidae).
AB - An assessment was made of the toxicity of 12 insecticides and three essential
oils as well as Bacillus thuringiensis subsp. israelensis (Bti) alone or in
combination with the oil major constituents (E)-anethole (AN), (E)
cinnamaldehyde (CA), and eugenol (EU; 1:1 ratio) to third instars of bamboo
forest-collected Aedes albopictus (Skuse) and rice paddy field-collected
Anopheles sinensis Wiedemann. An. sinensis larvae were resistant to various
groups of the tested insecticides. Based on 24-h LC50 values, binary mixtures of
Bti and CA, AN, or EU were significantly more toxic against Ae. albopictus larvae
(0.0084, 0.0134, and 0.0237 mg/liter) and An. sinensis larvae (0.0159, 0.0388,
and 0.0541 mg/liter) than either Bti (1.7884 and 2.1681 mg/liter) or CA (11.46
and 18.56 mg/liter), AN (16.66 and 25.11 mg/liter), or EU (24.60 and 31.09
mg/liter) alone. As judged by cotoxicity coefficient (CC) and synergistic factor
(SF), the three binary mixtures operated in a synergy pattern (CC, 140.7-368.3
and SF, 0.0007-0.0010 for Ae. albopictus; CC, 75.1-245.3 and SF, 0.0008-0.0017
for An. sinensis). Global efforts to reduce the level of highly toxic synthetic
insecticides in the aquatic environment justify further studies on the binary
mixtures of Bti and essential oil constituents described, in particular CA, as
potential larvicides for the control of malaria vector mosquito populations.
PMID- 25118413
TI - X-ray-induced sterility in Aedes albopictus (Diptera: Culicidae) and male
longevity following irradiation.
AB - The mosquito Aedes albopictus (Skuse, 1895) is a potent vector of several
arboviral diseases, most notably chikungunya and dengue fever. In the context of
the sterile insect technique (SIT), the sterilization of the male mosquitoes
before their release can be achieved by gamma-ray irradiation. As gamma-ray
irradiators are becoming increasingly problematic to purchase and transport, the
suitability of an X-ray irradiator as an alternative for the sterilization of Ae.
albopictus males was studied. The sterilization of up to 200,000 pupae at one
time can be achieved with relative ease, and the sterility results obtained were
comparable with those achieved by gamma irradiation, where 99% sterility is
induced with a dose of 40 Gy. A significant reduction of longevity was observed
in the latter stages of the males' life after irradiation treatments, especially
at doses > 40 Gy, which is consistent with the negative effects on longevity
induced by similar radiation doses using gamma rays. Females irradiated at 40 Gy
were not only 100% sterile, but also failed to oviposit entirely, i.e., all of
the females laid 0 eggs. Overall, it was found that the X-ray irradiator is
generally suitable for the sterilization process for sterile insect technique
programs, as it showed a high processing capacity, practicality, high
effectiveness, and reproducibility.
PMID- 25118414
TI - Predation and control efficacies of Misgurnus mizolepis (Cypriniformes:
Cobitidae) toward Culex pipiens molestus (Diptera: Culicidae) and fish toxicity
of temephos in laboratory and septic tank conditions.
AB - Culex pipiens molestus Forskal (Diptera: Culicidae) is the dominant mosquito
species in septic tanks in South Korea. An assessment was made of the biological
control potential of mud loaches, Misgurnus mizolepis Gunther (Cypriniformes:
Cobitidae), toward Cx. p. molestus larvae in laboratory and septic tanks. Results
were compared with those of temephos 20% emulsifiable concentrate. In laboratory
tests, all mud loaches survived on sedimentation chamber- and effluent chamber
collected water of aerobic septic tanks (ASTs), whereas all mud loaches died
within 3-12 h after introduction into sedimentation chamber- and effluent chamber
collected water of anaerobic septic tanks, Gill hyperplasia and hemorrhages at
the bases of pectoral fins were detected in all dead mud loaches. These appeared
to have been caused by bacterial disease, rather than the physical and chemical
characteristics of the septic tank water. A mud loach consumed an average range
of 1,072-1,058 larvae of Cx. p. molestus in the AST water at 24 h. At the
manufacturer's recommended rate (10 ml/ton) in the AST water, the temephos
formulation did not cause fish mortality. In the AST experiment, predation of
mosquito larvae by mud loaches at a release rate of one fish per 900 mosquito
larvae resulted in complete mosquito control from the third day after treatment
throughout the 18-wk survey period, compared with temephos 20% emulsifiable
concentrate-treated AST water (reduction rate, 40% at 28 days after treatment).
Reasonable mosquito control in aerobic septic tanks can be achieved by mosquito
breeding season stocking of a rate of one mud loach per 900 mosquito larvae.
PMID- 25118415
TI - Chemical composition, larvicidal, and biting deterrent activity of essential oils
of two subspecies of Tanacetum argenteum (Asterales: Asteraceae) and individual
constituents against Aedes aegypti (Diptera: Culicidae).
AB - Water-distilled essential oils from dried aerial parts of Tanacetum argenteum
(Lam.) Willd. subsp. argenteum (Lam.) and T. argenteum (Lam.) Willd. subsp. canum
(C. Koch) Grierson were analyzed by gas chromatography and gas chromatography
mass spectrometry. In total, 27 and 32 components were identified representing
97.2 and 98.7% of essential oils of subsp. argenteum and canum, respectively.
Main compounds of T. argenteum subsp. argenteum were alpha-pinene (67.9%) and
beta-pinene (4.8%), whereas alpha-pinene (53.6%), 1, 8-cineole (14.8%), and
camphor (4.7%) were the major constituents of subsp. canum. Essential oil of T.
argenteum subsp. canum at 10 microg/cm2 with Biting Deterrent Index (BDI) value
of 0.73 showed activity similar to N,N-Diethyl-meta-toluamide (DEET) at 25
mol/cm2, whereas the activity of essential oil of subsp. argenteum was lower (BDI
= 0.47) than subsp. canum and DEET. Based on 95% CIs, activity of beta
caryophyllene (BDI value = 0.54) and caryophyllene oxide (BDI = 0.66) were
significantly lower than DEET. In larval bioassays, essential oil of T. argenteum
subsp. argenteum showed LC50 value of 93.34 ppm, whereas T. argenteum subsp.
canum killed only 40% of the larvae at the highest dose of 125 ppm. Among the
pure compounds, beta-caryophyllene (LC50 = 26 ppm) was the most potent compound
followed by caryophyllene oxide (LC50 = 29 ppm), which was also similar to (-)
beta-pinene (LC50 = 35.9 ppm) against 1-d-old Ae. aegypti larvae at 24-h post
treatment. Compounds (-)-alpha-pinene and (+)-beta-pinene showed similar
larvicidal activity. Activity of (+)-alpha-pinene with LC50 value of was similar
to the essential oil of T. argenteum subsp. argenteum.
PMID- 25118416
TI - A user friendly method to assess Anopheles stephensi (Diptera: Culicidae) vector
fitness: fecundity.
AB - Fecundity, bloodmeal size, and survival are among the most important parameters
in the overall fitness of mosquitoes. Impact of an intervention that affects
fecundity can be assessed by directly counting the eggs laid by exposed
mosquitoes, which is usually done manually. We have developed a macroinstruction,
which can be used to count thousands of Anopheles stephensi Liston eggs in a few
minutes, to provide an alternative and adaptable method to egg counting as a
measure of fecundity. The macro was developed using a scanner and a computer
running AxioVision Rel. 4.8 software, a freely accessible software compatible
with Windows XP/7/Vista. Using this semiautomated method, it is possible to
reduce time, avoid human error and bias, and obtain improved consistency in
studies measuring mosquito fecundity.
PMID- 25118417
TI - Laboratory and field evaluation of spinosad formulation Natular T30 against
immature Culex mosquitoes (Diptera: Culicidae).
AB - Spinosad consisting of spinosyn A and D is derived from a naturally occurring,
soil-dwelling bacterium, Saccharopolyspora spinosa. Spinosyns are neurotoxins
that activate postsynaptic nicotinic acetylcholine and gamma-aminobutyric acid
receptors and cause rapid excitation of the insect nervous system and ultimately
exhaustion and death of the targets. During the past 30 yr, numerous spinosad
based formulations have been developed and applied to control various arthropod
pests of agricultural importance. Natular T-30 is a new slow-release formulation
containing 8.33% spinosad for use in mosquito larval control programs. High-level
larvicidal activity, as indicated by low LC50 and LC90 levels, was demonstrated
against Culex quinquefasciatus Say in the laboratory. Larvicidal efficacy was
evaluated in semifield microcosms, field mesocosms, and underground storm drains.
Fair performance against larval populations of Culex spp. and other mosquito
species was achieved, although low efficacy during the initial few days
posttreatment was encountered. This slow-release formulation will play an
important role in controlling mosquitoes in persistent breeding sources.
PMID- 25118418
TI - Exploring new thermal fog and ultra-low volume technologies to improve indoor
control of the dengue vector, Aedes aegypti (Diptera: Culicidae).
AB - Control of the mosquito vector, Aedes aegypti (L.), inside human habitations must
be performed quickly and efficiently to reduce the risk of transmission during
dengue outbreaks. As part of abroad study to assess the efficacy of dengue vector
control tools for the U.S. Military, two pesticide delivery systems (ultra-low
volume [ULV] and thermal fog) were evaluated for their ability to provide
immediate control of Ae. aegypti mosquitoes with a contact insecticide inside
simulated urban structures. An insect growth regulator was also applied to
determine how well each sprayer delivered lethal doses of active ingredient to
indoor water containers for pupal control. Mortality of caged Ae. aegypti,
pesticide droplet size, and droplet deposition were recorded after applications.
In addition, larval and pupal mortality was measured from treated water samples
for 4 wk after the applications. The ULV and the thermal fogger performed equally
well in delivering lethal doses of adulticide throughout the structures. The ULV
resulted in greater larval mortality and adult emergence inhibition in the water
containers for a longer period than the thermal fogger. Therefore, the ULV
technology is expected to be a better tool for sustained vector suppression when
combined with an effective insect growth regulator. However, during a dengue
outbreak, either delivery system should provide an immediate knockdown of vector
populations that may lower the risk of infection and allow other suppression
strategies to be implemented.
PMID- 25118420
TI - First record of Ixodes arboricola (Ixodida: Ixodidae) from Turkey with presence
of Candidatus Rickettsia vini (Rickettsiales: Rickettsiaceae).
AB - Birds are the specific hosts of many tick species and may contribute to the
dissemination of ticks and tick-borne pathogens throughout the world.
Determination of ticks infesting birds and their pathogens are important for the
detection of natural foci of human pathogens. Unfortunately, there is very
limited information about the occurrence of ticks on birds and associated
pathogens in Turkey. We performed a tick survey on three passerine bird species;
Parus major, Sylvia atricapilla, and Turdus merula. Ticks collected from these
birds were identified to species and tested for the presence of Borrelia,
Ehrlichia, and Rickettsia species. Ixodes arboricola Schulze & Schlottke, Ixodes
frontalis Panzer, and Ixodes ricinus L. were found on the birds. This is the
first study reporting the presence of I. frontalis and I. arboricola on S.
atricapilla and P. major, respectively, in Turkey. In addition, the results of
polymerase chain reaction (PCR) with primers specific for gltA and ompA genes and
DNA sequence analysis of positive PCR products indicated the presence of
Candidatus Rickettsia vini in I. arboricola ticks. In conclusion, this is the
first record of both I. arboricola and Candidatus Rickettsia vini in Turkey.
Therefore, future studies needed to be conducted on the ticks infesting birds and
their pathogens to elucidate the role of birds in the dispersal of tick species
and tick-borne pathogens in Turkey.
PMID- 25118419
TI - Feeding by Amblyomma maculatum (Acari: Ixodidae) enhances Rickettsia parkeri
(Rickettsiales: Rickettsiaceae) infection in the skin.
AB - Rickettsia parkeri Luckman (Rickettsiales: Rickettsiaceae), a member of the
spotted fever group of Rickettsia, is the tick-borne causative agent of a newly
recognized, eschar-associated rickettsiosis. Because of its relatively recent
designation as a pathogen, few studies have examined the pathogenesis of
transmission of R. parkeri to the vertebrate host. To further elucidate the role
of tick feeding in rickettsial infection of vertebrates, nymphal Amblyomma
maculatum Koch (Acari: Ixodidae) were fed on C3H/HeJ mice intradermally
inoculated with R. parkeri (Portsmouth strain). The ticks were allowed to feed to
repletion, at which time samples were taken for histopathology,
immunohistochemistry (IHC), quantitative polymerase chain reaction (qPCR) for
rickettsial quantification, and reverse transcriptase polymerase chain reaction
(RT-PCR) for expression of Itgax, Mcp1, and Il1beta. The group of mice that
received intradermal inoculation of R. parkeri with tick feeding displayed
significant increases in rickettsial load and IHC staining, but not in cytokine
expression, when compared with the group of mice that received intradermal
inoculation of R. parkeri without tick feeding. Tick feeding alone was associated
with histopathologic changes in the skin, but these changes, and particularly
vascular pathology, were more pronounced in the skin of mice inoculated
previously with R. parkeri and followed by tick feeding. The marked differences
in IHC staining and qPCR for the R. parkeri with tick feeding group strongly
suggest an important role for tick feeding in the early establishment of
rickettsial infection in the skin.
PMID- 25118421
TI - Detection of bacterial agents in Amblyomma americanum (Acari: Ixodidae) from
Georgia, USA, and the use of a multiplex assay to differentiate Ehrlichia
chaffeensis and Ehrlichia ewingii.
AB - Amblyomma americanum, the lone star tick, is the most common and most aggressive
human biting tick in the Southeastern United States. It is known to transmit the
agents of human ehrlichioses, Ehrlichia chaffeensis and Ehrlichia ewingii. In
addition, it carries agents of unspecified pathogenicity to humans, including
Rickettsia amblyommii, Borrelia lonestari, and the newly emerging Panola Mountain
Ehrlichia (PME). Surveillance of these ticks for recognized or emerging pathogens
is necessary for assessing the risk of human infection. From 2005 to 2009, we
surveyed A. americanum ticks from four locations in the state of Georgia. Ticks
(1,183 adults, 2,954 nymphs, and 99 larval batches) were tested using a multiplex
real-time polymerase chain reaction (PCR) assay designed to detect and
discriminate DNA from Rickettsia spp., E. chaffeensis, and E. ewingii. This assay
was capable of detecting as few as 10 gene copies of the aforementioned agents.
Ticks were also tested for PME and B. lonestari by nested PCR. The prevalence of
infection ranged from 0 to 2.5% for E. chaffeensis, 0 to 3.9% for E. ewingii, 0
to 2.2% for PME, 17 to 83.1% for R. amblyommii, and 0 to 3.1% for B. lonestari.
There were 46 (4.1%) individual adults positive for two agents, and two females
that were each positive for three agents. Two larval batches were positive for
both B. lonestari and R. amblyommii, indicating the potential for transovarial
transmission of both agents from a single female. Although infrequent in
occurrence, the dynamics of coinfections in individual ticks should be explored
further, given the potential implications for differential diagnosis and severity
of human illness.
PMID- 25118422
TI - Efficacy of novaluron as a feed-through for control of immature horn flies, house
flies, and stable flies (Diptera: Muscidae) developing in cow manure.
AB - Two rates (0.4 mg/kg body weight/d and 0.6 mg/kg body weight/d) of a daily feed
through formulation of novaluron (Novaluron 0.67% active ingredient Cattle Mix),
a newer benzoylphenyl urea insecticide, were evaluated for efficacy in
controlling the larval stage of horn flies, Haematobia irritans (L.), house
flies, Musca domestica L., and stable flies, Stomoxys calcitrans (L.), developing
in cow manure. Both rates of feed-through novaluron, delivered consecutively for
10 d, reduced adult emergence of all three species when compared with the
untreated control. The presence of deformed puparia indicated that novaluron had
an insect growth regulator effect on the developing fly larvae. Both of the feed
through rates evaluated resulted in 100% reduction of adult stable fly emergence
after the second day of feed-through treatment. The level of control efficacy
observed against these three fly species make this feed-through formulation a
candidate for use in an integrated livestock pest management program,
particularly in confined cattle production situations where a feed-through
product could be easily administered.
PMID- 25118423
TI - A silicone membrane for in vitro feeding of Ixodes scapularis (Ixodida:
Ixodidae).
AB - We describe a simple silicone membrane for in vitro feeding of Ixodes scapularis
(Say), the main tick vector of Lyme borreliosis in the United States. Membranes
are prepared using regenerated cellulose lens paper, which is coated with a
controlled layer of silicone by submerging and removing the paper in a defined
solution of silicone glue dissolved in toluene. Median engorged weight obtained
by I. scapularis fed on defibrinated bovine blood using these membranes was 109
mg (32-198 mg). These ticks laid eggs in the laboratory and larvae hatched 6 wk
later. This method simplifies artificial membranes for in vitro feeding of ixodid
ticks, which have long required a considerable amount of skill and experience to
prepare.
PMID- 25118424
TI - Feeding host range of Aedes albopictus (Diptera: Culicidae) demonstrates its
opportunistic host-seeking behavior in rural Singapore.
AB - Aedes albopictus (Skuse) is a competent vector of arboviruses of public health
importance, including dengue virus (DENV) and chikungunya virus viruses. Ae.
albopictus is the primary vector of chikungunya virus in Singapore. However,
despite being ubiquitous, it plays a secondary role in DENV transmission. The
vectorial capacity of Ae. albopictus for DENV in field settings appears to be
weak because dengue primarily occurs in Aedes aegypti (L.)-dominated, urban
settings of the country. As host-seeking behavior is one of the determinants of
vectorial capacity, we screened 6,762 female Ae. albopictus from rural,
semiurban, and urban locations in Singapore for avian and nonavian bloodmeals
using two polymerase chain reaction-sequencing assays developed in-house. The
majority (83.2%, n = 79) of bloodmeals from rural and semiurban areas were from
humans. However, Ae. albopictus was also found to feed on shrews, swine, dogs,
cats, turtles, and multiple hosts in rural settings. In urban areas, all positive
bloodmeals were from humans. There were no avian bloodmeals. Our findings testify
that Ae. albopictus is highly anthropophagic even in rural settings, but become
opportunistic in extremely low human abundance. This opportunistic feeding
behavior warrants further investigations into the vectorial capacity of Ae.
albopictus to assess its role in arbovirus transmission in endemic habitats.
PMID- 25118425
TI - Temporal correlations between mosquito-based dengue virus surveillance measures
or indoor mosquito abundance and dengue case numbers in Merida City, Mexico.
AB - Surveillance of dengue virus (DENV) in Aedes (Stegomyia) aegypti (L.) females is
of potential interest because human DENV infections are commonly asymptomatic,
which decreases the effectiveness of dengue case surveillance to provide early
warning of building outbreaks. Our primary aim was to examine if mosquito-based
virological measures--monthly percentages of examined Ae. aegypti females
infected with DENV or examined homes from which at least one DENV-infected Ae.
aegypti female was collected--are correlated with reported dengue cases in the
same or subsequent months within study neighborhoods in Meida City, Mexico. The
study encompassed approximately 30 neighborhoods in the southern and eastern
parts of the city. Mosquitoes were collected monthly over a 15-mo period within
study homes (average of 145 homes examined per month); this produced
approximately 5,800 Ae. aegypti females subsequently examined for DENV RNA.
Although monthly dengue case numbers in the study neighborhoods varied > 100-fold
during the study period, we did not find statistically significant positive
correlations between monthly data for mosquito-based DENV surveillance measures
and reported dengue cases in the same or subsequent months. Monthly average
temperature, rainfall, and indoor abundance of Ae. aegypti females were
positively correlated (P < or = 0.001) with dengue case numbers in subsequent
months with lag times of 3-5, 2, and 1-2 mo, respectively. However, because
dengue outbreak risk is strongly influenced by serotype-specific susceptibility
of the human population to DENV, the value of weather conditions and
entomological indices to predict outbreaks is very limited. Potential ways to
improve the sensitivity of mosquito-based DENV surveillance are discussed.
PMID- 25118426
TI - Effects of azadirachtin on the biology of Lutzomyia longipalpis (Diptera:
Psychodidae: Phlebotominae) adult female, the main vector of American visceral
leishmaniasis.
AB - The effects of azadirachtin A added to the sucrose diet of the adult females on
the mortality, oviposition, and hatching of the sand fly vector of American
visceral leishmaniasis Lutzomyia longipalpis (Lutz & Neiva, 1912) were
investigated. Concentrations of 0.1, 1.0, and 10.0 microg/mg of azadirachtin
significantly increased insect mortality in comparison with control insects. The
same dose also significantly reduced oviposition but not hatching. After a long
development period, significantly fewer adult insects were obtained from eggs
hatching by azadirachtin-treated females in a dose-response manner. These results
indicate that azadirachtin is a potent sterilizer that could be used against the
development of Lu. longipalpis populations and as a tool for studying
physiological and biochemical processes in phlebotomine species.
PMID- 25118427
TI - Attractive toxic sugar baits mixed with pyriproxyfen sprayed on plants against
adult and larval Aedes albopictus (Diptera: Culicidae).
AB - The effect of spraying a mixture of the insect growth regulator (IGR)
pyriproxyfen (1 mg/liter) and either 1% boric acid sugar bait or eugenol sugar
bait on croton petra plants (Codiaeum variegatum L.) was evaluated against the
container-inhabiting mosquito, Aedes albopictus (Skuse). Treatments were applied
to plants and evaluated against adult and larval Ae. albopictus in the laboratory
through contact and wash off experiments, respectively. The control treatment
lacked an active ingredient and were treated with an attractive sugar bait. The
plants treated with attractive toxic sugar baits plus the IGR resulted in 60-100%
mortality of laboratory-reared adult Ae. albopictus. The pyriproxyfen solutions
collected from the plant wash experiment resulted in 80-100% emergence inhibition
to the exposed third- and fourth-instar larvae, compared with the untreated
control. Attractive toxic sugar baits mixed with the IGR not only provide
effective control of adult mosquitoes, but also provide additional control of
larval mosquitoes after being washed off from the treated plants.
PMID- 25118428
TI - New strains of Culex flavivirus isolated in Argentina.
AB - Strains of Culex flavivirus (CxFV), an insect virus isolated initially from
Japan, were isolated from different species of Culex sp. mosquitoes collected in
Corrientes province, Argentina, during 2009. CxFV was detected by reverse
transcription polymerase chain reaction and by isolation in C6/36 cell culture.
Phylogenetic analysis of nucleotide sequences showed that these strains are
related closely to a CxFV strain isolated from Trinidad. Our study represents the
first report of CxFV isolation and characterization in Argentina from the same
geographic area where West Nile Virus has been detected. Further evaluation and
viral competition studies will be necessary to determine the impact of this
insect flavivirus on an infection caused by other pathogenic flaviviruses.
PMID- 25118429
TI - Peer Assistance Services.
PMID- 25118430
TI - Prescription drug abuse does not discriminate.
PMID- 25118431
TI - Marijuana legalization in Colorado: a nursing student's perspective.
PMID- 25118432
TI - Affordable care.
PMID- 25118433
TI - Annual address of the President of the State Medical Society of Wisconsin:
commercialism. 1914.
PMID- 25118434
TI - Pediatrician's passion evolves into center for childhood safety.
PMID- 25118435
TI - Data sharing needed to increase quality and decrease costs.
PMID- 25118436
TI - The Wisconsin Pharmacy Quality Collaborative--a team-based approach to optimizing
medication therapy outcomes.
AB - The Wisconsin Pharmacy Quality Collaborative is an initiative of the Pharmacy
Society of Wisconsin, which connects community pharmacists with patients,
physicians, and health plans to improve the quality and reduce the cost of
medication use across Wisconsin. In 2012, the Pharmacy Society of Wisconsin
received a $4.1 million Health Care Innovation Award from the Centers for
Medicare and Medicaid Services to expand the Wisconsin Pharmacy Quality
Collaborative statewide. The aims of the Health Care Innovation Award are to help
reduce health care costs in Wisconsin by over $20 million and improve health and
health outcomes during the 3-year project period. Methods include implementing a
redesign of community pharmacy practices and facilitating medication management
services, which include intervention-based services and comprehensive medication
review and assessment visits for eligible commercial and Wisconsin Medicaid
members. The goals of the project are to: (1) improve medication use among
participating patients; (2) improve patient safety; (3) reduce health care costs
for participating patients and payers; and (4) establish partnerships between
pharmacists and physicians to enhance health outcomes.
PMID- 25118437
TI - Ocular trauma resulting in enucleation: A 12-year experience from a large
regional institution.
AB - PURPOSE: To review the frequency and cause of traumatic enucleation at the
University of Wisconsin. METHODS: A 12-year retrospective chart review (2000
2012) from the University of Wisconsin Hospital and Clinics of patients who
underwent enucleation following ocular trauma with specimens submitted to the
University of Wisconsin Eye Pathology Laboratory. RESULTS: A total of 188 eyes
enucleated following ocular trauma were identified between 2000 and 2012. One
hundred eleven (59%) cases had an identifiable mechanism of injury recorded in
the medical record and were included in the final analysis. The overall median
patient age was 41 years with 83.8% male. Assault was the most common reason for
enucleation (n=30, 27.0%) of which 15 (13.5%) cases were related to gunshot
wounds. Other causes included outdoor or recreational activities (n = 20, 18.0%),
fall (n = 14, 12.6%), non-motor vehicle accidents (n = 6, 5.5%), motor vehicle
accidents (n = 15, 13.5%), work-related injury (n = 15, 13.5%), and sports
related injury (n = 11, 10%). CONCLUSION: Assault is the most common cause of
traumatic ocular injury leading to enucleation. Gunshot and stab wounds were
responsible for the majority of these cases. Men were much more likely to undergo
enucleation due to ocular trauma with the exception being that caused by falls,
where the rate was nearly equal between men and women.
PMID- 25118438
TI - The Wisconsin immunization registry experience: comparing real-time and batched
file submissions from health care providers.
AB - CONTEXT: The Wisconsin Immunization Registry is a confidential, web-based system
used since 1999 as a centralized repository of immunization information for
Wisconsin residents. OBJECTIVE: Provide evidence based on Registry experiences
with electronic data exchange, comparing the benefits and drawbacks of using the
Health Level 7 standard, including the option for real time data exchange vs the
flat file method. DESIGN: For data regarding vaccinations received by children
aged 4 months through 6 years with Wisconsin addresses that were submitted to the
Registry during 2010 and 2011, data timeliness (days from vaccine administration
to date information was received) and completeness (percentage of records
received that include core data elements for electronic storage) were compared by
file submission method. RESULTS: Data submitted using Health Level 7 were
substantially more timely than data submitted using the flat file method.
Additionally, data submitted using Health Level 7 were substantially more
complete for each of the core elements compared to flat file submission.
CONCLUSIONS: Health care organizations that submit electronic data to
immunization information systems should be aware that the technical decision to
use the Health Level 7 format, particularly if real-time data exchange is
employed, can result in more timely and accurate data. This will assist
clinicians in adhering to the Advisory Committee on Immunization Practices
schedule and reducing over-immunization.
PMID- 25118439
TI - A clinical, diagnostic, and ecologic perspective on human anaplasmosis in the
Upper Midwest.
AB - INTRODUCTION: Human anaplasmosis caused by the bacterial pathogen Anaplasma
phagocytophilum was first discovered in the Upper Midwest in 1990. Since that
time the number of cases in the region has steadily increased, such that today,
the pathogen rivals that of Lyme disease in causing human tick-borne-related
illness. OBJECTIVE: We provide an overview of the biology, clinical
characteristics, and epidemiology of the disease in the Upper Midwest and discuss
currently available diagnostic methods. FINDINGS: Rapid differentiation of
anaplasmosis from other acute febrile illnesses and targeted treatment are
important for preventing severe disease and potentially fatal outcomes in
infected individuals. Beyond blood smear analysis and serology, the development
of real-time polymerase chain reaction (PCR) assays for clinical use holds
promise in improving our ability to make rapid diagnoses and to differentiate A
phagocytophilum infections from those produced by closely related Ehrlichia
pathogens, which are also present in the region. CONCLUSION: Continuing expansion
of the range of the black-legged tick (Ixodes scapuloris), the principal vector
of the disease, into areas heavily populated or visited by humans in the region
likely will result in this pathogen becoming an even greater burden on human
health. Efforts are needed to better characterize the current geographic
distribution of human Anaplasma and Ehrlichia cases to identify emerging foci and
to better understand the enzootic cycles that maintain the pathogens in the
region. Improved diagnostics may assist with such efforts.
PMID- 25118440
TI - Idiopathic spontaneous rupture of an intercostal artery.
AB - Spontaneous rupture of an intercostal artery is exceptionally rare without an
inciting event such as trauma or nontraumatic arterial wall weakening. This
report details the diagnosis and treatment of a 47-year-old man who presented
with a spontaneous hemothorax from an intercostal artery. There are very few
reports in the literature documenting spontaneous intercostal artery rupture
without associated illness or injury.
PMID- 25118442
TI - Endowment transitions from grantmaker to changemaker.
PMID- 25118443
TI - Reach out or drop out.
PMID- 25118441
TI - A case of pityriasis amiantacea with rapid response to treatment.
AB - Pityriasis amiantacea is a rare cutaneous reaction pattern to various underlying
inflammatory diseases of the scalp. The clinical findings are very characteristic
but often under-recognized. This condition can lead to scarring alopecia, and can
be refractory to conservative treatment. It is therefore important to recognize
the condition so that appropriate treatment can be initiated promptly.
PMID- 25118445
TI - Just give me a flight plan. How to make IT purchasing more effective.
PMID- 25118444
TI - Effective IT purchasing. What top-of-line issues comprise, challenge effective
hardware, software purchasing?
PMID- 25118446
TI - Revisions to NPSG.15.02.01 on home oxygen use.
PMID- 25118447
TI - Revisions to National Patient Safety Goal on home oxygen use.
PMID- 25118448
TI - Accepted: Revised hospital and critical access hospital requirements to align
with CMS.
PMID- 25118449
TI - Joint Commission announces changes in addressing Life Safety Code deficiencies.
Effective July 1, 2014: modifications to processing PFIs and equivalencies.
PMID- 25118450
TI - Revised: "Human resources" chapter for behavioral health care.
PMID- 25118451
TI - Clarification: Joint Commission expecations during IQCP transition.
PMID- 25118452
TI - We must convey the message.
PMID- 25118453
TI - Be it resolved that the leadership of the MNA...will support Medicare for AII
without reservation...
PMID- 25118454
TI - Nursing's voice in politics: the ongoing relationship between NURSES and
LEGISLATORS.
PMID- 25118455
TI - APS leadership meets with NIGMS.
PMID- 25118456
TI - Association of Chairs of Departments of Physiology 2013 Survey Results.
PMID- 25118457
TI - AAMC Medical School Faculty Compensation Survey.
PMID- 25118458
TI - APS supports 75 undergraduate students to conduct physiology laboratory research.
PMID- 25118459
TI - Zucker reappointed editor of AJP - Heart and Circulatory Physiology.
PMID- 25118461
TI - APS urges OLAW to revise "significant changes" guidance.
PMID- 25118460
TI - NIH finalizes chimpanzee housing requirements.
PMID- 25118462
TI - NIH to require balanced sex representation in animal and cell studies.
PMID- 25118464
TI - Letter to Keneth Baldwin.
PMID- 25118463
TI - Following Faraday's footsteps: getting involved in science outreach.
PMID- 25118465
TI - Are you INVESTED in NCNA?
PMID- 25118466
TI - Legislative update: busy short session.
PMID- 25118467
TI - NCNA leadership academy 2014: retreat reflections on leadership.
PMID- 25118468
TI - Unexpected inspiration.
PMID- 25118469
TI - RIBN conference offered partners/students opportunities to engage.
PMID- 25118470
TI - Nursing in concert: 2014 ANA membership assembly.
PMID- 25118471
TI - NP history lesson.
PMID- 25118472
TI - In your corner.
PMID- 25118473
TI - Breast cancer--new aspects of tumor biology: are calcitriol and cyclooxygenase-2
possible targets for breast cancer?
AB - Up until now there have been many advances in treatment options for breast
cancers such as targeted therapies like monoclonal antibodies, tyrosine kinase
inhibitors, mTOR antagonists, and vaccines. Despite these advances, there are
still many more that warrant further exploration. Two of these targets might be
the cyclooxygenase-2 (COX-2), the key enzyme required to convert arachidonic acid
to prostaglandins, and calcitriol [1,25(OH)2D3] which is the biologically active
form of vitamin D. Both calcitriol and the inhibition of COX-2 have shown
antiproliferative and prodifferentiation, as well as pro-apoptotic effects in
different malignancies in vitro and in vivo, and the key prostaglandin catabolic
enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is known to have tumor
suppressor activity. Furthermore, the combination ofcalcitriol and nonsteroidal
anti-inflammatory drugs (NSAIDs), such as non-selective and selective COX-2
inhibitors, acting synergistically to achieve significant cell growth inhibition
in prostate cancer. Some epidemiological studies suggest that vitamin D confers a
moderate benefit against breast cancer while most epidemiological studies presume
that NSAIDs confer the same. Nevertheless there is growing body of evidence that
COX-2 expression is a fundamental step in breast cancer carcinogenesis. To date,
clinical trials have been conducted in patients with different malignancies using
treatment strategies including COX-2 inhibitors and calcitriol and are showing
partially encouraging results. The goal of this review is to shed light on the
association between the prostaglandin as well as vitamin D metabolism relating to
the incidence and therapy of breast cancers. Moreover, this review will also
highlight potential treatment options, as well as extract any existing
interactions between the two metabolisms.
PMID- 25118474
TI - Brain metastases from gestational trophoblastic neoplasia: review of pertinent
literature.
AB - Brain metastasis from gestational trophoblastic neoplasia (GTN) is rare with
about 222 cases documented in the literature and an incidence of about 11% in
living GTN patients. Brain metastasis from GTN was part of a disseminated disease
in 90% of patients, single metastases in the brain - 80% and located in the
cerebrum - 90%. Brain metastasis was the only manifestation of metastatic GTN in
11.3% of patients, appeared synchronously with metastatic GTN in other sites of
the body - 30.6% and was diagnosed from 0.3 to 60 months after diagnosis of
metastatic GTN in other sites (most often in the lung) - 58.1%. Overall, 83.9% of
patients with brain metastases from GTN had also lung metastases from GTN. Brain
metastases from GTN showed a greater tendency to be hemorrhagic compared to brain
metastases from other primaries. In patients with brain metastases from GTN, the
best outcome was achieved with multimodal therapy including craniotomy, whole
brain radiotherapy, and EP-EMA or EMA-CO chemotherapy. Nonetheless, brain
metastasis from GTN is a grave disease with a median survival time from diagnosis
of brain metastasis of about 12 months.
PMID- 25118476
TI - Fertility preservation in women with early stage cervical cancer. Review of the
literature.
AB - Within the last decades, the percentage of diagnosed cervical cancer in women of
reproductive age has increased. The possibility of diagnosing small cervical
tumors (< or = twocm) in childbearing age, can be explained due to the fact that
many women, are aware of the benefits of Pap smear or colposcopy examination.
Many demand a more conservative policy to handle such lesions in order to have an
uneventful pregnancy in the near future.
PMID- 25118475
TI - The importance of alpha/beta (alpha/13) interferon receptors and signaling
pathways for the treatment of cervical intraepithelial neoplasias.
AB - INTRODUCTION: Immunotherapies have been effective in treating various forms of
cancer, including cervical intraepithelial neoplasias (CINs) predominantly caused
by human papilloma virus (HPV). DEVELOPMENT: To establish persistent infections
in stratified epithelia, HPV induces proliferative lesions. Viral gene products
are able to change gene expression and cellular proteins. Interferons (IFNs) are
inducible glycoproteins that have immunomodulatory, antiviral, antiproliferative,
and antiangiogenic effects. In particular, interferon-alpha (IFN-alpha) has been
shown to inhibit the development and progression of cervical cancer. In this
review, actions of interferons alpha/beta (alpha/beta), including their receptors
and signaling pathways, are described, as well as their clinical importance in
the immune response against cervical lesions. CONCLUSION: The interaction of IFN
alpha/beta with its receptor results in a series of phosphorylation events. These
mechanisms can be ineffective in IFN response, then it can also compromise the
therapeutic effects of immunotherapy.
PMID- 25118477
TI - Relationship of human papilloma virus multiple genotype infection with patient's
age and type of cervical lesion.
AB - PURPOSE OF INVESTIGATION: To document the prevalence of infection by multiple
genotypes of the human papilloma virus (HPV) in patients with cervical pathology
in a study population, and to determine the relationship between multiple
genotype infection, age of the patient, and the type of cervical pathology.
MATERIALS AND METHODS: Prospective, cross-sectional descriptive study. A total of
1,007 patients were recruited among women seen at the cervical pathology clinic
of Sant Joan de Deu University Hospital in Barcelona (Spain) between January 2003
and March 2011. Statistical analyses were done with SPSS v.19 software.
Differences between groups were considered statistically significant atp < 0.05.
RESULTS: There was 28.3% of the women (286 cases) that were infected by multiple
HPV genotypes. The mean number of genotypes identified was 2.52 (range 2 to 8).
Mean age of the patients with multiple genotype infection was 32.31 years, and
mean age of the patients with single genotype infection was 37.27 years (p <
0.001). The prevalence of infection by multiple HPV genotypes was 28% in patients
with cervical intraepithelial neoplasia grade 1 (CIN 1) and 33% in patients with
grade CIN 2-3 lesions, and both prevalence rates were significantly higher than
in patients with carcinoma (20%) (p = 0.03). CONCLUSIONS: In the present study
population the authors found no evidence of higher prevalence of multiple HPV
genotype infection in women with carcinoma. Age of women with multiple infection
was lower than those with single infection.
PMID- 25118478
TI - Predictors of malignancy in endometrial polyps: a multi-institutional cohort
study.
AB - PURPOSE OF INVESTIGATION: The risk of endometrial cancer in women with
endometrial polyps (EPs) has been reported to vary between 0.3% and 4.8%. There
is a lack of data about the management of asymptomatic women with incidental
diagnosis of EPs. In the present study the authors correlated demographic and
clinical characteristics with histopathological features of the EPs
hysteroscopically removed. MATERIALS AND METHODS: An observational multi
institutional cohort study was conducted from February 2010 to December 2012 to
identify all the premenopausal and postmenopausal women consecutively undergoing
hysteroscopic polypectomy. The data of women were reviewed and clinical features
were related to histopathologic results. RESULTS: The patients recruited were
813. The mean age was 52.5 years (range 22-87). The results showed a correlation
between older age, high body mass index (BMI) and obesity, postmenopausal state,
abnormal uterine bleeding (AUB), hypertension, and risk of malignant EPs. On
multivariable analysis, the correlation remained only for age (OR 1.08, 95% CI
1.03 - 1.14) and AUB (OR 3.53, 95% CI 1.87 - 6.65). CONCLUSION: Older patients in
postmenopausal status with AUB, a high BMI, and hypertension are at higher risk
for premalignant and malignant polyps. In these patients a surgical approach
should be used, consisting in hysteroscopical removing of the polyp.
PMID- 25118479
TI - An in vivo model for the study of ovarian cancer and the persistence of
characteristic mutations in xenografts.
AB - OBJECTIVE: To identify factors affecting xenograft growth of epithelial ovarian
cancer (EOC) cells in nude mice and to detect characteristic mutations occurring
in the xenografts following serial passage. MATERIALS AND METHODS: A total of 64
human EOCs were subcutaneously inoculated in Balb/c nude mice in order to obtain
a series of xenografts. Whole-exome sequencing was analyzed with Agilent
SureSelect targeted enrichment capture system and Illumina Solexa Hiseq 2000
sequencing platform. Mutations were confirmed by comparison against the reference
genome build 37.3. RESULTS: The tumor take rate was 50% (32/64). TP53 mutation
was detected in nine often Type II tumors. BRAF and CTNNB1 were not mutated in
any of the samples, and PTEN mutation occurred in only one sample. The present
data indicate that advanced stage serous EOCs and early stage non-serous EOCs
were easy to grow in nude mice, and xenografts maintained the characteristic
mutations. CONCLUSIONS: Advanced stage serous EOCs and early stage non-serous
EOCs were easy to grow in nude mice, and xenografts maintained the characteristic
mutations. Xenografts in nude mice are useful in vivo models for the study of
human EOCs.
PMID- 25118480
TI - Toxicity of concurrent chemoradiotherapy for locally advanced cervical cancer.
AB - AIM OF THE STUDY: The analysis of acute and late toxicity of concurrent
chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC) based on
review of 120 patients treated in Centre of Oncology in Krakow between 2001 and
2007. MATERIALS AND METHODS: Medium age of the patients was 52 years (43-66).
Overall, 12 patients (10.0%) were in Stage IB2, 54 (45.0%) in Stage II, 43
(35.8%) in Stage III, and 11 (9.2%) in Stage IVA. Squamous cell carcinoma was
present in 114 (95.0%) patients. Well-differentiated (grade 1) tumour was found
in 39 (32.5%) patients, moderately differentiated (grade 2) in 41 (34.2%), and
poorly differentiated (grade 3) in 40 (33.3%). Karnofsky performance status score
was 70 in 72 (60.0%) patients, and 80-90 in 48 (40%). External radiation therapy
was delivered with high-energy six to 15 MV photon beams using four-field brick
technique. The total dose of 50 Gy was given in 25 fractions within five weeks
using standard fractionation. Concurrently with external radiotherapy, six cycles
of chemotherapy were administered to all the patients as an intravenous infusion
of once-weekly cisplatin 40 mg/m2. On completion of external beam radiotherapy,
low-dose rate brachytherapy with tandem and two colpostats was performed to
deliver the dose of 40 Gy to point A in two 20 Gy insertions at weekly intervals.
RESULTS: Of the 120 patients in the investigated group, 78 (65%) were disease
free for five years. Symptoms of acute treatment-related toxicity grade 3 or 4
(WHO) occurred in 21.6% of patients including leucopoenia in 7.5%. anaemia in
5.0%, nausea and vomiting in 3.3%, diarrhea in 5.0%, and urinary tract infection
in 0.8%. Full planned treatment (teleradiotherapy + chemotherapy + brachytherapy)
completed 78.3% of the group; full planned radiotherapy without full chemotherapy
completed 20% of the patients. Late treatment complications of grade 3 or 4 were
observed in two (1.6%) patients (narrowing of large intestine requiring surgery
and recto-vaginal fistula). CONCLUSIONS: In patients with LACC treated with CCRT,
the most frequent acute toxic effects include: haematological disorders
(leucopoenia, anaemia), gastrointestinal disorders (nausea and vomiting,
diarrhea), vulvo-vaginal disorders, and urinary tract infection. The most
frequent late toxic effects included: rectal bleeding, bowel complications
requiring surgery, stenosis or recto-vaginal fistula, and haematuria.
PMID- 25118481
TI - En-bloc pelvic resection with concomitant rectosigmoid colectomy and immediate
anastomosis as part of primary cytoreductive surgery for patients with advanced
ovarian cancer.
AB - OBJECTIVE: To assess the authors' experiences in en bloc pelvic resection with
concomitant rectosigmoid colectomy and primary anastomosis as a part of primary
cytoreductive surgery for patients with advanced ovarian cancer. MATERIALS AND
METHODS: Atotal of 22 patients with FIGO Stage IIB-IV epithelial ovarian cancer
who underwent en bloc pelvic resection with anastomosis were retrospectively
reviewed. Data analyses were carried out using SPSS 10.0 and descriptive
statistics, Kaplan-Meier survival curves, and Log Rank (Mantel-Cox) test were
used for statistical estimations. RESULTS: Median age was 58.8 years. FIGO stage
distribution of the patients was; one (4.5%) IIB, three (13.7%) IIC, three
(13.7%) IIIA, six (27.3%) IIIB, and nine (40.9%) IIIC. Median peritoneal cancer
index (PCI) was 8 (range 5-22) and optimal cytoreduction was achieved in 18
patients (81.8%) of whom 13 (59.1%) had no macroscopic residual disease (complete
cytoreduction). There was no perioperative mortality. A total of nine
complications occurred in seven (31.8%) patients. Anastomotic leakage was
observed in one (4.5%) patient. There was no re-laparotomy. Mean follow-up time
was 60 months. There were 15 (68.2%) recurrences of which 12 (80%) presented in
extra-pelvic localizations. Mean disease-free survival (DFS) and overall survival
(OVS) were estimated as 43.6 and 50.5 months, respectively. Patients with
complete cytoreduction had a better DFS (p = 0.006) and OVS (p = 0.003) than
those with incomplete cytoreduction. CONCLUSION: En bloc pelvic resection, as a
part of surgical cytoreduction, seems to be a safe and effective procedure in
many patients with advanced ovarian cancer if required. Despite relatively high
general complication rate, anastomosis-related morbidity of this procedure is low
as 0.8%. Nevertheless, surgical plan and perioperative care should be
personalized according to medical and surgical conditions of the patient.
PMID- 25118482
TI - Apparent diffusion coefficient on 3.0 Tesla magnetic resonance imaging and
prognostic factors in breast cancer.
AB - AIM: The aim of the study was to evaluate whether the apparent diffusion
coefficient (ADC) provided by 3.0 Tesla diffusion-weighted imaging (3T DWI)
varies with the prognostic factors Ki67 and grading in invasive breast cancer.
MATERIALS AND METHODS: Seventy-three patients with 75 invasive breast cancer
lesions who had undergone 3.0 Tesla magnetic resonance imaging (MRI) for local
staging were enrolled. All lesions were confirmed by histologic and
immunohistochemical analysis. MRI included both dynamic contrast-enhanced and DWI
sequences. ADC value was obtained for each lesion. Histologic tumor grade was
established according to the Nottingham Grading System (NGS), while Ki67
expression was evaluated by MM1 clone IgG1 mouse anti-human monoclonal antibody.
Patients were divided into the following groups: grade 1 (G1), grade 2 (G2),
grade 1 plus grade 2 (G1+G2) and grade 3 (G3), and low Ki67 (< or = 14%),
intermediate Ki67 (15%-30%), and high Ki67 (> or = 30%). ADC values were compared
with the G and Ki67 groups. Statistical comparison was carried out using the Mann
Whitney U and the Kruskal-Wallis H test. RESULTS: ADC values were significantly
higher in G3 than in G1+G2 tumors; no significant difference was observed when
G1, G2, and G3 were compared. There was no statistically significant correlation
between ADC values and Ki67 percentage (p > 0.05). DISCUSSION: ADC values
obtained on 3T DWI correlate with low (G1+G2) and high-grade (G3) invasive breast
carcinomas. CONCLUSION: ADC may be a helpful tool for identifying high-grade
invasive breast carcinoma.
PMID- 25118483
TI - Contrast-enhanced ultrasonography in diagnosis of benign and malignant breast
lesions.
AB - PURPOSE: This study aims to investigate the value of real-time contrast-enhanced
ultrasonography (US) in differentiating benign and malignant breast lumps.
MATERIALS AND METHODS: Patients with breast lesions were observed. The
enhancement form, intensity, and time-intensity curve were classified, and the
characteristics of all the lesions were analyzed. RESULTS: Inhomogeneous partial
enhancement and entire enhancement were exhibited in most of the malignant
lesions. High enhancements were observed in malignant lesions, whereas lower
enhancement and no enhancement were exhibited in the benign tumors. The peak
value and regression time were significantly different between the two groups.
CONCLUSION: There's a significant difference regarding the results of real-time
contrast-enhanced ultrasound between the benign tumor and malignant tumor which
would help to improve the diagnostic accuracy of breast neoplasms.
PMID- 25118485
TI - Prognostic factors affecting lymph node involvement in cervical cancer.
AB - AIM: Clinical and histopathological factors that affect lymph node involvement in
cervical cancer and the prognostic importance of these factors were evaluated in
this study. MATERIALS AND METHODS: A total of 179 patients were diagnosed with
cervical cancer between January 2001 and June 2010 and were included in this
study. The patients' charts were evaluated retrospectively and information was
collected by reaching 89 patients and asking questions. RESULTS: When the
prognostic factors that affect pelvic lymph node involvement were evaluated,
increased tumor size and increased invasion depth, presence of lymphovascular
area involvement, and an advanced stage were observed to statistically
significantly increase pelvic lymph node involvement. No relationship was found
between tumor histology and grade; parametrial, endometrial, vaginal involvement,
and pelvic lymph node involvement. CONCLUSION: Knowledge of prognostic factors in
cervical cancer plays an important role in determining the morbidity and
mortality and the treatment strategies.
PMID- 25118484
TI - Comparison of pelvic masses score (PMS) and Risk of Malignancy Index (RMI 3) in
the evaluation of pelvic masses.
AB - PURPOSE: Ovarian cancer is the fourth cause of death from cancer in women
worldwide and the majority of its diagnoses is made in an advanced stage of the
disease. Several sonographic scoring systems have been created for a better
preoperative discrimination between benign and malignant pelvic masses. The aim
of this study was to evaluate the performances of the Risk of the Malignancy
Index 3 (RMI 3) and the Pelvic Masses Score (PMS). MATERIALS AND METHODS: This
retrospective study was performed in 55 women admitted to the department of
Obstetrics and Gynecology of University of Udine for surgical exploration of
pelvic masses between 2009 and 2012. Sensitivity, specificity, positive
predictive value (PPV) and negative predictive value (NPV) were calculated for
both the scores. RESULTS: PMS showed a sensitivity of 100%, a specificity of
93.8%, a PPV of 70%, and a NPV of 100%, while RMI 3 yielded a sensitivity of 85%,
a specificity of 91%, a PPV of 60%, and a NPV of 97.8%. CONCLUSION: The authors
found that, in discriminating between benign and malignant pelvic disease, the
PMS method was more reliable than RMI3. PMS is a simple scoring system which can
be used in clinical practice.
PMID- 25118486
TI - A survey of Jordanian obstetricians and gynecologists' knowledge and attitudes
toward human papillomavirus infection and vaccination.
AB - OBJECTIVE: To assess the knowledge and attitudes of Jordanian obstetricians and
gynecologists toward human papillomavirus (HPV) infection and its vaccine.
MATERIALS AND METHODS: A self-administered, anonymous questionnaire was
distributed to 400 participants attending scientific meetings. The survey focused
on three areas: knowledge of HPV infection, vaccine, and attitude toward
vaccination of female adolescents. RESULTS: Survey response rate was of 72.3%.
The vast majority knew most of the statements related to knowledge of HPV
infection, 66% thought that conventional screening Pap test have a sensitivity of
> 75%, and only 44% of them knew that there are 13 to 17 HPV types that cause
cervical cancer. The majority of the respondents (79%) knew that the vaccine
would lead to long lasting immunity and 45% of the respondents thought that the
vaccination would eliminate the need for regular Pap test. The majority (78%)
indicated that the vaccine should be given to girls before the beginning of
sexually active life. Overall, 67.5% of respondents intend to prescribe HPV
vaccines and 79.6% of the respondents intend to recommend the vaccine if it is
publicly funded. CONCLUSION: Most of the gynecologists in Jordan have the
intention to recommend HPV vaccine, the deficit in their knowledge of HPV
infection and vaccine must be corrected to assure acceptability of the vaccine.
PMID- 25118487
TI - Curcumin induces human SKOV3 cell apoptosis via the activation of Rho-kinase.
AB - OBJECTIVE: Curcumin has been showed anti-inflammation and anti-cancer effect in
various cancer cells such as lung cancer, breast cancer, and so on. However the
pro-apoptosis effect and the mechanism of curcumin in ovarian cell is still not
very clear. In this study, the authors demonstrated that curcumin induced human
SKOV3 cell apoptosis and explored the underlying mechanism concerning Rho A/Rho
kinase pathway. MATERIALS AND METHODS: Human SKOV3 cell was performed with MTT
assay to measure the cell viability with curcumin. The cell was treatment with 15
microM or 30 microM curcumin and flow cytometry. Cell apoptosis analysis was
performed to measure the cell apoptosis level. In order to explore the mechanism
concerning pro-apoptosis activity of curcumin, the cells were pre-treatment with
Y-27632, a specific Rho-kinase inhibitor, before curcumin was added. Then the
expression of activated caspase-3 and Rho A, Rho-kinase was detected by western
blot. RESULTS: Treatment with 15 microM or 30 microM curcumin significantly
promoted the apoptosis of SKOV3 cell (p < 0.05) and the apoptosis rate is dose
dependent. Curcumin also activated the expression of Rho A and Rho-kinase in a
dose-dependent effect. When pre-treatment with Y-27632, the expression of
activated caspase-3 was significantly decreased compared to the group without Y
27632 pre-treatment (p < 0.05). CONCLUSIONS: Curcumin induced human SKOV3 cell
apoptosis in a dose-dependent effect. The pro-apoptosis effect of curcumin is
partly mediated via the activation of Rho A/Rho-kinase signal pathway. This may
help to further clarify the mechanisms of curcumin in ovarian cancer therapy.
PMID- 25118488
TI - Is HE4 a useful endometrioma marker?
AB - PURPOSE OF INVESTIGATION: By the comparison between most used tumor marker trend
(cancer antigen 125: CA 125 and human epididymal secretory protein E4: HE4)
before and after laparoscopic surgery, the aim of the present study was to assess
HE4 usefulness in ovarian benign cyst and endometrioma diagnosis. MATERIALS AND
METHODS: Thirty-eight patients were enrolled in this prospective study: 25 women
underwent unilateral endometriosis ovarian cyst excision, 13 underwent benign
ovarian cyst incision, and 26 were healthy controls. CA 125 and HE4 serum levels
were estimated before surgery (in the early proliferative phase of the cycle) and
one month after surgery. RESULTS: A statistically significant decrease of CA 125
serum level was found after an endometrioma surgical excision but no decreases in
HE4 serum level. CONCLUSION: In patients with endometrioma, no alteration was
found in HE4 serum levels before and after surgery, while CA125 serum levels
decreased after surgery. HE4 may better distinguish a malign cyst from benign
one, but it is not useful in the diagnosis of low risk endometrioma.
PMID- 25118489
TI - Therapy-related myelodysplastic syndrome and acute myeloid leukemia following
chemotherapy (paclitaxel and carboplatin) and radiation therapy in ovarian
cancer: a case report.
AB - In recent years, the incidence of therapy-related myelodysplastic syndrome (t
MDS) and therapy-related acute myeloid leukemia (t-AML) that occur during
chemotherapy for ovarian cancer has increased. While alkylating agents and
topoisomerase II inhibitors are particularly mutagenic and have strong
leukemogenic potential, paclitaxel and combination chemotherapy/radiation therapy
also appear to induce t-MDS. The present authors report a case of t-MDS that
developed during chemotherapy and radiation therapy for ovarian cancer. The
patient was a 75-year-old woman who received six courses of
cyclophosphamide/doxorubicin/cisplatin (CAP) therapy after initial surgery for
Stage IIIc grade ovarian cancer in 1995. Beginning in February 2005, the patient
experienced multiple recurrences due to sternal metastasis. Chemotherapy,
including paclitaxel and carboplatin (TC), was administered intermittently and
was combined with radiation therapy to a sternal metastatic lesion. Pancytopenia
was observed in December 2008, and she was diagnosed with t-MDS (WHO subtype,
refractory cytopenias with multilineage dysplasia [RCMD]): the time from first
chemotherapy to t-MDS onset was 106 months. Without evidence of blast crisis, the
recurrent lesions continued to grow and caused multiple cerebral infarctions,
from which she eventually died. The cumulative doses of paclitaxel and
carboplatin administered to this patient were 1,968 mg and 6,480 mg,
respectively.
PMID- 25118490
TI - Rectus abdominis muscle resection and fascial reconstruction for the treatment of
uterine leiomyosarcoma invading the abdominal wall: a case report.
AB - The authors present a case of intra-abdominal recurrent leiomyosarcoma invading a
large area of the abdominal wall. The patient underwent cytoreductive surgery,
including resection of the rectus abdominis muscle, followed by reconstruction of
the defect using synthetic mesh. The tumor was surgically removed by en bloc
resection, including most of the rectus abdominis muscle and ileum. The abdominal
wall defect was repaired using synthetic mesh. The patient underwent radiotherapy
and chemotherapy after the surgery and was healthy one year later.
PMID- 25118491
TI - A case of accessory mammary cancer in a male patient and a literature review.
AB - A 68-year-old Chinese male patient was referred to the present hospital because
of a right axillary lump in May 2011. Physical examination showed a rigid movable
mass measuring 35 mm in diameter in the right axilla. No mass was palpable in
either breast. Mammograms were normal. Physical and imaging examination of the
head and neck region, lung, and upper and lower gastrointestinal tract also
revealed no evidence of a primary tumor. Ultrasonography and resonance imaging
(MRI) revealed no evidence of tumors in the bilateral mammary glands. Fine needle
histological biopsy for suspected malignancy was performed, and the patient
underwent tumor resection with axillary lymph node dissection on Jun 2011.
Moderately differentiated adenocarcinoma in ectopic breast tissue was diagnosed
based on the pathologic result, the tumor was immunohistochemically positive for
ER, PR, and HER-2.
PMID- 25118492
TI - Successful treatment of a large symptomatic lymphocyst with percutaneus drainage
and repeated iodopovidone sclerotherapy.
AB - The objective of the case report was to present an easy and safe method for
treatment of a large, persistent lymphocyst, through a procedure performed in an
ambulatory setting. The patient diagnosed with large (1,800 mi), symptomatic
(pains, renal insufficiency) lymphocyst after lymphadenectomy for cervical
cancer, was successfully treated with percutaneous drainage (using vascular
drains) and five sessions of sclerotherapy with 10% iodopovidone, performed in
ambulatory settings. The method was minimally invasive, safe, and effective in
management of symptomatic lymphocyst.
PMID- 25118493
TI - Heterologous type of malignant mixed Mullerian tumor of the uterus presenting as
a vulvar mass.
AB - Carcinosarcoma is a rare, extremely aggressive tumor of the uterus with a poor
prognosis. The authors describe a case of a 78-year-old woman who presented with
a giant mass protruding through the cervix, vagina, and vulva. A total abdominal
hysterectomy with bilateral salpingo-oophorectomy was performed. The
histopathological examination of the surgical specimen revealed a malignant mixed
Mullerian tumor. The clinical and pathological features, molecular data, and
prognosis of this aggressive neoplasm are discussed. Although uterine
carcinosarcomas are extremely rare, when a postmenopausal woman with a vulvar
mass is admitted to the gynecology clinic, the physician should consider that the
mass may be a carcinosarcoma.
PMID- 25118494
TI - Uterine endometrial carcinoma with trophoblastic differentiation: a case report
with literature review.
AB - Choriocarcinoma is categorized as either gestational or nongestational depending
on its origin. Nongestational choriocarcinoma originated in the trophoblastic
differentiation is a rare but an aggressive tumor. This article reports a
nongestational case of a uterine endometrial carcinoma with trophoblastic
differentiation. A 54-year-old woman with a history of atypical genital bleeding
that underwent semi-radical hysterectomy, bilateral salpingo-oophrectomy, and
pelvic lymph nodes dissection. Pathological investigation showed that the tumor
had endometrioid adenocarcinoma and choriocarcinomatous components. Although a
series of multimodality treatments including craniotomy were performed, she died
of aggressive lung and brain metastases one year after the primary surgery.
PMID- 25118495
TI - Aggressive angiomyxoma of the female genital tract: report of two cases.
AB - Aggressive angiomyxoma (AA) was identified in 1983 and 250 cases of this rare
tumor have since been reported in the literature. It is characterized by a
locally infiltrative and recurrent nature; however, it rarely shows distant
metastasis. Surgical managements can successfully treat AA patients but may
result in a significant morbidity due to the large size and infiltration of the
tumor. Less radical surgeries have recently been recommended in the treatment of
this tumor, but adjuvant therapies have not yet been fully established. The
authors report here two AA cases that were treated at their hospital, with a
brief review of the literature.
PMID- 25118496
TI - Rupture of an endometrioma with extremely high serum CA-125 level (> 10,000
IU/ml) and ascites resembling ovarian cancer.
AB - Carbohydate antigen 125 (CA-125) is a type of cell surface glycoproteins present
in more than 80% of non-mucinous epithelial ovarian carcinomas; however, benign
gynecologic conditions commonly cause a smaller increase in CA-125 level. This
report presents the details regarding a 44-year-old woman with extremely high
serum CA-125 level and ascites. She complained of having abdominal pain and
abdominal distension. Her serum CA-125 level had been markedly elevated (> 10,000
IU!ml) and computed tomograpgy (CT) revealed an ovarian tumor and massive
ascites. The cytological analysis showed no evidence of malignancy, however, the
positron emission CT (PET-CT) scan suggested ovarian malignancy with peritoneal
carcinomatosis. Under the impression that the patient had ovarian cancer, the
present surgical team carried out an explorative laparotomy and discovered the
ruptured bilateral ovarian endometriomas. In this study, it is suggested that
clinicians carrying out differential diagnosis of pelvic mass with high serum CA
125 level and ascites should consider not only ovarian cancer but also ruptured
endometrioma.
PMID- 25118497
TI - Adenosarcoma of the uterine body initially presenting as an interstitial small
tumor of the uterus: a case report.
AB - Adenosarcoma of the uterine body is a rare mixed tumor in which a benign
epithelial component is mixed with a malignant stromal element. It has been
considered that this tumor originates from the endometrium and its most common
finding of imaging is a polypoid tumor occupying the uterine cavity. The authors
herein present a case of 37-year-old female with a complaint of abnormal vaginal
bleeding. At the first visit, transvaginal ultrasound and magnetic resonance
imaging (MRI) showed a round mass with a diameter of one cm in the uterine wall.
No malignant pathological finding was detected. The patient visited the authors
again one year later, because of continuous bleeding. At that time, they found a
polypoid tumor in the uterine cavity, which turned out to be adenosarcoma with
sarcomatous overgrowth. The round mass in the uterus detected at first time seems
to have been incipience of adenosarcoma. Prodromal sign of adenosarcoma has not
been reported previously.
PMID- 25118498
TI - Reference values for placental growth factor (PlGF) concentration and uterine
artery doppler pulsatility index (PI) at 11-13(+6) weeks of gestation in the
Polish population.
AB - OBJECTIVES: The aim of the study was to determine placental growth factor (PIGF)
concentration and uterine artery (UtA) Doppler pulsatility index (PI) at 11
13(+6) weeks of gestation in the Polish population. MATERIAL AND METHODS: A
prospective study was performed in pregnant women who underwent routine
ultrasound scan at 11-13(+6) weeks of gestation. All participants completed a
questionnaire about their medical history demographics and current pregnancy.
Mean arterial pressure (MAP) was calculated. Gestational age was confirmed by CRL
and mean UtA PI was calculated. Blood samples were taken to measure beta HCG,
PAPP-A and P/GF concentrations. RESULTS: Out of the 577 analyzed participants, 60
(10.4%) were found to have abnormal placentation disorders (20 -hypertensive
disorders and 40-IUGR). The patients were subdivided into two groups, depending
on pregnancy outcome: unaffected (n = 517) and affected (n = 60). The study did
not confirm the anticipated correlation between maternal BMI and PIGF, but the
concentration of PIGF was significantly increased in smokers. UtA PI values were
not statistically significantly different depending on maternal age, BMI, method
of conception, smoking or parity The study confirms that both, UtA PI and PIGF
concentrations are CRL-dependent. Median MoM values for PIGF and UtA PI were
obtained for each set of CRL measurements. Median PIGF MoM was decreased in
pregnancies complicated by hypertensive disorders and IUGR as compared to the
unaffected group. CONCLUSIONS: The established reference ranges for UtA PI and
PIGF at 11-13(+6) weeks of gestation may be of clinical value in predicting
placenta-associated diseases in early stages of pregnancy in the Polish
population.
PMID- 25118499
TI - The role of 401a>G polymorphism of methylenetetrahydrofolate dehydrogenase gene
(MTHFD1) in fetal hypotrophy.
AB - INTRODUCTION: Important role is attributed to genetic polymorphisms influencing
enzymatic activity in folate metabolism. These inherited genetic variants may
influence fetal growth and fetal hypotrophy development. The aim of the study was
to investigate the connection of 401A>G polymorphism of methyleneterahydrofolate
dehydrogenase gene (MTHFD1) with increased risk of fetal hypotrophy. MATERIAL AND
METHODS: To the study group 120 women who delivered children with fetal
hypotrophy and to the control group 120 healthy women were enrolled. Study group
was divided into subgroups according to gestational age at delivery (52 patients
< 37 weeks, 68 patients > or = 37 weeks) and to the neonatal weight (31 mothers
of newborns with birth weight < 1500 g, 89 mothers of newborns with birth weight
> or = 1500 g). The genetic analysis was performed with the use of PCR/RFLP
method. RESULTS: We observed statistically higher occurrence of mutated 401A
allele in hypotrophy group (401A: 27,1 vs. 18,8%, OR = 1,61, p = 0,02). At
mothers who delivered hypotrophic children weighted more than 1500 g the presence
of 401A allele was higher (28,7 vs. 18,8%, OR = 1,74, p = 0,01). Additionally in
mothers who delivered hypotrophic children before 37 gestational week
statistically higher frequency of 401A allele has been noted (31,7 vs. 18,8%, OR
= 2,01, p = 0,007). CONCLUSIONS: Our results indicated that mutated 401A allele
of MTHFD1 gene is essential risk factor of fetal hypotrophy in population of
Polish women. Appropriate folate supplementation could be particularly essential
in women carriers the genetic polymorphism influencing the folate metabolism.
PMID- 25118500
TI - Comparison of maternal and fetal blood levels of caffeine and its metabolite. A
pilot study.
AB - OBJECTIVE: The aim of the study was to compare caffeine and paraxanthine
concentrations in venous blood of pregnant women and in the umbilical cord blood
of their newborns. MATERIALS AND METHODS: Pregnant women who gave birth at the
Clinic of Obstetrics, Gynecology and Oncology 2nd Faculty of Medicine, Medical
University of Warsaw were included in the study Caffeine and paraxanthine
concentrations were analyzed in 30 samples of venous blood serum drawn from the
women before delivery and 30 samples of umbilical cord blood serum of their
newborns. Caffeine intake in the last 24 hours before delivery was estimated
using a questionnaire. Statistical analysis employed a linear logistic regression
model, Wilcoxon rank sum test and a non-parametric Spearman's rank correlation
coefficient. RESULTS: No difference was found between caffeine concentration in
maternal venous blood and neonatal umbilical cord blood. However; paraxanthine
level in venous blood was higher than in umbilical cord blood (p = 0.04).
CONCLUSIONS: Caffeine consumed by a pregnant woman passes through the placenta to
the fetus freely.
PMID- 25118501
TI - [Results of Doppler examinations in fetuses of mothers with early- and late-onset
preeclampsia].
AB - OBJECTIVES: Comparison of fetal umbilical and middle cerebral artery flow between
early- and late-onset preeclampsia. MATERIAL AND METHODS: Our study was conducted
among 50 patients with preeclampsia in the third trimester of pregnancy and
included 30 women with early-onset and 20 with late-onset disease. Early-onset
preeclampsia (EOP) and late-onset preeclampsia (LOP) were defined as onset of the
disease before and after 34 weeks of gestation, respectively Doppler examinations
of the fetal umbilical and middle cerebral artery were performed in all patients.
Pulsatility Index (PI) and cerebral-umbilical ratio (CUR) were measured each
time. RESULTS: Mean value of the umbilical artery PI was significantly higher in
fetuses of patients with EOP in comparison to LOF, whereas mean PI value in MCA
was significantly lower in fetuses from the group with EOP than LOP The
percentage of abnormal results of fetal Doppler examinations, both in the
umbilical artery and middle cerebral artery was significantly higher in EOP than
in LOP. The same tendency was observed for CUR. CONCLUSIONS: 1. Early-onset
preeclampsia is characterized by significantly higher degree of placental
insufficiency than late-onset disease. 2. The obtained results indicate a
significant, pathological role of the placenta in early-onset preeclampsia. 3.
Pathophysiological differences between early- and late-onset preeclampsia lead to
different clinical approach to patients, depending on the type of the disease,
including emphasis on Doppler examination in the early-onset preeclampsia. 4. The
presence or absence of placental insufficiency in pregnancy complicated by
preeclampsia seems to determine the clinical course of the disease, thus allowing
for an alternative classification of the condition into placental and maternal
preeclampsia.
PMID- 25118502
TI - Retrograde diastolic blood flow in the aortic isthmus is not a simple marker of
abnormal fetal outcome in pregnancy complicated by IUGR--a pilot study.
AB - AIM: To evaluate the relation between retrograde diastolic blood flow in the
aortic isthmus and adverse perinatal outcome in fetuses with IUGR. MATERIALS AND
METHODS: The study included 33 fetuses with IUGR defined as the estimated fetal
weight and abdominal circumference under the 10th percentile for a given
gestational age. The Doppler examination of the blood flow in the aortic isthmus,
umbilical artery umbilical vein, middle cerebral artery uterine arteries and
ductus venosus was performed regularly The study population was further divided
into two subgroups, depending on the aortic isthmus blood flow direction, i.e.
with and without retrograde isthmic diastolic flow. Furthermore, the relation
between Doppler blood flow parameters and determinants of the perinatal outcome
was analyzed. The perinatal outcome was reported as adverse if any of the
following occurred: umbilical cord blood pH < 7,2; 5-minute Apgar score < 7;
respiratory distress syndrome, intraventricular hemorrhage (/ll/IV grade);
necrotizing enterocolitis; sepsis; intrauterine or neonatal death. RESULTS: There
was no statistically significant difference in the incidence of adverse perinatal
outcome between the antegrade and retrograde isthmic blood flow groups. Moreover;
the study showed no statistically significant relationship between the retrograde
blood flow in the aortic isthmus and the prevalence of abnormal flow in the
analyzed vessels. CONCLUSION: Retrograde diastolic blood flow in the aortic
isthmus presents a low sensitivity and low predictive value in predicting the
adverse perinatal outcome in pregnancies complicated with IUGR.
PMID- 25118503
TI - Maternal serum amyloid A levels in pregnancies complicated with preterm prelabour
rupture of membranes.
AB - OBJECTIVE: The aim of the study was to investigate a possible association between
maternal serum amyloid A levels (SAA) and maternal and fetal parameters in
pregnancies complicated with preterm prelabor rupture of membranes (PPROM).
MATERIAL AND METHODS: A total of 88 pregnant women (PPROM group, n = 44 and
control group, n = 44) were included into this prospective case control study
Serum blood samples for SAA were obtained from both groups within 1 h since the
rupture of the membranes and before administration of any medicine. The samples
were kept frozen at -70 degrees C until the analysis. The recorded risk factors
were: age, gravidity parity delivery mode, gender; fetal birth weight, APGAR
scores, white blood cell count, microCRRF neutrophil/lymphocyte ratio (NLR), and
maternal serum SAA levels. RESULTS: Demographic characteristics showed no
statistically significant differences between the groups (p > 0.05). The mode of
delivery mode was cesarean section: 41% and 43.2% in the study and the control
group, respectively and this difference was statistically significant between the
groups (p < 0.05). Fetal parameters also showed statistically significant
differences (p < 0.05). There was a statistically significant difference between
the groups in terms of micro CRP NLR and SAA. SAA levels were higher in the PPROM
group (p < 0.005). SAA levels at a cut-off 95.63 ng/ml. CONCLUSION: We are of the
opinion that second trimester maternal serum SAA level may be a predictive marker
for PPROM. However further studies with more participants are required.
PMID- 25118504
TI - [Effects of metformin on the survival of the SKOV-3 ovarian cancer cell line and
the expression of genes encoding enzymes involved in O-Glcnacylation].
AB - OBJECTIVES: The aim of the study was to evaluate the cytotoxic effect of
metformin on the ovarian cancer cells SKOV-3 and analyze the impact of this
compound on the expression of genes coding for O-GlcNAc cycling enzymes, i.e. O
GlcNAc transferase (OGT) and -N-acetylglucosaminidase (OGA). MATERIALS AND
METHODS: Viability and proliferation of control cells and cells treated with
metformin were evaluated by MTT test and trypan blue staining. OGT and OGA mRNA
expressions analysis was performed using real-time PCR method. RESULTS: A
metformin concentration-dependent decrease of SKOV-3 cell viability was observed.
The IC50 parameter for metformin cytotoxicity was 14 mM. The SKOV-3 cell doubling
time was 45 hours. The cell population treated with 10 mM metformin did not
double even after 72 hours. There was no significant difference in mRNA level of
OGA between control cells and cells treated with metformin. The OGT mRNA level
was significantly higher in cells treated with metforrhin for 24 hours as
compared to the control cells. The increase of OGT mRNA was dependent on time of
incubation. Cells treated with metformin for 48 hour showed higher expression of
OGT than cells treated for 24 hours. CONCLUSION: Antiproliferative activity of
metformin suggests that this compound may be considered as a candidate for
potential chemotherapeutic agent. However taking into account its impact on the
expression of O-GlcNAc transferase, further studies on the molecular mechanism of
metformin action are necessary
PMID- 25118505
TI - [Metformin in pregnancy].
AB - Metformin is an oral insulin-sensitizing anti-diabetic drug. Polycystic ovary
syndrome (PCOS) and gestational diabetes (GDM) are both associated with insulin
resistance and hyperinsulinemia. Metformin can bring potential benefits in
pregnant women due to its favorable metabolic effect. Nevertheless, there is a
possibility of adverse effects on the fetus as metformin crosses the placenta. In
this review we discuss safety and indications for metformin administration in
pregnancy.
PMID- 25118506
TI - [Fetal hepatic artery flow assessment in prenatal diagnostics--a review of the
literature].
AB - Standards of screening tests for the most frequent fetal chromosomal defects in
modern non-invasive prenatal diagnostics provide sensitivity of about 93-96%,
with the false positive rate of 2.5%. During the first trimester scan, routinely
performed between 11 and 13+6 week of pregnancy the calculation of the risk for
chromosomal aberrations is based on maternal age (MA), nuchal translucency (NT),
levels of free beta human chorionic gonadotropin (free beta-hCG), pregnancy
associated plasma protein A (PAPP-A) in maternal blood, as well as the parameters
from extended ultrasound examination like evaluation of the nasal bone (NB),
blood flow in ductus venosus (DV), visualization of the tricuspid valve with
potential regurgitation (TR) or measurement of the frontomaxillary facial angle
(FMFA). The 100% detection rate remains unachievable at present, despite
constantly improving guidelines for specialists, quality of imaging, and
advancement in ultrasound technology Therefore, several studies have been
undertaken to establish the group of 'additional markers' of chromosomal defects
which, when combined with basic markers of routine screening tests, might
increase the detection rate and approach it to 100%. Results of recent studies
imply that evaluation of blood flow in fetal hepatic artery performed during the
first trimester scan may become a new additional marker for chromosomal defects.
PMID- 25118507
TI - Complications of sub-urethral sling procedures.
AB - Approximately one-third of the female population has been estimated to suffer
from stress urinary incontinence. Surgical management of this disorder has been
an area of ongoing innovation since the beginning of the 20th century. Better
understanding of the underlying patomechanisms resulted in the invention of
suburethral sling, that proved to be very effective in terms of the cure rates.
The introduction of sling techniques also caused a considerable reduction of the
rates of intra- and postoperative complications of incontinence treatment.
Unfortunately modern anti-incontinence surgery continues to be associated with a
high risk of both, perioperative morbidity and long-term adverse outcomes, even
with the recently introduced single-incision techniques. The article focuses on
intra- and postoperative complications of sling techniques in anti-incontinence
surgery. Both, common and rare adverse outcomes are widely discussed.
PMID- 25118509
TI - [Krukenberg tumor--a multidisciplinary approach--a case report].
AB - Metastatic lesions within the ovary constitute a serious diagnostic problem in
daily practice. We present an interesting case of Krukenberg tumor in a woman 13
years after partial gastrectomy due to stomach cancer. Our case confirms that
every woman with history of cancer should remain under gynecological control. It
is important due to a high risk of metastatic changes localized in the ovaries,
regardless of the time elapsed since the diagnosis of the primary tumor
PMID- 25118508
TI - Prenatal diagnosis of craniosynostosis (compound Saethre-Chotzen syndrome
phenotype) caused by a de novo complex chromosomal rearrangement (1; 4; 7) with a
microdeletion of 7p21.3-7p15.3, including TWIST1 gene--a case report.
AB - Craniosynostosis (a premature fusion of the cranial sutures) occurs with a
frequency of 1 in 2100-2500 births and in over 40% cases is caused by known
genetic factors--either single gene mutations or chromosomal rearrangements.
Cases caused by complex chromosomal abnormalities are uncommon and likely
associated with compound phenotype. Saethre-Chotzen syndrome (SCS) [#101400] is
caused by TWIST1 gene haploinsufficiency. Its phenotype includes uni- or
bicoronal synostosis, short stature, facial dysmorphism and variable anomalies of
the hands and feet. Due to its poor sonographic manifestation a prenatal
diagnosis of SCS is challenging. We report a case of a prenatally detected
craniosynostosis (compound Saethre-Chotzen syndrome phenotype) caused by a de
novo complex chromosomal rearrangement (1; 4; 7) with a microdeletion of 7p21.3
7p15.3, including TWIST1 gene.
PMID- 25118510
TI - [Assisted reproductive medicine in Poland, 2011--SPiN PTG report].
AB - AIM: The aim of this report is to present data concerning results and
complications related to infertility treatment using assisted reproductive
technology (ART) and insemination (IUI) in Poland in 2011. MATERIALS AND METHODS:
The report was prepared by the Fertility and Sterility Special Interest Group of
the Polish Gynaecological Society (SPiN PTG), based on individual data provided
by fertility clinics in Poland. Reporting was voluntary and the provided data was
not subject to external control. The report presents the availability and the
structure of infertility treatment services, the number of procedures performed,
their effectiveness and the most common complications. MAIN RESULTS: In 2013, 33
Polish fertility clinics provided information to the SPiN PTG report, presenting
data from the year 2011. The total number of reported treatment cycles using ART
was 15,340 (incl. 10,011 IVF/ICSI procedures) and 15,627 IUI procedures. The rate
of clinical pregnancies in terms of a cycle was 34.2% in case of IVF/ ICSI
procedures and 13.4% in case of IUI. The prevalence of multiple births was 20.2%
and 8.3% respectively in case of IVF/ICSI and IUI methods. The most frequent
complication in the course of treatment using ART was ovarian hyperstimulation
syndrome (OHSS). CONCLUSION: The SPiN PTG report allows to find out the average
effectiveness and safety of assisted reproduction technologies and is currently
the only proof of responsibility and due diligence of fertility centres in
Poland. However due to the lack of a central register of fertility clinics,
facultative participation in the report as well as incomplete information on
pregnancy and delivery the collected data does not reflect the full spectrum of
the Polish reproductive medicine.
PMID- 25118511
TI - [Recommendations of the Polish Gynecological Society concerning application of
GINEintima products in gynecology].
PMID- 25118512
TI - An examination of assessment arrangements and service use for older people in
receipt of care management.
AB - With anticipated greater demand for formal care services globally, this article
examines the sociodemographic and health characteristics of frail older people in
receipt of community support. Data were collected from audits of case files of
older people receiving care management at two time points during which two
government policy initiatives were implemented to promote greater standardization
in health and social care provision for older people in England. Findings at Time
2 revealed that there were higher levels of physical and mental impairment and
more health care assessments undertaken. There was a slight decrease in home care
receipt but a marginal increase of more intensive home care provision. Service
users living with a carer were less likely to receive home care but more likely
to receive respite care or day care than those living alone. The policy goal of
widening access to specialist health and social care services for older people
with mental health problems was achieved. Guidance that focused eligibility
criteria on the identification of older people with complex needs required the
availability of appropriate support and services. Irrespective of policy
initiatives, the sociodemographic characteristics of older people and the
availability of informal support are principal determinants of service provision.
PMID- 25118513
TI - Increased longevity in HIV: caring for older HIV-infected adults.
AB - The demographics of the HIV-infected population in the United States have shifted
in a way that few would have predicted 30 years ago when the tide of sick and
dying patients largely consisted of young men. Effective ART has allowed those
infected to live long, productive lives and to grow old with their disease. With
the increase in life expectancy afforded by HIV treatment, the cause of death
among HIV-infected individuals is far more likely to be from an HIV-associated
non-AIDS condition. Nonetheless, HIV seems to accelerate the aging process, and
care providers involved in the treatment of older patients with HIV need to be
aware that their patients are at increased risk of developing various common
disorders, compared to uninfected same-age patients. Clinicians need to remain
vigilant to the possibility of a new diagnosis of HIV among their older patients.
Awareness of current or distant risk, frank discussions of sexual practices, and
willingness to offer routine testing are crucial to making this diagnosis, with
the recognition that longevity for patients with HIV is directly linked to how
soon they enter care. HIV infection adds another challenge to the management of
older patients; geriatricians and HIV specialists need to coordinate their
efforts to provide patients with comprehensive multidisciplinary care. Older
patients with HIV also have social and psychological needs that extend beyond the
medical office. Maintaining independence, acknowledging limitations, reducing
risk of adverse events such as falls or medication errors, and supporting self
acceptance and awareness are only a few of the many areas where care providers
outside the medical office can be important for patients' ongoing well-being.
Accessing family support, community outreach, church affiliation, or other
outpatient support networks can be useful for patients. The remarkable change in
prognosis brought about by effective ART in the mid-1990s has meant that HIV is
now, for many, a manageable chronic illness. Clinicians and other care providers
are changing their approach and goals of care as patients with HIV grow old.
PMID- 25118514
TI - Constipation in the long-term care setting.
PMID- 25118516
TI - Yet another new era?
PMID- 25118517
TI - Medical consultations for dental patients in 2014.
PMID- 25118518
TI - Focus on: impressions.
PMID- 25118519
TI - Light coaxes stem cells to repair teeth.
PMID- 25118520
TI - Majority of dental professionals believe implant guidelines necessary for optimal
patient outcomes.
PMID- 25118521
TI - High-need dental clinic coming to St. Louis.
PMID- 25118522
TI - Dental schools name new deans.
PMID- 25118524
TI - States' and communities' fluoridation efforts honored.
PMID- 25118523
TI - "Pass that bottle to me!". Red wine's cavity-fighting benefits are once again
verified.
PMID- 25118525
TI - Orthodontic forced eruption: a team approach in aesthetic treatment.
PMID- 25118526
TI - Endodontic canal preparation: innovations in glide path management and shaping
canals.
PMID- 25118527
TI - Preformed design bridging concept: a case report.
PMID- 25118528
TI - A multipurpose temporary tooth replacement: aesthetic tooth-borne alternative
used prior to an implant.
PMID- 25118529
TI - Simplifying cementation of high-strength restorations: using an improved resin
modified glass ionomer cement.
PMID- 25118530
TI - Placement of a modified subperiosteal implant: a clinical solution to help those
with no bone.
PMID- 25118531
TI - Two-stage mini dental implants: is it time to join the party?
PMID- 25118532
TI - A multidisciplinary team approach improves outcomes: treatment of an
aesthetically conscious patient with gingival recession.
PMID- 25118533
TI - Neurosurgery in South Africa.
PMID- 25118535
TI - Physician, heal thyself: creative writing as a tool for self-care and enhancing
care of others.
PMID- 25118534
TI - Hereditary haemorrhagic telangiectasia in North African and sub-Saharan patients.
PMID- 25118536
TI - The neglected triple disease burden and interaction of helminths, HIV and
tuberculosis: an opportunity for integrated action in South Africa.
PMID- 25118537
TI - Palliative care: definition of euthanasia.
PMID- 25118538
TI - Prof. McQuoid-Mason responds.
PMID- 25118539
TI - Palliative care: preventing misconceptions.
PMID- 25118540
TI - Prof. McQuoid-Mason responds.
PMID- 25118541
TI - WHIDMT: Rossouw and Howard blatantly miss the point.
PMID- 25118543
TI - E Cape health officials nearly turn TB victims into cash cows.
PMID- 25118542
TI - Community service doctors 'slaves to the state'--court challenge.
PMID- 25118544
TI - Quack remedy cast--'we were pawns, not told, didn't know, won't say, don't care'.
PMID- 25118545
TI - Ivan James Nurick.
PMID- 25118546
TI - Hessel Utian.
PMID- 25118547
TI - Diagnosis and management of Pompe disease.
AB - Pompe disease (PD) is an autosomal-recessively inherited neuromuscular disease
that, if not diagnosed and treated early, can be fatal. It can present from early
infancy into adulthood. Due to the lack of acid alpha-glucosidase, there is
progressive intracellular accumulation of glycogen. The severity of the disease
is determined by age of onset, organ involvement including the degree of severity
of muscle involvement, as well as rate of progression. PD is classified into two
groups: infantile and late-onset, each having two subgroups. The need for two
tests performed by separate methods (screening and confirmatory) is outlined. It
is imperative to try to reduce the time to diagnosis and to recognise the
possibilities of false-positive results. A multidisciplinary team approach to
treatment of affected patients is optimum with, as team leader, a physician who
has experience in managing this rare disorder. In this article, we present a
brief overview of the disease and provide guidelines for diagnosis and management
of this condition in South Africa.
PMID- 25118548
TI - The Teddy Bear Clinic Constitutional Court case: sexual conduct between
adolescent consenting children aged under 16 years decriminalised and a
moratorium on the reporting duties of doctors and others.
AB - The Constitutional Court in the Teddy Bear Clinic appeal case held that the
sections of the Sexual Offences Act that impose criminal liability for sexual
offences on adolescent children under 16 years of age are invalid. The invalidity
was suspended for 18 months to allow Parliament to correct the Act's defects. A
moratorium was imposed on all investigations into, arrests in, prosecutions in,
and criminal and ancillary proceedings regarding such section 15 and 16 offences.
This includes the duty to report consensual sexual conduct between children under
16 years of age in terms of section 54 of the Act--pending Parliament's
correction. However, it is submitted that the 'best interests of the child'
principle in the Children's Act and the Constitution should guide all obligatory
reporting situations involving sexual and other conduct of children, irrespective
of whether they are adolescents under 16 years old or between 16 and 17 years
old.
PMID- 25118549
TI - The risks of gastrointestinal injury due to ingested magnetic beads.
AB - Accidental ingestion of foreign bodies is a common problem in children. Magnetic
bead toys are hazardous, having potentially lethal consequences if ingested.
These magnets conglomerate in different segments of bowel, causing pressure
necrosis, perforation and/or fistula formation anywhere along the
gastrointestinal tract. A clinical diagnostic pitfall is that the appearance on
the initial abdominal radiograph may be misinterpreted by the uninitiated as a
single metallic object without any intervening intestinal wall. Symptoms do not
occur until complications have developed, and even then, unless magnet ingestion
is suspected, treatment may initially be mistakenly expectant, as with any other
foreign body. After observing a case of multiple magnet ingestion that led to the
rapid onset of small-bowel inter-loop fistulas and peritonitis, we attempted to
reproduce the likely sequence of events in a laboratory setting using fresh, post
mortem porcine bowel as an animal model and placing magnetic toy beads within the
bowel lumen. Pressure-induced perforation appeared extremely rapidly, replicating
the operative findings in two of our cases. We propose that if magnet ingestion
is suspected, early endoscopic or surgical retrieval is mandatory. Appropriate,
rapid surgical intervention is indicated. Laparoscopy offers a minimally invasive
therapeutic option.
PMID- 25118550
TI - The safety of osteoporosis medication.
AB - Osteoporosis is a common, costly and serious disease, which is still too often
regarded as an inevitable part of the normal ageing process and therefore sub
optimally treated, especially in the elderly--in fact, only two out of every 10
patients who sustain a hip fracture receive any form of assessment or
prophylactic therapy for osteoporosis. One out of five patients die within 1 year
after a hip fracture, and < 50% are capable of leading an independent life. Yet
very effective anti-fracture therapy, capable of reducing fracture risk by 35 -
60%, is available. A number of publications have recently questioned the safety
of drugs routinely used to treat patients with osteoporosis. This paper attempts
to put the situation into perspective and expresses the National Osteoporosis
Foundation of South Africa's view on the safety of these drugs. Their efficacy in
preventing skeletal fractures and their cost-effectiveness are not addressed in
any detail. The paper emphasises the fact that all osteoporosis medications have
side-effects, some of which are potentially life-threatening.
PMID- 25118551
TI - Acute intermittent porphyria presenting as progressive muscular atrophy in a
young black man.
AB - Acute intermittent porphyria, the most common porphyria affecting the nervous
system, typically presents with neurovisceral crises followed by a motor
neuropathy. We describe a 23-year-old black South African man presenting with a
progressive stuttering, lower motor neuron syndrome developing over months. He
had not experienced pain or neuropsychiatric symptoms. One year after symptom
onset he was bed-bound with a flaccid quadriparesis. There was marked amyotrophy,
but without fasciculations. Sensation was intact apart from a hypo-aesthetic
patch over the thigh. Electrophysiological investigations showed an active motor
axonopathy. Urinary porphyrins, delta-aminolaevulinic acid and porphobilinogen
were elevated. Mutation analysis revealed the c445C>T (R149X) mutation in the
porphobilinogen deaminase gene. The patient responded dramatically to haem
arginate and could walk with assistance 2 weeks later. We identified the first
molecularly confirmed acute intermittent porphyria in a black South African. The
clinical presentation mimicked a progressive lower motor neuron syndrome.
PMID- 25118552
TI - The neurological manifestations of the acute porphyrias.
PMID- 25118553
TI - Increased visibility and discoverability of South African health-related
research.
PMID- 25118554
TI - High prevalence of cisplatin-induced ototoxicity in Cape Town, South Africa.
AB - BACKGROUND: Cisplatin is administered as the first-line treatment of soft-tissue
cancers. It has a reported cure rate of up to 85%, but is associated with a high
incidence of ototoxicity, characterised by irreversible bilateral hearing loss
and affecting 23 - 50% of adults who receive the drug. OBJECTIVES: To determine
the incidence of cisplatin-induced ototoxicity at Groote Schuur Hospital (GSH),
Cape Town, South Africa. METHODS: retrospective cross-sectional study of
cisplatin-receiving cancer patients attending GSH between January 2006 and August
2011. RESULTS: A total of 377 patients were recorded as receiving cisplatin
therapy during the study period. A 300% increase in new cisplatin-receiving
patients receiving audiological monitoring was observed between 2006 and 2010.
However, only patients with all clinical data as well as baseline and follow-up
audiometric analyses were investigated. One hundred and seven such patients were
identified, 55.1% of whom developed cisplatin-induced ototoxicity while receiving
high-dose (> or = 60 mg/m2) cisplatin treatment. Higher cumulative cisplatin
dosages were associated with development of significant hearing loss (p = 0.027).
The odds of developing cisplatin-induced hearing loss were elevated for patients
with head and neck tumours and lymphoma (p = 0.0465 and p = 0.0563, respectively)
and were significantly lower for those with reproductive cancers (p = 0.0371).
CONCLUSION: Comprehensive audiological monitoring should be available for every
patient during cisplatin treatment to minimise the development of disabling
hearing loss.
PMID- 25118555
TI - Angiotensin converting enzyme inhibitors v. angiotensin receptor blockers in the
management of hypertension: a funder's perspective.
AB - BACKGROUND: Hypertension poses a huge financial risk to any funder/medical aid,
including the risk-mitigating strategies provided by the managed care
organisations that are required to manage patients with hypertension. The South
African Hypertension Guideline states that the choice of therapy--an angiotensin
converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB)-
should be based on cost and tolerability. OBJECTIVE: To assess the costs of ACEIs
v. ARBs in the management of hypertensive patients and the prevention of
cardiovascular complications for a private medical aid scheme in South Africa.
METHOD: A Phase IV observational, retrospective cohort study of over 480 000
beneficiaries between 2010 and 2011 was undertaken. Hypertensive patients were
identified by their chronic medication authorisation and were categorised into
three groups: ACEI, ARB and combined groups. A cost-benefit analysis was
performed on the claims data, comparing the input costs in rand against the
downstream costs using analysis of variance. RESULTS: Data from 28 165 patients
were included in the study. Based on the health economic analysis that was
performed, there was no statistically significant difference in the input costs
between the ACEI and the ARB groups. However, a statistically significant
reduction in the downstream costs was observed in the ACEI group v. the ARB and
combined groups (p < 0.0001). CONCLUSION: It is more cost beneficial to treat
chronic hypertensive patients with an ACEI than ARBs in preventing cardiovascular
related complications. It is recommended that managed care companies continue
recommending ACEIs rather than ARBs in the treatment of hypertensive patients.
PMID- 25118556
TI - Mammographic screening for breast cancer in a resource-restricted environment.
AB - BACKGROUND: Mammographic screening is carried out at public sector hospitals as
part of clinical practice. OBJECTIVE: We report the experience of such screening
at Tygerberg Academic Hospital (TBAH), a tertiary referral hospital in the
Western Cape Province, South Africa. METHODS: All mammograms performed between
2003 and 2012 at TBAH were analysed regarding patient demographics, clinical
data, indication and outcome according to the American College of Radiology
Breast Imaging Reporting and Data System (BIRADS). Screening mammography was
offered to patients > 40 years of age and mammograms were read by experienced
breast surgeons. Patients with BIRADS 3 and 4 lesions were recalled for short
term follow-up, further imaging or tissue acquisition. Patients with BIRADS 5
lesions were recalled for tissue acquisition. Further imaging, method of tissue
acquisition, histology results and use of neo-adjuvant therapy were also
recorded. RESULTS: Of 16 105 mammograms, 3 774 (23.4%) were carried out for
screening purposes. The median age of patients undergoing screening was 54 years.
Of 407 women with mammograms that were reported as BIRADS 3 - 5 (10.8% of
screening mammograms), 187 (46% of recalled women) went on to have further
imaging only. Tissue was acquired in 175 patients (43% of recalled women),
comprising a biopsy rate of 4.6% of the total series. The malignancy rate in
cases in which tissue acquisition was done was 25%. Forty-three breast cancers
were diagnosed (11.4/1 000 examinations). Of the cancers, nine (31%) were ductal
carcinomas in situ. Of 20 invasive cancers, nine (45%) were < 10 mm in size. Of
the invasive cancers, 40% were node-positive. CONCLUSIONS: The cancer diagnosis
rate indicates a high breast cancer load in an urbanised population.
PMID- 25118557
TI - Results of a pilot programme of mammographic breast cancer screening in the
Western Cape.
AB - BACKGROUND: Mammographic screening programmes are now established in developing
countries. We present an analysis of the first screening programme in sub-Saharan
Africa. METHODS: Women aged > or = 40 years were identified at three primary
healthcare centres in the Western Cape Province, South Africa, and after giving
informed consent underwent mammography at a mobile unit. After a single reading,
patients with American College of Radiology Breast Imaging Reporting and Data
System (BIRADS) 3 - 5 lesions were referred to a tertiary centre for further
management. RESULTS: Between 1 February 2011 and 31 August 2012, 2 712 screening
mammograms were performed. A total of 261 screening mammograms were reported as
BIRADS 3 - 5 (recall rate 9.6%). Upon review of the 250 available screening
mammograms, 58 (23%) were rated benign or no abnormalities (BIRADS 1 and 2) and
no further action was taken. In 32 women, tissue was acquired (biopsy rate for
the series 1.2%); 10 cancers were diagnosed (biopsy malignancy rate 31%). For the
entire series of 2 712 screening mammograms, the cancer diagnosis rate was 3.7/1
000 examinations. Of 10 cancers diagnosed at screening, 5 were TNM clinical stage
0, 2 stage I and 3 stage II. CONCLUSIONS: The low cancer detection rate achieved,
and the technical and multiple administrative problems experienced do not justify
installation of a screening programme using the model utilised in this series.
PMID- 25118558
TI - Community v. non-community assault among adults in Khayelitsha, Western Cape,
South Africa: a case count and comparison of injury severity.
AB - BACKGROUND: Community assault (CA) or vigilantism is widespread in the township
of Khayelitsha, Cape Town, South Africa (SA). Anecdotal evidence suggests that
victims of CA are worse off than other assault cases. However, scientific data on
the rate and severity of CA cases are lacking for SA. OBJECTIVES: To contribute
to CA prevention and management strategies by estimating the rate of CA among
adults in Khayelitsha and comparing the injury severity and survival probability
between cases of CA and other assault (non-CA) cases. METHODS: We studied four
healthcare centres in Khayelitsha during July - December 2012. A consecutive case
series was conducted to capture all CA cases during this period. A retrospective
folder review was performed on all cases of CA and on a control group of non-CA
cases to compare injury severity and estimate survival probability. RESULTS: A
total of 148 adult cases of CA occurred (case rate 1.1/1 000 person-years) over
the study period. The Injury Severity Scores (ISSs) in the CA group were
significantly higher than in the non-CA group (p < 0.001), with a median
(interquartile range) ISS of 3 (2 - 6) in CA cases v. 1 (1 - 2) in non-CA cases.
Comparison between the CA v. non-CA groups showed that a Glasgow Coma Scale < 15
(20.1% v. 5.4%, respectively), referral to the tertiary hospital (33.8% v. 22.6%,
respectively), and crush syndrome (25.7% v. 0.0%, respectively) were all more
common in CA cases. Survival probabilities were similar in both groups (CA v. non
CA 99.2% v. 99.3%, respectively). CONCLUSION: The rate of CA among adults in
Khayelitsha is high, and the severity of injuries sustained by CA victims is
substantially higher than in other assault cases.
PMID- 25118559
TI - Self-induction of abortion among women accessing second-trimester abortion
services in the public sector, Western Cape Province, South Africa: an
exploratory study.
AB - BACKGROUND: Despite South Africa's liberal abortion law permitting abortion on
request in the first trimester and under restricted conditions for second
trimester pregnancies, the practice of unsafe self-induced abortion persists.
However, the prevalence of this practice, the methods used and the reasons behind
it are relatively under-researched. As part of a larger study seeking to improve
abortion services in the Western Cape Province, we explored reports of prior
attempts to self-induce abortion among women undergoing legal second-trimester
abortion. OBJECTIVES: To describe the prevalence and methods of and factors
related to unsuccessful attempts at self-induction of abortion by women
presenting without complications and seeking second-trimester abortion at public
health facilities in the Western Cape. METHODS: In a cross-sectional study from
April to August 2010, 194 consenting women undergoing second-trimester abortion
were interviewed by trained fieldworkers using structured questionnaires at four
public sector facilities near Cape Town. RESULTS: Thirty-four women (17.5%; 95%
confidence interval 12.7 - 23.4) reported an unsuccessful attempt to self-induce
abortion during the current pregnancy before going to a facility for second
trimester abortion. No factors were significantly associated with self-induction,
but a relatively high proportion of this small sample were unemployed and spoke
an indigenous African language at home. A readily available herbal product called
Stametta was most commonly used; other methods included taking tablets bought
from unlicensed providers and using other herbal remedies. No use of physical
methods was reported. CONCLUSIONS: The prevalence of unsafe self-induction of
abortion is relatively high in the Western Cape. Efforts to inform women in the
community about the availability of free services in the public sector and to
educate them about the dangers of self-induction and unsafe providers should be
strengthened to help address this public health issue.
PMID- 25118560
TI - Clinicians ignore best practice guidelines: prospective audit of cardiac injury
marker ordering in patients with chest pain.
AB - BACKGROUND: Chest pain is a frequent presenting symptom and is a diagnostic
challenge. Recent recommendations state that high-sensitivity cardiac troponin
assays are the only biochemical test required in the diagnosis of acute coronary
syndrome (ACS) and that other biomarkers such as myoglobin or creatine kinase
(CK)-MB isoform are not indicated. OBJECTIVE: To establish whether clinician
ordering in the setting of suspected ACS was in keeping with recent
recommendations. METHODS: A prospective audit was undertaken of all requests for
cardiac troponin I (cTnI) and CK-MB received at a large tertiary hospital in
Durban, South Africa, during a 20-day period in December 2012. RESULTS: A total
of 193 cardiac marker requests were received: 12 (6.2%) requests were for cTnI
alone; 8 (4.1%) were for CK-MB alone; and the remaining 173 (89.7%) were for both
cTnI and CK-MB. Therefore, a total of 181 (93.8%) incorrect requests were
received during this period. A total of 103 (53.4%) patients had values below the
cut-off point of 40 ng/l for cTnI, i.e. ACS was ruled out. Of these, 15 had CK-MB
values above the reference interval. A total of 12 (6.2%) patients had cTnI
values > 500 ng/l, i.e. ACS was ruled in; 33.3% of this group had normal CK-MB
values. CONCLUSION: Ordering patterns in the setting of ACS did not reflect
current recommendations and were wasteful and potentially dangerous.
PMID- 25118561
TI - Hepatitis B and HIV co-infection in pregnant women: indication for routine
antenatal hepatitis B virus screening in a high HIV prevalence setting.
AB - BACKGROUND: Sub-Saharan Africa is endemic for hepatitis B virus (HBV) and human
immunodeficiency virus (HIV) infections. HBV/HIV co-infection in women of
reproductive age is of clinical and public health importance because these women
constitute a significant reservoir for horizontal and perinatal HBV transmission.
Childhood HBV vaccination from 6 weeks of age protects most children against
chronic HBV infection. However, infants born to HBV/HIV co-infected women are
more likely to be infected perinatally, with an increased risk of chronic
hepatitis, than infants born to HBV mono-infected women. OBJECTIVES: The aim of
our study was to establish the prevalence of HBV infection and HBV/HIV co
infection in pregnant women in KwaZulu-Natal, South Africa, to inform antenatal
HBV screening and childhood immunisation policies in South Africa. METHODS:
Stored plasma specimens obtained from 570 pregnant women were tested for
hepatitis B surface antigen (HBsAg) and HBV infectivity, as characterised by the
presence of hepatitis B e antigen (HBeAg) and/or HBV DNA load. RESULTS: The
antenatal HIV prevalence and HBsAg prevalence in this study were 41.6% and 5.3%
(95% confidence interval (CI) 3.4 - 7.1), respectively. Overall, 3.1% (95% CI 1.7
- 4.6) of pregnant women were HBV/HIV co-infected, with HBeAg positivity and the
HBV DNA load being significantly higher in co-infected women. CONCLUSION: We
report a 5.3% HBV prevalence and a 3.1% HBV/HIV co-infection prevalence in
pregnant women from this HIV-endemic region. Routine antenatal HBV screening will
allow early identification of neonates who require HBV active-passive
immunoprophylaxis at birth. This strategy, together with antenatal
antiretrovirals, will reduce the risk of perinatal HBV transmission, especially
in high-risk HBV/ HIV co-infected pregnant women.
PMID- 25118562
TI - Transition from child- to adult-orientated care for children with long-term
health conditions: a process, not an event.
AB - Long-term health conditions in childhood include both congenital conditions and
acquired diseases. Children with long-term health conditions face issues and
potential secondary problems that are different from those of adults with chronic
diseases. Transition to adult-orientated care for such children and adolescents
is a major challenge. Transition needs to be prepared for and planned. A variety
of possible transition models exists, depending on circumstances.
PMID- 25118563
TI - Aedes aegypti larvicide from the ethanolic extract of Piper nigrum black
peppercorns.
AB - Due to unavailability of a vaccine and a specific cure to dengue, the focus
nowadays is to develop an effective vector control method against the female
Aedes aegypti mosquito. This study aims to determine the larvicidal fractions
from Piper nigrum ethanolic extracts (PnPcmE) and to elucidate the identity of
the bioactive compounds that comprise these larvicidal fractions. Larvicidal
assay was performed by subjecting 3rd to 4th A. aegypti instar larvae to PnPcmE
of P. nigrum. The PnPcmE exhibited potential larvicidal activity having an LC50
of 7.1246 +/- 0.1304 ppm (mean +/- Std error). Normal phase vacuum liquid
chromatography of the PnPcmE was employed which resulted in five fractions, two
of which showed larvicidal activity. The most active of the PnPcmE fractions is
PnPcmE-1A, with an LC50 and LC90 of 1.7101 +/- 0.0491 ppm and 3.7078 ppm,
respectively. Subsequent purification of PnPcmE-1A allowed the identification of
the larvicidal compound as oleic acid.
PMID- 25118564
TI - The relationships between adult attachment, theoretical orientation, and
therapist-reported alliance quality among licensed psychologists.
AB - OBJECTIVE: Attachment anxiety has been depicted as an undesirable therapist
characteristic based on findings that preoccupied therapists, relative to those
with other attachment styles, report more ruptures in the therapeutic alliance.
What has not been considered, however, is the extent to which attachment dynamics
are related to theoretical orientations and how attachment styles and theoretical
orientations combine to predict therapists' perceptions of the quality of their
alliances. METHOD: The present surveyed 290 licensed psychologists nationally.
RESULTS: Results revealed that even within a sample of primarily secure
psychologists, higher 15 levels of attachment anxiety correlated positively with
the endorsement of psychodynamic orientations, and negatively with the
endorsement of cognitive-behavioral orientations and self-reported alliance
quality. Endorsement of cognitive-behavioral orientations, in turn, correlated
positively with therapist-reported alliance quality. CONCLUSION: The results are
discussed in terms of the extent to which attachment dimensions should be
considered in therapists' understandings of their therapeutic alliances.
PMID- 25118565
TI - Efficient planar perovskite solar cells based on 1.8 eV band gap CH3NH3PbI2Br
nanosheets via thermal decomposition.
AB - Hybrid organometallic halide perovskite CH3NH3PbI2Br (or MAPbI2Br) nanosheets
with a 1.8 eV band gap were prepared via a thermal decomposition process from a
precursor containing PbI2, MABr, and MACl. The planar solar cell based on the
compact layer of MAPbI2Br nanosheets exhibited 10% efficiency and a single
wavelength conversion efficiency of up to 86%. The crystal phase, optical
absorption, film morphology, and thermogravimetric analysis studies indicate that
the thermal decomposition process strongly depends on the composition of
precursors. We find that MACl functions as a glue or soft template to control the
initial formation of a solid solution with the main MAPbI2Br precursor components
(i.e., PbI2 and MABr). The subsequent thermal decomposition process controls the
morphology/surface coverage of perovskite films on the planar substrate and
strongly affects the device characteristics.
PMID- 25118566
TI - Erectile dysfunction in psoriasis patients.
AB - BACKGROUND: An association between psoriasis and sexual dysfunction has been
explored. However, not much is known about the factors behind erectile
dysfunction in these patients. OBJECTIVES: To compare the prevalence and the
severity of erectile dysfunction in patients with and without psoriasis and to
determine potential associations between erectile dysfunction and psoriasis
patients' characteristics. MATERIALS & METHODS: An observational cross-sectional
study was conducted at two tertiary hospital-based Dermatology departments.
Consecutive adult men with psoriasis or other skin conditions were recruited.
Data were collected using an anonymous, self-completed, designed questionnaire,
which included the Dermatology Life Quality Index and the 5-item version of the
International Index of Erectile Function. RESULTS: A total of 135 psoriasis
patients and 201 controls were included. Psoriasis patients had a higher
prevalence of erectile dysfunction than controls (61.5% vs 43.8%, p = 0.001), and
an increased risk of more severe forms of erectile dysfunction. Dermatology Life
Quality Index, genital psoriasis and psoriasis duration were not associated with
the presence of erectile dysfunction. In multivariate logistic regression,
psoriasis and diabetes were found to be independent risk factors for erectile
dysfunction with estimated odds ratios of 2.28 (CI 95%, 1.40-3.27) and 3.49 (CI
95%, 1.40-8.66), respectively. CONCLUSION: This study suggests psoriasis as a
risk factor for erectile dysfunction. Atherosclerosis is a plausible connecting
link, adding up to the already acknowledged effect of psychological factors in
these patients. From a clinical standpoint, because erectile dysfunction may
precede overt cardiovascular disease, it can be used as a precocious marker of
cardiovascular risk in psoriatic men.
PMID- 25118567
TI - Selective interception of gelsolin amyloidogenic stretch results in
conformationally distinct aggregates with reduced toxicity.
AB - The pathogenesis of protein misfolding diseases is attributed to the cytotoxicity
caused by amyloidogenic prefibrillar aggregates, rather than mature fibrils. The
presence of one or more amyloidogenic stretches in different proteins has been
proven critical for initiating fibril formation. In the present study, we show
that two natural compounds, curcumin and emetine, bind tightly (Kd < 1.6 MUM) to
the core amyloidogenic stretch (182-192) of gelsolin (AGel). Binding happens in
different structural orientations, distinctly modulating the amyloidogenic
pathway of AGel. While AGel alone undergoes sigmoidal transition to thioflavin T
(ThT)-responsive fibrillar aggregates with clear lag phase, the presence of
curcumin or emetine abolishes the lag phase and produces starkly different,
noncytotoxic end products. Atomic force microscopy revealed that while curcumin
augments fibril formation, emetine arrests it at an intermediate aggregated stage
with no fibrillar morphology. FTIR spectroscopy, dynamic light scattering, and
ANS fluorescence experiments also suggest that these two species are distinct.
Curcumin and emetine also differentially affect the preformed amyloids with the
former thickening the fibrils and the latter releasing reclusive oligomers. MD
simulations further provided mechanistic insights of differential interaction by
the two compounds modulating amyloid formation. The results were also confirmed
on the disease-associated amyloidogenic fragment of gelsolin (fAGel). Thus, our
findings suggest that targeting amyloidogenic stretches in proteins could be
useful in designing novel molecules against protein misfolding diseases.
PMID- 25118569
TI - Microbial community response to chlorine conversion in a chloraminated drinking
water distribution system.
AB - Temporary conversion to chlorine (i.e., "chlorine burn") is a common approach to
controlling nitrification in chloraminated drinking water distribution systems,
yet its effectiveness and mode(s) of action are not fully understood. This study
characterized occurrence of nitrifying populations before, during and after a
chlorine burn at 46 sites in a chloraminated distribution system with varying
pipe materials and levels of observed nitrification. Quantitative polymerase
chain reaction analysis of gene markers present in nitrifying populations
indicated higher frequency of detection of ammonia oxidizing bacteria (AOB) (72%
of samples) relative to ammonia oxidizing archaea (AOA) (28% of samples).
Nitrospira nitrite oxidizing bacteria (NOB) were detected at 45% of samples,
while presence of Nitrobacter NOB could not be confirmed at any of the samples.
During the chlorine burn, the numbers of AOA, AOB, and Nitrospira greatly reduced
(i.e., 0.8-2.4 log). However, rapid and continued regrowth of AOB and Nitrospira
were observed along with nitrite production in the bulk water within four months
after the chlorine burn, and nitrification outbreaks appeared to worsen 6-12
months later, even after adopting a twice annual burn program. Although high
throughput sequencing of 16S rRNA genes revealed a distinct community shift and
higher diversity index during the chlorine burn, it steadily returned towards a
condition more similar to pre-burn than burn stage. Significant factors
associated with nitrifier and microbial community composition included water age
and sampling location type, but not pipe material. Overall, these results
indicate that there is limited long-term effect of chlorine burns on nitrifying
populations and the broader microbial community.
PMID- 25118568
TI - Early cortical thickness change after mild traumatic brain injury following motor
vehicle collision.
AB - In a motor vehicle collision (MVC), survivors often receive mild traumatic brain
injuries (mTBI). Although there have been some reports of early white matter
changes after an mTBI, much less is known about early cortical structural
changes. To investigate early cortical changes within a few days after an MVC, we
compared cortical thickness of mTBI survivors with non-mTBI survivors, then
reexamined cortical thickness in the same survivors 3 months later. MVC survivors
were categorized as mTBI or non-mTBI based on concussive symptoms documented in
emergency departments (EDs). Cortical thickness was measured from MRI images
using FreeSurfer within a few days and again at 3 months after MVC. Post
traumatic stress symptoms and physical conditions were also assessed. Compared
with the non-mTBI group (n = 23), the mTBI group (n = 21) had thicker cortex in
the left rostral middle frontal (rMFG) and right precuneus gyri, but thinner
cortex in the left posterior middle temporal gyrus at 7.2 +/- 3.1 days after MVC.
After 3 months, cortical thickness had decreased in left rMFG in the mTBI group
but not in the non-mTBI group. The cortical thickness of the right precuneus
region in the initial scans was positively correlated with acute traumatic stress
symptoms for all survivors and with the number of reduced activity days for mTBI
survivors who completed the follow-up. The preliminary results suggest that
alterations in cortical thickness may occur at an early stage of mTBI and that
frontal cortex structure may change dynamically over the initial 3 months after
mTBI.
PMID- 25118571
TI - Rare earth elements supply restrictions: market failures, not scarcity, hamper
their current use in high-tech applications.
PMID- 25118573
TI - Cochlear Meniere's Disease in Association With a High Jugular Bulb.
PMID- 25118574
TI - A Case of Rotational Vertebral Artery Syndrome.
PMID- 25118572
TI - Development and evaluation of a truncated recombinant NS3 antigen-based indirect
ELISA for detection of pestivirus antibodies in sheep and goats.
AB - The aim of this study was to develop an indirect ELISA using the helicase domain
of bovine viral diarrhoea virus (BVDV) NS3 protein instead of full-length NS3
protein for detection of BVDV and BDV antibodies in sheep and goats and its
validation by comparing its sensitivity and specificity with virus neutralization
test (VNT) as the reference test. The purified 50 kDa recombinant NS3 protein was
used as the coating antigen in the ELISA. The optimal concentration of antigen
was 320 ng/well at a serum dilution of 1:20 and the optimal positive cut-off
optical density value was 0.40 based on test results of 418 VNT negative sheep
and goat sera samples. When 569 serum samples from sheep (463) and goats (106)
were tested, the ELISA showed a sensitivity of 91.71% and specificity of 94.59%
with BVDV VNT. A good correlation (93.67%) was observed between the two tests. It
showed a sensitivity of 85% and specificity of 86.6% with VNT in detecting BDV
antibody positive or negative samples. This study demonstrates the efficacy of
truncated recombinant NS3 antigen based ELISA for seroepidemiological study of
pestivirus infection in sheep and goats.
PMID- 25118570
TI - HOIL-1L functions as the PKCzeta ubiquitin ligase to promote lung tumor growth.
AB - RATIONALE: Protein kinase C zeta (PKCzeta) has been reported to act as a tumor
suppressor. Deletion of PKCzeta in experimental cancer models has been shown to
increase tumor growth. However, the mechanisms of PKCzeta down-regulation in
cancerous cells have not been previously described. OBJECTIVES: To determine the
molecular mechanisms that lead to decreased PKCzeta expression and thus increased
survival in cancer cells and tumor growth. METHODS: The levels of expression of
heme-oxidized IRP2 ubiquitin ligase 1L (HOIL-1L), HOIL-1-interacting protein
(HOIP), Shank-associated RH domain-interacting protein (SHARPIN), and PKCzeta
were analyzed by Western blot and/or quantitative real-time polymerase chain
reaction in different cell lines. Coimmunoprecipitation experiments were used to
demonstrate the interaction between HOIL-1L and PKCzeta. Ubiquitination was
measured in an in vitro ubiquitination assay and by Western blot with specific
antibodies. The role of hypoxia-inducible factor (HIF) was determined by
gain/loss-of-function experiments. The effect of HOIL-1L expression on cell death
was investigated using RNA interference approaches in vitro and on tumor growth
in mice models. Increased HOIL-1L and decreased PKCzeta expression was assessed
in lung adenocarcinoma and glioblastoma multiforme and documented in several
other cancer types by oncogenomic analysis. MEASUREMENTS AND MAIN RESULTS:
Hypoxia is a hallmark of rapidly growing solid tumors. We found that during
hypoxia, PKCzeta is ubiquitinated and degraded via the ubiquitin ligase HOIL-1L,
a component of the linear ubiquitin chain assembly complex (LUBAC). In vitro
ubiquitination assays indicate that HOIL-1L ubiquitinates PKCzeta at Lys-48,
targeting it for proteasomal degradation. In a xenograft tumor model and lung
cancer model, we found that silencing of HOIL-1L increased the abundance of
PKCzeta and decreased the size of tumors, suggesting that lower levels of HOIL-1L
promote survival. Indeed, mRNA transcript levels of HOIL-1L were elevated in
tumor of patients with lung adenocarcinoma, and in a lung adenocarcinoma tissue
microarray the levels of HOIL-1L were associated with high-grade tumors.
Moreover, we found that HOIL-1L expression was regulated by HIFs. Interestingly,
the actions of HOIL-1L were independent of LUBAC. CONCLUSIONS: These data provide
first evidence of a mechanism of cancer cell adaptation to hypoxia where HIFs
regulate HOIL-1L, which targets PKCzeta for degradation to promote tumor
survival. We provided a proof of concept that silencing of HOIL-1L impairs lung
tumor growth and that HOIL-1L expression predicts survival rate in cancer
patients suggesting that HOIL-1L is an attractive target for cancer therapy.
PMID- 25118575
TI - Feasibility of a synthetic temporal bone for training in mastoidectomy: face,
content, and concurrent validity.
AB - OBJECTIVE: To investigate the face, content, and concurrent validity of the
synthetic Pettigrew temporal bone (PTB) for mastoidectomy training as compared
with cadaveric temporal bone (CTB). STUDY DESIGN: A prospective evaluation study.
METHODS: Participants were invited to perform a step-by-step modified radical
mastoidectomy using both bones and complete a 22-item, 5-point Likert scale
questionnaire. The questionnaire is divided into 4 domains: face validity (FV),
global content (GC), task-specific content (TSC), and curriculum recommendation
(CR). RESULTS: Thirty-six experts and 89 trainees completed all tasks, 63 using
CTB and 62 using PTB. The PTB median FV was 4 (IQR: 4-5), GC of 4 (IQR: 4-5), TSC
of 4 (IQR: 3-4), and CR of 4 (IQR: 4-5). The CTB was rated significantly higher
than PTB by both groups in all domains; CTB FV: 5 (IQR: 4-5), GC: 5 (IQR: 4-5),
TSC: 5 (IQR: 4-5), and CR: 5 (IQR: 5-5), p < 0.001 for each. Trainees rated PTB
significantly higher than experts in all domains. There was no statistically
significant difference between experts and trainees in rating the CTB in all
domains. PTB gives similar haptic feedback to CTB, allows the use of suction and
irrigation, has the important landmarks painted for identification, and contains
articulating ossicles. The facial nerve anatomy was found to be inaccurate around
the region of the second genu. CONCLUSION: Participants found PTB to be valid for
teaching some, yet not all, aspects of mastoid surgery, and experts agreed that
it could improve global transferrable otologic skills. It is essential that the
facial nerve anatomy is addressed before recommending this model.
PMID- 25118576
TI - Hearing preservation cochlear implantation in adolescents.
AB - OBJECTIVE: This study describes our experience of cochlear implantation (CI) with
hearing preservation in adolescents. Our aim was to determine if hearing
preservation is successful in this population, if the preserved hearing is
maintained, and what the potential benefit of preserving hearing in this
population is. PATIENTS: Fourteen profoundly deaf adolescents with preservation
of low-frequency hearing (125, 250, and 500 Hz). INTERVENTION: Twelve adolescents
had a single-sided CI, and two had bilateral CI. All were having their first
implantation, and all patients had hearing preservation surgery (soft surgery).
MAIN OUTCOME MEASURES: Hearing preservation was measured with preoperative and
postoperative pure-tone audiograms. Speech audiometry was performed before
implantation and at subsequent follow-up appointments. RESULTS: Hearing
preservation (measurable hearing thresholds) was achieved in 13 of 14 patients.
Average follow-up was 2 years 10 months (range, 4 mo-4 yr 9 mo). Three of 13
patients with initial successful hearing preservation had deterioration of their
hearing at subsequent follow-up. The addition of naturally preserved hearing to
the cochlear implant improved speech audiometry scores compared with using the
implants in isolation. CONCLUSION: This study demonstrates that residual hearing
can be consistently preserved and maintained in adolescents during the short
/medium-term using a soft surgical technique to insert standard-length
electrodes. The potential benefit of preserving residual low-frequency hearing
seems to be improvement in speech discrimination in challenging hearing
conditions, although larger studies are required.
PMID- 25118578
TI - Minimal Growth of Intracochlear Schwannoma Over 7 Years.
PMID- 25118577
TI - The correlation between obesity, obstructive sleep apnea, and superior
semicircular canal dehiscence: a new explanation for an increasingly common
problem.
AB - OBJECTIVE: To investigate rates of obesity and obstructive sleep apnea (OSA) in
patients with a diagnosis of superior semicircular canal dehiscence (SSCD). STUDY
DESIGN: Retrospective cohort study. SETTING: Two tertiary referral centers.
PATIENTS: Thirty-one patients with SSCD were identified from patient records at
Yale between January 1, 2003 and August 1, 2013 and from the University of
Cincinnati between November 1, 2008 and November 1, 2013. The control cohort
consisted of 100 consecutive adult patients who obtained high-resolution CT
imaging of their temporal bones at Yale University for any reason. INTERVENTIONS:
CT images were reviewed by two authors in double blind fashion and patient data
was analyzed statistically. MAIN OUTCOME MEASURES: Rates of OSA, body mass index
(BMI), and presence of tegmental defects in patients with SSCD were compared to
the control cohort. RESULTS: The 31 patients with SSCD demonstrated higher BMIs
[SSCD avg. 31.62, standard deviation (SD) 8.6 vs. no SSCD 28.01, SD 6.3, P =
0.036], rates of OSA (SSCD 29.03% vs. no SSCD 7.00, P = 0.001), and rates of
tegmental defects (SSCD avg. 64.5% vs. no SSCD 16%, P = 1.24 * 10(-7)), in
comparison to the control cohort. SSCD was found in 6 of 100 consecutively
reviewed adult CT scans and in 0 of 41 scans obtained in those under 17 years of
age. CONCLUSIONS: Patients with SSCD demonstrated higher BMIs, higher rates of
OSA, and were more likely to have accompanying tegmental defects. These results
may support a possible causality between increased intracranial pressure and the
formation of superior semicircular canal dehiscence.
PMID- 25118579
TI - A United Kingdom survey of concerns, needs, and priorities reported by patients
diagnosed with acoustic neuroma.
AB - INTRODUCTION: The Patient Concerns Inventory-Acoustic Neuroma (PCI-AN) was
developed to explore specifically the concerns that patients would like to
discuss during their clinic consultation. The PCI covers a range of issues
including hearing, intimacy, fatigue, financial/benefits, relationships, regret,
and support for family. It also lists multidisciplinary team (MDT) members that
patients would like to see or be referred on to. METHOD: The PCI-AN was emailed
to members of the British Acoustic Neuroma Association. RESULTS: A total of 465
complete (54.5%) responses were received. There were 284 female and 181 male
subjects. Overall, the most common treatment modality was surgical excision
(47%). A quarter of the study cohort had stereotactic radiosurgery, whereas 23%
were conservatively managed with interval MRI scanning. The remaining 5% had both
surgery and stereotactic radiosurgery. From the 55-item PCI-AN, the most commonly
selected issues that patients wanted to talk about were related to the physical
and functional well-being and treatment received. Tinnitus was the most
frequently selected issue (46%), followed by fatigue/tiredness (43%), dizziness
(33%), further investigation (39%), acoustic neuroma treatment (38%), and energy
levels (32%). More than a quarter of the respondents had fears of their acoustic
neuroma recurring (29%), had concerns about their facial appearance/ palsy (29%),
or suffered pain in the head and neck region (26%). The 3 health-care
professionals patients most wanted to talk with either in clinic or by referral
were as follows: ENT/neurosurgeon (39%), vestibular (balance) physiotherapist
(39%), and audiologist (39%). Although it was unknown how many respondents had
facial palsy, 21% wanted to see a facial palsy physiotherapist, and another 10%
sought referral to a plastic surgeon. CONCLUSION: The PCI-AN has shed light on an
interesting array of issues, which may be overlooked by clinicians in busy skull
base clinic. The PCI-AN allows for patient-directed consultation and ultimately
empowers them to be actively involved in the management of their health.
PMID- 25118580
TI - Graft take-rates after tympanoplasty: results from a prospective ear surgery
database.
AB - OBJECTIVE: To present a prospective ear surgery database and investigate the
graft take-rate and prognostic factors for graft take-rate in tympanoplasty using
the database. STUDY DESIGN: Prospective database study. SETTING: Tertiary
referral center. PATIENTS: A total of 1606 cases undergoing tympanoplasty types I
to IV were registered in the database in the period from February 2004 to
November 2013. INTERVENTION: A total of 837 cases underwent
myringoplasty/tympanoplasty type I. MAIN OUTCOME MEASURE: Graft take-rate and
prognostic factors (age, discharge at time of surgery, tuba function, technique,
graft material, and revision surgery) for tympanoplasty type I were studied. A
comparison with the graft take-rates for tympanoplasty types II to IV and/or
cholesteatoma was made. RESULTS: A user-friendly ear surgery database with fast
data entry and direct import of audiometric data was developed. The graft take
rate was found to be 93.0% at 2 to 6 months and 86.6% at more than 12 months.
Except for a discharging ear at the time of surgery, no significant differences
using chi2 test of association were found when comparing graft take-rates for
different prognostic factors or more advanced tympanoplasty with or without
cholesteatoma. A long-term graft take-rate overestimation of 6% was found if
cases with defaulted follow-up because of early reperforation were not included.
CONCLUSION: A prospective database can be used to study prognostic factors and
reduce bias in reporting the graft take-rate. Prospective databases are needed
for high-quality longitudinal studies but require a continuous and daily effort
of involved surgeons and therefore need to be convenient and fast to use.
PMID- 25118581
TI - Assessing Treatment Efficacy and Progression of Necrotizing Otitis Externa.
PMID- 25118582
TI - Cochlear Implantation in the Setting of Cochlear Ossification as Sequela of
Malarial Meningitis.
PMID- 25118583
TI - Neurofibromatosis 2 invasion of the internal auditory canal wall: clinical
significance.
AB - OBJECTIVE: To describe the infiltration of severe phenotype ("Wishart")
neurofibromatosis type 2 (NF2)-related vestibular nerve schwannomas (VSs) into
the internal auditory canal wall in contrast to sporadic VS and the milder
("Gardner") phenotype NF2-related VS. STUDY DESIGN: Retrospective case series
involving microscopic examination and review of clinical history. SETTING:
Temporal bone laboratory, harboring 849 documented pairs of decalcified, formalin
fixed, celloidin-embedded, sectioned human temporal bones (hTBs) with clinical
history. SUBJECTS AND METHODS: Histologic sections from 56 patients who had been
treated by the House Clinic for VS and who had pledged their temporal bones were
identified in the data base of the laboratory. Twenty-four hTBs were from
individuals with NF2.Each series of sections was examined microscopically for
evidence of invasion of the walls of the internal auditory canal (IAC), hearing
thresholds, speech discrimination, score (SDS), and tumor recurrence. RESULTS:
Infiltration of the walls of the IAC by small buds of VS was found in 17 of the
24 NF2 hTBs. The only 2 NF2 without invasion were from an elderly patient with
the milder (Gardner) form of NF2. Ten of the 12 NF2 patients had undergone
surgery for the removal of their tumor, but residual tumor remained in the bone
surrounding the IAC. Invasive VS were associated with poorer hearing thresholds
at 250, 500, 1,000, and 2,000 Hz and lower SDS score. A relationship between
invasion and recurrence was not statistically significant. CONCLUSION: The
majority of IAC tumors associated with the severe "Wishart" phenotype demonstrate
bone invasion within the IAC. Invasion of bone was associated with poorer
hearing. The invasive nature of NF2-associated tumors may partially explain their
higher recurrence rate after resection. Surgeons managing NF2-related VS should
be aware of the small infiltrations of the wall of the IAC when removing these
tumors to minimize recurrence.
PMID- 25118584
TI - Round window electrocochleography and speech perception outcomes in adult
cochlear implant subjects: comparison with audiometric and biographical
information.
AB - HYPOTHESIS: Intraoperative round window (RW) electrocochleography (ECoG) can help
predict speech perception outcomes in adult cochlear implant (CI) recipients.
BACKGROUND: Speech perception outcomes using CIs are highly variable. Recent data
demonstrated that intraoperative ECoG could account for nearly half the variance
in postoperative word scores. The present study seeks to update this correlation
with a larger sample size and determine if addition of clinical variables
improves the prediction. METHODS: Intraoperative RW ECoG was performed in adult
subjects undergoing CI. Amplitudes of the ongoing response to tone bursts of
multiple frequencies at 85 to 95 dB HL were summed to obtain the total response
(ECoG-TR). ECoG-TR was correlated with postoperative speech perception scores.
Multiple linear regression was used to combine clinical factors with the ECoG-TR.
RESULTS: The ECoG-TR accounted for 40% of the variance in CNC word scores (n =
32). The preoperative pure tone average (PTA) was the only clinical factor with a
significant correlation (r2 = 20%). The ability to predict word scores using ECoG
TR and PTA, or after addition of age and duration of hearing loss, was not
significantly different from using ECoG-TR alone. For 2 outliers, ECoG-TR
predicted a better word score than obtained. CONCLUSIONS: The measurement of
cochlear physiology before CI, reduced to a single variable, is a better
predictor of postoperative speech perception than common clinical factors.
Additional analysis of the outliers showed that waveform morphology can provide
distinct information in individual cases.
PMID- 25118586
TI - Why no Unilateral Vestibular Atelectasis?
PMID- 25118585
TI - Inactivation of specific Pseudomonas aeruginosa biofilm factors does not alter
virulence in infected cholesteatomas.
AB - HYPOTHESIS: When experimental cholesteatomas are infected with Pseudomonas
aeruginosa (PA) mutants lacking factors associated with the formation of
biofilms, host defenses are more effective against these strains when compared
with wild-type strains (PAO1 and OPPA8) in preventing tissue destruction.
BACKGROUND: Previous studies have identified biofilms within chronically infected
aural cholesteatomas. These infected cholesteatomas are associated with increased
tissue destruction. Because biofilms are highly resistant to host defenses
leading to prolonged infection, we propose that the biofilm phenotype of P.
aeruginosa may be a virulence factor leading to persistence of infection and
increased tissue destruction. METHODS: Aural cholesteatomas were induced in
Mongolian gerbils. At the time of induction, the ear canals were inoculated with
wild-type (PAO1 and OPPA8) and biofilm-deficient (PAO1 DeltapilA, PAO1
algD::aacC1 and PAO1 galU::aacC1) strains of P. aeruginosa. After 8 weeks, the
size of the cholesteatomas and levels of bone destruction and deposition were
measured using microCT scanning and double fluorochrome bone labeling. RESULT:
Infected cholesteatomas resulted in increased growth, bone destruction, and bone
deposition when compared with vehicle-only controls. We observed no differences
between the wild-type (biofilm forming) and the biofilm-deficient strains of P.
aeruginosa. CONCLUSION: Our hypothesis that biofilm formation is a virulence
factor in cholesteatomas infected with P. aeruginosa was not supported. A number
of interpretations of these data are reasonable. It is possible that biofilms are
not critical in infected cholesteatomas. Alternatively, the mutants that are
deficient in generating biofilms in vitro may be able to form effective biofilms
in vivo using alternative pathways.
PMID- 25118587
TI - "Off-on" electrochemiluminescence system for sensitive detection of ATP via
target-induced structure switching.
AB - An "off-on" electrochemiluminescence (ECL) strategy was constructed for highly
sensitive and selective detection of adenosine 5'-triphosphate (ATP) with a
quantum dots (QDs) modified electrode and a DNAzyme signal probe. The immobilized
QDs were functionalized with a DNA sequence (DNA1) and then aptamer for
recognition of target analyte. The signal probe was prepared by assembling
another DNA sequence (DNA2) and G-quadruplex on gold nanoparticle via Au-S
chemistry, which was used to bind the probe to electrode surface through a
hybridization reaction with aptamer and hemin for forming G-quadruplex/hemin
DNAzyme, respectively. Upon the sandwich hybridization of DNA1-aptamer-DNA2, the
signal probe could be captured on the aptasensor to catalyze the reduction of
dissolved oxygen, the coreactant for cathodic ECL emission of QDs, leading to a
decrease of ECL intensity and thus the "off" state. In the presence of target,
its recognition by aptamer led to the release of aptamer from electrode surface
and decreased the amount of captured signal probe, thus the ECL emission was in
its "on" state. The "off-on" strategy resulted from the target-induced structure
switching could be used for specific detection of ATP with a linear range of 8
2000 nM and a detection limit of 7.6 nM. The proposed aptasensor could be
successfully applied in the ECL detection of ATP in human serum. This method
could resist environmental interfering agents and be extended for sensitive and
reliable detection of a wide range of analytes in complex sample.
PMID- 25118588
TI - Fate and transport of selected estrogen compounds in Hawaii soils: effect of soil
type and macropores.
AB - The fate and transport of estrogen compounds in the environment is of increasing
concern due to their potential impact on freshwater organisms, ecosystems and
human health. The behavior of these compounds in batch experiments suggests low
mobility, while field studies indicate the persistence of estrogen compounds in
the soil with the possibility of migration to surface water as well as
groundwater. To better understand the movement of these chemicals through soils,
we examined their transport in three different Hawaiian soils and two aqueous
matrices. The three different soils used were an Oxisol, a Mollisol and a cinder,
characterized by different mineralogical properties and collected at depths of 60
90 cm and 210-240 cm. Two liquid matrices were used; deionized (DI) water
containing calcium chloride (CaCl2), and recycled water collected from a
wastewater treatment facility. The experiments were conducted in packed and
structured columns. Non-equilibrium conditions were observed during the study,
especially in the structured soil. This is believed to be primarily related to
the presence of macropores in the soil. The presence of macropores resulted in
reduced contact time between soil and estrogens, which facilitated their
transport. We found that the organic carbon content and mineralogical composition
of the soils had a profound effect on the transport of the estrogens. The
mobility of estrone (E1) and 17beta-estradiol (E2) was greater in cinder than in
the other soils. In column experiments with recycled water, earlier breakthrough
peaks and longer tails of estrogens were produced compared to those observed
using DI water. The use of recycled water for agricultural purposes and the
siting of septic tanks and cesspools should be critically reviewed in light of
these findings, especially in areas where groundwater is the primary source of
potable water, such as Hawaii.
PMID- 25118590
TI - Preliminary study of an offline simultaneous determination of metoprolol tartrate
and hydrochlorothiazide in powders and tablets by reflectance near-infrared
spectroscopy.
AB - A preliminary study of the feasibility of using near-infrared spectroscopy (NIRS)
for the offline simultaneous determination of metoprolol tartrate (MTP) and
hydrochlorothiazide (HTZ) in powders and tablets has been carried out. An
industrial tableting process was simulated using an instrumented tablet press
replicator - PressterTM. Conventional reference analytics were replaced with
gravimetric analysis. The NIRS models for powder and tablet analysis were
developed using 55 samples, and tested on 80 independent samples. Powder mixture
components were weighed in glass vials to collect reference values, mixed and
manually transferred to a tablet press replicator and compacted to form tablets.
NIRS calibration models were developed using spectral and gravimetric reference
data. The two model drugs were simultaneously quantified exhibiting root mean
squared error of prediction (RMSEP) of 1.69 and 1.31 mg for HTZ powder and tablet
samples, respectively, and RMSEP of 3.15 and 3.00 mg for MTP powder and tablet
samples, respectively. NIRS analysis of MTP and HTZ in powder and tablet form has
not been reported elsewhere.
PMID- 25118591
TI - Effect of simulated precompression, compression pressure and tableting speed on
an offline diffuse transmittance and reflectance near-infrared spectral
information of model intact caffeine tablets.
AB - Near-infrared spectroscopy (NIRS) is used in the pharmaceutical industry for
monitoring drug content during the tablet manufacturing process. It is of
critical importance to understand the effect of process factors on NIRS
performance. Design of Experiments (DoE) methodology was applied in this work for
the systematic study of the effects of compression pressure, precompression
pressure and tableting speed on an average Euclidean distance (AED), which
reflects spectral features of the tablets, and root mean-squared error of
prediction (RMSEP) as key performance indicator of NIRS calibration models.
Caffeine tablets were manufactured in 17 experimental runs in accordance with D
optimal design. Developed diffuse transmittance (DT) and diffuse reflectance (DR)
calibration models were tested on five independent test sets to confirm the
conclusions of the DoE. Compression pressure and tableting speed have shown
significant effect on the studied responses in DT mode, whereas all three studied
factors have shown a significant effect in DR mode. Significant factors were
considered in the development of the global calibration models. The authors
suggest further study of RMSEP and AED responses to draw reliable conclusions on
the effects of tableting process factors. The global calibration model in DT mode
has shown superior performance compared to DR mode.
PMID- 25118589
TI - RasGRP3 limits Toll-like receptor-triggered inflammatory response in macrophages
by activating Rap1 small GTPase.
AB - Host immune cells can detect and destruct invading pathogens via pattern
recognition receptors. Small Rap GTPases act as conserved molecular switches
coupling extracellular signals to various cellular responses, but their roles as
regulators in Toll-like receptor (TLR) signalling have not been fully elucidated.
Here we report that Ras guanine nucleotide-releasing protein 3 (RasGRP3), a
guanine nucleotide-exchange factor activating Ras and Rap1, limits production of
proinflammatory cytokines (especially IL-6) in macrophages by activating Rap1 on
activation by low levels of TLR agonists. We demonstrate that RasGRP3, a dominant
member of RasGRPs in macrophages, impairs TLR3/4/9-induced IL-6 production and
relieves dextrane sulphate sodium-induced colitis and collagen-induced arthritis.
In RasGRP3-deficient RAW264.7 cells obtained by CRISPR-Cas9 genome editing,
TLR3/4/9-induced activation of Rap1 was inhibited while ERK1/2 activation was
enhanced. Our study suggests that RasGRP3 limits inflammatory response by
activating Rap1 on low-intensity pathogen infection, setting a threshold for
preventing excessive inflammatory response.
PMID- 25118593
TI - Effect of seasonal variation on adult clinical laboratory parameters in Rwanda,
Zambia, and Uganda: implications for HIV biomedical prevention trials.
AB - OBJECTIVES: To investigate the effect of seasonal variation on adult clinical
laboratory parameters in Rwanda, Zambia, and Uganda and determine its
implications for HIV prevention and other clinical trials. METHODS: Volunteers in
a cross-sectional study to establish laboratory reference intervals were asked to
return for a seasonal visit after the local season had changed from dry to rainy
or vice versa. Volunteers had to be clinically healthy, not pregnant and negative
for HIV, Hepatitis B and C, and syphilis infection at both visits. At each visit,
blood was taken for measurement of hemoglobin, haematocrit, mean corpuscular
volume, red blood cells, platelets, total white blood cells (WBC), neutrophils,
lymphocytes, monocytes, eosinophils, basophils, CD4/CD8 T cells, aspartate
aminotransferase, alanine aminotransferase, alkaline phosphatase, direct
bilirubin, total bilirubin, total immunoglobulin gamma, total protein,
creatinine, total amylase, creatine phosphokinase and lactate dehydrogenase
(LDH). Consensus dry season reference intervals were applied to rainy season
values (and vice versa) and the proportion of 'out-of-range' values determined.
Percentage differences between dry and rainy season parameter mean values were
estimated. RESULTS: In this cohort of 903 volunteers, less than 10.0% of
consensus parameter (except LDH) values in one season were "out-of-range" in the
other. Twenty-two (22) percent of rainy season LDH values fell outside of the
consensus dry season interval with the higher values observed in the rainy
season. Variability between consensus seasonal means ranged from 0.0% (total WBC,
neutrophils, monocytes, basophils, and direct bilirubin) to 40.0% (eosinophils).
Within sites, the largest seasonal variations were observed for monocytes
(Masaka, 11.5%), LDH (Lusaka, 21.7%), and basophils (Kigali, 22.2%). CONCLUSIONS:
Seasonality had minimal impact on adult clinical laboratory parameter values in
Rwanda, Zambia, and Uganda. Seasonal variation may not be an important factor in
the evaluation of adult clinical laboratory parameters in HIV prevention and
other clinical trials in these countries.
PMID- 25118592
TI - Discovery of a rare pterosaur bone bed in a cretaceous desert with insights on
ontogeny and behavior of flying reptiles.
AB - A pterosaur bone bed with at least 47 individuals (wing spans: 0.65-2.35 m) of a
new species is reported from southern Brazil from an interdunal lake deposit of a
Cretaceous desert, shedding new light on several biological aspects of those
flying reptiles. The material represents a new pterosaur, Caiuajara dobruskii
gen. et sp. nov., that is the southermost occurrence of the edentulous clade
Tapejaridae (Tapejarinae, Pterodactyloidea) recovered so far. Caiuajara dobruskii
differs from all other members of this clade in several cranial features,
including the presence of a ventral sagittal bony expansion projected inside the
nasoantorbital fenestra, which is formed by the premaxillae; and features of the
lower jaw, like a marked rounded depression in the occlusal concavity of the
dentary. Ontogenetic variation of Caiuajara dobruskii is mainly reflected in the
size and inclination of the premaxillary crest, changing from small and inclined
(~ 115 degrees ) in juveniles to large and steep (~ 90 degrees ) in adults. No
particular ontogenetic features are observed in postcranial elements. The
available information suggests that this species was gregarious, living in
colonies, and most likely precocial, being able to fly at a very young age, which
might have been a general trend for at least derived pterosaurs.
PMID- 25118594
TI - Increased lymph node yield in colorectal cancer is not necessarily associated
with a greater number of lymph node positive cancers.
AB - The presence of lymph node metastasis is a key prognostic factor in colorectal
cancer and lymph node yield is an important parameter in assessing the quality of
histopathology reporting of colorectal cancer excision specimens. This study
assesses the trend in lymph node evaluation over time in a single institution and
the relationship with the identification of lymph node positive tumours. It
compares the lymph node yield of a contemporary dataset compiled from the
histopathology reports of 2178 patients who underwent surgery for primary
colorectal cancer between 2005 and 2012 with that of a historic dataset compiled
from the histopathology reports of 1038 patients who underwent surgery for
colorectal cancer at 5 yearly intervals from 1975 to 2000. The mean lymph node
yield was 14.91 in 2005 rising to 21.38 in 2012. In 2012 92.9% of all cases had
at least 12 lymph nodes examined. Comparison of the mean lymph node yield and
proportion of Dukes C cases shows a significant increase (Pearson correlation =
0.927, p = 0.001) in lymph node yield while there is no corresponding significant
trend in the proportion of Dukes C cases (Pearson correlation = -0.138, p =
0.745). This study shows that there is increasing yield of lymph nodes from
colorectal cancer excision specimens. However, this is not necessarily associated
with an increase number of lymph node positive cancers. Further risk stratifying
of colorectal cancer requires consideration of other pathological parameters
especially the presence of extramural venous invasion and relevant biomarkers.
PMID- 25118595
TI - Saccharomyces boulardii modifies Salmonella typhimurium traffic and host immune
responses along the intestinal tract.
AB - Salmonella enterica serovar Typhimurium (ST) is an enteropathogenic Gram-negative
bacterium that causes infection following oral ingestion. ST spreads rapidly
along the gastrointestinal tract (GIT) and invades the intestinal epithelium to
ultimately reach internal body organs. The probiotic yeast Saccharomyces
boulardii BIOCODEX (S.b-B) is prescribed for prophylaxis of diarrheal infectious
diseases. We previously showed that S.b-B prevents weight loss in ST-infected
mice and significantly decreases bacterial translocation to the spleen and liver.
This study was designed to investigate the effect of S.b-B on ST migration along
the GIT and the impact of the yeast on the host's early innate immune responses.
Bioluminescent imaging (BLI) was used to evaluate the effect of S.b-B on the
progression of luminescent Salmonella Typhimurium (ST-lux) in the GIT of mice
pretreated with streptomycin. Photonic emission (PE) was measured in GIT extracts
(stomach, small intestine, cecum and colon) at various time periods post
infection (PI). PE analysis revealed that, 45 min PI, ST-lux had migrated
slightly faster in the mice treated with S.b-B than in the untreated infected
animals. At 90 min PI, ST-lux had reached the cecum in both groups of mice.
Adhesion of ST to S.b-B was visualized in the intestines of the mice and probably
accounts for (1) the faster elimination of ST-lux in the feces, and (2) reduced
translocation of ST to the spleen and liver. In the early phase of infection, S.b
B also modifies the host's immune responses by (1) increasing IFN-gamma gene
expression and decreasing IL-10 gene expression in the small intestine, and (2)
elevating both IFN-gamma, and IL-10 mRNA levels in the cecum. BLI revealed that
S.b-B modifies ST migration and the host immune response along the GIT. Study
findings shed new light on the protective mechanisms of S.b-B during the early
phase of Salmonella pathogenesis.
PMID- 25118596
TI - Copy number variation in Thai population.
AB - Copy number variation (CNV) is a major genetic polymorphism contributing to
genetic diversity and human evolution. Clinical application of CNVs for
diagnostic purposes largely depends on sufficient population CNV data for
accurate interpretation. CNVs from general population in currently available
databases help classify CNVs of uncertain clinical significance, and benign CNVs.
Earlier studies of CNV distribution in several populations worldwide showed that
a significant fraction of CNVs are population specific. In this study, we
characterized and analyzed CNVs in 3,017 unrelated Thai individuals genotyped
with the Illumina Human610, Illumina HumanOmniexpress, or Illumina HapMap550v3
platform. We employed hidden Markov model and circular binary segmentation
methods to identify CNVs, extracted 23,458 CNVs consistently identified by both
algorithms, and cataloged these high confident CNVs into our publicly available
Thai CNV database. Analysis of CNVs in the Thai population identified a median of
eight autosomal CNVs per individual. Most CNVs (96.73%) did not overlap with any
known chromosomal imbalance syndromes documented in the DECIPHER database. When
compared with CNVs in the 11 HapMap3 populations, CNVs found in the Thai
population shared several characteristics with CNVs characterized in HapMap3.
Common CNVs in Thais had similar frequencies to those in the HapMap3 populations,
and all high frequency CNVs (>20%) found in Thai individuals could also be
identified in HapMap3. The majorities of CNVs discovered in the Thai population,
however, were of low frequency, or uniquely identified in Thais. When performing
hierarchical clustering using CNV frequencies, the CNV data were clustered into
Africans, Europeans, and Asians, in line with the clustering performed with
single nucleotide polymorphism (SNP) data. As CNV data are specific to origin of
population, our population-specific reference database will serve as a valuable
addition to the existing resources for the investigation of clinical significance
of CNVs in Thais and related ethnicities.
PMID- 25118597
TI - Sclerostin blood levels before and after kidney transplantation.
AB - BACKGROUND/AIMS: Sclerostin is secreted by osteocytes. As a circulating inhibitor
of the Wnt-signaling pathway it inhibits bone formation and contributes to the
development of osteoporosis. Sclerostin levels are elevated in patients with
chronic kidney disease and end-stage renal disease. Since data for patients after
kidney transplantation are scarce, we have prospectively measured sclerostin
levels before and during the first year after renal transplantation and have
examined the association of sclerostin with parameters of bone mineral metabolism
and with bone mineral density. METHODS: Sclerostin levels were measured by ELISA
in 42 consecutive renal transplant recipients before and at defined intervals in
the first year after transplantation. Bone mineral density was measured by dual
energy X-ray absorptiometry. RESULTS: Pre-transplant serum sclerostin levels were
elevated in all patients (61.8 +/- 32.3 pmol/l, normal range 20-30 pmol/l).
Within 15 days after transplantation and correlating with the improvement of
renal function, sclerostin levels dropped to 21.0 +/- 14.7 pmol/l and
subsequently increased to 23.8 +/- 14.9 and 28.0 +/- 16.8 pmol/l after 6 and 12
months, respectively (P<0.001). A linear mixed model indicated that pre
transplant sclerostin levels (P<0.001) and time after transplantation (P<0.001)
were the most important predictors for the rise of post-transplant sclerostin
levels. No correlation was found between post-transplant sclerostin levels and
bone mineral density. CONCLUSIONS: The rapid reduction of elevated serum
sclerostin levels shortly after kidney transplantation parallels the improvement
of renal function, but contrasts with the more delayed improvement of
hyperparathyroidism. The normalization of both hormones could contribute to
improved bone health after renal transplantation.
PMID- 25118598
TI - Cyclic variations in incubation conditions induce adaptive responses to later
heat exposure in chickens: a review.
AB - Selection programs have enabled broiler chickens to gain muscle mass without
similar enlargement of the cardiovascular and respiratory systems that are
essential for thermoregulatory efficiency. Meat-type chickens cope with high
ambient temperature by reducing feed intake and growth during chronic and
moderate heat exposure. In case of acute heat exposure, a dramatic increase in
morbidity and mortality can occur. In order to alleviate heat stress in the long
term, research has recently focused on early thermal manipulation. Aimed at
stimulation of long-term thermotolerance, the thermal manipulation of embryos is
a method based on fine tuning of incubation conditions, taking into account the
level and duration of increases in temperature and relative humidity during a
critical period of embryogenesis. The consequences of thermal manipulation on the
performance and meat quality of broiler chickens have been explored to ensure the
potential application of this strategy. The physiological basis of the method is
the induction of epigenetic and metabolic mechanisms that control body
temperature in the long term. Early thermal manipulation can enhance poultry
resistance to environmental changes without much effect on growth performance.
This review presents the main strategies of early heat exposure and the
physiological concepts on which these methods were based. The cellular mechanisms
potentially underlying the adaptive response are discussed as well as the
potential interest of thermal manipulation of embryos for poultry production.
PMID- 25118599
TI - 1alpha,25-dihydroxyvitamin D3 ameliorates seawater aspiration-induced acute lung
injury via NF-kappaB and RhoA/Rho kinase pathways.
AB - INTRODUCTION: Inflammation and pulmonary edema are involved in the pathogenesis
of seawater aspiration-induced acute lung injury (ALI). Although several studies
have reported that 1alpha,25-Dihydroxyvitamin D3 (calcitriol) suppresses
inflammation, it has not been confirmed to be effective in seawater aspiration
induced ALI. Thus, we investigated the effect of calcitriol on seawater
aspiration-induced ALI and explored the probable mechanism. METHODS: Male SD rats
receiving different doses of calcitriol or not, underwent seawater instillation.
Then lung samples were collected at 4 h for analysis. In addition, A549 cells and
rat pulmonary microvascular endothelial cells (RPMVECs) were cultured with
calcitriol or not and then stimulated with 25% seawater for 40 min. After these
treatments, cells samples were collected for analysis. RESULTS: Results from real
time PCR showed that seawater stimulation up-regulated the expression of vitamin
D receptor in lung tissues, A549 cells and RPMVECs. Seawater stimulation also
activates NF-kappaB and RhoA/Rho kinase pathways. However, we found that
pretreatment with calcitriol significantly inhibited the activation of NF-kappaB
and RhoA/Rho kinase pathways. Meanwhile, treatment of calcitriol also improved
lung histopathologic changes, reduced inflammation, lung edema and vascular
leakage. CONCLUSIONS: These results demonstrated that NF-kappaB and RhoA/Rho
kinase pathways are critical in the development of lung inflammation and
pulmonary edema and that treatment with calcitriol could ameliorate seawater
aspiration-induced ALI, which was probably through the inhibition of NF-kappaB
and RhoA/Rho kinase pathways.
PMID- 25118603
TI - Hepatocellular carcinoma: gender differences.
PMID- 25118604
TI - Microenvironment: HSF1, the troublemaker next door.
PMID- 25118605
TI - Evidence for prehistoric origins of Egyptian mummification in late Neolithic
burials.
AB - Traditional theories on ancient Egyptian mummification postulate that in the
prehistoric period (i.e. the Neolithic and Chalcolithic periods, 5th and 4th
millennia B.C.) bodies were naturally desiccated through the action of the hot,
dry desert sand. Although molding of the body with resin-impregnated linen is
believed to be an early Pharaonic forerunner to more complex processes,
scientific evidence for the early use of resins in artificial mummification has
until now been limited to isolated occurrences during the late Old Kingdom (c.
2200 B.C.), their use becoming more apparent during the Middle Kingdom (c. 2000
1600 BC). We examined linen wrappings from bodies in securely provenanced tombs
(pit graves) in the earliest recorded ancient Egyptian cemeteries at Mostagedda
in the Badari region (Upper Egypt). Our investigations of these prehistoric
funerary wrappings using a combination of gas chromatography-mass spectrometry
(GC-MS) and thermal desorption/pyrolysis (TD/Py)-GC-MS have identified a pine
resin, an aromatic plant extract, a plant gum/sugar, a natural petroleum source,
and a plant oil/animal fat in directly AMS-dated funerary wrappings. Predating
the earliest scientific evidence by more than a millennium, these embalming
agents constitute complex, processed recipes of the same natural products, in
similar proportions, as those utilized at the zenith of Pharaonic mummification
some 3,000 years later. The antibacterial properties of some of these ingredients
and the localized soft-tissue preservation that they would have afforded lead us
to conclude that these represent the very beginnings of experimentation that
would evolve into the famous mummification practice of the Pharaonic period.
PMID- 25118607
TI - Experimental study of the vortex-induced vibration of drilling risers under the
shear flow with the same shear parameter at the different Reynolds numbers.
AB - A considerable number of studies for VIV under the uniform flow have been
performed. However, research on VIV under shear flow is scarce. An experiment for
VIV under the shear flow with the same shear parameter at the two different
Reynolds numbers was conducted in a deep-water offshore basin. Various
measurements were obtained by the fiber bragg grating strain sensors.
Experimental data were analyzed by modal analysis method. Results show several
valuable features. First, the corresponding maximum order mode of the natural
frequency for shedding frequency is the maximum dominant vibration mode and multi
modal phenomenon is appeared in VIV under the shear flow, and multi-modal
phenomenon is more apparent at the same shear parameter with an increasing
Reynolds number under the shear flow effect. Secondly, the riser vibrates at the
natural frequency and the dominant vibration frequency increases for the effect
of the real-time tension amplitude under the shear flow and the IL vibration
frequency is the similar with the CF vibration frequency at the Reynolds number
of 1105 in our experimental condition and the IL dominant frequency is twice the
CF dominant frequency with an increasing Reynolds number. In addition, the
displacement trajectories at the different locations of the riser appear the same
shape and the shape is changed at the same shear parameter with an increasing
Reynolds number under the shear flow. The diagonal displacement trajectories are
observed at the low Reynolds number and the crescent-shaped displacement
trajectories appear with an increasing Reynolds number under shear flow in the
experiment.
PMID- 25118602
TI - Mechanisms of disseminated cancer cell dormancy: an awakening field.
AB - Metastases arise from residual disseminated tumour cells (DTCs). This can happen
years after primary tumour treatment because residual tumour cells can enter
dormancy and evade therapies. As the biology of minimal residual disease seems to
diverge from that of proliferative lesions, understanding the underpinnings of
this new cancer biology is key to prevent metastasis. Analysis of approximately 7
years of literature reveals a growing focus on tumour and normal stem cell
quiescence, extracellular and stromal microenvironments, autophagy and
epigenetics as mechanisms that dictate tumour cell dormancy. In this Review, we
attempt to integrate this information and highlight both the weaknesses and the
strengths in the field to provide a framework to understand and target this
crucial step in cancer progression.
PMID- 25118606
TI - Acute effects of particulate matter and black carbon from seasonal fires on peak
expiratory flow of schoolchildren in the Brazilian Amazon.
AB - BACKGROUND: Panel studies have shown adverse effects of air pollution from
biomass burning on children's health. This study estimated the effect of current
levels of outdoor air pollution in the Amazonian dry season on peak expiratory
flow (PEF). METHODS: A panel study with 234 schoolchildren from 6 to 15 years old
living in the municipality of Tangara da Serra, Brazil was conducted. PEF was
measured daily in the dry season in 2008. Mixed-effects models and unified
modelling repeated for every child were applied. Time trends, temperature,
humidity, and subject characteristics were regarded. Inhalable particulate matter
(PM10), fine particulate matter (PM2.5), and black carbon (BC) effects were
evaluated based on 24-hour exposure lagged by 1 to 5 days and the averages of 2
or 3 days. Polynomial distributed lag models (PDLM) were also applied. RESULTS:
The analyses revealed reductions in PEF for PM10 and PM2.5 increases of 10
ug/m(3) and 1 ug/m(3) for BC. For PM10, the reductions varied from 0.15
(confidence interval (CI)95%: -0.29; -0.01) to 0.25 l/min (CI95%: -0.40; -0.10).
For PM2.5, they ranged from 0.46 (CI95%: -0.86 to -0.06) to 0.54 l/min (CI95%:
0.95; -0.14). As for BC, the reduction was approximately 1.40 l/min. In relation
to PDLM, adverse effects were noticed in models based on the exposure on the
current day through the previous 3 days (PDLM 0-3) and on the current day through
the previous 5 days (PDLM 0-5), specially for PM10. For all children, for PDLM 0
5 the global effect was important for PM10, with PEF reduction of 0.31 l/min
(CI95%: -0.56; -0.05). Also, reductions in lags 3 and 4 were observed. These
associations were stronger for children between 6 and 8 years old. CONCLUSION:
Reductions in PEF were associated with air pollution, mainly for lagged exposures
of 3 to 5 days and for younger children.
PMID- 25118608
TI - Roles of birds and bats in early tropical-forest restoration.
AB - Restoration of tropical forest depended in large part on seed dispersal by fruit
eating animals that transported seeds into planted forest patches. We tested
effectiveness of dispersal agents as revealed by established recruits of tree and
shrub species that bore seeds dispersed by birds, bats, or both. We documented
restoration of dispersal processes over the first 76 months of experimental
restoration in southern Mexico. Mixed-model repeated-measures randomized-block
ANOVAs of seedlings recruited into experimental controls and mixed-species
plantings from late-secondary and mature forest indicated that bats and birds
played different roles in the first years of a restoration process. Bats
dispersed pioneer tree and shrub species to slowly regenerating grassy areas,
while birds mediated recruitment of later-successional species into planted
stands of trees and to a lesser extent into controls. Of species of pioneer trees
and shrubs established in plots, seven were primarily dispersed by birds, three
by bats and four by both birds and bats. Of later-successional species recruited
past the seedling stage, 13 were of species primarily dispersed by birds, and six
were of species dispersed by both birds and bats. No later-successional species
primarily dispersed by bats established in control or planted plots.
Establishment of recruited seedlings was ten-fold higher under cover of planted
trees than in grassy controls. Even pre-reproductive trees drew fruit-eating
birds and the seeds that they carried from nearby forest, and provided conditions
for establishment of shade-tolerant tree species. Overall, after 76 months of
cattle exclusion, 94% of the recruited shrubs and trees in experimental plots
were of species that we did not plant.
PMID- 25118609
TI - Role of genetics in pediatric inflammatory bowel disease.
AB - Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD), ulcerative
colitis (UC), and unclassified IBD, is characterized by chronic intestinal
inflammation and has a multifactorial etiology with complex interactions between
genetic and environmental factors. The genetics of IBD are believed to be common
and complex with over 163 associated genetic loci. However, the genetic
contribution of the majority of these common loci is small, and the effect sizes
are low. Although childhood onset IBD represents only 10% to 25% of all IBD
cases, in depth research into the genetic networks of pediatric IBD has revealed
exciting new developments and unsuspected pathways. Recent pediatric studies have
revealed an increasing spectrum of human monogenic diseases with high effect
sizes or penetrance that can present with IBD or IBD-like intestinal
inflammation. A substantial proportion of patients with these genetic defects
present with very early onset of intestinal inflammation, with onset of IBD at
less than 10 years of age. There is also considerable overlap with primary
immunodeficiencies and very early onset IBD. This review summarizes the current
understanding of the genetics of pediatric IBD with a focus on the very early
onset population and discusses the promising results from the effort of finding
missing heritability of IBD from studying pediatric population.
PMID- 25118610
TI - Magnesium retards the progress of the arterial calcifications in hemodialysis
patients: a pilot study.
AB - BACKGROUND: The aim of the study was to evaluate the impact of magnesium (Mg) on
the evolution of arterial calcifications in hemodialysis patients. PATIENTS AND
METHODS: Seventy-two stable hemodialysis patients were randomly allocated to two
groups: 36 administered a regimen containing magnesium carbonate plus calcium
acetate as a phosphate binder (Mg group), while the rest 36 received calcium
acetate alone (Ca group). The presence and the progression of arterial
calcifications were evaluated in plain X-rays using a simple vascular
calcification score. The duration of the follow-up period was 12 months. RESULTS:
Thirty-two patients of the Mg group and 27 of the Ca group completed the study.
The mean time average values of the biochemical laboratories did not differ
between the two groups, except serum Mg: 2.83 + 0.38 in the Mg group versus 2.52
+ 0.27 mg/dl in the Ca group, p = 0.001. In 9/32 (28.12 %) patients of the Mg
group and in 12/27 (44.44 %) patients of the Ca group, the arterial
calcifications were worsened, p = 0.276. Moreover, in 4/32 (15.6 %) patients of
the Mg group and in 0/27 (0 %) patients of the Ca group, they were improved, p =
0.040. The multivariate logistic regression analysis revealed that serum
magnesium was an independent predictor for no progression of the arterial
calcifications, p = 0.047. CONCLUSIONS: Magnesium probably retards the arterial
calcifications in hemodialysis patients. Further clinical studies are needed to
clarify whether magnesium provides cardiovascular protection to this group of
patients.
PMID- 25118611
TI - Beneficial dose conversion after switching from higher doses of shorter-acting
erythropoiesis-stimulating agents to C.E.R.A in CKD patients in clinical
practice: MINERVA Study.
AB - PURPOSE: To assess whether the correction dose recommended by the summary of
product characteristics was adequate and to confirm the adequacy of the
recommended conversion dosing strategies from shorter-acting erythropoiesis
stimulating agents (ESAs) to continuous erythropoietin receptor activator
(C.E.R.A) in anaemic chronic kidney disease (CKD) patients in the clinical
setting. METHODS: This was a 12-month, multicenter, prospective, observational
study in anaemic CKD patients on haemodialysis and not on dialysis receiving
C.E.R.A (at least one dose). RESULTS: A total of 227 patients were included (not
on dialysis; n = 142; haemodialysis: n = 85). The present analysis was conducted
on ESA-naive patients (not on dialysis: n = 31) and patients switched from other
ESA (not on dialysis: n = 63; haemodialysis: n = 57). Both on and not on dialysis
patients switched from other ESA received lower starting C.E.R.A doses than those
recommended, and remained stable during the 12-month period. The higher the
previous ESA dose was, the more beneficial the C.E.R.A dose conversion factor
was. The proportion of patients with stable haemoglobin within the target range
(11-13 g/dL) did not vary during the 12-month period both in nondialysis CKD
patients and in those undergoing dialysis [baseline: 42 (66.7 %) and 34 (59.6 %);
month 6: 21 (55.3 %) and 26 (50.0 %); month 12: 20 (64.5 %) and 25 (69.4 %),
respectively]. In naive patients, the mean weight-adjusted C.E.R.A dose during
the study (1.19 +/- 0.49 ug/kg/month) was similar to the recommended one. C.E.R.A
was well tolerated. CONCLUSIONS: Conversion from shorter-acting ESAs to C.E.R.A
doses lower than those recommended can efficiently maintain target haemoglobin
levels both in nondialysis and haemodialysis CKD patients, particularly when
switching from higher ESA doses. A monthly C.E.R.A dose of 1.2 ug/Kg seems
adequate for anaemia correction.
PMID- 25118613
TI - Septic complications and hospital admissions after transrectal ultrasound-guided
prostate biopsy: incidence rates and outcomes in 913 consecutive biopsies.
PMID- 25118612
TI - Protective effects of adiponectin on uncoupling of glomerular VEGF-NO axis in
early streptozotocin-induced type 2 diabetic rats.
AB - PURPOSE: To determine whether adiponectin could reduce microalbuminuria and
provide renal protective effects by improving endothelial dysfunction and
uncoupling of the glomerular vascular endothelial growth factor (VEGF)-nitric
oxide (NO) axis in streptozotocin-induced type 2 diabetic rats. METHODS: Wistar
rats were randomly divided into normal control group, diabetic nephropathy (DN)
group induced by high-fat feeding and streptozotocin, diabetic rats injected with
adenovirus-expressed adiponectin (AD-AdipoQ), and diabetic rats injected with AD
IRES-EGFP as control. Blood and urine samples were collected. Endothelium
dependent vasodilatation (EDV) of the aorta was measured. Renal tissues were
collected for CD34 immunohistochemistry. Glomerular NO and VEGF levels were
measured by the Griess reaction and Western blot testing, respectively. RESULTS:
Injections of AD-AdipoQ significantly increased serum adiponectin levels and
reduced the urinary albumin-to-creatinine ratio in diabetic rats (P < 0.05). The
levels of plasma glucose, serum insulin, high-sensitivity C-reactive protein, and
malondialdehyde were significantly reduced in diabetic rats after injections of
AD-AdipoQ (P < 0.05). Severe EDV impairment was observed in the DN group, which
was improved by AD-AdipoQ. CD34 expression in the glomeruli was also higher in
diabetic rats, indicating increased proliferation of glomerular endothelial
cells. However, AD-AdipoQ improved the increased proliferation of endothelial
cells in the glomeruli. Diabetic rats showed increased glomerular VEGF levels and
reduced NO levels. This uncoupling of the VEGF-NO axis was partially improved by
AD-AdipoQ. CONCLUSION: Adiponectin reduces the degree of microalbuminuria and has
renal protective effects by improving endothelial dysfunction and uncoupling of
the glomerular VEGF-NO axis in early diabetic nephropathy.
PMID- 25118601
TI - A comprehensive reference transcriptome resource for the common house spider
Parasteatoda tepidariorum.
AB - Parasteatoda tepidariorum is an increasingly popular model for the study of
spider development and the evolution of development more broadly. However, fully
understanding the regulation and evolution of P. tepidariorum development in
comparison to other animals requires a genomic perspective. Although research on
P. tepidariorum has provided major new insights, gene analysis to date has been
limited to candidate gene approaches. Furthermore, the few available EST
collections are based on embryonic transcripts, which have not been
systematically annotated and are unlikely to contain transcripts specific to post
embryonic stages of development. We therefore generated cDNA from pooled embryos
representing all described embryonic stages, as well as post-embryonic stages
including nymphs, larvae and adults, and using Illumina HiSeq technology obtained
a total of 625,076,514 100-bp paired end reads. We combined these data with
24,360 ESTs available in GenBank, and 1,040,006 reads newly generated from 454
pyrosequencing of a mixed-stage embryo cDNA library. The combined sequence data
were assembled using a custom de novo assembly strategy designed to optimize
assembly product length, number of predicted transcripts, and proportion of raw
reads incorporated into the assembly. The de novo assembly generated 446,427
contigs with an N50 of 1,875 bp. These sequences obtained 62,799 unique BLAST
hits against the NCBI non-redundant protein data base, including putative
orthologs to 8,917 Drosophila melanogaster genes based on best reciprocal BLAST
hit identity compared with the D. melanogaster proteome. Finally, we explored the
utility of the transcriptome for RNA-Seq studies, and showed that this resource
can be used as a mapping scaffold to detect differential gene expression in
different cDNA libraries. This resource will therefore provide a platform for
future genomic, gene expression and functional approaches using P. tepidariorum.
PMID- 25118615
TI - Current developments in pharmacogenomics of multiple sclerosis.
AB - Pharmacogenomics has a significant potential to impact how we treat diseases. It
involves targeting genetically identifiable populations with therapeutic
interventions that promises to yield immediate positive health outcomes with
lower or no side effects. The 'trial and error' method of treatment will no
longer be necessary with the successful implementation of personalized medicine.
The following is an overview of some new developments in pharmacogenomics of
multiple sclerosis, and how it has the potential to improve future treatment.
PMID- 25118614
TI - Expression of macrophage migration inhibitory factor in the mouse neocortex and
posterior piriform cortices during postnatal development.
AB - Macrophage migration inhibitory factor (MIF) functions as a pleiotropic protein,
participating in a vast array of cellular and biological processes. Abnormal
expression of MIF has been implicated in many neurological diseases, including
Parkinson's disease, epilepsy, Alzheimer's Disease, stroke, and neuropathic pain.
However, the expression patterns of mif transcript and MIF protein from the early
postnatal period through adulthood in the mouse brain are still poorly
understood. We therefore investigated the temporal and spatial expression of MIF
in the mouse neocortex during postnatal development in detail and partially in
posterior piriform cortices (pPC). As determined by quantitative real-time PCR
(qPCR), mif transcript gradually increased during development, with the highest
level noted at postnatal day 30 (P30) followed by a sharp decline at P75. In
contrast, Western blotting results showed that MIF increased constantly from P7
to P75. The highest level of MIF was at P75, while the lowest level of MIF was at
P7. Immunofluorescence histochemistry revealed that MIF-immunoreactive (ir) cells
were within the entire depth of the developed neocortex, and MIF was
heterogeneously distributed among cortical cells, especially at P7, P14, P30, and
P75; MIF was abundant in the pyramidal layer within pPC. Double immunostaining
showed that all the mature neurons were MIF-ir and all the intensely stained MIF
ir cells were parvalbumin positive (Pv +) at adult. Moreover, it was demonstrated
that MIF protein localized in the perikaryon, processes, presynaptic structures,
and the nucleus in neurons. Taken together, the developmentally regulated
expression and the subcellular localization of MIF should form a platform for an
analysis of MIF neurodevelopmental biology and MIF-related nerve diseases.
PMID- 25118616
TI - Hip dislocations after 2,734 elective unilateral fast-track total hip
arthroplasties: incidence, circumstances and predisposing factors.
AB - STUDY DESIGN: Retrospective review of prospectively collected data. OBJECTIVE: To
investigate the incidence of hip dislocation 90 days after total hip arthroplasty
in relation to time after surgery, mechanism of dislocation and predisposing
factors. METHODS: Prospective data on preoperative patient characteristics from
six Danish arthroplasty departments with similar fast-track approaches were cross
referenced with the Danish National Patient Registry for complete 90-day follow
up on readmissions, including emergency-room contacts. Complete patient files and
postoperative radiographs were reviewed in case of dislocations. Unadjusted
comparisons were made using t test/Chi-square analyses, while evaluation of risk
factors potentially predisposing to dislocations was done using uni- and
multivariate regression analysis. RESULTS: A total of 2,734 consecutive
unselected procedures were available for analysis, of which 65 (2.4 %) had
dislocations. Of these, eight were during index admission and five were treated
and discharged from the emergency room. Mechanisms of dislocation were most often
movement while supine or sitting for the first 30 days and due to
squatting/bending from day 31 to 90. The 65 patients with dislocations had
suboptimal cup placement in 34 (52.3 %), and a femoral head size of <36 mm in 20
(30.8 %) cases. Predisposing factors of dislocation were age >=75 [OR:1.96 (1.18
3.38)], pharmacologically treated psychiatric disease [OR:2.37 (1.29-4.36)] and
department of surgery [OR:2.27 (1.31-3.40)] but not hospital stay of <4 days.
Departments with recommendations for activity restrictions had fewer dislocations
than a department without restrictions. CONCLUSIONS: Patients >=75 years and with
pharmacologically treated psychiatric disease may be at increased risk of
dislocations after fast-track total hip arthroplasty. Further studies including
detailed information on patient and prosthesis characteristics, and activity
restrictions are needed to reduce the risk of dislocation.
PMID- 25118617
TI - An allosteric model of the inositol trisphosphate receptor with nonequilibrium
binding.
AB - The inositol trisphosphate receptor (IPR) is a crucial ion channel that regulates
the Ca(2+) influx from the endoplasmic reticulum (ER) to the cytoplasm. A
thorough study of the IPR channel contributes to a better understanding of
calcium oscillations and waves. It has long been observed that the IPR channel is
a typical biological system which performs adaptation. However, recent advances
on the physical essence of adaptation show that adaptation systems with a
negative feedback mechanism, such as the IPR channel, must break detailed balance
and always operate out of equilibrium with energy dissipation. Almost all
previous IPR models are equilibrium models assuming detailed balance and thus
violate the dissipative nature of adaptation. In this article, we constructed a
nonequilibrium allosteric model of single IPR channels based on the patch-clamp
experimental data obtained from the IPR in the outer membranes of isolated nuclei
of the Xenopus oocyte. It turns out that our model reproduces the patch-clamp
experimental data reasonably well and produces both the correct steady-state and
dynamic properties of the channel. Particularly, our model successfully describes
the complicated bimodal [Ca(2+)] dependence of the mean open duration at high
[IP3], a steady-state behavior which fails to be correctly described in previous
IPR models. Finally, we used the patch-clamp experimental data to validate that
the IPR channel indeed breaks detailed balance and thus is a nonequilibrium
system which consumes energy.
PMID- 25118619
TI - Laser desorption with corona discharge ion mobility spectrometry for direct
surface detection of explosives.
AB - We present a new highly sensitive technique for the detection of explosives
directly from the surface using laser desorption-corona discharge-ion mobility
spectrometry (LD-CD-IMS). We have developed LD based on laser diode modules (LDM)
and the technique was tested using three different LDM (445, 532 and 665 nm). The
explosives were detected directly from the surface without any further
preparation. We discuss the mechanism of the LD and the limitations of this
technique such as desorption time, transport time and desorption area. After the
evaluation of experimental data, we estimated the potential limits of detection
of this method to be 0.6 pg for TNT, 2.8 pg for RDX and 8.4 pg for PETN.
PMID- 25118618
TI - The effectiveness of interventions for ageing workers on (early) retirement, work
ability and productivity: a systematic review.
AB - PURPOSE: To systematically summarise the literature on the effects of
interventions for ageing workers that address work-related measures of
sustainable employability, i.e. (early) retirement, work ability and work
productivity. METHODS: A systematic review was performed by searching five
electronic databases for relevant studies published between January 1992 and
February 2014. Randomised controlled trials (RCTs) and quasi-experimental
intervention studies were included. The study population included workers aged
>=40 years, and the measured outcomes were positive indicators of labour force
participation, i.e. (early) retirement, work ability and work productivity. The
methodological quality of each included study was assessed, and best-evidence
synthesis was applied to draw conclusions about the evidence for the
effectiveness of each outcome. RESULTS: Four studies met the inclusion criteria.
The interventions were diverse and ranged from individual (e.g. exercise)
programmes to workplace programmes. Limited evidence for a favourable effect on
early retirement was found. Insufficient evidence was found for the remaining
outcomes, i.e. work ability and productivity, due to a lack of high-quality
studies and consistent findings. CONCLUSIONS: Insufficient and limited evidence
is available for a favourable effect of interventions to promote work-related
components of sustainable employability in ageing workers. This is due to a
scarcity of RCTs and inconsistent findings between the limited number of studies.
Additional intervention studies are needed to support evidence-based decision
making to prolong a healthy and productive working life for ageing workers.
PMID- 25118621
TI - Targeting the vasculature for cerebroprotection in the immature brain.
PMID- 25118622
TI - Joep MA Lange.
PMID- 25118620
TI - Noninvasive detection of sleep/wake changes and cataplexy-like behaviors in
orexin/ataxin-3 transgenic narcoleptic mice across the disease onset.
AB - Sleep and behavioral monitoring of young mice is necessary for understating the
progress of symptoms in congenital and acquired diseases associated with sleep
and movement disorders. In the current study, we have developed a non-invasive
sleep monitoring system that identifies wake and sleep patterns of newborn mice
using a simple piezoelectric transducer (PZT). Using this system, we have
succeeded in detecting age-dependent occurrences and changes in sleep
fragmentation of orexin/ataxin-3 narcoleptic mice (a narcoleptic mouse model with
postnatal hypocretin/orexin cell death) across the disease onset. We also
detected REM sleep/cataplexy patterns (i.e., immobility with clear heartbeat
[IMHB] signals due to the flaccid posture) by the PZT system, and found that
sudden onset of REM sleep-like episodes specifically occur in narcoleptic, but
not in wild type mice, suggesting that these episodes are likely cataplexy. In
contrast, gradual onset of IMHB likely reflects occurrence of REM sleep. In
summary, we have shown that the PZT system is useful as a non-invasive sleep and
behavior monitoring system to analyze the developmental aspects of sleep and
movement disorders in mice models.
PMID- 25118624
TI - Crossover from Josephson effect to single interface Andreev reflection in
asymmetric superconductor/nanowire junctions.
AB - We report on the fabrication and characterization of symmetric nanowire-based
Josephson junctions, that is, Al- and Nb-based junctions, and asymmetric
junctions employing superconducting Al and Nb. In the symmetric junctions, a
clear and pronounced Josephson supercurrent is observed. These samples also show
clear signatures of subharmonic gap structures. At zero magnetic field, a
Josephson coupling is found for the asymmetric Al/InAs-nanowire/Nb junctions as
well. By applying a magnetic field above the critical field of Al or by raising
the temperature above the critical temperature of Al the junction can be switched
to an effective single-interface superconductor/nanowire structure. In this
regime, a pronounced zero-bias conductance peak due to reflectionless tunneling
has been observed.
PMID- 25118623
TI - RAS mutations in benign epithelial tumors associated with BRAF inhibitor
treatment of melanoma.
PMID- 25118625
TI - Bioinformatics analysis of biomarkers and transcriptional factor motifs in Down
syndrome.
AB - In this study, biomarkers and transcriptional factor motifs were identified in
order to investigate the etiology and phenotypic severity of Down syndrome. GSE
1281, GSE 1611, and GSE 5390 were downloaded from the gene expression ominibus
(GEO). A robust multiarray analysis (RMA) algorithm was applied to detect
differentially expressed genes (DEGs). In order to screen for biological pathways
and to interrogate the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway
database, the database for annotation, visualization, and integrated discovery
(DAVID) was used to carry out a gene ontology (GO) function enrichment for DEGs.
Finally, a transcriptional regulatory network was constructed, and a
hypergeometric distribution test was applied to select for significantly enriched
transcriptional factor motifs. CBR1, DYRK1A, HMGN1, ITSN1, RCAN1, SON, TMEM50B,
and TTC3 were each up-regulated two-fold in Down syndrome samples compared to
normal samples; of these, SON and TTC3 were newly reported. CBR1, DYRK1A, HMGN1,
ITSN1, RCAN1, SON, TMEM50B, and TTC3 were located on human chromosome 21 (mouse
chromosome 16). The DEGs were significantly enriched in macromolecular complex
subunit organization and focal adhesion pathways. Eleven significantly enriched
transcription factor motifs (PAX5, EGR1, XBP1, SREBP1, OLF1, MZF1, NFY, NFKAPPAB,
MYCMAX, NFE2, and RP58) were identified. The DEGs and transcription factor motifs
identified in our study provide biomarkers for the understanding of Down syndrome
pathogenesis and progression.
PMID- 25118626
TI - Pulmonary hypertension due to acute respiratory distress syndrome.
AB - Our aims were to describe the prevalence of pulmonary hypertension in patients
with acute respiratory distress syndrome (ARDS), to characterize their
hemodynamic cardiopulmonary profiles, and to correlate these parameters with
outcome. All consecutive patients over 16 years of age who were in the intensive
care unit with a diagnosis of ARDS and an in situ pulmonary artery catheter for
hemodynamic monitoring were studied. Pulmonary hypertension was diagnosed when
the mean pulmonary artery pressure was >25 mmHg at rest with a pulmonary artery
occlusion pressure or left atrial pressure <15 mmHg. During the study period, 30
of 402 critically ill patients (7.46%) who were admitted to the ICU fulfilled the
criteria for ARDS. Of the 30 patients with ARDS, 14 met the criteria for
pulmonary hypertension, a prevalence of 46.6% (95% CI; 28-66%). The most common
cause of ARDS was pneumonia (56.3%). The overall mortality was 36.6% and was
similar in patients with and without pulmonary hypertension. Differences in
patients' hemodynamic profiles were influenced by the presence of pulmonary
hypertension. The levels of positive end-expiratory pressure and peak pressure
were higher in patients with pulmonary hypertension, and the PaCO2 was higher in
those who died. The level of airway pressure seemed to influence the onset of
pulmonary hypertension. Survival was determined by the severity of organ failure
at admission to the intensive care unit.
PMID- 25118627
TI - Associations between CD36 gene polymorphisms and susceptibility to coronary
artery heart disease.
AB - Associations between polymorphisms of the CD36 gene and susceptibility to
coronary artery heart disease (CHD) are not clear. We assessed allele frequencies
and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129
control patients using semi-quantitative polymerase chain reaction (PCR) and
restriction fragment length polymorphism (RFLP) analysis. Additionally, we
detected CD36 mRNA expression by real-time quantitative PCR, and we quantified
plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked
immunosorbent assay (ELISA). There were no significant differences between the
two groups (P>0.05) in allele frequencies of rs1761667 or in genotype
distribution and allele frequencies of rs3173798. The genotype distribution of
rs1761667 significantly differed between CHD patients and controls (P=0.034),
with a significantly higher frequency of the AG genotype in the CHD group
compared to the control group (P=0.011). The plasma levels of ox-LDL in patients
with the AG genotype were remarkably higher than those with the GG and AA
genotypes (P=0.010). In a randomized sample taken from patients in the two
groups, the CD36 mRNA expression of the CHD patients was higher than that of the
controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was
remarkably higher than in those with an AA genotype (P=0.005). After adjusted
logistic regression analysis, the AG genotype of rs1761667 was associated with an
increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the
rs1761667 polymorphism may be closely associated with developing CHD in the
Chongqing Han population of China, and an AG genotype may be a genetic
susceptibility factor for CHD.
PMID- 25118630
TI - Metabonomic analysis of the therapeutic effect of Potentilla discolor in the
treatment of type 2 diabetes mellitus.
AB - Type 2 diabetes mellitus (T2DM) is increased worldwide in parallel with the
obesity epidemic. Potentilla discolor is one of the most important crude
materials in Traditional Chinese medicine (TCM) for therapy of hyperglycemia and
hyperlipidemia. In this work, a plasma metabonomic approach based on the
combination of UPLC-Q-TOF with multivariate data analysis was applied to
investigate the therapeutic effects of the extract of P. discolor (EPD) and
corosolic acid (CA), the main bioactive compounds of P. discolor. Male C57BL/6
mice were fed with high-fat diet (HFD-fed group) for 8 weeks and then treated
with EPD (EPD-treated group) or CA (CA-treated group) for another 8 weeks. After
the experimental period, samples of plasma were collected and analyzed by ultra
performance liquid chromatography/quadrupole time of flight mass spectrometry
(UPLC-Q-TOF). The principal component analysis (PCA) and partial least squares
discriminant analysis (PLS-DA) models were built to find biomarkers of T2DM and
investigate the therapeutic effects of EPD and CA. 26 metabolites, which are
distributed in several metabolic pathways, were identified as potential
biomarkers of T2DM. It was found that EPD and CA could reverse the pathological
process of T2DM through regulating the disturbed pathway of metabolism. The
metabonomic results are beneficial not only for the evaluation of the therapeutic
effect of TCM but also for the elucidation of the underlying molecular mechanism.
PMID- 25118628
TI - Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth
factor increase vasculogenesis in ischemic rats.
AB - Administration or expression of growth factors, as well as implantation of
autologous bone marrow cells, promote in vivo angiogenesis. This study
investigated the angiogenic potential of combining both approaches through the
allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs)
expressing human basic fibroblast growth factor (hbFGF). After establishing a
hind limb ischemia model in Sprague Dawley rats, the animals were randomly
divided into four treatment groups: MSCs expressing green fluorescent protein
(GFP-MSC), MSCs expressing hbFGF (hbFGF-MSC), MSC controls, and phosphate
buffered saline (PBS) controls. After 2 weeks, MSC survival and differentiation,
hbFGF and vascular endothelial growth factor (VEGF) expression, and microvessel
density of ischemic muscles were determined. Stable hbFGF expression was observed
in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and
differentiated into vascular endothelial cells (P<0.001); however, their
differentiation rates were similar. Moreover, allogenic transplantation of hbFGF
MSCs increased VEGF expression (P=0.008) and microvessel density (P<0.001).
Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind
limb ischemia model by increasing the survival of transplanted cells that
subsequently differentiated into vascular endothelial cells. This study showed
the therapeutic potential of combining cell-based therapy with gene therapy to
treat ischemic disease.
PMID- 25118631
TI - Prostaglandin E2 levels and platelet function are different in cord blood
compared to adults.
AB - Neonatal platelets support primary haemostasis and thrombin generation as well as
adult platelets, despite observable hypoaggregability in vitro. High
prostaglandin E2 levels at accouchement could account for inhibited platelet
function via the EP4 receptor. We set out to determine prostaglandin E2 plasma
levels in cord blood of healthy neonates and evaluate the impact of prostaglandin
E2 on platelet function in adult and cord blood samples. Prostaglandin E2 plasma
levels were measured in cord blood and venous adult blood using GC-MS. Impact of
prostaglandin E2 on platelet aggregation was measured by spiking cord blood and
adult samples. Contributions of EP3 and EP4 receptors were evaluated using
respective antagonists. Intracellular cAMP concentrations were measured using a
commercial ELISA-kit. Prostaglandin E2 plasma levels were substantially higher in
cord blood than in adult samples. Spiking with prostaglandin E2 resulted in a
slight but consistent reduction of platelet aggregation in adult blood, but
response to PGE2 was blunted in cord blood samples. Aggregation response of
spiked adult samples was still higher than with non-spiked cord blood samples.
Blockage of EP4 receptors resulted in improved platelet aggregation in adult
platelets upon prostaglandin E2 spiking, while aggregation in cord blood samples
remained unaltered. Intracellular cAMP concentrations after preincubation with
prostaglandin E2 were only increased in adult samples. In conclusion, very high
prostaglandin E2 concentrations in cord blood affect platelet function. This
effect may partially explain neonatal platelet hypoaggregability. Peak levels of
prostaglandin E2 can potentially protect against birth stress-induced platelet
activation.
PMID- 25118632
TI - Hypnosis for induction of labour.
AB - BACKGROUND: Induction of labour using pharmacological and mechanical methods can
increase complications. Complementary and alternative medicine methods including
hypnosis may have the potential to provide a safe alternative option for the
induction of labour. However, the effectiveness of hypnosis for inducing labour
has not yet been fully evaluated. OBJECTIVES: To assess the effect of hypnosis
for induction of labour compared with no intervention or any other interventions.
SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
Register (31 January 2014), handsearched relevant conference proceedings,
contacted key personnel and organisations in the field for published and
unpublished references. SELECTION CRITERIA: All published and unpublished
randomised controlled trials (RCTs) and cluster-RCTs of acceptable quality
comparing hypnosis with no intervention or any other interventions, in which the
primary outcome is to assess whether labour was induced. DATA COLLECTION AND
ANALYSIS: Two review authors assessed the one trial report that was identified
(but was subsequently excluded). MAIN RESULTS: No RCTs or cluster-RCTs were
identified from the search strategy. AUTHORS' CONCLUSIONS: There was no evidence
available from RCTs to assess the effect of hypnosis for induction of labour.
Evidence from RCTs is required to evaluate the effectiveness and safety of this
intervention for labour induction. As hypnosis may delay standard care (in case
standard care is withheld during hypnosis), its use in induction of labour should
be considered on a case-by-case basis.Future RCTs are required to examine the
effectiveness and safety of hypnotic relaxation for induction of labour among
pregnant women who have anxiety above a certain level. The length and timing of
the intervention, as well as the staff training required, should be taken into
consideration. Moreover, the views and experiences of women and staff should also
be included in future RCTs.
PMID- 25118633
TI - Pathway deregulation and expression QTLs in response to Actinobacillus
pleuropneumoniae infection in swine.
AB - Actinobacillus (A.) pleuropneumoniae is among the most important pathogens in
pig. The agent causes severe economic losses due to decreased performance, the
occurrence of acute or chronic pleuropneumonia, and an increase in death
incidence. Since therapeutics cannot be used in a sustainable manner, and
vaccination is not always available, new prophylactic measures are urgently
needed. Recent research has provided evidence for a genetic predisposition in
susceptibility to A. pleuropneumoniae in a Hampshire * German Landrace F2 family
with 170 animals. The aim of the present study is to characterize the expression
response in this family in order to unravel resistance and susceptibility
mechanisms and to prioritize candidate genes for future fine mapping approaches.
F2 pigs differed distinctly in clinical, pathological, and microbiological
parameters after challenge with A. pleuropneumoniae. We monitored genome-wide
gene expression from the 50 most and 50 least susceptible F2 pigs and identified
171 genes differentially expressed between these extreme phenotypes. We combined
expression QTL analyses with network analyses and functional characterization
using gene set enrichment analysis and identified a functional hotspot on SSC13,
including 55 eQTL. The integration of the different results provides a resource
for candidate prioritization for fine mapping strategies, such as TF, TFRC,
RUNX1, TCN1, HP, CD14, among others.
PMID- 25118634
TI - Modelling age-related metabolic disorders in the mouse.
AB - Ageing can be characterised by a general decline in cellular function, which
affects whole-body homoeostasis with metabolic dysfunction-a common hallmark of
ageing. The identification and characterisation of the genetic pathways involved
are paramount to the understanding of how we age and the development of
therapeutic strategies for combating age-related disease. Furthermore, in
addition to understanding the ageing process itself, we must understand the
interactions ageing has with genetic variation that results in disease
phenotypes. The use of model systems such as the mouse, which has a relatively
short lifespan, rapid reproduction (resulting in a large number of offspring),
well-characterised biology, a fully sequenced genome, and the availability of
tools for genetic manipulation is essential for such studies. Here we review the
relationship between ageing and metabolism and highlight the need for modelling
these processes.
PMID- 25118635
TI - A stem cell medium containing neural stimulating factor induces a pancreatic
cancer stem-like cell-enriched population.
AB - Cancer stem cells (CSCs) have been studied for their self-renewal capacity and
pluripotency, as well as their resistance to anticancer therapy and their ability
to metastasize to distant organs. CSCs are difficult to study because their
population is quite low in tumor specimens. To overcome this problem, we
established a culture method to induce a pancreatic cancer stem-like cell (P
CSLC)-enriched population from human pancreatic cancer cell lines. Human
pancreatic cancer cell lines established at our department were cultured in CSC
inducing media containing epidermal growth factor (EGF), basic fibroblast growth
factor (bFGF), leukemia inhibitory factor (LIF), neural cell survivor factor-1
(NSF-1), and N-acetylcysteine. Sphere cells were obtained and then transferred to
a laminin-coated dish and cultured for approximately two months. The surface
markers, gene expression, aldehyde dehydrogenase (ALDH) activity, cell cycle, and
tumorigenicity of these induced cells were examined for their stem cell-like
characteristics. The population of these induced cells expanded within a few
months. The ratio of CD24high, CD44high, epithelial specific antigen (ESA) high,
and CD44variant (CD44v) high cells in the induced cells was greatly enriched. The
induced cells stayed in the G0/G1 phase and demonstrated mesenchymal and stemness
properties. The induced cells had high tumorigenic potential. Thus, we
established a culture method to induce a P-CSLC-enriched population from human
pancreatic cancer cell lines. The CSLC population was enriched approximately 100
fold with this method. Our culture method may contribute to the precise analysis
of CSCs and thus support the establishment of CSC-targeting therapy.
PMID- 25118637
TI - Tavaborole: first global approval.
AB - Tavaborole is a novel, low-molecular weight oxaborole antifungal drug under
development by Anacor Pharmaceuticals Inc. for the topical treatment of
onychomycosis of the toenail. The drug has received its first global approval for
this indication in the US. This article summarizes the milestones in the
development of tavaborole leading to this first approval for onychomycosis of the
toenails.
PMID- 25118636
TI - Nasal chondromesenchymal hamartomas arise secondary to germline and somatic
mutations of DICER1 in the pleuropulmonary blastoma tumor predisposition
disorder.
AB - Nasal chondromesenchymal hamartoma (NCMH) is a rare nasal tumor that typically
presents in young children. We previously reported on NCMH occurrence in children
with pleuropulmonary blastoma (PPB), a rare pulmonary dysembryonic sarcoma that
is the hallmark neoplasm in the PPB-associated DICER1 tumor predisposition
disorder. Original pathologic materials from individuals with a PPB, PPB
associated tumor and/or a DICER1 mutation were centrally reviewed by the
International PPB Registry. Paraffin-embedded NCMH tumor tissue was available in
three cases. Laser-capture microdissection was used to isolate mesenchymal
spindle cells and cartilage in one case for Sanger sequencing of DICER1. Nine
patients (5F/4M) had PPB and NCMH. NCMH was diagnosed at a median age of 10 years
(range 6-21 years). NCMH developed 4.5-13 years after PPB. Presenting NCMH
symptoms included chronic sinusitis and nasal congestion. Five patients had
bilateral tumors. Local NCMH recurrences required several surgical resections in
two patients, but all nine patients were alive at 0-16 years of follow-up.
Pathogenic germline DICER1 mutations were found in 6/8 NCMH patients tested. In 2
of the patients with germline DICER1 mutations, somatic DICER1 missense mutations
were also identified in their NCMH (E1813D; n = 2). Three additional PPB patients
developed other nasal lesions seen in the general population (a Schneiderian
papilloma, chronic sinusitis with cysts, and allergic nasal polyps with
eosinophils). Two of these patients had germline DICER1 mutations. Pathogenic
germline and somatic mutations of DICER1 in NCMH establishes that the genetic
etiology of NCMH is similar to PPB, despite the disparate biological potential of
these neoplasms.
PMID- 25118639
TI - [Subcutaneous emphysema following non-surgical peri-implantitis therapy using an
air abrasive device: a case report].
AB - Subcutaneous emphysema are rare complications in periodontology. In most cases,
they resolve spontaneously. However, air might disperse into deeper facial spaces
causing life-threatening complications such as compression of the
tracheobronchial tree or the development of pneumomediastinum. Moreover,
microorganisms might spread from the oral cavity into deeper spaces. Hence, rapid
diagnosis of subcutaneous emphysema is important. Characteristic signs are both a
shiftable swelling and a crepitation. In this case report, the case of a 69-year
old man with a subcutaneous emphysema immediately after peri-implantitis therapy
with the use of a glycine-based powder air-polishing device is described.
Following therapy, air accumulated in the left side of the face. Seven days after
non-surgical peri-implantitis therapy, the patient was asymptomatic with complete
resolution of the emphysema.
PMID- 25118638
TI - Locally-delivered T-cell-derived cellular vehicles efficiently track and deliver
adenovirus delta24-RGD to infiltrating glioma.
AB - Oncolytic adenoviral vectors are a promising alternative for the treatment of
glioblastoma. Recent publications have demonstrated the advantages of shielding
viral particles within cellular vehicles (CVs), which can be targeted towards the
tumor microenvironment. Here, we studied T-cells, often having a natural capacity
to target tumors, for their feasibility as a CV to deliver the oncolytic
adenovirus, Delta24-RGD, to glioblastoma. The Jurkat T-cell line was assessed in
co-culture with the glioblastoma stem cell (GSC) line, MGG8, for the optimal
transfer conditions of Delta24-RGD in vitro. The effect of intraparenchymal and
tail vein injections on intratumoral virus distribution and overall survival was
addressed in an orthotopic glioma stem cell (GSC)-based xenograft model. Jurkat T
cells were demonstrated to facilitate the amplification and transfer of Delta24
RGD onto GSCs. Delta24-RGD dosing and incubation time were found to influence the
migratory ability of T-cells towards GSCs. Injection of Delta24-RGD-loaded T
cells into the brains of GSC-bearing mice led to migration towards the tumor and
dispersion of the virus within the tumor core and infiltrative zones. This
occurred after injection into the ipsilateral hemisphere, as well as into the non
tumor-bearing hemisphere. We found that T-cell-mediated delivery of Delta24-RGD
led to the inhibition of tumor growth compared to non-treated controls, resulting
in prolonged survival (p = 0.007). Systemic administration of virus-loaded T
cells resulted in intratumoral viral delivery, albeit at low levels. Based on
these findings, we conclude that T-cell-based CVs are a feasible approach to
local Delta24-RGD delivery in glioblastoma, although efficient systemic targeting
requires further improvement.
PMID- 25118640
TI - Primary sleeve gastrectomy compared to sleeve gastrectomy as revisional surgery:
weight loss and complications at intermediate follow-up.
AB - INTRODUCTION: The laparoscopic adjustable gastric band (LAGB) can be revised to
sleeve gastrectomy (LSG) for various reasons. Data are limited on the safety and
efficacy of single-stage removal of LAGB and creation of LSG. METHODS: A
retrospective review of cases was performed from 2010 to 2013. From the primary
LSG group, a control group was matched in a 2:1 ratio. RESULTS: Thirty-two
patients underwent single-stage revision from LAGB to LSG, with a control group
of 64. The most common indication for revision was insufficient weight loss
(62.5%). Operative time for revision and control groups was 134 and 92 min,
respectively (p < 0.0001). Hospital stay was 3.22 and 2.59 days, respectively (p
= 0.02). Overall, the 30-day complication rate for revision and control patients
was 14.71 and 6.25%, respectively (p = 0.20). There were no leaks, one stricture
(3.13%) in the revision group, and one reoperation for bleeding in the control
group (1.56%). For patients with BMI >30 at surgery, change in BMI at 12 months
for revision and control was 8.77 and 11.58, respectively (p = 0.02). CONCLUSION:
Single-stage revision can be performed safely, with minimal increases in hospital
stay and 30-day complications. Weight loss is greater in those who undergo
primary LSG compared to those who undergo LSG as revision.
PMID- 25118641
TI - Retroperitoneal unicentric Castleman's disease-a hyaline vascular challenge.
AB - Castleman's disease is a rare lymphoproliferative disorder. Multiple variants of
the disease exist, with differentiation based on tissue pathology and number of
masses within the body. We present the medical diagnostic and surgical treatment
pathway of a retroperitoneal unicentric hyaline vascular variant complicated by
close proximity to major vascular structures.
PMID- 25118642
TI - Importance of lymph node involvement in pancreatic neuroendocrine tumors: impact
on survival and implications for surgical resection.
AB - BACKGROUND: Conflicting data exist on predictors of nodal metastases and their
impact on survival in patients with pancreatic neuroendocrine tumors (PNETs). We
aim to identify factors associated with lymph node involvement and evaluate the
effect of nodal metastases on survival. METHODS: All patients undergoing surgery
for PNETs in the Surveillance, Epidemiology, and End Results (SEER) tumor
registry from 1988 to 2010 were included. Predictors of lymph node involvement
and disease-specific survival (DSS) were evaluated using logistic regression and
Cox regression, respectively. RESULTS: Patients (1,915) underwent surgery for a
PNET (62% nonfunctional). Nodal positivity was associated with increasing tumor
size (p < 0.001) and grade (p < 0.001). Unadjusted DSS at 5 years was 81% for N0,
74 for Nx, and 69% for N1, respectively, (p < 0.001). After adjustment for tumor
size and grade, DSS was significantly decreased in N1 patients (HR 1.57; 95% CI
1.23-1.95). For patients who had at least one node examined and had low-grade
PNETs <1 cm, no nodal metastases were found. CONCLUSIONS: High tumor grade and
increasing size predict nodal metastases in patients with PNETs. N1 status is
independently associated with decreased DSS. Low-grade tumors <1 cm may be
observed or enucleated.
PMID- 25118643
TI - Endoscopy in the early postoperative setting after primary gastrointestinal
anastomosis.
AB - INTRODUCTION: Gastrointestinal anastomoses may require early evaluation and
treatment via flexible endoscopic techniques when complications arise. There is
reticence, however, to perform endoscopy given the applied mechanical forces. We
aimed to identify the incidence of gastrointestinal anastomotic perforation or
disruption resulting from endoscopy performed <=6 weeks of anastomoses. METHODS:
Review of patients from 2002 to 2013 who underwent flexible endoscopy within 6
weeks of creation of gastrointestinal anastomosis. Exclusion criteria included
intraoperative endoscopy, anastomotic perforation prior to endoscopy, and
endoscopy remote from the anastomotic site. Data are presented as median
(interquartile range; IQR) or percentages as appropriate. RESULTS: Twenty-four
patients met our criteria (age 69 years [IQR 54-77], 54% men]). Endoscopy was
performed at a median postoperative time of 18 days (IQR 8-30). Indications for
endoscopy included bleeding (66%), obstruction (13%), pain (13%), concern for
pancreatic duct leak (4%), and concern for ischemia (4%). Six patients underwent
therapeutic endoscopic procedures including coagulation (8%), balloon dilation
(8%), tube decompression (8%), and stent placement (4%). There were no
anastomotic perforations or disruptions as a result of endoscopy. CONCLUSION:
Despite theoretical risks of adverse events of flexible endoscopy in the early
postoperative period, no endoscopic perforations or disruptions occurred in
recently created surgical anastomoses.
PMID- 25118644
TI - Surgeon volume plays a significant role in outcomes and cost following open
incisional hernia repair.
AB - TITLE: Surgeon Volume Plays a Significant Role in Outcomes and Cost Following
Open Incisional Hernia Repair PURPOSE: Incisional hernia is a common complication
following gastrointestinal surgery. Many surgeons elect to perform incisional
hernia repairs despite performing only limited numbers of hernia repairs
annually. This study examines the relationship between surgeon/facility volume
and operative time, reoperation rates, and cost following initial open hernia
repair. METHODS: The New York Statewide Planning and Research Cooperative System
was queried for elective open initial incisional hernias repairs from 2001 to
2006. Surgeon/facility volumes were calculated as mean number of open incisional
hernia repairs per year from 2001 to 2006. Reoperations for recurrent hernia over
a 5-year period were identified using ICD-9/CPT codes. Multivariable regression
was used to compare patient, surgeon, and facility characteristics with operative
time, hernia reoperation, and hospital charges. RESULTS: Eighteen thousand forty
seven patients met the inclusion criteria. The hernia reoperation rate was 9%,
and median time to reoperation was 1.4 years (mean = 1.8). After adjusting for
clinical factors, surgeons performing an average of >=36 repairs/year had
significantly lower reoperation rates (HR = 0.59, 95% confidence interval (CI) =
0.48,0.72), operative time (incidence rate ratio (IRR) = 0.67, 95% CI =
0.64,0.71), and downstream charges (IRR = 0.63, 95% CI = 0.57,0.69). Facility
characteristics (volume, academic affiliation, location) were not associated with
reoperation. CONCLUSIONS: This study found a strong association between
individual surgeon incisional hernia repair volume and hernia reoperation rates,
operative efficiency, and charges. Preferential referral to high-volume surgeons
may lead to improved outcomes and lower costs.
PMID- 25118647
TI - In silico analysis of different generation beta lactams antibiotics with
penicillin binding protein-2 of Neisseria meningitidis for curing meningococcal
disease.
AB - Neisseria meningitidis is a gram negative, diplococcic pathogen responsible for
the meningococcal disease and fulminant septicemia. Penicillin-binding proteins-2
(PBPs) is crucial for the cell wall biosynthesis during cell proliferation of N.
meningitidis and these are the target for beta-lactam antibiotics. For many years
penicillin has been recognized as the antibiotic for meningococcal disease but
the meningococcus has seemed to be antibiotic resistance. In the present work we
have verified the molecular interaction of Penicillin binding protein-2 N.
meningitidis to different generation of beta-lactam antibiotics and concluded
that the third generation of beta-lactam antibiotics shows efficient binding with
Penicillin binding protein-2 of N. meningitidis. On the basis of binding
efficiency and inhibition constant, ceftazidime emerged as the most efficient
antibiotic amongst the other advanced beta-lactam antibiotics against Penicillin
binding protein-2 of N. meningitidis.
PMID- 25118648
TI - PDB explorer -- a web based algorithm for protein annotation viewer and 3D
visualization.
AB - The PDB file format, is a text format characterizing the three dimensional
structures of macro molecules available in the Protein Data Bank (PDB).
Determined protein structure are found in coalition with other molecules or ions
such as nucleic acids, water, ions, Drug molecules and so on, which therefore can
be described in the PDB format and have been deposited in PDB database. PDB is a
machine generated file, it's not human readable format, to read this file we need
any computational tool to understand it. The objective of our present study is to
develop a free online software for retrieval, visualization and reading of
annotation of a protein 3D structure which is available in PDB database. Main aim
is to create PDB file in human readable format, i.e., the information in PDB file
is converted in readable sentences. It displays all possible information from a
PDB file including 3D structure of that file. Programming languages and scripting
languages like Perl, CSS, Javascript, Ajax, and HTML have been used for the
development of PDB Explorer. The PDB Explorer directly parses the PDB file,
calling methods for parsed element secondary structure element, atoms,
coordinates etc. PDB Explorer is freely available at
http://www.pdbexplorer.eminentbio.com/home with no requirement of log-in.
PMID- 25118646
TI - Overexpression of oxidored-nitro domain containing protein 1 induces growth
inhibition and apoptosis in human prostate cancer PC3 cells.
AB - Previous studies have reported that oxidored-nitro domain containing protein 1
(NOR1) is a novel tumor suppressor gene identified in various types of cancer,
such as nasopharyngeal carcinoma and cervical cancer. Recent studies have shown
that NOR1 expression is lower in prostate cancer compared with normal prostate
tissue. However, the specific function and exact mechanism of NOR1 in prostate
cancer remains to be clarified. The present study aimed to investigate the
function and mechanism of NOR1 in prostate cancer PC3 cells. DU145 and PC3 cells
were transduced with a vector and cell viability, proliferation and apoptosis
were determined. As predicted, NOR1 overexpression significantly inhibited growth
and apoptosis in PC3 cells. NOR1 overexpression decreased the expression of the
anti-apoptotic genes Bcl-2 and Bcl-xl and increased the level of the pro
apoptotic genes Bax and Bak in PC3 cells. Further investigation demonstrated that
NOR1 overexpression activates caspase-3. Silencing of NOR1 did not inhibit growth
or induce apoptosis in PC3 cells. Moreover, NOR1 inhibited proliferation and
induced apoptosis via the activation of MAPK. The overexpression of NOR1
significantly inhibited tumor growth in PC3 tumor-bearing nude mice. The results
suggest that the upregulated NOR1 expression was able to inhibit the progression
of prostate cancer. Thus, NOR1 may be an ideal target for the treatment of
prostate cancer.
PMID- 25118649
TI - Molecular docking studies of curcumin natural derivatives with DNA topoisomerase
I and II-DNA complexes.
AB - DNA topoisomerase I (topo I) and II (topo II) are essential enzymes that solve
the topological problems of DNA by allowing DNA strands or double helices to pass
through each other during cellular processes such as replication, transcription,
recombination, and chromatin remodeling. Their critical roles make topoisomerases
an attractive drug target against cancer. The present molecular docking study
provides insights into the inhibition of topo I and II by curcumin natural
derivatives. The binding modes suggested that curcumin natural derivatives docked
at the site of DNA cleavage parallel to the axis of DNA base pairing.
Cyclocurcumin and curcumin sulphate were predicted to be the most potent
inhibitors amongst all the curcumin natural derivatives docked. The binding modes
of cyclocurcumin and curcumin sulphate were similar to known inhibitors of topo I
and II. Residues like Arg364, Asn722 and base A113 (when docked to topo I-DNA
complex) and residues Asp479, Gln778 and base T9 (when docked to topo II-DNA
complex) seem to play important role in the binding of curcumin natural
derivatives at the site of DNA cleavage.
PMID- 25118650
TI - Mis-sesnse mutations in Tafazzin (TAZ) that escort to mild clinical symptoms of
Barth syndrome is owed to the minimal inhibitory effect of the mutations on the
enzyme function: In-silico evidence.
AB - Tafazzin (EC 2.3.1.23) is a Phospholipid Transacylase involved in Cardiolipin
remodeling on mitochondrial membrane and coded by TAZ gene (Cytogenetic Location:
Xq28) in human. Its mutations cause Barth syndrome (MIM ID: #302060)/3-Methyl
Glutaconyl Aciduria Type II, an inborn error of metabolism often leading to
foetal or infantile fatality. Nevertheless, some mis-sense mutations result in
mild clinical symptoms. To evaluate the rationale of mild symptoms and for an
insight of Tafazzin active site, sequence based and structure based ramifications
of wild and mutant Tafazzins were compared in-silico. Sequence based domain
predictions, surface accessibilities on substitution & conserved catalytic sites
with statistical drifts, as well as thermal stability changes for the mutations
and the interaction analysis of Tafazzin were performed. Crystal structure of
Tafazzin is not yet resolved experimentally, therefore 3D coordinates of Tafazzin
and its mutants were spawned through homology modeling. Energetically minimized
and structurally validated models were used for comparative docking simulations.
We analyzed active site geometry of the models in addition to calculating overall
substrate binding efficiencies for each of the enzyme-ligand complex deduced from
binding energies instead of comparing only the docking scores. Also, individual
binding energies of catalytic residues on conserved HX4D motif of Acyltransferase
superfamily present in Tafazzins were estimated. This work elucidates the basis
of mild symptoms in patients with mis-sense mutations, identifies the most
pathogenic mutant among others in the study and also divulges the critical role
of HX4D domain towards successful transacylation by Taffazin. The in-silico
observations are in complete agreement with clinical findings reported for the
patients with mutations.
PMID- 25118651
TI - An enzoinformatics study for prediction of efficacies of three novel penem
antibiotics against New Delhi metallo-beta-lactamase-1 bacterial enzyme.
AB - New Delhi metallo-beta-lactamase (NDM-1) is a beta-lactamase (class B
carbapenemase) containing Zn2+ and other divalent cations as cofactors which
possesses the ability to inactivate all beta lactams (including carbapenems)
except aztreonam by catalyzing the hydrolytic cleavage of the substrate amide
bond. Carbapenemases are either serine enzymes or metallo-beta-lactamases (MBLs)
that utilize at least one zinc ion for hydrolysis. The present study describes
the molecular interaction of carbapenems (Imipenem, Meropenem, Ertapenem,
Doripenem, Panipenem, Biapenem, Razupenem, Faropenem, Tebipenem and Tomopenem)
with NDM-1, beta-lactamase enzyme. Docking between NDM-1 and each of these
carbapenems (separately) was performed using 'Autodock4.2'.
PMID- 25118645
TI - The burden of HPV-associated anogenital cancers.
AB - The epidemiology of anogenital cancers is under going substantial change.
Cervical cancer remains a major public health concern, particular in resource
limited settings. Cancers of the anus, penis, vagina and vulva are relatively
uncommon cancers, but may be increasing in incidence. The change in occurrence of
anogenital cancers may be due to increasing HPV transmission secondary to changes
in sexual behaviour. Screening programmes and the HPV vaccine offer optimism that
anogenital cancers can be prevented. This article reviews the epidemiology of
anogenital cancers with a focus on Scottish data.
PMID- 25118652
TI - Performance evaluation of Warshall algorithm and dynamic programming for Markov
chain in local sequence alignment.
AB - Markov Chain is very effective in prediction basically in long data set. In DNA
sequencing it is always very important to find the existence of certain
nucleotides based on the previous history of the data set. We imposed the Chapman
Kolmogorov equation to accomplish the task of Markov Chain. Chapman Kolmogorov
equation is the key to help the address the proper places of the DNA chain and
this is very powerful tools in mathematics as well as in any other prediction
based research. It incorporates the score of DNA sequences calculated by various
techniques. Our research utilize the fundamentals of Warshall Algorithm (WA) and
Dynamic Programming (DP) to measures the score of DNA segments. The outcomes of
the experiment are that Warshall Algorithm is good for small DNA sequences on the
other hand Dynamic Programming are good for long DNA sequences. On the top of
above findings, it is very important to measure the risk factors of local
sequencing during the matching of local sequence alignments whatever the length.
PMID- 25118653
TI - In silico analysis for five major cereal crops phytocystatins.
AB - Five major cereal crops like rice, wheat, maize, barley and sorghum are
continuously threatened by a multitude of pathogens and other disorders.
Cystatins offers a pivotal role in deciding the promising plant response. The use
of bioinformatics tools for phylogenetic relationships of five major cereal crops
(rice, wheat, maize, barley and sorghum) phytocystatins based on amino acid
sequence information was elucidated and their secondary and tertiary structures
were investigated for structural comparisons. Twenty eight distinct
phytocystatins from 28 plant species were investigated. Phytocystatins could be
divided into five distinct phylogenetic groups. Five major cereal crops their
structural features were highly conserved their amino acid sequence similarities
ranged from 48 to 86%. A new highly conserved amino acid sequence motif,
YEAKxWxKxF, in the C-terminal end being unique to phytocystatins was identified.
The predicted 3D homology models showed a high conservation of the general
central structure of the phytocystatins i.e. the 4-5 anti-parallel beta-sheets,
wrapping halfway round a single central alpha-helix and particularly the three
active site regions, the N-terminal, the 1st and 2nd hairpin loops. Any
structural differences seem to be mainly in the length of the N and C terminal,
the length of the 2nd hairpin loop and the 5th beta-sheet. Via docking
experiments, small heterogeneities were observed in the vicinity of the OC-I
active sites that seemed to be influential in the binding process and stability
of the resultant inhibitor-protease complex.
PMID- 25118654
TI - Effects of bridge functions on radial distribution functions of liquid water.
AB - In this report the radial distribution functions (RDFs) of liquid water are
calculated on the basis of the classical density functional theory combined with
the reference interaction site model for molecular liquids. The bridge functions,
which are neglected in the hypernetted-chain (HNC) approximation, are taken into
account through the density expansion for the Helmholtz free energy functional up
to the third order. A factorization approximation to the ternary direct
correlation functions in terms of the site-site pair correlation functions is
then employed in the expression of the bridge functions, thus leading to a closed
set of integral equations for the determination of the RDFs. It is confirmed
through numerical calculations that incorporation of the oxygen-oxygen bridge
function substantially improves the poor descriptions by the HNC approximation at
room temperature, e.g., for the second peak of the oxygen-oxygen RDF.
PMID- 25118656
TI - {RuNO}(6)vs. co-ligand oxidation: two non-innocent groups in one ruthenium
nitrosyl complex.
AB - Recently, a new {RuNO}(6) complex, [Ru(L)(PPh3)(NO)(Cl)](2+) (where L = 1-phenyl
1-(pyridin-2-yl)-2-(pyridin-2-ylmethylene)hydrazine), was reported which exhibits
a one-electron quasireversible oxidation. The oxidized product,
[Ru(L)(PPh3)(NO)(Cl)](3+), was isolated and proposed to be a highly unusual
{RuNO}(5) complex. In this paper, we investigate the electronic structure of both
of these ruthenium complexes by DFT calculations and find that the oxidized
species is best described as a {RuNO}(6) complex with a co-ligand radical.
[Ru(L)(PPh3)(NO)(Cl)](2+) is therefore oxidized to [Ru(L(+))(PPh3)(NO)(Cl)](3+),
i.e. this is an interesting example of a complex with two non-innocent ligands
simultaneously bound to a ruthenium center.
PMID- 25118657
TI - Does guideline knowledge affect treatment compliance among emergency doctors?
AB - BACKGROUND: The insufficient adoption of internationally accepted clinical
guidelines may lead to less than adequate patient care of patients with asthma.
OBJECTIVE: To evaluate the knowledge and treatment compliance with Global
Initiative of Asthma (GINA, 2011) asthma treatment guidelines among emergency
physicians (EPs) at a referral hospital in northern Malaysia. METHODS: A cross
sectional study was designed in the territory-level referral hospital in northern
Malaysia. Twenty-seven EPs were asked to complete an asthma guideline
questionnaire to assess their knowledge regarding GINA 2011 asthma treatment
guidelines. A total of 810 patients were enrolled, and 30 patients were selected
per physician. The authors evaluated the physicians' compliance with GINA 2011
asthma treatment guidelines. RESULTS: Of 27 EPs, 20 (74.1%) had adequate
knowledge of GINA 2011 asthma treatment guidelines. A total of 615 (75.9%)
patients received guideline-recommended emergency treatment. Shortness of breath
(n = 436, 53.8%) was the most frequently reported chief complaint. Furthermore,
there was a significant but weak association between knowledge of the guideline
and treatment compliance among emergency doctors (P = 0.003, phi = 0.110).
Moreover, there was no significant change in therapy for patients with comorbid
conditions. The mean age of respondents was 27.3 years. CONCLUSIONS: Overall, a
fair level of guideline knowledge and treatment compliance was noted among EPs.
Doctors with adequate guideline knowledge were more likely to comply with GINA
2011 asthma treatment guidelines.
PMID- 25118655
TI - Identification and characterization of alkaline protease producing Bacillus
firmus species EMBS023 by 16S rRNA gene sequencing.
AB - Probiotic microorganisms are those which exert a positive exect on the growth of
the host, when administered as a dietary mixture in an adequate amount. They form
the best alternative to the use of antibiotics for controlling enteric diseases
in poultry farm animals, especially in the light of the gruesome problems of
development of antibiotic resistance in enteric pathogens and the contamination
of poultry products with antibiotics. 16S rDNA sequencing which has gained wide
popularity amongst microbiologists for the molecular characterization and
identification of newly discovered isolates provides accurate identification of
isolates down to the level of sub-species (strain). It's most important advantage
over the traditional biochemical characterization methods are that it can provide
an accurate identification of strains with atypical phenotypic characters as
well. The following work is an application of 16S rRNA gene sequencing approach
to identify a novel, alkaline protease producing bacteria, from poultry farm
waste. The sample was collected from a local poultry farm in the Guntur district,
Andhra Pradesh, India. Subsequently the sample was serially diluted and the
aliquots were incubated for a suitable time period following which the suspected
colony was subjected to 16S rDNA sequencing. The results showed the isolate to be
a novel, high alkaline protease producing bacteria, which was named Bacillus
firmus isolate EMBS023, after characterization the sequence of isolate was
deposited in GenBank with accession number JN990980.
PMID- 25118658
TI - Physiological measurements using ultra-high field fMRI: a review.
AB - Functional MRI (fMRI) has grown to be the neuroimaging technique of choice for
investigating brain function. This topical review provides an outline of fMRI
methods and applications, with a particular emphasis on the recent advances
provided by ultra-high field (UHF) scanners to allow functional mapping with
greater sensitivity and improved spatial specificity. A short outline of the
origin of the blood oxygenation level dependent (BOLD) contrast is provided,
followed by a review of BOLD fMRI methods based on gradient-echo (GE) and spin
echo (SE) contrast. Phase based fMRI measures, as well as perfusion contrast
obtained with the technique of arterial spin labelling (ASL), are also discussed.
An overview of 7 T based functional neuroimaging is provided, outlining the
potential advances to be made and technical challenges to be addressed.
PMID- 25118659
TI - 1-calcium phosphate-uracil, a synthesized pyrimidine derivative agent, has anti
proliferative, pro-apoptotic and anti-invasion effects on multiple tumor cell
lines.
AB - 1-calcium phosphate-uracil (1-CP-U), a synthetic pyrimidine derivative, has been
documented to demonstrate a variety of different biological activities. However,
the potency and mechanisms of this agent's anti-cancer activity have not been
elucidated to date. In the present study, the anti-cancer effects of 1-CP-U were
examined in a range of in vitro assays. Different cell lines were treated with 1
CP-U at varied concentrations (0.7, 1.0, 1.4 umol/l) for indicated durations. The
cell proliferation was then examined by MTT assay. The cellular apoptotic effects
were detected by Hoechst 33342 and Annexin V/propidium iodide staining, while the
capacity of 1-CP-U on invasion and migration were examined by cell invasion and
wound healing assays. The expression of matrix metalloproteinase proteins, as
well as pro- and antiapoptotic proteins was detected by western blotting
analysis. The results identified that 1-CP-U was able to inhibit the viability of
SKOV3, HeLa, SMMC-7721 and A549 cell lines in a dose- and time-dependent manner,
while it exerted only marginal toxic effects on non-cancerous cells. The IC50
concentration of 1-CP-U for tumor cell lines was ~1.0 umol/l. The growth
inhibition induced by 1-CP-U was accompanied by a broad spectrum of pro-apoptotic
activities, in which different cell lines varied in their sensitivity to 1-CP-U.
Meanwhile, the increased expression of the pro-apoptotic protein B-cell lymphoma
2 (Bcl-2)-associated X and a marked reduction of Bcl-2 levels were associated
with increased 1-CP-U concentrations. Additionally, anti-migration and anti
invasion effects of 1-CP-U were evidently associated with the downregulation of
matrix metalloproteinase proteins. Of note, it was observed that 1-CP-U
significantly inhibited both the migration and invasion at a lower concentration,
as compared with the dose required to achieve significant inhibition of
apoptosis. These results indicated that 1-CP-U appeared to be a more effective
inhibitor of cell migration and invasion, rather than of apoptosis. In
conclusion, the present study was the first, to the best of our knowledge, to
demonstrate the function of 1-CP-U in tumor proliferation, apoptosis and invasion
with specific effects against cancer cells in vitro, suggesting 1-CP-U as a
potential novel anticancer agent.
PMID- 25118660
TI - Physical and sexual abuse and early-onset bipolar disorder in youths receiving
outpatient services: frequent, but not specific.
AB - The objective of this study was to determine if physical and sexual abuse showed
relationships to early-onset bipolar spectrum disorders (BPSD) consistent with
findings from adult retrospective data. Participants (N = 829, M = 10.9 years old
+/- 3.4 SD, 60% male, 69% African American, and 18% with BPSD), primarily from a
low socio-economic status, presented to an urban community mental health center
and a university research center. Physical abuse was reported in 21%, sexual
abuse in 20%, and both physical and sexual abuse in 11% of youths with BPSD. For
youths without BPSD, physical abuse was reported in 16%, sexual abuse in 15%, and
both physical and sexual abuse in 5% of youths. Among youth with BPSD, physical
abuse was significantly associated with a worse global family environment, more
severe depressive and manic symptoms, a greater number of sub-threshold
manic/hypomanic symptoms, a greater likelihood of suicidality, a greater
likelihood of being diagnosed with PTSD, and more self-reports of alcohol or drug
use. Among youth with BPSD, sexual abuse was significantly associated with a
worse global family environment, more severe manic symptoms, a greater number of
sub-threshold manic/hypomanic symptoms, greater mood swings, more frequent
episodes, more reports of past hospitalizations, and a greater number of current
and past comorbid Axis I diagnoses. These findings suggest that if physical
and/or sexual abuse is reported, clinicians should note that abuse appears to be
related to increased severity of symptoms, substance use, greater co-morbidity,
suicidality, and a worse family environment.
PMID- 25118661
TI - Effect of DTPP-mediated photodynamic therapy on cell morphology, viability, cell
cycle, and cytotoxicity in a murine lung adenocarcinoma cell line.
AB - Photodynamic therapy (PDT) involves the administration and activation of
photosensitizing reagents in cancer tissues to induce cytotoxicity. Here we
examined the effects of 5-5- (4-N, N-diacetoxylphenyl)-10,15,20-
tetraphenylporphyrin (DTPP) -mediated PDT on cell morphology, viability, cell
cycle, and cytotoxicity in a murine lung adenocarcinoma cell line. LA795 murine
lung adenocarcinoma cell line was used in the study, with cellular uptake of DTPP
being quantified by a UV-visible spectrophotometer. The subcellular localization
of DTPP was detected by confocal laser scanning microscopy, alteration of cell
morphology after PDT was observed by an inverted light microscope, and late-stage
apoptosis was examined by terminal dUTP nick end labeling (TUNEL) . The effects
of influencing factors on cytotoxicity of PDT in LA795 cells was investigated
with varying concentrations of DTPP, energy densities, power densities, and
antioxidants by 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
(MTT) assays. Effects of PDT on cell cycle and plasma membrane integrity were
studied by flow cytometry analysis. The uptake of DTPP by LA795 cells reached
maximum after incubation for 24 h. Confocal laser scanning microscopy showed that
DTPP was mainly in the mitochondrion, and slight localization was detected in the
lysosomes. Cellular inhibitory effects increased with increased irradiation dose
and DTPP concentration, while unactivated DTPP had low toxicity. Flow cytometry
analysis revealed that DTPP-PDT-treated cells showed S phase arrest. Cell
membrane damage initiation, repair, and irreversible damage were observed at 2,
4, and 5 h after DTPP-PDT , respectively. Together, our results demonstrated cell
apoptosis, compromised viability, and cell cycle S phase arrest of LA795 in
response to DTPP-PDT , while no effect on the lung cancer cells was observed with
irradiation or photosensitizer treatment alone.
PMID- 25118662
TI - Early detection of dental fluorosis using Raman spectroscopy and principal
component analysis.
AB - Raman spectroscopic technique has the potential to provide vibrational spectra of
minerals by analyzing scattered light caused by monochromatic laser excitation.
In this paper, recent applications of Raman spectroscopy in the study of dental
hard tissues are reported. Special attention is given to mineral components in
enamel and to calcium fluoride formed in/on enamel. The criteria used to classify
the dental hard samples were according to the Dean Index (DI), which consists
into healthy or control, mild, moderate, and severe, indicating the amount of
dental fluorosis observed on enamel. A total of 39 dental samples (9 control, 9
mild, 10 moderate, and 11 severe) were analyzed in the study. Dental samples were
positioned under an Olympus microscope, and around 10 points were chosen for
Raman measurement. All spectra were collected by a Horiba Jobin-Yvon LabRAM HR800
Raman Spectrometer with a laser of 830-nm and 17-mW power irradiation. Raw
spectra were processed by carrying out baseline correction, smoothing, and
normalization to remove noise, florescence, and shot noise and then analyzed
using principal component analysis (PCA). In the spectra of dental samples, we
observed the main bands as the broad band due to CO[Formula: see text] (240-300
cm (-1)), CaF 2 (322 cm (-1)), PO[Formula: see text] vibrations (437 and 450 cm (
1)), PO[Formula: see text] vibrations (582, 598, and 609 cm (-1)), PO[Formula:
see text] vibrations (960 cm (-1)), PO[Formula: see text] vibrations (1,045 cm (
1)), and CO[Formula: see text] vibration (1,073 cm (-1)). Nevertheless, the
intensity of the band at 960 cm (-1) associated to symmetric stretch of
phosphate, PO[Formula: see text], decreases as the amount of dental fluorosis
increases, suggesting that the intensity of this band could be used to
quantitatively measure the level of fluorosis on a dental sample. On the other
hand, PCA allowed to identify two large clusters discriminating between control,
and severe and moderate samples with high sensitivity and specificity. PCA was
able to discriminate mild from moderate samples with 100 % sensitivity and 89 %
specificity and mild from severe samples with 91 % sensitivity and 100 %
specificity. In addition, PCA was also able to discriminate between mild samples
and group formed by the moderate and severe samples with 95 % sensitivity and 89
% specificity. Finally, PCA allowed us to define the wavelength differences
between the spectral bands of the healthy teeth with sound enamel and those with
fluorosis by confirming that the main chemical differences among control and
severe fluorosis samples were associated to the vibrational modes of phosphate
(PO[Formula: see text], PO[Formula: see text], PO[Formula: see text], and
PO[Formula: see text] and carbonate (CO[Formula: see text]) ions. The preliminary
results suggest that Raman-PCA technique has the potential to be a noninvasive
real-time tool for the early detection and monitoring evolution of dental
fluorosis.
PMID- 25118663
TI - Are the mitochondrial respiratory complexes blocked by NO the targets for the
laser and LED therapy?
AB - Effects of laser (442 and 532 nm) and light-emitting diode (LED) (650 nm)
radiation on mitochondrial respiration and mitochondrial electron transport rate
(complexes II-III and IV) in the presence of nitric oxide (NO) were investigated.
It was found that nitric oxide (300 nM-10 MUM) suppresses mitochondrial
respiration. Laser irradiation of mitochondria (442 nm, 3 J cm(-2)) partly
restored mitochondrial respiration (approximately by 70 %). Irradiation with
green laser (532 nm) or red LED (650 nm) in the same dose had no reliable effect.
Evaluation of mitochondrial electron transport rate in complexes II-III and IV
and effects of nitric oxide demonstrated almost similar sensitivity of complex II
III and IV to NO, with approximately 50 % inhibition at NO concentration of 3
MUM. Subsequent laser or LED irradiation (3 J cm(-2)) showed partial recovery of
electron transport only in complex IV and only under irradiation with blue light
(442 nm). Our results support the hypothesis of the crucial role of cytochrome c
oxidase (complex IV) in photoreactivation of mitochondrial respiration suppressed
by NO.
PMID- 25118664
TI - Effect of different surface treatments on the microtensile bond strength of two
self-adhesive flowable composites.
AB - The aim of this study was to evaluate the effect of different surface treatments
on the microtensile bond strength (MUTBS) of two different self-adhesive flowable
composite materials (SACs) to dentin. Forty extracted human molars were
horizontally flattened to expose the dentin surfaces. The teeth were divided into
eight groups according to the surface treatments (acid etching, Er:YAG laser
quantum square pulse (QSP) mode, and Er:YAG laser medium-short pulse (MSP) mode
at 10 Hz, 1.2 W, 120 mJ, and control-SiC) and SAC type (Vertise Flow and Fusio
Liquid Dentin) (n = 5). Light cured 4-mm-high composite build-ups were made on
the dentin surfaces, and the specimens were sectioned into serial sticks (n =
15). Later, the specimens were attached to microtensile testing machine and
tensile force was applied at a crosshead speed of 1 mm/min until failure
occurred. The failure modes were evaluated using a stereomicroscope at *40
magnification, and one sample from each group was used for scanning electron
microscopy (SEM) evaluation. The data were analyzed with two-way ANOVA and
Tukey's HSD test (alpha = 0.05). In all surface treatment groups along with the
control groups, Vertise Flow showed better MUTBS than the Fusio Liquid Dentin
with the exception of the Er:YAG MSP mode surface treatment (p < 0.05). Etching
with phosphoric acid and the Er:YAG QSP mode surface treatment significantly
increased the MUTBS of Vertise Flow (p < 0.05). Etching with phosphoric acid,
Er:YAG QSP mode surface treatment, and Er:YAG MSP mode surface treatment
significantly increased the MUTBS of Fusio Liquid Dentin (p < 0.05). The MUTBS of
Vertise Flow was higher than the MUTBS of Fusio Liquid Dentin. The Er:YAG laser
irradiation increased the MUTBS of both self-adhesive flowable resin composites
in two pulse modes tested (MSP or QSP). However, the highest MUTBS was recorded
when Vertise Flow was applied with acid etching.
PMID- 25118665
TI - Electrocardiogram derived respiratory rate from QRS slopes and R-wave angle.
AB - A method for estimating respiratory rate from electrocardiogram (ECG) signals is
presented. It is based on QRS slopes and R-wave angle, which reflect respiration
induced beat morphology variations. The 12 standard leads, 3 leads from
vectorcardiogram (VCG), and 2 additional non-standard leads derived from VCG
loops were analyzed. The following series were studied as ECG derived respiration
(EDR) signals: slope between the peak of Q and R waves, slope between the peak of
R and S waves, and the R-wave angle. Information from several EDR signals was
combined in order to increase the robustness of estimation. Evaluation is
performed over two databases containing ECG and respiratory signals
simultaneously recorded during two clinical tests with different characteristics:
tilt test, representing abrupt cardiovascular changes, and stress test
representing a highly non-stationary and noisy environment. A combination of QRS
slopes and R-wave angle series derived from VCG leads obtained a respiratory rate
estimation relative error of 0.50 +/- 4.11% (measuring 99.84% of the time) for
tilt test and 0.52 +/- 8.99% (measuring 96.09% of the time) for stress test.
These results outperform those obtained by other reported methods, both in tilt
and stress testing.
PMID- 25118666
TI - Modeling of the acute effects of primary hypertension and hypotension on the
hemodynamics of intracranial aneurysms.
AB - Hemodynamics is a risk factor in intracranial aneurysms (IA). Hypertension and
pharmacologically induced hypotension are common in IA patients. This study
investigates how hypertension and hypotension may influence aneurysmal
hemodynamics. Images of 23 IAs at typical locations were used to build patient
specific Computational Fluid Dynamics models. The effects of hypotension and
hypertension were simulated through boundary conditions by modulating the
normotensive flow and pressure waveforms, in turn produced by a 1D systemic
vascular model. Aneurysm location and flow pattern types were used to categorize
the influence of hypotension and hypertension on relevant flow variables
(velocity, pressure and wall shear stress). Results indicate that, compared to
other locations, vertebrobasilar aneurysms (VBA) are more sensitive to flow
changes. In VBAs, space-averaged velocity at peak systole increased by 30% in
hypertension (16-21% in other locations). Flow in VBAs in hypotension decreased
by 20% (10-13% in other locations). Momentum-driven hemodynamic types were also
more affected by hypotension and hypertension, than shear-driven types. This
study shows how patient-specific modeling can be effectively used to identify
location-specific flow patterns in a clinically-relevant study, thus reinforcing
the role played by modeling technologies in furthering our understanding of
cardiovascular disease, and their potential in future healthcare.
PMID- 25118667
TI - Development of a 10-year-old full body geometric dataset for computational
modeling.
AB - The objective of this study was to create a computer-aided design (CAD) geometric
dataset of a 10-year-old (10 YO) child. The study includes two phases of efforts.
At Phase One, the 10 YO whole body CAD was developed from component computed
tomography and magnetic resonance imaging scans of 12 pediatric subjects.
Geometrical scaling methods were used to convert all component parts to the
average size for a 10 YO child, based on available anthropometric data. Then the
component surfaces were compiled and integrated into a complete body. The bony
structures and flesh were adjusted as symmetrical to minimize the bias from a
single subject while maintaining anthropometrical measurements. Internal organs
including the liver, spleen, and kidney were further verified by literature data.
At Phase Two, internal characteristics for the cervical spine disc, wrist, hand,
pelvis, femur, and tibia were verified with data measured from additional 94 10
YO children. The CAD dataset developed through these processes was mostly within
the corridor of one standard deviation (SD) of the mean. In conclusion, a
geometric dataset for an average size 10 YO child was created. The dataset serves
as a foundation to develop computational 10 YO whole body models for enhanced
pediatric injury prevention.
PMID- 25118668
TI - Accuracy and reproducibility of patient-specific hemodynamic models of stented
intracranial aneurysms: report on the Virtual Intracranial Stenting Challenge
2011.
AB - Validation studies are prerequisites for computational fluid dynamics (CFD)
simulations to be accepted as part of clinical decision-making. This paper
reports on the 2011 edition of the Virtual Intracranial Stenting Challenge. The
challenge aimed to assess the reproducibility with which research groups can
simulate the velocity field in an intracranial aneurysm, both untreated and
treated with five different configurations of high-porosity stents. Particle
imaging velocimetry (PIV) measurements were obtained to validate the untreated
velocity field. Six participants, totaling three CFD solvers, were provided with
surface meshes of the vascular geometry and the deployed stent geometries, and
flow rate boundary conditions for all inlets and outlets. As output, they were
invited to submit an abstract to the 8th International Interdisciplinary
Cerebrovascular Symposium 2011 (ICS'11), outlining their methods and giving their
interpretation of the performance of each stent configuration. After the
challenge, all CFD solutions were collected and analyzed. To quantitatively
analyze the data, we calculated the root-mean-square error (RMSE) over uniformly
distributed nodes on a plane slicing the main flow jet along its axis and
normalized it with the maximum velocity on the slice of the untreated case
(NRMSE). Good agreement was found between CFD and PIV with a NRMSE of 7.28%.
Excellent agreement was found between CFD solutions, both untreated and treated.
The maximum difference between any two groups (along a line perpendicular to the
main flow jet) was 4.0 mm/s, i.e. 4.1% of the maximum velocity of the untreated
case, and the average NRMSE was 0.47% (range 0.28-1.03%). In conclusion, given
geometry and flow rates, research groups can accurately simulate the velocity
field inside an intracranial aneurysm-as assessed by comparison with in vitro
measurements-and find excellent agreement on the hemodynamic effect of different
stent configurations.
PMID- 25118669
TI - Improvement of biodegradability, bioactivity, mechanical integrity and
cytocompatibility behavior of biodegradable mg based orthopedic implants using
nanostructured Bredigite (Ca7MgSi 4O 16) bioceramic coated via ASD/EPD technique.
AB - This research explored the influence of surface modification of AZ91 Mg alloy on
the biodegradation, bioactivity, mechanical integrity and cytocompatibility of
the alloy. For this purpose, a nanostructured bredigite (Ca7MgSi4O16) ceramic
coating was prepared on biodegradable AZ91 Mg alloy through anodic spark
deposition and electrophoretic deposition method. The phase composition and
surface morphology of the coated alloy were characterized by X-ray diffraction,
scanning electron microscope and transmission electron microscope. The properties
of samples were investigated by electrochemical measurements, immersion test,
compression examination and cell culturing. The results showed that the
degradation resistance, bioactivity, mechanical integrity and cytocompatibility
of biodegradable Mg alloy were improved by the anodic spark deposition and
electrophorretic deposition of the nanostructured bredigite coating. Therefore,
the nanostructured bredigite ceramic coating is identified as a good coating for
AZ91 Mg alloy for the purpose of making biodegradable metallic orthopedic
implants.
PMID- 25118670
TI - Permeability analysis of neuroactive drugs through a dynamic microfluidic in
vitro blood-brain barrier model.
AB - This paper presents the permeability analysis of neuroactive drugs and
correlation with in vivo brain/plasma ratios in a dynamic microfluidic blood
brain barrier (BBB) model. Permeability of seven neuroactive drugs (Ethosuximide,
Gabapentin, Sertraline, Sunitinib, Traxoprodil, Varenicline, PF-304014) and trans
endothelial electrical resistance (TEER) were quantified in both dynamic
(microfluidic) and static (transwell) BBB models, either with brain endothelial
cells (bEnd.3) in monoculture, or in co-culture with glial cells (C6). Dynamic
cultures were exposed to 15 dyn/cm(2) shear stress to mimic the in vivo
environment. Dynamic models resulted in significantly higher average TEER
(respective 5.9-fold and 8.9-fold increase for co-culture and monoculture models)
and lower drug permeabilities (average respective decrease of 0.050 and 0.052
log(cm/s) for co-culture and monoculture) than static models; and co-culture
models demonstrated higher average TEER (respective 90 and 25% increase for
static and dynamic models) and lower drug permeability (average respective
decrease of 0.063 and 0.061 log(cm/s) for static and dynamic models) than
monoculture models. Correlation of the resultant logP e values [ranging from
4.06 to -3.63 log(cm/s)] with in vivo brain/plasma ratios (ranging from 0.42 to
26.8) showed highly linear correlation (R (2) > 0.85) for all model conditions,
indicating the feasibility of the dynamic microfluidic BBB model for prediction
of BBB clearance of pharmaceuticals.
PMID- 25118672
TI - Parasitization of juvenile edible crabs (Cancer pagurus) by the dinoflagellate,
Hematodinium sp.: pathobiology, seasonality and its potential effects on
commercial fisheries.
AB - This study reports on the prevalence and severity of infections caused by the
parasitic dinoflagellate, Hematodinium in juvenile edible crabs (Cancer pagurus)
found in 2 intertidal survey sites (Mumbles Head and Oxwich Bay) in the Bristol
Channel, UK. Crabs were assessed for the presence and severity of Hematodinium
infections by the histological examination of infected tissues. Such infections
were found to exhibit a seasonal trend in the 2 study areas with high numbers of
animals (ca. 30%) infected in the spring to summer but with low severity.
Conversely, in November only ca. 10% of crabs were infected but these animals had
large numbers of parasites in their haemolymph and other tissues. At this time,
the carapace and underlying tissues of infected crabs had the chalky, pinkish
orange appearance that is characteristic of this disease. Hematodinium-infected
crabs ranged in size from 12 to 74 mm carapace width. Overall, it is concluded
that the high prevalence of infection of juvenile crabs in this area may have
implications for the sustainability of the edible crab fishery in the Bristol
Channel.
PMID- 25118673
TI - Recent patents on calcium channel blockers: emphasis on CNS diseases.
AB - INTRODUCTION: Altered homeostasis of cell calcium movement is a central stage in
multiple diseases of CNS. This explains the great therapeutic interest in
blockers for the various subtypes of voltage-activated calcium channels (VACCs)
expressed in neurons. Mitigation of Ca(2+) entry excess elicited by those
blockers may restore the altered synaptic transmission, synaptic plasticity and
gene expression to normal parameters, ending the enhanced neuronal vulnerability.
AREAS COVERED: This review summarize 23 patents on ligands for L-, N- or T-type
channels, claimed to have potential therapeutic interest in epilepsy, pain,
migraine and neurodegenerative diseases. EXPERT OPINION: Collections of compounds
are generally screened in cell lines expressing a given subtype of VACCs. IC50 to
block such channels are often, but not always, provided. In few instances,
compounds exhibiting the highest potency in in vitro experiments are also tested
in animal models of pain, behavior, epilepsy or Alzheimer's disease. Attempts to
develop selectivity for a given VACC subtype with non-peptidic organic ligands
have so far failed. Due to their wide tissue expression, such selectivity is
crucial for minimizing possible side effects. However, the few data reported by
patents does not allow prediction of selectivity of the new compounds in many
cases.
PMID- 25118671
TI - Characterization of abnormal wall shear stress using 4D flow MRI in human
bicuspid aortopathy.
AB - There exists considerable controversy surrounding the timing and extent of aortic
resection for patients with BAV disease. Since abnormal wall shear stress (WSS)
is potentially associated with tissue remodeling in BAV-related aortopathy, we
propose a methodology that creates patient-specific 'heat maps' of abnormal WSS,
based on 4D flow MRI. The heat maps were created by detecting outlier
measurements from a volumetric 3D map of ensemble-averaged WSS in healthy
controls. 4D flow MRI was performed in 13 BAV patients, referred for aortic
resection and 10 age-matched controls. Systolic WSS was calculated from this
data, and an ensemble-average and standard deviation (SD) WSS map of the controls
was created. Regions of the individual WSS maps of the BAV patients that showed a
higher WSS than the mean + 1.96SD of the ensemble-average control WSS map were
highlighted. Elevated WSS was found on the greater ascending aorta (35% +/- 15 of
the surface area), which correlated significantly with peak systolic velocity (R
(2) = 0.5, p = 0.01) and showed good agreement with the resected aortic regions.
This novel approach to characterize regional aortic WSS may allow clinicians to
gain unique insights regarding the heterogeneous expression of aortopathy and may
be leveraged to guide patient-specific resection strategies for aorta repair.
PMID- 25118675
TI - Common Mental Disorders at the Time of Deportation: A Survey at the Mexico-United
States Border.
AB - Deportations from the Unites States (US) to Mexico increased substantially during
the last decade. Considering deportation as a stressful event with potential
consequences on mental health, we aimed to (1) estimate the prevalence of common
mental disorders (CMD) among deported migrants; and (2) explore the association
between migratory experience, social support and psychological variables, and CMD
in this group. In repatriation points along the border, a probability sample of
deportees responded to the Self Reporting Questionnaire (SRQ). The prevalence of
CMD was 16.0% (95% CI 12.3, 20.6). There was a U-shaped association between time
in the US and SRQ score. Times returned to Mexico, having a spouse in the US,
number of persons in household, less social support, anxiety as a personality
trait, and avoidant coping style were directly associated with SRQ score. Public
health policies should address the need for mental health care among deported
migrants.
PMID- 25118677
TI - [Hereditary multiple exostoses].
AB - BACKGROUND: Hereditary multiple exostosis (HME) is a hereditary autosomal
dominant disease in which multiple exostoses occur. Typically, the exostoses are
primarily located at the metaphysis and migrate with continued growth towards the
diaphysis. Clinical problems are caused by local pain, impingement of muscle
tendons and neurovascular structures, malformation - especially in the forearm -
and malignant transformation - especially exostoses at the trunc and pelvic
girdle. METHODS: A causal therapy is currently not available. Mechanical
irritation is an indication for resection of the exostosis. Axial deviation of
the lower extremity is treated according to the same principles as primary
malalignments (temporary hemiepiphysiodesis/corrective osteotomy). RESULTS: The
indication for correction of axial deviation at the upper extremity depends on
age, extent as well as functional and cosmetic impairment. This should be
discussed with the patient in detail. The patient has to be informed about the
risk of malignant transformation after cessation of growth. Growing mass or new
occurrence of symptoms after end of growth are suspicious and require further
diagnostic examinations.
PMID- 25118676
TI - Two acidic, anticoagulant PLA2 isoenzymes purified from the venom of monocled
cobra Naja kaouthia exhibit different potency to inhibit thrombin and factor Xa
via phospholipids independent, non-enzymatic mechanism.
AB - BACKGROUND: The monocled cobra (Naja kaouthia) is responsible for snakebite
fatality in Indian subcontinent and in south-western China. Phospholipase A2
(PLA2; EC 3.1.1.4) is one of the toxic components of snake venom. The present
study explores the mechanism and rationale(s) for the differences in
anticoagulant potency of two acidic PLA2 isoenzymes, Nk-PLA2alpha (13463.91 Da)
and Nk-PLA2beta (13282.38 Da) purified from the venom of N. kaouthia. PRINCIPAL
FINDINGS: By LC-MS/MS analysis, these PLA2s showed highest similarity (23.5%
sequence coverage) with PLA2 III isolated from monocled cobra venom. The
catalytic activity of Nk-PLA2beta exceeds that of Nk-PLA2alpha. Heparin
differentially regulated the catalytic and anticoagulant activities of these Nk
PLA2 isoenzymes. The anticoagulant potency of Nk-PLA2alpha was comparable to
commercial anticoagulants warfarin, and heparin/antithrombin-III albeit Nk
PLA2beta demonstrated highest anticoagulant activity. The anticoagulant action of
these PLA2s was partially contributed by a small but specific hydrolysis of
plasma phospholipids. The strong anticoagulant effect of Nk-PLA2alpha and Nk
PLA2beta was achieved via preferential, non-enzymatic inhibition of FXa (Ki = 43
nM) and thrombin (Ki = 8.3 nM), respectively. Kinetics study suggests that the Nk
PLA2 isoenzymes inhibit their "pharmacological target(s)" by uncompetitive
mechanism without the requirement of phospholipids/Ca(2+). The anticoagulant
potency of Nk-PLA2beta which is higher than that of Nk-PLA2alpha is corroborated
by its superior catalytic activity, its higher capacity for binding to
phosphatidylcholine, and its greater strength of thrombin inhibition. These PLA2
isoenzymes thus have evolved to affect haemostasis by different mechanisms. The
Nk-PLA2beta partially inhibited the thrombin-induced aggregation of mammalian
platelets suggesting its therapeutic application in the prevention of unwanted
clot formation. CONCLUSION/SIGNIFICANCE: In order to develop peptide-based
superior anticoagulant therapeutics, future application of Nk-PLA2alpha and Nk
PLA2beta for the treatment and/or prevention of cardiovascular disorders are
proposed.
PMID- 25118679
TI - [Spondylosclerosis hemispherica: a rare radiological syndrome of the spine].
AB - BACKGROUND: Spondylosclerosis hemispherica is a rare syndrome of the spine and
was described first by Dihlmann. The typical radiographic appearance is a
hemispherical sclerosis of the vertebral body, which is accompanied by pain in
the affected region. Usually it appears at the lower lumbar spine. The etiology
varies and includes degenerative disk diseases, scoliosis, bacterial infections,
ankylosing spondylitis, osteoid osteoma, and malignant diseases.The radiological
findings of 2 patients with spondylosclerosis hemispherica are presented and the
current literature discussed. MATERIAL AND METHODS: Two women (33 and 60 years
old) with spondylosclerosis hemispherica of the lower spine suffered from low
back pain and fulfilled all criteria of Dihlmann's description. Malignant disease
was excluded in both cases with a broad diagnostic workup (lab values, x-ray, CT
scan, MRI) and in one case a biopsy from the affected vertebra was taken.
RESULTS: In both cases all radiological findings demonstrated the typical changes
of spondylosclerosis hemispherica with sclerosis of the vertebra body and
erosions at the upper and inferior end plates. Malignant disease was excluded in
one case with a biopsy and in the other case with noninvasive diagnostic
procedures. Both patients were treated nonsurgically. During clinical follow-up,
the patients were in a good condition with decreasing regional low back pain and
no ongoing radiological changes in the affected vertebral bodies. CONCLUSION:
Spondylosclerosis hemispherica is a syndrome with a typical radiographic
appearance. The etiology of spondylosclerosis hemispherica is manifold; however,
malignancy must be excluded. In most cases, noninvasive diagnostics are
sufficient to rule out malignant growth even in cases with concomitant
degenerative changes of the affected segment. Thus, there is no need for a biopsy
except in cases with ambiguous results. Subsequently, close clinical and
radiological follow-up of the patients with spondylosclerosis hemispherica is
necessary.
PMID- 25118678
TI - [Surgical treatment of scapholunate ligament injuries: clinical and radiological
results].
AB - BACKGROUND: The purpose of this work was to retrospectively evaluate clinical and
radiological results after surgical treatment for scapholunate ligament ruptures.
MATERIALS AND METHODS: Measurements of range of motion, strength, and angles, as
well as postoperative score assessments were performed in 32 patients. RESULTS:
The average mobility in the operated wrist was 52 degrees for flexion, extension
57 degrees , radial 24 degrees , ulnar deviation 31 degrees and forearm rotation
outward 88 degrees and inward 89 degrees . The recovery of force was 89%
compared with the healthy hand. It showed an average skapholunar angle of 63
degrees , a radioulnar angle of 22 degrees and an average carpal height
according to Nattrass of 1.49. Our patients rated the operation result with a
median DASH score of 11 points (range 0-70.8 points). The median objective Mayo
Wrist Score was 80 points (range 45-100 points). CONCLUSION: Surgical treatment
of scapholunate ligament rupture, especially against the background of carpal
collapse, is a very satisfactory method with very good results in the objective
function and strength, and a high level of patient satisfaction.
PMID- 25118680
TI - [Cement-free and cemented Excia hip shaft prosthesis: comparison of intermediate
term results].
AB - AIM OF THE STUDY: For fixation of total hip prostheses, cemented and cement-free
techniques are available. Normally, anchoring techniques and the definitive
endoprosthesis model are determined preoperatively based on the available
information, such as the quality of bone. Some newer endoprosthesis models
utilize the same instruments for both implantation techniques. In this way it is
possible to decide on the final anchoring technique intraoperatively. Because
such a combined endoprosthesis system has been used in our clinic for 10 years,
we were interested in the clinical results at the intermediate stage. MATERIAL
AND METHODS: In a prospective, non-randomized study 105 pairs from a continuing
series were formed from 105 cases treated with cement-free prostheses and the
latest cemented shaft implants from the same year. In this way a total of 210 hip
shaft endoprostheses from the years 2002 to 2006 were included in the study.
After an average time period of 6.3 years (range 4.5-8.2 years) the patients were
recalled for a follow-up examination. The clinical results, early and late
complications were analyzed. The immediately postoperative X-ray images and those
from the follow-up examination were evaluated by an independent external expert
with respect to primary positioning, migration and any signs of loosening.
RESULTS: At the follow-up examination at an average of 6.3 years the quota was
73%. The indications for cement-free/cemented total hip endoprosthesis were:
primary arthritis 87%/98%, secondary arthritis 10%/2% and others 3%/0%. At the
time of the last follow-up examination 4 and 14 patients, respectively, had died.
The visual analog scale (VAS) for pain was given as 0.72/0.78. The Harris hip
score improved from 54/48 to 93/90 points. The implant-related survival rate was
99.5%. Due to a periprosthetic fracture one of the cemented shafts had to be
removed. Luxation occurred in 3/2 cases, respectively, of which 4 could be
conservatively treated. In one cement-free case a head elongation and a change to
an inlay with an anti-luxation shoulder was necessary. A fracture of the
trochanter major was conservatively treated and an intraoperative shaft fissure
was stabilized with wire cerclage and titan banding. The radiological evaluation
showed no implant loosening or statistically significant differences in the shaft
positioning. DISCUSSION: Short and intermediate clinical and radiological results
showed no differences in patients of similar average age in the sixth decade of
life. The significant improvements in the Harris hip score and the range of
movement could be confirmed in the intermediate term and are comparable to other
current implants. It can be concluded that an intraoperative decision on the
fixation technique based on the macroscopically visible bone quality supports the
reliably good results of both methods.
PMID- 25118681
TI - [Partial knee replacement].
PMID- 25118683
TI - Answer to the letter to the editor of L. Uhrenholt et al. concerning "do X-ray
occult fractures play a role in chronic pain following a whiplash injury?" by
Hertzum-Larsen R, Petersen H, Kasch H, Bendix T, Eur Spine J, 2014; DOI
10.1007/s00586-014-3362-3.
PMID- 25118689
TI - Erysipeloid Hodgkin lymphoma.
PMID- 25118684
TI - Epithelioid hemangioendothelioma of the spine: results at seven years of average
follow-up in a series of 10 cases surgically treated and a review of literature.
AB - PURPOSE: To review a series of ten cases with epithelioid hemangioendothelioma of
the spine, that have undergone surgery to describe clinical presentation, results
and complications associated with surgical treatment; a review of literature
reporting the main characteristics of the cases already published has been
reported. METHODS: A review of patients affected by epithelioid
hemangioendothelioma surgically treated by the senior author from 1995 to 2012
was carried out. Ten cases were identified and clinical and radiological
characteristics, therapy, complications and survival were valued. RESULTS: Wide
margin was achieved in two out of ten cases, marginal margin in seven and
intralesional margin in one case. Average intraoperative blood loss was about
2,800 ml. Reported complications were one case of cord injury, one of dural tear,
two cases of massive blood loss, a case of reconstruction failure, a wound
dehiscence with deep infection, a pneumonia episode and a deep vein thrombosis
with pulmonary embolism. Average follow-up was 84.4 months. Two local
recurrences, after 32 and 37 months and two deaths for metastasis, after 14 and
36 months, were reported. Although several chemotherapy protocols are available
for the treatment of EH of soft tissue, they are not relevant for the bone.
CONCLUSIONS: Wide surgery is probably associated with a better prognosis. Indeed
most deaths and local recurrences reported in literature happened after
intralesional surgery or chemotherapy/RT alone. The presenting study suggests
that the best approach to achieve long-term local control and a major survival
could be wide surgery, nevertheless more cases series are necessary to verify
survival rate.
PMID- 25118685
TI - Comparison between walking test and treadmill test for intermittent claudication
associated with lumbar spinal canal stenosis.
AB - PURPOSE: To clarify the priorities of the walking test and the treadmill test for
intermittent claudication of lumbar canal stenosis. METHODS: The study population
comprised 45 subjects, with a mean age of 72.6 years. An investigator walked with
the subjects during the walking test or watched the subjects walking on the
treadmill machine in the treadmill test. RESULTS: The pain scales became
significantly worse after the walking test. Ten patients who were diagnosed as
root symptom type or cauda equine symptoms were subsequently diagnosed as mixed
type by the walking test. The numbers of patients who experienced muscle weakness
that was not revealed at rest were eight with the walking test and seven with the
treadmill test. The numbers of patients who experienced sensory disturbance that
was not observed at rest were seven with the walking test and two with the
treadmill test. CONCLUSIONS: The walking test detected significantly more
symptoms that were not detected at rest than the treadmill test.
PMID- 25118690
TI - Site-directed mutagenesis of IRX9, IRX9L and IRX14 proteins involved in xylan
biosynthesis: glycosyltransferase activity is not required for IRX9 function in
Arabidopsis.
AB - Xylans constitute the main non-cellulosic polysaccharide in the secondary cell
walls of plants. Several genes predicted to encode glycosyltransferases are
required for the synthesis of the xylan backbone even though it is a homopolymer
consisting entirely of beta-1,4-linked xylose residues. The putative
glycosyltransferases IRX9, IRX14, and IRX10 (or the paralogs IRX9L, IRX14L, and
IRX10L) are required for xylan backbone synthesis in Arabidopsis. To investigate
the function of IRX9, IRX9L, and IRX14, we identified amino acid residues known
to be essential for catalytic function in homologous mammalian proteins and
generated modified cDNA clones encoding proteins where these residues would be
mutated. The mutated gene constructs were used to transform wild-type Arabidopsis
plants and the irx9 and irx14 mutants, which are deficient in xylan synthesis.
The ability of the mutated proteins to complement the mutants was investigated by
measuring growth, determining cell wall composition, and microscopic analysis of
stem cross-sections of the transgenic plants. The six different mutated versions
of IRX9 and IRX9-L were all able to complement the irx9 mutant phenotype,
indicating that residues known to be essential for glycosyltransferases function
in homologous proteins are not essential for the biological function of
IRX9/IRX9L. Two out of three mutated IRX14 complemented the irx14 mutant,
including a mutant in the predicted catalytic amino acid. A IRX14 protein mutated
in the substrate-binding DxD motif did not complement the irx14 mutant. Thus,
substrate binding is important for IRX14 function but catalytic activity may not
be essential for the function of the protein. The data indicate that IRX9/IRX9L
have an essential structural function, most likely by interacting with the
IRX10/IRX10L proteins, but do not have an essential catalytic function. Most
likely IRX14 also has primarily a structural role, but it cannot be excluded that
the protein has an important enzymatic activity.
PMID- 25118691
TI - An appraisal of female sex work in Nigeria--implications for designing and
scaling up HIV prevention programmes.
AB - BACKGROUND: The HIV epidemic in Nigeria is complex with diverse factors driving
the epidemic. Accordingly, Nigeria's National Agency for the Control of AIDS is
coordinating a large-scale initiative to conduct HIV epidemic appraisals across
all states. These appraisals will help to better characterize the drivers of the
epidemic and ensure that the HIV prevention programmes match the local epidemic
context, with resources allocated to interventions that have the greatest impact
locally. Currently, the mapping and size estimation of Female Sex Workers (FSWs)-
a major component of the appraisal has been completed in seven states. These
states are using the data generated to plan, prioritize and scale-up sub-national
HIV prevention programmes. METHODOLOGY: It involved a two-level process of
identifying and validating locations where FSWs solicit and/or meet clients
("hotspots"). In the first level, secondary key informants were interviewed to
collect information about the geographic location and description of the
hotspots. For the second level, FSWs were interviewed at each hotspot and
information on population size estimates, typologies and operational dynamics of
the FSWs were collected. RESULTS: Across the seven states, a total of 17,266
secondary key informants and 5,732 FSWs were interviewed. 10,233 hotspots were
identified with an estimated 126,489 FSWs ranging from 5,920 in Anambra to 46,691
in Lagos. The most common hotspots were bars/nightclubs (30%), hotels/lodges
(29.6%), streets (16.6%), and brothels (14.6%). Furthermore, the population
density of FSWs (per thousand adult men) across the states ranged from 2 in
Anambra to 17 in the Federal Capital Territory. CONCLUSION: FSW populations in
Nigeria are large and diverse, with substantial differences between and within
states. Improved understanding of the location, population size, density,
organizational typologies and clients of sex work has informed and is central to
Nigeria's planning process for scaling up focused HIV prevention programmes.
PMID- 25118692
TI - Pregnancy-related systemic lupus erythematosus: clinical features, outcome and
risk factors of disease flares--a case control study.
AB - OBJECTIVE: To investigate the clinical features, outcome, and risk factors of
disease flares in patients with pregnancy-related lupus (PRL). METHODS: Medical
charts of 155 consecutive PRL inpatients were systematically reviewed, including
demographic data, clinical features, laboratory findings, treatment,
complications, and outcome. RESULTS: PRL cases were divided into active (a-PRL)
(n = 82, 53.0%) and stable lupus (s-PRL) (n = 73, 47.0%). Compared with
nonpregnant active female systemic lupus erythematosus (SLE) patients, a-PRL
including new-onset lupus (n-PRL) and flare lupus (f-PRL) (n = 41 respectively),
had a higher incidence of renal and hematological involvement but less
mucocutaneous and musculoskeletal involvement (p<0.05). The incidence of
preeclampsia/eclampsia, fetal loss, and preterm birth were significantly higher
in a-PRL than in s-PRL (p<0.05). Despite receiving a more vigorous glucocorticoid
treatment, a-PRL mothers had a poorer prognosis (p<0.001). Five (6.1%) of them
died and 13 (15.9%) developed severe irreversible organ failure, whereas none of
these events was observed in the s-PRL group. Multivariate logistic analysis
indicated that a history of lupus flares and serological activity
(hypocomplementemia and/or anti-dsDNA positivity) at the time of conception were
associated with lupus flares in PRL mothers. CONCLUSIONS: SLE patients with a
flare history and serological activity at the time of conception were at an
increased risk of disease flares during pregnancy and puerperium. a-PRL patients
were more prone to renal and hematological involvement, pregnancy complications,
and a poorer prognosis despite more vigorous glucocorticoid treatment.
PMID- 25118694
TI - Statin therapy is associated with improved survival in patients with non-serous
papillary epithelial ovarian cancer: a retrospective cohort analysis.
AB - AIM: To determine whether statin use is associated with improved epithelial
ovarian cancer (OvCa) survival. METHODS: This is a single-institution
retrospective cohort review of patients treated for OvCa between 1992 and 2013.
Inclusion criteria were International Federation of Gynecology and Obstetrics
(FIGO) stage I-IV OvCa. The primary exposures analyzed were hyperlipidemia and
statin use. The primary outcomes were progression-free survival (PFS) and disease
specific survival (DSS). RESULTS: 442 patients met inclusion criteria. The cohort
was divided into three groups: patients with hyperlipidemia who used statins (n =
68), patients with hyperlipidemia who did not use statins (n = 28), and patients
without hyperlipidemia (n = 346). OvCa outcomes were evaluated. When we analyzed
the entire cohort, we found no significant differences in PFS or DSS among the
groups. The median PFS for hyperlipidemics using statins, hyperlipidemics not
using statins, and non-hyperlipidemics was 21.7, 13.6, and 14.7 months,
respectively (p = 0.69). Median DSS for hyperlipidemics using statins,
hyperlipidemics not using statins, and non-hyperlipidemics was 44.2, 75.7, and
41.5 months, respectively (p = 0.43). These findings did not change after
controlling for confounders. However, a secondary analysis revealed that, among
patients with non-serous-papillary subtypes of OvCa, statin use was associated
with a decrease in hazards of both disease recurrence (adjusted HR = 0.23, p =
0.02) and disease-specific death (adjusted HR = 0.23, p = 0.04). To augment the
findings in the retrospective cohort, the histology-specific effects of statins
were also evaluated in vitro using proliferation assays. Here, statin treatment
of cell lines resulted in a variable level of cytotoxicity. CONCLUSION: Statin
use among patients with non-serous-papillary OvCa was associated with improvement
in both PFS and DSS.
PMID- 25118695
TI - Involvement of the carboxyl-terminal region of the yeast peroxisomal half ABC
transporter Pxa2p in its interaction with Pxa1p and in transporter function.
AB - BACKGROUND: The peroxisome is a single membrane-bound organelle in eukaryotic
cells involved in lipid metabolism, including beta-oxidation of fatty acids. The
human genetic disorder X-linked adrenoleukodystrophy (X-ALD) is caused by
mutations in the ABCD1 gene (encoding ALDP, a peroxisomal half ATP-binding
cassette [ABC] transporter). This disease is characterized by defective
peroxisomal beta-oxidation and a large accumulation of very long-chain fatty
acids in brain white matter, adrenal cortex, and testis. ALDP forms a homodimer
proposed to be the functional transporter, whereas the peroxisomal transporter in
yeast is a heterodimer comprising two half ABC transporters, Pxa1p and Pxa2p,
both orthologs of human ALDP. While the carboxyl-terminal domain of ALDP is
engaged in dimerization, it remains unknown whether the same region is involved
in the interaction between Pxa1p and Pxa2p. METHODS/PRINCIPAL FINDINGS: Using a
yeast two-hybrid assay, we found that the carboxyl-terminal region (CT) of Pxa2p,
but not of Pxa1p, is required for their interaction. Further analysis indicated
that the central part of the CT (designated CT2) of Pxa2p was indispensable for
its interaction with the carboxyl terminally truncated Pxa1_NBD. An interaction
between the CT of Pxa2p and Pxa1_NBD was not detected, but could be identified in
the presence of Pxa2_NBD-CT1. A single mutation of two conserved residues
(aligned with X-ALD-associated mutations at the same positions in ALDP) in the
CT2 of the Pxa2_NBD-CT protein impaired its interaction with Pxa1_NBD or Pxa1_NBD
CT, resulting in a mutant protein that exhibited a proteinase K digestion profile
different from that of the wild-type protein. Functional analysis of these mutant
proteins on oleate plates indicated that they were defective in transporter
function. CONCLUSIONS/SIGNIFICANCE: The CT of Pxa2p is involved in its
interaction with Pxa1p and in transporter function. This concept may be applied
to human ALDP studies, helping to establish the pathological mechanism for CT
related X-ALD disease.
PMID- 25118696
TI - Analysis of the Citrullus colocynthis transcriptome during water deficit stress.
AB - Citrullus colocynthis is a very drought tolerant species, closely related to
watermelon (C. lanatus var. lanatus), an economically important cucurbit crop.
Drought is a threat to plant growth and development, and the discovery of drought
inducible genes with various functions is of great importance. We used high
throughput mRNA Illumina sequencing technology and bioinformatic strategies to
analyze the C. colocynthis leaf transcriptome under drought treatment. Leaf
samples at four different time points (0, 24, 36, or 48 hours of withholding
water) were used for RNA extraction and Illumina sequencing. qRT-PCR of several
drought responsive genes was performed to confirm the accuracy of RNA sequencing.
Leaf transcriptome analysis provided the first glimpse of the drought responsive
transcriptome of this unique cucurbit species. A total of 5038 full-length cDNAs
were detected, with 2545 genes showing significant changes during drought stress.
Principle component analysis indicated that drought was the major contributing
factor regulating transcriptome changes. Up regulation of many transcription
factors, stress signaling factors, detoxification genes, and genes involved in
phytohormone signaling and citrulline metabolism occurred under the water deficit
conditions. The C. colocynthis transcriptome data highlight the activation of a
large set of drought related genes in this species, thus providing a valuable
resource for future functional analysis of candidate genes in defense of drought
stress.
PMID- 25118697
TI - The effect of lentivirus-mediated PSPN genetic engineering bone marrow
mesenchymal stem cells on Parkinson's disease rat model.
AB - Persephin (PSPN) is one of the neurotrophic factors of the glial cell line
derived neurotrophic factor (GDNF) family ligands (GFLs) which have been found to
promote the survival of specific populations of neurons. The aim of this study
was to assess the potential therapeutic function of gene-modified mesenchymal
stem cells (MSCs)-Lv-PSPN-MSCs in 6-OHDA-induced Parkinson's disease (PD) rats
models. Here, we worked on the isolation, purification, identification and
amplification of MSCs in vitro. The expression analysis revealed that several of
the neural marker proteins like nestin, GFAP and S100 were expressed by rat MSCs.
MES23.5 cells co-cultured with Lv-PSPN-MSCs showed less 6-OHDA induced cell death
than control cells in vitro. When Lv-PSPN-MSCs were injected into the striatum of
PD rats, we observed the survival rate, migration, differentiation and the
behavior change of PD rats. We found that Lv-PSPN-MSCs showed higher survival
rate in rat brain compared with Lv-null-MSCs. Rotational behavior showed that
rats receiving Lv-PSPN-MSCs showed the most significant improvement compared with
those in other groups. HPLC results showed the content of DA in striatum of rats
which received Lv-PSPN-MSCs was highest compared with those in other groups. In
conclusion, our results suggest that transplantation of Lv-PSPN-MSCs can lead to
remarkable therapeutic effects in PD rats.
PMID- 25118699
TI - Atopic Dermatitis Burden Scale for Adults: Development and Validation of a New
Assessment Tool.
AB - Atopic dermatitis (AD) occurs in approximately 2-3% of adults. The aim of this
study was to develop and validate the self-administered Atopic Dermatitis Burden
Scale for Adults (ABS-A). Patients were enrolled consecutively from those
attending the Station Thermale Avene for a diagnosis of AD. ABS-A was developed
using standard methodology, and consisted of 3 phases: exploratory, development,
and validation. Internal consistency (Cronbach's alpha), concurrent validity
(Spearman's correlation between ABS-A, SF-12 and Dermatology Life Quality Index
[DLQI)]), and discriminant validity, were analysed. A total of 128 adults (68.8%
females) completed the ABS-A, consisting of 18 items grouped into 4 domains. ABS
A showed good internal coherence (Cronbach's alpha, 0.89) and was correlated with
both SF-12 components [r = -0.36, p < 0.0001 (Physical); r = -0.52, p < 0.0001
(Mental)] and DLQI (r = 0.78; p < 0.0001). The ABS-A score varied significantly
according to AD severity. To our knowledge, ABS-A is the first specific tool for
assessing AD burden in adult patients.
PMID- 25118698
TI - Rapid detection of Mycobacterium tuberculosis by recombinase polymerase
amplification.
AB - Improved access to effective tests for diagnosing tuberculosis (TB) has been
designated a public health priority by the World Health Organisation. In high
burden TB countries nucleic acid based TB tests have been restricted to
centralised laboratories and specialised research settings. Requirements such as
a constant electrical supply, air conditioning and skilled, computer literate
operators prevent implementation of such tests in many settings. Isothermal DNA
amplification technologies permit the use of simpler, less energy intensive
detection platforms more suited to low resource settings that allow the accurate
diagnosis of a disease within a short timeframe. Recombinase Polymerase
Amplification (RPA) is a rapid, low temperature isothermal DNA amplification
reaction. We report here RPA-based detection of Mycobacterium tuberculosis
complex (MTC) DNA in <20 minutes at 39 degrees C. Assays for two MTC specific
targets were investigated, IS6110 and IS1081. When testing purified MTC genomic
DNA, limits of detection of 6.25 fg (IS6110) and 20 fg (IS1081)were consistently
achieved. When testing a convenience sample of pulmonary specimens from suspected
TB patients, RPA demonstrated superior accuracy to indirect fluorescence
microscopy. Compared to culture, sensitivities for the IS1081 RPA and microscopy
were 91.4% (95%CI: 85, 97.9) and 86.1% (95%CI: 78.1, 94.1) respectively (n = 71).
Specificities were 100% and 88.6% (95% CI: 80.8, 96.1) respectively. For the
IS6110 RPA and microscopy sensitivities of 87.5% (95%CI: 81.7, 93.2) and 70.8%
(95%CI: 62.9, 78.7) were obtained (n = 90). Specificities were 95.4 (95% CI:
92.3,98.1) and 88% (95% CI: 83.6, 92.4) respectively. The superior specificity of
RPA for detecting tuberculosis was due to the reduced ability of fluorescence
microscopy to distinguish Mtb complex from other acid fast bacteria. The rapid
nature of the RPA assay and its low energy requirement compared to other
amplification technologies suggest RPA-based TB assays could be of use for
integration into a point-of-care test for use in resource constrained settings.
PMID- 25118700
TI - Modulation of short-latency afferent inhibition depends on digit and task
relevance.
AB - Short-latency afferent inhibition (SAI) occurs when a single transcranial
magnetic stimulation (TMS) pulse delivered over the primary motor cortex is
preceded by peripheral electrical nerve stimulation at a short inter-stimulus
interval (~ 20-28 ms). SAI has been extensively examined at rest, but few studies
have examined how this circuit functions in the context of performing a motor
task and if this circuit may contribute to surround inhibition. The present study
investigated SAI in a muscle involved versus uninvolved in a motor task and
specifically during three pre-movement phases; two movement preparation phases
between a "warning" and "go" cue and one movement initiation phase between a "go"
cue and EMG onset. SAI was tested in the first dorsal interosseous (FDI) and
abductor digiti minimi (ADM) muscles in twelve individuals. In a second
experiment, the origin of SAI modulation was investigated by measuring H-reflex
amplitudes from FDI and ADM during the motor task. The data indicate that changes
in SAI occurred predominantly in the movement initiation phase during which SAI
modulation depended on the specific digit involved. Specifically, the greatest
reduction in SAI occurred when FDI was involved in the task. In contrast, these
effects were not present in ADM. Changes in SAI were primarily mediated via
supraspinal mechanisms during movement preparation, while both supraspinal and
spinal mechanisms contributed to SAI reduction during movement initiation.
PMID- 25118702
TI - Optimizing the discovery and clinical translation of nanoparticles: could
microfluidics hold the key?
PMID- 25118703
TI - Recent progress in multidrug delivery to cancer cells by liposomes.
PMID- 25118704
TI - Formulating the magic bullet: barriers to clinical translation of nanoparticle
cancer gene therapy.
PMID- 25118701
TI - Impact of early life adversity on reward processing in young adults: EEG-fMRI
results from a prospective study over 25 years.
AB - Several lines of evidence have implicated the mesolimbic dopamine reward pathway
in altered brain function resulting from exposure to early adversity. The present
study examined the impact of early life adversity on different stages of neuronal
reward processing later in life and their association with a related behavioral
phenotype, i.e. attention deficit/hyperactivity disorder (ADHD). 162 healthy
young adults (mean age = 24.4 years; 58% female) from an epidemiological cohort
study followed since birth participated in a simultaneous EEG-fMRI study using a
monetary incentive delay task. Early life adversity according to an early family
adversity index (EFA) and lifetime ADHD symptoms were assessed using standardized
parent interviews conducted at the offspring's age of 3 months and between 2 and
15 years, respectively. fMRI region-of-interest analysis revealed a significant
effect of EFA during reward anticipation in reward-related areas (i.e. ventral
striatum, putamen, thalamus), indicating decreased activation when EFA increased.
EEG analysis demonstrated a similar effect for the contingent negative variation
(CNV), with the CNV decreasing with the level of EFA. In contrast, during reward
delivery, activation of the bilateral insula, right pallidum and bilateral
putamen increased with EFA. There was a significant association of lifetime ADHD
symptoms with lower activation in the left ventral striatum during reward
anticipation and higher activation in the right insula during reward delivery.
The present findings indicate a differential long-term impact of early life
adversity on reward processing, implicating hyporesponsiveness during reward
anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar
activation pattern related to lifetime ADHD suggests that the impact of early
life stress on ADHD may possibly be mediated by a dysfunctional reward pathway.
PMID- 25118707
TI - A preliminary study on the quality and safety of milk in donkeys positive for
Toxoplasma gondii.
AB - Toxoplasmosis is one of the five parasitic diseases considered as a priority for
public health action. The consumption of raw milk products represents a possible
risk, in particular for certain categories of people. The aim of this study was
to evaluate the possible effects of Toxoplasma gondii on milk yield and quality
in sero-positive animals with parasitemia. Eighteen healthy lactating Amiata
jennies, between 90 and 180 days were included in the study. Four donkeys scored
positive for immunofluorescent antibody test (IFAT), and each IFAT positive
donkey presented parasitic DNA both in the blood and milk. No significant
differences were found between milk yield in PCR-positive donkeys compared with
the negative cases, however the former tended to have a greater production. Milk
quality in the positive donkeys showed a significantly lower percentage of casein
(0.72% v. 0.81%) and ash (0.32% v. 0.37%). Positive cases had a highly
significant larger average diameter of globules (2.35 um) and fewer globules/ml
(2.39 * 10(8)). Somatic cell and bacterial counts were normal and in agreement
with the literature. Toxoplasma gondii did not seem to present clinical forms in
lactating jennies. Further in vivo studies are needed to further assess the risk
of T. gondii transmission through donkey milk, together with the impact of
different stages of infection on milk quality.
PMID- 25118708
TI - Association of a polymorphism in the BIRC6 gene with pseudoexfoliative glaucoma.
AB - Recently an association was observed between alleles in genes of the unfolded
protein response pathway and primary open angle glaucoma (POAG). The goal of the
current study is to investigate the role of these two genes, protein disulphide
isomerase A member 5 (PDIA5) and baculoviral IAP repeat containing 6 (BIRC6), in
different forms of glaucoma. 278 patients with POAG, 132 patients with primary
angle closure glaucoma (PACG) and 135 patients with pseudoexfoliative glaucoma
(PEXG) were genotyped for single nucleotide polymorphisms (SNPs) rs11720822 in
PDIA5 and 471 POAG, 184 PACG and 218 PEXG patients were genotyped for rs2754511
in BIRC6. Genotyping was done by allelic discrimination PCR, and genotype and
allele frequencies were calculated. Logistic regression analyses were performed
using R software to determine the association of these SNPs with glaucoma. The
allele and genotype frequencies of rs11720822 in PDIA5 were not associated with
POAG, PACG or PEXG. The TT genotype of rs2754511 in BIRC6 was found to be
protective for PEXG (p = 0.05, OR 0.42 [0.22-0.81]) in the Pakistani population,
but not for POAG or PACG. This study did not confirm a previously reported
association of risk alleles in PDIA5 and BIRC6 with POAG, but did demonstrate a
protective role of the T allele of rs2754511 in the BIRC6 gene in PEXG. This
supports a role for the unfolded protein response pathway and regulation of
apoptotic cell death in the pathogenesis of PEXG.
PMID- 25118710
TI - Fullerene C60 functionalized gamma-Fe2O3 magnetic nanoparticle: Synthesis,
characterization, and biomedical applications.
AB - Hybrid magnetic nanoparticles composed from C60 fullerene and gamma-Fe2O3 were
synthesized by hydrothermal method. XRD, FT-IR, VSM, SEM, and HR-TEM were
employed for characterizations. The magnetic saturation value of C60-gamma-Fe2O3
magnetic nanoparticles was 66.5 emu g(-1). Concentration of Fe in nanoparticles
as determined by ICP-OES was 40.7% Fe. Particle size of C60-gamma-Fe2O3 magnetic
nanoparticles was smaller than 10 nm. Maximum adsorption capacity of C60-gamma
Fe2O3 for flurbiprofen, a non-steroidal anti-inflammatory drug, was calculated
from Langmuir isotherm as 142.9 mg g(-1).
PMID- 25118711
TI - Multimode laser cooling and ultra-high sensitivity force sensing with nanowires.
AB - Photo-induced forces can be used to manipulate and cool the mechanical motion of
oscillators. When the oscillator is used as a force sensor, such as in atomic
force microscopy, active feedback is an enticing route to enhance measurement
performance. Here we show broadband multimode cooling of -23 dB down to a
temperature of 8 +/- 1 K in the stationary regime. Through the use of periodic
quiescence feedback cooling, we show improved signal-to-noise ratios for the
measurement of transient signals. We compare the performance of real feedback to
numerical post processing of data and show that both methods produce similar
improvements to the signal-to-noise ratio of force measurements. We achieved a
room temperature force measurement sensitivity of <2 * 10(-16)N with integration
time of less than 0.1 ms. The high precision and fast force microscopy results
presented will potentially benefit applications in biosensing, molecular
metrology, subsurface imaging and accelerometry.
PMID- 25118709
TI - Structural characterization of a Gcn5-related N-acetyltransferase from
Staphylococcus aureus.
AB - The Gcn5-related N-acetyltransferases (GNATs) are ubiquitously expressed in
nature and perform a diverse range of cellular functions through the acetylation
of small molecules and protein substrates. Using activated acetyl coenzyme A as a
common acetyl donor, GNATs catalyse the transfer of an acetyl group to acceptor
molecules including aminoglycoside antibiotics, glucosamine-6-phosphate,
histones, serotonin and spermidine. There is often only very limited sequence
conservation between members of the GNAT superfamily, in part, reflecting their
capacity to bind a diverse array of substrates. In contrast, the secondary and
tertiary structures are highly conserved, but then at the quaternary level there
is further diversity, with GNATs shown to exist in monomeric, dimeric, or
tetrameric states. Here we describe the X-ray crystallographic structure of a
GNAT enzyme from Staphylococcus aureus with only low sequence identity to
previously solved GNAT proteins. It contains many of the classical GNAT motifs,
but lacks other hallmarks of the GNAT fold including the classic beta-bulge
splayed at the beta-sheet interface. The protein is likely to be a dimer in
solution based on analysis of the asymmetric unit within the crystal structure,
homology with related GNAT family members, and size exclusion chromatography. The
study provides the first high resolution structure of this enzyme, providing a
strong platform for substrate and cofactor modelling, and structural/functional
comparisons within this diverse enzyme superfamily.
PMID- 25118713
TI - Conducting research and collaborating with researchers: the experience of
clinicians in a residential treatment center.
AB - This paper describes the experience of clinicians in conducting research and
collaborating with academic researchers. As part of clinical routine of a
residential program for adolescent substance abusers, empirical data have been
collected to assess client's needs before and after treatment, improve clinical
practice, and identify barriers to change. Some of the challenges faced and the
benefits learned in conducting these studies are presented. In addition to
highlighting the convergence of research interests between clinicians and
academicians, the conclusion offers general recommendations to foster these
partnerships and solidify the scientific-practitioner model.
PMID- 25118712
TI - Systematics of spiny predatory katydids (Tettigoniidae: Listroscelidinae) from
the Brazilian Atlantic Forest based on morphology and molecular data.
AB - Listroscelidinae (Orthoptera: Tettigoniidae) are insectivorous Pantropical
katydids whose taxonomy presents a long history of controversy, with several
genera incertae sedis. This work focused on species occurring in the Brazilian
Atlantic Forest, one of the world's most threatened biomes. We examined material
deposited in scientific collections and visited 15 conservation units from Rio de
Janeiro to southern Bahia between November 2011 and January 2012, catching 104
specimens from 10 conservation units. Based on morphological and molecular data
we redefined Listroscelidini, adding a new tribe, new genus and eight new species
to the subfamily. Using morphological analysis, we redescribed and added new
geographic records for six species, synonymized two species and built a
provisional identification key for the Atlantic Forest Listroscelidinae.
Molecular results suggest two new species and a new genus to be described,
possibly by the fission of the genus Hamayulus. We also proposed a 500 bp region
in the final portion of the COI to be used as a molecular barcode. Our data
suggest that the Atlantic Forest Listroscelidinae are seriously endangered,
because they occur in highly preserved forest remnants, show high rates of
endemism and have a narrow geographic distribution. Based on our results, we
suggest future collection efforts must take into account the molecular barcode
data to accelerate species recognition.
PMID- 25118714
TI - Drinking pattern, abstention and problem drinking as risk factors for depressive
symptoms: evidence from three urban Eastern European populations.
AB - PURPOSE: To examine whether the frequency and amount of alcohol consumed in binge
drinking sessions, total annual volume of alcohol consumed, problem drinking and
abstaining from alcohol are associated with depressive symptoms in Eastern
Europe. SUBJECTS AND METHODS: Cross-sectional data from a total of 24,381
participants from general population samples of the Czech Republic (N = 7,601),
Russia (N = 6,908) and Poland (N = 9,872) aged 45-69 years in 2002-2005.
Depressive symptoms were defined as >= 16 points on the Centre for
Epidemiological Studies - Depression (CES-D) scale. Several alcohol related
measures were derived using responses from the graduated frequency questionnaire.
Binge drinking was defined at several sex-specific thresholds (ranging from 60+
to 140+ g of ethanol) and two frequencies (at least monthly or weekly). Total
annual alcohol intake in grams was also extracted. Problem drinking was defined
as >= 2 positive answers on the CAGE questionnaire. RESULTS: Problem drinking was
consistently associated with approximately a 2-fold increase in odds of
depressive symptoms across all countries and in both sexes. Abstaining from
alcohol was typically associated with increased odds of depressive symptoms.
Analyses separating lifelong abstainers and former drinkers in the Russian cohort
revealed that this increased odds was driven by former drinkers. Amongst men,
heavy frequent binge drinking was associated with increased odds of depressive
symptoms in the Czech Republic and Poland. In women, heavy infrequent binge
drinking was associated with increased odds of depressive symptoms in Russia and
Poland. Only in Polish men was higher annual volume of alcohol intake associated
with increased odds of depressive symptoms. CONCLUSION: Abstaining from alcohol
and problem drinking were associated with increased odds of depressive symptoms
in these Eastern European populations. Annual volume of alcohol intake as well as
frequency and amount of alcohol consumed in a binge drinking session were less
consistently associated with depressive symptoms.
PMID- 25118715
TI - De novo comparative transcriptome analysis of Acremonium chrysogenum: high-yield
and wild-type strains of cephalosporin C producer.
AB - beta-lactam antibiotics are widely used in clinic. Filamentous fungus Acremonium
chrysogenum is an important industrial fungus for the production of CPC, one of
the major precursors of beta-lactam antibiotics. Although its fermentation yield
has been bred significantly over the past decades, little is known regarding
molecular changes between the industrial strain and the wild type strain. This
limits the possibility to improve CPC production further by molecular breeding.
Comparative transcriptome is a powerful tool to understand the molecular
mechanisms of CPC industrial high yield producer compared to wild type. A total
of 57 million clean sequencing reads with an average length of 100 bp were
generated from Illumina sequencing platform. 22,878 sequences were assembled.
Among the assembled unigenes, 9502 were annotated and 1989 annotated sequences
were assigned to 121 pathways by searching against the Kyoto Encyclopedia of
Genes and Genomes pathway (KEGG) database. Furthermore, we compared the
transcriptome differences between a high-yield and a wild-type strain during
fermentation. A total of 4329 unigenes with significantly different transcription
level were identified, among which 1737 were up-regulated and 2592 were down
regulated. 24 pathways were subsequently determined which involve glycerolipid
metabolism, galactose metabolism, and pyrimidine metabolism. We also examined the
transcription levels of 18 identified genes, including 11 up-regulated genes and
7 down-regulated genes using reverse transcription quantitative -PCR (RT-qPCR).
The results of RT-qPCR were consistent with the Illumina sequencing. In this
study, the Illumina sequencing provides the most comprehensive sequences for gene
expression profile of Acremonium chrysogenum and allows de novo transcriptome
assembly while lacking genome information. Comparative analysis of RNA-seq data
reveals the complexity of the transcriptome in the fermentation of different
yield strains. This is an important public information platform which could be
used to accelerate the research to improve CPC production in Acremonium
chrysogenum.
PMID- 25118716
TI - Skills training of health workers in the use of a non surgical device (PrePex)
for adult Safe Male Circumcision.
AB - BACKGROUND: Safe Male Circumcision (SMC) is a proven approach for partial
protection of men from acquisition of HIV infection. Several sub-Saharan African
countries have a target to circumcise 80% of males aged 15 to 49. The use of
devices such as PrePex would aid scaling up of SMC. Since most health workers
would have no prior experience with use of devices, skills training is needed.
This paper explores a skills transfer model at an urban site in Uganda.
OBJECTIVE: To assess the practicability and feasibility of rapid short duration
training for safe PrePex device use. METHODS: A prospective study, conducted over
8 weeks (August-October 2012) at International Hospital Kampala, an urban Kampala
hospital, examining the performance of various health worker cadres after
training in the use of a non-surgical device (PrePex). The prospective study
obtained approval from the Makerere School of Medicine Research and Ethics
Committee and the Uganda National Council of Science and Technology. If eligible,
and after the subject signed the informed consent form, they were enrolled into
the study. RESULTS: Ten health workers were successfully trained in use of PrePex
during a 3 day non-residential on-the-job training course. After the first three
days of training, the trained health workers performed 561 placements and 529
device removals successfully. Over all adverse events (AE) rates were below <=
2%; however, there were some differences in AE rates across the cadres trained
but not significant (p>0.25 for moderate AEs). CONCLUSION: Rapid training for
safe use of the PrePex device is feasible for the range of health workers
available for SMC in resource limited settings, but among those with past SMC
experience.
PMID- 25118720
TI - A comparison of mid-forehead and axillary temperatures in newborn intensive care.
AB - OBJECTIVE: To evaluate accuracy of mid-forehead (MFH) thermometry compared with
digital axilla (DAT) temperatures in infants in newborn intensive care. STUDY
DESIGN: A comparative study of MFH and DAT temperatures of newborn infants
receiving tertiary-level intensive care. All admissions were considered and the
following exclusion criteria applied: 'in extremis', hypoxic ischemic
encephalopathy or non-English-speaking parents. Foot temperatures, infant and
environmental variables were measured. RESULT: In all, 783 readings were obtained
in 100 infants with a birth weight range 515 to 4885 g (mean 2152 g). The between
person correlation was 0.30 (P < 0.001) and the within-person correlation was
0.52 (P < 0.001). Bland-Altman plots showed wide 95% confidence intervals in the
differences between MFH and DAT measurements (-0.87 to 1.16 degrees C).
Differences were affected by infant variables measured. MFH more accurately
predicted DAT measurements in smaller neonates and were less accurate in neonates
requiring Bubble Continuous Positive Airway Pressure (CPAP). CONCLUSION: MFH
thermometry is not able to replace DAT temperature recording in the newborn
intensive care.
PMID- 25118717
TI - Regulation of microRNA function in somatic stem cell proliferation and
differentiation.
AB - microRNAs (miRNAs) are important modulators of development. Owing to their
ability to simultaneously silence hundreds of target genes, they have key roles
in large-scale transcriptomic changes that occur during cell fate transitions. In
somatic stem and progenitor cells--such as those involved in myogenesis,
haematopoiesis, skin and neural development--miRNA function is carefully
regulated to promote and stabilize cell fate choice. miRNAs are integrated within
networks that form both positive and negative feedback loops. Their function is
regulated at multiple levels, including transcription, biogenesis, stability,
availability and/or number of target sites, as well as their cooperation with
other miRNAs and RNA-binding proteins. Together, these regulatory mechanisms
result in a refined molecular response that enables proper cellular
differentiation and function.
PMID- 25118722
TI - Decreasing abundance, increasing diversity and changing structure of the wild bee
community (Hymenoptera: Anthophila) along an urbanization gradient.
AB - BACKGROUND: Wild bees are important pollinators that have declined in diversity
and abundance during the last decades. Habitat destruction and fragmentation
associated with urbanization are reported as part of the main causes of this
decline. Urbanization involves dramatic changes of the landscape, increasing the
proportion of impervious surface while decreasing that of green areas. Few
studies have investigated the effects of urbanization on bee communities. We
assessed changes in the abundance, species richness, and composition of wild bee
community along an urbanization gradient. METHODOLOGY/PRINCIPAL FINDINGS: Over
two years and on a monthly basis, bees were sampled with colored pan traps and
insect nets at 24 sites located along an urbanization gradient. Landscape
structure within three different radii was measured at each study site. We
captured 291 wild bee species. The abundance of wild bees was negatively
correlated with the proportion of impervious surface, while species richness
reached a maximum at an intermediate (50%) proportion of impervious surface. The
structure of the community changed along the urbanization gradient with more
parasitic species in sites with an intermediate proportion of impervious surface.
There were also greater numbers of cavity-nesting species and long-tongued
species in sites with intermediate or higher proportion of impervious surface.
However, urbanization had no effect on the occurrence of species depending on
their social behavior or body size. CONCLUSIONS/SIGNIFICANCE: We found nearly a
third of the wild bee fauna known from France in our study sites. Indeed, urban
areas supported a diverse bee community, but sites with an intermediate level of
urbanization were the most speciose ones, including greater proportion of
parasitic species. The presence of a diverse array of bee species even in the
most urbanized area makes these pollinators worthy of being a flagship group to
raise the awareness of urban citizens about biodiversity.
PMID- 25118724
TI - Cervical cancer biopsy reporting: a review.
AB - The terminology for reporting human papillomavirus-associated squamous lesions in
the cervix, both in tissue samples and cytology specimens, has suffered from many
changes throughout the last years creating confusion in interpreting cervical
biopsy and cytology reports by clinicians. This review presents a summary and
discussion of the current terminology for reporting results of cervical biopsies
and cytology with emphasis in the lower anogenital squamous terminology consensus
recommendations for tissue specimens and the 2001 Bethesda Workshop for reporting
cytology results. Microscopic features of cervical lesions in tissue samples and
cytology specimens are presented. Biomarkers, including p16 and Ki-67, are
discussed and how they can help the pathologist when dealing with difficult
cases.
PMID- 25118725
TI - Calretinin immunohistochemistry versus improvised rapid Acetylcholinesterase
histochemistry in the evaluation of colorectal biopsies for Hirschsprung disease.
AB - BACKGROUND: Acetylcholinesterase (AChE) histochemistry on rectal mucosal biopsies
accurately diagnoses Hirschsprung disease (HD), but is not widely employed as it
requires special tissue handling and pathologist expertise. Calretinin
immunohistochemistry (IHC) has been reported to be comparable to AChE staining
with the loss of expression correlating with aganglionosis. AIM: The aim was to
evaluate calretinin IHC as a primary diagnostic tool in comparison to the
improvised rapid AChE technique in the diagnosis of HD. MATERIALS AND METHODS: A
total of 74 rectal biopsies (18 fresh frozen - 18 cases, 56 formalin fixed - 33
cases) from 51 cases of suspect HD were evaluated with hematoxylin and
eosin/AChE/Calretinin. Ten biopsies each from ganglionated and aganglionated
segments served as positive and negative controls. Ileal (3), appendiceal (3) and
ring bowel (2) biopsies were also included. Two pathologists blinded to the
clinical details evaluated the histomorphology with AChE and calretinin.
Observations were statistically analyzed and Cohen's k coefficient employed to
assess agreement between two pathologists and calretinin and the AChE. RESULTS:
The study confirmed HD in 26 and non-HD in 25 cases. There were 7 neonates, 5 low
level biopsies and 14 "inadequate" biopsies. The results of calretinin were
comparable with AChE with a statistically significant measure of agreement of k =
0.973 between the two. One false-positive case of HD was noted with calretinin.
The advantages and disadvantages of calretinin versus AChE are discussed.
CONCLUSION: Calretinin is a reliable single immune marker for ruling out HD by
its specific positive mucosal staining of formalin fixed rectal biopsy. The
improvised AChE staining remains indispensable to confirm HD on fresh biopsies
and thus, along with calretinin IHC maximizes the diagnostic accuracy of HD in
difficult cases.
PMID- 25118726
TI - Evaluation of central nervous system metastases with immunohistochemistry
correlation.
AB - CONTEXT: Brain metastases are the most common intracranial neoplasms. They are
often the first symptom of systemic malignancy. Hence, immunohistochemistry (IHC)
is of importance in evaluating the origin of brain metastases. AIMS: The aim was
to detect the primary site of brain metastases and evaluate the role of IHC in
diagnosing the same. MATERIALS AND METHODS: Data of 74 patients of brain
metastases with unknown primary was analyzed. IHC was performed in these cases.
The histopathological findings were correlated with clinical and radiological
data. RESULTS: Of 74 cases in which IHC was done; the most common primary site
was lung (51 cases). Even after applying IHC, the primary could not be diagnosed
in 10 cases. CONCLUSION: Brain metastases are often the first indicator of
systemic malignancy. Lung is the most common primary site in cases with unknown
primary, as deduced by IHC findings.
PMID- 25118727
TI - A histopathological study of liver and biliary remnants in the long-term
survivors (>10 years) of cases of biliary atresia.
AB - CONTEXT: Biliary atresia (BA) is a destructive process affecting both extra- and
intra-hepatic bile ducts leading to fibrosis and obliteration of the biliary tree
and cirrhosis usually within 2 years. Factors influencing the outcome of
portoenterostomy (PE) have not been clearly defined. AIMS: Our aim was to
identify children with no evidence of liver disease 10 years or more after PE and
to compare the pathology of liver and biliary remnants in this group with those
associated with poor outcome. SETTINGS AND DESIGN: Prospective observational
study. MATERIALS AND METHODS: Wedge biopsies of liver and portal remnants, taken
at the time of PE, where available, were reviewed. The parameters studied were -
presence of large bile ducts (>150 MU), degree of fibrosis and bile duct
proliferation (BDP), presence of ductal plate malformation (DPM) and age at
operation. STATISTICAL ANALYSIS USED: Fisher's exact test with Freeman Halton
extension for univariate analysis and Logistic regression analysis as
multivariate analysis. RESULTS: Of 68 cases operated between 1995 and 2001, 14
patients survived >10 years and 54 were associated with poor outcome. Large ducts
were significantly more in survivors (70% vs. 26%, P = 0.02). DPM was not seen in
any of the survivors and was present in 24% of poor outcome group. Fibrosis and
BDP were also significantly less among the survivors (P < 0.001, P = 0.03,
respectively). The mean ages at operation in the two groups were 66.8 and 89.6
days, respectively. CONCLUSION: From this study, we feel that lower degree of
fibrosis and BDP, absence of DPM, presence of large ducts and younger age at
operation were associated with better long-term outcome. Of these, degree of
fibrosis was the most significant factor.
PMID- 25118718
TI - Bidirectional cargo transport: moving beyond tug of war.
AB - Vesicles, organelles and other intracellular cargo are transported by kinesin and
dynein motors, which move in opposite directions along microtubules. This
bidirectional cargo movement is frequently described as a 'tug of war' between
oppositely directed molecular motors attached to the same cargo. However,
although many experimental and modelling studies support the tug-of-war paradigm,
numerous knockout and inhibition studies in various systems have found that
inhibiting one motor leads to diminished motility in both directions, which is a
'paradox of co-dependence' that challenges the paradigm. In an effort to resolve
this paradox, three classes of bidirectional transport models--microtubule
tethering, mechanical activation and steric disinhibition--are proposed, and a
general mathematical modelling framework for bidirectional cargo transport is put
forward to guide future experiments.
PMID- 25118728
TI - A clinicopathological study of interface dermatitis.
AB - BACKGROUND: Interface dermatitis (ID) refers to a pattern of skin reaction
characterized by an inflammatory infiltrate that appears to obscure the dermo
epidermal junction when observed at low power examination and referred to as
lichenoid tissue reaction. A wide range of inflammatory skin diseases exhibits
interface change with considerable overlap of histological features. The aim of
the present study was to study the clinical features and microscopic features of
ID. MATERIALS AND METHODS: The material for the present study consisted of skin
biopsy samples collected from patients attending the outpatient Department of
Dermatology. The study was conducted for a period of 3 years from 2007 to 2010.
During this period, a total of 125 cases was studied. RESULTS: In the present
study, a total of 125 cases of ID was studied which presented clinically as
papulosquamous disorders. Majority of the cases of ID were seen in women (57.6%).
Majority of ID were lichen planus (LP) and its variants (63.2%).
Clinicopathological concordance was seen in 109 cases (87.2%) and discordance in
16 cases (12.8%). CONCLUSION: The mere presence of an interface lichenoid
inflammatory reaction should not be the sole criterion for the diagnosis of LP or
one of its many variants, as now seems to be the case. A clinicopathologic
correlation is absolutely essential for a conclusive diagnosis of ID.
PMID- 25118721
TI - Catecholamine-resistant hypotension and myocardial performance following patent
ductus arteriosus ligation.
AB - OBJECTIVE: We performed a multicenter study of preterm infants, who were about to
undergo patent ductus arteriosus ligation, to determine whether echocardiographic
indices of impaired myocardial performance were associated with subsequent
development of catecholamine-resistant hypotension following ligation. STUDY
DESIGN: A standardized treatment approach for hypotension was followed at each
center. Infants were considered to have catecholamine-resistant hypotension if
their dopamine infusion was > 15 MUg kg(-1)min(-1). Echocardiograms and cortisol
measurements were obtained between 6 and 14 h after the ligation (prior to the
presence of catecholamine-resistant hypotension). RESULT: Forty-five infants were
enrolled, 10 received catecholamines (6 were catecholamine-responsive and 4
developed catecholamine-resistant hypotension). Catecholamine-resistant
hypotension was not associated with decreased preload, shortening fraction or
ventricular output. Infants with catecholamine-resistant hypotension had
significantly lower levels of systemic vascular resistance and postoperative
cortisol concentration. CONCLUSION: We speculate that low cortisol levels and
impaired vascular tone may have a more important role than impaired cardiac
performance in post-ligation catecholamine-resistant hypotension.
PMID- 25118729
TI - Revisiting epidermal growth factor receptor in glioblastoma multiforme: does it
play a role in response to therapy?
AB - BACKGROUND AND AIM: Glioblastoma multiforme (GBM) are the most aggressive class
of cancer of central nervous system with hallmark characteristics that include
rampant proliferation, necrosis, and endothelial proliferation. Epidermal growth
factor receptor (EGFR) has been implicated as the primary contributor to
glioblastoma initiation and succession. The present study was designed to
evaluate EGFR protein expression in GBM as predictor of response to therapy and
survival. MATERIALS AND METHODS: Epidermal growth factor receptor was assessed by
immunohistochemistry as a percentage of positive tumor cells in hot spots (10
high-power fields). The study group comprised of 35 cases of GBM. All cases
underwent surgical resection and subsequently underwent radiotherapy (n = 17) or
radiotherapy with adjuvant temozolomide chemotherapy (n = 18). Immediate response
to therapy was assessed at 3 months using World Health Organization response
evaluation criteria in solid tumors criteria and cases followed up for survival.
RESULTS: Twenty-four cases (68.6%) expressed EGFR while 11/35 (31.4%) cases were
negative. Response to therapy was evident in 21/35 cases (60.0%) and 14/35 were
(40.0%) nonresponders. Mean EGFR protein expression in responders was 37.23 +/-
33.70 and in nonresponders was 59.5 +/- 39.46 (P = 0.542). The percentage of
responders which were EGFR negative was 72.7% and while response in EGFR positive
cases was observed in 54.2%. Mean survival in EGFR positive and negative GBM was
394.37 +/- 189.11 and 420.54 +/- 191.23 days, respectively. CONCLUSION: The EGFR
negative cases appear to respond better to therapy, however, the difference is
not statistically significant (P = 0.298). Further, EGFR protein expression does
not play a definitive role in predicting survival. This is an original study
evaluating EGFR in terms of therapeutic response.
PMID- 25118730
TI - The prognostic significance of bone marrow metastases: evaluation of 58 cases.
AB - BACKGROUND: Bone marrow biopsy is widely used method for diagnosis, follow-up and
staging of hemato-oncologic diseases. This procedure is also used for determining
the bone marrow metastasis in patients with solid tumors. In this study,
clinical, hematological, and pathological features of 58 patients with bone
marrow metastases diagnosed by bone marrow biopsies were examined retrospectively
MATERIALS AND METHODS: Among 3345 bone marrow biopsies performed in our hospital
between January 2006 and August 2013, 58 cases with solid tumor metastasized to
bone marrow were included in this study. RESULTS: Among 58 cases with solid organ
carcinoma metastasis in bone marrow, mean age was 59.9. Thirty-nine cases were
found to have a known primary tumor focus. The most common tumors metastasized to
bone marrow were breast carcinomas (23 patients, 59%), gastric carcinomas (6
patients, 15.3%), prostate carcinomas (4 patients, 10,2%), and lung carcinomas (3
patients, 7.7%), respectively. Nineteen patients were firstly diagnosed from bone
marrow biopsies as metastatic carcinomas. The median overall survival after bone
marrow metastasis was 28 days (95% confidence interval: 7.5-48.4). The median
overall survival difference was not statistically significant between patients
with primary known and unknown tumor (P = 0.973). Statistically significant
difference was observed between the survival of breast cancer and gastric cancer
(P = 0.028). The most common hematologic symptom was the coexistence of anemia
and thrombocytopenia (31%), thrombocytopenia (27.6%) and anemia (20.7%) alone.
The median overall survival difference was statistically significant between
patients who have anemia and thrombocytopenia (P < 0.005). CONCLUSION: Bone
marrow biopsy is an easily accessible, easily applied, a useful procedure for
diagnosing metastatic diseases in patients with hematologic symptoms such as
anemia and thrombocytopenia besides being an uncomfortable procedure for
patients. Furthermore, it is useful in predicting the prognosis and short survey
after diagnosing bone marrow metastasis.
PMID- 25118732
TI - Prevalence of extended spectrum beta-lactamase producing uropathogens and their
antibiotic resistance profile in patients visiting a tertiary care hospital in
central India: Implications on empiric therapy.
AB - CONTEXT: Antimicrobial resistance showed by different uropathogens is one of the
barricades that might hinder a successful treatment. Detection of extended
spectrum beta-lactamase (ESBL) production among uropathogens is an important
marker of endemicity. AIMS: The present prospective study was done to identify
the trends of uropathogens, to find the prevalence of ESBL isolates and to study
the antibiotic resistance profile of the ESBL and non-ESBL uropathogenic
isolates. MATERIALS AND METHODS: This study was conducted in the Department of
Microbiology of a teaching tertiary care hospital from July 2013 to September
2013. All the uropathogenic isolates were identified up to species level by
conventional methods. The prevalence of potential ESBL producers was explored.
Antibiotic resistance test of the urinary isolates was done by disc-diffusion
method and the results were interpreted according to Clinical Laboratory
Standards Institute-2013 guidelines. RESULTS: A total of 670 urine samples from
male and female patients visiting the outpatient department (OPD) and inpatient
department (IPD) of our hospital were collected. A significantly higher number of
IPD and OPD males (55.1% and 55.5%) were found to be culture positive.
Escherichia coli (55.3%) was the most frequently isolated uropathogen followed by
Klebsiella pneumoniae (23%). However, strains of Escherichia coli (41.6%) were
the highest ESBL producing isolates followed by Pseudomonas aeruginosa (36.1%).
ESBL producing isolates were found to be multidrug-resistant when compared to non
ESBL producers. However, excessive drug-resistance among non-ESBL producing
isolates can't be ignored. CONCLUSION: Our study confirms a global trend toward
increased resistance to beta-lactam antibiotics. We emphasize on the formulation
of antibiotic policy for a particular geographical area.
PMID- 25118731
TI - An appraisal of clinicopathological parameters in Japanese encephalitis and
changing epidemiological trends in upper Assam, India.
AB - CONTEXT: Japanese encephalitis (JE), an acute mosquito-borne viral disease, is
one of the leading causes of viral encephalitis in the South-East Asian region.
JE is endemic in Assam. The morbidity and mortality due to JE is significant with
outbreaks every year during the monsoons. AIMS: The aim was to study the
clinicopathological profile of JE; to examine their role in predicting disease
outcome; and to document the increase in the incidence of JE among the adult
population in this region. MATERIALS AND METHODS: Clinically suspected acute
encephalitis syndrome (AES) cases admitted in Assam Medical College and Hospital
during the period of May 2011 to April 2012 were tested by JE virus specific
Immunoglobulin M capture ELISA. STATISTICAL ANALYSIS USED: Data analysis was
performed using SPSS version 16.0. RESULTS: Out of 424 AES cases, 194 were JE
positive. The occurrence of JE in adults was higher (P < 0.001) than the
pediatric age group. The study recorded a high rate of renal dysfunction in JE
cases. A single case of JE induced abortion and two cases of JE
neurocysticercosis co-infections were documented. Regression analysis revealed
that adult population, unconsciousness, paresis and elevated cerebrospinal fluid
protein level were associated with a worse prognosis in JE cases. Mortality in JE
positive cases was higher than the JE negative cases (P = 0.001). CONCLUSION: The
study attempts to highlight the role played by a combination of clinical and
laboratory parameters in assessing the severity and outcome in JE and may help in
directing the limited medical resources toward those that need it the most.
PMID- 25118733
TI - Comparison of severe pneumonia caused by Human metapneumovirus and respiratory
syncytial virus in hospitalized children.
AB - OBJECTIVES: The objective of this study is to compare the incidence and clinical
characteristics of severe pneumonia caused by Human metapneumovirus (hMPV) to
respiratory syncytial virus (RSV) infection in children. PATIENTS AND METHODS: A
total of 151 children hospitalized with severe pneumonia, were tested for hMPV
using reverse-transcription polymerase chain reaction. At the same time, samples
were tested for RSV and other common respiratory viruses. Medical records,
including clinical, laboratory data, and chest radiography findings, were
reviewed for all children. RESULTS: Of the 151 samples, 88 (58.3%) were positive
for respiratory viruses. Of the 88 positive, there were 6 (4.0%) with hMPV, 66
(43.7%) with RSV, 13 (8.6%) with influenza A, 2 (1.3%) with parainfluenza virus
III, 1 (0.7%) with parainfluenza virus I, 1 (0.7%) with adenovirus and 1 (0.7%)
with influenza B. hMPV-infected patients were significantly older than RSV
infected patients (P < 0.001). Children with hMPV pneumonia had fever more
frequently (P = 0.03). Two hMPV-positive patients (33.3%) required admission to
an intensive care unit, and two patients (33.3%) required mechanical ventilation.
The duration of illness was 18.33 +/- 7.09 days. These characteristics of hMPV
infections were similar to patients with RSV infections. CONCLUSION: Human
metapneumovirus is an infrequent viral pathogen causing severe pneumonia in
children. Children with hMPV were older than those with RSV. The disease caused
by hMPV was similar in presentation and severity to RSV, with a minority of
children requiring additional respiratory support.
PMID- 25118734
TI - Prevalence and invasiveness of community-acquired methicillin-resistant
Staphylococcus aureus: a meta-analysis.
AB - BACKGROUND: Reports suggest that the prevalence of community-acquired methicillin
resistant Staphylococcus aureus (CA-MRSA) has increased, and that CA-MRSA is more
virulent than healthcare-associated (HA)-MRSA. AIMS: The aim of this study is to
gain a better understanding of the invasiveness and prevalence of CA-MRSA in
patients; we systematically reviewed the literature by conducting a meta
analysis. MATERIALS AND METHODS: We searched the MEDLINE and PUBMED databases
from the year these databases were established to January 2013. RESULTS: The
pooled CA-MRSA prevalence among 50,737 patients from 33 studies was 39.0% (range,
30.8-47.8%). The pooled CA-MRSA prevalence rates among pediatric and adult
patients with MRSA infection were 50.2% (range, 37.5-62.8%) and 42.3% (range,
16.4-73.3%), respectively. The pooled CA-MRSA prevalence rates of MRSA-infected
patients in Asia, Europe, and North America were 23.1% (range, 12.0-39.8%), 37.4%
(range, 21.1-56.4%), and 47.4% (range, 35.8-59.4%), respectively. Using the
random effects model, we determined that the pooled odds ratio of invasive
infections in CA- and HA-MRSA was 0.30 (95% confidence interval: 0.08-1.10; P =
0.07, test for heterogeneity P < 0.00001). CONCLUSIONS: The prevalence of CA-MRSA
in MRSA infection varied with area and population. No difference in the ability
to cause invasive infections was found between CA- and HA-MRSA. This finding
challenges the view that CA-MRSA is more virulent than HA-MRSA.
PMID- 25118735
TI - Genotype MTBDR plus assay for molecular detection of rifampicin and isoniazid
resistance in Mycobacterium tuberculosis.
AB - AIM: This study was performed for the rapid identification of Mycobacterium
tuberculosis complex and its resistance to rifampicin and isoniazid, directly
from the sputum samples of pulmonary tuberculosis patients. MATERIALS AND
METHODS: A commercially available genotype MTBDR plus assay was used for the
identification and detection of mutations in Mycobacterial isolates. A total of
100 sputum samples of pulmonary tuberculosis patients were analyzed by using the
genotype MTBDR plus assay. The MTBDR plus assay is designed to detect the
mutations in the hotspot region of rpoB gene, katG and regulatory region of inhA
gene. RESULTS: The genotype MTBDR plus assay detected 22% multidrug resistant
(MDR), 2% rifampicin (RMP) monoresistant and 1% isoniazid (INH) monoresistant
isolates. In 22 MDR isolates, the codons most frequently involved in RMP
associated mutations were codon 531 (54.55%), 516 (31.82%) and 526 (13.63%), and
90.90% of MDR isolates showed KatG S315T mutations and 9.1% showed inhA C-15T
mutations associated with INH resistance. CONCLUSION: The new genotype MTBDR plus
assay represents a rapid, reliable tool for the detection of MDR-TB, wherein
results are obtained in 5 h allowing early and appropriate treatment, which is
essential to cut the transmission path and reduce the spread of MDR-TB. The
genotype MTBDR plus assay can readily be included in a routine laboratory work
for the early diagnosis and control of MDR-TB.
PMID- 25118736
TI - Phosphatase and tensin analog expression in arterial atherosclerotic lesions.
AB - CONTEXT: Phosphatase and tensin analog (PTEN) gene mutation has been proven for
pro-inflammatory property and proliferative potential through tyrosine kinase
pathway. We studied mutated PTEN for its pathogenetic association in arterial
atherosclerosis. AIMS: The objective was to study mutation of PTEN by
immunohistochemical method in arterial atherosclerotic lesions and correlate with
grades of atherosclerosis, smooth muscle migration in intima, degree of
inflammation and Framingham heart study risk factors. SETTINGS AND DESIGN: Human,
Prospective Clinical study. MATERIALS AND METHODS: We studied patients with
arterial occlusive disease diagnosed by Doppler ultrasonography over a 2-year
period. Immunohistochemistry was performed with mouse monoclonal antibodies for
PTEN and smooth muscle actin (SMA). STATISTICAL ANALYSIS USED: Chi-square test.
RESULTS AND CONCLUSION: Aorta was the single most common vessel affected (21%).
Mean age of patients studied was 48.6 years and 80% were male. Mutant PTEN was
associated with higher grades of atherosclerotic lesions (P < 0.0001) graded by
American Heart Association classification and with smooth muscle proliferation
and migration in intima (P < 0.0001). No statistically significant association
with the vessel wall inflammation and other risk factors of atherosclerosis.
PMID- 25118737
TI - Loss of chromosome Y in acute lymphoblastic leukemia: age related or neoplastic
phenomenon?
AB - Loss of chromosome Y (LOY) in the bone marrow has long been considered as an age
related phenomenon with an incidence of more than 25% in males beyond the age of
80 years. Though reported as an acquired abnormality in myeloid neoplasms, it has
rarely been described in B-lymphoblastic leukemia which primarily is a disease of
the young. We describe here in three cases of pediatric B-lymphoblastic leukemia
with LOY. Conventional cytogenetic studies and fluorescence in situ hybridization
studies using centromeric probes for chromosome X and Y on peripheral blood
samples ruled out constitutional LOY in all the three cases favoring it to be a
neoplastic phenomenon.
PMID- 25118738
TI - Role of water quality assessments in hospital infection control: experience from
a new oncology center in eastern India.
AB - Water quality assessment and timely intervention are essential for health.
Microbiology, total dissolved solids (TDS) and free residual chlorine were
measured for water quality maintenance in an oncology center in India. Impact of
these interventions over a period of 22 months has been demonstrated with four
cardinal events. Pseudomonas in hospital water was controlled by adequate
chlorination, whereas high TDS in the central sterile supply department water was
corrected by the installation of electro-deionization plant. Contaminated bottled
water was replaced using quality controlled hospital supply. Timely detection and
correction of water-related issues, including reverse osmosis plant was possible
through multi-faceted approach to water quality.
PMID- 25118739
TI - Observations on Citrobacter species from a tertiary care health center with
special reference to multi-drug resistance and presence of CTX-M gene.
AB - BACKGROUND: Citrobacter is an important nosocomial pathogen and its multi-drug
resistant (MDR) isolates are increasingly being reported across the globe. They
are known to produce extended spectrum beta lactamase (ESBL) and harbor CTX-M
gene. OBJECTIVE: The aim was to isolate Citrobacter sp. from clinical specimens,
analyze their MDR status and look for the presence of CTX-M gene. MATERIALS AND
METHODS: In this prospective study, Citrobacter isolates positive for ESBL on
screening, were confirmed by combined disc method along with minimum inhibitory
concentration (MIC) for cefotaxime. In selected cefotaxime resistant isolates,
multiplex polymerase chain reaction was done for blaCTX-M gene. RESULTS: Of 146
Citrobacter sp. isolated, most (73%) were from admitted patients and hospital
stay of >72 h and prior antibiotic intake were the most common associated
factors. Maximum isolates were from pus (41.1%). Citrobacter freundii was the
commonest species (49%) followed by Citrobacter koseri (28%); 79 were ESBL
producers. Seventy were cefotaxime resistant as shown by MIC. blaCTX-M gene was
detected in 15/40 of these isolates, all belonged to CTX-M group 1. CONCLUSION:
Overall incidence of Citrobacter in our setup is low, but they were mostly MDR,
and ESBL production was high, which is a cause of concern. blaCTX-M gene
detection is important because of its rapid transmission to other bacterial
species.
PMID- 25118740
TI - Human parvovirus B19 in Iranian pregnant women: a serologic survey.
AB - BACKGROUND: Parvovirus B19 infection is associated with clinical symptoms that
vary in the spectrum from trivial to severe. The important clinical
manifestations are erythema infectiosum or the fifth disease, transient aplastic
anemia in patients with hemoglobinopathies, acute polyarthralgia syndrome in
adults, hydrops fetalis, spontaneous abortion and stillbirth. Acute infection in
nonimmune pregnant women can lead to fetal hydrops. In view of the many
complications that can result from acute parvovirus B19 infections during
pregnancy, documenting the seroprevalence of anti-parvovirus B19 IgG and its
association with the history of abortion in an Iranian population of pregnant
women would be of value. MATERIALS AND METHODS: Serum samples from 86 pregnant
women were collected between May and September 2011 in West Azerbaijan province
of Iran. Every pregnant woman completed a questionnaire which included age,
history of tattooing, blood transfusion, and abortion. Anti-B19 specific IgG was
detected by using commercial enzyme-linked immunosorbent assays. RESULTS: Anti
B19-specific IgG antibody was detected in (65/86, 75.6%) of pregnant women. The
mean age was 25.56 +/- 5.30 years and three women had a documented history of
blood transfusion (2 of them tested seropositive for B19). 16/18 (88.8%) of women
with a history of abortion were IgG positive. The frequency of abortion sessions
in the seropositive group (25 sessions of abortion: 11 women experienced once, 2
twice, 2 thrice and one 4 times) was 4.03 times greater than abortion in
seronegative group (2 abortions/21 seronegative women). CONCLUSION: Our study
reaffirms previous reports regarding the higher frequency of abortion among anti
B19 IgG seropositive pregnant women and a possible role of this viral infection
in the pathogenesis of abortion.
PMID- 25118741
TI - Metastatic ganglioneuroma: a misnomer.
AB - Neuroblastoma, ganglioneuroblastoma and ganglioneuroma atumors arising from the
neural crest cells. Ganglioneuroma is considered as the most mature amongst the
three and usually has no metastatic potential. Spontaneous maturation of
neuroblastoma into ganglioneuroma is, however, quite well-known. Here, we present
a case of an 8-year-old girl child with evidence of metastasis of ganglioneuroma
into a lymph node.
PMID- 25118742
TI - Primary extrauterine endometrial stromal sarcoma: Located in pelvic and abdominal
tissue and arising in endometriosis.
AB - Primary extrauterine endometrial stromal sarcoma is a rare tumor and it is
infrequently associated with endometriosis. We are reporting a case of this
unusual tumor in a 42-year-old female who presented with multiple nodules of
tumor in the abdomen and pelvis and with metastases in para-aortic lymph nodes.
The right parametrium, in addition, had a focus of endometriosis, which was
contiguous with the tumor, confirming its origin.
PMID- 25118743
TI - Leiomyoadenomatoid tumor of the uterus: report of a rare entity and review of the
literature.
AB - Adenomatoid tumor occurs in the testicular spermatic cord and ejaculatory duct in
males and in the fallopian tube and uterus in the females. These are usually
small, benign lesions and are mostly incidental findings. Leiomyo-adenomatoid
tumor (LMAT) is a variant of adenomatoid tumor, where in the smooth muscle
component is predominant. Only nine cases of LMAT are reported so far in the
English literature. We report one case and review the nine cases reported so far.
PMID- 25118744
TI - Clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres.
AB - Clear cell myomelanocytic tumors (CCMTs) of the falciform ligament/ligamentum
teres are extremely rare. CCMTs are a variant of perivascular epithelioid cell
tumors. We present a case of hepatic CCMT in a 54-year-old woman with abdominal
pain. The patient had an 8.8 cm well-demarcated tumor in the right lobe of the
liver. Contrast-enhanced computed tomography showed a heterogeneous mass that
enhanced significantly in the arterial and portal venous phases, and was less
enhanced in the delayed phase. The patient underwent a right hemihepatectomy and
cholecystectomy. The tumor cells had clear to slightly eosinophilic cytoplasm,
vesicular nuclei, and were positive for HMB-45 and smooth muscle actin. The
patient had no recurrence after 36 months follow-up. A review of the literature
identified 10 hepatic CCMTs. Hepatic CCMTs are usually benign tumors of young
women that present as large masses located in the right lobe of the liver.
PMID- 25118746
TI - Cutaneous myxoma: an important clue to Carney complex.
AB - A 22-year-old male became unconscious and was found to have left-sided weakness
and facial asymmetry. Previously, he had up to 35 excisions for subcutaneous
swellings all over the body, commencing at age 6 years. Examination revealed
small nodular skin lesions on the neck, the eyelid and hard palate. Two
dimensional echocardiography showed two left atrial masses. Histopathological
examination of the subcutaneous lesions showed cutaneous myxomas with a prominent
epithelial component. The left atrial masses were also myxomas. The case attempts
to highlight the importance of histopathological examination of subcutaneous
swellings. Cutaneous and subcutaneous manifestations, including cutaneous
myxomas, are among the earliest presentations in Carney's complex and may herald
potentially fatal cardiac myxoma. The prominent epithelial component in cutaneous
myxomas may be confusing and cause diagnostic difficulties.
PMID- 25118745
TI - Clear cell myoepithelial carcinoma ex pleomorphic adenoma.
AB - Pleomorphic adenoma is the most common epithelial neoplasm of lacrimal gland. A
clear cell myoepithelial carcinoma arising in the background of pleomorphic
adenoma is common in the salivary glands but very rare in the lacrimal glands. We
report the case of a 27 year old man whose lacrimal gland pleomorphic adenoma
recurred several times over a period of four years and ultimately evolved into a
clear cell myoepithelial carcinoma ex pleomorphic adenoma.
PMID- 25118747
TI - Epstein-Barr virus-associated lymphoepithelioma-like gastric carcinoma located on
gastric high body: two case reports.
AB - Lymphoepithelioma-like gastric carcinoma (LELGC) is a rare neoplasm of the
stomach with an incidence of 1-4% of all gastric cancers. It is characterized by
the presence of a lymphoid stroma with cells arranged primarily in micro
alveolar, thin trabecular, and primitive tubular patterns or isolated cells. It
is one of the histological patterns observed in patients with Epstein - Barr
virus (EBV)-associated gastric carcinoma (EBVaGC). In situ hybridization was
usually used to confirm the presence of EBV. There are two types of EBVaGC,
LELGC, and ordinary type. Approximately, 15-25% of EBVaGC exhibit the LELGC
pattern. Here, we described two cases of LELGC and the related literatures were
reviewed as well. The two cases were submucosal mass from a 59- or 63-year-old
man. We found LELGC has special clinicopathologic features and protein expression
profile. This should promote us to make a true diagnosis.
PMID- 25118748
TI - Diagnostic dilemma in myoepithelial carcinoma of cheek.
AB - Myoepithelial carcinoma (MC) is a rare neoplasm of the salivary gland generally
occurring in the parotid gland and rarely in the minor salivary glands. It poses
a diagnostic challenge on fine-needle aspiration (FNA) cytology because it can
show different cell types and lack clear features of malignancy. This can lead to
a range of differential diagnosis on cytology. The diagnostic difficulty can be
compounded if the lesion is present at an unusual site. A 41-year-old male
presented with a recurrent swelling on the check since 2 years with a prior
history of pleomorphic adenoma (PA) at the same site 8 years back. FNA was
performed and a diagnosis of recurrent PA or myoepithelial cell neoplasm was
given. Final diagnosis was made on histology and immunohistochemistry studies and
reported as MC of minor salivary gland originating within PA. Pathologist should
be aware of the occurrence of MC at the sites of the minor salivary glands in the
oral cavity and its wide morphologic spectrum to make a confident diagnosis of MC
preoperatively.
PMID- 25118749
TI - Cytoplasmic-anti-neutrophil cytoplasmic antibodies targeting myeloperoxidase in
Wegener's granulomatosis: a rare phenomenon.
AB - Wegener's granulomatosis (WG) patients can rarely have antineutrophil cytoplasmic
antibodies (ANCAs) directed against myeloperoxidase (MPO), producing a
cytoplasmic pattern on indirect immunofluorescence (IIF). This has important
implications in the diagnosis and pathophysiology of the disease. We present to
you a report of three cases of WG, demonstrating a cytoplasmic-ANCA pattern on
indirect IIF, but directed against MPO. It is necessary to diagnose a patient
taking into account both the autoimmune test results and the clinical features.
PMID- 25118750
TI - Nonhemophilic hemosiderotic synovitis of the knee: a case report and review of
literature.
AB - Synovium is specialized mesenchymal tissue lining the inner surface of the joint
capsule and is the site for a series of pathologic processes that are
characteristic, and in some cases specific, to this distinctive tissue.
Hemosiderotic synovitis is a rare and inadequately defined synovial proliferative
disorder, which develops with recurrent hemorrhages in the joint. The most
affected joint from bleeding is the knee whatever the etiology is. Repeated
hemarthrosis may produce significant structural alteration of joints leading to
chronic osteoarthritis. The most common cause is hereditary clotting factor
deficiency diseases like hemophilia. We report a rare case of nonhemophilic
hemosiderotic synovitis of the knee joint, in which the patient lacks history of
any bleeding diathesis. Its definitive diagnosis was possible only by
histopathological examination. The prompt recognition of this distinct subtype of
hemosiderotic synovitis and awareness of underlying causes should lead to earlier
diagnosis, appropriate therapy, less joint destruction, and better outcomes.
PMID- 25118751
TI - Spurious platelet count due to cryoglobulins in a patient with smoldering
myeloma.
AB - Use of automated hematology analyzers for routine blood count reporting has
increased the reproducibility and accuracy of test results. However, at times,
these instruments may generate spurious test results. Such results can result in
inappropriate investigations or treatment decisions in patients. Spuriously
normal or high platelet counts carry the risk of under diagnosis of the true
thrombocytopenia with adverse clinical implications. We present a patient with
smoldering myeloma with spurious platelet count due to cryoglobulins.
PMID- 25118752
TI - Omental sclerosing extramedullary hematopoietic tumors in Janus kinase-2 negative
myelofibrosis: caveat at frozen section.
AB - Sclerosing extramedullary hematopoietic tumors (SEMHTs) are associated with
chronic myeloproliferative neoplasms. These extremely rare mass lesions were
first described in kidney and peritoneum. On histopathology, they are
characterized by sclerosis, entrapped fat, atypical megakaryocytes with myeloid
and erythroid elements. Only approximately ten cases have been subsequently
reported in orbit, lacrimal system, liver, omentum, and skin. The authors present
a case of SEMHTs as incidentally detected omental nodules, while the patient was
undergoing splenectomy for Janus kinase-2 negative myelofibrosis. The authors
postulate their origin in omentum-associated lymphoid tissue; and highlight the
diagnostic dilemma presented by SEMHTs at frozen section.
PMID- 25118753
TI - Aggressive natural killer-cell leukemia: classical presentation of a rare
disease.
AB - Aggressive natural killer-cell leukaemia is a rare aggressive form of natural
killer-cell neoplasm. We report a case of a 40-year-old male who presented with
jaundice, raised blood counts,generalised lymphadenopathy and hepatosplenomegaly.
The diagnosis was established by flow cytometric analysis of bone marrow
aspirate. The patient, however, succumbed to his illness within 2 weeks of
starting chemotherapy. To the best of our knowledge, this is the third reported
case from India.
PMID- 25118754
TI - Hospital acquired urinary tract infection by multidrug-resistant Brevundimonas
vesicularis.
AB - Infections caused by Brevundimonas vesicularis, a nonfermenting Gram-negative
bacterium, are very rare. Here, we report the first case of multidrug-resistant
hospital acquired urinary tract infection by B. vesicularis. Patient was
successfully treated with antimicrobial therapy with piperacillin-tazobactam and
amikacin.
PMID- 25118755
TI - Extended spectrum beta lactamase producing Proteus penneri: a rare missed
pathogen?
AB - Indole negative Proteus species are invariably incorrectly identified as Proteus
mirabilis, often missing out isolates of Proteus penneri. We report a case of
extended spectrum beta lactamase producing and multidrug-resistant P. penneri
isolated from pus from pressure sore of a patient of road traffic accident.
Correct and rapid isolation and identification of such resistant pathogen are
important as they are significant nosocomial threat.
PMID- 25118756
TI - Massive pleural effusion due to paragonimiasis: biochemical, cytological, and
parasitological findings.
AB - Paragonimiasis is an important food-borne parasitic zoonosis caused by trematode
species of the genus, Paragonimus occurring in many parts of the world except in
Australia and Antarctica. In India, it is an emerging parasitic disease, which is
endemic in the northeast states where people have a common practice of eating raw
or inadequately cooked freshwater crabs. In these states, Paragonimus
heterotremus has been identified as the major causative agent of the human
paragonimiasis. The most common clinical form of the disease is pulmonary
paragonimiasis; however, extra-pulmonary manifestations are not uncommon. Here,
we report a case of primary massive unilateral pleural effusion due to
paragonimiasis. The diagnosis was confirmed by finding Paragonimus ova in the
pleural fluid. The patient was successfully treated with repeated thoracocentesis
and a course of praziquantel.
PMID- 25118757
TI - Panoramic images of testicular feminizing syndrome.
PMID- 25118758
TI - Intrathoracic extramedullary hematopoiesis in E-beta thalassemia.
PMID- 25118759
TI - Cutaneous images of interest of fascioliasis from India.
PMID- 25118760
TI - Quiz 3/2014.
PMID- 25118761
TI - Quiz 4/2014.
PMID- 25118762
TI - Mucosa associated lymphoid tissue lymphoma of gallbladder: a rare presentation.
PMID- 25118763
TI - Paratesticular myxofibrosarcoma.
PMID- 25118764
TI - Calcifying fibrous tumor of the rectum: a case report.
PMID- 25118765
TI - Barium granuloma mimicking carcinoma rectum: an unusual presentation.
PMID- 25118766
TI - Nodal metastatic, undifferentiated nasopharyngeal carcinoma and classical Hodgkin
lymphoma: age old mimics.
PMID- 25118767
TI - Gastric glomus tumor: a brief report.
PMID- 25118768
TI - Solitary angiokeratoma of tongue: a rare entity clinically mistaken as a
malignant tumor.
PMID- 25118769
TI - Relevance of synovial cells in gouty tophus on fine needle aspiration cytology.
PMID- 25118770
TI - Acute megakaryoblastic leukemia M7 presenting with extreme myelofibrosis.
PMID- 25118771
TI - Histological identification of Entomophthoromycosis in biopsy samples is
required.
PMID- 25118772
TI - Intestinal spirochetosis: a disease or an interesting finding.
PMID- 25118773
TI - Commentary on intestinal spirochetosis.
PMID- 25118774
TI - Comparison of Clinical and Laboratory Standards Institute 2008 and 2010
guidelines in interpreting susceptibility of enterobacteriaceae isolates.
PMID- 25118775
TI - Isolated nasal chromoblastomycosis.
PMID- 25118776
TI - Aeromonas species isolated from a case of meningitis.
PMID- 25118777
TI - Spectrum of lymph node pathology: inadequate data, challenging issues.
PMID- 25118778
TI - Slide seminars: is it the right way to test the students' surgical pathology
knowledge?
PMID- 25118779
TI - Vaccination management and vaccination errors: a representative online-survey
among primary care physicians.
AB - BACKGROUND: Effective immunizations require a thorough, multi-step process, yet
few studies comprehensively addressed issues around vaccination management.
OBJECTIVES: To assess variations in vaccination management and vaccination errors
in primary care. METHODS: A cross sectional, web-based questionnaire survey was
performed among 1157 primary physicians from North Rhine-Westphalia, Germany: a
representative 10% random sample of general practitioners (n = 946) and all
teaching physicians from the University Duisburg-Essen (n = 211). Four quality
aspects with three items each were included: patient-related quality (patient
information, patient consent, strategies to increase immunization rates), vaccine
related quality (practice vaccine spectrum, vaccine pre-selection, vaccination
documentation), personnel-related quality (recommendation of vaccinations,
vaccine application, personnel qualification) and storage-related quality
(storage device, temperature log, vaccine storage control). For each of the four
quality aspects, "good quality" was reached if all three criteria per quality
aspect were fulfilled. Good vaccination management was defined as fulfilling all
twelve items. Additionally, physicians' experiences with errors and nearby-errors
in vaccination management were obtained. RESULTS: More than 20% of the physicians
participated in the survey. Good vaccination management was reached by 19% of the
practices. Patient-related quality was good in 69% of the practices, vaccine
related quality in 73%, personnel-related quality in 59% and storage-related
quality in 41% of the practices. No predictors for error reporting and good
vaccination management were identified. CONCLUSIONS: We identified good results
for vaccine- and patient-related quality but need to improve issues that revolve
around vaccine storage.
PMID- 25118781
TI - Deep penetrating nevus-like borderline tumors: A unique subset of ambiguous
melanocytic tumors with malignant potential and normal cytogenetics.
AB - BACKGROUND: Deep penetrating nevi (DPN) are a relatively uncommon subtype of
melanocytic nevi. A small subset of these lesions exhibit atypical features
(cytologic and architectural atypia, mitotic activity) seen in melanoma. These
lesions we term the deep penetrating nevus-like borderline tumor. Unequivocal
melanomas can show overlapping morphologic features of DPN, which have been
termed plexiform melanomas. PATIENTS AND METHODS: 40 cases of DPN-like borderline
tumor were identified along with 6 cases of plexiform melanoma. Clinical follow
up was obtained, along with cytogenetic analysis in the form of fluorescent in
situ hybridization (FISH) and/or comparative genomic hybridization (CGH).
RESULTS: The DPN-like borderline tumor cases included 24 females and 16 males. Of
sentinel lymph node biopsies performed, 1/3 of cases showed lymph node
involvement. All patients where an aggressive clinical approach was adopted
remain free of disease. All 6 DPN-like borderline tumor cases tested by CGH
showed normal cytogenetics, as did 7 of 9 cases tested by FISH. Of the plexiform
melanomas, 4/6 patients died of disease. In 3 cases there was morphologic
progression from a DPN-like borderline tumor to overt melanoma. In one case of
progression, cytogenetics was normal in the DPN-like borderline tumor and then
abnormal in the progressed melanoma. CONCLUSION: DPN-like borderline tumors are
melanocytic tumors associated with a high incidence of regional lymph node
disease and exhibiting the potential for melanoma progression despite a normal
cytogenetic profile. Patients with these lesions should be aggressively managed,
with at least complete re-excision and consideration of sentinel node biopsy,
regardless of cytogenetic data.
PMID- 25118782
TI - Preventive effects of Escherichia coli strain Nissle 1917 with different courses
and different doses on intestinal inflammation in murine model of colitis.
AB - OBJECTIVE: To analyze the in vivo effect of Escherichia coli Nissle 1917 (EcN)
with different courses and different doses to Sprague-Dawley rats with
trinitrobenzene sulfonic acid (TNBS)-induced colitis. METHODS: The probiotic was
orally administered with different courses of treatment (with or without pre
administration) and different doses (10(7)-10(9) CFU/day) to Sprague-Dawley rats
with TNBS-induced colitis. Therapeutic effects, levels of cytokine in serum, mRNA
and protein expression were analyzed. RESULTS: Oral EcN administration after TNBS
induced improved colitis dose dependently. In parallel, a reduction of disease
activity index and colonic MPO activity together with a decreased level of TNF
alpha and a trend of increased IL-10 expression was detected. Pre-administration
of 10(7)CFU/day EcN to TNBS-treated rats resulted in a significant protection
against inflammatory response and colons isolated from these rats exhibited a
more pronounced expression of ZO-1 than the other groups. In the group of pre
administration of 10(9)CFU/day, the condition was not improved but deteriorated.
CONCLUSIONS: This study convincingly demonstrates that pre-administration of
probiotic EcN with low dose is able to protect colitis of rats and mediate up
regulation of ZO-1 expression, but long-term of high-dose EcN may do harm to
colitis.
PMID- 25118785
TI - Relevance of intracellular polarity to accuracy of eukaryotic chemotaxis.
AB - Eukaryotic chemotaxis is usually mediated by intracellular signals that tend to
localize at the front or back of the cell. Such intracellular polarities
frequently require no extracellular guidance cues, indicating that spontaneous
polarization occurs in the signal network. Spontaneous polarization activity is
considered relevant to the persistent motions in random cell migrations and
chemotaxis. In this study, we propose a theoretical model that connects
spontaneous intracellular polarity and motile ability in a chemoattractant
solution. We demonstrate that the intracellular polarity can enhance the accuracy
of chemotaxis. Chemotactic accuracy should also depend on chemoattractant
concentration through the concentration-dependent correlation time in the
polarity direction. Both the polarity correlation time and the chemotactic
accuracy depend on the degree of responsiveness to the chemical gradient. We show
that optimally accurate chemotaxis occurs at an intermediate responsiveness of
intracellular polarity. Experimentally, we find that the persistence time of
randomly migrating Dictyostelium cells depends on the chemoattractant
concentration, as predicted by our theory. At the optimum responsiveness, this
ameboid cell can enhance its chemotactic accuracy tenfold.
PMID- 25118783
TI - TLR4 inhibition impairs bacterial clearance in a therapeutic setting in murine
abdominal sepsis.
AB - OBJECTIVE AND DESIGN: To investigate the therapeutic effect of E5564 (a
clinically used TLR4 inhibitor) in murine abdominal sepsis elicited by
intraperitoneal infection with a highly virulent Escherichia coli in the context
of concurrent antibiotic therapy. METHODS: Mice were infected with different
doses (~2 * 10(4)-2 * 10(6) CFU) of E. coli O18:K1 and treated after 8 h with
ceftriaxone 20 mg/kg i.p. combined with either E5564 10 mg/kg i.v. or vehicle.
For survival studies this treatment was repeated every 12 h. Bacterial loads and
inflammatory parameters were determined after 20 h in peritoneal lavage fluid,
blood, liver and lung tissue. Plasma creatinin, AST, ALT and LDH were determined
to assess organ injury. RESULTS: E5564 impaired bacterial clearance under the
antibiotic regime after infection with a low dose E. coli (1.7 * 10(4) CFU) while
renal function was slightly preserved. No differences were observed in bacterial
load and organ damage after infection with a tenfold higher (1.7 * 10(5) E. coli)
bacterial dose. While treatment with E5564 slightly attenuated inflammatory
markers provoked by the sublethal doses of 104-105 E. coli under the antibiotic
regime, it did not affect lethality evoked by infection with 1.7 * 106 E. coli.
CONCLUSIONS: The impact of TLR4 inhibition during abdominal sepsis by virulent E.
coli bacteria is only beneficial at low infection grade at cost of bactericidal
activity.
PMID- 25118786
TI - Joep MA Lange.
PMID- 25118784
TI - Blockade of proteinase-activated receptor 4 inhibits neutrophil recruitment in
experimental inflammation in mice.
AB - OBJECTIVE AND DESIGN: The activation of proteinase-activated receptors (PARs) has
been implicated in the development of important hallmarks of inflammation,
including in vivo leukocyte recruitment; however, its role in the regulation of
leukocyte migration in response to inflammatory stimuli has not been elucidated
until now. Here, we examined the effects of the PAR4 antagonist YPGKF-NH 2 (tcY
NH2) on neutrophil recruitment in experimentally induced inflammation. METHODS:
BALB/c mice were intrapleurally injected with tcY-NH2 (40 ng/kg) prior to
intrapleural injection of carrageenan (Cg) or neutrophil chemoattractant CXCL8;
the number of infiltrating neutrophils was evaluated after 4 h, and KC production
was assessed at different times after Cg injection. Neutrophil adhesion and
rolling cells were studied using a brain circulation preparation 4 h after the Cg
or CXCL8 challenge in tcY-NH2-treated mice. RESULTS: PAR4 blockade inhibited
CXCL8- and Cg-induced neutrophil migration into the pleural cavity of BALB/c mice
and reduced neutrophil rolling and adherence. Surprisingly, PAR4 blockade
increased the level of KC in response to carrageenan. CONCLUSION: These results
demonstrated that PAR4 blockade impairs neutrophil migration in vivo, suggesting
that PAR4 plays an important role in the regulation of inflammation, at least in
part because of its ability to inhibit the actions of the neutrophil
chemoattractant CXCL8.
PMID- 25118787
TI - A monoclonal antibody against PMEL.
AB - PMEL, also known as Pmel17 or gp100, is a melanocyte-specific glycoprotein that
is essential for the formation of stage II melanosomes. As it has a highly
restricted expression pattern in normal tissues and a transient presence on the
cell surface, PMEL is believed to be a potential target for antibody drug
conjugate therapy in some pigmentary diseases. The production of a high
specificity and high affinity monoclonal antibody against human PMEL was helpful
for the antibody drug conjugate therapy study. In the present study, monoclonal
antibodies (MAbs) against PMEL were obtained by immunizing BALB/c mice with the
recombinant PMEL-GST fusion protein. Three mAbs (A3F, G11B, and J7E) with a titer
of 1:6000, 1:10,000, and 1:3000, respectively, were obtained. Immunoglobulin
subclass assay revealed that A3F was IgG2b, G11B was IgG1, and J7E was IgG2a.
Specificity analysis by Western blotting demonstrated that A3F and J7E cross
reacted with GPNMB or LAMP; however, G11B reacted with PMEL only.
Immunohistochemistry experiments showed that G11B could bind human PMEL antigen
in normal skin. Flow cytometry assay demonstrated that G11B could bind to the
surface of PMEL positive melanoma cells but not PMEL negative cells. Taken
together, these results show that this G11B provides a useful tool for the
antibody drug conjugate therapy study in some pigmentary diseases.
PMID- 25118788
TI - Vitamin D status among children and adolescents on anticonvulsant drugs in
southern Switzerland.
AB - INTRODUCTION: It is recognised that vitamin D status is often inadequate (<50
nmol/l) in epileptic children, mainly because some anticonvulsant drugs induce
the enzymes responsible for its metabolism. The purpose of the present study was
to address vitamin D status among children and adolescents treated with
anticonvulsant drugs and control subjects who reside in southern Switzerland, a
high solar radiation region. METHODS: Between January and May 2013, total serum
25-hydroxyvitamin D was assessed by liquid chromatography-tandem mass
spectrometry in 58 children and adolescents with epilepsy and 29 controls
residing in southern Switzerland. Dark-skinned individuals, females wearing dress
styles covering practically the whole body and subjects with body mass index
>=85th percentile for age and sex were excluded. RESULTS: Concentration of serum
25-hydroxyvitamin D was similar in epilepsy patients (48 [37-62] nmol/l; median
and interquartile range) and controls (53 [47-64] nmol/l). An inadequate serum 25
hydroxyvitamin D concentration was common both among patients (55%) and control
subjects (34%). Serum 25-hydroxyvitamin D was significantly lower among patients
treated with anticonvulsant drugs that induce the metabolism of vitamin D (30 [21
51] nmol/l) than among the remaining patients (51 [40-65] nmol/l) and controls.
CONCLUSIONS: The present study indicates a relevant tendency towards inadequate
vitamin D status among children with and without anticonvulsant drug management
who reside in southern Switzerland. This tendency is more prominent in patients
treated with anticonvulsant drugs that induce the metabolism of 25-hydroxyvitamin
D.
PMID- 25118789
TI - The pharmacokinetics, efficacy, safety, and ease of use of a novel portable
metered-dose cannabis inhaler in patients with chronic neuropathic pain: a phase
1a study.
AB - Chronic neuropathic pain is often refractory to standard pharmacological
treatments. Although growing evidence supports the use of inhaled cannabis for
neuropathic pain, the lack of standard inhaled dosing plays a major obstacle in
cannabis becoming a "main stream" pharmacological treatment for neuropathic pain.
The objective of this study was to explore the pharmacokinetics, safety,
tolerability, efficacy, and ease of use of a novel portable thermal-metered-dose
inhaler (tMDI) for cannabis in a cohort of eight patients suffering from chronic
neuropathic pain and on a stable analgesic regimen including medicinal cannabis.
In a single-dose, open-label study, patients inhaled a single 15.1 +/- 0.1 mg
dose of cannabis using the Syqe Inhaler device. Blood samples for Delta(9)
tetrahydrocannabinol (THC) and 11-hydroxy-Delta(9)-THC were taken at baseline and
up to 120 minutes. Pain intensity (0-10 VAS), adverse events, and satisfaction
score were monitored following the inhalation. A uniform pharmacokinetic profile
was exhibited across all participants (Delta(9)-THC plasma Cmax +/- SD was 38 +/-
10 ng/mL, Tmax +/- SD was 3 +/- 1 minutes, AUC0->infinity +/- SD was 607 +/- 200
ng.min/mL). Higher plasma Cmax increase per mg Delta(9)-THC administered (12.3
ng/mL/mg THC) and lower interindividual variability of Cmax (25.3%), compared
with reported alternative modes of THC delivery, were measured. A significant 45%
reduction in pain intensity was noted 20 minutes post inhalation (P = .001),
turning back to baseline within 90 minutes. Tolerable, lightheadedness, lasting
15-30 minutes and requiring no intervention, was the only reported adverse event.
This trial suggests the potential use of the Syqe Inhaler device as a smokeless
delivery system of medicinal cannabis, producing a Delta(9)-THC pharmacokinetic
profile with low interindividual variation of Cmax, achieving pharmaceutical
standards for inhaled drugs.
PMID- 25118790
TI - Failure of dabigatran and rivaroxaban to prevent thromboembolism in
antiphospholipid syndrome: a case series of three patients.
AB - Direct oral factor inhibitors (DOFIs) are an attractive alternative to vitamin K
antagonists (VKA) for the treatment of patients with antiphospholipid syndrome
(APS). In the absence of prospective, randomised trial data, reports of
therapeutic failures in clinical practice alert clinicians to potential
limitations of DOFI therapy for this indication. Data for all cases were
collected from a centralised system that contains complete medical records of all
patients treated and followed at Mayo Medical Center. We present here three
consecutive APS patients who had had no thromboembolism recurrence on warfarin
but were switched to DOFIs. The diagnosis of APS was established according to
currently recommended criteria. The three cases were as follows: A woman with
primary APS developed thrombotic endocarditis with symptomatic cerebral emboli
after transition to dabigatran. A second woman with primary APS experienced
ischemic arterial strokes and right transverse-sigmoid sinus thrombosis after
conversion to rivaroxaban. A man with secondary APS suffered porto-mesenteric
venous thrombosis after switching to rivaroxaban. None of these patients had
failed warfarin prior to the transition to DOFIs. Based on these three cases, we
advocate caution in using DOFIs for APS patients outside of a clinical trial
setting, until further data becomes available.
PMID- 25118791
TI - Acquisition of the stop-spirant alternation in bilingual Mexican Spanish-English
speaking children: theoretical and clinical implications.
AB - The purpose of this study was to identify characteristics of typical acquisition
of the Mexican Spanish stop-spirant alternation in bilingual Spanish-English
speaking children and to shed light on the theoretical debate over which sound is
the underlying form in the stop-spirant allophonic relationship. We predicted
that bilingual children would acquire knowledge of this allophonic relationship
by the time they reach age 5;0 (years;months) and would demonstrate higher
accuracy on the spirants, indicating their role as the underlying phoneme. This
quasi-longitudinal study examined children's single word samples in Spanish from
ages 2;4-8;2. Samples were phonetically transcribed and analyzed for accuracy,
substitution errors and acoustically for intensity ratios. Bilingual children
demonstrated overall higher accuracy on the voiced stops as compared to the
spirants. Differences in substitution errors across ages were found and acoustic
analyses corroborated perceptual findings. The clinical implication of this
research is that bilingual children may be in danger of overdiagnosis of speech
sound disorders because acquisition of this allophonic rule in bilinguals appears
to differ from what has been found in previous studies examining monolingual
Spanish speakers.
PMID- 25118792
TI - Metformin combined with p38 MAPK inhibitor improves cisplatin sensitivity in
cisplatin-resistant ovarian cancer.
AB - The aim of the present study was to determine the effects of metformin, combined
with a p38 mitogen-activated protein kinase (MAPK) inhibitor, on the sensitivity
of cisplatin-resistant ovarian cancer to cisplatin. The expression and
distribution of phosphorylated p38 MAPK (P-p38 MAPK) was confirmed in drug
resistant and primary ovarian cancer tissues by immunohistochemistry and western
blotting. A bromodeoxyuridine ELISA kit was used to analyze the effects of
metformin, SB203580, a p38 MAPK inhibitor, and metformin combined with SB203580,
on the cell proliferation of SKOV3/DDP cisplatin-resistant ovarian cancer cells.
The protein expression of P-p38 MAPK was significantly higher in cisplatin
resistant ovarian cancer, as compared with the primary ovarian cancer tissues.
Metformin combined with SB203580 significantly enhanced the sensitivity of
SKOV3/DDP cells to cisplatin. In conclusion, the p38 MAPK signaling pathway may
be associated with cisplatin-resistant ovarian cancer. Metformin, combined with
the p38 MAPK inhibitor, significantly increased the sensitivity of SKOV3/DDP
cells to cisplatin treatment.
PMID- 25118793
TI - Proteinuria is associated with neurocognitive impairment in antiretroviral
therapy treated HIV-infected individuals.
AB - BACKGROUND: Proteinuria is a marker of vascular dysfunction that predicted
increased cardiovascular mortality and is associated with neurocognitive
impairment (NCI) in population-based studies. We examined associations between
proteinuria and HIV-associated NCI. METHODS: Multivariable logistic regression
was used to examine associations between NCI at the first neurocognitive
assessment (baseline) and simultaneous, clinically significant proteinuria [as
random spot urine protein-to-creatinine ratios (UP/Cr) >=200 mg/g] in a
prospective multicenter observational cohort study. Generalized estimating
equations were used to examine associations between baseline proteinuria and
subsequent NCI among subjects without NCI at baseline. NCI was defined as a Z
score, derived from the combination of normalized scores from the Trailmaking A
and B and the Wechsler Adult Intelligence Scale-Revised Digit Symbol tests.
RESULTS: A total of 1972 subjects were included in this analysis. Baseline
proteinuria was associated with increased odds of NCI [odds ratio (OR): 1.41, 95%
confidence interval (CI): 1.08 to 1.85; P = 0.01] and with subsequent NCI among
subjects without NCI at baseline (OR: 1.39, 95% CI: 1.01 to 1.93; P = 0.046) in
multivariable models adjusted for risk factors and potential confounders. Similar
associations were evident when these analyses were limited to visits at which
time study subjects maintained plasma HIV RNA levels <200 copies per milliliter.
CONCLUSIONS: The association between proteinuria and NCI observed in this study
adds to a growing body of evidence implicating contributions by vascular disease
to NCI in antiretroviral treated individuals. Studies examining interventions
that improve vascular function are warranted.
PMID- 25118794
TI - Feasibility and preliminary efficacy of a web-based smoking cessation
intervention for HIV-infected smokers: a randomized controlled trial.
AB - OBJECTIVE: To evaluate the feasibility and preliminary efficacy of a Web-based
tobacco treatment for persons living with HIV (PLWH). DESIGN: Prospective,
randomized controlled trial. SETTING: HIV-care center in the Bronx, New York.
SUBJECTS: Eligibility criteria included HIV infection, current tobacco usage,
interest in quitting, and access to a computer with internet. One hundred thirty
eight subjects enrolled, and 134 completed the study. INTERVENTION: Positively
Smoke Free on the Web (PSFW), an 8-session, 7-week targeted tobacco treatment
program for PLWH, was compared with standard care (brief advice to quit and self
help brochure). All subjects were offered nicotine patches. MAIN OUTCOME
MEASURES: The main feasibility outcomes were number of sessions logged into,
number of Web pages visited, number of interactive clicks, and total time logged
in. The main efficacy outcome was biochemically verified, 7-day point prevalence
abstinence 3 months after intervention. RESULTS: PSFW subjects logged into a mean
of 5.5 of 8 sessions and 26.2 of 41 pages. They executed a mean of 10 interactive
clicks during a mean total of 59.8 minutes logged in. Most required reminder
phone calls to complete the sessions. Educational level, anxiety score, and home
access of the Web site were associated with Web site usage. Ten percent of the
PSFW group vs. 4.3% of controls achieved the abstinence end point. Among those
who completed all 8 sessions, 17.9% were abstinent, and among women completers,
30.8% were abstinent. CONCLUSIONS: Web-based treatment is a feasible strategy for
PLWH smokers, and preliminary findings suggest therapeutic efficacy.
PMID- 25118796
TI - Preventing tuberculosis among HIV-infected pregnant women in Lesotho: the case
for rolling out active case finding and isoniazid preventive therapy.
AB - BACKGROUND: The Lesotho Ministry of Health issued guidelines on active case
finding (ACF) for tuberculosis (TB) and isoniazid preventive therapy (IPT) in
April 2011. ACF has been recommended in maternal and child health (MCH) settings
globally, however, the feasibility of implementing IPT within MCH in countries
with high concurrent HIV and TB epidemics is unknown. DESIGN/METHODS: The study
evaluated the implementation of ACF and IPT guidelines in MCH settings in 2
health facilities in Lesotho. This descriptive prospective study analyzed data
collected during routine services. Categorical data and continuous variables were
summarized using descriptive statistics. The chi test or Wilcoxon rank-sum test
was used to ascertain significant associations between categorical and continuous
variables, respectively. RESULTS: Data from 160 HIV-positive and 640 HIV-negative
women were reviewed. Within this study population, 99.8% of women were screened
for TB, and 11.4% HIV-positive women compared with 2.3% HIV-negative women were
reported to have symptoms of TB (P < 0.001). IPT was initiated in 124/158 (78.5%)
HIV-positive pregnant women, 64.5% women completed a 6-month IPT regimen, 2
(1.6%) died of causes unrelated to IPT/TB, and 31.5% were lost to follow-up.
Predictors of IPT initiation among HIV-positive women included gestational age at
the first antenatal visit (unadjusted odds ratio, -0.93; 95% confidence interval:
-0.88 to 0.98), and receipt of antiretroviral therapy for treatment rather than
for prevention of mother-to-child transmission prophylaxis only (odds ratio,
4.59; 95% confidence interval: 1.32 to 15.93). CONCLUSIONS: Implementation of ACF
and IPT is feasible within the MCH setting. Uptake of IPT during pregnancy among
HIV-positive women was high, but with a high rate of loss to follow-up.
PMID- 25118797
TI - Metabotropic glutamate receptor 5 as a potential therapeutic target in
Huntington's disease.
AB - INTRODUCTION: Huntington's disease (HD) is an autosomal dominant
neurodegenerative disorder caused by a polyglutamine expansion in the amino
terminal region of the huntingtin (htt) protein, which underlies the loss of
striatal and cortical neurons. Glutamate has been implicated in a number of
neurodegenerative diseases, and several studies suggest that the metabotropic
glutamate receptor 5 (mGluR5) may represent a target for the treatment of HD.
AREAS COVERED: The main goal of this review is to discuss the current data in the
literature regarding the role of mGluR5 in HD and evaluate the potential of
mGluR5 as a therapeutic target for the treatment of HD. mGluR5 is highly
expressed in the brain regions affected in HD and is involved in movement
control. Moreover, mGluR5 interacts with htt and mutated htt profoundly affects
mGluR5 signaling. However, mGluR5 stimulation can activate both neuroprotective
and neurotoxic signaling pathways, depending on the context of activation. EXPERT
OPINION: Although the data published so far strongly indicate that mGluR5 plays a
major role in HD-associated neurodegeneration, htt aggregation and motor
symptoms, it is not clear whether mGluR5 stimulation can diminish or intensify
neuronal cell loss and HD progression. Thus, future experiments will be necessary
to further investigate the outcome of drugs acting on mGluR5 for the treatment of
neurodegenerative diseases.
PMID- 25118795
TI - High medication adherence during periconception periods among HIV-1-uninfected
women participating in a clinical trial of antiretroviral pre-exposure
prophylaxis.
AB - INTRODUCTION: Pre-exposure prophylaxis (PrEP) may be an important safer
conception strategy for HIV-1-uninfected women with HIV-1-infected partners.
Understanding medication adherence in this population may inform whether PrEP is
a feasible safer conception strategy. METHODS: We evaluated predictors of
pregnancy and adherence to study medication among HIV-1-uninfected women enrolled
in a randomized placebo-controlled trial of PrEP among African HIV-1
serodiscordant couples. Participants were counseled on HIV-1 risk reduction,
contraception, and adherence and tested for pregnancy at monthly study visits.
Pill counts of dispensed drug were performed and, at a subset of visits, plasma
was collected to measure active drug concentration. RESULTS: Among 1785 women,
pregnancy incidence was 10.2 per 100 person-years. Younger age, not using
contraception, having an additional sexual partner, and reporting unprotected sex
were associated with increased likelihood of pregnancy. Monthly clinic pill
counts estimated that women experiencing pregnancy took 97% of prescribed doses
overall, with at least 80% pill adherence for 98% of study months, and no
difference in adherence in the periconception period compared with previous
periods (P = 0.98). Tenofovir was detected in plasma at 71% of visits where
pregnancy was discovered. By multiple measures, adherence was similar for women
experiencing and not experiencing pregnancy (P >= 0.1). CONCLUSIONS: In this
clinical trial of PrEP, pregnancy incidence was 10% per year despite excellent
access to effective contraception. Women experiencing pregnancy had high
medication adherence, suggesting that PrEP may be an acceptable and feasible
safer conception strategy for HIV-1-uninfected women with HIV-1-serodiscordant
partners.
PMID- 25118799
TI - Two new drugs for skin and skin structure infections.
PMID- 25118800
TI - Sucroferric oxyhydroxide (Velphoro) for hyperphosphatemia.
PMID- 25118798
TI - Effects of high mobility group protein box 1 and toll like receptor 4 pathway on
warts caused by human papillomavirus.
AB - Accumulative evidence has demonstrated that inflammation has an important role in
human papillomavirus (HPV) oncogenicity. However, the effects of high mobility
group protein box 1 (HMGB1)-toll like receptor 4 (TLR4) signaling pathway
associated inflammation on epidermal warts caused by HPV remain unclear. The
present study investigated the HMGB1, TLR4 and nuclear factor-kappaB p65
expression in condyloma acuminatum (CA) and verruca vulgaris (VV).
Immunohistochemistry and western blot analysis revealed that p65 expression in
epithelial nuclei in VV and CA was significantly higher than in normal skin (NS)
(P<0.01), and p65 in CA was higher than in VV but this difference was not
significant. The level of extracellular HMGB1 increased significantly and
progressively from NS to VV to CA (P<0.05). The level of TLR4 on the surface of
epithelial membranes in the CA samples was significantly higher than in NS
(P<0.01), and TLR4 in VV samples was significantly lower than in NS (P<0.01).
There was a positive correlation between p65 expression in the epithelial nuclei
and HMGB1 in the epithelial intercellular spaces (r=0.5199, P<0.01). These
findings indicate that inflammation is intensified in warts caused by HPV. HMGB1
TLR4 pathway-associated inflammation may therefore have a pivotal role in CA.
HMGB1, rather than TLR4, may be a vital mediator of inflammation in VV. Therapies
targeting HMGB1 may be a potential strategy for the treatment of HPV-associated
warts.
PMID- 25118801
TI - Glycerol phenylbutyrate (Ravicti) for urea cycle disorders.
PMID- 25118802
TI - A transcutaneous electrical nerve stimulation device (Cefaly) for migraine
prevention.
PMID- 25118803
TI - Accumulated knowledge and prevention practices in oral health.
AB - This text begins by reflecting on health promotion and equity/ inequity. In
health, inequity is understood as a political concept that has moral implications
and that is committed to social justice. A discussion follows on some issues
regarding the risk and prevention of diseases, still considered a hegemonic
practice, and lack of experience in oral health-care, bearing in mind the concept
of vulnerability. The risk is probabilistic and involves the mathematical chances
of acquiring a disease in a certain group, whereas vulnerability addresses the
potential of acquiring or not acquiring a disease in a certain environment. The
need for systematic studies on determinants is stressed, with the ultimate goal
of improving health and reducing inequities, and with the concern and political
intention of including health equity in governmental policies.
PMID- 25118804
TI - Presence of a plant-like proton-translocating pyrophosphatase in a scuticociliate
parasite and its role as a possible drug target.
AB - The proton-translocating inorganic pyrophosphatases (H(+)-PPases) are primary
electrogenic H(+) pumps that derive energy from the hydrolysis of inorganic
pyrophosphate (PPi). They are widely distributed among most land plants and have
also been found in several species of protozoan parasites. Here we describe, for
the first time, the molecular cloning and functional characterization of a gene
encoding an H(+)-pyrophosphatase in the protozoan scuticociliate parasite
Philasterides dicentrarchi, which infects turbot. The predicted P. dicentrarchi
PPase (PdPPase) consists of 587 amino acids of molecular mass 61.7 kDa and an
isoelectric point of 5.0. Several motifs characteristic of plant vacuolar H(+)
PPases (V-H(+)-PPases) were also found in the PdPPase, which contains all the
sequence motifs of the prototypical type I V-H(+)-PPase from Arabidopsis thaliana
vacuolar pyrophosphatase type I (AVP1) plant. The PdPPase has a characteristic
residue that determines strict K(+)-dependence, but unlike AVP1, PdPPase contains
an N-terminal signal peptide (SP) sequence. Antibodies generated by vaccination
of mice with a genetic or recombinant protein containing a partial sequence of
the PdPPase and a common motif with the polyclonal antibody PABHK specific to
AVP1 recognized a single band of about 62 kDa in western blots. These antibodies
specifically stained both vacuole and the alveolar membranes of trophozoites of
P. dicentrarchi. H+ transport was partially inhibited by the bisphosphonate
pamidronate (PAM) and completely inhibited by NaF. The bisphosphonate PAM
inhibited both H+-translocation and gene expression. PdPPase and PAM also
inhibited in vitro growth of the ciliates. The apparent lack of V-H(+)-PPases in
vertebrates and the parasite sensitivity to PPI analogues may provide a molecular
target for developing new drugs to control scuticociliatosis.
PMID- 25118805
TI - Wind farm facilities in Germany kill noctule bats from near and far.
AB - Over recent years, it became widely accepted that alternative, renewable energy
may come at some risk for wildlife, for example, when wind turbines cause large
numbers of bat fatalities. To better assess likely populations effects of wind
turbine related wildlife fatalities, we studied the geographical origin of the
most common bat species found dead below German wind turbines, the noctule bat
(Nyctalus noctula). We measured stable isotope ratios of non-exchangeable
hydrogen in fur keratin to separate migrants from local individuals, used a
linear mixed-effects model to identify temporal, spatial and biological factors
explaining the variance in measured stable isotope ratios and determined the
geographical breeding provenance of killed migrants using isoscape origin models.
We found that 72% of noctule bat casualties (n = 136) were of local origin, while
28% were long-distance migrants. These findings highlight that bat fatalities at
German wind turbines may affect both local and distant populations. Our results
indicated a sex and age-specific vulnerability of bats towards lethal accidents
at turbines, i.e. a relatively high proportion of killed females were recorded
among migratory individuals, whereas more juveniles than adults were recorded
among killed bats of local origin. Migratory noctule bats were found to originate
from distant populations in the Northeastern parts of Europe. The large catchment
areas of German wind turbines and high vulnerability of female and juvenile
noctule bats call for immediate action to reduce the negative cross-boundary
effects of bat fatalities at wind turbines on local and distant populations.
Further, our study highlights the importance of implementing effective mitigation
measures and developing species and scale-specific conservation approaches on
both national and international levels to protect source populations of bats. The
efficacy of local compensatory measures appears doubtful, at least for migrant
noctule bats, considering the large geographical catchment areas of German wind
turbines for this species.
PMID- 25118807
TI - Profile of microRNAs associated with aging in rat liver.
AB - Recent studies suggest that small non-coding microRNAs (miRNAs or miRs) play an
important role in the regulation of genes involved in various cellular and
developmental processes. However, the expression of miRNAs during the aging
process remains largely unknown. The aim of the present study was to analyze
miRNA expression profiles in rat livers during the aging process. The livers of
male Wistar rats at different stages of development (fetal, aged 3 days, and 1,
2, 4, 8 and 36 weeks of age) were used. Total RNA was extracted from the livers.
We analyzed the expression levels of 679 rat miRNA probes. In addition,
immunohistochemical staining for proliferating cell nuclear antigen (PCNA) was
performed. Several up- and downregulated miRNAs were identified in the rat livers
at 7 different fetal developmental stages and at 36 weeks of age. We observed the
upregulation of miR-29a, miR-29c, miR-195 and miR-497, whereas miR-301a, miR-148b
3p, miR-7a, miR-93, miR-106b, miR-185, miR-450a, miR-539 and miR-301b were
downregulated in the aging rat livers. The number of PCNA-positive hepatocytes
was decreased with age. In conclusion, our findings suggest that these up- and
downregulated miRNAs play an important role in aging by regulating cell cycles
that are involved in liver senescence. Further investigation is required to
reveal additional target genes of the miRNAs expressed in the liver and the roles
of miRNAs in the developmental process of aging in the liver.
PMID- 25118808
TI - Unusual cyclic terpenoids with terminal pendant prenyl moieties: from occurrence
to synthesis.
AB - The paper reviews the known examples of cyclic terpenoids produced from open
chain polyenic precursors by an "unusual" biosynthetic pathway, involving
selective electrophilic attack on an internal double bond followed by
cyclization. The resulting compounds possess cyclic backbones with pendant
terminal prenyl groups. Synthetic approaches applied for the synthesis of such
specifically functionalized compounds are also discussed, as well as biological
activity of reported representatives.
PMID- 25118809
TI - Protuberant fibro-osseous lesions of the temporal bone: two additional case
reports.
AB - The most commonly encountered fibro-osseous lesions of the skull bone are fibrous
dysplasia and ossifying fibroma. Two cases of a unique "protuberant fibro-osseous
lesion of the temporal bone" were first described by Selesnick and colleagues in
1999, and 2 further cases were reported in 2010 under the name "Bullough lesion".
We recently found 2 new cases of this rare entity. Two Korean female patients
aged 70 and 54 years presented with slow growing postauricular masses without
pain or tenderness for 6 and 7 years, respectively. Computed tomography revealed
a 2.9 cm calcified mass in the temporal bone of the first patient, and a 5.5 cm
enhancing mass with internal cartilaginous matrix in the temporal bone of the
second patient. Intramedullary or intracranial extension was not found in either
case, and en bloc removals were performed. Microscopically, multiple round to
oval osseous islands were scattered throughout the bland fibrous stroma in both
cases. The osseous islands varied in size and were lamellar or woven, without
osteoblastic rimming, and surrounded by fibroblastic bands. Neither patient has
shown evidence of postoperative recurrence for 18 months. The location,
histology, and clinical course of these 2 cases were identical to the 4 cases
previously reported, although age and sex varied. The lesions were tested for the
R201H mutation in the GNAS gene, which is present in fibrous dysplasia. No
mutations were found, suggesting a different genetic background for these
lesions.
PMID- 25118806
TI - The potential of transcription factor-based genetic engineering in improving crop
tolerance to drought.
AB - Drought is one of the major constraints in crop production and has an effect on a
global scale. In order to improve crop production, it is necessary to understand
how plants respond to stress. A good understanding of regulatory mechanisms
involved in plant responses during drought will enable researchers to explore and
manipulate key regulatory points in order to enhance stress tolerance in crops.
Transcription factors (TFs) have played an important role in crop improvement
from the dawn of agriculture. TFs are therefore good candidates for genetic
engineering to improve crop tolerance to drought because of their role as master
regulators of clusters of genes. Many families of TFs, such as CCAAT,
homeodomain, bHLH, NAC, AP2/ERF, bZIP, and WRKY have members that may have the
potential to be tools for improving crop tolerance to drought. In this review,
the roles of TFs as tools to improve drought tolerance in crops are discussed.
The review also focuses on current strategies in the use of TFs, with emphasis on
several major TF families in improving drought tolerance of major crops. Finally,
many promising transgenic lines that may have improved drought responses have
been poorly characterized and consequently their usefulness in the field is
uncertain. New advances in high-throughput phenotyping, both greenhouse and field
based, should facilitate improved phenomics of transgenic lines. Systems biology
approaches should then define the underlying changes that result in higher yields
under water stress conditions. These new technologies should help show whether
manipulating TFs can have effects on yield under field conditions.
PMID- 25118810
TI - Activating BRAF V600E mutation in aggressive pediatric Langerhans cell
histiocytosis: demonstration by allele-specific PCR/direct sequencing and
immunohistochemistry.
AB - Langerhans cell histiocytosis (LCH) is a rare neoplastic disease originating from
cells characterized by antigen-presenting Langerhans cell phenotype. The clinical
spectrum of LCH is highly variable including localized and disseminated forms
mostly occurring in children. Recently, about 60% of LCHs were reported to carry
the activating BRAF mutation V600E. In our retrospective study, we evaluated the
occurrence and prognostic impact of the V600E mutation in formaldehyde-fixed,
paraffin-embedded samples from 15 pediatric LCH cases treated at our institution.
Allele-specific polymerase chain reaction (PCR) and direct sequencing were used
to demonstrate the presence of V600E mutation, and immunohistochemistry (IHC)
using the mutant protein-specific VE1 antibody clone was performed to confirm
mutant BRAF protein expression. Eight of 15 (53.3%) cases proved to be BRAF
mutants by any of the methods applied, with a single case showing a discrepancy
(PCR negative/IHC positive). Four of the BRAF-mutant cases (50.0%) showed
refractory disease and progressed to death within 43 months, whereas the
remaining mutant cases were stable and responded well to therapy. Wild-type BRAF
cases (7/15, 46.6%) with generally comparable initial presentation were all
treated successfully. In conclusion, activating V600E BRAF mutation can be
frequently demonstrated in pediatric LCH by both allele-specific PCR and IHC.
Unfavorable risk cases potentially also responding to BRAF-inhibitory therapy can
be identified by mutation testing using archival formaldehyde-fixed, paraffin
embedded tumor samples.
PMID- 25118811
TI - Uterine polyps with features overlapping with those of Mullerian adenosarcoma: a
clinicopathologic analysis of 29 cases emphasizing their likely benign nature.
AB - Mullerian adenosarcoma (MA) is a mixed Mullerian neoplasm composed of malignant
stroma and benign epithelium. Endometrial and endocervical polyps are common
entities in surgical pathology practice and most can be readily distinguished
from MA; however, some have overlapping features, causing diagnostic confusion.
In this study, we examined uterine polyps falling short of the diagnosis of MA
quantitatively, qualitatively, or both. Our aims were to (1) characterize
formally the morphologic features of atypical uterine polyps and (2) determine
clinical outcome. Cases were evaluated for morphologic features of MA (phyllodes
like architecture, intraglandular polypoid projections, altered periglandular
stroma, and stromal cytologic atypia), and the maximum number of mitoses per 10
high-power fields. The percentage involvement within a polyp by any atypical
feature was estimated. The most common change was abnormal architecture, although
periglandular stromal abnormalities and increased mitoses were also frequent
findings. Stromal cytologic atypia was rare and when present was focal and mild.
Histologic follow-up was performed in 24/29 (86%). Two patients had uterine
polyps with unusual features similar to those noted on the initial biopsy. The
remainder showed either polyp without unusual features or no residual polyp.
Clinical follow-up information was available for 28/29 (97%). Twenty-seven of 28
were alive without evidence of disease, whereas 1 patient had died of pancreatic
adenocarcinoma. We have shown that uterine polyps with features overlapping with
those of MA have a benign clinical course, even with conservative management, as
no cases showed progression or malignant transformation.
PMID- 25118812
TI - Distinguishing nested variants of urothelial carcinoma from benign mimickers by
TERT promoter mutation.
AB - Nested variant of urothelial carcinoma (NVUC) is an uncommon variant with
minimally atypical cytology, which may overlap with benign urothelial lesions
such as von Brunn nests, cystitis cystica, cystitis glandularis, and nephrogenic
adenoma. Because of the tumor's deceptively bland appearance, these cancers can
potentially be misdiagnosed as benign lesions, leading in some cases to a
significant delay in correct diagnosis and appropriate treatment. Prior studies
suggest that Ki67 and p53 are useful markers in distinguishing NVUC from benign
lesions. However, the overlap in the rates of immunoreactivity has prevented
pathologists from using these markers as reliable adjunct markers in
differentiating NVUC from mimickers. In addition, large nested variant urothelial
carcinoma (LNVUC), a relatively new entity, shares features of both the NVUC and
papillary urothelial carcinomas with an inverted growth pattern. They also mimic
benign lesions, such as proliferation of von Brunn nests and inverted urothelial
papilloma. With the recent demonstration of a strong association of TERT promoter
mutations and urothelial carcinoma, we hypothesized that TERT promoter mutations
would be a useful marker to distinguish NVUC and LNVUC from other benign
urothelial lesions. We have therefore sequenced the TERT promoter region of 20
cases of NVUC, 10 cases of LNVUC, 5 cases of von Brunn nests, 3 cases of cystitis
cystica, 3 cases of cystitis glandularis, and 3 cases of nephrogenic adenoma. We
found that 17 of 20 cases of NVUC and 8 of 10 cases of LNVUC had TERT promoter
mutation: C228T; no mutation was found in any of the benign mimickers (0/14).
This result strongly suggests that TERT promoter mutation is a useful adjunct
biomarker to distinguish NVUC and LNVUC from benign mimickers.
PMID- 25118813
TI - Gastrointestinal tract-derived pulse granulomata: clues to an underrecognized
pseudotumor.
AB - Pulse granulomata (PG) in the lung and oral pathology literature are presumed due
to food (pulse) introduced by mucosal injury. Herein, we report the largest
series of PG in the gastrointestinal tract (GIT): 22 resections were
prospectively collected from 17 patients (8 men, range=28 to 85 y). All patients
had a history of intestinal injury/disease: diverticulitis, fistula,
adenocarcinoma, perforation, ulcerative colitis, appendicitis, anastomotic site
leak, and/or stent leak. Nine of 22 specimens were designated "masses"; most of
these were clinically concerning for neoplasia. Sites of involvement included the
small and large intestine, appendix, liver, gallbladder, mesentery, omentum,
peritoneum, cervix, ovary, and skin. PG were typically nodular (21/22) and
multifocal (15/22); most involved the external surface of the bowel (20/22), and
they ranged in size from 1.5 to 100 mm. Histologically, they contained variable
amounts of hyaline ribbons and rings, inflammation, foreign body giant cells,
calcifications, and food; larger lesions displayed circumferential stellate
fibrosis (12/22). We describe 3 morphologic variants: hyaline predominant
(mimicking amyloid), cellular predominant (mimicking spindle cell neoplasms), and
sclerosing mesenteritis-like. All patients are alive and well at the time of
follow-up. Histologically processed legumes showed similar structures as those
identified in PG, providing support for an entrapped food origin. In summary, we
detail important clinicopathologic clues, describe the PG morphologic spectrum,
and demonstrate how to distinguish PG from their mimics. Although PG can present
as clinically concerning masses, we conclude that they are pseudotumors arising
secondary to entrapped food introduced through mucosal trauma, similar to their
lung and oral counterparts.
PMID- 25118814
TI - Annexin A10 expression in microsatellite-unstable colorectal cancers: is it
specific to sporadic tumors?
PMID- 25118815
TI - Lobular panniculitic infiltrates with overlapping histopathologic features of
lupus panniculitis (lupus profundus) and subcutaneous T-cell lymphoma: a
conceptual and practical dilemma.
AB - Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is characterized by
panniculitic infiltrates that may be difficult to distinguish from inflammatory
disorders, particularly lupus erythematosus profundus (LEP). We report on 11
patients (M:F=5:6; median age: 49 y; range: 20 to 75 y) presenting with lobular
panniculitic infiltrates showing histopathologic features of both SPTCL and LEP
in different parts of the same biopsy specimen. The areas showing aspects of
SPTCL revealed dense infiltrates of small and medium-sized, atypical alpha/beta T
cytotoxic lymphocytes with focal rimming of the adipocytes and high
proliferation. In other areas the infiltrate was composed of nodules of B
lymphocytes arranged characteristically at the periphery of the fat lobules and
in the septa and showing a low proliferation rate. CD123-positive plasmocytoid
dendritic cells arranged in small clusters could be observed in 3 cases. Our
observation raises an important question concerning the relationship between
SPTCL and LEP. A simple chance overlap of 2 unrelated pathologies seems unlikely,
as we could observe these unusual features in 11 cases, much more than mere
chance would justify. Three other hypotheses may explain the features observed in
our patients: (1) these are examples of SPTCL with focal histologic features
mimicking those of LEP; (2) these are examples of LEP with focal atypical
histologic features mimicking those of SPTCL; (3) SPTCL and LEP may represent 2
ends of a spectrum, a hypothesis that may be supported by the frequent
association of the 2 diseases.
PMID- 25118817
TI - Light sheet fluorescence microscopy (LSFM): past, present and future.
AB - Light sheet fluorescence microscopy (LSFM) has emerged as an important imaging
modality to follow biology in live 3D samples over time with reduced
phototoxicity and photobleaching. In particular, LSFM has been instrumental in
revealing the detail of early embryonic development of Zebrafish, Drosophila, and
C. elegans. Open access projects, DIY-SPIM, OpenSPIM, and OpenSPIN, now allow
LSFM to be set-up easily and at low cost. The aim of this paper is to facilitate
the set-up and use of LSFM by reviewing and comparing open access projects, image
processing tools and future challenges.
PMID- 25118816
TI - Intracellular TCR-signaling pathway: novel markers for lymphoma diagnosis and
potential therapeutic targets.
AB - Despite the immunologic functions of T-cell receptor signaling molecules being
extensively investigated, their potential as immunohistochemical markers has been
poorly explored. With this background, we evaluated the expression of 5
intracellular proteins-GADS, DOK2, SKAP55, ITK, and PKCalpha-involved in T-cell
receptor signaling in normal and neoplastic hematologic tissue samples, using
antibodies raised against fixation-resistant epitopes of the 5 molecules. All 5
antibodies were associated with normal T-cell differentiation. GADS, DOK2,
SKAP55, and ITK turned out to be T-cell lineage-specific markers in the setting
of lymphoid and myeloid precursor neoplasms but showed differential expression in
peripheral T-cell lymphoma (PTCL) subtypes, being detected in PTCL/not otherwise
specified (NOS) and angioimmunoblastic T-cell lymphoma but negative in anaplastic
large cell lymphoma (ALCL). Peripheral B-cell lymphomas were consistently
negative for ITK, with occasional cases showing expression of DOK2 and SKAP55,
and a proportion (47%) of hairy cell leukemias were GADS. Notably, PKCalpha
highlighted a defective antigen in both PTCL/NOS (6%) and angioimmunoblastic T
cell lymphoma (10%), mostly negative in ALCL, and was aberrantly expressed in
classical Hodgkin lymphoma (65%), Burkitt lymphoma (48%), and plasma cell myeloma
(48%). In conclusion, all five molecules evaluated play a role in T-cell
differentiation in normal and neoplastic tissues. They can be applied confidently
to routine sections contributing primarily to assignment of T-lineage
differentiation in the setting of hematopoietic precursor neoplasms
(GADS/DOK2/SKAP55/ITK) and for the differential diagnosis between ALCL and
PTCL/NOS (GADS/DOK2/SKAP55/ITK) or classical Hodgkin lymphoma (PKCalpha).
Finally, association with specific tumor subtypes may have therapeutic potential.
PMID- 25118818
TI - Controlled drug release from the aggregation-disaggregation behavior of pH
responsive microgels.
AB - In this submission, two independent sets of microgels were synthesized that
exhibit pH responsivity over different solution pH ranges. The microgels were
synthesized by copolymerizing two different comonomers with poly(N
isopropylacrylamide) (pNIPAm). The microgels copolymerized with acrylic acid
exhibit a negative charge above pH 4.25, while the microgels copolymerized with N
[3-(dimethylamino)propyl]methacrylamide exhibit a positive charge below pH 8.4;
these microgels are neutral outside of these pH ranges. We show that aggregates
form when the two independent sets of microgels are exposed to one another in a
solution that renders them both charged. Furthermore, in solutions of pH outside
of this range, the microgels disaggregate because one of the microgels becomes
neutralized. This behavior was exploited to load (aggregation) and release
(disaggregation) a small-molecule model drug, methylene blue. This aggregate
based system is one example of how pNIPAm-based microgels can be used for
controlled/triggered drug delivery, which can have implications for therapeutics.
PMID- 25118820
TI - Crystal structure and luminescence property of a novel blue-emitting
Cs2xCa2xGd2(1-x)(PO4)2:Eu(2+) (x = 0.36) phosphor.
AB - A novel blue-emitting double-phosphate phosphor Cs0.72Ca0.72Gd1.28(PO4)2:Eu(2+)
was synthesized by the sol-gel method, and the structure and luminescence
properties were investigated in detail. The crystal structure and chemical
composition of Cs0.72Ca0.72Gd1.28(PO4)2 matrix was analyzed and determined based
on Rietveld refinements and phase and chemical composition analysis. The
composition-optimized Cs0.72Ca0.72Gd1.28(PO4)2:Eu(2+) exhibited strong blue
light, peaking at 462 nm upon excitation at 365 nm with the CIE coordinates of
(0.139, 0.091). The quenching concentration of Eu(2+) in the
Cs0.72Ca0.72Gd1.28(PO4)2 phase was about 0.01 and attributed to the dipole
quadrupole interaction. The thermally stable luminescence properties,
fluorescence decay curves and diffuse reflectance spectra of
Cs0.72Ca0.72Gd1.28(PO4)2:Eu(2+) phosphors are also discussed, all of which
indicate that the Cs0.72Ca0.72Gd1.28(PO4)2:Eu(2+) phosphor is a promising
phosphor for application in white-light UV LEDs.
PMID- 25118819
TI - Quantitative comparison and metabolite profiling of saponins in different parts
of the root of Panax notoginseng.
AB - Although both rhizome and root of Panax notoginseng are officially utilized as
notoginseng in "Chinese Pharmacopoeia", individual parts of the root were
differently used in practice. To provide chemical evidence for the differentiated
usage, quantitative comparison and metabolite profiling of different portions
derived from the whole root, as well as commercial samples, were carried out,
showing an overall higher content of saponins in rhizome, followed by main root,
branch root, and fibrous root. Ginsenoside Rb2 was proposed as a potential marker
with a content of 0.5 mg/g as a threshold value for differentiating rhizome from
other parts. Multivariate analysis of the metabolite profile further suggested 32
saponins as potential markers for the discrimination of different parts of
notoginseng. Collectively, the study provided comprehensive chemical evidence for
the distinct usage of different parts of notoginseng and, hence, is of great
importance for the rational application and exploitation of individual parts of
notoginseng.
PMID- 25118821
TI - Oxidative dehydrogenation of ethane on dynamically rearranging supported chloride
catalysts.
AB - Ethane is oxidatively dehydrogenated with a selectivity up to 95% on catalysts
comprising a mixed molten alkali chloride supported on a mildly redox-active
Dy2O3-doped MgO. The reactive oxyanionic OCl(-) species acting as active sites
are catalytically formed by oxidation of Cl(-) at the MgO surface. Under reaction
conditions this site is regenerated by O2, dissolving first in the alkali
chloride melt, and in the second step dissociating and replenishing the oxygen
vacancies on MgO. The oxyanion reactively dehydrogenates ethane at the melt-gas
phase interface with nearly ideal selectivity. Thus, the reaction is concluded to
proceed via two coupled steps following a Mars-van-Krevelen-mechanism at the
solid-liquid and gas-liquid interface. The dissociation of O2 and/or the
oxidation of Cl(-) at the melt-solid interface is concluded to have the lowest
forward rate constants. The compositions of the oxide core and the molten
chloride shell control the catalytic activity via the redox potential of the
metal oxide and of the OCl(-). Traces of water may be present in the molten
chloride under reaction conditions, but the specific impact of this water is not
obvious at present. The spatial separation of oxygen and ethane activation sites
and the dynamic rearrangement of the surface anions and cations, preventing the
exposure of coordinatively unsaturated cations, are concluded to be the origin of
the surprisingly high olefin selectivity.
PMID- 25118823
TI - Narrative review of the barriers and facilitators to chlamydia testing in general
practice.
AB - As the cornerstone of Australian primary health care, general practice is a
setting well suited for regular chlamydia testing but testing rates remain low.
This review examines the barriers and facilitators to chlamydia testing in
general practice. Six databases--Medline, PubMed, Meditext, PsycInfo, Scopus and
Web of Science--were used to identify peer-reviewed publications that addressed
barriers and facilitators to chlamydia testing in general practice using the
following terms: 'chlamydia test*', 'STI test*' 'general practice', 'primary
care', 'family medicine', 'barriers', 'facilitators' and 'enablers' from 1997
until November 2013. Data about the study design and key findings were extracted
from the publications. A framework method was used to manage the data and
organise publications into three categories -patient, general practitioner, and
general practice. Key findings were then classified as a barrier or facilitator.
Sixty-nine publications were included, with 41 quantitative studies, 17
qualitative studies, and 11 using mixed methods. Common barriers identified in
all three groups included a lack of knowledge, awareness or training, demands on
time and workload, and the social context of testing. Facilitators included the
normalisation of testing, the use of nurses and other practice staff, education
and incentives. Numerous barriers and facilitators to chlamydia testing in
general practice have been identified. While the barriers are well studied, many
of the facilitators are not as well researched, and highlight areas for further
study.
PMID- 25118822
TI - Generation of Ugt1-deficient murine liver cell lines using TALEN technology.
AB - The Crigler-Najjar Syndrome Type I (CNSI) is a rare genetic disorder caused by
mutations in the Ugt1a1 gene. It is characterized by unconjugated
hyperbilirubinemia that may result in severe neurologic damage and death if
untreated. To date, liver transplantation is the only curative treatment. With
the aim of generating mutant cell lines of the Ugt1 gene, we utilized the TALEN
technology to introduce site-specific mutations in Ugt1 exon 4. We report a fast
and efficient method to perform gene knockout in tissue culture cells, based on
the use of TALEN pairs targeting restriction enzyme (RE) sites in the region of
interest. This strategy overcame the presence of allele-specific single
nucleotide polymorphisms (SNPs) and pseudogenes, conditions that limit INDELs'
detection by Surveyor. We obtained liver-derived murine N-Muli cell clones having
INDELs with efficiency close to 40%, depending on the TALEN pair and RE target
site. Sequencing of the target locus and WB analysis of the isolated cell clones
showed a high proportion of biallelic mutations in cells treated with the most
efficient TALEN pair. Ugt glucuronidation activity was reduced basal levels in
the biallelic mutant clones. These mutant liver-derived cell lines could be a
very useful tool to study biochemical aspects of Ugt1 enzyme activity in a more
natural context, such as substrate specificity, requirement of specific co
factors, the study of inhibitors and other pharmacological aspects, and to
correlate enzyme activity to the presence of specific mutations in the gene, by
adding back to the mutant cell clones specific variants of the Ugt1 gene. In
addition, since genome editing has recently emerged as a potential therapeutic
approach to cure genetic diseases, the definition of the most efficient TALEN
pair could be an important step towards setting up a platform to perform genome
editing in CNSI.
PMID- 25118824
TI - Influence of functional groups on organic aerosol cloud condensation nucleus
activity.
AB - Organic aerosols in the atmosphere are composed of a wide variety of species,
reflecting the multitude of sources and growth processes of these particles.
Especially challenging is predicting how these particles act as cloud
condensation nuclei (CCN). Previous studies have characterized the CCN efficiency
for organic compounds in terms of a hygroscopicity parameter, kappa. Here we
extend these studies by systematically testing the influence of the number and
location of molecular functional groups on the hygroscopicity of organic
aerosols. Organic compounds synthesized via gas-phase and liquid-phase reactions
were characterized by high-performance liquid chromatography coupled with
scanning flow CCN analysis and thermal desorption particle beam mass
spectrometry. These experiments quantified changes in kappa with the addition of
one or more functional groups to otherwise similar molecules. The increase in
kappa per group decreased in the following order: hydroxyl ? carboxyl >
hydroperoxide > nitrate ? methylene (where nitrate and methylene produced
negative effects, and hydroperoxide and nitrate groups produced the smallest
absolute effects). Our results contribute to a mechanistic understanding of
chemical aging and will help guide input and parametrization choices in models
relying on simplified treatments such as the atomic oxygen:carbon ratio to
predict the evolution of organic aerosol hygroscopicity.
PMID- 25118825
TI - Vapor-wall deposition in chambers: theoretical considerations.
AB - In order to constrain the effects of vapor-wall deposition on measured secondary
organic aerosol (SOA) yields in laboratory chambers, researchers recently varied
the seed aerosol surface area in toluene oxidation and observed a clear increase
in the SOA yield with increasing seed surface area (Zhang, X.; et al. Proc. Natl.
Acad. Sci. U.S.A. 2014, 111, 5802). Using a coupled vapor-particle dynamics
model, we examine the extent to which this increase is the result of vapor-wall
deposition versus kinetic limitations arising from imperfect accommodation of
organic species into the particle phase. We show that a seed surface area
dependence of the SOA yield is present only when condensation of vapors onto
particles is kinetically limited. The existence of kinetic limitation can be
predicted by comparing the characteristic time scales of gas-phase reaction,
vapor-wall deposition, and gas-particle equilibration. The gas-particle
equilibration time scale depends on the gas-particle accommodation coefficient
alphap. Regardless of the extent of kinetic limitation, vapor-wall deposition
depresses the SOA yield from that in its absence since vapor molecules that might
otherwise condense on particles deposit on the walls. To accurately extrapolate
chamber-derived yields to atmospheric conditions, both vapor-wall deposition and
kinetic limitations must be taken into account.
PMID- 25118827
TI - Evaluation of visual acuity, macular status, and subfoveal choroidal thickness
changes after cataract surgery in eyes with diabetic retinopathy.
AB - PURPOSE: Progression of diabetic macular edema has been reported as a common
cause of poor visual acuity recovery after cataract surgery in patients with
diabetes. Despite being responsible for the blood supply to the outer retina, the
role of the choroidal layer in the pathogenesis of diabetic retinopathy (DR) is
not yet understood. Our objective is to characterize macular and subfoveal
choroidal thickness changes after cataract surgery in eyes with DR. METHODS:
Thirty-five eyes with clinically significant cataract of patients with DR were
divided into three groups based on clinical and optical coherence tomography
findings: patients with DR without macular edema, patients with DR and macular
thickening detected on optical coherence tomography, and finally patients with
clinically significant macular edema. All cases were submitted to ophthalmologic
examination and spectral domain optical coherence tomography 1 week before
cataract surgery and repeated 1 month after surgery. Patients with preoperative
clinically significant macular edema were treated with intravitreal bevacizumab
at the time of surgery. RESULTS: All groups showed a significant increase in
visual acuity 1 month after surgery (P < 0.001). Mean foveal thickness increased
significantly in all groups, including controls (P = 0.013), except in patients
who were simultaneously treated with intravitreal bevacizumab (P = 0.933). An
increase of maximum macular thickness of at least 11% was found in 25.7% of the
DR eyes, but no such increase occurred in the control eyes. No significant change
was verified for subfoveal choroidal thickness in any of the studied groups.
CONCLUSION: Surgical inflammation associated with cataract surgery caused a
significant increase of macular thickness in control and DR eyes that were not
treated with intravitreous bevacizumab. Such macular changes were not accompanied
by subfoveal choroidal thickness changes in any of the study groups, suggesting
that the changes in macular thickness associated with the surgery are not related
to changes in choroidal thickness and that there is no relation between inner
blood-retinal barrier status and diabetic choroidal angiopathy.
PMID- 25118826
TI - Polysialylated N-glycans identified in human serum through combined developments
in sample preparation, separations, and electrospray ionization-mass
spectrometry.
AB - The N-glycan diversity of human serum glycoproteins, i.e., the human blood serum
N-glycome, is both complex and constrained by the range of glycan structures
potentially synthesizable by human glycosylation enzymes. The known glycome,
however, has been further limited by methods of sample preparation, available
analytical platforms, e.g., based upon electrospray ionization-mass spectrometry
(ESI-MS), and software tools for data analysis. In this report several
improvements have been implemented in sample preparation and analysis to extend
ESI-MS glycan characterization and to include polysialylated N-glycans. Sample
preparation improvements included acidified, microwave-accelerated, PNGase F N
glycan release to promote lactonization, and sodium borohydride reduction, that
were both optimized to improve quantitative yields and conserve the number of
glycoforms detected. Two-stage desalting (during solid phase extraction and on
the analytical column) increased sensitivity by reducing analyte signal division
between multiple reducing-end-forms or cation adducts. Online separations were
improved by using extended length graphitized carbon columns and adding TFA as an
acid modifier to a formic acid/reversed phase gradient, providing additional
resolving power and significantly improved desorption of both large and heavily
sialylated glycans. To improve MS sensitivity and provide gentler ionization
conditions at the source-MS interface, subambient pressure ionization with
nanoelectrospray (SPIN) was utilized. When these improved methods are combined
together with the Glycomics Quintavariate Informed Quantification (GlyQ-IQ)
recently described (Kronewitter et al. Anal. Chem. 2014, 86, 6268-6276), we are
able to significantly extend glycan detection sensitivity and provide expanded
glycan coverage. We demonstrated the application of these advances in the context
of the human serum glycome, and for which our initial observations included the
detection of a new class of heavily sialylated N-glycans, including
polysialylated N-glycans.
PMID- 25118828
TI - Fractional anisotropy in corpus callosum is associated with facilitation of motor
representation during ipsilateral hand movements.
AB - BACKGROUND: Coactivation of primary motor cortex ipsilateral to a unilateral
movement (M1(ipsilateral)) has been observed, and the magnitude of activation is
influenced by the contracting muscles. It has been suggested that the
microstructural integrity of the callosal motor fibers (CMFs) connecting M1
regions may reflect the observed response. However, the association between the
structural connectivity of CMFs and functional changes in M1(ipsilateral) remains
unclear. The purpose of this study was to investigate the relationship between
functional changes within M1(ipsilateral) during unilateral arm or leg movements
and the microstructure of the CMFs connecting both homotopic representations (arm
or leg). METHODS: Transcranial magnetic stimulation was used to assess changes in
motor evoked potentials (MEP) in an arm muscle during unilateral movements
compared to rest in fifteen healthy adults. Functional magnetic resonance imaging
was then used to identify regions of M1 associated with either arm or leg
movements. Diffusion-weighted imaging data was acquired to generate CMFs for arm
and leg areas using the areas of activation from the functional imaging as seed
masks. Individual values of regional fractional anisotropy (FA) of arm and leg
CMFs was then calculated by examining the overlap between CMFs and a standard
atlas of corpus callosum. RESULTS: The change in the MEP was significantly larger
in the arm movement compared to the leg movement. Additionally, regression
analysis revealed that FA in the arm CMFs was positively correlated with the
change in MEP during arm movement, whereas a negative correlation was observed
during the leg movement. However, there was no significant relationship between
FA in the leg CMF and the change in MEP during the movements. CONCLUSIONS: These
findings suggest that individual differences in interhemispheric structural
connectivity may be used to explain a homologous muscle-dominant effect within
M1(ipsilateral) hand representation during unilateral movement with topographical
specificity.
PMID- 25118830
TI - Room-temperature near-infrared high-Q perovskite whispering-gallery planar
nanolasers.
AB - Near-infrared (NIR) solid-state micro/nanolasers are important building blocks
for true integration of optoelectronic circuitry. Although significant progress
has been made in III-V nanowire lasers with achieving NIR lasing at room
temperature, challenges remain including low quantum efficiencies and high Auger
losses. Importantly, the obstacles toward integrating one-dimensional nanowires
on the planar ubiquitous Si platform need to be effectively tackled. Here we
demonstrate a new family of planar room-temperature NIR nanolasers based on
organic-inorganic perovskite CH3NH3PbI(3-a)X(a) (X = I, Br, Cl) nanoplatelets.
Their large exciton binding energies, long diffusion lengths, and naturally
formed high-quality planar whispering-gallery mode cavities ensure adequate gain
and efficient optical feedback for low-threshold optically pumped in-plane
lasing. We show that these remarkable wavelength tunable whispering-gallery
nanolasers can be easily integrated onto conductive platforms (Si, Au, indium tin
oxide, and so forth). Our findings open up a new class of wavelength tunable
planar nanomaterials potentially suitable for on-chip integration.
PMID- 25118829
TI - Cachexia: a problem of energetic inefficiency.
AB - An alteration of energy balance is the immediate cause of the so-called cachexia.
Although alterations of energy intake are often associated with cachexia, it has
lately became clear that an increased energy expenditure is the main cause of
wasting associated with different types of pathological conditions, such as
cancer, infections or chronic heart failure among others. Different types of
molecular mechanisms contribute to energy expenditure and, therefore, involuntary
body weight loss; among them, adenosine triphosphate (ATP) consumption by
sarcoplasmic reticulum Ca(2+) pumps could represent a key mechanism. In other
cases, an increase in energy inefficiency will further contribute to energy
imbalance.
PMID- 25118831
TI - High-level expression and characterization of bioactive human truncated variant
of hepatocyte growth factor in Escherichia coli.
AB - Hepatocyte growth factor (HGF) is an effective anti-fibrotic factor because of
its bioactivity in inhibiting fibrosis-related proteins in the development of
hepatic fibrosis. However, high-level production of bioactive mature form HGF is
difficult because of its complex structure. Here, we report a non-fusion protein
expression system to obtain truncated variant of N-terminal hairpin and first
kringle domains of HGF (tvNK1) in Escherichia coli to determine its anti-fibrotic
effects on hepatic stellate cells (HSCs). Under the selected conditions of
cultivation and isopropyl-beta-D-1-thiogalactopyranoside induction, the
expression level of tvNK1 accounted for approximately 65 % of the total cellular
protein and 50 % of fusion protein in the supernatant of whole cell lysates. The
recombinant protein could be purified in one step with Ni(2+)-affinity
chromatograph. Finally, about 65 mg recombinant tvNK1 was obtained from 1 l
fermentation culture with no <95 % purity. In vitro, the final purified tvNK1 was
shown to inhibit the proliferation of HSCs and decrease the mRNA and protein
expression levels of fibrosis-related COL1A1 and alpha-smooth muscle actin genes.
PMID- 25118832
TI - Celastrus paniculatus Willd. mitigates t-BHP induced oxidative and apoptotic
damage in C2C12 murine muscle cells.
AB - Identification, exploration and scientific validation of antioxidant rich herbal
extracts to mitigate the radical induced cell damage provide new insights in the
field of ayurvedic research/therapies. In the present study, we evaluated the
anti-oxidant and anti-apoptotic potential of Celastrus paniculatus seed extract
(CPSE) against tertiary butyl hydroperoxide (t-BHP) induced mice muscle cell
damage. The extract at a dose of 50 ug/ml protected the cells up to 70 % as
evidenced by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
cell survival assay and also prevented LDH leakage against t-BHP induced
cytotoxicity. CPSE showed potential antioxidant activity by restoring
mitochondrial membrane potential and inhibited reactive oxygen species generation
and lipid peroxidation. CPSE pretreatment also regulated the antioxidant markers
such as superoxide dismutase and catalase enzymes content and proteins
expression. Further CPSE showed anti-apoptotic effects by regulating cytochrome-C
and heat shock protein-70 expression and also showed 43 % muscle cell DNA damage
inhibitory activity against t-BHP challenge as observed by single cell gel
electrophoresis assay. Overall the extract inhibits the muscle cell damage, thus
explaining the possible anti-oxidant/anti-apoptotic defense status of the C.
paniculatus seed extract.
PMID- 25118833
TI - Vitamin A concentration in human milk and its relationship with liver reserve
formation and compliance with the recommended daily intake of vitamin A in pre
term and term infants in exclusive breastfeeding.
AB - PURPOSE: To evaluate vitamin A concentration in mature breast milk of nursing
mothers aiming to meet the daily needs and the formation of liver reserve in pre
term (PT) and term infants (T) in comparison with the recommended intake for this
nutrient in this group. METHODS: We analyzed the retinol concentration in the
milk of 120 nursing mothers (40 of PT infants and 80 of T infants) by collecting
10 mL of mature breast milk, held by a hand spray of one of the breasts 2 h after
the last feeding in the morning. The cutoff points adopted for identification of
vitamin A deficiency (VAD) and the liver reserve were <1.05 and >2.3 MUmol/L,
respectively. RESULTS: The concentrations of retinol in the human milk of T
infants were superior to concentrations in the milk of PT infants (1.87 + 0.81 >
1.38 + 0.67 MUmol/L, p < 0.0001). They were higher in T compared to PT (352.64 +
152.72 > 217.65 + 105.65 MUg, p < 0.0001), but both were below the
recommendation. VAD was 20.0 % (T) and 27.5 % (PT). Only 40.0 % (T) and 22.5 %
(PT) of the mothers had retinol concentrations in milk above 2.3 mmol/L.
CONCLUSION: The milk of the nursing mothers studied did not have enough retinol
to meet the daily needs and to form liver reserve in both groups, especially in
PT newborns. This finding reinforces the idea that supplementation with massive
doses of vitamin A in the immediate postpartum period can be used as a protective
device of the infant against VAD.
PMID- 25118834
TI - Sequential combination of flavopiridol with Taxol synergistically suppresses
human ovarian carcinoma growth.
AB - PURPOSE: The purpose is to investigate the effects of the sequential combination
treatment of Taxol and flavopiridol on human ovarian carcinoma in vitro and in
vivo. METHODS: Cell viabilities were determined using the cell counting kit and
by flow cytometry. RT-PCR, TUNEL, and immunoblotting assays were used to detect
cellular apoptotic activities following treatments. Tumor growth and microvessel
density (MVD) detection of mice bearing SKOV3 cells were studied. RESULTS: Taxol
or flavopiridol alone was cytotoxic against SKOV3 cells in vitro with a viability
rate of 38.2 +/- 1.3 % for 1 umol/L Taxol and 44.3 +/- 5.9 % for 300 nM
flavopiridol. Sequential combination treatment with Taxol and flavopiridol
resulted in a viability rate of 9.1 +/- 0.8 %. The apoptotic rate of SKOV3 cells
was 15.7 +/- 1.7, 9.4 +/- 0.4 and 51.1 +/- 2.5 % for Taxol, flavopiridol, and
combination of Taxol and flavopiridol, respectively. Significant synergisms were
observed in SKOV3 cells in vitro, following the sequential combination of Taxol
for 24 h followed by flavopiridol for 24 h, which resulted in the most
substantial cell death and the highest apoptotic rate. All treatments showed
significant suppression of tumor growth at the end point of the in vivo study.
All treatments significantly reduce the value of MVD. CONCLUSIONS: Sequential
combination treatment with Taxol and flavopiridol exerted synergistic cytotoxic
activities against SKOV3 cells in vitro and significantly suppress the tumor
growth of mice bearing SKOV3 cells. It should be further explored as a potential
clinically useful regimen against ovarian cancer.
PMID- 25118835
TI - The expression of GLTSCR2 in cervical intra-epithelial lesion and cancer.
AB - BACKGROUND: GLTSCR2 was originally identified as a candidate tumor suppressor in
several types of cancers. The present study was to investigate the expression
pattern of GLTSCR2 in different cervical lesion tissues, appraise its potential
role in cervical cancerogenesis. METHODS: 225 histologically confirmed samples
representing a wide range of cervical disease processes were studied in this
study using immunohistochemistry (IHC). RESULTS: Compared with normal cervix and
low-grade cervical intra-epithelial neoplasia (CIN I), cervical cancer and high
grade cervical intra-epithelial neoplasia (CIN II-III) tissues had lower
expression scores of IHC staining of GLTSCR2. The positive staining signals of
GLTSCR2 in CIN were decreased according to the grades of the intra-epithelial
lesions. The IHC scores of GLTSCR2 in cervical cancer tissues were significantly
lower than that in adjacent normal tissues. Different from previous report, we
also found that GLTSCR2 was expressed in both nucleus and cytoplasm of cervical
tissues, and the cytoplasmic expression of GLTSCR2 was observed in almost all
tissues. CONCLUSIONS: We demonstrated the GLTSCR2 expression decreased with the
rise of the grade of cervical lesions. GLTSCR2 may play an important role in
carcinogenesis of cervical cancer.
PMID- 25118836
TI - Efficacies and pregnant outcomes of fertility-sparing treatment with
medroxyprogesterone acetate for endometrioid adenocarcinoma and complex atypical
hyperplasia: our experience and a review of the literature.
AB - PURPOSE: We retrospectively analyzed oncologic and reproductive outcomes of
fertility-seeking premenopausal women with complex atypical hyperplasia (CAH) or
Grade 1 endometrial adenocarcinoma (G1EA) who underwent medical management with
high-dose medroxyprogesterone acetate (MPA) therapy. METHODS: Patients were given
a dose of 400-600 mg of MPA orally on a daily basis. They had histologically
confirmed CAH or G1EA at presumed stage IA and wished to preserve fertility.
Endometrial tissue sampling was carried out by dilation and curettage before and
after the treatment and the pathologic response to MPA treatment was assessed.
RESULTS: A total of 27 premenopausal patients received MPA therapy. The median
follow-up time was 39.2 months (3.4-153.8 months). Complete response was achieved
in 81.8 % (9/11) of CAH cases and 68.8 % (11/16) of G1EA. Although no recurrences
were found in CAH patients, nine G1EA patients (81.8 %) eventually recurred and
underwent total hysterectomy. Neither therapeutic death nor irreversible
toxicities were observed during the follow-up periods. Five patients (4 CAH and 1
G1EA) became pregnant and had nine live births. CONCLUSION: The high efficacy of
fertility-sparing treatment with MPA was shown demonstrated. MPA therapy can be
considered acceptable for the purpose of enabling patients to preserve their
fertility. However, the rate of recurrence was high in patients with G1EA. Even
in responders, close follow-up is required and a total hysterectomy needs to be
considered without delay. Patients should be aware of the risks and limitations
of this conservative treatment.
PMID- 25118837
TI - Glutathione S-transferase M1 modulates allergen-induced NF-kappaB activation in
asthmatic airway epithelium.
AB - BACKGROUND: Glutathione S-transferase M1 (GSTM1) is a phase II enzyme and
regulator of inflammatory signaling in airway epithelial cells. We have found
upregulation of neutrophilic airway inflammation in atopic asthmatics expressing
GSTM1 gene (GSTM1+) compared to GSTM1null asthmatics. We hypothesized that GSTM1
modulates NF-kappaB activation in bronchial epithelium in atopic asthmatics. We
determined regulation of allergen-induced NF-kappaB activation in bronchial
epithelium by GSTM1 in human atopic asthmatics in vivo. METHODS: Endobronchial
biopsies and bronchoalveolar lavage fluid samples were collected from 13 GSTM1+
and 12 GSTM1null human atopic asthmatics at baseline and 24 h after segmental
allergen challenge. A quantitative analysis of NF-kappaB activation in airway
epithelium was accomplished using a polyclonal antibody against the
phosphorylated p65 component of NF-kappaB. Elastase-positive neutrophils in the
bronchial wall were quantified. RESULTS: Postallergen neutrophilia in airway
subepithelium and epithelial lining fluid was greater in GSTM1+ compared to
GSTM1null asthmatics. Airway eosinophilia was similar in GSTM1+ and GSTM1null
asthmatics. Allergen-provoked NF-kappaB induction in bronchial epithelium was
significantly greater in GSTM1+ compared to GSTM1null asthmatics. Activation of
NF-kappaB activation in airway epithelial cells correlated with interleukin-8
concentrations and absolute neutrophil numbers in bronchoalveolar lavage fluid in
GSTM1+ but not GSTM1null asthmatics. CONCLUSIONS: Allergen-induced neutrophilic
airway inflammation in GSTM1+ asthmatics is associated with NF-kappaB activation
in airway epithelial cells in vivo. These novel data provide a potential
mechanism of the genomic link between GSTM1 polymorphism and airway neutrophilia
in atopic asthma.
PMID- 25118838
TI - Treatment of exertional heat stress developed during low or moderate physical
work.
AB - PURPOSE: We examined whether treatment for exertional heat stress via ice water
immersion (IWI) or natural recovery is affected by the intensity of physical work
performed and, thus, the time taken to reach hyperthermia. METHODS: Nine adults
(18-45 years; 17.9 +/- 2.8 percent body fat; 57.0 +/- 2.0 mL kg(-1) min(-1) peak
oxygen uptake) completed four conditions incorporating either walking or jogging
at 40 degrees C (20 % relative humidity) while wearing a non-permeable rain
poncho. Upon reaching 39.5 degrees C rectal temperature (Tre), participants
recovered either via IWI in 2 degrees C water or via natural recovery (seated in
a ~29 degrees C environment) until T re returned to 38 degrees C. RESULTS:
Cooling rates were greater in the IWI [Tre: 0.24 degrees C min(-1); esophageal
temperature (Tes): 0.24 degrees C min(-1)] than the natural recovery (Tre and
Tes: 0.03 degrees C min(-1)) conditions (p < 0.001) with no differences between
the two moderate and the two low intensity conditions (p > 0.05). Cooling rates
for T re and T es were greater in the 39.0-38.5 degrees C (Tre: 0.19 degrees C
min(-1); Tes: 0.31 degrees C min(-1)) compared with the 39.5-39.0 degrees C
(Tre: 0.11 degrees C min(-1); Tes: 0.13 degrees C min(-1)) period across
conditions (p < 0.05). Similar reductions in heart rate and mean arterial
pressure were observed during recovery across conditions (p > 0.05), albeit
occurred faster during IWI. Percent change in plasma volume at the end of natural
recovery and IWI was 5.96 and 9.58%, respectively (p < 0.001). CONCLUSION: The
intensity of physical work performed and, thus, the time taken to reach
hyperthermia does not affect the effectiveness of either IWI treatment or natural
recovery. Therefore, while the path to hyperthermia may be different for each
patient, the path to recovery must always be immediate IWI treatment.
PMID- 25118839
TI - Wavelet-based intensity analysis of the mechanomyograph and electromyograph
during the H-reflex.
AB - PURPOSE: The relationship between mechanomyography (MMG) and electromyography
(sEMG) during electrically evoked muscle contraction was examined using the von
Tscharner "intensity analysis," which describes the power of a non-stationary
signal as a function of both frequency and time. METHOD: Data for 8 college-aged
participants (3 males; 5 females) with measurable H-reflexes were analyzed.
Recruitment curves for H-reflex (H), M-wave (M) using sEMG, and peak-to-peak MMG
(MMGp-p) were elicited through incremental tibial nerve stimulation. The maximum
peak-to-peak values for H and M for each sample were summed (HM); and maximum
intensity values were measured for MMG, H, and M following the intensity analysis
and computation of total intensity (MMGCvT, HCvT, MCvT). HCvT and MCvT were
subsequently added together (HMCvT) for comparisons. RESULTS: Correlations of
HM:MMGp-p, HM:MMGCvT, HMCvT:MMGCvT, HMCvT:MMGp-p, were low (r = 0.34, 0.33, 0.09,
and 0.12, respectively, p < 0.001); and correlations of HM:HMCvT, MMGCvT:MMGp-p,
were moderate-to-high (r = 0.69 and 0.97, respectively, p < 0.001). Correlations
for individuals ranged from 0.61 to 0.99 across comparisons. The time at which
maximal intensities occurred reflected the transition from a predominant H-reflex
to the onset of the M-wave and declining lag times were noted with increasing
intensity. CONCLUSIONS: The intensity analysis provides insight into the
frequency characteristics of the H-reflex and M-wave not seen in traditional
analysis of the H-reflex. The intensity analysis may be a useful tool in studying
individual variations and changes in the contraction velocities of skeletal
muscle.
PMID- 25118840
TI - Age difference in efficiency of locomotion and maximal power output in well
trained triathletes.
AB - PURPOSE: The aim of this study was to examine the influence of age on cycling
efficiency and sprint power output in well-trained endurance masters athletes.
METHODS: The investigation was conducted on 60 healthy well-trained triathletes
separated into six separate groups (n = 10) depending on age: 20-29 years old; 30
39 years old; 40-49 years old; 50-59 years old; 60-69 years old; 70 years old.
Each participant attended the laboratory on three separate occasions to perform
(1) an incremental cycling test, (2) maximal peak sprint power test, involving
three 5-s sprint efforts (3) and a 10-min sub-maximal cycling test for
determination of cycling efficiency. RESULTS: Cycling efficiency decreased beyond
50 years (50-59 years compared with 20-29 years: -7.3 +/- 1.8%; p < 0.05) and
continued to decrease beyond 60 years (60-69 years compared with 50-59 years:
10.7 +/- 2.4%; p < 0.05), no further decrease was observed after 70 years. A
continuous impairment in maximal sprint power output was observed after the age
of 50 years leading to an overall decrease of 36% between 20-29 years and >70
years. Significant positive relationships were observed between maximal sprint
power output and both cycling efficiency (r(2) = 0.64, p < 0.05) and maximal
aerobic power (r(2) = 0.42 and p < 0.05). CONCLUSION: The present data indicates
a significant effect of ageing on cycling efficiency and maximal sprint power
output after 50 years and a significant relationship was found between these two
parameters.
PMID- 25118841
TI - Muscle synergies in preparation to a step made with and without obstacle.
AB - PURPOSE: To study multi-muscle synergies during preparation in making a step
(self-paced level stepping vs. obstacle crossing stepping). METHODS: The
uncontrolled manifold hypothesis was used to explore the organization of leg and
trunk muscles into groups (M-modes) and co-variation of M-mode involvement (M
mode synergies) during stepping tasks. Subjects performed two tasks: (1) making a
comfortable step from quiet stance (STCS), (2) stepping over an obstacle of 15%
body height from quiet stance, STOS. Electromyographic (EMG) signals of 10
postural muscles were recorded and analyzed. Principal component analysis was
used to identify M-modes within the space of integrated indices of muscle
activity. Variance in the M-mode space across stepping trials was partitioned
into two components, one that did not affect the average value of center of
pressure (COP) shift and the other that did. An index (DeltaV) corresponding to
the normalized difference between two components of variance was computed.
RESULTS: Under the two tasks, strong multi-M-mode synergies stabilizing
trajectories of the COP in the anterior-posterior direction were found. Despite
the significant differences in the COP shifts and EMG patterns of postural
adjustments, the synergies showed only minor differences across the conditions.
CONCLUSIONS: These findings demonstrate the robustness of multi-M-mode synergies
across different manners of making a step.
PMID- 25118842
TI - How standard is standard care? Exploring control group outcomes in behaviour
change interventions for young people with type 1 diabetes.
AB - OBJECTIVE: Poor descriptions of standard care may compromise interpretation of
results in randomised controlled trials (RCTs) of health interventions. We
investigated quality of standard care in RCTs of behaviour change interventions
for young people with type 1 diabetes and consider implications for evaluating
trial outcomes. DESIGN: We conducted systematic searches for articles published
between 1999 and 2012. We extracted standard care descriptions and contacted
trial authors to complete a checklist of standard care activities. The
relationship between standard care quality and outcomes was examined via subgroup
meta-analyses and meta-regression. MAIN OUTCOME MEASURES: Standard care
descriptions, standard care quality, and relationships between standard care
quality with medical and psychological outcomes. RESULTS: We identified 20 RCTs
described across 26 articles. Published descriptions of standard care were
limited to service-level features. Author responses indicated standard care
provision extended beyond published accounts. Subgroup analyses suggested control
groups receiving higher standard care quality showed larger improvements in both
medical and psychological outcomes, although standard care quality did not
predict outcomes significantly. CONCLUSION: The quality of care delivered to
control group participants can influence outcomes of RCTs. Inadequate reporting
exacerbates this issue by masking variations between trials. We argue for
increased clarity in reporting standard care in future trials.
PMID- 25118845
TI - Dual-lumen chest port infection rates in patients with head and neck cancer.
AB - PURPOSE: The aim of this study was to investigate dual-lumen chest port infection
rates in patients with head and neck cancer (HNC) compared to those with other
malignancies (non-HNC). MATERIALS AND METHODS: An IRB-approved retrospective
study was performed on 1,094 consecutive chest ports placed over a 2-year period.
Patients with poor follow-up (n = 53), no oncologic history (n = 13), or single
lumen ports (n = 183) were excluded yielding a study population of 845 patients.
The electronic medical records were queried for demographic information, data
regarding ports and infections, and imaging review. RESULTS: HNC patients
experienced more infections (42 vs. 30), an increased infection rate per 1,000
catheter days (0.68 vs. 0.21), and more early infections within 30 days compared
to non-HNC patients (10 vs. 6) (p < 0.001, p < 0.001, p = 0.02, respectively). An
existing tracheostomy at the time of port placement was associated with infection
in the HNC group (p = 0.02) but was not an independent risk factor for infection
in the study population overall (p = 0.06). There was a significant difference in
age, male gender, and right-sided ports between the HNC and non-HNC groups (p <
0.01, p < 0.001, and p = 0.01), although these were not found to be independent
risk factors for infection (p = 0.32, p = 0.76, p = 0.16). CONCLUSION: HNC
patients are at increased risk for infection of dual-lumen chest ports placed via
a jugular approach compared to patients with other malignancies. Tracheostomy is
associated with infection in HNC patients but is not an independent risk factor
for infection in the oncologic population as a whole.
PMID- 25118843
TI - [Multiple sclerosis : rehabilitation and long-term course].
AB - BACKGROUND: Multiple sclerosis (MS) is a highly complex disabling disease with
variable pathology and clinical course. Progressive multisystemic involvement of
the central nervous system leads to complex functional disturbances and
disabilities. Despite disease-modifying therapies and pharmacological symptomatic
treatment, the majority of MS patients develop progressive impairments in
functions, activities and quality of life in the long-term. Rehabilitation
interventions aim at improving symptoms and functional deficits and reducing the
negative impact on activities and social participation. OBJECTIVES: To evaluate
the impact and value of rehabilitation interventions in MS. METHODS: Specific
literature search in PubMed. RESULTS: Good evidence exists for a positive effect
of various rehabilitation interventions and multidisciplinary programs. Long-term
prognosis is very variable and depends on various influencing factors. Due to an
often unpredictable change of disease activity and the high variability, accurate
prediction of long-term prognosis in individual MS cases is still challenging.
CONCLUSION: Rehabilitation measures should be considered in an early phase of the
disease for maintaining functional abilities and reducing the risk of progression
of disabilities. Assignment to specific interventions and setting of
rehabilitation depend on disease-specific and personal factors and specific
goals. Monosyndromic or oligosyndromic impairments in the early phases of the
disease can be approached by targeted monodisciplinary ambulatory interventions,
whereas more severe and complex disabilities generally necessitate a more
intensive multidisciplinary rehabilitation.
PMID- 25118846
TI - Nuclear translocation of lysyl oxidase is promoted by interaction with
transcription repressor p66beta.
AB - Lysyl oxidase (LOX) is an amine oxidase involved in protein cross-linking of the
extracellular matrix. Less well characterized is the role that LOX plays among
nuclear proteins, and molecular mechanisms of its transport to the nucleus are
currently unknown. Here, we have employed yeast two-hybrid library screening and
found that the LOX catalytic domain interacts with the transcription repressor
p66beta. This interaction has been confirmed in vitro and has been found to be
accomplished through the CR2-containing domain of p66beta. Moreover, co
expression of p66beta and LOX in living tumor cells leads to the nuclear
accumulation of LOX. Thus, p66beta might be important for the regulation of LOX
in the nucleus.
PMID- 25118844
TI - [Statement of the German Ophthalmological Society, the Retina Society and the
Professional Association of German Ophthalmologists for intravitreal treatment of
macular edema in uveitis: Date: 02/07/2014].
PMID- 25118847
TI - Lung transplantation for advanced cystic lung disease due to nonamyloid kappa
light chain deposits.
AB - RATIONALE: Cystic lung light chain deposition disease (LCDD) is a severe and rare
form of nonamyloid kappa light chain deposits localized in the lung, potentially
leading to end-stage respiratory insufficiency. OBJECTIVES: To assess the outcome
after lung transplantation (LT) in this setting with particular attention to
disease recurrence. METHODS: We conducted a retrospective multicenter study of
seven patients who underwent LT for cystic lung LCDD in France between September
1992 and June 2012 in five centers. MEASUREMENTS AND MAIN RESULTS: In total, five
females and two males (mean age, 39.1 +/- 5.3 yr) underwent one single LT or
seven double LT (one retransplantation). Before LT, the patients showed a
constant obstructive ventilatory pattern with low carbon monoxide diffusing
capacity and resting hypoxemia. Lung computed tomography revealed widespread
cysts with occasional micronodulations. No extrapulmonary disease or plasma cell
neoplasm was detected. The serum-free kappa/lambda light chain ratio was
increased in three cases. The median follow-up after LT was 56 months (range, 1
110 mo). Kaplan-Meier survival was 85.7, 85.7, and 64.3% at 1, 3, and 5 years,
respectively. Three patients died from multiorgan failure (n = 1), chronic
rejection (n = 1), and breast cancer (n = 1) at 23 days, 56 months, and 96
months, respectively. At the end of follow-up, no patients showed recurrence on
imaging or histopathology. CONCLUSIONS: This small case series confirms that
cystic lung LCDD is a severe disease limited to the lung, affecting mostly young
females. LT appears to be a good therapeutic option allowing for satisfactory
long-term survival. We found no evidence of recurrence of the disease after LT.
PMID- 25118848
TI - Shopping behavior for ADHD drugs: results of a cohort study in a pharmacy
database.
AB - OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) medications are
subject to abuse, misuse, and diversion. Obtaining ADHD prescriptions from
multiple prescribers or filled across multiple pharmacies, known as 'doctor
shopping', may reflect such unsanctioned use. We sought to create a definition of
shopping behavior that differentiated ADHD medications from medications with low
risk of diversion, i.e. asthma medications, and describe the incidence,
frequency, and demography of shopping behavior. METHODS: This was a retrospective
cohort study in a pharmacy database-LRx-covering 65 % of US retail pharmacies.
Subjects had ADHD or asthma medication dispensed between February 2011 and
January 2012. We followed subjects for 18 months to assess the number with
overlapping dispensings from different prescribers, and the number of prescribers
and pharmacies involved in those dispensings. RESULTS: We included 4,402,464
subjects who were dispensed ADHD medications, and 6,128,025 subjects who were
dispensed asthma medications. Overlapping prescriptions from two or more
prescribers dispensed by three or more pharmacies was four times more frequent in
the ADHD cohort than in the asthma cohort. Using this definition, ADHD medication
shopping behavior was more common among experienced users than naive users, and
was most common in subjects aged 10-39 years. Among subjects who shopped, 57.4 %
shopped only once (accounting for 22.4 % of episodes), and 9.2 % shopped six or
more times (accounting for 42.0 % of episodes). Shoppers more often received
stimulant ADHD drugs than non-stimulants. CONCLUSIONS: Overlapping prescriptions
by different prescribers and filled at three or more pharmacies defines ADHD
medication shopping. Shopping behavior is most common in adolescents and younger
adults. A small proportion of shoppers is responsible for a large number of
shopping episodes.
PMID- 25118849
TI - Lower urinary tract symptoms in women with diabetes mellitus: a current review.
AB - A literature review of the most current publications studying lower urinary tract
symptoms (LUTS) and findings in diabetic women was conducted including articles
from January 2013 to April 2014. Current reports consistently note that aging and
obesity are significantly associated with worsened LUTS in diabetic women.
Glucosuria has variable effects on urodynamic parameters and LUTS, but has a
significant association with urinary tract infection (UTI) and incontinence at
clinically relevant numbers, such as HbA1C values. The presence of severe
nocturia in diabetic patients warrants careful surveillance for cardiovascular
risks given the significant association with mortality. Diabetics appear to be at
higher risk for colonization with the virulent, extended-spectrum, beta-lactamase
producing Escherichia coli and Klebsiella species in UTI. Novel therapies in
glycemic control and for diabetic bladder dysfunction are undergoing animal model
trials with encouraging results. The most promising of these includes stem cell
therapy, although a need exists for human studies.
PMID- 25118851
TI - Optimizing urology group partnerships: collaboration strategies and compensation
best practices.
AB - Market forces in health care have created substantial regulatory, legislative,
and reimbursement changes that have had a significant impact on urology group
practices. To maintain viability, many urology groups have merged into larger
integrated entities. Although group operations vary considerably, the majority of
groups have struggled with the development of a strong culture, effective
decision-making, and consensus-building around shared resources, income, and
expense. Creating a sustainable business model requires urology group leaders to
allocate appropriate time and resources to address these issues in a proactive
manner. This article outlines collaboration strategies for creating an effective
culture, governance, and leadership, and provides practical suggestions for
optimizing the performance of the urology group practice.
PMID- 25118850
TI - Impact of alpha blockers, 5-alpha reductase inhibitors and combination therapy on
sexual function.
AB - Medical treatments for lower urinary tract symptoms due to benign prostatic
hyperplasia are frequently associated with changes in sexual function. While
these medications are generally well-tolerated and have both reduced and delayed
more invasive surgical options, the ramifications of long-term chronic use are
largely unknown. Sexual side effects of these medications are frequently either
reported as part of a short-term initial drug study or have inflexible endpoints
that are not able to gauge more subtle changes in sexual performance. This review
will delineate the currently known effects of these medications on sexual
function and will consider mechanisms of dysfunction.
PMID- 25118852
TI - Robotic-assisted simple prostatectomy: is there evidence to go beyond the
experimental stage?
AB - Open simple prostatectomy (OSP) is an effective and durable treatment for select
patients with symptomatic benign prostatic hyperplasia (BPH) and large-volume
prostate glands (>80 cc), yet is associated with clinically significant risk of
bleeding, transfusion, prolonged hospital length of stay (LOS), and
complications. Robotic-assisted simple prostatectomy (RASP) potentially reduces
intraoperative blood loss and improves perioperative outcomes. Thirteen non
comparative series (Level 3 evidence) of RASP have established its safety and
efficacy and have demonstrated substantially decreased risk of transfusion,
complications, and mean LOS relative to published series of OSP, but with
consistently longer operative times. Comparative outcomes data (Level 1 and Level
2 evidence), however, are relatively lacking. Thus, while RASP has advanced
beyond the experimental stage, definitive outcomes studies are needed to
establish its benefits and costs relative to OSP and transurethral surgery.
PMID- 25118853
TI - The evaluation and management of refractory neurogenic overactive bladder.
AB - Patients with neurologic disease commonly develop overactive bladder (OAB)
symptoms of urgency, frequency, and/or urge incontinence that remain bothersome
despite oral pharmacologic therapy. Management of refractory OAB in the
neurogenic population is a complex issue with no uniform treatment strategy. When
treatment fails or patients generally are dissatisfied with the adverse effects
of oral therapy, available options include sacral neuromodulation, percutaneous
tibial nerve stimulation (PTNS), botulinum toxin injections, and lower urinary
tract reconstruction such as augmentation cystoplasty. A thorough knowledge and
understanding of available and emerging treatment options for neurogenic detrusor
overactivity is paramount to assisting clinicians in choosing an appropriate
treatment. This article reviews the non-pharmacologic treatment options for
neurogenic OAB, mainly botulinum toxin, neuromodulation, and lower urinary tract
reconstruction, and discusses important relevant studies.
PMID- 25118856
TI - Single-molecule electroluminescence and photoluminescence of polyfluorene unveils
the photophysics behind the green emission band.
AB - Optoelectronic properties of polyfluorene, a blue light-emitting organic
semiconductor, are often degraded by the presence of green emission that
originates mainly from oxidation of the polymer. Here, we use single-molecule
electroluminescence (EL) and photoluminescence (PL) spectroscopy on polyfluorene
chains confined in vertical cylinders of a phase-separated block copolymer to
spectrally resolve the green band and investigate in detail the photophysical
processes responsible for its appearance. In both EL and PL, a substantial
fraction of polyfluorene chains shows spectrally stable green emission which is
ascribed to a keto defect. In addition, in EL, we observe a new type of
vibrationally resolved spectra distributed over a wide range of frequencies and
showing strong spectral dynamics. Based on quantum chemical calculations, this
type is proposed to originate from charge-assisted formation and stabilization of
ground-state aggregates. The results are expected to have broad implications in
the fields of photophysics and material design of polyfluorene materials.
PMID- 25118855
TI - Neurogenic bladder: from diagnosis to management.
AB - Patients with spinal cord injury (SCI) present with a wide range and variety of
urologic manifestations, depending upon the level of injury. Historically,
patients with spinal cord injury experienced significant mortality related to
renal failure. Greater knowledge of the pathophysiology of SCI, however, has
contributed to a reduction in mortality. It is essential to perform a thorough
initial evaluation and regular follow-up of these patients to achieve the primary
goal of preservation of renal function, with the secondary goal of optimizing the
patient's quality of life.
PMID- 25118858
TI - Erratum to: Positive Affect Processing and Joint Attention in Infants at High
Risk for Autism: An Exploratory Study.
PMID- 25118854
TI - Surgical management of Peyronie's disease.
AB - Peyronie's disease (PD) has a significant impact on the quality of life of both
patients and their partners due to the compromised sexual function and physical
deformation resulting from the condition. PD is a connective tissue disorder
marked by fibrotic healing of the tunica albuginea, leading to penile deformities
including curvature, shortening, loss of girth, hourglass appearance, and
hinging. Despite the multiple medical therapies available, surgery is the gold
standard of treatment once the plaque has stabilized. We present a review of the
disease process, preoperative evaluation, operative planning, surgical treatments
with outcomes and complications, and nascent developments in surgical management
and graft development. Options include tunical lengthening procedures, tunical
shortening procedures, and penile prosthesis. Decision-making is governed by
degree of curvature, erectile function, and associated penile deformities. In
cases with curvature of less than 60-70 degrees, adequate penile length, and no
hourglass deformity, patients are candidates for tunical shortening procedures.
Patients with curvature greater than 60-70 degrees, penile hourglass or hinge
destabilizing deformities, and adequate erectile function should be counseled
with regard to tunical lengthening procedures. Patients with poor preoperative
erectile function should undergo inflatable penile prosthesis placement, with
possible secondary straightening procedures. Technique selection should be based
upon surgeon preference, expertise, and experience, as evidence does not
necessarily support one procedure over another.
PMID- 25118859
TI - In the eyes of residents good supervisors need to be more than engaged
physicians: the relevance of teacher work engagement in residency training.
AB - During their development into competent medical specialists, residents benefit
from their attending physicians' excellence in teaching and role modelling. Work
engagement increases overall job performance, but it is unknown whether this also
applies to attending physicians' teaching performance and role modelling.
Attending physicians in clinical teaching practice take on roles as doctors and
teachers. Therefore, this study (a) examined levels of attending physicians' work
engagement in both roles, and (b) quantified the relationships of both work
engagement roles to their teaching performance and role model status. In this
multicenter survey, residents evaluated attending physicians' teaching
performance and role model status using the validated System for Evaluation of
Teaching Qualities. Attending physicians self-reported their work engagement on a
7-point scale, separately for their roles as doctors and teachers, using the
validated 9-item Utrecht Work Engagement Scale. In total, 549 (68 %) residents
filled out 4,305 attending physician evaluations and 627 (78 %) attending
physicians participated. Attending physicians reported higher work engagement in
their doctor than in their teacher roles (mean difference: 0.95; 95 % CI 0.86
1.04; p < 0.001). Teacher work engagement was positively related to teaching
performance (regression coefficient, B: 0.11; 95 % CI 0.08-0.14; p < 0.001),
which in turn was positively associated to role model status (B: 1.08; 95 % CI
0.10-1.18; p < 0.001). In the eyes of residents, good supervisors need to be more
than engaged physicians, as attending physicians with high teacher work
engagement were evaluated as better teachers.
PMID- 25118860
TI - Identifying longitudinal growth trajectories of learning domains in problem-based
learning: a latent growth curve modeling approach using SEM.
AB - To determine the direction and extent to which medical student scores (as
observed by small-group tutors) on four problem-based-learning-related domains
change over nine consecutive blocks during a two-year period (Domains: Problem
Solving/Use of Information/Group Process/Professionalism). Latent growth curve
modeling is used to analyze performance trajectories in each domain of two
cohorts of 1st and 2nd year students (n = 296). Slopes of the growth trajectories
show similar linear increments in the first three domains. Further analysis
revealed relative strong individual variability in initial scores but not in
their later increments. Professionalism, on the other hand, shows low variability
and has very small, insignificant slope increments. In this study, we showed that
the learning domains (Problem Solving, Use of Information, and Group Process)
observed during PBL tutorials are not only related to each other but also develop
cumulatively over time. Professionalism, in contrast to the other domains
studied, is less affected by the curriculum suggesting that this represents a
stable characteristic. The observation that the PBL tutorial has an equal benefit
to all students is noteworthy and needs further investigation.
PMID- 25118857
TI - Randomized controlled trial comparing gastric cancer screening by
gastrointestinal X-ray with serology for Helicobacter pylori and pepsinogens
followed by gastrointestinal endoscopy.
AB - BACKGROUND: Based on the results of several case-control and cohort studies
gastrointestinal X-ray (GI X-ray) has been recommended for use in the nationwide
screening program for gastric cancer.. Although this was the only effective
screening program when almost all of the Japanese population were Helicobacter
pylori (H. pylori) positive, there has been concern whether an alternative
effective screening system should be established for the future H. pylori
negative generation. We therefore conducted the first randomized controlled trial
(RCT) comparing GI X-ray and gastrointestinal endoscopy (GIE) scheduled according
to results of serological testing (ST); this was done to determine the potential
for an alternative screening method. METHODS: Subjects who fulfilled the
inclusion criteria were residents between the ages of 30 and 74 and who were able
to receive gastric cancer screening in the Yurihonjo area. Participants were
assigned to the GI X-ray group or the GIE-ST group by computer randomization.
Subjects in each group were further subdivided into 4 categories according to
their different risks for gastric cancer. The feasibility of stratified
randomization was serologically assessed and detection rates of gastric cancer at
entry by the different screening methods were also compared. RESULTS: Of the
2,962 subjects invited, 1,206 individuals (41 percent) were included in the first
stage of this stratified RCT, and 604 and 602 individuals were assigned to the GI
X-ray group and the GIE-ST group, respectively. There were no statistically
significant differences in sex, age, height, body weight, smoking, alcohol intake
and family history of cancer between the 2 groups. During ST the GI X-ray group
showed a distribution that was not statistically different from that of the GIE
ST group. Although 3 cases of gastric cancer were detected in the GIE-ST group,
there was no statistically significant difference between the 2 groups. One
complication found was barium aspiration during the examination in the X-ray
group. CONCLUSION: We confirmed that baseline demographic features of the 2
groups were well balanced. We are now organizing the first RCT to compare the
existing screening method and the alternative method (Clinical trial registration
number: UMIN000005962).
PMID- 25118861
TI - Community of learners: charting learning in first year graduate entry medical
students during problem-based learning (PBL) study.
AB - This study considers social learning practices within and outside the overt
curriculum. A thematic approach was used to analyse data from six focus group
interviews with 11 graduate entry medical students from a UK university over a
year of study. The results indicate that: (1) during their first year of study
students form a community of learning practice, (2) this community of practice
influences learning inside and outside the overt curriculum, (3) there is a
changing community profile over the year of practice, (4) the students'
engagement in problem-based learning (PBL) as part of their overt curriculum
strongly influences the development of a community of practice and hence learning
both inside and outside the overt curriculum. Findings are discussed in terms of
Wenger's community of practice framework, the role of distributed cognition and
social learning. It is concluded that PBL is an effective approach for academics
to enrich students' social learning practices.
PMID- 25118862
TI - Rituals of Madness in the Practices of Place.
AB - While completing a PhD in literature with a focus on the practices of physical
and linguistic spaces, I was also working and sleeping (on call) at a dilapidated
house in a poorer part of Bristol in case I was needed by one of five paranoid or
clinically psychotic residents. I gave out medication in the morning, then went
home to study in a small rented room. I began to see ritual everywhere--in my
professors' routines; my own habits; the behaviours of the mentally ill patients.
This paper is the story of a number of madnesses and the problems with reading
ritual performance in everything we do.
PMID- 25118863
TI - Fairness norms and theory of mind in an ultimatum game: judgments, offers, and
decisions in school-aged children.
AB - The sensitivity to fairness undergoes relevant changes across development.
Whether such changes depend on primary inequity aversion or on sensitivity to a
social norm of fairness is still debated. Using a modified version of the
Ultimatum Game that creates informational asymmetries between Proposer and
Responder, a previous study showed that both perceptions of fairness and fair
behavior depend upon normative expectations, i.e., beliefs about what others
expect one should do in a specific situation. Individuals tend to comply with the
norm when risking sanctions, but disregard the norm when violations are
undetectable. Using the same methodology with children aged 8-10 years, the
present study shows that children's beliefs and behaviors differ from what is
observed in adults. Playing as Proposers, children show a self-serving bias only
when there is a clear informational asymmetry. Playing as Responders, they show a
remarkable discrepancy between their normative judgment about fair procedures (a
coin toss to determine the offer) and their behavior (rejection of an unfair
offer derived from the coin toss), supporting the existence of an outcome bias
effect. Finally, our results reveal no influence of theory of mind on children's
decision-making behavior.
PMID- 25118866
TI - Difficult needle decompression of bilateral tension pneumothoraces in an obese
female patient.
PMID- 25118865
TI - Evolution of inspiratory diaphragm activity in children over the course of the
PICU stay.
AB - PURPOSE: Diaphragm function should be monitored in critically ill patients, as
full ventilatory support rapidly induces diaphragm atrophy. Monitoring the
electrical activity of the diaphragm (EAdi) may help assess the level of
diaphragm activity, but such monitoring results are difficult to interpret
because reference values are lacking. The aim of this study was to describe EAdi
values in critically ill children during a stay in the pediatric intensive care
unit (PICU), from the acute to recovery phases, and to assess the impact of
ventilatory support on EAdi. METHODS: This was a prospective longitudinal
observational study of children requiring mechanical ventilation for >=24 h. EAdi
was recorded using a validated method in the acute phase, before extubation,
after extubation, and before PICU discharge. RESULTS: Fifty-five critically ill
children were enrolled in the study. Median maximum inspiratory EAdi (EAdimax)
during mechanical ventilation was 3.6 [interquartile range (IQR) 1.2-7.6] MUV in
the acute phase and 4.8 (IQR 2.0-10.7) MUV in the pre-extubation phase. Periods
of diaphragm inactivity (with no detectable inspiratory EAdi) were frequent
during conventional ventilation, even with a low level of support. EAdimax in
spontaneous ventilation was 15.4 (IQR 7.4-20.7) MUV shortly after extubation and
12.6 (IQR 8.1-21.3) MUV before PICU discharge. The difference in EAdimax between
mechanical ventilation and post-extubation periods was significant (p < 0.001).
Patients intubated mainly because of a lung pathology exhibited higher EAdi (p <
0.01), with a similar temporal increase. CONCLUSIONS: This is the first
systematic description of EAdi evolution in children during their stay in the
PICU. In our patient cohort, diaphragm activity was frequently low in
conventional ventilation, suggesting that overassistance or oversedation is
common in clinical practice. EAdi monitoring appears to be a helpful tool to
detect such situations.
PMID- 25118867
TI - Pathergy phenomenon: huge pyoderma gangrenosum following tube thoracostomy.
PMID- 25118869
TI - A large vertebral artery pseudoaneurysm due to percutaneous internal jugular vein
cannulation.
PMID- 25118868
TI - Mortality related to after-hours discharge from intensive care in Australia and
New Zealand, 2005-2012.
AB - INTRODUCTION: After-hours discharge from the intensive care unit (ICU) is
associated with adverse patient outcomes including increased ICU readmissions and
mortality. Since Australian and New Zealand data were last published, overall ICU
patient mortality has decreased; however it is unknown whether changes in
discharge practices have contributed to these improved outcomes. Our aim was to
examine trends over time in discharge timing and the contemporary associations
with mortality and ICU readmission. METHODS: Retrospective cohort study using
data from the Australian and New Zealand Intensive Care Society Adult Patient
Database (ANZICS APD) for patients admitted to Australian and New Zealand ICUs
between January 2005 and December 2012. Data collected included patient
characteristics, time of ICU discharge, hospital mortality and ICU readmissions.
RESULTS: Between 1 January 2005 and 31 December 2012, there were 710,535 patients
available for analysis, of whom 109,384 (15.4 %) were discharged after-hours
(1800-0600 hours). There were no changes in timing of ICU discharge over the 8
years of the study. Patients discharged after-hours had a higher hospital
mortality (6.4 versus 3.6 %; P < 0.001) and more ICU readmissions (5.1 versus 4.5
%; P < 0.001) than patients discharged in-hours. Although post-ICU mortality for
all patients declined during the study period, the risk associated with after
hours discharge remained elevated throughout (odds ratio 1.34, 95 % confidence
intervals 1.30-1.38). CONCLUSIONS: After-hours discharge remains an important
independent predictor of hospital mortality and readmission to ICU. Despite
widespread dissemination this evidence has not translated into fewer after-hours
discharges or reduction in risk in Australian and New Zealand hospitals.
PMID- 25118870
TI - Silk fibroin/collagen and silk fibroin/chitosan blended three-dimensional
scaffolds for tissue engineering.
AB - INTRODUCTION: In this study, the silk fibroin blended constructs were produced,
scaffold performances of different kinds of scaffold were analyzed, and the
better type for tissue engineering was optimized. METHODS: The silk
fibroin/collagen (SF/C) and silk fibroin/chitosan (SF/CS) were made using a
freeze-drying technique, porosity, water absorption expansion rate, mechanical
properties and pore size of different scaffold was detected. Bone marrow
mesenchymal stem cells (BMSCs) of 4-week-old male Wistar rats were separated by
density gradient centrifugation, third generation BMSCs were seeded onto
scaffolds, cultured 14 days, proliferation and metabolize of cells were detected
in different time using the thiazolyl blue tetrazolium bromide (MTT) assay
method, and cell morphology and distribution were observed by histological
analysis and scanning electron microscopy (SEM). RESULTS: Porosity, water
absorption expansion rate and Young's modulus of SF/C were significantly higher
than SF/CS (p < 0.05); pore size of SF/C and SF/CS was 103 +/- 12 and 76 +/- 11
MUm and had no significant differences between two types (p > 0.05); MTT results
showed that the metabolism of cells in the SF/C was better than SF/CS; after
cultivation for 14 days, in the inner zone of scaffolds, cells staining were
little or absent from SF/CS, lots of cells staining were existing in SF/C; pore
size was consistent, holes communicated with each other better, stem cells grew
well inside the scaffolds, extended fully and secreted much extracellular matrix
under SEM in SF/C scaffold; internal structure of SF/CS was disorder, holes size
were not consistent, and did not communicated with each other and cells were
partly dead. CONCLUSION: Compared with SF/CS, SF/C scaffold showed better
porosity, water absorption expansion rate, elasticity modulus and pore size,
cells grow well inside the scaffolds, and was more suitable for tissue
engineering.
PMID- 25118871
TI - Calcineurin-mediated regulation of hyphal growth, septation, and virulence in
Aspergillus fumigatus.
AB - Calcineurin is a heterodimeric protein phosphatase complex composed of catalytic
(CnaA) and regulatory (CnaB) subunits and plays diverse roles in regulating
fungal stress responses, morphogenesis, and pathogenesis. Fungal pathogens
utilize the calcineurin pathway to survive in the host environment and cause life
threatening infections. The immunosuppressive calcineurin inhibitors (FK506 and
cyclosporine A) are active against fungi, making calcineurin a promising
antifungal drug target. Here, we review novel findings on calcineurin
localization and functions in Aspergillus fumigatus hyphal growth and septum
formation through regulation of proteins involved in cell wall biosynthesis.
Extensive mutational analysis in the functional domains of A. fumigatus CnaA has
led to an understanding of the relevance of these domains for the localization
and function of CnaA at the hyphal septum. An evolutionarily conserved novel mode
of calcineurin regulation by phosphorylation in filamentous fungi was found to be
responsible for virulence in A. fumigatus. This finding of a filamentous fungal
specific mechanism controlling hyphal growth and virulence represents a potential
target for antifungal therapy.
PMID- 25118872
TI - Aspergillus: sex and recombination.
AB - The genus Aspergillus is one of the most widespread groups of fungi on Earth,
comprised of about 300-350 species with very diverse lifestyles. Most species
produce asexual propagula (conidia) on conidial heads. Despite their ubiquity, a
sexual cycle has not yet been identified for most of the aspergilli. Where sexual
reproduction is present, species exhibit either homothallic (self fertile) or
heterothallic (obligate outcrossing) breeding systems. A parasexual cycle has
also been described in some Aspergillus species. As in other fungi, sexual
reproduction is governed by mating-type (MAT) genes, which determine sexual
identity and are involved in regulating later stages of sexual development.
Previous population genetic studies have indicated that some supposedly asexual
aspergilli exhibit evidence of a recombining population structure, suggesting the
presence of a cryptic sexual cycle. In addition, genome analyses have revealed
networks of genes necessary for sexual reproduction in several Aspergillus
species, again consistent with latent sexuality in these fungi. Knowledge of MAT
gene presence has then successfully been applied to induce sexual reproduction
between MAT1-1 and MAT1-2 isolates of certain supposedly asexual aspergilli.
Recent progress in understanding the extent and significance of sexual
reproduction is described here, with special emphasis on findings that are
relevant to clinically important aspergilli.
PMID- 25118873
TI - Killed Saccharomyces cerevisiae protects against lethal challenge of Cryptococcus
grubii.
AB - Heat-killed Saccharomyces cerevisiae (HKY) vaccination protects mice against
aspergillosis, coccidioidomycosis, mucormycosis, or candidiasis. We studied HKY
protection against murine cryptococcosis. Once weekly subcutaneous HKY doses (S,
6 * 10(7); 2S, 1.2 * 10(8); 3S, 2.4 * 10(8)) began 28 (*3), 35 (*4), or 42 (*6)
days prior to intravenous Cryptococcus grubii infection. Survival through 28
days, and CFU in the organs of survivors, were compared to saline-vaccinated
controls. In the initial experiment, S, S*4, or 2S reduced brain CFU; liver or
spleen CFU was reduced by S*4 or 2S. In a more lethal second experiment, 2S*6,
2S, or 3S*4 improved survival, and HKY regimens reduced CFU in the brain, liver,
or spleen, with 2S*6, 2S, or 3S*4 most efficacious. Dose size appears more
important than the number of doses: Regimens >S were superior, and 2S and 2S*6
were equivalent. 2S and 3S were equivalent, suggesting doses >2S do not provide
additional protection. HKY protects against Cryptococcus, supporting components
of HKY as a basis for the development of a panfungal vaccine.
PMID- 25118874
TI - Killing rates for caspofungin against Candida albicans after brief and continuous
caspofungin exposure in the presence and absence of serum.
AB - It was previously demonstrated that brief (<=1 h) exposures to echinocandins are
as effective to kill Candida albicans cells as continuous 24-h exposure. However,
killing rates after continuous and short (1 h) echinocandin exposures to C.
albicans have not yet been evaluated in RPMI-1640 with and without 50 % serum. We
evaluated four echinocandin susceptible C. albicans bloodstream isolates, ATCC
10231 type strain and an echinocandin-resistant isolate (DPL20, FKS F645P).
Caspofungin MICs, time-kill and postantifungal effect (PAFE) tests were performed
in RPMI-1640 with and without 50 % serum. Killing rates (k values) in time-kill
and PAFE experiments were determined for each strain and concentration. In time
kill experiments, colony count decreases were isolate- and concentration
dependent at 0.25, 1, 4, 8, 16 and 32 mg/L in RPMI-1640, but concentration
independent at 1, 4, 8, 16 and 32 mg/L in 50 % serum. One-hour caspofungin
exposure at 4, 16 and 32 mg/L resulted in CFU decreases comparable with the
results obtained in time-kill experiments in RPMI-1640, but 50 % serum at 4, 16
and 32 mg/L allowed growth of all isolates (k values were negative) (P < 0.05
0.001). PAFE in 50 % serum decreased markedly at 4, 16 and 32 mg/L. Killing rates
remained high and concentration-independent in 50 % serum in case of continuous
but not in case of brief caspofungin exposure. As only a short growth inhibition
without killing was observed in 50 % serum, clinical relevance of caspofungin
PAFE in vivo is questionable.
PMID- 25118875
TI - Prevalence of Candida nivariensis and Candida bracarensis in vulvovaginal
Candidiasis.
AB - Candida nivariensis and Candida bracarensis were isolated from patients with
vulvovaginal candidiasis (VVC). Candida nivariensis and Candida bracarensis were
found in presumptive Candida glabrata isolates, which were identified using the
API Candida system. We retrospectively re-examined vaginal presumptive Candida
glabrata isolates for Candida nivariensis and Candida bracarensis from January 1,
2003, through December 31, 2012, via detection of the ITS1 region and the 5.8S
ribosomal RNA gene. Among 301 presumptive Candida glabrata isolates, 293 isolates
were confirmed as C. glabrata (97.34 %), 7 isolates were identified as C.
nivariensis (2.33 %) and 1 isolate was identified as C. bracarensis (0.33 %). The
C. nivariensis and C. bracarensis isolates were confirmed by sequencing. All C.
nivariensis isolates were susceptible to nystatin and susceptible or susceptible
dose-dependent to fluconazole, itraconazole, miconazole, and clotrimazole. The C.
bracarensis isolate was susceptible to nystatin and the tested azoles. Among the
seven patients with VVC caused by C. nivariensis and who were treated with
various antifungal agents, only one patient achieved mycological eradication at
both the day 7-14 and day 30-35 follow-ups. The C. bracarensis isolate was
isolated from a symptomatic pregnant woman; additional data for this patient were
unavailable. We conclude that C. nivariensis and C. bracarensis existed in the
vaginal samples of patients with VVC. Therapeutic efficacy in the patients with
C. nivariensis was poor and inconsistent with the observed in vitro antifungal
susceptibility, which requires further study.
PMID- 25118876
TI - Single-stage supramalleolar osteotomy for coronal plane deformity.
AB - A variety of surgical procedures are utilized for management of ankle
osteoarthritis. The most common etiology in patients with ankle osteoarthritis is
post-traumatic often resulting in asymmetric ankle osteoarthritis with
concomitant valgus or varus deformity. A substantial part of tibiotalar joint is
often preserved, therefore, in appropriate patients, joint-preserving surgery
holds the potential to be a superior treatment option than joint-sacrificing
procedures including total ankle replacement or ankle arthrodesis. This review is
designed to describe indications and contraindications for single-stage
supramalleolar realignment surgery. Complications associated with this type of
surgery and postoperative outcome are highlighted using recent literature.
PMID- 25118878
TI - Osteoporosis and the risk of symptomatic nephrolithiasis: a population-based 5
year follow-up study in Taiwan.
AB - This study estimates the risk of symptomatic nephrolithiasis within 5 years of
newly diagnosed osteoporosis in a Taiwan population. This cohort study consisted
of patients with a diagnosis of osteoporosis between Jan. 2003 and Dec. 2005 (N =
1634). Four age- and gender- matched patients for every patient in the study
cohort were selected using random sampling as the comparison cohort (N = 6536).
All patients were tracked for 5 years from the date of cohort entry to identify
whether they developed symptomatic nephrolithiasis. Cox proportional hazard
regressions were performed to evaluate the 5-year nephrolithiasis-free survival
rates. During the 5-year follow-up period, 60 osteoporosis patients (3.7%) and
165 non- osteoporosis patients (2.5%) developed symptomatic nephrolithiasis. The
adjusted HR of symptomatic nephrolithiasis was 1.38 times greater risk for
patients with osteoporosis than for the comparison cohort (95% confidence
interval (CI) 1.03-1.86; P < .05). Osteoporosis is very likely to be an
independent risk factor for subsequent diagnosis of symptomatic nephrolithiasis.
PMID- 25118877
TI - The prevalence of workaholism: a survey study in a nationally representative
sample of Norwegian employees.
AB - Workaholism has become an increasingly popular area for empirical study. However,
most studies examining the prevalence of workaholism have used non-representative
samples and measures with poorly defined cut-off scores. To overcome these
methodological limitations, a nationally representative survey among employees in
Norway (N = 1,124) was conducted. Questions relating to gender, age, marital
status, caretaker responsibility for children, percentage of full-time
equivalent, and educational level were asked. Workaholism was assessed by the use
of a psychometrically validated instrument (i.e., Bergen Work Addiction Scale).
Personality was assessed using the Mini-International Personality Item Pool.
Results showed that the prevalence of workaholism was 8.3% (95% CI = 6.7-9.9%).
An adjusted logistic regression analysis showed that workaholism was negatively
related to age and positively related to the personality dimensions
agreeableness, neuroticism, and intellect/imagination. Implications for these
findings are discussed.
PMID- 25118883
TI - Voyage to the bottom of the 'seaquence'.
PMID- 25118879
TI - Augmented efficacy with the combination of blockade of the Notch-1 pathway,
bortezomib and romidepsin in a murine MT-1 adult T-cell leukemia model.
AB - Adult T-cell leukemia (ATL) is an aggressive malignancy caused by human T-cell
lymphotropic virus-1. There is no accepted curative therapy for ATL. We have
reported that certain ATL patients have increased Notch-1 signaling along with
constitutive activation of the nuclear factor-kappaB pathway. Physical and
functional interaction between these two pathways provides the rationale to
combine the gamma-secretase inhibitor compound E with the proteasome inhibitor
bortezomib. Moreover, romidepsin, a histone deacetylase inhibitor, has
demonstrated major antitumor action in leukemia/lymphoma. In this study, we
investigated the therapeutic efficacy of the single agents and the combination of
these agents in a murine model of human ATL, the MT-1 model. Single and double
agents inhibited tumor growth as monitored by tumor size (P<0.05), and prolonged
survival of leukemia-bearing mice (P<0.05) compared with the control group. The
combination of three agents significantly enhanced the antitumor efficacy as
assessed by tumor size, tumor markers in the serum (human soluble interleukin-2
receptor-alpha and beta2-microglobulin) and survival of the MT-1 tumor-bearing
mice, compared with all other treatment groups (P<0.05). Improved therapeutic
efficacy obtained by combining compound E, bortezomib and romidepsin supports a
clinical trial of this combination in the treatment of ATL.
PMID- 25118884
TI - RAB11-mediated trafficking in host-pathogen interactions.
AB - Many bacterial and viral pathogens block or subvert host cellular processes to
promote successful infection. One host protein that is targeted by invading
pathogens is the small GTPase RAB11, which functions in vesicular trafficking.
RAB11 functions in conjunction with a protein complex known as the exocyst to
mediate terminal steps in cargo transport via the recycling endosome to cell-cell
junctions, phagosomes and cellular protrusions. These processes contribute to
host innate immunity by promoting epithelial and endothelial barrier integrity,
sensing and immobilizing pathogens and repairing pathogen-induced cellular
damage. In this Review, we discuss the various mechanisms that pathogens have
evolved to disrupt or subvert RAB11-dependent pathways as part of their infection
strategy.
PMID- 25118885
TI - Uniting the classification of cultured and uncultured bacteria and archaea using
16S rRNA gene sequences.
AB - Publicly available sequence databases of the small subunit ribosomal RNA gene,
also known as 16S rRNA in bacteria and archaea, are growing rapidly, and the
number of entries currently exceeds 4 million. However, a unified classification
and nomenclature framework for all bacteria and archaea does not yet exist. In
this Analysis article, we propose rational taxonomic boundaries for high taxa of
bacteria and archaea on the basis of 16S rRNA gene sequence identities and
suggest a rationale for the circumscription of uncultured taxa that is compatible
with the taxonomy of cultured bacteria and archaea. Our analyses show that only
nearly complete 16S rRNA sequences give accurate measures of taxonomic diversity.
In addition, our analyses suggest that most of the 16S rRNA sequences of the high
taxa will be discovered in environmental surveys by the end of the current
decade.
PMID- 25118886
TI - The impact of various platelet indices as prognostic markers of septic shock.
AB - INTRODUCTION: Platelet indices, including mean platelet volume (MPV), are readily
available blood tests, although their prognostic value in patients with septic
shock has not been fully explored. Current evidence has found contradictory
results. This study aims to explore the behavior of platelet indices in septic
shock and their clinical prognostic value. METHODS: Charts of septic shock
patients from January to December 2012 in a tertiary medical center in Northern
China were reviewed retrospectively. Platelet indices were recorded during the
first five consecutive days after admission, as well as the penultimate and the
last day of hospital stay. The data were compared between surviving and non
surviving patients. RESULTS: A total of 124 septic shock patients were enrolled.
Thirty-six of the patients survived and 88 of them expired. MPV in the non
survivor group was higher than that of the survivor group, especially on the last
day. PDW and PLCR showed increased trends, while PCT and PLT decreased in the non
survivor group. Among the PLT indices, MPV had the highest area under the
receiver operating characteristic curve (0.81) with a precision rate of 75.6% at
a cut-off of 10.5.Compared with other more usual septic shock prognostic markers,
MPV is second only to lactate for the highest area under the curve. CONCLUSION: A
statistically significant difference was seen between survivors and non-survivors
for platelet indices which make them easily available and useful prognostic
markers for patients in septic shock.
PMID- 25118887
TI - Megakaryocytic potentiating factor and mature mesothelin stimulate the growth of
a lung cancer cell line in the peritoneal cavity of mice.
AB - The mesothelin (MSLN) gene encodes a 71 kilodalton (kDa) precursor protein that
is processed into megakaryocytic potentiating factor (MPF), a 31 kDa protein that
is secreted from the cell, and mature mesothelin (mMSLN), a 40 kDa cell surface
protein. The mMSLN binds to CA125, an interaction that has been implicated in the
intra-cavitary spread of mesothelioma and ovarian cancer. To better define the
role of MPF and mMSLN, growth of the lung cancer cell line A549 was evaluated in
immuno-deficient mice with inactivation of the Msln gene. We observed that Msln-/
mice xenografted with intraperitoneal A549 tumors survive significantly long
than tumor-bearing Msln+/+ mice. When tumor-bearing Msln-/- mice are supplemented
with recombinant MPF (and to a lesser extent mMSLN), most of this survival
advantage is lost. These studies demonstrate that MPF and mMSLN have an important
role in the growth of lung cancer cells in vivo and raise the possibility that
inactivation of MPF may be a useful treatment for lung and other MSLN expressing
cancers.
PMID- 25118888
TI - Protective effect of magnesium and metformin on endometrium and ovary in
experimental diabetes mellitus.
AB - We evaluated the effect of magnesium and metformin on streptozotocin (STZ)
induced diabetes mellitus (DM) in non-pregnant female rats. The study comprised
four groups, each consisting of eight, non-pregnant, adult Wistar female rats
with a weight range of 170-250 g, maintained under the usual laboratory
conditions. One group of female rats was the control group that received no
treatment. To induce DM, the other three groups of animals received
streptozotocin (STZ), 60 mg/kg i.p. (in a single dose). The first STZ group
received no additional treatment. The second group received MgCl2 1 mmol/kg/day
i.p. daily, for eight weeks. The third group received daily metformin, 100
mg/kg/day per os (endogastric probe), for eight weeks. Blood glucose, total
plasma magnesium concentrations, and oxidative status were determined prior to,
24 hours and eight weeks after administration of the STZ. After eight weeks of
treatment, the animals were anesthetized and sacrificed. The uterus and ovaries
were removed and examined under optical microscopy. The data obtained were
analyzed statistically using the ANOVA test. The results showed that the number
of atretic ovarian follicles was 84%higher in the STZ-induced diabetes group
compared to the control group (p<0.01). The number of atretic follicles found in
the group receiving daily MgCl2 was 32% higher compared to the untreated control
group (p<0.05). The number of atretic follicles was increased by only 27% in the
metformin-treated group, as compared with the untreated control group.. The STZ
induced diabetes group presented an endometrial epithelial atrophy not seen in
the control group. MgCl2 administration attenuated the degree of endometrial
atrophy, there being an endometrial epithelial thickness of 19.43 +/- 0.51 MUm in
the STZ+MgCl2 group (p<0.05), as compared to a thickness of 13.51 +/- 0.27 MUm in
the STZ only-treated diabetic group.
PMID- 25118889
TI - BABYSCAN: a whole body counter for small children in Fukushima.
AB - BABYSCAN, a whole body counter for small children with a detection limit for
(137)Cs of better than 50 Bq/body, was developed, and the first unit has been
installed at a hospital in Fukushima, to help families with small children who
are very much concerned about internal exposures. The design principles,
implementation details and the initial operating experience are described.
PMID- 25118890
TI - Correction-less dosimetry of nonstandard photon fields: a new criterion to
determine the usability of radiation detectors.
AB - In the IAEA-AAPM dosimetry formalism, detector measurements in general
nonstandard conditions are corrected using the factor
k(f(clin),f(msr))(Q(clin),Q(msr)). This factor needs to be evaluated on a case-by
case basis which is difficult to accomplish in practice. The present paper aims
to provide a method that allows neglecting correction factors for small and
composite IMRT fields by first determining a radiation detector's usability in
these fields. Detailed models of nine radiation detectors are built: four
ionization chambers (NE2571, A12, A1SL, A14), three small field detectors
(PTW31018 microLion, PTW60003 natural diamond, PTW60012 unshielded diode) and two
near water-equivalent detectors (alanine, W1 scintillating fiber). Using the
egs_chamber Monte Carlo code, dose response functions at 6 MV and 25 MV are
sampled for each detector and their corresponding volume of water. These
functions are then used with a newly derived criterion to evaluate an upper bound
xi(f(ns),f(msr))(Q(ns),Q(msr)) on the variable
epsilon(f(ns),f(msr))(Q(ns),Q(msr)) if no field collimation/modulation occurs
over a given perturbation zone. The variable epsilon(f(ns),f(msr))(Q(ns),Q(msr))
is defined as the absolute value of the relative deviation from unity of a
nonstandard field quality correction factor k(f(ns),f(msr))(Q(ns),Q(msr)). Using
the same criterion, perturbation zones are evaluated by finding the smallest
field size allowed for correction-less dosimetry with a given tolerance
xi(f(ns),f(msr))(Q(ns),Q(msr)). For composite fields, the sensitivity of
detectors to the non-uniformity of virtual symmetric collapsed beams over regions
of interest specified by the criterion is studied to estimate an upper bound xi
(f(ns),f(ref))(Q(ns),Q) on epsilon(f(ns),f(ref))(Q(ns),Q) for a given beam
flatness. Finally, a newly defined perturbation function is used to minimize the
perturbations of the microLion chamber through density compensation. The
theoretical criterion shows good agreement with full Monte Carlo simulations of
epsilon(f(ns),f(msr))(Q(ns) Q(msr)). Perturbation zones are shown to be sensitive
to both the energy of the beam and the orientation of the detector. The density
compensated microLion shows significantly improved response in both axial and
radial orientations in small and composite IMRT fields. Finally, the new Exradin
W1 scintillator is shown to have xi(f(ns),f(msr))(Q(ns),Q(msr)) values under 1%
in small fields. The methods presented in this work theoretically show that
correction-less dosimetry of nonstandard field can be accomplished by knowing the
limit of usability of radiation detectors in these conditions. Potential
applications include small field output factor measurements and absolute absorbed
dose to water verification in the QA of clinical IMRT fields.
PMID- 25118891
TI - Association of cystatin C with measures of obesity and its impact on
cardiovascular events among healthy US adults.
AB - BACKGROUND: This study sought to explore the relationship between cystatin C
(CysC) and anthropometric measures of obesity and the influence of this
association on mortality [cardiovascular disease (CVD), coronary heart disease,
and all-cause] in a nationally representative population free of CVD, diabetes
mellitus, and macroalbuminuria (MA). METHODS: The study cohort included 4577
adult participants of the Third National Health and Nutrition Examination Survey
(NHANES). Spearman correlation analysis was performed to ascertain the
association between various anthropometric measures and CysC. Formal statistical
analyses of the interaction term between anthropometric measures and CysC for
outcomes were performed followed by stratified multivariate Cox proportional
hazard analyses. RESULTS: A moderate degree of association was seen between CysC
and measures of visceral adiposity as represented by waist-to-height ratio (WHR)
and waist circumference (WC) and only a weak association between CysC and body
mass index (BMI). CysC was predictive of all study outcomes in individuals with
normal anthropometric measurements only. CONCLUSIONS: CysC correlated better with
measures of visceral adiposity (WC and WHR) compared to BMI and appears to be a
better predictor of adverse cardiovascular outcomes among those with
anthropometric measures not suggestive of obesity compared to those with abnormal
measures of anthropometry.
PMID- 25118892
TI - Comments on the paper "Modelling of cell killing due to sparsely ionizing
radiation in normoxic and hypoxic conditions and an extension to high LET
radiation" by A. Mairani et al., Int. J. Radiat. Biol. 89(10), 2013, 782-793.
PMID- 25118893
TI - Short-term effects of extremely low frequency electromagnetic fields exposure on
Alzheimer's disease in rats.
AB - PURPOSE: With the development and widespread use of electromagnetic field (EMF)
technology, recent studies are focusing on the effects of EMF on human health.
Recently, extremely low frequency electromagnetic fields (ELF-EMF) have been
studied with great interest due to their possible effects on Alzheimer's disease
(AD). The objective of the present study was to investigate the interaction
between ELF-EMF exposure and memory impairment in rats. MATERIALS AND METHODS:
Twenty healthy male Sprague Dawley (SD) rats were randomly divided into two
groups (n = 10). Animals were exposed to 100 MUT/50 Hz ELF-EMF or subjected to
sham exposure when 12 weeks old. After 12 weeks, the Morris water maze (MWM) was
used to test the changes in cognitive and memory ability. Amyloid-beta (Abeta)
content in cortex, hippocampus and plasma were measured by ELISA assays. The
morphology of neuron was detected by H&E staining. RESULTS: After exposure, the
body weight of rats showed no difference compared with the control group. The
application of ELF-EMF did not induce any cognitive and memory impairment
compared with the sham-exposure group. The determination of Abeta showed no
significant change between the two groups, and there was no histological change
in ELF-EMF exposure group. CONCLUSION: The present study indicated that short
term exposure of 100 MUT/50 Hz ELF-EMF had no effects on cognition and memory of
rats, and did not alter the expression of Abeta and the neuron morphology.
However, more comprehensive studies are still required to elucidate the possible
effects and underlying mechanisms of ELF-EMF exposure on living organisms.
PMID- 25118896
TI - Poly(ADP-ribose) polymerase-1 (PARP1) and p53 labelling index correlates with
tumour grade in meningiomas.
AB - Meningiomas are one of the most frequent intracranial tumours, with 13
histological types and three grades according to the 2007 WHO Classification of
Tumours of the Central Nervous System. p53, as one of the most potent tumour
suppressor proteins, plays a role in nearly 50% of human tumours. Poly(ADP
ribose) polymerase (PARP) is a DNA repair enzyme with high ATP demand. It plays a
role in apoptosis by activating an apoptosis inducing factor, and in necrosis by
consuming NAD+ and ATP. Only PARP1 has been investigated in detail in tumours out
of the 17 members of the PARP superfamily; however, its role has not been studied
in meningiomas yet. The aim of this study was to determine the role of p53 and
PARP1 in meningiomas of different grade and to establish whether there is any
correlation between the p53 and PARP1 expression. Both PARP1 and p53 have been
expressed in all examined meningiomas. PARP1 labelled grade II tumours with a
higher intensity as compared to grade I and III neoplasms, respectively. An
increased p53 expression was noted in grade III meningiomas. There was no
statistical correlation between p53 and PARP1 expression. Our data indicate that
both PARP1 and p53 activation is a feature in meningiomas of higher grade, PARP1
overexpression being an early, whereas p53 overexpression, a late event in tumour
progression.
PMID- 25118895
TI - Blocking TRPV1 in nucleus accumbens inhibits persistent morphine conditioned
place preference expression in rats.
AB - The function of TRPV1 (transient receptor potential vanilloid subfamily, member
1) in the central nervous system is gradually elucidated. It has been recently
proved to be expressed in nucleus accumbens (NAc), a region playing an essential
role in mediating opioid craving and taking behaviors. Based on the general role
of TRPV1 antagonist in blocking neural over-excitability by both pre- and post
synaptic mechanisms, TRPV1 antagonist capsazepine (CPZ) was tested for its
ability to prohibit persistent opioid craving in rats. In the present study, we
assessed the expression of TRPV1 in nucleus accumbens and investigated the effect
of CPZ in bilateral nucleus accumbens on persistent morphine conditioned place
preference (mCPP) in rats. We also evaluated the side-effect of CPZ on activity
by comparing cross-beam times between groups. We found that morphine conditioned
place preference increased the TRPV1 expression and CPZ attenuated morphine
conditioned place preference in a dose-dependent and target-specific manner after
both short- and long-term spontaneous withdrawal, reflected by the reduction of
the increased time in morphine-paired side. CPZ (10 nM) could induce prolonged
and stable inhibition of morphine conditioned place preference expression. More
importantly, CPZ did not cause dysfunction of activity in the subjects tested,
which indicates the inhibitory effect was not obtained at the sacrifice of
regular movement. Collectively, these results indicated that injection of TRPV1
antagonist in nucleus accumbens is capable of attenuating persistent morphine
conditioned place preference without affecting normal activity. Thus, TRPV1
antagonist is one of the promising therapeutic drugs for the treatment of opioid
addiction.
PMID- 25118897
TI - Neuroprotective properties of ciliary neurotrophic factor on retinoic acid (RA)
predifferentiated SH-SY5Y neuroblastoma cells.
AB - Ciliary neurotrophic factor (CNTF) is a neurocytokine, which could promote
survival and/or differentiation in many cell types. In this study, the biological
effects of CNTF on retinoic acid (RA)-predifferentiated SH-SY5Y neuroblastoma
cells and the underlying molecular mechanism of this effect were investigated for
the first time. The results showed that RA was able to increase cells
susceptibility to CNTF via regulating the expression levels of CNTF receptors. A
further study revealed that CNTF could induce phosphorylation of STAT3, Akt and
ERK1/2 in RA-predifferentiated SH-SY5Y neuroblastoma cells, while the promoting
activity of CNTF on survival and neurite growth of cells was attenuated by co
treatment with JAK2 inhibitor AG490 (25 MUM), STAT3 inhibitor Curcumin (50 MUM),
PI3K inhibitor LY-294002 (50 uM), but not by co-treatment with MEK inhibitor
PD98059 (50 MUM). These findings suggested that JAK2/STAT3, as well as PI3K/Akt,
play important roles in mediating the survival and neurite growth response of RA
predifferentiated cells to CNTF. Our study may be useful to further understand
the functional role of CNTF and offer a convenient model to explore the
therapeutic potential of CNTF in neurodegenerative diseases.
PMID- 25118898
TI - Anaplastic transformation of low-grade gliomas (WHO II) on magnetic resonance
imaging.
AB - INTRODUCTION: Malignant transformation among gliomas WHO II ranges between 35%
and 89%. However, according to some reports, all gliomas WHO II undergo such
transformation over time. The aim of the study was to analyse MRI parameters
indicating anaplastic transformation of gliomas WHO II. MATERIAL AND METHODS:
Forty-six consecutive patients were enrolled in the study (20 females and 26
males; range of age 36 +/- 9 years) with supratentorial glioma WHO II.
Multiparametric MR examination included morphological imaging, perfusion-weighted
imaging, diffusion-weighted imaging and proton magnetic resonance spectroscopy.
Group division depended on the course of disease (ST - stable group, AT -
anaplastic transformation group). RESULTS: Subtotal tumour resection was achieved
in the whole AT group, whereas in the ST group, total tumour resection was
achieved in 10/29 (34%) patients. The size of the residual tumour after surgery
was statistically significantly higher in the AT group compared to the ST group
(AT: 51.5 cm3 +/- 37.7 vs. ST: 29.0 cm3 +/- 37.9; p = 0.011). Contrast
enhancement in the AT group occurred in 5/11 (45%) of tumours and in none of the
patients' areas of contrast enhancement were resected during surgery/biopsy.
However, the initial MR showed contrast enhancement in 10/29 (34%) of patients in
the ST group. The areas of contrast enhancement were totally resected in all
patients. Compared to the ST group tumours that underwent anaplastic
transformation had statistically significantly higher values of mean nrCBV and
max nrCBV on the initial MR, the follow-up and final MR examinations. However,
statistically significant differences between the groups in ADC values were
observed on the follow-up and final MR whereas mean Cho/Cr and mean Cho/NAA were
observed as late as on the final MR examination. CONCLUSIONS: Multiparametric MR
examination allows the detection of LGGs with high probability of rapid
anaplastic transformation and the detection of transformation prior to the
occurrence of contrast enhancement. The value of nrCBV is the most useful in the
diagnosis of anaplastic transformation. The resection of contrast enhancement
area of the tumour significantly increases time to anaplastic transformation of
LGGs.
PMID- 25118899
TI - Secretory meningiomas: immunohistochemical pattern of lectin and ultrastructure
of pseudopsammoma bodies.
AB - Secretory meningioma is an infrequent histological subtype of benign, WHO grade I
meningioma, that is characterized by focal epithelial and secretory
transformation of meningothelial cells. The leading histopathological feature of
neoplastic tissue is the presence of eosinophilic hyaline inclusions, defined as
"pseudopsammoma bodies". These inclusions are mostly intracytoplasmic, different
in size and often multiple. They are stained with periodic acid-Schiff (PAS) and
are immunopositive for epithelial and secretory markers. The aim of this study
was to determine the pattern of lectin bindings and ultrastructural features of
secretory meningiomas. The examination was performed on 8 cases of secretory
meningiomas that occurred in women and were mostly associated with prominent
peritumoural oedema. Histologically, the tumours exhibited numerous eosinophilic,
PAS positive pseudopsammoma bodies. Immunohistochemical studies revealed a
strong, ring-like cytokeratin expression around the pseudopsammoma bodies. The
inclusions were CEA and EMA positive but negative for vimentin. The
immunolabeling with four lectins (PNA, SBA, Con A and DBA) was studied. The
majority of pseudopsammoma bodies and surrounding tumour cells were strongly
labelled with PNA and SBA. Immunolabelling with Con A showed irregular staining
with high intensity in small inclusions. Immunostaining with DBA was seldom
positive in inclusions and negative in the tumour cell cytoplasm. Ultrastructure
of pseudopsammoma bodies exhibited advanced heterogeneity. The size of inclusions
and the content of intracytoplasmic lumina varied greatly. Some pseudopsammoma
bodies seemed to be located extracellularly and lacked the obvious lumina. Our
ultrastructural study and lectin binding pattern support the unique epithelial
and secretory transformation of neoplastic cells connected with their altered
glycosylation.
PMID- 25118900
TI - Effects of hypothermia on ex vivo microglial production of pro- and anti
inflammatory cytokines and nitric oxide in hypoxic-ischemic brain-injured mice.
AB - INTRODUCTION: Activated microglia produce neurotoxic factors, including pro
inflammatory cytokines and nitric oxide (NO), in response to neuronal
destruction. Therapeutic suppression of microglial release of these factors by
various approaches including hypothermia is considered to be neuroprotective
after severe brain damage. We examined the effects of hypothermic culture on the
production of pro- and anti-inflammatory cytokines and NO in ex vivo microglia
that were derived from mice with hypoxic-ischemic (HI) brain injury, through the
stimulation of toll-like receptors (TLRs) that play significant roles in the
pathological processes underlying a sterile central nervous system injury.
MATERIAL AND METHODS: Two-day-old mice underwent the right common carotid artery
ligation followed by 6% oxygen for 30 min, and thereafter were placed at 37
degrees C for 24 h, after which microglia were isolated and then cultured with
TLR2 and TLR4 agonists at 33 degrees C and 37 degrees C. Cytokine and NO levels
in culture supernatants were measured. RESULTS: Compared with 37 degrees C,
hypothermia (33 degrees C) reduced the production of tumour necrosis factor-alpha
(TNF-alpha: a pro-inflammatory cytokine) at 6 h and interleukin-10 (IL-10: an
anti-inflammatory cytokine) and NO at 48 h. CONCLUSIONS: In TLR-activated
microglia that were derived from mice with HI brain injury, hypothermia reduced
the production of TNF-alpha, IL-10, and NO temporally, a clinically relevant
finding suggesting that neuroprotection conferred by therapeutic hypothermia is
related to attenuation of early-phase and late-phase inflammatory factors as well
as that of late-phase anti-inflammatory factor(s) released from microglia.
PMID- 25118901
TI - Monitoring of very long-chain fatty acids levels in X-linked
adrenoleukodystrophy, treated with haematopoietic stem cell transplantation and
Lorenzo's Oil.
AB - X-linked adrenoleukodystrophy is a rare, neurodegenerative peroxisomal disorder
connected with mutation in the ABCD1 gene, causing impairment of the peroxisomal
beta-oxidation process and in consequence, accumulation of very long-chain fatty
acids (VLCFA) in blood and tissues. In this study we present serum very long
chain fatty acids levels during clinical course in an X-linked
adrenoleukodystrophy patient after haematopoietic stem cell transplantation
(HSCT) and on Lorenzo's Oil in a 11 years' period. The patient was diagnosed at
the age of 8 months by family screening. The administration of LO was started at
2 years of age. HSCT from a family donor was performed twice. VLCFA serum levels
were detected by the GC method. Chimaerism subsequent to HSCT was also analyzed.
Increasing very long-chain fatty acids levels correlate with a decreasing
chimaerism level after haematopoietic stem cell transplantation. The sequential
monitoring of very long-chain fatty acids serum levels is important and useful
for assessment of engraftment, graft failure or rejection.
PMID- 25118902
TI - Involvement of D1/D2 dopamine antagonists upon open-arms exploratory behaviours
induced by intra-nucleus accumbens shell administration of N-methyl-D-aspartate.
AB - Glutamatergic system stimulation in some parts of the brain may affect anxiety
related behaviours, aversive learning and memory. This system retains many
interactions with dopaminergic neurotransmission. We have studied the effect of
nucleus accumbens (NAc) shell glutamatergic system activation on anxiety-related
behaviours as well as aversive learning and memory in adult male Wistar rats
using the N-methyl-D-aspartate (NMDA) receptor agonist, NMDA. Furthermore, the
possible involvement of the NAc shell dopamine D1 and D2 receptors upon NMDA
induced effects was evaluated. The elevated plus-maze task was used to assess the
drugs' concomitant effects on anxiety, learning and memory in rats. All drugs
were delivered into the NAc shell via bilaterally implanted indwelling cannulae.
The NMDA-induced anxiolytic-like behaviours upon retest could possibly be
attributed to the further avoidance acquisition impairments. Moreover, the
inhibition of dopaminergic system using SCH 23390 and sulpiride induced an
anxiolytic-like response and impaired the aversive memory acquisition during
retest. However, the concurrent intra-NAc shell microinjection of the
subthreshold dose of SCH 23390 and sulpiride (0.125 ug/rat) reversed the
anxiolytic-like effect and blocked the aversive memory impairment induced by
intra-NAc shell NMDA. Our results suggest a modulatory role of the NAc shell
dopaminergic system on NMDA-induced effects in the aversive memory.
PMID- 25118903
TI - Neuroprotective effect of rotigotine against complex I inhibitors, MPP+ and
rotenone, in primary mesencephalic cell culture.
AB - INTRODUCTION: Dopamine agonists are suggested to be more efficacious in treating
Parkinson's disease (PD) as they have neuroprotective properties in addition to
their receptor-related actions. AIM OF THE STUDY: The present study was designed
to investigate the neuroprotective effects of rotigotine, a D3/D2/D1 dopamine
receptor agonist, against the two powerful complex I inhibitors, 1-methyl-4
phenylpyridinium (MPP+) and rotenone, in primary mesencephalic cell culture
relevant to PD. MATERIAL AND METHODS: Primary mesencephalic cell cultures were
prepared from embryonic mouse mesencephala at gestation day 14. Three sets of
cultures were treated with rotigotine alone, rotigotine and MPP+, and rotigotine
and rotenone to investigate the effect of rotigotine on the survival of
dopaminergic neurons against age-, MPP+- and rotenone-induced cell death. At the
end of each treatment, cultures were fixed and stained immunohistochemically
against tyrosine hydroxylase (TH). The effect of rotigotine against rotenone
induced reactive oxygen species (ROS) production was measured using CH-H2DCFDA
fluorescence dye. RESULTS: Rotigotine alone did not influence the survival of
tyrosine hydroxylase immunoreactive (THir) neurons except at 10 uM, it
significantly decreased the number of THir neurons by 40% compared to untreated
controls. Treatment of cultures with 0.01 uM rotigotine rescued 10% of THir
neurons against MPP+-induced cell death. Rotigotine was also found to
significantly rescue 20% of THir neurons at 0.01 uM of rotenone-treated cultures.
Using of CH-H2DCFDA fluorescence dye, it was found that rotigotine significantly
attenuated ROS production compared to rotenone-treated cultures. CONCLUSIONS:
Rotigotine provides minor protection against MPP+ and rescues a significant
number of THir neurons against rotenone in primary mesencephalic cell cultures
relevant to PD.
PMID- 25118904
TI - Primary angiitis of the central nervous system: a study of histopathological
patterns and review of the literature.
AB - Primary angiitis of the central nervous system (PACNS) is a rare form of
vasculitis of unknown aetiology. Multifaceted clinical manifestations, non
specific MRI findings, a broad range of differential diagnoses and diverse
pathological appearances prove to be a diagnostic challenge. However, a prompt
diagnosis and aggressive treatment are crucial to avoid permanent damage. Hence,
we present the clinico-pathological spectrum of this entity and highlight the
limitations of currently available diagnostic modalities. We describe in detail
the histopathological findings of eight cases of PACNS diagnosed at the
Department of Pathology, AIIMS, over a period of eight years. Eight cases of
PACNS were identified during this period. Five cases (62.5%) showed features of
granulomatous vasculitis, two (25%) showed lymphocytic vasculitis and one case
(12.5%) showed a predominantly necrotizing pattern of vasculitis. Diagnosis of
PACNS is a challenge and requires a high index of clinical suspicion. Appropriate
work-up to exclude other conditions is mandatory. Brain biopsy is useful in
making the diagnosis and ruling out mimicking conditions.
PMID- 25118905
TI - Dendritic and spinal alterations of neurons from Edinger-Westphal nucleus in
Alzheimer's disease.
AB - Alzheimer's disease (AD) is a heterogeneous neurodegenerative disorder, causing a
progressive decline of intellectual faculties, impairment of behavior and social
performance, and impairment of speech eloquence, associated with various
neurological manifestations based on a variable neuropathological background.
Edinger-Westphal nucleus is a selective target of Alzheimer pathology early in
the course of the disease. We attempted to determine the morphological
alterations of the dendrites and the dendritic spines in Edinger-Westphal nucleus
of 7 cases that fulfilled the diagnostic criteria for Alzheimer's disease. For
the histological study, we applied (a) routine neuropathological techniques and
(b) rapid Golgi method. We proceeded to 3D neuronal reconstruction for the
estimation of dendritic and spinal changes in Alzheimer's disease. The
morphological and morphometric analysis revealed a substantial neuronal loss and
synaptic alterations in Edinger-Westphal nucleus in all the cases of Alzheimer's
disease. Distal dendritic branches are prominently affected. The neuronal loss
and alteration of the spines in Edinger-Westphal nucleus in Alzheimer's disease
may be related to the exaggerated pupillary reaction to cholinergic antagonists.
Furthermore, the vulnerability of distal branches to Alzheimer's disease might be
related to neuroplasticity impairment.
PMID- 25118906
TI - Iron-induced fibrin formation may explain vascular pathology in Alzheimer's
disease.
PMID- 25118907
TI - A genomewide study of body mass index and its genetic correlation with
thromboembolic risk. Results from the GAIT project.
AB - Thrombosis and obesity are complex epidemiologically associated diseases. The
mechanism of this association is not yet understood. It was the objective of this
study to identify genetic components of body mass index (BMI) and their possible
role in the risk of thromboembolic disease. With the self-reported BMI of 397
individuals from 21 extended families enrolled in the GAIT (Genetic Analysis of
Idiopathic Thrombophilia) Project, we estimated the heritability of BMI and the
genetic correlation with the risk of thrombosis. Subjects were genotyped for an
autosomal genome-wide scan with 363 highly-informative DNA markers. Univariate
and bivariate multipoint linkage analyses were performed. The heritability for
BMI was 0.31 (p=2.9*10-5). Thromboembolic disease (including venous and arterial)
and BMI had a significant genetic correlation (rhoG=0.54, p=0.005). Two linkage
signals for BMI were obtained, one at 13q34 (LOD=3.36, p=0.0004) and other at
2q34, highly suggestive of linkage (LOD=1.95). Bivariate linkage analysis with
BMI and thrombosis risk also showed a significant signal at 13q34 (LOD=3),
indicating that this locus influences at the same time normal variation in the
BMI phenotype as well as susceptibility to thrombosis. In conclusion, BMI and
thrombosis are genetically correlated. The locus 13q34, which showed pleiotropy
with both phenotypes, contains two candidate genes, which may explain our linkage
pleiotropic signal and deserve further investigation as possible risk factors for
obesity and thrombosis.
PMID- 25118908
TI - Targeting Plasmodium falciparum transmission with primaquine: same efficacy,
improved safety with a lower dose?
AB - Malaria transmission is declining worldwide, leading to a growing interest in
strategies to reach elimination and eradication. Insecticide and drug resistance
threaten these efforts, driving an interest in the use of gametocytocidal drugs
to curb the spread of artemisinin resistance and accelerate the path to malaria
elimination. Primaquine is the only marketed drug that can kill mature Plasmodium
falciparum gametocytes, which can otherwise contribute to ongoing transmission
for long periods of time. While primaquine has been widely used in Asia and the
Americas, African countries have little experience with this drug and are
reluctant to use primaquine due to a fear of hemolytic side effects. We discuss
the underlying knowledge base and motivation to use primaquine as a P. falciparum
transmission blocker, revealing that while primaquine implementation can benefit
from further study, there remains an overall need for improved transmission
blocking drugs.
PMID- 25118910
TI - A mathematical model evaluating the timing of early diagnostic testing in HIV
exposed infants in South Africa.
AB - BACKGROUND: Antiretroviral therapy is often initiated too late to impact early
HIV-related infant mortality. Earlier treatment requires an earlier diagnosis,
and the currently recommended 6-week HIV polymerase chain reaction (PCR) test
needs reconsideration. This study aims to identify (1) optimal testing intervals
to maximize the number of perinatal HIV infections diagnosed and (2) programmatic
issues that impact diagnosis. METHODS: A mathematical model was developed to
simulate antiretroviral prophylaxis uptake and health outcomes in 240,000 HIV
exposed South African infants. The model considered routine early testing with 1
PCR (at birth, 6, 10, or 14 weeks of age) and with 2 PCR tests (at birth and at
6, 10, or 14 weeks of age). RESULTS: A single 6-week test would diagnose the same
number of perinatal HIV infections as birth testing (P = 0.92) but fewer
infections than a 10-week test (P < 0.01). Ten-week testing identifies the
highest number of perinatally infected infants (P < 0.01 compared with a single
test at all other ages) but does not save additional life years compared with
birth testing (P = 0.27). Performing 2 PCR tests (at birth and 10 weeks) would
identify the highest number of perinatal infections (P < 0.01 versus a second 6-
or 14-week test). However, 25% of perinatal HIV infections would remain
undiagnosed, largely because of failure to return PCR test results to caregivers.
CONCLUSIONS: Six weeks may no longer be the optimal age to diagnose perinatal HIV
infections. Two early PCR tests (at birth and 10 weeks) would likely be the ideal
diagnostic algorithm, but must be coupled with improved program coverage.
PMID- 25118911
TI - Differential co-expression analysis of rheumatoid arthritis with microarray data.
AB - The aim of the present study was to investigate the underlying molecular
mechanisms of rheumatoid arthritis (RA) using microarray expression profiles from
osteoarthritis and RA patients, to improve diagnosis and treatment strategies for
the condition. The gene expression profile of GSE27390 was downloaded from Gene
Expression Omnibus, including 19 samples from patients with RA (n=9) or
osteoarthritis (n=10). Firstly, the differentially expressed genes (DEGs) were
obtained with the thresholds of |logFC|>1.0 and P<0.05, using the t-test method
in LIMMA package. Then, differentially co-expressed genes (DCGs) and
differentially co-expressed links (DCLs) were screened with q<0.25 by the
differential coexpression analysis and differential regulation analysis of gene
expression microarray data package. Secondly, pathway enrichment analysis for
DCGs was performed by the Database for Annotation, Visualization and Integrated
Discovery and the DCLs associated with RA were selected by comparing the obtained
DCLs with known transcription factor (TF)-targets in the TRANSFAC database.
Finally, the obtained TFs were mapped to the known TF-targets to construct the
network using cytoscape software. A total of 1755 DEGs, 457 DCGs and 101988 DCLs
were achieved and there were 20 TFs in the obtained six TF-target relations
(STAT3-TNF, PBX1-PLAU, SOCS3-STAT3, GATA1-ETS2, ETS1-ICAM4 and CEBPE-GATA1) and
457 DCGs. A number of TF-target relations in the constructed network were not
within DCLs when the TF and target gene were DCGs. The identified TFs may have an
important role in the pathogenesis of RA and have the potential to be used as
biomarkers for the development of novel diagnostic and therapeutic strategies for
RA.
PMID- 25118912
TI - The third issue of 2014. Editorial.
PMID- 25118913
TI - Intervention program efficacy for spelling difficulties.
AB - OBJECTIVE: To develop an intervention procedure for spelling difficulties and to
verify the effectiveness of the intervention program in students with lower
spelling performance. METHOD: We developed an intervention program for spelling
difficulties, according to the semiology of the errors. The program consisted of
three modules totaling 16 sessions. The study included 40 students of the third
to fifth grade of public elementary education of the city of Marilia (SP), of
both genders, in aged of eight to 12 years old, being distributed in the
following groups: GI (20 students with lower spelling performance) and GII (20
students with higher spelling performance). In situation of pre and post-testing,
all groups were submitted to the Pro-Orthography. RESULTS: The results
statistically analyzed showed that, in general, all groups had average of right
that has higher in post-testing, reducing the types of errors second semiologycal
classification, mainly related to natural spelling errors. However, the results
also showed that the groups submitted to the intervention program showed better
performance on spelling tests in relation to not submitted. CONCLUSION: The
intervention program developed was effective once the groups submitted showed
better performance on spelling tests in relation to not submitted. Therefore, the
intervention program can help professionals in the Health and Education to
minimize the problems related to spelling, giving students an intervention that
is effective for the development of the spelling knowledge.
PMID- 25118914
TI - The lexical development of children with hearing impairment and associated
factors.
AB - PURPOSE: This study aimed at analyzing the association between the lexical
development of children with hearing impairment and their psychosocial and
socioeconomic characteristics and medical history. METHODS: An analytic
transversal study was conducted in an Auditive Health Attention Service. One
hundred and ten children from 6 to 10 years old using hearing aids and presenting
hearing loss that ranged from light to deep levels were evaluated. All children
were subjected to oral, written language and auditory perception tests. Parents
answered a structured questionnaire to collect data from their medical history
and socioeconomic status, and questionnaires about the features of the family
environment and psychosocial characteristics. Multivariate analysis was performed
by logistic regression, being the initial model composed by variables with p<0,20
in the univariate analysis. In the final model, we adopted a significance level
of 5%. RESULTS: The final model of the multivariate analysis showed an
association between the performance on the vocabulary test and the results of
phonemic discrimination test (OR=0.81; 95%CI 0.73-0.89). CONCLUSION: The results
show the importance of stimulating the auditory processing, particularly the
phonemic discrimination skill, throughout the rehabilitation process of children
with hearing impairment. This stimulation can enhance lexical development and
minimize the metalanguage and learning difficulties often observed in these
children.
PMID- 25118916
TI - Comparing the results of DAADD and ABC of children included in autism spectrum
disorders.
AB - PURPOSE: To verify if there are characteristic behaviors of the different
diagnosis included in the autism spectrum according to the Differential
Assessment of Autism and Other Developmental Disorders (DAADD) and to the Autism
Behavior Checklist (ABC). METHOD: Participants were 45 individuals and their
respective speech-language therapists. All therapists are graduate students
working with the children for at least 1 year. This time was considered
sufficient to the therapists to have the information required by the DAADD
questionnaire. It is comprised by 3 protocols specifically designed to children
with 2 to 4 years, 4 to 6 years and 6 to 8 years, the same criteria used to
separate the research groups, G1, G2 and G3, respectively. Data referring to the
ABC were retrieved from the subject's files at the Laboratorio de Investigacao
Fonoaudiologica nos Disturbios do Espectro do Autismo (Research Laboratory on
Language Disorders in the Autism Spectrum) of the School of Medicine,
Universidade de Sao Paulo, where it is routinely applied during the annual
assessment. RESULTS: Answers to the different areas of DAADD are similar to the
different areas of ABC. These data show data the diagnosis by DAADD is easier in
older children. Although there is no significant difference, the large occurrence
of Rett's syndrome diagnosis according to the DAADD was associated to higher risk
for autism according to the ABC in G1. With increasing age this tendency
decreases and either in G2 and G3 Autism is the most frequent diagnosis.
CONCLUSION: Although the results of both questionnaires tend to agree more with
increasing age, the DAADD is more sensitive in the different ages while the ABC
if more specific only to older children.
PMID- 25118915
TI - Mean length utterance in Brazilian children: a comparative study between Down
syndrome, specific language impairment, and typical language development.
AB - PURPOSE: To describe the linguistic performance of Brazilian Portuguese-speaking
children with Down syndrome by analyzing their Mean Length Utterance; to compare
their performance to that of children with Specific Language Impairment and
Typical Development; and to verify whether children with Down syndrome present
developmental language delay or disorder. METHOD: Participants were 25 children
with Down syndrome (Research Group), matched by mental age to a Control Group of
typically developing children, and to a Control Group of children with Specific
Language Impairment. Participants were divided into subgroups, according to age
range (three, four and five years). Speech samples were collected for the
Research Group, and the Mean Length Utterance was analyzed for morphemes and
words. RESULTS: Differences were observed between the performance of the Research
Group and both Control Groups, and the former presented inferior Mean Length
Utterance values for all age ranges, characterizing a delay in grammar and
general language development. CONCLUSION: The description of the linguistic
abilities of Brazilian Portuguese-speaking children with Down syndrome indicated
important grammatical deficits, especially regarding the use of functional words.
PMID- 25118917
TI - Global developmental abilities of cochlear implanted children with spastic
cerebral palsy: two experimental groups.
AB - PURPOSE: To analyze gross motor, fine motor-adaptive, language, social function
performance, and communicative behaviors among cochlear-implanted children with
spastic cerebral palsy (CP) and children with CP without hearing loss (HL) and to
compare them with children with normal development. METHODS: Prospective cross
sectional study involving 12 children with mean age of 63 months, distributed
into two experimental groups: G1-4 children with CP and cochlear implant (CI)
users and G2-4 children with CP without HL. A third group (G3) was the control
group with four typically developing children. In the experimental groups, six
children were classified in level II and two in level IV, using the Gross Motor
Function Classification System. We used the Denver Developmental Screening Test
II and the Communicative Behavior Observation (CBO). RESULTS: G3 showed better
performance than G1 and G2 in all evaluations. G2 showed better results than G1
in language, communication, personal-social, and fine motor-adaptive areas,
except in the gross motor area. Aspects of language and communicative behaviors
were lower in both experimental groups, especially in G1. Skills related to
personal-social area showed no differences among the groups. CONCLUSION: Motor
impairment of G1 and G2 and HL in G1 affected the development in the assessed
areas, but these factors did not restrict personal-social development. Children
with CP did not achieve high development in social function; however, the
difference with relation to G3 was not statically significant. The CI provided a
channel for oral language reception and social interaction, which has a key role
in determining the quality of life.
PMID- 25118918
TI - Otoacoustic emissions and biomarkers of oxidative stress in students of a tobacco
producing region.
AB - PURPOSE: To verify the association between the amplitude of distortion-product
otoacoustic emissions (DPOAE) and biomarkers of oxidative stress (OS) in resident
students of the tobacco-producing region. METHODS: Participated in the study
group (SG) 21 normal-hearing students from the tobacco-producing region, and in
the control group (CG) 25 normal-hearing students who did not live in the
countryside. The auditory system was assessed by DPOAE and the following
biomarkers: dichlorofluorescein diacetate (DCFH-DA) and micronucleus test (MN).
RESULTS: Both groups showed DPOAE present in both ears. Significant difference
was detected between groups--in the right ear in the frequency of 4.000 Hz and in
the left ear in the frequency of 2.000 Hz--with the mean amplitude of the DPOAE
of the SG lower than the one found in the CG. Considering both ears, the SG
presented lower mean across all frequencies and it was found a significant
difference in the frequencies of 2.000 and 4.000 Hz. The overall mean of DPOAE,
by ear, no significant differences were observed. In relation to the rate of
production of free radicals, the mean of the SG was significantly higher than
that of the mean of the CG. For the frequency of abnormal cells in the MN test,
the mean of the SG was also considerate significantly higher than the mean of the
CG. CONCLUSION: The SG showed a lower response level of DPOAE at all frequencies
and high levels of biomarkers of EO, however there was no association between
assessments.
PMID- 25118919
TI - Correlation of the findings of auditory steady-state evoked potential and of
behavioral hearing assessment in infants with sensorineural hearing loss.
AB - PURPOSE: To correlate the findings of an open-field audiometry with the
thresholds of steady-state auditory-evoked potentials (SSAEPs) found in infants
of up to 6 months of age with sensorineural hearing loss. METHODS: This study
included 19 infants with sensorineural hearing loss (8 males and 11 females),
with minimum age of 2 months and maximum age of 6 months. The SSAEPs were
assessed at 500 and 2000 Hz, and the audiometry was performed in open field
through observation of behavioral responses to sound stimuli, at the same
frequencies. RESULTS: We observed a significant correlation between the findings
of both tests conducted at 500 and 2000 Hz, with p-values of 0.002 and 0.013,
respectively. There was no statistical difference between ears (p=0.532) and
genders (p=0.615). CONCLUSION: We conclude that there was a significant
correlation between the SSAEP thresholds and the findings of the open-field
audiometry. Therefore, we can affirm that the SSAEPs are a viable examination,
able to predict the degree and configuration of hearing loss in infants of up to
6 months of age, and that they can be included in the clinical routine of hearing
assessments conducted in children.
PMID- 25118920
TI - Association between pharyngeal residue and posterior oral spillage with
penetration and aspiration in stroke.
AB - PURPOSE: This study aimed at showing association between the posterior oral
spillage and pharyngeal residue with tracheal aspiration and/or laryngeal
penetration in stroke. METHODS: Clinical cross-sectional retrospective
multicenter study. The study included 63 videofluoroscopic tests of post-ischemic
stroke individuals and oropharyngeal dysphagia data of the three reference
centers providing care for patients with dysphagia (43 men and 20 women; age
range: from 40 to 90 years). These individuals were divided into two groups.
Group I consisted of 35 participants with the presence of penetration and/or
laryngotracheal aspiration, and Group II consisted of 28 individuals with no
penetration and/or aspiration. Videofluoroscopic swallowing test results were
analyzed to divide the groups, and the presence of posterior oral spillage and
pharyngeal residue was observed. RESULTS: No association was found between the
groups with posterior oral spillage (chi2=1.65; p=0.30; phi2=0.02), but there was
statistical difference for the association between pharyngeal residue
(chi2=12.86; p=0.003; phi2=0.20) and the groups. CONCLUSION: There is an
association between pharyngeal residue and penetration with tracheal aspiration
in post-stroke individuals.
PMID- 25118921
TI - Evaluation of the force applied by the tongue and lip on the maxillary central
incisor tooth.
AB - PURPOSE: To describe the development and testing of a system that measures forces
exerted by the tongue and upper lip on a tooth during rest and during swallowing.
METHODS: Twenty-eight subjects, aged 19-31 years (mean: 23.2 years) were
submitted to measurement of forces exerted by the upper lip and tongue on the
maxillary right central incisor tooth. Flexiforce resistive sensors were fixed on
the labial and lingual surfaces of the tooth. They were connected to an amplifier
circuit and a data acquisition board for processing and transmitting information
to a computer. RESULTS: At rest, the tongue force on the tooth was 0.00+/-0.00 N
and the lip force on tooth was 0.02+/-0.02 N. The difference between them was
significant. During swallowing, the values were 0.31+/-0.38 N and 0.15+/-0.14 N,
for the tongue and lip, respectively. This difference was not significant.
CONCLUSION: At rest, the lip exerts a larger force than the tongue on the
maxillary right central incisor tooth. During swallowing, there was no difference
between lip and tongue force on the tooth.
PMID- 25118922
TI - National Policy on Health Care Hearing: an evaluative study from covering
services and diagnostic procedures.
AB - PURPOSE: To evaluate the National Policy on Hearing Health Care (PNASA) based on
the coverage of specialized services and diagnostic procedures in hearing health
care in Brazil. METHODS: This is an evaluation study focused on the coverage of
specialized services that offer moderate- and high-complexity diagnostic
procedures by region and in Brazil as a whole. We analyzed the data for the
period of 2004-2011 collected from the Unified Health System's Informatics
Department database (DATASUS), under the link "Information on health" and
tabulated using the software Tabwin. While collecting data from this platform, we
selected "procedures for diagnostic purposes", and the selected way of
organization was "diagnoses in otorhinolaryngology/audiology" of moderate and
high complexity. We estimated coverage and evolution of the number of procedures
according to the country's five geographic macroregions. RESULTS: We identified
an increase of 113% in service coverage and of 61% in the quantity of moderate-
and high-complexity hearing health diagnostic procedures throughout the country.
The northern region had an increase of 78% in the number of procedures, higher
than all other regions. However, a proportionally larger number of procedures
were performed in the southeast. We identified a significant increase in the
number of examinations of otoacoustic emissions (OAE) for hearing triage,
transient-evoked OAE and distortion product, as well as of diagnostic
reassessments of hearing loss in patients older than 3 years. CONCLUSION: There
has been an increase in services and actions in hearing health care in Brazil
since PNASA was implemented, but regional inequalities in the distribution of
these services still persist.
PMID- 25118923
TI - Tongue contour for /s/ and /?/ in children with speech sound disorder.
AB - PURPOSE: To describe the tongue shape for /s/ and /?/ sounds in three different
groups of children with and without speech sound disorder. METHODS: The six
participants were divided into three groups: Group 1--two typically developing
children, Group 2--two children with speech sound disorder presenting any other
phonological processes but not the ones involving the production of the /?/ and
Group 3--two children with speech sound disorder presenting any phonological
processes associated to the presence of the phonological process of palatal
fronting (these two children produced /?/ as /s/) aged between 5 and 8 years old,
all speakers of Brazilian Portuguese. The data were the words /'?avi/ (key) and
/'sapu/ (frog). Tongue contour was individually traced for the five productions
of each target word. RESULTS: The analysis of the tongue contour pointed to
evidences that both /s/ and /?/ were produced using distinct tongue contours for
G1 and G2. The production of these two groups was more stable than G3. The tongue
contour for /s/ and /?/ from the children in G3 was similar, indicating that
their production was undifferentiated. CONCLUSION: The use of the ultrasound
applied to the speech analysis was effective to confirm the perceptual analysis
of the sound made by the speech-language pathologist.
PMID- 25118924
TI - Cross-cultural adaptation of the Italian version of the Voice Activity
Participation Profile.
AB - The Vocal Activity Participation Profile (VAPP), originally developed in English,
is a self-assessment tool used to measure individuals' voice activity limitation
and participation restriction. Based on the fact that the cultural/linguistic
adaptation is an essential step of validating a protocol in another language, the
purpose was to linguistically and culturally adapt the VAPP into Italian. The
adaptation was performed in accordance to the Scientific Advisory Committee of
the Medical Outcomes Trust. The translation was performed by one bilingual speech
language pathologist and by one bilingual interpreter, who knew about the purpose
of this project. A bilingual English teacher, who had not participated in the
previous step, performed the back translation. A committee composed by three
speech-language pathologists specialized in voice and one laryngologist compared
the forward and backward translations, to assess for any discrepancies. A final
version was produced and called Profilo di Attivita e Partecipazione Vocale
(PAPV). A "not applicable" option was included to each item and was administered
to 17 individuals with voice problems, six males and 11 females, aged between 21
to 55 years. All items were relevant, as no patients chose the "not applicable"
option. However, four individuals, who had a lower educational level, did not
fully understand the instructions of the opening statement. Therefore, the
questionnaire was further reviewed and adjusted to clarify the information.
Otherwise, no items were changed and/or deleted. The PAPV kept the same structure
as the original version. The cultural equivalence of the Italian VAPP was
demonstrated and entitled PAPV, whose validation is currently in process.
PMID- 25118925
TI - Speech language therapy for cancer patients and new tendencies.
PMID- 25118926
TI - Non-apoptotic functions of caspase-7 during osteogenesis.
AB - Caspase-3 and -7 are generally known for their central role in the execution of
apoptosis. However, their function is not limited to apoptosis and under specific
conditions activation has been linked to proliferation or differentiation of
specialised cell types. In the present study, we followed the localisation of the
activated form of caspase-7 during intramembranous (alveolar and mandibular
bones) and endochondral (long bones of limbs) ossification in mice. In both bone
types, the activated form of caspase-7 was detected from the beginning of
ossification during embryonic development and persisted postnatally. The bone
status was investigated by microCT in both wild-type and caspase-7-deficient
adult mice. Intramembranous bone in mutant mice displayed a statistically
significant decrease in volume while the mineral density was not altered.
Conversely, endochondral bone showed constant volume but a significant decrease
in mineral density in caspase-7 knock-out mice. Cleaved caspase-7 was present in
a number of cells that did not show signs of apoptosis. PCR array analysis of the
mandibular bone of caspase-7-deficient versus wild-type mice pointed to a
significant decrease in mRNA levels for Msx1 and Smad1 in early bone formation.
These observations might explain the decrease in the alveolar bone volume of
adult knock-out mice. In conclusion, this study is the first to report a non
apoptotic function of caspase-7 in osteogenesis and also demonstrates further
specificities in endochondral versus intramembranous ossification.
PMID- 25118927
TI - Autophagy promotes paclitaxel resistance of cervical cancer cells: involvement of
Warburg effect activated hypoxia-induced factor 1-alpha-mediated signaling.
AB - Paclitaxel is one of the most effective chemotherapy drugs for advanced cervical
cancer. However, acquired resistance of paclitaxel represents a major barrier to
successful anticancer treatment. In this study, paclitaxel-resistant HeLa
sublines (HeLa-R cell lines) were established by continuous exposure and
increased autophagy level was observed in HeLa-R cells. 3-Methyladenine or ATG7
siRNA, autophagy inhibitors, could restore sensitivity of HeLa-R cells to
paclitaxel compared with parental HeLa cells. To determine the underlying
molecular mechanism, differentially expressed proteins between HeLa and HeLa-R
cells were identified by two-dimensional gel electrophoresis coupled with
electrospray ionization quadrupole time-of-flight MS/MS. We found glycolysis
associated proteins were upregulated in HeLa-R cell lines. Inhibition of
glycolysis by 2-deoxy-D-glucose or koningic acid could decrease autophagy and
enhance sensitivity of HeLa-R cells to paclitaxel. Moreover, glycolysis could
activate HIF1-alpha. Downregulation of HIF1-alpha by specific siRNA could
decrease autophagy and resensitize HeLa-R cells to paclitaxel. Taken together, a
possible Warburg effect activated HIF1-alpha-mediated signaling-induced
autophagic pathway is proposed, which may provide new insight into paclitaxel
chemoresistance.
PMID- 25118928
TI - The LRRK2 inhibitor GSK2578215A induces protective autophagy in SH-SY5Y cells:
involvement of Drp-1-mediated mitochondrial fission and mitochondrial-derived ROS
signaling.
AB - Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been associated
with Parkinson's disease, and its inhibition opens potential new therapeutic
options. Among the drug inhibitors of both wild-type and mutant LRRK2 forms is
the 2-arylmethyloxy-5-subtitutent-N-arylbenzamide GSK257815A. Using the well
established dopaminergic cell culture model SH-SY5Y, we have investigated the
effects of GSK2578215A on crucial neurodegenerative features such as
mitochondrial dynamics and autophagy. GSK2578215A induces mitochondrial
fragmentation of an early step preceding autophagy. This increase in
autophagosome results from inhibition of fusion rather than increases in
synthesis. The observed effects were shared with LRRK2-IN-1, a well-described,
structurally distinct kinase inhibitor compound or when knocking down LRRK2
expression using siRNA. Studies using the drug mitochondrial division inhibitor 1
indicated that translocation of the dynamin-related protein-1 has a relevant role
in this process. In addition, autophagic inhibitors revealed the participation of
autophagy as a cytoprotective response by removing damaged mitochondria.
GSK2578215A induced oxidative stress as evidenced by the accumulation of 4
hydroxy-2-nonenal in SH-SY5Y cells. The mitochondrial-targeted reactive oxygen
species scavenger MitoQ positioned these species as second messengers between
mitochondrial morphologic alterations and autophagy. Altogether, our results
demonstrated the relevance of LRRK2 in mitochondrial-activated pathways mediating
in autophagy and cell fate, crucial features in neurodegenerative diseases.
PMID- 25118929
TI - Stabilization of apoptotic cells: generation of zombie cells.
AB - Apoptosis is characterized by degradation of cell components but plasma membrane
remains intact. Apoptotic microtubule network (AMN) is organized during apoptosis
forming a cortical structure beneath plasma membrane that maintains plasma
membrane integrity. Apoptotic cells are also characterized by high reactive
oxygen species (ROS) production that can be potentially harmful for the cell. The
aim of this study was to develop a method that allows stabilizing apoptotic cells
for diagnostic and therapeutic applications. By using a cocktail composed of
taxol (a microtubule stabilizer), Zn(2+) (a caspase inhibitor) and coenzyme Q10
(a lipid antioxidant), we were able to stabilize H460 apoptotic cells in cell
cultures for at least 72 h, preventing secondary necrosis. Stabilized apoptotic
cells maintain many apoptotic cell characteristics such as the presence of
apoptotic microtubules, plasma membrane integrity, low intracellular calcium
levels and mitochondrial polarization. Apoptotic cell stabilization may open new
avenues in apoptosis detection and therapy.
PMID- 25118930
TI - Release and activity of histone in diseases.
AB - Histones and their post-translational modifications have key roles in chromatin
remodeling and gene transcription. Besides intranuclear functions, histones act
as damage-associated molecular pattern molecules when they are released into the
extracellular space. Administration of exogenous histones to animals leads to
systemic inflammatory and toxic responses through activating Toll-like receptors
and inflammasome pathways. Anti-histone treatment (e.g., neutralizing antibodies,
activated protein C, recombinant thrombomodulin, and heparin) protect mice
against lethal endotoxemia, sepsis, ischemia/reperfusion injury, trauma,
pancreatitis, peritonitis, stroke, coagulation, and thrombosis. In addition,
elevated serum histone and nucleosome levels have been implicated in multiple
pathophysiological processes and progression of diseases including autoimmune
diseases, inflammatory diseases, and cancer. Therefore, extracellular histones
could serve as biomarkers and novel therapeutic targets in human diseases.
PMID- 25118931
TI - Improving the therapeutic potential of endostatin by fusing it with the BAX BH3
death domain.
AB - Endostatin (ES) inhibits angiogenesis, reducing tumor growth in animal models.
However, it has low therapeutic effect in human clinical trials. BAX is a member
of the BCL-2 family of proteins; its proapoptotic (BH3) domain interacts with
other members of the family in the cytoplasm, to induce apoptosis. Here, we fused
the BAX BH3 domain with murine ES, to enhance ES potency. Endothelial cells
specifically internalize the fusion protein ES-BAX. The presence of the BAX
domain enhances endothelial cell death by apoptosis by 1.8-fold and diminishes
microvessel outgrowth in the rat aortic ring assay by 6.5-fold. Daily injections
of 15 MUg of ES-BAX/g in tumor-bearing mice reduce tumor weight by 86.9% as
compared with ES-treated animals. Co-immunoprecipitation assays confirmed that ES
BAX interacts with members of the BCL-2 family. Also, ES interacts with BCL-2,
BCL-XL, and BAK in endothelial cell lysates, suggesting a potential new mechanism
for the apoptosis induction by ES. The superiority of the ES-BAX antiangiogenic
effect indicates that this fusion protein could be a promising therapeutic
alternative to treat cancer.
PMID- 25118932
TI - Cholesterol oxidase from Bordetella species promotes irreversible cell apoptosis
in lung adenocarcinoma by cholesterol oxidation.
AB - Cholesterol oxidase (COD), an enzyme catalyzing the oxidation of cholesterol, has
been applied to track the distribution of membrane cholesterol. Little
investigations about the effect of COD on tumor cells have been performed. In the
present study, we provided evidence that COD from Bordetella species (COD-B),
induced apoptosis of lung cancer cells in vitro and in vivo. COD-B treatment
inhibited Akt and ERK1/2 phosphorylation in dose- and time-dependent manner,
which was not reversed and was even aggravated by cholesterol addition. Further
investigation indicated that COD-B treatment promoted the generation of reactive
oxygen species (ROS) and that cholesterol addition further elevated ROS levels.
Moreover, COD-B treatment resulted in JNK and p38 phosphorylation, downregulation
of Bcl-2, upregulation of Bax, activated caspase-3 and cytochrome C release,
which likely responded to freshly produced hydrogen peroxide that accompanied
cholesterol oxidation. Catalase pretreatment could only partially prevent COD-B
induced events, suggesting that catalase inhibited H2O2-induced signal
transduction but had little effect on signal pathways involved in cholesterol
depletion. Our results demonstrated that COD-B led to irreversible cell apoptosis
by decreasing cholesterol content and increasing ROS level. In addition, COD-B
may be a promising candidate for a novel anti-tumor therapy.
PMID- 25118933
TI - The protease Omi regulates mitochondrial biogenesis through the GSK3beta/PGC
1alpha pathway.
AB - Loss of the mitochondrial protease activity of Omi causes mitochondrial
dysfunction, neurodegeneration with parkinsonian features and premature death in
mnd2 (motor neuron degeneration 2) mice. However, the detailed mechanisms
underlying this pathology remain largely unknown. Here, we report that Omi
participates in the process of mitochondrial biogenesis, which has been linked to
several neurodegenerative diseases. The mitochondrial biogenesis is deficit in
mnd2 mice, evidenced by severe decreases of mitochondrial components,
mitochondrial DNA and mitochondrial density. Omi cleaves glycogen synthase kinase
3beta (GSK3beta), a kinase promoting PPARgamma coactivator-1alpha (PGC-1alpha)
degradation, to regulate PGC-1alpha, a factor important for the mitochondrial
biogenesis. In mnd2 mice, GSK3beta abundance is increased and PGC-1alpha
abundance is decreased significantly. Inhibition of GSK3beta by SB216763 or
overexpression of PGC-1alpha can restore mitochondrial biogenesis in mnd2 mice or
Omi-knockdown N2a cells. Furthermore, there is a significant improvement of the
movement ability of mnd2 mice after SB216763 treatment. Thus, our study
identified Omi as a novel regulator of mitochondrial biogenesis, involving in Omi
protease-deficient-induced neurodegeneration.
PMID- 25118934
TI - Specific antibody binding to the APP672-699 region shifts APP processing from
alpha- to beta-cleavage.
AB - Alzheimer's disease (AD), a progressive neurodegenerative disorder that is the
most common cause of dementia in the elderly, is characterized by the
accumulation of amyloid-beta (Abeta) plaques and neurofibrillary tangles, as well
as a progressive loss of synapses and neurons in the brain. The major
pertinacious component of amyloid plaques is Abeta, a variably sized peptide
derived from the integral membrane protein amyloid precursor protein (APP). The
Abeta region of APP locates partly within its ecto- and trans-membrane domains.
APP is cleaved by three proteases, designated as alpha-, beta-, and gamma
secretases. Processing by beta- and gamma-secretase cleaves the N- and C-terminal
ends of the Abeta region, respectively, releasing Abeta, whereas alpha-secretase
cleaves within the Abeta sequence, releasing soluble APPalpha (sAPPalpha). The
gamma-secretase cleaves at several adjacent sites to yield Abeta species
containing 39-43 amino acid residues. Both alpha- and beta-cleavage sites of
human wild-type APP are located in APP672-699 region (ectodomain of beta-C
terminal fragment, ED-beta-CTF or ED-C99). Therefore, the amino acid residues
within or near this region are definitely pivotal for human wild-type APP
function and processing. Here, we report that one ED-C99-specific monoclonal
antibody (mAbED-C99) blocks human wild-type APP endocytosis and shifts its
processing from alpha- to beta-cleavage, as evidenced by elevated accumulation of
cell surface full-length APP and beta-CTF together with reduced sAPPalpha and
alpha-CTF levels. Moreover, mAbED-C99 enhances the interactions of APP with
cholesterol. Consistently, intracerebroventricular injection of mAbED-C99 to
human wild-type APP transgenic mice markedly increases membrane-associated beta
CTF. All these findings suggest that APP672-699 region is critical for human wild
type APP processing and may provide new clues for the pathogenesis of sporadic
AD.
PMID- 25118937
TI - Depletion of intermediate filament protein Nestin, a target of microRNA-940,
suppresses tumorigenesis by inducing spontaneous DNA damage accumulation in human
nasopharyngeal carcinoma.
AB - Nasopharyngeal carcinoma (NPC) is a major malignant tumor of the head and neck
region in southern China. The understanding of its underlying etiology is
essential for the development of novel effective therapies. We report for the
first time that microRNA-940 (miR-940) significantly suppresses the proliferation
of a variety of cancer cell lines, arrests cells cycle, induces caspase-3/7
dependent apoptosis and inhibits the formation of NPC xenograft tumors in mice.
We further show that miR-940 directly binds to the 3'-untranslated regions of
Nestin mRNA and promotes its degradation. Likewise, depletion of Nestin inhibits
tumor cell proliferation, arrest cells at G2/M, induces apoptosis and suppresses
xenograft tumor formation in vivo. These functions of miR-940 can be reversed by
ectopic expression of Nestin, suggesting that miR-940 regulates cell
proliferation and survival through Nestin. Notably, we observed reduced miR-940
and increased Nestin levels in NPC patient samples. Protein microarray revealed
that knockdown of Nestin in 5-8F NPC cells alters the phosphorylation of proteins
involved in the DNA damage response, suggesting a mechanism for the miR
940/Nestin axis. Consistently, depletion of Nestin induced spontaneous DNA damage
accumulation, delayed the DNA damage repair process and increased the sensitivity
to irradiation and the chemotherapeutic agent doxorubicin. Collectively, our
findings indicate that Nestin, which is downregulated by miR-940, can promote
tumorigenesis in NPC cells through involvement in the DNA damage response. The
levels of microRNA-940 and Nestin may serve as indicators of cancer status and
prognosis.
PMID- 25118935
TI - Impaired cell death and mammary gland involution in the absence of Dock1 and Rac1
signaling.
AB - Throughout life, the tight equilibrium between cell death and the prompt
clearance of dead corpses is required to maintain a proper tissue homeostasis and
prevent inflammation. Following lactation, mammary gland involution is triggered
and results in the death of excessive epithelial cells that are rapidly cleared
by phagocytes to ensure that the gland returns to its prepregnant state.
Orthologs of Dock1 (dedicator of cytokinesis 1), Elmo and Rac1 (ras-related C3
botulinum toxin substrate 1) in Caenorhabditis elegans are part of a signaling
module in phagocytes that is linking apoptotic cell recognition to cytoskeletal
reorganization required for engulfment. In mammals, Elmo1 was shown to interact
with the phosphatidylserine receptor Bai1 and relay signals to promote
phagocytosis of apoptotic cells. Still, the role of the RacGEF Dock1 in the
clearance of dying cells in mammals was never directly addressed. We generated
two mouse models with conditional inactivation of Dock1 and Rac1 and revealed
that the expression of these genes is not essential in the mammary gland during
puberty, pregnancy and lactation. We induced mammary gland involution in these
mice to investigate the role of Dock1/Rac1 signaling in the engulfment of cell
corpses. Unpredictably, activation of Stat3 (signal transducer and activator of
transcription 3), a key regulator of mammary gland involution, was impaired in
the absence of Rac1 and Dock1 expression. Likewise, failure to activate properly
Stat3 was coinciding with a significant delay in the initiation and progression
of mammary gland involution in mutant animals. By using an in vitro phagocytosis
assay, we observed that Dock1 and Rac1 are essential to mediate engulfment in
epithelial phagocytes. In vivo, cell corpses accumulated at late time points of
involution in Dock1 and Rac1 mutant mammary glands. Overall, our study
demonstrated an unsuspected role for Dock1/Rac1 signaling in the initiation of
mammary gland involution, and also suggested a role for this pathway in the
clearance of dead cells by epithelial phagocytes.
PMID- 25118938
TI - Detrimental effects of Notch1 signaling activated by cadmium in renal proximal
tubular epithelial cells.
AB - We examined the roles of Notch1 signaling and its cross-talk with other signaling
pathways, including p53 and phosphatidylinositol-3-kinase (PI3K)/Akt, in cadmium
induced cellular damage in HK-2 human renal proximal tubular epithelial cells.
Following exposure to cadmium chloride (CdCl2), the level of Notch intracellular
domain (NICD), the cleaved form of the Notch1 receptor, was increased and
accumulated in the nuclear fraction. Knockdown of Notch1 with siRNA or treatment
with the gamma-secretase inhibitor, DAPT (N-[N-(3,5-difluorophenacetyl-L-alanyl)]
S-phenylglycine t-butyl ester), prevented CdCl2-induced morphological change of
HK-2 cells and reduction of cell viability. Knockdown of Jagged1 or Jagged2, the
ligands of the Notch1 receptor, partially suppressed cadmium cytotoxicity.
Inhibition of p53 activity with pifithrin-alpha or inhibition of PI3K with
LY294002 suppressed CdCl2-induced cellular damage and elevation of Notch1-NICD.
In addition, treatment with the epidermal growth factor receptor (EGFR)
inhibitor, AG1478, and the insulin-like growth factor-1 receptor inhibitor, PPP,
suppressed both Notch1-NICD accumulation and Akt phosphorylation in HK-2 cells
exposed to CdCl2. However, knockdown of Notch1 did not affect CdCl2-induced p53
accumulation and phosphorylation but suppressed phosphorylation of EGFR, Akt, and
p70 S6 kinase. Depletion of Notch1 suppressed CdCl2-induced reduction of E
cadherin expression and elevation of Snail expression. Furthermore, treatment
with SB216763, an inhibitor of glycogen synthase kinase-3, suppressed the potency
of LY294002 treatment to reduce Snail expression in HK-2 cells exposed to CdCl2.
Knockdown of Snail with siRNA partially prevented HK-2 cells from CdCl2-induced
reduction of E-cadherin expression and cellular damage. These results suggest
that cadmium exposure induces the activation of Notch1 signaling in renal
proximal tubular cells with cooperative activation by the p53 and PI3K/Akt
signaling pathways; the resultant expression of Snail, a repressor of E-cadherin
expression, might lead to cellular damage by decreasing cell-cell adhesion.
PMID- 25118939
TI - FAK competes for Src to promote migration against invasion in melanoma cells.
AB - Melanoma is one of the most deadly cancers because of its high propensity to
metastasis, a process that requires migration and invasion of tumor cells driven
by the regulated formation of adhesives structures like focal adhesions (FAs) and
invasive structures like invadopodia. FAK, the major kinase of FAs, has been
implicated in many cellular processes, including migration and invasion. In this
study, we investigated the role of FAK in the regulation of invasion. We report
that suppression of FAK in B16F10 melanoma cells led to increased invadopodia
formation and invasion through Matrigel, but impaired migration. These effects
are rescued by FAK WT but not by FAK(Y397F) reexpression. Invadopodia formation
requires local Src activation downstream of FAK and in a FAK phosphorylation
dependant manner. FAK deletion correlates with increased phosphorylation of Tks-5
(tyrosine kinase substrate with five SH3 domain) and reactive oxygen species
production. In conclusion, our data show that FAK is able to mediate opposite
effects on cell migration and invasion. Accordingly, beneficial effects of FAK
inhibition are context dependent and may depend on the cell response to
environmental cues and/or on the primary or secondary changes that melanoma
experienced through the invasion cycle.
PMID- 25118942
TI - Future impacts of nitrogen deposition and climate change scenarios on forest
crown defoliation.
AB - Defoliation is an indicator for forest health in response to several stressors
including air pollutants, and one of the most important parameters monitored in
the International Cooperative Programme on Assessment and Monitoring of Air
Pollution Effects on Forests (ICP Forests). The study aims to estimate crown
defoliation in 2030, under three climate and one nitrogen deposition scenarios,
based on evaluation of the most important factors (meteorological, nitrogen
deposition and chemical soil parameters) affecting defoliation of twelve European
tree species. The combination of favourable climate and nitrogen fertilization in
the more adaptive species induces a generalized decrease of defoliation. On the
other hand, severe climate change and drought are main causes of increase in
defoliation in Quercus ilex and Fagus sylvatica, especially in Mediterranean
area. Our results provide information on regional distribution of future
defoliation, an important knowledge for identifying policies to counteract
negative impacts of climate change and air pollution.
PMID- 25118941
TI - Visceral adipose tissue-derived serine protease inhibitor inhibits interleukin
1beta-induced catabolic and inflammatory responses in murine chondrocytes.
AB - Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a newly
identified member of the adipocytokine family, whose precise role in chondrocyte
metabolism remains to be elucidated. The aim of the present study was to
investigate the effect of vaspin on chondrocytes. The cell viability and the
cytotoxicity of vaspin in chondrocytes were examined. Furthermore, the gene
expression of matrix metalloproteinases-2 and -9, a disintegrin and
metalloproteinase with thrombospondin motifs 4 and 5 and cathepsin D was also
examined, as well as the protein production of cyclooxygenase-2, prostaglandin E2
and inducible nitrous oxide synthase following treatment with different
concentrations of vaspin in the absence or presence of interleukin-1-beta (IL
1beta). In addition, the protein levels of the inhibitor of nuclear factor-kappaB
(IkappaB-alpha) and the phosphorylation of nuclear factor kappa B (NF-kappaB)
were investigated. Vaspin was not able to stimulate the proliferation of
chondrocytes and demonstrated no significant cytotoxic effect at concentrations
of 10-500 ng/ml following coincubation for 24 and 48 h. However, vaspin inhibited
IL-1beta-induced production of catabolic factors and inflammatory mediators in
chondrocytes, and also suppressed the phosphorylation of NF-kappaB and the
degradation of IkappaB-alpha. The data from the present study suggested that
vaspin has a protective effect in chondrocyte metabolism and is an important
factor in the pathophysiology of osteoarthritis.
PMID- 25118943
TI - D'scent of man: a comparative survey of primate chemosignaling in relation to
sex.
AB - This article is part of a Special Issue (Chemosignals and Reproduction). As
highly visual animals, primates, in general, and Old World species (including
humans), in particular, are not immediately recognized for reliance in their
daily interactions on olfactory communication. Nevertheless, views on primate
olfactory acuity and the pervasiveness of their scent signaling are changing,
with increased appreciation for the important role of body odors in primate
social and sexual behavior. All major taxonomic groups, from lemurs to humans,
are endowed with scent-producing organs, and either deposit or exude a wealth of
volatile compounds, many of which are known semiochemicals. This review takes a
comparative perspective to illustrate the reproductive context of primate
signaling, the relevant information content of their signals, the sexually
differentiated investigative responses generated, and the behavioral or
physiological consequences of message transmission to both signaler and receiver.
Throughout, humans are placed alongside their relatives to illustrate the
evolutionary continuum in the sexual selection of primate chemosignals. This ever
growing body of evidence points to a critical role of scent in guiding the social
behavior and reproductive function throughout the primate order.
PMID- 25118940
TI - Impulsivity in disorders of food and drug misuse.
AB - BACKGROUND: Evidence suggests some overlap between the pathological use of food
and drugs, yet how impulsivity compares across these different clinical disorders
remains unclear. Substance use disorders are commonly characterized by elevated
impulsivity, and impulsivity subtypes may show commonalities and differences in
various conditions. We hypothesized that obese subjects with binge-eating
disorder (BED) and abstinent alcohol-dependent cohorts would have relatively more
impulsive profiles compared to obese subjects without BED. We also predicted
decision impulsivity impairment in obesity with and without BED. METHOD: Thirty
obese subjects with BED, 30 without BED and 30 abstinent alcohol-dependent
subjects and age- and gender-matched controls were tested on delay discounting
(preference for a smaller immediate reward over a larger delayed reward),
reflection impulsivity (rapid decision making prior to evidence accumulation) and
motor response inhibition (action cancellation of a prepotent response). RESULTS:
All three groups had greater delay discounting relative to healthy volunteers.
Both obese subjects without BED and alcohol-dependent subjects had impaired motor
response inhibition. Only obese subjects without BED had impaired integration of
available information to optimize outcomes over later trials with a cost
condition. CONCLUSIONS: Delay discounting appears to be a common core impairment
across disorders of food and drug intake. Unexpectedly, obese subjects without
BED showed greater impulsivity than obese subjects with BED. We highlight the
dissociability and heterogeneity of impulsivity subtypes and add to the
understanding of neurocognitive profiles across disorders involving food and
drugs. Our results have therapeutic implications suggesting that disorder
specific patterns of impulsivity could be targeted.
PMID- 25118944
TI - Successful non-surgical deep uterine transfer of porcine morulae after 24 hour
culture in a chemically defined medium.
AB - Excellent fertility and prolificacy have been reported after non-surgical deep
uterine transfers of fresh in vivo-derived porcine embryos. Unfortunately, when
this technology is used with vitrified embryos, the reproductive performance of
recipients is low. For this reason and because the embryos must be stored until
they are transferred to the recipient farms, we evaluated the potential
application of non-surgical deep uterine transfers with in vivo-derived morulae
cultured for 24 h in liquid stage. In Experiment 1, two temperatures (25 degrees
C and 37 degrees C) and two media (one fully defined and one semi-defined) were
assessed. Morulae cultured in culture medium supplemented with bovine serum
albumin and fetal calf serum at 38.5 degrees C in 5% CO2 in air were used as
controls. Irrespective of medium, the embryo viability after 24 h of culture was
negatively affected (P<0.05) at 25 degrees C but not at 37 degrees C compared
with the controls. Embryo development was delayed in all experimental groups
compared with the control group (P<0.001). Most of the embryos (95.7%) cultured
at 37 degrees C achieved the full or expanded blastocyst stage, and unlike the
controls, none of them hatched at the end of culture. In Experiment 2, 785
morulae were cultured in the defined medium at 37 degrees C for 24 h, and the
resulting blastocysts were transferred to the recipients (n = 24). Uncultured
embryos collected at the blastocyst stage (n = 750) were directly transferred to
the recipients and used as controls (n = 25). No differences in farrowing rates
(91.7% and 92.0%) or litter sizes (9.0 +/- 0.6 and 9.4 +/- 0.8) were observed
between the groups. This study demonstrated, for the first time, that high
reproductive performance can be achieved after non-surgical deep uterine
transfers with short-term cultured morulae in a defined medium, which opens new
possibilities for the sanitary, safe national and international trade of porcine
embryos and the commercial use of embryo transfer in pigs.
PMID- 25118945
TI - Perinatal protein malnutrition affects mitochondrial function in adult and
results in a resistance to high fat diet-induced obesity.
AB - Epidemiological findings indicate that transient environmental influences during
perinatal life, especially nutrition, may have deleterious heritable health
effects lasting for the entire life. Indeed, the fetal organism develops specific
adaptations that permanently change its physiology/metabolism and that persist
even in the absence of the stimulus that initiated them. This process is termed
"nutritional programming". We previously demonstrated that mothers fed a Low
Protein-Diet (LPD) during gestation and lactation give birth to F1-LPD animals
presenting metabolic consequences that are different from those observed when the
nutritional stress is applied during gestation only. Compared to control mice,
adult F1-LPD animals have a lower body weight and exhibit a higher food intake
suggesting that maternal protein under-nutrition during gestation and lactation
affects the energy metabolism of F1-LPD offspring. In this study, we investigated
the origin of this apparent energy wasting process in F1-LPD and demonstrated
that minimal energy expenditure is increased, due to both an increased
mitochondrial function in skeletal muscle and an increased mitochondrial density
in White Adipose Tissue. Importantly, F1-LPD mice are protected against high-fat
diet-induced obesity. Clearly, different paradigms of exposure to malnutrition
may be associated with differences in energy expenditure, food intake, weight and
different susceptibilities to various symptoms associated with metabolic
syndrome. Taken together these results demonstrate that intra-uterine environment
is a major contributor to the future of individuals and disturbance at a critical
period of development may compromise their health. Consequently, understanding
the molecular mechanisms may give access to useful knowledge regarding the onset
of metabolic diseases.
PMID- 25118950
TI - Near surface magnetic domain observation with ultra-high resolution.
AB - Near field magnetic force microscopy (NF-MFM) has been demonstrated to locally
observe the magnetic fine structures in nanosized recording bits at an operating
distance of 1 nm. The nanoscale magnetic domains, the polarity of surface
magnetic charges, as well as the 3D magnetic fields leaking from the bits are
investigated via NF-MFM with a soft NiFe tip. A Fourier analysis of the images
suggests that the magnetic moment can be determined locally in a volume as small
as 5 nanometers. The NF-MFM is crucial to the analysis of surface magnetic
features and allows a wide range of future applications, for example, in data
storage and biomedicine.
PMID- 25118949
TI - Modulation of gene expression in endothelial cells in response to high LET nickel
ion irradiation.
AB - Ionizing radiation can elicit harmful effects on the cardiovascular system at
high doses. Endothelial cells are critical targets in radiation-induced
cardiovascular damage. Astronauts performing a long-term deep space mission are
exposed to consistently higher fluences of ionizing radiation that may accumulate
to reach high effective doses. In addition, cosmic radiation contains high linear
energy transfer (LET) radiation that is known to produce high values of relative
biological effectiveness (RBE). The aim of this study was to broaden the
understanding of the molecular response to high LET radiation by investigating
the changes in gene expression in endothelial cells. For this purpose, a human
endothelial cell line (EA.hy926) was irradiated with accelerated nickel ions (Ni)
(LET, 183 keV/um) at doses of 0.5, 2 and 5 Gy. DNA damage was measured 2 and 24 h
following irradiation by gamma-H2AX foci detection by fluorescence microscopy and
gene expression changes were measured by microarrays at 8 and 24 h following
irradiation. We found that exposure to accelerated nickel particles induced a
persistent DNA damage response up to 24 h after treatment. This was accompanied
by a downregulation in the expression of a multitude of genes involved in the
regulation of the cell cycle and an upregulation in the expression of genes
involved in cell cycle checkpoints. In addition, genes involved in DNA damage
response, oxidative stress, apoptosis and cell-cell signaling (cytokines) were
found to be upregulated. An in silico analysis of the involved genes suggested
that the transcription factors, E2F and nuclear factor (NF)-kappaB, may be
involved in these cellular responses.
PMID- 25118947
TI - Transcriptome analysis of red swamp crawfish Procambarus clarkii reveals genes
involved in gonadal development.
AB - BACKGROUND: The red swamp crawfish, Procambarus clarkii, has become one of the
most economically important cultured species in China. Currently, little is known
about the gonadal development of this species. Isolation and characterization of
genes are an initial step towards understanding gonadal development of P.
clarkii. RESULTS: Using the 454 pyrosequencing technology, we obtained a total of
1,134,993 high quality sequence reads from the crawfish testis and ovary
libraries. We aimed to identify different genes with a potential role in gonad
development. The assembly formed into 22,652 isotigs, distributed by GO analysis
across 55 categories in the three ontologies, 'molecular function', 'cellular
component', and 'biological processes'. Comparative transcript analysis showed
that 1,720 isotigs in the ovary were up-regulated and 2138 isotigs were down
regulated. Several gonad development related genes, such as vitellogenin, cyclin
B, cyclin-dependent kinases 2, Dmc1 and ubiquitin were identified. Quantitative
real-time PCR verified the expression profiles of 14 differentially expressed
genes, and confirmed the reliability of the 454 pyrosequencing. CONCLUSIONS: Our
findings provide an archive for future research on gonadal development at a
molecular level in P. clarkii and other crustacean. This data will be helpful to
develop new ideas for artificial regulation of the reproductive process in
crawfish aquaculture.
PMID- 25118952
TI - A tailor-made nucleoside-based colourimetric probe of formic acid.
AB - A ratiometric, specific probe of formic acid has been developed. It is based on
intermolecular nucleobase-pairing of inosine-capped plasmonic nanoparticles to
form nucleoside channels, which are destabilised by the analyte.
PMID- 25118951
TI - A population-based study of corneal arcus and its risk factors in Iran.
AB - PURPOSE: To determine the prevalence of corneal arcus, its risk factors, and its
relationship to ocular and visual indices. METHODS: In this cross-sectional
study, 300 clusters were randomly selected from Shahroud in the north of Iran,
using multistage sampling. A total of 20 people were invited to participate from
each cluster. After enrollment, all optometric, biometric and ophthalmic exams
were conducted on site. RESULTS: Of 6311 people invited, 5190 (82.2%)
participated in the study. The prevalence of corneal arcus was 23.3% (95%
confidence interval, CI, 22.1-24.6), and 98.4% were bilateral cases. The
prevalence of corneal arcus was higher in men (odds ratio, OR, 2.02, 95% CI 1.8
2.3, p < 0.001) and increased with age (OR 1.1/year, p < 0.001). In a
multivariable-adjusted regression model, age (OR 1.1/year, p = 0.006), male sex
(OR 1.30, p = 0.001), diabetes (OR 0.7, p < 0.001), smoking (OR 1.5, p = 0.003),
outdoor activity (OR 1.4, p = 0.006), systolic blood pressure (OR 1.01, p =
0.012), and diastolic blood pressure (OR 0.99, p = 0.016) were significantly
correlated with corneal arcus. Including biometric components in another model,
corneal thickness (OR 0.99, p < 0.001), anterior chamber depth (OR 0.68, p <
0.001) and corneal radius of curvature (OR 1.59, p < 0.001) were significantly
correlated with corneal arcus. CONCLUSION: This study adds valuable information
to the epidemiology of corneal arcus in Iran and the Middle East. In people aged
over 60 years, nearly 50% of the study population had corneal arcus. Older age,
male sex, smoking, and systolic hypertension were risk factors for corneal arcus.
Corneal arcus was also associated with thin and flat corneas and shallow anterior
chamber depth.
PMID- 25118953
TI - Functional analyses on antioxidant, anti-inflammatory, and antiproliferative
effects of extracts and compounds from Ilex latifolia Thunb., a Chinese bitter
tea.
AB - Ilex latifolia Thunb., widely distributed in China, has been used as a functional
food and drunk for a long time. This study was aimed to identify the bioactive
constituents with antioxidant, antitumor, and anti-inflammatory properties. I.
latifolia was extracted with 95% ethanol and then partitioned into four
fractions: petroleum ether fraction, ethyl acetate fraction, n-butanol fraction,
and water fraction. Results showed that the ethyl acetate fraction was found to
have significant ferric reducing antioxidant power activity, DPPH radical
scavenging activity, and oxygen radical absorbance capacity, cytotoxicity against
human cervix carcinoma HeLa cells, and inhibitory effect on NO production in
macrophage RAW 264.7 cells. Five compounds were isolated from the ethyl acetate
fraction, and they were identified as ethyl caffeate (1), ursolic acid (2),
chlorogenic acid (3), 3,4-di-O-caffeoylquinic acid methyl ester (4), and 3,5-di-O
caffeoylquinic acid methyl ester (5), the last two of which were isolated for the
first time from I. latifolia. Compounds 4 and 5 exhibited cytotoxicity actions
against tumor cell line. Compound 3 showed the strongest anti-inflammatory
activity of all the compounds. The results obtained in this work might contribute
to the understanding of biological activities of I. latifolia and further
investigation on its potential application values for food and drug.
PMID- 25118955
TI - Images in Anesthesiology: Coexisting Aortic Stenosis and Left Ventricular Outflow
Tract Obstruction.
PMID- 25118954
TI - Spontaneous intracranial hypotension: presentation, diagnosis, and treatment.
PMID- 25118957
TI - Controlling the minimal self assembly of "complex" polyoxometalate clusters.
AB - Despite the vast number of polyoxometalate clusters now known, an ongoing and
important challenge is to understand causality in the assembly of "complex"
clusters at a mechanistic level, since this is the only way the rational,
targeted synthesis of new compounds will ever be achieved. Often, the complexity
of the reactions themselves makes such investigations near impossible, as very
small changes can often make dramatic differences. Herein, we explore a very
simple [A + B] binary synthetic system that gives rise to the facile assembly of
two isomeric anions, [Fe(III)(H2O)2{gamma-Fe(III)SiW9O34(H2O)}2](11-) (1) and
[Fe(III)(H2O)2{gamma-Fe(III)2SiW8O33(H2O)2}{gamma-SiW10O35}](11-) (2), which can
be formed as individual and dimeric species (3) and (4). Furthermore, the simple
binary nature of this synthetic system allowed its investigation by a
comprehensive time-resolved ESI-MS analysis, yielding unprecedented mechanistic
information regarding the initial interactions and reorganizations of the {gamma
SiW10} precursor in the presence of Fe(2+).
PMID- 25118956
TI - Synergetic effect of Zn substitution on the electron and phonon transport in
Mg2Si0.5Sn0.5-based thermoelectric materials.
AB - Mg2Si1-xSnx alloys are a prospective material for thermoelectric generators at
moderate temperatures. The thermoelectric properties of Mg2Si0.5Sn0.5-based
thermoelectric materials with only Zn substitution or Zn/Sb co-doping were
investigated. Isoelectronic Zn substitution did not affect the carrier
concentration, but improved the carrier mobility. Zn atoms incorporated into a Sb
doped Mg2Si0.5Sn0.5 matrix simultaneously boosted the power factor and suppressed
the lattice thermal conductivity, leading to an enhancement of the thermoelectric
figure of merit ZT of the resulting bulk materials. The interplay between the
electron and phonon transport of Mg2Si0.5Sn0.49Sb0.01 substituted with Zn at Mg
sites results in an enhancement of the ZT by 25% at ~730 K, from ZT~ 0.8 in
Mg2Si0.5Sn0.49Sb0.01 to ZT~ 1.0 in Mg1.98Zn0.02Si0.5Sn0.49Sb0.01. Solid solutions
in the Mg2Si-Mg2Sn system appear to be more promising for thermoelectric
applications.
PMID- 25118958
TI - Label-free single cell kinetics of the invasion of spheroidal colon cancer cells
through 3D Matrigel.
AB - This article reports label-free, real-time, and single-cell quantification of the
invasion of spheroidal colon cancer cells through three-dimensional (3D) Matrigel
using a resonant waveguide grating (RWG) imager. This imager employs a time
resolved swept wavelength interrogation scheme to monitor cell invasion and
adhesion with a temporal resolution up to 3 s and a spatial resolution of 12 MUm.
As the model system, spheroids of human colorectal adenocarcinoma HT-29 cells are
generated by culturing the cells in 96-well round-bottom ultralow attachment
plates. 3D Matrigel is formed by its gelation in 384-well RWG biosensor
microplates. The invasion and adhesion of spheroidal HT29 cells is initiated by
placing individual spheroids onto the Matrigel-coated biosensors. The time series
RWG images are obtained and used to extract the optical signatures arising from
the adhesion after the cells are dissociated from the spheroids and invade
through the 3D Matrigel. Compound profiling shows that epidermal growth factor
accelerates cancer cell invasion, while vandetanib, a multitarget kinase
inhibitor, dose-dependently inhibits invasion. This study demonstrates that the
label-free imager can monitor in real-time the invasion of spheroidal cancer
cells through 3D matrices.
PMID- 25118959
TI - Zn(II)-benzotriazolate clusters based amide functionalized porous coordination
polymers with high CO2 adsorption selectivity.
AB - Two new porous coordination polymers (PCPs) based on different nanosized C3
symmetry ligands and Zn(II)-benzotriazolate clusters have been synthesized
solvothermally. Both of the desolvated complexes show selective uptake of CO2
over CH4 and N2 at ambient temperature.
PMID- 25118960
TI - Facile formation of ordered vertical arrays by droplet evaporation of Au nanorod
organic solutions.
AB - Droplet evaporation is a simple method to induce organization of Au nanorods into
ordered superstructures. In general, the self-assembly process occurs by
evaporation of aqueous suspensions under strictly controlled experimental
conditions. Here we present formation of large area ordered vertical arrays by
droplet evaporation of Au nanorod organic suspensions. The uncontrolled (free
air) evaporation of such suspensions yielded to formation of ordered nanorod
domains covering the entire area of a 5 mm diameter droplet. Detailed
investigation of the process revealed that nanorods organized into highly ordered
vertical domains at the interface between solvent and air on a fast time scale
(minutes). The self-assembly process mainly depended on the initial concentration
of nanorod solution and required minimal control of other experimental
parameters. Nanorod arrays displayed distinct optical properties which were
analyzed by optical imaging and spectroscopy and compared to results obtained
from theoretical calculations. The potential use of synthesized arrays as surface
enhanced Raman scattering probes was demonstrated with the model molecule 4
aminobenzenthiol.
PMID- 25118961
TI - Selective peptide modifications via ruthenium-catalyzed allylic alkylations.
AB - Ruthenium-catalyzed allylic alkylations are an interesting alternative to
palladium-catalyzed processes, since they can provide products which are not
accessible under Pd-catalysis. Chiral terminal allylic substrates can be reacted
with perfect stereo- and regioretention, and also (Z)-configured allylic
substrates can be converted isomerization-free. This allows highly
stereoselective modifications of peptides at glycine subunits. The configuration
at the alpha-position of the new generated alpha-amino acid can be controlled by
the chiral peptide chain, and at the beta-position by using chiral allylic
substrates.
PMID- 25118963
TI - Management of sexually transmitted infections in New York State health care
organizations: who is thinking about the quality of STI care?
AB - BACKGROUND: Rising rates of sexually transmitted infections (STIs) warrant a
renewed focus on the management of STIs in health care organizations. The extent
to which hospitals and community health centers (CHCs) have established processes
and allocated staff for the management of STIs within their organizations remains
poorly understood. METHODS: A New York State Department of Health survey was
distributed electronically through a closed state communication network to
targeted administrators at New York State hospitals and CHCs. The survey asked if
STI management in their facilities included the following: the ability to measure
and report rates of STIs, a process to assess the quality of STI care and
treatment outcomes, and a centralized person/unit to coordinate its work
throughout the facility. Multivariate analysis was performed to identify whether
organizational characteristics were associated with survey findings. RESULTS:
Ninety-five percent (243/256) of hospitals and CHCs responded to the survey.
Fifty percent of respondents had a person or unit to report rates of STIs; 30%
reported an organization-wide process for monitoring the quality of STI care,
which, according to the multivariate analysis, was associated with CHCs; only 23%
reported having a centralized person or unit for coordinating STI management.
CONCLUSIONS: Most facilities report STI cases to comply with public health
surveillance requirements but do not measure infection rates, assess the quality
of STI care, or coordinate its work throughout the facility. The development of
this organizational capacity would likely decrease STI rates, improve treatment
outcomes, and address local public health goals.
PMID- 25118964
TI - A self-assessed questionnaire can help in the diagnosis of pelvic inflammatory
disease.
AB - BACKGROUND: Pelvic inflammatory disease (PID) is often responsible for acute
pelvic pain, yet its clinical diagnosis is difficult. The aim of this study was
to develop and validate prediction rules for the diagnosis of PID in patients
seen for acute pelvic pain, based solely on a self-assessed questionnaire.
METHODS: From September 2006 to April 2008, 499 consecutive patients presenting
at the gynecology emergency departments of 5 hospitals for acute pelvic pain
completed a Self-Assessment Questionnaire for Gynecological Emergencies. Seventy
three were identified as having a PID. Two-thirds of the database was randomly
selected for the derivation of the prediction rules, and the other third was used
for internal validation. We developed 2 scores, one that rules out a diagnosis of
PID and one that predicts PID, based on multiple logistic regression with
jackknife estimates. These scores were then validated with the validation data
set. RESULTS: Four variables were independently associated with PID: scattered
pain radiation and/or diffuse pain, insidious pain, peritoneal irritation, and
abnormal vaginal discharge. They were used to create a sensitive prediction model
that rules out PID. Four other variables were used to build another model that
predicted PID with high specificity: abnormal vaginal discharge, bilateral pelvic
pain, constipation, and presence of an intrauterine device. The probability of
PID for the patients in the low-risk group was 1.1% (95% confidence interval,
0.03-5.8), and the probability of PID in the high-risk group was 55% (95%
confidence interval, 31.5-76.9). CONCLUSION: These 2 prediction rules that
classify patients in low risk or high risk of PID, based on simple items
collected by a self-assessed questionnaire that are composed only of case history
and autodescription of the pain, may prove useful for diagnosing or ruling out
PID in patients with acute pelvic pain.
PMID- 25118962
TI - Effects of two Chinese herbal formulae for the treatment of moderate to severe
stable chronic obstructive pulmonary disease: a multicenter, double-blind,
randomized controlled trial.
AB - OBJECTIVE: The study aims to evaluate the efficacy and safety of two Chinese
herbal formulae for the treatment of stable COPD. METHODS: A multicenter, double
blind, double-dummy, and randomized controlled trial (RCT) was conducted. All
groups were treated with additional conventional medicines. There were a 6-month
treatment and a 12-month follow-up for 5 times. Primary outcomes included lung
function test, exacerbation frequency, score of SGRQ. Second outcomes consisted
of 6MWD, BODE index, psychological field score, inflammatory factors and
cortisol. RESULTS: A total of 331 patients were randomly divided into two active
treatment groups (Bushen Yiqi (BY) granule group, n = 109; Bushen Fangchuan (BF)
tablet group, n = 109) and a placebo group (n = 113). Finally 262 patients
completed the study. BY granule & BF tablet increased the values of VC, FEV1 (%)
and FEV1/FVC (%), compared with placebo. BY granule improved PEF. Both treatments
reduced acute exacerbation frequency (P = 0.067), BODE index and psychological
field score, while improved 6MWD. In terms of descent rang of SGRQ score, both
treatments increased (P = 0.01). Both treatments decreased inflammatory
cytokines, such as IL-8, and IL-17(P = 0.0219). BY granule obviously descended IL
17(P<0.05), IL-1beta (P = 0.05), IL-6, compared with placebo. They improved the
level of IL-10 and cortisol. BY granule raised cortisol (P = 0.07) and decreased
TNF-alpha. Both treatments slightly descended TGF-beta1. In terms of safety,
subject compliance and drug combination, there were no differences (P>0.05) among
three groups. CONCLUSIONS: BY granule and BF tablet were positively effective for
the treatment of COPD, and the former performed better in general. TRIAL
REGISTRATION: Chinese Clinical Trial Register center ChiCTR-TRC-09000530.
PMID- 25118965
TI - Bone involvement in secondary syphilis: a case report and systematic review of
the literature.
AB - Bone involvement is an unusual manifestation of secondary syphilis, but little
information is available in the English-language literature. We carried out a
systematic review of the English-language literature from 1964 to 2013,
describing cases of secondary syphilis with bone involvement. We also describe a
case of secondary syphilis with multiple osteolytic lesions, mimicking metastatic
cancer or myeloma, which was included in an analysis of 37 eligible cases of
secondary syphilis with bone involvement. Of these 37 patients, 28 (76%) patients
were male, and the median age was 32 years (range, 12-64 years). Eleven (30%)
patients had human immunodeficiency virus (HIV) infection with a median CD4
lymphocyte count of 343 cells/mm (range, 130-689 cells/mm). The diagnosis of
early syphilis was suspected based on mucocutaneous findings in 28 (76%) cases.
In the remaining 9 (24%) cases, high titers of nontreponemal serologic tests were
the only evidence of early syphilis. The median venereal disease research
laboratory (VDRL) titer was 1:64 (range, 1:8-1:320), and median rapid plasma
reagin (RPR) titer was 1:64 (range, 1:16-1:512). The bones most often affected
were long bones of the limbs (n = 22) and skull (n = 21). The bone lesions were
multifocal in 27 (73%) cases and osteolytic in 19 (51%) cases. The treatment of
syphilitic bone lesions was medical only in most patients, and prognosis was
favorable with high-dose penicillin therapy. Clinical features and outcome
between HIV-uninfected and HIV-infected patients were not different. Knowledge of
this rare entity may lead to early diagnosis and appropriate management.
PMID- 25118966
TI - Chlamydia screening for sexually active young women under the Affordable Care
Act: new opportunities and lingering barriers.
AB - The Affordable Care Act of 2010 (ACA) contains a provision requiring private
insurers issuing or renewing plans on or after September 23, 2010, to provide,
without cost sharing, preventive services recommended by US Preventive Services
Task Force (grades A and B), among other recommending bodies. As a grade A
recommendation, chlamydia screening for sexually active young women 24 years and
younger and older women at risk for chlamydia falls under this requirement. This
article examines the potential effect on chlamydia screening among this
population across private and public health plans and identifies lingering
barriers not addressed by this legislation. Examination of the impact on women
with private insurance touches upon the distinction between coverage under
grandfathered plans, where the requirement does not apply, and nongrandfathered
plans, where the requirement does apply. Acquisition of private health insurance
through health insurance Marketplaces is also discussed. For public health plans,
coverage of preventive services without cost sharing differs for individuals
enrolled in standard Medicaid, covered under the Medicaid expansion included in
the ACA, or those enrolled under the Children's Health Insurance Program or who
fall under Early, Periodic, Screening, Diagnosis and Treatment criteria. The
discussion of lingering barriers not addressed by the ACA includes the uninsured,
physician reimbursement, cost sharing, confidentiality, low rates of appropriate
sexual history taking by providers, and disclosures of sensitive information. In
addition, the role of safety net programs that provide health care to individuals
regardless of ability to pay is examined in light of the expectation that they
also remain a payer of last resort.
PMID- 25118968
TI - Molecular typing of Treponema pallidum: identification of a new sequence of
tp0548 gene in Shandong, China.
PMID- 25118967
TI - The cost of implementing rapid HIV testing in sexually transmitted disease
clinics in the United States.
AB - INTRODUCTION: Rapid HIV testing in high-risk populations can increase the number
of persons who learn their HIV status and avoid spending clinic resources to
locate persons identified as HIV infected. METHODS: We determined the cost to
sexually transmitted disease (STD) clinics of point-of-care rapid HIV testing
using data from 7 public clinics that participated in a randomized trial of rapid
testing with and without brief patient-centered risk reduction counseling in
2010. Costs included counselor and trainer time, supplies, and clinic overhead.
We applied national labor rates and test costs. We calculated median clinic start
up costs and mean cost per patient tested, and projected incremental annual costs
of implementing universal rapid HIV testing compared with current testing
practices. RESULTS: Criteria for offering rapid HIV testing and methods for
delivering nonrapid test results varied among clinics before the trial. Rapid HIV
testing cost an average of US $22/patient without brief risk reduction counseling
and US $46/patient with counseling in these 7 clinics. Median start-up costs per
clinic were US $1100 and US $16,100 without and with counseling, respectively.
Estimated incremental annual costs per clinic of implementing universal rapid HIV
testing varied by whether or not brief counseling is conducted and by current
clinic testing practices, ranging from a savings of US $19,500 to a cost of US
$40,700 without counseling and a cost of US $98,000 to US $153,900 with
counseling. CONCLUSIONS: Universal rapid HIV testing in STD clinics with same-day
results can be implemented at relatively low cost to STD clinics, if brief risk
reduction counseling is not offered.
PMID- 25118969
TI - The molecular typing data of recently identified subtype 11q/j of Treponema
pallidum subsp. pallidum suggest imported case of yaws.
PMID- 25118970
TI - When is syphilis not syphilis? Or is it?
PMID- 25118971
TI - Age-specific chlamydial infection among pregnant women in the United States:
evidence for updated recommendations.
AB - BACKGROUND: In the United States, chlamydia screening has been recommended for
all pregnant women by the Centers for Disease Control and Prevention (CDC) but
only for pregnant women who are at increased risk by the US Preventive Services
Task Force (USPSTF). Very limited evidence, such as age-specific chlamydia
positivity in pregnant women, has been used to develop these recommendations.
METHODS: We analyzed data from a large commercial laboratory corporation in the
United States in 2013. At the first prenatal visit made by women aged 15 to 44
years for whom a chlamydia test was performed between June 2008 and July 2010, we
estimated positivity of chlamydia by age, insurance coverage, geographic region,
and test type. RESULTS: Of 601,001 pregnant women aged 15 to 44 years who had
routine prenatal care, 62.9% had private insurance and 32.9% had Medicaid
coverage, 60.3% resided in the South region, and 43.2% were aged 15 to 24 years,
26.8% were aged 25 to 29 years, and 19.1% were aged 30 to 34 years. Chlamydia
positivity was 3.6% overall, and significantly decreased as age increased (15-19
years: 9.6 %; 20-24 years: 5.2%; 25-29 years: 1.8%; 30-34 years: 0.9%; and 35-44
years: 0.6%; P < 0.05). CONCLUSIONS: Our findings of higher positivity among
younger pregnant women suggest that the yield is likely to be greater from
screening younger pregnant women than from screening older pregnant women to
identify chlamydia infection. The benefits of harmonizing CDC and USPSTF
recommendations for pregnant women could be explored by reviewing age-specific
positivity data and estimating the frequency of prenatal adverse health outcomes
caused by chlamydia to develop consensus regarding the age limit for pregnant
women who should be screened.
PMID- 25118972
TI - Congenital syphilis investigation processes and timing in Louisiana.
AB - BACKGROUND: Congenital syphilis (CS) is a potentially life-threatening yet
preventable infection. State and local public health jurisdictions conduct
investigations of possible CS cases to determine case status and to inform public
health prevention efforts. These investigations occur when jurisdictions receive
positive syphilis test results from pregnant women or from infants. METHODS: We
extracted data from Louisiana's electronic case management system for 328 infants
investigated as possible CS cases in 2010 to 2011. Using date stamps from the
case management system, we described CS investigations in terms of processes and
timing. RESULTS: Eighty-seven investigations were prompted by positive test
results from women who were known to be pregnant by the health jurisdiction, and
241 investigations were prompted by positive syphilis test results from infants.
Overall, investigations required a median of 101 days to complete, although 25%
were complete within 36 days. Investigations prompted by positive test results
from infants required a median of 135 days to complete, and those prompted by
positive test results from pregnant women required a median of 41 days.
CONCLUSIONS: Three times as many CS investigations began with reported positive
syphilis test results from infants as from pregnant women, and these
investigations required more time to complete. When CS investigations begin after
an infant's birth, the opportunity to ensure that women are treated during
pregnancy is missed, and surveillance data cannot inform prevention efforts on a
timely basis. Consistently ascertaining pregnancy status among women whose
positive syphilis test results are reported to public health jurisdictions could
help to assure timely CS prevention efforts.
PMID- 25118973
TI - Cross-sectional study of genital, rectal, and pharyngeal Chlamydia and gonorrhea
in women in rural South Africa.
AB - BACKGROUND: Epidemiological data of genital chlamydia and gonorrhea, required to
inform design and implementation of control programs, are limited for rural
Africa. There are no data on the prevalence of rectal or pharyngeal infections
among African women. METHODS: A cross-sectional study of 604 adult women visiting
25 primary health care facilities in rural South Africa was conducted. Vaginal,
anorectal, and oropharyngeal swabs were tested for Chlamydia trachomatis and
Neisseria gonorrhoeae. RESULTS: Prevalence of genital chlamydia was 16% and that
of gonorrhea was 10%; rectal chlamydial infection was diagnosed in 7.1% and
gonococcal in 2.5% of women. One woman had pharyngeal chlamydia. Most women with
genital chlamydia (61%) and gonorrhea (57%) were asymptomatic. Independent risk
factors for genital chlamydia were younger age (adjusted odds ratio [aOR], 0.96
per year; 95% confidence interval [CI], 0.93-0.98), hormonal contraceptive use
(aOR, 2.2; 95% CI, 1.3-3.7), pregnancy (aOR, 2.4; 95% CI, 1.3-4.4), and
intravaginal cleansing (aOR, 1.7; 95% CI, 1.04-2.8). Intravaginal cleansing was
associated with genital gonorrhea (aOR, 1.9; 95% CI, 1.1-3.3). CONCLUSIONS:
Genital and rectal, but not pharyngeal, chlamydia and gonorrhea are highly
prevalent and frequently asymptomatic in women in rural South Africa. Young women
attending health care facilities for antenatal care or family planning should be
prioritized in control efforts.
PMID- 25118974
TI - Flexible graphene-graphene composites of superior thermal and electrical
transport properties.
AB - Graphene is known for high thermal and electrical conductivities. In the
preparation of neat carbon materials based on graphene, a common approach has
been the use of well-exfoliated graphene oxides (GOs) as the precursor, followed
by conversion to reduced GOs (rGOs). However, rGOs are more suitable for the
targeted high electrical conductivity achievable through percolation but
considerably less effective in terms of efficient thermal transport dictated by
phonon progression. In this work, neat carbon films were fabricated directly from
few-layer graphene sheets, avoiding rGOs completely. These essentially graphene
graphene composites were of a metal-like appearance and mechanically flexible,
exhibiting superior thermal and electrical transport properties. The observed
thermal and electrical conductivities are higher than 220 W/m . K and 85000 S/m,
respectively. Some issues in the further development of these mechanically
flexible graphene-graphene nanocomposite materials are discussed and so are the
associated opportunities.
PMID- 25118975
TI - Enhancing Patient Flexibility of Subcutaneous Immunoglobulin G Dosing:
Pharmacokinetic Outcomes of Various Maintenance and Loading Regimens in the
Treatment of Primary Immunodeficiency.
AB - INTRODUCTION: Standard treatment for patients with primary immunodeficiency (PID)
is monthly intravenous immunoglobulin (IVIG), or weekly/biweekly subcutaneous
immunoglobulin (SCIG) infusion. We used population pharmacokinetic modeling to
predict immunoglobulin G (IgG) exposure following a broad range of SCIG dosing
regimens for initiation and maintenance therapy in patients with PID. METHODS:
Simulations of SCIG dosing were performed to predict IgG concentration-time
profiles and exposure metrics [steady-state area under the IgG concentration-time
curve (AUC), IgG peak concentration (C max), and IgG trough concentration (C min)
ratios] for various infusion regimens. RESULTS: The equivalent of a weekly SCIG
maintenance dose administered one, two, three, five, or seven times per week, or
biweekly produced overlapping steady-state concentration-time profiles and
similar AUC, C max, and C min values [95% confidence interval (CI) for ratios was
0.98-1.03, 0.95-1.09, and 0.92-1.08, respectively]. Administration every 3 or 4
weeks resulted in higher peaks and lower troughs; the 95% CI of the AUC, C max,
and C min ratios was 0.97-1.04, 1.07-1.26, and 0.86-0.95, respectively. IgG
levels >7 g/L were reached within 1 week using a loading dose regimen in which
the weekly maintenance dose was administered five times in the first week of
treatment. In patients with very low endogenous IgG levels, administering 1.5
times the weekly maintenance dose five times in the first week of treatment
resulted in a similar response. CONCLUSIONS: The same total weekly SCIG dose can
be administered at different intervals, from daily to biweekly, with minimal
impact on serum IgG levels. Several SCIG loading regimens rapidly achieve
adequate serum IgG levels in treatment-naive patients.
PMID- 25118977
TI - Composition-dependent interfacial abruptness in Au-catalyzed Si(1-x)Ge(x)/Si/Si(1
x)Ge(x) nanowire heterostructures.
AB - As MOSFETs are scaled down, power dissipation remains the most challenging
bottleneck for nanoelectronic devices. To circumvent this challenge, alternative
devices such as tunnel field effect transistors are potential candidates, where
the carriers are injected by a much less energetically costly quantum band to
band tunneling mechanism. In this context, axial nanowire heterointerfaces with
well-controlled interfacial abruptness offer an ideal structure. We demonstrate
here the effect of tuning the Ge concentration in a Si1-xGex part of the nanowire
on the Si/Si1-xGex and Si1-xGex/Si interfacial abruptness in axial Si-Si1-xGex
nanowire heterostructures grown by the Au-catalyzed vapor-liquid-solid method.
The two heterointerfaces are always asymmetric irrespective of the Ge
concentration or nanowire diameter. For a fixed diameter, the value of interface
abruptness decreases with increasing the Ge content for the Si/Si1-xGex interface
but shows no strong Ge dependence at the Si1-xGex/Si interface where it features
a linear correlation with the nanowire diameter. To rationalize these findings, a
kinetic model for the layer-by-layer growth of nanowire heterostructures from a
ternary Au-Ge-Si alloy is established that predicts a discrepancy in Ge
concentration in the layer and the catalyst droplet. The Ge concentration in each
layer is predicted to be dependent on the composition of the preceding layer. The
most abrupt heterointerface (~5 nm) is achieved by growing Si1-xGex with x = 0.85
on Si in a 25 nm diameter nanowire.
PMID- 25118976
TI - Medically complex pregnancies and early breastfeeding behaviors: a retrospective
analysis.
AB - BACKGROUND: Breastfeeding is beneficial for women and infants, and medical
contraindications are rare. Prenatal and labor-related complications may hinder
breastfeeding, but supportive hospital practices may encourage women who intend
to breastfeed. We measured the relationship between having a complex pregnancy
(entering pregnancy with hypertension, diabetes, or obesity) and early infant
feeding, accounting for breastfeeding intentions and supportive hospital
practices. METHODS: We performed a retrospective analysis of data from a
nationally-representative survey of women who gave birth in 2011-2012 in a US
hospital (N = 2400). We used logistic regression to examine the relationship
between pregnancy complexity and breastfeeding. Self-reported prepregnancy
diabetes or hypertension, gestational diabetes, or obesity indicated a complex
pregnancy. The outcome was feeding status 1 week postpartum; any breastfeeding
was evaluated among women intending to breastfeed (N = 1990), and exclusive
breastfeeding among women who intended to exclusively breastfeed (N = 1418). We
also tested whether breastfeeding intentions or supportive hospital practices
mediated the relationship between pregnancy complexity and infant feeding status.
RESULTS: More than 33% of women had a complex pregnancy; these women had 30%
lower odds of intending to breastfeed (AOR = 0.71; 95% CI, 0.52-0.98). Rates of
intention to exclusively breastfeed were similar for women with and without
complex pregnancies. Women who intended to breastfeed had similar rates of any
breastfeeding 1 week postpartum regardless of pregnancy complexity, but
complexity was associated with >30% lower odds of exclusive breastfeeding 1 week
among women who intended to exclusively breastfeed (AOR = 0.68; 95% CI, 0.47
0.98). Supportive hospital practices were strongly associated with higher odds of
any or exclusive breastfeeding 1 week postpartum (AOR = 4.03; 95% CI, 1.81-8.94;
and AOR = 2.68; 95% CI, 1.70-4.23, respectively). CONCLUSIONS: Improving clinical
and hospital support for women with complex pregnancies may increase
breastfeeding rates and the benefits of breastfeeding for women and infants.
PMID- 25118979
TI - Normal controlled attenuation parameter values: a prospective study of healthy
subjects undergoing health checkups and liver donors in Korea.
AB - BACKGROUND/AIMS: The controlled attenuation parameter (CAP) is a noninvasive
method of assessing hepatic steatosis. We defined the normal range of CAP values
in healthy subjects and evaluated the associated factors. METHODS: CAP values
were measured in a cohort of healthy subjects who were screened as living liver
transplantation donors and those who underwent health checkups. Subjects with
current or a history of chronic liver disease, abnormalities on liver-related
laboratory tests, or fatty liver on ultrasonography or biopsy were excluded.
RESULTS: The mean age of the 264 recruited subjects (131 males and 133 females;
76 potential liver donors and 188 subjects who had undergone health checkups) was
49.2 years. The mean CAP value was 224.8 +/- 38.7 dB/m (range 100.0-308.0 dB/m),
and the range of normal CAP values (5th-95th percentiles) was 156.0-287.8 dB/m.
The mean CAP value was significantly higher in the health checkup than in the
potential liver donor group (227.5 +/- 42.0 vs. 218.2 +/- 28.3 dB/m, P = 0.040).
CAP values did not differ significantly according to gender or age in either
group (all P > 0.05). In a multivariate linear regression analysis, body mass
index (beta = 0.271, P = 0.024) and triglyceride levels (beta = 0.348, P = 0.008)
were found to be independently associated with CAP values. CONCLUSION: We
determined the normal range of CAP values and found that body mass index and
triglyceride levels were associated with the CAP values of healthy subjects.
PMID- 25118981
TI - Carbon monoxide inhibits inward rectifier potassium channels in cardiomyocytes.
AB - Reperfusion-induced ventricular fibrillation (VF) severely threatens the lives of
post-myocardial infarction patients. Carbon monoxide (CO)--produced by haem
oxygenase in cardiomyocytes--has been reported to prevent VF through an unknown
mechanism of action. Here, we report that CO prolongs action potential duration
(APD) by inhibiting a subset of inward-rectifying potassium (Kir) channels. We
show that CO blocks Kir2.2 and Kir2.3 but not Kir2.1 channels in both
cardiomyocytes and HEK-293 cells transfected with Kir. CO directly inhibits
Kir2.3 by interfering with its interaction with the second messenger
phosphatidylinositol (4,5)-bisphosphate (PIP2). As the inhibition of Kir2.2 and
Kir2.3 by CO prolongs APD in myocytes, cardiac Kir2.2 and Kir2.3 are promising
targets for the prevention of reperfusion-induced VF.
PMID- 25118980
TI - The importance of intraoperative selenium blood levels on organ dysfunction in
patients undergoing off-pump cardiac surgery: a randomised controlled trial.
AB - INTRODUCTION: Cardiac surgery is accompanied by an increase of oxidative stress,
a significantly reduced antioxidant (AOX) capacity, postoperative inflammation,
all of which may promote the development of organ dysfunction and an increase in
mortality. Selenium is an essential co-factor of various antioxidant enzymes. We
hypothesized a less pronounced decrease of circulating selenium levels in
patients undergoing off-pump coronary artery bypass (OPCAB) surgery due to less
intraoperative oxidative stress. METHODS: In this prospective randomised,
interventional trial, 40 patients scheduled for elective coronary artery bypass
grafting were randomly assigned to undergo either on-pump or OPCAB-surgery, if
both techniques were feasible for the single patient. Clinical data, myocardial
damage assessed by myocard specific creatine kinase isoenzyme (CK-MB),
circulating whole blood levels of selenium, oxidative stress assessed by
asymmetric dimethylarginine (ADMA) levels, antioxidant capacity determined by
glutathionperoxidase (GPx) levels and perioperative inflammation represented by
interleukin-6 (IL-6) levels were measured at predefined perioperative time
points. RESULTS: At end of surgery, both groups showed a comparable decrease of
circulating selenium concentrations. Likewise, levels of oxidative stress and IL
6 were comparable in both groups. Selenium levels correlated with antioxidant
capacity (GPx: r = 0.720; p<0.001) and showed a negative correlation to
myocardial damage (CK-MB: r = -0.571, p<0.001). Low postoperative selenium
levels had a high predictive value for the occurrence of any postoperative
complication. CONCLUSIONS: OPCAB surgery is not associated with less oxidative
stress and a better preservation of the circulating selenium pool than on-pump
surgery. Low postoperative selenium levels are predictive for the development of
complications. TRIAL REGISTRATION: ClinicalTrials.gov NCT01409057.
PMID- 25118982
TI - Thermal effects of cold light sources used in otologic surgery.
AB - The objective of this study was to investigate the thermal effects of cold light
sources and endoscopes on the inner ear. 25 male guinea pigs were assigned
equally to five groups (1: Halogen-1 min, 2: Halogen-5 min, 3: Xenon-1 min, 4:
Xenon-5 min, 5: Controls). After both bullae of the guinea pigs were opened,
light sources and endoscopes were positioned in the middle ears of the first four
groups for specific time periods. DPOAE and ABR tests were conducted on all
animals at the beginning of the study, at the end of surgery, and 2 h after
surgery. The temperatures of cold light sources were measured by a thermocouple
thermometer, and the surface temperatures of the endoscopes were measured by an
infrared thermometer. DPOAE and ABR measurements performed right after and 2 h
after surgery in group 1, 2, 3, and 5 did not reveal any significant difference.
In group 4, DPOAE values were significantly lower and ABR threshold values were
significantly higher than those in the other groups, right after and 2 h after
surgery. Thermocouple thermometer readings showed that, after the first minute,
the Xenon light source generated significantly more temperature rise than the
Halogen light source. The surface temperatures of all endoscopes returned to
normal approximately 1 min after light sources were turned off. Our study
demonstrated that when an endoscope using a Xenon light source was applied to the
middle ear for a specific time periods, inner ear functions deteriorated, as
reflected by audiologic tests.
PMID- 25118983
TI - ABCB1 C3435T polymorphism and the risk of ischemic heart disease: a meta
analysis.
AB - ATP binding cassette transporter 1 (ABCB1) plays a critical role in the
development and progression of cardiovascular disease. Emerging evidence suggests
that common functional polymorphisms in the ABCB1 gene might have an impact on an
individual's susceptibility to ischemic heart disease, but individually published
results are inconclusive. The MEDLINE (1966-2013), the Cochrane Library Database
(Issue 12, 2013), EMBASE (1980-2013), CINAHL (1982-2013), Web of Science (1945
2013), and the Chinese Biomedical Database (CBM; 1982-2013) were searched without
language restrictions. Meta-analysis was performed with the use of the STATA
statistical software. Odds ratios (OR) with their 95% confidence intervals (95%
CIs) were calculated. Seven case-control studies with a total of 2310 myocardial
infarction (MI) patients and 10,506 acute coronary syndrome (ACS) patients met
the inclusion criteria. Our meta-analysis results indicated that ABCB1 C3435T
polymorphism may be associated with an increased risk of MI and ACS, especially
among Asian populations (T allele vs. C allele: OR=1.40, 95% CI=1.31-1.49,
ph=0.058). Meta-regression analyses showed that clinical subtype and ethnicity
may be the main sources of heterogeneity (T allele vs. C allele: OR=1.16, 95%
CI=0.97-1.37, ph=0.036). Our findings provide empirical evidence that ABCB1
C3435T polymorphism may contribute to the risk of MI and ACS, especially among
Caucasian populations. Thus, detection of ABCB1 C3435T polymorphism may be a
promising biomarker for the early detection of MI and ACS.
PMID- 25118985
TI - Titanosaur osteoderms from the Upper Cretaceous of Lo Hueco (Spain) and their
implications on the armor of Laurasian titanosaurs.
AB - Titanosaurs are the only sauropod dinosaurs known to bear a dermal armor. Their
osteoderms are relatively rare finds, with few more than a hundred specimens
recovered worldwide. Also, little is known about their intra-individual, intra
specific or inter-specific variability. The macrovertebrate site of Lo Hueco
(Upper Cretaceous; Cuenca, Spain) has yielded several complete specimens of
osteoderms, some associated with fairly articulated specimens. They are all
variations of the morphotype known as bulb and root. The presence of only this
morphotype in Europe, which is considered as the primitive condition among
titanosaurs, seems to indicate that the known Upper Cretaceous Laurasian
titanosaurs only bore these referred bulb and root osteoderms. An eliptic Fourier
analysis on the outline of complete specimens from this morphotype reveals: i)
that they truly are part of a morphological cline; and ii) the existence of a
consistent correlation between the outline and the morphology of the bulb. Such
variation along a cline is more consistent with intra-individual rather than
inter-specific variation. The osteoderms associated with a single titanosaur
individual from Lo Hueco reinforce this hypothesis.
PMID- 25118984
TI - The gut microbiota and developmental programming of the testis in mice.
AB - Nutrients and environmental chemicals, including endocrine disruptors, have been
incriminated in the current increase in male reproductive dysfunction, but the
underlying mechanisms remain unknown. The gastrointestinal tract represents the
largest surface area exposed to our environment and thereby plays a key role in
connection with exposure of internal organs to exogenous factors. In this context
the gut microbiome (all bacteria and their metabolites) have been shown to be
important contributors to body physiology including metabolism, cognitive
functions and immunity. Pivotal to male reproduction is a proper development of
the testis, including the formation of the blood-testis barrier (BTB) that
encapsulates and protects germ cells from stress induced environmental cues, e.g.
pathogenic organisms and xenobiotics. Here we used specific pathogen free (SPF)
mice and germ-free (GF) mice to explore whether gut microbiota and/or their
metabolites can influence testis development and regulation of BTB. Lumen
formation in the seminiferous tubules, which coincides with the development of
the BTB was delayed in the testes of GF mice at 16 days postpartum. In addition,
perfusion experiments (Evans blue) demonstrated increased BTB permeability in
these same mice. Reduced expressions of occludin, ZO-2 and E-cadherin in GF
testis suggested that the microbiota modulated BTB permeability by regulation of
cell-cell adhesion. Interestingly, exposure of GF mice to Clostridium
Tyrobutyricum (CBUT), which secrete high levels of butyrate, restored the
integrity of the BTB and normalized the levels of cell adhesion proteins.
Moreover, the GF mice exhibited lower serum levels of gonadotropins (LH and FSH)
than the SPF group. In addition, the intratesticular content of testosterone was
lower in GF compared to SPF or CBUT animals. Thus, the gut microbiome can
modulate the permeability of the BTB and might play a role in the regulation of
endocrine functions of the testis.
PMID- 25118987
TI - Effects of ambient temperature on the performance of CCD array spectroradiometers
and practical implications for field measurements.
AB - The performance of miniature CCD array spectroradiometers, which are widely used
for the assessment of personal and environmental exposures, may be affected by
variations in ambient temperature. The dark signal, spectral sensitivity and
wavelength position of six different array spectroradiometer models, produced by
two different manufacturers, were assessed in ambient temperatures ranging from 5
degrees C to 40 degrees C. The results are presented with a discussion of the
practical implications for field measurements when the instruments are used
outside of a temperature controlled environment.
PMID- 25118986
TI - A new basal ankylosaurid (Dinosauria: Ornithischia) from the Lower Cretaceous
Jiufotang Formation of Liaoning Province, China.
AB - A new ankylosaurid, Chuanqilong chaoyangensis gen. et sp. nov., is described here
based on a nearly complete skeleton from the Lower Cretaceous Jiufotang Formation
of Baishizui Village, Lingyuan City, Liaoning Province, China. Chuanqilong
chaoyangensis can be diagnosed on the basis of two autapomorphies (glenoid fossa
for quadrate at same level as the dentary tooth row; distally tapering ischium
with constricted midshaft) and also a unique combination of character states
(slender, wedge-like lacrimal; long retroarticular process; humerus with strongly
expanded proximal end; ratio of humerus to femur length = 0.88). Although a
phylogenetic analysis places Chuanqilong chaoyangensis as the sister taxon of the
sympatric Liaoningosaurus near the base of the Ankylosauridae, the two taxa can
be distinguished on the basis of many features, such as tooth morphology and
ischial shape, which are not ontogeny-related. Chuanqilong chaoyangensis
represents the fourth ankylosaurid species reported from the Cretaceous of
Liaoning, China, suggesting a relatively high diversity in Cretaceous Liaoning.
PMID- 25118988
TI - Through a glass darkly: economics and personalised medicine.
AB - Personalised medicine and pharmacogenetic-test-guided treatment strategies will
be of increasing importance in the future, both in terms of healthcare provision
and evaluation. It is well recognised that significant variability exists in the
response of patients to drugs resulting from genetic or biological variations;
however, we are only now gradually becoming aware of the complexities involved.
Enormous variability occurs in the risk-benefit ratio that will be experienced by
each individual patient as a consequence of their overall genetic make-up.
Although not a panacea, enhanced scientific knowledge of the genetic basis for
such variability offers the potential for a more 'tailored' approach to
prescribing in the future, making it more closely attuned to the needs of the
individual patient. Such 'personalised' medicine has the potential to
revolutionise care provision in a manner that provides a range of challenges to
current structures and processes of 'conventional' healthcare delivery. The aim
of this paper is to outline such challenges and analyse potential ways in which
they may be addressed in the future. It provides non-expert readers with a non
technical case study of the complexities inherent in the evaluation of a
pharmacogenetic-test-guided treatment strategy from a health economic
perspective. Wherever possible, technical issues have been minimised; however,
references are provided for readers who wish to enhance their knowledge of the
pharmacological basis of the case study of cytochrome P450 test-guided treatment.
The case study aims simply to illustrate the approach and difficulties
encountered in the health economic evaluation of complex pharmacogenetic
technologies. Such technologies present a range of new and complex issues which
have crucial implications for health economists attempting to obtain an accurate
assessment of the 'value' of the technology in clinical practice in an array of
patient subgroups. Personalised medicine is the future and this paper highlights
how pharmaceutical manufacturers, clinicians, regulators and other stakeholders
must all play their part in the inevitable and accelerating move into this
complex and uncertain future.
PMID- 25118989
TI - A review of approaches for the management of specialty pharmaceuticals in the
United States.
AB - With increased innovation and development of specialty pharmaceuticals, the US
and global healthcare industries are looking to implement appropriate management
strategies to control both utilization and costs. Specialty pharmaceuticals are
high-cost medications that treat complex, chronic, rare, and difficult-to-manage
conditions. These drugs require special drug handling, appropriate clinical
outcomes monitoring, and effective cost controls. The primary scope of this
article is to discuss various strategies being implemented for specialty
pharmaceutical utilization and cost management and correlated outcomes in the
USA; these outcomes include enhanced health insurance plan benefit designs with
formulary modifications and greater patient cost burden. Additional methods to
manage specialty pharmaceuticals include the use of specialty pharmacies for drug
distribution, increased emphasis on coordination of care and evidence-based
medicine, as well as healthcare reform and regulations. Healthcare spending, both
in the US and globally, continues to increase, with a rising proportion of drug
spend towards specialty pharmaceuticals. Continued specialty pharmaceutical
innovation and introduction of biosimilar products will evolve the currently
utilized management strategies for these drugs.
PMID- 25118992
TI - Treatment and management of neuromuscular channelopathies.
AB - OPINION STATEMENT: Neuromuscular channelopathies are heterogeneous disorders with
marked phenotypic and genotypic variability. These include non-dystrophic
myotonia (NDM), periodic paralysis (PP), and congenital myasthenic syndrome
(CMS). Their diverse clinical manifestations remain a challenge in diagnosis and
management to this date. These disorders impact quality of life and cause
lifelong disabling symptoms. Treatment options are few and not FDA-approved. This
is largely due to a paucity of large, randomized clinical trials in these rare
diseases. Challenges of conducting such trials include the rarity of these
disorders and the genetic heterogeneity. Physicians rely on off-label use of
drugs to treat muscle channelopathies to reduce morbidity and improve quality of
life. Besides pharmacological treatment, dietary modifications, lifestyle
changes, awareness of triggers, and genetic counseling also play an important
role in long-term disease management. This article reviews the current management
strategies for neuromuscular channelopathies.
PMID- 25118991
TI - Identification of the conserved and novel miRNAs in Mulberry by high-throughput
sequencing.
AB - miRNAs are a class of non-coding endogenous small RNAs. They play vital roles in
plant growth, development, and response to biotic and abiotic stress by
negatively regulating genes. Mulberry trees are economically important species
with multiple uses. However, to date, little is known about mulberry miRNAs and
their target genes. In the present study, three small mulberry RNA libraries were
constructed and sequenced using high-throughput sequencing technology. Results
showed 85 conserved miRNAs belonging to 31 miRNA families and 262 novel miRNAs at
371 loci. Quantitative real-time PCR (qRT-PCR) analysis confirmed the expression
pattern of 9 conserved and 5 novel miRNAs in leaves, bark, and male flowers. A
total of 332 potential target genes were predicted to be associated with these
113 novel miRNAs. These results provide a basis for further understanding of
mulberry miRNAs and the biological processes in which they are involved.
PMID- 25118993
TI - Downregulated CXCL12 expression in mesenchymal stem cells associated with severe
aplastic anemia in children.
AB - The mechanisms of idiopathic severe aplastic anemia (SAA) in children are not
completely understood. Insufficiency of the bone marrow microenvironment, in
which mesenchymal stem cells (MSCs) are an important element, can be a potential
factor associated with hematopoietic impairment. In the current study, we studied
whether aberrant gene expression could be found in MSCs from children with SAA.
Using microarray analysis, two different patterns of global gene expression were
detected in the SAA MSCs. Fourteen genes (POLE2, HGF, KIF20A, TK1, IL18R1, KITLG,
FGF18, RRM2, TTK, CXCL12, DLG7, TOP2A, NUF2, and TYMS), which are related to DNA
synthesis, cytokines, or growth factors, were significantly downregulated.
Further, knockdown of gene expression was performed using the small hairpin RNA
(shRNA)-containing lentivirus method. We found that knockdown of CXCL12, HGF, IL
18R1, FGF18, or RRM2 expression compelled MSCs from the controls to behave like
those from the SAA children, with decreased survival and differentiation
potential. Among them, inhibition of CXCL12 gene expression had the most profound
effects on the behavior of MSCs. Further experiments regarding re-introduction of
the CXCL12 gene could largely recover the survival and differentiation potential
in MSCs with inhibition of CXCL12 expression. Our findings suggest that MSCs from
children with SAA exhibit aberrant gene expression profiles and downregulation of
CXCL12 gene may be associated with alterations in the bone marrow
microenvironment.
PMID- 25118994
TI - CD4+ T cell counts reflect the immunosuppressive state of CD4 helper cells in
patients after allogeneic stem cell transplantation.
AB - The recovery of the host immune system after allogeneic hematopoietic stem cell
transplantation is pivotal to prevent infections, relapse, and secondary
malignancies. In particular, numerical CD4+ T cells reconstitution is delayed and
CD4 helper cell function is considered impaired as a consequence of the
transplant procedure and concomitant immunosuppressive medication. From HIV/AIDS
patients, it is known that numerical and functional CD4 defects increase the risk
of opportunistic infections. However, and in contrast to patients with HIV, anti
infective prophylaxis after allogeneic transplantation is usually given for 6
months depending on immunosuppressive medication and existing graft-versus-host
disease but independently of absolute CD4+ T cells counts. We hypothesized that a
qualitative T cell defect is existing after allogeneic transplantation,
especially in patients with delayed immune-reconstitution. Applying
transcriptional as well as functional approaches, we show that CD4+ T cells with
delayed recovery have a distinct transcriptional profile and cluster differently
from T cells originated from patients with completed immune recovery. Moreover,
inhibitory signatures are substantially enriched within the transcriptional
profile of these T cells translating to functional defects and impaired
interleukin 2 production. In addition to time after transplant, CD4+ T cells
numbers should be considered for the decision to stop or maintain antimicrobial
prophylaxis in patients after allogeneic stem cell transplantation.
PMID- 25118990
TI - Functional interaction between bicarbonate transporters and carbonic anhydrase
modulates lactate uptake into mouse cardiomyocytes.
AB - Blood-derived lactate is a precious energy substrate for the heart muscle.
Lactate is transported into cardiomyocytes via monocarboxylate transporters
(MCTs) together with H(+), which couples lactate uptake to cellular pH
regulation. In this study, we have investigated how the interplay between
different acid/base transporters and carbonic anhydrases (CA), which catalyze the
reversible hydration of CO2, modulates the uptake of lactate into isolated mouse
cardiomyocytes. Lactate transport was estimated both as lactate-induced
acidification and as changes in intracellular lactate levels measured with a
newly developed Forster resonance energy transfer (FRET) nanosensor. Recordings
of intracellular pH showed an increase in the rate of lactate-induced
acidification when CA was inhibited by 6-ethoxy-2-benzothiazolesulfonamide (EZA),
while direct measurements of lactate flux demonstrated a decrease in MCT
transport activity, when CA was inhibited. The data indicate that catalytic
activity of extracellular CA increases lactate uptake and counteracts
intracellular lactate-induced acidification. We propose a hypothetical model, in
which HCO3 (-), formed from cell-derived CO2 at the outer surface of the
cardiomyocyte plasma membrane by membrane-anchored, extracellular CA, is
transported into the cell via Na(+)/HCO3 (-) cotransport to counteract
intracellular acidification, while the remaining H(+) stabilizes extracellular pH
at the surface of the plasma membrane during MCT activity to enhance lactate
influx into cardiomyocytes.
PMID- 25118995
TI - Influence of TGFB1 C-509T polymorphism on gastric cancer risk associated with TGF
beta1 expression in the gastric mucosa.
AB - BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) has dual roles
inhibiting and promoting carcinogenesis. Although many researchers have conducted
association studies between TGFB1 C-509T polymorphism and the risk of developing
gastric cancer, the results are not uniform. METHODS: We genotyped 1028 gastric
cancer patients and 958 controls by the polymerase chain reaction-restriction
fragment length polymorphism method. Immunohistochemistry was performed to assess
the expression of TGF-beta1 in the cancer and noncancerous tissues of 120 gastric
cancer patients. mRNA expression was also measured in noncancerous gastric mucosa
by qRT-PCR in the 282 subjects. RESULTS: The CT genotype in the TGFB1 C-509T
polymorphism was associated with an increased risk of gastric cancer development
(adjusted OR 1.35, 95 % CI 1.07-1.71, P = 0.013), especially for intestinal-type
cancer (adjusted OR 1.43, 95 % CI 1.08-1.90, P = 0.014). More frequent TGF-beta1
expression was found in the center of cancer tissue in the TGFB1-509T carrier
group than in the others (90.5 % vs. 72.2 %, P = 0.010). T-carriers also
presented higher expression level of gastric TGF-beta1 mRNA than non T-carriers
(median 1.29 vs. 0.80, P = 0.004) when they were infected by H. pylori. Cancer
patients showed elevated gastric TGFB1gene expression compared to the control
group (median 1.22 vs. 0.89, P = 0.009). CONCLUSIONS: The carcinogenic effect of
TGF-beta1 might be associated with increased gastric TGF-beta1 expression in
subjects with the T allele of TGFB1-509.
PMID- 25118997
TI - Expression of S6K1 in human visceral adipose tissue is upregulated in obesity and
related to insulin resistance and inflammation.
AB - The ribosomal protein S6 kinase 1 (S6K1) is a component of the insulin signalling
pathway that has been proposed as a key molecular factor in insulin resistance
development under conditions of nutrient overload. The aim was to evaluate the
involvement of S6K1 in obesity as well as to explore their association with
visceral adipose tissue (VAT) inflammation. Samples obtained from 40 subjects
were used. Gene expression levels of RPS6KB1 and key inflammatory markers were
analysed in VAT. The effect of insulin on transcript levels of RPS6KB1 in human
differentiated adipocytes was also explored. RPS6KB1 mRNA levels in VAT were
increased (P < 0.05) in obese patients. Insulin treatment significantly enhanced
(P < 0.01) gene expression levels of RPS6KB1 and a positive association (P <
0.05) of RPS6KB1 expression with different markers of insulin resistance was
observed. Moreover, RPS6KB1 gene expression levels were positively correlated
with VAT gene expression levels of the inflammatory markers CCL2, CD68, MMP2,
MMP9, VEGFA and CHI3L1 as well as with mRNA levels of MTOR and MAPK8,
representative players involved in signalling pathways related to S6K1. The
increased levels of S6K1 in obesity and its positive association with insulin
resistance and inflammation suggest a role for this protein in the changes that
take place in VAT in obesity establishing a link between inflammation and a
higher risk for the development of metabolic diseases.
PMID- 25118998
TI - Insulin and GH-IGF-I axis: endocrine pacer or endocrine disruptor?
AB - Growth hormone/insulin-like growth factor (IGF) axis may play a role in
maintaining glucose homeostasis in synergism with insulin. IGF-1 can directly
stimulate glucose transport into the muscle through either IGF-1 or insulin/IGF-1
hybrid receptors. In severely decompensated diabetes including diabetic
ketoacidosis, plasma levels of IGF-1 are low and insulin delivery into the portal
system is required to normalize IGF-1 synthesis and bioavailability.
Normalization of serum IGF-1 correlated with the improvement of glucose
homeostasis during insulin therapy providing evidence for the use of IGF-1 as
biomarker of metabolic control in diabetes. Taking apart the inherent mitogenic
discussion, diabetes treatment using insulins with high affinity for the IGF-1
receptor may act as an endocrine pacer exerting a cardioprotective effect by
restoring the right level of IGF-1 in bloodstream and target tissues, whereas
insulins with low affinity for the IGF-1 receptor may lack this positive effect.
An excessive and indirect stimulation of IGF-1 receptor due to sustained and
chronic hyperinsulinemia over the therapeutic level required to overtake
acute/chronic insulin resistance may act as endocrine disruptor as it may
possibly increase the cardiovascular risk in the short and medium term and
mitogenic/proliferative action in the long term. In conclusion, normal IGF-1 may
be hypothesized to be a good marker of appropriate insulin treatment of the
subject with diabetes and may integrate and make more robust the message coming
from HbA1c in terms of prediction of cardiovascular risk.
PMID- 25118999
TI - Effects of exenatide, insulin, and pioglitazone on liver fat content and body fat
distributions in drug-naive subjects with type 2 diabetes.
AB - Ectopic accumulation of lipids in nonadipose tissues plays a primary role in the
pathogenesis of type 2 diabetes mellitus (T2DM). This study was to examine the
effects of exenatide, insulin, and pioglitazone on liver fat content and body fat
distributions in T2DM. Thirty-three drug-naive T2DM patients (age 52.7 +/- 1.7
years, HbA1c 8.7 +/- 0.2 %, body mass index 24.5 +/- 0.5 kg/m(2)) were randomized
into exenatide, insulin, or pioglitazone for 6 months. Intrahepatic fat (IHF),
visceral fat (VF), and subcutaneous fat (SF) were measured using proton nuclear
magnetic resonance spectroscopy. Plasma tumor necrosis factor alpha (TNFalpha)
and adiponectin were assayed by ELISA. HbA1c declined significantly in all three
groups. Body weight, waist, and serum triglycerides decreased with exenatide.
After interventions, IHF significantly reduced with three treatments (exenatide
Delta = -68 %, insulin Delta = -58 %, pioglitazone Delta = -49 %). Exenatide
reduced VF (Delta = -36 %) and SF (Delta = -13 %), and pioglitazone decreased VF
(Delta = -30 %) with no impact on SF, whereas insulin had no impact on VF or SF.
Levels of TNFalpha (exenatide/insulin/pioglitazone) decreased, and levels of
adiponectin (exenatide/pioglitazone) increased. Analysis showed that DeltaIHF
correlated with DeltaHbA1c and Deltaweight. Besides, DeltaIHF correlated with
Deltatriglycerides and DeltaTNFalpha, but the correlations fell short of
significance after BMI adjustment. By linear regression analysis, DeltaHbA1c
alone explained 41.5 % of the variance of DeltaIHF, and DeltaHbA1c + Deltaweight
explained 57.6 % of the variance. Liver fat content can be significantly reduced
irrespective of using exenatide, insulin, and pioglitazone. Early glycaemic
control plays an important role in slowing progression of fatty liver in T2DM.
PMID- 25119000
TI - Process and formulation variables of pregabalin microspheres prepared by w/o/o
double emulsion solvent diffusion method and their clinical application by animal
modeling studies.
AB - Pregabalin is an anticonvulsant drug used for neuropathic pain and as an adjunct
therapy for partial seizures with or without secondary generalization in adults.
In conventional therapy recommended dose for pregabalin is 75 mg twice daily or
50 mg three times a day, with maximum dosage of 600 mg/d. To achieve maximum
therapeutic effect with a low risk of adverse effects and to reduce often drug
dosing, modified release preparations; such as microspheres might be helpful.
However, most of the microencapsulation techniques have been used for lipophilic
drugs, since hydrophilic drugs like pregabalin, showed low-loading efficiency and
rapid dissolution of compounds into the aqueous continous phase. The purpose of
this study was to improve loading efficiency of a water-soluble drug and modulate
release profiles, and to test the efficiency of the prepared microspheres with
the help of animal modeling studies. Pregabalin is a water soluble drug, and it
was encapsulated within anionic acrylic resin (Eudragit S 100) microspheres by
water in oil in oil (w/o/o) double emulsion solvent diffusion method.
Dichloromethane and corn oil were chosen primary and secondary oil phases,
respectively. The presence of internal water phase was necessary to form stable
emulsion droplets and it accelerated the hardening of microspheres. Tween 80 and
Span 80 were used as surfactants to stabilize the water and corn oil phases,
respectively. The optimum concentration of Tween 80 was 0.25% (v/v) and Span 80
was 0.02% (v/v). The volume of the continous phase was affected the size of the
microspheres. As the volume of the continous phase increased, the size of
microspheres decreased. All microsphere formulations were evaluated with the help
of in vitro characterization parameters. Microsphere formulations (P1-P5)
exhibited entrapment efficiency ranged between 57.00 +/- 0.72 and 69.70 +/-
0.49%; yield ranged between 80.95 +/- 1.21 and 93.05 +/- 1.42%; and mean particle
size were between 136.09 +/- 2.57 and 279.09 +/- 1.97 um. Pregabalin microspheres
having better results among all formulations (Table 3) were chosen for further
studies such as differential scanning calorimetry, Fourier transform infrared
analysis and dissolution studies. In the last step, the best pregabalin
microsphere formulation (P3) was chosen for in vivo animal studies. The
pregabalin-loaded microspheres (P3) and conventional pregabalin capsules were
applied orally in rats for three days, resulted in clinical improvement of cold
allodynia, an indicator of peripheral neuropathy. This result when evaluated
together with the serum pregabalin levels and in vitro release studies suggests
that the pregabalin microspheres prepared with w/o/o double emulsion solvent
diffusion method can be an alternative form for neuropathic pain therapy.
Conclusively, a drug delivery system successfully developed that showed modified
release up to 10 h and could be potentially useful to overcome the frequent
dosing problems associated with pregabalin conventional dosage form.
PMID- 25119003
TI - The role of human papillomavirus infection in the head and neck region and
methods for its detection.
AB - Human papillomaviruses (HPV) are the etiological factors of many benign and
malignant lesions localized in the skin and mucous membranes in the region of the
urogenital organs and head and neck. Currently, most assays for the detection of
HPV are based on detecting the presence of viral nucleic acids, mostly viral DNA.
These molecular techniques can be divided into: 1) methods based on a targeted,
selective amplification of nucleic acids, 2) signal amplification methods, 3)
nucleic acid hybridization assays. This paper presents and explains a number of
different HPV detection methods and provides examples of some commonly available
commercial tests.
PMID- 25119002
TI - Risk factors for intraocular involvement in patients with primary central nervous
system lymphoma.
AB - To determine the risk factors for intraocular involvement in patients with
primary central nervous system lymphoma (PCNSL), a retrospective chart review was
performed on 136 patients who were pathologically diagnosed with PCNSL. The
patients were investigated for demographics, clinical manifestation, and the
profile of immunohistochemical tumor biomarkers, as well as for the presence of
intraocular involvement of lymphoma at diagnosis or during follow-up. The mean
age of the entire cohort was 58.6 +/- 12.4 years, and the mean follow-up period
was 31.1 +/- 30.8 months. Twenty-nine (21 %) patients had an intraocular
involvement, among which 20 (69 %) patients presented with intraocular
involvement at diagnosis of PCNSL and 9 (31 %) patients developed intraocular
involvement after a mean period of 32.4 +/- 33.6 months. Of the patients with
intraocular involvement, 8 (28 %) had no visual symptom at the diagnosis of
ocular invasion. Between those with and without intraocular involvement, no
significant differences were found with respect to the age, sex, and follow-up
period as well as cerebrospinal fluid spread and bone marrow involvement. Among
the immunohistochemical biomarkers, the Ki-67 proliferation index was
significantly higher in patients with intraocular involvement than in patients
without (P = 0.021), but the other investigated biomarkers did not show a
significant difference between the two groups. A Ki-67 level >=80 % was a risk
factor for the intraocular involvement in patients with PCNSL (odds ratio, 2.63).
Median overall survival was 39.0 months in the entire cohort and was not
significantly different between those with and without intraocular involvement (P
= 0.959).
PMID- 25119004
TI - Review of small cell carcinoma of the kidney with focus on clinical and
pathobiological aspects.
AB - Small cell carcinoma (SmCC) of the kidney is extremely rare. In this article, we
present a review of SmCC of the kidney with the focus on clinical and
pathobiological aspects. Macroscopically, this tumor often shows a bulky mass
extensively replacing the renal parenchyma with vascular invasion and metastasis
to lymph nodes. Histologically, the tumor is composed of small cells with scant
cytoplasm, round to oval nuclei, finely granular chromatin and inconspicuous
nucleoli. Rosette or tubular formation may be present. Immunohistochemically,
neoplastic cells show variable positivity for neuron-specific enolase,
chromogranin A, synaptophysin, CD57 (Leu7) and CD56. A dot-like staining pattern
for cytokeratin may also be observed. An electron microscopic examination may
identify electron-dense neurosecretory granules in the cytoplasm. As a
therapeutic option, nephrectomy and systemic chemotherapy should be considered.
However, despite multimodal therapy, most patients have a dismal outcome and die
of widely metastatic disease within one to two years. As there are limited
genetic data on SmCC of the kidney, a large series studying this will be needed
in the future.
PMID- 25119005
TI - Breast pathology after cryotherapy. Histological regression of breast cancer
after cryotherapy.
AB - A breast saving treatment is contemporary the preferred method of treatment with
comparable results in comparing with mastectomy. In this study were evaluated the
effects of cryotherapy by histological verification of changes in post treatment
resection specimens. Fifty-three patients in age of 38-81 year with
histologically confirmed breast cancer in needle biopsies were managed by
cryotherapy between 1999 and 2007. The patients were operated between day 1 and
35 after cryotherapy. The histologic examination of operation materials showed in
all cases at least partial tumor destruction. In general in 54.7% of all handled
cases (29 patient) there was no residual tumor. In 6 cases (22.2%) from group 1
and in 23 cases (88.5%) of group 2 no tumor rest was found. Cryotherapy can lead
to complete destruction of tumoral tissue. In our study all 29 (54.7%) of tumor
free cases after cryotherapy were those with cT1 stage. The experience of
operator and the correct selection of appropriate patients (primarily taking the
tumor size into account) play the most important role for achieving the best
results.
PMID- 25119001
TI - Unyielding progress: recent advances in the treatment of central nervous system
neoplasms with radiosurgery and radiation therapy.
AB - In the past decade, our understanding of the roles of external beam radiotherapy
(EBRT) and stereotactic radiosurgery (SRS) in the management of brain tumors has
dramatically improved. To highlight the changes and contemporary treatment
approaches, we review the indications and outcomes of ionizing radiation for
benign intracranial tumors and brain metastases. For nonfunctioning pituitary
adenomas, SRS is able to achieve radiographic tumor control in at least 90 % of
cases. The rate of SRS-induced endocrine remission for functioning pituitary
adenomas depends on the tumor subtype, but it is generally lower than the rate of
radiographic tumor control. The most common complications from pituitary adenoma
SRS treatment are hypopituitarism and cranial neuropathies. SRS has become the
preferred treatment modality for vestibular schwannomas and skull base
meningiomas less than 3 cm in size. Large vestibular schwannomas and meningiomas
remain best managed with initial surgical resection or EBRT for surgically
ineligible patients. For small to moderately sized brain metastases, there has
been a shift toward treatment of newly diagnosed patients with SRS alone due to
similar local control rates compared with surgical resection. RCTs have shown
combined SRS and whole brain radiation therapy (WBRT) for brain metastases to
decrease rates of local and distant intracranial recurrence compared to SRS
alone. However, the improved intracranial control comes at the expense of poorer
neurocognitive outcomes and without prolonging overall survival. Therefore, WBRT
is generally reserved for salvage therapy. While EBRT has been frequently
supplanted by SRS for the treatment pituitary adenomas and brain metastases, it
still proves useful in selected cases of large lesions which are not amenable to
surgical debulking or for those with widespread disease, poor performance status,
and short life expectancy. In recent years, the scope of SRS has extended beyond
the intracranial space to include extradural and intradural spinal tumors.
PMID- 25119006
TI - Selected morphologic features influencing the prognosis of conventional renal
cell carcinomas co-expressing P53 and MDM2.
AB - Renal cell carcinoma is the most deadly of common urologic malignancies. The
classical prognostic factors, including tumor type, grade and stage, as well as
performance status of the patient, offer important information, but there is a
need for new biomarkers which could improve the quality of prognostication. It
has been proposed that tumors co-expressing P53 and MDM2 could represent a
specific, more aggressive subgroup. The aim of the study was to explore this
hypothesis using tissue microarrays, using two different anti-P53 antibodies. The
material analyzed consisted of 470 cases of renal clear cell carcinoma. Reaction
for P53 was positive in 15.1 or 13.2% of cases, depending on the antibody used.
Reaction for MDM2 was positive in 37.9% of cases; 6.5 or 5.3% of cases
coexpressed P53 and MDM2. Both P53-positive and double P53/MDM2-positive cases
were higher grade and more likely to contain a sarcomatoid component, but their
stage was similar to negative cases. PAb1081 P53-positive MDM2-positive cases
were larger than the rest of the tumors (7.6 cm vs. 6.1 cm, p < 0.001). Our data
support the hypothesis of prognostic significance of P53, and double P53/MDM2
positivity, yet further studies are needed to clarify the issue.
PMID- 25119007
TI - Evaluation of calretinin immunohistochemistry as an additional tool in confirming
the diagnosis of Hirschsprung disease.
AB - Hirschsprung disease (HD) is a congenital malformation defined as the absence of
myenteric and submucosal ganglion cells (GCs) in the distal rectum and variable
length of the contiguous bowel. The aim of this study was to assess the utility
of calretinin immunochemistry in comparison with that of standard histology
complemented with acetylcholinesterase (AChE) histochemistry routinely employed
at our institution to evaluate rectal biopsies carried out for suspicion of HD.
Twenty-one rectal biopsies were reviewed, including 14 from patients with
suspected HD, 6 from infants with necrotizing enterocolitis (NEC), and 1 from a
patient diagnosed with spontaneous intestinal perforation (SIP). Sections stained
with hematoxylin-eosin (HE) revealed absence of ganglion cells in 13 cases which
included 11 patients with HD and 2 patients with NEC. Among 13 cases of
aganglionosis the AChE reaction pattern was consistent with HD in 2 patients.
Calretinin positivity was observed in all rectal biopsies showing the presence of
GC, and the staining was consistently absent in all cases of aganglionosis. In 6
rectal biopsies in which abnormal acetylcholinesterase (AChE) staining was not
seen, loss of calretinin immunoreactivity helped establish the diagnosis of HD.
PMID- 25119008
TI - Study of nano-hydroxyapatite/zirconia stabilized with yttria in bone healing:
histopathological study in rabbit model.
AB - Acceleration of bone healing has always been a major challenge in orthopedic
surgery, the aim of this study was an evaluation of the biological effects of
zirconia-stabilized yttria on bone healing, using an in vivo model. Nano
hydroxyapatite powder with zirconia-stabilized yttria were inserted in rabbit
tibia and then histologically analyzed and compared with non-treated controls so
thirty six. New Zealand white male rabbits randomly divided into two groups of 18
rabbits each. A cortical hole of 4 mm diameter and 8 mm depth in each tibia was
drilled. In group I, the defect was left empty, whereas in group II, the bone
defect was packed with nano-hydroxyapatite/5% zirconia stabilized with yttria.
Histological evaluations were performed at two, four and six weeks after the
implantation. Microscopic changes on two groups along with the time course were
scored and statistical analysis showed that the average scores in group II were
significantly higher than the other groups (p < 0.05). Histological analysis was
shown to be significantly improved by the nano-hydroxyapatite/5% zirconia
stabilized with yttria compared with the control group, suggesting that this
biomaterial promote the healing of cortical bone, presumably by acting as an
osteoconductive.
PMID- 25119009
TI - The comparison of nuclear ubiquitous casein and cyclin-dependent kinases
substrate (NUCKS) with Ki67 proliferation marker expression in common skin
tumors.
AB - Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) is a
chromosomal protein of unknown function. Its amino acid composition and structure
of its DNA binding domain resemble those of high mobility group A (HMGA) proteins
which are associated with various malignancies. Since changes in expression of
HMGA are considered as a marker of tumor progression, it is possible that similar
changes in expression of NUCKS could be a useful tool in diagnosis of malignant
skin tumors. To investigate this assumption we used specific antibodies against
NUCKS for immunohistochemistry of squamous (SCC) and basal cell carcinoma (BCC)
as well as keratoacanthoma (KA). We found high expression of NUCKS in nuclei of
SCC and BCC cells which exceeded expression of the well-known proliferation
marker Ki67. Expression of NUCKS in benign KA was much below that of malignant
tumors. With the present study and based on our previous experience we would like
to suggest the NUCKS protein as a novel proliferation marker for
immunohistochemical evaluation of formalin-fixed and paraffin-embedded skin tumor
specimens. We would like to emphasize that NUCKS abundance in malignant skin
tumors is higher than that of the well-known proliferation marker Ki67, thus
allowing more precise assessment of tumor proliferation potential.
PMID- 25119010
TI - Cadmium in urothelial carcinoma of the bladder.
AB - The aim of this study was to examine the relationship between cadmium (Cd) and
bladder cancer (urothelial carcinoma of the bladder). Cadmium concentrations in
two 36-sample series of bladder cancer tissue and blood, from patients with the
neoplasm, were matched with those of the control group. The amount of heavy metal
in every tissue sample was determined using atomic absorption spectrometry. This
was correlated with tumour stage. While the median cadmium concentration levels
reached statistically lower values in the bladder cancer tissue, as compared with
the non-cancer one (11.695 ng/g and 56.32 ng/g respectively, p < 0.001), the
median Cd levels in the blood of the patients with this carcinoma showed no
statistical difference when compared to those of the control group (8.237 MUg/l
and 7.556 MUg/l respectively, p = 0.121). The median levels of cadmium in the
bladder tissue, depending on the stage of the tumour, compared with the tissue
without the neoplasm, observed the same relationship for both non-muscle invasive
and muscle-invasive tumours (p < 0.002 and p < 0.02 respectively). This study has
shown that patients with urothelial carcinoma of the bladder had lower tissue
cadmium levels than people without tumour while no difference in the Cd blood
levels between the two groups of patients under investigation was found.
PMID- 25119011
TI - Phosphate nephropathy after administration of bowel purgative containing sodium
phosphate - a case report.
AB - A 65-year-old woman was admitted to the hospital with an elevated serum
creatinine concentration associated with leukocyturia and erythrocyturia. Past
medical history analysis revealed that four months before current hospitalization
she had been subjected to colonoscopy preceded by the administration of oral
sodium phosphate solution (OSP) as preparation for this procedure. Kidney biopsy
revealed mild chronic tubulo-interstitial inflammation and scarring with
prominent cortical tubular calcium phosphate deposits. The diagnosis of phosphate
nephropathy, most probably secondary to OSP ingestion was made. During follow-up
the renal function remained impaired but stable with eGFR of 25 ml/min/1.73 m2.
The patient is currently under the care of the nephrology clinic.
PMID- 25119012
TI - Appearance of estrogen positive bilateral breast carcinoma with HER2 gene
amplification in a patient with aplastic anemia.
AB - Immunosuppressive therapy is one of the standard therapy protocols for aplastic
anemia (AA). However, immunosuppressive therapy and androgenic steroids can
promote development of solid tumors such as squamous carcinoma, head and neck
tumors, adenocarcinoma of the stomach, hepatocarcinoma and breast carcinoma in
long surviving patients with aplastic anemia. We present here a rare case of a 56
year-old woman in whom bilateral adenocarcinoma of the breast developed 11 years
after the start of immunosuppressive and androgenic steroid therapy for aplastic
anemia. Histological examination showed invasive ductal carcinoma with intense
nuclear staining for estrogen receptors. Her2 immunohistochemistry was positive
for 80% of stained cells, and chromogenic in situ hybridization showed a high
level of HER2 gene amplification. This case indicated that a new therapy option
is needed for estimation and evaluation to avoid the consequence of cancer
occurrence.
PMID- 25119013
TI - Primary mucinous cystadenocarcinoma of the breast with amplification of the HER2
gene confirmed by FISH - case report and review of the literature.
AB - Fifty five-years-old woman was presented to the general surgery upon the
palpation of a mass in her left breast. In the excisional biopsy performed,
partially cystic tumor of 2 * 1 cm with solid areas was macroscopically observed.
After through microscopic examination, the patient was diagnosed as invasive
mucinous cystadenocarcinoma and the tumor was found to be ER- and PR-negative and
C-erbB2 (2+). In the fluorescent in situ hybridization, HER2/neu gene
amplification was observed. Here, we present the clinical, cytological,
morphological and immunohistochemical features of a very rare type of breast
carcinoma, mucinous cystadenocarcinoma of the breast, with the review of the
relevant literature.
PMID- 25119014
TI - Nested variant of urothelial carcinoma of renal pelvis - a case report.
AB - We report a case of an 80-year-old woman with a very rare subtype of urothelial
carcinoma - nested variant of urothelial carcinoma mimicking physiological von
Brunn's nests. Optimal treatment of NVUC has not been determined due to the small
number of cases, as well as the lack of randomized and follow-up studies. In our
case the right retroperitoneal nephroureterectomy was chosen.
PMID- 25119015
TI - Bilateral pheochromocytoma/intra-adrenal paraganglioma in von Hippel-Lindau
patient causing acute myocardial infarction.
AB - A 26-year-old male presented to the emergency department complaining of
obstipation, severe headache and abdominal pain. An autopsy revealed bilateral
pheochromocytoma and acute myocardial infarction. The tumor cells showed positive
immunoreactivity of both chromogranin A and synaptophysin and were negative for
adrenocortical markers such as SF-1, c17, scc, 3?-HSD as well as SDHB, suggesting
a germline mutation of the gene SDHB or SDHD. Molecular genetic analyses did not
show a mutation in these two genes, but a mutation in the VHL gene, in exon 3:
VHL c.499C>T. This is a missense mutation and causes an amino acid change
(Arg167Trp).
PMID- 25119016
TI - Hodgkin's lymphoma mimicking tuberculosis in cervical lymph nodes.
AB - The authors present a case description of an 81-year-old male with general
symptoms (fever, night sweats, weight loss) and cervical/supraclavicular
lymphadenopathy. The revised lymph node histopathological examination revealed
nodular sclerosis classical Hodgkin's lymphoma associated with abundant
tuberculosis-mimicking granulomatous reaction. The diagnosis may be difficult due
to similarities in clinical course, laboratory tests and imaging. The morphology
of Hodgkin-Reed-Sternberg cells and the immunohistochemical profile are the most
helpful in differential diagnosis. In cases where granulomas coexist with
negative acid-fast staining, pathologists should always recommend evaluation of
further and broader diagnostic procedures to exclude Mycobacterium tuberculosis
infection.
PMID- 25119017
TI - Breast mass detection using slice conspicuity in 3D reconstructed digital breast
volumes.
AB - In digital breast tomosynthesis, the three dimensional (3D) reconstructed volumes
only provide quasi-3D structure information with limited resolution along the
depth direction due to insufficient sampling in depth direction and the limited
angular range. The limitation could seriously hamper the conventional 3D image
analysis techniques for detecting masses because the limited number of projection
views causes blurring in the out-of-focus planes. In this paper, we propose a
novel mass detection approach using slice conspicuity in the 3D reconstructed
digital breast volumes to overcome the above limitation. First, to overcome the
limited resolution along the depth direction, we detect regions of interest
(ROIs) on each reconstructed slice and separately utilize the depth directional
information to combine the ROIs effectively. Furthermore, we measure the
blurriness of each slice for resolving the degradation of performance caused by
the blur in the out-of-focus plane. Finally, mass features are extracted from the
selected in focus slices and analyzed by a support vector machine classifier to
reduce the false positives. Comparative experiments have been conducted on a
clinical data set. Experimental results demonstrate that the proposed approach
outperforms the conventional 3D approach by achieving a high sensitivity with a
small number of false positives.
PMID- 25119019
TI - Digital divide 2.0: the role of social networking sites in seeking health
information online from a longitudinal perspective.
AB - Adopting a longitudinal angle, this study analyzed data from the Pew Internet's
Health Tracking Survey in 2006, 2008, and 2010 to identify potential
communication inequalities in social networking site use. Results showed that
with the growing role of social networking site use in predicting people's
likelihood of seeking health information online, the socioeconomic and
demographic factors that contributed to the disparities in social networking site
use could also lead to disparities in seeking health information online. Also,
results indicated that people are more likely to seek heath-related information
online if they or their close family or friends have a chronic disease situation.
PMID- 25119021
TI - Calcification of arteries supplying the gastric tube: a new risk factor for
anastomotic leakage after esophageal surgery.
AB - PURPOSE: To evaluate the association between the amount and location of
calcifications of the supplying arteries of the gastric tube, as determined with
a vascular calcification scoring system, and the occurrence of anastomotic
leakage after esophagectomy with gastric tube reconstruction in patients with
esophageal cancer. MATERIALS AND METHODS: Institutional review board approval was
obtained, and the informed consent requirement was waived for this retrospective
study. Consecutive patients who underwent elective esophagectomy for cancer with
gastric tube reconstruction and cervical anastomosis between 2003 and 2012 were
identified from a prospective database. Vascular calcification scores were
retrospectively assigned by reviewing the routine preoperative computed
tomographic (CT) images. In patients with anastomotic leakage, presence and
severity of calcifications of the aorta (score of 0-2), celiac axis (score of 0
2), right postceliac arteries (common hepatic, gastroduodenal, and right
gastroepiploic arteries; score of 0-1), and left postceliac arteries (splenic and
left gastroepiploic arteries, score of 0-1) along with patient- and procedure
related characteristics were compared with those of patients without leakage by
using multivariate logistic regression analysis. RESULTS: Of 246 patients, 58
(24%) experienced anastomotic leakage. No significant differences in patient
related factors were found between patients with leakage and those without
leakage, with the exception of more chronic use of steroids in the leakage group
(7% [four of 58] vs 0% [0 of 188], P = .003). At univariate analysis, leakage was
more common in patients with calcification of the aorta (27% [28 of 102] and 35%
[13 of 37] vs 16% [17 of 107], P = .029) and the right postceliac arteries (55%
[six of 11] vs 22% [52 of 235], P = .013). At multivariate analysis, both minor
(odds ratio, 2.00; 95% confidence interval: 1.02, 3.94) and major (odds ratio,
2.87; 95% confidence interval: 1.22, 6.72) aortic calcifications were associated
with leakage. Also, an independent association with leakage was found for
calcifications of the right postceliac arteries (odds ratio, 4.22; 95% confidence
interval: 1.24, 14.4). CONCLUSION: Atherosclerotic calcification of the aorta and
right postceliac arteries that supply the gastric tube is an independent risk
factor for anastomotic leakage after esophagectomy.
PMID- 25119022
TI - Diagnostic utility of second-look US for breast lesions identified at MR imaging:
systematic review and meta-analysis.
AB - PURPOSE: To evaluate the diagnostic utility of second-look ultrasonography (US)
in the assessment of lesions identified at breast magnetic resonance (MR)
imaging. MATERIALS AND METHODS: A systematic review of the PubMed database for
articles published up to January 6, 2013, was performed by using predefined
search terms applied in a standardized manner. Second-look US studies for the
assessment of breast lesions identified at MR imaging were eligible for this meta
analysis. Two independent reviewers performed the literature review and data
extraction. Eligible studies presented data on the number of lesions examined and
the number of lesions detected at second-look US. The reference standard for
lesion diagnosis was either histopathologic or follow-up examination. Sources of
bias were assessed by using the Quality Assessment of Diagnostic Accuracy Studies
2, or QUADAS-2 Quality Assessment of Diagnostic Accuracy Studies 2 , tool.
Statistical analysis included data pooling, heterogeneity testing, and meta
regression. RESULTS: Seventeen studies that included benign and malignant lesions
met the inclusion criteria. The general lesion detection rate at second-look US
was very heterogeneous and ranged between 22.6% and 82.1% (pooled rate, 57.5%
[1266 of 2201]; 95% confidence interval [ CI confidence interval ]: 50.0%, 64.1%
[random-effects model]; I(2) = 90.9%; P < .0001). The highest second-look US
detection rates were observed for mass lesions (as opposed to nonmass lesions)
and malignant (vs benign) lesions (P < .001 for both). Pooled positive and
negative predictive values (positive or negative second-look US correlates of MR
imaging-detected malignant or benign lesions) were calculated as 30.7% (95% CI
confidence interval : 25.3%, 36.4%; I(2) = 75.4%; P < .0001) and 87.8% (95% CI
confidence interval : 82.0%, 92.7%; I(2) = 82.1%; P < .0001), respectively, by
using random-effects models. CONCLUSION: The results of this study demonstrated
variable utility of second-look US in MR imaging-detected lesions, as lesion
detection rates were very heterogeneous. Subgroup analysis showed that malignant
and mass lesions were more likely to be detected at second-look US. Furthermore,
malignancy was not excluded if a lesion was not detected at second-look US.
PMID- 25119020
TI - Biallelic alterations of the large tumor suppressor 1 (LATS1) gene in
infiltrative, but not superficial, basal cell carcinomas in a Japanese patient
with nevoid basal cell carcinoma syndrome.
AB - The present study was conducted to address the molecular pathogenesis underlying
the progression of basal cell carcinoma (BCC) in a nevoid basal cell carcinoma
syndrome (NBCCS) patient. We analyzed infiltrative BCCs that invaded the
subcutaneous tissue of the scalp and penetrated the skull in a 61-year-old
Japanese female. Whole-exome sequencing validated by Sanger sequencing was
applied to assess the subcutaneously infiltrative BCCs. Differences in genetic
alterations between the superficial and infiltrative BCCs were also examined. Of
particular note, the infiltrative BCCs showed a nonsense mutation, c.943C>T,
resulting in p.Q315X in the large tumor suppressor 1 (LATS1) gene, as well as the
loss of the wild-type allele of LATS1 (6q25.1), thus indicating that the LATS1
gene was biallelically disrupted. In contrast, no alterations in the LATS1 gene
were observed in the superficial BCCs. Additionally, a loss of heterozygosity
analysis revealed that the distal region of chromosome 6q where LATS1 locates was
deleted in a heterozygous manner. The present results imply that the biallelic
disruption of LATS1 is a progressive factor of the infiltrative BCCs observed in
this NBCCS patient and suggest that the Hippo pathway is a potential therapeutic
target in cases of infiltrative BCC.
PMID- 25119018
TI - Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin
lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B
cell lymphoma.
AB - The cancer microenvironment plays a pivotal role in oncogenesis, containing a
number of regulatory cells that attenuate the anti-neoplastic immune response.
While the negative prognostic impact of regulatory T cells (Tregs) in the context
of most solid tissue tumors is well established, their role in lymphoid
malignancies remains unclear. T cells expressing FOXP3 and Helios were documented
in the fine needle aspirates of affected lymph nodes of dogs with spontaneous
multicentric B cell lymphoma (BCL), proposed to be a model for human non-Hodgkin
lymphoma. Multivariable analysis revealed that the frequency of lymph node
FOXP3(+) T cells was an independent negative prognostic factor, impacting both
progression-free survival (hazard ratio 1.10; p = 0.01) and overall survival
(hazard ratio 1.61; p = 0.01) when comparing dogs showing higher than the median
FOXP3 expression with those showing the median value of FOXP3 expression or less.
Taken together, these data suggest the existence of a population of Tregs
operational in canine multicentric BCL that resembles thymic Tregs, which we
speculate are co-opted by the tumor from the periphery. We suggest that canine
multicentric BCL represents a robust large animal model of human diffuse large
BCL, showing clinical, cytological and immunophenotypic similarities with the
disease in man, allowing comparative studies of immunoregulatory mechanisms.
PMID- 25119023
TI - Crossed cerebellar diaschisis due to cerebral diffuse large B cell lymphoma on
18F-FDG PET/CT.
PMID- 25119024
TI - Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial
function.
AB - Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in
western countries, with a median survival of 6 months and an extremely low
percentage of long-term surviving patients. KRAS mutations are known to be a
driver event of PDAC, but targeting mutant KRAS has proved challenging. Targeting
oncogene-driven signalling pathways is a clinically validated approach for
several devastating diseases. Still, despite marked tumour shrinkage, the
frequency of relapse indicates that a fraction of tumour cells survives shut down
of oncogenic signalling. Here we explore the role of mutant KRAS in PDAC
maintenance using a recently developed inducible mouse model of mutated Kras
(Kras(G12D), herein KRas) in a p53(LoxP/WT) background. We demonstrate that a
subpopulation of dormant tumour cells surviving oncogene ablation (surviving
cells) and responsible for tumour relapse has features of cancer stem cells and
relies on oxidative phosphorylation for survival. Transcriptomic and metabolic
analyses of surviving cells reveal prominent expression of genes governing
mitochondrial function, autophagy and lysosome activity, as well as a strong
reliance on mitochondrial respiration and a decreased dependence on glycolysis
for cellular energetics. Accordingly, surviving cells show high sensitivity to
oxidative phosphorylation inhibitors, which can inhibit tumour recurrence. Our
integrated analyses illuminate a therapeutic strategy of combined targeting of
the KRAS pathway and mitochondrial respiration to manage pancreatic cancer.
PMID- 25119025
TI - Mechanism of Dis3l2 substrate recognition in the Lin28-let-7 pathway.
AB - The pluripotency factor Lin28 inhibits the biogenesis of the let-7 family of
mammalian microRNAs. Lin28 is highly expressed in embryonic stem cells and has a
fundamental role in regulation of development, glucose metabolism and tissue
regeneration. Overexpression of Lin28 is correlated with the onset of numerous
cancers, whereas let-7, a tumour suppressor, silences several human oncogenes.
Lin28 binds to precursor let-7 (pre-let-7) hairpins, triggering the 3' oligo
uridylation activity of TUT4 and TUT7 (refs 10-12). The oligoU tail added to pre
let-7 serves as a decay signal, as it is rapidly degraded by Dis3l2 (refs 13,
14), a homologue of the catalytic subunit of the RNA exosome. The molecular basis
of Lin28-mediated recruitment of TUT4 and TUT7 to pre-let-7 and its subsequent
degradation by Dis3l2 is largely unknown. To examine the mechanism of Dis3l2
substrate recognition we determined the structure of mouse Dis3l2 in complex with
an oligoU RNA to mimic the uridylated tail of pre-let-7. Three RNA-binding
domains form an open funnel on one face of the catalytic domain that allows RNA
to navigate a path to the active site different from that of its exosome
counterpart. The resulting path reveals an extensive network of uracil-specific
interactions spanning the first 12 nucleotides of an oligoU-tailed RNA. We
identify three U-specificity zones that explain how Dis3l2 recognizes, binds and
processes uridylated pre-let-7 in the final step of the Lin28-let-7 pathway.
PMID- 25119029
TI - Earth science: Warning signs of the Iquique earthquake.
PMID- 25119027
TI - Abrupt glacial climate shifts controlled by ice sheet changes.
AB - During glacial periods of the Late Pleistocene, an abundance of proxy data
demonstrates the existence of large and repeated millennial-scale warming
episodes, known as Dansgaard-Oeschger (DO) events. This ubiquitous feature of
rapid glacial climate change can be extended back as far as 800,000 years before
present (BP) in the ice core record, and has drawn broad attention within the
science and policy-making communities alike. Many studies have been dedicated to
investigating the underlying causes of these changes, but no coherent mechanism
has yet been identified. Here we show, by using a comprehensive fully coupled
model, that gradual changes in the height of the Northern Hemisphere ice sheets
(NHISs) can alter the coupled atmosphere-ocean system and cause rapid glacial
climate shifts closely resembling DO events. The simulated global climate
responses--including abrupt warming in the North Atlantic, a northward shift of
the tropical rainbelts, and Southern Hemisphere cooling related to the bipolar
seesaw--are generally consistent with empirical evidence. As a result of the
coexistence of two glacial ocean circulation states at intermediate heights of
the ice sheets, minor changes in the height of the NHISs and the amount of
atmospheric CO2 can trigger the rapid climate transitions via a local positive
atmosphere-ocean-sea-ice feedback in the North Atlantic. Our results, although
based on a single model, thus provide a coherent concept for understanding the
recorded millennial-scale variability and abrupt climate changes in the coupled
atmosphere-ocean system, as well as their linkages to the volume of the
intermediate ice sheets during glacials.
PMID- 25119028
TI - Continuing megathrust earthquake potential in Chile after the 2014 Iquique
earthquake.
AB - The seismic gap theory identifies regions of elevated hazard based on a lack of
recent seismicity in comparison with other portions of a fault. It has
successfully explained past earthquakes (see, for example, ref. 2) and is useful
for qualitatively describing where large earthquakes might occur. A large
earthquake had been expected in the subduction zone adjacent to northern Chile,
which had not ruptured in a megathrust earthquake since a M ~8.8 event in 1877.
On 1 April 2014 a M 8.2 earthquake occurred within this seismic gap. Here we
present an assessment of the seismotectonics of the March-April 2014 Iquique
sequence, including analyses of earthquake relocations, moment tensors, finite
fault models, moment deficit calculations and cumulative Coulomb stress transfer.
This ensemble of information allows us to place the sequence within the context
of regional seismicity and to identify areas of remaining and/or elevated hazard.
Our results constrain the size and spatial extent of rupture, and indicate that
this was not the earthquake that had been anticipated. Significant sections of
the northern Chile subduction zone have not ruptured in almost 150 years, so it
is likely that future megathrust earthquakes will occur to the south and
potentially to the north of the 2014 Iquique sequence.
PMID- 25119026
TI - Noncoding RNA transcription targets AID to divergently transcribed loci in B
cells.
AB - The vast majority of the mammalian genome has the potential to express noncoding
RNA (ncRNA). The 11-subunit RNA exosome complex is the main source of cellular 3'
5' exoribonucleolytic activity and potentially regulates the mammalian noncoding
transcriptome. Here we generated a mouse model in which the essential subunit
Exosc3 of the RNA exosome complex can be conditionally deleted. Exosc3-deficient
B cells lack the ability to undergo normal levels of class switch recombination
and somatic hypermutation, two mutagenic DNA processes used to generate antibody
diversity via the B-cell mutator protein activation-induced cytidine deaminase
(AID). The transcriptome of Exosc3-deficient B cells has revealed the presence of
many novel RNA exosome substrate ncRNAs. RNA exosome substrate RNAs include xTSS
RNAs, transcription start site (TSS)-associated antisense transcripts that can
exceed 500 base pairs in length and are transcribed divergently from cognate
coding gene transcripts. xTSS-RNAs are most strongly expressed at genes that
accumulate AID-mediated somatic mutations and/or are frequent translocation
partners of DNA double-strand breaks generated at Igh in B cells. Strikingly,
translocations near TSSs or within gene bodies occur over regions of RNA exosome
substrate ncRNA expression. These RNA exosome-regulated, antisense-transcribed
regions of the B-cell genome recruit AID and accumulate single-strand DNA
structures containing RNA-DNA hybrids. We propose that RNA exosome regulation of
ncRNA recruits AID to single-strand DNA-forming sites of antisense and divergent
transcription in the B-cell genome, thereby creating a link between ncRNA
transcription and overall maintenance of B-cell genomic integrity.
PMID- 25119030
TI - Developmental biology: It takes muscle to make blood cells.
PMID- 25119031
TI - Immunology: Mammalian watchdog targets bacteria.
PMID- 25119032
TI - Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5'-diphosphates.
AB - Mammalian cells possess mechanisms to detect and defend themselves from invading
viruses. In the cytosol, the RIG-I-like receptors (RLRs), RIG-I (retinoic acid
inducible gene I; encoded by DDX58) and MDA5 (melanoma differentiation-associated
gene 5; encoded by IFIH1) sense atypical RNAs associated with virus infection.
Detection triggers a signalling cascade via the adaptor MAVS that culminates in
the production of type I interferons (IFN-alpha and beta; hereafter IFN), which
are key antiviral cytokines. RIG-I and MDA5 are activated by distinct viral RNA
structures and much evidence indicates that RIG-I responds to RNAs bearing a
triphosphate (ppp) moiety in conjunction with a blunt-ended, base-paired region
at the 5'-end (reviewed in refs 1, 2, 3). Here we show that RIG-I also mediates
antiviral responses to RNAs bearing 5'-diphosphates (5'pp). Genomes from
mammalian reoviruses with 5'pp termini, 5'pp-RNA isolated from yeast L-A virus,
and base-paired 5'pp-RNAs made by in vitro transcription or chemical synthesis,
all bind to RIG-I and serve as RIG-I agonists. Furthermore, a RIG-I-dependent
response to 5'pp-RNA is essential for controlling reovirus infection in cultured
cells and in mice. Thus, the minimal determinant for RIG-I recognition is a base
paired RNA with 5'pp. Such RNAs are found in some viruses but not in uninfected
cells, indicating that recognition of 5'pp-RNA, like that of 5'ppp-RNA, acts as a
powerful means of self/non-self discrimination by the innate immune system.
PMID- 25119033
TI - Enhanced neonatal Fc receptor function improves protection against primate SHIV
infection.
AB - To protect against human immunodeficiency virus (HIV-1) infection, broadly
neutralizing antibodies (bnAbs) must be active at the portals of viral entry in
the gastrointestinal or cervicovaginal tracts. The localization and persistence
of antibodies at these sites is influenced by the neonatal Fc receptor (FcRn),
whose role in protecting against infection in vivo has not been defined. Here, we
show that a bnAb with enhanced FcRn binding has increased gut mucosal tissue
localization, which improves protection against lentiviral infection in non-human
primates. A bnAb directed to the CD4-binding site of the HIV-1 envelope (Env)
protein (denoted VRC01) was modified by site-directed mutagenesis to increase its
binding affinity for FcRn. This enhanced FcRn-binding mutant bnAb, denoted VRC01
LS, displayed increased transcytosis across human FcRn-expressing cellular
monolayers in vitro while retaining FcgammaRIIIa binding and function, including
antibody-dependent cell-mediated cytotoxicity (ADCC) activity, at levels similar
to VRC01 (the wild type). VRC01-LS had a threefold longer serum half-life than
VRC01 in non-human primates and persisted in the rectal mucosa even when it was
no longer detectable in the serum. Notably, VRC01-LS mediated protection superior
to that afforded by VRC01 against intrarectal infection with simian-human
immunodeficiency virus (SHIV). These findings suggest that modification of FcRn
binding provides a mechanism not only to increase serum half-life but also to
enhance mucosal localization that confers immune protection. Mutations that
enhance FcRn function could therefore increase the potency and durability of
passive immunization strategies to prevent HIV-1 infection.
PMID- 25119034
TI - Inflammatory caspases are innate immune receptors for intracellular LPS.
AB - The murine caspase-11 non-canonical inflammasome responds to various bacterial
infections. Caspase-11 activation-induced pyroptosis, in response to cytoplasmic
lipopolysaccharide (LPS), is critical for endotoxic shock in mice. The mechanism
underlying cytosolic LPS sensing and the responsible pattern recognition receptor
are unknown. Here we show that human monocytes, epithelial cells and
keratinocytes undergo necrosis upon cytoplasmic delivery of LPS. LPS-induced
cytotoxicity was mediated by human caspase-4 that could functionally complement
murine caspase-11. Human caspase-4 and the mouse homologue caspase-11 (hereafter
referred to as caspase-4/11) and also human caspase-5, directly bound to LPS and
lipid A with high specificity and affinity. LPS associated with endogenous
caspase-11 in pyroptotic cells. Insect-cell purified caspase-4/11 underwent
oligomerization upon LPS binding, resulting in activation of the caspases.
Underacylated lipid IVa and lipopolysaccharide from Rhodobacter sphaeroides (LPS
RS) could bind to caspase-4/11 but failed to induce their oligomerization and
activation. LPS binding was mediated by the CARD domain of the caspase. Binding
deficient CARD-domain point mutants did not respond to LPS with oligomerization
or activation and failed to induce pyroptosis upon LPS electroporation or
bacterial infections. The function of caspase-4/5/11 represents a new mode of
pattern recognition in immunity and also an unprecedented means of caspase
activation.
PMID- 25119035
TI - Piezo1 integration of vascular architecture with physiological force.
AB - The mechanisms by which physical forces regulate endothelial cells to determine
the complexities of vascular structure and function are enigmatic. Studies of
sensory neurons have suggested Piezo proteins as subunits of Ca(2+)-permeable non
selective cationic channels for detection of noxious mechanical impact. Here we
show Piezo1 (Fam38a) channels as sensors of frictional force (shear stress) and
determinants of vascular structure in both development and adult physiology.
Global or endothelial-specific disruption of mouse Piezo1 profoundly disturbed
the developing vasculature and was embryonic lethal within days of the heart
beating. Haploinsufficiency was not lethal but endothelial abnormality was
detected in mature vessels. The importance of Piezo1 channels as sensors of blood
flow was shown by Piezo1 dependence of shear-stress-evoked ionic current and
calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer
sensitivity to shear stress on otherwise resistant cells. Downstream of this
calcium influx there was protease activation and spatial reorganization of
endothelial cells to the polarity of the applied force. The data suggest that
Piezo1 channels function as pivotal integrators in vascular biology.
PMID- 25119036
TI - Required enhancer-matrin-3 network interactions for a homeodomain transcription
program.
AB - Homeodomain proteins, described 30 years ago, exert essential roles in
development as regulators of target gene expression; however, the molecular
mechanisms underlying transcriptional activity of homeodomain factors remain
poorly understood. Here investigation of a developmentally required POU
homeodomain transcription factor, Pit1 (also known as Pou1f1), has revealed that,
unexpectedly, binding of Pit1-occupied enhancers to a nuclear matrin-3-rich
network/architecture is a key event in effective activation of the Pit1-regulated
enhancer/coding gene transcriptional program. Pit1 association with Satb1 (ref.
8) and beta-catenin is required for this tethering event. A naturally occurring,
dominant negative, point mutation in human PIT1(R271W), causing combined
pituitary hormone deficiency, results in loss of Pit1 association with beta
catenin and Satb1 and therefore the matrin-3-rich network, blocking Pit1
dependent enhancer/coding target gene activation. This defective activation can
be rescued by artificial tethering of the mutant R271W Pit1 protein to the matrin
3 network, bypassing the pre-requisite association with beta-catenin and Satb1
otherwise required. The matrin-3 network-tethered R271W Pit1 mutant, but not the
untethered protein, restores Pit1-dependent activation of the enhancers and
recruitment of co-activators, exemplified by p300, causing both enhancer RNA
transcription and target gene activation. These studies have thus revealed an
unanticipated homeodomain factor/beta-catenin/Satb1-dependent localization of
target gene regulatory enhancer regions to a subnuclear architectural structure
that serves as an underlying mechanism by which an enhancer-bound homeodomain
factor effectively activates developmental gene transcriptional programs.
PMID- 25119037
TI - Inappropriate p53 activation during development induces features of CHARGE
syndrome.
AB - CHARGE syndrome is a multiple anomaly disorder in which patients present with a
variety of phenotypes, including ocular coloboma, heart defects, choanal atresia,
retarded growth and development, genitourinary hypoplasia and ear abnormalities.
Despite 70-90% of CHARGE syndrome cases resulting from mutations in the gene
CHD7, which encodes an ATP-dependent chromatin remodeller, the pathways
underlying the diverse phenotypes remain poorly understood. Surprisingly, our
studies of a knock-in mutant mouse strain that expresses a stabilized and
transcriptionally dead variant of the tumour-suppressor protein p53
(p53(25,26,53,54)), along with a wild-type allele of p53 (also known as Trp53),
revealed late-gestational embryonic lethality associated with a host of
phenotypes that are characteristic of CHARGE syndrome, including coloboma, inner
and outer ear malformations, heart outflow tract defects and craniofacial
defects. We found that the p53(25,26,53,54) mutant protein stabilized and
hyperactivated wild-type p53, which then inappropriately induced its target genes
and triggered cell-cycle arrest or apoptosis during development. Importantly,
these phenotypes were only observed with a wild-type p53 allele, as
p53(25,26,53,54)(/-) embryos were fully viable. Furthermore, we found that CHD7
can bind to the p53 promoter, thereby negatively regulating p53 expression, and
that CHD7 loss in mouse neural crest cells or samples from patients with CHARGE
syndrome results in p53 activation. Strikingly, we found that p53 heterozygosity
partially rescued the phenotypes in Chd7-null mouse embryos, demonstrating that
p53 contributes to the phenotypes that result from CHD7 loss. Thus, inappropriate
p53 activation during development can promote CHARGE phenotypes, supporting the
idea that p53 has a critical role in developmental syndromes and providing
important insight into the mechanisms underlying CHARGE syndrome.
PMID- 25119040
TI - Interacting supernovae from photoionization-confined shells around red supergiant
stars.
AB - Betelgeuse, a nearby red supergiant, is a fast-moving star with a powerful
stellar wind that drives a bow shock into its surroundings. This picture has been
challenged by the discovery of a dense and almost static shell that is three
times closer to the star than the bow shock and has been decelerated by some
external force. The two physically distinct structures cannot both be formed by
the hydrodynamic interaction of the wind with the interstellar medium. Here we
report that a model in which Betelgeuse's wind is photoionized by radiation from
external sources can explain the static shell without requiring a new
understanding of the bow shock. Pressure from the photoionized wind generates a
standing shock in the neutral part of the wind and forms an almost static,
photoionization-confined shell. Other red supergiants should have much more
massive shells than Betelgeuse, because the photoionization-confined shell traps
up to 35 per cent of all mass lost during the red supergiant phase, confining
this gas close to the star until it explodes. After the supernova explosion,
massive shells dramatically affect the supernova light curve, providing a natural
explanation for the many supernovae that have signatures of circumstellar
interaction.
PMID- 25119039
TI - Structural mechanism of glutamate receptor activation and desensitization.
AB - Ionotropic glutamate receptors are ligand-gated ion channels that mediate
excitatory synaptic transmission in the vertebrate brain. To gain a better
understanding of how structural changes gate ion flux across the membrane, we
trapped rat AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) and
kainate receptor subtypes in their major functional states and analysed the
resulting structures using cryo-electron microscopy. We show that transition to
the active state involves a 'corkscrew' motion of the receptor assembly, driven
by closure of the ligand-binding domain. Desensitization is accompanied by
disruption of the amino-terminal domain tetramer in AMPA, but not kainate,
receptors with a two-fold to four-fold symmetry transition in the ligand-binding
domains in both subtypes. The 7.6 A structure of a desensitized kainate receptor
shows how these changes accommodate channel closing. These findings integrate
previous physiological, biochemical and structural analyses of glutamate
receptors and provide a molecular explanation for key steps in receptor gating.
PMID- 25119038
TI - AhR sensing of bacterial pigments regulates antibacterial defence.
AB - The aryl hydrocarbon receptor (AhR) is a highly conserved ligand-dependent
transcription factor that senses environmental toxins and endogenous ligands,
thereby inducing detoxifying enzymes and modulating immune cell differentiation
and responses. We hypothesized that AhR evolved to sense not only environmental
pollutants but also microbial insults. We characterized bacterial pigmented
virulence factors, namely the phenazines from Pseudomonas aeruginosa and the
naphthoquinone phthiocol from Mycobacterium tuberculosis, as ligands of AhR. Upon
ligand binding, AhR activation leads to virulence factor degradation and
regulated cytokine and chemokine production. The relevance of AhR to host defence
is underlined by heightened susceptibility of AhR-deficient mice to both P.
aeruginosa and M. tuberculosis. Thus, we demonstrate that AhR senses distinct
bacterial virulence factors and controls antibacterial responses, supporting a
previously unidentified role for AhR as an intracellular pattern recognition
receptor, and identify bacterial pigments as a new class of pathogen-associated
molecular patterns.
PMID- 25119041
TI - Interleukin-22 alleviates metabolic disorders and restores mucosal immunity in
diabetes.
AB - The connection between an altered gut microbiota and metabolic disorders such as
obesity, diabetes, and cardiovascular disease is well established. Defects in
preserving the integrity of the mucosal barriers can result in systemic
endotoxaemia that contributes to chronic low-grade inflammation, which further
promotes the development of metabolic syndrome. Interleukin (IL)-22 exerts
essential roles in eliciting antimicrobial immunity and maintaining mucosal
barrier integrity within the intestine. Here we investigate the connection
between IL-22 and metabolic disorders. We find that the induction of IL-22 from
innate lymphoid cells and CD4(+) T cells is impaired in obese mice under various
immune challenges, especially in the colon during infection with Citrobacter
rodentium. While innate lymphoid cell populations are largely intact in obese
mice, the upregulation of IL-23, a cytokine upstream of IL-22, is compromised
during the infection. Consequently, these mice are susceptible to C. rodentium
infection, and both exogenous IL-22 and IL-23 are able to restore the mucosal
host defence. Importantly, we further unveil unexpected functions of IL-22 in
regulating metabolism. Mice deficient in IL-22 receptor and fed with high-fat
diet are prone to developing metabolic disorders. Strikingly, administration of
exogenous IL-22 in genetically obese leptin-receptor-deficient (db/db) mice and
mice fed with high-fat diet reverses many of the metabolic symptoms, including
hyperglycaemia and insulin resistance. IL-22 shows diverse metabolic benefits, as
it improves insulin sensitivity, preserves gut mucosal barrier and endocrine
functions, decreases endotoxaemia and chronic inflammation, and regulates lipid
metabolism in liver and adipose tissues. In summary, we identify the IL-22
pathway as a novel target for therapeutic intervention in metabolic diseases.
PMID- 25119042
TI - PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4
based therapies.
AB - The polycomb repressive complex 2 (PRC2) exerts oncogenic effects in many tumour
types. However, loss-of-function mutations in PRC2 components occur in a subset
of haematopoietic malignancies, suggesting that this complex plays a dichotomous
and poorly understood role in cancer. Here we provide genomic, cellular, and
mouse modelling data demonstrating that the polycomb group gene SUZ12 functions
as tumour suppressor in PNS tumours, high-grade gliomas and melanomas by
cooperating with mutations in NF1. NF1 encodes a Ras GTPase-activating protein
(RasGAP) and its loss drives cancer by activating Ras. We show that SUZ12 loss
potentiates the effects of NF1 mutations by amplifying Ras-driven transcription
through effects on chromatin. Importantly, however, SUZ12 inactivation also
triggers an epigenetic switch that sensitizes these cancers to bromodomain
inhibitors. Collectively, these studies not only reveal an unexpected connection
between the PRC2 complex, NF1 and Ras, but also identify a promising epigenetic
based therapeutic strategy that may be exploited for a variety of cancers.
PMID- 25119043
TI - Haematopoietic stem cell induction by somite-derived endothelial cells controlled
by meox1.
AB - Haematopoietic stem cells (HSCs) are self-renewing stem cells capable of
replenishing all blood lineages. In all vertebrate embryos that have been
studied, definitive HSCs are generated initially within the dorsal aorta (DA) of
the embryonic vasculature by a series of poorly understood inductive events.
Previous studies have identified that signalling relayed from adjacent somites
coordinates HSC induction, but the nature of this signal has remained elusive.
Here we reveal that somite specification of HSCs occurs via the deployment of a
specific endothelial precursor population, which arises within a sub-compartment
of the zebrafish somite that we have defined as the endotome. Endothelial cells
of the endotome are specified within the nascent somite by the activity of the
homeobox gene meox1. Specified endotomal cells consequently migrate and colonize
the DA, where they induce HSC formation through the deployment of chemokine
signalling activated in these cells during endotome formation. Loss of meox1
activity expands the endotome at the expense of a second somitic cell type, the
muscle precursors of the dermomyotomal equivalent in zebrafish, the external cell
layer. The resulting increase in endotome-derived cells that migrate to colonize
the DA generates a dramatic increase in chemokine-dependent HSC induction. This
study reveals the molecular basis for a novel somite lineage restriction
mechanism and defines a new paradigm in induction of definitive HSCs.
PMID- 25119044
TI - CRISPR-mediated direct mutation of cancer genes in the mouse liver.
AB - The study of cancer genes in mouse models has traditionally relied on genetically
engineered strains made via transgenesis or gene targeting in embryonic stem
cells. Here we describe a new method of cancer model generation using the
CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR
associated proteins) system in vivo in wild-type mice. We used hydrodynamic
injection to deliver a CRISPR plasmid DNA expressing Cas9 and single guide RNAs
(sgRNAs) to the liver that directly target the tumour suppressor genes Pten (ref.
5) and p53 (also known as TP53 and Trp53) (ref. 6), alone and in combination.
CRISPR-mediated Pten mutation led to elevated Akt phosphorylation and lipid
accumulation in hepatocytes, phenocopying the effects of deletion of the gene
using Cre-LoxP technology. Simultaneous targeting of Pten and p53 induced liver
tumours that mimicked those caused by Cre-loxP-mediated deletion of Pten and p53.
DNA sequencing of liver and tumour tissue revealed insertion or deletion
mutations of the tumour suppressor genes, including bi-allelic mutations of both
Pten and p53 in tumours. Furthermore, co-injection of Cas9 plasmids harbouring
sgRNAs targeting the beta-catenin gene and a single-stranded DNA oligonucleotide
donor carrying activating point mutations led to the generation of hepatocytes
with nuclear localization of beta-catenin. This study demonstrates the
feasibility of direct mutation of tumour suppressor genes and oncogenes in the
liver using the CRISPR/Cas system, which presents a new avenue for rapid
development of liver cancer models and functional genomics.
PMID- 25119046
TI - Promoter sequences direct cytoplasmic localization and translation of mRNAs
during starvation in yeast.
AB - A universal feature of the response to stress and nutrient limitation is
transcriptional upregulation of genes that encode proteins important for
survival. Under many such conditions, the overall protein synthesis level is
reduced, thereby dampening the stress response at the level of protein
expression. For example, during glucose starvation in Saccharomyces cerevisiae
(yeast), translation is rapidly repressed, yet the transcription of many stress-
and glucose-repressed genes is increased. Here we show, using ribosomal profiling
and microscopy, that this transcriptionally upregulated gene set consists of two
classes: one class produces messenger RNAs that are translated during glucose
starvation and are diffusely localized in the cytoplasm, including many heat
shock protein mRNAs; and the other class produces mRNAs that are not efficiently
translated during glucose starvation and are concentrated in foci that co
localize with P bodies and stress granules, a class that is enriched for mRNAs
involved in glucose metabolism. Surprisingly, the information specifying the
differential localization and protein production of these two classes of mRNA is
encoded in the promoter sequence: promoter responsiveness to heat-shock factor 1
(Hsf1) specifies diffuse cytoplasmic localization and higher protein production
on glucose starvation. Thus, promoter sequences can influence not only the levels
of mRNAs but also the subcellular localization of mRNAs and the efficiency with
which they are translated, enabling cells to tailor protein production to the
environmental conditions.
PMID- 25119045
TI - A long noncoding RNA protects the heart from pathological hypertrophy.
AB - The role of long noncoding RNA (lncRNA) in adult hearts is unknown; also unclear
is how lncRNA modulates nucleosome remodelling. An estimated 70% of mouse genes
undergo antisense transcription, including myosin heavy chain 7 (Myh7), which
encodes molecular motor proteins for heart contraction. Here we identify a
cluster of lncRNA transcripts from Myh7 loci and demonstrate a new lncRNA
chromatin mechanism for heart failure. In mice, these transcripts, which we named
myosin heavy-chain-associated RNA transcripts (Myheart, or Mhrt), are cardiac
specific and abundant in adult hearts. Pathological stress activates the Brg1
Hdac-Parp chromatin repressor complex to inhibit Mhrt transcription in the heart.
Such stress-induced Mhrt repression is essential for cardiomyopathy to develop:
restoring Mhrt to the pre-stress level protects the heart from hypertrophy and
failure. Mhrt antagonizes the function of Brg1, a chromatin-remodelling factor
that is activated by stress to trigger aberrant gene expression and cardiac
myopathy. Mhrt prevents Brg1 from recognizing its genomic DNA targets, thus
inhibiting chromatin targeting and gene regulation by Brg1. It does so by binding
to the helicase domain of Brg1, a domain that is crucial for tethering Brg1 to
chromatinized DNA targets. Brg1 helicase has dual nucleic-acid-binding
specificities: it is capable of binding lncRNA (Mhrt) and chromatinized--but not
naked--DNA. This dual-binding feature of helicase enables a competitive
inhibition mechanism by which Mhrt sequesters Brg1 from its genomic DNA targets
to prevent chromatin remodelling. A Mhrt-Brg1 feedback circuit is thus crucial
for heart function. Human MHRT also originates from MYH7 loci and is repressed in
various types of myopathic hearts, suggesting a conserved lncRNA mechanism in
human cardiomyopathy. Our studies identify a cardioprotective lncRNA, define a
new targeting mechanism for ATP-dependent chromatin-remodelling factors, and
establish a new paradigm for lncRNA-chromatin interaction.
PMID- 25119047
TI - Jam1a-Jam2a interactions regulate haematopoietic stem cell fate through Notch
signalling.
AB - Notch signalling plays a key role in the generation of haematopoietic stem cells
(HSCs) during vertebrate development and requires intimate contact between signal
emitting and signal-receiving cells, although little is known regarding when,
where and how these intercellular events occur. We previously reported that the
somitic Notch ligands, Dlc and Dld, are essential for HSC specification. It has
remained unclear, however, how these somitic requirements are connected to the
later emergence of HSCs from the dorsal aorta. Here we show in zebrafish that
Notch signalling establishes HSC fate as their shared vascular precursors migrate
across the ventral face of the somite and that junctional adhesion molecules
(JAMs) mediate this required Notch signal transduction. HSC precursors express
jam1a (also known as f11r) and migrate axially across the ventral somite, where
Jam2a and the Notch ligands Dlc and Dld are expressed. Despite no alteration in
the expression of Notch ligand or receptor genes, loss of function of jam1a led
to loss of Notch signalling and loss of HSCs. Enforced activation of Notch in
shared vascular precursors rescued HSCs in jam1a or jam2a deficient embryos.
Together, these results indicate that Jam1a-Jam2a interactions facilitate the
transduction of requisite Notch signals from the somite to the precursors of
HSCs, and that these events occur well before formation of the dorsal aorta.
PMID- 25119049
TI - Gradual unlocking of plate boundary controlled initiation of the 2014 Iquique
earthquake.
AB - On 1 April 2014, Northern Chile was struck by a magnitude 8.1 earthquake
following a protracted series of foreshocks. The Integrated Plate Boundary
Observatory Chile monitored the entire sequence of events, providing
unprecedented resolution of the build-up to the main event and its rupture
evolution. Here we show that the Iquique earthquake broke a central fraction of
the so-called northern Chile seismic gap, the last major segment of the South
American plate boundary that had not ruptured in the past century. Since July
2013 three seismic clusters, each lasting a few weeks, hit this part of the plate
boundary with earthquakes of increasing peak magnitudes. Starting with the second
cluster, geodetic observations show surface displacements that can be associated
with slip on the plate interface. These seismic clusters and their slip
transients occupied a part of the plate interface that was transitional between a
fully locked and a creeping portion. Leading up to this earthquake, the b value
of the foreshocks gradually decreased during the years before the earthquake,
reversing its trend a few days before the Iquique earthquake. The mainshock
finally nucleated at the northern end of the foreshock area, which skirted a
locked patch, and ruptured mainly downdip towards higher locking. Peak slip was
attained immediately downdip of the foreshock region and at the margin of the
locked patch. We conclude that gradual weakening of the central part of the
seismic gap accentuated by the foreshock activity in a zone of intermediate
seismic coupling was instrumental in causing final failure, distinguishing the
Iquique earthquake from most great earthquakes. Finally, only one-third of the
gap was broken and the remaining locked segments now pose a significant,
increased seismic hazard with the potential to host an earthquake with a
magnitude of >8.5.
PMID- 25119048
TI - X-ray structure of the mouse serotonin 5-HT3 receptor.
AB - Neurotransmitter-gated ion channels of the Cys-loop receptor family mediate fast
neurotransmission throughout the nervous system. The molecular processes of
neurotransmitter binding, subsequent opening of the ion channel and ion
permeation remain poorly understood. Here we present the X-ray structure of a
mammalian Cys-loop receptor, the mouse serotonin 5-HT3 receptor, at 3.5 A
resolution. The structure of the proteolysed receptor, made up of two fragments
and comprising part of the intracellular domain, was determined in complex with
stabilizing nanobodies. The extracellular domain reveals the detailed anatomy of
the neurotransmitter binding site capped by a nanobody. The membrane domain
delimits an aqueous pore with a 4.6 A constriction. In the intracellular domain,
a bundle of five intracellular helices creates a closed vestibule where lateral
portals are obstructed by loops. This 5-HT3 receptor structure, revealing part of
the intracellular domain, expands the structural basis for understanding the
operating mechanism of mammalian Cys-loop receptors.
PMID- 25119051
TI - Comment on: editorial by Husted et al. "Non-vitamin K antagonist oral
anticoagulants (NOACs): no longer new or novel". (Thromb Haemost 2014; 111: 781
782).
PMID- 25119050
TI - Protein competition switches the function of COP9 from self-renewal to
differentiation.
AB - The balance between stem cell self-renewal and differentiation is controlled by
intrinsic factors and niche signals. In the Drosophila melanogaster ovary, some
intrinsic factors promote germline stem cell (GSC) self-renewal, whereas others
stimulate differentiation. However, it remains poorly understood how the balance
between self-renewal and differentiation is controlled. Here we use D.
melanogaster ovarian GSCs to demonstrate that the differentiation factor Bam
controls the functional switch of the COP9 complex from self-renewal to
differentiation via protein competition. The COP9 complex is composed of eight
Csn subunits, Csn1-8, and removes Nedd8 modifications from target proteins.
Genetic results indicated that the COP9 complex is required intrinsically for GSC
self-renewal, whereas other Csn proteins, with the exception of Csn4, were also
required for GSC progeny differentiation. Bam-mediated Csn4 sequestration from
the COP9 complex via protein competition inactivated the self-renewing function
of COP9 and allowed other Csn proteins to promote GSC differentiation. Therefore,
this study reveals a protein-competition-based mechanism for controlling the
balance between stem cell self-renewal and differentiation. Because numerous self
renewal factors are ubiquitously expressed throughout the stem cell lineage in
various systems, protein competition may function as an important mechanism for
controlling the self-renewal-to-differentiation switch.
PMID- 25119052
TI - Does proximal tibial osteotomy with a novel osteotomy system obtain coronal plane
correction without affecting tibial slope and patellar height?
AB - PURPOSE: To determine changes in tibial slope, patellar height, and coronal plane
alignment after medial opening wedge proximal tibial osteotomy (PTO) using a
modern osteotomy system. METHODS: Patients undergoing medial opening wedge PTO
for any indication with follow-up until radiographic union were identified. Pre-
and post-operative tibial slope (referenced off the anterior tibial cortex,
proximal tibial anatomic axis, and posterior tibial cortex), patellar height
(Caton-Deschamps, Blackburne-Peel, and Insall-Salvati indices), and coronal plane
[mechanical axis and weight-bearing line (WBL) ratio] measurements were taken by
two observers and compared. RESULTS: Review of 27 patients demonstrated unchanged
tibial slope and slightly decreased patellar height post-operatively (Caton
Deschamps: -0.10 +/- 0.09; Blackburne-Peel: -0.11 +/- 0.10). Coronal plane
measurements showed 6.4 degrees +/- 1.8 degrees mean change in mechanical axis.
Mean post-operative WBL ratio was significantly lower (51.6 +/- 11.5 %) than mean
goal WBL ratio (62.2 +/- 2.5 %). Preoperative mechanical axis >6 degrees varus
and osteoarthritis alone as the surgical indication were risk factors for
undercorrection >10 %. CONCLUSIONS: Medial opening wedge PTO using a recently
developed instrumentation system was found to have no effect on tibial slope.
Patellar height was decreased after osteotomy using this system, although
clinical significance of these findings is unknown. Coronal plane undercorrection
of 10.6 % of the target WBL ratio was seen in the group as a whole, although
secondary analysis of these results indicated that patients with medial
compartment osteoarthritis and/or preoperative mechanical axis of >6 degrees
varus accounted for the majority of the cases of undercorrection. LEVEL OF
EVIDENCE: Retrospective case series, Level IV.
PMID- 25119053
TI - Retention of the posterior cruciate ligament does not affect femoral rotational
alignment in TKA using a gap-balance technique.
AB - PURPOSE: Previous studies have evaluated the ability of the gap technique to
achieve accurate rotational placement in both posterior cruciate ligament (PCL)
retaining and PCL-substituting total knee arthroplasty (TKA). The purpose of the
present study was to determine (1) the accuracy of this technique in degrees and
(2) whether retention of the PCL affects the rotational alignment of the femoral
component relative to the transepicondylar axis during TKA. The hypothesis of
this study was that retention of the PCL does not affect the femoral rotational
alignment in TKA using a gap-balancing technique because both procedures are
reported to have good long-term clinical outcomes. METHODS: The femoral rotation
angle (FRA) relative to the transepicondylar axis was examined in 206 patients
who underwent primary TKA using either PCL-retaining (104 knees) or PCL
substituting (102 knees) prostheses to determine the effect of PCL retention on
FRA. Quantitative three-dimensional computed tomography was used to assess the
FRA in both groups. All values are expressed as median (25th percentile, 75th
percentile). RESULTS: Postoperative FRA in the PCL-retaining group was -1.1
degrees (-2.8 degrees , 2.2 degrees ) and in the PCL-substituting group was -0.1
degrees (-2.5 degrees , 2.8 degrees ). The groups were not statistically
different. One outlier was found in the PCL-retaining group, and none was found
in the PCL-substituting group. CONCLUSIONS: The gap technique reliably allows
accurate rotational alignment of the femoral component during TKA despite the
retention of the PCL. LEVEL OF EVIDENCE: Therapeutic study, Level II.
PMID- 25119054
TI - Comparison of the outcome of early and delayed surgical treatment of complete
acromioclavicular joint dislocation.
AB - PURPOSE: The aim of this study is to compare the clinical and radiographic
results and the complication rate between early and delayed surgical treatment of
acromioclavicular joint (ACJ) dislocation. METHODS: Publications in the
management of ACJ dislocation are identified from the PubMed database between
January 1993 and December 2013 using "acromioclavicular joint" and "dislocation"
as keywords. The eligibility criteria included are as follows: (1) ACJ
dislocation; (2) intervention, early compared with delayed surgical treatment or
the surgical treatment for acute compared with chronic ACJ dislocation; (3)
human; and (4) English articles. Exclusion criteria consist of the following: (1)
type I and type II ACJ dislocation, (2) no definition of the time of early and
delayed surgery in studies, (3) no comparison between the clinical result of
early and delayed surgery in studies, (4) laboratory studies, radiographic
studies, biomechanical studies, (5) the cases including fractures or revisions in
studies, and (6) systematic analyses. RESULTS: Eight studies comparing early and
delayed surgical treatment of ACJ dislocation are included in this systematic
review. According to Constant scores and shoulder subjective value, early surgery
has better functional outcomes than delayed surgery in the treatment of ACJ
dislocation (P < 0.05). Partial-dislocation/re-dislocation is found at 26.0 % in
early and 38.1 % in delayed surgical treatment (P < 0.05). The rate of CC
ossification in early surgical treatment is found as the same as the delayed. The
complication rates are found at 12.5 % in early surgical treatment and 17.7 % in
the delayed, which is not significantly different. CONCLUSION: Early surgical
treatment may have superiority to the delayed procedure in the management of ACJ
dislocation with better functional outcomes and more satisfied reduction.
However, high-quality evidence studies are required to provide stronger support
for this opinion in the future. LEVEL OF EVIDENCE: IV.
PMID- 25119055
TI - Radiological outcomes of pinless navigation in total knee arthroplasty: a
randomized controlled trial.
AB - PURPOSE: This study aimed to investigate the accuracy of pinless navigation
(BrainLAB((r)) VectorVision((r)) Knee 2.5 Navigation System) as an intra
operative alignment guide in total knee arthroplasty (TKA). The authors
hypothesized that pinless navigation would reduce the proportion of outliers in
conventional TKA, without a significant increase in the duration of surgery.
METHODS: Between 2011 and 2012, 100 patients scheduled for a unilateral primary
TKA were randomized into two groups: pinless navigation and conventional surgery.
All TKAs were performed with the surgical aim of achieving neutral coronal
alignment with a 180 degrees mechanical axis. The primary outcomes of this study
were post-operative radiographic assessment of lower limb alignment using hip
knee-ankle angle (HKA) and components placement using coronal femoral-component
angle (CFA) and coronal tibia-component angle (CTA). RESULTS: There was a smaller
proportion of outliers for HKA, CFA and CTA at 10, 2 and 2 % respectively, in the
pinless navigation group, compared to 32, 16 and 16 %, respectively, in the
conventional group (p = 0.013, p = 0.032 and p = 0.032, respectively). The mean
CFA was also more accurate at 90 degrees in the pinless navigation group
compared to 91 degrees in the conventional group (p = 0.002). There was no
difference in the duration of surgery between the two groups (n.s.). CONCLUSIONS:
Pinless navigation improves lower limb alignment and components placement without
a significant increase in the duration of surgery. The authors recommend the use
of pinless navigation to verify the coronal alignments of conventional cutting
blocks in TKA before the bone cuts are made. LEVEL OF EVIDENCE: I.
PMID- 25119056
TI - Development of a brief substance use sensation seeking scale: validation and
prediction of injection-related behaviors.
AB - Sensation seeking, a personality trait, has been shown to predict engagement in
high-risk behaviors. However, little is known regarding the impact of sensation
seeking on substance use among street youth. We therefore sought to modify a
sensation seeking scale (SSS) for use among this population. Street youth from
the Vancouver-based At-Risk Youth Study (n = 226) completed the modified SSS.
Exploratory and confirmatory factor analysis (EFA/CFA) were undertaken to
establish the scale's dimensionality and internal validity. The association
between SSS score and injection-related behaviors was tested using generalized
estimating equation analysis. EFA results indicated scale unidimensionality. The
comparative fit index (CFI) suggested acceptable fit (CFI = 0.914). In
multivariate analysis, sensation seeking was independently associated with
injection drug use, crystal methamphetamine use, polysubstance use, and binge
drug use (all p < 0.05). Our findings provide preliminary support for the use of
the modified SSS among street youth.
PMID- 25119058
TI - Can the immunological response to botulinum toxin trigger headaches?
AB - OnabotulinumtoxinA has recently proved beneficial for the treatment of chronic
migraine; even though, headaches are not infrequently reported by patients
receiving botulinum toxins for different conditions. Here the author discusses
the potential mechanisms on how the immunological response following the
application of botulinum toxins may trigger headaches and/or migraine.
PMID- 25119060
TI - Kanglaite stimulates anticancer immune responses and inhibits HepG2 cell
transplantation-induced tumor growth.
AB - Previous studies revealed that Kanglaite (KLT) exhibits antitumor and
immunomodulatory activities. In the present study, we show that KLT treatment
stimulated the immune response by increasing the number of T cells and natural
killer (NK) cells in the blood of hepatocellular carcinoma (HCC) patients.
Experiments in tumor-bearing mice were further designed in order to explore the
effects of KLT on the immune system and the underlying molecular mechanisms. The
results showed that KLT improves the tumor cell transplantation-induced reduction
in the serum level of the cytokines IFN-gamma and IL-2, and rescues the levels of
CD4+ T cells in host mice. These events enhanced the cytotoxic activities of
natural killer and CD8+ T cells against the hepatic HepG2 cancer cells. KLT
administration further increased the mRNA level of certain nuclear factor kappaB
(NF-kappaB)-responsive genes in CD4+ cells. The chromatin immunoprecipitation
assay showed that KLT increases the association of the NF-kappaB p65 subunit to
the promoter regions of interleukin (IL)-2- and B-cell lymphoma (Bcl)-2-encoding
genes in CD4+ T cells. Our study demonstrated that KLT is the main active
ingredient of coix seed exhibiting anticancer and immunomodulatory properties.
Induction of NF-kappaB-mediated gene transcription in CD4+ T cells is involved in
the immunomodulatory activity of KLT.
PMID- 25119059
TI - Novel mechanism of intra-renal angiotensin II-induced sodium/proton exchanger 3
expression by losartan in spontaneously hypertensive rats.
AB - The present study aimed to investigate the molecular pharmacodynamic mechanisms
of losartan used in the treatment of hypertension. A total of 12 spontaneously
hypertensive rats (SHR) were divided randomly into an SHR group treated with
saline and LOS group treated with losartan. Six Wistar-kyoto rats (WKY) were
enrolled as the WKY group with saline in the study. The LOS group received 30
mg/kg/day losartan by intragastric injection, while the SHR and WKY were fed the
same volume of saline. The dosage was modulated according to the weekly weight.
Changes in blood pressure were measured by the indirect tail cuff method.
Angiotensin (Ang) II production in the plasma and renal tissue was measured by an
immunoradiometric method. Na+/H+ exchanger (NHE)3 and serum and glucocorticoid
inducible kinase (SGK)1 were assessed by quantitative polymerase chain reaction
(qPCR) and western blot analysis. When compared with the WKY group, the blood
pressure of the SHR and LOS groups were higher prior to treatment with losartan.
Following two weeks, blood pressure was reduced and the trend continued to
decrease over the following six weeks. The plasma and renal tissue levels of Ang
II in the SHR and LOS groups were significantly higher than those in the WKY
group. NHE3 and SGK1 were increased at the mRNA and protein level in the SHR
group, and losartan reduced the expression of both of them. The results suggested
that in hypertensive rats, the circular and tissue renin angiotensin systems were
activated, and the increased Ang II stimulated the expression of NHE3 and SGK1,
which was reduced by losartan. Therefore, the effects of losartan in hypertension
may be associated with the Ang II-SGK1-NHE3 of intra-renal tissue.
PMID- 25119061
TI - The expression of glucagon-like peptide-1 receptor and dipeptidyl peptidase-IV in
neuroendocrine neoplasms of the pancreas and gastrointestinal tract.
AB - Neuroendocrine neoplasm (NEN) of the pancreas and gastrointestinal tract is
infrequent but often produces hormones to cause distinct clinical features.
Glucagon-like peptide-1 receptor (GLP1R) is a G-protein coupled receptor for
GLP1, which is cleaved by dipeptidyl peptidase (DPP)-IV, a peptidase that
regulates the activity of peptide hormones. Since these molecules are involved in
the neuroendocrine function of NEN, they could serve molecular targets for
diagnosis and therapy of NEN. However, the expressions of these molecules in NEN
are not well studied. We therefore examined the expression of GLP1R and DPP-IV in
22 cases of pancreatic NEN (P-NEN) and 20 cases of gastrointestinal NEN (GI-NEN)
by immunostaining. GLP1R was expressed in all eight insulinomas (100 %) but so in
only four out of 14 cases (29 %) of non-insulinomas. In contrast to GLP1R, DPP-IV
was detected in one out of eight insulinomas (13 %) and in 12 out of 14 cases (86
%) of non-insulinomas. In GI-NEN, GLP1R was negative in all 10 cases of the
foregut NEN, whereas it was expressed in all three cases (100 %) of midgut NEN
and four out of seven cases (57 %) of hindgut NEN. DPP-IV was expressed in five
out of 10 cases (50 %) of the foregut NEN. The expression was detected in two out
of three cases (67 %) of midgut NEN and in all seven cases (100 %) of hindgut
NEN. In conclusion, we found distinct expression patterns of GLP1R and DPP-IV
depending on the neuroendocrine cell types in P-NEN and the anatomical sites in
GI-NEN.
PMID- 25119062
TI - Nintedanib for the treatment of patients with advanced non-small-cell lung
cancer.
AB - An unmet need remains for effective, well-tolerated treatment options in advanced
non-small-cell lung cancer that can alleviate the disease burden for a broad
selection of patients. Nintedanib (Vargatef) is a potent, oral, triple
angiokinase inhibitor of three distinct pro-angiogenic pathways. A recent Phase
III trial of second-line nintedanib plus docetaxel met the primary end point of
progression-free survival and demonstrated significant benefit in the key
secondary end point of overall survival, with median overall survival greater
than 1 year for patients with adenocarcinoma histology. This article summarizes
preclinical and clinical experience with nintedanib in non-small-cell lung cancer
to date and discusses how it may be used in the future, including prospects for
individualizing treatment by tumor proliferation dynamics and molecular
biomarkers of response.
PMID- 25119063
TI - Effect of iDose4 iterative reconstruction algorithm on image quality and
radiation exposure in prospective and retrospective electrocardiographically
gated coronary computed tomographic angiography.
AB - OBJECTIVES: The aims of this study were to compare a commercially available
reconstruction algorithm (iDose4) with filtered back projection (FBP) in terms of
image quality (IQ) for both retrospective electrocardiographically gated and
prospective electrocardiographically triggered cardiac computed tomographic
angiography (CCTA) protocols and to evaluate the achievable radiation dose
reduction. METHODS: A total cohort of 58 patients underwent either prospective
CTCA or retrospective CTCA with full or reduced tube current-time product (in
milliampere-second) protocol on a 64-slice multidetector computed tomographic
scanner. All images were reconstructed with FBP, whereas the reduced milliampere
second images were also reconstructed using 2 levels (levels 4 and 6) of iDose4.
Subjective and objective IQ was evaluated. RESULTS: Dose reductions of 43% in the
retrospective CCTA protocol and 27% in the prospective CCTA protocol were
achieved without compromising IQ. In the prospective CCTA protocol, the reduced
dose images were highly scored; thus, additional reduction of exposure settings
is feasible. In the retrospective acquisition, dose reduction has led to similar
IQ scores between the reduced-dose iDose4 images and the full-dose FBP images.
Considering different reconstructions (FBP, iDose-L4 and -L6) of the same
acquisition data, increase in iDose4 level resulted in less noisy images. A
slight improvement was also noticed in all IQ indices; however, this improvement
was not statistically significant for both acquisition protocols. CONCLUSIONS:
This study demonstrated that the application of iDose at CCTA facilitates
significant radiation dose reduction by maintaining diagnostic quality. The
combination of iDose4 with prospective acquisition is able to significantly
reduce effective dose associated with CTCA at values of approximately 2 mSv and
even lower.
PMID- 25119064
TI - Choosing the best reconstruction technique in abdominal computed tomography: a
systematic approach.
AB - OBJECTIVE: There is uncertainty regarding the effect of iterative reconstruction
(IR) techniques and other reconstruction algorithms on image quality. The aim of
this study was to optimize image quality in relation to radiation dose in
computed tomography (CT) liver examinations by comparing images reconstructed
with different abdominal filters with and without IR. METHODS: An anthropomorphic
phantom was scanned on a Toshiba Aquilion ONE CT scanner. Images at 2 different
dose levels were reconstructed with 12 different body reconstruction filters, all
with both filtered back-projection and Adaptive Iterative Dose Reduction 3
dimensional. Receiver operating characteristic curves were constructed. The 2
reconstruction combinations with the highest scores from the phantom study were
evaluated in a second comparison of clinical images. Six liver examinations were
reconstructed with both filters and evaluated using visual grading analysis.
RESULTS: Two combinations of reconstruction filters and IR were the only 2
options among the 8 best images at both dose levels (area under the curve, 0.96
and 0.94 for 15 mGy as well as 0.86 and 0.84 for 10 mGy). In the patient study,
one of these filters in combination with IR scored slightly higher than the other
in combination with IR (mean score, 2.60 and 2.57, respectively; P = 0.56).
Iterative reconstruction did not significantly increase lesion detectability for
any of the filters. CONCLUSIONS: This study indicates that the preferred choice
for reconstruction of CT liver examinations performed with the Toshiba Aquilion
ONE should be the FC18 filter with IR, although the IR technique did not
significantly improve lesion detectability and did not compensate for the dose
reduction in this study.
PMID- 25119065
TI - Computed tomography imaging manifestations of commonly used materials in
posttraumatic craniofacial repair.
AB - An expansive array of materials exists within the armamentarium of craniofacial
surgeons. For patients undergoing repair of posttraumatic injuries, computed
tomography is the imaging modality of choice in the postoperative setting.
Therefore, radiologists will invariably encounter implants constructed with
various materials, depending on the surgeon's preference. The appearance of these
materials on computed tomography is broad, ranging from hyperdense to
radiolucent. To avoid misdiagnosis, radiologists should be familiar with all of
the materials currently in use.
PMID- 25119066
TI - Perceptions of users and providers on barriers to utilizing skilled birth care in
mid- and far-western Nepal: a qualitative study.
AB - BACKGROUND: Although skilled birth care contributes significantly to the
prevention of maternal and newborn morbidity and mortality, utilization of such
care is poor in mid- and far-western Nepal. This study explored the perceptions
of service users and providers regarding barriers to skilled birth care. DESIGN:
We conducted 24 focus group discussions, 12 each with service users and service
providers from different health institutions in mid- and far-western Nepal. All
discussions examined the perceptions and experiences of service users and
providers regarding barriers to skilled birth care and explored possible
solutions to overcoming such barriers. RESULTS: Our results determined that major
barriers to skilled birth care include inadequate knowledge of the importance of
services offered by skilled birth attendants (SBAs), distance to health
facilities, unavailability of transport services, and poor availability of SBAs.
Other barriers included poor infrastructure, meager services, inadequate
information about services/facilities, cultural practices and beliefs, and low
prioritization of birth care. Moreover, the tradition of isolating women during
and after childbirth decreased the likelihood that women would utilize delivery
care services at health facilities. CONCLUSIONS: Service users and providers
perceived inadequate availability and accessibility of skilled birth care in
remote areas of Nepal, and overall utilization of these services was poor.
Therefore, training and recruiting locally available health workers, helping
community groups establish transport mechanisms, upgrading physical facilities
and services at health institutions, and increasing community awareness of the
importance of skilled birth care will help bridge these gaps.
PMID- 25119069
TI - Coping with the longevity revolution.
PMID- 25119067
TI - A novel Interactive Health Communication Application (IHCA) for parents of
children with long-term conditions: Development, implementation and feasibility
assessment.
AB - BACKGROUND: Few evidence-based, on-line resources exist to support home-based
care of childhood long-term conditions. METHODS: In a feasibility study, children
with stages 3, 4, or 5 chronic kidney disease, parents and professionals
collaboratively developed a novel Online Parent Information and Support (OPIS)
application. Parents were randomized to an intervention arm with access to OPIS
or a control arm without access. OPIS usage was assessed using Google Analytics.
Parents in the intervention arm completed the Suitability Assessment of Materials
(SAM) and User Interface Satisfaction (USE) questionnaires and participated in
qualitative interviews. RESULTS: Twenty parents accessed OPIS with a mean of 23.3
(SD 20.8, range 2-64) visits per user. Responses from the SAM and USE
questionnaires were positive, most respondents rating OPIS highly and finding it
easy to use. Qualitative suggestions include refinement of OPIS components,
enabling personalization of OPIS functionalities and proactive endorsements of
OPIS by professionals. CONCLUSIONS: Implementation of OPIS into standard practice
is feasible in the centre where it was developed. Suggested developments will
augment reported strengths to inform ongoing testing in the wider UK network of
units. Our design and methods are transferrable to developing and evaluating web
applications to support home-based clinical care-giving for other long-term
conditions.
PMID- 25119070
TI - [Significances of the life experience for the long-lived elderly person in the
process of death/dying and mourning].
AB - This is a study using the Heideggerian theoretical-phenomenological approach,
which sought to understand the significances of the life experience for the long
lived elderly person in the process of death/dying and mourning. It was conducted
in 2009 with 16 long-lived senior citizens of both genders who were aged between
80 and 90, members of a community center for the elderly located in a suburban
neighborhood of the city of Salvador in the state of Bahia, Brazil. The results
showed that the long-lived elderly person experiences the mourning status process
when relatives and friends become ill and die. Furthermore, they gave ambiguous
reports with respect to the fear of death. With the attributed significances, it
was possible to arrive at the unit of significance, namely the authenticity and
lack of authenticity of the individual regarding imminent death. The conclusion
reached is that long-lived elderly individuals faced with the process of
death/dying and mourning is apparent or concealed in accordance with the moment
they are experiencing and the opportunities that present themselves, in other
words, it is greatly influenced by their past.
PMID- 25119068
TI - Attention-deficit/hyperactivity disorder and risk for drug use disorder: a
population-based follow-up and co-relative study.
AB - BACKGROUND: Although the association between attention-deficit/hyperactivity
disorder (ADHD) and drug use disorder (DUD) is well documented, it is unclear
whether it is causal or results from familial confounding. METHOD: In this study
we included all 551 164 individuals born in Sweden between 1991 and 1995 and used
linked data from multiple nationwide registries to identify those with ADHD prior
to age 15 years (1.71%). We used Cox proportional hazards models to investigate
the future risk for DUD as a function of an ADHD registration and then compared
the results from the entire population with the results from a co-relative
design. Using the Swedish Multi-Generation Register, we identified all full
sibling, half-sibling and first-cousin pairs discordant for ADHD. RESULTS: In the
population sample, ADHD had a substantially increased risk for future DUD with a
hazard ratio (HR) of 3.34 after accounting for gender and parental education.
Examining discordant cousin pairs, discordant half-siblings and discordant
siblings, those with ADHD had HRs for DUD of 3.09, 2.10 and 2.38 respectively.
Controlling for the number of ADHD registrations, ADHD patients with and without
stimulant treatment were similarly associated with later DUD risk. CONCLUSIONS:
ADHD diagnosed before 15 years of age was strongly related to future risk for
DUD. The magnitude of this association was modestly reduced in relative pairs
discordant for ADHD, suggesting that the ADHD-DUD association is partly causal
and partly a result of familial confounding. We found no evidence to suggest that
this association resulted from stimulant treatment.
PMID- 25119057
TI - Mutational consequences of aberrant ion channels in neurological disorders.
AB - Neurological channelopathies are attributed to aberrant ion channels affecting
CNS, PNS, cardiac, and skeletal muscles. To maintain the homeostasis of excitable
tissues, functional ion channels are necessary to rely electrical signals,
whereas any malfunctioning serves as an intrinsic factor to develop neurological
channelopathies. Molecular basis of these disease is studied based on genetic and
biophysical approaches, e.g., loci positional cloning, whereas pathogenesis and
bio-behavioral analysis revealed the dependency on genetic mutations and inter
current triggering factors. Although electrophysiological studies revealed the
possible mechanisms of diseases, analytical study of ion channels remained
unsettled and therefore underlying mechanism in channelopathies is necessary for
better clinical application. Herein, we demonstrated (i) structural and
functional role of various ion channels (Na(+), K(+), Ca(2+),Cl(-)), (ii)
pathophysiology involved in the onset of their associated channelopathies, and
(iii) comparative sequence and phylogenetic analysis of diversified sodium,
potassium, calcium, and chloride ion channel subtypes.
PMID- 25119071
TI - [Evaluation of the functional capacity of the elderly and factors associated with
disability].
AB - The scope of this study was to evaluate the functional capacity and analyze the
characteristics associated with the disability of elderly individuals attended in
a Family Health Strategy Unit in Montes Claros in the state of Minas Gerais. The
Lawton and Brody scale and the Katz scale were used and then analyzed using
multinomial logistic regression. 286 elderly individuals were interviewed with
ages ranging from 60 to 103 years and a mean age of 71.2 years (SD +/- 8.3). Of
these, 61.9% self-reported their independence in terms of functional capacity.
The dependence only in IADL was positively associated with age >= 75 years (OR =
8.38), female gender (OR = 3.64) and heart disease (OR = 3.24). The dependence in
IADL and ADL was positively associated with age >= 75 years (OR = 6.40), without
a partner (OR = 3.26), those who had had a stroke (OR = 51.85), heart disease (OR
= 4.18) and diabetes (OR = 3.35). The highest proportion of elderly was
considered independent to carry out basic and instrumental activities of daily
living. However, a significant portion still has impaired functional status. It
is essential that the teams of the Family Health Strategy strive for health
promotion and disease prevention, and therapeutic interventions that can minimize
the factors that influence functional capacity.
PMID- 25119072
TI - Effect of the elimination of chronic diseases on disability-free life expectancy
among elderly individuals in Sao Paulo, Brazil, 2010.
AB - The scope of this study was to establish whether the elimination of certain
chronic diseases is capable of leading to the compression of morbidity among
elderly individuals in Sao Paulo (Brazil), 2010. A population-based, cross
sectional study was carried out with official data for the city of Sao Paulo
(Brazil) in 2010 and data from the SABE (Health, Wellbeing and Ageing) study. A
total of 907 elderly individuals were evaluated, 640 of whom were women (64.6%).
Sullivan's method was used for the calculation of disability-free life expectancy
(DFLE). Life tables for cause elimination were used to calculate the
probabilities of death with the elimination of health conditions. In absolute
terms, the gains in LE and DFLE were greater in the younger age group (60 to 74
years) in both genders. In relative terms (%DFLE in LE), the gains were higher
among women aged 75 years or older and among men aged 60 years. If eliminated,
heart disease was the condition that would most lead to the compression of
morbidity in both genders. The elimination of chronic diseases from the elderly
population could lead to a compression of morbidity in men and women at both 60
years of age and 75 years of age or older.
PMID- 25119073
TI - [Influence of voice and hearing changes in the quality of life of active elderly
individuals].
AB - This article seeks to verify the self-rated impact of voice and hearing changes
of active elderly individuals in their daily lives, and the influence of this
self-rating on quality of life. A cross-sectional study was conducted with 72
elderly individuals of an Open University for Senior Citizens in the state of Sao
Paulo. The questionnaires applied were HHIE-S; VHI and WHOQoL-Old. The Pearson
correlation coefficient was used adopting a p-level significance value of < 0.05.
The impact of hearing difficulties on daily life was perceived by 45.8%, and
moderate or severe voice handicap by 9.7% of the elderly individuals. The self
rating of hearing impact on daily life was correlated with the voice handicap
index. Quality of life was negatively affected by the increase in self-rating of
hearing and voice difficulties in daily life. The sample profile is typical of
successful aging with the acceptance of aging changes and consequently less
impact on daily lives than expected. The findings suggest that there is an impact
of voice and hearing handicap on quality of life, although it has revealed high
indices, bolstering the characteristic of adaptation of the sample to aging. The
results justify the need for improving actions of self-care and empowerment for
the elderly.
PMID- 25119074
TI - [Gait speed, grip strength and self-rated health among the elderly: data from the
FIBRA Campinas network, Sao Paulo, Brazil].
AB - The article seeks to investigate patterns of performance and relationships
between grip strength, gait speed and self-rated health, and investigate the
relationships between them, considering the variables of gender, age and family
income. This was conducted in a probabilistic sample of community-dwelling
elderly aged 65 and over, members of a population study on frailty. A total of
689 elderly people without cognitive deficit suggestive of dementia underwent
tests of gait speed and grip strength. Comparisons between groups were based on
low, medium and high speed and strength. Self-related health was assessed using a
5-point scale. The males and the younger elderly individuals scored significantly
higher on grip strength and gait speed than the female and oldest did; the
richest scored higher than the poorest on grip strength and gait speed; females
and men aged over 80 had weaker grip strength and lower gait speed; slow gait
speed and low income arose as risk factors for a worse health evaluation. Lower
muscular strength affects the self-rated assessment of health because it results
in a reduction in functional capacity, especially in the presence of poverty and
a lack of compensatory factors.
PMID- 25119075
TI - [Drug prescriptions of patients treated in a geriatric outpatient ward of a
university hospital: a descriptive cross-sectional study].
AB - The scope of this study was to evaluate drug prescriptions for elderly patients
in the geriatric outpatient ward of a hospital. A cross-sectional descriptive
study was conducted in a university hospital, with the application of a
questionnaire. Patients aged >60 years were interviewed about their drug
prescriptions and a total of 208 patients were interviewed. The average number of
drugs used per person was 3.8 and the drugs most used were for the cardiovascular
system (37%). 406 potential interactions were identified in 140 patients (67.3%),
and duplicate therapy was found in two prescriptions. The potentially
inappropriate drug most used for the elderly was nifedipine (2.4%). Data from
this study support the relevance of the issue of drug use among the elderly, thus
reinforcing the importance of the evaluation of the process of the prescription
of drugs for this population.
PMID- 25119076
TI - [Vestibular rehabilitation in the quality of life and the symptomatology of
dizziness among the elderly].
AB - The scope of this paper was to analyze the effect of a structured protocol of
vestibular rehabilitation in the symptomatology of dizziness and the quality of
life among the elderly. Nine elderly individuals were attended, namely four males
and five females. The Dizziness Handicap Inventory (DHI) was used to assess
quality of life and the dizziness quantification scale for the symptomatology of
dizziness. A protocol for vestibular rehabilitation consisting of group
activities was then developed. The Wilcoxon test and Student t-test were used for
data analysis. The Spearman correlation coefficient was used to analyze the
relationship between quality of life and the symptomology of dizziness. The
significance level used was 5%. There was significant improvement in the
symptomatology of dizziness, overall quality of life and physical, emotional and
functional aspects after completion of the program. There was also a good
positive correlation between the symptomatology of dizziness and quality of life.
The conclusion reached was that program participants had a significant
improvement of dizziness, general quality of life and their respective vestibular
rehabilitation aspects. There was also a good correlation between symptomatology
of dizziness and overall quality of life.
PMID- 25119077
TI - [Ways of thinking and acting of the elderly when tackling
functionality/disability issues].
AB - Functionality is a crucial dimension of the health of the elderly. The aim of
this work is to investigate the elements that comprise the significance of
disability for the elderly residents of the city of Bambui in the state of Minas
Gerais. A qualitative approach was adopted in which the model of signs,
significance and actions was used in both data collection and analysis.
Interviews were conducted with 57 elderly individuals (30 women; 27 men) ranging
from 61 to 96 years of age registered in primary care units. The participants
interpret functionality/disability (disease) as "being able to cope/not being
able to cope" or "being a burden" (illness) to others. "Not being able to cope"
refers to the inexorable functional loss inherent to the aging process, while
"being a burden" relates to the permanent condition of generating pain and
suffering to both patient and care giver. The way to deal with the "not being
able to cope" condition is related to resignation. On the other hand, praying is
the way to deal with "being a burden." Religion and resignation can help during
critical moments, though they also reveal the lack of resources and alternatives
for support and intervention in the most severe cases.
PMID- 25119078
TI - [Seroepidemiology of Toxoplasma gondii in elderly individuals treated under the
Family Health Strategy, Porto Alegre, Rio Grande do Sul, Brazil].
AB - The aim of this study was to evaluate the seroprevalence of Toxoplasma gondii and
relate it to the socioeconomic, hygienic, sanitary and health conditions of the
elderly of the Family Health Strategy (FHS) in the city of Porto Alegre, Rio
Grande do Sul, Brazil. The research involved a cross-sectional study in which a
questionnaire with epidemiologic questions was applied and blood samples were
taken. The assessment of IgG and IgM anti-T. gondii was performed using the ELISA
technique. Seroprevalence was evaluated among 599 elderly individuals with 88%
for IgG anti-T. gondii and with 0.8% for IgM. In the multivariate analysis, the
variables that associated themselves independently with positive IgG were age
range, personal income and wearing spectacles. Those associated with positive IgM
were age, self-rated health and wearing spectacles. The results call attention to
the high prevalence of IgG anti-T. gondii in elderly individuals in the FHS in
Porto Alegre, generating concern in the event that the reactivation of
toxoplasmosis and the development of more severe symptoms of this infection
occur.
PMID- 25119079
TI - [Cost and characterization of hospital infection among the elderly].
AB - The increase in the number of elderly individuals has a direct impact on the
health system with hospitalization complications such as hospital infection (HI).
The objective of this study is to characterize and evaluate the cost of HI among
the elderly in a public hospital for the elderly. Descriptive, cross-sectional
research was conducted. Elderly individuals with HI in 2010 comprised the
population of the study. The data were drawn from hospital records and analysis
was performed using Excel 2003 and SPSS software. The results indicated that 341
seniors participated in the study with a HI index 3% higher than the monthly
average. The most frequent infectious sites were: respiratory tract infection
(58.1%), urinary tract infection (28.6%) and surgical infection (4.6%). Each
hospitalization cost R$ 28,714.10 on average and 5% of this amount was for
antibiotics. The increase of 15 days average added R$ 17,946.3 to costs of
hospitalization. The conclusion drawn is that the elderly have increased
vulnerability to HI. The infections extend the hospitalization period and
increase costs varying according to the nature of the infection.
PMID- 25119080
TI - [Primary healthcare geared to the needs of the elderly: from theory to practice].
AB - This article seeks to establish a confrontation between theory and practice with
respect to healthcare for the elderly. The theory was evaluated by a study of
documents that comprise the legal and theoretical framework related to the health
of the elderly, which generated a matrix to assess universal access, equity,
comprehensiveness and quality of care. However, the practice of healthcare was
evaluated by a population-based study conducted on 862 elderly individuals and a
census that assessed primary healthcare (PHC) units in two districts of Porto
Alegre in the state of Rio Grande do Sul, Brazil. The variables chosen to verify
the categories were type of care accessed, first contact attribute, wheelchair
accessibility and availability of priority access. Other variables include
comprehensive care and the presence of dental root remains, basic PHC score, the
adequacy of health facilities and ongoing professional training, as well as cross
sectional categories, elderly groups and home care. A mismatch was found between
recommendation and practice in some factors and advances were observed in the
equity and quality of care regarding the ongoing training of professionals.
PMID- 25119081
TI - [Do elderly individuals with a cognitive handicap have worse oral health?].
AB - A comparison of the oral health of elderly people with and without a cognitive
handicap was assessed. The cognitive condition, the indices of decayed, missing,
filled teeth (DMFT), decayed, filled roots (DFR), the need for dental treatment,
the presence of plaque (P), calculus (C), the community periodontal index (CPI),
the rate of periodontal attachment loss (PAL), edentulism, prosthetic use and the
need for prosthetics were evaluated in a complex probabilistic sample by
conglomerates of the elderly (65-74 years). PASW(r) 17.0 was used for the
statistical analyses with correction for the design effect, applying the Mann
Whitney and chi-square test with 95% reliability. A total of 736 elderly
individuals were interviewed and examined. Those with cognitive impairment had
higher average DMFT, DFR and lower average healthy sextant CPI, a lower
prevalence of sextants without plaque/calculus, use of prosthetics and higher
prevalence of edentulism and need for prosthetics. Elderly individuals with a
cognitive handicap had poorer oral health.
PMID- 25119082
TI - [Factors associated with satisfaction with life among elderly caregivers and non
caregivers].
AB - This article seeks to investigate associations between satisfaction with life and
sociodemographic variables, health conditions, functionality, social involvement
and social support among elderly caregivers and non-caregivers, as well as
between satisfaction and the intensity of stress in the caregiver group. A sample
of 338 caregivers was selected according to two items of the Brazilian version of
the Elders Life Stress Inventory. A comparison-group of elderly non-caregivers
was selected at random, with a similar gender, age and income profile. Data were
derived from self-reported questionnaires and scales. Elderly caregivers with low
levels of satisfaction and high levels of stress revealed more symptoms of
insomnia, fatigue, diseases and worse IADL performance. Those with greater
satisfaction and less stress revealed a good level of social support. Insomnia,
depression and fatigue were associated with low satisfaction among caregivers,
and with fatigue, depression and low social support among non-caregivers. It was
considered relevant that instrumental, psychological and informative support can
improve the quality of life and the quality of care provided by elderly
caregivers, especially if they are affected by unfavorable health and
psychosocial conditions and low satisfaction with life.
PMID- 25119083
TI - [Assessment of the technology of care relations in the health services:
perception of the elderly included in the family health strategy in Bambui,
Brazil].
AB - In the health field, technologies of care relations are in the scope of the
worker-user encounter, implying intersubjectivity with the development of
relationships between subjects, resulting in action. Evaluation studies
synthesize knowledge produced on the consequences of using these technologies for
society. This anthropological study aims to understand the perception of the
elderly regarding the resolution capability and effectiveness of the acts
produced in health care relationships in the context of the Family Health
Strategy (ESF). The group studied consisted of 57 elderly residents in Bambui,
State of Minas Gerais, Brazil. The model of signs, meanings and actions was used
for collecting and analyzing data and the semi-structured interview was applied
as a research technique. Elderly individuals assess resolution capability and
effectiveness of the acts of care in the ESF as negative, with relation to the
quality of user and professional interaction. The ESF is not effective and the
desired change in the health care model has not occurred in practice. It repeats
the centrality of the medical-drug-procedure model that treats the disease rather
than the patient, perceiving old age as a disease and illness as being related to
aging.
PMID- 25119084
TI - [Body image perception and associated factors among elderly residents in a city
in northeast Brazil: a population-based study].
AB - The article aims to verify body image perception and associated factors among
elderly individuals in Campina Grande, State of Paraiba. It involves a cross
sectional, population and home-based study, with individuals 60 years or older of
both sexes. Body image perception was considered the dependent variable for
purposes of analysis and study of possible associations. The independent
variables were: age group, nutritional status, number of diseases, health
perception and regular practice of physical activities. To identify associated
factors, univariate and multivariate regression analyses were carried out using
SPSS 17.0 software. Overall, 806 elderly individuals were interviewed. Men showed
greater satisfaction with body image when compared to women and older
participants were more satisfied than younger participants. Among the factors
related to dissatisfaction in women, underweight and overweight/obesity were
associated with an increased risk of dissatisfaction. Among men, older age
constituted a protective factor for dissatisfaction, while underweight and
overweight/obesity were risk factors for dissatisfaction. The results of this
study suggest a possible influence of nutritional status on body image perception
among the elderly, negatively affecting their perception of body image.
PMID- 25119085
TI - [Association between physical and psychosocial impacts of oral disorders and
quality of life among the elderly].
AB - This study sought to evaluate the association between the impact of oral
disorders in terms of physical/psychosocial dimensions and quality of life among
the elderly. It involved a cross-sectional study conducted among the elderly (65
74 years) in 2008/2009. The social impact was assessed using the Oral Health
Impact Profile (OHIP 14) and the quality of life using the SF 12 Short-Form
Health Survey. Descriptive, univariate and multivariate (logistic regression)
analysis was conducted with correction for the design effect, using SPSS(r)18.0
software. Of the 800 individuals approached, 736 elderly individuals participated
(TR = 92%), with a mean age of 67.77 years, the majority of whom showed no impact
based on the measurement of the prevalence of OHIP. The functional limitation
dimension of the OHIP was associated with the physical domain of the SF12,
irrespective of the other variables investigated. However, the seriousness of
OHIP and its psychological discomfort and disability dimensions was associated
with the mental domain of the SF12. The conclusion reached is that some impacts
of oral disorders were associated with unsatisfactory quality of life in the
physical and mental domains.
PMID- 25119086
TI - [Male participation in types of physical activities of a program for the elderly:
a longitudinal study].
AB - The article seeks to describe male participation on a physical activity program
for the elderly in the south of Brazil over a ten-year period (2003-2013). The
data of the study were extracted from a database and assessed using descriptive
and inferential statistics and assessment of the thematic content. The first
phase of the study was longitudinal (from 2003 to 2013) with 163 elderly
participants, while the second phase was cross-sectional for the year of 2013
with 45 elderly individuals. Male participation was, on average, 3.5 times lower
than female participation for all years assessed, and the activity most practiced
was swimming. In the year 2013, the average age of the elderly men was 68 +/- 7.8
years. Most of them are married, have tertiary education, good acquisitive power,
positive self perception of health, one or more diagnosed diseases, and do not
participate in any other physical activity outside the program. According to the
elderly, the reasons for participating most cited was the search for quality of
life and health and, for continuing to exercise, acquiring the taste for the
physical activity. Understanding the profile of these individuals and of the
reasons that motivate them are important tools to comprehend the issue and help
to define public politics directed at this population group.
PMID- 25119087
TI - [Physical inactivity among non-institutionalized elderly individuals: a
population-based study].
AB - The scope of this study is to assess the prevalence of physical inactivity among
the elderly in Northeast Brazil and analyze the associated lifestyle and socio
demographic factors and health conditions. The work presented here is a
descriptive and association-based study using secondary data derived from a
population-based epidemiological study that included 316 elderly participants.
The physical activity level of each participant was assessed using the
International Physical Activity Questionnaire. The explanatory variables examined
in this study were gender, age group, family set-up, ability to read and write,
paid or voluntary employment, smoking, symptoms of depression, high blood
pressure, fasting hyperglycemia and functional capacity. The prevalence of
physical inactivity was 46.5. The results of the multivariate analysis indicated
that physical inactivity was positively associated with the age group >= 80 years
(PR = 2.37), with the lack of an occupation (PR = 4.86) and with dependence on
instrumental activities of daily life (PR = 1.47) and basic activities of daily
life (PR = 1.60). Physical inactivity was highly prevalent in the surveyed
population, making it essential to discuss programs that encourage and enable
increased physical activity to combat the risk factors of a sedentary lifestyle.
PMID- 25119088
TI - [Influence of socioeconomic factors on the quality of life of elderly
hypertensive individuals].
AB - This study sought to evaluate the association between socioeconomic variables and
the quality of life of elderly hypertensive patients treated under the Family
Health Program in the city of Montes Claros, Minas Gerais, Brazil. An analytical
cross study was conducted in a representative sample of 294 elderly hypertensive
patients. Data were collected using a questionnaire on socioeconomic
characteristics and quality of life (MINICHAL). The data were analyzed using the
nonparametric Mann-Whitney and Kuskall-Wallis tests. The results showed that
marital status, religion and education affect the quality of life of elderly
hypertensive patients in a statistically significant way. Elderly hypertensive
patients who were single/divorced/widowed, evangelical, spiritualist and
belonging to other religious bodies, illiterate achieved lower scores in terms of
quality of life. For the remaining variables, there was no statistical
association. The conclusion, drawn is that socioeconomic factors such as marital
status, education and religion influence the quality of life of elderly
hypertensive patients.
PMID- 25119089
TI - [Factors related to the quality of life of the elderly in programs for senior
citizens].
AB - Population aging is a social phenomenon that demands the attention of health
professionals. This article seeks to analyze the influence of possible
intervening factors on the quality of life of the elderly. It was a cross
sectional, quantitative, descriptive and exploratory study, in which 182 elderly
of both genders participated. They were aged >= 60 years and were enrolled in
programs for senior citizens from three universities located in the cities of Sao
Paulo, Sao Caetano do Sul and Mogi das Cruzes. To evaluate the subjective
perception of quality of life, the World Health Organization Quality of Life
questionnaire (WHOQOL-Bref) was used. Multiple linear regression analysis was
performed on the dependent and independent variables. A significance level of 5%
was adopted. The results showed that the absence of disease positively influenced
the quality of life on the four domains evaluated. In the environmental domain,
full tertiary education, old age, the absence of disease and being a resident in
Sao Caetano do Sul positively influenced the quality of life of the elderly. The
factors associated with better quality of life were: full tertiary education, old
age, the absence of disease and being a resident in Sao Caetano do Sul, in that
order of importance.
PMID- 25119090
TI - [Low weight and functional disability in institutionalized elderly interns in
Uberlandia in the State of Minas Gerais, Brazil].
AB - This article seeks to identify the association between nutritional status and
functional dependence in institutionalized elderly interns in Uberlandia, Minas
Gerais. It involved a cross-sectional study with 233 elderly interns in which
sociodemographic variables, nutritional status and degree of dependency were
assessed. Multivariate analysis was performed using Poisson regression with
robust variance to assess the association between nutritional status and
functional dependence of these senior citizens. Low weight by the Body Mass Index
was associated with functional dependence after controlling for socioeconomic and
demographic variables. The elderly with low weight had a prevalence ratio of
dependence of 1.2 times the prevalence rate of dependence of well nourished
elderly interns. As reported in the literature, age was also associated with
dependence with a prevalence ratio of 1.19 for the longest living. Low weight is
an important factor associated with functional disability. Thus, the need for
evaluation, monitoring and recovery of nutritional status in the
institutionalized elderly is stressed, as in addition to reducing morbidity and
mortality from several diseases and improve quality of life, it can also prevent
and delay functional dependency.
PMID- 25119092
TI - [Factors that influence the sexuality of the elderly: an integrative review].
AB - The scope of this article is to analyze the scientific evidence addressing the
factors that influence the sexuality of the elderly. It involved an online search
carried out in pairs, including original articles published between 2006 and
October 2011 in Portuguese, English or Spanish, which fulfilled the requirements
of the study. The MEDLINE, LILACS, CidSaude and BDENF databases were used with
the key words: sexualidade e idoso / sexuality and elderly / sexualidad y
anciano. The articles selected were assessed for methodological quality using two
instruments, namely CASP and the Hierarchical Classification of Evidence. After
analysis, 15 articles were included in the review, which discuss the culture of
asexuality of the elderly, whereby the experience of sexuality only prevails
among younger people. The absence of the partner due to widowhood, attributing
value to beauty standards of the young, the occurrence of disease, use of
medication, and changes in sexual physiology were identified as important factors
that influence the sexuality of the elderly. The conclusion drawn is that social
and cultural factors, changes in body physiology, and the occurrence of disease
interfere with the sexuality of the elderly, making it necessary for nursing
professionals to be proactive in debunking myths and providing orientation.
PMID- 25119091
TI - [Evaluation of the quality of primary health care from the perspective of the
elderly].
AB - The scope of this study was to assess the quality of Primary Health Care (PHC)
provided to the elderly from their viewpoint. The study design was cross
sectional and observational in a stratified random sample of elderly individuals,
enrolled in 10 of the 20 Basic Health Units (BHU) in the city of Macaiba, State
of Rio Grande do Norte, Brazil. After an interview conducted using the adult
version of the primary care assessment tool (PCATool-Brazil), the quality level
was estimated (0-10, based on desirable attributes) and the association between
demographic and socioeconomic factors was analyzed. The participants (n = 100)
assigned a score of fair (5.7) to Quality; Longitudinality of care was awarded a
high score (7.3), however Integrality (4.7), Family Orientation (4.1) and
Accessibility (3.8) were considered weak. Socio-demographic factors linked to
vulnerability (low income, rural area and older age) were positively associated
with different PHC attributes. A margin for improvement in PHC attributes was
observed, especially with respect to increasing the focus on the family,
extending working hours in BHUs and enhancing prevention of diseases and ensuing
complications.
PMID- 25119093
TI - [Factors associated with the danger of accidental falls among institutionalized
elderly individuals: an integrative review].
AB - The scope of this research is to identify the major risk factors associated with
accidental falls among the elderly. It involves an integrative review of the
literature between 2002 and 2012 in English and Portuguese. The selection of
articles was based on the following key words in the Lilacs, Medline and BDENF
databases: accidental falls, homes for the elderly and health services. In the
final sample 19 articles were selected, of which 11 were national and 8 were
international. They indicate that the major factors related to the risk of
accidental falls in Homes for the Elderly are: being female, being diagnosed with
chronic disease, treatment with benzodiazepine, earlier cases of accident falls,
and mobility restriction. The research reveals that architectonic and furniture
inadequacies in Homes for the Elderly may be predisposing factors for accidental
falls. Analysis of the articles reveals the need for further longitudinal studies
and, consequently, enhanced monitoring of the conditions of the functional
capacity of the elderly, especially the risks related to falls, considered one of
the leading causes of death among institutionalized elderly individuals.
PMID- 25119094
TI - [Health promotion in primary care: study based on the Paulo Freire method].
AB - The scope of this study is to analyze the implementation of health promotion
actions in the working process of the Family Health Teams of a city in the state
of Santa Catarina. It involves research adopting a qualitative approach linked to
the methodological benchmark of Paulo Freire, consisting of three dialectic
moments: thematic investigation; encoding and decoding; critical revelation.
Fifteen Culture Circles were conducted, covering five district health units, with
the participation of 70 professionals. Each meeting was scheduled to last two
hours with an average attendance of thirteen participants of the Family Health
teams. The research revealed that there are limitations to the implementation of
health promotion as a key element of participatory action together with the
community. It also highlighted the importance of interdisciplinarity and
intersectorality between workers and the city, state and federal manager. The
commitment to the principles of the Unified Health System (SUS) and health
promotion also presents itself as a challenge to improve the quality of life of
the population.
PMID- 25119095
TI - [The Singular Therapeutic Project and mental health practices at Family Health
Support Centers in Guarulhos in the state of Sao Paulo, Brazil].
AB - Various studies describe the Singular Therapeutic Project (STP) as a powerful
instrument of care for the users of specialized mental health services. It is
also put forward as a tool to organize and support the activities of the Family
Health Support Centers (FHSC), based on the concepts of co-responsibility and
comprehensive care. The article seeks to analyze the development of STP by mental
health teams of FHSC and its articulations with services of Primary Health Care
(PHC), psychosocial services and other sectors of society. It involved
qualitative research performed in Guarulhos in the state of Sao Paulo in 2012 by
systematic observation and conducting semi-structured interviews with mental
health professionals from support centers. The content analysis method was
employed for interpretation of the findings. The STP in FHSC faces obstacles
related to lack of definition of work object (attention or management?),
precarious working conditions and overlapping functions. It is necessary to
analyze the technological feasibility of the STP based on the peculiarities of
PHC, avoiding straightforward transposition of technological tools among the
different services that comprise the psychosocial care network.
PMID- 25119096
TI - [Cross-cultural adaptation and validation of the Health and Taste Attitude Scale
(HTAS) in Portuguese].
AB - The scope of this study was to show the cross-cultural adaptation and validation
of the Health and Taste Attitude Scale in Portuguese. The methodology included
translation of the scale; evaluation of conceptual, operational and item-based
equivalence by 14 experts and 51 female undergraduates; semantic equivalence and
measurement assessment by 12 bilingual women by the paired t-test, the Pearson
correlation coefficient and the coefficient intraclass correlation; internal
consistency and test-retest reliability by Cronbach's alpha and intraclass
correlation coefficient, respectively, after application on 216 female
undergraduates; assessment of discriminant and concurrent validity via the t-test
and Spearman's correlation coefficient, respectively, in addition to Confirmatory
Factor and Exploratory Factor Analysis. The scale was considered adequate and
easily understood by the experts and university students and presented good
internal consistency and reliability (u 0.86, ICC 0.84). The results show that
the scale is valid and can be used in studies with women to better understand
attitudes related to taste.
PMID- 25119097
TI - [Meat consumption by adults in southern Brazil: a population-based study].
AB - This paper is the result of a cross-sectional population-based study that
evaluated individuals aged 20 or more living in the urban area of Pelotas in the
state of Rio Grande do Sul and sought to describe the frequency of meat
consumption and the habit of eating meat with an excess of fat. It evaluated the
consumption over the past year of red meat (including bone, steak and ground
beef), white meats (chicken and fish) and viscera and processed meats. Of the
2,730 people interviewed, 99.1% (CI95% 98.7 - 99.5) consumed some type of meat
over the past year, while around 32% reported daily consumption. The prevalence
of consumption of red meat (99.3% CI95% 98.9 - 99.6) and white meat (99.4% CI95%
99.1 - 99.7) was similar. Chicken was the meat most consumed by interviewees
(98.0% CI95% 97.4 - 98.5), while viscera were the least consumed (59.1% CI95%
56.4 - 61.7). The processed meats consumed by 85.5% (CI95% 83.7 - 87.2) of the
respondents, presented the highest prevalence of daily consumption (16.6%). Meats
with excess of fat were consumed by 52.3% (CI95% 49.8 - 54.8) of adults,
especially men and people of lower education and economic status.
PMID- 25119098
TI - [Contractual arrangements in primary health care: the experience of Portugal and
Brazil].
AB - The contractual arrangements adopted in the Family Health Strategy are a topic as
yet scantly addressed in studies. It is introduced in Brazil in different models
in accordance with the contracting entity and the legal status of the contracted
service provider; and in Portugal, it is based on a model of inter-governmental
contractual arrangements with the Family Health Units. In this paper, the current
status of contractual arrangements in both countries is presented and their
attributes of joint planning, accountability with autonomy and performance-based
incentive programs are discussed. The main contributions are: better coordination
of the health organizations; substitution of the hierarchical command-control
logic with greater participation; and accountability of professionals with
enhanced performance of their activities. The conclusion reached is that one of
the facilitating elements is gradual construction, in an environment of ongoing
learning, with health professionals playing the leading role. However, the major
challenges include transparency in the implementation of processes, the
enforcement of sound auditing mechanisms and information systems, as well as the
continuous review of indicators and their suitability for the health needs of the
population.
PMID- 25119099
TI - [Alteration of profile of treatment of the public psychiatric hospitals of Belo
Horizonte, Brazil, in the context of mental health care reform].
AB - This article seeks to describe the profile of treatment and internment in public
psychiatric hospitals in Belo Horizonte, Brazil, from 2002 to 2011. The changes
in the characteristics of treatment and the profiles of the patients treated are
analyzed in the context of health care reform. It is a study of temporal series
with trend analysis by means of linear regression. There was a reduction in the
total of patients treated in the period under scrutiny. Inversely, there was an
increase in internments with a reduction in length of stay, though no change in
readmission rates. Patients from Belo Horizonte prevailed, however a relative
increase in demand from the surrounding area was observed. There was a reversal
in the prevalence of morbidity switching from psychotic disorders to disorders
resulting from the use of alcohol and/or other drugs. The alteration observed in
the profile of treatment in public psychiatric hospitals in Belo Horizonte was
concomitant with the progressive implementation of community mental health
services, which have probably met the demand that was formerly directed to these
hospitals. Currently the psychiatric hospital is not the first, much less the
only venue for treatment in the mental health network in Minas Gerais.
PMID- 25119102
TI - Anti-inflammatory activity of methanol extract and n-hexane fraction
mojabanchromanol b from Myagropsis myagroides.
AB - AIMS: This study was carried out to verify the anti-inflammatory effect of
methanol extract from Myagropsis myagroides (MMME) and its n-hexane fraction
mojabanchromanol b. MAIN METHODS: The murine macrophages Raw264.7 cells were
used. The pro-inflammatory cytokines (IL-6, IL-1beta, TNF-alpha) and the
expression of iNOS, COX-2, and NF-kappaB p65 were examined by ELISA and
immunoblotting. To investigate the inhibitory effect of MMME in an animal model
of inflammation, an assay to determine croton oil-induced ear edema in mice was
performed. KEY FINDINGS: NO levels decreased with increasing concentration of
MMME, and were inhibited up to 50%. The secretion of IL-6, TNF-alpha, and IL
1beta was suppressed in a dose-dependent manner, especially at 50MUg/mL,
inhibition activities of cytokines were over 50%. MMME also suppressed the
expression of COX-2, iNOS, and NF-kappaB p65, suggesting that MMME could affect
the expression of inflammation related cytokines and proteins through the
deregulation of NF-kappaB. Moreover, the formation of mouse ear edema was reduced
at the highest dose tested compared to that in the control, and generated similar
effects compared with prednisolone at 250mg/kg in mice ear edema evaluation test.
In addition, the results in photomicrograph of mice ear tissue and mast cells
also showed the same effect. After purification of fractions of MMME, it
indicated that n-hexane fraction mojabanchromanol b was the most active fraction
showing the inhibitory effect of IL-6 and TNF-alpha. SIGNIFICANCE: These results
suggested that MMME and mojabanchromanol b may have great effects on inflammatory
factors and be potential anti-inflammatory therapeutic materials.
PMID- 25119103
TI - The effects of PTBP3 silencing on the proliferation and differentiation of MKN45
human gastric cancer cells.
AB - AIMS: PTBP3 overexpression inhibits the differentiation of leukemia cells;
however, its effects on the differentiation and proliferation of solid cancer
cells remain unclear. Thus, the impact of PTBP3 on the differentiation and
proliferation of gastric cancer cells was investigated. MAIN METHODS: PTBP3
expression was analyzed in normal and tumor tissues using immunohistochemistry. A
xenograft model was established in nude mice by subcutaneous injection of
untransfected human gastric cancer MKN45 cells or those expressing a control
vector or PTBP3 siRNA. We analyzed the tumor inhibition rate, the expression of
PTBP3, the PCNA-positive rate and the serum levels of CEA, CA199, CA125, LDH, ALP
and gamma-GT in different groups. KEY FINDINGS: The tumor weights in the PTBP3
siRNA group were significantly lower than that of the MKN45 cell control group
(P<0.001). Immunohistochemistry analysis of PCNA expression revealed that it was
markedly reduced after PTBP3 silencing. ELISAs showed that the serum levels of
CEA and CA199 tumor markers as well as LDH and ALP were reduced after PTBP3
silencing. Transmission electron microscopy revealed that MKN45 cells expressing
PTBP3 siRNA had reduced nuclear-to-cytoplasmic ratio and regular nuclei,
suggesting differentiation. SIGNIFICANCE: PTBP3 may promote proliferation and
inhibit the differentiation of human gastric cancer MKN45 cells.
PMID- 25119104
TI - Preparation, characterisation and bioactivity evaluation of the inclusion complex
formed between picoplatin and gamma-cyclodextrin.
AB - The inclusion complex of picoplatin with gamma-cyclodextrin (gamma-CD) was
prepared and characterised by different analytical methods, including NMR, FTIR,
TGA, phase solubility as well as SEM. All of these approaches indicated that
picoplatin was able to form an inclusion complex with gamma-CD, and that the
picoplatin/gamma-CD inclusion compounds exhibited different spectroscopic
features and properties from free picoplatin. The stoichiometry of the complex
was 1:1; the pyridine group of picoplatin was deeply inserted into the cavity of
gamma-CD and the amine platinum group of picoplatin was near the narrower rim of
gamma-CD. The calculated apparent stability constant of the complex was 10,318M(
1). Moreover, the water solubility of picoplatin was significantly improved,
according to phase-solubility studies. The complex maintained its anticancer
activity, as shown by an in vitro cell-survival assay on A549 and MCF-7 cancer
cell lines. All of these results showed that inclusion complexation may be a
promising strategy to design a novel formulation of picoplatin as an anticancer
therapy.
PMID- 25119105
TI - In vitro induced regulatory T cells are unique from endogenous regulatory T cells
and effective at suppressing late stages of ongoing autoimmunity.
AB - Strategies to boost the numbers and functions of regulatory T cells (Tregs) are
currently being tested as means to treat autoimmunity. While Tregs have been
shown to be effective in this role, strategies to manipulate Tregs to effectively
suppress later stages of ongoing diseases need to be established. In this study,
we evaluated the ability of TGF-beta-induced Tregs (iTregs) specific for the
major self-antigen in autoimmune gastritis to suppress established autoimmune
gastritis in mice. When transferred into mice during later stages of disease,
iTregs demethylated the Foxp3 promoter, maintained Foxp3 expression, and
suppressed effector T cell proliferation. More importantly, these iTregs were
effective at stopping disease progression. Untreated mice had high numbers of
endogenous Tregs (enTregs) but these were unable to stop disease progression. In
contrast, iTregs, were found in relatively low numbers in treated mice, yet were
effective at stopping disease progression, suggesting qualitative differences in
suppressor functions. We identified several inhibitory receptors (LAG-3, PD-1,
GARP, and TNFR2), cytokines (TGF-beta1 and IL12p35), and transcription factors
(IRF4 and Tbet) expressed at higher levels by iTregs compared to enTregs isolated
form mice with ongoing disease, which likely accounts for superior suppressor
ability in this disease model. These data support efforts to use iTregs in
therapies to treat establish autoimmunity, and show that iTregs are more
effective than enTregs at suppressing inflammation in this disease model.
PMID- 25119110
TI - Topological insulator states in a honeycomb lattice of s-triazines.
AB - Two-dimensional (2D) graphitic carbon nitride materials have been drawing
increasing attentions in energy conversion, environment protection and spintronic
devices. Here, based on first-principles calculations, we demonstrate that the
already-synthesized honeycomb lattice of s-triazines with a chemical formula of
C6N6 (g-C6N6) has topologically nontrivial electronic states characterized by
px,y-orbital band structures with a topological invariant of Z2 = 1, and stronger
spin-orbital coupling (SOC) than both graphene and silicene. The band gaps opened
in the px,y-orbital bands due to SOC are 5.50 meV (K points) and 8.27 eV (Gamma
point), respectively, implying that the quantum spin Hall effect (QSHE) could be
achieved in this 2D graphitic carbon nitride material at a temperature lower than
95 K. This offers a viable approach for searching for 2D Topological Insulators
(TIs) in metal-free organic materials.
PMID- 25119106
TI - The DNA binding property of PML/RARA but not the integrity of PML nuclear bodies
is indispensable for leukemic transformation.
AB - PML/RARA is the oncoprotein driving acute promyelocytic leukemia (APL). It
suppresses genes expression by recruitment of a number of transcriptional
repressors, resulting in differentiation block and malignant transformation of
hematopoietic cells. Here, we found that mice primary hematopoietic progenitor
cells (HPCs), transduced by DNA-binding-defective PML/RARA mutants, were
deficient in colony formation. Further experiments showed that DNA-binding
defective PML/RARA mutants could not repress the transcription of retinoic acid
regulated genes. Intriguingly, there were no significant differences of the micro
speckled intracellular distribution between the mutants and wild-type PML/RARA.
Some retinoic acid target genes regulated by PML/RARA are involved in not only
differentiation block but also hematopoietic cell self-renewal. Altogether, our
data demonstrate that direct DNA-binding is essential for PML/RARA to immortalize
hematopoietic cells, while disruption of PML-nuclear body does not seem to be a
prerequisite for hematopoietic cell transformation.
PMID- 25119111
TI - Integrating metalloporphycenes into p-type NiO-based dye-sensitized solar cells.
AB - In the current work, we have explored a novel synthetic route towards metalated
porphycenes and their use in p-type NiO-based dye-sensitized solar cells.
Particular emphasis is placed on the influence that the relative positioning of
the anchoring group exerts on the DSSC performance.
PMID- 25119112
TI - Ionic-liquid-micelle-functionalized mesoporous Fe3O4 microspheres for
ultraperformance liquid chromatography determination of anthraquinones in dietary
supplements.
AB - A magnetic solid-phase extraction method using ionic liquid (IL)-micelle
functionalized mesoporous Fe3O4 microspheres (MFMs) was proposed for the
preconcentration of anthraquinones in dietary supplements. The analytes were then
determined by ultraperformance liquid chromatography combined with an ultraviolet
detector. The extraction parameters, such as the choice of ILs, the
concentrations of ILs and MFMs, the pH of diluent, and the concentration of
acetic acid in the eluent, were presented. Under the optimized conditions, the
limits of detection and limits of quantitation were 0.4-2.8 ng mL(-1) and 1.4-9.4
ng mL(-1), respectively. The accuracy of the proposed method was investigated by
recovery in herb and granules of Radix et Rhizoma Rhei, yielding values between
89.25% and 96.48%. The use of the proposed method in the sample pretreatment of
complex dietary supplements is feasible due to the high surface area and
excellent adsorption capacity of MFMs after modification with IL.
PMID- 25119107
TI - Risk factors and adverse perinatal outcomes among term and preterm infants born
small-for-gestational-age: secondary analyses of the WHO Multi-Country Survey on
Maternal and Newborn Health.
AB - BACKGROUND: Small for gestational age (SGA) is not only a major indicator of
perinatal mortality and morbidity, but also the morbidity risks in later in life.
We aim to estimate the association between the birth of SGA infants and the risk
factors and adverse perinatal outcomes among twenty-nine countries in Africa,
Latin America, the Middle East and Asia in 359 health facilities in 2010-11.
METHODS: We analysed facility-based, cross-sectional data from the WHO Multi
country Survey on Maternal and Newborn Health. We constructed multilevel logistic
regression models with random effects for facilities and countries to estimate
the risk factors for SGA infants using country-specific birthweight reference
standards in preterm and term delivery, and SGA's association with adverse
perinatal outcomes. We compared the risks and adverse perinatal outcomes with
appropriate for gestational age (AGA) infants categorized by preterm and term
delivery. RESULTS: A total of 295,829 singleton infants delivered were analysed.
The overall prevalence of SGA was highest in Cambodia (18.8%), Nepal (17.9%), the
Occupied Palestinian Territory (16.1%), and Japan (16.0%), while the lowest was
observed in Afghanistan (4.8%), Uganda (6.6%) and Thailand (9.7%). The risk of
preterm SGA infants was significantly higher among nulliparous mothers and
mothers with chronic hypertension and preeclampsia/eclampsia (aOR: 2.89; 95% CI:
2.55-3.28) compared with AGA infants. Higher risks of term SGA were observed
among sociodemographic factors and women with preeclampsia/eclampsia, anaemia and
other medical conditions. Multiparity (> = 3) (AOR: 0.88; 95% CI: 0.83-0.92) was
a protective factor for term SGA. The risk of perinatal mortality was
significantly higher in preterm SGA deliveries in low to high HDI countries.
CONCLUSION: Preterm SGA is associated with medical conditions related to
preeclampsia, but not with sociodemographic status. Term SGA is associated with
sociodemographic status and various medical conditions.
PMID- 25119114
TI - Syntheses and structures of copper complexes of 3-(6-(1H-pyrazol-1-yl)pyridin-2
yl)pyrazol-1-ide and their excellent performance in the syntheses of nitriles and
aldehydes.
AB - Reactions of a pincer ligand 2-(1H-pyrazol-1-yl)-6-(1H-pyrazol-3-yl)pyridine
(pzpypzH) with Cu(NO3)2, Cu(ClO4)2, CuSO4, CuCl2 or CuI produced three dinuclear
Cu(ii) complexes [{Cu(NO3)}(MU-pzpypz)]2 (1), [{Cu(ClO4)}(MU-pzpypz)]2 (2),
[Cu2(MU-SO4)(MU-pzpypz)2].2MeOH (3.2MeOH), one mononuclear Cu(ii) complex
[CuCl2(pzpypzH)] (4) and one trinuclear Cu(i)/Cu(ii) complex [(ICu)(MU-I)2Cu2(MU
pzpypz)2] (5), respectively. Treatment of 4 with two equiv. of AgNO3 in DMF also
gave rise to 1. Complexes 1-5 were characterized by elemental analysis, IR
spectroscopy and single-crystal X-ray diffraction. Complex 1 or 2 has a dimeric
structure in which two {Cu(X)} (X = NO3, ClO4) fragments are interconnected by
two MU-pzpypz(-) ligands. 3 also adopts a dimeric structure in which two Cu(ii)
centers are interconnected by a pair of MU-pzpypz(-) ligands and one MU-SO4(2-)
ion. The Cu(ii) center in 4 is five-coordinated by three N atoms of the pzpypzH
ligand and two Cl atoms. In 5, two Cu(ii) centers are bridged by two MU-pzpypz(-)
ligands and one CuI3(2-) unit, forming a unique trinuclear structure. Complexes 1
5 displayed high catalytic activity toward the ammoxidation of alcohols to
nitriles and the aerobic oxidation of alcohols to aldehydes in H2O. The nitrile
or aldehyde products could be readily separated from the catalytic system by
extraction and the residual aqueous solution containing 1 retained good activity
for several cycles.
PMID- 25119115
TI - Electrochemical behavior of the 1,10-phenanthroline ligand on a multiwalled
carbon nanotube surface and its relevant electrochemistry for selective
recognition of copper ion and hydrogen peroxide sensing.
AB - 1,10-Phenanthroline (Phen) is a well-known benchmark ligand and has often been
used in the coordination chemistry for the complexation of transition metal ions,
such as Fe(2+), Ni(2+), and Co(2+). Because the electro-oxidation potential of
Phen is much higher (>2 V versus Ag/AgCl) than the water decomposition potential,
i.e., ~1.5 V versus Ag/AgCl, in pH 7, it is practically difficult to electro
oxidize Phen in aqueous medium using any conventional electrodes, such as glassy
carbon electrode (GCE), gold, and platinum. Interestingly, herein, we report an
unexpected oxidation of Phen to a highly redox active 1,10-phenanthroline-5,6
dione (Phen-dione) and its confinement on a multiwalled carbon nanotube (MWCNT)
modified glassy carbon electrode (GCE/MWCNT@Phen-dione) surface by potential
cycling of Phen-adsorbed GCE/MWCNT (GCE/MWCNT@Phen) from -1 to 1 V versus Ag/AgCl
in pH 7 phosphate buffer solution. GCE/MWCNT@Phen-dione showed selective
recognition of copper ion (GCE/MWCNT@Phen-dione-Cu(2+)) by catalyzing the
hydrogen peroxide reduction reaction in a neutral pH solution. The precise
structure of the Phen electro-oxidized product has been identified after
characterizing the electrode and/or ethanolic extract of the product by various
techniques, such as Raman, Fourier transform infrared spectroscopy (FTIR), X-ray
photoelectron spectroscopy (XPS) (for copper complex), liquid chromatography-mass
spectrometry (LC-MS), electrospray ionization-mass spectrometry (ESI-MS) (for
copper complex), cyclic voltammetry (CV), and in situ electrochemical quartz
crystal microbalance (EQCM) and comparing electrochemical behavior of several
control compounds, such as phenanthrene and 9,10-phenanthrenequinone. It is
concluded that the product formed is 1,10-phenanthroline-5,6-dione, wherein the
dione position is ortho to each other and the copper ion is complexed with
nitrogen of the phenanthroline ring. With extended electrochemical oxidation of a
structurally similar ligand, 2,2'-bipyridine failed to show any such
electrochemical dynamics. Finally, applicability of GCE/MWCNT@Phen-dione-Cu(2+)
for electrochemical sensing of hydrogen peroxide in a couple of real samples is
successfully demonstrated.
PMID- 25119113
TI - Identification and association of the single nucleotide polymorphisms, C-509T,
C+466T and T+869C, of the TGF-beta1 gene in patients with asthma and their
influence on the mRNA expression level of TGF-beta1.
AB - Transforming growth factor-beta1 (TGF-beta1) is an important fibrogenic and
immunomodulatory cytokine participating in the pathogenesis of a number of
illnesses related to the growth, differentiation and migration of cells. It also
plays a key role in inflammation, atherosclerosis, vascular inflammation and
asthma. The aim of the present study was to evaluate the association between the
expression of the TGF-beta1 gene and its genetic polymorphisms, and the disease
phenotype. The study comprised 173 patients with asthma, as well as 163 healthy
volunteers as a control group. The gender profiles of the groups were similar
(p=0.8415). Genotyping was performed by polymerase chain reaction (PCR)-high
resolution melting (HRM). The results were verified by sequencing. Gene
expression was evaluated by RT-PCR. This study evaluated the role and frequency
of genetic polymorphisms (C-509T, C+466T and T+869C) of the TGF-beta1 gene in the
study group (patients with asthma) and the control group (healthy volunteers).
The results obtained for the patients and healthy controls were as follows: C
509T single nucleotide polymorphism (SNP) (controls, TT/CT/CC
0.4444/0.5309/0.0247; patients, TT/CT/CC-0.3699/0.6012/0.0289), C+466T SNP
(controls, TT/CT/CC-1.000/0.000/0.000; patients, TT/CT/CC-1.000/0.000/0.000) and
T+869C SNP (controls, TT/CT/CC-1.000/0.000/0.000; patients, TT/CT/CC
1.000/0.000/0.000). Only the C-509T polymorphism was found to play a significant
role in the pathogenesis of asthma, as well as a risk factor in the loss of the
clinical control of the disease [TT vs. CC/CT, odds ratio (OR) 2.38; confidence
interval (CI) 1.22-4.66; p=0.0103]. A significant difference was noted between
the study and control groups with regard to the mRNA expression of TGF-beta1
(p=0.0133). A higher level of expression of the TGF-beta1 gene correlated with
the time of diagnosis of patients over 16 years of age (p=0.0255). This study
demonstrates that the C-509T SNP is a significant clinical risk factor for asthma
and that the TGF-beta1 cytokine contributes to the progression of the illness.
PMID- 25119116
TI - Comparison of two non-mydriatic fundus cameras to obtain retinal arterio-venous
ratio.
AB - PURPOSE: To analyze device-dependent variability of two non-mydriatic fundus
cameras to obtain arterio-venous ratio (AVR), central retinal arteriolar
equivalent (CRAE), and central retinal venular equivalent (CRVE) in static vessel
analysis (SVA). METHODS: We examined 53 participants (29 men, 24 women; median
age 46 years) of the Study of Health in Pomerania (SHIP). We took 45 degrees
optic-disc-centered fundus images of the right eye with two different non
mydriatic fundus cameras. The first photograph was obtained from the TRC-NW 200,
the second from the OCT 2000 (both Topcon Corporation, Tokyo, Japan). One
experienced grader graded image quality from 1 "ideal quality" to 5 "not
analyzable" and determined AVR, CRAE, and CRVE with the software Vesselmap3
(Imedos, Jena, Germany). RESULTS: Average image quality was 1.8 for the TRC-NW
200 and 1.6 for the OCT 2000. AVR could not be determined in 5 images of the TRC
NW 200 due to low image quality, while six images of the OCT 2000 were not
analyzable. The difference between AVR taken from two different non-mydriatic
cameras was 0.01 +/- 0.03 in Bland-Altman plots. The difference between CRAE was
0.17 +/- 10.15 and between CRVE was -2.32 +/- 11.76. CONCLUSIONS: The two
different non-mydriatic cameras showed good agreement with respect to image
quality. When using the same reading software, AVR, CRAE, and CRVE agreed well.
Thus, funduscopy and SVA seem to be robust against inter-device variability. As a
result, device dependency can remain unconsidered in follow-up examinations with
different technical equipment. However, variability might impact more with
devices from different manufacturers.
PMID- 25119117
TI - Randomized clinical trial on epidural versus patient-controlled analgesia for
laparoscopic colorectal surgery within an enhanced recovery pathway.
AB - OBJECTIVE: To compare epidural analgesia (EDA) to patient-controlled opioid-based
analgesia (PCA) in patients undergoing laparoscopic colorectal surgery.
BACKGROUND: EDA is mainstay of multimodal pain management within enhanced
recovery pathways [enhanced recovery after surgery (ERAS)]. For laparoscopic
colorectal resections, the benefit of epidurals remains debated. Some consider
EDA as useful, whereas others perceive epidurals as unnecessary or even
deleterious. METHODS: A total of 128 patients undergoing elective laparoscopic
colorectal resections were enrolled in a randomized clinical trial comparing EDA
versus PCA. Primary end point was medical recovery. Overall complications,
hospital stay, perioperative vasopressor requirements, and postoperative pain
scores were secondary outcome measures. Analysis was performed according to the
intention-to-treat principle. RESULTS: Final analysis included 65 EDA patients
and 57 PCA patients. Both groups were similar regarding baseline characteristics.
Medical recovery required a median of 5 days (interquartile range [IQR], 3-7.5
days) in EDA patients and 4 days (IQR, 3-6 days) in the PCA group (P = 0.082).
PCA patients had significantly less overall complications [19 (33%) vs 35 (54%);
P = 0.029] but a similar hospital stay [5 days (IQR, 4-8 days) vs 7 days (IQR,
4.5-12 days); P = 0.434]. Significantly more EDA patients needed vasopressor
treatment perioperatively (90% vs 74%, P = 0.018), the day of surgery (27% vs 4%,
P < 0.001), and on postoperative day 1 (29% vs 4%, P < 0.001), whereas no
difference in postoperative pain scores was noted. CONCLUSIONS: Epidurals seem to
slow down recovery after laparoscopic colorectal resections without adding
obvious benefits. EDA can therefore not be recommended as part of ERAS pathways
in laparoscopic colorectal surgery.
PMID- 25119118
TI - Assessing Technical Competence in Surgical Trainees: A Systematic Review.
AB - OBJECTIVE: To systematically examine the literature describing the methods by
which technical competence is assessed in surgical trainees. BACKGROUND: The last
decade has witnessed an evolution away from time-based surgical education. In
response, governing bodies worldwide have implemented competency-based education
paradigms. The definition of competence, however, remains elusive, and the impact
of these education initiatives in terms of assessment methods remains unclear.
METHODS: A systematic review examining the methods by which technical competence
is assessed was conducted by searching MEDLINE, EMBASE, PsychINFO, and the
Cochrane database of systematic reviews. Abstracts of retrieved studies were
reviewed and those meeting inclusion criteria were selected for full review. Data
were retrieved in a systematic manner, the validity and reliability of the
assessment methods was evaluated, and quality was assessed using the Grading of
Recommendations Assessment, Development and Evaluation classification. RESULTS:
Of the 6814 studies identified, 85 studies involving 2369 surgical residents were
included in this review. The methods used to assess technical competence were
categorized into 5 groups; Likert scales (37), benchmarks (31), binary outcomes
(11), novel tools (4), and surrogate outcomes (2). Their validity and reliability
were mostly previously established. The overall Grading of Recommendations
Assessment, Development and Evaluation for randomized controlled trials was high
and low for the observational studies. CONCLUSIONS: The definition of technical
competence continues to be debated within the medical literature. The methods
used to evaluate technical competence predominantly include instruments that were
originally created to assess technical skill. Very few studies identify standard
setting approaches that differentiate competent versus noncompetent performers;
subsequently, this has been identified as an area with great research potential.
PMID- 25119119
TI - Glycopeptides versus beta-lactams for the prevention of surgical site infections
in cardiovascular and orthopedic surgery: a meta-analysis.
AB - OBJECTIVE: To compare the efficacy of glycopeptides and beta-lactams in
preventing surgical site infections (SSIs) in cardiac, vascular, and orthopedic
surgery. BACKGROUND: The cost-effectiveness of switching from beta-lactams to
glycopeptides for preoperative antibiotic prophylaxis has been controversial.
beta-Lactams are generally recommended in clean surgical procedures, but they are
ineffective against resistant gram-positive bacteria. METHODS: PubMed,
International Pharmaceuticals Abstracts, Scopus, and Cochrane were searched for
randomized clinical trials comparing glycopeptides and beta-lactams for
prophylaxis in adults undergoing cardiac, vascular, or orthopedic surgery.
Abstracts and conference proceedings were included. Two independent reviewers
performed study selection, data extraction, and assessment of risk of bias.
RESULTS: Fourteen studies with a total of 8952 patients were analyzed. No
difference was detected in overall SSIs between antibiotic types. However,
compared with beta-lactams, glycopeptides reduced the risk of resistant
staphylococcal SSIs by 48% (relative risk, 0.52; 95% confidence interval, 0.29
0.93; P = 0.03) and enterococcal SSIs by 64% (relative risk, 0.36; 95% confidence
interval, 0.16-0.80; P = 0.01), but increased respiratory tract infections by 54%
(relative risk, 1.54; 95% confidence interval, 1.19-2.01; P <= 0.01). Subgroup
analysis of cardiac procedures showed superiority of beta-lactams in preventing
superficial and deep chest SSIs, susceptible staphylococcal SSIs, and respiratory
tract infections. CONCLUSIONS: Glycopeptides reduce the risk of resistant
staphylococcal SSIs and enterococcal SSIs, but increase the risk of respiratory
tract infections. Additional high-quality randomized clinical trials are needed
as these results are limited by high risk of bias.
PMID- 25119120
TI - Laparoscopic repair of very large hiatus hernia with sutures versus absorbable
mesh versus nonabsorbable mesh: a randomized controlled trial.
AB - OBJECTIVE: Determine whether absorbable or nonabsorbable mesh in repair of large
hiatus hernias reduces the risk of recurrence, compared with suture repair.
BACKGROUND: Repair of large hiatus hernia is associated with radiological
recurrence rates of up to 30%, and to improve outcomes mesh repair has been
recommended. Previous trials have shown less short-term recurrence with mesh, but
adverse outcomes limit mesh use. METHODS: Multicentre prospective double blind
randomized controlled trial of 3 methods of repair: sutures versus absorbable
mesh versus nonabsorbable mesh. Primary outcome-hernia recurrence assessed by
barium meal radiology and endoscopy at 6 months. Secondary outcomes-clinical
symptom scores at 1, 3, 6, and 12 months. RESULTS: A total of 126 patients
enrolled: 43 sutures, 41 absorbable mesh, and 42 nonabsorbable mesh. Among them,
96.0% were followed up to 12 months, with objective follow-up data in 92.9%. A
recurrent hernia (any size) was identified in 23.1% after suture repair, 30.8%
after absorbable mesh, and 12.8% after nonabsorbable mesh (P = 0.161). Clinical
outcomes were similar, except less heartburn at 3 and 6 months and less bloating
at 12 months with nonabsorbable mesh; more heartburn at 3 months, odynophagia at
1 month, nausea at 3 and 12 months, wheezing at 6 months; and inability to belch
at 12 months after absorbable mesh. The magnitudes of the clinical differences
were small. CONCLUSIONS: No significant differences were seen for recurrent
hiatus hernia, and the clinical differences were unlikely to be clinically
significant. Overall outcomes after sutured repair were similar to mesh repair.
PMID- 25119121
TI - Indeterminate Pulmonary Nodules in Colorectal Cancer: Follow-up Guidelines Based
on a Risk Predictive Model.
AB - BACKGROUND: Chest computed tomographic (CT) scans frequently detect indeterminate
pulmonary nodules (IPNs) in patients with colorectal cancer. The discovery of
such nodules creates a clinical dilemma. PURPOSE: This study was performed to
identify clinical characteristics of IPNs and develop a predictive model to
predict the risk of progression to pulmonary metastases in patients with
colorectal cancer. METHODS: We analyzed data from a prospectively collected
database involving 1195 patients with colorectal carcinoma who underwent curative
surgery between January 2008 and June 2010. A predictive model was constructed on
the basis of the probability risk score and validated in 115 patients collected
from a separate treatment period. RESULTS: Of the 1195 patients who underwent a
baseline staging chest computed tomography, 326 (27.2%) had IPNs. During a median
follow-up of 26.7 months (interquartile range: 18.0-37.2), 74 (28.1%) showed
pulmonary metastases. Five variables maintained prognostic significance after
multivariate analysis: metachronous nodule, bilateral involvement, positive
perineural invasion, increased number of positive lymph nodes, and rectal
location of cancer. The 2-year progression-free survival rates for the very low-,
low-, intermediate-, and high-risk groups were 96%, 82%, 46%, and 16%,
respectively (P < 0.001), with a concordance index of 0.81 (95% confidence
interval, 0.75-0.86). This model was validated in a separate patient set (P <
0.001), with a C-index of 0.83 (95% confidence interval, 0.77-0.88). CONCLUSIONS:
A predictive model for progression of IPNs may be clinically useful in
discriminating patients who might benefit from an aggressive surveillance program
and early pulmonary metastasectomies.
PMID- 25119122
TI - Abdominoperineal resection provides better local control but equivalent overall
survival to local excision of anorectal malignant melanoma: a systematic review.
AB - OBJECTIVE: To determine whether the extent of surgery is associated with survival
in anorectal malignant melanoma (ARMM). BACKGROUND: ARMM is a rare and highly
malignant neoplasm with unfavorable prognosis. The optimal surgical management,
abdominoperineal resection (APR) or local excision (LE), has been long debated,
but conclusive evidence has not been obtained. METHODS: A comprehensive
electronic literature search was performed to identify studies evaluating
survival between APR and LE for ARMM. The main outcome measures were overall
survival, relapse-free survival, and local recurrence. A meta-analysis was
performed using the random-effects models to calculate the odds ratios (ORs) and
95% confidence intervals (CIs). RESULTS: Thirty-one studies, with a total of 1006
patients [544 (54.1%) APR and 462 (45.9%) LE], were included. Meta-analyses
showed that overall survival (OR, 1.14; 95% CI, 0.74-1.76; P = 0.54) and relapse
free survival (OR, 0.95; 95% CI, 0.43-2.09; P = 0.89) did not differ
significantly between the APR and LE groups. APR significantly reduced local
recurrence compared with LE (OR, 0.18; 95% CI, 0.09-0.36; P < 0.00001).
CONCLUSIONS: Although several limitations, such as inclusion of only
retrospective studies with relatively small sample size and selection biases for
surgical procedure, are involved, this meta-analysis suggested that APR has no
survival benefit; however, APR confers better local control than LE. Given that
local failures after LE could be managed by salvage surgery, minimizing morbidity
and maximizing quality of life should be the focus in surgical treatment of ARMM.
PMID- 25119123
TI - Postoperative venous thromboembolism outcomes measure: analytic exploration of
potential misclassification of hospital quality due to surveillance bias.
PMID- 25119124
TI - Natural promoters of calcium oxalate monohydrate crystallization.
AB - Crystallization is often facilitated by modifiers that interact with specific
crystal surfaces and mediate the anisotropic rate of growth. Natural and
synthetic modifiers tend to function as growth inhibitors that hinder solute
attachment and impede the advancement of layers on crystal surfaces. There are
fewer examples of modifiers that operate as growth promoters, whereby modifier
crystal interactions accelerate the kinetic rate of crystallization. Here, we
examine two proteins, lysozyme and lactoferrin, which are observed in the organic
matrix of three types of pathological stones: renal, prostatic, and pancreatic
stones. This work focuses on the role of these proteins in the crystallization of
calcium oxalate monohydrate (COM), the most prominent constituent of human kidney
stones. Using a combination of experimental techniques, we show that these
proteins, which are rich in l-arginine and l-lysine amino acids, promote COM
growth. The synthesis and testing of peptides derived from contiguous segments of
lysozyme's primary amino acid sequence revealed subdomains within the protein
that operate either as an inhibitor or promoter of COM growth, with the latter
exhibiting efficacies that nearly match that of the protein. We observed that
cationic proteins promote COM growth over a wide range of modifier concentration,
which differs from calcification promoters in the literature that exhibit dual
roles as promoters and inhibitors at low and high concentration, respectively.
This seems to suggest a unique mechanism of action for lysozyme and lactoferrin.
Possible explanations for their effects on COM growth and crystal habit are
proposed on the basis of classical colloidal theories and the physicochemical
properties of peptide subdomains, including the number and spatial location of
charged or hydrogen-bonding moieties.
PMID- 25119125
TI - Factors behind negative attitudes toward cadaveric organ donation: a comparison
between medical and non-medical students in China: retraction.
PMID- 25119126
TI - National assessment of early biliary complications after liver transplantation:
economic implications.
AB - BACKGROUND: Despite improvement in surgical technique and medical management of
liver transplant recipients, biliary complications remain a frequent cause of
posttransplant morbidity and graft loss. Biliary complications require
potentially expensive interventions including radiologic procedures and surgical
revisions. METHODS: A national data set linking transplant registry and Medicare
claims data for 12,803 liver transplant recipients was developed to capture
information on complications, treatments, and associated direct medical costs up
to 3 years after transplantation. RESULTS: Biliary complications were more common
in recipients of donation after cardiac death compared to donation after brain
death allografts (23% vs. 19% P<0.001). Among donation after brain death
recipients, biliary complications were associated with $54,699 (95% confidence
interval [CI], $49,102 to $60,295) of incremental spending in the first year
after transplantation and $7,327 in years 2 and 3 (95% CI, $4,419-$10,236).
Biliary complications in donation after cardiac death recipients independently
increased spending by $94,093 (95% CI, $64,643-$124,542) in the first year and
$12,012 (95% CI, $-1,991 to $26,016) in years 2 and 3. CONCLUSION: This national
study of biliary complications demonstrates the significant economic impact of
this common perioperative complication and suggests a potential target for
quality of care improvements.
PMID- 25119127
TI - Time-to-referral, use, and efficacy of cardiac rehabilitation after heart
transplantation.
AB - BACKGROUND: Timely access, adherence, and efficacy of cardiac rehabilitation
programs (CRP) are important given the potential to mitigate or reverse the side
effects of immunosuppressive medications, weight gain, and cardiovascular
deconditioning that place heart transplant (HT) recipients at increased
cardiovascular risk. However, there is a dearth of information on use and
efficacy of CRPs. Therefore, we examined process indicators (time to referral and
correlates, program adherence) and clinical outcome indicators (functional
capacity (VO(2peak)), anthropometrics) of CR post-HT compared to post-coronary
artery bypass graft (CABG). METHODS: Baseline, 6-month exercise stress test
results, and anthropometrics were examined retrospectively among consecutively
enrolled post-HT and age-matched and sex-matched CABG patients. Time to referral
and program entry, attendance, and completion rates were also measured. RESULTS:
Heart transplant (n=43) and CABG patients were referred 24.9 +/- 48.9 and 2.1 +/-
3.6 months, respectively, after surgery (P=0.003). Once referred, there was no
difference in elapsed-time to program entry (P=0.2). There was a positive
relationship between time to referral and baseline waist circumference (r=0.5,
P=0.001), body mass index (r=0.5, P=0.002), hip circumference (r=0.4, P=0.008),
and body fat percentage (r=0.4, P=0.03) in HT. Heart transplant and CABG patients
had similar rates of CRP dropout (27.9% vs. 37.2% respectively, P=0.4). There was
improvement in VO(2peak) for HT (2.4 +/- 4.2 mL/kg/min; P=0.02) and CABG (5.5 +/-
5.4 mL/kg/min, P<0.001), but was greater for CABG (P=0.04). Anthropometric
measures remained stable for both cohorts (P>0.05). CONCLUSION: There is a
lengthy delay in time from HT to CRP referral, though once referred, gain
significant benefit in functional capacity. The appropriateness of this wait
needs to be elucidated; however, it appears that longer wait times are associated
with adverse effects on body composition.
PMID- 25119129
TI - The preferences and perspectives of nephrologists on patients' access to kidney
transplantation: a systematic review.
AB - We aimed to describe nephrologists' attitudes to patients' access to kidney
transplantation. Studies that assessed nephrologists' perspectives toward patient
referral, screening, and eligibility for kidney transplantation were synthesized.
Twenty-four studies (n>=4695) were included. Patients with comorbidities, were
nonadherent, of older age, ethnic minorities, or low socioeconomic status were
less likely to be recommended. Six themes underpinned nephrologists'
perspectives: prioritizing individual benefit and safety, maximizing efficiency,
patient accountability, justifying gains, protecting unit outcomes, and
reluctance to raise patients' expectations. Evidence-based guidelines may support
systematic and equitable decision-making. Interventions for high-risk or
disadvantaged patient populations could reduce disparities in access to
transplantation.
PMID- 25119128
TI - Lung transplantation for severe pulmonary hypertension--awake extracorporeal
membrane oxygenation for postoperative left ventricular remodelling.
AB - BACKGROUND: Bilateral lung transplantation (BLTx) is an established treatment for
end-stage pulmonary hypertension (PH). Ventilator weaning failure and death are
more common as in BLTx for other indications. We hypothesized that left
ventricular (LV) dysfunction is the main cause of early postoperative morbidity
or mortality and investigated a weaning strategy using awake venoarterial
extracorporeal membrane oxygenation (ECMO). METHODS: In 23 BLTx for severe PH,
ECMO used during BLTx was continued for a minimum of 5 days (BLTx-ECMO group).
Echocardiography, left atrial (LA) and Swan-Ganz catheters were used for
monitoring. Early extubation after transplantation was attempted under continued
ECMO. RESULTS: Preoperatively, all patients had severely reduced cardiac index
(mean, 2.1 L/min/m2). On postoperative day 2, reduction of ECMO flow resulted in
increasing LA and decreasing systemic blood pressures. On the day of ECMO
explantation (median, postoperative day 8), LV diameter had increased; LA and
blood pressures remained stable. Survival rates at 3 and 12 months were 100% and
96%, respectively. Data were compared to two historic control groups of BLTx
without ECMO (BLTx ventilation) or combined heart-lung transplantation for severe
PH. CONCLUSION: Early after BLTx for severe PH, the LV may be unable to handle
normalized LV preload. This can be effectively bridged with awake venoarterial
ECMO.
PMID- 25119130
TI - Extensively drug-resistant Pseudomonas aeruginosa bacteremia in solid organ
transplant recipients.
AB - BACKGROUND: We sought to determine the risk factors, molecular epidemiology,
antibiotic therapy, and outcomes of bacteremia because of extensively drug
resistant (XDR) Pseudomonas aeruginosa in solid organ transplant (SOT)
recipients. METHODS: All episodes of bacteremia occurring in SOT recipients were
prospectively documented from 2007 to 2013. RESULTS: Of 318 episodes of
bacteremia, 49 were caused by P. aeruginosa. Thirty-one strains (63%) were XDR
defined by nonsusceptibility to at least one agent in all but two or fewer
antipseudomonal antimicrobial categories. Time from transplantation to bacteremia
was shorter in XDR P. aeruginosa group comparing to other etiologies (median days
66 vs. 278; P=0.03). Factors independently associated with XDR P. aeruginosa
bacteremia were prior transplantation, nosocomial acquisition, and septic shock
at onset. XDR P. aeruginosa isolates belonged to a single clone (ST-175).
Comparing to other etiologies, patients with bacteremia because of XDR P.
aeruginosa more often received inadequate empirical antibiotic therapy.
Persistence of bacteremia, shock, respiratory failure and intensive care unit
admission were more frequent in patients with XDR P. aeruginosa. The overall case
fatality rate was higher among patients with XDR P. aeruginosa bacteremia than in
the others (38% vs. 16%; P=0.009). CONCLUSION: Bacteremia because of XDR P.
aeruginosa should be carefully considered when selecting empirical antibiotic
therapy for hospitalized SOT recipients with prior transplantation presenting
with septic shock.
PMID- 25119131
TI - The risk of cancer in recipients of living-donor, standard and expanded criteria
deceased donor kidney transplants: a registry analysis.
AB - BACKGROUND: Kidneys from expanded criteria deceased donors may elicit a strong
inflammatory response, predisposing recipients to an increased risk of cancer
after transplantation. We aimed to determine the association between donor types
and cancer risk after kidney transplantation. METHODS: Using the Australian and
New Zealand Dialysis and Transplant Registry, we assessed the association between
different donor types (living donor, standard, and expanded criteria deceased
donors) and the risk of cancer after kidney transplantation using adjusted Cox
proportional hazard and competing risk models. RESULTS: Over a median follow-up
period of 4.4 years in 7,040 patients (34,684 patient-years), 468 patients (6.6%)
developed cancer. The overall risks for cancer were 1,080, 1,444, and 2,018 per
100,000 patient-years for recipients of living donor, standard, and expanded
criteria deceased donor kidneys, respectively. Compared to recipients of living
donor kidneys, recipients of expanded criteria deceased donor kidneys were at an
increased risk of cancer (adjusted hazard ratio [HR], 1.52; 95% confidence
interval [95% CI], 1.15-2.02; P = 0.004), particularly for genitourinary cancer
(adjusted HR, 1.79; 95% CI, 1.03-3.10; P = 0.038) and post-transplant
lymphoproliferative disease (adjusted HR, 2.72; 95% CI, 1.38-5.37; P = 0.004).
CONCLUSION: Recipients of expanded criteria deceased donor kidneys are at
substantially increased risk of cancer, especially cancers with a viral etiology.
Allocation of expanded criteria deceased donor kidneys to potential recipients
should balance the harms, such as the excess risk of cancer against the survival
gains and quality-of-life benefits associated with transplantation.
PMID- 25119132
TI - Changes in circulating endothelial cells count could become a valuable tool in
the diagnostic definition of acute graft-versus-host disease.
AB - BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is
burdened by life-threatening complications, with graft-versus-host disease (GvHD)
being the major cause of morbility and mortality. Recently, clinical and
physiopathologic evidences showed that vascular endothelium can be a target of
GvHD in the early phase and circulating endothelial cells (CECs) represent
surrogate markers of endothelial damage. METHODS: Using the CellSearch System
(Veridex LLC, Raritan, NJ), CECs were counted before (T1), after conditioning
regimen (T2), at engraftment (T3), at GvHD onset (T4), and after steroid
treatment (T5) in 40 patients (7 Hodgkin's Disease, 13 Acute Myeloblastic
Leukemia, 5 Acute Lymphoblastic Leukemia, 8 Multiple Myeloma, 3 Chronic
Lymphocytic Leukemia, 1 Non-Hodgkin Lymphoma, 1 Chronic Myeloid Leukemia, 2
Severe Aplastic Anemia) undergoing allo-HSCT. RESULTS: The median CEC per
milliliter at T1 was 20 (n=33, range 4-718), in comparison to a value of 2
(range, 1-14) in controls (P<0.001). At T3, CEC per milliliter were 47 (range, 16
148) in GvHD patients and 92 (range, 23-276) in patients without GvHD (P=0.006).
This difference remained significant in multivariate analysis (odds ratio, 0.97;
95% confidence interval, 0.96-0.99; P=0.02). At GvHD onset, the relative increase
of CEC counts from time of engraftment (T4 vs. T3) was 44% (range, -43% to 569%)
in GvHD patients versus 0% (range, -49% to 2%) in patients without GvHD
(P=0.003), being confirmed as significant in multivariate analysis (odds ratio,
1.04; 95% confidence interval, 1.0-1.08; P=0.04). CONCLUSION: Changes in CEC
count can represent a promising marker to monitor endothelial damage in patients
undergoing allo-HSCT and could become a valuable tool in the diagnostic
definition of GvHD.
PMID- 25119133
TI - A novel simple noninvasive index to predict renal transplant acute rejection by
contrast-enhanced ultrasonography.
AB - PURPOSE: This study aimed to evaluate the application of quantitative contrast
enhanced ultrasonography (CEUS) in the assessment of renal allograft dysfunction
and to establish a new noninvasive index to predict acute rejection (AR).
METHODS: Fifty-seven renal transplant recipients were enrolled in this
prospective study. Before renal allograft biopsy, CEUS examinations were
performed.The biopsy results proved 23 cases of AR (AR group), 10 cases of acute
tubular necrosis (ATN group), and 24 with normal evolution (stable group).
Contrast-enhanced ultrasonography parameters including rising time (RT), time to
peak (TTP), and the delta-time among regions of interest (DeltaRT and DeltaTTP)
were analyzed. RESULTS: In the AR group, RT and TTP of interlobar artery and
medulla (RTi, RTm, TTPi, and TTPm) as well as DeltaRT and DeltaTTP between
medulla and cortex (DeltaRTm-c and DeltaTTPm-c) were significantly higher
compared with those in the stable group. RTm and TTPm as well as DeltaRTm-c and
DeltaTTPm-c were remarkably higher compared with those in the ATN group. DeltaRTm
c and estimated glomerular filtration rate (eGFR) were identified as independent
predictors by multivariate analysis (P = 0.008 and P = 0.024). On the basis of
the multivariate analysis results and area under the receiver operating
characteristic curves of individual markers, we constructed a new simple index, P
= -0.587 + 0.286 *DeltaRTm-c - 0.028 * eGFR; new index = e(P)/(1 + e(P)), to
discriminate AR, which had better area under the receiver operating
characteristic curves than eGFR or individual CEUS parameters. CONCLUSION:
Contrast-enhanced ultrasonography parameters are reliable markers for
differentiating the perfusion status of transplanted kidneys. Furthermore, the
new simple index can easily predictAR with a high degree of accuracy.
PMID- 25119135
TI - Ion pairing: from water clusters to the aqueous bulk.
PMID- 25119134
TI - The outcomes of simultaneous liver and kidney transplantation using donation
after cardiac death organs.
AB - BACKGROUND: There has been a remarkable increase in simultaneous liver and kidney
transplantations (SLK). As organ demand has increased, so has the use of donation
after cardiac death (DCD). However, little is known about the outcomes of DCD in
SLK. METHODS: We performed a retrospective analysis using the United Network for
Organ Sharing database to compare the outcomes of DCD SLK to donation after brain
death (DBD) and determine the impact of donor and recipient factors on allograft
and patient survival. RESULTS: Between 2002 and 2011, a total of 3,026 subjects
received SLK from DBD and 98 from DCD. Kidney, liver, and patient survival from
DCD donors were inferior to DBD at 1, 3, and 5 years (P=0.0056, P=0.0035, and
P=0.0205, respectively). With the use of the Cox model, DCD was a significant
risk factor for kidney and liver allograft failure and patient mortality.
Recipient factors that were associated with worse allograft and patient outcomes
included black race, diabetes, being on a ventilator, hospitalization, delayed
graft function, hepatocellular carcinoma, and intensive care unit stay. Older age
of the donor was also associated with worse outcomes. CONCLUSION: Despite the
decreased allograft and patient survival compared with DBD, DCD SLK provides an
acceptable option for SLK, with a survival probability of more than 50% at 5
years.
PMID- 25119136
TI - The p53-reactivating small molecule RITA induces senescence in head and neck
cancer cells.
AB - TP53 is the most commonly mutated gene in head and neck cancer (HNSCC), with
mutations being associated with resistance to conventional therapy. Restoring
normal p53 function has previously been investigated via the use of RITA
(reactivation of p53 and induction of tumor cell apoptosis), a small molecule
that induces a conformational change in p53, leading to activation of its
downstream targets. In the current study we found that RITA indeed exerts
significant effects in HNSCC cells. However, in this model, we found that a
significant outcome of RITA treatment was accelerated senescence. RITA-induced
senescence in a variety of p53 backgrounds, including p53 null cells. Also,
inhibition of p53 expression did not appear to significantly inhibit RITA-induced
senescence. Thus, this phenomenon appears to be partially p53-independent.
Additionally, RITA-induced senescence appears to be partially mediated by
activation of the DNA damage response and SIRT1 (Silent information regulator T1)
inhibition, with a synergistic effect seen by combining either ionizing radiation
or SIRT1 inhibition with RITA treatment. These data point toward a novel
mechanism of RITA function as well as hint to its possible therapeutic benefit in
HNSCC.
PMID- 25119137
TI - Topical, Non-Medicated LOYON((r)) in Facilitating the Removal of Scaling in
Infants and Children with Cradle Cap: a Proof-of-Concept Pilot Study.
AB - INTRODUCTION: Cradle cap is a very common condition in infants that presents as
greasy, scaly patches on the scalp within the first weeks of life. Although
usually disappearing by itself, the condition worries parents because of its
appearance. When removing the scales, it is crucial to prevent spot bleedings to
avoid infections. The investigational medical device LOYON((r)) (Cetiol((r)) CC,
dimethicone) solution (G. Pohl-Boskamp GmbH & Co. KG, Hohenlockstedt, Germany)
has the potential to meet these needs since it removes scales gently. It was,
therefore, the aim of this proof-of-concept study to assess the efficacy and
safety of topically applied, non-medicated LOYON((r)) in facilitating the removal
of scaling in infants and children with cradle cap without inducing spot
bleedings. METHODS: This single-center, open, proof-of-concept, pilot study was
conducted in 20 male or female infants/children aged 3-36 months with clinically
diagnosed cradle cap. The 8-day study period included one to three applications
of LOYON((r)). Clinical assessment of scaling and secondary parameters was
performed at baseline and after treatment. Adverse events were recorded. A
questionnaire on subjective efficacy and usability was handed out to the parents.
RESULTS: With a maximum of three applications of LOYON((r)) applied to 20
subjects, a reduction in scaling intensity from moderate or severe to very mild
or mild was achieved in 80% of the subjects. Treatment success, defined as the
reduction of the scaling baseline score by at least two points, was achieved in
50% of subjects. Results of this study do not indicate any safety concern. No
spot bleedings were observed. LOYON((r)) was generally well tolerated and overall
treatment was rated as "good" by the parents/legal guardians. CONCLUSION: This
study suggests that LOYON((r)) is well tolerated, safe and effective in
facilitating the removal of scaling in infants and children with cradle cap. With
its gentle approach and rapid effect, LOYON((r)) thus represents a good
alternative to home remedies for treatment of cradle cap.
PMID- 25119139
TI - Analysis of the aggregation of an anionic porphyrin with a cationic surfactant at
the supercritical carbon dioxide-water interface using UV-visible external
reflection spectrometry.
AB - An external reflection (ER) spectrometric device was developed to directly
measure adsorbates at the supercritical carbon dioxide (SC-CO2)-water interface.
The aggregation of diprotonated species of 5,10,15,20-tetraphenyl-21H,23H
porphinetetrasulfonic acid (H4tpps(2-)) at the positively charged SC-CO2-water
interface, prepared by adsorption by the cetyltrimethylammonium ion (CTA(+)), was
studied using this device. Orientations of the H4tpps(2-) monomers and J
aggregates at the SC-CO2-water interface were assessed using s- and p-polarized
external reflection (ER) spectra. It appeared that the porphyrin plane of the
H4tpps(2-) monomer was nearly parallel to the SC-CO2-water interface, and that
the long axis of the rod-like H4tpps(2-) J-aggregate was also nearly parallel to
the interface. Dependence of the ER spectra on CTA(+) concentration and CO2
pressure were investigated, and the interfacial CTA(+) concentration was found to
cause changes in the interfacial H4tpps(2-) species present. Increasing the CO2
pressure changed the interfacial species from the H4tpps(2-) monomer to the
H4tpps(2-) J-aggregate because the interfacial CTA(+) concentration increased as
the pressure increased. This suggests that the interfacial chemical species can
be changed by controlling the pressure and temperature of the SC-CO2. This is the
first report of direct measurements of the chemical species at the SC-CO2-water
interface, as far as we know.
PMID- 25119140
TI - Characterization of the peer review network at the Center for Scientific Review,
National Institutes of Health.
AB - The National Institutes of Health (NIH) is the largest source of funding for
biomedical research in the world. This funding is largely effected through a
competitive grants process. Each year the Center for Scientific Review (CSR) at
NIH manages the evaluation, by peer review, of more than 55,000 grant
applications. A relevant management question is how this scientific evaluation
system, supported by finite resources, could be continuously evaluated and
improved for maximal benefit to the scientific community and the taxpaying
public. Towards this purpose, we have created the first system-level description
of peer review at CSR by applying text analysis, bibliometric, and graph
visualization techniques to administrative records. We identify otherwise latent
relationships across scientific clusters, which in turn suggest opportunities for
structural reorganization of the system based on expert evaluation. Such studies
support the creation of monitoring tools and provide transparency and knowledge
to stakeholders.
PMID- 25119138
TI - A comparative study of techniques for differential expression analysis on RNA-Seq
data.
AB - Recent advances in next-generation sequencing technology allow high-throughput
cDNA sequencing (RNA-Seq) to be widely applied in transcriptomic studies, in
particular for detecting differentially expressed genes between groups. Many
software packages have been developed for the identification of differentially
expressed genes (DEGs) between treatment groups based on RNA-Seq data. However,
there is a lack of consensus on how to approach an optimal study design and
choice of suitable software for the analysis. In this comparative study we
evaluate the performance of three of the most frequently used software tools:
Cufflinks-Cuffdiff2, DESeq and edgeR. A number of important parameters of RNA-Seq
technology were taken into consideration, including the number of replicates,
sequencing depth, and balanced vs. unbalanced sequencing depth within and between
groups. We benchmarked results relative to sets of DEGs identified through either
quantitative RT-PCR or microarray. We observed that edgeR performs slightly
better than DESeq and Cuffdiff2 in terms of the ability to uncover true
positives. Overall, DESeq or taking the intersection of DEGs from two or more
tools is recommended if the number of false positives is a major concern in the
study. In other circumstances, edgeR is slightly preferable for differential
expression analysis at the expense of potentially introducing more false
positives.
PMID- 25119141
TI - Potassium-sulfur batteries: a new member of room-temperature rechargeable metal
sulfur batteries.
AB - We report room-temperature rechargeable potassium-sulfur (K-S) batteries using
ordered mesoporous carbon (CMK-3)/sulfur and polyanilime (PANI) coated CMK
3/sulfur composites as the cathode and metallic potassium as the anode. The
electrochemical reaction mechanism was investigated by electrochemical tests,
TEM, XRD, and Raman spectra. It was found that K-S batteries delivered two
reduction peaks located at about 2.1 and 1.8 V and one oxidation peak at about
2.2 V, respectively. Meanwhile, K2S3 was the major discharge product that could
be charged to reversibly form S and K ion. Through optimization of sulfur
content, the CMK-3/sulfur composite with 40.8 wt % S displayed an initial
discharge capacity of 512.7 mAh g(-1) and a capacity of 202.3 mAh g(-1) after 50
cycles at a current density of 50 mA g(-1). A coating of conductive polyanilime
(PANI) on the CMK-3/sulfur composite is effective in enhancing the cycling
performance. In comparison, PANI@CMK-3/sulfur composite showed a capacity of
329.3 mAh g(-1) after 50 cycles at 50 mA g(-1). The results shed light on the
basic study of rechargeable K-S batteries.
PMID- 25119142
TI - Povarov-type reaction using methyl as new input: direct synthesis of substituted
quinolines by I2-mediated formal [3 + 2 + 1] cycloaddition.
AB - A highly efficient molecular iodine mediated formal [3 + 2 + 1] cycloaddition
reaction for the direct synthesis of substituted quinolines from methyl ketones,
arylamines, and styrenes is developed. The methyl group of the methyl ketone
represents uniquely reactive input in the Povarov reaction. A self-sequenced
iodination/Kornblum oxidation/Povarov/aromatization mechanism has been proposed
as a possible reaction sequence to account for the results observed in this
study.
PMID- 25119143
TI - Multiscale modeling of the electrostatic impact of self-assembled monolayers used
as gate dielectric treatment in organic thin-film transistors.
AB - This study sheds light on the microscopic mechanisms by which self-assembled
monolayers (SAMs) determine the onset voltage in organic thin-film transistors
(OTFTs). Experiments and modeling are combined to investigate the self-assembly
and electrostatic interaction processes in prototypical OTFT structures
(SiO2/SAM/pentacene), where alkylated and fluoroalkylated silane SAMs are
compared. The results highlight the coverage-dependent impact of the SAM on the
density of semiconductor states and enable the rationalization and the control of
the OTFT characteristics.
PMID- 25119144
TI - Do the ends justify the means? A test of alternatives to the FDA proposed
cigarette warning labels.
AB - Three studies provide empirical, social scientific tests of alternatives to the
originally proposed U.S. Food and Drug Administration (FDA) cigarette package
warning labels on health risk beliefs, perceived fear, and effectiveness. Our
research addresses questions at the root of the legal disputes surrounding FDA
regulation of cigarette package warning labels. Specifically, we describe results
from three studies that investigate the mediating role of health beliefs and
perceived fear in shaping message effectiveness and intentions to quit. The first
study featured nonsmoking young adults, while the second and third studies
sampled adult daily smokers. Each study was a randomized experiment with five
warning-label image conditions: full-color graphic warning labels, black-and
white graphic warning labels, warning text (no graphic image), Surgeon General's
warning labels, and no warning. Results consistently indicate that graphic
warning labels (in both color and black-and-white) promote increased perceptions
of fear, which in turn are associated with greater (perceived and actual)
effectiveness. We conclude with a discussion of the results, highlighting
implications, public policy considerations, and suggestions for future research.
PMID- 25119145
TI - Disturbed cortico-amygdalar functional connectivity as pathophysiological
correlate of working memory deficits in bipolar affective disorder.
AB - Patients suffering from bipolar affective disorder show deficits in working
memory functions. In a previous functional magnetic resonance imaging study, we
observed an abnormal hyperactivity of the amygdala in bipolar patients during
articulatory rehearsal in verbal working memory. In the present study, we
investigated the dynamic neurofunctional interactions between the right amygdala
and the brain systems that underlie verbal working memory in both bipolar
patients and healthy controls. In total, 18 euthymic bipolar patients and 18
healthy controls performed a modified version of the Sternberg item-recognition
(working memory) task. We used the psychophysiological interaction approach in
order to assess functional connectivity between the right amygdala and the brain
regions involved in verbal working memory. In healthy subjects, we found
significant negative functional interactions between the right amygdala and
multiple cortical brain areas involved in verbal working memory. In comparison
with the healthy control subjects, bipolar patients exhibited significantly
reduced functional interactions of the right amygdala particularly with the right
hemispheric, i.e., ipsilateral, cortical regions supporting verbal working
memory. Together with our previous finding of amygdala hyperactivity in bipolar
patients during verbal rehearsal, the present results suggest that a disturbed
right-hemispheric "cognitive-emotional" interaction between the amygdala and
cortical brain regions underlying working memory may be responsible for amygdala
hyperactivation and affects verbal working memory (deficits) in bipolar patients.
PMID- 25119148
TI - Darzens reaction rate enhancement using aqueous media leading to a high level of
kinetically controlled diastereoselective synthesis of steroidal epoxyketones.
AB - Darzens reactions between halocarbonyls and aldehydes have been carried out in
water in the presence of a Li(+)-containing base, a phase-transfer catalyst, and
granular polytetrafluoroethylene under mechanical stirring. Reactions using both
aromatic and aliphatic aldehydes produced epoxides stereoselectively in good to
excellent yields. This is the first time that aliphatic aldehydes with alpha-H
have been used in aqueous Darzens reactions. The Darzens reactions were much
faster in water than in organic solvents. This aqueous rate enhancement occurred
for Darzens reactions between enantiopure steroidal haloketones and aldehydes,
yielding enantiopure spiroepoxides with a high level of kinetically controlled
diastereoselectivity. Chromatography was avoided in the purifications of the
steroidal spiroepoxides. This is an example of preparing enantiopure epoxyketones
via aqueous Darzens reaction using chiral alpha-haloketone substrates.
PMID- 25119147
TI - Development and evaluation of magnetic microemulsion: tool for targeted delivery
of camptothecin to BALB/c mice-bearing breast cancer.
AB - PURPOSE: Development and evaluation of camptothecin-loaded-microemulsion (ME) and
-magnetic microemulsion (MME) for passive/active-targeted delivery to BALB/c mice
bearing breast cancer. METHODS: Based on the pseudo-ternary phase diagrams
camptothecin-loaded-MEs and -MMEs were developed using benzyl alcohol:Captex 300
(3:1), TPGS:Tween 80 (2:1) and water. Furthermore, characterized for their
droplet size distribution, magnetic susceptibility and effect of droplet size in
plasma and evaluated for in vitro and in vivo targeting potential, drug release,
haemolytic potential, cytotoxicity, genotoxicity, in vivo biodistribution and
lactone ring stability. RESULTS: Drug-loaded MEs showed uniform droplet
distribution, extended drug release (76.07 +/- 4.30% at 24 h), acceptable level
of haemolytic activity (<20%), significant cytotoxicity (129 +/- 3.9 ng/mL)
against MCF-7 cancer cells and low DNA damage in lymphocytes. Targeting potential
of MMEs was documented in 4T1 breast cancer-induced BALB/c mice. MMEs were
concentrated more at the target tissue on introduction of external magnetic
field. In vivo biodistribution study documented the active targeting of 5067.56
+/- 354.72 ng/gm and passive targeting of 1677.58 +/- 134.20 ng/gm camptothecin
to breast cancer from MME and ME, respectively. Lactone stability study shows
around 80% of the lactone stable at 24 h. CONCLUSIONS: Developed ME and MME may
act as a promising nanocarrier for efficient targeting of breast cancer tissues.
PMID- 25119146
TI - DSM-5 reviewed from different angles: goal attainment, rationality, use of
evidence, consequences--part 1: general aspects and paradigmatic discussion of
depressive disorders.
AB - DSM-5 was published in 2013 after about 10 years of preparation. Part 1 of this
paper discusses several more general aspects of DSM-5 and offers a detailed,
paradigmatic analysis of changes made to the chapter on depressive disorders. The
background for the changes is analysed on the basis of a PubMed search and review
papers on the classification of mental disorders in general and on empirical
knowledge about individual disorders. Contrary to the original plans, DSM-5 has
not introduced a primarily dimensional diagnostic system but has widely preserved
the categorical system of disorders. Also, it has not adopted a more
neurobiological approach to disorders by including biological markers to increase
the objectivity of psychiatric diagnoses but has maintained the primarily symptom
based, descriptive approach. The criteria for some disorders have been changed,
including affective, schizophrenic and addiction disorders, and a few new
disorders have been added. A minimal version of the dimensional approach was
realised through the introduction of several transnosological specifiers and the
option to make symptom- or syndrome-related severity and dimensional assessments.
These specifiers and assessments might allow a more individualised description of
a patient's psychopathological state and more personalised treatment. However,
most of the symptom- and syndrome-related assessments are not mandatory and
therefore may not be used in clinical practice.
PMID- 25119149
TI - Controlled stripes of ultrafine ferroelectric domains.
AB - In the pursuit of ferroic-based (nano)electronics, it is essential to minutely
control domain patterns and domain switching. The ability to control domain
width, orientation and position is a prerequisite for circuitry based on fine
domains. Here, we develop the underlying theory towards growth of ultra-fine
domain patterns, substantiate the theory by numerical modelling of practical
situations and implement the gained understanding using the most widely applied
ferroelectric, Pb(Zr,Ti)O3, demonstrating controlled stripes of 10 nm wide
domains that extend in one direction along tens of micrometres. The observed
electrical conductivity along these thin domains embedded in the otherwise
insulating film confirms their potential for electronic applications.
PMID- 25119151
TI - Bani Adam: Saadi Shirazi (AD 1184-1283/1291) and the concept of empathy.
PMID- 25119150
TI - Temporal and spatial distribution of the aquaporin 1 in spinal cord and dorsal
root ganglia after traumatic injuries of the sciatic nerve.
AB - PURPOSE: The aquaporin family comprises a large family of integral membrane
proteins that enable the movement of water and other small, neutral solutes
across plasma membranes. Although function and mechanism of aquaporins in central
nervous system injury have been reported, the pathophysiologic role of aquaporin
1 (AQP1) in peripheral nerve has not been extensively documented. In the present
study, we aimed to study the temporal and spatial distribution of AQP1 in spinal
cord and dorsal root ganglia after sciatic nerve injury. METHODS: Forty-eight
adult female mice were randomly divided into four groups (intact controls, sham
operated, cut injury, and crush injury). Animals receiving cut or crush injuries
were sacrificed at the 2nd, 24th, and 48th postoperative hours. Spinal cord
samples at the level of lumbosacral intumescences and corresponding dorsal root
ganglia on the experimental and contralateral side were dissected free and
proceeded to AQP1 immunohistochemistry. RESULTS: Our quantitative estimations
revealed that a sharp increase in AQP1 immunoreactivity at the 24th postoperative
hour was observed. This sharp increase was no more evident at 48 h after sciatic
nerve injury. Identical peak was observed after both cut and crush injuries.
CONCLUSIONS: We demonstrated that there was a temporal relationship with an
increased expression of AQP1 following injury sustained to the sciatic nerve that
was significantly observed in dorsal root ganglia and spinal cord. Those
expressions were also subsided over time.
PMID- 25119152
TI - A hybrid technique for ventriculoatrial shunt implantation--technical note.
AB - PURPOSE: The aim of the article is to present the new hybrid technique for
ventriculoatrial shunt implantation. METHODS: Two-and-a-half-year-old boy needed
ventriculoatrial shunt implantation due to communicating hydrocephalus and
impaired absorptive ability of the peritoneum. Because of a complete occlusion of
the right internal jugular vein and critical stenosis of a distal part of the
left internal jugular vein, the procedure was performed under fluoroscopy
guidance in the catheterisation laboratory equipped with a 3-dimensional single
plane angiography machine (Philips Allura--The Netherlands). At the level of
critical stenosis of the left jugular vein, it was decided to perform a
percutaneous venous balloon angioplasty. This procedure allowed inserting the
ventriculoatrial shunt into the right atrium. RESULTS: The whole postoperative
period was uneventful. Now, the child is free from symptoms of increased
intracranial pressure. The boy has been followed for 9 months. In the control MRI
examination, the ventricular system did not change as compared with the previous
study. CONCLUSION: The disadvantage of the hemodynamic technique is a higher dose
of X-ray irradiation in comparison to other techniques. The hybrid technique
should be reserved only to very complicated cases.
PMID- 25119154
TI - The importance of radiation worker studies.
PMID- 25119153
TI - Neurocutaneous melanosis is associated with tethered spinal cord.
AB - PURPOSE: Neurocutaneous melanosis (NCM) is a rare congenital disorder occurring
in children born with multiple or large congenital melanocytic nevi (CMN) in
association with melanocytic deposits in the leptomeninges. Multiple associations
between NCM and other syndromes or neurologic abnormalities have been reported.
Of note, there exists a possible association between NCM and tethered cord (TC).
METHODS: We retrospectively reviewed charts and films of all patients with the
diagnosis of NCM at the Children's Hospital of Pittsburgh (CHP) from August 2002
to present. RESULTS: Five children met the criteria for NCM at our institution
over a 12-year period. Apart from the melanocytic deposits, one or more
additional spinal abnormalities were identified in all children. Three children
had radiographic evidence of a low-lying conus medullaris, two of which also
demonstrated lipomatous infiltration of the filum terminale, consistent with a
tethered cord (TC). CONCLUSIONS: Clinical features of NCM include dermatologic
and neurologic manifestations. To date, this is the first series to note an
association between NCM and TC. While nearly all recent series of NCM patients
advocate early MRI of the neuroaxis, we recommend screening imaging of the spine
on children with possible NCM regardless of the locations of CMN.
PMID- 25119156
TI - Reference selection influences the reliability of conclusions.
PMID- 25119158
TI - Magnetic resonance imaging in acute hamstring injury: can we provide a return to
play prognosis?
AB - BACKGROUND: Sports physicians are increasingly requested to perform magnetic
resonance imaging (MRI) of acute hamstring muscle injuries and to provide a
prognosis of the time to return to play (RTP) on the basis of their findings.
OBJECTIVES: To systematically review the literature on the prognostic value of
MRI findings for time to RTP in acute hamstring muscle injuries. DATA SOURCES:
The databases of PubMed, EMBASE, CINAHL, Web of Science and Cochrane Library were
searched in June 2013. STUDY ELIGIBILITY CRITERIA: Studies evaluating MRI as a
prognostic tool for determining time to RTP in athletes with acute hamstring
injuries were eligible for inclusion. DATA ANALYSIS: Two authors independently
screened the search results and assessed risk of bias using criteria for quality
appraisal of prognosis studies. A best-evidence synthesis was used to identify
the level of evidence. RESULTS: Of the 12 studies included, one had a low risk of
bias and 11 a high risk of bias. There is moderate evidence that injuries without
hyperintensity on fluid-sensitive sequences are associated with a shorter time to
RTP and that injuries involving the proximal free tendon are associated with a
longer time to RTP. Limited evidence was found for an association of central
tendon disruption, injury not affecting the musculotendinous junction and a total
rupture with a longer time to RTP. The other MRI findings studied showed either
no association or there was conflicting evidence. CONCLUSION: There is currently
no strong evidence for any MRI finding that gives a prognosis on the time to RTP
after an acute hamstring injury, owing to considerable risks of bias in the
studies on this topic.
PMID- 25119157
TI - Cooling athletes with a spinal cord injury.
AB - Cooling strategies that help prevent a reduction in exercise capacity whilst
exercising in the heat have received considerable research interest over the past
3 decades, especially in the lead up to a relatively hot Olympic and Paralympic
Games. Progressing into the next Olympic/Paralympic cycle, the host, Rio de
Janeiro, could again present an environmental challenge for competing athletes.
Despite the interest and vast array of research into cooling strategies for the
able-bodied athlete, less is known regarding the application of these cooling
strategies in the thermoregulatory impaired spinal cord injured (SCI) athletic
population. Individuals with a spinal cord injury (SCI) have a reduced afferent
input to the thermoregulatory centre and a loss of both sweating capacity and
vasomotor control below the level of the spinal cord lesion. The magnitude of
this thermoregulatory impairment is proportional to the level of the lesion. For
instance, individuals with high-level lesions (tetraplegia) are at a greater risk
of heat illness than individuals with lower-level lesions (paraplegia) at a given
exercise intensity. Therefore, cooling strategies may be highly beneficial in
this population group, even in moderate ambient conditions (~21 degrees C). This
review was undertaken to examine the scientific literature that addresses the
application of cooling strategies in individuals with an SCI. Each method is
discussed in regards to the practical issues associated with the method and the
potential underlying mechanism. For instance, site-specific cooling would be more
suitable for an athlete with an SCI than whole body water immersion, due to the
practical difficulties of administering this method in this population group.
From the studies reviewed, wearing an ice vest during intermittent sprint
exercise has been shown to decrease thermal strain and improve performance. These
garments have also been shown to be effective during exercise in the able-bodied.
Drawing on additional findings from the able-bodied literature, the combination
of methods used prior to and during exercise and/or during rest periods/half-time
may increase the effectiveness of a strategy. However, due to the paucity of
research involving athletes with an SCI, it is difficult to establish an optimal
cooling strategy. Future studies are needed to ensure that research outcomes can
be translated into meaningful performance enhancements by investigating cooling
strategies under the constraints of actual competition. Cooling strategies that
meet the demands of intermittent wheelchair sports need to be identified, with
particular attention to the logistics of the sport.
PMID- 25119159
TI - Effect of (a)synchronous light fluctuation on diversity, functional and
structural stability of a marine phytoplankton metacommunity.
AB - Disentangling the mechanisms that maintain the stability of communities and
ecosystem properties has become a major research focus in ecology in the face of
anthropogenic environmental change. Dispersal plays a pivotal role in maintaining
diversity in spatially subdivided communities, but only a few experiments have
simultaneously investigated how dispersal and environmental fluctuation affect
community dynamics and ecosystem stability. We performed an experimental study
using marine phytoplankton species as model organisms to test these mechanisms in
a metacommunity context. We established three levels of dispersal and exposed the
phytoplankton to fluctuating light levels, where fluctuations were either
spatially asynchronous or synchronous across patches of the metacommunity.
Dispersal had no effect on diversity and ecosystem function (biomass), while
light fluctuations affected both evenness and community biomass. The temporal
variability of community biomass was reduced by fluctuating light and temporal
beta diversity was influenced interactively by dispersal and fluctuation, whereas
spatial variability in community biomass and beta diversity were barely affected
by treatments. Along the establishing gradient of species richness and dominance,
community biomass increased but temporal variability of biomass decreased, thus
highest stability was associated with species-rich but highly uneven communities
and less influenced by compensatory dynamics. In conclusion, both specific traits
(dominance) and diversity (richness) affected the stability of metacommunities
under fluctuating conditions.
PMID- 25119155
TI - Physical activity, air pollution and the brain.
AB - This review introduces an emerging research field that is focused on studying the
effect of exposure to air pollution during exercise on cognition, with specific
attention to the impact on concentrations of brain-derived neurotrophic factor
(BDNF) and inflammatory markers. It has been repeatedly demonstrated that regular
physical activity enhances cognition, and evidence suggests that BDNF, a
neurotrophin, plays a key role in the mechanism. Today, however, air pollution is
an environmental problem worldwide and the high traffic density, especially in
urban environments and cities, is a major cause of this problem. During exercise,
the intake of air pollution increases considerably due to an increased
ventilation rate and particle deposition fraction. Recently, air pollution
exposure has been linked to adverse effects on the brain such as cognitive
decline and neuropathology. Inflammation and oxidative stress seem to play an
important role in inducing these health effects. We believe that there is a need
to investigate whether the well-known benefits of regular physical activity on
the brain also apply when physical activity is performed in polluted air. We also
report our findings about exercising in an environment with ambient levels of air
pollutants. Based on the latter results, we hypothesize that traffic-related air
pollution exposure during exercise may inhibit the positive effect of exercise on
cognition.
PMID- 25119161
TI - Production of arachidonic and eicosapentaenoic acids by the marine oomycete
Halophytophthora.
AB - Polyunsaturated fatty acids (PUFAs) are fatty acids with more than one double
bond in the chemical structure. Arachidonic acid (ARA, 20:4 (n-6)) and
eicosapentaenoic acid (EPA, 22:5 (n-3)) are common PUFAs with beneficial health
effects. Marine fish and meat are the main sources of omega-3 and omega-6 fatty
acids in human's diet, respectively. In particular, there is a general decline in
fish catch, implicating the need for an alternative source of omega-3 fatty
acids. Previous studies have examined the production of polyunsaturated fatty
acids including ARA and EPA by various microorganisms, including microalgae,
fungi, and thraustochytrids. In this study, the production of ARA and EPA by 10
isolates of four estuarine Halophytophthora species (Halophytophthora avicenniae,
Halophytophthora polymorphica, Halophytophthora vesicula, and Halophytophthora
spinosa var. spinosa) cultured from fallen mangrove leaves in Taiwan was
examined. The yield of ARA ranged from 0.004 to 0.052 g/L with the highest yield
of ARA obtained from H. spinosa var. spinosa IMB162, but no or a very low level
of EPA was produced by IMB162. For EPA production by Halophytophthora spp., the
yield ranged from 0 to 0.047 g/L. Percentage of ARA in total fatty acid ranged
between 7.16 and 25.02%. One-way ANOVA analysis using Tukey Test (p >= 0.05)
suggested that there is significant difference in the percentage of EPA in total
fatty acid produced by the isolates, which ranged from 0.01 to 18.42%. BODIPY
505/515 fluorescent staining suggests that lipid bodies were evenly distributed
in the mycelia of Halophytophthora species.
PMID- 25119160
TI - A tree-ring perspective on the terrestrial carbon cycle.
AB - Tree-ring records can provide valuable information to advance our understanding
of contemporary terrestrial carbon cycling and to reconstruct key metrics in the
decades preceding monitoring data. The growing use of tree rings in carbon-cycle
research is being facilitated by increasing recognition of reciprocal benefits
among research communities. Yet, basic questions persist regarding what tree
rings represent at the ecosystem level, how to optimally integrate them with
other data streams, and what related challenges need to be overcome. It is also
apparent that considerable unexplored potential exists for tree rings to refine
assessments of terrestrial carbon cycling across a range of temporal and spatial
domains. Here, we summarize recent advances and highlight promising paths of
investigation with respect to (1) growth phenology, (2) forest productivity
trends and variability, (3) CO2 fertilization and water-use efficiency, (4)
forest disturbances, and (5) comparisons between observational and computational
forest productivity estimates. We encourage the integration of tree-ring data:
with eddy-covariance measurements to investigate carbon allocation patterns and
water-use efficiency; with remotely sensed observations to distinguish the timing
of cambial growth and leaf phenology; and with forest inventories to develop
continuous, annually-resolved and long-term carbon budgets. In addition, we note
the potential of tree-ring records and derivatives thereof to help evaluate the
performance of earth system models regarding the simulated magnitude and dynamics
of forest carbon uptake, and inform these models about growth responses to (non
)climatic drivers. Such efforts are expected to improve our understanding of
forest carbon cycling and place current developments into a long-term
perspective.
PMID- 25119162
TI - Predicted effects of gypsy moth defoliation and climate change on forest carbon
dynamics in the New Jersey pine barrens.
AB - Disturbance regimes within temperate forests can significantly impact carbon
cycling. Additionally, projected climate change in combination with multiple,
interacting disturbance effects may disrupt the capacity of forests to act as
carbon sinks at large spatial and temporal scales. We used a spatially explicit
forest succession and disturbance model, LANDIS-II, to model the effects of
climate change, gypsy moth (Lymantria dispar L.) defoliation, and wildfire on the
C dynamics of the forests of the New Jersey Pine Barrens over the next century.
Climate scenarios were simulated using current climate conditions (baseline), as
well as a high emissions scenario (HadCM3 A2 emissions scenario). Our results
suggest that long-term changes in C cycling will be driven more by climate change
than by fire or gypsy moths over the next century. We also found that simulated
disturbances will affect species composition more than tree growth or C
sequestration rates at the landscape level. Projected changes in tree species
biomass indicate a potential increase in oaks with climate change and gypsy moth
defoliation over the course of the 100-year simulation, exacerbating current
successional trends towards increased oak abundance. Our research suggests that
defoliation under climate change may play a critical role in increasing the
variability of tree growth rates and in determining landscape species composition
over the next 100 years.
PMID- 25119163
TI - Reduction in the size of enlarged pelvic lymph nodes after chemoradiation therapy
is associated with fewer lymph node metastases in locally advanced rectal
carcinoma.
AB - PURPOSE: We hypothesized that a reduction in the size of the lymph nodes after
neoadjuvant therapy for locally advanced rectal carcinoma would be associated
with decreased lymph node metastases and/or a better prognosis. METHODS: Between
March 2006 and April 2012, 71 patients with primary rectal cancer received
neoadjuvant chemoradiation therapy (CRT). For all lymph nodes 5 mm or larger in
size, the major and minor axes were measured on CT scan images, and the product
was calculated. The lymph node size was determined before and after CRT. The
patients were divided into three groups based on the lymph node size before and
after treatment. Group A exhibited a reduction in size of 60% or more, Group B a
reduction of less than 60% and Group C had no lymph node enlargement before
treatment. RESULTS: The incidence of lymph node metastases on pathological
examination was 15% in Group A and 50% in Group B (p = 0.006). The five-year
disease-free survival in Group A was 84% compared with 78% in Group B (log rank p
= 0.34). The five-year overall survival in Group A was 92% compared with 74% in
Group B (log rank p = 0.088). CONCLUSIONS: A reduction in the size of enlarged
lymph nodes after neoadjuvant therapy may be a useful prognostic factor for
recurrence and survival.
PMID- 25119167
TI - In memoriam Professor Przemyslaw Gabryel (01.12.1919 - 27.04.2014).
PMID- 25119165
TI - Brain-derived neurotrophic factor and interleukin-6 levels in the serum and
cerebrospinal fluid of children with viral infection-induced encephalopathy.
AB - We investigated changes in the brain-derived neurotrophic factor (BDNF) and
interleukin (IL)-6 levels in pediatric patients with central nervous system (CNS)
infections, particularly viral infection-induced encephalopathy. Over a 5-year
study period, 24 children hospitalized with encephalopathy were grouped based on
their acute encephalopathy type (the excitotoxicity, cytokine storm, and
metabolic error types). Children without CNS infections served as controls. In
serum and cerebrospinal fluid (CSF) samples, BDNF and IL-6 levels were increased
in all encephalopathy groups, and significant increases were noted in the
influenza-associated and cytokine storm encephalopathy groups. Children with
sequelae showed higher BDNF and IL-6 levels than those without sequelae. In
pediatric patients, changes in serum and CSF BDNF and IL-6 levels may serve as a
prognostic index of CNS infections, particularly for the diagnosis of
encephalopathy and differentiation of encephalopathy types.
PMID- 25119164
TI - The beneficial effect of chitooligosaccharides on cell behavior and function of
primary Schwann cells is accompanied by up-regulation of adhesion proteins and
neurotrophins.
AB - Chitosan-based tissue engineered nerve grafts are successfully used for bridging
peripheral nerve gaps. The biodegradation products of chitosan are water
dissolvable chitooligosaccharides (COSs), which have been shown to support
peripheral nerve regeneration. In this study, we aimed to examine in vitro
interactions between COSs and Schwann cells (SCs), the principal glial cells in
the peripheral nervous system. Treatment of primary SCs with COSs enhanced cell
survival and promoted cell proliferation in a dose-dependent manner (0.25-1.0
mg/ml), as determined by real-time cell analyzer-based assay, cell growth assay,
cell cycle analysis, and EdU incorporation. Western blot analysis and
immunocytochemistry with antibodies against MBP and MAG (two myelin-specific
markers) showed that COSs enhanced axonal myelination in a co-culture system
consisting of SCs and dorsal root ganglia (DRGs). Furthermore, we observed that
COSs enhanced the protein expression of N-cadherin and beta-catenin in primary
SCs, and also increased the release of BDNF and NGF in co-culture of SCs with
DRGs. And we also noted that knockdown of N-cadherin in primary SCs reduced COSs
induced increase in cell proliferation. Our findings suggested that beneficial
effects of COSs on cell behavior and functions of primary SCs might be
accompanied by up-regulation of adhesion proteins and neurotrophins, thus
providing a new insight into the supportive role of COSs during peripheral nerve
regeneration.
PMID- 25119168
TI - Review of renal tumors associated with Birt-Hogg-Dube syndrome with focus on
clinical and pathobiological aspects.
AB - Birt-Hogg-Dube syndrome (BHDS) is an autosomal dominant inherited disorder
characterized by clinical features of skin lesions, pulmonary lesions and renal
tumor. The gene responsible for this syndrome is located on chromosome 17p11.2
and designated as FLCN. In this article, we review renal tumors associated with
BHDS with a focus on clinical and pathobiological aspects. Renal tumors often
occur multifocally or bilaterally in the imaging analyses or gross examination.
Histological examination of renal tumors includes a variety of subtypes such as
hybrid oncocytic tumor, chromophobe renal cell carcinoma (RCC), oncocytoma, clear
cell RCC and papillary RCC. The histologic discordance in multiple tumors seems
to be characteristic of this syndrome. Oncocytosis is observed histologically in
about half of the cases. Several investigations have elucidated that folliculin
may be involved in the mammalian target of rapamycin (mTOR) pathway recently.
Renal tumors composed of clear cells may behave in an aggressive fashion.
However, renal tumors including hybrid oncocytic tumor, chromophobe RCC and
oncocytoma behave mostly in an indolent fashion.
PMID- 25119169
TI - Ductal adenocarcinoma of the pancreas usually retained SMAD4 and p53 protein
status as well as expression of epithelial-to-mesenchymal transition markers and
cell cycle regulators at the stage of liver metastasis.
AB - There are limited data on the biology of metastatic pancreatic ductal
adenocarcinoma (PDAC). The aim of the present study was to compare the expression
of immunohistochemical markers that may be involved in the development of
metastatic disease in primary PDAC and in synchronous liver metastatic tissues.
Thirty-two stains (corresponding to proteins encoded by 31 genes: SMAD4, TP53,
ACTA2, CDH1, CDKN1A, CLDN1, CLDN4, CLDN7, CTNNB1, EGFR, ERBB2, FN1, KRT19,
MAPK1/MAPK3, MAPK14, MKI67, MMP2, MMP9, MUC1 (3 antibodies), MUC5AC, MUC6, MTOR,
MYC, NES, PTGS2, RPS6, RPS6KB1, TGFB1, TGFBR1, VIM) were evaluated using tissue
microarray of 26 pairs of primary PDACs and their liver metastases. There were no
significant differences in expression levels of examined proteins between primary
and secondary lesions. In particular, metastatic PDAC retained the primary
tumour's SMAD4 protein status in all and p53 protein status in all but one case.
This surprising homogeneity also involved expression levels of markers of
epithelial-to-mesenchymal transition as well as cell cycle regulators studied. In
conclusion, the biological profiles of primary PDACs and their liver metastases
seemed to be similar. Molecular alterations of PDAC related to a set of
immunohistochemical markers examined in the present study were already present at
the stage of localized disease.
PMID- 25119170
TI - Selected immunohistochemical features of conventional renal cell carcinomas
coexpressing P53 and MDM2.
AB - Renal clear cell carcinoma (CCRCC) is an aggressive tumor for which new
prognostic factors are needed. It has been suggested that CCRCCs co-expressing
P53 and MDM2 could represent a special subgroup; therefore the aim of this study
was to explore their immunohistochemical features. The material studied consisted
of 470 cases of CCRCC. Immunohistochemistry for MDM2, P53, Ki-67, VEGF-A, VEGF-C,
VEGF-D, GLUT1, CA9, and CK 7 was performed on tissue microarrays and assessed
semi-quantitatively. On average, 6.6% or 5.3% of cases were P53+/MDM2+, depending
on the P53 antibody used. The mean percentage of Ki-67 positive cells was 0.6%
and p53-positive MDM2-positive cases showed significantly higher expression of Ki
67. The other immunohistochemical parameters studied did not differ between p53
positive MDM2-positive cases and the rest of the subtypes studied. Expression of
almost all immunohistochemical markers differed with respect to pT stage; only
for CA9 was the difference not significant. Furthermore, almost all
immunohistochemical markers studied differed with respect to differences in
grade; only for GLUT1 was the difference not significant. Our results suggest
that with the exception of Ki-67, there are no significant associations between
analyzed markers and the double P53+/MDM2+ phenotype.
PMID- 25119171
TI - Histochemical and immunohistochemical characteristics of elastofibromas.
AB - Elastofibromas are slow-growing and rare soft-tissue tumors. The etiology and
pathogenetic mechanisms are still controversial and there are only a few studies
in the literature investigating the histochemical, immunohistochemical, and
genetic features to determine the pathogenesis. We investigated the cellular
composition of lesions with a diagnosis of elastofibroma in 17 patients by using
histochemical and immunohistochemical methods. There were 17 cases with a mean
age of 53.5 years. Mean lesion diameter was 6.6 cm. The immunohistochemical
method showed vimentin and factor XIIIa positivity in all cases. Four cases had
focal myoglobin positivity in the spindle-shaped cells between the collagen
fibers. Spindle cells were positive for CD34 in 8 cases. Smooth muscle actin,
desmin, type 4 collagen and laminin were negative in all cases. The elastic
nature of the abnormal fibers was shown histoch with Verhoeff elastin staining
and aldehyde fuchsin staining in all cases. Our results have shown that the
concurrent positivity of factor XIIIa and CD34 in the cells forming the lesion
might show that the lesionoriginates from primitive dermal mesenchymal cells. In
addition, the myoglobin positivity found in some cases indicates the possibility
of a myofibroblastic origin of elastofibromas.
PMID- 25119172
TI - The influence of Th1/Th2 and CD4+ regulatory t cells of mesenteric lymph nodes on
systemic lipopolysaccharide.
AB - Our aims were to study the influence of the mesenteric lymph nodes (MLN) of rats
on systemic lipopolysaccharide and to identify the factor that affects the
intestinal endotoxin translocation. Ninety-six male Wistar rats were randomly
divided into a sham-operation group (S group) and a cecal ligation and
perforation group (CLP group). Twenty-four hours after modeling, we tested the
Th1/Th2 ratio and percentage of CD4+CD25+Foxp3+ Treg in the MLN. At the same
time, the lipopolysaccharide (LPS) in the abdominal aortic blood was detected. In
the CLP group, the Th1/Th2 ratio was obviously lower than in the S group.
Otherwise, the percentage of CD4+CD25+Foxp3+ Treg of the CLP group was
significantly higher than the S group. In the abdominal aortic blood, the LPS
level of the CLP group was also higher than in the S group. Through correlation
analysis, we found that the level of LPS was positively correlated with the
percentage of CD4+CD25+Foxp3+ Treg, and negatively correlated with the Th1/Th2
ratio. This model reveals that the immune suppression of the MLN might affect the
level of LPS in the abdominal aortic blood, which might play a certain role in
affecting the endotoxin translocation.
PMID- 25119173
TI - Parotid gland tumors in children - pre- and postoperative diagnostic
difficulties.
AB - Major salivary gland tumors are very rare in the developmental period. Confirming
tumor changes in the salivary gland requires precise diagnostic imaging involving
an ultrasonography scan, computed tomography and magnetic resonance. Needle
aspiration biopsy (NAB) of the tumor is of high importance. Excision is the basic
treatment method in cases of parotid gland tumor. The statistical data concerning
tumors favor less invasive methods, which seems logical in the population of
children. The surgical methods used in tumor treatment feature extracapsular
excision of tumor, partial parotidectomy and total parotidectomy, sometimes
followed by lymphatic node surgery. The clinical cases presented in the paper
show difficulties with pre- and postoperative histopathological diagnosis in
major salivary gland tumors in children. A core biopsy of the tumor may improve
the accuracy of preoperative diagnosis but it does not exclude the possibility of
misdiagnosis.
PMID- 25119174
TI - Expression of insulin-like growth factor receptor type 1 correlate with lymphatic
metastases in human gastric cancer.
AB - Most patients with gastric cancer are diagnosed at advanced clinical stages with
a high frequency of lymph node metastasis. It is very important to find novel
factors for the early diagnostic and prognostic evaluation of gastric cancer. It
has been shown that IGF-1R activates mitotic division and inhibits apoptosis of
cancer cells through the activation of signaling MAP/ERK and PI3K/Akt-1 pathways.
IGF-1R plays a role in cell transformation and maintenance of the phenotype in
modified cells. Moreover, an IGF-1 receptor effect influences the processes of
adhesion, migration, invasion and metastasis of tumor cells. The aim of the study
was to assess the expression of IGF-1R in gastric carcinoma in correlation with
selected anatomo-clinical parameters. The study enrolled a group of 49 patients
treated surgically for gastric cancer. 28 patients had no lymph node metastases.
The expression of the studied proteins was assessed using the immunohistochemical
method. We found that the expression of IGF-1R in gastric cancer is associated
with lymph node metastasis (p < 0.001), is correlated with worse prognosis and
high histological malignancy grade, and is an independent predictor of survival
in patients with gastric cancer (p < 0.001). IGF-1R may play an important role in
tumor growth and metastasis via the lymphatic pathway.
PMID- 25119175
TI - Polymorphism of the glutathione S-transferase P1 gene (GST-pi) in breast
carcinoma.
AB - Breast carcinoma is the most common cancer and cause of death among females
worldwide, including Jordan. The risk factors for breast carcinoma are linked to
DNA mutation and failure of DNA repair or detoxification systems. Identification
of susceptibility factors that predispose individuals to breast carcinoma if they
are exposed to particular environmental agents might give further insight into
the etiology of this malignancy. The glutathione S-transferase (GST) enzyme
family detoxifies carcinogenic compounds. Several genes that code for these
enzymes are polymorphic, with particular genotypes previously shown to confer an
increased carcinoma risk. The present study investigates GST-pi polymorphism in
100-tissue samples previously diagnosed as breast carcinoma, and in 48 non-cancer
age-matched breast tissues, using the restriction fragment length polymorphism
(RFLP) method for the polymerase chain reaction (PCR) product. Among breast
cancer cases, 58%, 40% and 2% were homozygous (Ile/Ile), heterozygous (Ile/Val)
and homozygous (Val/Val) respectively. In the control group, 58%, 37.5% and 4.2%
were homozygous (Ile/Ile), heterozygous (Ile/Val), and homozygous (Val/Val)
respectively. Our results did not support the involvement of GST-pi gene
polymorphism in susceptibility to breast carcinoma in the tested North Jordanian
female population.
PMID- 25119176
TI - Mast cell phenotype in benign and malignant tumors of the prostate.
AB - The molecular phenotypic heterogeneity of mast cells (MCs) makes them attractive
as potential therapeutic targets in anti-cancer adjuvant therapy. Mast cell
aggregations observed in tumors suggested their involvement in tumor
pathogenesis. Despite several studies using mast cell tryptase, MCs' involvement
in the progression of prostate tumors has not been demonstrated. The aim of our
study was to identify and quantify the phenotypic heterogeneity of MCs in
prostate lesions. Our study included 7 cases of normal prostate, 25 cases of
benign epithelial hyperplasia and 64 cases of prostate carcinoma. MCs were
immunohistochemically assessed using three markers: tryptase, chymase and CD117.
Two immunophenotypes of MCs were identified in benign lesions:
tryptase+/CD117+/chymase- and tryptase-/chymase+/CD117+, located in peritumoral
areas. Intratumoral MC phenotype of malignant lesions was characterized by
tryptase+/chymase+/CD117+, while in the peritumoral areas three different MCs
phenotypes were identified: tryptase+/chymase+/CD117-, tryptase+/CD117+/chymase-
and chymase+/CD117+/tryptase-. Our results suggest the correlation of chymase
positive MCs of the peritumoral areas and CD117 positive MCs of the intratumoral
areas with tumor grade.
PMID- 25119177
TI - Bilateral Sertoli cell adenoma in gonads, associated with serous cystadenoma.
AB - Complete androgen insensitivity syndrome is an extremely infrequent disease. The
patients exhibit female phenotype because of insensitivity to the androgen
receptor and may develop tumors, especially in their undescended gonads. We
report a case of bilateral Sertoli cell adenoma in gonads with unilateral serous
cystadenoma, in an elderly phenotypic woman with primary amenorrhea. We also
provide radiological and pathological studies.
PMID- 25119178
TI - Renal myxoma: an unexpected differential diagnosis.
AB - Myxomas are rare mesenchymal tumors that can appear in many anatomical locations,
although they are mainly seen in heart and skin. To date, only twelve cases of
pure renal myxomas have been reported in the literature. We describe a case of a
young Cuban woman with an asymptomatic irregular cyst lesion in her left kidney
which was eventually diagnosed as renal myxoma. We also provide radiological and
pathological studies.
PMID- 25119179
TI - Re: co-existence of intramuscular spindle cell lipoma with an intramuscular
ordinary lipoma. Report of a case.
PMID- 25119180
TI - Melanotic oncocytic metaplasia of the nasopharynx.
AB - We report a rare case of melanotic oncocytic metaplasia of the nasopharynx in a
63-year-old man, presenting as several black nodules up to several millimeters at
the nasopharynx. It is a benign mimicker of malignant melanoma.
PMID- 25119181
TI - A prospective study of biomarker-guided chemotherapy in patients with non-small
cell lung cancer.
AB - PURPOSE: To assess the therapeutic value of biomarker-guided chemotherapy in
patients with advanced non-small cell lung cancer (NSCLC). METHODS: Eighty-five
NSCLC patients at stage IIIb or IV were divided into two groups based on the
feasibility of biomarker analysis. Group A included patients with biomarker data
(n = 41); Group B were patients without biomarker results (n = 44). Tumor samples
obtained by fiberoptic bronchoscopy and computerized tomography-guided needle
biopsy were analyzed by immunohistochemistry for intratumoral level of excision
repair cross-complementing gene 1 (ERCC1), ribonucleotide reductase M1 (RRM1),
and beta-tubulin III. Chemotherapy regimens in Group A were determined according
to the status of molecular signatures, whereas a standard gemcitabine plus
cisplatin regimen was used for Group B. Tumor response, patient survival, and
adverse effects were monitored for both groups. RESULTS: The overall response
rate, defined as complete response plus partial response, was 56.1% for Group A,
significantly higher than that in Group B (31.8%; P = 0.024). The median
progression-free survival (PFS) time was 5.2 months for Group A, significantly
longer than that of Group B (4.1 months; P = 0.026). The 1-year survival rate of
Group A was 65.9%, significantly higher than that of Group B (40.9%; P = 0.021),
whereas the median overall survival times were 13.5 versus 12.5 months for Groups
A and B, respectively (P = 0.483). The adverse effects in the two groups were
essentially the same. CONCLUSIONS: Biomarker-tailored chemotherapy based on
ERCC1, RRM1, and beta-tubulin III expression showed significantly increased
response rate, median PFS time, and 1-year survival rate in patients with NSCLC.
PMID- 25119183
TI - The combination of Cl-IB-MECA with paclitaxel: a new anti-metastatic therapeutic
strategy for melanoma.
AB - PURPOSE: Metastatic melanoma is considered one of the most aggressive malignant
tumours, representing the deadliest form of skin cancer. Melanoma progression is
associated with the abrogation of normal controls that limit cell proliferation,
migration, and invasion, eventually leading to metastasis. Based on the variety
of cellular mechanisms involved in metastatic progression, we aimed to evaluate
the effect of inosine (50 MUM) and of the combination of Cl-IB-MECA (10 MUM) with
paclitaxel (10 ng/mL) on several stages of melanoma progression. METHODS:
Proliferation, migration, adhesion, invasion, and colony formation assays were
performed on human C32 and A375 metastatic melanoma cells. Levels of ERK1/2 were
also determined using an ELISA kit. Moreover, mouse aortic rings were treated
with vascular endothelial growth factor in order to assess the microvessel
sprouting (an indicator of angiogenesis) in the presence of the referred
compounds. RESULTS: We demonstrate that inosine induced, through A3 adenosine
receptor activation, proliferation, migration, adhesion, and invasion on C32 and
A375 melanoma cells, although with dissimilar importance on the two melanoma cell
lines. Inosine also increased colony formation on A375 cells. Levels of ERK1/2
were increased after inosine exposure and that increase was dependent on A3
adenosine receptor activation in both cell lines. Moreover, microvessel sprouting
stimulated by inosine was decreased by the combination of Cl-IB-MECA with
paclitaxel. CONCLUSIONS: Cl-IB-MECA combined with paclitaxel was able to impair
almost all of the referred metastatic related mechanisms induced by inosine,
making this approach a valuable tool for combinatory therapy against metastatic
melanoma.
PMID- 25119182
TI - Pharmacokinetics and pharmacogenomics of daunorubicin in children: a report from
the Children's Oncology Group.
AB - PURPOSE: We explored the impact of obesity, body composition, and genetic
polymorphisms on the pharmacokinetics (PK) of daunorubicin in children with
cancer. PATIENTS AND METHODS: Patients <=21 years receiving daunorubicin as an
infusion of any duration <24 h for any type of cancer were eligible. Plasma drug
concentrations were measured by high-performance liquid chromatography. Body
composition was measured by dual-energy X-ray absorptiometry. Obesity was defined
as a BMI >95% for age or as body fat >30%. NONMEM was used to perform PK model
fitting. The Affymetrix DMET chip was used for genotyping. The impact of genetic
polymorphisms was investigated using SNP/haplotype association analysis with
estimated individual PK parameters. RESULTS: A total of 107 subjects were
enrolled, 98 patients had PK sampling, and 50 patients underwent DNA analysis.
Population estimates for daunorubicin clearance and volume of distribution were
116 L/m(2)/h +/- 14% and 68.1 L/m(2) +/- 24%, respectively. Apparent
daunorubicinol clearance and volume of distribution were 26.8 L/m(2)/h +/- 5.6%
and 232 L/m(2) +/- 10%, respectively. No effect of body composition or obesity
was observed on PK. Forty-four genes with variant haplotypes were tested for
association with PK. FMO3-H1/H3 genotype was associated with lower daunorubicin
clearance than FMO3-H1/H1, p = 0.00829. GSTP1*B/*B genotype was also associated
with lower daunorubicin clearance compared to GSTP1*A/*A, p = 0.0347. However,
neither of these associations was significant after adjusting for multiple
testing by either Bonferroni or false discovery rate correction. CONCLUSIONS: We
did not detect an effect of body composition or obesity on daunorubicin PK. We
found suggestive associations between FMO3 and GSTP1 haplotypes with daunorubicin
PK that could potentially affect efficacy and toxicity.
PMID- 25119184
TI - Population pharmacokinetic and covariate analysis of pertuzumab, a HER2-targeted
monoclonal antibody, and evaluation of a fixed, non-weight-based dose in patients
with a variety of solid tumors.
AB - PURPOSE: To characterize the population pharmacokinetics (PK) of pertuzumab
across clinical trials in a variety of solid tumors, evaluate the potential
impact of patient characteristics on PK, and confirm the appropriateness of the
fixed (non-weight-based) dose. METHODS: Pertuzumab concentration data collected
following intravenous administration during eleven phase I/II studies and the
pivotal phase III trial CLEOPATRA were analyzed using nonlinear mixed-effects
modeling. The potential impact of patient and laboratory characteristics and HER2
target-related variables on pertuzumab PK were investigated in a covariate
analysis. The final model was used to confirm selection of fixed, non-weight
based dosing of pertuzumab, and to compare pertuzumab PK in CLEOPATRA with the
other studies. RESULTS: The analysis included 4,525 serum concentration
measurements from 481 patients with solid tumors. Pertuzumab PK in the 2-25 mg/kg
dose range was described by a two-compartment linear model with first-order
elimination. The elimination clearance and central compartment volume were 0.235
L/day, and 3.11 L, respectively, and the terminal elimination half-life was 18.0
days. Baseline serum albumin and lean body weight had statistically significant
effects on pertuzumab clearance; however, simulations showed that the magnitude
of their effects on pertuzumab exposure was minimal compared with overall
variability and was not clinically relevant. Thus, variations in these factors do
not require dose adjustments. CONCLUSIONS: The fixed, non-weight-based dosing of
pertuzumab, 840 mg loading dose followed by a 420 mg maintenance dose every 3
weeks, in patients with the solid tumors in this analysis is well supported by
the population pharmacokinetic modeling and simulation results.
PMID- 25119186
TI - Evolution of treatment regimens in multiple myeloma: a social network analysis.
AB - BACKGROUND: Randomized controlled trials (RCTs) are considered the gold standard
for assessing the efficacy of new treatments compared to standard treatments.
However, the reasoning behind treatment selection in RCTs is often unclear. Here,
we focus on a cohort of RCTs in multiple myeloma (MM) to understand the patterns
of competing treatment selections. METHODS: We used social network analysis (SNA)
to study relationships between treatment regimens in MM RCTs and to examine the
topology of RCT treatment networks. All trials considering induction or
autologous stem cell transplant among patients with MM were eligible for our
analysis. Medline and abstracts from the annual proceedings of the American
Society of Hematology and American Society for Clinical Oncology, as well as all
references from relevant publications were searched. We extracted data on
treatment regimens, year of publication, funding type, and number of patients
enrolled. The SNA metrics used are related to node and network level centrality
and to node positioning characterization. RESULTS: 135 RCTs enrolling a total of
36,869 patients were included. The density of the RCT network was low indicating
little cohesion among treatments. Network Betweenness was also low signifying
that the network does not facilitate exchange of information. The maximum
geodesic distance was equal to 4, indicating that all connected treatments could
reach each other in four "steps" within the same pathway of development. The
distance between many important treatment regimens was greater than 1, indicating
that no RCTs have compared these regimens. CONCLUSION: Our findings show that
research programs in myeloma, which is a relatively small field, are surprisingly
decentralized with a lack of connectivity among various research pathways. As a
result there is much crucial research left unexplored. Using SNA to visually and
analytically examine treatment networks prior to designing a clinical trial can
lead to better designed studies.
PMID- 25119185
TI - Multiplexing spheroid volume, resazurin and acid phosphatase viability assays for
high-throughput screening of tumour spheroids and stem cell neurospheres.
AB - Three-dimensional cell culture has many advantages over monolayer cultures, and
spheroids have been hailed as the best current representation of small avascular
tumours in vitro. However their adoption in regular screening programs has been
hindered by uneven culture growth, poor reproducibility and lack of high
throughput analysis methods for 3D. The objective of this study was to develop a
method for a quick and reliable anticancer drug screen in 3D for tumour and human
foetal brain tissue in order to investigate drug effectiveness and selective
cytotoxic effects. Commercially available ultra-low attachment 96-well round
bottom plates were employed to culture spheroids in a rapid, reproducible manner
amenable to automation. A set of three mechanistically different methods for
spheroid health assessment (Spheroid volume, metabolic activity and acid
phosphatase enzyme activity) were validated against cell numbers in healthy and
drug-treated spheroids. An automated open-source ImageJ macro was developed to
enable high-throughput volume measurements. Although spheroid volume
determination was superior to the other assays, multiplexing it with resazurin
reduction and phosphatase activity produced a richer picture of spheroid
condition. The ability to distinguish between effects on malignant and the
proliferating component of normal brain was tested using etoposide on UW228-3
medulloblastoma cell line and human neural stem cells. At levels below 10 uM
etoposide exhibited higher toxicity towards proliferating stem cells, whereas at
concentrations above 10 uM the tumour spheroids were affected to a greater
extent. The high-throughput assay procedures use ready-made plates, open-source
software and are compatible with standard plate readers, therefore offering high
predictive power with substantial savings in time and money.
PMID- 25119187
TI - Use of Kampo diagnosis in randomized controlled trials of Kampo products in
Japan: a systematic review.
AB - BACKGROUND: The Committee for Evidence-based Medicine (EBM) of the Japan Society
for Oriental Medicine started compiling Evidence Reports of Kampo Treatment
(EKAT) in 2007. EKAT is a compilation of structured abstracts of randomized
controlled trials (RCTs), along with comments by a third party reviewer. As of 31
December, 2012, there were 378 RCTs of Kampo medicines in Japan. The primary
research question of this study is "How frequently is Kampo diagnosis used in
RCTs of Kampo medicines?" The secondary research question is "When is Kampo
diagnosis used in RCTs?" MATERIALS AND METHODS: The structured abstract (SA) of
each RCT article was reviewed to examine how Kampo diagnosis was used in RCTs,
especially how Kampo diagnosis was used in the randomization process. RESULTS:
Kampo diagnosis was used before randomization in 27 RCTs (7.1%), after
randomization in 31 RCTs (8.2%), and not used in 320 RCTs (84.7%). Before
randomization, Kampo diagnosis was used as a criterion for inclusion in 10 RCTs,
criterion for exclusion in 9 RCTs, and criteria for both inclusion and exclusion
in 2 RCTs. Kampo formulas were determined according to Kampo diagnosis in 7 RCTs.
After randomization, subgroup analyses according to Kampo diagnosis were done in
27 RCTs, and grade of disease severity at Kampo diagnosis was used for analysis
as an endpoint in 4 RCTs. CONCLUSIONS: Kampo diagnosis was used before
randomization only in approximately 15% of RCTs, and the number of RCT articles
using Kampo diagnosis after randomization was almost the same as that before
randomization. Further studies to determine the good RCTs conforming to CONSORT
requirements and good systematic reviews conforming to PRISMA requirements are
needed to clarify the significance of Kampo diagnosis.
PMID- 25119188
TI - Suberoylanilide hydroxamic acid induces ROS-mediated cleavage of HSP90 in
leukemia cells.
AB - Heat shock protein 90 (HSP90) is a molecular chaperone that supports stability of
client proteins. We found that HSP90 was cleaved to 55 kDa protein after
treatment with histone deacetylase (HDAC) inhibitors including suberoylanilide
hydroxamic acid (SAHA) in several leukemia cell lines. We further analyzed
molecular changes induced by SAHA in K562 cells. The SAHA-induced cleavage of
HSP90 was blocked by a pan-caspase inhibitor, z-VAD-fmk, implying that the
process is dependent on caspase activity. However, the experiments using
antagonistic and agonistic Fas antibodies revealed that the cleavage of HSP90 was
not dependent on Fas signaling. SAHA induced generation of reactive oxygen
species (ROS), and the cleavage of HSP90 was blocked by a ROS scavenger N
acetylcystein (NAC). We also confirmed that hydrogen peroxide (H2O2) induced
cleavage of HSP90 in a similar manner. Caspase 2, 3, 4, 6, 8, and 10 were
activated by treatment with SAHA, and the activities were reduced by the
pretreatment of NAC. Treatment of the cells with caspase 10 inhihitor, but not
other inhibitors of caspases activated by SAHA, prevented cleavage of HSP90 by
SAHA. SAHA-induced ROS generation and HSP90 cleavage were dependent on newly
synthesized unknown proteins. Taken together, our results suggest that the
cleavage of HSP90 by SAHA is mediated by ROS generation and caspase 10
activation. HSP90 cleavage may provide an additional mechanism involved in anti
cancer effects of HDAC inhibitors.
PMID- 25119189
TI - Movement coordination during conversation.
AB - Behavioral coordination and synchrony contribute to a common biological mechanism
that maintains communication, cooperation and bonding within many social species,
such as primates and birds. Similarly, human language and social systems may also
be attuned to coordination to facilitate communication and the formation of
relationships. Gross similarities in movement patterns and convergence in the
acoustic properties of speech have already been demonstrated between interacting
individuals. In the present studies, we investigated how coordinated movements
contribute to observers' perception of affiliation (friends vs. strangers)
between two conversing individuals. We used novel computational methods to
quantify motor coordination and demonstrated that individuals familiar with each
other coordinated their movements more frequently. Observers used coordination to
judge affiliation between conversing pairs but only when the perceptual stimuli
were restricted to head and face regions. These results suggest that observed
movement coordination in humans might contribute to perceptual decisions based on
availability of information to perceivers.
PMID- 25119191
TI - Understanding reproducibility of human IVF traits to predict next IVF cycle
outcome.
AB - PURPOSE: Evaluating the failed IVF cycle often provides useful prognostic
information. Before undergoing another attempt, patients experiencing an
unsuccessful IVF cycle frequently request information about the probability of
future success. Here, we introduced the concept of reproducibility and formulae
to predict the next IVF cycle outcome. METHODS: The experimental design was based
on the retrospective review of IVF cycle data from 2006 to 2013 in two different
IVF centers and statistical analysis. The reproducibility coefficients (r) of IVF
traits including number of oocytes retrieved, oocyte maturity, fertilization,
embryo quality and pregnancy were estimated using the interclass correlation
coefficient between the repeated IVF cycle measurements for the same patient by
variance component analysis. The formulae were designed to predict next IVF cycle
outcome. RESULTS: The number of oocytes retrieved from patients and their
fertilization rate had the highest reproducibility coefficients (r = 0.81 ~
0.84), which indicated a very close correlation between the first retrieval cycle
and subsequent IVF cycles. Oocyte maturity and number of top quality embryos had
middle level reproducibility (r = 0.38 ~ 0.76) and pregnancy rate had a relative
lower reproducibility (r = 0.23 ~ 0.27). Based on these parameters, the next
outcome for these IVF traits might be accurately predicted by the designed
formulae. CONCLUSIONS: The introduction of the concept of reproducibility to our
human IVF program allows us to predict future IVF cycle outcomes. The traits of
oocyte numbers retrieved, oocyte maturity, fertilization, and top quality embryos
had higher or middle reproducibility, which provides a basis for accurate
prediction of future IVF outcomes. Based on this prediction, physicians may
counsel their patients or change patient's stimulation plans, and laboratory
embryologists may improve their IVF techniques accordingly.
PMID- 25119190
TI - Resolving fluorophores by unmixing multispectral fluorescence tomography with
independent component analysis.
AB - It is a challenging problem to resolve and identify drug (or non-specific
fluorophore) distribution throughout the whole body of small animals in vivo. In
this article, an algorithm of unmixing multispectral fluorescence tomography
(MFT) images based on independent component analysis (ICA) is proposed to solve
this problem. ICA is used to unmix the data matrix assembled by the
reconstruction results from MFT. Then the independent components (ICs) that
represent spatial structures and the corresponding spectrum courses (SCs) which
are associated with spectral variations can be obtained. By combining the ICs
with SCs, the recovered MFT images can be generated and fluorophore concentration
can be calculated. Simulation studies, phantom experiments and animal experiments
with different concentration contrasts and spectrum combinations are performed to
test the performance of the proposed algorithm. Results demonstrate that the
proposed algorithm can not only provide the spatial information of fluorophores,
but also recover the actual reconstruction of MFT images.
PMID- 25119192
TI - Anti-mullerian hormone as a diagnostic and prognostic tool for PCOS patients.
AB - PURPOSE: To determine whether the measurement of serum AMH can be used to
diagnose PCOS and as a tool to predict the prognosis of PCOS. METHODS: This is a
case-control study. Women of reproductive age (18-35 years) were recruited
consecutively at a tertiary academic hospital during the period of March 2009
October 2011 and were divided into case (PCOS patients defined by the Rotterdam
criteria) and control groups (non-PCOS patients). Menstrual history, clinical
manifestations of hyperandrogenism, ovarian ultrasound assessments, and the
levels of AMH, LH, FSH, and estradiol were collected. RESULTS: Seventy-one cases
and 71 controls were recruited. AMH serum levels were significantly higher in
PCOS patients than in controls. The Area Under the Curve (AUC) of the serum AMH
assay in PCOS patients reached a value of 0.870. With a cut-off value of 4.45
ng/ml, the serum AMH level had a sensitivity of 76.1 % and a specificity of 74.6
%. The most common phenotypes of PCOS in this study were anovulation and
polycystic ovary (63.4 %). However, the mean level of AMH was highest in the
phenotypes of anovulation, polycystic ovaries and hyperandrogenism (11.1 ng/ml).
CONCLUSIONS: In Indonesian women, AMH can be used as an alternative diagnostic
criteria for PCOS patients with a cut-off value of 4.45 ng/ml. AMH value rise
when hyperandrogenism is present therefore serum AMH levels also reflect the
phenotype of PCOS. However, these findings must be confirmed with larger clinical
studies.
PMID- 25119193
TI - Response of red deer stags (Cervus elaphus) to playback of harsh versus common
roars.
AB - Red deer stags (Cervus elaphus) give two distinct types of roars during the
breeding season, the "common roar" and the "harsh roar." Harsh roars are more
frequent during contexts of intense competition, and characterized by a set of
features that increase their perceptual salience, suggesting that they signal
heightened arousal. While common roars have been shown to encode size information
and mediate both male competition and female choice, to our knowledge, the
specific function of harsh roars during male competition has not yet been
studied. Here, we investigate the hypothesis that the specific structure of male
harsh roars signals high arousal to competitors. We contrast the behavioral
responses of free ranging, harem-holding stags to the playback of harsh roars
from an unfamiliar competitor with their response to the playback of common roars
from the same animal. We show that males react less strongly to sequences of
harsh roars than to sequences of common roars, possibly because they are
reluctant to escalate conflicts with highly motivated and threatening unfamiliar
males in the absence of visual information. While future work should investigate
the response of stags to harsh roars from familiar opponents, our observations
remain consistent with the hypothesis that harsh roars may signal motivation
during male competition, and illustrate how intrasexual selection can contribute
to the diversification of male vocal signals.
PMID- 25119194
TI - Optimal duration of anticoagulation. Provoked versus unprovoked VTE and role of
adjunctive thrombophilia and imaging tests.
AB - Once anticoagulation is stopped, the risk of recurrent venous thromboembolism
(VTE) over years after a first episode is consistently around 30%. This risk is
higher in patients with unprovoked than in those with (transient) provoked VTE,
and among the latter in patients with medical than in those with surgical risk
factors. Baseline parameters that have been found to be related to the risk of
recurrent VTE are the proximal location of deep-vein thrombosis, obesity, old
age, male sex and non-0 blood group, whereas the role of inherited thrombophilia
is controversial. The persistence of residual vein thrombosis at ultrasound
assessment has consistently been shown to increase the risk, as do persistently
high values of D-dimer and the early development of the post-thrombotic syndrome.
Although the latest international guidelines suggest indefinite anticoagulation
for most patients with the first episode of unprovoked VTE, strategies that
incorporate the assessment of residual vein thrombosis and D-dimer have the
potential to identify subjects in whom anticoagulation can be safely
discontinued. Moreover, new opportunities are offered by a few emerging anti-Xa
and anti-IIa oral compounds, which are likely to induce fewer haemorrhagic
complications than vitamin K antagonists while preserving the same effectiveness;
and by low-dose aspirin, which has the potential to prevent the occurrence of
both venous and arterial thrombotic events.
PMID- 25119203
TI - Save the children.
PMID- 25119202
TI - Modeling the inflammatory response in the hypothalamus ensuing heat stroke:
iterative cycle of model calibration, identifiability analysis, experimental
design and data collection.
AB - Heat Stroke (HS) is a life-threatening illness caused by prolonged exposure to
heat that causes severe hyperthermia and nervous system abnormalities. The long
term consequences of HS are poorly understood and deeper insight is required to
find possible treatment strategies. Elevated pro- and anti-inflammatory cytokines
during HS recovery suggest to play a major role in the immune response. In this
study, we developed a mathematical model to understand the interactions and
dynamics of cytokines in the hypothalamus, the main thermoregulatory center in
the brain. Uncertainty and identifiability analysis of the calibrated model
parameters revealed non-identifiable parameters due to the limited amount of
data. To overcome the lack of identifiability of the parameters, an iterative
cycle of optimal experimental design, data collection, re-calibration and model
reduction was applied and further informative experiments were suggested.
Additionally, a new method of approximating the prior distribution of the
parameters for Bayesian optimal experimental design based on the profile
likelihood is presented.
PMID- 25119201
TI - Bone mineral density and vitamin D status in ambulatory and non-ambulatory
children with cerebral palsy.
AB - This study assessed distal femur and lumbar spine bone mineral density (BMD) Z
scores in children with cerebral palsy. BMD z-score was lower in non-ambulatory
than in ambulatory children. Somewhat surprisingly, among ambulatory children,
those with better walking abilities had higher BMD z-score than those with more
impaired walking ability. INTRODUCTION: Children with cerebral palsy (CP) have
increased risk for low bone mineral density (BMD). The aim was to explore the
difference in BMD at the distal femur and lumbar spine between ambulatory and non
ambulatory children with CP and the relationship between vitamin D status and
BMD. METHODS: Fifty-one children (age range 8-18 years; 20 girls) with CP
participated. Their BMD Z-scores were measured in the lumbar spine and the distal
femur using dual X-ray absorptiometry, and 25-hydroxy-vitamin D (25-OHD)
concentrations were measured in serum. Children with GMFCS level I-III were
defined as 'walkers' while children with level IV-V were defined as 'non-walkers.
RESULTS: Non-walkers had lower mean BMD Z-scores (range -1.7 to -5.4) than
walkers at all sites (range -0.8 to -1.5). Among walkers, BMD Z-scores at the
distal femur were lower in those with GMFCS level II than with level I (p values
< 0.004). A similar difference was found between the affected and unaffected limb
in children with hemiplegia. Mean 25-OHD concentration was 45 nmol/L (SD = 18);
lower in walkers (mean = 41 nmol/L; SD = 18) than in non-walkers (mean = 53
nmol/L; SD = 19; p = 0.041). There were no correlations between 25-OHD and BMD z
scores. CONCLUSIONS: The main predictor of low BMD Z-scores in the distal femur
was the inability to walk, but the results suggest that the degree of the
neuromotor impairment may also be a significant predictor. Vitamin D status did
not correlate with BMD z-scores.
PMID- 25119204
TI - Future computing.
PMID- 25119217
TI - Native ecosystems blitzed by drought.
PMID- 25119205
TI - China should aim for a total cap on emissions.
PMID- 25119218
TI - Health check for deep-sea mining.
PMID- 25119219
TI - Teen drug use gets supersize study.
PMID- 25119220
TI - US assesses virus of the Caribbean.
PMID- 25119221
TI - Online collaboration: Scientists and the social network.
PMID- 25119222
TI - Society: Don't blame the mothers.
PMID- 25119225
TI - Conservation: White possums must stay cool to survive.
PMID- 25119226
TI - Centenary: Russian stamp to honour physicist.
PMID- 25119227
TI - Transgenic crops: Mexican GM maize rift is not so simple.
PMID- 25119228
TI - Sexual harassment: Create ethics codes to curb sex abuse.
PMID- 25119229
TI - Neuroscience: What females really want.
PMID- 25119230
TI - Solar system: Sandcastles in space.
PMID- 25119231
TI - Condensed-matter physics: Glasses made from pure metals.
PMID- 25119232
TI - Astronomical instrumentation: Atmospheric blurring has a new enemy.
PMID- 25119233
TI - Limits on fundamental limits to computation.
AB - An indispensable part of our personal and working lives, computing has also
become essential to industries and governments. Steady improvements in computer
hardware have been supported by periodic doubling of transistor densities in
integrated circuits over the past fifty years. Such Moore scaling now requires
ever-increasing efforts, stimulating research in alternative hardware and
stirring controversy. To help evaluate emerging technologies and increase our
understanding of integrated-circuit scaling, here I review fundamental limits to
computation in the areas of manufacturing, energy, physical space, design and
verification effort, and algorithms. To outline what is achievable in principle
and in practice, I recapitulate how some limits were circumvented, and compare
loose and tight limits. Engineering difficulties encountered by emerging
technologies may indicate yet unknown limits.
PMID- 25119234
TI - Cohesive forces prevent the rotational breakup of rubble-pile asteroid (29075)
1950 DA.
AB - Space missions and ground-based observations have shown that some asteroids are
loose collections of rubble rather than solid bodies. The physical behaviour of
such 'rubble-pile' asteroids has been traditionally described using only
gravitational and frictional forces within a granular material. Cohesive forces
in the form of small van der Waals forces between constituent grains have
recently been predicted to be important for small rubble piles (ten kilometres
across or less), and could potentially explain fast rotation rates in the small
asteroid population. The strongest evidence so far has come from an analysis of
the rotational breakup of the main-belt comet P/2013 R3 (ref. 7), although that
was indirect and poorly constrained by observations. Here we report that the
kilometre-sized asteroid (29075) 1950 DA (ref. 8) is a rubble pile that is
rotating faster than is allowed by gravity and friction. We find that cohesive
forces are required to prevent surface mass shedding and structural failure, and
that the strengths of the forces are comparable to, though somewhat less than,
the forces found between the grains of lunar regolith.
PMID- 25119235
TI - Formation of monatomic metallic glasses through ultrafast liquid quenching.
AB - It has long been conjectured that any metallic liquid can be vitrified into a
glassy state provided that the cooling rate is sufficiently high. Experimentally,
however, vitrification of single-element metallic liquids is notoriously
difficult. True laboratory demonstration of the formation of monatomic metallic
glass has been lacking. Here we report an experimental approach to the
vitrification of monatomic metallic liquids by achieving an unprecedentedly high
liquid-quenching rate of 10(14) K s(-1). Under such a high cooling rate, melts of
pure refractory body-centred cubic (bcc) metals, such as liquid tantalum and
vanadium, are successfully vitrified to form metallic glasses suitable for
property interrogations. Combining in situ transmission electron microscopy
observation and atoms-to-continuum modelling, we investigated the formation
condition and thermal stability of the monatomic metallic glasses as obtained.
The availability of monatomic metallic glasses, being the simplest glass formers,
offers unique possibilities for studying the structure and property relationships
of glasses. Our technique also shows great control over the reversible
vitrification-crystallization processes, suggesting its potential in micro
electromechanical applications. The ultrahigh cooling rate, approaching the
highest liquid-quenching rate attainable in the experiment, makes it possible to
explore the fast kinetics and structural behaviour of supercooled metallic
liquids within the nanosecond to picosecond regimes.
PMID- 25119238
TI - Developing a genetic fuzzy system for risk assessment of mortality after cardiac
surgery.
AB - Cardiac events could be taken into account as the leading causes of death
throughout the globe. Such events also trigger an undesirable increase in what
treatment procedures cost. Despite the giant leaps in technological development
in heart surgery, coronary surgery still carries the high risk of the mortality.
Besides, there is still a long way ahead to accurately predict and assess the
mortality risk. This study is an attempt to develop an expert system for the risk
assessment of mortality following the cardiac surgery. The developed system
involves three main steps. In the first step, a filtering feature selection
method is applied to select the best features. In the second step, an ad hoc data
driven method is utilized to generate the preliminary fuzzy inference system.
Finally, a hybrid optimization method is presented to select the optimum subset
of the rules. The study relies on 1,811 samples to evaluate the diagnosis
performance of the proposed system. The obtained classification accuracy is very
promising with regard to other benchmark classification methods including binary
logistic regression (LR) and multilayer perceptron neural network (MLP) with the
same attributes. The developed system leads to 100% sensitivity and 84.7%
specificity, while LR and MLP methods statistically come up with lower figures
(65, 78.6 and 65%, 75.8%), respectively. Now, a fuzzy supportive tool can be
potentially taken as an alternative for the current mortality risk assessment
system that are applied in coronary surgeries, and are chiefly based on crisp
database.
PMID- 25119237
TI - Transport networks and inequities in vaccination: remoteness shapes measles
vaccine coverage and prospects for elimination across Africa.
AB - Measles vaccination is estimated to have averted 13.8 million deaths between 2000
and 2012. Persisting heterogeneity in coverage is a major contributor to
continued measles mortality, and a barrier to measles elimination and
introduction of rubella-containing vaccine. Our objective is to identify
determinants of inequities in coverage, and how vaccine delivery must change to
achieve elimination goals, which is a focus of the WHO Decade of Vaccines. We
combined estimates of travel time to the nearest urban centre (?50 000 people)
with vaccination data from Demographic Health Surveys to assess how remoteness
affects coverage in 26 African countries. Building on a statistical mapping of
coverage against age and geographical isolation, we quantified how modifying the
rate and age range of vaccine delivery affects national coverage. Our scenario
analysis considers increasing the rate of delivery of routine vaccination,
increasing the target age range of routine vaccination, and enhanced delivery to
remote areas. Geographical isolation plays a key role in defining vaccine
inequity, with greater inequity in countries with lower measles vaccine coverage.
Eliminating geographical inequities alone will not achieve thresholds for herd
immunity, indicating that changes in delivery rate or age range of routine
vaccination will be required. Measles vaccine coverage remains far below targets
for herd immunity in many countries on the African continent and is likely to be
inadequate for achieving rubella elimination. The impact of strategies such as
increasing the upper age range eligible for routine vaccination should be
considered.
PMID- 25119239
TI - Construction the model on the breast cancer survival analysis use support vector
machine, logistic regression and decision tree.
AB - The aim of the paper is to use data mining technology to establish a
classification of breast cancer survival patterns, and offers a treatment
decision-making reference for the survival ability of women diagnosed with breast
cancer in Taiwan. We studied patients with breast cancer in a specific hospital
in Central Taiwan to obtain 1,340 data sets. We employed a support vector
machine, logistic regression, and a C5.0 decision tree to construct a
classification model of breast cancer patients' survival rates, and used a 10
fold cross-validation approach to identify the model. The results show that the
establishment of classification tools for the classification of the models
yielded an average accuracy rate of more than 90% for both; the SVM provided the
best method for constructing the three categories of the classification system
for the survival mode. The results of the experiment show that the three methods
used to create the classification system, established a high accuracy rate,
predicted a more accurate survival ability of women diagnosed with breast cancer,
and could be used as a reference when creating a medical decision-making frame.
PMID- 25119240
TI - Analysis of laryngeal fractures in decomposed bodies using microfocus computed
tomography (mfCT).
AB - Postmortem computed tomography (CT) is now routinely performed in forensic
autopsies. Microfocus computed tomography (mfCT) has attracted recent attention
because it can provide more detailed information than routine postmortem CT can.
This feasibility study evaluated the usefulness of mfCT for examination of the
hyoid bone and thyroid cartilage in cases of suspected strangulation, where
advanced decomposition precludes detection of petechial hemorrhages and
hemorrhages adjacent to fractures. The results show that mfCT was useful for
identification of thin fracture lines in the fragile laryngeal structures. We
suggest that mfCT should be considered for forensic autopsies in cases of
suspected strangulation with advanced decomposition.
PMID- 25119241
TI - High variation in hypoxanthine determination after analytical treatment of
vitreous humor samples.
AB - In the field of legal medicine the correct determination of the time of death is
of great importance because an error in calculating the post-mortem interval
(PMI) could be crucial in a criminal investigation. The quantification of
hypoxanthine (Hx) concentration in the vitreous humor (VH) as a means to estimate
PMI is useful when dealing with a recent time interval of death and has several
advantages over other biological matrices. However, due to its viscous nature, VH
has to be liquefied prior to its analysis, and the different procedures to
liquefy it may cause alterations in Hx concentration, and hence in estimation of
PMI. The aim of this study was to determine differences in Hx concentration after
applying several pre-analytical treatments to different aliquots of the same VH
sample. Enzymatic digestion, sonication, centrifugation and heat were the
liquefying methods applied to reduce the viscosity of 105 VH samples. Analysis
was performed using solid phase extraction and liquid chromatography in tandem
with mass spectrometry. Statistically significant differences in the measured Hx
concentrations were found between enzymatic digestion and the other three methods
analyzed (sonication, centrifugation, and heat). Additionally, high data
dispersion was found under heat treatment but was not observed for centrifugation
or sonication, where similar and more moderate results were found. We conclude
that high variations in Hx determination are observed when enzymatic digestion or
heat treatment is used and we therefore recommend sonication or centrifugation to
quantify Hx concentration in the VH.
PMID- 25119242
TI - Is cerebral swelling following cranio-cerebral trauma instantaneous? An insight
into the Byard and Vink proposition.
PMID- 25119244
TI - Forensic text books: how to publish and perish, all at the same time.
PMID- 25119243
TI - Is the phenomenon of "crow's feet" in cases of high-voltage accidents a vital
reaction?
PMID- 25119245
TI - Improvement of Aspergillus oryzae NRRL 3484 by mutagenesis and optimization of
culture conditions in solid-state fermentation for the hyper-production of
extracellular cellulase.
AB - Spore suspensions of Aspergillus oryzae NRRL 3484 were subjected to mutagenesis
using ultraviolet-irradiation followed by chemical treatments to improve the
biosynthesis of cellulase. Ten mutant strains namely UEAC7, UEAR5, UNAC4, UNAC16,
UNAR19, UNBC7, UNBR3, UNBR10, UNBR23 and UNBR25 were selected and their
extracellular cellulase activities were assayed. Mutant UNAC4 gave the highest
cellulase production [2,455 +/- 28 U/g-dry substrate (ds) for filter paper-ase
(FP-ase)] in a yield 4-fold exceeding that of the wild type strain (578 +/- 5.0
U/g-ds for FP-ase). Rice straw (RS) was used as a sole carbon source for the
enzyme production at a concentration of 10 % (w/v). Maximum cellulase production
was achieved at initial medium pH 5.5, initial moisture content 77 % and an
incubation temperature 28 degrees C on the fifth day of growth. NH4Cl proved to
be the suitable added nitrogen source for maximum enzyme production followed by
peptone. These results clearly indicate the cost-effectiveness of solid state
fermentation technology in the economic production of extracellular cellulase.
The hyper-production of cellulase by mutant strain UNAC4 has potential for
industrial processes that convert lignocellulosic material (e.g. RS) into
products of commercial value such as glucose and biofuels.
PMID- 25119246
TI - Soil bacterial diversity in degraded and restored lands of Northeast Brazil.
AB - Land degradation deteriorates biological productivity and affects environmental,
social, and economic sustainability, particularly so in the semi-arid region of
Northeast Brazil. Although some studies exist reporting gross measures of soil
microbial parameters and processes, limited information is available on how land
degradation and restoration strategies influence the diversity and composition of
soil microbial communities. In this study we compare the structure and diversity
of bacterial communities in degraded and restored lands in Northeast Brazil and
determine the soil biological and chemical properties influencing bacterial
communities. We found that land degradation decreased the diversity of soil
bacteria as indicated by both reduced operational taxonomic unit (OTU) richness
and Shannon index. Soils under native vegetation and restoration had
significantly higher bacterial richness and diversity than degraded soils.
Redundancy analysis revealed that low soil bacterial diversity correlated with a
high respiratory quotient, indicating stressed microbial communities. By
contrast, soil bacterial communities in restored land positively correlated with
high soil P levels. Importantly, however, we found significant differences in the
soil bacterial community composition under native vegetation and in restored
land, which may indicate differences in their functioning despite equal levels of
bacterial diversity.
PMID- 25119247
TI - Low expression of microRNA-30c promotes invasion by inducing epithelial
mesenchymal transition in non-small cell lung cancer.
AB - MicroRNA (miR)-30c has been identified as a tumor suppressor gene in numerous
diseases. Aberrant miR-30c expression has been associated with the invasion of
different types of cancer. However, the potential mechanisms underlying the
association between miR-30c and invasion has been poorly elucidated in non-small
cell lung cancer (NSCLC). In the present study, quantitative polymerase chain
reaction demonstrated that the expression of miR-30c was reduced in lung cancer
specimens (n=85). Suppressing the expression of miR-30c promoted the invasion of
A549 cells, while overexpressed miR-30c inhibited the invasion of A549 cells.
Furthermore, aberrant miR-30c expression was able to control the expression
levels of markers (E-cadherin, snail and vimentin) of epithelial mesenchymal
transition (EMT). In conclusion, miR-30c regulated the invasion of NSCLC cells
and low miR-30 levels induced EMT.
PMID- 25119248
TI - [Regulating the internet: a comparative analysis of Brazil, Chile, Spain, the US,
and France].
AB - Global governance is of key concern in the current debate over the workings of
the world's computer network, and Brazil has played a notable role in this
process, especially after approval of the Marco Civil da Internet (law 12.965,
april 23, 2014), which defines Brazil's regulatory framework for the internet.
Dubbed the internet bill of rights, this law sets out the principles, guarantees,
rights, and duties of internet users and providers in Brazil. Based on the
fundamental categories of net neutrality, internet users' right to privacy, and
copyright discussions from the perspective of intellectual property, the article
offers a comparative analysis of regulations in five countries: Brazil, Chile,
Spain, the US, and France.
PMID- 25119249
TI - [Obsessions before Freud: history and clinical practice].
AB - The article analyses the significance of the concept of "obsession" in nineteenth
century alienism. From a clinical point of view, Esquirol's description was
completed by other authors (Jules Falret, Legrand du Saulle). In the area of
psychopathological studies, French alienism, with Morel's emotional delirium or
Janet's psychasthenia, defended the emotional theory, as opposed to the
intellectual disorder proposed by German doctors. Lastly, the importance of the
cultural framework is stressed in the appearance of obsessive symptoms and their
interpretation. Along these lines, the article discusses the relationship of
religious scruples to melancholy or the appearance of diagnostic categories
subject to fin de siecle codes and mentalities.
PMID- 25119252
TI - Statistics commentary series: commentary #4--relative risk and the number needed
to treat.
PMID- 25119251
TI - Rifampicin improves neuronal apoptosis in LPS-stimulated co-cultured BV2 cells
through inhibition of the TLR-4 pathway.
AB - Agents inhibiting microglial activation are attracting attention as candidate
drugs for neuroprotection in neurodegenerative diseases. Recently, researchers
have focused on the immunosuppression induced by rifampicin. Our previous study
showed that rifampicin inhibits the production of lipopolysaccharide (LPS)
induced pro-inflammatory mediators and improves neuron survival in inflammation;
however, the mechanism through which rifampicin inhibits microglial inflammation
and its neuroprotective effects are not completely understood. In this study, we
examined the effects of rifampicin on morphological changes induced by LPS in
murine microglial BV2 cells. Then we investigated, in BV2 microglia, the effects
of rifampicin on two signaling pathway componentss stimulated by LPS, the Toll
like receptor-4 (TLR-4) and the nuclear factor-kappaB (NF-kappaB). In addition,
we co-cultured BV2 microglia and neurons to observe the indirect neuroprotective
effects of rifampicin. Rifampicin inhibited LPS-stimulated expression of the TLR
4 gene. When neurons were co-cultured with LPS-stimulated BV2 microglia, pre
treatment with rifampicin increased neuronal viability and reduced the number of
apoptotic cells. Taken together, these findings suggest that rifampicin, with its
anti-inflammatory properties, may be a promising agent for the treatment of
neurodegenerative diseases.
PMID- 25119250
TI - The toxicology investigators consortium case registry-the 2013 experience.
AB - The Toxicology Investigators Consortium (ToxIC) Case Registry was established in
2010 by the American College of Medical Toxicology. The Registry includes all
medical toxicology consultations performed at participating sites. This report
summarizes the Registry data for 2013. A query of the ToxIC Registry was carried
out for the dates of January 1 through December 31, 2013. Specific data reviewed
for analysis included demographics (age, gender), source of consultation, reasons
for consultation, agents involved in toxicological exposures, signs, symptoms and
clinical findings, and treatment. A total of 8,598 cases were entered into the
Registry in 2013. Females accounted for 49.2 % of cases, males for 47.7 %, and
gender was not reported in 3.1 %. The majority of patients (63.4 %) were adults
between the ages of 19 and 65 years. There were 93 fatalities (1.1 %). Most
referrals for medical toxicology consultation originated from the emergency
department (59.7 %) or inpatient services (16.7 %). Exposures to pharmaceutical
products (intentional and unintentional) made up 50.0 % of cases. Illicit drug
abuse (8.0 %) and adverse drug reactions (ADRs) (4.8 %) were the next most
frequent reasons for consultation. Similar to past years, nonopioid analgesics,
sedative-hypnotics, and opioids were the most commonly encountered agents.
Symptoms or clinical findings were documented in 71.1 % of patients. Of all
cases, 54.6 % required some form of medical treatment (antidotes, antivenom,
chelation, specific types of supportive care). This report serves as a
comprehensive survey of medical toxicology practice within participating
institutions. Prior trends continued to apply this year and indicate analgesic
(opioid and nonopioid), sedative-hypnotic/muscle relaxant agents, illicit drug
use, and ADRs continue to be major toxicological problems. Cases requiring
medical toxicology consultation in 2013 predominantly involved pharmaceuticals
and illicit drugs. Reasons for these drug exposures were diverse and included
intentional overdose, unintentional exposure, withdrawal syndromes, and ADRs.
Nonopioid analgesics, sedative-hypnotic agents, and opioids remained the most
frequently encountered agent classes. While over half of cases required some form
of medical treatment, fatalities were uncommon.
PMID- 25119254
TI - The three-dimensional shape analysis of the M1 segment of the middle cerebral
artery using MRA at 3T.
AB - INTRODUCTION: The M1 segment of the middle cerebral artery (MCA) is of great
importance to neurosurgery and interventional radiology. The purpose of this
study was to describe the M1 segment in three dimensions based on shape
projection using magnetic resonance angiography (MRA). METHODS: A three-view
method was established and used in the retrospective analysis of 717 M1 segments
derived from 3D-TOF MRA images. In this method, the M1 segment was first
projected on three orthogonal planes (axial, coronary, and sagittal plane); the
courses of the projected vessels were classified as line-shape, C-shape, or S
shape on each orthogonal plane; and then the actual parameters, including
internal diameter and so on, were measured on the projected images. The shape
classifications and the measured parameters were efficient methods of describing
the M1 segment. Twelve geometric models of the vessels were reconstructed and
were compared with those from an actual validation method. RESULTS: The 3D shape
of the M1 segment in the 3D orthogonal views was not uniform. Only 17.3 % M1
segments were straight, 43.5 % followed plane curves, and nearly 40 % were
tortuous in 3D space. The probability distributions of shape classifications
changed with age. The proportion of the tortuous vessels increased with age. We
also showed that the three-view method is effective with a volume relative error
of less than 13 %. CONCLUSION: The three-view method is convenient for describing
the 3D morphology, including the shape information, of the M1 segment. It is a
potential method for planning and predicting risk in
neurosurgery/neurointervention.
PMID- 25119253
TI - The effects of hemorrhagic parenchymal infarction on the establishment of sensori
motor structural and functional connectivity in early infancy.
AB - INTRODUCTION: The objective of the study was to characterize alterations of
structural and functional connectivity within the developing sensori-motor system
in infants with focal perinatal brain injury and at high risk of cerebral palsy.
METHODS: Functional magnetic resonance imaging (fMRI) and diffusion tensor
imaging (DTI) data were used to study the developing functional and structural
connectivity framework in six infants born prematurely at term equivalent age.
This was first characterised in three infants without focal pathology, which was
then compared to that derived from three infants with unilateral haemorrhagic
parenchymal infarction and a subsequent focal periventricular white matter lesion
who developed later haemiparesis. RESULTS: Functional responses to passive hand
movement were in the contralateral perirolandic cortex, regardless of focal
pathology. In infants with unilateral periventricular injury, afferent thalamo
cortical tracts appeared to have developed compensatory trajectories which
circumvented areas of damage. In contrast, efferent corticospinal tracts showed
marked asymmetry at term equivalent age following focal brain injury. Sensori
motor network analysis suggested that inter-hemispheric functional connectivity
is largely preserved despite pathology and that impairment may be associated with
adverse neurodevelopmental outcome. CONCLUSION: Following focal perinatal brain
injury, altered structural and functional connectivity is already present and can
be characterized with MRI at term equivalent age. The results of this small case
series suggest that these techniques may provide valuable new information about
prognosis and the pathophysiology underlying cerebral palsy.
PMID- 25119255
TI - Mechanical thrombectomy in patients with acute vertebrobasilar occlusion using
the Trevo device: a single-centre experience.
AB - INTRODUCTION: The purpose of this study is to investigate the efficacy and safety
of mechanical thrombectomy in patients with acute vertebrobasilar artery
occlusion (VBAO) using the Trevo StentrieverTM device. METHODS: Twenty patients
diagnosed with VBAO underwent digital subtraction angiography (DSA) with the
intention to perform mechanical thrombectomy with stent-retrievers between August
2011 and October 2013. Two patients were excluded because another device was
primarily used; in two other patients, thrombectomy was not possible. RESULTS:
Thrombectomy with the Trevo device was performed in 16 patients. The
StentrieverTM was used either as the sole device (56.3 %) or in conjunction with
up to four additional devices or techniques. Thirty-three clot retrieval
manoeuvres were performed (mean 2.1 +/- 1.3, range 1-5); the device could be
deployed and retrieved in all manoeuvres (100 %). No device-related complications
occurred. Mean duration of the endovascular intervention was 71.8 min (+/-39.9;
range 22-144). Complete or near complete recanalization (thrombolysis in cerebral
infarction (TICI) >=2b) was achieved in 13 patients (81.3 %). Eleven patients
(68.8 %) survived and seven patients (43.8 %) showed a good clinical outcome at
discharge, defined as modified Rankin Scale (mRS) 0-2 or National Institute of
Health Stroke Scale (NIHSS) improvement >=10 points. Including the two patients
in whom thrombectomy was not possible, successful recanalization, good clinical
outcome and survival were achieved in 72.2, 38.9 and 61.1 %, respectively.
CONCLUSIONS: Thrombectomy in patients with acute VBAO using the Trevo
StentrieverTM-either as the sole device or in conjunction with other devices-is
feasible and seems to be similarly effective and safe as in the anterior
circulation compared to reported data in the literature.
PMID- 25119257
TI - Transverse myelitis extended to disseminated encephalitis in systemic lupus
erythematosus: Histological evidence for vasculitis.
AB - A 42-year-old woman was admitted due to systemic lupus erythematosus complicated
with glomerulonephritis and pulmonary hypertension. During the treatment for
these complications, she presented motor paresis and sensory loss caused by
transverse myelitis. In spite of methyl prednisolone pulse therapy, she further
developed acute confusional state due to disseminated encephalitis and fell into
respiratory arrest. On laboratory examination, elevation of anti-NR2 antibodies
in serum as well as in cerebrospinal fluid was noted. Although she recovered from
the disseminated encephalitis after extensive treatment with high doses of
corticosteroid and intravenous cyclophosphamide, she suddenly died of pulmonary
hypertension. Autopsy findings confirmed the presence of liquefaction necrosis in
the entire circumference of the whole spinal cord along with intimal hyperplasia
and obliteration of the small arteries, accompanied by mononuclear cell
infiltration and disruption of internal elastic lamina. It is therefore most
likely that our patient developed longitudinal transverse myelitis through spinal
cord vasculitis, which extended to brainstem and brain parenchyma, leading to the
development of disseminated encephalitis.
PMID- 25119256
TI - Injury of the lower ascending reticular activating system in patients with
hypoxic-ischemic brain injury: diffusion tensor imaging study.
AB - INTRODUCTION: Many studies have reported on vulnerable areas and neural tracts of
the brain after hypoxic-ischemic brain injury (HI-BI). However, little is known
about injury of the ascending reticular activating system (ARAS). We attempted to
investigate on injury of the lower portion of the ARAS in patients with HI-BI
using diffusion tensor tractography (DTT). METHODS: Fourteen consecutive patients
with HI-BI and 10 control subjects were recruited for this study. We classified
the patients into two subgroups according to the preservation of arousal:
subgroup A (eight patients)-intact arousal and subgroup B (six patients)-impaired
arousal. The lower portion of the ARAS between the pontine reticular formation
and the thalamus was reconstructed using the probabilistic tractography method.
Fractional anisotropy (FA), mean diffusivity (MD), and tract volume (TV) were
measured. RESULTS: The FA value and TV were decreased in subgroup B compared with
those of the control group, although no difference was observed in the MD value
(p < 0.05). However, for all DTT parameters, no difference was observed between
subgroup A and the control group and between subgroup A and subgroup B (p >
0.05). CONCLUSION: Injury of the lower portion of the ARAS was found between the
pontine reticular formation and the thalamus in patients with impaired arousal
after HI-BI. We believe that analysis using DTT could be helpful in the
evaluation of patients with impaired arousal after HI-BI.
PMID- 25119258
TI - Are Sjogren's syndrome and IgG4-related disease able to coexist?
PMID- 25119259
TI - Ultrasonography and magnetic resonance imaging findings of rheumatoid arthritis
like arthritis in a patient with adult T-cell leukemia.
AB - A 43-year-old Japanese woman with adult T-cell leukemia (ATL) developed
rheumatoid arthritis-like polyarthritis with dermatitis and skin erosion. Her
rheumatoid factor and C-reactive protein results were positive. Musculoskeletal
ultrasonography showed intra-articular and peritendinous power Doppler signal
positive synovitis. Plain magnetic resonance imaging showed synovitis of the
above lesion and remarkable bone marrow edema/osteitis. She was diagnosed as
having ATL-associated arthritis based on the invasion of ATL cells by skin biopsy
at the arthritis lesion.
PMID- 25119260
TI - The roles of myeloid-derived suppressor cells in transplantation.
AB - CD11b(+)Gr1(+) myeloid-derived suppressor cells (MDSCs) are an important
regulatory innate cell population and have significant inhibitory effect on T
cell-mediated responses. In addition to their negative role in cancer
development, MDSCs also exert strong regulatory effects on transplantation and
autoimmunity. In many transplantation models, such as bone marrow transplant,
renal transplant, heart transplant and skin transplant settings, MDSCs accumulate
and have inhibitory effect on graft rejection. However, the inducing factors,
detailed phenotype and functional molecular mediators of MDSCs are significantly
different in various transplant models. With their strong suppressive activity,
MDSCs could become a potential clinical therapy during transplantation tolerance
induction and the combination of the MDSCs with other immunoregulatory cells or
immunosuppressive drugs is an intriguing protocol in the future. In this review,
we will summarize MDSC expansion, activation and induction in different
transplantation models and discuss the effects of immunoregulatory cells and
immunosuppressive drugs on MDSCs in transplant settings.
PMID- 25119261
TI - Facile and rapid synthesis of Pd nanodendrites for electrocatalysis and surface
enhanced Raman scattering applications.
AB - Numerous properties from metal nanostructures can be tuned by controlling both
their size and shape. In particular, the latter is extremely important because
the type of crystalline surface affects the surface electronic density. This
paper describes a simple approach to the synthesis of highly-structured,
anisotropic palladium nanostructured dendrites. They were obtained using an eco
friendly biomolecule 5-hydroxytryptophan, which acts as both a reducing and
stabilizing agent. The growth mechanism is proposed for the evolution of
dendrites morphology. It was found that the concentration of 5-hydroxytryptophan
played a vital role on the morphology of the nanostructured Pd dendrites. This
nanomaterial shows enhanced electrocatalytic performance towards the oxidation of
formic acid, and it exhibits surface-enhanced Raman scattering properties towards
the prostate specific antigen. These properties may be explored in fuel cells and
biosensors, respectively.
PMID- 25119262
TI - Spray pyrolysis of CZTS nanoplatelets.
AB - We demonstrate that copper-zinc-tin-sulphide nanoplatelets can be directly grown
onto a molybdenum-coated substrate using spray pyrolysis starting from a mixture
of metal thiocarbamates precursors. The structure and phase purity of the
nanoplatelets is discussed in detail.
PMID- 25119264
TI - Unusual assembly of lacunary heteropolymolybdates with cyanometalate fragment.
AB - Two new cyanide-bridged heteropolymolybdate complexes have been synthesized by a
facile self-assembly process in aqueous solution, which demonstrates a successful
tactic to incorporate the cyanometalate fragment into lacunary
heteropolymolybdate. Magnetic investigation showed that complex 2 exhibits slow
magnetic relaxation behavior.
PMID- 25119263
TI - Sex chromosomes and karyotype of the (nearly) mythical creature, the Gila
monster, Heloderma suspectum (Squamata: Helodermatidae).
AB - A wide variety of sex determination systems exist among squamate reptiles. They
can therefore serve as an important model for studies of evolutionary transitions
among particular sex determination systems. However, we still have only a limited
knowledge of sex determination in certain important lineages of squamates. In
this respect, one of the most understudied groups is the family Helodermatidae
(Anguimorpha) encompassing the only two venomous species of lizards which are
potentially lethal to human beings. We uncovered homomorphic ZZ/ZW sex
chromosomes in the Gila monster (Heloderma suspectum) with a highly
heterochromatic W chromosome. The sex chromosomes are morphologically similar to
the ZZ/ZW sex chromosomes of monitor lizards (Varanidae). If the sex chromosomes
of helodermatids and varanids are homologous, female heterogamety may be
ancestral for the whole Anguimorpha group. Moreover, we found that the karyotype
of the Gila monster consists of 2n = 36 chromosomes (14 larger metacentric
chromosomes and 22 acrocentric microchromosomes). 2n = 36 is the widely
distributed chromosomal number among squamates. In his pioneering works
representing the only previous cytogenetic examination of the family
Helodermatidae, Matthey reported the karyotype as 2n = 38 and suggested a
different chromosomal morphology for this species. We believe that this was
probably erroneously. We also discovered a strong accumulation of telomeric
sequences on several pairs of microchromosomes in the Gila monster, which is a
trait documented relatively rarely in vertebrates. These new data fill an
important gap in our understanding of the sex determination and karyotype
evolution of squamates.
PMID- 25119266
TI - Perspectives in pediatric pathology, chapter 1. Normal development of testicular
structures: from the bipotential gonad to the fetal testis.
PMID- 25119265
TI - Elucidating the role of DEPTOR in Alzheimer's disease.
AB - The mammalian or mechanistic target of rapamycin (mTOR) is a Ser/Thr protein
kinase that, in response to nutrient stimulation, regulates cellular growth,
proliferation, survival, protein synthesis and gene transcription. It has also
been implicated in Alzheimer's disease (AD) with neuronal cells and hippocampal
slices of AD transgenic mice experiencing dysregulated mTOR and synaptic
plasticity in response to treatment with the toxic amyloid beta (Abeta(1-42))
peptide, which has been implicated in AD. DEP domain-containing mTOR-interacting
protein (DEPTOR) is a protein which can bind to mTOR and cause its inhibition,
and functions as a regulatory protein of mTOR to control its activity. The
inhibition of mTOR has been shown to have a neuroprotective effect; in an animal
model, it was shown to protect against Abeta-induced neurotoxicity. In the
present study, to investigate to role of DEPTOR in a model of AD, we neuronally
differentiated the SH-SY5Y cell line and examined the effects of treatment with
an Abeta(42) peptide, thus mimicking plaque formation. This resulted in a
significant increase in mTOR and a significant decrease in DEPTOR expression
compared to the unstimulated controls. Moreover, to the best of our knowledge, we
demonstrate for the first time a reduction in the protein level of DEPTOR in the
precentral gyrus, postcentral gyrus and occipital lobe of a brain with AD
compared to a normal control, as well as a significant reduction in DEPTOR
expression in samples from late-onset AD (LOAD) compared to early-onset familial
AD (EOFAD). The reduction in DEPTOR expression in cases of AD compared to healthy
controls can lead to an augmentation of mTOR signalling, leading to Abeta
accumulation, which in turn leads to a further reduction in DEPTOR expression.
This results in the accumulation of amyloid plaque, shifting the balance from
neuroprotection to neurodegeneration.
PMID- 25119267
TI - Familiarity with interest breeds gossip: contributions of emotion, expectation,
and reputation.
AB - Although gossip serves several important social functions, it has relatively
infrequently been the topic of systematic investigation. In two experiments, we
advance a cognitive-informational approach to gossip. Specifically, we sought to
determine which informational components engender gossip. In Experiment 1,
participants read brief passages about other people and indicated their
likelihood to share this information. We manipulated target familiarity
(celebrity, non-celebrity) and story interest (interesting, boring). While
participants were more likely to gossip about celebrity than non-celebrity
targets and interesting than boring stories, they were even more likely to gossip
about celebrity targets embedded within interesting stories. In Experiment 2, we
additionally probed participants' reactions to the stories concerning emotion,
expectation, and reputation information conveyed. Analyses showed that while such
information partially mediated target familiarity and story interest effects,
only expectation and reputation accounted for the interactive pattern of gossip
behavior. Our findings provide novel insights into the essential components and
processing mechanisms of gossip.
PMID- 25119268
TI - Slow magnetic relaxation in a mononuclear eight-coordinate cobalt(II) complex.
AB - The quest for the single-molecular magnets (SMMs) based on mononuclear transition
metal complexes is focused on the low-coordinate species. No transition-metal
complex with a coordination number of eight has been shown to exhibit SMM
properties. Here the magnetic studies have been carried out for a mononuclear,
eight-coordinate cobalt(II)-12-crown-4 (12C4) complex [Co(II)(12C4)2](I3)2(12C4)
(1) with a large axial zero-field splitting. Magnetic measurements show field
induced, slow magnetic relaxation under an applied field of 500 Oe at low
temperature. The magnetic relaxation time tau was fitted by the Arrhenius model
to afford an energy barrier of Ueff = 17.0 cm(-1) and a preexponential factor of
tau0 = 1.5 * 10(-6) s. The work here presents the first example of the eight
coordinate, mononuclear, 3d metal complex exhibiting the slow magnetic
relaxation.
PMID- 25119272
TI - Vertebral artery dissection as cause of sulcal artery syndrome.
PMID- 25119269
TI - Development of a multi-species biotic ligand model predicting the toxicity of
trivalent chromium to barley root elongation in solution culture.
AB - Little knowledge is available about the influence of cation competition and metal
speciation on trivalent chromium (Cr(III)) toxicity. In the present study, the
effects of pH and selected cations on the toxicity of trivalent chromium
(Cr(III)) to barley (Hordeum vulgare) root elongation were investigated to
develop an appropriate biotic ligand model (BLM). Results showed that the
toxicity of Cr(III) decreased with increasing activity of Ca(2+) and Mg(2+) but
not with K(+) and Na(+). The effect of pH on Cr(III) toxicity to barley root
elongation could be explained by H(+) competition with Cr(3+) bound to a biotic
ligand (BL) as well as by the concomitant toxicity of CrOH(2+) in solution
culture. Stability constants were obtained for the binding of Cr(3+), CrOH(2+),
Ca(2+), Mg(2+) and H(+) with binding ligand: log KCrBL 7.34, log KCrOHBL 5.35,
log KCaBL 2.64, log KMgBL 2.98, and log KHBL 4.74. On the basis of those
estimated parameters, a BLM was successfully developed to predict Cr(III)
toxicity to barley root elongation as a function of solution characteristics.
PMID- 25119270
TI - Heterogeneous reactions of particulate matter-bound PAHs and NPAHs with NO3/N2O5,
OH radicals, and O3 under simulated long-range atmospheric transport conditions:
reactivity and mutagenicity.
AB - The heterogeneous reactions of ambient particulate matter (PM)-bound polycyclic
aromatic hydrocarbons (PAHs) and nitro-PAHs (NPAHs) with NO3/N2O5, OH radicals,
and O3 were studied in a laboratory photochemical chamber. Ambient PM2.5 and PM10
samples were collected from Beijing, China, and Riverside, California, and
exposed under simulated atmospheric long-range transport conditions for O3 and OH
and NO3 radicals. Changes in the masses of 23 PAHs and 20 NPAHs, as well as the
direct and indirect-acting mutagenicity of the PM (determined using the
Salmonella mutagenicity assay with TA98 strain), were measured prior to and after
exposure to NO3/N2O5, OH radicals, and O3. In general, O3 exposure resulted in
the highest relative degradation of PM-bound PAHs with more than four rings
(benzo[a]pyrene was degraded equally well by O3 and NO3/N2O5). However, NPAHs
were most effectively formed during the Beijing PM exposure to NO3/N2O5. In
ambient air, 2-nitrofluoranthene (2-NF) is formed from the gas-phase NO3 radical-
and OH radical-initiated reactions of fluoranthene, and 2-nitropyrene (2-NP) is
formed from the gas-phase OH radical-initiated reaction of pyrene. There was no
formation of 2-NF or 2-NP in any of the heterogeneous exposures, suggesting that
gas-phase formation of NPAHs did not play an important role during chamber
exposures. Exposure of Beijing PM to NO3/N2O5 resulted in an increase in direct
acting mutagenic activity which was associated with the formation of mutagenic
NPAHs. No NPAH formation was observed in any of the exposures of the Riverside
PM. This was likely due to the accumulation of atmospheric degradation products
from gas-phase reactions of volatile species onto the surface of PM collected in
Riverside prior to exposure in the chamber, thus decreasing the availability of
PAHs for reaction.
PMID- 25119273
TI - Acute orthostatic headache and diplopia due to a spinal subarachnoid haemorrhage.
PMID- 25119274
TI - Hemidystonia caused by frontal cortical infarction.
PMID- 25119275
TI - Mercury (Hg) in fish consumed by the local population of the Jaguaribe River
lower basin, Northeast Brazil.
AB - The knowledge of Hg concentrations in fish is of considerable interest since
these organisms are a major source of protein to coastal human populations and
fishing communities. The main source of human exposure to Hg contamination occurs
through the consumption of fish. In this paper, we compare Hg concentration in 13
fish species from Jaguaribe River lower basin and an adjacent coastal region in
the northeastern coast of Brazil. We sampled fish from three stretches of the
river: fluvial, estuarine, and marine regions. We tested the hypothesis that Hg
concentration in muscle tissue vary according to species, location, and trophic
level. Significant differences were observed among species and trophic level, but
these could not be observed among the regions studied. As expected, the highest
concentrations were observed in carnivorous fish (5.6-107.5; 26.9 +/- 18.8 ng g(
1)). Hg concentrations observed in this study are similar to those observed in
regions of low environmental contamination. We estimated Hg intake to vary
between 0.02 and 0.22 ng Hg kg body weight(-1) week(-1), for the average body
weight of 56.7 kg, which was considered as low exposure and therefore, a low risk
to consumers of fish from the regions studied.
PMID- 25119276
TI - Simultaneously degradation of 2,4-dichlorophenol and EDTA in aqueous solution by
the bimetallic Cu-Fe/O2 system.
AB - Oxidative degradation of aqueous organic contaminants 2,4-dichlorophenol (2,4
DCP) using ethylenediaminetetraacetic acid (EDTA)-enhanced bimetallic Cu-Fe
system in the presence of dissolved oxygen was investigated. The proposed process
was applied for the pH range of 3~7 with the degradation efficiency of 2,4-DCP
and EDTA varying within 10 %, and achieved at 100 % degradation of 40 mg L(-1)
2,4-DCP in 1 h, at the initial pH of 3, 25 g L(-1) of bimetallic Fe-Cu powder
(WCu/WFe = 0.01289) and initial EDTA of 0.57 mM. However, the removal efficiency
of 2,4-DCP in control tests were 7.52 % (Cu-Fe/O2 system) and 84.32 % (EDTA
enhanced Fe/O2 process), respectively, after 3 h, reaction. The proposed main
mechanism, involves the in situ generation of H2O2 by the electron transfer from
Fe(0) to O2 which was enhanced by ethylenediaminetetraacetic acid (EDTA), and the
in situ generation of .OH via advanced oxidation reaction. Accordingly, 2,4-DCP
was attacked by .OH to achieve complete dechlorination and low molecular weight
organic acids, even mineralized. Systematic studies on the effects of initial
EDTA and 2,4-DCP concentration, Cu-Fe dosing, Cu content, and pH revealed that
these effects need to be optimized to avoid the excessive consumption of .OH and
new EDTA and heavy metal Cu pollution.
PMID- 25119277
TI - Insights into community-based discrimination of water quality status using an
annual pool of phytoplankton in mid-subtropical canal systems.
AB - With rapid response to environmental changes, phytoplankton communities have been
used as a favorable bioindicator to evaluate environmental stress and
anthropogenic impacts in aquatic ecosystems. The feasibility for their community
based bioassessment was studied in a mid-subtropical canal (Tiesha River),
southern China, during a 1-year cycle (November 2009-December 2010). Samples were
monthly collected at four sampling stations within a contamination gradient.
Environmental variables, such as water temperature, dissolved oxygen (DO),
chemical oxygen demand (COD), biological oxygen demand (BOD5), total phosphorus
(TP), and total nitrogen (TN), were measured synchronously for comparison with
biotic parameters. The phytoplankton community structures showed a significant
difference among four stations. The spatial variation in abundance was
significantly correlated with the changes in environmental variables, especially
TN, TP, and COD. Four dominant species (Aulacoseira granulata, Leptocylindrus
danicus, Oscillatoria tenuis, and Radiococcus nimbatus) were significantly
correlated with nutrients, while the species richness index represented a
significant correlation with BOD5. The phytoplankton-based Saprobien indices
could not reveal the spatial variation in water quality status although may
reflect water pollution levels (from beta- to alpha-mesosaprobic zone) in the
canal system. It is suggested that phytoplankton communities might be used as a
potentially robust bioindicator for discriminating environmental quality status
in mid-tropical canal systems.
PMID- 25119278
TI - The minimum detectable difference (MDD) and the interpretation of treatment
related effects of pesticides in experimental ecosystems.
AB - In the European registration procedure for pesticides, microcosm and mesocosm
studies are the highest aquatic experimental tier to assess their environmental
effects. Evaluations of microcosm/mesocosm studies rely heavily on no observed
effect concentrations (NOECs) calculated for different population-level
endpoints. Ideally, a power analysis should be reported for the concentration
response relationships underlying these NOECs, as well as for measurement
endpoints for which significant effects cannot be demonstrated. An indication of
this statistical power can be provided a posteriori by calculated minimum
detectable differences (MDDs). The MDD defines the difference between the means
of a treatment and the control that must exist to detect a statistically
significant effect. The aim of this paper is to expand on the Aquatic Guidance
Document recently published by the European Food Safety Authority (EFSA) and to
propose a procedure to report and evaluate NOECs and related MDDs in a harmonised
way. In addition, decision schemes are provided on how MDDs can be used to assess
the reliability of microcosm/mesocosm studies and for the derivation of effect
classes used to derive regulatory acceptable concentrations. Furthermore,
examples are presented to show how MDDs can be reduced by optimising experimental
design and sampling techniques.
PMID- 25119279
TI - Root morphological responses of three hot pepper cultivars to Cd exposure and
their correlations with Cd accumulation.
AB - Cultivars of hot pepper (Capsicum annuum L.) differ widely in their fruit cadmium
(Cd) concentrations. Previously, we suggested that low-Cd cultivars are better
able to prevent the translocation of Cd from roots to aboveground parts, but the
corresponding mechanisms are still unknown. In this study, we aimed to improve
understanding of the root morphological characteristics of the mechanisms
involved in two low-Cd and a high-Cd cultivar. Seedlings were grown in nutrient
solutions containing 0 (control), 2, and 10 MUM Cd for 20 days, and Cd contents
for the three cultivars were compared with changes in root morphology. The total
root length (RL), root surface area (SA), number of root tips (RT), and specific
root length (SRL) of all cultivars were decreased significantly by the 10 MUM Cd
treatment with the exception of the SA in JFZ, which showed no obvious change.
For each cultivar, the 10 MUM Cd treatment decreased significantly RL and SA
specifically in roots with diameters (RD) of RD <= 0.2 mm or 0.2 mm < RD <= 0.4
mm, and increased significantly RL and SA specifically in roots with diameters of
0.6 mm < RD <= 0.8 mm. Hot pepper cultivars differ greatly in Cd accumulation and
root morphology. In the 10 MUM Cd treatment, root volume (RV), SA, and RT of all
cultivars were negatively correlated with Cd concentration and amount in roots.
However, RL, SA, RV, and RT of all cultivars were positively correlated with Cd
concentration and amount in shoots, and translocation rate of Cd. The two low-Cd
cultivars of hot pepper had less root tips, shorter root length, and smaller root
surface area than the high-Cd cultivar in 10 MUM Cd treatment, which may play a
vital role in reducing root-to-shoot Cd translocation.
PMID- 25119280
TI - How do two giant panda populations adapt to their habitats in the Qinling and
Qionglai Mountains, China.
AB - The spatial separation of the Qinling Mountains from the western mountains has
caused morphological and genetic distinctions of giant pandas. Could this
separation also cause the pandas' behavior change? In this research, we focused
on the pandas' movement pattern and selected two wild panda groups in Foping and
Wolong Nature Reserves (NR) to represent the populations in the Qinling and
Qionglai Mountains, respectively. We hypothesized that the Qinling pandas have
developed a different seasonal movement pattern compared with the pandas in the
western mountains. We analyzed the radio tracking data from two NRs by using GIS.
Our results showed the following significant differences: (1) The Foping pandas
live most of the year in the low elevation areas and move higher during June and
remain through August while the Wolong pandas live most of the year in the high
elevation areas and move lower in April and stay through June; (2) Comparing
their low and high elevational areas shows the distinct spatial patterns between
reserves, forming two obviously separated clusters in Foping but a single-compact
cluster in Wolong; (3) Foping pandas move an average of 425 m +/- 147 s.d. daily,
while Wolong pandas move an average of 550 m +/- 343 s.d. daily; and (4) Three
habitat factors (i.e., terrain, temperature, and bamboo nutrient) were taken as
the driving forces and analyzed, and they showed a strong support explanation to
these different movement behaviors of pandas in two NRs. Our findings have
important implications for management, for instance, it needs to be careful
considering the behavior difference of the pandas when reintroducing them to the
wild.
PMID- 24839579
TI - Greetings from the editor-in-chief.
PMID- 24839580
TI - The Korea National Health and Nutrition Examination Survey (KNHANES): current
status and challenges.
PMID- 25055010
TI - WHO Western Pacific regional action plan for the prevention and control of NCDs
(2014-2020).
PMID- 24904754
TI - T cell immunosenescence, hypertension, and arterial stiffness.
PMID- 25119285
TI - NHC-AuCl/selectfluor: a highly efficient catalytic system for carbene-transfer
reactions.
AB - The combination of NHC-gold complex and Selectfluor has been found to be a highly
efficient catalyst system for carbene-transfer reactions, with a turnover number
(TON) up to 990000 and a turnover frequency (TOF) up to 82500 h(-1).
PMID- 25119286
TI - Optical modulation of waveguiding in spiropyran-functionalized polydiacetylene
microtube.
AB - Optical modulation of waveguiding and logic operations play significant roles in
highly integrated optical communication components, optical computing, and
photonic circuits. Herein, we designed and synthesized spiropyran-functionalized
polydiacetylene (SFPDA) microtubes, and realized reversible optical modulation of
waveguiding in SFPDA microtubes through fluorescence resonance energy transfer
(FRET) between the PDA matrix and spiropyran in open merocyanine (MC) form within
the surface of the microtubes. Because of the reversible isomerization
characteristics of spiropyran units, we have realized resettable, multireadout
logic system that includes OR and INHIBIT logic operations in SFPDA microtube.
PMID- 25119287
TI - Novel one-, two-, and three-dimensional selenidostannates templated by iron(II)
complex cation.
AB - The novel iron selenidostannates [Fe(bipy)3]Sn4Se9.2H2O (1) and
[Fe(bipy)3]2[Sn3Se7]2.bipy.2H2O (2) (bipy = bipyridine) were prepared by the
reactions of Sn, Se, FeCl2.4H2O, bipy, and dien with/without KSCN under
hydrothermal conditions (dien = diethylenetriamine). In 1, four SnSe5 units
condense via edge sharing to form the novel 3-D framework selenidostannate
(infinity)3[Sn4Se92-] containing an interpenetrating channel system. The
[Fe(bipy)3]2+ cations are accommodated in the different channels according to the
conformation of the [Fe(bipy)3]2+ cation. In 2, three SnSe5 units share edges to
form a 2-D (infinity)2[Sn3Se72-] layered anion, while two SnSe5 units and one
SnSe4 unit are connected via edge sharing, forming a 1-D (infinity)1[Sn3Se72-]
chainlike anion. The (infinity)1[Sn3Se72-], [Fe(bipy)3]2+, bipy, and H2O species
are embedded between the (infinity)2[Sn3Se72-] layers. 2 is the first example of
a selenidostannate constructed by both (infinity)2[Sn3Se72-]and
(infinity)1[Sn3Se72-] anions. The coexistence of 1-D (infinity)1[Sn3Se72-] and 2
D (infinity)2[Sn3Se72-] anions in 2 might support the possible reaction mechanism
that the (infinity)2[Sn3Se72-] anions are formed by condensation of the
(infinity)1[Sn3Se72-] chains. 1 and 2 exhibit band gaps at 1.43 and 2.01 eV,
respectively.
PMID- 25119288
TI - Viscous friction between crystalline and amorphous phase of dragline silk.
AB - The hierarchical structure of spider dragline silk is composed of two major
constituents, the amorphous phase and crystalline units, and its mechanical
response has been attributed to these prime constituents. Silk mechanics,
however, might also be influenced by the resistance against sliding of these two
phases relative to each other under load. We here used atomistic molecular
dynamics (MD) simulations to obtain friction forces for the relative sliding of
the amorphous phase and crystalline units of Araneus diadematus spider silk. We
computed the coefficient of viscosity of this interface to be in the order of
10(2) Ns/m(2) by extrapolating our simulation data to the viscous limit.
Interestingly, this value is two orders of magnitude smaller than the coefficient
of viscosity within the amorphous phase. This suggests that sliding along a
planar and homogeneous surface of straight polyalanine chains is much less
hindered than within entangled disordered chains. Finally, in a simple finite
element model, which is based on parameters determined from MD simulations
including the newly deduced coefficient of viscosity, we assessed the frictional
behavior between these two components for the experimental range of relative
pulling velocities. We found that a perfectly relative horizontal motion has no
significant resistance against sliding, however, slightly inclined loading causes
measurable resistance. Our analysis paves the way towards a finite element model
of silk fibers in which crystalline units can slide, move and rearrange
themselves in the fiber during loading.
PMID- 25119289
TI - Longitudinal hemodynamic measurements in swine heart failure using a fully
implantable telemetry system.
AB - Chronic monitoring of heart rate, blood pressure, and flow in conscious free
roaming large animals can offer considerable opportunity to understand the
progression of cardiovascular diseases and can test new diagnostics and
therapeutics. The objective of this study was to demonstrate the feasibility of
chronic, simultaneous measurement of several hemodynamic parameters (left
ventricular pressure, systemic pressure, blood flow velocity, and heart rate)
using a totally implantable multichannel telemetry system in swine heart failure
models. Two solid-state blood pressure sensors were inserted in the left
ventricle and the descending aorta for pressure measurements. Two Doppler probes
were placed around the left anterior descending (LAD) and the brachiocephalic
arteries for blood flow velocity measurements. Electrocardiographic (ECG)
electrodes were attached to the surface of the left ventricle to monitor heart
rate. The telemeter body was implanted in the right side of the abdomen under the
skin for approximately 4 to 6 weeks. The animals were subjected to various heart
failure models, including volume overload (A-V fistula, n = 3), pressure overload
(aortic banding, n = 2) and dilated cardiomyopathy (pacing-induced tachycardia, n
= 3). Longitudinal changes in hemodynamics were monitored during the progression
of the disease. In the pacing-induced tachycardia animals, the systemic blood
pressure progressively decreased within the first 2 weeks and returned to
baseline levels thereafter. In the aortic banding animals, the pressure
progressively increased during the development of the disease. The pressure in
the A-V fistula animals only showed a small increase during the first week and
remained stable thereafter. The results demonstrated the ability of this
telemetry system of long-term, simultaneous monitoring of blood flow, pressure
and heart rate in heart failure models, which may offer significant utility for
understanding cardiovascular disease progression and treatment.
PMID- 25119290
TI - ATF3 and extracellular matrix-related genes associated with the process of
chronic obstructive pulmonary.
AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a major public
health problem worldwide and is proved to be the number three cause of death in
globally. The objective of this study was to explore the molecular mechanism of
the progression of COPD. METHODS: Using the GSE1650 affymetrix microarray data
accessible from Gene Expression Omnibus database, we first identified the
differentially expressed genes (DEGs) between 18 COPD samples and 12 normal
samples, followed by the GO / KEGG pathway analysis and gene interaction networks
analysis of the DEGs. Our study identified 134 DEGs which involved in regulation
of immune response, vesicle transport system, growth regulator and extracellular
matrix (ECM)-related pathways. RESULTS: Gene interaction networks analysis showed
that the sub-network involved by activating transcription factor-3 (ATF3) was the
most significant sub-network in gene interaction networks. Furthermore, the
investigation of extracellular matrix-related genes showed that genes like
collagen and insulin-like growth factor binding protein could clearly distinguish
the COPD and normal control. CONCLUSIONS: The genes regulated by ATF3
transcriptional activator as well as ECM-related genes may play an important role
in the process of COPD. Our study provides a comprehensive bioinformatics
analysis of genes and pathways which may be involved in the progression of COPD.
PMID- 25119291
TI - Feasibility of using the nasal route for linear endobronchial ultrasound.
AB - PURPOSE: Linear endobronchial ultrasound (EBUS) is a safe and accurate diagnostic
test for mediastinal adenopathy. Its feasibility through the nasal route has not
been reported. The objective of this study was to document the feasibility of
linear EBUS using the nasal route and compare its accuracy and safety with the
oral route. METHODS: A retrospective analysis of consecutive subjects who
underwent an EBUS procedure under conscious sedation at our center was conducted.
Nasal insertion of the bronchoscope was attempted in all subjects; the oral route
was used in case of failed nasal insertion. Characteristics of the procedure and
the diagnostic accuracy of EBUS were compared between the two insertion routes.
RESULTS: From May to October 2012, 209 subjects underwent an EBUS. Complete data
were available for 196 subjects. Nasal insertion of the EBUS bronchoscope was
possible in 73.5 %. There was no difference between the two insertion routes in
the location and number of stations sampled per subject. Procedure duration and
complications (epistaxis, bronchial bleeding, desaturation, and pneumothorax)
were similar between the two groups (2.1 % for nasal group vs 1.9 % for oral
group). Minor epistaxis occurred in one subject in the nasal group. Comparing the
nasal and oral groups, rates of adequate specimens were similar (90.5 vs 88.9 %,
respectively; p = 0.68), and proportions of diagnostic specimens were not
statistically different (51.4 vs 42.3 %, respectively; p = 0.26). CONCLUSION:
Linear EBUS can be performed safely and with high accuracy via the nasal route.
Controlled studies are required to determine which insertion route provides best
patient comfort.
PMID- 25119292
TI - Service, training and outreach--the EARS Inc. Model for a self sustainable
hearing program in action.
AB - PURPOSE: EARS Inc. is a faith based not-for-profit organization established in
1998. As an organization, it has consistently maintained a goal to provide both
short-term and long-term projects in low and middle income countries. One
specific project undertaken by EARS Inc involved developing a hearing health
program in the Dominican Republic. METHODS: This article is a review of the
challenges and successes encountered on the road to establishing improved access
and affordability of hearing aid technology for the hearing impaired in Domincan
Republic. RESULTS: Despite the challenges, after 12 years of local programming,
the hearing health services in the Dominican Republic were successfully
implemented. The development of these services included the simultaneous
development of a training program, earmould laboratory, hearing aid repair
services as well as calibration services and sales of batteries and accessories.
CONCLUSIONS: As demonstrated in this review, it is possible to develop
sustainable and comprehensive diagnostic and rehabilitation hearing services in a
developing country. It is clear that training, equipping and empowering local
staffs are instrumental to the success of the program. IMPLICATIONS FOR
REHABILITATION: A good hearing aid fitting is more than supplying technology.
Patient education and the clinician fitting the hearing aid are important. Access
to follow-up services including battery supplies, hearing aid adjustments and
hearing aid repairs is essential for a hearing aid fitting program in low and
middle income countries to be sustainable. Check the WHO guidelines for hearing
aid provision in developing countries when planning a program. When working in a
country, co-ordinate with local professionals involved in hearing health where
available.
PMID- 25119293
TI - Developing self-sustainable hearing centers in the developing world--case study
of EARs Inc project in Dominican Republic.
AB - PURPOSE: This paper presents the case study of the project EARS Ind developed in
the Dominican Republic (DR) with the purpose of increasing access and
affordability of hearing aid technology for the hearing impaired. This case study
demonstrates how a program can fit hearing aids to patients with hearing
impairments can be developed in low and middle income countries. METHODS: The
project planning documents and project statistics and reports were reviewed. A
questionnaire and follow-up interviews were used to gain a clear understanding of
the situation in the EARS Inc. DR hearing aid project. RESULTS: The case study is
presented of the development and services in the DR with a particular focus on
the choices made in regard to hearing aid services including manufacturer
choices, procurement, distribution, pricing and service delivery. The development
of these services included the simultaneous development of a training program,
ear mould laboratory, hearing aid repair services, also sales of batteries and
accessories as well as the development of calibration services. CONCLUSIONS: The
development of comprehensive diagnostic and rehabilitation services requires
equipping and training local staff. IMPLICATIONS FOR REHABILITATION: A good
hearing aid fitting is more than technology--patient education and the clinician
fitting the hearing aid are important. Access to follow-up services including
battery supplies, hearing aid adjustments and hearing aid repairs is essential to
any hearing aid fitting program in low and middle income countries. Check the WHO
guidelines for hearing aid provision in developing countries when planning a
program. When working in a country co-ordinate with local professional involved
in hearing health where available.
PMID- 25119294
TI - Cell oxidation-reduction imbalance after modulated radiofrequency radiation.
AB - Aim of this study was to evaluate an influence of modulated radiofrequency field
(RF) of 1800 MHz, strength of 30 V/m on oxidation-reduction processes within the
cell. The assigned RF field was generated within Gigahertz Transversal
Electromagnetic Mode cell equipped by signal generator, modulator, and amplifier.
Cell line V79, was irradiated for 10, 30, and 60 min, specific absorption rate
was calculated to be 1.6 W/kg. Cell metabolic activity and viability was
determined by MTT assay. In order to define total protein content, colorimetric
method was used. Concentration of oxidised proteins was evaluated by enzyme
linked immunosorbent assay. Reactive oxygen species (ROS) marked with fluorescent
probe 2',7'-dichlorofluorescin diacetate were measured by means of plate reader
device. In comparison with control cell samples, metabolic activity and total
protein content in exposed cells did not differ significantly. Concentrations of
carbonyl derivates, a product of protein oxidation, insignificantly but
continuously increase with duration of exposure. In exposed samples, ROS level
significantly (p < 0.05) increased after 10 min of exposure. Decrease in ROS
level was observed after 30-min treatment indicating antioxidant defence
mechanism activation. In conclusion, under the given laboratory conditions,
modulated RF radiation might cause impairment in cell oxidation-reduction
equilibrium within the growing cells.
PMID- 25119296
TI - Regioselective synthesis of enones via a titanium-promoted coupling of
unsymmetrical alkynes with weinreb amides.
AB - A modular titanium-promoted coupling of unsymmetrical internal alkynes with
Weinreb amides is described. The coupling reaction takes place at room
temperature and affords E-trisubstituted enones in moderate to good yields with
high levels of regioselectivity. The system shows moderate chemoselectivity.
PMID- 25119295
TI - A small molecule restores function to TRPML1 mutant isoforms responsible for
mucolipidosis type IV.
AB - Mucolipidosis type IV (MLIV) is an autosomal recessive lysosomal storage disorder
often characterized by severe neurodevelopmental abnormalities and neuro-retinal
degeneration. Mutations in the TRPML1 gene are causative for MLIV. We used lead
optimization strategies to identify--and MLIV patient fibroblasts to test--small
molecule activators for their potential to restore TRPML1 mutant channel
function. Using the whole-lysosome planar patch-clamp technique, we found that
activation of MLIV mutant isoforms by the endogenous ligand PI(3,5)P2 is strongly
reduced, while activity can be increased using synthetic ligands. We also found
that the F465L mutation renders TRPML1 pH insensitive, while F408Delta impacts
synthetic ligand binding. Trafficking defects and accumulation of zinc in
lysosomes of MLIV mutant fibroblasts can be rescued by the small molecule
treatment. Collectively, our data demonstrate that small molecules can be used to
restore channel function and rescue disease associated abnormalities in patient
cells expressing specific MLIV point mutations.
PMID- 25119297
TI - Pneumocystis jirovecii pneumonia under everolimus in two patients with metastatic
pancreatic neuroendocrine tumors.
AB - BACKGROUND: Everolimus, an mTOR inhibitor with immunosuppressive properties, is
used in several types of advanced tumors. Materials and METHODS: We describe the
first two cases of Pneumocystis jirovecii pneumonia in patients given everolimus
for metastatic pancreatic neuroendocrine tumors. RESULTS: The first patient
presented with respiratory symptoms in the context of grade 4 lymphopenia 2 weeks
after starting everolimus; the diagnosis of Pneumocystis jirovecii pneumonia was
made post-mortem. After suspecting everolimus-related interstitial pneumonitis in
the second patient, Pneumocystis jirovecii was detected, and cotrimoxazole
therapy led to a favorable outcome. CONCLUSION: Everolimus may induce
pneumonitis, lymphopenia and opportunistic infections. The time from treatment
initiation to opportunistic infection may be short. Risk factors in oncology
deserve further identification in order to start prophylaxis without delay.
PMID- 25119299
TI - Fundamental study of a real-time occupational dosimetry system for interventional
radiology staff.
AB - Real-time monitoring of the radiation doses received by interventional radiology
(IR) staff has become highly desirable. However, occupational doses are rarely
measured in real time, due to the lack of a feasible method for use in IR.
Recently, the i2 system by RaySafeTM has been introduced to measure occupational
exposure in IR in real time. The i2 system consists of several personal
dosimeters (PDs) and a base station with a display and computer interfacing. We
evaluated the fundamental performance (dose linearity, dose-rate dependence,
angular dependence, batch uniformity and reproducibility) of the i2 system. The
dose linearity of the i2 was excellent (R(2) = 1.00) The i2 exhibited slight dose
rate dependence (~20%) at very high dose rates (250 mGy h(-1)). Little angular
dependence (within 20%) was observed between 0 degrees and +/-45 degrees , in
either the vertical or horizontal direction. We also found that the PD was highly
sensitive (about 200%) at angles behind it, e.g. 180 degrees . However, this
backscattered radiation is not a problem, in general, due to the placement of the
i2 sensor (PD) on the lead apron. We conclude that the i2 system facilitates
accurate real-time monitoring and management of occupational doses during IR.
PMID- 25119298
TI - A proteinaceous fraction of wheat bran may interfere in the attachment of
enterotoxigenic E. coli K88 (F4+) to porcine epithelial cells.
AB - Wheat bran (WB) from Triticum aestivum has many beneficial effects on human
health. To the best of our knowledge, very little has been published about its
ability to prevent pathogenic bacterial adhesion in the intestine. Here, a WB
extract was fractionated using different strategies, and the obtained fractions
were tested in different in vitro methodologies to evaluate their interference in
the attachment of enterotoxigenic Escherichia coli (ETEC) K88 to intestinal
porcine epithelial cells (IPEC-J2) with the aim of identifying the putative anti
adhesive molecules. It was found that a proteinaceous compound in the >300-kDa
fraction mediates the recognition of ETEC K88 to IPEC-J2. Further fractionation
of the >300-kDa sample by size-exclusion chromatography showed several proteins
below 90 kDa, suggesting that the target protein belongs to a high-molecular
weight (MW) multi-component protein complex. The identification of some relevant
excised bands was performed by mass spectrometry (MS) and mostly revealed the
presence of various protease inhibitors (PIs) of low MW: Serpin-Z2B, Class II
chitinase, endogenous alpha-amylase/subtilisin inhibitor and alpha
amylase/trypsin inhibitor CM3. Furthermore, an incubation of the WB extract with
ETEC K88 allowed for the identification of a 7S storage protein globulin of
wheat, Globulin 3 of 66 kDa, which may be one of the most firmly attached WB
proteins to ETEC K88 cells. Further studies should be performed to gain an
understanding of the molecular recognition of the blocking process that takes
place. All gathered information can eventually pave the way for the development
of novel anti-adhesion therapeutic agents to prevent bacterial pathogenesis.
PMID- 25119301
TI - An electrochemical immunosensor based on interdigitated array microelectrode for
the detection of chlorpyrifos.
AB - An electrochemical immunosensor based on interdigitated array microelectrodes
(IDAMs) was developed for sensitive, specific and rapid detection of
chlorpyrifos. Anti-chlorpyrifos monoclonal antibodies were orientedly immobilized
onto the gold microelectrode surface through protein A. Chlorpyrifos were then
captured by the immobilized antibody, resulting in an impedance change in the
IDAMs surface. Electrochemical impedance spectroscopy was used in conjunction
with the fabricated sensor to detect chlorpyrifos. Under optimum conditions, the
impedance value change of chlorpyrifos was proportional to its concentrations in
the range of 10(0)-10(5) ng/mL. The detection limit was found to be 0.014 ng/mL
for chlorpyrifos. The proposed chlorpyrifos immunosensor could be used as a
screening method in pesticide determination for the analysis of environmental,
agricultural and pharmaceutical samples due to its rapidity, sensitivity and low
cost.
PMID- 25119302
TI - Epimorphin expression in a rat model of pulmonary hypoplasia associated with
congenital diaphragmatic hernia.
AB - PURPOSE: The pathogenesis of pulmonary hypoplasia associated with congenital
diaphragmatic hernia (CDH) remains unclear. Interactions between the epithelium
and surrounding mesenchyme play an important role in normal lung morphogenesis.
Epimorphin, a stromal protein, plays a role in epithelial morphogenesis and lung
branching, both of which are involved in pulmonary hypoplasia. In this study, we
aimed to examine the relationship between epimorphin and pulmonary hypoplasia
associated with CDH in an animal model. METHODS: Time-pregnant rats were exposed
to nitrofen or vehicle on gestational day 9 (D9). Fetuses were harvested on D16
and D20, and were divided into control, hypoplastic lungs with CDH (CDH+), and
hypoplastic lungs without CDH (CDH-). Both lungs of each fetus were removed and
subjected to morphometric and molecular biologic analyses. Lung-to-body weight
ratios were calculated. Pulmonary RNA was extracted, and relative mRNA level of
epimorphin was determined by quantitative real-time PCR (qRT-PCR). Protein
expression of epimorphin was investigated by Western blotting. RESULTS: In groups
D16 and D20, lung-to-body weight ratios in subgroups CDH+ were significantly
lower than those of controls and CDH-. The relative mRNA expression levels of
epimorphin were significantly increased in both lungs in subgroup CDH+ compared
with controls and CDH- on D16. Pulmonary epimorphin gene expression levels were
significantly decreased in CDH+ group on D20 compared to controls. Western
blotting confirmed the qRT-PCR results showing decreased pulmonary epimorphin
protein expression in CDH+ hypoplastic lungs compared to controls on D20.
CONCLUSION: Our study shows that there is an association between the epimorphin
expression and pulmonary hypoplasia associated with CDH. Although the cause
effect relationship is far from being established, epimorphin-related mechanisms
have a more critical role in early (D16) developmental stage.
PMID- 25119303
TI - "Spiral intestinal lenghtening and tailoring (SILT)" for a child with severely
short bowel.
AB - We report a child with post-surgical short bowel state who underwent bowel
expansion followed by spiral intestinal lengthening and tailoring (SILT) at 10
months of age. Growth at 1-year follow-up is along the 15-25th centile on 82 %
oral calories as normal diet and 18 % as parenteral nutrition, and he is passing
2-3 semisolid motions daily. SILT is a versatile technique for reconstructing
dilated bowel towards improved propulsion and absorption, and has a role in the
management of the short bowel state.
PMID- 25119305
TI - Georg Buchner, Sigmund Freud and the "Schadelnerven" (cranial nerves) - research
on the brain and soul in the 19th century.
AB - BACKGROUND: One of the authors' encounter with one of Sigmund Freud's original
works about the anatomy of the human brain stem and his interest in the
scientist, anatomist, philosopher, writer and revolutionary Georg Buchner led to
re-examination and review of the original writings of two major 19th century
protagonists of brain anatomy research. The aim of the authors is to highlight
the achievements of both Freud and Buchner in the field of comparative brain
morphology. METHODS: The medical and philosophical publications of Georg Buchner
were reviewed with reference to the historical-critical edition of his complete
works and writings (the so-called Marburg edition). Evaluation of the
neuroanatomical achievements of Sigmund Freud was based on a summary of his
publications and also partially on his autobiographical writings. RESULTS: After
careful review of their publications both Freud and Buchner should be
acknowledged as brain scientists focusing particularly on comparative morphology.
Both chose fish as the subject of their macroscopic (Buchner) and microscopic
(Freud) neuroanatomical studies, and both cut across their own language and
cultural space by continuing their work in France. In interpreting their findings
both were influenced by their respective contemporary methodological schools of
thought. Buchner became a soul scientist/psychologist by turning to the writing
of literary texts, heralding the end of his idealistic and metaphysical
interpretation of life. Likewise, Freud increasingly devoted himself to the
destiny of man and his "conditio humana," eventually turning away from anatomical
brain research. CONCLUSION: Review of the biographies and medical-scientific, as
well as philosophical publications, of Georg Buchner and Sigmund Freud reveal
striking parallels between the two researchers in addition to common insights
that have generally been ignored or only marginally addressed in the past. Both
should be appreciated and remembered as forerunners of today's neuroscientific
community.
PMID- 25119306
TI - [Rare cause of an abdominal emergency--case 6/2014].
AB - HISTORY AND ADMISSION FINDINGS: We report on a 58-year-old male patient with
abdominal and right-sided flank pain, who presented with the picture of an acute
abdominal emergency. INVESTIGATIONS: Laboratory tests revealed evidence of an
inflammation and a hematuria. In the Doppler duplex ultrasound and computed
tomography, chronic idiopathic periaortitis was diagnosed. The inflammatory
fibrosing disease resulted in urine retention and rupture of the fornix of the
right kidney. DIAGNOSIS, TREATMENT AND COURSE: After surgical implementation of
an ureteral stent and initiation of immunosuppressive therapy, it came to an
improvement of the symptoms. CONCLUSIONS: In the differential diagnosis of an
acute abdominal emergency, diseases of the aorta should be taken into account.
Especially in male patients with anatomical complications it is important to
exclude an inflammatory-fibrosing disease.
PMID- 25119307
TI - Identification of a novel HOG1 homologue from an industrial glycerol producer
Candida glycerinogenes.
AB - Candida glycerinogenes, a glycerol production industrial strain with hyperosmo
adaptation can grow well in 15 % (w/v) NaCl or 55 % (w/v) glucose. To understand
the osmo-adaptation mechanism in C. glycerinogenes, the mitogen-activated protein
kinase HOG1 gene (CgHOG1), which plays an essential role in the yeast
hyperosmotic response, was isolated by degenerate PCR and SEFA-Formed Adaptor
PCR. The CgHOG1 gene was then transformed in Saccharomyces cerevisiae hog1Delta
null mutant, which restored the recombination S. cerevisiae to the wild-type
phenotype with osmo-adaptation. To further clarify the function of CgHOG1, the
phosphorylation of CgHOG1 and transcription of the glycerol-3-phosphate
dehydrogenase gene (GPD1) of the CgHOG1-harbouring S. cerevisiae mutant was
detected, and found to be similar to that of wild-type S. cerevisiae. In
addition, the recombination S. cerevisiae with CgHOG1 gene significantly
accumulated intracellular glycerol when stressed with NaCl.
PMID- 25119308
TI - Acid resistance contributes to the high-pressure carbon dioxide resistance of
Escherichia coli K-12.
AB - Effect of deletion of acid resistant genes of E. coli on the high-pressure carbon
dioxide (HPC) resistance was investigated. Genes coding amino acid
decarboxylases, such as lysine, arginine, and glutamate decarboxylase, were found
to contribute to HPC resistance. Protonophore-treated cells showed
hypersensitivity to HPC, confirming that HPC induced cytoplasm acidification and
exerted severe damage on cells by intrusion of gaseous carbon dioxide into
cytoplasm.
PMID- 25119304
TI - The effects of healthy aging, amnestic mild cognitive impairment, and Alzheimer's
disease on recollection and familiarity: a meta-analytic review.
AB - It is well established that healthy aging, amnestic Mild Cognitive Impairment
(aMCI), and Alzheimer's Disease (AD) are associated with substantial declines in
episodic memory. However, there is still debate as to how two forms of episodic
memory - recollection and familiarity - are affected by healthy and pathological
aging. To address this issue we conducted a meta-analytic review of the effect
sizes reported in studies using remember/know (RK), receiver operating
characteristic (ROC) and process dissociation (PD) methods to examine
recollection and familiarity in healthy aging (25 published reports), aMCI (9
published reports), and AD (5 published reports). The results from the meta
analysis revealed that healthy aging is associated with moderate-to-large
recollection impairments. Familiarity was not impaired in studies using ROC or PD
methods but was impaired in studies that used the RK procedure. aMCI was
associated with large decreases in recollection whereas familiarity only tended
to show a decrease in studies with a patient sample comprised of both single
domain and multiple-domain aMCI patients. Lastly, AD was associated with large
decreases in both recollection and familiarity. The results are consistent with
neuroimaging evidence suggesting that the hippocampus is critical for
recollection whereas familiarity is dependent on the integrity of the surrounding
perirhinal cortex. Moreover, the results highlight the relevance of method
selection when examining aging, and suggest that familiarity deficits might be a
useful behavioral marker for identifying individuals that will develop dementia.
PMID- 25119309
TI - Acanthamoeba T4, T5 and T11 isolated from mineral water bottles in southern
Brazil.
AB - Acanthamoeba is a protist potential pathogen, capable of causing a blinding
keratitis in contact lens wearers and disseminated infection, leading to
granulomatous amebic encephalitis in immunocompromised individuals. This amoeba
is a ubiquitous organism that has been isolated from various domestic water
systems, such as cooling towers and hospital water networks. The objective of
this work was to investigate the presence of Acanthamoeba in mineral water
bottles marketed in Porto Alegre, southern Brazil. Positive samples were further
classified at the genotype level after sequencing the ASA.S1 region of 18S rDNA
gene. Six of the eight isolates belonged to T5 genotype, one to T4 genotype, and
one was T11. Several genotypes have been reported worldwide as causative of
pathologies in humans, including genotypes T4, T5 and T11. Overall, the
widespread distribution of potentially pathogenic Acanthamoeba strains in the
studied source demands more awareness within the public and health professionals,
because this pathogen is emerging as a risk for human health worldwide.
PMID- 25119311
TI - Common and rare variants in the exons and regulatory regions of osteoporosis
related genes improve osteoporotic fracture risk prediction.
AB - CONTEXT: Osteoporotic fracture risk is highly heritable, but genome-wide
association studies have explained only a small proportion of the heritability to
date. Genetic data may improve prediction of fracture risk in osteopenic subjects
and assist early intervention and management. OBJECTIVE: To detect common and
rare variants in coding and regulatory regions related to osteoporosis-related
traits, and to investigate whether genetic profiling improves the prediction of
fracture risk. DESIGN AND SETTING: This cross-sectional study was conducted in
three clinical units in Korea. PARTICIPANTS: Postmenopausal women with extreme
phenotypes (n = 982) were used for the discovery set, and 3895 participants were
used for the replication set. MAIN OUTCOME MEASURE: We performed targeted
resequencing of 198 genes. Genetic risk scores from common variants (GRS-C) and
from common and rare variants (GRS-T) were calculated. RESULTS: Nineteen common
variants in 17 genes (of the discovered 34 functional variants in 26 genes) and
31 rare variants in five genes (of the discovered 87 functional variants in 15
genes) were associated with one or more osteoporosis-related traits. Accuracy of
fracture risk classification was improved in the osteopenic patients by adding
GRS-C to fracture risk assessment models (6.8%; P < .001) and was further
improved by adding GRS-T (9.6%; P < .001). GRS-C improved classification accuracy
for vertebral and nonvertebral fractures by 7.3% (P = .005) and 3.0% (P = .091),
and GRS-T further improved accuracy by 10.2% (P < .001) and 4.9% (P = .008),
respectively. CONCLUSIONS: Our results suggest that both common and rare
functional variants may contribute to osteoporotic fracture and that adding
genetic profiling data to current models could improve the prediction of fracture
risk in an osteopenic individual.
PMID- 25119310
TI - Exercise-induced irisin secretion is independent of age or fitness level and
increased irisin may directly modulate muscle metabolism through AMPK activation.
AB - CONTEXT: Irisin has been proposed to be a myokine mediating the effect of
exercise on adipocyte browning. The physiology of irisin in humans is not
completely understood. OBJECTIVE: To study the physiology of irisin in healthy
individuals with different age and fitness levels and to explore the direct
effects of irisin on muscle metabolism. DESIGN, SETTING, AND SUBJECTS: Treadmill
exercise studies were conducted to measure circulating irisin at baseline and in
response to exercise among old and young, physically active and sedentary
individuals. Also, high- and moderate-intensity swimming was performed in
adolescent men and women to study the effect of exercise intensity and the time
course of irisin induction by acute bouts of exercise. Human myotubes were
treated with recombinant irisin, and the effect on gene expression, cell
signaling, and metabolism was examined. RESULTS: Baseline circulating irisin was
lower in old (vs young) and physically active (vs sedentary) subjects. Despite
differences in basal levels, the percentage increase of irisin by acute bouts of
exercise was not related to age or fitness level. The time course study revealed
that circulating irisin increased immediately after high-intensity interval
exercise and declined 1 hour thereafter. In vitro experiments showed that irisin
facilitates glucose and lipid metabolism in human muscle through AMP kinase
phosphorylation. CONCLUSIONS: Despite the differences in basal irisin levels,
exercise-induced irisin secretion is independent of age or fitness level.
Increased irisin can directly modulate muscle metabolism through AMP kinase
activation.
PMID- 25119312
TI - Changes in bone mineral density in newly diagnosed testicular cancer patients
after anticancer treatment.
AB - CONTEXT: Patients with germ cell tumors (GCTs) have an excellent prognosis but
are at risk for silent fractures. Data on bone mineral density (BMD) after
anticancer treatment are scarce. OBJECTIVE: The objective of the study was BMD
monitoring in GCT patients treated with or without chemotherapy. DESIGN: We
prospectively studied 63 newly diagnosed GCT patients with a median age of 33
years (range 16-70 y) within 3 months of unilateral orchidectomy. Twenty-seven
patients (42.9%) had no metastases. Thirty-six patients (57.1%) with metastatic
disease received combination chemotherapy. SETTING: This study was conducted at
the outpatient clinic of a single academic institution. INTERVENTIONS: We
performed dual-energy X-ray absorptiometry scans and collected blood samples on a
yearly basis, before and up to 5 years after anticancer treatment. MAIN OUTCOME
MEASURES: Changes in total hip and lumbar spine BMD, serum concentrations of
gonadal hormones, and bone turnover markers were measured. RESULTS: BMD remained
normal in stage I patients. In patients with metastatic disease, a significant
decrease in lumbar spine BMD (-1.52%; P = .004) and total hip BMD (-2.05%; P <
.0001) was observed 1 year after chemotherapy and remained stable thereafter for
up to 5 years. There was no significant relationship between the observed
decrease in BMD and gonadal status, vitamin D status, or cumulative dose of
cisplatin or (antiemetic) corticosteroids. CONCLUSIONS: Metastatic GCT survivors
demonstrate significant bone loss within the first year after curative
combination chemotherapy, with no recovery up to 5 years after anticancer
treatment. Whether this bone loss is associated with increased fracture risk and
whether this could be prevented by bone modifying treatment remains to be
established.
PMID- 25119313
TI - Ethnic differences in insulin sensitivity, beta-cell function, and hepatic
extraction between Japanese and Caucasians: a minimal model analysis.
AB - CONTEXT: Ethnic differences have previously been reported for type 2 diabetes.
OBJECTIVE: We aimed at assessing the potential differences between Caucasian and
Japanese subjects ranging from normal glucose tolerance (NGT) to impaired glucose
tolerance (IGT) and to type 2 diabetes. DESIGN: This was a cross-sectional study
with oral glucose tolerance tests to assess beta-cell function, hepatic insulin
extraction, and insulin sensitivity. PARTICIPANTS: PARTICIPANTS included 120
Japanese and 150 Caucasian subjects. MAIN OUTCOMES: Measures of beta-cell
function, hepatic extraction, and insulin sensitivity were assessed using C
peptide, glucose, and insulin minimal models. RESULTS: Basal beta-cell function
(Phi(b)) was lower in Japanese compared with Caucasians (P < .01). In subjects
with IGT, estimates of the dynamic (Phi(d)) and static (Phi(s)) beta-cell
responsiveness were significantly lower in the Japanese compared with Caucasians
(P < .05). In contrast, values of insulin action showed higher sensitivity in the
Japanese IGT subjects. Hepatic extraction was similar in NGT and IGT groups but
higher in Japanese type 2 diabetic subjects (P < .01). Despite differences in
insulin sensitivity, beta-cell function, and hepatic extraction, the disposition
indices were similar between the 2 ethnic groups at all glucose tolerance states.
Furthermore, the overall insulin sensitivity and beta-cell responsiveness for all
glucose tolerance states were similar in Japanese and Caucasians after accounting
for differences in body mass index. CONCLUSION: Our study provides evidence for a
similar ability of Japanese and Caucasians to compensate for increased insulin
resistance.
PMID- 25119314
TI - Aldosterone suppression on contralateral adrenal during adrenal vein sampling
does not predict blood pressure response after adrenalectomy.
AB - CONTEXT: Adrenal vein sampling (AVS) is the only reliable means to distinguish
between aldosterone-producing adenoma and bilateral adrenal hyperplasia, the two
most common subtypes of primary aldosteronism (PA). AVS protocols are not
standardized and vary widely between centers. OBJECTIVE: The objective of the
study was to retrospectively investigate whether the presence of contralateral
adrenal (CL) suppression of aldosterone secretion was associated with improved
postoperative outcomes in patients who underwent unilateral adrenalectomy for PA.
SETTING: The study was carried out in eight different referral centers in Italy,
Germany, and Japan. PATIENTS: From 585 consecutive AVS in patients with confirmed
PA, 234 procedures met the inclusion criteria and were used for the subsequent
analyses. RESULTS: Overall, 82% of patients displayed contralateral suppression.
This percentage was significantly higher in ACTH stimulated compared with basal
procedures (90% vs 77%). The CL ratio was inversely correlated with the
aldosterone level at diagnosis and, among AVS parameters, with the lateralization
index (P = .02 and P = .01, respectively). The absence of contralateral
suppression was not associated with a lower rate of response to adrenalectomy in
terms of both clinical and biochemical parameters, and patients with CL
suppression underwent a significantly larger reduction in the aldosterone levels
after adrenalectomy. CONCLUSIONS: For patients with lateralizing indices of
greater than 4 (which comprised the great majority of subjects in this study), CL
suppression should not be required to refer patients to adrenalectomy because it
is not associated with a larger blood pressure reduction after surgery and might
exclude patients from curative surgery.
PMID- 25119317
TI - On the chemical behavior of C60 hosting H2O and other isoelectronic neutral
molecules.
AB - The density functional theory (DFT) was used to investigate the chemical behavior
of C60 hosting neutral guest molecules (NGM). The deformed atoms in molecules
(DAM) allowed identifying the regions of electron density depletion and
accumulation. The studied NGM are CH4, NH3, H2O, and HF. Based on dipole moment
and polarizabilities analyses it is predicted that the NGM@C60 should be more
soluble in polar solvents than C60. The deformations on the surface electron
density of the fullerenes explain this finding, which might be relevant for
further applications of these systems. It was found that the intrinsic reactivity
of studied NGM@C60 is only moderately higher than that of C60. This trend is
supported by the global reactivity indexes and the frontier orbitals analyses.
The free radical scavenging activity of the studied systems, via single electron
transfer, was found to be strongly dependent on the chemical nature of the
reacting free radical. The presence of the studied NGM inside the C60 influences
only to some extent the reactivity of C60 toward free radicals. The distortion of
the electron density on the C60 cage, caused by the NGM, is directly related to
the electron withdrawing capacity of the later.
PMID- 25119316
TI - Lenti-GDNF gene therapy protects against Alzheimer's disease-like neuropathology
in 3xTg-AD mice and MC65 cells.
AB - AIMS: Glial cell-derived neurotrophic factor (GDNF) is emerging as a potent
neurotrophic factor with therapeutic potential against a range of
neurodegenerative conditions including Alzheimer's disease (AD). We assayed the
effects of GDNF treatment in AD experimental models through gene-therapy
procedures. METHODS: Recombinant lentiviral vectors were used to overexpress GDNF
gene in hippocampal astrocytes of 3xTg-AD mice in vivo, and also in the MC65
human neuroblastoma that conditionally overexpresses the 99-residue carboxyl
terminal (C99) fragment of the amyloid precursor protein. RESULTS: After 6 months
of overexpressing GDNF, 10-month-old 3xTg-AD mice showed preserved learning and
memory, while their counterparts transduced with a green fluorescent protein
vector showed cognitive loss. GDNF therapy did not significantly reduce amyloid
and tau pathology, but rather, induced a potent upregulation of brain-derived
neurotrophic factor that may act in concert with GDNF to protect neurons from
atrophy and degeneration. MC65 cells overexpressing GDNF showed an abolishment of
oxidative stress and cell death that was at least partially mediated by a reduced
presence of intracellular C99 and derived amyloid beta oligomers. CONCLUSIONS:
GDNF induced neuroprotection in the AD experimental models used. Lentiviral
vectors engineered to overexpress GDNF showed to be safe and effective, both as a
potential gene therapy and as a tool to uncover the mechanisms of GDNF
neuroprotection, including cross talk between astrocytes and neurons in the
injured brain.
PMID- 25119315
TI - Integrative analysis of GWASs, human protein interaction, and gene expression
identified gene modules associated with BMDs.
AB - CONTEXT: To date, few systems genetics studies in the bone field have been
performed. We designed our study from a systems-level perspective by integrating
genome-wide association studies (GWASs), human protein-protein interaction (PPI)
network, and gene expression to identify gene modules contributing to
osteoporosis risk. METHODS: First we searched for modules significantly enriched
with bone mineral density (BMD)-associated genes in human PPI network by using 2
large meta-analysis GWAS datasets through a dense module search algorithm. One
included 7 individual GWAS samples (Meta7). The other was from the Genetic
Factors for Osteoporosis Consortium (GEFOS2). One was assigned as a discovery
dataset and the other as an evaluation dataset, and vice versa. RESULTS: In
total, 42 modules and 129 modules were identified significantly in both Meta7 and
GEFOS2 datasets for femoral neck and spine BMD, respectively. There were 3340
modules identified for hip BMD only in Meta7. As candidate modules, they were
assessed for the biological relevance to BMD by gene set enrichment analysis in 2
expression profiles generated from circulating monocytes in subjects with low
versus high BMD values. Interestingly, there were 2 modules significantly
enriched in monocytes from the low BMD group in both gene expression datasets
(nominal P value <.05). Two modules had 16 nonredundant genes. Functional
enrichment analysis revealed that both modules were enriched for genes involved
in Wnt receptor signaling and osteoblast differentiation. CONCLUSION: We
highlighted 2 modules and novel genes playing important roles in the regulation
of bone mass, providing important clues for therapeutic approaches for
osteoporosis.
PMID- 25119318
TI - Quantum dynamics study of H + DBr and D + HBr reaction.
AB - Time-dependent quantum wave packet calculations have been performed for the H +
DBr and D + HBr reaction using the recent diabatic potential energy surfaces.
Reaction probabilities, integral cross sections, and rate constants are obtained.
The results show that the isotopic effects have an influence on the nonadiabatic
effect which is generally inversely proportional to the atom mass. The calculated
rate constants are in good overall agreement with experimental values, indicating
that the ab initio surfaces are accurate to describe the isotopic effects.
PMID- 25119319
TI - A computational study of hydrogen bonds in intermolecular systems of high
complexity: arachno-pentaborane(11)...Y with Y = O2 and N 2.
AB - The interactions of arachno-B(5)H(11) with N(2) and O(2) were theoretically
studied. In the B(5)H(11)...N(2) and B(5)H(11)...O(2) complexes, the terminal
hydrogens of B(5)H(11) work as electron donors whereas the bridge ones as
electron acceptors. The optimized structures and the corresponding harmonic
vibration spectra were investigated through the MP2/aug-cc-pVDZ level of theory.
In order to characterize the hydrogen bonds, the topological calculations
inherent to the QTAIM protocol and MEP analysis were carried out. The NBO
analyses were useful in the interpretation of the red-shifts and blue-shifts on
the stretch frequencies of the proton donors, of course in agreement with the
Bent rule for the chemical bonding as well as by the conceptions of
hyperconjugation or hybridization.
PMID- 25119322
TI - No lost opportunities in the emergency department.
PMID- 25119321
TI - UK mental health provision is not up to scratch.
PMID- 25119323
TI - Integrating psychological screening into reviews of patients with COPD.
AB - BACKGROUND: People with chronic obstructive pulmonary disease (COPD) have a high
prevalence of anxiety and depression, which can have an impact on their symptoms
and the way they manage their condition. Intervention that takes psychological
distress into account may lead to better outcomes than simple advice-giving. AIM:
To explore the feasibility of integrating psychological screening and
intervention into nurse-led reviews of patients with COPD. METHOD: Nurses were
given training on a pathway developed for patients with COPD. This included
screening for depression and anxiety and assessing their severity; providing self
management education by means of a motivational approach; and offering pulmonary
rehabilitation. RESULTS: The nurses' level of confidence increased following
training. Patients were accepting of the screening process and felt more able and
motivated to manage their condition after the intervention. Eleven of the 35
patients that took part in the study period had evidence of anxiety and/or
depression. Out of a total of 16 patients eligible for pulmonary rehabilitation,
12 agreed to referral. Of these, three patients were seen by their GP, one was
started on antidepressants, and one was referred to the psychology service.
CONCLUSION: Training practice nurses to screen for depression and anxiety, and to
offer self-management education using a motivational interviewing approach,
increased the reported capability and motivation of patients with COPD to manage
their condition. It may also improve the uptake of pulmonary rehabilitation. Use
of this pathway does not place a burden on other care providers or greatly
increase prescribing costs.
PMID- 25119320
TI - Optimization of dual-energy subtraction chest radiography by use of a direct
conversion flat-panel detector system.
AB - We aimed to optimize the exposure conditions in the acquisition of soft-tissue
images using dual-energy subtraction chest radiography with a direct-conversion
flat-panel detector system. Two separate chest images were acquired at high- and
low-energy exposures with standard or thick chest phantoms. The high-energy
exposure was fixed at 120 kVp with the use of an auto-exposure control technique.
For the low-energy exposure, the tube voltages and entrance surface doses ranged
40-80 kVp and 20-100 % of the dose required for high-energy exposure,
respectively. Further, a repetitive processing algorithm was used for reduction
of the image noise generated by the subtraction process. Seven radiology
technicians ranked soft-tissue images, and these results were analyzed using the
normalized-rank method. Images acquired at 60 kVp were of acceptable quality
regardless of the entrance surface dose and phantom size. Using a repetitive
processing algorithm, the minimum acceptable doses were reduced from 75 to 40 %
for the standard phantom and to 50 % for the thick phantom. We determined that
the optimum low-energy exposure was 60 kVp at 50 % of the dose required for the
high-energy exposure. This allowed the simultaneous acquisition of standard
radiographs and soft-tissue images at 1.5 times the dose required for a standard
radiograph, which is significantly lower than the values reported previously.
PMID- 25119324
TI - Arterialised earlobe capillary blood gases in the COPD population.
AB - Arterialised ear lobe capillary blood (ELCB) gas sampling is a widely used
clinical procedure undertaken across both primary and secondary care settings.
The prevalence of this sampling method has grown among health professionals,
coupled with a growing demand for domiciliary oxygen therapy in the UK, in
particular for those who have chronic obstructive pulmonary disease (COPD).
Research studies supporting arterialised ELCB gas sampling show inconsistencies
in technique, and a survey of respiratory nurses' current practice demonstrated
wider inconsistencies. In the absence of national clinical guidelines to direct
this practice, and an acknowledged and accepted under-calculation of partial
pressure of oxygen, this article investigates the sampling method used to obtain
arterialised ELCB gas sampling and consequently questions its reliability in
practice.
PMID- 25119325
TI - Spiritual coping of older persons in Malta and Australia (part 2).
AB - Part I presented the research methodology and the quantitative findings of this
descriptive sequential explanatory study. Part 2 will discuss the qualitative
findings that explain the impact of the use of spiritual coping strategies on
institutionalised older persons. Participants were recruited from six
institutions in Malta and Australia: four private homes (two in Australia, n=30;
two in Malta, n=43) and two state residences in Malta (n=64). The residents
(n=137; 103 women, 34 men), aged 72.8 years (mean) were all Roman Catholics,
mobile and with a minimal residence of 6 months. The quantitative data (phase I)
were collected by the Maltese version of the Spiritual Coping scale (SCS) (
Baldacchino and Buhagiar, 2003 ) while the qualitative data were collected
through audiotaped face-to-face interviews (n=42) (phase II) and three focus
groups (n=23) (phase III). The qualitative data generated three main themes,
namely: self-empowerment through connectedness with God, self, others and nature;
belongingness to the residence; and the finding of meaning and purpose in life or
the perceived afterlife. Recommendations were made for integration of
spirituality into nursing education and clinical practice; more frequent
participation in the socio-religious activities at ward level; self-awareness
exercises and support groups; and further crosscultural longitudinal studies.
PMID- 25119326
TI - Importance of being flexible in nurse education.
PMID- 25119327
TI - Decontamination methods for flexible nasal endoscopes.
AB - A national survey was carried out to investigate the current UK practice for
decontaminating flexible nasal endoscopes. A postal questionnaire was sent to
Sisters in Charge of 200 ear, nose and throat (ENT) outpatient departments in the
UK, with an overall response rate of 60.5%. Decontamination with chlorine dioxide
wipes was the most favoured method, used in 58% of the hospitals that
participated in this survey. Automated machines were also used in many places
(34%). Only a few hospitals used flexible sheaths (7%). Many departments do not
use a separate protocol for high-risk patients.
PMID- 25119328
TI - Understanding the concept of the key worker: do focus groups help?
AB - The concept of the 'key-worker role' within paediatric haematology and oncology
services is recognised in the UK through inclusion in published policies and
guidance. Such guidance originates from both statutory and voluntary sector
organisations. Within the policy direction itself, references are made to both
'designated' and 'non-designated' key workers, and there remains ongoing
confusion within the professional field about the exact nature of the process of
'key-working' and how this should operate. This confusion therefore also exists
for parents, carers and service users. The project described here aimed to
examine the concept of the key-worker role through consultation with users as
part of local service development. Focus group discussion was identified as the
methodology of choice. Careful planning and delivery ensured that meaningful data
emerged. Active participation by those attending the focus group discussion was
observed. The focus group was in two sessions, both of which were digitally
recorded and transcribed, with contemporaneous notes taken. These were subjected
to thematic analysis and clear themes emerged regarding the importance of
terminology, communication, skill mix and the use of technology. This local
project achieved greater clarity about how to develop the key-worker role to best
meet the needs of users through highlighting the need to include both the key
worker role, and the process of key-working. It is concluded that the use of
focus groups is both a valid and valuable mechanism of consultation, as user
consultation regarding service design and evaluation of care delivered is high on
the wider agenda of the NHS.
PMID- 25119329
TI - New registration process for overseas nurses.
PMID- 25119330
TI - The Mental Capacity Act 2005: riding the storm of criticism.
PMID- 25119331
TI - Written communication: from staff nurse to nurse consultant. Part 1: core
principles.
PMID- 25119332
TI - We should engage with the Code.
PMID- 25119333
TI - Dosimetric evaluation of hybrid brass/stainless-steel apertures for proton
therapy.
AB - In passive scattering proton therapy, patient specific collimators (apertures)
are used to laterally shape the proton beam, and compensators are employed to
distally conform proton dose to the target. Brass is a commonly used material for
apertures and recently a hybrid brass/stainless-steel (BR/SST) aperture design
has been introduced to reduce treatment cost without clinical flow change. We
measured stopping power and leakage dose for apertures made of stainless steel
and brass in the Proton Therapy system. The linear stopping power ratios for
stainless steel (type 304) and brass to water were calculated to be 5.46 and
5.51, respectively. Measured stopping power ratios of SST and BR were 5.51 +/-
0.04 and 5.56 +/- 0.08, respectively, which agrees with the calculated values
within 1%. Leakage dose on the downstream surface of two slabs of O18 cm
stainless steel apertures (total thickness of 6.5 cm) for the maximum available
proton energy (235 MeV) was 1.283% +/- 0.004% of the prescription dose, and was
smaller compared to the 1.358% +/- 0.005% leakage dose measured for existing
brass apertures of identical physical dimensions. Therefore, the existing beam
range limits for brass aperture slabs used at our institution with safety margin
allowances for material composition and delivered beam range uncertainties can be
safely applied for the new BR/SST aperture design. Potential range differences in
the brass and stainless steel interface regions of the hybrid design were further
investigated using EBT3 GafChromic film. Film dosimetry revealed no discernible
range variations across the brass and stainless steel interface regions. Neutron
dose to the patient from brass and stainless steel apertures was simulated using
the Monte Carlo method. The results indicate that stainless steel produces
similar patient neutron dose compared to brass. Material activation dose rates of
stainless steel were measured over a period of 7 d after irradiation. The
measurements showed that the proton induced SST activity is initially lower and
also decays at a faster rate than that induced in brass, therefore requires no
changes in radiation protection requirements on material disposals. The Monte
Carlo simulation confirmed higher initial activity of brass than stainless steel
shortly after irradiation. The hybrid BR/SST aperture design is suitable for
clinical use to replace the current brass apertures for all clinically used
proton ranges. The existing aperture disposal procedures also satisfy radiation
protection requirements for the new hybrid type apertures.
PMID- 25119334
TI - Transplantation of neural stem cells clonally derived from embryonic stem cells
promotes recovery after murine spinal cord injury.
AB - The pathology of spinal cord injury (SCI) makes it appropriate for cell-based
therapies. Treatments using neural stem cells (NSCs) in animal models of SCI have
shown positive outcomes, although uncertainty remains regarding the optimal cell
source. Pluripotent cell sources such as embryonic stem cells (ESCs) provide a
limitless supply of therapeutic cells. NSCs derived using embryoid bodies (EB)
from ESCs have shown tumorigenic potential. Clonal neurosphere generation is an
alternative method to generate safer and more clinically relevant NSCs without
the use of an EB stage for use in cell-based therapies. We generated clonally
derived definitive NSCs (dNSCs) from ESC. These cells were transplanted into a
mouse thoracic SCI model. Embryonic stem cell-derived definitive neural stem cell
(ES-dNSC)-transplanted mice were compared with controls using behavioral measures
and histopathological analysis of tissue. In addition, the role of remyelination
in injury recovery was investigated using transmission electron microscopy. The
SCI group that received ES-dNSC transplantation showed significant improvements
in locomotor function compared with controls in open field and gait analysis. The
cell treatment group had a significant enhancement of spared neural tissue.
Immunohistological assessments showed that dNSCs differentiated primarily to
oligodendrocytes. These cells were shown to express myelin basic protein,
associate with axons, and support nodal architecture as well as display proper
compact, multilayer myelination in electron microscopic analysis. This study
provides strong evidence that dNSCs clonally derived from pluripotent cells using
the default pathway of neuralization improve motor function after SCI and enhance
sparing of neural tissue, while remaining safe and clinically relevant.
PMID- 25119335
TI - Elaidic, vaccenic, and rumenic acid status during pregnancy: association with
maternal plasmatic LC-PUFAs and atopic manifestations in infants.
AB - BACKGROUND: Few studies have explored whether fetal exposure to trans fatty acids
(TFAs) influences the inception of atopic diseases. The aim of this study was to
investigate the relationship between the concentration of specific TFAs (elaidic,
vaccenic, and rumenic acids) in maternal plasma and the risk of developing atopic
manifestations in the first year of life. METHODS: A subsample from a population
based pregnancy cohort of the INMA Project was analyzed. Maternal intake of fatty
acids was assessed by a food-frequency questionnaire (75.5% of the cohort). TFAs
and n-3 and n-6 long-chain polyunsaturated fatty acids were measured in samples
of plasmatic phospholipids at 12 wk of pregnancy. Information regarding eczema
and wheeze in offspring was obtained through questionnaires at ages 6 and 14 mo.
RESULTS: Elaidic acid correlated negatively with n-3 long-chain polyunsaturated
fatty acids (total, eicosapentaenoic acid, and docosahexaenoic acid), and rumenic
acid positively with both n-3 and n-6 long-chain polyunsaturated fatty acids in
maternal plasma. Neither of these two fatty acids was associated with the risk of
atopic eczema or wheeze in offspring in the first year of life. However, a higher
vaccenic acid level was found to be linked to a lower risk of atopic eczema.
CONCLUSION: High vaccenic acid concentrations in maternal plasma may protect
offspring against atopic eczema in infancy.
PMID- 25119337
TI - MBL2 gene polymorphisms increase the risk of adverse neurological outcome in
preterm infants: a preliminary prospective study.
AB - BACKGROUND: As described in animal models, the lectin-complement pathway is
central to the propagation of ischemia-reperfusion injuries in many tissues,
including the brain. Similarly, it might affect the genesis of brain damage in
preterm infants. MBL2 gene single-nucleotide polymorphisms (SNPs), regulating
mannose-binding lectin (MBL) serum levels, could predict the risk of adverse
neurological outcome in these infants. METHODS: To evaluate the association
between SNPs of the MBL2 gene and long-term neurological outcomes in preterm
infants, 75 infants (gestational age (GA) <= 32 wk) were observed in a
prospective longitudinal study and assessed by clinical and instrumental exams at
12 and 24 mo of corrected age (CA). They were genotyped for the promoter
polymorphism -221 and for the exon-1 variant alleles (at codons 52, 54, and 57)
of the MBL2 gene. RESULTS: The MBL2 exon-1 OO genotype was more frequent in
children with an adverse neurological outcome (5/35; 7%) than in controls (0/40;
0%), P = 0.045. The risk of intraventricular hemorrhage in carriers of the
genotype OO was marked, without reaching statistical significance (odds ratio:
8.67; 95% confidence interval: 0.87-86.06; P = 0.07). CONCLUSION: Preterm infants
who are carriers of MBL2 exon-1 OO genotype are exposed to an increased risk of
adverse neurological outcomes.
PMID- 25119336
TI - One size will never fit all: the future of research in pediatric transfusion
medicine.
AB - There is concern at the National Heart, Lung, and Blood Institute (NHLBI) and
among transfusion medicine specialists regarding the small number of
investigators and studies in the field of pediatric transfusion medicine (PTM).
Accordingly, the objective of this article is to provide a snapshot of the
clinical and translational PTM research considered to be of high priority by
pediatricians, neonatologists, and transfusion medicine specialists. Included is
a targeted review of three research areas of importance: (i) transfusion
strategies, (ii) short- and long-term clinical consequences, and (iii)
transfusion-transmitted infectious diseases. The recommendations by PTM and
transfusion medicine specialists represent opportunities and innovative
strategies to execute translational research, observational studies, and clinical
trials of high relevance to PTM. With the explosion of new biomedical knowledge
and increasingly sophisticated methodologies over the past decade, this is an
exciting time to consider transfusion medicine as a paradigm for addressing
questions related to fields such as cell biology, immunology, neurodevelopment,
outcomes research, and many others. Increased awareness of PTM as an important,
fertile field and the promotion of accompanying opportunities will help establish
PTM as a viable career option and advance basic and clinical investigation to
improve the health and wellbeing of children.
PMID- 25119338
TI - Reduced sensitivity of the renal vasculature to angiotensin II in young rats: the
role of the angiotensin type 2 receptor.
AB - BACKGROUND: The angiotensin type-2 receptor (AT2R) opposes the vasoconstrictor
actions of angiotensin II (AngII) mediated through the angiotensin type-1
receptor (AT1R). Renal AT2R levels are high during fetal life, but decrease
significantly during postnatal maturation. To provide insight into the functional
role of the AT2R in the kidney during postnatal development, we investigated the
effects of AT2R antagonism on cardiovascular responses to AngII in young and
adult male rats. METHODS: In anesthetized 3- and 6-wk-old male Sprague-Dawley
rats, mean arterial pressure (MAP) and renal blood flow (RBF) were measured in
response to AngII in the presence of vehicle treatment or AT2R blockade with
PD123319. RESULTS: The pressor effect of AngII and associated reduction in RBF
were significantly less in 3-wk- than 6-wk-old rats. AT2R blockade potentiated
the reduction in RBF in response to AngII in 3-wk-old rats only. CONCLUSION: In
young rats, the AT2R modulates the response to AngII, blunting renal
vasoconstriction. This effect is attenuated with age in association with a
developmental reduction in renal AT2R expression. These findings may have
implications for the development of novel therapies that target the renin
angiotensin system for the improvement of renal function in term and, in
particular, preterm infants.
PMID- 25119339
TI - Effects of iron supplements and perinatal factors on fetal hemoglobin
disappearance in LBW infants.
AB - BACKGROUND: The homeostatic mechanisms of iron metabolism and erythropoiesis in
infants are unclear. Infants synthesize both fetal hemoglobin (HbF) and adult
hemoglobin (HbA), and it is not known how the hemoglobin switch is regulated. We
hypothesized that iron supplements to infants affect the disappearance of HbF.
METHODS: We randomized 285 low-birth-weight infants (2,000-2,500 g) into three
intervention groups receiving 0, 1, or 2 mg/kg/d of iron supplements from 6 wk to
6 mo of age. In the present secondary analysis, we analyzed iron status, total
hemoglobin (Hb), and HbF fraction at 6 wk, 12 wk, and at 6 mo and calculated
absolute levels of HbF. RESULTS: We observed dose-dependent increased levels of
Hb in iron-supplemented groups at 6 mo of age. However, for absolute HbF
concentration, there was no similar effect of intervention. Mean (SD) HbF was
81.2 (16.8), 37.0 (13.8), and 8.1 (5.6) g/l at 6 wk, 12 wk, and 6 mo,
respectively, similar in all groups. In linear regression analyses,
postconceptional age turned out as the major predictor of HbF, independent of
gestational age at birth. CONCLUSION: Our hypothesis was rejected. Instead, we
confirmed a close correlation to postconceptional age, supporting a genetically
programmed switch, insensitive to most environmental factors including birth.
PMID- 25119340
TI - Combination of intrauterine growth restriction and a high-fat diet impairs
cholesterol elimination in rats.
AB - BACKGROUND: Intrauterine growth restriction (IUGR) increases the risk of adult
onset hypercholesterolemia. High-fat diet (HFD) consumption potentiates IUGR
induced increased cholesterol. Cholesterol is converted to bile acids by Cyp7a1
in preparation for excretion. We hypothesized that IUGR rats fed a HFD will have
increased cholesterol, decreased Cyp7a1 protein levels, and decreased bile acids
compared to control rats fed a HFD. METHODS: At day 21, IUGR and control pups
were placed on one of three diets: a regular chow or one of two HFDs containing
1% or 2% cholesterol. Cholesterol levels and hepatic Cyp7a1 protein levels were
quantified a postnatal week 28. RESULTS: Both HFDs increased serum cholesterol
levels in control rats, and HFD fed IUGR rats had further increased serum
cholesterol up to 35-fold. Both HFDs increased hepatic cholesterol levels, and
IUGR further increased hepatic cholesterol levels up to fivefold. IUGR decreased
hepatic Cyp7a1 protein up to 75%, and hepatic bile acids up to 54%. CONCLUSION:
IUGR increased cholesterol and bile acids and decreased Cyp7a1 protein in rats
fed a HFD without changing food intake. These findings suggest that IUGR
increases the vulnerability of HFD fed rats to hypercholesterolemia via decreased
cholesterol conversion to bile acids.
PMID- 25119342
TI - Psychometric Evaluation of the Wijma Delivery Expectancy/Experience Questionnaire
Version B.
AB - Examining the fear of delivery after childbirth is important. The authors' aim is
to examine the overall psychometric quality of the Wijma Delivery
Expectancy/Experience Questionnaire version B. Reliability and validity of the
instrument were evaluated via reliability analysis, exploratory and confirmatory
factor analyses, and multidimensional subscore estimation. A six-factor model was
proposed to explain instrument results. Factors included concerns about labor
pain, lack of positive behaviors, loneliness, lack of positive feelings, concerns
about childbirth, and concerns about the baby. Researchers provide psychometric
evidence about the quality of the questionnaire to measure fear of delivery after
childbirth.
PMID- 25119341
TI - Bystander activation and anti-tumor effects of CD8+ T cells following Interleukin
2 based immunotherapy is independent of CD4+ T cell help.
AB - We have previously demonstrated that immunotherapy combining agonistic anti-CD40
and IL-2 (IT) results in synergistic anti-tumor effects. IT induces expansion of
highly cytolytic, antigen-independent "bystander-activated" (CD8(+)CD44high) T
cells displaying a CD25(-)NKG2D(+) phenotype in a cytokine dependent manner,
which were responsible for the anti-tumor effects. While much attention has
focused on CD4(+) T cell help for antigen-specific CD8(+) T cell expansion,
little is known regarding the role of CD4(+) T cells in antigen-nonspecific
bystander-memory CD8(+) T cell expansion. Utilizing CD4 deficient mouse models,
we observed a significant expansion of bystander-memory T cells following IT
which was similar to the non-CD4 depleted mice. Expanded bystander-memory CD8(+)
T cells upregulated PD-1 in the absence of CD4(+) T cells which has been
published as a hallmark of exhaustion and dysfunction in helpless CD8(+) T cells.
Interestingly, compared to CD8(+) T cells from CD4 replete hosts, these bystander
expanded cells displayed comparable (or enhanced) cytokine production, lytic
ability, and in vivo anti-tumor effects suggesting no functional impairment or
exhaustion and were enriched in an effector phenotype. There was no acceleration
of the post-IT contraction phase of the bystander memory CD8(+) response in CD4
depleted mice. The response was independent of IL-21 signaling. These results
suggest that, in contrast to antigen-specific CD8(+) T cell expansion, CD4(+) T
cell help is not necessary for expansion and activation of antigen-nonspecific
bystander-memory CD8(+) T cells following IT, but may play a role in regulating
conversion of these cells from a central memory to effector phenotype.
Additionally, the expression of PD-1 in this model appears to be a marker of
effector function and not exhaustion.
PMID- 25119344
TI - Response to Ansell et al. "Non-vitamin K antagonist oral anticoagulants (NOACs):
no longer new or novel". (Thromb Haemost 2014; 112: 841).
PMID- 25119345
TI - Site-specific immobilization of recombinant antibody fragments through material
binding peptides for the sensitive detection of antigens in enzyme immunoassays.
AB - The immobilization of an antibody is one of the key technologies that are used to
enhance the sensitivity and efficiency of the detection of target molecules in
immunodiagnosis and immunoseparation. Recombinant antibody fragments such as VHH,
scFv and Fabs produced by microorganisms are the next generation of ligand
antibodies as an alternative to conventional whole Abs due to a smaller size and
the possibility of site-directed immobilization with uniform orientation and
higher antigen-binding activity in the adsorptive state. For the achievement of
site-directed immobilization, affinity peptides for a certain ligand molecule or
solid support must be introduced to the recombinant antibody fragments. In this
mini-review, immobilization technologies for the whole antibodies (whole Abs) and
recombinant antibody fragments onto the surfaces of plastics are introduced. In
particular, the focus here is on immobilization technologies of recombinant
antibody fragments utilizing affinity peptide tags, which possesses strong
binding affinity towards the ligand molecules. Furthermore, I introduced the
material-binding peptides that are capable of direct recognition of the target
materials. Preparation and immobilization strategies for recombinant antibody
fragments linked to material-binding peptides (polystyrene-binding peptides (PS
tags) and poly (methyl methacrylate)-binding peptide (PMMA-tag)) are the focus
here, and are based on the enhancement of sensitivity and a reduction in the
production costs of ligand antibodies. This article is part of a Special Issue
entitled: Recent advances in molecular engineering of antibody.
PMID- 25119343
TI - [Generalized anxiety disorder].
AB - Generalized anxiety disorder (GAD) is a prevalent mental condition with
substantial impact on psychosocial functioning and quality of life. There is also
an increased risk of comorbidity with several other mental and somatic diseases.
Clinical symptomatology is characterized by excessive and uncontrollable worrying
about distinct issues of daily living which is frequently associated with somatic
symptoms of stress and anxiety. Neurobiological and psychological research
provide evidence for alterations in (para) limbic areas, a disturbed
monoaminergic transmission as well as for dysfunctional learning in the
pathogenesis of GAD. Therefore, second generation antidepressants, such as
selective serotonin reuptake inhibitors (SSRI), selective serotonin
norepinephrine reuptake inhibitors (SSNRI), the calcium channel modulator
pregabalin and cognitive behavioral therapy (CBT) are the first choice treatment
options. Depending on symptom severity, patient preference and availability, both
medication and CBT can be applied as monotherapy or in combination.
PMID- 25119346
TI - Endovascular repair of arterial iliac vessel wall lesions with a self-expandable
nitinol stent graft system.
AB - OBJECTIVE: To assess the therapeutic outcome after endovascular repair of iliac
arterial lesions (IALs) using a self-expandable Nitinol stent graft system.
METHODS: Between July 2006 and March 2013, 16 patients (13 males, mean age: 68
years) with a self-expandable Nitinol stent graft. A total of 19 lesions were
treated: nine true aneurysms, two anastomotic aneurysms, two dissections, one
arteriovenous fistula, two type 1B endoleaks after endovascular aneurysm repair,
one pseudoaneurysm, and two perforations after angioplasty. Pre-, intra-, and
postinterventional imaging studies and the medical records were analyzed for
technical and clinical success and postinterventional complications. RESULTS: The
primary technical and clinical success rate was 81.3% (13/16 patients) and 75.0%
(12/16), respectively. Two patients had technical failure due to persistent type
1A endoleak and another patient due to acute stent graft thrombosis. One patient
showed severe stent graft kinking on the first postinterventional day. In two
patients, a second intervention was performed. The secondary technical and
clinical success rate was 87.5% (14/16) and 93.8% (15/16). The minor complication
rate was 6.3% (patient with painful hematoma at the access site). The major
complication rate was 6.3% (patient with ipsilateral deep vein thrombosis).
During median follow-up of 22.4 months, an infection of the aneurysm sac in one
patient and a stent graft thrombosis in another patient were observed.
CONCLUSION: Endovascular repair of various IALs with a self-expandable Nitinol
stent graft is safe and effective.
PMID- 25119348
TI - The parasitic fauna of the European bison (Bison bonasus) (Linnaeus, 1758) and
their impact on the conservation. Part 1. The summarising list of parasites
noted.
AB - During the current century, 88 species of parasites have been recorded in Bison
bonasus. These are 22 species of protozoa (Trypanosoma wrublewskii, T. theileri,
Giardia sp., Sarcocystis cruzi, S. hirsuta, S. hominis, S. fusiformis, Neospora
caninum, Toxoplasma gondii, Cryptosporidium sp., Eimeria cylindrica, E.
subspherica, E. bovis, E. zuernii, E. canadensis, E. ellipsoidalis, E.
alabamensis, E. bukidnonensis, E. auburnensis, E. pellita, E. brasiliensis,
Babesia divergens), 4 trematodes species (Dicrocoelium dendriticum, Fasciola
hepatica, Parafasciolopsis fasciolaemorpha, Paramphistomum cervi), 4 cestodes
species (Taenia hydatigena larvae, Moniezia benedeni, M. expansa, Moniezia sp.),
43 nematodes species (Bunostomum trigonocephalum, B. phlebotomum, Chabertia
ovina, Oesophagostomum radiatum, O. venulosum, Dictyocaulus filaria, D.viviparus,
Nematodirella alcidis, Nematodirus europaeus, N. helvetianus, N. roscidus, N.
filicollis, N. spathiger, Cooperia oncophora, C. pectinata, C. punctata, C.
surnabada, Haemonchus contortus, Mazamastrongylus dagestanicus, Ostertagia
lyrata, O. ostertagi, O. antipini, O. leptospicularis, O. kolchida, O.
circumcincta, O. trifurcata, Spiculopteragia boehmi, S. mathevossiani, S.
asymmetrica, Trichostrongylus axei, T. askivali, T. capricola, T. vitrinus,
Ashworthius sidemi, Onchocerca lienalis, O. gutturosa, Setaria labiatopapillosa,
Gongylonema pulchrum, Thelazia gulosa, T. skrjabini, T. rhodesi, Aonchotheca
bilobata, Trichuris ovis), 7 mites (Demodex bisonianus, D. bovis, Demodex sp.,
Chorioptes bovis, Psoroptes equi, P. ovis, Sarcoptes scabiei), 4 Ixodidae ticks
(Ixodes ricinus, I. persulcatus, I. hexagonus, Dermacentor reticulatus), 1
Mallophaga species (Bisonicola sedecimdecembrii), 1 Anoplura (Haematopinus
eurysternus), and 2 Hippoboscidae flies (Lipoptena cervi, Melophagus ovinus).
There are few monoxenous parasites, many typical for cattle and many newly
acquired from Cervidae.
PMID- 25119347
TI - Artificially constructed quorum-sensing circuits are used for subtle control of
bacterial population density.
AB - Vibrio fischeri is a typical quorum-sensing bacterium for which lux box, luxR,
and luxI have been identified as the key elements involved in quorum sensing. To
decode the quorum-sensing mechanism, an artificially constructed cell-cell
communication system has been built. In brief, the system expresses several
programmed cell-death BioBricks and quorum-sensing genes driven by the promoters
lux pR and PlacO-1 in Escherichia coli cells. Their transformation and expression
was confirmed by gel electrophoresis and sequencing. To evaluate its performance,
viable cell numbers at various time periods were investigated. Our results showed
that bacteria expressing killer proteins corresponding to ribosome binding site
efficiency of 0.07, 0.3, 0.6, or 1.0 successfully sensed each other in a
population-dependent manner and communicated with each other to subtly control
their population density. This was also validated using a proposed simple
mathematical model.
PMID- 25119349
TI - The parasitic fauna of the European bison (Bison bonasus) (Linnaeus, 1758) and
their impact on the conservation. Part 2. The structure and changes over time.
AB - During the last century the recorded parasite fauna of Bison bonasus includes 88
species. These are 22 species of protozoa, 4 trematode species, 4 cestode
species, 43 nematode species, 7 mites, 4 Ixodidae ticks, 1 Mallophaga species, 1
Anoplura, and 2 Hippoboscidae flies. There are few monoxenous parasites, the
majority of parasites are typical for other Bovidae and Cervidae species and many
are newly acquired from Cervidae. This is an evident increased trend in the
parasite species richness, in both the prevalence and intensity of infections,
which is associated with the bison population size, host status (captive breeding
or free-ranging) and the possibility of contact with other ruminant species. In
light of the changes to parasite species richness during the last decades,
special emphasis shall be given to new parasite species reported in European
bison, their pathogenicity and potential implications for conservation.
PMID- 25119350
TI - Larval helminths in the invasive American brine shrimp Artemia franciscana
throughout its annual cycle.
AB - One of the best examples of rapid displacement of native species by an invader is
the eradication of native Artemia salina and A. parthenogenetica in the
Mediterranean by the introduced American A. franciscana. Previous studies based
on sampling from limited time periods suggest that the success of the American
species as a competitor may be due partly to different parasite burden, since
native Artemia spp. have high cestode infection rates regulating their density.
The aim of this study is to test the hypothesis that the helminth infection in A.
franciscana in its invasive range is low throughout its annual life cycle.
Samples of A. franciscana were collected every second month from La Tapa saltern
(Andalusia) during one year. Five helminth species were recorded: cestodes
Flamingolepis liguloides, F. flamingo, Gynandrotaenia stammeri (all flamingo
parasites), Eurycestus avoceti (a shorebird parasite) and larval spirurids of the
Acuariinae (the first record of nematodes in Artemia). The overall infection rate
was low, with total prevalence 5.9% and prevalence of individual parasite species
between 0.2 and 3.2%. The mean abundance of helminths was 0.005-0.155 (av.
0.068), 5-13 times lower than in native congeners. Waterbird counts indicate that
the low infection rates cannot be explained by lack of definitive hosts. The
results are consistent with the hypothesis that helminths have no regulating
effect on the invasive brine shrimp in the Mediterranean. The replacement of the
native populations by the invader can be partially explained by a competition
mediated by parasites/predators through a differential impact on host fitness.
PMID- 25119351
TI - Feline patent Toxoplasma-like coccidiosis among feral cats (Felis catus) in Doha
city, Qatar and its immediate surroundings.
AB - Doha city has a high feral cat population and studies of hospital records in Doha
have shown that human toxoplasmosis also occurs. Clearly, there is a need to
understand the role of cats as vectors of human toxoplasmosis in the city and as
a first step we assessed the extent of patent Toxoplasma-like coccidial
infections among feral cats. Oocysts in cat faeces were detected between June
2008 and April 2010, from a range of locations radiating out of the city centre
in concentric semi circular/elliptic rings and by north, west and south divisions
within each of the rings. In total 4,652 cats were sampled and overall prevalence
of oocysts was 9.1%. Prevalence was 10.1% in the first summer, and then dropped
to 8.4% in the following winter and further to 6.8% in the next summer before
rising to 10.6% in the final winter of the study; this interaction between annual
period and season was significant. There were also significant changes in
prevalence across each of the consecutive months of the study, but no clear
pattern was evident. Prevalence did not vary significantly by city sector and
there was no difference in prevalence between the host sexes. We conclude
therefore, that despite minor and significant perturbations, the prevalence of
patent Toxoplasma-like coccidial infections among cats in Doha is remarkably
stable throughout the year, across years and spatially within the city's
districts.
PMID- 25119352
TI - Metazoan endoparasites diversity of Pseudoplatystoma corruscans (Siluriformes:
Pimelodidae) as an indicator of environmental alterations on a tropical aquatic
system.
AB - The aim of the present study was to detect the alterations of Pseudoplatystoma
corruscans parasite infracommunity structure, after the construction of the Porto
Primavera dam on the high Parana River floodplain. The execution of this research
was based on 119 host specimens collected between March 2011 and September 2012,
and the results were compared to studies performed on periods before the
reservoir's construction, when 110 fishes were collected between March 1992 and
February 1993. Five parasite species still remain on the environment, despite the
environmental modifications: Choanoscolex abscissus, Spasskyelina spinulifera,
Nomimoscolex pertierrae, Harriscolex kaparari and Contracaecum sp 2. The Berger
Parker dominance index, calculated to the parasite fauna of 1992, did not show
the dominance of any species, while, on the present days, this same index accused
the dominance of Nomimoscolex pertierrae (49%) and Choanoscolex abscissus (50%).
The present study reports the disappearance of Megathylacus travassosi,
Contracaecum sp. 1, Contracaecum sp. 3, Procamallanus (Spirocamallanus) sp. and
Cucullanus pseudoplatystomae, suggesting the possibility of a local extinction or
a host switch of these species. It has also been registered an Acanthocephala
specimen, a genus not observed on this host yet. The results here presented show
that the antropic influences on natural systems alter the environmental
conditions, what is reflected on the richness and diversity parasite levels.
PMID- 25119354
TI - Ultrastructural study of Balantidium ctenopharyngodoni Chen, 1955 (Class:
Litostomatea) from China with an emphasis on its vestibulum.
AB - A detailed description of the fine structure of Balantidium ctenopharyngodoni
Chen, 1955 with an emphasis on its vestibulum is given in the present paper. As
to the vestibular kinetids, special attention is paid to the characters of T1, T2
microtubules and nematodesmata. Serving as the major skeleton to the vestibular
cortex, the T1, T2 and Pc microtubules are described herein and their support
function is also discussed. Moreover, the well-developed nematodesmata of the
vestibular kinetids that form a large basket-like complex are described in
detail.
PMID- 25119353
TI - Molecular characterization of two opecoelid trematodes from fishes in the Gulf of
Mexico, with a description of a new species of Helicometra.
AB - The plagioporine opecoelids Helicometra fasciata (Rudolphi, 1819) Odhner, 1902,
and Macvicaria crassigula (Linton, 1910) Bartoli, Bray, and Gibson, 1989 have
been reported from fishes in expansive geographic regions, disjointed from their
type localities. New material of M. crassigula was collected from near its type
locality as well as specimens resembling Helicometra fasciata sensu lato from
three triglids in the Gulf of Mexico. Comparisons of the ribosomal DNA (rDNA)
sequences, comprising the partial 18S rDNA, internal transcribed spacer region (=
ITS1, 5.8S, and ITS2), and partial 28S rDNA gene, from M. crassigula and
Helicometra fasciata sensu lato in the Gulf of Mexico were made with sequences
deposited in GenBank from those species from the Mediterranean Sea. Results
reveal that M. crassigula sensu stricto from the Gulf of Mexico is distinct from
the two cryptic species of M. crassigula sensu lato from the Mediterranean Sea
and Helicometra fasciata sensu lato in this study differs from H. fasciata
sequences from the Mediterranean Sea, thus Helicometra manteri sp. nov. is
described.
PMID- 25119356
TI - Calamicoptes anatidus sp. nov., a new quill wall mite (Acari: Laminosioptidae)
from the Greater Scaup Aythya marila (L.) (Aves: Anseriformes).
AB - Calamicoptes anatidus sp. nov., a new species of rarely found parasitic mites of
the family Laminosioptidae (Acari: Astigmata) is described from quill walls of
wing covert feathers of Aythya marila Linnaeus (Anseriformes: Anatidae) captured
in Poland. This is the first record of the family Laminosioptidae on birds of the
order Anseriformes and the first record of this mite family in the fauna of
Poland. Females of the new species are most similar to those of C. arenariae
Lombert, Gaud et Lukoschus, 1984 and differ from them by the presence of the
pygidial shield, which covers dorsal and ventro-lateral parts of the opisthosoma,
and by having setae c2 and d2 short and subequal in length, and setae se and cp
not reaching the metapodonotal shield.
PMID- 25119355
TI - Grillotia erinaceus (van Beneden, 1858) (Cestoda:Trypanorhyncha) from whiting in
the Black Sea, with observations on seasonality and host-parasite
interrelationship.
AB - The genus Grillotia Guiart, 1927 is cosmopolitan in its distribution and the type
species, G. erinaceus (van Beneden, 1858), has been relatively well studied.
However, this study provides infection indices of Grillotia erinaceus from
southern and northern Black Sea whiting Merlangius merlangus for the first time.
The specimens of Grillotia erinaceus were obtained from subserosa of the anterior
oesophagus, stomach, pyloric caeca, liver, ovaries and mesenterium of whiting
caught by commercial fishing vessels off Sinop, Turkey and off Balaklava,
Ukraine. Fish were examined during the period from May 2011 to April 2012.
Prevalence and mean intensity values in 268 fish collected off Sinop in the Black
Sea were 18.66% and 1.82 +/- 0.16 parasites per infected fish, respectively. In
Ukrainian 166 whiting samples collected off Balaklava in the Black Sea, however,
G. erinaceus plerocercus infection prevalence was 10.24% and mean intensity 1.71
+/- 0.75 parasites per infected fish. Infection parameters were also determined
at both sampling sites in relation with host length, sex and season.
PMID- 25119358
TI - Seven new species of helminths for reptiles from Armenia.
AB - Helminthic infections of reptiles habiting in the territory of Armenia are
examined. Seven species of helminths new for reptiles from Armenia are
registered: Parapharyngodon skrjabini, Oswaldocruzia goezei, Neoxysomatium sp.,
Telorchis assula, Nematotaenia tarentolae, Mesocestoides lineatus and Spirometra
erinacei europea. Descriptions and pictures of them are given.
PMID- 25119357
TI - Thermophilic potentially pathogenic amoebae isolated from natural water bodies in
Poland and their molecular characterization.
AB - The free-living amoebae (FLA) may live in the environment and also within other
organisms as parasites and then they are called amphizoic. They are potentially
pathogenic for humans and animals and are found in water that is a source of
infection. The aim of this study was molecular detection and identification of
these FLA in natural water bodies in North-Western Poland to evaluate the risk of
the pathogenic amoebae infections. We examined surface water samples collected
from 50 sites and first, the tolerance thermic test was performed in order to
select thermophilic, potentially pathogenic strains. For molecular identification
of FLA, regions of 18S rDNA, 16S rDNA and intergenic spacers were amplified.
Acanthamoeba T4 and T16 genotypes of 18S rDNA gene and 18S rDNA of H. vermiformis
were detected. We identified two variants of Acanthamoeba T4 genotype, two
variants of Acanthamoeba T16 genotype and one variant of H. vermiformis.
Identification of the T16 genotype and H. vermiformis in water was for the first
time in Poland. Additionally, we made attempts to adapt the RLB method for
detection and differentiation of FLA species and strains. PCR seems to be more
sensitive than RLB hybridization, though.
PMID- 25119359
TI - Molecular detection and characterization of Theileria species in the Philippines.
AB - Theileriosis is a tick-borne disease of domestic and wild animals that cause
devastating economic loss in livestock in tropical and subtropical regions.
Theileriosis is not yet documented in the Philippines as compared to babesiosis
and anaplasmosis which are considered major tick-borne diseases that infect
livestock in the country and contribute major losses to the livestock industry.
The study was aimed to detect Theileria sp. at genus level in blood samples of
cattle using polymerase chain reaction (PCR) assay. Specifically, it determined
the phylogenetic relationship of Theileria species affecting cattle in the
Philippines to other Theileria sp. registered in the GenBank. A total of 292
blood samples of cattle that were collected from various provinces were used.
Theileria sp. was detected in 43/292 from the cattle blood samples using PCR
assay targeting the major piroplasm surface protein (MPSP) gene. DNA sequence
showed high similarity (90-99%) among the reported Theileria sp. isolates in the
GenBank and the Philippine isolates of Theileria. Phylogenetic tree construction
using nucleotide sequence classified the Philippine isolates of Theileria as
benign. However, nucleotide polymorphism was observed in the new isolate based on
nucleotide sequence alignment. It revealed that the new isolate can be a new
species of Theileria.
PMID- 25119360
TI - Repeat region of Brugia malayi sheath protein (Shp-1) carries Dominant B epitopes
recognized in filarial endemic population.
AB - Transmission of lymphatic filariasis is mediated through microfilariae (L1 stage
of the parasite) which is encased in an eggshell called sheath. The sheath
protein Shp-1 stabilizes the structure due to the unique repeat region with Met
Pro-Pro-Gln-Gly sequences. Microfilarial proteins could be used as transmission
blocking vaccines. Since the repeat region of Shp-1 was predicted to carry
putative B epitopes, this region was used to analyze its reactivity with clinical
samples towards construction of peptide vaccine. In silico analysis of Shp-1
showed the presence of B epitopes in the region 49-107. The polypeptide epitopic
region Shp-149-107 was cloned and expressed in Escherichia coli. Antibody
reactivity of the Shp-149-107 construct was evaluated in filarial endemic
population by ELISA. Putatively immune endemic normals (EN) showed significantly
high reactivity (P < 0.05) when compared to all the other categories. Antibody
reactivity of Shp-1 repeat region was similar to that of whole protein proving
that this region carries B epitopes responsible for its humoral response in
humans. Thus this can be employed for inducing anti-microfilarial immunity in the
infected population that may lead to reduction in transmission intensity and also
it could be used along with other epitopes from different stages of the parasite
in order to manage the disease effectively.
PMID- 25119361
TI - The helminth fauna study of European common brown frog (Rana temporaria Linnaeus,
1758) in the Volga basin.
AB - In this paper we considered information on the helminth fauna of the European
common brown frog (Rana temporaria Linnaeus, 1758) from 10 regions of the Volga
basin. This study includes consolidated data of different authors over the last
30 years, supplemented by the results of our own research. There are reliably
known finds of 29 species of helminths: Monogenea - 1, Trematoda - 21, Nematoda -
7. Trematodes Gorgodera asiatica Pigulevsky, 1945, Paralepoderma cloacicola
(Luhe, 1909), mtc. and nematodes Icosiella neglecta (Diesing, 1851) were observed
for the first time in a given host on the territory of Russia and the Volga
Basin. Six species of worms make the basis of helminth fauna: nematodes Rhabdias
bufonis, Oswaldocruzia filiformis, Neoxysomatium brevicaudatum and Cosmocerca
ornata, trematode Haplometra cylindracea and monogenea Polystoma integerrimum.
These six species are the most common and widespread parasites of the brown frog.
For each species of helminths there is the following information included:
taxonomic position, localization, area of detection, biology, definitive hosts,
geographic distribution, the degree of host-specificity.
PMID- 25119362
TI - Comparative analyses of different genetic markers for the detection of
Acanthamoeba spp. isolates.
AB - Acanthamoeba are widespread free-living amoebae which may cause granulomatous
amoebic encephalitis (GAE), keratitis, skin ulcerations and disseminated tissue
infection. An important diagnostic and prognostic factor for the treatment of
infection is a quick and correct diagnosis of amoebae strains. The aim of our
study was to develop a rapid method for detection and identification of
pathogenic Acanthamoeba spp. strains from diagnostic material collected from
water. In this study we analysed five amplification-based genetic markers (Aca
16S, Ac6/210, GP, JDP, Nelson) used for identification of pathogenic Acanthamoeba
spp. strains isolated in water sources in Poland, Iceland and Sweden. Our results
demonstrated the presence of pathogenic Acanthamoeba strains in tap water. PCR
assay appeared to be a more rapid and sensitive method to detect the presence of
amoebae than the limited conventional techniques. Based on our observations, we
can confirm that the use of four out of five genetic markers (Aca 16S, Ac 6/210,
JDP, GP, Nelson) may be helpful in identification of Acanthamoeba spp. strains,
but only one Aca 16S primer pair is a highly specific marker that distinguishes
between pathogenic strains of Acanthamoeba and other free-living amoeba families.
PMID- 25119363
TI - Foleyellides rhinellae sp. nov. (Nematoda, Onchocercidae) a new filaria
parasitizing Rhinella marina (Anura, Bufonidae) in Mexico.
AB - A new nematode species, Foleyellides rhinellae sp. nov. (Onchocercidae), is
described from specimens found in the body cavity of the cane toad, Rhinella
marina (Linnaeus) (Anura, Bufonidae), in the Laguna de Coyuca, Guerrero, in the
Pacific slope of Mexico. The new species differs from the other nine species of
Foleyellides by infecting bufonid anurans and by the number and arrangement of
caudal papillae. Other distinguishing feature of the new species is the size of
the left spicule (0.16-0.23 long), the smallest recorded among the species
included in the genus. Foleyellides rhinellae sp. nov. is the second known
species of the genus recorded from amphibians of Mexico.
PMID- 25119364
TI - Monogenean parasites from fishes of the Vaal Dam, Gauteng Province, South Africa
II. New locality records.
AB - Baseline information on parasitic infections, including monogenean infections on
wild fishes, may aid in implementation of proactive measures as opposed to
reactive research aimed at crisis control with reference to future aquaculture
applications. The aim of this project was to examine the freshwater monogenean
fauna of the Vaal Dam, Vaal River system, South Africa. This short communication
reports on infection statistics for monogenean species, some representing new
locality records. Parasites were collected from host species other than Labeo
spp. from the Vaal Dam, during a summer (January 2010) survey. Fish collected
using gill nets of varying mesh sizes were weighed and measured. Mucous smears
were prepared from the skin and fins with the aid of microscope slides. Fish were
killed humanely by severing the spinal cord behind the head. Gills were carefully
removed and divided into areas which were separately scraped to investigate
potential parasite site preference. The areas examined were dorsal, median and
ventral positions on both the anterior and posterior hemibranch. Both mucous
smears and gill scrapings were examined with the aid of a stereo microscope. More
parasites were collected from the first or second gill arches, the medial
position on the gill, and the anterior hemibranch. Preference for either left or
right gill set was inconclusive. Spatial distribution of parasites is thought to
result from water flow over the gills during respiration. This paper reports a
new locality record for the following monogenean species: Quadriacanthus
aegypticus, Dactylogyrus extensus, Dactylogyrus minitus, Gyrodactylus kherulensis
and Dactylogyrus lamellatus.
PMID- 25119365
TI - Ocular system involvement in the course of human trichinellosis. Pathological and
diagnostic aspects.
AB - Pathomechanism of lesions in the course of trichinellosis was discussed,
representing a sum of immunopathologicaI, pathomorphological and biochemical
phenomena. Particular attention was devoted to clinical pathology of the visual
organ, which prevails at the acute stage of trichinellosis. In evaluation of
clinical signs/symptoms manifested in the visual organ traits of its anatomic,
morphological structure, function of the eyeball muscles and eyeball vascular
system were taken into account. Ocular lesions in the course of trichinellosis
reflect in principle angiomyositis due to immunopathology resulting from
migration of Trichinella larvae to many organs and to structures of visual
system.
PMID- 25119366
TI - Differences in snail ecology lead to infection pattern variation of Echinostoma
spp. larval stages.
AB - The infection patterns of parasites are often tied to host behavior. Although
most studies have investigated definitive hosts and their parasites, intermediate
host behavior may play a role in shaping the distribution and accumulation of
parasites, particularly the larval stages. In an attempt to answer this question,
more than 4,500 pulmonate snails were collected from 11 states in the mid
Atlantic and Midwestern United States in the summer of 2012. These snails were
necropsied and echinostome metecercariae were commonly observed infecting the
snails as 2(nd) intermediate hosts (20.0%). The snails included species of 3
genera with distinct differences in the infection patterns of Echinostoma spp.
metacercariae among them. Physa spp. (comprising of P. acuta and P. gyrina)
snails exhibited a significantly higher prevalence of infection (23.5%) than both
Lymnaea columella (11.6%) and Helisoma spp. (comprising of H. anceps and H.
trivolvis) (14.2%; P < 0.05), with no difference in prevalence observed between
the latter 2 genera (P > 0.05). The intensity of metacercariae within the snail
hosts was significantly different between the 3 genera (P < 0.05), with L.
columella having the highest intensity (24.3 +/- 5.6), followed by Physa spp.
(15.2 +/- 1.5) and Helisoma spp. (5.0 +/- 0.9). Differences in prevalence and
intensity were also observed when the different snail families co-habited the
same body of water. The disparities in infection patterns are likely due to
distinct differences in the behavioral and feeding ecology of the snail hosts.
PMID- 25119367
TI - A new brachycladiid species (Digenea) from Gervais' beaked whale Mesoplodon
europaeus in north-western Atlantic waters.
AB - A new species of the digenean family Brachycladiidae Odhner, 1905 is described
from the bile ducts of a Gervais' beaked whale Mesoplodon europaeus Gervais
(Ziphiidae) stranded on the North Atlantic coast of Florida. These parasites were
assigned to Brachycladium Looss, 1899 and differed from other species of the
genus in the relative size of the oral and ventral suckers, the form and size of
the eggs and their extremely small body size. A canonical discriminant analysis
was used to examine differences between these specimens and the smallest
available individuals of B. atlanticum (Abril, Balbuena and Raga, 1991) Gibson,
2005, considered the morphologically closest species. The overall results
exhibited significant differences between the two samples and a jack-knife
classification showed that 96.2% of the specimens were correctly classified to
their group. In view of evidence from morphological data, the specimens from M.
europaeus are considered as new to science and are designated as Brachycladium
parvulum n. sp.
PMID- 25119368
TI - Metazoan parasites from herring (Clupea harengus L.) as biological indicators in
the Baltic Sea.
AB - Zoographical distribution of metazoan fish parasites in herring, Clupea harengus,
from the Baltic Sea was analysed in order to use them as potential biological
indicators. A total of 210 herring from six different sampling sites were
investigated, harbouring 12 different parasite species [five digeneans (D), one
cestode (C), three nematodes (N) and three acanthocephalans (A)]. The
distribution of the parasite species differed according to region, with a
distinct gradient of decreasing species richness towards the east of the Baltic
Sea. The western localities at Kiel Bay, Rugen and Poland had the highest
parasite diversity, including the marine parasite species Anisakis simplex (s.s.)
(N), Brachyphallus crenatus and Hemiurus luehei (both D). The eastern localities
had low parasite species richness, predominated by the freshwater digenean
Diplostomum spathaceum. We could identify three different Baltic herring stocks,
the spring-spawning herring of the western Baltic reaching from the Kattegat to
the German and Polish coast, the stock of the central Baltic proper and the
northern stock of C. harengus var. membras of the Gulf of Finland. The limited
distribution of the herring parasites within the Baltic Sea enables their use as
biological indicators for migration patterns and stock separation. The
acanthocephalan Pomphorhynchus laevis that has already been used as an
accumulation bioindicator for heavy metals was only recorded for the western
herring stocks. However, the presence of mainly generalistic parasites and their
uneven distribution patterns make their use as indicators for regional
environmental and global change more difficult.
PMID- 25119369
TI - Identifying phenotypes involved in susceptibility to Schistosoma mansoni
infection in F1B6CBA mice.
AB - Schistosomiasis is a disease with a strong genetic component influenced by
socioeconomic and ecological factors. Epidemiological studies have identified
several genetic regions involved in the schistosomiasis susceptibility. However,
it is not well known what physiological traits are predisposing to the disease.
The study of experimental infections in inbred mouse strains with variable
genetic susceptibility to the disease offers a good opportunity to tackle this
question. F1B6CBA hybrid between the most divergent strains was infected in order
to characterize the immunophenotypes that correlate with the susceptibility of
schistosomiasis disease in mice. Complete blood counts and immunophenotype were
determined at 0, 3, 6, and 9 weeks post infection. Nine weeks after cercariae
exposure, animals were perfused and worm recovery was assessed. A large number of
hepatic lesions, a reduction in the eosinophil and basophil count in the acute
phase of infection and the decreased number of monocytes, neutrophils and B
lymphocytes are phenotypes associated with increased susceptibility to S. mansoni
infection.
PMID- 25119370
TI - A new species of Rhinonastes (Monogenoidea, Dactylogyridae), nasal parasite of
Prochilodus argenteus (Actinopterygii, Characiformes) from Brazil.
AB - A new species of Rhinonastes, hitherto monotypic, is described and illustrated
from the nasal cavity of 'curimat', Prochilodus argenteus from Sao Francisco
River, Brazil. Rhinonastes curimatae n. sp. presents a male copulatory organ with
more than five rings while the type species of the genus is characterized by male
copulatory organ with less than two rings. This is the first record of a nasal
parasite in P. argenteus.
PMID- 25119371
TI - Observations on oocyst development of Eimeria stiedai in rabbits.
AB - The formation of the oocyst wall was examined in Eimeria stiedai in the bile duct
epithelium of the rabbit and was found to follow the general eimerian pattern.
However from the beginning of the formation of the outer layer of the oocyst wall
the parasite was surrounded by a rarely reported veil membrane. Cell damage of
the bile ducts at the gamogony stage of parasite development is depicted.
PMID- 25119372
TI - Increased serum urea to creatinine ratio and its negative correlation with
arterial pressure in canine babesiosis.
AB - The increase of the serum urea to creatinine ratio (UCR) was observed in dogs
infected with Babesia canis. Previous studies have suggested that decrease of
blood pressure can be one of the reasons for this phenomenon. In this work
statistically significant increase of the UCR was observed in dogs with
babesiosis. Comparison of the UCR between 23 azotaemic dogs and 25 non-azotaemic
dogs infected with Babesia canis showed statistically significantly higher mean
of the UCR in azotaemic dogs. Correlations between UCR and systolic, diastolic
and mean arterial pressure (SAP, DAP and MAP) in 48 dogs infected with B. canis
were negative (UCR and SAP: r = -0.3909; UCR and DAP: r = -0.3182; UCR and MAP: r
= -0.3682) and statistically significant (p < 0.05). This result may indicate
contribution of hypotension in the increase of the UCR in canine babesiosis.
However, the correlations were not high, and there was no statistically
significant correlation between UCR and arterial pressures in azotaemic dogs.
Thus, it seems that decrease of blood pressure in dogs with babesiosis explains
only partially the cause of increased UCR in infected dogs. The other authors
suggested hyperureagenesis and myocardial injury as a potential reason for the
increased UCR in canine babesiosis. Thus, further studies are needed to determine
causes of increased UCR in dogs with babesiosis, especially on the connection
between UCR changes and the concentrations of plasma cardiac troponins and
ammonia, and the occurrence of occult blood on fecal examination.
PMID- 25119373
TI - Individual growth detection of bacterial species in an in vitro oral
polymicrobial biofilm model.
AB - Most in vitro studies on the antibacterial effects of antiseptics have used
planktonic bacteria in monocultures. However, this study design does not reflect
the in vivo situation in oral cavities harboring different bacterial species that
live in symbiotic relationships in biofilms. The aim of this study was to
establish a simple in vitro polymicrobial model consisting of only three
bacterial strains of different phases of oral biofilm formation to simulate in
vivo oral conditions. Therefore, we studied the biofilm formation of Actinomyces
naeslundii (An), Fusobacterium nucleatum (Fn), and Enterococcus faecalis (Ef) on
96-well tissue culture plates under static anaerobic conditions using artificial
saliva according to the method established by Pratten et al. that was
supplemented with 1 g l(-1) sucrose. Growth was separately determined for each
bacterial strain after incubation periods of up to 72 h by means of quantitative
real-time polymerase chain reaction and live/dead staining. Presence of an
extracellular polymeric substance (EPS) was visualized by Concanavalin A
staining. Increasing incubation times of up to 72 h showed adhesion and
propagation of the bacterial strains with artificial saliva formulation. An and
Ef had significantly higher growth rates than Fn. Live/dead staining showed a
median of 49.9 % (range 46.0-53.0 %) of living bacteria after 72 h of incubation,
and 3D fluorescence microscopy showed a three-dimensional structure containing
EPS. An in vitro oral polymicrobial biofilm model was established to better
simulate oral conditions and had the advantage of providing the well-controlled
experimental conditions of in vitro testing.
PMID- 25119374
TI - Interactive sections of an Internet-based intervention increase empowerment of
chronic back pain patients: randomized controlled trial.
AB - BACKGROUND: Chronic back pain (CBP) represents a significant public health
problem. As one of the most common causes of disability and sick leave, there is
a need to develop cost-effective ways, such as Internet-based interventions, to
help empower patients to manage their disease. Research has provided evidence for
the effectiveness of Internet-based interventions in many fields, but it has paid
little attention to the reasons why they are effective. OBJECTIVE: This study
aims to assess the impact of interactive sections of an Internet-based self
management intervention on patient empowerment, their management of the disease,
and, ultimately, health outcomes. METHODS: A total of 51 patients were recruited
through their health care providers and randomly assigned to either an
experimental group with full access to the Internet-based intervention or a
control group that was denied access to the interactive sections and knew nothing
thereof. The intervention took 8 weeks. A baseline, a mid-term after 4 weeks, and
a final assessment after 8 weeks measured patient empowerment, physical exercise,
medication misuse, and pain burden. RESULTS: All patients completed the study.
Overall, the intervention had a moderate effect (F1.52=2.83, P=.03, eta(2)=0.30,
d=0.55). Compared to the control group, the availability of interactive sections
significantly increased patient empowerment (midterm assessment: mean
difference=+1.2, P=.03, d=0.63; final assessment: mean difference=+0.8, P=.09,
d=0.44) and reduced medication misuse (midterm assessment: mean difference=-1.5,
P=.04, d=0.28; final assessment: mean difference=-1.6, P=.03, d=-0.55) in the
intervention group. Both the frequency of physical exercise and pain burden
decreased, but to equal measures in both groups. CONCLUSIONS: Results suggest
that interactive sections as part of Internet-based interventions can positively
alter patients' feelings of empowerment and help prevent medication misuse.
Detrimental effects were not observed. TRIAL REGISTRATION: ClinicalTrials.gov:
NCT02114788; http://www.clinicaltrials.gov/ct2/show/NCT02114788 (Archived by
WebCite at http://www.webcitation.org/6ROXYVoPR).
PMID- 25119376
TI - Adeno-associated virus-mediated gene transfer targeting normal and traumatized
mouse utricle.
AB - Balance dysfunction is closely associated with loss of vestibular hair cells
(HCs). Gene therapy shows promise when used to protect or regenerate vestibular
HCs to preserve or restore adequate vestibular function. Adeno-associated virus
(AAV) vectors allow long-term gene expression in the absence of toxicity. To
noninvasively define an AAV serotype exhibiting favorable tropism toward the
vestibular sensory epithelium, we characterized the transgene expression
potential of AAV vectors (serotypes 1, 2, 5, 6 and 8) inoculated into adult mouse
utricle via canalostomy. We found that AAV8 was the most effective AAV vector in
utricular gene transfer. Swim tests and measurements of auditory brainstem
response revealed minimal loss of vestibular function and hearing after
canalostomy. In the normal utricle after AAV8 infusion, transduction efficiency
peaked at 7 days, and was maintained thereafter, in vestibular HCs, and at 3 days
in supporting cells (SCs). In the streptomycin-lesioned utricle, the SC
transduction efficiency peaked at 7 days and decreased at 30 days. In conclusion,
AAV8-mediated gene transfer via canalostomy facilitates efficient and safe
transduction in mouse vestibular sensory epithelium, and may in the future become
clinically relevant for human vestibular gene therapy.
PMID- 25119375
TI - Adjuvant effects of L. acidophilus LW1 on immune responses to the foot-and-mouth
disease virus DNA vaccine in mice.
AB - The adjuvant effects of Lactobacillus acidophilus on DNA vaccination are not
fully understood. It has been hypothesized that swine-derived Lactobacillus
acidophilus SW1 (LASW1) could function as an immune adjuvant to enhance antigen
specific immune responses after foot-and-mouth disease (FMD) DNA vaccination in
mice. To evaluate the effect of oral LASW1 on the immune response to a DNA
vaccine (pRC/CMV-vp1) harboring FMD VP1 gene, anti-FMDV antibody and its
isotypes, T-cell proliferation, and cytokine detection were investigated. The
results showed that LASW1 was able to enhance FMDV-specific antibody levels and
FMDV-neutralizing antibodies. After a booster vaccine, the anti-FMDV antibody
titers and FMDV-neutralizing antibodies levels induced by pRC/CMV-vp1 were higher
in mice treated with LSAW1 than in the group immunized with pRC/CMV-vp1 alone
(the control). Using T-cell proliferation, the stimulation index of the LASW1
group was significantly higher in response to ConA and 146S antigen (P<0.05) than
in the control group. Importantly, higher concentrations of IFN-gamma and IFN
gamma-producing cells were also observed in splenocytes isolated from the
experimental LASW1 mice, indicating that INF-gamma secretion is important to the
immune response to LASW1. The results indicate that LASW1 is a promising immune
adjuvant in DNA vaccination against FMD when administrated orally.
PMID- 25119378
TI - Transduction efficiency of neurons and glial cells by AAV-1, -5, -9, -rh10 and
hu11 serotypes in rat spinal cord following contusion injury.
AB - Adeno-associated viruses (AAVs) are a promising system for therapeutic gene
delivery to neurons in a number of neurodegenerative conditions including spinal
cord injuries (SCIs). Considering the role of macrophages and glia in the
progression of 'secondary damage', we searched for the optimal vectors for gene
transfer to both neurons and glia following contusion SCI in adult rats.
Contusion models share many similarities to most human spinal cord traumas.
Several AAV serotypes known for their neuronal tropism expressing enhanced green
fluorescent protein (GFP) were injected intraspinally following thoracic T10
contusion. We systematically compared the transduction efficacy and cellular
tropism of these vectors for neurons, macrophages/microglia, oligodendrocytes,
astrocytes and NG2-positive glial cells following contusion SCI. No additional
changes in inflammatory responses or behavioral performance were observed for any
of the vectors. We identified that AAV-rh10 induced robust transduction of both
neuronal and glial cells. Even though efficacy to transduce neurons was
comparable to already established AAV-1, AAV-5 and AAV-9, AAV-rh10 transduced
significantly higher number of macrophages/microglia and oligodendrocytes in
damaged spinal cord compared with other serotypes tested. Thus, AAV-rh10 carries
promising potential as a gene therapy vector, particularly if both the neuronal
and glial cell populations in damaged spinal cord are targeted.
PMID- 25119380
TI - Whole-genome mapping for high-resolution genotyping of Pseudomonas aeruginosa.
AB - A variety of molecular typing techniques have been developed to investigate the
clonal relationship among bacterial isolates, including those associated with
nosocomial infections. In this study, the authors evaluated whole-genome mapping
as a tool to investigate the genetic relatedness between Pseudomonas aeruginosa
isolates, including metallo beta-lactamase-positive outbreak isolates.
PMID- 25119377
TI - SR-A and SREC-I binding peptides increase HDAd-mediated liver transduction.
AB - Helper-dependent adenoviral (HDAd) vectors can mediate long-term, high-level
transgene expression from transduced hepatocytes without inducing chronic
toxicity. However, vector therapeutic index is narrow because of a toxic acute
response with potentially lethal consequences elicited by high vector doses.
Kupffer cells (KCs) and liver sinusoidal endothelial cells (LSECs) are major
barriers to efficient hepatocyte transduction. We investigated two small peptides
(PP1 and PP2) developed by phage display to block scavenger receptor type A (SR
A) and scavenger receptor expressed on endothelial cells type I (SREC-I),
respectively, for enhancement of HDAd-mediated hepatocyte transduction
efficiency. Pre-incubation of J774A.1 macrophages with either PP1 or PP2 prior to
HDAd infection significantly reduced viral vector uptake. In vivo, fluorochrome
conjugated PP1 and PP2 injected intravenously into mice co-localized with both
CD68 and CD31 on KCs and LSECs, respectively. Compared with saline pre-treated
animals, intravenous injections of both peptides prior to the injection of an
HDAd resulted in up to 3.7- and 2.9-fold increase of hepatic transgene expression
with PP1 and PP2, respectively. In addition to greater hepatocyte transduction,
compared with control saline injected mice, pre-treatment with either peptide
resulted in no increased levels of serum interleukin-6, the major marker of
adenoviral vector acute toxicity. In summary, we developed small peptides that
significantly increase hepatocyte transduction efficacy and improve HDAd
therapeutic index with potential for clinical applications.
PMID- 25119381
TI - Soil carbon and nitrogen fractions and crop yields affected by residue placement
and crop types.
AB - Soil labile C and N fractions can change rapidly in response to management
practices compared to non-labile fractions. High variability in soil properties
in the field, however, results in nonresponse to management practices on these
parameters. We evaluated the effects of residue placement (surface application
[or simulated no-tillage] and incorporation into the soil [or simulated
conventional tillage]) and crop types (spring wheat [Triticum aestivum L.], pea
[Pisum sativum L.], and fallow) on crop yields and soil C and N fractions at the
0-20 cm depth within a crop growing season in the greenhouse and the field. Soil
C and N fractions were soil organic C (SOC), total N (STN), particulate organic C
and N (POC and PON), microbial biomass C and N (MBC and MBN), potential C and N
mineralization (PCM and PNM), NH4-N, and NO3-N concentrations. Yields of both
wheat and pea varied with residue placement in the greenhouse as well as in the
field. In the greenhouse, SOC, PCM, STN, MBN, and NH4-N concentrations were
greater in surface placement than incorporation of residue and greater under
wheat than pea or fallow. In the field, MBN and NH4-N concentrations were greater
in no-tillage than conventional tillage, but the trend reversed for NO3-N. The
PNM was greater under pea or fallow than wheat in the greenhouse and the field.
Average SOC, POC, MBC, PON, PNM, MBN, and NO3-N concentrations across treatments
were higher, but STN, PCM and NH4-N concentrations were lower in the greenhouse
than the field. The coefficient of variation for soil parameters ranged from 2.6
to 15.9% in the greenhouse and 8.0 to 36.7% in the field. Although crop yields
varied, most soil C and N fractions were greater in surface placement than
incorporation of residue and greater under wheat than pea or fallow in the
greenhouse than the field within a crop growing season. Short-term management
effect on soil C and N fractions were readily obtained with reduced variability
under controlled soil and environmental conditions in the greenhouse compared to
the field. Changes occurred more in soil labile than non-labile C and N fractions
in the greenhouse than the field.
PMID- 25119379
TI - Assessment of oncolytic HSV efficacy following increased entry-receptor
expression in malignant peripheral nerve sheath tumor cell lines.
AB - Limited expression and distribution of nectin-1, the major herpes simplex virus
(HSV) type-1 entry-receptor, within tumors has been proposed as an impediment to
oncolytic HSV (oHSV) therapy. To determine whether resistance to oHSVs in
malignant peripheral nerve sheath tumors (MPNSTs) was explained by this
hypothesis, nectin-1 expression and oHSV viral yields were assessed in a panel of
MPNST cell lines using gamma134.5-attenuated (Deltagamma134.5) oHSVs and a
gamma134.5 wild-type (wt) virus for comparison. Although there was a correlation
between nectin-1 levels and viral yields with the wt virus (R=0.75, P =0.03),
there was no correlation for Deltagamma134.5 viruses (G207, R7020 or C101) and a
modest trend for the second-generation oHSV C134 (R=0.62, P=0.10). Nectin-1
overexpression in resistant MPNST cell lines did not improve Deltagamma134.5 oHSV
output. While multistep replication assays showed that nectin-1 overexpression
improved Deltagamma134.5 oHSV cell-to-cell spread, it did not confer a sensitive
phenotype to resistant cells. Finally, oHSV yields were not improved with
increased nectin-1 in vivo. We conclude that nectin-1 expression is not the
primary obstacle of productive infection for Deltagamma134.5 oHSVs in MPNST cell
lines. In contrast, viruses that are competent in their ability to counter the
antiviral response may derive benefit with higher nectin-1 expression.
PMID- 25119383
TI - Factors associated with recently acquired hepatitis C virus infection in people
who inject drugs in England, Wales and Northern Ireland: new findings from an
unlinked anonymous monitoring survey.
AB - Monitoring infections and risk in people who inject drugs (PWID) is important for
informing public health responses. In 2011, a novel hepatitis C antibody (anti
HCV) avidity-testing algorithm to identify samples compatible with recent primary
infection was introduced into a national surveillance survey. PWID are recruited
annually, through >60 needle-and-syringe programmes and prescribing services. Of
the 980 individuals that could have been at risk of HCV infection, there were 20
(2%) samples that were compatible with recent primary infection. These were more
common among: those imprisoned ?5 times [8/213; adjusted odds ratio (aOR) 8.7,
95% confidence interval (CI) 2.04-37.03]; women (8/230; aOR 3.8, 95% CI 1.41
10.38); and those ever-infected with hepatitis B (5/56; aOR 6.25, 95% CI 2.12
18.43). This study is the first to apply this algorithm and to examine the risk
factors associated with recently acquired HCV infection in a national sample of
PWID in the UK. These findings highlight underlying risks and suggest targeted
interventions are needed.
PMID- 25119382
TI - Innate immunodeficiency following genetic ablation of Mcl1 in natural killer
cells.
AB - The cytokine IL-15 is required for natural killer (NK) cell homeostasis; however,
the intrinsic mechanism governing this requirement remains unexplored. Here we
identify the absolute requirement for myeloid cell leukaemia sequence-1 (Mcl1) in
the sustained survival of NK cells in vivo. Mcl1 is highly expressed in NK cells
and regulated by IL-15 in a dose-dependent manner via STAT5 phosphorylation and
subsequent binding to the 3'-UTR of Mcl1. Specific deletion of Mcl1 in NK cells
results in the absolute loss of NK cells from all tissues owing to a failure to
antagonize pro-apoptotic proteins in the outer mitochondrial membrane. This NK
lymphopenia results in mice succumbing to multiorgan melanoma metastases, being
permissive to allogeneic transplantation and being resistant to toxic shock
following polymicrobial sepsis challenge. These results clearly demonstrate a non
redundant pathway linking IL-15 to Mcl1 in the maintenance of NK cells and innate
immune responses in vivo.
PMID- 25119385
TI - Adjuvant chemoradiotherapy for squamous cell carcinoma of gallbladder.
PMID- 25119386
TI - Mesenteric inflammatory pseudotumor: a case report and comprehensive literature
review.
AB - PURPOSE: This study aims to provide an overview of the literature on
mesenteric/omental inflammatory pseudotumors (IPTs). METHODOLOGY: We present a
new case of mesenteric IPT. We also conducted a systematic search of the English
language medical literature using PubMed, Medline, Google, and Google Scholar
related to mesenteric or omental IPTs. The following search terms were used in
various combinations: inflammatory myofibroblastic tumor, IPT, mesentery, and
omentum. The search included articles published in the English language between
January, 1978 and April, 2014. Studies were excluded if the full text was
unavailable or missing information prohibited comparisons. RESULTS: A total of 30
reports concerning 36 patients with inflammatory pseudotumors meeting the
aforementioned criteria were included. The patients were aged from 10 months to
68 years (mean, 19.98 +/- 20.5 years); 12 were female (16.75 +/- 16.97 years;
range, 10 months to 68 years) and 24 were male (21.6 +/- 21.9 years; range, 18
months to 63 years). Detailed clinical and pathologic characteristics of 36
patients with IPTs are provided in Table 1. CONCLUSION: IPTs may be definitively
diagnosed only by histopathological examination and are most effectively treated
by resection with negative surgical borders. No consensus has yet been reached
regarding when nonsurgical treatment options are most appropriate in management
of these lesions. IPTs often recur locally, while distant metastases are very
rare. Postoperative close surveillance is essential to detect recurrences early.
PMID- 25119388
TI - Social-emotional aspects of male escorting: experiences of men working for an
agency.
AB - Social situations and emotional correlates associated with male sex work have not
been well documented. Most of the research in this area focuses on sexual
activity with little mention of other aspects of the job. Yet, research with
female sex workers finds significant social and emotional components to sex work.
The current study focused on how male sex workers (MSWs) perceived and adapted to
the social-emotional aspects of their job. As part of a larger project examining
MSWs working for a single escort agency, 40 men (M age, 22.3 years, 75 %
Caucasian) located in the mid-Atlantic U.S. participated in semi-structured
interviews. The agency owner was also interviewed. Participants reported a range
of social and emotional factors regarding sex work and employed a variety of
strategies to provide good customer service and adapt to negative experiences.
For most, social support was inhibited due to fear of stigmatization that might
result if participants disclosed sex work to significant others outside the
agency. Instead, interactions within the agency provided core work-related social
support for most MSWs. Emotional and relational tasks inherent to escort work
grew easier with experience and negativity about the job declined. Our data
suggested that socially connected individuals seemed to be more satisfied with
sex work. Social and emotional requirements represented a significant but
unanticipated component of male sex work to which escorts actively adapted.
Escorting may be similar to other service occupations in terms of the social
emotional situations and skills involved.
PMID- 25119387
TI - Discrimination and depressive symptoms among sexual minority youth: is gay
affirming religious affiliation a protective factor?
AB - Researchers have examined perceived discrimination as a risk factor for
depression among sexual minorities; however, the role of religion as a protective
factor is under-investigated, especially among sexual minority youth. Drawing on
a cross-sectional study investigating campus climate at a large public university
in the U.S. midwest, we examined the role of affiliation with a gay-affirming
denomination (i.e., endorsing same-sex marriage) as a moderating factor in the
discrimination-depression relationship among self-identified sexual minority (n =
393) and heterosexual youth (n = 1,727). Using multivariate linear regression
analysis, religious affiliation was found to moderate the discrimination
depression relationship among sexual minorities. Specifically, the results
indicated that the harmful effects of discrimination among sexual minority youth
affiliated with denominations that endorsed same-sex marriage were significantly
less than those among peers who affiliated with denominations opposing same-sex
marriage or who identified as secular. In contrast, religious affiliation with
gay-affirming denominations did not moderate the discrimination-depression
relationship among heterosexual participants. The findings suggest that, although
religion and same-sex sexuality are often seen as incompatible topics, it is
important when working with sexual minority clients for clinicians to assess
religious affiliation, as it could be either a risk or a protective factor,
depending on the religious group's stance toward same-sex sexuality. To promote
the well-being of sexual minority youth affiliated with denominations opposed to
same-sex marriage, the results suggest these faith communities may be encouraged
to reconsider their position and/or identify ways to foster youth's resilience to
interpersonal discrimination.
PMID- 25119389
TI - Capturing sexual violence experiences among battered women using the revised
sexual experiences survey and the revised conflict tactics scales.
AB - The assessment of intimate partner sexual violence (IPSV) has garnered increased
attention in recent years. However, uncertainty about which measure best captures
experiences of IPSV remains. The present study focused on the direct comparison
of two widely used measures of IPSV: the revised Sexual Experiences Survey (SES)
and the revised Conflict Tactics Scales (CTS2). A secondary aim of the study was
to extend the scope of IPSV acts by evaluating the presence of pornographic acts
and experiences of forced sexual relations with other individuals. The current
sample consisted of 138 battered women using the services of shelters. Results
indicated that 79.7 % of women reported at least one incident of IPSV on either
the CTS2 or the SES. The concordance rate between both measures was 76.8 %, with
the highest concordance being for severe sexual violence. The Sexual Violence
scale of the CTS2, which is more concise than the SES, identified 16.7 % more
cases of IPSV. In addition, 26.1 % of women reported at least one incident
involving pornography and 9.4 % had been forced to engage in sexual activities
with other individuals. Women who reported experiences associated with
pornography were 12-20 times more likely to be victims of severe sexual violence
on the two measures. Such findings confirm the high prevalence of sexual violence
among this population and indicate how rates can vary depending on the measures
used. This study also underscores the relevance of investigating diverse types of
violent acts to better understand how IPSV manifests itself.
PMID- 25119390
TI - Hepatitis B virus inhibits the expression of CD82 through hypermethylation of its
promoter in hepatoma cells.
AB - The tumor suppressor gene CD82, also known as KAI1, may act as a general
suppressor of metastasis in numerous types of cancer. It is hypothesized that
downregulation of CD82 gene expression may be an important factor in the
induction of hepatocellular carcinoma (HCC), however the mechanism for this
requires further study. In the present study, the relative mRNA and protein
expression levels of the CD82 gene were determined in HCC and adjacent non-tumor
tissues. The association between the CD82 gene and the hepatitis B virus (HBV)
was also investigated, by quantitative polymerase chain reaction, western
blotting, luciferase reporter assays and mass spectrometry with matrix-assisted
laser desorption/ionization time-of-flight mass array. CD82 expression was shown
to be suppressed in response to HCC promoter methylation. Relative CD82 mRNA and
protein expression levels were downregulated in HCC tissues (P<0.05). HBx protein
inhibited CD82 promoter activity and subsequently the mRNA and protein expression
levels. Furthermore, it was demonstrated that HBV could inhibit the expression of
CD82 at the transcriptional level, and repress the activity of the CD82 promoter
through hypermethylation. In addition, the methyl enzyme inhibitor 5-aza-CdR
could induce the CD82 promoter activity and the relative expression level of CD82
mRNA, as observed by an increase in luciferase activity driven by the CD82
promoter. The observations of the present study suggest that hypermethylation of
the CD82 promoter may be an event leading to the development of HCC. Low
expression of CD82 is likely to be involved in tumor progression. HBV may inhibit
the expression of CD82 through hypermethylation of the promoter in hepatoma
cells.
PMID- 25119394
TI - Oral bacillus Calmette-Guerin vaccine against tuberculosis: why not?
AB - The bacillus Calmette-Guerin (BCG) vaccine is the only licensed vaccine for human
use against tuberculosis (TB). Although controversy exists about its efficacy,
the BCG vaccine is able to protect newborns and children against disseminated
forms of TB, but fails to protect adults against active forms of TB. In the last
few years, interest in the mucosal delivery route for the vaccine has been
increasing owing to its increased capacity to induce protective immune responses
both in the mucosal and the systemic immune compartments. Here, we show the
importance of this route of vaccination in newly developed vaccines, especially
for vaccines against TB.
PMID- 25119395
TI - The first report of the vanC1 gene in Enterococcus faecium isolated from a human
clinical specimen.
AB - The vanC1 gene, which is chromosomally located, confers resistance to vancomycin
and serves as a species marker for Enterococcus gallinarum. Enterococcus faecium
TJ4031 was isolated from a blood culture and harbours the vanC1gene. Polymerase
chain reaction (PCR) assays were performed to detect vanXYc and vanTc genes. Only
the vanXYc gene was found in the E. faecium TJ4031 isolate. The minimum
inhibitory concentrations of vancomycin and teicoplanin were 2 ug/mL and 1 ug/mL,
respectively. Real-time reverse transcription-PCR results revealed that the
vanC1and vanXYc genes were not expressed. Pulsed-field gel electrophoresis and
southern hybridisation results showed that the vanC1 gene was encoded in the
chromosome. E. faecalis isolated from animals has been reported to harbour
vanC1gene. However, this study is the first to report the presence of the
vanC1gene in E. faecium of human origin. Additionally, our research showed the
vanC1gene cannot serve as a species-specific gene of E. gallinarum and that it is
able to be transferred between bacteria. Although the resistance marker is not
expressed in the strain, our results showed that E. faecium could acquire the
vanC1gene from different species.
PMID- 25119397
TI - Ectopic tooth superiorly located in the maxillary sinus.
PMID- 25119398
TI - Malformation, deformity, and discrepancy: focus on terminology.
PMID- 25119396
TI - Odontogenic differentiation of vascular endothelial growth factor-transfected
human dental pulp stem cells in vitro.
AB - Dental pulp stem cells (DPSCs) can be induced towards odontogenic
differentiation. Previous studies have shown that vascular endothelial growth
factor (VEGF) is able to induce the osteogenic differentiation of cells, but the
effectiveness of VEGF in the odontogenic differentiation of DPSCs remains
unclear. This study aimed to investigate the effects of lentivirus-mediated human
VEGF gene transfection on the proliferation and odontogenic differentiation of
human DPSCs in vitro. DPSCs were transfected with either lentiviral pCDH-CMV-MCS
EFI-copGFP (pCDH) vector or recombinant pCDH-VEGF vector, and the growth
characteristics of the resulting DPSCs/Vector and DPSCs/VEGF were subsequently
assessed. The odontogenic differentiation genes of the two groups of cells,
including alkaline phosphatase, osteocalcin, dentin sialophosphoprotein and
dentin matrix protein 1 (DMP1), were evaluated by quantitative polymerase chain
reaction (qPCR). The specific proteins of odontogenic differentiation, including
dentin sialoprotein and DMP1, were analyzed by western blotting. DPSCs/VEGF
showed similar proliferation characteristics to DPSCs/Vector during the
observation period. qPCR results showed that the relative VEGF gene expression
was significantly higher in DPSCs/VEGF than that in DPSCs/Vector two days after
transfection (P<0.01). Similarly, western blot analysis showed that the protein
expression levels of VEGF were higher in DPSCs/VEGF than those in DPSCs/Vector.
On the first, fourth, eighth and 16th days after lentivirus-mediated
transfection, the expression of odontogenic differentiation-specific genes and
proteins was higher in DPSCs/VEGF than that in DPSCs/Vector. These results
indicated that lentivirus-mediated VEGF gene transfection promoted the
odontogenic differentiation of human DPSCs in vitro.
PMID- 25119399
TI - Pediatric Castleman disease of the parotid.
PMID- 25119401
TI - Herpes simpex infection after septorhinoplasty.
PMID- 25119400
TI - Foot ischemia after a free fibula flap harvest: immediate salvage with an
interpositional sapheneous vein graft.
AB - The most dreaded major donor-site complication of free fibula flap is a foot
ischemia, which is fortunately rare. Various authors have discussed the efficacy
of the use of preoperative imaging methods including color Doppler, magnetic
resonance angiography, and conventional angiography. A 25-year-old man presented
with a 10-cm mandibular defect after a facial gunshot injury. Lower extremity
color Doppler revealed triphasic peroneal, tibialis anterior, and posterior
artery flows. A fibula osteocutaneous flap was harvested, and the mandible was
reconstructed. However, the suture sites at the donor site began to demonstrate
signs of necrosis, abscess formation, and widespread cellulitis beginning from
postoperative day 9. Angiogram of the lower extremity on the 13th day
demonstrated no flow in the right posterior tibial artery distal to the popliteal
artery, whereas the anterior tibial artery had weak flow with collateral filling
distally. An emergency bypass with a saphenous vein graft between the popliteal
artery and the distal posterior tibial artery was performed. Repeated
debridements, local wound care, and vacuum-assisted closure were applied. A skin
graft was placed eventually. The extremity healed without severe functional
disability. In conclusion, although the arterial anatomy is completely normal in
preoperative evaluation, vascular complications may still ocur at the donor
fibula free flap site. In addition, emergency cardiovascular bypass surgery, as
we experienced, may be necessary for limb perfusion.
PMID- 25119402
TI - Papillary cystadenoma of the upper lip.
PMID- 25119403
TI - Infantile hemangioma: treatment rate during the proliferating phase.
PMID- 25119404
TI - A patient with intraoral fire during tonsillectomy.
AB - Perioperative fires inside the mouth can have long-lasting sequelae. They are
potentially dangerous both to the patient and to the operation room staff as
well. Herein, we present a flash fire in the oropharynx, secondary to
electrosurgery during a tonsillectomy operation in a young child. Despite a
potentially devastating situation, the patient recovered well within just a week
following intraoral burn injuries, and the initially interrupted tonsillectomy
operation was completed without complications. The dangerous situations leading
to fire hazards and the prevention measures are discussed.
PMID- 25119405
TI - Somatotopic organization of trigeminal ganglion: three-dimensional reconstruction
of three divisions.
AB - Clearing the somatotopic organization of trigeminal ganglion can help us to
improve the precision of treatment for trigeminal neuralgia. The distribution of
primary afferent perikarya of 3 branches of trigeminal nerve in the trigeminal
ganglion was investigated in the rabbit, and 3D model was reconstructed then.
After application of wheat germ agglutinin-horseradish peroxidase and DiI to the
cut endings of the 3 branches of trigeminal nerve, ophthalmic cells were found in
the anteromedial part of the trigeminal ganglion, mandibular cells in the
posterolateral part, and maxillary cells in the middle part. The results suggest
that the somatotopic organization of the ganglion in rabbits is a mediolateral
direction reflecting the mediolateral order of the ophthalmic, maxillary, and
mandibular nerves.
PMID- 25119407
TI - Intraoperative high-dose epinephrine infiltration in cleft palate repair.
PMID- 25119409
TI - Effective treatment of congenital muscular torticollis using botulinum toxin.
PMID- 25119410
TI - India: reverse innovation and the dichotomy of medical resources.
PMID- 25119411
TI - Treatment of large calvarial defects with bone transport osteogenesis: a
preclinical sheep model.
AB - BACKGROUND: Bone transport osteogenesis (BTO), distraction of a free portion of
bone across a defect, offers an autologous solution to large cranial defects that
may allow treatment without permanent hardware implantation. This study
establishes a sheep model to evaluate the feasibility and distraction kinetics of
BTO. METHODS: Subtotal cranial defects (3.5 * 3.5 cm) were created in 10 young
adult sheep and a transport segment (3.5 * 2 cm) traversed the defect at varying
distraction rates (0, 0.5, 1.0, and 1.5 mm/day) using semi-buried cranial
distractors. After a 6-week consolidation period, sheep were euthanized and the
resultant bone was analyzed by CT, histology, and mechanical testing. RESULTS:
Gross examination, histology, and 3D CT revealed that control animals had fibrous
nonunion whereas distraction animals had ossified defects with fibrous nonunion
at the distal docking site. There was one premature consolidation in the 0.5
mm/day group. The volume of bony regenerate in the 0.5, 1.0, and 1.5 mm/day
distraction rate groups was statistically indistinct (P = 0.16). The mean
flexural moduli (MPa) of non-decalcified samples from the control cranium,
transport segment, and bone regenerate were found to be 4.50 +/- 4.9, 6.17 +/-
2.1, and 4.14 +/- 4.8, respectively (P = 0.24). CONCLUSIONS: This experiment
provides proof of concept for BTO for large calvarial defects in a sheep model.
Distraction at a rate of 0.5 mm per day may place individuals at higher risk for
premature consolidation, but distraction rates did not have significant effects
on regenerate quantity or quality. Future work will include the use of
curvilinear distraction devices for 3-dimensional contour.
PMID- 25119412
TI - Osteochondroma of the mandibular condyle: a classification system based on
computed tomographic appearances.
AB - OBJECTIVE: The objectives of this study were to introduce the classification of
osteochondroma of the mandibular condyle based on computed tomographic images and
to present our treatment experiences. MATERIALS AND METHODS: From January 2002
and December 2012, a total of 61 patients with condylar osteochondroma were
treated in our division. Both clinical and radiologic aspects were reviewed. The
average follow-up period was 24.3 months with a range of 6 to 120 months.
RESULTS: Two types of condylar osteochondroma were presented: type 1 (protruding
expansion) in 50 patients (82.0%) and type 2 (globular expansion) in 11 patients
(18.0%). Type 1 condylar osteochondroma presented 5 forms: anterior/anteromedial
(58%), posterior/posteromedial (6%), medial (16%), lateral (6%), and gigantic
(14%). Local resection was performed on patients with type 1 condylar
osteochondroma. Subtotal condylectomy/total condylectomy using costochondral
graft reconstruction with/without orthognathic surgeries was performed on
patients with type 2 condylar osteochondroma. During the follow-up period, tumor
reformation, condyle absorption, and new deformity were not detected. The
patients almost reattained facial symmetry. CONCLUSIONS: Preoperative
classification based on computed tomographic images will help surgeons to choose
the suitable surgical procedure to treat the condylar osteochondroma.
PMID- 25119413
TI - Analysis of therapeutic effect of microvascular decompression surgery on
idiopathic hemifacial spasm.
AB - OBJECTIVE: The objective of this paper is to study the therapeutic effect of
microvascular decompression surgery on idiopathic hemifacial spasm with
compression on different zones of facial nerve. METHODS: The clinical data of 348
patients with idiopathic hemifacial spasm treated by microvascular decompression
surgery were retrospectively analyzed. Patients were divided into 5 groups
according to compression on different zones of facial nerve by offending vessels.
Root exit point was compressed in 18 patients (group A), transitional zone of
brainstem was compressed in 42 patients (group B), attached segment of brainstem
was compressed in 35 patients (group C), distal cisternal portion was compressed
in 21 patients (group D), and 2 or more zones were compressed in 232 patients
(group E). The therapeutic effect was observed, and outcome of excellent and
partial good were regarded as effective. RESULTS: Patients were followed up for
0.5 to 2 years. The effective rates were 94.4%, 95.2%, 97.1%, 95.2%, and 93.9% in
group A, group B, group C, group D, and group E, respectively.No death occurred
during operation,and there were no severe complications such as complete facial
paralysis, intracranial hematoma, and hearing loss after operation. CONCLUSION:
Microvascular decompression surgery is the first choice for treatment hemifacial
spasm. Proper detection of offending vessels and complete decompression may be
the key factors to increase the cure rate.
PMID- 25119414
TI - Appraisal of efficacy and safety of intralesional injection of high concentration
of bleomycin A5 for treatment of huge macrocystic lymphatic malformations in
cervical region.
AB - The objective of this study was to investigate the therapeutic effects and safety
of intralesional injection of high concentration of bleomycin A5 for huge (more
than 5 cm in diameter) macrocystic lymphatic malformations (LMs) in the cervical
region. Thirty-two patients with huge macrocystic LMs were treated with
percutaneous injection of bleomycin A5 in our department between 2006 and 2011.
Among them, 13 patients had unilateral submandibular lesions, and 19 patients had
lesions in anterior cervical regions. The age of patients ranged from 10 months
to 29 years (mean age, 11.4 y). The concentration of the drug was as high as 2.7
mg/mL (8 mg/3 mL) with an addition of dexamethasone. The mean sessions of
injection were 1.6 (1-3 sessions). Repeated injection interval was 4 to 6 weeks.
The follow-up period was 6 months to 4 years after the last treatment, and the
mean follow-up time was 18 months. The results were evaluated based on clinical
examination and Doppler ultrasonography scan. The clinical follow-up showed
excellent response in 28 of the 32 patients, whereas 4 of the 32 patients also
had a satisfactory response. No serious complications were encountered.
Intralesional injection of high concentration of bleomycin A5 was an effective
and safe treatment of huge macrocystic LMs in the cervical region and can obtain
satisfactory results esthetically and functionally without surgery.
PMID- 25119415
TI - How many theories on the genetic code do we need?
PMID- 25119416
TI - Evidence of three-level trophic transfer of quantum dots in an aquatic food chain
by using bioimaging.
AB - In this study, we demonstrated the three-level trophic transfer of quantum dots
(QDs) within the aquatic food chain. Using bioimaging, we observed QD transfer
from protozoa (Astasia longa) to zooplankton (Moina macrocopa) to fish (Danio
rerio). Bioimaging is an effective tool that can improve our understanding of the
delivery of nanomaterials in vivo. Measurement with an intravital multiphoton
laser scanning microscope visually proved the transfer of QDs from the first to
the second and the second to the third levels. As QDs may be passed from lower
organisms to humans via the food chain, our findings have implications for the
safety of their use.
PMID- 25119418
TI - Utility of models of the gastrointestinal tract for assessment of the digestion
and absorption of engineered nanomaterials released from food matrices.
AB - Engineered metal/mineral, lipid and biochemical macromolecule nanomaterials (NMs)
have potential applications in food. Methodologies for the assessment of NM
digestion and bioavailability in the gastrointestinal tract are nascent and
require refinement. A working group was tasked by the International Life Sciences
Institute NanoRelease Food Additive project to review existing models of the
gastrointestinal tract in health and disease, and the utility of these models for
the assessment of the uptake of NMs intended for food. Gastrointestinal digestion
and absorption could be addressed in a tiered approach using in silico
computational models, in vitro non-cellular fluid systems and in vitro cell
culture models, after which the necessity of ex vivo organ culture and in vivo
animal studies can be considered. Examples of NM quantification in
gastrointestinal tract fluids and tissues are emerging; however, few standardized
analytical techniques are available. Coupling of these techniques to
gastrointestinal models, along with further standardization, will further
strengthen methodologies for risk assessment.
PMID- 25119417
TI - Toxic responses in rat embryonic cells to silver nanoparticles and released
silver ions as analyzed via gene expression profiles and transmission electron
microscopy.
AB - After exposing rat embryonic cells to 20 MUg/mL of silver nanoparticle (NP)
suspension and their released ions for different time periods, silver
nanoparticles were found in cellular nuclei, mitochondria, cytoplasm and
lysosomes by transmission electron microscopy (TEM). We also observed
mitochondrial destruction, distension of endoplasmic reticulum and apoptotic
bodies. Global gene expression analysis showed a total of 279 genes that were up
regulated and 389 genes that were down-regulated in the silver-NP suspension
exposure group, while 3 genes were up-regulated and 41 genes were down-regulated
in the silver ion exposure group. Further, the GO pathway analysis suggested that
these differentially expressed genes are involved in several biological
processes, such as energy metabolism, oxygen transport, enzyme activities,
molecular binding, etc. It is possible that inhibition of oxygen transport is
mediated by the significant down-regulation of genes of the globin family, which
might play an important role in silver ion-induced toxicity. KEGG pathway
analysis showed that there were 23 signal pathways that were affected in the
cells after exposure to silver-NP suspension, but not silver ion alone. The most
significant change concerned inflammatory signal pathways, which were only found
in silver-NP suspension exposed cells, indicating that inflammatory response
might play an important role in the mechanism(s) of silver-NP-induced toxicity.
The significant up-regulation of matrix metalloproteinases 3 and 9 suggests that
silver NPs could induce extracellular matrix degradation via an inflammatory
signaling pathway. The significant up-regulation of secretory leukocyte peptidase
inhibitor and serine protease inhibitor 2c was considered to be an embryonic
cellular defense mechanism in response to silver-NP-induced inflammation.
PMID- 25119419
TI - Optimising the use of commercial LAL assays for the analysis of endotoxin
contamination in metal colloids and metal oxide nanoparticles.
AB - Engineered nanoparticles (NP) are generally contaminated by bacterial endotoxin,
a ubiquitous bacterial molecule with significant toxic and inflammatory effects.
The presence of endotoxin, if not recognised, can be responsible for many of the
in vitro and in vivo effects attributed to NPs. The Limulus Amoebocyte Lysate
(LAL) assay, the test requested by regulatory authorities for assessing endotoxin
contamination in products for human use, is not immediately applicable for
testing endotoxin in NP preparations, mainly due to the possible interference of
NPs with the assay readouts and components. In this study, we have compared
different commercially available LAL assays for detecting endotoxin in gold,
silver and iron oxide NPs. Different NP chemistry, concentrations and surface
coatings could differently interfere with the LAL assays' results. After accurate
testing of the possible interaction/interference of NPs with the various assay
components, the modified chromogenic LAL assay proved the most suitable assay for
measuring endotoxin in NP samples, provided the appropriate controls are
performed. Thus, endotoxin determination can be performed in NP preparation with
commercial LAL assays only after assay validation, i.e. once possible
interference of NPs with the assay components and readouts has been excluded.
PMID- 25119420
TI - Problem gambling subtypes based on psychological distress, alcohol abuse and
impulsivity.
AB - The notion of comorbidities within problem gambling populations has important
clinical implications, particularly for appropriate treatment matching. The
comorbidities most commonly cited in problem gambling literature include
depression, anxiety, alcohol abuse and impulsivity. Previous research shows
evidence of patterns in multiple co-occurring comorbidities and that there may be
different subtypes of gamblers based on these patterns. To further the current
understanding of gambling subtypes, the aim of our study was to identify subtypes
of gamblers currently in treatment. Hierarchical Cluster Analysis yielded four
mutually exclusive groups of 202 gamblers: (1) gamblers with comorbid
psychological problems (35%); (2) 'pure' gamblers without other comorbidities
(27%); (3) gamblers with comorbid alcohol abuse (25%); and (4) 'multimorbid'
gamblers (13%). The four groups differed on demographic information, drug use and
gambling behaviours including gambling activity and problem gambling severity.
Gamblers with comorbid psychological problems were more likely to be older women
on low income, more likely to report a family history of psychological problems
and were more often electronic gaming machine players. As expected, 'pure'
gamblers had lower problem gambling severity and were more likely to report
current abstinence. Gamblers with comorbid alcohol abuse were more likely to be
young men who used stimulant drugs, endorsed a higher quality of life and worked
full-time. 'Multimorbid' gamblers were elevated on all comorbidities, had general
problems related to their health and wellbeing and reported high rates of
hostility and aggression. These groups combine elements of existing conceptual
models of gambling subtypes and may require different treatments.
PMID- 25119422
TI - Targeting IgE to facilitate oral immunotherapy for food allergy: a potential new
role for anti-IgE therapy?
AB - Food allergy is a major public health problem without satisfactory treatment
options. Of several new treatments being studied, oral immunotherapy (OIT)
appears to be the most promising. Unfortunately, OIT is associated with an
unacceptably high frequency of allergic reactions. However, recent studies
suggest that OIT might be made safer and faster when performed in conjunction
with anti-IgE monoclonal antibody as an adjunctive treatment.
PMID- 25119421
TI - Cannabis-related impairment: the impacts of social anxiety and misconceptions of
friends' cannabis-related problems.
AB - OBJECTIVE: Socially anxious cannabis users are especially vulnerable to cannabis
related impairment, yet mechanisms underlying this vulnerability remain unclear.
Socially anxious persons may use cannabis despite related problems if they
believe such problems are common, and thus socially acceptable. Yet no known
studies have examined the impact of beliefs regarding others' cannabis-related
problems on one's own use-related problems. METHOD: This study investigated the
impact of beliefs about a close friend's experience with cannabis-related
problems on the relationship between social anxiety and cannabis-related
problems. The sample consisted of 158 (75% female) current (past-month) cannabis
using undergraduates. RESULTS: Believing one's friend experienced more cannabis
problems was related to experiencing more cannabis-related problems oneself. In
fact, perceived friend's problems accounted for 40% of the unique variance in
one's own cannabis problems. Descriptive norms (others' use) and injunctive norms
(others' approval of risky use) were unrelated to the number of one's own
problems. Social anxiety was related to experiencing more cannabis problems. This
relation was moderated by perceived friend's problems such that greater social
anxiety was related to more cannabis-related problems among participants who
believed their friend experienced more cannabis-related problems. This was not
the case among participants who believed their friend experienced fewer problems.
CONCLUSIONS: Normative beliefs regarding a close friend's cannabis problems were
robustly and uniquely related to experiencing more cannabis-related impairment.
Beliefs regarding friends' experience with cannabis-related problems may play an
especially important role in the experience of cannabis-related problems among
socially anxious users.
PMID- 25119423
TI - Steroid withdrawal in kidney allograft recipients.
AB - This review highlights the aggregate of knowledge obtained from the temporal
trend of kidney transplant immune suppression. We will discuss the burden of
steroid side effects and their impact on quality of life in kidney allograft
recipients, which have led to minimizing steroid exposure. Issues arising since
the inception of the concept of steroid withdrawal will be discussed, along with
how they have continually led to a shift in research focus on this subject
matter. The usefulness of surveillance biopsies and how further elucidation of
the pathophysiology of interstitial fibrosis and tubular atrophy could contribute
to improving long-term allograft outcomes will also be discussed. We will
elaborate on the role of calcineurin inhibitor minimization alongside steroid
withdrawal in improving long-term graft survival. Future expectations of
subsequent studies with a view to improving overall kidney allograft outcomes by
eliminating attendant problems associated with steroids will also be covered.
PMID- 25119426
TI - Structure, stability and photocatalytic H2 production by Cr-, Mn-, Fe-, Co-, and
Ni-substituted decaniobate clusters.
AB - Here we report synthesis and characterization of early transition-metal(TM)
substituted decaniobates as a continuation of our previous report of
tetramethylammonium (TMA) salt of FeNb9 and NiNb9: TMA6[H2Cr(III)Nb9O28].14H2O
(1, CrNb9), TMA8[Mn(III)Nb9O28].29H2O (2, MnNb9) and TMA7[H2Co(II)Nb9O28].25H2O
(3, CoNb9). Among the TM-substituted decaniobates, CoNb9 or NiNb9 exhibit a
higher photocatalytic H2 evolution activity in methanol-water mixtures than
others.
PMID- 25119425
TI - The effect of the cation alkyl chain branching on mutual solubilities with water
and toxicities.
AB - The design of ionic liquids has been focused on the cation-anion combinations but
other more subtle approaches can be used. In this work the effect of the
branching of the cation alkyl chain on the design of ionic liquids (ILs) is
evaluated. The mutual solubilities with water and toxicities of a series of
bis(trifluoromethylsulfonyl)-based ILs, combined with imidazolium, pyridinium,
pyrrolidinium, and piperidinium cations with linear or branched alkyl chains, are
reported. The mutual solubility measurements were carried out in the temperature
range from (288.15 to 323.15) K. From the obtained experimental data, the
thermodynamic properties of the solution (in the water-rich phase) were
determined and discussed. The COnductor like Screening MOdel for Real Solvents
(COSMO-RS) was used to predict the liquid-liquid equilibrium. Furthermore,
molecular dynamic simulations were also carried out aiming to get a deeper
understanding of these fluids at the molecular level. The results show that the
increase in the number of atoms at the cation ring (from five to six) leads to a
decrease in the mutual solubilities with water while increasing their toxicity,
and as expected from the well-established relationship between toxicities and
hydrophobicities of ILs. The branching of the alkyl chain was observed to
decrease the water solubility in ILs, while increasing the ILs solubility in
water. The inability of COSMO-RS to correctly predict the effect of branching
alkyl chains toward water solubility on them was confirmed using molecular
dynamic simulations to be due to the formation of nano-segregated structures of
the ILs that are not taken into account by the COSMO-RS model. In addition, the
impact of branched alkyl chains on the toxicity is shown to be not trivial and to
depend on the aromatic nature of the ILs.
PMID- 25119424
TI - Nitroso Diels-Alder (NDA) reaction as an efficient tool for the functionalization
of diene-containing natural products.
AB - This review describes the use of nitroso Diels-Alder reactions for the
functionalization of complex diene-containing natural products in order to
generate libraries of compounds with potential biological activity. The
application of this methodology to the structural modification of a series of
natural products (thebaine, steroidal dienes, rapamycin, leucomycin, colchicine,
isocolchicine and piperine) is discussed using relevant examples from the
literature from 1973 onwards. The biological activity of the resulting compounds
is also discussed. Additional comments are provided that evaluate the methodology
as a useful tool in organic, bioorganic and medicinal chemistry.
PMID- 25119428
TI - The relationship between electronic nursing care reminders and missed nursing
care.
AB - The purpose of the study was to explore relationships between nurses' perceptions
of the impact of health information technology on their clinical practice in the
acute care setting, their use of electronic nursing care reminders, and episodes
of missed nursing care. The study aims were accomplished with a descriptive
design using adjusted correlations. A convenience sample (N = 165) of medical
and/or surgical, intensive care, and intermediate care RNs working on acute care
hospital units participated in the study. Nurses from 19 eligible nursing units
were invited to participate. Adjusted relationships using hierarchical multiple
regression analyses indicated significant negative relationships between missed
nursing care and nursing care reminders and perceptions of health information
technology. The adjusted correlations support the hypotheses that there is a
relationship between nursing care reminder usage and missed nursing care and a
relationship between health information technology and missed nursing care. The
relationships are negative, indicating that nurses who rate higher levels of
reminder usage and health information technology have decreased reports of missed
nursing care. The study found a significant relationship between nursing care
reminders usage and decreased amounts of missed nursing care. The findings can be
used in a variety of improvement endeavors, such as encouraging nurses to utilize
nursing care reminders, aid information system designers when designing nursing
care reminders, and assist healthcare organizations in assessing the impact of
technology on nursing practice.
PMID- 25119427
TI - GATA6 loss-of-function mutations contribute to familial dilated cardiomyopathy.
AB - Dilated cardiomyopathy (DCM), the most prevalent form of primary heart muscle
disease, is the third most common cause of heart failure and the most frequent
reason for cardiac transplantation. Mounting evidence has demonstrated that
genetic risk factors are crucial in the pathogenesis of DCM. However, DCM is
genetically heterogeneous, and the genetic basis of DCM in a large majority of
cases remains unclear. In the current study, the coding exons and flanking
introns of the GATA6 gene, which encodes a zinc-finger transcription factor
essential for cardiogenesis, was sequenced in 140 unrelated patients with DCM,
and two novel heterozygous mutations, p.C447Y and p.H475R, were identified in two
index patients with DCM, respectively. Analysis of the pedigrees showed that in
each family the mutation co-segregated with DCM transmitted in an autosomal
dominant pattern, with complete penetrance. The missense mutations were absent in
400 control chromosomes and predicted to be disease-causing by MutationTaster or
probably damaging by PolyPhen-2. The alignment of multiple GATA6 proteins across
species revealed that the altered amino acids were completely conserved
evolutionarily. The functional assays showed that the mutated GATA6 proteins were
associated with significantly reduced transcriptional activation in comparison
with their wild-type counterpart. To the best of our knowledge, this is the first
study on the association of GATA6 loss-of-function mutations with enhanced
susceptibility to familial DCM, which provides novel insight into the molecular
mechanism of DCM and suggests potential implications for the antenatal
prophylaxis and allele-specific treatment of DCM.
PMID- 25119430
TI - Dual changes in conformation and optical properties of fluorophores within a
metal-organic framework during framework construction and associated sensing
event.
AB - Microsized chemosensor particle (CPP-16, CPP means coordination polymer
particle), which is made from a metal-organic framework (MOF), is synthesized
using pyrene-functionalized organic building block. This building block contains
three important parts, a framework construction part, a Cu(2+) detection part,
and a fluorophore part. PXRD studies have revealed that CPP-16 has a 3D cubic
structure of MOF-5. During both MOF formation and sensing event, fluorophores
within CPP-16 undergo dual changes in conformation and optical properties. After
MOF construction, pyrene moieties experience an unusual complete conversion from
monomer to excimer form. This conversion takes place due to a confinement effect
induced by space limitations within the MOF structure. The selective sensing
ability of CPP-16 on Cu(2+) over many other metal ions is verified by emission
spectra and is also visually identified by fluorescence microscopy images.
Specific interaction of Cu(2+) with binding sites within CPP-16 causes a second
conformational change of the fluorophores, where they change from stacked excimer
(CPP-16) to quenched excimer states (CPP-16.Cu(2+)).
PMID- 25119431
TI - A general diastereoselective catalytic vinylogous aldol reaction among tetramic
acid-derived pyrroles.
AB - A catalytic diastereoselective aldol reaction has been developed for N1
arylated/C2-O-silylated/C3-methylated and brominated/C4-O-methylated pyrroles in
its reactions with various aldehydes. Syn adducts emerge with regard to the
vicinal nitrogen and oxygen heteroatom substituents. The N1-aryl residue
undergoes oxidative cleavage, and the C3-bromine atom undergoes palladium
mediated coupling reactions, both without disturbing the newly created
stereocenters.
PMID- 25119429
TI - CCR5 controls immune and metabolic functions during Toxoplasma gondii infection.
AB - CCR5, an important receptor related to cell recruitment and inflammation, is
expressed during experimental Toxoplasma gondii infection. However, its role in
the immunopathology of toxoplasmosis is not clearly defined yet. Thus, we
inoculated WT and CCR5(-/-) mice with a sub lethal dose of the parasite by oral
route. CCR5(-/-) mice were extremely susceptible to infection, presenting higher
parasite load and lower tissue expression of IL-12p40, IFN-gamma, TNF, IL-6,
iNOS, Foxp3, T-bet, GATA-3 and PPARalpha. Although both groups presented
inflammation in the liver with prominent neutrophil infiltration, CCR5(-/-) mice
had extensive tissue damage with hepatocyte vacuolization, steatosis, elevated
serum triglycerides and transaminases. PPARalpha agonist Gemfibrozil improved the
vacuolization but did not rescue CCR5(-/-) infected mice from high serum
triglycerides levels and enhanced mortality. We also found intense inflammation
in the ileum of CCR5(-/-) infected mice, with epithelial ulceration, augmented
CD4 and decreased frequency of NK cells in the gut lamina propria. Most
interestingly, these findings were accompanied by an outstanding accumulation of
neutrophils in the ileum, which seemed to be involved in the gut immunopathology,
once the depletion of these cells was accompanied by reduced local damage.
Altogether, these data demonstrated that CCR5 is essential to the control of T.
gondii infection and to maintain the metabolic, hepatic and intestinal integrity.
These findings add novel information on the disease pathogenesis and may be
relevant for directing future approaches to the treatment of multi-deregulated
diseases.
PMID- 25119432
TI - Radical scavenging ability of gallic acid toward OH and OOH radicals. Reaction
mechanism and rate constants from the density functional theory.
AB - Gallic acid is a ubiquitous compound, widely distributed in the vegetal kingdom
and frequently found in the human diet. In the present work, its primary
antioxidant activity has been investigated using the density functional theory
(DFT), and the quantum mechanics-based test for overall free radical scavenging
activity (QM-ORSA) protocol. It was found that gallic acid is a better
antioxidant than the reference compound, Trolox, regardless of the polarity of
the environment. In addition, gallic acid is predicted to be among the best
peroxyl radical scavengers identified so far in nonpolar (lipid) media. This
compound is capable of scavenging hydroxyl radicals at diffusion-limited rates,
and hydroperoxyl radicals with rate constants in the order of 10(5) M(-1) s(-1).
The deprotonation of gallic acid, in aqueous solution, is predicted to increase
the protective action of this compound against oxidative stress. Gallic acid was
also identified as a versatile scavenger, capable of rapidly deactivating a wide
variety of reactive oxygen species (ROS) and reactive nitrogen species (RNS) via
electron transfer at physiological pH.
PMID- 25119435
TI - Abstracts from the ESP Meeting 2014.
PMID- 25119433
TI - Risk factors for linezolid-associated thrombocytopenia in adult patients.
AB - OBJECTIVES: Thrombocytopenia (TP) is a common adverse effect of linezolid (LZD).
However, risk factors for LZD-associated TP have been reported in Western
patients with relatively heavy body weight. The aim of this study was to
determine the risk factors for LZD-associated TP in Asian population. MATERIALS
AND METHODS: A retrospective cohort study was conducted among 101 consecutive
patients who received LZD therapy (1,200 mg/day) between July 2003 and December
2013 at a tertiary referral hospital in Tokyo, Japan. The patients with obvious
other causes for TP were excluded. The information of target infectious disease,
patients' age, gender, body weight, body mass index, baseline serum creatinine
(SCr), baseline platelet count, and treatment duration was collected
retrospectively. TP was defined as >= 50% decrease in platelet count from
baseline. Bi- and multi-variate analyses were performed. RESULTS: A total of 101
patients were included (mean age [SD] 64 [18]; male gender [%], 57 [56]). Median
duration [range] of LZD therapy was 14 days [1-67]. LZD-associated TP was
identified in 42 patients (42%). For TP, adjusted odds ratio (OR) [95% CI] of
daily per kg dose (DPKD) and SCr was 1.14 [1.05-1.26] and 1.51 [1.01-2.50],
respectively. CONCLUSIONS: Higher DPKD and elevated SCr are significantly
associated with LZD-associated TP. These findings suggest that daily dose of LZD
should be adjusted using body weight, as typically done in pediatrics, in adults
as well. Renal function also should be considered for dose adjustment.
PMID- 25119436
TI - Synthesis, structure, and magnetic and electrochemical properties of quasi-linear
and linear iron(I), cobalt(I), and nickel(I) amido complexes.
AB - Three potassium crown ether salts, [K(Et2O)2(18-crown-6)][Fe{N(SiMe3)Dipp}2] (1a;
Dipp = C6H3-2,6-Pr(i)2), [K(18-crown-6)][Fe{N(SiMe3)Dipp}2].0.5PhMe (1b), and
[K(18-crown-6)][M{N(SiMe3)Dipp}2] (M = Co, 2; M = Ni, 3), of the two-coordinate
linear or near-linear bis-amido monoanions [M{N(SiMe3)Dipp}2](-) (M = Fe, Co, Ni)
were synthesized by one-electron reduction of the neutral precursors
M{N(SiMe3)Dipp}2 with KC8 in the presence of 18-crown-6. They were characterized
by X-ray crystallography, UV-vis spectroscopy, cyclic voltammetry, and magnetic
measurements. The anions feature lengthened M-N bonds in comparison with their
neutral precursors, with slightly bent coordination (N-Fe-N = ca. 172 degrees )
for the iron(I) complex, but linear coordination for the cobalt(I) and nickel(I)
complexes. Fits of the temperature dependence of chiMT of 1 and 2 reveal that the
iron(I) and cobalt(I) complexes have large negative D zero-field splittings and a
substantial orbital contribution to their magnetic moments with L = 2, whereas
the nickel(I) complex has at most a small orbital contribution to its magnetic
moment. The magnetic results have been used to propose an ordering of the 3d
orbitals in each of the complexes.
PMID- 25119434
TI - Structural study of the RIPoptosome core reveals a helical assembly for kinase
recruitment.
AB - Receptor interaction protein kinase 1 (RIP1) is a molecular cell-fate switch.
RIP1, together with Fas-associated protein with death domain (FADD) and caspase
8, forms the RIPoptosome that activates apoptosis. RIP1 also associates with RIP3
to form the necrosome that triggers necroptosis. The RIPoptosome assembles
through interactions between the death domains (DDs) of RIP1 and FADD and between
death effector domains (DEDs) of FADD and caspase-8. In this study, we analyzed
the overall structure of the RIP1 DD/FADD DD complex, the core of the
RIPoptosome, by negative-stain electron microscopy and modeling. The results show
that RIP1 DD and FADD DD form a stable complex in vitro similar to the previously
described Fas DD/FADD DD complex, suggesting that the RIPoptosome and the Fas
death-inducing signaling complex share a common assembly mechanism. Both
complexes adopt a helical conformation that requires type I, II, and III
interactions between the death domains.
PMID- 25119439
TI - Echinocandin-induced eosinophilia: a case report.
AB - Drug-induced eosinophilia is difficult to diagnose. Severe organ damage can occur
if it is left untreated. Presently, caspofungin is the only echinocandin that has
been reported to cause eosinophilia. A patient who developed eosinophilia after
exposure to caspofungin and re-challenge with anidulafungin is presented.
Eosinophilia resolved upon discontinuation of both drugs.
PMID- 25119438
TI - Bmovo-1 regulates ovary size in the silkworm, Bombyx mori.
AB - The regulation of antagonistic OVO isoforms is critical for germline formation
and differentiation in Drosophila. However, little is known about genes related
to ovary development. In this study, we cloned the Bombyx mori ovo gene and
investigated its four alternatively spliced isoforms. BmOVO-1, BmOVO-2 and BmOVO
3 all had four C2H2 type zinc fingers, but differed at the N-terminal ends, while
BmOVO-4 had a single zinc finger. Bmovo-1, Bmovo-2 and Bmovo-4 showed the highest
levels of mRNA in ovaries, while Bmovo-3 was primarily expressed in testes. The
mRNA expression pattern suggested that Bmovo expression was related to ovary
development. RNAi and transgenic techniques were used to analyze the biological
function of Bmovo. The results showed that when the Bmovo gene was downregulated,
oviposition number decreased. Upregulation of Bmovo-1 in the gonads of transgenic
silkworms increased oviposition number and elevated the trehalose contents of
hemolymph and ovaries. We concluded that Bmovo-1 was involved in protein
synthesis, contributing to the development of ovaries and oviposition number in
silkworms.
PMID- 25119440
TI - Spleen enlargement is a common finding in acute Puumala hantavirus infection and
it does not associate with thrombocytopenia.
AB - The pathogenesis of thrombocytopenia in Puumala hantavirus (PUUV) infection is
probably multifactorial. We aimed to evaluate the possible spleen enlargement
during acute PUUV infection, and to determine its association with
thrombocytopenia and disease severity. Magnetic resonance imaging (MRI) of the
spleen was performed in 20 patients with acute PUUV infection. MRI was repeated 5
8 months later. The change in spleen length was compared with markers describing
the severity of the disease. In all patients, the spleen length was increased in
the acute phase compared with the control phase (median 129 mm vs 111 mm, p <
0.001). The change correlated with maximum C-reactive protein value (r = 0.513, p
= 0.021) and inversely with maximum leukocyte count (r = -0.471, p = 0.036), but
not with maximum serum creatinine level or minimum platelet count. Enlarged
spleen, evaluated by MRI, was shown to be a common finding during acute PUUV
infection. However, it does not associate with thrombocytopenia and acute kidney
injury.
PMID- 25119441
TI - Murine typhus in elderly patients: a prospective study of 49 patients.
AB - BACKGROUND: The characteristics of Rickettsia typhi infection in elderly patients
have not been extensively described in the literature. METHODS: We conducted a
prospective study on murine typhus in patients > 65 years old in two endemic
areas of Greece. RESULTS: Forty-nine elderly patients were analyzed, including 30
(61.2%) males. The clinical triad of fever (100% of patients), headache (83.7%),
and rash (73.5%), occurred in 63% of patients, whereas malaise (85.7%), anorexia
(65.3%), and myalgia (59.2%) were also common. Frequent laboratory findings were
transaminasemia (89.8%), lactate dehydrogenase elevation (65.3%), hematuria
(55.1%), thrombocytopenia (53.1%), anemia (51%), leucopenia (40.8%), and mild
hyponatremia (23.5%). Complications developed in 16 patients (32.7%); no deaths
were recorded. CONCLUSIONS: The main clinical and laboratory characteristics of
murine typhus are similar in elderly and younger adults. However, elderly
patients have a more severe clinical picture, evidenced by a higher complication
rate and longer duration of fever, even with appropriate treatment. To our
knowledge, this is the first study to focus on murine typhus in a geriatric
population.
PMID- 25119442
TI - NUNDO: a numerical model of a human torso phantom and its application to
effective dose equivalent calculations for astronauts at the ISS.
AB - The health effects of cosmic radiation on astronauts need to be precisely
quantified and controlled. This task is important not only in perspective of the
increasing human presence at the International Space Station (ISS), but also for
the preparation of safe human missions beyond low earth orbit. From a radiation
protection point of view, the baseline quantity for radiation risk assessment in
space is the effective dose equivalent. The present work reports the first
successful attempt of the experimental determination of the effective dose
equivalent in space, both for extra-vehicular activity (EVA) and intra-vehicular
activity (IVA). This was achieved using the anthropomorphic torso phantom
RANDO((r)) equipped with more than 6,000 passive thermoluminescent detectors and
plastic nuclear track detectors, which have been exposed to cosmic radiation
inside the European Space Agency MATROSHKA facility both outside and inside the
ISS. In order to calculate the effective dose equivalent, a numerical model of
the RANDO((r)) phantom, based on computer tomography scans of the actual phantom,
was developed. It was found that the effective dose equivalent rate during an EVA
approaches 700 MUSv/d, while during an IVA about 20 % lower values were observed.
It is shown that the individual dose based on a personal dosimeter reading for an
astronaut during IVA results in an overestimate of the effective dose equivalent
of about 15 %, whereas under an EVA conditions the overestimate is more than 200
%. A personal dosemeter can therefore deliver quite good exposure records during
IVA, but may overestimate the effective dose equivalent received during an EVA
considerably.
PMID- 25119444
TI - Growing dynamical facilitation on approaching the random pinning colloidal glass
transition.
AB - Despite decades of research, it remains to be established whether the
transformation of a liquid into a glass is fundamentally thermodynamic or dynamic
in origin. Although observations of growing length scales are consistent with
thermodynamic perspectives, the purely dynamic approach of the Dynamical
Facilitation (DF) theory lacks experimental support. Further, for vitrification
induced by randomly freezing a subset of particles in the liquid phase,
simulations support the existence of an underlying thermodynamic phase
transition, whereas the DF theory remains unexplored. Here, using video
microscopy and holographic optical tweezers, we show that DF in a colloidal glass
forming liquid grows with density as well as the fraction of pinned particles. In
addition, we observe that heterogeneous dynamics in the form of string-like
cooperative motion emerges naturally within the framework of facilitation. Our
findings suggest that a deeper understanding of the glass transition necessitates
an amalgamation of existing theoretical approaches.
PMID- 25119443
TI - The design and discovery of lixisenatide for the treatment of type 2 diabetes
mellitus.
AB - INTRODUCTION: Lixisenatide is a once-daily short-acting glucagon-like peptide-1
(GLP-1) receptor agonist (GLP-1RA) used in the treatment of type 2 diabetes
mellitus (T2DM). It is used in combination with oral antidiabetics and/or basal
insulin in patients inadequately controlled on these medications and who are
undergoing diet and lifestyle modification. GLP-1RAs glucose-dependently increase
insulin secretion, decrease glucagon secretion, and slow gastric emptying,
thereby improving glycemic control. GLP-1RAs are associated with body weight
benefits and low rates of hypoglycemia which are welcome in patients with T2DM.
AREAS COVERED: The authors describe the identification of GLP-1RAs as suitable
targets for modification with structure-inducing probe technology to improve
stability and resistance to proteolytic degradation. Clinical studies have
assessed lixisenatide across > 5000 patients as a monotherapy or add-on to a
variety of commonly used antidiabetic medications. These studies highlighted the
effects of lixisenatide on gastric emptying, explaining its particular
improvements in postprandial plasma glucose (PPG) excursions and underscoring its
efficacy in combination with insulin glargine. Lixisenatide was well tolerated,
with nausea and vomiting being the most frequently reported adverse events.
EXPERT OPINION: The once-daily administration of lixisenatide as well as its
substantial sustained effect on gastric emptying and, hence, PPG excursions are
all important features compared with the other GLP-1RAs. The combination of two
injectables, such as basal insulin to lower fasting plasma glucose and a GLP-1RA
that curtails PPG excursions, is clinically valuable and could differentiate
lixisenatide from other GLP-1RAs, especially from those continuously acting GLP
1RAs with little effect on gastric emptying and PPG excursions.
PMID- 25119446
TI - Breaking news....
PMID- 25119447
TI - Dysphagia and associated risk factors following extubation in cardiovascular
surgical patients.
AB - Following cardiovascular (CV) surgery, prolonged mechanical ventilation of >48 h
increases dysphagia frequency over tenfold: 51 % compared to 3-4 % across all
durations. Our primary objective was to identify dysphagia frequency following CV
surgery with respect to intubation duration. Our secondary objective was to
explore characteristics associated with dysphagia across the entire sample. Using
a retrospective design, we stratified all consecutive patients who underwent CV
surgery in 2009 at our institution into intubation duration groups defined a
priori: I (<= 12 h), II (>12 to <= 24 h), III (>24 to <= 48 h), and IV (>48 h).
Eligible patients were >18 years old who survived extubation following coronary
artery bypass alone or cardiac valve surgery. Patients who underwent tracheotomy
were excluded. Pre-, peri-, and postoperative patient variables were extracted
from a pre-existing database and medical charts by two blinded reviewers.
Disagreements were resolved by consensus. Across the entire sample, multivariable
logistic regression analysis determined independent predictors of dysphagia.
Across the entire sample, dysphagia frequency was 5.6 % (51/909) but varied by
group: I, 1 % (7/699); II, 8.2 % (11/134); III, 16.7 % (6/36); and IV, 67.5 %
(27/40). Across the entire sample, the independent predictors of dysphagia
included intubation duration in 12-h increments (p < 0.001; odds ratio [OR] 1.93,
95 % confidence interval [CI] 1.63-2.29) and age in 10-year increments (p =
0.004; OR 2.12, 95 % CI 1.27-3.52). Patients had a twofold increase in their odds
of developing dysphagia for every additional 12 h with endotracheal intubation
and for every additional decade in age. These patients should undergo post
extubation swallow assessments to minimize complications.
PMID- 25119448
TI - Water extracts from winery by-products as tobacco defense inducers.
AB - Water extracts from winery by-products exhibited significant plant defense
inducer properties. Experiments were conducted on three marc extracts containing
various amounts of polyphenols and anthocyanins. Infiltration of red, white and
seed grape marc extracts into tobacco leaves induced hypersensitive reaction-like
lesions with cell death evidenced by Evans Blue staining. The infiltration zones
and the surrounding areas revealed accumulation of autofluorescent compounds
under UV light. Leaf infiltration of the three winery by-product extracts induced
defense gene expression. The antimicrobial PR1, beta-1,3-glucanase PR2, and
chitinase PR3 target genes were upregulated locally in tobacco plants following
grape marc extract treatments. The osmotin PR5 transcripts accumulated as well in
red marc extract treated-tobacco leaves. Overall, the winery by-product extracts
elicited an array of plant defense responses making the grape residues a
potential use of high value compounds.
PMID- 25119449
TI - Effects of Cd, Co, Cu, Ni and Zn on asexual reproduction and early development of
the tropical sea anemone Aiptasia pulchella.
AB - Currently few studies present sub-lethal toxicity data for tropical marine
species, and there are no routine toxicity tests using marine cnidarians. The
symbiotic sea anemone Aiptasia pulchella has been identified as a useful species
for ecotoxicological risk assessment, and would provide a tropical marine
cnidarian representative. Chronic sub-lethal toxicity tests assessing the effects
of 28-day trace metal exposure on asexual reproduction in A. pulchella were
investigated, and concentration-dependant reductions in the number of offspring
that were produced were evident for all metal exposures. Metal concentration
estimates causing 50% reductions in the numbers of asexually-reproduced juveniles
after 28-day exposures (28-day effect concentrations 50%: EC50s) were 14 ug/L for
copper, 63 ug/L for zinc, 107 ug/L for cobalt, 145 ug/L for cadmium, and 369 ug/L
for nickel. Slightly higher 28-day EC50s of 16 ug/L for copper, 192 ug/L for
zinc, 172 ug/L for cobalt, 185 ug/L for cadmium, and 404 ug/L for nickel
exposures and were estimated based on reductions in the total number of live
developed and undeveloped offspring. These sensitive and chronic sub-lethal
toxicity estimates help fill the knowledge gap related to metal effects on
cnidarians over longer exposure periods, and this newly-developed bioassay may
provide a much needed tool for ecotoxicological risk assessment relevant to
tropical marine environments.
PMID- 25119450
TI - Environmental stressors can enhance the development of community tolerance to a
toxicant.
AB - Ecosystems are subject to a combination of recurring anthropogenic and natural
disturbances, such as climate change and pesticide exposure. Biological
communities are known to develop tolerance to recurring disturbances due to
successive changes at both the community and organismal levels. However,
information on how additional stressors may affect the development of such
community tolerance is scarce to date. We studied the influence of hydrological
disturbance on the reaction of zooplankton communities to repeated insecticide
pulses in outdoor microcosms. The communities were exposed to three successive
pulses of the insecticide esfenvalerate (0.03, 0.3, and 3 ug/L) and to the
gradual removal of water and its subsequent replacement over three cycles or to a
constant water level. Except at the highest esfenvalerate concentration, the
communities developed tolerance to the toxicant, as indicated by their decreasing
reaction to subsequent insecticide applications, and this development was
enhanced by hydrological disturbance. The pronounced decline of the key taxa
Daphnia spp. through the combined action of the two stressors was identified as
the main mechanism responsible for the increase in community tolerance under a
fluctuating water level. Under a constant water level, the abundance of Daphnia
spp. did not decrease significantly without the insecticide treatment, indicating
that other mechanisms were responsible for the observed community tolerance. The
present study shows that additional stressors can facilitate the development of
community tolerance and that such facilitation is propagated through community
level mechanisms.
PMID- 25119451
TI - The imaging feature in capsule endoscopy on Maffucci syndrome with intestinal
hemangioma.
PMID- 25119452
TI - Combined application of clip and endoloop for the prevention of postpolypectomy
complications in large pedunculated colonic polyps: a better choice.
PMID- 25119453
TI - Cancer screenee cohort study of the National Cancer Center in South Korea.
AB - The Cancer Screenee Cohort Study was first established in 2002 by the National
Cancer Center in South Korea to investigate all possible risk factors related to
cancers and to expand biological specimen banking for the development of
effective methodologies for cancer detection, diagnosis, and prevention. As of
July in 2014, total 41,105 participants were enrolled in this cohort. Data were
collected via questionnaire, clinical examination, cancer screening, and
biological specimen testing including blood, urine, and exfoliated cervical
cells. The highest incidence was found to be thyroid cancer, according to a
nested case-control study that was linked to the National Cancer Registry
information as of December 31, 2011. Case-control, cross-sectional, and cohort
studies have been published using these data since 2009. Diet and nutrition was
the most published topic, followed by genetics, hepatitis B virus and liver
cancer screening, methodologies, physical activity, obesity, metabolic syndrome,
smoking and alcohol consumption, and blood type. Evidence from the Cancer
Screenee Cohort Study is highly anticipated to reduce the burden of cancer in the
Korean population and aid in the detection, diagnosis, and prevention of cancer.
PMID- 25119454
TI - Prevalence and healthcare utilization of herpes zoster and postherpetic neuralgia
in South Korea: disparity among patients with different immune statuses.
AB - OBJECTIVES: Despite the clinical and epidemiological importance of herpes zoster
(HZ) and postherpetic neuralgia (PHN), their disease and economic burden related
to immune status has not been studied in South Korea. Our aim was to calculate
the prevalence and rate of healthcare utilization related to HZ and PHN among
Korean patients stratified by immune status. METHODS: This retrospective study
used the Health Insurance Review and Assessment Service National Patients Sample
(HIRA K-NPS) database, which includes all medical claims from January to December
2009 on a representative sample of the Korean population. HZ and PHN patients
aged >= 50 years were categorized into three groups by immune status: severely
immunocompromised group, moderately compromised group, and non-compromised group.
The prevalence, disease-related healthcare utilization, and medical costs were
compared across the three groups. RESULTS: We estimated that there were 312,136
HZ patients and 48,461 PHN patients >= 50 years in South Korea. The prevalence of
HZ and PHN was 18.54 and 2.88 per 1,000 persons, respectively, and increased with
deteriorating immune status. The number of outpatient visits and hospitalization
rate among HZ patients were highest in the severely immunocompromised group
(4.38% and 7.52%, respectively) and lowest in the non-compromised group (3.82%
and 4.08%, respectively). The average medical cost per patient in the severe
group was the highest (240 US dollars) and that of the non-compromised group was
the lowest (161 US dollars). No parameters were significantly different among
patients with PHN by immunity. CONCLUSIONS: HZ patients with severe
immunodeficiency had a higher prevalence of HZ, more outpatient visits and
hospitalizations, longer hospitalizations, and higher medical costs than their
counterparts did. Efforts should be made to reduce the HZ-related burden of
severely immunocompromised patients.
PMID- 25119455
TI - Atrial fibrillation in end stage renal disease patients: influence of
hemodialysis on P wave duration and atrial dimension.
AB - BACKGROUND: Prevalence and incidence of atrial fibrillation (AF) are high in
hemodialysis (HD) patients. Intra-atrial conduction velocity slowing plays an
important role in AF onset. The aim of our study was to measure P wave duration
(Pwd), expression of intra-atrial conduction velocity, in HD patients with and
without a history of AF. METHODS: The study was performed in 47 end stage renal
disease (ESRD) patients, subdivided into four groups: 19 patients within the
first 6 months from starting HD therapy (HD1); the same patients studied 18 +/- 3
months later (HD2); patients with no history of AF and long dialytic age (HD3, n
= 13); and patients with sinus rhythm but history of AF (HDAF, n = 15); and 18
healthy controls. In all patients P wave high resolution recording and
electrolyte plasma values were obtained before and after a HD session, and atrial
diameter was assessed by echocardiography. RESULTS: Patients with the shortest
dialysis vintage showed the shortest Pwd [131.2 +/- 11.0 (HD1) vs. 139.8 +/- 11.7
(HD2), 142.1 +/- 7.2 (HD3), 152.3 +/- 15.0 (HDAF) ms; p < 0.05], while Pwd was
prolonged in patients with AF history when compared to all other groups (p <
0.03). At multivariate analysis atrial dimension was independently related to Pwd
(R = 0.40, p < 0.02). HD session induced a significant increase of Pwd (141 +/-
14.0-152 +/- 17.0 ms, p < 0.001), that was correlated to modifications of K(+)
concentration (R = 0.8, p < 0.0001). CONCLUSIONS: HD therapy prolongs Pwd. HD
patients with a history of AF have prolonged Pwd compared to patients without,
suggesting that increased Pwd is a marker of AF risk in patients with ESRD. HD
session acutely increases Pwd, creating conditions favoring AF onset.
PMID- 25119456
TI - Central administration of C-X-C chemokine receptor type 4 antagonist alleviates
the development and maintenance of peripheral neuropathic pain in mice.
AB - AIM: To explore the roles of C-X-C chemokine receptor type 4 (CXCR4) in spinal
processing of neuropathic pain at the central nervous system (CNS). METHODS:
Peripheral neuropathic pain (PNP) induced by partial sciatic nerve ligation
(pSNL) model was assessed in mice. Effects of a single intrathecal (central)
administration of AMD3100 (intrathecal AMD3100), a CXCR4 antagonist, on pain
behavior and pain-related spinal pathways and molecules in the L3-L5 spinal cord
segment was studied compare to saline treatment. RESULTS: Rotarod test showed
that intrathecal AMD3100 did not impair mice motor function. In pSNL-induced
mice, intrathecal AMD3100 delayed the development of mechanical allodynia and
reversed the established mechanical allodynia in a dose-dependent way. Moreover,
intrathecal AMD3100 downregulated the activation of JNK1 and p38 pathways and the
protein expression of p65 as assessed by western blotting. Real-time PCR test
also demonstrated that substance P mRNA was decreased, while adrenomedullin and
intercellular adhesion molecule mRNA was increased following AMD3100 treatment.
CONCLUSION: Our results suggest that central (spinal) CXCR4 is involved in the
development and maintenance of PNP and the regulation of multiple spinal
molecular events under pain condition, implicating that CXCR4 would potentially
be a therapeutic target for chronic neuropathic pain.
PMID- 25119458
TI - A commentary on the disparate perspectives of clinical microbiologists and
surgeons: Ad hoc antimicrobial use.
AB - Prosthetic joints and other orthopedic implants have improved quality of life for
patients world-wide and the use of such devices is increasing. However, while
infection rates subsequent to associated surgery are relatively low (<3%), the
consequences of incidence are considerable, encompassing morbidity (including
amputation) and mortality in addition to significant social and economic costs.
Emphasis, therefore, has been placed on mitigating microbial risk, with clinical
microbiologists and surgeons utilizing rapidly evolving molecular laboratory
techniques in detection and diagnosis of infection, which still occurs despite
sophisticated patient management. Multidisciplinary approaches are regularly
adopted to achieve this. In this commentary, we describe an unusual case of
Actinomyces infection in total hip arthroplasty and, in that context, describe
the perspectives of the clinical microbiology and surgical teams and how they
contrasted. More specifically, this case demonstrates an ad hoc approach to
structured eradication of biofilms and intracellular bacteria related to
biomaterials, as reflected in early usage of linezolid. This is a complex topic
and, as described in this case, such accelerated treatment can be effective. This
commentary focuses on the merits of such inadvisable use of potent antimicrobials
amid the risk of diminishing valuable antimicrobial efficacy, albeit resulting in
desirable patient outcomes.
PMID- 25119457
TI - Low-level laser irradiation improves functional recovery and nerve regeneration
in sciatic nerve crush rat injury model.
AB - The development of noninvasive approaches to facilitate the regeneration of post
traumatic nerve injury is important for clinical rehabilitation. In this study,
we investigated the effective dose of noninvasive 808-nm low-level laser therapy
(LLLT) on sciatic nerve crush rat injury model. Thirty-six male Sprague Dawley
rats were divided into 6 experimental groups: a normal group with or without 808
nm LLLT at 8 J/cm(2) and a sciatic nerve crush injury group with or without 808
nm LLLT at 3, 8 or 15 J/cm(2). Rats were given consecutive transcutaneous LLLT at
the crush site and sacrificed 20 days after the crush injury. Functional
assessments of nerve regeneration were analyzed using the sciatic functional
index (SFI) and hindlimb range of motion (ROM). Nerve regeneration was
investigated by measuring the myelin sheath thickness of the sciatic nerve using
transmission electron microscopy (TEM) and by analyzing the expression of growth
associated protein 43 (GAP43) in sciatic nerve using western blot and
immunofluorescence staining. We found that sciatic-injured rats that were
irradiated with LLLT at both 3 and 8 J/cm(2) had significantly improved SFI but
that a significant improvement of ROM was only found in rats with LLLT at 8
J/cm(2). Furthermore, the myelin sheath thickness and GAP43 expression levels
were significantly enhanced in sciatic nerve-crushed rats receiving 808-nm LLLT
at 3 and 8 J/cm(2). Taken together, these results suggest that 808-nm LLLT at a
low energy density (3 J/cm(2) and 8 J/cm(2)) is capable of enhancing sciatic
nerve regeneration following a crush injury.
PMID- 25119463
TI - Does minimally-invasive pancreaticoduodenectomy have advantages over its open
method? A meta-analysis of retrospective studies.
AB - BACKGROUND: While more and more open procedures now routinely performed using
laparoscopy, minimally invasive pancreaticoduodenectomy (MIPD) remains one of the
most challenging abdominal procedures. Therefore, we carried out this meta
analysis to evaluate whether MIPD is safe, feasible and worthwhile. METHODS:
PubMed, EMBASE, and Cochrane Library were searched to identify studies published
between January 1994 and November 2013 comparing MIPD with open
pancreaticoduodenectomy (OPD). Intraoperative outcomes, oncologic safety,
postoperative complications, and postoperative recovery were evaluated. RESULTS:
11 retrospective studies representing 869 patients (327 MIPDs, 542 OPDs) were
included. MIPD was associated with a reduction in estimated blood loss (MD
361.93 ml, 95% CI -519.22 to -204.63 ml, p<0.001, I(2) = 94%), wound infection
(OR 0.41, 95% CI 0.22 to 0.78, p = 0.007, I(2) = 0%), and hospital stay (MD -2.64
d, 95% CI -4.23 to -1.05 d, p = 0.001, I(2) = 78%). However, it brings longer
operative time (MD 105 min, 95% CI 49.73 to 160.26 min, p<0.001, I(2) = 93%).
There were no significant differences between the two procedures in likelihood of
overall complications (p = 0.05), pancreatic fistula (PF) (p = 0.86), delayed
gastric empting (DGE) (p = 0.96), positive surgical margins (p = 0.07), retrieval
of lymph nodes (p = 0.48), reoperation (p = 0.16) and mortality (p = 0.64).
CONCLUSIONS: Our results suggest that MIPD is currently safe, feasible and
worthwhile. But considering the selection bias, complexity of MIPD and lack of
long-term oncologic outcomes, we suggest it be performed in a high-volume
pancreatic surgery center in selected patients.
PMID- 25119464
TI - The pattern and loci of training-induced brain changes in healthy older adults
are predicted by the nature of the intervention.
AB - There is enormous interest in designing training methods for reducing cognitive
decline in healthy older adults. Because it is impaired with aging, multitasking
has often been targeted and has been shown to be malleable with appropriate
training. Investigating the effects of cognitive training on functional brain
activation might provide critical indication regarding the mechanisms that
underlie those positive effects, as well as provide models for selecting
appropriate training methods. The few studies that have looked at brain
correlates of cognitive training indicate a variable pattern and location of
brain changes--a result that might relate to differences in training formats. The
goal of this study was to measure the neural substrates as a function of whether
divided attentional training programs induced the use of alternative processes or
whether it relied on repeated practice. Forty-eight older adults were randomly
allocated to one of three training programs. In the single repeated training,
participants practiced an alphanumeric equation and a visual detection task, each
under focused attention. In the divided fixed training, participants practiced
combining verification and detection by divided attention, with equal attention
allocated to both tasks. In the divided variable training, participants completed
the task by divided attention, but were taught to vary the attentional priority
allocated to each task. Brain activation was measured with fMRI pre- and post
training while completing each task individually and the two tasks combined. The
three training programs resulted in markedly different brain changes. Practice on
individual tasks in the single repeated training resulted in reduced brain
activation whereas divided variable training resulted in a larger recruitment of
the right superior and middle frontal gyrus, a region that has been involved in
multitasking. The type of training is a critical factor in determining the
pattern of brain activation.
PMID- 25119465
TI - Functional balance between the hemagglutinin and neuraminidase of influenza
A(H1N1)pdm09 HA D222 variants.
AB - D222G/N substitutions in A(H1N1)pdm09 hemagglutinin may be associated with
increased binding of viruses causing low respiratory tract infections and human
pathogenesis. We assessed the impact of such substitutions on the balance between
hemagglutinin binding and neuraminidase cleavage, viral growth and in vivo
virulence.Seven viruses with differing polymorphisms at codon 222 (2 with D, 3 G,
1 N and 1 E) were isolated from patients and characterized with regards
hemagglutinin binding affinity (Kd) to alpha-2,6 sialic acid (SAalpha-2,6) and
SAalpha-2,3 and neuraminidase enzymatic properties (Km, Ki and Vmax). The
hemagglutination assay was used to quantitatively assess the balance between
hemagglutinin binding and neuraminidase cleavage. Viral growth properties were
compared in vitro in MDCK-SIAT1 cells and in vivo in BALB/c mice. Compared with
D222 variants, the binding affinity of G222 variants was greater for SAalpha-2,3
and lower for SAalpha-2,6, whereas that of both E222 and N222 variants was
greater for both SAalpha-2,3 and SAalpha-2,6. Mean neuraminidase activity of D222
variants (16.0 nmol/h/10(6)) was higher than that of G222 (1.7 nmol/h/10(6)
viruses) and E/N222 variants (4.4 nmol/h/10(6) viruses). The hemagglutination
assay demonstrated a deviation from functional balance by E222 and N222 variants
that displayed strong hemagglutinin binding but weak neuraminidase activity. This
deviation impaired viral growth in MDCK-SIAT1 cells but not infectivity in mice.
All strains but one exhibited low infectious dose in mice (MID50) and replicated
to high titers in the lung; this D222 strain exhibited a ten-fold higher MID50
and replicated to low titers. Hemagglutinin-neuraminidase balance status had a
greater impact on viral replication than hemagglutinin affinity strength, at
least in vitro, thus emphasizing the importance of an optimal balance for
influenza virus fitness. The mouse model is effective in assessing binding to
SAalpha-2,3 but cannot differentiate SAalpha-2,3- from SAalpha-2,6- preference,
nor estimate the hemagglutinin-neuraminidase balance in A(H1N1)pdm09 strains.
PMID- 25119468
TI - Combining XCO2 measurements derived from SCIAMACHY and GOSAT for potentially
generating global CO2 maps with high spatiotemporal resolution.
AB - Global warming induced by atmospheric CO2 has attracted increasing attention of
researchers all over the world. Although space-based technology provides the
ability to map atmospheric CO2 globally, the number of valid CO2 measurements is
generally limited for certain instruments owing to the presence of clouds, which
in turn constrain the studies of global CO2 sources and sinks. Thus, it is a
potentially promising work to combine the currently available CO2 measurements.
In this study, a strategy for fusing SCIAMACHY and GOSAT CO2 measurements is
proposed by fully considering the CO2 global bias, averaging kernel, and
spatiotemporal variations as well as the CO2 retrieval errors. Based on this
method, a global CO2 map with certain UTC time can also be generated by employing
the pattern of the CO2 daily cycle reflected by Carbon Tracker (CT) data. The
results reveal that relative to GOSAT, the global spatial coverage of the
combined CO2 map increased by 41.3% and 47.7% on a daily and monthly scale,
respectively, and even higher when compared with that relative to SCIAMACHY. The
findings in this paper prove the effectiveness of the combination method in
supporting the generation of global full-coverage XCO2 maps with higher temporal
and spatial sampling by jointly using these two space-based XCO2 datasets.
PMID- 25119469
TI - Targeting strategies for delivery of anti-HIV drugs.
AB - Human Immunodeficiency Virus (HIV) infection remains a significant cause of
mortality globally. Though antiretroviral therapy has significantly reduced AIDS
related morbidity and mortality, there are several drawbacks in the current
therapy, including toxicity, drug-drug interactions, development of drug
resistance, necessity for long-term drug therapy, poor bio-availability and lack
of access to tissues and reservoirs. To circumvent these problems, recent anti
HIV therapeutic research has focused on improving drug delivery systems through
drug delivery targeted specifically to host cells infected with HIV or could
potentially get infected with HIV. In this regard, several surface molecules of
both viral and host cell origin have been described in recent years, that would
enable targeted drug delivery in HIV infection. In the present review, we provide
a comprehensive overview of the need for novel drug delivery systems, and the
successes and challenges in the identification of novel viral and host-cell
molecules for the targeted drug delivery of anti-HIV drugs. Such targeted anti
retroviral drug delivery approaches could pave the way for effective treatment
and eradication of HIV from the body.
PMID- 25119466
TI - Anticancer activities of pterostilbene-isothiocyanate conjugate in breast cancer
cells: involvement of PPARgamma.
AB - Trans-3,5-dimethoxy-4'-hydroxystilbene (PTER), a natural dimethylated analog of
resveratrol, preferentially induces certain cancer cells to undergo apoptosis and
could thus have a role in cancer chemoprevention. Peroxisome proliferator
activated receptor gamma (PPARgamma), a member of the nuclear receptor
superfamily, is a ligand-dependent transcription factor whose activation results
in growth arrest and/or apoptosis in a variety of cancer cells. Here we
investigated the potential of PTER-isothiocyanate (ITC) conjugate, a novel class
of hybrid compound (PTER-ITC) synthesized by appending an ITC moiety to the PTER
backbone, to induce apoptotic cell death in hormone-dependent (MCF-7) and
independent (MDA-MB-231) breast cancer cell lines and to elucidate PPARgamma
involvement in PTER-ITC action. Our results showed that when pre-treated with
PPARgamma antagonists or PPARgamma siRNA, both breast cancer cell lines
suppressed PTER-ITC-induced apoptosis, as determined by annexin V/propidium
iodide staining and cleaved caspase-9 expression. Furthermore, PTER-ITC
significantly increased PPARgamma mRNA and protein levels in a dose-dependent
manner and modulated expression of PPARgamma-related genes in both breast cancer
cell lines. This increase in PPARgamma activity was prevented by a PPARgamma
specific inhibitor, in support of our hypothesis that PTER-ITC can act as a
PPARgamma activator. PTER-ITC-mediated upregulation of PPARgamma was counteracted
by co-incubation with p38 MAPK or JNK inhibitors, suggesting involvement of these
pathways in PTER-ITC action. Molecular docking analysis further suggested that
PTER-ITC interacted with 5 polar and 8 non-polar residues within the PPARgamma
ligand-binding pocket, which are reported to be critical for its activity.
Collectively, our observations suggest potential applications for PTER-ITC in
breast cancer prevention and treatment through modulation of the PPARgamma
activation pathway.
PMID- 25119470
TI - Single nucleotide polymorphisms other than factor V Leiden are associated with
coagulopathy and osteonecrosis of the femoral head in Chinese patients.
AB - Single nucleotide polymorphisms (SNPs) of factor V Leiden have been associated
with osteonecrosis of the femoral head (ONFH) in Caucasians but remains
controversial in Asians. We used an SNP microarray to screen 55 loci of factor V
gene in patients with ONFH of Chinese. Significantly different candidate SNPs at
14 loci were analyzed in 146 patients and 116 healthy controls using MALDI-TOF
(matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry
and gene sequencing. The factor V Leiden (rs6025) was not found in all
participants. Six SNP loci (rs9332595, rs6020, rs9332647, rs3766110, rs10919186,
and rs12040141) were confirmed with significant differences in patients but not
in controls. The rs6020 G-to-A polymorphism was found in 88.9% of the patients.
In addition, a high percentage (87.6%) of the patients had an abnormal
coagulation profile that included hyperfibrinogen, elevated fibrinogen
degradation products, elevated D-dimer, abnormal protein S, abnormal protein C,
or a decrease in anti-thrombin III. Patients with the rs6020 G-to-A polymorphism
(mutation) had a higher risk (odds ratio: 4.62; 95% confidence interval: 1.44
14.8) of having coagulation abnormalities than did those without the mutation
(wild-type) (chi(2) p = 0.006). Our findings suggested that the rs6020
polymorphism might be the genetic trait that accounts for the higher prevalence
of ONFH in the Chinese population than in Westerners. Exposure to risk factors
such as alcohol and steroids in patients with the rs6020 polymorphism causes
coagulation abnormalities and, subsequently, thromboembolisms in the femoral
head.
PMID- 25119471
TI - Longitudinal evaluation of the metabolic response of a tumor xenograft model to
single fraction radiation therapy using magnetic resonance spectroscopy.
AB - Proton magnetic resonance spectroscopy (MRS) was used to evaluate the metabolic
profile of human glioblastoma multiform brain tumors grown as xenografts in nude
mice before, and at multiple time points after single fraction radiation therapy.
Tumors were grown over the thigh in 16 mice in this study, of which 5 served as
untreated controls and 11 had their tumors treated to 800 cGy with 200 kVp x
rays. Spectra were acquired within 24 h pre-treatment, and then at 3, 7 and 14 d
post-treatment using a 9.4 T animal magnetic resonance (MR) system. For the
untreated control tumors, spectra (1-2 per mouse) were acquired at different
stages of tumor growth. Spectra were obtained with the PRESS pulse sequence using
a 3 * 3 * 3 mm(3) voxel. Analysis was performed with the LCModel software
platform. Six metabolites were profiled for this analysis: alanine (Ala), myo
inositol (Ins), taurine (Tau), creatine and phosphocreatine (Cr + PCr), glutamine
and glutamate (Glu + Gln), and total choline (glycerophosphocholine +
phosphocholine) (GPC + PCh). For the treated cohort, most metabolite/water
concentration ratios were found to decrease in the short term at 3 and 7 d post
treatment, followed by an increase at 14 d post-treatment toward pre-treatment
values. The lowest concentrations were observed at 7 d post-treatment, with
magnitudes (relative to pre-treatment concentration ratios) of: 0.42 +/- 24.6%
(Ala), 0.43 +/- 15.3% (Ins), 0.68 +/- 27.9% (Tau), 0.52 +/- 14.6%
(GPC+PCh), 0.49 +/- 21.0% (Cr + PCr) and 0.78 +/- 24.5% (Glu + Gln). Control
animals did not demonstrate any significant correlation between tumor volume and
metabolite concentration, indicating that the observed kinetics were the result
of the therapeutic intervention. We have demonstrated the feasibility of using
MRS to follow multiple metabolic markers over time for the purpose of evaluating
therapeutic response of tumors to radiation therapy. This study provides
supporting evidence that metabolite/water concentration ratios have the potential
to be used as biomarkers for the assessment of the response to therapy.
PMID- 25119472
TI - Prevalence of skin problems and leg ulceration in a sample of young injecting
drug users.
AB - BACKGROUND: Drug users suffer harm from the injecting process, and clinical
services are reporting increasing numbers presenting with skin-related problems
such as abscesses and leg ulcers. Skin breakdown can lead to long-term health
problems and increased service costs and is often the first indication of serious
systemic ill health. The extent of skin problems in injecting drug users has not
previously been quantified empirically, and there is a dearth of robust topical
literature. Where skin problems have been reported, this is often without clear
definition and generic terms such as 'soft tissue infection' are used which lack
specificity. The aim of this study was to identify the range and extent of skin
problems including leg ulceration in a sample of injecting drug users.
Definitions of skin problems were developed and applied to descriptions from drug
users to improve rigour. METHODS: Data were collected in needle exchanges and
methadone clinics across Glasgow, Scotland, from both current and former drug
injectors using face-to-face interviews. RESULTS: Two hundred participants were
recruited, of which 74% (n = 148) were males and 26% (n = 52) were females. The
age range was 21-44 years (mean 35 years). Just under two thirds (64%, n = 127)
were currently injecting or had injected within the last 6 months, and 36% (n =
73) had previously injected and had not injected for more than 6 months.Sixty per
cent (n = 120) of the sample had experienced a skin problem, and the majority
reported more than one problem. Most common were abscesses, lumps, track marks
and leg ulcers. Fifteen per cent (n = 30) of all participants reported having had
a leg ulcer. CONCLUSIONS: This is an original empirical study which demonstrated
unique findings of a high prevalence of skin disease (60%) and surprisingly high
rates of leg ulceration (15%). Skin disease in injecting drug users is clearly
widespread. Leg ulceration in particular is a chronic recurring condition that is
costly to treat and has long-term implications for drug users and services caring
for current or former injectors long after illicit drug use has ceased.
PMID- 25119473
TI - Unveiling viral-host interactions within the 'microbial dark matter'.
AB - Viruses control natural microbial communities. Identification of virus-host pairs
relies either on their cultivation or on metagenomics and tentative assignment
based on genomic signatures. Both approaches have severe drawbacks when aiming to
target such pairs within the uncultured majority. Here we present an unambiguous
way to assign viruses to hosts that does not rely on any previous information
about either of them nor requires their cultivation. First, genomic contents of
individual cells present in an environmental sample are retrieved by means of
single-cell genomic technologies. Then, individual cell genomes are hybridized
against a set of individual viral genomes from the same sample, previously
immobilized on a microarray. Infected cells will yield positive hybridization as
they carry viral genomes, which can be then sequenced and characterized. Using
this method, we pinpoint viruses infecting the ubiquitous hyperhalophilic
Nanohaloarchaeota, included in the so-called 'microbial dark matter' (the
uncultured fraction of the microbial world).
PMID- 25119475
TI - [The relevance of the trace elements zinc and iron in the milk fever disease of
cattle].
AB - OBJECTIVE: The aim of this study was to analyse the concentrations of Zn and Fe
as well as their relationships to metabolic parameters in milk fever cows.
MATERIAL AND METHODS: A total of 195 Simmental cows, downer cows and clinically
healthy control animals were divided into five groups: a) control group (CG, n =
21), b) all cows with milk fever (MF) (n = 174), c) MF cows without additional
diseases (n = 145), d) cows with MF and mastitis (n = 10) and e) cows with
retained placenta or endometritis (n = 19). Selenium (Se), zinc (Zn), iron (Fe),
calcium (Ca), inorganic phosphorus (Pi), tumour necrosis factor alpha (TNFalpha),
haptoglobin (Hp), antioxidants (Trolox Equivalent Antioxidative Capacity: TEAC),
non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), bilirubin, urea,
creatinine, glucose, cholesterol, gamma-glutamyl transferase (GGT) and alkaline
phosphatase (AP) were analysed in the blood serum. RESULTS: The concentrations of
Zn, Fe, Ca, Pi and TEAC were lower in groups b) to e) whereas Hp was higher than
in the CG (p <= 0.05). In group c), lower Ca and Pi concentrations were found
when compared to groups d) and e) (p <= 0.05). In group e), Zn concentrations
were significantly lower than in group c) (p <= 0.05). Zn was negatively
correlated with K (CG) and positively correlated with TEAC, Cu, Mn and Fe (groups
b and c) and with Mn (group e) (p <= 0.05). Fe was positively correlated with Ca
(group c), Pi (group c), K (groups b and c) and Mg (groups b-d) as well as with
Zn, Cu and Se (groups b and c) (p <= 0.05). In groups b) and c), TNFalpha was
increased and negatively correlated with Fe (p <= 0.05). AP activity in groups b)
and e) was lower than in the CG (p <= 0.05). CONCLUSION: These results and
literature data support the hypothesis that Zn and Fe could be engaged in bone
metabolism and be involved in the pathogenesis of MF. The concentrations of Hp
and TEAC support this interpretation. Control of the Zn and Fe status of cows and
Zn supplementation should be included in the prevention and advanced therapy of
MF.
PMID- 25119474
TI - Plasma B-type natriuretic peptide is a useful tool for assessing coronary heart
disease risk in a Japanese general population.
AB - B-type natriuretic peptide (BNP) has been reported to be associated with
cardiovascular prognosis in a community-based population. In addition,
accumulation of individual cardiovascular risk factors is important in predicting
an individual's risk of future cardiovascular disease. However, there have been
few reports showing that BNP is a comprehensive marker of the accumulation of
cardiovascular risk factors. We studied 1530 community-dwelling subjects without
obvious heart diseases or renal dysfunction (mean age 62 +/- 15 years; 569 men
and 961 women) who participated in an annual health checkup in a rural Japanese
community. Coronary heart disease (CHD) risk was estimated, and patients were
placed into the following three groups based on the Framingham function: low
risk, moderate risk and high risk. The prevalence of moderate- and high-risk
subjects for CHD rose in both genders with increasing plasma BNP levels. The area
under the receiver operating characteristic curve showed a modest ability of
plasma BNP levels to detect these subjects (0.755 and 0.700 for men and women,
respectively). The optimal thresholds for the identification of subjects with
moderate- and high-risk disease were BNP concentrations of 12.0 and 22.0 pg ml(
1), with sensitivities of 70% and 66% and specificities of 71% and 63% for men
and women, respectively. In conclusion, subjects with high plasma BNP levels were
at higher risk for CHD in a population without obvious heart disease or renal
dysfunction.
PMID- 25119476
TI - [Blood serum vitamin B12 concentration in dairy cows during early lactation].
AB - OBJECTIVE: To describe the characteristics of the blood serum vita- min B12
concentration of dairy cows post partum (p. p.) and to investigate its
relationship with metabolic parameters, the erythrogram and the health status of
the cows. MATERIAL AND METHODS: Blood samples from 157 Holstein-Friesian-cows
were obtained for metabolic analysis at 2-6 days p. p. and at 4-5 weeks p. p. In
addition, clinical findings were compiled to evaluate the health status
(healthy/morbid). RESULTS: In all animals a decline in the vitamin B12
concentration (p <= 0.05) at 4 weeks p. p. was observed. Animals of both groups
(healthy/morbid) had higher values for the erythrocyte count, haematocrit and
haemoglobin concentration 2-6 days p. p. when compared to 4 weeks p. p. In all
cows, gamma-glutamyl transferase (GGT) activity was closely correlated to the
vitamin B12 concentration (p <= 0.01). Furthermore, all animals displayed
elevated concentrations of beta-hydroxybutyrate, non-esterified fatty acids and
bilirubin (p <= 0.05) at 2-6 days p. p. as a consequence of partus-dependent
increased lipolysis. There was a smaller decrease in the vitamin B12
concentration in the morbid cows compared to the healthy cows (p <= 0.05).
CONCLUSIONS AND CLINICAL RELEVANCE: The vitamin B12 concentration is
significantly dynamic during lactation and displays a close relationship with the
GGT activity and the parameters of energy metabolism. Vitamin B12 may act as an
indicator for increased lipolysis and cholestasis. Higher vitamin B12
concentrations may indicate clinical problems. A relationship with haematopoiesis
is recognizable from the red cell readings. Decreasing red cell readings
associated with reduced performance could be related to a low vitamin B12
concentration. The close correlations of vitamin B12 with GGT activity and
bilirubin concentration may indicate cholestatic metabolic stress in dairy cows
at blood serum concentrations >= 227 ng/l (3rd quartile 2-6 days p. p. healthy
group). Morbid cows can already be identified at the subclinical stage.
PMID- 25119477
TI - [Energy intake and body weight development of Warmblood foals that changed stud
at weaning].
AB - OBJECTIVE: This study investigated the energy requirements of Warmblood foals
with a change of the stud at weaning. MATERIAL AND METHODS: Nine colts purchased
at weaning participated in the study aged approximately 6 months to 1 year. They
were transported to the stud by their breeders either having been separated from
their dams in their home stable or upon arrival at the stud. The foals were
offered a late first cut of haylage, oats and foal starter feed. To ensure
individual feeding of concentrates, the foals were tethered twice daily. The
total combined haylage intake of all foals per day was recorded. Individual
concentrate intake, body weight and body condition score (BCS) were documented at
4-week intervals. RESULTS: The total energy intake was 74 MJ digestible energy
(68 MJ metabolisable energy) per animal per day. The foals had been delivered at
the stud with a comparably low body weight (285 +/- 30 kg) and BCS (4.2 +/- 0.4
on a scale from 1 to 9). At the end of the study, aged 319 +/- 22 days, they
attained an average body weight of 326 +/- 24 kg and a BCS of 4.2 +/- 0.4. The
energy intake of the foals of this study was higher and their body weight
development slower than in foals of a parallel study, which were born and raised
in the stud and therefore exposed to less stressful weaning conditions.
CONCLUSION AND CLINICAL RELEVANCE: Foals with a comparatively low body weight and
BCS at weaning in combination with further stressors need considerably more
energy than foals that undergo less stressful weaning conditions.
PMID- 25119478
TI - [New drugs for horses and production animals in 2013].
AB - In 2013, only one newly developed active pharmaceutical ingredient for horses and
food-producing animals was released on the German market for veterinary drug
products. The ionophore monensin from the group of polyether antibiotics is now
available as an orally administered continuous release intraruminal device for
cattle (Kexxtone(r)). Furthermore, two established veterinary active
pharmaceutical ingredients are available for additional species: The antibiotic
amoxicillin (Suramox(r)) is also authorized for ducks and turkeys and the
dissociative anesthetic ketamine is now authorized for sheep, goats and dairy
cattle. Additionally, one veterinary drug with a new pharmaceutical form as well
as one product with a new strength have been launched on the market for
veterinary drugs for horses and food producing animals.
PMID- 25119479
TI - [Resection of a carpal bone row in a Pustertaler Sprinze cow with chronic
purulent arthritis of the carpal joint and osteomyelitis].
AB - This case report describes the clinical and radiographic findings and the
surgical treatment of a serofibrinous arthritis of the antebrachiocarpal joint
and of a chronic purulent arthritis of the intercarpal and carpometacarpal joints
with osteomyelitis of the distal carpal bones and subchondral osteomyelitis of
the proximal metacarpal bones in a cow of the breed "Pustertaler Sprinze". The
therapy comprised an arthrotomy of both joint spaces and the resection of the
distal row of the carpal bones. The right forelimb had been immobilised for 70
days by a full limb cast. After this period, radiographs revealed an ob- vious
ankylosis of the carpal joint, and the cow showed only a slight lameness. Six
years postoperatively this cow was still in the herd and had produced six calves.
PMID- 25119480
TI - [Tuberculosis in cattle - surprisingly re-emerging or continuously present?].
AB - Tuberculosis in cattle, caused by Mycobacterium (M.) bovis/M. caprae, is globally
one of the most important zoonotic diseases in cattle. It was widespread in
Germany until the second half of the 20th century. Due to the effective control
and eradication campaigns in Germany, the epidemic was almost eradicated.
Consequently, Germany was regarded as essentially tuberculosis free since the end
of 1961 (West) and the end of 1978 (East). By declaring the unified Germany
"officially free of tuberculosis" (OTF) in 1996, freedom from tuberculosis was
officially ratified by the European Commission. The prerequisite was the
detection of tuberculosis in less than 0.1% of the cattle holdings per year in
Germany. This status has been steadily maintained hitherto, thus resulting in
some loss of awareness of bovine tuberculosis by veterinarians, farmers and the
public over many decades. After 1996, the number of notified outbreaks had been
on average less than 10 per 200,000 cattle holdings per year for many years. It
was the year 2008 when the numbers increased. Based in part on subsequently
enhanced ante mortem testing efforts, 46 outbreaks were notified in 2013. Bavaria
and Lower Saxony were the federal states with the highest number of cases.
Consequently, the national tuberculosis regulation was revised in 2009, 2012 and
2013 to form the basis for a modification of tuberculosis surveillance.
Regionally, an improvement of the control strategy was considered necessary. In
addition to the traditionally applied examination and detection methods of the
tuberculin skin test (ante mortem) and bacteriological culture (post mortem), the
gamma-interferon-release assay (ante mortem) and the molecular detection of the
causative pathogen (post mortem) were introduced into the official collection of
recommended methods. Consequently, the diagnostic procedure of tuberculosis has
been accelerated. However, in many cases the increase in the range of available
test systems did not increase the ease in the interpretation of results.
PMID- 25119481
TI - Emerging issues in translating laboratory experiments to applications for
society.
PMID- 25119483
TI - Non invasive monitoring in mechanically ventilated pediatric patients.
AB - Cardiopulmonary monitoring is a key component in the evaluation and management of
critically ill patients. Clinicians typically rely on a combination of invasive
and non-invasive monitoring to assess cardiac output and adequacy of ventilation.
Recent technological advances have led to the introduction: of continuous non
invasive monitors that allow for data to be obtained at the bedside of critically
ill patients. These advances help to identify hemodynamic changes and allow for
interventions before complications occur. In this manuscript, we highlight
several important methods of non-invasive cardiopulmonary monitoring, including
capnography, transcutaneous monitoring, pulse oximetry, and near infrared
spectroscopy.
PMID- 25119482
TI - VirtualSpectrum, a tool for simulating peak list for multi-dimensional NMR
spectra.
AB - NMR spectroscopy is a widely used technique for characterizing the structure and
dynamics of macromolecules. Often large amounts of NMR data are required to
characterize the structure of proteins. To save valuable time and resources on
data acquisition, simulated data is useful in the developmental phase, for data
analysis, and for comparison with experimental data. However, existing tools for
this purpose can be difficult to use, are sometimes specialized for certain types
of molecules or spectra, or produce too idealized data. Here we present a fast,
flexible and robust tool, VirtualSpectrum, for generating peak lists for most
multi-dimensional NMR experiments for both liquid and solid state NMR. It is
possible to tune the quality of the generated peak lists to include sources of
artifacts from peak overlap, noise and missing signals. VirtualSpectrum uses an
analytic expression to represent the spectrum and derive the peak positions,
seamlessly handling overlap between signals. We demonstrate our tool by comparing
simulated and experimental spectra for different multi-dimensional NMR spectra
and analyzing systematically three cases where overlap between peaks is
particularly relevant; solid state NMR data, liquid state NMR homonuclear (1)H
and (15)N-edited spectra, and 2D/3D heteronuclear correlation spectra of
unstructured proteins. We analyze the impact of protein size and secondary
structure on peak overlap and on the accuracy of structure determination based on
data of different qualities simulated by VirtualSpectrum.
PMID- 25119484
TI - In vitro conversion of vinyl to formyl groups in naturally occurring
chlorophylls.
AB - The chemical structural differences distinguishing chlorophylls in oxygenic
photosynthetic organisms are either formyl substitution (chlorophyll b, d, and f)
or the degree of unsaturation (8-vinyl chlorophyll a and b) of a side chain of
the macrocycle compared with chlorophyll a. We conducted an investigation of the
conversion of vinyl to formyl groups among naturally occurring chlorophylls. We
demonstrated the in vitro oxidative cleavage of vinyl side groups to yield formyl
groups through the aid of a thiol-containing compound in aqueous reaction mixture
at room temperature. Heme is required as a catalyst in aqueous solution but is
not required in methanolic reaction mixture. The conversion of vinyl- to formyl-
groups is independent of their position on the macrocycle, as we observed
oxidative cleavages of both 3-vinyl and 8-vinyl side chains to yield formyl
groups. Three new chlorophyll derivatives were synthesised using 8-vinyl
chlorophyll a as substrate: 8-vinyl chlorophyll d, [8-formyl]-chlorophyll a, and
[3,8-diformyl]-chlorophyll a. The structural and spectral properties will provide
a signature that may aid in identification of the novel chlorophyll derivatives
in natural systems. The ease of conversion of vinyl- to formyl- in chlorophylls
demonstrated here has implications regarding the biosynthetic mechanism of
chlorophyll d in vivo.
PMID- 25119485
TI - Unique odd-chain polyenoic phospholipid fatty acids present in chytrid fungi.
AB - Chytrid fungi are ubiquitous components of aquatic and terrestrial ecosystems yet
they remain understudied. To investigate the use of phospholipid fatty acids as
phenotypic characteristics in taxonomic studies and biomarkers for ecological
studies, 18 chytrid fungi isolated from soil to freshwater samples were grown in
defined media and their phospholipid fatty acid profile determined. Gas
chromatographic/mass spectral analysis indicated the presence of fatty acids
typically associated with fungi, such as 16:1(n-7), 16:0, 18:2(n-6), 18:3(n-3)
18:1(n-9), and 18:0, as well as, a number of odd-chain length fatty acids,
including two polyunsaturated C-17 fatty acids. Conversion to their 3
pyridylcarbinol ester facilitated GC-MS determination of double-bond positions
and these fatty acid were identified as 6,9-17:2 [17:2(n-8)] and 6,9,12-17:3
[17:3(n-5)]. To the best of our knowledge, this is the first report of
polyunsaturated C-17 fatty acids isolated from the phospholipids of chytrid
fungi. Cluster analysis of PLFA profiles showed sufficient correlation with
chytrid phylogeny to warrant inclusion of lipid analysis in species descriptions
and the presence of several phospholipid fatty acids of restricted phylogenetic
distributions suggests their usefulness as biomarkers for ecological studies.
PMID- 25119487
TI - Expression of genes controlling unsaturated fatty acids biosynthesis and oil
deposition in developing seeds of Sacha inchi (Plukenetia volubilis L.).
AB - Sacha inchi (Plukenetia volubilis L., Euphorbiaceae) seed oil is rich in alpha
linolenic acid, a kind of n-3 fatty acids with many health benefits. To discover
the mechanism underlying alpha-linolenic acid accumulation in sacha inchi seeds,
preliminary research on sacha inchi seed development was carried out from one
week after fertilization until maturity, focusing on phenology, oil content, and
lipid profiles. The results suggested that the development of sacha inchi seeds
from pollination to mature seed could be divided into three periods. In addition,
investigations on the effect of temperature on sacha inchi seeds showed that
total oil content decreased in the cool season, while unsaturated fatty acid and
linolenic acid concentrations increased. In parallel, expression profiles of 17
unsaturated fatty acid related genes were characterized during seed development
and the relationships between gene expression and lipid/unsaturated fatty acid
accumulation were discussed.
PMID- 25119486
TI - Dietary lipid intake only partially influences variance in serum phospholipid
fatty acid composition in adolescents: impact of other dietary factors.
AB - The present study aimed to assess the correlation between food and fatty acid
(FA) intake and the serum phospholipid (PL) FA status in European adolescents and
explored the percentage of variation in serum PL FA that could be attributed to
dietary habits. Participants included 528 adolescents recruited in the HELENA
Study. Dietary intake was assessed by two, self-administered, non-consecutive 24
h recalls. PL FA concentrations were measured in fasting venous serum samples.
Reduced rank regressions were applied to examine the combined effect of food
intakes. Results indicated that the variance in serum PL FA in adolescents, that
could be explained by diet varied from 7.0% for MUFA to 14.2% for n-3FA. The
variance in the long-chain n-3FA was mainly explained by fish intake but also by
coffee and tea consumption. In conclusion this study indicated that dietary
intake influences the serum PL FA status to a limited amount but that also other
factors interfere. However, dietary intake is important as it is among those
factors that could be modified. Furthermore, the results suggest that the overall
dietary habits should be considered instead of only the consumption of single
foods or nutrients, as the medium of the food or concomitant intake of foods and
nutrients might interact and as such influence absorption or metabolism.
PMID- 25119488
TI - What are the factors that interplay from normal pregnancy to near miss maternal
morbidity in a Nigerian tertiary health care facility?
AB - Researchers in Nigeria examined the epidemiological characteristics and factors
associated with maternal outcomes using a mixed method approach: a prospective
case control study design involving 375 pregnant women who received maternal care
from a tertiary facility and in-depth interviews reporting the experience of near
miss survivors. A generalized ordered logit model was used to generate the
estimates of partial proportional odds ratios (and 95% confidence intervals)
across categories of the outcome variable. Factors strongly associated with
maternal morbidity were late referral of women, presence of complications at
booking antenatal visits, low birth weight, and severe birth asphyxia. The
nearmiss women were further characterized, and a low proportion (25%) had organ
dysfunction or failure. The challenge of such diagnoses in resource-constrained
settings raises questions about the appropriateness of using organ dysfunction
criteria in developing countries.
PMID- 25119491
TI - Ebola--underscoring the global disparities in health care resources.
PMID- 25119490
TI - Supporting cancer patients in illness management: usability evaluation of a
mobile app.
AB - BACKGROUND: Mobile phones and tablets currently represent a significant presence
in people's everyday lives. They enable access to different information and
services independent of current place and time. Such widespread connectivity
offers significant potential in different app areas including health care.
OBJECTIVE: Our goal was to evaluate the usability of the Connect Mobile app. The
mobile app enables mobile access to the Connect system, an online system that
supports cancer patients in managing health-related issues. Along with symptom
management, the system promotes better patient-provider communication,
collaboration, and shared decision making. The Connect Mobile app enables access
to the Connect system over both mobile phones and tablets. METHODS: The study
consisted of usability tests of a high fidelity prototype with 7 cancer patients
where the objectives were to identify existing design and functionality issues
and to provide patients with a real look-and-feel of the mobile system. In
addition, we conducted semistructured interviews to obtain participants' feedback
about app usefulness, identify the need for new system features and design
requirements, and measure the acceptance of the mobile app and its features
within everyday health management. RESULTS: The study revealed a total of 27
design issues (13 for mobile apps and 14 for tablet apps), which were mapped to
source events (ie, errors, requests for help, participants' concurrent feedback,
and moderator observation). We also applied usability heuristics to identify
violations of usability principles. The majority of violations were related to
enabling ease of input, screen readability, and glanceability (15 issues), as
well as supporting an appropriate match between systems and the real world (7
issues) and consistent mapping of system functions and interactions (4 issues).
Feedback from participants also showed the cancer patients' requirements for
support systems and how these needs are influenced by different context-related
factors, such as type of access terminal (eg, desktop computer, tablet, mobile
phone) and phases of illness. Based on the observed results, we proposed design
and functionality recommendations that can be used for the development of mobile
apps for cancer patients to support their health management process. CONCLUSIONS:
Understanding and addressing users' requirements is one of the main prerequisites
for developing useful and effective technology-based health interventions. The
results of this study outline different user requirements related to the design
of the mobile patient support app for cancer patients. The results will be used
in the iterative development of the Connect Mobile app and can also inform other
developers and researchers in development, integration, and evaluation of mobile
health apps and services that support cancer patients in managing their health
related issues.
PMID- 25119492
TI - Hiwi facilitates chemoresistance as a cancer stem cell marker in cervical cancer.
AB - Hiwi, also named PiwiL1, is a human homologue of the Piwi family which is
associated with stem cells and is overexpressed in several types of cancers. In
the present study, we aimed to investigate the role of Hiwi in cervical
carcinogenesis. Immunochemical analysis showed a significantly higher frequency
of Hiwi staining in high-grade squamous intraepithelial lesions (HSILs) and
cervical cancer tissues when comparing with the frequency in normal cervices.
Particularly, Hiwi staining was restricted to basal cells of the normal cervix
and was associated with the progression of cervical cancer and chemotherapy
resistance. We further found that ectopic Hiwi increased the chemical resistance
in SiHa cells, and silencing of Hiwi in HeLa cells decreased the cell viability.
In addition, as a cancer stem cell marker, Hiwi promoted the tumorsphere
formation in vitro and tumorigenicity in vivo and elevated the expression of
several stem cell self-renewal-associated transcription factors, in spite of
inhibited the proliferation. These results suggest that Hiwi may participate in
the carcinogenesis of cervical cancer and may be a potential therapeutic target
molecule for cervical cancers.
PMID- 25119493
TI - Bisphenol A modulates colorectal cancer protein profile and promotes the
metastasis via induction of epithelial to mesenchymal transitions.
AB - More and more evidences indicate that endocrine disruptor chemicals such as
bisphenol A (BPA) can act as carcinogens and enhance susceptibility to
tumorigenesis. Although the gut is in direct contact with orally ingested BPA,
effects of BPA on occurrence and development of colorectal cancer remain an
unexplored endpoint. Colorectal cancer SW480 cells treated with nanomolar (10(-8)
M) or greater (10(-5) M) concentrations of BPA were compared with responses of a
control group. Proteomic study revealed that more than 56 proteins were modulated
following exposure to BPA, which are relevant to structure, motility and
proliferation of cells, production of ATP, oxidative stress, and protein
metabolism. Further studies revealed that BPA increased migration and invasion
and triggered transformations from epithelial to mesenchymal transitions (EMTs)
of colorectal cancer cells, which was characterized by acquiring mesenchymal
spindle-like morphology and increasing the expression of N-cadherin with a
concomitant decrease of E-cadherin. Accordingly, BPA treatment increased the
expression of transcription factor Snail. Furthermore, signal AKT/GSK-3beta
mediated stabilization of Snail is involved during BPA-induced EMT of colon
cancer cells. Our study first demonstrated that the xenoestrogen BPA at nanomolar
and greater concentrations modulates the protein profiles and promotes the
metastasis of colorectal cancer cells via induction of EMT.
PMID- 25119495
TI - Doctor-patient/family relationships: current status and projections for the
future.
PMID- 25119494
TI - Biology of ferritin in mammals: an update on iron storage, oxidative damage and
neurodegeneration.
AB - Iron is an abundant transition metal that is essential for life, being associated
with many enzyme and oxygen carrier proteins involved in a variety of fundamental
cellular processes. At the same time, the metal is potentially toxic due to its
capacity to engage in the catalytic production of noxious reactive oxygen
species. The control of iron availability in the cells is largely dependent on
ferritins, ubiquitous proteins with storage and detoxification capacity. In
mammals, cytosolic ferritins are composed of two types of subunits, the H and the
L chain, assembled to form a 24-mer spherical cage. Ferritin is present also in
mitochondria, in the form of a complex with 24 identical chains. Even though the
proteins have been known for a long time, their study is a very active and
interesting field yet. In this review, we will focus our attention to mammalian
cytosolic and mitochondrial ferritins, describing the most recent advancement
regarding their storage and antioxidant function, the effects of their genetic
mutations in human pathology, and also the possible involvement in non-iron
related activities. We will also discuss recent evidence connecting ferritins and
the toxicity of iron in a set of neurodegenerative disorder characterized by
focal cerebral siderosis.
PMID- 25119496
TI - Peer victimization, caregiver restriction of food intake, and degree of
overweight in youth.
AB - OBJECTIVE: Although caregiver restriction of child food intake is a common weight
control strategy, factors that make a caregiver more likely to engage in
restriction have not been fully explored. This study examined the relations
between child weight, peer victimization, and restriction. Peer victimization was
expected to serve as a mechanism through which child weight was associated with
restriction. METHOD: Two hundred fourteen youth (6-17 yr) were recruited from
pediatric primary care clinics in the South. Youth reported their levels of peer
victimization, and caregivers reported on their use of restriction of child food
intake. Child height and weight were obtained from medical records. RESULTS:
Ethnic minority adolescent females were more likely to be obese than nonethnic
minority adolescents/children. Greater child body mass index (BMI)-z was
associated with increased caregiver restriction (B = 0.86, p < .05) and peer
victimization (B = 0.66, p < .05). When peer victimization was entered into the
model of BMI-z predicting caregiver restriction of child food intake, the
relationship between these 2 variables decreased from 74% to 46% and was no
longer significant (B = 0.68, p = .08). However, the test of the indirect effect
was not significant. CONCLUSIONS: Greater degree of overweight was associated
with increased peer victimization, which in turn related to caregiver restriction
of food intake. Children's social relationships may serve as an impetus for
caregivers to engage in child weight control practices. Clinicians should
regularly screen for weight-related peer difficulties and provide caregivers with
guidance on healthy versus unhealthy weight control practices to promote overall
child health.
PMID- 25119489
TI - The recombinant expression systems for structure determination of eukaryotic
membrane proteins.
AB - Eukaryotic membrane proteins, many of which are key players in various biological
processes, constitute more than half of the drug targets and represent important
candidates for structural studies. In contrast to their physiological
significance, only very limited number of eukaryotic membrane protein structures
have been obtained due to the technical challenges in the generation of
recombinant proteins. In this review, we examine the major recombinant expression
systems for eukaryotic membrane proteins and compare their relative advantages
and disadvantages. We also attempted to summarize the recent technical strategies
in the advancement of eukaryotic membrane protein purification and
crystallization.
PMID- 25119497
TI - On the nature of non-covalent interactions in isomers of 2,5-dichloro-1,4
benzoquinone dimers - ground- and excited-state properties.
AB - The competition between non-covalent interactions (NCIs), such as C-H???O, C
H???Cl, C-Cl???O, C-Cl???Cl-C, C-O???C, C-Cl???C and C-O???pi, in the isomers of
the 2,5-dichloro-1,4-benzoquinone (DCBQ) dimer were investigated by quantum
chemical calculations to study the properties of the ground and excited states.
All the interactions were identified through bond critical points (BCP) with an
atoms in molecule (AIM) study. Isomer 1 (IH) and isomer 6 (IP) were surprisingly
very stable, and the largest stabilization energies of 4.16 and 5.39 kcal mol(
1), respectively, were observed for the ground state and 5.67 and 6.07 kcal mol(
1), respectively, were observed for the excited state at the MP2/6-31++G(d,p)
level of theory. The orientations of the excited-state isomers were similar to
those of the ground-state except for isomer 5 (IX) and isomer 9 (IM), which
disturbed the relative energy stability order. The calculated absorption spectra
have shown two absorption splits for isomers 5, 7, 8 and 9 through the acute
angle between the transition dipole moment of the monomers. The circular
dichroism (CD) couplet of the CD spectrum and the value of optical rotation (OR)
have indicated that isomers 1, 3, 5, 7, 8 and 9 have chiral characteristics. The
study of the absorption and CD spectra has revealed the impact of intermolecular
NCIs on chirality.
PMID- 25119498
TI - MacroH2A suppresses the proliferation of the B16 melanoma cell line.
AB - MacroH2A is the most frequently altered histone, which participates in cancer
progression. Increasing evidence demonstrates that cancer progression could be
regulated by macroH2A by affecting the cell cycle. In the present study, it was
demonstrated that macroH2A suppresses melanoma cell progression and the molecular
mechanisms underlying this process were examined. The interference and
overexpression vectors of macroH2A were constructed and then transferred into B16
melanoma cells and, following transfection, were analyzed by quantitative
polymerase chain reaction (PCR), western blot analysis and immunofluorescence
assays. Apoptosis and the cell cycle stage among all the treatment groups were
detected. Then, cyclin D1, cyclin D3, cyclin-dependent protein kinase (CDK) 4,
CDK6 and CDK8 expression was detected in order to elucidate the effects of
macroH2A on cell cycle-related genes. The results demonstrated that the
overexpression of macroH2A suppressed melanoma cell progression and arrested the
cells in the G2/M stage. Furthermore, macroH2A inhibits cyclin D1, cyclin D2,
CDK6 and CDK8 expression in B16 melanoma cells. In conclusion, the results
demonstrated that macroH2A, a critical component of chromatin, suppresses the
development of melanoma (which results from a disordered cell cycle) through
regulating cyclin D1, cyclin D3 and CDK6 genes.
PMID- 25119499
TI - Use of linked electronic health records to assess mortality and length of stay
associated with pandemic influenza A(H1N1)pdm09 at a UK teaching hospital.
AB - Effective use of data linkage is becoming an increasingly important focus in the
new healthcare system in England. We linked data from the results of a multiplex
PCR assay for respiratory viruses for a population of 230 inpatients at a UK
teaching hospital with their patient administrative system records in order to
compare the mortality and length of stay of patients who tested positive for
influenza A(H1N1)pdm09 with those positive for another influenza A virus. The
results indicated a reduced risk of death among influenza A(H1N1)pdm09 patients
compared to other influenza A strains, with an adjusted risk ratio of 0.25 (95%
confidence interval 0.08-0.75, P = 0.01), while no significant differences were
found between the lengths of stay in the hospital for these two groups. Further
development of such methods to link hospital data in a routine fashion could
provide a rapid means of gaining epidemiological insights into emerging
infectious diseases.
PMID- 25119500
TI - Development and cross-validation of prognostic models to assess the treatment
effect of cisplatin/pemetrexed chemotherapy in lung adenocarcinoma patients.
AB - Better understanding of the treatment effect of cisplatin/pemetrexed chemotherapy
on lung adenocarcinoma patients is needed to facilitate chemotherapy planning and
patient care. In this retrospective study, we will develop prognostic models by
the cross-validation method using clinical and serum factors to predict outcomes
of cisplatin/pemetrexed chemotherapy in lung adenocarcinoma patients. Lung
adenocarcinoma patients admitted between 2008 and 2013 were enrolled. 29 serum
parameters of laboratory tests and 14 clinical factors were analyzed to develop
the prognostic models. First, the stepwise selection and five-fold cross
validation were performed to identify candidate prognostic factors. Then a
classification of all patients based on the number of metastatic sites resulted
in four distinct subsets. In each subset, a prognostic model was fitted with the
most accurate prognostic factors from the candidate prognostic factors.
Categorical survival prediction was estimated using a log-rank test and
visualized with Kaplan-Meier method. 227 lung adenocarcinoma patients were
enrolled. Twenty candidate prognostic factors evaluated using the five-fold cross
validation method were total protein, total bilirubin, direct bilirubin, creatine
kinase, age, smoking index, neuron-specific enolase, bone metastasis, total
triglyceride, albumin, gender, uric acid, CYFRA21-1, lymph node metastasis, liver
metastasis, lactate dehydrogenase, CA153, peritoneal metastasis, CA125, and
CA199. From these 20 candidate prognostic factors, the multivariate Cox
proportional hazard model with the highest prognostic accuracy in each subset was
identified by the stepwise forward selection method, which generated significant
prognostic stratifications in Kaplan-Meier survival analyses (all log-rank p <
0.01). Generally, the prognostic models using five-fold cross-validation achieve
a good prediction performance. The prognostic models can be administered safely
to lung adenocarcinoma patients treated with first-line cisplatin/pemetrexed
chemotherapy, and a comprehensive assessment of clinical and serum factors helps
predict the outcomes of cisplatin/pemetrexed chemotherapy.
PMID- 25119501
TI - Evaluation of docetaxel- and oxaliplatin-based adjuvant chemotherapy in
postgastrectomy gastric cancer patients reveals obvious survival benefits in
docetaxel-treated mixed signet ring cell carcinoma patients.
AB - The purpose of this study was to determine the disease-free and overall survival
(DFS and OS, respectively) in 991 postgastrectomy gastric cancer patients
untreated (n = 372) or treated with either oxaliplatin-based (n = 376) or
docetaxel-based (n = 243) chemotherapy and to identify prognostic factors that
could help establish subgroups of patients who would benefit from such treatment.
The median follow-up duration was 55.3 months (range 31.2-90.8 months). Subgroup
analyses revealed that gastric adenocarcinoma (DFS 56.9 vs 53.2 months, P =
0.180, chi(2) = 1.802; OS not reached vs 70.7 months, P = 0.521, chi(2) = 0.412),
but not absolute signet ring cell (SRC) carcinoma (DFS 15.1/18.0 vs 10.1 months,
P = 0.171/0.259, chi(2) = 1.874/1.275; OS 21.0/26.1 vs 20.5 months, P =
0.551/0.196, chi(2) = 0.355/1.674), patients undergoing either docetaxel- or
oxaliplatin-based chemotherapy had a lower risk of recurrence and increased
survival in comparison to those without chemotherapy. In the mixed SRC carcinoma
patients, DFS and OS of patients treated with docetaxel-based regimen had a
longer survival (DFS 50.1 vs 29.9 months, P = 0.046, chi(2) = 3.987; OS not
reached vs 48.6 months, P = 0.016, chi(2) = 5.854) and lower risk of recurrence
and death (DFS HR 0.540, 95 % CI 0.355-0.874, P = 0.012; OS HR 0.452, 95 % CI
0.259-0.790, P = 0.005) than oxaliplatin-based chemotherapy. Cumulatively, our
results indicate that adjuvant chemotherapy is beneficial and that docetaxel
based regimen should be considered for patients with mixed SRC carcinoma.
PMID- 25119502
TI - EBP50 inhibits the migration and invasion of human breast cancer cells via
LIMK/cofilin and the PI3K/Akt/mTOR/MMP signaling pathway.
AB - The scaffold protein ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50, also
known as NHERF1 or NHERF) inhibits epidermal growth factor (EGF)-induced breast
cancer cell proliferation after 3 days by blocking EGF receptor (EGFR)
phosphorylation. The loss of EBP50 stimulates EGFR activity and induces the
appearance of epithelial-to-mesenchymal transition phenotypic features in biliary
cancer cells. However, the involvement of EBP50 in breast cancer migration and
invasion remains unknown. We report that EBP50 inhibits the migration and
invasion of breast cancer cells by inhibiting the phosphorylation of LIN-11,
Isl1, and MEC-3 protein domain kinase, as well as cofilin. This phosphorylation
is a critical step in cofilin recycling and actin polymerization mediating
cytoskeletal rearrangement. Additionally, EGF-induced phosphorylation of Akt and
mTOR was suppressed by upregulation of EBP50. Our results indicate that EBP50 is
significantly involved in breast cancer invasion/metastasis via LIMK/cofilin and
the PI3K/Akt/mTOR/MMP signaling pathway.
PMID- 25119503
TI - Toxicity of concurrent chemoradiotherapy with cetuximab for locoregionally
advanced nasopharyngeal carcinoma.
AB - Overexpression of the epidermal growth factor receptor can be found in 80 % of
patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and is
associated with shorter survival. In this work, we evaluated the feasibility of
adding cetuximab to concurrent cisplatin and radiotherapy (RT) in locoregionally
advanced NPC. Twenty-eight patients with locoregionally advanced NPC who received
the combination therapy were retrospectively reviewed and short-term efficacy was
evaluated. Grade 3-4 oral mucositis occurred in 20 (71.4 %) patients. Grade 3
radiotherapy-related dermatitis occurred in seven patients (25 %). Three patients
(14.3 %) had grade 3 and one patient (3.6 %) had grade 4 cetuximab-related
acneiform rashes. These grade 3-4 skin and mucosal toxic effects were manageable
and reversible. At a median follow-up of 33.4 months (95 % CI 29.2-38.1 months),
the 2-year progression-free survival was 89.3 % (95 % CI 76.4-98.1 %). In
conclusion, concurrent administration of cetuximab, cisplatin and RT is a
feasible strategy against locoregionally advanced NPC. Preliminary survival data
compare favorably with historic data and further follow-up is warranted.
PMID- 25119504
TI - Co-expression of EGFR and CK5/6 in primary squamous cell carcinoma of the breast.
AB - Primary squamous cell carcinoma of the breast (PSCCB) is an extremely rare breast
tumor lacking hormone receptors and HER2 expression. However, in comparison with
triple-negative invasive ductal carcinoma (TN-IDC), little is known about the
PSCCB. Twenty-nine patients with PSCCB in Sun Yat-sen University Cancer Center
from 1995 to 2010 were recruited in this study, along with 681 cases of TN-IDC
during the same period. The clinicopathologic features and prognosis of PSCCB
compared to TN-IDC were assessed. Furthermore, biomarkers of EGFR, CK5/6, E
cadherin, VEGF, TOPII, and p53 were immunostained to investigate the prognostic
determinant of PSCCB. Patients with PSCCB were older than those with TN-IDC (P =
0.009) and presented with lower lymph node involvement (P = 0.015). There was no
difference in overall survival (OS) between PSCCB and TN-IDC. However, the
disease-free survival (DFS) of PSCCB was poorer than that of TN-IDC (P = 0.007).
Multivariate analysis revealed that combined over-expression of EGFR and CK5/6
was the only independent prognostic factor for OS of PSCCB (HR 6.08, 95 % CI 1.33
27.85, P = 0.020) and associated with lymphatic metastasis (P = 0.023) and p53
expression (P = 0.013). Other predictors for poorer OS and DFS were lymphatic
metastasis and stage III, which failed to show significance after multivariate
analysis. Furthermore, platinum-based chemotherapy was identified to improve the
OS of PSCCB with EGFR + CK5/6+ (P = 0.027). The prognosis of PSCCB is poorer than
that of TN-IDC. As the only independent prognostic factor for PSCCB, combined
over-expression of EGFR and CK5/6 might be a potential indicator for the use of
platinum-based chemotherapy.
PMID- 25119505
TI - Biomimetic Randall's plaque as an in vitro model system for studying the role of
acidic biopolymers in idiopathic stone formation.
AB - Randall's plaque (RP) deposits seem to be consistent among the most common type
of kidney stone formers, idiopathic calcium oxalate stone formers. This group
forms calcium oxalate renal stones without any systemic symptoms, which
contributes to the difficulty of understanding and treating this painful and
recurring disease. Thus, the development of an in vitro model system to study
idiopathic nephrolithiasis, beginning with RP pathogenesis, can help in
identifying how plaques and subsequently stones form. One main theory of RP
formation is that calcium phosphate deposits initially form in the basement
membrane of the thin loops of Henle, which then fuse and spread into the
interstitial tissue, and ultimately make their way across the urothelium, where
upon exposure to the urine, the mineralized tissue serves as a nidus for
overgrowth with calcium oxalate into a stone. Our group has found that many of
the unusual morphologies found in RP and stones, such as concentrically laminated
spherulites and mineralized collagenous tissue, can be reproduced in vitro using
a polymer-induced liquid precursor (PILP) process, in which acidic polypeptides
induce a liquid phase amorphous precursor to the mineral, yielding non
equilibrium crystal morphologies. Given that there are many acidic proteins and
polysaccharides present in the renal tissue and urine, we have put forth the
hypothesis that the PILP system may be involved in urolithiasis. Therefore, our
goal is to develop an in vitro model system of these two stages of composite
stone formation to study the role that various acidic macromolecules may play. In
our initial experiments presented here, the development of "biomimetic" RP was
investigated, which will then serve as a nidus for calcium oxalate overgrowth
studies. To mimic the tissue environment, MatriStem((r)) (ACell, Inc.), a
decellularized porcine urinary bladder matrix was used, because it has both an
intact epithelial basement membrane surface and a tunica propria layer, thus
providing the two types of matrix constituents found associated with mineral in
the early stages of RP formation. We found that when using the PILP process to
mineralize this tissue matrix, the two sides led to dramatically different
mineral textures, and they bore a striking resemblance to native RP, which was
not seen in the tissue mineralized via the classical crystal nucleation and
growth process. The interstitium side predominantly consisted of collagen
associated mineral, while the luminal side had much less mineral, which appeared
to be tiny spherules embedded within the basement membrane. Although these
studies are only preliminary, they support our hypothesis that kidney stones may
involve non-classical crystallization pathways induced by the large variety of
macromolecular species in the urinary environment. We believe that mineralization
of native tissue scaffolds is useful for developing a model system of stone
formation, with the ultimate goal of developing strategies to avoid RP and its
detrimental consequences in stone formation, or developing therapeutic treatments
to prevent or cure the disease. Supported by NIDDK grant RO1DK092311.
PMID- 25119508
TI - Nitroxide-labeled pyrimidines for non-covalent spin-labeling of abasic sites in
DNA and RNA duplexes.
AB - Non-covalent and site-directed spin labeling gives easy access to spin-labeled
nucleic acids for the study of their structure and dynamics by electron
paramagnetic resonance (EPR) spectroscopy. In a search for improved spin labels
for non-covalent binding to abasic sites in duplex DNA and RNA, ten pyrimidine
derived spin labels were prepared in good yields and their binding was evaluated
by continuous wave (CW)-EPR spectroscopy. Most of the spin labels showed lower
binding affinity than the previously reported label c towards abasic sites in DNA
and RNA. The most promising labels were triazole-linked spin labels and a
pyrrolocytosine label. In particular, the N1-ethylamino derivative of a triazole
linked uracil spin label binds fully to both DNA and RNA containing an abasic
site. This is the first example of a spin label that binds fully through non
covalent interactions with an abasic site in RNA.
PMID- 25119507
TI - R2CHADS2 score is significantly associated with ankle-brachial index <0.9 in
patients without atrial fibrillation.
AB - OBJECTIVE: Previous studies demonstrated CHADS2 score and impaired renal function
were both associated with ankle-brachial index (ABI) < 0.9 in patients without
atrial fibrillation (AF). Hence, we hypothesized the R2CHADS2 score had a
significant correlation with ABI < 0.9 and the aim of this study was to validate
this association in non-AF patients. METHODS: A total of 1482 patients without AF
were included. ABI was measured using an ABI-form device. Peripheral arterial
occlusive disease (PAOD) was defined as ABI < 0.9 in either leg. RESULTS: Of the
1482 subjects, the prevalence of ABI < 0.9 was 5.6%. Multivariate analysis showed
that increased age (odds ratio [OR], 1.049; P < 0.001), decreased estimated
glomerular filtration rate (OR, 0.978; P = 0.006), and increased R2CHADS2 score
(OR, 1.738; P < 0.001) were associated with ABI < 0.9. In addition, in patients
with CHADS2 score ? 2, the presence of chronic kidney disease (CKD) was
significantly associated with ABI < 0.9 (P ? 0.006), but in patients with CHADS2
score < 2, there was no such association (P = 0.357). CONCLUSIONS: Our study
demonstrated R2CHADS2 score was positively correlated with ABI < 0.9. In
addition, the presence of CKD was a risk factor of ABI < 0.9 in patients with
CHADS2 score ? 2. Hence, increased R2CHADS2 score in non-AF patients and the
presence of CKD in non-AF patients with CHADS2 score ? 2 were useful parameters
in identifying the high risk group of PAOD.
PMID- 25119509
TI - Improving the Multidisciplinary Treatment of Chronic Pain by Stimulating Body
Awareness: A Cluster-randomized Trial.
AB - BACKGROUND: Because of methodological flaws and a lack of theoretical foundation
of body awareness (BA) in previous effect studies of interventions directed to
stimulate BA, it is impossible to attribute treatment effects to this specific
component of a multidisciplinary treatment. Therefore, this study evaluated short
term and long-term effects of a multidisciplinary pain rehabilitation program
with and without psychomotor therapy (PMT), which focused on BA (measured by the
scale of body connection) as a primary target of intervention. METHODS: Ninety
four patients clustered in 20 treatment groups were cluster randomized, using a
biased-coin design, to multidisciplinary treatment as usual with or without PMT.
Outcome variables were health-related quality of life, disability, and
depression. BA, catastrophizing, and self-efficacy were measured as potential
process variables. Assessments were performed at baseline, directly after
treatment, and at 3, 6, and 12 month follow-ups. The data were analyzed by linear
mixed-model analysis according to the intention-to-treat principle. RESULTS: Data
of all 94 patients were used for analyses. After treatment, significant
differences favoring PMT were found between conditions on depression (regression
coefficient [RC]=-5.01; 95% confidence interval [CI], -8.81 to -1.21), BA
(RC=0.23; 95% CI, 0.04 to 0.42) and catastrophizing (RC=-4.76; 95% CI, -8.03 to
1.48). These differences were no longer significant for depression at the 3-month
follow-up and for catastrophizing at the 6-month follow-up. CONCLUSIONS: No
clinical meaningful differences were found between treatment conditions in the
primary outcome measures health-related quality of life and disability. However,
this is the first long-term RCT that has shown that PMT improves BA in patients
with chronic pain and shows good effect size and a significant decrease for
catastrophizing.
PMID- 25119506
TI - Unified theory on the pathogenesis of Randall's plaques and plugs.
AB - Kidney stones develop attached to sub-epithelial plaques of calcium phosphate
(CaP) crystals (termed Randall's plaque) and/or form as a result of occlusion of
the openings of the Ducts of Bellini by stone-forming crystals (Randall's plugs).
These plaques and plugs eventually extrude into the urinary space, acting as a
nidus for crystal overgrowth and stone formation. To better understand these
regulatory mechanisms and the pathophysiology of idiopathic calcium stone
disease, this review provides in-depth descriptions of the morphology and
potential origins of these plaques and plugs, summarizes existing animal models
of renal papillary interstitial deposits, and describes factors that are believed
to regulate plaque formation and calcium overgrowth. Based on evidence provided
within this review and from the vascular calcification literature, we propose a
"unified" theory of plaque formation-one similar to pathological
biomineralization observed elsewhere in the body. Abnormal urinary conditions
(hypercalciuria, hyperoxaluria, and hypocitraturia), renal stress or trauma, and
perhaps even the normal aging process lead to transformation of renal epithelial
cells into an osteoblastic phenotype. With this de-differentiation comes an
increased production of bone-specific proteins (i.e., osteopontin), a reduction
in crystallization inhibitors (such as fetuin and matrix Gla protein), and
creation of matrix vesicles, which support nucleation of CaP crystals. These
small deposits promote aggregation and calcification of surrounding collagen.
Mineralization continues by calcification of membranous cellular degradation
products and other fibers until the plaque reaches the papillary epithelium.
Through the activity of matrix metalloproteinases or perhaps by brute physical
force produced by the large sub-epithelial crystalline mass, the surface is
breached and further stone growth occurs by organic matrix-associated nucleation
of CaOx or by the transformation of the outer layer of CaP crystals into CaOx
crystals. Should this theory hold true, developing an understanding of the
cellular mechanisms involved in progression of a small, basic interstitial plaque
to that of an expanding, penetrating plaque could assist in the development of
new therapies for stone prevention.
PMID- 25119510
TI - Experimental Pelvic Pain Impairs the Performance During the Active Straight Leg
Raise Test and Causes Excessive Muscle Stabilization.
AB - OBJECTIVES: The active straight leg raise (ASLR) test is widely used clinically
to assess severity of lumbopelvic pain due to decreased stability of the
sacroiliac joint (SIJ). This study aimed to bypass the influence of decreased SIJ
stability on the ASLR test by investigating the effect of experimental pelvic
pain and hyperalgesia on the outcome of the ASLR test. METHODS: Thirty-four
healthy participants took part in this randomized crossover study. Pelvic pain
was induced by injecting hypertonic saline into the long posterior sacroiliac
ligament. Isotonic saline was injected on the contralateral side as control. Pain
intensity was assessed on an electronic visual analogue scale. The Likert scores
of difficulty performing the ASLR test and simultaneous electromyography of trunk
and thigh muscles were recorded before, during, and postpain. Pressure pain
thresholds were assessed bilaterally in the pelvic area and lower limb. RESULTS:
Compared with the control condition and baseline, hypertonic saline injections
caused (P<0.05): (1) higher visual analogue scale scores of the pain intensity;
(2) reduced pressure pain thresholds at the injection site and lateral to S2; (3)
increased difficulty in performing the ASLR rated on the Likert scale; and (4)
bilateral increase in the electromyography activity of stabilizing trunk and
thigh muscles during pain. DISCUSSION: These data demonstrate that pain and
hyperalgesia in conditions unaffected by biomechanical SIJ impairments change the
outcome of the ASLR test toward what is seen in clinical lumbopelvic pain. This
may implicate pain-related changes in motor control strategies potentially
relevant for the transition from acute into chronic pain.
PMID- 25119512
TI - Effect of spinal cord stimulation on sensory characteristics: a randomized,
blinded crossover study.
AB - OBJECTIVES: Spinal cord stimulation (SCS) is increasingly used to treat various
chronic pain conditions. One undetermined issue is to what extent SCS alters the
processing of sensory information from the periphery, including those stimuli
that are mediated by small-fiber populations. We aimed to investigate these
possible changes using quantitative sensory testing (QST). METHODS: Fourteen
patients in long-term SCS treatment for complex regional pain syndrome (n=5) or
pain following peripheral nerve injury (n=9) were examined with QST. All patients
answered questions about their pain and underwent QST while the SCS treatment was
activated and deactivated (12 h interval between the sessions) in a randomized,
double-blinded crossover setting. Both the painful side and the corresponding
contralateral side were examined. RESULTS: Thermal and mechanical thresholds were
similar during SCS activation and deactivation. The same result was found for
intensity of pain and areas with painful symptoms even though all patients had
documented long-term benefit of the treatment. DISCUSSION: The results support
existing evidence suggesting that SCS does not change sensory characteristics,
which is important information for both patients and clinicians. Changes in pain
intensity after deactivation of SCS may be different in short-term and long-term
SCS treatment.
PMID- 25119511
TI - Onset of analgesia and efficacy of ibuprofen sodium in postsurgical dental pain:
a randomized, placebo-controlled study versus standard ibuprofen.
AB - OBJECTIVES: A novel, immediate-release tablet formulation of ibuprofen (IBU)
sodium dihydrate, Advil Film Coated Tablets (IBUNa), has been developed that is
absorbed faster than standard IBU tablets. The objective of the current study was
to compare the efficacy and onset of analgesia of this new formulation with
standard IBU tablets after a single dose. MATERIALS AND METHODS: Patients (N=316)
with at least moderate baseline postsurgical dental pain were randomized to 400
mg IBUNa, Advil (IBUAdv), Motrin (IBUMot), or placebo. Primary endpoints were
time-weighted sum of pain relief (PR) and pain intensity differences over 8 hours
(SPRID 0-8) and time to onset of meaningful pain relief (TMPR) measured by the
double-stopwatch method. RESULTS: SPRID 0-8 was significantly greater for IBUNa
and the other active treatments versus placebo (P<0.001). IBUNa had a
significantly earlier TMPR versus placebo, pooled IBUAdv/IBUMot, and IBUMot
(P<0.001 for all), and a marginally faster TMPR (P=0.075) versus IBUAdv. Results
for secondary endpoints were similar. Adverse events were comparable across
treatment groups, with gastrointestinal disorders being most frequently reported.
Most adverse events were mild or moderate. DISCUSSION: This novel formulation of
IBUNa provided superior overall PR compared with placebo and more rapid onset of
analgesic effect compared with standard IBU tablets. Rapid PR is important in the
treatment of acute pain, including dental pain, and this IBUNa formulation
represents a new treatment option for rapid PR.
PMID- 25119513
TI - Does Change Occur for the Reasons We Think It Does? A Test of Specific
Therapeutic Operations During Cognitive-Behavioral Treatment of Chronic Pain.
AB - OBJECTIVE: To examine the relative validity of 2 conceptual models-Specific,
General-by which therapeutic mechanisms in cognitive-behavioral therapy (CBT) for
chronic pain achieve favorable outcomes. METHODS: As part of a clinical trial of
enhanced versus standard CBT, people with chronic pain received treatment
consisting of 3 pain coping skill modules. In secondary analyses of a subsample
(n=56), we examined pretreatment to session 4 (of 10 sessions) changes in Chronic
Pain Coping Inventory subscales that corresponded to receipt of one of 3 modules;
namely Relaxation, Exercise, and Cognitive Coping modules. RESULTS: Findings
indicated that: (1) participants receiving the Relaxation module improved more
than other groups in relaxation skills, and improved substantially on other
coping skills, as well; (2) participants receiving Exercise and Cognitive Coping
modules showed mixed improvements and did not improve more than other groups on
exercise use or cognitive coping, respectively; and (3) measures of patient
therapist working alliance and patient expectations of treatment benefit at
session three correlated significantly with some coping skills changes.
DISCUSSION: Change with CBT may occur both by theory-specified mechanisms and
general mechanisms. However, the results provide the most support for a General
Mechanism model in which changes on coping skills have spreading effects on the
use of other coping skills. Significant relationships between some skill changes
and indexes of patient-therapist working alliance and outcome expectations
suggest that nonspecific factors also play a role in treatment-related changes in
the use of pain coping strategies.
PMID- 25119514
TI - Living Life With My Child's Pain: The Parent Pain Acceptance Questionnaire
(PPAQ).
AB - OBJECTIVE: Parents' emotional, cognitive, and behavioral responses are highly
influential on children's pain and functional outcomes. One important response to
pediatric pain is acceptance: the degree to which an individual participates in
routine daily activities in the presence of pain and is willing to let pain be a
part of their life without efforts to control or avoid it. However, no tool
currently exists to assess parents' own acceptance of their child's pain. The aim
of this study was to validate the Parent Pain Acceptance Questionnaire (PPAQ).
MATERIALS AND METHODS: The PPAQ was administered to 310 parents of youth with
chronic pain in an outpatient pediatric headache program and a day hospital pain
rehabilitation program. An exploratory factor analysis revealed 2 factors for the
PPAQ: an 11-item Activity Engagement scale and a 4-item Acceptance of Pain
related Thoughts and Feelings scale. RESULTS: The PPAQ total score and subscales
demonstrated strong internal consistency. Greater parent pain acceptance was
positively associated with child pain acceptance, and was negatively correlated
with parent protective behaviors, parent minimizing behaviors, parent and child
pain catastrophizing, and child fear of pain. Parent protective behaviors and
child pain acceptance both served as mediators of the relationship between parent
pain acceptance and child functional disability. CONCLUSIONS: The PPAQ is a valid
measure of parent pain acceptance and may provide valuable insights into parent
responses to child pain and the ways in which parent acceptance influences child
outcomes. Clinical implications and suggestions for future research are
discussed.
PMID- 25119515
TI - The impacts of information about the risks and benefits of pork consumption on
Chinese consumers' perceptions towards, and intention to eat, pork.
AB - This study investigates the impacts of information on the benefits and risks of
eating pork on Chinese consumers' attitudes and intentions. Data were collected
in March 2013 through a consumer survey (n=909) in Beijing and Baoding City. An
experiment was conducted using three types of message (positive, negative, and
balanced) combined with three information sources (government, research
institutes, and the pork industry). Participants ate pork almost every second
day. They perceived pork as rather nutritious and relatively expensive and had
neutral views about its healthiness and safety. Exposure to negative information
(about risks only) resulted in a significant and negative change in consumers'
perceptions of pork's nutritional value, price, healthiness and safety, while
exposure to positive information (about benefits only) caused a positive change
in consumers' perceptions about pork's healthiness and safety. Exposure to
balanced information resulted in a significant and negative change in the
perceived nutritional value of pork. Participants' intended frequency of pork
consumption was significantly lower after exposure to information, irrespective
of the type of information received. Exposure to risks-only information decreased
consumers' intention to eat pork, while exposure to benefit-only information had
a positive effect on consumers' intentions to eat pork. Exposure to balanced
risk/benefit information had no effect on intended pork consumption. Of the
information used, governmental materials were found to have a positive impact on
consumers' perceptions of pork's safety. Implications for communication
strategies with Chinese consumers about pork consumption are discussed.
PMID- 25119516
TI - Complete sequence analysis of mitochondrial DNA and telomere length in aplastic
anemia.
AB - The present study was primarily undertaken to examine the hypothesis that
mitochondrial DNA (mtDNA) mutations and telomere length may be associated with
aplastic anemia (AA). Our study included a single institution analysis of 40
patients presenting with AA first diagnosed at the Affiliated Hospital of
Shandong, University of Traditional Chinese Medicine between 2010 and 2013. Bone
marrow and oral epithelial samples were collected from patients with AA (n=40)
for mtDNA mutation and telomere length determinations. Bone marrow specimens were
collected from 40 healthy volunteers as controls for the examination of telomere
length. The mitochondrial genome was amplified by polymerase chain reaction
(PCR), and the products were used for sequencing and analysis. We detected 146
heteroplasmic mutations in 18 genes from 40 patients with AA, including 39 silent
mutations and 28 frameshift mutations. We used the gamma globin gene (HBG) as the
control gene in real-time PCR to survey the relative telomere length measurements
of the patients with AA and the healthy volunteers. Telomere length was expressed
as the relative T/S value. We observed a negative correlation between the mtDNA
non-silent mutation and the white blood cell (WBC) count, hemoglobin and platelet
count. Of note, there was a positive correlation between the relative T/S value
and WBC count, hemoglobin and platelet count, and a negative correlation between
the non-silent mutation and the relative T/S value. We conclude that the
functional impairment of the mitochondrial respiratory chain induced by mutation
and telomere length shortening may play an important role in the process of
hematopoietic failure in patients with AA. Additionally, mtDNA mutations and
telomere length shortening influenced each other.
PMID- 25119518
TI - Supplement use by UK-based British Army soldiers in training.
AB - The use of supplements is widespread at all levels of civilian sport and a
prevalence of 60-90 % is reported among high-performance UK athletes, including
juniors. The prevalence of supplement use among UK-based British Army personnel
is not known. The aim of the present study was to establish the point prevalence
of supplement use in UK-based British Army soldiers under training (SuTs) and
associated staff. A cross-sectional anonymous survey was carried out in 3168
British Army SuTs and soldiers, equating to 3.1 % of regular Army strength, based
at eleven Phase 1, 2 and 3 UK Army training sites. Overall, 38 % of the
respondents reported current use of supplements, but prevalence varied according
to the course attended by the respondents. The number of different supplements
used was 4.7 (sd 2.9). Supplements most commonly used were protein bars, powders
and drinks (66 %), isotonic carbohydrate-electrolyte sports drinks (49 %),
creatine (38 %), recovery sports drinks (35 %), multivitamins (31 %) and vitamin
C (25 %). A small proportion of respondents reported the use of amphetamines and
similar compounds (1.6 %), cocaine (0.8 %), anabolic androgenic steroids (1.1 %),
growth hormone (2.0 %), and other anabolic agents, e.g. testosterone (4.2 %).
Logistic regression modelling indicated that, for current users, younger age,
being female, smoking and undergoing Officer Cadet training were associated with
greater supplement use. This is the first study to investigate the prevalence of
dietary and training supplement use in UK-based British military personnel. Self
administration of a wide range of supplements is reported by British military
personnel in training, which is at least as great as that reported by those on
deployment, and has implications for Defence policy and educational needs.
PMID- 25119519
TI - Cold region bioremediation of hydrocarbon contaminated soils: do we know enough?
PMID- 25119521
TI - Patterns in the use of low-dose acetylsalicylic acid and other therapies
following upper gastrointestinal bleeding.
AB - BACKGROUND: Anticoagulants and/or antiplatelet agents such as acetylsalicylic
acid (ASA) are important in prevention of cardiovascular (CV) events, but may be
associated with upper gastrointestinal bleeding (UGIB). However, discontinuing
these agents may leave patients at risk of CV events. OBJECTIVES: This study
aimed to assess patterns of therapy after UGIB in routine clinical practice.
METHODS: The Health Improvement Network UK primary care database was used to
identify a cohort of patients aged 40-84 years with a UGIB event between 2000 and
2007 (n = 2,036). Patients were followed up for 1 year from the recorded UGIB. Re
prescription rates for antithrombotics and drugs that can modify the risk of UGIB
were estimated at 30, 90, 180, and 365 days. RESULTS: At 365 days, the re
prescription rate was 43 % for ASA, 66 % for warfarin, 69 % for clopidogrel, and
49 % for dipyridamole. The re-prescription rate of gastroprotective agents at 365
days for current users of histamine H2-receptor antagonists was 36 % and that of
proton pump inhibitors (PPIs) was 97 %. In patients who were prescribed ASA
before UGIB (n = 572), only 24 % were prescribed a PPI in the previous year. In
patients who were prescribed ASA in the year after UGIB (n = 337), 92 % were
prescribed a PPI. CONCLUSIONS: Antiplatelet use fell after UGIB events. In
patients who were prescribed a PPI after a UGIB event, there was increased re
prescription of antiplatelet agents and antithrombotics.
PMID- 25119522
TI - 5'-Guanosine monophosphate mediated biocompatible porous hydrogel of beta-FeOOH
viscoelastic behavior, loading, and release capabilities of freeze-dried gel.
AB - The present manuscript reports the characterization, optimization of rheological
properties, and loading and release capabilities of 5'-GMP mediated beta-FeOOH
hydrogel. Circular dichroism (CD) analysis indicates it to contain mainly the
left-handed helix similar to that of Z-DNA. The highest viscosity (>300 cP)
corresponds to the sample containing 2.5 * 10(-3) mol dm(-3) of 5'-GMP (SP2H).
Field emission scanning electron microscope (FESEM) and transmission electron
microscope (TEM) studies indicate the freeze-dried (FD) SP2H to be porous in
nature, which is also supported by its high Brunauer-Emmett-Teller (BET) surface
area of 226 m(2)/g as compared to that of SP3H (75 m(2)/g). Selected area
electron diffraction (SAED) analysis and Raman spectroscopy show it to contain
beta-FeOOH phase. The FD SP2H exhibits the high swelling ratio (326%) and loading
capacity for methylene blue (MB) dye. It displays a controlled and efficient
release (>90%) for optimized [MB] (2.5 * 10(-4) mol dm(-3)) in 48 h. The low
toxicity of as synthesized FD SP2H nanostructures against MDA-MB-231 (breast
cancer cells) up to 100 MUg/mL suggests its biocompatible nature. The high
porosity, surface area, % swelling, and loading and release performance of the
hydrogel indicate its potential for drug delivery and other biological
applications.
PMID- 25119523
TI - Transition-metal-free tandem oxidative removal of benzylic methylene group by C-C
and C-N bond cleavage followed by intramolecular new aryl C-N bond formation
under radical conditions.
AB - A novel tandem oxidative conversion of 10,11-dihydro-5H
dibenzo[b,e][1,4]diazepines to phenazines has been achieved under transition
metal-free, mild conditions using K2S2O8 or DDQ as the oxidizing agent. The
transformation proceeds through oxidative removal of a benzylic methylene group
by C-C and C-N bond cleavage followed by a new aryl C-N bond formation under
radical conditions.
PMID- 25119520
TI - Self-titrating anticoagulant nanocomplexes that restore homeostatic regulation of
the coagulation cascade.
AB - Antithrombotic therapy is a critical portion of the treatment regime for a number
of life-threatening conditions, including cardiovascular disease, stroke, and
cancer; yet, proper clinical management of anticoagulation remains a challenge
because existing agents increase the propensity for bleeding in patients. Here,
we describe the development of a bioresponsive peptide-polysaccharide nanocomplex
that utilizes a negative feedback mechanism to self-titrate the release of
anticoagulant in response to varying levels of coagulation activity. This
nanoscale self-titrating activatable therapeutic, or nanoSTAT, consists of a
cationic thrombin-cleavable peptide and heparin, an anionic polysaccharide and
widely used clinical anticoagulant. Under nonthrombotic conditions, nanoSTATs
circulate inactively, neither releasing anticoagulant nor significantly
prolonging bleeding time. However, in response to life-threatening pulmonary
embolism, nanoSTATs locally release their drug payload and prevent thrombosis.
This autonomous negative feedback regulator may improve antithrombotic therapy by
increasing the therapeutic window and decreasing the bleeding risk of
anticoagulants.
PMID- 25119524
TI - Homogeneous photochemical water oxidation by biuret-modified Fe-TAML: evidence of
Fe(V)(O) intermediate.
AB - Water splitting, leading to hydrogen and oxygen in a process that mimics natural
photosynthesis, is extremely important for devising a sustainable solar energy
conversion system. Development of earth-abundant, transition metal-based
catalysts that mimic the oxygen-evolving complex of photosystem II, which is
involved in oxidation of water to O2 during natural photosynthesis, represents a
major challenge. Further, understanding the exact mechanism, including
elucidation of the role of active metal-oxo intermediates during water oxidation
(WO), is critical to the development of more efficient catalysts. Herein, we
report Fe(III) complexes of biuret-modified tetra-amidomacrocyclic ligands (Fe
TAML; 1a and 1b) that catalyze fast, homogeneous, photochemical WO to give O2,
with moderate efficiency (maximum TON = 220, TOF = 0.76 s(-1)). Previous studies
on photochemical WO using iron complexes resulted in demetalation of the iron
complexes with concomitant formation of iron oxide nanoparticles (NPs) that were
responsible for WO. Herein, we show for the first time that a high valent
Fe(V)(O) intermediate species is photochemically generated as the active
intermediate for the oxidation of water to O2. To the best of our knowledge, this
represents the first example of a molecular iron complex catalyzing photochemical
WO through a Fe(V)(O) intermediate.
PMID- 25119527
TI - Perturbation of the charge density between two bridged Mo2 centers: the remote
substituent effects.
AB - A series of terephthalate-bridged dimolybdenum dimers with various formamidinate
ancillary ligands, denoted as [Mo2(ArNCHNAr)3]2(MU-O2CC6H4CO2) (Ar = p-XC6H4,
with X = OCH3 (1), CH3 (2), F (3), Cl (4), OCF3 (5), and CF3 (6)), has been
synthesized and studied in terms of substituent effects on electron
delocalization between the two dimetal sites. X-ray structural analyses show that
these complexes share the same molecular scaffold with the para-substituents (X)
being about 8 A away from the Mo2 center. It is found that the remote
substituents have the capability to tune the electronic properties of the
complexes. For the series 1 to 6, the metal-metal bond distances (d(Mo-Mo))
decrease slightly and continuously; the potential separations (DeltaE(1/2)) for
the two successive one-electron oxidations decrease constantly, and the metal to
ligand transition energies (lambda(max)) increase in order. More interestingly,
the two types of methine protons, H(?) on the horizontal and H(?) on the vertical
ligands with respect to the plane defined by the Mo-Mo bond vectors and bridging
ligand, display separate resonant signals delta(?) and delta(?) in the NMR
spectra. The displacements of the chemical shifts, Deltadelta(?-?) = delta(?) -
delta(?), are getting smaller as the substituents vary from electron-donating to
withdrawing. These results show that the peripheral groups on the [Mo2] units
function to fine-tune the metal-metal interactions crossing the bridging ligand.
The experimental parameters, DeltaE(1/2), lambda(max), and Deltadelta(?-?), which
are linearly related with the Hammett constants (sigma(X)) of the X groups, can
be used to probe the charge density on the two [Mo2] units and the electronic
delocalization between them.
PMID- 25119526
TI - In silico analysis of missense mutations in LPAR6 reveals abnormal phospholipid
signaling pathway leading to hypotrichosis.
AB - Autosomal recessive hypotrichosis is a rare genetic irreversible hair loss
disorder characterized by sparse scalp hair, sparse to absent eyebrows and
eyelashes, and sparse axillary and body hair. The study, presented here,
established genetic linkage in four families showing similar phenotypes to
lysophosphatidic acid receptor 6 (LPAR6) gene on chromosome 13q14.11-q21.32.
Subsequently, sequence analysis of the gene revealed two previously reported
missense mutations including p.D63V in affected members of one and p.I188F in
three other families. Molecular modeling and docking analysis was performed to
investigate binding of a ligand oleoyl-L-alpha-lysophosphatidic acid (LPA) to
modeled protein structures of normal and mutated (D63V, G146R, I188F, N248Y, S3T,
L277P) LPAR6 receptors. The mutant receptors showed a complete shift in
orientation of LPA at the binding site. In addition, hydropathy analysis revealed
a significant change in the membrane spanning topology of LPAR6 helical segments.
The present study further substantiated involvement of LPAR6-LPA signaling in the
pathogenesis of hypotrichosis/woolly hair and provided additional insight into
the molecular mechanism of hair development.
PMID- 25119525
TI - The disorganized visual cortex in reelin-deficient mice is functional and allows
for enhanced plasticity.
AB - A hallmark of neocortical circuits is the segregation of processing streams into
six distinct layers. The importance of this layered organization for cortical
processing and plasticity is little understood. We investigated the structure,
function and plasticity of primary visual cortex (V1) of adult mice deficient for
the glycoprotein reelin and their wild-type littermates. In V1 of rl-/- mice,
cells with different laminar fates are present at all cortical depths.
Surprisingly, the (vertically) disorganized cortex maintains a precise
retinotopic (horizontal) organization. Rl-/- mice have normal basic visual
capabilities, but are compromised in more challenging perceptual tasks, such as
orientation discrimination. Additionally, rl-/- animals learn and memorize a
visual task as well as their wild-type littermates. Interestingly, reelin
deficiency enhances visual cortical plasticity: juvenile-like ocular dominance
plasticity is preserved into late adulthood. The present data offer an important
insight into the capabilities of a disorganized cortical system to maintain basic
functional properties.
PMID- 25119528
TI - Screening of beta-secretase and acetylcholinesterase inhibitors from plant
resources.
AB - The therapeutic agents for dementia are limited due to the complex system
underlying the mechanisms. Taking a preventive point of view, we focused on the
inhibition of beta-secretase and acetylcholinesterase (AChE). In addition, plant
resources including herbs and spices have been widely consumed, and further, may
be consumed for a long period over a lifetime. Considering this background, we
screened beta-secretase and AChE inhibitors from curry spices. Amongst them,
curry leaf, black pepper, and turmeric extracts were effective to inhibit beta
secretase. Furthermore, black pepper and turmeric extracts were also effective to
inhibit AChE. Having these results in hand, we focused on the investigation of
beta-secretase inhibitors since the inhibitor of this enzyme has not previously
been well investigated. As a result, alpha- and beta-caryophyllene, beta
caryophyllene oxide (from curry leaf), piperine (from black pepper), curcumin,
demethoxycurcumin, and bisdemethoxycurcumin (from turmeric) were successfully
identified as low molecular inhibitors. This is the first report to determine
alpha- and beta-caryophyllene, beta-caryophyllene oxide, and piperine as beta
secretase inhibitors. These compounds may pass through the blood brain barrier
since their molecular weights are relatively low.
PMID- 25119529
TI - Enhanced ultra-low-frequency interlayer shear modes in folded graphene layers.
AB - Few-layer graphene has attracted tremendous attention owing to its exceptional
electronic properties inherited from single-layer graphene and new features led
by introducing extra freedoms such as interlayer stacking sequences or rotations.
Effectively probing interlayer shear modes are critical for unravelling
mechanical and electrical properties of few-layer graphene and further developing
its practical potential. Unfortunately, shear modes are extremely weak and almost
fully blocked by a Rayleigh rejecter in Raman measurements. This greatly hinders
investigations of shear modes in few-layer graphene. Here, we demonstrate
enhancing of shear modes by properly folding few-layer graphene. As a direct
benefit of the strong signal, enhancement mechanism, vibrational symmetry,
anharmonicity and electron-phonon coupling of the shear modes are uncovered
through studies of Raman mapping, polarization- and temperature-dependent Raman
spectroscopy. This work complements Raman studies of graphene layers, and paves
an efficient way to exploit low-frequency shear modes of few-layer graphene and
other two-dimensional layered materials.
PMID- 25119530
TI - Contrasting behavior of heterochromatic and euchromatic chromosome portions and
pericentric genome separation in pre-bouquet spermatocytes of hybrid mice.
AB - The spatial distribution of parental genomes has attracted much interest because
intranuclear chromosome distribution can modulate the transcriptome of cells and
influence the efficacy of meiotic homologue pairing. Pairing of parental
chromosomes is imperative to sexual reproduction as it translates into homologue
segregation and genome haploidization to counteract the genome doubling at
fertilization. Differential FISH tagging of parental pericentromeric genome
portions and specific painting of euchromatic chromosome arms in Mus musculus
(MMU) * Mus spretus (MSP) hybrid spermatogenesis disclosed a phase of homotypic
non-homologous pericentromere clustering that led to parental pericentric genome
separation from the pre-leptoteneup to zygotene stages. Preferential clustering
of MMU pericentromeres correlated with particular enrichment of epigenetic marks
(H3K9me3), HP1-gamma and structural maintenance of chromosomes SMC6 complex
proteins at the MMU major satellite DNA repeats. In contrast to the separation of
heterochromatic pericentric genome portions, the euchromatic arms of homeologous
chromosomes showed considerable presynaptic pairing already during leptotene
stage of all mice investigated. Pericentric genome separation was eventually
disbanded by telomere clustering that concentrated both parental pericentric
genome portions in a limited nuclear sector of the bouquet nucleus. Our data
disclose the differential behavior of pericentromeric heterochromatin and the
euchromatic portions of the parental genomes during homologue search. Homotypic
pericentromere clustering early in prophase I may contribute to the exclusion of
large repetitive DNA domains from homology search, while the telomere bouquet
congregates and registers spatially separated portions of the genome to fuel
synapsis initiation and high levels of homologue pairing, thus contributing to
the fidelity of meiosis and reproduction.
PMID- 25119534
TI - Seasonal variation and source apportionment of organic tracers in PM10 in
Chengdu, China.
AB - Organic compound tracers including n-alkanes, triterpane, sterane, polycyclic
aromatic hydrocarbons (PAHs) and dicarboxylic acids of airborne particulate
matter (PM10) were characterized for samples collected at five sites from July
2010 to March 2011 using GC/MS. Spatial and temporal variations of these organic
tracers in PM10 were studied, and their sources were then identified
respectively. Average daily concentrations of PM10 varied in different seasons
with the trend of PM10 in winter (0.133 mg/m(3)) > autumn (0.120 mg/m(3)) >
spring (0.103 mg/m(3)) > summer (0.098 mg/m(3)). Daily concentrations of n
alkanes (C11-C36) ranged from 12.11 to 163.58 ng/m(3) with a mean of 61.99
ng/m(3). The C max and CPI index of n-alkanes indicated that vehicle emissions
were the major source in winter, while the contributions of high plant wax
emissions became significant in other seasons. It was discovered that the main
sources of triterpenoid and steranes were gasoline and diesel engine emissions.
Concentrations of ?15PAHs in PM10 also varied (12.25-58.56 ng/m(3)) in different
seasons, and chrysene, benzo(a)pyrene, benzo(b)fluoranthene,
benzo(k)fluoranthene, benzo(ghi) perylene and fluoranthene were the dominant
components. In the four seasons, the concentration of ?15PAHs was relatively
higher at the northern site because of traffic congestion. The main source of
airborne PAHs was traffic emissions and coal combustion. Average daily
concentrations of dicarboxylic acids (C4-C10) in PM10 ranged from 12.11 to 163.58
ng/m(3), of which azeleic acid was the major compound (0.49-52.04 ng/m(3),
average 14.93 ng/m(3)), followed by succinic acid (0.56-19.08 ng/m(3), average
6.84 ng/m(3)). The ratio of C6/C9 showed that the major source in winter was
biological, while the contributions of emissions from anthropogenic activities
were much higher in summer.
PMID- 25119532
TI - Comorbidities among the HIV-infected patients aged 40 years or older in Taiwan.
AB - BACKGROUND: With the widespread use of combination antiretroviral therapy (cART),
life expectancy of HIV-infected patients has significantly prolonged. An
increasing number of HIV-infected patients are aging and concurrent use of
medications are not uncommon for management of metabolic complications and
cardiovascular diseases related to aging and prolonged exposure to cART. METHODS:
We reviewed medical records of all HIV-infected patients aged 40 years or older
who had been followed at a university hospital for HIV care in Taiwan between
January and December 2013. A standardized case record form was used to collect
information on demographics and clinical characteristics, comorbidity, cART, and
concurrent medications. RESULTS: During the study period, 610 patients aged 40 to
49 years (mean, 44.1) and 310 aged 50 years or older (mean, 58.8) sought HIV care
at this hospital. Compared with patients aged 40 to 49 years, those aged 50 years
or older were significantly more likely to be female (15.9% vs 3.8%); to have
received cART (97.7% vs 94.8%) and a lower plasma HIV RNA load (1.6 vs 1.7 log10
copies/ml); and to have diabetes mellitus (18.4% vs 4.6%), hypertension (31.0% vs
10.8%), hyperlipidemia (29.4% vs 11.6%), coronary artery disease (6.8% vs 0.5%),
and an estimated glomerular filtration rate <60 ml/min/1.73 m2 (11.5% vs 2.7%);
and were significantly less likely to have syphilis. Other than HIV infection,
patients aged 50 years or older were more likely to have been receiving two or
more concurrent medications than those aged 40 to 49 years (22.9% vs 6.4%).
CONCLUSIONS: Our findings show a significant proportion of the HIV-infected
patients aged 50 years or older have multiple comorbidities that may increase the
risk for cardiovascular and renal complications. Issues of poly-pharmacy among
the HIV-infected patients who are aging should be addressed to ensure adherence
and minimize drug-drug interactions.
PMID- 25119535
TI - Chronic kidney disease of unknown aetiology and ground-water ionicity: study
based on Sri Lanka.
AB - High incidence of chronic kidney disease of unknown aetiology (CKDU) in Sri Lanka
is shown to correlate with the presence of irrigation works and rivers that bring
in 'nonpoint source' fertilizer runoff from intensely agricultural regions. We
review previous attempts to link CKDU with As, Cd and other standard toxins.
Those studies (e.g. the WHO-sponsored study), while providing a wealth of data,
are inconclusive in regard to aetiology. Here, we present new proposals based on
increased ionicity of drinking water due to fertilizer runoff into the river
system, redox processes in the soil and features of 'tank'-cascades and aquifers.
The consequent chronic exposure to high ionicity in drinking water is proposed to
debilitate the kidney via a Hofmeister-type (i.e. protein-denaturing) mechanism.
PMID- 25119537
TI - [Femoral nailing using a helical nail shape (LFN((r)))].
AB - OBJECTIVE: Antegrade femoral nailing through a greater trochanteric entry portal
avoids damage to the proximal external rotators and to the ramus profundus of the
medial femoral circumflex artery, furthermore eases insertion in adipose
subjects. However a helical nail shape is necessary for this pathway because
bending in two perpendicular planes has to be passed by the nail. INDICATIONS:
All femoral shaft fractures suitable for antegrade nailing (type 32-A/B/C).
Additional femoral neck fractures (type 31-B) by using proximal Recon
interlocking screws. CONTRAINDICATIONS: The common contraindications for femoral
nailing. In certain subtrochanteric fractures (Type 32-A/B) the proximal femoral
nail may be favorable. SURGICAL TECHNIQUE: General or spinal anesthesia. Supine
position with flexion/abduction of the contralateral leg in order to facilitate
fluoroscopy of the proximal femur in a true lateral view. Closed reduction of
length and axis. Measurement of length and diameter of the nail using a
radiolucent ruler. Dorsolateral approach to the greater trochanter. Insertion of
the guide wire 10 mm lateral to the trochanteric tip (anteroposterior view) and
in the middle third of the trochanter (lateral view). Reaming of the insertion
point using a flexible reamer. If reaming of the entire medullary canal is
desired, this should be done using a long intramedullary guide wire in
combination with a long flexible reamer. Insertion of the nail starts in an
anterior position and ends in a lateral position of the insertion instrument, so
a 90 degrees external rotation of the nail occurs during insertion. Proximal
interlocking is performed using the guide of the insertion instrument. Check
interfragmentary rotation. Distal interlocking using a radiolucent drill device.
POSTOPERATIVE MANAGEMENT: Depends on the fracture shape: stable interfragmentary
support may allow early full weight bearing. Otherwise, reduced weight bearing is
recommended for at least 6 weeks. RESULTS: In a prospective mulicentric study,
227 helical femoral nails were used for antegrade femoral nailing. Follow-up
after 12 month was available in 74 %. Surgeons' rating for ease of identifying
entry site was excellent or good in 89 %. Functional and radiological results
after 12 months do not prove significant benefits over conventional antegrade
femoral nails.
PMID- 25119538
TI - Lysophosphatidic acid induces anxiety-like behavior via its receptors in mice.
AB - Lysophosphatidic acid (LPA) is a potent bioactive lipid mediator with diverse
biological properties. We previously found altered expression of the LPA-related
genes in rodents after treatment with sertraline, which is widely used to treat
anxiety disorders and depression. However, little is known about the behavioral
effects of LPA. In the present study, we investigated the behavioral effects of
intracerebroventricular injection of LPA in adult mice. LPA did not significantly
affect spontaneous locomotor activity, suggesting that LPA does not induce
hyperactivity, ataxia, or sedation. We next investigated the emotional effects of
LPA via the hole-board test. LPA significantly increased the number of head-dips
in a dose- and time-related manner. A significant induction of head-dip counts
occurred 15 and 30 min after LPA administration. To clarify the involvement of
LPA receptors, we examined the effect of the non-selective LPA1-4 receptor
antagonist, 1-bromo-3(S)-hydroxy-4-(palmitoyloxy)butyl-phosphonate (BrP-LPA) co
administered with LPA. BrP-LPA dose-dependently inhibited LPA-induced head-dip
counts. We next investigated anxiety-like behavior via the elevated plus-maze
test. LPA significantly reduced the percentage of time spent in the open arms and
BrP-LPA dose-dependently inhibited this anxiety-like behavior. In conclusion, LPA
induced anxiety-like behavior in mice via LPA receptors. Our results suggest that
LPA signaling plays an important role in regulating anxiety in mice.
PMID- 25119536
TI - The Hepatocyte Growth Factor (HGF)/Met Axis: A Neglected Target in the Treatment
of Chronic Myeloproliferative Neoplasms?
AB - Met is the receptor of hepatocyte growth factor (HGF), a cytoprotective cytokine.
Disturbing the equilibrium between Met and its ligand may lead to inappropriate
cell survival, accumulation of genetic abnormalities and eventually, malignancy.
Abnormal activation of the HGF/Met axis is established in solid tumours and in
chronic haematological malignancies, including myeloma, acute myeloid leukaemia,
chronic myelogenous leukaemia (CML), and myeloproliferative neoplasms (MPNs). The
molecular mechanisms potentially responsible for the abnormal activation of
HGF/Met pathways are described and discussed. Importantly, inCML and in MPNs, the
production of HGF is independent of Bcr-Abl and JAK2V617F, the main molecular
markers of these diseases. In vitro studies showed that blocking HGF/Met function
with neutralizing antibodies or Met inhibitors significantly impairs the growth
of JAK2V617F-mutated cells. With personalised medicine and curative treatment in
view, blocking activation of HGF/Met could be a useful addition in the treatment
of CML and MPNs for those patients with high HGF/MET expression not controlled by
current treatments (Bcr-Abl inhibitors in CML; phlebotomy, hydroxurea, JAK
inhibitors in MPNs).
PMID- 25119540
TI - A prospective, randomized, controlled trial of the postoperative analgesic
effects of spraying 0.25 % levobupivacaine after bilateral axillo-breast approach
robotic thyroidectomy.
AB - BACKGROUND: Robotic thyroidectomy (RoT) is frequently performed due to its
excellent cosmesis and recovery features. However, postoperative pain in the
operating field after RoT remains a concern due to extensive tissue dissection
and tension during the operation. The aim of this study was to evaluate the
anterior chest pain and the effect of levobupivacaine spraying on postoperative
pain control after bilateral axillo-breast approach (BABA) RoT. METHODS: We
randomized 55 adult patients scheduled for BABA RoT into the control group (group
C, n = 27) or the levobupivacaine group (group L, n = 28). At the end of surgery,
patients in groups C and L were sprayed with the same volume (30 ml) of normal
saline and 0.25 % levobupivacaine, respectively, on the flap dissection area.
Pain scores, the consumption of patient-controlled analgesia (PCA), and other
adverse effects were assessed at 1, 6, 24, and 48 h postoperatively. RESULTS:
Patients in group L showed lower pain scores than those of group C at 1 h (50 [0
100] vs. 80 [20-100]; p = 0.004), 6 h (30 [0-90] vs. 70 [30-90]; p < 0.001), 24 h
(30 [0-80] vs. 50 [10-80]; p = 0.016) and 48 h (10 [0-80] vs. 30 [10-80]; p <
0.001) postoperatively. PCA consumption of group L was less than that of group C
at 6, 24, and 48 h after surgery. There were no significant differences in
postoperative nausea-vomiting, headache, or dizziness. Local anesthetic-related
adverse effects were not reported. CONCLUSION: Levobupivacaine spray on the
operative field at the end of BABA RoT reduced postoperative pain and PCA
consumption without adverse events.
PMID- 25119539
TI - Common mechanisms in neurodegeneration and neuroinflammation: a BrainNet Europe
gene expression microarray study.
AB - Neurodegenerative diseases of the central nervous system are characterized by
pathogenetic cellular and molecular changes in specific areas of the brain that
lead to the dysfunction and/or loss of explicit neuronal populations. Despite
exhibiting different clinical profiles and selective neuronal loss, common
features such as abnormal protein deposition, dysfunctional cellular transport,
mitochondrial deficits, glutamate excitotoxicity, iron accumulation and
inflammation are observed in many neurodegenerative disorders, suggesting
converging pathways of neurodegeneration. We have generated comparative genome
wide gene expression data, using the Illumina HumanRef 8 Beadchip, for
Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease,
multiple sclerosis, Parkinson's disease, and schizophrenia using an extensive
cohort (n = 113) of well-characterized post-mortem brain tissues. The analysis of
whole-genome expression patterns across these major disorders offers an
outstanding opportunity not only to look into exclusive disease-specific changes,
but more importantly to look for potential common molecular pathogenic
mechanisms. Surprisingly, no dysregulated gene that passed our selection criteria
was found in common across all six diseases. However, 61 dysregulated genes were
shared when comparing five and four diseases. The few genes highlighted by our
direct gene comparison analysis hint toward common neuronal homeostatic, survival
and synaptic plasticity pathways. In addition, we report changes to several
inflammation-related genes in all diseases. This work is supportive of a general
role of the innate immune system in the pathogenesis and/or response to
neurodegeneration.
PMID- 25119542
TI - Magnetic lower esophageal sphincter augmentation device removal.
AB - Implantation of a magnetic lower esophageal sphincter augmentation device is now
an alternative to fundoplication in the surgical management of gastroesophageal
reflux disease (GERD). Although successful management of GERD has been reported
following placement of the device, there are instances when device removal is
needed. The details of the technique for laparoscopic magnetic lower esophageal
sphincter device removal are presented to assist surgeons should device removal
become necessary.
PMID- 25119541
TI - Systematic review of the clinical and cost effectiveness of cholecystectomy
versus observation/conservative management for uncomplicated symptomatic
gallstones or cholecystitis.
AB - BACKGROUND: Gallstone disease is a common gastrointestinal disorder in
industrialised countries. Although symptoms can be severe, some people can be
symptom free for many years after the original attack. Surgery is the current
treatment of choice, but evidence suggests that observation is also feasible and
safe. We reviewed the evidence on cholecystectomy versus observation for
uncomplicated symptomatic gallstones and conducted a cost-effectiveness analysis.
METHODS: We searched six electronic databases (last search April 2014). We
included randomised controlled trials (RCTs) or non-randomised comparative
studies where adults received either cholecystectomy or observation/conservative
management for the first episode of symptomatic gallstone disease (biliary pain
or cholecystitis) being considered for surgery in secondary care. Meta-analysis
was used to combine results. A de novo Markov model was developed to assess the
cost effectiveness of the interventions. RESULTS: Two RCTs (201 participants)
were included. Eighty-eight percent of people randomised to surgery and 45 % of
people randomised to observation underwent cholecystectomy during the 14-year
follow-up period. Participants randomised to observation were significantly more
likely to experience gallstone-related complications (RR = 6.69, 95 % CI = 1.57
28.51, p = 0.01), in particular acute cholecystitis (RR = 9.55, 95 % CI = 1.25
73.27, p = 0.03), and less likely to undergo surgery (RR = 0.50, 95 % CI = 0.34
0.73, p = 0.0004) or experience surgery-related complications (RR = 0.36, 95 % CI
= 0.16-0.81, p = 0.01) than those randomised to surgery. Fifty-five percent of
people randomised to observation did not require surgery, and 12 % of people
randomised to cholecystectomy did not undergo surgery. On average, surgery costs
L1,236 more per patient than conservative management, but was more effective.
CONCLUSIONS: Cholecystectomy is the preferred treatment for symptomatic
gallstones. However, approximately half the observation group did not require
surgery or suffer complications indicating that it may be a valid alternative to
surgery. A multicentre trial is needed to establish the effects, safety and cost
effectiveness of observation/conservative management relative to cholecystectomy.
PMID- 25119544
TI - Expression profiling of sucrose metabolizing genes in Saccharum, Sorghum and
their hybrids.
AB - Sucrose phosphate synthase (SPS; EC 2.4.1.14), sucrose synthase (SuSy; EC
2.4.1.13) and soluble acid invertase (SAI; EC 3.2.1.26) are key enzymes that
regulate sucrose fluxes in sink tissues for sucrose accumulation in sugarcane and
sorghum. In this study, the expression profiling of sucrose-related genes, i.e.
SPS, SuSy and SAI in two sets of hybrids viz., one from a Sorghum * Saccharum
cross and the other from a Saccharum * Sorghum cross, high- and low-sucrose
varieties, sweet and grain sorghum lines was carried out using semi-quantitative
reverse transcription-polymerase chain reaction (RT-PCR) at monthly intervals.
The results indicated differential expression of the three genes in high- and low
sucrose forms. Expression of SPS and SuSy genes was high in high-sucrose
varieties, Saccharum * Sorghum hybrids and sweet sorghum and lower in low-sucrose
varieties, Sorghum * Saccharum hybrids and grain sorghum. SAI showed a lower
expression in high-sucrose varieties, Saccharum * Sorghum hybrids and sweet
sorghum and higher expression in low-sucrose varieties, Sorghum * Saccharum
hybrids and the grain sorghum. This study describes the positive association of
SPS and SuSy and negative association of SAI on sucrose accumulation. This is the
first report of differential expression profiling of SPS, SuSy and SAI in
intergeneric hybrids involving sugarcane and sorghum, which opens the possibility
for production of novel hybrids with improved sucrose content and with early
maturity.
PMID- 25119543
TI - Immunoadjuvant activity of the nanoparticles' surface modified with mannan.
AB - Mannan (MN) is the natural ligand for mannose receptors, which are widely
expressed on dendritic cells (DCs). The purpose of this study was to assess the
effect of formulation parameters on the immunogenicity of MN-decorated poly (D, L
lactide-co-glycolide) (PLGA) nanoparticles (NPs) in terms of their ability to
stimulate DC phenotypic as well as functional maturation. For this purpose, NPs
were formulated from either ester-terminated or COOH-terminated PLGA.
Incorporation of MN in NPs was achieved through encapsulation, physical
adsorption or chemical conjugation. Murine bone marrow derived DCs (BMDCs) were
treated with various NP formulations and assessed for their ability to up
regulate DC cell surface markers, secrete immunostimulatory cytokines and to
activate allogenic T cell responses. DCs treated with COOH-terminated PLGA-NPs
containing chemically conjugated MN (MN-Cov-COOH) have shown superior performance
in improving DC biological functions, compared to the rest of the formulations
tested. This may be attributed to the higher level of MN incorporation in the
former formulation. Incorporation of MN in PLGA NPs through chemical conjugation
can lead to enhanced DC maturation and stimulatory function. This strategy may be
used to develop more effective PLGA-based vaccine formulations.
PMID- 25119545
TI - Anti-bactericidal properties of stingray Dasyatis pastinaca groups V, IIA, and IB
phospholipases A2: a comparative study.
AB - Group IIA secreted phospholipase A2 (group IIA sPLA2) is known to display potent
Gram-positive bactericidal activity in vitro and in vivo. We have analyzed the
bactericidal activity of the full set of native stingray and dromedary groups V,
IIA, and IB sPLA2s on several Gram-positive and Gram-negative strains. The rank
order potency among both marine and mammal sPLA2s against Gram-positive bacteria
is group IIA > V > IB, whereas Gram-negative bacteria exhibited a much higher
resistance. There is a synergic action of the sPLA2 with lysozyme when added to
the bacteria culture prior to sPLA2.The bactericidal efficiency of groups V and
IIA sPLA2s was shown to be dependent upon the presence of calcium ions and to a
less extent Mg(2+) ions and then a correlation could be made to its hydrolytic
activity of membrane phospholipids. Importantly, we showed that stingray and
dromedary groups V, IIA, and IB sPLA2s present no cytotoxicity after their
incubation with MDA-MB-231cells. stingray groups V and IIA sPLA2s, like mammal
ones, may be considered as future therapeutic agents against bacterial
infections.
PMID- 25119546
TI - Development of optimal medium content for bioelements accumulation in Bacopa
monnieri (L.) in vitro culture.
AB - Bacopa monnieri is one of the most interesting plants from the Ayurveda system.
The aims of present research were, basing on in vitro shoot culture of B.
monnieri, to determine content and to evaluate the influence of physiologically
important metabolites on the selected bioelements accumulation in biomass. The
most significant increase in biomass production was observed in the culture
medium enriched with 0.5 mg/L of anthranilic acid. In this medium also, the
highest accumulation of Mg was noted. The highest concentration of iron was
determined in B. monnieri in vitro culture enriched with 0.25 g/L of serine. The
addition of L-tryptophan, magnesium sulfate, and zinc hydroaspartate caused only
a small increase in the accumulation of copper in B. monnieri. Increase in Zn
accumulation was obtained in biomass from in vitro culture of B. monnieri with
the addition of magnesium sulfate and zinc hydroaspartate. In the case of Na, the
maximum level of this element was in biomass from medium enriched with zinc
hydroaspartate. Twofold increase in K concentration was obtained in biomass from
cultures on medium with addition of serine and magnesium sulfate. The
concentrations of Ca in biomass of all studied media were at the similar level.
PMID- 25119547
TI - Genome shuffling enhances lipase production of thermophilic Geobacillus sp.
AB - Thermostable lipases are potential enzymes for biocatalytic application. In this
study, the lipase production of Geobacillus sp. CF03 (WT) was improved by genome
shuffling. After two rounds of genome shuffling, one fusant strain (FB1) achieved
increase lipase activity from the populations generated by ultraviolet
irradiation and ethyl methylsulfonate (EMS) mutagenesis. The growth rate and
lipase production of FB1 increased highest by 150 and 238 %, respectively, in
comparison to the wild type. The fusant enzyme had a significant change in
substrate specificity but still prefers the long-chain length substrates. It had
an optimum activity at 60 degrees C, pH at 7.0-8.0, with p-nitrophenyl palmitate
(C16) as a substrate and retained about 50 % of their activity after 15 min at 70
degrees C, pH 8.0. Furthermore, the fusant lipase showed the preference of
sesame oil, waste palm oil, and canola oil. Therefore, the genome shuffling
strategy has been successful to strain improvement and selecting strain with
multiple desirable characteristics.
PMID- 25119548
TI - Lipid production of microalga Ankistrodesmus falcatus increased by nutrient and
light starvation in a two-stage cultivation process.
AB - The aim of this work was to study the stimulation of lipid production on the
microalga Ankistrodesmus falcatus by varying cultivation conditions during the
stationary phase. The effect of three factors (presence and absence of nitrogen,
phosphorus, and light) has been tested once the cultures reached the stationary
phase with the aim to increase the value of the biomass for further applications.
Lipid content, elemental composition, Nile red fluorescence evolution, and
calorific value of microalgal biomass were studied as well as biomass growth.
Biomass presented a lipid content of 36.54 % at the end of the first stage, while
at the end of the second stage, the experiments with the absence of phosphorus
increased their lipid content until 45.94 and 44.55 %, the first with nitrogen
and light presence and the second with absence of all factors. The combination of
phosphorus absence and nitrogen and light presence achieved the highest lipid
productivity (20.27 mg/L/day). The two-stage strategy to culture microalgae is a
feasible option to increase the economic or energetic value of biomass.
PMID- 25119549
TI - The application of the Biolog EcoPlate approach in ecotoxicological evaluation of
dairy sewage sludge.
AB - An increasing amount of sewage sludge requires reasonable management, whereas its
storage might be environmentally hazardous. Due to the organic matter and
nutrient presence in sediments, it may be used as organic fertilizer. However,
beyond the valuable contests, sewage sludge can also contain toxic or dangerous
ingredients like heavy metals. Therefore, there is a need to develop methods for
rapid assessment of sediment ecotoxicity that will determine its possible
applicability in agriculture. The Biolog(r) EcoPlate enables the metabolic
profile diversity evaluation of microbial populations in environmental samples,
which reflects the state of their activity. It is regarded as a modern technology
that by means of biological properties allows quick characterization of the
ecological status of environmental samples, such as sewage sludge.
PMID- 25119550
TI - Continuous esterification of free fatty acids in crude biodiesel by an integrated
process of supercritical methanol and sodium methoxide catalyst.
AB - An integrated process of supercritical methanol (SCM) and sodium methoxide
catalyst was developed to produce fatty acid methyl esters (FAMEs) via continuous
esterification from crude biodiesel. The crude biodiesel with high free fatty
acid (FFA) content must be refined to reduce the acid value (AV) for meeting the
quality standards. The process parameters were studied by Box-Behnken design
(BBD) of response surface methodology (RSM). The experimental results revealed
that the AV of crude biodiesel decreased from 18.66 to 0.55 mg KOH g(-1) at the
reaction conditions of 350 degrees C, 0.5 % amount of sodium methoxide catalyst,
and 10 MPa. Temperature shows the most significant effect on the esterification,
followed by pressure and amount of sodium methoxide catalyst. This integrated
process proved to be a potential route to refine the crude biodiesel because of
its continuity, high efficiency, and less energy consumption with relatively
moderate reaction conditions compared with conventional methods.
PMID- 25119551
TI - Effect of phytase application during high gravity (HG) maize mashes preparation
on the availability of starch and yield of the ethanol fermentation process.
AB - Phytic acid present in raw materials used in distilling industry can form
complexes with starch and divalent cations and thus limit their biological
availability. The influence of the enzymatic hydrolysis of phytate complexes on
starch availability during the alcoholic fermentation process using high gravity
(HG) maize mashes was analyzed. Indicators of the alcoholic fermentation as well
as the fermentation activity of Saccharomyces cerevisiae D-2 strain were
statistically evaluated. Phytate hydrolysis improved the course of the alcoholic
fermentation of HG maize mashes. The final ethanol concentration in the media
supplemented with phytase applied either before or after the starch hydrolysis
increased by 1.0 and 0.6 % v/v, respectively, as compared to the control
experiments. This increase was correlated with an elevated fermentation yield
that was higher by 5.5 and 2.0 L EtOH/100 kg of starch, respectively. Phytate
hydrolysis resulted also in a statistically significant increase in the initial
concentration of fermenting sugars by 14.9 mg/mL of mash, on average, which was a
consequence of a better availability of starch for enzymatic hydrolysis. The
application of phytase increased the attenuation of HG media fermentation thus
improving the economical aspect of the ethanol fermentation process.
PMID- 25119552
TI - Effect of electroporation on bioconversion of isoflavones and probiotic
properties of parents and subsequent passages of Bifidobacterium longum.
AB - This study aimed to evaluate the effects of electroporation on growth,
bioconversion of isoflavones, and probiotic properties of parent organisms and
subsequent passages of Bifidobacterium longum FTDC 8643. Electroporation with the
strength of electric field at 7.5 kV cm(-1) for 3.5 ms was applied on B. longum
FTDC 8643. The viability of B. longum FTDC 8643 increased significantly upon
treatment with electroporation. Such treatment also enhanced the intracellular
and extracellular beta-glucosidase activity, leading to enhanced production of
bioactive isoflavone aglycones in mannitol-soymilk (P < 0.05). In addition, these
treated cells also exhibited better tolerance toward acidic (pH 2 and pH 3) and
intestinal bile salt condition compared to the control (P < 0.05). The
electroporated cell also possessed better adhesion ability and antimicrobial
activity (P < 0.05). However, all these positive effects were only prevalent in
the parent cells and were not observed in their subsequent passages of
electroporated cells. Our results suggested that electroporation could enhance
the bioactive and probiotic potentials of parent cells of B. longum FTDC 8643 and
could be used in the production of probiotic foods with enhanced bioactivity.
PMID- 25119553
TI - Targeting improvements in patient safety at a large academic center: an
institutional handoff curriculum for graduate medical education.
AB - PROBLEM: Handoffs are an integral component of patient care, and the number of
handoffs has increased as a result of duty hours restrictions for resident
physicians. A structured handoff curriculum improves accuracy and has been shown
to decrease medical errors. A standardized approach across all specialties is
lacking in the published literature. The authors discuss the development and
implementation of an institution-wide handoff curriculum for incoming first-year
residents. APPROACH: An Innovation in Graduate Medical Education committee,
including faculty from multiple specialties, identified an educational deficiency
in handoffs and selected this as the target for the educational innovation.
Meetings were held to develop and implement an extensive handoff curriculum for
incoming first-year residents. The designed curriculum included large- and small
group sessions, and a specialty-specific observed simulated handoff experience.
The authors analyzed participants' pre- and postsurveys using descriptive
statistics. OUTCOMES: One hundred and twenty-four participants attended the
formalized handoff training day. Following training, residents recognized that
dedicated time for verbal exchange, templates for accessing and recording
information, interactive handoffs giving priority to ill patients, and
highlighting action items were most important for effective handoff. NEXT STEPS:
Both undergraduate and graduate medical education curricula need to develop
formalized training and methods to assess competencies in handoffs. Training
incoming residents is a logical starting place, but programs should be
systematically disseminated across all specialties, from residents to faculty, in
order to be effectively integrated into the culture of an institution.
PMID- 25119554
TI - Time well spent: the association between time and effort allocation and intent to
leave among clinical faculty.
AB - PURPOSE: To explore the relationship between clinical faculty members'
time/effort in four mission areas, their assessment of the distribution of that
time/effort, and their intent to leave the institution and academic medicine.
METHOD: Faculty from 14 U.S. medical schools participated in the 2011-2012
Faculty Forward Engagement Survey. The authors conducted multivariate logistic
regression analyses to evaluate relationships between clinical faculty members'
self-reported time/effort in each mission area, assessment of time/effort, and
intent to leave the institution and academic medicine. RESULTS: Of the 13,722
clinical faculty surveyed, 8,349 (60.8%) responded. Respondents reported an
average of 54.5% time/effort in patient care. The authors found no relationship
between time/effort in patient care and intent to leave one's institution.
Respondents who described spending "far too much/too much" time in patient care
were more likely to report intent to leave their institution (odds ratio 2.12,
P<.001). Those who assessed their time/effort in all mission areas as "about
right" were less likely to report intent to leave their institution (64/1,135;
5.6%) than those who reported "far too little/too little" or "far too much/too
much" time/effort in one or more mission areas (535/3,671; 14.6%; P<.001).
CONCLUSIONS: Although the authors found no relationship between reported
time/effort in patient care and intent to leave, the perception of "far too
much/too much" time/effort spent in that mission area was correlated with intent
to leave the institution. Efforts to align time/effort spent in each mission area
with faculty expectations may improve retention.
PMID- 25119555
TI - The Quality Improvement Knowledge Application Tool Revised (QIKAT-R).
AB - PURPOSE: Quality improvement (QI) has been part of medical education for over a
decade. Assessment of QI learning remains challenging. The Quality Improvement
Knowledge Application Tool (QIKAT), developed a decade ago, is widely used
despite its subjective nature and inconsistent reliability. From 2009 to 2012,
the authors developed and assessed the validation of a revised QIKAT, the "QIKAT
R." METHOD: Phase 1: Using an iterative, consensus-building process, a national
group of QI educators developed a scoring rubric with defined language and
elements. Phase 2: Five scorers pilot tested the QIKAT-R to assess validity and
inter- and intrarater reliability using responses to four scenarios, each with
three different levels of response quality: "excellent," "fair," and "poor."
Phase 3: Eighteen scorers from three countries used the QIKAT-R to assess the
same sets of student responses. RESULTS: Phase 1: The QI educators developed a
nine-point scale that uses dichotomous answers (yes/no) for each of three QIKAT-R
subsections: Aim, Measure, and Change. Phase 2: The QIKAT-R showed strong
discrimination between "poor" and "excellent" responses, and the intra- and
interrater reliability were strong. Phase 3: The discriminative validity of the
instrument remained strong between excellent and poor responses. The intraclass
correlation was 0.66 for the total nine-point scale. CONCLUSIONS: The QIKAT-R is
a user-friendly instrument that maintains the content and construct validity of
the original QIKAT but provides greatly improved interrater reliability. The
clarity within the key subsections aligns the assessment closely with QI
knowledge application for students and residents.
PMID- 25119556
TI - Gelatinases and extracellular matrix metalloproteinase inducer are associated
with cyclosporin-A-induced attenuation of periodontal degradation in rats.
AB - BACKGROUND: The present study aims to examine the inhibitory effect of
cyclosporin-A (CsA) on periodontal breakdown and to further explore the
correlations of CsA-induced attenuation of periodontal bone loss with the
expressions of gelatinases (i.e., matrix metalloproteinase [MMP]-2 and MMP-9) and
extracellular matrix metalloproteinase inducer (EMMPRIN). METHODS: Forty Sprague
Dawley rats were randomly divided into four groups: 1) control; 2) CsA; 3)
ligature (Lig); and 4) ligature plus CsA (Lig + CsA). The CsA group received 10
mg ? Kg(-1) ? d(-1) CsA for 8 days. The Lig group received silk ligature on
selected molars. The Lig + CsA group received silk ligature and CsA treatment.
The inhibitory effects of CsA on the ligature-induced periodontal breakdown was
examined with microcomputed tomography (micro-CT) and histometric analyses to
analyze the amount of attachment loss, crestal bone loss, connective tissue
attachment, and the surface area with inflammatory cell infiltration. The effects
of CsA on ligature-induced expressions of gelatinases and EMMPRIN in gingival
tissues were examined with Western blotting and zymography, respectively.
RESULTS: By micro-CT and histology, the Lig + CsA group had significantly more
periodontal breakdown than the control and CsA groups but less periodontal
breakdown than the Lig group. Consistent results were found for the expressions
of gelatinases and EMMPRIN among the groups demonstrating that the Lig + CsA
group had significantly less gingival protein expression of gelatinases and
EMMPRIN than the Lig group. CONCLUSIONS: CsA inhibited the expressions of
gelatinase MMPs and EMMPRIN and partially prevented the periodontal breakdown in
ligature-induced experimental periodontitis. The CsA-induced attenuation of
periodontal bone loss was strongly correlated positively with the expressions of
MMP-2, MMP-9, and EMMPRIN in gingiva.
PMID- 25119557
TI - Resistance to cigarette smoke is increased in periodontal ligament cells by
attachment to collagen and fibronectin.
AB - BACKGROUND: The toxic effects of cigarette smoke often presents in smokers as
increased incidence and severity of periodontal disease. These patients
demonstrate symptomatic inflammation, increased probing depth, and tooth loss
likely attributable to the direct effects of cigarette smoke on periodontal
ligament (PDL) fibroblasts. The goal of this in vitro study is to investigate the
direct effects of smoking on PDL fibroblasts, focusing on cell-extracellular
matrix (ECM) interactions and cell survival. METHODS: PDL cells were plated for
various times on tissue culture plastic, PDL-derived ECMs, collagen Type I, or
fibronectin. Cells were exposed to various concentrations of cigarette smoke
extract (CSE) at different times during the cell attachment process.
Subsequently, cell survival was quantified using calcein-acetoxymethyl ester
compound and a fluorescent plate reader. RESULTS: After exposure to CSE, PDL cell
survival increased with increased cell attachment time to plastic. These
observations were independent of soluble factors present in PDL cell-conditioned
media. PDL-derived ECMs and collagen Type I-pretreated plates promoted increased
cell survival after 1 day of cell attachment. Fibronectin-pretreated plates
demonstrated increased cell survival after 3 days of cell attachment.
CONCLUSIONS: Cell-ECM interactions increase survival of PDL cells exposed to CSE.
It is suggested that the increased survival is attributable to PDL cells altering
their ECM, potentially by depositing collagen and fibronectin. This may imply
that cells embedded in an ECM would be more resistant to the toxic effects of
cigarette smoke, leading to increased cell death near the exposed edges of a
wound.
PMID- 25119558
TI - Association of CCL5 and CCR5 gene polymorphisms with periodontitis in Taiwanese.
AB - BACKGROUND: It has been suggested that genetic factors may predispose individuals
to periodontal diseases. The present case-control study aims to test whether the
403 single nucleotide polymorphism of chemokine ligand 5 (CCL5-403) and the 32-bp
deletion of CCR5 (CCR5Delta32) polymorphisms are associated with susceptibility
to chronic and aggressive periodontitis. METHODS: Taiwanese participants (N =
213) were grouped into control group (CG), generalized aggressive periodontitis
(GAgP), or chronic periodontitis (CP) groups. DNA samples were obtained from
peripheral blood. CCL5-403, evaluated by polymerase chain reaction-restriction
fragment length polymorphism, and CCR5Delta32, evaluated by polymerase chain
reaction, were compared among the three groups. RESULTS: There was a significant
association between type of periodontitis and having allele A or G in the CCL5
403 polymorphism. GAgP patients were 3.7 times more likely than CP patients and
2.0 times more likely than CG patients to have allele A, instead of allele G, in
CCL5-403. GAgP patients were 3.1 times more likely than CG patients to have AG
versus GG genotype. GAgP patients were also 5.0 and 19.8 times more likely than
CP patients to have AG and AA genotypes, respectively, compared to GG. For the
CCR5Delta32 polymorphism, no association was found between the type of
periodontitis and having different genotype or allele distributions among GAgP,
CP, or CG patients. CONCLUSION: The single nucleotide polymorphism of CCL5-403 G
substitution by A may play a role in AgP; however, the CCR5Delta32 polymorphism
may not.
PMID- 25119559
TI - Factors affecting utilization of dental services during pregnancy.
AB - BACKGROUND: The aim of this study is to identify and evaluate factors affecting
utilization of dental services during pregnancy. METHODS: Participants in this
cross-sectional study were mothers visiting a community health center for their
infants'/toddlers' immunization. Data were collected through a questionnaire
about demographics, oral health knowledge, attitude, and practices, as well as
barriers to dental visits during pregnancy. Mean (SD) and frequencies were used
for data description. Different factors were analyzed as predictors for
utilization of dental services using multiple logistic regression analysis.
RESULTS: In total, 423 mothers completed the study. Mean (SD) age at delivery was
29.5 (5.3) years. Almost all participants brushed their teeth at least once daily
with toothpaste. During pregnancy, 19.2% of mothers reported difficulties with
brushing, and 25% had dental/periodontal problems. Half of the participants had a
dental visit during pregnancy; 93% were for dental checkups, 80.5% received
preventive care, and 28.8% received dental/periodontal treatments. Canadian-born
women were 48% more likely to visit the dentist during pregnancy compared with
non-Canadian counterparts (P = 0.048). Level of education, dental insurance, and
household income were also positively associated with usage (P <0.001). Mothers
with more knowledge about possible connections between oral health and pregnancy
and those who visited the dentist every 6 months had better odds of visiting the
dentist during pregnancy (P <0.001). CONCLUSION: Three major factors predicting
the utilization of dental services during pregnancy were: 1) perceived need, 2)
habit of regular dental visits, and 3) access to dental services.
PMID- 25119560
TI - Periodontal disease as a risk indicator for poor physical fitness: a cross
sectional observational study.
AB - BACKGROUND: Physical inactivity has been associated with poor oral health. The
aim of this study is to assess whether periodontal disease is a risk indicator
for poor physical fitness. METHODS: This cross-sectional study included 111 males
who performed a physical fitness test (PFT) composed of four exercises: 1) push
ups conducted by pushing the body up and lowering it down using the arms; 2) pull
ups with the body suspended by the arms gripped on a bar; 3) sit-ups in which the
upper and lower vertebrae are lifted from the floor; and 4) running for 12
minutes. A PFT score (range of 1 to 300) was determined for each participant,
with higher scores indicating better physical fitness. One periodontist assessed
attachment loss (AL) and probing depth (PD). Physical fitness was dichotomized
according to whether the highest PFT score was "achieved" or "not achieved."
Multivariable logistic models were fitted adjusting for age, overweight (body
mass index of 25 to 29.9 kg/m(2)), and frequency of daily exercise. RESULTS: The
mean age of the sample was 34.8 +/- 10.3 years. Overweight individuals
demonstrated significantly lower PFT scores (276.9 +/- 24.1 points) than normal
weight individuals (289.3 +/- 16.8 points). Individuals presenting at least one
tooth with AL >= 4 mm had significantly lower PFT scores (277.8 +/- 23.6 points)
compared with those without this status (285.9 +/- 20.2 points). A 1-mm increment
in PD or AL significantly decreased the chance of reaching the highest PFT score
by 69% or 75%, respectively. CONCLUSION: Periodontal disease may be considered a
risk indicator for poor physical fitness in males.
PMID- 25119561
TI - Effects of scaling and root planing on clinical response and serum levels of
adipocytokines in patients with obesity and chronic periodontitis.
AB - BACKGROUND: Despite several investigations suggesting that obesity is a risk
indicator for periodontitis, little is known about the effect of obesity on
periodontal treatment response. The aim of this study is to evaluate the effects
of scaling and root planing (SRP) on clinical parameters and circulating levels
of leptin and adiponectin in patients with obesity with chronic periodontitis
(CP). METHODS: Twenty-four patients with obesity and CP and 24 patients without
obesity with CP were submitted to SRP. Clinical parameters were assessed at
baseline and 3 and 6 months after therapy. Serum levels of leptin and adiponectin
were evaluated at all time points, using enzyme-linked immunosorbent assay.
RESULTS: SRP improved the clinical parameters of both groups at 3 and 6 months (P
< 0.05). Nonetheless, the patients without obesity presented a lower mean probing
depth (PD) at 6 months after therapy and a greater reduction in PD from baseline
to 6 months in the full-mouth analysis (primary outcome variable) and in
initially deep sites (P < 0.05). Leptin serum levels were higher in patients with
obesity than in patients without obesity at all time points (P < 0.05). No
changes in the serum levels of leptin and adiponectin were observed in groups
with and without obesity after therapy (P > 0.05). CONCLUSIONS: Patients with
obesity and CP presented lower reductions in PD than patients without obesity
with CP at 6 months after SRP. Furthermore, the treatment did not affect the
circulating levels of leptin and adiponectin in any group.
PMID- 25119562
TI - The future of stem cell therapy in hernia and abdominal wall repair.
AB - INTRODUCTION: Stem cell therapies have been proposed in preclinical trials as new
treatment options in abdominal wall repair. MATERIALS AND METHODS: This work
lists sources of feasible cell lines and the current status of literature and
provides a cautious outlook into future developments. Special attention was paid
to translational issues and practicabilty in a complex field. CONCLUSION: Cell
based therapies will play a role in the clinical setting in the future.
Regulatory and ethical issues need to be addressed as well as the proof of cost
effectiveness.
PMID- 25119563
TI - Long-term outcome after randomizing prolene hernia system, mesh plug repair and
Lichtenstein for inguinal hernia repair.
AB - PURPOSE: To assess long-term superiority in terms of chronic pain between prolene
hernia system (PHS), mesh plug repair (MPR) and Lichtenstein (L) technique for
inguinal hernia repair. METHODS: Eight years after randomizing three commonly
used techniques for primary inguinal hernia repair, the outcome was evaluated
with a questionnaire measuring pain on verbal descriptor and visual analogue
scales, including limitations on daily life activities, sensory disturbances and
recurrences. From previous results patients characteristics, operative details
and short- and mid-term pain outcome were extracted. RESULTS: 270 out of 308
eligible patients (88%) completed the follow-up after median 7.6 years (range 6.9
9.2) after the inguinal hernia operation. No significant differences between the
repair techniques were found for pain, sensory disturbances or recurrences.
Overall, the hernia recurrence rate was 6.3%. In total 63 patients (23%) reported
long-term pain of which one-fourth graded this moderate to severe. Pain was
experienced at least weekly by 26 patients (10%) and limiting daily activities
for 36 patients (13%). With regard to the previously reported pain at 3 and 15
months follow-up, 106 patients (39%) experience no pain at all. For 101 patients
(37%), initial pain disappeared. 41 patients (15%) suffered persisting pain at
all three measure moments. 22 patients (8%) reported pain at 8 years follow-up
after an initial pain-free period. CONCLUSIONS: Long-term outcome after
randomizing PHS, MPR and L showed no clinically relevant differences in chronic
pain and its consequences. Although chronic pain is diminishing over time it
remains a serious complication and has sometimes an onset long after the inguinal
repair.
PMID- 25119566
TI - Impact of supplementary feeding on reproductive success of white storks.
AB - European white stork (Ciconia ciconia) populations have been object to several
conservation measures such as reintroduction programs, habitat improvement or
supplementary feeding in the last decades. Although recent white stork censuses
revealed an upward trend of most of the western populations, evaluations of the
relative importance of certain conservation measures are still scarce or even
lacking. In our study we analyzed the effect of supplementary feeding on the
reproductive success of white storks in conjunction with other factors such as
weather or nest site characteristics. We present data of 569 breeding events at
80 different nest sites located in variable distances to an artificial feeding
site at Affenberg Salem (south-western Germany) collected from 1990-2012. A
multilevel Poisson regression revealed that in our study population (1)
reproductive success was negatively affected by monthly precipitation in April,
May and June, (2) pairs breeding on power poles had a lower reproductive success
than pairs breeding on platforms or trees and (3) reproductive success was
significantly higher in pairs breeding in close distance to the feeding site. The
number of fledglings per nest decreased by 8% per kilometer distance to the
feeding site. Our data suggest that supplementary feeding increases fledgling
populations which may be a tool to attenuate population losses caused by factors
such as habitat deterioration or unfavorable conditions in wintering habitats.
PMID- 25119564
TI - Foodborne cereulide causes beta-cell dysfunction and apoptosis.
AB - AIMS/HYPOTHESIS: To study the effects of cereulide, a food toxin often found at
low concentrations in take-away meals, on beta-cell survival and function.
METHODS: Cell death was quantified by Hoechst/Propidium Iodide in mouse (MIN6)
and rat (INS-1E) beta-cell lines, whole mouse islets and control cell lines
(HepG2 and COS-1). Beta-cell function was studied by glucose-stimulated insulin
secretion (GSIS). Mechanisms of toxicity were evaluated in MIN6 cells by mRNA
profiling, electron microscopy and mitochondrial function tests. RESULTS: 24 h
exposure to 5 ng/ml cereulide rendered almost all MIN6, INS-1E and pancreatic
islets apoptotic, whereas cell death did not increase in the control cell lines.
In MIN6 cells and murine islets, GSIS capacity was lost following 24 h exposure
to 0.5 ng/ml cereulide (P<0.05). Cereulide exposure induced markers of
mitochondrial stress including Puma (p53 up-regulated modulator of apoptosis,
P<0.05) and general pro-apoptotic signals as Chop (CCAAT/-enhancer-binding
protein homologous protein). Mitochondria appeared swollen upon transmission
electron microscopy, basal respiration rate was reduced by 52% (P<0.05) and
reactive oxygen species increased by more than twofold (P<0.05) following 24 h
exposure to 0.25 and 0.50 ng/ml cereulide, respectively.
CONCLUSIONS/INTERPRETATION: Cereulide causes apoptotic beta-cell death at low
concentrations and impairs beta-cell function at even lower concentrations, with
mitochondrial dysfunction underlying these defects. Thus, exposure to cereulide
even at concentrations too low to cause systemic effects appears deleterious to
the beta-cell.
PMID- 25119565
TI - Reduced functional reserve in patients with age-related white matter changes: a
preliminary FMRI study of working memory.
AB - Subcortical age-related white matter changes (ARWMC) are a frequent finding in
healthy elderly people suggested to cause secondary tissue changes and possibly
affecting cognitive processes. We aimed to determine the influence of the extent
of ARWMC load on attention and working memory processes in healthy elderly
individuals. Fourteen healthy elderly subjects (MMSE >26; age 55-80 years)
performed three fMRI tasks with increasing difficulty assessing alertness,
attention (0-back), and working memory (2-back). We compared activation patterns
in those with only minimal ARWMC (Fazekas 0-1) to those with moderate to severe
ARWMC (Fazekas 2-3). During the fMRI experiments, the study population showed
activation in brain areas typically involved in attention and working memory with
a recruitment of cortical areas with increasing task difficulty. Subjects with
higher lesion load showed a higher activation at all task levels with only sparse
increase of signal with increasing complexity. In the lower lesion load group,
rising task difficulty lead to a significant and widely distributed increase of
activation. Although the number of patients included in the study is small, these
findings suggest that even clinically silent ARWMC may affect cognitive
processing and lead to compensatory activation during cognitive tasks. This can
be interpreted as a reduction of functional reserve and may pose a risk for
cognitive decline in these patients.
PMID- 25119567
TI - Hydroclimate variations in central and monsoonal Asia over the past 700 years.
AB - Hydroclimate variations since 1300 in central and monsoonal Asia and their
interplay on interannual and interdecadal timescales are investigated using the
tree-ring based Palmer Drought Severity Index (PDSI) reconstructions. Both the
interannual and interdecadal variations in both regions are closely to the
Pacific Decadal Oscillation (PDO). On interannual timescale, the most robust
correlations are observed between PDO and hydroclimate in central Asia.
Interannual hydroclimate variations in central Asia are more significant during
the warm periods with high solar irradiance, which is likely due to the enhanced
variability of the eastern tropical Pacific Ocean, the high-frequency component
of PDO, during the warm periods. We observe that the periods with significant
interdecadal hydroclimate changes in central Asia often correspond to periods
without significant interdecadal variability in monsoonal Asia, particularly
before the 19th century. The PDO-hydroclimate relationships appear to be bridged
by the atmospheric circulation between central North Pacific Ocean and Tibetan
Plateau, a key area of PDO. While, in some periods the atmospheric circulation
between central North Pacific Ocean and monsoonal Asia may lead to significant
interdecadal hydroclimate variations in monsoonal Asia.
PMID- 25119569
TI - [Germ cell and embryonal tumors].
AB - Germ cell tumors, which constitute approximately 3-5% of tumors of the central
nervous system (CNS), can be subdivided into germinomas, embryonal carcinomas,
yolk sac tumors, choriocarcinomas, teratomas and mixed germ cell tumors. The
diagnosis of intracranial germ cell tumor is based on the clinical symptoms,
detection of tumor markers, such as alpha fetoprotein (AFP) and the beta subunit
of human chorionic gonadotropin (beta-hCG) in blood and cerebrospinal fluid
(CSF), magnetic resonance imaging (MRI) of the brain and spinal cord, CSF
cytology and histology. The diagnosis of a secreting germ cell tumor, i.e. a non
germinoma, can be made by the determination of AFP and hCG as tumor markers.
Germinomas are radiosensitive but are equally as sensitive to chemotherapy.
Teratomas of the CNS are mostly diagnosed in newborns and infants. The most
decisive role in the treatment of teratomas is played by as complete a resection
as possible. Chemotherapy and irradiation play a subordinate role.Embryonal
tumors, which constitute approximately 15-20% of CNS tumors, include
medulloblastomas, primitive neuroectodermal tumors (PNET) of the CNS and the
atypical teratoid rhabdoid tumor of the CNS. Medulloblastoma is the most common
malignant brain tumor in childhood and adolescence. The incidence peak is the
fifth year of life with a male predisposition in a ratio of 1.5:1.
Medulloblastomas constitute 12-25% of all pediatric CNS tumors and 30-40% of
pediatric tumors of the posterior cranial fossa. At the time of diagnosis
evidence of dissemination in the CSF cavity is found in approximately 40% of
patients. The extreme cell density makes medulloblastomas hyperdense in computed
tomography (CT) and can therefore be differentiated from hypodense astrocytomas.
The PNETs are histologically related to medulloblastomas, pineoblastomas,
atypical teratoid rhabdoid tumors and peripheral neuroblastomas. They are
relatively rare in children constituting less than 5% of supratentorial
neoplasms. Patients are mostly clinically conspicuous due to macrocephalus and
signs of brain pressure and/or seizures. In native CT the solid components of
PNETs show a hyperdensity compared to the surrounding brain parenchyma probably
due to the high cell density. Cysts and calcification are often detectable. The
survival rate of children with CNS tumors has continuously increased in recent
years. When corresponding clinical symptoms appear, such as headache, nausea or
vomiting when fasting, all of which are evidence of increased intracranial
pressure, MRI should be carried out as quickly as possible. Children should be
treated in centers with departments of pediatric oncology and hematology and
within the framework of studies.
PMID- 25119568
TI - Host density and competency determine the effects of host diversity on trematode
parasite infection.
AB - Variation in host species composition can dramatically alter parasite
transmission in natural communities. Whether diverse host communities dilute or
amplify parasite transmission is thought to depend critically on species traits,
particularly on how hosts affect each other's densities, and their relative
competency as hosts. Here we studied a community of potential hosts and/or decoys
(i.e. non-competent hosts) for two trematode parasite species, Echinostoma
trivolvis and Ribeiroia ondatrae, which commonly infect wildlife across North
America. We manipulated the density of a focal host (green frog tadpoles, Rana
clamitans), in concert with manipulating the diversity of alternative species, to
simulate communities where alternative species either (1) replace the focal host
species so that the total number of individuals remains constant (substitution)
or (2) add to total host density (addition). For E. trivolvis, we found that
total parasite transmission remained roughly equal (or perhaps decreased
slightly) when alternative species replaced focal host individuals, but parasite
transmission was higher when alternative species were added to a community
without replacing focal host individuals. Given the alternative species were
roughly equal in competency, these results are consistent with current theory.
Remarkably, both total tadpole and per-capita tadpole infection intensity by E.
trivolvis increased with increasing intraspecific host density. For R. ondatrae,
alternative species did not function as effective decoys or hosts for parasite
infective stages, and the diversity and density treatments did not produce clear
changes in parasite transmission, although high tank to tank variation in R.
ondatrae infection could have obscured patterns.
PMID- 25119570
TI - [Soft tissue tumors : Imaging strategy for local primary diagnostics -
manifestation, pearls and pitfalls in MRI].
AB - Only approximately 1% of soft tissue tumors are malignant. Potentially malignant
lesions can be recognized by ultrasound and submitted for magnetic resonance
imaging (MRI). Radiography can supply valuable additional information. The MRI
examination is the imaging reference standard for soft tissue tumors and also
serves as local staging modality. Lesions which are indeterminate in MRI, or in
which therapy is dependent on histology results, should be biopsied. Referral to
a reference center is recommended. The multitude of soft tissue tumor entities
are classified according to the World Health Organization (WHO) system (latest
version 2013). Some tumors show characteristic locations and MRI morphology.
Sarcoma staging by imaging is influenced by the size and site in comparison to
the surface fascia. International standards must be adhered to: decisive for the
patient is in particular the care by an experienced interdisciplinary tumor team.
PMID- 25119571
TI - A preliminary pilot randomized crossover study of uzara (Xysmalobium undulatum)
versus ibuprofen in the treatment of primary dysmenorrhea.
AB - OBJECTIVE: Preliminary evaluation of efficacy and safety of uzara use in
treatment of moderate and severe primary dysmenorrhea in comparison to ibuprofen.
MATERIALS AND METHODS: This randomized, comparative two way cross-over study
comprised 60 single female students at Faculty of Medicine, Ain Shams University,
Egypt, aged 19-28 years with moderate (n = 46) or severe (n = 14) primary
dysmenorrhea. Participants were randomized to take either uzara (80 mg/8 hours
for two doses, then 40 mg/8 hours) then ibuprofen (400 mg/6 hours) in two
subsequent cycles or vice versa. The pain intensity, using VAS, was recorded
immediately before taking the medication (0 hour) and after 4, 12, 24, 48-60, 96
120 hours. Main outcome measures included effectiveness of pain relief defined as
drop of VAS to 3 or less, patient's global evaluation of the drug, absence from
school, the use of a rescue medication, and, in those who continued the
treatment, the pain intensity difference (PID) at different points after start of
medication and its sum (SPID). RESULTS: Uzara was comparably effective to
ibuprofen (78.3% vs. 86.7% of cycles; respectively), with comparable rates of
effectiveness on global evaluation (being around 50% for either drug), and rates
of school absences (11.7% vs. 13.3%; respectively). The need for rescue
medication was different (18.3% and 10%; respectively), albeit with no
statistical significance. The means of PID at different time points and SPID were
comparable, with significantly lower average mean of VAS scores compared to that
felt with no medication (1.6 vs. 6.8, p<0.001). Side effects were less with uzara
than ibuprofen (0% vs. 8.3%, p<0.05). CONCLUSIONS: Uzara might be as effective as
ibuprofen in management of primary dysmenorrhea but with less side effects. These
findings need to be confirmed by a properly designed trial with a larger sample
size. TRIAL REGISTRATION: Current Controlled Trials ISRCTN25618258.
PMID- 25119574
TI - Adjunctive treatments in pediatric acute respiratory distress syndrome.
AB - Acute respiratory distress syndrome (ARDS) is a devastating process that involves
pulmonary inflammation, alveolar damage and hypoxemic respiratory failure.
Although advances in management approaches over the past two decades have
resulted in significantly improved outcomes, death from pediatric ARDS may still
occur in up to 35% of patients. While invasive mechanical ventilation is an
essential component of ARDS management, various adjuncts have been utilized as
treatment for these patients. However, evidence-based data in infants and
children in this area are lacking. In this article, the authors review the
available evidence supporting (or not supporting) the use of non-ventilatory
adjunctive strategies in the management of pediatric ARDS, including prone
positioning, pulmonary vasodilators, beta-agonists, steroids and surfactant.
PMID- 25119573
TI - Dysfunction of bone marrow vascular niche in acute graft-versus-host disease
after MHC-haploidentical bone marrow transplantation.
AB - Acute graft-versus-host disease (aGvHD) is the most common complication of
allogeneic hematopoietic stem cell transplantation (HSCT), which is often
accompanied by impaired hematopoietic reconstitution. Sinusoidal endothelial
cells (SECs) constitute bone marrow (BM) vascular niche that plays an important
role in supporting self-renewal capacity and maintaining the stability of HSC
pool. Here we provide evidences that vascular niche is a target of aGvHD in a
major histocompatibility complex (MHC)-haploidentical matched murine HSCT model.
The results demonstrated that hematopoietic cells derived from GvHD mice had the
capacity to reconstitute hematopoiesis in healthy recipient mice. However,
hematopoietic cells from healthy donor mice failed to reconstitute hematopoiesis
in GvHD recipient mice, indicating that the BM niche was impaired by aGvHD in
this model. We further demonstrated that SECs were markedly reduced in the BM of
aGvHD mice. High level of Fas and caspase-3 expression and high rate of apoptosis
were identified in SECs, indicating that SECs were destroyed by aGvHD in this
murine HSCT model. Furthermore, high Fas ligand expression on engrafted donor
CD4(+), but not CD8(+) T cells, and high level MHC-II but not MHC-I expression on
SECs, suggested that SECs apoptosis was mediated by CD4(+) donor T cells through
the Fas/FasL pathway.
PMID- 25119572
TI - Tumour cells expressing single VEGF isoforms display distinct growth, survival
and migration characteristics.
AB - Vascular endothelial growth factor-A (VEGF) is produced by most cancer cells as
multiple isoforms, which display distinct biological activities. VEGF plays an
undisputed role in tumour growth, vascularisation and metastasis; nevertheless
the functions of individual isoforms in these processes remain poorly understood.
We investigated the effects of three main murine isoforms (VEGF188, 164 and 120)
on tumour cell behaviour, using a panel of fibrosarcoma cells we developed that
express them individually under endogenous promoter control. Fibrosarcomas
expressing only VEGF188 (fs188) or wild type controls (fswt) were typically
mesenchymal, formed ruffles and displayed strong matrix-binding activity. VEGF164
and VEGF120-producing cells (fs164 and fs120 respectively) were less typically
mesenchymal, lacked ruffles but formed abundant cell-cell contacts. On 3D
collagen, fs188 cells remained mesenchymal while fs164 and fs120 cells adopted
rounded/amoeboid and a mix of rounded and elongated morphologies respectively.
Consistent with their mesenchymal characteristics, fs188 cells migrated
significantly faster than fs164 or fs120 cells on 2D surfaces while contractility
inhibitors accelerated fs164 and fs120 cell migration. VEGF164/VEGF120 expression
correlated with faster proliferation rates and lower levels of spontaneous
apoptosis than VEGF188 expression. Nevertheless, VEGF188 was associated with
constitutively active/phosphorylated AKT, ERK1/2 and Stat3 proteins. Differences
in proliferation rates and apoptosis could be explained by defective signalling
downstream of pAKT to FOXO and GSK3 in fs188 and fswt cells, which also
correlated with p27/p21 cyclin-dependent kinase inhibitor over-expression. All
cells expressed tyrosine kinase VEGF receptors, but these were not
active/activatable suggesting that inherent differences between the cell lines
are governed by endogenous VEGF isoform expression through complex interactions
that are independent of tyrosine kinase receptor activation. VEGF isoforms are
emerging as potential biomarkers for anti-VEGF therapies. Our results reveal
novel roles of individual isoforms associated with cancer growth and metastasis
and highlight the importance of understanding their diverse actions.
PMID- 25119576
TI - [(Gastro-)intestinal tract (reflections to issue 4/2014 - editorial)].
PMID- 25119575
TI - [Nerve-preserving low anterior rectum resection].
AB - AIM: The Performance of an oncological low anterior rectum resection with
preservation of the sympathic and parasympathic nerves is illustrated.
INDICATION: The total mesorectal excision (TME) by Robert Heald et al. is the
gold standard for rectal cancer operations which has lowered drastically the
local recurrence rate. As the survival data improve, the new focus is the
postoperative quality of life with preserving of the bladder and sexual function.
METHOD: We demonstrate an anterior rectal cancer operation with preserving of the
sympathetic and parasympathetic nerves step by step. CONCLUSION: The critical
parts of preserving the nerves with the N. hypogastricus superior and inferior as
well as the neurovascular bundle "erigent pillar" are demonstrated.
PMID- 25119577
TI - [Barrett's neoplasia: where is the problem?].
AB - The Barrett mucosa is characterised by metaplastic transformation in the distal
oesophagus from squamous epithelium into columnar-lined cells and shows an
increased risk for progression into adenocarcinoma. Up to date an international
definition of Barrett's oesophagus is still lacking and it is also difficult to
separate low-grade dysplasia/intraepithelial neoplasia from high-grade
dysplasia/intraepithelial neoplasia. The present review describes the criteria
for the histological diagnosis, discusses the possibilities of endoscopic
diagnosis and highlights the biomarkers of the Barrett mucosa.
PMID- 25119578
TI - [Helicobacter pylori: short overview on selected data from the history and their
value for clinical medicine, in particular, surgery - what does the
(general/abdominal) surgeon need to know].
AB - The discovery of Helicobacter pylori (H. pylori) represents one of the most
notable events in the field of experimental and clinical medicine with great
impact to daily practice even to surgery. It has led to a paradigm shift in the
treatment of peptic ulcer disease. For the time period of almost one century,
several scientists had described spiral-shaped bacteria in the stomach of animals
and humans. However, it lasted till the early 1980s when Robin Warren and Barry
Marshall successfully cultured H. pylori and recognised its causal relationship
to chronic gastritis and peptic ulcer disease. Since then, our knowledge about H.
pylori and related diseases has been continuously growing. Today, the bacterium
is known to be mainly responsible for the development of chronic gastritis,
peptic ulcer disease, MALT lymphoma and is considered as the main risk factor for
the development of gastric cancer - all this led to a switch in the basic
aetiopathogenetic considerations. In particular, eradication of H. pylori helped
to i) develop an aetiology-based therapeutic and preventive approach to the
diseases listed above according and adapted to findings, stage and manifestation,
and ii) define a new role of surgery in the treatment concept. In addition, more
and more evidence is being gathered for a possible association between the
bacterium and several extragastric diseases.
PMID- 25119580
TI - The placebo effect, sleep difficulty, and side effects: a balanced placebo model.
AB - Medical treatment is usually accompanied by a warning about potential side
effects. While constituting an important component of informed consent, these
warnings may themselves contribute to side effects via the placebo effect. We
tested this possibility using a 2 * 2 between-subjects design. Under the guise of
a trial of a new hypnotic, 91 undergraduates experiencing difficulty sleeping
were allocated to receive a warning about a target side effect (either increase
or decrease in appetite, counterbalanced) or no warning and then to receive
placebo treatment or no treatment for one week. Placebo treatment led to
significantly better sleep on almost all self-reported outcomes, suggesting a
placebo effect for reported sleep difficulty. Actigraphy recordings were
unaffected by treatment. There was a clear effect of the warning in that placebo
treated participants who were warned about side effects were much more likely to
report the target side effect than those not warned about side effects.
Implications for clinical practice are discussed.
PMID- 25119582
TI - Non-invasive whole-body plethysmograph for assessment and prediction of radiation
induced lung injury using simultaneously acquired nitric oxide and lung volume
measurements.
AB - Radiation-induced lung injury (RILI) is a prevalent side effect in patients who
undergo thoracic irradiation as part of their cancer treatment. Preclinical
studies play a major role in understanding disease onset under controlled
experimental conditions. The aim of this work is to develop a single-chambered
optimized, non-invasive, whole-body plethysmograph prototype for unrestrained
small animal lung volume measurements for preclinical RILI studies. The system is
also designed to simultaneously obtain nitric oxide (NO) measurements of the
expired breath. The device prototype was tested using computer simulations,
phantom studies and in vivo measurements in experimental animal models of RILI.
The system was found to improve resemblance to true breathing signal
characteristics as measured by improved skewness (21.83%) and kurtosis (51.94%)
in addition to increased overall signal sensitivity (3.61%) of the acquired
breath signal, when compared to matching control data. NO concentration data was
combined with breath measurements in order to predict early RILI onset. The
system was evaluated using serial weekly measurements in hemi-thorax irradiated
rats (n = 8) yielding a classification performance of 50.0%, 62.5%, 87.5% using
lung volume only, NO only, and combined measurements of both, respectively. Our
results indicate that improved performance could be achieved when measurements of
lung volume are combined with those of NO. This would provide the overall
plethysmography system with the ability to provide useful diagnostic and
prognostic information for preclinical and, potentially, clinical thoracic dose
escalation studies.
PMID- 25119581
TI - Therapeutic strategies for cancer treatment related peripheral neuropathies.
AB - OPINION STATEMENT: Chemotherapy-induced peripheral neuropathy (CIPN) is a common
toxicity associated with multiple chemotherapeutic agents. CIPN may have a
detrimental impact on patients' quality of life and functional ability, as well
as result in chemotherapy dose reductions. Although symptoms of CIPN can improve
with treatment completion, symptoms may persist. Currently, the treatment options
for CIPN are quite limited. Duloxetine, a serotonin-norepinephrine reuptake
inhibitor, has the most evidence supporting its use in the treatment of CIPN.
Other agents with potential benefit for the treatment of established CIPN include
gabapentinoids, venlafaxine, tricyclic antidepressants, and a topical gel
consisting of the combination of amitriptyline, ketamine, and baclofen; none of
these, however, has been proven to be helpful and ongoing/future studies may well
show that they are not beneficial. The use of these agents is often based on
their efficacy in the treatment of non-CIPN neuropathic pain, but this does not
necessarily mean that they will be helpful for CIPN-related symptoms. Other
nonpharmacologic interventions including acupuncture and Scrambler therapy are
supported by positive preliminary data; however, further larger, placebo
controlled trial data are needed to confirm or refute their effectiveness.
PMID- 25119583
TI - Blockade of epidermal growth factor receptor/mammalian target of rapamycin
pathway by Icariside II results in reduced cell proliferation of osteosarcoma
cells.
AB - Icariside II is considered one of the most important natural flavonoids with
multiple bioactivities from traditional Chinese medicine Yin Yanghuo (YYH) or
Horny Goat Weed (Epimedium koreanum Nakai). Previous studies show that Icariside
II exhibits potent cytotoxicity against a broad spectrum of human cancer cells
through various signaling transduction pathways. However, there are few reports
about the effect of Icariside II on osteosarcoma cell. In this study, we found
that Icariside II decreased cell proliferation in human osteosarcoma MG-63 cells
and human osteosarcoma Saos-2 cells. In addition, Icariside II inactivated
EGFR/mTOR signaling pathway, including EGFR, PI3K/AKT/PRAS40, Raf/MEK/ERK as well
as mTOR. Furthermore, Icariside II inhibited epidermal growth factor (EGF)
induced activation of EGFR/mTOR signaling pathway. Pretreatment of EGF partially
reversed cell viability decreased by Icariside II. Importantly, Icariside II
inhibited the proliferation of transplantable tumors and EGFR/mTOR signaling
pathway in sarcoma-180 bearing mice. In summary, these results indicate that
Icariside II inhibits the proliferation of osteosarcoma cells in vitro and in
vivo via EGFR/mTOR signaling pathway.
PMID- 25119585
TI - Antiretroviral therapy adherence measurement in non-clinical settings in South
India.
AB - Optimal adherence to antiretroviral therapy (ART) is key to viral suppression,
but may be impeded by psychosocial consequences of HIV-infection such as stigma
and depression. Measures of adherence in India have been examined in clinic
populations, but little is known about the performance of these measures outside
clinical settings. We conducted a cross-sectional study of 151 Tamil-speaking
people living with HIV/AIDS (PLHA) in India recruited through HIV support
networks and compared single item measures from the Adult AIDS Clinical Trial
Group (AACTG) scale, a visual analog scale (VAS), and a question on timing of
last missed dose. Depression was measured using the Major Depression Inventory
(MDI) and HIV-related stigma was measured using an adaptation of the Berger
Stigma Scale. Mean age was 35.6 years (SD +/- 5.9); 55.6% were male; mean MDI
score was 11.9 (SD +/- 9.1); and mean stigma score was 67.3 (SD +/- 12.0). Self
reported perfect adherence (no missed doses) was 93.3% using the AACTG item,
87.1% using last missed dose, and 83.8% using the VAS. The measures had moderate
agreement with each other (kappa 0.45-0.57). Depression was associated with lower
adherence irrespective of adherence measure used, and remained significantly
associated in multivariable analyses adjusting for age and marital status. Stigma
was not associated with adherence irrespective of the measure used. The VAS
captured the greatest number of potentially non-adherent individuals and may be
useful for identifying PLHA in need of adherence support. Given the consistent
and strong association between poorer adherence and depression, programs that
jointly address adherence and mental health for PLHA in India may be more
effective than programs targeting only one.
PMID- 25119584
TI - A cautionary tale for autologous vascular tissue engineering: impact of human
demographics on the ability of adipose-derived mesenchymal stem cells to recruit
and differentiate into smooth muscle cells.
AB - Autologous tissue-engineered blood vessels (TEBVs) generated using adult stem
cells have shown promising results, but many preclinical evaluations do not test
the efficacy of stem cells from patient populations likely to need therapy (i.e.,
elderly and diabetic humans). Two critical functions of these cells will be (i)
secreting factors that induce the migration of host cells into the graft and (ii)
differentiating into functional vascular cells themselves. The purpose of this
study was to analyze whether adipose-derived mesenchymal stem cells (AD-MSCs)
sourced from diabetic and elderly patients have a reduced ability to promote
human smooth muscle cell (SMC) migration and differentiation potential toward
SMCs, two important processes in stem cell-based tissue engineering of vascular
grafts. SMC monolayers were disrupted in vitro by a scratch wound and were
induced to close the wound by exposure to media conditioned by AD-MSCs from
healthy, elderly, and diabetic patients. Media conditioned by AD-MSCs from
healthy patients promoted the migration of SMCs and did so in a dose-dependent
manner; heating the media to 56 degrees C eliminated the media's potency. AD-MSCs
from diabetic and elderly patients had a decreased ability to differentiate into
SMCs under angiotensin II stimulation; however, only AD-MSCs from elderly donors
were unable to promote SMC migration. Gender and body-mass index of the patients
showed no effect on either critical function of AD-MSCs. In conclusion, AD-MSCs
from elderly patients may not be suitable for autologous TEBVs due to inadequate
promotion of SMC migration and differentiation.
PMID- 25119586
TI - Attachment styles and sexual dysfunctions: a case-control study of female and
male sexuality.
AB - The aim of this study was to investigate attachment styles in a group of women
and men with sexual dysfunction. We recruited 44 subjects (21 women and 23 men)
with sexual dysfunction and 41 subjects (21 women and 20 men) with healthy sexual
function as the control group. Validated instruments for the evaluation of male
and female sexual dysfunctions (M/F SD) and a psychometric tool specifically
designed to investigate attachment style were administered. In women, significant
differences were found between subjects with sexual dysfunction and healthy
controls. The scales indicating an insecure attachment showed: discomfort with
closeness (FSD = 42.85 +/- 11.55 vs CTRL = 37.38 +/- 8.54; P < 0.01),
relationship as secondary (FSD = 26.76 +/- 2.60 vs CTRL = 18.42 +/- 7.99; P <
0.01), and need for approval (FSD=26.38 +/- 3.61 vs CTRL = 20.76 +/- 7.36; P <
0.01). Healthy women also had significantly higher scores in secure attachment
(confidence: FSD = 24.57 +/- 3.89 vs CTRL = 33.42 +/- 5.74; P < 0.01). Men with
sexual dysfunctions differed from healthy men in confidence (MSD = 30 +/- 6.33 vs
CTRL = 36.05 +/- 5.26; P < 0.01) and in discomfort with closeness (MSD = 39.08 +/
8 vs CTRL = 34.25 +/- 7.54; P < 0.05). These results suggest that particular
aspects related to insecure attachment have a determinant role in people with
sexual dysfunctions. It is therefore fundamental to identify the attachment
styles and relational patterns in patients receiving counselling and
psychological treatments focussed on sexual problems.
PMID- 25119588
TI - Strong association of high urinary iodine with thyroid nodule and papillary
thyroid cancer.
AB - This study demonstrates a strong association of high urinary iodine with thyroid
nodules and papillary thyroid cancer as well as aggressive cancer features,
suggesting that high urinary iodine is a risk factor for thyroid cancer. The risk
of high iodine intake for thyroid cancer has been suggested but not established.
The objective of the study was to evaluate the relationship between urine iodine
levels and thyroid nodule and thyroid cancer. We preoperatively tested fasting
urine iodine in 154 thyroid nodule patients and correlated the results with
pathological diagnoses and compared with 306 subjects as normal control. The
median urine iodine (MUI) was 331.33 MUg/L in patients with benign thyroid
nodules versus 466.23 MUg/L in patients with papillary thyroid cancer (PTC)
(P=0.003), both of which were in the excessive iodine state and higher than the
MUI of 174.30 MUg/L in the control group (P < 0.001), which was in the sufficient
iodine state. Excessive iodine state (MUI>300 MUg/L) was seen in 62.75% of
patients with benign thyroid nodules and 66.99% of patients with PTC, both of
which were significantly higher than the iodine excessive rate of 19.93% in the
control group (P<0.001). Moreover, MUI in patients with PTC with lymph node
metastasis was significantly higher than that of PTC patients without lymph node
metastasis (P<0.001). Urine iodine of thyroid cancer patients with stage III and
IV disease was significantly higher than that of patients with stage I and II
diseases (P<0.001). Multivariable analyses showed that, like sand calcification
of thyroid nodule and TSH, urine iodine was an independent risk factor for PTC.
These data demonstrate a significant association between high urinary iodine and
benign and malignant thyroid nodules and PTC aggressiveness, supporting high
urinary iodine as a risk factor for thyroid malignancy. Further studies are
warranted to confirm these findings.
PMID- 25119587
TI - Kruppel-like factor 5 as potential molecular marker in cervical cancer and the
KLF family profile expression.
AB - Cervical cancer (CC) as other cancer types, presents molecular deregulations,
such as the alterations of transcription factors. Kruppel-like factors (KLF) are
a family of transcriptional regulators. They are involved in diverse cellular
processes, such as proliferation, apoptosis, and angiogenesis among others. Here,
we analyzed the expression of all 17 KLF members at messenger RNA (mRNA) level,
and protein expression of the two most commonly altered KLF5 and KLF6 in cervical
tissues. Fifty-nine cervical tissues ranging from normal tissue to CC were
evaluated for KLF1-17 mRNA expression by end-point RT-PCR and KLF5 by qRT-PCR.
For KLF5 and KLF6 protein analysis, a tissue microarray was constructed
containing the 59 cases and subjected for immunohistochemistry assay and KLF6
IVS1-27G>A single nucleotide polymorphism by direct DNA sequencing. KLF2-16
expressions were present in normal tissue, whereas all 17 were present in Low
Grade Squamous Intraepithelial Lesion, High-Grade-SIL and CC, unrelated to
presence of human papillomavirus (HPV). KLF5 mRNA expression gradually increased
throughout the subgroups and overexpressed in CC (p=0.01). KLF5 and KLF6 proteins
were immunodetected in all samples. For the KLF6 SNP analysis, 80% of the CC
population analyzed presented GG genotype and the remaining 20% presented GA
genotype (p=0.491). Our present data show that KLFs expression could not be
related to HPV presence, at least at transcriptional level, and KLF5 mRNA
overexpression could represent a potential molecular marker for CC; KLF6 SNP has
no relation to increased risk of CC.
PMID- 25119589
TI - Association between murine double minute 2 T309G polymorphism and risk of liver
cancer.
AB - During the past decade, a number of studies were published to evaluate the
association between murine double minute 2 (MDM2) T309G polymorphism and risk of
liver cancer. However, the association between MDM2 T309G polymorphism and risk
of liver cancer was still unclear owing to the conflicting results from those
published studies. An undated meta-analysis of all eligible studies was carried
out to comprehensively assess the association. The pooled odds ratio (OR) with 95
% confidence interval (95% CI) was used to evaluate the association between MDM2
T309G polymorphism and risk of liver cancer. Finally, ten studies with a total of
2,243 cases and 3,471 controls were finally included into the meta-analysis.
Overall, there was an association between MDM2 T309G polymorphism and risk of
liver cancer (G vs. T: OR=1.39, 95% CI 1.17-1.64, P<0.001; GG vs. TT: OR=1.87,
95% CI 1.34-2.62, P<0.001; GG/GT vs. TT: OR=1.61, 95 % CI 1.24-2.08, P<0.001).
Subgroup analysis in Europeans showed that there was also an association between
MDM2 T309G polymorphism and risk of liver cancer in Europeans (G vs. T: OR=1.81,
95% CI 1.45-2.27, P<0.001; GG vs. TT: OR=3.26, 95% CI 1.99-5.32, P<0.001; GG/GT
vs. TT: OR=2.20, 95% CI 1.58-3.07, P<0.001). Subgroup analysis in Asians showed
that there was also an association between MDM2 T309G polymorphism and risk of
liver cancer in Asians (G vs. T: OR=1.27, 95% CI 1.06-1.52, P=0.010; GG vs. TT:
OR=1.59, 95% CI 1.11-2.27, P=0.011; GG/GT vs. TT: OR=1.41, 95% CI 1.07-1.87,
P=0.016). The meta-analysis provides a strong evidence for the association
between MDM2 T309G polymorphism and risk of liver cancer.
PMID- 25119590
TI - Molecular regulation of ovarian cancer cell invasion.
AB - The molecular mechanism underlying ovarian cancer invasiveness and metastasis
remains unclear. Since significant downregulation in microRNA 200 (miRNA200)
family (miR200a, miR200b, and miR200c) has been reported in the invasive ovarian
cancer cells, here, we used two human ovarian cancer cell lines, OVCAR3 and
SKOV3, to study the molecular basis of miR200, matrix metalloproteinase 3 (MMP3)
activation, and cancer invasiveness. We found that overexpression of either
miR200 family member in OVCAR3 or SKOV3 cells significantly inhibited production
and secretion of MMP3 and cancer invasiveness. Moreover, forced MMP3 expression
abolished miR200-induced inhibition of ovarian cancer cell invasiveness,
suggesting that miR200 family inhibited ovarian cell invasiveness via
downregulating MMP3. Furthermore, ZEB1, a major target of miR200, was inhibited
by miR200 overexpression. Forced ZEB1 expression abolished miR200-induced
inhibition of ovarian cancer cell invasiveness, suggesting that ZEB1 is a direct
target of miR200 for inhibiting ovarian cell invasiveness. Finally,
phosphorylated SMAD3 (pSMAD3), a major partner of ZEB1, was efficiently inhibited
by miR200, which could be restored by forced expression of ZEB1, but not by
forced expression of MMP3, suggesting that ZEB1/pSMAD3 is signaling cascade
upstream of MMP3 in this model. Taken together, our data suggest that miR200
family inhibited ovarian cancer cell invasiveness and metastasis by
downregulating MMP3, possibly through ZEB1/pSMAD3.
PMID- 25119591
TI - Novel methodologies in analysis of small molecule biomarkers and living cells.
AB - Enzyme-linked immuno-sorbent assay (ELISA) is widely used for biomarker
detection. A good biomarker can distinguish patients from healthy or benign
diseases. However, the ELISA method is not suitable for small molecule or trace
substance detection. Along with the development of new technologies, an
increasing level of biomaterials, especially small molecules, will be identified
as novel biomarkers. Quantitative immuno-PCR, chromatography-mass spectrometry,
and nucleic acid aptamer are emerging methodologies for detection of small
molecule biomarkers, even in living cells. In this review, we focus on these
novel technologies and their potential for small molecule biomarkers and living
cell analysis.
PMID- 25119593
TI - Different mutational characteristics of TSG in cell lines and surgical specimens.
AB - One of the most crucial concerns of cancer research pertains to the differences
between the neoplastic cells in tumor specimens in vivo and their counterparts in
cell lines. The huge amount of results deposited in cancer genetic databases
allows to address this issue from a wider perspective. Our analysis of the Sanger
Institute Catalog Of Somatic Mutations In Cancer (COSMIC) database v61 showed a
lower percentage of homozygous mutations in a group of tumor suppressor genes in
surgical samples (in vivo) in comparison to their frequency in cell lines (in
vitro). Similarly, the mutations resulting in the lack of protein (e.g., nonsense
mutations or whole gene deletions) of several tumor suppressor genes (TSGs) were
more frequently observed in vitro than in vivo. In this article, we suggest two
potential explanations of these data. Firstly, TSG heterozygous mutations
resulting in the modified protein (e.g., missense mutations) may be gradually
(when the specific molecular context is achieved) changed to homozygous mutations
resulting in the lack of protein during carcinogenesis. Secondly, among different
independent pathways of tumorigenesis, those leading to homozygous nonsense
mutations are characteristic for cells which are more efficiently stabilized in
vitro. To conclude, these observations may be interesting for researchers working
with cell line in vitro models illustrating the extent to which they reflect the
tumors in vivo.
PMID- 25119592
TI - Adjuvant and chemopreventive therapies for resectable hepatocellular carcinoma: a
literature review.
AB - The recurrence rate of hepatocellular carcinoma (HCC) after potentially curative
hepatic resection (HR) is very high. Many clinical trials have explored the
efficacy of several treatment modalities to prevent recurrence, including
adjuvant and chemopreventive therapy, but they have often reported contradictory
findings. As a result, most liver guidelines and liver seminars do not
unequivocally endorse adjuvant or chemopreventive therapy for HCC patients after
potentially curative HR. To examine the available evidence on this question, we
comprehensively searched PubMed for controlled studies that included a supportive
care or placebo control arm, and we used the GRADE system to classify and assess
the results.
PMID- 25119594
TI - Hsa-miR-195 targets PCMT1 in hepatocellular carcinoma that increases tumor life
span.
AB - MicroRNAs are small 19-25 nucleotides which have been shown to play important
roles in the regulation of gene expression in many organisms. Downregulation or
accumulation of miRNAs implies either tumor suppression or oncogenic activation.
In this study, differentially expressed hsa-miR-195 in hepatocellular carcinoma
(HCC) was identified and analyzed. The prediction was done using a consensus
approach of tools. The validation steps were done at two different levels in
silico and in vitro. FGF7, GHR, PCMT1, CITED2, PEX5, PEX13, NOVA1, AXIN2, and
TSPYL2 were detected with high significant (P < 0.005). These genes are involved
in important pathways in cancer like MAPK signaling pathway, Jak-STAT signaling
pathways, regulation of actin cytoskeleton, angiogenesis, Wnt signaling pathway,
and TGF-beta signaling pathway. In vitro target validation was done for protein-L
isoaspartate (D-aspartate) O-methyltransferase (PCMT1). The co-transfection of
pmirGLO-PCMT1 and pEGP-miR-195 showed highly significant results. Firefly
luciferase was detected using Lumiscensor and t test analysis was done. Firefly
luciferase expression was significantly decreased (P < 0.001) in comparison to
the control. The low expression of firefly luciferase validates the method of
target prediction that we used in this work by working on PCMT1 as a target for
miR-195. Furthermore, the rest of the predicted genes are suspected to be real
targets for hsa-miR-195. These target genes control almost all the hallmarks of
liver cancer which can be used as therapeutic targets in cancer treatment.
PMID- 25119595
TI - Podoplanin expressing cancer-associated fibroblasts in oral cancer.
AB - Podoplanin is a mucin-type glycoprotein widely used as a lymphatic endothelial
marker. It is well known that podoplanin is expressed in various neoplasms
including oral squamous cell carcinoma (OSCC). Apart from podoplanin expression
in cancer cells, recent studies have suggested that podoplanin expression in
stromal cancer-associated fibroblasts (CAFs) may be an indicator of poor
prognosis in various cancers. In the present study, we performed
immunohistochemical analyses of podoplanin and alpha-smooth muscle actin (alpha
SMA) in OSCC in order to clarify the significance of podoplanin-positive CAFs.
Paraffin-embedded tissue specimens of 69 primary and 29 corresponding metastatic
lesions in lymph nodes were examined immunohistochemically using antibodies
against podoplanin and alpha-SMA. Podoplanin-positive stromal fibroblasts were
detected in 51 (73.9%) of the 69 primary OSCCs and 24 (82.8%) of the 29 lymph
nodes metastases. alpha-SMA immunoreactivity was observed in 39 (56.5%) of the
primaries and 24 (82.8%) of the metastases. Further examination showed that 38
(74.5%) of the primary lesions and 23 (95.8%) of the metastases with podoplanin
positivity were also positive for alpha-SMA. In addition, the intensity of alpha
SMA immunoreactivity increased as that of podoplanin became stronger. Podoplanin
positive CAFs are considered to be myofibroblasts that may contribute to
progression of oral cancer.
PMID- 25119597
TI - Analysis of Tim-3 as a therapeutic target in prostate cancer.
AB - T cell immunoglobulin domain and mucin domain-containing molecule 3 (Tim-3) is a
newly discovered immunomodulatory, which plays an important role in immunity
regulation. Recent evidence suggests that Tim-3 is differentially regulated in a
variety of tumors and has a potential as a therapeutic target. The aim of this
study was to investigate the effect of Tim-3 on the development of prostate
cancer (PCa). Tim-3 expressing on peripheral CD4+ T and CD8+ T cells was analyzed
by flow cytometry. The relationships between Tim-3 expression and
clinicopathological features were analyzed. Immunohistochemical expression of Tim
3 was examined in our large numbers of paraffin-fixed prostate tissues. Flow
cytometry revealed that expression of Tim-3 was significantly increased on both
CD4+ and CD8+ T cells in PCa patients than that in benign prostate hyperplasia
(BPH) patients. Also, the level of Tim-3 on CD4+ T cells was positively
correlated with CD8+ T cells in patients. Further analyses revealed that the
levels of Tim-3 on CD4+ T cells and CD8+ T cells exhibited different expression
patterns in terms of localization depending on pathological category of PCa and
metastasis. Immunohistochemical analysis revealed that positive staining of Tim-3
in PCa but little or no staining of Tim-3 was observed in BPH epithelium. Tim-3
may affect the development and progression of PCa, which may provide knowledge
for using Tim-3 as a novel therapy for effective PCa management.
PMID- 25119598
TI - Downregulation of a long noncoding RNA-ncRuPAR contributes to tumor inhibition in
colorectal cancer.
AB - In recent years, the role of long noncoding RNAs (lncRNAs) in cancer is
increasingly focused. ncRuPAR is a newly detected lncRNA; in previous study, we
found out that ncRuPAR could inhibit tumor progression by downregulating protease
activated receptor-1 (PAR-1), but its role in colorectal cancer (CRC) is never
elucidated. Here, we conducted a self-control study which includes 105 CRC
samples. By quantitative real time PCR (qRT-PCR) and immunohistochemical
staining, we detected the expression of ncRuPAR and PAR-1 as well as their
correlation; we further associated these data with the clinicopathologic
parameters. A receiver operating characteristic (ROC) curve was constructed to
evaluate the diagnostic value of ncRuPAR and PAR-1, respectively. Our results
indicated that the expression of ncRuPAR was significantly downregulated in CRC
compared with paired adjacent nontumor tissues, but the level of PAR-1 mRNA in
cancerous tissues was significantly higher than in adjacent normal areas. The
expression of ncRuPAR was significantly correlated with lymph node metastasis,
distant metastasis, Duck's stage, differentiation, and TNM stage and was
potentially negatively associated with the mRNA levels and EI scores of PAR-1.
The area under the ROC curve of ncRuPAR was 0.81 (95% confidence interval (CI):
0.75-0.87); at a cutoff value of 8.34, the ncRuPAR measurement had a sensitivity
of 97.14%, a specificity of 65.87%, and an accuracy of 82.86% to predict CRC.
PMID- 25119596
TI - The clinical significance and regulation mechanism of hypoxia-inducible factor-1
and miR-191 expression in pancreatic cancer.
AB - The aim of study was to discuss the correlation and regulatory mechanism of HIF-1
and miR-191 expression in pancreatic tumor. The association between the miR-191
and the clinicopathologic characteristics and the prognosis of pancreatic cancer
was further explored. After hypoxic cultured for 6 and 12 h, qRT-PCR and Western
blot were practiced to analyze the miR-191 and HIF-1 expression of MIA PaCa-2 and
Aspac1 cells. We regulated the HIF-1 expression via plasmid and siRNA
transfection to observe the alteration of HIF-1 and miR-191 expression. ChIP
sequencing identified the binding sites of HIF-1 and miR-191. Dual luciferase
assays were practiced to verify the binding sites. Immunohistochemical staining
was practiced to analyze the expression of HIF-1, while qRT-PCR were done for
investigating miR-191 in tumor tissues. Then, the association between the
expression of them and the clinicopathologic characteristics and prognosis of
pancreatic cancer were analyzed. After hypoxic cultured 12 h, the expression of
HIF-1 protein, HIF-1mRNA and miR-191 of MIA PaCa-2 and AsPC-1 cells increased
significantly (P < 0.05). After HIF-1 overexpressing plasmid transfected to the
MIA PaCa-2 and AsPC-1 cells for 48 h, the expression of HIF-1 protein, HIF-1mRNA,
and miR-191 upregulated significantly (P < 0.05). While after transfected the MIA
PaCa-2 cells by HIF-1 siRNA, the significant decreasing of HIF-1 protein, HIF
1mRNA, and miR-191 expression were observed (P < 0.05). ChIP sequencing showed
the protein synthesis of HIF-1 increased in hypoxia situation. Only the HRE5 (
1,169 bp, ChIP4) were significantly brighter in hypoxia in comparing with
normoxic cells. In dual luciferase assays, after pGL3-miR-191 and HIF-1
overexpressing plasmid co-transfect the MIAPaCa-2 cells for 48 h, its relative
expression of bioluminescence was higher than those co-transfected by mutant miR
191 vectors and HIF-1 overexpressing plasmid or by pGL3-miR-191 and HIF-1 empty
plasmid. The expression of miR-191 closely associated with the tumor size, pTNM
stage, lymph node metastasis, and perineural invasion (P < 0.05). Patients with
higher expression of miR-191 were a risk factor for prognosis of pancreatic
cancers. Expression of HIF-1 in pancreatic cancer cells increased under the
condition of chronic hypoxia, which may bind to HRE2 in 5'flanking region of miR
191 and initiate transcription of miR-191. Expression of miR-191 was
significantly higher in pancreatic tumor tissues. The expression of miR-191
closely associated with the tumor size, pTNM stage, lymph node metastasis and
perineural invasion and poor prognosis of pancreatic cancer.
PMID- 25119599
TI - miR-152 suppresses gastric cancer cell proliferation and motility by targeting
CD151.
AB - We aimed to study the post-translational regulation of CD151 by the microRNA miR
152. CD151 is highly expressed in gastric cancer (GC) and has been shown to
accelerate GC by enhancing invasion and metastasis; however, its regulation is
still unclear. Our results showed decreased expression of miR-152 in GC tissue
samples and cell lines. In addition, miR-152 complementation significantly
inhibits both the proliferation and motility of GC cells. CD151 was found to be a
target of miR-152, and overexpression of CD151 attenuated the suppressive effect
of miR-152. Our findings highlight an essential role of miR-152 in the regulation
of proliferation and motility of GC cells and suggest a potential application of
miR-152 in GC treatment.
PMID- 25119600
TI - TES was epigenetically silenced and suppressed the epithelial-mesenchymal
transition in breast cancer.
AB - The TES gene was frequently lost in breast cancer, which could inhibit tumor
invasion and the formation of distant metastasis. However, the underlying
mechanisms remain unknown yet. In the present study, we aimed to investigate how
TES was silenced and its roles in EMT--the key step for tumor metastasis. Real
time polymerase chain reaction (PCR) and Western blot were used to detect the
mRNA and protein expression of target genes; the status of TES promoter was
determined by methylation-specific PCR and subsequently, DNA sequencing.
Overexpression or downregulation of TES was achieved by pcDNA3.1-TES or shRNA-TES
transfection. Cellular adhesion and migration were investigated by the adhesion
and Transwell assays. Morphological changes of breast cancer cells were observed
under the optical microscope. The Rho A activity was measured using a commercial
kit, and its roles in TES-manipulated EMT were determined by real-time PCR and
Western blot. The 42.3% (33/78) breast cancer tissues presented hypermethylation
of the TES gene, whereas only 2 (2.6%) non-malignant cases were hypermethylated
(P<0.001). Moreover, TES hypermethylation was significantly correlated with
larger tumor diameter (P=0.03) and lympho node metastasis (P=0.024). In primary
cultured breast cancer cells, the demethylation treatment using 5-aza-dC notably
restored the expression of TES. In vitro, overexpression of TES enhanced cellular
adhesion inhibited migration and suppressed EMT, while downregulation of TES
impaired cellular adhesion, promoted migration, and enhanced EMT. TES
overexpression also activated the Rho A signal, which is a critical factor for
the effects of TES on the EMT procedure. We firstly proved that frequent loss of
TES in breast cancer was caused by promoter hypermethylation, which was
correlated with poor prognosis. In vitro, TES enhanced cellular adhesion,
suppressed tumor migration, and inhibited EMT. Moreover, the Rho A pathway was
critical for the effects of TES on EMT, which can be blocked by the Rho A
inhibitor. Therefore, we propose restoration of TES as a potent strategy for
breast cancer therapy.
PMID- 25119601
TI - Armc8 expression was elevated during atypia-to-carcinoma progression and
associated with cancer development of breast carcinoma.
AB - Armadillo repeat-containing protein 8 (Armc8) is a key factor to regulate cell
membrane adhesion complex through promoting alpha-catenin degradation. However,
its expression and function in human malignant tumors are largely unknown. Here,
we present our study investigating Armc8 expression in tumor and non-tumor breast
tissues including 45 normal epithelia, 53 lesions of hyperplasia with or without
dysplasia, 22 benign tumors, and 92 carcinomas including 28 carcinomas in situ
and 64 infiltrating carcinomas using immunohistochemistry (IHC) and Western
blotting study. Armc8 expression was detected mainly in the cytoplasm with
occasional membrane immunostaining. The positive rate of Armc8 expression in
normal breast epithelia (8.9%, four out of 45) was very low. No significant
difference was found between Armc8 expression in usual ductal hyperplasia (UDH)
(11.1%, two out of 18), benign breast tumors including intraductal papilloma
(10.0%, one out of 10) and fibroadenoma (8.3%, one out of 12), and normal breast
epithelia (p>0.05). Elevated expression of Armc8 was found in breast epithelia
with dysplasia (24.0%, six out of 25) compared to that in normal breast
epithelia, UDH, and benign breast tumors (p<0.05). Armc8 expression in breast
carcinoma including breast carcinoma in situ (10/28, 35.7%), infiltrating ductal
carcinoma (60.7%, 34/56), and infiltrating lobular carcinoma (50.0%, 4/8) was
higher than that in normal breast epithelia, UDH, benign breast tumors, and
breast epithelia with dysplasia (p<0.05). The highest expression of Armc8 was
found in infiltrating breast carcinoma (59.4%, 38/64) compared to all the other
breast tissues. Higher Armc8 expression was found to be linked to lymph node
metastasis and advanced tumor-node-metastasis (TNM) stages (III+IV) in
infiltrating breast carcinoma (p<0.05). We further confirmed Armc8 expression in
breast epithelial cell line MCF10A and breast carcinoma cell lines including MCF
7, MDA-MB-231, and ZR751 using Western blotting and immunofluorescent study.
These results indicate that the elevated expression of Armc8 may be involved in
carcinogenesis including atypia-to-carcinoma progression and cancer development
of breast carcinoma.
PMID- 25119603
TI - In Vitro and in vivo characterization of wireless and passive micro system
enabling gastrointestinal pressure monitoring.
AB - This paper presents a wireless and passive micro pressure system based on the LC
mutual inductance detection mechanism for gastrointestinal (GI) pressure
monitoring. The micro pressure system is composed of a sensor capsule (a pressure
sensitive micro capacitive sensor in series with an induction coil to form an LC
tank) and a detection unit (a detection coil connected with a network analyzer).
The pressure variations under measurement lead to changes in the capacitance of
the pressure sensor and therefore a shift in the LC tank resonant frequency,
quantified by the impedance measurement of the detection coil. The pressure
sensor was fabricated using microfabrication processes with key parameters
optimized. The in vitro characterization of the micro pressure system recorded a
sensitivity of 0.2491 kHz/kPa (-10 kPa to 30 kPa). One-month rabbit stomach
pressure monitoring was conducted based on the developed micro pressure system as
a confirmation of device long term in vivo stability. Furthermore, rabbit stomach
pressure variations before and after food feeding was recorded and compared where
three distinctive contraction patterns (random contraction with low amplitude,
irregular strong contractions and regular contraction in a cyclic manner)
following food feeding were located. Compared to previous reported GI pressure
sensors, this LC tank is featured with simple device structure without batteries
and electrical components for energy transfer. Both in vitro and in vivo
characterization confirm the functionality of the system, which may enable the
gastrointestinal motility study in the near future.
PMID- 25119602
TI - Chronic atrophic gastritis in association with hair mercury level.
AB - The objective of this study was to explore hair mercury level in association with
chronic atrophic gastritis, a precancerous stage of gastric cancer (GC), and thus
provide a brand new angle of view on the timely intervention of precancerous
stage of GC. We recruited 149 healthy volunteers as controls and 152 patients
suffering from chronic gastritis as cases. The controls denied upper
gastrointestinal discomforts, and the cases were diagnosed as chronic superficial
gastritis (n=68) or chronic atrophic gastritis (n=84). We utilized Mercury
Automated Analyzer (NIC MA-3000) to detect hair mercury level of both healthy
controls and cases of chronic gastritis. The statistic of measurement data was
expressed as mean +/- standard deviation, which was analyzed using Levene
variance equality test and t test. Pearson correlation analysis was employed to
determine associated factors affecting hair mercury levels, and multiple stepwise
regression analysis was performed to deduce regression equations. Statistical
significance is considered if p value is less than 0.05. The overall hair mercury
level was 0.908949 +/- 0.8844490 ng/g [mean +/- standard deviation (SD)] in
gastritis cases and 0.460198 +/- 0.2712187 ng/g (mean+/-SD) in healthy controls;
the former level was significantly higher than the latter one (p=0.000<0.01). The
hair mercury level in chronic atrophic gastritis subgroup was 1.155220 +/-
0.9470246 ng/g (mean +/- SD) and that in chronic superficial gastritis subgroup
was 0.604732 +/- 0.6942509 ng/g (mean +/- SD); the former level was significantly
higher than the latter level (p<0.01). The hair mercury level in chronic
superficial gastritis cases was significantly higher than that in healthy
controls (p<0.05). The hair mercury level in chronic atrophic gastritis cases was
significantly higher than that in healthy controls (p<0.01). Stratified analysis
indicated that the hair mercury level in healthy controls with eating seafood was
significantly higher than that in healthy controls without eating seafood
(p<0.01) and that the hair mercury level in chronic atrophic gastritis cases was
significantly higher than that in chronic superficial gastritis cases (p<0.01).
Pearson correlation analysis indicated that eating seafood was most correlated
with hair mercury level and positively correlated in the healthy controls and
that the severity of gastritis was most correlated with hair mercury level and
positively correlated in the gastritis cases. Multiple stepwise regression
analysis indicated that the regression equation of hair mercury level in controls
could be expressed as 0.262 multiplied the value of eating seafood plus 0.434,
the model that was statistically significant (p<0.01). Multiple stepwise
regression analysis also indicated that the regression equation of hair mercury
level in gastritis cases could be expressed as 0.305 multiplied the severity of
gastritis, the model that was also statistically significant (p<0.01). The graphs
of regression standardized residual for both controls and cases conformed to
normal distribution. The main positively correlated factor affecting the hair
mercury level is eating seafood in healthy people whereas the predominant
positively correlated factor affecting the hair mercury level is the severity of
gastritis in chronic gastritis patients. That is to say, the severity of chronic
gastritis is positively correlated with the level of hair mercury. The
incessantly increased level of hair mercury possibly reflects the development of
gastritis from normal stomach to superficial gastritis and to atrophic gastritis.
The detection of hair mercury is potentially a means to predict the severity of
chronic gastritis and possibly to insinuate the environmental mercury threat to
human health in terms of gastritis or even carcinogenesis.
PMID- 25119604
TI - Adverse effects of prohibiting narrow provider networks.
AB - Many insurers participating in the new insurance exchanges are controlling costs
by offering plans with narrow provider networks. Proposed regulations would
promote network adequacy, but a pro-provider stance may not be inherently pro
consumer or even pro-patient.
PMID- 25119605
TI - Genotype-phenotype correlation--promiscuity in the era of next-generation
sequencing.
AB - Newly cost-effective next-generation sequencing has led to an explosion of
discoveries of novel genetic mutations that reveal the rampant "promiscuity" of
genotype-phenotype relationships. Such discoveries should ultimately
revolutionize clinical care.
PMID- 25119609
TI - Efficacy of high-dose versus standard-dose influenza vaccine in older adults.
AB - BACKGROUND: As compared with a standard-dose vaccine, a high-dose, trivalent,
inactivated influenza vaccine (IIV3-HD) improves antibody responses to influenza
among adults 65 years of age or older. This study evaluated whether IIV3-HD also
improves protection against laboratory-confirmed influenza illness. METHODS: We
conducted a phase IIIb-IV, multicenter, randomized, double-blind, active
controlled trial to compare IIV3-HD (60 MUg of hemagglutinin per strain) with
standard-dose trivalent, inactivated influenza vaccine (IIV3-SD [15 MUg of
hemagglutinin per strain]) in adults 65 years of age or older. Assessments of
relative efficacy, effectiveness, safety (serious adverse events), and
immunogenicity (hemagglutination-inhibition [HAI] titers) were performed during
the 2011-2012 (year 1) and the 2012-2013 (year 2) northern-hemisphere influenza
seasons. RESULTS: A total of 31,989 participants were enrolled from 126 research
centers in the United States and Canada (15,991 were randomly assigned to receive
IIV3-HD, and 15,998 to receive IIV3-SD). In the intention-to-treat analysis, 228
participants in the IIV3-HD group (1.4%) and 301 participants in the IIV3-SD
group (1.9%) had laboratory-confirmed influenza caused by any viral type or
subtype associated with a protocol-defined influenza-like illness (relative
efficacy, 24.2%; 95% confidence interval [CI], 9.7 to 36.5). At least one serious
adverse event during the safety surveillance period was reported by 1323 (8.3%)
of the participants in the IIV3-HD group, as compared with 1442 (9.0%) of the
participants in the IIV3-SD group (relative risk, 0.92; 95% CI, 0.85 to 0.99).
After vaccination, HAI titers and seroprotection rates (the percentage of
participants with HAI titers >= 1:40) were significantly higher in the IIV3-HD
group. Conclusions: Among persons 65 years of age or older, IIV3-HD induced
significantly higher antibody responses and provided better protection against
laboratory-confirmed influenza illness than did IIV3-SD. (Funded by Sanofi
Pasteur; ClinicalTrials.gov number, NCT01427309.).
PMID- 25119610
TI - Clinical practice: Obsessive-compulsive disorder.
AB - A 19-year-old man is brought to his primary physician by his father, who explains
that his son washes his hands a hundred times a day, will not touch anything that
has been touched by someone else without scrubbing it first, and has a fear of
germs that has left him isolated in his bedroom, unable to eat, and wishing he
were dead. Although the father reports that his son has always been finicky, this
problem started approximately 2 years ago and has gradually become completely
disabling. How should this patient be evaluated and treated?
PMID- 25119611
TI - Syndromes of thrombotic microangiopathy.
AB - This review article covers the diverse pathophysiological pathways that can lead
to microangiopathic hemolytic anemia and a procoagulant state with or without
damage to the kidneys and other organs.
PMID- 25119612
TI - Images in clinical medicine: Syphilitic gumma.
AB - A 45-year-old woman presented to a clinic in rural Uganda with a 1-year history
of a progressively enlarging ulcerated mass on the hard palate. The mass had
initially been painless but recently had become painful and was causing
difficulty in speaking and swallowing.
PMID- 25119608
TI - Global sodium consumption and death from cardiovascular causes.
AB - BACKGROUND: High sodium intake increases blood pressure, a risk factor for
cardiovascular disease, but the effects of sodium intake on global cardiovascular
mortality are uncertain. METHODS: We collected data from surveys on sodium intake
as determined by urinary excretion and diet in persons from 66 countries
(accounting for 74.1% of adults throughout the world), and we used these data to
quantify the global consumption of sodium according to age, sex, and country. The
effects of sodium on blood pressure, according to age, race, and the presence or
absence of hypertension, were calculated from data in a new meta-analysis of 107
randomized interventions, and the effects of blood pressure on cardiovascular
mortality, according to age, were calculated from a meta-analysis of cohorts.
Cause-specific mortality was derived from the Global Burden of Disease Study
2010. Using comparative risk assessment, we estimated the cardiovascular effects
of current sodium intake, as compared with a reference intake of 2.0 g of sodium
per day, according to age, sex, and country. RESULTS: In 2010, the estimated mean
level of global sodium consumption was 3.95 g per day, and regional mean levels
ranged from 2.18 to 5.51 g per day. Globally, 1.65 million annual deaths from
cardiovascular causes (95% uncertainty interval [confidence interval], 1.10
million to 2.22 million) were attributed to sodium intake above the reference
level; 61.9% of these deaths occurred in men and 38.1% occurred in women. These
deaths accounted for nearly 1 of every 10 deaths from cardiovascular causes
(9.5%). Four of every 5 deaths (84.3%) occurred in low- and middle-income
countries, and 2 of every 5 deaths (40.4%) were premature (before 70 years of
age). The rate of death from cardiovascular causes associated with sodium intake
above the reference level was highest in the country of Georgia and lowest in
Kenya. CONCLUSIONS: In this modeling study, 1.65 million deaths from
cardiovascular causes that occurred in 2010 were attributed to sodium consumption
above a reference level of 2.0 g per day. (Funded by the Bill and Melinda Gates
Foundation.).
PMID- 25119613
TI - Case Records of the Massachusetts General Hospital. Case 25-2014. A 37-year-old
man with ulcerative colitis and bloody diarrhea.
AB - A 37-year-old man with ulcerative colitis was admitted to the hospital because of
abdominal cramping, diarrhea, hematochezia, fever to a peak temperature of 38.8
degrees C, and drenching night sweats. Several weeks earlier, he had performed
home fecal transplantation.
PMID- 25119614
TI - Low sodium intake--cardiovascular health benefit or risk?
PMID- 25119606
TI - Association of urinary sodium and potassium excretion with blood pressure.
AB - BACKGROUND: Higher levels of sodium intake are reported to be associated with
higher blood pressure. Whether this relationship varies according to levels of
sodium or potassium intake and in different populations is unknown. METHODS: We
studied 102,216 adults from 18 countries. Estimates of 24-hour sodium and
potassium excretion were made from a single fasting morning urine specimen and
were used as surrogates for intake. We assessed the relationship between
electrolyte excretion and blood pressure, as measured with an automated device.
RESULTS: Regression analyses showed increments of 2.11 mm Hg in systolic blood
pressure and 0.78 mm Hg in diastolic blood pressure for each 1-g increment in
estimated sodium excretion. The slope of this association was steeper with higher
sodium intake (an increment of 2.58 mm Hg in systolic blood pressure per gram for
sodium excretion >5 g per day, 1.74 mm Hg per gram for 3 to 5 g per day, and 0.74
mm Hg per gram for <3 g per day; P<0.001 for interaction). The slope of
association was steeper for persons with hypertension (2.49 mm Hg per gram) than
for those without hypertension (1.30 mm Hg per gram, P<0.001 for interaction) and
was steeper with increased age (2.97 mm Hg per gram at >55 years of age, 2.43 mm
Hg per gram at 45 to 55 years of age, and 1.96 mm Hg per gram at <45 years of
age; P<0.001 for interaction). Potassium excretion was inversely associated with
systolic blood pressure, with a steeper slope of association for persons with
hypertension than for those without it (P<0.001) and a steeper slope with
increased age (P<0.001). CONCLUSIONS: In this study, the association of estimated
intake of sodium and potassium, as determined from measurements of excretion of
these cations, with blood pressure was nonlinear and was most pronounced in
persons consuming high-sodium diets, persons with hypertension, and older
persons. (Funded by the Heart and Stroke Foundation of Ontario and others.).
PMID- 25119615
TI - Bariatric surgery versus intensive medical therapy for diabetes.
PMID- 25119616
TI - Bariatric surgery versus intensive medical therapy for diabetes.
PMID- 25119617
TI - Bariatric surgery versus intensive medical therapy for diabetes.
PMID- 25119618
TI - Bariatric surgery versus intensive medical therapy for diabetes.
PMID- 25119607
TI - Urinary sodium and potassium excretion, mortality, and cardiovascular events.
AB - BACKGROUND: The optimal range of sodium intake for cardiovascular health is
controversial. METHODS: We obtained morning fasting urine samples from 101,945
persons in 17 countries and estimated 24-hour sodium and potassium excretion
(used as a surrogate for intake). We examined the association between estimated
urinary sodium and potassium excretion and the composite outcome of death and
major cardiovascular events. RESULTS: The mean estimated sodium and potassium
excretion was 4.93 g per day and 2.12 g per day, respectively. With a mean follow
up of 3.7 years, the composite outcome occurred in 3317 participants (3.3%). As
compared with an estimated sodium excretion of 4.00 to 5.99 g per day (reference
range), a higher estimated sodium excretion (>= 7.00 g per day) was associated
with an increased risk of the composite outcome (odds ratio, 1.15; 95% confidence
interval [CI], 1.02 to 1.30), as well as increased risks of death and major
cardiovascular events considered separately. The association between a high
estimated sodium excretion and the composite outcome was strongest among
participants with hypertension (P=0.02 for interaction), with an increased risk
at an estimated sodium excretion of 6.00 g or more per day. As compared with the
reference range, an estimated sodium excretion that was below 3.00 g per day was
also associated with an increased risk of the composite outcome (odds ratio,
1.27; 95% CI, 1.12 to 1.44). As compared with an estimated potassium excretion
that was less than 1.50 g per day, higher potassium excretion was associated with
a reduced risk of the composite outcome. CONCLUSIONS: In this study in which
sodium intake was estimated on the basis of measured urinary excretion, an
estimated sodium intake between 3 g per day and 6 g per day was associated with a
lower risk of death and cardiovascular events than was either a higher or lower
estimated level of intake. As compared with an estimated potassium excretion that
was less than 1.50 g per day, higher potassium excretion was associated with a
lower risk of death and cardiovascular events. (Funded by the Population Health
Research Institute and others.).
PMID- 25119619
TI - Bariatric surgery versus intensive medical therapy for diabetes.
PMID- 25119620
TI - Aortic dilatation with bicuspid aortic valve.
PMID- 25119622
TI - Lyme disease.
PMID- 25119623
TI - Lyme disease.
PMID- 25119621
TI - Lyme disease.
PMID- 25119624
TI - Activated protein C resistance assay and factor V Leiden.
AB - The authors suggest that functional testing for activated protein C resistance is
cheaper and more clinically relevant than genetic testing to detect a factor V
Leiden mutation in identifying persons who are at risk for thromboembolism.
PMID- 25119625
TI - Images in clinical medicine: Morphologic changes in erythrocytes in
hypertriglyceridemia.
AB - A 39-year-old woman with a history of gestational diabetes was admitted with
epigastric pain from acute pancreatitis. She had no history of hyperlipidemia,
but multiple blood samples were grossly lipemic, and serum triglyceride levels
were markedly increased.
PMID- 25119626
TI - Reinforcement with fascia lata as an alternative in the repair of chronic
quadriceps tendon injuries.
PMID- 25119627
TI - The Role and Influence of Faith Leaders on Health-Related Issues and Programs in
their Congregation.
AB - This qualitative study explored the influence of faith leaders on health-related
issues within their congregation. Semi-structured interviewers with 24 faith
leaders found that chronic conditions and poor health behaviors were the top
health challenges facing their congregation. A majority mentioned health-related
activities taking place at their church. Most believed they had influence on
their congregation for issues related to health/wellness, most commonly in the
form of increasing awareness. A majority talked about the importance of being a
role model. It is important to understand how to most effectively capitalize on
the strengths of and engage pastors in health promotion efforts.
PMID- 25119628
TI - Increased congregational support for parents of children with cystic fibrosis.
AB - Positive health outcomes are related to adults' religious congregational
participation. For parents of children with chronic disease, structured daily
care routines and/or strict infection control precautions may limit
participation. For this exploratory study, we examined the relationship between
congregational support and religious coping by parents of children with cystic
fibrosis (CF) compared to parents for whom child health issues were not
significant stressors. CF parents reported higher levels of emotional support
from congregation members and use of religious coping. Within-group differences
were found for CF parents by denominational affiliation. Congregational support
for parents dealing with child chronic disease is important.
PMID- 25119629
TI - [Heatstroke in dogs in southern Germany. A retrospective study over a 5.5-year
period].
AB - OBJECTIVE: Heatstroke is a life-threating emergency in dogs. The aim of this
retrospective study was to analyse the sources of heat stroke in dogs,
predisposing and prognostic factors, results of physical examination and clinical
pathology as well as the course of this condition and appropriate treatment.
MATERIAL AND METHODS: Patient histories of 12 dogs diagnosed with heat stroke
over a 5.5-year period were analysed retrospectively. Normality was tested using
the Kolmogrow-Smirnow Test and analysed using T-tests, the Chi-square test and
the Mann-Whitney U-test. P-values < 0.05 were considered significant. RESULTS:
Heat stroke occurred most frequently during summer, particularly in the
afternoon. The most common cause of heat stroke was heat exposition in a car.
Brachycephalic breeds were overrepresented. The most common clinical signs were
polypnoea, tachycardia, hyperthermia and depression to prostration as well as
gastrointestinal and neurological symptoms. Clinical pathology results included
haemoconcentration, thrombocytopenia, hyperkalemia, prolonged activated partial
thromboplastin time and azotemia. Therapies employed included oxygen application,
cooling, fluid therapy and administration of gastrointestinal protectants,
antiemetics and antibiotics. Duration of hospitalization was 1-6 days. The
overall mortality rate was 50%. Most of the non-survivors died or were euthanized
within 24-48 hours after presentation. All animals remaining alive after 3 days
survived and could be discharged from hospital. CLINICAL RELEVANCE: Heat stroke
is a life-threating condition, which can lead to shock, sepsis, coagulation
disorders and multiorgan failure. Early recognition and appropriate treatment are
important factors for a positive outcome. Furthermore, intensive monitoring and
rapid therapy adaption as required are pivotal.
PMID- 25119631
TI - Feline lower urinary tract disease in a German cat population. A retrospective
analysis of demographic data, causes and clinical signs.
AB - OBJECTIVE: To investigate epidemiologic data, clinical signs, results of
urinalysis and causes of lower urinary tract disease in a German veterinary
hospital population of cats and to determine if the demographic data, history,
clinical signs and urinalysis results correlate with a particular etiology.
MATERIALS AND METHODS: Cats presented with signs of feline lower urinary tract
disease (FLUTD) with a documented history and physical examination, a complete
urinalysis (urine specific gravity, urine dipstick and sediment, urine culture)
of urine obtained by cystocentesis or catheterization, and diagnostic imaging of
the urinary tract were included into the study. Cats that had received a previous
treatment during the same episode of FLUTD were excluded. RESULTS: A total of 302
cats were included into the study. Cats with FLUTD presented throughout the
seasons with similar frequency. The most common diagnosis was feline idiopathic
cystitis (FIC) (55.0%), followed by bacterial urinary tract infection (UTI)
(18.9%), urethral plug (10.3%) and urolithiasis (7.0%). Urethral obstruction was
significantly more frequent in cats with FIC than in cats with UTI. Cats with FIC
and urethral plugs were significantly younger and had significantly higher body
weights than cats with UTI and neoplasia. FIC and urethral plugs were
significantly more common causes of FLUTD in cats younger than 10 years compared
to cats that were 10 years or older (65.2% versus [vs.] 35.8% and 13.3% vs.
3.0%), while the incidences of UTI and neoplasia increased with age (12.9% vs.
41.8% and 1.0% vs. 13.4%). CONCLUSION AND CLINICAL RELEVANCE: FIC and UTI are the
most common diagnoses in cats with FLUTD, with a significant age-related
difference in incidence.
PMID- 25119632
TI - [New drugs for small animals in 2013].
AB - In 2013, four active pharmaceutical ingredients were released on the German
market for small animals. Those are the recombinant human bone morphogenetic
protein-2 dibotermin alfa (TruScient(r)), the ectoparasiticide of the oxadiazine
group indoxacarb (Activyl(r)), the antiepileptic imepitoin (Pexion(r)) and the
angiotensin-II1-receptor antagonist telmisartan (Semintra(r)). One substance was
authorized for an additional species. The prolactin antagonist cabergoline is now
also authorized for use in cats. In addition, three active pharmaceutical
ingredients, which were approved in 2013 for use in human medicine and are of
potential interest to veterinary medicine, are discussed. These are the
antineoplastic ingredients dabrafenib, enzalutamide and vismodegib.
PMID- 25119630
TI - Diagnostic efficacy of the leukogram and the chemiluminometric ACTH measurement
to diagnose canine hypoadrenocorticism.
AB - BACKGROUND AND OBJECTIVE: The gold standard in the diagnosis of canine
hypoadrenocorticism (HA) is the adrenocorticotropin (ACTH) response test. As
synthetic ACTH (tetracosactide [Synacthen(r)]) is currently not available in the
European Union, the evaluation of other diagnostic tests seemed warranted. The
diagnostic efficacy of electrolytes, the leukogram and endogenous ACTH
concentrations to diagnose HA was investigated. MATERIAL AND METHODS: The medical
records of 145 dogs with clinical signs suspect for spontaneous HA were included
in a retrospective study. HA was diagnosed (n = 38) or ruled out (n = 84) by
using an ACTH response test. In 23 patients HA was excluded by basal cortisol
measurement. The diagnostic performance of various variables was assessed based
on receiver operating characteristic (ROC) curves and by calculating differential
positive rates. A decision tree (IBM SPSS Decision Trees 20, IBM Corporation) was
constructed with the variables neutrophil to lymphocyte ratio (N/LR) and sodium
to potassium ratio (Na/KR) to illustrate the diagnostic efficacy of the
respective test results. RESULTS: The best single variables to diagnose HA were
the endogenous ACTH concentration (area under the ROC curve [ROC AUC] 0.97;
cutoff > 50 pmol/l: sensitivity 96%, specificity 100%) and the Na/KR (ROC AUC
0.905; cutoff <= 22: sensitivity 92%, specificity 91%). The diagnostic
performance of various variables of the leukogram was poor to moderate (ROC AUC
0.625-0.828). 68% of dogs with HA had a Na/KR <= 22 and a N/LR <= 2.3, a
combination not observed in dogs with non-adrenal diseases. CONCLUSION AND
CLINICAL RELEVANCE: As secondary HA is very rare, endogenous ACTH measurement is
a very good alternative to the traditional ACTH response test. Data also suggest
that the combination of a Na/KR <= 22 and a N/LR <= 2.3 is highly specific and
can be used to rule in HA.
PMID- 25119633
TI - [Porencephaly in a female Greater Swiss Mountain Dog].
AB - A 15-month-old female Greater Swiss Mountain Dog was presented after an epileptic
episode. In addition, the owner had noticed a recent marked change in the
animal's behaviour. Because of the progressive nature of the neurological signs,
a magnetic resonance imaging scan of the brain was performed and porencephaly in
the parietal lobe of the right hemisphere was diagnosed. The dog was euthanized
and submitted for pathology. Because of the histopathological findings and the
history of a craniocerebral injury whilst a puppy, a traumatic genesis of this
rare cystic lesion is discussed.
PMID- 25119634
TI - [Ovarian tumor in a koi carp (Cyprinus carpio): Diagnosis, surgery, postoperative
care and tumour classification].
AB - Although ovarian tumour in the koi (Cyprinus carpio) does not appear to be an
uncommon condition, its occurrence and therapy has rarely been reported. In the
present case, the decision for surgery was based on clinical and sonographic
findings of an intracoelomic mass. We used tricaine methansulfonate for the
anaesthesia. Laparotomy was performed by ventral access and an ovarian tumour of
12-cm diameter was removed. The wound was sutured in two layers using Vicryl(r).
In addition to the application of an analgesic, an antibiotic and vitamins, the
postoperative conditions the patient was kept under were adapted to support wound
healing. The fish recovered uneventfully and was clinically healthy during the 16
month observation period. Based on the histological findings, the tumour was
diagnosed as a thecoma. Investigations using antibodies against vimentin,
cytokeratin, S 100 and glial fibrillary acidic protein (GFAP) failed to provide
reliable results.
PMID- 25119635
TI - [Evidence-based guidelines for cardio-pulmonary resuscitation in the dog and
cat].
AB - Early recognition of a cardio-pulmonary arrest (CPA) is crucial for patient
survival. Every non-breathing and non-responsive patient should be considered to
have CPA, and examination of the vital signs should last no longer than 5-10
seconds. If in doubt, effective chest compressions should be started immediately
(frequency of 100-120 compressions per minute, compression depth one third to
half of the chest diameter, full chest wall recoil between the compressions, no
interruption, change of compressing person every 2 minutes). Furthermore, the
patient should be intubated and ventilated as early as possible with a frequency
of 10 breaths per minute and a volume of 10 ml/kg. Additional measures include
monitoring (electrocardiogram, end-expiratory carbon dioxide concentration),
placement of an intravenous or intraosseous catheter, administration of opioid-,
benzodiazepine- and/or alpha2-antagonists and ECG-dependent therapy to restore
spontaneous circulation. In the case of asystole and pulseless electric activity,
epinephrine (0.01 mg/kg every 3-5 minutes, alternative dose concept: 0.1 mg/kg
epinephrine) is advised. In the case of CPA due to elevated vagal tonus or
bradycardia, atropine should be given (0.04 mg/kg every 3-5 minutes). If
ventricular fibrillation or pulseless ventricular tachyarrhythmia is present,
defibrillation is the therapy of choice. When this is not possible, amiodarone (5
mg/kg) or lidocaine (2 mg/kg) should be administered. Furthermore, 100% oxygen
should be given during resuscitation, while only a few patients benefit from
infusion therapy. Following the return of spontaneous circulation, intensive care
of the patient is necessary. This involves intense monitoring and support of the
haemodynamic situation using intravenous fluids, vasopressors and positive
inotropic drugs as well as an improvement of gas exchange and neuroprotection.
PMID- 25119636
TI - Fluorescence in situ hybridization of chromosome 17 polysomy in breast cancer
using thin tissue sections causes the loss of CEP17 and HER2 signals.
AB - Human epidermal growth factor receptor 2 (HER2 gene) and chromosome 17 polysomy
are associated with breast cancer prognosis, chemotherapy and hormone therapy.
HER2 gene analysis using fluorescence in situ hybridization (FISH) with 4-um
sections assuming a nuclear diameter of 6 um caused the loss of genetic DNA.
Using intact whole nuclei FISH (WNFISH) and thin tissue section FISH (TTFISH),
109 cases of invasive breast cancer were examined to observe correlations among
HER2 gene amplification, CEP17 polysomy and the HER2/CEP17 ratio. The results
showed significant differences in the mean copy number of HER2 and the HER2/CEP17
ratios between the WNFISH and TTFISH groups. No significant differences were
observed in HER2 amplified, equivocal and non-amplified HER2 samples. Thirty
seven cases of CEP17 polysomy and 72 cases of non-polysomy were detected by
WNFISH. Twenty-nine cases of CEP17 polysomy and 72 cases of non-polysomy were
detected by TTFISH. Significant differences were observed between the two methods
using the McNemar test (P=0.039). In conclusion, detection of chromosome 17
polysomy in breast cancer with fluorescence in situ hybridization using thin
tissue sections may cause the loss of CEP17 and HER2 signals.
PMID- 25119637
TI - Neuroprogression and staging in psychiatry: historical considerations.
PMID- 25119638
TI - Looking beyond the prevalence of depression in Brazil: are we prepared to go
further?
PMID- 25119639
TI - Prevalence of depression morbidity among Brazilian adults: a systematic review
and meta-analysis.
AB - OBJECTIVE: To estimate the prevalence of depressive symptoms and major depressive
disorder, as assessed in population-based cross-sectional studies of Brazilian
adults. METHODS: We performed a systematic review of the literature. The major
databases were searched up through October 2013. Two researchers selected the
studies, extracted the data, and assessed their methodological quality. Meta
analyses were performed using random effects. RESULTS: Of the 2,971 records
retrieved, we selected 27 studies that assessed the prevalence of depression
morbidity in 464,734 individuals (66% women). Eleven different screening tools
were used to assess depression morbidity. The prevalence of depressive symptoms
was 14% (95% confidence interval [95%CI] 13-16; I2 = 99.5%), whereas the 1-year
prevalence of major depressive disorder was 8% (95%CI 7-10; I2 = 86.7%), and the
lifetime prevalence of major depressive disorder was 17% (95%CI 14-19; I2 =
91.6%). All rates were higher in women than in men. No causes of heterogeneity
could be identified. CONCLUSION: Depression morbidity was common among Brazilian
adults, and affects more women than men. Inconsistencies across studies highlight
the need for standardization of future research. Clinicians should routinely
investigate for the presence of depression morbidity in this population.
PMID- 25119640
TI - Will the DSM-5 changes in criteria for premenstrual dysphoric disorder impact
clinical practice?
PMID- 25119641
TI - Obsessive-compulsive disorder in fathers during pregnancy and postpartum.
PMID- 25119642
TI - Developmental disability in schoolchildren from four Brazilian regions.
PMID- 25119643
TI - Mental health of refugees: report of a successful case in Brazil.
PMID- 25119645
TI - Direct observation of OH formation from stabilised Criegee intermediates.
AB - The syn-CH3CHOO Criegee intermediate formed from the ozonolysis of propene and
(E)-2-butene was detected via unimolecular decomposition and subsequent detection
of OH radicals by a LIF-FAGE instrument. An observed time dependent OH
concentration profile was analysed using a detailed model focusing on the
speciated chemistry of Criegee intermediates based on the recent literature. The
absolute OH concentration was found to depend on the steady state concentration
of syn-CH3CHOO at the injection point while the time dependence of the OH
concentration profile was influenced by the sum of the rates of unimolecular
decomposition of syn-CH3CHOO and wall loss. By varying the most relevant
parameters influencing the SCI chemistry in the model and based on the temporal
OH concentration profile, the unimolecular decomposition rate k (293 K) of syn
CH3CHOO was shown to lie within the range 3-30 s(-1), where a value of 20 +/- 10
s(-1) yields the best agreement with the CI chemistry literature.
PMID- 25119644
TI - Stem cell characteristics of dormant cells and cisplatin-induced effects on the
stemness of epithelial ovarian cancer cells.
AB - Tumor dormancy is a common biological property of malignancies and a leading
factor in treatment failure, metastasis and tumor recurrence. The present study
generated mouse xenograft models by injection of PKH26-labeled SKOV3 ovarian
cancer cells, which were divided into two groups: The control group (SKOV3-P
tumors,) and the treatment group that generated resistant tumors following
prolonged administration of cisplatin (SKOV3-R tumors). Administration of
cisplatin resulted in inhibition of the tumor growth and SKOV3-R tumors coexisted
with their host at a stable size. According to fluorochrome PKH26 retention,
there were multiple cell clones (PKH26hi, PKH26low and PKH26neg cells) in the
single cell line generated from xenograft tumors. PKH26hi subsets in SKOV3-P and
SKOV3-R tumors were dormant cells, as the majority were arrested in G0/G1 phase
and expressed high levels of the stem cell markers Oct-4, Nestin, CD117 and CD44.
PKH26hi subsets also demonstrated greater clonogenic capability in vitro and
tumorigenicity in vivo, as compared with PKH26low and PKH26neg cells. Notably,
chemotherapy was demonstrated to lead to the enrichment and enhanced stem-like
characteristics of dormant/slow-cycling PKH26hi cells. The results of the present
study have demonstrated for the first time, to the best of our knowledge, that
dormant tumor cells exhibit stem-like characteristics, and that cisplatin
enhances these characteristics in epithelial ovarian cancer cells.
PMID- 25119646
TI - A novel zinc-finger HIT protein with an additional PAPA-1-like region from Suaeda
liaotungensis K. enhanced transgenic Arabidopsis drought and salt stresses
tolerance.
AB - Zinc-finger HIT belongs to the cross-brace zinc finger protein family and is
involved in the regulation of plant defense and stress responses. In this study,
we cloned a full-length zinc-finger HIT gene (1,377 bp) named SlPAPA1 using
polymerase chain reaction from Suaeda liaotungensis K. and investigated its
function by overexpression in transgenic Arabidopsis. SlPAPA1 contains a zinc
finger HIT domain and a Pim-1-associated protein-1 (PAP-1)-associated protein-1
like (PAPA-1-like) conserved region. Its expression in S. liaotungensis was
induced by drought, high-salt, and cold (4 degrees C) stresses and by abscisic
acid (ABA). Subcellular localization experiments in onion epidermal cells
indicated that SlPAPA1 is localized in the nucleus. Yeast-one hybrid assays
showed that SlPAPA1 functions as a transcriptional activator. SlPAPA1 transgenic
Arabidopsis displayed a higher survival ratio and lower rate of water loss under
drought stress; a higher germination ratio, higher survival ratio, and lower root
inhibition rate under salt stress; and a lower germination ratio and root
inhibition rate under ABA treatment, compared with wild-type Arabidopsis. These
results suggested that SlPAPA1 functions as a stress-responsive zinc-finger HIT
protein involved in the ABA-dependent signaling pathway and may have potential
applications in transgenic breeding to enhance crops abiotic stress tolerances.
PMID- 25119647
TI - Virus-like particles from Escherichia Coli-derived untagged papaya ringspot virus
capsid protein purified by immobilized metal affinity chromatography enhance the
antibody response against a soluble antigen.
AB - There is a growing interest in using virus-like particles (VLPs) as scaffolds for
the presentation of antigens of choice to the immune system. In this work, VLPs
from papaya ringspot virus capsid protein expressed in Escherichia coli were
evaluated as enhancers of antibody response against a soluble antigen.
Interestingly, although the capsid protein lacks a histidine tag, its
purification by immobilized metal affinity chromatography was achieved. The
formation of VLPs was demonstrated by electron microscopy for the first time for
this capsid protein. VLPs were enriched by polyethylene glycol precipitation.
Additionally, these VLPs were chemically coupled to green fluorescent protein in
order to evaluate them as antigen carriers; however, bioconjugate instability was
observed. Nonetheless, the adjuvant effect of these VLPs on BALB/c mice was
evaluated, using GFP as antigen, resulting in a significant increase in anti-GFP
IgG response, particularly, IgG1 class, demonstrating that the VLPs enhance the
immune response against the antigen chosen in this study.
PMID- 25119649
TI - Approaches to the total synthesis of chaetochalasin A.
AB - Chaetochalasin A is a complex natural product whose biosynthesis may involve two
domino Diels-Alder reactions. Approaches to the total synthesis of chaetochalasin
A using this approach have been studied. Methyl (6R,8S,2Z,4E,10E,12E,14E)
6,8,10,14-tetramethylhexadeca-2,4,10,12,14-pentaenoate was identified as a key
intermediate and was synthesized from (E)-1-bromo-4-tert-butyldimethylsilyloxy-2
methylbut-2-ene using diastereoselective alkylations of derivatives of (+)
pseudoephedrine to introduce the stereogenic centres, a modified Julia reaction
to prepare the conjugated triene and a phosphonate condensation to provide the
(2Z)-alkene. However, during the synthesis, facile geometrical isomerisation of
the (14E)-trisubstituted and (2Z)-double-bonds was observed and attempts to
incorporate this pentaene into a synthesis of chaetochalasin A led to the
formation of mixtures of products. The analogous ethyl 6,8,10,14
tetramethylhexadeca-4,10,12,14-tetraenoate [that lacks the (2Z)-double-bond] was
incorporated into a Diels-Alder precursor by acylation of a valine-derived N
acylpyrrolidinone followed by oxidative elimination of the corresponding 3
(phenylselanyl)pyrrolidinone. However, preliminary studies of the macrocycle
forming Diels-Alder reaction for a synthesis of chaetochalasin A were complicated
by (E,Z)-isomerisation of the (10E)-double-bond of the conjugated triene and
three Diels-Alder adducts were isolated and characterised. Further studies of
this approach to chaetochalasin A will require an alternative procedure for the
generation of the acylpyrrolinone in the presence of the acid sensitive
conjugated triene.
PMID- 25119648
TI - Matrix-assisted refolding, purification and activity assessment using a 'form
invariant' assay for matrix metalloproteinase 2 (MMP2).
AB - Matrix metalloproteinases expression is used as biomarker for various cancers and
associated malignancies. Since these proteinases can cleave many intracellular
proteins, overexpression tends to be toxic; hence, a challenge to purify them. To
overcome these limitations, we designed a protocol where full length pro-MMP2
enzyme was overexpressed in E. coli as inclusion bodies and purified using 6xHis
affinity chromatography under denaturing conditions. In one step, the enzyme was
purified and refolded directly on the affinity matrix under redox conditions to
obtain a bioactive protein. The pro-MMP2 protein was characterized by mass
spectrometry, CD spectroscopy, zymography and activity analysis using a simple in
house developed 'form invariant' assay, which reports the total MMP2 activity
independent of its various forms. The methodology yielded higher yields of
bioactive protein compared to other strategies reported till date, and we
anticipate that using the protocol, other toxic proteins can also be
overexpressed and purified from E. coli and subsequently refolded into active
form using a one step renaturation protocol.
PMID- 25119650
TI - Kinetics of 3-nitrotyrosine modification on exposure to hypochlorous acid.
AB - The markers 3-nitrotyrosine and 3-chlorotyrosine are measured as surrogates for
reactive nitrogen species and hypochlorous acid respectively, which are both
elevated in inflamed human tissues. Previous studies reported a loss of 3
nitrotyrosine when exposed to hypochlorous acid, suggesting that observations of
3-nitrotyrosine underestimate the presence of reactive nitrogen species in
diseased tissue (Whiteman and Halliwell, Biochemical and Biophysical Research
Communications, 258, 168-172 (1999)). This report evaluates the significance of 3
nitrotyrosine loss by measuring the kinetics of the reaction between 3
nitrotyrosine and hypochlorous acid. The results demonstrate that 3-nitrotyrosine
is chlorinated by hypochlorous acid or chloramines to form 3-chloro-5
nitrotyrosine. As 3-nitrotyrosine from in vivo samples is usually found within
proteins rather than as free amino acid, we also examined the reaction of 3
nitrotyrosine modification in the context of peptides. The chlorination of 3
nitrotyrosine in peptides was observed to occur up to 700-fold faster than
control reactions using equivalent amino acid mixtures. These results further
advance our understanding of tyrosine chlorination and the use of 3-nitrotyrosine
formed in vivo as a biomarker of reactive nitrogen species.
PMID- 25119651
TI - miR-195/497 induce postnatal quiescence of skeletal muscle stem cells.
AB - Skeletal muscle stem cells (MuSCs), the major source for skeletal muscle
regeneration in vertebrates, are in a state of cell cycle arrest in adult
skeletal muscles. Prior evidence suggests that embryonic muscle progenitors
proliferate and differentiate to form myofibres and also self-renew, implying
that MuSCs, derived from these cells, acquire quiescence later during
development. Depletion of Dicer in adult MuSCs promoted their exit from
quiescence, suggesting microRNAs are involved in the maintenance of quiescence.
Here we identified miR-195 and miR-497 that induce cell cycle arrest by targeting
cell cycle genes, Cdc25 and Ccnd. Reduced expression of MyoD in juvenile MuSCs,
as a result of overexpressed miR-195/497 or attenuated Cdc25/Ccnd, revealed an
intimate link between quiescence and suppression of myogenesis in MuSCs.
Transplantation of cultured MuSCs treated with miR-195/497 contributed more
efficiently to regenerating muscles of dystrophin-deficient mice, indicating the
potential utility of miR-195/497 for stem cell therapies.
PMID- 25119652
TI - Factors Affecting Caregiver Burden 1 Year After Severe Traumatic Brain Injury: A
Prospective Nationwide Multicenter Study.
AB - OBJECTIVES: To assess burden in the caregivers of patients with severe traumatic
brain injury (TBI) 1 year postinjury, related to caregiver's demographic data and
social network, patient's demographic data, injury severity, and functional
status. DESIGN: Prospective national multicenter study. Self-report from
caregivers, patient data collected from the national cohort on patients with
severe TBI. PARTICIPANTS: 92 caregivers. MAIN OUTCOME MEASURE: The Caregiver
Burden Scale (CBS). RESULTS: Total caregiver burden was reported high in 16% of
caregivers and moderate in 34%. The mean total burden index was 2.12, indicating
a moderate burden. Caregivers reported highest scores on the General strain
index, followed by the Disappointment index. Poor social network, feeling
loneliness, and caring for patients with severe disability were significant
predictors of higher burden in univariate analyses (P < .01). Multiple linear
regression analyses showed that experiencing loneliness and caring for a patient
with more severe disability were independent predictors for higher caregiver
burden for all CBS indices. Marital status (married) and low frequency of meeting
friends were significant results in some indices. CONCLUSIONS: Lack of a social
network, feeling loneliness, and patient's functional status are predictors of
caregiver burden. General strain, disappointment, and isolation were identified
as areas in which caregiver burden is high.
PMID- 25119653
TI - Trajectories of Sleep and Its Predictors in the First Year Following Traumatic
Brain Injury.
AB - OBJECTIVES: To examine how sleep patterns change over the first year following
traumatic brain injury (TBI) and to determine whether specific demographic and
disease characteristics predict the trajectories of sleep. DESIGN: Prospective
study. PARTICIPANTS: Fifty-three patients with first-ever mild to severe TBI.
MAIN MEASUREMENTS: Sleep measured by actigraphy for 7 consecutive days in the
first, third, sixth, and twelfth months following TBI: Chinese versions of Beck
Anxiety Inventory and Beck Depression Inventory-II (CBDI-II) measured at the same
time points. Data were analyzed with a linear mixed model. RESULTS: Sleep
efficiency (the ratio of sleep time to the total time spent in bed) showed a
significant upward trend during the study period. Scores on the Chinese version
of the Beck Anxiety Inventory and the CBDI-II as well as the use of analgesics
significantly predicted the slope of change in sleep efficiency over time.
CONCLUSIONS: Poor sleep efficiency is a common symptom in the first year among
patients with first-ever TBI. Healthcare providers should consider both mental
health and pain issues when dealing with sleep complaints in patients with TBI.
PMID- 25119655
TI - Preferential adsorption behavior of methylene blue dye onto surface hydroxyl
group enriched TiO2 nanotube and its photocatalytic regeneration.
AB - The present manuscript focus on the synthesis of surface hydroxyl group enriched
titanium dioxide nanotube (TNT) by hydrothermal method for preferential
adsorption of methylene blue (MB) dye. The mixture of methylene blue (MB) and
rhodamine B (RhB) dye was used to study the preferential adsorption nature of
TNT. The synthesized TNT were characterized by various techniques such as powder
X-ray diffraction (PXRD), scanning electron microscopy (SEM), transmission
electron microscopy (TEM), N2 adsorption, and ammonia-temperature programmed
desorption (NH3-TPD) analysis. Result demonstrated that enhancement in the
surface area of TNT and higher number of hydroxyl group on the surface of TNT. In
the binary mixture, the adsorption of MB dye was 12.9 times higher as compared to
RhB dye, which clearly indicated the preferential adsorption of MB dye on TNT
surface. The preferential interaction of MB on TNT is due to the electrostatic
interaction between the cationic MB and negatively charged TNT surface. The
preferential adsorption of MB dye was studied by applying Langmuir, Freundlich
and Sips isotherm; pseudo-first and second-order kinetic model. Furthermore, the
regeneration of dye adsorbed TNT was carried out by eco-friendly photocatalytic
process under the irradiation of ultraviolet light.
PMID- 25119654
TI - Association of alcohol drinking with verbal and visuospatial memory impairment in
older adults: Clinical Research Center for Dementia of South Korea (CREDOS)
study.
AB - BACKGROUND: The study's aim was to examine the association of alcohol consumption
with verbal and visuospatial memory impairment in older people. METHODS:
Participants were 1,572, aged >=60 years, in the hospital-based registry of the
Clinical Research Center for Dementia of South Korea (CREDOS). Moderate drinking
was defined as no more than seven drinks per week and three drinks per day.
Memory impairment was defined as performance with more than 1 standard deviation
below the mean value on the Seoul Verbal Learning Test and Rey Complex Figure
Test. RESULTS: Those who consumed alcohol moderately, compared with abstainers,
had a lower odds of verbal memory impairment (Odds Ratio [OR] = 0.64; 95%
Confidence Interval [CI]: 0.46-0.87), adjusting for covariates. Visuospatial
memory, however, was not significantly associated with alcohol consumption.
CONCLUSIONS: Moderate alcohol drinking is associated with a reduced likelihood of
verbal memory impairment among older people attending memory clinics.
PMID- 25119657
TI - Contact electrification field-effect transistor.
AB - Utilizing the coupled metal oxide semiconductor field-effect transistor and
triboelectric nanogenerator, we demonstrate an external force
triggered/controlled contact electrification field-effect transistor (CE-FET), in
which an electrostatic potential across the gate and source is created by a
vertical contact electrification between the gate material and a "foreign"
object, and the carrier transport between drain and source can be
tuned/controlled by the contact-induced electrostatic potential instead of the
traditional gate voltage. With the two contacted frictional layers vertically
separated by 80 MUm, the drain current is decreased from 13.4 to 1.9 MUA in
depletion mode and increased from 2.4 to 12.1 MUA in enhancement mode at a drain
voltage of 5 V. Compared with the piezotronic devices that are controlled by the
strain-induced piezoelectric polarization charged at an interface/junction, the
CE-FET has greatly expanded the sensing range and choices of materials in
conjunction with semiconductors. The CE-FET is likely to have important
applications in sensors, human-silicon technology interfacing, MEMS,
nanorobotics, and active flexible electronics. Based on the basic principle of
the CE-FET, a field of tribotronics is proposed for devices fabricated using the
electrostatic potential created by triboelectrification as a "gate" voltage to
tune/control charge carrier transport in conventional semiconductor devices. By
the three-way coupling among triboelectricity, semiconductor, and
photoexcitation, plenty of potentially important research fields are expected to
be explored in the near future.
PMID- 25119656
TI - Postoperative radioactive iodine administration for differentiated thyroid cancer
patients.
AB - PURPOSE OF REVIEW: Radioactive iodine (RAI) is administered postoperatively to
the majority of thyroid cancer patients. No available study has demonstrated any
benefit in low-risk patients. RECENT FINDINGS: RAI should be used selectively in
low and intermediate-risk patients, based on the surgical and pathological
reports and on postoperative serum thyroglobulin level and neck ultrasonography.
When used, a low activity (30 mCi) is administered following recombinant human
thyrotropin stimulation. High-risk patients are treated with a high activity of
RAI (100 mCi or more). SUMMARY: RAI is not administered in many low-risk patients
who can be reliably followed up with serum thyroglobulin determination on L
thyroxine treatment and neck ultrasonography. RAI may be administered in case of
abnormality, and this delay will not reduce the chance of cure.
PMID- 25119658
TI - Dynamics of the DNA repair proteins WRN and BLM in the nucleoplasm and nucleoli.
AB - We have investigated the mobility of two EGFP-tagged DNA repair proteins, WRN and
BLM. In particular, we focused on the dynamics in two locations, the nucleoli and
the nucleoplasm. We found that both WRN and BLM use a "DNA-scanning" mechanism,
with rapid binding-unbinding to DNA resulting in effective diffusion. In the
nucleoplasm WRN and BLM have effective diffusion coefficients of 1.62 and 1.34
MUm(2)/s, respectively. Likewise, the dynamics in the nucleoli are also best
described by effective diffusion, but with diffusion coefficients a factor of ten
lower than in the nucleoplasm. From this large reduction in diffusion coefficient
we were able to classify WRN and BLM as DNA damage scanners. In addition to WRN
and BLM we also classified other DNA damage proteins and found they all fall into
one of two categories. Either they are scanners, similar to WRN and BLM, with
very low diffusion coefficients, suggesting a scanning mechanism, or they are
almost freely diffusing, suggesting that they interact with DNA only after
initiation of a DNA damage response.
PMID- 25119661
TI - Applicability domain based on ensemble learning in classification and regression
analyses.
AB - We discuss applicability domains (ADs) based on ensemble learning in
classification and regression analyses. In regression analysis, the AD can be
appropriately set, although attention needs to be paid to the bias of the
predicted values. However, because the AD set in classification analysis is too
wide, we propose an AD based on ensemble learning and data density. First, we set
a threshold for data density below which the prediction result of new data is not
reliable. Then, only for new data with a data density higher than the threshold,
we consider the reliability of the prediction result based on ensemble learning.
By analyzing data from numerical simulations and quantitative structural
relationships, we validate our discussion of ADs in classification and regression
analyses and confirm that appropriate ADs can be set using the proposed method.
PMID- 25119660
TI - MicroRNA-449 suppresses proliferation of hepatoma cell lines through blockade
lipid metabolic pathway related to SIRT1.
AB - MicroRNA (miRNA or miR) inhibition of oncogenic related pathways has been shown
to be a promising therapeutic approach for cancer. SIRT1 might be a promoter
factor on tumorigenesis of hepatocellular carcinoma (HCC). However, the mechanism
is unknown. We investigated whether miRNAs regulate the SIRT1 and its downstream
SREBP-lipogenesis-cholesterogenesis metabolic pathway in hepatoma cells. Human
hepatoma cells were transfected with miR-449 mimics and inhibitors, and the
effects of miR-449 on cell proliferation was assessed. We identified the miRNAs,
miR-449, that control lipogenesis and cholesterogenesis in hepatoma cells by
inhibiting SIRT1 and SREBP-1c expression and downregulating their targeted genes,
including fatty acid synthase (FASN) and 3-hydroxy-3-methylglutaryl CoA reductase
(HMGCR). MiR-449 repressed DNA synthesis, mitotic entry and proliferation of
hepatoma cells. Restoration of miR-449 led to suppression of SIRT1 expression and
liver tumorigenesis. The newly identified miRNAs, miR-449 represents a novel
targeting mechanism for HCC therapy.
PMID- 25119662
TI - Redox and photoinduced electron-transfer properties in short distance organoboryl
ferrocene-subphthalocyanine dyads.
AB - Reaction between ferrocene lithium or ethynylferrocene magnesium bromide and
(chloro)boronsubphthalocyanine leads to formation of ferrocene- (2) and
ethynylferrocene- (3) containing subphthalocyanine dyads with a direct
organometallic B-C bond. New donor-acceptor dyads were characterized using UV-vis
and magnetic circular dichroism (MCD) spectroscopies, NMR method, and X-ray
crystallography. Redox potentials of the rigid donor-acceptor dyads 2 and 3 were
studied using the cyclic voltammetry (CV) and differential pulse voltammetry
(DPV) approaches and compared to the parent subphthalocyanine 1 and
conformationally flexible subphthalocyanine ferrocenenylmethoxide (4) and
ferrocenyl carboxylate (5) dyads reported earlier. It was found that the first
oxidation process in dyads 2 and 3 is ferrocene-centered, while the first
reduction as well as the second oxidation are centered at the subphthalocyanine
ligand. Density functional theory-polarized continuum model (DFT-PCM) and time
dependent (TD) DFT-PCM methods were used to probe the electronic structures and
explain the UV-vis and MCD spectra of complexes 1-5. DFT-PCM calculations suggest
that the LUMO, LUMO+1, and HOMO-3 in new dyads 2 and 3 are centered at the
subphthalocyanine ligand, while the HOMO to HOMO-2 in both dyads are
predominantly ferrocene-centered. TDDFT-PCM calculations on compounds 1-5 are
indicative of the pi -> pi* transitions dominance in their UV-vis spectra, which
is consistent with the experimental data. The excited state dynamics of the
parent subphthalocyanine 1 and dyads 2-5 were investigated using time-resolved
transient spectroscopy. In the dyads 2-5, the initially excited state is rapidly
(<2 ps) quenched by electron transfer from the ferrocene ligand. The lifetime of
the charge transfer state demonstrates a systematic dependence on the structure
of the bridge between the subphthalocyanine and ferrocene.
PMID- 25119659
TI - Systemic administration of erythropoietin inhibits retinopathy in RCS rats.
AB - OBJECTIVE: Royal College of Surgeons (RCS) rats develop vasculopathy as
photoreceptors degenerate. The aim of this study was to examine the effect of
erythropoietin (EPO) on retinopathy in RCS rats. METHODS: Fluorescein angiography
was used to monitor retinal vascular changes over time. Changes in retinal glia
and vasculature were studied by immunostaining. To study the effects of EPO on
retinal pathology, EPO (5000 IU/kg) was injected intraperitoneally in 14 week old
normal and RCS rats twice a week for 4 weeks. Changes in the retinal vasculature,
glia and microglia, photoreceptor apoptosis, differential expression of p75
neurotrophin receptor (p75NTR), pro-neurotrophin 3 (pro-NT3), tumour necrosis
factor-alpha (TNFalpha), pigment epithelium derived factor (PEDF) and vascular
endothelial growth factor-A (VEGF-A), the production of CD34(+) cells and
mobilization of CD34(+)/VEGF-R2(+) cells as well as recruitment of CD34(+) cells
into the retina were examined after EPO treatment. RESULTS: RCS rats developed
progressive capillary dropout and subretinal neovascularization which were
accompanied by retinal gliosis. Systemic administration of EPO stabilized the
retinal vasculature and inhibited the development of focal vascular lesions.
Further studies showed that EPO modulated retinal gliosis, attenuated
photoreceptor apoptosis and p75NTR and pro-NT3 upregulation, promoted the
infiltration of ramified microglia and stimulated VEGF-A expression but had
little effect on TNFalpha and PEDF expression. EPO stimulated the production of
red and white blood cells and CD34(+) cells along with effective mobilization of
CD34(+)/VEGF-R2(+) cells. Immunofluorescence study demonstrated that EPO enhanced
the recruitment of CD34+ cells into the retina. CONCLUSIONS: Our results suggest
that EPO has therapeutic potentials in treatment of neuronal and vascular
pathology in retinal disease. The protective effects of EPO on photoreceptors and
the retinal vasculature may involve multiple mechanisms including regulation of
retinal glia and microglia, inhibition of p75NTR-pro-NT3 signaling together with
stimulation of production and mobilization of bone marrow derived cells.
PMID- 25119663
TI - Substrate positioning by Gln(239) stimulates turnover in factor inhibiting HIF,
an alphaKG-dependent hydroxylase.
AB - Nonheme Fe(II)/alphaKG-dependent oxygenases catalyze diverse reactions, typically
inserting an O atom from O2 into a C-H bond. Although the key to their catalytic
cycle is the fact that binding and positioning of primary substrate precede O2
activation, the means by which substrate binding stimulates turnover is not well
understood. Factor Inhibiting HIF (FIH) is a Fe(II)/alphaKG-dependent oxygenase
that acts as a cellular oxygen sensor in humans by hydroxylating the target
residue Asn(803), found in the C-terminal transactivation domain (CTAD) of
hypoxia inducible factor-1. FIH-Gln(239) makes two hydrogen bonds with CTAD
Asn(803), positioning this target residue over the Fe(II). We hypothesized the
positioning of the side chain of CTAD-Asn(803) by FIH-Gln(239) was critical for
stimulating O2 activation and subsequent substrate hydroxylation. The steady
state characterization of five FIH-Gln(239) variants (Ala, Asn, Glu, His, and
Leu) tested the role of hydrogen bonding potential and sterics near the target
residue. Each variant exhibited a 20-1200-fold decrease in kcat and
kcat/KM(CTAD), but no change in KM(CTAD), indicating that the step after CTAD
binding was affected by point mutation. Uncoupled O2 activation was prominent in
these variants, as shown by large coupling ratios (C = [succinate]/[CTAD-OH] = 3
5) for each of the FIH-Gln(239) -> X variants. The coupling ratios decreased in
D2O, indicating an isotope-sensitive inactivation for variants, not observed in
the wild type. The data presented indicate that the proper positioning of CTAD
Asn(803) by FIH-Gln(239) is necessary to suppress uncoupled turnover and to
support substrate hydroxylation, suggesting substrate positioning may be crucial
for directing O2 reactivity within the broader class of alphaKG hydroxylases.
PMID- 25119667
TI - A high-protein formula increases colonic peptide transporter 1 activity during
neonatal life in low-birth-weight piglets and disturbs barrier function later in
life.
AB - Dietary peptides are absorbed along the intestine through peptide transporter 1
(PepT-1) which is highly responsive to dietary protein level. PepT-1 is also
involved in gut homeostasis, both initiating and resolving inflammation. Low
birth-weight (LBW) neonates are routinely fed a high-protein (HP) formula to
enhance growth. However, the influence of this nutritional practice on PepT-1
activity is unknown. Intestinal PepT-1 activity was compared in normal-birth
weight (NBW) and LBW piglets. The effect of HP v. normal-protein (NP) formula
feeding on PepT-1 activity and gut homeostasis in LBW piglets was evaluated,
during the neonatal period and in adulthood. Flux of cephalexin (CFX) across the
tissue mounted in Ussing chambers was used as an indicator of PepT-1 activity.
CFX flux was greater in the ileum, but not jejunum or colon, of LBW than NBW
piglets during the neonatal period. When LBW piglets were formula-fed, the HP
formula increased colonic CFX during the 1st week of life. Later in life,
intestinal CFX fluxes and barrier function were similar whether LBW pigs had been
fed NP or HP formula. However, colonic permeability of HP- but not NP-fed pigs
increased when luminal pH was brought to 6.0. The formyl peptide N-formyl
methionyl-leucyl-phenylalanine conferred colonic barrier protection in HP-fed
piglets. Heat shock protein 27 levels in the colonic mucosa of HP-fed LBW pigs
correlated with the magnitude of response to the acidic challenge. In conclusion,
feeding a HP formula enhanced colonic PepT-1 activity in LBW pig neonates and
increased sensitivity of the colon to luminal stress in adulthood.
PMID- 25119668
TI - Micro-segmented flow and multisensor-technology for microbial activity profiling.
AB - The combination of micro-segmented flow with miniaturized flow-through
multisensor-technology has been utilized for metabolite profiling of soil
bacteria. Series of sub-MUl segments were generated containing soil sample slurry
from historic copper mining sites and exposed to heavy metal salts of copper and
nickel. Segments were examined for bacterial growth and spectral properties as
well as for the effect of heavy metal-treatment after different incubation times.
In order to evaluate microbial growth, extinction was recorded with 4 different
spectral channels. Fluorescence was measured using a microflow-through
fluorometer to detect both growth and production of fluorescent dyes or
metabolites. The incidence of single segments with enhanced absorption in one of
the spectral channels or enhanced fluorescence was scored to detect soil
microorganisms with interesting properties for further screening. The study could
show that the number of vegetated segments, the density of microorganisms in the
segments after cultivation and the spectral response are different for separate
soil samples and different metals. Thus, the highly parallelized and miniaturized
segmented flow method is a promising tool for profiling of soil samples with
regard to identifying micro-organisms with interesting profiles for secondary
metabolite-production.
PMID- 25119665
TI - Multi-level factors affecting entry into and engagement in the HIV continuum of
care in Iringa, Tanzania.
AB - Progression through the HIV continuum of care, from HIV testing to lifelong
retention in antiretroviral therapy (ART) care and treatment programs, is
critical to the success of HIV treatment and prevention efforts. However,
significant losses occur at each stage of the continuum and little is known about
contextual factors contributing to disengagement at these stages. This study
sought to explore multi-level barriers and facilitators influencing entry into
and engagement in the continuum of care in Iringa, Tanzania. We used a mixed
methods study design including facility-based assessments and interviews with
providers and clients of HIV testing and treatment services; interviews, focus
group discussions and observations with community-based providers and clients of
HIV care and support services; and longitudinal interviews with men and women
living with HIV to understand their trajectories in care. Data were analyzed
using narrative analysis to identify key themes across levels and stages in the
continuum of care. Participants identified multiple compounding barriers to
progression through the continuum of care at the individual, facility, community
and structural levels. Key barriers included the reluctance to engage in HIV
services while healthy, rigid clinic policies, disrespectful treatment from
service providers, stock-outs of supplies, stigma and discrimination, alternate
healing systems, distance to health facilities and poverty. Social support from
family, friends or support groups, home-based care providers, income generating
opportunities and community mobilization activities facilitated engagement
throughout the HIV continuum. Findings highlight the complex, multi-dimensional
dynamics that individuals experience throughout the continuum of care and
underscore the importance of a holistic and multi-level perspective to understand
this process. Addressing barriers at each level is important to promoting
increased engagement throughout the continuum.
PMID- 25119664
TI - Membrane interacting regions of Dengue virus NS2A protein.
AB - The Dengue virus (DENV) NS2A protein, essential for viral replication, is a
poorly characterized membrane protein. NS2A displays both protein/protein and
membrane/protein interactions, yet neither its functions in the viral cycle nor
its active regions are known with certainty. To highlight the different membrane
active regions of NS2A, we characterized the effects of peptides derived from a
peptide library encompassing this protein's full length on different membranes by
measuring their membrane leakage induction and modulation of lipid phase
behavior. Following this initial screening, one region, peptide dens25, had
interesting effects on membranes; therefore, we sought to thoroughly characterize
this region's interaction with membranes. This peptide presents an
interfacial/hydrophobic pattern characteristic of a membrane-proximal segment. We
show that dens25 strongly interacts with membranes that contain a large
proportion of lipid molecules with a formal negative charge, and that this effect
has a major electrostatic contribution. Considering its membrane modulating
capabilities, this region might be involved in membrane rearrangements and thus
be important for the viral cycle.
PMID- 25119669
TI - High seroprevalence of human herpesvirus type 8 infection in males with advanced
lung carcinoma.
AB - Human herpesvirus type 8 (HHV-8) DNA is consistently found in all types of
Kaposi's sarcoma, which is prevalent in immunocompromised patients. Patients with
advanced lung carcinoma often showed immunologic abnormalities, and prevalence of
HHV-8 infection is unclear. In this study, blood samples from 109 lung carcinoma
patients and 109 age- and sex-matched healthy controls were analyzed for
lymphocyte and monocyte counts, and for antibody, DNA, and genotype of HHV-8.
Lung carcinoma patients had significantly lower lymphocyte and higher monocyte
counts than healthy controls (p < 0.0001, both). HHV-8 seropositivity was more
prevalent in lung carcinoma patients (41.3%), particularly in male patients
(50.8%), than in controls (24.8%) (p = 0.01 and 0.002, respectively). The
seropositivity was also significantly higher in male (50.8%) than female patients
(27.3%, p = 0.01). Titers of HHV-8 antibody in patients also significantly
exceeded those in controls (p = 0.004). Under a higher threshold (antibody titer
>=1:160) which is equivalent to that of enzyme-linked immunosorbent assay, lung
carcinoma patients still had higher HHV-8 seropositivity than controls (p =
0.006). Three patients with stage IV lung carcinoma were positive for HHV-8 DNA
with K1 gene subtype C3, D1, and E, respectively; they had much lower lymphocyte
counts (658 +/- 132 uL) than patients positive for HHV-8 antibodies only (1,449
+/- 873 uL). The study indicates that lung carcinoma patients, particularly
males, have a high seroprevalence of HHV-8. HHV-8 DNA detected in the patients
with advanced lung carcinoma may be a result of virus reactivation in the
immunocompromised status.
PMID- 25119671
TI - The Au(I) catalyzed activation of allenamides and their subsequent transformation
into chromanes: a method for the regiocontrolled addition to the alpha- and gamma
positions of the allene unit.
AB - Au(I) activation of allenamides in the presence of phenols leads to the formation
of chromanes in moderate to good yields. This catalytic process is dependent on
the counterion which facilitates the activation of the in situ formed imine.
Furthermore, this iminium can be intercepted by trimethylallyl silane, via the
Hosomi-Sakurai reaction, giving a formal procedure for the regioselective
intermolecular addition of two carbon nucleophiles to an allenamide at the alpha-
and gamma-positions.
PMID- 25119670
TI - Vaccination with Streptococcus pyogenes nuclease A stimulates a high antibody
response but no protective immunity in a mouse model of infection.
AB - Streptococcus pyogenes is a human pathogen which causes a spectrum of diseases
ranging from pharyngitis to rheumatic fever, necrotising fasciitis and toxic
shock syndrome. Development of a vaccine for S. pyogenes has been confounded both
by the diversity of the disease-causing serotypes and the spectre of
inadvertently stimulating autoimmunity. The S. pyogenes nuclease A (SpnA) is a
recently characterised virulence factor that is highly conserved across strains
and expressed during human disease. Deletion of spnA from S. pyogenes results in
reduced survival of bacteria in whole human blood and attenuated virulence in a
mouse model of infection. Collectively these features suggest that SpnA has
potential as a vaccine candidate for S. pyogenes. Mice vaccinated subcutaneously
with single or multiple doses of recombinant SpnA emulsified in Incomplete
Freund's Adjuvant developed a robust and durable IgG response, including
neutralising activity, to this protein. However, vaccination with rSpnA conferred
no advantage in terms of lesion development, disease symptoms or colonisation
levels after a sub-lethal subcutaneous challenge with S. pyogenes. Anti-SpnA
serum IgG responses and neutralising activity were increased in response to
challenge, indicating that SpnA is expressed in vivo. SpnA is unlikely to be a
suitable antigen for a vaccine against S. pyogenes.
PMID- 25119672
TI - Roles of Ebp2 and ribosomal protein L36 in ribosome biogenesis in Saccharomyces
cerevisiae.
AB - Ebp2 plays an essential role in biogenesis of 60S ribosomal subunits. We
determined the genetic interactions between EBP2 and RPL36A/B, which encodes
ribosomal protein L36a/b. RPL36A/B was a multicopy suppressor to ebp2 mutants,
and the suppression was not common to defects in ribosome biogenesis resulting
from other mutations of assembly factors. Disruption of RPL36A or RPL36B caused
synthetic enhancement of the growth defect of the ebp2-14 allele at high
temperatures. Disruption of RPL36B led to a more severe growth defect than that
of RPL36A due to imbalances in the expression levels of the duplicated genes.
Primer-extension analysis revealed that L36a/b is required for the processing of
27SA2, 27SA3, and 27SBL pre-rRNAs. Two-hybrid analysis indicated that Ebp2
interacts with ribosomal proteins L36a/b, L34a/b, and L8, which in mature
ribosomes are located adjacent to each other in close proximity to the 3' end of
5.8S rRNA. These results suggest that Ebp2 functions cooperatively with ribosomal
proteins L36, L34, and L8 in biogenesis of the 60S ribosomal subunit.
PMID- 25119674
TI - Rapid development of proteomics in China: from the perspective of the Human Liver
Proteome Project and technology development.
AB - Proteomics focuses on the systematic identification and quantification of entire
proteomes and interpretation of proteins' biological functions. During the last
decade, proteomics in China has grown much faster than other research fields in
the life sciences. At the beginning of the second decade of the 21(st) century,
the rapid development of high-resolution and high-speed mass spectrometry makes
proteomics a powerful tool to study the mechanisms underlying
physiological/pathological processes in organisms. This article provides a brief
overview of proteomics technology development and representative scientific
progress of the Human Liver Proteome Project (HLPP) in China over the past three
years.
PMID- 25119673
TI - Tetracaine, a local anesthetic, preferentially induces translational inhibition
with processing body formation rather than phosphorylation of eIF2alpha in yeast.
AB - It is unclear whether local anesthetics, such as tetracaine, and antipsychotics,
such as phenothiazines, act on lipids or proteins. In Saccharomyces cerevisiae,
these drugs inhibit growth, translation initiation, and actin polarization, and
induce cell lysis at high concentrations. These activities are likely due to the
cationic amphiphilic structure common to these agents. Although drug-induced
translational inhibition is conserved in mammalian cells, other mechanisms,
including the phosphorylation of eIF2alpha, a eukaryotic translational initiation
factor, remain poorly understood. At a concentration of 10 mM, tetracaine rapidly
inhibited translation initiation and lysed cells, whereas, at 2.5 mM, it slowly
induced inhibition without lysis. The pat1 disruptant defective in mRNA decapping
and the xrn1 disruptant defective in 5'-3' exoribonuclease were partially
resistant to translational inhibition by tetracaine at each concentration, but
the gcn2 disruptant defective in the eIF2alpha kinase was not. Phosphorylation of
eIF2alpha was induced by 10 mM but not by 2.5 mM tetracaine, whereas processing
bodies (P-bodies) were formed at 2.5 mM in Pat1-dependent and -independent
manners. Therefore, administration of tetracaine inhibits translation initiation
with P-body formation at both concentrations but acts via the Gcn2-eIF2alpha
system only at the higher concentration. Because other local anesthetics and
phenothiazines induced Pat1-dependent P-body formation, the mechanisms involved
in translational inhibition by these cationic amphiphiles are similar. These
results suggest that this dose-dependent biphasic translational inhibition by
tetracaine results from an increase in membrane proteins that are indirectly
inhibited by nonspecific interactions of cationic amphiphiles with membrane
lipids.
PMID- 25119675
TI - Pathogenesis of a Chinese strain of bovine adenovirus type 3 infection in albino
guinea pigs.
AB - Bovine adenovirus type 3 (BAV-3) is considered one of the most important
respiratory tract agents of cattle and is widespread among cattle around the
world. A BAV-3 strain was isolated from a bovine nasal swab for the first time in
China in 2009 and named HLJ0955. Subsequently, BAV-3 has frequently been isolated
from calves with respiratory diseases in China. To date, only limited study on
the pathogenesis of BAV-3 infection in cotton rats has been conducted, and the
pathogenesis of BAV-3 infection in guinea pigs has not been reported. Therefore,
sixteen albino guinea pigs were inoculated intranasally with HLJ0955. All of the
infected guinea pigs had apparently elevated rectal temperatures (39.2 degrees C
39.9 degrees C) at 2-7 days post-inoculation (PI). Consolidation and petechial
hemorrhage were also observed in guinea pigs experimentally infected with
HLJ0955. Viral replication was detectable by virus isolation and titration and by
immunohistochemistry in the lungs of guinea pigs as early as 24 h PI. Viral DNA
was detectable in the lungs of infected guinea pigs during 11 days of observation
by real-time PCR. Virus-neutralizing antibodies against BAV-3 were detectable
from 11 days PI and reached a peak titer at 15 days PI. Histopathological changes
mainly occurred in the lungs of infected guinea pigs and were characterized by
thickening of alveolar septa, mononuclear cell infiltration, hemorrhage and
alveolar epithelial necrosis. These results indicate that HLJ0955 can replicate
in the lungs of guinea pigs and cause fever and gross and histological lesions.
The guinea pig infection model of BAV-3 would serve as a useful system for
monitoring the infection process and pathogenesis of the Chinese BAV-3 strain
HLJ0955, as well as immune responses to BAV-3 vaccines.
PMID- 25119676
TI - Improvements to pairwise sequence comparison (PASC): a genome-based web tool for
virus classification.
AB - The number of viral genome sequences in the public databases is increasing
dramatically, and these sequences are playing an important role in virus
classification. Pairwise sequence comparison is a sequence-based virus
classification method. A program using this method calculates the pairwise
identities of virus sequences within a virus family and displays their
distribution, and visual analysis helps to determine demarcations at different
taxonomic levels such as strain, species, genus and subfamily. Subsequent
comparison of new sequences against existing ones allows viruses from which the
new sequences were derived to be classified. Although this method cannot be used
as the only criterion for virus classification in some cases, it is a
quantitative method and has many advantages over conventional virus
classification methods. It has been applied to several virus families, and there
is an increasing interest in using this method for other virus families/groups.
The Pairwise Sequence Comparison (PASC) classification tool was created at the
National Center for Biotechnology Information. The tool's database stores
pairwise identities for complete genomes/segments of 56 virus families/groups.
Data in the system are updated every day to reflect changes in virus taxonomy and
additions of new virus sequences to the public database. The web interface of the
tool ( http://www.ncbi.nlm.nih.gov/sutils/pasc/ ) makes it easy to navigate and
perform analyses. Multiple new viral genome sequences can be tested
simultaneously with this system to suggest the taxonomic position of virus
isolates in a specific family. PASC eliminates potential discrepancies in the
results caused by different algorithms and/or different data used by researchers.
PMID- 25119677
TI - A novel combination of a new umbravirus, a new satellite RNA and potato leafroll
virus causes tobacco bushy top disease in Ethiopia.
AB - Etiological studies of a recently emerged bushy top disease of tobacco in
Ethiopia indicated that a ~4.5-kb dsRNA from infected plants represents an
umbravirus, whereas a smaller band (~0.5 kb) is that of a new satellite RNA.
Potato leafroll virus was also consistently associated with the disease. The
three agents, whose experimental host ranges are restricted to members of the
family Solanaceae, always occurred together in field samples and are transmitted
together by the aphid Myzus persicae nicotianae. The umbravirus, which represents
a new species, is most closely related to groundnut rosette virus, and the name
Ethiopian tobacco bushy top virus is proposed.
PMID- 25119678
TI - Molecular detection and characterization of human gyroviruses identified in the
ferret fecal virome.
AB - The recently described novel gyroviruses may infect chickens and/or humans;
however, their pathogenic potential is unknown. In our metagenomic investigation,
we detected many of the novel gyroviruses in the fecal viromes of ferrets with
lymph node and organ enlargement. The complete genomic sequences of selected
gyrovirus strains showed 90.7-99.4 % similarity to homologous reference gyrovirus
strains. This study did not demonstrate an association between gyrovirus shedding
from ferrets and the observed background disease; however, it provides evidence
for genetic diversity among gyroviruses and raises the possibility that pet
ferrets may transmit gyroviruses to heterologous hosts, e.g., humans.
PMID- 25119679
TI - Genetic characterization of porcine kobuvirus and detection of coinfecting
pathogens in diarrheic pigs in Jiangsu Province, China.
AB - In this study, 396 samples from diarrheic pigs on 46 pig farms in Jiangsu
Province, China, were analyzed by RT-PCR. One-hundred eighty-one pigs from 37
farms tested positive for porcine kobuvirus (PKV). Phylogenetic analysis of the
3D gene from 19 isolates showed sequence homology of 88.0 %-100 % and 69.4 %-100
% for nucleotides and amino acids, respectively, while similarity to isolates of
other kobuviruses was 69.6 %-78.8 % and 27.8 %-56.9 %, respectively. One-hundred
eighty-five samples contained two or more pathogens, and 31/68 PKV-positive
samples tested positive for other diarrheic pathogens, confirming the existence
of PKV infection and coinfection.
PMID- 25119681
TI - Near-infrared spectroscopy for monitoring renal transplant perfusion.
PMID- 25119682
TI - Hypervitaminosis A is prevalent in children with CKD and contributes to
hypercalcemia.
AB - BACKGROUND: Vitamin A accumulates in renal failure, but the prevalence of
hypervitaminosis A in children with predialysis chronic kidney disease (CKD) is
not known. Hypervitaminosis A has been associated with hypercalcemia. In this
study we compared dietary vitamin A intake with serum retinoid levels and their
associations with hypercalcemia. METHODS: We studied the relationship between
vitamin A intake, serum retinoid levels, and serum calcium in 105 children with
CKD stages 2-5 on dialysis and posttransplant. Serum retinoid measures included
retinol (ROH), its active retinoic acid (RA) metabolites [all-trans RA (at-RA)
and 13-cis RA] and carrier proteins [retinol-binding protein-4 (RBP4) and
transthyretin (TTR)]. Dietary vitamin A intake was assessed using a food diary.
RESULTS: Twenty-five children were in CKD 2-3, 35 in CKD 4-5, 23 on dialysis and
22 posttransplant; 53 % had vitamin A intake above the Reference Nutrient Intake
(RNI) value. Children receiving supplemental feeds compared with diet alone had
higher vitamin A intake (p = 0.02) and higher serum ROH (p < 0.001). Notably,
increased ROH was seen as early as CKD stage 2. For every 10 ml/min/1.73 m(2)
fall in estimated glomerular filtration rate (eGFR), there was a 13 % increase in
ROH. RBP4 levels were increased in CKD 3-5 and dialysis patients. The lowest
ratios of ROH:RBP4 were seen in dialysis compared with CKD 2-3 (p = 0.03),
suggesting a relative increase in circulating RBP4. Serum ROH, RBP4 and at-RA
were associated with serum calcium. On multivariable analysis RBP4 levels and
alfacalcidol dose were significant predictors of serum calcium (model R (2) 32 %)
in dialysis patients. CONCLUSIONS: Hypervitaminosis A is seen in early CKD, with
highest levels in children on supplemental feeds compared with diet alone. Serum
retinoid levels significantly predict hypercalcemia.
PMID- 25119683
TI - Procalcitonin as a postmortem sepsis marker. A comparison of the validity of
results obtained from blood serum, aqueous humour and cerebrospinal fluid.
AB - In recent years, serum levels of the prohormone procalcitonin have been
investigated in a number of studies in relation to postmortem sepsis diagnostics,
as macroscopic and histomorphological findings are, as a rule, nonspecific.
However, due to advanced haemolysis, it is often not possible to determine serum
procalcitonin (PCT) levels in cases of sepsis-related death. Moreover, the impact
of postmortem interval on PCT levels is largely unclarified. In view of this, the
present pilot study investigated PCT levels in the serum, aqueous humour, and
cerebrospinal fluid in a study population of 25 persons who died of sepsis and a
control population of 25 deaths unrelated to sepsis. Using the Mann-Whitney U
test, statistically significant differences in PCT levels were determined for all
the analysed samples from the study and control populations. Logistic regression
analysis was used to calculate cut-off values for sepsis diagnosis for all the
sample types. Furthermore, the serum elimination rates published by Tsokos et al.
(Int J Legal Med 114:237-243, 2001) were used to calculate the PCT levels at the
time of death for the cases with a known postmortem interval. The results of our
study demonstrate that, taking account of the postmortem elimination process, it
is possible to infer the value at the time of death from the procalcitonin levels
measured in all three sample types and to interpret this with the aid of a
defined cut-off value. The findings need to be verified based on a larger study
population.
PMID- 25119685
TI - Fatal contact shot to the chest caused by the gas jet from a muzzle-loading
pistol discharging only black powder and no bullet: case study and experimental
simulation of the wounding effect.
AB - In modern medico-legal literature, only a small number of publications deal with
fatal injuries from black powder guns. Most of them focus on the morphological
features such as intense soot soiling, blast tattooing and burn effects in close
range shots or describe the wound ballistics of spherical lead bullets. Another
kind of "unusual" and potentially lethal weapons are handguns destined for firing
only blank cartridges such as starter and alarm pistols. The dangerousness of
these guns is restricted to very close and contact range shots and results from
the gas jet produced by the deflagration of the propellant. The present paper
reports on a suicide committed with a muzzle-loading percussion pistol cal. 45.
An unusually large stellate entrance wound was located in the precordial region,
accompanied by an imprint mark from the ramrod and a faint greenish discoloration
(apparently due to the formation of sulfhemoglobin). Autopsy revealed an
oversized powder cavity, multiple fractures of the anterior thoracic wall as well
as ruptures of the heart, the aorta, the left hepatic lobe and the diaphragm. In
total, the zone of mechanical destruction had a diameter of approx. 15 cm. As
there was no exit wound and no bullet lodged in the body, the injury was caused
exclusively by the inrushing combustion gases of the propellant (black powder)
comparable with the gas jet of a blank cartridge gun. In contact shots to
ballistic gelatine using the suicide's pistol loaded with black powder but no
projectile, the formation of a nearly spherical cavity could be demonstrated by
means of a high-speed camera. The extent of the temporary cavity after firing
with 5 g of black powder roughly corresponded to the zone of destruction found in
the suicide's body.
PMID- 25119684
TI - Genetic and forensic implications in epilepsy and cardiac arrhythmias: a case
series.
AB - Epilepsy affects approximately 3% of the world's population, and sudden death is
a significant cause of death in this population. Sudden unexpected death in
epilepsy (SUDEP) accounts for up to 17% of all these cases, which increases the
rate of sudden death by 24-fold as compared to the general population. The
underlying mechanisms are still not elucidated, but recent studies suggest the
possibility that a common genetic channelopathy might contribute to both epilepsy
and cardiac disease to increase the incidence of death via a lethal cardiac
arrhythmia. We performed genetic testing in a large cohort of individuals with
epilepsy and cardiac conduction disorders in order to identify genetic mutations
that could play a role in the mechanism of sudden death. Putative pathogenic
disease-causing mutations in genes encoding cardiac ion channel were detected in
24% of unrelated individuals with epilepsy. Segregation analysis through genetic
screening of the available family members and functional studies are crucial
tasks to understand and to prove the possible pathogenicity of the variant, but
in our cohort, only two families were available. Despite further research should
be performed to clarify the mechanism of coexistence of both clinical conditions,
genetic analysis, applied also in post-mortem setting, could be very useful to
identify genetic factors that predispose epileptic patients to sudden death,
helping to prevent sudden death in patients with epilepsy.
PMID- 25119686
TI - Diagnostic accuracy of pre-bronchodilator FEV1/FEV6 from microspirometry to
detect airflow obstruction in primary care: a randomised cross-sectional study.
AB - BACKGROUND: Forced expiratory volume in 1s/forced expiratory volume in 6 s (
FEV1/FEV6) assessment with a microspirometer may be useful in the diagnostic work
up of subjects who are suspected of having COPD in primary care. AIM: To
determine the diagnostic accuracy of a negative pre-bronchodilator (BD)
microspirometry test relative to a full diagnostic spirometry test in subjects in
whom general practitioners (GPs) suspect airflow obstruction. METHODS: Cross
sectional study in which the order of microspirometry and diagnostic spirometry
tests was randomised. Study subjects were (ex-)smokers aged >=50 years referred
for diagnostic spirometry to a primary care diagnostic centre by their GPs. A pre
BD FEV1/FEV6 value <0.73 as measured with the PiKo-6 microspirometer was compared
with a post-BD FEV1/FVC (forced vital capacity) <0.70 and FEV1/FVC85%). Covariates associated with transitioning between states were examined.
The association between CD3+ T-cell percentage states and time to ADI/death from
cART initiation was determined using Cox proportional hazards models. RESULTS: A
total of 4463 patients were followed for a median of 3 years. Two thousand, five
hundred and eight (56%) patients never transitioned from their baseline CD3+ T
cell percentage state; 85% of these had normal TCH. In multivariable analysis,
individuals with time-updated low CD4+ cell count, time-updated detectable viral
load, older age, and hepatitis C virus (HCV) coinfection were less likely to
maintain TCH. In the multivariable proportional hazards model, both very low and
high CD3+ T-cell percentages were associated with increased risk of ADI/death
[adjusted hazard ratio=1.91 (95% confidence interval, CI: 1.27-2.89) and hazard
ratio=1.49 (95% CI: 1.13-1.96), respectively]. CONCLUSION: Patients with very low
or high CD3+ T-cell percentages are at risk for ADIs/death. To our knowledge,
this is the first study linking altered TCH and morbidity/mortality in cART
treated HIV-positive patients.
PMID- 25119690
TI - Cost-effectiveness of novel algorithms for rapid diagnosis of tuberculosis in HIV
infected individuals in Uganda.
AB - OBJECTIVE: Xpert MTB/RIF ('Xpert') and urinary lateral-flow lipoarabinomannan (LF
LAM) assays offer rapid tuberculosis (TB) diagnosis. This study evaluated the
cost-effectiveness of novel diagnostic algorithms utilizing combinations of Xpert
and LF-LAM for the detection of active TB among people living with HIV. DESIGN:
Cost-effectiveness analysis using data from a comparative study of LF-LAM and
Xpert, with a target population of HIV-infected individuals with signs/symptoms
of TB in Uganda. METHODS: A decision-analysis model compared multiple strategies
for rapid TB diagnosis:sputum smear-microscopy; sputum Xpert; smear-microscopy
combined with LF-LAM; and Xpert combined with LF-LAM. Primary outcomes were the
costs and DALY's averted for each algorithm. Cost-effectiveness was represented
using incremental cost-effectiveness ratios (ICER). RESULTS: Compared with an
algorithm of Xpert testing alone, the combination of Xpert with LF-LAM was
considered highly cost-effective (ICER $57/DALY-averted) at a willingness to pay
threshold of Ugandan GDP per capita. Addition of urine LF-LAM testing to smear
microscopy was a less effective strategy than Xpert replacement of smear
microscopy, but was less costly and also considered highly cost-effective (ICER
$33 per DALY-averted) compared with continued usage of smear-microscopy alone.
Cost-effectiveness of the Xpert plus LF-LAM algorithm was most influenced by
HIV/ART costs and life-expectancy of patients after TB treatment. CONCLUSION: The
addition of urinary LF-LAM to TB diagnostic algorithms for HIV-infected
individuals is highly cost-effective compared with usage of either sputum smear
microscopy or Xpert alone.
PMID- 25119692
TI - Immunologic nonresponders and T-regulatory cells in HIV-1 infection.
PMID- 25119693
TI - Viral and bacterial risks associated with mephedrone abuse in HIV-infected men
who have sex with men.
PMID- 25119687
TI - Frequently asked questions about in vivo chlorophyll fluorescence: practical
issues.
AB - The aim of this educational review is to provide practical information on the
hardware, methodology, and the hands on application of chlorophyll (Chl) a
fluorescence technology. We present the paper in a question and answer format
like frequently asked questions. Although nearly all information on the
application of Chl a fluorescence can be found in the literature, it is not
always easily accessible. This paper is primarily aimed at scientists who have
some experience with the application of Chl a fluorescence but are still in the
process of discovering what it all means and how it can be used. Topics discussed
are (among other things) the kind of information that can be obtained using
different fluorescence techniques, the interpretation of Chl a fluorescence
signals, specific applications of these techniques, and practical advice on
different subjects, such as on the length of dark adaptation before measurement
of the Chl a fluorescence transient. The paper also provides the physiological
background for some of the applied procedures. It also serves as a source of
reference for experienced scientists.
PMID- 25119694
TI - Groundwater quality assessment and its correlation with gastroenteritis using
GIS: a case study of Rawal Town, Rawalpindi, Pakistan.
AB - Majority of the people of Pakistan get drinking water from groundwater source.
Nearly 40 % of the total ailments reported in Pakistan are the result of dirty
drinking water. Every summer, thousands of patients suffer from acute
gastroenteritis in the Rawal Town. Therefore, a study was designed to generate a
water quality index map of the Rawal Town and identify the relationship between
bacteriological water quality and socio-economic indicators with gastroenteritis
in the study area. Water quality and gastroenteritis patient data were collected
by surveying the 262 tubewells and the major hospitals in the Rawal Town. The
collected spatial data was analyzed by using ArcGIS spatial analyst (Moran's I
spatial autocorrelation) and geostatistical analysis tools (inverse distance
weighted, radial basis function, kriging, and cokriging). The water quality index
(WQI) for the study area was computed using pH, turbidity, total dissolved
solids, calcium, hardness, alkalinity, and chloride values of the 262 tubewells.
The results of Moran's I spatial autocorrelation showed that the groundwater
physicochemical parameters were clustered. Among IDW, radial basis function, and
kriging and cokriging interpolation techniques, cokriging showed the lowest root
mean square error. Cokriging was used to make the spatial distribution maps of
water quality parameters. The WQI results showed that more than half of the
tubewells in the Rawal Town were providing "poor" to "unfit" drinking water. The
Pearson's coefficient of correlation for gastroenteritis with fecal coliform was
found significant (P < 0.05) in Water and Sanitation Agency (WASA) zone 2, and
with shortage of toilets, it was significant (P < 0.05) in WASA zones 1 and 3.
However, it was significantly (P < 0.01) inversely related with literacy rate in
WASA zones 1, 2, and 3.
PMID- 25119696
TI - Enhancing the brightness of Si nanocrystal light-emitting devices with electro
excited surface plasmons.
AB - The use of electro-excited surface plasmons (SPs) in Ag nanoparticles (Ag-NPs) is
shown to enhance the brightness of Si nanocrystal light-emitting devices (Si-NC
LEDs). The Ag-NPs are prepared on the Si-NC thin film by ultrasonic irradiation
and postannealing treatments. Electro-excited SPs on Ag-NPs are found, which are
induced by electron impact on Ag-NPs and the front electrode Al layer during the
charge injection process of LED. The electro-excited SPs enhance the
electroluminescence of Si-NC, or LED brightness, via the SP field coupling to the
exciton dipole moment of Si-NC. A maximal 5.2-fold brightness enhancement of Si
NC LED is achieved at the postannealing temperature of 200 degrees C. Remnant
far-field radiations arising from electro-excited SPs are detected, which further
supports the existence of such SPs.
PMID- 25119695
TI - Determination of heavy metal contents in some freshwater fishes.
AB - The concentrations of heavy metals in tench, pike-perch, and common carp fish
caught in four different seasons from Damsa dam lake (Nevsehir) were determined.
Heavy metal contents of fishes changed depending on seasons. The highest Al
(20.894 mg/kg) in tench was established in winter, and the lowest Al (1.605
mg/kg) was determined in summer. Fe content of tench fish changed between 112.906
mg/kg (autumn) and 31.207 mg/kg (spring). In addition, Zn contents of tench were
found between 36.0323 mg/kg (summer) and 430.586 mg/kg (winter). The results
indicate that concentrations of Cu of tench varied from 0.1934 mg/kg (winter) to
15.422 mg/kg (autumn). Results indicate that concentrations varied from 2.923
mg/kg (autumn) to 32.078 mg/kg (summer) with a mean of 11.1893 mg/kg for Al;
0.2483 mg/kg (spring) to 3.3088 mg/kg (autumn) with a mean of 1.6189 mg/kg for
Ni; 0.5325 mg/kg (spring) to 0.845 mg/kg (autumn) with a mean of 0.7234 for Pb;
and 7.0464 mg/kg (winter) to 253.686 mg/kg (summer) with a mean of 133.6348 for
Zn. In common carp, Al, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Zn, Se, Ga, and Te
contents were determined as 3.9623 mg/kg; 0.1293, 0.2336, 0.0526, 0.1543, 4.2406,
0.726, 1.797, 0.6216, 6.8536, 0.1783, 0.7876, and 0.371 mg/kg in autumn,
respectively.
PMID- 25119697
TI - Understanding p53: new insights into tumor suppression.
AB - p53 (aka TP53) is a powerful tumor suppressor, and oncogenic transformation is
induced when the ability of p53 to suppress tumorigenesis is compromised. p53 not
only prevents tumorigenesis, but also tumor progression, that is, local invasion
and distant metastasis. Recently, we showed that cytoplasmic p53 prevents RAS
driven invasion via alteration of actin cytoskeleton remodeling. This follows
modulation of mitochondrial integrity. The transcriptional activity of p53 has
been restored using small molecules; however, their success as cancer therapies
is largely dependent on the status of downstream targets of p53. It is therefore
important to elucidate the role of these downstream targets in p53 regulated
tumor progression. With the recently described mechanism of tumor suppression
highlighting a role of p53's downstream targets in the regulation of actin
cytoskeleton dynamics and lamellipodia formation, we suggest that potential
therapeutic targets may be revealed within this mechanism that can be exploited
in anticancer therapy.
PMID- 25119698
TI - E-health interventions for suicide prevention.
AB - Many people at risk of suicide do not seek help before an attempt, and do not
remain connected to health services following an attempt. E-health interventions
are now being considered as a means to identify at-risk individuals, offer self
help through web interventions or to deliver proactive interventions in response
to individuals' posts on social media. In this article, we examine research
studies which focus on these three aspects of suicide and the internet: the use
of online screening for suicide, the effectiveness of e-health interventions
aimed to manage suicidal thoughts, and newer studies which aim to proactively
intervene when individuals at risk of suicide are identified by their social
media postings. We conclude that online screening may have a role, although there
is a need for additional robust controlled research to establish whether suicide
screening can effectively reduce suicide-related outcomes, and in what settings
online screening might be most effective. The effectiveness of Internet
interventions may be increased if these interventions are designed to
specifically target suicidal thoughts, rather than associated conditions such as
depression. The evidence for the use of intervention practices using social media
is possible, although validity, feasibility and implementation remains highly
uncertain.
PMID- 25119699
TI - Prevalence and antibiogram profiling of Escherichia coli pathotypes isolated from
the Kat River and the Fort Beaufort abstraction water.
AB - Escherichia coli is a widespread bacterium encompassing a variety of strains,
ranging from highly pathogenic strains, causing worldwide outbreaks of severe
diseases to avirulent, well characterized safe laboratory strains. This study
evaluated the prevalence and antibiogram profiles of E. coli pathotypes isolated
from the Kat River and Fort Beaufort abstraction water. A total of 171 out of 278
confirmed E. coli isolates were positive for at least one pathogenic determinant
and these included enteropathogenic E. coli (6%), enterotoxigenic E. coli (47%),
uropathogenic E. coli (2%), neonatal meningitis E. coli (5%), diffusely adherent
E. coli (1%) and enterohaemorrhagic E. coli (1%). Interestingly, enteroinvasive
and enteroaggregative E. coli were not detected. The phenotypic antibiogram
profiles of the isolates revealed that all were resistant to penicillin G, while
98% and 38% of the pathotypes were resistant to ampicillin and trimethoprim
sulphamethoxazole, respectively. About 8% of the isolates were resistant to
streptomycin. More than half of the isolates exhibited multiple antibiotic
resistance with 44% being resistant to three antibiotics and 8% resistant to four
antibiotics. We conclude that the Kat River is a reservoir of potentially
virulent antibiotic resistant E. coli strains that can cause serious health risks
to humans who drink raw water from this river, or in the case that consumption of
treated drinking water coincides with failed drinking water processes.
PMID- 25119701
TI - [Aging and climate change: impact on health-related quality of life].
PMID- 25119700
TI - Type and course of symptoms demonstrated in the terminal and dying phases by
people with dementia in nursing homes.
AB - BACKGROUND: In all, 39 % of people living in Swiss nursing homes suffer from
dementia. Detailed data about type and course of symptoms displayed by these
patients in their terminal phase are lacking. METHODS: This descriptive,
retrospective study analysed 65 nursing documents from deceased people with
dementia in four nursing homes in the canton of Zurich, Switzerland. RESULTS:
Difficulties with mobility (81 %), pain (71 %) and sleep disturbance (63 %) were
the most frequent of the 10 identified symptoms. Towards the end of life,
difficulties with mobility, sleep disturbance, agitation and other
neuropsychiatric symptoms, such as episodes of depression, decreased (decrescent
pattern), while pain, feeding problems, breathing abnormalities, apathy and
anxiety increased (crescent pattern). Courses of pain were documented in 17 % of
the nursing records. In addition, 76 % of the residents had been visited on a
daily basis by next of kin in their last 7 days, compared with only one third of
residents previously. Furthermore, daily communication between healthcare
professionals and next of kin tripled during this period. CONCLUSION: The
documented prevalence of a high and increasing level of pain towards the end of
life, combined with the lack of documented courses of pain, shows potential for
improvement in pain relief and pain identification for patients with dementia in
their terminal phase. The increasing number of visits by next of kin and the
increasingly intensive contact between healthcare professionals and next of kin
in the last 7 days are a strong indicator that the end of life can be predicted
relatively well by the involved participants and appropriate reactions follow.
PMID- 25119702
TI - Heat waves and mortality in Frankfurt am Main, Germany, 2003-2013: what effect do
heat-health action plans and the heat warning system have?
AB - Following the heat wave of August 2003 that caused over 70,000 fatalities in
Western Europe, heat-health action plans (HHAP) and heat warning systems were
implemented in many European countries, including Germany. The effect of these
preventive measures (informing the population as well as nursing and medical
personnel) on excess mortality during heat waves in Frankfurt am Main, Germany,
is studied, taking into account newly published data on a modifying effect of air
pollution on heat mortality. MATERIAL AND METHOD: Mortality data comprising all
deaths registered in the city of Frankfurt was obtained from the statistical
state office; air temperature and air pollution data in Frankfurt Ost were
obtained from the Hessian state office for environment and geology. SPSS Version
15 was used for statistical analysis (bivariate and partial correlations,
nonparametric tests/Kruskal-Wallis, and Mann-Whitney test). RESULTS: Temperature
data as well as air pollution and daily mortality exhibited extreme values in
summer 2003 compared to the summer periods 2004-2013. Never again were such
levels of temperature and air pollution reached. In 2003, excess mortality was
78%, and as high as 113% among the population aged >80 years. During the heat
wave of 2010, the total excess mortality was 23% (significant) and 38% in the
population aged >80 years, while during heat waves in 2006 and 2013 no
significant increase in total mortality was seen (total excess mortality 12% and
4%; not significant). CONCLUSION: Lower excess mortality could be seen in
Frankfurt am Main during heat waves following the implementation of HHAP and the
heat warning system. This might be an effect of the measures implemented by the
HHAP to reduce heat mortality. However, it cannot be ruled out that this might
also be an effect of shorter heat wave periods and lower air pollution in the
subsequent years. Therefore, further efforts are needed to improve the resilience
of the population, especially the elderly population, to better cope with heat
waves.
PMID- 25119703
TI - The challenges posed by climate change to successful ageing.
AB - Ever since the 2003 heat wave that caused 70,000 heat deaths, the dramatic
consequences of climate change and rising temperatures in Europe have become an
intensively researched topic. During heat waves, the older urban adult population
is at highest risk. The STOPHOT project is the first investigation in Austria to
establish a comprehensive knowledge base on heat perception, awareness of heat
risks and adaptive/coping behaviours among older adults. The main research
questions include: (1) Does climate change endanger the chances of successful
ageing in urban areas? (2) How do age, social inequalities and the living
environment intersect with environmental stressors in affecting successful
ageing? (3) Which heat adaption strategies do older adults deploy and to what
extent can they mediate heat stress in an effort to increase chances of
successful ageing under the conditions of climate change? The results indicate
that climate change and rising temperatures are in fact one important determinant
of whether and how an older person can maintain well-being in later life. Older
adults (> 65 years) with a low socio-economic status and poor health conditions,
who tend to be socially isolated, are most at risk. However, no 'heat island
effect' of the residential environment could be found. How much a person suffers
from heat stress is highly dependent on the adaption strategies deployed.
Adaption strategies of older urban residents mostly centred on body-related
measures, such as drinking more or wearing lighter clothes, and indoor-centred
measures, particularly avoiding the outdoors.
PMID- 25119704
TI - Comprehension of climate change and environmental attitudes across the lifespan.
AB - Given the coincidence of the demographic change and climate change in the
upcoming decades the aging voter gains increasing importance in climate change
mitigation and adaptation processes. It is generally assumed that information
status and comprehension of complex processes underlying climate change are
prerequisites for adopting pro-environmental attitudes and taking pro
environmental actions. In a cross-sectional study, we investigated in how far (1)
environmental knowledge and comprehension of feedback processes underlying
climate change and (2) pro-environmental attitudes change as a function of age.
Our sample consisted of 92 participants aged 25-75 years (mean age 49.4 years, SD
17.0). Age was negatively related to comprehension of system structures inherent
to climate change, but positively associated with level of fear of consequences
and anxiousness towards climate change. No significant relations were found
between environmental knowledge and pro-environmental attitude. These results
indicate that, albeit understanding of relevant structures of the climate system
is less present in older age, age is not a limiting factor for being engaged in
the complex dilemma of climate change. Results bear implications for the
communication of climate change and pro-environmental actions in aging societies.
PMID- 25119705
TI - [Health protection during heat waves: European recommendations and experience in
Hesse].
AB - BACKGROUND: In the course of climate change periods of extreme heat will probably
happen more frequently. The aim of heat health action plans is to prevent the
health consequences of heat. OBJECTIVES: The purpose of the present work is to
develop a proposal for a heat health action plan for Hesse, Germany. MATERIALS
AND METHODS: In 34 interviews with experts the existing heat health warning
system was evaluated. Heat health action plans of 8 European countries were
analysed. On this basis a concept for a heat health action plan for Hesse was
developed. RESULTS: In Hesse only nursing homes take preventative measures
reliably, other health care sectors act along varying individual criteria. Heat
health action plans include a heat health warning system and measures. They
arrange competences and risk communication. Local authorities are responsible for
implementation. Some plans include a surveillance system of mortality or
morbidity. In a heat health action plan for Hesse measures should be specified
and adapted to specific needs on the local level. Physicians in outpatient
clinics are in a key position having contact with the vulnerable group of the
elderly. CONCLUSION: A heat health action plan offers opportunities for effective
prevention if responsibilities are defined and evaluated, and monitoring of
mortality and morbidity is integrated. In the structures of the German health
care system efforts to prevent heat-related illness cannot succeed without
reliable participation of the outpatient medical system.
PMID- 25119706
TI - Efficacy of new pediatric extra-corporeal life support system (Endumo 2000) for
postoperative management after Norwood operation.
AB - This study aimed to assess the efficacy of a new pediatric extra-corporeal life
support (ECLS) system (Endumo 2000, Heiwa Bussan, Tokyo, Japan) for postoperative
management after the Norwood operation. Thirty-three consecutive patients with
hypoplastic left heart syndrome or its variant undergoing the Norwood operation
between August 2007 and December 2013 were divided into two groups according to
available ECLS devices. Before November 2009, pediatric Emersave (TERUMO,
Saitama, Japan) was employed as the ECLS device, and 14 patients were operated on
during this period (Emersave era: 7 boys; 2.9 kg). After December 2009, Endumo
2000 was employed and 19 patients were operated on (Endumo era: 8 boys, 3.1 kg).
The demographic characteristics of both groups showed no significant differences.
ECLS was initiated in 7 of 14 patients (50%) during the Emersave era and 7 of 19
patients (37%) during the Endumo era (p = 0.45). Chest reentry for hemostasis
during ECLS support was more frequently needed in patients supported by Emersave
(5/7) than Endumo (1/7) (p = 0.03). The first ECLS circuit durability of Endumo
was significantly longer than that of Emersave (p = 0.01). The survival at
discharge rate in patients required ECLS was 0% (0/7) when supported by Emersave,
but 57% (4/7) by Endumo (p = 0.02). As a result, the survival at discharge rate
was 43% (6/14) in the Emersave era and 79% (14/19) in the Endumo era (p = 0.03).
Longer durability and superior antithrombogenicity of the Endumo 2000 contributed
to the improvement of surgical outcomes after the Norwood operation.
PMID- 25119707
TI - Trace elements concentration in nails and association with airway inflammation in
adolescents.
AB - Asthma is a multifactorial disease and its severity varies with the inflammatory
status of the patient. It has been hypothesized that deficiency of trace elements
has an important role in the etiology of asthma. The aim of the study was to
evaluate the concentration of trace elements in nails of adolescents with
different degrees of airway inflammation. We assessed the prevalence of active
and severe asthma in adolescents (n = 106) through the ISAAC questionnaire.
Subjects were allocated into two different groups according to the value of
fraction exhaled nitric oxide (FeNO) measured. Also, nail specimens were
collected in order to determine the concentration of accumulated trace elements
(Cu, Zn, Mn, Se) by ICP-MS. It was performed Student's t test to evaluate
statistical differences between inflammatory groups considering normally
distributed data. On the other hand, when data presented non-normal distribution,
Mann-Whitney U test was utilized. Spearman coefficients were calculated to
investigate correlations between FeNO and mineral concentrations. Exhaled NO was
increased in male subjects. We found association between active asthma and
elevated exhaled NO. There was no significant difference in Cu (4.40 vs. 4.52),
Zn (84.66 vs. 79.48), Mn (0.59 vs. 0.76), and Se (0.18 vs. 0.19) concentrations
(MUg/g) among distinct FeNO groups as well as was not observed correlation
between exhaled NO levels and any element. Deficiency of trace elements in nails
were not associated with increased FeNO.
PMID- 25119708
TI - Anatomical region differences and age-related changes in copper, zinc, and
manganese levels in the human brain.
AB - Using inductively coupled plasma-mass spectrometry after samples microwave
assisted acid digestion, zinc (Zn), copper (Cu), and manganese (Mn) levels were
measured in 14 different areas of the human brain of adult individuals (n = 42;
71 +/- 12, range 50-101 years old) without a known history of neurodegenerative,
neurological, or psychiatric disorder. The main goals of the work were to
establish the "normal" (reference) values for those elements in the human brain
and to evaluate the age-related changes, a prior and indispensable step in order
to enlighten the role of trace element (TE) in human brain physiology and their
involvement in aging and neurodegenerative processes. Considering the mean values
for the 14 regions, Zn (mean +/- sd; range 53 +/- 5; 43-61 MUg/g) was found at
higher levels, followed by Cu (22 +/- 5; 10-37 MUg/g) and Mn (1.3 +/- 0.3; 0.5
2.7 MUg/g). The TE distribution across the brain tissue showed to be quite
heterogeneous: the highest levels of Zn were found in the hippocampus (70 +/- 10;
49-95 MUg/g) and superior temporal gyrus (68 +/- 10; 44-88 MUg/g) and the lowest
in the pons (33 +/- 8; 19-51 MUg/g); the highest levels of Cu and Mn were found
in the putamen (36 +/- 13; 21-76 MUg/g and 2.5 +/- 0.8; 0.7-4.5 MUg/g,
respectively) and the lowest in the medulla (11 +/- 6; 2-30 MUg/g and 0.8 +/-
0.3; 0.2-1.8 MUg/g, respectively). A tendency for an age-related increase in Zn
and Mn levels was observed in most brain regions while Cu levels showed to be
negatively correlated with age.
PMID- 25119709
TI - Analysis of the DNA interaction of copper compounds belonging to the
Casiopeinas(r) antitumoral series.
AB - Casiopeinas(r) are mixed-chelate copper complexes with antitumor tested
potential. Their activity, both in vitro and in vivo, as antiproliferative,
cytotoxic, and genotoxic drugs has been assessed. Biological results of these
copper compounds have deserved some of them entering clinical trials. Significant
efforts have been devoted to the in-depth identification of their mechanism of
action. Using gel electrophoresis analysis, we have previously shown that the
interaction of the Casiopeinas(r) Cas II-gly, [Cu(4,7-dimethyl-1,10
phenanthroline)(glycinate)]NO3 with DNA, triggers the cleavage of the biomolecule
by a free radical mechanism. In this work, we further study the behavior of
different complexes of the same Casiopeinas(r) series also including glycinate as
co-ligand {Cas VI-gly (5,6 dimethyl-1,10-phenanthroline glycinato copper(II)
nitrate), Cas VII-gly (1,10-phenanthroline glycinato copper(II) nitrate), and Cas
IX-gly (2,2'-bipyridine glycinato copper(II) nitrate)} and of a Casiopeinas(r)
with a different co-ligand (Cas III-Cs; 4,7-dimethyl-1,10-phenanthroline
salicylaldehydato-copper(II) nitrate). While all of them produce DNA degradation,
the performance in the presence of a radical scavenger suggests the existence of
differences in their mechanism of interaction with DNA.
PMID- 25119710
TI - It is my great pleasure to welcome you to the third issue of 2014. Introduction.
PMID- 25119711
TI - Effects of Ti surface treatments with silane and arginylglycylaspartic acid
peptide on bone cell progenitors.
AB - Achieving optimal aesthetic appearance is a major objective in dental implant
design, and the interaction between the materials and the bone cell progenitors
is an important factor in the attainment of this objective. In this study, a
novel concept was evaluated by varying the surface modifications on titanium
(Ti). Different levels of roughness can be attained by machine grinding (M), sand
blasting, and acid etching (SLA) of the samples. The behavior of bone cell
progenitors (D1) on the surfaces of Ti disks with different surface modifications
was investigated. The surfaces of M or SLA disks were silanized (MS or SLAS
group) through treatment with silane/Gly-Arg-Gly-Asp-Ser (GRGDS) peptide (MSP or
SLASP group) and anchored particles of tetracalcium phosphate (TTCP) on the
specimen surfaces (SLA-TTCP group). Physicochemical analysis was performed by
metallographic microscopy, scanning electron microscopy, and contact angle
analysis. The proliferation and the quantitative alkaline phosphatase (ALP)
production of D1 cells on the surface of different sample groups were determined.
The SLASP group had a significantly larger D1 cell proliferation than the other
groups after 4 and 7 d of incubation (p < 0.05). ALP expression was a very early
marker of differentiation, and was the first indication of the increasing number
of cells at 7 d of culture. Among the groups in the M substrate series (i.e., M,
MS, and MSP) and in the SLA series (i.e., SLA, SLAS, and SLASP), the MSP and
SLASP specimens exhibited superior differentiation abilities on respective
cultures until day 7 and day 10. A high number of hydrophilic surfaces dominated
cell proliferation in the early stage of cell attachment. However, factors
affecting the pore structure and the surface morphology can improve cell
proliferation and differentiation. According to analyses of proliferation and ALP
expression of bone cell progenitors D1, the original SLA implant surface can be
improved with surface treatment methods, such as silanization and treatment with
graft GRGDS pentapeptide. These methods can be potential candidates for the
promotion of bone growth.
PMID- 25119712
TI - Correlation between SNP genotypes and periodontitis in Japanese type II diabetic
patients: a preliminary study.
AB - The present study aims to investigate the correlation between SNP genotype
patterns and periodontitis severity in Japanese type II diabetic patients. A
cross-sectional study in 43 Japanese diabetic patients with periodontitis was
performed. Blood samples were drawn for single nucleotide polymorphism (SNP)
analyses and periodontal index (probing pocket depth and clinical attachment
level) was subsequently recorded. Twelve functional genes with SNPs that had been
shown to be associated with diabetes and/or inflammation were genotyped using a
nuclease-mediated SNP-specific ligation method. Subjects with two or more sites
with clinical attachment level >=6 mm and who additionally had one or more sites
with pocket depth >=5 mm were classified as having severe periodontitis.
Proportions of risk genotypes/non-risk genotypes between severe and non-severe
periodontitis were subsequently compared. A high frequency (21/43 participants,
49%) of adiponectin gene polymorphism (ADIPOQ 45T > G) homozygous risk genotype
(TT genotype) was observed in the participants. The frequency of TGF-beta1 SNP
(29C > T) risk genotype (TT genotype) in severe periodontitis (34%, n = 11) was
significantly higher than in non-severe periodontitis (0%, n = 0) (p = 0.04). Our
study suggests that TGF-beta1 SNPs (29C > T) may be used as one of the risk
indicators for severe periodontitis in Japanese diabetic patients.
PMID- 25119714
TI - A time series evaluation of the FAST National Stroke Awareness Campaign in
England.
AB - OBJECTIVE: In February 2009, the Department of Health in England launched the
Face, Arm, Speech, and Time (FAST) mass media campaign, to raise public awareness
of stroke symptoms and the need for an emergency response. We aimed to evaluate
the impact of three consecutive phases of FAST using population-level measures of
behaviour in England. METHODS: Interrupted time series (May 2007 to February
2011) assessed the impact of the campaign on: access to a national stroke
charity's information resources (Stroke Association [SA]); emergency hospital
admissions with a primary diagnosis of stroke (Hospital Episode Statistics for
England); and thrombolysis activity from centres in England contributing data to
the Safe Implementation of Thrombolysis in Stroke UK database. RESULTS: Before
the campaign, emergency admissions (and patients admitted via accident and
emergency [A&E]) and thrombolysis activity was increasing significantly over
time, whereas emergency admissions via general practitioners (GPs) were
decreasing significantly. SA webpage views, calls to their helpline and
information materials dispatched increased significantly after phase one. Website
hits/views, and information materials dispatched decreased after phase one; these
outcomes increased significantly during phases two and three. After phase one
there were significant increases in overall emergency admissions (505, 95% CI =
75 to 935) and patients admitted via A&E (451, 95% CI = 26 to 875). Significantly
fewer monthly emergency admissions via GPs were reported after phase three (-19,
95% CI = -29 to -9). Thrombolysis activity per month significantly increased
after phases one (3, 95% CI = 1 to 6), and three (3, 95% CI = 1 to 4).
CONCLUSIONS: Phase one had a statistically significant impact on information
seeking behaviour and emergency admissions, with additional impact that may be
attributable to subsequent phases on information seeking behaviour, emergency
admissions via GPs, and thrombolysis activity. Future campaigns should be
accompanied by evaluation of impact on clinical outcomes such as reduced stroke
related morbidity and mortality.
PMID- 25119713
TI - Analysis of the relationship between periodontal disease and atherosclerosis
within a local clinical system: a cross-sectional observational pilot study.
AB - It has been revealed that atherosclerosis and periodontal disease may have a
common mechanism of "chronic inflammation". Several reports have indicated that
periodontal infection is related to atherosclerosis, but none have yet reported
such an investigation through the cooperation of local clinics. This study was
performed in local Japanese clinics to examine the relationship between
periodontal disease and atherosclerosis under collaborative medical and dental
care. A pilot multicenter cross-sectional study was conducted on 37 medical
patients with lifestyle-related diseases under consultation in participating
medical clinics, and 79 periodontal patients not undergoing medical treatment but
who were seen by participating dental clinics. Systemic examination and
periodontal examination were performed at baseline, and the relationships between
periodontal and atherosclerosis-related clinical markers were analyzed. There was
a positive correlation between LDL-C level and plasma IgG antibody titer to
Porphyromonas gingivalis. According to the analysis under adjusted age, at a cut
off value of 5.04 for plasma IgG titer to Porphyromonas gingivalis, the IgG titer
was significantly correlated with the level of low-density lipoprotein
cholesterol (LDL-C). This study suggested that infection with periodontal
bacteria (Porphyromonas gingivalis) is associated with the progression of
atherosclerosis. Plasma IgG titer to Porphyromonas gingivalis may be useful as
the clinical risk marker for atherosclerosis related to periodontal disease.
Moreover, the application of the blood examination as a medical check may lead to
the development of collaborative medical and dental care within the local medical
clinical system for the purpose of preventing the lifestyle-related disease.
PMID- 25119715
TI - Do simultaneously viewed objects influence scene recognition individually or as
groups? Two perceptual studies.
AB - The ability to quickly categorize visual scenes is critical to daily life,
allowing us to identify our whereabouts and to navigate from one place to
another. Rapid scene categorization relies heavily on the kinds of objects scenes
contain; for instance, studies have shown that recognition is less accurate for
scenes to which incongruent objects have been added, an effect usually
interpreted as evidence of objects' general capacity to activate semantic
networks for scene categories they are statistically associated with. Essentially
all real-world scenes contain multiple objects, however, and it is unclear
whether scene recognition draws on the scene associations of individual objects
or of object groups. To test the hypothesis that scene recognition is steered, at
least in part, by associations between object groups and scene categories, we
asked observers to categorize briefly-viewed scenes appearing with object pairs
that were semantically consistent or inconsistent with the scenes. In line with
previous results, scenes were less accurately recognized when viewed with
inconsistent versus consistent pairs. To understand whether this reflected
individual or group-level object associations, we compared the impact of pairs
composed of mutually related versus unrelated objects; i.e., pairs, which, as
groups, had clear associations to particular scene categories versus those that
did not. Although related and unrelated object pairs equally reduced scene
recognition accuracy, unrelated pairs were consistently less capable of drawing
erroneous scene judgments towards scene categories associated with their
individual objects. This suggests that scene judgments were influenced by the
scene associations of object groups, beyond the influence of individual objects.
More generally, the fact that unrelated objects were as capable of degrading
categorization accuracy as related objects, while less capable of generating
specific alternative judgments, indicates that the process by which objects
interfere with scene recognition is separate from the one through which they
inform it.
PMID- 25119716
TI - Movements of blue sharks (Prionace glauca) across their life history.
AB - Spatial structuring and segregation by sex and size is considered to be an
intrinsic attribute of shark populations. These spatial patterns remain poorly
understood, particularly for oceanic species such as blue shark (Prionace
glauca), despite its importance for the management and conservation of this
highly migratory species. This study presents the results of a long-term
electronic tagging experiment to investigate the migratory patterns of blue
shark, to elucidate how these patterns change across its life history and to
assess the existence of a nursery area in the central North Atlantic. Blue sharks
belonging to different life stages (n = 34) were tracked for periods up to 952
days during which they moved extensively (up to an estimated 28.139 km),
occupying large parts of the oceanic basin. Notwithstanding a large individual
variability, there were pronounced differences in movements and space use across
the species' life history. The study provides strong evidence for the existence
of a discrete central North Atlantic nursery, where juveniles can reside for up
to at least 2 years. In contrast with previously described nurseries of coastal
and semi-pelagic sharks, this oceanic nursery is comparatively vast and open
suggesting that shelter from predators is not its main function. Subsequently,
male and female blue sharks spatially segregate. Females engage in seasonal
latitudinal migrations until approaching maturity, when they undergo an ontogenic
habitat shift towards tropical latitudes. In contrast, juvenile males generally
expanded their range southward and apparently displayed a higher degree of
behavioural polymorphism. These results provide important insights into the
spatial ecology of pelagic sharks, with implications for the sustainable
management of this heavily exploited shark, especially in the central North
Atlantic where the presence of a nursery and the seasonal overlap and alternation
of different life stages coincides with a high fishing mortality.
PMID- 25119718
TI - At-sea associations in foraging little penguins.
AB - Prey distribution, patch size, and the presence of conspecifics are important
factors influencing a predator's feeding tactics, including the decision to feed
individually or socially. Little is known about group behaviour in seabirds as
they spend most of their lives in the marine environment where it is difficult to
observe their foraging activities. In this study, we report on at-sea foraging
associations of little penguins (Eudyptula minor) during the breeding season.
Individuals could be categorised as (1) not associating; (2) associating when
departing from and/or returning to the colony; or (3) at sea when travelling,
diving or performing synchronised dives. Out of 84 separate foraging tracks, 58
(69.0%) involved associations with conspecifics. Furthermore, in a total of 39
(46.4%), individuals were found to dive during association and in 32 (38.1%),
individuals were found to exhibit synchronous diving. These behaviours suggest
little penguins forage in groups, could synchronise their underwater movements
and potentially cooperate to concentrate their small schooling prey.
PMID- 25119720
TI - Recognition of elementary arm movements using orientation of a tri-axial
accelerometer located near the wrist.
AB - In this paper we present a method for recognising three fundamental movements of
the human arm (reach and retrieve, lift cup to mouth, rotation of the arm) by
determining the orientation of a tri-axial accelerometer located near the wrist.
Our objective is to detect the occurrence of such movements performed with the
impaired arm of a stroke patient during normal daily activities as a means to
assess their rehabilitation. The method relies on accurately mapping transitions
of predefined, standard orientations of the accelerometer to corresponding
elementary arm movements. To evaluate the technique, kinematic data was collected
from four healthy subjects and four stroke patients as they performed a number of
activities involved in a representative activity of daily living, 'making-a-cup
of-tea'. Our experimental results show that the proposed method can independently
recognise all three of the elementary upper limb movements investigated with
accuracies in the range 91-99% for healthy subjects and 70-85% for stroke
patients.
PMID- 25119719
TI - Modified treatment approach using cardiovascular disease risk calculator for
primary prevention.
AB - BACKGROUND: The recent guidelines for preventing atherosclerotic cardiovascular
events are an important advancement. For primary prevention, statins are
recommended if the ten-year risk is >= 5% (consideration for therapy) or >= 7.5%
(definitive treatment unless contraindication after discussion). We rationalized
that a significant cohort with ten-year risk below the treatment thresholds would
predictably surpass them within the recommended 4-6 year window for reassessing
the ten-year risk. As atherosclerosis is a progressive disease, these individuals
may therefore benefit with more aggressive therapies even at baseline. METHODS
AND FINDINGS: We used publicly available NHANES dataset for ten-year risk
calculation. There were 1805 participants. To evaluate the ten-year risk change
at five years, we considered two scenarios: no change in the baseline parameters
except increased age by five (No Change) and alternatively 10% improvement in
systolic BP, total and HDL-c, no smoking with five-year increase in age (Reduced
Risk Profile). Amongst non-diabetics with <5% risk at baseline, 35% reached or
exceeded 5% risk in five years (5% reached or exceed the 7.5% risk) with No
Change and 9% reached or exceeded 5% risk in five years (none reached 7.5% risk)
with Reduced Risk Profile; furthermore, 94% of the non-diabetic cohort with
baseline risk between 3.5%-5% would exceed the 5% and/or 7.5% boundary limit with
No Change. Amongst non-diabetics with 5-7.5% baseline risks, 87% reached or
exceeded 7.5% with No Change while 30% reached or exceeded 7.5% risk with Reduced
Risk Profile. CONCLUSIONS: A significant population cohort at levels below the
treatment thresholds will predictably exceed these limits with time with or
without improvement in modifiable risk factors and may benefit with more
aggressive therapy at baseline. We provide an improved risk calculator that
allows for integrating expected risk modification into discussion with an
individual. This needs to be prospectively tested in clinical trials.
PMID- 25119717
TI - Divergent effects of liraglutide, exendin-4, and sitagliptin on beta-cell mass
and indicators of pancreatitis in a mouse model of hyperglycaemia.
AB - AIMS: Glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase
4 (DPP4) inhibitors improve glucose tolerance by still incompletely understood
mechanisms. Each class of antihyperglycemic drugs has also been proposed to
increase pancreatitis risk. Here, we compare systematically the effects of two
widely-used GLP-1 analogues, liraglutide and exendin-4, and the DPP4 inhibitor,
sitagliptin, in the mouse. METHODS: C57BL6 mice were maintained for 131 days on a
normal diet (ND) or a diet comprising 60% fat (HFD) before measurements of
fasting blood glucose and insulin, and intraperitoneal glucose tolerance. Beta-
and alpha- cell volume, and Reg3b immunoreactivity, were measured by
immunohistochemical analysis of pancreatic slices. RESULTS: Whereas liraglutide
(200 ug/kg) and exendin-4 (10 ug/kg) treatment reduced body weight and/or
improved glucose tolerance, sitagliptin (10 mg/kg) was without effect on either
parameter. Liraglutide caused a sharp reduction in beta-cell mass in both ND and
HFD mice, whereas exendin-4 exerted no effect. By contrast, sitagliptin unmasked
an action of high fat diet to increase beta-cell mass. Reg3B positive area was
augmented by all three agents in normal chow-fed mice, whilst sitagliptin and
exendin-4, but not liraglutide, affected this parameter in HFD animals.
Correspondingly sitagliptin, but not the GLP-1 analogues, increased circulating
amylase levels in ND and HFD mice. CONCLUSIONS: Liraglutide improves glucose
tolerance in the mouse whilst exerting relatively modest effects on pancreatitis
risk. Conversely, exendin-4 and sitagliptin, at doses which exert, respectively,
minor or no effects on metabolic parameters, lead to signs of pancreatitis.
PMID- 25119721
TI - Dolichoectasia and the risk of stroke and vascular disease: a critical appraisal.
AB - Dolichoectasia (DE) in cerebral arteries is a poorly understood arteriopathy that
has been associated with increased risk of vascular morbidity and mortality.
Dolichoectasia tends to affects older individuals with vascular risk factors, but
it can also be secondary to specific conditions related with extracellular matrix
health. The range of methods used to study DE and the biases inherent to hospital
based samples weaken the generalizability of DE study results to the general
population. Within the context of these limitations, there is growing evidence
that DE is a serious condition that can increase the risk of vascular death.
Recurrent strokes and compressive symptoms are among the major causes of
morbidity, but cardiac ischemic disease and aortic aneurysms are not uncommon in
populations with DE. The devastating outcomes of patients with DE are a call to
action aimed at improving the quality of research on the topic and discovering
therapies that can palliate the burden of DE in the population.
PMID- 25119723
TI - Targeted delivery of doxorubicin to A549 lung cancer cells by CXCR4 antagonist
conjugated PLGA nanoparticles.
AB - Doxorubicin is used to treat a variety of cancers, but dose limiting toxicity or
intrinsic and acquired resistance limits its application in many types of cancer.
CXCR4 is a chemokine receptor which implicates in metastasis of cancers including
lung cancer. LFC131, a peptide inhibitor of CXCR4-ligand binding, is a linear
type of low molecular weight CXCR4 antagonist. In this study, we investigated the
possibility of using LFC131 conjugated nanoparticles for targeted delivering
doxorubicin to CXCR4 expressing lung cancer cells. The LFC131 peptide was
conjugated to sodium carboxylmethyl cellulose coated poly(dl-lactic-co-glycolic
acid) (PLGA) nanoparticles. Binding and cellular uptake of doxorubicin-loaded
LFC131 conjugated nanoparticles (LFC131-DOX NP) in adenocarcinomic human alveolar
basal epithelial cells called A549 cells were higher and faster than that of
untargeted nanoparticles. The specificity of CXCR4-mediated internalization of
LFC131-DOX NPs was confirmed by using free LFC131 peptide or anti-CXCR4
monoclonal antibody. Cell studies suggested that sustained release of doxorubicin
afforded by PLGA nanoparticles may enable LFC131-DOX NP as a targeted and
controlled release drug delivery system.
PMID- 25119722
TI - The evaluation and treatment of endocrine forms of hypertension.
AB - Endocrine hypertension is an important secondary form of hypertension, identified
in between 5% and 10% of general hypertensive population. Primary aldosteronism
is the most common cause of endocrine hypertension, accounting for 1%-10% in
uncomplicated hypertension and 7%-20% in resistant hypertension. Other less
common causes of endocrine hypertension include Cushing syndrome,
pheochromocytoma, thyroid disorders, and hyperparathyroidism. Diagnosis requires
a high index of suspicion and the use of appropriate screening tests based on
clinical presentation. Failure to make proper diagnosis may lead to catastrophic
complications or irreversible hypertensive target organ damage. Accordingly,
patients who are suspected to have endocrine hypertension should be referred to
endocrinologists or hypertension specialists who are familiar with management of
the specific endocrine disorders.
PMID- 25119725
TI - Towards a sustainable world through human factors and ergonomics: it is all about
values.
AB - In this paper, we analyse two approaches that attempt to address how a human
factors and ergonomics (HFE) perspective can contribute to the sustainability of
the human race. We outline the principles, purposes and fields of application of
ergoecology and green ergonomics, and thereafter deal with their context of
emergence, and the overlaps in purpose, and principles. Shared values are deduced
and related to socio-technical principles for systems' design. Social
responsibility and environmental/ecospheric responsibility are the leading
threads of ergoecology and green ergonomics, giving rise to the values of:
respect for human rights, respect for the Earth, respect for ethical decision
making, appreciation of complexity, respect for transparency and openness, and
respect for diversity. We discuss the consequences of considering these values in
HFE theory and practice.
PMID- 25119724
TI - Nonparametric method for detecting imprinting effect using all members of general
pedigrees with missing data.
AB - Imprinting effects can lead to parent-of-origin patterns in complex human
diseases. For a diallelic marker locus, Pedigree Parental-Asymmetry Test (PPAT)
and its extension MCPPAT using pedigrees allowing for missing genotypes are
simple and powerful for detecting imprinting effects. However, these approaches
only take affected offspring into consideration, thus not making full use of the
data available. In this paper, we propose Monte Carlo Pedigree Parental-Asymmetry
Test using both affected and unaffected (MCPPATu) offsprings, which allows for
missing genotypes through Monte Carlo sampling. Simulation studies demonstrate
that MCPPATu controls the empirical type I error rate well under the null
hypotheses of no parent-of-origin effects. It is also demonstrated that the use
of additional information from unaffected offspring and partially observed
genotypes in the analysis can greatly improve the statistical power. Indeed, for
common diseases, MCPPATu is much more powerful than MCPPAT when all genotypes are
observed and the power improvement is even greater when there is missing data.
For rarer diseases, there are still substantial power gains with the inclusion of
unaffected offspring, although the gains are less impressive compared with those
for more common diseases.
PMID- 25119728
TI - Effect of obesity on aromatase inhibitor efficacy in postmenopausal, hormone
receptor-positive breast cancer: a systematic review.
AB - Aromatase inhibitors (AIs) decrease the production of oestrogen, decreasing
stimulation of hormone receptor-positive breast cancer. Theoretically, AIs may be
less effective in obese women, due to the greater quantity of aromatase in
peripheral fatty tissue. We performed a systematic review to assess the effect of
obesity on AI efficacy in breast cancer treatment. The review followed PRISMA
guidelines. Studies included were interventional or observational studies with
comparison groups, of postmenopausal women with hormone receptor-positive breast
cancer on treatment with an AI, alone or in combination with other drugs, in
which body mass index or another measure of obesity was recorded. Studies in all
languages were included; if published as an abstract only, authors were contacted
for further information. Outcome measures included overall survival, disease-free
survival or time to progressive disease, survival from the start of therapy,
mortality measures, local or distant recurrence of primary cancer and time to
recurrence. Of 2,344 citations identified from five databases, eight studies met
the criteria for inclusion; three randomised controlled trials and five
retrospective cohort studies. Due to variability in study factors, it was not
possible to perform a quantitative meta-analysis. However, the systematic review
showed a trend towards a negative effect of obesity on AI efficacy. There is
evidence of a negative effect of obesity on AI efficacy in postmenopausal hormone
receptor-positive breast cancer, but the size of the effect cannot be assessed.
More information is needed before clinical recommendations are made.
PMID- 25119727
TI - Women's empowerment and contraceptive use: the role of independent versus
couples' decision-making, from a lower middle income country perspective.
AB - INTRODUCTION: There is little available evidence of associations between the
various dimensions of women's empowerment and contraceptive use having been
examined--and of how these associations are mediated by women's socio-economic
and demographic statuses. We assessed these phenomena in Pakistan using a
structured-framework approach. METHODS: We analyzed data on 2,133 women who were
either using any form of contraceptive or living with unmet need for
contraception. The survey was conducted during May - June 2012, with married
women of reproductive age (15-49 years) in three districts of Punjab. The
dimensions of empowerment were categorized broadly into: economic decision
making, household decision-making, and women's mobility. Two measures were
created for each dimension, and for the overall empowerment: women's independent
decisions, and those taken jointly by couples. Contraceptive use was categorized
as either female-only or couple methods on the basis of whether a method requires
the awareness of, or some support and cooperation from, the husband. Multinomial
regression was used, by means of Odds Ratios (OR), to assess associations between
empowerment dimensions and female-only and couple contraceptive methods. RESULTS:
Overall, women tend to get higher decision-making power with increased age,
higher literacy, a greater number of children, or being in a household that has
superior socio-economic status. The measures for couples' decision-making for
overall empowerment and for each dimension of it showed positive associations
with couple methods as well as with female-only methods. The only exception was
the measure of economic empowerment, which was associated only with the couple
method. CONCLUSION: Couples' joint decision-making is a stronger determinant of
the use of contraceptive methods than women-only decision-making. This is the
case over and above the contribution of women's socio-demographic and economic
statuses. Effort needs to be made to educate women and their husbands equally,
with particular focus on highly effective contraceptive methods.
PMID- 25119726
TI - Simultaneous measurement of smoothened entry into and exit from the primary
cilium.
AB - Ciliary accumulation of signaling proteins must result from a rate of ciliary
entry that exceeds ciliary exit, but approaches for distinguishing ciliary entry
vs. exit are lacking. Using a photoconvertible fluorescent protein tag, we
establish an assay that allows a separate but simultaneous examination of ciliary
entry and exit of the Hedgehog signaling protein Smoothened in individual cells.
We show that KAAD-cyclopamine selectively blocks entry, whereas ciliobrevin
interferes initially with exit and eventually with both entry and exit of ciliary
Smoothened. Our study provides an approach to understanding regulation of ciliary
entry vs. exit of Hedgehog signaling components as well as other ciliary
proteins.
PMID- 25119729
TI - Peer influences on internalizing and externalizing problems among adolescents: a
longitudinal social network analysis.
AB - Adolescents who like each other may become more similar to each other with regard
to internalizing and externalizing problems, though it is not yet clear which
social mechanisms explain these similarities. In this longitudinal study, we
analyzed four mechanisms that may explain similarity in adolescent peer networks
with regard to externalizing and internalizing problems: selection,
socialization, avoidance and withdrawal. At three moments during one school-year,
we asked 542 adolescents (8th grade, M-age = 13.3 years, 51 % female) to report
who they liked in their classroom, and their own internalizing and externalizing
problems. Adolescents tend to prefer peers who have similar externalizing problem
scores, but no significant selection effect was found for internalizing problems.
Adolescents who share the same group of friends socialize each other and then
become more similar with respect to externalizing problems, but not with respect
to internalizing problems. We found no significant effects for avoidance or
withdrawal. Adolescents may choose to belong to a peer group that is similar to
them in terms of externalizing problem behaviors, and through peer group
socialization (e.g., enticing, modelling, mimicking, and peer pressure) become
more similar to that group over time.
PMID- 25119730
TI - The effect of seasonality on the structure of rotifers in a black-water shallow
lake in Central Amazonia.
AB - Rotifers have often been used as indicators of sudden changes in physical and
chemical features of the aquatic environment. Such features vary greatly during
flood pulse events in small lakes connected to major floodplains. However, few
are the studies that investigate the consequences of the flood pulse in rotifer
species composition, abundance, richness and diversity, especially in Amazonian
lakes. We analyzed samples from a small blackwater lake of an "igarape" connected
permanently to the Negro river, in Central Amazonia. Samples were taken twice a
year for two years, comprising flooding and receding periods of the flood pulse.
Rotifer abundance increased significantly after draught events, and electrical
conductivity and turbidity were intrinsically related to such variation. Species
composition also changed from flooding to receding periods. Some taxa, such as
Brachionus zahniseri reductus and Lecane remanei were restricted to receding
periods, while Brachionus zahniseri, Brachionus gillardi and Lecane proiecta were
only present during flooding. A shift in the composition of rotifer families was
observed from one period to another, showing the effect of renewing waters of the
flood pulse. These results suggest that the flood pulse acts as a driving force
and stressing condition, considerably altering rotifer community dynamics, either
changing species composition or decreasing abundance.
PMID- 25119731
TI - Reproduction of a whiptail lizard (Ameivula ocellifera, Teiidae) from a coastal
area in northeastern Brazil.
AB - The reproductive ecology of Ameivula ocellifera was studied from September 2009
to August 2010 in a coastal area of the state of Ceara, Brazil. Females
reproduced continuously throughout the year, with a peak at the end of the rainy
season. Even though there was a predominance of pre-reproductive individuals in
the sample, gonadal activity of males peaked synchronously to female
reproduction. Mean clutch size was 1.98 +/- 0.56 and positively associated with
female body size, while mean egg volume was 510.54 +/- 84.29 mm3 and unrelated to
female body size. We did not find any association between clutch size and average
egg volume.
PMID- 25119733
TI - Richness, composition and trophic groups of an avian community in the Pernambuco
Endemism Centre, Alagoas, Brazil.
AB - In northeastern Brazil, the reduction of the natural forest cover to a series of
small, isolated fragments has had negative consequences for the local avian
fauna, in particular, a loss of the more specialized species, while the
populations of some generalists have tended to increase. The present study
focuses on the composition and trophic groups of a bird community on a farm in
the northeastern Brazilian state of Alagoas. Monthly surveys were conducted
between November 2008 and October 2009, based on mist-netting and systematic
observations. Overall, 112 species were recorded, of which 76 were associated
with the two forest fragments surveyed, while all the others were observed
exclusively in the surrounding matrix of pasture and orchards. The bird community
presented a predominance of insectivorous species, followed by omnivores.
However, specialized trunk-creeping and understory insectivores accounted for
only around 15% of the species in this feeding category. The reduced diversity of
other guilds and species with more specialized diets, and the complete absence of
sensitive species such as large parrots and raptors, reflects the severe
fragmentation and degradation of the local forests, which has greatly reduced the
availability of dietary resources and breeding sites.
PMID- 25119732
TI - Bark harvesting systems of Drimys brasiliensis Miers in the Brazilian Atlantic
rainforest.
AB - Drimys brasiliensis Miers, locally known as cataia or casca-de-anta, is a native
tree species of the Atlantic Rainforest. Its bark is harvested from natural
populations. This study examined the recovery capacity of the bark of D.
brasiliensis under different bark harvesting methods, as well as the influence of
these approaches on its population dynamics and reproductive biology. While none
of these treatments resulted in changes in phenological behavior or the rate of
increase of diameter at breast height and tree height, the removal of wider bark
strips resulted in lower rates of bark recovery and higher rates of insect attack
and diseases. Accordingly, the results recommend using strips of bark 2 cm wide
and 2 m long, with 4 cm between strips, for effective rates of bark regrowth and
for lower susceptibility to insect attack and diseases. From these studies, we
concluded that D. brasiliensis has a high potential for sustainable management of
its natural populations, demonstrating the possibility of generating an important
supplementary income for farmers and contributing to the use and conservation of
the Atlantic Rainforest.
PMID- 25119734
TI - Feeding and larval growth of an exotic freshwater prawn Macrobrachium equidens
(Decapoda: Palaemonidae), from Northeastern Para, Amazon Region.
AB - In the present study, we carried out experiments on the diet of the freshwater
prawn Macrobrachium equidens. We tested which type of food and which density of
food is suitable for larval development. For the experiment on the type of food,
eight treatments were carried out: (I) starvation, (AL) microalgae, (RO)
rotifers, (AN) Artemia, (RO + AN) rotifers + Artemia, (AL + RO) microalgae +
rotifers, (AL + AN) microalgae + Artemia, (AL + RO + AN) microalgae + rotifers +
Artemia. For the experiment on the density of food, we used the type of food,
which had resulted in a high survival rate in the previous experiment. Three
treatments were carried out: 4, 8 and 16 Artemia nauplii /mL. The rate of feeding
during larval development was observed. The survival, weight and percentage of
juveniles of each feeding experiment were determined. We found that larvae are
carnivores; however, they have requirements with respect to the type of food,
because larvae completed their cycle from the zoeal to the juvenile stage only
when Artemia nauplii were available. We also verified that the larvae feed mainly
during the day-time, and are opportunistic with respect to the density of food
offered.
PMID- 25119735
TI - Regulation of IL-8 promoter activity by verrucarin A in human monocytic THP-1
cells.
AB - Macrocyclic trichothecenes have been frequently detected in fungi in water
damaged buildings and exhibited higher toxicity than the well-studied
trichothecenes; however, the mechanism underlying their toxicity has been poorly
understood. In this study, transcriptional regulation of the cytokine interleukin
(IL)-8 by a macrocyclic trichothecene, verrucarin A (VA), in human monocytic THP
1 cells is reported. Consistent with previous findings, VA was 100-fold more
cytotoxic than deoxynivalenol (DON), while ochratoxin A (OA) was not cytotoxic.
In cells transduced with the wild-type IL-8 promoter luciferase construct, VA
induced a biphasic dose response composed of an upregulation of luciferase
expression at low concentrations of 0.01-1 ng/ml and a downregulation at high
levels of 10 ng/ml and higher. In contrast, DON induced a sigmoid-shaped dose
response with the EC50 of 11.6 ng/ml, while OA did not markedly affect the IL-8
expression. When cells were transduced with IL-8 promoter with a mutation of
transcription factor nuclear factor-kappaB (NF-kappaB)-binding site, VA (1
ng/ml), DON (1000 ng/ml), and tumor necrosis factor (TNF) alpha (20 ng/ml)
induced luciferase expression were impaired. In addition, the NF-kappaB inhibitor
caffeic acid phenethyl ester inhibited VA-, DON-, and TNFalpha-induced luciferase
expression. Mutation of the CCAAT/enhancer-binding protein (CEBP) beta binding
site of the IL-8 promoter affected only DON-, but not VA- and TNFalpha-induced
luciferase expression. Taken together, these results suggested that VA activated
IL-8 promoter via an NF-kappaB-dependent, but not CEBPbeta-dependent, pathway in
human monocytes.
PMID- 25119736
TI - Single-wall carbon nanotubes (SWCNT) induce cytotoxicity and genotoxicity
produced by reactive oxygen species (ROS) generation in phytohemagglutinin (PHA)
stimulated male human peripheral blood lymphocytes.
AB - Single-wall carbon nanotubes (SWCNT) possess a small size, large surface area,
and high reactivity, which enable them to permeate the cytoplasmic or nuclear
membrane and attach to biological molecules. During medical applications, SWNCT
are usually administered intravenously, which enhances interaction with blood
components. Yet despite this exposure potential, safety evaluation studies of
SWCNTs focused on human blood cells are still lacking. Therefore, this study was
undertaken to examine cytotoxicity, genotoxicity, and proinflammatory responses
following SWCNT treatment of phytohemagglutinin (PHA)-stimulated male human
peripheral blood lymphocytes (PBL). SWCNT were found to inhibit cell growth, as
well as to induce DNA breakage, and micronuclei (MN) formation via reactive
oxygen species (ROS) generation. The addition of N-acetylcysteine (NAC) a cell
permeable antioxidant, decreased ROS generation, cytotoxicity, and genotoxicity
produced by SWCNT treatment. In addition, SWCNT induced tumor necrosis factor
(TNF)-alpha release after 24 h, yet this phenomenon was not related to ROS
generation, as antioxidant NAC treatment did not affect increased proinflammatory
cytokine levels in the phytohemagglutinin (PHA)-stimulated male human PBL.
PMID- 25119737
TI - Relationship between hemorrhagic stroke hospitalization and exposure to fine
particulate air pollution in Taipei, Taiwan.
AB - This study was undertaken to determine whether there was a correlation between
fine particle (PM2.5) levels and hospital admissions for hemorrhagic stroke (HS)
in Taipei, Taiwan. Hospital admissions for HS and ambient air pollution data for
Taipei were obtained for the period 2006-2010. The relative risk of hospital
admissions was estimated using a case-crossover approach, controlling for weather
variables, day of the week, seasonality, and long-term time trends. For the
single-pollutant model (without adjustment for other pollutants), increased HS
admissions were significantly associated with PM2.5 levels both on warm days (>23
degrees C) and cool days (<23 degrees C), with an interquartile range rise
associated with a 12% (95% CI = 7-18%) and 4% (95% CI = 0-8%) elevation in
admissions for HS, respectively. In the two-pollutant models, PM2.5 remained
significantly high after inclusion of SO2 or O3 on both warm and cool days. This
study provides evidence that higher levels of PM2.5 increase the risk of hospital
admissions for HS.
PMID- 25119738
TI - The effect of composition, size, and solubility on acute pulmonary injury in rats
following exposure to Mexico city ambient particulate matter samples.
AB - Particulate matter (PM)-associated metals can contribute to adverse
cardiopulmonary effects following exposure to air pollution. The aim of this
study was to investigate how variation in the composition and size of ambient PM
collected from two distinct regions in Mexico City relates to toxicity
differences. Male Wistar Kyoto rats (14 wk) were intratracheally instilled with
chemically characterized PM10 and PM2.5 from the north and PM10 from the south of
Mexico City (3 mg/kg). Both water-soluble and acid-leachable fractions contained
several metals, with levels generally higher in PM10 South. The insoluble and
total, but not soluble, fractions of all PM induced pulmonary damage that was
indicated by significant increases in neutrophilic inflammation, and several lung
injury biomarkers including total protein, albumin, lactate dehydrogenase
activity, and gamma-glutamyl transferase activity 24 and 72 h postexposure. PM10
North and PM2.5 North also significantly decreased levels of the antioxidant
ascorbic acid. Elevation in lung mRNA biomarkers of inflammation (tumor necrosis
factor [TNF]-alpha and macrophage inflammatory protein [MIP]-2), oxidative stress
(heme oxygenase [HO]-1, lectin-like oxidized low-density lipoprotein receptor
[LOX]-1, and inducibile nitric oxide synthase [iNOS]), and thrombosis (tissue
factor [TF] and plasminogen activator inhibitor [PAI]-1), as well as reduced
levels of fibrinolytic protein tissue plasminogen activator (tPA), further
indicated pulmonary injury following PM exposure. These responses were more
pronounced with PM10 South (PM10 South > PM10 North > PM2.5 North), which
contained higher levels of redox-active transition metals that may have
contributed to specific differences in selected lung gene markers. These findings
provide evidence that surface chemistry of the PM core and not the water-soluble
fraction played an important role in regulating in vivo pulmonary toxicity
responses to Mexico City PM.
PMID- 25119739
TI - Toxicity and accumulation of trinitrotoluene (TNT) and its metabolites in
Atlantic salmon alevins exposed to an industrially polluted water.
AB - A pond in an industrial area in Sweden was selected to study adverse effects on
salmon alevins from 2,4,6-trinitrotoluene (TNT)-contaminated water. Chemical
screening revealed heavy contamination of TNT and its degradation products, 2
amino-4,6-dinitrotoluene (2-ADNT) and 4-amino-2,6-dinitrotoluene (4-ADNT),
ranging from 0.05 to 230 g/kg in the sediment (dry weight) within the water
system. Pond water contained 3 mg/L TNT. A dilution series of pond water mixed
with tap water revealed increased death frequency in alevins down to fivefold
dilution (approximate 0.4 mg TNT/L). Uptake was concentration dependent, reaching
7, 9, and 22 MUg/g tissue for TNT, 2-ADNT, and 4-ADNT at the highest test
concentration. A time-dependent uptake of TNT and its degradation products was
found at a water concentration of 0.08 mg TNT/L. Degradation products of TNT
showed a more efficient uptake compared to native TNT, and accumulation of 4-ADNT
was more pronounced during the late phase of the 40-d exposure study.
Bioconcentration factors (BCF) (0.34, 52, and 134 ml/g for TNT, 2-ADNT, and 4
ADNT, respectively) demonstrated a significant uptake of the metabolite 4-ADNT in
alevin tissue. Disturbed physiological conditions and delayed development in
alevins were not studied, but may not be excluded even at 125-fold diluted pond
water (0.016 mg TNT/L). BCF data indicated that bioaccumulation of TNT
metabolites need to be considered in TNT chronic toxicity. Fish species and age
differences in the accumulation of TNT metabolites need to be further studied.
PMID- 25119741
TI - Identification of angiogenesis-related miRNAs in a population of patients with
renal clear cell carcinoma.
AB - In the present study, we compared the expression of miRNAs and angiogenesis
related genes in the renal tumors and adjacent normal renal tissues of patients
with clear cell renal cell carcinoma (ccRCC). The first part of the present study
was a preliminary analysis of 4 patients with stage T1a/b ccRCC that measured the
levels of angiogenesis and expression of angiogenesis-related genes and miRNAs in
the tumors and adjacent normal renal tissues. The second part of this study was
an analysis of 30 patients with stage T1, T2 or T3 ccRCC that employed qPCR to
characterize expression of angiogenesis-related miRNAs in the tumors and adjacent
normal tissues. The first part of this study indicated that all 4 patients had
increased levels of CD34 in tumors, indicating elevated angiogenesis. However,
quantitative analysis of microvessel density and expression of miRNAs indicated
highly variable results among these patients. The data of all patients in the
present study indicated that more patients with stage T1 ccRCC had higher
expression of miR-126 and miR-378 in their normal tissues, whereas more patients
with stage T2/3 ccRCC had higher expression of these miRNAs in their tumor
tissues. The tumors of patients with ccRCC had lower expression of miR-126 and
miR-378 during the early stages of disease (T1), but higher expression of these
miRNAs during the later stages of disease (T2/T3).
PMID- 25119742
TI - MicroRNA-193b is a regulator of amyloid precursor protein in the blood and
cerebrospinal fluid derived exosomal microRNA-193b is a biomarker of Alzheimer's
disease.
AB - Amyloid precursor protein (APP) has an important function in the generation of
Alzheimer's disease (AD). In our previous study, miR-193b was found to be
downregulated in the hippocampi of 9-month-old APP/PS1 double-transgenic mice
using microRNA (miR) array. In the present study, bioinformatic analyses showed
that miR-193b was a miR that was predicted to potentially target the 3'
untranslated region (UTR) of APP. Subsequently, the function of miR-193b on APP
was studied. The levels of miR-193b, exosomal miR-193b, Abeta, tau, p-tau, HCY
and APOE in samples from APP/PS1 double-transgenic mice, mild cognitive
impairment (MCI) and dementia of Alzheimer-type (DAT) patients, were measured.
The results indicated that overexpression of miR-193b could repress the mRNA and
protein expression of APP. The miR-193b inhibitor oligonucleotide induced
upregulation of APP. Binding sites of miR-193b in the 3'-UTR of APP were
identified by luciferase assay. MCI and DAT patients had lower exosomal miR-193b,
but not total miR-193b, in the blood as compared with the controls. DAT patients
had lower exosomal miR-193b levels in blood as compared with the MCI group. A
decreased exosomal miR-193b expression level was additionally observed in the
cerebral spinal fluid (CSF) of DAT patients. Negative correlations were found
between exosomal miR-193b and Abeta42 in the CSF of DAT patients. In conclusion,
these findings showed that miR-193b may function in the development of AD and
exosomal miR-193b has potential as a novel, non-invasive, blood-based biomarker
of MCI and DAT patients.
PMID- 25119743
TI - Immunoprophylaxis against respiratory syncytial virus with palvizumab: what is
new?
PMID- 25119744
TI - Respiratory infections in children up to two years of age on prophylaxis with
palivizumab.
AB - OBJECTIVE: To identify the viruses involved in acute respiratory tract infections
and to analyze the rates of hospitalization and death in children on palivizumab
prophylaxis. METHODS: Prospective cohort of 198 infants up to one year old who
were born before 29 weeks of gestational age and infants under two years old with
hemodynamically unstable cardiopathy or chronic pulmonary disease who received
prophylactic palivizumab against severe respiratory syncytial virus infections in
2008. During the study period, in each episode of acute respiratory tract
infection, nasopharyngeal aspirate was collected to identify respiratory
syncytial virus, adenovirus, parainfluenza 1, 2 and 3, influenza A and B by
direct immunofluorescence, rhinovirus and metapneumovirus by polymerase chain
reaction preceded by reverse transcription. Data regarding hospitalization and
deaths were monitored. RESULTS: Among the 198 studied infants, 117 (59.1%)
presented acute respiratory tract infections, with a total of 175 episodes. Of
the 76 nasopharyngeal aspirates collected during respiratory tract infections, 37
were positive, as follow: rhinovirus (75.7%), respiratory syncytial virus
(18.9%), parainfluenza (8.1%), adenovirus 2 (2.7%), metapneumovirus (2.7%) and
three samples presented multiple agents. Of the 198 children, 48 (24.4%) were
hospitalized: 30 (15.2%) for non-infectious etiology and 18 (9.1%) for
respiratory causes. Among these 18 children, one case of respiratory syncytial
virus was identified. Two deaths were reported, but respiratory syncytial virus
was not identified. CONCLUSIONS: During the prophylaxis period, low frequency of
respiratory syncytial virus infections and low rates of hospitalization were
observed, suggesting the benefit of palivizumab prophylaxis.
PMID- 25119745
TI - Prevalence and profile of congenital heart disease and pulmonary hypertension in
Down syndrome in a pediatric cardiology service.
AB - OBJECTIVE: To determine the frequence and profile of congenital heart defects in
Down syndrome patients referred to a pediatric cardiologic center, considering
the age of referral, gender, type of heart disease diagnosed by transthoracic
echocardiography and its association with pulmonary hypertension at the initial
diagnosis. METHODS: Cross-sectional study with retrospective data collection of
138 patients with Down syndrome from a total of 17,873 records. Descriptive
analysis of the data was performed, using Epi-Info version 7. RESULTS: Among the
138 patients with Down syndrome, females prevailed (56.1%) and 112 (81.2%) were
diagnosed with congenital heart disease. The most common lesion was ostium
secundum atrial septal defect, present in 51.8%, followed by atrioventricular
septal defect, in 46.4%. Ventricular septal defects were present in 27.7%, while
tetralogy of Fallot represented 6.3% of the cases. Other cardiac malformations
corresponded to 12.5%. Pulmonary hypertension was associated with 37.5% of the
heart diseases. Only 35.5% of the patients were referred before six months of
age. CONCLUSIONS: The low percentage of referral until six months of age
highlights the need for a better tracking of patients with Down syndrome in the
context of congenital heart disease, due to the high frequency and progression of
pulmonary hypertension.
PMID- 25119746
TI - Estimating outcomes in newborn infants using fuzzy logic.
AB - OBJECTIVE: To build a linguistic model using the properties of fuzzy logic to
estimate the risk of death of neonates admitted to a Neonatal Intensive Care
Unit. METHODS: Computational model using fuzzy logic. The input variables of the
model were birth weight, gestational age, 5th-minute Apgar score and inspired
fraction of oxygen in newborn infants admitted to a Neonatal Intensive Care Unit
of Taubate, Southeast Brazil. The output variable was the risk of death,
estimated as a percentage. Three membership functions related to birth weight,
gestational age and 5th-minute Apgar score were built, as well as two functions
related to the inspired fraction of oxygen; the risk presented five membership
functions. The model was developed using the Mandani inference by means of
Matlab(r) software. The model values were compared with those provided by experts
and their performance was estimated by ROC curve. RESULTS: 100 newborns were
included, and eight of them died. The model estimated an average possibility of
death of 49.7+/-29.3%, and the possibility of hospital discharge was 24+/-17.5%.
These values are different when compared by Student's t-test (p<0.001). The
correlation test revealed r=0.80 and the performance of the model was 81.9%.
CONCLUSIONS: This predictive, non-invasive and low cost model showed a good
accuracy and can be applied in neonatal care, given the easiness of its use.
PMID- 25119747
TI - Preterm newborns at Kangaroo Mother Care: a cohort follow-up from birth to six
months.
AB - OBJECTIVE: To evaluate clinical outcomes, growth and exclusive breastfeeding
rates in premature infants assisted by Kangaroo Mother Care at birth, at
discharge and at six months of life. METHODS: Prospective study of a premature
infants cohort assisted by Kangaroo Mother Care in a tertiary public maternity in
Northeast Brazil with birth weight <=1750g and with clinical conditions for
Kangaroo care. RESULTS: The sample was composed by 137 premature infants, being
62.8% female, with average birth weight of 1365+/-283g, average gestational age
of 32+/-3 weeks and 26.2% were adequate for gestational age. They have been
admitted in the Kangaroo Ward with a median of 13 days of life, weighing 1430+/
167g and, at this time, 57.7% were classified as small for corrected gestational
age. They were discharged with 36.8+/-21.8 days of chronological age, weighing
1780+/-165g and 67.9% were small for corrected gestational age. At six months of
life (n=76), they had an average weight of 5954+/-971g, and 68.4% presented
corrected weight for gestational age between percentiles 15 and 85 of the World
Health Organization (WHO) weight curve. Exclusive breastfeeding rate at discharge
was 56.2% and, at six months of life, 14.4%. CONCLUSIONS: In the studied sample,
almost two thirds of the children assisted by Kangaroo Mother Care were, at six
months of life, between percentiles 15 and 85 of the WHO weight curves. The
frequency of exclusive breastfeeding at six months was low.
PMID- 25119748
TI - Alpha-tocopherol concentration in serum and colostrum of mothers with gestational
diabetes mellitus.
AB - OBJECTIVE: To evaluate and compare the levels of alpha-tocopherol in colostrum
and in the serum of healthy and diabetic mothers. METHODS: This cross-sectional
study enrolled 51 volunteer mothers, 20 with the diagnosis of gestational
diabetes mellitus and 31 without associated diseases. Serum and colostrum samples
were collected in fasting in the immediate postpartum period and alpha-tocopherol
was analyzed by high performance liquid chromatography (HPLC). In order to define
the nutritional status of vitamin E, the cutoff point for the serum (697.7ug/dL)
was adopted. Student's t-test for independent variables compared the average
concentrations of alpha-tocopherol in the serum and in the colostrum between
control and gestational diabetes mellitus groups. Pearson's correlation was used
to assess the relationship between the concentration of alpha-tocopherol in serum
and colostrum for both groups. Differences were considered significant when
p<0.05. RESULTS: The alpha-tocopherol concentration in colostrum was 1,483.1+/
533.8ug/dL for Control Group and 1,368.8+/-681.8ug/dL for diabetic women, without
differences between groups (p=0.50). However, alpha-tocopherol concentration in
the serum was 1,059.5+/-372.7ug/dL in the Control Group and 1,391.4+/-531.5ug/dL
in the diabetic one (p<0.01). No correlation was found between the concentration
of alpha-tocopherol in the serum and in the colostrum for control and diabetic
groups. CONCLUSIONS: The groups had adequate nutritional status of vitamin E.
Gestational diabetes was not associated with changes in alpha-tocopherol
concentration in colostrum.
PMID- 25119749
TI - Pediatrician's knowledge on the management of the infant who cries excessively in
the first months of life.
AB - OBJECTIVE: To evaluate the attitude, the practice and the knowledge of
pediatricians regarding the management of the infant who cries excessively in the
first months of life. METHODS: Descriptive cross-sectional study that enrolled
pediatricians (n=132) randomly interviewed at a Pediatric meeting in Brazil, in
August 2012. The data were collected by a self-administered standardized form
after reading the hypothetical case of an infant who cried excessively. RESULTS:
The majority of the participants were females, the mean age was 39 years and the
average mean time working in the specialty was 14 years; 52.2% were Board
Certified by the Brazilian Society of Pediatrics. The diagnosis most often
considered was gastroesophageal reflux disease (62.9%), followed by infant colic
(23.5%) and cow's milk allergy (6.8%). The diagnostic test most frequently
mentioned was 24-hour esophageal pH-monitoring (21.9%). The medications most
frequently indicated were domperidone (30.3%), the combination of domperidone
with ranitidine (12.1%) and paracetamol (6%). CONCLUSIONS: In the approach of the
infant who cries excessively, diagnostic tests are frequently requested and
unnecessary medical treatment is usually recommended.
PMID- 25119750
TI - Intake of protein, calcium and sodium in public child day care centers.
AB - OBJECTIVE: To assess calcium, protein and sodium intake, of children that attend
public day-care centers and to compare it with the recommended one. METHODS:
Cross-sectional descriptive study in seven public day care centers of Sao Paulo
city, Southeast Brazil, which enrolled 366 children between 12 and 36 months of
age. The data collection occurred between September and December 2010. Each day
care center was evaluated for three non-consecutive days, totaling 42 days and
210 meals. Dietary intake was assessed by a direct food weighing method. For the
nutritional calculation, DietWin(r) Profissional 2.0 was used, and the adequacy
was calculated according to the recommendations of the National School Feeding
Program for energy, protein, calcium and sodium. The calcium/protein relation was
also calculated, as well as calcium density (mg/1,000kcal). RESULTS: The energy
(406.4kcal), protein (18.2g) and calcium (207.6mg) consumption did not reach the
recommended values in all the evaluated day care centers. Sodium intake exceeded
up to three times the recommendation. The calcium/protein ratio of 11.7mg/g was
less than the adequate one (20mg/g). CONCLUSIONS: There was inadequacy of
calcium, protein and sodium dietary intake, in children attending public day-care
centers.
PMID- 25119751
TI - Prevalence of weight excess according to age group in students from Campinas, SP,
Brazil.
AB - OBJECTIVE: To evaluate the prevalence of weight excess in children and
adolescents attending public and private schools of Campinas, Southeast Brazil,
according to age group. METHODS: Cross-sectional study that enrolled 3,130
students from 2010 to 2012. The weight and the height were measured and the body
mass index (BMI) was calculated. The students were classified by BMI Z-score/age
curves of the World Health Organization (WHO)-2007 (thinness, normal weight,
overweight and obesity) and by age group (7-10, 11-14 and 15-18 years).
Multinomial logistic regression analysis was applied to verify variables
associated to overweight and obesity. RESULTS: Among the 3,130 students, 53.7%
attended public schools and 53.4% were girls. The prevalence of weight excess
(overweight or obesity) was higher in private schools (37.3%) than in public ones
(32.9%) and among males (37.5%), compared to females (32.7%; p<0.05). The chance
of having weight excess in children aged 7-10 years was more than twice of those
over 15 years old (OR 2.4; 95%CI 2.0-3.0) and it was 60% higher for the group
with 11-14 years old (OR 1.6; 95%CI 1.3-2.0). The chance of being obese was three
times higher in 7-10 years old children than in the adolescents with 15-18 years
old (OR 4.4; 95%CI 3.3-6.4) and 130% higher than the group with 11-14 years old
(OR 2.3; 95%CI 1.6-3.2). CONCLUSIONS: The prevalence of weight excess in Campinas
keeps increasing at an alarming rate, especially in the younger age group.
PMID- 25119752
TI - Body composition and risk for metabolic alterations in female adolescents.
AB - OBJECTIVE: To study anthropometrical and body composition variables as predictors
of risk for metabolic alterations and metabolic syndrome in female adolescents.
METHODS: Biochemical, clinical and corporal composition data of 100 adolescents
from 14 to 17 years old, who attended public schools in Vicosa, Southeastern
Brazil, were collected. RESULTS: Regarding nutritional status, 83, 11 and 6%
showed eutrophia, overweight/obesity and low weight, respectively, and 61%
presented high body fat percent. Total cholesterol presented the highest
percentage of inadequacy (57%), followed by high-density lipoprotein (HDL - 50%),
low-density lipoprotein (LDL - 47%) and triacylglycerol (22%). Inadequacy was
observed in 11, 9, 3 and 4% in relation to insulin resistance, fasting insulin,
blood pressure and glycemia, respectively. The highest values of the fasting
insulin and the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) were
verified at the highest quartiles of body mass index (BMI), waist perimeter,
waist-to-height ratio and body fat percent. Body mass index, waist perimeter, and
waist-to-height ratio were the better predictors for high levels of HOMA-IR,
blood glucose and fasting insulin. Waist-to-hip ratio was associated to arterial
hypertension diagnosis. All body composition variables were effective in
metabolic syndrome diagnosis. CONCLUSIONS: Waist perimeter, BMI and waist-to
height ratio showed to be good predictors for metabolic alterations in female
adolescents and then should be used together for the nutritional assessment in
this age range.
PMID- 25119753
TI - Assessment of calcium intake by adolescents.
AB - OBJECTIVE: To evaluate the daily calcium intake of adolescents in schools from
Chapeco, Santa Catarina, Southern Brazil, to check if calcium intake is in
accordance with the Dietary Reference Intakes (DRI), and to investigate variables
associated with daily calcium intake. METHODS: Cross-sectional study approved by
the Institutional Review Board and developed in 2010. Students of the 8th grade
completed questionnaires with personal data and questions about the calcium-rich
foods intake frequency. In order to compare students with adequate (1300mg) or
inadequate intake of calcium/day (<1300mg), parametric and nonparametric tests
were used. RESULTS: A total of 214 students with a mean age of 14.3+/-1.0 years
were enrolled. The median daily calcium intake was 540mg (interquartile range -
IQ: 312-829mg) and only 25 students (11.7%) had calcium intake within the
recommendations of the DRI for age. Soft drink consumption >=3 times/week was
associated with a lower intake of calcium. CONCLUSIONS: Few students ingested
adequate levels of calcium for the age group. It is necessary to develop a
program to encourage a greater intake of calcium-rich foods in adolescence.
PMID- 25119754
TI - Neck circumference as a new anthropometric indicator for prediction of insulin
resistance and components of metabolic syndrome in adolescents: Brazilian
Metabolic Syndrome Study.
AB - OBJECTIVE: To evaluate the correlation between neck circumference and insulin
resistance and components of metabolic syndrome in adolescents with different
adiposity levels and pubertal stages, as well as to determine the usefulness of
neck circumference to predict insulin resistance in adolescents. METHODS: Cross
sectional study with 388 adolescents of both genders from ten to 19 years old.
The adolescents underwent anthropometric and body composition assessment,
including neck and waist circumferences, and biochemical evaluation. The pubertal
stage was obtained by self-assessment, and the blood pressure, by auscultation.
Insulin resistance was evaluated by the Homeostasis Model Assessment-Insulin
Resistance. The correlation between two variables was evaluated by partial
correlation coefficient adjusted for the percentage of body fat and pubertal
stage. The performance of neck circumference to identify insulin resistance was
tested by Receiver Operating Characteristic Curve. RESULTS: After the adjustment
for percentage body fat and pubertal stage, neck circumference correlated with
waist circumference, blood pressure, triglycerides and markers of insulin
resistance in both genders. CONCLUSIONS: The results showed that the neck
circumference is a useful tool for the detection of insulin resistance and
changes in the indicators of metabolic syndrome in adolescents. The easiness of
application and low cost of this measure may allow its use in Public Health
services.
PMID- 25119755
TI - Biochemical, anthropometric and body composition indicators as predictors of
hepatic steatosis in obese adolescents.
AB - OBJECTIVE: To describe the prevalence of hepatic steatosis and to assess the
performance of biochemical, anthropometric and body composition indicators for
hepatic steatosis in obese teenagers. METHODS: Cross-sectional study including 79
adolecents aged from ten to 18 years old. Hepatic steatosis was diagnosed by
abdominal ultrasound in case of moderate or intense hepatorenal contrast and/or a
difference in the histogram >=7 on the right kidney cortex. The insulin
resistance was determined by the Homeostasis Model Assessment-Insulin Resistance
(HOMA-IR) index for values >3.16. Anthropometric and body composition indicators
consisted of body mass index, body fat percentage, abdominal circumference and
subcutaneous fat. Fasting glycemia and insulin, lipid profile and hepatic
enzymes, such as aspartate aminotransferase, alanine aminotransferase, gamma
glutamyltransferase and alkaline phosphatase, were also evaluated. In order to
assess the performance of these indicators in the diagnosis of hepatic steatosis
in teenagers, a ROC curve analysis was applied. RESULTS: Hepatic steatosis was
found in 20% of the patients and insulin resistance, in 29%. Gamma
glutamyltransferase and HOMA-IR were good indicators for predicting hepatic
steatosis, with a cutoff of 1.06 times above the reference value for gamma
glutamyltransferase and 3.28 times for the HOMA-IR. The anthropometric
indicators, the body fat percentage, the lipid profile, the glycemia and the
aspartate aminotransferase did not present significant associations. CONCLUSIONS:
Patients with high gamma-glutamyltransferase level and/or HOMA-IR should be
submitted to abdominal ultrasound examination due to the increased chance of
having hepatic steatosis.
PMID- 25119756
TI - Associated factors of overweight in adolescents from public schools in Northern
Minas Gerais State, Brazil.
AB - OBJECTIVE: In order to support plans and actions that combat the local increasing
overweight and obesity prevalence in adolescents, the factors associated to
weight excess in public school students from Montes Claros, MG, Southeast Brazil,
were studied. METHODS: Cross-sectional study with a sample of adolescents from
the public schools of the city. The nutritional status was evaluated and an
inquiry was carried out in the schools to determine food consumption and practice
of physical activities. Factors associated to weight excess were assessed by
bivariate analysis followed by logistic regression. RESULTS: Weight excess
prevalence was detected in 18.5% of the 535 adolescents evaluated. The factors
associated to weight excess were: per capita income above half minimum wage (OR
1.99; 95%CI 1.01-3.93), candy consumption above two daily portions (OR 1.94;
95%CI 1.13-3.32) and absence of sport activity during leisure time (OR 2.54;
95%CI 1.15-5.59). CONCLUSIONS: The proportion of weight excess in adolescents
from public schools is relevant and associated with socioeconomic condition of
the family, bad eating habits and sedentary life.
PMID- 25119757
TI - Cardiac autonomic dysfunction in obese normotensive children and adolescents.
AB - OBJECTIVE: To test the hypothesis that obese normotensive children and
adolescents present impaired cardiac autonomic control compared to non-obese
normotensive ones. METHODS: For this cross-sectional study, 66 children and
adolescents were divided into the following groups: Obese (n=31, 12+/-3 years
old) and Non-Obese (n=35, 13+/-3 years old). Obesity was defined as body mass
index greater than the 95th percentile for age and gender. Blood pressure was
measured by oscillometric method after 15 minutes of rest in supine position. The
heart rate was continuously registered during ten minutes in the supine position
with spontaneous breathing. The cardiac autonomic control was assessed by heart
rate variability, which was calculated from the five-minute minor variance of the
signal. The derivations were the index that indicates the proportion of the
number of times in which normal adjacent R-R intervals present differences >50
miliseconds (pNN50), for the time domain, and, for the spectral analysis, low
(LF) and high frequency (HF) bands, besides the low and high frequencies ratio
(LF/HF). The results were expressed as mean+/-standard deviation and compared by
Student's t-test or Mann-Whitney's U-test. RESULTS: Systolic blood pressure
(116+/-14 versus 114+/-13mmHg, p=0.693) and diastolic blood pressure (59+/-8
versus 60+/-11mmHg, p=0.458) were similar between the Obese and Non-Obese groups.
The pNN50 index (29+/-21 versus 43+/-23, p=0.015) and HF band (54+/-20 versus
64+/-14 normalized units - n.u., p=0.023) were lower in the Obese Group. The LF
band (46+/-20 versus 36+/-14 n.u., p=0.023) and LF/HF ratio (1.3+/-1.6 versus
0.7+/-0.4, p=0.044) were higher in Obese Group. CONCLUSIONS: Obese normotensive
children and adolescents present impairment of cardiac autonomic control.
PMID- 25119758
TI - Assessment of respiratory muscle strength in children according to the
classification of body mass index.
AB - OBJECTIVE: To assess and compare the respiratory muscle strength among eutrophic,
overweight and obese school children, as well as to identify anthropometric and
respiratory variables related to the results. METHODS: Cross-sectional survey
with healthy schoolchildren aged 7-9 years old, divided into three groups: Normal
weight, Overweight and Obese. The International Study of Asthma and Allergies in
Childhood (ISAAC) questionnaire was applied. The body mass index (BMI) was
evaluated, as well as the forced expiratory volume in one second (FEV1) with a
portable digital device. The maximal inspiratory and expiratory pressures (MIP
and MEP) were measured by a digital manometer. Comparisons between the groups
were made by Kruskal-Wallis test. Spearman's correlation coefficient was used to
analyze the correlations among the variables. RESULTS: MIP of eutrophic school
children was higher than MIP found in overweight (p=0.043) and obese (p=0.013)
children. MIP was correlated with BMI percentile and weight classification (r=
0.214 and r=-0.256) and MEP was correlated with height (r=0.328). Both pressures
showed strong correlation with each other in all analyses (r>=0.773), and less
correlation with FEV1 (MIP - r=0.362 and MEP - r=0.494). FEV1 correlated with MEP
in all groups (r: 0.429 - 0.569) and with MIP in Obese Group (r=0.565). Age was
correlated with FEV1 (r=0.578), MIP (r=0.281) and MEP (r=0.328). CONCLUSIONS:
Overweight and obese children showed lower MIP values, compared to eutrophic
ones. The findings point to the influence of anthropometric variables on
respiratory muscle strength in children.
PMID- 25119759
TI - Prevalence of headache and its interference in the activities of daily living in
female adolescent students.
AB - OBJECTIVE: To describe the prevalence of headache and its interference in the
activities of daily living (ADL) in female adolescent students. METHODS: This
descriptive cross-sectional study enrolled 228 female adolescents from a public
school in the city of Petrolina, Pernambuco, Northeast Brazil, aged ten to 19
years. A self-administered structured questionnaire about socio-demographic
characteristics, occurrence of headache and its characteristics was employed.
Headaches were classified according to the International Headache Society
criteria. The chi-square test was used to verify possible associations, being
significant p<0.05. RESULTS: After the exclusion of 24 questionnaires that did
not met the inclusion criteria, 204 questionnaires were analyzed. The mean age of
the adolescents was 14.0+/-1.4 years. The prevalence of headache was 87.7%. Of
the adolescents with headache, 0.5% presented migraine without pure menstrual
aura; 6.7%, migraine without aura related to menstruation; 1.6%, non-menstrual
migraine without aura; 11.7%, tension-type headache and 79.3%, other headaches.
Significant associations were found between pain intensity and the following
variables: absenteeism (p=0.001); interference in ADL (p<0.001); medication use
(p<0.001); age (p=0.045) and seek for medical care (p<0.022). CONCLUSIONS: The
prevalence of headache in female adolescents observed in this study was high,
with a negative impact in ADL and school attendance.
PMID- 25119760
TI - Congenital heart disease and chromossomopathies detected by the karyotype.
AB - OBJECTIVE: To review the relationship between congenital heart defects and
chromosomal abnormalities detected by the karyotype. DATA SOURCES: Scientific
articles were searched in MEDLINE database, using the descriptors "karyotype" OR
"chromosomal" OR "chromosome" AND "heart defects, congenital". The research was
limited to articles published in English from 1980 on. DATA SYNTHESIS: Congenital
heart disease is characterized by an etiologically heterogeneous and not well
understood group of lesions. Several researchers have evaluated the presence of
chromosomal abnormalities detected by the karyotype in patients with congenital
heart disease. However, most of the articles were retrospective studies developed
in Europe and only some of the studied patients had a karyotype exam. In this
review, only one study was conducted in Latin America, in Brazil. It is known
that chromosomal abnormalities are frequent, being present in about one in every
ten patients with congenital heart disease. Among the karyotype alterations in
these patients, the most important is the trisomy 21 (Down syndrome). These
patients often have associated extra-cardiac malformations, with a higher risk of
morbidity and mortality, which makes heart surgery even more risky. CONCLUSIONS:
Despite all the progress made in recent decades in the field of cytogenetic, the
karyotype remains an essential tool in order to evaluate patients with congenital
heart disease. The detailed dysmorphological physical examination is of great
importance to indicate the need of a karyotype.
PMID- 25119761
TI - Tools used for evaluation of Brazilian children's quality of life.
AB - OBJECTIVE: To review the available tools to evaluate children's quality of life
validated for Brazilian language and culture. DATA SOURCES: Search of scientific
articles in Medline, Lilacs and SciELO databases using the combination of
descriptors "quality of life", "child" and "questionnaires" in Portuguese and
English. DATA SYNTHESIS: Among the tools designed to assess children's quality of
life validated for the Brazilian language and culture, the Auto questionnaire
Qualite de Vie Enfant Image (AUQEI), the Child Health Questionnaire - Parent Form
50 (CHQ-PF50), the Pediatric Quality of Life Inventory (PedsQL(tm)) version 4.0
and the Kidscreen-52 are highlighted. Some tools do not include all range of ages
and some lack domains that are currently considered relevant in the context of
childhood, such as bullying. Moreover, due to the cultural diversity of Brazil,
it may be necessary to adapt some instruments or to validate other tools.
CONCLUSIONS: There are validated instruments to evaluate children's quality of
life in Brazil. However, the validation or the adaptation of other international
tools have to be considered in order to overcome current deficiencies.
PMID- 25119762
TI - Heart rate variability in children with type 1 diabetes mellitus.
AB - OBJECTIVE: To gather current information about the effects of type 1 diabetes
mellitus on children's cardiac autonomic behavior. DATA SOURCES: The search of
articles was conducted on PubMed, Ibecs, Medline, Cochrane, Lilacs, SciELO and
PEDro databases using the MeSH terms: "autonomic nervous system", "diabetes
mellitus", "child", "type 1 diabetes mellitus", "sympathetic nervous system" and
"parasympathetic nervous system", and their respective versions in Portuguese
(DeCS). Articles published from January 2003 to February 2013 that enrolled
children with 9-12 years old with type 1 diabetes mellitus were included in the
review. DATA SYNTHESIS: The electronic search resulted in four articles that
approached the heart rate variability in children with type 1 diabetes mellitus,
showing that, in general, these children present decreased global heart rate
variability and vagal activity. The practice of physical activity promoted
benefits for these individuals. CONCLUSIONS: Children with type 1 diabetes
mellitus present changes on autonomic modulation, indicating the need for early
attention to avoid future complications in this group.
PMID- 25119764
TI - Let's reduce the blood volume collected for laboratorial exams?
PMID- 25119763
TI - Genitalia burn: accident or violence? Concerns that transcend injury treatment.
AB - OBJECTIVE: To describe a case of genital burn which raised the suspicion of
maltreatment (sexual abuse and neglect by lack of supervision). CASE DESCRIPTION:
An infant was taken to the Emergency Room of a pediatric hospital with an
extensive burn in the vulva and perineum. The mother claimed the burn had been
caused by a sodium-hydroxide-based product. However, the injury severity led to
the suspicion of sexual abuse, which was then ruled out by a multidisciplinary
team, based on the consistent report by the mother. Besides, the lesion type
matched those caused by the chemical agent involved in the accident and the
family context was evaluated and considered adequate. The patient had a favorable
outcome and was discharged after four days of hospitalization. Outpatient follow
up during six months after the accident enabled the team to rule out neglect by
lack of supervision. COMMENTS: Accidents and violence are frequent causes of
physical injuries in children, and the differential diagnosis between them can be
a challenge for healthcare workers, especially in rare clinical conditions
involving patients who cannot speak for themselves. The involvement of a
multidisciplinary trained team helps to have an adequate approach, ensuring child
protection and developing a bond with the family; the latter is essential for a
continued patient follow-up.
PMID- 25119775
TI - An organic hydrophilic dye for water-based dye-sensitized solar cells.
AB - In this study we report the first organic hydrophilic dye employed for 100% water
based electrolyte DSSCs. We show that the replacement of alkyl by glycolic chains
in the dye structure is able to provide excellent wettability, resulting in an
efficient system with remarkably reduced desorption problems that allowed us to
perform tests over a wide pH range. By changing the electrolyte composition,
employing chenodeoxycholic acid as a co-adsorbent and using PEDOT counter
electrodes, 3% power conversion efficiency under 1-sun illumination was obtained.
We show that chenodeoxycholic acid does not significantly increase the
wettability, and we provide new insights into the higher performance resulting
from its co-adsorption.
PMID- 25119777
TI - Association Between Serum Amyloid-Beta and Renal Functions: Implications for
Roles of Kidney in Amyloid-Beta Clearance.
AB - Amyloid-beta (Abeta) plays a central role in the pathogenesis of Alzheimer's
disease (AD), and it is a major therapeutic target for AD. It is proposed that
removal of Abeta in blood can facilitate Abeta clearance from the brain,
representing a promising therapeutic approach for AD. However, the efficacy and
mechanisms for Abeta clearance by peripheral organs and tissues remain largely
unknown. In the present study, 47 chronic kidney disease (CKD) patients (16 newly
diagnosed patients who had never been dialyzed and 31 patients who were receiving
dialysis) and 43 normal controls (NC) were enrolled. We found that serum Abeta
levels were significantly higher in CKD patients than NC. CKD patients who were
receiving dialysis had lower serum Abeta levels than patients without receiving
dialysis, being comparable to NC. Furthermore, serum Abeta levels were correlated
with renal functions reflected by estimated glomerular filtration rate (eGFR) and
residual GFR (rGFR). Our study suggests that kidney is involved in peripheral
clearance of Abeta, and dialysis might be a potential therapeutic approach of
Abeta removal.
PMID- 25119778
TI - The case for extracellular Nm23-H1 as a driver of acute myeloid leukaemia (AML)
progression.
AB - Studies in the 1990s identified a link between extracellular Nm23 proteins and
acute myeloid leukaemia (AML). Confidence in the importance of these observations
was undermined by a lack of appreciation that extracellular Nm23 proteins were
relevant to either normal or pathophysiology coupled with the lack of
demonstrable activity of Nm23 proteins against human AML cell lines. However,
independent studies have highlighted the importance of Nm23-H1 in AML and have
identified an elaborate Nm23-H1-mediated cross talk between cells within the AML
clone. In other studies, roles for Nm23-H1 have now also been implicated in the
maintenance of the stem cell state of embryonic stem (ES) cells and induced
pluripotent stem (IPS) cells. In this review, we have generated a unifying model
of the action of Nm23-H1 in AML, including previously unpublished data from our
laboratory, and provide arguments as to why we consider this role to be distinct
from that in ES and IPS cells.
PMID- 25119780
TI - A Cross-sectional Analysis Investigating Organizational Factors That Influence
Near-Miss Error Reporting Among Hospital Pharmacists.
AB - OBJECTIVE: Underreporting near-miss errors undermines hospitals' ability to
improve patient safety. The objective of this analysis was to determine the
extent to which punitive work climate, inadequate error feedback to staff, or
insufficient preventative procedures are associated with decreased frequency of
near-miss error reporting among hospital pharmacists. METHODS: Survey data were
obtained from the Agency of Healthcare Research and Quality 2010 Hospital Survey
on Patient Safety Culture. Near-miss error reporting was defined using a Likert
scale response to the question, "When a mistake is made, but is caught and
corrected before affecting the patient, how often is this reported?" Work
climate, error feedback to staff, and preventative procedures were defined
similarly using responses to survey questions. Multivariate ordinal regressions
estimated the likelihood of agreeing that near-miss errors were rarely reported,
conditional upon perceived levels of punitive work climate, error feedback, or
preventative procedures. RESULTS: Pharmacists disagreeing that procedures were
sufficient and that feedback on errors was adequate were more likely to report
that near-miss errors were rarely reported (odds ratio [OR], 2.5; 95% confidence
interval [CI], 1.7-3.8; OR, 3.5; 95% CI, 2.5-5.1). Those agreeing that mistakes
were held against them were equally likely as those disagreeing to report that
errors were rarely reported (OR, 0.84; 95% CI, 0.61-1.1). CONCLUSIONS: Inadequate
error feedback to staff and insufficient preventative procedures increase the
likelihood that near-miss errors will be underreported. Hospitals seeking to
improve near-miss error reporting should improve error-reporting infrastructures
to enable feedback, which, in turn, would create a more preventative system that
improves patient safety.
PMID- 25119779
TI - Unique immunomodulatory effects of azelastine on dendritic cells in vitro.
AB - Allergic contact dermatitis and atopic dermatitis are among the most common
inflammatory skin diseases in western countries, and antigen-presenting cells
like dendritic cells (DC) are key players in their pathophysiology. Histamine, an
important mediator of allergic reactions, influences DC maturation and cytokine
secretion, which led us to investigate the immunomodulatory potential of the well
known histamine H1 receptor antagonists: azelastine, olopatadine, cetirizine, and
pyrilamine. Unlike other H1 antihistamines, azelastine decreased
lipopolysaccharide-induced tumor necrosis factor alpha and interleukin-12
secretion from murine bone marrow-derived DC. This effect was independent of
histamine receptors H1, H2, or H4 and may be linked to inhibition of the nuclear
factor kappa B pathway. Moreover, only azelastine reduced proliferation of
allogenic T cells in a mixed leukocyte reaction. We then tested topical
application of the H1 antihistamines on mice sensitized against toluene-2,4
diisocyanate, a model of Th2-mediated allergic contact dermatitis. In contrast to
the in vitro results, all investigated substances were efficacious in reducing
allergic ear swelling. Azelastine has unique effects on dendritic cells and T
cell interaction in vitro. However, this did not translate into superior in vivo
efficacy for Th2-mediated allergic dermatitis, possibly due to the effects of the
antihistamines on other cell types involved in skin inflammation. Future research
will have to clarify whether these properties are relevant to in vivo models of
allergic inflammation with a different T cell polarization.
PMID- 25119781
TI - Racial and Ethnic Disparities in Patient Safety.
AB - BACKGROUND: Although there is extensive evidence on disparities in the process
and outcomes of health care, data on racial and ethnic disparities in patient
safety remain inconclusive in the United States. OBJECTIVES: The aims of this
study were to (1) explore differences in reporting race/ethnicity in studies on
disparities in patient safety; (2) assess adjustment for socioeconomic status,
comorbidity, and disease severity; and (3) make recommendations on the inclusion
of race/ethnicity for future studies on adverse events. METHODS: We searched
PubMed database (for articles published from 1991 to May 1, 2013) using a
predetermined criteria for studies on racial and ethnic disparities in patient
safety. Only quantitative studies that used chart review or administrative data
for the detection of adverse events were considered for eligibility. Two
reviewers independently extracted data on inclusion of race/ethnicity in baseline
characteristics and in stratification of outcomes. RESULTS: A total of 174
studies were initially obtained from the search. Of these, 24 met inclusion
criteria and received full-text review. Meta-analysis was not performed because
of the methodological and statistical heterogeneity between studies. Eight
studies included race/ethnicity in baseline characteristics and adjusted for
confounders. Hospital-level variations such teaching status and percentage of
minorities served were infrequently analyzed. CONCLUSIONS: To our knowledge, this
is the first methodological review of racial/ethnic disparities in patient safety
in the United States. The evidence on the existence of disparities in adverse
events was mixed. Poor stratification of outcomes by race/ethnicity and
consideration of geographic and hospital-level variations explain the
inconclusive evidence; variations in the quality of care at hospitals should be
considered in studies using national databases.
PMID- 25119776
TI - Mice Lacking Functional Fas Death Receptors Are Protected from Kainic Acid
Induced Apoptosis in the Hippocampus.
AB - The Fas receptor (FasR)/Fas ligand (FasL) system plays a significant role in the
process of neuronal loss in neurological disorders. Thus, in the present study,
we used a real-time PCR array focused apoptosis (Mouse Apoptosis RT(2) PCR Array)
to study the role of the Fas pathway in the apoptotic process that occurs in a
kainic acid (KA) mice experimental model. In fact, significant changes in the
transcriptional activity of a total of 23 genes were found in the hippocampus of
wild-type C57BL/6 mice after 12 h of KA treatment compared to untreated mice.
Among the up-regulated genes, we found key factors involved in the extrinsic
apoptotic pathway, such as tnf, fas and fasL, and also in caspase genes (caspase
4, caspase-8 and caspase-3). To discern the importance of the FasR/FasL pathway,
mice lacking the functional Fas death receptor (lpr) were also treated with KA.
After 24 h of neurotoxin treatment, lpr mice exhibited a reduced number of
apoptotic positive cells, determined by the terminal deoxynucleotidyl transferase
dUTP nick end labelling (TUNEL) method in different regions of the hippocampus,
when compared to wild-type mice. In addition, treatment of lpr mice with KA did
not produce significant changes in the transcriptional activity of genes related
to apoptosis in the hippocampus, either in the fas and fas ligand genes or in
caspase-4 and caspase-8 and the executioner caspase-3 genes, as occurred in wild
type C57BL/6 mice. Thus, these data provide direct evidence that Fas signalling
plays a key role in the induction of apoptosis in the hippocampus following KA
treatment, making the inhibition of the death receptor pathway a potentially
suitable target for excitotoxicity neuroprotection in neurological conditions
such as epilepsy.
PMID- 25119782
TI - Organizational, Cultural, and Psychological Determinants of Smart Infusion Pump
Work Arounds: A Study of 3 U.S. Health Systems.
AB - OBJECTIVES: We investigated nurse perceptions of smart infusion medication pumps
to provide evidence-based insights on how to help reduce work around and improve
compliance with patient safety policies. Specifically, we investigated the
following 3 research questions: (1) What are nurses' current attitudes about
smart infusion pumps? (2) What do nurses think are the causes of smart infusion
pump work arounds? and (3) To whom do nurses turn for smart infusion pump
training and troubleshooting? METHODS: We surveyed a large number of nurses (N =
818) in 3 U.S.-based health care systems to address the research questions above.
We assessed nurses' opinions about smart infusion pumps, organizational
perceptions, and the reasons for work arounds using a voluntary and anonymous Web
based survey. Using qualitative research methods, we coded open-ended responses
to questions about the reasons for work arounds to organize responses into useful
categories. RESULTS: The nurses reported widespread satisfaction with smart
infusion pumps. However, they reported numerous organizational, cultural, and
psychological causes of smart pump work arounds. Of 1029 open-ended responses to
the question "why do smart pump work arounds occur?" approximately 44% of the
causes were technology related, 47% were organization related, and 9% were
related to individual factors. Finally, an overwhelming majority of nurses
reported seeking solutions to smart pump problems from coworkers and being
trained primarily on the job. DISCUSSION AND CONCLUSIONS: Hospitals may
significantly improve adherence to smart pump safety features by addressing the
nontechnical causes of work arounds and by providing more leadership and
formalized training for resolving smart pump-related problems.
PMID- 25119783
TI - Sociocultural Factors Influencing Incident Reporting Among Physicians and Nurses:
Understanding Frames Underlying Self- and Peer-Reporting Practices.
AB - OBJECTIVES: Voluntary reporting of incidents is a common approach for improving
patient safety. Reporting behaviors may vary because of different frames within
and across professions, where frames are templates that individuals hold and that
guide interpretation of events. Our objectives were to investigate frames of
physicians and nurses who report into a voluntary incident reporting system as
well as to understand enablers and inhibitors of self-reporting and peer
reporting. METHODS: This is a qualitative case study-confidential in-depth
interviews with physicians and nurses in General Internal Medicine in a Canadian
tertiary care hospital. RESULTS: Frames that health care practitioners use in
their reporting practices serve as enablers and inhibitors for self-reporting and
peer reporting. Frames that inhibit reporting are shared by physicians and
nurses, such as the fear of blame frame regarding self-reporting and the
tattletale frame regarding peer reporting. These frames are underpinned by a
focus on the individual, despite the organizational message of reporting for
learning. A learning frame is an enabler to incident reporting. Viewing the
objective of voluntary incident reporting as learning allows practitioners to
depersonalize incident reporting. The focus becomes preventing recurrence and not
the individual reporting or reported on. CONCLUSIONS: Physicians and nurses use
various frames that bound their views of self and peer incident reporting-further
progress should incorporate an understanding of these deep-seated views and
beliefs.
PMID- 25119784
TI - Patient Handoffs: Is Cross Cover or Night Shift Better?
AB - OBJECTIVES: Studies show singular handoffs between health care providers to be
risky. Few describe sequential handoffs or compare handoffs from different
provider types. We investigated the transfer of information across 2 handoffs
using a piloted survey instrument. We compared cross-cover (every fourth night
call) with dedicated night-shift residents. METHODS: Surveys assessing provider
knowledge of hospitalized patients were administered to pediatric residents.
Primary teams were surveyed about their handoff upon completion of daytime
coverage of a patient. Night-shift or cross-covering residents were surveyed
about their handoff of the same patient upon completion of overnight coverage.
Pediatric hospitalists rated the consistency of information between the surveys.
Absolute difference was calculated between the 2 providers' rating of a patient's
(a) complexity and (b) illness severity. Scores were compared across provider
type. RESULTS: Fifty-nine complete handoff pairs were obtained. Fourteen and 45
handoff surveys were completed by a cross-covering and a night-shift provider,
respectively. There was no significant difference in information consistency
between primary and night-shift (median, 4.0; interquartile range [IQR], 3-4)
versus primary and cross-covering providers (median, 4.0; IQR, 3-4). There was no
significant difference in median patient complexity ratings (night shift, 3.0;
IQR, 1-5, versus cross cover, 3.5; IQR, 1-5) or illness severity ratings (night
shift, 2.0; IQR, 1-4, versus cross-cover, 3.0; IQR, 1-6) when comparing provider
types giving a handoff. CONCLUSIONS: We did not find a difference in physicians'
transfer of information during 2 handoffs among providers taking traditional call
or on night shift. Development of tools to measure handoff consistency is needed.
PMID- 25119785
TI - A Step Toward High Reliability: Implementation of a Daily Safety Brief in a
Children's Hospital.
AB - OBJECTIVES: Health care is a high-risk industry. To improve communication about
daily events and begin the journey toward a high reliability organization, the
Riley Hospital for Children at Indiana University Health implemented a daily
safety brief. METHODS: Various departments in our children's hospital were asked
to participate in a daily safety brief, reporting daily events and unexpected
outcomes within their scope of responsibility. Participants were surveyed before
and after implementation of the safety brief about communication and awareness of
events in the hospital. The length of the brief and percentage of departments
reporting unexpected outcomes were measured. RESULTS: The analysis of the
presurvey and the postsurvey showed a statistically significant improvement in
the questions related to the awareness of daily events as well as communication
and relationships between departments. The monthly mean length of time for the
brief was 15 minutes or less. Unexpected outcomes were reported by 50% of the
departments for 8 months. CONCLUSIONS: A daily safety brief can be successfully
implemented in a children's hospital. Communication between departments and
awareness of daily events were improved. Implementation of a daily safety brief
is a step toward becoming a high reliability organization.
PMID- 25119786
TI - Application of Failure Mode Effect Analysis to Improve the Care of Septic
Patients Admitted Through the Emergency Department.
AB - BACKGROUND: Failure mode effect analysis (FMEA) is a proactive multistep tool
used to analyze risks, identify failures before they occur, and prioritize
preventive measures. METHODS: A multidisciplinary team trained on FMEA
methodology analyzed the process of treatment of septic patients and recorded
processes under 3 major phases (recognition of severe sepsis, referral, and
resuscitation). The team identified potential failure modes in each process;
assigned severity, occurrence, and detection scores for each; and calculated the
risk priority numbers (RPNs). Finally, higher-priority failure modes (RPN of
>=300) were analyzed to redesign the care process. RESULTS: We identified 27
processes and 48 failure modes with a mean RPN of 270. Twenty-two high-risk
failures were identified by RPN of 300 or higher. All identified critical
processes were related to phase 1 (recognition of sepsis) and phase 3
(resuscitation). The most critical process seemed to be related to the initial
workup and treatment of septic patients, with 4 potential failure modes and a
total RPN of 1485. CONCLUSIONS: Patient safety and care reliability issues are a
major concern in health care. This study suggests that tools such as FMEA can
enable a detailed analysis of the care process of septic patients by outlining
potential failure modes and guiding improvement efforts.
PMID- 25119787
TI - Improving Insulin Administration Through Redesigning Processes of Care: A
Multidisciplinary Team Approach.
AB - OBJECTIVES: This article describes a quality improvement project using a
multidisciplinary team approach to improve the rate of errors of omission of
preprandial subcutaneous coverage insulin orders. METHODS: A Diabetic Management
Work Group was created to evaluate the system processes that affect success and
failure of timely administration and documentation of preprandial coverage
insulin, commonly referred to as sliding scale coverage. Data before and after
the project were collected to evaluate the effectiveness of a process change
through the bar code medication administration system, in which preprandial
coverage insulin order sets were changed to eliminate errors of omission and
improve documentation. RESULTS: A review of 833 random blood glucose measurements
with corresponding short- or rapid-acting insulin coverage orders was conducted.
A mean error of omission rate of 23.4% was identified with respect to coverage
insulin that was clinically indicated by provider-ordered insulin set but not
administered or documented in the electronic medication record. After process
redesign and implementation, 951 blood glucose measurements with corresponding
insulin coverage orders were randomly reviewed, and a mean of 10.7% of omission
rate for coverage insulin administration was identified. This represented a
decrease in omission of coverage insulin by 54% compared with preprocess
improvement. CONCLUSIONS: Decreased errors of omission as well as improved
administration and documentation of coverage insulin were demonstrated by this
multimodal process change. Scheduled standardized order sets, extensive nursing
staff education, and enhanced efficiency of the existing process led to improved
outcomes.
PMID- 25119788
TI - An overview of measurement activities in the partnership for patients.
AB - The Partnership for Patients, launched in April 2011, is a national quality
improvement initiative from the Department of Health and Human Services that has
set ambitious goals for U.S. providers to improve patient safety and care
transitions. This paper outlines the initiative's measurement strategy,
describing four measurement-related objectives: (1) to track national progress
toward the program goals that U.S. hospitals reduce preventable adverse events by
40% and readmissions by 20%; (2) to support local quality improvement measurement
in participating hospitals by providing the appropriate tools, training, and
programmatic structure; (3) to obtain feedback on hospital and contractor
progress, in close to real time, so the project can be effectively managed; and
(4) to evaluate the program's impact on adverse event and readmission rates.
PMID- 25119789
TI - A multitasking functional group leads to structural diversity using designer C-H
activation reaction cascades.
AB - The C-H activation strategy has become one of the preferred methods to introduce
chemical functionality to a chemically inert carbon atom. Intensive efforts have
been devoted to developing either versatile bond formations (product structural
diversity) or effective directing groups (substrate site selectivity). From the
views of medicinal and synthetic practitioners, the C-H activation approach
remains inadequate due to its limitation to point-to-point derivatization. Direct
assembly of 3D molecular complexity in a single step remains elusive for this
strategy. Towards this goal, a multitasking functional group is required to
accomplish several missions in one pot: site selecitivity, cleavability and redox
versatility. We demonstrate that an oxyacetamide group is such a multifunctional
warhead that enables a series of C-H functionalization cascades and allows direct
access to structurally diverse polycyclic heterocyles in one pot. The progress of
these reaction cascades were fully controlled by oxidants and temperature. The
proliferation of the reaction chain can be extended to a four-step cascade.
PMID- 25119790
TI - Curcumin prevents maleate-induced nephrotoxicity: relation to hemodynamic
alterations, oxidative stress, mitochondrial oxygen consumption and activity of
respiratory complex I.
AB - The potential protective effect of the dietary antioxidant curcumin (120
mg/Kg/day for 6 days) against the renal injury induced by maleate was evaluated.
Tubular proteinuria and oxidative stress were induced by a single injection of
maleate (400 mg/kg) in rats. Maleate-induced renal injury included increase in
renal vascular resistance and in the urinary excretion of total protein, glucose,
sodium, neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl beta-D
glucosaminidase (NAG), upregulation of kidney injury molecule (KIM)-1, decrease
in renal blood flow and claudin-2 expression besides of necrosis and apoptosis of
tubular cells on 24 h. Oxidative stress was determined by measuring the oxidation
of lipids and proteins and diminution in renal Nrf2 levels. Studies were also
conducted in renal epithelial LLC-PK1 cells and in mitochondria isolated from
kidneys of all the experimental groups. Maleate induced cell damage and reactive
oxygen species (ROS) production in LLC-PK1 cells in culture. In addition, maleate
treatment reduced oxygen consumption in ADP-stimulated mitochondria and
diminished respiratory control index when using malate/glutamate as substrate.
The activities of both complex I and aconitase were also diminished. All the
above-described alterations were prevented by curcumin. It is concluded that
curcumin is able to attenuate in vivo maleate-induced nephropathy and in vitro
cell damage. The in vivo protection was associated to the prevention of oxidative
stress and preservation of mitochondrial oxygen consumption and activity of
respiratory complex I, and the in vitro protection was associated to the
prevention of ROS production.
PMID- 25119791
TI - Comparison of ready biodegradation estimation methods for fragrance materials.
AB - Biodegradability is fundamental to the assessment of environmental exposure and
risk from organic chemicals. Predictive models can be used to pursue both
regulatory and chemical design (green chemistry) objectives, which are most
effectively met when models are easy to use and available free of charge. The
objective of this work was to evaluate no-cost estimation programs with respect
to prediction of ready biodegradability. Fragrance materials, which are
structurally diverse and have significant exposure potential, were used for this
purpose. Using a database of 222 fragrance compounds with measured ready
biodegradability, 10 models were compared on the basis of overall accuracy,
sensitivity, specificity, and Matthews correlation coefficient (MCC), a measure
of quality for binary classification. The 10 models were VEGA(c) Non-Interactive
Client, START (Toxtree(c)), Biowin(c)1-6, and two models based on inductive
machine learning. Applicability domain (AD) was also considered. Overall accuracy
was ca. 70% and varied little over all models, but sensitivity, specificity and
MCC showed wider variation. Based on MCC, the best models for fragrance compounds
were Biowin6, VEGA and Biowin3. VEGA performance was slightly better for the <50%
of the compounds it identified as having "high reliability" predictions (AD index
>0.8). However, removing compounds with one and only one quaternary carbon
yielded similar improvement in predictivity for VEGA, START, and Biowin3/6, with
a smaller penalty in reduced coverage. Of the nine compounds for which the eight
models (VEGA, START, Biowin1-6) all disagreed with the measured value, measured
analog data were available for seven, and all supported the predicted value.
VEGA, Biowin3 and Biowin6 are judged suitable for ready biodegradability
screening of fragrance compounds.
PMID- 25119792
TI - Strain superlattices and macroscale suspension of graphene induced by corrugated
substrates.
AB - We investigate the organized formation of strain, ripples, and suspended features
in macroscopic graphene sheets transferred onto corrugated substrates made of an
ordered array of silica pillars with variable geometries. Depending on the pitch
and sharpness of the corrugated array, graphene can conformally coat the surface,
partially collapse, or lie fully suspended between pillars in a fakir-like
fashion over tens of micrometers. With increasing pillar density, ripples in
collapsed films display a transition from random oriented pleats emerging from
pillars to organized domains of parallel ripples linking pillars, eventually
leading to suspended tent-like features. Spatially resolved Raman spectroscopy,
atomic force microscopy, and electronic microscopy reveal uniaxial strain domains
in the transferred graphene, which are induced and controlled by the geometry. We
propose a simple theoretical model to explain the structural transition between
fully suspended and collapsed graphene. For the arrays of high density pillars,
graphene membranes stay suspended over macroscopic distances with minimal
interaction with the pillars' apexes. It offers a platform to tailor stress in
graphene layers and opens perspectives for electron transport and nanomechanical
applications.
PMID- 25119794
TI - Evolution of quality of life in patients with Korsakoff's syndrome in a long-term
care facility.
AB - BACKGROUND: Korsakoff's syndrome (KS) is a neuropsychiatric disorder
characterized by severe amnesia. Quality of life (QoL) is becoming an
increasingly used outcome measure in clinical practice but little is known about
QoL in KS and how it may change over time. The purpose of this study was
therefore to assess the QoL in patients with KS at baseline and with a 20-month
follow-up. METHODS: The current study is a longitudinal study on the QoL in
patients with KS living in two long-term care facilities for KS patients in the
Netherlands. QoL was scored with the proxy-based QUALIDEM scale with a 20-month
follow-up. RESULTS: Of the 72 KS patients included at baseline, 57 KS patients
had a follow-up QoL score (79.2%). On the subscales "Feeling at home," "Positive
affect," and "Care relationship" of the QUALIDEM, there was a better QoL in the
follow-up, although effects were relatively small. Other subscales indicated a
stable QoL over time. There were inter-relations between changes in subscales.
CONCLUSIONS: The main finding of this study is that patients with KS on average
do show a relatively stable moderate to good QoL despite the severity of the
syndrome. On specific subscales, there is a small increase in QoL over time.
Results do suggest that prolonged stay in a long-term care facility for KS
patients does have a neutral to a positive effect on QoL in KS.
PMID- 25119795
TI - PM2.5 constituents and hospital emergency-room visits in Shanghai, China.
AB - Although ambient PM2.5 has been linked to adverse health effects, the chemical
constituents that cause harm are largely unclear. Few prior studies in a
developing country have reported the health impacts of PM2.5 constituents. In
this study, we examined the short-term association between PM2.5 constituents and
emergency room visits in Shanghai, China. We measured daily concentrations of
PM2.5, organic carbon (OC), elemental carbon (EC), and eight water-soluble ions
between January 1, 2011 and December 31, 2012. We analyzed the data using
overdispersed generalized linear Poisson models. During our study period, the
mean daily average concentration of PM2.5 in Shanghai was 55 MUg/m(3). Major
contributors to PM2.5 mass included OC, EC, sulfate, nitrate, and ammonium. For a
1-day lag, an interquartile range increment in PM2.5 mass (36.47 MUg/m(3))
corresponded to 0.57% [95% confidence interval (CI): 0.13%, 1.01%] increase of
emergency room visits. In all the three models used, we found significant
positive associations of emergency room visits with OC and EC. Our findings
suggest that PM2.5 constituents from the combustion of fossil fuel (e.g., OC and
EC) may have an appreciable influence on the health impact attributable to PM2.5.
PMID- 25119793
TI - Bromelain surface modification increases the diffusion of silica nanoparticles in
the tumor extracellular matrix.
AB - Tumor extracellular matrix (ECM) represents a major obstacle to the diffusion of
therapeutics and drug delivery systems in cancer parenchyma. This biological
barrier limits the efficacy of promising therapeutic approaches including the
delivery of siRNA or agents intended for thermoablation. After extravasation due
to the enhanced penetration and retention effect of tumor vasculature, typical
nanotherapeutics are unable to reach the nonvascularized and anoxic regions deep
within cancer parenchyma. Here, we developed a simple method to provide
mesoporous silica nanoparticles (MSN) with a proteolytic surface. To this extent,
we chose to conjugate MSN to Bromelain (Br-MSN), a crude enzymatic complex,
purified from pineapple stems, that belongs to the peptidase papain family. This
surface modification increased particle uptake in endothelial, macrophage, and
cancer cell lines with minimal impact on cellular viability. Most importantly Br
MSN showed an increased ability to digest and diffuse in tumor ECM in vitro and
in vivo.
PMID- 25119797
TI - [Triazole antifungal agents: practice guidelines of therapeutic drug monitoring
and perspectives in treatment optimization].
AB - Antifungal triazole agents (fluconazole, voriconazole, itraconazole and
posaconazole) are widely used for the management of invasive fungal infections
(IFI). These drugs are indicated both for the prophylaxis and treatment of IFI,
particularly in candidiasis and aspergillosis, major cause of mortality in
immunocompromised patients. Due to a large interindividual pharmacokinetic
variability leading to sub-therapeutic or toxic concentrations and to
concentration-efficacy and/or -toxicity relationships, therapeutic drug
monitoring (TDM) of antifungal triazole is fully justified. This review provides
an overview of literature based data that confirm the usefulness of such TDM and
its level of evidence as well as the practical guidelines for its implementation.
In addition, we discuss the interest of new tools to improve the clinical
management of IFI, such as genotyping tests optimizing initial voriconazole
dosing regimen or the development of a new solid oral tablet of posaconazole
improving its bioavailability and limiting absorption disorders.
PMID- 25119798
TI - [Pharmacogenetics and prediction of side effects of drugs].
AB - Drug response is often variable from one individual to another, which sometimes
makes them difficult to use when the therapeutic range is narrow. This
interindividual variability in response can be explained in part by genetic
factors affecting the metabolism, transport and the mechanism of action of drugs.
Pharmacogenetics studies the genetic mechanisms involved in the response to drugs
in order to optimize drug therapy, both in terms of efficacy and job security.
This article summarizes the most known present clinical applications that
illustrate the benefit of pharmacogenetic tests available to the clinician and
are feasible for routine therapeutic management of patients (prediction of
efficacy and toxicity of drugs), but also to demonstrate the benefit of
pharmacogenetic tests in terms of health economics (reducing the incidence of
hospitalizations for adverse drug events).
PMID- 25119799
TI - [Determination of the plasma global antioxidant capacity: a critical review].
AB - With respect to prevention of cardiovascular diseases and cancers, the healthcare
professionals are more and more interested in the blood determination of
antioxidants (vitamins C and E, carotenoids, glutathione, ubiquinone, antioxidant
enzymes). The major problem of these analysis is their elevated cost. At the
request of the healthcare professionals, the laboratories of clinical biology
suggest the measurement of the plasma global antioxidant capacity (GAC) as a
replacement of the individual determination of all these antioxidants. The
present review shows that such a test presents a large number of gaps, the major
one being that it essentially reflects the plasma concentration of uric acid and
proteins. On basis of nine arguments, we show that the measurement of the plasma
GAC cannot be considered as an in vivo marker of oxidative stress nor lead to the
prescription antioxidant complement.
PMID- 25119800
TI - [Analytical performances of SPAPLUS(r) turbidimeter for the dosage of
immunoglobulins and beta-2 microglobulin in serum].
AB - We evaluated the analytical performances of the SPAPLUS((r)) immunoturbidimeter
assays manufactured by The Binding Site((r)) for the quantification of thirteen
immunological parameters in serum: IgG, IgA, IgM and IgD immunoglobulins, IgG
subclasses (1 to 4), IgA subclasses (1 and 2), beta-2 microglobulin, free light
chains kappa and lambda. The within-day precision (repeatability) and the between
day precision (reproducibility) were obtained for two or three concentration
levels depending of the parameter and were below the recommendations of the
manufacturer, except for the repeatability of IgG1 (at a level of concentration
of 6.7 g/L). An agreement above 90% (with Bland and Altman analysis) was observed
between the results obtained with SPAPLUS((r)) and those obtained with the
nephelometer IMMAGE((r)) 800 or radial immunodiffusion. The evaluation confirmed
the linearity of the assays and the absence of contamination for all the
parameters tested. We also assessed the practicability of the SPAPLUS((r)) in
terms of maintenance, frequency of calibration and cadence tests. The
SPAPLUS((r)) immunoturbidimeter displays good analytical performances for the
immunological parameters evaluated in the present work.
PMID- 25119801
TI - [Evaluation of the quality of clinical practice guidelines published in the
Annales de Biologie Clinique with the help of the EFLM checklist].
AB - Several tools are available to help evaluate the quality of clinical practice
guidelines (CPG). The AGREE instrument (Appraisal of guidelines for research &
evaluation) is the most consensual tool but it has been designed to assess CPG
methodology only. The European federation of laboratory medicine (EFLM) recently
designed a check-list dedicated to laboratory medicine which is supposed to be
comprehensive and which therefore makes it possible to evaluate more thoroughly
the quality of CPG in laboratory medicine. In the present work we test the
comprehensiveness of this check-list on a sample of CPG written in French and
published in Annales de biologie clinique (ABC). Thus we show that some work
remains to be achieved before a truly comprehensive check-list is designed. We
also show that there is some room for improvement for the CPG published in ABC,
for example regarding the fact that some of these CPG do not provide any
information about allowed durations of transport and of storage of biological
samples before analysis, or about standards of minimal analytical performance, or
about the sensitivities or the specificities of the recommended tests.
PMID- 25119796
TI - [Weakening osteopathies, chronic kidney disease, malabsorption, biological
anomalies of calium/phosphorus metabolism: appropriate indications for a reasoned
reimbursment of serum vitamin D measurement].
PMID- 25119802
TI - [Comparative study of parathormone and vitamin D measurements by three automats:
ADVIA Centaur XP(r) (Siemens), ISYS(r) (IDS) and Liaison(r) (Diasorin)].
AB - Vitamin D (Vit.D) and parathormone (PTH) measurements are usually prescribed for
phosphocalcic metabolism assessment and, especially for Vit.D, more and more
frequently for other pathologies. In order to step up to automated techniques for
these analysis in our laboratory, we tested 3 devices: ADVIA Centaur XP((r))
(Siemens), ISYS((r)) (IDS) and Liaison((r)) (Diasorin), which allow to
simultaneously quantify Vit.D and PTH. The aim of this study was to evaluate the
fidelity of these methods as well as study the correlation between them and the
radioimmunological techniques previously used in our laboratory : " ELSA PTH "
(Iba Cisbio International) and " 25-OH D " (IDS). The comparison of PTH analysis
was performed on a population of chronic renal failure patients undergoing
haemodialysis. According to our study, the 3 devices show acceptable analytical
performances; anyway the measurements realized on the ISYS analyzer are the ones
showing the best results in terms of fidelity, and the closest results to those
obtained with the RIA reference techniques.
PMID- 25119803
TI - Relationships between pharmacokinetic parameters of carbamazepine and therapeutic
response in patients with bipolar disease.
AB - This study aimed to assess the relationship between plasma levels of
carbamazepine and its active metabolite 10,11-epoxide-carbamazepine, and the
therapeutic response in patients with bipolar disease. Thirteen patients were
kept on a fixed individual dose of carbamazepine for 19 weeks under psychiatric
care. Steady-state plasma concentrations of carbamazepine and its metabolite
10,11-epoxide-carbamazepine were measured at weeks 4, 12, and 20 by HPLC essay.
Simultaneously, the psychopathologic state was assessed using the Brief
Psychiatric rating scale (BPRS). Upon correlational analysis, mean BPRS scores
did not correlate with the plasma levels of carbamazepine, whereas both mean
plasma levels of 10, 11-epoxide-carbamazepine concentrations and 10,11-epoxide
carbamazepine to plasma carbamazepine ratio were closely correlated with mean
values of BPRS scores (r = 0.80, p =10(-4), r= -0.89, p =10(-3) respectively).
Optimum therapeutic response was observed among patients who had a plasma
metabolite level of 1.4 MUg/mL and a plasma carbamazepine concentrations of 7
MUg/mL simultaneously. These results suggest that both plasma carbamazepine and
10,11-epoxide-carbamazepine levels must be fixed to achieve optimum therapeutic
response. In order to reach these conditions, inhibitor drugs (such as valproic
acid) or inductor drugs (such as phenobarbital) of epoxyde-hydrolase might be
coadministered with the carbamazepine in order to adapt the plasma level of 10,11
epoxide-carbamazepine.
PMID- 25119804
TI - [EEQ in clinical embryology: a starting program].
AB - Every laboratory including those working in assisted reproductive technologies
have to be accredited EN ISO 15189 before 2020. This standardisation includes an
external quality evaluation (EQE). In order to work out an EQE tool, we used
images extracted from our own database developed during daily practice. We
achieved an easily online tool called: "EEQ en embryologie clinique", developed
on Biologie prospective web site with ART French biologists Association (Blefco)
expertise in evaluation of early human embryonic stages. In 2013, 38 ART
laboratories participate to the first program with more than 90% of appropriates
results. The present article aims at describing this tool and discussing its
limits.
PMID- 25119805
TI - [Pathophysiological characterization of metabolic syndrome in overweight, obese
and type 2 diabetic Algerian subjects: interest of adipokines as dysmetabolic
biomarkers].
AB - The body fat accretion (BFA) is correlated to energy homeostasis and/or
hemodynamic dysfunction, being mediated by insulin resistance, dyslipidemia and
recently by adipokines. OBJECTIVES: In this study, we investigated the
associations between metabolic syndrome markers and the secretion disturbs of
leptin, adiponectin and resistin during overweight (OW), obesity (OB) and type 2
diabetes de type 2 (T2DM) stages. PATIENTS AND METHODS: The study was undertaken
on 240 subjects who were divided in 3 groups: overweight, obese and diabetic
groups, according to age, sex and the BMI value. The metabolic syndrome was
investigated according to the NCEP/ATPIII criteria. Insulin resistance was
assessed by HOMA model. Metabolic parameters were determined on Cobas(r).
Adipokines (leptin, adiponectin, resistin) by enzyme linked immunosorbent assay
on human ELISA reader - Biotek ELX 800. RESULTS: The adipokines secretion is
influenced by the adipose tissue accretion and insulin resistance state. The BFA
in OB and OW subjects is positively correlated to the increase of serum leptin,
whereas the serum adiponectin is reduced. The serum adipokines profile is
modulated differently between men and women, particularly for leptin. Resistin
secretion follows the evolution of leptinemia. CONCLUSION: It appears that
adipokines as major dysmetabolic biomarkers, and can be considered as relevant
biological tools in the diagnosis of cardiovascular and T2DM predictive risk in
overweight and obese subjects.
PMID- 25119806
TI - [Cytogenetics study of chromosomal instability in Fanconi anemia in Tunisia].
AB - Cells of Fanconi anemia (FA) is characterized by cellular and chromosomal
hypersensitivity to DNA cross-linking agents. We tested mitomycin C at 25 ng/mL,
40 ng/mL and diepoxybutane 0.1 MUg/mL in order to select a reference technique in
the diagnosis of AF. We also studied the mitotic segregation of sex chromosomes.
Our study focused on 73 patients with aplastic anemia suspecting AF and also 17
healthy controls. Thus, the MMC 25 ng/mL with a sensitivity to detect AF cells.
DEB, by contrast, showed better specificity. FISH study shows the presence of
instability in the AF mitotic cells. The association for routine diagnosis of MMC
25 ng/mL and DEB 0.1 mcg/mL, and the search for a mitotic instability by FISH is
the best way of cytogenetic diagnosis of AF.
PMID- 25119807
TI - [Another case of the rare complications of chronic lymphocytic leukemia:
angioedema].
AB - Angioedema is a rare but may be serious (laryngeal edema). This is a recurrent
edema, subcutaneous and/or submucosal, whose cause is a hereditary or acquired
deficiency in C1 inhibiteur (C1 inhibitor fraction of complement). We present the
case of a 56 years old patient who showed recurrent episodes of swelling of the
face and hands in association with chronic lymphocytic leukemia stage A. The
exploration of the complement pathway has allowed retaining the diagnosis of
acquired angioedema type I. The association of angioedema and lymphoproliferative
syndrome is rare; we present this interesting case to discuss it from the
literature data.
PMID- 25119808
TI - A rare pediatric case of cutaneous gamma/delta T-cell lymphoma.
AB - Cutaneous gamma/delta T-cell lymphoma (CGD-TCL) is a recent entity described in
the newly revised World health organization-European organization for research
and treatment of cancer classification of cutaneous lymphomas. Only a few cases
have been reported, of which two pediatric cases. A 15 years old child with a 6
months history of polyadenopathy, cutaneous lesions, general edema and
deterioration of general condition was hospitalized. Results from laboratory
testing, cutaneous histopathology and immunohistochemistry showed a primary CGD
TCL. Staging was completed by a total body computed tomography. Therapy was
planified with SMILE protocol. It is a highly aggressive tumor resistant to
chemotherapy, immunotherapy, and radiation therapy. The GDTCL is characterized by
a worse prognosis with a median survival of 15 months. Early diagnosis is
essential and aggressive therapy is necessary.
PMID- 25119809
TI - [Gemella haemolysans brain abscess in a child with complex congenital heart
disease].
AB - Gemella haemolysans, a Gram positive cocci which are deemed to be the normal
inhabitant of the mucous membranes of the oropharynx, has been recognized as a
pathogen involved in abscess formation. The aim of this case report is to
demonstrate that it is also involved in brain abscess in children. We report, to
our knowledge, the first pediatric case of Gemella haemolysans brain abscess in
an 11 years old child carrying a complex congenital heart disease (dextrocardia
with single right ventricle) which evolved favorably under antibiotic therapy.
Because of its similarity with Streptococcus viridans groupe, Gemella haemolysans
often remains under-diagnosed in the laboratory. The contribution of
microbiologists in its correct identification is very important.
PMID- 25119810
TI - [Immunoanalytical characteristics of galectin-3].
AB - This paper points out the structural and physiological data of galectin-3, and
emphasizes its role in cardiac fibrosis and heart failure pathophysiology. Then
we summarize the optimal conditions for sampling, assays and we discuss the
interpretation of results.
PMID- 25119811
TI - [Metabolic and inflammatory profiles in polycystic ovary syndrome associated to
weight excess].
AB - Polycystic ovary syndrome (PCOS) and weight excess exhibited metabolic
abnormalities and elevated cardiovascular risk. Our objective was to assess
metabolic and inflammatory profiles in women with PCOS associated to weight
excess; 85 women were enrolled. Four groups were then identified with and without
PCOS and/or weight excess. Hyperlipidemia was significantly more observed in the
two groups with weight excess. In whom insulinresistance and high sensitive C
reactive protein were also elevated. Abnormalities observed when PCOS and weight
excess are associated would mimic these observed in isolated weight excess with
some particularities.
PMID- 25119812
TI - Pharmacological and dietary agents for colorectal cancer chemoprevention: effects
on polyamine metabolism (review).
AB - Chemoprevention is the long-term use of different chemical agents, both synthetic
and natural, to prevent or delay the onset of disease. Since colorectal cancer
has a significant environmental component, it is an ideal disease in which to
evaluate the potential benefits of chemopreventive agents. The polyamines,
spermine, spermidine and putrescine have been involved in almost all the steps of
colorectal tumorigenesis. Consequently, polyamine biosynthesis and catabolism can
be considered as promising targets for cancer chemoprevention. A variety of drug
formulations have been tested for their efficacy in affecting polyamines in a
strategy of colorectal cancer prevention. Different molecules, such as
biosynthesis inhibitors and catabolism inducers, have been proposed alone or in
combination with other drugs proved to diminish the colorectal cancer risk.
Interestingly, also diet can play a role in cancer prevention by affecting
polyamines. Several dietary components, such as probiotics or flavonoids, have
been shown to affect the polyamine metabolic pathway in colorectal neoplastic
tissue. On the other hand, the polyamines ingested with diet might contrast the
above cited effects shown by both drugs and nutritional factors. It is,
therefore, fundamental to acquire more data also on these aspects in view of an
innovative approach to colorectal oncology. This review summarizes data on the
role of polyamine metabolism in neoplastic transformation of colorectal mucosa
and as possible target for colorectal cancer chemoprevention. Attention will be
focused on the influence of drugs and nutritional factors on polyamine
metabolism, as well as the role played by dietary polyamines.
PMID- 25119813
TI - Dinuclear zinc(II) complexes with hydrogen bond donors as structural and
functional phosphatase models.
AB - It is becoming increasingly apparent that the secondary coordination sphere can
have a crucial role in determining the functional properties of biomimetic metal
complexes. We have therefore designed and prepared a variety of ligands as
metallo-hydrolase mimics, where hydrogen bonding in the second coordination
sphere is able to influence the structure of the primary coordination sphere and
the substrate binding. The assessment of a structure-function relationship is
based on derivates of 2,6-bis{[bis(pyridin-2-ylmethyl)amino]methyl}-4
methylphenol (HBPMP = HL(1)) and 2-{[bis(pyridin-2-ylmethyl)amino]methyl}-6-{[(2
hydroxybenzyl)(pyridin-2-ylmethyl)amino]methyl}-4-methylphenol (H2BPBPMP =
H2L(5)), well-known phenolate-based ligands for metallo-hydrolase mimics. The
model systems provide similar primary coordination spheres but site-specific
modifications in the secondary coordination sphere. Pivaloylamide and amine
moieties were chosen to mimic the secondary coordination sphere of the
phosphatase models, and the four new ligands H3L(2), H3L(3), HL(4), and H4L(6)
vary in the type and geometric position of the H-bond donors and acceptors,
responsible for the positioning of the substrate and release of the product
molecules. Five dinuclear Zn(II) complexes were prepared and structurally
characterized in the solid, and four also in solution. The investigation of the
phosphatase activity of four model complexes illustrates the impact of the H
bonding network: the Michaelis-Menten constants (catalyst-substrate binding) for
all complexes that support hydrogen bonding are smaller than for the reference
complex, and this generally leads to higher catalytic efficiency and higher
turnover numbers.
PMID- 25119816
TI - Orientational and vibrational relaxation dynamics of perylene in the cyclohexane
ethanol binary solvent system.
AB - The rotational dynamics and vibrational population relaxation of the nonpolar
probe molecule perylene have been studied in a series of ethanol-cyclohexane
binary solvent mixtures, with the goal of relating solvent system composition to
local organization. Steady-state spectroscopic data show that there is a
discontinuous dependence of the spectroscopic origin on binary solvent system
composition for perylene. Both rotational diffusion and vibrational population
relaxation time constants show a clear discontinuity between 5% and 7.5% (v/v)
ethanol in cyclohexane, suggesting a discontinuous change on molecular scale
rearrangement in the chromophore local environment. We interpret these results in
the context of the chromophore residing in an environment that is not homogeneous
on the molecular scale and changes in its average conformation with binary
solvent system composition.
PMID- 25119814
TI - Increasing and decreasing the ultrastability of bacterial chemotaxis core
signaling complexes by modifying protein-protein contacts.
AB - The chemosensory signaling array of bacterial chemotaxis is composed of
functional core units containing two receptor trimers of dimers, a homodimeric
CheA kinase, and two CheW adaptor proteins. In vitro reconstitutions generate
individual, functional core units and larger functional assemblies, including
dimers, hexagons, and hexagonal arrays. Such reconstituted complexes have been
shown to have both quasi-stable and ultrastable populations that decay with
lifetimes of 1-2 days and ~3 weeks at 22 degrees C, respectively, where decay
results primarily from proteolysis of the bound kinase [Erbse, A. H., and Falke,
J. J. (2009) Biochemistry 48, 6975-6987; Slivka, P. F., and Falke, J. J. (2012)
Biochemistry 51, 10218-10228]. In this work, we show that the ultrastable
population can be destabilized to the quasi-stable level via the introduction of
a bulky tryptophan residue at either one of two essential protein-protein
interfaces within the core unit: the receptor-kinase contact or kinase-adaptor
interface 1. Moreover, we demonstrate that the quasi-stable population can be
made ultrastable via the introduction of a disulfide bond that covalently
stabilizes the latter interface. The resulting disulfide at least doubles the
functional lifetime of the ultrastable population, to >=5.9 weeks at 22 degrees
C, by protecting the kinase from endogenous and exogenous proteases. Together,
these results indicate that the ultrastability of reconstituted core complexes
requires well-formed contacts among the receptor, kinase, and adaptor proteins,
whereas quasi-stability arises from less perfect contacts that allow slow
proteolysis of the bound kinase. Furthermore, the results reveal that
ultrastability, and perhaps the size or order of chemosensory complexes and
arrays, can be increased by an engineered disulfide bond that covalently cross
links a key interface. Overall, it appears that native ultrastability has evolved
to provide an optimal rather than maximal level of kinetic durability, suggesting
that altered selective pressure could either increase or decrease the functional
lifetime of core complexes.
PMID- 25119815
TI - 14,15-Epoxyeicosa-5,8,11-trienoic Acid (14,15-EET) surrogates: carboxylate
modifications.
AB - The cytochrome P450 eicosanoid 14,15-epoxyeicosa-5,8,11-trienoic acid (14,15-EET)
is a powerful endogenous autacoid that has been ascribed an impressive array of
physiologic functions including regulation of blood pressure. Because 14,15-EET
is chemically and metabolically labile, structurally related surrogates
containing epoxide bioisosteres were introduced and have become useful in vitro
pharmacologic tools but are not suitable for in vivo applications. A new
generation of EET mimics incorporating modifications to the carboxylate were
prepared and evaluated for vasorelaxation and inhibition of soluble epoxide
hydrolase (sEH). Tetrazole 19 (ED50 0.18 MUM) and oxadiazole-5-thione 25 (ED50
0.36 MUM) were 12- and 6-fold more potent, respectively, than 14,15-EET as
vasorelaxants; on the other hand, their ability to block sEH differed
substantially, i.e., 11 vs >500 nM. These data will expedite the development of
potent and specific in vivo drug candidates.
PMID- 25119817
TI - Airflow limitation following cardiopulmonary exercise testing and heavy-intensity
intermittent exercise in children with cystic fibrosis.
AB - The clinical importance of exercise testing and training in the healthcare
management of young patients with cystic fibrosis (CF) is growing. The aim of the
present study was to determine the incidence of airflow limitation following
cardiopulmonary exercise testing (CPET) and heavy-intensity intermittent exercise
(HIIE) in young patients with CF. Nineteen young patients with CF and respective
paired-matched controls performed CPET and HIIE on separate days. Forced
expiratory volume in one second (FEV1) was measured pre- and post each exercise
modality. A fall in FEV1 of 10 % or greater was used to define airflow
limitation. The incidence of airflow limitation was significantly greater in the
CF group than in the controls following CPET (32 vs. 5 %; p = 0.03); however, no
significant difference in the incidence of airflow limitation was shown following
HIIE between the CF group and controls (11 vs. 16 %; p = 0.64). CONCLUSION: Our
data show that the incidence of airflow limitation following CPET in young
patients with CF is high. Therefore, clinicians may wish to identify whether
young CF patients experience airflow limitation following strenuous exercise,
such as CPET, before it is performed. However, HIIE carries a low risk for
airflow limitation and may be prescribed as a safe, yet effective exercise
modality for young patients with CF.
PMID- 25119818
TI - The impact of preterm birth on participation in childhood occupation.
AB - Outcome studies of premature babies have focused their assessments predominately
on neurodevelopmental impairments without relating these deficits to the impact
they have on a child's everyday life. This study aims to determine whether very
'preterm birth alone' impacts on a child's ability to participate in and carry
out childhood activities. Forty-four former premature infants between 6 months
and 5 years 6 months, born in Galway University Hospital, Ireland, without
physical or intellectual disability, were compared with 51 age-matched term-born
infants. Study infants had an average gestation of 29 weeks and birth weight of
1,145 g. Functional skills were assessed using the Adaptive Behavior Assessment
Scale-II and the Assessment of Preschool Children's Participation. Premature
infants had significantly lower mean scores in overall adaptive behaviour
compared to term infants, regardless of whether chronological (difference = 13.6,
95% (CI) = [8.2, 19.1]) or corrected (difference = 6.6, 95% CI = [1.4, 11.8]) age
was used. Premature infants had lower mean scores in conceptual, social and
practical skills, but no difference was found between the groups in intensity or
diversity of participation. CONCLUSION: Premature infants had significantly lower
scores in adaptive behaviour than term infants. This measurable effect of preterm
birth on 'childhood occupations' merits further investigation.
PMID- 25119819
TI - First report of the symbiotic bacterium Xenorhabdus indica associated with the
entomopathogenic nematode Steinernema yirgalemense.
AB - The entomopathogenic nematode Steinernema yirgalemense is considered a promising
agent in the biocontrol of insects. However, little is known about the bacteria
living in symbiosis with the nematode. In this study, we have identified the only
available bacterial strain (157-C) isolated from S. yirgalemense, as a member of
the species Xenorhabdus indica. Identification was based on 16S rDNA, recA, dnaN,
gltX, gyrB and infB gene sequence analyses. The relatedness of strain 157-C to
the type strain of X. indica (DSM 17 382) was confirmed with DNA-DNA
hybridization. The phenotypic characteristics of strain 157-C are similar to
those described for the type strain of X. indica. This is the first report
associating X. indica with S. yirgalemense.
PMID- 25119820
TI - Is sperm hyaluronic acid binding ability predictive for clinical success of
intracytoplasmic sperm injection: PICSI vs. ICSI?
AB - Although intracytoplasmic sperm injection (ICSI) is now a widely-used technique,
it is still of interest to improve our knowledge as to which is the best
spermatozoon to be selected for ICSI. Infertile men have increased risks of
producing aneuploid spermatozoa. Using hyaluronic acid (HA)-binding sperm
selection may reduce the genetic risks such as chromosomal aberrations of
offspring. In the present study we examined the clinical success of ICSI with HA
selected sperm ('physiologic' ICSI, PICSI) compared to conventional ICSI, as well
as the necessity to differentiate patients according to the initial HA-binding
assay result (HBA score) and whether the sperm concentration or HBA score can
provide additional information. We observed a significantly higher fertilization
rate (FR) of the PICSI group with >60% HBA, implantation rate (IR) of the PICSI
group with <= 60% HBA, and clinical pregnancy rate (CPR) in every PICSI group
compared to the ICSI groups (p < 0.01). We also observed a significantly higher
life birth rate (LBR) in the PICSI group with <= 60% HBA compared to ICSI
patients with <= 60% HBA (p < 0.001). The pregnancy loss rate (PLR) was
significantly lower in PICSI patients compared to the ICSI group (p < 0.0001).
The FR, IR, CPR, and LBR of the PICSI group with <50% HBA were significantly
higher and the PLR was lower than in the ICSI group with <50% HBA (p < 0.01). A
statistically significant correlation was found between the sperm concentration
and the HA-binding capacity (r = 0.62, p < 0.001). We found a closer relationship
between HBA score and FR (r = 0.53, NS) than between sperm concentration and FR
(r = 0.14, NS). HBA could be considered for sperm selection prior to ICSI because
of its success and apparent ability to reduce genetic complications. However,
this must be extended to a larger study.
PMID- 25119823
TI - Geoscience themed issue: editorial.
PMID- 25119821
TI - An easy and efficient method for native and immunoreactive Echinococcus
granulosus antigen 5 enrichment from hydatid cyst fluid.
AB - BACKGROUND: Currently, the serodiagnosis of cystic echinococcosis relies mostly
on crude Echinococcus granulosus hydatid cyst fluid as the antigen. Consequently,
available immunodiagnostic tests lack standardization of the target antigen and,
in turn, this is reflected on poor sensitivity and specificity of the serological
diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: Here, a chromatographic method
enabling the generation of highly enriched Antigen 5 (Ag5) is described. The
procedure is very easy, efficient and reproducible, since different hydatid cyst
fluid (HCF) sources produced very similar chromatograms, notwithstanding the
clearly evident and extreme heterogeneity of the starting material. In addition,
the performance of the antigen preparation in immunological assays was
preliminarily assessed by western immunoblotting and ELISA on a limited panel of
cystic echinococcosis patients and healthy controls. Following western
immunoblotting and ELISA experiments, a high reactivity of patient sera was seen,
with unambiguous and highly specific results. CONCLUSIONS/SIGNIFICANCE: The
methods and results reported open interesting perspectives for the development of
sensitive diagnostic tools to enable the timely and unambiguous detection of
cystic echinococcosis antibodies in patient sera.
PMID- 25119825
TI - Nut crop yield records show that budbreak-based chilling requirements may not
reflect yield decline chill thresholds.
AB - Warming winters due to climate change may critically affect temperate tree
species. Insufficiently cold winters are thought to result in fewer viable flower
buds and the subsequent development of fewer fruits or nuts, decreasing the yield
of an orchard or fecundity of a species. The best existing approximation for a
threshold of sufficient cold accumulation, the "chilling requirement" of a
species or variety, has been quantified by manipulating or modeling the
conditions that result in dormant bud breaking. However, the physiological
processes that affect budbreak are not the same as those that determine yield.
This study sought to test whether budbreak-based chilling thresholds can
reasonably approximate the thresholds that affect yield, particularly regarding
the potential impacts of climate change on temperate tree crop yields. County
wide yield records for almond (Prunus dulcis), pistachio (Pistacia vera), and
walnut (Juglans regia) in the Central Valley of California were compared with 50
years of weather records. Bayesian nonparametric function estimation was used to
model yield potentials at varying amounts of chill accumulation. In almonds,
average yields occurred when chill accumulation was close to the budbreak-based
chilling requirement. However, in the other two crops, pistachios and walnuts,
the best previous estimate of the budbreak-based chilling requirements was 19-32
% higher than the chilling accumulations associated with average or above average
yields. This research indicates that physiological processes beyond requirements
for budbreak should be considered when estimating chill accumulation thresholds
of yield decline and potential impacts of climate change.
PMID- 25119822
TI - The association of PTPN22 R620W polymorphism is stronger with late-onset AChR
myasthenia gravis in Turkey.
AB - A functional single nucleotide polymorphism (SNP) of the PTPN22 gene encoding a
protein tyrosine phosphatase has been associated with autoimmune disorders
including myasthenia gravis (MG). As the PTPN22 R620W polymorphism has a wide
variation of allele frequencies among different populations, this polymorphism
was investigated in MG in Turkey. An emphasis is put on MG subgroups according to
autoantibody (Abs) production and presence of thymoma. DNA samples from 416
patients with clinically diagnosed generalized MG (231 with Abs to acetylcholine
receptor, AChR-MG), 53 with Abs to muscle-specific kinase (MuSK-MG), 55 patients
with no detectable Abs (SN-MG), 77 patients with thymoma (TAMG) and 293 healthy
controls (HC) were genotyped for the SNP (PTPN22 R620W, C1858T, rs2476601). The
PTPN22 T allele was increased in AChR-MG patients (odds ratio [OR]: 2.5, 95%CI:
1.2-5.1). The association was stronger in late disease-onset AChR (LOMG, OR: 3.1,
95%CI: 1.2-8.2). MuSK-MG, SN-MG and TAMG groups did not carry the variant allele
more frequently than the HC. In contrast to findings in other autoimmune
diseases, the distribution of the PTPN22 polymorphism in this population provides
a susceptibility marker for AChR-MG. The strongest association is detected in
patients with LOMG.
PMID- 25119826
TI - Sport events and climate for visitors--the case of FIFA World Cup in Qatar 2022.
AB - The effect of weather on sport events is not well studied. It requires special
attention if the event is taking place at a time and place with extreme weather
situations. For the world soccer championship in Qatar (Doha 2022), human
biometeorological analysis has been performed in order to identify the time of
the year that is most suitable in terms of thermal comfort for visitors attending
the event. The analysis is based on thermal indices like Physiologically
Equivalent Temperature (PET). The results show that this kind of event may be not
appropriate for visitors, if it is placed during months with extreme conditions.
For Doha, this is the period from May to September, when conditions during a
large majority of hours of the day cause strong heat stress for the visitors. A
more appropriate time would be the months November to February, when thermally
comfortable conditions are much more frequent. The methods applied here can
quantify the thermal conditions and show limitations and possibilities for
specific events and locations.
PMID- 25119828
TI - The CC chemokine ligand 2 (CCL2) polymorphism -2518A/G is associated with gout in
the Chinese Han male population.
AB - Gout is usually characterized by uric acid-induced recurrent attacks of acute
inflammatory arthritis. CC chemokine ligand 2 (CCL2), a chemokine involved in the
recruitment and migration of monocytes/macrophages, has previously been shown to
be increased in the plasma of gout patients. In this study, we examined whether
the CCL2 -2518A/G (rs1024611) single nucleotide polymorphism (SNP) affects
susceptibility to gout in a Chinese Han male population. Genomic DNA from gout
patients (n = 1,109) and ethnically matched gout-free controls (n = 1,034) was
genotyped for the CCL2 -2518A/G SNP using polymerase chain reaction-restriction
fragment length polymorphism. The Chi-square test was performed to investigate
the association of genotypic and allelic frequencies between cases and controls,
and the -2518G allele was shown to be associated with a significantly increased
risk of gout development [P = 0.007, odds ratio 1.182, 95% confidence interval
1.047-1.335]. The GG genotypic distribution was also significantly different
between cases and controls (adjusted P = 0.021). However, genotypic distributions
and allelic frequencies did not indicate significant associations (P = 0.150 and
P = 0.050, respectively) between tophi and non-tophi patients. Our findings
support a key role for the CCL2 SNP -2518A/G in association with gout
susceptibility in the Chinese Han male population. However, additional studies in
other populations should be carried out to confirm this finding.
PMID- 25119827
TI - An investigation into the relationship between anti-Helicobacter pylori and anti
Saccharomyces cerevisiae antibodies in patients with axial spondyloarthritis and
Crohn disease.
AB - Spondyloarthritis (SpA) is a musculoskeletal inflammatory disease linked with
immune responses to intestinal microbiota, and subclinical intestinal ulcerations
that are closely related to inflammatory bowel diseases. Helicobacter pylori is a
common cause of gastroduodenal ulceration, and anti-Saccharomyces cerevisiae
antibodies (ASCA) are associated with intestinal inflammation in both Crohn
disease (CD) and SpA. We investigated the relationship between H. pylori and
ASCA. Ninety-one patients with axial SpA and forty with CD were included. ASCA
IgG/IgA and anti-H. pylori IgG titers were assessed by ELISA. The proportion of
ASCA+ patients in the positive and negative anti-H. pylori IgG groups with SpA
and CD were compared using Chi-square tests, and correlations were evaluated
using the Spearman's coefficient. Anti-H. pylori IgG titers were significantly
negatively correlated with the ASCA IgG (r = -0.563, p < 0.001) and IgA (r =
0.342, p = 0.019) titers in the axial SpA patients. The same pattern of negative
correlation was also observed in the CD patients. Anti-H. pylori+ serology was
significantly more frequent in axial SpA patients than in those with CD (52.4 vs.
18.4 %, p < 0.001), while ASCA+ serology was significantly more frequent in CD
patients than in SpA patients. A negative correlation between the anti-H. pylori
titers and ASCA was found for axial SpA and CD. Anti-H. pylori+ serology was more
frequent in SpA than in CD, while ASCA positivity was more frequent in CD
patients than in those with SpA. A possible influence of H. pylori on the
development of ASCA needs further investigation.
PMID- 25119829
TI - Frequency of joint involvement in juvenile idiopathic arthritis during a 5-year
follow-up of newly diagnosed patients: implications for MR imaging as outcome
measure.
AB - To assess the sequence and type of active joints in a cohort of newly diagnosed
juvenile idiopathic arthritis (JIA) patients with full access to current
treatment at first visit and during a follow-up period of 5-years, in order to
identify an index joint/group of joints for magnetic resonance imaging in JIA.
Patient charts of all consecutive newly diagnosed JIA patients with a follow-up
duration of at least 5 years were analyzed. Patients were derived from two
tertiary pediatric rheumatology centers. Patient characteristics and data
concerning the presence of joints with arthritis and the use of medication were
recorded. Findings from 95 JIA patients [39 (41 %) oligoarticular and 56 (59 %)
polyarticular] were analyzed. At first visit, distribution of active joints among
patients was as follows: knee (n = 70, 74 %), ankle (n = 55, 58 %), elbow (n =
23, 24 %), wrist (n = 23, 24 %), metacarpophalangeal (MCP) (n = 20, 21 %),
proximal interphalangeal (PIP) (n = 13, 14 %), hip (n = 6, 6 %), shoulder (n = 5,
5 %), and distal interphalangeal (DIP) (n = 4, 4 %) joints. After a follow-up
period of 5 years, the cumulative percentage of patients with specific joint
involvement changed into: knee (n = 88, 93 %), ankle (n = 79, 83 %), elbow (n =
43, 45 %), wrist (n = 38, 40 %), MCP (n = 36, 38 %), PIP (n = 29, 31 %), shoulder
(n = 20, 21 %), hip (n = 17, 19 %), and DIP (n = 9, 10 %) joints. Despite changes
in treatment strategies over the years, the knee remains the most commonly
involved joint at onset and during follow-up in JIA, followed by the ankle,
elbow, and wrist. For the evaluation of outcome with MRI, the knee appears the
most appropriate joint in JIA.
PMID- 25119831
TI - Celiac symptoms in patients with fibromyalgia: a cross-sectional study.
AB - Fibromyalgia is a chronic pain syndrome associated with numerous somatic symptoms
including gastrointestinal manifestations of nonspecific nature. Celiac disease
and nongluten sensitivity frequently evolve in adults with gastrointestinal and
extraintestinal symptoms similar to those found among patients with fibromyalgia.
The objective of the present study was to evaluate the presence of celiac-type
symptoms among patients with fibromyalgia in comparison with healthy subjects and
with those experienced by adult celiac patients and subjects with gluten
sensitivity. A list of typical celiac-type symptoms was developed, comparing the
frequency of presentation of these symptoms between patients with fibromyalgia (N
= 178) and healthy subjects (N = 131), in addition to those of celiac patients
and gluten-sensitive patients reported in the literature. The frequency of
presentation of every celiac-type symptom, excepting anemia, was significantly
higher among patients with fibromyalgia compared to controls (p < 0.0001).
Regarding the existing data in the literature, the prevalence of fatigue,
depression, cognitive symptoms and cutaneous lesions predominated among patients
with fibromyalgia, whereas the prevalence of gastrointestinal symptoms was higher
among patients with fibromyalgia compared to gluten-sensitive patients and was
similar among patients with fibromyalgia and celiac disease patient. The
symptomatological similarity of both pathologies, especially gastrointestinal
symptoms, suggests that at least a subgroup of patients with fibromyalgia could
experience subclinical celiac disease or nonceliac gluten intolerance.
PMID- 25119830
TI - An insight into the gastrointestinal component of fibromyalgia: clinical
manifestations and potential underlying mechanisms.
AB - Fibromyalgia syndrome is characterized by chronic generalized pain accompanied by
a broad symptomatologic spectrum. Besides chronic fatigue, sleep disturbances,
headaches and cognitive dysfunction that are extensively described in the
literature, a considerable proportion of patients with fibromyalgia experience
gastrointestinal symptoms that are commonly overlooked in the studies that are
not specifically dedicated to evaluate these manifestations. Nevertheless,
various attempts were undertaken to explore the gastrointestinal dimension of
fibromyalgia. Several studies have demonstrated an elevated comorbidity of
irritable bowel syndrome (IBS) among patients with fibromyalgia. Other studies
have investigated the frequency of presentation of gastrointestinal symptoms in
fibromyalgia in a nonspecific approach describing several gastrointestinal
complaints frequently reported by these patients such as abdominal pain,
dyspepsia and bowel changes, among others. Several underlying mechanisms that
require further investigation could serve as potential explanatory hypotheses for
the appearance of such manifestations. These include sensitivity to dietary
constituents such as gluten, lactose or FODMAPs or alterations in the brain-gut
axis as a result of small intestinal bacterial overgrowth or subclinical enteric
infections such as giardiasis. The gastrointestinal component of fibromyalgia
constitutes a relevant element of the multidisciplinary pathophysiologic
mechanisms underlying fibromyalgia that need to be unveiled, as this would
contribute to the adequate designation of relevant treatment alternatives
corresponding to these manifestations.
PMID- 25119832
TI - Serum IL-33 level and IL-33 gene polymorphisms in Behcet's disease.
AB - Behcet's disease (BD) is a chronic inflammatory disease. Increased productions of
cytokines including interleukin (IL)-1beta and IL-18 are documented, and IL
1alpha and beta gene polymorphisms are associated with susceptibility to the
disease. IL-33 is a recently discovered member of IL-1 cytokine family. The aim
of the study was to detect serum IL-33 level and IL-33 gene polymorphisms in a
cohort of BD. Unrelated 117 patients with BD and 149 healthy controls (HC) were
enrolled. Serum IL-33 levels were analyzed by enzyme-linked immunosorbent assay
method. DNA samples were harvested using an appropriate commercial DNA isolation
kit. Four single nucleotide polymorphisms of IL-33 gene (rs7044343, rs1157505,
rs11792633 and rs1929992) were genotyped using the appropriate commercial
primer/probe sets on real-time PCR. Serum IL-33 level was not significantly
different in the BD and HC groups (p > 0.05). However, its level was lower in the
active BD patients compared to the inactive ones and HC group (p = 0.044 and p =
0.037, respectively). There was no significant difference in terms of the
genotypic and allelic distributions of rs1157505 and rs1929992 polymorphisms (p >
0.05 for all). However, the TT variants of rs7044343 and rs11792633 polymorphisms
were very rare, and the T allele frequencies of these polymorphisms were lower,
in the BD group compared to the HC group (p < 0.0001 for all). The rs7044343 and
rs11792633 variants of IL-33 gene are associated with the decreased risk of BD in
our cohort. Therefore, it may be concluded that IL-33 acts a protective role on
the pathogenesis of BD.
PMID- 25119833
TI - Neuropsychiatric manifestations and associated autoantibodies in systemic lupus
erythematosus patients from Western India.
AB - Systemic lupus erythematosus with neuropsychiatric involvement (NPSLE) can be
diagnosed clinically, but there is no definite serological biomarker established.
The objectives of this study were to evaluate the neuropsychiatric involvement in
systemic lupus erythematosus (SLE) patients and to detect the autoantibodies
associated with them. Sixty NPSLE patients along with sixty SLE patients without
neuropsychiatric involvement from Maharashtra, India, were included. All patients
were clinically diagnosed using the American College of Rheumatology criteria.
Disease activity was assessed using the systemic lupus erythematosus disease
activity index. Antinuclear antibodies (ANA), anti-dsDNA, anti-neuronal
antibodies were detected by indirect immunofluorescence test. Anti-ribosomal
antibodies (anti-Rib-P) were tested by ELISA. NPSLE was diagnosed in age group
ranging between 10 and 20 years compared with SLE patients without
neuropsychiatric involvement (21-30 years). The most frequent symptoms were
psychosis (75%), followed by seizures (58%), lupus headache (40%), cognitive
dysfunction (36%), mood disorder (30%), cerebrovascular disease (20%), and
anxiety (18%). ANA were present in all. The prevalence of anti-Rib-P was 26.6% in
NPSLE and 16.6% in SLE patients without neuropsychiatric involvement. Anti
neuronal antibodies were found in 56.7% in NPSLE and 43.4% in SLE patients
without neuropsychiatric involvement. Anti-neuronal antibodies were found to be
highest in the patients of psychosis (66.6%) followed by central nerve system
disease (63.63 %) and seizures (56.25%). There was an early onset of
neuropsychiatric involvement. Anti-Rib-P antibodies as well as anti-neuronal
antibodies did not show statistically significant correlation with
neuropsychiatric manifestations in NPSLE patients.
PMID- 25119835
TI - Histological and ultrastructural evidence for zinc sequestration in Solanum
nigrum L.
AB - The accumulation of contaminants in the environment due to anthropogenic
activities is a matter of global concern. Solanum nigrum L. plants, able to
accumulate zinc and hyperaccumulate cadmium, were challenged with 0.025 g Zn L(
1) during 35 days. The localization of Zn in roots, stems and leaves of S. nigrum
plants was evaluated by autometallography (AMG) in order to determine the
specific tissue, cell and subcellular compartments of Zn sequestration. This Zn
concentration resulted in stunted plant growth but no other symptoms of Zn
toxicity. Zinc concentration in the plants was highest in the roots, 666 mg Zn
kg(-1) fresh weight (f.w.), and lower in the stems, 318 mg Zn kg(-1) f.w., and
leaves, 101 mg Zn kg(-1) f.w. Roots of Zn-treated plants showed an underdeveloped
structure but additional layers of proliferating cortical parenchyma cells. AMG
of S. nigrum roots, stems and leaves revealed a generalized Zn distribution
associated with the cell walls in all tissues. In the vasculature (xylem and
phloem), Zn was observed at the plasma membrane-cell wall complex of vascular
parenchyma cells and conducting elements. Conspicuous Zn deposits were detected
in the vacuoles of cortical parenchyma and starch sheath, as well as in the
tonoplast of the mesophyll cells. Our results suggest that Zn flux through the
plant occurs via the xylem and phloem and associated parenchyma until it is
conducted to permanent storage sites, namely, the apoplast and vacuoles of
cortical parenchyma cells of the root, stem and the leaf mesophyll.
PMID- 25119836
TI - A 2-year observational study of patients with relapsing-remitting multiple
sclerosis converting to glatiramer acetate from other disease-modifying
therapies: the COPTIMIZE trial.
AB - Studies suggest that patients with relapsing-remitting multiple sclerosis (RRMS)
who do not benefit from other disease-modifying treatments (DMTs) may benefit
from converting to glatiramer acetate (GA). COPTIMIZE was a 24-month
observational study designed to assess the disease course of patients converting
to GA 20 mg daily from another DMT. Eligible patients had converted to GA and had
received prior DMT for 3-6 months, depending on the reasons for conversion.
Patients were assessed at baseline and at 6, 12, 18, and 24 months. In total, 672
patients from 148 centers worldwide were included in the analysis. Change of
therapy to GA was prompted primarily by lack of efficacy (53.6 %) or intolerable
adverse events (AEs; 44.8 %). Over a 24-month period, 72.7 % of patients were
relapse free. Mean annual relapse rate decreased from 0.86 [95 % confidence
interval (CI) 0.81-0.91] before the change to 0.32 (95 % CI 0.26-0.40; p <
0.0001) at last observation, while the progression of disability was halted, as
the Kurtzke Expanded Disability Status Scale (EDSS) scores remained stable.
Patients improved significantly (p < 0.05) on measures of fatigue, quality of
life, depression, and cognition; mobility scores remained stable. The results
indicate that changing RRMS patients to GA is associated with positive treatment
outcomes.
PMID- 25119834
TI - Emerging roles of pericytes in the regulation of the neurovascular unit in health
and disease.
AB - Pericytes of the central nervous system (CNS) are uniquely positioned within a
multicellular structure termed the neurovascular unit (NVU) to provide crucial
support to blood brain barrier (BBB) formation, maintenance, and stability.
Numerous CNS diseases are associated with some aspect of BBB dysfunction. A
dysfunction can manifest as one or multiple disruptions to any of the following
barriers: physical, metabolic, immunological and transport barrier. A breach in
the BBB can notably result in BBB hyper-permeability, endothelial activation and
enhanced immune-endothelial interaction. How the BBB is regulated within this
integrated unit remains largely unknown, especially as it relates to pericyte
endothelial interaction. We summarize the latest findings on pericyte origin,
possible marker expression, and availability within different organ systems. We
highlight pericyte-endothelial cell interactions, concentrating on extra- and
intra- cellular signaling mechanisms linked to platelet derived growth factor-B,
transforming growth factor -beta, angiopoietins, Notch, and gap junctions. We
discuss the role of pericytes in the NVU under inflammatory insult, focusing on
how pericytes may indirectly affect leukocyte CNS infiltration, the direct role
of pericyte-mediated basement membrane modifications, and immune responses. We
review new findings of pericyte actions in CNS pathologies including Alzheimer's
disease, stroke, multiple sclerosis, diabetic retinopathy, and HIV-1 infection.
The uncovering of the regulatory role of pericytes on the BBB will provide key
insight into how barrier integrity can be re-established during
neuroinflammation.
PMID- 25119837
TI - Cerebrospinal-fluid orexin levels and daytime somnolence in frontotemporal
dementia.
AB - Daytime somnolence and sleep-wake cycle disturbances are commonly encountered
symptoms in Frontotemporal Dementia (FTD). Orexin-A (Hypocretin-1) is a
hypothalamic neuropeptide regulating the sleep-wake rhythm. We investigated the
cerebrospinal-fluid (CSF) orexin levels in a population of FTD patients and
evaluated whether there is a relationship between daytime somnolence and CSF
orexin concentrations. CSF orexin levels were measured in a sample of FTD
patients (n = 11) compared to a population of non-demented controls (n = 13)
similar for age and sex. Moreover, CSF orexin concentrations were correlated with
daytime somnolence investigated by means of the Epworth Sleepiness Scale (ESS) in
both FTD patients and controls. FTD patients showed CSF orexin concentrations
(164.3 +/- 66.45 vs 170.81 +/- 42.73 pg/mL) and ESS scores (7.45 +/- 4.36 vs 3.84
+/- 1.82) not different from controls. However, three FTD patients showed
pathological daytime sleepiness (ESS > 10) coupled with the lowest CSF orexin
levels. In addition, we found a significant negative correlation between CSF
orexin levels and ESS scores in the FTD population (R = -0.91; p < 0.0001), which
was not evident in the control group (R = 0.16; p > 0.05). This is the first
study investigating CSF orexin concentrations in FTD. We did not find differences
in CSF orexin concentrations between FTD patients and controls. However, a
significant negative correlation between daytime somnolence and CSF orexin levels
was evident in FTD patients. Moreover, we have found that pathological daytime
somnolence was evident in those FTD patients with the lowest CSF orexin levels.
Based on these findings, we argued that lower orexin levels may be permissive for
increased daytime somnolence in FTD.
PMID- 25119838
TI - Dopamine transporter availability in motor subtypes of de novo drug-naive
Parkinson's disease.
AB - Tremor dominant (TD) and akinetic-rigid type (ART) are two motor subtypes of
Parkinson's disease associated with different disease progression and
neurochemical/neuropathological features. The role of presynaptic nigrostriatal
dopaminergic damage is still controversial, poorly explored, and only assessed in
medicated patients. In this study, we investigated with FP-CIT SPECT the striatal
dopamine transporter (DAT) availability in drug-naive PD patients with ART and TD
phenotypes. Fifty-one de novo, drug-naive patients with PD underwent FP-CIT SPECT
studies. Patients were evaluated with Unified Parkinson's Disease Rating Scale
(UPDRS) part III and Hoehn and Yahr scale (H&Y) and divided into ART (24/51) and
TD (27/51) according to UPDRS part III. ART and TD patients were not different
with regard to age, gender, and disease duration. However, compared to TD, ART
patients presented higher UPDRS part III (p = 0.01) and H&Y (p = 0.02) and lower
DAT availability in affected and unaffected putamen (p = 0.008 and p = 0.007,
respectively), whereas no differences were found in caudate. Moreover, in the
whole group of patients, rigidity and bradykinesia, but not tremor scores of
UPDRS part III were significantly related to FP-CIT binding in the putamen. These
results suggest that in newly diagnosed drug-naive PD patients DAT availability
might be different between ART and TD in relation to different disease severity.
PMID- 25119839
TI - Detailing intra-lesional venous lumen shrinking in multiple sclerosis
investigated by sFLAIR MRI at 7-T.
AB - Intra-lesional venous lumen shrinking detectable by MRI was suggested as an in
vivo marker of inflammation in multiple sclerosis (MS). In our study mean
diameters of pre-, post- and intra-lesional venous sections were determined in 49
patients with MS or clinically isolated syndrome (CIS) using a pixel-wise
analysis on susceptibility-weighted fluid-attenuated inversion recovery (sFLAIR)
images and T2*-weighted (T2*w) imaging at 7 Tesla (T). We observed post-to-intra
lesional venous lumen shrinking on T2*w images (p = 0.036) in an analysis of 338
venous sections. Pre-to-intra-lesional venous lumen reduction was only detectable
in less than 50% of lesions and failed statistical significance when analysing
T2*w (p = 0.325) and sFLAIR images (p = 0.258). In conclusion, thinning of intra
lesional veins in MS is--if detectable at all--probably less severe than
previously reported, and affects only a minority of MS lesions.
PMID- 25119841
TI - Intracranial hemorrhage risk with the new oral anticoagulants: a systematic
review and meta-analysis.
AB - The new oral anticoagulants/non-vitamin K antagonists oral anticoagulants (NOACs)
have recently reached the market and less is known about their safety in
comparison to their efficacy. Therefore, we aimed to evaluate intracranial
hemorrhage (ICH) risk with NOACs, the most feared adverse event of
anticoagulation treatment. This is a systematic review and meta-analysis of phase
III randomized controlled trials (RCTs) comparing NOACs versus any control and
reporting ICH events. Studies were searched through Medline and Cochrane Library
(April 2014). Reviews and reference lists were also screened. Random effects'
meta-analysis was performed to derive pooled estimates expressed as relative risk
(RR) and 95 % CI. Number needed to treat/harm (NNT/NNH) taking into account the
baseline risk was also calculated. Heterogeneity was evaluated with I (2) test.
18 RCTs evaluating 148,149 patients were included. NOAC significantly reduced ICH
risk compared to vitamin K antagonists (VKA) (RR 0.44; 95 % CI 0.36-0.54; I (2) =
37 %; NNT: 137 during 2 years) and to sequential treatment with low molecular
weight heparin and VKA (RR 0.28; 95 % CI 0.12-0.65; I (2) = 0 %; NNT: 463
patients during 7 months). Compared to placebo, NOACs were associated with an
increased ICH risk (RR 3.31; 95 % CI 1.59-6.90; I (2) = 0 %; NNH: 433 during 1
year). Results were similar for the different NOAC drugs and across the different
clinical conditions. In patients requiring anticoagulation treatment, the risk of
ICH is about half with the NOACs in comparison to standard antithrombotic
treatment. This safer profile found in RCTs should be confirmed in real-world
database studies.
PMID- 25119842
TI - Hippocampal damage and affective disorders after treatment of cerebral aneurysms.
AB - Despite good neurological outcome after the treatment of ruptured or incidental
cerebral aneurysms, many patients complain about mood disturbances such as
anxiety and depression. The present study investigated the nature of these
affective disorders, their trigger factors, and corresponding structural brain
changes. We assessed 63 patients matched by history of previous subarachnoid
hemorrhage (SAH) and treatment modality (clipping vs. coiling) by a test battery
including the Hospital Anxiety and Depression Scale (HADS) and beck depression
inventory-II (BDI-II). MR imaging for the evaluation of structural changes
included H(1)-MR spectroscopy, hippocampal volumetry, and diffusion tensor
imaging (DTI). The applied multimodal imaging revealed no significant differences
between patients with previous SAH and patients with incidental aneurysms; there
were also no substantial differences between patients with and without previous
SAH with respect to depression and anxiety. However, we observed significantly
higher mean HADS scores in patients treated surgically versus patients treated by
coiling (p < 0.01). BDI-II tended to be higher in surgically treated patients,
but this difference appeared statistically insignificant. Surgically treated
patients displayed substantial hippocampal damage in all imaging techniques:
reduction in mean concentrations of N-acetylaspartate (p = 0.04), hippocampal
volume reduction (p = 0.012), and diffusion disorder (p = 0.02). The structural
alterations correlated significantly with the increased HADS scores. In contrast
to endovascular treatment, aneurysm surgery seems to be associated with an
increased incidence of mood disorders corresponding to hippocampal neuronal loss,
independent of preceding SAH.
PMID- 25119844
TI - Reducing central nervous system complications associated with the human
immunodeficiency virus.
PMID- 25119843
TI - The presence of dysautonomia in different subgroups of myasthenia gravis
patients.
AB - To analyze the presence of autonomic dysfunction in different subgroups of
myasthenia gravis (MG) patients. Standard cardiovascular reflex tests according
to Ewing, spectral and time domain analysis of heart rate variability (HRV) at
rest were assessed in 27 patients with thymoma-associated acetylcholine receptor
(AChR)-positive MG, 25 AChR-positive MG patients without thymoma and 23 patients
with muscle-specific tyrosine kinase (MuSK) MG. All patients were compared to the
healthy controls, matched for sex and age. In the group of AChR-positive MG
patients with thymoma, hand grip (p < 0.05), orthostasis (p < 0.05), breathing
test (p < 0.05) and Valsalva maneuver (p < 0.01) were more often pathological
than in the controls. Analysis of the spectral domain of HRV showed increased low
frequency (p < 0.05) and decreased high-frequency component (p < 0.05). Time
domain parameters of HRV and baroreflex sensitivity (BRS) at rest were
significantly reduced (p < 0.01). In the patients with AChR MG without thymoma,
Valsalva maneuver test was more often pathological (p < 0.05) and higher rate of
supraventricular extrasystoles (p < 0.01) was registered than in the healthy
controls. In the patients with MuSK-positive MG, hand grip and Valsalva maneuver
tests were more often pathological than in the controls (p < 0.05). Low-frequency
component of the spectral domain of HRV (p < 0.05) and the frequency of cardiac
arrhythmia were increased. BRS at rest was significantly lower in patients
compared to the controls (p < 0.01). We determined the presence of autonomic
failure in all subgroups of MG patients. Since autonomic dysfunction can lead to
cardiac arrhythmias and even sudden death, it is of major importance to be aware
of this association and to properly diagnose and treat these patients.
PMID- 25119845
TI - Patients' perspectives on the impact of a new COPD diagnosis in the face of
multimorbidity: a qualitative study.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD), a major cause of
morbidity and mortality worldwide, often occurs in the presence of comorbidities,
which may influence experience and management of the disease. No prior research
seems to have gained perspectives of newly diagnosed primary care COPD patients
in the context of multimorbidity. AIMS: This qualitative study aimed to explore
the impact of a new diagnosis of COPD in the context of multimorbidity and also
sought to gain a better understanding of how patients react to the diagnosis and
incorporate it into their lives. METHODS: Participants were identified from a
cohort of primary care patients with multimorbidity recently diagnosed with COPD.
Data was collected via semi-structured interviews from nine male and eight female
participants. Thematic analysis was performed and the data interpreted from a
constructivist perspective. RESULTS: Five core themes regarding COPD were
induced: (i) reaction to diagnosis, (ii) impact on function and health behaviour,
(iii) factors influencing self-management capacity, (iv) healthcare utilisation
and (v) interplay of comorbidities. Most participants had difficulty recognising
the importance of COPD and its long-term implications. For many, the salience of
another chronic condition outweighed COPD. Self-management capacity and
utilisation of healthcare services were challenged by low prioritisation of COPD
among other comorbidities. CONCLUSIONS: This study provides an insight into how
primary care patients feel about being diagnosed with COPD, as well as their
prioritisation of the disease in the context of multimorbidity. It highlights the
need for tailored education and personalised management incorporating patients'
perspectives in primary care.
PMID- 25119846
TI - Simultaneous detection of distinct ubiquitin chain topologies by 19F NMR.
AB - The dynamic interplay between ubiquitin (Ub) chain construction and destruction
is critical for the regulation of many cellular pathways. To understand these
processes, it would be ideal to simultaneously detect different Ub chains as they
are created and destroyed in the cell. This objective cannot be achieved with
existing detection strategies. Here, we report on the use of 19F Nuclear Magnetic
Resonance (NMR) spectroscopy to detect and characterize conformationally distinct
Ub oligomers. By exploiting the environmental sensitivity of the 19F nucleus and
the conformational diversity found among Ub chains of different linkage types, we
can simultaneously resolve the 19F NMR signals for mono-Ub and three distinct di
Ub oligomers (K6, K48, and K63) in heterogeneous mixtures. The utility of this
approach is demonstrated by the ability to interrogate the selectivity of
deubiquitinases with multiple Ub substrates in real time. We also demonstrate
that 19F NMR can be used to discern Ub linkages that are formed by select E3
ligases found in pathogenic bacteria. Collectively, our results assert the
potential of 19F NMR for monitoring Ub signaling in cells to reveal fundamental
insights about the associated cellular pathways.
PMID- 25119848
TI - Characteristics of international staff victims of psychiatric patient assaults:
review of published findings, 2000-2012.
AB - Psychiatric patient assaults on staff are a worldwide occupational hazard that
results in human suffering and dollar cost expense. International research in the
1990s documented the frequent occurrence of these assaults. This present paper
reviewed the published, international literature on staff victim assaults during
the first decade of the new century. The findings indicate assaults on staff
remain a serious worldwide issue as it was in the 1990s, even with new policy
initiatives in place meant to reduce such violence. The findings by continents
and a detailed methodological inquiry are presented.
PMID- 25119849
TI - Comment on: "Insulin glargine in a Brazilian state: should the government
disinvest?".
PMID- 25119847
TI - Suicidality in non-treatment seeking young adults with subsyndromal gambling
disorder.
AB - Gambling Disorder is associated with elevated rates of suicidal thoughts and
acts. However, virtually nothing is known about suicidality in people with
subsyndromal forms of gambling disorder. A total of 174 non-treatment seeking
subjects were recruited for a study of impulsivity and met criteria for a
subsyndromal form of DSM-5 gambling disorder (31.0 % females; mean age = 21.7 +/-
3.61 years). Subjects were categorized as being 'at risk of suicide' or 'no
suicide risk' based on the Mini-International Neuropsychiatric Interview (MINI).
Those with and without suicidality were compared on clinical and cognitive
measures. 32 (18.4 %) met MINI criteria for suicidality. Suicidality was
significantly associated with mood and anxiety disorders, greater rates of
nicotine consumption, and relative impairments in decision-making and cognitive
flexibility. These findings suggest that decision-making impairments may be
implicated in the development of both gambling problems and suicidality. Future
work should address causality, neural correlates, and tailored suicide prevention
strategies for people with, or at risk for, disordered forms of gambling.
PMID- 25119850
TI - Authors' reply to Dr. Malerbi: "Insulin glargine in a Brazilian state: should the
government disinvest?".
PMID- 25119851
TI - The buckling of single-layer MoS2 under uniaxial compression.
AB - Molecular dynamics simulations are performed to investigate the buckling of
single-layer MoS2 under uniaxial compression. The strain rate is found to have an
important effect on the critical buckling strain, where higher strain rate leads
to larger critical strain. The critical strain is almost temperature-independent
for [Formula: see text] K, and it increases with increasing temperature for
[Formula: see text] K owing to the thermal vibration assisted healing mechanism
on the buckling deformation. The length-dependence of the critical strain from
our simulations is in good agreement with the prediction of the Euler buckling
theory.
PMID- 25119852
TI - Responses to ROS inducer agents in zebrafish cell line: differences between
copper and UV-B radiation.
AB - Fish are commonly exposed to environmental pollutants, which in turns could
induce an oxidative stress. So, it is important to understand the effects and the
responses elicited by these toxicants in fish species, being fish cell lines
important tools for this purpose. Thus, the aim of the present study was to
compare the effects of copper and UV-B radiation exposure on zebrafish
hepatocytes (ZFL lineage) in terms of reactive oxygen species (ROS) levels,
sulfhydril groups content and mRNA levels of important genes related to cellular
response to toxic agents. Exposure of ZFL cells to UV-B radiation (23.3 mJ/cm(2))
significantly increased levels of intracellular ROS and mRNA of both superoxide
dismutase isoforms (sod1 and sod2), three glutathione S-transferase isoforms
(gstalpha, gstu and gstpi) and a heat shock protein (hsp70). However, no changes
in nonprotein sulfhydryl groups (NP-SH) content, as well as in the mRNA levels of
genes related to glutathione (GSH) synthesis and recycling, were observed.
Contrary to this, copper exposure (20 mg/L) diminished NP-SH content and
increased the levels of mRNA of genes related to GSH synthesis (gclc and gs).
Moreover, copper exposure increases the mRNA levels of some genes related to
antioxidant defenses (gpx and gstpi), biotransformation reactions (cyp1a1) and
protein repair (hsp70). In conclusion, these results demonstrated that both
toxicants could increase ROS levels in ZFL cell line, but the responses are
different, which could be related to activation of different signaling pathways.
PMID- 25119853
TI - Effects of dietary cholesterol supplementation on growth and cholesterol
metabolism of rainbow trout (Oncorhynchus mykiss) fed diets with cottonseed meal
or rapeseed meal.
AB - This study was conducted to evaluate the effects of cholesterol on growth and
cholesterol metabolism of rainbow trout (Oncorhynchus mykiss) fed diets with
cottonseed meal (CSM) or rapeseed meal (RSM). Four experimental diets were
formulated to contain 550 g kg(-1) CSM or 450 g kg(-1) RSM with or without 9 g
kg(-1) supplemental cholesterol. Growth rate and feed utilization efficiency of
fish fed diets with 450 g kg(-1) RSM were inferior to fish fed diets with 550 g
kg(-1) CSM regardless of cholesterol level. Dietary cholesterol supplementation
increased the growth rate of fish fed diets with RSM, and growth rate and feed
utilization efficiency of fish fed diets with CSM. Similarly, dietary cholesterol
supplementation increased the plasma total cholesterol (TC), high-density
lipoprotein cholesterol, low-density lipoprotein cholesterol, and
triiodothyronine levels, but decreased the plasma triglycerides and cortisol
levels of fish fed diets with RSM or CSM. In addition, supplemental cholesterol
increased the free cholesterol and TC levels in intestinal contents, but
decreased the hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase activity of fish
fed diets with RSM or CSM. These results indicate that 9 g kg(-1) cholesterol
supplementation seems to improve the growth of rainbow trout fed diets with CSM
or RSM, and the growth-promoting action may be related to the alleviation of the
negative effects caused by antinutritional factors and/or make up for the
deficiency of endogenous cholesterol in rainbow trout.
PMID- 25119854
TI - Conditional expression of the type 2 angiotensin II receptor in mesenchymal stem
cells inhibits neointimal formation after arterial injury.
AB - Percutaneous coronary interventions (PCIs) are an effective treatment for
obstructive coronary artery diseases. However, the procedure's success is limited
by remodeling and formation of neointima. In the present study, we engineered rat
mesenchymal stem cells (MSCs) to express type 2 angiotensin II receptor (AT2R)
using a tetracycline-regulated system that can strictly regulate AT2R expression.
We tested the ability of the modified MSCs to reduce neointima formation
following arterial injury. We subjected rats to balloon injury, and reverse
transcriptase polymerase chain reaction (RT-PCR) indicated no significant AT2R
expression in normal rat arteries. Low expression of AT2R was observed at 28 days
after balloon-induced injury. Interestingly, MSCs alone were unable to reduce
neointimal hyperplasia after balloon-induced injury; after transplantation of
modified MSCs, doxycycline treatment significantly upregulated neointimal AT2R
expression and inhibited osteopontin mRNA expression, as well as neointimal
formation. Taken together, these results suggest that transplantation of MSCs
conditionally expressing AT2R could effectively suppress neointimal hyperplasia
following balloon-induced injury. Therefore, MSCs with a doxycycline-controlled
gene induction system may be useful for the management of arterial injury after
PCI.
PMID- 25119856
TI - Biological and analytical stability of a peripheral blood gene expression score
for obstructive coronary artery disease in the PREDICT and COMPASS studies.
AB - A gene expression score (GES) for obstructive coronary artery disease (CAD) has
been validated in two multicenter studies. Receiver-operating characteristics
(ROC) analysis of the GES on an expanded Personalized Risk Evaluation and
Diagnosis in the Coronary Tree (PREDICT) cohort (NCT no. 00500617) with CAD
defined by quantitative coronary angiography (QCA) or clinical reads yielded
similar performance (area under the curve (AUC)=0.70, N=1,502) to the original
validation cohort (AUC=0.70, N=526). Analysis of 138 non-Caucasian and 1,364
Caucasian patients showed very similar performance (AUCs=0.72 vs. 0.70). To
assess analytic stability, stored samples of the original validation cohort
(N=526) was re-tested after 5 years, and the mean score changed from 20.3 to 19.8
after 5 years (N=501, 95 %). To assess patient scores over time, GES was
determined on samples from 173 Coronary Obstruction Detection by Molecular
Personalized Gene Expression (COMPASS) study (NCT no. 01117506) patients at
approximately 1 year post-enrollment. Mean scores increased slightly from 15.9 to
17.3, corresponding to a 2.5 % increase in obstructive CAD likelihood. Changes in
cardiovascular medications did not show a significant change in GES.
PMID- 25119855
TI - Imaging subclinical atherosclerosis: is it ready for prime time? A review.
AB - Imaging subclinical atherosclerosis holds the promise of individualized
cardiovascular (CV) risk assessment. The large arsenal of noninvasive imaging
techniques available today is playing an increasingly important role in the
diagnosis and monitoring of subclinical atherosclerosis. However, there is a
debate about the advisability of clinical screens for subclinical atherosclerosis
and which modality is the most appropriate for monitoring risk and
atherosclerosis progression. This article offers an overview of the traditional
and emerging noninvasive imaging modalities used to detect early atherosclerosis,
surveys population studies addressing the value of subclinical atherosclerosis
detection, and also examines guideline recommendations for their clinical
implementation. The clinical relevance of this manuscript lies in the potential
of current imaging technology to improve CV risk prediction based on traditional
risk factors and the present recommendations for subclinical atherosclerosis
assessment. Noninvasive imaging will also help to identify individuals at high CV
who would benefit from intensive prevention or therapeutic interventions.
PMID- 25119857
TI - A review of the role of electronic health record in genomic research.
AB - Electronic health record (EHR)-driven genomic research is a recent strategy used
to answer research questions using EHR data linked to DNA samples. In models
using EHR, after the subject's DNA is collected, a linkage between the DNA sample
and the EHR data is maintained. This makes the EHR the paramount source of
phenotypic information. The National Human Genome Research Institute sponsored
Electronic Medical Records and Genomics (eMERGE) network began in five sites in
2007 and was expanded to nine sites in 2012. This network has developed the
methods and best practices for utilizing EHR as a tool for genomic research.
Therefore, it is vital to understand the configuration of EHR used to capture
data in clinical practice and feasibility of integration with clinical genetic
test results. We present a detailed review of the role and importance of EHR in
the field of genomic research.
PMID- 25119858
TI - Risk of selected gastrointestinal toxicities in breast cancer patients treated
with regimens containing lapatinib; a pooled analysis of randomized controlled
studies.
AB - We performed a pooled analysis of randomized controlled studies evaluating
selected gastrointestinal adverse events associated with lapatinib use in breast
cancer patients. Eligible studies included randomized Phase II and III trials of
patients with breast cancer on lapatinib; describing events of diarrhea, nausea,
vomiting and stomatitis. Our search strategy yielded 390 potentially relevant
citations on lapatinib from Pubmed/Medline and other databases. After exclusion
of ineligible studies, a total of 19 clinical trials were considered eligible for
the analysis. The relative risk (RR) of all-grade diarrhea, nausea, vomiting and
stomatitis were 3.09 (95% CI: 2.14-4.43; p < 0.00001), 1.24 (95% CI: 1.07- 1.43;
p < 0.005), 1.35 (95% CI: 1.22-1.49; p = 0.0001), 1.96 (95% CI: 1.07-2.67; p =
0.02); respectively. Exploratory subgroup analysis showed no effect of disease
stage on the RR of the relevant adverse events. While, The RR of high-grade
diarrhea, nausea, vomiting and stomatitis were 6.63 (95% CI: 2.94-14.96; p <
0.00001), 1.37 (95% CI: 0.91-2.06; p = 0.13), 1.80 (95% CI: 1.21-2.68; p =
0.004), 2.44 (95% CI: 1.41-4.22 p < 0.001); respectively. Our pooled analysis has
demonstrated that regimens containing lapatinib are associated with a
significantly increased risk of high-grade diarrhea, vomiting and stomatitis in
patients with breast cancer. Clinicians should be aware of these risks and
perform regular clinical monitoring.
PMID- 25119859
TI - Antioxidant defense and hepatoprotection by procyanidins from almond (Prunus
amygdalus) skins.
AB - Procyanidins, polymeric flavan-3-ols, are known to possess antioxidant,
antiatherogenic, and anticarcinogenic properties. In the present study, we
investigated the role of almond (Prunus amygdalus) skin procyanidins (ASP) in
regulating the protein expression of phase II detoxifying and antioxidant enzymes
in HepG2 cells and acetaminophen (APAP)-treated hepatotoxic mice. Treatments of
ASP significantly induced the expression of phase II enzymes including NAD(P)H:
quinoneoxidoreductase 1, catalase, glutathione peroxidase, and superoxide
dismutase in the cells and mice. ASP also potently enhanced the expression of
nuclear factor-E2-related factor 2 (Nrf2) and antioxidant response element (ARE)
reporter gene activity in vitro. APAP-induced hepatotoxic markers including AST
and ALT in mice were inhibited by ASP administration. However, regulation of
upstream kinases by ASP was different between in vitro and in vivo models.
Collectively, ASP could induce the activation of Nrf2/ARE-mediated phase II
detoxifying/antioxidant enzymes but with differential regulation on upstream
kinases between in vitro and in vivo.
PMID- 25119860
TI - Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hormones of energy
balance in a TCDD-sensitive and a TCDD-resistant rat strain.
AB - One of the hallmarks of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD) is a drastically reduced feed intake by an unknown mechanism. To further
elucidate this wasting syndrome, we followed the effects of a single large dose
(100 MUg/kg) of TCDD on the serum levels of several energy balance-influencing
hormones, clinical chemistry variables, and hepatic aryl hydrocarbon receptor
(AHR) expression in two rat strains that differ widely in their TCDD
sensitivities, for up to 10 days. TCDD affected most of the analytes in sensitive
Long-Evans rats, while there were few alterations in the resistant Han/Wistar
strain. However, analyses of feed-restricted unexposed Long-Evans rats indicated
several of the perturbations to be secondary to energy deficiency. Notable
increases in ghrelin and glucagon occurred in TCDD-treated Long-Evans rats alone,
which links these hormones to the wasting syndrome. The newly found energy
balance regulators, insulin-like growth factor 1 and fibroblast growth factor 21
(FGF-21), appeared to function in concert in body weight loss-induced metabolic
state, and FGF-21 was putatively linked to increased lipolysis induced by TCDD.
Finally, we demonstrate a reverse set of changes in the AHR protein and mRNA
response to TCDD and feed restriction, suggesting that AHR might function also as
a physiological regulator, possibly involved in the maintenance of energy
balance.
PMID- 25119863
TI - Silver nanoparticles/ibuprofen-loaded poly(L-lactide) fibrous membrane: anti
infection and anti-adhesion effects.
AB - Infection caused by bacteria is one of the crucial risk factors for tendon
adhesion formation. Silver nanoparticles (AgNP)-loaded physical barriers were
reported to be effective in anti-infection and anti-adhesion. However, high
silver load may lead to kidney and liver damages. This study was designed for
Ibuprofen (IBU)-loaded poly(L-lactide) (PLLA) electrospun fibrous membranes
containing a low dosage of Ag to evaluate its potential in maintaining suitable
anti-infection and good anti-adhesion effects. The in vitro drug release study
showed a sustained release of Ag ions and IBU from the membrane. Inferior
adherence and proliferation of fibroblasts were found on the Ag4%-IBU4%-loaded
PLLA electrospun fibrous membranes in comparison with pure PLLA and 4% Ag-loaded
PLLA membranes. In the antibacterial test, all Ag-loaded PLLA electrospun fibrous
membranes prevented the adhesion of Staphylococcus aureus and Staphylococcus
epidermidis. Taken together, these results demonstrate that Ibuprofen is
effective in enhancing the anti-adhesion and anti-proliferation effects of 4% Ag
loaded PLLA fibrous membrane. The medical potential of infection reduction and
adhesion prevention of Ag4%-IBU4%-loaded PLLA electrospun fibrous membrane
deserves to be further studied.
PMID- 25119861
TI - Mechanistic understanding of toxicity from nanocatalysts.
AB - Nanoparticle-based catalysts, or nanocatalysts, have been applied in various
industrial sectors, including refineries, petrochemical plants, the
pharmaceutical industry, the chemical industry, food processing, and
environmental remediation. As a result, there is an increasing risk of human
exposure to nanocatalysts. This review evaluates the toxicity of popular
nanocatalysts applied in industrial processes in cell and animal models. The
molecular mechanisms associated with such nanotoxicity are emphasized to reveal
common toxicity-inducing pathways from various nanocatalysts and the uniqueness
of each specific nanocatalyst.
PMID- 25119862
TI - Current status of long non-coding RNAs in human cancer with specific focus on
colorectal cancer.
AB - The latest investigations of long non-coding RNAs (lncRNAs) have revealed their
important role in human cancers. LncRNAs are larger than 200 nucleotides in
length and fulfill their cellular purpose without being translated into proteins.
Though the molecular functions of some lncRNAs have been elucidated, there is
still a high number of lncRNAs with unknown or controversial functions. In this
review, we provide an overview of different lncRNAs and their role in human
cancers. In particular, we emphasize their importance in tumorigenesis of
colorectal cancer, the third most common cancer worldwide.
PMID- 25119864
TI - Allogeneic mesenchymal stem cell transplantation for lupus nephritis patients
refractory to conventional therapy.
AB - Allogeneic mesenchymal stem cell transplantation (MSCT) has been shown to be
clinically efficacious in the treatment of various autoimmune diseases. Here, we
analyzed the role of allogeneic MSCT to induce renal remission in patients with
active and refractory lupus nephritis (LN). This is an open-label and single
center clinical trial conducted from 2007 to 2010 in which 81 Chinese patients
with active and refractory LN were enrolled. Allogeneic bone marrow- or umbilical
cord-derived mesenchymal stem cells (MSCs) were administered intravenously at the
dose of 1 million cells per kilogram of bodyweight. All patients were then
monitored over the course of 12 months with periodic follow-up visits to evaluate
renal remission, as well as possible adverse events. The primary outcome was
complete renal remission (CR) and partial remission (PR) at each follow-up, as
well as renal flares. The secondary outcome included renal activity score, total
disease activity score, renal function, and serologic index. During the 12-month
follow-up, the overall rate of survival was 95 % (77/81). Totally, 60.5 % (49/81)
patients achieved renal remission during 12-month visit by MSCT. Eleven of 49
(22.4 %) patients experienced renal flare by the end of 12 months after a
previous remission. Renal activity evaluated by British Isles Lupus Assessment
Group (BILAG) scores significantly declined after MSCT (mean +/- SD, from 4.48 +/
2.60 at baseline to 1.09 +/- 0.83 at 12 months), in parallel with the obvious
amelioration of renal function. Glomerular filtration rate (GFR) improved
significantly 12 months after MSCT (mean +/- SD, from 58.55 +/- 19.16 to 69.51 +/
27.93 mL/min). Total disease activity evaluated by Systemic Lupus Erythematosus
Disease Activity Index (SLEDAI) scores also decreased after treatment (mean +/-
SD, from 13.11 +/- 4.20 at baseline to 5.48 +/- 2.77 at 12 months). Additionally,
the doses of concomitant prednisone and immunosuppressive drugs were tapered. No
transplantation-related adverse event was observed. Allogeneic MSCT resulted in
renal remission for active LN patients within 12-month visit, confirming its use
as a potential therapy for refractory LN.
PMID- 25119866
TI - [Relevance of the current discussion on prioritization for rheumatology].
AB - BACKGROUND: The increase in age-related diseases that can be expected due to
demographic changes, the growing medicalization and the medical technological
progress with new diagnostic and therapeutic methods, will probably lead to
rising health expenditure in the coming years. The resulting financial problems
have so far mostly been countered by an increase in health insurance
contributions, tax subsidies, rationalization and hidden rationing. The
potentials of explicit prioritization processes have so far not been made use of
in Germany compared to some other countries where this is already in common use.
METHODS: Prioritization in the healthcare system is a procedure of mental
clarification and determination of the priority or subordination of certain
indications, patient groups or methods with the result of multilevel ranking.
Human dignity, equality and solidarity are fundamental values on which
prioritization is based. The medical need, the urgency of treatment, the expected
medical benefits, the treatment risk, the cost efficiency and the evidence level
are criteria towards which prioritization is oriented. RESULTS: Prioritization
processes lead to scientifically substantiated care recommendations which support
decisions regarding the medically rational, ethically justifiable and
economically meaningful use of limited resources. In order to gain broad public
acceptance, prioritization guidelines should be developed in a transparent way by
democratically justified committees the composition of which still needs to be
clarified. Fundamental concepts, cornerstones of the current debate and efforts
that have already been made to make progress in this field are presented in
summarized form in this article.
PMID- 25119865
TI - History of knee injury and MRI-assessed knee structures in middle- and older-aged
adults: a cross-sectional study.
AB - The aim of this cross-sectional study was to describe the associations between
history of knee injury and knee structure using magnetic resonance imaging (MRI).
This study included two population-based samples: the Tasmanian Older Adult
Cohort (TASOAC) study (n = 430; mean age, 63.0 years; range, 51-79 years; 51 %
female) and the Offspring study (n = 372; mean age, 45.0 years; range, 26-61
years; 57.5 % female). In both studies, 1.5 T MRI scans of the right knee were
performed to measure bone marrow lesions (BMLs), cartilage volume, tibial bone
area, cartilage defects and meniscal pathology. History of knee injury was
assessed using a self-administered questionnaire. The association between knee
injury and knee structure was determined using multiple linear and log binomial
regression models. Nineteen percent of the middle-aged and 12 % of the older
adults reported a history of knee injury. In middle-aged adults, BML presence
(prevalence ratio (PR) = 1.6 (95 % CI, 1.2; 2.1)), tibial bone area (difference
of means (DM) = +86 (+23, +149)) and meniscal extrusion presence (PR = 2.7 (1.1,
6.8)) were significantly higher in those with knee injury. In older adults,
cartilage defect presence (PR = 1.3 (1.0, 1.7)), lateral (DM = -265 (-439, -92))
and total tibial (DM = -325 (-600, -51)) cartilage volume, BML presence (PR = 1.4
(1.0, 1.9)) and tibial bone area (DM = +140 (+19, +260)) were significantly
associated with knee injury. Meniscal tears showed no significant associations in
either cohorts. The association between knee injury and MRI-assessed structural
pathology in the knee joint is moderate and appears to be stronger in older
adults compared to middle-aged adults.
PMID- 25119867
TI - Oleuropein offers cardioprotection in rats with acute myocardial infarction.
AB - Myocardial infarction causes a cascade of events, which leads to heart failure,
debilitation and death. This study examined possible cardioprotective effect of
oleuropein in rats with acute myocardial infarction. Male Sprague-Dawly rats were
allocated to five groups: sham, myocardial infarction receiving vehicle, and
three myocardial infarction receiving oleuropein at 10, 20, and 30 mg/kg/day for
7 days, and underwent sham operation or coronary ligation. Twenty-four hours
later, animals underwent echocardiographic and hemodynamic studies, and infarct
areas, serum concentrations of oxidative stress and inflammatory markers were
determined. Myocardial infarction group receiving vehicle had significantly lower
left ventricular developed and systolic pressures, rate of rise/decrease of left
ventricular pressure, stroke volume, ejection fraction and cardiac output, and
serum superoxide dismutase and glutathione reductase than those of sham group.
Pretreatment with oleuropein prevented the reduction of these variables.
Moreover, the group had a significantly higher serum malondialdehyde, interleukin
1beta, TNF-alpha, creatin kinase-MB, and troponin I, lactate dehydrogenase, and
infarct area than those of sham group. Pretreatment with oleuropein prevented the
increase of these variables. The findings indicate that coronary ligation results
in acute myocardial infarction characterized by impaired cardiac function, and
oleuropein pretreatment prevented cardiac impairment partly by reducing oxidative
stress and release of proinflammatory cytokines.
PMID- 25119868
TI - High-density single nucleotide polymorphism (SNP) array mapping in Brassica
oleracea: identification of QTL associated with carotenoid variation in broccoli
florets.
AB - KEY MESSAGE: A high-resolution genetic linkage map of B. oleracea was developed
from a B. napus SNP array. The work will facilitate genetic and evolutionary
studies in Brassicaceae. A broccoli population, VI-158 * BNC, consisting of 150
F2:3 families was used to create a saturated Brassica oleracea (diploid: CC)
linkage map using a recently developed rapeseed (Brassica napus) (tetraploid:
AACC) Illumina Infinium single nucleotide polymorphism (SNP) array. The map
consisted of 547 non-redundant SNP markers spanning 948.1 cM across nine
chromosomes with an average interval size of 1.7 cM. As the SNPs are anchored to
the genomic reference sequence of the rapid cycling B. oleracea TO1000, we were
able to estimate that the map provides 96 % coverage of the diploid genome.
Carotenoid analysis of 2 years data identified 3 QTLs on two chromosomes that are
associated with up to half of the phenotypic variation associated with the
accumulation of total or individual compounds. By searching the genome sequences
of the two related diploid species (B. oleracea and B. rapa), we further
identified putative carotenoid candidate genes in the region of these QTLs. This
is the first description of the use of a B. napus SNP array to rapidly construct
high-density genetic linkage maps of one of the constituent diploid species. The
unambiguous nature of these markers with regard to genomic sequences provides
evidence to the nature of genes underlying the QTL, and demonstrates the value
and impact this resource will have on Brassica research.
PMID- 25119869
TI - The detection of a de novo allele of the Glu-1Dx gene in wheat-rye hybrid
offspring.
AB - KEY MESSAGE: This study provides a link between a de novo gene and novel
phenotype in wheat-rye hybrids that can be used as a model for induced de novo
genetic variation. Wide hybridization can produce de novo DNA variation that may
cause novel phenotypes. However, there is still a lack of specific links between
changed genes and novel phenotypes in wide hybrids. The well-studied high
molecular-weight glutenin subunit (HMW-GS) genes in tribe Triticeae provide a
useful model for addressing this issue. In this study, we investigated the
feasibility of a wheat-rye hybridization method for inducing de novo phenotypes
using the Glu-1Dx2.2 subunit as an example. We developed three hexaploid wheat
lines with normal fertility and a Glu-1Dx2.2 variant, named Glu-1Dx2.2 (v) ,
derived from three F1 hybrids. The wild-type Glu-1Dx2.2 has two direct repeats of
295 bp length separated by an intervening 101 bp in its central repetitive
region. In the mutant Glu-1Dx2.2 (v) , one copy of the repeats and the
intervening sequence were deleted, probably through homology-dependent
illegitimate recombination (IR). This study provides a direct link between a de
novo allele and novel phenotype. Our results indicate that the wheat-rye method
may be a useful tool to induce de novo genetic variations that broaden the
genetic diversity for wheat improvement.
PMID- 25119870
TI - Next generation genetic mapping of the Ligon-lintless-2 (Li2) locus in upland
cotton (Gossypium hirsutum L.).
AB - KEY MESSAGE: Mapping-by-sequencing and novel subgenome-specific SNP markers were
used to fine map the Ligon-lintless 2 ( Li 2 ) short-fiber gene in tetraploid
cotton. These methodologies will accelerate gene identification in polyploid
species. Next generation sequencing offers new ways to identify the genetic
mechanisms that underlie mutant phenotypes. The release of a reference diploid
Gossypium raimondii (D5) genome and bioinformatics tools to sort tetraploid reads
into subgenomes has brought cotton genetic mapping into the genomics era. We used
multiple high-throughput sequencing approaches to identify the relevant region of
reference sequence and identify single nucleotide polymorphisms (SNPs) near the
short-fiber mutant Ligon-lintless 2 (Li 2) gene locus. First, we performed RNAseq
on 8-day post-anthesis (DPA) fiber cells from the Li 2 mutant and its wild type
near isogenic line (NIL) Gossypium hirsutum cv. DP5690. We aligned sequence reads
to the D5 genome, sorted the reads into A and D subgenomes with PolyCat and
called SNPs with InterSNP. We then identified SNPs that would result in non
synonymous substitutions to amino acid sequences of annotated genes. This step
allowed us to identify a 1-Mb region with 24 non-synonymous SNPs, representing
the introgressed region that differentiates Li 2 from its NIL. Next, we sequenced
total DNA from pools of F2 plants, using a super bulked segregant analysis
sequencing (sBSAseq) approach. The sBSAseq predicted 82 non-synonymous SNPs among
3,494 SNPs in a 3-Mb region that includes the region identified by RNAseq. We
designed subgenome-specific SNP markers and tested them in an F2 population of
1,733 individuals to construct a genetic map. Our resulting genetic interval
contains only one gene, an aquaporin, which is highly expressed in wild-type
fibers and is significantly under-expressed in elongating Li 2 fiber cells.
PMID- 25119871
TI - An extensive analysis of the African rice genetic diversity through a global
genotyping.
AB - KEY MESSAGE: We present here the first curated collection of wild and cultivated
African rice species. For that, we designed specific SNPs and were able to
structure these very low diverse species. Oryza glaberrima, the cultivated
African rice, is endemic from Africa. This species and its direct ancestor, O.
barthii, are valuable tool for improvement of Asian rice O. sativa in terms of
abiotic and biotic stress resistance. However, only a few limited studies about
the genetic diversity of these species were performed. In the present paper, and
for the first time at such extend, we genotyped 279 O. glaberrima, selected both
for their impact in current breeding and for their geographical distribution, and
101 O. barthii, chosen based on their geographic origin, using a set of 235 SNPs
specifically designed for African rice diversity. Using those data, we were able
to structure the individuals from our sample in three populations for O. barthii,
related to geography, and two populations in O. glaberrima; these two last
populations cannot be linked however to any currently phenotyped trait. Moreover,
we were also able to identify misclassification in O. glaberrima as well as in O.
barthii and identified new form of O. sativa from the set of African varieties.
PMID- 25119872
TI - Gene-based SNP discovery and genetic mapping in pea.
AB - KEY MESSAGE: Gene-based SNPs were identified and mapped in pea using five
recombinant inbred line populations segregating for traits of agronomic
importance. Pea (Pisum sativum L.) is one of the world's oldest domesticated
crops and has been a model system in plant biology and genetics since the work of
Gregor Mendel. Pea is the second most widely grown pulse crop in the world
following common bean. The importance of pea as a food crop is growing due to its
combination of moderate protein concentration, slowly digestible starch, high
dietary fiber concentration, and its richness in micronutrients; however, pea has
lagged behind other major crops in harnessing recent advances in molecular
biology, genomics and bioinformatics, partly due to its large genome size with a
large proportion of repetitive sequence, and to the relatively limited investment
in research in this crop globally. The objective of this research was the
development of a genome-wide transcriptome-based pea single-nucleotide
polymorphism (SNP) marker platform using next-generation sequencing technology. A
total of 1,536 polymorphic SNP loci selected from over 20,000 non-redundant SNPs
identified using deep transcriptome sequencing of eight diverse Pisum accessions
were used for genotyping in five RIL populations using an Illumina GoldenGate
assay. The first high-density pea SNP map defining all seven linkage groups was
generated by integrating with previously published anchor markers. Syntenic
relationships of this map with the model legume Medicago truncatula and lentil
(Lens culinaris Medik.) maps were established. The genic SNP map establishes a
foundation for future molecular breeding efforts by enabling both the
identification and tracking of introgression of genomic regions harbouring QTLs
related to agronomic and seed quality traits.
PMID- 25119874
TI - A study on usefulness evaluation of SUV measured in mini-PACS for each one of
PET/CT equipment.
AB - To save and analyze the data from a positron emission tomography/computed
tomography (PET/CT) scan, it is sometimes important to use a server away from the
workstation of the equipment or to install and operate mini-picture archiving and
communication system (PACS). Mini-PACS was developed to save the data from a scan
and measure the standard uptake value (SUV) in PACS that could be measured only
in PET/CT equipment manufactured by many companies. Against this background, this
study examined whether the SUV measured in PET/CT equipment was the same value in
mini-PACS. This study evaluated Biograph 16 and Biograph 40 manufactured by
SIEMENS and Discovery Ste 8 manufactured by GE, all of which are installed in
this hospital. The SUV of the aorta of 30 patients, who had undergone an (18)F
FDG whole body PET scan in the period from February to October 2012, was measured
at the height of the liver and mediastinum. In the mini-PACS program, the SUV was
also measured and analyzed in an image with the same phase. According to the
study results, the coefficient of the SUV of the liver in PET/CT equipment and
mini-PACS was 0.99, 0.98, and 0.64 in Biograph 16, Biograph 40, and Discovery Ste
8, respectively, where the coefficient of the SUV of aorta was 0.98, 0.98, and
0.66 in Biograph 16, Biograph 40, and Discovery Ste 8, showing a positive
correlation in all equipment.
PMID- 25119873
TI - A high-resolution linkage map of the Rfd1, a restorer-of-fertility locus for
cytoplasmic male sterility in radish (Raphanus sativus L.) produced by a
combination of bulked segregant analysis and RNA-Seq.
AB - KEY MESSAGE: We utilized a combination of BSA and RNA-Seq to identify SNPs linked
to the Rfd1 locus, a restorer-of-fertility gene in radish. A high-density linkage
map was constructed using this approach. Male fertility of cytoplasmic male
sterility conditioned by the Dongbu cytoplasmic and genic male-sterility
cytoplasm can be restored by a restorer-of-fertility locus, Rfd1, in radish. To
construct a high-density linkage map and to identify a candidate gene for the
Rfd1 locus, bulked segregant analysis and RNA-seq approaches were combined. A
total of 26 and 28 million reads produced from male-fertile and male-sterile
bulked RNA were mapped to the radish reference unigenes. After stringent
screening of SNPs, 327 reliable SNPs of 109 unigenes were selected. Arabidopsis
homologs for 101 of the 109 genes were clustered around the 4,000 kb region of
Arabidopsis chromosome 3, which was syntenic to the Rfd1 flanking region. Since
the reference unigene set was incomplete, the contigs were de novo assembled to
identify 134 contigs harboring SNPs. Most of SNP-containing contigs were also
clustered on the same syntenic region in Arabidopsis chromosome. A total of 21
molecular markers positioned within a 2.1 cM interval including the Rfd1 locus
were developed, based on the selected unigenes and contigs. A segregating
population consisting of 10,459 individuals was analyzed to identify recombinants
containing crossovers within this interval. A total of 284 identified
recombinants were then used to construct a high-density map, which delimited the
Rfd1 locus into an 83-kb syntenic interval of Arabidopsis chromosome 3. Since no
candidate gene, such as a pentatricopeptide repeat (PPR)-coding gene, was found
in this interval, 231 unigenes and 491 contigs containing putative PPR motifs
were analyzed further, but no PPR gene in linkage disequilibrium with the Rfd1
locus could be found.
PMID- 25119875
TI - The effect of caste and reproductive state on the chemistry of the cephalic
labial glands secretion of Bombus terrestris.
AB - The cephalic labial glands are well developed in many bee species. In bumble bee
males, they cover most of the head volume, and their secretion is used in marking
reproductive territories and attracting virgin queens. In females, however, they
are poorly studied. Here, we present chemical analyses of their secretion in
queens and workers of Bombus terrestris under various social conditions. The
secretion revealed a context-dependent composition with sterile females
possessing large amounts of fatty acid dodecyl esters, ranging from dodecyl
hexanoate to dodecyl oleate, compared to small amounts in fertile females.
Significant reduction in the dodecyl esters also was found in queens at the
competition phase, where worker reproduction, aggression, and gyne
differentiation occur. The exclusive production of esters by sterile individuals
also is typical of Dufour's gland secretion in this species, albeit in this case
these are octyl rather than dodecyl esters, and the differences between sterile
and fertile individuals are qualitative rather than quantitative. We propose that
the labial gland esters provide yet another signal of reproductive inactivity. In
virgin queens, it may signal that egg laying is deferred to the next season,
while in workers it reinforces the message "I am sterile and out of the
reproductive competition". Whether the reduction in dodecyl esters in fertile
queens as a function of colony social development is involved in regulating gyne
production and the onset of the competition phase is yet to be deciphered.
PMID- 25119876
TI - A pilot study of a new spectrophotometry device to measure tissue oxygen
saturation.
AB - Tissue oxygen saturation (SO2) measurements have the potential for far wider use
than at present but are limited by device availability and portability for many
potential applications. A device based on a small, low-cost general-purpose
spectrophotometer (the Harrison device) might facilitate wider use. The aim of
this study was to compare the Harrison device with a commercial instrument, the
LEA O2C.Measurements were carried out on the forearm and finger of 20 healthy
volunteers, using a blood pressure cuff on the upper arm to induce different
levels of oxygenation. Repeatability of both devices was assessed, and the Bland
Altman method was used to assess agreement between them.The devices showed
agreement in overall tracking of changes in SO2. Test-retest agreement for the
Harrison device was worse than for O2C, with SD repeatability of 10.6% (forearm)
or 18.6% (finger). There was no overall bias between devices, but mean (SD)
difference of 1.2 (11.8%) (forearm) or 4.4 (11.5%) (finger) were outside of a
clinically acceptable range.Disagreements were attributed to the stability of the
Harrison probe and the natural SO2 variations across the skin surface increasing
the random error. Therefore, though not equivalent to the LEA O2C, a probe
redesign and averaged measurements may help establish the Harrison device as a
low cost alternative.
PMID- 25119877
TI - Fecal impaction.
AB - Fecal impaction (FI) is a common and potentially serious medical condition that
occurs in all age groups. Children, incapacitated patients, and the
institutionalized elderly are considered the highest at-risk populations. FI
usually occurs in the setting of chronic or severe constipation, anatomic
anorectal abnormalities, and neurogenic or functional gastrointestinal disorders.
Generally, FI is a preventable disorder, and early recognition is important, as
it is associated with increased morbidity, mortality, and high health care costs.
Evaluation with a careful history and physical examination, in conjunction with
radiologic imaging, such as an acute abdominal series or computed tomography
(CT), is imperative. Prompt identification and treatment minimize the risk of
complications attributable to FI, which may include bowel obstruction leading to
stercoral ulcer, perforation, peritonitis, or cardiopulmonary collapse with
hemodynamic instability. Treatment options include manual fragmentation and
extraction of the fecal mass, distal colonic cleansing using enemas and rectal
lavage with the aid of a sigmoidoscope, and/or using water-soluble contrast media
such as Gastrografin to both identify the extent of the impaction and aid in
cleansing and removal. Surgical resection of the involved colon or rectum is
reserved for peritonitis resulting from bowel perforation. Since recurrence is
common, implementing preventive measures such as increasing daily water and fiber
intake, limiting medications that decrease colonic motility, using secretagogues
or prokinetic agents, and treating underlying anatomic defects are highly
important.
PMID- 25119878
TI - MicroRNAs as modulators and biomarkers of inflammatory and neuropathic pain
conditions.
AB - The post-transcriptional regulator molecules, microRNAs, have emerged as
important biomarkers and modulators of numerous pathophysiological processes
including oncogenesis and cardiovascular diseases. Recently, a significant number
of dysregulations in microRNAs have been reported in patients suffering from
painful disorders such as complex regional pain syndrome, cystitis-induced
chronic pain and irritable bowel disorder, in both affected tissues and the
circulation. Moreover, microRNAs are known to be involved in pain processing
based on several recent findings in animal models of inflammatory and neuropathic
pain. The basis of this review was to cover and summarize available articles in
English encompassing "microRNA and pain". In animal pain models widespread
microRNA modulation is present and manifests on multiple levels i.e.: the dorsal
root ganglia, the spinal dorsal horn and the brain. Numerous functional in vivo
studies have found that dysregulated microRNAs are involved in the post
transcriptional modulation of genes implicated in pain generation and
maintenance. Lastly, a few animal studies have delivered promising results as to
the possibility of applying microRNAs as therapeutics to alleviate established
pain and several clinical studies have highlighted the potential in applying
microRNAs as biomarkers in painful conditions such as complex regional pain
syndrome and fibromyalgia. This review briefly introduces the basics of
microRNAs, their biogenesis and function, and mainly focuses on the recent
advances made in understanding the role of microRNAs in relation to pain
processing and painful conditions. It also provides an overview of widely diverse
methodological approaches and results with a potential for future implications of
microRNAs in the diagnosis and treatment of pain.
PMID- 25119879
TI - The oral commensal Streptococcus mitis shows a mixed memory Th cell signature
that is similar to and cross-reactive with Streptococcus pneumoniae.
AB - BACKGROUND: Carriage of and infection with Streptococcus pneumoniae is known to
predominantly induce T helper 17 (Th17) responses in humans, but the types of Th
cells showing reactivity towards commensal streptococci with low pathogenic
potential, such as the oral commensals S. mitis and S. salivarius, remain
uncharacterized. METHODS: Memory CD4(+) T helper (Th) cell subsets were isolated
from healthy human blood donors according to differential expression of chemokine
receptors, expanded in vitro using polyclonal stimuli and characterized for
reactivity against different streptococcal strains. RESULTS: Th cells responding
to S. mitis, S. salivarius and S. pneumoniae were predominantly in a
CCR6(+)CXCR3(+) subset and produced IFN-gamma, and in a CCR6(+)CCR4(+) subset and
produced IL-17 and IL-22. Frequencies of S. pneumoniae-reactive Th cells were
higher than frequencies of S. mitis- and S. salivarius-specific Th cells. S.
mitis and S. pneumoniae isogenic capsule knock-out mutants and a S. mitis mutant
expressing the serotype 4 capsule of S. pneumoniae showed no different Th cell
responses as compared to wild type strains. S. mitis-specific Th17 cells showed
cross-reactivity with S. pneumoniae. CONCLUSIONS: As Th17 cells partly control
clearance of S. pneumoniae, cross-reactive Th17 cells that may be induced by
commensal bacterial species may influence the immune response, independent of
capsule expression.
PMID- 25119880
TI - Atrial fibrillation as a marker of occult cancer.
AB - BACKGROUND: Recent studies suggest that cancer increases risk of atrial
fibrillation. Whether atrial fibrillation is a marker for underlying occult
cancer is unknown. METHODS: We conducted a cohort study (1980-2011) of all Danish
patients with new-onset atrial fibrillation. To examine cancer risk, we computed
absolute risk at 3 months and standardized incidence ratios (SIRs) by comparing
observed cancer incidence among patients newly diagnosed with atrial fibrillation
with that expected based on national cancer incidence during the period. RESULTS:
Median follow-up time was 3.4 years among 269 742 atrial fibrillation patients.
Within 3 months of follow-up, 6656 cancers occurred (absolute risk, 2.5%; 95%
confidence intervals [CI], 2.4%-2.5%) versus 1302 expected, yielding a SIR of
5.11; 95% CI, 4.99-5.24. Associations were particularly strong for cancers of the
lung, kidney, colon, ovary, and for non-Hodgkin's lymphoma. The SIR within 3
months of follow-up was 7.02; 95% CI, 6.76-7.28 for metastatic and 3.53; 95% CI,
3.38-3.68 for localized cancer. Beyond 3 months of follow-up, overall cancer risk
was modestly increased (SIR, 1.13; 95% CI, 1.12-1.15). CONCLUSION: Patients with
new-onset atrial fibrillation had a markedly increased relative risk of a cancer
diagnosis within the next three months, however, corresponding absolute risk was
small.
PMID- 25119882
TI - A hybrid model for predicting the prevalence of schistosomiasis in humans of
Qianjiang City, China.
AB - BACKGROUNDS/OBJECTIVE: Schistosomiasis is still a major public health problem in
China, despite the fact that the government has implemented a series of
strategies to prevent and control the spread of the parasitic disease. Advanced
warning and reliable forecasting can help policymakers to adjust and implement
strategies more effectively, which will lead to the control and elimination of
schistosomiasis. Our aim is to explore the application of a hybrid forecasting
model to track the trends of the prevalence of schistosomiasis in humans, which
provides a methodological basis for predicting and detecting schistosomiasis
infection in endemic areas. METHODS: A hybrid approach combining the
autoregressive integrated moving average (ARIMA) model and the nonlinear
autoregressive neural network (NARNN) model to forecast the prevalence of
schistosomiasis in the future four years. Forecasting performance was compared
between the hybrid ARIMA-NARNN model, and the single ARIMA or the single NARNN
model. RESULTS: The modelling mean square error (MSE), mean absolute error (MAE)
and mean absolute percentage error (MAPE) of the ARIMA-NARNN model was 0.1869 *
10(-4), 0.0029, 0.0419 with a corresponding testing error of 0.9375 * 10(-4),
0.0081, 0.9064, respectively. These error values generated with the hybrid model
were all lower than those obtained from the single ARIMA or NARNN model. The
forecasting values were 0.75%, 0.80%, 0.76% and 0.77% in the future four years,
which demonstrated a no-downward trend. CONCLUSION: The hybrid model has high
quality prediction accuracy in the prevalence of schistosomiasis, which provides
a methodological basis for future schistosomiasis monitoring and control
strategies in the study area. It is worth attempting to utilize the hybrid
detection scheme in other schistosomiasis-endemic areas including other
infectious diseases.
PMID- 25119881
TI - Nasal sensitization with ragweed pollen induces local-allergic-rhinitis-like
symptoms in mice.
AB - Recently, the concept of local allergic rhinitis (LAR) was established, namely
rhinitis symptoms with local IgE production and negative serum antigen-specific
IgE. However, the natural course of LAR development and the disease pathogenesis
is poorly understood. This study investigated the pathophysiology of mice with
allergic rhinitis that initially sensitized with ragweed pollen through the nasal
route. Mice were nasally administrated ragweed pollen over consecutive days
without prior systemic immunization of the allergen. Serial nasal sensitization
of ragweed pollen induced an allergen-specific increase in sneezing, eosinophilic
infiltration, and the production of local IgE by day 7, but serum antigen
specific IgE was not detected. Th2 cells accumulated in nose and cervical lymph
nodes as early as day 3. These symptoms are characteristic of human LAR.
Continual nasal exposure of ragweed pollen for 3 weeks resulted in the onset of
classical AR with systemic atopy and adversely affected lung inflammation when
the allergen was instilled into the lung. Fcer1a(-/-) mice were defective in
sneezing but developed normal eosinophilic infiltration. Contrary, Rag2(-/-) mice
were defective in both sneezing and eosinophilic infiltration, suggesting that T
cells play a central role in the pathogenesis of the disease. These observations
demonstrate nasal allergen sensitization to non-atopic individuals can induce
LAR. Because local Th2 cell accumulation is the first sign and Th2 cells have a
central role in the disease, a T-cell-based approach may aid the diagnosis and
treatment of LAR.
PMID- 25119883
TI - Engineered hyperactive integrase for concerted HIV-1 DNA integration.
AB - The DNA cutting and joining reactions of HIV-1 integration are catalyzed by
integrase (IN), a viral protein that functions as a tetramer bridging the two
viral DNA ends (intasome). Two major obstacles for biochemical and structural
studies of HIV-1 intasomes are 1) the low efficiency of assembly with
oligonucleotide DNA substrates, and 2) the non-specific aggregation of both
intasomes and free IN in the reaction mixture. By fusing IN with a small non
specific DNA binding protein, Sulfolobus solfataricus chromosomal protein Sso7d
(PDB: 1BNZ), we have engineered a highly soluble and hyperactive IN. Unlike wild
type IN, it efficiently catalyzes intasome assembly and concerted integration
with oligonucleotide DNA substrates. The fusion IN protein also functions to
integrate viral reverse transcripts during HIV-infection. The hyperactive HIV-1
IN may assist in facilitating future biochemical and structural studies of HIV-1
intasomes. Understanding the mechanistic basis of the Sso7d-IN fusion protein
could provide insight into the factors that have hindered biophysical studies of
wild-type HIV-1 IN and intasomes.
PMID- 25119884
TI - Persistent release of IL-1s from skin is associated with systemic cardio-vascular
disease, emaciation and systemic amyloidosis: the potential of anti-IL-1 therapy
for systemic inflammatory diseases.
AB - The skin is an immune organ that contains innate and acquired immune systems and
thus is able to respond to exogenous stimuli producing large amount of
proinflammatory cytokines including IL-1 and IL-1 family members. The role of the
epidermal IL-1 is not limited to initiation of local inflammatory responses, but
also to induction of systemic inflammation. However, association of persistent
release of IL-1 family members from severe skin inflammatory diseases such as
psoriasis, epidermolysis bullosa, atopic dermatitis, blistering diseases and
desmoglein-1 deficiency syndrome with diseases in systemic organs have not been
so far assessed. Here, we showed the occurrence of severe systemic cardiovascular
diseases and metabolic abnormalities including aberrant vascular wall remodeling
with aortic stenosis, cardiomegaly, impaired limb and tail circulation, fatty
tissue loss and systemic amyloid deposition in multiple organs with liver and
kidney dysfunction in mouse models with severe dermatitis caused by persistent
release of IL-1s from the skin. These morbid conditions were ameliorated by
simultaneous administration of anti-IL-1alpha and IL-1beta antibodies. These
findings may explain the morbid association of arteriosclerosis, heart
involvement, amyloidosis and cachexia in severe systemic skin diseases and
systemic autoinflammatory diseases, and support the value of anti-IL-1 therapy
for systemic inflammatory diseases.
PMID- 25119885
TI - Large artery stiffness and carotid intima-media thickness in relation to markers
of calcium and bone mineral metabolism in African women older than 46 years.
AB - Vascular calcification and cardiovascular diseases have been associated with
altered bone metabolism. We explored the relationships of arterial pressures and
carotid intima-media thickness (CIMT) with parathyroid hormone, 25
hydroxycholecalciferol and their ratio (PTH:25(OH)D3) as well as a marker of bone
resorption (CTX) in lean and overweight/obese African women. A population of 434
African women older than 46 years was divided into lean and overweight/obese
groups. We assessed brachial blood pressure, central pulse pressure (cPP) and
CIMT, and determined PTH, 25(OH)D3 and CTX concentrations. Overweight/obese women
had elevated PTH and PTH:25(OH)D3 compared with lean women (both P<0.001),
whereas lean women had higher CTX (P<0.001). Single, partial and multiple
regression analyses indicated that, in lean women CIMT was independently
associated with PTH:25(OH)D3 (R(2)=0.22; beta=0.26; P=0.003), whereas in obese
women cPP was associated with both PTH:25(OH)D3 (R2=0.20; beta=0.17; P=0.017) and
CTX (R2=0.20; beta=0.17; P=0.025). In conclusion, we found that in African women
with increased adiposity, cPP (as a surrogate measure of arterial stiffness), was
positively associated with alterations in bone metabolism and calciotropic
hormones, whereas CIMT of lean women was positively associated with PTH:25(OH)D3.
Our results suggest that alterations in bone and calcium metabolism may
contribute to arterial calcification in older African women.
PMID- 25119886
TI - Association between undiagnosed hypertension and microalbuminuria in South Asians
without known diabetes.
AB - Data suggest increased rates of chronic kidney disease (CKD) in those with
undiagnosed hypertension (HTN). Our study aimed to determine the prevalence of
CKD in undiagnosed hypertensives in a previously unreported subgroup of
individuals of South Asian ethnicity. We analysed data from subjects in the
ADDITION-Leicester study, a UK based multiethnic, community diabetes screening
study. Standard definitions included: HTN-mean recorded BP of ?140/90 mm Hg, CKD
stage 3 and above-estimated glomerular filtration rate (eGFR) <60 ml min(-1) per
1.73 m2 and microalbuminuria as albumin creatinine ratio ?3 mg mmol(-1). Logistic
regression was performed with age, gender and body mass index (kg m(-2)) as co
variates. 6082 individuals (52.5% female, mean age, 57.2 years; White European,
77.8% and South Asian, 22.0%), 31.1% had undiagnosed HTN. Overall, individuals
with undiagnosed HTN compared with normotensives had an odds ratio for
microalbuminuria of 2.24 (95% confidence interval (CI): 1.72-2.94). For South
Asians, the odds ratio was 3.81. (95% CI: 2.24-6.47) for microalbuminuria with a
trend towards an eGFR<60 ml min(-1) per 1.73 m2. Future studies should consider
intensified screening for HTN to refine the population suitable for CKD
screening, particularly in the South Asian ethnic group.
PMID- 25119887
TI - Accelerated analysis of three-dimensional blood flow of the thoracic aorta in
stroke patients.
AB - To test if new software accelerates analysis of in vivo acquired 4D flow MRI
data. Respiration-gated and ECG-synchronized 4D flow MRI of the aorta was
performed in 20 stroke patients using a routine 3-Tesla MRI system (TIMTRIO,
Siemens, Germany). 3D blood flow data was processed by one experienced observer
using new (A = MEVISFlow) and widely-used software (B = EnSight + Velomap
/FlowTool). Evaluation included: inter-/intra-observer variability of software A
and inter-software comparison regarding (1) blood flow quantification (total
/peak flow) and (2) flow visualisation, plus (3) measurement of the time required
for visualization and quantification of data (software A&B). (1) Inter-/intra
observer agreement of software A (mean difference <=5.2 and <=0.9 %,
respectively) and inter-software agreement (mean difference <= 2.2 %) was high
with high correlation of peak and total blood flow (r >= 0.74; p < 0.001 and r >=
0.91; p < 0.001). (2) Comparison of blood flow visualization showed substantial
agreement (kappa >= 0.68). (3) Data-analysis was three times faster when using
software A [18:10 (+/-1:29) vs. 58:30 (+/-5:28) min; p < 0.0001]. Acceleration of
blood flow quantification and visualisation using new software strongly
facilitates future applications of 4D flow MRI and thus enables its usage in
larger patient cohorts in clinical research and routine.
PMID- 25119888
TI - High-pitch prospective ECG-triggered helical coronary computed tomography
angiography in clinical practice: image quality and radiation dose.
AB - High-pitch prospective ECG-triggered helical (PTH) protocols for coronary
computed tomography angiography (CCTA) have demonstrated adequate image quality
(IQ) in small-scaled studies and highly selected patients. Clinical applicability
in a general clinical population is uncertain. This study evaluated the
implementation of a PTH protocol in a routine clinical cohort, focusing on IQ and
radiation dose. The local scientific board approved the retrospective analysis
and all patients signed an informed consent statement for usage of their data. In
consecutive patients suspected of coronary artery disease CCTA was performed
using a dual source 128-slice scanner. All patients with a regular heart rate <65
bpm underwent a PTH CCTA. IQ for each coronary segment was graded (1 = absence of
artifacts to 4 = non-evaluable). In 664 (80.4 %) of 826 included patients [mean
age +/- standard deviation (SD) 57 +/- 11, 65 % female, mean body mass index
(BMI) +/- SD 27 +/- 9 kg m(-2)] PTH CCTA was acquired whereas in 162 (19.6 %) a
non-PTH sequence was used. Reasons for not performing a PTH protocol were
persistent high heart rate (41.6 %) or heart rate irregularity (58.4 %). Mean +/-
SD heart rates for PTH and non-PTH CCTA were 55 +/- 5 and 65 +/- 9 bpm,
respectively, p < 0.001. In the PTH group 92 % of the segments were of diagnostic
quality (score 1-3), versus 87 % in the non-PTH group (p = 0.055). Per patient,
mean IQ score was 1.19 and 1.21 respectively (lower is better; p = 0.012).
Effective dose (including topogram, test bolus, and coronary calcium score), as
calculated with a conversion factor of 0.014 mSv mGy(-1) cm(-1) was 1.6 +/- 0.6
and 4.7 +/- 2.6 mSv for the PTH and the non-PTH group respectively, (p < 0.001).
Performing high-pitch PTH sequences on a routine basis is feasible in the
majority of patients with high IQ and significant reduction in radiation dose.
PMID- 25119889
TI - Computed tomography for planning and postoperative imaging of transvenous mitral
annuloplasty: first experience in an animal model.
AB - To investigate the use of computed tomography (CT) to measure the mitral valve
annulus size before implantation of a percutaneous mitral valve annuloplasty
device in an animal trial. Seven domestic pigs underwent CT before and after
implantation of a CardiobandTM (a percutaneously implantable mitral valve
annuloplasty device) with a second-generation 128-section dual-source CT machine.
Implantation of the CardiobandTM was performed in a standard fashion according to
a protocol. Animals were sacrificed afterwards and the hearts explanted. The
CardiobandTM was found to be adequately implanted in all animals, with no anchor
dehiscence and no damage of the circumflex artery (CX) or the coronary sinus
(CS). The correct length of the band as chosen according to the length of the
posterior mitral annulus measured in CT before implantation was confirmed in
gross examination in all animals. The device did not result in a metal artifact
related degradation of image quality. The closest distance from the closest
anchor to the CX was 2.1 +/- 0.7 mm in diastole and 1.6 +/- 0.5 mm systole.
Mitral annulus distance to the CS was 6.4 +/- 1.3 mm in diastole and 7.7 +/- 1.1
mm in systole. CT visualization and measurement of the mitral valve annulus
dimensions is feasible and can become the imaging method of choice for procedure
planning of CardiobandTM implantations or other transcatheter mitral annuloplasty
devices.
PMID- 25119891
TI - Annual report SWEDEHEART 2012.
PMID- 25119892
TI - Characteristics of childbearing women, obstetrical interventions and preterm
delivery: a comparison of the US and France.
AB - Preterm delivery rates have remained consistently higher in the US than France,
but the reasons for this excess remain poorly understood. We examined if
differences in socio-demographic risk factors or more liberal use of obstetrical
interventions contributed to higher rates in the US. Data on singleton live
births in 1995, 1998 and 2003 from US birth certificates and the French National
Perinatal Survey were used to analyze preterm delivery rate by maternal
characteristics (age, parity, marital status, education, race (US)/nationality
(France), prenatal care and smoking). We distinguished between preterm deliveries
with a cesarean or a labor induction and those without these interventions.
Unadjusted and adjusted risk ratios (RR) for the US compared to France were
estimated using log-binomial regression. Preterm delivery rates were 7.9 % in the
US and 4.7 % in France (risk ratio [RR] = 1.7, 95 % confidence interval [CI] 1.6
1.8). The US had more teen mothers and late entry to prenatal care, but fewer
women smoked, although adjustment for these and other confounders did not reduce
RR (1.8, 95 % CI 1.7-1.9). Preterm delivery rates associated with labor induction
or cesarean were 3.3 % in the US and 2.1 % in France (RR 1.6, 95 % CI 1.5-1.7);
the corresponding rates for preterm delivery without these interventions were 4.5
and 2.5 % (RR 1.8, 95 % CI 1.7-1.9), respectively. Key socio-demographic risk
factors and more obstetric intervention do not explain higher US preterm delivery
rates. Avenues for future research include the impact of universal access to
health services (universal health insurance?) on health care quality and the
association between more generous social policies, stress and the risks of
preterm delivery.
PMID- 25119890
TI - The nuclear envelope: an intriguing focal point for neurogenetic disease.
AB - Mutations in genes encoding nuclear envelope proteins cause a wide range of
inherited diseases, many of which are neurological. We review the genetic causes
and what little is known about pathogenesis of these nuclear envelopathies that
primarily affect striated muscle, peripheral nerve and the central nervous
system. We conclude by providing examples of experimental therapeutic approaches
to these rare but important neuromuscular diseases.
PMID- 25119893
TI - Assessing strategies for heart failure with preserved ejection fraction at the
outpatient clinic.
AB - BACKGROUND: Heart failure with preserved ejection fraction (HFPEF) is the most
common form of heart failure (HF), its diagnosis being a challenge to the
outpatient clinic practice. OBJECTIVE: To describe and compare two strategies
derived from algorithms of the European Society of Cardiology Diastology
Guidelines for the diagnosis of HFPEF. METHODS: Cross-sectional study with 166
consecutive ambulatory patients (67.9+/-11.7 years; 72% of women). The strategies
to confirm HFPEF were established according to the European Society of Cardiology
Diastology Guidelines criteria. In strategy 1 (S1), tissue Doppler
echocardiography (TDE) and electrocardiography (ECG) were used; in strategy 2
(S2), B-type natriuretic peptide (BNP) measurement was included. RESULTS: In S1,
patients were divided into groups based on the E/E'ratio as follows: GI, E/E'> 15
(n = 16; 9%); GII, E/E'8 to 15 (n = 79; 48%); and GIII, E/E'< 8 (n = 71; 43%).
HFPEF was confirmed in GI and excluded in GIII. In GII, TDE [left atrial volume
index (LAVI) >= 40 mL/m2; left ventricular mass index LVMI) > 122 for women and >
149 g/m2 for men] and ECG (atrial fibrillation) parameters were assessed,
confirming HFPEF in 33 more patients, adding up to 49 (29%). In S2, patients were
divided into three groups based on BNP levels. GI (BNP > 200 pg/mL) consisted of
12 patients, HFPEF being confirmed in all of them. GII (BNP ranging from 100 to
200 pg/mL) consisted of 20 patients with LAVI > 29 mL/m2, or LVMI >= 96 g/m2 for
women or >= 116 g/m2 for men, or E/E'>= 8 or atrial fibrillation on ECG, and the
diagnosis of HFPEF was confirmed in 15. GIII (BNP < 100 pg/mL) consisted of 134
patients, 26 of whom had the diagnosis of HFPEF confirmed when GII parameters
were used. Measuring BNP levels in S2 identified 4 more patients (8%) with HFPEF
as compared with those identified in S1. CONCLUSION: The association of BNP
measurement and TDE data is better than the isolated use of those parameters. BNP
can be useful in identifying patients whose diagnosis of HF had been previously
excluded based only on TDE findings.
PMID- 25119894
TI - Ivabradine improves heart rate variability in patients with nonischemic dilated
cardiomyopathy.
AB - BACKGROUND: Ivabradine is a novel specific heart rate (HR)-lowering agent that
improves event-free survival in patients with heart failure (HF). OBJECTIVES: We
aimed to evaluate the effect of ivabradine on time domain indices of heart rate
variability (HRV) in patients with HF. METHODS: Forty-eight patients with
compensated HF of nonischemic origin were included. Ivabradine treatment was
initiated according to the latest HF guidelines. For HRV analysis, 24-h Holter
recording was obtained from each patient before and after 8 weeks of treatment
with ivabradine. RESULTS: The mean RR interval, standard deviation of all normal
to normal RR intervals (SDNN), the standard deviation of 5-min mean RR intervals
(SDANN), the mean of the standard deviation of all normal-to-normal RR intervals
for all 5-min segments (SDNN index), the percentage of successive normal RR
intervals exceeding 50 ms (pNN50), and the square root of the mean of the squares
of the differences between successive normal to normal RR intervals (RMSSD) were
low at baseline before treatment with ivabradine. After 8 weeks of treatment with
ivabradine, the mean HR (83.6 +/- 8.0 and 64.6 +/- 5.8, p < 0.0001), mean RR
interval (713 +/- 74 and 943 +/- 101 ms, p < 0.0001), SDNN (56.2 +/- 15.7 and
87.9 +/- 19.4 ms, p < 0.0001), SDANN (49.5 +/- 14.7 and 76.4 +/- 19.5 ms, p <
0.0001), SDNN index (24.7 +/- 8.8 and 38.3 +/- 13.1 ms, p < 0.0001), pNN50 (2.4
+/- 1.6 and 3.2 +/- 2.2 %, p < 0.0001), and RMSSD (13.5 +/- 4.6 and 17.8 +/- 5.4
ms, p < 0.0001) substantially improved, which sustained during both when awake
and while asleep. CONCLUSION: Our findings suggest that treatment with ivabradine
improves HRV in nonischemic patients with HF.
PMID- 25119895
TI - Left atrial volume index and prediction of events in acute coronary syndrome:
Solar Registry.
AB - BACKGROUND: According to some international studies, patients with acute coronary
syndrome (ACS) and increased left atrial volume index (LAVI) have worse long-term
prognosis. However, national Brazilian studies confirming this prediction are
still lacking. OBJECTIVE: To evaluate LAVI as a predictor of major cardiovascular
events (MCE) in patients with ACS during a 365-day follow-up. METHODS:
Prospective cohort of 171 patients diagnosed with ACS whose LAVI was calculated
within 48 hours after hospital admission. According to LAVI, two groups were
categorized: normal LAVI (<= 32 mL/m2) and increased LAVI (> 32 mL/m2). Both
groups were compared regarding clinical and echocardiographic characteristics, in
and out-of-hospital outcomes, and occurrence of ECM in up to 365 days. RESULTS:
Increased LAVI was observed in 78 patients (45%), and was associated with older
age, higher body mass index, hypertension, history of myocardial infarction and
previous angioplasty, and lower creatinine clearance and ejection fraction.
During hospitalization, acute pulmonary edema was more frequent in patients with
increased LAVI (14.1% vs. 4.3%, p = 0.024). After discharge, the occurrence of
combined outcome for MCE was higher (p = 0.001) in the group with increased LAVI
(26%) as compared to the normal LAVI group (7%) [RR (95% CI) = 3.46 (1.54-7.73)
vs. 0.80 (0.69-0.92)]. After Cox regression, increased LAVI increased the
probability of MCE (HR = 3.08, 95% CI = 1.28-7.40, p = 0.012). CONCLUSION:
Increased LAVI is an important predictor of MCE in a one-year follow-up.
PMID- 25119896
TI - Haplotype analysis of interleukin-10 gene promoter polymorphisms in chronic
hepatitis C infection: a case control study.
AB - High prevalence of hepatitis c virus (HCV) infection in some areas necessitates
more investigations of the causative factors. Genetic factors that cause
disruption in operation or secretion of interleukin 10 (IL-10), an anti
inflammatory cytokine, may play a role in the intensity of the disease. The aim
of this study was to evaluate genetic variants of IL-10 gene polymorphisms in HCV
patients and their relationship with HCV disease. Fifty HCV patients and the same
number of healthy individuals who were referred to hepatitis clinic in Mashhad,
northeast of Iran, were recruited. Genomic DNA was extracted from whole blood.
Genotyping for IL-10 gene promoter polymorphisms in three positions (-1082 G>A,
819 C>T and -592 C>A) was conducted by amplification refractory mutation system
polymerase chain reaction. Haplotype analysis was performed using PHASE software.
In a recessive analysis model of the -1082 position (GG vs. AA+AG), GG genotype
was more common in patients (adjusted p = 0.02; OR = 4.66 [95% CI 1.31-16.35]).
Also, ATA haplotype was more prevalent in HCV patients (adjusted p = 0.061; OR =
1.87 [95% CI 0.97-3.61]). Also, ATC/GCA diplotypes were more common in controls
(adjusted p=0.002; adjusted OR = 0.27 [95% CI 0.11-0.63]). Although we found a
possible association between IL-10 promoter polymorphisms and HCV infection,
certain genotypes or diplotypes may confer a higher risk or susceptibility for
developing HCV infection.
PMID- 25119897
TI - Expression of GOLPH2 is associated with the progression of and poor prognosis in
gastric cancer.
AB - Golgi phosphoprotein 2 (GOLPH2) has been associated with the development and
progression of various human cancers. The aims of this study were to investigate
the relationship between GOLPH2 and gastric cancer (GC) progression and explore
the clinical significance of GOLPH2 in GC. GOLPH2 expression was examined in four
pairs of primary GC tissues and the adjacent non-cancerous tissues from the same
patients, using immunohistochemistry (IHC), quantitative PCR and western
blotting. Furthermore, GOLPH2 protein expression was analyzed in 10 normal
gastric tissues and 385 clinicopathologically characterized cases of GC by IHC.
Statistical analyses were performed to determine the prognostic and diagnostic
associations. GOLPH2 mRNA and protein expression were both markedly upregulated
in GC tissues, compared with the paired adjacent non-cancerous tissues. The Chi
square test and Spearman analysis revealed a significant correlation between
GOLPH2 expression and clinical stage, T classification, lymph node metastasis,
metastasis and venous invasion. Patients with a higher GOLPH2 expression had a
shorter overall survival (OS), compared to patients with lower GOLPH2 expression.
Notably, our results suggested that GOLPH2 is associated with the development and
progression of GC. Therefore, additional studies focusing on the potential of
GOLPH2 as a novel therapeutic target in GC are required.
PMID- 25119898
TI - Desmocollin-2 affects the adhesive strength and cytoskeletal arrangement in
esophageal squamous cell carcinoma cells.
AB - Desmocollin-2 (DSC2), a transmembrane glycoprotein belonging to the desmosomal
cadherin family, has been found to be differentially expressed in several types
of cancer and to be involved in tumor progression. The tumor metastasis
suppressing property of DSC2 in esophageal squamous cell carcinoma (ESCC) has
been described, however, its contribution to cell cohesion in ESCC remains to be
elucidated. In the present study, using RNA interference (RNAi), the expression
of DSC2 was silenced in SHEEC and KYSE510 cells. Hanging drop and fragmentation
assays were performed to investigate the role of DSC2 in cell-cell adhesion.
Western blot analysis and confocal microscopy were used to analyze the expression
and localization of cell adhesion molecules and cytoskeletal arrangement. The
results demonstrated that DSC2 knock down by RNAi caused defects in cell-cell
adhesion and a concomitant reduction in desmosomal protein expression and
adherens junction molecule distribution. A decrease in the expression of DSC2
caused an increase in free gamma-catenin levels, thus promoting its recruitment
to the adherens junction complex. In addition, the RNAi-mediated inhibition of
DSC2 led to keratin intermediate filament retraction and filamentous-actin
cytoskeleton rearrangement. Taken together, these data support our previous
findings and the proposal that DSC2 may be involved in the regulation of the
invasive behavior of cells by a mechanism that controls cell-cell attachment and
cytoskeleton rearrangement.
PMID- 25119899
TI - Inferring the provenance of an alien species with DNA barcodes: the neotropical
butterfly Dryas iulia in Thailand.
AB - The Neotropical butterfly Dryas iulia has been collected from several locations
in Thailand and Malaysia since 2007, and has been observed breeding in the wild,
using introduced Passiflora foetida as a larval host plant. The butterfly is bred
by a butterfly house in Phuket, Thailand, for release at weddings and Buddhist
ceremonies, and we hypothesized that this butterfly house was the source of wild,
Thai individuals. We compared wing patterns and COI barcodes from two, wild Thai
populations with individuals obtained from this butterfly house. All Thai
individuals resemble the subspecies D. iulia modesta, and barcodes from wild and
captive Thai specimens were identical. This unique, Thai barcode was not found in
any of the 30 specimens sampled from the wild in the species' native range, but
is most similar to specimens from Costa Rica, where many exporting butterfly
farms are located. These data implicate the butterfly house as the source of
Thailand's wild D. iulia populations, which are currently so widespread that
eradication efforts are unlikely to be successful.
PMID- 25119901
TI - [Identification of three novel frameshift mutations in the RUNX2 gene in three
sporadic Chinese cases with cleidocranial dysplasia].
AB - OBJECTIVE: To investigate the molecular etiology of three patients with sporadic
cleidocranial dysplasia (CCD) and to provide genetic counseling and prenatal
diagnosis for the family members based on the identified mutations. METHODS:
Genomic DNA was extracted from peripheral blood samples using a standard method.
All 7 coding exons of the RUNX2 gene and their flanking intronic sequences were
amplified by PCR and sequenced directly. The PCR products of the exons with
mutations from the three patients were cloned into a T-vector. Positive clones
were sequenced. RESULTS: The three patients who have the typical CCD phenotypes
involving clavicles, calvarium, stature, and teeth have carried various
frameshift mutations in the RUNX2 gene. Patient 1 has a gross deletion of 80
nucleotides in exon 1 (c.227_306del), which caused a frameshift beginning at the
Q/A repeat of the polypeptide and a premature termination (p.Ala76GlyfsX58).
Patient 2 has a 2-bp duplication in exon 2 (c.471_472dupGG), which also caused a
frameshift and a premature termination (p.Ala158GlyfsX19). Patient 3 has a T
duplication in exon 7 (c.1321dupT), which caused a frameshift and a premature
termination (p.Ser370PhefsX13) as well. CONCLUSION: The three novel mutations in
RUNX2 are the underlying molecular mechanism for the CCD phenotypes of three
sporadic Chinese patients, respectively. These have broadened the mutation
spectrum of RUNX2 gene and provided a molecular basis for the genetic counseling
and prenatal diagnosis for the affected families.
PMID- 25119902
TI - [A novel mutation in GCH1 gene causes dopa-responsive dystonia].
AB - OBJECTIVE: To identify potential mutation of the GCH1 gene in a Chinese family
affected with dopa-responsive dystonia. METHODS: Genomic DNA of patients was
extracted from peripheral blood samples. The 6 exons of the GCH1 gene and at
least 100 bp of flanking intronic sequences were amplified with PCR. Potential
mutations were screened by direct sequencing. Identified mutation was verified
with denaturing high performance liquid chromatography (DHPLC) in 100 healthy
controls. RESULTS: All patients were found to be heterozygous for a novel
c.597delT (p.Ala200LeufsX5) deletion in the exon 5 of the GCH1 gene. The deletion
of T has resulted in formation of a shorter (203 amino acids) truncated non
functional guanosine triphosphate cyclohydrolase I. The same mutation was not
found in the 100 controls. CONCLUSION: A novel GCH1 gene frameshifing mutation
probably underlies the dopa-responsive dystonia in this Chinese family.
PMID- 25119903
TI - [Prenatal genetic diagnosis for two Chinese families affected with oculocutaneous
albinism type II].
AB - OBJECTIVE: To perform genotyping analysis and subsequent prenatal genetic
diagnosis for two families affected with oculocutaneous albinism (OCA). METHODS:
Direct sequencing of TYR and P genes was performed in two albino probands. Family
members were screened for corresponding mutant alleles. Prenatal genetic
diagnoses were performed at early pregnancy by chorionic villus sampling (CVS) at
mid-pregnancy through amniocentesis. RESULTS: No mutations were detected in the
TYR gene in either probands, whereas 4 heterozygous mutations of the P gene were
found, namely c.406C>T, c.535A>G, c.808-2A>G and c.2180T>C, among which c.535A>G
and c.808-2A>G were novel. In the first round prenatal genetic testing, both
fetuses were found to have the same genotypes as the probands. Both families had
decided to terminate the pregnancy after genetic counseling. In the second round
testing, neither of the fetuses was found to be affected by genotyping. The
pregnancies continued and two healthy fetuses were born. CONCLUSION: OCA can be
classified by genotyping, with which reliable prenatal diagnosis and feasible
genetic counseling may be provided.
PMID- 25119900
TI - SSU rDNA divergence in planktonic foraminifera: molecular taxonomy and
biogeographic implications.
AB - The use of planktonic foraminifera in paleoceanography requires taxonomic
consistency and precise assessment of the species biogeography. Yet, ribosomal
small subunit (SSUr) DNA analyses have revealed that most of the modern morpho
species of planktonic foraminifera are composed of a complex of several distinct
genetic types that may correspond to cryptic or pseudo-cryptic species. These
genetic types are usually delimitated using partial sequences located at the
3'end of the SSUrDNA, but typically based on empirical delimitation. Here, we
first use patristic genetic distances calculated within and among genetic types
of the most common morpho-species to show that intra-type and inter-type genetic
distances within morpho-species may significantly overlap, suggesting that
genetic types have been sometimes inconsistently defined. We further apply two
quantitative and independent methods, ABGD (Automatic Barcode Gap Detection) and
GMYC (General Mixed Yule Coalescent) to a dataset of published and newly obtained
partial SSU rDNA for a more objective assessment of the species status of these
genetic types. Results of these complementary approaches are highly congruent and
lead to a molecular taxonomy that ranks 49 genetic types of planktonic
foraminifera as genuine (pseudo)cryptic species. Our results advocate for a
standardized sequencing procedure allowing homogenous delimitations of
(pseudo)cryptic species. On the ground of this revised taxonomic framework, we
finally provide an integrative taxonomy synthesizing geographic, ecological and
morphological differentiations that can occur among the genuine (pseudo)cryptic
species. Due to molecular, environmental or morphological data scarcities, many
aspects of our proposed integrative taxonomy are not yet fully resolved. On the
other hand, our study opens up the potential for a correct interpretation of
environmental sequence datasets.
PMID- 25119904
TI - [Mutation analysis for a family affected with riboflavin responsive-multiple acyl
CoA dehydrogenase deficiency].
AB - OBJECTIVE: To identify pathogenic mutation in a boy affected with riboflavin
responsive-multiple acyl-CoA dehydrogenase deficiency (RR-MADD). METHODS: The
patient was initially diagnosed as primary carnitine deficiency (PCD) and has
been treated with carnitine supplementation for 7 years. Clinical manifestations
and characteristics of fibula muscle specimen were analyzed. Potential mutation
in electron transfer flavoprotein dehydrogenase (ETFDH) gene (for the patient and
his parents) and carnitine transfer protein gene (SLC22A5) (for the patient) was
screened. RESULTS: Electronic microscopy of the muscle specimen has suggested
lipid storage myopathy. Mutation analysis has found that the patient carried
compound heterozygous mutations, c.250G>A and c.380T>C, in exon 3 of the ETFDH
gene, whilst his father and mother were heterozygous for the c.380T>C and
c.250G>A mutations, respectively. Screening of the SLC22A5 gene has yielded no
clinically meaningful result. After the establishment of diagnosis of RR-MADD,
the condition of the patient has improved greatly with supplementation of high
doses of riboflavin along with continuous carnitine supplement. CONCLUSION: The
c.250G>A (p.Ala84Thr) mutation of exon 3 of the ETFDH gene has been a hot spot in
Southern Chinese population, whilst the c.380T>C (p.Leu127Pro) is rarely
reported. Our case has suggested that therapeutic diagnosis cannot substitute
genetic testing. The mechanism for having stabilized the patient with only
carnitine supplementation for 7 years needs further investigation.
PMID- 25119905
TI - [Analysis of 22 patients with congenital cleft lip and palate using high
resolution chromosome microarray].
AB - OBJECTIVE: To assess the value of chromosome microarray analysis (CMA) for
identifying the etiology of patients with congenital cleft lip and palate.
METHODS: Twenty-two patients with no identifiable chromosomal aberrations by
conventional cytogenetic technique were selected. DNA was extracted and
hybridized with Affymetrix CytoScan(TM) HD arrays following the manufacturer's
protocol. The data were analyzed with a CHAS v2.0 software. RESULTS: CMA analysis
has identified submicroscopic copy number variants (CNVs) in all of the cases,
which have ranged from 100 kb to 1.8 Mb. Potential pathogenic CNVs were
identified in 5 patients (22.7%), which involved microdeletions and
microduplications on 8p23.1, 10q22.2-q22.3, 6q26, 20p12.1 and 18q12.3. MYST4,
MACROD2 and SOX7 genes are likely the causative genes. CONCLUSION: CMA is an
effective method for identification of etiology in patients with cleft lip and
palate. CMA should be provided for patients with cleft lip and palate but a
normal karyotype. Especially for those with additional structural abnormalities,
there is a high risk for submicroscopic chromosomal aberrations.
PMID- 25119906
TI - [Establishment and application of quantitative detection for heteroplasmic mtDNA
mutation 3243A->G].
AB - OBJECTIVE: To develop a rapid, simple, cost-effective, accurate and sensitive
method for quantitative detection of mitochondrial DNA (mtDNA) 3243A->G mutation
in order to provide reference for selecting the best detection method under
different conditions. METHODS: Genomic DNA was extracted from peripheral
leucocytes of 17 individuals from a Wenzhou family featuring maternally inherited
diabetes and deafness (MIDD). Heteroplasmic level of mtDNA 3243A->G mutation was
determined respectively with polymerase chain reaction-restriction fragment
length polymorphism (PCR-RLFP), real time-amplification refractory mutation
system-quantitative PCR (RT-ARMS-qPCR) and pyrosquencing. Eleven plasmids with
various heteroplasmic levels of the 3243A->G mutation (ranging from 0 to
100%)were constructed as the standards. The reliability of above methods was
compared by correlation coefficient based on observed and expected values.
RESULTS: For all three methods, measurement of the standards showed a linear
correlation between the expected and detected values, i.e., PCR-RFLP
(R(2)=0.828), RT-ARMS-qPCR (R(2)=0.998) and pyrosquencing (R(2)=0.997). For the
MIDD family, it was consistent that there are 13 members carrying the A3243G
mutation with different heteroplasmic levels. And there was no significant
difference between the results by RT-ARMS-qPCR and pyrosquencing. CONCLUSION: PCR
RFLP is not appropriate for the quantitative detection but could be used for
early clinical screening. Both RT-ARMS-qPCR and pyrosquencing are suitable for
the detection of low heteroplasmic level of A3243G mutation. Compared with
pyrosquencing, RT-ARMS-qPCR is rapid, reliable and cost-effective, and is the
best choice for detecting low mutation loads.
PMID- 25119907
TI - [Genetic diagnosis and analysis of related genes for a pedigree with 2p25 and
12p13 cryptic rearrangements].
AB - OBJECTIVE: To analyze chromosome aberration in a child with mental retardation
and abnormalities and its parents. METHODS: Chromosome G banding, multiplex
ligation-dependent probe amplification, fluorescence in situ hybridization and
single nucleotide polymorphisms array were employed for analysis. RESULTS:
Karyotype analysis revealed that the child was 46,XX and the father was 46,XY,
while the mother was 46,XX, add (12)(p13). Subtelomeric region analysis with MLPA
displayed that the child has reduced ACP1 gene copy number in 2p25 region and
increased SLC6A12,KDM5A gene copy numbers in 12p11 region. SNP-array has fine
mapped the duplication to 12p13.33-p12.3, a 15.142 Mb region, and a deletion to
2p25.3 for 3.194 Mb, which resulted in duplication of 9 genes including SLC6A12
as well as deletion of 11 genes including SNTG2, respectively. FISH analysis
revealed that the child was 46,XX,ish,der(2),t(2;12)(p25;p13)mat, or partial
monosomy 2p25 and partial trisomy 12p13. In addition,the mother was a carrier
with cryptic balanced translocation chromosome, 46,XX,isht(2;12) (p25;p13).
Mental abnormalities and retardation of the child may be attributed to
heterozygous deletion of SNTG2, MYT1L genes and duplication of SLC6A12 gene.
CONCLUSION: Combined use of MLPA, FISH and SNP-array can facilitate accurate
diagnosis of cryptic rearrangement at genomic level.
PMID- 25119908
TI - [Association of CMA1 gene tag single nucleotide polymorphisms with essential
hypertension in Yi population from Yunnan].
AB - OBJECTIVE: To assess the association of tag single nucleotide polymorphisms (tag
SNPs) of chymase gene (CMA1) with essential hypertension in Yi population from
Yunnan, China. METHODS: A case-control study was carried out. Four tag
SNPs(rs1956921, rs1800876, rs5244 and rs1885108) were genotyped in 303 patients
with essential hypertension and 312 healthy controls using polymerase chain
reaction - restriction fragment length polymorphism(PCR-RFLP) method. RESULTS: No
significant difference in genotypic and allelic distributions of the four
polymorphisms was detected between the two groups(P>0.05), and the same results
existed in the females. The frequencies of rs1956921 C allele and a C-T haplotype
constructed with rs1956921 and rs5244 were greater in male patients compared with
male controls(P<0.01). CONCLUSION: The rs1956921 C allele of the CMA1 gene and
the C-T haplotype constructed with rs1956921 and rs5244 may be risk factors for
essential hypertension in ethnic Yi males from Yunnan.
PMID- 25119909
TI - [Association of TLR4 gene polymorphisms with large artery atherosclerotic stroke
and vascular bed selectivity of atherosclerotic lesions].
AB - OBJECTIVE: To assess the association of TLR4 gene polymorphisms with large artery
atherosclerosis (LAA) stroke and liability to atherosclerosis in an ethnic Han
population from northern China. METHODS: The study has involved 286 LAA stroke
patients and 300 healthy controls. The LAA group has been divided 4 subsets
according to angiostenosis conditions. Polymerase chain reaction-restriction
fragment length polymorphism and pyrosequencing were employed to analyze three
single nucleotide polymorphism (SNPs) (rs1927914, rs1927911 and rs2149356) of the
TLR4 gene. A Haploview software package was used to analyze the haplotypes.
RESULTS: SNPs rs1927911 and rs2149356 were associated with LAA stroke. Genotypic
and allelic frequencies of rs1927914 did not differ significantly between the two
groups. Genetic variants of the three SNPs did not vary significantly between all
subsets. Haplotype analysis was revealed a significant difference between the LAA
group and the control group. Compared with the controls, the frequencies of
haplotypes H2 and H8 were lower, and that of H3 was greater in the LAA group.
CONCLUSION: An association between the TLR4 gene polymorphisms and LAA stroke
subtype in ethnic Han population in northern China has been found. However, no
association of liability to atherosclerosis in different vascular bed has been
found with these polymorphisms.
PMID- 25119910
TI - [Influence of assisted reproduction technologies on genomic imprinting of embryos
and offspring].
AB - Assisted reproduction technologies (ART) include controlled ovarian
hyperstimulation, in vitro fertilization-embryo transfer, intracytoplasmic sperm
injection, in vitro maturation of oocytes, pre-implantation genetic diagnosis,
etc. They have been used for the treatment of impaired fertility but may damage
the health of offspring. The ART procedures may alter the epigenetic status of
these offspring and DNA methylation may be a crucial mechanism. This paper
summarizes epigenetic alterations in ART embryos and offspring, and discusses the
risks.
PMID- 25119911
TI - [The function of transcription factor P63 and its signaling pathway during limb
development].
AB - The development of human limb is controlled by several transcription factors and
signaling pathways, which are organized in precise time- and space-restricted
manners. Recent studies showed that P63 and its signaling pathway play important
roles in this process. Transcription factor P63, one member of the P53 family, is
characterized by a similar amino acid domain, plays a crucial role in the
development of limb and ectoderm differentiation, especially with its DNA binding
domain, and sterile alpha motif domains. Mutated P63 gene may produce abnormal
transcription factor P63 which can affect the signaling pathway. Furthermore,
defective signaling protein in structure and/or quantity is synthesized though
the pathway. Eventually, members of the signaling protein family are involved in
the regulation of differentiation and development of stem cell, which causes
deformity of limbs. In brief, three signaling pathways are related to the digit
formation along three axes, including SHH-ZPA, FGFs-AER and Lmx1B-Wnt7a-En1. Each
contains numerous signaling molecules which are integrated in self-regulatory
modules that assure the acquisition or the correct digit complements. These
finding has brought new clues for deciphering the etiology of congenital limb
malformation and may provide alternatives for both prevention and treatment.
PMID- 25119912
TI - [Detection of mosaic trisomy 9 missed by conventional cytogenetics using SNP
array and fluorescence in situ hybridization].
AB - OBJECTIVE: To detect mosaic trisomy 9 missed by conventional cytogenetics.
METHODS: Peripheral blood genomic DNA from a girl with mental retardation was
analyzed using Affymetrix CytoScan (TM) HD array. Fluorescence in situ
hybridization (FISH) was also performed on samples from two patients. RESULTS:
The SNP-array analysis has revealed multiple duplications along chromosome 9.
FISH analysis showed that, for the peripheral blood sample from one patient, 40
of 100 interphase cells and 15 of 100 metaphase cells carried trisomy 9. For the
cord blood sample from another patient, 35 of 100 interphase cells and 10 of 100
cultured cells carried trisomy 9. CONCLUSION: SNP-array is useful for detecting
low-level mosaicism which may be missed by conventional cytogenetics. Combined
with karyotype and microarray analyses, FISH is a focused and targeted approach
for diagnosing mosaic trisomy. They may provide a useful tool for differentiating
pseudomosaicisms from true mosaicisms.
PMID- 25119913
TI - [Identification of a novel splicing mutation in COL1A1 gene in a Chinese family
affected with typeIosteogenesis imperfecta].
AB - OBJECTIVE: To investigate the genetic cause for a large family affected with
typeIosteogenesis imperfecta. METHODS: Genomic DNA was extracted from peripheral
venous blood samples. The entire coding region and intron-exon boundaries of the
COL1A1 gene were subjected to PCR amplification and direct sequencing. Total RNA
was also extracted from immortalized B cell lines from the patients, with the
first strand of cDNA synthesized with an oligo(dT)18 primer. The PCR products
were directly sequenced using the TA cloned plasmid. RESULTS: A c.3208G>A
mutation has been identified in the COL1A1 gene, which can alter the splicing
pattern of mRNA. CONCLUSION: A novel splicing mutation c.3208G>A of the COL1A1
gene probably underlies the disease.
PMID- 25119915
TI - [Establishment of an allele-specific PCR method for direct screening of CYP21A2
gene mutation].
AB - OBJECTIVE: To establish an allele-specific PCR method for detect screening of
CYP21A2 gene mutation. METHODS: Allele-specific PCR primers and analogy primers
were designed based on the sequence alignment of CYP21A2 and CYP21AP genes.
Genomic DNA was extracted from blood specimens of 4 patients with 21-hydroxylase
deficiency and 5 healthy controls and respectively amplified with allele-specific
PCR primers and analogy primers and sequenced. RESULTS: Mutations of CYP21A2
including IVS2-13A/C>G, Arg356Trp and Arg149Pro were found with the established
method in all of the 4 patients but not in the healthy controls. When detected
with the analogy primers set, IVS2-13A/C>G and Arg356Trp were observed in both
patients and healthy controls. CONCLUSION: The allele-specific PCR-based method
is a simple, effective and reliable method for the detection of CYP21A2 gene
mutation.
PMID- 25119914
TI - [Limb-girdle muscular dystrophy type 2G: clinical, pathological and genetic
analysis of a case].
AB - OBJECTIVE: To investigate TCAP gene mutation and clinical features of a Chinese
patient with limb-girdle muscular dystrophy type 2G(LGMD 2G). METHODS: Clinical
data of the patient was analyzed. Exons of the TCAP gene were amplified and
sequenced. RESULTS: The patient has presented clinically as LGMD and
pathologically as vacuolar myopathy. Genetic analysis has identified compound
heterozygous mutations of exons 1 and 2 of the TCAP gene(c.100delC, c.166insG).
CONCLUSION: LGMD is a group of neuromuscular disorders with substantial
phenotypic heterogeneity. Genetic diagnosis has become indispensable for accurate
diagnosis for patients suspected to have the disease.
PMID- 25119916
TI - [Result survey analysis of prenatal chromosome karyotyping in an external quality
assessment program].
AB - OBJECTIVE: To analyze the results of prenatal karyotype of the external quality
assessment program in 2013 in order to provide references and recommendations for
improving the capability and performances of karyotype analysis of prenatal
screening laboratories. METHODS: Five lots of quality control cell photos were
sent to 500 laboratories. The participants were asked to decide whether the
photos have demonstrated any abnormal karyotype and determine the abnormal type.
The results should be submitted before the deadline and compared with the
standard results to evaluate the performances of the laboratory. RESULTS: One
hundred forty three laboratories have returned their karyotype results for the
survey. The standard answers were 7,XX,+18, 46,X,i(X)(q10), 46,XY,i(21)(q10) or
46,XY,+21,der(21;21)(q10;q10), 46,XY and 47,XY,+21 in sequential order, which
were used to estimate the score of each participant. The pass rates for five lots
were 97.9%, 97.2%, 95.8%, 100.0% and 97.9%, respectively. The total pass rate was
97.7%. The error rates were 2.1%, 2.8%, 4.2%, 0 and 2.1%, respectively. The total
error rate was 2.3%. CONCLUSION: Some laboratories did not correctly identify the
abnormal karyotypes, while some could not determine the right type of karyotype.
The external quality assessment program of prenatal diagnosis of karyotype
analysis should be conducted annually in order to improve the capability and
performances of karyotype analysis of prenatal screening laboratories.
PMID- 25119917
TI - [Analysis of erythroid-specific blood group genes using un-mobilized peripheral
stem cells cultured in vitro].
AB - OBJECTIVE: To analyze specific expression of blood group genes using nucleated
erythroid cells cultured from un-mobilized peripheral stem cells in vitro.
METHODS: Hematopoietic stem cells(HSC) bearing the CD34 antigen were isolated
from peripheral blood by centrifugation and magnetic beads sorting, followed by
suspension culture in vitro. Cells were collected from medium on various stages
and analyzed by immunofluorescence. The RNA transcription of RH and ABO blood
group genes was analyzed using culture cells on day 12. RESULTS: A total
of(3.19+/-0.13) *10 (4) CD34+cells were isolated from about 50 mL peripheral
blood with a recovery rate of 67.3%+/-2.7%. The cells amount in erythroid-lineage
culture system on day 9 reached a plateau of a 237.1+/-15.5-fold amplification of
the initial cell input. The stem cell-specific CD34 antigen was dropped off,
while the erythroid-specific CD235a and CD240D antigens were increased in culture
period. RHD/CE and ABO genes can be amplified using RNA extracted from culture
cells on day 12, and genotypes of Rh and ABO systems by DNA sequencing were
consistent with their serologic phenotypes. CONCLUSION: A method was established
to analyze the gene expression of erythroid blood group derived from un-mobilized
peripheral stem cells cultured in vitro. It can be used to study the expression
of various erythroid-specific genes.
PMID- 25119918
TI - [Association of MMP-14 gene polymorphism with cerebral infarction - a case
control study].
AB - OBJECTIVE: To investigate the association between cerebral infarction (CI) and
single nucleotide polymorphism (SNP) in the exon of membrane-type 1 matrix
metalloproteinase (MMP-14) gene in Chinese Han population. METHODS: Five hundred
seventy four patients with CI and 463 healthy individuals were recruited. Serum
MMP-14 level was measured with enzyme-linked immunosorbent assay (ELISA).
rs1042704 and rs2236307 polymorphisms of the MMP-14 gene were genotyped with a
TaqMan assay. Multivariate logistic regression was carried out to analyze the
risk factors of CI. RESULTS: A significant lower risk of CI was found in
individuals with MMP-14 rs2236307 TC and CC genotypes (vs. TT genotype: P<0.05).
The frequencies of MMP-14 rs2236307 C allele were significantly different between
the CI group (37.46%) and the control group (43.95%) (P=0.003). Serum level of
MMP-14 was higher in the CI group (P=0.003) and was also higher in the group with
MMP-14 rs2236307 TT genotype compared with those with CT and CC genotypes
(P=0.000; P=0.009). Logistic regression analysis indicated that the MMP-14
rs2236307 CT+CC genotypes was a protective factor, and that history of
hypertension, smoking status, triglycerides, diastolic blood pressure and
systolic blood pressure were the independent risk factors of CI (AOR:2.027,
1.302, 1.296, 1.434, 2.087; P<0.05). CONCLUSION: The rs2236307 polymorphism of
MMP-14 gene is associated with CI, for which the C allele maybe a protective
factor. No association of MMP-14 gene rs1042704 polymorphism with CI has been
found.
PMID- 25119919
TI - [Analysis for 2 samples with HLA-DQB1 allele dropout at exon 2 in sequence-based
typing].
AB - OBJECTIVE: To explore the reason for HLA-DQB1 allele dropout during routine
sequence-based typing(SBT) in order to improve the accuracy of typing. METHODS:
Two thousand samples derived from HLA high-resolution typing laboratory were
typed for HLA-DQB1 locus using an AlleleSEQR HLA-DQB1 SBT kit. Non-conclusive
results and "abnormal" sequencing samples were retyped using a LABType rSSO HD
HLA-DQB1 kit and further analyzed with both sequence-specific primers and group
specific primers and sequenced for haplotype analysis. RESULTS: Among the 2000
samples, 2 samples with no conclusive result were identified. The heterozygosity
was confirmed with both the LAB Type SSO HD HLA-DQB1 kit and PCR-SBT in house
method. Subsequent HLA-DQB1 cloning and haplotype sequencing have elucidated that
HLA-DQB1*02:02 dropped out at exon 2 for the first sample and HLA-DQB1*02:01:01
dropped out at exon 2 for the second sample during PCR amplification. No novel
nucleotide mutation was found. CONCLUSION: Our results indicated that
preferential amplification at exon 2 of DQB1 may result in allele dropout in exon
2 sequences during HLA-DQB1 SBT test. This may provide useful information for HLA
genotyping.
PMID- 25119921
TI - [Spinocerebellar ataxia-a family with eight cases].
PMID- 25119920
TI - [Detection of p53 gene deletion in Xinjiang patients with chronic lymphocytic
leukemia by fluorescence in situ hybridization and its clinical significance].
AB - OBJECTIVE: To investigate the presence of p53 gene deletion in Xinjiang patients
with chronic lymphocytic leukemia and its clinical significance. METHODS:
Interphase fluorescence in situ hybridization (FISH) was used to detect the p53
gene deletion in 77 patients with CLL. Presence of the deletion and its
association with clinical and laboratory features as well as prognostic factors
were analyzed. Kaplan-Meier method was used to calculate survivals, and the
results were compared using a Log-rank test. RESULTS: p53 gene deletion was found
in 10 (12.9%) of the patients but none from the control group (P<0.05). The
deletion was found in 12.5% (4/32) of ethnic Hans and 13.3% (6/45) of ethnic
Uyghurs (P>0.05). No significant different distribution of p53 gene deletion was
found in regard to sex, age, ethnicity, peripheral blood cell count (except for
Hb) or the levels of lactate dehydrogenase, beta2-micro globulin and CD38
(P>0.05). The deletion rate was higher in the group with high expression of ZAP
70 and patients with advanced stage disease than that in the group of low
expression and early-stage CLL (P<0.05). Among 20 patients who received
fludarabine therapy, the overall remission rate for those with p53 gene deletion
(20%) was lower than those without (75%) (P<0.05). With a median follow-up time
of 39.0 (8.0-136.0) months, 11 cases had died (14.3%), among them, 7 cases died
from CLL and related complications, and all of them were founded p53 gene
deletion. In patients with p53 gene deletion, the progression-free survival (18
months) was shorter than those without the deletion (55 months) (P<0.05).
CONCLUSION: The p53 gene deletion has been found in more than 10% of patients
with CLL, and the deletion rate did not significantly differ between ethnic Han
and Uyghur patients. The deletion is associated with advanced stage of the
disease. High-level ZAP-70 expression and the presence of p53 deletion are
associated with shorter survival and poor response to fludarabine containing
therapy. Therefore, drugs affecting the p53 signaling pathway should be avoided.
PMID- 25119922
TI - [Association of polymorphisms of HLA-DRB1 gene with unexplained recurrent
spontaneous abortion in ethnic Hans from Henan].
AB - OBJECTIVE: To assess the association of polymorphisms of human leukocyte antigen
DRB1 gene (HLA-DRB1) with susceptibility to unexplained recurrent spontaneous
abortion (URSA). METHODS: The HLA-DRB1 gene was typed with polymerase chain
reaction-specific sequence primers (PCR-SSP) method in 200 couples with URSA and
200 couples with a normal pregnancy history. RESULTS: The frequencies of DRB1*09
and DRB1*13 alleles were significantly greater in the URSA group compared with
the control group (14.50% vs. 9.50%, and 7.00% vs. 4.38%, both P<0.05), whilst
the frequencies of DRB1*04 and DRB1*12 alleles were significantly lower (7.13%
vs. 10.75%, and 8.63% vs. 14.38%, both P<0.05). For females from the URSA group,
the frequency of DRB1*09 allele (14.00%) was significantly higher compared with
the controls (9.25%) (P=0.036), whilst the frequency of DRB1*12(8.50%) allele was
significantly lower (14.00%) (P=0.014). For males in the URSA group, the
frequencies of DRB1*09 and DRB1*13 alleles were significantly higher than those
of the controls (15.00% vs. 9.75%, and 9.25% vs. 4.00%, both P<0.05), whilst the
frequencies of DRB1*04 and DRB1*12 alleles were significantly lower (5.75% vs.
12.25%, and 8.75% vs. 14.75%, P<0.05). CONCLUSION: The DRB1*09 and DRB1*13
alleles may contribute to the susceptibility of URSA, while DRB1*04 and DRB1*12
alleles may confer a protective effect factors. For females, however, no
significant association of DRB1*13 and DRB1*04 alleles with URSA was found.
PMID- 25119923
TI - [Clinical and genetics characteristics of patients with monosomal karyotype acute
myeloid leukemia patients].
AB - OBJECTIVE: To investigate the clinical and genetics characteristics of patients
with monosomal karyotype acute myeloid leukemia (MK-AML). METHODS: The karyotypes
of 3743 patients with newly-diagnosed de novo AML were analyzed, which had
identified 153 cases with MK-AML, for whom the clinical and genetics
characteristics were analyzed. RESULTS: There were 2056 patients (54.9%) among
all patients. A total of 153 patients fulfilling the criteria for MK-AML were
identified, which comprised 93 males and 60 females, with a median age of 54. The
median white blood cell count on presentation was 4.4*10 (9)/L. One hundred and
forty-five cases (94.8%) have fulfilled the criteria for complex karyotype (>= 3
chromosomal abnormalities). Although the monosomy could be found with all
autosomes, chromosome 7 has been most frequently involved (38.56%, 59/153).
CONCLUSION: MK-AML is a distinct cytogenetic subtype of AML. Monosomy 7 is
frequently detected among MK-AML patients. The monosomal karyotype is common
among elder patients with AML.
PMID- 25119924
TI - [Sequence analysis of a novel allele HLA-C*01:78].
AB - OBJECTIVE: To investigate the genetic basis for a novel allele HLA-C*01:78.
METHODS: Genomic DNA was extracted from peripheral blood using a QIAGEN quick DNA
extraction kit. The regions encompassing HLA-C from exon 1 to intron 3 and intron
3 to 3'UTR were amplified and cloned using a cloning sequencing kit in order to
split the two alleles apart. Selected clones were sequenced to include exons 2 to
4. RESULTS: Sequencing results have indicated the HLA-C alleles of the proband to
be a novel C*03:04 allele. The sequence has been submitted to GenBank (KF049216).
BLAST analysis has confirmed the novel allele to have one nucleotide difference
as C*01:03 at genomic nt316C>A (codon 82CGC>AGC) in exon 2, which has resulted in
replacement of one amino acid (82R>S). CONCLUSION: The novel allele has been
officially named as C*01:78 by the WHO Nomenclature Committee. The HLA allele
type of the proband was therefore A*02:07, 24:02; B*40:01, 46:01; C*01:78, 03:04;
DQB1*05:02, 05:02; DRB1*16:02, 16:02.
PMID- 25119925
TI - [Identification of a novel allele HLA-B*37:04:02].
AB - OBJECTIVE: To report on a novel HLA allele identified in a Chinese individual.
METHODS: Routine HLA genotyping was carried out with polymerase chain reaction
sequence specific oligonucleotide probes (PCR-SSOP) and sequencing-based typing
(SBT). RESULTS: A new HLA allele has been identified. The sequence differed from
its closest allele B*37:04:01 at nt618 (GCG->GCA), which resulted in no change of
codon 206. CONCLUSION: A novel HLA allele HLA-B*37:04:02 (GU391034) has been
identified and officially named by the WHO Nomenclature Committee.
PMID- 25119927
TI - [Two pedigrees with benign adult familial myoclonic epilepsy].
PMID- 25119926
TI - [Confirmation of 17 rare HLA alleles and prediction of their haplotypes].
AB - OBJECTIVE: To confirm 17 rare HLA alleles detected during routine HLA typing and
deduce their haplotypes. METHODS: Bi-allelic sequence-based typing and Luminex
DNA PCR-SSOP assay were applied for the initial or repeat HLA typing,
respectively. The rare HLA alleles were confirmed with mono-allelic sequence
based typing. Predicted haplotypes of the rare alleles were inferred based on the
frequencies of HLA alleles and haplotypes in Han population. RESULTS: The
authenticity of the total 17 rare HLA alleles was proven, and 18 predicted
haplotypes associated with the rare alleles were recognized. A*11:12 and
DRB1*13:19 were detected twice among unrelated individuals. CONCLUSION: Study of
rare HLA alleles and predicted haplotype can provide useful information for donor
searching and transplantation, and enrich polymorphisms of HLA in this
population.
PMID- 25119928
TI - [Hereditary spinocerebellar ataxia-a pedigree with six cases].
PMID- 25119931
TI - Excited-state wavepacket and potential reconstruction by coherent anti-Stokes
Raman scattering.
AB - Among the major challenges in the chemical sciences is controlling chemical
reactions and deciphering their mechanisms. Since much of chemistry occurs in
excited electronic states, in the last three decades scientists have employed a
wide variety of experimental techniques and theoretical methods to recover
excited-state potential energy surfaces and the wavepackets that evolve on them.
These methods have been partially successful but generally do not provide a
complete reconstruction of either the excited state wavepacket or potential. We
have recently proposed a methodology for reconstructing excited-state molecular
wavepackets and the corresponding potential energy surface [Avisar and Tannor,
Phys. Rev. Lett., 2011, 106, 170405]. In our approach, the wavepacket is
represented as a superposition of the set of vibrational eigenfunctions of the
molecular ground-state Hamiltonian. We assume that the multidimensional ground
state potential surface is known, and therefore these vibrational eigenfunctions
are known as well. The time-dependent coefficients of the basis functions are
obtained by experimental measurement of the resonant coherent anti-Stokes Raman
scattering (CARS) signal. Our reconstruction strategy has several significant
advantages: (1) the methodology requires no a priori knowledge of any excited
state potential. (2) It applies to dissociative as well as to bound excited-state
potentials. (3) It is general for polyatomics. (4) The excited-state potential
surface is reconstructed simultaneously with the wavepacket. Apart from making a
general contribution to the field of excited-state spectroscopy, our method
provides the information on the excited-state wavepacket and potential necessary
to design laser pulse sequences to control photochemical reactions.
PMID- 25119929
TI - Novel secondary somatic mutations in Ewing's sarcoma and desmoplastic small round
cell tumors.
AB - BACKGROUND: Ewing's sarcoma (ES) and desmoplastic small round cell tumors (DSRCT)
are small round blue cell tumors driven by an N-terminal containing EWS
translocation. Very few somatic mutations have been reported in ES, and none have
been identified in DSRCT. The aim of this study is to explore potential
actionable mutations in ES and DSRCT. METHODOLOGY: Twenty eight patients with ES
or DSRCT had tumor tissue available that could be analyzed by one of the
following methods: 1) Next-generation exome sequencing platform; 2) Multiplex
PCR/Mass Spectroscopy; 3) Polymerase chain reaction (PCR)-based single- gene
mutation screening; 4) Sanger sequencing; 5) Morphoproteomics. PRINCIPAL
FINDINGS: Novel somatic mutations were identified in four out of 18 patients with
advanced ES and two of 10 patients with advanced DSRCT (six out of 28
(21.4%));KRAS (n = 1), PTPRD (n = 1), GRB10 (n = 2), MET (n = 2) and PIK3CA (n =
1). One patient with both PTPRD and GRB10 mutations and one with a GRB10 mutation
achieved a complete remission (CR) on an Insulin like growth factor 1 receptor
(IGF1R) inhibitor based treatment. One patient, who achieved a partial remission
(PR) with IGF1R inhibitor treatment, but later developed resistance, demonstrated
a KRAS mutation in the post-treatment resistant tumor, but not in the pre
treatment tumor suggesting that the RAF/RAS/MEK pathway was activated with
progression. CONCLUSIONS: We have reported several different mutations in
advanced ES and DSRCT that have direct implications for molecularly-directed
targeted therapy. Our technology agnostic approach provides an initial mutational
roadmap used in the path towards individualized combination therapy.
PMID- 25119930
TI - Final results of a phase II study of paclitaxel, bevacizumab, and gemcitabine as
first-line therapy for patients with HER2-negative metastatic breast cancer.
AB - BACKGROUND: Efficacy and safety data for combining bevacizumab, gemcitabine, and
paclitaxel for locally advanced/metastatic breast cancer are limited. PATIENTS
AND METHODS: AVALUZ trial evaluates the combination of bevacizumab 10 mg/kg,
gemcitabine 2,000 mg/m(2) plus paclitaxel 150 mg/m(2), on days 1 and 15 of each
28-day course in previously untreated HER-2 negative patients. RESULTS: Median
progression-free survival (PES): 12.3 months. The overall response and clinical
benefit rate (CR + PR + SD) were 72 % (95 % CI 60.9-82.0 %) and 89 % (95 % CI
80.3-95.3 %), respectively. Median overall survival: 27.4 mo. Baseline
circulating tumor cell (CTCs) >=2 versus CTCs <2 was associated with lower PFS, p
= 0.046. Overall response was significantly greater in patients with intense
angiotensin type 1 receptor (AGTR1) expression (99 vs. 60 % [p = 0.021]). The
most frequent grade 3/4 adverse events were: neutropenia (10 %); febrile
neutropenia (1 %); sensory neuropathy (13 %); and asthenia (6 %). Grade 3 adverse
events of interest with bevacizumab included bleeding (1 %) and hypertension (4
%). One patient developed cardiac ischemia (1 %). CONCLUSIONS: Adding bevacizumab
to chemotherapy appeared feasible and well tolerated, producing toxicity
comparable to other effective combined first-line regimens. Baseline circulating
endothelial cells and AGTR1 expression are predictive of PFS and response.
PMID- 25119932
TI - Screening for depressive symptoms in older adults in the Family Health Strategy,
Porto Alegre, Brazil.
AB - OBJECTIVE To analyze the prevalence of depression in older adults and associated
factors. METHODS Cross-sectional study using a stratified random sample of 621
individuals aged >= 60 from 27 family health teams in Porto Alegre, RS, Southern
Brazil, between 2010 and 2012. Community health agents measured depression using
the 15-item Geriatric Depression Scale. Scores of >= 6 were considered as
depression and between 11 and 15 as severe depression. Poisson regression was
used to search for independent associations of sociodemographic and self
perceived health with both depression and its severity. RESULTS The prevalence of
depression was 30.6% and was significantly higher in women (35.9% women versus
20.9% men, p < 0.001). The variables independently associated with depression
were: female gender (PR = 1.4, 95%CI 1.1;1.8); low education, especially
illiteracy (PR = 1.8, 95%CI 1.2;2 6); regular self-rated health (OR = 2.2, 95%CI
1.6;3.0); and poor/very poor self-rated health (PR = 4.0, 95%CI 2.9;5.5). Except
for education, the strength of association of these factors increases
significantly in severe depression. CONCLUSIONS A high prevalence of depression
was observed in the evaluations conducted by community health agents,
professionals who are not highly specialized. The findings identified using the
15-item Geriatric Depression Scale in this way are similar to those in the
literature, with depression more associated with low education, female gender and
worse self-rated health. From a primary health care strategic point of view, the
findings become still more relevant, indicating that community health agents
could play an important role in identifying depression in older adults.
PMID- 25119933
TI - Disability in instrumental activities of daily living among older adults: gender
differences.
AB - OBJECTIVE To analyze gender differences in the incidence and determinants of
disability regarding instrumental activities of daily living among older adults.
METHODS The data were extracted from the Saude, Bem-Estar e Envelhecimento (SABE
Health, Wellbeing and Ageing) study. In 2000, 1,034 older adults without
difficulty in regarding instrumental activities of daily living were selected.
The following characteristics were evaluated at the baseline: sociodemographic
and behavioral variables, health status, falls, fractures, hospitalizations,
depressive symptoms, cognition, strength, mobility, balance and perception of
vision and hearing. Instrumental activities of daily living such as shopping and
managing own money and medication, using transportation and using the telephone
were reassessed in 2006, with incident cases of disability considered as the
outcome. RESULTS The incidence density of disability in instrumental activities
of daily living was 44.7/1,000 person/years for women and 25.2/1,000 person/years
for men. The incidence rate ratio between women and men was 1.77 (95%CI
1.75;1.80). After controlling for socioeconomic status and clinical conditions,
the incidence rate ratio was 1.81 (95%CI 1.77;1.84), demonstrating that women
with chronic disease and greater social vulnerability have a greater incidence
density of disability in instrumental activities of daily living. The following
were determinants of the incidence of disability: age >= 80 and worse perception
of hearing in both genders; stroke in men; and being aged 70 to 79 in women.
Better cognitive performance was a protective factor in both genders and better
balance was a protective factor in women. CONCLUSIONS The higher incidence
density of disability in older women remained even after controlling for adverse
social and clinical conditions. In addition to age, poorer cognitive performance
and conditions that adversely affect communication disable both genders. Acute
events, such as a stroke, disables elderly men more, whereas early deficits
regarding balance disable women more.
PMID- 25119934
TI - Cut-off point for WHOQOL-bref as a measure of quality of life of older adults.
AB - OBJECTIVE To propose a cut-off for the World Health Organization Quality of Life
Bref (WHOQOL-bref) as a predictor of quality of life in older adults.METHODS
Cross-sectional study with 391 older adults registered in the Northwest Health
District in Belo Horizonte, MG, Southeastern Brazil, between October 8, 2010 and
May 23, 2011. The older adults' quality of life was measured using the WHOQOL
bref. The analysis was rationalized by outlining two extreme and simultaneous
groups according to perceived quality of life and satisfaction with health
(quality of life good/satisfactory - good or very good self-reported quality of
life and being satisfied or very satisfied with health - G5; and poor/very poor
quality of life - poor or very poor self-reported quality of life and feeling
dissatisfied or very dissatisfied with health - G6). A Receiver-Operating
Characteristic curve (ROC) was created to assess the diagnostic ability of
different cut-off points of the WHOQOL-bref.RESULTS ROC curve analysis indicated
a critical value 60 as the optimal cut-off point for assessing perceived quality
of life and satisfaction with health. The area under the curve was 0.758, with a
sensitivity of 76.8% and specificity of 63.8% for a cut-off of >= 60 for overall
quality of life (G5) and sensitivity 95.0% and specificity of 54.4% for a cut-off
of < 60 for overall quality of life (G6).CONCLUSIONS Diagnostic interpretation of
the ROC curve revealed that cut-off < 60 for overall quality of life obtained
excellent sensitivity and negative predictive value for tracking older adults
with probable worse quality of life and dissatisfied with health.
PMID- 25119935
TI - Social protection systems in vulnerable families: their importance for the public
health.
AB - OBJECTIVE To analyze the effectiveness of the Chilean System of Childhood Welfare
in transferring benefits to socially vulnerable families. METHODS A cross
sectional study with a sample of 132 families from the Metropolitan Region,
Chile, stratified according to degree of social vulnerability, between September
2011 and January 2012. Semi-structured interviews were conducted with mothers of
the studied families in public health facilities or their households. The
variables studied were family structure, psychosocial risk in the family context
and integrated benefits from the welfare system in families that fulfill the
necessary requirements for transfer of benefits. Descriptive statistics to
measure location and dispersion were calculated. A binary logistic regression,
which accounts for the sample size of the study, was carried out. RESULTS The
groups were homogenous regarding family size, the presence of biological father
in the household, the number of relatives living in the same dwelling, income
generation capacity and the rate of dependency and psychosocial risk (p >= 0.05).
The transfer of benefits was low in all three groups of the sample (<= 23.0%).
The benefit with the best coverage in the system was the Single Family Subsidy,
whose transfer was associated with the size of the family, the presence of
relatives in the dwelling, the absence of the father in the household, a high
rate of dependency and a high income generation capacity (p <= 0.10). CONCLUSIONS
The effectiveness of benefit transfer was poor, especially in families that were
extremely socially vulnerable. Further explanatory studies of benefit transfers
to the vulnerable population, of differing intensity and duration, are required
in order to reduce health disparities and inequalities.
PMID- 25119936
TI - Perceived health in the Portuguese population aged >= 35.
AB - OBJECTIVE: To evaluate the exploratory relationship between determinants of
health, life satisfaction, locus of control, attitudes and behaviors and health
related quality of life in an adult population. METHODS: Observational study
(analytical and cross-sectional) with a quantitative methodological basis. The
sample was composed oy 1,214 inhabitants aged >= 35 in 31 civil parishes in the
County of Coimbra, Portugal, 2011-2012. An anonymous and voluntary health survey
was conducted, which collected the following information: demographic, clinical
record, health and lifestyle behaviors; health related quality of life (Medical
Outcomes Study, Short Form-36); health locus of control; survey of health
attitudes and behavior, and quality of life index. Pearson's Linear Correlation,
t-Student, Wilcoxon-Mann-Whitney; One-way ANOVA; Brown-Forsythe's F; Kruskal
Wallis; Multiple Comparisons: Tukey (HSD), Games-Howell and Conover were used in
the statistical analysis. RESULTS: Health related quality of life was shown to be
lower in females, in older age groups, in obese/overweight individuals, widows,
unassisted, those living alone, living in rural/suburban areas, those who did not
work and with a medium-low socioeconomic level. Respondents with poor/very poor
self-perceived health (p < 0.0001), with chronic disease (p < 0.0001), who
consumed < 3 meals per day (p <= 0.01), who were sedentary, who slept <= 6 h/day
and had smoked for several years revealed the worst health results. Health
related quality of life was positively related with a bigger internal locus, with
better health attitudes and behaviors (physical exercise, health and nutritional
care, length of dependence) and with different areas of life satisfaction.
CONCLUSIONS: Better health related quality of life was associated with certain
social, psychological, family and health characteristics, a satisfactory
lifestyle, better socioeconomic conditions and a good internal locus of control
over health attitudes and behaviors.
PMID- 25119937
TI - HIV risk practices by female sex workers according to workplace.
AB - OBJECTIVE To investigate differences in HIV infection- related risk practices by
Female Sex Workers according to workplace and the effects of homophily on
estimating HIV prevalence. METHODS Data from 2,523 women, recruited using
Respondent-Driven Sampling, were used for the study carried out in 10 Brazilian
cities in 2008-2009. The study included female sex workers aged 18 and over. The
questionnaire was completed by the subjects and included questions on
characteristics of professional activity, sexual practices, use of drugs, HIV
testing, and access to health services. HIV quick tests were conducted. The
participants were classified in two groups according to place of work: on the
street or indoor venues, like nightclubs and saunas. To compare variable
distributions by place of work, we used Chi-square homogeneity tests, taking into
consideration unequal selection probabilities as well as the structure of
dependence between observations. We tested the effect of homophily by workplace
on estimated HIV prevalence. RESULTS The highest HIV risk practices were
associated with: working on the streets, lower socioeconomic status, low regular
smear test coverage, higher levels of crack use and higher levels of syphilis
serological scars as well as higher prevalence of HIV infection. The effect of
homophily was higher among sex workers in indoor venues. However, it did not
affect the estimated prevalence of HIV, even after using a post-stratification by
workplace procedure. CONCLUSIONS The findings suggest that strategies should
focus on extending access to, and utilization of, health services. Prevention
policies should be specifically aimed at street workers. Regarding the
application of Respondent-Driven Sampling, the sample should be sufficient to
estimate transition probabilities, as the network develops more quickly among sex
workers in indoor venues.
PMID- 25119938
TI - Senses of body image in adolescents in elementary school.
AB - OBJECTIVE: To comprehend the perception of body image in adolescence. METHODS: A
qualitative study was conducted with eight focus groups with 96 students of both
sexes attending four public elementary school institutions in the city of Rio de
Janeiro, Southeastern Brazil, in 2013. An interview guide with questions about
the adolescents' feelings in relation to: their bodies, standards of idealized
beauty, practice of physical exercise and sociocultural influences on self-image.
In the data analysis we sought to understand and interpret the meanings and
contradictions of narratives, understanding the subjects' context and reasons and
the internal logic of the group. RESULTS: Three thematic categories were
identified. The influence of media on body image showed the difficulty of
achieving the perfect body and is viewed with suspicion in face of standards of
beauty broadcast; the importance of a healthy body was observed as standards of
beauty and good looks were closely linked to good physical condition and result
from having a healthy body; the relationship between the standard of beauty and
prejudice, as people who are not considered attractive, having small physical
imperfections, are discriminated against and can be rejected or even excluded
from society. CONCLUSIONS: The standard of perfect body propagated by media
influences adolescents' self-image and, consequently, self-esteem and is
considered an unattainable goal, corresponding to a standard of beauty described
as artificial and unreal. However, it causes great suffering and discrimination
against those who do not feel they are attractive, which can lead to health
problems resulting from low self-esteem.
PMID- 25119939
TI - Cumulative mortality of Aedes aegypti larvae treated with compounds.
AB - OBJECTIVE To evaluate the larvicidal activity of Azadirachta indica, Melaleuca
alternifolia, carapa guianensis essential oils and fermented extract of Carica
papaya against Aedes aegypti (Linnaeus, 1762) (Diptera: Culicidae). METHODS The
larvicide test was performed in triplicate with 300 larvae for each experimental
group using the third larval stage, which were exposed for 24h. The groups were:
positive control with industrial larvicide (BTI) in concentrations of 0.37 ppm
(PC1) and 0.06 ppm (PC2); treated with compounds of essential oils and fermented
extract, 50.0% concentration (G1); treated with compounds of essential oils and
fermented extract, 25.0% concentration (G2); treated with compounds of essential
oils and fermented extract, 12.5% concentration (G3); and negative control group
using water (NC1) and using dimethyl (NC2). The larvae were monitored every 60
min using direct visualization. RESULTS No mortality occurred in experimental
groups NC1 and NC2 in the 24h exposure period, whereas there was 100% mortality
in the PC1 and PC2 groups compared to NC1 and NC2. Mortality rates of 65.0%,
50.0% and 78.0% were observed in the groups G1, G2 and G3 respectively, compared
with NC1 and NC2. CONCLUSIONS The association between three essential oils from
Azadirachta indica, Melaleuca alternifolia, Carapa guianensis and fermented
extract of Carica papaya was efficient at all concentrations. Therefore, it can
be used in Aedes aegypti Liverpool third larvae stage control programs.
PMID- 25119940
TI - Principal components and generalized linear modeling in the correlation between
hospital admissions and air pollution.
AB - OBJECTIVE To analyze the association between concentrations of air pollutants and
admissions for respiratory causes in children. METHODS Ecological time series
study. Daily figures for hospital admissions of children aged < 6, and daily
concentrations of air pollutants (PM10, SO2, NO2, O3 and CO) were analyzed in the
Regiao da Grande Vitoria, ES, Southeastern Brazil, from January 2005 to December
2010. For statistical analysis, two techniques were combined: Poisson regression
with generalized additive models and principal model component analysis. Those
analysis techniques complemented each other and provided more significant
estimates in the estimation of relative risk. The models were adjusted for
temporal trend, seasonality, day of the week, meteorological factors and
autocorrelation. In the final adjustment of the model, it was necessary to
include models of the Autoregressive Moving Average Models (p, q) type in the
residuals in order to eliminate the autocorrelation structures present in the
components. RESULTS For every 10:49 MUg/m3 increase (interquartile range) in
levels of the pollutant PM10 there was a 3.0% increase in the relative risk
estimated using the generalized additive model analysis of main components
seasonal autoregressive - while in the usual generalized additive model, the
estimate was 2.0%. CONCLUSIONS Compared to the usual generalized additive model,
in general, the proposed aspect of generalized additive model - principal
component analysis, showed better results in estimating relative risk and quality
of fit.
PMID- 25119941
TI - Disparities in cervical and breast cancer mortality in Brazil.
AB - OBJECTIVE To analyze cervical and breast cancer mortality in Brazil according to
socioeconomic and welfare indicators. METHODS Data on breast and cervical cancer
mortality covering a 30-year period (1980-2010) were analyzed. The data were
obtained from the National Mortality Database, population data from the Brazilian
Institute of Geography and Statistics database, and socioeconomic and welfare
information from the Institute of Applied Economic Research. Moving averages were
calculated, disaggregated by capital city and municipality. The annual percent
change in mortality rates was estimated by segmented linear regression using the
joinpoint method. Pearson's correlation coefficients were conducted between
average mortality rate at the end of the three-year period and selected
indicators in the state capital and each Brazilian state. RESULTS There was a
decline in cervical cancer mortality rates throughout the period studied, except
in municipalities outside of the capitals in the North and Northeast. There was a
decrease in breast cancer mortality in the capitals from the end of the 1990s
onwards. Favorable socioeconomic indicators were inversely correlated with
cervical cancer mortality. A strong direct correlation was found with favorable
indicators and an inverse correlation with fertility rate and breast cancer
mortality in inner cities. CONCLUSIONS There is an ongoing dynamic process of
increased risk of cervical and breast cancer and attenuation of mortality because
of increased, albeit unequal, access to and provision of screening, diagnosis and
treatment.
PMID- 25119942
TI - Spatial study of homicide rates in the state of Bahia, Brazil, 1996-2010.
AB - OBJECTIVE To analyze the spatial distribution of homicide mortality in the state
of Bahia, Northeastern Brazil. METHODS Ecological study of the 15 to 39-year old
male population in the state of Bahia in the period 1996-2010. Data from the
Mortality Information System, relating to homicide (X85-Y09) and population
estimates from the Brazilian Institute of Geography and Statistics were used. The
existence of spatial correlation, the presence of clusters and critical areas of
the event studied were analyzed using Moran's I Global and Local indices. RESULTS
A non-random spatial pattern was observed in the distribution of rates, as was
the presence of three clusters, the first in the north health district, the
second in the eastern region, and the third cluster included townships in the
south and the far south of Bahia. CONCLUSIONS The homicide mortality in the three
different critical areas requires further studies that consider the
socioeconomic, cultural and environmental characteristics in order to guide
specific preventive and interventionist practices.
PMID- 25119943
TI - Deported Mexican migrants: health status and access to care.
AB - OBJECTIVE To describe the health status and access to care of forced-return
Mexican migrants deported through the Mexico-United States border and to compare
it with the situation of voluntary-return migrants. METHODS Secondary data
analysis from the Survey on Migration in Mexico's Northern Border from 2012. This
is a continuous survey, designed to describe migration flows between Mexico and
the United States, with a mobile-population sampling design. We analyzed
indicators of health and access to care among deported migrants, and compare them
with voluntary-return migrants. Our analysis sample included 2,680 voluntary
return migrants, and 6,862 deportees. We employ an ordinal multiple logistic
regression model, to compare the adjusted odds of having worst self-reported
health between the studied groups. RESULTS As compared to voluntary-return
migrants, deportees were less likely to have medical insurance in the United
States (OR = 0.05; 95%CI 0.04;0.06). In the regression model a poorer self
perceived health was found to be associated with having been deported (OR = 1.71,
95%CI 1.52;1.92), as well as age (OR = 1.03, 95%CI 1.02;1.03) and years of
education (OR = 0.94 95%CI 0.93;0.95). CONCLUSIONS According to our results,
deportees had less access to care while in the United States, as compared with
voluntary-return migrants. Our results also showed an independent and
statistically significant association between deportation and having poorer self
perceived health. To promote the health and access to care of deported Mexican
migrants coming back from the United States, new health and social policies are
required.
PMID- 25119944
TI - Cross-cultural validity of the demand-control questionnaire: Swedish and
Brazilian workers.
AB - OBJECTIVE To evaluate the cross-cultural validity of the Demand-Control
Questionnaire, comparing the original Swedish questionnaire with the Brazilian
version. METHODS We compared data from 362 Swedish and 399 Brazilian health
workers. Confirmatory and exploratory factor analyses were performed to test
structural validity, using the robust weighted least squares mean and variance
adjusted (WLSMV) estimator. Construct validity, using hypotheses testing, was
evaluated through the inspection of the mean score distribution of the scale
dimensions according to sociodemographic and social support at work variables.
RESULTS The confirmatory and exploratory factor analyses supported the instrument
in three dimensions (for Swedish and Brazilians): psychological demands, skill
discretion and decision authority. The best-fit model was achieved by including
an error correlation between work fast and work intensely (psychological demands)
and removing the item repetitive work (skill discretion). Hypotheses testing
showed that workers with university degree had higher scores on skill discretion
and decision authority and those with high levels of Social Support at Work had
lower scores on psychological demands and higher scores on decision authority.
CONCLUSIONS The results supported the equivalent dimensional structures across
the two culturally different work contexts. Skill discretion and decision
authority formed two distinct dimensions and the item repetitive work should be
removed.
PMID- 25119945
TI - Tuberculosis Control Program and patient satisfaction, Rio de Janeiro, Brazil.
AB - OBJECTIVE To evaluate factors associated with users' satisfaction in the
Tuberculosis Control Program. METHODS A cross-sectional study of 295 patients
aged >= 18 years, with two or more outpatient visits in the Tuberculosis Control
Program, in five cities in the metropolitan region of Rio de Janeiro, RJ,
Southeastern Brazil, in 2010. Considering an estimated population of 4,345
patients, the sampling plan included 15 health care units participating in the
program, divided into two strata: units in Rio de Janeiro City, selected with
probability proportional to the monthly average number of outpatient visits, and
units in the other four cities. In the units, four temporal clusters of five
patients each were selected with equal probability, totaling 300 patients. A
questionnaire investigating the users' clinical and sociodemographic variables
and aspects of care and service in the program relevant to user satisfaction was
applied to the patients. Descriptive statistics about users and their
satisfaction with the program were obtained, and the effects of factors
associated with satisfaction were estimated. RESULTS Patients were predominantly
males (57.7%), with a mean age of 40.9 and with low level of schooling. The mean
treatment time was 4.1 months, mostly self-administered (70.4%). Additionally,
25.8% had previously been treated for tuberculosis. There was a high level of
satisfaction, especially regarding medication provision, and respect to patients
by the health professionals. Patients who were younger (<= 30), those on self
administered treatment, and with graduate level, showed less satisfaction.
Suggestions to improve the services include having more doctors (70.0%), and
offering exams in the same place of attendance (55.1%). CONCLUSIONS Patient
satisfaction with the Tuberculosis Control Program was generally high, although
lower among younger patients, those with university education and those on self
administered treatment. The study indicates the need for changes to structural
and organizational aspects of care, and provides practical support for its
improvement.
PMID- 25119946
TI - Temporal trends and spatial distribution of unsafe abortion in Brazil, 1996-2012.
AB - OBJECTIVE To analyze temporal trends and distribution patterns of unsafe abortion
in Brazil. METHODS Ecological study based on records of hospital admissions of
women due to abortion in Brazil between 1996 and 2012, obtained from the Hospital
Information System of the Ministry of Health. We estimated the number of unsafe
abortions stratified by place of residence, using indirect estimate techniques.
The following indicators were calculated: ratio of unsafe abortions/100 live
births and rate of unsafe abortion/1,000 women of childbearing age. We analyzed
temporal trends through polynomial regression and spatial distribution using
municipalities as the unit of analysis. RESULTS In the study period, a total of
4,007,327 hospital admissions due to abortions were recorded in Brazil. We
estimated a total of 16,905,911 unsafe abortions in the country, with an annual
mean of 994,465 abortions (mean unsafe abortion rate: 17.0 abortions/1,000 women
of childbearing age; ratio of unsafe abortions: 33.2/100 live births). Unsafe
abortion presented a declining trend at national level (R2: 94.0%, p < 0.001),
with unequal patterns between regions. There was a significant reduction of
unsafe abortion in the Northeast (R2: 93.0%, p < 0.001), Southeast (R2: 92.0%, p
< 0.001) and Central-West regions (R2: 64.0%, p < 0.001), whereas the North (R2:
39.0%, p = 0.030) presented an increase, and the South (R2: 22.0%, p = 0.340)
remained stable. Spatial analysis identified the presence of clusters of
municipalities with high values for unsafe abortion, located mainly in states of
the North, Northeast and Southeast Regions. CONCLUSIONS Unsafe abortion remains a
public health problem in Brazil, with marked regional differences, mainly
concentrated in the socioeconomically disadvantaged regions of the country.
Qualification of attention to women's health, especially to reproductive aspects
and attention to pre- and post-abortion processes, are necessary and urgent
strategies to be implemented in the country.
PMID- 25119948
TI - Interface between intellectual disability and mental health: hermeneutic review.
AB - A literature review was conducted aiming to understand the interface between the
Intellectual Disability and Mental Health fields and to contribute to mitigating
the path of institutionalizing individuals with intellectual deficiencies. The so
called dual diagnosis phenomenon remains underestimated in Brazil but is the
object of research and specific public policy internationally. This phenomenon
alerts us to the prevalence of mental health problems in those with intellectual
disabilities, limiting their social inclusion. The findings reinforce the
importance of this theme and indicate possible diagnostic invisibility of the
development of mental illness in those with intellectual disabilities in Brazil,
which may contribute to sustaining psychiatric institutionalization of this
population.
PMID- 25119949
TI - Phytotherapy in primary health care.
AB - OBJECTIVE To characterize the integration of phytotherapy in primary health care
in Brazil. METHODS Journal articles and theses and dissertations were searched
for in the following databases: SciELO, Lilacs, PubMed, Scopus, Web of Science
and Theses Portal Capes, between January 1988 and March 2013. We analyzed 53
original studies on actions, programs, acceptance and use of phytotherapy and
medicinal plants in the Brazilian Unified Health System. Bibliometric data,
characteristics of the actions/programs, places and subjects involved and type
and focus of the selected studies were analyzed. RESULTS Between 2003 and 2013,
there was an increase in publications in different areas of knowledge, compared
with the 1990-2002 period. The objectives and actions of programs involving the
integration of phytotherapy into primary health care varied: including other
treatment options, reduce costs, reviving traditional knowledge, preserving
biodiversity, promoting social development and stimulating inter-sectorial
actions. CONCLUSIONS Over the past 25 years, there was a small increase in
scientific production on actions/programs developed in primary care. Including
phytotherapy in primary care services encourages interaction between health care
users and professionals. It also contributes to the socialization of scientific
research and the development of a critical vision about the use of phytotherapy
and plant medicine, not only on the part of professionals but also of the
population.
PMID- 25119947
TI - Non-adherence to telemedicine interventions for drug users: systematic review.
AB - OBJECTIVE To estimate rates of non-adherence to telemedicine strategies aimed at
treating drug addiction. METHODS A systematic review was conducted of randomized
controlled trials investigating different telemedicine treatment methods for drug
addiction. The following databases were consulted between May 18, 2012 and June
21, 2012: PubMed, PsycINFO, SciELO, Wiley (The Cochrane Library), Embase,
Clinical trials and Google Scholar. The Grading of Recommendations Assessment,
Development and Evaluation was used to evaluate the quality of the studies. The
criteria evaluated were: appropriate sequence of data generation, allocation
concealment, blinding, description of losses and exclusions and analysis by
intention to treat. There were 274 studies selected, of which 20 were analyzed.
RESULTS Non-adherence rates varied between 15.0% and 70.0%. The interventions
evaluated were of at least three months duration and, although they all used
telemedicine as support, treatment methods differed. Regarding the quality of the
studies, the values also varied from very poor to high quality. High quality
studies showed better adherence rates, as did those using more than one technique
of intervention and a limited treatment time. Mono-user studies showed better
adherence rates than poly-user studies. CONCLUSIONS Rates of non-adherence to
treatment involving telemedicine on the part of users of psycho-active substances
differed considerably, depending on the country, the intervention method, follow
up time and substances used. Using more than one technique of intervention, short
duration of treatment and the type of substance used by patients appear to
facilitate adherence.
PMID- 25119951
TI - Knowing the previously unknown: identification of a methodological challenge for
pharmacoepidemiology.
PMID- 25119950
TI - Study of T helper (17) and T regulatory cells in psoriatic patients receiving
live attenuated varicella vaccine therapy in a randomized controlled trial.
AB - BACKGROUND: The use of live attenuated varicella vaccine (Varilrix((r))) as an
adjuvant treatment in severe cases of psoriasis has recently been postulated. Its
efficacy raised questions regarding its possible mechanisms of action. OBJECTIVE:
To compare the efficacy and safety of combining Varilrix((r)) and cyclosporine to
cyclosporine alone in the treatment of severe psoriasis. Furthermore, to study
the expression of T helper (Th)17 and T regulatory (Tregs) cells before and after
therapy. MATERIALS AND METHODS: This randomized controlled trial included 24
psoriatic patients, randomly divided into 2 groups (A and B). All patients
received cyclosporine at a daily dose of 2.5 mg/kg/day. In addition, group A
received 4 doses of Varilrix((r)) once/3 weeks, and group B received 4 doses of
subcutaneous saline. Skin biopsies were obtained from all patients before and
after therapy and from all controls for estimation of interleukin (IL)-17, IL-22
and Forkhead boxP3 (FoxP3) using RT-PCR. RESULTS: Group A patients showed a
significantly higher % of clinical improvement (P = 0.011), which occurred
earlier than group B. At baseline, levels of IL-17 and IL-22 were significantly
higher while the level of FoxP3 was significantly lower in patients (P<0.001)
compared to controls. After therapy, both groups showed significant reductions in
both IL-17 and IL-22 levels, and significant elevation in FoxP3 (P<0.001). This
change was significantly more evident in group A patients. CONCLUSION: Live
attenuated varicella vaccine could play a role in the treatment of psoriasis when
combined with low dose cyclosporine through accentuating the influence on the
Th17/Treg balance.
PMID- 25119952
TI - Causal inference using mixture models: a word of caution.
PMID- 25119953
TI - Comparative effectiveness of patient-centered strategies to improve FDA
medication guides.
AB - BACKGROUND: Med Guides are the only Food and Drug Administration-regulated source
of written patient information distributed with prescriptions drugs. Despite
their potential value, studies have found them to have limited utility.
OBJECTIVE: To evaluate the effectiveness of patient-centered strategies for the
design of Med Guides to improve comprehension. DESIGN: A cross-sectional,
randomized trial. SETTING: Two primary care clinics in Chicago, Illinois; one
based in a public university hospital and the other within a private academic
medical center. PATIENTS: A total of 1003 adults aged 18-85 years. INTERVENTION:
The format and layout of content from 3 typical Med Guides (by reading
difficulty, length, exposure) were modified several ways to promote information
accessibility. Working with patients, the 3 most preferred versions were
evaluated. The first used 2 columns to organize content (Column), a second
mimicked over-the-counter "Drug Facts" labeling (Drug Facts), and the third
followed health literacy best practices using a simple table format (Health
Literacy prototype). MEASURES: Tailored comprehension assessment of content from
3 representative Med Guides. RESULTS: Comprehension was significantly greater for
all 3 prototypes compared with the current standard (all P<0.001). The Health
Literacy prototype consistently demonstrated the highest comprehension scores,
and in multivariable analyses, outperformed both the Drug Facts [beta=-4.43, 95%
confidence interval (CI), -6.21 to -2.66] and Column (beta=-4.04, 95% CI, -5.82
to -2.26) prototypes. Both older age (older than 60 y: beta=-10.54, 95% CI,
15.12 to -5.96), low and marginal literacy skills were independently associated
with poorer comprehension (low: beta=-31.92, 95% CI, -35.72 to -28.12; marginal:
beta=-12.91, 95% CI, -16.01 to -9.82). CONCLUSIONS: The application of evidence
based practices to the redesign of Med Guides significantly improved patient
comprehension. Although some age and literacy disparities were reduced with the
Health Literacy format in particular, both older age and low literacy remained
independently associated with poorer comprehension. More aggressive strategies
will likely be needed to gain assurances that all patients are informed about
their prescribed medications. TRIAL REGISTRATION: Clinical Trials.Gov
#NCT01731405.
PMID- 25119954
TI - Elderly breast and colorectal cancer patients' clinical course: patient and
contextual influences.
AB - BACKGROUND: The social and medical environments that surround people are each
independently associated with their cancer course. The extent to which these
characteristics may together mediate patients' cancer care and outcomes is not
known. METHODS: Using multilevel methods and data, we studied elderly breast and
colorectal cancer patients (level I) within urban social (level II: ZIP code
tabulation area) and health care (level III: hospital service area) contexts. We
sought to determine (1) which, if any, observable social and medical contextual
attributes were associated with patient cancer outcomes after controlling for
observable patient attributes, and (2) the magnitude of residual variation in
patient cancer outcomes at each level. RESULTS: Numerous patient attributes and
social area attributes, including poverty, were associated with unfavorable
patient cancer outcomes across the full clinical cancer continuum for both
cancers. Health care area attributes were not associated with patient cancer
outcomes. After controlling for observable covariates at all 3 levels, there was
substantial residual variation in patient cancer outcomes at all levels.
CONCLUSIONS: After controlling for patient attributes known to confer risk of
poor cancer outcomes, we find that neighborhood socioeconomic disadvantage exerts
an independent and deleterious effect on residents' cancer outcomes, but the area
supply of the specific types of health care studied do not. Multilevel
interventions targeted at cancer patients and their social areas may be useful.
We also show substantial residual variation in patient outcomes across social and
health care areas, a finding potentially relevant to traditional small area
variation research methods.
PMID- 25119955
TI - Prescription opioid use among disabled Medicare beneficiaries: intensity, trends,
and regional variation.
AB - BACKGROUND: Prescription opioid use and overdose deaths are increasing in the
United States. Among disabled Medicare beneficiaries under the age of 65, the
rise in musculoskeletal conditions as qualifying diagnoses suggests that opioid
analgesic use may be common and increasing, raising safety concerns. METHODS:
From a 40% random-sample Medicare denominator, we identified fee-for-service
beneficiaries under the age of 65 and created annual enrollment cohorts from 2007
to 2011 (6.4 million person-years). We obtained adjusted, annual opioid use
measures: any use, chronic use (>= 6 prescriptions), intensity of use [daily
morphine equivalent dose (MED)], and opioid prescribers per user. Geographic
variation was studied across Hospital Referral Regions. RESULTS: Most measures
peaked in 2010. The adjusted proportion with any opioid use was 43.9% in 2007,
44.7% in 2010, and 43.7% in 2011. The proportion with chronic use rose from 21.4%
in 2007 to 23.1% in 2011. Among chronic users: mean MED peaked at 81.3 mg in
2010, declining to 77.4 mg in 2011; in 2011, 19.8% received >= 100 mg MED; 10.4%
received >= 200 mg. In 2011, Hospital Referral Region-level measures varied
broadly (5th-95th percentile): any use: 33.0%-58.6%, chronic use: 13.9%-36.6%;
among chronic users, mean MED: 45 mg-125 mg; mean annual opioid prescribers: 2.4
3.7. CONCLUSIONS: Among these beneficiaries, opioid use was common. Although
intensity stabilized, the population using opioids chronically grew. Variation
shows a lack of a standardized approach and reveals regions with mean MED at
levels associated with overdose risk. Future work should assess outcomes, chronic
use predictors, and policies balancing pain control and safety.
PMID- 25119956
TI - Nontraumatic paecilomyces anterior segment infection: a pathognomonic clinical
appearance.
AB - PURPOSE: The aim of this study was to review a series of consecutive cases of
corneal and scleral infection by Paecilomyces spp. and to identify features of
clinical presentation and assess treatment modalities. METHODS: This
retrospective review of a case series included 22 patients with nontraumatic
Paecilomyces anterior segment infections who were seen in a tertiary referral
practice. Outcome measures were the number of eyes that were lost and visual
acuity in eyes that were saved. RESULTS: Twenty-two patients with Paecilomyces
corneal or scleral infection with no significant history of trauma or surgery
were identified over a 20-year period. Two distinct clinical presentations were
noted with 17 presenting with corneal infection and 5 initially presenting with
scleral infection, and all demonstrated a classical endothelial plaque and deep
stromal infiltrate. Almost all required single or multiple anterior segment
reconstructive surgeries together with systemic and topical antifungal agents.
The first 10 patients were treated with amphotericin B, whereas the remaining 12
patients were treated with voriconazole and 21 of 22 patients underwent surgery.
Paecilomyces spp. was identified from most intraocular specimens although corneal
fungal growth was noted only from deep corneal biopsies or corneal buttons
removed during corneal transplantation. Outcomes were better in the last 12
patients treated with voriconazole. CONCLUSIONS: Nontraumatic Paecilomyces
anterior segment infection presents with a pathognomonic clinical picture when
the cornea is the initial site of infection and later in scleral infections.
Early identification and aggressive treatment with extirpative surgery and
voriconazole may result in retention of the eye with useful vision.
PMID- 25119957
TI - Descemet membrane detachment after Nd: YAG laser capsulotomy in a patient with
fuchs dystrophy.
AB - PURPOSE: Descemet membrane detachment (DMD) is uncommon. It most frequently
occurs as a complication of intraocular surgery. The aim of this study was to
report a case of DMD after neodymium-doped yttrium aluminum garnet (Nd:YAG) laser
capsulotomy in a patient with Fuchs dystrophy. METHODS: We describe the case of
an 89-year-old man suffering from Fuchs dystrophy, who underwent cataract surgery
on his left eye. Three years later, the patient presented with posterior capsule
opacification, which was treated using Nd:YAG laser capsulotomy. The day after
the procedure, the patient came back for emergency treatment because of an acute
reduction in his vision caused by a DMD. RESULTS: Fifteen days after an initial
treatment involving the injection of air into the anterior chamber coupled with
ocular paracentesis, clinical examination revealed a significant improvement in
visual acuity, reduction in corneal edema, and reattachment of Descemet membrane.
These findings were confirmed using anterior segment optical coherence
tomography. CONCLUSIONS: To our knowledge, this is the first reported case of DMD
after Nd:YAG laser capsulotomy.
PMID- 25119958
TI - Wound healing process after corneal stromal thinning observed with anterior
segment optical coherence tomography.
AB - PURPOSE: The aim of this study was to observe the wound healing process after
corneal stromal thinning by using anterior segment optical coherence tomography
(AS-OCT) and a slit lamp. METHODS: Four patients with corneal stromal thinning (2
patients: corneal iron foreign bodies; 2 patients: keratitis) were included.
Serial AS-OCT and slit-lamp examinations were used to follow up the progress of
these patients. The thicknesses of the whole cornea and the corneal stroma were
measured with AS-OCT and compared with the findings observed during the slit-lamp
examination. RESULTS: AS-OCT showed that epithelial hypertrophy and hyperplasia
initially occurred in the area of the corneal stromal thinning; subsequently,
scar tissue formed in the area with an improvement in the thickness of the
corneal stroma. This wound healing process was observed in all 4 patients. The
scar tissue initially appeared opaque on slit-lamp examination and was
characterized by a high signal produced on AS-OCT, which was different from the
normal corneal stroma. The scar tissue gradually appeared clear on slit-lamp
examination; however, the high signal on AS-OCT remained. CONCLUSIONS: AS-OCT can
be used to detect the wound healing process of corneal stromal thinning.
PMID- 25119959
TI - Lens status as the single most important factor in endothelium protection after
vitreous surgery: a prospective study.
AB - PURPOSE: The aim of this study was to evaluate the effect of vitreous surgery on
the corneal endothelium. METHODS: A total of 113 eyes undergoing pars plana
vitrectomy for variable indications at a tertiary care center were included
prospectively. The mean age was 41 years (range, 9-84 years), and 60% were male.
The endothelial cell count was measured preoperatively and on postoperative day
1, 30, 90, and 180. The rate of endothelial cell loss was measured and analysis
performed based on gauge of surgery, lens status, and vitreous substitute used.
RESULTS: About 7.6% of endothelial cells were lost at postoperative day 1. This
rate had decreased to 2.5% in the first 30 days, 1.5% between days 30 and 90, and
1.4% between days 90 and 180. Significant difference in endothelial cell loss was
noted on day 1 between phakic (7.2%), pseudophakic (6.4%), and aphakic (11.4%)
eyes with similar results at 6 months. There was no significant difference
between the gauges of surgery (20 G vs. 23 G) or the vitreous substitutes used
(air vs. gas vs. silicone oil) on day 1 or at 6 months. CONCLUSIONS: Endothelial
decompensation is an important complication of vitreoretinal surgery. Precautions
should be taken in aphakics and patients requiring anterior segment manipulation.
Although there is immediate cell loss, the rate of cell loss approaches normative
values with time.
PMID- 25119960
TI - Healing rate of corneal erosions: comparison of the effect of chloramphenicol eye
drops and ointment and high-concentration hyaluronic acid in an animal model.
AB - PURPOSE: The aim of this study was to compare the effect of chloramphenicol eye
drops or ointment, high-concentration hyaluronic acid, or no treatment on
reepithelialization of corneal erosions in an experimental model. METHODS:
Uniform 6-mm corneal erosions were created in 23 rabbit eyes. The rabbits were
randomized to 4 treatment groups: (1) chloramphenicol eye drops group, (2)
chloramphenicol ointment, (3) hyaluronic acid 2.3%, and (4) untreated. Treatment
was administered every 8 hours until reepithelialization occurred. Eyes were
photographed every 8 hours with a cobalt blue-filtered light with fluorescein
drops until reepithelialization occurred. The area of the erosion at each time
point was analyzed. RESULTS: There were no significant differences in the
reepithelialization of the corneal erosion among the 3 treatment groups (72-75
hours, P > 0.05). The time was significantly shorter (51 hours) for the control
untreated group (P = 0.005). CONCLUSIONS: The use of chloramphenicol in the form
of eye drops or ointment for prophylaxis in corneal erosions has a similar effect
on the healing rate of the erosion. Both forms of the antibiotic and high
concentration hyaluronic acid had an effect of slowing down the healing of the
erosion when compared with when no treatment was given. Therefore, the decision
to treat erosions with eye drops or ointment can be based on the patient's
comfort.
PMID- 25119962
TI - Effects of subconjunctival tocilizumab versus bevacizumab in treatment of corneal
neovascularization in rabbits.
AB - PURPOSE: The aim of this study was to compare the antiangiogenic effects of
subconjunctival application of bevacizumab and tocilizumab on the regression of
corneal neovascularization (NV) in rabbits. METHODS: Corneal neovascularization
was induced in 48 eyes of 24 rabbits. Seven days after suture placement, the
rabbits were divided into 4 groups of 6 rabbits each and treated
subconjunctivally with 0.1 mL balanced salt solution (group 1), 0.1 mL
tocilizumab (0.25 mg per 0.1 mL and 2.5 mg per 0.1 mL, groups 2 and 3), or 0.1 mL
bevacizumab (2.5 mg per 0.1 mL) (group 4). Digital photographs of the eyes were
obtained and the surface areas of corneal neovascularization were measured on
days 7 and 14 after subconjunctival injections. On days 7 and 14, 3 rabbits were
randomly chosen and the eyes were extracted. Half of the corneal specimens were
analyzed histopathologically, and the other half were used to measure the
concentrations of vascular endothelial growth factor (VEGF) and IL-6 using a
multiplex bead assay, and the levels were compared with those of the controls.
RESULTS: The surface areas of induced corneal neovascularization were
significantly smaller in groups 3 and 4 (2.5 mg of tocilizumab and 2.5 mg of
bevacizumab) compared with the control group on days 7 and 14 (P < 0.05). Group 2
did not show significant difference from the control group on days 7 and 14.
There were no differences observed in the reduced neovascularization areas in
groups 3 and 4 on days 7 and 14. The concentrations of VEGF in groups 3 and 4
were significantly lower than in the control group, and IL-6 mRNA levels were
significantly lower in group 3 than in the other groups (P < 0.001) on days 7 and
14. Immunohistochemical analysis confirmed the reduced expression of VEGF in all
3 experimental groups compared with the control group. CONCLUSIONS: An
antiangiogenic effect was observed after subconjunctival injection of 2.5 mg
tocilizumab to an extent similar to that seen with 2.5 mg bevacizumab, which
indicates that subconjunctival application of tocilizumab is effective for the
inhibition of corneal neovascularization.
PMID- 25119963
TI - In vivo confocal microscopic features of corneal pseudodendritic lesions in
tyrosinemia type II.
AB - PURPOSE: To report the clinical and in vivo confocal microscopic (IVCM) findings
of corneal deposits in a patient with tyrosinemia type II. METHODS: The
pretreatment and 1-month posttreatment slit-lamp examination and IVCM findings of
a patient with tyrosinemia type II are described. RESULTS: A 12-year-old girl
diagnosed with tyrosinemia type II was evaluated for photophobia and bilateral
ocular discomfort of 1-year duration. The patient had been placed on topical
acyclovir treatment with the diagnosis of recurrent bilateral herpetic keratitis
during the previous 12 months. Slit-lamp examination revealed bilateral
dendritiform epithelial lesions in the central cornea, which stained poorly with
fluorescein. IVCM highlighted multiple hyperreflective linear crystalline
deposits at the level of superficial epithelium. One month after discontinuation
of acyclovir treatment and initiation of a protein-restricted diet therapy,
improvement in the patient's symptoms and regression of corneal epithelial
lesions was noted. Reduction in the extent of corneal deposits was also confirmed
with IVCM. CONCLUSIONS: Corneal involvement, secondary to hereditary tyrosinemia
type II, is characterized by pseudodendritic epithelial lesions on slit-lamp
examination and hyperreflective linear deposits in the superficial epithelium
using IVCM. These lesions may regress expeditiously with a low-protein diet. IVCM
may be a useful tool in the differential diagnosis of this disorder by
highlighting the crystalline structures in the superficial epithelial layers and
also in evaluating the response to the treatment in patients with tyrosinemia
type II.
PMID- 25119961
TI - Corneal graft rejection 10 years after penetrating keratoplasty in the cornea
donor study.
AB - PURPOSE: The aim of this study was to assess the effect of donor and recipient
factors on corneal allograft rejection and evaluate whether a rejection event was
associated with graft failure. METHODS: One thousand ninety subjects undergoing
penetrating keratoplasty for a moderate risk condition (principally Fuchs
dystrophy or pseudophakic corneal edema) were followed for up to 12 years.
Associations of baseline recipient and donor factors with the occurrence of a
rejection event were assessed in univariate and multivariate proportional hazards
models. RESULTS: Among 651 eyes with a surviving graft at 5 years, the 10-year
graft failure (+/-99% confidence interval) rates were 12% +/- 4% among eyes with
no rejection events in the first 5 years, 17% +/- 12% in eyes with at least 1
probable, but no definite rejection event, and 22% +/- 20% in eyes with at least
1 definite rejection event. The only baseline factor significantly associated
with a higher risk of definite graft rejection was a preoperative history of
glaucoma, particularly when previous glaucoma surgery had been performed and
glaucoma medications were being used at the time of transplant (10-year incidence
35% +/- 23% compared with 14% +/- 4% in eyes with no history of
glaucoma/intraocular pressure treatment, P = 0.008). CONCLUSIONS: Patients who
experienced a definite rejection event frequently developed graft failure raising
important questions as to how we might change acute and long-term corneal graft
management. Multivariate analysis indicated that previous use of glaucoma
medications and glaucoma filtering surgery was a significant risk factor related
to a definite rejection event.
PMID- 25119964
TI - Changes in color vision and contrast sensitivity after descemet membrane
endothelial keratoplasty for fuchs endothelial dystrophy.
AB - PURPOSE: The aim of this study is to evaluate contrast sensitivity, color vision,
and subjective patient satisfaction after Descemet membrane endothelial
keratoplasty (DMEK) in patients with bilateral Fuchs endothelial dystrophy (FED).
METHODS: From a group of 500 DMEK surgeries performed in our center, patients
with a history of bilateral FED and unilateral DMEK were identified. A total of
29 patients were included in the study and divided into 2 groups: phakic (n = 12)
and pseudophakic unilateral DMEK (n = 17) and their contralateral, untreated FED
affected eye. In addition, a control group of 10 healthy eyes of 10 patients was
included. Pelli-Robson contrast sensitivity and Farnsworth-Munsell 100 hue color
vision tests were performed. Subjective optical quality was graded with a
questionnaire. RESULTS: Compared with untreated FED-affected eyes, best spectacle
corrected visual acuity was higher after DMEK in phakic and pseudophakic eyes (P
= 0.030 and P < 0.001, respectively); a similar result was obtained for contrast
sensitivity (P < 0.001 and P < 0.001, respectively). Color vision did not differ
between untreated FED-affected and DMEK-operated eyes in the phakic group (P =
0.802) and the pseudophakic group (P = 0.227). Subjective optical quality was
better in DMEK-operated eyes than in untreated FED-affected eyes in the phakic
group (P < 0.001) and in the pseudophakic group (P < 0.001). CONCLUSIONS: In FED,
DMEK may not only be effective for obtaining a higher visual acuity but
particularly improving the contrast sensitivity may also lead to better
subjective optical performance. Although frequently mentioned spontaneously by
patients, an objective change in color vision could not be substantiated. Hence,
quantifying contrast sensitivity before surgery may aid in the decision for
surgery, and in the evaluation of surgical outcome.
PMID- 25119965
TI - Phytochrome-interacting transcription factors PIF4 and PIF5 induce leaf
senescence in Arabidopsis.
AB - Plants initiate senescence to shed photosynthetically inefficient leaves. Light
deprivation induces leaf senescence, which involves massive transcriptional
reprogramming to dismantle cellular components and remobilize nutrients. In
darkness, intermittent pulses of red light can inhibit senescence, likely via
phytochromes. However, the precise molecular mechanisms transducing the signals
from light perception to the inhibition of senescence remain elusive. Here, we
show that in Arabidopsis, dark-induced senescence requires phytochrome
interacting transcription factors PIF4 and PIF5 (PIF4/PIF5). ELF3 and phytochrome
B inhibit senescence by repressing PIF4/PIF5 at the transcriptional and post
translational levels, respectively. PIF4/PIF5 act in the signalling pathways of
two senescence-promoting hormones, ethylene and abscisic acid, by directly
activating expression of EIN3, ABI5 and EEL. In turn, PIF4, PIF5, EIN3, ABI5 and
EEL directly activate the expression of the major senescence-promoting NAC
transcription factor ORESARA1, thus forming multiple, coherent feed-forward
loops. Our results reveal how classical light signalling connects to senescence
in Arabidopsis.
PMID- 25119966
TI - Accuracy of magnetic resonance imaging in planning the osseous resection margins
of bony tumours in the proximal femur: based on coronal T1-weighted versus STIR
images.
AB - OBJECTIVE: Assessment of the extent of tumours using magnetic resonance imaging
(MRI) is the basis for bone resection in limb-salvage surgery. We aimed to
compare the accuracy of T1-weighted MRI and STIR sequences in measuring the
extent of proximal femoral tumours, using the macroscopic specimens as the gold
standard for comparison. MATERIALS AND METHODS: We compared single coronal T1
weighted with STIR sequences in 34 proximal femoral tumours, using bivalved
resected macroscopic tumours for comparison. After randomisation, four observers
measured longitudinal osseous tumour extent using MRI and specimen photographs on
two separate occasions, 3 weeks apart. RESULTS: There were 25 metastatic tumours,
8 chondrosarcomas and 1 myeloma. Eight patients presented with pathological
fractures. The Pearson's correlation coefficient for comparison of T1 with
macroscopic tumours was 0.91 (95% confidence interval [CI]: 0.83 to 0.96) for all
observers and 0.90 (95% CI: 0.81 to 0.95) for STIR images. This difference was
not statistically significant, and T1 and STIR sequence measurements had similar
precision and accuracy. Bland-Altman plots showed T1-weighted imaging to be
unbiased, whereas STIR sequences were biased and had systematic error. Moreover,
STIR measurements overestimated tumour size by 6.4 mm (95% CI: -26.9 to 39.7 mm)
and 2 patients were outliers. T1 measurements were closer to the macroscopic
measurements with a mean difference of 1.3 mm (95% CI: -28.9 mm to 31.5 mm), with
3 patients falling outside of this. The variance was greater for STIR
measurements. This difference between T1 and STIR measurements was statistically
significant (p = 0.000003). The intra-observer reliability between separate
measurements for MRI and specimen photographs achieved interclass correlation
coefficients of 0.97, 0.96 and 0.95 (T1, STIR and macroscopic tumour
respectively). T1 had greater interobserver correlation than for STIR and
macroscopic tumour measurements (0.88 vs 0.85 and 0.85 respectively). These
differences in interclass correlation were not statistically significant.
CONCLUSION: This study has shown T1-weighted MRI sequences to be unbiased
compared with STIR sequences at determining intra-osseous tumour extent. STIR
overestimates the length of bone tumours. T1 is therefore preferred for pre
operative planning for the resection of bone tumours.
PMID- 25119967
TI - FGFR3-related condition: a skeletal dysplasia with similarities to thanatophoric
dysplasia and SADDAN due to Lys650Met.
AB - Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene account for six
related skeletal dysplasia conditions: achondroplasia, hypochondroplasia,
thanatophoric dysplasia types 1 and 2, SADDAN (severe achondroplasia with
developmental delay and acanthosis nigricans), and platyspondylic lethal skeletal
dysplasia, San Diego type. This group of disorders has very characteristic
clinical and radiologic features, which distinguish them from other skeletal
dysplasias. They display a spectrum of severity in the skeletal findings, ranging
from relatively mild hypochondroplasia to lethal thanatophoric dysplasia. We
report a patient who has the missense FGFR3 mutation, Lys650Met, previously
reported in association only with SADDAN, who exhibits some findings similar to
both thanatophoric dysplasia (types 1 and 2) in addition to those findings
characteristic of SADDAN.
PMID- 25119969
TI - PMCA4 (ATP2B4) mutation in familial spastic paraplegia.
AB - Familial spastic paraplegia (FSP) is a heterogeneous group of disorders
characterized primarily by progressive lower limb spasticity and weakness. More
than 50 disease loci have been described with different modes of inheritance. In
this study, we identified a novel missense mutation (c.803G>A, p.R268Q) in the
plasma membrane calcium ATPase (PMCA4, or ATP2B4) gene in a Chinese family with
autosomal dominant FSP using whole-exome sequencing and confirmed with Sanger
sequencing. This mutation co-segregated with the phenotype in the six family
members studied and is predicted to be pathogenic when multiple deleteriousness
predictions were combined. This novel R268Q mutation was not present in over
7,000 subjects in public databases, and over 1,000 Han Chinese in our database.
Prediction of potential functional consequence of R268Q mutation on PMCA4 by
computational modeling revealed that this mutation is located in protein
aggregation-prone segment susceptible to protein misfolding. Analysis for
thermodynamic protein stability indicated that this mutation destabilizes the
PMCA4 protein structure with higher folding free energy. As PMCA4 functions to
maintain neuronal calcium homeostasis, our result showed that calcium
dysregulation may be associated with the pathogenesis of FSP.
PMID- 25119968
TI - The role of nibrin in doxorubicin-induced apoptosis and cell senescence in
Nijmegen Breakage Syndrome patients lymphocytes.
AB - Nibrin plays an important role in the DNA damage response (DDR) and DNA repair.
DDR is a crucial signaling pathway in apoptosis and senescence. To verify whether
truncated nibrin (p70), causing Nijmegen Breakage Syndrome (NBS), is involved in
DDR and cell fate upon DNA damage, we used two (S4 and S3R) spontaneously
immortalized T cell lines from NBS patients, with the founding mutation and a
control cell line (L5). S4 and S3R cells have the same level of p70 nibrin,
however p70 from S4 cells was able to form more complexes with ATM and BRCA1.
Doxorubicin-induced DDR followed by cell senescence could only be observed in L5
and S4 cells, but not in the S3R ones. Furthermore the S3R cells only underwent
cell death, but not senescence after doxorubicin treatment. In contrary to
doxorubicin treatment, cells from all three cell lines were able to activate the
DDR pathway after being exposed to gamma-radiation. Downregulation of nibrin in
normal human vascular smooth muscle cells (VSMCs) did not prevent the activation
of DDR and induction of senescence. Our results indicate that a substantially
reduced level of nibrin or its truncated p70 form is sufficient to induce DNA
damage dependent senescence in VSMCs and S4 cells, respectively. In doxorubicin
treated S3R cells DDR activation was severely impaired, thus preventing the
induction of senescence.
PMID- 25119970
TI - Posttranslational protein modifications by reactive nitrogen and chlorine species
and strategies for their prevention and elimination.
AB - Proteins are subject to various posttranslational modifications, some of them
being undesired from the point of view of metabolic efficiency. Prevention of
such modifications is expected to provide new means of therapy of diseases and
decelerate the process of aging. In this review, modifications of proteins by
reactive nitrogen species and reactive halogen species, is briefly presented and
means of prevention of these modifications and their sequelae are discussed,
including the denitrase activity and inhibitors of myeloperoxidase.
PMID- 25119974
TI - Bromide: a pressing issue to address in China's shale gas extraction.
PMID- 25119972
TI - Targeting BRAF mutant metastatic colorectal cancer: clinical implications and
emerging therapeutic strategies.
AB - Increasing knowledge of the underlying signaling pathways and molecular defects
involved in colorectal cancer growth or progression enabled the discovery of
several prognostic and predictive biomarkers, leading to the development of novel
molecularly targeted therapies. The mitogen-activated protein kinase (MAPK)
signaling pathway plays a critical role in colorectal cancer progression.
Mutations in BRAF, a principal effector of Ras in this signaling cascade, are
found in 10 % of colorectal cancer and play a clear pathogenic role, particularly
in patients with metastatic disease. Intense efforts have therefore focused on
targeting BRAF as an oncogenic driver, with mixed early results. This article
summarizes the molecular and clinical features of BRAF mutant colorectal cancer,
the prognostic and predictive role of BRAFV600E mutation in colorectal cancer,
initial clinical trial results in targeting BRAFV600E, and the more recent
preclinical insights into potential mechanisms of resistance to BRAF inhibition
that have now led to a number of rationale-driven combination therapeutic
strategies.
PMID- 25119973
TI - Rebiopsy during disease progression in patients treated by TKI for oncogene
addicted NSCLC.
AB - All lung cancer patients with mutant epidermal growth factor receptor (EGFR) or
rearranged EML4-ALK eventually develop acquired resistance to treatment. Rebiopsy
may give insight into the resistance mechanisms and direct further lines of
treatment. Here, we evaluate the potential interest and limitations of rebiopsy.
Patients with mutant EGFR or rearranged EML4-ALK non-small cell lung cancer
(NSCLC) and acquired resistance to tyrosine kinase inhibitors were included in a
retrospective study to determine the percentage of patients who underwent
rebiopsy and whether rebiopsy would have been possible, or not, in the remaining
patients. In a cohort of 84 patients from 6 institutions, a biopsy had been
performed in 39 cases. Biopsy samples were sufficient for histopathological or
cytological examination in 35 cases (89.7 %). Complete or partial response had
been observed in 84.5 % of patients whose cancer further progressed and who
underwent rebiopsy. A biopsy could have been considered in 30 of the 45 remaining
patients. Those with brain (N = 9) and bone (N = 2) metastases and/or with
contraindications (N = 6) were excluded (two patients had both brain metastases
and a contraindication). The rebiopsy target was thoracic in 62 % of cases and on
distant metastases in 38 % of cases. Patients with NSCLC and an activating
mutation could undergo a rebiopsy in 72 % of cases. A response to treatment does
not preclude the possibility of rebiopsy at the time of progression.
PMID- 25119975
TI - Synthesis of colloidal microgels using oxygen-controlled flow lithography.
AB - We report a synthesis approach based on stop-flow lithography (SFL) for
fabricating colloidal microparticles with any arbitrary 2D-extruded shape. By
modulating the degree of oxygen inhibition during synthesis, we achieved
previously unattainable particle sizes. Brownian diffusion of colloidal discs in
bulk suggests the out-of-plane dimension can be as small as 0.8 MUm, which agrees
with confocal microscopy measurements. We measured the hindered diffusion of
microdiscs near a solid surface and compared our results to theoretical
predictions. These colloidal particles can also flow through physiological
microvascular networks formed by endothelial cells undergoing vasculogensis under
minimal hydrostatic pressure (~5 mm H2O). This versatile platform creates future
opportunities for on-chip parametric studies of particle geometry effects on
particle passage properties, distribution and cellular interactions.
PMID- 25119976
TI - Treating the violent patient with psychosis or impulsivity utilizing
antipsychotic polypharmacy and high-dose monotherapy.
AB - Insufficient treatment of psychosis often manifests as violent and aggressive
behaviors that are dangerous to the patient and others, and that warrant
treatment strategies which are not considered first-line, evidence-based
practices. Such treatment strategies include both antipsychotic polypharmacy
(simultaneous use of 2 antipsychotics) and high-dose antipsychotic monotherapy.
Here we discuss the hypothesized neurobiological substrates of various types of
violence and aggression, as well as providing arguments for the use of
antipsychotic polypharmacy and high-dose monotherapy to target dysfunctional
neurocircuitry in the subpopulation of patients that is treatment-resistant,
violent, and aggressive. In this review, we focus primarily on the data
supporting the use of second-generation, atypical antipsychotics both at high
doses and in combination with other antipsychotics.
PMID- 25119977
TI - Zirconium complexes of phenylene-bridged {ONSO} ligands: coordination chemistry
and stereoselective polymerization of rac-lactide.
AB - Sequential tetradentate dianionic thio-imine diphenolate ligands featuring an
ortho-phenylene core and their zirconium complexes are described for the first
time. Ligands that include different combinations of bulky-alkyl groups and halo
groups on the two phenol arms were prepared by a substitution/condensation
reaction sequence. An unexpected fac-fac wrapping mode was found in the solid
state for the ligands in the octahedral [{ONSO}Zr(O(t)Bu)2] complexes. The
complexes were all fluxional, and the barrier for enantiomer interconversion was
found to depend on the phenolate substituents. The complexes were found to
catalyze the polymerization of rac-lactide to poly(lactic acid) in solution with
polymer tacticities varying from heterotactic to atactic which showed correlation
to the nature of phenolate substituents but not to the degree of complex
fluxionality.
PMID- 25119978
TI - Binding free energy based structural dynamics analysis of HIV-1 RT RNase H
inhibitor complexes.
AB - Accurate prediction of binding free energies associated with small molecules
binding to a receptor is a major challenge in drug design processes. To achieve
this goal many computational methods have been developed ranging from highly
efficient empirical based docking schemes to high accuracy methods based on e.g.
free energy calculations. In this study, binding affinity predictions for a set
of HIV-1 RNase H inhibitors have been performed using MM-PB(GB)/SA methods. The
current study describes in detail how the choice of initial ligand structures,
e.g. protonation states, impacts the predicted ranking of the compounds. In
addition we study the structural dynamics of the RNase H complexes using
molecular dynamics. The role of each residue contribution to the overall binding
free energy is also explored and used to explain the variations in the inhibition
potency. The results reported here can be useful for design of small molecules
against RNase H activity in the development of effective drugs for HIV treatment.
PMID- 25119979
TI - Perspectives in Pediatric Pathology, Chapter 12. Congenital Epididymal Anomalies.
PMID- 25119980
TI - Remember that? Or does it just seem familiar? A sophisticated test for assessing
memory in humans and animals reveals a specific cognitive impairment following
general anesthesia in infancy.
PMID- 25119982
TI - Local coding based matching kernel method for image classification.
AB - This paper mainly focuses on how to effectively and efficiently measure visual
similarity for local feature based representation. Among existing methods,
metrics based on Bag of Visual Word (BoV) techniques are efficient and
conceptually simple, at the expense of effectiveness. By contrast, kernel based
metrics are more effective, but at the cost of greater computational complexity
and increased storage requirements. We show that a unified visual matching
framework can be developed to encompass both BoV and kernel based metrics, in
which local kernel plays an important role between feature pairs or between
features and their reconstruction. Generally, local kernels are defined using
Euclidean distance or its derivatives, based either explicitly or implicitly on
an assumption of Gaussian noise. However, local features such as SIFT and HoG
often follow a heavy-tailed distribution which tends to undermine the motivation
behind Euclidean metrics. Motivated by recent advances in feature coding
techniques, a novel efficient local coding based matching kernel (LCMK) method is
proposed. This exploits the manifold structures in Hilbert space derived from
local kernels. The proposed method combines advantages of both BoV and kernel
based metrics, and achieves a linear computational complexity. This enables
efficient and scalable visual matching to be performed on large scale image sets.
To evaluate the effectiveness of the proposed LCMK method, we conduct extensive
experiments with widely used benchmark datasets, including 15-Scenes,
Caltech101/256, PASCAL VOC 2007 and 2011 datasets. Experimental results confirm
the effectiveness of the relatively efficient LCMK method.
PMID- 25119981
TI - Vaccine-mediated immune responses to experimental pulmonary Cryptococcus gattii
infection in mice.
AB - Cryptococcus gattii is a fungal pathogen that can cause life-threatening
respiratory and disseminated infections in immune-competent and immune-suppressed
individuals. Currently, there are no standardized vaccines against cryptococcosis
in humans, underlying an urgent need for effective therapies and/or vaccines. In
this study, we evaluated the efficacy of intranasal immunization with C. gattii
cell wall associated (CW) and/or cytoplasmic (CP) protein preparations to induce
protection against experimental pulmonary C. gattii infection in mice. BALB/c
mice immunized with C. gattii CW and/or CP protein preparations exhibited a
significant reduction in pulmonary fungal burden and prolonged survival following
pulmonary challenge with C. gattii. Protection was associated with significantly
increased pro-inflammatory and Th1-type cytokine recall responses, in vitro and
increased C. gattii-specific antibody production in immunized mice challenged
with C. gattii. A number of immunodominant proteins were identified following
immunoblot analysis of C. gattii CW and CP protein preparations using sera from
immunized mice. Immunization with a combined CW and CP protein preparation
resulted in an early increase in pulmonary T cell infiltrates following challenge
with C. gattii. Overall, our studies show that C. gattii CW and CP protein
preparations contain antigens that may be included in a subunit vaccine to induce
prolonged protection against pulmonary C. gattii infection.
PMID- 25119983
TI - Diversity of selected Lupinus angustifolius L. genotypes at the phenotypic and
DNA level with respect to microscopic seed coat structure and thickness.
AB - The paper investigates seed coat characteristics (as a percentage of overall seed
diameter) in Lupinus angustifolius L., a potential forage crop. In the study ten
L. angustifolius genotypes, including three Polish cultivars, two Australian
cultivars, three mutants originated from cv. 'Emir', and one Belarusian and one
Australian breeding line were evaluated. The highest seed coat percentage was
recorded in cultivars 'Sonet' and 'Emir'. The lowest seed coat thickness
percentage (below 20%) was noted for breeding lines 11257-19, LAG24 and cultivar
'Zeus' (17.87%, 18.91% 19.60%, respectively). Despite having low seed weight, the
Australian line no. 11257-19 was characterized by a desirable proportion of seed
coat to the weight of seeds. In general, estimation of the correlation
coefficient indicated a tendency that larger seeds had thinner coats. Scanning
Electron Microscopy images showed low variation of seed coat sculpture and the
top of seeds covered with a cuticle. Most of the studied genotypes were
characterized by a cristatepapillate seed coat surface, formed by elongated
polygonal cells. Only breeding line no. 11267-19 had a different shape of the
cells building the surface layer of the coat. In order to illustrate genetic
diversity among the genotypes tested, 24 ISSR primers were used. They generated a
total of 161 polymorphic amplification products in 10 evaluated narrow-leaved
lupin genotypes.
PMID- 25119984
TI - Differential responses of herbivores and herbivory to management in temperate
European beech.
AB - Forest management not only affects biodiversity but also might alter ecosystem
processes mediated by the organisms, i.e. herbivory the removal of plant biomass
by plant-eating insects and other arthropod groups. Aiming at revealing general
relationships between forest management and herbivory we investigated aboveground
arthropod herbivory in 105 plots dominated by European beech in three different
regions in Germany in the sun-exposed canopy of mature beech trees and on beech
saplings in the understorey. We separately assessed damage by different guilds of
herbivores, i.e. chewing, sucking and scraping herbivores, gall-forming insects
and mites, and leaf-mining insects. We asked whether herbivory differs among
different forest management regimes (unmanaged, uneven-aged managed, even-aged
managed) and among age-classes within even-aged forests. We further tested for
consistency of relationships between regions, strata and herbivore guilds. On
average, almost 80% of beech leaves showed herbivory damage, and about 6% of leaf
area was consumed. Chewing damage was most common, whereas leaf sucking and
scraping damage were very rare. Damage was generally greater in the canopy than
in the understorey, in particular for chewing and scraping damage, and the
occurrence of mines. There was little difference in herbivory among differently
managed forests and the effects of management on damage differed among regions,
strata and damage types. Covariates such as wood volume, tree density and plant
diversity weakly influenced herbivory, and effects differed between herbivory
types. We conclude that despite of the relatively low number of species attacking
beech; arthropod herbivory on beech is generally high. We further conclude that
responses of herbivory to forest management are multifaceted and environmental
factors such as forest structure variables affecting in particular microclimatic
conditions are more likely to explain the variability in herbivory among beech
forest plots.
PMID- 25119985
TI - Modulation of GABA-A receptors of astrocytes and STC-1 cells by taurine
structural analogs.
AB - Taurine activates and modulates GABA receptors in vivo as well as those expressed
in heterologous systems. This study aimed to determine whether the structural
analogs of taurine: homotaurine and hypotaurine, have the ability to activate
GABA-A receptors that include GABArho subunits. The expression of GABA-A
receptors containing GABArho has been reported in the STC-1 cells and astrocytes.
In both cell types, taurine, homo-, and hypotaurine gated with low efficiency a
picrotoxin-sensitive GABA-A receptor. The known bimodal modulatory effect of
taurine on GABArho receptors was not observed; however, differences between the
activation and deactivation rates were detected when they were perfused together
with GABA. In silico docking simulations suggested that taurine, hypo-, and
homotaurine do not form a cation-pi interaction such as that generated by GABA in
the agonist-binding site of GABArho. This observation complements the
electrophysiological data suggesting that taurine and its analogs act as partial
agonists of GABA-A receptors. All the observations above suggest that the
structural analogs of taurine are partial agonists of GABA-A receptors that
occupy the agonist-binding site, but their structures do not allow the proper
interaction with the receptor to fully gate its Cl(-) channel.
PMID- 25119986
TI - Adjuvant chemotherapy after radical cystectomy for bladder cancer: a comparative
study using inverse-probability-of-treatment weighting.
AB - OBJECTIVES: The role of adjuvant chemotherapy (AC) after radical cystectomy for
bladder cancer remains unclear. This study evaluated the benefits of cisplatin
based AC plus surgery versus surgery alone in patients with bladder cancer.
MATERIALS AND METHODS: The medical records of 746 patients who underwent radical
cystectomy for bladder cancer were reviewed. The association between AC and
survival was analyzed using Cox regression models. To reduce the impact of
treatment selection bias and potential confounding in an observational study,
significant differences in patient characteristics were rigorously adjusted using
inverse-probability-of-treatment weighting (IPTW). RESULTS: The cohort consisted
of 746 patients (664 men and 82 women) of mean age 62.4 years and median follow
up of 64.3 months (range, 1-231.4 months). Of these patients, 176 (23.6%)
received AC after cystectomy and 570 (76.4%) underwent cystectomy alone. Patients
who received AC were significantly younger (60 vs. 63 years, p = 0.001) and
significantly more likely to have high pathologic T stage (p = 0.001), lymph node
metastasis (p = 0.001), high grade (p = 0.001), and lymphovascular invasion (p =
0.001) than patients who underwent cystectomy alone. Multivariable analysis
showed a cancer-specific survival (CSS) benefit for AC [hazard ratio (HR) 0.56,
95% confidence interval (CI) 0.39-0.80, p = 0.002], as did low pathologic T
stage, absence of lymph node metastasis, and absence of lymphovascular invasion.
After IPTW adjustment for baseline characteristics, AC remained an independent
predictor of CSS (HR 0.83, 95% CI 0.69-0.99, p = 0.043). CONCLUSIONS: Cisplatin
based AC after radical cystectomy had survival benefits in patients with bladder
cancer, even after IPTW adjustment for confounding variables.
PMID- 25119987
TI - Severe gastrointestinal bleeding in patients with locally advanced head and neck
squamous cell carcinoma treated by concurrent radiotherapy and Cetuximab.
AB - PURPOSE: Concurrent administration of Cetuximab with radiotherapy (Cetuximab
radiation) has been accepted as an alternative option for locally advanced head
and neck squamous cell carcinoma (HNSCC). The purpose of this study was to
retrospectively compare complications of Cetuximab-radiation with those of
concurrent chemoradiation (cCRT) with a special concern on gastrointestinal (GI)
hemorrhage associated with Cetuximab-radiation. METHODS: Indication of Cetuximab
radiation/cCRT for locally advanced HNSCC was primary, postoperative adjuvant, or
salvage after recurrence. Our first choice for patients with advanced HNSCC was
cCRT; however, if patients did not have enough organ function but with a
favorable performance status, Cetuximab-radiation was applied. RESULTS: From
April 2013 to March 2014, 30 patients were identified who were treated with
Cetuximab-radiation or cCRT and each cohort consisted of 15 patients. Patients in
Cetuximab-radiation cohort suffered from a statistically higher rate of G3/4
dermatitis compared with cCRT cohort (80 vs. 13.3%, respectively, p < 0.001).
More patients required unexpected hospitalization due to deterioration of their
general condition and total parenteral nutrition in Cetuximab-radiation cohort (p
= 0.011 and p = 0.025, respectively). While none experienced GI bleeding in cCRT
cohort, four patients experienced GI bleeding including two grade 4 bleeding in
Cetuximab-radiation cohort (p = 0.05). CONCLUSIONS: It is probable that there
exists a group of patients who are susceptible for Cetuximab-radiation not only
in terms of well-known dermatitis and mucositis but also of gastrointestinal
complications.
PMID- 25119988
TI - Genome analysis of Bacillus amyloliquefaciens Subsp. plantarum UCMB5113: a
rhizobacterium that improves plant growth and stress management.
AB - The Bacillus amyloliquefaciens subsp. plantarum strain UCMB5113 is a Gram
positive rhizobacterium that can colonize plant roots and stimulate plant growth
and defense based on unknown mechanisms. This reinforcement of plants may provide
protection to various forms of biotic and abiotic stress. To determine the
genetic traits involved in the mechanism of plant-bacteria association, the
genome sequence of UCMB5113 was obtained by assembling paired-end Illumina reads.
The assembled chromosome of 3,889,532 bp was predicted to encode 3,656 proteins.
Genes that potentially contribute to plant growth promotion such as indole-3
acetic acid (IAA) biosynthesis, acetoin synthesis and siderophore production were
identified. Moreover, annotation identified putative genes responsible for non
ribosomal synthesis of secondary metabolites and genes supporting environment
fitness of UCMB5113 including drug and metal resistance. A large number of genes
encoding a diverse set of secretory proteins, enzymes of primary and secondary
metabolism and carbohydrate active enzymes were found which reflect a high
capacity to degrade various rhizosphere macromolecules. Additionally, many
predicted membrane transporters provides the bacterium with efficient uptake
capabilities of several nutrients. Although, UCMB5113 has the possibility to
produce antibiotics and biosurfactants, the protective effect of plants to
pathogens seems to be indirect and due to priming of plant induced systemic
resistance. The availability of the genome enables identification of genes and
their function underpinning beneficial interactions of UCMB5113 with plants.
PMID- 25119989
TI - Cyclophilin A (CypA) interacts with NF-kappaB subunit, p65/RelA, and contributes
to NF-kappaB activation signaling.
AB - BACKGROUND: Peptidyl-prolyl isomerase cyclophilin A (CypA) plays important roles
in signaling, protein translocation, inflammation, and cancer formation. However,
little is known about the mechanisms by which CypA exerts its effects. C57BL/6
Ppia (encoding CypA)-deficient embryonic fibroblasts show reduced activation of
the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB),
the p65/RelA subunit, suggesting that CypA may mediate modulation of NF-kappaB
activity to exert its biological effects. METHODOLOGY: Western blotting and qRT
PCR analyses were used to evaluate the association of CypA deficiency with
reduced activation of NF-kappaB/p65 at the protein level. GST pull-down and co
immunoprecipitation were used to examine interactions between CypA and p65/RelA.
Truncation mutants and site-directed mutagenesis were used to determine the
sequences of p65/RelA required for interactions with CypA. Enhancement of
p65/RelA nuclear translocation by CypA was assessed by co-transfection and
immunofluorescent imaging. Treatment of cells with cycloheximide that were
harvested at various time points for Western blot analyses was carried out to
evaluate p65/RelA protein stability. The functional activity of NF-kappaB was
assessed by electrophoretic mobility-shift assays (EMSA), luciferase assays, and
changes in expression levels of target genes. RESULTS: GST pull-down assays in
vitro and co-immunoprecipitation analyses in vivo provided evidence for protein
protein interactions. These interactions were further supported by identification
of a CypA-binding consensus-like sequence within NF-kappaB subunit p65 at the N
terminal 170-176 amino acid residues. Significantly, CypA provided stability for
NF-kappaB p65 and promoted NF-kappaB p65 nuclear translocation, resulting in
increased nuclear accumulation and enhanced NF-kappaB activity. CONCLUSIONS: Our
findings revealed important mechanisms that regulate NF-kappaB activation, and
offer new insights into the role of CypA in aberrant activation of NF-kappaB
mediated signaling for altered expression of its target genes, resulting in
pathological effects in various diseases.
PMID- 25119991
TI - Comparative analysis of seven viral nuclear export signals (NESs) reveals the
crucial role of nuclear export mediated by the third NES consensus sequence of
nucleoprotein (NP) in influenza A virus replication.
AB - The assembly of influenza virus progeny virions requires machinery that exports
viral genomic ribonucleoproteins from the cell nucleus. Currently, seven nuclear
export signal (NES) consensus sequences have been identified in different viral
proteins, including NS1, NS2, M1, and NP. The present study examined the roles of
viral NES consensus sequences and their significance in terms of viral
replication and nuclear export. Mutation of the NP-NES3 consensus sequence
resulted in a failure to rescue viruses using a reverse genetics approach,
whereas mutation of the NS2-NES1 and NS2-NES2 sequences led to a strong reduction
in viral replication kinetics compared with the wild-type sequence. While the
viral replication kinetics for other NES mutant viruses were also lower than
those of the wild-type, the difference was not so marked. Immunofluorescence
analysis after transient expression of NP-NES3, NS2-NES1, or NS2-NES2 proteins in
host cells showed that they accumulated in the cell nucleus. These results
suggest that the NP-NES3 consensus sequence is mostly required for viral
replication. Therefore, each of the hydrophobic (Phi) residues within this NES
consensus sequence (Phi1, Phi2, Phi3, or Phi4) was mutated, and its viral
replication and nuclear export function were analyzed. No viruses harboring NP
NES3 Phi2 or Phi3 mutants could be rescued. Consistent with this, the NP-NES3
Phi2 and Phi3 mutants showed reduced binding affinity with CRM1 in a pull-down
assay, and both accumulated in the cell nucleus. Indeed, a nuclear export assay
revealed that these mutant proteins showed lower nuclear export activity than the
wild-type protein. Moreover, the Phi2 and Phi3 residues (along with other Phi
residues) within the NP-NES3 consensus were highly conserved among different
influenza A viruses, including human, avian, and swine. Taken together, these
results suggest that the Phi2 and Phi3 residues within the NP-NES3 protein are
important for its nuclear export function during viral replication.
PMID- 25119992
TI - Kinetic analysis of the multistep aggregation mechanism of monoclonal antibodies.
AB - We investigate by kinetic analysis the aggregation mechanism of two monoclonal
antibodies belonging to the IgG1 and IgG2 subclass under thermal stress. For each
IgG, we apply a combination of size exclusion chromatography and light scattering
techniques to resolve the time evolution of the monomer, dimer, and trimer
concentrations, as well as the average molecular weight and the average
hydrodynamic radius of the aggregate distribution. By combining the detailed
experimental characterization with a theoretical kinetic model based on
population balance equations, we extract relevant information on the contribution
of the individual elementary steps on the global aggregation process. The
analysis shows that the two molecules follow different aggregation pathways under
the same operating conditions. In particular, while the monomer depletion of the
IgG1 is found to be rate-limited by monomeric conformational changes, bimolecular
collision is identified as the rate-limiting step in the IgG2 aggregation
process. The measurement of the microscopic rate constants by kinetic analysis
allows the quantification of the protein-protein interaction potentials expressed
in terms of the Fuchs stability ratio (W). It is found that the antibody
solutions exhibit large W values, which are several orders of magnitude larger
than the values computed in the frame of the DLVO theory. This indicates that,
besides net electrostatic repulsion, additional effects delay the aggregation
kinetics of the antibody solutions with respect to diffusion-limited conditions.
These effects likely include the limited efficiency of the collision events due
to the presence of a limited number of specific aggregation-prone patches on the
heterogeneous protein surface, and the contribution of additional repulsive non
DLVO forces to the protein-protein interaction potential, such as hydration
forces.
PMID- 25119993
TI - Isoegomaketone induces apoptosis in SK-MEL-2 human melanoma cells through
mitochondrial apoptotic pathway via activating the PI3K/Akt pathway.
AB - Isoegomaketone (IK) is a major biologically active component of Perilla
frutescens. In this study, we investigated the contribution of reactive oxygen
species (ROS) to IK-induced apoptosis in human melanoma SK-MEL-2 cells. We found
that IK inhibited the proliferation of SK-MEL-2 human melanoma cells in a dose
dependent manner. IK also induced sub-G1 DNA accumulation, formation of apoptotic
bodies, nuclear condensation, and a DNA ladder in SK-MEL-2 cells. IK also induced
activation of caspase-3 and -9, whereas caspase-8 was unaffected. Further, N
acetyl-L-cysteine (NAC, ROS scavenger) treatment to SK-MEL-2 cells significantly
reduced IK-induced cell death. Pretreatment of NAC to SK-MEL-2 cells followed by
100 uM IK reduced the protein levels of Bax and cytochrome c as well as PARP
cleavage, whereas the protein level of Bcl-2 increased. Moreover, IK inhibited
the phosphorylation of AKT/mTOR protein and cell proliferation induced by
LY294002, a PI3K inhibitor. In conclusion, IK-induced ROS generation regulates
cell growth inhibition and it induces apoptosis through caspase-dependent and
independent pathways via modulation of PI3K/AKT signaling in SK-MEL-2 cells.
PMID- 25119994
TI - Preparation and in vitro/in vivo characterization of tranilast-AMP clay complex
for improving drug dissolution and bioavailability.
AB - The present study aimed to develop an effective oral formulation of tranilast
(TL), a poorly soluble anti-inflammatory drug, via the formation of drug complex
with 3-aminopropyl functionalized magnesium phyllosilicate (AMP clay) and improve
the pH-dependent drug dissolution and bioavailability of TL. The drug-clay
complex (TL-AMP complex) was prepared by co-precipitation method and its
structural properties were characterized by X-ray powder diffraction, Fourier
transform infrared spectroscopy and transmission electron microscopy. The
dissolution profiles of TL-AMP complex were evaluated at different pHs. The
formation of TL-AMP complex significantly improved the dissolution rate as well
as the extent of drug release at acidic pHs, while the dissolution of untreated
TL was negligible at pH 1.2 and 4.0. TL-AMP complex also achieved faster drug
release than untreated drug (about 90 vs 30 % within 30 min) at pH 6.8. After
oral administration to rats, TL-AMP complex enhanced significantly (p < 0.05)
oral drug exposure and increased Cmax and AUC by six- and threefolds,
respectively, compared to untreated TL. In conclusion, TL-AMP complex may be
promising to improve the pH-dependent dissolution as well as bioavailability of
TL.
PMID- 25119995
TI - Identification of significant features by the Global Mean Rank test.
AB - With the introduction of omics-technologies such as transcriptomics and
proteomics, numerous methods for the reliable identification of significantly
regulated features (genes, proteins, etc.) have been developed. Experimental
practice requires these tests to successfully deal with conditions such as small
numbers of replicates, missing values, non-normally distributed expression
levels, and non-identical distributions of features. With the MeanRank test we
aimed at developing a test that performs robustly under these conditions, while
favorably scaling with the number of replicates. The test proposed here is a
global one-sample location test, which is based on the mean ranks across
replicates, and internally estimates and controls the false discovery rate.
Furthermore, missing data is accounted for without the need of imputation. In
extensive simulations comparing MeanRank to other frequently used methods, we
found that it performs well with small and large numbers of replicates, feature
dependent variance between replicates, and variable regulation across features on
simulation data and a recent two-color microarray spike-in dataset. The tests
were then used to identify significant changes in the phosphoproteomes of cancer
cells induced by the kinase inhibitors erlotinib and 3-MB-PP1 in two
independently published mass spectrometry-based studies. MeanRank outperformed
the other global rank-based methods applied in this study. Compared to the
popular Significance Analysis of Microarrays and Linear Models for Microarray
methods, MeanRank performed similar or better. Furthermore, MeanRank exhibits
more consistent behavior regarding the degree of regulation and is robust against
the choice of preprocessing methods. MeanRank does not require any imputation of
missing values, is easy to understand, and yields results that are easy to
interpret. The software implementing the algorithm is freely available for
academic and commercial use.
PMID- 25119996
TI - Rising CO2 levels will intensify phytoplankton blooms in eutrophic and
hypertrophic lakes.
AB - Harmful algal blooms threaten the water quality of many eutrophic and
hypertrophic lakes and cause severe ecological and economic damage worldwide.
Dense blooms often deplete the dissolved CO2 concentration and raise pH. Yet,
quantitative prediction of the feedbacks between phytoplankton growth, CO2
drawdown and the inorganic carbon chemistry of aquatic ecosystems has received
surprisingly little attention. Here, we develop a mathematical model to predict
dynamic changes in dissolved inorganic carbon (DIC), pH and alkalinity during
phytoplankton bloom development. We tested the model in chemostat experiments
with the freshwater cyanobacterium Microcystis aeruginosa at different CO2
levels. The experiments showed that dense blooms sequestered large amounts of
atmospheric CO2, not only by their own biomass production but also by inducing a
high pH and alkalinity that enhanced the capacity for DIC storage in the system.
We used the model to explore how phytoplankton blooms of eutrophic waters will
respond to rising CO2 levels. The model predicts that (1) dense phytoplankton
blooms in low- and moderately alkaline waters can deplete the dissolved CO2
concentration to limiting levels and raise the pH over a relatively wide range of
atmospheric CO2 conditions, (2) rising atmospheric CO2 levels will enhance
phytoplankton blooms in low- and moderately alkaline waters with high nutrient
loads, and (3) above some threshold, rising atmospheric CO2 will alleviate
phytoplankton blooms from carbon limitation, resulting in less intense CO2
depletion and a lesser increase in pH. Sensitivity analysis indicated that the
model predictions were qualitatively robust. Quantitatively, the predictions were
sensitive to variation in lake depth, DIC input and CO2 gas transfer across the
air-water interface, but relatively robust to variation in the carbon uptake
mechanisms of phytoplankton. In total, these findings warn that rising CO2 levels
may result in a marked intensification of phytoplankton blooms in eutrophic and
hypertrophic waters.
PMID- 25119997
TI - Hemispheric asymmetry in the auditory facilitation effect in dual-stream rapid
serial visual presentation tasks.
AB - Even though auditory stimuli do not directly convey information related to visual
stimuli, they often improve visual detection and identification performance.
Auditory stimuli often alter visual perception depending on the reliability of
the sensory input, with visual and auditory information reciprocally compensating
for ambiguity in the other sensory domain. Perceptual processing is characterized
by hemispheric asymmetry. While the left hemisphere is more involved in
linguistic processing, the right hemisphere dominates spatial processing. In this
context, we hypothesized that an auditory facilitation effect in the right visual
field for the target identification task, and a similar effect would be observed
in the left visual field for the target localization task. In the present study,
we conducted target identification and localization tasks using a dual-stream
rapid serial visual presentation. When two targets are embedded in a rapid serial
visual presentation stream, the target detection or discrimination performance
for the second target is generally lower than for the first target; this deficit
is well known as attentional blink. Our results indicate that auditory stimuli
improved target identification performance for the second target within the
stream when visual stimuli were presented in the right, but not the left visual
field. In contrast, auditory stimuli improved second target localization
performance when visual stimuli were presented in the left visual field. An
auditory facilitation effect was observed in perceptual processing, depending on
the hemispheric specialization. Our results demonstrate a dissociation between
the lateral visual hemifield in which a stimulus is projected and the kind of
visual judgment that may benefit from the presentation of an auditory cue.
PMID- 25119998
TI - The 5 kDa protein NdhP is essential for stable NDH-1L assembly in
Thermosynechococcus elongatus.
AB - The cyanobacterial NADPH:plastoquinone oxidoreductase complex (NDH-1), that is
related to Complex I of eubacteria and mitochondria, plays a pivotal role in
respiration as well as in cyclic electron transfer (CET) around PSI and is
involved in a unique carbon concentration mechanism (CCM). Despite many
achievements in the past, the complex protein composition and the specific
function of many subunits of the different NDH-1 species remain elusive. We have
recently discovered in a NDH-1 preparation from Thermosynechococcus elongatus two
novel single transmembrane peptides (NdhP, NdhQ) with molecular weights below 5
kDa. Here we show that NdhP is a unique component of the ~ 450 kDa NDH-1L
complex, that is involved in respiration and CET at high CO2 concentration, and
not detectable in the NDH-1MS and NDH-1MS' complexes that play a role in carbon
concentration. C-terminal fusion of NdhP with his-tagged superfolder GFP and the
subsequent analysis of the purified complex by electron microscopy and single
particle averaging revealed its localization in the NDH-1L specific distal unit
of the NDH-1 complex, that is formed by the subunits NdhD1 and NdhF1. Moreover,
NdhP is essential for NDH-1L formation, as this type of NDH-1 was not detectable
in a DeltandhP::Km mutant.
PMID- 25119999
TI - Modelling size structured food webs using a modified niche model with two
predator traits.
AB - The structure of food webs is frequently described using phenomenological
stochastic models. A prominent example, the niche model, was found to produce
artificial food webs resembling real food webs according to a range of summary
statistics. However, the size structure of food webs generated by the niche model
and real food webs has not yet been rigorously compared. To fill this void, I use
a body mass based version of the niche model and compare prey-predator body mass
allometry and predator-prey body mass ratios predicted by the model to empirical
data. The results show that the model predicts weaker size structure than
observed in many real food webs. I introduce a modified version of the niche
model which allows to control the strength of size-dependence of predator-prey
links. In this model, optimal prey body mass depends allometrically on predator
body mass and on a second trait, such as foraging mode. These empirically
motivated extensions of the model allow to represent size structure of real food
webs realistically and can be used to generate artificial food webs varying in
several aspects of size structure in a controlled way. Hence, by explicitly
including the role of species traits, this model provides new opportunities for
simulating the consequences of size structure for food web dynamics and
stability.
PMID- 25120000
TI - RNAseq analysis of cassava reveals similar plant responses upon infection with
pathogenic and non-pathogenic strains of Xanthomonas axonopodis pv. manihotis.
AB - KEY MESSAGE: An RNAseq-based analysis of the cassava plants inoculated with Xam
allowed the identification of transcriptional upregulation of genes involved in
jasmonate metabolism, phenylpropanoid biosynthesis and putative targets for a
TALE. Cassava bacterial blight, a disease caused by the gram-negative bacterium
Xanthomonas axonopodis pv. manihotis (Xam), is a major limitation to cassava
production worldwide and especially in developing countries. The molecular
mechanisms underlying cassava susceptibility to Xam are currently unknown. To
identify host genes and pathways leading to plant susceptibility, we analyzed the
transcriptomic responses occurring in cassava plants challenged with either the
non-pathogenic Xam strain ORST4, or strain ORST4(TALE1 Xam ) which is pathogenic
due to the major virulence transcription activator like effector TALE1 Xam . Both
strains triggered similar responses, i.e., induction of genes related to
photosynthesis and phenylpropanoid biosynthesis, and repression of genes related
to jasmonic acid signaling. Finally, to search for TALE1 Xam virulence targets,
we scanned the list of cassava genes induced upon inoculation of ORST4(TALE1 Xam
) for candidates harboring a predicted TALE1 Xam effector binding element in
their promoter. Among the six genes identified as potential candidate targets of
TALE1 Xam a gene coding for a heat shock transcription factor stands out as the
best candidate based on their induction in presence of TALE1 Xam and contain a
sequence putatively recognized by TALE1 Xam .
PMID- 25120002
TI - Epidermal stem cells in the isthmus/infundibulum influence hair shaft
differentiation: evidence from targeted DLX3 deletion.
PMID- 25120001
TI - Knockdown of the 7S globulin subunits shifts distribution of nitrogen sources to
the residual protein fraction in transgenic soybean seeds.
AB - KEY MESSAGE: A platform of gene silencing by amiRNA had been established in
fertile transgenic soybean. We demonstrated that knockdown of storage protein
shifted the distribution of nitrogen sources in soybean seeds. Artificial
microRNAs (amiRNAs) were designed using the precursor sequence of the endogenous
soybean (Glycine max L. Merrill) miRNA gma-miR159a and expressed in transgenic
soybean plants to suppress the biosynthesis of 7S globulin, which is one of the
major storage proteins. Seed-specific expression of these amiRNAs (amiR-7S)
resulted in a strong suppression of 7S globulin subunit genes and decreased
accumulation of the 7S globulin subunits in seeds. Thus, the results demonstrate
that a platform for gene silencing by amiRNA was first developed in fertile
transgenic soybean plants. There was no difference in nitrogen, carbon, and lipid
contents between amiR-7S and control seeds. Four protein fractions were collected
from defatted mature seeds on the basis of solubility at different pH to examine
the distribution of nitrogen sources and compensatory effects. In the whey and
lipophilic fractions, nitrogen content was similar in amiR-7S and control seeds.
Nitrogen content was significantly decreased in the major soluble protein
fraction and increased in the residual fraction (okara) of the amiR-7S seeds.
Amino acid analysis revealed that increased nitrogen compounds in okara were
proteins or peptides rather than free amino acids. Our study indicates that the
decrease in 7S globulin subunits shifts the distribution of nitrogen sources to
okara in transgenic soybean seeds.
PMID- 25120005
TI - Immunogenicity of biotherapy used in psoriasis: the science behind the scenes.
AB - A potential limitation in the use of biologic drugs used to treat psoriasis is
the development of anti-drug antibodies (ADAs). Many factors contribute to this
unwanted immune response, from the product itself, to its mode of administration,
the underlying disease, and patient characteristics. ADAs may decrease the
efficacy of biologic drugs by neutralizing them or modifying their clearance and
may account for hypersensitivity reactions. This article reviews the scientific
basis of immunogenicity and the mechanisms by which it affects clinical outcomes.
It also considers testing for immunogenicity and how biologic therapy of
psoriasis may be tailored on the basis of immunogenicity.
PMID- 25120007
TI - Biophysical characterisation of calumenin as a charged F508del-CFTR folding
modulator.
AB - The cystic fibrosis transmembrane regulator (CFTR) is a cyclic-AMP dependent
chloride channel expressed at the apical surface of epithelial cells lining
various organs such as the respiratory tract. Defective processing and
functioning of this protein caused by mutations in the CFTR gene results in loss
of ionic balance, defective mucus clearance, increased proliferation of biofilms
and inflammation of human airways observed in cystic fibrosis (CF) patients. The
process by which CFTR folds and matures under the influence of various chaperones
in the secretory pathway remains incompletely understood. Recently, calumenin, a
secretory protein, belonging to the CREC family of low affinity calcium binding
proteins has been identified as a putative CFTR chaperone whose biophysical
properties and functions remain uncharacterized. We compared hydropathy,
instability, charge, unfoldability, disorder and aggregation propensity of
calumenin and other CREC family members with CFTR associated chaperones and
calcium binding proteins, wild-type and mutant CFTR proteins and intrinsically
disordered proteins (IDPs). We observed that calumenin, along with other CREC
proteins, was significantly more charged and less folded compared to CFTR
associated chaperones. Moreover like IDPs, calumenin and other CREC proteins were
found to be less hydrophobic and aggregation prone. Phylogenetic analysis
revealed a close link between calumenin and other CREC proteins indicating how
evolution might have shaped their similar biophysical properties. Experimentally,
calumenin was observed to significantly reduce F508del-CFTR aggregation in a
manner similar to AavLEA1, a well-characterized IDP. Fluorescence microscopy
based imaging analysis also revealed altered trafficking of calumenin in
bronchial cells expressing F508del-CFTR, indicating its direct role in the
pathophysiology of CF. In conclusion, calumenin is characterized as a charged
protein exhibiting close similarity with IDPs and is hypothesized to regulate
F508del-CFTR folding by electrostatic effects. This work provides useful insights
for designing optimized synthetic structural correctors of CFTR mutant proteins
in the future.
PMID- 25120009
TI - Baseline patient characteristics, incidence of CINV, and physician perception of
CINV incidence following moderately and highly emetogenic chemotherapy in Asia
Pacific countries.
AB - PURPOSE: This paper describes the incidence of chemotherapy-induced nausea and
vomiting (CINV) after highly or moderately emetogenic chemotherapy (HEC or MEC)
for cancer in six Asia Pacific countries. METHODS: Sequential adult patients
naive to chemotherapy and scheduled to receive at least two cycles of single-day
HEC or MEC were enrolled in this prospective observational study. Patients
completed the Multinational Association of Supportive Care in Cancer (MASCC)
Antiemesis Tool on post-chemotherapy days 2 and 6 to record acute-phase (first 24
h) and delayed-phase (days 2-5) CINV. RESULTS: There were 648 evaluable patients
(318 HEC, 330 MEC) from Australia (n = 74), China (153), India (88), Singapore
(57), South Korea (151), and Taiwan (125). Mean (SD) patient age was 56 (12) and
58% of patients were women; the most common primary cancers were breast (27%),
lung (22%), and colon (20%). Overall in cycle 1, complete response (no emesis or
rescue antiemetics) was recorded by 69% (95% confidence interval (CI), 66-73) of
all evaluable patients, with country percentages ranging from 55 to 78% (p <
0.001). After HEC, no emesis was recorded by 75% and no nausea by 38% of
patients. After MEC, 80% had no emesis and 50% no nausea. Acute-phase CINV was
better controlled than delayed-phase CINV, and the control of nausea was the
lowest of any CINV measure in all phases. In a CINV perception survey, physicians
tended to overestimate emesis rate and underestimate nausea rate. CONCLUSIONS:
CINV remains a substantial problem, and country-specific information about CINV
can be useful in developing strategies to improve outcomes for patients
undergoing chemotherapy.
PMID- 25120008
TI - Research in cancer care disparities in countries with universal healthcare:
mapping the field and its conceptual contours.
AB - The paper reviews published studies focused on disparities in receipt of cancer
treatments and supportive care services in countries where cancer care is free at
the point of access. We map these studies in terms of the equity stratifiers they
examined, the countries in which they took place, and the care settings and
cancer populations they investigated. Based on this map, we reflect on patterns
of scholarly attention to equity and disparity in cancer care. We then consider
conceptual challenges and opportunities in the field, including how treatment
disparities are defined, how equity stratifiers are defined and conceptualized
and how disparities are explained, with special attention to the challenge of
psychosocial explanations.
PMID- 25120010
TI - Distress among caregivers of phase I trial participants: a cross-sectional study.
AB - PURPOSE: The number of patients with cancer enrolling in phase I trials is
expected to increase as these trials incorporate patient selection and exhibit
greater efficacy in the era of targeted therapies. Despite the fact that people
with advanced cancer often require a caregiver, little is known about the
experience of caregivers of people enrolling in oncology phase I clinical trials.
We conducted a cross-sectional study assessing the distress and emotion
regulation of caregivers of phase I trial participants to inform the design of
future interventions targeting the unique needs of this population. METHODS:
Caregivers of oncology patients were approached at the patient's phase I clinical
trial screening visit. Caregiver participants completed a one-time survey
incorporating validated instruments to comprehensively assess distress and
emotion regulation. Basic demographic information about both the caregiver and
patient was collected. RESULTS: Caregivers exhibited greater distress than
population norms. Emotion regulation was also moderately impaired. Respondents
identified positive aspects of caregiving despite exhibiting moderate distress.
CONCLUSION: Enrollment of a patient in a phase I clinical trial is a time of
stress for their caregivers. This pilot study demonstrates the feasibility of
engaging caregivers of phase I trial participants and the need to better support
them through this component of their caregiving experience.
PMID- 25120011
TI - Reproductive health and endocrine disruption in women with breast cancer: a pilot
study.
AB - PURPOSE: The purpose of this study was to assess whether incorporation of an
original reproductive health assessment and algorithm into breast cancer care
helps providers appropriately manage patient reproductive health goals and to
follow laboratory markers for fertility and correlate these with menstruation.
METHODS: This prospective observational pilot study was set in an urban, public
hospital. Newly diagnosed premenopausal breast cancer patients between 18 and 49
years old were recruited for this study prior to chemotherapy initiation. As the
intervention, these patients received a reproductive health assessment and care
per the study algorithm at 3-month intervals for 24 months. Blood samples were
also collected at the same time intervals. The main outcome measures were to
assess if the reproductive health management was consistent with patient goals
and to track any follicle-stimulating hormone (FSH) and thyroid-stimulating
hormone (TSH) level changes throughout treatment and post-treatment period.
RESULTS: Two patients were pregnant at study initiation. They received obstetric
consultations, opted to continue pregnancies, and postpone treatment; both
delivered at term without complications. One woman desired future childbearing
and received fertility preservation counseling. All women received family
planning consultations and received/continued effective contraceptive methods.
Seventy-three percent used long-term contraception, 18 % remained abstinent, and
9 % used condoms. During chemotherapy, FSH rose to menopausal levels in 82 % of
patients and TSH rose significantly in 9 %. While 82 % of women experienced
amenorrhea, 44 % of these women resumed menstruation after chemotherapy.
CONCLUSIONS: The assessment and algorithm were useful in managing patients'
reproductive health needs. Chemotherapy-induced endocrine disruption impacted
reproductive health.
PMID- 25120012
TI - Peripherally inserted central catheters in non-hospitalized cancer patients: 5
year results of a prospective study.
AB - PURPOSE: Few prospective follow-up studies evaluating the use of peripherally
inserted central catheters (PICCs) to deliver chemotherapy and/or home parenteral
nutrition (HPN) have focused exclusively on oncology outpatients. The aim of this
prospective study was to assess the reliability and the safety of PICCs over a 5
year use in non-hospitalized cancer patients requiring long-term intravenous
therapies. METHODS: Since June 2008, all adult oncology outpatient candidates for
PICC insertion were consecutively enrolled and the incidence of catheter-related
complications was investigated. The follow-up continued until the PICC removal.
RESULTS: Two hundred sixty-nine PICCs in 250 patients (98 % with solid
malignancies) were studied, for a total of 55,293 catheter days (median dwell
time 184 days, range 15-1,384). All patients received HPN and 71 % received
chemotherapy during the study period. The incidence of catheter-related
bloodstream infections (CRBSIs) was low (0.05 per 1,000 catheter days), PICC
related symptomatic thrombosis was rare (1.1 %; 0.05 per 1,000 catheter days),
and mechanical complications were uncommon (13.1 %; 0.63 per 1,000 catheter
days). The overall complication rate was 17.5 % (0.85 per 1,000 catheter days)
and PICCs were removed because of complications only in 7 % of cases. The main
findings of this study were that, if accurately managed, PICCs can be safely used
in cancer patients receiving chemotherapy and/or HPN, recording a low incidence
of CRBSI, thrombosis, and mechanical complications; a long catheter life span;
and a low probability of catheter removal because of complications. CONCLUSIONS:
Our study suggests that PICCs can be successfully utilized as safe and long
lasting venous access devices in non-hospitalized cancer patients.
PMID- 25120013
TI - Is there coronary artery disease in the cancer patient who manifests with chest
pain, shortness of breath and/or tachycardia? A retrospective observational
cohort.
AB - OBJECTIVE: Cancer therapies lead to chest pain (CP), shortness of breath (SOB),
and/or tachydysrhythmias (TACH Y) requiring cardiac risk stratification including
coronary computed tomographic angiography (CCTA). We posit that cancer patients
with CP, SOB and/or TACH Y have greater odds of having coronary artery disease
(CAD) identified by CCTA than those that do not. METHODS: Eligibility for this
IRB-approved retrospective observational cohort included those with cancer that
had CCTA performed. Groups were stratified with and without CP, SOB, and/or TACH
Y. Electronic medical records were mined for appropriate CPT codes from 01012010
to 08312013. Demographics, cancer type, and clinical outcomes were obtained.
Standard t tests, odds ratios, and frequencies were used. RESULTS: Of 176
participants identified; 84 were male (48 %) and 118 were Caucasian (67 %). Of
those, 100/176 (57 %) had CP, SOB, and/or TACH Y; 72/100 (72 %) had CP; 10/100
(10 %) had TACH Y; and 18/100 (18 %) had SOB. Of the 72 with CP, 40 (56 %) had
CAD; of the 10 with TACH Y, 6 (60 %) had CAD; of the 18 with SOB, and 10 (56 %)
had CAD. Thus, a 2.6-fold increased odds of having CAD (56/100 = 56 %) compared
to 25/76 (33 %) in the group with cancer without CP, SOB, and/or TACH Y (95 % CI
= 1.40 to 4.83; p = 0.003). CONCLUSION: Cancer patients with CP, SOB, and/or TACH
Y have a 2.6-fold increased odds of having CAD compared to cancer patients
without CP, SOB, and/or TACH Y (95 % CI = 1.40 to 4.83; p = 0.003).
PMID- 25120015
TI - Antiplatelet therapy in the management of myeloproliferative neoplasms.
AB - Low-dose acetylsalicylic acid (ASA) is given to most patients with polycythemia
vera (PV) and essential thrombocythemia (ET) although some uncertainties
encompass this clinical practice. In patients with history of thrombosis, the use
of ASA is supported on the results observed in the general population showing a
substantial net benefit of this treatment in preventing thrombosis. In the
European collaboration study on low-dose aspirin in polycythemia vera (ECLAP),
ASA reduced the risk of thrombosis without increasing the risk of major bleeding
when compared with placebo, supporting the primary prevention of thrombosis in
PV. In ET, the efficacy of low-dose ASA has not been tested in randomized
clinical trials. Two retrospective studies have shown that low-dose ASA could
benefit ET patients older than 60 years when combined with cytoreduction, whereas
in young, low-risk patients, ASA benefits to particular subgroups of patients. In
spite of the fact that in primary myelofibrosis the incidence of thrombosis is
increased, the use of ASA is not clearly recommended.
PMID- 25120014
TI - Exploring the relation of harsh parental discipline with child emotional and
behavioral problems by using multiple informants. The generation R study.
AB - Parental harsh disciplining, like corporal punishment, has consistently been
associated with adverse mental health outcomes in children. It remains a
challenge to accurately assess the consequences of harsh discipline, as
researchers and clinicians generally rely on parent report of young children's
problem behaviors. If parents rate their parenting styles and their child's
behavior this may bias results. The use of child self-report on problem behaviors
is not common but may provide extra information about the relation of harsh
parental discipline and problem behavior. We examined the independent
contribution of young children's self-report above parental report of emotional
and behavioral problems in a study of maternal and paternal harsh discipline in a
birth cohort. Maternal and paternal harsh discipline predicted both parent
reported behavioral and parent reported emotional problems, but only child
reported behavioral problems. Associations were not explained by pre-existing
behavioral problems at age 3. Importantly, the association with child reported
outcomes was independent from parent reported problem behavior. These results
suggest that young children's self-reports of behavioral problems provide unique
information on the effects of harsh parental discipline. Inclusion of child self
reports can therefore help estimate the effects of harsh parental discipline more
accurately.
PMID- 25120018
TI - Size effects in bimagnetic CoO/CoFe2O4 core/shell nanoparticles.
AB - The control of the size of bimagnetic nanoparticles represents an important step
toward the study of fundamental properties and the design of new nanostructured
magnetic materials. We report the synthesis and the structural and magnetic
characterization of bimagnetic CoO/CoFe2O4 core/shell nanoparticles. The material
was fabricated by a seed-mediated growth high-temperature decomposition method
with sizes in the range of 5-11 nm. We show that the core/shell morphology
favours the crystallinity of the shell phase, and the reduction of the particle
size leads to a remarkable increase of the magnetic hardening. When the size is
reduced, the coercive field at 5 K increases from 21.5 kOe to 30.8 kOe, while the
blocking temperature decreases from 388 K to 167 K. The size effects on the
magnetic behaviour are described through a phenomenological model for strongly
ferri-/antiferromagnetic coupled phases.
PMID- 25120016
TI - Functional and psychosocial impact of oral disorders and quality of life of
people living with HIV/AIDS.
AB - PURPOSE: This study compared the Quality of Life (QOL) according to the presence
of functional and psychosocial impact of oral disorders and evaluated the
convergent validity between the dimensions of the WHOQOL and the OHIP-14 scores
among people living with HIV. METHODS: This was a cross-sectional study with
patients enrolled in reference centres of a midsize Brazilian city. Interviews
were conducted when the participants arrived at the centres seeking services for
medical appointments and collecting medicines. The OHIP-14 was used to evaluate
the functional and psychosocial impact of oral disorders. QOL was assessed using
the general issues and six domains of the WHOQOL-HIV BREF. The Chi square test,
Mann-Whitney test, and Spearman correlation analysis were used for analysis.
RESULTS: The sample comprised 422 people living with HIV/AIDS (response rate:
81.2%). The prevalence of functional and psychosocial impact of oral disorders
was 34.0%. The prevalence of very poor/poor QOL and those who were very
dissatisfied/dissatisfied with their health was higher among those with
functional and psychosocial impact of oral disorders. There was a negative
correlation between the scores on the domains of QOL and the severity of the
impact of the oral disorders (r-value ranged from -0.107 to -0.30). CONCLUSION:
Individuals with functional and psychosocial impact of oral disorders were found
to more frequently rate their QOL as poor/very poor, and were more often
dissatisfied with health. The correlation between the scores of QOL and
functional and psychosocial impact of oral disorders scores was weak, indicating
that they represent different constructs. The measures of functional and
psychosocial impact of oral disorders should be complemented by general measures
of QOL.
PMID- 25120019
TI - Fibroelastolytic papulosis in an elderly woman with a 30-year history:
overlapping between pseudoxanthoma elasticum-like papillary dermal elastolysis
and white fibrous papulosis of the neck.
PMID- 25120017
TI - Quality of life after pulmonary embolism: first cross-cultural evaluation of the
pulmonary embolism quality-of-life (PEmb-QoL) questionnaire in a Norwegian
cohort.
AB - PURPOSE: The aim of the current study was to translate and test the
psychometrical properties of the disease-specific pulmonary embolism quality-of
life questionnaire (PEmb-QoL). METHODS: Patients with a prior history of
pulmonary embolism (PE) were identified from the thrombosis registry at Ostfold
Hospital Trust, Fredrikstad, Norway. All eligible patients were asked to complete
the generic EuroQol 5-dimension (EQ-5D) QoL questionnaire as well as the disease
specific PEmb-QoL at baseline and after 2 weeks. Construct validity was tested
using principal component factor analysis. Criterion validity was tested using
Spearman's correlation coefficients (rho) between EQ-5D and PEmb-QoL. Internal
consistency reliability was calculated using Cronbach's alpha coefficient, while
test-retest reliability was calculated using the intra-class correlation
coefficients (ICC). RESULTS: A total of 213 participants had complete datasets
and were included in further analyses. Factor analysis with varimax rotation
yielded six factors explaining 71% of the cumulative variance. Cronbach's alpha
coefficient was found to be 0.94, indicating a very good intercorrelation of
items. Of the 213 participants, 145 (68%) completed the questionnaire a second
time. The ICC ranged from 0.75 to 0.86, indicating good test-retest reliability.
All factors were found significant with p values <0.001. The criterion validity
of the PEmb-QoL was confirmed through good correlation with other similar health
related quality-of-life constructs in the EQ-5D. CONCLUSIONS: Findings of the
current study indicate that Norwegian version of the PEmb-QoL is both valid and
reliable, thus representing an important supplement in subjective outcomes
measurement among patients sustaining PE.
PMID- 25120021
TI - Cellular transplantation-based evolving treatment options in spinal cord injury.
AB - Spinal cord injury (SCI) often represents a condition of permanent neurologic
deficit. It has been possible to understand and delineate the mechanisms
contributing to loss of function following primary injury. The clinicians might
hope to improve the outcome in SCI injury by designing treatment strategies that
could target these secondary mechanisms of response to injury. However, the
approaches like molecular targeting of the neurons or surgical interventions have
yielded very limited success till date. In recent times, a great thrust is put on
to the cellular transplantation mode of treatment strategies to combat SCI
problems so as to gain maximum functional recovery. In this review, we discuss
about the various cellular transplantation strategies that could be employed in
the treatment of SCI. The success of such cellular approaches involving Schwann
cells, olfactory ensheathing cells, peripheral nerve, embryonic CNS tissue and
activated macrophage has been supported by a number of reports and has been
detailed here. Many of these cell transplantation strategies have reached the
clinical trial stages. Also, the evolving field of stem cell therapy has made it
possible to contemplate the role of both embryonic stem cells and induced
pluripotent stem cells to stimulate the differentiation of neurons when
transplanted in SCI models. Moreover, the roles of tissue engineering techniques
and synthetic biomaterials have also been explained with their beneficial and
deleterious effects. Many of these cell-based therapeutic approaches have been
able to cause only a little change in recovery and a combinatorial approach
involving more than one strategy are now being tried out to successfully treat
SCI and improve functional recovery.
PMID- 25120020
TI - Species distribution of clinical Acinetobacter isolates revealed by different
identification techniques.
AB - A total of 2582 non-duplicate clinical Acinetobacter spp. isolates were collected
to evaluate the performance of four identification methods because it is
important to identify Acinetobacter spp. accurately and survey the species
distribution to determine the appropriate antimicrobial treatment. Phenotyping
(VITEK 2 and VITEK MS) and genotyping (16S rRNA and rpoB gene sequencing) methods
were applied for species identification, and antimicrobial susceptibility test of
imipenem and meropenem was performed with a disk diffusion assay. Generally, the
phenotypic identification results were quite different from the genotyping
results, and their discrimination ability was unsatisfactory, whereas 16S rRNA
and rpoB gene sequencing showed consistent typing results, with different
resolution. Additionally, A. pittii, A. calcoaceticus and A. nosocomialis, which
were phylogenetically close to A. baumannii, accounted for 85.5% of the non-A.
baumannii isolates. One group, which could not be clustered with any reference
strains, consisted of 11 isolates and constituted a novel Acinetobacter species
that was entitled genomic species 33YU. None of the non-A. baumannii isolates
harbored a blaOXA-51-like gene, and this gene was disrupted by ISAba19 in only
one isolate; it continues to be appropriate as a genetic marker for A. baumannii
identification. The resistance rate of non-A. baumannii isolates to imipenem
and/or meropenem was only 2.6%, which was significantly lower than that of A.
baumannii. Overall, rpoB gene sequencing was the most accurate identification
method for Acinetobacter species. Except for A. baumannii, the most frequently
isolated species from the nosocomial setting were A. pittii, A. calcoaceticus and
A. nosocomialis.
PMID- 25120022
TI - Dosage effect of rocuronium on intraoperative neuromonitoring in patients
undergoing thyroid surgery.
AB - The effect of different concentrations of rocuronium bromide used for anesthesia
induction during thyroid surgery on the intraoperative recurrent laryngeal nerve
monitoring was evaluated. One hundred patients undergoing thyroid operation were
randomized into five groups (20 patients per group). Patients in group I were
operated and monitored without the use of rocuronium bromide. Patients in groups
II-V were respectively injected with 0.5x, 1x, 1.5x, and 2x ED95 rocuronium
bromide intravenously. The time from injecting the rocuronium bromide to the
beginning of tube insertion was recorded, the conditions of tracheal intubation
were evaluated, and the changes in blood pressure and pulse during the intubation
process were monitored. Vagus nerve/recurrent laryngeal nerve evoked muscle
potential was monitored using the NIM-Response3.0 nerve electromyography monitor.
The amplitude of electromyography signal was recorded every 5 min during 30 min
after successful tracheal intubation. The tracheal intubation success rate was
100% in all groups. Compared with group I, intubating condition scores (Cooper
scores) in the patients of groups II-V were higher (P < 0.05). The stability of
intraoperative neuromonitoring signal amplitude in groups I-III met the
monitoring standards. The findings suggest that the use of 0.5x or 1x ED95
rocuronium bromide during the anesthesia induction can improve the tracheal tube
conditions without affecting the intraoperative recurrent laryngeal nerve
monitoring. The use of 1x ED95 rocuronium bromide induction was associated with
the best results.
PMID- 25120023
TI - High-level S100A6 promotes metastasis and predicts the outcome of T1-T2 stage in
clear cell renal cell carcinoma.
AB - S100A6 (calcyclin), functions in cell cycle progression and differentiation, has
been reported to promote the tumorigenesis and malignancy of many types of
cancers. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of
RCC, lacking both promising prognostic markers and effective therapeutic targets.
In our previous study, we have found the elevated S100A6 in the ccRCC tumor
tissues, and the differentially expressed genes determined by microarray analysis
were found to be strongly related to tumor metastasis after S100A6 knockdown and
overexpression in the ccRCC cell line 786-O. The mRNA expression of S100A6
detected by RT-PCR in 6 cell lines and 174 tumor tissues, including 58 metastatic
ccRCC and 116 clinicopathological features paired non-metastatic ccRCC (1:2),
indicated S100A6 was elevated in the metastatic cells and tumor tissues. The
protein expression was consistent with mRNA expression. The biological function
of S100A6 in promoting metastasis was determined through overexpression and
knockdown of S100A6 in the ccRCC cell lines 786-O, caki-1, and ACHN. In the
scratch wound migration assay as well as migration and invasion assays, S100A6
knockdown significantly suppressed the migratory and invasive abilities of tumor
cells, whereas overexpression enhanced the malignancy. Further research with the
follow-up data of 129 ccRCC patients were analyzed by the Cox regression and
survival analysis. The expression of S100A6 was up-regulated in metastatic ccRCC
cells. In the metastatic tumor tissues, the expression of S100A6 was also higher
than in the non-metastatic tissues. High S100A6 expression might be crucial to
promote metastasis in ccRCC by enhancing the ability of tumor cells migration and
invasion. In addition, the quantitative mRNA expression of S100A6 in the tumor
tissues was an independent risk factor and might be used as a prognostic marker
for the metastatic risk of the localized T1-T2 stage ccRCC.
PMID- 25120025
TI - Effects of brain lesions on moral agency: ethical dilemmas in investigating moral
behavior.
AB - Understanding how the "brain produces behavior" is a guiding idea in
neuroscience. It is thus of no surprise that establishing an interrelation
between brain pathology and antisocial behavior has a long history in brain
research. However, interrelating the brain with moral agency--the ability to act
in reference to right and wrong--is tricky with respect to therapy and
rehabilitation of patients affected by brain lesions. In this contribution, we
outline the complexity of the relationship between the brain and moral behavior,
and we discuss ethical issues of the neuroscience of ethics and of its clinical
consequences. First, we introduce a theory of moral agency and apply it to the
issue of behavioral changes caused by brain lesions. Second, we present a
typology of brain lesions both with respect to their cause, their temporal
development, and the potential for neural plasticity allowing for rehabilitation.
We exemplify this scheme with case studies and outline major knowledge gaps that
are relevant for clinical practice. Third, we analyze ethical pitfalls when
trying to understand the brain-morality relation. In this way, our contribution
addresses both researchers in neuroscience of ethics and clinicians who treat
patients affected by brain lesions to better understand the complex ethical
questions, which are raised by research and therapy of brain lesion patients.
PMID- 25120024
TI - Effect of different iodine concentrations on well-differentiated thyroid cancer
cell behavior and its inner mechanism.
AB - High iodine intake might be an important factor in the promotion of thyroid
cancer and the incidence of thyroid carcinoma has increased obviously these years
especially in area of high iodine intake, though the mechanism of which remains
unknown. The aim of present study was to gain more insight into the influence of
different iodine concentrations on cell behavior, such as proliferation and
migration, and to further investigate its molecular mechanism using two well
differentiated thyroid cancer cell lines. Our study evaluated the effect of
different iodine concentrations on cell behavior and investigated relevant
molecules involved. The results indicated that iodine in vitro could promote the
growth of thyroid cancer cells with the increase of iodine concentration in a
specific range. Such effect may be related to signaling pathways as Akt and Erk
and cytokine VEGF-A.
PMID- 25120026
TI - Post-vaccinal distemper encephalitis in two Border Collie cross littermates.
AB - CASE HISTORY: One 4.5-month-old male Border Collie cross presented with
aggression and seizures in October 2006. A 16-month-old, female, spayed Border
Collie cross presented with hypersalivation and a dropped jaw and rapidly became
stuporous in September 2007. The dogs were littermates and developed acute
neurological signs 5 and 27 days, respectively, after vaccination with different
modified live vaccines containing canine distemper virus. HISTOPATHOLOGICAL
FINDINGS: Sections of brain in both dogs showed evidence of encephalitis mainly
centred on the grey matter of brainstem nuclei, where there was extensive and
intense parenchymal and perivascular infiltration of histiocytes and lymphocytes.
Intra-nuclear and intra-cytoplasmic inclusions typical of distemper were
plentiful and there was abundant labelling for canine distemper virus using
immunohistochemistry. DIAGNOSIS: Post-vaccinal canine distemper. CLINCIAL
RELEVANCE: Post-vaccinal canine distemper has mainly been attributed to virulent
vaccine virus, but it may also occur in dogs whose immunologic nature makes them
susceptible to disease induced by a modified-live vaccine virus that is safe and
protective for most dogs.
PMID- 25120027
TI - [Subacute lower back pain and acute kidney failure in a 47-year old man].
AB - A 47-year-old man presented with subacute, low back pain and increased creatinine
levels. A CT scan showed an extrinsic, bilateral compression of the ureters by a
retroperitoneal mass with pronounced uptake of 18F-fluorodeoxyglucose in positron
emission tomography. Histological findings were consistent with the diagnosis of
retroperitoneal fibrosis. Urological decompression was performed. The initiated
corticosteroids led to a rapid clinical improvement and regression of the
retroperitoneal mass. A relapse occurred after tapering of corticosteroids with a
prompt response to increase of the dosage.
PMID- 25120028
TI - Higher apolipoprotein B levels are associated with earlier onset of first-ever
atherosclerotic stroke.
AB - BACKGROUND: Many studies have revealed apolipoproteins are risk factors for
ischemic stroke, but the influence of apolipoproteins on onset age of first-ever
atherosclerotic stroke has not been well investigated. METHODS: We recruited 357
qualified participants from consecutive patients with acute ischemic stroke who
came to the stroke registry center in Sichuan Provincial People's Hospital,
Chengdu, China. Patients were stratified into tertiles according to the
distributions of apoB levels for large artery atherosclerosis (LAA) and small
artery atherosclerosis (SAA) groups. The onset age of stroke was analyzed
tripartitely in terms of early-onset group, the middling-onset group and the late
onset group. Multinomial logistical regression was used to analyze the
associations between the two. RESULTS: The risk of early-onset stroke increased
monotonically with higher apoB levels (the second tertile, adjusted OR = 2.61,
95% CI 1.18-5.79 (p = 0.018); the third tertile, adjusted OR = 19.52, 95% CI 5.93
64.31 (p < 0.001)), and patients with the highest tertile of apoB levels had a
9.20 times (95% CI, 2.97-28.53, p < 0.001) increased risk of middling-onset
stroke in reference to late onset of stroke. CONCLUSIONS: The present study
suggests the higher the apolipoprotein B levels are, the earlier an
atherosclerotic stroke might occur in a Chinese population.
PMID- 25120030
TI - Flavonoid content, free radical scavenging and increase in xanthine oxidase
inhibitory activity in Galgeun-tang following fermentation with Lactobacillus
plantarum.
AB - Galgeun-tang (GT) prior to and following fermentation with Lactobacillus
plantarum was analyzed to determine the total polyphenol and flavonoid contents
and the antioxidant activity. GT, fermented GT (FGT) and their three solvent
partitioned fractions, which were prepared by successive partitioning with ethyl
acetate (EtOAc), butanol (BuOH) and water, were evaluated for total polyphenol
and flavonoid contents, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging
activity and xanthine oxidase (XO) inhibitory activity. Following fermentation,
the total polyphenol content only increased slightly; however, the flavonoid
content increased by 24.3%. The radical scavenging activity increased from 22.4
to 27.5% and the XO inhibitory activity increased from 20.2 to 62.4% at 500
ug/ml. The EtOAc fraction among the solvent-partitioned fractions demonstrated
the highest total polyphenol and flavonoid contents, radical scavenging
activities and XO inhibitory activity, and the quantity also markedly increased
following fermentation.
PMID- 25120031
TI - Maturation of Plasmodium falciparum in multiply infected erythrocytes and the
potential role in malaria pathogenesis.
AB - Erythrocytes containing two or more parasites, referred to here as multiply
infected erythrocytes (MIEs), are common in the blood of humans infected by
Plasmodium falciparum. It is necessary to study these cells closely because the
excess numbers of parasites they contain suggest that they could be overloaded
with virulence factors. Here, microscopic examinations of blood smears from
patients showed that up to seven merozoites can successfully invade an
erythrocyte and mature to ring stage. However, in vitro culture showed that only
up to three parasites can mature to late schizont stage. These observations were
made by culturing the parasites in erythrocytes containing hemoglobin AA (HbAA),
HbAS, and HbSS. Biochemical analysis of saponin-concentrated culture suggests
that more hemozoin is produced in a MIE than in a singly infected erythrocyte
(SIE). Studies have shown that ingestion of excessive hemozoin destroys monocytes
and neutrophils, which could impair the immune system. Cultured parasites were
also examined by transmission electron microscopy, and it was found that the
quantity of knobs was dramatically increased on the membranes of erythrocytes
containing multiple schizonts, compared to those containing only one schizont.
Knobs contain, among other things, P. falciparum erythrocyte membrane protein 1
(PfEMP1) complex which mediates sequestration and promotes severe malaria. These
findings suggest that P. falciparum increases its virulence by producing MIEs. On
sexual life cycle of the parasite, microphotographs are presented in this report
showing, for the first time, that two gametocytes can develop in one erythrocyte;
they are referred to here as twin gametocytes. It is not known whether they can
infect mosquitoes.
PMID- 25120032
TI - Acute visceral cysticercosis by Taenia hydatigena in lambs and treatment with
praziquantel.
AB - An acute outbreak of Taenia hydatigena cysticercosis, causing mortality in 5 of
21 (23.8%) female lambs, is reported. Gross post-mortem examinations and
histology showed Cysticercus tenuicollis as the cause of death. Biochemical
parameters in infected lambs confirmed severe hepatitis. Praziquantel, given once
at 15 mg/kg body weight (bw), was administered and a dramatic improvement in the
clinical condition and biochemical parameters was observed up to 30 days
following treatment.
PMID- 25120029
TI - Analysis of TNF-antagonist switch over time and associated risk factors in the
Swiss Inflammatory Bowel Disease Cohort.
AB - BACKGROUND AND AIMS: Limited data from large cohorts are available on tumor
necrosis factor (TNF) antagonists (infliximab, adalimumab, certolizumab pegol)
switch over time. We aimed to evaluate the prevalence of switching from one TNF
antagonist to another and to identify associated risk factors. METHODS: Data from
the Swiss Inflammatory Bowel Diseases Cohort Study (SIBDCS) were analyzed.
RESULTS: Of 1731 patients included into the SIBDCS (956 with Crohn's disease [CD]
and 775 with ulcerative colitis [UC]), 347 CD patients (36.3%) and 129 UC
patients (16.6%) were treated with at least one TNF antagonist. A total of 53/347
(15.3%) CD patients (median disease duration 9 years) and 20/129 (15.5%) of UC
patients (median disease duration 7 years) needed to switch to a second and/or a
third TNF antagonist, respectively. Median treatment duration was longest for the
first TNF antagonist used (CD 25 months; UC 14 months), followed by the second
(CD 13 months; UC 4 months) and third TNF antagonist (CD 11 months; UC 15
months). Primary nonresponse, loss of response and side effects were the major
reasons to stop and/or switch TNF antagonist therapy. A low body mass index, a
short diagnostic delay and extraintestinal manifestations at inclusion were
identified as risk factors for a switch of the first used TNF antagonist within
24 months of its use in CD patients. CONCLUSION: Switching of the TNF antagonist
over time is a common issue. The median treatment duration with a specific TNF
antagonist is diminishing with an increasing number of TNF antagonists being
used.
PMID- 25120033
TI - Elastic properties of chemical-vapor-deposited monolayer MoS2, WS2, and their
bilayer heterostructures.
AB - Elastic properties of materials are an important factor in their integration in
applications. Chemical vapor deposited (CVD) monolayer semiconductors are
proposed as key components in industrial-scale flexible devices and building
blocks of two-dimensional (2D) van der Waals heterostructures. However, their
mechanical and elastic properties have not been fully characterized. Here we
report high 2D elastic moduli of CVD monolayer MoS2 and WS2 (~170 N/m), which is
very close to the value of exfoliated MoS2 monolayers and almost half the value
of the strongest material, graphene. The 2D moduli of their bilayer
heterostructures are lower than the sum of 2D modulus of each layer but
comparable to the corresponding bilayer homostructure, implying similar
interactions between the hetero monolayers as between homo monolayers. These
results not only provide deep insight into understanding interlayer interactions
in 2D van der Waals structures but also potentially allow engineering of their
elastic properties as desired.
PMID- 25120034
TI - BRCA genetic counseling among at-risk Latinas in New York City: new beliefs shape
new generation.
AB - Despite the life-saving information that genetic counseling can provide for women
at hereditary breast and/or ovarian cancer (HBOC) risk, Latinas
disproportionately underuse such services. Understanding Latinas' beliefs and
attitudes about BRCA genetic counseling may be the key to better health promotion
within this underserved, at-risk group. We conducted 12 focus groups (N = 54)
with at-risk Latina women in New York City, followed by 30 in-depth interviews
among a subset of the focus group women. Both were professionally transcribed,
translated where applicable and data analysis was completed by two coders trained
in qualitative methods. Results revealed personal and community knowledge about
BRCA genetic counseling was relatively low, although women felt largely positive
about counseling. The main motivator to undergo genetic counseling was concerns
about learning family members' cancer status, while the main barrier was
competing demands. Generational differences were apparent, with younger women
(approximately <55 years) reporting that they were more interested in educating
themselves about counseling and other ways to prevent cancer. Younger women were
also less likely to ascribe to traditionally Latino-centered cultural beliefs
which could serve as barriers (e.g. machismo, fatalismo, destino) to undergoing
genetic counseling. Participants were largely enthusiastic about educational
efforts to increase awareness of genetic counseling among Latinos. Revealing the
beliefs and attitudes of underserved Latinas may help shape culturally
appropriate educational materials and promotion programs to increase BRCA genetic
counseling uptake within this underrepresented community.
PMID- 25120035
TI - A pilot study of BRCA mutation carriers' knowledge about the clinical impact of
prophylactic-oophorectomy and views on fertility consultation: a single-center
pilot study.
AB - BRCA mutation carriers will experience early surgically induced menopause
following prophylactic bilateral salpingo-oophorectomy (PBSO). This pilot study
aimed to investigate their (1) knowledge about the clinical impact of PBSO; (2)
views on fertility consultation (FC)/fertility preservation (FP) treatment; and
(3) difficulties in conceiving compared to non-carriers. A cross-sectional,
single institution web-survey was performed at a university-based IVF center.
Women aged 18-50 years who were screened for BRCA gene mutations from 2005 to
2013 were recruited via mail. Forty-one BRCA-positive and 110 BRCA-negative women
completed the survey (response rate: 50 %). The knowledge about the reproductive
impact of PBSO was limited, with the majority of women in this highly educated
sample only identifying the correct response 64 % of the time. Among BRCA
mutation carriers, 24 (59 %) had positive views about FC/FP treatments. A larger
proportion of women with no children at the time of BRCA testing, and those who
were non-white tended to have positive views toward FP. Women with, versus
without, BRCA mutations were more likely to have difficulty in conceiving (p =
0.08). This well-educated group had limited knowledge about the reproductive
clinical impact of PBSO, or the benefit of a FP before PBSO. Most women with BRCA
mutations were interested in FC/FP treatment if they had not completed
childbearing at the time of screening. Targeted referrals for FC at the time of
BRCA screening may help women improve knowledge and allow improved decision
making about reproductive options.
PMID- 25120036
TI - Mothers' experiences of genetic counselling in Johannesburg, South Africa.
AB - Genetic counselling is offered in diverse settings, and patient reactions vary
due to differences in personal, family and community beliefs, local healthcare
settings, as well as cultural background. Together, these factors influence how
individuals experience genetic counselling. This study aimed to describe and
document the experiences of thirteen mothers, with children with Down syndrome,
oculocutaneous albinism or haemophilia B, who had received genetic counselling at
state hospitals in Johannesburg, South Africa. A qualitative research design
drawing on principles of Interpretative Phenomenological Analysis was used. Four
voice-recorded focus groups were conducted and the resulting data were analysed
using thematic content analysis. Five themes were identified in the data: thrown
into the unknown; a worthwhile experience; a break in communication; telling the
family and the community; and spreading the word. It was seen that genetic
counselling cannot be viewed as a singular experience, but rather as one which is
influenced by mothers' lived experiences and their interactions with other
healthcare services, family and community members. The results from this study
showed that genetic services and conditions were poorly understood, that the
experience of genetic counselling varied amongst mothers, and on-going patient
support is needed particularly when addressing family and community members.
Further research is needed to assess what information is valuable to individuals
during genetic counselling and how to deliver this information in a contextually
appropriate manner. Greater awareness of genetic conditions is also required
amongst communities and healthcare professionals. Valuable insight was gained
from this study which can be used to improve local training programmes and
genetic counselling services in Johannesburg, and in South Africa.
PMID- 25120037
TI - Clinical utility of chromosomal microarray analysis of DNA from buccal cells:
detection of mosaicism in three patients.
AB - Mosaic chromosomal abnormalities are relatively common. However, mosaicism may be
missed due to multiple factors including failure to recognize clinical
indications and order appropriate testing, technical limitations of diagnostic
assays, or sampling tissue (s) in which mosaicism is either not present, or
present at very low levels. Blood leukocytes have long been the "gold standard"
sample for cytogenetic analysis; however, the culturing process for routine
chromosome analysis can complicate detection of mosaicism since the normal cell
line may have a growth advantage in culture, or may not be present in the cells
that produce metaphases (the lymphocytes). Buccal cells are becoming increasingly
utilized for clinical analyses and are proving to have many advantages. Buccal
swabs allow for simple and noninvasive DNA collection. When coupled with a
chromosomal microarray that contains single nucleotide polymorphic probes,
analysis of buccal cells can maximize a clinician's opportunity to detect
cytogenetic mosaicism. We present three cases of improved diagnosis of mosaic
aberrations using buccal specimens for chromosomal microarray analysis. In each
case, the aberration was either undetectable in blood or present at such a low
level it likely could have gone undetected. These cases highlight the limitations
of certain laboratory methodologies for identifying mosaicism. We also present
practice implications for genetic counselors, including clinic workflow changes
and counseling approaches based on increasing use of buccal samples.
PMID- 25120039
TI - Water-displacement plethysmography: a technique for the simultaneous thermal
manipulation and measurement of whole-hand and whole-foot blood flows.
AB - The purpose of this project was to design, construct and validate water
displacement plethysmographs for the forearm, hand and foot that could clamp
segmental skin temperature whilst simultaneously measuring cutaneous blood flow.
Two experiments were performed. In the first, the forearm plethysmograph was
validated against a mercury-in-silastic plethysmograph under thermoneutral
conditions, with and without forearm heating. Cutaneous vascular conductance was
elevated almost three-fold by this treatment, however, there were no significant
differences between the two forms of plethysmography in either state (P > 0.05).
In study two, hand and foot blood flows were measured under clamped thermoneutral
conditions, but with three local skin temperature treatments (5, 25, 40 degrees
C). The hand had significantly higher blood flows than the foot at both 25
degrees C (4.07 versus 2.20 mL.100 mL( - 1).min( - 1); P < 0.05) and 40 degrees
C (8.20 versus 4.47 mL.100 mL( - 1).min( - 1); P < 0.05). The foot was maximally
constricted during the two lower temperatures, yet the cutaneous thermal
sensitivity of the hand was almost two-fold greater (P < 0.05). This evidence
supports the significant role played by these appendages in heat loss and
conservation, and these plethysmographs will now be used to map cutaneous
vascular responses (forearm, hand, calf, foot) across combinations of core and
local skin temperatures.
PMID- 25120038
TI - Use of a patient-entered family health history tool with decision support in
primary care: impact of identification of increased risk patients on genetic
counseling attendance.
AB - Several barriers inhibit collection and use of detailed family health history
(FHH) in primary care. MeTree, a computer-based FHH intake and risk assessment
tool with clinical decision support, was developed to overcome these barriers.
Here, we describe the impact of MeTree on genetic counseling (GC) referrals and
attendance. Non-adopted, English speaking adults scheduled for a well-visit in
two community-based primary-care clinics were invited to participate in an
Implementation-Effectiveness study of MeTree. Participants' demographic
characteristics and beliefs were assessed at baseline. Immediately after an
appointment with a patient for whom GC was recommended, clinicians indicated
whether they referred the patient and, if not, why. The study genetic counselor
kept a database of patients with a GC recommendation and contacted those with a
referral. Of 542 patients completing MeTree, 156 (29 %) received a GC
recommendation. Of these, 46 % (n = 72) were referred and 21 % (n = 33) underwent
counseling. Patient preferences, additional clinical information unavailable to
MeTree, and an incomplete clinician evaluation of the FHH accounted for the 85
patients clinicians chose not to refer. Although MeTree identified a significant
proportion of patients for whom GC was recommended, persistent barriers indicate
the need for improved referral processes and patient and physician education
about the benefits of GC.
PMID- 25120042
TI - Blood donation: comparing individual characteristics, attitudes, and feelings of
donors and nondonors.
AB - The shortage of blood donors and increased demand for blood is an important
health issue. Finding ways to increase donor recruitment and retention is a
priority and, thus, an important area for research. This article aims to better
understand donors and nondonors on the basis of their social responsibility,
susceptibility to interpersonal influence, involvement in and attitude towards
the blood donation issue, and their aroused feelings. The data from 345 completed
surveys were collected via a web-based, self-administered method. Mean
differences were examined and the conceptual model was tested via structural
equation modeling. The findings provide important clarification of donation and
nondonation behavior.
PMID- 25120040
TI - Non-small-cell lung cancer resectability: diagnostic value of PET/MR.
AB - PURPOSE: To assess the diagnostic performance of PET/MR in patients with non
small-cell lung cancer. METHODS: Fifty consecutive consenting patients who
underwent routine (18)F-FDG PET/CT for potentially radically treatable lung
cancer following a staging CT scan were recruited for PET/MR imaging on the same
day. Two experienced readers, unaware of the results with the other modalities,
interpreted the PET/MR images independently. Discordances were resolved in
consensus. PET/MR TNM staging was compared to surgical staging from thoracotomy
as the reference standard in 33 patients. In the remaining 17 nonsurgical
patients, TNM was determined based on histology from biopsy, imaging results (CT
and PET/CT) and follow-up. ROC curve analysis was used to assess accuracy,
sensitivity and specificity of the PET/MR in assessing the surgical resectability
of primary tumour. The kappa statistic was used to assess interobserver agreement
in the PET/MR TNM staging. Two different readers, without knowledge of the PET/MR
findings, subsequently separately reviewed the PET/CT images for TNM staging. The
generalized kappa statistic was used to determine intermodality agreement between
PET/CT and PET/MR for TNM staging. RESULTS: ROC curve analysis showed that PET/MR
had a specificity of 92.3 % and a sensitivity of 97.3 % in the determination of
resectability with an AUC of 0.95. Interobserver agreement in PET/MR reading
ranged from substantial to perfect between the two readers (Cohen's kappa 0.646 -
1) for T stage, N stage and M stage. Intermodality agreement between PET/CT and
PET/MR ranged from substantial to almost perfect for T stage, N stage and M stage
(Cohen's kappa 0.627 - 0.823). CONCLUSION: In lung cancer patients PET/MR appears
to be a robust technique for preoperative staging.
PMID- 25120041
TI - Machine learning models for the differential diagnosis of vascular parkinsonism
and Parkinson's disease using [(123)I]FP-CIT SPECT.
AB - PURPOSE: The study's objective was to develop diagnostic predictive models using
data from two commonly used [(123)I]FP-CIT SPECT assessment methods: region-of
interest (ROI) analysis and whole-brain voxel-based analysis. METHODS: We
included retrospectively 80 patients with vascular parkinsonism (VP) and 164
patients with Parkinson's disease (PD) who underwent [(123)I]FP-CIT SPECT.
Nuclear-medicine specialists evaluated the scans and calculated bilateral caudate
and putamen [(123)I]FP-CIT uptake and asymmetry indices using BRASS software.
Statistical parametric mapping (SPM) was used to compare the radioligand uptake
between the two diseases at the voxel level. Quantitative data from these two
methods, together with potential confounding factors for dopamine transporter
availability (sex, age, disease duration and severity), were used to build
predictive models following a tenfold cross-validation scheme. The performance of
logistic regression (LR), linear discriminant analysis and support vector machine
(SVM) algorithms for ROI data, and their penalized versions for SPM data
(penalized LR, penalized discriminant analysis and SVM), were assessed. RESULTS:
Significant differences were found in the ROI analysis after covariate correction
between VP and PD patients in [(123)I]FP-CIT uptake in the more affected side of
the putamen and the ipsilateral caudate. Age, disease duration and severity were
also found to be informative in feeding the statistical model. SPM localized
significant reductions in [(123)I]FP-CIT uptake in PD with respect to VP in two
specular clusters comprising areas corresponding to the left and right striatum.
The diagnostic predictive accuracy of the LR model using ROI data was 90.3 % and
of the SVM model using SPM data was 90.4 %. CONCLUSION: The predictive models
built with ROI data and SPM data from [(123)I]FP-CIT SPECT provide great
discrimination accuracy between VP and PD. External validation of these methods
is necessary to confirm their applicability across centres.
PMID- 25120043
TI - Jaypatient-induced service sabotage behavior: the issue of self-esteem of
hospital nurses.
AB - Worrying incidents exist where disgruntled nurses destroy good service quality
through sabotage behavior. Previous studies report the organizational and
environmental factors that might lead to service sabotage behaviors; here
individual differences in proclivity to service sabotage within any given
environment of managerial context are reported. The study first uses interviews
to establish typologies of difficult patients. Regression analysis and ANOVA
applied to survey data shows that low self-esteem in nurses leads to service
sabotage behavior, and that these nurses are less mature both chronologically and
emotionally, less experienced, and less educated than their more typical
counterparts.
PMID- 25120044
TI - Awareness of and attitudes toward direct-to-consumer prescription drug
advertising among young adults.
AB - This study examines awareness and knowledge of and attitudes toward direct-to
consumer (DTC) prescription drug advertising among young adults between 18 and 24
years of age. The study finds that young adults are not as aware of prescription
drug advertising as older consumers, however, they are aware of specific heavily
advertised drugs, especially those for allergy medications, birth control, and
sleep aids. Young adults hold mixed to negative views about advertising in
general, and they do not view DTC prescription drug advertising as a beneficial
source of information, nor do they believe such advertising serves to educate
consumers.
PMID- 25120045
TI - What is driving the growth in medical tourism?
AB - The current study directly surveyed consumers on their experiences and
consideration of medical tourism to test the variables thought to impact medical
tourism. The sample was deployed to qSample's international traveler panel. The
survey was completed by 68.5% of participants. Over a third of the respondents
said they had considered medical tourism; 15% had actually traveled to another
country for medical care. Dental treatment was named most often as the type of
treatment pursued in another country. Cost was mentioned most frequently as the
reason for medical tourism. Prior international travel emerged as an important
factor.
PMID- 25120046
TI - Direct-to-consumer advertising of predictive genetic tests: a health belief model
based examination of consumer response.
AB - Direct-to-consumer (DTC) advertising of predictive genetic tests (PGTs) has added
a new dimension to health advertising. This study used an online survey based on
the health belief model framework to examine and more fully understand consumers'
responses and behavioral intentions in response to a PGT DTC advertisement.
Overall, consumers reported moderate intentions to talk with their doctor and
seek more information about PGTs after advertisement exposure, though consumers
did not seem ready to take the advertised test or engage in active information
search. Those who perceived greater threat from the disease, however, had
significantly greater behavioral intentions and information search behavior.
PMID- 25120047
TI - Attitudes and beliefs regarding direct-to-consumer advertising of pharmaceutical
drugs: an exploratory comparison of physicians and pharmaceutical sales
representatives.
AB - Even with many changes in regulation in recent years, direct-to-consumer
advertising (DTCA) of pharmaceutical drugs remains a complicated and contentious
issue. Many in our society argue for increased legislation of DTCA while others
believe that DTCA serves a useful purpose and should not be overregulated. This
study was designed to compare attitudes and beliefs regarding DTCA held by two
key stakeholder groups, physicians and pharmaceutical sales representatives. A
questionnaire was created, pretested, and administered to 30 physicians and 30
pharmaceutical sales representatives to investigate these issues. Significant
differences between these two groups were found and implications for DTCA are
discussed.
PMID- 25120048
TI - Flow cytometric analysis of SOX11: a new diagnostic method for distinguishing B
cell chronic lymphocytic leukemia/small lymphocytic lymphoma from mantle cell
lymphoma.
AB - The differential diagnosis between mantle cell lymphoma (MCL) and B-cell chronic
lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL) is essential, since
MCL usually has a more aggressive clinical course. By flow cytometry both MCL and
B-CLL are CD19, CD20 and usually CD5 positive. However, ambiguities in other
immune phenotypic markers of these lymphoma entities sometimes complicate the
flow cytometric differential diagnosis. We here demonstrate that the
transcription factor SOX11, which is highly up-regulated in most MCL, can be
analyzed by flow cytometry. SOX11 protein could be consistently detected in ex
vivo isolated MCL but not in B-CLL/SLL. Flow cytometry also enabled protein
quantification, and SOX11 protein levels correlated with mRNA expression. We
suggest that implementing detection of SOX11 in diagnostic flow cytometry would
be beneficial for accurate and reliable diagnosis of MCL, especially for
distinguishing cases of MCL and B-CLL/SLL with aberrant immune phenotypes, and
for cases of rare cyclin D1 negative MCL.
PMID- 25120049
TI - Use of a claims database to characterize and estimate the incidence rate for
Castleman disease.
AB - Castleman disease (CD) is a rare lymphoproliferative disorder affecting single
(unicentric; UCD) or multiple (multicentric; MCD) lymph nodes. The incidence of
this difficult to diagnose disease is poorly understood, as no International
Classification of Diseases, Ninth Revision (ICD-9) code is available. This study
utilized a unique strategy to estimate its incidence using two commercial claims
databases, IMS LifeLinkTM and Truven Health Analytics MarketScan((r)). Patients
with an index diagnosis of lymphadenopathy (ICD-9 code 785.6) were followed
longitudinally for 1 year prior to and 2 years post-index diagnosis date. An
algorithm that identifies potential patients with CD was developed to determine
the incidence rate in person-years. The incidence rate for CD was calculated as
21 (IMS LifeLinkTM) and 25 (MarketScan((r))) per million person-years.
Additionally, 23% of patients with CD were identified as potentially suffering
from MCD. These results are consistent with the definition of an orphan disease,
and the low incidence of the disease estimated in the literature.
PMID- 25120050
TI - Incidence of secondary neoplasms in patients with acute promyelocytic leukemia
treated with all-trans retinoic acid plus chemotherapy or with all-trans retinoic
acid plus arsenic trioxide.
AB - The incidence and pattern of secondary neoplasms in patients with acute
promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA)
containing regimens is not well described. We compared 160 patients with APL
treated with ATRA plus idarubicin (n = 54) or ATRA plus arsenic trioxide (ATO) (n
= 106) for the incidence of secondary cancers per unit time of follow-up. Median
follow-up times for the two cohorts were 136 and 29 months, respectively. Nine
patients developed secondary cancers in the chemotherapy group. These included
two breast cancers, three myelodysplastic syndromes/acute myeloid leukemia, one
vulvar cancer, one prostate cancer, one colon cancer and one soft tissue sarcoma.
A melanoma and one pancreatic cancer developed in the ATO group. We conclude that
treatment of patients with APL using the non-chemotherapy regimen of ATRA plus
ATO is not associated with a higher incidence of secondary cancers (p = 0.29)
adjusted for unit time of exposure.
PMID- 25120053
TI - Erratum.
PMID- 25120051
TI - Transmission of angioimmunoblastic T-cell lymphoma by bone marrow transplant.
PMID- 25120052
TI - Underlying autoimmune diseases are not aggravated during treatment with
lenalidomide in patients with mucosa-associated lymphoid tissue lymphoma.
PMID- 25120055
TI - New limonoids from Hortia oreadica and unexpected coumarin from H. superba using
chromatography over cleaning Sephadex with sodium hypochlorite.
AB - Previous investigations of H. oreadica reported the presence of a wide spectrum
of complex limonoids and dihydrocinnamic acids. Our interest in the Rutaceae
motivated a reinvestigation of H. oreadica, H. brasiliana and H. superba
searching for other secondary metabolites present in substantial amounts for
taxonomic analysis. In a continuation of the investigation of the H. oreadica,
three new limonoids have now been isolated 9alpha-hydroxyhortiolide A, 11beta
hydroxyhortiolide C and 1(S*)-acetoxy-7(R*)-hydroxy-7-deoxoinchangin. All the
isolated compounds from the Hortia species reinforce its position in the
Rutaceae. With regard to limonoids the genus produces highly specialized
compounds, whose structural variations do not occur in any other member of the
Rutaceae, thus, it is evident from limonoid data that Hortia takes an isolated
position within the family. In addition, H. superba afforded the unexpected
coumarin 5-chloro-8-methoxy-psoralen, which may not be a genuine natural product.
Solid-state cross-polarisation/magic-angle-spinning 13C nuclear magnetic
resonance, X-Ray fluorescence and Field-emission gun scanning electron microscopy
experiments show that the Sephadex LH-20 was modified after treatment with NaOCl,
suggesting that when xanthotoxin (8-methoxy-psoralen) was extracted from cleaning
of the gel column, chlorination of the aromatic system occurred.
PMID- 25120054
TI - Bioevaluation of novel anti-biofilm coatings based on PVP/Fe3O4 nanostructures
and 2-((4-ethylphenoxy)methyl)-N- (arylcarbamothioyl)benzamides.
AB - Novel derivatives were prepared by reaction of aromatic amines with 2-(4
ethylphenoxymethyl)benzoyl isothiocyanate, affording the N-[2-(4
ethylphenoxymethyl) benzoyl]-N?-(substituted phenyl)thiourea. Structural
elucidation of these compounds was performed by IR, NMR spectroscopy and
elemental analysis. The new compounds were used in combination with Fe3O4 and
polyvinylpyrrolidone (PVP) for the coating of medical surfaces. In our
experiments, catheter pieces were coated by Matrix Assisted Pulsed Laser
Evaporation (MAPLE) technique. The microbial adherence ability was investigated
in 6 multi-well plates by using culture based methods. The obtained surfaces were
also assessed for their cytotoxicity with respect to osteoblast cells, by using
fluorescence microscopy and MTT assay. The prepared surfaces by advanced laser
processing inhibited the adherence and biofilm development ability of
Staphylococcus aureus and Pseudomonas aeruginosa tested strains while cytotoxic
effects on the 3T3-E1 preosteoblasts embedded in layer shaped alginate hydrogels
were not observed. These results suggest that the obtained medical surfaces,
based on the novel thiourea derivatives and magnetic nanoparticles with a
polymeric shell could represent a promising alternative for the development of
new and effective anti-infective strategies.
PMID- 25120056
TI - Synthesis and cytotoxic activity evaluation of novel arylpiperazine derivatives
on human prostate cancer cell lines.
AB - A series of novel arylpiperazine derivatives was synthesized. The in vitro
cytotoxic activities of all synthesized compounds against three human prostate
cancer cell lines (PC-3, LNCaP, and DU145) were evaluated by a CCK-8 assay.
Compounds 9 and 15 exhibited strong cytotoxic activities against LNCaP cells
(IC50<5 MUM), and compound 8 (IC50=8.25 MUM) possessed the most potent activity
against DU145 cells. However, these compounds also exhibited cytotoxicity towards
human epithelial prostate normal cells RWPE-1. The structure-activity
relationship (SAR) of these arylpiperazine derivatives was also discussed based
on the obtained experimental data.
PMID- 25120057
TI - Comparative pharmacokinetics study of sinomenine in rats after oral
administration of sinomenine monomer and Sinomenium acutum extract.
AB - Various products containing sinomenine monomer and extracts of Sinomenium acutum
have been widely applied in clinical treatments. The goal of the present study
was to compare the pharmacokinetics of sinomenine in rats after oral
administration of sinomenine monomer and Sinomenium acutum extract, and to
attempt to explore potential component-component interactions between the
constituents of this traditional Chinese herbal medicine. A reliable and specific
reversed phase high performance liquid chromatography method was developed to
analyze sinomenine in rat plasma. Pharmacokinetic parameters for sinomenine were
processed by non-compartmental analysis. The results showed that the maximum
concentration, the area under the concentration-time curve, clearance and the
apparent volume of distribution of sinomenine in the Sinomenium acutum extract
statistically differed from those of sinomenine monomer (p < 0.05); however, the
mean residence time, time of peak concentration, and half-life did not show
significant differences between the two groups. These findings suggested that
some additional components in the Sinomenium acutum extract may decrease the
absorption of sinomenine. The complex interactions between sinomenine and other
components of the herbal extract could result in the altered pharmacokinetic
behavior of sinomenine, which may subsequently cause different therapeutic and
detoxification effects.
PMID- 25120058
TI - Fused-ring derivatives of quinoxalines: spectroscopic characterization and
photoinduced processes investigated by EPR spin trapping technique.
AB - 10-Ethyl-7-oxo-7,10-dihydropyrido[2,3-f]quinoxaline derivatives, synthesized as
promising biologically/photobiologically active compounds were characterized by
UV/vis, FT-IR and fluorescent spectroscopy. Photoinduced processes of these
derivatives were studied by EPR spectroscopy, monitoring in situ the generation
of reactive intermediates upon UVA (lambdamax=365 nm) irradiation. The formation
of reactive oxygen species and further oxygen- and carbon-centered radical
intermediates was detected and possible reaction routes were suggested. To
quantify the investigated processes, the quantum yields of the superoxide radical
anion spin-adduct and 4-oxo-2,2,6,6-tetramethylpiperidine N-oxyl generation were
determined, reflecting the activation of molecular oxygen by the excited state of
the quinoxaline derivative.
PMID- 25120061
TI - Proposed International League Against Epilepsy Classification 2010: new insights.
AB - The International League Against Epilepsy (ILAE) Classification of Seizures in
1981 and the Classification of the Epilepsies, in 1989 have been widely accepted
the world over for the last 3 decades. Since then, there has been an explosive
growth in imaging, genetics and other fields in the epilepsies which have changed
many of our concepts. It was felt that a revision was in order and hence the ILAE
commissioned a group of experts who submitted the initial draft of this revised
classification in 2010. This review focuses on what are the strengths and
weaknesses of this new proposed classification, especially in the context of a
developing country.
PMID- 25120059
TI - Isocorydine derivatives and their anticancer activities.
AB - In order to improve the anticancer activity of isocorydine (ICD), ten isocorydine
derivatives were prepared through chemical structure modifications, and their in
vitro and in vivo activities were experimentally investigated. 8-Amino
isocorydine (8) and 6a,7-dihydrogen-isocorydione (10) could inhibit the growth of
human lung (A549), gastric (SGC7901) and liver (HepG2) cancer cell lines in
vitro. Isocorydione (2) could inhibit the tumor growth of murine sarcoma S180
bearing mice, and 8-acetamino-isocorydine (11), a pro-drug of 8-amino-isocorydine
(8), which is instable in water solution at room temperature, had a good
inhibitory effect on murine hepatoma H22-induced tumors. The results suggested
that the isocorydine structural modifications at C-8 could significantly improve
the biological activity of this alkaloid, indicating its suitability as a lead
compound in the development of an effective anticancer agent.
PMID- 25120060
TI - Expression of cytokeratin 8, vimentin, syndecan-1 and Ki-67 during human tooth
development.
AB - Spatio-temporal immunolocalizations of cytokeratin 8 (CK8), vimentin, syndecan-1
and Ki-67 were analyzed in ten human incisors and canine tooth germs between the
7th and 20th developmental weeks. CK8 expression was mild to moderate in the
epithelial tooth parts, while it shifted from absent or mild in its mesenchymal
parts, but few cells, sparsely distributed throughout the tooth germ, strongly
expressed CK8. As development progressed, CK8 expression increased to strong in
preameloblasts, while expression of vimentin increased to moderate in the
epithelial and mesenchymal tooth parts, particularly in the dental papilla and
sac. Co-expression of CK8 and vimentin was observed in some parts of the tooth
germ, and was increasing in the differentiating preameloblasts and
preodontoblasts. Syndecan-1 showed characteristic shift of expression from
epithelial to mesenchymal tooth parts, being particularly strong in dental
papilla, sac and cervical loops, while co-expression of Ki-67/syndecan-1 was
strong in the dental papilla. Our study demonstrated spatio-temporal expression
and restricted co-expression of the investigated markers, indicating
participation of CK8 and vimentin in cell proliferation and migration, and
differentiation of preodontoblasts and preameloblasts. Our data also suggest
involvement of syndecan-1 in morphogenesis of the developing tooth crown and
cervical loops, and together with CK8 and vimentin in differentiation of
preameloblasts and preodontoblasts.
PMID- 25120062
TI - Serum bisphenol A concentration and premature thelarche in female infants aged 4
month to 2-year.
AB - OBJECTIVES: To estimate the association between serum bisphenol A and premature
thelarche in female infants aged 4-mo to 2-y. METHODS: A total of 251 female
infants (aged 4 mo to 2 y) with premature thelarche and 33 healthy age-matched
control subjects were analyzed. All participants underwent physical examination
and serum bisphenol A was measured by ultra-performance liquid chromatography
tandem mass spectrometry. RESULTS: Serum bisphenol A concentration in the
premature thelarche group (3.48 ng/ml, 95%CI: 0.09-140.26) was significantly
higher than that in the control group (1.70 ng/ml, 95%CI: 0.06-51.78) (p =
0.039). There was no correlation between age and serum bisphenol A (BPA) level.
Univariate logistic regression analysis showed that serum BPA concentration
positively associated with premature thelarche, and the effect of BPA fell down
as the age grew. CONCLUSIONS: This hospital-based study implied that there is an
association between serum BPA concentrations and premature thelarche.
Additionally, serum BPA levels were markedly higher in infants aged 4-mo to 2-y
old, raising a concern for public health authorities.
PMID- 25120064
TI - Chikungunya virus transmission found in the United States: US health authorities
brace for wider spread.
PMID- 25120063
TI - ARID3B expression in primary breast cancers and breast cancer-derived cell lines.
AB - BACKGROUND: ARID3B (AT-rich interaction domain 3) is a member of the family of
ARID proteins, which constitutes evolutionarily conserved transcription factors
implicated in normal development, differentiation, cell cycle regulation and
chromatin remodeling. In addition, ARID3B has been linked to cellular
immortalization, epithelial-mesenchymal transition (EMT) and tumorigenesis. Given
the emerging role of ARID3B in tumor development, we examined its expression in
primary patient-derived breast cancer samples and breast cancer-derived cell
lines. METHODS: Immunohistochemistry (IHC) was used to detect ARID3B expression
in 63 formalin-fixed paraffin-embedded (FFPE) invasive breast cancer samples. In
addition, a panel of 6 (estrogen receptor-positive and -negative, ERBB2-positive
and -negative) breast cancer-derived cell lines and immortalized non-tumorigenic
epithelial breast cells were used for ARID3B expression analysis using RT-PCR.
Specific primers and Western blotting were used to detect ARID3B isoforms.
RESULTS: Using IHC, nuclear, cytoplasmic and low levels of membranous ARID3B
staining were detected in all 63 primary invasive breast tumors. Nuclear ARID3B
staining positively correlated with estrogen receptor (ER) status and negatively
correlated with tumor grade, mitotic index and ERBB2 status of the patients.
Increased nuclear expression of ARID3B was confirmed in breast cancer-derived
cell lines expressing ERalpha. In addition, two out of three ERBB2-positive
breast cancer cell lines were found to lack full length ARID3B. Three ARID3B
isoforms were found to be present in normal breast epithelial cells as well as in
breast cancer cells. CONCLUSION: We report a positive correlation between ER
positivity and nuclear ARID3B expression in primary breast cancers, along with a
negative correlation with the ERBB2 status. Very similar correlations were noted
in breast cancer-derived cell lines. Since in the recent past ARID3B expression
has increasingly been related to cancer-associated proteins and microRNAs,
knowledge on ARID3B expression and function may be instrumental for gaining
further insight into potentially important cancer-related networks.
PMID- 25120068
TI - A symposium in honor of Peter B. Dervan, the 2014 ACS Chemical Biology
Lectureship Award Winner.
PMID- 25120070
TI - Lack of evidence that Tonkean macaques understand what others can hear.
AB - By distinguishing the attentional cues of their mates, animals can learn what
part of their environment is of potential interest. However, recognizing the
attentional states of others through auditory perception appears to be difficult,
since these states are generally not accompanied by ostensive signals liable to
reveal them. In this context, one study found that rhesus macaques withhold their
action when unobserved, then concluding that they know what others can hear. We
replicated this study by testing 18 Tonkean macaques in an experimental setting
where subjects had to choose between two boxes containing a food reward. One box
made a noise when opened, and the other opened silently. An experimenter was
present and could either have her back to subjects or be facing them. If subjects
aimed to avoid attracting the experimenter's attention, they were expected to
select the silent box while the experimenter's back was turned. Results showed
that subjects did not discriminate between boxes, whatever the experimenter's
position. We thus found no evidence that Tonkean macaques are able to take the
auditory attentional states of a human into account. It is therefore premature to
conclude that monkeys can establish a link between hearing and knowing.
PMID- 25120072
TI - Lives of a journal.
PMID- 25120073
TI - Effect of the cation on the interactions between alkyl methyl imidazolium
chloride ionic liquids and water.
AB - A systematic study of the interactions between water and alkyl methyl imidazolium
chloride ionic liquids at 298.2 K, based on activity coefficients estimated from
water activity measurements in the entire solubility range, is presented. The
results show that the activity coefficients of water in the studied ILs are
controlled by the hydrophilicity of the cation and the cation-anion interaction.
To achieve a deeper understanding on the interactions between water and the ILs,
COSMO-RS and FTIR spectroscopy were also applied. COSMO-RS was used to predict
the activity coefficient of water in the studied ionic liquids along with the
excess enthalpies, suggesting the formation of complexes between three molecules
of water and one IL molecule. On the basis of quantum-chemical calculations, it
is found that cation-anion interaction plays an important role upon the ability
of the IL anion to interact with water. The changes in the peak positions/band
areas of OH vibrational modes of water as a function of IL concentration were
investigated, and the impact of the cation on the hydrogen-bonding network of
water is identified and discussed.
PMID- 25120071
TI - Development and performance of a 129-GHz dynamic nuclear polarizer in an ultra
wide bore superconducting magnet.
AB - OBJECTIVE: We sought to build a dynamic nuclear polarization system for operation
at 4.6 T (129 GHz) and evaluate its efficiency in terms of (13)C polarization
levels using free radicals that span a range of ESR linewidths. MATERIALS AND
METHODS: A liquid helium cryostat was placed in a 4.6 T superconducting magnet
with a 150-mm warm bore diameter. A 129-GHz microwave source was used to
irradiate (13)C enriched samples. Temperatures close to 1 K were achieved using a
vacuum pump with a 453-m(3)/h roots blower. A hyperpolarized (13)C nuclear
magnetic resonance (NMR) signal was detected using a saddle coil and a Varian
VNMRS console operating at 49.208 MHz. Samples doped with free radicals BDPA (1,3
bisdiphenylene-2-phenylallyl), trityl OX063 (tris{8-carboxyl-2,2,6,6-benzo(1,2
d:4,5-d)-bis(1,3)dithiole-4-yl}methyl sodium salt), galvinoxyl ((2,6-di-tert
butyl-alpha-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien-1-ylidene)-p-tolyloxy),
2,2-diphenylpicrylhydrazyl (DPPH) and 4-oxo-TEMPO (4-Oxo-2,2,6,6-tetramethyl-1
piperidinyloxy) were assayed. Microwave dynamic nuclear polarization (DNP)
spectra and solid-state (13)C polarization levels for these samples were
determined. RESULTS: (13)C polarization levels close to 50 % were achieved for [1
(13)C]pyruvic acid at 1.15 K using the narrow electron spin resonance (ESR)
linewidth free radicals trityl OX063 and BDPA, while 10-20 % (13)C polarizations
were achieved using galvinoxyl, DPPH and 4-oxo-TEMPO. CONCLUSION: At this field
strength free radicals with smaller ESR linewidths are still superior for DNP of
(13)C as opposed to those with linewidths that exceed that of the (1)H Larmor
frequency.
PMID- 25120074
TI - Synthesis of NaLuF4-based nanocrystals and large enhancement of upconversion
luminescence of NaLuF4:Gd, Yb, Er by coating an active shell for bioimaging.
AB - A series of NaLuF4-based hexagonal phase upconversion nanocrystals (UCNs) were
synthesized by a facile solvothermal method and the properties of the UCNs were
investigated. The results show that the as-prepared nanocrystals exhibit pure
hexagonal lattice structures, uniform morphologies, high monodispersities and
excellent upconversion luminescence. The upconversion luminescence (UCL)
intensities of the UCNs can be enhanced by coating with a shell of NaLuF4. More
interestingly, the UCL intensities of active-shell coated nanocrystals
(NaLuF4:Gd, Yb, Er@NaLuF4:Yb, Ho and NaLuF4:Gd, Yb, Er@NaLuF4:Yb) are remarkably
higher than that of inert-shell coated nanocrystals (NaLuF4:Gd, Yb, Er@NaLuF4),
and NaLuF4:Gd, Yb, Er@NaLuF4:Yb, Ho is higher than NaLuF4:Gd, Yb, Er@NaLuF4:Yb.
The mechanisms of upconversion luminescence enhancement are discussed in detail.
The bioimaging application of the nanocrystals showed that bright upconversion
luminescence was observed when UCNs-labeled HeLa cells were excited with 980 nm
light. This study presents a facile method for the synthesis of NaLuF4-based
upconversion nanocrystals with intense luminescence that can be used as potential
fluorescent probes for sensitive bioimaging, and the suggested mechanism could
provide new insights into fabrication of upconversion materials with high
upconversion fluorescence.
PMID- 25120075
TI - Functional alterations in the dorsal raphe nucleus following acute and chronic
ethanol exposure.
AB - Alcoholism is a pervasive disorder perpetuated in part to relieve negative mood
states like anxiety experienced during alcohol withdrawal. Emerging evidence
demonstrates a role for the serotonin-rich dorsal raphe (DR) in anxiety following
ethanol withdrawal. The current study examined the effects of chronic ethanol
vapor exposure on the DR using slice electrophysiology in male DBA2/J mice. We
found that chronic ethanol exposure resulted in deficits in social approach
indicative of increased anxiety-like behavior at both 24 h and 7 days post
ethanol exposure. At 24 h post-ethanol exposure, we observed increased
excitability and decreased spontaneous inhibitory transmission (inhibitory
postsynaptic currents, IPSCs) in the DR. At 7 days post-ethanol exposure, we
observed increased spontaneous and miniature excitatory transmission (excitatory
postsynaptic currents, EPSCs). Because acute ethanol alters GABA transmission in
other brain regions, we assessed the effects of ex vivo ethanol (50 mM) on
miniature IPSCs (mIPSCs) in the DR 24-h post-ethanol exposure. Bath application
of ethanol enhanced the amplitude of mIPSCs in cells from ethanol-naive and
chronic intermittent ethanol-exposed (CIE) mice, but significantly enhanced the
frequency of mIPSCs only in cells from CIE mice, suggesting that DR neurons are
more sensitive to the inhibitory effects of acute ethanol following CIE. On the
basis of these findings, we hypothesize that net excitation of DR neurons
following chronic ethanol exposure contributes to enhanced anxiety during ethanol
withdrawal, and that increased sensitivity of DR neurons to subsequent ethanol
exposure may mediate acute ethanol's ability to relieve anxiety during ethanol
withdrawal.
PMID- 25120076
TI - High locomotor reactivity to novelty is associated with an increased propensity
to choose saccharin over cocaine: new insights into the vulnerability to
addiction.
AB - Drug addiction is associated with a relative devaluation of natural or socially
valued reinforcers that are unable to divert addicts from seeking and consuming
the drug. Before protracted drug exposure, most rats prefer natural rewards, such
as saccharin, over cocaine. However, a subpopulation of animals prefer cocaine
over natural rewards and are thought to be vulnerable to addiction. Specific
behavioral traits have been associated with different dimensions of drug
addiction. For example, anxiety predicts loss of control over drug intake whereas
sensation seeking and sign-tracking are markers of a greater sensitivity to the
rewarding properties of the drug. However, how these behavioral traits predict
the disinterest for natural reinforcers remains unknown. In a population of rats,
we identified sensation seekers (HR) on the basis of elevated novelty-induced
locomotor reactivity, high anxious rats (HA) based on the propensity to avoid
open arms in an elevated-plus maze and sign-trackers (ST) that are prone to
approach, and interaction with, reward-associated stimuli. Rats were then tested
on their preference for saccharin over cocaine in a discrete-trial choice
procedure. We show that HR rats display a greater preference for saccharin over
cocaine compared with ST and HA whereas the motivation for the drug was
comparable between the three groups. The present data suggest that high locomotor
reactivity to novelty, or sensation seeking, by predisposing to an increased
choice toward non-drug rewards at early stages of drug use history, may prevent
the establishment of chronic cocaine use.
PMID- 25120078
TI - Use of ultrasound in the insertion of a vascular closure device: a comparative
retrospective study with the standard blind technique.
AB - PURPOSE: To evaluate whether ultrasound (US) assistance can decrease the rate of
complications related to the use of vascular closure devices (VCDs). MATERIALS
AND METHODS: A retrospective comparative study was done on 150 consecutive
patients who had a VCD inserted under US guidance after retrograde common-femoral
artery (CFA) puncture. This group was compared to a historical control group of
150 consecutive patients who had the same VCDs inserted with the standard blind
technique. After the procedures, patients were placed at bedrest for at least 6
h. Technical success, defined as correct deployment without adjunctive manual
compression, blood count and US evaluation of the arterial puncture site was done
at 24 h and at 3 months. Differences in terms of efficacy and safety were
statistically evaluated using US guidance as a predictor for a lower complication
rate. RESULTS: Technical success was achieved in 147/150 patients (98 %) in the
study group vs. 141/150 cases (94 %) of the control group (p = 0.038). In three
cases (2 %) adjunctive manual compression (<=5 min) was required. One
pseudoaneurysm (0.65 %) occurred after 24 h, solved with manual compression. Six
minor complications (4 %)--haematoma (n = 5; 3.35 %), recurrent wound bleeding (n
= 1; 0.65 %)--were reported. In the control group four (2.65 %) major
complications occurred: CFA occlusion managed with surgical bypass, CFA
dissection solved by surgical bypass, two pseudoaneurysms solved with manual
compression. Thirteen (8.65 %) minor complications were observed with haematoma
(n = 10; 6.65 %), and recurrent wound bleeding (n = 3; 2.0 %). The comparative
analysis of the total complication rate and major complication rate between the
study group and the control group was statistically significant (p = 0.016 and p
= 0.049, respectively). A 24-h evaluation showed a triphasic flow within the CFA
in 150/150 patients (100 %) of the study group and in 146/150 cases (97.35 %) of
the control group. CONCLUSION: VCD inserted under US guidance increases the
success rate reducing the number of complications.
PMID- 25120079
TI - Mammotome((r)) and EnCor ((r)): comparison of two systems for stereotactic vacuum
assisted core biopsy in the characterisation of suspicious mammographic
microcalcifications alone.
AB - PURPOSE: The authors sought to compare the diagnostic performance of the
Mammotome((r)) and EnCor((r)) vacuum-assisted breast biopsy (VABB) systems in the
assessment of suspicious mammographic microcalcifications. MATERIALS AND METHODS:
Between January 2011 and July 2012, a total of 169 VABB were performed by
stereotactic guidance on a prone table. The Mammotome((r)) 11G (S1) or EnCor((r))
10G (S2) probes were used randomly. Sampling time and the number of frustules
collected were considered; sensitivity, specificity, diagnostic accuracy,
positive and negative predictive value (PPV, NPV) of both procedures were
evaluated, considering the final histological examination as reference (B1, B3,
B5 lesions underwent surgical excision; B2 lesion were considered confirmed after
a negative follow-up of at least 1 year). RESULTS: There were no statistically
significant differences between the two groups of patients according to the
number of procedures (S1 82/169; S2 87/169), average age, BIRADS category (4a,
b), and average size of the lesions. The two systems did not differ statistically
for correlation with the final histology (S1 k = 0.94 +/- 0.06; S2 k = 0.92 +/-
0.08) and underestimation of B3 lesions or in situ (S1 4.5%; S2 4.3%).
Sensitivity, specificity, PPV, NPV, diagnostic accuracy of S1 and S2 were also
not statistically different. The systems differed only in sampling time (S1 80;
S2 63 s), but not in total procedure time. CONCLUSIONS: Our study confirms the
effectiveness of VABB in the assessment of microcalcifications and highlights the
lack of significant differences between the two systems in terms of diagnostic
performance.
PMID- 25120080
TI - Regarding hypertension treatment are we following worldwide tendencies?
PMID- 25120077
TI - Blonanserin ameliorates phencyclidine-induced visual-recognition memory deficits:
the complex mechanism of blonanserin action involving D3-5-HT2A and D1-NMDA
receptors in the mPFC.
AB - Blonanserin differs from currently used serotonin 5-HT2A/dopamine-D2 receptor
antagonists in that it exhibits higher affinity for dopamine-D2/3 receptors than
for serotonin 5-HT2A receptors. We investigated the involvement of dopamine-D3
receptors in the effects of blonanserin on cognitive impairment in an animal
model of schizophrenia. We also sought to elucidate the molecular mechanism
underlying this involvement. Blonanserin, as well as olanzapine, significantly
ameliorated phencyclidine (PCP)-induced impairment of visual-recognition memory,
as demonstrated by the novel-object recognition test (NORT) and increased
extracellular dopamine levels in the medial prefrontal cortex (mPFC). With
blonanserin, both of these effects were antagonized by DOI (a serotonin 5-HT2A
receptor agonist) and 7-OH-DPAT (a dopamine-D3 receptor agonist), whereas the
effects of olanzapine were antagonized by DOI but not by 7-OH-DPAT. The
ameliorating effect was also antagonized by SCH23390 (a dopamine-D1 receptor
antagonist) and H-89 (a protein kinase A (PKA) inhibitor). Blonanserin
significantly remediated the decrease in phosphorylation levels of PKA at
Thr(197) and of NR1 (an essential subunit of N-methyl-D-aspartate (NMDA)
receptors) at Ser(897) by PKA in the mPFC after a NORT training session in the
PCP-administered mice. There were no differences in the levels of NR1
phosphorylated at Ser(896) by PKC in any group. These results suggest that the
ameliorating effect of blonanserin on PCP-induced cognitive impairment is
associated with indirect functional stimulation of the dopamine-D1-PKA-NMDA
receptor pathway following augmentation of dopaminergic neurotransmission due to
inhibition of both dopamine-D3 and serotonin 5-HT2A receptors in the mPFC.
PMID- 25120081
TI - Impact of different obesity assessment methods after acute coronary syndromes.
AB - BACKGROUND: Abdominal obesity is an important cardiovascular risk factor.
Therefore, identifying the best method for measuring waist circumference (WC) is
a priority. OBJECTIVE: To evaluate the eight methods of measuring WC in patients
with acute coronary syndrome (ACS) as a predictor of cardiovascular complications
during hospitalization. METHODS: Prospective study of patients with ACS. The
measurement of WC was performed by eight known methods: midpoint between the last
rib and the iliac crest (1), point of minimum circumference (2); immediately
above the iliac crest (3), umbilicus (4), one inch above the umbilicus (5), one
centimeter above the umbilicus (6), smallest rib and (7) the point of greatest
circumference around the waist (8). Complications included: angina, arrhythmia,
heart failure, cardiogenic shock, hypotension, pericarditis and death. Logistic
regression tests were used for predictive factors. RESULTS: A total of 55
patients were evaluated. During the hospitalization period, which corresponded on
average to seven days, 37 (67%) patients had complications, with the exception of
death, which was not observed in any of the cases. Of these complications, the
only one that was associated with WC was angina, and with every cm of WC
increase, the risk for angina increased from 7.5 to 9.9%, depending on the
measurement site. It is noteworthy the fact that there was no difference between
the different methods of measuring WC as a predictor of angina. CONCLUSION: The
eight methods of measuring WC are also predictors of recurrent angina after acute
coronary syndromes.
PMID- 25120082
TI - Resistance exercise restores endothelial function and reduces blood pressure in
type 1 diabetic rats.
AB - BACKGROUND: Resistance exercise effects on cardiovascular parameters are not
consistent. OBJECTIVES: The effects of resistance exercise on changes in blood
glucose, blood pressure and vascular reactivity were evaluated in diabetic rats.
METHODS: Wistar rats were divided into three groups: control group (n = 8);
sedentary diabetic (n = 8); and trained diabetic (n = 8). Resistance exercise was
carried out in a squat device for rats and consisted of three sets of ten
repetitions with an intensity of 50%, three times per week, for eight weeks.
Changes in vascular reactivity were evaluated in superior mesenteric artery
rings. RESULTS: A significant reduction in the maximum response of acetylcholine
induced relaxation was observed in the sedentary diabetic group (78.1 +/- 2%) and
an increase in the trained diabetic group (95 +/- 3%) without changing potency.
In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced
relaxation was significantly reduced in the control and trained diabetic groups,
but not in the sedentary diabetic group. Furthermore, a significant increase (p <
0.05) in mean arterial blood pressure was observed in the sedentary diabetic
group (104.9 +/- 5 to 126.7 +/- 5 mmHg) as compared to that in the control group.
However, the trained diabetic group showed a significant decrease (p < 0.05) in
the mean arterial blood pressure levels (126.7 +/- 5 to 105.1 +/- 4 mmHg) as
compared to the sedentary diabetic group. CONCLUSIONS: Resistance exercise could
restore endothelial function and prevent an increase in arterial blood pressure
in type 1 diabetic rats.
PMID- 25120083
TI - Evaluation of sexual dimorphism in the efficacy and safety of
simvastatin/atorvastatin therapy in a southern Brazilian cohort.
AB - BACKGROUND: Dyslipidemia is the primary risk factor for cardiovascular disease,
and statins have been effective in controlling lipid levels. Sex differences in
the pharmacokinetics and pharmacodynamics of statins contribute to
interindividual variations in drug efficacy and toxicity. OBJECTIVE: To evaluate
the presence of sexual dimorphism in the efficacy and safety of
simvastatin/atorvastatin treatment. METHODS: Lipid levels of 495 patients (331
women and 164 men) were measured at baseline and after 6 +/- 3 months of
simvastatin/atorvastatin treatment to assess the efficacy and safety profiles of
both drugs. RESULTS: Women had higher baseline levels of total cholesterol (TC),
low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein
cholesterol (HDL-C) compared with men (p < 0.0001). After treatment, women
exhibited a greater decrease in plasma TC and LDL-C levels compared with men.
After adjustment for covariates, baseline levels of TC and LDL-C influenced more
than 30% of the efficacy of lipid-lowering therapy (p < 0.001), regardless of
sex. Myalgia [with or without changes in creatine phosphokinase (CPK) levels]
occurred more frequently in women (25.9%; p = 0.002), whereas an increase in CPK
and/or abnormal liver function was more frequent in in men (17.9%; p = 0.017).
CONCLUSIONS: Our results show that baseline TC and LDL-C levels are the main
predictors of simvastatin/atorvastatin therapy efficacy, regardless of sex. In
addition, they suggest the presence of sexual dimorphism in the safety of
simvastatin/atorvastatin. The effect of sex differences on receptors, transporter
proteins, and gene expression pathways needs to be better evaluated and
characterized to confirm these observations.
PMID- 25120084
TI - Obesity does not lead to imbalance between myocardial phospholamban
phosphorylation and dephosphorylation.
AB - BACKGROUND: The activation of the beta-adrenergic system promotes G protein
stimulation that, via cyclic adenosine monophosphate (cAMP), alters the structure
of protein kinase A (PKA) and leads to phospholamban (PLB) phosphorylation. This
protein participates in the system that controls intracellular calcium in muscle
cells, and it is the primary regulator of sarcoplasmic reticulum calcium pump
activity. In obesity, the beta-adrenergic system is activated by the influence of
increased leptin, therefore, resulting in higher myocardial phospholamban
phosphorylation via cAMP-PKA. OBJECTIVE: To investigate the involvement of
proteins which regulate the degree of PLB phosphorylation due to beta-adrenergic
activation in obesity. In the present study, we hypothesized that there is an
imbalance between phospholamban phosphorylation and dephosphorylation, with
prevalence of protein phosphorylation. METHODS: Male Wistar rats were randomly
distributed into two groups: control (n = 14), fed with normocaloric diet; and
obese (n = 13), fed with a cycle of four unsaturated high-fat diets. Obesity was
determined by the adiposity index, and protein expressions of phosphatase 1 (PP
1), PKA, PLB, phosphorylated phospholamban at serine16 (PPLB-Ser16) were assessed
by Western blot. RESULTS: Obesity caused glucose intolerance, hyperinsulinemia,
hypertriglyceridemia, hyperleptinemia and did not alter the protein expression of
PKA, PP-1, PLB, PPLB-Ser16. CONCLUSION: Obesity does not promote an imbalance
between myocardial PLB phosphorylation and dephosphorylation via beta-adrenergic
system.
PMID- 25120085
TI - High-sensitivity C-reactive protein as a predictor of cardiovascular events after
ST-elevation myocardial infarction.
AB - BACKGROUND: The association between high-sensitivity C-reactive protein and
recurrent major adverse cardiovascular events (MACE) in patients with ST
elevation myocardial infarction who undergo primary percutaneous coronary
intervention remains controversial. OBJECTIVE: To investigate the potential
association between high-sensitivity C-reactive protein and an increased risk of
MACE such as death, heart failure, reinfarction, and new revascularization in
patients with ST-elevation myocardial infarction treated with primary
percutaneous coronary intervention. METHODS: This prospective cohort study
included 300 individuals aged >18 years who were diagnosed with ST-elevation
myocardial infarction and underwent primary percutaneous coronary intervention at
a tertiary health center. An instrument evaluating clinical variables and the
Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute
Coronary Events (GRACE) risk scores was used. High-sensitivity C-reactive protein
was determined by nephelometry. The patients were followed-up during
hospitalization and up to 30 days after infarction for the occurrence of MACE.
Student's t, Mann-Whitney, chi-square, and logistic regression tests were used
for statistical analyses. P values of <=0.05 were considered statistically
significant. RESULTS: The mean age was 59.76 years, and 69.3% of patients were
male. No statistically significant association was observed between high
sensitivity C-reactive protein and recurrent MACE (p = 0.11). However, high
sensitivity C-reactive protein was independently associated with 30-day mortality
when adjusted for TIMI [odds ratio (OR), 1.27; 95% confidence interval (CI), 1.07
1.51; p = 0.005] and GRACE (OR, 1.26; 95% CI, 1.06-1.49; p = 0.007) risk scores.
CONCLUSION: Although high-sensitivity C-reactive protein was not predictive of
combined major cardiovascular events within 30 days after ST-elevation myocardial
infarction in patients who underwent primary angioplasty and stent implantation,
it was an independent predictor of 30-day mortality.
PMID- 25120087
TI - Case 3/2014--81-year-old patient hospitalized for decompensated heart failure.
PMID- 25120089
TI - Valvular heart team.
PMID- 25120086
TI - Lipoprotein (a): structure, pathophysiology and clinical implications.
AB - The chemical structure of lipoprotein (a) is similar to that of LDL, from which
it differs due to the presence of apolipoprotein (a) bound to apo B100 via one
disulfide bridge. Lipoprotein (a) is synthesized in the liver and its plasma
concentration, which can be determined by use of monoclonal antibody-based
methods, ranges from < 1 mg to > 1,000 mg/dL. Lipoprotein (a) levels over 20-30
mg/dL are associated with a two-fold risk of developing coronary artery disease.
Usually, black subjects have higher lipoprotein (a) levels that, differently from
Caucasians and Orientals, are not related to coronary artery disease. However,
the risk of black subjects must be considered. Sex and age have little influence
on lipoprotein (a) levels. Lipoprotein (a) homology with plasminogen might lead
to interference with the fibrinolytic cascade, accounting for an atherogenic
mechanism of that lipoprotein. Nevertheless, direct deposition of lipoprotein (a)
on arterial wall is also a possible mechanism, lipoprotein (a) being more prone
to oxidation than LDL. Most prospective studies have confirmed lipoprotein (a) as
a predisposing factor to atherosclerosis. Statin treatment does not lower
lipoprotein (a) levels, differently from niacin and ezetimibe, which tend to
reduce lipoprotein (a), although confirmation of ezetimibe effects is pending.
The reduction in lipoprotein (a) concentrations has not been demonstrated to
reduce the risk for coronary artery disease. Whenever higher lipoprotein (a)
concentrations are found, and in the absence of more effective and well-tolerated
drugs, a more strict and vigorous control of the other coronary artery disease
risk factors should be sought.
PMID- 25120088
TI - Bioresorbable vascular scaffold use in a case of in-stent restenosis.
PMID- 25120090
TI - Insights of optical coherence tomography in renal artery fibromuscular dysplasia
in a patient with spontaneous coronary artery dissection.
PMID- 25120093
TI - Development of CMX001 (Brincidofovir) for the treatment of serious diseases or
conditions caused by dsDNA viruses.
AB - CMX001 (hexadecyloxypropyl-cidofovir, Brincidofovir) is a broad spectrum, lipid
conjugate of cidofovir that is converted intracellularly into the active
antiviral, cidofovir diphosphate. The lipid conjugation results in oral
bioavailability, higher intracellular concentrations of active drug, lower plasma
concentrations of cidofovir and increased antiviral potency against dsDNA
viruses.
PMID- 25120091
TI - Multivalent polymers for drug delivery and imaging: the challenges of
conjugation.
AB - Multivalent polymers offer a powerful opportunity to develop theranostic
materials on the size scale of proteins that can provide targeting, imaging, and
therapeutic functionality. Achieving this goal requires the presence of multiple
targeting molecules, dyes, and/or drugs on the polymer scaffold. This critical
review examines the synthetic, analytical, and functional challenges associated
with the heterogeneity introduced by conjugation reactions as well as polymer
scaffold design. First, approaches to making multivalent polymer conjugations are
discussed followed by an analysis of materials that have shown particular promise
biologically. Challenges in characterizing the mixed ligand distributions and the
impact of these distributions on biological applications are then discussed.
Where possible, molecular-level interpretations are provided for the structures
that give rise to the functional ligand and molecular weight distributions
present in the polymer scaffolds. Lastly, recent strategies employed for
overcoming or minimizing the presence of ligand distributions are discussed. This
review focuses on multivalent polymer scaffolds where average stoichiometry
and/or the distribution of products have been characterized by at least one
experimental technique. Key illustrative examples are provided for scaffolds that
have been carried forward to in vitro and in vivo testing with significant
biological results.
PMID- 25120092
TI - Identification of a human neonatal immune-metabolic network associated with
bacterial infection.
AB - Understanding how human neonates respond to infection remains incomplete. Here, a
system-level investigation of neonatal systemic responses to infection shows a
surprisingly strong but unbalanced homeostatic immune response; developing an
elevated set-point of myeloid regulatory signalling and sugar-lipid metabolism
with concomitant inhibition of lymphoid responses. Innate immune-negative
feedback opposes innate immune activation while suppression of T-cell co
stimulation is coincident with selective upregulation of CD85 co-inhibitory
pathways. By deriving modules of co-expressed RNAs, we identify a limited set of
networks associated with bacterial infection that exhibit high levels of inter
patient variability. Whereas, by integrating immune and metabolic pathways, we
infer a patient-invariant 52-gene-classifier that predicts bacterial infection
with high accuracy using a new independent patient population. This is further
shown to have predictive value in identifying infection in suspected cases with
blood culture-negative tests. Our results lay the foundation for future
translation of host pathways in advancing diagnostic, prognostic and therapeutic
strategies for neonatal sepsis.
PMID- 25120094
TI - Neurogenin 3 is important but not essential for pancreatic islet development in
humans.
PMID- 25120096
TI - Orbital Lipomatosis: A Complication of Steroid Therapy in the Sweet Syndrome.
AB - The description of a Sweet syndrome steroid dependant-induced orbital lipomatosis
is reported. A 76-year-old-man with history of Sweet syndrome presented with
severe bilateral proptosis (Hertel value, 25 mm) with decreased visual acuity and
evoked potentials lengthened. A bilateral transpalpebral orbital decompression
was performed by resection of intraorbital fat without bone removal. The surgery
was uneventful. The volume of resected orbital fat was 15 ml for both sides.
Proptosis reduction was 6 mm. Postoperative Hertel values were 19 mm, and evoked
potentials were improved. The proptosis was managed successfully. Orbital
lipectomy led to minimal sequelae and may be repeated if necessary in this case.
PMID- 25120095
TI - Macrophage mTORC1 disruption reduces inflammation and insulin resistance in obese
mice.
AB - AIMS/HYPOTHESIS: Inflammatory factors secreted by macrophages play an important
role in obesity-related insulin resistance. Being at the crossroads of a nutrient
hormonal signalling network, the mammalian target of rapamycin complex 1 (mTORC1)
controls important functions in the regulation of energy balance and peripheral
metabolism. However, the role of macrophage mTORC1 in insulin resistance is still
unclear. In the current study, we investigated the physiological role of
macrophage mTORC1 in regulating inflammation and insulin sensitivity. METHODS: We
generated mice deficient in the regulatory associated protein of mTOR (Raptor) in
macrophages, by crossing Raptor (also known as Rptor) floxed mice (Raptor
(flox/flox)) with mice expressing Cre recombinase under the control of the Lysm
Cre promoter (Mac-Raptor (KO)). We fed mice chow or high-fat diet (HFD) and
assessed insulin sensitivity in liver, muscle and adipose tissue. Subsequently,
we measured inflammatory gene expression in liver and adipose tissue and
investigated the role of Raptor deficiency in the regulation of inflammatory
responses in peritoneal macrophages from HFD-fed mice or in palmitic acid
stimulated bone marrow-derived macrophages (BMDMs). RESULTS: Mac-Raptor (KO) mice
fed HFD had improved systemic insulin sensitivity compared with Raptor
(flox/flox) mice. Macrophage Raptor deficiency reduced inflammatory gene
expression in liver and adipose tissue, fatty liver and adipose tissue macrophage
content in response to HFD. In peritoneal macrophages from mice fed with an HFD
for 12 weeks, macrophage Raptor deficiency decreased inflammatory gene
expression, through attenuation of the inactivation of Akt and subsequent
inhibition of the inositol-requiring element 1alpha/clun NH2-terminal kinase
nuclear factor kappa-light-chain-enhancer of activated B cells
(IRE1alpha/JNK/NFkappaB) pathways. Similarly, mTOR inhibition as a result of
Raptor deficiency or rapamycin treatment decreased palmitic acid-induced
inflammatory gene expression in BMDMs in vitro. CONCLUSIONS/INTERPRETATION: The
disruption of mTORC1 signalling in macrophages protects mice against inflammation
and insulin resistance potentially by inhibiting HFD- and palmitic acid-induced
IRE1alpha/JNK/NFkappaB pathway activation.
PMID- 25120097
TI - Exercise for people with high cardiovascular risk.
AB - BACKGROUND: When two or more cardiovascular risk factors occur in one individual,
they may interact in a multiplicative way promoting cardiovascular disease.
Exercise has proven to be effective in controlling individual risk factors but
its effect on overall cardiovascular risk remains uncertain. OBJECTIVES: To
assess the effects of exercise training in people with increased cardiovascular
risk but without a concurrent cardiovascular disease on general cardiovascular
mortality, incidence of cardiovascular events, and total cardiovascular risk.
SEARCH METHODS: A search was conducted in CENTRAL (The Cochrane Library 2013,
Issue 10 of 12), Ovid MEDLINE (1946 to week 2 November 2013), EMBASE Classic +
EMBASE via Ovid (1947 to Week 47 2013), CINAHL Plus with Full Text via EBSCO (to
November 2013), Science Citation Index Expanded (SCI-EXPANDED) (1970 to 22
November 2013), and Conference Proceedings Citation Index - Science (CPCI-S)
(1990 to 22 November 2013) on Web of Science (Thomson Reuters). We did not apply
any date or language restrictions. SELECTION CRITERIA: Randomized clinical trials
comparing aerobic or resistance exercise training versus no exercise or any
standard approach that does not include exercise. Participants had to be 18 years
of age or older with an average 10-year Framingham risk score of 10% for
cardiovascular disease over 10 years, or with two or more cardiovascular risk
factors, and no history of cardiovascular disease. DATA COLLECTION AND ANALYSIS:
The selection of studies and subsequent data collection process were conducted by
two independent authors. Disagreements were solved by consensus. The results were
reported descriptively. It was not possible to conduct a meta-analysis because of
the high heterogeneity and high risk of bias in the included studies. MAIN
RESULTS: A total of four studies were included that involved 823 participants,
412 in the exercise group and 411 in the control group. Follow-up of participants
ranged from 16 weeks to 6 months. Overall, the included studies had a high risk
of selection, detection, and attrition bias. Meta-analysis was not possible
because the interventions (setting, type and intensity of exercise) and outcome
measurements were not comparable, and the risk of bias in the identified studies
was high. No study assessed cardiovascular or all-cause mortality or
cardiovascular events as individual outcomes. One or more of the studies reported
on total cardiovascular risk, low-density lipoprotein (LDL) and high-density
lipoprotein (HDL) cholesterol, blood pressure, body mass index, exercise
capacity, and health-related quality of life but the available evidence was not
sufficient to determine the effectiveness of exercise. Adverse events and smoking
cessation were not assessed in the included studies. AUTHORS' CONCLUSIONS:
Evidence to date is entirely limited to small studies with regard to sample size,
short-term follow-up, and high risk of methodological bias, which makes it
difficult to derive any conclusions on the efficacy or safety of aerobic or
resistance exercise on groups with increased cardiovascular risk or in
individuals with two or more coexisting risk factors. Further randomized clinical
trials assessing controlled exercise programmes on total cardiovascular risk in
individuals are warranted.
PMID- 25120098
TI - Aberrant expression of B7-H3 in gastric adenocarcinoma promotes cancer cell
metastasis.
AB - B7-H3 belongs to the B7 superfamily, a group of molecules that costimulate or
downmodulate T cell responses. Although it has been shown that B7-H3 can inhibit
T cell responses, several studies, most of them performed in murine systems,
found B7-H3 to act in a co-stimulatory manner. In addition, B7-H3 is also
expressed in various human cancers and is correlated with the poor outcome of
cancer patients. The functional role of B7-H3 in cancer is still controversially
discussed. In the present study, we compared B7-H3 expression in normal gastric
tissues and gastric cancer tissue specimens and determined the effects of low B7
H3 expression on the human gastric cancer cell line SGC-7901 by using RNAi. B7-H3
expression in gastric specimens was determined by tissue qPCR and
immunohistochemisty. A SGC-7901 cell line with low B7-H3 expression was
established by lentiviral-mediated RNA interference to investigate the effect of
B7-H3 on cancer cell migration and invasion in vitro. By establishing an
orthotopic transplantation gastric cancer mouse model, the effect of B7-H3 on
cell migration and invasion was studied in vivo. B7-H3 expression was
significantly higher in the gastric cancer group than that in the normal gaster
group. B7-H3 knockdown by RNA interference decreased cell migration and Transwell
invasion up to 50% in vitro. In the orthotopic transplantation gastric cancer
mouse model, the effect of inhibiting metastasis by knockdown of B7-H3 was
assessed in terms of the average postmortem abdominal visceral metastatic tumor
weight. The results revealed that inhibition of B7-H3 expression reduced gastric
cancer metastasis in vivo. In conclusion, B7-H3 is aberrantly expressed in
gastric cancer. In addition to modulating tumor immunity, B7-H3 may have a novel
role in regulating SGC-7901 cell metastasis.
PMID- 25120099
TI - Genetic characterization and phylogenetic relationships based on 18S rRNA and
ITS1 region of small form of canine Babesia spp. from India.
AB - Canine babesiosis is a vector borne disease caused by intra-erythrocytic
apicomplexan parasites Babesia canis (large form) and Babesia gibsoni (small
form), throughout the globe. Apart from few sporadic reports on the occurrence of
B. gibsoni infection in dogs, no attempt has been made to characterize Babesia
spp. of dogs in India. Fifteen canine blood samples, positive for small form of
Babesia, collected from northern to eastern parts of India, were used for
amplification of 18S rRNA gene (~1665bp) of Babesia sp. and partial ITS1 region
(~254bp) of B. gibsoni Asian genotype. Cloning and sequencing of the amplified
products of each sample was performed separately. Based on sequences and
phylogenetic analysis of 18S rRNA and ITS1 sequences, 13 were considered to be B.
gibsoni. These thirteen isolates shared high sequence identity with each other
and with B. gibsoni Asian genotype. The other two isolates could not be assigned
to any particular species because of the difference(s) in 18S rRNA sequence with
B. gibsoni and closer identity with Babesiaoccultans and Babesiaorientalis. In
the phylogenetic tree, all the isolates of B. gibsoni Asian genotype formed a
separate major clade named as Babesia spp. sensu stricto clade with high
bootstrap support. The two unnamed Babesia sp. (Malbazar and Ludhiana isolates)
clustered close together with B. orientalis, Babesia sp. (Kashi 1 isolate) and B.
occultans of bovines. It can be inferred from this study that 18S rRNA gene and
ITS1 region are highly conserved among 13 B. gibsoni isolates from India. It is
the maiden attempt of genetic characterization by sequencing of 18S rRNA gene and
ITS1 region of B. gibsoni from India and is also the first record on the
occurrence of an unknown Babesia sp. of dogs from south and south-east Asia.
PMID- 25120100
TI - In-silico analysis of claudin-5 reveals novel putative sites for post
translational modifications: Insights into potential molecular determinants of
blood-brain barrier breach during HIV-1 infiltration.
AB - The blood-brain barrier (BBB) poses a huge challenge and is a serious issue in
deciphering the pathophysiology of central nervous system disorders. Endothelial
tight junctions play an essential role in maintaining the integrity of the BBB.
Post-translational modifications (PTMs) in endothelial tight junction proteins
are known to cause deleterious functional impairment and possible disruptions in
BBB integrity. PTMs in tight junction proteins play an important role in human
immunodeficiency virus type 1 (HIV-1) entry through the BBB. Human claudin-5 is
one of the highly expressed brain endothelial tight junction protein and various
PTMs in claudin-5 are expected to aid HIV-1 in crossing the BBB. A precise
characterization of PTMs in claudin-5 is important for understanding its role in
HIV-1 brain infiltration. In this study, we have examined post-translational
crosstalk between phosphorylation, O-glycosylation, palmitoylation and
methylation sites in claudin-5, which could alter claudin-5's ability to maintain
BBB integrity. To the best of our knowledge, this is the first report on claudin
5 protein that suggests a novel interplay between potential PTM sites. PTMs of
predicted residues in claudin-5, suggested in this study, can serve as compelling
targets for potential therapeutic agents against HIV-1 induced neuropathogenesis.
Further site-specific experimental studies in this aspect are highly recommended.
PMID- 25120101
TI - Activated cytotoxic T-lymphocyte immunotherapy is effective for advanced oral and
maxillofacial cancers.
AB - Conventional cancer treatments are surgery, radiotherapy, and chemotherapy, but
treatment efficiency is insufficient and cancer recurrence is common.
Immunotherapy has been added as an important cancer treatment component, but no
reports on its efficacy in oral and maxillofacial cancers exist. We evaluated the
clinical efficacy of adoptive immunotherapy using ex vivo-activated cytotoxic T
lymphocytes (CTL) in the treatment of 7 patients with advanced oral and
maxillofacial cancers with stage IV disease at diagnosis. The mean follow-up
period was 26.2 months. Phenotype of the lymphocyte assay revealed that the
percentage of CD4(+) T cells decreased and that of CD8(+) T cells increased among
infused lymphocytes compared to that in unstimulated peripheral blood mononuclear
cells (PBMCs), and infused lymphocytes produced a significantly higher level of
IFN-gamma than PBMCs or tumor cells alone. In a representative patient who
refused surgery tumor regression was confirmed after CTL infusion. Computed
tomography clearly indicated a significant reduction in tumor size followed by
the complete disappearance of the tumor. Histological examination showed that the
cancers in patients receiving CTL therapy were heavily infiltrated with
lymphocytes. The other 2 patients who received CTL therapy as adjuvant therapy
showed neither recurrent disease nor new disease lesions. The 1-year survival
rates showing response and those with progressive disease were 100 and 25%,
respectively. Moreover, no significant adverse reactions were reported during the
study period. CTL therapy remains in the early stages of treatment options, but
it has potential as a valuable treatment and improvement of quality of life for
patients with otherwise incurable cancers.
PMID- 25120103
TI - Determination of psychotropic use in children and adolescents from a prescription
database: methodological issues.
PMID- 25120102
TI - Inhibition of form-deprivation myopia by a GABAAOr receptor antagonist, (1,2,5,6
tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA), in guinea pigs.
AB - PURPOSE: To investigate the effects of the relatively selective GABAAOr receptor
antagonist (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA) on form
deprivation myopia (FDM) in guinea pigs. METHODS: A diffuser was applied
monocularly to 30 guinea pigs from day 10 to 21. The animals were randomized to
one of five treatment groups. The deprived eye received daily sub-conjunctival
injections of 100 MUl TPMPA at a concentration of (i) 0.03 %, ( ii) 0.3 %, or
(iii) 1 %, a fourth group (iv) received saline injections, and another (v) no
injections. The fellow eye was left untreated. An additional group received no
treatment to either eye. Prior to and at the end of the treatment period,
refraction and ocular biometry were performed. RESULTS: Visual deprivation
produced relative myopia in all groups (treated versus untreated eyes, P < 0.05).
The amount of myopia was significantly affected by the drug treatment (one-way
ANOVA, P < 0.0001); myopia was less in deprived eyes receiving either 0.3 % or 1
% TPMPA (saline = -4.38 +/- 0.57D, 0.3 % TPMPA = -3.00 +/- 0.48D, P < 0.01; 1 %
TPMPA = -0.88 +/- 0.51D, P < 0.001). The degree of axial elongation was
correspondingly less (saline = 0.13 +/- 0.02 mm, 0.3 % TPMPA = 0.09 +/- 0.01 mm,
P < 0.01, 1 % TPMPA = 0.02 +/- 0.01 mm, P < 0.001) as was the VC elongation
(saline = 0.08 +/- 0.01 mm, 0.3 % TPMPA = 0.05 +/- 0.01 mm, P < 0.01, 1 % TPMPA =
0.01 +/- 0.01 mm; P < 0.001). ACD and LT were not affected (one-way ANOVA, P >
0.05). One percent TPMPA was more effective at inhibiting myopia than 0.3 % (P <
0.01), and 0.03 % did not appreciably inhibit the myopia (0.03 % TPMPA versus
saline, P > 0.05). CONCLUSIONS: Sub-conjunctival injections of TPMPA inhibit FDM
in guinea pig models in a dose-dependent manner.
PMID- 25120104
TI - Functional profile of a novel modulator of serotonin, dopamine, and glutamate
neurotransmission.
AB - RATIONALE: Schizophrenia remains among the most prevalent neuropsychiatric
disorders, and current treatment options are accompanied by unwanted side
effects. New treatments that better address core features of the disease with
minimal side effects are needed. OBJECTIVES: As a new therapeutic approach, 1-(4
fluoro-phenyl)-4-((6bR, 10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H
pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-butan-1-one (ITI-007) is
currently in human clinical trials for the treatment of schizophrenia. Here, we
characterize the preclinical functional activity of ITI-007. RESULTS: ITI-007 is
a potent 5-HT2A receptor ligand (K i = 0.5 nM) with strong affinity for dopamine
(DA) D2 receptors (K i = 32 nM) and the serotonin transporter (SERT) (K i = 62
nM) but negligible binding to receptors (e.g., H1 histaminergic, 5-HT2C, and
muscarinic) associated with cognitive and metabolic side effects of antipsychotic
drugs. In vivo it is a 5-HT2A antagonist, blocking (+/-)-2,5-dimethoxy-4
iodoamphetamine hydrochloride (DOI)-induced headtwitch in mice with an inhibitory
dose 50 (ID50) = 0.09 mg/kg, per oral (p.o.), and has dual properties at D2
receptors, acting as a postsynaptic D2 receptor antagonist to block D-amphetamine
hydrochloride (D-AMPH) hyperlocomotion (ID50 = 0.95 mg/kg, p.o.), yet acting as a
partial agonist at presynaptic striatal D2 receptors in assays measuring striatal
DA neurotransmission. Further, in microdialysis studies, this compound
significantly and preferentially enhances mesocortical DA release. At doses
relevant for antipsychotic activity in rodents, ITI-007 has no demonstrable
cataleptogenic activity. ITI-007 indirectly modulates glutamatergic
neurotransmission by increasing phosphorylation of GluN2B-type N-methyl-D
aspartate (NMDA) receptors and preferentially increases phosphorylation of
glycogen synthase kinase 3beta (GSK-3beta) in mesolimbic/mesocortical dopamine
systems. CONCLUSION: The combination of in vitro and in vivo activities of this
compound support its development for the treatment of schizophrenia and other
psychiatric and neurologic disorders.
PMID- 25120106
TI - Potential sensitivity of bias analysis results to incorrect assumptions of
nondifferential or differential binary exposure misclassification.
AB - BACKGROUND: Results of bias analyses for exposure misclassification are dependent
on assumptions made during analysis. We describe how adjustment for
misclassification is affected by incorrect assumptions about whether sensitivity
and specificity are the same (nondifferential) or different (differential) for
cases and noncases. METHODS: We adjusted for exposure misclassification using
probabilistic bias analysis, under correct and incorrect assumptions about
whether exposure misclassification was differential or not. First, we used
simulated data sets in which nondifferential and differential misclassification
were introduced. Then, we used data on obesity and diabetes from the National
Health and Nutrition Examination Survey (NHANES) in which both self-reported
(misclassified) and measured (true) obesity were available, using literature
estimates of sensitivity and specificity to adjust for bias. The ratio of odds
ratio (ROR; observed odds ratio divided by true odds ratio) was used to quantify
magnitude of bias, with ROR = 1 signifying no bias. RESULTS: In the simulated
data sets, under incorrect assumptions (eg, assuming nondifferential
misclassification when it was truly differential), results were biased, with RORs
ranging from 0.18 to 2.46. In NHANES, results adjusted based on incorrect
assumptions also produced biased results, with RORs ranging from 1.26 to 1.55;
results were more biased when making these adjustments than when using the
misclassified exposure values (ROR = 0.91). CONCLUSIONS: Making an incorrect
assumption about nondifferential or differential exposure misclassification in
bias analyses can lead to more biased results than if no adjustment is performed.
In our analyses, incorporating uncertainty using probabilistic bias analysis was
not sufficient to overcome this problem.
PMID- 25120105
TI - Etazolate, a phosphodiesterase-4 enzyme inhibitor produces antidepressant-like
effects by blocking the behavioral, biochemical, neurobiological deficits and
histological abnormalities in hippocampus region caused by olfactory bulbectomy.
AB - RATIONALE: Olfactory bulbectomy (OBX) is a widely used model for antidepressant
screening and known to induce neurodegeneration in several brain areas. Our
earlier studies demonstrated that etazolate produced antidepressant-like effects
in behavioral despair models of depression; however, the potential role of
etazolate on behavior and morphological changes in the hippocampus region along
with its underlying mechanism(s) following OBX has not been adequately addressed.
OBJECTIVES: We evaluated if etazolate could protect against OBX-induced
depression-like behavioral deficits and neurodegeneration. The possible
underlying mechanism of etazolate in OBX model was also investigated. METHODS:
The effects of etazolate were measured in a battery of behavioral paradigms,
including the forced swim test (FST), sucrose consumption, open arm activity in
elevated plus maze (EPM), and hyperemotionality tests. The underlying mechanisms
were investigated by measuring serum corticosterone (CORT), cyclic adenosine
monophosphate (cAMP), cAMP response element binding protein (CREB), brain-derived
neurotrophic factor (BDNF), and oxidative/nitrosative stress (lipid peroxidation
and nitrite) levels and antioxidant enzymes, like reduced glutathione (GSH),
superoxide dismutase (SOD), and catalase (CAT) levels in the hippocampus. RESULT:
OBX rats showed depression-like behavior anomalies in behavioral paradigms. OBX
rats also showed high CORT and decreased cAMP, phosphorylated CREB (pCREB), and
BDNF levels. Additionally, we found increased oxidative/nitrosative stress and
reduced antioxidant enzyme levels in the hippocampus. Histopathological analysis
showed morphological changes and neuronal loss in the hippocampus. Etazolate (0.5
and 1 mg/kg) attenuated the OBX-induced behavioral, biochemical, neurobiological,
and histopathological alterations. CONCLUSION: The aforesaid results suggest that
etazolate produces an antidepressant-like effect and neuroprotection in OBX,
which is possibly mediated by modulating biochemical and neurobiological markers
in the hippocampus.
PMID- 25120107
TI - Visfatin -948G/T and resistin -420C/G polymorphisms in Egyptian type 2 diabetic
patients with and without cardiovascular diseases.
AB - Diabetes mellitus is one of the main threats to human health in the 21st century.
Visfatin/Nampt and resistin are novel adipokines that have been implicated in the
pathogenesis of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD)
complication. Several genetic studies have shown inconsistent results regarding
association of visfatin/Nampt gene (NAMPT) and resistin gene (RETN) polymorphisms
with T2DM and CVD complications. Here, we investigate whether NAMPT -948G/T and
RETN -420C/G polymorphisms are associated with T2DM, its CVD complications, and
serum adipokines levels in 90 Egyptian diabetic patients (44 without CVD and 46
with CVD) along with 60 healthy control subjects. Higher frequencies of NAMPT
948G/G and RETN -420G/G were observed among T2DM patients compared with controls.
Furthermore, the frequencies of these genotypes were significantly higher in T2DM
patients with CVD than those without CVD. Both NAMPT -948G/G and RETN -420G/G
genotypes and G alleles were significantly associated with T2DM and CVD in
Egyptian diabetic patients. Moreover, serum visfatin/Nampt and resistin levels
were markedly elevated in T2DM patients, with the highest values observed in G/G
genotypes among T2DM patients with CVD. In addition, positive correlations were
observed between plasma adipokines levels and CVD risk factors. In conclusion,
our data suggests that genetic variations in NAMPT -948G/T and RETN -420C/G may
contribute to the disposition for T2DM and its CVD complications in Egyptian
patients. However, further studies with greater sample size should be performed
to verify these results.
PMID- 25120108
TI - Screening older Latinos for dementia in the primary care setting.
AB - The purpose was to compare the Spanish language picture version of the Free and
Cued Selective Reminding Test with Immediate Recall (pFCSRT+IR) and the Mini
Mental State Exam (MMSE) in identifying very mild dementia among Spanish speaking
Latino patients. The tests and an independent diagnostic assessment were
administered to 112 Latino patients free of medically diagnosed dementia from an
urban primary care clinic. Receiver operating characteristic (ROC) curves and the
area under the curve (AUC) were used to examine differences in the operating
characteristics of the pFCSRT+IR and the MMSE. Cut scores were manipulated to
equate sensitivities (specificities) at clinically relevant values to compare
differences in specificities (sensitivities) using the Pearson Chi Square test.
Youden's index was used to select the optimal cut scores. Twenty-four of the 112
primary care patients (21%) received a research dementia diagnosis, indicating a
substantial burden of unrecognized dementia. MMSE scores but not free recall
scores were associated with years of education in patients free of dementia. AUC
was significantly higher for free recall than for MMSE. Free recall performed
significantly better than the MMSE in sensitivity and in specificity. Using
optimal cut scores, patients with impaired free recall were 10 times more likely
to have dementia than patients with intact recall, and patients with impaired
MMSE scores were 4.5 times more likely to have dementia than patients with intact
scores. These results suggest that the Spanish language pFCSRT+IR may be an
effective tool for dementia screening in educationally diverse Latino primary
care populations.
PMID- 25120111
TI - [Mental health services from a public health perspective].
PMID- 25120112
TI - [Mental health care reform: the end or still in progress?].
PMID- 25120109
TI - Exercise in ZDF rats does not attenuate weight gain, but prevents hyperglycemia
concurrent with modulation of amino acid metabolism and AKT/mTOR activation in
skeletal muscle.
AB - PURPOSE: Protein metabolism is altered in obesity, accompanied by elevated plasma
amino acids (AA). Previously, we showed that exercise delayed progression to type
2 diabetes in obese ZDF rats with maintenance of beta cell function and reduction
in hyperglucocorticoidemia. We hypothesized that exercise would correct the
abnormalities we found in circulating AA and other indices of skeletal muscle
protein metabolism. METHODS: Male obese prediabetic ZDF rats (7-10/group) were
exercised (swimming) 1 h/day, 5 days/week from ages 6-19 weeks, and compared with
age-matched obese sedentary and lean ZDF rats. RESULTS: Food intake and weight
gain were unaffected. Protein metabolism was altered in obese rats as evidenced
by increased plasma concentrations of essential AA, and increased muscle
phosphorylation (ph) of Akt(ser473) (187%), mTOR(ser2448) (140%), eIF4E-binding
protein 1 (4E-BP1) (111%), and decreased formation of 4E-BP1*eIF4E complex (75%,
0.01 <= p <= 0.05 for all measures) in obese relative to lean rats. Exercise
attenuated the increase in plasma essential AA concentrations and muscle Akt and
mTOR phosphorylation. Exercise did not modify phosphorylation of S6K1, S6, and 4E
BP1, nor the formation of 4E-BP1*eIF4E complex, mRNA levels of ubiquitin or the
ubiquitin ligase MAFbx. Positive correlations were observed between ph-Akt and
fed circulating branched-chain AA (r = 0.56, p = 0.008), postprandial glucose (r
= 0.42, p = 0.04) and glucose AUC during an IPGTT (r = 0.44, p = 0.03).
CONCLUSION: Swimming exercise-induced attenuation of hyperglycemia in ZDF rats is
independent of changes in body weight and could result in part from modulation of
muscle AKT activation acting via alterations of systemic AA metabolism.
PMID- 25120113
TI - [Primary mental healthcare reform in Quebec and the role and coordination
strategies of general practitioners].
AB - OBJECTIVES: The health and mental health systems in Quebec have recently been
substantially transformed. At the heart of this restructuring, reforms aimed to
strengthen primary care and to better integrate services, which are central
trends internationally. This article summarizes Quebec's primary health and
mental health reforms. It also presents the key role of general practitioners in
the treatment of mental health disorders and their coordination strategies with
the mental health care resources in the province. METHODS: Numerous documents on
the Quebec health and mental health reforms and the international literature on
primary mental health care were consulted for this study. Information on general
practitioner roles in mental health were based on administrative data from the
Regie de l'assurance maladie du Quebec (RAMQ) for all medical procedures
performed in 2006. The data was compared with the results of a survey realized in
the same year with 398 general practitioners in Quebec. Complementary qualitative
data was collected through one hour interviews on a subsample of 60 of those
general practitioners. RESULTS: The central aim of the Quebec healthcare reform
was to improve services integration by implementing local healthcare networks. A
population health approach and a hierarchical service provision were promoted.
For a better access and continuity of care, family medicine groups and network
clinics were also developed. The mental health reform (Action Plan in Mental
Health, 2005-2010) was launched in this general context. It prioritized the
consolidation of primary care and shared-care (i.e. increased networking between
general practitioners and psychosocial workers and psychiatrists) by reinforcing
the role of general practitioners in mental health, developing mental health
interdisciplinary teams in primary care and adding a psychiatrist-respondent
function in each Quebec local healthcare network. In mental health, general
practitioners played a central role as the primary source of care and networking
to other resources either primary or specialized health care services. Between 20
25% of visits to general practitioners are related to mental health problems.
Nearly all general practitioners manage common mental disorders and believed
themselves competent to do so; however, the reverse is true for the management of
serious mental disorders. Mainly general practitioners practiced in silo without
much relation with the mental health care resources. Numerous factors were found
to influence the management of mental health problems: patients' profiles (e.g.
the complexity of mental health problems, concomitant disorders), individual
characteristics of the general practitioners (e.g. informal network, training);
professional culture (e.g. formal clinical mechanisms), the institutional setting
(e.g. multidisciplinary or not) and organizations of services (e.g. policies).
CONCLUSION: Unfortunately, the Quebec health and mental health care reforms have
not been fully implemented yet. Family medicine groups and networks clinics,
primary mental health teams and psychiatrists-respondent are not optimally
operational and therefore, are not having a significant outcome. Support
mechanisms to help implement the reforms were not prioritized. Hindering factors
should be identified and minimized to increase positive changes in the health and
mental health systems. This article concludes on the importance of implementing
continuums of care, especially local healthcare networks and best practices in
mental health. Furthermore, strong strategies to support the implementation of
changes should always accompany sweeping reforms.
PMID- 25120110
TI - The effect of green tea extract supplementation on exercise-induced oxidative
stress parameters in male sprinters.
AB - BACKGROUND: Although research suggests that antioxidant supplementation can
protect against exercise-induced muscle damage and oxidative stress, also delayed
post-exercise muscle recovery and hindered adaptation to training were reported
in the supplemented athletes. PURPOSE: The purpose of the study was to evaluate
the effects of green tea extract (GTE) supplementation on selected blood markers
of oxidative stress and muscle damage in sprinters during preparatory phase of
their training cycle. METHODS: Sixteen sprinters participated in a double-blind,
randomized, placebo (PL)-controlled crossover study, including two 4-week
treatment periods with PL and GTE (980 mg polyphenols daily). The sprinters
performed two repeated cycle sprint tests (RST; 4 * 15 s, with 1-min rest
intervals), after PL and GTE supplementation. Blood was sampled before (at rest),
5 min after RST, and after the 24-h recovery. The activities of superoxide
dismutase (SOD) and glutathione peroxidase were measured in erythrocytes, and
total polyphenols, total antioxidant capacity (TAC), uric acid (UA), albumin
(AL), malondialdehyde (MDA), and creatine kinase (CK) were determined in blood
plasma. RESULTS: Repeated cycle sprint test performed after PL induced an
increase in MDA, TAC, and SOD. Moreover, an increase in UA, AL, and CK was
observed after RST irrespective of experimental conditions (PL, GTE).
Supplementation with GTE caused an increase in total polyphenols and TAC at rest,
and a decrease in MDA and SOD after RST. No significant changes in sprint
performance were noted after GTE, as compared to PL. CONCLUSIONS: Supplementation
with GTE prevents oxidative stress induced by RST in sprinters. Furthermore, GTE
supplementation does not seem to hinder training adaptation in antioxidant enzyme
system. On the other hand, neither prevention of exercise-induced muscle damage,
nor an improvement in sprint performance is noted after GTE administration.
PMID- 25120114
TI - [What's a framework without its frame?].
AB - OBJECTIVE: In 2005, the Quebec Ministry of Health launched a major reform of its
Mental Health services. This reform aimed both the type of services
(collaborative care; community care) and the structure (shift to primary care
venues) in which these services where offered. Any major reform must be supported
by different means. This article will review which means are best suited to do
this and up to what point these where used to support the implementation of the
reform. It will also help in preparing for the upcoming launch of the next Mental
Health Plan of Action by the Quebec Ministry of Health. METHOD: The authors
exchanged on several occasions on their observations and thoughts on the subject.
RESULTS: Any major health reform must be supported by different means. Some are
related to legislation or government policies, but these alone are insufficient.
Others means include academic and continuing development actions, service
accreditation or certification and user participation in policy and
implementation stages of service delivery. CONCLUSION: If some means of support
are easily invested, some are neglected. An effort should be made to use all
available means to support the upcoming Plan of Action. User involvement seems
particularly promising.
PMID- 25120115
TI - [Policies and mental health action plans in OECD: lessons for Quebec?].
AB - OBJECTIVES: The objectives of this research are: 1) to provide a conceptual
framework for analyzing mental health policies; 2) to compare mental health
policies across a sample of OECD jurisdictions; 3) to describe configurations of
mental health policies; 4) to identify practical implications for the Province of
Quebec. METHODS: DESIGN: This research is a comparative synthetic study of
mental health policies. SAMPLING: The web sites of the Ministries of health of
the thirty-four OECD countries and ten Canadian Provinces were searched for
mental health policies proposed within the last fifteen years. Twenty one such
policies (with an English or French version) were retrieved, covering thirteen
OECD countries, six Canadian Provinces and the WHO. ANALYSIS: Content analysis
was performed based on the categories (differentiation, integration, governance)
and sub-categories of the aforementioned conceptual framework. Eight policies
that together cover the variations encountered between all policies were used to
identify typical configurations. RESULTS: A conceptual framework derived from
Parsons' Theory of Social Action posits that social action systems must exhibit a
level of internal differentiation that corresponds to the heterogeneity of their
external environment and also a level of integration that allows them to remain
coherent despite the complexity of their environment. Governance mechanisms help
them maintain an equilibrium between differentiation and integration.In terms of
differentiation, mental health policies exhibit much variation between the needs
and the groups that are prioritized (age, gender, ethnicity, culture, etc.), the
types of interventions that are proposed (promotion, prevention, treatment,
rehabilitation, etc.), the systemic levels at which interventions take place
(society, government as a whole, health care system, organizations, programs,
individuals), and the level of specification and scientific basis of proposed
interventions. In terms of integration, policies promote various mechanisms
belonging to four general categories of increasing effectiveness from
hierarchical separation of mandates, to exchange of information, to collaborative
planning, and to complete structural integration and co-localisation of certain
components (ex. dependence and mental health services). In terms of governance,
policies present program theories of varying explicitness and scientific bases,
and with different emphases on structures, processes or outcomes. Management
models also vary in terms of precision, accountability, financing mechanisms,
information systems, and the importance of clinical governance and quality
improvement.Five configurations of mental health policies are identified (the
public health, the professional, the structural technocratic, the functional
technocratic, and the political), each comprising typical combinations of the
preceding ingredients. CONCLUSION: The current Quebec mental health policy
belongs to the structural technocratic configuration. It specifies fragmented
mental health structures with mild integration mechanisms. In the future, it
should consider improving its public health aspects (inter-sector work on the
determinants of mental health), professional aspects (emphasis on scientific
evidence, clinical governance and quality), and functional aspects (integrated
specialized community mental health and addiction services). But political
factors may prevent it from doing so.
PMID- 25120116
TI - [Reflections and recommendations from Quebec mental health university institutes
on the working paper of the provincial forum for the 2014-2020 Mental Health
Action Plan].
AB - GOAL: Quebec's three mental health university institutes (DMHUI, IUSMM and the
IUSMQ) and the Centre hospitalier universitaire de Sherbrooke submitted a
statement to the provincial consultation forum on the 2014-2020 Mental Health
Action Plan (MHAP), which was held in January 2014 and organized by the Ministere
de la Sante et des Services sociaux (MSSS). This article presents these
institutes' main recommendations. METHOD: Mental health university institutes
deliver a wide and diverse range of services. They know about the challenges of
organizing mental health services and are aware of national and international
trends in the delivery of the best organizational and clinical practices in
mental health. It is therefore as key stakeholders in the mental health care
network that they commented on each component in the working paper. RESULTS: The
proposed orientations are consistent with the 2005-2010 MHAP. The presented
themes clearly reflect current issues, although the guidelines must be more
explicit regarding the vision of how services will be organized in coming years.
These institutes therefore suggest that the following principles be included: the
full exercise of citizenship rights, the organization of services within
integrated networks, performance, continuous improvement and innovation, as well
as a global and integrated vision of health. The complexity of today's problems
requires flexibility, complementarity and continuity of services, particularly
for youth, aboriginals, and people with concomitant disorders. These institutions
therefore stress the importance of prevention, early intervention programs, and
increased support for first-line general practitioners and health care
professionals. They also emphasized that specialized inpatient and outpatient
services should not be neglected. Community services must also be structured
around various levels of support, such as ICM and ACT, as well as around
specialized programs available in hospital outpatient clinics. The development
and transfer of knowledge remain a central issue when it comes to improving the
mental health of the general population. The consolidation of ultra-specialized
services, teaching and research should be included in the next MHAP. Finally, a
global health perspective must go beyond the MSSS framework to become a
governmental and interministerial commitment based on a vision of public mental
health that incorporates the health status of the general population and accounts
for social determinants. CONCLUSION: It is important to have a national plan that
promotes a vision. This plan must be part of an interministerial action plan that
truly supports the full exercise of citizenship rights and the fight against
stigmatization in collaboration with people who use these services and their
families.
PMID- 25120117
TI - [Youth mental health at the cross roads of service organization].
AB - The importance of children and youth mental health is increasingly recognized.
This rapidly developing field cannot be conceptualized as an extension of adult
services to a younger age group and its developmental and organizational
specificities are the object of debate. Reviewing recent literature in this
domain and some preliminary information about the Quebec Mental Health Plan
implementation, this paper addresses some of the questions which structure this
debate in Quebec.Quebec mental health plan has put at the forefront collaboration
among disciplines and partnership among institutions. In spite of having produced
significant improvement in the field, discontinuities in services, which
interfere with an ecosystemic model of care, persist. Recent studies suggest that
the organisational climate which surrounds youth mental health services has a
direct impact on the quality of services and on youth health outcomes. A flexible
management structure, which engages clinicians and health workers, favors
empowerment, minimizes work stress and facilitates partnership, is needed to
foster successful interdisciplinary and intersectorial collaboration. This
collaboration is the cornerstone of youth mental health services.
PMID- 25120118
TI - [The role of the mental health community in an evolving mental health system.
State of knowledge and recommendations].
AB - OBJECTIVES: The objectives of this article are: 1) to trace the history and role
of mental health community organizations (MHCO) in the Quebec mental health
system as well as their specific values and practices; and 2) to examine the
impact of the Quebec Mental Health Plan 2005-2010 on the functioning of community
organizations and their relations with the public healthcare system. METHODS:
This article draws upon writings produced by the principal provincial and
regional community organization associations in Quebec, as well as results of
previous studies related to inter-organizational relations among MHCO. RESULTS:
The Quebec community-based system consists of several successive generations of
the MHCO, each constructed within a particular context. Before 1960, the Canadian
Mental Health Association offered activities for promotion and prevention in
mental health and participated in the development of several MHCO. The 1970s
witnessed the formation of groups aimed at the protection of human rights and the
first alternative resources. During the 1980s and 90s, a proliferation of MHCO
followed upon their formal recognition by the Ministere de la Sante et des
services sociaux (MSSS). These new organizations were established not so much in
opposition, or as an alternative, to the public mental health system, but in
complement with it. By 2012-13, there were 412 MCHO financed by the MSSS offering
services to the population. Roughly half were located in the regions of Montreal,
Monteregie and the Capitale Nationale. The MHCO are distinguished from public
institutions by a number of characteristics: 1) treatment based not on diagnosis
but on the overall situation of the person; 2) shared experience with peers; and
3) empowerment, inviting the person to become involved in decisions concerning
his/her treatment and service use as well as decisions that concern the
functioning of the organization; 4) establishment of more egalitarian
relationships between service users and treating professionals; and 5) rootedness
of the organization within the community. MCHO are grouped at the provincial
level according to their functions, their ideological affinity, and or their
particular mandate, but there is no national classification of community
organizations as yet. The financing of community organizations remains a
principal source of discontent. The MSSS has indicated that the overall financing
of MCHO should correspond to at least 10% of global expenditures for mental
health programming, whereas the actual budget is equivalent to only 8.8%. This
underfunding obliges community organizations to reduce services despite demands
for increased financial assistance, which runs the risk of provoking increased
"revolving door" situations, and the utilization of emergency services in cases
of service users transferred from hospitals to the Health Social Services
Centers, who are in difficulty after losing contact with their service providers
who would otherwise have provided follow-up. As well, MCHO fear the loss of their
autonomy and of being reduced to the role of secondary services in signing these
service agreements. The current reform would represent a step backward for MHCO
in terms of recognition of their expertise. The former consultation structures
have been dispossessed of any real power, decision making now being in the hands
of the regional agency and directors of institutions. Numerous relocations of
personnel have also lead to breaks in contact between MCHO and the public system,
as these relationships were usually informal. CONCLUSIONS: A number of
recommendations emanate from these findings that may permit MHCO to respond more
adequately to the needs of the population served without calling into question
their autonomy: 1) offer more adequate financing, particularly for self-help
groups and organizations offering psychosocial rehabilitation, access to
education and work reintegration; 2) allocate specific services exclusively to
the community-based system in order to avoid duplication in services; 3)
recognize a multiplicity of approaches; and 4) reconstruct appropriate decision
making structures.
PMID- 25120119
TI - [Advanced nursing practice: a must for the quality of care and mental health
services].
AB - New professional legislation and reorganization of mental health services have
had a significant influence on mental health nursing practice. Many nurses have
demonstrated clinical leadership and have been able to adapt their services to
the needs of the population specially in the primary health care setting.
However, many believe that the role of nurses is not sufficiently known and
optimally utilized in mental health services. In this article we take a critical
look at the mental health nursing practice in Quebec and at the essential
requirements for its development. This review aims to: 1) describe current trends
in the changing roles and the modernization of mental health nursing practice in
Quebec, 2) provide an overview of the development of advanced nursing practice
and its impact on the quality of mental health services; 3) clarify the concept
of advanced nursing practice and position its development in Quebec and 4)
propose various strategies for optimizing the role of nurses and their
complementarity with other professionals providing mental health services. This
review presents innovative practices developed by nurses in the context of the
restructuring of mental health services. For example, new nursing roles have been
developed to improve the collaboration with general practitioners groups in
primary care settings and facilitate the evaluation and monitoring of patient
presenting medical and psychological problems. Another interesting innovation was
set up by nurses in developing a new service to allow timely access to integrated
care for patients with substance abuse and mental health problems. The various
testimonies reported in this article illustrate the potential contribution of
these nursing innovations in improving the mental health services in Quebec.
Also, in few countries, the reform of mental health services has been a good time
to recognize this potential. Thus, some countries have repositioned the role of
mental health nurses and supported the development of new models of advanced
practice in mental health. These developments have been particularly significant
in the United States and Australia. In United States, during the 1990s, at least
four models of advanced practice in mental health nursing have been developed
leading to wide variations in the roles, education, job titles, scope of practice
and legal authorizations. Consequently, a consensus model of uniform standards of
practice, accreditation and education has been proposed. This LACE model
(Licensure, Accreditation, Certification, Education) will be in effect in 2015.
Australia has adopted a more systematic approach, unified and progressive to
facilitate the development of advanced mental health nursing practice. Australia
who, through their many publications, retains more attention since a clear
definition of the role of the nurse practitioner in mental health and a legal
framework has been adopted at the national level. The Australian experience and
the finding from studies suggest that mental health nurse practitioners and
nurses who are specialized in mental health have the potential to make a
significant contribution to enhancing access to and quality of mental health care
through flexible an innovative approaches. So there are more and more evidence
and indications that Quebec should invest in enhancing the skills of mental
health nurses through the development of advanced nursing practice and
integration of this new model in primary care. In addition, researches, funded by
the Canadian Services Research Foundation (CHSRF, 2010), shows that the
contribution of advanced nursing practice has never been stronger and there is a
broad consensus to its value for the Canadian health care system (Dicenso.et
Lukosius-Briant, 2010). The implementation of advanced practice nursing role in
mental health is part of best practices required to improve care and mental
health services and should be taken into account in future Action Plan 2014-2020.
PMID- 25120120
TI - [The role of families in the Quebec mental health system].
AB - Purpose. This paper aims to summarize the current situation regarding the role of
families of persons with mental disorders within the mental health system in
Quebec.Methods. We made a research in the most recent and pertinent papers or
books regarding: 1) the history of the family involvement in the mental health
system in Quebec; 2) the present situation of these families and the models that
we can see and 3) identify in recent governmental or research documents
recommendations regarding a greater empowerment of the families in the mental
health system.Results. The research provides a historical perspective to the
roles occupied by families. First the family was described as a causal agent; the
work of the psychoanalyst Freud described the family unit as a source of
conflicts in the areas of affect and sexual dynamics, and which results in the
appearance of psychiatric symptoms. Later, this view of a causal agent came both
from the point of view of genetic and from expressed emotions. In the 70's new
perspectives such as general systems theory (von Bertalanffy, 1968), described
the family as responsive to mental disorder of one of its members rather than a
responsible agent. With the deinstitutionalization movement, the family was
perceived as a source of solutions for persons with mental illness, but also as
persons who can live some burden. This subject became well described and a
several studies reported about adverse effects of caring for a person with mental
disorder on the health, well-being and feeling of caregiver burden. In the 90's,
some government action plans called for the relationship between the family and
the health system as a partnership. Also, families want to be involved in
decisions about care and to be informed about the diagnosis and treatment
options. ( Lefley et Wasow, 1993)A new model developed by FFAPAMM that identifies
three main roles enables to contextualize the current role in the current system.
This model, called CAP lists and describes three roles of families that, if they
are dependent on the past, continue to mingle in our time. These roles
are:Accompanist: the role imposed by being near a person with mental illness
(Fradet, 2012). As an accompanist, the family needs to establish relationships
with health professionals. Accompanists want to be considered by stakeholders and
be respected in their desire to share information and participate in
decisions.Client: this is the role that derives from the accompanist when the
caregiver receives care services for its psychological or physical problems
related to the fact support a sick person.Partner: it is relative to the
involvement (or not) the role of family members in the organization of care. It
is a role of participation and decision-making. In this context, we also speak of
participation in the consultation mechanisms.Recommendations from a Quebec
research project and a report of the Commission on Mental Health of Canada will
consider a future where the needs and aspirations of families will be taken into
account in mental health general services, short term health care, community
mental health services. There are also some guidelines regarding education for
professionals about the needs of families and about changing politics.Conclusion.
There exists in all associations of families of person with mental disorders,
training on topics such as how to behave towards different mental disorders or
aggressiveness near reached. A project of the Douglas Institute has hired a
family member to the emergency room to help families better manage this often
difficult time and to facilitate communication with stakeholders. Another project
called "Learning to come closer without aggression" has helped more than 200
family members undergo training inspired by the Omega approach, which helps them
better manage their own behavior in situations of aggression with their loved
one.
PMID- 25120122
TI - [Mental health services in Australia].
AB - Canada is 1.5 times the size of Australia. Australia's population of 20 million
is located principally on the east coast. Like Canada, the Australia has a
federal system of Government with 5 States and two territories. Each State and
territory has its own legislation on mental health. The federal (Commonwealth)
Government is responsible for health care planning. In addition, the federal
Government subsidizes an insurance program (Medicare) that covers visits to
specialists and family physicians, while provincial governments are involved in
the provision of hospital care and community mental health services. The
Commonwealth government also subsidises the cost of medication through the
Pharmaceutical Benefits Scheme. These funds are supplemented by private health
insurance. Mental health costs account for 6.5 per cent of all health care costs.
Primary care treats the majority of common psychological disorders such as
anxiety or depression, while specialist mental health services concentrate on
those with severe mental illness. There have been 4 national mental health plans
since 1992 with the long term aims of promoting mental health, increasing the
quality and responsiveness of services, and creating a consistent approach to
mental health service system reform among Australian states and territories.
These systematic cycles of planning have first allowed a shift from psychiatric
hospitals to community services, from reliance on psychiatric hospitals as
pivotal to psychiatric care system. Community care budgets have increased, but
overall have decreased with money not following patients; but recent deployment
of federally funded through Medicare access to psychotherapy by psychologists for
common mental disorders in primary care have increased overall budget. Concerns
remain that shift to youth first onset psychosis clinics may come from older long
term psychotic patients, a form of discrimination whilst evidence amount of
excess mortality by cardio-vascular diseases and cancers, and due to poverty,
poor health prevention and primary health care for these patients. From a system
perspective, Australia has been inspired by Canada and created in 2012 its own
mental health commission with a similar leading role for patients and families,
aboriginal people representatives, but also a surveillance of the system with its
own yearly report, like the Quebec Health Commissioner 2012 mental health system
performance report.
PMID- 25120121
TI - [Public participation and civic participation of service users in relation to the
Mental Health Action Plan 2005-2010: their spokesperson function].
AB - CONTEXT: Among the guiding principles of the Mental Health Action Plan 2005-2010
(MHAP) of the Quebec Ministere de la sante et des services sociaux (Health and
Social Services) is the recognition that persons who use mental health services
(consumers) can be active agents of their own individual and collective recovery
journey. In accordance with this principle, the MHAP called for greater
participation of consumers in local, regional and national decision-making bodies
within the network of health and social services in Quebec. OBJECTIVE: The
objectives of this article are to look back on the various forms of consumers'
participation in connection with the MHAP since its enactment, and to better
understand the complexities of being spokespersons through the Actor Network
Theory conceptual framework. METHOD: A scientific literature review was
conducted. Different angles of analysis were used to highlight convergences and
trends based on official governmental publications and ongoing research on
consumers' participation in decision and policy making. It was thought that a
vertical case study approach would offer an historical perspective going back to
the early 1960s to discuss the foundations of an "ideology of participation."
Another way of assessing participation is through a horizontal approach that
would compare the terms of participation implemented from one regional authority
to the other, in order to cover most of the Quebec territory. RESULTS: The MHAP
did not provide clear indicators of how to assess progress made with regards to
greater consumer participation. In some regions of Quebec, this participation was
coordinated by community organizations that designated their representatives. In
other regions, local authorities included consumers on a more individual basis to
give their opinion. As all were not at the same stage in their recovery process,
some were in a position to speak using the "we," while others still needed to
express themselves using the "I." In either case, their function as spokespersons
proved to be a bi-directional function. In one direction, the spokesperson
informed the governmental and institutional stakeholders about the expectations
of consumers and about their daily life realities. In the other way, they were
able to explain and make more intelligible the intricacies of the system with a
lay language, which helped non specialists they encountered to remain informed
partners, even though indirectly. As they shared their experience as
spokespersons with their peers, their peers were able to get a clearer
understanding of the progress made to effectively promote active and effective
participation. The lack of clear expectations and dedicated means to support
participation, induced discrepancies from one region to another, making it
difficult, though, to assess progress made overall. CONCLUSION: As the function
of spokesperson got more professionalized with increased opportunities to
participate in policy and decision-making, spokespersons spoke from an "us"
rather than an "I" standpoint. The concept of public participation evolved to one
of civic participation, with the possibility to transcend the "us" and "them"
dichotomy, as members of a community are all citizens to one another. Still, the
terms and conditions of participation could be better defined and more
predictable for greater equity in terms of access to different levels of policy
and decision-making.
PMID- 25120123
TI - [A global reform of mental health care based on a community approach: the Belgian
experience].
AB - The developments in mental health care in Belgium over the last few years show
that some major steps are already taken towards implementing community oriented
care. In Belgium, we are going through a historic moment, as the proposed reform
is ambitious but also complex. Indeed we talk here about a comprehensive mental
health care reform which brings together federal, regional and community
competencies.It aims to transform part of hospital care into community oriented
care by e.g. creating mobile teams in the existing community care mechanisms.In
the same time we are developing an operational approach to networking focusing on
the needs of care users and of their families.In this paper, we will describe the
content of the reform, its mechanisms and all care professionals involved. We
will also present the progress of the exploratory phase by stressing not only
positive aspects that highlight the evolving nature of our approach, but also the
difficulties we are facing in implementing it.
PMID- 25120124
TI - [The effect of age, gender and socioeconomic status on the use of services for
psychological distress symptoms in the general medical sector: Results from the
ESA research program on mental health and aging].
AB - OBJECTIVES: The objective of this study was, first, to document the psychometric
characteristics of a measure of the older adults' socioeconomic status and,
secondly, to test the effect of the socioeconomic status on the association
between the older adults perceived need to improve their mental health and their
use of services in the general medical sector for psychological distress symptoms
taking into account the effect of age and gender. METHOD: Data used in this study
come from the ESA study (Enquete sur la sante des aines) on mental health and
aging, conducted in 2005-2008 using a probabilistic sample (n=2811) of the older
adult population aged 65 years and over living at home in Quebec. RESULTS: Our
results showed that a measurement model of the older adults' socioeconomic status
including an individual-level (SES_I) and an area/contextual-level dimension of
socioeconomic deprivation (SES_C) was plausible. The reliability of the SES index
used in the ESA research program was .92. Our results showed that women (b=-.43)
and older people (b=-.16) were more at risk to have a disadvantaged socioeconomic
status. However, our results did not show evidence of a significant association
between the older adults' socioeconomic status, their perception of a need to
improve their mental health and the use of medical services for psychological
distress symptoms in the general medical sector in the older adult population in
Quebec. CONCLUSION: Our results do not support the idea suggested in other
studies that socioeconomic status has an effect on the older adults use of
services for psychological distress symptoms in the general medical sector and
suggest that in a context where medical health services are provided under a
public insurance programme context, the socioeconomic status does not influence
access to services in the general medical sector in the older adult population.
PMID- 25120126
TI - [Evaluating the implementation of involuntary hospitalization procedures: a
profile of people, audits and recommendations].
AB - Since the 1990s, legislative reforms have been undertaken in many Western
countries to reduce involuntary hospitalization. Studies examining fluctuation
rates before and after the legislative reform show a general trend toward an
increase rather than a decrease in involuntary hospitalization rates (de Stefano
& Ducci, 2008). In Quebec, many reports have shown that consent for psychiatric
evaluation and hospitalisation for people who present an imminent danger to
themselves or to others is difficult to obtain due to clinical, legal, and
ethical considerations. To facilitate this process, a new protocol was developed
and implemented following the training of 335 health workers and 85 medical
doctors in 6 hospitals. Our study evaluated this protocol and established a
profile of people who had been hospitalized against their will. Using a
retrospective analysis, we examined the files of 179 patients who underwent a
psychiatric evaluation process during an involuntary hospitalization. This file
analysis allowed us to develop a better profile of these people and determine
whether the required forms were present and how adequately they were filled out
by the professionals. We also conducted a study with the professionals
responsible for applying the new protocol to get a better idea of its
characteristics (relative advantage, compatibility, simplicity, reversibility and
observability) as well as the principles of consent and the obstacles to its
implementation.Our study showed that that half of the patients were diagnosed
with schizophrenia or another psychosis. Fifty-four point two percent (54.2%) of
the patients were males, 79% were single or separated and only 18,4% were
working. At the time of their crisis situation, 30,7% were brought to the
hospital by police officers and 19% were already hospitalized. The remaining
patients were brought in by ambulance, family members or they came in by
themselves. Professional opinion of the new protocol was positive however they
did not rigorously enter the data required in the new forms. The new form was
present in only 51% of files and when consent was given, it was only documented
in 27% of the cases.These results highlight the need to improve the documentation
process given in the protocol. It would be very useful to establish strategies to
obtain this consent in light of the specific characteristics that make up this
subgroup of people who have been hospitalized against their will. Legislation
alone is not enough to invoke a change in the involuntary hospitalisation rate.
The clinical and organisational context must also be actively prepared to receive
this new practice. In order to do this, evaluative research could contribute to
improving the level of implementation and be of benefit to people in crisis and
those with mental disorders.
PMID- 25120125
TI - [Attitudes of general physicians and family medicine residents towards patients
with borderline personality disorder].
AB - OBJECTIVES: Several studies suggest that health professionals show negative
attitudes towards people with Borderline Personality Disorder (BPD). Many
publications have focused on the attitudes of nurses or other type of clinicians
like social workers or psychologists. Few researches concern the attitudes of
general physicians towards BPD even if they are the main professionals involved
in the evaluation and treatment of these patients. Additionally, patients with
BPD frequently consult general physicians and, because of the difficulties
interacting with these patients, they do not always receive the treatments
required by their condition. This research aims to assess the attitudes of
general physicians and family medicine residents regarding patients presenting
with this disorder. METHOD: Forty family medicine residents and thirty-five
general physicians were compared to thirty-nine mental health professionals using
the Attitudes toward people with BPD Scale (ABPDS; Bouchard, 2001). This measure
has two subscales labeled Comfort when interacting with someone who has BPD and
Positives perceptions about BPD. The internal consistency of the scale as well as
the two distinct factors are satisfactory. The participants also complete a socio
demographic questionnaire. Means, t tests, ANOVAs and factorial ANOVAs are
completed in order to compare the three groups on the ABPDS and explore the
influence of variables such as sex, age, years of experience, and professional
setting (urban or rural) on the results. RESULTS: The results show that general
physicians have similar attitudes than mental health professionals towards people
presenting with BPD and that family medicine residents present less positive
attitude than the other two groups. In addition, clinicians with less experience
tend to have less positive attitudes towards people with BPD and clinicians from
urban settings seem to have more positive attitude. It was difficult to
determinate which variables influence the results because the years of
experience, the professional settings and the title of the participants are
extremely related. The factorial ANOVAs show no interaction effect between these
three variables. CONCLUSION: Several studies show that health professionals
present negative attitudes toward patients with BPD. This study reveals that
general physicians and family medicine residents show respectively similar
attitudes or less positive attitudes than other mental health professionals.
These results underline the importance of providing specific training about BPD
to family medicine residents. Because general physicians guide the evaluations
and interventions concerning these patients and mental health professionals
interact regularly with BPD, it will be helpful if all the clinicians receive
more specific training regarding this disorder.
PMID- 25120127
TI - [For us, being full citizens means...].
AB - OBJECTIVE: One of the four main chapters of the consultation document proposed by
the Quebec Ministere de la sante et des services sociaux (Health and Social
Services), in preparation for the National Forum on the Mental Health Action Plan
2014-2020, is dedicated to the full exercise of citizenship. This paper reports
the dialogue that took place between the CEO of a university mental health
institute and a group of service users, in order to participate in the
consultation process regarding the full exercise of citizenship. METHOD: Since
May 2013, a dozen service users have gathered in the Projet citoyen at the
Research Centre of Institut universitaire en sante mentale de Montreal (IUSMM).
The Projet citoyen is a culturally adapted transposition, in Quebec, of the
Citizens Project that is in place in New Haven, Connecticut. One of the key
components of both the Projet citoyen and the Citizens Project interventions is a
group training regarding citizenship. Participants discuss what it means for them
to be full citizens and they support each other in achieving personal or
collective goals. To assess progress made in such matters, a new Citizenship
Measurement has been developed by the Yale Program for Recovery & Community
Health, and translated into French. This Mesure de la citoyennete is in the
process of being validated; peer research assistants conducted data collection by
asking 178 people who use the mental health services of Quebec to complete the
French Mesure de la citoyennete. The preliminary results of a statistical
analysis were used to structure the dialogue between the IUSMM CEO and the
participants of the Projet citoyen. RESULTS: Three sub-scales emerged from
preliminary statistical analysis (clusters). Colleagues of the Projet citoyen
were invited, through a focus group conducted by one of them, to give evocative
labels to these sub-scales. Regarding the first one, we felt that it was about
asking ourselves what we can bring to others' lives, wondering how we, as members
of the community, can make a difference for a more inclusive civic cohabitation.
The label "contribution to the community" was chosen. For the second sub-scale,
personal and social spheres emerged as both being essential to the achievement of
full citizenship. These spheres must be respected in complementarity. Hence we
chose the label: "personal and social integrity." Finally, the third sub-scale
seemed to combine items that have the common elements of respecting human rights,
respecting the person, and respecting the autonomy of the person. "Rights and
freedom of choice" was chosen as a label for that sub-set. The IUSMM CEO immersed
herself in the Projet citoyen and as her dialogue with the participants deepened
around these features, a sense of mutual respect and friendliness got stronger.
Participants were pleasantly surprised to see that an influential CEO can be
sensitive and comfortable expressing this sensitivity, even with her emotions
while interacting with service users as they are exercising their own citizenship
as research colleagues. CONCLUSION: This case study illustrates a way of
triangulating qualitative and quantitative data sets generated from a
participatory-action research project for which people who use mental health
services have been active research partners throughout. A mobilizing effect was
found among participants of the Projet citoyen who become multipliers once back
in their respective communities and neighborhoods. This effect can also affect a
senior manager. The ISUMM CEO was inspired to relay and communicate this
innovative thinking on the full exercise of citizenship as a governmental
priority in mental health. It could thus be recommended to implement and network
some Projets citoyens in other educational, research and clinical settings. This
would provide opportunities for service users to contribute to the community -
here, the scientific community. It would exemplify respect for personal and
social integrity by channeling the expression of the lived experience into an
instrument of change. These Projets citoyens would advocate for the rights and
freedom of choice of service users as partners, in action, of a citizenship
oriented mental health system.
PMID- 25120129
TI - On the formation of the porous structure in nanostructured a-Si coatings
deposited by dc magnetron sputtering at oblique angles.
AB - The formation of the porous structure in dc magnetron sputtered amorphous silicon
thin films at low temperatures is studied when using helium and/or argon as the
processing gas. In each case, a-Si thin films were simultaneously grown at two
different locations in the reactor which led to the assembly of different porous
structures. The set of four fabricated samples has been analyzed at the
microstructural level to elucidate the characteristics of the porous structure
under the different deposition conditions. With the help of a growth model, we
conclude that the chemical nature of the sputter gas not only affects the
sputtering mechanism of Si atoms from the target and their subsequent transport
in the gaseous/plasma phase towards the film, but also the pore formation
mechanism and dynamics. When Ar is used, pores emerge as a direct result of the
shadowing processes of Si atoms, in agreement with Thornton's structure zone
model. The introduction of He produces, in addition to the shadowing effects, a
new process where a degree of mobility results in the coarsening of small pores.
Our results also highlight the influence of the composition of sputtering gas and
tilt angles (for oblique angle deposition) on the formation of open and/or
occluded porosity.
PMID- 25120128
TI - Systemic oxygenation weakens the hypoxia and hypoxia inducible factor 1alpha
dependent and extracellular adenosine-mediated tumor protection.
AB - Intratumoral hypoxia and hypoxia inducible factor-1alpha (HIF-1-alpha)-dependent
CD39/CD73 ectoenzymes may govern the accumulation of tumor-protecting
extracellular adenosine and signaling through A2A adenosine receptors (A2AR) in
tumor microenvironments (TME). Here, we explored the conceptually novel
motivation to use supplemental oxygen as a treatment to inhibit the hypoxia/HIF
1alpha-CD39/CD73-driven accumulation of extracellular adenosine in the TME in
order to weaken the tumor protection. We report that hyperoxic breathing (60 %
O2) decreased the TME hypoxia, as well as levels of HIF-1alpha and downstream
target proteins of HIF-1alpha in the TME according to proteomic studies in mice.
Importantly, oxygenation also downregulated the expression of adenosine
generating ectoenzymes and significantly lowered levels of tumor-protecting
extracellular adenosine in the TME. Using supplemental oxygen as a tool in
studies of the TME, we also identified FHL-1 as a potentially useful marker for
the conversion of hypoxic into normoxic TME. Hyperoxic breathing resulted in the
upregulation of antigen-presenting MHC class I molecules on tumor cells and in
the better recognition and increased susceptibility to killing by tumor-reactive
cytotoxic T cells. Therapeutic breathing of 60 % oxygen resulted in the
significant inhibition of growth of established B16.F10 melanoma tumors and
prolonged survival of mice. Taken together, the data presented here provide proof
of principle for the therapeutic potential of systemic oxygenation to convert the
hypoxic, adenosine-rich and tumor-protecting TME into a normoxic and
extracellular adenosine-poor TME that, in turn, may facilitate tumor regression.
We propose to explore the combination of supplemental oxygen with existing
immunotherapies of cancer. KEY MESSAGES: Oxygenation decreases levels of tumor
protecting hypoxia. Oxygenation decreases levels of tumor protecting
extracellular adenosine. Oxygenation decreases expression of HIF-1alpha dependent
tumor-protecting proteins. Oxygenation increases MHC class I expression and
enables tumor regression.
PMID- 25120130
TI - Closed-tube human leukocyte antigen DQA1*05 genotyping assay based on switchable
lanthanide luminescence probes.
AB - Genotyping in closed tube is commonly performed using polymerase chain reaction
(PCR) amplification and allele-specific oligonucleotide probes using fluorescence
resonance energy transfer (FRET). Here we introduce a homogeneous human leukocyte
antigen (HLA)-DQA1*05 end-point PCR assay based on switchable lanthanide
luminescence probe technology and a simple dried blood sample preparation. The
switchable probe technology is based on two non-luminescent oligonucleotide
probes: one carrying a non-luminescent lanthanide chelate and the other carrying
a light-absorbing antenna ligand. Hybridization of the probes in adjacent
positions to the target DNA leads to the formation of a highly luminescent
lanthanide chelate complex by self-assembly of the reporter molecules.
Performance of the HLA-DQA1*05 assay was evaluated by testing blood samples
collected on sample collection cards and was prepared by lysing the punched
samples (3-mm discs) using alkaline reaction conditions and high temperature.
Testing of 147 blood samples yielded 100% correlation to the heterogeneous DELFIA
technology-based reference assay. Genotyping requires carefully designed probe
sequences able to discriminate matched and mismatched target sequences by
hybridization. Furthermore, definite genotype discrimination was achieved because
inherently non-luminescent switchable probes together with time-resolved
measurement mode led to very low background signal level and, therefore, very
high signal differences averaging 54-fold between DQA1*05 and other alleles.
PMID- 25120131
TI - Combining stress-only myocardial perfusion imaging with coronary calcium scanning
as a new paradigm for initial patient work-up: an exploratory analysis.
AB - BACKGROUND: We conducted an exploratory analysis to test whether the addition of
a CAC scan can increase the applicability of stress-only SPECT-MPI. METHODS: We
studied 162 patients referred for rest/stress SPECT-MPI who underwent a CAC scan.
Each scan was interpreted by two readers in stepwise fashion: stress-only images;
addition of clinical data; and addition of CAC data. At each step, the reader was
asked if rest SPECT-MPI was necessary. RESULTS: Stress-only images were
interpreted as normal in 62, probably normal in 42, equivocal in 15, probably
abnormal in 5, and definitely abnormal in 38 patients. Rest SPECT-MPI imaging was
considered necessary, in 0% of normal studies, but in 88% of probably normal
studies, and 100% of those with equivocal/abnormal studies. Addition of the
clinical data did not materially change this decision. Additional consideration
of the CAC scan results did not influence the deemed lack of need for a rest
SPECT-MPI with normal SPECT-MPI or the necessity of rest SPECT-MPI with abnormal
SPECT-MPI. However, the CAC scan reduced the deemed need for a rest SPECT-MPI in
72% with a probably normal, 47% with an equivocal, and 40% of those with a
probably abnormal SPECT-MPI. CONCLUSIONS: Our exploratory analysis indicates that
addition of a CAC scan to stress SPECT-MPI tends to diminish experienced readers'
deemed need to perform rest SPECT-MPI studies among patients with probably normal
or borderline stress-only SPECT-MPI studies. Thus, further study appears
warranted to assess the utility of using CAC scanning as a means for increasing
the percent of SPECT-MPI studies that can be performed as stress-only studies.
PMID- 25120133
TI - Phase analysis of myocardial SPECT to understand mechanisms of disease and
therapy.
PMID- 25120134
TI - Are absolute myocardial blood flow PET measurements ready for clinical use?
PMID- 25120132
TI - Data-driven respiratory motion tracking and compensation in CZT cameras: a
comprehensive analysis of phantom and human images.
AB - BACKGROUND: This study described a method for tracking and compensating
respiratory motion in cadmium-zinc-telluride (CZT) cameras. We evaluated motion
effects on myocardial perfusion imaging and assessed the usefulness of motion
compensation in phantom and clinical studies. METHODS: SPECT studies were
obtained from an oscillating heart phantom and 552 patients using CZT cameras
with list-mode acquisition. Images were reformatted in 500-ms frames, and the
activity centroid was calculated as respiratory signal. The myocardial perfusion,
left ventricular (LV) wall thickness, and LV volume were assessed before and
after the motion compensation technique. RESULTS: In phantom studies, we
documented only minimal bias between simulated and measured shifts. Significantly
reduced tracer activity, increased wall thickness and decreased volume in scans
with 15 mm or more axial shifts were noted. In clinical studies, there was a
higher prevalence of significant motion after treadmill exercise. The motion
compensation technique could successfully compensate those motion artifacts.
CONCLUSION: The described method allows for tracking and compensating respiratory
motion in CZT cameras. Significant respiratory motion is still not uncommon using
CZT cameras, especially in patients who underwent treadmill tests. Motion
blurring can be compensated using image processing techniques and image quality
could be significantly improved.
PMID- 25120136
TI - Training in time-limited dynamic psychotherapy: A systematic comparison of pre-
and post-training cases treated by one therapist.
AB - OBJECTIVE: This qualitative study systematically compared cases treated by the
same therapist in order to understand the group comparison findings of a larger
study on training of experienced therapists (the "Vanderbilt II" psychotherapy
project). METHOD: The therapist, Dr C., was selected based on the therapist's
overall treatment successes. His two patients were selected based on their
outcomes and the relative training cohort from which they were drawn: a case with
successful outcome from the pre-training cohort and a case of negligible
improvement from the post-training cohort. RESULTS: Dr C. demonstrated a variety
of interpersonal skills throughout his pre-training case, though there was also
poor interpersonal process throughout. However, in the second case he had
considerable difficulty in adapting his typical therapeutic approach to the
requirements of the time-limited dynamic psychotherapy (TLDP) manual, even while
appearing to work hard to find ways to use the manual. CONCLUSIONS: Dr C.'s
spontaneity, and his unique set of interpersonal skills may enhanced his initial
rapport and alliance building with clients and yet may not have interfaced well
with TLDP. His unique interpersonal skills also may have contributed to problems
of interpersonal process. Future research may benefit from examining the
interaction of between therapist interpersonal skills and the implementation of
the treatment manual.
PMID- 25120138
TI - Chemical-assisted femtosecond laser writing of lab-in-fibers.
AB - The lab-on-chip (LOC) platform has presented a powerful opportunity to improve
functionalization, parallelization, and miniaturization on planar or multilevel
geometries that has not been possible with fiber optic technology. A migration of
such LOC devices into the optical fiber platform would therefore open the
revolutionary prospect of creating novel lab-in-fiber (LIF) systems on the basis
of an efficient optical transport highway for multifunctional sensing. For the
LIF, the core optical waveguide inherently offers a facile means to interconnect
numerous types of sensing elements along the optical fiber, presenting a radical
opportunity for optimizing the packaging and densification of diverse components
in convenient geometries beyond that available with conventional LOCs. In this
paper, three-dimensional patterning inside the optical fiber by femtosecond laser
writing, together with selective chemical etching, is presented as a powerful
tool to form refractive index structures such as optical waveguides and gratings
as well as to open buried microfluidic channels and optical resonators inside the
flexible and robust glass fiber. In this approach, optically smooth surfaces (~12
nm rms) are introduced for the first time inside the fiber cladding that
precisely conform to planar nanograting structures when formed by aberration-free
focusing with an oil-immersion lens across the cylindrical fiber wall. This
process has enabled optofluidic components to be precisely embedded within the
fiber to be probed by either the single-mode fiber core waveguide or the laser
formed optical circuits. We establish cladding waveguides, X-couplers, fiber
Bragg gratings, microholes, mirrors, optofluidic resonators, and microfluidic
reservoirs that define the building blocks for facile interconnection of inline
core-waveguide devices with cladding optofluidics. With these components, more
advanced, integrated, and multiplexed fiber microsystems are presented
demonstrating fluorescence detection, Fabry-Perot interferometric refractometry,
and simultaneous sensing of refractive index, temperature, and bending strain.
The flexible writing technique and multiplexed sensors described here open
powerful prospects to migrate the benefits of LOCs into a more flexible and
miniature LIF platform for highly functional and distributed sensing
capabilities. The waveguide backbone of the LIF inherently provides an efficient
exchange of information, combining sensing data that are attractive in telecom
networks, smart catheters for medical procedures, compact sensors for security
and defense, shape sensors, and low-cost health care products.
PMID- 25120137
TI - Resveratrol attenuates hypoxia/reoxygenation-induced Ca2+ overload by inhibiting
the Wnt5a/Frizzled-2 pathway in rat H9c2 cells.
AB - Resveratrol is able to protect myocardial cells from ischemia/reperfusion-induced
injury. However, the mechanism has yet to be fully elucidated. In the present
study, it is reported that resveratrol has a critical role in the control of Ca2+
overload, which is the primary underlying cause of ischemia/reperfusion injury.
Hypoxia/reoxygenation (H/R) treatment decreased the cell viability and increased
the apoptosis of H9c2 cells, whereas the caspase-3 and intracellular Ca2+ levels
were greatly elevated compared with the control group. Treatment of H9c2 cells
with resveratrol (5, 15 and 30 uM) reduced caspase-3 expression and cardiomyocyte
apoptosis in a dose-dependent manner, and the intracellular Ca2+ overload was
also significantly decreased. Furthermore, Frizzled-2 and Wnt5a belong to the non
canonical Wnt/Ca2+ pathway, which have been demonstrated to be responsible for
Ca2+ overload, and were thus detected in the present study. The results indicated
that both the mRNA and protein expression levels of Frizzled-2 and Wnt5a in H/R
induced H9c2 cells were markedly increased compared with the levels found in
normal cells, and treatment with resveratrol (5, 15 and 30 uM) significantly
reduced the expression of Frizzled-2 and Wnt5a compared with the H/R group. The
results indicated that resveratrol protected myocardial cells from H/R injury by
inhibiting the Ca2+ overload through suppression of the Wnt5a/Frizzled-2 pathway.
PMID- 25120135
TI - HIV and Stem Cell Transplantation.
AB - In human immunodeficiency virus (HIV)-infected persons, the incidence of
hematologic malignancies, including leukemia and lymphoma, is increased despite
the use of successful antiretroviral therapy. Hematopoietic stem cell
transplantation (SCT) is emerging as a safe and effective therapy for HIV
infected persons with hematologic malignancies. Management of these patients is
complicated by drug-drug interactions involving antiretroviral therapy (ART) that
may impact conditioning agent efficacy and metabolism of immunosuppressive
medications and potentiate drug toxicities. As such, optimal strategies for ART
remain controversial. We discuss recent advances, controversies, and future
directions related to SCT in HIV-infected persons, including the investigation of
allogeneic SCT as a strategy for HIV cure.
PMID- 25120139
TI - Immunohistological examination of a skin lesion in a Japanese case with hand,
foot and mouth disease caused by coxsackie-virus A6.
PMID- 25120143
TI - From epidemiology and genetics to diagnostics, outcome measures, and novel
treatments in autoimmune bullous diseases.
PMID- 25120144
TI - Proteomic revelations.
AB - The power of proteomics in cultured skin fibroblasts from individuals with either
systemic sclerosis or recessive dystrophic epidermolysis bullosa has led to the
common finding of senescence and deficiencies in autophagy. Both of these
disorders exert high demand on fibroblast activity, and without the protective
action of autophagy cellular stress could have many adverse effects that are
further amplified by the senescent phenotype.
PMID- 25120145
TI - The virtues of oxygenation: low tissue oxygen adversely affects the killing of
Leishmania.
AB - Hypoxia contributes to the persistence of infections through altered immune
responses. Studies examining skin O2 changes at the site of a lesion are limited.
The prevailing methods require the use of electrochemical O2 sensors or
radiolabeled electrodes that utilize O2 and may interfere with the precision at
low O2 levels. In this issue, Mahnke et al. (2014) demonstrate, using a novel
fluorescence-based imaging technology, that low oxygen tension (pO2) impairs NO
mediated anti-leishmanial immunity, leading to increased parasite burden.
Replenishing tissue oxygen profoundly enhanced NO-mediated leishmanial killing,
underscoring the need to accurately assess oxygenation in infected tissues as a
novel strategy to challenge intracellular infection. The technology presented
here may have clinical-translational potential in noninvasively assessing disease
burden and response to treatment.
PMID- 25120146
TI - A new player on the psoriasis block: IL-17A- and IL-22-producing innate lymphoid
cells.
AB - Innate lymphoid cells (ILCs) are a recently discovered family of innate immune
cells belonging to the lymphoid lineage, yet lacking antigen-specific receptors.
ILCs were first identified in the intestinal tract, where they contribute to
epithelial barrier integrity and host responses to commensal microbes. Teunissen
et al. (in the current issue) and Villanova et al. (2014) now suggest an
important role for type 3 ILCs (ILC3s) in the skin, particularly in psoriasis.
Both groups found an increased frequency of IL-22- and/or IL-17A-producing ILCs
in psoriatic skin and blood. These cells are activated in response to IL-1beta
and IL-23, correlate with disease severity, and are decreased following antitumor
necrosis factor-alpha (anti-TNFalpha) treatment. The presence of a novel ILC
population in psoriatic skin, one that responds to biologic therapeutics,
suggests that dysregulation of ILCs is a contributing factor to psoriasis
pathogenesis.
PMID- 25120147
TI - Gene regulation at a distance: higher-order chromatin folding and the coordinated
control of gene transcription at the epidermal differentiation complex locus.
AB - Chromatin structure and spatial interactions between proximal and distal gene
regulatory elements, including gene core promoters and enhancers, are important
in the control of gene transcription. In this issue, Oh et al. characterized an
AP-1-dependent enhancer at the epidermal differentiation complex locus that
establishes spatial interactions with numerous gene promoter regions at that
locus.
PMID- 25120148
TI - Keratinocyte growth regulation TRP-ed up over downregulated TRPV4?
AB - This commentary on an exciting new study (Fusi et al., 2014) puts the finding of
TRPV4 downregulation in several nonmelanoma skin cancers into context. The
original paper point toward possible use of TRPV4 as dermatopathologic marker,
also toward the possibility that downregulated TRPV4 can affect biological
properties of the cancer, by enhancing, but also regulating tumor growth. As
calcium-permeable TRPV4 has recently been identified as UVB-receptor in skin
keratinocytes, where it regulates skin tissue injury and pain after UVB
overexposure, it is discussed whether TRPV4 downregulation can also be found in
other non-UVB-exposed cancers.
PMID- 25120149
TI - Augmentation of cutaneous wound healing by pharmacologic mobilization of
endogenous bone marrow stem cells.
AB - Novel therapeutic tools to accelerate wound healing would have a major impact on
the overall burden of skin disease. Lin et al. demonstrate in mice that
endogenous bone marrow stem cell mobilization, produced by a pharmacologic
combination of AMD3100 and tacrolimus, leads to faster and better-quality wound
healing, findings that have exciting potential for clinical translation.
PMID- 25120150
TI - JID VisualDx Quiz: September 2014.
PMID- 25120151
TI - Tissue microarray.
PMID- 25120152
TI - Cells to surgery quiz: September 2014.
PMID- 25120153
TI - Dental knowledge and attitude toward school dental-health programs among parents
of kindergarten children in Winterthur.
AB - The current study investigated the attitudes and knowledge regarding diet and
oral hygiene of parents with kindergarten children. The parents' statements were
evaluated in terms of their socioeconomic background and were compared with the
annual clinical examination of the children. The objective of the study was to
assess the effectiveness of the school dental-health program and adapt it to
today's societal needs. Of those who participated in the interview, 61% were
Swiss, 16% were from former Yugoslavia or Turkey, and 12% each from the EU or
other countries. Of the children examined, 39% already had caries, and 18% of
those showed more than two lesions. The parents' knowledge correlated with the
severity of the child's caries as well as with the parents' income, country of
origin, and education. There was a correlation between the child's dental decay
and lower income, as well as lower education and non-Swiss nationality of the
parents. Parents with higher income and better education more often participated
in the preschool's preventive program. Parents from former Yugoslavia or Turkey
participated less frequently than parents from other countries. The study
demonstrated that parents who especially needed instruction and prophylaxis are
contacted too late or not at all through the dental-health program at
kindergarten and that new approaches to prevention should be implemented to more
effectively reach the parents.
PMID- 25120154
TI - Women with osteoarthritis have elevated synovial fluid levels of insulin-like
growth factor (IGF)-1 and IGF-binding protein-3.
AB - The present study explores the possible connection between synovial fluid
concentrations of insulin like growth factor (IGF-1), IGF-binding protein (IGFBP
3), leptin, and C-reactive protein (CRP) in osteoarthritis (OA). Synovial fluid
specimens were obtained from a total of thirty-four individuals with and without
OA. Protein-normalized measurements of IGF-1, IGFBP-3, and leptin concentrations
in synovial fluid showed significantly (P < 0.05) elevated levels in women with
knee OA but not in men. This study provides initial evidence that protein
normalized IGF-1 and IGFBP-3 and leptin levels increase in synovial fluid of
women but not in men with OA versus those without OA.
PMID- 25120155
TI - Hematologic malignancies of the pancreas.
AB - Hematologic malignancies are relatively uncommon neoplasms of abdominal soft
tissue. This article discusses the clinical and imaging features of pancreatic
lymphoma, pancreatic extraosseous multiple myeloma, granulocytic sarcoma
(chloroma), posttransplant lymphoproliferative disorder, and Castleman disease.
The combination of imaging findings and the appropriate clinical presentation
should allow the radiologist to raise a provisional diagnosis of hematologic
malignancy.
PMID- 25120156
TI - Studies of hot photoluminescence in plasmonically coupled silicon via variable
energy excitation and temperature-dependent spectroscopy.
AB - By integrating silicon nanowires (~150 nm diameter, 20 MUm length) with an Omega
shaped plasmonic nanocavity, we are able to generate broadband visible
luminescence, which is induced by high order hybrid nanocavity-surface plasmon
modes. The nature of this super bandgap emission is explored via
photoluminescence spectroscopy studies performed with variable laser excitation
energies (1.959 to 2.708 eV) and finite difference time domain simulations.
Furthermore, temperature-dependent photoluminescence spectroscopy shows that the
observed emission corresponds to radiative recombination of unthermalized (hot)
carriers as opposed to a resonant Raman process.
PMID- 25120157
TI - Development of a PET scanner for simultaneously imaging small animals with MRI
and PET.
AB - Recently, positron emission tomography (PET) is playing an increasingly important
role in the diagnosis and staging of cancer. Combined PET and X-ray computed
tomography (PET-CT) scanners are now the modality of choice in cancer treatment
planning. More recently, the combination of PET and magnetic resonance imaging
(MRI) is being explored in many sites. Combining PET and MRI has presented many
challenges since the photo-multiplier tubes (PMT) in PET do not function in high
magnetic fields, and conventional PET detectors distort MRI images. Solid state
light sensors like avalanche photo-diodes (APDs) and more recently silicon photo
multipliers (SiPMs) are much less sensitive to magnetic fields thus easing the
compatibility issues. This paper presents the results of a group of Canadian
scientists who are developing a PET detector ring which fits inside a high field
small animal MRI scanner with the goal of providing simultaneous PET and MRI
images of small rodents used in pre-clinical medical research. We discuss the
evolution of both the crystal blocks (which detect annihilation photons from
positron decay) and the SiPM array performance in the last four years which
together combine to deliver significant system performance in terms of speed,
energy and timing resolution.
PMID- 25120158
TI - Development of an ELISA and immunochromatographic strip for highly sensitive
detection of microcystin-LR.
AB - A monoclonal antibody for microcystin-leucine-arginine (MC-LR) was produced by
cell fusion. The immunogen was synthesized in two steps. First, ovalbumin/ bovine
serum albumin was conjugated with 6-acetylthiohexanoic acid using a carbodiimide
EDC (1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride)/ NHS (N
hydroxysulfosuccinimide) reaction. After dialysis, the protein was reacted with
MC-LR based on a free radical reaction under basic solution conditions. The
protein conjugate was used for immunization based on low volume. The antibodies
were identified by indirect competitive (ic)ELISA and were subjected to tap water
and lake water analysis. The concentration causing 50% inhibition of binding of
MC-LR (IC50) by the competitive indirect ELISA was 0.27 ng/mL. Cross-reactivity
to the MC-RR, MC-YR and MC-WR was good. The tap water and lake water matrices had
no effect on the detection limit. The analytical recovery of MC-LR in the water
samples in the icELISA was 94%-110%. Based on this antibody, an
immunochromatographic biosensor was developed with a cut-off value of 1 ng/mL,
which could satisfy the requirement of the World Health Organization for MC-LR
detection in drinking water. This biosensor could be therefore be used as a fast
screening tool in the field detection of MC-LR.
PMID- 25120159
TI - A novel carbon nanofibers grown on glass microballoons immunosensor: a tool for
early diagnosis of malaria.
AB - This paper presents a novel method for direct detection of Plasmodium falciparum
histidine rich protein-2 (PfHRP-2) antigen using carbon nanofiber (CNF) forests
grown on glass microballoons (NMBs). Secondary antibodies specific to PfHRP-2
densely attached to the CNFs exhibit extraordinary ability for the detection of
minute concentrations of Plasmodium species. A sandwich immunoassay protocol was
employed, where a glass substrate was used to immobilize primary antibodies at
designated capture zones. High signal amplification was obtained in both
colorimetric and electrical measurements due to the CNFs through specific
binding. As a result, it was possible to detect PfHRP-2 levels as low as 0.025
ng/mL concentration in phosphate buffered saline (PBS) using a visual signal
within only 1 min of test duration. Lower limits of 0.01 ng/mL was obtained by
measuring the electrical resistivity of the capture zone. This method is also
highly selective and specific in identifying PfHRP-2 and other Plasmodium species
from the same solution. In addition, the stability of the labeling mechanism
eliminates the false signals generated by the use of dyes in current malaria
rapid diagnostic test kits (MRDTs). Thus, the rapid, sensitive and high signal
amplification capabilities of NMBs is a promising tool for early diagnosis of
malaria and other infectious diseases.
PMID- 25120160
TI - A catheter-based acoustic interrogation device for monitoring motility dynamics
of the lower esophageal sphincter.
AB - This paper presents novel minimally-invasive, catheter-based acoustic
interrogation device for monitoring motility dynamics of the lower esophageal
sphincter (LES). A micro-oscillator actively emitting sound wave at 16 kHz is
located at one side of the LES, and a miniature microphone is located at the
other side of the sphincter to capture the sound generated from the oscillator.
Thus, the dynamics of the opening and closing of the LES can be quantitatively
assessed. In this paper, experiments are conducted utilizing an LES motility
dynamics simulator. The sound strength is captured by the microphone and is
correlated to the level of LES opening and closing controlled by the simulator.
Measurements from the simulator model show statistically significant (p < 0.05)
Pearson correlation coefficients (0.905 on the average in quiet environment and
0.736 on the average in noisy environment, D.O.F. = 9). Measuring the level of
LES opening and closing has the potential to become a valuable diagnostic
technique for understanding LES dysfunction and the disorders associated with it.
PMID- 25120161
TI - A wireless portable high temperature data monitor for tunnel ovens.
AB - Tunnel ovens are widely used in the food industry to produce biscuits and
pastries. In order to obtain a high quality product, it is very important to
control the heat transferred to each piece of dough during baking. This paper
proposes an innovative, non-distorting, low cost wireless temperature measurement
system, called "eBiscuit", which, due to its size, format and location in the
metal rack conveyor belt in the oven, is able to measure the temperature a real
biscuit experience while baking. The temperature conditions inside the oven are
over 200 degrees C for several minutes, which could damage the "eBiscuit"
electronics. This paper compares several thermal insulating materials that can be
used in order to avoid exceeding the maximum operational conditions (80 degrees
C) in the interior of the "eBiscuit. The data registered is then transmitted to a
base station where information can be processed to obtain an oven model. The
experimental results with real tunnel ovens confirm its good performance, which
allows detecting production anomalies early on.
PMID- 25120162
TI - Flexible capacitive electrodes for minimizing motion artifacts in ambulatory
electrocardiograms.
AB - This study proposes the use of flexible capacitive electrodes for reducing motion
artifacts in a wearable electrocardiogram (ECG) device. The capacitive electrodes
have conductive foam on their surface, a shield, an optimal input bias resistor,
and guarding feedback. The electrodes are integrated in a chest belt, and the
acquired signals are transmitted wirelessly for ambulatory heart rate monitoring.
We experimentally validated the electrode performance with subjects standing and
walking on a treadmill at speeds of up to 7 km/h. The results confirmed the
highly accurate heart rate detection capacity of the developed system and its
feasibility for daily-life ECG monitoring.
PMID- 25120163
TI - A group neighborhood average clock synchronization protocol for wireless sensor
networks.
AB - Clock synchronization is a very important issue for the applications of wireless
sensor networks. The sensors need to keep a strict clock so that users can know
exactly what happens in the monitoring area at the same time. This paper proposes
a novel internal distributed clock synchronization solution using group
neighborhood average. Each sensor node collects the offset and skew rate of the
neighbors. Group averaging of offset and skew rate value are calculated instead
of conventional point-to-point averaging method. The sensor node then returns
compensated value back to the neighbors. The propagation delay is considered and
compensated. The analytical analysis of offset and skew compensation is
presented. Simulation results validate the effectiveness of the protocol and
reveal that the protocol allows sensor networks to quickly establish a consensus
clock and maintain a small deviation from the consensus clock.
PMID- 25120164
TI - Active in-database processing to support ambient assisted living systems.
AB - As an alternative to the existing software architectures that underpin the
development of smart homes and ambient assisted living (AAL) systems, this work
presents a database-centric architecture that takes advantage of active databases
and in-database processing. Current platforms supporting AAL systems use database
management systems (DBMSs) exclusively for data storage. Active databases employ
database triggers to detect and react to events taking place inside or outside of
the database. DBMSs can be extended with stored procedures and functions that
enable in-database processing. This means that the data processing is integrated
and performed within the DBMS. The feasibility and flexibility of the proposed
approach were demonstrated with the implementation of three distinct AAL
services. The active database was used to detect bed-exits and to discover common
room transitions and deviations during the night. In-database machine learning
methods were used to model early night behaviors. Consequently, active in
database processing avoids transferring sensitive data outside the database, and
this improves performance, security and privacy. Furthermore, centralizing the
computation into the DBMS facilitates code reuse, adaptation and maintenance.
These are important system properties that take into account the evolving
heterogeneity of users, their needs and the devices that are characteristic of
smart homes and AAL systems. Therefore, DBMSs can provide capabilities to address
requirements for scalability, security, privacy, dependability and
personalization in applications of smart environments in healthcare.
PMID- 25120165
TI - Dielectric and terahertz spectroscopy of polarizable and nonpolarizable water
models: a comparative study.
AB - Using extensive classical molecular dynamics simulations, we compute the
dielectric and far-infrared spectra of nine popular water models, including
polarizable and nonpolarizable ones. We analyze the dielectric spectra using a
two-relaxation model that allows one to extract the characteristic time of both
the main dielectric relaxation and the fast relaxation. The use of a Cole-Cole
functional form permits also quantitative assessment of the absence of deviations
from the Debye form of the main dielectric peak. In the THz region of the
spectrum, we compute the infrared absorbance caused by molecular libration, which
appears to be qualitatively different for three main groups of molecular models.
The complexity of the librational band is further investigated by decomposing the
spectrum into the contributions of water fractions with a different number of
hydrogen-bonded neighbors.
PMID- 25120166
TI - Subcellular localization of DAXX influence ox-LDL induced apoptosis in
macrophages.
AB - Here we aimed to evaluate the effects of DAXX subcellular localization on ox-LDL
induced macrophages apoptosis. Cytoplasmic localization vector DAXX-W621A and
nuclear localization vector DAXX-S667A were constructed by point mutation in
DAXX. Blank vector, full length DAXX, DAXX-W621A, DAXX-S667A was transfect into
RAW264.7 cells, respectively. Then the cells were incubated with 100 mg/ml ox-LDL
for 48 h. Immunofluorescent assay was used to assay the localization of DAXX. MTT
and Flow cytometry was used to determine cellular viability and apoptosis. RT-PCR
and Western blot were used to analyze the expression levels. A significantly
increased expression of DAXX was found in transfected cells of DAXX. The content
of DAXX in nucleus was significantly increased in DAXX(S667A), and DAXX was
significantly increased in cytoplasm of DAXX(W621A). Besides, we found DAXX was
mainly expressed in nucleus with a low-level expression in cytoplasm through
immunofluorescence. However in DAXX(W621A) group, the DAXX began to transferred
to cytoplasm, which exhibited significant florescence. After treated with ox-LDL,
the cytoactive of DAXX-W621A exhibited significantly decreased level when
compared DAXX group. However, after added inhibitor LMB, the inhibition was
relieved. The cell viability was also significantly increased in DAXX-S667A
group. The results of apoptosis rates were similar in each group. Furthermore, we
found the expression of ASK1 and JNK was also consistent with the apoptosis
rates. Cytoplasmic localization of DAXX can increase injury sensitivity of ox-LDL
on cells, and nuclear localization can antagonise the effect of ox-LDL. Besides,
it is certified ox-LDL induced apoptosis is mainly through ASK1-JNK pathway.
PMID- 25120167
TI - The association between KL polymorphism and prostate cancer risk in Korean
patients.
AB - The Klotho (KL) gene is a classical "aging suppressor" gene. Although recent
studies have shown that KL participates in the progression of several types of
human cancers, the relationship between KL polymorphism and prostate cancer was
unknown. The present study aimed to investigate the association between KL
genetic polymorphisms and prostate cancer. Twenty-five common single nucleotide
polymorphisms (SNPs) in KL gene (including KL gene polymorphism C1818T in exon 4)
were assessed in 272 prostate cancer cases and 173 controls. Single-locus
analyses were conducted using unconditional logistic regression. In addition, we
did a haplotype analysis for the 25 KL SNPs tested. CC genotype of C1548T KL
polymorphism had approximately twofold increased prostate cancer risk compared
with the homozygous genotype TT and heterozygote CT (odds ratio 1.85 [95% CI,
1.09-3.12], P = 0.02). We also found that non-T allele carriers had significantly
higher prostate cancer risk associated with the prostate cancer clinical
characteristics (tumor stage or Gleason score). Our findings suggested that the
C1548T polymorphism of KL gene is associated with the prostate cancer and may act
as a risk factor for the development of prostate cancer.
PMID- 25120168
TI - Biochemical and molecular characterization of Avena indolines and their role in
kernel texture.
AB - Among cereals, Avena sativa is characterized by an extremely soft endosperm
texture, which leads to some negative agronomic and technological traits. On the
basis of the well-known softening effect of puroindolines in wheat kernel
texture, in this study, indolines and their encoding genes are investigated in
Avena species at different ploidy levels. Three novel 14 kDa proteins, showing a
central hydrophobic domain with four tryptophan residues and here named
vromindoline (VIN)-1,2 and 3, were identified. Each VIN protein in diploid oat
species was found to be synthesized by a single Vin gene whereas, in hexaploid A.
sativa, three Vin-1, three Vin-2 and two Vin-3 genes coding for VIN-1, VIN-2 and
VIN-3, respectively, were described and assigned to the A, C or D genomes based
on similarity to their counterparts in diploid species. Expression of oat
vromindoline transgenes in the extra-hard durum wheat led to accumulation of
vromindolines in the endosperm and caused an approximate 50 % reduction of grain
hardness, suggesting a central role for vromindolines in causing the extra-soft
texture of oat grain. Further, hexaploid oats showed three orthologous genes
coding for avenoindolines A and B, with five or three tryptophan residues,
respectively, but very low amounts of avenoindolines were found in mature
kernels. The present results identify a novel protein family affecting cereal
kernel texture and would further elucidate the phylogenetic evolution of Avena
genus.
PMID- 25120169
TI - Genome-wide identification of citrus ATP-citrate lyase genes and their transcript
analysis in fruits reveals their possible role in citrate utilization.
AB - ATP-citrate lyase (ACL, EC4.1.3.8) catalyzes citrate to oxaloacetate and acetyl
CoA in the cell cytosol, and has important roles in normal plant growth and in
the biosynthesis of some secondary metabolites. We identified three ACL genes,
CitACLalpha1, CitACLalpha2, and CitACLbeta1, in the citrus genome database. Both
CitACLalpha1 and CitACLalpha2 encode putative ACL alpha subunits with 82.5 %
amino acid identity, whereas CitACLbeta1 encodes a putative ACL beta subunit.
Gene structure analysis showed that CitACLalpha1 and CitACLalpha2 had 12 exons
and 11 introns, and CitACLbeta1 had 16 exons and 15 introns. CitACLalpha1 and
CitACLbeta1 were predominantly expressed in flower, and CitACLalpha2 was
predominantly expressed in stem and fibrous roots. As fruits ripen, the
transcript levels of CitACLalpha1, CitACLbeta1, and/or CitACLalpha2 in cultivars
'Niuher' and 'Owari' increased, accompanied by significant decreases in citrate
content, while their transcript levels decreased significantly in 'Egan No. 1'
and 'Iyokan', although citrate content also decreased. In 'HB pummelo', in which
acid content increased as fruit ripened, and in acid-free pummelo, transcript
levels of CitACLalpha2, CitACLbeta1, and/or CitACLalpha1 increased. Moreover,
mild drought stress and ABA treatment significantly increased citrate contents in
fruits. Transcript levels of the three genes were significantly reduced by mild
drought stress, and the transcript level of only CitACLbeta1 was significantly
reduced by ABA treatment. Taken together, these data indicate that the effects of
ACL on citrate use during fruit ripening depends on the cultivar, and the
reduction in ACL gene expression may be attributed to citrate increases under
mild drought stress or ABA treatment.
PMID- 25120171
TI - The clock is ticking: the sound of a ticking clock speeds up women's attitudes on
reproductive timing.
AB - The "biological clock" serves as a powerful metaphor that reflects the
constraints posed by female reproductive biology. The biological clock refers to
the progression of time from puberty to menopause, marking the period during
which women can conceive children. Findings from two experiments suggest that
priming the passage of time through the sound of a ticking clock influenced
various aspects of women's (but not men's) reproductive timing. Moreover,
consistent with recent research from the domain of life history theory, those
effects depended on women's childhood socioeconomic status (SES). The subtle
sound of a ticking clock led low (but not high) SES women to reduce the age at
which they sought to get married and have their first child (Study 1), as well as
the priority they placed on the social status and long-term earning potential of
potential romantic partners (Study 2). Findings suggest that early developmental
sensitization processes can interact with subtle environmental stimuli to affect
reproductive timing during adulthood.
PMID- 25120170
TI - Faculty survey to assess research literacy and evidence-informed practice
interest and support at Pacific College of Oriental Medicine.
AB - CONTEXT: Educating healthcare practitioners to understand, critically evaluate,
and apply evidence to the clinical practice of complementary and alternative
medicine has been an important initiative for the National Institutes of Health
National Center for Complementary and Alternative Medicine. OBJECTIVE: To
determine the self-assessed research skills and interest of faculty at Pacific
College of Oriental Medicine (New York campus) and their likely support of, and
participatory interest in, an evidence-based medicine (EBM) training program.
DESIGN: The survey was administered in Survey Monkey. All questions were close
ended with 5-point Likert answers, except for one open-ended question at the end
of the survey. SETTING: One of three campuses of Pacific College of Oriental
Medicine (PCOM), the largest Chinese medicine college in the United States.
PARTICIPANTS: 102 faculty employed at PCOM. RESULTS: The response rate was 88.7%.
Responses illustrated a generally high degree of interest and support for
research, EBM, and institutional participation in research activities. Faculty
who responded to the open-ended question (19.6% of respondents) expressed
concerns about the relevance of research to Chinese medicine and the possibility
of co-option by biomedicine. CONCLUSIONS: While faculty were overall supportive
and interested in research and EBM, the results are consistent with the
hypothesis that success of EBM training programs could be enhanced by soliciting
and addressing faculty concerns and by being inclusive of approaches that honor
the traditions of Chinese medicine and its own forms of clinical evidence.
PMID- 25120173
TI - Size, dimensionality, and strong electron correlation in nanoscience.
AB - In electronic structure theory, electron-electron repulsion is normally
considered only in an average (or mean field) sense, for example, in a single
Hartree-Fock determinant. This is the simple molecular orbital model, which is
often a good approximation for molecules. In infinite systems, this averaging
treatment leads to delocalized electronic bands, an excellent description of bulk
3D sp(3) semiconductors. However, in reality electrons try to instantaneously
avoid each other; their relative motion is correlated. Strong electron-electron
repulsion and correlation create new collective states and cause new femtosecond
kinetic processes. This is especially true in 1D and 2D systems. The quantum size
effect, a single electron property, is widely known: the band gap increases with
decreasing size. This Account focuses on the experimental consequences of strong
correlation. We first describe pi-pi* excited states in carbon nanotubes (CNTs).
To obtain the spectra of individual CNTs, we developed a white-light, right-angle
resonant Rayleigh scattering method. Discrete exciton transitions dominate the
optical absorption spectra of both semiconducting and metallic tubes. Excitons
are bound neutral excited states in which the electron and hole tightly orbit
each other due to their mutual Coulomb attraction. We then describe more
generally the independent roles of size and dimensionality in nanoelectronic
structure, using additional examples from graphene, trans-polyacetylene chains,
transition metal dichalcogenides, organic/inorganic Pb iodide perovskites,
quantum dots, and pentacene van der Waals crystals. In 1D and 2D chemical
systems, the electronic band structure diagram can be a poor predictor of
properties if explicit correlation is not considered. One- and two-dimensional
systems show quantum confinement and especially strong correlation as compared
with their 3D parent systems. The Coulomb interaction is enhanced because the
electrons are on the surface. One- and two-dimensional systems can exhibit
essentially molecular properties even though they are infinite in size. Zero
dimensional Qdots show quantum confinement and modest electron correlation.
Correlation is weak in 3D bulk semiconductors. Strongly correlated electronic
states can behave as if they have fractional charge and effectively separate the
spin and charge of the electron. This is apparent in the "soliton" state of
polyacetylene, the fractional charge quantum Hall state of graphene, and the
Luttinger electrical conductivity of metallic CNTs.
PMID- 25120172
TI - Short sleep duration reduces the risk of nonalcoholic fatty liver disease onset
in men: a community-based longitudinal cohort study.
AB - BACKGROUND: Epidemiologic studies show an association between short sleep
duration and the presence of nonalcoholic fatty liver disease (NAFLD). This study
examined the association between short sleep duration and the onset of NAFLD.
METHODS: This community-based, retrospective, longitudinal cohort study included
6,370 Japanese subjects who had undergone annual health check-ups more than twice
at a single center between April 2003 and March 2010. After excluding 3,941
subjects, the records of 2,429 Japanese subjects were reviewed. RESULTS: Two
groups comprised the study cohort: those with short (<= 6 h) sleep durations (n =
1,543) and those with moderate (7-8 h) sleep durations (n = 886). During the
observation period, 296 subjects developed NAFLD. Multivariate analysis
identified an association between short sleep duration and the reduced onset of
NAFLD in men (odds ratio: 0.551, 95% confidence interval 0.365-0.832, p = 0.005).
There was no association between short sleep duration and NAFLD onset in women.
The prevalence of NAFLD onset in men increased significantly as sleep duration
increased, as follows: 12.5, 18.4, and 27.4% among subjects who had sleep
durations of <= 4, 5-6, and 7-8 h, respectively (p = 0.02). CONCLUSIONS: This
study demonstrates an association between sleep duration and NAFLD onset. Short
sleep duration reduced the risk of NAFLD onset in men. Correct recognition is
important to prevent disease progression and further complications.
PMID- 25120174
TI - Incremental predictive value of natriuretic peptides for prognosis in the chronic
stable heart failure population: a systematic review.
AB - The aim of this study was to determine whether measurement of natriuretic
peptides independently adds incremental predictive value for mortality and
morbidity in patients with chronic stable heart failure (CSHF). We electronically
searched Medline(r), EmbaseTM, AMED, Cochrane Central Register of Controlled
Trials, Cochrane Database of Systematic Reviews, and CINAHL from 1989 to June
2012. We also searched reference lists of included articles, systematic reviews,
and the gray literature. Studies were screened for eligibility criteria and
assessed for methodological quality. Data were extracted on study design,
population demographics, assay cutpoints, prognostic risk prediction model
covariates, statistical methods, outcomes, and results. One hundred and eighty
three studies were identified as prognostic in the systematic review. From these,
15 studies (all NT-proBNP) considered incremental predictive value in CSHF
subjects. Follow-up varied from 12 to 37 months. All studies presented at least
one estimate of incremental predictive value of NT-proBNP relative to the base
prognostic model. Using discrimination or likelihood statistics, these studies
consistently showed that NT-proBNP increased model performance. Three studies
used re-classification and model validation computations to establish incremental
predictive value; these studies showed less consistency with respect to added
value. Although there were differences in the base risk prediction models, assay
cutpoints, and lengths of follow-up, there was consistency in NT-proBNP adding
incremental predictive value for prognostic models in chronic stable CSHF
patients. The limitations in the literature suggest that studies designed to
evaluate prognostic models should be undertaken to evaluate the incremental value
of natriuretic peptide as a predictor of mortality and morbidity in CSHF.
PMID- 25120175
TI - Quantitative short-wave infrared multispectral imaging of in vivo tissue optical
properties.
AB - Extending the wavelength range of spatial frequency domain imaging (SFDI) into
the short-wave infrared (SWIR) has the potential to provide enhanced sensitivity
to chromophores such as water and lipids that have prominent absorption features
in the SWIR region. Here, we present, for the first time, a method combining SFDI
with unstructured (zero spatial frequency) illumination to extract tissue
absorption and scattering properties over a wavelength range (850 to 1800 nm)
largely unexplored by previous tissue optics techniques. To obtain images over
this wavelength range, we employ a SWIR camera in conjunction with an SFDI
system. We use SFDI to obtain in vivo tissue reduced scattering coefficients at
the wavelengths from 850 to 1050 nm, and then use unstructured wide-field
illumination and an extrapolated power-law fit to this scattering spectrum to
extract the absorption spectrum from 850 to 1800 nm. Our proof-of-principle
experiment in a rat burn model illustrates that the combination of multispectral
SWIR imaging, SFDI, and unstructured illumination can characterize in vivo
changes in skin optical properties over a greatly expanded wavelength range. In
the rat burn experiment, these changes (relative to normal, unburned skin)
included increased absorption and increased scattering amplitude and slope,
consistent with changes that we previously reported in the near-infrared using
SFDI.
PMID- 25120176
TI - Conservative management of vestibular schwannomas of 15 to 31 mm intracranial
diameter.
AB - OBJECTIVE: To study the natural course of vestibular schwannomas 15 to 31 mm in
diameter. METHODS: A retrospective study of 45 patients conservatively managed
with interval scanning was performed. Outcome measures were: changes in tumour
size, clinical features and hearing. A tumour was considered to be growing if it
increased in size by more than 2 mm. RESULTS: Initial tumour sizes ranged from 15
to 31 mm, with a mean (+/- standard deviation) diameter of 20.1 +/- 4.3 mm. The
duration of follow up ranged from 6 months to 14 years (median, 3 years). Tumours
grew in 11 cases (24.4 per cent), remained stable in 30 cases (66.7 per cent) and
regressed in 4 cases (8.9 per cent). The overall mean tumour growth rate was 0.9
+/- 2.2 mm per year; in growing tumours, it was 3.6 +/- 2.9 mm per year.
CONCLUSION: Outcomes were similar to those reported for smaller tumours. These
findings suggest that patients with medium or moderately large tumours can be
safely offered an initial period of conservative management before intervention
is considered.
PMID- 25120177
TI - Personalizing energy expenditure estimation using physiological signals
normalization during activities of daily living.
AB - In this paper we propose a generic approach to reduce inter-individual
variability of different physiological signals (HR, GSR and respiration) by
automatically estimating normalization parameters (e.g. baseline and range). The
proposed normalization procedure does not require a dedicated personal
calibration during system setup. On the other hand, normalization parameters are
estimated at system runtime from sedentary and low intensity activities of daily
living (ADLs), such as lying and walking. When combined with activity-specific
energy expenditure (EE) models, our normalization procedure improved EE
estimation by 15 to 33% in a study group of 18 participants, compared to state of
the art activity-specific EE models combining accelerometer and non-normalized
physiological signals.
PMID- 25120178
TI - Magnitude of perceived depth of multiple stereo transparent surfaces.
AB - According to the geometric relational expression of binocular stereopsis, for a
given viewing distance the magnitude of the perceived depth of objects would be
the same, as long as the disparity magnitudes were the same. However, we found
that this is not necessarily the case for random-dot stereograms that depict
parallel, overlapping, transparent stereoscopic surfaces (POTS). The data from
five experiments indicated that (1) the magnitude of perceived depth between the
two outer surfaces of a three- or a four-POTS configuration can be smaller than
that for an identical pair of stereo surfaces of a two-POTS configuration for the
range of disparities that we used (5.2-19.4 arcmin); (2) this phenomenon can be
observed irrespective of the total dot density of a POTS configuration, at least
for the range that we used (1.1-3.3 dots/deg(2)); and (3) the magnitude of
perceived depth between the two outer surfaces of a POTS configuration can be
reduced as the total number of stereo surfaces is increased, up to four surfaces.
We explained these results in terms of a higher-order process or processes, with
an output representing perceived depth magnitude, which is weakened when the
number of its surfaces is increased.
PMID- 25120179
TI - The projected hand illusion: component structure in a community sample and
association with demographics, cognition, and psychotic-like experiences.
AB - The projected hand illusion (PHI) is a variant of the rubber hand illusion (RHI),
and both are commonly used to study mechanisms of self-perception. A
questionnaire was developed by Longo et al. (2008) to measure qualitative changes
in the RHI. Such psychometric analyses have not yet been conducted on the
questionnaire for the PHI. The present study is an attempt to validate minor
modifications of the questionnaire of Longo et al. to assess the PHI in a
community sample (n = 48) and to determine the association with selected
demographic (age, sex, years of education), cognitive (Digit Span), and clinical
(psychotic-like experiences) variables. Principal components analysis on the
questionnaire data extracted four components: Embodiment of "Other" Hand,
Disembodiment of Own Hand, Deafference, and Agency-in both synchronous and
asynchronous PHI conditions. Questions assessing "Embodiment" and "Agency" loaded
onto orthogonal components. Greater illusion ratings were positively associated
with being female, being younger, and having higher scores on psychotic-like
experiences. There was no association with cognitive performance. Overall, this
study confirmed that self-perception as measured with PHI is a multicomponent
construct, similar in many respects to the RHI. The main difference lies in the
separation of Embodiment and Agency into separate constructs, and this likely
reflects the fact that the "live" image of the PHI presents a more realistic
picture of the hand and of the stroking movements of the experimenter compared
with the RHI.
PMID- 25120180
TI - Large-scale analysis of posttranslational modifications in the hippocampus of
patients with Alzheimer's disease using pI shift and label-free quantification
without enrichment.
AB - Posttranslational modifications modulate protein function in cells. Global
analysis of multiple posttranslational modifications can provide insight into
physiology and disease, but presents formidable challenges. In the present study,
we used a technique that does not require target enrichment to analyze
alterations in the phosphorylation and ubiquitination of proteins from patients
with Alzheimer's disease (AD). Guided by our previous findings, we applied three
strategies to further our understanding of the dysregulation of
posttranslationally modified proteins. We first identified phosphorylation sites
by determining peptide pI shifts using OFFGEL. Second, using tandem mass
spectrometry, we determined the ubiquitination status of the proteins using an
assay for a trypsin digestion remnant of ubiquitination (Gly-Gly). Third, for
large-scale discovery, we quantified the global differences in protein
expression. Of the proteins expressed in AD tissue at levels of 2.0 or greater
compared with controls, 60 were phosphorylated and 56 were ubiquitinated. Of the
proteins expressed at levels of 0.5 or lower compared with controls, 81 were
phosphorylated and 56 were ubiquitinated. Approximately 98 % of the
phosphopeptides exhibited a pI shift. We identified 112 new phosphorylation sites
(51.38 %), and 92 new ubiquitination sites (96.84 %). Taken together, our
findings suggest that analysis of the alterations in posttranslationally modified
proteins may contribute to understanding the pathogenesis of AD and other
diseases.
PMID- 25120181
TI - Characterization and analysis of structural isomers of dimethyl methoxypyrazines
in cork stoppers and ladybugs (Harmonia axyridis and Coccinella septempunctata).
AB - The three constitutional isomers of dimethyl-substituted methoxypyrazines: 3,5
dimethyl-2-methoxypyrazine 1; 2,5-dimethyl-3-methoxypyrazine 2; and 2,3-dimethyl
5-methoxypyrazine 3 are potent flavor compounds with similar mass spectrometric,
gas chromatographic, and nuclear magnetic resonance spectroscopic behavior.
Therefore, unambiguous analytical determination is critical, particularly in
complex matrices. The unequivocal identification of 1-3 could be achieved by homo
and heteronuclear NMR correlation experiments. The observed mass fragmentation
for 1-3 is proposed and discussed, benefitting from synthesized partially
deuterated 1 and 2. On common polar and apolar stationary phases used in gas
chromatography (GC) 1 and 2 show similar behavior whereas 3 can be separated. In
our focus on off-flavor analysis with respect to wine aroma, 1 has been described
as a "moldy" off-flavor compound in cork and 2 as a constituent in Harmonia
axyridis contributing to the so-called "ladybug taint," whereas 3 has not yet
been described as a constituent of wine aroma. A successful separation of 1 and 2
could be achieved on octakis-(2,3-di-O-pentyl-6-O-methyl)-gamma-cyclodextrin as
stationary phase in GC. Applying heart-cut multidimensional GC analysis with
tandem mass spectrometric detection we could confirm the presence of 1 as a
"moldy" off-flavor compound in cork. However, in the case of Harmonia axyridis, a
previous identification of 2 has to be reconsidered. In our experiments we
identified the constitutional isomer 1, which was also found in Coccinella
septempunctata, another species discussed with respect to the "ladybug taint."
The analysis of such structurally related compounds is a demonstrative example
for the importance of a chromatographic separation, as mass spectrometric data by
itself could not guarantee the unequivocal identification.
PMID- 25120182
TI - A wide range optical pH sensor for living cells using Au@Ag nanoparticles
functionalized carbon nanotubes based on SERS signals.
AB - p-Aminothiophenol (pATP) functionalized multi-walled carbon nanotubes (MWCNTs)
have been demonstrated as an efficient pH sensor for living cells. The proposed
sensor employs gold/silver core-shell nanoparticles (Au@Ag NPs) functionalized
MWCNTs hybrid structure as the surface-enhanced Raman scattering (SERS) substrate
and pATP molecules as the SERS reporters, which possess a pH-dependent SERS
performance. By using MWCNTs as the substrate to be in a state of aggregation,
the pH sensing range could be extended to pH 3.0~14.0, which is much wider than
that using unaggregated Au@Ag NPs without MWCNTs. Furthermore, the pH-sensitive
performance was well retained in living cells with a low cytotoxicity. The
developed SERS-active MWCNTs-based nanocomposite is expected to be an efficient
intracellular pH sensor for bio-applications.
PMID- 25120183
TI - Relating surface-enhanced Raman scattering signals of cells to gold nanoparticle
aggregation as determined by LA-ICP-MS micromapping.
AB - The cellular response to nanoparticle exposure is essential in various contexts,
especially in nanotoxicity and nanomedicine. Here, 14-nm gold nanoparticles in
3T3 fibroblast cells are investigated in a series of pulse-chase experiments with
a 30-min incubation pulse and chase times ranging from 15 min to 48 h. The gold
nanoparticles and their aggregates are quantified inside the cellular
ultrastructure by laser ablation inductively coupled plasma mass spectrometry
micromapping and evaluated regarding the surface-enhanced Raman scattering (SERS)
signals. In this way, both information about their localization at the micrometre
scale and their molecular nanoenvironment, respectively, is obtained and can be
related. Thus, the nanoparticle pathway from endocytotic uptake, intracellular
processing, to cell division can be followed. It is shown that the ability of the
intracellular nanoparticles and their accumulations and aggregates to support
high SERS signals is neither directly related to nanoparticle amount nor to high
local nanoparticle densities. The SERS data indicate that aggregate geometry and
interparticle distances in the cell must change in the course of endosomal
maturation and play a critical role for a specific gold nanoparticle type in
order to act as efficient SERS nanoprobe. This finding is supported by TEM
images, showing only a minor portion of aggregates that present small
interparticle spacing. The SERS spectra obtained after different chase times show
a changing composition and/or structure of the biomolecule corona of the gold
nanoparticles as a consequence of endosomal processing.
PMID- 25120185
TI - Biotransformation and detectability of the designer drug 2,5-dimethoxy-4
propylphenethylamine (2C-P) studied in urine by GC-MS, LC-MS(n), and LC-high
resolution-MS(n).
AB - 2,5-Dimethoxy-4-propylphenethylamine (2C-P) is a hallucinogenic designer drug of
the phenethylamine class, the so-called 2Cs, named according to the ethyl spacer
between the nitrogen and the aromatic ring. The aims of the present work were to
identify the phases I and II metabolites of 2C-P. In addition, the detectability
of 2C-P and its metabolites in urine as proof of an intake in clinical or
forensic cases was tested. According to the identified metabolites, the following
pathways were proposed: N-acetylation; deamination followed by reduction to the
corresponding alcohol and oxidation to carbonic acid; mono- and bis-hydroxylation
at different positions; mono- and bis-O-demethylation, followed by
glucuronidation, sulfation, or both; and combination of these steps. Proof of an
intake of a common user's dose of 2C-P was possible by both standard urine
screening approaches, the GC-MS as well as the LC-MS(n) approach.
PMID- 25120184
TI - Emerging trends in precision fabrication of microapertures to support suspended
lipid membranes for sensors, sequencing, and beyond.
AB - Suspended lipid membranes, also called black lipid membranes (BLMs), are an
important model system that approximates the lipid bilayer environment of cell
membranes. Increasingly, BLMs are utilized in sensing strategies that harness
high sensitivity measurements of ion flux across the membrane, typically
facilitated by ion channel proteins. BLMs are suspended across microapertures
that connect two otherwise isolated fluidic compartments, and the precision
fabrication of such microapertures can contribute to the stability and
performance of the resulting BLM. Here, we highlight two emerging trends in the
precision fabrication of microapertures for BLM formation: microfabrication in
silicon-based thin film substrates, and microfabrication in the negative
photoresist material SU-8. Four unique fabrication strategies are outlined, and
we project the impact that these microfabrication strategies will have for BLM
integrated bioanalytical technologies.
PMID- 25120186
TI - Reproducibility of retention time and peak area in comprehensive two-dimensional
liquid chromatography.
AB - Comprehensive two-dimensional liquid chromatography is used to separate anionic,
nonionic, and amphoteric surfactants by substance class, alkyl chain
distribution, and degree of ethoxylation. A nearly orthogonal system with a
hydrophilic interaction chromatography (HILIC) phase in the first and a reversed
phase material in the second dimension is applied to generate a separation with
maximum peak capacity. The potential of the developed method is demonstrated by
the reproducibility of retention time and peak area, which shows standard
deviations less than 5 % and the analysis of real samples. An external
calibration and the standard addition method were applied to determine unknown
concentrations for the alkyl chain homologues of a betaine and for one ethoxylate
(EO) homologue of a fatty alcohol ethoxylate in a sample mixture.
PMID- 25120187
TI - Investigating the contribution of the active site environment to the slow
reaction of hypoxia-inducible factor prolyl hydroxylase domain 2 with oxygen.
AB - The prolyl hydroxylase domain proteins (PHDs) catalyse the post-translational
hydroxylation of the hypoxia-inducible factor (HIF), a modification that
regulates the hypoxic response in humans. The PHDs are Fe(II)/2-oxoglutarate
(2OG) oxygenases; their catalysis is proposed to provide a link between cellular
HIF levels and changes in O2 availability. Transient kinetic studies have shown
that purified PHD2 reacts slowly with O2 compared with some other studied 2OG
oxygenases, a property which may be related to its hypoxia-sensing role. PHD2
forms a stable complex with Fe(II) and 2OG; crystallographic and kinetic analyses
indicate that an Fe(II)-co-ordinated water molecule, which must be displaced
before O2 binding, is relatively stable in the active site of PHD2. We used
active site substitutions to investigate whether these properties are related to
the slow reaction of PHD2 with O2. While disruption of 2OG binding in a R383K
variant did not accelerate O2 activation, we found that substitution of the
Fe(II)-binding aspartate for a glutamate residue (D315E) manifested significantly
reduced Fe(II) binding, yet maintained catalytic activity with a 5-fold faster
reaction with O2. The results inform on how the precise active site environment
of oxygenases can affect rates of O2 activation and provide insights into
limiting steps in PHD catalysis.
PMID- 25120188
TI - Copeptin is not a useful biomarker for small-for-gestational-age: a case control
study.
AB - OBJECTIVE: To investigate copeptin as a biomarker for small-for-gestational-age.
METHODS: We conducted a nested case-control study on maternal copeptin levels
measured in gestational week 12 and 19 and risk of small-for-gestational age.
Cases were defined as pregnant women who delivered a small-for-gestational-age
infant. Small-for-gestational age was defined as a birth weight - 22% or less
than expected according to gestational age (n = 39). Controls were pregnant women
who delivered a normal-weight infant (n = 119). The copeptin ultrasensitive
Kryptor kit (BRAHMS) was used to determine copeptin in maternal serum. We
established reference ranges for copeptin by 95% prediction intervals with 90%
confidence intervals. Paired and unpaired t-tests were performed to test the null
hypothesis of no difference in copeptin levels within and between the groups.
RESULTS: The reference intervals for copeptin in normal pregnancies were 1.24
5.51 pmol/L (90% confidence intervals on upper and lower limit were 1.13-1.37 and
5.00-6.08 pmol/L) at gestational week 12, and 1.30-5.09 pmol/L (90% confidence
intervals were 1.19-1.42 and 4.65-5.57 pmol/L) at gestational week 19. Copeptin
levels decreased from week 12-19 in cases (p = 0.02), whereas no change was
observed in controls (p = 0.61). We found no difference in copeptin levels in
cases compared to controls in gestational week 12 (p = 0.10) and week 19 (p =
0.81). CONCLUSION: The present study could not demonstrate copeptin as a novel
biomarker for small-for-gestational-age.
PMID- 25120189
TI - Gate-opening gas adsorption and host-guest interacting gas trapping behavior of
porous coordination polymers under applied AC electric fields.
AB - The gate-opening adsorption behavior of the one-dimensional chain compound [Ru2(4
Cl-2-OMePhCO2)4(phz)] (1; 4-Cl-2-OMePhCO2(-) = 4-chloro-o-anisate; phz =
phenazine) for various gases (O2, NO, and CO2) was electronically monitored in
situ by applying ac electric fields to pelletized samples attached to a cryostat,
which was used to accurately control the temperature and gas pressure. The gate
opening and -closing transitions induced by gas adsorption/desorption,
respectively, were accurately monitored by a sudden change in the real part of
permittivity (epsilon'). The transition temperature (TGO) was also found to be
dependent on the applied temperature and gas pressure according to the Clausius
Clapeyron equation. This behavior was also observed in the isostructural compound
[Rh2(4-Cl-2-OMePhCO2)4(phz)] (2), which exhibited similar gate-opening adsorption
properties, but was not detected in the nonporous gate-inactive compound [Ru2(o
OMePhCO2)4(phz)] (3). Furthermore, the imaginary part of permittivity (epsilon")
effectively captured the electronic perturbations of the samples induced by the
introduced guest molecules. Only the introduction of NO resulted in the increase
of the sample's electronic conductivity for 1 and 3, but not for 2. This behavior
indicates that electronic host-guest interactions were present, albeit very weak,
at the surface of sample 1 and 3, i.e., through grain boundaries of the sample,
which resulted in perturbation of the conduction band of this material's
framework. This technique involving the in situ application of ac electric fields
is useful not only for rapidly monitoring gas sorption responses accompanied by
gate-opening/-closing structural transitions but also potentially for the
development of molecular framework materials as chemically driven electronic
devices.
PMID- 25120190
TI - Telomerase inhibition abolishes the tumorigenicity of pediatric ependymoma tumor
initiating cells.
AB - Pediatric ependymomas are highly recurrent tumors resistant to conventional
chemotherapy. Telomerase, a ribonucleoprotein critical in permitting limitless
replication, has been found to be critically important for the maintenance of
tumor-initiating cells (TICs). These TICs are chemoresistant, repopulate the
tumor from which they are identified, and are drivers of recurrence in numerous
cancers. In this study, telomerase enzymatic activity was directly measured and
inhibited to assess the therapeutic potential of targeting telomerase. Telomerase
repeat amplification protocol (TRAP) (n = 36) and C-circle assay/telomere
FISH/ATRX staining (n = 76) were performed on primary ependymomas to determine
the prevalence and prognostic potential of telomerase activity or alternative
lengthening of telomeres (ALT) as telomere maintenance mechanisms, respectively.
Imetelstat, a phase 2 telomerase inhibitor, was used to elucidate the effect of
telomerase inhibition on proliferation and tumorigenicity in established cell
lines (BXD-1425EPN, R254), a primary TIC line (E520) and xenograft models of
pediatric ependymoma. Over 60 % of pediatric ependymomas were found to rely on
telomerase activity to maintain telomeres, while no ependymomas showed evidence
of ALT. Children with telomerase-active tumors had reduced 5-year progression
free survival (29 +/- 11 vs 64 +/- 18 %; p = 0.03) and overall survival (58 +/-
12 vs 83 +/- 15 %; p = 0.05) rates compared to those with tumors lacking
telomerase activity. Imetelstat inhibited proliferation and self-renewal by
shortening telomeres and inducing senescence in vitro. In vivo, Imetelstat
significantly reduced subcutaneous xenograft growth by 40 % (p = 0.03) and
completely abolished the tumorigenicity of pediatric ependymoma TICs in an
orthotopic xenograft model. Telomerase inhibition represents a promising
therapeutic approach for telomerase-active pediatric ependymomas found to
characterize high-risk ependymomas.
PMID- 25120192
TI - Anti-Abeta antibody target engagement: commentary regarding Watt et al. Acta
Neuropathol 127:803-810 (2014).
PMID- 25120191
TI - C9orf72 FTLD/ALS-associated Gly-Ala dipeptide repeat proteins cause neuronal
toxicity and Unc119 sequestration.
AB - Hexanucleotide repeat expansion in C9orf72 is the most common pathogenic mutation
in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar
degeneration (FTLD). Despite the lack of an ATG start codon, the repeat expansion
is translated in all reading frames into dipeptide repeat (DPR) proteins, which
form insoluble, ubiquitinated, p62-positive aggregates that are most abundant in
the cerebral cortex and cerebellum. To specifically analyze DPR toxicity and
aggregation, we expressed DPR proteins from synthetic genes containing a start
codon but lacking extensive GGGGCC repeats. Poly-Gly-Ala (GA) formed p62-positive
cytoplasmic aggregates, inhibited dendritic arborization and induced apoptosis in
primary neurons. Quantitative mass spectrometry analysis to identify poly-GA co
aggregating proteins revealed a significant enrichment of proteins of the
ubiquitin-proteasome system. Among the other interacting proteins, we identified
the transport factor Unc119, which has been previously linked to neuromuscular
and axonal function, as a poly-GA co-aggregating protein. Strikingly, the levels
of soluble Unc119 are strongly reduced upon poly-GA expression in neurons,
suggesting a loss of function mechanism. Similar to poly-GA expression, Unc119
knockdown inhibits dendritic branching and causes neurotoxicity. Unc119
overexpression partially rescues poly-GA toxicity suggesting that poly-GA
expression causes Unc119 loss of function. In C9orf72 patients, Unc119 is
detectable in 9.5 % of GA inclusions in the frontal cortex, but only in 1.6 % of
GA inclusions in the cerebellum, an area largely spared of neurodegeneration. A
fraction of neurons with Unc119 inclusions shows loss of cytosolic staining. Poly
GA-induced Unc119 loss of function may thereby contribute to selective
vulnerability of neurons with DPR protein inclusions in the pathogenesis of
C9orf72 FTLD/ALS.
PMID- 25120194
TI - Effective implementation of health information technologies in U.S. hospitals.
AB - OBJECTIVES: Two issues pertaining to the effective implementation of health
information technologies (HITs) in U.S. hospitals are examined. First, which
information technology (IT) system is better--a homegrown or an outsourced one?
In the second issue, the critical role of in-house IT expertise/capabilities in
the effective implementation of HITs is investigated. STUDY DESIGN/DATA
COLLECTION: The data on type of HIT system and IT expertise/capabilities were
collected from a national sample of senior executives of U.S. hospitals. The data
on quality of patient care were gathered from the Hospital Compare Web site.
FINDINGS: The quality of patient care was significantly higher in hospitals
deploying a homegrown HIT system than hospitals deploying an outsourced HIT
system. Furthermore, the professional competence and compelling vision of the
chief information officer was found to be a major driver of another key IT
capability of hospitals-professionalism of IT staff. The positive relationship of
professionalism of IT staff with quality of patient care was mediated by
proactive employee behavior. CONCLUSION: A homegrown HIT system achieves better
quality of patient care than an outsourced one. The chief information officer's
IT vision and the professional expertise and professionalism of IT staff are
important IT capabilities in U.S. hospitals.
PMID- 25120193
TI - Anti-Abeta antibody target engagement: a response to Siemers et al.
PMID- 25120195
TI - Cumulative impact of periodic top-down communications on infection prevention
practices and outcomes in two units.
AB - BACKGROUND: The problem of interest in this study is the challenge of consistent
implementation of evidence-based infection prevention practices at the unit
level, a challenge broadly characterized as "change implementation failure." The
theoretical literature suggests that periodic top-down communications promoting
tacit knowledge exchanges across professional subgroups may be effective for
enabling change in health care organizations. However, gaps remain in
understanding the mechanisms by which top-down communications enable practice
change at the unit level. Our study sought to both validate the theoretical
literature and address this gap. PURPOSE: Correspondingly, this study posed two
research questions. (1) What is the impact of periodic "top-down" communications
on practice change at the unit level? (2) What are the "unit-level" communication
dynamics enabling practice changes? Whereas this article focuses on addressing
the first question, the second question has been addressed in an earlier Health
Care Management Review article (Rangachari et al., 2013). METHODS: A prospective
study was conducted in two intensive care units at an academic health center.
Both units had low baseline adherence to central line bundle (CLB) and higher
than-expected catheter-related bloodstream infections (CRBSIs). Periodic top-down
communication interventions were conducted over 52 weeks to promote CLB adherence
in both units. Simultaneously, the study examined (a) unit-level communication
dynamics related to CLB through weekly "communication logs," completed by unit
physicians, nurses, and managers, and (b) unit outcomes, that is, CLB adherence
and CRBSI rates. FINDINGS: Both units showed increased adherence to CLB and
significant, sustained declines in CRBSIs. Results showed that the interventions
cumulatively had a significant negative (desired) impact on "catheter days," that
is, central catheter use. PRACTICE IMPLICATIONS: Results help validate the
theoretical literature and identify evidence-based management strategies for
practice change at the unit level. They suggest that periodic top-down
communications have the potential to modify interprofessional knowledge exchanges
and enable practice change at the unit level, leading to significantly improved
outcomes and reduced costs.
PMID- 25120196
TI - Within-subject comparison of word recognition and spiral ganglion cell count in
bilateral cochlear implant recipients.
AB - OBJECTIVES: Although published reports have not demonstrated a positive
correlation between the number of residual spiral ganglion cells (SGCs) and word
recognition scores in patients with unilateral multichannel cochlear implants,
this study was designed to retest this hypothesis in patients with bilateral
multichannel cochlear implants. MATERIALS AND METHODS: From a pool of 133
temporal bones, all subjects with bilateral multichannel cochlear implants who
were deafened bilaterally by the same etiology were studied. A total of 12
temporal bones from 6 subjects were identified and processed after death for
histology. The SGCs were counted using standard techniques. The differences
between left and right SGC counts as well as the differences in word recognition
scores were calculated for each subject. Correlation analysis was performed
between the differences of SGC counts and the differences of word recognition
scores. RESULTS: Differences in SGC counts were highly correlated with the
differences in word recognition scores (R = 0.934, p = 0.006). CONCLUSION: This
study suggests higher residual SGCs predicted better performance after
implantation in a given patient. The results also support attempts to identify
factors which may promote survival of SGCs.
PMID- 25120197
TI - Documentation and localization of force-mediated filamin A domain perturbations
in moving cells.
AB - Endogenously and externally generated mechanical forces influence diverse
cellular activities, a phenomenon defined as mechanotransduction. Deformation of
protein domains by application of stress, previously documented to alter
macromolecular interactions in vitro, could mediate these effects. We engineered
a photon-emitting system responsive to unfolding of two repeat domains of the
actin filament (F-actin) crosslinker protein filamin A (FLNA) that binds multiple
partners involved in cell signalling reactions and validated the system using F
actin networks subjected to myosin-based contraction. Expressed in cultured
cells, the sensor-containing FLNA construct reproducibly reported FLNA domain
unfolding strikingly localized to dynamic, actively protruding, leading cell
edges. The unfolding signal depends upon coherence of F-actin-FLNA networks and
is enhanced by stimulating cell contractility. The results establish protein
domain distortion as a bona fide mechanism for mechanotransduction in vivo.
PMID- 25120199
TI - The "tale" of poly(A) binding protein: the MLLE domain and PAM2-containing
proteins.
AB - The cytoplasmic poly(A) binding protein 1 (PABPC1) is an essential eukaryotic
translational initiation factor first described over 40 years ago. Most studies
of PABPC1 have focused on its N-terminal RRM domains, which bind the mRNA 3'
poly(A) tail and 5' translation complex eIF4F via eIF4G; however, the protein
also contains a C-terminal MLLE domain that binds a peptide motif, termed PAM2,
found in many proteins involved in translation regulation and mRNA metabolism.
Studies over the past decade have revealed additional functions of PAM2
containing proteins (PACs) in neurodegenerative diseases, circadian rhythms,
innate defense, and ubiquitin-mediated protein degradation. Here, we summarize
functional and structural studies of the MLLE/PAM2 interaction and discuss the
diverse roles of PACs.
PMID- 25120198
TI - Deficiency of MAPK-activated protein kinase 2 (MK2) prevents adverse remodelling
and promotes endothelial healing after arterial injury.
AB - Maladaptive remodelling of the arterial wall after mechanical injury (e. g.
angioplasty) is characterised by inflammation, neointima formation and media
hypertrophy, resulting in narrowing of the affected artery. Moreover, mechanical
injury of the arterial wall causes loss of the vessel protecting endothelial cell
monolayer. Mitogen-activated protein kinase (MAPK)-activated protein kinase 2
(MK2), a major downstream target of p38 MAPK, regulates inflammation, cell
migration and proliferation, essential processes for vascular remodelling and re
endothelialisation. Therefore, we investigated the role of MK2 in remodelling and
re-endothelialisation after arterial injury in genetically modified mice in vivo.
Hypercholesterolaemic low-density-lipoprotein-receptor-deficient mice (ldlr-/-)
were subjected to wire injury of the common carotid artery. MK2-deficiency (ldlr
/-/mk2-/-) nearly completely prevented neointima formation, media hypertrophy,
and lumen loss after injury. This was accompanied by reduced proliferation and
migration of MK2-deficient smooth muscle cells. In addition, MK2-deficiency
severely reduced monocyte adhesion to the arterial wall (day 3 after injury,
intravital microscopy), which may be attributed to reduced expression of the
chemokine ligands CCL2 and CCL5. In line, MK2-deficiency significantly reduced
the content of monocytes, neutrophiles and lymphocytes of the arterial wall (day
7 after injury, flow cytometry). In conclusion, in a model of endothelial injury
(electric injury), MK2-deficiency strongly increased proliferation of endothelial
cells and improved re-endothelialisation of the arterial wall after injury.
Deficiency of MK2 prevents adverse remodelling and promotes endothelial healing
of the arterial wall after injury, suggesting that MK2-inhibition is a very
attractive intervention to prevent restenosis after percutaneous therapeutic
angioplasty.
PMID- 25120201
TI - Wilson's disease presenting as rapid eye movement sleep behavior disorder: a
possible window to early treatment.
AB - OBJECTIVE: To describe characteristics of REM sleep behavior disorder in Wilson's
disease. METHOD: Questionnaire-based interviews (patients and relatives),
neurological examinations, two-week prospective dream-diary, video
polysomnography, transcranial sonography, MRI. RESULTS: Four Wilson's disease
cases with REM sleep behavior disorder were described; three had REM sleep
behavior disorder as initial symptom. All showed mesencephalic tegmental/tectal
sonographic hyperechogenicities and two presented ponto-mesencephalic tegmental
MRI hyperintensities. CONCLUSION: This first description of REM sleep behavior
disorder in Wilson's disease in literature documents REM sleep behavior disorder
as a possible presenting symptom of Wilson's disease and adds further evidence to
the parallelism of Parkinson's disease and Wilson's disease in phenotype and
brainstem topography, which ought to be further studied. REM sleep behavior
disorder has prognostic relevance for neurodegeneration in alpha
synucleinopathies. In Wilson's disease, usefulness of early diagnosis and
treatment are already well established. REM sleep behavior disorder in Wilson's
disease offers a possible theoretical model for potential early treatment in this
extrapyramidal and brainstem paradigm syndrome, previewing the possibility of
neuroprotective treatment for REM sleep behavior disorder in "pre-clinical"
Parkinson's disease.
PMID- 25120202
TI - Electroencephalographic and behavioral effects of intracerebroventricular or
intraperitoneal injections of toxic honey extract in adult Wistar rats and GAERS.
AB - Toxic honey, containing grayanotoxin, is obtained from nectar and polen of
rhododendron. Consumed in excess it produces seizures and convulsions. In order
to investigate whether the toxic honey extract can be used as a seizure model, we
examined the electroencephalographic (EEG) and motor effects of
intracerebroventricular (icv) or intraperitoneal (ip) injection of toxic honey
extract in Wistar rats or in genetic absence epilepsy rats from Strasbourg
(GAERS). Male Wistar rats or GAERS were stereotaxically implanted with bilateral
cortical recording electrodes in all ip groups and cannula in the icv groups.
Based on the previous study, an extract was obtained from the non-toxic and toxic
honey. After the injection of the non-toxic or toxic honey extract, seizure
stages and changes in EEG were evaluated from 9 am to noon. The icv
administration of toxic honey extract produced stage 4 seizures and bilateral
cortical spikes within 30-60 min and these effects disappeared after 120 min in
Wistar rats or GAERS. The mean of bilateral cortical spike acitivity in EEG of
Wistar rats was 804.2 +/- 261.0 s in the 3-h period. After the icv administration
of toxic honey extract to GAERS, the mean duration of spike-and-wave discharges
(SWDs) in GAERS significantly decreased during the first 60 min and then returned
to baseline level. Ip injection of toxic honey extract caused no seizure and no
change in EEG in either GAERS or Wistars. These results suggest that the icv
administration of toxic honey extract can be used as a seizure model.
PMID- 25120200
TI - Improving outcomes for youth with ADHD: a conceptual framework for combined
neurocognitive and skill-based treatment approaches.
AB - Attention-deficit/hyperactivity disorder (ADHD) is a prevalent and chronic mental
health condition that often results in substantial impairments throughout life.
Although evidence-based pharmacological and psychosocial treatments exist for
ADHD, effects of these treatments are acute, do not typically generalize into non
treated settings, rarely sustain over time, and insufficiently affect key areas
of functional impairment (i.e., family, social, and academic functioning) and
executive functioning. The limitations of current evidence-based treatments may
be due to the inability of these treatments to address underlying neurocognitive
deficits that are related to the symptoms of ADHD and associated areas of
functional impairment. Although efforts have been made to directly target the
underlying neurocognitive deficits of ADHD, extant neurocognitive interventions
have shown limited efficacy, possibly due to misspecification of training targets
and inadequate potency. We argue herein that despite these limitations, next
generation neurocognitive training programs that more precisely and potently
target neurocognitive deficits may lead to optimal outcomes when used in
combination with specific skill-based psychosocial treatments for ADHD. We
discuss the rationale for such a combined treatment approach, prominent examples
of this combined treatment approach for other mental health disorders, and
potential combined treatment approaches for pediatric ADHD. Finally, we conclude
with directions for future research necessary to develop a combined
neurocognitive + skill-based treatment for youth with ADHD.
PMID- 25120203
TI - Study of proximal femoral bone perfusion with 3D T1 dynamic contrast-enhanced
MRI: a feasibility study.
AB - OBJECTIVE: The objective of this study was to compare measurements of semi
quantitative and pharmacokinetic parameters in areas of red (RBM) and yellow bone
marrow (YBM) of the hip, using an in-house high-resolution DCE T1 sequence, and
to assess intra- and inter-observer reproducibility of these measurements.
METHODS: The right hips of 21 adult patients under 50 years of age were studied.
Spatial resolution was 1.8 * 1.8 * 1.8 mm(3), and temporal resolution was 13.5
seconds. Two musculoskeletal radiologists independently processed DCE images and
measured semi-quantitative and pharmacokinetic parameters in areas of YBM and
RBM. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated.
Intra- and inter-observer reproducibility was assessed. RESULTS: Area under the
curve (AUC) and initial slope (IS) were significantly greater for RBM than for
YBM (p < 0.05). K(trans) and kep were also significantly greater for RBM (p <
0.05). There was no significant difference in time to peak between the regions (p
< 0.05). SNR, CNR, and intra- and inter-observer reproducibility were all good.
CONCLUSIONS: DCE study of the whole hip is feasible with high spatial resolution
using a 3D T1 sequence. Measures were possible even in low vascularized areas of
the femoral head. K(trans), kep, AUC, and IS values were significantly different
between red and yellow marrow, whereas TTP values were not. KEY POINTS: High
spatial-resolution dynamic contrast-enhanced MRI of hip structures is feasible.
Intra- and inter-observer reproducibility is good. Red and yellow bone marrow
have different perfusion patterns.
PMID- 25120204
TI - Anatomic variants of the pancreatic duct and their clinical relevance: an MR
guided study in the general population.
AB - OBJECTIVES: To investigate the frequency of pancreatic duct (PD) variants and
their effect on pancreatic exocrine function in a population-based study using
non-invasive secretin-stimulated magnetic resonance cholangiopancreatography
(sMRCP). METHODS: Nine hundred and ninety-five volunteers, 457 women and 538 men,
aged 51.9 +/- 13.4 years, underwent navigator-triggered, T2-weighted, 3D turbo
spin echo MRCP on a 1.5 T system after 1 unit/kg secretin administration. Two
readers evaluated images for PD variants. Pancreatic exocrine function and
morphological signs of chronic pancreatitis such as abnormalities of the main PD,
side branch dilatation, and pancreatic cysts were evaluated and related to PD
variants using a Kruskal-Wallis test and post hoc analysis. RESULTS: Of all
sMRCP, 93.2% were of diagnostic quality. Interobserver reliability for detection
of PD variants was found to be kappa 0.752 (95 %CI, 0.733 - 0.771). Normal PD
variants were observed in 90.4% (n = 838/927). Variants of pancreas divisum was
identified in 9.6% (n = 89/927). Abnormalities of the main PD, side branch
dilatation, and pancreatic cysts were observed in 2.4%, 16.6%, and 27.7%,
respectively, and were not significantly different between pancreas divisum and
non-divisum group (P = 0.122; P = 0.152; P = 0.741). There was no association
between PD variants and pancreatic exocrine function (P = 0.367). CONCLUSION: PD
variants including pancreas divisum are not associated with morphological signs
of chronic pancreatitis or restriction of pancreatic exocrine function. KEY
POINTS: MRCP allows the evaluation of pancreatic duct variants and morphological
change. Pancreatic duct variants are not associated with morphological signs of
chronic pancreatitis. Pancreas divisum is not accompanied by restriction of
pancreatic exocrine function. Pancreatic duct variants including pancreas divisum
are limited in their clinical relevance.
PMID- 25120205
TI - Differentiation of focal nodular hyperplasia from hepatocellular adenomas with
low-mechanical-index contrast-enhanced sonography (CEUS): effect of size on
diagnostic confidence.
AB - PURPOSE: The purpose of this study was to assess the diagnostic performance of
contrast-enhanced sonography (CEUS) for the differentiation of focal nodular
hyperplasia (FNH) from hepatocellular adenoma (HCA) according to lesion size.
MATERIALS AND METHODS: Forty patients with a definite diagnosis of FNH or HCA who
underwent CEUS were included in this institutional review board (IRB)-approved
study. A total of 43 FNHs and 20 HCAs, including 15 inflammatory HCAs and five
unclassified HCAs, were analysed. Two radiologists reviewed the diagnostic CEUS
parameters separately and in consensus, including the presence or absence of
centrifugal filling and central vessels. The sensitivity (Se), specificity (Sp),
and inter-observer confidence (Kappa) of CEUS diagnostic parameters were
assessed. RESULTS: Inter-observer agreement of CEUS for FNH diagnosis was high
(kappa = 0.81) with an overall Se of 67.4% [29/43 (CI 95%: 51.4-80.1 %)] and an
Sp of 100% [20/20 (CI 95%: 81-100%)]. Significantly higher Se figures were found
for lesions <= 35 mm than for lesions > 35 mm [respectively, 93 % (28/30) (CI
95%: 77.6-99.2) vs. 7.7% (1/13) (CI 95%: 0.2-36%), p = 0.002] with unchanged
specificity. CONCLUSION: CEUS is highly specific for the diagnosis of FNH, with
very good inter-observer agreement, whatever the size, but its sensitivity is
significantly reduced in diagnosing lesions larger than 35 mm. KEY POINTS: * CEUS
is highly specific for the diagnosis of FNH, regardless of lesion size * CEUS
shows reduced sensitivity in diagnosing FNH lesions larger than 35 mm * The
filling patterns of hepatocellular adenomas are not affected by lesion size.
PMID- 25120208
TI - Synthesis and structures of tris(2-pyridyl)aluminate sandwich compounds [{RAl(2
py')2}2M] (py' = 2-pyridyl, M = Ca, Mn, Fe).
AB - Reactions of the lithium salts [{RAl(2-py')3Li.THF] [2-py' = 2-py (2-pyridyl), R
= (n)Bu (1), R = (sec)Bu (2); py' = 5-Me-2-py (5-methyl-2-pyridyl), R = Me (3); 6
Me-2-py (6-methyl-2-pyridyl), R = Et (4b)] with the corresponding metal(ii)
halides give the new heterobimetallic sandwich compounds [{RAl(2-py)3}2M] [R =
(n)Bu, M = Ca (5), Mn (6), Fe (7); R = (sec)Bu, M = Ca (8), Mn (9)], [{MeAl(5-Me
2-py)3}2Ca] (10) and [{EtAl(6-Me-2-py)3}2Ca] (11) and the co-complex [{EtAl(6-Me
2-py)3}Mn(MU-Cl)Li{(6-Me-2-py)3AlEt}] (12). While neither the bridgehead group
(R) nor remote ring Me-groups have any impact on metal coordination in 5-10, the
introduction of Me groups into the pyridyl substituent at the 6-position (i.e.,
adjacent to the donor pyridyl-N atoms) has a marked effect on the ability of the
ligands to form sandwich arrangements, as seen in the distorted structure of the
sandwich compound 11 and in the formation of the co-complex 12, consisting of a
two half-sandwich arrangement linked by a MU-Cl ion. The syntheses and solid
state structures of the new precursor 4b and the new compounds 5-12 are reported.
PMID- 25120206
TI - Correlations of (18)F-fluorothymidine uptake with pathological tumour size, Ki-67
and thymidine kinase 1 expressions in primary and metastatic lymph node
colorectal cancer foci.
AB - OBJECTIVE: To examine correlations of (18)F-fluorothymidine (FLT) uptake with
pathological tumour size and immunohistochemical Ki-67, and thymidine kinase 1
(TK-1) expressions in primary and metastatic node colorectal cancer foci.
METHODS: Thirty primary cancers (PCs) and 37 metastatic nodes (MNs) were
included. FLT uptake was assessed by visual scores (non-visible: 0-1 and visible:
2-4), standardized uptake value (SUV), and correlated with size, Ki-67, and TK-1.
SUV was measured in visible lesions. FLT heterogeneity was assessed by visual
scores (no heterogeneous uptake: 0 and heterogeneous uptake: 1-4). RESULTS: Forty
two lesions were visible. The visible group showed significantly higher values
than the non-visible group in size, Ki-67, and TK-1 (each p < 0.05). Size
correlated significantly with visual score (PC; rho = 0.74 and MN; rho = 0.63),
SUVmax (PC; rho = 0.49, and MN; rho = 0.76), and SUVmean (PC; rho = 0.40 and MN;
rho = 0.76) (each p < 0.05). Visual score correlated significantly with size (rho
= 0.86), Ki-67max (rho = 0.35), Ki-67mean (rho = 0.38), TK-1max (rho = 0.35) and
TK-1mean (rho = 0.25) (each p < 0.05). No significant correlations were found
between FLT uptake and Ki-67 or TK-1 in 42 visible lesions (each p > 0.05).
Heterogeneous FLT uptake was noted in 73 % (22/30) of PCs. CONCLUSION: FLT uptake
correlated with size. Heterogeneous FLT distribution in colorectal cancers may be
one of the causes of weak or lack of FLT uptake/Ki-67 or TK-1 correlation. KEY
POINTS: FLT uptake correlated well with tumour size in colorectal cancer. Weak or
lack of FLT uptake/Ki-67 and TK-1 correlations were observed. Immunohistochemical
Ki-67 and TK-1 expressions are not always correlated with FLT uptake.
PMID- 25120207
TI - Non-invasive biomechanical characterization of intervertebral discs by shear wave
ultrasound elastography: a feasibility study.
AB - OBJECTIVES: Although magnetic resonance is widely spread to assess qualitatively
disc morphology, a simple method to determine reliably intervertebral disc status
is still lacking. Shear wave elastography is a novel technique that allows
quantitative evaluation of soft-tissues' mechanical properties. The aim of this
study was to assess preliminary the feasibility and reliability of mechanical
characterization of cervical intervertebral discs by elastography and to provide
first reference values for asymptomatic subjects. METHODS: Elastographic
measurements were performed to determine shear wave speed (SWS) in C6-C7 or C7-T1
disc of 47 subjects; repeatability and inter-operator reproducibility were
assessed. RESULTS: Global average shear wave speed (SWS) was 3.0 +/- 0.4 m/s;
measurement repeatability and inter-user reproducibility were 7 and 10%,
respectively. SWS was correlated with both subject's age (p = 1.3 * 10(-5)) and
body mass index (p = 0.008). CONCLUSIONS: Shear wave elastography in
intervertebral discs proved reliable and allowed stratification of subjects
according to age and BMI. Applications could be relevant, for instance, in early
detection of disc degeneration or in follow-up after trauma; these results open
the way to larger cohort studies to define the place of this technique in routine
intervertebral disc assessment. KEY POINTS: A simple method to obtain objectively
intervertebral disc status is still lacking. Shear wave elastography was applied
in vivo to assess intervertebral discs. Elastography showed promising results in
biomechanical disc evaluation. Elastography could be relevant in clinical routine
for intervertebral disc assessment.
PMID- 25120209
TI - Targeting the PI3K/Akt pathway in prostate cancer: challenges and opportunities
(review).
AB - The PI3K/Akt pathway is an actively pursued therapeutic target in oncology. In
prostate cancer, the activation of this pathway appears to be characteristic of
many aggressive prostate cancers. Further, activation of the PI3K/Akt pathway is
more frequently observed as prostate cancer progresses toward a resistant,
metastatic disease. Signalling from this pathway activates numerous survival,
growth, metabolic and metastatic functions characteristic of aggressive cancer.
Biomarkers of this pathway have correlated activation of this pathway to high
grade disease and higher risk of disease progression. Therefore there is
significant interest in developing effective strategies to target this pathway in
prostate cancer. In this review, we discuss the pre-clinical and clinical data
relevant to targeting of the PI3K/Akt pathway in prostate cancer. In particular,
we review the rationale and relevance of co-targeting approaches against the
PI3K/Akt pathway. It is anticipated that through an improved understanding of the
biology of the PI3K/Akt pathway in prostate cancer, relevant biomarkers and
rationale combination therapies will optimize targeting of this pathway to
improve outcomes among patients with aggressive prostate cancer.
PMID- 25120210
TI - Mapping central alpha-helix linker mediated conformational transition pathway of
calmodulin via simple computational approach.
AB - The effects of intrinsic structural flexibility of calmodulin protein on the
mechanism of its allosteric conformational transition are investigated in this
article. Using a novel in silico approach, the conformational transition pathways
of intact calmodulin as well as the isolated N- and C- terminal domains are
identified and energetically characterized. It is observed that the central alpha
helix linker amplifies the structural flexibility of intact Ca(2+)-free
calmodulin, which might facilitate the transition of the two domains. As a
result, the global conformational transition of Ca(2+)-free calmodulin is
initiated by the barrierless transition of two domains and proceeds through the
barrier associated unwinding and bending of the central alpha-helix linker. The
binding of Ca(2+) cations to calmodulin further increases the structural
flexibility of the C-terminal domain and results in a downhill transition pathway
of which all regions transit in a concerted manner. On the other hand, the
separation of the N- and C-terminal domains from calmodulin protein loses the
mediating function of central alpha-helix linker, leading to more difficult
conformational transitions of both domains. The present study provides novel
insights into the correlation of the integrity of protein, the structural
flexibility, and the mechanism of conformational transition of proteinlike
calmodulin.
PMID- 25120211
TI - Perioperative cardiovascular complications versus perioperative bleeding in
consecutive patients with known cardiac disease undergoing non-cardiac surgery.
Focus on antithrombotic medication. The PRAGUE-14 registry.
AB - BACKGROUND: Interruption of antithrombotic treatment before surgery may prevent
bleeding, but at the price of increasing cardiovascular complications. This
prospective study analysed the impact of antithrombotic therapy interruption on
outcomes in non-selected surgical patients with known cardiovascular disease
(CVD). METHODS: All 1200 consecutive patients (age 74.2 +/- 10.2 years)
undergoing major non-cardiac surgery (37.4 % acute, 61.4 % elective) during a
period of 2.5 years while having at least one CVD were enrolled. Details on
medication, bleeding, cardiovascular complications and cause of death were
registered. RESULTS: In-hospital mortality was 3.9 % (versus 0.9 % mortality
among 17,740 patients without CVD). Cardiovascular complications occurred in 91
(7.6 %) patients (with 37.4 % case fatality). Perioperative bleeding occurred in
160 (13.3 %) patients and was fatal in 2 (1.2 % case fatality). Multivariate
analysis revealed age, preoperative anaemia, history of chronic heart failure,
acute surgery and general anaesthesia predictive of cardiovascular complications.
For bleeding complications multivariate analysis found warfarin use in the last 3
days, history of hypertension and general anaesthesia as independent predictive
factors. Aspirin interruption before surgery was not predictive for either
cardiovascular or for bleeding complications. CONCLUSIONS: Perioperative
cardiovascular complications in these high-risk elderly all-comer surgical
patients with known cardiovascular disease are relatively rare, but once they
occur, the case fatality is high. Perioperative bleeding complications are more
frequent, but their case fatality is extremely low. Patterns of interruption of
chronic aspirin therapy before major non-cardiac surgery are not predictive for
perioperative complications (neither cardiovascular, nor bleeding). Simple
baseline clinical factors are better predictors of outcomes than antithrombotic
drug interruption patterns.
PMID- 25120212
TI - Prognostic value of microvolt T-wave alternans in a real-world ICD population.
Twente ICD Cohort Studie (TICS).
AB - INTRODUCTION: Survival benefit from ICD implantation is relatively low in primary
prevention patients. Better patient selection is important to maintain maximum
survival benefit while reducing the number of unnecessary implants. Microvolt T
wave alternans (MTWA) is a promising risk marker. In this study, we aimed to
evaluate the predictive value of MTWA in ICD patients. METHODS AND RESULTS: This
study was a substudy of the Twente ICD Cohort Study (TICS). Patients with
ischaemic or non-ischaemic left ventricular dysfunction who received an ICD
following current ESC guidelines were eligible for inclusion. Exercise-MTWA was
performed and classified as non-negative or negative. The primary endpoint was
the composite of mortality and appropriate shock therapy. Analysis was performed
in 134 patients (81 % male, mean age 62 years, mean ejection fraction 26.5 %).
MTWA was non-negative in 64 %. There was no relation between non-negative MTWA
testing and mortality and/or appropriate shock therapy (all p-values >0.15). Due
to clinical conditions, 24 % were ineligible for testing. These patients
experienced the highest risk for mortality (p < 0.01). CONCLUSION: Non-negative
MTWA testing did not predict mortality and/or appropriate shock therapy.
Furthermore, MTWA testing is not feasible in a large percentage of patients.
These ineligible patients experience the highest risk for mortality.
PMID- 25120213
TI - Trait mindfulness and autobiographical memory specificity.
AB - Training in mindfulness skills has been shown to increase autobiographical memory
specificity. The aim of this study was to examine whether there is also an
association between individual differences in trait mindfulness and memory
specificity using a non-clinical student sample (N = 70). Also examined were the
relationships between other memory characteristics and trait mindfulness, self
reported depression and rumination. Participants wrote about 12 autobiographical
memories, which were recalled in response to emotion word cues in a minimal
instruction version of the Autobiographical Memory Test, rated each memory for
seven characteristics, and completed the Freiburg Mindfulness Inventory, the
Depression, Anxiety, and Stress Scale, and the Ruminative Responses Scale. Higher
rumination scores were associated with more reliving and more intense emotion
during recall. Depression scores were not associated with any memory variables.
Higher trait mindfulness was associated with lower memory specificity and with
more intense and more positive emotion during recall. Thus, trait mindfulness is
associated with memory specificity, but the association is opposite to that found
in mindfulness training studies. It is suggested that this difference may be due
to an influence of trait mindfulness on memory encoding as well as retrieval
processes and an influence on the mode of self-awareness that leads to a greater
focus on momentary rather than narrative self-reference.
PMID- 25120215
TI - Can immunostimulants efficiently replace antibiotic in striped catfish
(Pangasianodon hypophthalmus) against bacterial infection by Edwardsiella
ictaluri?
AB - The present study was performed to determine the efficacy of lipopolysaccharide
(LPS) and levamisole on immune response and disease resistance in striped catfish
and to compare their respective efficiency with the one of an antibiotic
treatment after infection of fish by the bacteria Edwardsiella ictaluri. Fish
were divided into 3 groups and each group was injected with LPS (3 mg/kg fish),
levamisole (5 mg/kg fish) or phosphate buffer saline as control. At day 21st post
immunostimulant injection, fish were bled for assaying immunological variables
and then challenged with E. ictaluri. Three days after bacterial infection, an
antibiotic treatment was applied into fish subgroups and mortality was compared
daily between antibiotic treated and untreated fish until 2 weeks post-challenge.
LPS and levamisole significantly enhanced non-specific immune responses such as
respiratory burst, lysozyme and complement activity in fish compared with control
(p < 0.05). Respiratory burst and complement activity significantly increased in
levamisole groups when compared with LPS groups while lysozyme activity did not
differ significantly between immunostimulant treatments. Total immunoglobulins
significantly increased in levamisole treatment compared with control. After
challenge test, accumulated mortality was reduced significantly in both non
antibiotic and antibiotic subgroups of LPS and levamisole compared with control.
Moreover, no differences of mortality were observed between fish treated with
levamisole or LPS without antibiotics and control fish treated with antibiotics.
These results support the possible replacement of antibiotics in striped catfish
farming by immunostimulants such as levamisole and LPS.
PMID- 25120214
TI - Epidermal growth factor receptor and KRAS mutations in lung adenocarcinoma: a
retrospective study of the Lebanese population.
AB - Molecular genetic analysis of epidermal growth factor receptor (EGFR) and Kirsten
rat sarcoma viral oncogene (KRAS) mutations in lung adenocarcinoma has become an
integral part of lung cancer diagnosis and treatment; however, their prevalence
varies with ethnicity. Little is know concerning their prevalence in Arab
populations. In the present study, mutational analysis for EGFR and KRAS was
performed on two cohorts of the Lebanese population. Lung adenocarcinoma cases
(106) underwent mutational analysis for KRAS in exon 2, codon 12 and 13 and exon
3 codon 61 by reverse hybridization using the KRAS 12/13/61 StripAssay(r).
Subsequently, cases with no KRAS mutations underwent EGFR mutational analysis
using the EGFR RGQ polymerase chain reaction (PCR) kits for real-time PCR on the
Rotor-Gene Q 5-plex HRM. KRAS mutations were detected in 37.7% of 106 lung
adenocarcinomas; 85% had a G>T substitution in codon 12 and 13 of exon 2, and
8.5% had EGFR mutations with exon 19 deletions (88.9%) and one case with L858R
substitution in exon 21. EGFR mutations were significantly correlated with
females, non-smokers and well differentiation of the tumor. This is the first
study in an Arab population that reports the prevalence of both EGFR and KRAS
gene mutations in lung adenocarcinoma using very sensitive mutational analysis
techniques. Therefore, EGFR reflex testing should be implemented in the
management of lung adenocarcinomas, while KRAS testing must await the
identification of effective targeted therapy.
PMID- 25120216
TI - Characteristic and functional analysis of a ficolin-like protein from the oyster
Crassostrea hongkongensis.
AB - Ficolins are a group of soluble animal proteins with multiple roles in innate
immunity. These proteins recognize and bind carbohydrates in pathogens and
activate the complement system, leading to opsonization, leukocyte activation,
and direct pathogen killing, which have been reported in many animal species but
might not be present in the shellfish lineage. In the present study, we
identified the first fibrinogen-related protein from the oyster, Crassostrea
hongkongensis. This novel ficolin-like protein contains a typical signal peptide
and a fibrinogen-related domain (designated ChFCN) at the N and C termini,
respectively, but does not contain the additional collagen-like domain of
ficolins. The full-length cDNA of ChFCN is 1105 bp, encoding a putative protein
of 297 amino acids with the molecular weight of 35.5 kD. ChFCN is ubiquitously
expressed in selected tissues, with the highest expression level observed in the
gills. The temporal expression of ChFCN following microbe infection shows that
the expression of ChFCN in hemocytes increases at 3 h post-challenge. The ChFCN
protein expression was also examined, and fluorescence microscopy revealed that
deChFCN (truncated signal peptide) is located in the cytoplasm of HeLa cells.
Full-length ChFCN was detected in the medium supernatant by western blot
analysis. Recombinant ChFCN proteins with the molecular weight about 50 kD bind
Saccharomyces cerevisiae, Staphylococcus haemolyticus or Escherichia coli K-12,
but not those from Vibrio alginolyticus. Furthermore, the rChFCN protein could
agglutinate Gram-negative bacteria E. coli K-12 and enhance the phagocytosis of
C. hongkongensis hemocytes in vitro. These results indicate that ChFCN might play
an important role in the immunity response of oysters.
PMID- 25120217
TI - Molecular cloning and characterization of high mobility group box1 (Ls-HMGB1)
from humphead snapper, Lutjanus sanguineus.
AB - High mobility group box1 (HMGB1) is a kind of chromatin-associated nonhistone
protein important for nucleosome formation, transcriptional regulation and
inflammation. However, the reports about HMGB1 of marine fish were still limited.
Here, we cloned and characterized a HMGB1 gene from humphead snapper, Lutjanus
sanguineus (Ls-HMGB1). The Ls-HMGB1 cDNA composed of 1199 bp with a 70 bp of 5'
UTR, 630 bp open reading frame (ORF) and 499 bp 3'-UTR, encoded a polypeptide of
210 amino acids (GenBank Accession No: KJ783442). Sequence alignment of Ls-HMGB1
showed the highest similarity of 91% with Sciaenops ocellatus HMGB1 protein.
Quantitative real-time PCR (qRT-PCR) analysis revealed that Ls-HMGB1 had
relatively high expression level in skin, kidney and heart. After Vibrio harveyi
and poly I:C stimulation, transcripts of Ls-HMGB1 were significantly increased
and reached to peak at 18 h p.i. The L. sanguineus interleukin-6 (Ls-IL6)
transcription in HK leukocytes was significantly induced by recombinant LsHMGB1
(rLsHMGB1). These results indicated that Ls-HMGB1 may play an important role in
immune response of L. sanguineus during pathogen challenge.
PMID- 25120218
TI - N-acetylglucosamine enhances survival ability of tilapias infected by
Streptococcus iniae.
AB - Streptococcus iniae infection has emerged as a serious fish health and economic
problem in the global aquaculture operations. Current antibiotic options are few
and possess severe practical limitations and potential adverse environmental
impacts. The major factor contributing to the large burden of S. iniae disease in
aquaculture is the lack of fundamental knowledge of innate immunity against the
pathogen. In the present study, we use a tilapia model to explore which
metabolites are crucial for the defense against the infection caused by S. iniae.
We establish GC/MS based metabolic profile of tilapia liver and then compare the
metabolic difference between survivals and the dying fish post the bacterial
infection. We identify elevating N-acetylglucosamine in survival group as the
most crucial metabolite differentiating the survivals from the dying in these
fish infected by S. iniae. Exogenous N-acetylglucosamine significantly elevates
survival ability of tilapia against the infection caused by S. iniae. Our
findings highlight the importance of metabolic strategy against bacterial
infections.
PMID- 25120219
TI - Inducible and constitutive expression of an elicitor gene Hrip1 from Alternaria
tenuissima enhances stress tolerance in Arabidopsis.
AB - Hrip1 is a novel hypersensitive response-inducing protein secreted by Alternaria
tenuissima that activates defense responses and systemic acquired resistance in
tobacco. This study investigates the role that Hrip1 plays in responses to
abiotic and biotic stress using transgenic Arabidopsis thaliana expressing the
Hrip1 gene under the control of the stress-inducible rd29A promoter or
constitutive cauliflower mosaic virus 35S promoter. Bioassays showed that
inducible Hrip1 expression in rd29A?Hrip1 transgenic lines had a significantly
higher effect on plant height, silique length, plant dry weight, seed germination
and root length under salt and drought stress compared to expression in 35S?Hrip1
lines and wild type plants. The level of enhancement of resistance to Botrytis
cinerea by the 35S?Hrip1 lines was higher than in the rd29A?Hrip1 lines.
Moreover, stress-related gene expression in the transgenic Arabidopsis lines was
significantly increased by 200 mM NaCl and 200 mM mannitol treatments, and
defense genes in the jasmonic acid and ethylene signaling pathway were
significantly up-regulated after Botrytis inoculation in the Hrip1 transgenic
plants. Furthermore, the activity of some antioxidant enzymes, such as peroxidase
and catalase increased after salt and drought stress and Botrytis infection.
These results suggested that the Hrip1 protein contributes to abiotic and biotic
resistance in transgenic Arabidopsis and may be used as a useful gene for
resistance breeding in crops. Although the constitutive expression of Hrip1 is
suitable for biotic resistance, inducible Hrip1 expression is more responsive for
abiotic resistance.
PMID- 25120220
TI - A complex RARE is required for the majority of Nedd9 embryonic expression.
AB - Neural precursor cell expressed, developmentally down-regulated 9 (Nedd9, Casl,
Hef1, p105cas, Ef1) is a scaffolding protein that assembles complexes involved in
regulating cell adhesion, migration, division, and survival. Nedd9 is found very
early in the developing embryonic nervous system. A highly conserved complex
retinoic acid response element (RARE) is located 485 base pairs (bp) upstream of
exon 2B in the promoter of the Nedd9 gene. Mice transgenic for a 5.2 kilobase
(kb) region of the 2B Nedd9 promoter containing the RARE upstream of a lacZ
reporter gene [Nedd9(RARE)-lacZ] show a large subset of the normal endogenous
Nedd9 expression including that in the caudal hindbrain neuroepithelium, spinal
cord, dorsal root ganglia (drg) and migrating neural crest (ncc). However, the
transgenic mice do not recapitulate the native Nedd9 expression pattern in
presumptive rhombomeres (pr) 3 and 5 of the early hindbrain, the base of the
neuroepithelium in the midbrain, nor the forebrain telencephalon. Thus, the 5.2
kb region containing the intact RARE drives a large subset of Nedd9 expression,
with additional sequences outside of this region needed to define the full
complement of expression. When the 5.2 kb construct is modified (eight point
mutations) to eliminate responsiveness of the RARE to all-trans retinoic acid
(atRA) [Nedd9(mutRARE)-lacZ], virtually all beta-galactosidase (beta-gal, lacZ)
expression is lost. Exposure of Nedd9(RARE)-lacZ transgenic embryos to excess
atRA at embryonic day 8.0 (E8.0) leads to rostral ectopic transgene expression
within 6 h whereas the Nedd9(mutRARE)-lacZ mutant does not show this effect. Thus
the RARE upstream of the Nedd9 2B promoter is necessary for much of the
endogenous gene expression during early development as well as ectopic expression
in response to atRA.
PMID- 25120221
TI - Imaging spectrum of peritoneal carcinomatosis on FDG PET/CT.
AB - Recognition of patterns has always been extremely important in cross-sectional
imaging. Peritoneal involvement, both primary and as dissemination from
abdominopelvic malignancies, is manifested in different forms, purely because of
anatomical complexity. We studied series of peritoneal involvement by (18)F
fluorodeoxyglucose positron-emission tomography/computed tomography fusion
imaging and derived patterns of tracer uptake on maximum intensity projection and
cross-sectional fusion images.
PMID- 25120222
TI - PTP1B inhibitors for type 2 diabetes treatment: a patent review (2011 - 2014).
AB - INTRODUCTION: Protein tyrosine phosphatase 1B (PTP1B) plays an important role in
the negative regulation of insulin signal transduction pathway and has emerged as
novel therapeutic strategy for the treatment of type 2 diabetes. PTP1B inhibitors
enhance the sensibility of insulin receptor (IR) and have favorable curing effect
for insulin resistance-related diseases. A large number of PTP1B inhibitors,
either synthetic or isolated as bioactive agents from natural products, have
developed and investigated for their ability to stimulate insulin signaling.
AREAS COVERED: This review includes an updated summary (2011 - 2014) of PTP1B
inhibitors that have been published in patent applications, with an emphasis on
their chemical structure, mode of action and therapeutic outcomes. The usefulness
of PTP1B inhibitors as pharmaceutical agents for the treatment of type 2 diabetes
is also discussed. EXPERT OPINION: PTP1B inhibitors show beneficial effects to
enhance sensibility of IR by restricting the activity of enzyme and have
favorable curing effects. However, structural homologies in the catalytic domain
of PTP1B with other protein tyrosine phosphatases (PTPs) like leukocyte common
antigen-related, CD45, SHP-2 and T-cell-PTP present a challenging task of
achieving selectivity. Thus, for therapeutic application of PTP1B inhibitors,
highly selective molecules exhibiting desired effects without side effects are
expected to find clinical application.
PMID- 25120224
TI - Magnetic steering control of multi-cellular bio-hybrid microswimmers.
AB - Bio-hybrid devices, which integrate biological cells with synthetic components,
have opened a new path in miniaturized systems with the potential to provide
actuation and control for systems down to a few microns in size. Here, we address
the challenge of remotely controlling bio-hybrid microswimmers propelled by
multiple bacterial cells. These devices have been proposed as a viable method for
targeted drug delivery but have also been shown to exhibit stochastic motion. We
demonstrate a method of remote magnetic control that significantly reduces the
stochasticity of the motion, enabling steering control. The demonstrated
microswimmers consist of multiple Serratia marcescens (S. marcescens) bacteria
attached to a 6 MUm-diameter superparamagnetic bead. We characterize their motion
and define the parameters governing their controllability. We show that the
microswimmers can be controlled along two-dimensional (2-D) trajectories using
weak magnetic fields (<=10 mT) and can achieve 2-D swimming speeds up to 7.3 MUm
s(-1). This magnetic steering approach can be integrated with sensory-based
steering in future work, enabling new control strategies for bio-hybrid
microsystems.
PMID- 25120223
TI - Disruption of resting functional connectivity in Alzheimer's patients and at-risk
subjects.
AB - The resting brain exhibits continuous intrinsic activity, which is correlated
between groups of regions forming resting state networks. Evaluating resting
connectivity is a popular approach for studying brain diseases. Several hundred
studies are now available that address integrity of resting connectivity in
patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), as
well as preclinical at-risk subjects. Most studies focus on the default mode
network, a system of specific brain areas showing strong connected resting
activity that attenuates during goal-directed behavior. The extent of intrinsic
brain activity tends to be strongly correlated with cognitive processes and is
specifically disrupted in AD and MCI patients and at-risk subjects, with changes
seeming to evolve during the transition between the disease stages. In this
study, we review the current findings in default mode network and other resting
state network studies in AD and MCI patients and at-risk subjects as assessed by
resting state functional magnetic resonance imaging.
PMID- 25120225
TI - Fast and mild strategy, using superhydrophobic surfaces, to produce
collagen/platelet lysate gel beads for skin regeneration.
AB - Platelet lysate (PL) was encapsulated in collagen (Coll) millimetric gel beads,
on biomimetic superhydrophobic surfaces, under mild conditions, with the aim of
obtaining easy-to-handle formulations able to provide sustained release of
multiple growth factors for skin ulcers treatment. The gel particles were
prepared with various concentrations of PL incorporating or not stem cells, and
tested as freshly prepared or after being freeze-dried or cryopreserved. Coll +
PL particles were evaluated regarding degradation in collagenase-rich environment
(simulating the aggressive environment of the chronic ulcers), sustained release
of total protein, PDGF-BB and VEGF, cell proliferation (using particles as the
only source of growth factors), scratch wound recovery and angiogenic capability.
Compared to Coll solely particles, incorporation of PL notably enhanced cell
proliferation (inside and outside gels) and favored scratch wound recovery and
angiogenesis. Moreover, cell-laden gel particles containing PL notably improved
cell proliferation and even migration of cells from one particle towards a
neighbor one, which led to cell-cell contacts and the spontaneous formation of
tissue layers in which the spherical gels were interconnected by the stem cells.
PMID- 25120228
TI - Perceptions of mailed HPV self-testing among women at higher risk for cervical
cancer.
AB - Whether human papillomavirus (HPV) self-testing can expand access to cervical
cancer screening will depend on making the test accessible and acceptable to
higher-risk women. To evaluate a novel delivery mode, we mailed HPV self-test
kits to low-income, under-screened women and assessed their perceptions of self
testing and cervical cancer prevention. We conducted a telephone survey of 199
women in North Carolina. Eligibility criteria included not having had a Pap test
in 4 years and reporting 1 or more indicators of economic hardship, such as being
uninsured. Over half (55 %) of women in the diverse sample were non-Hispanic
black, and almost three-quarters (74 %) reported annual household incomes of
$20,000 or less. Trust in HPV self-testing was moderate to high, with almost all
women (98 %) agreeing the mailed test was safe. A few women (6 %) preferred HPV
self-testing to Pap testing for protecting health, but most (75 %) had no
preference. Trust in or preference for mailed self-testing did not vary by race
or income. However, compared to white women, black women had lower HPV-related
knowledge (OR 0.46, 95 % CI 0.23-0.92) and perceived lower cervical cancer risk
in the absence of screening (OR 0.44, 95 % CI 0.22-0.86). We found similar
patterns of disparities for women with very low (<$10,000) versus relatively
higher incomes. Our findings suggest that, across racial and economic subgroups,
under-screened women generally trust HPV self-tests delivered by mail. To
succeed, programs for HPV self-testing must overcome disparities in knowledge and
perceptions related to cervical cancer screening.
PMID- 25120229
TI - Evaluation of the National HIV Behavioral Surveillance System among men who have
sex with men in Denver, Colorado.
AB - Denver Public Health implements the National HIV Behavioral Surveillance System
(NHBS), a cyclical survey of populations at increased risk for HIV. We evaluated
the implementation of NHBS among Denver men who have sex with men (MSM),
considering the system's simplicity, data quality, representativeness, and
sensitivity to trends. We found that the time required for implementation and the
complexity of data management and analysis are barriers to disseminating local
findings. Data quality has improved in each cycle of the study but must be
protected by continually checking for errors and training field staff to be
attentive to detail. Compared with the US census and other convenience samples of
Denver MSM, the overall demographic representativeness of NHBS has improved over
time. However, there is concern that the underlying population included in the
study may be changing. NHBS survey data show evidence of two suspected trends in
the local MSM population at risk for HIV: increasing sexual risk-taking and the
transition away from bars as a dominant partner-finding location. It is unclear
whether the increasing reports of sexual risk-taking reflect a real trend or
simply a change in the population sampled, since most NHBS participants are
recruited at gay bars and other venues. To ensure that the sample continues to
represent the underlying population at risk and accurately identify trends, it is
necessary to closely monitor MSM sample characteristics during implementation and
incorporate weighted data provided by the Centers for Disease Control and
Prevention into analyses.
PMID- 25120230
TI - Medication use in community-residing older adults in Taiwan: a comparison between
conventional and complementary and alternative medications.
AB - Older adults are at risk of problems of medication use including underuse,
overuse, and misuse. The purposes of this study were to investigate the
prevalence of the use of conventional and complementary and alternative
medications (CAM) in older adults and to explore which factors related to their
medication use. For this descriptive correlational study, 1,427 citizens who were
65 years old or older from two towns in Yilan County, Taiwan were interviewed by
ten trained public health nurses between June and September, 2013. Instruments in
this study were physical functional capacity, depressive symptoms, and medication
use. Pearson product-moment correlation analysis and the Chi-square test were
used to detect relationships among research variables. Of the 1,427 participants,
75.4 % used at least one type of conventional medication, and the average number
of medications used was 2.9 (SD = 2.1). Polypharmacy (the use of five or more
medications) was identified in 20.1 % of participants. Significant factors
related to conventional medications use were older age (chi(2) = 41.7***), female
(chi(2) = 7.6**), bad memory (chi(2) = 11.2**), defect cognition status (chi(2) =
7.8**), lost the interest to do anything depressive symptoms (chi(2) = 7.2**),
and independent in their daily activities (chi(2) = 41.3***). We found that
sociodemographic characteristics and factors pertaining to health status
determine the difference between the use of conventional medications and CAM by
rural older adults. Our study results suggested that health professionals in
Taiwan must be educated and trained in how to integrate CAM into current
conventional treatment.
PMID- 25120227
TI - A review of OROS methylphenidate (Concerta((r))) in the treatment of attention
deficit/hyperactivity disorder.
AB - Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioural
disorder with onset during childhood. It affects a child's development, both at
home and at school, and impacts on social, emotional and cognitive functioning,
in both the home and the school environment. Untreated ADHD is very often
associated with poor academic achievement, low occupational status, increased
risk of substance abuse and delinquency. Current practice guidelines recommend a
multimodal approach in the treatment of ADHD, which includes educational,
behavioural and mental health interventions, and pharmacological management.
Stimulant medications, including methylphenidate (MPH) and amphetamine products,
are recommended as first-line pharmacotherapy in the treatment of ADHD. The
choice of stimulant is influenced by several factors; the most influential factor
is the duration of action. Long-acting medication provides benefits long after
school and work. It also increases the likelihood of once-daily dosing, thereby
eliminating the need for mid-day dosing, making the treatment more private,
avoiding stigma and improving adherence to medication. MPH is the most widely
used psychotropic medication in child psychiatry. It was first developed for use
in children as an oral, immediate-release formulation and more recently as
various extended-release formulations. These latter formulations include the 12 h
preparation Concerta((r)) (osmotic-release oral system [OROS] MPH), which
utilizes an osmotic pump system, designed to overcome the difficulties of
multiple daily dosing. Since it received approval from the US Food and Drug
Administration in August 2000, OROS MPH has been quickly and widely accepted as
one of the preferred treatments for ADHD because of its once-daily dosing. This
paper reviews the data in support of long-acting OROS MPH in children,
adolescents and adults, both in ADHD and in association with its comorbidities.
PMID- 25120226
TI - Human adipose-derived mesenchymal stem cells improve motor functions and are
neuroprotective in the 6-hydroxydopamine-rat model for Parkinson's disease when
cultured in monolayer cultures but suppress hippocampal neurogenesis and
hippocampal memory function when cultured in spheroids.
AB - Adult human adipose-derived mesenchymal stem cells (MSC) have been reported to
induce neuroprotective effects in models for Parkinson's disease (PD). However,
these effects strongly depend on the most optimal application of the transplant.
In the present study we compared monolayer-cultured (aMSC) and spheroid (sMSC)
MSC following transplantation into the substantia nigra (SN) of 6-OHDA lesioned
rats regarding effects on the local microenvironment, degeneration of
dopaminergic neurons, neurogenesis in the hippocampal DG as well as motor and
memory function in the 6-OHDA-rat model for PD. aMSC transplantation
significantly increased tyrosine hydroxylase (TH) and brain-derived neurotrophic
factor (BDNF) levels in the SN, increased the levels of the glial fibrillary
acidic protein (GFAP) and improved motor functions compared to untreated and sMSC
treated animals. In contrast, sMSC grafting induced an increased local
microgliosis, decreased TH levels in the SN and reduced numbers of newly
generated cells in the dentate gyrus (DG) without yet affecting hippocampal
learning and memory function. We conclude that the neuroprotective potential of
adipose-derived MSC in the rat model of PD crucially depends on the applied
cellular phenotype.
PMID- 25120231
TI - Comparisons of tunnel-graft angle and tunnel length and position between
transtibial and transportal techniques in anterior cruciate ligament
reconstruction.
AB - PURPOSE: Our aim was to evaluate tunnel-graft angle, tunnel length and position
and change in graft length between transtibial (30 patients) and anteromedial (30
patients) portal techniques using 3D knee models after anterior cruciate ligament
(ACL) reconstruction. METHODS: The 3D angle between femoral or tibial tunnels and
graft at 0 degrees and 90 degrees flexion were compared between groups. We
measured tunnel lengths and positions and evaluated the change in graft length
from 0 degrees to 90 degrees flexion. RESULTS: The 3D angle at the femoral
tunnel with graft showed a significant difference between groups at 0 degrees
flexion (p = 0.01) but not at 90 degrees flexion (p = 0.12). The 3D angle of the
tibial tunnel showed no significant differences between groups. Femoral tunnel
length in the transtibial group was significantly longer than in the transportal
group (40.7 vs 34.7 mm,), but tibial tunnel length was not. The relative height
of the lateral femoral condyle was significantly lower in the transportal than
the transtibial group (24.1% vs 34.4%). No significant differences were found
between groups in terms of tibial tunnel position. The change in graft length
also showed no significant difference between groups. CONCLUSION: Even though the
transportal technique in ACL reconstruction can place the femoral tunnel in a
better anatomical position than the transtibial technique, it has risks of a
short femoral tunnel and acute angle at the femoral tunnel. Moreover, there was
also no difference in the change of the graft length between groups.
PMID- 25120232
TI - Full-thickness supraspinatus tendon tears: correlation of findings by arthroscopy
and magnetic resonance imaging.
AB - PURPOSE: The main aim of this study was to correlate measurements of the width
and retraction of isolated full-thickness supraspinatus tendon tears determined
by magnetic resonance imaging (MRI) with measurements recorded by arthroscopy
using a continuous millimetre scale. METHODS: A total of 53 individuals with
isolated supraspinatus tears and retraction < 30 mm underwent arthroscopy at our
centre. Tear width and retraction measured by arthroscopy (reference standard)
and MRI (index test) on a continuous millimetre scale were compared. All
measurements were performed by a single radiologist blinded to intra-operative
findings and one surgeon who had previous access to MRI results. RESULTS: The
average tear retraction was 12.60 +/- 4.89 mm by arthroscopy and 16.81 +/- 6.29
mm by MRI. Those measures exhibited moderate correlation (r = 0.643, p < 0.001)
and an average difference of 4.21 mm (p < 0.001). Average tear width was 12.87 +/
4.15 mm by arthroscopy and 14.19 +/- 5.20 by MRI. Those measures exhibited
moderate correlation (r = 0.526, p < 0.001) and an average difference of 1.32 mm,
which was not statistically significant (p = 0.109). CONCLUSION: Measures of
retraction and width obtained by MRI and arthroscopy exhibited moderate
correlation in small- or medium-sized supraspinatus tears.
PMID- 25120233
TI - Latent tuberculosis reactivation in a patient with erythrodermic psoriasis under
treatment with ustekinumab and a low dose steroid, despite isoniazid
chemoprophylaxis.
PMID- 25120236
TI - Graph theoretical analysis on the kinetic rate equations of linear chain and
cyclic reaction networks.
AB - Graph theoretical solutions for kinetic rate equations of some reaction networks
involving linear chains and cycles have been derived; condensation polymerization
and long chain of radioactive decay come under the purview of the former whereas
the interconversion of the species in cycles under the later. The reactions for
the linear chains considered here proceed monotonically to the steady states with
time whereas the cycle with all irreversible steps has been found to have either
periodic or monotonic time evaluation of concentrations depending on the values
of rate constants of the involved paths. In case of a cyclic reaction having all
reversible paths, the condition for the microscopic reversibility has been
derived on the basis of the assumption that the decay constants obtained for this
case are all real.
PMID- 25120235
TI - Ophthalmologic complications after intraoral local anesthesia.
AB - INTRODUCTION: The first ophthalmologic complication in conjunction with a dental
anesthesia was reported in 1936. The objective of the present study was a
detailed analysis of case reports about that topic. MATERIAL AND METHODS: After
conducting a literature search in PubMed this study analyzed 108 ophthalmologic
complications following intraoral local anesthesia in 65 case reports with
respect to patient-, anesthesia-, and complication- related factors. RESULTS: The
mean age of the patients was 33.8 years and females predominated (72.3%). The
most commonly reported complication was diplopia (39.8%), mostly resulting from
paralysis of the lateral rectus muscle. Other relatively frequent complications
included ptosis (16.7%), mydriasis (14.8%) and amaurosis (13%). Ophthalmologic
complications were mainly associated with block anesthesia of the inferior
alveolar nerve (45.8%) or the posterior superior alveolar nerve (40.3%).
Typically, the ophthalmologic complications in conjunction with intraoral local
anesthesia had an immediate to short onset, and disappeared as the anesthesia
subsided. DISCUSSION AND CONCLUSION: The increased number of ophthalmologic
complications after intraoral local anesthesia in females may suggest a gender
effect. Double vision (diplopia) is the most frequently described complication,
which is usually completely reversible like the other reported ophthalmologic
complications.
PMID- 25120234
TI - Sequencing, physical organization and kinetic expression of the patulin
biosynthetic gene cluster from Penicillium expansum.
AB - Patulin is a polyketide-derived mycotoxin produced by numerous filamentous fungi.
Among them, Penicillium expansum is by far the most problematic species. This
fungus is a destructive phytopathogen capable of growing on fruit, provoking the
blue mold decay of apples and producing significant amounts of patulin. The
biosynthetic pathway of this mycotoxin is chemically well-characterized, but its
genetic bases remain largely unknown with only few characterized genes in less
economic relevant species. The present study consisted of the identification and
positional organization of the patulin gene cluster in P. expansum strain NRRL
35695. Several amplification reactions were performed with degenerative primers
that were designed based on sequences from the orthologous genes available in
other species. An improved genome Walking approach was used in order to sequence
the remaining adjacent genes of the cluster. RACE-PCR was also carried out from
mRNAs to determine the start and stop codons of the coding sequences. The patulin
gene cluster in P. expansum consists of 15 genes in the following order: patH,
patG, patF, patE, patD, patC, patB, patA, patM, patN, patO, patL, patI, patJ, and
patK. These genes share 60-70% of identity with orthologous genes grouped
differently, within a putative patulin cluster described in a non-producing
strain of Aspergillus clavatus. The kinetics of patulin cluster genes expression
was studied under patulin-permissive conditions (natural apple-based medium) and
patulin-restrictive conditions (Eagle's minimal essential medium), and
demonstrated a significant association between gene expression and patulin
production. In conclusion, the sequence of the patulin cluster in P. expansum
constitutes a key step for a better understanding of the mechanisms leading to
patulin production in this fungus. It will allow the role of each gene to be
elucidated, and help to define strategies to reduce patulin production in apple
based products.
PMID- 25120237
TI - Identification of atomic-level mechanisms for gas-phase X- + CH3Y SN2 reactions
by combined experiments and simulations.
AB - For the traditional model of gas-phase X(-) + CH3Y SN2 reactions, C3v ion-dipole
pre- and postreaction complexes X(-)---CH3Y and XCH3---Y(-), separated by a
central barrier, are formed. Statistical intramolecular dynamics are assumed for
these complexes, so that their unimolecular rate constants are given by RRKM
theory. Both previous simulations and experiments have shown that the dynamics of
these complexes are not statistical and of interest is how these nonstatistical
dynamics affect the SN2 rate constant. This work also found there was a
transition from an indirect, nonstatistical, complex forming mechanism, to a
direct mechanism, as either the vibrational and/or relative translational energy
of the reactants was increased. The current Account reviews recent collaborative
studies involving molecular beam ion-imaging experiments and direct (on-the-fly)
dynamics simulations of the SN2 reactions for which Cl(-), F(-), and OH(-) react
with CH3I. Also considered are reactions of the microsolvated anions OH(-)(H2O)
and OH(-)(H2O)2 with CH3I. These studies have provided a detailed understanding
of the atomistic mechanisms for these SN2 reactions. Overall, the atomistic
dynamics for the Cl(-) + CH3I SN2 reaction follows those found in previous
studies. The reaction is indirect, complex forming at low reactant collision
energies, and then there is a transition to direct reaction between 0.2 and 0.4
eV. The direct reaction may occur by rebound mechanism, in which the ClCH3
product rebounds backward from the I(-) product or a stripping mechanism in which
Cl(-) strips CH3 from the I atom and scatters in the forward direction. A similar
indirect to direct mechanistic transition was observed in previous work for the
Cl(-) + CH3Cl and Cl(-) + CH3Br SN2 reactions. At the high collision energy of
1.9 eV, a new indirect mechanism, called the roundabout, was discovered. For the
F(-) + CH3I reaction, there is not a transition from indirect to direct reaction
as Erel is increased. The indirect mechanism, with prereaction complex formation,
is important at all the Erel investigated, contributing up ~60% of the reaction.
The remaining direct reaction occurs by the rebound and stripping mechanisms.
Though the potential energy curve for the OH(-) + CH3I reaction is similar to
that for F(-) + CH3I, the two reactions have different dynamics. They are akin,
in that for both there is not a transition from an indirect to direct reaction.
However, for F(-) + CH3I indirect reaction dominates at all Erel, but it is less
important for OH(-) + CH3I and becomes negligible as Erel is increased. Stripping
is a minor channel for F(-) + CH3I, but accounts for more than 60% of the OH(-) +
CH3I reaction at high Erel. Adding one or two H2O molecules to OH(-) alters the
reaction dynamics from that for unsolvated OH(-). Adding one H2O molecule
enhances indirect reaction at low Erel, and changes the reaction mechanism from
primarily stripping to rebound at high Erel. With two H2O molecules the dynamics
is indirect and isotropic at all collision energies.
PMID- 25120238
TI - Anti-inflammatory effects of vitamin E on adjuvant-induced arthritis in rats.
AB - Vitamin E (vit-E) is a lipophilic antioxidant, and its anti-inflammatory activity
is still not full characterized. Thus, our goal was to investigate the anti
inflammatory effect of repeated vit-E treatment in the arthritis induced by the
intraplantar injection of complete Freund's adjuvant (CFA). We observed an
increase in arthritis scores, interleukin-1beta and H2O2 levels, neutrophil and
macrophage infiltration, thermal hyperalgesia, mechanical allodynia, and loss of
function induced by intraplantar CFA injection. These effects were unaltered
after 1 day, partially reversed after 3 days, and inhibited after 9 days after
vit-E treatment. Furthermore, the concentration of vit-E was reduced and that of
tumor necrosis factor-alpha was increased in the CFA-injected paw. Both effects
were reversed from 1 to 9 days after vit-E treatment. However, vit-E treatment
did not alter CFA-induced edema at any time. Thus, vit-E treatment produced an
anti-inflammatory effect of slow onset in CFA, which demonstrates a disease
modifying drug profile.
PMID- 25120240
TI - Why does guessing incorrectly enhance, rather than impair, retention?
AB - The finding that trying, and failing, to predict the upcoming to-be-remembered
response to a given cue can enhance later recall of that response, relative to
studying the intact cue-response pair, is surprising, especially given that the
standard paradigm (e.g., Kornell, Hays, & Bjork, 2009) involves allocating what
would otherwise be study time to generating an error. In three experiments, we
sought to eliminate two potential heuristics that participants might use to aid
recall of correct responses on the final test and to explore the effects of
interference both at an immediate and at a delayed test. In Experiment 1, by
intermixing strongly associated to-be-remembered pairs with weakly associated
pairs, we eliminated a potential heuristic participants can use on the final test
in the standard version of the paradigm-namely, that really strong associates are
incorrect responses. In Experiment 2, by rigging half of the participants'
responses to be correct, we eliminated another potential heuristic-namely, that
one's initial guesses are virtually always wrong. In Experiment 3, we examined
whether participants' ability to remember-and discriminate between-their
incorrect guesses and correct responses would be lost after a 48-h delay, when
source memory should be reduced. Across all experiments, we continued to find a
robust benefit of trying to guess to-be-learned responses, even when incorrect,
versus studying intact cue-response pairs. The benefits of making incorrect
guesses are not an artifact of the paradigm, nor are they limited to short
retention intervals.
PMID- 25120241
TI - Testing can counteract proactive interference by integrating competing
information.
AB - Testing initially learned information before presenting new information has been
shown to counteract the deleterious effects of proactive interference by
segregating competing sources of information. The present experiments were
conducted to demonstrate that testing can also have its effects in part by
integrating competing information. Variations of classic A-B, A-D paired
associate learning paradigms were employed that included two lists of word pairs
and a cued-recall test. Repeated pairs appeared in both lists (A-B, A-B), control
pairs appeared in List 2 only (A-B, C-D), and changed pairs appeared with the
same cue in both lists but with different responses (A-B, A-D). The critical
manipulation was whether pairs were tested or restudied in an interpolated phase
that occurred between Lists 1 and 2. On a final cued-recall test, participants
recalled List 2 responses and then indicated when they recollected that responses
had earlier changed between lists. The change recollection measure indexed the
extent to which competing responses were integrated during List 2. Change was
recollected more often for tested than for restudied pairs. Proactive
facilitation was obtained in cued recall when change was recollected, whereas
proactive interference was obtained when change was not recollected. These
results provide evidence that testing counteracted proactive interference in part
by making List 1 responses more accessible during List 2, thus promoting
integration and increasing later recollection of change. These results have
theoretical implications because they show that testing can counteract proactive
interference by integrating or segregating competing information.
PMID- 25120242
TI - Getting completely turned around: how disorientation impacts subjective straight
ahead.
AB - In manipulating a pointer to indicate subjective straight ahead (SSA),
participants were more variable after a series of whole-body rotations in
conjunction with external sensory blockade than after external sensory blockade
alone. The variability of reported SSA did not increase consequent to a temporal
delay matched to the time taken by the rotation procedure. These results suggest
that an observer's egocentric reference frame is more complex and less stable
than has previously been thought.
PMID- 25120239
TI - Protease-activated receptor 4: a critical participator in inflammatory response.
AB - Protease-activated receptors (PARs) are G protein-coupled receptors of which four
members PAR1, PAR2, PAR3, and PAR4 have been identified, characterized by a
typical mechanism of activation involving various related proteases. The amino
terminal sequence of PARs is cleaved by a broad array of proteases, leading to
specific proteolytic cleavage which forms endogenous tethered ligands to induce
agonist-biased PAR activation. The biological effect of PARs activated by
coagulation proteases to regulate hemostasis and thrombosis plays an enormous
role in the cardiovascular system, while PAR4 can also be activated by trypsin,
cathepsin G, the activated factor X of the coagulation cascade, and trypsin IV.
Irrespective of its role in thrombin-induced platelet aggregation, PAR4
activation is believed to be involved in inflammatory lesions, as show by
investigations that have unmasked the effects of PAR4 on neutrophil recruitment,
the regulation of edema, and plasma extravasation. This review summarizes the
roles of PAR4 in coagulation and other extracellular protease pathways, which
activate PAR4 to participate in normal regulation and disease.
PMID- 25120243
TI - Revision laryngeal framework surgery performed by directly pulling the lateral
cricoarytenoid muscle.
AB - BACKGROUND: Revision laryngeal framework surgery is usually performed for
medialisation laryngoplasty failure, rather than for failure after arytenoid
adduction. We describe a new method for revision arytenoid adduction surgery,
performed by directly pulling the lateral cricoarytenoid muscle ('lateral
cricoarytenoid muscle pull surgery'). METHODS: We describe a case of revision
laryngeal framework surgery, present a literature review and describe the
advantages of lateral cricoarytenoid muscle pull surgery over the original method
of arytenoid adduction using a posterior approach. RESULTS: Medialisation
laryngoplasty combined with arytenoid adduction was performed following
unilateral vocal fold paralysis from mediastinal surgery, resulting in severe
glottic insufficiency. The patient's voice improved after the initial surgery,
but had deteriorated 18 months later. Revision surgery was performed using
lateral cricoarytenoid muscle pull surgery, and her voice recovered normally in
terms of perceptual impression. The post-operative course was uneventful for 10
months following revision surgery. CONCLUSION: To our knowledge, this is the
first case of revision arytenoid adduction performed using a lateral
cricoarytenoid muscle pull approach. Lateral cricoarytenoid muscle pull surgery
should therefore be considered as a new fenestration approach for arytenoid
adduction.
PMID- 25120244
TI - Dual-phase (99m)Tc-MIBI scintigraphy with delayed neck and thorax SPECT/CT and
bone scintigraphy in patients with primary hyperparathyroidism: correlation with
clinical or pathological variables.
AB - PURPOSE: The purpose of this study was to assess the relationship between (99m)Tc
MIBI and (99m)Tc-MDP bone scintigraphy and clinical or pathological variables,
including preoperative serum PTH levels and tumor diameter, in patients with
newly diagnosed PHPT. METHODS: Dual-phase (99m)Tc-MIBI planar scintigraphy was
performed in 244 patients with PHPT. Of these patients, 155 underwent (99m)Tc-MDP
bone scintigraphy to detect bone changes before parathyroidectomy. Factors
influencing (99m)Tc-MIBI scintigraphy and (99m)Tc-MDP bone scintigraphy detection
rate were assessed using univariate and multivariate logistic regression
analysis; optimal cutoff values for predicting positive (99m)Tc-MIBI and (99m)Tc
MDP bone scintigraphy were evaluated using ROC analysis. RESULTS: Among 244
patients, 174 (71.31 %) patients with 181 foci had a positive (99m)Tc-MIBI planar
scintigraphy; delayed neck and thorax SPECT/CT could identify and locate the
(99m)Tc-MIBI lesions but could not find more lesions than planar scintigraphy. 70
(28.69 %) patients had a negative (99m)Tc-MIBI planar scintigraphy. Tumor
diameter, serum PTH level and symptoms were statistically significant predictive
factors in predicting positive (9m)Tc-MIBI scintigraphy both univariate and
multivariate logistic regression analyses. The optimal thresholds for tumor
diameter and serum PTH by ROC analysis were 1.03 cm and 127.60 ng/L,
respectively. Among 155 patients with bone scintigraphy, (99m)Tc-MDP bone
scintigraphy showed positive finding in 80 (51.61 %) patients and negative
finding in 75 patients. Univariate logistic regression analysis showed that
patient age, sex, tumor diameter and PTH level (>=150 ng/L) were statistically
significant in predicting positive (99m)Tc-MDP bone scintigraphy. Multivariate
logistic regression analysis showed both tumor diameter and PTH >= 150 ng/L were
statistically significant in predicting positive (99m)Tc-MDP bone scintigraphy.
The optimal thresholds for tumor diameter and serum PTH by ROC analysis were 1.96
cm and 163.85 ng/L, respectively. CONCLUSIONS: The utility of delayed neck and
thorax SPECT/CT over dual-phase (99m)Tc-MIBI planar scintigraphy is that it can
identify and locate a parathyroid tumor in about more than 70 % of patients in
PHPT and provide the assistance for surgical planning. These studies also suggest
that (99m)Tc-MIBI scintigraphy and (99m)Tc-MDP bone scintigraphy are closely
correlated with tumor diameter and PTH; which may show negative results when
tumor diameter is small and serum PTH level is low.
PMID- 25120245
TI - The role of FDG-PET/CT in differentiated thyroid cancer patients with negative
iodine-131 whole-body scan and elevated anti-Tg level.
AB - AIM: In the follow-up of differentiated thyroid cancer (DTC) after a successful
total-near total thyroidectomy and I-131 ablation therapy, anti-thyroglobulin
antibodies (anti-Tg) may be persistently or progressively increased in the
patients with an undetectable serum thyroglobulin (Tg) level. In these cases,
further investigation was performed to search for recurrence/metastases. The aim
of our study was clarifying the role of FDG-PET/CT in detecting
recurrence/metastasis in patients with DTC with negative serum Tg and elevated
anti-Tg level. MATERIALS AND METHODS: A total of 40 patients (32 female, 8 male;
mean age: 43.15 years (22-65); mean age at diagnosis: 39.08 (16-64)) with DTC who
had undetectable serum Tg and elevated anti-Tg level after a successful initial
therapy were included in the study. All of the patients had serum anti-Tg of >40
IU/ml and underwent FDG-PET/CT to search for recurrence/metastasis. RESULTS:
Twenty patients (50 %) had recurrence/metastasis on FDG-PET/CT while the other 20
had no pathologic findings. Of the 20 patients who had positive FDG-PET/CT, 12
had a histopathological final diagnosis of which 11 were true positive (TP) and 1
was false positive (FP). On the other hand, 16 of the 40 patients had a
histopathological final diagnosis of which 11/16 had TP, 1/16 FP, 3/16 false
negative (FN) and 1/16 true negative (TN) findings by PET/CT. The final diagnosis
was made by clinical follow-up in the remaining 24 patients. Of these, 8 patients
were PET positive, and in 1 (12.5 %) of 8 patients a decrease in serum anti-Tg
level, in 2 (25 %) patients a saw-toothed pattern and in 5 (62.5 %) a progressive
increase in the serum anti-Tg level were noted during the follow-up. Of the 16 of
24 patients who were diagnosed by clinical follow-up, in 8 a (50 %) decrease in
serum anti-Tg level, in 6 (37.5 %) a saw-toothed pattern, and in 2 (12.5 %) a
progressively increased anti-Tg level was seen. Of the 40 patients, 14 (35 %) had
a diagnosis of recurrence/metastasis finally, with PET/CT detecting 11 (78.6 %)
of them. CONCLUSION: The value of a persistently or progressively increased serum
anti-Tg level in the follow-up of DTC in the prediction of recurrence/metastasis
is controversial. However, it is reported that FDG-PET can be useful in the
detection of recurrence/metastasis. We conclude from the available data that
PET/CT can be effectively used in the detection of recurrence/metastasis in the
follow-up of patients with DTC and negative serum Tg and a
persistently/progressively increased anti-Tg level. Besides, one half of the
patients were FDG negative, meaning that further studies are needed to assess the
prognostic-clinical value of PET negativity.
PMID- 25120246
TI - A laparoscopic gastrectomy approach decreases the incidence and severity of
emergence agitation after sevoflurane anesthesia.
AB - PURPOSE: Compared to open gastrectomy (OG), laparoscopic gastrectomy (LG) has
improved short-term outcomes and equivalent oncological outcomes. In this study,
a potential short-term advantage of LG over OG, reduced risk of emergence
agitation, was evaluated. METHODS: This retrospective study compared LG versus OG
with respect to emergence agitation in 400 adult patients who underwent
sevoflurane anesthesia. In all cases, a serial Richmond Agitation-Sedation Scale
(RASS) assessment was performed in the postanesthesia care unit (PACU). Patients
with a RASS score >=+1 at any time were considered to have emergence agitation.
Severe agitation was defined as a RASS score of +3 or +4. RESULTS: This study
included 214 OG group subjects and 186 LG group subjects in the analysis. The
overall incidence of emergence agitation was significantly lower in the LG group
than the OG group (23.7 vs. 43.5 %, p < 0.001). The LG group had a significantly
lower incidence of severe agitation than the OG group (1.1 vs. 4.7 %, p = 0.035).
Multivariate logistic regression analysis demonstrated that the type of surgery
(OG vs. LG), as well as current smoking, total dose of rescue opioids used in the
PACU, and maximum pain score in the PACU, were independent risk factors for
emergence agitation (odds ratio, 1.984; 95 % confidence interval, 1.249-3.153; p
= 0.004). Patients with emergence agitation had significantly increased PACU
stays (p = 0.024). CONCLUSIONS: Compared to an open approach, a laparoscopic
gastrectomy approach can provide the short-term benefit of decreased emergence
agitation.
PMID- 25120247
TI - Risk factors for weight loss among patients surviving 5 years after esophageal
cancer surgery.
AB - BACKGROUND: This study aimed to identify factors influencing postoperative weight
loss >=15 % in long-term survivors after esophageal cancer surgery. METHODS: A
population-based study was conducted in Sweden between 2001 and 2005, with
regular follow-up for 5 years. Current weight, weight at operation, and average
weight were assessed and dichotomized as weight loss of >=15 %. Logistic
regression estimated relative risks of weight loss between pre- and 5 years
postoperatively, expressed as odds ratios (ORs) with 95 % confidence intervals
(CIs). Statistically significant differences in nutritional symptoms between
weight loss groups were analyzed using linear regression models to likewise test
as risk factors. Body mass index (BMI) at operation (< or >=25), sex, and
preoperative weight loss (< or >=10 %) were tested as risk factors. Nutritional
symptoms were selected from the European Organisation for Research and Treatment
of Cancer (EORTC) QLQ-C30 and QLQ-OES18, including fatigue, nausea and vomiting,
dyspnoea, appetite loss, diarrhea, and dysphagia, eating difficulties, reflux and
pain. RESULTS: A total of 117 patients were included. Patients with preoperative
BMI >=25 were at a threefold increased risk (OR 3.2; 95 % CI 1.4-7.3) for
postoperative weight loss of >=15 % 5 years after operation. Moreover, eating
difficulties, pain, fatigue, nausea and vomiting, and appetite loss were
clinically relevant and statistically significantly worse symptoms experienced
among those with a weight loss of >=15 % (all at p < 0.05). CONCLUSIONS:
Overweight at the time of operation is associated with postoperative weight loss
from a long-term perspective. Several nutritional symptoms are associated with
weight loss of >15 % 5 years postoperatively.
PMID- 25120248
TI - Low infiltration of peritumoral regulatory T cells predicts worse outcome
following resection of colorectal liver metastases.
AB - BACKGROUND: The tumor-infiltrating lymphocyte (TIL) count in several types of
cancer, including colorectal cancer and colorectal liver metastases (CRLM),
reportedly predicts survival following resection; however, the prognostic
significance of the TIL counts remains controversial. METHODS: In total, 162
patients who underwent potentially curative resection for CRLM from 1992 to 2010
were immunohistochemically analyzed retrospectively. CD4, CD8, and FoxP3 were
examined as markers for helper T cells, cytotoxic T cells, and regulatory T cells
(Tregs), respectively. The correlation between patients' TIL composition and long
term outcome was investigated. RESULTS: The median follow-up time was 46.6 months
for all patients and 46.8 months for survivors. Cancer-specific survival (CSS) at
1, 3, and 5 years was 93.2, 65.6, and 51.0 %, respectively. The 5-year disease
free survival and CSS among patients with high infiltration of peritumoral Tregs
was 44.2 and 74.8 %, respectively, while those of patients with low infiltration
of peritumoral Tregs was 18.9 and 40.3 %, respectively (p < 0.01 for both).
Multivariate analyses indicated that synchronous liver metastases,
hypoalbuminemia, and low peritumoral Treg infiltration were significant
predictors of unfavorable CSS. CONCLUSIONS: Low peritumoral Treg infiltration
proved to be a significant predictor of unfavorable CSS in patients undergoing
resection for CRLM.
PMID- 25120249
TI - Impact of distal pancreatectomy on outcomes of peritoneal surface disease treated
with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
AB - BACKGROUND: Left upper quadrant involvement by peritoneal surface disease (PSD)
may require distal pancreatectomy (DP) to obtain complete cytoreduction. Herein,
we study the impact of DP on outcomes of cytoreductive surgery and hyperthermic
intraperitoneal chemotherapy (CRS/HIPEC). METHODS: Analysis of a prospective
database of 1,019 procedures was performed. Malignancy type, performance status,
resection status, comorbidities, Clavien-graded morbidity, mortality, and overall
survival were reviewed. RESULTS: DP was a component of 63 CRS/HIPEC procedures,
of which 63.3 % had an appendiceal primary. While 30-day mortality between
patients with and without DP was no different (2.6 vs. 3.2 %; p = 0.790), 30-day
major morbidity was worse in patients receiving a DP (30.2 vs. 18.8 %; p =
0.031). Pancreatic leak rate was 20.6 %. Intensive care unit days and length of
stay were longer in DP versus non-DP patients (4.6 vs. 3.5 days, p = 0.007; and
22 vs. 14 days, p < 0.001, respectively). Thirty-day readmission was similar for
patients with and without DP (29.2 vs. 21.1 %; p = 0.205). Median survival for
low-grade appendiceal cancer (LGA) patients requiring DP was 106.9 months versus
84.3 months when DP was not required (p = 0.864). All seven LGA patients
undergoing complete cytoreduction inclusive of DP were alive at the conclusion of
the study (median follow-up 11.8 years). CONCLUSIONS: CRS/HIPEC including DP is
associated with a significant increase in postoperative morbidity but not
mortality. Survival was similar for patients with LGA whether or not DP was
performed. Thus, the need for a DP should not be considered a contraindication
for CRS/HIPEC procedures in LGA patients when complete cytoreduction can be
achieved.
PMID- 25120250
TI - Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for
recurrent or progressive diffuse malignant peritoneal mesothelioma:
clinicopathologic characteristics and survival outcome.
AB - BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive
disease for which cytoreductive surgery (CRS) and hyperthermic intraperitoneal
chemotherapy (HIPEC) have been used with remarkable survival benefits. Our aim
was to analyze the clinicopathologic characteristics and prognosis of recurrent
DMPM managed with iterative CRS and HIPEC. METHODS: A retrospective analysis of a
prospectively maintained database for all patients treated for DMPM from 1989 to
2012. RESULTS: Of 205 consecutive CRS and HIPEC procedures, 44 (21.5 %) patients
underwent an iterative procedure-22 (50.0 %) males versus 22 (50.0 %) females.
Mean age at recurrence was 51.5 years. There was no 30-day mortality following an
iterative procedure, and the grade III-V morbidity was 2.3 %. The median overall
survival of patients undergoing an iterative CRS and HIPEC was 54 months versus
77 months following an initial CRS and HIPEC (p = 0.96). Patients undergoing an
iterative surgery had a 3- and 5-year survival of 61 and 46 %, respectively,
versus 60 and 52 % following an initial CRS and HIPEC. Amongst the iterative
group, the achieved complete cytoreduction (CC) score was 15.9, 18.2, 22.7, and
43.2 % for CC0, CC1, CC2 and CC3, respectively, versus 3.1, 43.5, 28.6 and 24.8
%, respectively, following initial CRS (p = 0.000). Significant predictors of an
improved survival in multivariate analysis were an epithelioid subtype, female
sex, complete or near CC (CC0 or CC1), HIPEC regimen utilized, absence of
postoperative complication, and age at diagnosis. CONCLUSION: Iterative CRS and
HIPEC can be performed safely and appear to have benefits with this group of
patients showing an improved median survival.
PMID- 25120251
TI - Quality of life after isolated limb infusion for in-transit melanoma of the
extremity.
AB - BACKGROUND: Isolated limb infusion (ILI) has been associated with persistent
edema, numbness, pain, and functional impairment of the treated limb. However,
health-related quality of life (HRQOL) has not yet been assessed using a
validated questionnaire. METHODS: Functional Assessment of Cancer Therapy
Melanoma (FACT-M) questionnaires were collected from subjects enrolled a phase I
ILI trial with temozolomide at baseline and 2, 6 weeks, and 3 months post-ILI. Of
28 enrolled patients, 19 patients received maximum tolerated dose of temozolomide
and are included in the HRQOL analysis. Clinical and operative variables and
treatment response data also were collected. RESULTS: HRQOL scores showed a trend
of improvement from baseline through 3-months post-ILI as measured by FACT-M and
the melanoma surgery scores. There were no differences in HRQOL when patients
were stratified by disease burden, clinical toxicity level, and 3-month disease
response. Additionally, fewer patients complained of pain, numbness, and swelling
of the affected limb at 3 months post-ILI compared to baseline, and also these
symptoms were improved at the immediate postoperative visit compared with
baseline. CONCLUSIONS: Despite the known morbidity of ILI, we have demonstrated
with a validated HRQOL questionnaire that HRQOL is not adversely impacted at
therapeutic doses of temozolomide delivered intra-arterially from baseline
through 3 months posttreatment. Patient centered-outcomes should be evaluated as
a standard part of all future regional therapy trials using standardized melanoma
specific HRQOL questionnaires to more completely evaluate the utility of this
type of treatment strategy.
PMID- 25120252
TI - Peritoneal surface disease with synchronous hepatic involvement treated with
Cytoreductive Surgery (CRS) and hyperthermic intraperitoneal chemotherapy
(HIPEC).
AB - BACKGROUND: Patients with peritoneal surface disease (PSD) often present with
synchronous hepatic involvement (HI). The impact of addressing the hepatic
component during CRS/HIPEC on operative and survival outcomes is not clearly
defined. METHODS: A prospective database of 1,067 procedures was reviewed based
on primary tumor, performance status, resection status, type of liver involvement
(superficial or parenchymal) and hepatic resection, morbidity, mortality, and
overall survival. RESULTS: There were 108 (10 %) CRS/HIPEC procedures performed
with synchronous liver debulking in 99 patients with PSD from 27 (33 %)
appendiceal and 32 (39 %) colorectal primary lesions. Ninety percent of patients
underwent subsegmental hepatic resection, whereas 22 % had disease with hepatic
parenchymal involvement. Median intensive care unit (ICU) and hospital stay were
3.5 and 13.6 days, respectively. Clavien grade III/IV morbidity was similar for
patients with or without resected HI (18.9 vs. 22.5 %; p = 0.39). The 30-day
mortality rate was 6.5 and 2.8 % (p = 0.07) for patients with and without
resected HI, respectively. The median survival for all patients with low-grade
appendiceal cancer was 42.1 months with resected HI and 95.5 months without HI (p
= 0.03). Median survival for colorectal cancer patients after complete
cytoreduction was 21.2 months with HI versus 33.6 months without HI (p = 0.03).
CONCLUSIONS: Synchronous resection of limited HI does not increase the morbidity
or mortality of CRS/HIPEC procedures. The survival benefit, although still
meaningful, was less for patients with HI. Resectable low volume HI in patients
with PSD from colon and appendiceal primary lesions should not be considered a
contraindication for CRS/HIPEC procedures.
PMID- 25120253
TI - Adjuvant imatinib for GIST: the pie is shrinking.
PMID- 25120254
TI - The importance of surgical volume on outcomes in thyroid surgery revisited: old
is in again : editorial response to "what's old is new again" by Julie Ann Sosa
(doi: 10.1245/s10434-014-3850-z).
PMID- 25120255
TI - Comparison of long-term outcomes of colonic stent as "bridge to surgery" and
emergency surgery for malignant large-bowel obstruction: a meta-analysis.
AB - BACKGROUND: The short-term safety and efficacy of insertion of a self-expandable
metallic colonic stent followed by elective surgery, bridge to surgery (BTS), for
malignant large-bowel obstruction (MLBO) have been well described. However, long
term oncological outcomes are still debated. Hence, this study is conducted to
evaluate long-term outcomes of colonic stent insertion followed by surgery for
MLBO. METHODS: A comprehensive electronic literature search through May 2014 was
performed to identify studies comparing long-term outcomes between BTS and
emergency surgery for MLBO. The main outcome measures were overall survival (OS),
disease-free survival (DFS), and recurrence. A meta-analysis was performed using
random-effects models to calculate risk ratios (RRs) with 95 % confidence
intervals (95 % CIs). RESULTS: There were 11 studies that matched the criteria
for inclusion, yielding a total of 1136 patients, of whom 432 (38.0 %) underwent
BTS and 704 (62.0 %) underwent emergency surgery. In OS analyses of all patients
and patients who underwent curative resection, BTS was similar to emergency
surgery [(RR = 0.95; 95 % CI 0.75-1.21; P = 0.66) (RR = 0.96; 95 % CI 0.67-1.37;
P = 0.82), respectively]. DFS (RR = 1.06; 95 % CI 0.91-1.24; P = 0.43) and
recurrence (RR = 1.13; 95 % CI 0.82-1.54; P = 0.46) did not differ significantly
between the BTS and emergency surgery groups. CONCLUSIONS: Results of this meta
analysis on long-term as well as well-described short-term outcomes suggest that
BTS could be a promising alternative strategy for MLBO patients.
PMID- 25120256
TI - Duration of breastfeeding as a risk factor for vertebral fractures.
AB - PURPOSE: Among the risk factors for osteoporosis and fractures, gynecological
history (fertile period, parity and breastfeeding) play an important part.
Changes in calcium metabolism to enable an adequate mineral transfer to the milk
have a prominent role in bone loss during breastfeeding. Data on the influence of
breastfeeding in postmenopausal osteoporosis are inconsistent. The aim of the
present study was to identify any association between duration of breastfeeding
and vertebral fractures in postmenopausal women. METHODS: All patients underwent
the following tests: bone mineral density measurements of the lumbar spine (L1
L4) and the total and femoral neck using dual-energy X-ray absorptiometry and
antero-posterior and lateral radiography of the thoracic and lumbar spine to
identify vertebral fractures. RESULTS: The study involved 752 women with a mean
age of 64.5+/-9.3; 23% of them reported vertebral osteoporotic fractures. The
women with vertebral fractures had breastfed for longer periods (11.8+/-12.9 vs.
9.3+/-11.2months, p=0.03) and had more pregnancies (2.6+/-2.2 vs. 2.2+/-1.3,
p=0.002). Breastfeeding for more than 18months was associated with a two-fold
risk of developing vertebral fractures (OR 2.12, 95% CI 1.14-5.38, p=0.04),
particularly in those without current or past use of drugs positively affecting
bone. CONCLUSIONS: Our study showed an association between long periods of
breastfeeding and vertebral fractures, supporting a role for lengthy lactation as
a risk factor for osteoporotic fractures after menopause. Bearing in mind all the
benefits of breastfeeding, this finding suggests the importance of an adequate
calcium and vitamin D intake during pregnancy and breastfeeding, with the aid of
dietary supplements if necessary.
PMID- 25120257
TI - Heavy metal concentrations of groundwater in the east of Ergene Basin, Turkey.
AB - The aim of this research was to investigate the concentrations of the heavy
metals (copper, iron, zinc, chromium, cadmium and lead) and determine their
relationship between pH and EC in the east of Ergene Basin, Turkey. For this
purpose 18 groundwater samples were collected in May 2013. Results show that mean
concentrations of Cu, Fe, Zn, Cr, Cd and Pb were, 0.005, 0.012, 0.083, 0.016,
0.000 and 0.0006 mg L(-1) respectively, with the decreasing sequence of Zn > Cr >
Fe > Cu > Pb > Cd. No significant correlations were found among metals. Only
moderate positive correlation was determined between Pb and pH (r = 0.451; p <
0.05). All metal pollutants studied in the groundwater were below international
and national guidelines except Cr.
PMID- 25120258
TI - Early life stage (ELS) toxicity of sucralose to fathead minnows, Pimephales
promelas.
AB - Sucralose, an intense artificial sweetener, has been detected in wastewater and
surface waters at concentrations ranging from ng/L to low ug/L. Although over a
hundred studies have been conducted to evaluate the safety of sucralose for human
consumption, few studies have focused on the chronic ecotoxicological effects of
this compound in fish. As a remedy to this data gap, an early-life stage toxicity
test was conducted to assess the effects of sucralose on hatching, survival, and
growth of fathead minnows (Pimephales promelas). Hatching, survival, and growth
were unaffected by 98 mg/L of sucralose. The Lowest-Observed-Effect Concentration
(LOEC) and the No-Observed-Effect Concentration (NOEC) for fathead minnows
determined by this study are >98 and 98 mg/L, respectively. The results from this
study suggest that the concentrations of sucralose detected in the environment
are well below those required to cause adverse effects to developing aquatic
organisms.
PMID- 25120259
TI - Relationship of bifenthrin sediment concentrations to grain size and total
organic carbon in California waterbodies: implications for ecological risk.
AB - A summary analysis of data sets from six California waterbodies was conducted to
determine the relationship of bifenthrin sediment concentrations to: %
sand/gravel; % silt; % clay; % silt/clay and % total organic carbon (TOC). The
relationship of TOC to % sand/gravel, % silt, % clay, and % silt/clay was also
analyzed. Statistically significant and meaningful direct relationships were
reported between bifenthrin and % TOC, % silt, % clay and % silt/clay while a
significant and meaningful inverse relationship was reported between bifenthrin
and % sand/gravel. A significant and meaningful inverse relationship was reported
between % TOC and % sand/gravel, while a significant and meaningful direct
relationship was reported between % TOC and % silt, % clay and % silt/clay.
Significant bifenthrin sediment concentrations would not be expected in non
depositional (sand/gravel) areas which have been reported to be dominant in
various streams in California's Central Valley and are also the preferred habitat
for many benthic macroinvertebrate taxa.
PMID- 25120260
TI - Biosensor analysis of anti-citrullinated protein/peptide antibody affinity.
AB - Anti-citrullinated protein/peptide antibodies (ACPAs) are detected in rheumatoid
arthritis (RA) sera and because of their strict association with the disease are
considered marker antibodies, probably endowed with pathogenic potential.
Antibody affinity is one of the parameters affecting pathogenicity. Three
diagnostic citrullinated peptides-viral citrullinated peptide 1 (VCP1) and VCP2
derived from Epstein-Barr virus (EBV)-encoded proteins and histone citrullinated
peptide 1 (HCP1) derived from histone H4-were synthesized as tetrameric multiple
antigen peptides and immobilized on sensor chips CM5 type in a Biacore T100
instrument. Specific binding of purified antibodies from RA patients to the three
peptides was analyzed by surface plasmon resonance using two arginine-containing
sequences as controls. Employing a 1:1 binding model for affinity constant
calculation, ACPAs interacted with VCP1 and VCP2 with lower apparent affinity
(10(-6) M>KD>10(-7) M) and interacted with HCP1 with higher apparent affinity
(KD=10(-8) M). The results indicate that the binding to citrullinated peptides is
characterized by wide differences in affinity, with slower association and faster
dissociation rates in the case of antibodies to viral citrullinated peptides as
compared with antibodies specific for the histone peptide. This biosensor
analysis shows the high cross-reactivity of purified ACPAs that bind other
citrullinated peptides besides the one used for purification.
PMID- 25120263
TI - The interplay of restriction-modification systems with mobile genetic elements
and their prokaryotic hosts.
AB - The roles of restriction-modification (R-M) systems in providing immunity against
horizontal gene transfer (HGT) and in stabilizing mobile genetic elements (MGEs)
have been much debated. However, few studies have precisely addressed the
distribution of these systems in light of HGT, its mechanisms and its vectors. We
analyzed the distribution of R-M systems in 2261 prokaryote genomes and found
their frequency to be strongly dependent on the presence of MGEs, CRISPR-Cas
systems, integrons and natural transformation. Yet R-M systems are rare in
plasmids, in prophages and nearly absent from other phages. Their abundance
depends on genome size for small genomes where it relates with HGT but saturates
at two occurrences per genome. Chromosomal R-M systems might evolve under cycles
of purifying and relaxed selection, where sequence conservation depends on the
biochemical activity and complexity of the system and total gene loss is
frequent. Surprisingly, analysis of 43 pan-genomes suggests that solitary R-M
genes rarely arise from the degradation of R-M systems. Solitary genes are
transferred by large MGEs, whereas complete systems are more frequently
transferred autonomously or in small MGEs. Our results suggest means of testing
the roles for R-M systems and their associations with MGEs.
PMID- 25120266
TI - MosaicSolver: a tool for determining recombinants of viral genomes from pileup
data.
AB - Viral recombination is a key evolutionary mechanism, aiding escape from host
immunity, contributing to changes in tropism and possibly assisting transmission
across species barriers. The ability to determine whether recombination has
occurred and to locate associated specific recombination junctions is thus of
major importance in understanding emerging diseases and pathogenesis. This paper
describes a method for determining recombinant mosaics (and their proportions)
originating from two parent genomes, using high-throughput sequence data. The
method involves setting the problem geometrically and the use of appropriately
constrained quadratic programming. Recombinants of the honeybee deformed wing
virus and the Varroa destructor virus-1 are inferred to illustrate the method
from both siRNAs and reads sampling the viral genome population (cDNA library);
our results are confirmed experimentally. Matlab software (MosaicSolver) is
available.
PMID- 25120265
TI - COMET: adaptive context-based modeling for ultrafast HIV-1 subtype
identification.
AB - Viral sequence classification has wide applications in clinical, epidemiological,
structural and functional categorization studies. Most existing approaches rely
on an initial alignment step followed by classification based on phylogenetic or
statistical algorithms. Here we present an ultrafast alignment-free subtyping
tool for human immunodeficiency virus type one (HIV-1) adapted from Prediction by
Partial Matching compression. This tool, named COMET, was compared to the widely
used phylogeny-based REGA and SCUEAL tools using synthetic and clinical HIV data
sets (1,090,698 and 10,625 sequences, respectively). COMET's sensitivity and
specificity were comparable to or higher than the two other subtyping tools on
both data sets for known subtypes. COMET also excelled in detecting and
identifying new recombinant forms, a frequent feature of the HIV epidemic.
Runtime comparisons showed that COMET was almost as fast as USEARCH. This study
demonstrates the advantages of alignment-free classification of viral sequences,
which feature high rates of variation, recombination and insertions/deletions.
COMET is free to use via an online interface.
PMID- 25120264
TI - Degradation of DNA damage-independently stalled RNA polymerase II is independent
of the E3 ligase Elc1.
AB - Transcription elongation is a highly dynamic and discontinuous process, which
includes frequent pausing of RNA polymerase II (RNAPII). RNAPII complexes that
stall persistently on a gene during transcription elongation block transcription
and thus have to be removed. It has been proposed that the cellular pathway for
removal of these DNA damage-independently stalled RNAPII complexes is similar or
identical to the removal of RNAPII complexes stalled due to DNA damage. Here, we
show that-consistent with previous data-DNA damage-independent stalling causes
polyubiquitylation and proteasome-mediated degradation of Rpb1, the largest
subunit of RNAPII, using Saccharomyces cerevisiae as model system. Moreover,
recruitment of the proteasome to RNAPII and transcribed genes is increased when
transcription elongation is impaired indicating that Rpb1 degradation takes place
at the gene. Importantly, in contrast to the DNA damage-dependent pathway Rpb1
degradation of DNA damage-independently stalled RNAPII is independent of the E3
ligase Elc1. In addition, deubiquitylation of RNAPII is also independent of the
Elc1-antagonizing deubiquitylase Ubp3. Thus, the pathway for degradation of DNA
damage-independently stalled RNAPII is overlapping yet distinct from the
previously described pathway for degradation of RNAPII stalled due to DNA damage.
Taken together, we provide the first evidence that the cell discriminates between
DNA damage-dependently and -independently stalled RNAPII.
PMID- 25120268
TI - Rolling circle replication requires single-stranded DNA binding protein to avoid
termination and production of double-stranded DNA.
AB - In rolling circle replication, a circular template of DNA is replicated as a long
single-stranded DNA concatamer that spools off when a strand displacing
polymerase traverses the circular template. The current view is that this type of
replication can only produce single-stranded DNA, because the only 3'-ends
available are the ones being replicated along the circular templates. In contrast
to this view, we find that rolling circle replication in vitro generates large
amounts of double stranded DNA and that the production of single-stranded DNA
terminates after some time. These properties can be suppressed by adding single
stranded DNA-binding proteins to the reaction. We conclude that a model in which
the polymerase switches templates to the already produced single-stranded DNA,
with an exponential distribution of template switching, can explain the observed
data. From this, we also provide an estimate value of the switching rate
constant.
PMID- 25120267
TI - Multiple LacI-mediated loops revealed by Bayesian statistics and tethered
particle motion.
AB - The bacterial transcription factor LacI loops DNA by binding to two separate
locations on the DNA simultaneously. Despite being one of the best-studied model
systems for transcriptional regulation, the number and conformations of loop
structures accessible to LacI remain unclear, though the importance of multiple
coexisting loops has been implicated in interactions between LacI and other
cellular regulators of gene expression. To probe this issue, we have developed a
new analysis method for tethered particle motion, a versatile and commonly used
in vitro single-molecule technique. Our method, vbTPM, performs variational
Bayesian inference in hidden Markov models. It learns the number of distinct
states (i.e. DNA-protein conformations) directly from tethered particle motion
data with better resolution than existing methods, while easily correcting for
common experimental artifacts. Studying short (roughly 100 bp) LacI-mediated
loops, we provide evidence for three distinct loop structures, more than
previously reported in single-molecule studies. Moreover, our results confirm
that changes in LacI conformation and DNA-binding topology both contribute to the
repertoire of LacI-mediated loops formed in vitro, and provide qualitatively new
input for models of looping and transcriptional regulation. We expect vbTPM to be
broadly useful for probing complex protein-nucleic acid interactions.
PMID- 25120270
TI - Crystal structure of the catalytic core of Rad2: insights into the mechanism of
substrate binding.
AB - Rad2/XPG belongs to the flap nuclease family and is responsible for a key step of
the eukaryotic nucleotide excision DNA repair (NER) pathway. To elucidate the
mechanism of DNA binding by Rad2/XPG, we solved crystal structures of the
catalytic core of Rad2 in complex with a substrate. Rad2 utilizes three
structural modules for recognition of the double-stranded portion of DNA
substrate, particularly a Rad2-specific alpha-helix for binding the cleaved
strand. The protein does not specifically recognize the single-stranded portion
of the nucleic acid. Our data suggest that in contrast to related enzymes (FEN1
and EXO1), the Rad2 active site may be more accessible, which would create an
exit route for substrates without a free 5' end.
PMID- 25120269
TI - sPARTA: a parallelized pipeline for integrated analysis of plant miRNA and
cleaved mRNA data sets, including new miRNA target-identification software.
AB - Parallel analysis of RNA ends (PARE) is a technique utilizing high-throughput
sequencing to profile uncapped, mRNA cleavage or decay products on a genome-wide
basis. Tools currently available to validate miRNA targets using PARE data employ
only annotated genes, whereas important targets may be found in unannotated
genomic regions. To handle such cases and to scale to the growing availability of
PARE data and genomes, we developed a new tool, 'sPARTA' (small RNA-PARE target
analyzer) that utilizes a built-in, plant-focused target prediction module (aka
'miRferno'). sPARTA not only exhibits an unprecedented gain in speed but also it
shows greater predictive power by validating more targets, compared to a popular
alternative. In addition, the novel 'seed-free' mode, optimized to find targets
irrespective of complementarity in the seed-region, identifies novel intergenic
targets. To fully capitalize on the novelty and strengths of sPARTA, we developed
a web resource, 'comPARE', for plant miRNA target analysis; this facilitates the
systematic identification and analysis of miRNA-target interactions across
multiple species, integrated with visualization tools. This collation of high
throughput small RNA and PARE datasets from different genomes further facilitates
re-evaluation of existing miRNA annotations, resulting in a 'cleaner' set of
microRNAs.
PMID- 25120273
TI - Detection of AGEs as markers for carbohydrate metabolism and protein
denaturation.
AB - Approximately 100 years have passed since the Maillard reaction was first
reported in the field of food chemistry as a condensation reaction between
reducing sugars and amino acids. This reaction is thought to progress slowly
primarily from glucose with proteins in vivo. An early-stage product, called the
"Amadori product", is converted into advanced glycation end products. Those
accumulate in the body in accordance with age, with such accumulation being
enhanced by lifestyle-related diseases that result in the denaturation of
proteins. Recent studies have demonstrated that intermediate carbonyls are
generated by several pathways, and rapidly generate many glycation products.
However, accurate quantification of glycation products in vivo is difficult due
to instability and differences in physicochemical properties. In this connection,
little is known about the relationship between the structure of glycation
products and pathology. Furthermore, the interaction between proteins modified by
glycation and receptors for advanced glycation end products is also known to
induce the production of several inflammatory cytokines. Therefore, those
inhibitors have been developed over the world to prevent lifestyle-related
diseases. In this review, we describe the process of protein denaturation induced
by glycation and discuss the possibility of using the process as a marker of age
related diseases.
PMID- 25120272
TI - Syntheses and characterizations of the in vivo replicative bypass and mutagenic
properties of the minor-groove O2-alkylthymidine lesions.
AB - Endogenous metabolism, environmental exposure, and treatment with some
chemotherapeutic agents can all give rise to DNA alkylation, which can occur on
the phosphate backbone as well as the ring nitrogen or exocyclic nitrogen and
oxygen atoms of nucleobases. Previous studies showed that the minor-groove O(2)
alkylated thymidine (O(2)-alkyldT) lesions are poorly repaired and persist in
mammalian tissues. In the present study, we synthesized oligodeoxyribonucleotides
harboring seven O(2)-alkyldT lesions, with the alkyl group being a Me, Et, nPr,
iPr, nBu, iBu or sBu, at a defined site and examined the impact of these lesions
on DNA replication in Escherichia coli cells. Our results demonstrated that the
replication bypass efficiencies of the O(2)-alkyldT lesions decreased with the
chain length of the alkyl group, and these lesions directed promiscuous
nucleotide misincorporation in E. coli cells. We also found that deficiency in
Pol V, but not Pol II or Pol IV, led to a marked drop in bypass efficiencies for
most O(2)-alkyldT lesions. We further showed that both Pol IV and Pol V were
essential for the misincorporation of dCMP opposite these minor-groove DNA
lesions, whereas only Pol V was indispensable for the T->A transversion
introduced by these lesions. Depletion of Pol II, however, did not lead to any
detectable alterations in mutation frequencies for any of the O(2)-alkyldT
lesions. Thus, our study provided important new knowledge about the cytotoxic and
mutagenic properties of the O(2)-alkyldT lesions and revealed the roles of the
SOS-induced DNA polymerases in bypassing these lesions in E. coli cells.
PMID- 25120274
TI - Brazilian green propolis improves immune function in aged mice.
AB - Aging weakened innate and adaptive immunity both quantitatively and
qualitatively. Some components in propolis could stimulate immune function in
young animals or cultured immune cells in vitro. Few studies had been carried out
in the aged. The present study was to evaluate the effects of Brazilian green
propolis supplementation on the immunological parameters in aged mice. Eighty
Kunming mice, aged 15-18 months, were randomly assigned to the control and three
experimental groups supplemented with different doses (83.3, 157.4 and 352.9
mg/kg.bw respectively) of Brazilian green propolis. The experiment lasted for 4
weeks. Contents of total polyphenol, flavonoid, cinnamic acid and artepillin-C in
Brazilian green propolis were analyzed. Splenic NK cytotoxic, T lymphocyte
proliferation and antibody generation cells, as well as the phagocytosis of
peritoneal macrophages, ear swelling, and serum contents of IgG, IgM, hemolysin
and cytokines were measured. After 4 weeks of treatment, the phagocytosis of
peritoneal macrophages was enhanced in 157.4 mg/kg and 352.9 mg/kg groups. Ear
swelling increased in all propolis treatmented groups. Antibodies specific to
sheep erythrocytes were higher in the groups receiving 157.4 and 352.9 mg/kg.bw
than that of control group. IgG level dramatically increased in the groups
receiving 83.3 and 157.4 mg/kg.bw in comparison to the control group. These
results indicate that administration of Brazilian green propolis have a positive
effect on innate and adaptive immunity in aged mice.
PMID- 25120271
TI - The bone-specific Runx2-P1 promoter displays conserved three-dimensional
chromatin structure with the syntenic Supt3h promoter.
AB - Three-dimensional organization of chromatin is fundamental for transcriptional
regulation. Tissue-specific transcriptional programs are orchestrated by
transcription factors and epigenetic regulators. The RUNX2 transcription factor
is required for differentiation of precursor cells into mature osteoblasts.
Although organization and control of the bone-specific Runx2-P1 promoter have
been studied extensively, long-range regulation has not been explored. In this
study, we investigated higher-order organization of the Runx2-P1 promoter during
osteoblast differentiation. Mining the ENCODE database revealed interactions
between Runx2-P1 and Supt3h promoters in several non-mesenchymal human cell
lines. Supt3h is a ubiquitously expressed gene located within the first intron of
Runx2. These two genes show shared synteny across species from humans to sponges.
Chromosome conformation capture analysis in the murine pre-osteoblastic MC3T3-E1
cell line revealed increased contact frequency between Runx2-P1 and Supt3h
promoters during differentiation. This increase was accompanied by enhanced
DNaseI hypersensitivity along with RUNX2 and CTCF binding at the Supt3h promoter.
Furthermore, interplasmid-3C and luciferase reporter assays showed that the
Supt3h promoter can modulate Runx2-P1 activity via direct association. Taken
together, our data demonstrate physical proximity between Runx2-P1 and Supt3h
promoters, consistent with their syntenic nature. Importantly, we identify the
Supt3h promoter as a potential regulator of the bone-specific Runx2-P1 promoter.
PMID- 25120275
TI - Tempol intake improves inflammatory status in aged mice.
AB - Oxidative stress is associated with both healthy aging and age-related disease
states. In connection with oxidative stress, immunity is also a major component
as a result of the chronic, low-grade inflammation associated with the
development of tissue aging. Here we show that long-term treatment with the
antioxidant tempol extends life-span in mice. Tempol-treated mice exhibited a
reduction in mortality at 20 months. Tempol drinking did not have any effect on
body weight, amount of visceral adipose tissue, or plasma biochemical parameters
in aged mice. Body temperature of aged control mice (which drank only water) was
significantly lower than young mice, but this reduction of body temperature was
partially restored in aged mice which drank tempol. Plasma thiobarbituric acid
reactive substances and C-reactive protein were significantly increased in the
control aged mice compared with young mice, but levels of both were normalized by
tempol drinking. One of the endogenous antioxidants, ascorbic acid, was
significantly increased in the plasma of mice which consumed tempol. The
proportion of CD4 lymphocytes in the blood of aged tempol-treated mice was
partially increased in comparison to aged control mice. These results suggest
that the reduction of mortality by tempol is due to amelioration of chronic
inflammation and improved function of the immune system through antioxidant
effects.
PMID- 25120276
TI - Acetaldehyde is an oxidative stressor for gastric epithelial cells.
AB - Alcohol drinking and smoking contain the risk of a carcinogenesis. Acetaldehyde
is content in cigarette smoke and an ethanol metabolite. However the clear
evidence for reactive oxygen species (ROS) generation by acetaldehyde in gastric
cells in vitro is none. In this study, we elucidated acetaldehyde is an oxidative
stress inducer on rat gastric epithelial cells by electron paramagnetic resonance
measurement in living cells. We also confirmed whether acetaldehyde-induced
cellular ROS was derived from mitochondria or not. The results of cellular ROS
determination showed that an increment of cellular ROS was shown for 15 min in
living cells from exposing 0.1% (v/v) acetaldehyde. Lipid peroxidation in
cellular membrane also induced by 0.1% ethanol and the tendency is same in the
results of cellular ROS determination. JC-1 stained showed the decrement of
mitochondrial membrane potential. These results indicated that acetaldehyde is
not merely a necrotizing factor for gastric epithelial cells, but also an
oxidative stress inducer via injured mitochondria.
PMID- 25120277
TI - Citrulline increases cholesterol efflux from macrophages in vitro and ex vivo via
ATP-binding cassette transporters.
AB - Reverse cholesterol transport (RCT) is a mechanism critical to the anti
atherogenic property of HDL. Although citrulline contributes to the amelioration
of atherosclerosis via endothelial nitric oxide production, it remains unclear
whether it affects RCT. This study was undertaken to clarify the effects of
citrulline on expressions of specific transporters such as ATP binding cassette
transporters (ABC)A1 and ABCG1, and the cholesterol efflux from macrophages to
apolipoprotein (apo) A-I or HDL in vitro and ex vivo. Citrulline increased ABCA1
and ABCG1 mRNA and protein levels in THP-1 macrophages, translating into enhanced
apoA-I- and HDL-mediated cholesterol efflux. In the human crossover study, 8
healthy male volunteers (age 30-49 years) consumed either 3.2 g/day citrulline or
placebo for 1 week. Citrulline consumption brought about significant increases in
plasma levels of citrulline and arginine. Supporting the in vitro data, monocyte
derived macrophages (MDM) differentiated under autologous post-citrulline sera
demonstrated enhancement of both apoA-I- and HDL-mediated cholesterol efflux
through increased ABCA1 and ABCG1 expressions, compared to MDM differentiated
under pre-citrulline sera. However, the placebo did not modulate these
parameters. Therefore, in addition to improving endothelium function, citrulline
might have an anti-atherogenic property by increasing RCT of HDL.
PMID- 25120278
TI - Maternal protein restriction induces alterations in hepatic tumor necrosis factor
alpha/CYP7A1 signaling and disorders regulation of cholesterol metabolism in the
adult rat offspring.
AB - It is well recognized that adverse events in utero impair fetal development and
lead to the development of obesity and metabolic syndrome in adulthood. To
investigate the mechanisms linking impaired fetal growth to increased
cholesterol, an important clinical risk factor characterizing the metabolic
syndrome and cardiovascular disease, we examined the impact of maternal
undernutrition on tumor necrosis factor-alpha (TNF-alpha)/c-jun N-terminal kinase
(JNK) signaling pathway and the cholesterol 7alpha-hydroxylase (CYP7A1)
expression in the livers of the offspring with a protein restriction model. The
male offspring with intrauterine growth restriction (IUGR) caused by the
isocaloric low-protein diet showed decreased liver weight at birth and augmented
circulation and hepatic cholesterol levels at 40 weeks of age. Maternal
undernutrition significantly upregulated cytokine TNF-alpha expression and JNK
phospholytion levels in the livers from fetal age to adulthood. Elevated JNK
phospholytion could be linked to downregulated hepatocyte nuclear factor-4alpha
and CYP7A1 expression, subsequently led to higher hepatic cholesterol. This work
demonstrated that intrauterine malnutrition-induced IUGR might result in
intrinsic disorder in hepatic TNF-alpha/CYP7A1 signaling, and contribute to the
development of hypercholesterolemia in later life.
PMID- 25120279
TI - Consumption of strawberries on a daily basis increases the non-urate 2,2-diphenyl
1-picryl-hydrazyl (DPPH) radical scavenging activity of fasting plasma in healthy
subjects.
AB - Strawberries contain anthocyanins and ellagitanins which have antioxidant
properties. We determined whether the consumption of strawberries increase the
plasma antioxidant activity measured as the ability to decompose 2,2-diphenyl-1
picrylhydrazyl radical (DPPH) in healthy subjects. The study involved 10
volunteers (age 41 +/- 6 years, body weight 74.4 +/- 12.7 kg) that consumed 500 g
of strawberries daily for 9 days and 7 matched controls. Fasting plasma and spot
morning urine samples were collected at baseline, during fruit consumption and
after a 6 day wash-out period. DPPH decomposition was measured in both
deproteinized native plasma specimens and pretreated with uricase (non-urate
plasma). Twelve phenolics were determined with HPLC. Strawberries had no effect
on the antioxidant activity of native plasma and circulating phenolics. Non-urate
plasma DPPH decomposition increased from 5.7 +/- 0.6% to 6.6 +/- 0.6%, 6.5 +/-
1.0% and 6.3 +/- 1.4% after 3, 6 and 9 days of supplementation, respectively. The
wash-out period reversed this activity back to 5.7 +/- 0.8% (p<0.01). Control
subjects did not reveal any changes of plasma antioxidant activity. Significant
increase in urinary urolithin A and 4-hydroxyhippuric (by 8.7- and 5.9-times
after 6 days of supplementation with fruits) was noted. Strawberry consumption
can increase the non-urate plasma antioxidant activity which, in turn, may
decrease the risk of systemic oxidants overactivity.
PMID- 25120280
TI - The inhibitory effect of heat treatment against epithelial-mesenchymal transition
(EMT) in human pancreatic adenocarcinoma cell lines.
AB - Epithelial-mesenchymal transition (EMT) plays a crucial role in cancer
metastasis. In this study, we evaluated the effect of heat treatment on tumor
growth factor-beta1 (TGF-beta1)-induced EMT in pancreatic cancer cells and tried
to ascertain the mechanism related to any observed effects. Human pancreatic
cancer cell lines (BxPC-3, PANC-1 and MIAPaCa-2) were stimulated by TGF-beta1,
and evaluated for morphological changes using immunofluorescence and EMT-related
factors (i.e., E-cadherin, Vimentin, Snail or ZEB-1) using RT-PCR. To examine the
effect of heat on EMT, the cancer cells were heat-treated at 43 degrees C for 1 h
then stimulated with TGF-beta1. We then evaluated whether or not heat treatment
changed the expression of EMT-related factors and cell migration and also whether
Smad activation was inhibited in TGF-beta signaling. After being treated with TGF
beta1, pancreatic cancer cells resulted in EMT and cell migration was enhanced.
Heat treatment inhibited TGF-beta1-induced changes in morphology, inhibited the
expression of EMT-related factors, and attenuated TGF-beta1-induced migration in
pancreatic cancer cells. Additionally, we observed that heat treatment blocked
TGF-beta1-induced phosphorylation of Smad2 in PANC-1 cells. Our results suggest
that heat treatment can suppress TGF-beta1-induced EMT and opens the possibility
of a new therapeutic use of hyperthermia as a potential treatment for cancer
metastasis.
PMID- 25120281
TI - Estimate of dietary phosphorus intake using 24-h urine collection.
AB - Increases in serum phosphorus levels and dietary phosphorus intake induces
vascular calcification, arterial sclerosis and cardiovascular diseases. Limiting
phosphorus intake is advisable, however, no assessment methods are capable of
estimating dietary phosphorus intake. We hypothesized that urinary phosphorus
excretion can be translated into estimation of dietary phosphorus intake, and we
evaluated whether a 24-h urine collection method could estimate dietary
phosphorus intake. Thirty two healthy subjects were recruited for this study.
Subjects collected urine samples over 24 h and weighed dietary records. We
calculated dietary protein intake and phosphorus intake from dietary records and
urine collection, and investigated associations between the two methods in
estimating protein and phosphorus intake. Significant positive correlations were
observed between dietary records and UC for protein and phosphorus intake. The
average intakes determined from dietary records were significantly higher than
from urine collection for both protein and phosphorus. There was a significant
positive correlation between both the phosphorus and protein difference in
dietary records and urine collection. The phosphorus-protein ratio in urine
collection was significantly higher than in dietary records. Our data indicated
that the 24-h urine collection method can estimate the amount of dietary
phosphorus intake, and the results were superior to estimation by weighed dietary
record.
PMID- 25120282
TI - Mitochondrial reactive oxygen species accelerate the expression of heme carrier
protein 1 and enhance photodynamic cancer therapy effect.
AB - Photodynamic therapy using hematoporphyrin and its derivatives is clinically
useful for cancer treatments. It has been reported that cancer cells incorporate
hematoporphyrin and its derivatives via heme carrier protein 1, which is a proton
coupled folate transporter. However, the mechanism of this protein expression has
not been elucidated. In general, the concentration of reactive oxygen species in
cancer cells is higher than that in normal cells. We previously reported that
reactive oxygen species from mitochondria involved in the expression of peptide
transporter 1 and accelerate the uptake of 5-aminolevulinic acid, which is a
precursor of protoporphyrin IX. We suggested mitochondrial reactive oxygen
species also regulated the expression of heme carrier protein 1. In this study,
we used a rat gastric mucosal cell line RGM1 and its cancer-like mutated cell
line RGK1. We clarified the expression of heme carrier protein 1 increased in
cancer cells and it decreased in manganese superoxide dismutase expressed cancer
cells. In addition, the uptake level of hematoporphyrin and photodynamic
therapeutic effect were also decreased in manganese superoxide dismutase
expressed cancer cells in comparison with cancer cells. Thus, we concluded that
mitochondrial reactive oxygen species regulated heme carrier protein 1 expression
and photodynamic therapeutic effect.
PMID- 25120283
TI - Improvement in medical students' communication and interpersonal skills as
evaluated by patient satisfaction questionnaire after curriculum reform.
AB - Fifteen years of undergraduate medical education curriculum reform at Saga
Medical School was evaluated by measuring medical students' communication and
interpersonal skills with a patient satisfaction questionnaire developed by the
American Board of Internal Medicine. A multiphase cross-sectional study was
conducted at the General Medicine Clinic of Saga Medical School Hospital in phase
I (1998-1999), phase II (2001-2002), and phase III (2009-2010). A total of 1,963
patient ratings for 437 medical students' performance was analyzed. The average
scores of phases II and III were significantly higher than for phase I. The
average score of female students showed a significant difference between phases I
and II, but no difference between phases II and III. The average score of male
students showed no difference between phases I and II, but significant difference
between phases II and III. The phase II curriculum introduced basic clinical
skills and examination and improved female students' performance. The phase III
curriculum was effective for male students because it emphasized the clinical
skill program more and introduced problem-based learning. Curriculum reform at
Saga Medical School is considered to have made good progress in improving
students' clinical competence and patient-centered attitudes.
PMID- 25120284
TI - Diagnostic utility of broad range bacterial 16S rRNA gene PCR with degradation of
human and free bacterial DNA in bloodstream infection is more sensitive than an
in-house developed PCR without degradation of human and free bacterial DNA.
AB - We compared a commercial broad range 16S rRNA gene PCR assay (SepsiTest) to an in
house developed assay (IHP). We assessed whether CD64 index, a biomarker of
bacterial infection, can be used to exclude patients with a low probability of
systemic bacterial infection. From January to March 2010, 23 patients with
suspected sepsis were enrolled. CD64 index, procalcitonin, and C-reactive protein
were measured on admission. Broad range 16S rRNA gene PCR was performed from
whole blood (SepsiTest) or blood plasma (IHP) and compared to blood culture
results. Blood samples spiked with Staphylococcus aureus were used to assess
sensitivity of the molecular assays in vitro. CD64 index was lower in patients
where possible sepsis was excluded than in patients with microbiologically
confirmed sepsis (P = 0.004). SepsiTest identified more relevant pathogens than
blood cultures (P = 0.008); in three patients (13%) results from blood culture
and SepsiTest were congruent, whereas in four cases (17.4%) relevant pathogens
were detected by SepsiTest only. In vitro spiking experiments suggested equal
sensitivity of SepsiTest and IHP. A diagnostic algorithm using CD64 index as a
decision maker to perform SepsiTest shows improved detection of pathogens in
patients with suspected blood stream infection and may enable earlier targeted
antibiotic therapy.
PMID- 25120285
TI - Induction of IL-12 production in human peripheral monocytes by Trypanosoma cruzi
Is mediated by glycosylphosphatidylinositol-anchored mucin-like glycoproteins and
potentiated by IFN- gamma and CD40-CD40L interactions.
AB - Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is
characterized by immunopathology driven by IFN-gamma secreting Th1-like T cells.
T. cruzi has a thick coat of mucin-like glycoproteins covering its surface, which
plays an important role in parasite invasion and host immunomodulation. It has
been extensively described that T. cruzi or its products-like GPI anchors
isolated from GPI-anchored mucins from the trypomastigote life cycle stage (tGPI
mucins)-are potent inducers of proinflammatory responses (i.e., cytokines and NO
production) by IFN-gamma primed murine macrophages. However, little is known
about whether T. cruzi or GPI-mucins exert a similar action in human cells. We
therefore decided to further investigate the in vitro cytokine production profile
from human mononuclear cells from uninfected donors exposed to T. cruzi as well
as tGPI-mucins. We observed that both living T. cruzi trypomastigotes and tGPI
mucins are potent inducers of IL-12 by human peripheral blood monocytes and this
effect depends on CD40-CD40L interaction and IFN-gamma. Our findings suggest that
the polarized T1-type cytokine profile seen in T. cruzi infected patients might
be a long-term effect of IL-12 production induced by lifelong exposure to T.
cruzi tGPI-mucins.
PMID- 25120289
TI - Cost of treating diabetic kidney disease.
PMID- 25120286
TI - Can the TLR-4-mediated signaling pathway be "a key inflammatory promoter for
sporadic TAA"?
AB - Thoracic aorta shows with advancing age various changes and a progressive
deterioration in structure and function. As a result, vascular remodeling (VR)
and medial degeneration (MD) occur as pathological entities responsible
principally for the sporadic TAA onset. Little is known about their genetic,
molecular, and cellular mechanisms. Recent evidence is proposing the strong role
of a chronic immune/inflammatory process in their evocation and progression.
Thus, we evaluated the potential role of Toll like receptor- (TLR-) 4-mediated
signaling pathway and its polymorphisms in sporadic TAA. Genetic,
immunohistochemical, and biochemical analyses were assessed. Interestingly, the
rs4986790 TLR4 polymorphism confers a higher susceptibility for sporadic TAA (OR
= 14.4, P = 0.0008) and it represents, together with rs1799752 ACE, rs3918242 MMP
9, and rs2285053 MMP-2 SNPs, an independent sporadic TAA risk factor. In
consistency with these data, a significant association was observed between their
combined risk genotype and sporadic TAA. Cases bearing this risk genotype showed
higher systemic inflammatory mediator levels, significant inflammatory/immune
infiltrate, a typical MD phenotype, lower telomere length, and positive
correlations with histopatological abnormalities, hypertension, smoking, and
ageing. Thus, TLR4 pathway should seem to have a key role in sporadic TAA. It
might represent a potential useful tool for preventing and monitoring sporadic
TAA and developing personalized treatments.
PMID- 25120288
TI - Cholesterol oxidase binds TLR2 and modulates functional responses of human
macrophages.
AB - Cholesterol oxidase (ChoD) is considered to be an important virulence factor for
Mycobacterium tuberculosis (Mtb), but its influence on macrophage activity is
unknown. Here we used Nocardia erythropolis ChoD, which is very similar to the
Mtb enzyme (70% identity at the amino-acid level), to evaluate the impact of
bacterial ChoD on the activity of THP-1-derived macrophages in vitro. We found
that ChoD decreased the surface expression of Toll-like receptor type 2 (TLR2)
and complement receptor 3 (CR3) on these macrophages. Flow cytometry and confocal
microscopy showed that ChoD competed with lipoteichoic acid for ligand binding
sites on TLR2 but not on CR3, suggesting that ChoD signaling is mediated via
TLR2. Binding of ChoD to the membrane of macrophages had diverse effects on the
activity of macrophages, activating p38 mitogen activated kinase and stimulating
production of a large amount of interleukin-10. Moreover, ChoD primed macrophages
to enhance the production of reactive oxygen species in response to the phorbol
myristate acetate, which was reduced by "switching off" TLR-derived signaling
through interleukin-1 receptor-associated kinases 1 and 4 inhibition. Our study
revealed that ChoD interacts directly with macrophages via TLR2 and influences
the biological activity of macrophages during the development of the initial
response to infection.
PMID- 25120290
TI - Direct costs associated with chronic kidney disease among type 2 diabetic
patients in India.
AB - The aim of this study was to estimate the direct costs of medical care among
hospitalized type 2 diabetic patients with chronic kidney disease (CKD). A total
of 209 (M:F, 133:76) patients were divided into groups based on the severity of
kidney disease. Group 1 subjects had undergone renal transplantation (n = 12),
group 2 was CKD patients on hemodialysis (n = 45), group 3 was patients with CKD,
prior to end-stage renal disease (ESRD) (n = 66), and group 4 (n = 86) consisted
of subjects without any complications. Details about expenditure per
hospitalization, length of stay during admission, direct medical and nonmedical
cost, expenditure for the previous two years, and source of bearing the
expenditure were recorded in a questionnaire. Diabetic patients with CKD prior to
ESRD spend more per hospitalization than patients without any complications.
[Median ? 12,664 vs. 3,214]. The total median cost of CKD patients on
hemodialysis was significantly higher than other CKD patients (INR 61,170 vs.
12,664). The median cost involved in kidney transplantation was ? 392,920. The
total expenditure for hospital admissions in two years was significantly higher
for dialysis than transplantation. Patients on hemodialysis or kidney
transplantation tend to stay longer as inpatient admissions. The source of funds
for the expenditure was mainly personal savings (46%). The expenditure on
hospital admissions for CKD was considerably higher, and so, there is a need to
develop a protocol on a cost-effective strategy for the treatment of CKD.
PMID- 25120287
TI - Lipid isolated from a Leishmania donovani strain reduces Escherichia coli induced
sepsis in mice through inhibition of inflammatory responses.
AB - Sepsis is the reflection of systemic immune response that manifests in the
sequential inflammatory process in presence of infection. This may occur as a
result of gram-negative bacterial sepsis including Escherichia coli infection
that gives rise to excessive production of inflammatory mediators and causes
severe tissue injuries. We have reported earlier that the lipid of attenuated
Leishmania donovani suppresses the inflammatory responses in arthritis patients.
Using heat killed E. coli stimulated macrophages, we have now investigated the
effect of leishmanial total lipid (LTL) isolated from Leishmania donovani
(MHO/IN/1978/UR6) for amelioration of the inflammatory mediators and
transcriptional factor with suppression of TLR4-CD14 expression. To evaluate the
in vivo effect, E. coli induced murine sepsis model was used focusing on the
changes in different parameter(s) of lung injury caused by sepsis, namely, edema,
vascular permeability, and pathophysiology, and the status of different cytokine
chemokine(s) and adhesion molecule(s). Due to the effect of LTL, E. coli induced
inflammatory cytokine-chemokine(s) levels were significantly reduced in serum and
bronchoalveolar lavage fluid simultaneously. LTL also improved the lung injury
and suppressed the cell adhesion molecules in lung tissue. These findings
indicate that LTL may prove to be a potential anti-inflammatory agent and provide
protection against gram-negative bacterial sepsis with pulmonary impairment.
PMID- 25120291
TI - Frequency and clinicopathological correlations of histopathological variants of
pediatric idiopathic focal segmental glomerulosclerosis.
AB - There is no information on the frequency and clinicopathological correlations of
the histopathological variants of primary focal segmental glomerulosclerosis
(FSGS) in children presenting with idiopathic nephrotic syndrome (INS) in
Pakistan. All consecutive children (<=17 years) who presented with INS, and in
whom the histological diagnosis of FSGS was made on renal biopsies, were included
in this prospective study. Their clinical, laboratory, and histopathological
features at the time of presentation were noted from the case files and the
biopsy reports for analysis and clinicopathological correlations. Out of 138
children, 93 (67.4%) were males and 45 (32.6%) were females. The mean age was
8.95 +/- 4.14 (range: 1.5-17) years. All had NS, with steroid dependant NS (SDNS)
in 45 (32.6%) and steroid resistant NS (SRNS) in 93 (67.4%) cases. Renal
dysfunction at the time of presentation was found in six (4.3%) children. Global
glomerulosclerosis was found in 68 (49.3%) cases. The mean number of glomeruli
involved by segmental scarring was 2.98 +/- 2.44. FSGS, not otherwise specified
(NOS) was the most prevalent variant, comprising 89.1% of all cases. Collapsing
variant comprised 8%, tip variant 1.4%, perihilar 0.7%, and cellular 0.7%.
Hyaline arteriolosclerosis was found in 13 (9.4%) cases. Mild interstitial
fibrosis/tubular atrophy was found in 95 (68.6%) cases, moderate in 18 (13%), and
severe in two (1.4%) cases. In conclusion, FSGS, NOS variant was the highly
prevalent variant, while collapsing type was also found in small but significant
number of cases. Remaining three variants were distinctly rare in our children.
PMID- 25120292
TI - Prospective blood pressure measurement in renal transplant recipients.
AB - Blood pressure (BP) control at home is difficult when managed only with office
blood pressure monitoring (OBPM). In this prospective study, the reliability of
BP measurements in renal transplant patients with OBPM and home blood pressure
monitoring (HBPM) was compared with ambulatory blood pressure monitoring (ABPM)
as the gold standard. Adult patients who had living-related renal transplantation
from March 2007 to February 2008 had BP measured by two methods; OBPM and ABPM at
pretransplantation, 2(nd), 4(th), 6(th), and 9(th) months and all the three
methods: OBPM, ABPM, and HBPM at 6 months after transplantation. A total of 49
patients, age 35 +/- 11 years, on prednisolone, tacrolimus, and mycophenolate
were evaluated. A total of 39 were males (79.6%). Systolic BP (SBP) and diastolic
BP (DBP) measured by OBPM were higher than HBPM when compared with ABPM. When
assessed using OBPM and awake ABPM, both SBP and DBP were significantly
overestimated by OBPM with mean difference of 3-12 mm Hg by office SBP and 6-8 mm
Hg for office DBP. When HBPM was compared with mean ABPM at 6 months both the SBP
and DBP were overestimated by and 7 mm Hg respectively. At 6 months post
transplantation, when compared with ABPM, OBPM was more specific than HBPM in
diagnosing hypertension (98% specificity, Kappa: 0.88 vs. 89% specificity, Kappa:
0.71). HBPM was superior to OBPM in identifying patients achieving goal BP (89%
specificity, Kappa: 0.71 vs. 50% specificity Kappa: 0.54). In the absence of a
gold standard for comparison the latent class model analysis still showed that
ABPM was the best tool for diagnosing hypertension and monitoring patients
reaching targeted control. OBPM remains an important tool for the diagnosis and
management of hypertension in renal transplant recipients. HBPM and ABPM could be
used to achieve BP control.
PMID- 25120293
TI - Renal outcome in biopsy proven cases of graft pyelonephritis.
AB - The incidence, risk factors and outcome of graft pyelonephritis are variably
described in literature. All patients who had been transplanted at our center
between January 2002 and November 2006 and had presented with acute graft
dysfunction were subjected to biopsy. Those patients who had neutrophilic casts
and interstitial inflammation with predominant neutrophils were included in the
study. Out of the 265 patients, 110 were transplanted in the period and underwent
biopsy for graft dysfunction. Out of the 110 patients, 26 had biopsy proven acute
graft pyelonephritis (AGPN). Nine patients had early AGPN (within 6 months) and
the other 17 had late AGPN. Nearly 19% of patients were culture negative and five
patients had no clinical features of urinary tract infection; AGPN being a
surprise finding on biopsy. Among the risk factors, only hepatitis C virus
infection was significantly associated with AGPN. All patients received 4-6 weeks
of antibiotics with at least 3 weeks of parenteral antibiotics. Majority (75%) of
our patients experienced relapse of AGPN. Graft function was significantly lower
6 months after onset when compared to baseline, portending a poor outcome for
these patients. Out of 26, 7 (27%) of our patients had biopsy features of
concomitant acute cellular rejection. The treatment of acute rejection, however,
did not improve the outcome.
PMID- 25120294
TI - Differences among children, adolescents and adults with severe leptospirosis: A
comparative analysis.
AB - Leptospirosis is a zoonosis of global importance caused by Leptospira
interrogans. The aim of this study was to compare the data between children,
adolescents and adults with leptospirosis. This is a retrospective study
including a total of 373 consecutive patients with leptospirosis, admitted to
tertiary hospitals in Northeast of Brazil, from May 1985 to August 2010. The
patients were divided into two groups (age <=21 years and >21 years). The adults
were 304 (81.5%) of the population, with a mean ge of 41 +/- 13 (range 22-84)
years. The pediatric group was 16 +/- 3 (range 9-21) years. Signs and symptoms
where similar between the groups, excepting arrhythmia, which was more frequent
in adults and vomiting, more common in children (16% vs. 0%, P = 0.04 and 65% vs.
79%, P = 0.02), respectively. Adult group presented with higher serum urea (137
vs. 97 mg/dl, P = 0.002) and creatinine (4.3 vs. 3.0 mg/dl, P = 0.007). Acute
kidney injury (AKI) was observed in 80%, mainly in adults (83% vs. 70% P <
0.005). Adults required renal replacement therapy more frequently than children
(38% vs. 11%, P < 0.0001). Mortality was higher in adults (14.8% vs. 2.8%, P =
0.005) and in adults with AKI (93% vs. 7%, P < 0.05). There are important
differences between the adults and children with leptospirosis. AKI was more
frequent in adults and it was associated with increased mortality.
PMID- 25120295
TI - Wilson's disease - A rare cause of renal tubular acidosis with metabolic bone
disease.
AB - We report a 16-year-old boy who presented with weakness of lower limbs. He was
diagnosed to have Wilson's disease, renal tubular acidosis and osteoporosis.
Screening of siblings showed that his younger sister was also affected by the
disease.
PMID- 25120296
TI - An interesting case of primary hypoparathyroidism.
AB - Primary hypoparathyroidism can occur due to an activating mutation of calcium
sensing receptor (CaSR). Most patients remain asymptomatic and therefore not
diagnosed until adulthood. We present a 38-year-old lady who had a history of
muscle cramps since 8 years. She presented with vomiting, abdomen pain and body
ache, showed clinical evidence of hypovolemia, severe hypocalcemia, hypokalemia,
hypomagnesemia, hyperphosphatemia and metabolic alkalosis. Her 24 h urinary
phosphorus was low and 24 h urinary excretion of sodium, potassium and chloride
were high. Her intact parathormone was on the lower side of the normal range. She
improved once we had corrected her biochemical abnormalities. By excluding
acquired causes of hypoparathyroidism, we are able to conclude that this may be a
case of primary hypoparathyroidism due to activating mutation of CaSR.
PMID- 25120297
TI - Thyrocervical artery - jugular fistula following internal jugular venous
catheterization.
AB - Arteriovenous fistula (AVF) is an anomalous communication between an artery and a
vein, caused by an iatrogenic or traumatic etiology. Surgically created upper
limb AVF remains the preferred vascular access for patients on maintenance
hemodialysis. Nonetheless central vein cannulation for hemodialysis is a common
procedure done in patients who need hemodialysis. We incidentally detected a
thyrocervical artery - jugular fistula in a patient on maintenance hemodialysis.
He underwent a successful intra arterial coil embolization of the feeding vessel.
Review of literature has shown that, a thyrocervical artery - internal jugular
vein arteriovenous fistula following a central venous catheterization has not
been reported so far.
PMID- 25120298
TI - IgA dominant postinfectious glomerulonephritis: Report of two cases.
AB - Immunoglobulin A (IgA) dominant postinfectious glomerulonephritis (IgA PIGN) is a
distinct clinical entity increasingly recognized in adult. It usually presents
with reduced glomerular filtration rate, heavy proteinuria, and has unfavorable
prognosis. Immunofluorescence study of renal biopsy specimens have IgA as
dominant or codominant antibody. We encountered two cases of IgA dominant PIGN
recently presenting as rapidly progr essive glomerulonephritis and managed
conservatively. Both the patients are on follow-up and do not have complete
recovery of renal function till date. Long-term follow-up is needed to assess the
progression of the disease in these patients.
PMID- 25120299
TI - Extending the longevity of a complicated arteriovenous fistula using endovascular
intervention.
AB - A brachiocephalic arteriovenous fistula was complicated by a central venous
stenosis, which could not be relieved. A cephalojugular bypass was performed
using an interpositoned graft, which later developed tight stenoses at both ends
of the graft. This was successfully treated with endovascular intervention,
extending the longevity of the vascular access.
PMID- 25120300
TI - Multifocal bacterial osteomyelitis in a renal allograft recipient following
urosepsis.
AB - Non-tubercular bacterial osteomyelitis is a rare infection. We report on a renal
allograft recipient with osteomyelitis complicating urosepsis, manifesting as a
multifocal infection poorly responsive to appropriate antibiotics and surgical
intervention and culminating in graft loss.
PMID- 25120301
TI - Chronic renal failure, hyperkalemia, and colonic ulcers.
PMID- 25120303
TI - Apparent steroid resistance associated with prednisolone suspension.
PMID- 25120302
TI - D-penicillamine-induced membranous nephropathy.
PMID- 25120304
TI - Comment on: Malignant hypertension and nephrotic range proteinuria without
hematuria: IgA nephropathy.
PMID- 25120305
TI - Acute renal failure secondary to ingestion of unknown mercury containing medicine
not due to Ayurvedic medicine.
PMID- 25120306
TI - Immunosupression for patients of endocarditis with glomerulonephritis.
PMID- 25120307
TI - Seminoma in undescended testes presenting with acute renal failure.
PMID- 25120308
TI - Membranous nephropathy and carbamazepine.
PMID- 25120309
TI - Unfounded reports on thyroid cancer.
PMID- 25120310
TI - Ten tips for authors of scientific articles.
AB - Writing a good quality scientific article takes experience and skill. I propose
'Ten Tips' that may help to improve the quality of manuscripts for scholarly
journals. It is advisable to draft first version of manuscript and revise it
repeatedly for consistency and accuracy of the writing. During the drafting and
revising the following tips can be considered: 1) focus on design to have proper
content, conclusion, points compliant with scope of the target journal,
appropriate authors and contributors list, and relevant references from widely
visible sources; 2) format the manuscript in accordance with instructions to
authors of the target journal; 3) ensure consistency and logical flow of ideas
and scientific facts; 4) provide scientific confidence; 5) make your story
interesting for your readers; 6) write up short, simple and attractive sentences;
7) bear in mind that properly composed and reflective titles increase chances of
attracting more readers; 8) do not forget that well-structured and readable
abstracts improve citability of your publications; 9) when revising adhere to the
rule of 'First and Last' - open your text with topic paragraph and close it with
resolution paragraph; 10) use connecting words linking sentences within a
paragraph by repeating relevant keywords.
PMID- 25120311
TI - Role of innate immunity in the pathogenesis of type 1 and type 2 diabetes.
AB - The importance of innate immunity in host defense is becoming clear after
discovery of innate immune receptors such as Toll-like receptor or Nod-like
receptor. Innate immune system plays an important role in diverse pathological
situations such as autoimmune diseases. Role of innate immunity in the
pathogenesis of metabolic disorders such as type 2 diabetes, metabolic syndrome
or atherosclerosis that has not been previously considered as inflammatory
disorders, is also being appreciated. Here, the role of innate immunity in the
development of type 1 diabetes, a classical organ-specific autoimmune disease,
and type 2 diabetes will be discussed, focusing on the role of specific innate
immune receptors involved in these disease processes.
PMID- 25120312
TI - Withaferin A-caused production of intracellular reactive oxygen species modulates
apoptosis via PI3K/Akt and JNKinase in rabbit articular chondrocytes.
AB - Withaferin A (WFA) is known as a constituent of Ayurvedic medicinal plant,
Withania somnifera, and has been used for thousands of years. Although WFA has
been used for the treatment of osteoarthritis (OA) and has a wide range of
biochemical and pharmacologic activities, there are no findings suggesting its
properties on chondrocytes or cartilage. The aim of the present study is to
investigate the effects of WFA on apoptosis with focus on generation of
intracellular reactive oxygen species (ROS). Here we showed that WFA
significantly increased the generation of intracellular ROS in a dose-dependent
manner. We also determined that WFA markedly leads to apoptosis as evidenced by
accumulation of p53 by Western blot analysis. N-Acetyl-L-Cystein (NAC), an
antioxidant, prevented WFA-caused expression of p53 and inhibited apoptosis of
chondrocytes. We also found that WFA causes the activation of PI3K/Akt and
JNKinase. Inhibition of PI3K/Akt and JNKinase with LY294002 (LY)/triciribine (TB)
or SP600125 (SP) in WFA-treated cells reduced accumulation of p53 and inhibited
fragmented DNA. Our findings suggested that apoptosis caused by WFA-induced
intracellular ROS generation is regulated through PI3K/Akt and JNKinase in rabbit
articular chondrocytes.
PMID- 25120313
TI - Clinicopathological features of rare BRAF mutations in Korean thyroid cancer
patients.
AB - The most common BRAF mutation in thyroid cancer is c.1799T>A (p.Val600Glu), and
other BRAF mutations are rarely reported. We investigated the clinicopathological
features of thyroid cancer with rare BRAF mutations. A total of 2,763 patients
with thyroid cancer underwent molecular testing by direct DNA sequencing for
mutations in BRAF exon 15. Among them, 2,110 (76.4%) had BRAF mutations. The
c.1799T>A mutation was found in 2,093 (76.9%) of 2,722 papillary carcinomas and
in one of 7 medullary carcinomas. Sixteen cases (0.76%) harbored rare mutation
types. Five cases had single-nucleotide substitutions, 5 cases had small in-frame
deletion or insertion, and one harbored a two-nucleotide substitution. Of these
mutations, 2 were novel (c.1797_1798insGAGACTACA, c.[1799T>A; 1801_1812del]). The
c.1801A>G mutation was identified in 4 follicular variant papillary carcinomas
and one follicular carcinoma. None of the patients with the c.1801A>G mutation
showed extrathyroidal extension or lymph node metastasis. The prevalence of rare
BRAF mutations was 0.76% of all BRAF-positive thyroid cancers, and the rare
mutations were associated with less aggressive pathologic features. Although BRAF
mutations are detected exclusively in papillary carcinoma, they are also found in
medullary carcinoma and follicular carcinoma. [Corrected]
PMID- 25120314
TI - Influenza vaccination and associated factors among Korean cancer survivors : a
cross-sectional analysis of the Fourth & Fifth Korea National Health and
Nutrition Examination Surveys.
AB - Influenza vaccination is important for cancer survivors, a population with
impaired immunity. This study was designed to assess influenza vaccination
patterns among Korean cancer survivors. In this cross-sectional analysis, data
were obtained from standardized questionnaires from 943 cancer survivors and
41,233 non-cancer survivors who participated in the Fourth and Fifth Korea
National Health and Nutrition Examination Surveys (2007-2011). We identified the
adjusted influenza vaccination rates and assessed factors associated with
influenza vaccination using multivariate logistic regression. Cancer survivors
tended to have a higher adjusted influenza vaccination rate than the general
population. The rates for influenza vaccination in specific cancer types such as
stomach, hepatic, colon, and lung cancers were significantly higher than non
cancer survivors. Among all cancer survivors, those with chronic diseases,
elderly subjects, and rural dwellers were more likely to receive influenza
vaccination; those with cervical cancer were less likely to receive influenza
vaccination. Cancer survivors were more likely to receive influenza vaccinations
than non-cancer survivors, but this was not true for particular groups,
especially younger cancer survivors. Cancer survivors represent a sharply growing
population; therefore, immunization against influenza among cancer survivors
should be concerned as their significant preventative healthcare services.
PMID- 25120315
TI - Sirolimus conversion efficacy for graft function improvement and histopathology
in renal recipients with mild to moderate renal insufficiency.
AB - This study was designed to evaluate whether sirolimus (SRL) conversion
effectively improves renal function and histopathology in calcineurin inhibitor
(CNI)-treated renal recipients with mild to moderate renal insufficiency. SRL
conversion from CNI was performed in patients who underwent kidney
transplantation from 6 months to 5 yr prior to screening. Forty-five patients
were enrolled. The effect of SRL conversion on graft function was evaluated, and
protocol biopsies were performed preconversion and 1 yr after conversion. Overall
graft function after SRL conversion gradually improved, and the improvement in
renal function was closely associated with the shorter duration of CNI exposure.
When we divided the patients by the duration of CNI exposure, the patients with
less than 1 yr of CNI exposure demonstrated significant improvement, but patients
with a greater than 1 yr CNI exposure did not exhibit significant improvement. In
contrast, protocol biopsies demonstrated no significant improvements in the
modified "ah" score or other Banff scores after SRL conversion. Furthermore, the
duration of CNI treatment prior to SRL conversion was not associated with
histological findings 1 yr after SRL conversion. SRL conversion improved graft
function in renal recipients with mild to moderate renal insufficiency, but this
effect is not accompanied by histological improvement.
PMID- 25120316
TI - Four-week effects of allopurinol and febuxostat treatments on blood pressure and
serum creatinine level in gouty men.
AB - The aim of this study was to observe the effects of uric acid lowering therapy
(UALT), febuxostat and allopurinol, on blood pressure (BP) and serum creatinine
level. Post-hoc data were derived from a phase-III, randomised, double-blind, 4
week trial of male gouty patients that compared the safety and efficacy of
febuxostat and allopurinol in adults with gout. The subjects were randomly
assigned to one of five groups, 35-37 in each group (febuxostat: 40, 80, 120
mg/d; allopurinol: 300 mg/d; control group: placebo). Blood pressure and serum
creatinine level were measured at baseline and at weeks 2 and 4. Diastolic BP and
creatinine level had decreased significantly in the UALT groups compared to the
control group at week 4. Diastolic BP had decreased significantly in the
allopurinol group and serum creatinine level had decreased significantly in the
febuxostat groups at week 4. After adjusting for confounding variables, serum
uric acid changes were found to be significantly correlated with changes in serum
creatinine level but were not associated with changes in systolic or diastolic
BP. UALT in gouty subjects significantly decreased diastolic BP and serum
creatinine level. Changes in uric acid were significantly correlated with those
in serum creatinine level, suggesting the feasibility of renal function
improvement through UALT in gouty men.
PMID- 25120317
TI - The risk of osteoporotic fractures according to the FRAX model in Korean patients
with rheumatoid arthritis.
AB - The aim of the current study is to identify patients without osteoporosis who met
the criteria of the fracture risk assessment tool (FRAX) of the National
Osteoporosis Foundation (NOF) only. The incidence of fractures was investigated
in patients who met only the FRAX criteria of the NOF and patients who presented
osteoporosis. Five hundred and forty five patients with rheumatoid arthritis who
visited a single center were recruited in Korea. In the follow-up period of
median 30 months, the new onset of fractures was investigated. Of 223 patients
who have no osteoporosis, 39 (17.4%) satisfied the FRAX criteria for
pharmacological intervention. During the follow-up period, 2 new onset fractures
occurred in patients who met only the FRAX criteria and 22 new onset fractures
did in patients with osteoporosis by bone mineral density. The incidence rate for
new onset fractures of patients who met only the FRAX criteria was with 295.93
per 10,000 person-years higher than in the general population with 114.99 per
10,000 person-years. Patients who met the FRAX criteria of the NOF only need
pharmacological intervention because their numbers of incidence for new onset
fractures are similar to those of patients with osteoporosis by BMD.
PMID- 25120318
TI - Follow-up testing of interferon-gamma release assays are useful in ankylosing
spondylitis patients receiving anti-tumor necrosis factor alpha for latent
tuberculosis infection.
AB - We evaluated the utility of follow-up interferon-gamma release assays (IGRAs) for
the diagnosis of reactivation of latent tuberculosis infection (LTBI) or new
tuberculosis in ankylosing spondylitis (AS) patients receiving anti-tumor
necrosis factor alpha (anti-TNFalpha). The study participants (n=127) had a
negative IGRA screening before receiving anti-TNFalpha and were evaluated by
follow-up IGRA. We retrospectively examined data of the subjects according to
age, gender, tuberculosis prophylaxis, concomitant medications, IGRA conversion
and anti-TNFalpha, including type and treatment duration. The median duration of
anti-TNFalpha was 21.5 months, and the median age was 35.3 yr. Of the 127
patients, IGRA conversion was found in 10 patients (7.9%). There was no
significant variation between IGRA conversion rate and any risk factors except
for age. IGRA conversion rate was not significantly different between AS and
rheumatoid arthritis (P=0.12). IGRA conversion was observed in AS patients
receiving anti-TNFalpha in Korea. A follow-up IGRA test can be helpful for
identifying LTBI or new tuberculosis in AS patients receiving anti-TNFalpha.
PMID- 25120319
TI - Impact of multimodality approach for patients with leptomeningeal metastases from
solid tumors.
AB - The purpose of this study was to evaluate treatment patterns, outcome and
prognosticators for patients with leptomeningeal metastases from solid tumor.
Medical records of 80 patients from January 1, 2004 to May 31, 2011 were
retrospectively reviewed. Most frequent site of origin was the lung (59%)
followed by the breast (25%). Most patients were treated with intrathecal
chemotherapy (90%) and/or whole brain radiotherapy (67.5%). Systemic therapy was
offered to 27 patients (33.8%). Percentage of patients treated with single, dual,
and triple modality were 32.5%, 43.8%, and 23.8%, respectively. Median survival
was 2.7 months and 1 yr survival rate was 11.3%. Multivariate analysis showed
that negative cerebrospinal fluid cytology, fewer chemotherapy regimen prior to
leptomeningeal metastases, whole brain radiotherapy, systemic therapy, and
combined modality treatment (median survival; single 1.4 vs. dual 2.8 vs. triple
8.3 months, P<0.001) had statistical significance on survival. Subgroup analysis
of non-small cell lung cancer (NSCLC) patients showed that targeted therapy had
significant independent impact on survival (median survival; 10.5 vs. 3.0 months,
P=0.008). Unlike previous reports, survival of patients with NSCLC primary was
comparable to breast primary. Furthermore, combined modality treatment for all
patients and additionally targeted therapy for NSCLC patients should be
considered in the treatment of leptomeningeal metastases from solid tumor.
PMID- 25120320
TI - Acute kidney injury after using contrast during cardiac catheterization in
children with heart disease.
AB - Acute kidney injury (AKI) is closely associated with the mortality of
hospitalized patients and long-term development of chronic kidney disease,
especially in children. The purpose of our study was to assess the evidence of
contrast-induced AKI after cardiac catheterization in children with heart disease
and evaluate the clinical usefulness of candidate biomarkers in AKI. A total of
26 children undergoing cardiac catheterization due to various heart diseases were
selected and urine and blood samples were taken at 0 hr, 6 hr, 24 hr, and 48 hr
after cardiac catheterization. Until 48 hr after cardiac catheterization, there
was no significant increase in serum creatinine level in all patients. Unlike
urine kidney injury molecule-1, IL-18 and neutrophil gelatinase-associated
lipocalin, urine liver-type fatty acid-binding protein (L-FABP) level showed
biphasic pattern and the significant difference in the levels of urine L-FABP
between 24 and 48 hr. We suggest that urine L-FABP can be one of the useful
biomarkers to detect subclinical AKI developed by the contrast before cardiac
surgery.
PMID- 25120321
TI - Comparison of Korean COPD guideline and GOLD initiative report in term of acute
exacerbation: a validation study for Korean COPD guideline.
AB - The purpose of this study was to compare the Korean COPD guideline to GOLD
consensus report in terms of acute exacerbation. A total of 361 patients were
enrolled in this study, and 16.9% of them experienced acute exacerbation during
the follow-up. A total of 6.3% of patients in GOLD A, 9.5% in GOLD B, 7.7% in
GOLD C and 17.0% of GOLD D experienced exacerbation during the first year of
follow-up, respectively (P=0.09). There was no one who experienced exacerbation
during the first year of follow-up in the Korean group 'ga'. The 12-month
exacerbation rates of Korean group 'na' and 'da' were 4.5% and 16.0%,
respectively (P<0.001). We explore the experience of exacerbation in patients
with change of their risk group after applying Korean COPD guideline. A total of
16.0% of the patients who were reclassified from GOLD A to Korean group 'da'
experienced acute exacerbation,and 15.3% from GOLD B to Korean group 'da'
experienced acute exacerbation. In summary, the Korean COPD guideline is useful
to differentiate the high risk from low risk for exacerbation in terms of
spirometry. This indicates that application of Korean COPD guideline is
appropriate to treat Korean COPD patients.
PMID- 25120322
TI - Relationship of liver stiffness and controlled attenuation parameter measured by
transient elastography with diabetes mellitus in patients with chronic liver
disease.
AB - High prevalence of diabetes mellitus in patients with liver cirrhosis has been
reported in many studies. The aim of our study was to evaluate the relationship
of hepatic fibrosis and steatosis assessed by transient elastography with
diabetes in patients with chronic liver disease. The study population consisted
of 979 chronic liver disease patients. Liver fibrosis and steatosis were assessed
by liver stiffness measurement (LSM) and controlled attenuation parameter (CAP)
on transient elastography. Diabetes was diagnosed in 165 (16.9%) of 979 patients.
The prevalence of diabetes had significant difference among the etiologies of
chronic liver disease. Higher degrees of liver fibrosis and steatosis, assessed
by LSM and CAP score, showed higher prevalence of diabetes (F0/1 [14%], F2/3
[18%], F4 [31%], P<0.001; S0/1 [15%], S2 [17%], S3 [26%], P=0.021). Multivariate
analysis showed that the independent predictive risk factors for diabetes were
hypertension (OR, 1.98; P=0.001), LSM F4 (OR, 1.86; P=0.010), male gender (OR,
1.60; P=0.027), and age>50 yr (OR, 1.52; P=0.046). The degree of hepatic fibrosis
but not steatosis assessed by transient elastography has significant relationship
with the prevalence of diabetes in patients with chronic liver disease.
PMID- 25120323
TI - KISS1 gene polymorphisms in Korean girls with central precocious puberty.
AB - Kisspeptin/G-protein couple receptor-54 (GPR54) system plays a key role in the
activation of the gonadotropic axis at puberty. Central precocious puberty (CPP)
is caused by the premature activation of hypothalamic gonadotropin-releasing
hormone secretion. This study was aimed to identify KISS1 gene variations and to
investigate the associations between KISS1 gene variations and CPP in Korean
girls. All coding exons of KISS1 gene were sequenced in Korean girls with CPP (n
= 143) and their healthy controls (n = 101). Nine polymorphisms were identified
in KISS1 gene. A novel single-nucleotide polymorphism (SNP), 55648176 T/G, was
identified for the first time. SNP 55648184 C/G and 55648186 -/T were detected
more frequently in CPP group than in control group. SNP 55648176 T/G was detected
less frequently in CPP group than in control group. Haplotype GGGC-ACCC was
detected less frequently in CPP group. The genetic variations of KISS1 gene can
be contributing factors of development of CPP. The association between the gene
variations and CPP should be validated by further evidence obtained from large
scaled and functional studies.
PMID- 25120324
TI - Early prophylactic versus late selective use of surfactant for respiratory
distress syndrome in very preterm infants: a collaborative study of 53 multi
center trials in Korea.
AB - Pulmonary surfactant (PS) therapy was proven to be highly successful for the
treatment of respiratory distress syndrome in premature infants. As a results,
early prophylactic (EP) PS therapy has been introduced recently in Europe, the US
and Korea. However, no multi-center study was compared EP and late selective (LS)
PS therapies in Korea. We performed a retrospective multi-center study to compare
the outcomes of EP and LS PS therapies in very preterm infants. We analyzed
clinical morbidity and mortality for 1,291 infants in 2010 (LS group) and 1,249
infants in 2011 (EP group); the infants were born <30 weeks of gestation and had
birth weight <=1,250 g, and were chosen from 53 neonatal intensive care units in
Korea. Compared to the LS group (22.5%), the overall mortality was better in the
EP group (19.9%) and there was no increased need for retreatment.There were
additional benefits in the EP group such as fewer associated complications. To
the best of knowledge, our study is the first nationwide Korean study to compare
the outcomes of EP and LS therapies, and it provides evidences that EP PS therapy
is important in very preterm infants to improve for survival and reduce
morbidities.
PMID- 25120325
TI - Effect of renal insufficiency on stone recurrence in patients with urolithiasis.
AB - The study was designed to assess the relationship between glomerular filtration
rate (GFR) and urinary stone-forming constituents, and to assess the effect of
renal insufficiency on stone recurrence risk in first stone formers (SF).
Baseline serum creatinine levels were obtained, and renal insufficiency was
defined as creatinine clearance <=60 mL/min (Cockroft-Gault). This retrospective
case-control study consists of 342 first SF; 171 SF with normal renal function
were selected with 1:1 propensity scores matched to 171 SF with renal
insufficiency. Urinary metabolic evaluation was compared to renal function. GFR
was positively correlated with urinary calcium, uric acid, and citrate excretion.
Subjects with renal insufficiency had significantly lower urinary calcium, uric
acid, and citrate excretion than those with normal renal function, but not urine
volume. With regard to urinary metabolic abnormalities, similar results were
obtained. SF with renal insufficiency had lower calcium oxalate supersaturation
indexes and stone recurrence rates than SF with normal renal function. Kaplan
Meier curves showed similar results. In conclusion, GFR correlates positively
with urinary excretion of stone-forming constituents in SF. This finding implies
that renal insufficiency is not a risk factor for stone recurrence.
PMID- 25120326
TI - Neuropathic pain model of peripheral neuropathies mediated by mutations of glycyl
tRNA synthetase.
AB - Charcot-Marie-Tooth disease (CMT) is the most common inherited motor and sensory
neuropathy. Previous studies have found that, according to CMT patients,
neuropathic pain is an occasional symptom of CMT. However, neuropathic pain is
not considered to be a significant symptom associated with CMT and, as a result,
no studies have investigated the pathophysiology underlying neuropathic pain in
this disorder. Thus, the first animal model of neuropathic pain was developed by
our laboratory using an adenovirus vector system to study neuropathic pain in
CMT. To this end, glycyl-tRNA synthetase (GARS) fusion proteins with a FLAG-tag
(wild type [WT], L129P and G240R mutants) were expressed in spinal cord and
dorsal root ganglion (DRG) neurons using adenovirus vectors. It is known that
GARS mutants induce GARS axonopathies, including CMT type 2D (CMT2D) and distal
spinal muscular atrophy type V (dSMA-V). Additionally, the morphological
phenotypes of neuropathic pain in this animal model of GARS-induced pain were
assessed using several possible markers of pain (Iba1, pERK1/2) or a marker of
injured neurons (ATF3). These results suggest that this animal model of CMT using
an adenovirus may provide information regarding CMT as well as a useful strategy
for the treatment of neuropathic pain.
PMID- 25120328
TI - Association between bone mineral density and clinical consequences: cross
sectional study of Korean postmenopausal women in an orthopaedic outpatient
clinic.
AB - This study is to identify the characteristics of BMD and the related clinical
consequences through a nationwide, consecutive, cross-sectional study. A total of
1,281 postmenopausal women was enrolled nationwide and underwent measurement for
BMD using dual energy x-ray absorptiometry. Following the T-spine and L-spine
plane radiography, they were evaluated for vertebral fracture by a semi
quantitative method using the Genant's method. Relationship between BMD and
osteoporotic fracture and a degree of deformity in vertebral fracture, treatment
history in osteoporosis and the EQ-5D was analyzed. The distribution of the
normal, osteopenia and osteoporosis group was 25.9%, 37.0%, and 37.2% in lumbar
spine, and 31.4%, 45.3%, and 23.3% in femur neck, respectively. BMD in subjects
with symptomatic or asymptomatic vertebral fracture was significantly lower than
those without fracture. The femur neck and total hip BMDs were significantly
lower in hip fracture group (0.646 g/cm(2) and 0.643 g/cm(2), respectively) and
wrist fracture group (0.661 g/cm(2) and 0.712 g/cm(2), respectively) than in
subjects without fracture (0.721 g/cm(2) and 0.712 g/cm(2), respectively). The
BMD was significantly lower with more severe degree of deformity in vertebral
fracture and lower scores in mobility, usual activities and pain/discomfort of
the EQ-5D. In Korean postmenopausal women, the prevalence of osteoporosis and
vertebral, hip and wrist fracture increase and quality of life decreases with
lower BMD.
PMID- 25120327
TI - The influence of depression, anxiety and somatization on the clinical symptoms
and treatment response in patients with symptoms of lower urinary tract symptoms
suggestive of benign prostatic hyperplasia.
AB - This is the first study to investigate the influence of depression, anxiety and
somatization on the treatment response for lower urinary tract symptoms/benign
prostatic hyperplasia (LUTS/BPH). The LUTS/BPH patients were evaluated with the
Korean versions of the International Prostate Symptom Score (IPSS), the Patient
Health Questionnaire-9 (PHQ-9), the 7-item Generalized Anxiety Disorder Scale
(GAD-7) and the PHQ-15. The primary endpoint was a responder rate defined by the
total score of IPSS (<= 7) at the end of treatment. The LUTS/BPH severity was
significantly higher in patients with depression (whole symptoms P = 0.024;
storage sub-symptom P = 0.021) or somatization (P = 0.024) than in those without,
while the quality of life (QOL) was significantly higher in patients with anxiety
(P = 0.038) than in those without. Anxious patients showed significantly higher
proportion of non-response (odds ratio [OR], 3.294, P = 0.022) than those
without, while somatic patients had a trend toward having more non-responders
(OR, 2.552, P = 0.067). Our exploratory results suggest that depression, anxiety
and somatization may have some influences on the clinical manifestation of
LUTS/BPH. Further, anxious patients had a lower response to treatment in patients
with LUTS/BPH. Despite of limitations, the present study demonstrates that
clinicians may need careful evaluation of psychiatric symptoms for proper
management of patients with LUTS/BPH.
PMID- 25120330
TI - Transplantation of a horseshoe kidney found during harvest operation of a
cadaveric donor: a case report.
AB - A 34-yr-old female was diagnosed as being brain dead. Preoperative ultrasound
revealed no abnormal focal lesions. However, the horseshoe kidney was identified
during organ harvest. En bloc nephrectomy was performed. The kidney was divided
at the midline of isthmus. The divided right kidney was discarded due to numerous
arteries and veins. The divided left kidney was transplanted. After declamping,
the kidney was well perfused and started clearing. Resistive index was 0.72.
Glomerular filtration ratio was 84.69 mL/min on postoperative day 14. The
horseshoe kidney can be successfully transplanted and could be a good solution
for the shortage of organ donors.
PMID- 25120329
TI - Aminophylline partially prevents the decrease of body temperature during
laparoscopic abdominal surgery.
AB - Aminophylline can elicit thermogenesis in rats or increase metabolic rate during
cold stress in lambs. We tested the hypothesis that aminophylline would reduce
the change in core body temperature during laparoscopic abdominal surgery
requiring pneumoperitoneum. Fifty patients were randomly divided into an
aminophylline group (n=25) and a saline control group (n=25). Esophageal
temperature, index finger temperature, and hemodynamic variables, such as mean
blood pressure and heart rate, were measured every 15 min during sevoflurane
anesthesia. In the aminophylline group, esophageal temperatures at T45 (36.1+/
0.38 vs. 35.7+/-0.29, P=0.024), T60 (36.0+/-0.39 vs. 35.6+/-0.28, P=0.053), T75
(35.9+/-0.34 vs. 35.5+/-0.28, P=0.025), T90 (35.8+/-0.35 vs. 35.3+/-0.33,
P=0.011), and T105 (35.8+/-0.36 vs. 35.1+/-0.53, P=0.017) and index finger
temperatures at T15 (35.8+/-0.46 vs. 34.9+/-0.33, P<0.001), T30 (35.7+/-0.36 vs.
35.0+/-0.58, P=0.029), T45 (35.8+/-0.34 vs. 35.2+/-0.42, P=0.020), T60 (35.7+/
0.33 vs. 34.9+/-0.47, P=0.010), T75 (35.6+/-0.36 vs. 34.8+/-0.67, P=0.028), T90
(35.4+/-0.55 vs. 34.4+/-0.89, P=0.042), and T105 (34.9+/-0.53 vs. 33.9+/-0.85,
P=0.024) were significantly higher than in the saline control group.
Aminophylline is effective in maintaining the core temperature through a
thermogenic effect, despite reduced peripheral thermoregulatory vasoconstriction.
PMID- 25120331
TI - Acute pancreatitis induced by methimazole treatment in a 51-year-old korean man:
a case report.
AB - Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse
reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain,
two weeks after commencement on MMI for the treatment of Graves' disease. There
was no evidence of agranulocytosis, and fever subsided soon after stopping MMI
treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain
and fever developed again. His symptoms, biochemical, and imaging studies were
compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical
improvement. This is the first case of MMI-induced acute pancreatitis in Korea.
Clinicians should be aware of the rare but possible MMI-induced pancreatitis in
patients complaining of fever and abdominal pain.
PMID- 25120332
TI - Trends and risk factors of the epidemic of charcoal burning suicide in a recent
decade among Korean people.
AB - The aims of this study were to analyze annual trends of charcoal burning (CB)
suicide, 2000 to 2011, and to examine the risk factors of CB suicide in Korea.
Data on suicides (n=138,938) were obtained from the Statistics Korea. The
proportion of CB suicides among all suicide deaths reported was 0.7% (84 cases)
in 2007, and since 2008 it has rapidly increased to 7.9% (1,251 cases) in 2011.
Of significant risk factors of CB suicide, the presence of the media report of
Ahn's suicide was the greatest risk factor (adjusted odds ratio, 11.69; 95% CI,
10.30-13.23) of the initial phase of the continuing CB suicides since 2008.
Korean Government should urgently consider effective measures against CB suicide,
including enforced media regulations on reporting such suicides.
PMID- 25120333
TI - Susceptibility of Escherichia coli from community-acquired urinary tract
infection to fosfomycin, nitrofurantoin, and temocillin in Korea.
AB - With increase of multi-drug resistant Escherichia coli in community-acquired
urinary tract infections (CA-UTI), other treatment option with a therapeutic
efficacy and a low antibiotic selective pressure is necessary. In this study, we
evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin
(FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim
sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal
inhibitory concentrations were determined by E-test or agar dilution method
according to the Clinical and Laboratory Standards Institute guidelines, using
346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011.
FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO
96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and
SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an
activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic
option for uncomplicated CA-UTI, especially for lower UTI.
PMID- 25120337
TI - Biometric risk factors for corneal neovascularization associated with hydrogel
soft contact lens wear in Korean myopic patients.
AB - PURPOSE: To investigate the biometric risk factors for corneal surface
complications associated with hydrogel soft contact lens (SCL) fitting in myopic
patients in Korea. METHODS: This is a retrospective case-control study. The
records of 124 subjects (124 eyes) who wore SCLs on a daily basis were reviewed.
Thirty-one patients (31 eyes) who were diagnosed with corneal neovascularization
(NV) while wearing SCLs were included in the complication group. Ninety-three age
and sex-matched patients (93 eyes) who wore SCLs, who did not have corneal NV
and who visited our clinic for correction of refractive errors were included in
the control group. The degree of spherical equivalent, astigmatism and corneal
base curve radius (BCR) were compared in both groups. RESULTS: Patients with NV
exhibited poorer best corrected visual acuity and more myopia than controls (p =
0.008 and 0.006, respectively). In univariate analysis, highly myopic patients (
9 diopters [D] or higher) were more likely to experience NV (odds ratio [OR],
2.232; 95% confidence interval [CI], 1.602 to 3.105). High astigmatism (>=2 D)
increased the risk of complications (OR, 2.717; 95% CI, 1.141 to 6.451). Steep
cornea, in which BCR was <7.5 mm, also raised the risk of complications (OR,
4.000; 95% CI, 1.661 to 9.804). Flat cornea was not a risk factor for the
development of NV. CONCLUSIONS: High myopia, high astigmatism, and steep cornea
seemed to be risk factors in the development of corneal NV in SCL wearers.
PMID- 25120336
TI - Higher order aberrations of the corneal surface after laser subepithelial
keratomileusis.
AB - PURPOSE: To evaluate the changes of higher order aberrations (HOAs) before and
after laser subepithelial keratomileusis (LASEK) and to analyze the influence of
tear film instability on HOAs of the corneal surface after LASEK. METHODS: In
this cross-sectional study, 31 patients who underwent LASEK were divided into dry
eye (16 patients, 32 eyes) and non-dry eye groups (15 patients, 30 eyes).
Uncorrected distance visual acuity, spherical equivalent refraction, ablation
depth, tear film parameters and Ocular Surface Disease Index (OSDI) questionnaire
scores were evaluated in both groups. Total HOA root mean square (RMS), third
order coma, third-order trefoil and fourth-order spherical aberration (SA) of the
corneal surface immediately and at 10 seconds after blinking were measured before
and after surgery. RESULTS: The total HOA RMS, coma, trefoil and SA significantly
increased after LASEK compared with preoperative values in both groups. In the
dry eye group, total HOA RMS, coma and trefoil significantly increased except for
SA at 10 seconds after blinking compared with those measured immediately after
blinking. In addition, the changes of total HOA RMS, coma and trefoil were
negatively correlated with tear film break-up time (R = -0.420, -0.473 and
0.439, respectively), but positively correlated with OSDI score (R = 0.433, 0.499
and 0.532, respectively). In the non-dry eye group, there were no significant
differences between HOAs measured at 10 seconds after blinking and those measured
immediately after blinking. CONCLUSIONS: The HOAs including coma, trefoil and SA
significantly increased after LASEK. The tear film instability in the dry eye can
be associated with more deterioration of the optical quality after LASEK, due to
more significant increase of total HOA RMS, coma and trefoil.
PMID- 25120338
TI - Efficacy of intravitreal anti-vascular endothelial growth factor or steroid
injection in diabetic macular edema according to fluid turbidity in optical
coherence tomography.
AB - PURPOSE: To determine if short term effects of intravitreal anti-vascular
endothelial growth factor or steroid injection are correlated with fluid
turbidity, as detected by spectral domain optical coherence tomography (SD-OCT)
in diabetic macular edema (DME) patients. METHODS: A total of 583 medical records
were reviewed and 104 cases were enrolled. Sixty eyes received a single
intravitreal bevacizumab injection (IVB) on the first attack of DME and 44 eyes
received triamcinolone acetonide treatment (IVTA). Intraretinal fluid turbidity
in DME patients was estimated with initial intravitreal SD-OCT and analyzed with
color histograms from a Photoshop program. Central macular thickness and visual
acuity using a logarithm from the minimum angle of resolution chart, were
assessed at the initial period and 2 months after injections. RESULTS: Visual
acuity and central macular thickness improved after injections in both groups. In
the IVB group, visual acuity and central macular thickness changed less as the
intraretinal fluid became more turbid. In the IVTA group, visual acuity underwent
less change while central macular thickness had a greater reduction (r = -0.675,
p = 0.001) as the intraretinal fluid was more turbid. CONCLUSIONS: IVB and IVTA
injections were effective in reducing central macular thickness and improving
visual acuity in DME patients. Further, fluid turbidity, which was detected by SD
OCT may be one of the indexes that highlight the influence of the steroid
dependent pathogenetic mechanism.
PMID- 25120339
TI - Intravitreal anti-vascular endothelial growth factor versus observation in acute
central serous chorioretinopathy: one-year results.
AB - PURPOSE: To evaluate the efficacy of anti-vascular endothelial growth factor
(VEGF) compared with observation for treating acute central serous
chorioretinopathy (CSC). METHODS: A retrospective study of 36 patients with acute
CSC, including 21 patients treated with anti-VEGF (anti-VEGF group) and 15
patients with observation (observation group). Patients in the anti-VEGF group
received a single dose of bevacizumab or ranibizumab at baseline. Best-corrected
visual acuity (BCVA), central foveal thickness (CFT) and resolution of subretinal
fluid (SRF) on optical coherence tomography (OCT) were assessed. The integrity of
the foveal inner segment/outer segment (IS/OS) line at 12 months was also
analyzed. RESULTS: Resolution of SRF was achieved in 20 of 21 eyes in the anti
VEGF group and in 12 of 15 eyes in the observation group (p = 0.151). Mean BCVA
and CFT were not different between the two groups at 12 months (p > 0.05). The
amount of change in BCVA, however, differed significantly between the groups (p =
0.044). Final OCT more frequently detected the foveal IS/OS line in the anti-VEGF
group than in the observation group (p = 0.012). CONCLUSIONS: In terms of BCVA,
anti-VEGF and observation only had similar therapeutic effects in acute CSC
patients. In some patients, however, the rapid resolution of SRF by anti-VEGF
might reduce the risk of photoreceptor degeneration and improve long-term visual
acuity.
PMID- 25120341
TI - Depth and area of retinal nerve fiber layer damage and visual field correlation
analysis.
AB - PURPOSE: To evaluate the relationship between the structural damage as assessed
by time-domain optical coherence tomography (OCT) and functional changes in
glaucoma. METHODS: In total, 190 patients with normal tension glaucoma or primary
open angle glaucoma were included in this study. The thickness of retinal nerve
fiber layer (RNFL) around the optic disc and the area of RNFL defect were
determined using OCT scans. The relationships between the RNFL thickness or area
of the defect and visual field (VF) indices were assessed using the Lowess
function, regression analysis and partial Spearman correlation. The differences
between these associations depending on the stage of VF damage were further
analyzed. Age, optic disc size, refraction, central corneal thickness and the
presence of systemic disease were corrected for in order to exclude confounding
factors. RESULTS: A logarithmic scale of RNFL thickness showed a negative linear
relationship with VF indices. The area of the RNFL defect showed a weak
correlation with the pattern of standard deviation, whereas the remnant RNFL
thickness was moderately correlated with the pattern of standard deviation
(partial Spearman correlation coefficient, 0.39, -0.47, respectively; p <
0.0001). Many outliers were detected in the Lowess-plotted graphs. Multiplication
of the area and the inverted RNFL thickness showed a moderately correlated
logarithmic relationship with the VF indices (partial Spearman correlation
coefficient, 0.46; 95% confidence interval, 0.34 to 0.57; p < 0.0001). In the
severe stage of VF damage, correlation between the area of the RNFL defect and
mean deviation was significantly greater than in other stages (partial Spearman
correlation coefficient, -0.66; p = 0.02). CONCLUSIONS: The thickness of the RNFL
had a negative logarithmic correlation with the VF indices and was more relevant
to the VF indices than the area of the RNFL defect, as measured by OCT.
PMID- 25120340
TI - Assessment of macular ganglion cell loss patterns in neurologic lesions that
mimic glaucoma.
AB - PURPOSE: To evaluate patterns of macular retinal ganglion cell (RGC) loss
measured by spectral domain optical coherence tomography in patients with
neurologic lesions mimicking glaucoma. METHODS: We evaluated four patients with
neurological lesions who showed characteristic patterns of RGC loss, as
determined by ganglion cell thickness (GCT) mapping. RESULTS: Case 1 was a 30
year-old man who had been treated with glaucoma medication. A left homonymous
vertical pattern of RGC loss was observed in his GCT map and a past brain
magnetic resonance imaging (MRI) revealed a hemorrhagic lesion around the right
optic radiation. Case 2 was a 72-year-old man with a pituitary adenoma who had a
binasal vertical pattern of RGC loss that corresponded with bitemporal
hemianopsia. Case 3 was a 77-year-old man treated for suspected glaucoma. His GCT
map showed a right inferior quadratic pattern of loss, indicating a right
superior homonymous quadranopsia in his visual field (VF). His brain MRI revealed
a left posterior cerebral artery territory infarct. Case 4 was a 38-year-old
woman with an unreliable VF who was referred for suspected glaucoma. Her GCT map
revealed a left homonymous vertical pattern of RGC loss, which may have been
related to a previous head trauma. CONCLUSIONS: Evaluation of the patterns of
macular RGC loss may be helpful in the differential diagnosis of RGC-related
diseases, including glaucoma and neurologic lesions. When a patient's VF is
unavailable, this method may be an effective tool for diagnosing and monitoring
transneuronal retrograde degeneration-related structural changes.
PMID- 25120342
TI - Patterns of subsequent progression of localized retinal nerve fiber layer defects
on red-free fundus photographs in normal-tension glaucoma.
AB - PURPOSE: To investigate patterns of subsequent progression of localized retinal
nerve fiber layer (RNFL) defects and to quantify the extent of progression in
normal-tension glaucoma (NTG) patients. METHODS: Thirty-three eyes of 33
consecutive NTG patients who had shown continuous progression of localized RNFL
defect on serial red-free fundus photographs were selected for the study.
Patterns of subsequent progression of localized RNFL defects were categorized,
and extents of progression were quantified. Serial evaluations of disc
stereophotographs and visual fields were also performed to detect progression.
RESULTS: The most common pattern was continuous widening of the defect towards
the macula (n = 11, 33.3%) followed by sharpening of the defect border after
widening of the defect towards the macula (n = 5, 15.2%), continuous widening of
the defect away from the macula (n = 2, 6.1%), and deepening of the defect after
appearance of a new defect (n = 2, 6.1%). Four eyes (12.1%) simultaneously showed
two patterns of subsequent progression. In 13 eyes that showed continuous
widening of the defect, subsequent angular widening towards the macula and away
from the macula were 9.2 +/- 6.0 degrees (range, 1.1 degrees to 24.4 degrees ;
n = 11) and 5.2 +/- 4.9 degrees (range, 0.3 degrees to 11.3 degrees ; n = 2),
respectively. Thirty-two eyes showed no progression of optic disc cupping. Out of
the 21 eyes in which Humphrey central 30-2 threshold visual field tests were
performed after progression of RNFL defects, 15 eyes showed no deterioration in
the visual field. CONCLUSIONS: There were nine patterns of subsequent progression
of localized RNFL defects. Among them, continuous RNFL loss proceeding temporally
was the most common one. Initial progression of the defect proceeded temporally,
especially in the defect located at the inferior fundus, might be at a risk of
further RNFL loss temporally.
PMID- 25120343
TI - Lateral geniculate body evoked potentials elicited by visual and electrical
stimulation.
AB - PURPOSE: Blind individuals who have photoreceptor loss are known to perceive
phosphenes with electrical stimulation of their remaining retinal ganglion cells.
We proposed that implantable lateral geniculate body (LGB) stimulus electrode
arrays could be used to generate phosphene vision. We attempted to refine the
basic reference of the electrical evoked potentials (EEPs) elicited by
microelectrical stimulations of the optic nerve, optic tract and LGB of a
domestic pig, and then compared it to visual evoked potentials (VEPs) elicited by
short-flash stimuli. METHODS: For visual function measurement, VEPs in response
to short-flash stimuli on the left eye of the domestic pig were assessed over the
visual cortex at position Oz with the reference electrode at Fz. After
anesthesia, linearly configured platinum wire electrodes were inserted into the
optic nerve, optic track and LGB. To determine the optimal stimulus current, EEPs
were recorded repeatedly with controlling the pulse and power. The threshold of
current and charge density to elicit EEPs at 0.3 ms pulse duration was about +/
10 uA. RESULTS: Our experimental results showed that visual cortex activity can
be effectively evoked by stimulation of the optic nerve, optic tract and LGB
using penetrating electrodes. The latency of P1 was more shortened as the
electrical stimulation was closer to LGB. The EEPs of two-channel in the visual
cortex demonstrated a similar pattern with stimulation of different spots of the
stimulating electrodes. We found that the LGB-stimulated EEP pattern was very
similar to the simultaneously generated VEP on the control side, although
implicit time deferred. CONCLUSIONS: EEPs and VEPs derived from visual-system
stimulation were compared. The LGB-stimulated EEP wave demonstrated a similar
pattern to the VEP waveform except implicit time, indicating prosthetic-based
electrical stimulation of the LGB could be utilized for the blind to perceive
vision of phosphenes.
PMID- 25120344
TI - Comparative quantification of plasma TDRD7 mRNA in cataract patients by real-time
polymerase chain reaction.
AB - PURPOSE: To investigate the relationship between plasma TDRD7 mRNA and lens
transparency, and to evaluate plasma TDRD7 mRNA as a potential marker for
cataracts and its sub-type by quantitatively analyzing human peripheral blood.
METHODS: Plasma RNA was extracted from 40 patients with cataracts, and 30 normal
controls of matched age and gender. Blood cholesterol and fasting glucose were
measured, and the RNA extracted from the sample was synthesized into cDNA. After
polymerase chain reaction, the results were compared after quantifying the TDRD7
mRNA using ABL1 mRNA for normalization. We analyzed the relative gene expression
data via the DeltaDeltaCt method. RESULTS: The normalized 2(-DeltaDeltaCt) of
plasma TDRD7 mRNA based on ABL1 mRNA was 1.52 +/- 0.63 in the case of the control
group and 1.05 +/- 0.34 in the case of the cataract patients, and the TDRD7
expression level of the cataract patients was lower than that of the control
group (p = 0.048). The comparison of the genetic values of different types of
cataracts demonstrated that the TDRD7 expression level of the cortical type and
mixed type were lower than those of the nuclear type and posterior subcapsular
opacity type (p = 0.017). CONCLUSIONS: Human cataracts and the TDRD7 gene loss-of
function mutations are strongly causally related, as the expression level of
plasma TDRD7 mRNA in patients with cataracts was statistically significantly
lower than in the normal control group.
PMID- 25120345
TI - Optical coherence tomography to evaluate dengue.
PMID- 25120346
TI - Is this really sutureless intrascleral pocket technique of transscleral fixation?
PMID- 25120347
TI - A Korean woman with reactive lymphoid hyperplasia of the uvea.
PMID- 25120348
TI - Pseudohypopyon after management of posterior capsule rupture using intracameral
triamcinolone injection in cataract surgery.
PMID- 25120349
TI - Accelerated versus conventional corneal collagen cross-linking in the treatment
of mild keratoconus: a comparative study.
AB - AIM: To evaluate the use of accelerated corneal collagen cross-linking in the
management of mild and moderate progressive keratoconus in comparison with
conventional cross-linking. PATIENTS AND METHODS: Prospective randomized
interventional case-control clinical trial. A total 25 eyes of 18 patients were
randomly divided into two groups: group A included 14 eyes that received
accelerated collagen cross-linking; and group B included eleven eyes that
received conventional cross-linking (Dresden protocol). Cases with grade 1 and 2
keratoconus (Krumeich classification) with topographic evidence of progression
were included. The uncorrected visual acuity and best spectacle-corrected visual
acuity were recorded. Pentacam((r)) corneal analysis imaging was used: The
maximum and minimum keratometry and the central corneal thickness were recorded.
Ocular Response Analyzer((r)) (ORA) measurements were carried out to document the
biomechanical parameters. Corneal hysteresis and corneal resistance factor were
recorded. Postoperative evaluation included uncorrected visual acuity, best
corrected visual acuity, and Pentacam and ORA measurements at 6 and 12 months.
The follow-up period was 12 months. RESULTS: A progressive decrease in the flat
keratometry, steep keratometry, and mean keratometry was noted throughout the
follow-up period in both the accelerated and conventional groups. The improvement
in keratometry was not statistically significant. The best spectacle-corrected
visual acuity showed a statistically significant improvement in both groups by 1
year. The corneal hysteresis and corneal resistance factor showed nonsignificant
improvement in both groups. The central corneal thickness showed a significant
thinning at 6 months in both groups but approached baseline values by 12 months.
CONCLUSION: Accelerated corneal collagen cross-linking appears to show comparable
results to conventional cross-linking in arresting the progression of mild
keratoconus.
PMID- 25120350
TI - Evaluation of dacryocystorhinostomy using optical coherence tomography and
rebamipide ophthalmic suspension.
AB - PURPOSE: To evaluate the surgical outcome of dacryocystorhinostomy (DCR) by
measuring the tear meniscus, using optical coherence tomography and rebamipide
ophthalmic suspension. METHODS: Patients with nasolacrimal obstruction and
chronic dacryocystitis who were scheduled for an endonasal DCR underwent tear
meniscus examinations before and 2 months after surgery. Vertical scans of the
inferior menisci were performed before and at 1, 3, 5, 7, and 10 minutes after
the instillation of rebamipide ophthalmic suspension. The tear menisci areas were
measured with imaging software. Ten young adults without epiphora formed the
control group. RESULTS: Anatomical success was achieved on 22 sides of 21
patients. The patients' postoperative tear menisci were significantly smaller
than the preoperative menisci at all points during the test, and the response to
volume loading in the postoperative patients was corrected to nearly that of the
young, healthy adults. Nevertheless, the postoperative meniscus area tended to be
larger than that of the young adults at all points. CONCLUSION: The reduced tear
meniscus area after DCR reflected the success of the surgical procedure. However,
incomplete recovery of the meniscus after the test might suggest a residual
disorder of the lacrimal drainage system after DCR.
PMID- 25120352
TI - Neuroretinitis in ocular bartonellosis: a case series.
AB - We report a case series of neuroretinitis in ocular bartonellosis and describe
the serologic verification for Bartonella henselae. This is a retrospective
interventional case series of four patients who presented in the ophthalmology
clinic of Hospital Universiti Sains Malaysia from June 2012 to March 2013. All
four patients had a history of contact with cats and had fever prior to ocular
symptoms. Each patient presented with neuroretinitis characterized by optic disc
swelling with macular star. Serology analysis showed strongly positive for B.
henselae in all of the patients. All patients were treated with oral azithromycin
(except case 4, who was treated with oral doxycycline), and two patients (case 1
and case 3) had poor vision at initial presentation that warranted the use of
oral prednisolone. All patients showed a good visual outcome except case 3.
Vision-threatening ocular manifestation of cat scratch disease can be improved
with systemic antibiotics and steroids.
PMID- 25120354
TI - Potential patient benefit of a subcutaneous formulation of tocilizumab for the
treatment of rheumatoid arthritis: a critical review.
AB - Treatment of rheumatoid arthritis (RA) was revolutionized during the last decade
with the development of new biologic disease-modifying anti-rheumatic drugs
(DMARDs) enabling the targeting of immune cells and cytokines other than tumor
necrosis factor (TNF). Subcutaneous formulations of the newer biologic DMARDs
facilitate not only patients' emancipation from the hospital, but reduce both
societal and medical costs. Intravenous tocilizumab (TCZ) in RA has an efficacy
and safety profile similar to anti-TNF in both the short and long-term. However,
TCZ can be administered in monotherapy without loss of efficacy when patients do
not tolerate methotrexate or synthetic DMARDs. TCZ is consistently found superior
to methotrexate and possibly superior to adalimumab in monotherapy in randomized
controlled trials. Subcutaneous administration of TCZ is as effective and safe as
its intravenous administration in RA patients during the first year of treatment.
Similar to intravenous TCZ, patients' weight and possibly previous use of anti
TNF influence the efficacy of subcutaneous TCZ. Additionally, combination with
synthetic DMARDs seems to expose RA patients to more adverse events independently
of its administration route. Pharmacokinetics of different administration routes
could potentially lead to differences in efficacy, adverse events, and auto
immunogenicity. The concentration of free TCZ before new TCZ dose (C trough) is
higher in the subcutaneous route, while the maximal concentration of free TCZ is
higher in the intravenous route. The subcutaneous dosages of TCZ 162 mg every
week, and every 2 weeks in RA patients with low body weight (<60 kg) work well.
Nevertheless, dosage and intervals of subcutaneous TCZ administration could be
adjusted during the course of treatment since 80% of non-Japanese RA patients
with usually higher body weight achieved similar efficacy with the low TCZ dosage
in combination with a synthetic DMARD. Patients want effective, easy-to
administer therapy with sustained prolonged efficacy without the need of
polypharmacy and with minimal to no side effects. Subcutaneous TCZ in RA patients
in monotherapy seems to live up to patients' expectations.
PMID- 25120353
TI - Design, synthesis, and anticancer activity of novel berberine derivatives
prepared via CuAAC "click" chemistry as potential anticancer agents.
AB - A series of novel derivatives of phenyl-substituted berberine triazolyls has been
designed and synthesized via copper-catalyzed azide-alkyne cycloaddition click
chemistry in an attempt to develop antitumor agents. All of the compounds were
evaluated for anticancer activity against a panel of three human cancer cell
lines, including MCF-7 (breast), SW-1990 (pancreatic), and SMMC-7721 (liver) and
the noncancerous human umbilical vein endothelial cell (HUVEC) cell lines. The
results indicated that most of the compounds displayed notable anticancer
activities against the MCF-7 cells compared with berberine. Among these
derivatives, compound 16 showed the most potent inhibitory activity against the
SW-1990 and SMMC-7721 cell lines, with half-maximal inhibitory concentration
(IC50) values of 8.54+/-1.97 MUM and 11.87+/-1.83 MUM, respectively. Compound 36
exhibited the most potent inhibitory activity against the MCF-7 cell line, with
an IC50 value of 12.57+/-1.96 MUM. Compound 16 and compound 36 exhibited low
cytotoxicity in the HUVEC cell line, with IC50 values of 25.49+/-3.24 MUM and
30.47+/-3.47 MUM. Furthermore, compounds 14, 15, 16, 17, 18, 32, and 36 exhibited
much better selectivity than berberine toward the normal cell line HUVEC.
PMID- 25120351
TI - Managing Sjogren's Syndrome and non-Sjogren Syndrome dry eye with anti
inflammatory therapy.
AB - Dry eye from Sjogren's syndrome is a multifactorial disease that results in
dysfunction of the lacrimal functional unit. Studies have shown changes in tear
composition, including inflammatory cytokines, chemokines, and metalloproteinase.
T-lymphocytes have been shown to increase in the conjunctiva and lacrimal glands
in patient and animal models. This inflammation is in part responsible for the
pathogenesis of the disease, which results in symptoms of eye irritation, ocular
surface epithelial disease, and loss of corneal barrier function. There are a
number of anti-inflammatory approaches for treating this disease. The current
study reviews details of immune response and anti-inflammatory therapies used to
control this disease.
PMID- 25120355
TI - Effects of annatto-derived tocotrienol supplementation on osteoporosis induced by
testosterone deficiency in rats.
AB - BACKGROUND: Previous animal models have demonstrated that tocotrienol is a
potential treatment for postmenopausal osteoporosis. This study evaluated the
antiosteoporotic effects of annatto-derived tocotrienol (AnTT) using a
testosterone-deficient osteoporotic rat model. METHODS: Forty rats were divided
randomly into baseline, sham, orchidectomized, AnTT, and testosterone groups. The
baseline group was euthanized without undergoing any surgical treatment or
intervention. The remaining groups underwent orchidectomy, with the exception of
the sham group. AnTT 60 mg/kg/day was given orally to the AnTT group, while the
testosterone group received testosterone enanthate 7 mg/kg per week
intramuscularly for 8 weeks. Structural changes in trabecular bone at the
proximal tibia were examined using microcomputed tomography. Structural and
dynamic changes at the distal femur were examined using histomorphometric
methods. Serum osteocalcin and C-terminal of type 1 collagen crosslinks were
measured. Bone-related gene expression in the distal femur was examined. RESULTS:
There were significant degenerative changes in structural indices in the
orchidectomized group (P<0.05), but no significant changes in dynamic indices,
bone remodeling markers, or gene expression (P>0.05) when compared with the sham
group. The AnTT group showed significant improvement in structural indices at the
femur (P<0.05) and significantly increased expression of bone formation genes
(P<0.05). Testosterone was more effective than AnTT in preventing degeneration of
bone structural indices in the femur and tibia (P<0.05). CONCLUSION: AnTT
supplementation improves bone health in testosterone-deficient rats by enhancing
bone formation. Its potential should be evaluated further by varying the dosage
and treatment duration.
PMID- 25120356
TI - The effects of Tai Ji Quan training on limits of stability in older adults.
AB - BACKGROUND: Limits of stability, defined as the ability to maintain the center of
gravity within the boundary of the base of support, is critically important for
older adults in performing their activities of daily living. However, few
exercise programs specifically tailored to enhance limits of stability exist. The
primary purpose of this study was to determine whether a therapeutically designed
intervention, Tai Ji Quan: Moving for Better Balance (TJQMBB), could improve
limits of stability in older adults. A secondary purpose was to examine
concomitant change in limits of stability and physical performance as a result of
the intervention. METHODS: A single-group design was used in which 145 community
dwelling older adults (average age: 75 years) were enrolled in TJQMBB classes,
participating twice weekly for 48 weeks. Primary outcome measures were three
indicators of limits of stability (LOS) (endpoint excursion, movement velocity,
and directional control), with secondary measures of physical performance being
Timed Up and Go and 50-foot speed walk (in seconds), which were assessed at
baseline, 24 weeks, and 48 weeks. Changes in the repeated measures of outcome
variables were analyzed via latent curve analysis. RESULTS: At 48 weeks, a
significant rate of change (improvement) over time was observed in the three
limits of stability indicators (endpoint execution: 8.30% LOS, P<0.001; movement
velocity: 0.86 degrees/second, P<0.001; directional control: 6.79% of 100,
P<0.001); all reached a threshold of real change as judged by the minimal
detectable change values. Improvements in the three limits of stability measures
were concomitantly correlated with improved (reduced times) performance scores in
the Timed Up and Go (-0.30, -0.45, and -0.55, respectively) and 50-foot walk (
0.33, -0.49, and -0.41, respectively). CONCLUSION: In this single-group study,
community-dwelling older adults trained through TJQMBB significantly improved
their limits of stability, providing preliminary support for the use of TJQMBB as
a therapeutic modality for enhancing functional activities in older adults.
PMID- 25120357
TI - Increased body fat rather than body weight has harmful effects on 4-year changes
of renal function in the general elderly population with a normal or mildly
impaired renal function.
AB - BACKGROUND: With increasing age, body fat increases and muscle mass reduces. Even
people with a normal weight may have a higher percentage of body fat. The aim of
this study is to investigate the association between increased body fat and renal
function decline (RFD) in the general elderly population with normal or mildly
impaired renal function. METHOD: We conducted a prospective study of 615 healthy
individuals in the general Korean population aged >= 60 years who participated in
two health screening check-ups separated by a 4-year period. Obesity was defined
as the highest sex-specific tertiles of the percentage body fat (PBF). The main
outcome was changes of estimated glomerular filtration rate (eGFR) during the 4
years. Significant RFD was defined as a decrease of eGFR over the upper quartile
(<=-2.1% per year). RESULTS: The mean age was 67.2 +/- 6.6 years. The median
value of the absolute decline in the eGFR and the percent change was -3.0
mL/minute/1.73 m(2) and -0.87%/year in men and -3.1 mL/minute/1.73 m(2) and
0.89%/year in women, respectively. When stratified by sex-specific PBF tertiles,
pronounced differences were observed in both sexes; those at the highest tertile
of PBF showed the greatest decline in eGFR. Even after adjustments for
traditional risk factors of RFD, PBF was independently associated with eGFR
changes (beta=-0.181; P<0.001). In addition, the harmful effect of a high PBF was
consistently found in subjects with a normal weight, too (beta=-0.141; P=0.006).
Cases of significant RFD occurred in 181 participants (29.4%), and the risk was
higher in obese participants as compared with the nonobese participants. The odd
ratios (95% confidence interval) for significant RFD were 2.76 (1.28-7.74) in men
and 2.02 (1.06-4.43) in women in a whole population and 3.15 (1.03-18.52) in men
and 1.44 (1.01-3.28) in women with a normal weight, respectively. CONCLUSION:
Among the elderly population without comorbidities, increased body fat has a
harmful effect on RFD, irrespective of body weight.
PMID- 25120358
TI - Age as a risk factor for acute mountain sickness upon rapid ascent to 3,700 m
among young adult Chinese men.
AB - BACKGROUND: The aim of this study was to explore the relationship between age and
acute mountain sickness (AMS) when subjects are exposed suddenly to high
altitude. METHODS: A total of 856 young adult men were recruited. Before and
after acute altitude exposure, the Athens Insomnia Scale score (AISS) was used to
evaluate the subjective sleep quality of subjects. AMS was assessed using the
Lake Louise scoring system. Heart rate (HR) and arterial oxygen saturation (SaO2)
were measured. RESULTS: Results showed that, at 500 m, AISS and insomnia
prevalence were higher in older individuals. After acute exposure to altitude,
the HR, AISS, and insomnia prevalence increased sharply, and the increase in
older individuals was more marked. The opposite trend was observed for SaO2. At
3,700 m, the prevalence of AMS increased with age, as did severe AMS, and AMS
symptoms (except gastrointestinal symptoms). Multivariate logistic regression
analysis showed that age was a risk factor for AMS (adjusted odds ratio [OR]
1.07, 95% confidence interval [CI] 1.01-1.13, P<0.05), as well as AISS (adjusted
OR 1.39, 95% CI 1.28-1.51, P<0.001). CONCLUSION: The present study is the first
to demonstrate that older age is an independent risk factor for AMS upon rapid
ascent to high altitude among young adult Chinese men, and pre-existing poor
subjective sleep quality may be a contributor to increased AMS prevalence in
older subjects.
PMID- 25120359
TI - The application of EDTA in drug delivery systems: doxorubicin liposomes loaded
via NH4EDTA gradient.
AB - The applications of ethylenediaminetetraacetic acid (EDTA) have been expanded
from the treatment of heavy metal poisoning to chelation therapies for
atherosclerosis, heart disease, and cancers, in which EDTA reduces morbidity and
mortality by chelating toxic metal ions. In this study, EDTA was used in a drug
delivery system by adopting an NH4EDTA gradient method to load doxorubicin into
liposomes with the goal of increasing therapeutic effects and decreasing drug
related cytotoxicity. The particle size of the optimum NH4EDTA gradient liposomes
was 79.4+/-1.87 nm, and the entrapment efficiency was 95.54%+/-0.59%. In vitro
studies revealed that liposomes prepared using an NH4EDTA gradient possessed long
term stability and delayed drug release. The in vivo studies also showed the
superiority of the new doxorubicin formulation. Compared with an equivalent drug
dose (5 mg/kg) prepared by (NH4)2SO4 gradient, NH4EDTA gradient liposomes showed
no significant differences in tumor inhibition ratio, but cardiotoxicity and
liposome-related immune organ damage were lower, and no drug-related deaths were
observed. These results show that use of the NH4EDTA gradient method to load
doxorubicin into liposomes could significantly reduce drug toxicity without
influencing antitumor activity.
PMID- 25120360
TI - Preparation, pharmacokinetics and biodistribution of baicalin-loaded liposomes.
AB - Baicalin (BA) is a major constituent of Scutellaria baicalensis Georgi, a
medicinal herb. Previous pharmacokinetic studies of BA showed its low oral
bioavailability. The aim of the present study was to develop a novel BA-loaded
liposome (BA-LP) to enhance oral bioavailability. BA-LP, composed of BA,
Tween((r)) 80, Phospholipon((r)) 90H, and citric acid at weight ratio of
96/50/96/50, respectively, was prepared by the effervescent dispersion technique
and characterized in terms of morphology, size, zeta potential, encapsulation
efficiency, and the in vitro release. Pharmacokinetics and biodistribution
studies were carried out in rats after oral administration of BA-LP and a
carboxymethyl cellulose suspension containing BA (BA-CMC) as a control. BA-LP
exhibited a spherical shape by transmission electron microscopy observation. BA
LP had a mean particle size of 373+/-15.5 nm, zeta potential of -20.1+/-0.22 mV,
and encapsulation efficiency of 82.7%+/-0.59%. The BA-LP showed a sustained
release behavior, and the in vitro drug-release kinetic model fit well with the
Weibull distribution equation: lnln (1/(1-Q)) =0.609 lnt -1.230 (r=0.995). The
oral bioavailability and the peak concentration of the BA-LP was threefold and
2.82-fold that of BA-CMC, respectively. The in vivo distribution results
indicated that drug concentrations were significantly increased in the liver,
kidney, and lung in the case of BA-LP, which were 5.59-fold, 2.33-fold, and 1.25
fold higher than those of BA-CMC, respectively. In conclusion, the study
suggested that BA-LP might be a potential oral drug delivery system to improve
bioavailability of BA.
PMID- 25120361
TI - Effects of size and surface of zinc oxide and aluminum-doped zinc oxide
nanoparticles on cell viability inferred by proteomic analyses.
AB - Although the health effects of zinc oxide nanoparticles (ZnONPs) on the
respiratory system have been reported, the fate, potential toxicity, and
mechanisms in biological cells of these particles, as related to particle size
and surface characteristics, have not been well elucidated. To determine the
physicochemical properties of ZnONPs that govern cytotoxicity, we investigated
the effects of size, electronic properties, zinc concentration, and pH on cell
viability using human alveolar-basal epithelial A549 cells as a model. We
observed that a 2-hour or longer exposure to ZnONPs induced changes in cell
viability. The alteration in cell viability was associated with the zeta
potentials and pH values of the ZnONPs. Proteomic profiling of A549 exposed to
ZnONPs for 2 and 4 hours was used to determine the biological mechanisms of ZnONP
toxicity. p53-pathway activation was the core mechanism regulating cell viability
in response to particle size. Activation of the Wnt and TGFbeta signaling
pathways was also important in the cellular response to ZnONPs of different
sizes. The cadherin and Wnt signaling pathways were important cellular mechanisms
triggered by surface differences. These results suggested that the size and
surface characteristics of ZnONPs might play an important role in their observed
cytotoxicity. This approach facilitates the design of more comprehensive systems
for the evaluation of nanoparticles.
PMID- 25120362
TI - Tolerance-like innate immunity and spleen injury: a novel discovery via the
weekly administrations and consecutive injections of PEGylated emulsions.
AB - There has been an increasing interest in the study of the innate immune system in
recent years. However, few studies have focused on whether innate immunity can
acquire tolerance. Therefore, in this study, we investigated tolerance in the
innate immune system via the consecutive weekly and daily injections of emulsions
modified with polyethylene glycol (PEG), referred to as PEGylated emulsions (PE).
The effects of these injections of PE on pharmacokinetics and biodistribution
were studied in normal and macrophage-depleted rats. Additionally, we evaluated
the antigenic specificity of immunologic tolerance. Immunologic tolerance against
PE developed after 21 days of consecutive daily injections or the fourth week of
PE administration. Compared with a single administration, it was observed that
the tolerant rats had a lower rate of PE clearance from the blood, which was
independent of the stress response. In addition, weekly PE injections caused
injury to the spleen. Furthermore, the rats tolerant to PEs with the methoxy
group (-OCH3) of PEG, failed to respond to the PEs with a different terminal
group of PEG or to non-PEG emulsions. Innate immunity tolerance was induced by
PE, regardless of the mode of administration. Further study of this mechanism
suggested that monocytes play an essential role in the suppression of innate
immunity. These findings provide novel insights into the understanding of the
innate immune system.
PMID- 25120363
TI - Development and characterization of magnetic iron oxide nanoparticles with a
cisplatin-bearing polymer coating for targeted drug delivery.
AB - A highly selective and efficient cancer therapy can be achieved using
magnetically directed superparamagnetic iron oxide nanoparticles (SPIONs) bearing
a sufficient amount of the therapeutic agent. In this project, SPIONs with a
dextran and cisplatin-bearing hyaluronic acid coating were successfully
synthesized as a novel cisplatin drug delivery system. Transmission electron
microscopy images as well as X-ray diffraction analysis showed that the
individual magnetite particles were around 4.5 nm in size and monocrystalline.
The small crystallite sizes led to the superparamagnetic behavior of the
particles, which was exemplified in their magnetization curves, acquired using
superconducting quantum interference device measurements. Hyaluronic acid was
bound to the initially dextran-coated SPIONs by esterification. The resulting
amide bond linkage was verified using Fourier transform infrared spectroscopy.
The additional polymer layer increased the vehicle size from 22 nm to 56 nm, with
a hyaluronic acid to dextran to magnetite weight ratio of 51:29:20. A maximum
payload of 330 MUg cisplatin/mL nanoparticle suspension was achieved, thus the
particle size was further increased to around 77 nm with a zeta potential of -45
mV. No signs of particle precipitation were observed over a period of at least 8
weeks. Analysis of drug-release kinetics using the dialysis tube method revealed
that these were driven by inverse ligand substitution and diffusion through the
polymer shell as well as enzymatic degradation of hyaluronic acid. The biological
activity of the particles was investigated in a nonadherent Jurkat cell line
using flow cytometry. Further, cell viability and proliferation was examined in
an adherent PC-3 cell line using xCELLigence analysis. Both tests demonstrated
that particles without cisplatin were biocompatible with these cells, whereas
particles with the drug induced apoptosis in a dose-dependent manner, with
secondary necrosis after prolonged incubation. In conclusion, combination of
dextran-coated SPIONs with hyaluronic acid and cisplatin represents a promising
approach for magnetic drug targeting in the treatment of cancer.
PMID- 25120364
TI - Examining the relationship between adherence and satisfaction with antidepressant
treatment.
AB - BACKGROUND: Adherence to antidepressant treatment is an essential step in the
management of patients with major depressive disorder, and several factors can
contribute to antidepressant nonadherence. Evidence supports the hypothesis that
patient treatment satisfaction will result in improved adherence; therefore, the
aim of this study was to investigate the relationship between patient treatment
satisfaction and adherence to antidepressants, and the role of patient beliefs
toward medication in patient treatment satisfaction. METHODS: This was an
observational, nonexperimental survey of all patients attending Al Amal
Psychiatric Hospital (500 beds) in Riyadh, Saudi Arabia. Medication adherence was
assessed using the eight-item Morisky Medication Adherence Scale (MMAS-8), and
treatment satisfaction was assessed using the Treatment Satisfaction
Questionnaire for Medication (TSQM 1.4). RESULTS: A total of 403 patients met the
inclusion criteria; 50.4% were females; participant age ranged from 18 to 60
years; and 16 % of the patients reported side effects after using
antidepressants. Both males and females reported high treatment satisfaction
rates: - 79.21% (standard deviation [SD] 8.52) and 86.55% (SD 14.34),
respectively - with statistically significant associations found for female sex,
older age, and three or more physician visits per year. Adherence to
antidepressants was associated with treatment satisfaction with the
antidepressants, with a direct positive correlation. CONCLUSION: The results of
this study showed high treatment satisfaction scores among patients in Saudi
Arabia with major depressive disorder, which correlated with adherence and
patient beliefs about the necessity of treatment. This finding has improved the
understanding of the role of patient beliefs, which can help caregivers and other
stakeholders to improve satisfaction with antidepressants.
PMID- 25120365
TI - A systematic review of randomized controlled trials of bupropion versus
methylphenidate in the treatment of attention-deficit/hyperactivity disorder.
AB - BACKGROUND: Some trials have suggested that bupropion, as well as
methylphenidate, is beneficial in the treatment of attention
deficit/hyperactivity disorder (ADHD). OBJECTIVES: The purpose of this systematic
review was to summarize the efficacy, acceptability, and tolerability of
bupropion in comparison with methylphenidate for ADHD treatment. Included studies
were randomized controlled trials (RCTs) that compared bupropion and
methylphenidate. Clinical studies conducted between January 1991 and January 2014
were reviewed. DATA SOURCES: MEDLINE((r)), EMBASETM, CINAHL, PsycINFO((r)), and
the Cochrane Controlled Trials Register were searched in January 2014.
Additionally, clinical trials were identified from the databases of
ClinicalTrials.gov and the EU Clinical Trials Register. STUDY ELIGIBLE CRITERIA
PARTICIPANTS AND INTERVENTIONS: All RCTs of bupropion and methylphenidate
reporting final outcomes relevant to 1) ADHD severity, 2) response or remission
rates, 3) overall discontinuation rate, or 4) discontinuation rate due to adverse
events. Language restriction was not applied. STUDY APPRAISAL AND SYNTHESIS
METHODS: The relevant clinical trials were examined and the data of interest were
extracted. Additionally, the risks of bias were also inspected. The efficacy
outcomes were the mean changed scores of ADHD rating scales, the overall response
rate, and the overall remission rates. The overall discontinuation rate and the
discontinuation rate due to adverse events were determined. Relative risks and
weighted mean differences or standardized mean differences with 95% confidence
intervals were estimated using a random effect model. RESULTS: A total of 146
subjects in four RCTs comparing bupropion with methylphenidate in the treatment
of ADHD were included. The pooled mean changed scores of the Iowa-Conner's
Abbreviated Parent and Teacher Questionnaires and the ADHD Rating Scale-IV for
parents and teachers of children and adolescents with ADHD in the bupropion- and
methylphenidate-treated groups were not significantly different. Additionally,
the pooled mean changed score in adult ADHD between the two groups, measured by
the ADHD Rating Scale-IV and the Adult ADHD Rating Scale, was also not
significantly different. The pooled rates of response, overall discontinuation,
and discontinuation due to adverse events between the two groups were not
significantly different. CONCLUSION: Based on limited data from this systematic
review, bupropion was as effective as methylphenidate for ADHD patients.
Additionally, tolerability and acceptability were also comparable. However, these
findings should be considered as very preliminary results. To confirm this
evidence, further studies in this area should be conducted.
PMID- 25120367
TI - Double-balloon tamponade in the management of postpartum hemorrhage: a case
series.
AB - To show the efficacy of double-balloon cervical ripening catheter in the
management of postpartum hemorrhage originating from the lower segment of the
uterus or the upper parts of the vagina. METHODS: Patients with intractable
bleeding from the lower segment of the uterus and the upper parts of the vagina
after Cesarean or vaginal deliveries were treated by double-balloon cervical
ripening catheter. RESULTS: Double-balloon catheter was used in seven patients,
and it was properly placed in all of them. No other intervention was needed to
control bleeding. Two patients were delivered vaginally, and five patients were
delivered by Cesarean section. Length of hospitalization was longer in the
vaginal delivery patients (average hospitalization was 12 days in the vaginal
delivery patients and 5 days in the Cesarean section patients). The need for
blood and blood products transfusion (average of blood and blood products
transfusion was 30 U in the vaginal delivery patients and 6 U in the Cesarean
patients) was also higher in the vaginal delivery patients. CONCLUSION: Although
double-balloon cervical ripening catheter is designed for the induction of labor,
it can successfully control intractable bleedings from the lower segment of the
uterus and the upper parts of the vagina. This procedure can save patients from
undergoing more morbid procedures.
PMID- 25120368
TI - Clinical utility of the neutrophil elastase inhibitor sivelestat for the
treatment of acute respiratory distress syndrome.
AB - Acute respiratory distress syndrome is a serious condition that can arise
following direct or indirect lung injury. It is heterogeneous and has a high
mortality rate. Supportive care is the mainstay of treatment and there is no
definitive pharmacological treatment as yet. Sivelestat is a neutrophil elastase
inhibitor approved in Japan and the Republic of Korea for acute lung injury,
including acute respiratory distress syndrome in patients with systemic
inflammatory response syndrome. The aim of this review is to examine the clinical
utility of sivelestat in different disease states, using data from nonclinical
and clinical studies. In nonclinical studies, sivelestat appears to show benefit
in acute lung injury without inhibiting the host immune defense in cases of
infection. Clinical studies do not yet provide a clear consensus. Phase III and
IV Japanese studies have shown improvements in pulmonary function, length of
intensive care unit stay, and mechanical ventilation, but a non-Japanese
multicenter study did not demonstrate sivelestat to have an effect on ventilator
free days or 28-day all-cause mortality. Evidence of improvement in various
parameters, including duration of stay in intensive care, mechanical ventilation,
the ratio of partial pressure of arterial oxygen and fraction of inspired oxygen
(PaO2/FIO2 ratio) ratio, and lung injury scores, has been shown in patients with
sepsis or gastric aspiration, and following the surgical treatment of esophageal
cancer. To date, there are no particular concerns regarding adverse events, and
the available data do not suggest that sivelestat might worsen infections. One
study has analyzed cost-effectiveness, finding that sivelestat may reduce costs
compared with standard care. The currently available evidence suggests that
sivelestat may show some benefit in the treatment of acute lung injury/acute
respiratory distress syndrome, although large, randomized controlled trials are
needed in specific pathophysiological conditions to explore these potential
benefits.
PMID- 25120369
TI - Impact of pharmacist interventions on drug-related problems and laboratory
markers in outpatients with human immunodeficiency virus infection.
AB - BACKGROUND: Substantial complexity has been introduced into treatment regimens
for patients with human immunodeficiency virus (HIV) infection. Many drug-related
problems (DRPs) are detected in these patients, such as low adherence,
therapeutic inefficacy, and safety issues. We evaluated the impact of pharmacist
interventions on CD4+ T-lymphocyte count, HIV viral load, and DRPs in patients
with HIV infection. METHODS: In this 18-month prospective controlled study, 90
outpatients were selected by convenience sampling from the Hospital Dia
University of Campinas Teaching Hospital (Brazil). Forty-five patients comprised
the pharmacist intervention group and 45 the control group; all patients had HIV
infection with or without acquired immunodeficiency syndrome. Pharmaceutical
appointments were conducted based on the Pharmacotherapy Workup method, although
DRPs and pharmacist intervention classifications were modified for applicability
to institutional service limitations and research requirements. Pharmacist
interventions were performed immediately after detection of DRPs. The main
outcome measures were DRPs, CD4+ T-lymphocyte count, and HIV viral load. RESULTS:
After pharmacist intervention, DRPs decreased from 5.2 (95% confidence interval
[CI] =4.1-6.2) to 4.2 (95% CI =3.3-5.1) per patient (P=0.043). A total of 122
pharmacist interventions were proposed, with an average of 2.7 interventions per
patient. All the pharmacist interventions were accepted by physicians, and among
patients, the interventions were well accepted during the appointments, but
compliance with the interventions was not measured. A statistically significant
increase in CD4+ T-lymphocyte count in the intervention group was found (260.7
cells/mm(3) [95% CI =175.8-345.6] to 312.0 cells/mm(3) [95% CI =23.5-40.6],
P=0.015), which was not observed in the control group. There was no statistical
difference between the groups regarding HIV viral load. CONCLUSION: This study
suggests that pharmacist interventions in patients with HIV infection can cause
an increase in CD4+ T-lymphocyte counts and a decrease in DRPs, demonstrating the
importance of an optimal pharmaceutical care plan.
PMID- 25120366
TI - Clinical and economic studies of eptifibatide in coronary stenting.
AB - Platelet adhesion and aggregation at the site of coronary stenting can have
catastrophic clinical and economic consequences. Therefore, effective platelet
inhibition is vital during and after percutaneous coronary intervention.
Eptifibatide is an intravenous antiplatelet agent that blocks the final common
pathway of platelet aggregation and thrombus formation by binding to glycoprotein
IIb/IIIa receptors on the surface of platelets. In clinical studies, eptifibatide
was associated with a significant reduction of mortality, myocardial infarction,
or target vessel revascularization in patients with acute coronary syndrome
undergoing percutaneous coronary intervention. However, recent trials conducted
in the era of dual antiplatelet therapy and newer anticoagulants failed to
demonstrate similar results. The previously seen favorable benefit of
eptifibatide was mainly offset by the increased risk of bleeding. Current
American College of Cardiology/American Heart Association guidelines recommend
its use as an adjunct in high-risk patients who are undergoing percutaneous
coronary intervention with traditional anticoagulants (heparin or enoxaparin),
who are not otherwise at high risk of bleeding. In patients receiving bivalirudin
(a newer safer anticoagulant), routine use of eptifibatide is discouraged except
in select situations (eg, angiographic complications). Although older
pharmacoeconomic studies favor eptifibatide, in the current era of P2Y12
inhibitors and newer safer anticoagulants, the increased costs associated with
bleeding make the routine use of eptifibatide an economically nonviable option.
The cost-effectiveness of eptifibatide with the use of strategies that decrease
the bleeding risk (eg, transradial access) is unknown. This review provides an
overview of key clinical and economic studies of eptifibatide well into the
current era of potent antiplatelet agents, novel safer anticoagulants, and
contemporary percutaneous coronary intervention.
PMID- 25120370
TI - The difficulties of interprofessional teamwork in diabetes care: a questionnaire
survey.
AB - BACKGROUND: Diabetes is a multifactorial disease and its nature means that
interprofessional teamwork is essential for its treatment. However, in general,
interprofessional teamwork has certain problems that impede its function. To
clarify these problems in relation to diabetes care, a questionnaire survey was
conducted. METHODS: The participants who were involved in diabetes-related
educational seminars, and medical personnel who were engaged in diabetes care
from the National Center for Global Health and Medicine, were asked to complete
the questionnaire about perceptions of, and satisfaction with, interprofessional
teamwork across multiple health care providers, who were actually involved in
diabetes care. RESULTS: From 456 people who were asked to take the questionnaire,
275 people answered. The percentages of the respondents according to profession
who considered multidisciplinary teamwork sufficient were as follows: physicians,
20.5%; nurses, 12.7%; registered dietitians, 29.6%; pharmacists, 21.9%;
physiotherapists, 18.2%; and clinical laboratory technicians 15.4%. Insufficient
interprofessional communication and inconsistency in motivation levels among
staff were frequently cited as causes of insufficient teamwork. All professions
considered interprofessional meetings or conferences necessary and essential for
teamwork. CONCLUSION: The survey revealed that interprofessional teamwork in
diabetes care is currently insufficient. Continuous efforts to change each
profession's perceptions about interprofessional teamwork and efforts to improve
the quality of interprofessional meetings are necessary.
PMID- 25120371
TI - Silencing B7-H1 enhances the anti-tumor effect of bladder cancer antigen-loaded
dendritic cell vaccine in vitro.
AB - OBJECTIVE: The aim of this study was to examine whether short hairpin RNA (shRNA)
expressing lentiviral particles targeting B7-H1 infection could result in B7-H1
knockdown on dendritic cells (DCs) and to investigate whether B7-H1 silencing
could augment the immune function of DCs and further elicit a more potent anti
tumor immune effect against bladder cancer cells in vitro. METHODS: Monocyte
derived DCs, which were generated from peripheral blood mononuclear cells, were
infected by a recombinant lentivirus containing shRNA sequence aimed at B7-H1.
After that, the infected DCs were pulsed by tumor antigens and used to stimulate
cytotoxic T lymphocytes-based anti-tumor effect in vitro. RESULTS: The lentivirus
mediated shRNA delivery method efficiently and effectively silenced B7-H1 in DCs.
Furthermore, the B7-H1 silencing enhanced the stimulatory capacity and the
secretion of interleukin-12, but down-regulated interleukin-10 secretion. And
more importantly, the anti-tumor effect of bladder cancer antigen-loaded DC
vaccine in vitro was also potentially augmented. CONCLUSION: This study suggests
that a combination of B7-H1 knockdown and target antigen delivery could augment
anti-tumor effects in vitro, which potentially provides a novel strategy in the
immunotherapy of bladder cancer.
PMID- 25120372
TI - PKN1 modulates TGFbeta and EGF signaling in HEC-1-A endometrial cancer cell line.
AB - BACKGROUND: The response of cells to TGFbeta and EGF is mediated by a network of
various intracellular regulators. The signaling crosstalk between different
regulators is of key importance for tumorigenesis. The crosstalk may explain the
modulation of cellular responses to the same regulator by another signaling
molecule. As PKN1 - a serine/threonine kinase implicated in tumorigenesis - was
identified as potential crosstalk node for TGFbeta and EGF signaling, the
cellular functions that may be affected by PKN1 in a crosstalk of TGFbeta and EGF
were explored. METHODS: To investigate the contribution of PKN1 to TGFbeta and
EGF signaling, transiently PKN1-transfected HEC-1-A endometrial cancer cells were
generated and subjected to treatment with TGFbeta1, EGF, and their combination.
Proliferation, apoptosis, invasion, wound healing, and migration assays were
performed. The impact of PKN1 on the expression and phosphorylation of
intracellular proteins was monitored by immunoblotting. RESULTS: It was
demonstrated that PKN1 modulated the responses of HEC-A-1 endometrial cancer
cells to TGFbeta1 and EGF. PKN1 had an inhibitory effect on the stimulation of
cell migration, and PKN1 kinase activity was required for the inhibitory effect
of TGFbeta and EGF on cell proliferation and invasiveness. It was observed that
phosphorylation of Smad2, FAK, and Erk1/2 correlated with responses of the cells
to TGFbeta1 and EGF. CONCLUSION: PKN1 modulates TGFbeta- and EGF-dependent
regulation of cell proliferation, migration, and invasiveness, and therefore is a
component of the network signaling downstream of TGFbeta and EGF.
PMID- 25120373
TI - A community-based exercise intervention transitions metabolically abnormal obese
adults to a metabolically healthy obese phenotype.
AB - BACKGROUND: Lower habitual physical activity and poor cardiorespiratory fitness
are common features of the metabolically abnormal obese (MAO) phenotype that
contribute to increased cardiovascular disease risk. The aims of the present
study were to determine 1) whether community-based exercise training transitions
MAO adults to metabolically healthy, and 2) whether the odds of transition to
metabolically healthy were larger for obese individuals who performed higher
volumes of exercise and/or experienced greater increases in fitness. METHODS AND
RESULTS: Metabolic syndrome components were measured in 332 adults (190 women,
142 men) before and after a supervised 14-week community-based exercise program
designed to reduce cardiometabolic risk factors. Obese (body mass index >=30 kg .
m(2)) adults with two to four metabolic syndrome components were classified as
MAO, whereas those with no or one component were classified as metabolically
healthy but obese (MHO). After community exercise, 27/68 (40%) MAO individuals
(P<0.05) transitioned to metabolically healthy, increasing the total number of
MHO persons by 73% (from 37 to 64). Compared with the lowest quartiles of
relative energy expenditure and change in fitness, participants in the highest
quartiles were 11.6 (95% confidence interval: 2.1-65.4; P<0.05) and 7.5 (95%
confidence interval: 1.5-37.5; P<0.05) times more likely to transition from MAO
to MHO, respectively. CONCLUSION: Community-based exercise transitions MAO adults
to metabolically healthy. MAO adults who engaged in higher volumes of exercise
and experienced the greatest increase in fitness were significantly more likely
to become metabolically healthy. Community exercise may be an effective model for
primary prevention of cardiovascular disease.
PMID- 25120374
TI - Diabetes disease progression in Goto-Kakizaki rats: effects of salsalate
treatment.
AB - This study investigates the antidiabetic effects of salsalate on disease
progression of diabetes in non-obese diabetic Goto-Kakizaki (GK) rats, an
experimental model of type 2 diabetes. Salsalate was formulated in rat chow
(1,000 ppm) and used to feed rats from 5 to 21 weeks of age. At 5 weeks of age,
GK and Wistar (WIS) control rats were subdivided into four groups, each composed
of six rats: GK rats with standard diet (GK-C); GK rats with salsalate-containing
diet (GK-S); WIS rats with standard diet (WIS-C); and WIS rats with salsalate
containing diet (WIS-S). The GK-C rats (167.2+/-11.6 mg/dL) showed higher blood
glucose concentrations than WIS-C rats (133.7+/-4.9 mg/dL, P<0.001) at the
beginning of the experiment, and had substantially elevated blood glucose from an
age of 15 weeks until sacrifice at 21 weeks (341.0+/-133.6 mg/dL). The GK-S rats
showed an almost flat profile of blood glucose from 4 weeks (165.1+/-11.0 mg/dL)
until sacrifice at 21 weeks of age (203.7+/-22.2 mg/dL). While this difference in
blood glucose between 4 and 21 weeks in GK-S animals was significant, blood
glucose at 21 weeks was significantly lower in GK-S compared to GK-C animals. At
sacrifice, salsalate decreased plasma insulin (GK-S =1.0+/-0.3; GK-C =2.0+/-0.3
ng/mL, P<0.001) and increased plasma adiponectin concentrations (GK-S =15.9+/
0.7; GK-C =9.7+/-2.0 MUg/mL, P<0.001). Salsalate also lowered total cholesterol
in GK-S rats (96.1+/-8.5 mg/dL) compared with GK-C rats (128.0+/-11.4 mg/dL,
P<0.001). Inflammation-related genes (Ifit1 and Iigp1) exhibited much higher mRNA
expression in GK-C rats than WIS-C rats in liver, adipose, and muscle tissues,
while salsalate decreased the Ifit1 and Iigp1 mRNA only in adipose tissue. These
results suggest that salsalate acts to both increase adiponectin and decrease
adipose tissue-based inflammation while preventing type 2 diabetes disease
progression in GK rats.
PMID- 25120375
TI - Transdermal fentanyl patch for postoperative analgesia in total knee
arthroplasty: a randomized double-blind controlled trial.
AB - PURPOSE: To assess the efficacy of a transdermal fentanyl patch (TFP) (50
MUg/hour) applied 10-12 hours before surgery versus placebo for postoperative
pain control of total knee arthroplasty (TKA). MATERIALS AND METHODS: We enrolled
40 patients undergoing elective TKA under spinal anesthesia using isobaric or
hyperbaric bupivacaine. Subjects were randomized to receive a TFP (Duragesic((r))
50 MUg/hour) or placebo patch applied with a self-adhesive to the anterior chest
wall 10-12 hours before spinal anesthesia. Every patient was given patient
controlled morphine for postoperative pain control. Patients were evaluated every
4 hours until 48 hours. RESULTS: Morphine consumption at 24 and 48 hours in the
TFP group versus the placebo group was 15.40+/-12.65 and 24.90+/-20.11 mg versus
33.60+/-19.06 and 57.80+/-12.65 mg (P<=0.001). Numeric rating scale scores at
rest and during movement over 48 hours were lower in the TFP group. Ambulation
and nausea/vomiting scores were statistically greater, but not clinically
significant in the TFP group. Sedation scores were low and not statistically
significantly different between groups. There was no severe respiratory
depression. CONCLUSION: TFP (50 MUg/hour) applied 10-12 hours before surgery can
effectively and safely decrease morphine consumption and pain scores during the
first 48 hours after TKA surgery.
PMID- 25120378
TI - "One for all and all for one": consensus-building within communities in rural
India on their health microinsurance package.
AB - INTRODUCTION: This study deals with consensus by poor persons in the informal
sector in rural India on the benefit-package of their community-based health
insurance (CBHI). In this article we describe the process of involving rural poor
in benefit-package design and assess the underlying reasons for choices they made
and their ability to reach group consensus. METHODS: The benefit-package
selection process entailed four steps: narrowing down the options by community
representatives, plus three Choosing Healthplans All Together (CHAT) rounds
conducted among female members of self-help groups. We use mixed-methods and four
sources of data: baseline study, CHAT exercises, in-depth interviews, and
evaluation questionnaires. We define consensus as a community resolution reached
by discussion, considering all opinions, and to which everyone agrees. We use the
coefficient of unalikeability to express consensus quantitatively (as variability
of categorical variables) rather than just categorically (as a binomial Yes/No).
FINDINGS: The coefficient of unalikeability decreased consistently over
consecutive CHAT rounds, reaching zero (ie, 100% consensus) in two locations, and
confirmed gradual adoption of consensus. Evaluation interviews revealed that the
wish to be part of a consensus was dominant in all locations. The in-depth
interviews indicated that people enjoyed the participatory deliberations, were
satisfied with the selection, and that group decisions reflected a consensus
rather than majority. Moreover, evidence suggests that pre-selectors and
communities aimed to enhance the likelihood that many households would benefit
from CBHI. CONCLUSION: The voluntary and contributory CBHI relies on an engaging
experience with others to validate perceived priorities of the target group. The
strongest motive for choice was the wish to join a consensus (more than price or
package-composition) and the intention that many members should benefit. The
degree of consensus improved with iterative CHAT rounds. Harnessing group
consensus requires catalytic intervention, as the process is not spontaneous.
PMID- 25120377
TI - Spiritual and religious aspects of skin and skin disorders.
AB - Skin and skin disorders have had spiritual aspects since ancient times. Skin,
hair, and nails are visible to self and others, and touchable by self and others.
The skin is a major sensory organ. Skin also expresses emotions detectable by
others through pallor, coldness, "goose bumps", redness, warmth, or sweating.
Spiritual and religious significances of skin are revealed through how much of
the skin has been and continues to be covered with what types of coverings, scalp
and beard hair cutting, shaving and styling, skin, nail, and hair coloring and
decorating, tattooing, and intentional scarring of skin. Persons with visible
skin disorders have often been stigmatized or even treated as outcasts. Shamans
and other spiritual and religious healers have brought about healing of skin
disorders through spiritual means. Spiritual and religious interactions with
various skin disorders such as psoriasis, leprosy, and vitiligo are discussed.
Religious aspects of skin and skin diseases are evaluated for several major
religions, with a special focus on Judaism, both conventional and kabbalistic.
PMID- 25120379
TI - Empathy levels among first year Malaysian medical students: an observational
study.
PMID- 25120376
TI - Noncontraceptive benefits of the estradiol valerate/dienogest combined oral
contraceptive: a review of the literature.
AB - Combined oral contraceptives formulated to include estradiol (E2) have recently
become available for the indication of pregnancy prevention. A combined estradiol
valerate and dienogest pill (E2V/DNG), designed to be administered using an
estrogen step-down and a progestin step-up regimen over 26 days of active
treatment followed by 2 days of placebo (26/2-day regimen), has also undergone
research to assess the potential for additional noncontraceptive benefits.
Randomized, placebo-controlled studies have demonstrated that E2V/DNG is an
effective treatment for heavy menstrual bleeding - a reduction in median
menstrual blood loss approaching 90% occurs after 6 months of treatment. To date,
E2V/DNG is the only oral contraceptive approved for this indication. Comparator
studies have also demonstrated a reduction in hormone withdrawal-associated
symptoms in users of E2V/DNG compared with a conventional 21/7-day regimen of
ethinylestradiol/levonorgestrel. Other potential noncontraceptive benefits
associated with E2V/DNG, like improvement in dysmenorrhea, sexual function, and
quality of life, are comparable with those associated with other combined oral
contraceptives and are discussed further in this review.
PMID- 25120380
TI - Primary healthcare system and practice characteristics in Singapore.
AB - It is crucial to adapt and improve the (primary) health care systems of countries
to prepare for future patient profiles and their related needs. The main aim of
this study was to acquire a comprehensive overview of the perceptions of primary
care experts in Singapore about the state of primary care in Singapore, and to
compare this with the state of primary care in other countries. Notwithstanding
ranked 2(nd) in terms of efficiency of health care, Singapore is facing
significant health care challenges. Emails were sent to 85 experts, where they
were asked to rate Singapore's primary care system based on nine internationally
adopted health system characteristics and six practice characteristics (response
rate = 29%). The primary care system in Singapore received an average of 10.9 out
of 30 possible points. Lowest ratings were given to: earnings of primary care
physicians compared to specialists, requirement for 24 hr accessibility of
primary care services, standard of family medicine in academic departments,
reflection of community served by practices in patient lists, and the access to
specialists without needing to be referred by primary care physicians. Singapore
was categorized as a 'low' primary care country according to the experts.
PMID- 25120381
TI - An exploration of self-management support in the context of palliative nursing: a
modified concept analysis.
AB - BACKGROUND: The role of self-management is often ambiguous, yet, it is an
important area in clinical practice for palliative nurses. A clear conceptual
understanding, however, of what it represents is lacking. METHOD: This paper
reports an analysis of the concept of self-management support in palliative
nursing. Avant and Walker's method was used to guide this concept analysis. A
search of electronic databases (1990-2013), use of internet search engines and
supplementary hand searching produced an international data set of reviews,
empirical research, editorials, protocols and guidelines. RESULTS: Based on the
analysis self-management support in palliative nursing has been defined as
assessing, planning, and implementing appropriate care to enable the patient to
live until they die and supporting the patient to be given the means to master or
deal with their illness or their effects of their illness themselves.
CONCLUSIONS: Clarity with the concept of self-management support and palliative
nursing could enable nurses to provide more patient and family centred care to
people facing life threatening illnesses.
PMID- 25120382
TI - Metformin inhibition of neuroblastoma cell proliferation is differently modulated
by cell differentiation induced by retinoic acid or overexpression of NDM29 non
coding RNA.
AB - BACKGROUND: Metformin is a widely used oral hypoglycemizing agent recently
proposed as potential anti-cancer drug. In this study we report the
antiproliferative effect of metformin treatment in a high risk neuroblastoma cell
model, focusing on possible effects associated to different levels of
differentiation and/or tumor initiating potential. METHODS: Antiproliferative and
cytotoxic effects of metformin were tested in human SKNBE2 and SH-SY5Y
neuroblastoma cell lines and in SKNBE2 cells in which differentiation is induced
by retinoic acid treatment or stable overexpression of NDM29 non-coding RNA, both
conditions characterized by a neuron-like differentiated phenotype. RESULTS: We
found that metformin significantly inhibits the proliferation of NB cells, an
effect that correlates with the inhibition of Akt, while AMPK activity resulted
unchanged. Notably, metformin effects were modulated in a different ways by
differentiating stimuli, being abolished after retinoic acid treatment but
potentiated by overexpression of NDM29. CONCLUSION: These data suggest the
efficacy of metformin as neuroblastoma anticancer agent, and support the
requirement of further studies on the possible role of the differentiation status
on the antiproliferative effects of this drug.
PMID- 25120385
TI - The in-hospital consultation today: whom does it best serve?
PMID- 25120383
TI - New strategy to control cell migration and metastasis regulated by CCN2/CTGF.
AB - Connective tissue growth factor (CTGF)/CCN family member 2 (CCN2) is a CCN family
member of matricellular signaling modulators. It has been shown that CCN2/CTGF
mediates cell adhesion, aggregation and migration in a large variety of cell
types, including vascular endothelial cells, fibroblasts, epithelial cells,
aortic smooth muscle and also pluripotent stem cells. Others matricellular
proteins are capable of interacting with CCN2/CTGF to mediate its function. Cell
migration is a key feature for tumor cell invasion and metastasis. CCN2/CTGF
seems to be a prognostic marker for cancer. In addition, here we intend to
discuss recent discoveries and a new strategy to develop therapies against
CCN2/CTGF, in order to treat cancer metastasis.
PMID- 25120386
TI - The man in the waiting room.
PMID- 25120384
TI - hsa-mir-30c promotes the invasive phenotype of metastatic breast cancer cells by
targeting NOV/CCN3.
AB - BACKGROUND: For treatment and prevention of metastatic disease, one of the
premier challenges is the identification of pathways and proteins to target for
clinical intervention. Micro RNAs (miRNAs) are short, non-coding RNAs, which
regulate cellular activities by either mRNA degradation or translational
inhibition. Our studies focused on the invasive properties of hsa-mir30c based on
its high expression in MDA-MB-231 metastatic cells and our bioinformatic analysis
of the Cancer Genome Atlas that identified aberrant hsa-mir-30c to be associated
with poor survival. METHODS: Contributions of hsa-mir-30c to breast cancer cell
invasion were examined by Matrigel invasion transwell assays following modulation
of hsa-mir-30c or hsa-mir-30c* levels in MDA-MB-231 cells. hsa-mir-30c in silico
predicted targets linked to cell invasion were screened for targeting by hsa-mir
30c in metastatic breast cancer cells by RT-qPCR. The contribution to invasion by
a target of hsa-mir-30c, Nephroblastoma overexpressed (NOV), was characterized by
siRNA and invasion assays. Significant effects were determined using Student's T
tests with Welch's correction for unequal variance. RESULTS: MCF-7 and MDA-MB-231
cells were used as models of poorly invasive and late-stage metastatic disease,
respectively. By modulating the levels of hsa-mir-30c in these cells, we observed
concomitant changes in breast cancer cell invasiveness. From predicted targets of
hsa-mir-30c that were related to cellular migration and invasion, NOV/CCN3 was
identified as a novel target of hsa-mir-30c. Depleting NOV by siRNA caused a
significant increase in the invasiveness of MDA-MB-231 cells is a regulatory
protein associated with the extracellular matrix. CONCLUSIONS: NOV/CCN3
expression, which protects cells from invasion, is known in patient tumors to
inversely correlate with advanced breast cancer and metastasis. This study has
identified a novel target of hsa-mir-30c, NOV, which is an inhibitor of the
invasiveness of metastatic breast cancer cells. Thus, hsa-mir-30c-mediated
inhibition of NOV levels promotes the invasive phenotype of MDA-MB-231 cells and
significantly, the miR-30/NOV pathways is independent of RUNX2, a known target of
hsa-mir-30c that promotes osteolytic disease in metastatic breast cancer cells.
Our findings allow for mechanistic insight into the clinical observation of poor
survival of patients with elevated hsa-mir-30c levels, which can be considered
for miRNA-based translational studies.
PMID- 25120387
TI - Percutaneous closure versus medical therapy alone for cryptogenic stroke patients
with a patent foramen ovale: meta-analysis of randomized controlled trials.
AB - Of cryptogenic stroke patients younger than 55 years of age, up to 61% have had a
patent foramen ovale (PFO). Observational studies have revealed reductions in
recurrent neurologic events through PFO closure versus medical therapy, and
randomized controlled trials have shown nonsignificant trends toward benefit. We
systematically searched for randomized controlled trials of percutaneous PFO
closure with medical therapy versus medical therapy alone in patients with
cryptogenic stroke and performed a meta-analysis of treatment outcomes. The
primary endpoint was combined death, stroke, and transient ischemic attack. We
included 3 trials. Of 2,303 total patients, 1,150 underwent PFO closure and 1,153
received medical therapy (median follow-up period, 2.6 yr). The pooled incidence
of the primary endpoint was 1.2 events per 100 patient-years in the closure group
(95% confidence interval [CI], 0.2-2.3) and 1.8 in the therapy group (95% CI, 0.7
2.9) (P=0.32); the number needed to treat was 167 (range, 100-500). The
corresponding pooled hazard ratio was 0.67 (95% CI, 0.44-1.01; P=0.054) in favor
of closure. Closure was associated with an increased risk of atrial fibrillation:
relative risk=3.51 (95% CI, 1.44-8.55; P=0.006). When stratified by device, use
of the AmplatzerTM PFO Occluder resulted in significant stroke-prevention benefit
over medical therapy alone: hazard ratio=0.44 (95% CI, 0.21-0.95; P=0.037). When
compared with medical therapy alone, PFO closure with medical therapy showed a
trend toward a decreased hazard of combined events, although the absolute event
reduction was small and the number needed to treat was high.
PMID- 25120388
TI - Abdominal fat suspension device for maintaining normal cardiorespiratory function
in patients undergoing conscious sedation during surgery: a feasibility study.
AB - Obese patients undergoing conscious-sedation surgery have increased perioperative
morbidity because their excess abdominal tissue limits diaphragmatic excursion.
We describe a simple device that might help attenuate this risk. We created a
noninvasive suction device for abdominal suspension. By lifting the burden of
excess weight, this device should decrease respiratory effort. To test the
feasibility of excess weight removal in relieving cardiac stress, we tested 22
supine, healthy, normal-weight subjects by measuring their heart rates with and
without a 13-kg tissue model on their abdomen to simulate excess weight. There
was no significant difference in blood oxygen saturation before and after weight
removal (P=0.318). However, the decrease in heart rate was significant (P
<0.0001; paired 2-sample, one-tailed t test), which implies decreased respiratory
effort. This result suggests the possibility that abdominal mass suspension in
obese patients is associated with decreased respiratory effort.
PMID- 25120389
TI - Use of oversized injectable valves in growing children for total repair of right
ventricular outflow tract anomalies (preliminary results).
AB - Right ventricular outflow tract surgery was originally confined to transannular
patching, in the belief that pulmonary regurgitation was well tolerated. Because
follow-up evaluations revealed the deleterious effects of pulmonary
regurgitation, surgery today aims to spare or replace the valve. Available
replacement devices have short lifetimes, considering growth mismatch in
children. We hypothesize that oversizing the right infundibulum anticipates
growth and that a squeezed prosthesis can complete the expansion process. The No
React(r) Injectable BioPulmonic Valve is designed for right infundibular surgery
in adults, and hundreds of implants have shown promising results. We used this
device for surgery in babies, with the addition of an innovative oversizing
technique. This study evaluates our preliminary results and investigates whether
such a technique might reduce growth mismatch. From September 2010 through July
2012, we implanted 11 injectable pulmonic valves. The median age of our patients
was 23 months. After opening the right infundibulum, we enlarged it as much as
possible with a wide patch. Before completing the patch suture, we injected an
oversized valve. No problems occurred during surgery. No major insufficiency or
leak was observed. We conclude that prostheses can be quite oversized and perform
well even when not completely expanded. Oversized injectable pulmonic valves,
shrunken to a smaller diameter, enabled the implantation of a device wider than
otherwise possible, without affecting performance. Moreover, the prosthesis
tended to return to its original size following growth, thereby reducing growth
mismatch. Longer follow-up and larger numbers of patients are needed for
verification.
PMID- 25120390
TI - Left ventricular remodeling after late revascularization correlates with baseline
viability.
AB - The ideal management of stable patients who present late after acute ST-elevation
myocardial infarction (STEMI) is still a matter of conjecture. We hypothesized
that the extent of improvement in left ventricular function after successful
revascularization in this subset was related to the magnitude of viability in the
infarct-related artery territory. However, few studies correlate the improvement
of left ventricular function with the magnitude of residual viability in patients
who undergo percutaneous coronary intervention in this setting. In 68 patients
who presented later than 24 hours after a confirmed first STEMI, we performed
resting, nitroglycerin-enhanced, technetium-99m sestamibi single-photon emission
computed tomography-myocardial perfusion imaging (SPECT-MPI) before percutaneous
coronary intervention, and again 6 months afterwards. Patients whose baseline
viable myocardium in the infarct-related artery territory was more than 50%, 20%
to 50%, and less than 20% were divided into Groups 1, 2, and 3 (mildly,
moderately, and severely reduced viability, respectively). At follow-up, there
was significant improvement in end-diastolic volume, end-systolic volume, and
left ventricular ejection fraction in Groups 1 and 2, but not in Group 3. We
conclude that even late revascularization of the infarct-related artery yields
significant improvement in left ventricular remodeling. In patients with more
than 20% viable myocardium in the infarct-related artery territory, the extent of
improvement in left ventricular function depends upon the amount of viable
myocardium present. The SPECT-MPI can be used as a guide for choosing patients
for revascularization.
PMID- 25120391
TI - Heart failure in remission for more than 13 years after removal of a left
ventricular assist device.
AB - Mechanical cardiac unloading with use of a left ventricular assist device (LVAD)
is associated with substantial improvements in left ventricular function and
enables subsequent LVAD explantation in some patients. We describe the case of a
35-year-old man with dilated nonischemic cardiomyopathy who was supported with an
LVAD for 9 months. After the device was removed, he led a normal life for 13
years and 4 months. However, at 49 years of age, he presented with new signs and
symptoms of heart failure, necessitating implantation of a 2nd LVAD. Afterwards,
he has remained asymptomatic. This case is unique in that the patient lived a
normal life for longer than a decade before renewed left ventricular
decompensation necessitated repeat LVAD therapy. Histologic examination revealed
few changes between the first device's removal in 1999 and the 2nd device's
implantation in 2012.
PMID- 25120392
TI - Myxoma of the left ventricle.
AB - This report concerns a 69-year-old woman who presented with an asymptomatic
myxoma in the left ventricle. The tumor was successfully excised. We provide a
very brief review of 72 other published cases of surgically treated left
ventricular myxoma.
PMID- 25120393
TI - Nontyphoidal cardiac salmonellosis: two case reports and a review of the
literature.
AB - Nontyphoidal Salmonella, especially Salmonella enterica, is a rare cause of
endocarditis and pericarditis that carries a high mortality rate. Proposed
predisposing conditions include immunodeficiency states, congenital heart
defects, and cardiac valve diseases. We present 2 cases of cardiovascular
salmonellosis. The first case is that of a 73-year-old woman with mechanical
mitral and bioprosthetic aortic valves who died from sequelae of nontyphoidal
Salmonella mitral valve vegetation, aortic valve abscess, and sepsis. The second
case is that of a 62-year-old man with a recent systemic lupus erythematosus
exacerbation treated with oral steroids, who presented with obstructive features
of tamponade and sepsis secondary to a large S. enteritidis purulent pericardial
cyst. He recovered after emergent pericardial drainage and antibiotic therapy.
Identifying patients at risk of cardiovascular salmonellosis is important for
early diagnosis and treatment to minimize sequelae and death. We reviewed the
literature to identify the predisposing risk factors of nontyphoidal Salmonella
cardiac infection.
PMID- 25120394
TI - Left ventricular aneurysm repair with use of a bovine pericardial patch.
AB - Left ventricular aneurysm, which can impair systolic function, has a reported
incidence of 10% to 35% in patients after myocardial infarction. In a 58-year-old
woman who had a history of myocardial infarction, we excised a large left
ventricular aneurysm and restored left ventricular geometry with use of a bovine
pericardial patch. The aneurysm's characteristics and the patient's preoperative
left ventricular ejection fraction of 0.25 had indicated surgical intervention.
The patient had an uneventful postoperative course, and her left ventricular
ejection fraction was 0.50 to 0.55 on the 4th postoperative day. This case
illustrates the value of surgical treatment for patients who have a debilitating
left ventricular aneurysm.
PMID- 25120395
TI - Coarctation of persistent 5th aortic arch: first report of catheter-based
intervention.
AB - Persistent 5th aortic arch, originally called double-lumen aortic arch, is a
rarely reported cardiac developmental anomaly that results in systemic-to
systemic or systemic-to-pulmonary shunting. When this malformation occurs, other
intracardiac defects are almost always present. We report the case of a 7-month
old girl who presented with a heart murmur; she was found to have an interrupted
4th aortic arch and coarctation of a persistent 5th aortic arch, with no other
defects. To our knowledge, this is the 3rd report of a pediatric patient with
this condition in isolation, and the first report of its diagnosis and treatment
by means of cardiac catheterization and balloon angioplasty.
PMID- 25120396
TI - Left main coronary artery obstruction by dislodged native-valve calculus after
transcatheter aortic valve replacement.
AB - Transcatheter aortic valve replacement can be an effective, reliable treatment
for severe aortic stenosis in surgically high-risk or ineligible patients.
However, various sequelae like coronary artery obstruction can occur, not only in
the long term, but also immediately after the procedure. We present the case of a
78-year-old woman whose left main coronary artery became obstructed with calculus
2 hours after the transfemoral implantation of an Edwards Sapien XT aortic valve.
Despite percutaneous coronary intervention in that artery, the patient died. This
case reminds us that early recognition of acute coronary obstruction and prompt
intervention are crucial in patients with aortic stenosis who have undergone
transcatheter aortic valve replacement.
PMID- 25120397
TI - Cor triatriatum dexter and atrial septal defect in a 43-year-old woman.
AB - Cor triatriatum dexter is a rare congenital heart anomaly in which a membrane
divides the right atrium into 2 chambers. We report the case of a 43-year-old
woman who had cor triatriatum dexter and a large atrial septal defect. During
attempted percutaneous closure, the balloon disrupted the membrane and revealed
that the defect had no inferior rim, precluding secure placement of an Amplatzer
Septal Occluder. Surgical treatment subsequently proved to be successful. In
patients with an incomplete membrane and a septal defect with well-defined rims,
percutaneous treatment can be the first choice. In patients who have cor
triatriatum dexter and unfavorable anatomic features or concomitant complex heart
anomalies, open-heart surgery remains the gold standard for treatment.
PMID- 25120398
TI - Concomitant reconstruction of arch vessels during repair of aortic dissection.
AB - Surgery for acute aortic dissection is challenging, especially in cases of
cerebral malperfusion. Should we perform only the aortic repair, or should we
also reconstruct the arch vessels when they are severely affected by the disease
process? Here we present a case of acute aortic dissection with multiple tears
that involved the brachiocephalic artery and caused cerebral and right upper
extremity malperfusion. The patient successfully underwent complete replacement
of the brachiocephalic artery and the aortic arch during deep hypothermic
circulatory arrest, with antegrade cerebral protection. We have found this
technique to be safe and reproducible for use in this group of patients.
PMID- 25120399
TI - Right ventricular outflow tract obstruction caused by double-chambered right
ventricle presenting in adulthood.
AB - Congenital heart diseases that cause obstruction of the right ventricular outflow
tract are often difficult to diagnose. We report the case of a 49-year-old man
who presented with long-standing shortness of breath on exertion. Imaging
revealed right ventricular outflow tract obstruction caused by a double-chambered
right ventricle, and he was referred for surgical correction. This case
emphasizes both the detailed perioperative evaluation that is needed when
diagnosing adults who present with manifestations of congenital heart disease and
a method of successful surgical correction that resulted in symptom resolution.
PMID- 25120400
TI - Penetrating nail-gun injury of the heart managed by adenosine-induced asystole in
the absence of a heart-lung machine.
AB - During his work, an 18-year-old carpenter-in-training overbalanced and shot
himself in the left median thorax with a nail gun. The patient was delivered to
our thoracic surgery unit with a tentative diagnosis of penetrating lung trauma.
An emergent computed tomogram showed a heart-penetrating nail injury. The patient
was taken to the operating room, where he underwent emergency surgery that
included sternotomy, pericardiotomy, extraction of the nail, and trauma treatment
of the heart injury. The surgery was performed in a unit without a heart-lung
machine. For that reason, asystole was chemically induced by the intravenous
administration of adenosine. The surgery was successful, and the patient was
discharged from the hospital on the 10th postoperative day. In cases of
penetrating injuries of the heart, especially those with a foreign body retained
in situ, we believe that the intravenous administration of adenosine is an
elegant solution for the rapid provocation of asystole. In contrast to other
methods, adenosine-induced asystole enables relatively safe myocardial
manipulation in the absence of a cardiac surgical unit and a heart-lung machine.
PMID- 25120402
TI - Septic coronary artery embolism treated with aspiration thrombectomy: case report
and review of literature.
AB - Coronary embolization is a potentially fatal sequela of endocarditis. We report a
case of Candida endocarditis with septic embolism to the left anterior descending
coronary artery. This embolism was successfully treated with aspiration
thrombectomy followed by balloon angioplasty. The treatment of acute coronary
syndrome in the presence of septic embolism is controversial. Aspiration
thrombectomy has been performed in this situation before, and it appears to be
safer and more feasible than is thrombolysis or percutaneous transluminal
angioplasty.
PMID- 25120401
TI - Intimal sarcoma in the aortic arch partially obstructing the aorta with
metastasis to the brain.
AB - Primary tumors of the aorta are rare entities. We report the unusual
manifestation of an aortic intimal sarcoma that presented as a brain metastasis
in a 56-year-old, otherwise healthy woman. After the brain mass had been
resected, multiple imaging methods revealed pseudocoarctation and the primary
tumor in the aortic arch. To our knowledge, this is the first report of the
diagnosis of an aortic intimal sarcoma with use of real-time, 3-dimensional
transesophageal echocardiography.
PMID- 25120403
TI - Intraoperative surgical sealant application during cardiac defect repair.
AB - Bleeding can occur as a sequela to cardiac surgery. Surgical products-such as
conventional sutures and clips, and somewhat less conventional sealants-have been
developed to prevent this event. Among these, CoSeal is a sealant used at our
institution; here we report the cases of 2 patients in whom CoSeal was used
successfully as either a supplement or an alternative to suture repair. This
sealant was found to be useful in attaining hemostasis both in high-pressure
ventricular repair and in the rupture of a friable coronary sinus adjacent to
vital structures (in this instance, a left circumflex coronary artery).
PMID- 25120404
TI - Left-atrial-appendage occluder migrates in an asymptomatic patient.
AB - Percutaneous closure of the left atrial appendage (LAA) is a new approach to the
prevention of cardioembolic events in patients with atrial fibrillation. We
implanted an LAA occlusion device (AmplatzerTM Cardiac Plug) in a 70-year-old
woman via a transseptal approach. Upon her discharge from the hospital, a
transthoracic echocardiogram showed stable anchoring of the device; 6 months
after implantation, a routine transthoracic echocardiogram revealed migration of
the occluder into the left ventricular outflow tract, in the absence of symptoms.
We surgically removed the device from the mitral subvalvular apparatus and closed
the LAA with sutures. This case shows that percutaneous LAA occlusion can result
in serious adverse events, including device migration in the absence of signs or
symptoms; therefore, careful follow-up monitoring is mandatory.
PMID- 25120405
TI - Finding a lost coronary stent months later with use of multimethod imaging.
PMID- 25120406
TI - Commissural prolapse of the mitral valve identified on 3-dimensional
transesophageal echocardiography.
PMID- 25120407
TI - Association of left ventricular noncompaction with polycystic kidney disease as
shown by cardiac magnetic resonance imaging.
PMID- 25120408
TI - Acute paraplegia during weightlifting: an unusual vascular catastrophe.
PMID- 25120409
TI - More on weightlifting injuries.
PMID- 25120410
TI - Low-amplitude electrocardiogram in a patient with atrial fibrillation, direct
current electrical cardioversion, and takotsubo cardiomyopathy.
PMID- 25120412
TI - Yet another Bradford's law: new evidence on integrated care from Japan.
PMID- 25120411
TI - Health related quality of life and parental perceptions of child vulnerability
among parents of a child with juvenile idiopathic arthritis: results from a web
based survey.
AB - BACKGROUND: A chronic illness, such as Juvenile Idiopathic Arthritis (JIA), has
an impact on the whole family, especially on parents caring for the ill child.
Therefore the aim of this study is to evaluate parental Health Related Quality of
Life (HRQOL) and parental perceptions of child vulnerability (PPCV) and
associated variables in parents of a child with JIA. METHODS: Parents of all JIA
patients (0-18 years) in Amsterdam, the Netherlands, were eligible. HRQOL was
measured using the TNO-AZL Questionnaire (TAAQOL) and PPCV using the Child
Vulnerability Scale (CVS). The HRQOL of parents of a child with JIA was compared
to a norm population, and differences between parents of a child with JIA and
active arthritis versus parents of a child with JIA without active arthritis were
analyzed (ANOVA). For PPCV, parents of a child with JIA were compared to a norm
population, including healthy and chronically ill children (Chi(2), Mann-Whitney
U test). Variables associated with PPCV were identified by logistic regression
analyses. RESULTS: 155 parents (87.5% mothers) completed online questionnaires.
JIA parents showed worse HRQOL than parents of healthy children on one out of
twelve domains: fine motor HRQOL (p < .001). Parents of children with active
arthritis showed worse HRQOL regarding daily activities (p < .05), cognitive
functioning (p < .01) and depressive emotions (p < .05) compared to parents of
children without active arthritis. Parents of children with JIA perceived their
child as more vulnerable than parents of a healthy child (p < .001) and parents
of a chronically ill child (p < .001). Parents of children with active arthritis
reported higher levels of PPCV (p < .05) than parents of children without active
arthritis. A higher degree of functional disability (p < .01) and shorter disease
duration (p < .05) were associated with higher levels of PPCV. CONCLUSION: The
HRQOL of JIA parents was comparable to the HRQOL of parents of a healthy child.
JIA parents of a child with active arthritis showed worse HRQOL than parents of a
child without active arthritis. Parents perceived their child with JIA as
vulnerable.
PMID- 25120413
TI - Methodological development of the interactive INTERLINKS Framework for Long-term
Care.
AB - There is increasing international research into health and social care services
for older people in need of long-term care (LTC), but problems remain with
respect to acquiring robust comparative information to enable judgements to be
made regarding the most beneficial and cost-effective approaches. The project
'INTERLINKS' ('Health systems and LTC for older people in Europe') funded by the
EU 7th Framework programme was developed to address the challenges associated
with the accumulation and comparison of evidence in LTC across Europe. It
developed a concept and method to describe and analyse LTC and its links with the
health and social care system through the accumulation of policy and practice
examples on an interactive web-based framework for LTC. This paper provides a
critical overview of the theoretical and methodological approaches used to
develop and implement the INTERLINKS Framework for LTC, with the aim of providing
some guidance to researchers in this area. INTERLINKS has made a significant
contribution to knowledge but robust evidence and comparability across European
countries remain problematic due to the current and growing complexity and
diversity of integrated LTC implementation.
PMID- 25120414
TI - Esophageal Perforation due to Transesophageal Echocardiogram: New Endoscopic Clip
Treatment.
AB - Esophageal perforation due to transesophageal echocardiogram (TEE) during cardiac
surgery is rare. A 72-year-old female underwent TEE during an operation for
aortic valve replacement. Further, the patient presented hematemesis. Gastroscopy
revealed an esophageal bleeding ulcer. Endoscopic therapy was successful.
Although a CT scan excluded perforation, the patient became febrile, and a second
gastroscopy revealed a big perforation at the site of ulcer. The patient's
clinical condition required endoscopic intervention with a new OTSC((r)) clip
(Ovesco Endoscopy, Tubingen, Germany). The perforation was successfully sealed.
The patient remained on intravenous antibiotics, proton pump inhibitors and
parenteral nutrition for few days, followed by enteral feeding. She was
discharged fully recovered 3 months later. We clearly demonstrate an effective,
less invasive treatment of an esophageal perforation with a new endoscopic clip.
PMID- 25120415
TI - Severe Colitis Associated with both Epstein-Barr Virus and Cytomegalovirus
Reactivation in a Patient with Severe Aplastic Anemia.
AB - Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are members of the herpesvirus
family and common causes of viral infection in humans. CMV infection of the
gastrointestinal tract occurs mainly in immunocompromised individuals, on the
other hand EBV infection and reactivation involving the gastrointestinal tract is
very rare. A 56-year-old man was diagnosed with severe aplastic anemia and
treated with antithymocyte globulin (ATG) and cyclosporine (CSP). After 2 years
of ATG/CSP therapy, he suddenly started passing bloody diarrhea and developed a
high fever despite CSP treatment. Endoscopic features included severe edema and
multiple superficial ulcers; the patient was initially diagnosed with severe
colitis resembling inflammatory bowel disease (IBD). However, his symptoms did
not resolve with steroid treatment. Immunohistochemical analysis of samples
obtained from a second colonoscopy showed cells positive for CMV, and in situ
hybridization revealed EBV-encoded small RNA-1-positive cells. Additionally, the
patient's serum was positive for C7-HRP, and both blood and colon tissues were
positive for EBV DNA, which was detected using PCR analysis. We finally diagnosed
the patient with colitis associated with reactivation of both CMV and EBV. The
patient remains diarrhea-free after 1.5 years with scheduled globulin treatment
and after cessation of immunosuppressive drug therapy. To our knowledge, this is
the first reported case of an immunodeficient patient with severe hemorrhagic
colitis that was associated with reactivation of both EBV and CMV, and whose
endoscopic findings mimicked IBD.
PMID- 25120416
TI - Characterization of primary afferent spinal innervation of mouse uterus.
AB - The primary afferent innervation of the uterus is incompletely understood. The
aim of this study was to identify the location and characteristics of primary
afferent neurons that innervate the uterine horn of mice and correlate the
different morphological types of putative primary afferent nerve endings,
immunoreactive to the sensory marker, calcitonin gene related peptide (CGRP).
Using retrograde tracing, injection of 5-10 MUL of 1,1'-didodecyl-3,3,3,3'
tetramethylindocarbocyanine perchlorate (DiI) into discrete single sites in each
uterine horn revealed a biomodal distribution of sensory neurons in dorsal root
ganglia (DRG) with peak labeling occurring between T13-L3 and a second smaller
peak between L6-S1. The mean cross sectional area of labeled cells was 463 MUm(2)
+/- s.e.m. A significantly greater proportion of labeled neurons consisted of
small cell bodies (<300 MUm(2)) in the sacral spinal cord (S2) compared with peak
labeling at the lumbar (L2) region. In both sections and whole mount
preparations, immunohistochemical staining for CGRP revealed substantial
innervation of the uterus by CGRP-positive nerve fibers located primarily at the
border between the circular and longitudinal muscle layers (N = 4). The nerve
endings were classified into three distinct types: "single," "branching," or
"complex," that often aligned preferentially in either the circular or
longitudinal axis of the smooth muscles. Complex endings were often associated
with mesenteric vessels. We have identified that the cell bodies of primary
afferent neurons innervating the mouse uterus lie primarily in DRG at L2 and S1
spinal levels. Also, the greatest density of CGRP immunoreactivity lies within
the myometrium, with at least three different morphological types of nerve
endings identified. These findings will facilitate further investigations into
the mechanisms underlying sensory transduction in mouse uterus.
PMID- 25120417
TI - Bidirectional control of a one-dimensional robotic actuator by operant
conditioning of a single unit in rat motor cortex.
AB - The design of efficient neuroprosthetic devices has become a major challenge for
the long-term goal of restoring autonomy to motor-impaired patients. One approach
for brain control of actuators consists in decoding the activity pattern obtained
by simultaneously recording large neuronal ensembles in order to predict in real
time the subject's intention, and move the prosthesis accordingly. An alternative
way is to assign the output of one or a few neurons by operant conditioning to
control the prosthesis with rules defined by the experimenter, and rely on the
functional adaptation of these neurons during learning to reach the desired
behavioral outcome. Here, several motor cortex neurons were recorded
simultaneously in head-fixed awake rats and were conditioned, one at a time, to
modulate their firing rate up and down in order to control the speed and
direction of a one-dimensional actuator carrying a water bottle. The goal was to
maintain the bottle in front of the rat's mouth, allowing it to drink. After
learning, all conditioned neurons modulated their firing rate, effectively
controlling the bottle position so that the drinking time was increased relative
to chance. The mean firing rate averaged over all bottle trajectories depended
non-linearly on position, so that the mouth position operated as an attractor.
Some modifications of mean firing rate were observed in the surrounding neurons,
but to a lesser extent. Notably, the conditioned neuron reacted faster and led to
a better control than surrounding neurons, as calculated by using the activity of
those neurons to generate simulated bottle trajectories. Our study demonstrates
the feasibility, even in the rodent, of using a motor cortex neuron to control a
prosthesis in real-time bidirectionally. The learning process includes
modifications of the activity of neighboring cortical neurons, while the
conditioned neuron selectively leads the activity patterns associated with the
prosthesis control.
PMID- 25120418
TI - Longitudinal changes in task-evoked brain responses in Parkinson's disease
patients with and without mild cognitive impairment.
AB - Cognitive deficits are common in Parkinson's disease. Previous cross-sectional
research has demonstrated a link between cognitive impairments and fronto
striatal dopaminergic dysmodulation. However, longitudinal studies that link
disease progression with altered task-evoked brain activity are lacking.
Therefore, our objective was to longitudinally evaluate working-memory related
brain activity changes in Parkinson's disease patients with and without mild
cognitive impairment (MCI). Patients were recruited within a longitudinal cohort
study of incident patients with idiopathic parkinsonism. We longitudinally (at
baseline examination and at 12-months follow-up) compared 28 patients with
Parkinson's disease without MCI with 11 patients with Parkinson's disease and
MCI. Functional MRI blood oxygen level dependent signal was measured during a
verbal two-back working-memory task. Patients with MCI under-recruited bilateral
medial prefrontal cortex at both time-points (main effect of group: p < 0.001,
uncorrected). Critically, a significant group-by-time interaction effect (p <
0.001, uncorrected) was found in the right fusiform gyrus, indicating that
working-memory related activity decreased for patients with Parkinson's disease
and MCI between baseline and follow-up, while patients without MCI were stable
across time-points. The functional connectivity between right fusiform gyrus and
bilateral caudate nucleus was stronger for patients without MCI relative to
patients with MCI. Our findings support the view that deficits in working-memory
updating are related to persistent fronto-striatal under-recruitments in patients
with early phase Parkinson's disease and MCI. The longitudinal evolution of MCI
in Parkinson's disease translates into additional task-evoked posterior cortical
changes.
PMID- 25120419
TI - Origin and function of short-latency inputs to the neural substrates underlying
the acoustic startle reflex.
AB - The acoustic startle reflex (ASR) is a survival mechanism of alarm, which rapidly
alerts the organism to a sudden loud auditory stimulus. In rats, the primary ASR
circuit encompasses three serially connected structures: cochlear root neurons
(CRNs), neurons in the caudal pontine reticular nucleus (PnC), and motoneurons in
the medulla and spinal cord. It is well-established that both CRNs and PnC
neurons receive short-latency auditory inputs to mediate the ASR. Here, we
investigated the anatomical origin and functional role of these inputs using a
multidisciplinary approach that combines morphological, electrophysiological and
behavioral techniques. Anterograde tracer injections into the cochlea suggest
that CRNs somata and dendrites receive inputs depending, respectively, on their
basal or apical cochlear origin. Confocal colocalization experiments demonstrated
that these cochlear inputs are immunopositive for the vesicular glutamate
transporter 1 (VGLUT1). Using extracellular recordings in vivo followed by
subsequent tracer injections, we investigated the response of PnC neurons after
contra-, ipsi-, and bilateral acoustic stimulation and identified the source of
their auditory afferents. Our results showed that the binaural firing rate of PnC
neurons was higher than the monaural, exhibiting higher spike discharges with
contralateral than ipsilateral acoustic stimulations. Our histological analysis
confirmed the CRNs as the principal source of short-latency acoustic inputs, and
indicated that other areas of the cochlear nucleus complex are not likely to
innervate PnC. Behaviorally, we observed a strong reduction of ASR amplitude in
monaural earplugged rats that corresponds with the binaural summation process
shown in our electrophysiological findings. Our study contributes to understand
better the role of neuronal mechanisms in auditory alerting behaviors and
provides strong evidence that the CRNs-PnC pathway mediates fast
neurotransmission and binaural summation of the ASR.
PMID- 25120420
TI - Urinary oxytocin positively correlates with performance in facial visual search
in unmarried males, without specific reaction to infant face.
AB - The neuropeptide oxytocin plays a central role in prosocial and parental behavior
in non-human mammals as well as humans. It has been suggested that oxytocin may
affect visual processing of infant faces and emotional reaction to infants.
Healthy male volunteers (N = 13) were tested for their ability to detect infant
or adult faces among adult or infant faces (facial visual search task). Urine
samples were collected from all participants before the study to measure the
concentration of oxytocin. Urinary oxytocin positively correlated with
performance in the facial visual search task. However, task performance and its
correlation with oxytocin concentration did not differ between infant faces and
adult faces. Our data suggests that endogenous oxytocin is related to facial
visual cognition, but does not promote infant-specific responses in unmarried men
who are not fathers.
PMID- 25120421
TI - Removing ballistocardiogram (BCG) artifact from full-scalp EEG acquired inside
the MR scanner with Orthogonal Matching Pursuit (OMP).
AB - Ballistocardiogram (BCG) artifact remains a major challenge that renders
electroencephalographic (EEG) signals hard to interpret in simultaneous EEG and
functional MRI (fMRI) data acquisition. Here, we propose an integrated learning
and inference approach that takes advantage of a commercial high-density EEG cap,
to estimate the BCG contribution in noisy EEG recordings from inside the MR
scanner. To estimate reliably the full-scalp BCG artifacts, a near-optimal subset
(20 out of 256) of channels first was identified using a modified recording
setup. In subsequent recordings inside the MR scanner, BCG-only signal from this
subset of channels was used to generate continuous estimates of the full-scalp
BCG artifacts via inference, from which the intended EEG signal was recovered.
The reconstruction of the EEG was performed with both a direct subtraction and an
optimization scheme. We evaluated the performance on both synthetic and real
contaminated recordings, and compared it to the benchmark Optimal Basis Set (OBS)
method. In the challenging non-event-related-potential (non-ERP) EEG studies, our
reconstruction can yield more than fourteen-fold improvement in reducing the
normalized RMS error of EEG signals, compared to OBS.
PMID- 25120423
TI - Processing of spatial sounds in human auditory cortex during visual,
discrimination and 2-back tasks.
AB - Previous imaging studies on the brain mechanisms of spatial hearing have mainly
focused on sounds varying in the horizontal plane. In this study, we compared
activations in human auditory cortex (AC) and adjacent inferior parietal lobule
(IPL) to sounds varying in horizontal location, distance, or space (i.e.,
different rooms). In order to investigate both stimulus-dependent and task
dependent activations, these sounds were presented during visual discrimination,
auditory discrimination, and auditory 2-back memory tasks. Consistent with
previous studies, activations in AC were modulated by the auditory tasks. During
both auditory and visual tasks, activations in AC were stronger to sounds varying
in horizontal location than along other feature dimensions. However, in IPL, this
enhancement was detected only during auditory tasks. Based on these results, we
argue that IPL is not primarily involved in stimulus-level spatial analysis but
that it may represent such information for more general processing when relevant
to an active auditory task.
PMID- 25120422
TI - A review on auditory space adaptations to altered head-related cues.
AB - In this article we present a review of current literature on adaptations to
altered head-related auditory localization cues. Localization cues can be altered
through ear blocks, ear molds, electronic hearing devices, and altered head
related transfer functions (HRTFs). Three main methods have been used to induce
auditory space adaptation: sound exposure, training with feedback, and explicit
training. Adaptations induced by training, rather than exposure, are consistently
faster. Studies on localization with altered head-related cues have reported poor
initial localization, but improved accuracy and discriminability with training.
Also, studies that displaced the auditory space by altering cue values reported
adaptations in perceived source position to compensate for such displacements.
Auditory space adaptations can last for a few months even without further contact
with the learned cues. In most studies, localization with the subject's own
unaltered cues remained intact despite the adaptation to a second set of cues.
Generalization is observed from trained to untrained sound source positions, but
there is mixed evidence regarding cross-frequency generalization. Multiple brain
areas might be involved in auditory space adaptation processes, but the auditory
cortex (AC) may play a critical role. Auditory space plasticity may involve
context-dependent cue reweighting.
PMID- 25120424
TI - Automatic real-time monitoring and assessment of tremor parameters in the upper
limb from orientation data.
AB - Upper limb tremor is the most prevalent movement disorder and, unfortunately, it
is not effectively managed in a large proportion of the patients. Neuroprostheses
that stimulate the sensorimotor pathways are one of the most promising
alternatives although they are still under development. To enrich the
interpretation of data recorded during long-term tremor monitoring and to
increase the intelligence of tremor suppression neuroprostheses we need to be
aware of the context. Context awareness is a major challenge for neuroprostheses
and would allow these devices to react more quickly and appropriately to the
changing demands of the user and/or task. Traditionally kinematic features are
used to extract context information, with most recently the use of joint angles
as highly potential features. In this paper we present two algorithms that enable
the robust extraction of joint angle and related features to enable long-term
continuous monitoring of tremor with context awareness. First, we describe a
novel relative sensor placement identification technique based on orientation
data. We focus on relative rather than absolute sensor location, because in many
medical applications magnetic and inertial measurement units (MIMU) are used in a
chain stretching over adjacent segments, or are always placed on a fixed set of
locations. Subsequently we demonstrate how tremor parameters can be extracted
from orientation data using an adaptive estimation algorithm. Relative sensor
location was detected with an accuracy of 94.12% for the 4 MIMU configuration,
and 100% for the 3 MIMU configurations. Kinematic tracking error values with an
average deviation of 8% demonstrate our ability to estimate tremor from
orientation data. The methods presented in this study constitute an important
step toward more user-friendly and context-aware neuroprostheses for tremor
suppression and monitoring.
PMID- 25120425
TI - A new paradigm to induce mental stress: the Sing-a-Song Stress Test (SSST).
AB - We here introduce a new experimental paradigm to induce mental stress in a quick
and easy way while adhering to ethical standards and controlling for potential
confounds resulting from sensory input and body movements. In our Sing-a-Song
Stress Test, participants are presented with neutral messages on a screen,
interleaved with 1-min time intervals. The final message is that the participant
should sing a song aloud after the interval has elapsed. Participants sit still
during the whole procedure. We found that heart rate and skin conductance during
the 1-min intervals following the sing-a-song stress message are substantially
higher than during intervals following neutral messages. The order of magnitude
of the rise is comparable to that achieved by the Trier Social Stress Test. Skin
conductance increase correlates positively with experienced stress level as
reported by participants. We also simulated stress detection in real time. When
using both skin conductance and heart rate, stress is detected for 18 out of 20
participants, approximately 10 s after onset of the sing-a-song message. In
conclusion, the Sing-a-Song Stress Test provides a quick, easy, controlled and
potent way to induce mental stress and could be helpful in studies ranging from
examining physiological effects of mental stress to evaluating interventions to
reduce stress.
PMID- 25120427
TI - Investigating the effect of modifying the EEG cap lead configuration on the
gradient artifact in simultaneous EEG-fMRI.
AB - EEG data recorded during simultaneous fMRI are contaminated by large voltages
generated by time-varying magnetic field gradients. Correction of the resulting
gradient artifact (GA) generally involves low-pass filtering to attenuate the
high-frequency voltage fluctuations of the GA, followed by subtraction of a GA
template produced by averaging over repeats of the artifact waveforms. This
average artifact subtraction (AAS) process relies on the EEG amplifier having a
large enough dynamic range to characterize the artifact voltages and on
invariance of the artifact waveform over repeated image acquisitions. Saturation
of the amplifiers and changes in subject position can leave unwanted residual GA
after AAS. Previous modeling work suggested that modifying the lead layout and
the exit position of the cable bundle on the EEG cap could reduce the GA
amplitude. Here, we used simulations and experiments to evaluate the effect of
modifying the lead paths on the magnitude of the GA and on the residual artifact
after AAS. The modeling work showed that for wire paths following great circles,
the smallest overall GA occurs when the leads converge at electrode Cz. The
performance of this new cap design was compared with a standard cap in
experiments on a spherical agar phantom and human subjects. Using gradient pulses
applied separately along the three Cartesian axes, we found that the GA due to
the foot-head gradient was most significantly reduced relative to a standard cap
for the phantom, whereas the anterior-posterior GA was most attenuated for human
subjects. In addition, there was an overall 37% reduction in the RMS GA amplitude
produced by a standard EPI sequence when comparing the two caps on the phantom.
In contrast, the subjects showed an 11% increase in the average RMS of the GA.
This work shows that the optimal design reduces the GA on a spherical phantom
however; these gains are not translated to human subjects, probably due to the
differences in geometry.
PMID- 25120428
TI - Regulation and targeting of enzymes mediating Parkinson's disease pathogenesis:
focus on Parkinson's disease kinases, GTPases, and ATPases.
PMID- 25120426
TI - An anatomical and functional topography of human auditory cortical areas.
AB - While advances in magnetic resonance imaging (MRI) throughout the last decades
have enabled the detailed anatomical and functional inspection of the human brain
non-invasively, to date there is no consensus regarding the precise subdivision
and topography of the areas forming the human auditory cortex. Here, we propose a
topography of the human auditory areas based on insights on the anatomical and
functional properties of human auditory areas as revealed by studies of cyto- and
myelo-architecture and fMRI investigations at ultra-high magnetic field (7
Tesla). Importantly, we illustrate that-whereas a group-based approach to analyze
functional (tonotopic) maps is appropriate to highlight the main tonotopic axis
the examination of tonotopic maps at single subject level is required to detail
the topography of primary and non-primary areas that may be more variable across
subjects. Furthermore, we show that considering multiple maps indicative of
anatomical (i.e., myelination) as well as of functional properties (e.g.,
broadness of frequency tuning) is helpful in identifying auditory cortical areas
in individual human brains. We propose and discuss a topography of areas that is
consistent with old and recent anatomical post-mortem characterizations of the
human auditory cortex and that may serve as a working model for neuroscience
studies of auditory functions.
PMID- 25120429
TI - Spike generation estimated from stationary spike trains in a variety of neurons
in vivo.
AB - To any model of brain function, the variability of neuronal spike firing is a
problem that needs to be taken into account. Whereas the synaptic integration can
be described in terms of the original Hodgkin-Huxley (H-H) formulations of
conductance-based electrical signaling, the transformation of the resulting
membrane potential into patterns of spike output is subjected to stochasticity
that may not be captured with standard single neuron H-H models. The dynamics of
the spike output is dependent on the normal background synaptic noise present in
vivo, but the neuronal spike firing variability in vivo is not well studied. In
the present study, we made long-term whole cell patch clamp recordings of
stationary spike firing states across a range of membrane potentials from a
variety of subcortical neurons in the non-anesthetized, decerebrated state in
vivo. Based on the data, we formulated a simple, phenomenological model of the
properties of the spike generation in each neuron that accurately captured the
stationary spike firing statistics across all membrane potentials. The model
consists of a parametric relationship between the mean and standard deviation of
the inter-spike intervals, where the parameter is linearly related to the
injected current over the membrane. This enabled it to generate accurate
approximations of spike firing also under inhomogeneous conditions with input
that varies over time. The parameters describing the spike firing statistics for
different neuron types overlapped extensively, suggesting that the spike
generation had similar properties across neurons.
PMID- 25120432
TI - Stem cells for neonatal stroke- the future is here.
PMID- 25120430
TI - How big is the myelinating orchestra? Cellular diversity within the
oligodendrocyte lineage: facts and hypotheses.
AB - Since monumental studies from scientists like His, Ramon y Cajal, Lorente de No
and many others have put down roots for modern neuroscience, the scientific
community has spent a considerable amount of time, and money, investigating any
possible aspect of the evolution, development and function of neurons. Today, the
complexity and diversity of myriads of neuronal populations, and their
progenitors, is still focus of extensive studies in hundreds of laboratories
around the world. However, our prevalent neuron-centric perspective has dampened
the efforts in understanding glial cells, even though their active participation
in the brain physiology and pathophysiology has been increasingly recognized over
the years. Among all glial cells of the central nervous system (CNS),
oligodendrocytes (OLs) are a particularly specialized type of cells that provide
fundamental support to neuronal activity by producing the myelin sheath. Despite
their functional relevance, the developmental mechanisms regulating the
generation of OLs are still poorly understood. In particular, it is still not
known whether these cells share the same degree of heterogeneity of their
neuronal companions and whether multiple subtypes exist within the lineage. Here,
we will review and discuss current knowledge about OL development and function in
the brain and spinal cord. We will try to address some specific questions: do
multiple OL subtypes exist in the CNS? What is the evidence for their existence
and those against them? What are the functional features that define an
oligodendrocyte? We will end our journey by reviewing recent advances in human
pluripotent stem cell differentiation towards OLs. This exciting field is still
at its earliest days, but it is quickly evolving with improved protocols to
generate functional OLs from different spatial origins. As stem cells constitute
now an unprecedented source of human OLs, we believe that they will become an
increasingly valuable tool for deciphering the complexity of human OL identity.
PMID- 25120431
TI - Striatal cholinergic interneurons in isolated generalized dystonia-rationale and
perspectives for stem cell-derived cellular models.
AB - Interneurons comprise a minority of the striatal neuronal population of roughly
5%. However, this heterogeneous population is of particular interest as it
fulfills an important relay function in modulating the output of the only type of
striatal projection neurons, i.e., the medium spiny neuron (MSN).One subtype of
this heterogenous group, the cholinergic interneuron, is of particular scientific
interest as there is a relevant body of evidence from animal models supporting
its special significance in the disease process. The development of protocols for
directed differentiation of human pluripotent stem cells (PSC) into striatal
interneurons provides a unique opportunity to derive in vitro those cell types
that are most severely affected in dystonia.In this review we first aim to give a
concise overview about the normal function of striatal interneurons and their
dysfunction in dystonia in order to identify the most relevant interneuronal
subtype for the pathogenesis of dystonia. Secondly we demonstrate how knowledge
about the embryonic development of striatal interneurons is of particular help
for the development of differentiation protocols from PSC and by this depict
potential ways of deriving in vitro disease models of dystonia. We furthermore
address the question as to whether cell replacement therapies might represent a
beneficial approach for the treatment of dystonia.
PMID- 25120433
TI - Emerging role of the KCNT1 Slack channel in intellectual disability.
AB - The sodium-activated potassium KNa channels Slack and Slick are encoded by KCNT1
and KCNT2, respectively. These channels are found in neurons throughout the
brain, and are responsible for a delayed outward current termed I KNa. These
currents integrate into shaping neuronal excitability, as well as adaptation in
response to maintained stimulation. Abnormal Slack channel activity may play a
role in Fragile X syndrome, the most common cause for intellectual disability and
inherited autism. Slack channels interact directly with the fragile X mental
retardation protein (FMRP) and I KNa is reduced in animal models of Fragile X
syndrome that lack FMRP. Human Slack mutations that alter channel activity can
also lead to intellectual disability, as has been found for several childhood
epileptic disorders. Ongoing research is elucidating the relationship between
mutant Slack channel activity, development of early onset epilepsies and
intellectual impairment. This review describes the emerging role of Slack
channels in intellectual disability, coupled with an overview of the
physiological role of neuronal I KNa currents.
PMID- 25120435
TI - Gain control mechanisms in spinal motoneurons.
AB - Motoneurons provide the only conduit for motor commands to reach muscles. For
many years, motoneurons were in fact considered to be little more than passive
"wires". Systematic studies in the past 25 years however have clearly
demonstrated that the intrinsic electrical properties of motoneurons are under
strong neuromodulatory control via multiple sources. The discovery of potent
neuromodulation from the brainstem and its ability to change the gain of
motoneurons shows that the "passive" view of the motor output stage is no longer
tenable. A mechanism for gain control at the motor output stage makes good
functional sense considering our capability of generating an enormous range of
forces, from very delicate (e.g., putting in a contact lens) to highly forceful
(emergency reactions). Just as sensory systems need gain control to deal with a
wide dynamic range of inputs, so to might motor output need gain control to deal
with the wide dynamic range of the normal movement repertoire. Two problems
emerge from the potential use of the brainstem monoaminergic projection to
motoneurons for gain control. First, the projection is highly diffuse
anatomically, so that independent control of the gains of different motor pools
is not feasible. In fact, the system is so diffuse that gain for all the motor
pools in a limb likely increases in concert. Second, if there is a system that
increases gain, probably a system to reduce gain is also needed. In this review,
we summarize recent studies that show local inhibitory circuits within the spinal
cord, especially reciprocal and recurrent inhibition, have the potential to solve
both of these problems as well as constitute another source of gain modulation.
PMID- 25120436
TI - Inhibitory projections from the ventral nucleus of the trapezoid body to the
medial nucleus of the trapezoid body in the mouse.
AB - Neurons in the medial nucleus of the trapezoid body (MNTB) receive prominent
excitatory input through the calyx of Held, a giant synapse that produces large
and fast excitatory currents. MNTB neurons also receive inhibitory glycinergic
inputs that are also large and fast, and match the calyceal excitation in terms
of synaptic strength. GABAergic inputs provide additional inhibition to MNTB
neurons. Inhibitory inputs to MNTB modify spiking of MNTB neurons both in-vitro
and in-vivo, underscoring their importance. Surprisingly, the origin of the
inhibitory inputs to MNTB has not been shown conclusively. We performed
retrograde tracing, anterograde tracing, immunohistochemical experiments, and
electrophysiological recordings to address this question. The results support the
ventral nucleus of the trapezoid body (VNTB) as at least one major source of
glycinergic input to MNTB. VNTB fibers enter the ipsilateral MNTB, travel along
MNTB principal neurons and produce several bouton-like presynaptic terminals.
Further, the contribution of GABA to the total inhibition declines during
development, resulting in only a very minor fraction of GABAergic inhibition in
adulthood, which is matched in time by a reduction in expression of a GABA
synthetic enzyme in VNTB principal neurons.
PMID- 25120434
TI - A molecular web: endoplasmic reticulum stress, inflammation, and oxidative
stress.
AB - Execution of fundamental cellular functions demands regulated protein folding
homeostasis. Endoplasmic reticulum (ER) is an active organelle existing to
implement this function by folding and modifying secretory and membrane proteins.
Loss of protein folding homeostasis is central to various diseases and budding
evidences suggest ER stress as being a major contributor in the development or
pathology of a diseased state besides other cellular stresses. The trigger for
diseases may be diverse but, inflammation and/or ER stress may be basic
mechanisms increasing the severity or complicating the condition of the disease.
Chronic ER stress and activation of the unfolded-protein response (UPR) through
endogenous or exogenous insults may result in impaired calcium and redox
homeostasis, oxidative stress via protein overload thereby also influencing vital
mitochondrial functions. Calcium released from the ER augments the production of
mitochondrial Reactive Oxygen Species (ROS). Toxic accumulation of ROS within ER
and mitochondria disturbs fundamental organelle functions. Sustained ER stress is
known to potentially elicit inflammatory responses via UPR pathways.
Additionally, ROS generated through inflammation or mitochondrial dysfunction
could accelerate ER malfunction. Dysfunctional UPR pathways have been associated
with a wide range of diseases including several neurodegenerative diseases,
stroke, metabolic disorders, cancer, inflammatory disease, diabetes mellitus,
cardiovascular disease, and others. In this review, we have discussed the UPR
signaling pathways, and networking between ER stress-induced inflammatory
pathways, oxidative stress, and mitochondrial signaling events, which further
induce or exacerbate ER stress.
PMID- 25120439
TI - Plasma membrane transporters GAT-1 and GAT-3 contribute to heterogeneity of
GABAergic synapses in neocortex.
AB - Cortical GABAergic synapses exhibit a high degree of molecular, anatomical and
functional heterogeneity of their neurons of origins, presynaptic mechanisms,
receptors, and scaffolding proteins. GABA transporters (GATs) have an important
role in regulating GABA levels; among them, GAT-1 and GAT-3 play a prominent role
in modulating tonic and phasic GABAAR-mediated inhibition. We asked whether GAT-1
and GAT-3 contribute to generating heterogeneity by studying their
ultrastructural localization at cortical symmetric synapses using pre- and post
embedding electron microcopy. GAT-1 and GAT-3 staining at symmetric synapses
showed that in some cases the transporters were localized exclusively over axon
terminals; in others they were in both axon terminals and perisynaptic astrocytic
processes; and in some others GAT-1 and GAT-3 were in perisynaptic astrocytic
processes only. Moreover, we showed that the organizational pattern of GAT-1, but
not of GAT-3, exhibits a certain degree of specificity related to the post
synaptic target of GABAergic synapses. These findings show that symmetric
synapses expressing GAT-1 or GAT-3 are heterogeneous, and indicate that plasma
membrane transporters can contribute to synaptic heterogeneity.
PMID- 25120437
TI - Sound-by-sound thalamic stimulation modulates midbrain auditory excitability and
relative binaural sensitivity in frogs.
AB - Descending circuitry can modulate auditory processing, biasing sensitivity to
particular stimulus parameters and locations. Using awake in vivo single unit
recordings, this study tested whether electrical stimulation of the thalamus
modulates auditory excitability and relative binaural sensitivity in neurons of
the amphibian midbrain. In addition, by using electrical stimuli that were either
longer than the acoustic stimuli (i.e., seconds) or presented on a sound-by-sound
basis (ms), experiments addressed whether the form of modulation depended on the
temporal structure of the electrical stimulus. Following long duration electrical
stimulation (3-10 s of 20 Hz square pulses), excitability (spikes/acoustic
stimulus) to free-field noise stimuli decreased by 32%, but returned over 600 s.
In contrast, sound-by-sound electrical stimulation using a single 2 ms duration
electrical pulse 25 ms before each noise stimulus caused faster and varied forms
of modulation: modulation lasted <2 s and, in different cells, excitability
either decreased, increased or shifted in latency. Within cells, the modulatory
effect of sound-by-sound electrical stimulation varied between different acoustic
stimuli, including for different male calls, suggesting modulation is specific to
certain stimulus attributes. For binaural units, modulation depended on the ear
of input, as sound-by-sound electrical stimulation preceding dichotic acoustic
stimulation caused asymmetric modulatory effects: sensitivity shifted for sounds
at only one ear, or by different relative amounts for both ears. This caused a
change in the relative difference in binaural sensitivity. Thus, sound-by-sound
electrical stimulation revealed fast and ear-specific (i.e., lateralized)
auditory modulation that is potentially suited to shifts in auditory attention
during sound segregation in the auditory scene.
PMID- 25120440
TI - Differential processing of natural scenes in posterior cortical atrophy and in
Alzheimer's disease, as measured with a saccade choice task.
AB - Atrophy of the medial temporal lobe structures that support scene perception and
the binding of an object to its context (i.e., the hippocampus and the
parahippocampal cortex) appears early in the course of Alzheimer's disease (AD).
However, few studies have investigated scene perception in people with AD. Here,
we assessed the ability to find a target object within a natural scene in people
with AD and in people with posterior cortical atrophy (PCA, a variant of AD).
Pairs of color photographs were displayed on the left and right of a fixation
cross for 1 s. In separate blocks of trials, participants were asked to
categorize the target (an animal) by either moving their eyes toward the
photograph containing the target (the saccadic choice task) or pressing a key
corresponding to the target's location (the manual choice task). Isolated objects
and objects within scenes were studied in both tasks. Participants with PCA were
more impaired in detection of a target within a scene than participants with AD.
The latter's performance pattern was more similar to that of age-matched controls
in terms of accuracy, saccade latencies and the benefit gained from contextual
information. Participants with PCA benefited less from contextual information in
both the saccade and the manual choice tasks-suggesting that people with
posterior brain lesions have impairments in figure/ground segregation and are
more sensitive to object crowding.
PMID- 25120438
TI - Activation of lateral hypothalamus-projecting parabrachial neurons by intraorally
delivered gustatory stimuli.
AB - The present study investigated a subpopulation of neurons in the mouse
parabrachial nucleus (PbN), a gustatory and visceral relay area in the brainstem,
that project to the lateral hypothalamus (LH). We made injections of the
retrograde tracer Fluorogold (FG) into LH, resulting in fluorescent labeling of
neurons located in different regions of the PbN. Mice were stimulated through an
intraoral cannula with one of seven different taste stimuli, and PbN sections
were processed for immunohistochemical detection of the immediate early gene c
Fos, which labels activated neurons. LH projection neurons were found in all PbN
subnuclei, but in greater concentration in lateral subnuclei, including the
dorsal lateral subnucleus (dl). Fos-like immunoreactivity (FLI) was observed in
the PbN in a stimulus-dependent pattern, with the greatest differentiation
between intraoral stimulation with sweet (0.5 M sucrose) and bitter (0.003 M
quinine) compounds. In particular, sweet and umami-tasting stimuli evoked robust
FLI in cells in the dl, whereas quinine evoked almost no FLI in cells in this
subnucleus. Double-labeled cells were also found in the greatest quantity in the
dl. Overall, these results support the hypothesis that the dl contains direct a
projection to the LH that is activated preferentially by appetitive compounds;
this projection may be mediated by taste and/or postingestive mechanisms.
PMID- 25120442
TI - Executive function and bilingualism in young and older adults.
AB - Research suggests that being bilingual results in advantages on executive control
processes and disadvantages on language tasks relative to monolinguals.
Furthermore, the executive function advantage is thought to be larger in older
than younger adults, suggesting that bilingualism may buffer against age-related
changes in executive function. However, there are potential confounds in some of
the previous research, as well as inconsistencies in the literature. The goal of
the current investigation was to examine the presence of a bilingual advantage in
executive control and a bilingual disadvantage on language tasks in the same
sample of young and older monolingual anglophones, monolingual francophones, and
French/English bilinguals. Participants completed a series of executive function
tasks, including a Stroop task, a Simon task, a sustained attention to response
task (SART), the Wisconsin Card Sort Test (WCST), and the digit span subtest of
the Wechsler Adult Intelligence Scale, and language tasks, including the Boston
Naming Test (BNT), and category and letter fluency. The results do not
demonstrate an unequivocal advantage for bilinguals on executive function tasks
and raise questions about the reliability, robustness and/or specificity of
previous findings. The results also did not demonstrate a disadvantage for
bilinguals on language tasks. Rather, they suggest that there may be an influence
of the language environment. It is concluded that additional research is required
to fully characterize any language group differences in both executive function
and language tasks.
PMID- 25120441
TI - Niche convergence suggests functionality of the nocturnal fovea.
AB - The fovea is a declivity of the retinal surface associated with maximum visual
acuity. Foveae are widespread across vertebrates, but among mammals they are
restricted to haplorhine primates (tarsiers, monkeys, apes, and humans), which
are primarily diurnal. Thus primates have long contributed to the view that
foveae are functional adaptations to diurnality. The foveae of tarsiers, which
are nocturnal, are widely interpreted as vestigial traits and therefore evidence
of a diurnal ancestry. This enduring premise is central to adaptive hypotheses on
the origins of anthropoid primates; however, the question of whether tarsier
foveae are functionless anachronisms or nocturnal adaptations remains open. To
explore this question, we compared the diets of tarsiers (Tarsius) and scops owls
(Otus), taxa united by numerous anatomical homoplasies, including foveate vision.
A functional interpretation of these homoplasies predicts dietary convergence. We
tested this prediction by analyzing stable isotope ratios that integrate dietary
information. In Borneo and the Philippines, the stable carbon isotope
compositions of Tarsius and Otus were indistinguishable, whereas the stable
nitrogen isotope composition of Otus was marginally higher than that of Tarsius.
Our results indicate that species in both genera consumed mainly ground-dwelling
prey. Taken together, our findings support a functional interpretation of the
many homoplasies shared by tarsiers and scops owls, including a retinal fovea. We
suggest that the fovea might function similarly in tarsiers and scops owls by
calibrating the auditory localization pathway. The integration of auditory
localization and visual fixation during prey detection and acquisition might be
critical at low light levels.
PMID- 25120443
TI - On the generalizability of resting-state fMRI machine learning classifiers.
AB - Machine learning classifiers have become increasingly popular tools to generate
single-subject inferences from fMRI data. With this transition from the
traditional group level difference investigations to single-subject inference,
the application of machine learning methods can be seen as a considerable step
forward. Existing studies, however, have given scarce or no information on the
generalizability to other subject samples, limiting the use of such published
classifiers in other research projects. We conducted a simulation study using
publicly available resting-state fMRI data from the 1000 Functional Connectomes
and COBRE projects to examine the generalizability of classifiers based on
regional homogeneity of resting-state time series. While classification
accuracies of up to 0.8 (using sex as the target variable) could be achieved on
test datasets drawn from the same study as the training dataset, the
generalizability of classifiers to different study samples proved to be limited
albeit above chance. This shows that on the one hand a certain amount of
generalizability can robustly be expected, but on the other hand this
generalizability should not be overestimated. Indeed, this study substantiates
the need to include data from several sites in a study investigating machine
learning classifiers with the aim of generalizability.
PMID- 25120444
TI - Toward a new conception of habit and self-control in adolescent maturation.
PMID- 25120446
TI - Assessment of size ordered recruitment.
PMID- 25120445
TI - Roles of frontal and temporal regions in reinterpreting semantically ambiguous
sentences.
AB - Semantic ambiguity resolution is an essential and frequent part of speech
comprehension because many words map onto multiple meanings (e.g., "bark,"
"bank"). Neuroimaging research highlights the importance of the left inferior
frontal gyrus (LIFG) and the left posterior temporal cortex in this process but
the roles they serve in ambiguity resolution are uncertain. One possibility is
that both regions are engaged in the processes of semantic reinterpretation that
follows incorrect interpretation of an ambiguous word. Here we used fMRI to
investigate this hypothesis. 20 native British English monolinguals were scanned
whilst listening to sentences that contained an ambiguous word. To induce
semantic reinterpretation, the disambiguating information was presented after the
ambiguous word and delayed until the end of the sentence (e.g., "the teacher
explained that the BARK was going to be very damp"). These sentences were
compared to well-matched unambiguous sentences. Supporting the reinterpretation
hypothesis, these ambiguous sentences produced more activation in both the LIFG
and the left posterior inferior temporal cortex. Importantly, all but one subject
showed ambiguity-related peaks within both regions, demonstrating that the group
level results were driven by high inter-subject consistency. Further support came
from the finding that activation in both regions was modulated by meaning
dominance. Specifically, sentences containing biased ambiguous words, which have
one more dominant meaning, produced greater activation than those with balanced
ambiguous words, which have two equally frequent meanings. Because the context
always supported the less frequent meaning, the biased words require
reinterpretation more often than balanced words. This is the first evidence of
dominance effects in the spoken modality and provides strong support that frontal
and temporal regions support the updating of semantic representations during
speech comprehension.
PMID- 25120448
TI - Habit and embodiment in Merleau-Ponty.
PMID- 25120447
TI - The role of parietal cortex in the formation of color and motion based concepts.
AB - Imaging evidence shows that separate subdivisions of parietal cortex, in and
around the intraparietal sulcus (IPS), are engaged when stimuli are grouped
according to color and to motion (Zeki and Stutters, 2013). Since grouping is an
essential step in the formation of concepts, we wanted to learn whether parietal
cortex is also engaged in the formation of concepts according to these two
attributes. Using functional magnetic resonance imaging (fMRI), and choosing the
recognition of concept-based color or motion stimuli as our paradigm, we found
that there was strong concept-related activity in and around the IPS, a region
whose homolog in the macaque monkey is known to receive direct but segregated
anatomical inputs from V4 and V5. Parietal activity related to color concepts was
juxtaposed but did not overlap with activity related to motion concepts, thus
emphasizing the continuation of the segregation of color and motion into the
conceptual system. Concurrent retinotopic mapping experiments showed that within
the parietal cortex, concept-related activity increases within later stage IPS
areas.
PMID- 25120449
TI - Agency over a phantom limb and electromyographic activity on the stump depend on
visuomotor synchrony: a case study.
AB - Most patients, post-amputation, report the experience of a phantom limb. Some
even sense voluntary movements when viewing a mirror image of the intact limb
superimposed onto the phantom limb. While delayed visual feedback of an action is
known to reduce a sense of agency, the effect of delayed visual feedback on
phantom motor sensation (i.e., sense of controlling a phantom limb) has not been
examined. Using a video-projection system, we examined the effect of delayed
visual feedback on phantom motor sensation in an upper-limb amputee (male; left
upper-limb amputation). He was instructed to view mirrored video images of his
intact hand clasping and unclasping during a phantom limb movement. He then rated
the intensity of the phantom motor sensation. Three types of hand movement images
were presented as follows: synchronous, asynchronous with a 250-ms delay, and
asynchronous with a 500-ms delay. Results showed that phantom motor sensation
decreased when the image was delayed by 250 and 500 ms. However, when we
instructed the patient to adjust the phase of phantom limb movement to that of
the image with a 500-ms delay, phantom motor sensation increased. There was also
a positive correlation between intensity of phantom motor sensation and
electromyographic (EMG) activity on deltoids at the patient's stump. These
results suggest that phantom motor sensation and EMG activity on the stump depend
on visuomotor synchrony and top-down effects.
PMID- 25120450
TI - Neurofeminism and feminist neurosciences: a critical review of contemporary brain
research.
AB - To date, feminist approaches to neurosciences have evaluated the debates
surrounding practices of knowledge production within and research results of
contemporary brain research. Consequently, neurofeminist scholars have critically
examined gendered impacts of neuroscientific research. Feminist neuroscientists
also develop research approaches for a more gender-appropriate neuroscientific
research on several levels. Based on neurofeminist critique feminist
neuroscientists aim to enrich neuroscientific work by offering methodological
suggestions for a more differentiated setup of categories and experimental
designs, for reflective result presentations and interpretations as well as for
the analysis of result validity. Reframing neuro-epistemologies by including
plasticity concepts works to uncover social influences on the gendered
development of the brain and of behavior. More recently, critical work on
contemporary neurocultures has highlighted the entanglements of neuroscientific
research within society and the implications of 'neurofacts' for gendered
cultural symbolisms, social practices, and power relations. Not least,
neurofeminism critically analyses the portrayal of neuro-knowledge in popular
media. This article presents on overview on neurofeminist debates and on current
approaches of feminist neurosciences. The authors conclude their review by
calling for a more gender-appropriate research approach that takes into account
both its situatedness and reflections on the neuroscientific agenda, but also
questions neurofeminist discourse in regards to uses and misuses of its concepts.
PMID- 25120451
TI - Situated affective and social neuroscience.
PMID- 25120452
TI - Marking the counterfactual: ERP evidence for pragmatic processing of German
subjunctives.
AB - Counterfactual conditionals are frequently used in language to express
potentially valid reasoning from factually false suppositions. Counterfactuals
provide two pieces of information: their literal meaning expresses a
suppositional dependency between an antecedent (If the dice had been rigged...)
and a consequent (... then the game would have been unfair). Their second,
backgrounded meaning refers to the opposite state of affairs and suggests that,
in fact, the dice were not rigged and the game was fair. Counterfactual
antecedents are particularly intriguing because they set up a counterfactual
world which is known to be false, but which is nevertheless kept to when
evaluating the conditional's consequent. In the last years several event-related
potential (ERP) studies have targeted the processing of counterfactual
consequents, yet counterfactual antecedents have remained unstudied. We present
an EEG/ERP investigation which employed German conditionals to compare
subjunctive mood (which marks counterfactuality) with indicative mood at the
critical point of mood disambiguation via auxiliary introduction in the
conditional's antecedent. Conditional sentences were presented visually one word
at a time. Participants completed an acceptability judgment and probe detection
task which was not related to the critical manipulation of linguistic mood. ERPs
at the point of mood disambiguation in the antecedent were compared between
indicative and subjunctive. Our main finding is a transient negative deflection
in frontal regions for subjunctive compared to indicative mood in a time-window
of 450-600 ms. We discuss this novel finding in respect to working memory
requirements for rule application and increased referential processing demands
for the representation of counterfactuals' dual meaning. Our result suggests that
the counterfactually implied dual meaning is processed without any delay at the
earliest point where counterfactuality is marked by subjunctive mood.
PMID- 25120453
TI - Magnetoencephalographic study on facial movements.
AB - In this review, we introduced our three studies that focused on facial movements.
In the first study, we examined the temporal characteristics of neural responses
elicited by viewing mouth movements, and assessed differences between the
responses to mouth opening and closing movements and an averting eyes condition.
Our results showed that the occipitotemporal area, the human MT/V5 homologue, was
active in the perception of both mouth and eye motions. Viewing mouth and eye
movements did not elicit significantly different activity in the occipitotemporal
area, which indicated that perception of the movement of facial parts may be
processed in the same manner, and this is different from motion in general. In
the second study, we investigated whether early activity in the occipitotemporal
region evoked by eye movements was influenced by the facial contour and/or
features such as the mouth. Our results revealed specific information processing
for eye movements in the occipitotemporal region, and this activity was
significantly influenced by whether movements appeared with the facial contour
and/or features, in other words, whether the eyes moved, even if the movement
itself was the same. In the third study, we examined the effects of inverting the
facial contour (hair and chin) and features (eyes, nose, and mouth) on processing
for static and dynamic face perception. Our results showed the following: (1) In
static face perception, activity in the right fusiform area was affected more by
the inversion of features while that in the left fusiform area was affected more
by a disruption in the spatial relationship between the contour and features; and
(2) In dynamic face perception, activity in the right occipitotemporal area was
affected by the inversion of the facial contour.
PMID- 25120454
TI - Uni- and crossmodal refractory period effects of event-related potentials provide
insights into the development of multisensory processing.
AB - To assess uni- and multisensory development in humans, uni- and crossmodal event
related potential (ERP) refractory period effects were investigated. Forty-one
children from 4 to 12 years of age and 15 young adults performed a bimodal
oddball task with frequent and rare visual and auditory stimuli presented with
two different interstimulus intervals (ISIs). Amplitudes of the visual and
auditory ERPs were modulated as a function of the age of the participants, the
modality of the preceding stimulus (same vs. different) and the preceding ISI
(1000 or 2000 ms). While unimodal refractory period effects were observed in all
age groups, crossmodal refractory period effects differed among age groups. Early
crossmodal interactions (<150 ms) existing in the youngest age group (4-6 years)
disappeared, while later crossmodal interactions (>150 ms) emerged with a
parietal topography in older children and adults. Our results are compatible with
the intersensory differentiation and the multisensory perceptual narrowing
approach of multisensory development. Moreover, our data suggest that uni- and
multisensory development run in parallel with unimodal development leading.
PMID- 25120455
TI - Unconvincing support for role of mirror neurons in "action understanding":
commentary on Michael et al. (2014).
PMID- 25120456
TI - It's too quick to blame myself-the effects of fast and slow rates of change on
credit assignment during object lifting.
AB - Although there have been substantial research efforts examining the effect of
various rates of change in reaching movements, there has been little to no
research devoted to this issue during object manipulation tasks. In force-field
and visuomotor adaptation studies, two parallel processes have been identified:
first, a fast process that adapts and de-adapts quickly is thought to enable the
actor to deal with potentially transient perturbations. Second, a slower, but
longer lasting process adapts if these initial perturbations persist over time.
In a largely separate body of research, the role of credit assignment has been
examined in terms of allotting the cause of errors to changes in the body vs.
changes in the outside world. Of course, these two processes are usually linked
within the real world, with short lasting perturbations most often being linked
to external causes and longer lasting perturbations being linked to internal
causes. Here, we demonstrate that the increases in load forces associated with a
gradual increase in object weight during a natural object lifting task are
transferred when lifting a novel object, whereas a sudden increase in object
weight is not. We speculate that gradual rates of change in the weight of the
object being lifted are attributed to the self, whereas fast rates of change are
more likely to be attributed to the external environment. This study extends our
knowledge of the multiple timescales involved in motor learning to a more natural
object manipulation scenario, while concurrently providing support for the
hypothesis that the multiple time scales involved in motor learning are tuned for
different learning contexts.
PMID- 25120457
TI - The feedback related negativity encodes both social rejection and explicit social
expectancy violation.
AB - Humans consistently make predictions about the valence of future events and use
feedback to validate initial predictions. While the valence of outcomes provides
utilitarian information, the accuracy of predictions is crucial for future
performance adjustment. The feedback related negativity (FRN), identified as a
marker of reward prediction error, possibly encodes social rejection and social
prediction error. To test this possibility, we used event related potential (ERP)
techniques combined with social tasks in which participants were required to make
explicit predictions (whether others will accept their "friend request" or not,
Experiment 1) or implicit predictions (whether they would like this person or
not, Experiment 2) respectively, and then received social feedback. We found that
the FRN is sensitive to social rejection and explicit social prediction error in
Experiment 1 but not implicit social prediction error in Experiment 2. We
conclude that the FRN encodes social rejection and explicit social expectancy
violation.
PMID- 25120458
TI - Intraindividual reaction time variability affects P300 amplitude rather than
latency.
AB - The neural correlates of intraindividual response variability were investigated
in a serial choice reaction time (CRT) task. Reaction times (RTs) from the faster
and slower portions of the RT distribution for the task were separately
aggregated and associated P300 event-related potentials computed. Independent
behavioral measures of executive function and IQ were also recorded. Across
frontal, fronto-central, central, centro-parietal and parietal scalp regions,
P300 amplitudes were significantly greater for faster relative to slower
behavioral responses. However, P300 peak amplitude latencies did not differ
according to the speed of the behavioral RT. Importantly, controlling for select
independent measures of executive function attenuated shared variance in P300
amplitude for faster and slower trials. The findings suggest that P300 amplitude
rather than latency is associated with the speed of behavioral RTs, and the
possibility that fluctuations in executive control underlie variability in
speeded responding.
PMID- 25120459
TI - Does co-morbid obsessive-compulsive disorder modify the abnormal language
processing in schizophrenia patients? An FMRI study.
AB - BACKGROUND: Impaired language processing is one of the most replicated findings
in functional brain studies of schizophrenia (SCH). This is demonstrated by
reduced activations in left prefrontal language areas (i.e., BA44/45, the
inferior frontal gyrus, IFG) presented as decreased language lateralization. This
finding was documented both in chronic as well as in first-episode SCH patients,
arguing for a neurobiological marker for SCH. In a previous study, we
demonstrated the specificity of this finding to SCH patients when compared to
obsessive-compulsive disorder (OCD) patients in whom language processing was
similar to healthy controls. Since a sizable proportion of SCH patients also meet
DSM-IV criteria for OCD, we further sought to elucidate whether OCD attenuates
abnormal prefrontal language lateralization in this unique group of schizo
obsessive patients compared to their non-OCD-SCH counterparts. METHODS: We used
functional magnetic resonance imaging (fMRI) to investigate regional activation
and language lateralization in the left and right IFG and inter-hemispheric
functional connectivity (FC) during a language task of auditory verb generation
in 14 SCH patients with OCD, compared to 17 SCH patients without OCD, 13 OCD
patients and 14 healthy controls. RESULTS: No between-group differences were
found in the behavioral measurements of word generation. However, while OCD
patients were indistinguishable from healthy volunteers, a similarly reduced
lateralization in the IFG and diminished inter-hemispheric FC was noted in the
two SCH groups with and without OCD. CONCLUSION: The co-occurrence of OCD in SCH
does not attenuate abnormal processing of language as reflected by regional IFG
activity and FC. These results further support the notion that these language
processing abnormalities are characteristic of SCH and that SCH-OCD combined
psychopathology is more akin to SCH than to OCD.
PMID- 25120460
TI - Masking reveals parallel form systems in the visual brain.
AB - It is generally supposed that there is a single, hierarchically organized pathway
dedicated to form processing, in which complex forms are elaborated from simpler
ones, beginning with the orientation-selective cells of V1. In this
psychophysical study, we undertook to test another hypothesis, namely that the
brain's visual form system consists of multiple parallel systems and that complex
forms are other than the sum of their parts. Inspired by imaging experiments
which show that forms of increasing perceptual complexity (lines, angles, and
rhombuses) constituted from the same elements (lines) activate the same visual
areas (V1, V2, and V3) with the same intensity and latency (Shigihara and Zeki,
2013, 2014), we used backward masking to test the supposition that these forms
are processed in parallel. We presented subjects with lines, angles, and
rhombuses as different target-mask pairs. Evidence in favor of our supposition
would be if masking is the most effective when target and mask are processed by
the same system and least effective when they are processed in different systems.
Our results showed that rhombuses were strongly masked by rhombuses but only
weakly masked by lines or angles, but angles and lines were well masked by each
other. The relative resistance of rhombuses to masking by low-level forms like
lines and angles suggests that complex forms like rhombuses may be processed in a
separate parallel system, whereas lines and angles are processed in the same one.
PMID- 25120461
TI - Structure of receptive fields in a computational model of area 3b of primary
sensory cortex.
AB - In a previous work, we introduced a computational model of area 3b which is built
upon the neural field theory and receives input from a simplified model of the
index distal finger pad populated by a random set of touch receptors (Merkell
cells). This model has been shown to be able to self-organize following the
random stimulation of the finger pad model and to cope, to some extent, with
cortical or skin lesions. The main hypothesis of the model is that learning of
skin representations occurs at the thalamo-cortical level while cortico-cortical
connections serve a stereotyped competition mechanism that shapes the receptive
fields. To further assess this hypothesis and the validity of the model, we
reproduced in this article the exact experimental protocol of DiCarlo et al. that
has been used to examine the structure of receptive fields in area 3b of the
primary somatosensory cortex. Using the same analysis toolset, the model yields
consistent results, having most of the receptive fields to contain a single
region of excitation and one to several regions of inhibition. We further
proceeded our study using a dynamic competition that deeply influences the
formation of the receptive fields. We hypothesized this dynamic competition to
correspond to some form of somatosensory attention that may help to precisely
shape the receptive fields. To test this hypothesis, we designed a protocol where
an arbitrary region of interest is delineated on the index distal finger pad and
we either (1) instructed explicitly the model to attend to this region
(simulating an attentional signal) (2) preferentially trained the model on this
region or (3) combined the two aforementioned protocols simultaneously. Results
tend to confirm that dynamic competition leads to shrunken receptive fields and
its joint interaction with intensive training promotes a massive receptive fields
migration and shrinkage.
PMID- 25120462
TI - Associative learning of classical conditioning as an emergent property of
spatially extended spiking neural circuits with synaptic plasticity.
AB - Associative learning of temporally disparate events is of fundamental importance
for perceptual and cognitive functions. Previous studies of the neural mechanisms
of such association have been mainly focused on individual neurons or synapses,
often with an assumption that there is persistent neural firing activity that
decays slowly. However, experimental evidence supporting such firing activity for
associative learning is still inconclusive. Here we present a novel, alternative
account of associative learning in the context of classical conditioning,
demonstrating that it is an emergent property of a spatially extended, spiking
neural circuit with spike-timing dependent plasticity and short term synaptic
depression. We show that both the conditioned and unconditioned stimuli can be
represented by spike sequences which are produced by wave patterns propagating
through the network, and that the interactions of these sequences are timing
dependent. After training, the occurrence of the sequence encoding the
conditioned stimulus (CS) naturally regenerates that encoding the unconditioned
stimulus (US), therefore resulting in association between them. Such associative
learning based on interactions of spike sequences can happen even when the
timescale of their separation is significantly larger than that of individual
neurons. In particular, our network model is able to account for the temporal
contiguity property of classical conditioning, as observed in behavioral studies.
We further show that this emergent associative learning in our network model is
quite robust to noise perturbations. Our results therefore demonstrate that
associative learning of temporally disparate events can happen in a distributed
way at the level of neural circuits.
PMID- 25120463
TI - 1D-3D hybrid modeling-from multi-compartment models to full resolution models in
space and time.
AB - Investigation of cellular and network dynamics in the brain by means of modeling
and simulation has evolved into a highly interdisciplinary field, that uses
sophisticated modeling and simulation approaches to understand distinct areas of
brain function. Depending on the underlying complexity, these models vary in
their level of detail, in order to cope with the attached computational cost.
Hence for large network simulations, single neurons are typically reduced to time
dependent signal processors, dismissing the spatial aspect of each cell. For
single cell or networks with relatively small numbers of neurons, general purpose
simulators allow for space and time-dependent simulations of electrical signal
processing, based on the cable equation theory. An emerging field in
Computational Neuroscience encompasses a new level of detail by incorporating the
full three-dimensional morphology of cells and organelles into three-dimensional,
space and time-dependent, simulations. While every approach has its advantages
and limitations, such as computational cost, integrated and methods-spanning
simulation approaches, depending on the network size could establish new ways to
investigate the brain. In this paper we present a hybrid simulation approach,
that makes use of reduced 1D-models using e.g., the NEURON simulator-which
couples to fully resolved models for simulating cellular and sub-cellular
dynamics, including the detailed three-dimensional morphology of neurons and
organelles. In order to couple 1D- and 3D-simulations, we present a geometry-,
membrane potential- and intracellular concentration mapping framework, with which
graph- based morphologies, e.g., in the swc- or hoc-format, are mapped to full
surface and volume representations of the neuron and computational data from 1D
simulations can be used as boundary conditions for full 3D simulations and vice
versa. Thus, established models and data, based on general purpose 1D-simulators,
can be directly coupled to the emerging field of fully resolved, highly detailed
3D-modeling approaches. We present the developed general framework for 1D/3D
hybrid modeling and apply it to investigate electrically active neurons and their
intracellular spatio-temporal calcium dynamics.
PMID- 25120464
TI - Operant conditioning: a minimal components requirement in artificial spiking
neurons designed for bio-inspired robot's controller.
AB - In this paper, we investigate the operant conditioning (OC) learning process
within a bio-inspired paradigm, using artificial spiking neural networks (ASNN)
to act as robot brain controllers. In biological agents, OC results in behavioral
changes learned from the consequences of previous actions, based on progressive
prediction adjustment from rewarding or punishing signals. In a neurorobotics
context, virtual and physical autonomous robots may benefit from a similar
learning skill when facing unknown and unsupervised environments. In this work,
we demonstrate that a simple invariant micro-circuit can sustain OC in multiple
learning scenarios. The motivation for this new OC implementation model stems
from the relatively complex alternatives that have been described in the
computational literature and recent advances in neurobiology. Our elementary
kernel includes only a few crucial neurons, synaptic links and originally from
the integration of habituation and spike-timing dependent plasticity as learning
rules. Using several tasks of incremental complexity, our results show that a
minimal neural component set is sufficient to realize many OC procedures. Hence,
with the proposed OC module, designing learning tasks with an ASNN and a bio
inspired robot context leads to simpler neural architectures for achieving
complex behaviors.
PMID- 25120465
TI - Brain-computer interface-based robotic end effector system for wrist and hand
rehabilitation: results of a three-armed randomized controlled trial for chronic
stroke.
AB - The objective of this study was to investigate the efficacy of an
Electroencephalography (EEG)-based Motor Imagery (MI) Brain-Computer Interface
(BCI) coupled with a Haptic Knob (HK) robot for arm rehabilitation in stroke
patients. In this three-arm, single-blind, randomized controlled trial; 21
chronic hemiplegic stroke patients (Fugl-Meyer Motor Assessment (FMMA) score 10
50), recruited after pre-screening for MI BCI ability, were randomly allocated to
BCI-HK, HK or Standard Arm Therapy (SAT) groups. All groups received 18 sessions
of intervention over 6 weeks, 3 sessions per week, 90 min per session. The BCI-HK
group received 1 h of BCI coupled with HK intervention, and the HK group received
1 h of HK intervention per session. Both BCI-HK and HK groups received 120 trials
of robot-assisted hand grasping and knob manipulation followed by 30 min of
therapist-assisted arm mobilization. The SAT group received 1.5 h of therapist
assisted arm mobilization and forearm pronation-supination movements
incorporating wrist control and grasp-release functions. In all, 14 males, 7
females, mean age 54.2 years, mean stroke duration 385.1 days, with baseline FMMA
score 27.0 were recruited. The primary outcome measure was upper extremity FMMA
scores measured mid-intervention at week 3, end-intervention at week 6, and
follow-up at weeks 12 and 24. Seven, 8 and 7 subjects underwent BCI-HK, HK and
SAT interventions respectively. FMMA score improved in all groups, but no
intergroup differences were found at any time points. Significantly larger motor
gains were observed in the BCI-HK group compared to the SAT group at weeks 3, 12,
and 24, but motor gains in the HK group did not differ from the SAT group at any
time point. In conclusion, BCI-HK is effective, safe, and may have the potential
for enhancing motor recovery in chronic stroke when combined with therapist
assisted arm mobilization.
PMID- 25120467
TI - Sequential treatment of multiple actinic keratoses with solaraze and actikerall.
AB - Interest is increasing in the use of sequential or combined therapeutic
modalities for spot or area treatment of actinic keratoses (AKs) to achieve
complete sustained remission. For multiple lesions in a contained area, topical
treatment offers less discomfort, better cosmesis and greater patient convenience
than destructive/ablative techniques. Twelve patients with multiple grade I and
II AK lesions of the scalp (cases 1-10) or the dorsum of the hand (cases 11 and
12), most with a history of recurrence, were treated with Solaraze gel (3%
diclofenac sodium in 2.5% hyaluronic acid) twice daily for 12 weeks, followed by
a 2-week treatment-free interval, then Actikerall cutaneous solution (5
fluorouracil 5 mg/g and salicylic acid 100 mg/g) once daily for up to 6 weeks as
required. Sequential treatment provided complete (clinical and histological)
clearance in 8/10 male patients. Two patients with numerous lesions had partial
clearance (significant improvement) and the remaining few lesions were treated
with erbium laser. Both female patients achieved complete clinical clearance with
sequential treatment. Solaraze/Actikerall were well tolerated. A case of contact
dermatitis with Solaraze resolved after discontinuation and the patient
progressed to treatment with Actikerall. Local application site reactions
resolved upon treatment completion. Topical lesion-directed sequential treatment
with Solaraze/Actikerall is a rational approach to treat patients with multiple
AKs. Sequential treatment produces excellent clearance rates which are
accompanied by relevant improvement in patients' quality of life.
PMID- 25120468
TI - Keratoacanthoma accompanied by multiple lung squamous cell carcinomas developing
in a renal transplant recipient.
AB - Keratoacanthoma (KA) is a benign keratinocytic neoplasm that spontaneously
regresses after 3-6 months and shares features with well-differentiated squamous
cell carcinoma (SCC). An increased incidence of both KA and non-melanoma skin
tumor, including SCC, is seen among immunosuppressed, organ-transplant
recipients. In this report we describe a case of KA accompanied by multiple lung
SCCs developing in a renal transplant recipient.
PMID- 25120466
TI - Characterizing relationships of DTI, fMRI, and motor recovery in stroke
rehabilitation utilizing brain-computer interface technology.
AB - The relationship of the structural integrity of white matter tracts and cortical
activity to motor functional outcomes in stroke patients is of particular
interest in understanding mechanisms of brain structural and functional changes
while recovering from stroke. This study aims to probe these underlying
mechanisms using diffusion tensor imaging (DTI) and fMRI measures. We examined
the structural integrity of the posterior limb of the internal capsule (PLIC)
using DTI and corticomotor activity using motor-task fMRI in stroke patients who
completed up to 15 sessions of rehabilitation therapy using Brain-Computer
Interface (BCI) technology. We hypothesized that (1) the structural integrity of
PLIC and corticomotor activity are affected by stroke; (2) changes in structural
integrity and corticomotor activity following BCI intervention are related to
motor recovery; (3) there is a potential relationship between structural
integrity and corticomotor activity. We found that (1) the ipsilesional PLIC
showed significantly decreased fractional anisotropy (FA) values when compared to
the contralesional PLIC; (2) lower ipsilesional PLIC-FA values were significantly
associated with worse motor outcomes (i.e., ipsilesional PLIC-FA and motor
outcomes were positively correlated.); (3) lower ipsilesional PLIC-FA values were
significantly associated with greater ipsilesional corticomotor activity during
impaired-finger-tapping-task fMRI (i.e., ipsilesional PLIC-FA and ipsilesional
corticomotor activity were negatively correlated), with an overall bilateral
pattern of corticomotor activity observed; and (4) baseline FA values predicted
motor recovery assessed after BCI intervention. These findings suggest that (1)
greater vs. lesser microstructural integrity of the ipsilesional PLIC may
contribute toward better vs. poor motor recovery respectively in the stroke
affected limb and demand lesser vs. greater cortical activity respectively from
the ipsilesional motor cortex; and that (2) PLIC-FA is a promising biomarker in
tracking and predicting motor functional recovery in stroke patients receiving
BCI intervention.
PMID- 25120469
TI - Rothmund-thomson syndrome: a 13-year follow-up.
AB - Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder presenting
with poikiloderma and other clinical features, affecting the bones and eyes and,
in type II RTS, presenting an increased risk for malignancy. With about 300 cases
reported so far, we present a 13-year follow-up including clinical images, X-rays
and genetic analysis. A 13-month-old female started with a facial rash with
blisters on her cheeks and limbs at the age of 3 months along with congenital
hypoplastic thumbs, frontal bossing and fine hair, eyebrows and eyelashes. The
patient was lost to follow-up and returned 12 years later with palmoplantar
hyperkeratotic lesions, short stature, disseminated poikiloderma and sparse scalp
hair, with absence of eyelashes and eyebrows. Radiographic analysis showed radial
ray defect, absence of the thumb and three wrist carpal bones, and reduced bone
density. Gene sequencing for the RECQL4 helicase gene revealed a mutation on each
allele. RTS is a rare disease, and in this patient we observed the evolution of
her skin lesions and other clinical features, which were important for the
classification of type II RTS. The next years will provide even more information
on this rare disease.
PMID- 25120470
TI - Primary Duodenal Adenocarcinoma without Stenosis: A Case Report with a Brief
Literature Review.
AB - This article focuses on the symptomatic and diagnostic problems of primary
duodenal adenocarcinoma (PDA) by way of two case reports and a literature review.
An 85-year-old woman with an adenocarcinoma in the 1st duodenal portion was
offered palliative care. A 90-year-old woman with an adenocarcinoma in the 3rd
duodenal portion was also offered palliative care. A unique finding in the two
cases reported herein is that PDA did not cause stenosis and occlusion of the
lumen. As no reports of PDA without stenosis have been published so far, these
cases may add to our knowledge of PDA. The diagnosis of PDA is often delayed
because its symptoms may be absent until the tumor has progressed, thus leading
to a delay of several months. Patients typically present with a long history of
variable and vague symptoms, and many are diagnosed with advanced disease. As
regards clinical manifestations, abdominal pain is the most frequent symptom. The
majority of these tumors are found to have infiltrated the duodenal wall at
presentation, with many being unresectable due to local and distal invasion.
Esophagogastroduodenoscopy and gastrointestinal barium radiography are the main
diagnostic tests for PDA, detecting 88.6 and 83.3% of tumors, respectively. In
some cases, ultrasonography or computed tomography are useful for detecting PDA
and determining vascular invasion.
PMID- 25120471
TI - Use of Core Needle Biopsy rather than Fine-Needle Aspiration Cytology in the
Diagnostic Approach of Breast Cancer.
AB - BACKGROUND AND AIMS: In the following study case, we reviewed breast ultrasound
guided core needle biopsy (CNB), using Mammotome (vacuum-assisted breast biopsy)
and Tru-cut, carried out on palpable and nonpalpable uncertain breast lumps or
malignant large lesions to be submitted to neoadjuvant chemotherapy. MATERIAL AND
METHODS: Examinations were conducted during a 4-year period of clinical activity
in a highly specialized center, from December 2009 to December 2013, in 712
patients previously subjected to fine-needle aspiration cytology (FNAC). RESULTS:
The results demonstrated that among the 712 breast biopsies, in many cases FNAC
was not conclusive, and therefore we proceeded with the echo-guided biopsy,
through which we were able to collect sufficient material for the histological
examination in order to direct patients to surgery or follow-up. CONCLUSIONS: CNB
is far superior to FNAC, especially in cases of uncertainty, where it is
preferable to proceed directly with CNB, which may also determine additional
prognostic and predictive markers. Initially FNAC is less expensive, but the
actual costs involved tend to be higher for FNAC as it is less accurate and a CNB
is often required. In accordance with recent publications, we can confirm the
full validity of CNB in the diagnostic approach of breast lesions.
PMID- 25120473
TI - Severe dermatologic reactions with bendamustine: a case series.
AB - Cutaneous drug reactions make up the largest proportion of adverse events in the
medical field. Causality, in particular, is difficult to determine, and
therefore, preventing recurrent reactions can be challenging. Bendamustine was
initially thought to be a well-tolerated chemotherapy agent with few side effects
aside from bone marrow suppression. However, the incidence of cutaneous reactions
reported is rising. We describe three such reactions in relation to bendamustine
administration in hopes of adding to the awareness of such side effects.
PMID- 25120472
TI - Horrifying Basal cell carcinoma: cytological, immunohistochemical, and
ultrastructural findings.
AB - Basal cell carcinoma (BCC) is a slow-growing and frequently occurring tumor of
the eyelids. Among BCC cases, there is a subtype of aggressive cases called
horrifying BCC (HBCC). There are also rare BCC cases that show neuroendocrine
differentiation. Here, we describe a case of HBCC with neuroendocrine
differentiation. The patient, a 41-year-old woman, presented with abnormal left
eye tearing and left cheek pain. On computed tomography imaging, a tumor that
extended to the left orbit was detected in the left cheek. On cytological
examination of fine-needle aspiration (FNA) samples, the tumor cells were
observed as sheet-like clusters and single bare nuclei with a clear background;
peripheral palisading was not clearly seen. On examination of the biopsy specimen
taken after FNA, the tumor was found to be composed of cancer cell nests with
scattered peripheral palisading in the dermis. Immunohistochemically, the tumor
cells were positive for cytokeratin (CK) 7 and CD56 and were negative for CK20,
synaptophysin, and chromogranin A. Membrane-bound dense-core granules were
detected on ultrastructural study. A HBCC case with neuroendocrine
differentiation has not been previously reported. The correlation between the
presence of neuroendocrine differentiation in HBCC and patient prognosis should
be further studied.
PMID- 25120474
TI - Massive bilateral serous retinal detachment in a case of hypertensive
chorioretinopathy.
AB - INTRODUCTION: Systemic high blood pressure is related to a variety of retinal
manifestations. We present an atypical case of hypertensive chorioretinopathy
with massive bilateral serous retinal detachment. CASE REPORT: A 26-year-old male
with a genitourinary malformation and secondary grade IV chronic kidney failure
as well as high blood pressure complained of acute vision loss. Dilated fundus
examination evidenced a bilateral serous retinal detachment with macular
involvement. The patient was unresponsive to oral antihypertensive therapy and
dialysis treatment. The serous retinal detachment progressively decreased after
the restoration of dialysis and antihypertensive therapy. The final visual acuity
was 0.50 in both eyes. DISCUSSION: In cases of serous macular detachment, it is
mandatory to rule out different systemic and ocular diseases. The presence of
uncontrolled high blood pressure may produce aggressive bilateral retinal
changes, thus hypertension must be under early and strict control in order to
improve the visual outcomes.
PMID- 25120475
TI - Swept-source optical coherence tomographic findings of choroidal osteoma.
AB - PURPOSE: To report the morphologic features of a choroidal osteoma using swept
source optical coherence tomography (SS-OCT) and fundus autofluorescence (FAF).
METHODS: Two eyes of two cases with a choroidal osteoma were studied using SS-OCT
and FAF. RESULTS: The location of the tumor was circumpapillary without macular
involvement in case 1 and juxtapapillary with macular involvement in case 2. Both
cases had a mixture of calcified and decalcified areas, and a concomitant
choroidal neovascularization was found in case 2. The FAF images showed decreased
autofluorescence in the central decalcified regions and relatively preserved
fluorescence in marginal calcified regions in both cases. SS-OCT revealed a
normal inner retina and an abnormal outer retina in both cases, and subretinal
fluid in case 2. The calcified regions appeared sponge-like and were multilayered
in case 2. A lamellar reflective pattern was observed in the decalcified regions
in case 1, and hyperreflective mound-like areas were observed in both cases. SS
OCT demonstrated hyperreflective areas above Bruch's membrane accompanied by
disruption of Bruch's membrane in case 1. The chorioscleral border was visible in
both cases. CONCLUSIONS: The FAF pattern in the calcified and decalcified areas
of the choroidal osteoma may correspond to the different stage of tumor
evolution. The SS-OCT findings indicate that choroidal osteomas can have
characteristic reflective patterns and alterations of the overlying retina.
PMID- 25120476
TI - Systemic inflammation, blood-brain barrier vulnerability and cognitive/non
cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy.
AB - The incidence of dementia is increasing at an alarming rate, and has become a
major public health concern. Alzheimer disease (AD) is the most common form of
dementia and is characterized by progressive cognitive impairment. In addition to
classical neuropathological features such as amyloid plaques and neurofibrillary
tangles (NFT), accumulation of activated immune cells has been documented in the
AD brain, suggesting a contribution of neuroinflammation in the pathogenesis of
AD. Besides cognitive deterioration, non-cognitive symptoms, such as agitation,
aggression, depression and psychosis, are often observed in demented patients,
including those with AD, and these neuropsychological symptoms place a heavy
burden on caregivers. These symptoms often exhibit sudden onset and tend to
fluctuate over time, and in many cases, they are triggered by an infection in
peripheral organs, suggesting that inflammation plays an important role in the
pathogenesis of these non-cognitive symptoms. However, there is no mechanistic
explanation for the relationship between inflammation and neuropsychiatric
symptoms. Observations from experimental mouse models indicate that alteration of
brain blood vessels, especially blood-brain barrier (BBB) dysfunction, may
contribute to the relationship. The current review summarizes the results from
recent studies on the relationship between inflammation and AD, while focusing on
cerebrovascular alterations, which might provide an insight into the pathogenesis
of cognitive/non-cognitive symptoms in AD patients and suggest a basis for the
development of new therapeutic treatments for these conditions.
PMID- 25120479
TI - Inflammatory nociception responses do not vary with age, but diminish with the
pain history.
AB - Some of the relevant factors that must be considered when dealing with old age
include its growing numbers in the general population and pain contention in this
age group. In this sense, it is important to study whether antinociceptive
responses change with age. To elucidate this point, persistent pain in animals is
the preferred model. In addition, the response to inflammatory pain in the same
individual must be explored along its lifetime. Male Wistar rats were infiltrated
with carrageenan (50 MUl intraplantar) and tested 3 h and 24 h after injection
using thermal (plantar test) and mechanociceptive tests (von Frey). The rats were
divided into the following groups: (a) young rats infiltrated for the first time
at 12 weeks of age and re-infiltrated at 15 and 17 weeks; (b) adult rats
infiltrated for the first time at 28 weeks of age and re-infiltrated at 44 and 56
weeks; and (c) old rats infiltrated for the first time at 56 weeks of age and re
infiltrated at 72 weeks. The rats tested for the first time at 12 and 56 weeks of
age showed hyperalgesia due to carrageenan infiltration at 3 h and 24 h after
injection. This result showed that old rats maintain the same antialgesic
response due to inflammation. However, when the injection was repeated in the
three age groups, the latency to the thermal and mechanociceptive responses at 3
h is increased when compared to animals exposed for the first time to
inflammation. The response to thermal and mechanociception in old rats is the
same as in young animals as long as the nociceptive stimulus is not repeated. The
repetition of the stimulus produces changes compatible with desensitization of
the response and evidences the significance of algesic stimulus repetition in the
same individual rather than the age of the individual.
PMID- 25120478
TI - Effects of combined MAO-B inhibitors and levodopa vs. monotherapy in Parkinson's
disease.
AB - BACKGROUND: Prior studies report that monoamine oxidases inhibitors (MAO-I) when
used as an adjunct to levodopa ameliorate motor symptoms in Parkinson's disease
(PD), but this was not tested in relation to cognitive or psychiatric measures.
OBJECTIVE: Here, we tested the effects of MAO-I as an adjunct to levodopa, in
comparison to levodopa or dopamine (DA) agonists alone, on various cognitive,
affective and quality of life measures. METHODS: We studied three groups of
subjects: healthy controls, PD patients on combined levodopa and MAO-I, and PD
patients on levodopa or DA agonists only. RESULTS: We found that compared to
monotherapy, combined MAO-I and levodopa seemed to improve cognition, including
probabilistic learning, working memory and executive functions. There were no
differences between the different medication regimes on deterministic learning,
attention or memory recall. It was also found that MAO-I as an adjunct to
levodopa improves affective measures such as depression, apathy, anxiety and
quality of life. Interestingly, this enhancing effect of combined levodopa and
MAO-I was more pronounced in PD patients with severe akinesia, compared to
patients with severe tremor. CONCLUSION: Our data are in agreement with (a) the
Continuous Dopaminergic Stimulation (CDS) theory which states that continuous
stimulation of the basal ganglia enhances motor, psychiatric and cognitive
functions in PD patients; and/or (b) findings that MAO-I increase the
bioavailability of monoamines that have beneficial effects on motor and
behavioral dysfunction in PD.
PMID- 25120480
TI - Graph analysis of verbal fluency test discriminate between patients with
Alzheimer's disease, mild cognitive impairment and normal elderly controls.
AB - Verbal fluency is the ability to produce a satisfying sequence of spoken words
during a given time interval. The core of verbal fluency lies in the capacity to
manage the executive aspects of language. The standard scores of the semantic
verbal fluency test are broadly used in the neuropsychological assessment of the
elderly, and different analytical methods are likely to extract even more
information from the data generated in this test. Graph theory, a mathematical
approach to analyze relations between items, represents a promising tool to
understand a variety of neuropsychological states. This study reports a graph
analysis of data generated by the semantic verbal fluency test by cognitively
healthy elderly (NC), patients with Mild Cognitive Impairment-subtypes amnestic
(aMCI) and amnestic multiple domain (a+mdMCI)-and patients with Alzheimer's
disease (AD). Sequences of words were represented as a speech graph in which
every word corresponded to a node and temporal links between words were
represented by directed edges. To characterize the structure of the data we
calculated 13 speech graph attributes (SGA). The individuals were compared when
divided in three (NC-MCI-AD) and four (NC-aMCI-a+mdMCI-AD) groups. When the three
groups were compared, significant differences were found in the standard measure
of correct words produced, and three SGA: diameter, average shortest path, and
network density. SGA sorted the elderly groups with good specificity and
sensitivity. When the four groups were compared, the groups differed
significantly in network density, except between the two MCI subtypes and NC and
aMCI. The diameter of the network and the average shortest path were
significantly different between the NC and AD, and between aMCI and AD. SGA
sorted the elderly in their groups with good specificity and sensitivity,
performing better than the standard score of the task. These findings provide
support for a new methodological frame to assess the strength of semantic memory
through the verbal fluency task, with potential to amplify the predictive power
of this test. Graph analysis is likely to become clinically relevant in neurology
and psychiatry, and may be particularly useful for the differential diagnosis of
the elderly.
PMID- 25120477
TI - Alzheimer's disease: relevant molecular and physiopathological events affecting
amyloid-beta brain balance and the putative role of PPARs.
AB - Alzheimer's disease (AD) is the most common form of age-related dementia. With
the expected aging of the human population, the estimated morbidity of AD
suggests a critical upcoming health problem. Several lines of research are
focused on understanding AD pathophysiology, and although the etiology of the
disease remains a matter of intense debate, increased brain levels of amyloid
beta (Abeta) appear to be a critical event in triggering a wide range of
molecular alterations leading to AD. It has become evident in recent years that
an altered balance between production and clearance is responsible for the
accumulation of brain Abeta. Moreover, Abeta clearance is a complex event that
involves more than neurons and microglia. The status of the blood-brain barrier
(BBB) and choroid plexus, along with hepatic functionality, should be considered
when Abeta balance is addressed. Furthermore, it has been proposed that exposure
to sub-toxic concentrations of metals, such as copper, could both directly affect
these secondary structures and act as a seeding or nucleation core that
facilitates Abeta aggregation. Recently, we have addressed peroxisomal
proliferator-activated receptors (PPARs)-related mechanisms, including the direct
modulation of mitochondrial dynamics through the PPARgamma-coactivator-1alpha
(PGC-1alpha) axis and the crosstalk with critical aging- and neurodegenerative
related cellular pathways. In the present review, we revise the current knowledge
regarding the molecular aspects of Abeta production and clearance and provide a
physiological context that gives a more complete view of this issue.
Additionally, we consider the different structures involved in AD-altered Abeta
brain balance, which could be directly or indirectly affected by a nuclear
receptor (NR)/PPAR-related mechanism.
PMID- 25120482
TI - Sarcopenia and physical frailty: two sides of the same coin.
PMID- 25120481
TI - Amylin and its analogs: a friend or foe for the treatment of Alzheimer's disease?
AB - Amylin, a gut-brain axis hormone, and amyloid-beta peptides (Abeta), a major
component of the Alzheimer's disease (AD) brain, share several features,
including similar beta-sheet secondary structures, binding to the same receptor
and being degraded by the same protease, insulin degrading enzyme (IDE). However,
while amylin readily crosses the blood brain barrier (BBB) and mediates several
activities including improving glucose metabolism, relaxing cerebrovascular
structure, modulating inflammatory reaction and perhaps enhancing neural
regeneration, Abeta has no known physiological functions. Thus, abundant Abeta in
the AD brain could block or interfere with the binding of amylin to its receptor
and hinder its functions. Recent studies using animal models for AD demonstrate
that amylin and its analog reduce the AD pathology in the brain and improve
cognitive impairment in AD. Given that, in addition to amyloid plaques and
neurofibrillary tangles, perturbed cerebral glucose metabolism and
cerebrovascular damage are the hallmarks of the AD brain, we propose that giving
exogenous amylin type peptides have the potential to become a new avenue for the
diagnosis and therapeutic of AD. Although amylin's property of self-aggregation
may be a limitation to developing it as a therapeutic for AD, its clinical
analog, pramlintide containing 3 amino acid differences from amylin, does not
aggregate like human amylin, but more potently mediates amylin's activities in
the brain. Pramlintide is an effective drug for diabetes with a favorable profile
of safety. Thus a randomized, double-blind, placebo-controlled clinical trial
should be conducted to examine the efficacy of pramlintide for AD. This review
summarizes the knowledge and findings on amylin type peptides and discuss pros
and cons for their potential for AD.
PMID- 25120484
TI - From industrial research to academic discoveries, toward a new concept of
partnership: the Biomathics model.
PMID- 25120483
TI - Relationships between Personality Traits, Medial Temporal Lobe Atrophy, and White
Matter Lesion in Subjects Suffering from Mild Cognitive Impairment.
AB - Mild cognitive impairment (MCI) is a heterogeneous cognitive status that can be a
prodromal stage of Alzheimer's disease (AD). It is particularly relevant to focus
on prodromal stages of AD such as MCI, because patho-physiological abnormalities
of AD start years before the dementia stage. Medial temporal lobe (MTL) atrophy
resulting from AD lesions and cerebrovascular lesions [i.e., white matter lesions
(WML), lacunar strokes, and strokes] are often revealed concurrently on magnetic
resonance imaging (MRI) in MCI subjects. Personality changes have been reported
to be associated with MCI status and early AD. More specifically, an increase in
neuroticism and a decrease in conscientiousness have been reported, suggesting
that higher and lower scores, respectively, in neuroticism and conscientiousness
are associated with an increased risk of developing the disease. However,
personality changes have not been studied concomitantly with pathological
structural brain alterations detected on MRI in patients suffering from MCI.
Therefore, the objective of the present study was to assess the relationship
between MTL atrophy, WML, lacunar strokes, and personality traits in such
patients. The severity of WML was strongly associated with lower levels of
conscientiousness and higher levels of neuroticism. Conversely, no association
was detected between personality traits and the presence of lacunar strokes or
MTL atrophy. Altogether, these results strongly suggest that personality changes
occurring in a MCI population, at high risk of AD, are associated with WML, which
can induce executive dysfunctions, rather than with MTL atrophy.
PMID- 25120485
TI - Implementation of pharmacokinetic and pharmacodynamic strategies in early
research phases of drug discovery and development at Novartis Institute of
Biomedical Research.
AB - Characterizing the relationship between the pharmacokinetics (PK, concentration
vs. time) and pharmacodynamics (PD, effect vs. time) is an important tool in the
discovery and development of new drugs in the pharmaceutical industry. The
purpose of this publication is to serve as a guide for drug discovery scientists
toward optimal design and conduct of PK/PD studies in the research phase. This
review is a result of the collaborative efforts of DMPK scientists from various
Metabolism and Pharmacokinetic (MAP) departments of the global organization
Novartis Institute of Biomedical Research (NIBR). We recommend that PK/PD
strategies be implemented in early research phases of drug discovery projects to
enable successful transition to drug development. Effective PK/PD study design,
analysis, and interpretation can help scientists elucidate the relationship
between PK and PD, understand the mechanism of drug action, and identify PK
properties for further improvement and optimal compound design. Additionally,
PK/PD modeling can help increase the translation of in vitro compound potency to
the in vivo setting, reduce the number of in vivo animal studies, and improve
translation of findings from preclinical species into the clinical setting. This
review focuses on three important elements of successful PK/PD studies, namely
partnership among key scientists involved in the study execution; parameters that
influence study designs; and data analysis and interpretation. Specific examples
and case studies are highlighted to help demonstrate key points for
consideration. The intent is to provide a broad PK/PD foundation for colleagues
in the pharmaceutical industry and serve as a tool to promote appropriate
discussions on early research project teams with key scientists involved in PK/PD
studies.
PMID- 25120486
TI - The IRP/IRE system in vivo: insights from mouse models.
AB - Iron regulatory proteins 1 and 2 (IRP1 and IRP2) post-transcriptionally control
the expression of several mRNAs encoding proteins of iron, oxygen and energy
metabolism. The mechanism involves their binding to iron responsive elements
(IREs) in the untranslated regions of target mRNAs, thereby controlling mRNA
translation or stability. Whereas IRP2 functions solely as an RNA-binding
protein, IRP1 operates as either an RNA-binding protein or a cytosolic aconitase.
Early experiments in cultured cells established a crucial role of IRPs in
regulation of cellular iron metabolism. More recently, studies in mouse models
with global or localized Irp1 and/or Irp2 deficiencies uncovered new
physiological functions of IRPs in the context of systemic iron homeostasis.
Thus, IRP1 emerged as a key regulator of erythropoiesis and iron absorption by
controlling hypoxia inducible factor 2alpha (HIF2alpha) mRNA translation, while
IRP2 appears to dominate the control of iron uptake and heme biosynthesis in
erythroid progenitor cells by regulating the expression of transferrin receptor 1
(TfR1) and 5-aminolevulinic acid synthase 2 (ALAS2) mRNAs, respectively. Targeted
disruption of either Irp1 or Irp2 in mice is associated with distinct phenotypic
abnormalities. Thus, Irp1(-/-) mice develop polycythemia and pulmonary
hypertension, while Irp2(-/-) mice present with microcytic anemia, iron overload
in the intestine and the liver, and neurologic defects. Combined disruption of
both Irp1 and Irp2 is incombatible with life and leads to early embryonic
lethality. Mice with intestinal- or liver-specific disruption of both Irps are
viable at birth but die later on due to malabsorption or liver failure,
respectively. Adult mice lacking both Irps in the intestine exhibit a profound
defect in dietary iron absorption due to a "mucosal block" that is caused by the
de-repression of ferritin mRNA translation. Herein, we discuss the physiological
function of the IRE/IRP regulatory system.
PMID- 25120487
TI - Drug elucidation: invertebrate genetics sheds new light on the molecular targets
of CNS drugs.
AB - Many important drugs approved to treat common human diseases were discovered by
serendipity, without a firm understanding of their modes of action. As a result,
the side effects and interactions of these medications are often unpredictable,
and there is limited guidance for improving the design of next-generation drugs.
Here, we review the innovative use of simple model organisms, especially
Caenorhabditis elegans, to gain fresh insights into the complex biological
effects of approved CNS medications. Whereas drug discovery involves the
identification of new drug targets and lead compounds/biologics, and drug
development spans preclinical testing to FDA approval, drug elucidation refers to
the process of understanding the mechanisms of action of marketed drugs by
studying their novel effects in model organisms. Drug elucidation studies have
revealed new pathways affected by antipsychotic drugs, e.g., the insulin
signaling pathway, a trace amine receptor and a nicotinic acetylcholine receptor.
Similarly, novel targets of antidepressant drugs and lithium have been identified
in C. elegans, including lipid-binding/transport proteins and the SGK-1 signaling
pathway, respectively. Elucidation of the mode of action of anesthetic agents has
shown that anesthesia can involve mitochondrial targets, leak currents, and gap
junctions. The general approach reviewed in this article has advanced our
knowledge about important drugs for CNS disorders and can guide future drug
discovery efforts.
PMID- 25120489
TI - Analysis of co-assembly and co-localization of ameloblastin and amelogenin.
AB - Epithelially-derived ameloblasts secrete extracellular matrix proteins including
amelogenin, enamelin, and ameloblastin. Complex intermolecular interactions among
these proteins are believed to be important in controlling enamel formation. Here
we provide in vitro and in vivo evidence of co-assembly and co-localization of
ameloblastin with amelogenin using both biophysical and immunohistochemical
methods. We performed co-localization studies using immunofluorescence confocal
microscopy with paraffin-embedded tissue sections from mandibular molars of mice
at 1, 5, and 8 days of age. Commercially-available ameloblastin antibody (M300)
against mouse ameloblastin residues 107-407 and an antibody against full-length
recombinant mouse (rM179) amelogenin were used. Ameloblastin-M300 clearly reacted
along the secretory face of ameloblasts from days 1-8. Quantitative co
localization was analyzed (QCA) in several configurations by choosing appropriate
regions of interest (ROIs). Analysis of ROIs along the secretory face of
ameloblasts revealed that at day 1, very high percentages of both the
ameloblastin and amelogenin co-localized. At day 8 along the ameloblast cells the
percentage of co-localization remained high for the ameloblastin whereas co
localization percentage was reduced for amelogenin. Analysis of the entire
thickness on day 8 revealed no significant co-localization of amelogenin and
ameloblastin. With the progress of amelogenesis and ameloblastin degradation,
there was a segregation of ameloblastin and co-localization with the C-terminal
region decreased. CD spectra indicated that structural changes in ameloblastin
occurred upon addition of amelogenin. Our data suggest that amelogenin
ameloblastin complexes may be the functional entities at the early stage of
enamel mineralization.
PMID- 25120490
TI - Comparison of two mouse ameloblast-like cell lines for enamel-specific gene
expression.
AB - Ameloblasts are ectoderm-derived cells that produce an extracellular enamel
matrix that mineralizes to form enamel. The development and use of immortalized
cell lines, with a stable phenotype, is an important contribution to biological
studies as it allows for the investigation of molecular activities without the
continuous need for animals. In this study we compare the expression profiles of
enamel-specific genes in two mouse derived ameloblast-like cell lines: LS8 and
ALC cells. Quantitative PCR analysis indicates that, relative to each other, LS8
cells express greater mRNA levels for genes that define secretory-stage
activities (Amelx, Ambn, Enam, and Mmp20), while ALC express greater mRNA levels
for genes that define maturation-stage activities (Odam and Klk4). Western blot
analyses show that Amelx, Ambn, and Odam proteins are detectable in ALC, but not
LS8 cells. Unstimulated ALC cells form calcified nodules, while LS8 cells do not.
These data provide greater insight as to the suitability of both cell lines to
contribute to biological studies on enamel formation and biomineralization, and
highlight some of the strengths and weaknesses when relying on enamel epithelial
organ-derived cell lines to study molecular activities of amelogenesis.
PMID- 25120488
TI - Nano-scale measurement of biomolecules by optical microscopy and semiconductor
nanoparticles.
AB - Over the past decade, great developments in optical microscopy have made this
technology increasingly compatible with biological studies. Fluorescence
microscopy has especially contributed to investigating the dynamic behaviors of
live specimens and can now resolve objects with nanometer precision and
resolution due to super-resolution imaging. Additionally, single particle
tracking provides information on the dynamics of individual proteins at the
nanometer scale both in vitro and in cells. Complementing advances in microscopy
technologies has been the development of fluorescent probes. The quantum dot, a
semi-conductor fluorescent nanoparticle, is particularly suitable for single
particle tracking and super-resolution imaging. This article overviews the
principles of single particle tracking and super resolution along with describing
their application to the nanometer measurement/observation of biological systems
when combined with quantum dot technologies.
PMID- 25120491
TI - Need for multi-scale systems to identify spindle orientation regulators relevant
to tissue disorganization in solid cancers.
PMID- 25120493
TI - Sympathetic dysfunction in vasovagal syncope and the postural orthostatic
tachycardia syndrome.
AB - Orthostatic intolerance is the inability to tolerate the upright posture and is
relieved by recumbence. It most commonly affects young women and has a major
impact on quality of life and psychosocial well-being. Several forms of
orthostatic intolerance have been described. The most common one is the recurrent
vasovagal syncope (VVS) phenotype which presents as a transient and abrupt loss
of consciousness and postural tone that is followed by rapid recovery. Another
common type of orthostatic intolerance is the postural orthostatic tachycardia
syndrome (POTS) which is characterized by an excessive rise in heart rate upon
standing and is associated with symptoms of presyncope such as light-headedness,
fatigue, palpitations, and nausea. Maintenance of arterial pressure under
condition of reduced central blood volume during the orthostasis is accomplished
in large part through sympathetic efferent nerve traffic to the peripheral
vasculature. Therefore sympathetic nervous system (SNS) dysfunction is high on
the list of possible contributors to the pathophysiology of orthostatic
intolerance. Investigations into the role of the SNS in orthostatic intolerance
have yielded mixed results. This review outlines the current knowledge of the
function of the SNS in both VVS and POTS.
PMID- 25120495
TI - Can exercise increase fitness and reduce weight in patients with schizophrenia
and depression?
AB - BACKGROUND: Psychiatric patients have a reduced life expectancy of 15-20 years
compared with the general population. Most years of lost life are due to the
excess mortality from somatic diseases. Sedentary lifestyle and medication is
partly responsible for the high frequency of metabolic syndrome in this patient
group and low levels of physical activity is associated with increased risk of
cardiovascular disease, diabetes, and all-cause mortality. This study aimed to
review trials allocating patients with either schizophrenia or depression to
exercise interventions for effect on cardiovascular fitness, strength, and
weight. METHODS: We searched PubMed, Embase, and PsycINFO including randomized
clinical trial allocating patients with either schizophrenia or depression to
isolated exercise interventions. RESULTS: We identified five trials including
patients with schizophrenia (n = 94) and found little evidence that exercise
could increase cardiovascular fitness or decrease weight. Nine exercise trials
for patients with depression (n = 892) were identified increasing cardiovascular
fitness by 11-30% and strength by 33-37%. No evidence in favor of exercise for
weight reduction was found. CONCLUSION: Based on the current evidence isolated
exercise interventions are unlikely to improve cardiovascular fitness or induce
weight loss in patients with schizophrenia. In patients with depression, exercise
interventions are likely to induce clinically relevant short term effects,
however, due to lack of reporting, little is known about the effect on weight
reduction and cardiovascular fitness. Future exercise trials regarding patients
with mental illness should preferably measure changes in cardiovascular strength,
repetition maximum, and anthropometric outcomes. Ideally, participants should be
assessed beyond the intervention to identify long lasting effects.
PMID- 25120492
TI - Plasmacytoid dendritic cells: development, functions, and role in atherosclerotic
inflammation.
AB - Plasmacytoid dendritic cells (pDCs) are a specialized subset of DCs that links
innate and adaptive immunity. They sense viral and bacterial pathogens and
release high levels of Type I interferons (IFN-I) in response to infection. pDCs
were shown to contribute to inflammatory responses in the steady state and in
pathology. In atherosclerosis, pDCs are involved in priming vascular inflammation
and atherogenesis through production of IFN-I and chemokines that attract
inflammatory cells to inflamed sites. pDCs also contribute to the proinflammatory
activation of effector T cells, cytotoxic T cells, and conventional DCs. However,
tolerogenic populations of pDCs are found that suppress atherosclerosis
associated inflammation through down-regulation of function and proliferation of
proinflammatory T cell subsets and induction of regulatory T cells with potent
immunomodulatory properties. Notably, atheroprotective tolerogenic DCs could be
induced by certain self-antigens or bacterial antigens that suggests for great
therapeutic potential of these DCs for development of DC-based anti-atherogenic
vaccines.
PMID- 25120494
TI - Tenascin-C and mechanotransduction in the development and diseases of
cardiovascular system.
AB - Living tissue is composed of cells and extracellular matrix (ECM). In the heart
and blood vessels, which are constantly subjected to mechanical stress, ECM
molecules form well-developed fibrous frameworks to maintain tissue structure.
ECM is also important for biological signaling, which influences various cellular
functions in embryonic development, and physiological/pathological responses to
extrinsic stimuli. Among ECM molecules, increased attention has been focused on
matricellular proteins. Matricellular proteins are a growing group of non
structural ECM proteins highly up-regulated at active tissue remodeling, serving
as biological mediators. Tenascin-C (TNC) is a typical matricellular protein,
which is highly expressed during embryonic development, wound healing,
inflammation, and cancer invasion. The expression is tightly regulated, dependent
on the microenvironment, including various growth factors, cytokines, and
mechanical stress. In the heart, TNC appears in a spatiotemporal-restricted
manner during early stages of development, sparsely detected in normal adults,
but transiently re-expressed at restricted sites associated with tissue injury
and inflammation. Similarly, in the vascular system, TNC is strongly up-regulated
during embryonic development and under pathological conditions with an increase
in hemodynamic stress. Despite its intriguing expression pattern, cardiovascular
system develops normally in TNC knockout mice. However, deletion of TNC causes
acute aortic dissection (AAD) under strong mechanical and humoral stress.
Accumulating reports suggest that TNC may modulate the inflammatory response and
contribute to elasticity of the tissue, so that it may protect cardiovascular
tissue from destructive stress responses. TNC may be a key molecule to control
cellular activity during development, adaptation, or pathological tissue
remodeling.
PMID- 25120496
TI - Trophic Mechanisms for Exercise-Induced Stress Resilience: Potential Role of
Interactions between BDNF and Galanin.
AB - Current concepts of the neurobiology of stress-related disorders, such as anxiety
and depression emphasize disruptions in neural plasticity and neurotrophins. The
potent trophic actions of exercise, therefore, represent not only an effective
means for prevention and treatment of these disorders, they also afford the
opportunity to employ exercise paradigms as a basic research tool to uncover the
neurobiological mechanisms underlying these disorders. Novel approaches to
studying stress-related disorders focus increasingly on trophic factor signaling
in corticolimbic circuits that both mediate and regulate cognitive, behavioral,
and physiological responses to deleterious stress. Recent evidence demonstrates
that the neural plasticity supported by these trophic mechanisms is vital for
establishing and maintaining resilience to stress. Therapeutic interventions that
promote these mechanisms, be they pharmacological, behavioral, or environmental,
may therefore prevent or reverse stress-related mental illness by enhancing
resilience. The present paper will provide an overview of trophic mechanisms
responsible for the enhancement of resilience by voluntary exercise with an
emphasis on brain-derived neurotrophic factor, galanin, and interactions between
these two trophic factors.
PMID- 25120497
TI - Timing and time perception: A selective review and commentary on recent reviews.
PMID- 25120499
TI - Testing strong factorial invariance using three-level structural equation
modeling.
AB - Within structural equation modeling, the most prevalent model to investigate
measurement bias is the multigroup model. Equal factor loadings and intercepts
across groups in a multigroup model represent strong factorial invariance
(absence of measurement bias) across groups. Although this approach is possible
in principle, it is hardly practical when the number of groups is large or when
the group size is relatively small. Jak et al. (2013) showed how strong factorial
invariance across large numbers of groups can be tested in a multilevel
structural equation modeling framework, by treating group as a random instead of
a fixed variable. In the present study, this model is extended for use with three
level data. The proposed method is illustrated with an investigation of strong
factorial invariance across 156 school classes and 50 schools in a Dutch
dyscalculia test, using three-level structural equation modeling.
PMID- 25120500
TI - Is there an inverted-U relationship between creativity and psychopathology?
PMID- 25120498
TI - The role of arousal in the spontaneous regulation of emotions in healthy aging: a
fMRI investigation.
AB - Despite ample support for enhanced affective well-being and emotional stability
in healthy aging, the role of potentially important dimensions, such as the
emotional arousal, has not been systematically investigated in neuroimaging
studies. In addition, the few behavioral studies that examined effects of arousal
have produced inconsistent findings. The present study manipulated the arousal of
pictorial stimuli to test the hypothesis that preserved emotional functioning in
aging is modulated by the level of arousal, and to identify the associated neural
correlates. Young and older healthy participants were presented with negative and
neutral pictures, which they rated for emotional content, while fMRI data were
recorded. There were three main novel findings regarding the neural mechanisms
underlying the processing of negative pictures with different levels of arousal
in young and older adults. First, the common engagement of the right amygdala in
young and older adults was driven by high arousing negative stimuli. Second,
complementing an age-related reduction in the subjective ratings for low arousing
negative pictures, there were opposing patterns of activity in the
rostral/ventral anterior cingulate cortex (ACC) and the amygdala, which showed
increased vs. decreased responses, respectively, to low arousing negative
pictures. Third, increased spontaneous activity in the ventral ACC/ventromedial
prefrontal cortex (vmPFC) in older adults was linked to reduced ratings for low
arousing negative pictures. Overall, these findings advance our understanding of
the neural correlates underlying processing of negative emotions with different
levels of arousal in the context of enhanced emotional functioning in healthy
aging. Notably, the results support the idea that older adults have emotion
regulation networks chronically activated, in the absence of explicit induction
of the goal to regulate emotions, and that this effect is specific to low
arousing negative emotions.
PMID- 25120501
TI - Error management for musicians: an interdisciplinary conceptual framework.
AB - Musicians tend to strive for flawless performance and perfection, avoiding errors
at all costs. Dealing with errors while practicing or performing is often
frustrating and can lead to anger and despair, which can explain musicians'
generally negative attitude toward errors and the tendency to aim for flawless
learning in instrumental music education. But even the best performances are
rarely error-free, and research in general pedagogy and psychology has shown that
errors provide useful information for the learning process. Research in
instrumental pedagogy is still neglecting error issues; the benefits of risk
management (before the error) and error management (during and after the error)
are still underestimated. It follows that dealing with errors is a key aspect of
music practice at home, teaching, and performance in public. And yet, to be
innovative, or to make their performance extraordinary, musicians need to risk
errors. Currently, most music students only acquire the ability to manage errors
implicitly - or not at all. A more constructive, creative, and differentiated
culture of errors would balance error tolerance and risk-taking against error
prevention in ways that enhance music practice and music performance. The
teaching environment should lay the foundation for the development of such an
approach. In this contribution, we survey recent research in aviation, medicine,
economics, psychology, and interdisciplinary decision theory that has
demonstrated that specific error-management training can promote metacognitive
skills that lead to better adaptive transfer and better performance skills. We
summarize how this research can be applied to music, and survey-relevant research
that is specifically tailored to the needs of musicians, including generic
guidelines for risk and error management in music teaching and performance. On
this basis, we develop a conceptual framework for risk management that can
provide orientation for further music education and musicians at all levels.
PMID- 25120502
TI - Parallel effects of memory set activation and search on timing and working memory
capacity.
AB - Accurately estimating a time interval is required in everyday activities such as
driving or cooking. Estimating time is relatively easy, provided a person attends
to it. But a brief shift of attention to another task usually interferes with
timing. Most processes carried out concurrently with timing interfere with it.
Curiously, some do not. Literature on a few processes suggests a general
proposition, the Timing and Complex-Span Hypothesis: A process interferes with
concurrent timing if and only if process performance is related to complex span.
Complex-span is the number of items correctly recalled in order, when each item
presented for study is followed by a brief activity. Literature on task
switching, visual search, memory search, word generation and mental time travel
supports the hypothesis. Previous work found that another process, activation of
a memory set in long term memory, is not related to complex-span. If the Timing
and Complex-Span Hypothesis is true, activation should not interfere with
concurrent timing in dual-task conditions. We tested such activation in single
task memory search task conditions and in dual-task conditions where memory
search was executed with concurrent timing. In Experiment 1, activating a memory
set increased reaction time, with no significant effect on time production. In
Experiment 2, set size and memory set activation were manipulated. Activation and
set size had a puzzling interaction for time productions, perhaps due to
difficult conditions, leading us to use a related but easier task in Experiment
3. In Experiment 3 increasing set size lengthened time production, but memory
activation had no significant effect. Results here and in previous literature on
the whole support the Timing and Complex-Span Hypotheses. Results also support a
sequential organization of activation and search of memory. This organization
predicts activation and set size have additive effects on reaction time and
multiplicative effects on percent correct, which was found.
PMID- 25120503
TI - Using Bayes to get the most out of non-significant results.
AB - No scientific conclusion follows automatically from a statistically non
significant result, yet people routinely use non-significant results to guide
conclusions about the status of theories (or the effectiveness of practices). To
know whether a non-significant result counts against a theory, or if it just
indicates data insensitivity, researchers must use one of: power, intervals (such
as confidence or credibility intervals), or else an indicator of the relative
evidence for one theory over another, such as a Bayes factor. I argue Bayes
factors allow theory to be linked to data in a way that overcomes the weaknesses
of the other approaches. Specifically, Bayes factors use the data themselves to
determine their sensitivity in distinguishing theories (unlike power), and they
make use of those aspects of a theory's predictions that are often easiest to
specify (unlike power and intervals, which require specifying the minimal
interesting value in order to address theory). Bayes factors provide a coherent
approach to determining whether non-significant results support a null hypothesis
over a theory, or whether the data are just insensitive. They allow accepting and
rejecting the null hypothesis to be put on an equal footing. Concrete examples
are provided to indicate the range of application of a simple online Bayes
calculator, which reveal both the strengths and weaknesses of Bayes factors.
PMID- 25120505
TI - Measuring the crowd within again: a pre-registered replication study.
AB - According to the crowd within effect, the average of two estimates from one
person tends to be more accurate than a single estimate of that person. The
effect implies that the well documented wisdom of the crowd effect-the crowd's
average estimate tends to be more accurate than the individual estimates-can be
obtained within a single individual. In this paper, we performed a high-powered,
pre-registered replication study of the original experiment. Our replication
results are evaluated with the traditional null hypothesis significance testing
approach, as well as with effect sizes and their confidence intervals. We adopted
a co-pilot approach, in the sense that all analyses were performed independently
by two researchers using different analysis software. Moreover, we report Bayes
factors for all tests. We successfully replicated the crowd within effect, both
when the second guess was made immediately after the first guess, as well as when
it was made 3 weeks later. The experimental protocol, the raw data, the post
processed data and the analysis code are available online.
PMID- 25120507
TI - The role of both parents' attachment pattern in understanding childhood obesity.
AB - Within the research area on the determinants of childhood obesity, a relatively
new approach is the use of attachment theory to explore the mechanisms underlying
children's obesity risk, especially considered as emotion regulation strategies
in parent-child relationship. Few are the empirical researches that have
addressed this issue. The empirical investigations have used self-report measures
to assess adult attachment. In attachment studies, the use of interview methods
and/or performance-based instruments is advised to evaluate the entire range of
possible adult attachment patterns and comprehensively explain the emotional
strategies, correlates, and consequences of individual differences in attachment
system functioning. The aim of this study was to explore the extent to which both
parents' attachment patterns serve as self-regulative mechanisms related to
childhood overweight/obesity by the Adult Attachment Projective Picture System
(AAP) in a sample of 44 mothers and fathers of children referred for obesity.
Insecure attachment was found as a risk factor both for mothers and fathers. Also
unresolved/disorganization was found to play a significant role in childhood
obesity. The role of father's attachment was explored and findings suggested
considering it in etiology and treatment of childhood obesity.
PMID- 25120506
TI - Musicians are more consistent: Gestural cross-modal mappings of pitch, loudness
and tempo in real-time.
AB - Cross-modal mappings of auditory stimuli reveal valuable insights into how humans
make sense of sound and music. Whereas researchers have investigated cross-modal
mappings of sound features varied in isolation within paradigms such as speeded
classification and forced-choice matching tasks, investigations of
representations of concurrently varied sound features (e.g., pitch, loudness and
tempo) with overt gestures-accounting for the intrinsic link between movement and
sound-are scant. To explore the role of bodily gestures in cross-modal mappings
of auditory stimuli we asked 64 musically trained and untrained participants to
represent pure tones-continually sounding and concurrently varied in pitch,
loudness and tempo-with gestures while the sound stimuli were played. We
hypothesized musical training to lead to more consistent mappings between pitch
and height, loudness and distance/height, and tempo and speed of hand movement
and muscular energy. Our results corroborate previously reported pitch vs. height
(higher pitch leading to higher elevation in space) and tempo vs. speed
(increasing tempo leading to increasing speed of hand movement) associations, but
also reveal novel findings pertaining to musical training which influenced
consistency of pitch mappings, annulling a commonly observed bias for convex
(i.e., rising-falling) pitch contours. Moreover, we reveal effects of
interactions between musical parameters on cross-modal mappings (e.g., pitch and
loudness on speed of hand movement), highlighting the importance of studying
auditory stimuli concurrently varied in different musical parameters. Results are
discussed in light of cross-modal cognition, with particular emphasis on studies
within (embodied) music cognition. Implications for theoretical refinements and
potential clinical applications are provided.
PMID- 25120508
TI - Emotion and affect in mental imagery: do fear and anxiety manipulate mental
rotation performance?
AB - Little is known about the effects of fear as a basic emotion on mental rotation
(MR) performance. We expected that the emotional arousal evoked by fearful
stimuli presented prior to each MR trial would enhance MR performance. Regarding
the influence of anxiety, high anxious participants are supposed to show slower
responses and higher error rates in this specific visuo-spatial ability.
Furthermore, with respect to the embodied cognition viewpoint we wanted to
investigate if the influence of fear on MR performance is the same for egocentric
and object-based transformations. To investigate this, we presented either
negative or neutral images prior to each MR trial. Participants were allocated to
the specific emotion in a randomized order. Results show that fear enhances MR
performance, expressed by a higher MR speed. Interestingly, this influence is
dependent on the type of transformation: it is restricted to egocentric
rotations. Both observation of emotional stimuli and egocentric strategies are
associated with left hemisphere activation which could explain a stronger
influence on this type of transformation during observation. Another possible
notion is the conceptual link between visuo-spatial perspective taking and
empathy based on the co-activation of parietal areas. Stronger responses in
egocentric transformations could result from this specific link. Regarding the
influence of anxiety, participants with high scores on the trait-anxiety scale
showed poor results in both reaction time and MR speed. Findings of impoverished
recruitment of prefrontal attentional control in patients with high scores in
trait anxiety could be the explanation for this reduced performance.
PMID- 25120509
TI - Visual appearance interacts with conceptual knowledge in object recognition.
AB - Objects contain rich visual and conceptual information, but do these two types of
information interact? Here, we examine whether visual and conceptual information
interact when observers see novel objects for the first time. We then address how
this interaction influences the acquisition of perceptual expertise. We used two
types of novel objects (Greebles), designed to resemble either animals or tools,
and two lists of words, which described non-visual attributes of people or man
made objects. Participants first judged if a word was more suitable for
describing people or objects while ignoring a task-irrelevant image, and showed
faster responses if the words and the unfamiliar objects were congruent in terms
of animacy (e.g., animal-like objects with words that described human).
Participants then learned to associate objects and words that were either
congruent or not in animacy, before receiving expertise training to rapidly
individuate the objects. Congruent pairing of visual and conceptual information
facilitated observers' ability to become a perceptual expert, as revealed in a
matching task that required visual identification at the basic or subordinate
levels. Taken together, these findings show that visual and conceptual
information interact at multiple levels in object recognition.
PMID- 25120511
TI - Psychotherapy participants show increased physiological responsiveness to a lab
stressor relative to matched controls.
AB - Accumulating evidence indicates that psychotherapy participants show increased
physiological responsiveness to stress. The purpose of the present study was to
examine differences between individuals participating in outpatient psychotherapy
and matched controls using an experimental design. Forty-two psychotherapy
participants and 48 matched controls were assessed on cardiovascular and cortisol
functioning at baseline, during the Trier Social Stress Test (TSST), and during a
20-min recovery period. Psychotherapy participants and matched controls did not
differ at baseline or during the TSST on the physiological measures but
psychotherapy participants had higher cortisol and heart rate (HR) during the
recovery period. In regards to reactivity, cortisol increased during the recovery
period for the psychotherapy participants but decreased for those in the matched
control group. Psychotherapy participants experiencing clinically significant
levels of distress displayed elevated systolic and diastolic blood pressure and
HR during the TSST when compared to psychotherapy participants not experiencing
clinically significant levels of distress. Overall, physiological reactivity to
stress appears to be an important issue for those in psychotherapy and directly
addressing this issue may help improve psychotherapy outcomes.
PMID- 25120510
TI - Multi-domain computerized cognitive training program improves performance of
bookkeeping tasks: a matched-sampling active-controlled trial.
AB - Cognitive skills are important predictors of job performance, but the extent to
which computerized cognitive training (CCT) can improve job performance in
healthy adults is unclear. We report, for the first time, that a CCT program
aimed at attention, memory, reasoning and visuo-spatial abilities can enhance
productivity in healthy younger adults on bookkeeping tasks with high relevance
to real-world job performance. 44 business students (77.3% female, mean age 21.4
+/- 2.6 years) were assigned to either (a) 20 h of CCT, or (b) 20 h of
computerized arithmetic training (active control) by a matched sampling
procedure. Both interventions were conducted over a period of 6 weeks, 3-4 1-h
sessions per week. Transfer of skills to performance on a 60-min paper-based
bookkeeping task was measured at three time points-baseline, after 10 h and after
20 h of training. Repeated measures ANOVA found a significant Group X Time effect
on productivity (F = 7.033, df = 1.745; 73.273, p = 0.003) with a significant
interaction at both the 10-h (Relative Cohen's effect size = 0.38, p = 0.014) and
20-h time points (Relative Cohen's effect size = 0.40, p = 0.003). No significant
effects were found on accuracy or on Conners' Continuous Performance Test, a
measure of sustained attention. The results are discussed in reference to
previous findings on the relationship between brain plasticity and job
performance. Generalization of results requires further study.
PMID- 25120512
TI - A holistic intervention program for children from low socioeconomic status
families.
PMID- 25120504
TI - Elucidating unconscious processing with instrumental hypnosis.
AB - Most researchers leverage bottom-up suppression to unlock the underlying
mechanisms of unconscious processing. However, a top-down approach - for example
via hypnotic suggestion - paves the road to experimental innovation and
complementary data that afford new scientific insights concerning attention and
the unconscious. Drawing from a reliable taxonomy that differentiates subliminal
and preconscious processing, we outline how an experimental trajectory that
champions top-down suppression techniques, such as those practiced in hypnosis,
is uniquely poised to further contextualize and refine our scientific
understanding of unconscious processing. Examining subliminal and preconscious
methods, we demonstrate how instrumental hypnosis provides a reliable adjunct
that supplements contemporary approaches. Specifically, we provide an integrative
synthesis of the advantages and shortcomings that accompany a top-down approach
to probe the unconscious mind. Our account provides a larger framework for
complementing the results from core studies involving prevailing subliminal and
preconscious techniques.
PMID- 25120514
TI - Singing and social inclusion.
AB - There is a growing body of neurological, cognitive, and social psychological
research to suggest the possibility of positive transfer effects from structured
musical engagement. In particular, there is evidence to suggest that engagement
in musical activities may impact on social inclusion (sense of self and of being
socially integrated). Tackling social exclusion and promoting social inclusion
are common concerns internationally, such as in the UK and the EC, and there are
many diverse Government ministries and agencies globally that see the arts in
general and music in particular as a key means by which social needs can be
addressed. As part of a wider evaluation of a national, Government-sponsored
music education initiative for Primary-aged children in England ("Sing Up"),
opportunity was taken by the authors, at the request of the funders, to assess
any possible relationship between (a) children's developing singing behavior and
development and (b) their social inclusion (sense of self and of being socially
integrated). Subsequently, it was possible to match data from n = 6087
participants, drawn from the final 3 years of data collection (2008-2011), in
terms of each child's individually assessed singing ability (based on their
singing behavior of two well-known songs to create a "normalized singing score")
and their written responses to a specially-designed questionnaire that included a
set of statements related to children's sense of being socially included to which
the children indicated their level of agreement on a seven-point Likert scale.
Data analyses suggested that the higher the normalized singing development
rating, the more positive the child's self-concept and sense of being socially
included, irrespective of singer age, sex and ethnicity.
PMID- 25120517
TI - Intersubjectivity and interaction as crucial for understanding the moral role of
shame: a critique of TOSCA-based shame research.
PMID- 25120515
TI - The body and the fading away of abstract concepts and words: a sign language
analysis.
AB - One of the most important challenges for embodied and grounded theories of
cognition concerns the representation of abstract concepts, such as "freedom."
Many embodied theories of abstract concepts have been proposed. Some proposals
stress the similarities between concrete and abstract concepts showing that they
are both grounded in perception and action system while other emphasize their
difference favoring a multiple representation view. An influential view proposes
that abstract concepts are mapped to concrete ones through metaphors.
Furthermore, some theories underline the fact that abstract concepts are grounded
in specific contents, as situations, introspective states, emotions. These
approaches are not necessarily mutually exclusive, since it is possible that they
can account for different subsets of abstract concepts and words. One novel and
fruitful way to understand the way in which abstract concepts are represented is
to analyze how sign languages encode concepts into signs. In the present paper we
will discuss these theoretical issues mostly relying on examples taken from
Italian Sign Language (LIS, Lingua dei Segni Italiana), the visual-gestural
language used within the Italian Deaf community. We will verify whether and to
what extent LIS signs provide evidence favoring the different theories of
abstract concepts. In analyzing signs we will distinguish between direct forms of
involvement of the body and forms in which concepts are grounded differently, for
example relying on linguistic experience. In dealing with the LIS evidence, we
will consider the possibility that different abstract concepts are represented
using different levels of embodiment. The collected evidence will help us to
discuss whether a unitary embodied theory of abstract concepts is possible or
whether the different theoretical proposals can account for different aspects of
their representation.
PMID- 25120516
TI - On the interrelation between reduced lateralization, schizotypy, and creativity.
PMID- 25120513
TI - Hits and misses: leveraging tDCS to advance cognitive research.
AB - The popularity of non-invasive brain stimulation techniques in basic, commercial,
and applied settings grew tremendously over the last decade. Here, we focus on
one popular neurostimulation method: transcranial direct current stimulation
(tDCS). Many assumptions regarding the outcomes of tDCS are based on the results
of stimulating motor cortex. For instance, the primary motor cortex is
predictably suppressed by cathodal tDCS or made more excitable by anodal tDCS.
However, wide-ranging studies testing cognition provide more complex and
sometimes paradoxical results that challenge this heuristic. Here, we first
summarize successful efforts in applying tDCS to cognitive questions, with a
focus on working memory (WM). These recent findings indicate that tDCS can result
in cognitive task improvement or impairment regardless of stimulation site or
direction of current flow. We then report WM and response inhibition studies that
failed to replicate and/or extend previously reported effects. From these
opposing outcomes, we present a series of factors to consider that are intended
to facilitate future use of tDCS when applied to cognitive questions. In short,
common pitfalls include testing too few participants, using insufficiently
challenging tasks, using heterogeneous participant populations, and including
poorly motivated participants. Furthermore, the poorly understood underlying
mechanism for long-lasting tDCS effects make it likely that other important
factors predict responses. In conclusion, we argue that although tDCS can be used
experimentally to understand brain function its greatest potential may be in
applied or translational research.
PMID- 25120518
TI - Role-play facilitates children's mindreading of those with atypical color
perception.
AB - The present study examined the effects of role-play experience on children's
mindreading ability. Forty-one primary school children (20 boys, 21 girls, mean
age: 9.37 years, range: 8-11 years) were introduced to a communication task in
which the use of mindreading was essential. During each trial, participants
viewed a shelf, presented on a laptop, which contained several familiar objects,
and they were instructed to touch an object on the shelf following an order
issued by a "manager" who stood at the opposite side of the shelf. There were two
managers: one was a monkey manager with normal color vision, and the other was a
dog manager with restricted color vision. The monkey manager could see all the
objects in the same colors as the participants, whereas the dog manager saw some
objects in different colors. Participants were required to respond according to
the manager's instruction. In the restricted color vision condition, the dog
manager saw the colors of objects differently; thus, participants had to work out
his intentions, according to his different perspective. In the normal color
vision condition, all objects were in the same colors as those seen by the monkey
manager. Before the test phase, participants in the role-play group were provided
a role-play experience in which they assumed the role of the dog manager with
restricted color vision. The experimental data were analyzed using a 2 * 2 mixed
design ANOVA (role-play condition * communication partner condition) to examine
differences in the error rate. Both main effects and its interaction were
significant. According to the post-hoc analyses, participants in the no-role-play
condition made significantly more errors in the restricted color vision condition
than in the normal color vision condition, whereas no such difference was found
among participants in the role-play condition. These results suggest that role
play experience could facilitate mindreading of characters with restricted color
vision.
PMID- 25120519
TI - A fan effect in anaphor processing: effects of multiple distractors.
AB - Research suggests that the presence of a non-referent from the same category as
the referent interferes with anaphor resolution. In five experiments, the
hypothesis that multiple non-referents would produce a cumulative interference
effect (i.e., a fan effect) was examined. This hypothesis was supported in
Experiments 1A and 1B, with subjects being less accurate and slower to recognize
referents (1A) and non-referents (1B) as the number of potential referents
increased from two to five. Surprisingly, the number of potential referents led
to a decrease in anaphor reading times. The results of Experiments 2A and 2B
replicated the probe-recognition results in a completely within-subjects design
and ruled out the possibility that a speeded-reading strategy led to the fan
effect findings. The results of Experiment 3 provided evidence that subjects were
resolving the anaphors. These results suggest that multiple non-referents do
produce a cumulative interference effect; however, additional research is
necessary to explore the effect on anaphor reading times.
PMID- 25120520
TI - Responsibility problems for criminal justice.
PMID- 25120522
TI - Movement induced tremor in musicians and non-musicians reflects adaptive brain
plasticity.
AB - Evidence exists that motor dexterity is associated with a higher tremor amplitude
of physiological tremor. Likewise, lower frequencies are associated with motor
control. So far only case reports of a higher amplitude of physiological tremor
in musicians exist. Moreover, no study has investigated lower frequencies during
a finger movement task in musicians who can be regarded as a model of motor
expertise. We developed a model and derived three hypotheses which we
investigated in this study: (1) Tremor amplitude is higher in the range of
physiological tremor and (2) higher for frequency ranges of dystonic tremor in
musicians compared to non-musicians; (3) there is no difference in tremor
amplitude at frequencies below 4 Hz. We measured tremor during a finger flexion
extension movement in 19 musicians (age 26.5 +/- 8.2 years) and 24 age matched
non-musicians (age 26.5 +/- 8.7). By using empirical mode decomposition in
combination with a Hilbert transform we obtained the instantaneous frequency and
amplitude, allowing to compare tremor amplitudes throughout the movement at
various frequency ranges. We found a significantly higher tremor amplitude in
musicians for physiological tremor and a tendency toward a higher amplitude
during most of the movement in the frequency range of 4-8 Hz, which, however, was
not significant. No difference was found in the frequency range below 4 Hz for
the flexion and for almost the entire extension movement. Our results corroborate
findings that the 8-12 Hz oscillatory activity plays a role in motor dexterity.
However, our results do not allow for the conclusion that tremor at the frequency
range of 4-8 Hz is related to either plasticity induced changes that are
beneficial for motor skill development nor to maladaptive changes as, e.g., focal
dystonia.
PMID- 25120521
TI - The emergence of human prosociality: aligning with others through feelings,
concerns, and norms.
AB - The fact that humans cooperate with nonkin is something we take for granted, but
this is an anomaly in the animal kingdom. Our species' ability to behave
prosocially may be based on human-unique psychological mechanisms. We argue here
that these mechanisms include the ability to care about the welfare of others
(other-regarding concerns), to "feel into" others (empathy), and to understand,
adhere to, and enforce social norms (normativity). We consider how these
motivational, emotional, and normative substrates of prosociality develop in
childhood and emerged in our evolutionary history. Moreover, we suggest that
these three mechanisms all serve the critical function of aligning individuals
with others: Empathy and other-regarding concerns align individuals with one
another, and norms align individuals with their group. Such alignment allows us
to engage in the kind of large-scale cooperation seen uniquely in humans.
PMID- 25120523
TI - Age-related changes in the temporal dynamics of executive control: a study in 5-
and 6-year-old children.
AB - Based on the Dual Mechanisms of Control theory (Braver et al., 2007), this study
conducted in 5- and 6-year-olds, tested for a possible shift between two modes of
control, proactive vs. reactive, which differ in the way goal information is
retrieved and maintained in working memory. To this end, we developed a children
adapted version of the AX-Continuous-Performance Task (AX-CPT). Twenty-nine 5
year-olds and 28-6-year-olds performed the task in both low and high working
memory load conditions (corresponding, respectively, to a short and a long cue
probe delay). Analyses suggested that a qualitative change in the mode of control
occurs within the 5-year-old group. However, quantitative, more graded changes
were also observed both within the 5-year-olds, and between 5 and 6 years of age.
These graded changes demonstrated an increasing efficiency in proactive control
with age. The increase in working memory load did not impact the type of dynamics
of control, but had a detrimental effect on sensitivity to cue information. These
findings highlight that the development of the temporal dynamics of control can
be characterized by a shift from reactive to proactive control together with a
more protracted and gradual improvement in the efficiency of proactive control.
Moreover, the question of whether the observed shift in the mode of control is
task dependant is debated.
PMID- 25120524
TI - AT1 receptor blockade alters nutritional and biometric development in obesity
resistant and obesity-prone rats submitted to a high fat diet.
AB - Obesity is a chronic metabolic condition with important public health
implications associated with numerous co-morbidities including cardiovascular
disease, insulin resistance, and hypertension. The renin angiotensin system
(RAS), best known for its involvement in cardiovascular control and body fluid
homeostasis has, more recently, been implicated in regulation of energy balance.
Interference with the RAS (genetically or pharmacologically) has been shown to
influence body weight gain. In this study we investigated the effects of systemic
AT1 receptor blockade using losartan on ingestive behaviors and weight gain in
diet induced obese (DIO) rats. Prior to losartan administration (30 mg/kg/day)
body weight gain remained constant within the DIO animals (3.6 +/- 0.3 g/day, n =
8), diet resistant (DR) animals (2.1 +/- 0.6 g/day, n = 8) and in the age-matched
chow fed control (CHOW) animals (2.8 +/- 0.3 g/day, n = 8), Losartan
administration abolished body weight gain in animals fed a high fat diet (DIO:
0.4 +/- 0.7 g/day, n = 8; and DR: -0.8 +/- 0.3 g/day, n = 8) while chow fed
animals continued to gain weight (2.2 +/- 0.3 g/day, n = 8) as they had
previously to oral administration of losartan. This decrease in daily body weight
gain was accompanied by a decrease in food intake in the HFD fed animals.
Following the removal of losartan, both the DIO and DR animals again showed daily
increases in body weight gain and food intake which were similar to control
values. Our data demonstrate that oral losartan administration attenuates body
weight gain in animals fed a HFD whether the animal is obese (DIO) or not DR
while having no effect on body weight gain in age-matched chow fed animals
suggesting a protective effect of losartan against body weight gain while on a
HFD.
PMID- 25120525
TI - Colors, colored overlays, and reading skills.
AB - In this article, we are concerned with the role of colors in reading written
texts. It has been argued that colored overlays applied above written texts
positively influence both reading fluency and reading speed. These effects would
be particularly evident for those individuals affected by the so called Meares
Irlen syndrome, i.e., who experience eyestrain and/or visual distortions - e.g.,
color, shape, or movement illusions - while reading. This condition would
interest the 12-14% of the general population and up to the 46% of the dyslexic
population. Thus, colored overlays have been largely employed as a remedy for
some aspects of the difficulties in reading experienced by dyslexic individuals,
as fluency and speed. Despite the wide use of colored overlays, how they exert
their effects has not been made clear yet. Also, according to some researchers,
the results supporting the efficacy of colored overlays as a tool for helping
readers are at least controversial. Furthermore, the very nature of the Meares
Irlen syndrome has been questioned. Here we provide a concise, critical review of
the literature.
PMID- 25120526
TI - Selectivity in early prosocial behavior.
AB - Prosocial behavior requires expenditure of personal resources for the benefit of
others, a fact that creates a "problem" when considering the evolution of
prosociality. Models that address this problem have been developed, with emphasis
typically placed on reciprocity. One model considers the advantages of being
selective in terms of one's allocation of prosocial behavior so as to improve the
chance that one will be benefitted in return. In this review paper, we first
summarize this "partner choice" model and then focus on prosocial development in
the preschool years, where we make the case for selective partner choice in early
instances of human prosocial behavior.
PMID- 25120527
TI - Effects of distraction on memory and cognition: a commentary.
AB - This commentary is a review of the findings and ideas reported in the preceding
nine articles on the effects of distraction on aspects of cognitive performance.
The articles themselves deal with the disruptive effects of distraction on recall
of words, objects and events, also on visual processing, category formation and
other cognitive tasks. The commentary assesses the part played by "domain
general" suppression of distracting information and the "domain-specific"
competition arising when tasks and distraction involve very similar material.
Some forms of distraction are meaningfully relevant to the ongoing task, and
Treisman's (1964) model of selective attention is invoked to provide an account
of findings in this area. Finally, individual differences to vulnerability to
distraction are discussed; older adults are particularly affected by distracting
stimuli although the failure to repress distraction can sometimes prove
beneficial to later cognitive performance.
PMID- 25120528
TI - In the jungle of time: the concept of identity as a way out.
AB - WHAT COULD BE A UNIFYING PRINCIPLE FOR THE MANIFOLD OF TEMPORAL EXPERIENCES: the
simultaneity or temporal order of events, the subjective present, the duration of
experiences, or the impression of a continuity of time? Furthermore, we time
travel to the past visiting in imagination previous experiences in episodic
memory, and we also time travel to the future anticipating actions or plans. For
such time traveling we divide time into three domains: past, present, and future.
What could be an escape out of this "jungle of time" characterized by many
different perceptual and conceptual phenomena? The key concept we want to propose
is "identity" which is derived from homeostasis as a fundamental biological
principle. Within this conceptual frame two modes of identity are distinguished:
individual or self-identity required because of homeostatic demands, and object
related identity necessary for the reliability and efficiency of neuro-cognitive
processing. With this concept of self- and object-identity, the different
temporal experiences can be conceptualized within a common frame. Thus, we
propose a fundamental biological principle to conceptually unify temporal
phenomena on the psychological level.
PMID- 25120529
TI - Eye movement measurement in diagnostic assessment of disorders of consciousness.
AB - We review the literature to appraise the evidence supporting or disputing the use
of eye movement measurement in disorders of consciousness (DOC) with low levels
of arousal or awareness, such as minimally conscious state (MCS), vegetative
state (VS), and coma for diagnostic and prognostic purposes. We will focus on the
effectiveness of each technique in the diagnostic classification of these
patients and the gradual trend in research from manual to computerized tracking
methods. New tools have become available at clinicians' disposal to assess eye
movements with high spatial and temporal fidelity. The close relationship between
eye movement generation and organic dysfunction in the brain allows these tools
to be applied to the assessment of severe DOC as a unique supplementary toolset.
We posit that eye tracking can improve clinical diagnostic precision for DOC, a
key component of assessment that often dictates the course of clinical care in
DOC patients. We see the emergence of long-term eye-tracking studies with
seamless integration of technology in the future to improve the performance of
clinical assessment in DOC.
PMID- 25120530
TI - Developmental dynamics of radial vulnerability in the cerebral compartments in
preterm infants and neonates.
AB - The developmental vulnerability of different classes of axonal pathways in
preterm white matter is not known. We propose that laminar compartments of the
developing cerebral wall serve as spatial framework for axonal growth and
evaluate potential of anatomical landmarks for understanding reorganization of
the cerebral wall after perinatal lesions. The 3-T MRI (in vivo) and histological
analysis were performed in a series of cases ranging from 22 postconceptional
weeks to 3 years. For the follow-up scans, three groups of children (control,
normotypic, and preterms with lesions) were examined at the term equivalent age
and after the first year of life. MRI and histological abnormalities were
analyzed in the following compartments: (a) periventricular, with periventricular
fiber system; (b) intermediate, with periventricular crossroads, sagittal strata,
and centrum semiovale; (c) superficial, composed of gyral white matter, subplate,
and cortical plate. Vulnerability of thalamocortical pathways within the
crossroads and sagittal strata seems to be characteristic for early preterms,
while vulnerability of long association pathways in the centrum semiovale seems
to be predominant feature of late preterms. The structural indicator of the
lesion of the long association pathways is the loss of delineation between
centrum semiovale and subplate remnant, which is possible substrate of the
diffuse periventricular leukomalacia. The enhanced difference in MR signal
intensity of centrum semiovale and subplate remnant, observed in damaged children
after first year, we interpret as structural plasticity of intact short cortico
cortical fibers, which grow postnatally through U-zones and enter the cortex
through the subplate remnant. Our findings indicate that radial distribution of
MRI signal abnormalities in the cerebral compartments may be related to lesion of
different classes of axonal pathways and have prognostic value for predicting the
likely outcome of prenatal and perinatal lesions.
PMID- 25120532
TI - Higher TNF-alpha, IGF-1, and Leptin Levels are Found in Tasters than Non-Tasters.
AB - Taste perception is controlled by taste cells that are present in the tongue that
produce and secrete various metabolic hormones. Recent studies have demonstrated
that taste receptors in tongue, gut, and pancreas are associated with local
hormone secretion. The aim of this study was to determine whether there is a link
between taste sensitivity and levels of circulating metabolic hormones in humans
and whether taste sensitivity is potentially related to peripheral metabolic
regulation. Thirty-one subjects were recruited and separated into tasters and non
tasters based on their phenol thiocarbamide (PTC) bitter taste test results.
Fasting plasma and saliva were collected and levels of hormones and cytokines
were assayed. We observed significant differences in both hormone levels and
hormone-body mass index (BMI) correlation between tasters and non-tasters.
Tasters had higher plasma levels of leptin (p = 0.05), tumor necrosis factor
alpha (TNF-alpha) (p = 0.04), and insulin-like growth factor 1 (IGF-1) (p =
0.03). There was also a trend toward increased IGF-1 levels in the saliva of
tasters (p = 0.06). We found a positive correlation between plasma levels of
glucose and BMI (R = 0.4999, p = 0.04) exclusively in non-tasters. In contrast,
plasma C-peptide levels were found to be positively correlated to BMI (R =
0.5563, p = 0.03) in tasters. Saliva TNF-alpha levels were negatively correlated
with BMI in tasters (R = -0.5908, p = 0.03). Our findings demonstrate that there
are differences in circulating levels of leptin, TNF-alpha, and IGF-1 between
tasters and non-tasters. These findings indicate that in addition to the
regulation of food consumption, taste perception also appears to be tightly
linked to circulating metabolic hormone levels. People with different taste
sensitivity may respond differently to the nutrient stimulation. Further work
investigating the link between taste perception and peripheral metabolic control
could potentially lead to the development of novel therapies for obesity or Type
2 diabetes.
PMID- 25120533
TI - Inter-species interconnections in acid mine drainage microbial communities.
AB - Metagenomic studies are revolutionizing our understanding of microbes in the
biosphere. They have uncovered numerous proteins of unknown function in tens of
essentially unstudied lineages that lack cultivated representatives. Notably, few
of these microorganisms have been visualized, and even fewer have been described
ultra-structurally in their essentially intact, physiologically relevant states.
Here, we present cryogenic transmission electron microscope (cryo-TEM) 2D images
and 3D tomographic datasets for archaeal species from natural acid mine drainage
(AMD) microbial communities. Ultrastructural findings indicate the importance of
microbial interconnectedness via a range of mechanisms, including direct
cytoplasmic bridges and pervasive pili. The data also suggest a variety of
biological structures associated with cell-cell interfaces that lack explanation.
Some may play roles in inter-species interactions. Interdependences amongst the
archaea may have confounded prior isolation efforts. Overall, the findings
underline knowledge gaps related to archaeal cell components and highlight the
likely importance of co-evolution in shaping microbial lineages.
PMID- 25120531
TI - Estrogens and stem cells in thyroid cancer.
AB - Recent discoveries highlight the emerging role of estrogens in the initiation and
progression of different malignancies through their interaction with stem cell
(SC) compartment. Estrogens play a relevant role especially for those tumors
bearing a gender disparity in incidence and aggressiveness, as occurs for most
thyroid diseases. Although several experimental lines suggest that estrogens
promote thyroid cell proliferation and invasion, their precise contribution in SC
compartment still remains unclear. This review underlines the interplay between
hormones and thyroid function, which could help to complete the puzzle of gender
discrepancy in thyroid malignancies. Defining the association between estrogen
receptors' status and signaling pathways by which estrogens exert their effects
on thyroid cells is a potential tool that provides important insights in
pathogenetic mechanisms of thyroid tumors.
PMID- 25120534
TI - Effect of sulfate on low-temperature anaerobic digestion.
AB - The effect of sulfate addition on the stability of, and microbial community
behavior in, low-temperature anaerobic expanded granular sludge bed-based
bioreactors was investigated at 15 degrees C. Efficient bioreactor performance
was observed, with chemical oxygen demand (COD) removal efficiencies of >90%, and
a mean SO(2-) 4 removal rate of 98.3%. In situ methanogensis appeared unaffected
at a COD: SO(2-) 4 influent ratio of 8:1, and subsequently of 3:1, and was
impacted marginally only when the COD: SO(2-) 4 ratio was 1:2. Specific
methanogenic activity assays indicated a complex set of interactions between
sulfate-reducing bacteria (SRB), methanogens and homoacetogenic bacteria. SO(2-)
4 addition resulted in predominantly acetoclastic, rather than hydrogenotrophic,
methanogenesis until >600 days of SO(2-) 4-influenced bioreactor operation.
Temporal microbial community development was monitored by denaturation gradient
gel electrophoresis (DGGE) of 16S rRNA genes. Fluorescence in situ hybridizations
(FISH), qPCR and microsensor analysis were combined to investigate the
distribution of microbial groups, and particularly SRB and methanogens, along the
structure of granular biofilms. qPCR data indicated that sulfidogenic genes were
present in methanogenic and sulfidogenic biofilms, indicating the potential for
sulfate reduction even in bioreactors not exposed to SO(2-) 4. Although the
architecture of methanogenic and sulfidogenic granules was similar, indicating
the presence of SRB even in methanogenic systems, FISH with rRNA targets found
that the SRB were more abundant in the sulfidogenic biofilms. Methanosaeta
species were the predominant, keystone members of the archaeal community, with
the complete absence of the Methanosarcina species in the experimental bioreactor
by trial conclusion. Microsensor data suggested the ordered distribution of
sulfate reduction and sulfide accumulation, even in methanogenic granules.
PMID- 25120536
TI - Production of a recombinant vaccine candidate against Burkholderia pseudomallei
exploiting the bacterial N-glycosylation machinery.
AB - Vaccines developing immune responses toward surface carbohydrates conjugated to
proteins are effective in preventing infection and death by bacterial pathogens.
Traditional production of these vaccines utilizes complex synthetic chemistry to
acquire and conjugate the glycan to a protein. However, glycoproteins produced by
bacterial protein glycosylation systems are significantly easier to produce, and
could possible be used as vaccine candidates. In this work, we functionally
expressed the Burkholderia pseudomallei O polysaccharide (OPS II), the
Campylobacter jejuni oligosaccharyltransferase (OTase), and a suitable
glycoprotein (AcrA) in a designer E. coli strain with a higher efficiency for
production of glycoconjugates. We were able to produce and purify the OPS II-AcrA
glycoconjugate, and MS analysis confirmed correct glycan was produced and
attached. We observed the attachment of the O-acetylated deoxyhexose directly to
the acceptor protein, which expands the range of substrates utilized by the OTase
PglB. Injection of the glycoprotein into mice generated an IgG immune response
against B. pseudomallei, and this response was partially protective against an
intranasal challenge. Our experiments show that bacterial engineered
glycoconjugates can be utilized as vaccine candidates against B. pseudomallei.
Additionally, our new E. coli strain SDB1 is more efficient in glycoprotein
production, and could have additional applications in the future.
PMID- 25120537
TI - Identification of a cyclic-di-GMP-modulating response regulator that impacts
biofilm formation in a model sulfate reducing bacterium.
AB - We surveyed the eight putative cyclic-di-GMP-modulating response regulators (RRs)
in Desulfovibrio vulgaris Hildenborough that are predicted to function via two
component signaling. Using purified proteins, we examined cyclic-di-GMP (c-di
GMP) production or turnover in vitro of all eight proteins. The two RRs
containing only GGDEF domains (DVU2067, DVU0636) demonstrated c-di-GMP production
activity in vitro. Of the remaining proteins, three RRs with HD-GYP domains
(DVU0722, DVUA0086, and DVU2933) were confirmed to be Mn(2+)-dependent
phosphodiesterases (PDEs) in vitro and converted c-di-GMP to its linear form,
pGpG. DVU0408, containing both c-di-GMP production (GGDEF) and degradation
domains (EAL), showed c-di-GMP turnover activity in vitro also with production of
pGpG. No c-di-GMP related activity could be assigned to the RR DVU0330,
containing a metal-dependent phosphohydrolase HD-OD domain, or to the HD-GYP
domain RR, DVU1181. Studies included examining the impact of overexpressed cyclic
di-GMP-modulating RRs in the heterologous host E. coli and led to the
identification of one RR, DVU0636, with increased cellulose production.
Evaluation of a transposon mutant in DVU0636 indicated that the strain was
impaired in biofilm formation and demonstrated an altered carbohydrate:protein
ratio relative to the D. vulgaris wild type biofilms. However, grown in liquid
lactate/sulfate medium, the DVU0636 transposon mutant showed no growth impairment
relative to the wild-type strain. Among the eight candidates, only the transposon
disruption mutant in the DVU2067 RR presented a growth defect in liquid culture.
Our results indicate that, of the two diguanylate cyclases (DGCs) that function
as part of two-component signaling, DVU0636 plays an important role in biofilm
formation while the function of DVU2067 has pertinence in planktonic growth.
PMID- 25120535
TI - Deciphering the role of DC subsets in MCMV infection to better understand immune
protection against viral infections.
AB - Infection of mice with murine cytomegalovirus (MCMV) recapitulates many
physiopathological characteristics of human CMV infection and enables studying
the interactions between a virus and its natural host. Dendritic cells (DC) are
mononuclear phagocytes linking innate and adaptive immunity which are both
necessary for MCMV control. DC are critical for the induction of cellular
immunity because they are uniquely efficient for the activation of naive T cells
during their first encounter with a pathogen. DC are equipped with a variety of
innate immune recognition receptors (I2R2) allowing them to detect pathogens or
infections and to engulf molecules, microorganisms or cellular debris. The
combinatorial engagement of I2R2 during infections controls DC maturation and
shapes their response in terms of cytokine production, activation of natural
killer (NK) cells and functional polarization of T cells. Several DC subsets
exist which express different arrays of I2R2 and are specialized in distinct
functions. The study of MCMV infection helped deciphering the physiological roles
of DC subsets and their molecular regulation. It allowed the identification and
first in vivo studies of mouse plasmacytoid DC which produce high level of
interferons-alpha/beta early after infection. Despite its ability to infect DC
and dampen their functions, MCMV induces very robust, efficient and long-lasting
CD8 T cell responses. Their priming may rely on the unique ability of uninfected
XCR1(+) DC to cross-present engulfed viral antigens and thus to counter MCMV
interference with antigen presentation. A balance appears to have been reached
during co-evolution, allowing controlled replication of the virus for horizontal
spread without pathological consequences for the immunocompetent host. We will
discuss the role of the interplay between the virus and DC in setting this
balance, and how advancing this knowledge further could help develop better
vaccines against other intracellular infectious agents.
PMID- 25120538
TI - HTLV-1 and HTLV-2: highly similar viruses with distinct oncogenic properties.
AB - HTLV-1 and HTLV-2 share broad similarities in their overall genetic organization
and expression pattern, but they differ substantially in their pathogenic
properties. This review outlines distinctive features of HTLV-1 and HTLV-2 that
might provide clues to explain their distinct clinical outcomes. Differences in
the kinetics of viral mRNA expression, functional properties of the regulatory
and accessory proteins, and interactions with cellular factors and signal
transduction pathways are discussed.
PMID- 25120542
TI - Articles from the 15th ICI Meeting in Milan, Italy.
PMID- 25120540
TI - Ontogenic, Phenotypic, and Functional Characterization of XCR1(+) Dendritic Cells
Leads to a Consistent Classification of Intestinal Dendritic Cells Based on the
Expression of XCR1 and SIRPalpha.
AB - In the past, lack of lineage markers confounded the classification of dendritic
cells (DC) in the intestine and impeded a full understanding of their location
and function. We have recently shown that the chemokine receptor XCR1 is a
lineage marker for cross-presenting DC in the spleen. Now, we provide evidence
that intestinal XCR1(+) DC largely, but not fully, overlap with CD103(+) CD11b(-)
DC, the hypothesized correlate of "cross-presenting DC" in the intestine, and are
selectively dependent in their development on the transcription factor Batf3.
XCR1(+) DC are located in the villi of the lamina propria of the small intestine,
the T cell zones of Peyer's patches, and in the T cell zones and sinuses of the
draining mesenteric lymph node. Functionally, we could demonstrate for the first
time that XCR1(+)/CD103(+) CD11b(-) DC excel in the cross-presentation of orally
applied antigen. Together, our data show that XCR1 is a lineage marker for cross
presenting DC also in the intestinal immune system. Further, extensive phenotypic
analyses reveal that expression of the integrin SIRPalpha consistently demarcates
the XCR1(-) DC population. We propose a simplified and consistent classification
system for intestinal DC based on the expression of XCR1 and SIRPalpha.
PMID- 25120541
TI - Toll-like receptor-4 modulation for cancer immunotherapy.
PMID- 25120539
TI - Blowing on embers: commensal microbiota and our immune system.
AB - Vertebrates have co-evolved with microorganisms resulting in a symbiotic
relationship, which plays an important role in health and disease. Skin and
mucosal surfaces are colonized with a diverse population of commensal microbiota,
over 1000 species, outnumbering the host cells by 10-fold. In the past 40 years,
studies have built on the idea that commensal microbiota is in constant contact
with the host immune system and thus influence immune function. Recent studies,
focusing on mutualism in the gut, have shown that commensal microbiota seems to
play a critical role in the development and homeostasis of the host immune
system. In particular, the gut microbiota appears to direct the organization and
maturation of lymphoid tissues and acts both locally and systemically to regulate
the recruitment, differentiation, and function of innate and adaptive immune
cells. While the pace of research in the area of the mucosal-immune interface has
certainly intensified over the last 10 years, we are still in the early days of
this field. Illuminating the mechanisms of how gut microbes shape host immunity
will enhance our understanding of the causes of immune-mediated pathologies and
improve the design of next-generation vaccines. This review discusses the recent
advances in this field, focusing on the close relationship between the adaptive
immune system and commensal microbiota, a constant and abundant source of foreign
antigens.
PMID- 25120543
TI - SOCS Proteins in Macrophage Polarization and Function.
PMID- 25120544
TI - The Intercellular Metabolic Interplay between Tumor and Immune Cells.
AB - Functional and effective immune response requires a metabolic rewiring of immune
cells to meet their energetic and anabolic demands. Beyond this, the availability
of extracellular and intracellular metabolites may serve as metabolic signals
interconnecting with cellular signaling events to influence cellular fate and
immunological function. As such, tumor microenvironment represents a dramatic
example of metabolic derangement, where the highly metabolic demanding tumor
cells may compromise the function of some immune cells by competing nutrients (a
form of intercellular competition), meanwhile may support the function of other
immune cells by forming a metabolic symbiosis (a form of intercellular
collaboration). It has been well known that tumor cells harness immune system
through information exchanges that are largely attributed to soluble protein
factors and intercellular junctions. In this review, we will discuss recent
advance on tumor metabolism and immune metabolism, as well as provide examples of
metabolic communications between tumor cells and immune system, which may
represent a novel mechanism of conveying tumor-immune privilege.
PMID- 25120545
TI - Strategies for designing and monitoring malaria vaccines targeting diverse
antigens.
AB - After more than 50 years of intensive research and development, only one malaria
vaccine candidate, "RTS,S," has progressed to Phase 3 clinical trials. Despite
only partial efficacy, this candidate is now forecast to become the first
licensed malaria vaccine. Hence, more efficacious second-generation malaria
vaccines that can significantly reduce transmission are urgently needed. This
review will focus on a major obstacle hindering development of effective malaria
vaccines: parasite antigenic diversity. Despite extensive genetic diversity in
leading candidate antigens, vaccines have been and continue to be formulated
using recombinant antigens representing only one or two strains. These vaccine
strains represent only a small fraction of the diversity circulating in natural
parasite populations, leading to escape of non-vaccine strains and challenging
investigators' abilities to measure strain-specific efficacy in vaccine trials.
Novel strategies are needed to overcome antigenic diversity in order for vaccine
development to succeed. Many studies have now cataloged the global diversity of
leading Plasmodium falciparum and Plasmodium vivax vaccine antigens. In this
review, we describe how population genetic approaches can be applied to this rich
data source to predict the alleles that best represent antigenic diversity,
polymorphisms that contribute to it, and to identify key polymorphisms associated
with antigenic escape. We also suggest an approach to summarize the known global
diversity of a given antigen to predict antigenic diversity, how to select
variants that best represent the strains circulating in natural parasite
populations and how to investigate the strain-specific efficacy of vaccine
trials. Use of these strategies in the design and monitoring of vaccine trials
will not only shed light on the contribution of genetic diversity to the
antigenic diversity of malaria, but will also maximize the potential of future
malaria vaccine candidates.
PMID- 25120547
TI - Visualizing T Cell Migration in situ.
AB - Mounting a protective immune response is critically dependent on the orchestrated
movement of cells within lymphoid tissues. The structure of secondary lymphoid
organs regulates immune responses by promoting optimal cell-cell and cell
extracellular matrix interactions. Naive T cells are initially activated by
antigen presenting cells in secondary lymphoid organs. Following priming,
effector T cells migrate to the site of infection to exert their functions.
Majority of the effector cells die while a small population of antigen-specific T
cells persists as memory cells in distinct anatomical locations. The persistence
and location of memory cells in lymphoid and non-lymphoid tissues is critical to
protect the host from re-infection. The localization of memory T cells is
carefully regulated by several factors including the highly organized secondary
lymphoid structure, the cellular expression of chemokine receptors and
compartmentalized secretion of their cognate ligands. This balance between the
anatomy and the ordered expression of cell surface and soluble proteins regulates
the subtle choreography of T cell migration. In recent years, our understanding
of cellular dynamics of T cells has been advanced by the development of new
imaging techniques allowing in situ visualization of T cell responses. Here, we
review the past and more recent studies that have utilized sophisticated imaging
technologies to investigate the migration dynamics of naive, effector, and memory
T cells.
PMID- 25120546
TI - Cancer stem cell immunology: key to understanding tumorigenesis and tumor immune
escape?
AB - Cancer stem cell (CSC) biology and tumor immunology have shaped our understanding
of tumorigenesis. However, we still do not fully understand why tumors can be
contained but not eliminated by the immune system and whether rare CSCs are
required for tumor propagation. Long latency or recurrence periods have been
described for most tumors. Conceptually, this requires a subset of malignant
cells which is capable of initiating tumors, but is neither eliminated by immune
cells nor able to grow straight into overt tumors. These criteria would be
fulfilled by CSCs. Stem cells are pluripotent, immune-privileged, and long
living, but depend on specialized niches. Thus, latent tumors may be maintained
by a niche-constrained reservoir of long-living CSCs that are exempt from
immunosurveillance while niche-independent and more immunogenic daughter cells
are constantly eliminated. The small subpopulation of CSCs is often held
responsible for tumor initiation, metastasis, and recurrence. Experimentally,
this hypothesis was supported by the observation that only this subset can
propagate tumors in non-obese diabetic/scid mice, which lack T and B cells. Yet,
the concept was challenged when an unexpectedly large proportion of melanoma
cells were found to be capable of seeding complex tumors in mice which further
lack NK cells. Moreover, the link between stem cell-like properties and
tumorigenicity was not sustained in these highly immunodeficient animals. In
humans, however, tumor-propagating cells must also escape from immune-mediated
destruction. The ability to persist and to initiate neoplastic growth in the
presence of immunosurveillance - which would be lost in a maximally
immunodeficient animal model - could hence be a decisive criterion for CSCs.
Consequently, integrating scientific insight from stem cell biology and tumor
immunology to build a new concept of "CSC immunology" may help to reconcile the
outlined contradictions and to improve our understanding of tumorigenesis.
PMID- 25120548
TI - Loss of Arabidopsis GAUT12/IRX8 causes anther indehiscence and leads to reduced G
lignin associated with altered matrix polysaccharide deposition.
AB - GAlactUronosylTransferase12 (GAUT12)/IRregular Xylem8 (IRX8) is a putative
glycosyltransferase involved in Arabidopsis secondary cell wall biosynthesis.
Previous work showed that Arabidopsis irregular xylem8 (irx8) mutants have
collapsed xylem due to a reduction in xylan and a lesser reduction in a
subfraction of homogalacturonan (HG). We now show that male sterility in the irx8
mutant is due to indehiscent anthers caused by reduced deposition of xylan and
lignin in the endothecium cell layer. The reduced lignin content was demonstrated
by histochemical lignin staining and pyrolysis Molecular Beam Mass Spectrometry
(pyMBMS) and is associated with reduced lignin biosynthesis in irx8 stems.
Examination of sequential chemical extracts of stem walls using 2D (13)C-(1)H
Heteronuclear Single-Quantum Correlation (HSQC) NMR spectroscopy and antibody
based glycome profiling revealed a reduction in G lignin in the 1 M KOH extract
and a concomitant loss of xylan, arabinogalactan and pectin epitopes in the
ammonium oxalate, sodium carbonate, and 1 M KOH extracts from the irx8 walls
compared with wild-type walls. Immunolabeling of stem sections using the
monoclonal antibody CCRC-M138 reactive against an unsubstituted xylopentaose
epitope revealed a bi-lamellate pattern in wild-type fiber cells and a collapsed
bi-layer in irx8 cells, suggesting that at least in fiber cells, GAUT12
participates in the synthesis of a specific layer or type of xylan or helps to
provide an architecture framework required for the native xylan deposition
pattern. The results support the hypothesis that GAUT12 functions in the
synthesis of a structure required for xylan and lignin deposition during
secondary cell wall formation.
PMID- 25120549
TI - Structural divergence of plant TCTPs.
AB - The Translationally Controlled Tumor Protein (TCTP) is a highly conserved protein
at the level of sequence, considered to play an essential role in the regulation
of growth and development in eukaryotes. However, this function has been inferred
from studies in a few model systems, such as mice and mammalian cell lines,
Drosophila and Arabidopsis. Thus, the knowledge regarding this protein is far
from complete. In the present study bioinformatic analysis showed the presence of
one or more TCTP genes per genome in plants with highly conserved signatures and
subtle variations at the level of primary structure but with more noticeable
differences at the level of predicted three-dimensional structures. These
structures show differences in the "pocket" region close to the center of the
protein and in its flexible loop domain. In fact, all predictive TCTP structures
can be divided into two groups: (1) AtTCTP1-like and (2) CmTCTP-like, based on
the predicted structures of an Arabidopsis TCTP and a Cucurbita maxima TCTP;
according to this classification we propose that their probable function in
plants may be inferred in principle. Thus, different TCTP genes in a single
organism may have different functions; additionally, in those species harboring a
single TCTP gene this could carry multiple functions. On the other hand, in
silico analysis of AtTCTP1-like and CmTCTP-like promoters suggest that these
share common motifs but with different abundance, which may underscore
differences in their gene expression patterns. Finally, the absence of TCTP genes
in most chlorophytes with the exception of Coccomyxa subellipsoidea, indicates
that other proteins perform the roles played by TCTP or the pathways regulated by
TCTP occur through alternative routes. These findings provide insight into the
evolution of this gene family in plants.
PMID- 25120551
TI - Programmed cell death (PCD): an essential process of cereal seed development and
germination.
AB - The life cycle of cereal seeds can be divided into two phases, development and
germination, separated by a quiescent period. Seed development and germination
require the growth and differentiation of new tissues, but also the ordered
disappearance of cells, which takes place by a process of programmed cell death
(PCD). For this reason, cereal seeds have become excellent model systems for the
study of developmental PCD in plants. At early stages of seed development,
maternal tissues such as the nucellus, the pericarp, and the nucellar projections
undergo a progressive degeneration by PCD, which allows the remobilization of
their cellular contents for nourishing new filial tissues such as the embryo and
the endosperm. At a later stage, during seed maturation, the endosperm undergoes
PCD, but these cells remain intact in the mature grain and their contents will
not be remobilized until germination. Thus, the only tissues that remain alive
when seed development is completed are the embryo axis, the scutellum and the
aleurone layer. In germinating seeds, both the scutellum and the aleurone layer
play essential roles in producing the hydrolytic enzymes for the mobilization of
the storage compounds of the starchy endosperm, which serve to support early
seedling growth. Once this function is completed, scutellum and aleurone cells
undergo PCD; their contents being used to support the growth of the germinated
embryo. PCD occurs with tightly controlled spatial-temporal patterns allowing
coordinated fluxes of nutrients between the different seed tissues. In this
review, we will summarize the current knowledge of the tissues undergoing PCD in
developing and germinating cereal seeds, focussing on the biochemical features of
the process. The effect of hormones and redox regulation on PCD control will be
discussed.
PMID- 25120550
TI - Mathematical modeling reveals that metabolic feedback regulation of SnRK1 and
hexokinase is sufficient to control sugar homeostasis from energy depletion to
full recovery.
AB - Sucrose and trehalose-6-phosphate (T6P) are central compounds in the regulation
and orchestration of whole plant metabolism, growth, development, and flowering.
To evaluate their highly complex and regulatory interaction with the two
conserved sugar and energy sensors Snf1-related protein kinase 1 (SnRK1), an AMPK
related protein kinase, and hexokinase (Hxk), we developed a kinetic model which
demonstrates the subtle metabolic control of sugar homeostasis in a wide range of
concentrations without the need for changes in gene expression or protein
concentrations. Our model approach is based on a comprehensive set of published
metabolite concentrations under various conditions and coupled enzyme kinetics
accounting for the role of SnRK1 and Hxk in the sugar and energy homeostasis.
This allowed us to investigate interactions between sugar phosphates, such as
T6P, which are metabolic inhibitors of SnRK1 and Hxk, and sucrose synthesis
during the transition from carbon deficiency to availability. Model simulations
and sensitivity analyses indicated that slight changes in SnRK1 activity induced
by allosteric effectors may be sufficient to explain a dramatic readjustment of
metabolic homeostasis. This may comprise up to 10-fold changes in metabolite
concentrations. Further, the Hxk/T6P/SnRK1 interaction implemented in the model
supports the interpretation of phenotypic and transcriptomic changes observed in
Hxk overexpressing plants. Finally, our approach presents a theoretical framework
to kinetically link metabolic networks to underlying regulatory instances.
PMID- 25120552
TI - Regulation of cell fate determination in plants.
PMID- 25120554
TI - Zn(2+)-dependent surface behavior of diacylglycerol pyrophosphate and its
mixtures with phosphatidic acid at different pHs.
AB - Diacylglycerol pyrophosphate (DGPP) is a minor lipid that attenuates the
phosphatidic acid (PA) signal, and also DGPP itself would be a signaling lipid.
Diacylglycerol pyrophosphate is an anionic phospholipid with a pyrophosphate
group attached to diacylglycerol that was shown to respond to changes of pH, thus
affecting the surface organization of DGPP and their interaction with PA. In this
work, we have investigated how the presence of Zn(2+) modulates the surface
organization of DGPP and its interaction with PA at acidic and basic pHs. Both
lipids formed expanded monolayers at pHs 5 and 8. At pH 5, monolayers formed by
DGPP became stiffer when Zn(2+)was added to the subphase, while the surface
potential decreased. At this pH, Zn(2+) induced a phase transition from an
expanded to a condensed-phase state in monolayers formed by PA. Conversely, at pH
8 the effects induced by the presence of Zn(2+) on the surface behaviors of the
pure lipids were smaller. Thus, the interaction of the bivalent cation with both
lipids was modulated by pH and by the ionization state of the polar head groups.
Mixed monolayers of PA and DGPP showed a non-ideal behavior and were not affected
by the presence of Zn(2+) at pH 8. This could be explained considering that when
mixed, the lipids formed a closely packed monolayer that could not be further
modified by the cation. Our results indicate that DGPP and PA exhibit expanded-
and condensed-phase states depending on pH, on the proportion of each lipid in
the film and on the presence of Zn(2+). This may have implications for a possible
role of DGPP as a signaling lipid molecule.
PMID- 25120556
TI - Quality assessment and control of high-throughput sequencing data.
PMID- 25120555
TI - Primary analysis of repeat elements of the Asian seabass (Lates calcarifer)
transcriptome and genome.
AB - As part of our Asian seabass genome project, we are generating an inventory of
repeat elements in the genome and transcriptome. The karyotype showed a diploid
number of 2n = 24 chromosomes with a variable number of B-chromosomes. The
transcriptome and genome of Asian seabass were searched for repetitive elements
with experimental and bioinformatics tools. Six different types of repeats
constituting 8-14% of the genome were characterized. Repetitive elements were
clustered in the pericentromeric heterochromatin of all chromosomes, but some of
them were preferentially accumulated in pretelomeric and pericentromeric regions
of several chromosomes pairs and have chromosomes specific arrangement. From the
dispersed class of fish-specific non-LTR retrotransposon elements Rex1 and MAUI
like repeats were analyzed. They were wide-spread both in the genome and
transcriptome, accumulated on the pericentromeric and peritelomeric areas of all
chromosomes. Every analyzed repeat was represented in the Asian seabass
transcriptome, some showed differential expression between the gonads. The other
group of repeats analyzed belongs to the rRNA multigene family. FISH signal for
5S rDNA was located on a single pair of chromosomes, whereas that for 18S rDNA
was found on two pairs. A BAC-derived contig containing rDNA was sequenced and
assembled into a scaffold containing incomplete fragments of 18S rDNA. Their
assembly and chromosomal position revealed that this part of Asian seabass genome
is extremely rich in repeats containing evolutionarily conserved and novel
sequences. In summary, transcriptome assemblies and cDNA data are suitable for
the identification of repetitive DNA from unknown genomes and for comparative
investigation of conserved elements between teleosts and other vertebrates.
PMID- 25120553
TI - Looking at plant cell cycle from the chromatin window.
AB - The cell cycle is defined by a series of complex events, finely coordinated
through hormonal, developmental and environmental signals, which occur in a
unidirectional manner and end up in producing two daughter cells. Accumulating
evidence reveals that chromatin is not a static entity throughout the cell cycle.
In fact, there are many changes that include nucleosome remodeling, histone
modifications, deposition and exchange, among others. Interestingly, it is
possible to correlate the occurrence of several of these chromatin-related events
with specific processes necessary for cell cycle progression, e.g., licensing of
DNA replication origins, the E2F-dependent transcriptional wave in G1, the
activation of replication origins in S-phase, the G2-specific transcription of
genes required for mitosis or the chromatin packaging occurring in mitosis.
Therefore, an emerging view is that chromatin dynamics must be considered as an
intrinsic part of cell cycle regulation. In this article, we review the main
features of several key chromatin events that occur at defined times throughout
the cell cycle and discuss whether they are actually controlling the transit
through specific cell cycle stages.
PMID- 25120557
TI - Development and in silico evaluation of large-scale metabolite identification
methods using functional group detection for metabolomics.
AB - Large-scale identification of metabolites is key to elucidating and modeling
metabolism at the systems level. Advances in metabolomics technologies,
particularly ultra-high resolution mass spectrometry (MS) enable comprehensive
and rapid analysis of metabolites. However, a significant barrier to meaningful
data interpretation is the identification of a wide range of metabolites
including unknowns and the determination of their role(s) in various metabolic
networks. Chemoselective (CS) probes to tag metabolite functional groups combined
with high mass accuracy provide additional structural constraints for metabolite
identification and quantification. We have developed a novel algorithm,
Chemically Aware Substructure Search (CASS) that efficiently detects functional
groups within existing metabolite databases, allowing for combined molecular
formula and functional group (from CS tagging) queries to aid in metabolite
identification without a priori knowledge. Analysis of the isomeric compounds in
both Human Metabolome Database (HMDB) and KEGG Ligand demonstrated a high
percentage of isomeric molecular formulae (43 and 28%, respectively), indicating
the necessity for techniques such as CS-tagging. Furthermore, these two databases
have only moderate overlap in molecular formulae. Thus, it is prudent to use
multiple databases in metabolite assignment, since each major metabolite database
represents different portions of metabolism within the biosphere. In silico
analysis of various CS-tagging strategies under different conditions for adduct
formation demonstrate that combined FT-MS derived molecular formulae and CS
tagging can uniquely identify up to 71% of KEGG and 37% of the combined KEGG/HMDB
database vs. 41 and 17%, respectively without adduct formation. This difference
between database isomer disambiguation highlights the strength of CS-tagging for
non-lipid metabolite identification. However, unique identification of complex
lipids still needs additional information.
PMID- 25120558
TI - Genome and metabolic network of "Candidatus Phaeomarinobacter ectocarpi" Ec32, a
new candidate genus of Alphaproteobacteria frequently associated with brown
algae.
AB - Rhizobiales and related orders of Alphaproteobacteria comprise several genera of
nodule-inducing symbiotic bacteria associated with plant roots. Here we describe
the genome and the metabolic network of "Candidatus Phaeomarinobacter ectocarpi"
Ec32, a member of a new candidate genus closely related to Rhizobiales and found
in association with cultures of the filamentous brown algal model Ectocarpus. The
"Ca. P. ectocarpi" genome encodes numerous metabolic pathways that may be
relevant for this bacterium to interact with algae. Notably, it possesses a large
set of glycoside hydrolases and transporters, which may serve to process and
assimilate algal metabolites. It also harbors several proteins likely to be
involved in the synthesis of algal hormones such as auxins and cytokinins, as
well as the vitamins pyridoxine, biotin, and thiamine. As of today, "Ca. P.
ectocarpi" has not been successfully cultured, and identical 16S rDNA sequences
have been found exclusively associated with Ectocarpus. However, related
sequences (>=97% identity) have also been detected free-living and in a Fucus
vesiculosus microbiome barcoding project, indicating that the candidate genus
"Phaeomarinobacter" may comprise several species, which may colonize different
niches.
PMID- 25120560
TI - The role of AGG interruptions in fragile X repeat expansions: a twenty-year
perspective.
AB - In 1994, it was suggested that AGG interruptions affect the stability of the
fragile X triplet repeat. Until recently, however, this hypothesis was not
explored on a large scale due primarily to the technical difficulty of
determining AGG interruption patterns of the two alleles in females. The recent
development of a PCR technology that overcomes this difficulty and accurately
identifies the number and position of AGGs has led to several studies that
examine their influence on repeat stability. Here, we present a historical
perspective of relevant studies published during the last 20 years on AGG
interruptions and examine those recent publications that have refined risk
estimates for repeat instability and full-mutation expansions.
PMID- 25120561
TI - HumanViCe: host ceRNA network in virus infected cells in human.
AB - Host-virus interaction via host cellular components has been an important field
of research in recent times. RNA interference mediated by short interfering RNAs
and microRNAs (miRNA), is a widespread anti-viral defense strategy. Importantly,
viruses also encode their own miRNAs. In recent times miRNAs were identified as
key players in host-virus interaction. Furthermore, viruses were shown to exploit
the host miRNA networks to suite their own need. The complex cross-talk between
host and viral miRNAs and their cellular and viral targets forms the environment
for viral pathogenesis. Apart from protein-coding mRNAs, non-coding RNAs may also
be targeted by host or viral miRNAs in virus infected cells, and viruses can
exploit the host miRNA mediated gene regulatory network via the competing
endogenous RNA effect. A recent report showed that viral U-rich non-coding RNAs
called HSUR, expressed in primate virus herpesvirus saimiri (HVS) infected T
cells, were able to bind to three host miRNAs, causing significant alteration in
cellular level for one of the miRNAs. We have predicted protein coding and non
protein-coding targets for viral and human miRNAs in virus infected cells. We
identified viral miRNA targets within host non-coding RNA loci from AGO
interacting regions in three different virus infected cells. Gene ontology (GO)
and pathway enrichment analysis of the genes comprising the ceRNA networks in the
virus infected cells revealed enrichment of key cellular signaling pathways
related to cell fate decisions and gene transcription, like Notch and Wnt
signaling pathways, as well as pathways related to viral entry, replication and
virulence. We identified a vast number of non-coding transcripts playing as
potential ceRNAs to the immune response associated genes; e.g., APOBEC family
genes, in some virus infected cells. All these information are compiled in
HumanViCe (http://gyanxet-beta.com/humanvice), a comprehensive database that
provides the potential ceRNA networks in virus infected human cells.
PMID- 25120559
TI - Endoplasmic reticulum stress in hepatic steatosis and inflammatory bowel
diseases.
AB - As an adaptive response to the overloading with misfolded proteins in the
endoplasmic reticulum (ER), ER stress plays critical roles in maintaining protein
homeostasis in the secretory pathway to avoid damage to the host. Such a
conserved mechanism is accomplished through three well-orchestrated pathways
known collectively as unfolded protein response (UPR). Persistent and
pathological ER stress has been implicated in a variety of diseases in metabolic,
inflammatory, and malignant conditions. Furthermore, ER stress is directly linked
with inflammation through UPR pathways, which modulate transcriptional programs
to induce the expression of inflammatory genes. Importantly, the inflammation
induced by ER stress is directly responsible for the pathogenesis of metabolic
and inflammatory diseases. In this review, we will discuss the potential
signaling pathways connecting ER stress with inflammation. We will also depict
the interplay between ER stress and inflammation in the pathogenesis of hepatic
steatosis, inflammatory bowel diseases and colitis-associated colon cancer.
PMID- 25120563
TI - Accelerometer-Based Method for Extracting Respiratory and Cardiac Gating
Information for Dual Gating during Nuclear Medicine Imaging.
AB - Both respiratory and cardiac motions reduce the quality and consistency of
medical imaging specifically in nuclear medicine imaging. Motion artifacts can be
eliminated by gating the image acquisition based on the respiratory phase and
cardiac contractions throughout the medical imaging procedure.
Electrocardiography (ECG), 3-axis accelerometer, and respiration belt data were
processed and analyzed from ten healthy volunteers. Seismocardiography (SCG) is a
noninvasive accelerometer-based method that measures accelerations caused by
respiration and myocardial movements. This study was conducted to investigate the
feasibility of the accelerometer-based method in dual gating technique. The SCG
provides accelerometer-derived respiratory (ADR) data and accurate information
about quiescent phases within the cardiac cycle. The correct information about
the status of ventricles and atria helps us to create an improved estimate for
quiescent phases within a cardiac cycle. The correlation of ADR signals with the
reference respiration belt was investigated using Pearson correlation. High
linear correlation was observed between accelerometer-based measurement and
reference measurement methods (ECG and Respiration belt). Above all, due to the
simplicity of the proposed method, the technique has high potential to be applied
in dual gating in clinical cardiac positron emission tomography (PET) to obtain
motion-free images in the future.
PMID- 25120562
TI - A revised dated phylogeny of the arachnid order Opiliones.
AB - Dating the Opiliones tree of life has become an important enterprise for this
group of arthropods, due to their ancient origins and important biogeographic
implications. To incorporate both methodological innovations in molecular dating
as well as new systematic discoveries of harvestman diversity, we conducted total
evidence dating on a data set uniting morphological and/or molecular sequence
data for 47 Opiliones species, including all four well-known Palaeozoic fossils,
to test the placement of both fossils and newly discovered lineages in a single
analysis. Furthermore, we investigated node dating with a phylogenomic data set
of 24,202 amino acid sites for 14 species of Opiliones, sampling all extant
suborders. In this way, we approached molecular dating of basal harvestman
phylogeny using different data sets and approaches to assess congruence of
divergence time estimates. In spite of the markedly different composition of data
sets, our results show congruence across all analyses for age estimates of basal
nodes that are well constrained with respect to fossil calibrations (e.g.,
Opiliones, Palpatores). By contrast, derived nodes that lack fossil calibrations
(e.g., the suborders Cyphophthalmi, and Laniatores) have large uncertainty
intervals in diversification times, particularly in the total evidence dating
analysis, reflecting the dearth of calibration points and undersampling of
derived lineages. Total evidence dating consistently produced older median ages
than node dating for ingroup nodes, due to the nested placement of multiple
Palaeozoic fossils. Our analyses support basal diversification of Opiliones in
the Ordovician-Devonian period, corroborating the inferred ancient origins of
this arthropod order, and underscore the importance of diversity discovery-both
paleontological and neontological-in evolutionary inference.
PMID- 25120564
TI - 15-Deoxy- gamma 12,14-prostaglandin J2 Reduces Liver Impairment in a Model of
ConA-Induced Acute Hepatic Inflammation by Activation of PPAR gamma and Reduction
in NF- kappa B Activity.
AB - Objective. 15-Deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) reduces inflammation
and has been identified as an anti-inflammatory prostaglandin in numerous animal
models. In this study, we investigated both effects of 15d-PGJ2 and its
protection mechanism in concanavalin A- (ConA-) induced autoimmune hepatitis in
mice. Materials and Methods. In vivo, Balb/C mice were injected with ConA (25
mg/kg) to induce acute autoimmune hepatitis, and 15d-PGJ2 (10 MUg or 25 MUg) was
administered 1 h before the ConA injection. The histological grade,
proinflammatory cytokine levels, and NF-kappaB and PPARgamma activity were
determined 6, 12, and 24 h after the ConA injection. In vitro, LO2 cells and
RAW264.7 cells were pretreated with 15d-PGJ2 (2 MUM) 1 h before the stimulation
with ConA (30 MUg/mL). The NF-kappaB and PPARgamma activity were determined 30
min after the ConA administration. Results. Pretreatment with 15d-PGJ2 reduced
the pathological effects of ConA-induced autoimmune hepatitis and significantly
reduced the levels of cytokines after injection. 15d-PGJ2 activated PPARgamma,
blocked the degradation of IkappaBalpha, and inhibited the translocation of NF
kappaB into the nucleus. Conclusion. These results indicate that 15d-PGJ2
protects against ConA-induced autoimmune hepatitis by reducing proinflammatory
cytokines. This reduction in inflammation may correlate with the activation of
PPARgamma and the reduction in NF-kappaB activity.
PMID- 25120565
TI - Pathogenesis of chronic urticaria: an overview.
AB - The pathogenesis of chronic urticaria is not well delineated and the treatment is
palliative as it is not tied to the pathomechanism. The centrality of mast cells
and their inappropriate activation and degranulation as the key
pathophysiological event are well established. The triggering stimuli and the
complexity of effector mechanisms remain speculative. Autoimmune origin of
chronic urticaria, albeit controversial, is well documented. Numerical and
behavioral alterations in basophils accompanied by changes in signaling molecule
expression and function as well as aberrant activation of extrinsic pathway of
coagulation are other alternative hypotheses. It is also probable that mast cells
are involved in the pathogenesis through mechanisms that extend beyond high
affinity IgE receptor stimulation. An increasing recognition of chronic urticaria
as an immune mediated inflammatory disorder related to altered cytokine-chemokine
network consequent to immune dysregulation resulting from disturbed innate
immunity is emerging as yet another pathogenic explanation. It is likely that
these different pathomechanisms are interlinked rather than independent cascades,
acting either synergistically or sequentially to produce clinical expression of
chronic urticaria. Insights into the complexities of pathogenesis may provide an
impetus to develop safer, efficacious, and targeted immunomodulators and
biological treatment for severe, refractory chronic urticaria.
PMID- 25120567
TI - Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS
and eNOS.
AB - Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious
Gram-negative infections. However, its usefulness is limited by its
nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was
reported to prevent or decrease tissue injury. The aim of this study is to
evaluate the potential protective effects of sildenafil on gentamicin-induced
nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100
mg/kg/day, i.p.) for 6 days with and without sildenafil. Sildenafil
administration resulted in nephroprotective effect in gentamicin-intoxicated rats
as it significantly decreased serum creatinine and urea, urinary albumin, and
renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in
renal catalase and superoxide dismutase activities compared to gentamicin-treated
rats. Moreover, immunohistochemical examination revealed that sildenafil
treatment markedly reduced inducible nitric oxide synthase (iNOS) expression,
while expression of endothelial nitric oxide synthase (eNOS) was markedly
enhanced. The protective effects of sildenafil were verified histopathologically.
In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity
possibly, in part, through its antioxidant activity, inhibition of iNOS
expression, and induction of eNOS production.
PMID- 25120566
TI - Zinc therapy in dermatology: a review.
AB - Zinc, both in elemental or in its salt forms, has been used as a therapeutic
modality for centuries. Topical preparations like zinc oxide, calamine, or zinc
pyrithione have been in use as photoprotecting, soothing agents or as active
ingredient of antidandruff shampoos. Its use has expanded manifold over the years
for a number of dermatological conditions including infections (leishmaniasis,
warts), inflammatory dermatoses (acne vulgaris, rosacea), pigmentary disorders
(melasma), and neoplasias (basal cell carcinoma). Although the role of oral zinc
is well-established in human zinc deficiency syndromes including acrodermatitis
enteropathica, it is only in recent years that importance of zinc as a
micronutrient essential for infant growth and development has been recognized.
The paper reviews various dermatological uses of zinc.
PMID- 25120569
TI - Identification and in vitro antimicrobial susceptibility of Brucella species
isolated from human brucellosis.
AB - Brucellosis is a world-wide zoonotic disease with a major impact on the public
health. Due to the high risk of laboratory acquired infection, limited laboratory
investigations were performed on this organism, including detailed identification
and susceptibility study. Brucella melitensis is the commonest aetiological agent
for human brucellosis in this region. The in vitro susceptibility pattern against
selected antimicrobial agents was assessed using E-test. All isolates were noted
to be sensitive to all the antimicrobial agents tested except for rifampicin
where elevated MIC > 1 MUg/mL was noted in 30 out of 41 isolates tested.
PMID- 25120570
TI - Degree and rate of growth discordance in dichorionic twins conceived by in vitro
fertilization.
AB - Objective. Our objective was to estimate degree and rate of discordant growth and
its impact on perinatal outcome in dichorionic twin pregnancies conceived by in
vitro fertilization (IVF) compared to those conceived spontaneously. Study
Design. Growth discordance was defined as 90th percentiles for the study
population. Adverse perinatal outcome was defined as 5-minute Apgar score <7
and/or admission to neonatal intensive care unit. Results. In the total study
population of dichorionic twins (176 conceived by IVF and 215 spontaneously), 30%
discordant growth represented the 90th percentile. After adjusting for
gestational age, discordant twins conceived by IVF or spontaneously were at
higher risk for adverse perinatal outcome (hazard ratio 4.4; 95% CI 2.4-8.3, P <
0.0001; hazard ratio 2.5; 95% CI 1.5-4.4, P = 0.001, resp.). Similar rates of 5
minute Apgar score <7, admission to neonatal intensive care unit, and delivery
<34 weeks were found between discordant twins conceived by IVF and those
conceived spontaneously. Conclusion. Dichorionic twins conceived by IVF are at
similar risk for the rate and degree of discordant growth and adverse perinatal
outcome compared to dichorionic twins conceived spontaneously.
PMID- 25120571
TI - Stem cells: innovations in clinical applications.
AB - The use of mesenchymal stem cells (MSCs) as clinical therapeutics is a relatively
new avenue of study for treatment of a variety of diseases. The therapeutic
impact of the MSCs is based upon their multiplicities of function and interaction
with host tissues. MSCs can be anti-inflammatory, antifibrotic, antimicrobial,
and regenerative, all which may improve outcomes in scenarios of damaged tissues
and inflammation. Although most studies focus on utilizing MSCs to direct
clinical efficacy, it is the ability to orchestrate host response in surrounding
tissue that is especially unique and versatile. This orchestration of host
response can be applied to a variety of clinical scenarios not only through cell
cell interactions but also through production of bioactive secreted factors.
These bioactive factors include small proteins, chemokines, cytokines, and other
cellular regulators. These factors have the capacity to induce angiogenesis or
blood vessel development, be chemotactic, and induce cellular recruitment. MSCs
also have the capacity to differentiate with the implicated environment to
regenerate tissue or accommodate host tissue in a cell specific manner. The
differentiation cannot only be done in vivo but also can be optimized in vitro
prior to in vivo administration, potentiating the versatility of the MSCs and
opening avenues for corrective therapy and cell delivery of genes. The
differentiation process depends on the environment with which the MSCs are put
and results in active communication between the newly administered cells host
tissue. Since these properties have been identified, there are a variety of
clinical trials and studies being conducted on MSCs ability to treat human
disease. This review outlines the potential use of MSCs, the types of tissue, and
the innovative applications of MSCs for the treatment of diseases.
PMID- 25120572
TI - Clinical, Molecular, and Epidemiological Analysis of Dengue Cases during a Major
Outbreak in the Midwest Region of Minas Gerais, Brazil.
AB - This study aims to perform the first molecular and clinical-epidemiological
analysis of dengue cases in Divinopolis, MG, Brazil. Data from 4,110 cases of
dengue were accessed and 190 clinical samples were collected for molecular
analyses. In this study, 2.7% of the men and 3.0% of the women were admitted to
hospital. There was no association between gender and hospital admission. The
symptoms observed in this study are according to the Health Ministry, but fever
was present in 82.2% and not in 100% of cases. The chance of hospital admission
was 1.55 higher in patients with any kind of bleeding (334) and 2.4% of
individuals without bleeding were also hospitalized due to other warning signs.
In the molecular analyses, 23% of the samples were positive for DENV. DENV-2 and
DENV-3 were identified in 2010, DENV-3 in 2011, DENV-1 in 2012, and DENV-1 and
DENV-4 in 2013. DENV detection was possible in samples with only one day of
symptoms. This first report of dengue data in Divinopolis provided more insight
into the viral types and effects of disease in the city, confirming the need for
caution in assessing cases of suspected dengue and for revision of the criteria
proposed by the Health Ministry to classify cases of the disease.
PMID- 25120573
TI - Ginsenoside rb1 protects neonatal rat cardiomyocytes from hypoxia/ischemia
induced apoptosis and inhibits activation of the mitochondrial apoptotic pathway.
AB - Aim. To investigate the effect of Ginsenoside Rb1 (GS-Rb1) on hypoxia/ischemia
(H/I) injury in cardiomyocytes in vitro and the mitochondrial apoptotic pathway
mediated mechanism. Methods. Neonatal rat cardiomyocytes (NRCMs) for the H/I
groups were kept in DMEM without glucose and serum, and were placed into a
hypoxic jar for 24 h. GS-Rb1 at concentrations from 2.5 to 40 uM was given during
hypoxic period for 24 h. NRCMs injury was determined by MTT and lactate
dehydrogenase (LDH) leakage assay. Cell apoptosis, ROS accumulation, and
mitochondrial membrane potential (MMP) were assessed by flow cytometry. Cytosolic
translocation of mitochondrial cytochrome c and Bcl-2 family proteins were
determined by Western blot. Caspase-3 and caspase-9 activities were determined by
the assay kit. Results. GS-Rb1 significantly reduced cell death and LDH leakage
induced by H/I. It also reduced H/I induced NRCMs apoptosis induced by H/I, in
accordance with a minimal reactive oxygen species (ROS) burst. Moreover, GS-Rb1
markedly decreased the translocation of cytochrome c from the mitochondria to the
cytosol, increased the Bcl-2/ Bax ratio, and preserved mitochondrial
transmembrane potential (DeltaPsim). Its administration also inhibited activities
of caspase-9 and caspase-3. Conclusion. Administration of GS-Rb1 during H/I in
vitro is involved in cardioprotection by inhibiting apoptosis, which may be due
to inhibition of the mitochondrial apoptotic pathway.
PMID- 25120574
TI - Effect of yoga on pain, brain-derived neurotrophic factor, and serotonin in
premenopausal women with chronic low back pain.
AB - Background. Serotonin and brain-derived neurotrophic factor (BDNF) are known to
be modulators of nociception. However, pain-related connection between yoga and
those neuromodulators has not been investigated. Therefore, we aimed to evaluate
the effect of yoga on pain, BDNF, and serotonin. Methods. Premenopausal women
with chronic low back pain practiced yoga three times a week for 12 weeks. At
baseline and after 12 weeks, back pain intensity was measured using visual
analogue scale (VAS), and serum BDNF and serotonin levels were evaluated.
Additionally, back flexibility and level of depression were assessed. Results.
After 12-week yoga, VAS decreased in the yoga group (P < 0.001), whereas it
increased (P < 0.05) in the control group. Back flexibility was improved in the
yoga group (P < 0.01). Serum BDNF increased in the yoga group (P < 0.01), whereas
it tended to decrease in the control group (P = 0.05). Serum serotonin maintained
in the yoga group, while it reduced (P < 0.01) in the control group. The
depression level maintained in the yoga group, whereas it tended to increase in
the control group (P = 0.07). Conclusions. We propose that BDNF may be one of the
key factors mediating beneficial effects of yoga on chronic low back pain.
PMID- 25120576
TI - Tanshinone IIA Downregulates HMGB1 and TLR4 Expression in a Spinal Nerve Ligation
Model of Neuropathic Pain.
AB - Fifty-four Sprague-Dawley rats weighing 200~240 g were randomly divided into sham
operated group (sham group), vehicle-treated SNL group (model group), and Tan IIA
treated SNL group (Tan IIA group). Tan IIA was administered intraperitoneally to
rats in the Tan IIA-treated group at a dose of 30 mg/kg daily for 14 days after
SNL surgery. Paw withdrawal mechanical thresholds (PWTs) and paw withdrawal
thermal latencies (PWLs) were measured. High-mobility group box 1 (HMGB1) and
Toll-like Receptor 4 (TLR4) mRNA and protein expression in the spinal cord were
measured. Tumour necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL
1beta), and interleukin-10 (IL-10) in the spinal cord were measured, too. Both
the mechanical and heat pain thresholds were significantly decreased. After Tan
IIA treatment, HMGB1, and TLR4 mRNA and protein levels, the expression of TNF
alpha and IF-1beta was reduced significantly. In conclusion, Tanshinone IIA
reversed SNL-induced thermal hyperalgesia and mechanical allodynia and
downregulated HMGB1 and TLR4 levels and inhibited the HMGB1-TLR4 pathway.
Tanshinone IIA inhibited TNF-alpha and IL-1beta expression but not IF-10
expression in the spinal cords of SNL rats. These results indicate that
Tanshinone IIA inhibited SNL-induced neuropathic pain via multiple effects, and
targeting the HMGB1-TLR4 pathway could serve as the basis of new antinociceptive
agents.
PMID- 25120575
TI - Xilei san ameliorates experimental colitis in rats by selectively degrading
proinflammatory mediators and promoting mucosal repair.
AB - Xilei san (XLS), a herbal preparation widely used in China for erosive and
ulcerative diseases, has been shown to be effective in ulcerative colitis (UC).
The present experiments were conducted to assess its efficacy and determine its
mechanism of action in a rat model that resembles human UC. The model was induced
by adding 4% dextran sulfate sodium (DSS) to the rats' drinking water for 7 days.
XLS was administered daily by retention enema from day 2 to day 7; the rats were
sacrificed on day 8. The colon tissues were obtained for further experiments. A
histological damage score and the activity of tissue myeloperoxidase were used to
evaluate the severity of the colitis. The colonic cytokine levels were detected
in a suspension array, and epithelial proliferation was assessed using Ki-67
immunohistochemistry. Intrarectal administration of XLS attenuated the DSS
induced colitis, as evidenced by a reduction in both the histological damage
score and myeloperoxidase activity. It also decreased the levels of
proinflammatory cytokines, but increased the mucosal repair-related cytokines. In
addition, the epithelial Ki-67 expression was upregulated by XLS. These results
suggest that XLS attenuates DSS-induced colitis by degrading proinflammatory
mediators and promoting mucosal repair. XLS could be a potential topical
treatment for human UC.
PMID- 25120577
TI - A Study on the Effect of Neurogenesis and Regulation of GSK3beta/PP2A Expression
in Acupuncture Treatment of Neural Functional Damage Caused by Focal Ischemia in
MCAO Rats.
AB - 170 SD rats were randomly divided to five groups. Rats in model group, no
acupuncture group, and acupuncture group were subjected to MCAO surgery.
Acupuncture group received 3 consecutive acupuncture treatments at a parameter
that deep in 2 mm towards apex nasi and thrust/lifted at 3 times per second for 1
minute, while model group and no-acupuncture group were no-intervention control
groups. Serious neural functional damage and sharp decrease of cerebral blood
flow, obvious infarction volume, increased nestin mRNA expression, and
immunopositive cells population (nestin(+), BrdU(+) and nestin/BrdU(+)) were
found in MCAO rats which had not been observed in normal group and sham-operated
group. However, the damage was attenuated by rat's "self-healing" capacity 3 days
after MCAO. And the "self-healing" capacity can be strengthen by acupuncture
treatment through increasing cerebral blood flow, neurogenesis, and regulation of
gene transcription or GSK-3beta and PP2A expression. In conclusion, the present
study indicates that the underlying mechanism of acupuncture treatment on neural
functional damage caused by focal ischemia injury is a multiple interaction which
may involve improved cerebral blood supply, neurogenesis, and regulation of gene
transcription or GSK-3beta and PP2A expression in MCAO rats.
PMID- 25120579
TI - Influence of providers and nurses on completion of non-targeted HIV screening in
an urgent care setting.
AB - INTRODUCTION: Despite recommendations by the Centers for Disease Control (CDC)
that all adults be offered non-targeted HIV screening in all care settings,
screening in acute-care settings remains unacceptably low. We performed an
observational study to evaluate an HIV screening pilot in an academic-community
partnership health center urgent care clinic. METHODS: We collected visit data
via encounter forms and demographic and laboratory data from electronic medical
records. A post-pilot survey of perceptions of HIV screening was administered to
providers and nurses. Multivariable analysis was used to identify factors
associated with completion of testing. RESULTS: Visit provider and triage nurse
were highly associated with both acceptance of screening and completion of
testing, as were younger age, male gender, and race/ethnicity. 23.5% of patients
completed tests, although 36.0% requested screening; time constraints as well as
risk perceptions by both the provider and patient were cited as limiting
completion of screening. Post-pilot surveys showed mixed support for ongoing HIV
screening in this setting by providers and little support by nurses. CONCLUSIONS:
Visit provider and triage nurse were strongly associated with acceptance of
testing, which may reflect variable opinions of HIV screening in this setting by
clinical staff. Among patients accepting screening, visit provider remained
strongly associated with completion of testing. Despite longstanding
recommendations for non-targeted HIV screening, further changes to improve the
testing and results process, as well as provider education and buy-in, are needed
to improve screening rates.
PMID- 25120580
TI - Therapeutic drug monitoring of voriconazole: a case report of multiple drug
interactions in a patient with an increased CYP2C19 activity.
AB - BACKGROUND: Voriconazole is metabolized by cytochrome P450 (CYP) 2C19 and CYP
3A4. Drug-drug interactions and genetic polymorphisms modulate their activities.
CASE PRESENTATION: A 35-year old African female patient with resistant HIV and a
cerebral mass of unknown origin was treated with voriconazole for a suspicion of
disseminated Aspergillosis infection. Voriconazole trough concentrations (C0)
were within target range while the patient was under esomeprazole, a CYP2C19
inhibitor. Phenotyping showed decreased CYP2C19 activity, whereas genotyping
showed a variant allele associated with increased enzyme activity. The patient
was switched to ranitidine because of the introduction of atazanavir. CYP3A4
inhibition by atazanavir combined with uninhibited CYP2C19 activity resulted in
subtherapeutic voriconazole C0. The reintroduction of esomeprazole allowed
restoring voriconazole C0 back to target range. CONCLUSION: The integration of
drug-drug interactions and pharmacogenetics data is crucial to interpret drug
concentrations correctly, thus preventing suboptimal exposure to voriconazole.
PMID- 25120581
TI - The radiographic method for evaluation of axial vertebral rotation - presentation
of the new method.
AB - The objective of this study is to present a new radiographic method for the
assessment of vertebral rotation from an antero-posterior view of conventional X
rays which is sufficiently precise in comparison with radiographic methods
presently used in clinical practice (methods of Nash-Moe and Perdriolle). This
method is based on the properties of the geometric shape of vertebrae and their
shared dimensional proportions. It means that the relation between vertebral body
width and height doesn't change significantly within the entire thoracic and
lumbar sections of the spine. In order to verify the method, we have constructed
a special device for vertebral fixation. Subsequently, the X-ray pictures of
individual human vertebrae with predefined rotation values (ranging from 0
degrees to 45 degrees by steps of 3 degrees) were radio-graphically measured and
then compared with their actual axial rotation on the vertebral rotation device.
All arithmetic averages correlate very closely with the actual values. The
verification of axial vertebral rotation with the assistance of CT and MRI
pictures of six scoliotic patients (in supine position) and the evaluation of
axial vertebral rotation by both the new radiographic method and with the
Perdriolle method proved the satisfactory accuracy of our method. The main
advantage of the newly presented radiographic method is the uncomplicated
measurement of vertebral rotation from AP projection of conventional X-ray
pictures or from its printed copies. The gold standard of the new radiographic
method is the evaluation of axial rotation of vertebrae to 30 degrees
approximately and the shape of vertebral bodies without severe structural
deformities. The new radiographic method seems to be suitable for use in clinical
practice.
PMID- 25120578
TI - Differential glycosylation of envelope gp120 is associated with differential
recognition of HIV-1 by virus-specific antibodies and cell infection.
AB - BACKGROUND: HIV-1 entry into host cells is mediated by interactions between the
virus envelope glycoprotein (gp120/gp41) and host-cell receptors. N-glycans
represent approximately 50% of the molecular mass of gp120 and serve as potential
antigenic determinants and/or as a shield against immune recognition. We
previously reported that N-glycosylation of recombinant gp120 varied, depending
on the producer cells, and the glycosylation variability affected gp120
recognition by serum antibodies from persons infected with HIV-1 subtype B.
However, the impact of gp120 differential glycosylation on recognition by broadly
neutralizing monoclonal antibodies or by polyclonal antibodies of individuals
infected with other HIV-1 subtypes is unknown. METHODS: Recombinant multimerizing
gp120 antigens were expressed in different cells, HEK 293T, T-cell,
rhabdomyosarcoma, hepatocellular carcinoma, and Chinese hamster ovary cell lines.
Binding of broadly neutralizing monoclonal antibodies and polyclonal antibodies
from sera of subtype A/C HIV-1-infected subjects with individual gp120 glycoforms
was assessed by ELISA. In addition, immunodetection was performed using Western
and dot blot assays. Recombinant gp120 glycoforms were tested for inhibition of
infection of reporter cells by SF162 and YU.2 Env-pseudotyped R5 viruses.
RESULTS: We demonstrated, using ELISA, that gp120 glycans sterically adjacent to
the V3 loop only moderately contribute to differential recognition of a short
apex motif GPGRA and GPGR by monoclonal antibodies F425 B4e8 and 447-52D,
respectively. The binding of antibodies recognizing longer peptide motifs
overlapping with GPGR epitope (268 D4, 257 D4, 19b) was significantly altered.
Recognition of gp120 glycoforms by monoclonal antibodies specific for other than
V3-loop epitopes was significantly affected by cell types used for gp120
expression. These epitopes included CD4-binding site (VRC03, VRC01, b12),
discontinuous epitope involving V1/V2 loop with the associated glycans (PG9,
PG16), and an epitope including V3-base-, N332 oligomannose-, and surrounding
glycans-containing epitope (PGT 121). Moreover, the different gp120 glycoforms
variably inhibited HIV-1 infection of reporter cells. CONCLUSION: Our data
support the hypothesis that the glycosylation machinery of different cells shapes
gp120 glycosylation and, consequently, impacts envelope recognition by specific
antibodies as well as the interaction of HIV-1 gp120 with cellular receptors.
These findings underscore the importance of selection of appropriately
glycosylated HIV-1 envelope as a vaccine antigen.
PMID- 25120582
TI - Human Mammary Tumor Virus (HMTV) sequences in human milk.
AB - BACKGROUND: Retroviral sequences 90-95% homologous to the mouse mammary tumor
virus (MMTV) were present in 38% of the breast cancers studied from American
women and were not detectable in non-tumor breast tissue from the same patient.
The entire proviral structure was described and viral particles were isolated
from primary cultures of human breast cancer. This virus was designated as human
mammary tumor virus (HMTV). Hormone response elements present in the HMTV Long
Terminal-Repeat (LTR) suggest a mechanism for association of HMTV with hormonally
responding tissues. In fact, the incidence of HMTV sequences is higher in
gestational breast cancers, which are associated with hormonal changes. Milk
epithelial cells are also under hormonal regulation and therefore are excellent
specimens for HMTV sequence detection. METHODS: The HMTV sequence was studied in
milk samples from lactating women recruited with increased risk of breast cancer
because they had undergone breast biopsies (Biopsy-Group) and lactating women
without breast biopsies (Reference-Group). RESULTS: HMTV-env sequences were
detected by PCR in milk of 7.61% of 92 women of the Reference-Group and in 20.55%
of 73 women of the Biopsy-Group (p: 0.015). The sequences were 94-98% homologous
to MMTV. HMTV-env and HMTV-env/LTR junction sequences were detected in high-speed
pellet RNA, implying the presence of HMTV viral particles. PCR assays to detect
the murine mitochondrial cytochrome oxidase gene and intracisternal-A-type
particle sequences were performed to rule out mouse mitochondrial or genomic DNA
contamination. Eight women of the 73 Biopsy-Group participants had breast cancer
and the milk of only one of these eight women had HMTV-env sequences. In the
remaining 65 women of the Biopsy-Group, under enough clinical suspicion to lead
to biopsy, HMTV was detected in 14, nearly three times the number of milks as
compared to the Reference-Group (21.54% versus 7.61%; p: 0.016). CONCLUSION: The
significance of HMTV in milk from the Reference-Group, the greater frequency in
the milk of women who had undergone a breast biopsy and its possible infectivity
for infants are important questions under study. The similarity of HMTV to MMTV
is striking and suggests one possible avenue for viral transmission in humans.
PMID- 25120583
TI - A simple structure-based model for the prediction of HIV-1 co-receptor tropism.
AB - BACKGROUND: Human Immunodeficiency Virus 1 enters host cells through interaction
of its V3 loop (which is part of the gp120 protein) with the host cell receptor
CD4 and one of two co-receptors, namely CCR5 or CXCR4. Entry inhibitors binding
the CCR5 co-receptor can prevent viral entry. As these drugs are only available
for CCR5-using viruses, accurate prediction of this so-called co-receptor tropism
is important in order to ensure an effective personalized therapy. With the
development of next-generation sequencing technologies, it is now possible to
sequence representative subpopulations of the viral quasispecies. RESULTS: Here
we present T-CUP 2.0, a model for predicting co-receptor tropism. Based on our
recently published T-CUP model, we developed a more accurate and even faster
solution. Similarly to its predecessor, T-CUP 2.0 models co-receptor tropism
using information of the electrostatic potential and hydrophobicity of V3-loops.
However, extracting this information from a simplified structural vacuum-model
leads to more accurate and faster predictions. The area-under-the-ROC-curve (AUC)
achieved with T-CUP 2.0 on the training set is 0.968+/-0.005 in a leave-one
patient-out cross-validation. When applied to an independent dataset, T-CUP 2.0
has an improved prediction accuracy of around 3% when compared to the original T
CUP. CONCLUSIONS: We found that it is possible to model co-receptor tropism in
HIV-1 based on a simplified structure-based model of the V3 loop. In this way,
genotypic prediction of co-receptor tropism is very accurate, fast and can be
applied to large datasets derived from next-generation sequencing technologies.
The reduced complexity of the electrostatic modeling makes T-CUP 2.0 independent
from third-party software, making it easy to install and use.
PMID- 25120586
TI - Correlation study on adiponectin gene SNP45 and long-term oxidative stress in
patients with diabetes and carotid atherosclerosis.
AB - The aim of the present study was to investigate the correlation between the
adiponectin gene single nucleotide polymorphism (SNP)45 T/G and long-term
oxidative stress in type II diabetes mellitus (T2DM) patients with carotid
atherosclerosis. Patients with T2DM were divided into non-carotid atherosclerosis
and carotid atherosclerosis groups, which were then subsequently divided into TT
and TG + GG groups according to the adiponectin SNP45 T/G genotypes. Enzyme
linked immunosorbent assay, TaqMan probe quantitative polymerase chain reaction
(PCR), PCR-TaqMan, color Doppler and other methods were used to determine the
adiponectin levels, gene polymorphisms, acquired mitochondrial DNA (mtDNA) A3243G
somatic cell mutation rates and the carotid intima-media thickness. The somatic
cell mutation rate of acquired mtDNA A3243A/G in the T2DM carotid atherosclerosis
group was significantly higher compared with the group without carotid
atherosclerosis. In addition, the acquired mtDNA A3243A/G somatic cell mutation
rate in the T2DM carotid atherosclerosis group with the adiponectin gene SNP45 TT
genotype was significantly lower compared with the SNP45 TG/GG genotype group.
T2DM combined with carotid atherosclerosis was associated with long-term
oxidative stress. In addition, adiponectin gene SNP45 T/G was associated with
increased mtDNA A3243A/G somatic mutation rates in T2DM patients with carotid
atherosclerosis. Therefore, adiponectin gene polymorphisms may lead to diabetes
atherosclerosis through oxidative stress.
PMID- 25120587
TI - Correlation between cystathionine beta-synthase T883C genetic polymorphism and
primary hypertension.
AB - The present study aimed to investigate the correlation between cystathionine beta
synthase (CBS) T833C polymorphisms and primary hypertension. A case-control study
was conducted by genotyping the representative variation in 545 hypertensive
individuals (aged 49.23+/-7.56 years) and 500 normotensive individuals (aged
49.90+/-10.01 years). The T833C genetic polymorphisms of the CBS enzyme were
detected in all subjects by amplification refractory mutation system polymerase
chain reaction (PCR) analysis. The CBS T833C polymorphism was successfully
genotyped in the general population with a sample size of 1,045 (545+500)
individuals. The genotypic and allelic frequency distributions of the CBS T833C
polymorphism were not significantly different between the hypertensive and
normotensive groups (P>0.05). The CC genotype was significantly different
(P<0.05) from the CT and TT genotypes in terms of body mass index (BMI), and the
levels of triglycerides (TG) and homocysteine (Hcy). Multiple logistic regression
analysis revealed that BMI, total cholesterol (TC) level, smoking, plasma Hcy
level and a family history of hypertension were the independent risk factors for
hypertension in the population studied. The results indicate that the level of
plasma Hcy was a risk factor for hypertension in the population studied. However,
the mutation of the CBS T833C gene was not concluded to be an important
hereditary factor for influencing the level of plasma Hcy.
PMID- 25120585
TI - Summary of the various treatments for osteonecrosis of the femoral head by
mechanism: A review.
AB - Osteonecrosis of the femoral head (ONFH), also known as femoral head avascular
necrosis, is a pathological state with a number of possible etiologies including
steroid administration, alcohol abuse, traumatic events, vascular injury and
idiopathic origins. ONFH causes a reduction in the vascular supply to the
subchondral bone of the femoral head, which results in osteocyte death and the
collapse of the articular surface. Treatments for ONFH include non-weight-bearing
therapy, physical support, the promotion of osteoclast apoptosis, and the
reduction of osteoblast and osteocyte apoptosis. The aim of the present review
was to summarize the treatments for ONFH by mechanism from a new perspective and
to describe the condition with an emphasis on treatment options.
PMID- 25120588
TI - Objective parameters aid the prediction of fistulas in pancreatic surgery.
AB - Insufficiency of pancreatic anastomosis with leakage from the pancreatic stump
and the development of fistulas account for the majority of surgical
complications following pancreatic resection, which are often life threatening.
The cause of pancreatic fistulas of the remnant tissue on a molecular level
remains unclear. Thus, the aim of the present study was to investigate risk
factors associated with postoperative pancreatic fistula (POPF) formation and to
define parameters that may predict the resection outcome. Pancreatic resection
margins were selected from 31 patients, including 16 individuals without and 15
patients with POPF, to analyze the degree of fibrosis, lipomatous atrophy,
inflammatory activity and infiltration. Wound healing factors were assessed by
luminex technology using tissue homogenates, while the distribution in situ was
assessed using immunohistochemistry. Increased chronic inflammatory infiltration,
a higher degree of fibrosis and a reduction in lipomatous atrophy were observed
in the samples without anastomotic fistulas. Multiplex analysis of 38 wound
healing factors demonstrated significantly higher levels of interleukin (IL)-6,
8 and -12, glucagon-like peptide-1 and matrix metalloproteinase (MMP)-1, -2, -3
and -12 in the group without fistulas, while lower concentrations of IL-10, IL-17
and gastric inhibitory polypeptide were observed. Therefore, the observations of
the present study indicated that increased inflammatory infiltration and
inflammatory activity, as well as higher concentrations of proinflammatory
cytokines and higher MMP levels at the resection margins, predisposed individuals
to a lower fistula incidence rate following pancreatic resection.
PMID- 25120589
TI - Protective effects of quercetin and hyperoside on renal fibrosis in rats with
unilateral ureteral obstruction.
AB - Prevention of renal fibrosis is an important therapeutic strategy in the
treatment of obstructive nephropathy. The purpose of the present study was to
identify whether the combination of two natural plant-derived flavanoids,
quercetin and hyperoside (QH), could inhibit renal fibrosis in the model of
unilateral ureteral obstruction (UUO) in rats. QH mixtures (1:1) were fed to
Wistar rats, and UUO ligation was performed on all the rats with the exception of
the sham group. Masson's trichrome staining was used for interstitial fibrosis,
while immunohistochemistry and western blot analysis were used to detect the
expression of alpha-smooth muscle actin (SMA) and fibronectin (FN). In the QH
group, the expression of SMA and FN was significantly lower than that in the
untreated UUO group. In addition, QH administration significantly inhibited the
SMA and FN expression of mesangial cells induced by interleukin-1beta.
Consequently, it was evident that combinational QH therapy prevented UUO-induced
renal fibrosis. Based on these findings, the combinatorial intervention of
phytomedicine may present an improved treatment strategy for renal fibrotic
disease.
PMID- 25120590
TI - Lentivirus vector-mediated mitofusin-2 overexpression in rat ovary changes
endocrine function and promotes follicular development in vivo.
AB - The aim of the present study was to evaluate the expression and effect of rat
mitofusin-2 (rMfn2) in the ovaries and other organs in rats. Rat models were
developed by the intraovarian microinjection of an rMfn2-overexpressing
lentiviral vector. Lenti-green fluorescent protein (GFP)-rMfn2 was microinjected
into rat ovaries at a dosage of 2*106 tuberculin units virosome (n=25) and lenti
GFP was microinjected as a control (n=25). The expression of rMfn2 in the ovaries
and other tissues was observed by fluorescence microscopy on days 7, 15, 30, 45
and 60 after the microinjection (n=5/day from each group). The serum levels of
estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH) and
luteinizing hormone (LH) were determined by radioimmunoassay. Western blotting
was used for the quantitative analysis of the expression of rMfn2 and the
progesterone receptor (PR), estradiol receptor (ER), luteinizing hormone receptor
(LHR) and follicle-stimulating hormone receptor (FSHR). The expression of rMfn2
was detected on day 7 after infection, increased with time and was maintained
efficiently until day 60. In addition, rMfn2 was highly expressed in the
fallopian tubes, uterus, cardiac muscle, liver and kidney, but expressed at a low
level in adipose tissue. The serum levels of E2 and P in the model group were
significantly increased compared with those in the control group, whereas the FSH
and LH levels showed no significant difference between groups. The expression
levels of the ER and PR in the model group were higher than those in the control
group; however, no significant difference was observed between groups for the
expression levels of LHR and FSHR. These findings suggest that the intraovarian
microinjection of lenti-GFP-rMfn2 resulted in a significant time-dependent
overexpression of rMfn2 in various organs, and that rMfn2 overexpression in rat
ovaries changed the endocrine function and promoted follicular development.
PMID- 25120584
TI - Current animal models of bladder cancer: Awareness of translatability (Review).
AB - Experimental animal models are crucial in the study of biological behavior and
pathological development of cancer, and evaluation of the efficacy of novel
therapeutic or preventive agents. A variety of animal models that recapitulate
human urothelial cell carcinoma have thus far been established and described,
while models generated by novel techniques are emerging. At present a number of
reviews on animal models of bladder cancer comprise the introduction of one type
of method, as opposed to commenting on and comparing all classifications, with
the merits of a certain method being explicit but the shortcomings not fully
clarified. Thus the aim of the present study was to provide a summary of the
currently available animal models of bladder cancer including transplantable
(which could be divided into xenogeneic or syngeneic, heterotopic or orthotopic),
carcinogen-induced and genetically engineered models in order to introduce their
materials and methods and compare their merits as well as focus on the
weaknesses, difficulties in operation, associated problems and translational
potential of the respective models. Findings of these models would provide
information for authors and clinicians to select an appropriate model or to judge
relevant preclinical study findings. Pertinent detection methods are therefore
briefly introduced and compared.
PMID- 25120591
TI - Clinical analysis and etiology of porokeratosis.
AB - The present study was performed in order to define the clinical manifestations of
porokeratosis, with particular emphasis on genital porokeratosis. A total of 55
cases of porokeratosis were retrospectively reviewed between 2000 and 2007 from
Huashan Hospital (Shanghai, China). Out of 55 cases, there were 22 cases of
porokeratosis of Mibelli, 17 cases of disseminated superficial actinic
porokeratosis (DSAP), 15 cases of disseminated superficial porokeratosis and one
case of linear porokeratosis. The ratio of males to females was 39:16. Among
them, 12 cases had a family history of porokeratosis. During the five-year follow
up period, no malignant transformation was observed and no further aggravation of
lesions was detected. The results indicated that the initial region of DSAP in
the Chinese population may differ from Caucasians. In combination with other
studies, the present study found that genital porokeratosis in the Chinese
population is often associated with pruritus. Since no recurrence was observed in
cases treated with surgical excision, it was suggested that surgical excision is
a viable treatment strategy and should be used for porokeratotic lesions if
possible. In addition, regular follow-ups are required, since the aggravation of
porokeratosis may cause the development of malignancy transformation.
PMID- 25120592
TI - Preclinical humanized mouse model with ectopic ovarian tissues.
AB - The aim of the present study was to establish human ovarian stroma within the
mouse subcutaneously, in order for the resulting stroma to serve as a useful
preclinical tool to study the progression of human ovarian cancer in a humanized
ovarian microenvironment. Normal human ovarian tissues were subcutaneously
implanted into severe combined immunodeficient (SCID) mice and then the implants
were identified by immunohistochemistry. The implants became vascularized and
retained their original morphology for about 4 weeks following implantation.
Immunohistochemical staining for cytokeratin-7 confirmed the ovarian origin of
the epithelial cells. CD34 staining demonstrated human-derived vessels. Positive
estrogen receptor and partially-positive progesterone receptor staining indicated
the estrogen and progesterone dependence of the implants. Only vascular pericytes
expressed alpha-smooth muscle actin, indicating the normal ovarian origin of the
xenografts. Human ovarian tissue successfully survived in SCID mice and retained
its original properties. This humanized mouse model may be used as preclinical
tool to investigate ovarian cancer.
PMID- 25120593
TI - MicroRNA expression profile in intrauterine hypoxia-induced pulmonary hypoplasia
in rats.
AB - Hypoxia is necessary for fetal development; however, excess hypoxia is
detrimental. The mechanisms underlying the effects of hypoxia on lung development
remain unclear, although important roles of microRNAs (miRNAs) during lung
development have recently been established. However, the effect on lung
development at an miRNA expression level, following changes in oxygen tension,
have not yet been studied. In the present study, pregnant rats were exposed to a
fraction of inspired oxygen of 10.5 or 21% for two days on gestation day 19,
following which the body weight, lung wet weight, radial alveolar count (RAC) and
mean linear intercept (Lm) of the newborn pups were analyzed on postnatal day 1.
To define the role of miRNAs during lung development following intrauterine
hypoxia exposure, the miRNA expression pattern was profiled using a miRNA
microarray. The newborn rats in the hypoxic group exhibited statistically
significant decreases in body weight, lung weight and the RAC, as well as a
marked increase in the Lm. A total of 69 miRNAs were identified to have
significant changes in expression, including 55 upregulated and 14 downregulated
miRNAs. Quantitative polymerase chain reaction was used to validate the
microarray results of six selected miRNAs. Therefore, the results indicated that
late gestation intrauterine hypoxia exposure may cause lung injury and miRNAs may
play important roles in this process.
PMID- 25120594
TI - Comparison of the radiosensitivities of neurons and glial cells derived from the
same rat brain.
AB - Non-proliferating cells, such as mature neurons, are generally believed to be
more resistant to X-rays than proliferating cells, such as glial and vascular
endothelial cells. Therefore, the late adverse effects of radiotherapy on the
brain have been attributed to the radiation-induced damage of glial and vascular
endothelial cells. However, little is known about the radiosensitivities of
neurons and glial cells due to difficulties in culturing these cells,
particularly neurons, independently. In the present study, primary dissociated
neurons and glial cultures were prepared separately from the hippocampi and
cerebrum, respectively, which had been obtained from the same fetal rat on
embryonic day 18. X-irradiations of 50 Gy were performed on the cultured neurons
and glial cells at 7 and 21 days in vitro (DIV). The cells were fixed at 24 h
after irradiation. Terminal deoxynucleotidyl transferase-mediated dUTP nick end
labeling was then performed to measure the apoptotic indices (AIs). The AIs of
non-irradiated and irradiated neurons at 7 DIV were 23.7+/-6.7 and 64.9+/-4.8%,
and those at 21 DIV were 52.1+/-17.4 and 44.6+/-12.5%, respectively. The AIs of
non-irradiated and irradiated glial cells at 7 DIV were 5.8+/-1.5 and 78.4+/-3.3%
and those at 21 DIV were 9.6+/-2.6 and 86.3+/-4.9%, respectively. Glial cells and
neurons were radiosensitive at 7 DIV. However, while glial cells were
radiosensitive at 21 DIV, neurons were not.
PMID- 25120595
TI - Elevated levels of alanine transaminase and triglycerides within normal limits
are associated with fatty liver.
AB - In the present study, the threshold values of laboratory data for the diagnosis
of non-alcoholic fatty liver disease (NAFLD) were investigated. The study
enrolled patients who had undergone abdominal ultrasound (US) between April 2013
and August 2013, and for whom laboratory data were available on the same day.
NAFLD was diagnosed following observations of a bright liver or hepatorenal echo
contrast on the abdominal US scans. Patients were excluded from the study if they
had liver diseases or had been prescribed prednisolone or methotrexate. Receiver
operating characteristic curves, the Wilcoxon signed-rank test and Fisher's exact
probability test were used for data analysis. In total, 80 NAFLD and 94 non-NAFLD
patients were enrolled in the study. The threshold levels of alanine
aminotransferase (ALT) and triglyceride (TG) for the diagnosis of NAFLD were 19.0
IU/l and 101 mg/dl, respectively. Patients were divided into two groups according
to the levels of ALT and TG. Those with ALT levels of >19 IU/l and TG levels of
>101 mg/dl were defined as the positive group, while the remaining patients were
classified as the negative group. The specificity and positive predictive value
using the combined threshold levels of ALT >19 IU/l and TG >101 mg/dl were 80.9
and 75.0%, respectively. Therefore, the results indicated that ALT levels of >19
IU/l or TG levels of >101 mg/dl were useful markers for the screening of NAFLD.
However, NAFLD was more strongly suspected in patients with ALT levels of >19
IU/l and TG levels of >101 mg/dl.
PMID- 25120596
TI - Long-term follow-up of whole lung lavage in patients with pulmonary alveolar
proteinosis.
AB - Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by intra
alveolar accumulation of lipid and proteinaceous material. While a small subset
of patients with PAP spontaneously improve or even undergo disease remission, the
majority of patients develop persistent or progressive disease. Numerous
therapies have been used to treat PAP over the years; however, at present, whole
lung lavage (WLL) remains the gold standard treatment for PAP. In the present
study, data were accumulated from a cohort of patients with PAP (n=11) between
2003 and 2011 at the Wuxi People's Hospital Affiliated to Nanjing Medical
University. The disease affected males and females with a ratio of 2.7:1 and all
the males were current or previous smokers. The disease severity score (DSS) of
the patients was mainly distributed in DSS 4 or DSS 5. All the patients underwent
WLL at least once, with one patient undergoing WLLs twice and another patient
three times. The clinical features, arterial blood gas and pulmonary function of
the patients, were assessed prior to and following the lavage. WLL resulted in a
significant improvement in symptoms, radiographic features, PaO2, D(A-a)O2 and
DLCO in patients with PAP, while pulmonary ventilation function did not
significantly improve. WLL appears to be an effective approach for the treatment
of PAP and leads to an improvement in survival rate.
PMID- 25120597
TI - Helicobacter pylori infection promotes the invasion and metastasis of gastric
cancer through increasing the expression of matrix metalloproteinase-1 and matrix
metalloproteinase-10.
AB - The aim of this study was to investigate the effect and mechanism of Helicobacter
pylori infection in the invasion and metastasis of gastric cancer. Specimens from
80 patients with gastric cancer (of which 20 patients had metastatic gastric
cancer) and 40 patients with chronic gastritis were included in this study. H.
pylori infection was determined by ELISA and the expression of matrix
metalloproteinase-1 (MMP-1) and MMP-10 was observed using immunohistochemistry.
The correlation between H. pylori infection and the clinical pathological
features of gastric cancer was analyzed by SPSS 13.0 software. The protein
expression levels of MMP-1 and MMP-10 in MGC-803 cells infected with H. pylori
were analyzed using western blotting. H. pylori infection was found in 62 of the
80 patients with gastric cancer and in 13 of the 40 patients with chronic
gastritis. In addition, H. pylori infection was correlated with the staging and
lymph node metastasis, but not with the gender, age and histological types of
patients. H. pylori infection was also significantly correlated with the
expression of MMP-1 and MMP-10 (r=0.8718, P<0.05 and r=0.5477, P<0.05,
respectively). The expression of MMP-1 and MMP-10 was significantly upregulated
following induction by H. pylori infection (P<0.05), with significant effects
occurring following infection for 12 and 6 h, respectively. H. pylori infection
may promote the invasion and metastasis of gastric cancer by increasing the
expression of MMP-1 and MMP-10.
PMID- 25120598
TI - DNA methylation of microRNA-375 in impaired glucose tolerance.
AB - In the present study, the expression levels and DNA methylation status of
microRNA (miRNA)-375 in patients with impaired glucose tolerance (IGT) and type 2
diabetes mellitus (T2DM) were analyzed and the role of DNA methylation of miRNA
375 in the pathogenesis of T2DM was investigated. Compared with the miR-375
levels in patients with normal glucose tolerance (NGT; n=53), the samples from
patients with IGT (n=44) exhibited downregulation of miR-375, while those from
patients with T2DM (n=54) exhibited upregulation of miR-375 in the plasma.
Additionally, the samples from patients with IGT were observed to be
hypermethylated compared with those from patients with T2DM and NGT (P=0.042).
Analysis of three CpG units (CpG1.2, CpG20 and CpG25.26.27) from 17 CpG sites
(between -990 and -1,258 bp, relative to the transcription start site) revealed
higher methylation levels in patients with IGT compared with those in patients
with NGT (P<0.05). The methylation of two CpG units (CpG1.2 and CpG25.26.27) was
higher in patients with IGT than in the patients with T2DM (P<0.05). Thus, the
present study demonstrated that the miR-375 promoter was hypermethylated and the
levels of miR-375 in the plasma were downregulated in the patients with IGT. DNA
hypomethylation may have an important role in the regulation of miR-375
expression and may contribute to the pathogenesis of T2DM.
PMID- 25120599
TI - Characteristics and risk factor analysis of 410 cases of tracheobronchial
tuberculosis.
AB - The present study analyzed the characteristics and risk factors associated with
tracheobronchial tuberculosis (TBTB) in 410 patients with TBTB. Retrospective
analysis was performed on the clinical features, bronchoscopy performance,
bacteriological examination, imaging and treatment of 410 patients who were
diagnosed with TBTB using bronchoscopy. Among the 410 patients, 10 patients
underwent chest X-ray which revealed two cases of atelectasis, eight cases of
patch or spot shadows, three cases of cavity, one case of nodule and one case
with no abnormalities. The remaining 400 patients underwent computed tomography
chest scans and/or airway reconstruction examinations. Among all the lesion
types, the cavity type was found to be the most likely to cause bronchial
stenosis or obstruction, with statistically significant differences when compared
with the congestion, stenosis or scar lesion types (P<0.01). Moreover, for the
cavity type, there were 194 sites of obstruction prior to therapy; however, only
23 sites of obstruction remained following therapy. Furthermore, there were 34
sites without stenosis prior to therapy and 205 sites without stenosis following
therapy. The number of sites of obstruction was significantly decreased and the
number of sites without stenosis was increased upon therapy. These findings
suggest that the cavity type is the most sensitive type to therapy among the five
types of TBTB lesion.
PMID- 25120601
TI - Diagnosis of the cavo-hepato-atrial pathway in Budd-Chiari syndrome by
ultrasonography.
AB - The aim of this study was to investigate the ultrasonic features of the cavo
hepato-atrial pathway in Budd-Chiari syndrome (BCS), by which blood is drained
from the occluded inferior vena cava (IVC) to the right atrium via hepatic veins.
Ultrasonograms from 11 patients with BCS with cavo-hepato-atrial pathways were
retrospectively studied. Doppler ultrasound was used to observe the direction of
the flow and measure the velocity of the blood-draining vessels. Blood flow in
the draining vessels and the collaterals was shown as blue, red or bicolored
depending on whether the flow direction was away from the transducer, towards the
transducer or both. For measurement, the Doppler angle between the axis of the
Doppler beam and that of the vein examined was always <60 degrees .
Ultrasonography was performed 1-2 weeks prior to digital subtraction angiography
(DSA). All patients were confirmed by DSA. Membranous and segmental occlusions of
IVCs were observed in seven and four cases, respectively. Blood flow from the IVC
reversed to the hepatic/accessory hepatic vein, continued through the dilated
intrahepatic collaterals, onward to the other hepatic vein and finally to the
right atrium. The majority of the inlets (8/11) of hepatic veins above the
occlusion were narrow compared with the dilated distant parts of the lumens.
Accelerated blood flow in the inlets was detected in all patients regardless of
the luminal diameter. In conclusion, the results from the present study suggest
that the unusual cavo-hepato-atrial pathway can be diagnosed reliably by
ultrasonography, which may be useful for clinical management.
PMID- 25120600
TI - Fistular onion stalk extract exhibits anti-atherosclerotic effects in rats.
AB - Fistular onion stalk is used as a traditional herbal medicine, and its extract
exhibits certain beneficial effects on cardiovascular disease. In this study, the
effects of fistular onion stalk extract on the pathological features, circulating
inflammatory cytokines, local renin-angiotensin-aldosterone system (RAAS) and
signaling pathway activities were examined using an in vivo model of
atherosclerosis. Atherosclerosis of the aorta was induced by loading Sprague
Dawley rats with a high-fat diet and vitamin D2. Fistular onion stalk extract
administration began five weeks after the induction of atherosclerosis and
continued for 12 weeks. Rats treated with fistular onion stalk extract showed a
significant reduction in the pathological region compared with the vehicle
treated controls. Inhibition of atherosclerosis was associated with preservation
of the vascular wall and immune cell infiltration. The extract also reduced the
levels of the local inflammatory cytokines interleukin (IL)-1beta, IL-6, monocyte
chemoattractant protein-1 and tumor necrosis factor-alpha. Furthermore, the
extract downregulated the local activity of the RAAS. In addition, extract
treatment inhibited several inflammatory signaling pathways by preventing
phosphorylation, including the nuclear factor kappaB, Janus kinase/signal
transducers and activators of transcription and mitogen-activated protein kinase
pathways. These data indicate that fistular onion stalk extract may be useful for
the attenuation of atherosclerosis, and the mechanism includes the regulation of
the local inflammatory response.
PMID- 25120602
TI - Diagnosis and management of a patient with primary pulmonary diffuse large B-cell
lymphoma: A case report and review of the literature.
AB - Primary pulmonary lymphoma (PPL) is an uncommon type of non-Hodgkin's lymphoma.
The majority of PPLs are of low-grade, mucosa-associated lymphoid tissue type.
Primary pulmonary diffuse large B-cell lymphoma (DLBCL) is extremely rare, and
prompt diagnosis may be challenging since its clinical symptoms and signs are
nonspecific. Although the clinical features, diagnostic procedures, optimal
management and prognostic factors of this disease have not yet been well defined,
open thoracotomy and chest computed tomography (CT)-guided percutaneous biopsy
are the preferred methods used in previous studies. In the present case report,
the diagnosis and management of a patient with primary pulmonary DLBCL is
reported. A 68-year-old patient was admitted to hospital in May 2013, with
complaints of shortness of breath and intermittent wheezing and a cough
associated with the production of small amounts of phlegm. Following admission,
chest CT scans revealed a mass in the right middle lobe with ground-glass
opacities at the lesion margins, as well as air bronchograms in the areas of
consolidation. Bronchoscopy was performed and revealed an endobronchial lesion
and partial stenosis in the distal end of the middle segment bronchus.
Transbronchial needle aspiration (TBNA) of the right hilar lymph node, as well as
endobronchial biopsy, was performed. The patient was diagnosed with primary
pulmonary DLBCL by subsequent histopathological and immunohistochemical analysis
of biopsy specimens collected via TBNA. Following the final diagnosis, standard
treatment with CHOP chemotherapy resulted in significant clinical and
radiological response and the patient remained in remission 8 months later. These
results indicate that TBNA may be an effective method for the diagnosis of
primary pulmonary DLBCL.
PMID- 25120603
TI - Post-transplant recurrent pericarditis with pericardial tamponade is successfully
treated with colchicine: A case report.
AB - Recurrent pericarditis is a rare complication following renal transplantation.
Colchicine, an inhibitor of microtubule polymerization, has been recommended for
the treatment of recurrent acute pericarditis in non-transplant patients and is
commonly used for the treatment of gout in transplant patients. However, the use
of colchicine for the treatment of recurrent pericarditis in renal transplant
patients has rarely been reported. In the present study, a rare case of recurrent
pericarditis, manifested as large pericardial effusion and pericardial tamponade
within the first year following renal transplantation, was successfully treated
with colchicine. Therefore, low-dose colchicine may be a safe and effective
option for the treatment of recurrent pericarditis in renal transplant patients.
PMID- 25120604
TI - Whole bone marrow cell culture: A convenient protocol for the in vitro expansion
of endothelial progenitor cells.
AB - The number and function of endothelial progenitor cells (EPCs) may be a
predictive factor for the severity and outcome of cardiovascular disease.
However, the manipulation of bone marrow mononuclear cell (BMMC) cultures for
EPCs is an elaborate and difficult procedure in small experimental animals. The
present study aimed to assess the feasibility of whole bone marrow cell (WBMC)
culture for expanding EPCs in small experimental animals. C57BL/6 mice (age, 3-4
weeks; weight, 9.47+/-0.76 g) were used as the experimental animals, and WBMCs
were isolated from the femora and tibiae and cultured in endothelial cell growth
medium-2. A BMMC culture for EPCs was used as a control. EPC growth, phenotype
and functions were assessed in vitro and in vivo. The results demonstrated that
EPCs were easily obtained from a WBMC culture in vitro. The cells exhibited
similar growth and biological characteristics when compared with the EPCs derived
from the traditional BMMC culture system. Thus, the cells were able to
simultaneously bind to lectin and cause phagocytosis of acetylated-low density
lipoproteins. In addition, the cells exhibited high expression levels of cluster
of differentiation 34 and fetal liver kinase 1, and possessed similar functional
properties to BMMC-derived EPCs, including vascular network formation,
proliferation, adhesion and migration abilities in vitro. Thus, WBMC-derived EPCs
can improve the outcome of pulmonary vascular disease when transplanted into a
monocrotaline-induced pulmonary hypertension mouse model. The results of the
present study indicated that the WBMC culture system is a more convenient and
effective method of obtaining and expanding EPCs compared with BMMC culture, with
the advantage of a simplified procedure.
PMID- 25120605
TI - Identification of genes in HepG2 cells that respond to DNA methylation and
histone deacetylation inhibitor treatment.
AB - Previous studies have demonstrated that epigenetics has an important role in the
regulation of gene expression in cancer. Epigenetics is the study of reversible,
heritable changes in gene function, which occur independently from changes in the
DNA sequence. DNA methylation and histone deacetylation are the two most
important epigenetic modifications. DNA methylation was one of the first
discovered epigenetic modifications and it may lead to changes in chromatin
structure, DNA conformation and DNA stability, thereby controlling gene
expression. Sample data on the HepG2 cell line from the Gene Expression Omnibus
database under GSE5230 accession number were obtained and GEOquery and the limma
package were then used to analyze the data and identify differentially expressed
genes using Gene Otology. This was conducted in order to investigate the effect
on gene expression of inhibiting DNA methylation and histone deacetylation, and
to explore the potential role of epigenetics in the development and treatment of
hepatic carcinoma. It was found that inhibition of DNA methylation and histone
deacetylation affected not only substance metabolism, but also the immune
activity in HepG2 cells. Furthermore, common target sites for transcription
factors were identified in the differentially expressed genes. It may be
concluded that the inhibition of DNA methylation and histone deacetylation
contributes to the treatment of hepatic carcinoma and may provide a novel
therapeutic strategy for the treatment of hepatic cancer.
PMID- 25120607
TI - A patient with agranulocytosis following the discontinuation of methimazole
treatment for 4 months: A case report.
AB - Agranulocytosis is a rare and serious adverse effect of antithyroid drugs (ATD),
in particular methimazole (MMI), and usually develops within 3 months following
the start of uninterrupted ATD treatment. Agranulocytosis may also develop for
the first time following interruption and subsequent resumption of the same ATD
treatment. In this case report, a 27-year-old female, who was treated for
thyrotoxicosis with MMI, developed agranulocytosis following the discontinuation
of MMI treatment for four months. To the best of our knowledge, this is the first
study to report this. The aim of this report is to increase the awareness of
physicians of the onset of agranulocytosis when MMI is discontinued, and to
demonstrate that MMI should be used with caution.
PMID- 25120606
TI - Prognostic significance of artemin and GFRalpha1 expression in laryngeal squamous
cell carcinoma.
AB - Artemin (ARTN) has been implicated in the development and progression of several
human malignancies. However, the clinical and prognostic significance of ARTN and
its receptors has not yet been investigated in human laryngeal squamous cell
carcinoma (LSCC). Therefore, in the present study, the protein expression of ARTN
and its receptor, namely GFRalpha1, was determined in 76 LSCC and 26 laryngeal
polyp tissue samples using immunohistochemistry. Furthermore, the
clinicopathological and prognostic significance of ARTN and GFRalpha1 expression
was analyzed in patients with LSCC. The results revealed that the expression of
ARTN and GFRalpha1 was significantly increased in LSCC compared with polyp tissue
samples. Furthermore, the expression of ARTN and GFRalpha1 was positively
associated with pTNM stage in LSCC. Kaplan-Meier survival analyses revealed a
strong association between the expression of ARTN or GFRalpha1 and the survival
of patients with LSCC. Correlation analysis demonstrated that the expression of
ARTN was significantly correlated with the expression GFRalpha1. In conclusion,
the results demonstrated that ARTN and GFRalpha1 may be useful predictors of
disease progression and outcome in patients with LSCC.
PMID- 25120608
TI - Iron regulates the expression of ferroportin 1 in the cultured hFOB 1.19
osteoblast cell line.
AB - Iron metabolism is tightly regulated in osteoblasts, and ferroportin 1 (FPN1) is
the only identified iron exporter in mammals to date. In the present study, the
regulation of FNP1 in human osteoblasts was investigated following various iron
treatments. The human osteoblast cell line hFOB 1.19 was treated with ferric
ammonium citrate (FAC) or desferrioxamine (DFO) of various concentrations. The
intracellular iron ion levels were measured using a confocal laser scanning
microscope. In addition, the mRNA and protein expression levels of FPN1 were
detected by quantitative polymerase chain reaction, western blot analysis and
immunofluorescence. The results demonstrated that increasing iron concentrations
via FAC treatment increased the expression of FPN1. By contrast, decreasing the
iron concentration by DFO treatment decreased FNP1 expression levels. In addition
to demonstrating that the FNP1 expression changed according to the iron
concentration, the observations indicated that changes in FPN1 expression may
contribute to the maintenance of the intracellular iron balance in osteoblasts.
PMID- 25120609
TI - Unilateral ovarian and fallopian tube agenesis in an infertile patient with a
normal uterus.
AB - Congenital agenesis of the unilateral adnexa is a condition that has rarely been
described in the literature. The current study presents the case of a 26-year-old
female who was admitted to the Department of Gynecology at the Women's Hospital
of Zhejiang University (Hangzhou, Zhejiang) for primary infertility. The patient
was diagnosed with unilateral ovarian and fallopian tubal agenesis, without
malformations of the uterus and urinary tract, during diagnostic laparoscopy and
hysteroscopy. A literature review was conducted with the aim of determining the
possible causes of these anomalies. However, the etiology of the adnexal anomaly
remained unclear, although torsion or congenital defects were the most likely
explanation. Therefore, the observations of the present study indicate that
contralateral tubal pathologies may contribute to sterility.
PMID- 25120610
TI - The effect of the Ras homolog gene family (Rho), member A/Rho associated coiled
coil forming protein kinase pathway in atrial fibrosis of type 2 diabetes in
rats.
AB - Diabetes mellitus promotes atrial structural remodeling, thereby producing atrial
arrhythmogenicity. Atrial arrhythmia can substantially increase the risk of
premature death. The aim of this study was to investigate the role of Ras homolog
gene family, member A (RhoA)/Rho associated coiled-coil forming protein kinase
(ROCK) in atrial fibrosis in diabetic hearts, and the effects of fasudil
hydrochloride hydrate on atrial fibrosis. An eight-week-old male Sprague-Dawley
rat model of type 2 diabetes was established using a high-fat diet combined with
streptozotocin [30 mg/kg, once, intraperitoneal (i.p.)]. Animals were randomly
divided into three groups: Control rats, untreated diabetic rats that received
vehicle, and treated diabetic rats that received Rho kinase inhibitor fasudil
hydrochloride hydrate (10 mg/kg/day, i.p., for 14 weeks). The morphological
features of atrial fibrosis were observed using Masson staining. The mRNA
expression levels of RhoA, ROCK1, ROCK2, type-I and type-III procollagen were
assessed with quantitative polymerase chain reaction. The protein levels of RhoA,
ROCK1 and ROCK2 were evaluated using western blot analysis. The atria of
untreated diabetic rats showed evident atrial fibrosis as compared to the control
rats; the mRNA expression levels of RhoA, ROCK1, ROCK2, type-I and type-III
procollagen were upregulated; and the protein levels of RhoA, ROCK1 and ROCK2
were increased. The treatment with fasudil hydrochloride hydrate significantly
reduced atrial fibrosis, mRNA levels of RhoA, ROCK1, ROCK2, type-I and type-III
procollagen, and the protein levels of RhoA, ROCK1 and ROCK2. The results
suggested that RhoA/ROCK was involved in atrial fibrosis, and that fasudil
hydrochloride hydrate ameliorates atrial fibrosis through the RhoA/ROCK pathway
in rats with type 2 diabetes.
PMID- 25120611
TI - Calcifying aponeurotic fibroma of the finger in an elderly patient: CT and MRI
findings with pathologic correlation.
AB - Calcifying aponeurotic fibroma (CAF) is a rare, locally aggressive fibroblastic
lesion that occurs predominantly in the distal extremities of children and
adolescents. In the present study, a case of pathologically proven CAF arising in
the right little finger of a 69-year-old woman is presented. Physical examination
revealed a firm, immobile, non-tender mass. Plain radiographs showed a faintly
calcified soft tissue mass without bone involvement and computed tomography scans
clearly demonstrated the presence of the lesion. Magnetic resonance imaging
revealed that the lesion exhibited low to intermediate signal intensity on T1
weighted images and heterogeneous high signal intensity with small foci of low
signal intensity on T2-weighted spectral presaturation with inversion recovery
images. Contrast-enhanced fat-suppressed T1-weighted images demonstrated intense
heterogeneous enhancement throughout the mass. The patient underwent an
excisional biopsy. Histologically, the tumor showed a biphasic pattern, composed
of a moderately cellular fibromatosis-like component and irregular calcified
areas with polygonal epithelioid cells. There has been no evidence of local
recurrence four months following surgery. To the best of our knowledge, this case
report describes the oldest patient with this condition.
PMID- 25120612
TI - Promoter methylation of Raf kinase inhibitory protein: A significant prognostic
indicator for patients with gastric adenocarcinoma.
AB - DNA methylation has an important role in the development of carcinomas. As a
metastasis suppressor gene, Raf kinase inhibitory protein (RKIP) suppresses tumor
cell invasion and metastasis. In the present study, the associations between RKIP
protein expression and promoter methylation with clinicopathological parameters,
prognosis and survival rates in gastric adenocarcinoma were investigated. RKIP
protein expression and promoter methylation were measured in 135 cases of
surgically resected gastric adenocarcinoma specimens and corresponding normal
tissues using immunohistochemistry and methylation-specific polymerase chain
reaction, respectively. Kaplan-Meier analyses were performed to analyze the
patient survival rate. Prognostic factors were determined using multivariate Cox
analysis. RKIP promoter methylation was detected in 48.9% of gastric carcinoma
tissues and 5.17% of adjacent tissues (P<0.05). RKIP protein expression was
detected in 43.0% of gastric carcinoma tissues and 91.1% of adjacent tissues
(P<0.05). The protein expression levels and promoter methylation of RKIP were
shown to correlate with pathological staging, Union for International Cancer
Control-stage, tumor differentiation and lymph node metastasis (P<0.05). In
addition, the protein expression of RKIP in gastric carcinomas was demonstrated
to be associated with promoter methylation of RKIP. Survival analysis of gastric
carcinoma patients revealed that promoter methylation in RKIP-positive tumors
correlated with a significantly shorter survival time when compared with RKIP
negative tumors (P=0.0002, using the log-rank test). Using multivariate Cox
analysis, promoter methylation of RKIP was shown to be an independent prognostic
factor (P=0.033). These results indicated that abnormal promoter methylation of
RKIP may be one cause of downregulated RKIP expression. Downregulation of RKIP
expression was shown to correlate with the incidence and development of gastric
carcinomas. Thus, abnormal promoter methylation of RKIP may be a valuable
biomarker for estimating gastric carcinoma prognosis.
PMID- 25120613
TI - Lopinavir inhibits insulin signaling by promoting protein tyrosine phosphatase 1B
expression.
AB - Treatment with antiretroviral therapy, including protease inhibitors (PIs), may
result in metabolic side-effects, for example insulin resistance. The aim of the
present study was to investigate the mechanism of the dysregulation of insulin
signaling by two PIs, lopinavir and darunavir, by analyzing changes in the
expression or activity of proteins associated with insulin signaling. 3T3-L1
preadipocytes were pretreated with lopinavir or darunavir for 48 h and then
stimulated with insulin for 30 min. The cell lysates were subjected to western
blotting with anti-phospho-insulin receptor substrate (IRS) 1, anti-IRS1, anti
suppressor of cytokine signaling (SOCS) 1, anti-SOCS3 and anti-protein tyrosine
phosphatase (PTP) 1B antibodies and to immunoprecipitation with anti-IRS1
antibody. Translocation of glucose transporter 4 (GLUT4) following treatment with
lopinavir or darunavir was observed using immunofluorescence. While GLUT4 was
recruited to the cellular membrane in control adipocytes following insulin
stimulation, it was diffusely distributed in the cytosol in lopinavir-treated
adipocytes. In darunavir-treated adipocytes, GLUT4 was mainly recruited to the
cellular membrane, but some GLUT4 remained in the cytosol. After insulin
stimulation, IRS1 was tyrosine-phosphorylated to a greater extent in control
adipocytes compared with darunavir-treated adipocytes. Tyrosine phosphorylation
of IRS1 was inhibited in lopinavir-treated adipocytes. The expression of PTP1B
was upregulated in adipocytes pretreated with the PIs, particularly lopinavir,
compared with those pretreated with a vehicle control. The degree of regulation
in insulin signaling differs between lopinavir and darunavir. One mechanism by
which lopinavir regulates insulin signaling is by the promotion of PTP1B
expression.
PMID- 25120614
TI - Type 2 diabetes mellitus control and atherosclerosis prevention in a non-obese
rat model using duodenal-jejunal bypass.
AB - Type 2 diabetes mellitus (T2DM) is a prevalent disease worldwide and during its
conventional treatment, vascular complications remain unavoidable. Roux-en-Y
gastric bypass (GBP) is able to induce the remission of T2DM. However, studies of
duodenal-jejunal bypass (DJB), a modified procedure of GBP, are being carried out
to investigate its ability to induce the remission of T2DM and protect the aorta
from atherosclerosis. The present study aimed to investigate the effect of DJB on
the rate of T2DM remission and the prevention of atherosclerosis in the aorta in
rats with streptozotocin-induced diabetes without obesity, and to explore the
mechanism of DJB in protecting the aorta from atherosclerosis. A T2DM rat model
was established with a high-fat diet and low-dose streptozotocin. Surgery was
performed to analyze its effects on glucose homeostasis, lipid metabolism,
inflammation and pathological changes. Furthermore, changes in c-jun NH2-terminal
kinase 1 (JNK1) and inhibitor of kappaB kinase (IKKbeta) genes in the aorta
following DJB surgery were examined. Levels of blood glucose, lipids, insulin and
tumor necrosis factor (TNF)-alpha were significantly elevated in the T2DM
diabetic model compared with the non-diabetic control. A gradual recovery was
observed in the DJB group following surgery. Foam cells and atherosclerotic
plaques appeared in the ascending aortic tissue in the sham-surgery and T2DM
groups, whereas only slight lesions were observed in the DJB group. The
expression levels of JNK1 and IKKbeta genes in the aorta were significantly
increased in the sham-operated and T2DM groups compared with those in the DJB and
normal control groups. The present study demonstrated that DJB caused remission
of T2DM without weight loss in non-obese rats. Thus, DJB may delay or prevent the
occurrence and development of atherosclerosis in the aorta and this may occur
through the JNK1 and nuclear factor kappaB (NF-kappaB) signaling pathways.
PMID- 25120615
TI - Protective roles of erythropoiesis-stimulating proteins in chronic heart failure
with anemia.
AB - Anemia is a common comorbidity in patients with chronic heart failure (CHF) and
is frequently treated with erythropoiesis-stimulating proteins (ESPs). Previous
studies, however, have been relatively short in duration and have not provided
conclusive data on the safety or clinical efficacy of ESP treatment. The aim of
this study was to explore the safety and therapeutic effects of ESPs in patients
with anemia and CHF. A systematic literature search in EMBASE and MEDLINE from
their inception to July 2013 was performed, and clinical studies that evaluated
the effects of ESPs among patients with CHF were identified. Randomized clinical
trials comparing the effects of ESP treatment with those of placebo treatment or
usual care regimes in anemic patients with CHF were included. Nine randomized,
controlled trials were identified, comprising 750 patients with CHF and anemia
receiving ESP treatment for between three months and one year. ESP treatment had
a significantly lower risk of CHF hospitalization [relative risk (RR), 0.47; 95%
confidence interval (CI), 0.32-0.70; P=0.0002] and a moderate reduction in
mortality risk (RR, 0.68; 95% CI, 0.38-1.19; P=0.18). Treatment with ESPs in
patients with symptomatic CHF and anemia resulted in significant improvements in
hemoglobin, hematocrit and brain natriuretic peptide levels, as well as exercise
capacity, renal function, New York Heart Association class and left ventricular
ejection fraction. In conclusion, this study found that treatment with ESPs
exerts beneficial effects against CHF and is not associated with a higher
mortality rate or adverse effects. These outcomes support the instigation of a
trial evaluating the treatment of anemia with ESPs in patients with chronic CHF.
PMID- 25120616
TI - Toll-like receptor 4 monoclonal antibody attenuates lipopolysaccharide-induced
acute lung injury in mice.
AB - Toll-like receptor 4 (TLR4) has an important role in the recognition of
lipopolysaccharide (LPS) and in the activation of the inflammatory cascade. In
the present study, the effect of TLR4 monoclonal antibody (mAb) on LPS-induced
acute lung injury (ALI) was investigated in mice. A total of 45 male BALB/c mice
were randomly divided into three groups, namely, the control (group C), sepsis
(group S) and pretreatment groups (group P). Mice in group P were
intraperitoneally treated with TLR4 mAb 1 h prior to the intraperitoneal
administration of LPS. Following treatment with LPS for increasing times periods
in groups S and P, the mRNA expression level of TLR4 in the lung tissue and the
expression of inflammatory factors in the serum were analyzed by quantitative
polymerase chain reaction and enzyme-linked immunosorbent assays, respectively.
The degree of pulmonary edema, expressed as (wet weight - dry weight)/wet weight,
as well as the lung injury scores, observed using a light microscope, were also
analyzed. The results demonstrated that intraperitoneal administration of LPS in
mice increased the mRNA expression levels of TLR4, the secretion of inflammatory
factors in the serum, the degree of pulmonary edema and the lung injury score in
a time-dependent manner. However, pretreatment with TLR4 mAb effectively
attenuated the increased mRNA expression of TLR4 and the overproduction of
inflammatory factors to correct the pulmonary edema and the elevated lung injury
score induced by LPS. Therefore, TLR4 plays a critical role in LPS-induced ALI,
and the TLR4 mAb decreases the secretion of inflammatory factors and attenuates
the degree of pulmonary edema, thereby protecting the lungs from LPS-induced ALI.
PMID- 25120617
TI - Treatment protocols for growth hormone-secreting pituitary adenomas combined with
craniofacial fibrous dysplasia: A case report of atypical McCune-Albright
syndrome.
AB - McCune-Albright syndrome (MAS) is a rare, post-zygotic (non-germline) disorder,
characterized by hypersecretory endocrinopathies, fibrous dysplasia of the bone
and cafe-au-lait macules. The most common endocrine dysfunction is gonadal
hyperfunction; thus, hypersecretion of growth hormones (GHs) as a manifestation
of endocrine hyperfunction in MAS is rarely reported. MAS affects both genders,
although the majority of cases have been reported in young females. Atypical
presentations of MAS, with only one or two of the classic symptoms, have been
previously described, but remain particularly challenging due to the lack of a
diagnostic phenotype. In patients with atypical MAS, analysis of mutations in the
gene of the alpha-subunit of the stimulatory G-protein is limited; thus,
diagnosis is based on clinical judgment. In the present study, a male with
polyostotic fibrous dysplasia and GH-secreting pituitary adenomas, diagnosed with
atypical MAS, was reported. The pituitary adenoma was effectively treated with
radiotherapy and the patient underwent surgery for the polyostotic fibrous
dysplasia, with marked improvements observed in appearance.
PMID- 25120618
TI - Overexpression of netrin-1 increases the expression of tight junction-associated
proteins, claudin-5, occludin, and ZO-1, following traumatic brain injury in
rats.
AB - The function of the blood-brain barrier (BBB) depends on the integrity of tight
junction (TJ)-associated proteins. Netrin-1 is known to promote angiogenesis and
may also regulate the BBB. To understand the association between netrin-1 and the
TJ-associated proteins, the expression levels of proteins involved in maintaining
the integrity of the BBB, including netrin-1, claudin-5, occludin and zonula
occluden (ZO)-1, were investigated in the present study using quantitative
polymerase chain reaction, western blot analysis and immunofluorescence. The aim
of the present study was to determine the changes in BBB permeability and whether
pZsGreen1-N1 mediated overexpression of netrin-1 increased the expression of the
TJ-associated proteins following traumatic brain injury (TBI). The results
demonstrated that the levels of mRNA transcription and protein expression of the
TJ-associated proteins, claudin-5, occludin and ZO-1, were significantly reduced
following TBI. Furthermore, the changes in the expression of these three TJ
proteins were consistent with the changes in the BBB permeability, indicating
that weakening intercellular junctions leads to BBB opening. The present study
also demonstrated that netrin-1 significantly increased the downregulation of
claudin-5, occludin and ZO-1 expression levels induced by TBI, which provided a
basis for further investigation on the role of netrin-1 in the integrity of TJs
and proper functioning of the BBB.
PMID- 25120619
TI - Role of cystatin C in renal damage and the optimum cut-off point of renal damage
among patients with type 2 diabetes mellitus.
AB - The aims of the present study were to evaluate the roles of serum cystatin C
(SCysC) and urinary cystatin C (UCysC) in renal function impairment and
investigate the optimum cut-off point for renal function impairment among
patients with type 2 diabetes mellitus (DM). A total of 742 inpatients and
outpatients with type 2 DM (age, 20-75 years) were enrolled in this population
based cross-sectional study. The levels of SCysC and UCysC were determined and
the odds ratios (ORs) and 95% confidence interval (CIs) of the calculated risk
ratios of the different renal damage indicators were obtained. The levels of
UCysC, urinary beta2-microglobulin (Ubeta2-MG), urinary albumin (UALB) and SCysC
in the renal function impairment groups were observed in the following order: GFR
C>GFR-B>GFR-A (P<0.05 or P<0.01). According to the levels of GFR were divided
into 4 groups, group GFR-A >= 80ml/min, GFR-B group 50-80 ml/min, group Ccr-C 20
50 ml/min, group GFR-D <20 ml/min. Following adjustment for age and gender,
multivariate correlation analysis results revealed that levels of Ubeta2-MG,
UCysC and UALB negatively correlated with the glomerular filtration rate (GFR;
P<0.05 or P<0.01). In addition, the duration of DM and the levels of SCysC and
serum uric acid were shown to positively correlate with the GFR (P<0.05 or
P<0.01). ORs for early renal function impairment significantly increased from the
DM duration category of four years (OR, 1.74; 95% CI, 1.54-1.92). Receiver
operating characteristic analysis demonstrated that the optimum DM cut-off point
was four years, in which 60.79% sensitivity and 69.66% specificity were observed.
Therefore, UCsyC levels may be used as an efficient indicator for the evaluation
of early renal function impairment among patients with type 2 DM. In addition,
renal lesions may initially occur in the renal tubule and then form in the renal
glomerulus of patients with type 2 DM.
PMID- 25120620
TI - Irradiation facilitates the inhibitory effect of the heat shock protein 90
inhibitor NVP-BEP800 on the proliferation of malignant glioblastoma cells through
attenuation of the upregulation of heat shock protein 70.
AB - The present study aimed to investigate the effect of NVP-BEP800, a novel heat
shock protein (Hsp) 90 inhibitor of the 2-aminothieno[2,3-d]pyrimidine class, in
combination with radiation on glioblastoma cells. T98G human glioblastoma cells
were treated with dimethyl sulfoxide (DMSO), NVP-BEP800, NVP-BEP800 in
combination with X-ray irradiation (10 Gy, 20 min), or X-ray irradiation only,
and cultured for 40 h. Cell viability was measured upon completion of the
treatments. In addition, apoptosis was measured and immunoblot analysis was
performed to analyze the expression levels of cellular protein inhibitory kappaB
kinase beta (IKKbeta). The combined treatment with NVP-BEP800 and X-ray
irradiation resulted in the synergistic destruction of malignant cells.
Furthermore, NVP-BEP800 significantly induced apoptosis in the human glioblastoma
cells. The immunoblot analysis data indicated that NVP-BEP800 markedly reduced
the expression level of IKKbeta. The results also revealed that X-ray irradiation
significantly attenuated the increase in the level of Hsp70 in cells treated with
NVP-BEP800. Since elevated levels of Hsp70 are associated with drug resistance
induced by Hsp90 inhibitors, the effects of X-ray irradiation on Hsp70 levels may
be associated with the enhanced effect on cells of the presence of irradiation.
The results of the current study suggest that irradiation enhances the inhibitory
effect of NVP-BEP800 on the proliferation of malignant glioblastoma cells by
downregulating the expression level of cellular signaling protein IKKbeta and
attenuating the upregulation of Hsp70 that is induced by NVP-BEP800.
PMID- 25120621
TI - Effects of hypoxia-inducible factor-1alpha and matrix metalloproteinase-9 on
alveolar-capillary barrier disruption and lung edema in rat models of severe
acute pancreatitis-associated lung injury.
AB - The aim of this study was to investigate the effects of hypoxia-inducible factor
1alpha (HIF-1alpha) and matrix metalloproteinase-9 (MMP-9) on alveolar-capillary
barrier disruption and lung edema in rat models of severe acute pancreatitis
associated lung injury (PALI). A total of 40 male Sprague-Dawley rats were
randomly divided into a sham surgery group (n=10) and three PALI groups, in which
acute pancreatitis was induced by the retrograde infusion of 5% sodium
taurocholate (1 ml/kg). The PALI groups were as follows: i) Untreated PALI group
(n=10); ii) 2-methoxyestradiol (2ME2) group (5 mg/kg body mass; n=10); and iii)
2ME2 group (15 mg/kg body mass; n=10). In the two 2ME2 groups, the HIF-1alpha
inhibitor 2ME2 was administered intraperitoneally 1 h after the induction of AP.
The severity of the pancreatitis was evaluated by the serum amylase levels and
pathology. The severity of the lung injury was evaluated by the wet/dry ratio,
blood gas analysis and pathology. The alveolar-capillary barrier disruption was
assessed by Evans blue dye extravasation. The protein and mRNA expression levels
of HIF-1alpha and MMP-9 were studied using enzyme-linked immunosorbent assays
(ELISAs), western blot analysis and reverse transcription-polymerase chain
reaction. The active tumor necrosis factor-alpha levels were measured using an
ELISA. The HIF-1alpha inhibitor 2ME2 attenuated the severity of the pancreatitis
and PALI, while the lung edema and alveolar-capillary barrier disruption were
significantly ameliorated compared with those in the untreated PALI group.
Administration of the higher dose of 2ME2 significantly suppressed the protein
expression of MMP-9 in the lung tissues. The results indicate that HIF-1alpha has
a major function in alveolar-capillary barrier disruption and lung edema in PALI
via a molecular pathway cascade involving MMP-9. Inhibition of HIF-1alpha by 2ME2
attenuates alveolar-capillary barrier disruption and lung edema. Pharmacological
blockade of this pathway in patients with PALI may provide a novel therapeutic
strategy.
PMID- 25120623
TI - Inhibitory effect of gene combination in a mouse model of colon cancer with liver
metastasis.
AB - The aim of the present study was to establish an animal liver metastasis model
with human colon cancer and investigate the inhibitory effect of the wild type
(WT) p53 gene combined with thymidine kinase/ganciclovir (TK/GCV) and cytosine
deaminase/5-fluorocytosine (CD/5-FC) systems on liver metastasis of colon cancer.
A nude mouse liver metastasis model with human colon cancer was established via a
spleen cultivation method. A total of 32 nude mice were randomly divided into
four groups, each group with eight mice. Group 1 mice received splenic injections
of SW480 cells (control group), while group 2 mice were injected with SW480/p53
cells in the spleen. Group 3 mice were administered splenic injections of
SW480/TK-CD cells, and GCV and 5-FC were injected into the abdominal cavity.
Finally, group 4 mice received splenic injections of SW480/p53 cells mixed in
equal proportion with SW480/TK-CD cells, as well as GCV and 5-FC injections in
the abdominal cavity. These cells described were constructed in our laboratory
and other laboratories. The number of liver metastatic tumors, the liver
metastasis rate, conventional pathology, electron microscopy and other indicators
in the nude mice of each group were compared and observed. The nude mouse liver
metastasis model with human colon cancer was successfully established; the liver
metastasis rate of the control group was 100%. The results demonstrated that the
rate of liver metastasis in the nude mice in each treatment group decreased, as
well as the average number of liver metastatic tumors. Furthermore, the effect of
the treatment group with genetic combination (group 4) was the most effective,
demonstrating that WTp53 had a synergistic effect with TK/GCV and CD/5-FC.
Therefore, the present study successfully established a mouse model of liver
metastasis with colon cancer by injecting human colon cancer cells in the spleen.
Combined gene therapy was shown to have a synergistic effect, which effectively
inhibited the formation of liver metastasis from colon cancer.
PMID- 25120622
TI - Quantitative assessment of iron in heart and liver phantoms using dual-energy
computed tomography.
AB - The aim of the present study was to determine the correlation between dual-energy
computed tomography (DECT) Hounsfield units (HU) and iron concentration, as well
as the correlation between HU and magnetic resonance imaging (MRI)-derived R2*
values, in phantoms of the heart and liver tissue. Phantoms were constructed
containing pig heart or liver tissue and varying concentrations of iron (0.1, 5,
10, 15, 20 and 25 mg/ml). The phantoms were then examined by DECT and MRI. Linear
regression analysis was used to determine the correlations between HU and iron
concentration and HU and R2* values. The HU value of DECT increased with
increasing iron concentrations in the liver and heart phantoms in a linear
manner. The slope of the HU value change against iron concentration revealed that
DeltaH80-140 provided a better discernment of iron concentration as compared with
DeltaH100-140. The derived R2 values were all >0.9 for the associations of DECT
and MRI measurements with iron concentrations. Therefore, DECT may be used for
the determination of iron concentration in the liver and heart tissue, with the
results correlating with those obtained with MRI.
PMID- 25120624
TI - EBP50 regulates the apoptosis of pancreatic cancer cells by decreasing the
expression levels of Bcl-2.
AB - Increasing evidence has demonstrated that ezrin-radixin-moesin (ERM)-binding
phosphoprotein 50 (EBP50) is involved in the malignant transformation of numerous
human cancers. The present study investigated the involvement of EBP50
overexpression in the tumorigenicity of pancreatic cancer (PC). The results
revealed that overexpression of EBP50 suppressed cell growth, promoted cell
apoptosis and arrested G1-to-S phase progression in two human PC cell lines.
Overexpression of EBP50 also suppressed B-cell lymphoma 2 (Bcl-2) expression.
Furthermore, nude mouse tumor xenograft models were established by the
subcutaneous injection of cell lines stably transfected with an EBP50-expressing
plasmid. The in vivo data indicated that overexpression of EBP50 inhibited the
growth of the PC tumors and induced cell apoptosis. Thus, the present study
demonstrated that EBP50 overexpression induces growth inhibition and apoptosis in
PC by decreasing Bcl-2 expression. The results suggest that EBP50 may function as
a potential tumor suppressor in vivo and in vitro.
PMID- 25120625
TI - Gliomatosis cerebri mimicking acute viral encephalitis and with malignant
transformation of partial lesions: A case report.
AB - Gliomatosis cerebri (GC) is a rare glial neoplasm, characterized by extensive
diffuse brain infiltration and relative preservation of the underlying
architecture. In the present case report, a patient with type 2 GC, which
mimicked the clinicoradiological course of acute viral encephalitis, is
presented. A 56-year-old male presented with fever, dizziness, headache and
numbness in the right extremities three days prior to admission to hospital. The
cerebrospinal fluid (CSF) showed mild pleocytosis. Brain magnetic resonance
imaging (MRI) revealed hyperintensity on fluid-attenuated inversion recovery
images in the left frontal, temporal, insular lobes and in the left thalamus. No
signal enhancement was observed following gadolinium administration. The patient
was diagnosed with acute viral encephalitis of unknown cause and received a 10
day course of acyclovir, intravenously. At the follow-up three months later, the
patient had personality changes and memory deterioration. The results from the
follow-up MRI revealed no remarkable changes. At the follow-up six months after
presentation, the patient had expressive aphasia and severe headaches.
Subsequently, the patient had two tonic-clonic seizure onsets. The results from
the MRI showed an increase in lesion size, more edema around the lesion and
irregular enhancement in the left frontal lobe. However, the lesions in the left
temporal and insular lobes and in the left thalamus were nearly unchanged.
Magnetic resonance spectroscopy (MRS) showed elevated choline (Cho)/creatine (Cr)
and Cho/N-acetylaspartate (NAA) ratios, as well as decreased NAA/Cr ratios.
Surgery was performed and the neuropathological diagnosis of WHO grade III
astrocytoma was confirmed. Thus, it is important to pay attention to the
differential diagnoses of GC and acute viral encephalitis in patients who have
widespread MRI lesions. A brain biopsy is recommended for a diagnosis in this
case.
PMID- 25120626
TI - In vitro damage of Candida albicans biofilms by chitosan.
AB - With the increasing usage of indwelling medical devices in clinical practice, the
frequency of fungal infections has increased, such as that of Candida albicans
(C. albicans). Biofilms, a protected niche for microorganisms, are resistant to a
range of current antifungal agents. Chitosan is a polyatomic biopolymer with
advantageous biocompatibility, biodegradation, nontoxicity and antibacterial
properties. To investigate the inhibitory effect of chitosan on biofilms formed
by C. albicans, cell viability, 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H
tetrazolium-5-caboxanilide reduction, and morphological assays, including
fluorescence microscopy and scanning electron microscopy (SEM), were employed. As
assessed by cell viability assay, chitosan showed significant inhibitory effects
on the planktonic cells and the biofilm of C. albicans in a dose-dependent
manner. Fluorescence microscopy and SEM assays confirmed that the chitosan
treated group showed delayed C. albicans biofilm formation with defect
morphological features, due to the inhibitory effects of the vast majority of
fungal cell growth. In conclusion, C. albicans biofilms were compromised by the
treatment with chitosan, providing an alternative therapeutic strategy against
the fungal biofilms in the medical devices.
PMID- 25120627
TI - Cryopreserved mouse fetal liver stromal cells treated with mitomycin C are able
to support the growth of human embryonic stem cells.
AB - An immortalized mouse fetal liver stromal cell line, named KM3, has demonstrated
the potential to support the growth and maintenance of human embryonic stem cells
(hESCs). In this study, the characteristics of KM3 cells were examined following
cryopreservation at -70 degrees C and in liquid nitrogen for 15, 30 and 60 days
following treatment with 10 MUg/ml mitomycin C. In addition, whether the KM3
cells were suitable for use as feeder cells to support the growth of hESCs was
evaluated. The inhibition of mitosis without cell death was observed when the KM3
cells were treated with 10 MUg/ml mitomycin C for 2 h. The morphology of the KM3
cells cryopreserved in liquid nitrogen for 60 days was not markedly changed, and
the cell survival rate was 84.60+/-1.14%. By contrast, the survival rate of the
KM3 cells was 66.40+/-2.88% following cryopreservation at -70 degrees C for 60
days; the cells readily detached, were maintained for a shorter time, and had a
reduced expression level of basic fibroblast growth factor. hESCs cultured on KM3
cells cryopreserved in liquid nitrogen for 60 days showed the typical bird's nest
structure, with clear boundaries and a differentiation rate of 16.33+/-2.08%. The
differentiation rate of hESCs cultured on KM3 cells cryopreserved at -70 degrees
C for 60 days was 37.67+/-3.51%. These results indicate that the cryopreserved
KM3 cells treated with mitomycin C may be directly used in the subculture of
hESCs, and the effect is relatively good with -70 degrees C short-term or liquid
nitrogen cryopreservation.
PMID- 25120628
TI - Nicotinamide mononucleotide improves energy activity and survival rate in an in
vitro model of Parkinson's disease.
AB - Nicotinamide adenine dinucleotide (NAD+) repletion has been shown to provide
marked neuroprotection from genotoxic agent-induced neuronal and astrocyte cell
death. One of the key precursors of NAD+ is nicotinamide mononucleotide (NMN).
Therefore, it was hypothesized that NMN may attenuate apoptosis and improve
energy metabolism in Parkinson's disease (PD)-like behavioral and
neuropathological changes, and produce significant beneficial effects. In this
study, a cellular model of PD, using rotenone-treated PC12 cells, was established
to test the hypothesis that NMN may decrease PD-like pathological changes.
Experiments were carried out to investigate cell survival, including an
intracellular lactate dehydrogenase (LDH) assay. Apoptotic and necrotic cell
death, NAD+ levels and ATP levels were also evaluated. It was observed that NMN
was able to significantly attenuate the rotenone-induced reduction in the
survival rate of PC12 cells, as assessed by MTT and LDH assays. NMN treatment
also significantly reduced the rotenone-induced apoptosis of the cells, as
assessed by flow cytometry-based Annexin V/7-aminoactinomycin D staining.
Furthermore, NMN restored intracellular levels of NAD+ and ATP in the rotenone
treated cells, thus demonstrating the capacity of NMN to ameliorate mitochondrial
inhibitor-induced impairments of energy metabolism. The present study indicates
that NMN produces significant beneficial effects by attenuating apoptosis and
improving energy metabolism in a cellular model of PD. These results suggest that
NMN may become a promising therapeutic drug for PD.
PMID- 25120629
TI - Associations between apolipoprotein CIII concentrations and microalbuminuria in
type 2 diabetes.
AB - Microalbuminuria (MAU) is a strong predictor of diabetic nephropathy (DN), which
is the main cause of morbidity and mortality in patients with diabetes mellitus
(DM). Dyslipidemia exists in the majority of patients with DM and contributes to
micro- and macrovascular complications associated with DM. Apolipoprotein CIII
(apoCIII) is an inhibitor of the activity of lipoprotein lipase, which
metabolizes triglyceride (TG) in very low-density lipoprotein (VLDL) and
facilitates its clearance from plasma. The aim of the present study was to
investigate the associations between apoCIII and MAU and the effects of
atorvastatin in type 2 diabetes. In total, 120 subjects were divided into type 2
diabetes and type 2 DN groups, while 60 healthy subjects were selected as
controls. The patients with DN were administered 20 mg atorvastatin daily for 16
weeks. Blood pressure, body mass index (BMI) and levels of HbA1c, FBG, TG, VLDL
cholesterol (VLDL-C), apoCIII and MAU were markedly elevated in the type 2
diabetes and type 2 DN groups compared with those in the control group (P<0.01),
while high-density lipoprotein-cholesterol (HDL-C) levels were decreased
significantly (P<0.01). All patients with type 2 DN showed significantly elevated
blood pressure, apoCIII levels, MAU, course of the disease and rate of stroke and
retinopathy compared with the patients with type 2 diabetes (P<0.01). MAU was
significantly positively correlated with the course of the disease, systolic
blood pressure, diastolic blood pressure, BMI and HbA1c, FBG, TG, total
cholesterol, low-density lipoprotein-cholesterol, VLDL-C and apoCIII levels
(P<0.05), whereas negatively correlated with HDL-C levels (r=-0.194, P=0.020).
Logistic regression analysis showed that apoCIII levels were independently
associated with MAU (odds ratio, 1.100; 95% confidence interval, 1.037-1.153;
P<0.001). Atorvastatin improved the lipid profile and MAU in patients with type 2
DN (P<0.01). Therefore, the present study demonstrated that an independent
positive correlation exists between the levels of apoCIII and MAU in patients
with type 2 diabetes. Furthermore, atorvastatin may be used to improve the lipid
profile and MAU in type 2 DN.
PMID- 25120630
TI - Antiosteoporotic effects of Polycan in combination with calcium lactate-gluconate
in ovariectomized rats.
AB - The aim of the present study was to investigate the optimum composition of
Polycan (beta-glucan complex) and calcium lactate-gluconate (CaLG) that exhibited
the most beneficial effects in ovariectomy (OVX)-induced osteoporotic rats.
Polycan and CaLG single formulas (100 mg/kg each), and three doses (50, 100 and
200 mg/kg) of three mixed formulas [polycan:CaLG (PCLG)=1:99, 5:95 and 10:90]
were orally administered once a day for 84 days. The effects of the test
materials were compared with those of a risedronate sodium-treated group. OVX
resulted in an increase in body weight, decreased bone formation, elevated serum
osteocalcin levels and urine deoxypyridinoline/creatinine ratio, as well as
decreased serum bone-specific alkaline phosphatase levels, femur indices, bone
mineral content, bone mineral density and failure load. However, these OVX
induced osteoporotic changes markedly decreased following the administration of
the test materials. Continuous oral treatment of Polycan or CaLG single formulas
and the PCLG mixed formulas preserved bone mass and strength. The PCLG 10:90
mixed formula exhibited the most favorable synergistic antiosteoporotic effects
in the OVX-induced osteoporotic rats as compared with equal doses of the Polycan
or CaLG single formulas.
PMID- 25120631
TI - Naringin administration inhibits platelet aggregation and release by reducing
blood cholesterol levels and the cytosolic free calcium concentration in
hyperlipidemic rabbits.
AB - This study investigated the effects of naringin on platelet aggregation and
release in hyperlipidemic rabbits, and the underlying mechanisms. The safety of
naringin was also investigated. The rabbits were orally administered 60, 30 or 15
mg/kg of naringin once a day for 14 days after being fed a high fat/cholesterol
diet for four weeks. Following the two weeks of drug administration, the degree
of platelet aggregation induced by arachidonic acid, adenosine diphosphate and
collagen was significantly reduced by naringin at certain doses compared with
those in the rabbits of the model group (P<0.01). The levels of P-selectin and
platelet factor 4 (PF4) also decreased following treatment with naringin compared
with those of the model group. Certain doses of naringin significantly reduced
the total cholesterol (TC) levels and elevated the ratio of high-density
lipoprotein cholesterol to TC compared with those in the model group, and
significantly decreased the cytosolic free calcium concentration ([Ca2+]i). No
significant difference in the coagulation function was observed between the
control and drug-treatment groups. These results indicate that naringin improved
platelet aggregation and inhibited the excessive release of P-selectin and PF4 in
hyperlipidemic rabbits. This study suggests that the antiplatelet effect of
naringin may be due to its ability to regulate the levels of blood cholesterol
and [Ca2+]i in platelets. Naringin also did not cause bleeding in the
hyperlipidemic rabbits.
PMID- 25120632
TI - Pharmacological postconditioning with tanshinone IIA attenuates myocardial
ischemia-reperfusion injury in rats by activating the phosphatidylinositol 3
kinase pathway.
AB - Tanshinone IIA, one of the active ingredients in the Chinese medicine Danshen, is
cardioprotective when applied prior to sustained myocardial ischemia. The present
study aimed to investigate whether pharmacological postconditioning with
tanshinone IIA attenuates myocardial ischemia-reperfusion injury when applied
prior to prolonged reperfusion following a sustained ischemia. A total of 88
Sprague-Dawley rats received 30 min myocardial ischemia followed by 5 or 120 min
reperfusion. Compared with the ischemia-reperfusion model group, the group that
received an intravenous injection of 10 mg/kg tanshinone IIA prior to reperfusion
had a reduced myocardial infarct size, higher levels of phospho-Akt and phospho
endothelial nitric oxide synthase and less reduction in the optical density of
the mitochondria at 540 nm, indicating that the mitochondrial permeability
transition (MPT) was attenuated. The cardioprotective effect conferred by
tanshinone IIA was abolished by LY294002, a specific inhibitor of
phosphatidylinositol 3-kinase (PI3K). These results demonstrate that tanshinone
IIA postconditioning protects the myocardium from ischemia-reperfusion injury
through the PI3K/Akt pathway, and the MPT may be also involved in this process.
PMID- 25120633
TI - Effects of spironolactone and losartan on the early neovascularization of acute
myocardial infarction.
AB - The aim of the present study was to investigate the effects of spironolactone and
losartan on the early healing stage of acute myocardial infarction (AMI) in rats.
An AMI rat model was established and the rats were randomly divided into four
groups: AMI (n=12), AMI + spironolactone (AMI + S; n=12), AMI + losartan (AMI +
L; n=12) and AMI + spironolactone combined with losartan (AMI + S + L; n=12).
Sham-operated rats served as a control group (n=12). The expression levels of
matrix metalloproteinases (MMPs) and tissue inhibitors of matrix
metalloproteinases (TIMPs) in the non-infarcted myocardium surrounding the AMI
area were determined using immunohistochemistry. In addition, the capillary
density in the non-infarcted myocardium surrounding the AMI area was detected.
The capillary densities around the infarcted area in the AMI and treatment groups
at day 7 and 14 following AMI surgery were significantly higher compared with the
sham-operated rats. Compared with the AMI group, the capillary densities around
the infarcted area and the ratio of MMPs/TIMP-1 were increased in the treatment
groups following AMI surgery; however, the increased ratio of MMPs/TIMP-1 was
reduced at day 14 following AMI surgery. Therefore, these results indicated that
spironolactone and losartan may promote the formation of collateral circulation
in the non-infarcted tissue surrounding the infarcted area by regulating the
production of MMPs.
PMID- 25120635
TI - Autologous stem cell transplantation for a monoclonal gammopathy of undetermined
significance mimicking amyotrophic lateral sclerosis: A case report.
AB - It is rare for patients with monoclonal gammopathy of undetermined significance
(MGUS) to present with clinical features of fatal motor neuron disease, for
example amyotrophic lateral sclerosis (ALS). There is no standard and effective
therapy for either MGUS or ALS. In addition, stem cell transplantation appears to
be ineffective for the treatment of this disease. In the present study, a 47-year
old female with MGUS that mimicked ALS is presented. The M-protein levels of the
patient were normalized following two cycles of chemotherapy and autologous stem
cell transplantation treatment. MGUS was found to be alleviated and the symptoms
of ALS did not deteriorate. The results showed a positive therapeutic effect of
autologous stem cell transplantation for MGUS.
PMID- 25120634
TI - Effect of sodium ferulate on delayed rectifier K+ currents in PC12 cells.
AB - In order to investigate the effect of sodium ferulate (SF) on voltage-activated
K+ channels, the delayed rectifier K+ current (Ik) in PC12 rat pheochromocytoma
cells was recorded using the automated patch-clamp method. The results indicated
that following the application of SF, the Ik in PC12 cells was significantly
decreased in a concentration-dependent manner. The analysis of activation kinetic
curves and inactivation kinetic curves of Ik showed that SF had an effect on the
activation and inactivation kinetics. Following the application of 15.3 MUM SF,
the activation curve of the Ik of PC12 cells was shifted to positive potentials
and the inactivation curve of the Ik of PC12 cells was shifted to negative
potentials. This study revealed that the delayed rectifier K+ currents of PC12
cells were inhibited following SF treatment in a concentration-dependent manner.
The mechanism may be associated with the delayed activation and enhanced
inactivation of Ik-associated channels.
PMID- 25120636
TI - Exposure to high levels of glucose increases the expression levels of genes
involved in cholesterol biosynthesis in rat islets.
AB - Cells continually adjust their gene expression profiles in order to adapt to the
availability of nutrients. Glucose is a major regulator of pxancreatic beta-cell
function and cell growth. However, the mechanism of beta-cell adaptation to high
levels of glucose remains uncertain. To identify the specific targets responsible
for adaptation to high levels of glucose, the differentially expressed genes from
primary rat islets treated with 3.3 and 16.7 mmol/l glucose for 24 h were
detected by DNA microarray. The results revealed that the expression levels of
genes that encode enzymes required for de novo cholesterol biosynthesis [3
hydroxy-3-methylglutaryl-CoA synthase 1 (Hmgcs1), 3-hydroxy-3-methylglutaryl-CoA
reductase (Hmgcr), mevalonate (diphospho) decarboxylase (Mvd), isopentenyl
diphosphate delta-isomerase 1 (Idi1), squalene epoxidase (Sqle) and 7
dehydrocholesterol reductase (Dhcr7)] were significantly increased in islets
treated with high levels of glucose compared with those in the islets treated
with lower glucose levels. Quantitative polymerase chain reaction further
confirmed that glucose stimulated the expression levels of these genes in a dose-
and time-dependent manner. A similar result was obtained in islets isolated from
rats subjected to 12, 24, 48 and 72 h of continuous glucose infusion. It has
previously been recognized that cholesterol homeostasis is important for beta
cell function. The present study provides, to the best of our knowledge, the
first evidence for the involvement of the de novo cholesterol biosynthesis
pathway in the adaptation of rat islets to high levels of glucose in vitro and in
vivo.
PMID- 25120637
TI - Protective effects of Guanxin Shutong capsule drug-containing serum on tumor
necrosis factor-alpha-induced endothelial dysfunction through nicotinamide
adenine dinucleotide phosphate oxidase and the nitric oxide pathway.
AB - The Chinese medicinal formula Guanxin Shutong capsule (GXSTC) has been used for
almost 10 years as a clinical treatment for chest pain, depression, palpitation
and cardiovascular diseases. The aim of this study was to investigate the effects
of GXSTC drug-containing serum on tumor necrosis factor-alpha (TNF-alpha)
stimulated endothelial cells. Cell viability was measured by MTT assay, and
nitric oxide (NO) levels and NO synthase (NOS) activity were measured as
standards of endothelial dysfunction. Malondialdehyde (MDA) levels and superoxide
dismutase (SOD) activity were evaluated using commercial kits. In addition, the
protein expression of endothelial NOS (eNOS), AKT and nicotinamide adenine
dinucleotide phosphate (NADPH) oxidase subunits was examined to evaluate the
effect of GXSTC drug-containing serum on ECV304 cells. GXSTC significantly
reversed the decrease in NO production induced by TNF-alpha (5 ng/ml) in ECV304
cells. The expression of NADPH oxidase subunits was increased by TNF-alpha
treatment, but markedly inhibited by treatment with GXSTC in TNF-alpha-stimulated
cells. In summary, GXSTC increased the production of NO in ECV304 cells and
exerted a protective effect on ECV304 cells stimulated with TNF-alpha by
upregulating the mRNA and protein expression of eNOS. This was accompanied by
increased SOD activity and reduced MDA levels. These results suggested that GXSTC
protects the endothelium via the NO pathway and exhibits antioxidant effects.
PMID- 25120638
TI - Inhibition of Aurora-B suppresses HepG2 cell invasion and migration via the
PI3K/Akt/NF-kappaB signaling pathway in vitro.
AB - In the present study, the effect of Aurora-B inhibition on HepG2 cell invasion
and migration in vitro was investigated. A recombinant plasmid targeting the
Aurora-B gene (MiR-Aurora-B) was used to inhibit Aurora-B expression in HepG2
cells. Cell migration and invasion were investigated using Transwell migration
and invasion assays. The results demonstrated that cell invasion and migration
were suppressed by inhibiting Aurora-B. In addition, the effect of Aurora-B
inhibition on the activity of the phosphoinositide 3-kinase (PI3K)/Akt/nuclear
factor (NF)-kappaB signaling pathway was investigated by analyzing the protein
expression levels of phosphorylated (p)-Akt, Akt, NF-kappaB p65, matrix
metalloproteinase (MMP)-2 and MMP-9 using western blot analysis. The results
demonstrated that the protein expression levels of p-Akt, NF-kappaB p65, MMP-2
and MMP-9 were reduced significantly by inhibiting Aurora-B. Therefore,
inhibition of Aurora-B was shown to suppress hepatocellular carcinoma cell
migration and invasion by decreasing the activity of the PI3K/Akt/NF-kappaB
signaling pathway in vitro.
PMID- 25120639
TI - Progesterone protects blood-brain barrier function and improves neurological
outcome following traumatic brain injury in rats.
AB - Inflammatory responses are associated with blood-brain barrier (BBB) dysfunction
and neurological deficits following traumatic brain injury (TBI). The aim of the
present study was to investigate the effects of progesterone on the expression of
the inflammatory mediators prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2),
nuclear factor kappaB (NF-kappaB) and tumor necrosis factor-alpha (TNF-alpha) in
the brain, BBB permeability, cerebral edema and neurological outcome, as well as
to explore the mechanism of its neuroprotective effect. In this study, male rats
were randomly divided into three groups: a sham-operated group (SHAM), a TBI
group (TBI) and a progesterone treatment group (TBI-PROG). The TBI model was
established using a modified Feeney's weight-dropping method. Brain samples were
extracted 24 h following injury. The expression levels of COX-2 and NF-kappaB
were examined using immunohistochemistry, whilst the expression levels of PGE2
and TNF-alpha were detected by enzyme-linked immunosorbent assay. BBB
permeability was analyzed using Evans blue and cerebral edema was determined
using the dry-wet method. The neurological outcome was evaluated using the
modified neurological severity score test. The results revealed that progesterone
treatment significantly reduced post-injury inflammatory response, brain edema
and Evans blue dye extravasation, and improved neurological scores compared with
those in the TBI group. In conclusion, the inhibition of inflammation may be an
important mechanism by which progesterone protects the BBB and improves
neurological outcome.
PMID- 25120640
TI - Dendrobium candidum Wall. ex Lindl. attenuates CCl4-induced hepatic damage in
imprinting control region mice.
AB - The aim of the present study was to determine the preventive effect of the
traditional Chinese medicine, Dendrobium candidum Wall ex Lindl. (D. candidum),
on CCl4-induced hepatic damage in mice. The CCl4-induced hepatic damage mice were
treated with D. candidum, and the serum levels of aspartate aminotransferase
(AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), triglyceride
(TG) and total cholesterol (TC) were determined. In addition, serum cytokine
levels of interleukin (IL)-6, IL-12, tumor necrosis factor (TNF)-alpha and
interferon (IFN)-gamma were analyzed with kits, while liver tissues were analyzed
using hematoxylin and eosin staining and reverse transcription polymerase chain
reaction (RT-PCR). Furthermore, the contents of D. candidum were determined by
nuclear magnetic resonance (NMR). D. candidum was demonstrated to successfully
prevent hepatic damage in mice. The serum levels of AST, ALT and LDH were
significantly decreased when the mice were treated with 200 and 400 mg/kg D.
candidum, as compared with the control mice (P<0.05). The lowest enzymatic
activities were exhibited in the 400 mg/kg D. candidum group, which produced
similar results to the positive control drug, silymarin. In addition, in the 400
mg/kg D. candidum group, the highest levels of TG and TC were observed among the
treated groups. D. candidum-treated groups also demonstrated reduced levels of
the serum proinflammatory cytokines, IL-6, IL-12, TNF-alpha and IFN-gamma. The
sections of liver tissue examined during histopathology in the high concentration
400 mg/kg D. candidum group recovered well from CCl4 damage; however, the
sections in the 200 mg/kg D. candidum group revealed necrosis to a more serious
degree. RT-PCR analysis was conducted on inflammation-associated genes, including
nuclear factor (NF)-kappaB, IkappaB-alpha, inducible nitric oxide synthase (iNOS)
and cyclooxygenase (COX)-2, in the livers of the mice. The 400 mg/kg D. candidum
group demonstrated significantly decreased mRNA expression levels of NF-kappaB,
iNOS and COX-2, but an increased expression level of IkappaB-alpha when compared
with the CCl4-treated control group. Furthermore, using NMR, 11 compounds were
identified in the D. candidum leaf, whose functional contents may aid the
preventive effect observed in the current study. Therefore, D. candidum may
potentially contribute to the prevention of CCl4-induced hepatic damage in vivo.
PMID- 25120641
TI - NUP214 fusion genes in acute leukemia (Review).
AB - Nucleoporin 214 (NUP214), previously termed CAN, is required for cell cycle and
nucleocytoplasmic transport. The genetic features and clinical implications of
five NUP214-associated fusion genes are described in this review. SET-NUP214 was
most frequently observed in T-cell acute lymphoblastic leukemia (T-ALL),
concomitant with the elevated expression of HOXA cluster genes. Furthermore, the
fusion transcript may be regarded as a potential minimal residual disease marker
for SET-NUP214-positive patients. Episomal amplifications of NUP214-ABL1 are
specific to T-ALL patients. The NUP214-ABL1 gene is observed in ~6% of T-ALL, in
children and adults. Targeted tyrosine kinase inhibitors plus standard
chemotherapy appear to present a promising treatment strategy. DEK-NUP214 is
formed by the fusion of exon 2 of DEK and exon 6 of NUP214. Achieving molecular
negativity of DEK-NUP214 is of great importance for individual management. SQSTM1
NUP214 and NUP214-XKR3 were only identified in one T-ALL patient and one cell
line, respectively. The NUP214 fusions have significant diagnostic and
therapeutic implications for leukemia patients. Additional NUP214-associated
fusions require identification in future studies.
PMID- 25120642
TI - Aberrant DNA methylation in hepatocellular carcinoma tumor suppression (Review).
AB - Aberrant DNA methylation leads to altered gene expression, resulting in cancerous
features. Numerous tumor suppressor genes are silenced by DNA methylation during
hepatocarcinogenesis. Promoter CpG island hypermethylation is an important
mechanism for inactivating tumor suppressor genes in hepatocellular carcinoma
(HCC). Hypermethylation of CpG islands in the p16 (INK4a) and p15 (INK4b)
promoters may increase the risk of developing HCC, particularly hepatitis B virus
related HCC. Environmental factors can lead to geographic variations in the
methylation status of CpG islands. Aberrant DNA methylation of CpG islands is
catalyzed by DNA methyltransferases (DNMTs). Thus, abnormal variations of DNMTs
can contribute to hepatocarcinogenesis. In hepatitis-related HCC, microRNAs
participate in hepatocarcinogenesis by directly targeting DNMTs, during which
hepatitis B virus X acts as a regulator. DNA methylation may also contribute to
HCC tumorigenesis by regulating the cell cycle. Based on the importance of DNA
methylation in tumor suppression of HCC, certain DNA methylations may predict the
risk of tumor development, tumor staging, patient survival and HCC recurrence.
PMID- 25120643
TI - Potential new role of the GHSR-1a-mediated signaling pathway in cardiac
remodeling after myocardial infarction (Review).
AB - The gastrointestinal hormone ghrelin has important cardiovascular protective
effects, however, its specific mechanisms are not yet completely understood.
Recent studies have shown that the ghrelin receptor, growth hormone secretagogue
receptor type 1a (GHSR-1a), regulates cell proliferation, apoptosis and
inflammation-related signaling pathways. In human aortic endothelial cells,
ghrelin activates NO production through AMP-activated protein kinase (AMPK) and
Akt activation, and these effects can be blocked by knockdown of GHSR-1a. Obese
mice have been found to exhibit an increased GHSR-1a content and expression in
the heart, associated with an increase in phosphatidylinositol 3-kinase (PI3K)
content and an increase AKT content and phosphorylation. Furthermore, GHSR-1a
expression was observed to be increased in heart failure after myocardial
infarction (MI) in rats. Given such complexity in GHSR-1a signaling and crosstalk
with the AMPK and PI3K/Akt signaling pathways, both of which are well-known
factors involved in cardiac remodeling after MI, we speculate that GHSR-1a
signaling may play a regulatory role in cardiac protection and hope to identify
new drugs targets. However, to date, no direct association between GHSR-1a and
cardiac remodeling has been found. Therefore, further studies are required.
PMID- 25120644
TI - Normal tissue studies in radiation oncology: A systematic review of highly cited
articles and citation patterns.
AB - Radiation therapy is one of the cornerstones of modern multidisciplinary cancer
treatment. Normal tissue tolerance is critical as radiation-induced side effects
may compromise organ function and quality of life. The importance of normal
tissue research is reflected by the large number of scientific articles, which
have been published between 2006 and 2010. The present study identified important
areas of research as well as seminal publications. The article citation rate is
among the potential indicators of scientific impact. Highly cited articles,
arbitrarily defined as those with >=15 citations, were identified via a
systematic search of the citation database, Scopus. Up to 608 articles per year
were published between 2006 and 2010, however, <10% of publications in each year
accumulated >=15 citations. This figure is notably low, when compared with other
oncology studies. A large variety of preclinical and clinical topics, including
toxicity prediction, the dose-volume relationship and radioprotectors,
accumulated >=15 citations. However, clinical prevention or mitigation studies
were underrepresented. The following conclusion may be drawn from the present
study; despite the improved technology that has resulted in superior dose
distribution, clinical prevention or mitigation studies are critical and must
receive higher priority, funding and attention.
PMID- 25120645
TI - Colorectal laterally spreading tumors show characteristic expression of cell
polarity factors, including atypical protein kinase C lambda/iota, E-cadherin,
beta-catenin and basement membrane component.
AB - Colorectal flat-type tumors include laterally spreading tumors (LSTs) and flat
depressed-type tumors. The former of which shows a predominant lateral spreading
growth rather than an invasive growth. The present study examined the
morphological characteristics of LSTs, in comparison with polypoid- or flat
depressed-type tumors, along with the expression of atypical protein kinase C
(aPKC) lambda/iota, a pivotal cell polarity regulator, and the hallmarks of cell
polarity, as well as with type IV collagen, beta-catenin and E-cadherin. In
total, 37 flat-type (24 LSTs and 13 flat depressed-type tumors) and 20 polypoid
type colorectal tumors were examined. The LSTs were classified as 15 LST adenoma
(LST-A) and nine LST cancer in adenoma (LST-CA). An immunohistochemical
examination was performed on aPKC lambda/iota, type IV collagen, beta-catenin and
E-cadherin. The LST-A and -CA showed a superficial replacing growth pattern, with
expression of beta-catenin and E-cadherin in the basolateral membrane and type IV
collagen along the basement membrane. In addition, 86.6% of LST-A and 55.6% of
LST-CA showed aPKC lambda/iota expression of 1+ (weak to normal intensity
staining in the cytoplasm compared with the normal epithelium). Furthermore, ~45%
of the polypoid-type adenomas showed 2+ (moderate intensity staining in the
cytoplasm and/or nucleus) and 66.7% of the polypoid-type cancer in adenoma were
3+ (strong intensity staining in the cytoplasm and nucleus). A statistically
significant positive correlation was observed between the expression of aPKC
lambda/iota and beta-catenin (r=0.842; P<0.001), or type IV collagen (r=0.823;
P<0.001). The LSTs showed a unique growth pattern, different from the expanding
growth pattern presented by a polypoid tumor and invasive cancer. The growth
characteristics of LST appear to be caused by adequate coexpression of beta
catenin, type IV collagen and aPKC lambda/iota.
PMID- 25120647
TI - Matrigel induces L-plastin expression and promotes L-plastin-dependent invasion
in human cholangiocarcinoma cells.
AB - The function of the extracellular matrix (ECM) in the tumor microenvironment is
not limited to forming a barrier against tumor invasion. As demonstrated in
pathological specimens, cholangiocarcinoma samples exhibit an enrichment of the
ECM surrounding the tumor cells. In this study, we examined involvement of the
ECM in the regulation of the invasiveness of cholangiocarcinoma cells. The RMCCA1
cholangiocarcinoma cell line was cultured in culture plates either with or
without a coating of reconstituted ECM basement membrane preparation (BD Matrigel
matrix). In vitro invasion assays were then performed. In addition, the protein
expression profile of the cell line was examined using two-dimensional gel
electrophoresis and liquid chromatography-tandem mass spectrometry. The proteins
expressed and their functional associations with cancer progression were
determined. Culturing the RMCCA1 cell line in the BD Matrigel matrix induced cell
invasion. Numerous proteins were induced by culturing the RMCCA1 cells in the
matrix gel. The expression of L-plastin, an actin-binding protein, was
significantly upregulated. The knockdown of L-plastin expression by siRNA
silencing significantly suppressed the cellular response to matrix gel-stimulated
cancer cell invasion. The ECM promotes the invasiveness of cholangiocarcinoma
cells by upregulating L-plastin. These findings suggest the potential
exploitation of this mechanism as a means of inhibiting the invasiveness of
cholangiocarcinoma cells.
PMID- 25120646
TI - Immunohistochemical expression of four different stem cell markers in prostate
cancer: High expression of NANOG in conjunction with hypoxia-inducible factor
1alpha expression is involved in prostate epithelial malignancy.
AB - Cancer stem cells (CSCs) have been identified in a variety of cancer types,
including prostate cancer. The aim of the present study was to evaluate the
immunohistochemical expression of NANOG, octamer 4 (OCT4), cluster of
differentiation 133 (CD133) and NESTIN, which are all CSC markers, and assess
their function in prostate carcinogenesis. A total of 114 patients were referred
to the Kanazawa Medical University Hospital (Uchinada, Japan) having presented
with elevated serum prostate-specific antigen levels and/or abnormal digital
rectal examinations, and underwent transrectal ultrasound sonography guided eight
core biopsies. The prostate pathological specimens were re-evaluated for
selection in this study. When specimens were diagnosed as prostate cancer,
immunohistochemical analysis of the four different stem cell markers (NANOG,
OCT4, CD133 and NESTIN) and hypoxia-inducible factor (HIF)-1alpha was performed.
Prostate cancer was found in 38 cases (33.3%), while the other patients had
benign prostate hyperplasia with prostatitis. All prostate cancers were
histopathologically identified as adenocarcinomas of various grades, and cancer
cells and intraepithelial neoplasia (high grade) were immunohistochemically shown
to express NANOG and OCT4, but not CD133 and NESTIN. The intensity of NANOG
expression was much greater than that of OCT4, and the positivity and intensity
of the four stem cell markers, including NANOG, were elevated with high Gleason
scores. A significant correlation was observed between the NANOG- and HIF-1alpha
positive regions. The CSC markers, in particular OCT4 and NANOG, were
immunohistochemically expressed in prostate cancers. Furthermore, HIF-1alpha
expression may affect NANOG and/or OCT4 expression. The findings of the current
study suggested that NANOG expression may be a biomarker for the diagnosis of
prostate cancer, and the coexpression of NANOG and HIF-1alpha may be involved in
prostate carcinogenesis.
PMID- 25120648
TI - Coexistence of t(15;17) and t(15;16;17) detected by fluorescence in situ
hybridization in a patient with acute promyelocytic leukemia: A case report and
literature review.
AB - Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21),
which results in the fusion of the promyelocytic leukemia (PML) gene at 15q22
with the retinoic acid alpha-receptor (RARA) gene at 17q21. The current study
presents the case of a 54-year-old female with APL carrying the atypical PML/RARA
fusion signal due to a novel complex variant translocation
t(15;16;17)(q22;q24;q21), as well as the classical PML/RARA fusion signal.
Subsequent array comparative genomic hybridization revealed somatic, cryptic
deletions on 3p25.3, 8q23.1 and 12p13.2-p13.1, and a duplication on 8q11.2;
however, no genetic material loss or gain was observed in the breakpoint regions
of chromosomes 15, 16 or 17. To the best of our knowledge, this is the first
report of the coexistence of two abnormal clones, one classical and one variant,
presenting simultaneously in addition to cryptic chromosome segmental imbalances
in an adult APL patient.
PMID- 25120649
TI - Telomerase Cajal body protein 1 depletion inhibits telomerase trafficking to
telomeres and induces G1 cell cycle arrest in A549 cells.
AB - Telomerase Cajal body protein 1 (TCAB1) is a telomerase holoenzyme, which is
markedly enriched in Cajal bodies (CBs) and facilitates the recruitment of
telomerase to CBs in the S phase of the cell cycle. This recruitment is dependent
on TCAB1 binding to a telomerase RNA component. The majority of cancer cells are
able to grow indefinitely due to telomerase and its mechanism of trafficking to
telomeres. In the present study, a certain level of TCAB1 expression in A549
human lung cells was identified and TCAB1 knockdown exhibited a potent
antiproliferative effect on these cells, which was coupled with a decrease in the
cell density and activity of the cellular enzymes. In addition, TCAB1-depletion
was demonstrated to inhibit telomerase trafficking to telomeres in the A549
cells, leading to subsequent G1 cell cycle arrest without inducing apoptotic cell
death. Overall, these observations indicated that TCAB1 may be essential for A549
cell proliferation and cell cycle regulation, and may be a potential candidate
for the development of a therapeutic target for lung adenocarcinomas.
PMID- 25120650
TI - Clinical significance of the 'not otherwise specified' subtype in candidates for
resectable non-small cell lung cancer.
AB - The histological subtype of non-small-cell lung cancer (NSCLC) is a significant
factor when selecting treatment strategies. However, cases are occasionally
encountered that are diagnosed as 'not otherwise specified' (NOS) prior to
surgery, due to an uncertain histological subtype. The present study investigated
the prognostic significance of the NOS subtype for patients with resectable
NSCLC. Between 2001 and 2011, 1,913 patients were diagnosed with NSCLC using
transbronchial biopsy and underwent surgical resection at two facilities in
Japan. Of these patients, 151 (7.9%) were pre-operatively diagnosed with NSCLC
NOS (NOS group) and the remainder had confirmed histological subtypes (confirmed
group). The present study compared the clinicopathological features and prognoses
of these groups. Analyses of resected specimens revealed that pleomorphic cell
carcinoma, large cell neuroendocrine cell carcinoma, large cell carcinoma and
adenosquamous carcinoma were significantly more common in the NOS group than in
the confirmed group (P<0.001, P=0.002, P=0.019 and P=0.014, respectively). The
five-year survival rate was significantly poorer in the NOS group (60.5 vs.
67.1%; P=0.010), particularly for stage I disease (70.8 vs. 80.7%; P=0.007). The
results of a multivariate analysis of overall survival indicated that NOS was a
significant independent prognostic factor (hazard ratio, 1.40; 95% confidence
interval, 1.02-1.86; P=0.041). These results indicated that pre-operative NOS was
significantly associated with poorer survival, including for stage I disease. In
conjunction with other clinicopathological parameters, NOS can be a useful
prognostic factor when deciding on a treatment strategy for NSCLC.
PMID- 25120651
TI - Aberrant methylation and silencing of IRF8 expression in non-small cell lung
cancer.
AB - The aim of the present study was to investigate the aberrant methylation and
altered expression of the interferon regulatory factor 8 (IRF8) gene in non-small
cell lung cancer (NSCLC). Pyrosequencing assays were performed on 191 tumor
specimens from NSCLC patients. The changes in IRF8 mRNA expression, prior to and
following treatment with a demethylating agent and methylation itself, were
examined in 13 lung cancer cell lines by quantitative polymerase chain reaction
(qPCR) and pyrosequencing. IRF8 protein expression was examined in 94 of the 191
NSCLC specimens by immunohistochemical analysis. The IRF8 methylation level was
significantly higher in the tumor tissues than in matched non-malignant lung
tissues (P<0.0001). IRF8 was more frequently methylated in tumor tissues compared
with matched non-malignant lung tissues, as defined by a predetermined cut-off
value (P<0.0001). The IRF8 methylation level was strongly correlated with the
change in mRNA expression in lung cancer cell lines and with the protein
expression level in primary tumors. The IRF8 gene was more frequently methylated
in patients without an epidermal growth factor receptor (EGFR) mutation than in
patients with an EGFR mutation (P=0.015). IRF8 methylation correlated with
recurrent prognosis in adenocarcinomas (log-rank test, P=0.048). IRF8 protein
expression was frequently silenced in males, smokers, patients with non
adenocarcinoma or with wild-type EGFR, or in an advanced stage. IRF8 is often
silenced by its methylation, which is a frequent event in NSCLC and, therefore,
methylation of IRF8 may act as a prognostic marker for recurrence. Analysis of
IRF8 methylation status may provide novel opportunities for improved prognosis
and therapy of resected NSCLC.
PMID- 25120652
TI - Long-term urodynamic evaluation of laparoscopic radical cystectomy with
orthotopic ileal neobladder for bladder cancer.
AB - The long-term urodynamics of laparoscopic radical cystectomy with orthotopic
ileal neobladder for bladder cancer remain unclear in the clinical setting. The
present prospective observational study was conducted between January 2010 and
December 2012 to evaluate the 6-month and 12-month follow-up data of urodynamic
changes of bladder cancer patients who were initially treated by laparoscopic
radical cystectomy with orthotopic ileal neobladder. A total of 53 eligible
patients were included, and all patients were followed up for at least 12 months,
with a median time of 18 months. During the follow-up period, no patients
reported difficulty urinating, and the daily frequency of urination and the urine
output were gradually improved with time. Dynamic urodynamic examinations showed
that the maximum flow rate (11.4+/-1.1 vs. 7.3+/-1.4 ml/sec; P<0.001), residual
urine content (22.8+/-10.5 vs. 40.7+/-12.7 ml; P<0.001), maximum bladder capacity
(373.8+/-62.2 vs. 229.7+/-56.3 ml; P<0.001) and maximum bladder pressure during
filling (35.8+/-6.7 vs. 26.4+/-7.0 cm H2O; P<0.001) at 12 months were all
improved significantly compared with that at 6 months after the initial surgical
treatment. However, there were no significant differences in maximum bladder
pressure during voiding (75.7+/-24.7 vs. 73.1+/-24.7 cm H2O; P=0.618) and bladder
compliance (26.9+/-13 vs. 27.4+/-13.1 cm H2O; P=0.848) at 12 and 6 months after
initial surgical treatment. In conclusion, the urodynamics of this orthotopic
ileal neobladder gradually improve, and its long-term urine storage and voiding
functions are acceptable.
PMID- 25120653
TI - Tonsil neuroendocrine carcinoma concurrent with hepatocellular carcinoma: A case
report.
AB - The majority of neuroendocrine tumors appear to be sporadic. Neuroendocrine
carcinoma (NEC) typically arises in pancreatic, parathyroid and adrenal glands,
but rarely arises in salivary glands. NEC of the tonsil is a rare type of tumor
and the concurrent presentation of hepatocellular carcinoma (HCC) is considered
to be more uncommon. There are few case reports of NEC of the tonsil in the
literature and to date no studies have been conducted to establish its optimal
management. The current study presents a case of a 72-year-old male who presented
with left neck and tonsil tumors. A biopsy from the tonsil revealed a NEC, and
computed tomography showed liver cirrhosis, multiple liver cancers and portal
vein thrombosis, as well as metastasis to the hilar, abdomen and retroperitoneum.
Histological examination of the hepatic revealed primary HCC. To the best of our
knowledge, this is a condition that has not previously been reported.
PMID- 25120654
TI - Lung adenocarcinoma harboring L858R and T790M mutations in epidermal growth
factor receptor, with poor response to gefitinib: A case report.
AB - Lung cancer is the leading cause of mortality among malignant diseases in humans
worldwide. During the last decade, molecular targeted therapies for non-small
cell lung cancer using first-generation, reversible epidermal growth factor
receptor (EGFR) tyrosine kinase inhibitors (TKIs), including gefitinib, have been
shown to be a promising approach for patients harboring activating mutations in
EGFR. The current study reports a 77-year-old patient diagnosed with
adenocarcinoma harboring L858R and T790M point mutations in the EGFR gene. The
patient was treated with gefitinib as the second-line therapy, but no clinical
benefit was observed. As the majority of patients with lung cancer receiving EGFR
TKI therapy acquire resistance, repeated biopsies and detection of the EGFR
mutation state are beneficial for selecting appropriate treatments.
PMID- 25120656
TI - Human cytomegalovirus inhibits apoptosis by regulating the activating
transcription factor 5 signaling pathway in human malignant glioma cells.
AB - The activating transcription factor 5 (ATF5), also termed ATFx, is a member of
the ATF/cAMP response element-binding protein (CREB) family of basic zipper
proteins. ATF5 is an anti-apoptotic protein that is highly expressed in malignant
glioma and is essential for glioma cell survival. Accumulating evidence indicates
that human malignant gliomas are universally infected with human cytomegalovirus
(HCMV). Recent studies have shown that HCMV may be resistant to the induction of
apoptosis by disrupting cellular pathways in glioblastoma. To investigate the
potential anti-apoptotic function of HCMV in glioma, malignant U87 glioma cells
were infected with HCMV. The present study showed that HCMV infection suppressed
apoptosis in glioblastoma U87 cells by regulating the expression of ATF5.
Furthermore, in glioblastoma U87 cells, HCMV infection induced cellular
proliferation in parallel with an increase in the expression level of ATF5 and B
cell lymphoma/leukemia-2 to Bcl-2-associated X protein ratio. Loss of ATF5
function was achieved using a dominant-negative form of ATF5 in U87 cells,
whereby cells appeared to grow marginally following HCMV infection when compared
with the control. However, the anti-apoptotic ability was appeared to decline in
the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay.
These results indicate that ATF5 signaling pathways may be important in the anti
apoptotic activity of HCMV-infected glioblastoma cells; therefore, the anti
apoptotic molecular mechanisms of HCMV in human glioblastoma cells were
investigated in the current study. Prevention of HCMV infection may present a
potential and promising approach for the treatment of malignant gliomas.
PMID- 25120657
TI - Phosphatase and tensin homolog overexpression decreases proliferation and
invasion and increases apoptosis in oral squamous cell carcinoma cells.
AB - Phosphatase and tensin homolog (PTEN) is a potent tumor suppressor which
regulates various cellular functions. The aim of the present study was to analyze
the function of PTEN gene expression in squamous cell carcinoma (SCC) cells. This
gene exhibits a unique function in cell migration and proliferation during the
early stages of embryonic development. However, its role as a tumor suppressor
gene in tongue squamous carcinoma cells remains unclear. In the present study, an
SCC-4 cell line stably expressing PTEN was established and the effects of PTEN
gene expression on SCC-4 cell proliferation, invasion and apoptosis were
investigated. PTEN expression was found to induce apoptosis in SCC-4 cells,
possibly via negative regulation of the phosphatidylinositide 3-kinase/Akt
signaling pathway and increased expression of Bcl-2-interacting mediator of cell
death. In addition, PTEN was found to control the epithelial-mesenchymal
transition in SCC cells, thereby reducing their invasive ability. Furthermore,
Transwell assay revealed that the expression of E-cadherin was increased, while
the expression of vimentin and SNAIL was decreased. This study has provided an
important insight into the mechanisms by which PTEN mediates the progression and
early metastasis of tongue carcinoma.
PMID- 25120655
TI - miR-320a is an independent prognostic biomarker for invasive breast cancer.
AB - Breast cancer is one of the most common malignancies worldwide and is the second
leading cause of cancer-related mortality among females. miRNAs are a class of
small noncoding RNAs that are aberrantly expressed in human cancers. Due to their
small size and stability, miRNAs have the potential to be efficacious clinical
targets. MicroRNA-320a (miR-320a) has been shown to be dysregulated in multiple
malignancies. In the present study, the expression levels of miR-320a were
investigated in 15 paraffin-embedded in situ breast carcinoma and 130 invasive
breast cancer tissues, and the prognostic value for breast cancer patients was
assessed. Chromogenic in situ hybridization revealed that 60/130 (46%) invasive
breast cancer tissues exhibited high expression levels of miR-320a (staining
index score of >=4). Furthermore, miR-320a staining was found to significantly
correlate with tumor size (P=0.046), clinical stage (P<0.001), lymph node
metastasis (P<0.001) and distant metastasis (P=0.006). In addition, patients
exhibiting low miR-320a expression levels had shorter overall survival times
(P<0.001). Univariate and multivariate analyses revealed that miR-320a was an
independent prognostic biomarker for invasive breast cancer (hazard ratio, 0.221;
95% confidence interval, 0.050-0.979; P=0.047). Receiver operator characteristic
curves revealed that the prognostic value of miR-320a was enhanced when compared
with the widely used prognostic biomarkers (estrogen receptor, progesterone
receptor and human epidermal growth factor-2) in invasive breast cancer. The
results of the present study suggest that miR-320a presents a potential biomarker
for the prognosis of invasive breast cancer, and dysregulation of miR-320a may be
involved in invasive breast cancer progression.
PMID- 25120658
TI - Submucosal small-cell neuroendocrine carcinoma of the larynx detected using 18F
fluorodeoxyglucose positron emission tomography/computed tomography: A case
report and review of the literature.
AB - A 67-year-old male presented with a metastatic carcinoma in the right side of the
neck from an unknown primary site. 18F-fluorodeoxyglucose (FDG) positron emission
tomography/computed tomography showed increased 18F-FDG uptake in the right
larynx and right neck lymph nodes. A smooth lesion was identified in the
submucosa of the right supraglottic region via a suspension laryngoscopy under
general anaesthesia. A biopsy was performed and a frozen section revealed a small
cell (SC) carcinoma. A total laryngectomy and bilateral neck dissection were
performed simultaneously, and the pathological results demonstrated a SC
neuroendocrine carcinoma. The patient received chemo-radiotherapy
postoperatively, however, succumbed due to distant metastasis one year following
surgery.
PMID- 25120659
TI - Misdiagnosis of pancreatic papillary mucinous cystadenocarcinoma: A case report.
AB - The morbidity of papillary cystadenocarcinoma of the pancreas is extremely low
and the condition is rarely first found as spinal metastases, thus it is often
misdiagnosed prior to surgery. The present study reports a case of papillary
cystadenocarcinoma with thoracolumbar metastases in a 56-year-old male. The first
symptom to occur was backache, however, computed tomography revealed no positive
findings. The pain became exacerbated and the patient underwent lumbar and
thoracic vertebrae magnetic resonance imaging, which identified abnormal signals.
Imaging and pathological examinations were used for the final diagnosis. Due to
multiple bone metastases, the patient the administration of induction
chemotherapy was suggested, however, the patient refused. The patient succumbed
to the disease in June 2013.
PMID- 25120660
TI - Multifocal Langerhans cell histiocytosis in an adult with a pathological fracture
of the mandible and spontaneous malunion: A case report.
AB - Langerhans cell histiocytosis (LCH) is rare in the adult population and even
rarer with jaw involvement. The current study presents the case of a 39-year-old
male who complained of recurrent pain, swelling of the gingiva and an occasional
pus-like discharge in the right mandible for one year. The patient was previously
prescribed antibiotics, but this did not resolve the problem. An initial
panoramic radiograph showed an osteolytic lesion and bone fracture in the right
mandible. Eight months later, a new radiograph showed the spontaneous malunion of
the fractured mandible. The patient was eventually diagnosed with Langerhans cell
histiocytosis by histopathology and immunohistochemistry. Further lesions were
found in the ribs and ilium by nuclear bone scanning. The patient was
subsequently treated with systemic chemotherapy, and the lesions are currently
effectively being controlled. This study is the first to show that spontaneous
intralesional bone regeneration may lead to reunification of the mandible
fracture caused by LCH in an adult.
PMID- 25120662
TI - Shikonin promotes autophagy in BXPC-3 human pancreatic cancer cells through the
PI3K/Akt signaling pathway.
AB - The present study aimed to investigate the effect of shikonin on autophagy in
BXPC-3 human pancreatic cancer cells and its underlying mechanism. Cell viability
was assessed using the Cell Counting Kit-8 assay and the expression of light
chain (LC) 3, p62, phosphoinositide 3-kinase (PI3K), Akt, phosphorylated (p)-PI3K
and p-Akt was analyzed using western blot analysis. Following treatment with 1
MUmol/l shikonin for 48 h and 2.5 and 5 MUmol/l shikonin for 24 and 48 h, the
viability of the BXPC-3 cells was found to be significantly reduced and the
protein expression of LC3-II/LC3-I was observed to be increased, while the
protein expression of p62, PI3K, Akt, p-PI3K and p-Akt was decreased. These
findings suggest that shikonin promotes autophagy in BXPC-3 cells and that the
underlying mechanism may be associated with the PI3K/Akt signaling pathway.
PMID- 25120661
TI - Clinical significance of aberrant mammalian target of rapamycin expression in
stage IIIB colon cancer.
AB - The aim of the present study was to investigate the significance of aberrant
expression of mammalian target of rapamycin (mTOR) and the activated form of mTOR
kinase, phosphorylated mTOR (pmTOR), in human stage IIIB colon cancer. The
expression of mTOR and pmTOR was detected by immunohistochemistry in the tumor
tissue of stage IIIB colon cancer patients. The association between the
expression of mTOR, pmTOR and clinicopathological parameters of patients was
analyzed. The positive expression of mTOR and pmTOR was observed to be higher in
75.5% (80/106) and 76.4% (81/106) of the 106 colon cancer specimens, compared
with the adjacent normal tissues. The high level of pmTOR expression was found to
be significantly higher in the invasive tumor front cells and resulted in a
higher risk of mortality. The results suggested that mTOR and pmTOR may be
promising clinical markers and present novel molecular targets for designing
novel therapeutic strategies to treat this malignancy.
PMID- 25120663
TI - A 4-cm lipoma of the transverse colon causing colonic intussusception: A case
report and literature review.
AB - Colonic lipomas are rare benign tumors. Colonic intussusception is an uncommon
complication of colonic lipoma. The current study presents an unusual case of a 4
cm symptomatic lipoma of the transverse colon causing colonic intussusception. A
65-year-old female was admitted to Wenzhou Central Hospital (Wenzhou, Zhejiang,
China) with intermittent pain in the left abdomen that had been present for two
weeks. Colonoscopy revealed a 4*5-cm intraluminal spherical mass with erosional
mucosa 60 cm above the anal verge, indicating the presence of a malignant
gastrointestinal stromal tumor. Contrast-enhanced computed tomography revealed a
well-defined fatty tissue mass of 4 cm in diameter in the distal transverse colon
proximal to the splenic flexure, with intussusception. The patient underwent
segmental resection of the transverse colon and intraoperative frozen sections
were obtained. The intraoperative frozen sections revealed a submucosal lipoma of
the transverse colon and thus, a conclusive diagnosis was achieved. The patient
was followed up for one year and 10 months following the segmental resection of
the transverse colon, with a good prognosis. This study may increase clinical
awareness with regard to colonic lipomas. Furthermore, open surgery combined with
use of intraoperative frozen sections should be recommended for large symptomatic
colonic lipomas accompanied by colonic intussusception, thus avoiding unnecessary
radical resection and improving patient prognosis.
PMID- 25120664
TI - Polymorphism of the p38beta gene in patients with colorectal cancer.
AB - The p38 mitogen-activated protein kinase (MAPK) signaling pathways have been
proposed to participate in the pathological process of cancer by affecting
inflammation, proliferation, metastasis and cell survival. A single nucleotide
polymorphism (SNP; rs2235356, -1628A->G) in the promoter region of the p38beta
gene has been proposed as a genetic modifier for colorectal cancer (CRC) in a
Chinese population. The present study evaluated the susceptibility of patients
possessing this SNP to CRC, in addition to determining its association with
clinical parameters in Swedish patients with CRC. Using the LightSNiP genotyping
assay, this SNP was screened in 389 patients with CRC and 517 control subjects.
No significant difference in the genotype distribution or in the allelic
frequencies was identified between the two groups nor was any association
identified with the clinical parameters. These findings indicate that the -1628A
>G polymorphism of the p38beta gene is not significantly associated with a
susceptibility to CRC in a Swedish population.
PMID- 25120665
TI - Combination of autoantibodies against NY-ESO-1 and viral capsid antigen
immunoglobulin A for improved detection of nasopharyngeal carcinoma.
AB - Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in
Southern China and Southeast Asia, and early detection remains a challenge.
Autoantibodies have been found to precede the manifestations of symptomatic
cancer by several months to years, making their identification of particular
relevance for early detection. In the present study, the diagnostic value of
serum autoantibodies against NY-ESO-1 in NPC patients was evaluated. The study
included 112 patients with NPC and 138 normal controls. Serum levels of
autoantibodies against NY-ESO-1 and classical Epstein-Barr virus marker, viral
capsid antigen immunoglobulin A (VCA-IgA), were measured by enzyme-linked
immunosorbent assay. Measurement of autoantibodies against NY-ESO-1 and VCA-IgA
demonstrated a sensitivity/specificity of 42.9/94.9% [95% confidence interval
(CI), 33.7-52.6/89.4-97.8%] and 55.4/95.7% (95% CI, 45.7-64.7/90.4-98.2%),
respectively. The area under receiver operating characteristic curve for
autoantibodies against NY-ESO-1 (0.821; 95% CI, 0.771-0.871) was marginally lower
than that for VCA-IgA (0.860; 95% CI, 0.810-0.910) in NPC. The combination of
autoantibodies against NY-ESO-1 and VCA-IgA yielded an enhanced sensitivity of
80.4% (95% CI, 71.6-87.0%) and a specificity of 90.6% (95% CI, 84.1-94.7%).
Moreover, detection of autoantibodies against NY-ESO-1 could differentiate early
stage NPC patients from normal controls. Our results suggest that autoantibodies
against NY-ESO-1 may serve as a potential biomarker, as a supplement to VCA-IgA,
for the screening and diagnosis of NPC.
PMID- 25120666
TI - Extended curettage and heat ablation for desmoplastic fibroma of the distal femur
with a 12-year follow-up period: A case report.
AB - Desmoplastic fibroma is a particularly rare, benign but locally aggressive,
primary bone tumor. Owing to previously published reports stating high recurrence
rates following curettage, the recommended primary treatment for desmoplastic
fibroma is a marginal to wide tumor resection. In the current report, the case of
an athlete with desmoplastic fibroma of the distal femur who was treated with
extended curettage, heat ablation and artificial bone grafting is described. The
postoperative course was uneventful and no recurrence has been observed during
the 12-year follow-up period. The patient is able to sit on his heels with a
straight back, without pain and is able run a complete marathon.
PMID- 25120667
TI - Lymphatic invasion of micropapillary cancer cells is associated with a poor
prognosis of pathological stage IA lung adenocarcinomas.
AB - The cancer cells of lung adenocarcinoma with a micropapillary pattern (MPP) have
been found to frequently invade lymphatic vessels, and the prognosis of patients
with lung adenocarcinoma with an MPP is poor. In the present study, the cancer
cells of lung adenocarcinomas containing an MPP were found to express vimentin
more extensively than those in lung adenocarcinoma without an MPP. The
contribution of cancer cells in the MPP component to adenocarcinoma lymphatic
invasion was assessed using vimentin as a marker. Vimentin expression was
analyzed in the cancer cells present in each lymphatic vessel and compared with
the expression of vimentin in the cancer cells in the adenocarcinomas without an
MPP component. The results showed that the cancer cells in the lymphatic vessels
expressed vimentin more extensively than those in the adenocarcinoma components
without an MPP, suggesting that cancer cells derived from an MPP component are
present in the lymphatic vessels. By contrast, the area of the MPP component in
each adenocarcinoma was <25%. These findings suggest that cancer cells in MPP
components have a high capacity to invade lymphatic vessels and that their high
invasive capacity may be associated with a poor prognosis in patients with
adenocarcinoma with an MPP component.
PMID- 25120668
TI - Interleukin 4, interleukin 6 and osteopontin-serological markers of head and neck
malignancy in primary diagnostics: A pilot study.
AB - The progression of head and neck squamous cell carcinoma (HNSCC) is stimulated by
various angiogenic peptides and growth factors. A correlation between tumor
progression and the secretion of various serological mediators in patients with
malignant tumors of the head and neck is of major interest for tumor diagnostics,
evaluation of the therapy response and it may predict prognosis by specifying the
individual tumor biology. Established chemotherapeutic regimes for head and neck
tumors usually consist of platinum-based chemotherapeutic drugs and 5
fluorouracil (5-FU). The present pilot study sought to assess the eligibility of
seven serological factors as biomarkers for malignant tumors of the head and
neck: Platelet-derived growth factor, vascular endothelial growth factor,
epidermal growth factor receptor, osteopontin, granulocyte-colony stimulating
factor, interleukin-4 (IL-4) and IL-6. The serum levels of each factor in 20
patients receiving concomitant radiochemotherapy with cisplatin or carboplatin
and 5-FU with curative intent were determined prior and subsequent to
chemotherapy and were compared with 40 healthy controls. Another aim of the pilot
study was to investigate whether the serum of patients showed significant
differences in the concentrations of the analyzed factors at the start of
concomitant radiochemotherapy compared with the controls, whether those markers
indicated a neoplastic process and whether concomitant radiochemotherapy with
cisplatin or carboplatin and 5-FU induced significant alterations of
concentration compared with pre-therapeutic levels. The included patients were
histopathologically diagnosed with HNSCC and the average age was 62.3 years. The
serum samples of the patients were obtained during the course of regular pre- and
post-chemotherapeutic blood draws one week prior to the start of
radiochemotherapy and one week following the completion of chemotherapy. The
healthy controls were collected from patients of the Sleep Laboratory of the
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital
(Mannheim, Germany) without clinical evidence or laboratory signs of inflammation
or history of a malignant disease. The average age was 50.3 years. The
serological level of each factor was ascertained by enzyme-linked immunosorbent
assay in duplicate. Serum levels of IL-4, IL-6 and osteopontin were significantly
increased in patients with HNSCC compared with those in chemotherapy-naive
healthy controls. IL-4 and osteopontin showed no significant therapy-associated
alterations. Notably, IL-6 levels significantly increased post-therapeutically.
Using logistic regression with osteopontin and IL-4, an individual risk-profile
for random samples was calculated. IL-4, IL-6 and osteopontin appear to be
suitable indicators of the neoplastic process as they are significantly increased
in HNSCC patients compared with the control group. With the exception of IL-6,
whose levels were in fact increased following therapy, a significant therapy
associated alteration of these factors was missing. Therefore, these serological
markers failed to predict the therapy response, but they may be valuable as a
screening instrument in primary diagnostics.
PMID- 25120670
TI - Metachronous multiple gastrointestinal stromal tumors and adenocarcinoma of the
colon: A case report.
AB - Synchronous or metachronous occurrence of gastrointestinal stromal tumors (GISTs)
and other primary gastrointestinal neoplasms has previously been reported.
However, to the best of our knowledge, there are few studies regarding
metachronous multiple GISTs and adenocarcinoma of the colon. The current case of
an 80-year-old male patient who underwent a laparoscopic right hemicolectomy for
colonic adenocarcinoma, located in the ascending colon, is presented. Twenty-one
months after receiving the laparoscopic right hemicolectomy, two new disc-like
bulge lesions in the descending colon and rectosigmoid were identified during an
endoscopic follow-up examination, and a segmental bowel resection was performed.
The final diagnosis of multiple colonic GISTs was established as a result of
histopathological examination and immunohistochemistry.
PMID- 25120669
TI - Polypoid colonic metastases from gastric stump carcinoma: A case report.
AB - The present study aimed to investigate polypoid colonic metastases from gastric
stump carcinoma by performing a retrospective analysis of the clinical data of a
patient with such a diagnosis, and by discussing other previous case studies from
the literature. The patient of the present study was an 80-year-old male who had
undergone a gastrectomy 48 years previously for a benign perforated gastric
ulcer. A colonoscopy revealed >10 multiple polypoid lesions of 6-10 mm in
diameter distributed throughout the entire colon, except in the rectum. Each
lesion had either erosion or a depression at the top and several were covered
with a white fur-like substance. Biopsy specimens excised from the stomach showed
a poorly-differentiated adenocarcinoma with diffuse signet ring cells, and a
colonoscopy-guided biopsy revealed a signet ring cell adenocarcinoma. The patient
was referred to the Oncology unit (Beijing Shijitan Hospital, Beijing, China) for
assessment and chemotherapy treatment, which was initiated with 1,000 mg Xeloda
orally administered twice a day for two-week courses every three weeks. The
patient succumbed to upper gastrointestinal hemorrhage and pneumonia after three
months. Gastric or gastric stump carcinoma may metastasize to the colon
presenting as solitary or multiple colonic polyps. Thus, it is important to
consider this diagnosis as such colon metastases may mimic solitary or multiple
colonic polyps, which are commonly observed. A differential diagnosis is required
in this complicated situation.
PMID- 25120672
TI - Inflammatory cytokines induce vascular endothelial growth factor-C expression in
melanoma-associated macrophages and stimulate melanoma lymph node metastasis.
AB - Lymph node colonization by tumor cells is one of the key determinants of melanoma
staging and prognosis, and tumor-associated macrophages (TAMs) are the
predominant type of inflammatory cell in the tumor environment which secretes
vascular endothelial growth factor (VEGF)-C, the most potent lymphangiogenic
growth factor. In the present study, to elucidate the mechanism involved in VEGF
C expression in TAMs, murine peritoneal macrophages were co-cultivated with
syngeneic B16 melanoma cells to mimic the reciprocal interactions between tumor
cells and macrophages found in spontaneous tumors. In the present study, upon
contact with tumor cells, macrophages were found to express a higher level of
VEGF-C which was associated with an increase in the expression of IL-1beta and
TNF-alpha and their receptors. Antibodies against the IL-1beta and TNF-alpha
receptors were added to media that had been conditioned by the macrophage-tumor
cell co-cultures and inhibition of VEGF-C was observed in macrophages co
cultivated with the tumor cells. Furthermore, when IL-1beta and TNF-alpha were
used at a non-toxic level, they enhanced peritoneal lymph node colonization by
melanoma cells. Thus, in the present study, macrophagic IL-1beta and TNF-alpha
were observed to promote VEGF-C expression in TAMs, as well as melanoma lymph
node metastasis, suggesting that inhibiting the signaling between tumor cells and
TAMs may be required to inhibit lymphangiogenesis and lymph node metastasis.
PMID- 25120671
TI - Undifferentiated embryonal liver sarcoma in childhood: A case report.
AB - In order to improve the diagnosis and therapy of undifferentiated embryonal liver
sarcoma (UELS), the present study presents the case of a 9-year-old female with
UELS and discusses UELS in childhood. The patient presented with abdominal pain
and fever. The laboratory tests, radiographic examination and pathological
features presented by the female were similar to those of typical cases of UELS
reported in childhood. The patient initially received surgical treatment and the
immunohistochemical findings suggested that the patient had UELS. The patient's
parents refused adjuvant chemotherapy and demonstrated a right prerenal mass 6
months post-surgery. Microscopic examination revealed that the tumor was evidence
of undifferentiated embryonal sarcoma recurrence. However, the patient was
comfortable and physical examination revealed no abnormal conditions. In
addition, the laboratory results were normal. Abdominal computed tomography scan
and ultrasound were performed every 3 months to monitor the tumor recurrence. At
the time of writing, it has been 6 months after the second surgical procedure and
there has been no appearence of abnormalities. Previous studies have shown that
patients who receive combined therapy with complete tumor resection and adjuvant
chemotherapy have a longer survival time than those who undergo surgical therapy
alone. Complete tumor resection combined with adjuvant chemotherapy may reduce
the risk of recurrence and enhance the survival time in patients with UELS.
PMID- 25120674
TI - Chemotherapy-induced fulminant acute pancreatitis in pancreatic carcinoma: A case
report.
AB - Cases of chemotherapy-induced pancreatitis are rarely reported and among those
diagnosed, the majority are mild and self-limiting. However, no previous cases of
fulminant acute pancreatitis (FAP) induced by chemotherapeutic agents have been
reported. The current study presents a case of FAP in a 62-year-old female on
gemcitabine and capecitabine therapy. The patient was admitted to the China-Japan
Friendship Hospital (Beijing, China) with the symptoms of acute pancreatitis two
days after the completion of the first cycle of chemotherapy. Shock, hypoxemia
and acute renal failure supervened, which resulted in mortality. As the common
etiologies of pancreatitis were eliminated, a correlation between the incidence
of FAP, and pancreatic cancer or chemotherapy, or both was suspected. Clinicians
should be aware of this potential adverse effect when prescribing
chemotherapeutic agents, particularly in patients with pre-existing risk factors
for pancreatitis.
PMID- 25120673
TI - Effect of daphnoretin on the proliferation and apoptosis of A549 lung cancer
cells in vitro.
AB - Daphnoretin is an active constituent of Wikstroemia indica C.A. Mey., which is
widely distributed in the northwest and southwest regions of China. Previous
studies have shown that daphnoretin has anticancer effects on leukemia,
osteosarcoma and uterine cervix cancer cells. However, the effect of daphnoretin
on human lung cancer cells has yet to be elucidated. In the present study,
daphnoretin was observed to inhibit A549 lung cancer cell proliferation in a
concentration- and time-dependent manner. Fluorescent microscopy and flow
cytometric analysis showed that daphnoretin induced A549 cell apoptosis in a
concentration-dependent manner. Western blot analysis also revealed that
daphnoretin induced apoptosis through the regulation of the B-cell lymphoma-2
gene family in A549 cells. These findings indicate that daphnoretin may have
potential as a therapeutic agent for the management of lung cancer.
PMID- 25120675
TI - Primary adrenal nodular lymphocyte-predominant Hodgkin lymphoma: A case report
and review of the literature.
AB - Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a subtype of Hodgkin
lymphoma (HL), and is a rare disease manifestation in the adrenal gland, which is
difficult to be diagnosed and treated. In the present study, we report a case of
primary adrenal NLPHL in a 36-year-old male patient. The patient was without
specific clinical signs and the definitive diagnosis was achieved by histological
study. The patient underwent a laparoscopic left adrenalectomy and chemotherapy
regimen of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). There is
no standard treatment for adrenal NLPHL and therefore, treatment is based on that
for other types of NLPHL, which includes radiotherapy and ABVD chemotherapy.
Given the rarity of this disease, there are limited experiences with regard to
its diagnosis and treatment. This study is useful for the differential diagnosis
and treatment of adrenal masses.
PMID- 25120676
TI - Primary chondrosarcoma presenting as an intrathoracic mass: A report of three
cases.
AB - Primary intrathoracic chondrosarcomas are rare tumors. The present study reports
three cases of primary intrathoracic chondrosarcomas in two males and one female
aged between 45 and 64 years. Clinically, one case presented with cough and blood
sputum, while the other two cases of primary intrathoracic chondrosarcoma were
found incidently during a routine health examination. Radiologically, the
chondrosarcomas presented as large masses with intratumoral calcification.
Chondrosarcoma should be distinguished from other calcified pulmonary lesions. In
this study, all three cases underwent surgical treatment, and in one case, the
surgery was accompanied by radiotherapy. To date, all patients have been followed
up for between two and three years and are alive.
PMID- 25120677
TI - Epithelioid angiosarcoma of the kidney: A case report and literature review.
AB - Epithelioid angiosarcoma (EAS) is a rare disease which presents a great
diagnostic challenge. The present study reports a case of EAS in the kidney in a
75-year-old male who presented with gross hematuria. An abdominal computed
tomography scan revealed space-occupying lesions of the right kidney and renal
cell carcinoma was suspected. Histological examination of the resected specimens
showed pleomorphic epithelioid cells with vesicular nuclei, prominent nucleoli
and eosinophilic cytoplasm that lined irregular vascular spaces.
Immunohistochemical staining revealed that the tumor cells were positive for
AE1/AE3, cytokeratin (CK) 7, vimentin, cluster of differentiation (CD) 31 and E
cadherin, but showed no staining for CD10, CD34, factor VIII, CK20,
carcinoembryonic antigen or desmin. Based on the histopathological and
immunohistochemical findings, the patient was diagnosed with epithelioid
angiosarcoma. Postoperative radiation therapy was administered and no recurrence
was observed six months after surgery.
PMID- 25120678
TI - Imaging observations of a schwannoma of low malignant potential in the anterior
abdominal wall: A case report.
AB - Neurilemmoma, also known as schwannoma, is an uncommon benign neoplasm that is
most commonly found in the trunk and head and neck regions. The present study
reports the case of a 67-year-old female with schwannoma localized in the
anterior abdominal wall and analyzes the ultrasound and computed tomography (CT)
imaging observations of the schwannoma. A dynamic time-intensity curve was also
recorded in the study. A well-defined, elliptic low echo level, heterogeneous
mass was observed during ultrasound examination. The CT scan revealed a solid,
heterogeneous, low-density mass in the abdominal wall. Contrast-enhanced scans
showed a heterogeneously enhanced mass during the arterial and venous phase.
Centripetal fill-in was demonstrated and the mass was markedly, homogenously
enhanced relative to the muscles during the delayed phase. Peak enhancement was
observed during the venous phase and then slowly declined. However, the mass was
hyperattenuated during the delayed phase. The lesion was completely excised and
no evidence of recurrence has been identified during the 3 months of follow-up.
The present study suggested that a diagnosis of schwannoma should be considered
for certain patients with masses in the abdominal wall. Peripheral enhancement
during the arterial and venous phases and homogeneous enhancement in the delayed
phase are the significant imaging findings of a schwannoma.
PMID- 25120679
TI - Never in mitosis gene A-related kinase 6 promotes cell proliferation of
hepatocellular carcinoma via cyclin B modulation.
AB - Never in mitosis gene A-related kinase (Nek) 6 is a recently identified Nek that
is required for mitotic cell cycle progression; however, the role and mechanism
of Nek6 activity during hepatocarcinogenesis is not well known. The aim of this
study was to investigate the potential roles and internal mechanism of Nek6 in
hepatocellular carcinoma (HCC) development. In the present study, Nek6 was found
to be overexpressed in HCC samples and cell lines by florescent real-time
quantitative polymerase chain reaction, immunohistochemistry and western blot
analysis. Furthermore, it was evidenced to contribute to oncogenesis and
progression. The ectopic overexpression of Nek6 promoted cell proliferation and
colony formation, whereas gene silencing of Nek6 inhibited these phenotypes, as
documented in Huh7, PLC/PRF/5, Hep3B and HepG2 HCC cell lines. Mechanistic
analyses indicated that Nek6 regulates the transcription of cyclin B through cdc2
activation, and promotes the accumulation of G0/G1-phase cells. In conclusion,
the findings of the current study suggested that Nek6 contributes to the
oncogenic potential of HCC, and may present as a potential therapeutic target in
this disease.
PMID- 25120680
TI - Expression of WASF3 in patients with non-small cell lung cancer: Correlation with
clinicopathological features and prognosis.
AB - Wiskott-Aldrich syndrome protein family member 3 (WASF3) is required for invasion
and metastasis in different cancer cell types, and has been demonstrated to
possess prognostic value in various types of human cancer. However, to the best
of our knowledge, the expression profile of WASF3 and its correlations with the
clinicopathological features of non-small cell lung cancer (NSCLC) have not yet
been described. In the present study, the mRNA expression levels of WASF3, in 38
NSCLC patients and in matched normal tissues, were assessed using quantitative
polymerase chain reaction and the protein expression in 96 specimens was analyzed
using immunohistochemistry. In addition, patient survival data were collected
retrospectively and the association between WASF3 expression and five-year
overall survival was evaluated. The results demonstrated that the mRNA expression
level of WASF3 in cancer tissues was markedly (approximately five times) higher
compared with that of the normal tissues. The WASF3 protein expression profile in
NSCLC was consistent with the mRNA expression result, which also correlated with
the histological subtype and tumor stage. Furthermore, patients with WASF3
positive expression were associated with a poorer prognosis compared with those
exhibiting WASF3-negative expression, and the five-year survival rate was 20.8
and 46.5%, respectively (Kaplan-Meier; log-rank, P=0.004). In the multivariate
analysis, which included other clinicopathological features, WASF3 emerged as an
independent prognostic factor (relative risk, 0.463; 95% CI, 0.271-0.792). These
results indicate that WASF3 may be critical in the pathogenesis of NSCLC, in
addition to being a valuable prognostic factor for NSCLC patients. Further
investigations are required to identify the efficacy of WASF3 as a potential
therapeutic target for the treatment of NSCLC.
PMID- 25120681
TI - Nicotinamide N-methyltransferase is overexpressed in prostate cancer and
correlates with prolonged progression-free and overall survival times.
AB - Nicotinamide N -methyltransferase (NNMT) has been identified to be associated
with tumorigenesis and the malignant transformation of numerous types of cancer.
The aim of the present study was to explore the expression and prognostic
significance of NNMT in prostate cancer (PCa). Immunohistochemical NNMT
expression was examined in 26 cases of benign prostate hyperplasia (BPH), 18
cases of high-grade prostatic intraepithelial neoplasia (HGPIN) and 120 cases of
PCa. While rarely expressed in BPH (8/26 cases; 30.8%), NNMT was found to be
significantly upregulated in HGPIN (15/18 cases; 83.3%) and PCa (77/120 cases;
64.2%). Clinicopathological analysis revealed that NNMT expression was negatively
correlated with Gleason score (P<0.001). Furthermore, Kaplan-Meier survival
curves revealed that high NNMT expression was associated with prolonged
progression-free survival (PFS) and overall survival (OS) times in patients with
advanced PCa. Multivariate analysis showed that NNMT was an independent
prognostic marker of PFS and OS in patients with advanced PCa. The results of the
present study suggested that NNMT may contribute to the development of PCa and
may potentially be a favorable prognostic marker for the survival of patients
with advanced PCa.
PMID- 25120682
TI - Periductal stromal sarcoma of the breast: A case report and review of the
literature.
AB - Periductal stromal sarcoma (PSS), spindle and epithelioid types, is a rare
subtype of malignant fibroepithelial tumor. The morphological characteristics of
this neoplasm are different from phyllodes tumor and stromal sarcoma. PSS
exhibits biphasic histology with benign ductal elements and a sarcomatous stroma
composed of spindle cells and lacking phyllodes tumor architecture. The
therapeutic management of PSS is based on wide surgery with free margins, and
adjuvant therapies are not required. To the best of our knowledge, the recurrence
of PSS in <=5 months has not been reported in the literature to date. This report
describes a 43-year-old woman who presented to our hospital with a recurrence of
nodules in the left breast. The patient had undergone lumpectomy at a different
hospital 5 months previously, and a diagnosis of phyllodes tumor was
pathologically confirmed. On presentation at our hospital, the patient underwent
a second lumpectomy. Histological examination revealed PSS and the patient
underwent a simple mastectomy of the left breast with no adjuvant treatment (such
as chemotherapy or radiotherapy). After 9 months of close follow-up examinations,
no recurrence was observed. PSS is an extremely rare disease with low-grade
sarcomatous behavior, which may evolve into a phyllodes tumor or an entity of
breast cancer. Therefore, frequent follow-up examinations are required.
PMID- 25120683
TI - Undifferentiated embryonal sarcoma of the liver mistaken for hepatic abscess in
an adult.
AB - Undifferentiated embryonal sarcoma of the liver (UESL) predominantly occurs in
children under the age of 10 years, and ~90% of cases occur in children <15 years
old. Patients may complain of abdominal pain, fever or other symptoms. No
significant decrease has been identified in the hepatic function or elevation of
alpha-fetoprotein, which differentiates UESL from primary carcinomas of the
liver. In the present study, a rare and misdiagnosed case of an UESL arising in a
male, which was mistaken for a hepatic abscess and retrospectively re-diagnosed,
is reported. This case was misdiagnosed as a hepatic abscess initially, and it
was diagnosed as UESL subsequent to performing tests, including a type-B
ultrasonic scan and computed tomography (CT), and evaluating pathological
findings. The rapid recurrence of the tumor in this patient was identified by CT,
and this is associated with the malignancy of the disease. Currently, patients
with UESL have a poor prognosis as there is not a successful treatment strategy.
The present study analyzes the course of diagnosis and potential treatment for
the disease.
PMID- 25120684
TI - Ovarian steroid cell tumor, not otherwise specified: A rare case of
postmenopausal vaginal bleeding.
AB - Ovarian steroid cell tumors (SCTs), not otherwise specified (NOS) are
particularly rare ovarian tumors, which are composed of steroid-hormone secreting
cells. The majority of patients with this tumor produce excessive quantities of
testosterone and virilization is common. The current report presents a rare case
of SCT in a 59-year-old female who presented with postmenopausal vaginal
bleeding. The patient had experienced irregular vaginal bleeding for two months,
12 years after menopause. Transvaginal ultrasound and magnetic resonance imaging
identified a solid adnexal mass and the pathological result of diagnostic
curettage showed a proliferative endometrium. The patient's serum estrogen and
testosterone levels were elevated (393.71 nmol/l and 22.28 nmol/l, respectively).
The patient underwent an exploratory laparotomy, hysterectomy and
bisalpingectomy. The neoplasm was well-circumscribed, solid, homogeneous and
yellow in color. Microscopically, the tumor was predominantly composed of
granular eosinophilic or vacuolated cytoplasm. Reinke's crystals, prominent
nucleoli and Call-Exner bodies were not observed, and there was no mitotic
figure. Immunohistochemistry demonstrated that the tumor cells were strongly
positive for inhibin. The present rare case aims to expand the current knowledge
of this type of ovarian tumor.
PMID- 25120685
TI - Expression of Kin17 promotes the proliferation of hepatocellular carcinoma cells
in vitro and in vivo.
AB - Kin17 protein is ubiquitously expressed in mammals and is correlated with vital
biological functions. However, little is known about the role of Kin17 in the
proliferation of hepatocellular carcinoma cells. The aim of the present study was
to investigate whether the upregulation of Kin17 can promote the growth of
hepatocellular carcinoma cells. A series of assays was performed to study the
effect of Kin17 in the proliferation of hepatocellular carcinoma cells in vitro
and in vivo. The western blotting results revealed that Kin17 expression was
increased in hepatocellular carcinoma tissues compared with that of the
corresponding normal tissues. Moreover, ectopic upregulation of Kin17 expression
promoted the growth of hepatocellular carcinoma cells in vitro and in vivo. These
results indicated that Kin17 is involved in the tumorigenesis of hepatocellular
carcinoma, and that Kin17 has the potential to serve as a therapeutic target for
hepatocellular carcinoma.
PMID- 25120686
TI - B7-H3 and B7-H1 expression in cerebral spinal fluid and tumor tissue correlates
with the malignancy grade of glioma patients.
AB - The B7 family consists of activating and inhibitory molecules that regulate
immune responses. Recent research demonstrated the roles of soluble B7-H3 (sB7
H3) and soluble B7-H1 (sB7-H1) in the blood serum of various tumors; however,
none of these studies investigated the expression of these proteins in the
cerebral spinal fluid (CSF) and blood serum of patients with glioma. The aim of
the present study was to investigate the expression of B7-H3 and B7-H1 in the
CSF, blood serum and tissues of patients with glioma and their correlation with
clinicopathological data. Between January 2012 and November 2012, samples were
obtained from 78 patients with glioma, four CSF samples were obtained from
patients with a moderate traumatic brain injury, four brain tissue samples were
obtained from patients with a traumatic brain injury and 40 blood serum samples
were obtained from healthy individuals. The expression of B7-H3 and B7-H1 in the
CSF, blood serum and tumor samples of the patients with high-grade glioma was
found to be higher than that in the patients with low-grade glioma. However, no
significant differences in sB7-H3 and sB7-H1 expression were observed in the
blood serum of the patients with glioma compared with the healthy control
subjects. In addition, the expression of sB7-H3 and sB7-H1 in the CSF of the
patients with glioma was higher than that in the CSF of the patients with a
moderate traumatic brain injury. Furthermore, in the patients with glioma, B7-H3
and B7-H1 expression in the CSF and tumor tissue, although not in the blood
serum, correlated with the glioma grade.
PMID- 25120687
TI - Dermatofibrosarcoma protuberans of the breast: A case report.
AB - Dermatofibrosarcoma protuberans (DFSP) is a rare, metastasizing tumor of the deep
dermis and subcutaneous tissue. While it frequently occurs in the trunk and
extremities, breast involvement has rarely been reported. In the present case,
imaging and pathological technologies were used to detect DFSP of the breast.
Surgical excision with wide margins (>3 cm) and pathology revealed spindle cells
arranged in storiform patterns and short fascicles which were crucially CD34
positive, enabling a definitive diagnosis prior to surgery.
PMID- 25120688
TI - Breast cancer metastasis to the stomach confirmed using gastroscopy: A case
report.
AB - Breast cancer metastasis to the stomach is relatively rare. Unlike infiltrating
ductal carcinoma, invasive lobular carcinoma (ILC) has a high tendency to
metastasize to the stomach. The present study reports a case of a 53-year-old
female who had undergone a modified radical mastectomy of the left breast for ILC
eight years previously and presented at the clinic seeking treatment for
epigastric discomfort from sour regurgitation and belching that had persisted for
one month. Gastroscopy revealed multiple apophysis lesions in the stomach, which
were diagnosed as metastatic tumors to the stomach. The diagnosis was further
established using histological and immunohistochemical analyses for gross cystic
disease fluid protein-15, cytokeratin (CK) 7 and CK20. The patient was treated
with systemic chemotherapy without surgery. During the treatment, two gastroscopy
procedures revealed that the apophysis lesions in the gastric body had narrowed
significantly. Few cases of breast cancer metastasizing to the stomach have been
reported, particularly those that have been confirmed using gastroscopy. The
present study reports a case of breast cancer metastasis to the stomach to raise
awareness of the condition.
PMID- 25120690
TI - Progression of penile cutaneous horn to squamous cell carcinoma: A case report.
AB - The current report presents the case of a 43-year-old male suffering from a
penile cutaneous horn. A surgical excision of the lesion was performed and
histopathology demonstrated hyperkeratosis, dyskeratosis and epithelial
hyperplasia. The cutaneous horn progressed to squamous cell carcinoma <1.5 months
following surgery and a partial penectomy was conducted. The International Index
of Erectile Function 5 questionnaire was used to assess the patient and the score
had decreased in the one-month postoperative follow-up compared with that of the
preoperative period. These findings indicate that undergoing a partial penectomy
on initial diagnosis of a penile cutaneous horn should be considered in order to
conserve a greater quantity of the penile tissue and improve the postoperative
quality of life.
PMID- 25120689
TI - Sarcomatoid carcinoma of the renal pelvis: A case report.
AB - Sarcomatoid carcinoma is a high-grade malignant neoplasm which exhibits
morphological and/or immunohistochemical evidence of bidirectional epithelial and
mesenchymal differentiation. Sarcomatoid carcinoma occurring in the upper urinary
tract is rare. The present study reports a case of primary sarcomatoid carcinoma
of the renal pelvis. A 49-year-old female patient was admitted to Beijing Chao
Yang Hospital for experiencing two weeks of intermittent hematuria. A computed
tomography scan revealed a mass of 2 cm in diameter in the left renal pelvis. A
retroperitoneoscopic nephroureterectomy combined with a bladder cuff excision was
performed, and the final pathological diagnosis was sarcomatoid carcinoma of the
renal pelvis. The patient did not receive systemic chemotherapy and radiotherapy.
Regular follow-up was performed for 30 months, and there was no evidence of tumor
local recurrence or distant metastasis.
PMID- 25120691
TI - Metastasis of mesothelioma to the maxillary gingiva.
AB - Malignant mesothelioma predominantly arises from the serosal surfaces of the
pleural or peritoneal cavity. There is currently no effective standard treatment
for mesothelioma and the prognosis for patients is poor; the majority of patients
with malignant mesothelioma succumb between 12 and 17 months following diagnosis.
The association of all forms of malignant mesothelioma with asbestos exposure has
been well documented. However, metastasis to the oral gingiva is rare, as only
four cases have previously been reported; two cases of metastasis to the tongue
and four cases to the jaw bone. In the current report, the case of a 62-year-old
male with metastatic mesothelioma is presented. To the best of our knowledge,
this is the first report regarding the metastasis of this type of neoplasm to the
maxillary gingiva.
PMID- 25120692
TI - Biological characteristics of prostate cancer cells are regulated by hypoxia
inducible factor 1alpha
AB - Hypoxia-inducible factor (HIF)-1alpha has been reported to be associated with
malignancy in a number of types of cancer. However, the role of HIF-1 alpha in
the regulation of prostate cancer (PCa) growth has yet to be elucidated. The
present study aimed to investigate the effect of HIF-1alpha on the biological
characteristics of the PCa PC3 cell line. Full-length (fL) HIF-1alpha and
dominant-negative (dn) HIF-1alpha were transfected into PC3 cells. The expression
of HIF-1alpha and its downstream genes, including vascular endothelial growth
factor (VEGF), erythropoietin (EPO) and CXC chemokine receptor 4 (CXCR4), were
detected using western blot analysis. Cell proliferation, apoptosis and migration
were assessed using MTT, terminal deoxynucleotidyl transferase-mediated dUTP nick
end labeling and Boyden chamber assays. The expression of VEGF, EPO and CXCR4 was
found to be upregulated in the fL HIF-1alpha-transfected PC3 cells and
downregulated in the dn HIF-1alpha-transfected PC3 cells. The overexpression of
HIF-1alpha was observed to enhance cell proliferation and migration and decrease
docetaxol-induced cell apoptosis. However, dn HIF-1alpha was found to attenuate
cell proliferation and migration, and promote docetaxol-induced cell apoptosis.
These findings indicate that HIF-1alpha regulates the proliferation, apoptosis
and migration of PC3 cells, at least in part, by regulating the expression of its
target genes, including VEGF, EPO and CXCR4. Thus, the use of HIF-1alpha
inhibitors may be a promising therapy for the treatment of PCa.
PMID- 25120693
TI - XRCC2 rs3218536 polymorphism decreases the sensitivity of colorectal cancer cells
to poly(ADP-ribose) polymerase 1 inhibitor.
AB - Single nucleotide polymorphisms (SNPs) are associated with the development of
certain types of cancer. The present study aimed to investigate the association
between X-ray repair complementing defective repair in Chinese hamster cells 2
(XRCC2) SNPs and colorectal cancer (CRC) cell sensitivity to the poly(ADP-ribose)
polymerase (PARP) 1 inhibitor olaparib (AZD2281). SNaPshot(r) analysis of XRCC2
SNPs was performed in five CRC cell lines. The AZD2281-sensitivities of the CRC
cells were also analyzed using MTT assays. The effect of AZD2281 on XRCC2 and
PARP1 expression was investigated in the five cell lines using quantitative
polymerase chain reaction and western blot analyses. Parallel investigations were
performed using a cisplatin (DDP) model of DNA damage. The XRCC2 rs3218536 SNP
was found to be associated with the LoVo microsatellite instability CRC cell
line. The relative rate of growth inhibition was found to be lower in the LoVo
cells following treatment with AZD2281 compared with the other four cell lines
(P=0.002). Furthermore, the XRCC2 mRNA level in the LoVo cells was observed to be
significantly higher than that in the other four cell lines (P<0.05). Similar
results were found using the DDP model of DNA damage (P<0.05). The present study
indicated that the XRCC2 rs3218536 polymorphism decreases the sensitivity of CRC
cells to AZD2281.
PMID- 25120696
TI - Laparoscopic radiofrequency ablation-assisted enucleation of Xp11.2 translocation
renal cell carcinoma: A case report.
AB - The current study presents a case of Xp11.2 translocation renal cell carcinoma
(Xp11.2 RCC) in a 30-year-old female. The patient was referred to The Affiliated
Drum Tower Hospital of the Medical College of Nanjing University (Nanjing,
Jiangsu, China) due to a right renal tumor without evident symptoms, which was
found by a routine physical examination. A computed tomography (CT) scan
indicated that the mass exhibited cystic and solid components. The patient
underwent laparoscopic radiofrequency ablation-assisted enucleation.
Immunohistochemistry revealed intense nuclear staining for transcription factor
E3 protein in the cancer cells. The patient was diagnosed with Xp11.2 RCC. The
urological and radiological outcomes remained satisfactory after >2.5 years of
follow-up.
PMID- 25120695
TI - Conservative management of endometrial stromal sarcoma at stage III: A case
report.
AB - Endometrial stromal sarcoma (ESS) is a rare malignant tumor of the uterus. The
standard treatment is surgery, such as total hysterectomy with bilateral salpingo
oophorectomy. The use of adjuvant treatment, including chemotherapy, radiation
therapy and endocrine therapy, remains controversial, so it is uncommon for
conservative management to be performed in patients with low-grade ESS. The
present study reports the case of a 19-year-old female with ESS at stage III who
underwent a local mass resection by laparoscopic surgery. A high dose of
progestin (medroxyprogesterone acetate) therapy was then administered.
Conservative management resulted in complete remission of the low-grade ESS, with
no sign of recurrence at the 33-month follow-up.
PMID- 25120694
TI - Implications of PPPDE1 expression in the distribution of plakoglobin and beta
catenin in pancreatic ductal adenocarcinoma.
AB - Human PPPDE peptidase domain-containing protein 1 (PPPDE1) is a recently
identified protein; however, its exact functions remain unclear. In our previous
study, the PPPDE1 protein was found to be decreased in certain cancer tissues. In
the present study, a total of 96 pancreatic ductal carcinoma tissue samples and
31 normal tissues samples were assessed to investigate the distribution of
plakoglobin and beta-catenin under the conditions of various PPPDE1 expression
levels by means of immunohistochemistry. Generally, the staining of PPPDE1 was
strong in normal tissues, but weak in cancer tissues. Plakoglobin was mainly
distributed along the membrane and cytoplasm border in normal cells, but was less
evident in the membranes of cancer cells. In particular, a greater percentage of
cells exhibited low membrane plakoglobin expression in cancer tissue with low
PPPDE1 expression (PPPDE1-low cancer) compared with that in cancer tissue with
high PPPDE1 expression (PPPDE1-high cancer). The distribution of beta-catenin in
normal tissues was similar to that of plakoglobin. However, beta-catenin was
peculiarly prone to invade nucleus in PPPDE1-low cancer compared with PPPDE1-high
cancer. Our data suggested potential links between PPPDE1 expression and the
distribution of plakoglobin and beta-catenin in pancreatic ductal adenocarcinoma,
providing insights into the role of PPPDE1 in the progression of pancreatic
cancer.
PMID- 25120697
TI - Osteosarcoma arising from the parapharyngeal space: A case report.
AB - The current study presents a rare case of osteoblastic osteosarcoma arising from
an extremely rare site, namely, the parapharyngeal space. To the best of our
knowledge, this is the first study of computed tomography (CT) and magnetic
resonance imaging (MRI) of an osteosarcoma in the parapharyngeal space with
pathological correlation. A 56-year-old male presented with a mass of the right
facial region. CT and MRI showed a heterogeneous mass, with ossification or
calcification, occupying the parapharyngeal space. Open biopsy revealed an
osteoblastic osteosarcoma containing calcified malignant osteoid. Lung CT also
showed multiple lung metastases at the time of the first visit to the Department
of Orthopedic Surgery, Osaka City University Graduate School of Medicine (Osaka,
Japan). Systemic chemotherapy and radiotherapy were administered to the patient
for palliation. The patient was alive at the 24-month follow-up subsequent to
this treatment. Although a definitive diagnosis requires the use of a biopsy, the
CT and MRI findings described in the present study suggest inclusion of this rare
tumor in the differential diagnosis that is formed when such findings occur in
the parapharyngeal space. The present study also briefly discusses osteosarcoma
of the parapharyngeal space.
PMID- 25120698
TI - Traumatic breast transposal to the abdominal wall: A case report.
AB - Although abdominal wall masses are commonly observed in clinical practice,
traumatic breast transposal appearing as an abdominal wall mass is a rare event.
The unique phenomenon of a post-traumatic breast growing healthily in the
abdominal wall has never previously been reported. The current study presents the
case of a 40-year-old female who developed an unusually transposed, but healthy
mammary gland in the right upper abdominal wall following a severe pedestrian
traffic accident. In that accident, the powerful impact of the car caused
multiple right-sided rib fractures, lung injuries and a protruding mass on the
right abdominal wall. This sudden onset protruding mass was indicated to be
breast tissue by computed tomography imaging and ultrasound scanning. The
transposed mammary gland was resected and a pathological examination confirmed
that it consisted of normal breast tissue. In this case, the force of the car
caused no significant damage or necrosis to the right breast, but instead was
sufficient to shift the mammary gland to the abdomen, where it grew healthily 6
months in its new location. This case highlights the capability of the mammary
gland to withstand a powerful impact and survive. Moreover, it advances our
knowledge of how mammary tissues respond to severe blunt-force impacts.
PMID- 25120703
TI - Primary intraosseous carcinoma arising from an odontogenic cyst: A case report.
AB - Cyst-like lesions in the mandible rarely develop into malignancies, and the
reported incidence is between 0.3 and 2%. The present study describes a rare case
of primary intraosseous squamous cell carcinoma of the mandible arising from an
odontogenic cyst. A 59-year-old female was referred to Asahi University Murakami
Memorial Hospital (Gifu, Japan), with acute pain in the right molars. An initial
examination revealed buccal swelling and paresthesia of the mental nerve.
Following an intraoral examination, the oral mucosa was confirmed to be normal,
however, percussion pain was experienced between the lower right first premolar
and second molar. Panoramic radiography revealed a retained lower right wisdom
tooth and an irregular radiolucent area between the lower right molar and a
mandibular angle with unclear margins. Computed tomography revealed diffuse bone
resorption and an extensive loss of cortical bone on the buccal and lingual
sides. A biopsy was performed and the pathological diagnosis was of a squamous
cell carcinoma arising from the epithelial lining of the odontogenic cyst.
Radical dissection was subsequently performed, however, histopathological
examination of the resected specimen revealed neither invasion into the
surrounding tissues penetrating the periosteum nor lymph node metastasis at the
right submandibular lesion. Following the pathological diagnosis of primary
intraosseous carcinoma (PIOC), the patient received 6,000 Gy radiation as post
operative radiotherapy and chemotherapy with oral administration of tegafur,
gimeracil and oteracil potassium. The patient is currently undergoing follow-up
examinations. Although PIOC arising from an odontogenic cyst is rare, it should
be considered as a differential diagnosis for radiolucency of the jaw bone,
particularly in older patients exhibiting a history of cystic lesions.
PMID- 25120705
TI - Primary neuroendocrine small cell carcinoma of the parotid gland: A case report
and review of the literature.
AB - Small cell carcinoma (SCC) is a malignant epithelial tumor that predominantly
arises in the lungs. Primary SCC of the parotid gland is rare and difficult to
diagnose by analysis of frozen sections obtained during surgery. Due to the
aggressive nature of SCC and the frequent occurrence of distant metastases,
identification of the disease is important. The current study reports the case of
a male patient who presented with a right parotid gland mass. The tumor was
resected and evaluated by light microscopy and immunohistochemical analysis.
Immunohistochemically, the tumor was positive for cytokeratin, epithelial
membrane antigen, cluster of differentiation 117, synaptophysin and thyroid
transcription factor-1, which indicated that the tumor was a SCC of the parotid
gland. An extended resection of the right parotid gland mass and dissection of
the facial nerve were performed. Following discharge from the hospital, the
patient received radiation therapy postoperatively. The patient has remained
disease free during five months of follow-up.
PMID- 25120699
TI - Giant primary cystic mediastinal lymphangioma: A case report.
AB - Cystic lymphangioma mainly occurs in children. Cystic mediastinal lymphangioma
(CML) originates from mediastinal tissues and is an extremely uncommon cystic
lymphangioma that develops from the lymphatic vessels. The present study reports
the case of 46-year-old male patient with a giant CML that was surgically
resected by video-assisted thoracoscopy. The largest diameter of the CML was 18.0
cm, and ~400 ml of pale yellow fluid was removed from the cystic cavity during
surgery. The postoperative pathological reports on the cystic wall showed that
the neoplasm was a CML. At present, at the one-year postoperative follow-up,
there are no signs of recurrence. In conclusion, complete surgical resection may
prevent recurrence.
PMID- 25120702
TI - Isolated duodenal myeloid sarcoma associated with the CBFbeta/MYH11 fusion gene
followed by acute myeloid leukemia progression: A case report and literature
review.
AB - Myeloid sarcoma (MS) is a rare disease that presents as an extramedullary
tumorous mass of immature myeloid precursors. The majority of MS are identified
in acute myeloid leukemia (AML) patients and rarely present as a primary isolated
MS without AML. In addition, inversion of chromosome 16 [inv(16)] and the
CBFbeta/MYH11 fusion gene are rarely associated with MS. The current study
reports a female patient with an isolated duodenal MS, who developed AML-M4
associated with the CBFbeta/MYH11 fusion gene and 48,XX,inv(16),+13,+22. A review
of previously reported cases of isolated MS with the CBFbeta/MYH11 fusion gene
was also performed. Isolated MS with the CBFbeta/MYH11 fusion gene was often
observed in abdominal lesions, with the intestinal tract being the predominantly
involved site. In addition, patients with isolated MS with the CBFbeta/MYH11
fusion exhibited a high risk of developing systemic AML. The diagnosis of
isolated MS may be particularly challenging and, therefore, determining the
optimal standard treatment for isolated MS is required.
PMID- 25120701
TI - Association between four common microRNA polymorphisms and the risk of
hepatocellular carcinoma and HBV infection.
AB - microRNAs (miR/miRNAs) have been demonstrated to function as tumor suppressors
and oncogenes, and miRNA polymorphisms may have a role in cancer development. The
present study aimed to investigate the association between the miR-146aG>C, miR
149C>T, miR-196a2C>T and miR-499A>G polymorphisms and the risk of hepatocellular
carcinoma (HCC) and hepatitis B virus (HBV) infection. A total of 271 patients
with HCC and 532 healthy control participants were enrolled in the present study.
miR-146aG>C, miR-149C>T, miR-196a2C>T and miR-499A>G polymorphisms were genotyped
using the polymerase chain reaction-restriction fragment length polymorphism
method. A significant difference was identified in the genotype frequency of miR
196a2C>T in the patients in the case group compared with the control group
(chi2=6.88; P=0.032). Compared with the CC genotype, the miR-196a2 TT genotype
was associated with a significantly reduced risk of HCC [odds ratio (OR), 0.62;
95% confidence interval (CI), 0.38-0.99], and a significantly reduced risk was
also found in the dominant (OR, 0.69; 95% CI, 0.49-0.98) and recessive (OR, 0.70;
95% CI, 0.46-1.02) models. Moreover, individuals with HBV who were carrying the
miR-196a2 CT and TT genotypes had a significantly reduced risk of HCC (OR, 0.62;
95% CI, 0.41-0.95; and OR, 0.39; 95% CI, 0.20-0.73, respectively). In conclusion,
the present study found that the miR-196a2C>T polymorphism has a protective
effect in patients with HCC, particularly in those with HBV infection.
PMID- 25120700
TI - Mutation analysis of key genes in RAS/RAF and PI3K/PTEN pathways in Chinese
patients with hepatocellular carcinoma.
AB - The RAS/RAF and PI3K/PTEN signaling pathways play central roles in
hepatocarcinogenesis. KRAS, NRAS, HRAS, BRAF, PIK3CA, PIK3R1 and PTEN are key
cancer-related genes in the RAS/RAF and PI3K/PTEN signaling pathways. Genetic
alterations in these genes often lead to the dysregulation of the two cascades.
Little is known regarding the frequency of hotspot mutations in these critical
components among Chinese patients with hepatocellular carcinoma (HCC). In the
current study, 57 somatic hotspot mutations in 36 HCCs samples collected from
Chinese patients using direct DNA sequencing method were examined. Two cases of
KRAS somatic mutations (KRAS codon 61; Gln to His) were identified among 36 HCCs
(5.6%). However, no mutations were found in the NRAS, HRAS, BRAF, PIK3CA, PIK3R1
and PTEN genes. These findings indicated that point mutations in the KRAS gene,
but not mutations in NRAS, HRAS, BRAF, PIK3CA, PIK3R1 and PTEN genes, at a
somatic level contribute to the abnormal activation of the RAS/RAF and PI3K/PTEN
pathways in HCC.
PMID- 25120704
TI - Metformin inhibits the proliferation of A549/CDDP cells by activating p38 mitogen
activated protein kinase.
AB - Metformin (Met) has been widely used in hypoglycemic therapy, and it is also able
to reduce the incidence of tumors and tumor-related mortality. The present study
investigated whether Met could inhibit the proliferation of lung cancer cells and
enhance the sensitivity of a cisplatin-resistant lung cancer A549/CDDP cell line
to cisplatin. It was found that Met treatment inhibited the proliferation of
different lung cancer cells. Met inhibited the cell cycle of the A549/CDDP cells
and induced apoptosis. Upon Met treatment, the A549/CDDP cells were arrested at
the G1 phase. The apoptosis of the A549/CDDP cells was confirmed by the
appearance of apoptotic bodies in cells stained with Hoechst 33258, and by the
cleavage of BH3 interacting-domain death agonist and poly (ADP-ribose)
polymerase. Furthermore, results showed that the phosphorylation level of p38
mitogen-activated protein kinase (MAPK) was increased after Met treatment. The
p38 MAPK inhibitor, SB203580, significantly blocked Met-induced apoptosis in the
A549/CDDP cells. It was further demonstrated that Met could enhance the
sensitivity of the A549/CDDP cells to cisplatin. In summary, the present study
identified Met as a drug sensitizer that could improve the treatment effect of
cisplatin in cisplatin-resistant lung cancers.
PMID- 25120706
TI - Ovarian hyperstimulation in premenopausal women during adjuvant tamoxifen
treatment for endocrine-dependent breast cancer: A report of two cases.
AB - Adjuvant endocrine therapy is an integral component of care for endocrine
dependent breast cancer. The aim of this type of therapy is to counteract the
production and the action of estrogens. The ovary is the primary site of estrogen
production in premenopausal women, whereas, in postmenopausal women, the main
source of estrogens is adipose tissue. Therefore, ovarian function suppression is
an effective adjuvant strategy in premenopausal estrogen-dependent breast cancer.
Similarly, the inhibition of estrogen action at the receptor site by tamoxifen
has proven to be effective. To date, international consensus statements recommend
tamoxifen (20 mg/day) for five years as the standard adjuvant endocrine therapy
for premenopausal women. It should be noted that tamoxifen is a potent inducer of
ovarian function and consequent hyperestrogenism in premenopausal women. In the
present study, we report two cases of ovarian cyst formation with very high
estrogen levels and endometrial hyperplasia during the administration of
tamoxifen alone as adjuvant treatment for estrogen receptor-positive breast
cancer in premenopausal women. These cases suggest that in young premenopausal
patients with estrogen-dependent breast cancer, ovarian suppression is an
essential prerequisite for an adjuvant endocrine therapy with tamoxifen. In this
context, luteinizing hormone-releasing hormone agonist treatment by suppressing
effective ovarian function may lead to a hypoestrogenic status that may
positively impact breast cancer prognosis and prevent the effects of tamoxifen at
the gynecological level. It is important to reconsider the action of tamoxifen on
ovarian function and include these specific effects of tamoxifen in the informed
consent of premenopausal patients who are candidates for tamoxifen alone as
adjuvant endocrine treatment.
PMID- 25120707
TI - Oral malignant melanoma: A report of two cases with BRAF molecular analysis.
AB - Primary oral malignant melanoma is a rare condition, accounting for 1.3-1.4% of
all melanomas, usually presenting with an aggressive clinical behavior. The
present study reports the clinicopathological findings of two cases of oral
malignant melanoma and discusses the epidemiology, diagnosis and current
therapeutic approaches for this uncommon condition. In the first case the patient
presented with a pigmented lesion located on the lower mucosal lip. The patient
showed no nodal metastases and therefore, underwent a wedge resection. After
seven months, the patient presented with neck lymph nodes and multiple visceral
metastases. Molecular analysis of BRAF, using a pyrosequencing approach, revealed
the presence of BRAF V600E mutation. The patient developed multiple visceral
metastases, but refused treatment and was lost to follow-up. In the second case,
no BRAF V600E mutation was found, but the patient exhibited a pigmented patch in
the lower gingival mucosa, which was excised by surgical treatment. The patient
was followed up by an oncologist, but did not undergo an additional therapy and
is currently alive with no evidence of visceral metastases at one year following
the diagnosis.
PMID- 25120708
TI - Basaloid squamous cell carcinoma of the maxillary gingiva: A case report and
review of the literature.
AB - Basaloid squamous cell carcinoma (BSCC) is a rare, but distinct histologic
variant of squamous cell carcinoma in the head and neck region. It is considered
to have a poor prognosis due to its aggressive behavior and tendency to
metastasize. The usual sites of BSCC are the floor of the mouth, hypopharynx and
base of the tongue, and according to the English-language literature its
presentation in the gingiva is somewhat uncommon. In the current report, the
unusual case of a 40-year-old male is presented; the patient exhibited a painless
irregular mass in the maxillary gingiva, which infiltrated the maxillary sinus,
as observed by computed tomography. Hematoxylin and eosin-stained sections
revealed a diagnosis of BSCC with typical central necrosis in the cancer nests,
which contained basaloid and squamous cells. Immunohistochemistry revealed that
p63 was weakly positive, high molecular weight cytokeratin (CK) was focally
positive, and S-100, CK7, CK14 and vimentin were negative. It must be noted that
histopathology results may be incorrectly interpreted as adenoid cystic
carcinoma, undifferentiated carcinoma and basal cell adenocarcinoma.
PMID- 25120709
TI - Meningeal myofibroblastoma in the frontal lobe: A case report.
AB - Myofibroblastoma is a benign tumor composed of spindle cells in clusters and
fascicles. To date, only three cases of intracranial myofibroblastoma have been
reported. The present study reports the case of a 47-year-old female with
meningeal myofibroblastoma. The patient had a history of ovarian cyst resection
and presented with paroxysmal mild headaches that had been apparent for 4 years.
Magnetic resonance imaging disclosed a well-circumscribed mass in the left
frontal lobe. A resection of the mass was performed. Abundant fascicular clusters
of spindle- and oval-shaped cells were found by conventional histopathology.
Immunohistochemical staining demonstrated that these cells were strongly positive
for smooth muscle actin, weakly positive for epithelial membrane antigen and
negative for cluster of differentiation (CD)117, CD34, S-100 or desmin, with a Ki
67 index of >10%. These results supported the diagnosis of myofibroblastoma. No
recurrence of the mass was found during the 24-month follow-up period. Overall,
the patient exhibited a rare type of meningeal neoplasm. Resection of the tumor
proved to be successful and no recurrence were found. Histopathological and
immunohistochemical staining is crucial to form a diagnosis. To the best of our
knowledge, the present study is the first to show the presence of
myofibroblastoma in the left frontal lobe.
PMID- 25120710
TI - Icotinib inhibits the invasion of Tca8113 cells via downregulation of nuclear
factor kappaB-mediated matrix metalloproteinase expression.
AB - Icotinib is an epidermal growth factor receptor tyrosine kinase inhibitor, which
has been revealed to inhibit proliferation in tumor cells. However, the effect of
icotinib on cancer cell metastasis remains to be explained. This study examines
the effect of icotinib on the migration and invasion of squamous cells of tongue
carcinoma (Tca8113 cells) in vitro. The results of the Boyden chamber invasion
assay demonstrated that icotinib reduced cell invasion, suppressed the protein
levels of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, and increased the
expression of tissue inhibitor of metalloproteinase-1. In addition, icotinib was
found to significantly decrease the protein levels of nuclear factor kappaB (NF
kappaB) p65, which suggested that icotinib inhibits NF-kappaB activity.
Furthermore, treatment with the NF-kappaB inhibitor, pyrrolidine dithiocarbamate,
suppressed cell invasion and MMP-2 expression. These results suggested that
icotinib inhibits the invasion of Tca8113 cells by downregulating MMP via the
inactivation of the NF-kappaB signaling pathways.
PMID- 25120711
TI - Late-onset sarcoidosis in a patient with gastric mucosa-associated lymphoid
tissue non-Hodgkin lymphoma: A case report.
AB - The simultaneous presence of hematological malignancies and sarcoidosis, defined
as sarcoidosis-lymphoma syndrome, has been reported in 79 patients in the
literature to date. The majority of these patients were affected by sarcoidosis
and developed non-Hodgkin lymphoma or acute leukemia after 1-2 years; however, in
<20 cases the malignancy developed first. This report presents the case of an 83
year-old male with a clinical history of Helicobacter pylori-positive gastric
mucosa-associated lymphoid tissue lymphoma. The patient developed sarcoidosis 10
years after the first diagnosis, which caused the diagnostic work-up and
differential diagnosis between a lymphoma relapse and de novo sarcoidosis to be
challenging.
PMID- 25120712
TI - Maintenance therapy with capecitabine in patients with locally advanced
unresectable pancreatic adenocarcinoma.
AB - Therapeutic options for locally advanced pancreatic cancer (LAPC) include
concurrent chemoradiation, induction chemotherapy followed by chemoradiation or
systemic therapy alone. The original Gastro-Intestinal Study Group and Eastern
Cooperative Oncology Group studies defined fluorouracil (5-FU) with concurrent
radiation therapy followed by maintenance 5-FU until progression, as the standard
therapy for this subset of patients. Although this combined therapy has been
demonstrated to increase local control and median survival from 8 to 12 months,
almost all patients succumb to the disease secondary to either local or distant
recurrence. Our earlier studies provided a strong rationale for the use of
capecitabine in combination with concurrent radiation followed by maintenance
capecitabine therapy. To report our clinical experience, we retrospectively
evaluated our patients who were treated with maintenance capecitabine. We
reviewed the medical records of patients with LAPC who received treatment with
capecitabine and radiation, followed by a 4-week rest, then capecitabine alone
1,000 mg twice daily (ECOG performance status 2 or age >70 years) or 1,500 mg
twice daily for 14 days every 3 weeks until progressive disease. We treated 43
patients between September 2004 and September 2012. The population consisted of
16 females and 25 males, with a median age of 64 years (range, 38-80 years).
Patients received maintenance capecitabine for median duration of 9 months
(range, 3-18 months). The median overall survival (OS) for these patients was 17
months, with two patients still living and receiving therapy. The 6-month
survival rate was 91% (39/43), 1-year survival rate was 72% (31/43) and 2-year OS
rate was 26% (11/43). Grade 3 or 4 toxicity was observed rarely: Hand-foot
syndrome (HFS) in two patients, diarrhea in one patient and peripheral neuropathy
in one patient, and there was no mortality directly related to treatment.
Capecitabine maintenance therapy following chemoradiation in LAPC offers an
effective, tolerable and convenient alternative to 5-FU. To the best of our
knowledge, this is the largest study of its kind which has determined the safety
and efficacy of capecitabine maintenance therapy for patients with LAPC.
PMID- 25120713
TI - Crosstalk between the p38 and TGF-beta signaling pathways through TbetaRI,
TbetaRII and Smad3 expression in plancental choriocarcinoma JEG-3 cells.
AB - Choriocarcinoma is a highly aggressive tumor that develops from germ cells. Some
choriocarcinomas originate in the testes or ovaries, while others may develop in
the uterus after a normal pregnancy or after miscarriage. The tumor is
characterized by early hematogenous spread to distal organs, such as the lung and
brain. Transforming growth factor beta1 (TGF-beta1) is key in regulating tumor
cell proliferation and invasion through a variety of Smad-dependent and
independent pathways, including the p38 mitogen-activated protein kinase (MAPK)
pathway. There appears to be crosstalk between the TGF-beta/Smad and p38 MAPK
pathways; however, the molecular mechanisms underlying the crosstalk are not
fully understood. The present study validated the role of TGF-beta signaling in
cancer progression and explored the interaction between Smad and p38 MAPK
signaling on transduction mediators in choriocarcinoma using the JEG-3 cell line.
MTT assay was used to detect the effect of TGF-beta1 on JEG-3 cell proliferation.
Cells were treated with p38 MAPK inhibitor and TGF-beta receptor inhibitor,
followed by TGF-beta1, and reverse transcription quantitative real-time
polymerase chain reaction was used to examine the transcriptional levels of Smad3
and TGF-beta receptors. The data demonstrated that TGF-beta can enhance the
viability of JEG-3 cells. Blockade of the TGF-beta and p38 MAPK pathways
attenuated the expression of Smad3, TGF-beta receptor type I (TbetaRI) and
TbetaRII, and inhibited their expression in a dose-dependent manner. Analysis
revealed that p38 MAPK is involved in and contributes to the TGF-beta pathway,
dependent on the regulation of TbetaRI, TbetaRII and Smad3. Further investigation
of the interactions between the TGF-beta and p38 MAPK pathways may offer
potential venues for therapeutic intervention for choriocarcinoma.
PMID- 25120715
TI - Laparoscopic liver biopsy in the diagnosis of hepatic epithelioid
hemangioendothelioma: A case report.
AB - Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of the
liver, and its definitive diagnosis is completely dependent on histopathological
verification. In the present study, we report the case of a patient whose
percutaneous liver biopsy failed to reveal a diagnosis of HEH, twice, and who was
ultimately diagnosed by laparoscopic liver biopsy. The patient was a 42-year-old
female with mild right upper quadrant discomfort. Ultrasonography and magnetic
resonance imaging showed multiple mass lesions scattered throughout the liver,
but no evidence of extrahepatic diseases. The initial laboratory tests included
liver function tests and tumor markers were within normal limits. Subsequently,
two, ultrasound (US)-guided liver biopsies from the liver lesion were performed
using an 18-gauge needle, and both of these showed massive hepatocellular
necrosis. To obtain adequate tissue samples for histological examination, the
patient underwent laparoscopic liver biopsy. The overall immunohistochemical
findings supported the diagnosis of HEH. In the present case, two, US-guided
percutaneous liver biopsies failed to diagnose HEH, and laparoscopic liver biopsy
was safely performed to obtained adequate specimens for analysis. Although this
method is not the preferred technique and has certain disadvantages, it is
considered to be a useful and minimally invasive approach for liver lesions when
other less-invasive diagnostic modalities fail or are difficult to be performed.
PMID- 25120714
TI - Tracheal adenoid cystic carcinoma mimicking a thyroid tumor: A case report.
AB - At present, only eight cases of tracheal adenoid cystic carcinomas (ACCs)
mimicking thyroid tumors have been reported. Since there are no guidelines
available regarding their diagnosis and treatment, they present a significant
clinical challenge. In the present study, patient treatment was analyzed to
deliver the first concise summary of treatment options in patients with ACC
mimicking a thyroid tumor. In addition, all available data regarding molecular
abnormalities of this disease have been discussed. The current study presents a
case of a 17-year-old patient with a tracheal ACC mimicking a thyroid tumor. The
patient was diagnosed in 2007 with a pathological mass between the left lobe of
the thyroid and the trachea, and underwent surgery and radiotherapy. In 2010,
multiple lesions in the lungs were diagnosed and pulmonary metastasectomy was
performed. Following surgery, the patient has been disease-free for almost 30
months. Thyroid tumor biopsy may reveal ACCs. This pathological report requires
further investigation of the head and neck in order to confirm if the disease is
of tracheal origin. Patients may present with a neck swelling, hoarseness of
voice or dysphagia. Surgery must be considered as first-line therapy for all
patients with local disease as it may be curative. For palliative treatment
chemoradiotherapy based on cisplatin may be effective. The identification of
cytogenetics, tumor suppressor genes, oncogenes, epigenetic alterations and
mitochondrial abnormalities specific for ACCs is critical to the development of
targeted therapies. Thus far, large studies have only reported the
transcriptional activator Myb and mammalian target of rapamycin signaling pathway
to be disrupted in ACCs.
PMID- 25120716
TI - High efficacy of gefitinib in the treatment of EGFR mutation-positive advanced
non-small cell lung adenocarcinoma: A case report.
AB - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such
as gefitinib and erlotinib, are known to play a significant role in EGFR mutation
positive non-small cell lung cancer. When an EGFR mutation is found, gefitinib
and erlotinib have been shown to have significant roles in the treatment of
untreated advanced NSCLC. This study reports an EGFR mutation in NSCLC treated
with gefitinib and is notable due to the patient's marked improvement following a
shorter than average duration of treatment with gefitinib. The present study
reports the case of a 58-year-old male smoker with a dry cough. Computed
tomography revealed a mass in the left inferior lobe of the lung. The patient was
subsequently diagnosed with advanced lung adenocarcinoma, and an EGFR mutation
(in-frame deletions of E746-A750 in exon 19) was found. The patient received
multiple rounds of chemotherapy, followed by gefitinib maintenance therapy for 3
months. Later on, a grade 1 acne-like rash developed on the face and back that
lasted throughout the treatment. Currently, the patient is stable, with no
evidence of disease progression. The present study describes the disease and the
treatment using gefitinib.
PMID- 25120717
TI - Cathepsin D serum and urine concentration in superficial and invasive
transitional bladder cancer as determined by surface plasmon resonance imaging.
AB - Determination of cathepsin D (Cat D) concentration in serum and urine may be
useful in the diagnosis of bladder cancer. The present study included 54 healthy
patients and 68 patients with bladder cancer, confirmed by transurethral
resection or cystectomy. Cat D concentration was determined using a surface
plasmon resonance imaging biosensor. Cat D concentration in the serum of bladder
cancer patients was within the range of 1.3-5.59 ng/ml, while for healthy donors
it was within the range of 0.28-0.52 ng/ml. In urine, the Cat D concentration of
bladder cancer patients was within the range of 1.35-7.14 ng/ml, while for
healthy donors it was within the range of 0.32-0.68 ng/ml. Cat D concentration
may represent an efficient tumor marker, as its concentration in the serum and
urine of transitional cell carcinoma patients is extremely high when compared
with healthy subjects.
PMID- 25120718
TI - A large odontogenic myxoma of the bilateral maxillae: A case report.
AB - Odontogenic myxomas (OMs) are benign mesenchymal locally aggressive neoplasms of
the jaw bone. Although OMs predominantly involve the mandible, maxillary tumors
are usually more aggressive than mandibular tumors. The present study describes
the case of a 37-year-old male with a large odontogenic myxoma of the bilateral
maxillae, which caused a defect in the right skull base bone. The tumor was
successfully removed through radical resection of the hard tissue and local
resection around the envelope of the soft tissue. The tumor exhibited no
recurrence. However, the current methods for bilateral maxillary reconstruction
to restore the maxillary buttress and achieve an optimal aesthetic appearance are
complicated due to the lack of suitable conditions for oral rehabilitation with
good dentition.
PMID- 25120719
TI - Clinical significance of serum soluble death receptor 5 concentration in locally
advanced non-small cell lung cancer patients.
AB - There is an urgent requirement for the identification of suitable biomarkers for
the diagnosis and prognosis of non-small cell lung cancer (NSCLC). The present
study aimed to measure the levels of serum soluble death receptor 5 (sDR5) in
patients with locally advanced stage III NSCLC, and to evaluate its diagnostic
and prognostic significance in these patients. The sDR5 concentrations were
evaluated by the enzyme-linked immunosorbent assay method in 50 healthy controls
and 122 patients with locally advanced stage III NSCLC [including 57
adenocarcinoma (ADC) and 65 squamous cell carcinoma (SCC) patients], before and
after concurrent chemoradiotherapy. It was found that the pretreatment sDR5
levels in patients with NSCLC were higher than the sDR5 levels of healthy
controls (P<0.001). However, no significant difference in the sDR5 levels was
observed between the ADC and SCC subgroups (P=0.874). According to multiple
clinical classifications, a significant increase in the pretreatment serum sDR5
levels could be observed in IIIB-stage patients compared with IIIA-stage patients
(P=0.009). Patients with a tumor burden >3 cm had higher pretreatment sDR5
concentration than those with a tumor burden <=3 cm (P=0.026). Additionally, T4
stage patients had significantly higher pretreatment sDR5 levels compared with
those of T1-stage patients (P<0.001). There were no significant differences
between pre- and post-treatment sDR5 concentrations in the total NSCLC patient
group (P=0.462), ADC subgroup (P=0.066) and SCC subgroup (P=0.052). Furthermore,
when patients were divided according to therapeutic response, the pretreatment
sDR5 levels in the responder patients were significantly lower compared with
those of the non-responders (P<0.001). Further survival analysis showed that the
patients whose pretreatment sDR5 levels were <=14 pg/ml (cutoff value, 14 pg/ml)
had a longer progression-free survival (PFS) time than patients with sDR5 levels
>14 pg/ml. However, no correlation was observed between the post-treatment sDR5
levels and therapeutic response or PFS time. To the best of our knowledge, the
present study results provide the first evidence that the pretreatment serum
levels of sDR5 may be a useful biomarker for the diagnosis, prediction and
prognosis of patients with locally advanced stage III NSCLC.
PMID- 25120720
TI - Serum secreted frizzled-related protein 5 levels differentially decrease in
patients with hepatitis B virus-associated chronic infection and hepatocellular
carcinoma.
AB - The aim of this study was to investigate the characteristics of serum secreted
frizzled-related protein 5 (SFRP5), an inhibitor of Wnt signaling, in hepatitis B
virus (HBV)-associated infections and hepatocellular carcinoma (HCC) patients.
Serum SFRP5 levels were detected in 147 patients with HBV-associated chronic
infection or HCC. Compared with the non-HBV-infected and non-HCC group, the HBV
associated chronic infection and HCC groups exhibited decreased serum SFRP5
levels. A significant inverse correlation between serum SFRP5 levels and HBV DNA
levels was identified in the HBV-associated chronic infection and HCC groups.
Furthermore, SFRP5 levels differentially decreased in patients with HBV
associated diseases, in a manner which was dependent on liver disease status.
Compared with patients exhibiting HBV-associated chronic infection, patients with
HCC were found to exhibit lower serum SFRP5 levels. The results of the present
study indicated that patients with HBV-associated liver infection and HCC
exhibited significantly deceased serum SFRP5 levels, which were found to
negatively correlate with HBV DNA levels. Serum SFRP5 levels may present a
biomarker for the severity of HBV-associated liver infection, and the risk of HCC
initiation and progression.
PMID- 25120721
TI - Metaplastic breast carcinoma development following surgical resection of an
inflammatory myofibroblastic tumor in the right breast: A case report.
AB - Inflammatory myofibroblastic tumors (IMTs) are uncommon, mesenchymal lesions, and
malignant transformation is extremely rare. The current study presents the case
of a 56-year-old female with a rapidly growing mass in the right breast, which
was diagnosed as IMT. Immunohistochemically, the mass was positive for smooth
muscle actin (SMA) and Ki-67 (positive staining in 30% of the cells), and
negative for S-100, cluster of differentiation (CD)34, p63 and cytokeratin.
Malignant transformation to metaplastic carcinoma of the spindle-cell type was
observed following surgical resection. This metaplastic carcinoma demonstrated
positive immunoreactivity for cytokeratin, vimentin, CD34, p63 and Ki-67 (>30%),
and was negative for cytokeratin 7, SMA, desmin and S-100. The patient underwent
total mastectomy of the right breast, followed by palliative chemotherapy with
capecitabine; however, the patient succumbed to the disease after 12 weeks. The
unusual case presented in the current study emphasizes the importance of pre
operative examinations to determine the benign or malignant nature of IMTs, which
aids in the choice of appropriate surgical procedures.
PMID- 25120723
TI - 10058-F4, a c-Myc inhibitor, markedly increases valproic acid-induced cell death
in Jurkat and CCRF-CEM T-lymphoblastic leukemia cells.
AB - Adult T-cell acute lymphoblastic leukemia (T-ALL) has a poor prognosis. Although
it has been found that activation of Notch1 signaling occurs in >50% T-ALL
patients, gamma-secretase inhibitors that target Notch1 signaling are of limited
efficacy. However, c-Myc is an important direct target of Notch1 and, thus, c-Myc
is another potential therapeutic target for T-ALL. Valproic acid (VPA), a histone
deacetylase inhibitor, has been reported to treat various hematological
malignancies. In the present study, we showed that c-Myc expression, at a
transcriptional level, was dose-dependently downregulated in VPA-induced growth
inhibition in T-ALL cell lines, Jurkat and CCRF-CEM cells. 10058-F4, a small
molecule c-Myc inhibitor, could increase the downregulation of c-Myc and markedly
increase the growth inhibition and cell death induced by VPA in Jurkat and CCRF
CEM cells, which was accompanied by obvious cleavage of capase-3. Z-VAD-FMK, a
caspase inhibitor, partially prevented the anti-leukemic effect. The results of
the present study suggest that c-Myc inhibitors increase cell death induced by
VPA in a caspase-dependent and -independent manner, and their combination could
be a potent therapeutic strategy for adult T-ALL patients.
PMID- 25120724
TI - PIN1 promoter polymorphism (-842 G>C) contributes to a decreased risk of cancer:
Evidence from meta-analysis.
AB - Peptidyl-prolylcis-trans isomerase NIMA-interacting 1 (encoded by the PIN1 gene)
regulates the conformation of proline-directed phosphorylation sites and is
important in the etiology of cancer. Since the identification of a functional
polymorphism of PIN1, (-842 G>C; rs2233678), in the PIN1 promoter region,
numerous studies have evaluated the association between the PIN1 promoter
polymorphism (-842 G>C) and cancer risk. However, the available results are
inconclusive. To derive a more precise estimation, a meta-analysis of seven
previous case-control studies was performed, which included 4,524 cases
exhibiting different tumor types and 4,561 control subjects. The published
literature was retrieved from PubMed and EMBASE. Crude odds ratios (ORs) with 95%
confidence intervals (CIs) were calculated to evaluate the strength of the
association. Overall, the results of the present study demonstrated that
individuals carrying the variant C allele (G/C and C/C) were associated with a
significantly decreased cancer risk (OR, 0.75; 95% CI, 0.62-0.90 for GC vs. GG;
OR, 0.75; 95% CI, 0.64-0.88 for GC/CC vs. GG). In further stratified analyses, a
decreased cancer risk was observed in the following subgroups: Breast and lung
cancer patients, Asian individuals, and in studies with a sample size >500. The
results indicated that the PIN1 promoter polymorphism (-842 G>C; rs2233678)
contributes to a decreased risk of cancer via attenuating the transcriptional
activity.
PMID- 25120722
TI - Synergy of 1,25-dihydroxyvitamin D3 and carboplatin in growth suppression of SKOV
3 cells.
AB - 1alpha,25-Dihydroxyvitamin D3 [1,25(OH)2D3] has been demonstrated to inhibit the
growth of cancer cells. However, carboplatin is the most widely used
chemotherapeutic agent to treat cancer. We hypothesized that vitamin D may
enhance the antiproliferative effects of carboplatin, and tested this hypothesis
in ovarian cancer SKOV-3 cells treated with carboplatin and 1,25(OH)2D3. Cell
viability was determined by Cell Counting Kit-8, while cell cycle distribution,
apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential
(MMP) were analyzed by flow cytometry. In these experiments, 1,25(OH)2D3 and
carboplatin each provided dose-dependent suppression of SKOV-3 growth, and
synergy was demonstrated between 10 nM 1,25(OH)2D3 and carboplatin. The
proportion of cells in G0/G1 phase was markedly reduced by the drug combination,
while the proportion of cells in G2/M phase was increased. Apoptosis did not
increase in ovarian cancer cells treated with 10 nM 1,25(OH)2D3 alone; however,
1,25(OH)2D3 evidently enhanced carboplatin-induced apoptosis. Similarly, ROS
production was evidently higher and MMP was lower in cells treated with the two
drugs than in those treated with each drug alone. The results suggested that
1,25(OH)2D3 suppresses SKOV-3 growth and enhances the antiproliferative effect of
carboplatin. The drugs function synergistically by inducing cell cycle arrest,
increasing apoptosis and ROS production, and reducing MMP.
PMID- 25120725
TI - Claudin-4 expression in gastric cancer cells enhances the invasion and is
associated with the increased level of matrix metalloproteinase-2 and -9
expression.
AB - Claudin-4 is a member of a large family of transmembrane proteins known as
claudins, which are essential for the formation and maintenance of tight
junctions. Our previous studies have revealed that claudin-4 proteins are
overexpressed in metastatic gastric cancer. To clarify the roles of claudin-4 in
gastric cancer metastasis, human gastric adenocarcinoma (AGS) cells
constitutively expressing wild-type claudin-4 were generated. Expression of
claudin-4 in AGS cells was found to increase cell invasion and migration, as
measured by Boyden invasion chamber assays. Moreover, the claudin-4-expressing
AGS cells were found to have increased matrix metalloproteinase (MMP)-2 and -9
expression, indicating that claudin-mediated increased invasion may be mediated
through the activation of the MMP protein. Overall, the results suggest that
claudin-4 overexpression may promote gastric cancer metastasis through the
increased invasion of gastric cancer cells.
PMID- 25120726
TI - Combined treatment of PC-3 cells with ultrasound and microbubbles suppresses
invasion and migration.
AB - The aim of the present study was to investigate whether ultrasound treatment
combined with microbubbles inhibits cell invasion and migration in androgen
independent prostate cancer (PCa) cells and to identify the probable mechanism.
Ultrasound was used in continuous wave mode at a frequency of 21 kHz and with a
spatial-average temporal-average intensity of 46 mW/cm2. Ultrasound combined with
microbubbles (200 MUl; SonoVue) was administered to androgen-independent human
PCa PC-3 cells for 30 sec. The PC-3 cells were divided into three groups: The
control group, the ultrasound group (US) and the ultrasound combined with
microbubbles group (US + MB). Following treatment for 12, 24, 48 and 72 h, cell
counting kit-8 was used to assess cell viability. Cell invasion and migration was
measured 12 h after treatment using Transwell migration assays. Quantitative
polymerase chain reaction and western blot analysis were used to evaluate the
expression of the migration-associated proteins, matrix metalloproteinase (MMP)-2
and MMP-9. Cell reproduction levels in the US and US + MB groups were
significantly suppressed when compared with the control group (P<0.01) following
24 h of treatment and this suppression was significantly higher in the US + MB
group than in the US group (P<0.01). However, no significant differences in cell
reproduction levels between the three groups were identified at 12 h (P>0.05).
Ultrasound combined with microbubbles significantly suppressed the level of
invasion and migration in the PC-3 cells compared with the control group
(190.83+/-14.63 vs. 509.67+/-18.62, P<0.01; and 86.67+/-10.60 vs. 271.33+/-65.14;
P<0.01, respectively). Furthermore, combined treatment with ultrasound and
microbubbles suppressed the expression of MMP-2 and MMP-9. In conclusion, it was
found that ultrasound combined with microbubbles suppressed invasion and
migration in human PCa PC-3 cells via downregulation of MMP-2 and MMP-9.
PMID- 25120727
TI - Giant colonic lipoma with prolapse through the rectum treated by external local
excision: A case report.
AB - Colonic lipomas are a rare type of gastrointestinal benign tumor. Those that are
<2 cm are generally asymptomatic and do not require any treatment. However, those
that are >2 cm may be symptomatic, resulting in abdominal pain, changes in bowel
habits, intestinal obstruction and rectal bleeding. A 39-year-old male patient
presented with a mass prolapse through the anal canal, which was causing anal
pain and rectal bleeding. The patient was admitted to hospital via the emergency
services and directed to the Department of General Surgery with the preliminary
diagnosis of a rectal prolapse. A pedunculated polyp (size, 10*8*7.5 cm) was
detected at the 35th cm of the anal canal. Due to the large size of the polyp, an
endoscopic polypectomy could not be performed. Therefore, the prolapsed lipoma
was excised externally and the patient was discharged on the first postoperative
day on which no complications were experienced. A colonic lipoma must be
considered during the differential diagnosis of anorectal diseases, such as
hemorrhoids and rectal prolapses. Local excision, hemicolectomy, and segmental
and external resection should be considered in addition to an endoscopic
polypectomy for the diagnosis and treatment of colonic lipomas.
PMID- 25120728
TI - Intraspinal leiomyoma: A case report and literature review.
AB - Leiomyomas are benign tumors which are predominantly found in the genitourinary
and gastrointestinal tracts. Leiomyomas in the spine are extremely rare. The
current study presents a case of a 35-year-old female with intraspinal leiomyoma
who presented with low back pain and weakness in the left leg of two months.
Computerized tomography and magnetic resonance imaging revealed an epidural mass
at the T11-12 levels. The patient underwent a T11-12 laminectomy through
posterior approach, achieving total removal of the tumor with a well-demarcated
dissection plane. Pathological examination demonstrated a leiomyoma.
Postoperatively, the patient showed a significant improvement in neurological
function. Although intraspinal leiomyoma is extremely rare, it should be
considered in the differential diagnosis of spinal lesions in females. The
diagnosis is predominantly dependent on a pathological examination. Gross total
resection is recommended for its treatment, however the prognosis remains poor.
Post-operative hormonal therapy may be useful in controlling tumor recurrence.
PMID- 25120729
TI - Is apolipoprotein E4 an important risk factor for vascular dementia?
AB - Despite the fact that vascular dementia (VaD) represents the seconding leading
cause of dementia in the USA, behind only Alzheimer's disease (AD), there remains
a lack of consensus on the pathological criteria required for diagnosis of this
disease. A number of clinical diagnostic criteria exist but are poorly validated
and inconsistently applied. It is clear that vascular risk factors play an
important role in the etiology of VaD, including hypertension, stroke, diabetes,
and atherosclerosis. Vascular risk factors may increase the risk for VaD by
promoting inflammation, cerebral vascular disease, white matter lesions, and
hippocampal sclerosis. Because vascular risk factors seem to impart a high degree
of risk for conferring VaD, it seems logical that the apolipoprotein E (APOE)
status of individuals may be important. APOE plays a critical role in
transporting cholesterol in and out of the CNS and in AD it is known that
harboring the APOE allele increases the risk of AD perhaps due to the improper
functioning of this protein. The purpose of this review is to examine the
important pathological features and risk factors for VaD and to provide a
critical assessment of the current literature regarding whether or not apoE4 also
confers disease risk in VaD. The preponderance of data suggests that harboring
one or both APOE4 alleles elevates the risk for VaD, but not to the same extent
as found in AD.
PMID- 25120730
TI - A focused review of hematopoietic neoplasms occurring in the therapy-related
setting.
AB - Hematological neoplasms developed in patients with a history of cytotoxic
therapies comprise a group of diseases with a poor clinical outcome, and
collectively categorized as "therapy-related myeloid neoplasms" (t-MN) in the
2008 World Health Organization (WHO) Classification. In recent years, numerous
publications have emerged, and these studies have greatly expanded the scope of
our understanding in this field. We here focused our review on several selected
areas including secondary malignancies occurring in patients with autoimmune
diseases; radiation therapy alone as a causative agent; the similarity and
differences between therapy-related myelodysplastic syndromes (t-MDS) and acute
myeloid leukemia (t-AML); clinical behavior and treatment outcome of t-AML
patients with favorable cytogenetics; the incidence and clinical features of
myelodysplastic/myeloproliferative neoplasms, as well as acute lymphoblastic
leukemia and myeloproliferative neoplasms in patients with prior cytotoxic
exposure. These recent studies have shown that therapy-related hematopoietic
neoplasms are heterogeneous, and may manifest in various forms, more complex than
we have recognized previously. Cytogenetic abnormalities and underlying mutations
are likely to be the major factors dictating prognosis.
PMID- 25120732
TI - BMP-7 attenuates liver fibrosis via regulation of epidermal growth factor
receptor.
AB - The aim of this study was to elucidate the effect of bone morphogenetic protein-7
(BMP-7) on liver fibrosis induced by carbon tetrachloride (CCl4) in vivo and on
the hepatic stellate cells (HSC) activation in vitro. In vivo, thirty male ICR
mice were randomly allocated to three groups, the control group (n = 6), the CCl4
group (n = 18) and the BMP-7+CCl4 group (n = 6). The model of liver fibrosis was
induced by intraperitoneal injection with CCl4 three times per week lasting for
12 weeks in CCl4 group and the BMP-7+CCl4 group. After 8 weeks injection with
CCl4, mice were intraperitoneal injected with human recombinant BMP-7 in BMP
7+CCl4 group. Meanwhile, mice in the CCl4 group were only intraperitoneal
injection with equal amount of saline. The degree of liver fibrosis was assessed
by HE and Masson's staining. PCR and western blot were used to detect mRNA and
protein levels. In BMP-7+CCl4 group, serum levels of alanine aminotransferase
(ALT) and aminotransferase (AST) were decreased and serum albumin (Alb) was
increased. Meanwhile, the expressions of transforming growth factor-beta1 (TGF
beta1) and alpha-smooth muscle actin (alpha-SMA) were down-regulated by BMP-7
intervention as compared to the CCl4 group (P < 0.05). Furthermore, BMP-7 also
suppressed the expression of epidermal growth factor receptor (EGFR) and
phosphorylated-epidermal growth factor receptor (pEGFR). HE and Masson stain
showed that liver damage was alleviated in BMP-7+CCl4 group. In vitro study,
expression of EGFR, TGF-beta1 and alpha-SMA were down regulated by BMP-7 dose
dependently, indicating it might effect on suppression of HSC activation.
Therefore, our data indicate BMP-7 was capable of inhibiting liver fibrosis and
suppressing HSCs activation, and these effects might rely on its crosstalk with
EGFR and TGF-beta1. We suggest that BMP-7 may be a potential reagentfor the
prevention and treatment of liver fibrosis.
PMID- 25120731
TI - Omega-conotoxin MVIIC attenuates neuronal apoptosis in vitro and improves
significant recovery after spinal cord injury in vivo in rats.
AB - Excessive accumulation of intracellular calcium is the most critical step after
spinal cord injury (SCI). Reducing the calcium influx should result in a better
recovery from SCI. Calcium channel blockers have been shown a great potential in
reducing brain and spinal cord injury. In this study, we first tested the
neuroprotective effect of MVIIC on slices of spinal cord subjected to ischemia
evaluating cell death and caspase-3 activation. Thereafter, we evaluated the
efficacy of MVIIC in ameliorating damage following SCI in rats, for the first
time in vivo. The spinal cord slices subjected a pretreatment with MVIIC showed a
cell protection with a reduction of dead cells in 24.34% and of caspase-3
specific protease activation. In the in vivo experiment, Wistar rats were
subjected to extradural compression of the spinal cord at the T12 vertebral level
using a weigh of 70 g/cm, following intralesional treatment with either placebo
or MVIIC in different doses (15, 30 and 60 pmol) five minutes after injury.
Behavioral testing of hindlimb function was done using the Basso Beattie
Bresnahan locomotor rating scale, and revealed significant recovery with 15 pmol
(G15) compared to other trauma groups. Also, histological bladder structural
revealed significant outcome in G15, with no morphological alterations, and anti
NeuN and TUNEL staining showed that G15 provided neuron preservation and
indicated that this group had fewer neuron cell death, similar to sham. These
results showed the neuroprotective effects of MVIIC in in vitro and in vivo model
of SCI with neuronal integrity, bladder and behavioral improvements.
PMID- 25120733
TI - Benign notochordal cell tumor: a retrospective study of 11 cases with 13 vertebra
bodies.
AB - PURPOSE: To analyze the clinical data, MRI, pathological diagnosis, treatment and
long-term effects of benign notochordal cell tumor (BNCT), a newly described
novel spine tumor. METHODS: We retrospectively studied 11 patients' clinical data
of the above. RESULTS: The ratio of males to females was 4:7, and the average age
was 49.2 years (range, 18-74 years). Cervical vertebra (5; 38.5%) and thoracic
vertebra (5; 38.5%) were the most frequent site followed by the lumbar vertebra
(3; 23%). Pain was the main symptom except case 2 who were diagnosed accidently
because of prostate cancer. The mean delay from first clinical symptoms to
diagnosis was ranged from 2 months to 20 years. MRI showed all BNCTs were
osteolytic lesions with hypointense on T1-weighted sequences, hyperintense on T2
weighted sequences. There were 4 vertebral bodies with wedge fracture. There were
two cases that had two noncontiguous vertebral bodies with BNCT. In histology,
marrow replacement was noted by multivacuolated physaliphorous cells
immunoreactive for CK, EMA and S100 protein. All 10 cases except case 2 had
vertebral reconstruction and fixation with different methods. Of the 11 patients,
9 had full follow-up data which showed no evidence of recurrence or metastasis
without further treatment. CONCLUSION: Noncontiguous multi-centricity BNCTs are
rare. No specific vertebrae are more frequently involved. Once BNCT is diagnosed
by pathology, the surgical intervention is necessary for the patients with
obvious clinical symptoms although it is benign. There is no evidence of BNCT
recurrence or metastasis.
PMID- 25120734
TI - Primary angiosarcoma of the kidney: case analysis and literature review.
AB - OBJECTIVE: To study the clinical presentation, diagnosis, treatment and prognosis
of primary angiosarcoma of the kidney. METHODS: We treated a patient with primary
angiosarcoma, then searched the published papers with the terms of 'primary
angiosarcoma of the kidney' and 'primary renal angiosarcoma' in PubMed database,
found 27 patients with detailed data, and analyzed their characters in the
clinical presentation, diagnosis, treatment and prognosis. RESULTS: The primary
angiosarcoma occurred mainly from 50 years old to 69 years old, predominated in
male patients. The clinical presentation was flank pain and hematuria, and the
nephrectomy was the mainstay of the treatment; the maximum diameter and the
metastasis status at the time of diagnosis had important prognostic value.
CONCLUSIONS: The primary angiosarcoma is a rare carcinoma and lacks of specific
presentation. Accurate diagnosis depends on pathological examination. Surgery is
the mainstay of the treatment, but the prognosis is poor.
PMID- 25120735
TI - Immune cells in primary and metastatic gastrointestinal stromal tumors (GIST).
AB - We have previously described immune cells in untreated primary gastrointestinal
stromal tumors (GIST). Here we compare immune cells in metastatic and primary
GIST, and describe their chemoattractants. For this purpose, tissue microarrays
from 196 patients, 188 primary and 51 metastasized GIST were constructed for
paraffin staining. Quantitative analysis was performed for cells of macrophage
lineage (Ki-M1P, CD68), T-cells (CD3, CD56) and B-cells (CD20). Chemokine gene
expression was evaluated by real-time RT-PCR. Immuno-localisation was verified by
immunofluorescence. Ki-M1P+ cells were the predominant immune cells in both
primary and metastatic GIST (2 8.8% +/- 7.1, vs. 26.7% +/- 6.3). CD68+
macrophages were significantly fewer, with no significant difference between
primary GIST (3.6% +/- 2.1) and metastases (4.6% +/- 1.5). CD3+ T-cells were the
most dominant lymphocytes with a significant increase in metastases (7.3% +/- 2.3
vs. 2.2% +/- 1.8 in primary GIST, P < 0.01). The percentage of CD56+ NK-cells was
1.1% +/- 0.9 in the primary, and 2.4 +/- 0.7 (P < 0.05) in the metastases. The
number of CD20+ B-cells was generally low with 0.6% +/- 0.7 in the primary and
1.8% +/- 0.3 (P < 0.05) in the metastases. Analysis of the metastases showed
significantly more Ki-M1P+ cells in peritoneal metastases (31.8% +/- 7.4 vs.
18.2% +/- 3.7, P < 0.01), whilst CD3+ T-cells were more common in liver
metastases (11.7% +/- 1.8 vs. 4.4% +/- 2.6, P < 0.01). The highest transcript
expression was seen for monocyte chemotactic protein 1 (MCP1/CCL2), macrophage
inflammatory protein 1alpha (MIP-1alpha/CCL3) and the pro-angiogenic growth
related oncoprotein 1 (Gro-alpha/CXCL-1). Whilst the ligands were predominantly
expressed in tumor cells, their receptors were mostly present in immune cells.
This locally specific microenvironment might influence neoplastic progression of
GIST at the different metastatic sites.
PMID- 25120736
TI - Angiopoietin-1 gene-modified human mesenchymal stem cells promote angiogenesis
and reduce acute pancreatitis in rats.
AB - Mesenchymal stem cells (MSCs) can serve as a vehicle for gene therapy.
Angiopoietin-1 (ANGPT1) plays an important role in the regulation of endothelial
cell survival, vascular stabilization, and angiogenesis. We hypothesized that
ANGPT1 gene-modified MSCs might be a potential therapeutic approach for severe
acute pancreatitis (SAP) in rats. Human umbilical cord-derived MSCs with or
without transfection with lentiviral vectors containing the ANGPT1 gene were
delivered through the tail vein of rats 12 h after induction of SAP.
Administration of MSCs alone significantly reduced pancreatic injury and
inflammation, as reflected by reductions in pancreatitis severity scores and
serum amylase and lipase levels as well as reducing the serum levels of
proinflammatory cytokines (TNF-alpha, IFN-gamma, IL-1beta, and IL-6).
Furthermore, administration of ANGPT1-transfected MSCs resulted in not only
further reductions in pancreatic injury and serum levels of proinflammatory
cytokines, but also promotion of pancreatic angiogenesis. These results suggest
that MSCs and ANGPT1 have a synergistic role in the treatment of SAP. ANGPT1 gene
modified MSCs may be developed as a potential novel therapy strategy for the
treatment of SAP.
PMID- 25120737
TI - Mast cell chymase in keloid induces profibrotic response via transforming growth
factor-beta1/Smad activation in keloid fibroblasts.
AB - This study was to examine whether mast cell chymase exists in human keloids and
exerts its profibrotic effect via transforming growth factor-beta1/Smad signaling
pathway. The number of mast cells and the expression levels of chymase in keloids
and normal skin were examined by immunohistochemistry assays. The mRNA expression
and activity changes of chymase in keloids and normal skin were determined by
real-time quantitative PCR and radioimmunoassay. After keloid fibroblasts were
treated with different concentrations of chymase (0, 15, 30, 60, and 120 ng/mL)
for various time periods, the proliferation of keloid fibroblasts, collagen
synthesis, mRNA and protein expression of TGF-beta1, and the protein expression
of phosphorylated Smad2/3, Smad2/3 and Smad7 were investigated using MTT assay,
ELISA and Western blotting. Mast cells and chymase exist in keloid. Gene
expression and activity of mast cell chymase in keloid are significantly higher
than those in normal skin. Chymase promotes keloid fibroblast proliferation and
collagen synthesis by activating TGF-beta1. The activation of Smad protein
signaling pathway by chymase is related to the elevated P-Smad protein expression
in keloid fibroblasts. Our data demonstrated that mast cell chymase plays an
important role in keloid formation through TGF-beta1/Smad signaling pathway.
PMID- 25120738
TI - Generation of a chimeric dust mite hypoallergen using DNA shuffling for
application in allergen-specific immunotherapy.
AB - Specific immunotherapy (SIT) is the only treatment that provides long lasting
relief of allergy symptoms. Unfortunately, SIT-based traditional remedies carry
the risk of producing local and/or systemic side effects. To improve the safety
and efficacy of SIT, it has been proposed that SIT must utilize allergens that
are hypoallergenic but hyperimmunogenic. Therefore, we used DNA shuffling to
generate mutant genes encoding hypoallergens with potent immunogenicity and
screened them for their capacity to modify the allergic response. We tentatively
shuffled the major group 1 allergen genes from house dust mite, Dermatophagoides
farinae and Dermatophagoides pteronyssinus, and discovered a novel chimeric gene,
termed C 1. The gene was expressed in Escherichia coli (E. coli) and the chimeric
protein C 1 was purified. An animal model of asthma demonstrated that C 1 not
only decreased the production of serum IgE and IgG1, and inhibited the production
of IL-4 and IL-5 in the bronchoalveolar lavage fluid (BALF). C 1 also boosted the
levels of IgG2a and IFN-gamma, which may demonstrate a rebalance of TH1 and TH2
allergic response. Additionally, flow cytometry showed that the immunogenicity of
C 1 was higher than that of ProDer f 1, but was not significantly different from
that of ProDer p 1. Our findings suggest that the C 1 is hypoallergenic and yet
highly immunogenic, which makes it potentially safe and effective for use in SIT
of allergic asthma.
PMID- 25120739
TI - Interleukin-1beta induces autophagy by affecting calcium homeostasis and
trypsinogen activation in pancreatic acinar cells.
AB - The strong up-regulation of inflammatory mediators has been reported to play a
key role in acute pancreatitis (AP). Elevated serum levels of interleukin-1beta
(IL-1beta) are associated with the development of AP. However, the precise effect
and mechanism of IL-1beta in AP remains obscure. In this study, we investigated
the potential role and mechanism of IL-1beta in AP. We measured autophagy
activation in response to IL-1beta in AR42J cells. The disrupting effects of IL
1beta on cellular Ca(2+) were observed. To determine whether the disruption of
Ca(2+) signaling has protective effects in vivo during AP, male C57BL/6 mice were
treated with cerulein to induce AP. We found that the treatment of AR42J cells
with IL-1beta triggered autophagy and that the autophagic flux was impaired. In
addition, IL-1beta induced Ca(2+) release from the ER. Furthermore, the
expression of the ER stress markers GRP78 and IRE1 also increased. 2APB, an
antagonist of the InsP3 receptor, inhibited increased expression of autophagy
markers. Subsequent biochemical assays revealed that co-culture with IL-1beta
could induce the activation of trypsinogen to trypsin and reduce the viability of
acinar cells. Pathological changes of the pancreas were also observed in vivo. We
found that the pathological injuries of the pancreas were significantly
alleviated in mice co-treated with 2APB. Taken together, our results indicate
that IL-1beta can induce trypsin activation and decrease cellular viability in
pancreatic acinar cells. These effects depend on impaired autophagy via
intracellular calcium changes. Ca(2+) signaling may become a promising
therapeutic target in the treatment of pancreatitis.
PMID- 25120740
TI - Prognostic value of CD44 expression in non-small cell lung cancer: a systematic
review.
AB - BACKGROUND: CD44 is a potentially interesting prognostic marker and therapeutic
target in non-small cell lung cancer (NSCLC). Although the expression of CD44 has
been reported to correlate with poor prognosis of NSCLC in most literatures, some
controversies still exist. Since the limited patient numbers within independent
studies, here we performed a meta-analysis to clarify the correlations between
CD44 expression and prognosis and clinicopathological features in NSCLC. METHODS:
Relevant literatures were identified using PubMed, EMBASE and CNKI (China
National Knowledge Infrastructure) databases (up to February 2014). Data from
eligible studies were extracted and included into meta-analysis using a random
effects model. Studies were pooled. Summary hazard ratios (HR) and clinical
parameters were calculated. RESULTS: We performed a final analysis of 1772
patients from 23 evaluable studies for Prognostic Value and 2167 patients from 28
evaluable studies for clinicopathological features. Our study shows that the
pooled hazard ratio (HR) of overexpression CD44-V6 for overall survival in NSCLC
was 1.63 [95% confidence interval (CI): 1.20-2.21] by univariate analysis and
1.29 (95% CI: 0.71-2.37) by multivariate analysis.The pooled HR of overexprssion
panCD44 for overall survival in NSCLC was 1.53 (95% CI: 0.58-4.04) by univariate
analysis and 3.00 (95% CI: 1.53-5.87) by multivariate analysis. Overexpression of
CD44-V6 is associated with tumor differentiation (poor differentiation, OR =
1.66, 95% CI: 1.12-2.45), tumor histological type [squamous cell carcinomas
(SCC), OR = 2.6, 95% CI: 1.63-5.02], clinical TMN stage (TMN stage III, OR =
2.22, 95% CI: 1.44-3.43) and lymph node metastasis (N1-3, 3.52, 95% CI: 2.08
5.93) in patients with NSCLC. However, there was no significant association
between CD44-V6 and tumor size [T category, OR = 1.42, 95% CI: 0.73-2.78].
CONCLUSION: Our meta-analysis showed that CD44-V6 is an efficient prognostic
factor for NSCLC. Overexpression of CD44-V6 was significantly associated with
tumor differentiation, tumor histological type, clinical TMN stage and lymph node
metastasis. However, there was no significant association between CD44-V6 and
tumor size. Large prospective studies are now needed to confirm the clinical
utility of CD44 as an independent prognostic marker.
PMID- 25120741
TI - Efficacy of glucocorticoids in rodents of severe acute pancreatitis: a meta
analysis.
AB - BACKGROUND: The use of corticosteroid in the management of severe acute
pancreatitis (SAP) remains contentious and is still being debated despite many
pre-clinical studies demonstrating benefits. The limitations of clinical research
on corticosteroid in SAP are disparities with regard to benefit, a lack of
adequate safety data and insufficient understanding of its mechanisms of action.
Thus, we performed a meta-analysis to assess the effectiveness of corticosteroid
in experimental SAP and take a closer look at the relation between the animal
studies and prospective trials. METHODS: Studies investigating corticosteroid use
in rodent animal models of SAP were identified by searching multiple three
electronic databases through October 2013, and by reviewing references lists of
obtained articles. Data on mortality, changes of ascitic fluid and histopathology
of pancreas were extracted. A random-effects model was used to compute the pooled
efficacy. Publication bias and sensitivity analysis were also performed. RESULTS:
We identified 15 published papers which met our inclusion criteria.
Corticosteroid prolonged survival by a factor of 0.35 (95% CI 0.21-0.59).
Prophylactic use of corticosteroid showed efficacy with regards to ascitic fluid
and histopathology of pancreas, whereas therapeutic use did not. Efficacy was
higher in large dose and dexamethasone groups. Study characteristics, namely type
of steroids, rout of delivery, genders and strains of animal, accounted for a
significant proportion of between-study heterogeneity. No significant publication
bias was observed. CONCLUSIONS: On the whole, corticosteroids have showed
beneficial effects in rodent animal models of SAP. Prophylactic use of
corticosteroid has failed to validate usefulness in prophylaxis of postendoscopic
retrogradcholangiopancreatography pancreatitis. Further appropriate and
informative animal experiments should be performed before conducting clinical
trials investigating therapeutic use in SAP.
PMID- 25120742
TI - In vitro differentiation of bone marrow mesenchymal stem cells into endometrial
epithelial cells in mouse: a proteomic analysis.
AB - OBJECTIVE: Mouse bone marrow mesenchymal stem cells (BMSCs) have been
demonstrated to differentiate into female endometrial epithelial cells (EECs) in
vivo. Our previous studies demonstrated that BMSCs can differentiate in the
direction of EECs when co-cultured with endometrial stromal cells in vitro. Here,
we obtain and analyse differential proteins and their relevant pathways in the
process of BMSCs differentiating into EECs by isobaric tags for relative and
absolute quantitation (iTRAQ) proteomic analysis. METHODS: A 0.4-MUm pore size
indirect co-culture system was established with female mice endometrial stromal
cells (EStCs) restricted in the upper Transwell chamber and BMSCs in the lower
well plate. After indirect co-culture for several days, the BMSCs were revealed
to progressively differentiate towards EECs in vitro. Then, four groups were
divided according to different co-culture days with single culture groups of
BMSCs as controls. Proteins were detected using iTRAQ based on 2DLC-ESI-MS/MS and
data were analysed by bioinformatics. RESULTS: A total number of 311 proteins
were detected, of which 210 proteins were identified with relative quantitation.
Among them, 107 proteins were differentially expressed with a 1.2-fold change as
the benchmark, with 61 up-regulated and 46 down-regulated proteins. Differential
proteins CK19 and CK8 were epithelial markers and upregulated. Stromal marker
vimentin were downregulated. Top canonical pathways was "remodeling of epithelial
adhesions junctions" and "actin cytoskeleton signaling". Top networks was "cell
to-cell signaling and interaction, tissue development and cellular movement"
regulated by ERK/MAPK and alpha-catenin. CONCLUSION: To the best of our
knowledge, this is the first preliminary study of differential protein expression
in the differentiation process of BMSCs into EECs in vitro. We further elucidated
BMSCs differentiated in the direction of EECs. In addition, ERK/MAPK and alpha
catenin played important roles by regulating core differential proteins in the
"cell-to-cell signaling and interaction, tissue development and cellular
movement" network.
PMID- 25120743
TI - Recurrent inflammatory myofibroblastic tumors harboring PIK3CA and KIT mutations.
AB - Inflammatory myofibroblastic tumour (IMT) is a relatively rare soft tissue
malignancy. It exhibits locally aggressive behavior with a tendency for local
recurrence and rare metastasis, and rare recurrent IMTs may show histological
progression. The genetic hallmark of IMT is ALK rearrangement from chromosome arm
2p, but gene mutations involved in IMT remain poorly understood. The aim of the
present study was to perform a pairwise comparison of the gene mutations
occurring in primary and recurrent IMT from the same patient. We conducted a high
throughput analysis of 238 known mutations of 19 oncogenes in pairwise comparison
primary and recurrent samples from 2 patients of IMT using Sequenom MassARRAY
technology. Our results revealed 2 mutations in 2 recurrent lesion samples,
including one in exon 11 of the KIT gene, resulting in a T-C substitution at
position 1727 (L576P), the recurrent sample underwent histologic progression with
"pleomorphic undifferentiated sarcoma-like" transformation; the other mutation
was in exon 19 of the phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic
subunit alpha (PIK3CA) gene, resulting in a G-A substitution at position 1624
(E542K). Moreover, no any mutation was found in the primary lesion samples from 2
patients. Our findings suggest that variable genome changes might be present in
IMT, especially during the progression from a primary tumour to recurrence. To
the best of our knowledge, no such longitudinal study of IMT has been undertaken
previously.
PMID- 25120744
TI - Accuracy of fine needle aspiration biopsy processed by cytologic smear and cell
block techniques for the diagnosis of lacrimal gland tumors: a study of 48 cases.
AB - OBJECTIVE: To study the accuracy of fine needle aspiration biopsy (FNAB)
processed by smear cytology and cell block (CB) techniques for the diagnosis of
lacrimal gland tumors (LGTs). STUDY DESIGN: In a prospective study, we enrolled
48 consecutive patients with LGTs. Immediately after excision of LGTs, the
tissues were underwent FNAB with 23-gauge needles. The FNAB samples were
processed to produce cytologic smears and CB from which slides were cut for
immunohistochemical staining. The remainders were submitted for routine
histopathologic processing. The diagnostic value of FNAB was assessed by
comparing the FNAB diagnoses to those made by routine histopathology. RESULTS:
Cytopathologic evaluations based on smear cytology and CB with sections stained
immunohistochemically can distinguish non-epithelial lesions from epithelial ones
in all cases. The diagnostic sensitivities, specificities, and accuracies for
distinguishing benign from malignant lesions were: cytologic smears--76%, 68%,
and 71%, respectively; CB with immunohistochemical staining--88%, 87%, and 88%,
respectively. The accuracy of the tissue diagnosis compared to routine
histopathology was less for cytologic smears (58%) than for CB with
immunohistochemistry (81%; P < 0.05). CONCLUSIONS: FNAB of LGT processed using a
CB technique capable of producing immunohistochemically stained slides results in
a greater percentage of accurate tissue diagnoses than do cytologic smears, when
compared to routine histopathology.
PMID- 25120745
TI - IL-22 promotes the migration and invasion of gastric cancer cells via IL
22R1/AKT/MMP-9 signaling.
AB - IL-22, one important inflammatory cytokine of the IL-10 family, exerts its
functions via IL-22 receptor that is composed of IL-22R1 and IL-10R2 subunits.
Although IL-22 expression is reported to be elevated in many cancers, and
increased IL-22 expression correlates with tumor progression and poor prognosis,
little is known about the role of IL-22 in gastric cancer. In our study, we found
that IL-22 stimulation promoted the migration and invasion of SGC-7901 cells.
Furthermore, IL-22 increased AKT activation and MMP-9 production in a time- and
dose-dependent manner, while knockdown of IL-22R1 attenuated the effect of IL-22
on gastric cancer cells. In addition, blocking of AKT activation suppressed the
expression and secretion of MMP-9. Taken together, this present study suggests
that IL-22 stimulation enhances the migration and invasion of gastric cancer
cells by regulating IL-22R1/AKT/MMP-9 signaling axis.
PMID- 25120746
TI - Monoacylglycerol lipase promotes metastases in nasopharyngeal carcinoma.
AB - Monoacylglycerol lipase (MAGL) is a serine hydrolase that hydrolyzes
monoacylglycerides into free fatty acids and glycerol. It has recently been found
to be involved in cancer progression through the free fatty acid or
endocannabinoid network after studies on its function in the endocannabinoid
system. Here, we determined a role for MAGL in nasopharyngeal carcinoma (NPC),
which is known for its high metastatic potential. Among the different NPC cells
we tested, MAGL was highly expressed in high metastatic NPC cells, whereas low
metastatic potential NPC cells exhibited lower expression of MAGL. Overexpression
of MAGL in low metastatic NPC cells enhanced their motile behavior and metastatic
capacity in vivo. Conversely, knockdown of MAGL reduced the motility of highly
metastatic cells, reducing their metastatic capacity in vivo. Growth rate was not
influenced by MAGL in either high or low metastatic cells. MAGL expression was
associated with the epithelial-mesenchymal transition (EMT) proteins, such as E
cadherin, vimentin and Snail. It was also related to the sidepopulation (SP) of
NPC cells. Our findings establish that MAGL promotes metastases in NPC through
EMT, and it may serve as a target for the prevention of NPC metastases.
PMID- 25120747
TI - Transplanted bone marrow mesenchymal stem cells protects myocardium by regulating
14-3-3 protein in a rat model of diabetic cardiomyopathy.
AB - OBJECTIVE: This study examined the mechanism of bone marrow mesenchymal stem
cells (BMSCs) up-regulating the expression of 14-3-3 protein, blocking the
myocardial apoptosis in diabetic cardiomyopathy and thereby improving cardiac
function. METHODS AND RESULTS: (1) Rat model of diabetic cardiomyopathy was made
by feeding rats with high fat/high sugar diet and intraperitoneal injection of
small dose of streptozocin (STZ). The model was successfully established as
confirmed by the detection of blood sugar, lipid profile, ultrasonographic and
hemodynamic examinations. (2) Bone marrow (BM) liquid was taken from the rat
femur and tibia bones. The BMSCs were obtained by culture and were confirmed by
phase-contrast microscopy and flow cytometry. The BMSCs were transplanted into
the rats and fluorescent microscopy showed that transplantation was successful.
(3) TUNNEL, Western blotting revealed that in rats of DCM group, myocardial
apoptosis was more severe and expression of capase-3 was significantly up
regulated while in rats receiving transplantation of BMSCs showed opposite
changes, with the differences being statistically significant (P < 0.05). (4)
Western blotting exhibited that, compared with DCM group, 14-3-3 and p-Ask1
protein was significantly increased while Ask1 was obviously decreased.
CONCLUSION: Our findings suggested that transplantation of bone marrow
mesenchymal stem cells could inhibit the myocardial apoptosis in diabetic
cardiomyopathy, possibly by up-regulating the expression of 14-3-3 protein and
inhibiting the phosphorylation of Ask1.
PMID- 25120748
TI - Co-expression of delta-catenin and RhoA is significantly associated with a
malignant lung cancer phenotype.
AB - Delta-catenin, a member of the p120-catenin subfamily, and the Rho GTPase RhoA
both have roles in the regulation of the cytoskeleton. In this study, we found
that delta-catenin positive expression and RhoA over-expression is consistently
found in non-small cell lung cancer, but not in normal lung tissue, and that
their co-expression was significantly associated with histological type,
differentiation, pTNM stage, lymphatic metastasis and a poor prognosis. We also
demonstrate that delta-catenin can directly interact with RhoA and regulate its
activity, which in turn mediates tumor invasion and metastasis.
PMID- 25120749
TI - Capsular tension ring implantation after lens extraction for management of
subluxated cataracts.
AB - PURPOSE: To evaluate the safety and efficacy of implantation of a capsular
tension ring (CTR) and posterior chamber intraocular lens (PCIOL) after lens
extraction in subluxated cataracts. SETTING: Department of Ophthalmology,General
Hospital of PLA, Beijing, China. DESIGN: Prospective case series. METHODS: We
selected 36 eyes in 34 patients with zonular dialysis <150 degrees . After
emulsification and removal of the residual cortex, we inserted a CTR into the
capsular bag to center the PCIOL. We measured preoperative and postoperative best
corrected visual acuity (BCVA), centration of the CTR and IOL, and perioperative
complications. RESULTS: No capsule collapseor fluctuationof the anterior chamber
occurred. Most eyes (63.89%) had nuclear sclerosis of >= 3+. A CTR was implanted
into the capsular bag without extension of zonular dialysis. A traumatic
subluxated cataract was the most common cause (20 of 36 [55.56%]). We found a
subluxated cataract in 3 eyes (3 of 36 [8.33%]) with previous acute angle-closure
glaucoma. Mean follow up was 20.3 +/- 2.4 months. Preoperatively, only 5 eyes
(13.89%) had a BCVA of >= 20/40, compared with 30eyes at the last visit (83.33%,
P<.001). Improved BCVA was achieved in 33 eyes (91.7%) in week 1, and visual
acuity remained stable up to 1 year. The CTRs with PCIOL were well centered at 1
year. CONCLUSION: In patients with a subluxated hard cataract <120 degrees , CTR
implantation should be performed after lens extraction without extension of
zonular dialysis and capsular destabilization. Maintaining anterior chamber depth
and avoiding capsular bag collapse are critical.
PMID- 25120750
TI - Clinical value of CD133 and nestin in patients with glioma: a population-based
study.
AB - Cancer stem cell-related (CSC) markers have been suggested to have promising
potentials as novel types of prognostic and predictive markers in gliomas.
However no single CSC-related marker is currently used in clinical decisions. The
aim of this study was to investigate the prognostic value of CD133 and nestin
separately and in combination using a novel quantitative approach in a well
characterized population-based cohort of glioma patients. The expression of CD133
and nestin was measured by systematic random sampling in stained paraffin
sections from 239 glioma patients diagnosed between 2005 and 2009. We found that
the expression of CD133 did not correlate with WHO grade, and there was no
association with overall survival (OS). The level of nestin correlated positively
with WHO grade. In patients with WHO grade II tumors, a high level of nestin was
associated with short progression-free survival (PFS) in multivariate analysis.
High levels of co-localization were associated with poor PFS in patients with WHO
grade II tumors, but not with OS. We conclude that CD133 was not an independent
prognostic factor, but a high level of nestin was associated with poor PFS in
patients with WHO grade II tumors. The combination of double-immunofluorescence
and automated analysis seems to be a feasible and reproducible approach for
investigation of the prognostic potential of biomarkers.
PMID- 25120751
TI - Expression of leucine aminopeptidase 3 (LAP3) correlates with prognosis and
malignant development of human hepatocellular carcinoma (HCC).
AB - Leucine aminopeptidases (LAPs) were associated with tumor cell proliferation,
invasion and/or angiogenesis. LAP3 is one important member of this family.
However, its clinical significance and biological function in hepatocellular
carcinoma (HCC) remains unknown. In the present study, we demonstrated that LAP3
expression was significantly up-regulated in HCC tissues as well as cells and was
closely correlated with lower differentiation, positive lymph node metastasis and
high Ki-67 expression, indicating a poor prognosis. Then cell viability assays,
flow cytometry assays, wound-healing assays and matrigel invasion assays were
performed to demonstrate that LAP3 promoted HCC cells proliferation by regulating
G1/S checkpoint in cell cycle and advanced HCC cells migration. Furthermore, we
discovered that knockdown LAP3 will enhance the sensitivity of HCC cells to
cisplatin, thus promoting the cell death of HCC cells. Collectively, our results
indicated that up-regulated expression of LAP3 might contribute to the
proliferation and metastasis of HCC. Our data gains greater insight into the
cancer-promoting role of LAP3 and its functions in HCC cells, possibly providing
potential therapeutic strategies for clinical trials.
PMID- 25120753
TI - Co-expression of uPAR and CXCR4 promotes tumor growth and metastasis in small
cell lung cancer.
AB - Urokinase-type plasminogen activator receptor (uPAR) and C-X-C-chemokine receptor
4 (CXCR4) are considered as key molecules in invasion and metastasis of several
cancers via extracellular matrix degeneration and assist tumor metastasis to
specific sites by chemotaxis. However, the combined effect of uPAR and CXCR4 on
small cell lung cancer (SCLC), the most aggressive type of lung cancer, is not
clear. In this study, we detected the expression of uPAR and CXCR4 in SCLC tissue
samples (n = 50) by immunohistochemistry. The tumors with high expression of both
uPAR and CXCR4 (12/50) had larger size, higher lymph node (LN) metastasis and
worse prognosis of patients than those with low expression of uPAR and CXCR4
(38/50) (P < 0.05). We further identified and isolated the both uPAR and CXCR4
positive expression subpopulation cells (uPAR(+)CXCR4(+) cells) from the SCLC
cell line H446 by flow cytometry. The uPAR(+)CXCR4(+) cancer cells showed a
higher invasive and migrating capacity in the transwell and wound healing assays
compared with other subpopulation cells (P < 0.05). uPAR(+)CXCR4(+) cells
injected subcutaneously in nude mice markedly increased tumor growth and induced
lung metastasis, while other subpopulation cells did not. In conclusion, these
data suggest that uPAR and CXCR4 co-expression predicts worse prognosis of SCLC
patients. uPAR(+)CXCR4(+) cells promote the tumor growth and play a potential
role in metastasis of SCLC.
PMID- 25120754
TI - Effects of simulated microgravity by RCCS on the biological features of Candida
albicans.
AB - During the spaceflight, a wide variety of microorganisms may be carried to the
outer space by astronauts and aviation component. The yeast Candida albicans is
an important opportunistic pathogen responsible for a variety of cutaneous and
systemic human infections in human body, and the yeast cell itself could be
affected by various stressful environmental factors including the weightless
environment. We evaluated the effects of simulated microgravity on biological
features of Candida albicans using the rotary cell culture system (RCCS). The
growth curves of Candida albicans cultured in RCCS were recorded by
spectrophotometer, the morphogenic switches were observed by optical microscope,
and the viability of cells exposed to the various concentrations of fluconazole
solution was assayed by flow cytometry at 7th, 14th and 21st day of experiment.
The results showed that Candida albicans SC5314 under modeled microgravity were
manifested as the growth curves leftward-shifted, lag phase shortened, along with
logarithmic phase and stationary phase forwarded (P < 0.05). The simulated
microgravity increased the growth rate and mycelia formation of Candida albicans.
A statistically significant decrease in viability was detected in cells cultured
for 7 d, 14 d and 21 d in group of simulated microgravity compared with the
control group (P < 0.05). The increase of exposure time to simulate microgravity
resulted in the decrease of viability of cells accordingly in same drug
concentration compared with the control group. The study demonstrated that the
three weeks' simulated microgravity in RCCS had a noticeable affect on the growth
status of mycelia and spores and the morphogenic switches of Candida albicans,
meanwhile, the yeast cells under simulated microgravity showed an increased
antifungal susceptibility to fluconazole.
PMID- 25120752
TI - RNA-seq identifies determinants of oxaliplatin sensitivity in colorectal cancer
cell lines.
AB - Oxaliplatin-based chemotherapy, such as FOLFOX, is the first-line therapy for
advanced colorectal cancer (CRC) or metastatic CRC patients. However, the partial
response of patients to these regimes and the severe peripheral neuropathy
toxicity induced by oxaliplatin makes it urgent to figure out biomarkers for
oxaliplatin sensitivity to select suitable patients who benefit from these
treatments. In present work, 21 CRC cell lines with different sensitivities to
oxaliplatin were applied to RNA-seq. The basal expression profiles of these cell
lines were correlated to their response to oxaliplatin. Bioinformatics analysis
suggested that expression of 58 genes was correlated, negatively or positively,
to oxaliplatin response across the 21 CRC cell lines. These 58 genes were mainly
enriched in small molecules biochemistry, Wnt/beta-catenin signaling and EMT
pathways. The latter two pathways were predicted to be activated in oxaliplatin
resistant CRC cell lines. Moreover, 15 genes were validated by qPCR that their
expression levels were actually closely correlated to their response to
oxaliplatin, in line with the biocomputation prediction. Taken together, our work
might provide potential biomarkers for oxaliplatin sensitivity in CRC cell lines
and therapeutic targets for combinational therapy with oxaliplatin.
PMID- 25120755
TI - Aldo-keto reductase family 1 member B8 is secreted via non-classical pathway.
AB - Mouse aldo-keto reductase family 1 member B8 (AKR1B8) has the highest similarity
to human aldo-keto reductase family 1 member B10 (AKR1B10), a secretory protein
through lysosomes-mediated non-classical secretory pathway. To identify whether
AKR1B8 is secreted through the same pathway, we carried out this study. Self
developed sandwich ELISA and western blot were used to detect AKR1B8 in cells and
culture medium of CT-26 murine colon carcinoma cells. AKR1B8 releases in an
independent manner to Brefeldin A, an inhibitor of ER-to-Golgi classical
secretion pathway. Several factors, which are involved in the non-classical
secretion pathway, such as temperature, ATP and calcium ion, regulated AKR1B8
secretion from mouse colorectal cancer cells CT-26. Lysosomotropic NH4Cl
increased AKR1B8 secretion, and AKR1B8 was located in isolated lysosomes.
Therefore, AKR1B8 is a new secretory protein through the lysosomes-mediated non
classical pathway.
PMID- 25120756
TI - Evaluation of glycophenotype in prostatic neoplasm by chemiluminescent assay.
AB - This work aimed to evaluate the glycophenotype in normal prostate, bening
prostatic hyperplasia (BPH) and prostatic adenocarcinoma (PCa) tissues by a
chemiluminescent method. Concanavalin A (Con A), Ulex europaeus agglutinin (UEA
I) and Peanut agglutinin (PNA) lectins were conjugated to acridinium ester
(lectins-AE). These conjugates remained capable to recognize their specific
carbohydrates. Tissue samples were incubated with lectins-AE. The
chemiluminescence of the tissue-lectin-AE complex was expressed in relative light
units (RLU). Transformed tissues (0.25 cm(2) by 8 um of thickness) showed
statistical significant lower alpha-D-glucose/mannose (BPH: 226,931 +/- 17,436;
PCa: 239,520 +/- 12,398) and Gal-beta(1-3)-GalNAc (BPH: 28,754 +/- 2,157; PCa:
16,728 +/- 1,204) expression than normal tissues (367,566 +/- 48,550 and 409,289
+/- 22,336, respectively). However, higher alpha-L-fucose expression was observed
in PCa (251,118 +/- 14,193) in relation to normal (200,979 +/- 21,318) and BHP
(169,758 +/- 10,264) tissues. It was observed an expressive decreasing of the
values of RLU by inhibition of the interaction between tissues and lectins-AE
using their specific carbohydrates. The relationship between RLU and tissue area
showed a linear correlation for all lectin-AE in both transformed tissues. These
results indicated that the used method is an efficient tool for specific,
sensitive and quantitative analyses of prostatic glycophenotype.
PMID- 25120757
TI - Propranolol enhanced adipogenesis instead of induction of apoptosis of
hemangiomas stem cells.
AB - Propranolol has been widely used in treating infantile hemangiomas (IHs). But
recurrence of IHs was found in some cases on cessation of propranolol treatment.
The other is that Chinese individuals reacted to propranolol differently from
American Whites. Whether the difference of sensitivity is due to the beta
adrenoceptor (beta-AR) expression pattern of hemangioma initiating cells remains
unclear. In the present study, we isolated hemangioma-derived stem cells (hemSCs)
from proliferative IHs and analyzed the biological characteristics and beta-AR
expression pattern of hemSCs by immunostaining, Western blotting and multilineage
differentiation assay as well. We also tested the effects of propranolol on
hemSCs by evaluating VEGF expression, proliferation and apoptosis related
parameters. Our results indicated that CD133(+) hemSCs located pre-vascular in
proiferative IH tissues. Both beta1 and beta2-AR were expressed, while beta2-AR
was dominant on hemSCs. Propranolol at 100-150 MUM inhibited proliferation of
hemSCs, not did 50 MUM. Propranolol down-regulated VEGF expression of hemSCs,
instead of inducing apoptosis. The adipogenic potential was enhanced by
propranolol. Therefore, our current results suggested propranolol could not
induce apoptosis of hemSCs, but played a curative role though suppressing VEGF
synthesis and enhancement of adipogenesis of hemSCs. Our results might partially
provide the insight of mechanism of relapse in some cases on cessation of
propranolol treatment.
PMID- 25120758
TI - S100B ranks as a new marker of multiple traumas in patients and may accelerate
its development by regulating endothelial cell dysfunction.
AB - S100 calcium binding protein B (S100B) is recently known as the markers for
inflammatory diseases. However, its roles and underlying mechanism on multiple
traumas remain unclearly. In this study, total 123 patients (87 male and 36
female) were enrolled and divided into two group: Injury severity score (ISS) >=
16 (n = 69); ISS < 16 (n = 54). ELISA assay confirmed that the circulating S100B
levels in multi-trauma were obviously higher than that in healthy volunteers.
Additionally, S100B concentrations was associated with injury severity as an
obviously higher levels of S100B (2.18 MUg/L) in severe trauma group (ISS >= 16)
than 1.26 MUg/L in moderate trauma group (ISS < 16). Furthermore, the average
concentration of S100B was 2.91 MUg/L (n = 14) in fatal patients and 2.21 MUg/L
in survivors, suggesting an obvious correlation between S100B and the severity
degree of multi-injury. Further analysis confirmed an obvious correlation between
S100B levels and sE-selectin, and Von willebrand factor (vWF), both of these are
the marker of endothelial cell injury. After transfection with pcDNA3.1-S100B,
human umbilical vein endothelial cells (HUVECs) cell apoptotic ratio was
dramatically up-regulated, concomitant with the increase in IL-6 and IL-8 levels,
suggesting that S100B might regulate the development of polytrauma by mediating
endothelial cell dysfunction. Together, these results suggest a potential
predictive value of S100B and its underlying mechanism in the pathological
process of polytrauma. Therefore, this study will support the potential clinical
aspect for the diagnostic and treatment of polytrauma and its complications.
PMID- 25120759
TI - PNMA1 promotes cell growth in human pancreatic ductal adenocarcinoma.
AB - Paraneoplastic Ma1 (PNMA1) is a member of an expanding family of 'brain/testis'
proteins involved in an autoimmune disorder defined as paraneoplastic
neurological syndrome (PNS). Although it is widely studied in PNS, little is
known about the underlying clinical significance and biological function of PNMA1
in tumors. Here, we find that elevated PNMA1 expression is more commonly observed
in pancreatic ductal adenocarcinoma (PDAC) cell lines, compared with normal
pancreatic cell and tissues from pancreatic ductal adenocarcinoma patient.
Besides, higher PNMA1 expression is closely correlated with large tumor size.
Suppression of endogenous PNMA1 expression decreases cell viability and promotes
cell apoptosis. Subsequent studies reveal that the PI3K/AKT, MAPK/ERK pathway and
members of the anti-apoptotic Bcl-2 family may be involved in the pro-survival
and anti-apoptotic effect of PNMA1 on PDAC. Taken together, this study provides
evidence that PNMA1 is involved in tumor growth of pancreatic carcinoma and PNMA1
related pathways might represent a new treatment strategy.
PMID- 25120761
TI - RNAi-mediated silencing of the Skp-2 gene causes inhibition of growth and
induction of apoptosis in human renal carcinoma cells.
AB - Renal cancer ranks one of the most frequent causes of cancer death in the world.
S-phase kinase-associated protein 2 (SKP 2) is overexpressed in human tumors and
has prognostic value in many cancers including renal cancer, indicating its
potential as a therapeutic target. In this study, we investigated the therapeutic
potential of Skp-2 in renal cancer using the technique of RNA silencing via short
hairpin RNA (shRNA). Synthetic shRNA duplexes against Skp-2 were introduced to
down-regulate the expression of Skp-2 in a highly malignant renal carcinoma cell
line, ACHN. The results indicated that siRNA targeting of Skp-2 could lead to an
efficient and specific inhibition of endogenous Skp-2 activity. Furthermore, we
found that depletion of Skp-2 caused a dramatic cell cycle arrest, followed by
massive apoptotic cell death, and eventually resulted in a significant decrease
in growth, viability and tumor formation in renal cancer cell lines studied.
PMID- 25120760
TI - HMGB1 enhances smooth muscle cell proliferation and migration in pulmonary artery
remodeling.
AB - HMGB1 is a necessary and critical mediator of acute lung injury and can act as a
chemoattractant and anti-apoptosis factor in injury or repair in diseases. In
this study we sought to determine whether HMGB1 is involved in the remodeling of
pulmonary artery and investigate the mechanism. A rat model of pulmonary artery
remodeling was successful induced with LPS infusion and the increasing of
pulmonary arteries media was obviously inhibited in rats treated with thrice
inject of HMGB1 neutralizing antibody. The percent of areas of tunica media to
total artery wall was (0.53 +/- 0.15), (0.81 +/- 0.10) and (0.59 +/- 0.11) in
control, LPS and antibody group respectively (p<0.05). Meanwhile, treatment with
HMGB1 neutralizing antibody not only decreased the level of HMGB1 mRNA and
protein significantly, but inhibited the expression of PCAN and Bcl-2 as well. On
the contrary, Bax, a gen which represented the apoptosis, revealed an absolutely
reversed trend to Bcl-2 in pulmonary arteries. Experiments in vitro showed that
HMGB1 could stimulate the proliferation of hPASMC in MTT test and increase the
number of migrated cells in a concentration-dependent manner in chemotaxis assay
using modified Boyden chambers. In conclusion, data from this study support the
concept that HMGB1 is involved in the remodeling of pulmonary artery by enhancing
proliferation and migration of smooth muscle cell. Inhibiting HMGB1 may be a new
target to deal with the remodeling of pulmonary artery.
PMID- 25120762
TI - Identification of collaboration patterns of dysfunctional pathways in breast
cancer.
AB - Breast cancer (BC) is the most common malignancy among women. We aimed to
illuminate the molecular dysfunctional mechanisms of BC progression. The mRNA
expression profile of BC GSE15852 was downloaded from Gene Expression Omnibus
database, including 43 normal samples and 43 cancer samples. Differentially
expressed genes (DEGs) in BC were screened using the t-test by Benjamin and
Hochberg method. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the
selected DEGs were enriched using Hypergeomeric distribution model. In addition,
functional similarity network among the enriched pathways was constructed to
further analyze the collaboration of these pathways. We found 848 down-regulated
DEGs were associated with 16 significant dysfunctional pathways, including PPAR
signaling fatty acid metabolism, and 1584 up-regulated DEGs were related to 6
significant dysfunctional pathways, like cell cycle, protein export, and antigen
processing and presentation in BC samples. Crosstalk network analysis of pathways
indicated that pyruvate metabolism, propanoate metabolism, and glycolysis
gluconeogenesis were the pathways with closest connections with other pathways in
BC. In addition, other antigen processing and presentation, including 19 DEGs;
PPAR signaling pathway, including 18 DEGs; and pyruvate metabolism pathway,
including 13 DEGs were further analyzed. Our results suggested that dysfunctional
of significant pathways can greatly affect the progression of BC. Several
significant disorder pathways were enriched in our comprehensive study. They may
provide guidelines to explore the dysfunctional mechanism of BC progression.
PMID- 25120763
TI - Unclassified renal cell carcinoma: a clinicopathological, comparative genomic
hybridization, and whole-genome exon sequencing study.
AB - Unclassified renal cell carcinoma (URCC) is a rare variant of RCC, accounting for
only 3-5% of all cases. Studies on the molecular genetics of URCC are limited,
and hence, we report on 2 cases of URCC analyzed using comparative genome
hybridization (CGH) and the genome-wide human exon GeneChip technique to identify
the genomic alterations of URCC. Both URCC patients (mean age, 72 years)
presented at an advanced stage and died within 30 months post-surgery.
Histologically, the URCCs were composed of undifferentiated, multinucleated,
giant cells with eosinophilic cytoplasm. Immunostaining revealed that both URCC
cases had strong p53 protein expression and partial expression of cluster of
differentiation-10 and cytokeratin. The CGH profiles showed chromosomal
imbalances in both URCC cases: gains were observed in chromosomes 1p11-12, 1q12
13, 2q20-23, 3q22-23, 8p12, and 16q11-15, whereas losses were detected on
chromosomes 1q22-23, 3p12-22, 5p30-ter, 6p, 11q, 16q18-22, 17p12-14, and 20p.
Compared with 18 normal renal tissues, 40 mutated genes were detected in the URCC
tissues, including 32 missense and 8 silent mutations. Functional enrichment
analysis revealed that the missense mutation genes were involved in 11 different
biological processes and pathways, including cell cycle regulation, lipid
localization and transport, neuropeptide signaling, organic ether metabolism, and
ATP-binding cassette transporter signaling. Our findings indicate that URCC may
be a highly aggressive cancer, and the genetic alterations identified herein may
provide clues regarding the tumorigenesis of URCC and serve as a basis for the
development of targeted therapies against URCC in the future.
PMID- 25120764
TI - Monocyte chemotactic protein-1 expression as a prognosic biomarker in patients
with solid tumor: a meta analysis.
AB - PURPOSE: A great deal of studies have been performed on the prognostic value of
monocyte chemotactic protein-1 (MCP-1) in solid tumors in recent years. However,
no consistent outcomes are reported. Therefore, the prognostic value of MCP-1
still remains controversial in patients with solid tumors. Here we aimed to
evaluate the prognostic value of MCP-1 expression for patients with solid tumors.
METHODS: Comprehensive literature was selected from PUBMED and EMBASE and
clinical studies which reported analysis of survival data about MCP-1 in solid
tumors were included. Stata 11.0 was used for performing a meta-analysis on
evaluating the relation between MCP-1 and clinical staging, overall survival (OS)
and disease free survival (DFS). RESULTS: Eleven studies with a total of 1324
patients with solid tumors were included into our meta-analysis. The result
showed that high concentration of MCP-1 was related to a worse OS (HR = 1.95, 95%
CI 1.32-2.88). The subgroup analysis on different location of tumors showed that
high concentration of MCP-1 meant bad prognosis in patients with digestive cancer
(HR = 2.66, 95% CI 1.44-4.91) and urogenital cancer (HR = 2.23, 95% CI 1.61
3.10), even head and neck cancer (HR = 1.99, 95% CI 0.95-4.18) other than
respiratory cancer (HR = 1.10, 95% CI 0.39-3.11). Another subgroup analysed on
different sites of cancer and indicated a poor prognosis on adenocarcinoma (HR =
2.10, 95% CI 1.63-2.69). CONCLUSIONS: Our findings suggest that MCP-1 can be
regarded as a poor prognostic maker for solid tumors and may represent important
new therapeutic targets.
PMID- 25120765
TI - Increased HIF-1alpha expression in tumor cells and lymphocytes of tumor
microenvironments predicts unfavorable survival in esophageal squamous cell
carcinoma patients.
AB - The expression of hypoxia-induced factor (HIF)-1alpha is up-regulated in tumor
microenvironments under hypoxia condition. However, the prognostic significance
of HIF-1alpha in esophageal squamous cell carcinoma (ESCC) is still elusive. We
measured the HIF-1alpha expression by immunochemistry in tumor specimens from 136
resected ESCC; in the current study, the HIF-1alpha expression in tumor cells was
significantly associated with tumor stage (P = 0.003) and lymph node metastasis
(P = 0.006); whereas the HIF-1alpha expression in tumor-infiltrating lymphocytes
(TILs) had no relationship with patients' clinicopathological parameters.
Patients with high HIF-1alpha expression in tumor cells or in TILs showed worse
survival related to those with low HIF-1alpha expression. Multivariate analysis
demonstrated that expression of HIF-1alpha in TILs was an independent factor for
DFS (P = 0.007) and OS (P = 0.013). Additionally, the expression of HIF-1alpha in
tumor cells was an independent factor for DFS (P = 0.037) and OS (P = 0.033) in
locoregional ESCC patients, whereas the expression of HIF-1alpha in TILs was an
independent factor for DFS (P = 0.048) and OS (P = 0.039) in metastatic ESCC
patients. Correlation analysis revealed that expressions of HIF-1alpha in tumor
cells and in TILs were positively correlated, and patients with combined high HIF
1alpha in both tumor cells and TILs had the worst survivals (P < 0.05). These
findings suggest that the HIF-1alpha expressions in different cell populations of
ESCC microenvironments have different clinical relevance and prognostic impact on
patients.
PMID- 25120766
TI - RNAi screening identifies HAT1 as a potential drug target in esophageal squamous
cell carcinoma.
AB - Esophageal carcinoma (EC) is one of the most fatal carcinomas of the
gastrointestinal tract. Aberrant activity of histone acetyltransferases
(HATs)/deacetylases (HDACs) play a critical role in carcinogenesis through the
regulation of the genes involved in cell differentiation, proliferation, and
apoptosis. However, cellular functions of HATs/HDACs in esophageal cancer and its
molecular mechanisms remain unclear. An RNAi screen was used in this study to
identify the histone acetyltransferases (HATs) and deacetylases (HDACs) that
could be critical for the survival of EC cells. We demonstrated that HAT1
(histone acetyltransferase 1) was an important determinant to regulate the
proliferation of human EC Eca-109 cells. Furthermore, we showed that the
knockdown of HAT1 induced a G2/M cell cycle arrest, which was associated with the
disruption of cell cycle-related events, including the decrease of cyclinD1 as
well as alteration in cyclinB1 expression. The expression of HAT1 was validated
to be higher in the primary tumors and adjacent tissue as compared to that of the
normal esophageal tissue. Furthermore, we found that HAT1 expression was directly
correlated with the poor tumor differentiation of EC tissue, which suggested that
HAT1 played an important role in esophageal carcinoma and that it could be a
novel EC therapeutic target.
PMID- 25120767
TI - Nuclear localizaiton of beta-catenin is associated with poor survival and chemo
/radioresistance in human cervical squamous cell cancer.
AB - Nuclear expression of beta-catenin has been suggested as an independent
prognostic marker in a variety of cancers. The objective of this study was to
investigate the clinicopathologic significance of nuclear beta-catenin expression
in patients with cervical squamous cell carcinoma (CSCC). In this original
research article, we detected nuclear beta-catenin expression in 29/171 CSCC
tissues (17.0%). Patients without nuclear beta-catenin expression had a
significantly better outcome than patients with nuclear beta-catenin expression
(93.7% versus 82.7% P = 0.027). Furthermore, nuclear beta-catenin expression was
predictive of prognosis in CSCC patients with early stage disease (FIGO stage I
or tumor size <= 4 cm), with well/moderately differentiated tumors, or lymph node
metastasis. Interestingly, nuclear beta-catenin expression correlated with poor
outcome in patients who received postoperative chemotherapy or radiotherapy.
Multivariate analysis suggested that nuclear beta-catenin expression is an
independent prognostic indicator in CSCC. Our findings suggest that nuclear beta
catenin expression may be used as a prognostic biomarker in CSCC, especially for
patients with early stage disease, well/moderately differentiated tumors, or
lymph node metastasis. Moreover, nuclear beta-catenin expression has potential as
a predictive marker of chemoresistance and radioresistance in CSCC.
PMID- 25120768
TI - Overexpression of MAGE-D4 in colorectal cancer is a potentially prognostic
biomarker and immunotherapy target.
AB - Melanoma-associated antigen D4 (MAGE-D4) is a novel member of MAGE family. This
study aimed to examine the expression and immunogenicity of MAGE-D4 in colorectal
cancer (CRC) to determine its potential as a prognosis and immunotherapeutic
target. The expression of MAGE-D4 mRNA and protein was determined by RT-PCR and
immunohistochemistry (IHC) in CRCs with paired adjacent non-tumor tissues,
colorectal adenomas and normal colorectal tissues, respectively. Sera from 64 CRC
patients were tested for MAGE-D4 antibody by ELISA. MAGE-D4 mRNA was more
frequently expressed in CRCs (76.7%, 46/60) than in adjacent non-tumor tissues
(15.0%, 9/60). MAGE-D4 protein was detected in all the CRC tissues tested, 70.0%
of which showed high expression. There was no MAGE-D4 protein detected in any
paired adjacent non-tumor tissue. No MAGE-D4 expression was found in colorectal
adenomas and normal colorectal tissues by either RT-PCR or immunohistochemistry.
Patients with high MAGE-D4 protein expression had significantly shorter overall
survival than those with low MAGE-D4 protein expression (median, 68.6 vs 122.2
months; P=0.030). Furthermore, multivariate analysis exhibited high MAGE-D4
protein expression had a trend toward an independent prognostic factor (hazard
ratio: 6.124; P=0.050). Humoral immunity to MAGE-D4 was detected in 12 of 64
(18.8%) CRC patients' sera but not in 77 healthy donors. There was no correlation
between MAGE-D4 expression, serum antibody and clinicopathological parameters.
These findings suggest MAGE-D4 may serve as a potentially prognostic biomarker
and an attractive target of immunotherapy in CRC.
PMID- 25120769
TI - Expression of aquaporin 8 and phosphorylation of Erk1/2 in cervical epithelial
carcinogenesis: correlation with clinicopathological parameters.
AB - Overexpression of aquaporins (AQPs) has been reported in several human cancers.
Extracellular signal-regulated kinases 1/2 (Erk1/2) are associated with
tumorigenesis and cancer progression and may upregulate AQPs expression. In this
study, we examined cervical tissue samples to establish the relationship between
Erk1/2 and AQPs in cervical carcinoma by RT-PCR, Western blot and
immunohistochemistry. We also examined the relationship between AQP8, Erk1/2 and
clinicopathological variables in patients with cervical cancer. Our results
showed that Erk1/2 was differentially expressed at the level of transcription and
was most highly expressed in CIN samples (P < 0.05). At the level of translation,
significant differences were seen in the expression of AQP8, Erk1/2 and P-Erk1/2
(P < 0.05). Expression was highest in CIN samples, where 80.9%, 76.6%, and 66% of
samples were positive for AQP8, Erk1/2 and P-Erk1/2, respectively. Expression in
cervical carcinoma samples was higher than in normal cervical tissues (P < 0.01).
AQP8 expression was associated with the depth of invasion of cervical cancer
cells, and the expression of Erk1/2 and P-Erk1/2 was increased in earlier
clinical stages and in lymphatic metastasis. AQP8 expression was positively
correlated with Erk1/2 expression in cervical cancer. In conclusions, increased
AQP8, Erk1/2 and P-Erk1/2 expression may play a role in transformation of CIN
into cervical cancer, and in early invasion and lymphatic metastasis of cervical
cancer. These proteins could potentially be used as molecular markers for early
diagnosis of cervical carcinoma.
PMID- 25120771
TI - Inhibitory effect of beta-elemene on human breast cancer cells.
AB - It has been approved for the clinical application of beta-elemene to treat
various cancers mainly brain tumors in China. In the present study, we found that
beta-elemene significantly inhibited the in vitro growth of human breast cancer
cells by inducing apoptosis. In addition, beta-elemene also induced the
conversion of LC3-I into LC3-II as well as the formation of autolysosomes,
indicating the activation of autophagy. Interestingly, inhibition of autophagy
significantly potentiated the growth-inhibitory effect of beta-elemene on breast
cancer cells. In summary, beta-elemene induced cytoprotective autophagy in human
breast cancer cells in addition to apoptosis. Inhibition of autophagy
significantly enhanced the cytotoxicity of beta-elemene to human breast cancer
cells. Therefore, combination of beta-elemene with autophagy inhibitors could be
a promising strategy for the treatment of breast cancer.
PMID- 25120770
TI - Apigenin suppresses GLUT-1 and p-AKT expression to enhance the chemosensitivity
to cisplatin of laryngeal carcinoma Hep-2 cells: an in vitro study.
AB - Glucose transporter-1 (GLUT-1) and PI3K/Akt are known to be closely involved in
resistance to chemotherapy. Co-targeted therapy reducing GLUT-1 expression and
PI3K/Akt pathway activity may overcome the chemoresistance of human cancers.
Apigenin may inhibit the expression of GLUT-1 and the PI3K/Akt pathway. We
hypothesized that over-expression of GLUT-1 and p-Akt was associated with the
resistance to cisplatin of laryngeal carcinoma Hep-2 cells. We explored whether
apigenin inhibited GLUT-1 and p-Akt, resulting in sensitization of laryngeal
carcinoma Hep-2 cells to cisplatin. Real-time RT-PCR and Western blotting
confirmed the presence of GLUT-1 mRNA, and GLUT-1 and p-Akt proteins in Hep-2
cells. We found that resistance or insensitivity of Hep-2 cells to cisplatin
might be associated with such expression. Apigenin markedly enhanced the
cisplatin-induced suppression of Hep-2 cell growth. This effect was concentration
and time-dependent. Thus apigenin may significantly reduce the levels of GLUT-1
mRNA, and GLUT-1 and p-Akt proteins, in cisplatin-treated Hep-2 cells, in a
concentration- and time-dependent manner. To conclude, overexpression of GLUT-1
mRNA may be associated with the resistance to cisplatin of laryngeal carcinoma
Hep-2 cells. Apigenin may enhance the sensitivity to cisplatin of laryngeal
carcinoma cells via inhibition of GLUT-1 and p-Akt expression.
PMID- 25120772
TI - Effects of BMSCs interactions with adventitial fibroblasts in
transdifferentiation and ultrastructure processes.
AB - In this study an in vitro model of simulated blood vessel injury was used to
study the effects of bone marrow-derived mesenchymal stem cells (BMSCs)
morphology and to detect vascular smooth muscle actin (SM alpha-actin) expression
in the presence of adventitial fibroblasts. BMSCs from rats with DAPI-labeled
nuclei were co-cultured with adventitial fibroblasts for 7 days, while BMSCs
cultured alone served as controls. Cell morphology of BMSCs was assessed by laser
confocal microscopy and SM alpha-actin or calponin expression in BMSCs was
detected by immunofluorescence staining. The expression of SM alpha-actin mRNA
was identified using RT-PCR. Cell ultrastructure was assessed by electron
microscopy. The results demonstrate that BMSCs with DAPI-labeled nuclei were
smaller compared with fibroblasts, and their nuclei emitted a blue fluorescence.
Most BMSCs displayed a polygonal shape changing from their original long fusiform
shape. BMSCs with blue nuclei and red cytoplasm (SM alpha-actin positive or
calponin positive) were observed, and a substantial number of filaments were
present in the cytoplasm as observed under electron microscopy. The number of
these cells increased as a function of culture duration. However, SM alpha-actin
expression was weak and calponin expression was not detected in the control
group. This study provides important new information on the characterization of
artherosclerosis pathogenesis and vascular restenosis after blood vessel injury.
Our findings demonstrate that direct interactions with adventitial fibroblasts
can induce vascular smooth muscle-like cell differentiation in BMSCs.
PMID- 25120773
TI - Expression profiles of HA117 and its neighboring gene DPF3 in different colon
segments of Hirschsprung's disease.
AB - Hirschsprung's disease (HSCR) is characterized by the absence of enteric ganglion
cells along variable regions of the colon. Established theory demonstrates that
HSCR is the consequence caused by the abnormal arrest of the migration and
differentiation of neural crest-derived stem cells (NCSCs). And retinoid
signaling was considered to be involved. We speculated that, HA117, a retinoid
related transcript of a long noncoding RNA (LncRNA), may be involved in the
genesis of HSCR. In current research, colon specimens were collected from 25 HSCR
patients and grouped into 3 segments: proximal anastomosis, dilated segment and
stenotic segment. Real-Time PCR was used to analyze the expression profiles of
HA117 and its neighboring gene DPF3 in different colon segments. Fluorescence in
situ hybridization (FISH) was employed to detect the distribution of HA117 in the
gut wall. Immunohistochemistry was performed to analyze the protein expression of
DPF3 in different colon segments. HA117 expression in stenotic segment was higher
compared to proximal anastomosis and dilated segment (p < 0.05). Whereas DPF3b
mRNA was lower in stenotic segment than that in two other segments (p < 0.05).
FISH detected HA117 was distributed in mucosa and muscle layer, mainly present in
stenotic segment. Immunohistochemical staining showed that intensive DPF3
staining occurred in proximal anastomosis and the positive staining was hardly
observed in stenotic segment. The results suggested that HA117 may be a factor
exerting an anti-differentiation or or anti-maturation role in the genesis of
HSCR. This gave us a novel cue for better understanding the etiology of HSCR.
PMID- 25120774
TI - Possible prognostic significance of p53, cyclin D1 and Ki-67 in the second
primary malignancy of patients with double primary malignancies.
AB - Patients with two types of primary cancers are rare. In this study, we
investigated the expression of p53, cyclin D1, and Ki-67 in the second primary
malignancy. Tissue samples were obtained from the second primary cancer site of
43 patients who met the diagnostic criteria for double primary cancer. p53,
cyclin D1 and Ki-67 were determined using immunohistochemistry. Categorical
variables were compared using the Chi-squared test; correlation between data
scores and histology was calculated using the Spearman's rank-order correlation.
The expression rates of p53, cyclin D1 and Ki-67 in the second primary malignancy
site were 60.5%, 30.2% and 65.1% respectively. p53 expression showed
statistically significant association with tumor occurrence interval,
pathological grading and nodal metastasis (p < 0.05). Positive correlation was
detected between the expression of cyclin D1 and Ki-67 and the expression of p53
(r = 0.313, p = 0.041; r = 0.319, p = 0.037, respectively). High-expressing p53
or cyclin D second primary malignancies were associated with decreased overall
survival (p = 0.040 and p = 0.043, respectively). Ki-67 expression levels did not
exhibit statistically significant differences in survival. In conclusion,
elevated protein expression of p53, cyclin D1 and Ki-67 in the second primary
malignancy is an indicator of more aggressive malignant behavior of the secondary
tumor. These markers may have prognostic value in the clinical setting.
PMID- 25120775
TI - Knockdown of Aurora-B inhibits osteosarcoma cell invasion and migration via
modulating PI3K/Akt/NF-kappaB signaling pathway.
AB - Increasing evidences reveal that Aurora-B may be involved in metastasis of
malignant tumor. In this study, we investigated the inhibitory effect of Aurora-B
on invasion and migration of OS cells and the activity of PI3K/Akt/NF-kappaB
signaling pathway in vitro. The expression of Aurora-B and p-Akt (Ser473)
proteins was detected by immunohistochemistry in OS tissues from 24 patients with
pulmonary metastatic disease, and the relationship between Aurora-B and p-Akt was
investigated. The results showed that there was a positive correlation between
Aurora-B and p-Akt protein expression. Furthermore, we down-regulated the
expression of Aurora-B through a recombinant lentivirus (Lv-shAURKB). Migration
and invasion of cells were investigated by wound healing and transwell invasion
assays. Results showed that silencing Aurora-B inhibited cell migratory and
invasive ability of OS cells in vitro. Finally, knockdown of Aurora-B suppresses
the activity of PI3K/Akt/NF-kappaB signaling pathway in OS cells. Our results
indicated that knockdown of Aurora-B suppresses OS cells migratory and invasive
ability via modulating the "PI3K/Akt/NF-kappaB" signaling pathway in vitro. The
Aurora-B blocker may be a new therapeutic strategy in OS management.
PMID- 25120776
TI - Increased chromogranin A and neuron-specific enolase in rats with chronic
nonbacterial prostatitis induced by 17-beta estradiol combined with castration.
AB - Although chronic nonbacterial prostatitis (CNBP) is a common diagnosis in middle
aged men, the etiology of this disease remains poorly understood. Neuroendocrine
cells play an important role in the neuroendocrine regulation of the prostate,
and chromogranin A (CgA) and neuron-specific enolase (NSE) are regarded as
classic markers of neuroendocrine cells. This study aimed to determine CgA and
NSE levels in a CNBP rat model to evaluate the role of neuroendocrine cells in
the pathogenesis of CNBP. For developing a CNBP rat model, we examined the
ability of 17-beta estradiol and surgical castration alone or in combination to
induce CNBP. Histologic inflammation of the prostate was assessed in CNBP-induced
rats by hematoxylin-eosin staining, whereas CgA and NSE protein levels were
assessed by immunohistochemistry, Western blot analysis, and enzyme-linked
immunosorbent assays. Our results showed that 17-beta estradiol combined with
castration successfully induced CNBP and that CgA and NSE levels were increased
in the prostate of CNBP rats as compared to those without CNBP. These findings
indicate that the neuroendocrine regulation mediated by neuroendocrine cells may
be involved in the pathogenesis of CNBP.
PMID- 25120777
TI - Granular cell tumor of the esophagus: a clinicopathological study of 31 cases.
AB - Granular cell tumors (GCTs) in esophagus are rare tumors lacking of systemic
large group reports. In this study, we summarized the clinical characteristics,
histological features and therapeutic approaches of 31 cases. GCTs generally
located at middle and distal of the esophagus in middle aged and elderly patients
with no incidence of gender differences. Histologically, tumor cells were mainly
plump and polygonal with abundant, granular, amphophilic or eosinophilic
cytoplasm. The growth pattern was solid or nested, usually with minimal
infiltration and inflammatory infiltrates and lymphoid aggregation. All GCTs in
the present study were benign according to Nasser criteria. Nestin, NSE, CD68 and
S100 protein were moderate to strong positive. Moreover, a developmental
morphology of a GCT was found, which included areas of relatively normal Schwann
cells, transitional cells and typical cells of GCTs. All patients received
endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD).
Twenty-six patients were followed up and remained clinically well. In conclusion,
GCTs of esophagus are neurogenic origin tumors with favourable prognosis.
Definite diagnosis of GCTs relies upon pathological examination. The Nasser
criteria for stratification are practical in guiding treatment strategy. ESD is a
recommended therapeutic strategy, and the range of application is expanding.
PMID- 25120778
TI - Alterations of microRNAs are associated with impaired growth of MCF-7 breast
cancer cells induced by inhibition of casein kinase 2.
AB - BACKGROUND AND AIM: Protein Kinase (casein kinase 2, CK2) is a pleiotropic serine
threonine kinase that is frequently dysregulated in many human tumors; microRNAs
(miRNAs) are a class of small noncoding RNAs which play important roles in human
cancers. This study aimed to investigate the role of CK2 and miRNA expression in
breast cancer. METHODS: Casein kinase 2 in MCF-7 breast cancer cell line was
inhibited by the CK2 inhibitor TBB (4,5,6,7-tetrabromobenzotriazole), then cell
proliferation was studied using MTT assay, and cell cycle distribution and
apoptosis were detected by flow cytometry. The alteration of microRNAs expression
profile was determined by microarray technology, followed by RT-PCR confirmation.
RESULTS: Here, we for the first time showed that inhibition of CK2 in MCF-7
breast cancer cells causes suppressed cell growth, which was related with
dysregulation of the miRNA profile and altered expression. CK2 inhibition induced
the up-regulated expression of 17 miRNAs and 10 down-regulated microRNAs which
contributed to the impaired growth, inhibited cell cycle progress and increased
apoptosis of MCF-7 cells by a CK2 inhibitor. CONCLUSIONS: These findings
highlight the potential role of dysregulated miRNA expression regulated by CK2 in
breast cancer.
PMID- 25120779
TI - Cyclin D1b overexpression inhibits cell proliferation and induces cell apoptosis
in cervical cancer cells in vitro and in vivo.
AB - Cyclin D1b is one of two proteins translated from cyclin D1 transcripts (isoforms
a and b) that are generated due to gene polymorphism. Our previous study has
reported low cyclin D1b expression in cervical cancer tissue, with an expression
level in moderately or poorly differentiated tissues that was significantly lower
than that in well-differentiated tissues. However, the functional role of cyclin
D1b in cervical cancer remains to be elucidated. In this study, using a cervical
cancer cell line with stable expression of cyclin D1b, we found that upregulation
of cyclin D1b initiated cell cycle arrest at the G0/G1 phase and induced
apoptosis, thereby inhibiting cell proliferation and colony formation.
Furthermore, xenograft transplantation experiments in nude mice demonstrated that
cyclin D1b upregulation inhibited cancer growth and induce apoptosis in vivo. In
conclusion, the present study indicates anti-tumor effects of cyclin D1b in
cervical cancer, suggesting that cyclin D1b may represent a potential therapeutic
target for cervical cancer.
PMID- 25120780
TI - Different levels of circulating Th22 cell and its related molecules in Graves'
disease and Hashimoto's thyroiditis.
AB - PURPOSE: The aim of this study was to make a comparative analysis of the possible
different expression of Th22 cells in two subtypes of autoimmune thyroid diseases
(AITDs), i.e., Graves' disease (GD) and Hashimoto's thyroiditis (HT). METHODS: We
recruited 61 AITDs patients (31 GD and 30 HT) and 22 controls. Serum level of IL
22 was measured by enzyme linked immunosorbent assay (ELISA). The proportion of
Th22 cells in peripheral blood mononuclear cells (PBMCs) was analyzed by flow
cytometry. The messenger RNA (mRNA) expressions of IL-22, its receptors (IL10R2,
IL22R1) and key transcription factor (aryl hydrocarbon receptor, AHR) in PBMCs
were assayed by quantitative reverse transcription polymerase chain reaction (qRT
PCR). Several cytokines of the cultured PBMCs were also measured under IL-22
stimulation. RESULTS: The proportion of Th22 cells, serum IL22 level and IL-22
mRNA expression were significantly higher in patients with GD than in healthy
controls. Additionally, AHR increased in GD patients compared to healthy
controls. However, the elevation of Th22 cells and their relative cytokines was
not found in patients with HT. Consistent with specific mRNAs expression of
cultured PBMCs, IL-4 increment in supernatant was much higher in GD group than in
control group, while IFN-gamma levels were decreased under IL-22 stimulation.
CONCLUSION: Th22 cells may participate in the pathogenesis of AITDs as a
proinflammatory factor, especially in GD, through expressing and secreting IL-22.
PMID- 25120781
TI - Vascular alterations in schwannoma.
AB - Schwannomas or neurilemmoma are benign peripheral nerve sheath tumors, which most
frequently occur at the cerebellopontine angle. This morphologic study examines
vascular alterations in these tumors, comparing them to other benign spindle cell
neoplasms of the nervous system, while correlating these findings with evidence
of vascular permeability. Thirty-four nervous system spindle cell neoplasms,
sixteen schwannomas, nine fibroblastic/transitional meningiomas and nine
peripheral neurofibromas were stained with H&E, Prussian-blue stain, and
immunoreacted for factor VIII-related antigen and interstitial albumin.
Schwannomas had focal clusters of vascular proliferation including groups of
small thin-walled vessels, as well as larger vessels with extensive
hyalinization. Neurofibromas and meningiomas almost uniformly had modest numbers
of well-defined, thin walled individual vessels. Free hemosiderin and hemosiderin
laden macrophages were frequently identified in schwannomas. Prussian-blue stain
for iron revealed focal or fairly widespread positivity in almost all
schwannomas, only one meningioma and none of the neurofibromas. Immunoreaction
for albumin demonstrated leakage of vascular proteins into the interstitium
confirming tumor vessel permeability in schwannomas. Neither neurofibromas nor
meningiomas displayed any detectable interstitial albumin. The above findings
confirm a degree of reactive proliferation of vessels in schwannoma along with
functional deficits in their vascular integrity with permeability to protein and
blood. The presence of hyalinized vessels, hemosiderin, both free and within
macrophages, and more readily evident Prussian blue staining, may provide an
additional diagnostic clue in discriminating between histologically similar
spindle cell lesions. The study however raises the possibility that these changes
likely precede or facilitate the degenerative 'ancient change' seen in some
schwannoma.
PMID- 25120782
TI - miR-218 modulate hepatocellular carcinoma cell proliferation through
PTEN/AKT/PI3K pathway and HoxA10.
AB - PURPOSE: To investigate the regulatory mechanism of miR-218 in human
hepatocellular carcinoma (HCC). METHODS: qPCR was used to compare the expression
levels miR-218 among six hepatocellular carcinoma cell lines and normal liver
tissues. After transfecting MHCC97L cells with either miR-218 mimics or miR-218
inhibitor, western blotting was used to examine the expressing patterns of
cyclinD1, p21, and PTEN/AKT/PI3K signaling pathway-related proteins. MTT and
colony forming assay was used to assess the capability of cell proliferation.
Bioinformatic method was applied to predict the binding of miR-218 on HoxA10, and
western blotting was used to examine the modulatory effect of miR-218 AND HoxA10
on PTEN/AKT/PI3K pathway in HCC. RESULTS: The expression levels of miR-218 were
frequently lower in HCC cell lines than in normal liver tissues. Over-expression
of miR-218 in HCC cells significantly decreased cell proliferation whereas
inhibiting miR-218 promoted cancer cell proliferation. Western blotting analysis
demonstrated that tumorigenesis related protein cyclin D1 and p21, as well as
PTEN/AKT/PI3K signaling pathways were actively modulated by miR-218 in HCC cells.
The expression of endogenous HoxA10 was also down-regulated by miR-218 over
expression, and silencing HoxA10 directly activated PTEN in HCC cells.
CONCLUSION: Modulation of miR-218 actively affected HCC cancer cell development.
The regulatory mechanism of miR-218 in HCC cells was acting through PTEN/AKT/PI3K
pathway and possibly associated with HoxA10.
PMID- 25120783
TI - Neutrophil-to-lymphocyte ratio (NLR) predicts mortality and adverse-outcomes
after ST-segment elevation myocardial infarction in Chinese people.
AB - Neutrophil-to-lymphocyte ratio (NLR) has been reported to predict cardiovascular
risks and mortality in coronary artery diseases. We aimed to evaluate the
capacity of NLR to predict long-term mortality in Chinese patients presenting
with ST-segment elevation myocardial infarction (STEMI). We recorded NLR at
admission, 24 or 72 hours after admission, and at discharge (14+/-2 days) of 692
patients presenting with STEMI at Xuanwu hospital, Beijing between 2002 and 2005,
and assessed the capacity of NLR to predict mortality during follow up (median
9.43, interquartile range (IQR) 8.65-10.28 years). Backward stepwise multivariate
Cox regression revealed that average inpatient NLR (NLRaverage) predicted all
cause mortality (Hazard ratio 1.481) more accurately than absolute leukocyte and
neutrophil counts (P<0.001). When patients were stratified into tertiles by
NLRaverage (T1 NLR<3.16, T3 NLR>4.75), patients in T3 exhibited a 4.621-fold
higher risk of mortality than patients in T1 (P=0.002). Patients in T3 had a
significantly higher incidence of all-cause mortality (10.00%) than T1 (2.17%)
and T2 (4.31%), cardiac-mortality (8.70%) than T1 (2.17%) and T2 (4.31%),
hypotension (20.00%) than T1 (5.65%) and T2 (12.93%), arrhythmia (43.91%) than T1
(24.14%) and T2 (24.35%), and defibrillation (7.83%) than T1 (1.74%) and T2
(5.17%) in hospital; and suffered from higher mortality (46.09%) than T1 (9.13%)
and T2 (29.74%), cardiac mortality (27.83%) than T1 (5.22%) and T2 (15.52%) and
MACE events (36.52%) than T1 (13.04%) and T2 (31.9%) during long-term follow-up.
Average NLR was a useful and powerful predictor of mortality and adverse-outcomes
in Chinese patients presenting with STEMI.
PMID- 25120784
TI - Clinicopathological features of hepatitis B virus recurrence after liver
transplantation: eleven-year experience.
AB - OBJECTIVE: We sought to investigate new changes in the clinical pathology of
hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT)
in era of new nucleoside or nucleotide analogues. METHODS: One hundred and eighty
four adult patients who underwent OLT for HBV-related end-stage liver disease
between 1999 and 2010 were enrolled in this study. Of these patients, 156
received lamivudine (LAM) plus hepatitis B immune globulin (HBIG) and 28 were
treated with LAM. The liver function, serologic parameters and HBV-DNA of the 184
recipients were followed up, and clinical pathological characteristics of grafts
with HBV recurrence were examined in this study. RESULTS: One hundred and seventy
nine (97%) were alive at their last follow-up and eleven (6%) had developed HBV
recurrence at a median of 22 (range 6 to 46) months post-OLT. Two of the 11
recipients were detected with HBV-S gene mutation, and 5 were tested with YMDD
mutation. Four recipients who died of irreversible graft dysfunction secondary to
HBV recurrence, developed fibrosing cholestatic hepatitis (FCH) because of no
effective antiviral agents available in the early stages of HBV recurrence after
OLT. Six recipients who received adefovir (ADV) (and Entecavir, ETV) in the early
stages of HBV recurrence after OLT achieved improvement in hepatic histology.
CONCLUSIONS: HBV recurrence post-OLT could be controlled at an acceptable level
for a long time and the recipients could achieve long-term survival by using new
antiviral agents, instead of advancing into FCH in the short term after HBV
recurrence.
PMID- 25120785
TI - Dynamic metabolites profile of cerebral ischemia/reperfusion revealed by (1)H NMR
based metabolomics contributes to potential biomarkers.
AB - Current metabolomic studies of ischemic brain mainly attach importance on a
certain ischemic period, are lack of data about dynamic metabolites in ischemic
stroke process, especially early period. Thus, in this study, (1)H NMR
spectroscopy was used to investigate biochemical changes in the early stages of
rats' focal cerebral ischemia reperfusion (I/R) injury. Serum samples of 0, 0.5,
1, 3, 6, 12, 24 h of reperfusion, based on multivariate data analyses, were
tested to analyze the changing of metabolites during the early disease process.
Partial least squares-discriminant analysis scores plots of the (1)H NMR data
revealed clear differences among the experiment groups. Combination the results
of loading plot and t-test, we found that 13 metabolites were changed
significantly. Among that, malonic acid and glycine are the most noticeable
variable metabolites. Dramatic changed malonic acid and glycine most probably
served as biomarkers in this study. These findings help us understand the
biochemical metabolite changes in early ischemic stroke stages, especially
different periods. That may be conducive to distinguish at-risk individuals,
benefit early diagnosis and understand the dynamic pathogenesis of early cerebral
ischemia.
PMID- 25120786
TI - Immunohistochemical study for the origin of ductular reaction in chronic liver
disease.
AB - The appearance of proliferating bile ductular structures, which is called the
"atypical ductular reaction" is frequently observed in various chronic liver
diseases associated. However, the origin of these increased bile ductules has
been a matter of controversy. In this study, we investigated the origin of
ductular cells as an aspect of relation between epithelial to mesenchymal
transition (EMT) and epithelial members of liver parenchyme, such as hepatocyte
and cholangiocyte by immunohistochemical staining of human liver. Thirteen
specimens of surgically resected liver with biliary cirrhosis were selected.
Three sets of double immunohistochemical stains were done; Hep-Par 1 -
cytokeratin 19 (CK19), Hep-Par 1 - alpha-sm ooth mus cle actin (alpha-SMA) and
CK19 - alpha-SMA. As a result, we investigated the dual expression of the markers
of hepatocyte and cholangiocyte in the same cell; in ductular cell and
surrounding hepatocyte. However, there seems to be no dual expression of markers
for EMT with epithelial markers. This study suggests a possibility of phenotypic
change of mature hepatocyte into cholangiocyte. Future studies will be necessary
to determine the role that proliferating cholangiocytes play in the pathogenesis
of biliary fibrosis and how cholangiocytes interact with other cell types of the
liver such as hepatic stellate cells or Kupffer cells.
PMID- 25120787
TI - Prognostic value of hormone receptor status conversion following neoadjuvant
chemotherapy in a series of operable breast cancer patients.
AB - BACKGROUND: To investigate the prognostic value of hormone receptor (HR) status
conversion after neoadjuvant chemotherapy (NAC) in patients with primary breast
cancer. METHODS: 267 stage II-III breast cancer patients treated with NAC who had
residual disease in the breast after NAC were retrospectively studied. The
patients were divided into four groups based on the HR status: Group A, patients
with HR-positive both before and after NAC; Group B, patients with HR status
positive-to-negative change; Group C, patients with HR status negative-to
positive change; Group D, patients with HR-negative both before and after NAC.
Patients with positive HR status (regardless of before or after NAC) were treated
with adjuvant endocrine therapy, and a survival analysis was performed. RESULTS:
In total, 15.7% of patients had HR status change after NAC. progression-free
survival (PFS) in Group A was similar to that in Group C (hazard ratio, 1.16; P =
0.652), but that in Group B was significantly lesser than that in Group A (hazard
ratio, 6.88; P = 0.001), and that in Group C was significantly longer than that
in Group D (hazard ratio, 6.88; P = 0.001). A similar pattern of results was
obtained for overall survival (OS). CONCLUSIONS: The switch of HR status after
NAC is remarkable for breast cancer. An HR switch may identify patients who would
benefit from adjuvant endocrine therapy and impact the long-term outcome.
PMID- 25120789
TI - Decreased LINE-1 methylation levels in aldosterone-producing adenoma.
AB - PURPOSE: Abnormal global DNA methylation levels are associated with many
diseases. In this study, we examined long interspersed nuclear elements-1 (LINE
1) methylation as a biomarker for abnormal global DNA methylation and aldosterone
producing adenoma (APA). METHODS: Tissues from 25 APA and 6 normal adrenal glands
(NAs) were analyzed for LINE-1 methylation by real-time methylation-specific
polymerase chain reaction. The estimated LINE-1 methylation level was then tested
for correlation with the clinicopathologic parameters of APA patients. RESULTS:
The methylation index (MI) level for LINE-1 was 0.91 in NA samples and 0.77 in
APA samples (P < 0.001). For the APA samples, there were no statistical
correlations between the MI level and various clinicopathologic parameters such
as gender (P = 0.07). CONCLUSION: LINE-1 methylation is significantly lower in
APA samples than in NA samples. LINE-1 methylation is not correlated with the
clinical characteristics of APA.
PMID- 25120790
TI - Expression and clinical significance of cancer-testis genes in clear cell renal
cell carcinoma.
AB - Cancer-testis (CT) antigens, which are encoded by CT genes, have been recognized
as a group of highly attractive targets for cancer immunotherapy. However, the
expression and clinical relevance of CT genes in clear cell renal cell carcinoma
(ccRCC) remains largely unknown. The present study aims to analyze the expression
profile of 6 individual CT genes including MAGE-A1, MAGE-A3, MAGE-A12, cTAGE-1,
cTAGE-2, and NY-ESO-1 in ccRCC and further investigate their possible
correlations with clinicopathologic characteristics. The mRNA expressions of
these CT genes were detected using reverse transcriptase-polymerase chain
reaction (RT-PCR) in 105 ccRCC tissue samples (T1-2 in 70 samples, T3-4 in 35
samples; G1-2 in 65 samples, G3-4 in 40 samples) as well as the paired adjacent
normal tissues. The most frequently expressed CT gene was MAGE-A3 (27.6%),
followed by MAGE-A12 (23.8%), NY-ESO-1 (21%), MAGE-A1 (20%), cTAGE-1 (17.1%), and
cTAGE-2 (14.3%). In contrast, no expression of CT genes was detected in the
paired adjacent normal tissues. Furthermore, the MAGE-A3 protein expression was
determined by Western blot and immunohistochemistry. MAGE-A3 protein was
expressed in 21.9% ccRCC samples with a cytoplasmic staining pattern. No MAGE-A3
protein expression was found in the paired adjacent normal tissues. There was a
significant correlation between MAGE-A3 expression at both mRNA (P =0.045) and
protein (P = 0.03) levels with advanced stages of the disease. Taken together, CT
genes may serve as promising targets of specific immunotherapy for ccRCC and
particularly, MAGE-A3 may serve as a potential prognostic marker for ccRCC
patients.
PMID- 25120788
TI - Transcription factors related to epithelial mesenchymal transition in tumor
center and margin in invasive lung adenocarcinoma.
AB - The tumor microenvironment has many roles involving tumor progression, invasion
and metastasis. The tumor cells at the tumor border loose epithelial properties
and acquire mesenchymal features. This, epithelial-to-mesenchymal transition
(EMT) has been suggested to be an important process for tissue and lymphovascular
invasion. Pulmonary tissue samples from 15 patients with primary adenocarcinoma
were evaluated with using immunofluorescence multi-staining the EMT-associated
markers including E-cadherin and alpha-smooth muscle actin (alpha-SMA), and
transcription factors including E-SNAIL and SLUG, and ZEB1. The data were
analyzed in specific area, such as tumor center and tumor border. In this study
we show that the invasive adenocarcinoma differentially expressed SNAIL and SLUG,
and Zeb1 and it was associated with the loss of epithelial marker (E-cadherin)
and gaining of mesenchymal marker (alpha-SMA) at the invasive border of lung
carcinoma. The positive rates of SNAIL and ZEB1 were 26.7% and 0% in the tumor
center and 40% and 20% in tumor margin, respectively. In addition, the expression
of both SNAIL and ZEB1 at the border of tumor was observed in two cases (2/10).
These two cases were associated with lymph node metastasis and advanced stage.
The process of EMT has been suggested to be of prime importance for tissue and
lymphovascular invasion. The process of EMT may be activated in the tumor border
of lung adenocarcinoma. Related transcription factors, such as SNAIL and SLUG,
and ZEB1, might be induced by paracrine effects of surrounded inflammatory cells
and fibroblasts.
PMID- 25120791
TI - Decreased RGS6 expression is associated with poor prognosis in pancreatic cancer
patients.
AB - Regulator of G-protein signaling 6 (RGS6), a member of a family of RGS proteins,
has been reported to involve in multiple processes during tumor development.
However, its role in pancreatic cancer has not been studied yet. In this study,
we aimed to investigate the expression of RGS6 in pancreatic cancer and its role
in predicting outcomes of patients with pancreatic cancer. We first measured the
expression of RGS6 mRNA in 20 cases of tumor tissues and matched adjacent non
tumorous tissues by quantitative real-time PCR and examined RGS6 protein by
immunohistochemistry in tissue microarrays containing 90 tumor and 90 paired
adjacent non-tumor tissues. Decreased RGS6 mRNA detected in primary tumor,
compared with their non-tumor counterparts. In addition, decreased RGS6 protein
expression was associated with tumor differentiation (P = 0.027), pT
classification (P = 0.034), smoking status (P = 0.041) and a poor survival (P =
0.007). Cox proportional hazards regression modeling analysis revealed that lymph
node metastasis (P = 0.001; hazard ratio, 2.347, 95% CI, 1.387-3.972), tumor
differentiation (P = 0.015; hazard ratio, 0.505, 95% CI, 0.291-0.876) and RGS6
expression (P = 0.048; hazard ratio, 0.567, 95% CI, 0.324-0.994) were three
independent prognostic factors. Taken together, these date demonstrate that RGS6
decreases in tumor tissue and may serve as a novel biomarker for outcomes in
pancreatic cancer patients and be a potential therapeutic target potential
therapeutic target.
PMID- 25120794
TI - Complement membrane attack complex is related with immune-mediated necrotizing
myopathy.
AB - This study is to investigate the expression of complement membrane attack complex
(C5b-9) in the skeletal muscle of patients with necrotizing myopathy (NM), and to
investigate the relationship between C5b-9 and NM. Thirteen patients with NM and
control patients with polymyositis and muscular dystrophy were enrolled in this
study. Examinations including creatine kinase (CK) and L-lactate dehydrogenase
(LDH) in the serum, electromyogram and muscle pathological examination were
performed. C5b-9 expression in the skeletal muscle was determined by
immunohistochemistry and analyzed by Image Plus Pro 6.0. C5b-9 expression was
particularly prominent in necrotic muscle fibers, and also positive in blood
vessels. C5b-9 diffusely expressed in vascular endothelial cells and smooth
muscle layer. But the intensity was not related with the elevated level of serum
CK. So, C5b-9 is strongly expressed in the necrotic muscle fiber and blood
vessels, and may contribute to the pathogenesis of NM.
PMID- 25120792
TI - A new 5-grading score in the diagnosis of prostate cancer with real-time
elastography.
AB - OBJECTIVE: To evaluate the clinical significance of transrectal real-time
elastography (TRTE) in diagnosis of prostate cancer (PCA). METHODS: 195 patients
with an elevated PSA level were enrolled in the study. A novel 5-grading score of
prostate outer gland was applied by TRTE imaging. Receiver-operating
characteristic curve (ROC) analyses were performed to assess the diagnostic
performance of TRTE score. RESULTS: TRTE scores in patients with PCA and benign
condition were 3.20 +/- 1.11 (range: 1-5) and 2.24 +/- 1.01 (range: 1-4),
respectively (P < 0.001). The best cutoff value of TRTE score was 3, and the
sensitivity, specificity, accuracy in the diagnosis were 68.6% (35/51), 69.4%
(100/144) and 69.2% (135/195), respectively. The accuracy of TRTE in volume <= 30
ml group was significantly higher than that in the volume >= 50 ml group and the
30-50 ml group (76.9% vs. 65.0% and 76.9% vs. 71.4%, both P < 0.001). Accuracy of
TRTE score was higher for those with PSA ranged 4-10 ng/ml than those with PSA >
10 ng/ml (85.3% vs. 66.7%, P = 0.002). CONCLUSION: TRTE score, a novel semi
quantitative assessment of patients' prostate stiffness, can be served as a
useful screening method for patients suspicious of PCA, especially those only
having an elevated PSA level.
PMID- 25120795
TI - Metastasis-associated colon cancer-1 is a novel prognostic marker for cervical
cancer.
AB - AIMS: To investigate metastasis associated in colon cancer 1 (MACC1) expression
in cervical cancer. METHODS: One hundred and four paraffin-embedded cervical
cancer specimens were immunohistochemically analyzed for MACC1 expression. The
expression of MACC1 in 8 pairs of cervical cancer and adjacent normal cervical
tissues were detected by Real-time PCR. RESULTS: MACC1 expression was upregulated
in cervical cancer tissues compared with adjacent normal cervical tissues.
Patients with higher MACC1 expression had shorter overall survival time, whereas
those with lower ASAP1 expression survived longer (P = 0.029). Moreover, high
expression of MACC1 was correlated with FIGO stage (P = 0.039) and lymph nodes
metastasis (P = 0.003) of this disease. Multivariate analysis revealed that MACC1
was an independent prognostic factor (P = 0.043) for the overall survival of
cervical cancer patients. CONCLUSION: Our study suggests that MACC1 may
contribute to tumor development and progression in cervical cancer, and that
MACC1 could be a useful marker for the prognosis of cervical cancer.
PMID- 25120793
TI - Ileal interposition reduces blood glucose levels and decreases insulin resistance
in a type 2 diabetes mellitus animal model by up-regulating glucagon-like peptide
1 and its receptor.
AB - This study is to explore the possible mechanism of ileal interposition (IT)
treatment of glycemic control of the type 2 diabetes mellitus (T2DM) by
establishing an IT animal model. Twelve T2DM rats (GK rats) of 8-week old were
divided into GK IT surgery group (GK-IT) and GK sham group (GK-Sham). Six Wistar
rats were used as the non-T2DM sham group (WS-Sham). Enzyme-linked immunosorbent
assay was used to detect plasma insulin concentration and fasting pancreas
glucagon-like peptide-1 (GLP-1) concentration changes. Homeostasis model
assessment of insulin resistance was used to quantitatively measure insulin
resistance. Glucagon-like peptide-1 receptor (GLP-1R) expression was detected by
Western blotting. IT significantly decreased fasting blood glucose level and the
oral glucose tolerance, and reduced insulin resistance of GK rats by increasing
GLP-1 concentration and GLP-1R levels. The postoperative pancreatic beta-cell
apoptosis rate of GK-Sham group was significantly higher than those in the GK-IT
group and the WS-Sham group. IT significantly reduces blood glucose and decreases
insulin resistance by up-regulating GLP-1 concentrations and GLP-1R levels, which
may contribute to insulin secretion of pancreatic beta-cells and decreases
apoptosis of pancreatic beta-cell.
PMID- 25120796
TI - Sex-specific association of the peptidase D gene rs731839 polymorphism and serum
lipid levels in the Mulao and Han populations.
AB - Little is known about the association of peptidase D (PEPD) gene rs731839 single
nucleotide polymorphism (SNP) and serum lipid profiles in the Chinese population.
The objective of the present study was to detect the association of the PEPD
rs731839 SNP and serum lipid levels in the Mulao and Han populations. Genotyping
of the PEPD rs731839 SNP was performed in 751 subjects of Mulao and 762 subjects
of Han using polymerase chain reaction and restriction fragment length
polymorphism and then confirmed by direct sequencing. The A allele carriers had
higher serum high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo)
AI levels and lower triglyceride (TG) levels in Mulao; and higher HDL-C, low
density lipoprotein cholesterol (LDL-C) and ApoAI levels in Han than the A allele
non-carriers. Subgroup analyses showed that the A allele carriers had higher HDL
C, ApoAI levels and lower TG levels in Mulao males but not in females; higher
total cholesterol (TC), HDL-C, LDL-C and ApoAI levels in Han males; and higher
TG, HDL-C and ApoAI levels in Han females than the A allele non-carriers. Serum
lipid parameters were also correlated with several environmental factors in Mulao
and Han populations, or in males and females in both ethnic groups. The
association of the PEPD rs731839 SNP and serum lipid levels was different between
the Mulao and Han populations, and between males and females in the both ethnic
groups. There may be an ethnic- and/or sex-specific association of the PEPD
rs731839 SNP and serum lipid levels in our study populations.
PMID- 25120799
TI - Serum levels of microRNA-133b and microRNA-206 expression predict prognosis in
patients with osteosarcoma.
AB - The aim of the present study was to investigate whether the aberrant expression
of microRNA (miR)-133b and miR-206 can be used as potential prognostic markers of
human osteosarcoma. Quantitative real-time reverse transcriptase-polymerase chain
reaction (qRT-PCR) analysis was performed to detect the expression levels of miR
133b and miR-206 in 100 pairs of osteosarcoma tissues and matched noncancerous
bone tissues, and serum samples from 100 patients with osteosarcoma as well as in
serum samples from 100 healthy controls. As a result, expression levels of miR
133b and miR-206 were both significantly decreased in osteosarcoma tissues and
patients' sera (both P<0.001). Then, the downregulation of miR-133b and miR-206
both more frequently occurred in osteosarcoma patients with high tumor grade
(both P=0.01), positive metastasis (both P<0.001) and recurrence (both P<0.001).
Moreover, the patients with low miR-133b expression and low miR-206 expression
both had shorter overall survival (OS, both P<0.001) and disease-free survival
(DFS, both P<0.001) than those with high expressions. Of note, the OS and DFS of
patients with combined low expression of miR-133b and miR-206 (miR-133b-low/miR
206-low) were the shortest (both P<0.001). Furthermore, low miR-133b expression,
low miR-206 expression and conjoined expression of miR-133b/miR-206 were all
independent prognostic factors for OS and DFS of osteosarcoma patients.
Collectively, the aberrant expression of miR-133b and miR-206 may be implicated
in tumorigenesis and tumor progression of osteosarcoma. More interestingly,
detection of serum miR-133b and miR-206 expression could be further developed as
novel, non-invasive and efficient markers for prognosis in patients with
osteosarcomas.
PMID- 25120797
TI - Expression of ALDH1 and TGFbeta2 in benign and malignant breast tumors and their
prognostic implications.
AB - The specific mechanism underlying the role of putative stem cell marker aldehyde
dehydrogenase 1 (ALDH1) playing in development and progression of breast cancer
is currently unclear. Transforming growth factor beta (TGFbeta) signaling pathway
is reported to be activated in most cancers. Thus a study was initiated to
explore possible differences and correlation of ALDH1 and TGFbeta2 expression in
the most common malignant and benign tumors of the breast in Chinese women.
Samples of 75 breast cancer tissues, 30 paracancerous normal tissues, and 39
fibroadenoma breast tissues were investigated for the expression of ALDH1 and
TGFbeta2 using immunohistochemistry. The positive rates of ALDH1 and TGFbeta2
protein were 62.67% and 66.67%, respectively, in breast cancer tissues, which
were significantly higher than that in normal fibroadenoma breast (P<0.05) and
paracancerous tissues (P<0.01). ALDH1 and TGFbeta2 status were significantly
associated with tumor histological grade and receptor status (P<0.05). Expression
of ALDH1 was found to be positively correlative to TGFbeta2 in breast cancer (r =
0.33, P<0.01). Expression of both proteins remained significantly associated with
reduced overall survival (OS) by univariate analysis (P<0.05). Multivariate Cox
regression analysis showed that ALDH1 expression, tumor stage, and lymph node
status are independent prognostic factors in invasive breast cancer patients.
Thus ALDH1 and TGFbeta2 play important roles in the development of breast cancer.
The ALDH1 phenotype is an independent predictor of poor prognosis, and TGFbeta2
signaling pathway activation might be involved in the pathological regulation of
ALDH1 in breast cancer.
PMID- 25120800
TI - Expression of O(6)-methylguanine DNA methyltransferase (MGMT) and its clinical
significance in gastroenteropancreatic neuroendocrine neoplasm.
AB - O(6)-methylguanine-DNA methyltransferase (MGMT) is a widespread DNA repair enzyme
defending against mutation caused by guanine O(6)-alkylating agents. Until now,
we know only little about the expression of MGMT in gastroenteropancreatic
neuroendocrine neoplasm (GEP-NEN). To study the expression of MGMT and its
clinical significance in GEP-NEN, 174 specimens of GEP-NEN were examined, of
which 152 specimens came from The First Affiliated Hospital, Sun Yat-sen
University during October 1995 to November 2013, 22 specimens came from Peking
Union Medical College Hospital during September 2004 to April 2010. MGMT protein
was detected with EnVision immunohistochemical staining method.
Clinicopathological factors were also collected and analyzed. We observed that
the overall expression rate of MGMT was 83.9%. Over expression of MGMT protein
was not associated with sex, age, functional status, primary tumor location,
grading, classification, TNM stage and metastasis (P > 0.05). Kaplan-Meier
analysis revealed that there was no significant difference in survival between
MGMT-positive and MGMT-negative tumors of GEP-NEN patients (chi(2) = 0.887, P =
0.346). In multivariate analyses carried out by Cox proportional hazards
regression model, MGMT expression was also not an independent predictors of
survival. These results demonstrated that MGMT protein was highly expressed in
GEP-NEN. MGMT deficiency rate was similar in pancreatic NEN and in
gastrointestinal NEN. MGMT expression was not correlated with prognosis of GEP
NEN.
PMID- 25120798
TI - The absence of human papillomavirus in esophageal squamous cell carcinoma in East
China.
AB - Esophageal squamous cell carcinoma (ESCC) is one of the most common types of
tumors worldwide, particularly in China, and human papillomavirus (HPV) is
thought to be a potential risk factor for this cancer. To determine whether this
is true, we collected 177 formalin-fixed and paraffin-embedded ESCC samples from
two hospitals. We screened for 23 different HPV genotypes using a human
papillomavirus genotyping kit, which allowed us to amplify the L1 gene by
polymerase chain reaction (PCR) and test for 23 HPV subtypes by reverse dot blot
(RDB) on a single membrane. We also used immunohistochemistry (IHC) to detect the
P16(INK4a) protein, the expression of which is linked to HPV E7 activity and
which is used to diagnose cervical intraepithelial neoplasia. The genotyping
results showed that only six samples were weakly positive for HPV: two for HPV16,
two for HPV11 and two for HPV35, with no samples showing strong positive signals.
The IHC results showed only five samples with diffuse positive staining, with the
other samples being completely negative or having only focal positive signals,
which were considered as negative. This study demonstrates that the HPV infection
rate in ESCC samples is very low, suggesting that HPV is not the etiological
cause of ESCC.
PMID- 25120802
TI - HER2-positive mucinous adenocarcinomas of the ovary have an expansile invasive
pattern associated with a favorable prognosis.
AB - Ovarian primary mucinous adenocarcinomas (MACs) are refractory to conventional
therapy. Biomarkers for ovarian MAC could facilitate prognosis and targeted
therapy, but are not currently available. The expression of human epidermal
growth factor 2 (HER-2) has been linked to enhanced survival of MAC patients and
may hold potential as a biomarker, but this potential has not been sufficiently
investigated. In this study, we examined the clinicopathological features of 46
cases of MAC and 36 cases of patients with mucinous borderline tumors (MBTs). The
expression of estrogen receptors (ER), progesterone receptors (PR), and HER2 were
measured by immunohistochemistry and fluorescent in situ hybridization (FISH).
Next, we compared the clinicopathological characteristics according to the HER2
expression profile. MBTs of the endocervical type tended to have simultaneous ER
and PR expression (P = 0.0028) while MACs rarely showed ER or PR expression. HER2
expression was observed in 14 out of the 46 MACs (37.84%) and in none of the MBTs
(P = 0.0002). HER2-positive MACs occurred approximately 10 years earlier than
HER2-negative MACs (35.21 +/- 4.768 years compared to 46.78 +/- 1.977 years; P =
0.0105). All HER2-positive MACs demonstrated an expansile invasive pattern, while
all MACs with infiltrative invasion pattern were HER2-negative (P = 0.0406).
Kaplan-Meier survival analysis demonstrated a tendency for improved overall
survival in HER2-positive MACs compared to HER2-negative MACs (P = 0.0389). In
conclusion, HER2 overexpression in ovarian MACs is associated with an expansile,
but not an infiltrative, invasion pattern and a favorable prognosis. Therefore,
we suggest that HER2 may be a practical marker for histopathological
categorization and a prognostic marker in ovarian MACs.
PMID- 25120801
TI - High level of microtubule-associated protein light chain 3 predicts poor
prognosis in resectable esophageal squamous cell carcinoma.
AB - Microtubule-associated protein light chain 3 (LC3) is a key mediator bridging
autophagy, apoptosis and differentiation. However, its role and clinical
significance in resectable esophageal squamous cell carcinoma (ESCC) is still
scanty. The purpose of this study was to investigate the clinical significance of
LC3 by immunohistochemistry in a group of patients with ESCC treated with
surgical resection. Tissue microarray that included 253 surgically resected ESCC
specimens was successfully generated for immunohistochemical evaluation. The
clinical/prognostic significance of LC3 expression was analyzed statistically.
The association of LC3 expression with the ESCC survival rate was assessed by
Kaplan-Meier and Cox proportional-hazards regression. The results showed that the
immunostaining of LC3 was distributed in cytoplasm and plasma-membrane.
Significantly high LC3 expression was found in ESCC cells compared with that of
normal esophageal epithelial cells. Patients with low expression of LC3
demonstrated higher overall survival compared with those with high expression of
LC3 (mean of 71.1 months versus 55.5 months, P = 0.022). A similar result was
observed for disease-free survival (mean of 68.7 months versus 51.8 months, P =
0.021). In subgroup analysis, LC3 expression could stratify pN0 patients with
ESCC. Multivariate analysis showed that the level of LC3 expression was an
independent prognostic factor in ESCC (RR = 1.407, P = 0.049). This paper shows
high level of LC3 suggests poor prognosis for resectable ESCC patients.
PMID- 25120803
TI - Bromodomain 4 protein is a predictor of survival for urothelial carcinoma of
bladder.
AB - BACKGROUND: Bromodomain 4 (BRD4) protein is a double bromodomain-containing
protein that binds preferentially to acetylated chromatins. BRD4 is essential for
cellular growth and has been implicated in cell cycle control, DNA replication
and carcinogenesis. However, its expression profile and prognostic value in
urothelial carcinoma of the bladder (UCB) have not been investigated. METHODS:
Real-time quantitative PCR (qRT-PCR) and Western blot were used to explore BRD4
expression in UCBs and normal bladder tissues. Moreover immunohistochemistry
(ICH) was used to detect the expression of BRD4 in UCBs. Spearman's rank
correlation, Kaplan-Meier plots and Cox proportional hazards regression model
were used to analyze the data. RESULTS: Up-regulated expression of BRD4 mRNA and
protein was observed in the majority of UCBs by qRT-PCR and Western blot when
compared with their paired normal bladder tissues. Clinicopathological analysis
was showed a significant correlation existed between the higher expression of
BRD4 protein with the histological grade, lymph node metastasis and distant
metastasis (P < 0.05); Survival analysis by Kaplan-Meier survival curve and log
rank test demonstrated that elevated BRD4 expression in bladder cancer tissue
predicted poorer overall survival (OS) compared with group in lower expression.
Notably, multivariate analyses by Cox's proportional hazard model revealed that
expression of BRD4 was an independent prognostic factor in UCB. CONCLUSIONS:
These results suggest that the aberrant expression of BRD4 in human UCB is
possibly involved in the tumorigenesis and development, and the BRD4 protein
could act as a potential biomarker for prognosis assessment of bladder cancer.
Further studies on the cellular functions of BRD4 need to address these issues.
PMID- 25120804
TI - Bortezomib-based chemotherapy regimens can improve response in newly diagnosed
multiple myeloma patients with bcl-2 and survivin overexpression.
AB - OBJECTIVE: To investigate the relationship between the Bcl-2 and survivin
expression and the different regimens therapeutic efficacy newly diagnosed
multiple myeloma (NDMM). METHODS: We retrospectively assessed the association of
Bcl-2 and survivin expression with chemotherapeutic efficacy and prognosis in 59
NDMM patients in a single center. RESULTS: The positive expression rate for
survivin and Bcl-2 was 35% and 74%, respectively. Survivin and Bcl-2 protein
expression were not associated with clinical stage, suggesting that they are not
related to tumor burden in NDMM. Bortezomib-based regimens were more effective in
reducing tumor burden and achieving therapeutic (complete and partial) response
compared with non-bortezomib-based regimens irrespective of Bcl-2 or survivin
expression (P < 0.05). In cases with both negative Bcl-2 and survivin expression
(Bcl-2(-)survivin(-)), the response to bortezomib and non-bortezomib-based
regimens was similar (p = 0.429). Bcl-2 and survivin expression were not
correlated with overall survival (OS); however, Bcl-2-survivin- cases showed a
trend towards a longer OS (P = 0.078). CONCLUSION: We recommend bortezomib
containing regimens for NDMM with single or double-positive Bcl-2 and survivin
expression.
PMID- 25120805
TI - DeltaNp63, CK5/6, TTF-1 and napsin A, a reliable panel to subtype non-small cell
lung cancer in biopsy specimens.
AB - Histopathological subtyping of nonsmall cell lung cancer (NSCLC) is currently
important in selecting specific therapeutic agents. It can be challenging in
distinguishing poorly differentiated lung adenocarcinoma (AC) from squamous cell
carcinoma (SCC) on small biopsy samples. This study was aimed to evaluate the
utility of a panel of immunohistochemical markers consisting of DeltaNp63 (p40),
cytokeratins (CK) 5/6, thyroid transcription factor-1 (TTF-1) and napsin A (novel
aspartic proteinase of the pepsin family) in subtyping poorly differentiated
NSCLC. Forty-eight cases of NSCLC that could not be further classified by
examination of hematoxylin-eosin (H&E)-stained slides on biopsy and had
subsequent resection specimens were selected. Subtyping of the tumor was based on
the resection specimen using the World Health Organization criteria. DeltaNp63
was expressed in all 16 SCCs (100%), and was negative in all ACs and LCCs. CK5/6
was positive in 13 of 16 SCCs (81%), and was negative in all ACs and LCCs. TTF-1
was positive in 20 of 25 ACs (80%) and 3 of 7 LCCs (43%), but none of 16 SCCs.
Napsin A was positive in 16 of 25 ACs (64%) and was negative in all SCCs and
LCCs. Our study shows that a panel including DeltaNp63, CK5/6, TTF-1, and napsin
A allows correct subclassification of 39 of 48 cases of NSCLC on biopsy and may
contribute to refine lung cancer classification in biopsy specimens, remarkably
reducing the NSCLC-NOS (not otherwise specified) diagnostic category.
PMID- 25120806
TI - Decreased expression of receptor tyrosine kinase of EphB1 protein in renal cell
carcinomas.
AB - Receptors tyrosine kinase of Eph superfamily plays an important role in human
cancers. We previously found that EphB1 subtype is down-regulated in gastric
cancer, colorectal cancer and ovary serous carcinoma. Fore the more, the
decreased expression of EphB1 is related to invasion and metastasis in cancers.
Although EphB1 has been revealed as an important receptor in cancers, our
understanding of its roles in renal cell carcinoma (RCC) is limited. In the
present study, using specific anit-EphB1 polyclonal antibody and
immunohistochemistry, we evaluated EphB1 protein expression levels in RCC
specimens surgically resected from 82 patients (including 62 conventional clear
cell RCC, 10 papillary, and 10 chromophobic RCC cases). We found EphB1 protein is
positively expressed in the epithelium of renal tubules. Decreased expression of
EphB1 was found in all RCC carcinomas compared with expression in the normal
epithelium of renal tubules. EphB1 protein moderately expressed in chromophobic
RCC, weakly expressed in clear-cell RCC and negatively expressed in papillary
RCC. Our results indicate that EphB1 may be involved in carcinogenesis of RCC,
the molecular mechanisms of down-regulation of EphB1 including genetic and
epigenetic alterations and the dedicated roles of EphB1 in occurrence and
progress of RCC need to be explicated in next step.
PMID- 25120807
TI - Association between mir-24 and mir-378 in formalin-fixed paraffin-embedded
tissues of breast cancer.
AB - BACKGROUND: MiR-24/378 is thought to be onco-miRNAs for their ability of
enhancing tumor growth. The objective of this study was to evaluate the potential
predictive value of miR-24/378 expression in formalin-fixed paraffin-embedded
tissues of breast cancer patients. METHODS: The expression of miR-24/378 was
examined in 101 breast cancer patients and 40 controls using real-time
quantitative PCR. All statistical analyses were performed using SPSS16.0.
RESULTS: We found that miR-24 and miR-378 were significantly up-regulated in
breast cancer patients compared with controls (all P < 0.01). The expression
levels of the two miRNAs were highly correlated with each other in breast cancer
patients, with r = 0.778 between miR-24 and miR-378. Moreover, the two miRNAs
exhibited great capability of discriminating between cancer patients and controls
by ROC analysis. MiR-24 and miR-378 showed 0.79 and 0.807 AUC values
respectively. CONCLUSIONS: Over-expression of miR-24 and miR-378 in FFPE tissue
of breast cancer patients might conduct as an ideal source for biomarker
discovery and validation in breast cancer patients.
PMID- 25120808
TI - Synchronous primary triple carcinoma of thyroid and kidney accompanied by
solitary fibrous tumor of the kidney: a unique case report.
AB - Thyroid cancers coexisted with kidney cancer in a patient is an unusual event.
Here, we described a case of 35-year-old woman with synchronous occurrence of
primary papillary carcinoma and follicular carcinoma of the thyroid, accompanied
by renal cell carcinoma and solitary fibrous tumor of the kidney, which has not
been reported in literature to our best knowledge. Its clinical and pathological
features, as well as the possible pathogenic factors were discussed.
PMID- 25120809
TI - S-1 monotherapy as second line chemotherapy in advanced gastric cancer patients
previously treated with cisplatin/infusional fluorouracil.
AB - The treatment choice of advanced gastric carcinoma after failure from first-line
therapy is quite limited. To evaluate the efficacy and toxicity of S-1
monotherapy in patients with advanced gastric cancer after failure of first line
cisplatin and fluorouracil combination (CF). S-1 monotherapy as a second line
treatment was given to the patients who had failed to CF combination in SC-101
study. The efficacy and toxicity of S-1 monotherapy were evaluated exploratory.
The results indicated that forty-one patients received S-1 as a second line
therapy after disease progression. The overall response rate and disease control
rate were 14.6% and 41.5%, respectively. The median progression free survival
(PFS) was 5.1 months (ange: 2.9~6.2 month). The median overall survival time was
6.4 months. The survival rates at 6 month and 1 year were 56% and 7.3%,
respectively. Grade 3/4 adverse events were uncommonly occurred, including anemia
(2.4%), neutropenia (2.4%), thrombocytopenia (4.9%) and rash (2.4%). There were
no unexpected or life-threatening toxicities. Only one patient experienced dose
reduction due to grade 3 rash. In conclusion, S-1 monotherapy provided a mild
response rate and overall survival, and a favorable toxicity profile in the
second line setting after the first line failure to cisplatin and fluorouracil
combination.
PMID- 25120810
TI - C-kit and PDGFRA gene mutations in triple negative breast cancer.
AB - In this study, we evaluated C-kit immunohistochemical expression and C-kit and
platelet derived growth factor receptor A (PDGFRA) gene mutations in triple
negative breast cancer. 171 cases were analyzed by immunohistochemical staining
for the expression of C-kit and 45 cases, including 10 C-kit negative cases and
35 C-kit positive cases, were performed for C-kit gene mutations in exons 9, 11,
13 and 17 and PDGFRA gene mutations in exons 12 and 18. C-kit expression was
detected in 42.1% of triple negative breast cancers. Only 1 activating mutation
was detected in exon 11 of C-kit gene in 1 case. No activating mutations were
found in the other 44 cases. C-kit expression is a frequent finding in triple
negative breast cancers; 1 activating mutation which was also found in
gastrointestinal stromal tumors was detected; a few cases might benefit from
imatinib.
PMID- 25120811
TI - Notch1 single nucleotide polymorphism rs3124591 is associated with the risk of
development of invasive ductal breast carcinoma in a Chinese population.
AB - Accumulated evidence has revealed the presence of Notch receptor polymorphisms in
non-tumorous diseases; however, few studies have investigated the association of
Notch polymorphisms with breast cancer risk. A total of 100 invasive ductal
carcinoma (IDC) and 50 ductal carcinoma in situ (DCIS) patients and 100 usual
ductal hyperplasia (UDH) controls were genotyped for the following Notch receptor
single nucleotide polymorphisms (SNPs) using matrix-assisted laser
desorption/ionization time-of-flight mass spectrometry: Notch1, rs3124591;
Notch2, rs11249433; Notch3, rs3815188, and rs1043994; and Notch4, rs367398, and
rs520692. Immunohistochemistry was used to determine the effect of Notch
polymorphisms on corresponding Notch protein expression in successfully genotyped
patients. The frequency of rs3124591 TC genotype was significantly higher in IDC
(24.7%, 20/81) and DCIS (30%, 12/40) patients than in UDH controls (8%, 8/97) (P
= 0.002 and P = 0.011, respectively). However, the distribution of other SNP
genotypes was not significantly different between IDC and DCIS patients and UDH
controls. The frequency of TC genotype was significantly higher in poorly
differentiated tumors than in well-differentiated and moderately differentiated
tumors (P = 0.022). Importantly, a positive correlation between the rs3124591 TC
genotype and high Notch1 protein expression was observed in DCIS patients (P =
0.043) but not in IDC patients. This is the first study to suggest an increased
risk of IDC and DCIS of the breast for the Notch1 rs3124591 variant. Furthermore,
given the inconsistent associations between the rs3124591 variant and Notch1
expression in IDC and DCIS, this variant may affect breast cancer risk through
mechanisms in the latter stage other than alterations in Notch1 protein
expression.
PMID- 25120812
TI - Over-expression of p53, p21 and Cdc2 in histologically negative surgical margins
is correlated with local recurrence of laryngeal squamous cell carcinoma.
AB - The aim of this study was to explore the relationship between the expression of
p53, p21 and Cdc2 in the early laryngeal cancer with negative pathological
margins and its local recurrence. During 2004-2010, a total of 85 patients with
early laryngeal cancer were selected in Tangshan Union Hospital, Hebei, China,
and immunohistochemical method was used to detect the expression of p53, p21 and
Cdc2 in the negative pathological margin tissues. All patients were followed up
for two years to collect pathological data for evaluating the survival and tumor
recurrence. Two years after surgery 14 of 85 patients with laryngeal cancer
presented with recurrence (recurrent group), while 71 patients without recurrence
(none recurrent group). The positive rate of p53, p21 and Cdc2 protein in
laryngeal cancer tissues was 60.0% (51/85), 38.8% (33/85) and 70.6% (60/85),
respectively, while that of the three proteins in the cancer adjacent tissues was
36.5% (31/85), 21.2% (18/85) and 29.4% (25/85), respectively. The differentiation
and TNM stage of tumor had no correlation with the three proteins. The positive
rate of p53 in the surgical margin of the recurrent group and non recurrent group
was 71.4% (10/14) and 29.6% (21/71) (P = 0.003), that of p21 was 50.0% (7/14) and
15.5% (11/71), (P = 0.011) and Cdc2 was 57.1% (8/14) and 23.9% (17/71) (P =
0.030), respectively. In conclusion, p53, p21 and Cdc2 may be involved in the
occurrence, development and recurrence of laryngeal squamous cell carcinoma.
Overexpression of p53, p21 and Cdc2 in the surgical margin of early laryngeal
cancer is closely related to local recurrence of tumor.
PMID- 25120813
TI - Down-regulation of long non-coding RNA GAS5 is associated with the prognosis of
hepatocellular carcinoma.
AB - INTRODUCTION: Long non-coding RNAs (lncRNAs) have been investigated as a new
class of regulators of cellular processes, such as cell growth, apoptosis, and
carcinogenesis. lncRNA GAS5 has recently been identified to be involved in
tumorigenesis of several cancers such as breast cancer, lung cancer and renal
cancer. However, the regulation of GAS5 in hepatocellular carcinoma (HCC) has not
yet been reported before. METHODS: Expression of GAS5 in tumor and their normal
matched tissues was determined by quantitative real-time PCR in n = 71 HCC
patients, and its association with overall survival of patients was analyzed by
statistical analysis. RESULTS: The expression level of GAS5 was reduced in HCC in
comparison to normal matched tissues (P < 0.05). It is also proved that GAS5
expression was to be associated with HCC tumor size, lymphnode metastasis and
clinical stage (P < 0.05). In addition, the Kaplan-Meier survival curves revealed
that low GAS5 expression was associated with poor prognosis in HCC patients. GAS5
expression was an independent prognostic marker of overall HCC patient survival
in a multivariate analysis. CONCLUSIONS: The study proved for the first time that
GAS5 down regulated in a majority of HCC patients. Our results indicated that
GAS5 expression was an independent prognostic factor for patients with liver
cancer, which might be a potential valuable biomarker for HCC.
PMID- 25120814
TI - A comparison of ARMS and mutation specific IHC for common activating EGFR
mutations analysis in small biopsy and cytology specimens of advanced non small
cell lung cancer.
AB - We have compared mutation analysis by Amplification Refractory Mutation System
(ARMS) and epidermal growth factor receptor (EGFR) mutant-specific antibodies for
their ability to detect two common activating EGFR mutations in a cohort of 115
advanced non-small cell lung cancer (NSCLC), including cytology material, core
biopsy, and bronchoscopic biopsies. Assessment of EGFR mutation status was
performed by using antibodies and ARMS assay specific to the two major forms of
mutant EGFR, exon 19 deletion E746-A750 (c.2235_2249del15 or c.2236_2250del15, p.
Glu746_Ala750 del) and exon 21 L858R point mutation (c.2573T>G, p.Leu858Arg). In
this study the optimal buffer for antigen retrieval was sodium citrate (pH 6.0).
Q score was used to evaluate the specific mutant EGFR proteins expression.
Validation using clinical material showed deletions in exon 19 were detected in
19.1% and L858R mutation in 20% of all cases by ARMS assay. A cutoff value of
score 1 was used as positive by IHC. No wild type cases were immuno-reactive. The
antibodies performed well in cytology, core biopsies and bronchoscopic biopsies.
There were only one false positive case using L858R IHC (sensitivity 100%,
specificity 98.5%, positive predictive value 96%, negative predictive value
100%). All 23 E746-A750 exon 19 deletions identified by mutation analysis were
positive by IHC. The sensitivity of exon 19 IHC for E746-A750 was 100%,
specificity 100%, positive predictive value 100% and negative predictive value
100%. The result of the IHC stains was finely correlated with mutations status
determined by ARMS assay. Although inferior to molecular genetic analysis of the
EGFR gene, IHC is highly specific and sensitive for the targeted EGFR mutations.
The antibodies are likely to be of clinical value in cases especially where
limited tumor material is available, or in situations where molecular genetic
analysis is not readily available.
PMID- 25120815
TI - Urinary 6-sulfatoxymelatonin level in diabetic retinopathy patients with type 2
diabetes.
AB - Melatonin is a powerful antioxidant. Decreased melatonin excretion has been
reported to be associated with several oxidative stress-related diseases. The
urinary metabolite of melatonin, 6-sulfatoxymelatonin (aMT6s), has proved to be a
very reliable index of melatonin production. The present study aims to evaluate
the level of urinary aMT6s in patients with type 2 diabetes mellitus and diabetic
retinopathy. Urine samples were collected from 10 patients with diabetes and no
diabetic retinopathy (NDR), 19 patients with nonproliferative diabetic
retinopathy (NPDR), 38 patients with proliferative diabetic retinopathy (PDR),
and 16 subjects without diabetes mellitus, who served as controls. The level of
aMT6s in specimens was assayed by a commercial aMT6s ELISA kit, creatinine levels
were also measured for each sample to get urinary aMT6s/creatinine ratio.
Creatinine-adjusted urinary aMT6s values were compared among four groups. The
urinary aMT6s (mean +/- SD) levels were 9.95 +/- 2.42, 9.90 +/- 2.28, 8.40 +/-
1.84 and 5.58 +/- 1.33 ng/mg creatinine in the controls and in patients with NDR,
NPDR, or PDR, respectively. The urinary aMT6s level of the PDR group was
significantly lower than that of the control, NDR and DR groups. No significant
difference was found among the control, NDR and DR groups. After adjustment for
various factors (age, smoking, cancer, and coronary heart disease) that may
influence the aMT6s level, the odds-ratio of urinary aMT6s comparing PDR patients
to controls was 0.246 (95% confidence interval = 0.108-0.558, P = 0.001).
Therefore, the urinary aMT6s level is significantly decreased in diabetic
patients with PDR but not in diabetic patients without PDR, which indicates that
decreased urinary aMT6s level may be associated with the pathogenesis of PDR.
PMID- 25120816
TI - Immunohistochemical analysis using a BRAF V600E mutation specific antibody is
highly sensitive and specific for the diagnosis of hairy cell leukemia.
AB - Hairy cell leukemia (HCL) is usually diagnosed by morphology and flow cytometry
studies. However, it is challenging sometimes to distinguish HCL from its mimics.
Recently, the BRAF V600E mutation has been described as a disease-defining
molecular marker for HCL which is present in nearly all cases of HCL but
virtually absent in mimics of HCL. In this study, we investigated the possibility
of using immunohistochemical detection of the BRAF V600E mutant protein to
differentiate HCL from its mimics. A total of twenty-eight FFPE tissue specimens
were studied, including HCL (n=12), HCL variant (HCL-v, n=3), splenic marginal
zone lymphoma (SMZL, n=6), and other marginal zone lymphomas (MZL, n=7).
Immunohistochemical studies were performed using a mouse monoclonal antibody
(clone VE1, Spring Bioscience, CA) specific for BRAF V600E mutation. Molecularly
confirmed BRAF V600E mutation positive and negative cases were used as the
positive and negative controls respectively. All 12 cases of HCL showed
cytoplasmic BRAF V600E protein expression in leukemia cells by
immunohistochemical study regardless of tumor burden, whereas all cases of HCL
mimics including HCL-v, SMZL, and MZL were negative for BRAF V600E protein. Using
this BRAF V600E mutation specific antibody, this immunohistochemical study has
100% sensitivity and 100% specificity for the diagnosis of HCL in our cohort. In
conclusion, immunohistochemical detection of the BRAF V600E mutant protein is
highly sensitive and specific for the diagnosis of HCL. Compared to PCR or
sequencing-based methodologies, immunohistochemistry is a relatively rapid and
inexpensive alternative for the differential diagnosis between HCL and its
mimics.
PMID- 25120817
TI - Characteristics of demyelinating Charcot-Marie-Tooth disease with concurrent
diabetes mellitus.
AB - PURPOSE: Charcot-Marie-Tooth disease (CMT) is the most common type of inherited
peripheral neuropathy and has a high degree of genetic heterogeneity. CMT with
concurrent diabetes mellitus (DM) is rare. The purpose of this study is to
explore the genetic, clinical and pathological characteristics of the patients
with CMT and concurrent DM. METHODS: We investigated gene mutations (the
peripheral myelin protein 22 gene, myelin protein zero gene, lipopolysaccharide
induced tumor necrosis factor-alpha factor gene, early growth response gene and
the neurofilament light chain gene loci) of a relatively large and typical
Chinese family with CMT1 and concurrent DM2. From the literature, we also
retrieved all reported families and single cases with CMT and concurrent DM. We
comprehensively analyzed the characteristics of total 33 patients with CMT and
concurrent DM, and further compared these characteristics with those of patients
of diabetic peripheral neuropathy (DPN). RESULTS: Patients with CMT and
concurrent DM had some relatively independent characteristics and pathogenic
mechanisms. So we designated that kind of characteristic demyelinating CMT which
accompanies DM as Yu-Xie syndrome (YXS), a new specific clinical subtype of CMT.
CONCLUSION: CMT is an etiologic factor of DM, even though the intrinsic
association between CMT and DM still remains further exploration.
PMID- 25120818
TI - Lack of association between rs3807989 in cav1 and atrial fibrillation.
AB - BACKGROUND: A novel gene Caveolin-1(CAV1) was identified to be susceptibility to
PR interval and also associated with atrial fibrillation (AF) in two Genome wide
associations studies (GWAS) studies in European ancestry. The purpose of this
study was to determine the association of the SNPs in CAV1 gene of rs3807989 with
AF in Chinese Han patients. METHODS AND RESULTS: We attempted a replication in a
cohort of 839 Chinese AF patients and 1215 healthy controls using melting
temperature shift allele-specific genotyping analysis. One SNP in CAV1
(rs3807989) was genotyped. The final study cohort consisted of 839 AF patients
and 1215 healthy controls. No significant association was detected between
rs3807989 and AF in a Chinese Han population (allelic P-adj = 0.828 with OR =
1.02; genotypic P-adj = 0.815, 0.405, 0.760 with a dominant model, recessive
model, and additive model). After logistic regression with multiple covariates,
the association remained non-significant with adjusted P value 0.828. When the AF
cases were further divided into lone AF (31.5%) and other types of AF (68.5%), no
significant association was found between rs3807989 and lone AF (P-adj = 0.929
with OR = 0.990) and other types of AF (P-adj = 0.597 with OR = 1.060).
CONCLUSION: The SNP rs3807989 in CAV1 gene is not associated with AF or lone AF
in our studies, which suggests that the SNP rs3807989 in CAV1 may not be a risk
factor for AF in Chinese Han population.
PMID- 25120819
TI - Associated liver enzymes with hyperlipidemic profile in type 2 diabetes patients.
AB - Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and is
associated with dyslipidemia and disturbed liver function. Aim of the present
work is to assess the liver enzymes and to find its association with
hyperlipidemic profile in T2DM. Total of 157 subjects were studied and divided
into two groups; diabetes (n=81) and non-diabetes (n=76). Various biochemical
parameters like fasting glucose, post prandial glucose, HbA1c, total cholesterol
(TC), triglycerides (Tg), high density lipoprotein cholesterol (HDL-C), alanine
amino transferase (ALT), aspartate amino transferase (AST) and gamma-glutamyl
transferase (GGT) were analyzed by ROCHE module Cobas 6000 (C501 & C601)
analyzer, kits were procured by ROCHE diagnostics. Low density lipoprotein
cholesterol (LDL-C) was estimated by Freidwald's formula. Statistical analysis
was performed by applying student t test and Pearson's correlation coefficient,
at 0.0001 and 0.05 level of significance, respectively. All the glycemic control
parameters, lipid profile parameters except HDL-C and liver enzymes were found
increased in diabetes group and significantly differ from non-diabetes group
(p>0.0001). ALT showed significant positive correlation with fasting glucose,
post prandial glucose, HbA1c, TC, Tg, LDL-C and GGT at p>0.05. AST showed very
weak relation with all parameters while GGT was positively associated with
fasting glucose, post prandial glucose, HbA1c, TC, Tg, LDL-C and ALT at p>0.05.
In conclusion, T2DM incline to elevate liver enzymes, especially ALT and GGT were
of significance. Routine screening of ALT and GGT in T2DM patients may assists
early detection of liver abnormalities and to arrest the progress of disease.
PMID- 25120820
TI - Clear cell changes in mucinous tubular and spindle cell carcinoma: cytoplasmic
pallor/clearing within tubules, vacuoles or hybrid conventional clear cell
carcinoma of kidney?
AB - Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare and recently
recognized subtype of renal cell carcinoma (RCC). Apart from the classic
morphology comprising conventional three components, there exist a large number
of non-classic morphological variants of MTSCC, which make it necessity to
differentiate from other RCC. Herein, we report two non-classic morphological
variants of MTSCC. Case 1, a 85 years old man, showed numerous vacuoles among
inherent components and cytoplasmic pallor/clearing within tubules mimicking
conventional clear cell RCC with a 8.5 years follow-up, while Case 2 indicated a
"mucin-poor" MTSCC associated with simultaneous conventional clear cell RCC at
her age of 73 years. Until now Case 1 carries the longest disease-free survival
reported in literature since MTSCC was defined and ranks the oldest since
reported in literature, while Case 2 is the first report of "mucin-poor" MTSCC
associated with simultaneous conventional clear cell RCC. Now, since no
biomarkers or imagining tools but pathological examination can confirm the
diagnosis of MTSCC, the management is always following the guideline of RCC in
clinical practice. Generally, most reports consider it as a good prognosis
disease, but sarcomatoid variant, even classic subtype can progress rapidly to
life-threatening disease.
PMID- 25120821
TI - Pathogenesis of fulminant monkeypox with bacterial sepsis after experimental
infection with West African monkeypox virus in a cynomolgus monkey.
AB - The pathogenesis of severe human monkeypox, which causes systemic and fulminant
infections, is not clear. This study presents a case repot of fulminant monkeypox
with bacterial sepsis after experimental infection with monkeypox virus in a
cynomolgus monkey (Macaca fascicularis). In our previous study (Saijo et al.,
2009, J Gen Virol), two cynomolgus monkeys became moribund after experimental
infection with monkeypox virus Liberia strain, West African strain. One exhibited
typical monkeypox-related papulovesicular lesions. The other monkey presented
fulminant clinical symptoms with a characteristic flat red rash similar to that
found in smallpox, which is associated with extremely high fatality rates. In
this study, we found that the monkey with flat red rash had high levels of
viremia and neutropenia, as well as high plasma levels of pro-inflammatory
cytokines and chemokines compared with the other monkey. Monkeypox virus
replicates in epithelial cells and macrophages in various organs. Sepsis due to
Gram-positive cocci was confirmed histopathologically in the monkey with flat red
rash. The lack of inflammatory response in the lesion suggested that the monkey
with sepsis experienced strong immune suppression during the viral infection. The
neutropenia and excessive inflammatory cytokine responses indicate that
neutrophils play key roles in the pathogenesis of systemic and fulminant human
monkeypox virus infections with sepsis.
PMID- 25120822
TI - Spontaneous regression of breast cancer with axillary lymph node metastasis: a
case report and review of literature.
AB - Spontaneous regression (SR) of cancer is a rare but well-documented biological
phenomenon. However, the mechanism remains to be elucidated. We herein report a
case of the SR of breast cancer at both the primary site and metastatic axillary
lymph node with spontaneously-induced T cell-mediated immunological responses. A
52-year-old female with a lump in the left axilla was diagnosed to have a small
breast carcinoma with a distinct axillary lymph node metastasis. During the
preoperative systemic examination, she was diagnosed to have severe type 2
diabetes mellitus, was treated with insulin, and the hyperglycemia was normalized
after one month. Surgery for left breast cancer was then performed. The
postoperative histopathological examination revealed the SR of breast cancer at
both the primary site and metastatic axillary lymph node. Immunohistochemical
studies revealed that estrogen receptor positive, AE1/AE3-positive ductal
carcinoma completely underwent necrosis associated with extensive infiltration of
CD3-positive T cells in the tumor nodule in the lymph node. In addition, primary
ductal carcinoma cells also underwent single cell necrosis with infiltration of T
cells with lymph follicle-like organization of B cells in the mammary gland. The
features were suggestive that the tumor eradication in the metastatic lymph node
and regression of the primary ductal carcinoma could be due to host T cell
response to the ductal carcinoma. As far as we know it is the first report that
shows the spontaneous regression of breast cancer, probably due to the
spontaneously-induced T cell response.
PMID- 25120823
TI - Primary platelet-derived growth factor-producing, spindle-shaped diffuse large B
cell lymphoma of the skull: a case report and literature review.
AB - A 39-year-old woman with a right frontal mass underwent a cranial bone tumor
biopsy. Histopathologic examination of hematoxylin and eosin-stained slides
showed spindle-shaped tumor cells in a storiform pattern, appearing somewhat like
a sarcoma. However, the tumor cells were CD20-positive by immunohistochemical
staining. Therefore, a diagnosis of spindle-shaped diffuse large B-cell lymphoma
(Sp-DLBCL) was made. There have been at least 35 cases of Sp-DLBCL documented in
the literature, and most were of the germinal center type, while the present case
is the first report of a vimentin-positive primary Sp-DLBCL of the skull. The
DLBCL in this case was immunohistochemically stained for six representative
cytokines that might give rise to fibrosis, due to the evidence of fibroblastic
proliferation. The DLBCL cells were positive for platelet-derived growth factor
(PDGF), and some cells were also positive for tumor necrosis factor (TNF) alpha.
Based on these findings, it was inferred that the PDGF and TNFalpha produced by
DLBCL cells induced fibroblastic proliferation. The resultant conspicuous
fibrosis caused interfibrous impingement on the DLBCL cells, which deformed them
into a spindle shape. The present case is the first reported case of a PDGF
producing Sp-DLBCL.
PMID- 25120824
TI - A case of blastic plasmacytoid dendritic cell neoplasm with ecchymotic lesions on
the whole body.
AB - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) derived from plasmacytoid
dendritic cell precursors is a very rare, and characterized by cutaneous and bone
marrow involvement and leukemic spread. The neoplasm presents with an aggressive
behavior, and the clinical findings include cytopenia, particularly
thrombocytopenia. The tumor cells are negative for antigens of T- and B- cell
lines. However, these cells express CD4, CD56 and CD123, which are markers of
plasmacytoid dendritic cells, and negative for Epstein-Barr virus (EBV). From
this point of view, a 71-year-old man who was initially found to have a cutaneous
mass on his face and thorax was reported here, and initially was diagnosed as
"eczema". The skin rashes then became aggravated on a trial of low dose topical
corticosteroid for 2 months. According to skin biopsy, the tumor cells reveal an
immature blastic appearance and positive for CD4 and CD56, negative for CD3,
CD20, indicating a diagnosis of BPDCN. Here, we report the dismal course of a
patient with BPDCN without accepting further therapy, and only survived 3 months.
PMID- 25120825
TI - Plasmablastic lymphoma following combination treatment with fludarabine and
rituximab for nongastric mucosa-associated lymphoid tissue lymphoma: a case
report and review of literature.
AB - Plasmablastic lymphoma (PBL) is an uncommon malignancy which predominantly occurs
in the oral cavity of human immunodeficiency virus (HIV)-positive patients.
Sporadic cases have been published describing PBL in immunocompetent patients as
well as in immunodeficient patients following immunosuppressive therapy or
transplantation. We hereby reported a case of PBL in a 69-year-old, HIV-negative
male subjected to combination treatment with fludarabine and rituximab for
nongastric mucosa-associated lymphoid tissue (MALT) lymphoma. The diagnosis of
PBL was made with tumor cells of immunoblasts or plasmablasts morphology strongly
positive for MUM-1, EMA and CD138, and partly positive for CD38, and negative for
CD20, BCL-6, and CD56, and approximately 80% of which were positive for Ki-67.
The case presented PBL after MALT, and a history of chemotherapy including
fludarabine and rituximab led to the potential immunocompromised state. The
patient died 5 months after the diagnosis of PBL.
PMID- 25120826
TI - Mullerianosis and endosalpingiosis of the urinary bladder: report of two cases
with review of the literature.
AB - Mullerianosis of the urinary bladder is an extremely rare benign condition,
characterized by the presence of a mixture of at least two mullerian-derived
components, and endosalpingiosis is also an extremely rare condition,
characterized by the presence of tubal-type epithelium. In this report, we
describe the 17(th) case of mullerianosis and 5(th) case of endosalpingiosis of
the urinary bladder. A 39-year-old Japanese female presented with menstrual
hematuria and was found to have a polypoid lesion in the posterior wall of the
urinary bladder. Histopathological study demonstrated variably-sized dilated
tubular glands in the lamina propria and muscularis propria. These dilated glands
were covered by ciliated cuboidal cells, and some of them were covered by
columnar cells with intracytoplasmic mucin. Moreover, a tiny focus of endometrial
tissues was also present. Immunohistochemically, these glandular cells were
positive for estrogen receptor. Accordingly, a diagnosis of mullerianosis was
made. The second case was a 37-year-old Japanese female, who was found to have a
polypoid lesion in the posterior wall of the bladder. Dilated tubular glands were
covered by ciliated cells in the lamina propria and muscularis propria. Neither
endocervical nor endometrial tissues were observed. Immunohistochemically, these
ciliated cells were positive for estrogen receptor. Accordingly, a diagnosis of
endosalpingiosis was made. Our analysis revealed that these two conditions mainly
affect premenopausal females and occur exclusively in the posterior wall.
Although the pathogenesis remains completely unresolved, a metaplastic theory is
favored. The recognition of these two conditions is important because they can
mimic invasive adenocarcinoma.
PMID- 25120828
TI - Low-grade endometrioid carcinoma of the ovary associated with undifferentiated
carcinoma: case report and review of the literature.
AB - The association of low-grade endometrioid carcinoma with undifferentiated
carcinoma (UC) was first reported in endometrium carcinoma, termed with
dedifferentiated carcinoma (DC). However, the coexistence of low-grade
endometrioid carcinoma (LGEC) or serous carcinoma (LGSC) with UC has received
minimal attention in ovary, and the behavior of this kind of neoplasm remains at
further discussion. In this study, we reported a case of low-grade ovarian
endometrioid carcinoma associated with UC and reviewed another four cases
previously reported. We found a histological continuity between the LGEC and UC
components in H&E section, which suggested a dedifferentiation from LGEC to UC
components. In summary, this kind of pathological type has aggressive behavior
and these patients have very poor prognosis regardless of the amount of
undifferentiated carcinoma.
PMID- 25120827
TI - Ectopic cortisol-producing adrenocortical adenoma in the renal hilum:
histopathological features and steroidogenic enzyme profile.
AB - Ectopic cortisol-producing adrenocortical adenomas (CPA) are extremely rare, and
only four cases have previously been reported so far but the tumors were not
ultrastructurally studied. Presented in this paper is the fifth case with ectopic
CPA which was extensively examined to gain deeper insights in terms of the
histopathological features and steroidogenic enzyme profile of the tumor. A 53
year-old woman complained of accidental discovery of left renal mass. She had a 5
year history of hypertension, weight gain, moon face, thin skin and systemic
edema. These symptoms completely relieved after the tumor removal. Two years
later, the above symptoms recurred, and a recurrent tumor was revealed in left
renal hilum. The tumor was removed completely with relief of her symptoms of
Cushing's syndrome. Histologically and ultrastructurally, the tumor was composed
of compact cells and clear cells, and the former was prominent, suggesting an
active secretory function of the tumor. The adenoma tissue showed a strong
immunostaining for Melan-A, 3beta-hydroxysteroid dehydrogenase (HSD3B2) and
17alpha-hydroxylase1 (CYP17A1). Expression pattern for 11beta-hydroxylase 1
(CYP11B1), 11beta-hydroxylase 2 (CYP11B2), CYP17 and HSD3B2 mRNA in ectopic CPA
was similar to that in the adrenal CPA. In conclusion, in terms of
histopathological characteristic and steroidogenic enzyme profile, ectopic CPA is
similar to adrenal CPA, suggesting that they are of identical cell origin.
PMID- 25120829
TI - Sarcoidal granulomas in the mediastinal lymph nodes after treatment for marginal
zone lymphoma of the esophagus: report of a case with review of the concept of
the sarcoidosis-lymphoma syndrome.
AB - Patients with sarcoidosis have a high risk of development of malignant lymphoma,
and this association was coined the term "sarcoidosis-lymphoma syndrome".
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT
lymphoma) is a distinct clinicopathological entity, and the stomach is the most
common site. The occurrence of this type of lymphoma in the esophagus is
extremely rare. In this report, we describe the first documented case of
sarcoidal granulomas in the mediastinal lymph nodes after treatment for MALT
lymphoma of the esophagus. A 60-year-old Japanese female was found to have a
submucosal tumor in the esophagus. Histopathological study revealed proliferation
of small- to medium-sized lymphoid cells with convoluted nuclei, and
immunohistochemically, these lymphoid cells were diffusely positive for CD20, bcl
2, and MUM1. R-CHOP therapy was performed, which led to tumor remission. Two
years later, swelling of the mediastinal lymph nodes was detected.
Histopathological study of the lymph nodes revealed presence of variably-sized
epithelioid granulomas without caseating necrosis but no malignant lymphoma was
noted. Sarcoidal granulomas can be observed in patients with malignant tumors
including malignant lymphoma and carcinoma without history of systemic
sarcoidosis. It is important to recognize that systemic sarcoidosis and sarcoidal
reaction without evidence of systemic disease can occur after development of
malignant lymphoma, therefore, sarcoidal reaction must be included in the
differential diagnostic consideration of recurrent malignant lymphoma.
PMID- 25120830
TI - Posterior reversible encephalopathy syndrome in a child with steroid-resistant
nephrotic syndrome: a case report and review of literature.
AB - Posterior reversible encephalopathy syndrome (PRES) is a rare and serious
syndrome of central nervous system that can develop in both adults and children.
It is characterized by acute onset of headache, confusion, seizures or focal
neurological deficits along with radiological findings of white matter
abnormalities in the parietal and occipital lobes. In the past ten years, this
syndrome has been described mainly in adults, rare in children. Here, we report a
case of PRES presenting in a 12-year-old girl with steroid-resistant nephrotic
syndrome. Her neurological symptom was rapidly recovered after control of
hypertension without discontinuation of cyclosporine A.
PMID- 25120831
TI - A case of (123)I-MIBG scintigram-negative functioning pheochromocytoma:
immunohistochemical and molecular analysis with review of literature.
AB - A 70-year-old Japanese woman was referred to our hospital due to hyperhidrosis
and rapid weight loss of 10 kg in a month. A lump measuring 26 mm in diameter was
detected in the left adrenal gland by computed tomography. Biochemical tests
showed high levels of serum and urinary norepinephrine and epinephrine. However,
a (123)I-MIBG scintigram failed to detect any accumulation in the left adrenal
tumor. A left adrenalectomy was performed post clinical diagnosis of (123)I-MIBG
negative pheochromocytoma. Microscopically, the tumor exhibited pheochromocytoma
compatible features. Immunohistochemical analysis revealed low expression of
VMAT1 in the tumor compared to the normal, surrounding tissue. To test for a
possible genetic alteration of the monoamine transporter genes, we performed
whole-exome sequencing of the VMAT1, VMAT2, and NET genes in the tumor. No
significant base sequence substitution or deletion/insertion was found in any
transporter. This suggests that MIBG negativity is caused by a change that is
independent of the base sequence abnormalities, such as an epigenetic change.
Furthermore, a retrospective literature review of (123)I-MIBG negative
scintigraphy cases indicates that a negative finding in the (123)I-MIBG
scintigram is frequently associated with metastatic pheochromocytomas or SDHB
mutations. However, a SDHB/D gene mutation has not been identified in the
reported case. Although the patient needs careful monitoring following the
surgery, to date she has been disease free for 12 months. This study could not
find clear reasons for negative conversion, however, investigations of the
negative conversion mechanism might reveal significant insights towards the
improvement of patient survival.
PMID- 25120832
TI - Multiple genital tract tumors and mucinous adenocarcinoma of colon in a woman
with Peutz-Jeghers syndrome: a case report and review of literatures.
AB - We report a very rare case of Peutz-Jeghers syndrome (PJS) composed of multiple
genital tract tumors and mucinous adenocarcinoma. A 46-year-old woman presented
to our hospital with lower abdominal pain resulting from PJS involves sex cord
tumor with annular tubules (SCTAT), ovarian mucinous tumor, ovarian serous tumor,
mucinous adenocarcinoma of colon. The CEA concentration is high before surgery,
and decreases after the surgery and subsequent chemoradiotherapy. This case
demonstrates a classic clinical presentation of a patient with PJS. PJS patients
have increased risk of malignancy and early detection and regular surveillance of
the high-risk patients with PJS is crucial. Surgery may be required for
obstructive gastrointestinal lesions as well as those exhibiting malignant
degeneration.
PMID- 25120833
TI - Immunohistochemical results of HER2/neu protein expression assessed by rabbit
monoclonal antibodies SP3 and 4B5 in colorectal carcinomas.
AB - HER2/neu is an efficient target for cancer therapy. However, reports about its
overexpression rate in colorectal carcinomas showed wide variability. This study
aims to investigate HER2/neu expression in colorectal carcinomas using these two
rabbit monoclonal HER2/neu antibodies, and to clarify the relationship between
protein overexpression and gene amplification of HER2/neu and their
clinicopathologic importance. Tissue microarray was performed from sections of
106 cases colorectal carcinomas. Their clinical data, including gender, age,
stage, recurrence, lymph node metastasis, and follow-ups were collected.
Immunohistochemistry for rabbit monoclonal antibody SP3 and 4B5 were performed,
Fluorescent in situ hybridization was applied to detect the amplification of
HER2/neu gene. The HER2/neu overexpression of (2+ and 3+) in our results were
seen in 7.5% (8/106) for 4B5 and 3.8% (4/106) for SP3 respectively, the HER2/neu
amplification was in 2.8% (3/106). All cases of overexpression for SP3 were
included by those for 4B5. Both antibodies stained 3 cases of HER2/neu 3+, and
FISH confirmed HER2/neu amplification did occurred in these cases. In our study,
4B5 was more sensitive to detect HER2/neu of colorectal carcinoma than SP3. 2.8%
patients with colorectal patients might benefit from anti-HER2/neu therapy.
PMID- 25120834
TI - Malignant solitary fibrous tumor of breast: a rare case report.
AB - Solitary fibrous tumor (SFT) is rare mesenchymal neoplasm that has been
originally and most often documented in the pleura. Recently, the ubiquitous
nature of the SFT has been recognized with reports of involvement of numerous
sites all over the body such as: upper respiratory tract, somatic tissue,
mediastinum, head, and neck. Less than 10 cases SFT of breast have been reported.
Herein, we presented a 52-year-old Asian female with SFT of breast, this tumor
showed predominant malignant features. To our knowledge, SFT of breast with such
malignant evidence is extremely rare.
PMID- 25120835
TI - A case of lupus-like glomerulonephritis in an HIV patient with nephrotic range
proteinuria, purpura, and elevated IgA level.
AB - Human immunodeficiency virus (HIV) infection is growing medical concern
worldwide. There are many types of glomerulonephritis which are associated with
HIV infection. We report a case of a 53-year-old Korean man with an HIV
infection, who was developed nephritic range proteinuria and purpura with
elevated IgA level rasing a possibility of Henoch-Scholein Purpura (H-S purpura).
However, renal biopsy showed "lupus-like feature" glomerulonephritis without
clinical or serologic evidence of systemic lupus erythematosus. Although baseline
renal function was maintained without further need for maintenance dialysis
following anti-retroviral therapy (ART) and steroid, patient died from
uncontrolled gastrointestinal bleeding.
PMID- 25120836
TI - Mixed granular cell astrocytoma and fibrosarcoma of the brain: a case report.
AB - We describe a rare primary mixed granular cell astrocytoma and fibrosarcoma
neoplasm, occurring in a 52-year-old female, with morphologic,
immunohistochemical and molecular genetic features, whose tumor was entirely
composed of granular cells and fibrosarcoma competent. This represents, to the
best of our knowledge, the first report of the mixed granular cell astrocytoma
and fibrosarcoma neoplasm. Moreover, two parts forming a complex arrangement that
excluded it being assessed as a coincidental collision tumor. We discuss the
relationship of two parts of this rare tumor by fluorescence in situ
hybridization (FISH). Sarcomatous components in this tumor had the same
aberrations of chromosomes to the gliomatous components of neoplasms, consisting
of 1p 19q loss and no evidence of PTEN allele loss and amplification of EGFR. It
was suggested that the sarcomatous component may be derived from glioma cells i
this case.
PMID- 25120837
TI - Plasmablastic lasmablastic lymphoma of the duodenal and jejunum.
AB - Plasmablastic lymphoma (PBL) is a rare B-cell neoplasm with an aggressive
clinical behavior that predominantly occurs in the oral cavity of human
immunodeficiency virus (HIV)-positive patients. HIV-negative PBL has not been
extensively reported. A 65-year-old female presented with anemia, who was HIV
negative. Gastrointestinal fiberscope (GIF), and colon fiberscope (CF) were
performed. However, we could not detect the bleeding sites. We detected the tumor
by capsule endoscopy, and obtained the tumor cells from the duodenal and jejunal
sites. The neoplastic cells were diffusely positive for CD56, epithelial membrane
(EMA), CD4, lambda, and EBV-encoded RNA1 (EBER1) and partially positive for CD138
and CD79a. This patient was diagnosed as PBL. The small intestine is a rare extra
oral site of involvement in PBL patients, and only four cases in HIV-negative
patients have been reported.
PMID- 25120838
TI - Primary follicular lymphoma of the spleen incidentally found in a patient with
alcohol- and hepatitis C-related liver cirrhosis.
AB - Primary splenic lymphoma is rare as non-Hodgkin lymphomas. Splenic infiltration
of lymphoma cells may cause splenomegaly in many cases. However, splenomegaly is
caused not only by tumor involvement but also by non-tumorous disorders. One of
the most prevalent non-neoplastic causes is portal hypertension mostly due to
liver cirrhosis. On the other hand, liver cirrhosis may underlie various
extrahepatic manifestations including development of B-cell non-Hodgkin
lymphomas. Here, we report a case of primary follicular lymphoma of the spleen in
a patient with liver cirrhosis related to hepatitis C and alcohol. The lymphoma
was incidentally found in an enlarged spleen resected palliatively to alleviate
symptomatic pancytopenia of the patient. The main characteristic of our case is
an incidental finding of a rare situation brought by careful pathological
examination. Our case illustrates the importance to recognize a possibility of co
occurrence of chronic liver disease and extrahepatic lymphoma.
PMID- 25120839
TI - Sarcomatoid carcinoma involving the nasal cavity and paranasal sinus: a rare and
highly progressive tumor.
AB - Sarcomatoid carcinoma of nasal cavity and paranasal sinuses is an extremely rare
malignant neoplasm. We report a case of sarcomatoid carcinoma arising in the left
side nasal cavity and paranasal sinuses in a 65-year-old man who was hospitalized
for left-side nasal epistaxis, odor sensation. Histopathologic examination
revealed the tumor was composed of pleomorphic spindle and round cells with
frequent mitosis, and no carcinomatous component was recognized.
Immunohistochemistry revealed coexpression of cytokeratin and vimentin by the
tumor cells, whereas expressions of EMA, S-100, HMB-45, Melan-A, LCA, MyoD1,
CD34, CK7, F8 and desmin were negative. The diagnosis was sarcomatoid carcinoma
of nasal cavity and paranasal sinuses. The neoplasm was partial resected by nasal
endoscopic surgery following chemoradiation therapy immediately. But it was still
progressing rapidly, and had a poor prognosis.
PMID- 25120840
TI - Diagnostic problems related to acute fibrinous and organizing pneumonia:
misdiagnosis in 2 cases of lung consolidation and occupying lesions.
AB - Acute fibrinous and organizing pneumonia (AFOP) is a histological pattern
characterized by intra-alveolus fibrinous deposition accompanied with a spectrum
of clinical condition. It also presents in other types of lung lesions, thus
renders risks to its diagnosis with small biopsies. Here we present 2 cases of
lung consolidation and occupying lesions with typical histological presentation
of AFOP. One case is tuberculosis presented as massive lung consolidation,
initially treated as AFOP, and eventually progressed to bilateral military
tuberculosis. The other case presented an occupying mass in the lung which was
initially suspected to be an inflammatory mass with AFOP. Lobectomy revealed a
poorly-differentiated adenocarcinoma, with AFOP pattern present in the peripheral
tissues of the neoplastic mass. In conclusion, we suggest that it is not
preferable to diagnose idiopathic AFOP in lung consolidation and occupying
lesions before excluding other types of lesions. The diagnostic significance of
AFOP should be deliberated.
PMID- 25120841
TI - Blasts-more than meets the eye: evaluation of post-induction day 21 bone marrow
in CBFB rearranged acute leukemia.
AB - Induction chemotherapy is often the first therapeutic intervention for acute
myeloid leukemia (AML). Evaluation of post induction bone marrow provides
critical information for clinical management; in general increased blast countsor
increased marrow cellularity is an ominous sign, suggestive of ineffective
therapy, and may warrant additional rounds of chemotherapy. However, increased
blasts alone are not necessarily predictive of recurrent/persistent disease. Here
we report a very unusual observation in a case of AML with a core binding factor
beta (CBFB) rearrangement. In this case the day 21 post-induction marrow biopsy
showed a high blast count (approximately 20%), however,subsequent fluorescence in
situ hybridization studies were negative for CBFB rearrangement. We compared this
finding to post-induction marrows from a series of 6 AML cases with CBFB
rearrangements, none of which showed an increased blast count. This case
illustrates that increased blast counts, even those comprising 20% of cells, are
not de facto evidence of induction failure, and that correlation with ancillary
studies such as fluorescence in-situhybridization should be used to distinguish a
persistent neoplastic clone, from a brisk marrow recovery.
PMID- 25120842
TI - Intraneural malignant perineurioma: a case report and review of literature.
AB - The great majority of malignant peripheral nerve sheath tumors (MPNSTs) exhibit
Schwann differentiation. Few MPNSTs with perineurial differentiation are also
named malignant perineuriomas. Benign perineurioms were classified as
intraneural, extraneural (soft tissue), sclerosing, and reticular variant.
Histopathological features of intraneural perineurioma are individual nerve axons
surrounded by whorls of spindle-shaped cells arranged in an onion bulb-like
pattern. However, intraneural malignant perineurioma is uncommon, its
characteristic histological features were not clearly described yet. Positive for
epithelial membrane antigen (EMA), glut-1 and claudin-1, is characteristic of
malignant perineurioma. Herein, we report an intraneural malignant perineurioma
in median nerve of a 13-year-old girl. The clinicopathological features were
summarized and the related literatures were reviewed.
PMID- 25120843
TI - Membranous basal cell adenoma arising in the eyelid.
AB - Basal cell adenoma (BCA) is a specific entity that lacks the myxochondroid
stromal component of pleomorphic adenoma. Membranous basal cell adenoma is a rare
variant of BCA, which is characteristic by abundant eosinophilicextracellular
hyaline material deposited either inside or at the periphery of the epithelial
islands. Herin we describe the first case of membranous BCA arising in the upper
eyelid in a 38-year-old woman. A well-demarcated nodule arising in the eyelid was
composed of isomorphic basaloid cells organized with a prominent basal cell layer
and distinct basement membrane-like material. Immunohistochemically, S100 protein
and p63 highlighted the basal aspect of the peripheral epithelial cells, while
CK7 expressed on the luminal cells. A diagnosis of membranous basal cell adenoma
of the eyelid was made. At follow-up for 2 years and 3 months later, there was no
evidence of recurrence. Further pathological characteristics of this disease are
discussed.
PMID- 25120844
TI - Basal cell adenoma in the parotid: a bizarre myoepithelial-derived stroma rich
variant.
AB - Basal cell adenoma (BCA) is a specific entity that lacks the myxochondroid
stromal component of a pleomorphic adenoma. There are six histopathological types
of BCA: solid, tubular, trabecular, membranous, cribriform, and myoepithelial
derived stroma rich. Myoepithelial-derived stroma rich variant is so rare,
especially with cellular atypia. Herin we describe a rare case of BCA arising in
the parotid on a 25-year-old man. A well-demarcated nodule arising in the parotid
that was composed of basaloid cells, forming small duct-like or tubular
structures containing basement membrane-like material, as well as highly cellular
elongated cells with hyperchromatic, enlarged, pleomorphic, and bizarre nuclei.
Immunohistochemically, S100 protein and p63 highlighted the basal aspect of the
peripheral epithelial cells and peripheral spindle and bizarre cells, while CK7
expressed on the luminal cells. We made a diagnosis of "basal cell adenoma,
myoepithelial-derived stroma rich variant, with bizarre myoepithelial
proliferation". The differential diagnosis includes cellular pleomorphic adenoma,
basal cell adenocarcinoma, and carcinoma ex pleomorphic adenoma. After follow-up
for 3 years, there was no evidence of recurrence. Further pathological
characteristics of this disease are discussed.
PMID- 25120845
TI - Nasopharyngeal adenoid cystic carcinoma: a case report and review of the
literature.
AB - ACC derived from nasopharyngeal epithelial cells is rare, usually benign. In this
article, we reported a nasopharyngeal adenoid cystic carcinoma (NACC) in a 31
year-old woman with a symptom of hoarseness, headache, epistaxis slightly,
diplopia, facial numbness and dysphagia near 3 months. A tumor on the right side
of the nasopharynx was confirmed by laryngoscope check and MRI of the skull base.
Histopathological findings showed that tumor cells were arranged in cord-like or
acinar-like by atypical hyperplastic epithelial cells forming a cribriform and
tubular pattern, and immunohistochemical findings showed that tumor tissues were
immunopositive for p63 (+), CK7 (+), CK19 (+), CK8 (+), CK18 (+), SMA (+), CK
(+), p53 (++), S-100 (+) and Ki-67 (5%+), and negative for CD34 (-), CK5/6 (-),
CEA (-) and CD117 (-). Patient was treated by surgical operation and
radiotherapy, and was followed-up near 10 months, no local recurrence and distant
metastasis.
PMID- 25120846
TI - Successful treatment of recurrent Kimura's disease with radiotherapy: a case
report.
AB - Kimura's disease is a rare, chronic inflammatory disorder affecting the skin and
subcutaneous tissue, predominantly in the head and neck region. It is benign but
may be recurrent and difficult to eradicate. A case of recurrent Kimura disease
in a 53-year-old man was reported. Radiation therapy was performed for recurrence
after surgical excision twice. The prescribed radiation dose was 36 Gy. With a
follow-up time of 68 months, the patient was free of the disease.
PMID- 25120847
TI - Meningitis and pneumococcal pyomyositis in a child with intramuscular
hemangiomas: an autopsy case report.
AB - Pyomyositis is the bacterial infection of skeletal muscle, usually accompanied by
abscesses. The main etiologic agent is Staphylococcus aureus. There are rare
cases attributed to Streptococcus pneumoniae. This paper presents an autopsy of a
four year old child with multiple congenital intramuscular hemangiomas that
developed pneumococcal pyomyositis associated with meningitis. The authors
propose the hypothesis that patients with hemangiomas, mainly the intramuscular
type, may also represent a risk group for pyomyositis. The possibility of
respiratory/meningeal co-infection, might also be considered even if the clinical
picture is restricted to the muscular system.
PMID- 25120848
TI - Incidental finding of a giant asymptomatic right atrial tumor.
AB - Primary cardiac tumors are very rare, atrial myxoma being the most common benign
tumor of the heart. They may present with a great variety of incidental
asymptomatic masses to severe life-threatening cardiovascular complications
necessitating emergency surgery. Here we report the diagnostic evaluation and
successful surgical resection of such a giant cardiac tumor which was found on a
routine medical check-up in a 62-year-old patient. Histology confirmed diagnosis
of unusually huge myxoma. This article demonstrates it's necessary to include
cardiac tumors in the differential diagnosis of subtle and non-specific
cardiothoracic symptoms.
PMID- 25120849
TI - Expression of Gli1 and Wnt2B correlates with progression and clinical outcome of
pancreatic cancer.
AB - OBJECTIVE: The aim of this study was to investigate the expression and clinical
significance of Gli1 and Wnt2B in pancreatic cancer. METHODS: We have constructed
a formalin-fixed paraffin embedded pancreatic tissue microarrays 180 cylindrical
tissue cores of human pancreatic cancer and its paracancerous nonmalignant
pancreatic specimens (NMPs) from 90 patients. Levels of Gli1 and Wnt2B were
measured by immunohistochemistry. We analyzed the correlations between the
expression of these factors and clinicopathological parameters including
prognosis. RESULTS: The expressions of both Gli1 and Wnt2B in human pancreatic
cancer tissues were significantly higher than those of normal pancreatic tissues
(P=0.000, P=0.004 respectively). The analysis showed that the high cytoplasmic
expression levels of Gli1 in pancreatic cancer tissues had significant
correlation with lymph node metastasis (P=0.036) and Wnt2B had significant
correlation with perineural invasion (P=0.045). Gli1 and Wnt2B have no positive
correlation. Survival analysis by Kaplan-Meier demonstrated that elevated Wnt2B
expression in cancer tissue predicted worse overall survival (OS) compared with
group in lower expression (P=0.024). No correlation was found between the
expression of Gli1 and overall survival of pancreatic cancer patients (P>0.05).
CONCLUSIONS: In conclusion, these results indicate that the high-expression
levels of Gli1 and Wnt2B might play a pivotal role during tumorigenesis of
pancreatic cancer, and the high expression of Wnt2B might be associated with poor
prognosis.
PMID- 25120850
TI - Immunohistochemical expression of MPO, CD163 and VEGF in inflammatory cells in
acute respiratory distress syndrome: a case report.
AB - Acute respiratory distress syndrome (ARDS) is a serious medical condition
occurring in patients with polytrauma, pulmonary or non-pulmonary sepsis,
pneumonia and many other circumstances. It causes inflammation of the lung
parenchyma leading to impaired gas exchange with a systemic release of
inflammatory mediators, causing consequential lung tissue injury, hypoxemia and
frequently multiple organ failure. The aim of current study was to describe
expression of inflammatory markers (myeloperoxidase, CD163 and vascular
endothelial growth factor) by the cells in acute phase of ARDS. The lung samples
of a 20-year-old man who had suffered a serious motorbike accident were obtained
for histological examination. He died on the seventh day as a consequence of
respiratory failure. Our results imply that expression of CD163 was restricted to
activated alveolar macrophages and monocytes. Immunopositivityof MPO was observed
in neutrophil granulocytes within lung alveoli and lung blood vessels.
Myeloperoxidase positivity was observed in alveolar macrophages, too. Vascular
endothelial growth factor was expressed in cytoplasm of neutrophil granulocytes,
monocytes, small-sized alveolar macrophages and type II pneumocytes localized
mostly inside lung alveoli. On the contrary, no positivity was observed in lung
endothelial cells of blood vessels.
PMID- 25120851
TI - Clinicopathological and prognostic significance of microRNA-107 in human non
small cell lung cancer.
AB - BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNAs which can function as
oncogenes or tumor suppressor genes in human cancers. Researchers have found that
the expression level of miR-107 was decreased in human non-small cell lung cancer
(NSCLC) tissues and cell lines, however, its clinicopathological and prognostic
significance in NSCLC has not been investigated. METHODS: Quantitative real-time
PCR (qRT-PCR) was used to analyze the expression of miR-107 in 137 pairs of fresh
NSCLC and matched adjacent normal tissue specimens. The chi-square test and
Fishers exact tests were used to examine the associations between miR-107
expression and the clinicopathological characters. The overall survival (OS) and
progression-free survival (PFS) were analyzed by log-rank test, and survival
curves were plotted according to Kaplan-Meier. RESULTS: The expression level of
miR-107 was significantly lower in tumor tissues than that in corresponding
noncancerous tissues (0.4676 +/- 0.2078 vs. 1.000 +/- 0.3953, P<0.001). Low
expression of miR-107 was found to significantly correlate with TNM stage
(p=0.001), regional lymph node involvement (p=0.04), and tumor differentiation
(p=0.003). Kaplan-Meier analysis with the log-rank test indicated that low miR
107 expression had a significant impact on OS (35.2% vs. 69.3%; P=0.008) and PFS
(30.0% vs. 56.2%; P=0.029). In a multivariate Cox model, we found that miR-107
expression was an independent poor prognostic factor for both 5-year OS (HR=2.57,
95% CI: 1.88-10.28; P=0.007) and 5-year PFS (HR=3.08, 95% CI: 2.01-8.92;
P=0.003). CONCLUSION: The expression of miR-107 was decreased in NSCLC. Low
expression of miR-107 was significantly associated with tumor progression and
decreased survival in patients with NSCLC, indicating that miR-107 may serve as a
novel prognostic marker in NSCLC.
PMID- 25120853
TI - [Factors associated with infection in rheumatoid arthritis].
PMID- 25120852
TI - Inosine triphosphate pyrophosphohydrolase (ITPA) polymorphic sequence variants in
Chinese ALL children and possible association with mercaptopurine related
toxicity.
AB - Genetic polymorphisms are important factors in effects and toxicity of
chemotherapeutics. This study aimed to investigate whether there was a
correlation between genotype or haplotype of inosine triphosph
pyrophosphohydrolase(ITPA) and toxicities during maintenance therapy with
mercaptopurine (6-MP) in Chinese patients with acute lymphoblastic leukemia
(ALL). 95 ALL children who hospitalized between October 2004 and September
2007,were retrospectively analyzed. 6-MP toxicity was documented according to
Common Toxicity Criteria, Version 2.0. ITPA sequencing was undertaken.
Correlation between genotype/haplotype and 6-MP toxicity was analyzed. The
results indicated that 50 cases (52.6%) had grade III-IV of bone marrow
inhibition. These children had long-term disease-free survival (DFS), without
hepatic and other organs' dysfunction and secondary tumors. Three variations were
observed in ITPA exon 2 (94 C -> A), exon 3 (138 G -> A), and exon 8 (561 G ->
A), the 94A carriers (CA and AA) had a lower risk of developing 6-MP toxicity
when compared with carriers of the CC genotype (odds ratio [OR] 0.34, 95%
confidence interval [CI] 0.12-0.98, P = 0.039). The risk of 6-MP intolerance was
decreased in patients with 138 allele and 561 allele polymorphism, but with no
significant difference. Patients carrying the haplotype 94A-138A-561A was
tolerance compared to those with wild-type haplotype 94C-138G-561G (OR: 0.26, 95%
CI 0.07-0.94 P = 0.043). In conclusion, the risk of 6-MP intolerance was
decreased in patients with 138 allele and 561 allele polymorphism, but without
significant difference. Patients carrying the haplotype 94A-138A-561A was
tolerance compared to those with the wild-type haplotype 94C-138G-561G.
PMID- 25120854
TI - [Epidemiology and management of intrapartum infections in the maternity ward of
Oueme-Plateau county hospital in Benin].
PMID- 25120855
TI - Providing medical care in unfamiliar settings; experience of an Egyptian campaign
in Uganda.
AB - Medical service in many African countries is affected by the limited
infrastructure and the lack of economic and human potentials. Uganda is one the
countries that suffers from lack of physicians as well as shortage of many
medical facilities with many endemic health problems such as Goiter. A surgical
camp was done by an Egyptian team of 8 physicians; three general surgeons, one
pediatric surgeon, two gynecologists and one anesthetist. Over two hundred cases
were screened in the outpatient clinic. Eighty nine operations were done in four
days. General surgery procedures were 45 operations (50%), Pediatric procedures
were 23 operations (26%) and Gynecological operations were 21 operations (24%) In
conclusion Humanitarian relief for poor population in the developing world
countries needs vigilant international collaboration. Special attention should be
given to goiter in African countries. Training doctors from sub-Saharan African
nations should be on the top of the agenda of the international medical community
in order to reach a definitive solution for their health problems.
PMID- 25120856
TI - Giant brain tuberculoma mimicking a malignant tumor in a child.
PMID- 25120857
TI - Fracture of the bamboo spine (chronic ankylosing spondylitis) after cervical
injury.
PMID- 25120858
TI - [Eyelid S-shape deformation revealing a pleomorphic adenoma].
PMID- 25120859
TI - Effect of body composition on bone mineral density in Moroccan patients with
juvenile idiopathic arthritis.
AB - INTRODUCTION: The link between bone mass and body composition is widely
recognized, but only few works were selectively performed on subjects with
juvenile idiopathic arthritis. The aim of our study was to investigate the effect
of body composition on bone mineral density (BMD) in Moroccan patients with
juvenile idiopathic arthritis. METHODS: Thirty three children with juvenile
idiopathic arthritis (JIA) were included in a cross-sectional study. The
diagnosis of JIA was made according to the criteria of the International League
of Association of Rheumatology (ILAR). Body mass index (BMI) was calculated from
the ratio of weight/height(2)(kg/m(2)). Pubertal status was determined according
to the Tanner criteria. Bone status, body composition and bone mineral content
(BMC) were analyzed by using dual-energy X-ray absorptiometry (DXA). BMD was
assessed at the lumbar spine (L1-L4) and at total body in (g/cm(2)). Total body
fat tissue mass (FTM) and lean tissue mass (LTM) were also analyzed by DXA and
expressed in kilograms. In children, low BMD was defined as a Z-score less than
2 and osteoporosis was defined as a Z-score less than -2 with a fracture history.
RESULTS: A cross-sectional study was conducted in 33 Moroccan patients with JIA
aged between 4 and 16 years, Fat mass was not related to bone density; in
contrast, BMD was positively associated to LTM in total body(r = =0.41, p= 0.04)
but not in lumbar spine (r = 0.29, p= 0.17). There exist significant correlation
between BMC and BMD in total body (r = 0.51, p = 0.01). CONCLUSION: This study
suggests that the LTM is a determining factor of the BMD during adolescence.
Other studies with a broader sample would be useful to confirm this relation.
PMID- 25120860
TI - Pattern of cardiovascular admissions at Nnamdi Azikiwe University Teaching
Hospital Nnewi, South East Nigeria.
AB - INTRODUCTION: Cardiovascular disease (CVD) is one of the top killer diseases in
the world sparing neither developed or developing countries. The study was
carried out to determine the pattern of cardiovascular admissions at Nnamdi
Azikiwe University Teaching Hospital Nnewi South East Nigeria. METHODS: The study
was a retrospective study covering the period January 2007 to December 2009. SPSS
version 13 software was used to analyze data. RESULTS: 537 (15%) patients were
admitted into the study out of 3546 patients {females 1756 and 1790} admitted
into medical wards. 322 (60%) of study population were males and 215 (40%)
females. 359(67.5%) were discharged, 170 (32%) died and 8 (0.5%) were discharged
against medical advice. The majority of the deaths 105(61.8%), were in patients
with CVA. Most of the deaths (111 or 65.3%) occurred within the first seven days
of admission. The mean age of the population was 60.7 years +/-15.9 with a range
of 18 to 110 years. The length of stay in hospital ranged between 1 and 140 days
with a mean of 13.5 +/- 13.9 days and a median of 10 days. 33 of the subjects
were single, 406 were married, 94 were widowed (11 males and 83 females) and 4
were divorced. 46.7% (251) were admitted for CVA and 30.9% (166) for heart
failure. Cardiomyopathy/valvular heart diseases (clinical diagnosis due to
absence of echocardiography) constituted 3.9%, hypertension 20.5% and pre
existing hypertension with uremia 1.9%. CONCLUSION: The study has shown that
cardiovascular disease contributed significantly to medical admissions the
elderly accounting for a significant proportion. There is thus the need for
intensification of primary preventive strategies for cardiovascular diseases.
PMID- 25120861
TI - [Epidemiological profile of primary malignant tumors of the salivary glands:
about 154 cases].
PMID- 25120862
TI - [Esophageal involvement during pemphigus vulgaris].
PMID- 25120863
TI - [Rectal stromal tumor: report of a case].
PMID- 25120864
TI - Painless extensive ossification of the Achilles tendon: a diagnostic trap?
PMID- 25120865
TI - [Occipital tumors: a medical or surgical emergency?].
PMID- 25120867
TI - [Pre-renal mass of adrenal origin: what is your diagnosis?].
PMID- 25120866
TI - First results of hormone receptors' status in Malagasy women with invasive breast
cancer.
AB - INTRODUCTION: Breast cancer is the most common malignancy tumor amongst Malagasy
women registered at the pathology unit of the "Institut Pasteur de Madagascar".
In Madagascar, there is no laboratory practicing hormone receptors' status on
these tumors. Until now no study about hormone receptors' status of Malagasy
women with invasive breast cancer was performed. So it will be the first study
talking about this topic. The aim of this study was to determine hormone
receptors' status in Malagasy women with invasive breast cancer. METHODS: This
retrospective and descriptive study was based on patients' medical files from
2009 to 2011. It included all invasive breast cancer diagnosed in Malagasy women
at the pathology laboratory located at the "Institut Pasteur de Madagascar", in
Antananarivo. Along this period this laboratory has sent paraffin blocks of
invasive breast carcinoma in two pathological laboratories in France. RESULTS: We
collected 77 cases of invasive breast cancer along this period. The mean age was
48.8 +/- 10.7, ranging from 26 years to 70 years. There were 46.8 % (n = 36)
women with progesterone receptor positive (PR+), 53.2 % (n = 41) with
progesterone receptor negative (PR-). For the estrogen receptor, 61.0 % (n = 47)
were positive and 36.4 % (n = 28) were negative. ER+/PR+ represented 44.2 % (n =
34); ER-/PR- 33.8 % (n = 26); ER +/ PR- 16.8 % (n = 13); ER-/PR+ and ER-/PR-
represented respectively 2.6 % (n = 2). CONCLUSION: Patients in our study had
more important rate of ER-, PR- and a less important rate of ER+/PR+, PR+. These
results suggest that more study related to Hormone Receptor profile should be
conducted in Malagasy women with breast cancer.
PMID- 25120869
TI - [Heart with six cavities in a 11-year old child].
PMID- 25120868
TI - Tobacco control research in Kenya: the existing body of knowledge.
AB - This review examines the existing tobacco control research done in the country.
It further identifies key gaps present in research and gives recommendations on
priority research areas required to implement effective tobacco control
programmes. Published literature, technical reports and reports by the Ministry
of Health were reviewed. It included studies that measure tobacco use and its
effects, monitor progress of tobacco control, or articles that are discussing
tobacco control policy. The review was conducted in January 2013 and included 18
papers. There are six studies that assessed the prevalence of current tobacco
consumption which yielded prevalence's of between 3.8%-19%. Only one study tried
to determine an association between Tobacco use and Health. Studies that
monitored progress of legislation indicated that the country lacked coordinated
efforts for tobacco control, enforcement was weak and monitoring of the existing
tobacco legislation was poor. This review has demonstrated that Kenya has made
efforts to generate knowledge on tobacco control through research. However there
is lack of research that demonstrates the effects of tobacco consumption on
health and studies that detail the impact of the various tobacco control
interventions.
PMID- 25120870
TI - A tuberculosis case mimicking lymphoma.
AB - Tuberculosis remains a worldwide health problem causing morbidity and mortality.
Abdominal tuberculosis is a rare form of the disease. Abdominal form of
tuberculosis can mimic other non-infectious diseases. In this report, we
presented an abdominal tuberculosis presenting with an intra-abdominal mass
lesion and multiple lymphadenopathies that mimics lymphoma.
PMID- 25120871
TI - Late onset epilepsy associated with marijuana abuse: a case report with MRI
findings.
AB - Marijuana is the most widely used illicit substance in the world. The relation
between marijuana use and epileptic seizures is still controversial. We report a
case of late onset epilepsy associated with marijuana abuse, with brain magnetic
resonance imaging (MRI) findings. A 44-year-old patient was admitted for 03
isolated episodes of secondary generalized tonic-clonic seizures. He had a
history of 26 years regular marijuana smoking. On admission, we found a
tachycardia, psychomotor slowing, asymmetric hyperreflexia, bilateral Babinski
sign without weakness. Laboratory work-up showed a high level of urine of Delta-9
tetrahydroxycannabinol. Electroencephalogram was normal. Brain MRI revealed
abnormal signal intensities in the right frontal lobe and basal ganglia. Seizures
cessation was obtained with anti-epileptic treatment. We suggest that marijuana
abuse through vascular and toxic mechanisms could explain seizures in this case.
PMID- 25120872
TI - [Colobomatous cyst of the orbit].
PMID- 25120873
TI - [Critical study of the treatment of 159 elderly in psychiatric consultation].
PMID- 25120874
TI - Family and socioeconomic risk factors for undernutrition among children aged 6 to
23 Months in Ibadan, Nigeria.
AB - INTRODUCTION: Child undernutrition is a major public health problem in Nigeria
and other Sub-Saharan African countries. However, few analytical studies have
quantified the role of risk factors. This study was conducted to determine the
socio-economic and family related risk factors for undernutrition among children
in Ibadan, Nigeria. METHODS: A case-control study was conducted among children
100 cases and 200 controls aged 6-23 months. A semi-structured interviewer-
administered questionnaire was used to obtain information on socio-economic
status, infant feeding practices of the mothers, children's immunization status
and recent episodes of common childhood illnesses. Bivariate and multivariate
analyses were conducted to identify the risk factors. RESULTS: On bivariate
analysis, the maternal factors associated with undernutrition were maternal level
of education below secondary level, monthly income below $20 and polygamous
marriage. Socio-economic factors significantly associated with malnutrition were
residence in a high density area, family accommodation in a single room apartment
and family weekly expenditure on food below $55. Children's characteristics
associated with child malnutrition included incomplete immunization for age,
recent episodes of diarrhoea and acute respiratory infection. The significant
risk factors on multivariate analysis were maternal monthly income <$20, monthly
household food expenditure <$55, residence in a one room apartment, higher birth
order and incomplete immunization of the child. CONCLUSION: The multiplicity of
risk factors identified is indicative of the need for a multidisciplinary
approach in developing preventive strategies child undernutrition.
PMID- 25120875
TI - [Sirenomelia (Mermaid syndrome): description of the first Congolese cases and
review of the literature].
PMID- 25120876
TI - [Cholesteatoma of the middle ear - retrospective study about 145 cases].
PMID- 25120877
TI - [Esophagitis dissecans: a rare cause of dysphagia].
PMID- 25120878
TI - [Gouty tophi of the hand revealing a gout].
PMID- 25120879
TI - [Tuberculous tenosynovitis of the extensors of the hand: a rare localization of
tuberculosis].
PMID- 25120880
TI - [Ophthalmic zoster of th eyelid: good outcome with valaciclovir].
PMID- 25120881
TI - Forestier's disease presenting with dysphagia and disphonia.
AB - Forestier's disease, also known as diffuse idiopathic skeletal hyperostosis
(DISH), is a pathology of vertebral bodies characterised by exuberant osteophytis
formation. Forestier's disease is usually managed conservatively. Surgical
resection of the osteophytes is reported to be an effective treatment for severe
cases and/ or cases with airway obstruction. We report a 55-year-old man
presenting with 6 months' progressive dysphagia and dysphonia. He was managed
successfully with an anterior cervical osteophytectomy without fusion. A
literature review is included.
PMID- 25120882
TI - Unusual presentation of hepatocellular carcinoma invading the anterior abdominal
wall muscles.
AB - Hepatocellular carcinoma (HCC) is a common cancer all over the world. It
demonstrates a tendency for vascular invasion, producing extensive intrahepatic
metastases and portal vein or inferior vena cava extension. Tumor spread of
abdominal diseases via hepatic ligaments has also been reported. The author
reports a rare case of HCC invading the anterior abdominal wall muscles and
protruding into the subcutaneous fat.
PMID- 25120883
TI - Intramuscular lipoma: infiltrating vs. well-circumscribed variant.
PMID- 25120884
TI - [Contribution of imaging in the diagnosis of infectious sacroiliitis: about 19
cases].
PMID- 25120885
TI - [Bladder exstrophy: about a case diagnosed tardily].
PMID- 25120887
TI - Effects of disadvantage in early life on cardiometabolic health status in
adulthood.
PMID- 25120886
TI - Effects of Nrf2 deficiency on bone microarchitecture in an experimental model of
osteoporosis.
AB - OBJECTIVE: Redox imbalance contributes to bone fragility. We have evaluated the
in vivo role of nuclear factor erythroid derived 2-related factor-2 (Nrf2), an
important regulator of cellular responses to oxidative stress, in bone metabolism
using a model of postmenopausal osteoporosis. METHODS: Ovariectomy was performed
in both wild-type and mice deficient in Nrf2 (Nrf2(-/-)). Bone microarchitecture
was analyzed by MUCT. Serum markers of bone metabolism were also measured.
Reactive oxygen species production was determined using dihydrorhodamine 123.
RESULTS: Sham-operated or ovariectomized Nrf2(-/-) mice exhibit a loss in
trabecular bone mineral density in femur, accompanied by a reduction in cortical
area in vertebrae. Nrf2 deficiency tended to increase osteoblastic markers and
significantly enhanced osteoclastic markers in sham-operated animals indicating
an increased bone turnover with a main effect on bone resorption. We have also
shown an increased production of oxidative stress in bone marrow-derived cells
from sham-operated or ovariectomized Nrf2(-/-) mice and a higher responsiveness
of bone marrow-derived cells to osteoclastogenic stimuli in vitro. CONCLUSION: We
have demonstrated in vivo a key role of Nrf2 in the maintenance of bone
microarchitecture.
PMID- 25120888
TI - Binge drinking and its relation to metabolic syndrome in korean adult men.
AB - BACKGROUND: It is reported that heavy drinking increases the risk of metabolic
syndrome. But there have been few studies on the relationship between the
intensity of drinking and metabolic syndrome when drinking the same amount of
alcohol. This study aimed to assess the relationship between the frequency of
binge drinking and metabolic syndrome in Korean adult men. METHODS: From the
database of the 4th and 5th Korea National Health and Nutrition Examination
Survey conducted in 2007-2010, data of 8,305 adult men (>=19 years of age) was
included in this analysis. Cross-sectional relationship between the frequency of
binge drinking and metabolic syndrome was investigated adjusting for pure alcohol
consumed per day. RESULTS: Adjusting for various confounders including pure
alcohol consumed per day, the adjusted odds ratio for metabolic syndrome in those
in higher frequency (more than 1/wk) binge drinking group was 1.62 (95%
confidence interval, 1.30 to 2.03; P for trend = <0.001) compared to those in the
non-binge drinking group. Through analysis of the relationship between pure
alcohol consumed per day and metabolic syndrome, it was found that pure alcohol
consumed per day had a positive relation to metabolic syndrome in the higher
frequency binge drinking group (P for trend = 0.041). The relationship was
inverse in the non-binge drinking group (P for trend = 0.002). CONCLUSION: Our
study found a positive relationship between frequency of binge drinking and
metabolic syndrome in adult men. And the effect of drinking on metabolic syndrome
may depend on the frequency of binge drinking. Further studies are required to
confirm this association.
PMID- 25120889
TI - Association between Appendicular Fat Mass and Metabolic Risk Factors.
AB - BACKGROUND: Different regional fat depots have different effects on lipid and
glucose metabolism. The purpose of this study is to examine the relationship
between body fat distribution as measured by dual-energy X-ray absorptiometry
(DEXA) and metabolic risk factors and to disclose whether there is any difference
between groups with and without metabolic syndrome (MS). METHODS: A total of 292
participants (98 men, 194 women) over 19 years old underwent whole-body DEXA to
evaluate body composition with respect to the whole body, leg, arm, and android
regions. Anthropometry and blood tests for metabolic risks were measured.
RESULTS: One hundred and seven participants were diagnosed with MS. The MS group
had significantly higher android fat (%) and had lower leg fat (%), arm fat (%),
and appendicular (arms + legs) fat (%) than the non-MS group. Android fat (%) had
a positive correlation with waist circumference (WC), systolic blood pressure
(SBP), diastolic blood pressure (DBP), glucose, log insulin, hemoglobin A1c
(HbA1c), triglyceride (TG), and low density lipoprotein cholesterol, and had a
negative correlation with high density lipoprotein (HDL) cholesterol.
Appendicular fat (%) had a negative correlation with WC, SBP, DBP, glucose, log
insulin, HbA1c, and TG, and had a positive correlation with HDL cholesterol. The
association of appendicular fat with metabolic risk was consistently observed in
non-MS, but the association was not observed except for SBP, glucose and log
insulin in MS. CONCLUSION: In contrast with the adverse effects of android fat,
appendicular fat distribution was associated with decreased risks of MS. The
protective effect of appendicular fat against metabolic risk factors in non-MS
was less characteristic in MS.
PMID- 25120891
TI - Pro Re Nata Prescription and Perception Difference between Doctors and Nurses.
AB - BACKGROUND: Pro re nata (PRN) prescription is a frequently used prescription
method in hospitals. This study was conducted to investigate actual condition of
PRN prescription and whether administration error occurred because of perception
difference between doctors and nurses. METHODS: From May to July 2012, a survey
was conducted among 746 doctors and nurses (88 doctors and 658 nurses) working at
5 hospitals located in Seoul, Gyeong-gi, and Gangwon Province. Doctors generating
PRN prescription responded to actual conditions of PRN prescription and both
doctors and nurses reported whether administration error occurred due to
perception difference. RESULTS: Average number of PRN prescription of surgical
residents was 4.6 +/- 5.4, which was larger than that of medical residents (1.7
+/- 1.0). Surgical residents more frequently recorded maximum number of daily
intake (P = 0.034) and, although not statistically significant, more often wrote
exact single dosage (P = 0.053) and maximum dosage per day (P = 0.333) than
medical residents. Doctors expected nurses to notify them before the
administration of medication; however, nurses were more likely to conduct PRN
administration by their own decision without informing doctors. In addition, some
doctors and nurses experienced administration errors because of it. CONCLUSION:
Standard prescription methods need to be established since there is a perception
difference in PRN prescription between doctors and nurses and this could be
related to administration errors.
PMID- 25120890
TI - Association between Nutrition Label Reading and Nutrient Intake in Korean Adults:
Korea National Health and Nutritional Examination Survey, 2007-2009 (KNHANES IV).
AB - BACKGROUND: Nutrition labels provide various information on the nutrient contents
of food. However, despite the recent increase in the interest in dietary intake
and expansion of related policies, studies on the association between nutrition
label reading and dietary intake are lacking in Korea. METHODS: This study
analyzed the 2007-2009 KNHANES (Korean National Health and Nutrition Examination
Survey) data. To examine macronutrients and micronutrients intake according to
nutrition label reading, analysis of covariance was used. Multiple logistic
regression analysis was also used to examine the association between adherence to
dietary reference intake and nutrition label reading. RESULTS: Nutrition label
reading was significantly high among women, youth, and those with high education
and high household income. Nutrition label reading was associated with higher
intake of calcium and vitamin C in men and the lower intake of calorie,
carbohydrates and higher energy ratio of protein in women. Additionally, male
nutrition label readers were associated with adherence to dietary reference
intake of fiber (odds ratio [OR], 2.00; 95% confidence interval [CI], 1.23 to
3.26) and calcium (OR, 1.26; 95% CI, 1.03 to 1.54). In women, there were no
significant differences in the adherence to the dietary reference intake in fat,
fiber, sodium, potassium, and calcium according to the nutrition label reading.
CONCLUSION: In men, nutrition label reading was associated with healthier intake
of several micronutrients, although this was not observed in women. Consideration
for clearly reporting vulnerable micronutrients in nutrition labels is necessary.
PMID- 25120892
TI - The Relationship between Metabolic Syndrome and Childhood Maternal Education
Level, Job Status Findings from the Korean National Health and Nutrition
Examination, 2007-2009.
AB - BACKGROUND: Childhood socioeconomic status (SES) is known to affect cardio
metabolic disease risk. However, the relationship between childhood SES and
metabolic syndrome (MetS) remains uncertain. Therefore, we investigated the
relationship between childhood SES, as measured by maternal education and
occupational status and adult-onset MetS in the Korean population. METHODS: We
examined the association between childhood SES, as measured by maternal education
level and occupational status during an individual's childhood, and MetS in
Korean adults aged 20 to 79 years who participated in the 2007-2009 Korean
National Health Examination and Nutrition Survey. The components of MetS,
including waist circumference, fasting glucose, lipid profiles, and blood
pressure, were measured. Adjusted odds ratios (ORs) for MetS were calculated
using multiple logistic regression models. RESULTS: Significant differences in
the association between maternal education level, occupational status, and MetS
were found between males and females. In females, the adjusted MetS OR for the
highest maternal education quartile relative to the lowest quartile was 0.46
(0.21-0.99). Similarly, in females, the adjusted OR for individuals whose mothers
worked when they were children relative to those whose mothers did not work was
1.23 (1.04-1.44). In males, no significant associations between maternal
education, maternal occupational status, and MetS were found. CONCLUSION: We
found independent, positive associations between maternal education and
occupational status and MetS in Korean females. These findings suggest that
public health education targeting MetS prevention should be considered,
especially among children with less opportunity for maternal support.
PMID- 25120893
TI - Gluten-free diet and quality of life in celiac disease.
AB - Many recent studies overshadow the effects of gluten-free diet. Gluten-free diet
positive effects were observed in celiac disease patients: increase in body mass
index, higher energy intakes, reducing adiposity gain, moderates the risk of the
associated complications. However, adhering to a gluten-free diet is difficult
for many people. A new solution is needed for quality of life of celiac disease
patients, not for celiac disease treatment. Health education on gluten-free diet
at home and in society seems to be the solution. The aim of our study is to
evaluate the recent research on gluten-free diet as a nutritional therapy for
patients with celiac disease. To achieve this purpose we have analyzed the
published studies from 2008 to the present on nutrition in celiac disease.
PMID- 25120894
TI - Prevalence of hepatitis D virus in hepatitis B virus infected patients referred
to Taleghani hospital, Tehran, Iran.
AB - AIM: The aim of this study was to determine the prevalence of HDV infection
between HBV chronic patients referred to gastroenterology ward of Taleghani
hospital Tehran, Iran and also investigating the risk factors in acquiring the
HDV infection. BACKGROUND: Hepatitis B virus (HBV) and Hepatitis D virus (HDV)
are major public health issues. Worldwide there are approximately 350 million
individuals chronically infected with the HBV. A significant part of them,
including 15 to 20 million coinfected with HDV. Hepatitis Delta virus is
transferred mostly through blood and body fluids. PATIENTS AND METHODS: HBV and
HDV infections were evaluated by Enzyme-linked immunosorbent assay (ELISA). Liver
functional tests were assessed through auto analyzer. Patients were interviewed
and data along the test results were entered into SPSS program. We used chi
square, independent t-test and logistic regression for statistical analysis.
RESULTS: 278 (54.6%) patients of the study group were male and 231 (45.4%) were
female and the mean age of patients was 40.03 +/- 14.93. From 509 patients,
39(7.7%) had anti-HDV antibody. In a uni-variable analysis, age (p=0.001),
periodontal procedures (p=0.015), endoscopy (p=0.024) and colonoscopy (p=0.012)
were significantly related to HDV seropositivity. After adjustment by logistic
regression, age remained the only significant factor in acquiring HDV infection.
CONCLUSION: We highly recommend the health care workers to strictly follow the
disinfection protocols of medical instruments. Since HDV seroprevalence changes
over time, regular epidemiological studies are necessary to monitor the
epidemiological trend of infection.
PMID- 25120895
TI - Comparison of half-dose and full-dose triple therapy regimens for Helicobacter
pylori eradication in patients with end-stage renal disease.
AB - AIM: The aim of this study was to compare the half-dose and full-dose triple
therapy regimens for Helicobacter pylori (Hp) eradication in patients with end
stage renal disease. BACKGROUND: H. Pylori is one the most important causes of
dyspepsia in patients with end-stage renal disease (ESRD). PATIENTS AND METHODS:
Sixty-six patients with ESRD were enrolled in the study with Hp infection and
peptic disease with a need of Hp eradication. Patients were randomly assigned to
full-dose (A=35 patients) or half-dose group (B=31 patients). Patients received
clarithromycin 500 mg, amoxicillin 1000 mg and omeprazole 20 mg twice daily in
group A and clarithromycin 250 mg and amoxicillin 500 mg twice daily and
omeprazole 20 mg once daily in group B for two weeks. Patients provided stool
samples 4 weeks of completing study to assess the success of Hp eradication by Hp
specific stool antigen. Finally, the rate of eradication and complications were
compared between two groups. RESULTS: The successful Hp eradication was achieved
in 26 patients (74%) in group A and in 22 patients (74%) in group B. The
difference between 2 groups was not statistically significant (p=0.973) (per
protocol analysis). CONCLUSION: Half-dose triple-therapy with clarithromycin,
amoxicillin and omeprazole is as effective as full-dose triple-therapy to
eradicate the Hp in patients with ESRD. According to lower toxicity level,
complications and cost in half-dose regimen in this subset of patients, this
protocol is advised.
PMID- 25120896
TI - The efficacy of a synbiotic containing Bacillus Coagulans in treatment of
irritable bowel syndrome: a randomized placebo-controlled trial.
AB - AIM: We aimed to evaluate the efficacy of a synbiotic containing Bacillus
Coagulans in treatment of IBS. BACKGROUND: Some studies have shown the efficacy
of probiotics in the treatment of irritable bowel syndrome (IBS). PATIENTS AND
METHODS: Adult IBS patients (n=85) were randomized to receive a synbiotic
containing Bacillus Coagulans or placebo for 12 weeks. Frequency of IBS symptoms
including abdominal pain (scored 1 to 7), and diarrhea and constipation (scored 1
to 5) was evaluated before and after the intervention and then after nine months
follow-up. RESULTS: Twenty-three patients in the synbiotic group and 33 patients
in the placebo group completed the study (age = 39.8+/-12.7 years, 78.6% female).
After treatment, more reduction in abdominal pain frequency was observed with
synbiotic compared with placebo (score reduction 4.2+/-1.8 vs. 1.9+/-1.5,
P<0.001). Diarrhea frequency was decreased in the synbiotic group, but not in the
placebo group (score reduction 1.9+/-1.2 vs. 0.0+/-0.5, P<0.001). Decrease in
constipation frequency was the same between the two groups (score reduction 0.9+/
1.2 vs. 0.8+/-1.1, P=0.561). After nine months follow-up, abdominal pain
frequency was decreased (P=0.016), constipation frequency was increased
(P<0.001), and diarrhea frequency remained unchanged in the synbiotic group
(P=1.000). In the placebo group, abdominal pain frequency was increased
(P<0.001), constipation frequency remained unchanged (P=0.553), and diarrhea
frequency was increased (P<0.001). CONCLUSION: Bacillus Coagulans improves
abdominal pain and diarrhea in IBS patients. Further studies on a larger sample
of patients are warranted.
PMID- 25120898
TI - Molecular identification of Giardia lamblia; is there any correlation between
diarrhea and genotyping in Iranian population?
AB - AIM: The aim of this study is to investigate the molecular identification of
Giardia lamblia in patients with diarrhea. BACKGROUND: Giardiasis caused by
Giardia lamblia is a common intestinal disease. Although this parasitic infection
found in mammals including human, pets and livestock, but few species within the
genus Giardia can infects humans. G. lamblia have seven complex genotypes termed
(A-H). Genotype A and B the main causes of human infections. PATIENTS AND
METHODS: Sixty seven microscopically positive G. Lamblia samples were collected
from clinical laboratories in Isfahan province between June 2013 and February
2014. Extraction of genomic DNA was performed for 65 concentrated cysts and 2
cultured trophozoites. Partial sequences of tpi including 148-bp and 81-bp were
amplified for detection the genotypes A and B using RFLP- PCR protocol
respectively. RESULTS: PCR results showed that out of 67 patients with giardiasis
infection, genotype A (148 bp) was detected in 40 isolates (59.70%) compared to
genotype B (81 bp) isolated was detected in 25 isolates (37.31%). Also two
isolates (2.98%) had mix infection infected with genotype A and B. By comparing
the frequency of genotype A (81.8%) and genotype B (13.6%), we found that
genotype A is six times higher prevalence than genotype B in patients with
diarrhea. CONCLUSION: We suggest that using sensitive techniques and larger
sample for detection of G. lamblia genotypes and their subtypes would be
necessary for investigation the immune system respond and correlation with
diarrhea in the future studies in Iran.
PMID- 25120897
TI - Discrimination of Entamoeba Spp. in children with dysentery.
AB - AIM: The present study was performed in order to differentiate E. histolytica and
E. dispar in children from Gorgan city, using a PCR method. BACKGROUND:
Differential detection of two morphologically indistinguishable protozoan
parasites Entamoeba histolytica and E. dispar has a great clinical and
epidemiological importance because of potential invasive pathogenic E.
histolytica and non-invasive parasite E. dispar. PATIENTS AND METHODS: One
hundred and five dysentery samples were collected from children hospitalized in
Taleghani hospital in Gorgan city. The fecal specimens were examined by light
microscopy (10X then 40X) to distinguish Entamoeba complex. A single round PCR
amplifying partial small-subunit rRNA gene was performed on positive microscopy
samples to differentiate E. histolytica/ E. dispar and E. moshkovskii from each
other. RESULTS: Twenty-five specimens (23.8%) were positive for Enramoeba complex
in direct microscopic examination. PCR using positive controls indicated E.
histolytica and E. dispar in two (2/25, 8%) and three (3/25, 12%) samples,
respectively. CONCLUSION: There is a warrant to performing molecular diagnosis
for stool examination at least in hospitalized children in order to prevent
incorrect reports from laboratories and consequently mistreating by physicians.
PMID- 25120899
TI - Cannabinoid hyperemesis should be recognised as an effect of chronic cannabis
abuse.
AB - Here we describe the second reported case of cannabinoid hyperemesis in UK. A 42
years old patient presented on more than one occasion with vomiting, abdominal
pain, fever and dehydration and treated as sepsis with antibiotics. Extensive
investigations including upper GI endoscopy, colonoscopy, chest X-ray, abdominal
ultrasound, abdominal CT scan, barium swallow and echocardiogram; all reported
normal. Once the diagnosis of cannabinoid hyperemesis was established, he was
advised to abstain from cannabis use resulting in complete resolution of his
symptoms.
PMID- 25120900
TI - Right cervical lymphadenopathy: a rare presentation of metastatic hepatocellular
carcinoma.
AB - Hepatocellular carcinoma (HCC) is the most common, malignant tumor of the liver.
Hepatocellular carcinoma (HCC) commonly metastasizes to the lungs, abdominal
lymph nodes, adrenal glands, or bones. Distant lymph node metastases are rare in
hepatocellular carcinoma. A 49-year-old male patient presented with right sided
neck mass. On examination there was right cervical lymphadenopathy and
hepatomegaly. Excisional cervical lymph node biopsy showed metastatic carcinoma.
However, further examination of the biopsy specimen for immuno-histochemistry
markers, shows positivity for HepPar-1 & CD-10 suggestive of hepatocellular
carcinoma. Considering the high incidence of HCC in Asia, a special attention
should be given to such unusual site of presentation and metastasis of HCC;
therefore, not to miss the diagnosis.
PMID- 25120901
TI - An unusual cause of upper gastrointestinal bleeding.
PMID- 25120902
TI - Recent advances in oesophageal diseases.
AB - Dong Y, Qi B, Feng XY, Jiang CM. Meta-analysis of Barrett's esophagus in China.
World J Gastroenterol 2013;19(46):8770-8779 The disease pattern of Barrett's
esophagus (BE) in China is poorly characterised particularly in comparison with
other developed countries. This meta-analysis of 3873 cases of BE collated from
69 clinical studies conducted in 25 provinces between 2000 and 2011 investigated
the epidemiology and characteristics of BE in China compared to Western
countries. The total endoscopic detection rate of BE was 1.0% (95%CI: 0.1%-1.8%)
with an average patient age of 49.07 +/- 5.09 years, lower than many Western
countries.The authors postulate this may be attributed to environmental risk
factor variation, distinct genetics and different medical practice including
diagnostic criteria for BE and expertise in endoscopy. This study identified a
1.781 male predominancefor BE in China, consistent with Western reports. Short
segment BE accounted for 80.3% of cases with island type and cardiac type the
most common endoscopic (44.8%) and histological (40.0%) manifestations
respectively. Of the 1283 BE cases followed up for three to 36 months the
incidence of esophageal cancer was 1.418 per 1000 person-years, lower than the
incidence reported in Western countries. Lee HS, Jeon SW. Barrett esophagus in
Asia: same disease with different pattern. ClinEndosc 2014;47(1):15-22 Barrett's
esophagus (BE) is a common, pre-cancerous condition characterised by intestinal
metaplasia of squamous esophageal epithelium usually attributed to chronic
gastric acid exposure. This review article explores important differences in the
disease pattern of BE between Asian and the Western countries. Overall the
prevalence of BE is lower in Asia compared to the West with a greater proportion
of short-segment type. The authors identify great variability in the endoscopic
and pathologic diagnostic criteria for BE. Many of the studies in Asian countries
did not use a standardised four-quadrant biopsy protocol which may have led to an
underestimation of BE prevalence. The review highlights an increasing incidence
of esophageal adenocarcinoma in the West but unclear disease trend in Asia with
inter-country variability. Similarly in Asian and Western countries BE is
associated with the presence of hiatus hernia, advancing age, male gender,
alcohol consumption, smoking, abdominal obesity and longer duration of gastro
esophageal reflux disease. The authors postulate that Helicobacter pylori
infection, more prevalent in Asia than the West, may have a protective effect on
BE. There is a need for larger, prospective studies to further clarify the
disease pattern of BE in Asian countries. Clearly standardisation of the
diagnostic process for BE is important to validate the differences in disease
trends between Asian and Western countries. Kiadaliri AA. Gender and social
disparities in esophagus cancer incidence in Iran, 2003-2009: a time trend
province-level study.Asian Pac J Cancer Prev 2014;15(2):623-7 Esophageal cancer
(EC) is a major cause of morbidity and mortality particuarly in Iran where the
incidence rate exceeds the global average. An understanding of the factors
influencing the province-specific incidence of EC in Iran is important to inform
disease-prevention strategies and address health inequalities. This ecological
study used cancer registry data to investigate the relationship between gender
and social class and the incidence of EC in Iran at province-level between 2003
and 2009. The age standardised incidence rates (ASIR) of EC were greatest in the
Northern provinces of Iran, specifically Razavi Khorasan in males and Kordestan
in females. Overall the EC incidence did not significantly differ according to
gender. Interestingly, during the study period the ASIR increased by 4.6% per
year in females (p=0.08) and 6.5% per year in males (p=0.02). This may reflect
increasing rates of establised risk factors for EC including obsesity and gastro
esophageal reflux disease alongside more vigilant recording of new cases. Social
class was inversely associated with the ASIR of EC regardless of gender which may
be attributed to class differences in risk factor distribution particularly
smoking, diet and obesity. An appreciation for the limitations of an
epidemiological study is important when interpreting results which should be
further evaluated in future studies. Islami F et al.Determinants of
gastroesophageal reflux disease, including hookah smoking and opium use- A cross
sectional analysis of 50,000 individuals. PLoS One 2014;9(2):e89256
Gastroesophageal reflux disease (GERD) is a highly prevalent cause of
gastrointestinal symptoms worldwide incurring great cost to the primary and
secondary healthcare sectors. An improved understanding of the factors which
influence GERD symptoms in low- to medium- income countries may inform public
health initiatives. This study analysed prospective data from the Golestan cohort
study, primarily established to investigate determinants of upper
gastrointestinal cancers, toexplore the risk factors influencing GERD symptoms
(regurgitation and/or heartburn) in 50,045 individuals aged 40-75 years in
Golestan Province, Iran enrolled between 01/2004 and 06/2008.Of note, 39.12% of
individuals denied ever experiencing GERD symptoms. A further 19.89% reported at
least once weekly GERD symptoms with 11.83% experiencing daily symptoms. Severe
symptoms, defined as disturbing daily work or sleep, were recorded by 11.33% of
individuals. Separately the occurrence of daily GERD symptoms and severe symptoms
were inversely associated with male gender (OR 0.36, 95% CI 0.33-0.39 both),
level of formal education (p=0.01 and p=0.001 respectively), wealth score
(p<0.001 both) and regular nass chewing (OR 0.86, 95% CI 0.75-0.98 and OR 0.87,
95% CI 0.76-0.99 respectively)and were positively associated with body mass index
(p<0.001 both), intensity of physical activity (p=0.04 both), cigarette pack
years (p<0.001 both), alcohol consumption (OR 1.36, 95% CI 1.13-1.64 and OR 1.53,
95% CI 1.28-1.83 respectively) and opium use (OR 1.82, 95% CI 1.67-1.99 and OR
1.70, 95% CI 1.55-1.87 respectively).In addition hookah smoking had a borderline
significant correlation with mild and moderate severity GERD symptoms in
individuals who had never smoked cigarettes (OR 1.41, 95% CI 1.00-1.99 and OR
1.25, 95% CI 0.99-1.57 respectively). Overall this large study contributes useful
data to inform the prevention and management of GERD symptoms particularly
regarding the use of hookah, opium and nass which was previously unclear. Barbera
M et al. The human squamous oesophagus has widespread capacity for clonal
expansion from cells at diverse stages of differentiation. Gut 2014;0:1-9.
doi:10.1136/gutjnl-2013-306171 Current knowledge on human esophageal tissue
homeostasis and injury repair is derived predominantly from murine models and
hence may be inaccurate due to cellular and architectural differences. This study
used 3D imaging in conjunction withstaining for cell lineage markers to
investigate the cellular mechanisms involved in homeostasis of the normal human
squamous esophagus in 10 participants undergoing esophagectomy for esophageal
cancer. The self-renewal potential of cell subpopulations was also assessed using
in vitro and in vivo assays. A decreasing gradient of cell proliferation was
observed from the inter-papillary basal layer to the tip of the papilla where
there was no evidence of mitosis. The expression ofbeta1-integrin, a putative
stem cell marker, was consistent throughout the basal layer and therefore the
entire basal layer can be considered undifferentiated. Quiescent beta1
integrin/CD34-positive cells which failed to stain for CD45, S-100 or F4-80were
identified at the tip of the papilla suggesting this is an extension of the basal
layer. Contrary to previous data, this study found progenitor cells widely
distributed in human esophageal tissue and included already differentiated
epithelial cells. This insight into esophageal homeostasis may inform future
studies exploring the pathological mechanisms underpinning homeostatic disruption
in disease states such as Barrett's esophagus. Papers were prepared by: Drs
Ishfaq Ahmad and Luke Materacki, Department of Medicine, Alexandra Hospital,
Redditch, UK.
PMID- 25110579
TI - Ten things to get right for marine conservation planning in the Coral Triangle.
AB - Systematic conservation planning increasingly underpins the conservation and
management of marine and coastal ecosystems worldwide. Amongst other benefits,
conservation planning provides transparency in decision-making, efficiency in the
use of limited resources, the ability to minimise conflict between diverse
objectives, and to guide strategic expansion of local actions to maximise their
cumulative impact. The Coral Triangle has long been recognised as a global marine
conservation priority, and has been the subject of huge investment in
conservation during the last five years through the Coral Triangle Initiative on
Coral Reefs, Fisheries and Food Security. Yet conservation planning has had
relatively little influence in this region. To explore why this is the case, we
identify and discuss 10 challenges that must be resolved if conservation planning
is to effectively inform management actions in the Coral Triangle. These are:
making conservation planning accessible; integrating with other planning
processes; building local capacity for conservation planning; institutionalising
conservation planning within governments; integrating plans across governance
levels; planning across governance boundaries; planning for multiple tools and
objectives; understanding limitations of data; developing better measures of
progress and effectiveness; and making a long term commitment. Most important is
a conceptual shift from conservation planning undertaken as a project, to
planning undertaken as a process, with dedicated financial and human resources
committed to long-term engagement.
PMID- 25120905
TI - Analysis of beta-N-methylamino-L-alanine (BMAA) in spirulina-containing
supplements by liquid chromatography-tandem mass spectrometry.
AB - Over the last decade the amino acid beta-N-methylamino-L-alanine (BMAA) has come
under intense scrutiny. International laboratory and epidemiological research
continues to support the hypothesis that environmental exposure to BMAA (e.g.,
through dietary practices, water supply) can promote the risk of various
neurodegenerative diseases. A wide variety of cyanobacteria spp. have previously
been reported to produce BMAA, with production levels dependent upon species,
strain and environmental conditions. Since spirulina (Arthrospira spp.) is a
member of the cyanobacteria phylum frequently consumed via dietary supplements,
the presence of BMAA in such products may have public health implications. In the
current work, we have analyzed ten spirulina-containing samples for the presence
of BMAA; six pure spirulina samples from two separate raw materials suppliers,
and four commercially-available multi-ingredient products containing 1.45 g of
spirulina per 8.5 g serving. Because of controversy surrounding the measurement
of BMAA, we have used two complementary liquid chromatography-tandem mass
spectrometry (LC-MS/MS) methods: one based on reversed phase LC (RPLC) with
derivatization and the other based on hydrophilic interaction LC (HILIC).
Potential matrix effects were corrected for by internal standardization using a
stable isotope labeled BMAA standard. BMAA was not detected at low limits of
detection (80 ng/g dry weight) in any of these product samples. Although these
results are reassuring, BMAA analyses should be conducted on a wider sample
selection and, perhaps, as part of ongoing spirulina production quality control
testing and specifications.
PMID- 25120903
TI - Vascular disruption and blood-brain barrier dysfunction in intracerebral
hemorrhage.
AB - This article reviews current knowledge of the mechanisms underlying the initial
hemorrhage and secondary blood-brain barrier (BBB) dysfunction in primary
spontaneous intracerebral hemorrhage (ICH) in adults. Multiple etiologies are
associated with ICH, for example, hypertension, Alzheimer's disease, vascular
malformations and coagulopathies (genetic or drug-induced). After the initial
bleed, there can be continued bleeding over the first 24 hours, so-called
hematoma expansion, which is associated with adverse outcomes. A number of
clinical trials are focused on trying to limit such expansion. Significant
progress has been made on the causes of BBB dysfunction after ICH at the
molecular and cell signaling level. Blood components (e.g. thrombin, hemoglobin,
iron) and the inflammatory response to those components play a large role in ICH
induced BBB dysfunction. There are current clinical trials of minimally invasive
hematoma removal and iron chelation which may limit such dysfunction.
Understanding the mechanisms underlying the initial hemorrhage and secondary BBB
dysfunction in ICH is vital for developing methods to prevent and treat this
devastating form of stroke.
PMID- 25120908
TI - What can FGF23 do without Klotho?
PMID- 25120907
TI - Quantitative phenotyping of bone fracture repair: a review.
AB - Fracture repair is a complex process that involves the interaction of numerous
molecular factors, cell lineages and tissue types. These biological processes
allow for an impressive feat of engineering: an elastic soft callus is
progressively replaced by a more rigid and mineralized callus. During this
reparative phase, the healing bone is exposed to a risk of re-fracture. Bone
volume and bone quality are the two major factors determining the strength of the
callus. Although both factors are important, often only bone volume is analyzed
and reported in preclinical studies. Recent developments in techniques for
examining bone quality in the callus will enable the rapid and detailed analysis
of its material properties and its microstructure. This review aims to give an
overview of the methods available for quantitatively phenotyping the bone callus
in preclinical studies such as Raman spectroscopy, nanoindentation, scanning
acoustic microscopy, in vivo micro-computed tomography (micro-CT) and high
resolution micro-CT. Consolidated and emerging experimental methods are described
with a focus on their applicability, and with examples of their utilization.
PMID- 25120909
TI - Instructions for producing a mouse model of glucocorticoid-induced osteoporosis.
AB - Glucocorticoids are effective drugs used for the treatment of inflammatory
diseases such as rheumatoid arthritis or asthma. Furthermore, they regulate
various physiological processes, including bone remodeling. However, long-term
high- and even low-dose glucocorticoid use is associated with a compromised bone
quality and an increased fracture risk. At the cellular level, glucocorticoids
suppress bone formation and stimulate bone resorption, which leads to loss of
bone mass. To investigate the underlying mechanisms and new therapeutic
strategies, the in vivo model for glucocorticoid-induced bone loss is widely
used. This protocol outlines the common procedure that is currently used for the
induction of bone loss in mice using glucocorticoids. It further provides useful
hints and highlights possible pitfalls to take into account before starting an
experiment.
PMID- 25120906
TI - MicroRNAs as regulators of bone homeostasis and bone metastasis.
AB - MicroRNAs (miRNAs) are short, endogenous RNAs that have essential roles in
regulating gene expression through the disruption of target genes. The miRNA
induced suppression can occur through Argonaute-mediated cleavage of target mRNAs
or by translational inhibition. System-wide studies have underscored the integral
role that miRNAs play in regulating the expression of essential genes within bone
marrow stromal cells. The miRNA expression has been shown to enhance or inhibit
cell differentiation and activity, and elucidating miRNA targets within bone
marrow cells has revealed novel regulations during normal bone development.
Importantly, multiple studies have shown that miRNA misexpression mediates the
progression of bone-related pathologies, including osteopetrosis and
osteoporosis, as well as the development and progression of osteosarcoma.
Furthermore, recent studies have detailed the capacity for miRNAs to influence
bone metastasis from a number of primary carcinomas. Taken together, these
findings reveal the significant clinical potential for miRNAs to regulate bone
homeostasis, as well as to mediate bone-related pathologies.
PMID- 25120910
TI - Enhanced osteoblastogenesis in three-dimensional collagen gels.
AB - Growth and differentiation of osteoblasts are often studied in cell cultures. In
vivo, however, osteoblasts are embedded within a complex three-dimensional (3D)
microenvironment, which bears little relation to standard culture flasks. Our
study characterizes osteoblast-like cells cultured in 3D collagen gels and
compares them with cells in two-dimensional (2D) cultures. Primary rat
osteoblasts and MC3T3-E1 cells were seeded within type I collagen gels, and
differentiation was determined by mineral staining and gene expression analysis.
Cells growing in 3D gels showed positive mineral staining and induction of
osteoblast marker genes earlier than cells growing in 2D. A number of genes,
including osteocalcin, bone sialoprotein, alkaline phosphatase and dentin matrix
protein 1, were already highly upregulated in 3D cultures 24 h after seeding. The
early expression of osteoblast genes was dependent on the 3D structure and was
not induced in cells growing on collagen-coated dishes in 2D. Comparison of
thymidine incorporation between cells in 3D and 2D cultures treated with agents
that induce proliferation-transforming growth factor beta, platelet-derived
growth factor and lactoferrin-showed a much greater response in 3D gels. Cells in
3D cultures were also much more sensitive to inhibition of proliferation by the
protein kinase inhibitor imatinib mesylate. The 3D collagen gels better represent
the physiological bone environment and offer a number of technical advantages for
the study of osteoblasts in vitro. These studies have additional practical
implications as 3D collagen gels are considered as a scaffold material in
regenerative medicine for the repair of bone defects.
PMID- 25120913
TI - Need of surveillance response systems to combat Ebola outbreaks and other
emerging infectious diseases in African countries.
AB - There is growing concern in Sub-Saharan Africa about the spread of the Ebola
virus disease (EVD), formerly known as Ebola haemorrhagic fever, and the public
health burden that it ensues. Since 1976, there have been 885,343 suspected and
laboratory confirmed cases of EVD and the disease has claimed 2,512 cases and 932
fatality in West Africa. There are certain requirements that must be met when
responding to EVD outbreaks and this process could incur certain challenges. For
the purposes of this paper, five have been identified: (i) the deficiency in the
development and implementation of surveillance response systems against Ebola and
others infectious disease outbreaks in Africa; (ii) the lack of education and
knowledge resulting in an EVD outbreak triggering panic, anxiety, psychosocial
trauma, isolation and dignity impounding, stigmatisation, community ostracism and
resistance to associated socio-ecological and public health consequences; (iii)
limited financial resources, human technical capacity and weak community and
national health system operational plans for prevention and control responses,
practices and management; (iv) inadequate leadership and coordination; and (v)
the lack of development of new strategies, tools and approaches, such as improved
diagnostics and novel therapies including vaccines which can assist in
preventing, controlling and containing Ebola outbreaks as well as the spread of
the disease. Hence, there is an urgent need to develop and implement an active
early warning alert and surveillance response system for outbreak response and
control of emerging infectious diseases. Understanding the unending risks of
transmission dynamics and resurgence is essential in implementing rapid effective
response interventions tailored to specific local settings and contexts.
THEREFORE, THE FOLLOWING ACTIONS ARE RECOMMENDED: (i) national and regional inter
sectorial and trans-disciplinary surveillance response systems that include early
warnings, as well as critical human resources development, must be quickly
adopted by allied ministries and organisations in African countries in epidemic
and pandemic responses; (ii) harnessing all stakeholders commitment and advocacy
in sustained funding, collaboration, communication and networking including
community participation to enhance a coordinated responses, as well as tracking
and prompt case management to combat challenges; (iii) more research and
development in new drug discovery and vaccines; and (iv) understanding the
involvement of global health to promote the establishment of public health
surveillance response systems with functions of early warning, as well as
monitoring and evaluation in upholding research-action programmes and innovative
interventions.
PMID- 25120911
TI - The reversal phase of the bone-remodeling cycle: cellular prerequisites for
coupling resorption and formation.
AB - The reversal phase couples bone resorption to bone formation by generating an
osteogenic environment at remodeling sites. The coupling mechanism remains poorly
understood, despite the identification of a number of 'coupling' osteogenic
molecules. A possible reason is the poor attention for the cells leading to
osteogenesis during the reversal phase. This review aims at creating awareness of
these cells and their activities in adult cancellous bone. It relates cell events
(i) on the bone surface, (ii) in the mesenchymal envelope surrounding the bone
marrow and appearing as a canopy above remodeling surfaces and (iii) in the bone
marrow itself within a 50-MUm distance of this canopy. When bone remodeling is
initiated, osteoprogenitors at these three different levels are activated, likely
as a result of a rearrangement of cell-cell and cell-matrix interactions.
Notably, canopies are brought under the osteogenic influence of capillaries and
osteoclasts, whereas bone surface cells become exposed to the eroded matrix and
other osteoclast products. In several diverse pathophysiological situations,
including osteoporosis, a decreased availability of osteoprogenitors from these
local reservoirs coincides with decreased osteoblast recruitment and impaired
initiation of bone formation, that is, uncoupling. Overall, this review stresses
that coupling does not only depend on molecules able to activate osteogenesis,
but that it also demands the presence of osteoprogenitors and ordered cell
rearrangements at the remodeling site. It points to protection of local
osteoprogenitors as a critical strategy to prevent bone loss.
PMID- 25120914
TI - Changes in sex difference in swimming speed in finalists at FINA World
Championships and the Olympic Games from 1992 to 2013.
AB - BACKGROUND: This study investigated swimming speeds and sex differences of
finalists competing at the Olympic Games (i.e. 624 female and 672 male athletes)
and FINA World Championships (i.e. 990 women and 1008 men) between 1992 and 2013.
METHODS: Linear, non-linear and multi-level regression models were used to
investigate changes in swimming speeds and sex differences for champions and
finalists. RESULTS: Regarding finalists in FINA World Championships and Olympic
Games, swimming speed increased linearly in both women and men in all disciplines
and race distances. Male world champions' swimming speed remained stable in 200 m
butterfly, 400 m, 800 m and 1,500 m freestyle. Considering women, swimming speed
remained unchanged in 50 m and 400 m freestyle. In the Olympic Games, swimming
speed of male champions remained unchanged in 200 m breaststroke, 50 m, 400 m,
800 m and 1,500 m freestyle. Female Olympic champions' swimming speed remained
stable in 100 m and 200 m backstroke, 100 m butterfly, 200 m individual medley,
50 m and 200 m freestyle. Evaluating sex differences between finalists in FINA
World Championships, results showed a linear decrease in 100 m breaststroke and
200 m butterfly and a non-linear increase in 100 m backstroke. In finals at the
Olympic Games, the sex difference decreased linearly for 100 m backstroke, 400 m
and 800 m freestyle. However, a linear increase for 200 m butterfly can be
reported. Considering Olympic and world champions, the sex difference remained
stable in all disciplines and race distances. CONCLUSION: Swimming speed of the
finalists at the Olympic Games and FINA World Championships increased linearly.
The top annual female swimmers increased swimming speed rather at longer race
distances (i.e. 800 m and 1,500 m freestyle, 200 m butterfly, and 400 m
individual medley), whereas the top annual male swimmers increased it rather at
shorter race distances (i.e. 100 m and 200 m freestyle, 100 m butterfly, and 100
m breaststroke). Sex difference in swimming was unchanged in Olympic and world
champions. Finalists and champions at the Olympic Games and FINA World
Championships reduced the sex difference with increasing race distance.
PMID- 25120915
TI - Relationship between age and elite marathon race time in world single age records
from 5 to 93 years.
AB - BACKGROUND: The aims of the study were (i) to investigate the relationship
between elite marathon race times and age in 1-year intervals by using the world
single age records in marathon running from 5 to 93 years and (ii) to evaluate
the sex difference in elite marathon running performance with advancing age.
METHODS: World single age records in marathon running in 1-year intervals for
women and men were analysed regarding changes across age for both men and women
using linear and non-linear regression analyses for each age for women and men.
RESULTS: The relationship between elite marathon race time and age was non-linear
(i.e. polynomial regression 4(th) degree) for women and men. The curve was U
shaped where performance improved from 5 to ~20 years. From 5 years to ~15 years,
boys and girls performed very similar. Between ~20 and ~35 years, performance was
quite linear, but started to decrease at the age of ~35 years in a curvilinear
manner with increasing age in both women and men. The sex difference increased
non-linearly (i.e. polynomial regression 7(th) degree) from 5 to ~20 years,
remained unchanged at ~20 min from ~20 to ~50 years and increased thereafter. The
sex difference was lowest (7.5%, 10.5 min) at the age of 49 years. CONCLUSION:
Elite marathon race times improved from 5 to ~20 years, remained linear between
~20 and ~35 years, and started to increase at the age of ~35 years in a
curvilinear manner with increasing age in both women and men. The sex difference
in elite marathon race time increased non-linearly and was lowest at the age of
~49 years.
PMID- 25120916
TI - Cervical isometric strength and range of motion of elite rugby union players: a
cohort study.
AB - BACKGROUND: Head and neck injury is relatively common in Rugby Union. Despite
this, strength and range-of-motion characteristics of the cervical spine are
poorly characterised. The aim of this study was to provide data on the strength
and range-of-motion of the cervical spine of professional rugby players to guide
clinical rehabilitation. METHODS: A cohort study was performed evaluating 27
players from a single UK professional rugby club. Cervical isometric strength and
range-of-motion were assessed in 3 planes of reference. Anthropometric data was
collected and multivariate regression modelling performed with a view to
predicting cervical isometric strength. RESULTS: Largest forces were generated in
extension, with broadly equal isometric side flexion forces at around 90% of
extension values. The forwards generated significantly more force than the
backline in all parameters bar flexion. The forwards had substantially reduced
cervical range-of-motion and larger body mass, with differences observed in
height, weight, neck circumference and chest circumference (p < 0.002). Neck
circumference was the sole predictor of isometric extension (adjusted R(2) =
30.34). CONCLUSION: Rehabilitative training programs aim to restore individuals
to pre-injury status. This work provides reference ranges for the strength and
range of motion of the cervical spine of current elite level rugby players.
PMID- 25120917
TI - Reforming Cardiovascular Care in the United States towards High-Quality Care at
Lower Cost with Examples from Model Programs in the State of Michigan.
AB - Despite its status as a world leader in treatment innovation and medical
education, a quality chasm exists in American health care. Care fragmentation and
poor coordination contribute to expensive care with highly variable quality in
the United States. The rising costs of health care since 1990 have had a huge
impact on individuals, families, businesses, the federal and state governments,
and the national budget deficit. The passage of the Affordable Care Act
represents a large shift in how health care is financed and delivered in the
United States. The objective of this review is to describe some of the economic
and social forces driving health care reform, provide an overview of the Patient
Protection and Affordable Care Act (ACA), and review model cardiovascular quality
improvement programs underway in the state of Michigan. As health care
reorganization occurs at the federal level, local and regional efforts can serve
as models to accelerate improvement toward achieving better population health and
better care at lower cost. Model programs in Michigan have achieved this goal in
cardiovascular care through the systematic application of evidence-based care,
the utilization of regional quality improvement collaboratives, community-based
childhood wellness promotion, and medical device-based competitive bidding
strategies. These efforts are examples of the direction cardiovascular care
delivery will need to move in this era of the Affordable Care Act.
PMID- 25120918
TI - A new paradigm is needed for medical education in the mid-twenty-first century
and beyond: are we ready?
AB - The twentieth century witnessed profound changes in medical education. All these
changes, however, took place within the existing framework, suggested by Flexner
a century ago. The present paper suggests that we are approaching a singularity
point, where we shall have to change the paradigm and be prepared for an entirely
new genre of medical education. This suggestion is based upon analysis of
existing and envisaged trends: first, in technology, such as availability of
information and sophisticated simulations; second, in medical practice, such as
far-reaching interventions in life and death that create an array of new moral
dilemmas, as well as a change in patient mix in hospitals and a growing need of
team work; third, in the societal attitude toward higher education. The structure
of the future medical school is delineated in a rough sketch, and so are the
roles of the future medical teacher. It is concluded that we are presently not
prepared for the approaching changes, neither from practical nor from attitudinal
points of view, and that it is now high time for both awareness of and
preparation for these changes.
PMID- 25120920
TI - Delivering bad news: an approach according to jewish scriptures.
AB - Despite a preoccupation in the medical literature with developing an effective
approach for breaking bad news, the sources are based on personal opinion alone
and only in some instances on qualitative research. Recognizing the gravity of
this topic coupled with respect for the wisdom of the written and oral Jewish
scriptures, this work is an attempt to delve into the diverse ancient writings to
draw conclusions regarding a recommended methodology to guide and inform this
task. It is interesting to learn that most elements related to this topic have
previously been raised in various forms in the scriptures. The issues range from
where, when, and how the bearer of bad news should undertake this duty, to
details such as the environment, the format, the speed, and depth of the details
to be disclosed. The essence of this paper is to enrich the reader using both
positive and negative examples found in the Jewish heritage. Adopting these
principles will hopefully provide an effective method for performing this
unpleasant obligation, with the goal of limiting harmful consequences as much as
possible.
PMID- 25120919
TI - The perils of complementary alternative medicine.
AB - More than 11,000 articles lauding alternative medicine appear in the PubMed
database, but there are only a few articles describing the complications of such
care. Two patients suffering from complications of alternative medicine were
treated in our hospital: one patient developed necrotizing fasciitis after
acupuncture, and the second developed an epidural hematoma after chiropractic
manipulation. These complications serve as a clarion call to the Israeli Health
Ministry, as well as to health ministries around the world, to include
complementary medicine under its inspection and legislative authority.
PMID- 25120921
TI - Spermatocytic variant of classic seminoma: a report of five cases and a brief
review of the literature.
AB - BACKGROUND: Spermatocytic seminoma is a rare testicular malignancy, appearing in
the adult population. It has a good prognosis and a low rate of metastatic
potential. OBJECTIVES: We present five cases diagnosed and treated with
radiotherapy at Rambam Health Care Campus in Haifa, Israel. METHODS: Between 1974
and 1996, five patients with stage I spermatocytic seminoma were referred post
orchiectomy to the Northern Israel Oncology Center. All five patients presented
with the typical pathological features of the spermatocytic variant of classic
seminoma, and all were staged clinically and radiologically. RESULTS: Mean age at
diagnosis was 44 years (range 30-58 years). Main symptoms included a palpable
testicular mass and/or testicular enlargement. Mean duration of symptoms was 9
months (range 0.5-24 months). Three patients were irradiated to the para
aortic/ipsilateral iliacal lymph nodes (mean total dose 2,500 cGy), one patient
with 4,000 cGy. One patient was irradiated to the bilateral iliacal lymph nodes
(2,600 cGy). With a median follow-up of 15 years, four patients are alive with no
evidence of disease or severe late side effects. One patient developed severe
lymphedema and symptomatic peripheral vascular disease, stage IIA prostate
carcinoma (hormonal and brachytherapy treatment) and a non-secretory hypophyseal
adenoma (surgically removed); he died at the age of 75 due to severe peripheral
vascular and coronary heart disease with no evidence of his first or second
primaries. CONCLUSIONS: Prognosis is excellent and does not differ from classic
seminoma. As in the accumulated experience in early-stage, low-risk classic
seminoma, we suggest surveillance as the preferred policy.
PMID- 25120922
TI - Vulvar cancer in the north of Israel.
AB - PURPOSE: This is a population study of patients who were treated for vulvar
cancer in a tertiary center in northern Israel, aimed to report clinical
findings, treatment, and outcome. METHODS: A retrospective chart review of all
medical records of consecutive patients who were treated for vulvar cancer in the
years 1993-2012 was conducted. Data extracted from the medical records included
demographics, histology, size of lesion, stage of disease at diagnosis, type of
treatment, radiation dose, follow-up, recurrence, and survival. RESULTS: The
study included 44 patients with a median age of 69.8 years (range, 42-93 years).
Thirty-five (79.5%) of the patients were of Jewish descent, five were Arabic, and
four were of other descent. The most common histology type was squamous cell
carcinoma in 35 (79.5%) patients. Most patients were staged FIGO II-III at time
of diagnosis. Surgery was the most common primary treatment modality (54.2%).
Twenty-three (52.2%) patients had recurrent disease. Older age and more advanced
stage at diagnosis were associated with increased mortality. CONCLUSION: Vulvar
cancer is common among elderly women with co-morbidities who present in advanced
disease stage; all these factors are significant for survival.
PMID- 25120923
TI - Hitler's Jewish Physicians.
AB - The mystery behind the behavior of infamous personalities leaves many open
questions, particularly when related to the practice of medicine. This paper
takes a brief look at two Jewish physicians who played memorable roles in the
life of Adolf Hitler.
PMID- 25120925
TI - Interaction of ingested leucine with glycine on insulin and glucose
concentrations.
AB - The majority of individual amino acids increase insulin and attenuate the plasma
glucose response when ingested with glucose. Objective. To determine whether
ingestion of two amino acids simultaneously, with glucose, would result in an
additive effect. Leucine (Leu) and glycine (Gly) were chosen because they were
two of the most potent glucose-lowering amino acids when given individually.
Materials and Methods. Nine subjects received test items on four separate days.
The first was a water control, then 25 g glucose, or Leu + Gly (1 mmol/kg fat
free mass each) +/-25 g glucose, in random order. Glucose, insulin, and glucagon
were measured frequently for 2.5 hours. Net areas were calculated. Results. The
glucose area response decreased by 66%. The insulin area response increased by
24% after ingestion of Leu + Gly + glucose compared to ingestion of glucose
alone. The decrease in glucose response was not additive; the increase in insulin
response was far less than additive when compared to previously published
individual amino acid results. The glucagon concentration remained unchanged.
Conclusion. There is an interaction between Leu and Gly that results in a
markedly attenuated glucose response. This occurred with a very modest increase
in insulin response. Changes in glucagon response could not explain the results.
The mechanism is unknown.
PMID- 25120924
TI - A Clinical and Confocal Microscopic Comparison of Transepithelial PRK and LASEK
for Myopia.
AB - Purpose. To compare the clinical and confocal microscopic results of
transepithelial PRK versus LASEK for correction of myopia. Materials and Methods.
Twelve patients with myopia received transepithelial PRK in one eye and LASEK in
the other. In transepithelial PRK-treated eyes, the corneal epithelium was
removed with 40 microns of excimer laser ablation and in LASEK-treated eyes with
25-second application of 18% ethanol. Time to epithelial healing, ocular
discomfort, uncorrected and best corrected visual acuities, manifest refraction,
haze, greyscale value, and keratocyte apoptosis in confocal microscopy were
recorded. Results. The mean time to epithelial healing was significantly longer
after LASEK (4.00 +/- 0.43 versus 3.17 +/- 0.6 days). On day 1, ocular discomfort
was significantly higher after transepithelial PRK. The grade of haze, keratocyte
apoptosis, and greyscale value in confocal microscopy were significantly higher
in transepithelial PRK-treated eyes at 1 month. All transepithelial PRK- and
LASEK-treated eyes achieved 20/25 or better UCVA and were within +/-1.00 D of
emmetropia at final visits. Conclusions. Both transepithelial PRK and LASEK offer
effective correction of myopia at 1 year. However, LASEK appeared to induce less
discomfort and less intense wound healing in the early postoperative period.
PMID- 25120926
TI - Sequential Statistical Optimization of Media Components for the Production of
Glucoamylase by Thermophilic Fungus Humicola grisea MTCC 352.
AB - Glucoamylase is an industrially important enzyme which converts soluble starch
into glucose. The media components for the production of glucoamylase from
thermophilic fungus Humicola grisea MTCC 352 have been optimized. Eight media
components, namely, soluble starch, yeast extract, KH2PO4, K2HPO4, NaCl, CaCl2,
MgSO4 .7H2O, and Vogel's trace elements solution, were first screened for their
effect on the production of glucoamylase and only four components (soluble
starch, yeast extract, K2HPO4, and MgSO4 .7H2O) were identified as statistically
significant using Plackett-Burman design. It was fitted into a first-order model
(R (2) = 0.9859). Steepest ascent method was performed to identify the location
of optimum. Central composite design was employed to determine the optimum values
(soluble starch: 28.41 g/L, yeast extract: 9.61 g/L, K2HPO4: 2.42 g/L, and MgSO4
.7H2O: 1.91 g/L). The experimental activity of 12.27 U/mL obtained was close to
the predicted activity of 12.15. High R (2) value (0.9397), low PRESS value
(9.47), and AARD values (2.07%) indicate the accuracy of the proposed model. The
glucoamylase production was found to increase from 4.57 U/mL to 12.27 U/mL, a
2.68-fold enhancement, as compared to the unoptimized medium.
PMID- 25120927
TI - Applying Theory to Understand and Modify Nurse Intention to Adhere to
Recommendations regarding the Use of Filter Needles: An Intervention Mapping
Approach.
AB - The manipulation of glass ampoules involves risk of particle contamination of
parenteral medication, and the use of filter needles has often been recommended
in order to reduce the number of particles in these solutions. This study aims to
develop a theory-based intervention to increase nurse intention to use filter
needles according to clinical guideline recommendations produced by a large
university medical centre in Quebec (Canada). Using the Intervention Mapping
framework, we first identified the psychosocial determinants of nurse intention
to use filter needles according to these recommendations. Second, we developed
and implemented an intervention targeting nurses from five care units in order to
increase their intention to adhere to recommendations on the use of filter
needles. We also assessed nurse satisfaction with the intervention. In total, 270
nurses received the intervention and 169 completed the posttest questionnaire.
The two determinants of intention, that is, attitude and perceived behavioral
control, were significantly higher after the intervention, but only perceived
behavioral control remained a predictor of intention. In general, nurses were
highly satisfied with the intervention. This study provides support for the use
of Intervention Mapping to develop, implement, and evaluate theory-based
interventions in order to improve healthcare professional adherence to clinical
recommendations.
PMID- 25120929
TI - Retracted: Peripheral cytokines as a chemical mediator for postconcussion like
sickness behaviour in trauma and perioperative patients: literature review.
PMID- 25120928
TI - Effects of inactivated Bordetella pertussis on phosphodiesterase in the lung of
ovalbumin sensitized and challenged rats.
AB - This paper indicated that inactivated Bordetella pertussis (iBp) can enhance the
lung airway hyperreactivity of the rats sensitized and challenged with OVA. The
mechanisms were involved in the upregulation of cAMP-PDE activity and PDE4A,
PDE4D, and PDE3 gene expression in the lungs. But only PDE4 activity was
different between the OVA and OVA+iBp groups, and PDE4D expression was
significantly increased in iBp rats alone. So, our data suggested that
cosensitization with OVA and iBp affects lung airway reactivity by modulating the
lung cAMP-PDE activity and PDE4D gene expression.
PMID- 25120930
TI - Performing chest x-rays at inspiration in uncooperative children: the effect of
exercises with a training program for radiology technicians.
AB - Objective. It is difficult to acquire a chest X-ray of a crying infant at maximum
inspiration. A computer program was developed for technician training. Method.
Video clips of 3 babies were used and the moment of deepest inspiration was
determined in the single-frame view. 12 technicians simulated chest radiographs
at normal video speed by pushing a button. The computer program stopped the video
and calculated the period of time to the optimal instant for a chest X-ray.
Demonstration software can be tested at website online. Every technician
simulated 10 chest X-rays for each of the 3 video clips. The technicians then
spent 40 minutes practicing performing chest X-rays at optimal inspiration. The
test was repeated after 5, 20, and 40 minutes of practice. Results. 6
participants showed a significant improvement after exercises (collective 1).
Deviation from the optimal instant for taking an X-ray at inspiration decreased
from 0.39 to 0.22 s after 40 min of practice. 6 technicians showed no significant
improvement (collective 2). Deviation decreased from a low starting value of 0.25
s to 0.21 s. Conclusion. The tested computer program improves the ability of
radiology technicians to take a chest X-ray at optimal inspiration in a crying
child.
PMID- 25120931
TI - The Influence of DNA Extraction Procedure and Primer Set on the Bacterial
Community Analysis by Pyrosequencing of Barcoded 16S rRNA Gene Amplicons.
AB - In this study, the effect of different DNA extraction procedures and primer sets
on pyrosequencing results regarding the composition of bacterial communities in
the ileum of piglets was investigated. Ileal chyme from piglets fed a diet
containing different amounts of zinc oxide was used to evaluate a pyrosequencing
study with barcoded 16S rRNA PCR products. Two DNA extraction methods (bead
beating versus silica gel columns) and two primer sets targeting variable regions
of bacterial 16S rRNA genes (8f-534r versus 968f-1401r) were considered. The SEED
viewer software of the MG-RAST server was used for automated sequence analysis. A
total of 5.2 * 10(5) sequences were used for analysis after processing for read
length (150 bp), minimum sequence occurrence (5), and exclusion of eukaryotic and
unclassified/uncultured sequences. DNA extraction procedures and primer sets
differed significantly in total sequence yield. The distribution of bacterial
order and main bacterial genera was influenced significantly by both parameters.
However, this study has shown that the results of pyrosequencing studies using
barcoded PCR amplicons of bacterial 16S rRNA genes depend on DNA extraction and
primer choice, as well as on the manner of downstream sequence analysis.
PMID- 25120932
TI - Concomitant Colonization of Helicobacter pylori in Dental Plaque and Gastric
Biopsy.
AB - Frequently reported H. pylori antimicrobial therapy failures suggest that there
might be a different niche where the bacteria can stay safe. Current study aims
to examine potential role of oral colonization of H. pylori to feed reinfection
after primary therapy. However, patients who were admitted to the gastroscopy
section were chosen and gastric biopsy and dental plaque specimens were
collected. Molecular and biochemical tests were applied to confirm H. pylori
identity in different colonization niches. Results showed that 88.8% of dyspeptic
patients had epigastric pains with nocturnal awakening when they were hungry (P =
0.023). All patients who received therapy already were again H. pylori positive
while they are still carrying H. pylori in dental plaque (P = 0.001). Moreover,
H. pylori infection was sought in 100% of gastric biopsy's dyspeptic patients who
had ulcerated esophagitis and erosive duodenitis and who were H. pylori positive,
and 75% of dyspeptic patients with duodenum deformity had this bacterium in
gastric biopsies (P = 0.004). Present study showed that only successful
eradication of gastric H. pylori cannot guarantee prevention of reinfection.
Conclusively, a new strategy which indicates concomitant eradication in oral and
gastric colonization can result in clearance of H. pylori infection.
PMID- 25120933
TI - Robotic radical prostatectomy in patients with previous prostate surgery and
radiotherapy.
AB - Herein, we will review the available literature about robot-assisted radical
prostatectomy in patients who have undergone prostate surgery or radiotherapy.
Current data about this topic consists of small case series with limited follow
up. Despite being technically demanding, robot-assisted radical prostatectomy
(RARP) can be considered feasible in either setting. Prostate surgery or
prostatic irradiation should not be considered as a contraindication for robot
assisted radical prostatectomy. Nevertheless, patient counseling about the
possible complications and the need for reintervention is of extreme importance
in this patient population. Early oncologic and functional results of RARP
performed in case of radiorecurrent prostate cancer look promising. Regarding
postprostate surgery RARP, some series have reported comparable results, while
some have demonstrated more inferior outcomes than those of naive cases. In order
to assess the exact functional and oncologic outcome of RARP in patients with
previous prostate surgery and radiotherapy, studies enrolling higher number of
patients and providing longer follow-up data are needed.
PMID- 25120935
TI - Pneumoperitoneum with subcutaneous emphysema after percutaneous endoscopic
gastrostomy.
AB - Percutaneous endoscopic gastrostomy is a safe way for enteral nutrition in
selected patients. Generally, complications of this procedure are very rare but
due to patients general health condition, delayed diagnosis and treatment of
complications can be life threatening. In this study, we present a PEG-related
massive pneumoperitoneum and subcutaneous emphysema in a patient with neuro
Behcet.
PMID- 25120934
TI - Tinnitus-related distress and the personality characteristic resilience.
AB - It has been suggested that personality traits may be prognostic for the severity
of suffering from tinnitus. Resilience as measured with the Wagnild and Young
resilience scale represents a positive personality characteristic that promotes
adaptation to adverse life conditions including chronic health conditions. Aim of
the study was to explore the relation between resilience and tinnitus severity.
In a cross-sectional study with a self-report questionnaire, information on
tinnitus-related distress and subjective tinnitus loudness was recorded together
with the personality characteristic resilience and emotional health, a measure
generated from depression, anxiety, and somatic symptom severity scales. Data
from 4705 individuals with tinnitus indicate that tinnitus-related distress and
to a lesser extent the experienced loudness of the tinnitus show an inverse
correlation with resilience. A mediation analysis revealed that the relationship
between resilience and tinnitus-related distress is mediated by emotional health.
This indirect effect indicates that high resilience is associated with better
emotional health or less depression, anxiety, and somatic symptom severity, which
in turn is associated with a less distressing tinnitus. Validity of resilience as
a predictor for tinnitus-related distress is supported but needs to be explored
further in longitudinal studies including acute tinnitus patients.
PMID- 25120936
TI - Cutaneous Metastases from Primary Hepatobiliary Tumors as the First Sign of Tumor
Recurrence following Liver Transplantation.
AB - Cutaneous metastasis from hepatobiliary tumors is a rare event, especially
following liver transplantation. We report our experience with two cases of
cutaneous metastases from both hepatocellular carcinoma and mixed
hepatocellular/cholangiocarcinoma following liver transplantation, along with a
review of the literature.
PMID- 25120937
TI - A rare cause of testicular metastasis: upper tract urothelial carcinoma.
AB - Metastatic testicular cancers are rare. Primary tumor sources are prostate, lung,
and gastrointestinal tract for metastatic testicular cancers. Metastasis of
urothelial carcinoma (UC) to the testis is extremely rare. Two-thirds of upper
tract urothelial carcinoma (UTUC) is of invasive stage at diagnosis and
metastatic sites are the pelvic lymph nodes, liver, lung, and bone. We report a
rare case of metastatic UTUC to the testis which has not been reported before,
except one case in the literature. Testicular metastasis of UC should be
considered in patients with hematuria and testicular swelling.
PMID- 25120938
TI - Forearm compartment syndrome caused by reperfusion injury.
AB - Compartment syndrome is commonly seen following lower extremity ischemia.
However, upper extremities' compartment syndrome, especially after any vascular
surgical procedures, is infrequent. Herein we report a case of an acute forearm
compartment syndrome that was developed after delayed brachial artery
embolectomy.
PMID- 25120939
TI - Do improvements in balance relate to improvements in long-distance walking
function after stroke?
AB - Stroke survivors identify a reduced capacity to walk farther distances as a
factor limiting their engagement at home and in community. Previous observational
studies have shown that measures of balance ability and balance self-efficacy are
strong predictors of long-distance walking function after stroke. Consequently,
recommendations to target balance during rehabilitation have been put forth. The
purpose of this study was to determine if the changes in balance and long
distance walking function observed following a 12-week poststroke walking
rehabilitation program were related. For thirty-one subjects with hemiparesis
after stroke, this investigation explored the cross-sectional (i.e., before
training) and longitudinal (i.e., changes due to intervention) relationships
between measures of standing balance, walking balance, and balance self-efficacy
versus long-distance walking function as measured via the 6-minute walk test
(6MWT). A regression model containing all three balance variables accounted for
60.8% of the variance in 6MWT performance (adj R (2) = .584; F(3,27) = 13.931; P
< .001); however, only dynamic balance (FGA) was an independent predictor (beta =
.502) of 6MWT distance. Interestingly, changes in balance were unrelated to
changes in the distance walked (each correlation coefficient <.17, P > .05). For
persons after stroke similar to those studied, improving balance may not be
sufficient to improve long-distance walking function.
PMID- 25120940
TI - Y-Stenting for Bifurcation Aneurysm Coil Embolization: What is the Risk?
AB - The use of two stents in a "Y" configuration (Y-stenting) to assist with coil
embolization of complex bifurcation aneurysms has been accepted as an alternative
to clip reconstruction of a select subset of challenging aneurysms. We review the
risks associated with Y-stenting, including its procedural complication rates,
angiographic occlusion rates, rerupture, and retreatment rates.
PMID- 25120941
TI - Deep brain stimulation for tremor associated with underlying ataxia syndromes: a
case series and discussion of issues.
AB - BACKGROUND: Deep brain stimulation (DBS) has been utilized to treat various
symptoms in patients suffering from movement disorders such as Parkinson's
disease, dystonia, and essential tremor. Though ataxia syndromes have not been
formally or frequently addressed with DBS, there are patients with ataxia and
associated medication refractory tremor or dystonia who may potentially benefit
from therapy. METHODS: A retrospective database review was performed, searching
for cases of ataxia where tremor and/or dystonia were addressed by utilizing DBS
at the University of Florida Center for Movement Disorders and Neurorestoration
between 2008 and 2011. Five patients were found who had DBS implantation to
address either medication refractory tremor or dystonia. The patient's underlying
diagnoses included spinocerebellar ataxia type 2 (SCA2), fragile X associated
tremor ataxia syndrome (FXTAS), a case of idiopathic ataxia (ataxia not otherwise
specified [NOS]), spinocerebellar ataxia type 17 (SCA17), and a senataxin
mutation (SETX). RESULTS: DBS improved medication refractory tremor in the SCA2
and the ataxia NOS patients. The outcome for the FXTAS patient was poor. DBS
improved dystonia in the SCA17 and SETX patients, although dystonia did not
improve in the lower extremities of the SCA17 patient. All patients reported a
transient gait dysfunction postoperatively, and there were no reports of
improvement in ataxia-related symptoms. DISCUSSION: DBS may be an option to treat
tremor, inclusive of dystonic tremor in patients with underlying ataxia; however,
gait and other symptoms may possibly be worsened.
PMID- 25120942
TI - Observational Study of IncobotulinumtoxinA for Cervical Dystonia or Blepharospasm
(XCiDaBLE): Interim Results for the First 170 Subjects with Blepharospasm.
AB - BACKGROUND: XCiDaBLE is a large, prospective, observational "naturalistic" study
evaluating Xeomin(r) for Cervical Dystonia or BLEpharospasm in the United States.
We report the interim results from the blepharospasm cohort of XCiDaBLE. METHODS:
Subjects (?18 years old) with blepharospasm were followed for two treatment
cycles of incobotulinumtoxinA and monitored for 4 weeks after injection via
interactive voice/web response system (IVRS/IWRS). The investigator-reported
scale includes the Clinical Global Impression Scale-Severity subscale (CGI-S).
Patient-reported outcome measures include the Patient Global Impression Scale
Severity (PGI-S) and -Improvement (PGI-I) subscales, Jankovic Rating Scale (JRS),
SF-12v2(r) health survey, and Work Productivity and Activity Impairment
questionnaire. Subjects are seen by the investigator at baseline (including the
first injection), during the second injection, and at a final study visit (12
weeks after the second injection). RESULTS: One hundred seventy subjects were
included in this interim analysis. The majority of subjects were female (77.1%)
and white (91.8%), and had previously been treated with botulinum toxins (96.5%).
The mean total dose (both eyes) was 71.5 U of incobotulinumtoxinA for the first
injection. PGI-S, PGI-I, and JRS scores were significantly improved 4 weeks after
treatment (all p<0.0001). No differences were noted in either quality of life
(QoL) or work productivity in this short assessment period. No unexpected adverse
events occurred. DISCUSSION: This is an interim study and assessment method based
on an IVRS/IWRS. In this predominantly toxin-experienced cohort, significant
benefits in specific and global measures of disease severity were seen in the
immediate post-incobotulinumtoxinA injection period. It will be interesting to
see if there are improvements in QoL with consistent individualized injections
over a longer period.
PMID- 25120944
TI - The GABA Hypothesis in Essential Tremor: Lights and Shadows.
AB - BACKGROUND: The gamma-aminobutyric acid (GABA) hypothesis in essential tremor
(ET) implies a disturbance of the GABAergic system, especially involving the
cerebellum. This review examines the evidence of the GABA hypothesis. METHODS:
The review is based on published data about GABA dysfunction in ET, taking into
account studies on cerebrospinal fluid, pathology, electrophysiology, genetics,
neuroimaging, experimental animal models, and human drug therapies. RESULTS:
Findings from several studies support the GABA hypothesis in ET. The hypothesis
follows four steps: 1) cerebellar neurodegeneration with Purkinje cell loss; 2) a
decrease in GABA system activity in deep cerebellar neurons; 3) disinhibition in
output deep cerebellar neurons with pacemaker activity; and 4) an increase in
rhythmic activity of the thalamus and thalamo-cortical circuit, contributing to
the generation of tremor. Doubts have been cast on this hypothesis, however, by
the fact that it is based on relatively few works, controversial post-mortem
findings, and negative genetic studies on the GABA system. Furthermore, GABAergic
drug efficacy is low and some GABAergic drugs do not have antitremoric efficacy.
DISCUSSION: The GABA hypothesis continues to be the most robust
pathophysiological hypothesis to explain ET. There is light in all GABA
hypothesis steps, but a number of shadows cannot be overlooked. We need more
studies to clarify the neurodegenerative nature of the disease, to confirm the
decrease of GABA activity in the cerebellum, and to test more therapies that
enhance the GABA transmission specifically in the cerebellum area.
PMID- 25120945
TI - The Non-motor Features of Essential Tremor: A Primary Disease Feature or Just a
Secondary Phenomenon?
AB - Essential tremor (ET) is a pathologically heterogeneous neurodegenerative
disorder with both motor and increasingly recognized non-motor features. It is
debated whether the non-motor manifestations in ET result from widespread
neurodegeneration or are merely secondary to impaired motor functions and
decreased quality of life due to tremor. It is important to review these features
to determine how to best treat the non-motor symptoms of patients and to
understand the basic pathophysiology of the disease and develop appropriate
pharmacotherapies. In this review, retrospective and prospective clinical studies
were critically analyzed to identify possible correlations between the severities
of non-motor features and tremor. We speculated that if such a correlation
existed, the non-motor features were likely to be secondary to tremor. According
to the current literature, the deficits in executive function, attention,
concentration, and memory often observed in ET are likely to be a primary
manifestation of the disease. It has also been documented that patients with ET
often exhibit characteristic personality traits. However, it remains to be
determined whether the other non-motor features often seen in ET, such as
anxiety, depression, and sleep disturbances are primary or secondary to motor
manifestations of ET and subsequent poor quality of life. Finally, there is
evidence that patients with ET can also have impaired color vision, disturbances
of olfaction, and hearing impairments, though there are few studies in these
areas. Further investigations of large cohorts of patients with ET are required
to understand the prevalence, nature, and true significance of the non-motor
features in ET.
PMID- 25120943
TI - Essential tremor: a neurodegenerative disease?
AB - BACKGROUND: Essential tremor (ET) is one of the most common neurological
disorders among adults, and is the most common of the many tremor disorders. It
has classically been viewed as a benign monosymptomatic condition, yet over the
past decade, a growing body of evidence indicates that ET is a progressive
condition that is clinically heterogeneous, as it may be associated with a
spectrum of clinical features, with both motor and non-motor elements. In this
review, I will describe the most significant emerging milestones in research
which, when taken together, suggest that ET is a neurodegenerative condition.
METHODS: A PubMed search conducted in June 2014 crossing the terms "essential
tremor" (ET) and "neurodegenerative" yielded 122 entries, 20 of which included
the term "neurodegenerative" in the article title. This was supplemented by
articles in the author's files that pertained to this topic. RESULTS/DISCUSSION:
There is an open and active dialogue in the medical community as to whether ET is
a neurodegenerative disease, with considerable evidence in favor of this.
Specifically, ET is a progressive disorder of aging associated with neuronal loss
(reduction in Purkinje cells) as well as other post-mortem changes that occur in
traditional neurodegenerative disorders. Along with this, advanced neuroimaging
techniques are now demonstrating distinct structural changes, several of which
are consistent with neuronal loss, in patients with ET. However, further
longitudinal clinical and neuroimaging longitudinal studies to assess progression
are required.
PMID- 25120946
TI - Mirror movements identified in patients with moebius syndrome.
AB - BACKGROUND: Moebius syndrome is a rare disorder with minimum clinical criteria of
congenital facial weakness in association with impairment in abduction of one or
both eyes. Mirror movements are not known to be associated with Moebius syndrome.
CASE REPORT: We present three patients who meet minimum criteria for a diagnosis
of Moebius syndrome and who also display mirror movements. DISCUSSION: This case
series suggests that Moebius syndrome may be associated with mirror movements.
Further investigation to delineate the genetic etiologies of Moebius syndrome is
ongoing. Patients with Moebius syndrome and mirror movements may represent a
specific subclass of this disorder.
PMID- 25120947
TI - Assessment of the effect of Schistosoma haematobium co infection on malaria
parasites and immune responses in rural populations in Gabon: study protocol.
AB - BACKGROUND: Malaria and helminth co infection are common in tropical and
subtropical areas where they affect the life of millions of people. While both
helminth and malaria parasites have immunomodulatory activities, little is known
about the consequence of co-infections on malaria antigen specific immune
responses. METHOD/DESIGN: This study will be conducted in two rural areas of the
Moyen Ogooue province in Gabon, endemic for both Plasmodium falciparum and
Schistosoma haematobium infections. Participants, 5 to 50 years old, will be
enrolled and grouped according to their infection status. S. haematobium and
malaria parasites will be detected, demographic and clinical data will be
recorded and blood will be collected for hematological as well as for
immunological assays. The level of antibody specific to Plasmodium falciparum
blood stage and gametocyte antigens will be measured using ELISA. PBMC will be
isolated for phenotyping of different T cell subsets ex vivo by flow cytometry
and for culture and cytokine response assessment. DISCUSSION: We will provide a
comprehensive picture of the interaction between schistosomes and malaria
parasites which co-localize in peripheral blood. We will test the hypothesis that
schistosome infection has an impact on specific humoral as well as on cellular
immune responses to malaria antigens.
PMID- 25120948
TI - Peroxidase activity in scutella of maize in association with anatomical changes
during germination and grain storage.
AB - The embryo of the maize grain (Zea mays L.) is separated from the starchy
endosperm by a fibrous structure, which is called the fibrous layer (FL). Using
histochemical staining, it was determined that the FL is composed of collapsed
cellular layers that contain phenols, neutral lipids, and 1,3-beta-glucan. Due to
its composition, the FL prevents free diffusion and separates the embryo from the
endosperm during germination. Twenty-four hours after imbibition, the scutellum
epidermis initiated a series of asynchronous spatial modifications, including
cell growth, the perforation of cell walls, increased peroxidase activity in the
apoplastic space, and elevated levels of superoxide, phenols, and other
components that interact with the fibrous layer, enabling its transformation in
addition to the free flow between compartments. During storage at high relative
humidity levels, which leads to fast or slow deterioration depending on the
temperature, the activity of phenol peroxidase in the scutellum was associated
with a loss of vigor and reduced germination capacity when compared with low
temperature and low relative humidity conditions. Such deterioration is
associated with alterations in autofluorescent emissions from endogenous
compounds in the scutellum, indicating changes in the microenvironment or in the
differential proportions of epidermal and FL components.
PMID- 25120950
TI - Pectoral nerves (PECS) and intercostal nerve block for cardiac resynchronization
therapy device implantation.
AB - A 71-year-old man was scheduled to undergo cardiac resynchronization therapy
device (CRTD) implantation. He was combined with severe chronic heart failure due
to ischemic heart disease. NYHA class was 3 to 4 and electrocardiogram showed non
sustained ventricular. Ejection fraction was about 20% revealed by transthoracic
echocardiogram. He was also on several anticoagulation medications. We planned to
implant the device under the greater pectoral muscle. As general anesthesia was
considered risky, monitored anesthesia care utilizing peripheral nerve block and
slight sedation was scheduled. Pectoral nerves (PECS) block and intercostal block
was performed under ultrasonography with ropivacaine. For sedation during the
procedure, continuous infusion of dexmedetomidine without a loading dose was
performed. The procedure lasted about 3 hours, but the patient showed no pain or
restlessness. Combination of PECS block and intercostal block may provide
effective analgesia for CRTD implantation.
PMID- 25120949
TI - Analyzing the efficiency of small and medium-sized enterprises of a national
technology innovation research and development program.
AB - This study analyzes the efficiency of small and medium-sized enterprises (SMEs)
of a national technology innovation research and development (R&D) program. In
particular, an empirical analysis is presented that aims to answer the following
question: "Is there a difference in the efficiency between R&D collaboration
types and between government R&D subsidy sizes?" Methodologically, the efficiency
of a government-sponsored R&D project (i.e., GSP) is measured by Data Envelopment
Analysis (DEA), and a nonparametric analysis of variance method, the Kruskal
Wallis (KW) test is adopted to see if the efficiency differences between R&D
collaboration types and between government R&D subsidy sizes are statistically
significant. This study's major findings are as follows. First, contrary to our
hypothesis, when we controlled the influence of government R&D subsidy size,
there was no statistically significant difference in the efficiency between R&D
collaboration types. However, the R&D collaboration type, "SME-University
Laboratory" Joint-Venture was superior to the others, achieving the largest
median and the smallest interquartile range of DEA efficiency scores. Second, the
differences in the efficiency were statistically significant between government
R&D subsidy sizes, and the phenomenon of diseconomies of scale was identified on
the whole. As the government R&D subsidy size increases, the central measures of
DEA efficiency scores were reduced, but the dispersion measures rather tended to
get larger.
PMID- 25120952
TI - Corrigendum: glycobiology of neuroblastoma: impact on tumor behavior, prognosis,
and therapeutic strategies.
PMID- 25120951
TI - Yttrium-90 radioembolization of hepatic metastases from colorectal cancer.
AB - Liver metastases from colorectal cancer (CRC) result in substantial morbidity and
mortality. The primary treatment is systemic chemotherapy, and in selected
patients, surgical resection; however, for patients who are not surgical
candidates and/or fail systemic chemotherapy, liver-directed therapies are
increasingly being utilized. Yttrium-90 (Y-90) microsphere therapy, also known as
selective internal radiation therapy (SIRT) or radioembolization, has proven to
be effective in terms of extending time to progression of disease and also
providing survival benefit. This review focuses on the use of Y-90 microsphere
therapy in the treatment of liver metastases from CRC, including a comprehensive
review of published clinical trials and prospective studies conducted thus far.
We review the methodology, outcomes, and side effects of Y-90 microsphere therapy
for metastatic CRC.
PMID- 25120954
TI - X-linked inhibitor of apoptosis protein - a critical death resistance regulator
and therapeutic target for personalized cancer therapy.
AB - Defects in apoptosis regulation are one main cause of cancer development and may
result from overexpression of anti-apoptotic proteins such as inhibitor of
apoptosis proteins (IAPs). IAPs are cell death regulators that, among other
functions, bind caspases, and interfere with apoptotic signaling via death
receptors or intrinsic cell death pathways. All IAPs share one to three common
structures, the so called baculovirus-IAP-repeat (BIR)-domains that allow them to
bind caspases and other proteins. X-linked inhibitor of apoptosis protein (XIAP)
is the most potent and best-defined anti-apoptotic IAP family member that
directly neutralizes caspase-9 via its BIR3 domain and the effector caspases-3
and -7 via its BIR2 domain. A natural inhibitor of XIAP is SMAC/Diablo, which is
released from mitochondria in apoptotic cells and displaces bound caspases from
the BIR2/BIR3 domains of XIAP thereby reactivating cell death execution. The
central apoptosis-inhibitory function of XIAP and its overexpression in many
different types of advanced cancers have led to significant efforts to identify
therapeutics that neutralize its anti-apoptotic effect. Most of these drugs are
chemical derivatives of the N-terminal part of SMAC/Diablo. These "SMAC-mimetics"
either specifically induce apoptosis in cancer cells or act as drug-sensitizers.
Several "SMAC-mimetics" are currently tested by the pharmaceutical industry in
Phase I and Phase II trials. In this review, we will discuss recent advances in
understanding the function of IAPs in normal and malignant cells and focus on
approaches to specifically neutralize XIAP in cancer cells.
PMID- 25120955
TI - Side effects of yttrium-90 radioembolization.
AB - Limited therapeutic options are available for hepatic malignancies. Image guided
targeted therapies have established their role in management of primary and
secondary hepatic malignancies. Radioembolization with yttrium-90 ((90)Y)
microspheres is safe and efficacious for treatment of hepatic malignancies. The
tumoricidal effect of radioembolization is predominantly due to radioactivity and
not ischemia. This article will present a comprehensive review of the side
effects that have been associated with radioembolization using (90)Y
microspheres. Some of the described side effects are associated with all
transarterial procedures. Side effects specific to radioembolization will also be
discussed in detail. Methods to decrease the incidence of these potential side
effects will also be discussed.
PMID- 25120956
TI - Advancements toward a systems level understanding of the human oral microbiome.
AB - Oral microbes represent one of the most well studied microbial communities owing
to the fact that they are a fundamental part of human development influencing
health and disease, an easily accessible human microbiome, a highly structured
and remarkably resilient biofilm as well as a model of bacteria-bacteria and
bacteria-host interactions. In the last 80 years since oral plaque was first
characterized for its functionally stable physiological properties such as the
highly repeatable rapid pH decrease upon carbohydrate addition and subsequent
recovery phase, the fundamental approaches to study the oral microbiome have
cycled back and forth between community level investigations and characterizing
individual model isolates. Since that time, many individual species have been
well characterized and the development of the early plaque community, which
involves many cell-cell binding interactions, has been carefully described. With
high throughput sequencing enabling the enormous diversity of the oral cavity to
be realized, a number of new challenges to progress were revealed. The large
number of uncultivated oral species, the high interpersonal variability of
taxonomic carriage and the possibility of multiple pathways to dysbiosis pose as
major hurdles to obtain a systems level understanding from the community to the
gene level. It is now possible however to start connecting the insights gained
from single species with community wide approaches. This review will discuss some
of the recent insights into the oral microbiome at a fundamental level, existing
knowledge gaps, as well as challenges that have surfaced and the approaches to
address them.
PMID- 25120953
TI - Genomic Analysis as the First Step toward Personalized Treatment in Renal Cell
Carcinoma.
AB - Drug resistance mechanisms in renal cell carcinoma (RCC) still remain elusive.
Although most patients initially respond to targeted therapy, acquired resistance
can still develop eventually. Most of the patients suffer from intrinsic
(genetic) resistance as well, suggesting that there is substantial need to
broaden our knowledge in the field of RCC genetics. As molecular abnormalities
occur for various reasons, ranging from single nucleotide polymorphisms to large
chromosomal defects, conducting whole-genome association studies using high
throughput techniques seems inevitable. In principle, data obtained via genome
wide research should be continued and performed on a large scale for the purposes
of drug development and identification of biological pathways underlying
cancerogenesis. Genetic alterations are mostly unique for each histological RCC
subtype. According to recently published data, RCC is a highly heterogeneous
tumor. In this paper, the authors discuss the following: (1) current state-of-the
art knowledge on the potential biomarkers of RCC subtypes; (2) significant
obstacles encountered in the translational research on RCC; and (3) recent
molecular findings that may have a crucial impact on future therapeutic
approaches.
PMID- 25120959
TI - Fungal-bacterial interactions and their relevance to oral health: linking the
clinic and the bench.
AB - High throughput sequencing has accelerated knowledge on the oral microbiome.
While the bacterial component of oral communities has been extensively
characterized, the role of the fungal microbiota in the oral cavity is largely
unknown. Interactions among fungi and bacteria are likely to influence oral
health as exemplified by the synergistic relationship between Candida albicans
and oral streptococci. In this perspective, we discuss the current state of the
field of fungal-bacterial interactions in the context of the oral cavity. We
highlight the need to conduct longitudinal clinical studies to simultaneously
characterize the bacterial and fungal components of the human oral microbiome in
health and during disease progression. Such studies need to be coupled with
investigations using disease-relevant models to mechanistically test the
associations observed in humans and eventually identify fungal-bacterial
interactions that could serve as preventive or therapeutic targets for oral
diseases.
PMID- 25120961
TI - Morphological study of dendritic cells in human cervix by zinc iodide osmium
method.
AB - BACKGROUND: Dendritic cells (DCs) are a heterogeneous population of antigen
presenting cells that have been identified in several tissues including the
female reproductive organs. The aim of the present study is to demonstrate the
morphological differences of dendritic cells in normal human exocervix using the
Zinc Iodide Osmium (ZIO) procedure. MATERIALS AND METHODS: Normal cervical
tissues obtained from nine patients who underwent abdominal hysterectomies for
various ailments were processed for histochemical study. Six microns thick serial
sections were taken and viewed under a light microscope. The diameters of the
cells were measured under a magnification of 40x using the Cellsens image
analysing software and analysed using SPSS version 16. RESULTS AND CONCLUSION: In
the normal human exocervix, a greater density of ZIO-positive DCs was noted in
the epithelium and subepithelium and their distribution was not uniform. In some
areas of epithelium, the ZIO-positive cells in the basal layer showed a typical
dendritic morphology, while the cells in the intermediate and superficial layers
were nondendritic polygonal cells. Intraepithelial capillaries were noted, which
were surrounded by ZIO-positive nondendritic polygonal cells. There was
significant difference in the mean diameters of typical DCs (8.61+/-1.86 MUm) and
nondendritic polygonal cells (10.97+/-1.93 MUm). In the subepithelium the DCs had
typical morphology and their distribution varied. ZIO positive DCs were noted in
the epithelium and cervical glands of endocervix also. In conclusion, the human
cervix has different subsets of ZIO positive DCs with varied distribution. Their
functional role has yet to be defined.
PMID- 25120962
TI - Evaluation of Fetal Central Nervous System Anomalies by Ultrasound and Its
Anatomical Co-relation.
AB - INTRODUCTION: Central nervous system anomalies are often severe and are the most
common indications for therapeutic abortions. Ultrasound examination helps to
identify and evaluate them well before birth. OBJECTIVES: Present study was
undertaken to evaluate the incidence of central nervous system anomalies in utero
by ultrasound and to confirm them by autopsy or postnatal examination. METHOD:
Ultrasound screening of 7485 pregnant women was performed. Pregnancy with
ultrasound findings of central nervous system anomalies were followed up.
Prenatal ultrasound findings were confirmed by autopsy in cases of therapeutic
abortions and fetal losses. In case of live birth postnatal findings were noted.
RESULTS: Ultrasound detected central nervous system malformations in 24 fetuses.
Ultrasound findings were matching in 83% on autopsy. Autopsy and postnatal
findings together were matching with ultrasound in 85.7%. Two cases had
additional minor findings on autopsy. CONCLUSION: The incidence of central
nervous system malformations on ultrasound was 0.31%. Autopsy and postnatal
examination showed high degree of correlation with ultrasound findings.
PMID- 25120958
TI - Pathogenesis of cerebral malaria--inflammation and cytoadherence.
AB - Despite decades of research on cerebral malaria (CM) there is still a paucity of
knowledge about what actual causes CM and why certain people develop it. Although
sequestration of P. falciparum infected red blood cells has been linked to
pathology, it is still not clear if this is directly or solely responsible for
this clinical syndrome. Recent data have suggested that a combination of parasite
variant types, mainly defined by the variant surface antigen, P. falciparum
erythrocyte membrane protein 1 (PfEMP1), its receptors, coagulation and host
endothelial cell activation (or inflammation) are equally important. This makes
CM a multi-factorial disease and a challenge to unravel its causes to decrease
its detrimental impact.
PMID- 25120957
TI - Staphylococcus aureus Small Colony Variants (SCVs): a road map for the metabolic
pathways involved in persistent infections.
AB - Persistent and relapsing infections, despite apparently adequate antibiotic
therapy, occur frequently with many pathogens, but it is an especially prominent
problem with Staphylococcus aureus infections. For the purposes of this review,
persistence will encompass both of the concepts of long term survival within the
host, including colonization, and the concept of resisting antibiotic therapy
even when susceptible in the clinical microbiology laboratory. Over the past two
decades, the mechanisms whereby bacteria achieve persistence are slowly being
unraveled. S. aureus small colony variants (SCVs) are linked to chronic,
recurrent, and antibiotic-resistant infections, and the study of SCVs has
contributed significantly to understanding of persistence. In our earlier work,
defects in electron transport and thymidylate biosynthesis were linked to the
development of the SCV phenotype (reviewed in 2006), thus this work will be
discussed only briefly. Since 2006, it has been found that persistent organisms
including SCVs are part of the normal life cycle of bacteria, and often they
arise in response to harsh conditions, e.g., antibiotics, starvation, host
cationic peptides. Many of the changes found in these early SCVs have provided a
map for the discovery mechanisms (pathways) for the development of persistent
organisms. For example, changes in RNA processing, stringent response, toxin
antitoxin, ribosome protein L6 (RplF), and cold shock protein B (CspB) found in
SCVs are also found in other persisters. In addition, many classic persister
organisms also show slow growth, hence SCVs. Recent work on S. aureus USA300 has
elucidated the impact of aerobic expression of arginine deiminase genes on its
ability to chronically colonize the skin and survive in abscesses. S. aureus SCVs
also express arginine deiminase genes aerobically as well. Thus, many pathways
found activated in electron transport type of SCVs are also increased in
persisters that have intact electron transport. Many of these changes in
metabolism result in slow growth; hence, small colonies are formed. Another
common theme is that slow growth is also associated with reduced expression of
virulence factors and enhanced uptake/survival within host cells. These
adaptations to survive within the host are rooted in responses that were required
for organisms to survive in a harsh environment long before they were mammals on
the earth.
PMID- 25120964
TI - Anomalous Branching Pattern of the Popliteal Artery (PA): A Case Report.
AB - The Popliteal Artery (PA), which is the continuation of the Femoral artery,
crosses the popliteal fossa at the distal border of popliteus; it divides into
the Anterior and Posterior Tibial arteries. The Posterior Tibial Artery (PTA)
divides into terminal branches proximal to popliteus, in which case the Anterior
Tibial Artery (ATA) sometimes descends anterior to the muscle. Either the
Anterior tibial or the PTA may be reduced or increased in size. The dorsalis
pedis artery (DPA) is the continuation of the ATA, distal to the ankle. It passes
to the proximal end of the first intermetatarsal space, to complete the plantar
arch, and provides the first plantar metatarsal artery. In the present case the
PA bifurcates into two terminal branches at a higher level than the normal. The
ATA was hypo plastic and entered the anterior crural region in front of the
popliteus muscle and finally terminated above the knee joint. Further the PTA was
also hypo plastic giving off a hyperplastic PL which pierced the interosseous
membrane and on entering the dorsum of the foot, it prolonged as the DPA. The
rest of the PTA continued its course distally and divided into its usual
branches, the medial and lateral planter arteries. Awareness of these variations
in the vascular branching patterns of the lower limb, acts as a guide during
femero distal bypass grafting procedures and surgical and percutaneous vascular
reconstructions.
PMID- 25120960
TI - High-throughput screening of tick-borne pathogens in Europe.
AB - Due to increased travel, climatic, and environmental changes, the incidence of
tick-borne disease in both humans and animals is increasing throughout Europe.
Therefore, extended surveillance tools are desirable. To accurately screen tick
borne pathogens (TBPs), a large scale epidemiological study was conducted on 7050
Ixodes ricinus nymphs collected from France, Denmark, and the Netherlands using a
powerful new high-throughput approach. This advanced methodology permitted the
simultaneous detection of 25 bacterial, and 12 parasitic species (including;
Borrelia, Anaplasma, Ehrlichia, Rickettsia, Bartonella, Candidatus Neoehrlichia,
Coxiella, Francisella, Babesia, and Theileria genus) across 94 samples. We
successfully determined the prevalence of expected (Borrelia burgdorferi sensu
lato, Anaplasma phagocytophilum, Rickettsia helvetica, Candidatus Neoehrlichia
mikurensis, Babesia divergens, Babesia venatorum), unexpected (Borrelia
miyamotoi), and rare (Bartonella henselae) pathogens in the three European
countries. Moreover we detected Borrelia spielmanii, Borrelia miyamotoi, Babesia
divergens, and Babesia venatorum for the first time in Danish ticks. This
surveillance method represents a major improvement in epidemiological studies,
able to facilitate comprehensive testing of TBPs, and which can also be
customized to monitor emerging diseases.
PMID- 25120963
TI - Radiographical study showing asymmetry in the surface area of carpal bones in
malnourished children.
AB - BACKGROUND: Protein energy malnutrition, a major health and nutritional problem
in India, leads to retardation in bone maturity and eventually physical growth.
Many studies have been done on ossification centers of hand bones for estimation
of skeletal maturation and to diagnose malnutrition but very few studies have
been done so far to see effect of protein energy malnutrition on surface area of
carpal bones. AIMS AND OBJECTIVES: The surface areas of carpal bones on
radiographs on both sides were calculated, analysed and compared in protein
energy malnutrition (PEM) cases and healthy controls upto five years of age to
see the variability among study groups. MATERIALS AND METHODS: The study was
conducted in Department of Paediatrics, Radiodiagnosis and Anatomy of S.N.
Medical College, Agra, India consisting of 68 PEM cases and 68 controls of either
sex upto five years of age. Radiography of wrist done and surface areas of carpal
bones were calculated by using millimeter Graph Transparency paper by Hit method
and data were evaluated for significance by using t-test. RESULT: The surface
areas of capitate, hamate and triquetral bones of both hands were reduced in PEM
children of all grades as compared to healthy controls. The surface areas of
these carpal bones were much reduced in grade 2 and grade 3 PEM cases as compared
to healthy controls and grade 1 PEM cases. Asymmetry in surface areas of capitate
and hamate bones were ascertained in healthy controls and grade 1 PEM cases but
due to delay in appearance of ossification centers and reduced surface areas of
these bones, asymmetry could not be ascertained in grade 2 and grade 3
malnutrition children. CONCLUSION: The surface areas of capitate, hamate and
triquetral bones on both sides were reduced in grade 2 and grade 3 PEM cases as
compared to controls. Asymmetry in surface area of carpal bones was ascertained
in healthy controls and grade 1 PEM cases.
PMID- 25120966
TI - Foot index in right footed adults.
PMID- 25120965
TI - Anatomical variation: median nerve formation - a case vignette.
AB - Variations in the arrangement and distribution of brachial plexus and its
branches in the infraclavicular part are common and have been reported by several
investigators since the 19th century. These variations are significant for the
neurologists, surgeons, anesthetists and the anatomists. During routine
anatomical dissection of the right axilla and infraclavicular region of a 45-year
old male cadaver, the medial root of the median nerve was found to receive a
supplementary branch from the medial aspect of the terminal portion of the
lateral cord of brachial plexus and the branch was passing infront of the
axillary artery from lateral to medial side. The median nerve was formed by
joining of the lateral and medial roots from the lateral and medial cords of
brachial plexus, infront of brachial artery, lower down, at the junction of upper
one-third and lower two-third of the arm, instead in the axilla. This variation
could be one of the cause of pressure symptom which occurs on the axillary artery
and also the injury which occurs on the lateral cord or upstream to the lateral
cord, which may sometimes lead to an unexpected presentation of weakness of
forearm flexors and thenar muscles.
PMID- 25120967
TI - Study of cardiovascular reactivity to mental stress in different phases of
menstrual cycle.
AB - BACKGROUND: It is a well known fact that normally female sex hormone levels
fluctuate during the menstrual cycle. The presence of receptors for these
hormones on both heart and blood vessels may also hint at variations in
physiological functions during menstrual cycle. So this study was an attempt to
determine whether the follicular and luteal phases of menstrual cycle are
characterized by variations in cardiovascular parameters in the resting state and
also examine changes in cardiovascular reactivity to mental stress challenge
during both the phases of menstrual cycle. METHODOLOGY: Thirty healthy females in
the age group of 18-25 years with regular menstrual cycles fulfilling the
inclusion criteria were examined for cardiovascular parameters (heart rate and
blood pressures) at rest and their reactivity to mental stress during the
follicular and luteal phase and were compared by using paired t-test. A p-value
of <0.05 was considered as statistically significant. RESULTS: The women included
in the study produced the well known reactivity to mental stress, in terms of
blood pressure and heart rate increases, but the two phases of menstrual cycle
were indistinguishable in so far as reactivity patterns were considered. The
resting values of these cardiovascular parameters were also alike during the two
phases. CONCLUSION: We were unable to unearth any differences in resting and
reactivity values of cardiovascular parameters during the course of a normal
menstrual cycle. This shows that stress reactivity variations during different
phases of menstrual cycle may not be due to variations in hormonal levels per se,
but due to collusion of hormonal variations and unknown genetic influences.
PMID- 25120968
TI - Alteration of Interferon Gamma (IFN-gamma) in Human Plasma with Graded Physical
Activity.
AB - INTRODUCTION: Practice of regular exercise is beneficial for health. Physical
exercises have been demonstrated to alter levels of the cytokine interferon Gamma
in plasma. IFN-gamma is known to be an anti-inflammatory cytokine. MATERIALS AND
METHODS: We assessed the effect of single bout of moderate exercise and a single
bout of strenuous exercise and one month of regular moderate exercise on plasma
IFN-gamma. The study consisted of 18 healthy volunteers (10 males and 8 females)
with the mean age, 20.94 years, range, 18-25 years. The exercise regime adopted
is the standardized 10m Shuttle Walk Test regime. IFN-gamma was estimated using
the Sandwich ELISA technique. The reagent kit was obtained from Duoset ELISA
Development System of R & D Systems Europe Ltd. The readings were taken at 450nm
using Organon Teknika Reader 230S. STATISTICAL METHODS: Friedman test has been
used for analysing IFN-gamma values. RESULTS: Mean and SD values of IFN-gamma (in
picograms per ml) for baseline (no exercise) was: 54.56 +/- 28.54 (log
transformation: 1.68+/-0.23), for acute moderate exercise: 28.94 +/- 38.46 (log
transformation: 1.34 +/- 0.24), for acute strenuous exercise: 20.06 +/- 16.96
(log transformation: 1.18 +/-0.33) and after one month of regular moderate
exercise: 106.33 +/- 21.51 (log transformation: 2.02 +/- 0.09). The change in IFN
gamma levels showed significant difference between; a) baseline and moderate
exercise, b) baseline and strenuous exercise, c) moderate and strenuous exercise,
d) strenuous exercise and end of one month of regular moderate exercise, e)
baseline and end of one month of regular moderate exercise, f) moderate exercise
and end of one month of regular moderate exercise. IFN-gamma showed overall
significance between different grades of exercise (p < 0.05). CONCLUSION: Plasma
IFN-gamma decreases with one bout of acute moderate exercise, it decreases
further with one bout of acute strenuous exercise and increases at end of one
month of regular moderate exercise, which is more than baseline value. This shows
that regular moderate exercise has beneficial effects on health by way of
increasing plasma IFN-gamma level.
PMID- 25120969
TI - Effect of age and Blood Pressure on Surrogate Markers of Atherosclerosis in
Patients with Type 2 Diabetes Mellitus.
AB - BACKGROUND: Increased arterial stiffness may be an important path- way linking
diabetes mellitus to increased cardiovascular risk. AIM: The study was conducted
to assess the surrogate markers of arterial stiffness in patients with Type 2
diabetes mellitus (T2DM), and compare with age-matched hypertensive and healthy
controls. Also the effect of age and blood pressure on these markers was
evaluated. SETTINGS AND DESIGN: This cross-sectional study was carried out at a
tertiary care hospital in West India. METHODS: After a detailed medical history
and anthropometric evaluation, all the participants were subjected to
measurements of Arterial Stiffness Index (ASI), Pulse Wave Velocity (PWV), and
Augmentation Index (AIx) using a non-invasive oscillometric method. The four
study groups consisted of patients with T2DM (>5 years) along with hypertension,
newly diagnosed patients with T2DM (<2years) without hypertension, hypertensive
controls, and healthy controls. RESULTS: PWV, ASI, AIx were elevated in patients
with T2DM compared to healthy controls (p<0.05). Patients with T2DM above 60
years had higher carotid-femoral PWV, ASI and AIx than those below 60 years
(p<0.05). ASI and AIx were significantly increased in patients with T2DM with
hypertension having systolic BP > 140 mmHg compared to those with systolic BP <
140 mmHg. A very strong correlation between PWV and AIx in patients with T2DM and
hypertensive controls was observed. CONCLUSION: This study reveals that markers
of arterial stiffness (PWV, ASI, AIx) were increased significantly in patients
with T2DM compared to healthy controls. Age and systolic blood pressure had
significant influence on these markers. Thus, oscillometric markers have
potential utility in identifying subclinical atherosclerosis in patients with
T2DM.
PMID- 25120970
TI - Comparison of cognitive functions between male and female medical students: a
pilot study.
AB - BACKGROUND: There are gender differences in cognitive abilities. The major enigma
is whether males or females perform better in various cognitive tasks. The
reports were found to be contradictory. Studies have shown that oestrogen and
testosterone accentuate cognitive functions. But the effects of progesterone on
cognitive functions are still contradictory. OBJECTIVE: To assess and compare the
cognitive functions between male and female students. METHODS: This study was
conducted on healthy male (n=21) and female (n=21) volunteers who were aged
between 19-37 years. Cognitive functions which were assessed in males (one time)
and females (two times: during preovulatory and postovulatory phases of the
menstrual cycle) were attentional: visual reaction time (VRT) and Go/No-Go VRT;
perceptual: fast counting (FC), executive: Erisken Flanker Test (EFT) and Stroop
Test (ST), and working memory. Data were compared by using Mann-Whitney U-test.
RESULTS: Cognitive functions in female preovulatory phase were comparable to male
cognitive functions. In addition, the female postovulatory phase cognitive
functions were also similar to those of males in all the tasks, except those seen
in VRT and ST. Male performed better than females in VRT (M: 331.66 ms, IQR:
286.99-375.33 vs. M: 367.8 ms, IQR: 340.66-435.66; p=0.05). However, in ST,
females showed higher accuracies in reading colour interferences than males (M:
100%, IQR: 95.12-100 vs. M: 95.24%, IQR: 86.36-100; p=0.04). In addition, males
showed trend of a poorer performance than females in Go/No-Go VRT, ST colour
reading normal time and interference time and in working-memory time. CONCLUSION:
Male cognitive functions were comparable to female preovulatory phase cognitive
functions. However, females, during postovulatory phase of their cycle, may have
advantages in executive tasks (Stroop test) and disadvantages in attentional
tasks (VRT), as compared to males.
PMID- 25120971
TI - Brainstem Auditory Evoked Potentials (BAEP)- A Pilot Study Conducted on Young
Healthy Adults from Central India.
AB - OBJECTIVE: To Evaluate I, II, III, IV, V wave latencies and I-III, III-V, I-V
inter-peak latencies and V/I wave amplitude ratio in Normal subjects in Central
India. METHODS: We recorded BAEP from 50 healthy normal subjects from the
community of same sex and geographical setup. The absolute, interpeak and wave
V/I amplitude ratio were measurement and recording was done using RMS EMG EP MARK
II machine manufactured by RMS recorders and Medicare system, Chandigarh. RESULT:
Absolute, interpeak and wave V/I amplitude ratio were measured in normal subjects
and compared with other previous studies. CONCLUSION: This study was conducted as
exploratory pilot study only on male healthy controls. Since, the study conducted
in different regions, there are some differences in the latencies and interpeak
latencies and amplitude ratio but they are within range, so reference range of
this study can be used for future studies in this Wardha region of Central India.
PMID- 25120972
TI - Study of Cholesteryl Ester Transfer Protein (CETP) I405v Genotype and Its
Association with Lipid Fractions in Myocardial Infarction Patients: A Case
Control Study.
AB - OBJECTIVES: We determine the significant relation of HDL cholesterol and total
cholesterol/HDL cholesterol between CETP I405V genotypes and activity of CETP.
CETP is an essential for transfer of cholesterol ester to the liver from
peripheral tissues which facilitating its transfer to TG rich VLDL. Reduction
activity of CETP I405V may associate with genotypes of CETP I405V. This study is
undertaken to assess the presence and impact of CETP I405V genotype in our
population. MATERIALS AND METHODS: In this study 100 acute myocardial infarction
patients and 100 normal age & sex matched healthy individuals were included.
Serum Lipid profile was estimated by using universal standard methods whereas
CETP I405V genotype was studied by ARMS PCR. RESULT: There is presence of CETP
405Val genotype both in patient as well as in control group. RESULTs show that
HDL cholesterol (p<0.0001) and ratio of total cholesterol/HDL cholesterol are
significantly (p<0.0043) associated with Val/Val genotype. In addition to that
the CETP I405V genotype is associated with inhibition of CETP activity with
higher HDL-C level and decreased total cholesterol/HDL cholesterol ratio.
CONCLUSION: Our results show that the CETP I405V genotypes are very much
significantly determinant of HDL cholesterol in patients with CHD.
PMID- 25120973
TI - Validation of Method Performance of pH, PCO2, PO2, Na(+), K(+) of Cobas b121 ABG
Analyser.
AB - INTRODUCTION: The introduction of a new method or new analyser is a common
occurrence in clinical biochemistry laboratory. Blood gas measurements and
electrolytes are often performed in Point-of-Care (POC) settings. When a new POC
analyser is obtained, the performance of the analyser should be evaluated by
comparison to the measurements with the reference analyser in the laboratory.
OBJECTIVES: Evaluation of method performance of pH, PCO2, PO2, Na(+), K(+) of
cobas b121 ABG analyser. MATERIALS & METHODS: The evaluation of method
performance of pH, PO2, PCO2, Na(+), K(+) of cobas b121 ABG analyser was done by
comparing the results of 50 patient samples run on cobas b121 with the results
obtained from Rapid lab values (reference analyser). Correlation coefficient was
calculated from the results obtained from both the analysers. Precision was
calculated by running biorad ABG control samples. RESULTS: The correlation
coefficient values obtained for parameters were close to 1.0 indicating good
correlation. The CV obtained for all the parameters were less than 5 indicating
good precision. CONCLUSION: The new ABG analyser, Cobas b121 correlated well with
the reference ABG analyser (Rapid Lab) and could be used to run on patient
samples.
PMID- 25120974
TI - Correlation of Plasma Lipid Profile with Salivary Oxidative Stress Markers in
Type II Diabetes Mellitus Patients.
AB - INTRODUCTION: Diabetes is known to be associated with greater production of
reactive oxygen species (ROS) like malondialdehyde (MDA) and decreased
antioxidants like total thiols and its estimation in plasma is used in monitoring
the redox status. The aim of this study was to analyse the association between
plasma lipid profile parameters like HDL and LDL with salivary MDA and thiols in
diabetic patients. MATERIALS AND METHODS: Sixty subjects between the age group 35
70 years who were diagnosed with type II diabetes mellitus based on fasting
blood glucose and glycated haemoglobin levels who attended the dental OPD at
Kasturba Medical College and Hospital, Manipal consented to participate in this
study. Plasma glucose, HDL and LDL were estimated in Cobas autoanalyser by
hexokinase method, homogenous enzymatic colorimetric assay and Friedwald's
formula respectively. Assessment of glycated hemoglobin was by ion exchange
chromatography, MDA by thiobarbituric acid as a substrate and thiols by Ellmann's
manual method in plasma and saliva. RESULTS: The association of plasma LDL with
salivary MDA was found to be positive and significant and that with salivary
thiols was negative and significant. Also, the association of plasma HDL with
salivary MDA was found to be negative and significant and that with salivary
thiols was positive and significant. CONCLUSION: RESULTS indicate the potential
of saliva as a tool to monitor prognosis of diabetes.
PMID- 25120975
TI - Association of high sensitivity C-reactive protein with the components of
metabolic syndrome in diabetic and non-diabetic individuals.
AB - BACKGROUND AND OBJECTIVES: High sensitivity C-reactive protein (hsCRP) has been
associated with metabolic syndrome (MetS) and its components. Several studies
have suggested hsCRP to be used as a marker for the primary prevention of
cardiovascular diseases. So, we aimed to evaluate the association between hsCRP
levels and the components of MetS in diabetic and non-diabetic population.
MATERIALS AND METHODS: Type II diabetic patients (T2DM) (n= 121) and healthy
controls (n= 121) were enrolled for the study. Anthropometric measurements were
taken along with blood pressure from the arm. Ten ml of blood was collected after
overnight fasting for the measurement of lipid profile, hsCRP, C-peptide and
glucose levels. Insulin resistance (HOMA2-IR) was estimated by HOMA2 calculator
utilizing glucose and C-peptide values. All participants were classified into two
groups on the basis of the presence or absence of MetS. Data were analysed
through SPSS 14 software. RESULTS: hsCRP, C-peptide and HOMA2-IR were
significantly higher in T2DM subjects when compared with controls. As the number
of the components of MetS increased, there was a linear increase in hsCRP levels
in whole study population (p trend <.001), diabetic subjects (p trend <.001), as
well as in controls (p trend <.001). HOMA2-IR and hsCRP levels were found to be
better than LDL cholesterol and waist circumference for predicting the presence
of MetS. CONCLUSION: hsCRP was found to be better than LDL cholesterol and waist
circumference for the prediction of MetS. Hence, hsCRP could be used as a
defining marker of MetS in the near future.
PMID- 25120976
TI - Emergence of Escherichia coli, Co-Producing NDM-1 and OXA-48 Carbapenemases, in
Urinary Isolates, at a Tertiary Care Centre at Central India.
AB - OBJECTIVE: To detect genes encoding carbapenem resistance in urinary isolates of
Escherichia coli recovered from hospitalized patients in tertiary care centre in
Pune, India. METHODS: From Jan 2012 to Dec 2012, a total of 300 consecutive non
duplicate (one isolate per patient) clinical isolates of Escherichia coli were
recovered from urine cultures of hospitalized patients including hospital
acquired infection cases admitted to the medical and surgical intensive care
units. Polymerase chain reaction (PCR) assays and sequencing was used to
determine the presence of beta-lactamase encoding genes. Conjugation experiments
were performed to determine the transferability of beta-lactamase. RESULTS: All
the isolates were completely resistant to the second and third generation
cephalosporins tested as well as carbapenems. All the isolates showed 100%
susceptibility to tigecycline and colistin in vitro. Conjugation experiments
demonstrated that blaNDM-1 was transferable via plasmid. All the isolates showed
presence of blaNDM-1 and co-association of blaOXA-48 was 25/45(55%) of the
isolates. Repetitive element based PCR (REP PCR), Enterobacterial Repetitive
Intergenic Consensus (ERIC PCR) and Randomly Amplified Polymorphic DNA (RAPD)
revealed a diversity of six clonal types among E.coli isolates. CONCLUSION: Co
production of NDM-1with OXA-48 in urinary isolates of E. coli was detected for
the first time in India. Transmission of plasmid carrying these resistant genes
to other members of Enterobacteriaceae will increase incidence of multidrug
resistance. Early detection of these genes will help in prevention and adequate
infection control by limiting the spread of these organisms.
PMID- 25120977
TI - Comparision of Three Laboratory Tests for Detection of AmpC beta Lactamases in
Klebsiella Species and E. Coli.
AB - BACKGROUND AND OBJECTIVE: AmpC beta lactamases are one of the important causes of
drug resistance in gram negative bacteria. Failure to detect these enzymes in the
laboratory has contributed to therapeutic failures but there are till date no
standard guideline available. This study was therefore undertaken to evaluate
three phenotypic laboratory tests and the inhibitors used in two of the tests to
detect AmpC beta lactamases produced by E. coli and Klebsiella species as they
are most commonly isolated organisms. METHODS: E. coli and Klebsiella isolates
from different clinical samples were tested for ESBLs production as per CLSI
guidelines and excluded from the study. The non-ESBLs isolates were then screened
for AmpC beta lactamases production, by cefoxitin and then confirmed by three
different methods, i.e., Disc Potentiation Test (DPT) , Double Disc Synergy Test
(DDST) and Modified Three Dimensional Test (M3DT) which in the absence of
molecular methods, was taken as the gold standard. Boronic acid and cloxacillin
were used as inhibitory agents in the Disc Potentiation and Double Disc synergy
Tests. RESULTS: A total of 2,933 isolates were tested out of which 165 isolates
were detected as non ESBLs producers,135 (81.82%) when screened for AmpC beta
lactamases based on resistance to cefoxitin were labelled as positive. 30
(18.18%) cefoxitin sensitive isolates were labelled as probably non AmpC
producers . M3DT, in addition to detecting all the 135 (100%) cefoxitin resistant
isolates, also detected 5 (16.67%) cefoxitin sensitive isolates as AmpC
producers. Other phenotypic tests, DPT and DDST with different inhibitors like
boronic acid and cloxacillin in different potencies were all found to be less
sensitive. The best results among these two methods were obtained with DDST using
cloxacillin 500MUg. CONCLUSION: In the absence of recommended guidelines for AmpC
detection, the study reports, among the tests performed, M3DT as the best
phenotypic method for AmpC confirmation, as it is not only the most sensitive but
also specific test for AmpC as it rules out the resistance due to other
mechanisms like the porin channel.
PMID- 25120978
TI - Clinico-Immunological Profile of Children Infected with HIV Through Vertical
Transmission, in Southern India.
AB - BACKGROUND: Karnataka, being "High Prevalent State" of southern India, the HIV
infection among antenatal women has crossed 1%. There are very few reports
available with CD4 count and stage wise clinical spectrum among children. The
clinical spectrum among HIV infected infants and children vary in different areas
of the world. Hence it is important to know the spectrum of opportunistic
infections and their respective CD4 count among HIV infected children of our
locality. MATERIALS AND METHODS: The opportunistic infections among 31 paediatric
seropositive patients were evaluated. These all patients were classified as per
CDC guide lines into stage I, stage II, and stage III based on CD4 counts of >
1000cells/MUl, 500-999 cells/MUl,<500cells/MUl respectively. The opportunistic
infections were diagnosed by standard laboratory investigations. Clinical
spectrum presented by each stage children was documented. RESULTS: Children in
stage I were 5(16.1%),stage II 14(45.1%) and stage III 12(38.7%). Oral
candidiasis (29%) was the commonest, followed by recurrent respiratory tract
infection (25.8%), tubercular lymphadenitis (16.1%) and chronic diarrhoea
(12.9%). CONCLUSION: The present study showed the children with higher CD4 count
had few infections and children with lower CD4 count presented with multiple
opportunistic infections. This study also showed vertical transmission as the
sole mode of transmission.
PMID- 25120979
TI - Non-Invasive Diagnosis of Helicobacter pylori: Evaluation of Two Enzyme
Immunoassays, Testing Serum IgG and IgA Response in the Anand District of Central
Gujarat,India.
AB - CONTEXT: Validation of an accurate and less cumbersome noninvasive method to
detect current Helicobacter pylori infection is a requisite for any laboratory.
OBJECTIVES: The purpose of this study is to corroborate the usefulness of two
commercially available kits NovaTec ELISA-A and ELISA-G, in the detection of
ongoing H.pylori infection. MATERIALS AND METHODS: Two hundred and twenty eight
consecutive serum samples of symptomatic patients who attended the endoscopy unit
of "Deep" surgical hospital, Anand, which were collected during the period from
27th February 2008 to 31st august 2011, were studied. The sera were processed and
tested for the detection of the H.pylori IgG and IgA antibody by using a solid
phase; capture micro well ELISA, procured from Nova Tec immunodiagnostica GmbH
Germany. RESULTS: IgG ELISA showed 100% sensitivity and Negative predictive value
(NPV), while IgA ELISA was better in terms of specificity (61.4%) and accuracy
(63%) as compared to IgG ELISA. We found 7% (16/228) of IgA positive cases with
IgG negative response. IgG response was more common in reflux esophagitis
patients (OR 1.451, 95%CI-0.850-2.477) and then in gastritis (OR 0.962, 95%CI
0.570-1.621) and duodenitis(OR-0.806, 95%CI-0.112-5.827), while IgA positive
response was more common in duodenitis patients (OR-1.383, 95%CI-0.191-9.995) and
reflux esophagitis patients (OR 1.289, 95% CI-0.756-2.197) and least in duodenal
ulcer patients (OR 0.670, 95%CI-0.222-2.029). CONCLUSION: IgG update is reliable
and accurate test and can be expedient as a screening test and thus serve as an
alternative to endoscopy. For the purpose of excluding infection with H.pylori,
the performance of IgG is moderate (low specificity) but can be improved by
conjunctional IgA testing which will offer some additional diagnostic value.
PMID- 25120980
TI - Plasmid Profile Analysis and bla VIM Gene Detection of Metalo beta-lactamase
(MBL) Producing Pseudomonas aeruginosa Isolates from Clinical Samples.
AB - INTRODUCTION: Pseudomonas aeruginosa is a frequent colonizer of hospitalized
patients. They are responsible for serious infections such as meningitis,
urological infections, septicemia and pneumonia. Carbapenem resistance of
Pseudomonas aeruginosa is currently increasingly reported which is often mediated
by production of metallo-beta-lactamase (MBL). Multidrug resistant Pseudomonas
aeruginosa isolates may involve reduced cell wall permeability, production of
chromosomal and plasmid mediated beta lactamases, aminoglycosides modifying
enzymes and an active multidrug efflux mechanism. OBJECTIVE: This study is aimed
to detect the presence and the nature of plasmids among metallo-beta-lactamase
producing Pseudomonas aeruginosa isolates. Also to detect the presence of bla VIM
gene from these isolates. MATERIALS AND METHODS: Clinical isolates of Pseudomonas
aeruginosa showing the metalo-beta-lactamase enzyme (MBL) production were
isolated. The MBL production was confirmed by three different methods. From the
MBL producing isolates plasmid extraction was done by alkaline lysis method.
Plasmid positive isolates were subjected for blaVIM gene detection by PCR method.
RESULTS: Two thousand seventy six clinical samples yielded 316 (15.22%)
Pseudomonas aeruginosa isolates, out of which 141 (44.62%) were multidrug
resistant. Among them 25 (17.73%) were metallo-beta-lactamase enzyme producers.
Plasmids were extracted from 18 out of 25 isolates tested. Five out of 18
isolates were positive for the blaVIM gene detection by the PCR amplification.
CONCLUSION: The MBL producers were susceptible to polymyxin /colistin with MIC
ranging from 0.5 - 2MUg/ml. Molecular detection of specific genes bla VIM were
positive among the carbapenem resistant isolates.
PMID- 25120981
TI - Waging war against extended spectrum Beta lactamase and metallobetalactamase
producing pathogens- novel adjuvant antimicrobial agent cse1034- an extended
hope.
AB - Preamble: In the visage of multidrug resistance among gram negative bacilli, we
look forward to carbapenem group of drugs as empiric choice in seriously ill
patients. However increasing resistance to carbapenems, the last resort, is of
growing concern for all. It's high time to look beyond Carbapenems and emphasize
on Carbapenem sparers. OBJECTIVE: This study is to find the susceptibility
pattern of the novel adjuvant antimicrobial CSE 1034 a combination of
Ceftriaxone+sulbactam+disodium edetate for the current ESBL and MBL isolates in a
tertiary care centre. MATERIALS AND METHODS: A total of 823 gram negative
bacterial isolates were obtained from different clinical specimens during the
period of March, 2013 to October, 2013. The overall prevalence of
metallobetalactamase producing gram negative organisms was 11 percent (n=91). We
included a total of 141 clinical isolates for this study. RESULTS: Among 141
clinical isolates, 50 isolates (35%) were ESBL producers and 91 (65%) were MBL
producers. Maximum numbers of ESBL producers were identified in Escherichia coli
followed by Klebsiella pneumoniae, Acinetobacter baumannii and Proteus spp.
Maximum numbers of MBL producers were identified in Klebsiella pneumoniae
followed by Pseudomonas aeruginosa. CSE 1034 (Ceftriaxone+sulbactam+disodium
edetate) showed fairly good in-vitro susceptibility for these ESBL and MBL
producing isolates. It exhibited 64 % to 100% susceptibility and 18% to 22%
intermediate sensitivity to ESBL producing isolates and 42 % to 89 % susceptible
and 10 % to 51 % intermediate response to MBL producing isolates. CONCLUSION:
With increasing resistance to the commonly prescribed drugs used to treat
infections caused by variety of gram negative organisms,
Ceftriaxone+sulbactam+disodium edetate, a novel Antibiotic Adjuvant Entity (AAE)
may be a promising option.
PMID- 25120983
TI - Acanthamoeba detection in the anterior chamber after therapeutic penetrating
keratoplasty.
AB - Acanthamoeba infection has been recognized in almost all parts of the world. With
most of the literature focusing on contact lens related Acanthamoeba keratitis,
ophthalmologists may hesitate to diagnose this entity in patients without lenses.
We report the case of a patient with Acanthamoeba infection of the anterior
chamber, unrelated to contact lens wear, diagnosed by examination of aqueous tap
following penetrating therapeutic keratoplasty.
PMID- 25120982
TI - Isolation of MRSA, ESBL and AmpC - beta -lactamases from Neonatal Sepsis at a
Tertiary Care Hospital.
AB - BACKGROUND AND OBJECTIVES: The emergence of methicillin resistant Staphylococcus
aureus (MRSA) and extended spectrum beta-lactamases (ESBLs) in neonatal intensive
care unit patients is increasing. This study aims to find out the bacteriological
profile in neonatal sepsis and study their antimicrobial susceptibility pattern
including detection of MRSA and ESBLs. MATERIALS AND METHODS: This study was
conducted for a period of one and a half years from January 2010 to June 2011 in
a tertiary care hospital in Chennai. A total of 182 blood samples were collected
using sterile precautions. They were processed following standard laboratory
protocol. Antibiogram was done using appropriate antibiotics by Kirby-Bauer disc
diffusion method. Isolated Staphylococcus aureus were tested for methicillin
resistance using Cefoxitin disc (30MUg), ESBL was detected using combined disc
method, MIC reduction and Polymerase chain reaction, metallobetalactamases using
EDTA and Amp-C beta lactamases using AmpC disc test. C-reactive protein (CRP) was
estimated for all the cases. RESULTS: Out of the 182 cases, 110 (60.4%) were
culture positive. Fifty five (63.9 %) of early onset sepsis cases had Gram
negative bacteria (GNB) and 19 (79.1%) of late onset sepsis cases had Gram
positive bacteria. Out of the total pathogens, 31 (28.1%) were Klebsiella
pneumoniae and 30 (27%) were Staphylococcus aureus. 17 (56.6 %) of Staphylococcus
aureus were found to be MRSA and they were 100% sensitive to Vancomycin. 33
(67.3%) of Enterobacteriaceae were ESBL producers. ESBL isolates were 100%
sensitive to Imipenem. Three (6.1%) of Enterobacteriaceae were AmpC producers and
3 (27.2%) of Pseudomonas aeruginosa were MBL producers. CRP was positive in 99
(54.3%) cases, out of which 94 (94.9%) were culture positive. CONCLUSION:
Klebsiella spp. and Staphylococcus aureus were the commonest bacteria causing
neonatal sepsis in this centre. Multidrug resistance among the isolates was
common. Early diagnosis and institution of specific antibiotics after studying
the sensitivity pattern will help in reducing neonatal morbidity and mortality
and prevent emergence of drug resistant strains.
PMID- 25120986
TI - Seroprevalence of Hepatitis B, Hepatitis C and Human Immunodeficiency viruses
amongst Injecting Drug Users in Mumbai,India.
PMID- 25120984
TI - Multidrug resistant Shigella flexneri : a rare case of septicemia in an infant.
AB - Shigellosis is still an important public health problem in developing and under
developed countries. It may lead to rare but potentially fatal various extra
intestinal complications like septicemia, involvement of CNS, urinary tract and
liver especially in young malnourished children. The disease is difficult to
prevent as only few bacteria are required for causing infection and there is
increasing infection with multi drug resistant strains. A 6-month-old infant
developed septicemia caused by multi drug resistant Shigella flexneri during an
episode of gastrointestinal infection. The patient was managed in the emergency
ward but unfortunately the infant expired. Considering septic shock, blood
culture, stool culture and other relevant investigations were done. Stool as well
as blood culture yielded Shigella flexneri. The isolates were multidrug
resistant. Following is a rare case presentation of Shigella septicemia with
severe shock, DIC and convulsions. The case report demonstrates how shigellosis
can lead to a rare life threatening complication and hence should be considered
as a possibility in septicemia associated with diarrhea and vomiting in infant
and young children.
PMID- 25120985
TI - Non-pigmented strain of serratia marcescens: an unusual pathogen causing
pulmonary infection in a patient with malignancy.
AB - Serratia marcescens is a member of the family Enterobacteriaceae. It has emerged
in recent years as an opportunistic pathogen of nosocomial infections. Some
biotypes of Serratia marcescens produce the non-diffusible red pigment
prodigiosin. Though both pigmented and non-pigmented biotypes may be pathogenic
for humans, the non-pigmented biotypes are more virulent due to cytotoxin
production and presence of plasmids mediating antibiotic resistance. However in
India only one study done 31 years back has reported on infections caused by non
pigmented strains of Serratia marcescens. We present a case of a patient with
squamous cell carcinoma of the left retromolar trigone, soft palate and buccal
mucosa, who developed pulmonary infection with non-pigmented strain of Serratia
marcescens. According to the available literature, this is the second report on
infection with non-pigmented strain of Serratia marcescens from India. It is
imperative to accurately detect the non-pigmented biotypes due to their tendency
to cause serious and difficult to treat infections.
PMID- 25120987
TI - Red Cell Distribution Width and Serum BNP Level Correlation in Diabetic Patients
with Cardiac Failure: A Cross - Sectional Study.
AB - INTRODUCTION: Red cell distribution width (RDW) is a red cell measurement given
by fully automated hematology analyzers. It is a measure of heterogeneity in the
size of circulating erythrocytes. Studies have shown that it is a prognostic
marker in non - anemic diabetic patients with symptomatic cardiovascular disease
but its correlation with cardiac failure in diabetics has not been studied so
far. Moreover, studies have also shown that a higher RDW may reflect an
underlying inflammatory state. Since Diabetes is a pro inflammatory state there
is a possibility that it might have an influence on the RDW values even when
there is no cardiac failure, but research data on this aspect is lacking. B-type
natriuretic peptide (BNP) is a proven marker for cardiac failure whose values are
comparable with echo cardio graphic findings in assessing the left ventricular
dysfunction. AIM AND OBJECTIVES: This study aimed to find out the correlation
between RDW% and serum BNP levels in Diabetics with heart failure (cases) when
compared to those without failure (controls). Further, we compared the RDW %
values of the cases with controls. Settings and Design : The study was approved
by institutional ethical and research committee. A cross-sectional study was
conducted with patients attending the Diabetes clinic of a tertiary care hospital
in Chennai, India, during the period of October to December 2013. Hundred known
cases of type II Diabetes mellitus attending Diabetes centre of the Hospital,
with clinical and Echo cardio graphic features of cardiac failure were included
as cases. Hundred age and gender matched diabetics with negative history of
cardiovascular disease and with normal Echo cardio graphic features were included
as controls. Informed consent was obtained from all the cases and controls.
Demographic data and clinical history were gathered from all the cases and
controls by using a standardized self - administered questionnaire. Biochemical
and hematological parameters which included Fasting and Postprandial blood sugar,
Glycosylated hemoglobin, Complete Blood count including RDW and serum BNP were
performed for all the cases and controls. STATISTICAL ANALYSIS: RESULTS were
tabulated and analysed using SPSS 20.0 version RESULTS: A statistically
significant correlation (p<.001) was found between Red cell Distribution Width %
and Serum B type Natriuretic Peptide values in the cases. Further, RDW% showed a
statistically significant difference between cases and controls. CONCLUSION: RDW%
can be used as a screening parameter to identify cardiac failure in Diabetic
patients similar to non-diabetic cardiac failure. RDW% values are significantly
higher in cases of Diabetes with failure in comparison to uncomplicated Diabetes.
PMID- 25120989
TI - Incidental detection microfilaria in subcutaneous breast nodule of lactating
female fnac: a rare case report.
AB - Filariasis is a major public health problem which is faced in tropical countries
like India. Its diagnosis is made by using peripheral blood smears. However,
microfilaria has been detected incidentally during FNACs of various lesions,
which were done in clinically unsuspected cases. We are reporting here, an
uncommon case of filariasis, which caused a nodular, subcutaneous swelling in
left breast of a 30 year old lactating female. A nodular subcutaneous swelling
can be caused in breast of a lactating female by lactational associated mastitis,
but filaria causing a nodular swelling in a lactating breast is a rare
presentation. Aspiration of the swelling demonstrated enormous pathogen presence
caused by Woucheria bancrofti and the patient responded well to six weeks of
daily anti-filarial treatment with diethylcarbamazine citrate.
PMID- 25120990
TI - Myxoid leiomyosarcoma of ovary-a rare case report.
AB - Primary pure myxoid leiomyosarcoma of the ovary is extremely rare, comprising of
only 1% of the ovarian tumours. Patient presented with a mass in the right iliac
fossa since three months. Radiological diagnosis of broad ligament fibroid was
given. Right salphingo-oophorectomy with enucleation of ischial fossa and wedge
biopsy of left ovary was carried out. Based on gross, microscopy and
immunohistochemistry a diagnosis of primary myxoid leiomyosarcoma of ovary was
made. We report a rare case of primary pure myxoid leiomyosarcoma of the ovary
with metastasis to ischial fossa emphasising on reliable prognostic markers.
Ovarian leiomyosarcomas are highly aggressive tumours with poor prognosis.
PMID- 25120988
TI - Rare case of chest wall schwannoma with destruction of rib, masquerading as a
breast mass.
AB - Schwannomas are slow growing, benign, nerve sheath tumours of Schwann cell
origin. They predominantly involve head, neck and flexor surfaces of upper and
lower extremities, while the chest wall is an uncommon location for schwannomas.
Schwannomas may rarely cause erosion of adjacent bone. We are reporting a very
rare case of a chest wall schwannoma with destruction of rib which occurred in a
35-year-old female patient, which initially presented as a breast mass and was
radiologically misinterpreted as a malignant soft tissue tumour.
PMID- 25120991
TI - Chondrolipoma of the lower lip: a case report.
AB - A chondrolipoma is an extremely rare form of a benign mesenchymal tumour which
contains mature fatty tissue and cartilage. We are presenting a case of
chondrolipoma of the lower lip which was seen in a 6-year-old girl.
Chondrolipomas are rare neoplasms; their terminologies and pathogeneses have been
controversial in the past. Chondrolipomas are uncommonly seen in the oral cavity,
in children and in females. Hence, we are reporting this present case because
rarity of this lesion.
PMID- 25120992
TI - Clear cell atypical fibroxantoma: a rare variant of atypical fibroxanthoma and
review of the literature.
AB - Atypical fibroxanthoma (AFX) is a superficial variant of pleomorphic malignant
fibrous histiocytoma. Clear cell atypical fibroxanthoma (CCAFXA) is a rare
variant of atypical fibroxanthoma. A 74-year-old male patient presented with a
rapidly growing nodule on the shoulder, which had appeared over a 5-months
period. Lesion was excised by the plastic surgeon. Microscopic examination showed
an ulcerated nodule composed of pleomorphic spindled and polygonal cells with
clear or vacuolated cytoplasm. The neoplastic cells were stained positively with
CD68 and CD10 and were stained negative with S-100, Melan A, muscle-specific
actin, or pan-cytokeratin. Final diagnosis was clear cell atypical fibroxanthoma.
CCAFXA should be differentiated from other clear-cell neoplasms of the skin. Best
of our knowledge only 11 cases CCAFXA of have been reported in published studies
till date. Herein, we reported 12th case in literature of CCAFXA and review of
the literature.
PMID- 25120993
TI - Primary ovarian mucinous carcinoma with signet ring cells - report of a rare
case.
AB - Presence of signet ring cells in ovarian neoplasms are commonly encountered in
Krukenberg tumours of ovary. Unusual presence in primary ovarian mucinous tumours
may create a diagnostic difficulty. To the best of our knowledge only very few
such cases have been reported in the literature indicating their rarity. We
report a case of primary ovarian mucinous carcinoma with signet ring cells. The
purpose of this presentation is to sensitize the pathologists to consider primary
mucinous carcinoma as a differential diagnosis in tumours with signet ring cells.
PMID- 25120994
TI - Gastrointestinal stromal tumour of small intestine presenting as a mesenteric
mass.
AB - Gastrointestinal stromal tumors (GISTs) are uncommon tumors; accounts for 0.1% to
3% of all gastrointestinal neoplasm. Most common site of involvement is stomach
(60-70 %), small intestine (20-30 %) and rarely at extra-gastrointestinal sites
like omentum and mesentery called as extra-gastrointestinal stromal tumor
(EGIST). Diagnosis is based on characteristic histological findings and
expression of transmembrane receptor tyrosine kinase protein (CD 117) derived
from activated c-kit gene. Herein, we report a case of GIST of small intestine
presented as mesenteric mass in a 35- year-old female and discuss review of
literature.
PMID- 25120995
TI - Chordoma Cutis - A Diagnosis not to be Missed.
AB - Chordomas are rare midline tumors of the bone usually arising from sacrum, skull
bones and spine, close to neuraxis. However an extensive involvement of the soft
tissues can simulate a soft tissue subcutaneous tumour of the gluteal region -a
presentation called chordoma cutis. Our patient presented with a gluteal mass and
a trucut biopsy was done suspecting a soft tissue tumour. The hematoxylin and
eosin stained section of the biopsy closely simulated a lipomatous tumour.
However, on closer inspection the clear cells were found to have very fine
vacuolations.The usual myxoid background and characteristic physaliferous cells
seen in chordomas were not seen. Still a differential of chordoma was entertained
in view of the site and age of the patient. Immunohistochemistry for cytokeratin
and S-100 was performed and both were unambiguously positive. On literature
search, we came across a soft tissue tumour called parachordoma which mimics
chordoma both morphologically and immunohistochemically and has also been
reported in the gluteal region. An MRI was performed which showed the tumour to
be arising from the sacrum and secondarily involving the gluteal soft tissues.
This case highlights the importance of considering chordoma in the differential
diagnosis of gluteal masses with clear cell morphology even in the absence of
physaliferous cells and myxoid background before signing them out as lipomatous
tumours.
PMID- 25120996
TI - A rare presentation of gallbladder carcinoma metastasis.
AB - Gallbladder carcinoma is the 5th most common gastrointestinal cancer. Gallbladder
cancer preferentially metastasizes to regional lymph nodes and liver parenchyma.
Bone metastases from gallbladder carcinoma are rare presentation. We report a
case of gallbladder carcinoma with solitary metastasis to femur bone with
surrounding soft tissue involvement, mimicking as soft tissue tumour involving
bone.
PMID- 25120997
TI - Comparative efficacy of two different dosages of intrathecal magnesium sulphate
supplementation in subarachnoid block.
AB - BACKGROUND: Spinal anaesthesia is the primary anaesthetic technique for many
types of surgeries. Adjuncts to the local anaesthetics (LA) used in spinal
anaesthesia can exhibit undesirable side-effects like respiratory depression,
urinary retention, pruritis, haemodynamic instability and nausea and vomiting,
limiting their use. Magnesium when used in therapeutic doses avoids all of these
side-effects. MATERIALS AND METHODS: We conducted a randomized double blind study
on 90 patients, 30 in each group, scheduled for orthopaedic lower limb surgery
under subarachnoid block. Group I: received bupivacaine (0.5%), 12.5 mg + 0.5 ml
of preservative free 0.9% normal saline, Group II received bupivacaine (0.5%),
12.5 mg + 0.2 ml (50 mg) of preservative free 25 % magnesium sulphate + 0.3 ml of
preservative free 0.9% normal saline Group III: received bupivacaine (0.5%) 12.5
mg + 0.3 ml (75 mg) of 25 % magnesium sulphate + 0.2 ml of preservative free 0.9%
normal saline for subarachnoid block. The onset and duration of sensory block,
the highest dermatomal level of sensory block, motor block, time to complete
motor block recovery and duration of spinal anaesthesia were recorded.
STATISTICAL ANALYSIS: ANOVA was applied to determine the significance of
difference between different groups. If p-value was significant then Turkey's
Post Hoc Multicomparison test was applied. Values of p<0.05 were considered to be
statistically significant. RESULTS: The time of maximum sensory block, time of
onset of motor block, duration of sensory block, duration of motor block and time
of analgesia request were prolonged in patients given magnesium 50mg and 75mg
along with local anaesthetic intrathecally. CONCLUSION: N-methyl-D-aspartate
(NMDA) receptor antagonist, magnesium when administered intrathecally along with
local anaesthetics prolongs the duration of spinal analgesia without adverse
effects.
PMID- 25120999
TI - Antidepressant effect of ketamine in sub anaesthetic doses in male albino mice.
AB - BACKGROUND: Depression is the most common mental disorder in community settings,
and is a major cause of disability across the world. Antidepressants such as SSRI
(Selective Serotonin Reuptake Inhibitor) and TCA (Tricyclic antidepressants) are
used. These drugs affect the adrenergic and serotonergic pathways. These drugs
have an unfavorable side effect profile, take longer time to act and are not very
effective in resistant cases. Alternate pathways involving the glutamate
receptors have also been linked with depression, hence Ketamine an NMDA
antagonist was evaluated for the antidepressant effect. AIM: To study the
antidepressant effect of ketamine in subanaesthetic doses in male albino mice.
STUDY DESIGN, MATERIALS AND METHODS: The study was a randomized controlled animal
study done on 30 male albino BALB/c mice divided into five groups with Imipramine
(10mg/kg) as the standard drug and Ketamine in varying doses (5, 7.5, 10 mg/kg)
as the test drug. The animal model used was the forced swim test. The reduction
in immobility time was taken as the index of the antidepressant effect.
STATISTICAL ANALYSIS: The data were analysed with the one way ANOVA test using
SPSS version 12. RESULTS AND CONCLUSION: The data analysis showed that Ketamine
at a dose lower dose of Ketamine (5mg/kg) did not show a significant
antidepressant effect in contrast to the higher doses (7.5 and 10mg/kg) which
showed significant antidepressant effect ('p' > 0.05). The inference of this
study is that Ketamine has significant antidepressant property at variable dose
ranges and further studies can be done on these lines.
PMID- 25120998
TI - Beneficial effects of nebivolol in comparison with atenolol on safety and
tolerability in essential hypertension.
AB - INTRODUCTION: Hypertension, "The silent killer" is a multifactorial disorder
which is asymptomatic and if left untreated leads to lethal complications.
Nebivolol is a third generation beta blocker with additional vasodilating
property due to nitric oxide release. AIM: The current study aims to assess
efficacy and safety of Nebivolol and compare with Atenolol. METHODS: This was
prospective, double blind, comparative controlled clinical study. Total 90
patients were enrolled into study as per selection criteria. Patients were
randomized to receive Atenolol and Nebivolol with 45 patients in each group for
12 weeks. RESULTS AND CONCLUSION: The mean reduction diastolic blood pressure in
Nebivolol and Atenolol group was 10.77+/-2.60 and 10.05+/-2.83 respectively. The
number of patients with adverse effect events was higher in the Atenolol than in
the Nebivolol group (36.84% of Atenolol Vs 12.82% of Nebivolol). Thus it can be
concluded that, for the same antihypertensive effect, Nebivolol was better
tolerated than Atenolol.
PMID- 25121000
TI - Comparative study of high dose mono-therapy of amlodipine or telmisartan, and
their low dose combination in mild to moderate hypertension.
AB - INTRODUCTION: Hypertension is one of the major public health challenges
worldwide. Angiotensin receptor blockers (ARBs) and Calcium channel blockers
(CCBs) are among the first line antihypertensive drugs. However, optimal
treatment strategies in mild to moderate hypertensives who failed to achieve
blood pressure (BP) control with low-dose mono-therapy are not well established.
This study was done to compare efficacy and safety of high dose mono-therapy of
Amlodipine, Telmisartan and their low dose combination in mild to moderate
hypertensives who failed to achieve BP control with low dose mono-therapy of
either drug. MATERIALS AND METHODS: A total of 96 patients, fulfilling inclusion
and exclusion criteria were enrolled in the study after obtaining informed
consent. Patients were randomized into three treatment groups i.e. Telmisartan 80
mg, Amlodipine 10 mg and low dose combination of Telmisartan 40 mg +Amlodipine 5
mg once daily for two months. The systolic BP, Diastolic BP, and ADRs were
recorded at 0, 2, 4, 8 weeks. RESULTS: In the present study, significant
reduction of mean systolic blood pressure (SBP) and mean diastolic blood pressure
(DBP) was seen in all the three treatment groups. Low dose combination of
Amlodipine 5 mg and Telmisartan 40 mg showed statistically significant reduction
in SBP as compared to Telmisartan 80 mg mono-therapy and in DBP as compared to
Amlodipine 10 mg mono-therapy. Maximum adverse drug reactions (ADRs) were
reported in Amlodipine mono-therapy group, like ankle oedema, constipation,
headache and fatigue. DISCUSSION AND CONCLUSION: In term of BP control, low-dose
combination therapy appears a better therapeutic approach than high-dose mono
therapy.
PMID- 25121001
TI - Comparative Study of Lithotripsy and PCNL for 11-15 mm Lower Caliceal Calculi In
Community Health Hospital.
AB - BACKGROUND AND PURPOSE: Percutaneous Nephrolithotomy (PCNL) is not a popular
procedure in smaller sized calculi due to its invasive nature, complications and
need for anesthesia. Small sized lower caliceal calculi are generally treated by
ESWL but have significantly less clearance rate in spite of several sittings.
Here we want to study the efficacy and safe of both procedures in 11 to 15 mm
lower caliceal calculi. MATERIALS AND METHODS: We present comparative study of
lithotripsy and PCNL in 11-15 mm lower caliceal calculi in our hospital. Total
156 patients were studied 78 underwent lithotripsy and 78 underwent PCNL. We
compared results in the form of clearance rate, the number of settings needed,
hospital stay, need for anesthesia, blood transfusion rate, chest complication,
the incidence of sepsis, the need for another procedure, need for stenting in
either group. RESULTS: We found a 67.95% clearance rate in SWL group and 97.43%
clearance rate in PCNL group. Hospital stay was minimum in SWL group and was 46
hours in PCNL group. The procedure time was 42 minutes in PCNL and it was 114
mins in SWL (considering all settings). The rest of the complications like chest
complication, sepsis and bleeding were negligible due to the small size of
calculi. CONCLUSION: In a small sized LPC calculi, PCNL is gaining increased
popularity due to lower complication and high safety and complete clearance rate.
It is wide accepted by society as the patient is totally stone free at the end of
the procedure. SWL is less invasive but less effective and has given significant
discomfort to patients.
PMID- 25121002
TI - Evaluation of the Hepato and Nephron-Protective Effect of a Polyherbal Mixture
using Wistar Albino Rats.
AB - AIM: A polyherbal formulation prepared from a mixture of leaves of Gongronema
latifolia, Ocimum gratissimum and Vernonia amygdalina (GOV) was evaluated for
hepato-nephro protective properties against acetaminophen-induced toxicity in
Wistar albino rats. MATERIALS AND METHODS: Normal Wistar albino rats were orally
treated with different doses of GOV extract (2, 4 and 8 g/kg b. wt), distilled
water and some standard hepatoprotective drugs such as Liv 52 and silymarin for
14 days. However, a day prior to the 14th day, 3 g/kg body weight dose of
Acetaminophen (APAP) was administered p.o. 1h before GOV and the standard drugs
to induce hepatic and renal damage. The normal control was setup which received
only distilled water. The serum levels of liver marker enzymes, biochemical
analytes, antioxidant enzymes and hematological parameters were monitored.
RESULTS: The results showed that pretreatment of experimental animals with a
different doses of the polyherbal formulation dose dependently caused a
significant (p<=0.05) increase in the levels of most of the measured
hematological parameters but significantly (p<=0.05) reduced the levels of MCV
and monocytes when compared to the APAP induced toxin control group. Rats
pretreated with GOV exhibited significant (p < 0.05) increase in serum levels of
ALP, ALT, AST, GGT, LDH, Cholesterol, Triglycerides, Urea and a subsequent
decrease in Albumin, Creatine and Total protein when compared to the normal rats.
This trend in enzyme and biochemical analytes levels were significantly (p <
0.05) reversed when compared to toxin control group. GOV significantly (p < 0.05)
and dose dependently increased the serum, kidney and hepatic CAT, GPx, GSH, GST,
SOD and total protein activity in APAP induced damage in rats compared to the
toxin control groups. CONCLUSION: The data from this study suggest that the
polyherbal formulation possess hepato and nephron-protective potential against
acetaminophen induced hepatotoxicity in rats, thus providing scientific rationale
for its use in traditional medicine for the treatment of liver diseases.
PMID- 25121003
TI - Pharmacotherapy of Bipolar Affective Disorder: A Hospital based Study from Sub
Himalayan Valley of Nepal.
AB - INTRODUCTION: In Bipolar disorder the mood of the patients fluctuates between
depression and mania. The main objective of the study was to find out the
commonest mood stabilizers used for the treatment of Bipolar affective disorders
in Western Nepal in hospitalized patients in an actual clinical set up. METHODS:
This was a cross-sectional study which was conducted between October 2009 and
September 2010 at Psychiatric ward at Manipal teaching hospital, Pokhara, Nepal,
a tertiary care hospital situated in Western Nepal. The diagnosis of the disease
was based on ICD-10 (Tenth revision) Classification of mental and Behavioural
disorders, Diagnostic Criteria for Research. We calculated odds ratio and their
95% confidence intervals (95% CI). p< 0.05 was considered as statistically
significant. RESULTS: 62.1% of the patients were less than 40 yrs, 56.3% were
male, 72.4% were unemployed and 75.9% of the patients were having monthly income
<10,000/month. As far as ethnicity is concerned 37.9% of the cases were Brahmin
and by occupation 29.9% of the patients were students followed by housewife
25.3%, labour 17.2%, retired 13.8% respectively. Drugs and Psychotherapy [OR 1.4,
95% (CI 0.575, 3.4017)] was prescribed in age <40 years as compared to age>40
yrs. Male patients [OR 7.22, 95% (CI 0.862, 60.499)] and [OR 2.353, 95% (CI
0.857, 6.455)] received drugs by trade names and drugs not from the national drug
list of Nepal as compared to females. Monthly income <10,000/month and [OR 2.8,
95% (CI 0.742, 10.56)] tendency of receiving drugs by trade names. Among the mood
elevators Sodium valproate was the commonest drug to be prescribed in
51/87(58.6%) patients followed by Lithium in 30/87 (34.5%) cases and
Carbamazepine in 6/87 (6.9%) cases. Sodium valproate was prescribed at 1,000
mg/day, Lithium was prescribed at 900 mg/day in and Carbamazepine was prescribed
at 800 mg/day. CONCLUSION: Among all the mood elevators Sodium valproate is the
commonest drug prescribed for the treatment of bipolar affective disorder,
recommended that there is a trend of using newer drugs like sodium valproate
rather than the conventional mood stabilizers like Lithium for bipolar affective
disorder in Western Development region of Nepal.
PMID- 25121004
TI - Garenoxacin in Skin and Skin Structure Infections Sustained due to Road Traffic
Accident.
AB - Skin and soft tissue infections represent a continuum of symptoms that range from
uncomplicated cellulitis to the potentially lethal entity necrotizing fasciitis
that is often considered to be microbial invasions of the epidermis, dermis and
subcutaneous tissues. Garenoxacin, a newer oral des-fluoroquinolone having potent
antimicrobial activity against wide variety of common pathogens involved in skin
and skin structure infections (SSTIs), including the resistant strains offer the
advantage of broad spectrum of coverage including gram positive, gram negative
and anaerobic organisms. This case study indicates the utility of garenoxacin in
treating skin and soft tissue infections caused by road traffic accidents.
PMID- 25121005
TI - A Population based Study on Alcoholism among Adult Males in a Rural Area, Tamil
Nadu, India.
AB - BACKGROUND: India's reputation as a country with a culture of abstinence
especially in matters regarding alcohol is underserved. There has been a rapid
proliferation of city bars and nightclubs in recent years and people are fast
shedding its inhibitions about alcohol as a lifestyle choice. This scenario has
led to fears of an undocumented rise in alcohol abuse among all sections of
society. Policies by the government has been laid down to regulate sales and
pricing of alcohol, but not well improvised. Our aim was to find out the
prevalence of alcoholism among adult males in a rural population and also to
analyze its association between various factors. MATERIALS AND METHODS: A cross
sectional study in a rural population at Kuthampakkam village, in Poonamallee
block of Tiruvallur district in Tamil Nadu, India. The study population included
adult male population. Simple random sampling method was adopted. A structured
questionnaire was used to collect information regarding the background
characteristics, history of alcoholism and certain social factors. STATISTICAL
ANALYSIS: Data entry and analysis was done using Statistical Package for Social
Sciences (SPSS) version 15 software. Descriptive statistics were calculated for
background variables and the prevalence of the alcoholism. Chi-square test and p
value were calculated to see the association between alcoholism and social
factors. RESULTS: A total of 157 adult male were enrolled in the study. The mean
age of the study participants was 37.20 years. The prevalence of alcoholism among
the study participants was 35.7%. Among them only 4.5% who presented with
symptoms of chronic alcoholism had taken treatment. Reasons for not taking
treatment for alcoholism among study population were mainly due to their family
problems (55.2%). CONCLUSION: Although alcohol consumption has existed for many
centuries, the quantity, usage pattern, and resultant problems have undergone
substantial changes over the past 20 years. These developments have raised
concerns about the public health and social consequences. Awareness among the
population and necessary rehabilitation and self-help programs will help in
bringing down the prevalence of alcoholism.
PMID- 25121006
TI - Stressing 'mental stress' in hypertension: a rural background study.
AB - BACKGROUND: Modern life is full of hassles, deadlines, frustrations and demands.
Mental stress or psychosocial stress is one of the major risk factor for
hypertension which itself is the risk factor for various other cardiovascular
diseases. OBJECTIVES: To find out the prevalence of hypertension among rural
study population above 40 years of age and analyze the relationship between
mental stress and Hypertension amongst them. METHODOLOGY: A cross-sectional
descriptive study was undertaken in rural Maharashtra from January 2007 till
December 2008. Systematic random sampling was done to cover 3600 sample size
above 40 years of age. A protocol was devised containing requisite items of socio
demographic data and data was collected from individual households with the help
of ancillary staff. Mental stress score based on Presumptive stressful life event
score (PSLES) was used. For statistical analysis, Chi-square test, F-test and Z
test were used. RESULTS: Prevalence of hypertension was found to be 5.92%. Males
had maximum cases of hypertension [169 (7.27%)] compared to females [44 (3.44%)]
which was statistically significant (chi2 = 21.63, p < 0.001). The rise in number
of cases with increasing age was observed. Significant number of cases [127
(7.68%, p= 0.00006)] were found in study population belonging to 'More stress'
group. Mean mental stress score of hypertensive study subjects was significantly
higher (219) than normotensive study subjects (157). Males had significant higher
stress score in both hypertensive and Normotensive group. CONCLUSION: Total 213
cases of hypertension were detected (5.92%). As the stress increases, risk of
hypertension increases. Statistically significant association was found between
mental stress and hypertension for males. But in females, no such association was
found. Mental stress definitely acts as risk factor for hypertension. Invention,
propagation and practical application of various stress relieving measures &
exercises should be done.
PMID- 25121007
TI - Same dog bite and different outcome in two cases - case report.
AB - There is still no cure for rabies and survival from clinical rabies is extremely
rare. It is a preventable disease if the post exposure prophylaxis is initiated
in time and administered as per WHO guidelines including administration of rabies
immunoglobulin. The role of passive rabies immunization products is to provide
the immediate availability of neutralizing antibodies at the site of the exposure
before it is physiologically possible for the patient to begin producing his or
her own antibodies after vaccination. In this case report, the same dog has
bitten to a boy and to an adult. Local wound treatment and use of human rabies
immunoglobulin as well as gluteal region as a site of bite were the probable
reasons for survival of the boy. On the other hand no local wound treatment, no
use of rabies immunoglobulin and finger as a site of bite are the probable
reasons for death of an adult due to rabies.
PMID- 25121008
TI - Topical vs Combination Ciprofloxacin in the Management of Discharging Chronic
Suppurative Otitis Media.
AB - OBJECTIVES: To study the microbial flora and determine the efficacy of topical
ciprofloxacin ear drops in comparison with combination of topical and oral
ciprofloxacin as first line management in patients diagnosed with chronic
suppurative otitis media. MATERIALS AND METHODS: Prospective randomized
interventional clinical trial on 100 patients who presented with an acute episode
of CSOM to our outpatient department. RESULTS: In our study, topical
ciprofloxacin therapy was found to be an effective treatment for an acute on
chronic otitis media as was the combination therapy though the overall recurrence
rate was found to be more in the former group. CONCLUSION: In the absence of
systemic infection or serious underlying disease, topical antibiotics alone
constitute first line treatment for most patients with chronic suppurative otitis
media, finding no evidence that systemic antibiotics alone or in combination with
topical preparations improve treatment outcomes compared with topical antibiotics
alone.
PMID- 25121009
TI - Recurrent angiofibroma of ethmoid region - a rare variant.
AB - The common variant of angiofibromas of head and neck region is juvenile
nasopharyngeal angiofibroma (JNA). However extranasopharyngeal angiofibromas
(ENAF) occurs very rarely at any age in either sex, and they differ from
classical JNA in incidence, clinical and radiological presentation. They form the
differential diagnosis for any mass nose or nasal polyp. We present a case of
recurrent angiofibroma of ethmoid region presented with recurrent lesion with
bilateral proptosis and bossing of forehead. MRI showed involvement of bilateral
nasal cavities, ethmoids and frontal sinuses with erosions of ethmoid roof and
posterior table of frontal sinuses. Entire mass was excised by craniofacial
resection which was histopathologically confirmed as Angiofibroma.
PMID- 25121010
TI - Atrophic rhinitis presenting with ethmoidal mucocele: a case report.
AB - Atrophic rhinitis (AR) is a chronic debilitating nasal mucosal disease
predominantly prevalent in tropical countries. In the present case a 70-year-old
female presented with a swelling in the right medial canthal area for six months
and had features of Atrophic rhinitis with large septal perforation leading to
saddle nose deformity. Computed tomography pictures were suggestive of ethmoidal
mucocele and was later decompressed endoscopically. The sequelae and
complications of AR like nasal septal perforation, saddle nose deformity, chronic
rhinosinusitis (CRS), local and systemic spread of infection, atrophic
pharyngitis, laryngitis, dacryocystitis and nasal myiasis have been reported in
literature. To the best of our knowledge, this is the first reported case of AR
presenting with ethmoidal mucocele. A case of AR with CRS is to be treated with
caution as it can lead to complications as it is often neglected.
PMID- 25121011
TI - Evaluation of outcome of corrective ulnar osteotomy with bone grafting and
annular ligament reconstruction in neglected monteggia fracture dislocation in
children.
AB - INTRODUCTION: Neglected Monteggia fracture dislocation in the paediatric age
group constitutes significant disability in respect to pain, stiffness,
deformity, neurological compromise and restriction of activities of daily living.
MATERIALS AND METHODS: A longitudinal prospective study was done on 21 children
with old Monteggia fracture-dislocation which included 18 cases of Bado type I
and 3 cases of Bado type III at the department of orthopaedics, IPGME&R,SSKM
hospital, Kolkata, India between 2007 and 2012. All were treated by modified
Hirayama corrective osteotomy of ulna with wedge bone grafting along with
restoration of its length and reconstruction of annular ligament using Bell Tawse
method and fixation of radial head with transcapitellar Kirschner wire. Average
follow up period was 5.5 years. RESULTS AND ANALYSIS: Results were evaluated on
the basis of 100 point Mayo Elbow Performance Index, radiology and questionnaire.
The mean postoperative increase in Mayo Elbow Performance Index score was 30 with
average increase in the range of movement by 30o. In three cases, there was
subluxation of radial head and in addition one had transient palsy of posterior
interosseous nerve. Three cases showed distortion of the radial head which were
insignificant functionally. Results of improvement in mean MEPI were analysed by
chi-square test and was significant at 0 .01 level of significance. CONCLUSION:
Study showed good results with modified Hirayama osteotomy with annular ligament
reconstruction using Bell Tawse procedure which is a more biological option for
restoration of elbow biomechanics.
PMID- 25121012
TI - Vibration Therapy in Management of Delayed Onset Muscle Soreness (DOMS).
AB - Both athletic and nonathletic population when subjected to any unaccustomed or
unfamiliar exercise will experience pain 24-72 hours postexercise. This exercise
especially eccentric in nature caused primarily by muscle damage is known as
delayed-onset muscle soreness (DOMS). This damage is characterized by muscular
pain, decreased muscle force production, reduce range of motion and discomfort
experienced. DOMS is due to microscopic muscle fiber tears. The presence of DOMS
increases risk of injury. A reduced range of motion may lead to the incapability
to efficiently absorb the shock that affect physical activity. Alterations to
mechanical motion may increase strain placed on soft tissue structures. Reduced
force output may signal compensatory recruitment of muscles, thus leading to
unaccustomed stress on musculature. Differences in strength ratios may also cause
excessive strain on unaccustomed musculature. A range of interventions aimed at
decreasing symptoms of DOMS have been proposed. Although voluminous research has
been done in this regard, there is little consensus among the practitioners
regarding the most effective way of treating DOMS. Mechanical oscillatory motion
provided by vibration therapy. Vibration could represent an effective exercise
intervention for enhancing neuromuscular performance in athletes. Vibration has
shown effectiveness in flexibility and explosive power. Vibration can apply
either local area or whole body vibration. Vibration therapy improves muscular
strength, power development, kinesthetic awareness, decreased muscle sore,
increased range of motion, and increased blood flow under the skin. VT was
effective for reduction of DOMS and regaining full ROM. Application of whole body
vibration therapy in postexercise demonstrates less pressure pain threshold,
muscle soreness along with less reduction maximal isometric and isokinetic
voluntary strength and lower creatine kinase levels in the blood.
PMID- 25121013
TI - A Study of Etiological Pattern in an Epidemic of Acute Febrile Illness during
Monsoon in a Tertiary Health Care Institute of Uttarakhand, India.
AB - BACKGROUND: Many parts of India are endemic for the dengue, malaria, typhoid and
scrub typhus infections. The relative contribution of these illnesses in an
outbreak of acute febrile illness is not known in this region. OBJECTIVE: The
present study was conducted to find out the etiological pattern in an epidemic of
acute febrile illness in Uttarakhand during the monsoon period. The study also
focuses on concurrent infections and tries to find out the mortality outcomes.
MATERIALS AND METHODS: A retrospective study of four months was conducted on 1141
patients who presented with fever, and were suspected to have dengue, malaria,
typhoid or scrub typhus. Patients of 12-years of age or above were included in
the study. Serological tests for dengue, malaria, typhoid and scrub typhus were
performed. Slides for malaria parasite were examined. In case of enteric fever
only culture positive cases were included in the study. RESULT: Among the 1141
febrile patients dengue was detected in 812(71.2 %), malaria in 146(12.8%),
typhoid in 92(8.1%) and scrub typhus in 69(6.0%) cases. Mixed infection was noted
in 22(1.9%). CONCLUSION: Maximum (71.2 %) cases of fever were caused by dengue
but significant number (32.3%) of patients suffered from malaria typhoid and
scrub typhus. Many (1.9%) suffered from concurrent and multiple infections.
PMID- 25121014
TI - Microbiological Profile and Drug Sensitivity Pattern among Community Acquired
Pneumonia Patients in Tertiary Care Centre in Mangalore, Coastal Karnataka,
India.
AB - BACKGROUND: Community Acquired Pneumonia (CAP) is the most common respiratory
tract infection in day to day practice. The knowledge of organism commonly
causative of CAP helps in early empirical treatment initiation. AIM: To study the
microbiological profile of patients with community acquired pneumonia and to
study drug sensitivity pattern. METHODS: Hospital based cross sectional study
among 100 patients with CAP was conducted in a tertiary care hospital of Southern
India. Sputum culture showed that out of 100 patients 39 had an identifiable
etiology with 12 patients having evidence of mixed infection. RESULT: Micro
organisms isolated in sputum culture were Streptococcus pneumoniae (31%) followed
by, Pseudomonas pyogens (15%), Klebsiella pneumoniae (13%). AFB smear was found
to be positive in 6 patients. Organisms were found to be sensitive for
piperacillin plus tazobactum (41%), aminoglycocides (amikacin-46%, gentamicin
31%), third generation cephalosporins (Cefotaxim-36%, Ceftriaxone-18%) and
macrolides (Erythromicin-31%, Azithromycin-18%). Sensitivity to chloramphenicol
was observed in 31% sputum culture positive patients. Ciprofloxacin sensitivity
was seen among 49%. CONCLUSION: Most of the organisms were found to be sensitive
to monotherapy with extended spectrum beta lactamases, third generation
cephalosporins, fluroquinolones, macrolides.
PMID- 25121015
TI - Ischaemic Stroke Following Percutaneous Transluminal Coronary Angioplasty (PTCA):
A Rare Complication.
AB - Stroke following coronary interventions is a devastating and most dreaded
complication with significant morbidity and mortality. Various factors have been
ascribed for this complication including the technical errors. We hereby describe
such a patient who presented to us with the diagnosis of acute coronary syndrome
and underwent percutaneous coronary intervention (PCI) but unfortunately
developed left sided hemiparesis due to ischaemic stroke (right middle cerebral
artery). She was managed as per the standard treatment protocols for acute
coronary syndrome and later on for ischaemic stroke which she nicely responded to
and was discharged in a haemodynamically stable condition. On follow-up after 15
days, she was totally symptom-free. We will discuss all the possible preventive
and treatment measures for this rare complication of (PCI).
PMID- 25121016
TI - Bi-opercular Syndrome: A Case Report and Minireview.
AB - Opercular syndrome is a well known but neglected entity and is quite common, but
it is difficult for non-neurologists to diagnose this entity because of lack of
awareness. Inability to speak and swallow with dissociation of automatic
voluntary movements in the affected muscles are the essential features of this
syndrome. The aetiology in most of the reported cases is vascular (thrombosis or
embolism) involving branches of middle cerebral artery supplying the opercular
area. We are reporting a case of "bilateral opercular syndrome" caused by stroke
in a young patient. He had sudden onset of bilateral facial and tongue palsy,
inability to speak and swallow, but with preserved automatic functions. He was
mute but verbal comprehension was normal. CT head revealed bilateral perisylvian
infarcts.
PMID- 25121017
TI - Churg strauss syndrome - a case report.
AB - A male aged 45-years presented with complaints of fever for 7days, cough,
breathlessness for 4 days, tingling of hands, feet and weakness of both hands and
feet for 4 days duration. He was a known asthmatic with history of recurrent
sinusitis in the past. On examination he had bilateral polyphonic wheeze and
evidence of distal asymmetric sensory neuropathy with motor weakness. And on
investigation he had eosinophilia, pulmonary function test showed reversible
airway obstruction,nerve conduction studies revealed mononeuritis multiplex,
muscle biopsy suggestive of eosinophilia infiltration, nerve biopsy suggestive of
vacuities, 2DECHO showed RWMA in inter ventricular septum, Coronary angiogram
showed narrowing in distal LAD territory. In view of sinusitis, asthma,
eosinophilia, tissue infiltration by eosinophils we made a diagnosis of Churg
Strauss syndrome.
PMID- 25121018
TI - Multiple abdominal veins thrombosis secondary to protein s deficiency - a case
report.
AB - Abdominal venous thrombosis may present either as Budd-Chiari syndrome (BCS)
caused by hepatic vein or proximal inferior vena cava (IVC) obstruction or as an
extra hepatic portal obstruction (EHPVO) caused by Portal vein thrombosis or
mesenteric vein thrombosis, but a mixed involvement is uncommon. Multiple
abdominal venous obstructions presenting with thrombosis of hepatic vein, IVC,
portal vein and renal vein are very rarely seen . We are reporting a rare case
with thrombosis of IVC, hepatic vein, portal vein and renal vein, with protein S
and protein C deficiencies, which was managed by giving anticoagulant therapy.
PMID- 25121019
TI - High blood pressure in dialysis patients: cause, pathophysiology, influence on
morbidity, mortality and management.
AB - Dialysis is initiated in a patient with End stage renal disease. The recent
guidelines suggest the initiation of dialysis when symptoms and signs of kidney
failure are present and not merely a decrease in GFR. The most common
complication postdialysis is the occurrence of hypotension. However many dialysis
patients are found to be hypertensive. In this article, we mention the cause and
pathophysiology of hypertension in dialysis patients and its management.
PMID- 25121020
TI - Burden of antibiotic resistance in common infectious diseases: role of antibiotic
combination therapy.
AB - Globally, antimicrobial resistance is alarming concern especially in commonly
reported disease entities like respiratory tract infection, enteric fever and
infections associated with gram-negative bacilli (GNB). Rational use of
antimicrobial drugs reported significant decrease in bacterial burden and may
also reduce the risk of disease progression. However, at times in particular
indication, certain patient and pathogen factor limits the selection and use of
specific antibiotic therapy while in some case, due to presence of additional
risk factor, aggressive therapy is required to achieve clinical reemission and
prevent complications. Delay in start of suitable antibiotic therapy is another
imperative factor for treatment failure and rise of drug resistance. With rapidly
increasing antibiotic resistance and decline in new antibiotic drug development,
the toughest challenge remains to maintain and preserve the efficacy of currently
available antibiotics. Therefore, the best rational approach to fight these
infections is to 'hit early and hit hard' and kills drug-susceptible bacteria
before they become resistant. The preferred approach is to deploy two antibiotics
that produce a stronger effect in combination than if either drug were used
alone. Various society guidelines in particular indications also justify and
recommend the use of combination of antimicrobial therapy. Combination therapies
have distinct advantage over monotherapy in terms of broad coverage, synergistic
effect and prevention of emergence of drug resistance.
PMID- 25121021
TI - Penile incarceration with encircling metallic objects: a study of successful
removal.
AB - OBJECTIVE: This article aimed to study the various treatment options according to
the grading scale for penile incarceration. MATERIALS AND METHODS: A
retrospective review, of all the case files of patients presented with penile
incarceration with encircling metallic object was performed. The patients were
analyzed for age, marital status, motive, object used, who applied it, trauma
grade, duration of incarceration, removal technique, removal time, anesthesia
used and recovery time. RESULT: A total of seven patients were identified. The
average age was 46.71 years. Self-sexual gratification was the most common motive
(five patients). Six patients presented within 24 hours. Grade II of injury was
commonest type of injury seen in five patients.The technique of removal chosen
was according to grade of penile injury, duration of incarceration and type of
object used. Spinal anesthesia was used in most of the cases (five patients).
CONCLUSION: Penile incarceration with encircling metallic objects is a rare
presentation and requires urgent intervention according to trauma grade to
prevent complications.
PMID- 25121022
TI - To study the levels of C - reactive protein and total leucocyte count in patients
operated of open and laparoscopic cholecystectomy.
AB - BACKGROUND: The recovery from laparoscopic cholecystectomy (LC) is rapid and most
of the patients are discharged on the 1st post-operative day. There is an
increased concentration of certain serum proteins, known as acute-phase reactive
proteins (APRP) during the post-operative period depends on the degree of tissue
damage and the inflammatory reaction. There is a direct positive correlation
between the concentrations of APRP, especially C-reactive protein (CRP), and the
severity of inflammation. This study was done to study the levels of C - reactive
protein and Total Leucocyte Count in patients operated either by Open
Cholecystectomy (OC) and Laparoscopic Cholecystectomy (LC). MATERIALS AND
METHODS: This prospective study was conducted on 50 patients after approval from
the Institutional Ethics Committee. Twenty five patients underwent open
cholecystectomy and the other 25 had laparoscopic cholecystectomy. The pre and
post operative concentrations of serum C-reactive protein (CRP) and total
leukocyte count (TLC) were compared in both the groups. RESULTS: There were no
differences in the preoperative serum CRP and TLC concentrations - in both the
groups. Serum CRP rose significantly following OC compared to that of patients
who underwent LC (10.52 +/- 1.96 mg% vs. 8.88 +/- 1.23 mg %). There were also
significant differences in the post-operative TLC ( 9.49 +/- 1.05 m/mm3 for the
OC group vs. 8.57 +/- 1.31 m/mm3 for the LC group), and the post-operative
hospital stay (5.5 +/-1.5 days vs. 1.9 +/- 0.9 days). There was no correlation
between serum CRP concentrations and the other post-operative parameters.
CONCLUSION: The study provided the biochemical evidence supporting the clinical
observation that LC is far less traumatic to the patient than OC.
PMID- 25121023
TI - Clinical examination allied to ultrasonography in the assessment of new onset
gynaecomastia: an observational study.
AB - AIM: New onset gynaecomastia is a relatively common presentation to breast
surgical services. The main aim of clinical and radiological evaluation is to
exclude the presence of concurrent breast cancer. There exists much variability
in the clinical assessment of male patients presenting with new onset
gynaecomastia. MATERIALS AND METHODS: In the presented pilot study, all the male
patients presenting with new onset gynaecomastia to our department over a period
of two years were studied. RESULTS: Fifty three patients presented with new onset
gynaecomastia during the study period. Clinical examination allied with
ultrasonography confirmed benign breast disease in 50 patients with only three
patient requiring breast biopsy to exclude malignancy. We detail the efficacy of
utilising clinical examination in conjunction with ultrasonography to evaluate
new onset gynaecomastia. CONCLUSIONS: We show that clinical examination used in
conjunction with ultrasonography is both highly sensitive and specific for
detecting male breast cancer in patients presenting with new onset gynaecomastia.
PMID- 25121024
TI - Isolated duodenal adenoma presenting as gastrointestinal bleed - a case report.
AB - Duodenal polyps are rare lesions in patients undergoing Esophago-gastro
duodenoscopy (EGD), and the prevalence varies widely with range of 0.3-4.6% of
cases. Duodenal adenomas most commonly occur in association with familial
adenomatous polyposis. Isolated occurrence of such adenomas is very rare and
presentation as upper gastrointestinal (GI) haemorrhage is even rarer. We herein
report a case of elderly male patient presenting to emergency department with
features of upper GI bleeding. Patient was resuscitated followed by EGD was done.
On EGD bleeding duodenal polyp was found and endoscopic polypectomy was done to
control the bleeding. Subsequent colonoscopy was done and was normal. The
histopathological examination of the polypectomy specimen revealed tubular
adenomatous polyp which is a premalignant condition. We also highlight the
clinical presentation, histological types and treatment modalities available in
the literature. However, there is lack of consensus regarding the outcome of
various procedure described in the literature.
PMID- 25121026
TI - Extraocular sebaceous carcinoma on the chest wall - a case report.
AB - Sebaceous carcinoma is a rare aggressive skin cancer derived from the epithelium
of sebaceous glands. Sebaceous carcinomas are generally divided as ocular or
extraocular locations. Very few cases of extra ocular sebaceous carcinomas have
been reported till date. Among them only six cases were reported which were on
the chest wall. We are hereby reporting the seventh case of sebaceous carcinoma
on the chest wall. The disease exhibits diverse clinical presentations and
histologic patterns, often resulting in a delay in an accurate diagnosis as it
may mimic many other cutaneous malignancies like Dermatofibrosarcoma protuberance
Basal Cell Carcinoma or Squamous Cell Carcinoma. High degree of suspicion is
required and sebaceous carcinoma should be considered as one of the differential
diagnosis for an ulceroproliferative growth on the skin.
PMID- 25121025
TI - Isolated splenic hydatidosis.
AB - A 27-year-old female presented with pain in the left hypochondrium for the past
six months. An abdominal examination revealed mild splenomegaly. An abdominal
ultrasonography showed two cystic lesions at the superior pole of the spleen.
Contrast enhanced CT scan abdomen confirmed the USG findings, demonstrating
splenomegaly with nonenhancing cystic lesions having internal septations and
suspicious daughter cysts within it, strongly suggestive of hydatid cysts. On
serological testing, the patient was positive for IgG Antibodies against
Eccinococcus. Following Pneumococcal vaccination, splenectomy was performed
taking precautions to prevent accidental rupture or spillage of contents into the
peritoneum. The postoperative period was uneventful with the patient making a
swift recovery. Histopathological examination revealed extensive necrosis within
the cysts. In the midst of the necrotic material, hooklets were seen. These
features were consistent with a diagnosis of an infected Hydatid cyst. It is of
utmost importance that a correct preop diagnosis is made since all precautions
must be taken to prevent dissemination or seeding of the surgical field. Death
has been reported due to anaphylactic shock resulting from spillage during
excision or biopsy. The most important factor in diagnosing splenic hydatid cyst
is the awareness of its possibility.
PMID- 25121027
TI - Spontaneous Caecal Perforation Associated with Ogilvie's Syndrome Following
Vaginal Delivery - A Case Report.
AB - Acute pseudo-obstruction of the large bowel, Ogilvie's syndrome, can occur in the
postpartum period following caesarean section which can result in caecal
dilatation and may progress to perforation. This is quiet rare following normal
vaginal delivery. Only two previous reports have been found in the English
literature. We report a case of Ogilvie's syndrome with caecal perforation
following normal vaginal delivery.
PMID- 25121028
TI - Myofibroblastoma of female breast masquerading as schirrous malignancy - a rare
case report with review of literature.
AB - Myofibroblastoma is a rare benign mesenchymal tumour of the breast commonly
reported in males. It is a spindle cell neoplasm exhibiting myofibroblastic
differentiation with characteristic immunohistochemical staining. Herein, we
present a case of myofibroblastoma in a premenopausal female which was mimicking
like malignancy clinically. Lump was growing rapidly in size measuring 8 cm x 6
cm and stony hard in consistency. Mammogram showed a large homogeneous hyperdense
lump suggestive of fibroadenoma, Hamartoma and fibromatosis. FNAC and trucut
biopsy of mass could not be done due to stony hard consistency. Hence excision
biopsy was done. Histopathological examination revealed the tumour as
myofibroblastoma. Immunohistochemical staining for markers of myofibroblasts like
CD-34 and Vimentin showed strong positivity. A negative expression for
cytokeratin was noted. This case is presented for its rarity, unusual clinical
presentation and stony hard consistency.
PMID- 25121029
TI - Omental torsion.
AB - Torsion of greater omentum is one of the rare causes of acute abdominal pain. It
can be primary or secondary. Primary Omental Torsion (POT) occurs because a
mobile, thicken segment of omentum rotates around a proximal fixed point in the
absence of any associated or secondary intra-abdominal pathology. Secondary
omental torsion is associated with a number of pre-existing conditions most
common among them is inguinal hernia, other causes include tumours, cysts,
internal or external herniation, foci of intra-abdominal inflammation and
postsurgical wound or scarring. Torsion of omentum causes twisting of omentum
along its long axis resulting in impaired blood supply. This rare condition is
more predominant in middle-aged males. It clinically mimics acute appendicitis.
It should be kept in mind as a differential diagnosis for acute abdomen.
Laparoscopy can aid in diagnosis and management but explorative laparotomy is the
definitive and therapeutic procedure of choice. However the condition is not life
threatening as omentectomy reduces the inflammation and focus of adhesions within
the abdomen.
PMID- 25121030
TI - HBV & HCV - awareness in acute abdomen emergency cases.
AB - A study was conducted on 100 cases of Acute abdomen admitted in surgery
department of Govt Medical college and Rajendra Hospital, Patiala, India. Study
group included patients with different abdominal emergencies, e.g.
gastrointestinal perforation, intestinal obstruction, acute appendicitis, acute
cholecystitis, pancreatitis etc. Out of these, three cases were positive for
HBsAg alone, one for anti Hepatitis C-Virus (HCV) alone and one was positive for
both HBsAg and anti HCV.
PMID- 25121032
TI - Clinico-pathological profile of adnexal torsion cases: a retrospective analysis
from a tertiary care teaching hospital.
AB - INTRODUCTION: Torsion of the adnexa is a rare condition which can be potentially
lethal for the women. The clinical presentation can be varied and can be seen in
any age group. Understanding the clinical and pathological profile of patients
suffering from adenexal torsion can guide the clinicians in diagnosing and
managing the condition. OBJECTIVE: To analyze the clinical and pathological
profile of adnexal torsion cases in a tertiary care teaching hospital. MATERIALS
AND METHODS: The study was a retrospective analysis of hospital records. It
included all cases of adnexal torsion that underwent laprotomy between January
2007 to December 2012 in a tertiary care teaching hospital. The study was
approved by the Institute's human Ethics Committee. RESULTS: A total of 18
patients were included in the study. Majority (66.7%) of participants were in the
reproductive age group. Abdominal pain was the most common symptom seen in 77.8%
of patients. The other symptoms were abdominal distension, back ache and dysuria.
Majority of the women belonged to Para 2 (44.4%) and Para 3 (27.8%). The
proportion of women with one and two LSCS was 11.1% and 16.7% respectively.
Tenderness (38.9%), mass (22.2%) were the common per abdomen findings.
Perspeculum findings were normal in majority (88.9%) of the participants. About
39.2% of the patients presented with a mass in either fornices or pouch of
Douglas on pervaginal examination. The side of lesion was only on right in 9
(50%) , only left in 7(38.9%) and both sides in 2 (11.1%) of cases. On
histopathological examination, of the lesions there were mucinous cystadenoma
(33.3%) serous cystadenoma (16.7%) and benign cystic teratoma (16.7%) as most
common lesions. CONCLUSION: Adnexal torsion, though a rare clinical condition can
present as an emergency most of the times. High index of suspicion is required
for diagnosis, as the clinical presentation can be varied. But the diagnosis can
be made certain only on the operating table, either by laparoscopy. Avoiding a
delay in operating upon the patient will help prevent complications, and aid in
conserving the ovary.
PMID- 25121033
TI - Pregnancy with gilbert syndrome - a case report.
AB - A primigravida presented to us at 32 weeks of gestation with vomiting, myalgia
and jaundice. On examination she had icterus, she was dehydrated, uterus was
corresponding to dates and the fetal heart rate was good. On evaluation, all the
investigations were normal except mild unconjugated hyperbilirubinaemia and
hypoglycaemia. Based on the above findings we derived at a diagnosis of Gilbert
syndrome. Dehydration due to vomiting aggravated her jaundice. On correcting her
dehydration jaundice resolved, patient improved symptomatically and was
discharged two days later. She was later admitted at term and underwent emergency
caesarian section in view of fetal distress. Mother and baby were fine
postoperatively and was discharged on the fifth postoperative day Gilbert
syndrome is rare in obstetric practice. Virtually all patients have decreased
activity of Uridine diphosphate glucuronosyl transferase (UDPGT). The case is
reported due to its rarity.
PMID- 25121031
TI - Knowledge, Awareness and Prevention of Cervical Cancer among Women Attending a
Tertiary Care Hospital in Puducherry, India.
AB - BACKGROUND: Cervical cancer is one of the most common cancers among women
worldwide, with highest mortality in India. The incidence and mortality of
cervical cancer can be reduced by screening women for precancerous lesion and by
administration of human papilloma virus vaccine to adolescent girls. Knowledge of
the women about cervical cancer and awareness about its prevention are the key
factors that determine their utilization of screening services. METHODS: A cross
sectional survey of women attending Gynaecology Out-Patient Department (OPD) in a
tertiary care hospital in Puducherry was conducted. Information about their
knowledge of cervical cancer, awareness of its prevention and their socio
demographic characters were collected. RESULTS: Mean age of the study population
was 40.45 +/- 12 years. Less than half of the study population (178, 44.5%) knew
about cervical cancer. Less than one-fourth of the population knew about
screening services for prevention of cervical cancer, and majority (389, 97.2%)
were not aware of vaccination as prevention for cervical cancer. CONCLUSION: Our
study population shows poor knowledge about cervical cancer and is unaware of the
concept of prevention. Hence extensive health education to the public is needed
regarding cervical cancer and its prevention.
PMID- 25121034
TI - Hypokalemic paraplegia in pregnancy.
AB - Hypokalemic myopathy may range from numbness/weakness to complete paralysis. The
aetiology may be congenital or acquired. It is characterized by acute muscular
weakness with low levels of potassium (<3.5 meq/L). We present a case of 26-year
old multigravida at 36 weeks of gestation with gestational hypertension on
treatment, who came with acute onset of pain, numbness and weakness of both legs
which worsened following betamethasone injection. She was diagnosed to have
Hypokalemic paralysis with potassium levels of 2.1 meq/L. The medical profile
remitted promptly on intravenous potassium replacement. Pregnancy was continued
till 37 weeks with oral potassium supplements, antihypertensives and regular
monitoring of serum potassium levels. The pregnancy was terminated after 37 weeks
in view of gestational hypertension. Postpartum period was uneventful, patient
was discharged after two weeks when potassium levels and BP returned to normal.
PMID- 25121035
TI - A Rare Case of Delayed Pulmonary Oedema due to Methemoglobinemia Following
Laparoscopic Chromopertubation with Methyleneblue.
AB - The patient is a young infertile lady with right tubal block on
hysterosalpingogram was subjected for diagnostic
hysterolaparoscopy.Hysterolaparoscopy findings were normal. Transcervical
chromopertubation was performed using 20 -30 ml of diluted methylene blue through
hysterosalpingogram cannula. Hesitant flow of dye was noted on left side after 2
3 flushing attempts. Ampullary block noted on right side with no spillage of the
dye. Patient made an uneventful anaesthetic recovery. Five hours later patient
developed tachypnea,hypotension and bluish colored urine was drained. She was
shifted to ICU and patient eventually recovered after hemodynamic support with
oxygen, steroids and inotropes. Spectrophotometric analysis showed methemoglobin
levels of 26.3%. This case is reported for its rare but potentially fatal
complication of pulmonary oedema following methylene blue. In this case pulmonary
oedema manifested late in the postoperative period compared to other reported
cases in the literature where pulmonary oedema was seen during intraoperative
period.
PMID- 25121036
TI - Modified pelvic floor repair in prolapsed uterus, with total prevention of vault
prolapse.
AB - In and around Ammapettai, a rural area with an economically backward community,
515 cases were operated for prolapsed uteri, by doing modified pelvic floor
repairs (Dr. Sunthanthradevi's method), without any incidence of vault prolapse,
with patients being followed up for two years after their surgeries.
PMID- 25121037
TI - A rare case of accidental esophageal perforation in an extremely low birth weight
neonate.
AB - Spontaneous perforation of esophagus in neonates is a rare occurrence. However
iatrogenic perforation of the esophagus is not that uncommon, and is most
frequently seen in preterm and low birth weight infants. In premature infants, an
esophageal perforation (EP) mainly occurs while inserting an orogastric tube. The
commonly reported symptoms of EP are sudden onset respiratory distress, due to
the pleural effusion and pneumothorax. In our case neonate presented with apnea
requiring ventilation. We present a rare case of an Extremely Low Birth Weight
(ELBW) neonate with an iatrogenic esophageal perforation who presented with
recurrent apneas, outlining aspects of diagnosis and management.
PMID- 25121038
TI - A case of periodic hypokalemic paralysis in a patient with celiac disease.
AB - A 4-year-old male child presented with recurrent episodes of diarrhoea for 6
months, each episode associated with weakness of all four limbs and documented
hypokalemia who on examination had some pallor, short stature, flaccid
quadriparesis with absent DTR. The patient responded clinically and biochemically
to potassium supplement. TTG and Intestinal biopsy confirmed celiac disease.
Patient was put on gluten free diet and patient is doing well with no recurrence.
We present a case of Recurrent hypokalemic paralysis with previously unsuspected
celiac disease who was not in celiac crisis.
PMID- 25121039
TI - Papillary carcinoma in median aberrant thyroid (ectopic) - case report.
AB - Median ectopic thyroid may be encountered anywhere from the foramen caecum to the
diaphragm. Non lingual median aberrant thyroid (incomplete descent) usually found
in the infrahyoid region and malignant transformation in this ectopic thyroid
tissue is very rare. We report an extremely rare case of papillary carcinoma in
non lingual median aberrant thyroid in a 25-year-old female. The differentiation
between a carcinoma arising in the median ectopic thyroid tissue and a metastatic
papillary carcinoma from an occult primary in the main thyroid gland is also
discussed.
PMID- 25121040
TI - Magnetic resonance imaging (MRI) evaluation of perianal fistulae with surgical
correlation.
AB - AIMS: The purpose of the study was to evaluate the role of Magnetic Resonance
Imaging in detection and characterization of perianal fistulae and correlating it
with surgical findings. METHODS: Fifty consecutive patients with suspected
perianal fistulae having one or more external openings were prospectively
selected for MRI evaluation. Previously operated or patients with recurrent
perianal disease were excluded from the study. MRI findings were recorded
according to "St. James's University Hospital MR Imaging Classification of
Perianal Fistulae" and correlated with surgical observations. Finally, comparison
between T2-weighted fat saturated and postcontrast T1-weighted fat saturated
sequences was done. RESULTS: Amongst the total of 50 patients, per-operative
findings confirmed perianal fistulae in 45 patients. The sensitivity and
specificity of MRI in correctly detecting and grading the primary tract was found
to be 95.56% and 80% respectively; for abscess, it was 87.50% and 95.24%
respectively. High sensitivity was also discerned in identification of secondary
tract (93.75%), correct localization of internal opening (95.83%) and for
correctly detecting the horse-shoeing (87.50%). Our assumption of null hypothesis
was accepted on comparing results of T2-weighted fat saturated sequences and
postcontrast T1-weighted fat saturated sequences. CONCLUSION: Magnetic Resonance
Imaging (MRI) was highly accurate in assessment of surgically important
parameters (primary tract and its grading, internal opening, secondary tract,
abscess, horseshoeing) of perianal fistulae. Comparison of results of imaging
findings on T2-weighted and postcontrast T1-weighted fat saturated sequences were
statistically similar, so contrast study can be omitted, particularly while
evaluating primary / previously unoperated perianal fistulae.
PMID- 25121042
TI - Comparison of 128-Slice Dual Source CT Coronary Angiography with Invasive
Coronary Angiography.
AB - BACKGROUND: Coronary artery disease (CAD) is one of the leading cause of the
morbidity and mortality in India as well as worldwide and last decade has seen a
steep rise in incidence of CAD in India. Direct visualization of the coronary
arteries by invasive catheterization still represents the cornerstone of the
evaluation of CAD. Cardiac imaging is a challenge of 21 (st) century and is being
answered by 128 slice dual source CT as it has good temporal resolution, high
scanning speed as well as low radiation dose. AIM: To assess the diagnostic
accuracy of 128-slice dual source CT Cardiac Angiography in comparison with
Conventional Catheter Cardiac Angiography. MATERIALS AND METHODS: Forty patients
attending the cardiology OPD with complaint of chest pain and suspected of having
CAD were evaluated by CT coronary angiography and conventional invasive Catheter
coronary angiography and the results were compared. All patients were checked for
serum creatinine and ECG before the angiography. Computed Tomography (CT)
coronary angiography was done using SIEMENS 128-slice Dual Source Flash
Definition CT Scanner under either Retrospective or Prospective mode depending on
the heart rate of the patient. Oral/IV beta-blocker were used whenever required.
RESULTS: Coronary arteries were assessed as per 17- segment AHA model. A total of
600/ 609 segments were evaluable in 40 suspected patients on CT coronary
angiography, of which 21 were false positives and 8 were false negatives with
specificity of 95.12% and sensitivity and positive predictive value of 95.26% &
88.46% respectively. CONCLUSION: Non-invasive assessment of CAD is now possible
with high accuracy on 128-slice dual source CT scanner.
PMID- 25121041
TI - Allergic Bronchopulmonary Aspergillosis (ABPA)-The High Resolution Computed
Tomography (HRCT) Chest Imaging Scenario.
AB - INTRODUCTION: Allergic bronchopulmonary aspergillosis (ABPA) is a progressive
disease which can lead to recurrent exacerbations, bronchiectatic changes and end
stage fibrosis. Early diagnosis and treatment prevents its progression and
alleviate its clinical manifestations. High resolution CT of the chest has
emerged as a promising investigation for its diagnosis. AIMS AND OBJECTIVES: To
review the high resolution computed tomography (HRCT) chest manifestations in
ABPA patients. MATERIALS AND METHODS: This study included 110 patients with ABPA
who had undergone HRCT of the chest in the routine diagnostic workup for ABPA.
The scans were assessed for changes in bronchi, parenchyma and pleura and
findings consistent with ABPA were evaluated. RESULTS: HRCT chest was normal in
24 patients. 86 patients demonstrated central bronchiectasis with predilection
for upper and middle lobes. Centrilobular nodules with or without linear
opacities (tree in bud pattern), mucoceles and high-attenuation mucus were seen
in 86%, 59% and 36% patients respectively. CONCLUSION: Central bonchiectasis
combined with centrilobular nodules and mucus impaction (especially high
attenuation mucus) strongly favour the diagnosis of ABPA.
PMID- 25121043
TI - High Resolution Computed Tomography Lung Spectrum in Symptomatic Adult HIV
Positive Patients in South-East Asian Nation.
AB - BACKGROUND: Pulmonary infections remain a leading cause of morbidity and
mortality and one of the most frequent causes of hospital admission in HIV
infected people worldwide. HRCT may be useful in the evaluation of patients with
suspected pulmonary disease. The aim of given study was to determine the High
Resolution Computed Tomography spectrum of lung parenchymal and interstitial
imaging findings in HIV infected patients presented with chest symptoms.
MATERIALS AND METHODS: This study was conducted in a tertiary health care centre,
New Delhi, India. The study consisted of 45 patients. A thorough clinical history
of all the HIV positive patients presenting with suspicion of pulmonary disease
was taken. General physical and respiratory system examination of all patients
was done. HRCT scans of the chest were done in all the cases taken in the study.
RESULTS: Maximum number of patients was in age group 31-40 years (24 cases). Out
of 45 patients included in our study, 32 (71%) were male and 13 (29%) were
female. In our series of 45 patients, 62.2% of patients were diagnosed as having
pulmonary tuberculosis, followed by bacterial infection in 20% cases and
Pneumocystis jiroveci pneumonia (PJP) in 8.9% patients, while 8.9% of the study
did not reveal any significant abnormality. Maximum number (22/28) of patients
with pulmonary tuberculosis were indentified to have nodular opacities. The most
common HRCT finding in bacterial infection was lobar consolidation. The most
common HRCT finding in patients with PCP was diffuse ground glass opacities in
mosaic pattern of distribution. CONCLUSION: HRCT is a highly sensitive tool for
detecting lung parenchymal and interstitial lesions and allows better
characterization of the lesions. HRCT findings should always be correlated with
clinical findings, CD4 counts and other available investigations before arriving
at a diagnosis or differential diagnosis.
PMID- 25121044
TI - Unilateral right pulmonary agenesis in adulthood.
AB - Congenital malformations of the lung, which may vary in degrees of severity, are
very rare diseases. Pulmonary artery agenesis is a rare anomaly that may occur
during the early involution of the proximal portions of the sixth aortic arch,
during embryological development of the heart. This agenesis may be accompained
by a complete or partial absence of the lung and its bronchus on the same side,
which is diagnosed as pulmonary agenesis. In the great majority of the cases, the
diagnosis is usually made at or soon after birth and it can be associated with
multiple anomalies. However, extremely rare asymptomatic cases may go unnoticed
until adulthood. We are presenting a patient with unilateral right pulmonary
agenesis, who survived through adulthood without any symptoms and other
congenital anomalies. The multislice computed tomography findings and
differential diagnoses have been discussed.
PMID- 25121045
TI - Role of CT Imaging with Volume Reconstruction in Hemi Facial Hypertrophy: A
Pediatric Case Report.
AB - Hemifacial hypertrophy is a rare congenital disorder more common in males.It
involves the soft tissue, hard bones and teeth of the face.Its etiology is
unknown and multiple theories have been postulated. We present a 6-year-old male
with hemifacial hypertrophy and describes the importance of CT volume
reconstruction in this condition.
PMID- 25121046
TI - Genetic polymorphism of interleukin-18 gene promoter region in rheumatoid
arthritis patients from southern India.
AB - BACKGROUND: Interleukin-18 (IL-18) is a pro inflammatory cytokine which plays a
key role in the acute and chronic inflammatory phases of Rheumatoid Arthritis
(RA). The Single Nucleotide Polymorphisms (SNPs) of IL-18 gene promoter region at
positions -137 and -607, are postulated to be associated with RA. To test this,
this study aimed to identify the association between these SNPs of the IL-18 gene
promoter region of RA in south Indian patients. MATERIALS AND METHODS: This study
was carried on 190 subjects among which 90 were RA patients and 100 were age and
sex matched controls. Genomic DNA was extracted by Salting out method. IL 18 gene
promotor region SNPs, IL 18 - 607 and IL 18 -137 were amplified by using sequence
specific primers. The amplified products of different samples were separated by
using a 1.5% agarose gel, stained with ethidium bromide and photographed. All
statistical analyses were carried out by using SYSTAT 12 software. RESULTS: At
position 607, the frequencies of C allele, CC genotype, A allele and AA genotype
were found to be significantly higher in patients and controls respectively and
there was no significant difference in CA genotype. At position 137, there was no
significant difference between the two groups with regard to G and C allelles but
there was a significant increase in GG genotype of patients and CC genotype of
controls. There was no association between duration of morning stiffness,
rheumatoid factor positivity or negativity, age of onset and gender with
distribution of genotypes and alleles. CONCLUSION: C allele, CC genotype at
position-607 and GG genotype at position-137 are risk factors and A allele, AA
genotype at position-607 and CC genotype at position-137 have protective effect
for RA.
PMID- 25121047
TI - A Retrospective Clinical Study of the Etiology and Post-operative Visual Outcome
of Rhegmatogenous Retinal Detachment.
AB - AIM: To study the etiology of rhegmatogenous retinal detachment and visual
outcome after retinal detachment surgery. MATERIALS AND METHODS: Retrospective
study conducted at the tertiary eye care hospital over a period of one year.
Thirty eyes of 30 patients were included after fulfilling the inclusion criteria.
Complete ocular examination details of each patient such as visual acuity for
distant vision (checked with Snellen's acuity chart),slit lamp examination,
fundus examination (done with +90D lens) and binocular indirect ophthalmoscopy.
In addition the following were noted: extent of the detachment present, position
and number of breaks, status of the macula, presence of PVR, mobility of retina
and presence of any peripheral retinal degenerations, and fundus photographs of
the patient (before and after surgery). RESULTS: Risk factors for retinal
detachment included myopia in 7 eyes (23.3%), prior cataract surgery in 10 eyes
(33.3%), peripheral retinal degeneration in 3 eyes (10%) and traction with new
vessels in 1 eye (3.3%). Eighteen eyes (60%) presented with macula off while 12
eyes (40%) presented with macula partly or completely attached. Visual acuity at
presentation was <3/60 in 16 eyes. Following surgery, retina was attached in 28
eyes (93.3%) and remained detached in 2 eyes (6.7%). Visual acuity after surgery
was <3/60 in 12 eyes.Visual acuity improved in 13 eyes (43.3%), remained the same
in 16 eyes (53.3%) and worsened in 1 eye (3.3%). CONCLUSION: Myopia and prior
cataract surgery are important risk factors for Rhegmatogenous Retinal
Detachment. Majority of patients in this setting presented late with
Rhegmatogenous Retinal Detachment and this was responsible for relatively poor
visual outcomes despite good anatomical results after surgery. Proper screening
of eyes at risk and education of patients is important for preventing visual loss
due to retinal detachment.
PMID- 25121048
TI - Tryptophan hydroxylase 2 gene polymorphism in anxiety and depressive disorder in
kashmiri population.
AB - BACKGROUND: The gene of tryptophan hydroxylase is widely recognized as a major
candidate gene in many psychiatric disorders. However, no study has been done
which investigates tryptophan hydroxylase 2 gene polymorphism in anxiety and
depressive disorders in Kashmiri population (India). OBJECTIVES: To study
tryptophan hydroxylase 2 (TPH2) C 11993 A gene polymorphism in anxiety and
depressive disorders. METHOD: Sixty patients of depression disorder, 60 patients
of anxiety disorder and 40 unrelated healthy volunteers (control) were studied in
a case control design. Polymorphism was determined using polymerase chain
reaction (PCR) and agarose gel electrophoresis after digestion with HAP II
enzyme. Genotypes and allele frequencies were compared using Chi-square tests,
Fischer's exact test, odds ratio, 95% confidence interval (C.I) and p-value of
<0.05 was considered to be statistical significant. RESULTS: The mean age +/- SD
of anxiety, depression and control group was 32.73+/-10.99, 32.20+/-10 and
29.75+/-10.12 respectively and the difference was found to be statistically non
significant (p=0.349).The mean HAM-A (Hamilton rating scale for anxiety) score
and HAM-D (Hamilton rating scale for depression) score was high in both groups
(anxiety and depression) and found to be statistically significant
(p=0.001).Depression group had AA genotype (55.2%) than control (37.5%) and was
found to be statistically non significant (p=0.890).Comparison of allelic
frequency revealed no association of A allele in anxiety group (76.67%) compared
with control (75.5%) and was found to be statistically non significant (p=
0.866), OR 1.09 (0.56-2.11). CONCLUSION: TPH2C 11993 A gene was not found to be
associated with major depressive disorder (MDD) and anxiety disorder in Kashmiri
population.
PMID- 25121049
TI - Role of information communication technology in higher education: learners
perspective in rural medical schools.
AB - BACKGROUND: Higher education has undergone profound transformation due to recent
technological advancements. Resultantly health profession students have a strong
base to utilize information technology for their professional development.
Studies over recent past reflect a striking change in pattern of technology usage
amongst medical students expanding prospects exponentially by e-books, science
apps, readymade power-point presentations, evidence based medicine, Wikipedia,
etc. Aim & Objectives: The study was undertaken with an aim to explore the
general perceptions of medical students and faculties about the role of
Information Communication Technology in higher education and to gauge student's
dependence on the same for seeking knowledge and information. STUDY DESIGN: Cross
sectional, mixed research design. MATERIALS AND METHODS: The study was conducted
in Department of Physiology, Datta Meghe Institute of Medical Sciences (Deemed
University). Study population included students (n=150) and teaching faculty
(n=10) of I(st) phase of medical curriculum. The survey questionnaire (10 closed
ended and 5 open ended items) and Focus group discussion (FGD) captured the
perceptions and attitudes of students and faculties respectively regarding the
role and relevance of technology in higher education. OBSERVATIONS AND RESULTS:
Quantitative analysis of closed ended responses was done by percentage
distribution and Qualitative analysis of open ended responses and FGD excerpts
was done by coding and observing the trends and patterns respectively. Overall
the observations were in favour of increasing usability and dependability on
technology as ready reference tool of subject information. Learners valued text
books and technology almost equally and regarded computer training as a desirable
incorporation in medical curriculum. CONCLUSION: Role of technology in education
should be anticipated and appropriate measures should be undertaken for its
adequate and optimum utilization by proper training of students as well as
facilitators.
PMID- 25121050
TI - Dermatology Specific Quality of Life in Vitiligo Patients and Its Relation with
Various Variables: A Hospital Based Cross-sectional Study.
AB - INTRODUCTION: Vitiligo is an acquired, idiopathic skin disease characterized by
progressive loss of the inherited skin color. Vitiligo has a special significance
to patients in our country because depigmentation is obvious on dark skin and due
to the enormous stigma that the disease carries. MATERIALS AND METHODS: One
hundred vitiligo patients aged more than 18 years were included in our hospital
based study depending on inclusion and exclusion criteria. All the patients were
asked to fill a validated Hindi version of DLQI questionnaire. DLQI scores and
its interpretation were recorded separately. correlation of DLQI Scores with
different variables like age, body surface area, duration of disease and
socioeconomic status were studied using Pearson's correlations. Mean DLQI scores
were also compared between different groups. RESULTS: Male and female patient
were statistically similar in all variables, like their age, BSA of the
involvement and DLQI score. DLQI interpretation showed that out of 100 patients
of vitiligo, 16 felt no effect of vitiligo on their quality of life while 84
patients reported small to very large effect on their quality of life. Out of
this 84, 37 felt small effects, 21 felt moderate effect and rest 26 felt very
large effect on their quality of life. There was no significant difference among
the different groups mentioned except very large effect on quality of life seen
significantly more in unmarried patients compared to married one. CONCLUSION:
Vitiligo although a cosmetic disease without any symptoms, it carry a significant
social stigma especially in Indian society. Data interpretation in this study
indicates that vitiligo affects QOL in majority of vitiligo patients and such
patients require more aggressive and empathic attitude from a dermatologist to
cure/improve this so called chronic cosmetic disease.
PMID- 25121051
TI - Pretibial Myxedema Associated with Euthyroid Hashimoto's Thyroiditis: A Case
Report.
AB - Pretibial myxedema (PM) is an infiltrative dermopathy which is seen in grave's
disease. It is also associated with hypothyroidism, but is infrequently seen in
Hashimoto's thyroiditis. Lesions are seen commonly over pretibial region as non
pitting oedema or with a plaque morphology. Heat shock protein (HSP) has been
reported to be expressed by fibroblasts present at affected site, which cause
lesions of PM. Histopathology differentiates it from other dermatoses. Lesions
usually resolve spontaneously, but therapies like potent topical steroids,
intralesional steroids, gamma globulin, pentoxifylline, surgery and radiotherapy
are indicated. Here, a case of PM with euthyroid Hashimoto's thyroiditis has been
reported, which was proven by histopathology.
PMID- 25121052
TI - Anything Rare is Possible: Letrozole Induced Eczematous Skin Eruption.
AB - Letrozole is used as first line drug in postmenopausal women with early-stage or
advanced hormone-sensitive breast cancer. Letrozole has favourable tolerability
profile when administered once daily and significant adverse reactions occur
rarely. The objective of this report is to describe a case of eczematous skin
eruption that occurred during letrozole treatment. A 61-year-old female patient
was admitted with lump in the left breast. FNAC, HPE were done and the patient
was diagnosed to have invasive ductal breast carcinoma. After a month of
completing CT and EBRT, the patient was given 2.5 mg OD tab. letrozole at night.
She developed itchy skin lesions over the right thigh that later generalised, at
6- weeks of treatment. The lesion has been defined as eczematous moderate to
severe drug eruption. These lesions were attributed to letrozole therapy and
recurred within 24h after rechallenge. Drug eruption is associated with many
drugs but this is the first such report with letrozole. We suggest of being aware
of such reactions during letrozole usage.
PMID- 25121053
TI - Prevalence of Rubber Dam Usage during Endodontic Procedure: A Questionnaire
Survey.
AB - AIM: To determine the prevalence and frequency of rubber dam usage for endodontic
procedures among general practitioners, specialized practitioners, undergraduate
final year students and Endodontists in the state of Odisha, India. METHODOLOGY:
A pre-piloted questionnaire was distributed among 737 subjects. Dentists and
final year students were surveyed in relation to their prevalence of rubber dam
usage. STATISTICAL ANALYSIS USED: Chi-square/ Fisher Exact tests have been used
to find the significance of study parameters on categorical scale between two or
more groups. RESULTS: Overall response rate was 71%. While about 94% of the
subjects knew the use of rubber dam, 30% have used it for root canal cases and
23% use them for all cases of root canal treatment. Use of rubber dam was 15.4%
in paediatric patients and 34.4% in adult patients. 68% of subjects received
knowledge about rubber dam usage in undergraduate school. 75% felt that rubber
dam should be compulsory before endodontic treatment & 90% were willing to gain
knowledge through training and continuing dental education programs. CONCLUSION:
Whilst rubber dam is used frequently for root canal treatment than operative
treatment, in the present survey there is a low prevalence of its usage during
endodontic therapy. This presents quality issues, as well as medico-legal and
safety concerns for the professional and patients alike. Greater emphasis should
be placed on the advantages of using rubber dam in clinical dentistry at dental
school and through continuing dental education for practitioners to update their
knowledge.
PMID- 25121054
TI - Comparison of coronally advanced and semilunar coronally repositioned flap for
the treatment of gingival recession.
AB - BACKGROUND: Gingival Recession (GR) occurs in population with low oral hygiene
levels. Root coverage may be achieved by a number of surgical techniques,
including pedicle gingival grafts, free grafts, connective tissue grafts, gtr may
also be used. The objective of the present study is to compare the clinical
outcomes of the Semilunar Coronally Repositioned Flap (SCRF) and Coronally
Advanced Flap (CAF) procedure in the treatment of miller's class I gingival
recession defects in maxillary teeth. MATERIALS AND METHODS: Twenty systemically
healthy patients, with isolated miller's class 1 gingival recessions, were
selected and allocated randomly into two groups, Group I and Group II with 10
patients in each. In Group I, the patients were treated with coronally advanced
flap procedure with sling sutures, whereas in Group II, patients were treated
with semilunar coronally repositioned flap without sutures. RESULTS: Descriptive
statistical analysis has been carried out in the present study. RESULTS on
continuous measurements are presented on Mean +/- SD. Significance is assessed at
5 % level of significance. Student t-test (two tailed, dependent) has been used
to find the significance of study parameters between baseline - 3 months and
baseline - 6 months, 90% Confidence interval for mean has been computed.
CONCLUSION: CAF provides consistently better results than SCRF With all other
parameters, such as clinical attachment levels, percentage of root coverage and
complete root coverage and esthetics were taken into account, caf was found to be
superior. In contrary to this, there is significant increase in width of
keratinized tissue in scrf group.
PMID- 25121055
TI - Grading of Extraction and Its Relationship with Post-operative Pain and Trismus,
along with Proposed Grading for Trismus.
AB - BACKGROUND: Extraction of mandibular third molars are somewhat a matter of
interest because of its malpositioning , curved roots, proximity to vital
structures due to this the procedure is often associated with post operative
complications like pain and trismus. The extraction of third molar was classified
in four grads according to the difficulty of the procedure. AIMS: The purpose of
this paper is to find any significant relationship between grading of extraction
and post operative complications like pain and trismus. MATERIALS AND METHODS: A
total number of 180 patients need to go for extraction of third molar was
included in the study. The variables taken into account were grading of
extraction, pain six hour post operatively trismus one day after extraction, and
trismus five day after extraction. The four grades of extractions as described by
Parent in 1974 were statistically analyzed by computing pearson product moment
correlation coefficient with post operative pain and trismus first and fifth day
to find any co relation between them. RESULTS: The grading of extraction was
found significantly correlated with post operative pain, trismus one day after
and fifth day of surgery.
PMID- 25121056
TI - The role and efficacy of herbal antimicrobial agents in orthodontic treatment.
AB - AIMS: To assess the effect of herbal antimicrobial agents on Streptococcus mutans
count in biofilm formations during orthodontic treatment. MATERIALS AND METHODS:
We calculated the growth inhibition of oral bacteria in the orthodontic
appliances after herbal antibacterial agents were placed in culture media. The
Minimum Inhibitory Concentrations (MICs) of these agents on Streptococcus mutans
growth were determined. After cultivating colonies of Streptococci in biofilm
medium with these herbal antimicrobial agents and orthodontic attachments, viable
cell counting was performed from the bacteria which were attached on them.
Scanning electron microscopy (SEM) analysis of morphology was observed on
bacterial cells which were attached to orthodontic attachments. The effects of
these agents were then evaluated and recommendations were forwarded. RESULTS:
There was an increase in count of Streptococcus mutans with respect to the herbal
antibacterial agents. CONCLUSION: Despite the antibacterial functions of these
herbal agents, there was increase in the biofilm formation caused by
Streptococcus mutans to orthodontic bands, which had occurred most likely through
upregulation of glucosyl transferase expression. These extracts may thus play an
important role in increased bacterial attachment to orthodontic wires. Thus, this
study was corroborative of an amalgamation of Ayurvedic therapy and Orthodontic
treatment.
PMID- 25121057
TI - The effect of different chemical surface treatments of denture teeth on shear
bond strength: a comparative study.
AB - BACKGROUND: The development of better cross linked acrylic resin teeth has solved
the problems related to wearing and discoloration of acrylic teeth. The same
cross linking at ridge lap region acts as a double edge sword as it weakens the
bond between denture base and tooth. AIM OF STUDY: The purpose of study was to
evaluate the effect of surface treatment on the bond strength of resin teeth to
denture base resin using monomethyl methacrylate monomer and dichloromethane with
no surface treatment acting as control. SETTINGS AND DESIGN: Denture base
cylinder samples in wax (n=180) were made with maxillary central incisor attached
at 450 (JIST 6506). These samples were randomly and equally divided into three
groups of 60 each. These specimens were then flasked, dewaxed as per the standard
protocol. MATERIALS AND METHODS: Before acrylization, ridge lap area was treated
as follows: Group A- no surface treatment act as control, Group B treated with
monomethyl methacrylate monomer, Group C treated with dichloromethane. Digitally
controlled acryliser was used for acrylization as per manufacturer's instructions
and shear bond strength was tested on Universal Testing Machine (Servo Hydraulic,
50kN High Strain, BISS Research). STATISTICAL ANALYSIS USED: Result was
statistically analyzed with One-way analysis of variance (ANOVA) and Post-hoc
ANOVA Tukey's HSD test at 5% level of significance. RESULTS: The application of
dichloromethane showed increased bond strength between cross linked acrylic resin
teeth and heat cure denture base resin followed by monomethyl methacrylate
monomer and control group. CONCLUSION: The application of dichloromethane on the
ridge lap surface of the resin teeth before packing of the dough into the mold
significantly increased the bond strength between cross linked acrylic resin
teeth and heat cure denture base resin.
PMID- 25121058
TI - Comparison of Salivary Beta Glucuronidase Activity in Chronic Periodontitis
Patients with and without Diabetes Mellitus.
AB - AIM OF THE STUDY: The aim of the study was to estimate the salivary beta
glucuronidase (beta) activity in patients with chronic periodontitis with and
without diabetes mellitus and to evaluate the relationship between Beta
Glucuronidase activity and Periodontal clinical parameters. MATERIALS AND
METHODS: The study consisted of 80 patients of both sexes with age ranging from
20-60 years and they were divided into four groups. Clinical parameters such as
Gingival index, Probing depth and Clinical attachment loss were measured.
Salivary Beta Glucuronidase activity was measured using spectrophotometer with
reagents like phenolphthalein glucuronic acid, phosphate and glycine buffer.
RESULTS: The mean BG activity of Group IV (1.17 +/- 0.27) was significantly
higher than mean BGA levels of Group I, II, III. The p-value was < 0.05. The mean
BGA levels of Group III (0.78 +/- 0.17) was significantly higher than mean BGA
levels of Group I, Group II at 5 % level. There was a significant positive linear
relationship between salivary beta Glucuronidase level and Probing Depth,
clinical attachment level in the experimental Groups. CONCLUSION: The salivary
beta Glucuronidase level was higher in Diabetic patients with periodontitis than
nondiabetic periodontitis patients.
PMID- 25121059
TI - Chlorhexidine chip in the treatment of chronic periodontitis - a clinical study.
AB - AIM: The aim of this study was to clinically evaluate the use of biodegradable
chlorhexidine chip when used as an adjunct to scaling and root planing (SRP) in
the treatment of moderate to severe periodontitis patients. The study also
intended to compare the combined therapy (SRP and Chlorhexidine chip) with
chlorhexidine chip alone in individuals with periodontitis. MATERIALS AND
METHODS: Fifteen patients with three sites having a probing depth of 5-8mm were
considered for the study. Sites were numbered 1, 2, 3 randomly. The clinical
parameters assessed were the Plaque Index (PI), gingival index (GI), Bleeding on
probing (BOP), Clinical attachment level (CAL) and Probing pocket depth (PPD).
Following baseline evaluation, on two sites scaling and root planing (SRP) was
performed, no treatment was carried out in the third site. Chlorhexidine chips
were placed on one site with SRP and another without SRP. A periodontal pack was
placed on the site to prevent dislodgement of the CHX chip. Clinical parameters
were recorded at baseline, one month and three months. Duration of the study was
for three months. STATISTICAL ANALYSIS: T-test and Analysis of variance (ANOVA)
has been carried out in the present study. RESULTS: All three groups presented
with an improvement in the clinical parameters compared to baseline. There was no
statistically significant difference between the SRP and SRP + CHIP group in all
parameters. There was a significant difference when these two groups were
compared to the chip alone group. The mean reductions in PPD were 2.8mm (SRP
group), 2.6 (SRP+CHIP group), 0.8 (chip alone group) The mean gain in CAL were
2.8mm (SRP group), 2.5 (SRP+CHIP group), 0.7 (chip alone group). Reduction in
bleeding on probing were significant for the SRP and SRP +CHIP group but not for
the chip alone group. CONCLUSION: The CHX chip did not provide any clinical
benefit beyond that achieved with conventional scaling and rootplaning after a
three month period.
PMID- 25121061
TI - Ankyloglossia among children of regular and special schools in karnataka, India:
a prevalence study.
AB - BACKGROUND: Tongue-tie (more formally known as ankyloglossia) is a congenital
anomaly characterized by an abnormally short lingual frenulum, which may restrict
the mobility of the tongue tip impairing its ability to fulfil its functions.
Ankyloglossia is uncommon, but not rare. Incidence figures reported in the
literature vary widely, ranging from 0.02% to 4.8%. Incidences of upto 10.7% have
been reported. Since the literature provides no uniformity of information with
regard to the incidence of tongue tie. The aim of this study was to evaluate the
occurrence of tonguetie in general population and mentally challenged population,
measure the grades of tongue-tie and also to determine the relations of gender
with tongue-tie. MATERIALS AND METHODS: Seven hundred school children in the age
group of 9-17 years were examined for the presence of tongue-tie, 350 from
regular schools and 350 from special schools. The presence of tongue-tie was
evaluated, measured and graded into grades 1 to 5 according to KOTLOW's method
and data subjected to statistical analysis. RESULTS: Significantly higher
incidence of 16.4% population having tongue-tie was identified, of which 18.57%
were from general schools and 13.71% from special schools but the differences
were not statistically significant. Males showed greater incidence than females
and grades I, II, III were more predominantly seen than grade IV, but the
differences were not significant statistically. CONCLUSION: Diagnostic criteria
and definitive classifying systems are needed to allow for further comparative
studies.
PMID- 25121060
TI - Effect of Platelet-Rich-Plasma (PRP) and Implant Surface Topography on Implant
Stability and Bone.
AB - PURPOSE: To evaluate the effect of Platelet-Rich-Plasma (PRP) and different
implant surface topography on implant stability and bone levels around
immediately loaded dental implants. MATERIALS AND METHODS: Dental implants were
placed in subjects divided into two groups and four subgroups on basis of implant
treatment with PRP and implant surface topography used. A total of 30 implants
were placed, 15 in each group. For PRP group, implants were placed after surface
treatment with PRP. Temporization was done within two weeks and final prosthesis
was given after three months. Implant stability was measured with Periotest at
baseline, one month and three months. Bone height was measured on mesial & distal
side on standardized IOPA x-rays. RESULTS: A statistically significant difference
was noticed in implant stability with PRP at baseline. The effect of PRP on bone
height changes was not statistically significant. A synergistic effect of PRP and
square thread-form was observed on improved implant stability and bone levels;
however, no such effect is seen with PRP and reverse buttress thread-form.
CONCLUSION: Within the limitation of this study, enhancement on implant stability
and bone healing was observed with PRP treated implant surfaces, and with use of
implant with square thread-form.
PMID- 25121062
TI - Decontamination methods used for dental burs - a comparative study.
AB - AIMS AND OBJECTIVES: Infection control and modes of sterilizations are the key
factors to avoid cross transmission of infection in the field of dentistry.
Transmission of disease or infection is noted with improper sterilization of
reused instruments. Dental burs are the most important tool in any endodontic or
conservative procedures of teeth involving tooth contouring, restorative filling
procedures and endodontic procedures. Hence, the present study is undertaken to
assess the efficacy of different methods of sterilization or decontamination
which are routinely used in dental clinics. MATERIALS AND METHODS: For the
present study 96 round diamond burs were selected and divided into 6 groups.
These burs were used for the access cavity preparation to get contamination and
subjected for bacteriological culture. After getting base line date burs were
subjected to manual scrubbing, hot air oven, glass bead sterilizer, ultrasonic
cleaner and autoclave to get post decontamination data. RESULTS: The study
revealed that mean colony forming units/ml of Streptococcus mutans decreased
maximum for autoclave with 80% reduction, for Lactobacilli 76% reduction and for
Candida albicans maximum reduction seen for glass bead sterilizer with 74%.
CONCLUSION: Findings of our study revealed that none of the methods used were
found to be absolutely efficacious in the decontamination of dental burs.
However, among the experimental groups used in the present study, autoclave was
found to be the relatively best method.
PMID- 25121063
TI - Polarizing and light microscopic analysis of mineralized components and stromal
elements in fibrous ossifying lesions.
AB - INTRODUCTION: Fibro-osseous lesions, along with few reactive lesions of the jaws
exhibit an overlapping histo-morphologic spectrum with respect to the nature of
calcifications and stromal components. This causes difficulty in assessing the
origin, pathogenesis and diagnosis of these lesions. AIM: The present study
analyses the mineralized components, cellularity, stromal density and stromal
composition (nature of collagen, presence of elastic and oxytalan fibres) in
cases of ossifying fibroma (OF), fibrous dysplasia (FD) and peripheral ossifying
fibroma (POF). MATERIALS AND METHODS: The study included a histochemical
evaluation of six cases each of FD, OF and POF. Five consecutive sections of each
case were stained with hematoxylin and eosin, picrosirius red (to assess
maturation of fibres in polarizing light), van Gieson (for area fraction and
collagen density) and aldehyde fuchsin (for elastic and oxytalan fibres)
respectively. RESULTS: Significantly higher amounts of mature bone were seen in
FD while cementicles having microlamellar pattern were predominant in OF and POF
(p < 0.001). Area fraction, collagen density and immature stromal fibre content
was higher in POF followed by FD and OF (p= 0.039). Oxytalan and elastic fibres
were absent in FD. CONCLUSION: Higher cellularity of the stroma in OF was
indicative of its neoplastic behaviour. Higher composition of oxytalan and
elastic fibres in OF and POF supports their periodontal ligament origin. FD was
distinct with more mature fibres in a lamellated bone and absence of oxytalan
fibres.
PMID- 25121064
TI - Combating nasal septum deviation in le fort 1 orthognathic surgery complications,
with submental intubation.
AB - INTRODUCTION: Orthognathic Le Fort 1 osteotomy, a surgical procedure performed to
correct the aesthetics of mid face. Some of the complications of this surgery are
hemorrhage, loss of sensation due to facial nerve damage, nasal septum deviation
leading to crooked nose and snoring. Nasal septum deviation is the most common
complication and one of the most noticeable complications that is developed
during the Le Fort 1 osteotomy. AIM: To ascertain that Submental Intubation in
Orthognathic Le Fort 1 Osteotomy combats Nasal septum Deviation. MATERIALS AND
METHODS: Medical records and clinical data of 32 patients who underwent
orthognathic Le Fort 1 Osteotomy under submental orotracheal intubation were
analyzed to understand if nasal septum deviation and other complications of Le
Fort 1 Osteotomy occurred in such cases based on 6 parameters. RESULTS: No
complications of nasal septum deviation or other complications that's associated
with orthognathic Le Fort 1 Osteotomy were found in the 32 cases that were
analyzed. DISCUSSION: The surgeon needs to have a non-obtrusive nasal canal so as
to determine the extent to which the nasal septum needs to be reduced so that it
does not cause nasal septum deviation post the procedure. Submental oratracheal
intubation provides the surgeon with an excellent view of the operating field,
enough space for intra oral manipulation of the bone and septum for intra oral
operation and control of dental occlusion. CONCLUSION: Submental intubation is a
better method of intubation during Le Fort 1 osteotomy as it does not cause nasal
septum deviation or other associated complications.
PMID- 25121065
TI - Osteosarcoma of the jaws: case report on synchronous multicentric osteosarcomas.
AB - Research has shown that osteosarcomas display high potential for metastasis to
the lungs, pleurae and bones. Mandible, on the other hand, is an uncommon site
for metastatic tumour cell colonization. Nevertheless, a metastatic tumour to
mandible might be the first indication of an undiscovered malignancy at a distant
site. This case report presents a case of a 61-year-old female patient. An
osteosarcoma metastasized to her mandible shortly after the curettage of her jaw
cyst. Both the metastatic osteosarcoma and the jaw cyst were confirmed by
pathology. Initially, bilateral well-defined radiolucent lesions were shown in
her panoramic X-ray image. Also, the diagnosis of a dentigerous cyst was made,
based on histology. Two months later, a mixed radiolucent-radio opaque mass,
which was confirmed as an osteosarcoma by pathology later, occupied the site of
the previously enucleated dentigerous cyst, in her right mandible. Then, an
identical osteosarcoma was found in the left pelvis on further doing overall
radiological and pathological examinations. The pathologic hypotheses, treatment
modality and follow-up of this case have also been presented.
PMID- 25121066
TI - Removable partial denture supported by implants with prefabricated telescopic
abutments - a case report.
AB - Implants have been designed to rehabilitate edentulous patients with fixed
prosthesis or implant supported overdentures. Implant-supported single crowns and
fixed partial dentures have become successful treatment alternatives to removable
and fixed partial dentures. However, it is common to have clinical situations
which make it impossible to use conventional as well as implant supported fixed
partial dentures. The implant supported removable partial dentures can be a
treatment modality that offers the multitude of benefits of implant-based therapy
biologic, biomechanical, social, and psychological to such patients. The aim of
this article is to present a case report describing the fabrication and
advantages of removable partial denture supported by teeth and implants for a
patient with long edentulous span. The patient was satisfied with his dentures in
terms of function and aesthetics. Regular follow-up visits over a period of three
years revealed that the periodontal condition of remaining natural dentition and
peri-implant conditions were stable. There was no evidence of excessive residual
ridge resorption or mobility of the teeth, nor were any visible changes in the
bone levels of the natural teeth or implants noted on radiographs.
PMID- 25121067
TI - Diagnostic CBCT in Dentigerous Cyst with Ectopic Third Molar in the Maxillary
Sinus-A Case Report.
AB - Dentigerous cyst is the second most common odontogenic cyst after radicular cyst.
This report describes a case of a dentigerous cyst associated with an impacted
maxillary third molar. Patient presented with foul smelling discharge through
nose and oral cavity. Cone beam computed tomography revealed maxillary third
molar displaced to lateral wall of the nose and a unilocular radiolucency
obliterating the entire maxillary sinus. A provisional diagnosis of infected
dentigerous cyst was made. The cyst was enucleated along with removal of third
molar. Histopathological examination confirmed the diagnosis of dentigerous cyst.
The patient recovery was uneventful.
PMID- 25121068
TI - A simplified technique for fabrication of orbital prosthesis.
AB - Eye is a vital organ not only for vision, but also an important component of
facial expression, and over-all personality of a person. Loss of eye, apart from
leading to impaired vision has a crippling effect on the psychology of the
patient. Prosthodontic rehabilitation of such cases includes fabrication of
prosthesis by acrylic resin, silicone and implants. However, not all patients are
willing to use implants for maxillofacial rehabilitation. Therefore, a custom
made orbital prosthesis serves as an affordable and satisfactory alternative.
PMID- 25121069
TI - Endodontic treatment of a maxillary first molar with seven root canals confirmed
with cone beam computer tomography - case report.
AB - The most common configuration of the maxillary first molar is the presence of
three roots and four root canals, although the presence of several other
configurations have already been reported. The objective of this work is to
present a rare anatomic configuration with seven root canals diagnosed during an
endodontic therapy. Endodontic treatment was performed using a dental operating
microscope. Exploring the grooves surrounding the main canals with ultrasonic
troughing was able expose unexpected root canals. Instrumentation with files of
smaller sizes and tapers was performed to prevent root physical weakness. The
anatomic configuration was confirmed with a Cone Beam Computer Tomography image
analysis which was able to clearly show the presence of seven root canals. An
electronic database search was conducted to identify all the published similar
cases and the best techniques to approach them are discussed.
PMID- 25121070
TI - Expressly fabricated molar tube bases: enhanced adhesion.
AB - Clinicians, Orthodontists and their patients' parents often expect the best
results in the shortest time span possible. Orthodontic bonding of molar tubes
has been an acceptable risk in a modern era of refined biomaterials and
instrumentation. Although many orthodontists still prefer banding to bonding, it
is the failure rate of the tubes on molars which accounts to an impedance in
molar bonding. One of the reasons for molar attachment failures is attributed to
improper adaptation of the buccal tube base with or without increased thickness
of composite. Merits of banding the second molars especially when these are the
terminal teeth for anchorage have been overemphasized in the literature. The
present article presents a simple and relatively less time consuming technique of
preparing molar tubes to be bonded on tooth surfaces which may be quite difficult
to isolate especially for bonding, for example, mandibular second molars. The
increased surface area of the composite scaffold helps not only in enhanced bond
strength but also serves to reduce the incidence of plaque accumulation given the
dexterity of invitro preparation. The removal of the occlusal part of the molar
tube scaffold helps in prevention of open / raised bite tendencies. The present
innovation, therefore, is not merely serendipity but a structured technique to
overcome a common dilemma for the clinical orthodontist. The present dictum of
banding being superior to molar tube bonding may prove to be futile with
trendsetting molar attachments. It is also an established fact that bonding
proves to be a lesser expensive modality when compared to banding procedures.
PMID- 25121071
TI - Cleidocranial dysplasia: a case report illustrating diagnostic clinical and
radiological findings.
AB - Cleidocranial dysplasia (CCD) is a rare congenital defect, primarily affecting
bones, undergoing intramembranous ossification. CCD presents with skeletal
defects of several bones, the most striking feature of which are partial or
complete absence of clavicles, late fontanels closure, and presence of open skull
sutures and multiple wormian bones. These patients may be first noticed by the
dentist because of the aesthetic problems or delayed eruption of teeth
experienced by the patient. Here, we report a typical case of CCD in a 15-year
old female who had classical diagnostic feature of this syndrome.
PMID- 25121073
TI - Mural adenomatoid odontogenic tumour as anterior mandibular swelling: a
diagnostic challenge.
AB - Adenomatoid odontogenic tumour is an uncommon, benign, hamartomatous lesion that
commonly affects the anterior maxilla and has two radiographic variants,
follicular and extrafollicular where the former is more common than the latter.
Here, we report a case of 15-year-old female with midline swelling of the
mandible. Radiographically, impacted right permanent mandibular canine was
associated with the radiolucent lesion. Dentigerous cyst was given as provisional
diagnosis. However, histologically the lesion represented the features of cystic
variant of Adenomatoid odontogenic tumour.
PMID- 25121072
TI - Management of Dilacerated and S-shaped Root Canals - An Endodontist's Challenge.
AB - The unique morphology of dilacerated and S-shaped root canals often pose utmost
challenges in their endodontic management. Common causes of failures in such
cases are primarily related to procedural errors such as ledges, fractured
instruments, canal blockages, zip and elbow creations. Knowledge of dental
anatomy and its variations is essential for the success of endodontic treatment.
A clinician is required to have an insight of the morphology of tooth related to
its shape, form and structure before commencing treatment. Routine periapical
radiographs aids in assessing these morphological variations in the root canal
system. This article gives a review of the literature and reports an interesting
case of dilacerated and S-shaped root canals of adjacent teeth in the same
patient.
PMID- 25121075
TI - Plasma torch toothbrush a new insight in fear free dentisry.
AB - Dental treatment is considered painful either because of fear or anxiety. Even
though fear and anxiety could be managed; the needle pricks and the heat
generated with drills are both painful and destructive to the tissues of the
tooth. A new technology which can reduce the pain and destruction of the dental
tissues will be of huge value. Plasma torch toothbrush fits into such criteria
and when developed fully, will be able to apply for many of the dental procedures
for increasing the efficiency.
PMID- 25121074
TI - Palliative dental care- a boon for debilitating.
AB - World Health Organization defines "palliative care" as the active total care of
patients whose disease is not responding to curative treatment. Palliative care
actually deals with patients at the terminal end stage of the disease. We always
face a question why a dentist should be in a palliative team? What is the exact
role of dentist? Dental treatment may not always be strenuous and curative, but
also can focus on improving quality of life of the patient. Hence forth the
present paper enlightens the importance of dentist role in palliative team.
PMID- 25121076
TI - Drug therapy trials for the prevention of bronchopulmonary dysplasia: current and
future targets.
PMID- 25121078
TI - Epidemiology of pediatric acute respiratory distress syndrome in singapore: risk
factors and predictive respiratory indices for mortality.
AB - AIM: Acute respiratory distress syndrome (ARDS) represents the most severe form
of acute lung injury. The aim of our study is to describe the epidemiology of
pediatric ARDS in Singapore and compare the outcomes of ARDS using the following
respiratory indices: PaO2/FiO2 ratio (P/F ratio), SpO2/FiO2 ratio (S/F ratio),
oxygenation index (OI), and oxygen saturation index (OSI). METHODS: We examined
medical records of patients admitted to the Children's Intensive Care Unit in KK
Women's and Children's Hospital from 2009 to 2012. Those who fulfilled criteria
for the American-European Consensus Conference definition for ARDS were
identified. Demographic, clinical, and radiographic information were extracted
and analyzed. RESULTS: We identified 70 patients with ARDS. Median age
(interquartile range) was 6.2 (1.4, 10.4) years. The most common risk factor was
pneumonia [50 (71%)]. Overall mortality was 44 (63%) patients. Thirty-two (56%)
patients had an underlying chronic comorbidity; 18 (46%) were hematology-oncology
conditions. Fifty-six (80%) patients had multiorgan dysfunction. Adjunct
therapies used in our patients included inhaled nitric oxide [5 (7%)], prone
position [22 (31%)], steroids [26 (37%)], and neuromuscular blockade [26 (37%)].
A high OI and low PF ratio after 24 h of diagnosis of ARDS were associated with
mortality. From day 3 onward, all four respiratory indices appropriately
differentiated survivors from non-survivors. Severity based on the S/F ratio and
OSI demonstrated association with decreased ventilator free days and ICU free
days. CONCLUSION: Risk factors for mortality included having an underlying
comorbidity, multiorgan dysfunction, a low PF ratio, and high OI at 24 h of ARDS.
Abnormal SpO2-based measurements were reliable markers of poor outcomes in
pediatric ARDS.
PMID- 25121080
TI - Delay in breast cancer: implications for stage at diagnosis and survival.
AB - Breast cancer continues to be a disease with tremendous public health
significance. Primary prevention of breast cancer is still not available, so
efforts to promote early detection continue to be the major focus in fighting
breast cancer. Since early detection is associated with decreased mortality, one
would think that it is important to minimize delays in detection and diagnosis.
There are two major types of delay. Patient delay is delay in seeking medical
attention after self-discovering a potential breast cancer symptom. System delay
is delay within the health care system in getting appointments, scheduling
diagnostic tests, receiving a definitive diagnosis, and initiating therapy.
Earlier studies of the consequences of delay on prognosis tended to show that
increased delay is associated with more advanced stage cancers at diagnosis, thus
resulting in poorer chances for survival. More recent studies have had mixed
results, with some studies showing increased survival with longer delays. One
hypothesis is that diagnostic difficulties could perhaps account for this
survival paradox. A rapidly growing lump may suggest cancer to both doctors and
patients, while a slow growing lump or other symptoms could be less obvious to
them. If this is the case, then the shorter delays would be seen with the more
aggressive tumors for which the prognosis is worse leading to reduced survival.
It seems logical that a tumor that is more advanced at diagnosis would lead to
shorter survival but the several counter-intuitive studies in this review show
that it is dangerous to make assumptions.
PMID- 25121077
TI - Pulmonary manifestations of primary immunodeficiency disorders in children.
AB - Primary immunodeficiencies (PIDs) are inherited disorders in which one or several
components of immune system are decreased, missing, or of non-appropriate
function. These diseases affect the development, function, or morphology of the
immune system. The group of PID comprises more than 200 different disorders and
syndromes and the number of newly recognized and revealed deficiencies is still
increasing. Their clinical presentation and complications depend on the type of
defects and there is a great variability in the relationship between genotypes
and phenotypes. A variation of clinical presentation across various age
categories is also presented and children could widely differ from adult patients
with PID. Respiratory symptoms and complications present a significant cause of
morbidity and also mortality among patients suffering from different forms of
PIDs and they are observed both in children and adults. They can affect primarily
either upper airways (e.g., sinusitis and otitis media) or lower respiratory
tract [e.g., pneumonia, bronchitis, bronchiectasis, and interstitial lung
diseases (ILDs)]. The complications from lower respiratory tract are usually
considered to be more important and also more specific for PIDs and they
determinate patients' prognosis. The spectrum of the causal pathogens usually
demonstrates typical pattern characteristic for each PID category. The
respiratory signs of PIDs can be divided into infectious (upper and lower
respiratory tract infections and complications) and non-infectious (ILDs,
bronchial abnormalities - especially bronchiectasis, malignancies, and benign
lymphoproliferation). Early diagnosis and appropriate therapy can prevent or at
least slow down the development and course of respiratory complications of PIDs.
PMID- 25121079
TI - Existing data analysis in pediatric critical care research.
AB - Our objectives were to review and categorize the existing data sources that are
important to pediatric critical care medicine (PCCM) investigators and the types
of questions that have been or could be studied with each data source. We
conducted a narrative review of the medical literature, categorized the data
sources available to PCCM investigators, and created an online data source
registry. We found that many data sources are available for research in PCCM. To
date, PCCM investigators have most often relied on pediatric critical care
registries and treatment- or disease-specific registries. The available data
sources vary widely in the level of clinical detail and the types of questions
they can reliably answer. Linkage of data sources can expand the types of
questions that a data source can be used to study. Careful matching of the
scientific question to the best available data source or linked data sources is
necessary. In addition, rigorous application of the best available analysis
techniques and reporting consistent with observational research standards will
maximize the quality of research using existing data in PCCM.
PMID- 25121082
TI - Hurricane Sandy: How Did We Do? Assessing a Manhattan Hospital's Response.
PMID- 25121081
TI - Evaluation of capacity-building program of district health managers in India: a
contextualized theoretical framework.
AB - Performance of local health services managers at district level is crucial to
ensure that health services are of good quality and cater to the health needs of
the population in the area. In many low- and middle-income countries, health
services managers are poorly equipped with public health management capacities
needed for planning and managing their local health system. In the south Indian
Tumkur district, a consortium of five non-governmental organizations partnered
with the state government to organize a capacity-building program for health
managers. The program consisted of a mix of periodic contact classes, mentoring
and assignments and was spread over 30 months. In this paper, we develop a
theoretical framework in the form of a refined program theory to understand how
such a capacity-building program could bring about organizational change. A well
formulated program theory enables an understanding of how interventions could
bring about improvements and an evaluation of the intervention. In the refined
program theory of the intervention, we identified various factors at individual,
institutional, and environmental levels that could interact with the hypothesized
mechanisms of organizational change, such as staff's perceived self-efficacy and
commitment to their organizations. Based on this program theory, we formulated
context-mechanism-outcome configurations that can be used to evaluate the
intervention and, more specifically, to understand what worked, for whom and
under what conditions. We discuss the application of program theory development
in conducting a realist evaluation. Realist evaluation embraces principles of
systems thinking by providing a method for understanding how elements of the
system interact with one another in producing a given outcome.
PMID- 25121084
TI - Where India stands in malaria elimination?
PMID- 25121083
TI - Discharge beta-Blocker Use and Race after Coronary Artery Bypass Grafting.
AB - INTRODUCTION: The use of discharge beta-blockers after cardiac surgery is
associated with a long-term mortality benefit. beta-Blockers have been suggested
to be less effective in black cardiovascular patients compared with whites. To
date, racial differences in the long-term survival of coronary artery bypass
grafting (CABG) patients who receive beta-blockers at discharge have not been
examined. METHODS: A retrospective cohort study was conducted on patients
undergoing CABG between 2002 and 2011. Long-term survival was compared in
patients who were and who were not discharged with beta-blockers. Hazard ratios
(HR) and 95% confidence intervals (CI) were computed using a Cox regression
model. P-for-interaction between race and discharge beta-blocker use was computed
using a likelihood ratio test. RESULTS: A total of 853 (88%) black (n = 970) and
3,038 (88%) white (n = 3,460) patients had a history of beta-blocker use at
discharge (N = 4,430). Black patients who received beta-blockers survived longer
than those not receiving beta-blockers and the survival advantage was comparable
with white patients (black, adjusted HR = 0.33, 95% CI = 0.23-0.46; white,
adjusted HR = 0.48, 95% CI = 0.39-0.58; p-for-interaction = 0.74). Among patients
discharged on beta-blockers, we did not observe a long-term survival advantage
for white compared with black patients (HR = 1.2, 95% CI = 0.95-1.5). CONCLUSION:
beta-Blocker use at discharge was associated with a survival advantage among
black patients after CABG and a similar association was observed in white
patients.
PMID- 25121085
TI - Problems and their solutions in genetic counseling education in Japan.
AB - With the expansion of novel chromosome testing, a career as a certified genetic
counselor has been gathering a lot of attention. However, few people certified as
a genetic counselor after completing postgraduate courses are able to find
employment as a genetic counselor, and their salaries are quite low. It is also
questionable whether or not such newly graduated genetic counselors, who have
limited life experience and knowledge, can fully understand family issues and
properly perform counseling sessions. To address these issues, a wide range of
education and training may be necessary. In this study, we examined current
problems in genetic counseling education in Japan, and proposed effective
measures to address these problems. Toward creating a new society, we are
currently establishing a national qualification system and cultivating qualified
professionals capable of providing patients with accurate information on
chromosome and genetic testing. In addition, these professionals could encourage
younger generations to have an interest in genetic counseling. I also hope that
these professionals will work not only in Japan but all over the world.
PMID- 25121086
TI - Novel TPP-riboswitch activators bypass metabolic enzyme dependency.
AB - Riboswitches are conserved regions within mRNA molecules that bind specific
metabolites and regulate gene expression. TPP-riboswitches, which respond to
thiamine pyrophosphate (TPP), are involved in the regulation of thiamine
metabolism in numerous bacteria. As these regulatory RNAs are often modulating
essential biosynthesis pathways they have become increasingly interesting as
promising antibacterial targets. Here, we describe thiamine analogs containing a
central 1,2,3-triazole group to induce repression of thiM-riboswitch dependent
gene expression in different E. coli strains. Additionally, we show that compound
activation is dependent on proteins involved in the metabolic pathways of
thiamine uptake and synthesis. The most promising molecule, triazolethiamine
(TT), shows concentration dependent reporter gene repression that is dependent on
the presence of thiamine kinase ThiK, whereas the effect of pyrithiamine (PT), a
known TPP-riboswitch modulator, is ThiK independent. We further show that this
dependence can be bypassed by triazolethiamine-derivatives that bear phosphate
mimicking moieties. As triazolethiamine reveals superior activity compared to
pyrithiamine, it represents a very promising starting point for developing novel
antibacterial compounds that target TPP-riboswitches. Riboswitch-targeting
compounds engage diverse endogenous mechanisms to attain in vivo activity. These
findings are of importance for the understanding of compounds that require
metabolic activation to achieve effective riboswitch modulation and they enable
the design of novel compound generations that are independent of endogenous
activation mechanisms.
PMID- 25121087
TI - N-alkynyl derivatives of 5-fluorouracil: susceptibility to palladium-mediated
dealkylation and toxigenicity in cancer cell culture.
AB - Palladium-activated prodrug therapy is an experimental therapeutic approach that
relies on the unique chemical properties and biocompatibility of heterogeneous
palladium catalysis to enable the spatially-controlled in vivo conversion of a
biochemically-stable prodrug into its active form. This strategy, which would
allow inducing local activation of systemically administered drug precursors by
mediation of an implantable activating device made of Pd(0), has been proposed by
our group as a way to reach therapeutic levels of the active drug in the affected
tissue/organ while reducing its systemic toxicity. In the seminal study of such
an approach, we reported that propargylation of the N1 position of 5-fluorouracil
suppressed the drug's cytotoxic properties, showed high stability in cell culture
and facilitated the bioorthogonal restoration of the drug's pharmacological
activity in the presence of extracellular Pd(0)-functionalized resins. To provide
additional insight on the properties of this system, we have investigated
different N1-alkynyl derivatives of 5-fluorouracil and shown that the presence of
substituents near the triple bond influence negatively on its sensitivity to
palladium catalysis under biocompatible conditions. Comparative studies of the N1
vs. the N3-propargyl derivatives of 5-fluorouracil revealed that masking each or
both positions equally led to inactive derivatives (>200-fold reduction of
cytotoxicity relative to the unmodified drug), whereas the depropargylation
process occurred faster at the N1 position than at the N3, thus resulting in
greater toxigenic properties in cancer cell culture.
PMID- 25121088
TI - Associations of CTLA4 Gene Polymorphisms with Graves' Ophthalmopathy: A Meta
Analysis.
AB - Many studies have established that T-lymphocyte antigen-4 (CTLA4) is a
susceptible gene for Graves' disease (GD). Also many studies showed the
association between the CTLA4 exon-1 49A/G polymorphism and the risk of
developing Graves' ophthalmopathy (GO) in GD patients. But those results were
inconsistent. In recent years many new studies were published which helped to
shed light on the relationship of CTLA4 SNP49 with GO. So we performed the meta
analysis to explore the association between the SNP49 and GO susceptibility in GD
patients. Studies up to February 29, 2012, were searched by using PubMed. The
odds ratio was used to evaluate the strength of the association. Altogether 12
case-control studies involving 2,505 participants were included in the meta
analysis. Results showed that the G allele was related to the increased risk of
GO compared with the A allele under allelic genetic model (OR = 1.14, 95% CI:
1.14-1.72, P = 0.001) in European subgroup. No publication bias was detected. Our
results showed that the SNP49 polymorphism of CTLA4 gene was related to increased
risk of GO.
PMID- 25121089
TI - Comparative Analysis of Glycogene Expression in Different Mouse Tissues Using RNA
Seq Data.
AB - Glycogenes regulate a wide array of biological processes in the development of
organisms as well as different diseases such as cancer, primary open-angle
glaucoma, and renal dysfunction. The objective of this study was to explore the
role of differentially expressed glycogenes (DEGGs) in three major tissues such
as brain, muscle, and liver using mouse RNA-seq data, and we identified 579, 501,
and 442 DEGGs for brain versus liver (BvL579), brain versus muscle (BvM501), and
liver versus muscle (LvM442) groups. DAVID functional analysis suggested
inflammatory response, glycosaminoglycan metabolic process, and protein
maturation as the enriched biological processes in BvL579, BvM501, and LvM442,
respectively. These DEGGs were then used to construct three interaction networks
by using GeneMANIA, from which we detected potential hub genes such as PEMT and
HPXN (BvL579), IGF2 and NID2 (BvM501), and STAT6 and FLT1 (LvM442), having the
highest degree. Additionally, our community analysis results suggest that the
significance of immune system related processes in liver, glycosphingolipid
metabolic processes in the development of brain, and the processes such as cell
proliferation, adhesion, and growth are important for muscle development. Further
studies are required to confirm the role of predicted hub genes as well as the
significance of biological processes.
PMID- 25121090
TI - New acquisition protocol of 18F-choline PET/CT in prostate cancer patients:
review of the literature about methodology and proposal of standardization.
AB - PURPOSE: (1) To evaluate a new acquisition protocol of (18)F-choline (FCH) PET/CT
for prostate cancer patients (PC), (2) to review acquisition (18)F-choline PET/CT
methodology, and (3) to propose a standardized acquisition protocol on FCH PET/CT
in PC patients. MATERIALS: 100 consecutive PC patients (mean age 70.5 years, mean
PSA 21.35 ng/mL) were prospectively evaluated. New protocol consisted of an early
scan of the pelvis immediately after the injection of the tracer (1 bed position
of 4 min) followed by a whole body scan at one 1 hour. Early and 1 hour images
were compared for interfering activity and pathologic findings. RESULTS: The
overall detection rate of FCH PET/CT was 64%. The early static images of the
pelvis showed absence of radioactive urine in ureters, bladder, or urethra which
allowed a clean evaluation of the prostatic fossae. Uptake in the prostatic
region was better visualized in the early phase in 26% (7/30) of cases. Other
pelvic pathologic findings (bone and lymph nodes) were visualized in both early
and late images. CONCLUSION: Early (18)F-choline images improve visualization of
abnormal uptake in prostate fossae. All pathologic pelvic deposits (prostate,
lymph nodes, and bone) were visualized in both early and late images.
PMID- 25121091
TI - Effects of converting tacrolimus formulation from twice-daily to once-daily in
liver transplantation recipients.
AB - Typically, tacrolimus is administrated twice daily. Prolonged-release tacrolimus
is the once-daily formulation and may be more convenient for patients. Experience
with the administration of the once-daily formulation is still limited. This
study enrolled 210 liver transplant recipients who had stable liver function and
converted tacrolimus from a twice-daily to once-daily formulation on a 1 mg to 1
mg basis. Among 210 patients, seven patients (3.3%) were withdrawn from the once
daily formulation due to allergy and fatigue. For the other patients, the trough
concentration after converting to the once-daily formulation was lower than that
of the twice-daily formulation. Liver enzymes were mildly elevated in 3 months
after formulation conversion and serum creatinine and uric acid were mildly
decreased. Seven patients (3.4%) had clinical suspicion of acute rejection after
the formulation conversion and three of them were caused by nonadherence. 155
patients (76.4%) experienced a more convenient life with an increase of social
activity. Forty-seven patients (23.2%) experienced the convenience of once-daily
formulation during overseas trips. In conclusion, tacrolimus can be safely
converted from the twice-daily to the once-daily formulation for most stable
liver recipients. Acute rejection may occur in a minority of patients during
formulation conversion and should be carefully monitored.
PMID- 25121092
TI - Expression of acetylcholine receptors by experimental rat renal allografts.
AB - Chronic allograft injury (CAI) is a major cause for renal allograft dysfunction
and characterized by vasculopathies, tubular atrophy, and fibrosis. We
demonstrated that numerous leukocytes interact with vascular endothelial cells of
allografts and produce acetylcholine, which contributes to vascular remodeling.
The cholinergic system might be a promising target for the development of novel
therapies. However, neither the cellular mechanisms nor the acetylcholine
receptors involved in CAI are known. Kidney transplantation was performed in the
Lewis to Lewis and in the Fischer-334 to Lewis rat strain combination, which is
an established experimental model for CAI. Expression of nicotinic and muscarinic
acetylcholine receptors mRNA was quantified in renal tissue by real-time RT-PCR
on days 9 and 42 after surgery. We detected CHRNA2-7, CHRNA10, CHRNB2, CHRNB4,
and CHRM1-3 mRNA in normal kidneys and in renal transplants. In contrast, CHRNA9,
CHRM4, and CHRM5 mRNA remained below the threshold of detection. In renal
allografts, CHRNA3 and CHRNB4 mRNA expression were dramatically reduced compared
to isografts. In conclusion, we demonstrated that most acetylcholine receptor
subtypes are expressed by normal and transplanted kidneys. Allograft rejection
downmodulates CHRNA3 and CHRNB4 mRNA. The role of different acetylcholine
receptor subtypes in the development of CAI remains to be established.
PMID- 25121093
TI - Gonadal transcriptome analysis of male and female olive flounder (Paralichthys
olivaceus).
AB - Olive flounder (Paralichthys olivaceus) is an important commercially cultured
marine flatfish in China, Korea, and Japan, of which female grows faster than
male. In order to explore the molecular mechanism of flounder sex determination
and development, we used RNA-seq technology to investigate transcriptomes of
flounder gonads. This produced 22,253,217 and 19,777,841 qualified reads from
ovary and testes, which were jointly assembled into 97,233 contigs. Among them,
23,223 contigs were mapped to known genes, of which 2,193 were predicted to be
differentially expressed in ovary and 887 in testes. According to annotation
information, several sex-related biological pathways including ovarian
steroidogenesis and estrogen signaling pathways were firstly found in flounder.
The dimorphic expression of overall sex-related genes provides further insights
into sex determination and gonadal development. Our study also provides an
archive for further studies of molecular mechanism of fish sex determination.
PMID- 25121094
TI - Promoting nerve regeneration in a neurotmesis rat model using poly(DL-lactide
epsilon-caprolactone) membranes and mesenchymal stem cells from the Wharton's
jelly: in vitro and in vivo analysis.
AB - In peripheral nerves MSCs can modulate Wallerian degeneration and the overall
regenerative response by acting through paracrine mechanisms directly on
regenerating axons or upon the nerve-supporting Schwann cells. In the present
study, the effect of human MSCs from Wharton's jelly (HMSCs), differentiated into
neuroglial-like cells associated to poly (DL-lactide-epsilon-caprolactone)
membrane, on nerve regeneration, was evaluated in the neurotmesis injury rat
sciatic nerve model. Results in vitro showed successful differentiation of HMSCs
into neuroglial-like cells, characterized by expression of specific neuroglial
markers confirmed by immunocytochemistry and by RT-PCR and qPCR targeting
specific genes expressed. In vivo testing evaluated during the healing period of
20 weeks, showed no evident positive effect of HMSCs or neuroglial-like cell
enrichment at the sciatic nerve repair site on most of the functional and nerve
morphometric predictors of nerve regeneration although the nociception function
was almost normal. EPT on the other hand, recovered significantly better after
HMSCs enriched membrane employment, to values of residual functional impairment
compared to other treated groups. When the neurotmesis injury can be surgically
reconstructed with an end-to-end suture or by grafting, the addition of a PLC
membrane associated with HMSCs seems to bring significant advantage, especially
concerning the motor function recovery.
PMID- 25121095
TI - Novel approach to reactive oxygen species in nontransfusion-dependent
thalassemia.
AB - The term Nontransfusion dependent thalassaemia (NTDT) was suggested to describe
patients who had clinical manifestations that are too severe to be termed minor
yet too mild to be termed major. Those patients are not entirely dependent on
transfusions for survival. If left untreated, three main factors are responsible
for the clinical sequelae of NTDT: ineffective erythropoiesis, chronic hemolytic
anemia, and iron overload. Reactive oxygen species (ROS) generation in NTDT
patients is caused by 2 major mechanisms. The first one is chronic hypoxia
resulting from chronic anemia and ineffective erythropoiesis leading to
mitochondrial damage and the second is iron overload also due to chronic anemia
and tissue hypoxia leading to increase intestinal iron absorption in thalassemic
patients. Oxidative damage by reactive oxygen species (generated by free globin
chains and labile plasma iron) is believed to be one of the main contributors to
cell injury, tissue damage, and hypercoagulability in patients with thalassemia.
Independently increased ROS has been linked to a myriad of pathological outcomes
such as leg ulcers, decreased wound healing, pulmonary hypertension, silent brain
infarcts, and increased thrombosis to count a few. Interestingly many of those
complications overlap with those found in NTDT patients.
PMID- 25121096
TI - TBT effects on the development of intersex (ovotestis) in female fresh water
prawn Macrobrachium rosenbergii.
AB - The impact of tributyltin (TBT) on the female gonad and the endocrine system in
Macrobrachium rosenbergii was studied. Prawns were exposed to environmentally
realistic concentrations of 10, 100, and 1000 ng/L of TBT for 6 months. Dose
dependent effects were noticed in TBT exposed prawns. At 1000 ng/L TBT caused
ovotestis formation (formation of male germ cells in ovary). Presence immature
oocytes, fusion of developing oocytes, increase in interstitial connective
tissues, and its modification into tubular like structure and abundance of
spermatogonia in the ovary of TBT treated prawns. The control prawn ovary showed
normal architecture of cellular organelles such as mature oocytes with type 2
yolk globules, lipid droplets, normal appearance of yolk envelop, and uniformly
arranged microvilli. On the other hand, type 1 yolk globules, reduced size of
microvilli, spermatogonial cells in ovary, spermatogonia with centrally located
nucleus, and chromatin distribution throughout the nucleoplasm were present in
the TBT treated group. Immunofluorescence staining indicated a reduction in
vitellin content in ovary of TBT treated prawn. Moreover, TBT had inhibited the
vitellogenesis by causing hormonal imbalance in M. rosenbergii. Thus, the present
investigation demonstrates that TBT substantially affects sexual differentiation
and gonadal development in M. rosenbergii.
PMID- 25121097
TI - Caspase-14 expression impairs retinal pigment epithelium barrier function:
potential role in diabetic macular edema.
AB - We recently showed that caspase-14 is a novel molecule in retina with potential
role in accelerated vascular cell death during diabetic retinopathy (DR). Here,
we evaluated whether caspase-14 is implicated in retinal pigment epithelial cells
(RPE) dysfunction under hyperglycemia. The impact of high glucose (HG, 30 mM D
glucose) on caspase-14 expression in human RPE (ARPE-19) cells was tested, which
showed significant increase in caspase-14 expression compared with normal glucose
(5 mM D-glucose + 25 mM L-glucose). We also evaluated the impact of modulating
caspase-14 expression on RPE cells barrier function, phagocytosis, and activation
of other caspases using ARPE-19 cells transfected with caspase-14 plasmid or
caspase-14 siRNA. We used FITC-dextran flux assay and electric cell substrate
impedance sensing (ECIS) to test the changes in RPE cell barrier function.
Similar to HG, caspase-14 expression in ARPE-19 cells increased FITC-dextran
leakage through the confluent monolayer and decreased the transcellular
electrical resistance (TER). These effects of HG were prevented by caspase-14
knockdown. Furthermore, caspase-14 knockdown prevented the HG-induced activation
of caspase-1 and caspase-9, the only activated caspases by HG. Phagocytic
activity was unaffected by caspase-14 expression. Our results suggest that
caspase-14 contributes to RPE cell barrier disruption under hyperglycemic
conditions and thus plays a role in the development of diabetic macular edema.
PMID- 25121099
TI - Validity and reliability of the Bahasa Melayu version of the Migraine Disability
Assessment questionnaire.
AB - BACKGROUND: The study was designed to determine the validity and reliability of
the Bahasa Melayu version (MIDAS-M) of the Migraine Disability Assessment (MIDAS)
questionnaire. METHODS: Patients having migraine for more than six months
attending the Neurology Clinic, Hospital Universiti Sains Malaysia, Kubang
Kerian, Kelantan, Malaysia, were recruited. Standard forward and back translation
procedures were used to translate and adapt the MIDAS questionnaire to produce
the Bahasa Melayu version. The translated Malay version was tested for face and
content validity. Validity and reliability testing were further conducted with
100 migraine patients (1st administration) followed by a retesting session 21
days later (2nd administration). RESULTS: A total of 100 patients between 15 and
60 years of age were recruited. The majority of the patients were single (66%)
and students (46%). Cronbach's alpha values were 0.84 (1st administration) and
0.80 (2nd administration). The test-retest reliability for the total MIDAS score
was 0.73, indicating that the MIDAS-M questionnaire is stable; for the five
disability questions, the test-retest values ranged from 0.77 to 0.87.
CONCLUSION: The MIDAS-M questionnaire is comparable with the original English
version in terms of validity and reliability and may be used for the assessment
of migraine in clinical settings.
PMID- 25121100
TI - Prevalence and correlation between TMD based on RDC/TMD diagnoses, oral
parafunctions and psychoemotional stress in Polish university students.
AB - The aim of the study was to assess the prevalence of temporomandibular disorders
(TMD) and oral parafunctions, as well as their correlation with psychoemotional
factors in Polish university students. The research was conducted in a group of
456 students (N = 456). The examination form comprised of two parts: survey and
clinical examination. The research diagnostic criteria for temporomandibular
disorders (RDC/TMD) was used in order to assess TMD. Symptoms of TMD were
observed in 246 (54%) students after clinical examination. The largest group
involved students with disc displacement (women: 132, 29%; men: 70, 15%). Women
(164; 36%) suffered more frequently than men (82; 18%) from problems related to
the stomatognathic system (P < 0.05), described themselves as easily excitable
and emotionally burdened, and reported symptoms as tightness of the facial and
neck muscles (P < 0.05). In 289 (64%) students intraoral symptoms concerning
occlusal parafunctions were observed. In 404 (89%) examined students, nonocclusal
parafunctions were recorded. A significant correlation between TMD and
psychoemotional problems could be detected. TMD symptoms more often concern
women. Emotional burden and excitability are factors predisposing muscular
disorders.
PMID- 25121098
TI - Cell death and deubiquitinases: perspectives in cancer.
AB - The process of cell death has important physiological implications. At the
organism level it is mostly involved in maintenance of tissue homeostasis. At the
cellular level, the strategies of cell death may be categorized as either suicide
or sabotage. The mere fact that many of these processes are programmed and that
these are often deregulated in pathological conditions is seed to thought. The
various players that are involved in these pathways are highly regulated. One of
the modes of regulation is via post-translational modifications such as
ubiquitination and deubiquitination. In this review, we have first dealt with the
different modes and pathways involved in cell death and then we have focused on
the regulation of several proteins in these signaling cascades by the different
deubiquitinating enzymes, in the perspective of cancer. The study of
deubiquitinases is currently in a rather nascent stage with limited knowledge
both in vitro and in vivo, but the emerging roles of the deubiquitinases in
various processes and their specificity have implicated them as potential targets
from the therapeutic point of view. This review throws light on another aspect of
cancer therapeutics by targeting the deubiquitinating enzymes.
PMID- 25121101
TI - Hepatic chemerin and chemokine-like receptor 1 expression in patients with
chronic hepatitis C.
AB - INTRODUCTION: Chemerin seems to be involved in pathogenesis of chronic hepatitis
C (CHC). Hepatic expressions of chemerin and its receptor, chemokine receptor
like 1 (CMKLR1), in CHC have not been studied so far. AIM: To evaluate chemerin
and CMKLR1 hepatic expression together with serum chemerin concentration in CHC
patients and to assess their relationship with metabolic and histopathological
abnormalities. METHODS: The study included 63 nonobese CHC patients.
Transcription of chemerin and CMKLR1 was assessed by quantitative real-time PCR,
while serum chemerin was assessed by enzyme-linked immunosorbent assay. RESULTS:
Expression of chemerin and CMKLR1 was present in the liver of all CHC patients
regardless of sex or age. This expression was not associated with
necroinflammatory activity and steatosis grade, fibrosis stage, and metabolic
abnormalities. There was a negative association between serum chemerin and
chemerin hepatic expression (r = (-0.41), P = 0.006). CONCLUSION: The study for
the first time confirmed a marked expression of chemerin and CMKLR1 in the liver
of CHC patients. The study was performed using the homogenates of human liver
tissue, so it is not possible to define whether hepatocytes or other cell types
which are abundantly represented in the liver constitute the main source of
chemerin and CMKLR1 mRNA.
PMID- 25121102
TI - Fungi treated with small chemicals exhibit increased antimicrobial activity
against facultative bacterial and yeast pathogens.
AB - For decades, fungi have been the main source for the discovery of novel
antimicrobial drugs. Recent sequencing efforts revealed a still high number of so
far unknown "cryptic" secondary metabolites. The production of these metabolites
is presumably epigenetically silenced under standard laboratory conditions. In
this study, we investigated the effect of six small mass chemicals, of which some
are known to act as epigenetic modulators, on the production of antimicrobial
compounds in 54 spore forming fungi. The antimicrobial effect of fungal samples
was tested against clinically facultative pathogens and multiresistant clinical
isolates. In total, 30 samples of treated fungi belonging to six different genera
reduced significantly growth of different test organisms compared to the
untreated fungal sample (growth log reduction 0.3-4.3). For instance, the pellet
of Penicillium restrictum grown in the presence of butyrate revealed significant
higher antimicrobial activity against Staphylococcus (S.) aureus and
multiresistant S. aureus strains and displayed no cytotoxicity against human
cells, thus making it an ideal candidate for antimicrobial compound discovery.
Our study shows that every presumable fungus, even well described fungi, has the
potential to produce novel antimicrobial compounds and that our approach is
capable of rapidly filling the pipeline for yet undiscovered antimicrobial
substances.
PMID- 25121103
TI - Stem cell based gene therapy in prostate cancer.
AB - Current prostate cancer treatment, especially hormone refractory cancer, may
create profound iatrogenic outcomes because of the adverse effects of cytotoxic
agents. Suicide gene therapy has been investigated for the substitute modality
for current chemotherapy because it enables the treatment targeting the cancer
cells. However the classic suicide gene therapy has several profound side
effects, including immune-compromised due to viral vector. Recently, stem cells
have been regarded as a new upgraded cellular vehicle or vector because of its
homing effects. Suicide gene therapy using genetically engineered mesenchymal
stem cells or neural stem cells has the advantage of being safe, because prodrug
administration not only eliminates tumor cells but consequently kills the more
resistant therapeutic stem cells as well. The attractiveness of prodrug cancer
gene therapy by stem cells targeted to tumors lies in activating the prodrug
directly within the tumor mass, thus avoiding systemic toxicity. Therapeutic
achievements using stem cells in prostate cancer include the cytosine deaminase/5
fluorocytosine prodrug system, herpes simplex virus thymidine kinase/ganciclovir,
carboxyl esterase/CPT11, and interferon-beta. The aim of this study is to review
the stem cell therapy in prostate cancer including its proven mechanisms and also
limitations.
PMID- 25121104
TI - Antidiabetic activity of Acacia tortilis (Forsk.) Hayne ssp. raddiana
polysaccharide on streptozotocin-nicotinamide induced diabetic rats.
AB - The present study was designed to investigate the antidiabetic activity of
aqueous extract of Acacia tortilis polysaccharide (AEATP) from gum exudates and
its role in comorbidities associated with diabetes in STZ-nicotinamide induced
diabetic rats. Male albino Wistar rats were divided into control, diabetic
control, glimepiride treated (10 mg/kg), and diabetic rats treated with 250, 500,
and 1000 mg/kg dose of AEATP groups and fasting blood glucose, glycated
hemoglobin, total cholesterol, triglyceride, LDL, VLDL, HDL, SGOT, and SGPT
levels were measured. STZ significantly increased fasting blood glucose level,
glycated hemoglobin, total cholesterol, triglyceride, LDL, VLDL, SGOT, and SGPT
levels, whereas HDL level was reduced as compared to control group. After 7 days
of administration, 500 and 1000 mg/kg dose of AEATP showed significant reduction
(P < 0.05) in fasting blood glucose level compared to diabetic control. AEATP has
also reduced total cholesterol, triglyceride, LDL, VLDL, SGOT, and SGPT levels
and improved HDL level as compared to diabetic control group. Our study is the
first to report the normalization of fasting blood glucose level, lipid profile,
and liver enzyme in AEATP treated diabetic rats. Thus, it can be concluded that
AEATP may have potentials for the treatment of T2DM and its comorbidities.
PMID- 25121105
TI - Local packing density is the main structural determinant of the rate of protein
sequence evolution at site level.
AB - Functional and biophysical constraints result in site-dependent patterns of
protein sequence variability. It is commonly assumed that the key structural
determinant of site-specific rates of evolution is the Relative Solvent
Accessibility (RSA). However, a recent study found that amino acid substitution
rates correlate better with two Local Packing Density (LPD) measures, the
Weighted Contact Number (WCN) and the Contact Number (CN), than with RSA. This
work aims at a more thorough assessment. To this end, in addition to substitution
rates, we considered four other sequence variability scores, four measures of
solvent accessibility (SA), and other CN measures. We compared all properties for
each protein of a structurally and functionally diverse representative dataset of
monomeric enzymes. We show that the best sequence variability measures take into
account phylogenetic tree topology. More importantly, we show that both LPD
measures (WCN and CN) correlate better than all of the SA measures, regardless of
the sequence variability score used. Moreover, the independent contribution of
the best LPD measure is approximately four times larger than that of the best SA
measure. This study strongly supports the conclusion that a site's packing
density rather than its solvent accessibility is the main structural determinant
of its rate of evolution.
PMID- 25121106
TI - Rho/ROCK signal cascade mediates asymmetric dimethylarginine-induced vascular
smooth muscle cells migration and phenotype change.
AB - Asymmetric dimethylarginine (ADMA) induces vascular smooth muscle cells (VSMCs)
migration. VSMC phenotype change is a prerequisite of migration. RhoA and Rho
kinase (ROCK) mediate migration of VSMCs. We hypothesize that ADMA induces VSMC
migration via the activation of Rho/ROCK signal pathway and due to VSMCs
phenotype change. ADMA activates Rho/ROCK signal pathway that interpreted by the
elevation of RhoA activity and phosphorylation level of a ROCK substrate.
Pretreatment with ROCK inhibitor, Y27632 completely reverses the induction of
ADMA on ROCK and in turn inhibits ADMA-induced VSMCs migration. When the Rho/ROCK
signal pathway has been blocked by pretreatment with Y27632, the induction of ERK
signal pathway by ADMA is completely abrogated. Elimination of ADMA via
overexpression of dimethylarginine dimethylaminohydrolase 2 (DDAH2) and L
arginine both blocks the effects of ADMA on the activation of Rho/ROCK and extra
cellular signal-regulated kinase (ERK) in VSMCs. The expression of differentiated
phenotype relative proteins was reduced and the actin cytoskeleton was
disassembled by ADMA, which were blocked by Y27632, further interpreting that
ADMA inducing VSMCs migration via Rho/ROCK signal pathway is due to its effect on
the VSMCs phenotype change. Our present study may help to provide novel insights
into the therapy and prevention of atherosclerosis.
PMID- 25121108
TI - Particle-size distribution models for the conversion of Chinese data to FAO/USDA
system.
AB - We investigated eleven particle-size distribution (PSD) models to determine the
appropriate models for describing the PSDs of 16349 Chinese soil samples. These
data are based on three soil texture classification schemes, including one ISSS
(International Society of Soil Science) scheme with four data points and two
Katschinski's schemes with five and six data points, respectively. The adjusted
coefficient of determination r (2), Akaike's information criterion (AIC), and
geometric mean error ratio (GMER) were used to evaluate the model performance.
The soil data were converted to the USDA (United States Department of
Agriculture) standard using PSD models and the fractal concept. The performance
of PSD models was affected by soil texture and classification of fraction
schemes. The performance of PSD models also varied with clay content of soils.
The Anderson, Fredlund, modified logistic growth, Skaggs, and Weilbull models
were the best.
PMID- 25121109
TI - A synchronous-asynchronous particle swarm optimisation algorithm.
AB - In the original particle swarm optimisation (PSO) algorithm, the particles'
velocities and positions are updated after the whole swarm performance is
evaluated. This algorithm is also known as synchronous PSO (S-PSO). The strength
of this update method is in the exploitation of the information. Asynchronous
update PSO (A-PSO) has been proposed as an alternative to S-PSO. A particle in A
PSO updates its velocity and position as soon as its own performance has been
evaluated. Hence, particles are updated using partial information, leading to
stronger exploration. In this paper, we attempt to improve PSO by merging both
update methods to utilise the strengths of both methods. The proposed synchronous
asynchronous PSO (SA-PSO) algorithm divides the particles into smaller groups.
The best member of a group and the swarm's best are chosen to lead the search.
Members within a group are updated synchronously, while the groups themselves are
asynchronously updated. Five well-known unimodal functions, four multimodal
functions, and a real world optimisation problem are used to study the
performance of SA-PSO, which is compared with the performances of S-PSO and A
PSO. The results are statistically analysed and show that the proposed SA-PSO has
performed consistently well.
PMID- 25121107
TI - Beneficial effects of adiponectin on periodontal ligament cells under normal and
regenerative conditions.
AB - Type 2 diabetes and obesity are increasing worldwide and linked to periodontitis,
a chronic disease which is characterized by the irreversible destruction of the
tooth-supporting tissues, that is, periodontium. The mechanisms underlying the
association of diabetes mellitus and obesity with periodontal destruction and
compromised periodontal healing are not well understood, but decreased plasma
levels of adiponectin, as found in diabetic and obese individuals, might be a
critical mechanistic link. The aim of this in vitro study was to examine the
effects of adiponectin on periodontal ligament (PDL) cells under normal and
regenerative conditions, and to study the regulation of adiponectin and its
receptors in these cells. Adiponectin stimulated significantly the expression of
growth factors and extracellular matrix, proliferation, and in vitro wound
healing, reduced significantly the constitutive tumor necrosis factor-alpha
expression, and caused a significant upregulation of its own expression. The
beneficial actions of enamel matrix derivative on a number of PDL cell functions
critical for periodontal regeneration were partially enhanced by adiponectin. The
periodontopathogen Porphyromonas gingivalis inhibited the adiponectin expression
and stimulated the expression of its receptors. In conclusion, reduced levels of
adiponectin, as found in type 2 diabetes and obesity, may compromise periodontal
health and healing.
PMID- 25121110
TI - Rhizomes help the forage grass Leymus chinensis to adapt to the salt and alkali
stresses.
AB - Leymus chinensis has extensive ecological adaptability and can grow well in
saline-alkaline soils. The knowledge about tolerance mechanisms of L. chinensis
could be base for utilization of saline-alkaline soils and grassland restoration
and rebuilding. Two neutral salts (NaCl : Na2SO4 = 9 : 1) and two alkaline salts
(NaHCO3 : Na2CO3 = 9 : 1) with concentration of 0, 100, and 200 mmol/L were used
to treat potted 35-day-old seedlings with rhizome growth, respectively. After 10
days, the biomass and number of daughter shoots all decreased, with more
reduction in alkali than in salt stress. The rhizome biomass reduced more than
other organs. The number of daughter shoots from rhizome was more than from
tillers. Under both stresses, Na(+) contents increased more in rhizome than in
other organs; the reduction of K(+) content was more in underground than aerial
tissue. Anion ions or organic acids were absorbed to neutralize cations. Na(+)
content in stem and leaf increased markedly in high alkalinity (200 mmol/L), with
accumulation of soluble sugar and organic acids sharply. Rhizomes help L.
chinensis to adapt to saline and low alkaline stresses by transferring Na(+).
However, rhizomes lost the ability to prevent Na(+) transport to aerial organs
under high alkalinity, which led to severe growth inhibition of L. chinensis.
PMID- 25121111
TI - Integrated navigation fusion strategy of INS/UWB for indoor carrier attitude
angle and position synchronous tracking.
AB - In some GPS failure conditions, positioning for mobile target is difficult. This
paper proposed a new method based on INS/UWB for attitude angle and position
synchronous tracking of indoor carrier. Firstly, error model of INS/UWB
integrated system is built, including error equation of INS and UWB. And combined
filtering model of INS/UWB is researched. Simulation results show that the two
subsystems are complementary. Secondly, integrated navigation data fusion
strategy of INS/UWB based on Kalman filtering theory is proposed. Simulation
results show that FAKF method is better than the conventional Kalman filtering.
Finally, an indoor experiment platform is established to verify the integrated
navigation theory of INS/UWB, which is geared to the needs of coal mine working
environment. Static and dynamic positioning results show that the INS/UWB
integrated navigation system is stable and real-time, positioning precision meets
the requirements of working condition and is better than any independent
subsystem.
PMID- 25121112
TI - The smallest spectral radius of graphs with a given clique number.
AB - The first four smallest values of the spectral radius among all connected graphs
with maximum clique size omega >= 2 are obtained.
PMID- 25121113
TI - Long-term and short-term effects of hemodialysis on liver function evaluated
using the galactose single-point test.
AB - AIM: The galactose single-point (GSP) test assesses functioning liver mass by
measuring the galactose concentration in the blood 1 hour after its
administration. The purpose of this study was to investigate the impact of
hemodialysis (HD) on short-term and long-term liver function by use of GSP test.
METHODS: Seventy-four patients on maintenance HD (46 males and 28 females, 60.38
+/- 11.86 years) with a mean time on HD of 60.77 +/- 48.31 months were studied.
The GSP values were compared in two groups: (1) before and after single session
HD, and (2) after one year of maintenance HD. RESULTS: Among the 74 HD patient,
only the post-HD Cr levels and years on dialysis were significantly correlated
with GSP values (r = 0.280, P < 0.05 and r = -0.240, P < 0.05, resp.). 14 of 74
patients were selected for GSP evaluation before and after a single HD session,
and the hepatic clearance of galactose was similar (pre-HD 410 +/- 254 g/mL, post
HD 439 +/- 298 g/mL, P = 0.49). GSP values decreased from 420.20 +/- 175.26 g/mL
to 383.40 +/- 153.97 g/mL after 1 year maintenance HD in other 15 patients (mean
difference: 19.00 +/- 37.66 g/mL, P < 0.05). CONCLUSIONS: Patients on maintenance
HD for several years may experience improvement of their liver function. However,
a single HD session does not affect liver function significantly as assessed by
the GSP test. Since the metabolism of galactose is dependent on liver blood flow
and hepatic functional mass, further studies are needed.
PMID- 25121114
TI - Towards dynamic remote data auditing in computational clouds.
AB - Cloud computing is a significant shift of computational paradigm where computing
as a utility and storing data remotely have a great potential. Enterprise and
businesses are now more interested in outsourcing their data to the cloud to
lessen the burden of local data storage and maintenance. However, the outsourced
data and the computation outcomes are not continuously trustworthy due to the
lack of control and physical possession of the data owners. To better streamline
this issue, researchers have now focused on designing remote data auditing (RDA)
techniques. The majority of these techniques, however, are only applicable for
static archive data and are not subject to audit the dynamically updated
outsourced data. We propose an effectual RDA technique based on algebraic
signature properties for cloud storage system and also present a new data
structure capable of efficiently supporting dynamic data operations like append,
insert, modify, and delete. Moreover, this data structure empowers our method to
be applicable for large-scale data with minimum computation cost. The comparative
analysis with the state-of-the-art RDA schemes shows that the proposed scheme is
secure and highly efficient in terms of the computation and communication
overhead on the auditor and server.
PMID- 25121115
TI - Displacement-based back-analysis of the model parameters of the Nuozhadu high
earth-rockfill dam.
AB - The parameters of the constitutive model, the creep model, and the wetting model
of materials of the Nuozhadu high earth-rockfill dam were back-analyzed together
based on field monitoring displacement data by employing an intelligent back
analysis method. In this method, an artificial neural network is used as a
substitute for time-consuming finite element analysis, and an evolutionary
algorithm is applied for both network training and parameter optimization. To
avoid simultaneous back-analysis of many parameters, the model parameters of the
three main dam materials are decoupled and back-analyzed separately in a
particular order. Displacement back-analyses were performed at different stages
of the construction period, with and without considering the creep and wetting
deformations. Good agreement between the numerical results and the monitoring
data was obtained for most observation points, which implies that the back
analysis method and decoupling method are effective for solving complex problems
with multiple models and parameters. The comparison of calculation results based
on different sets of back-analyzed model parameters indicates the necessity of
taking the effects of creep and wetting into consideration in the numerical
analyses of high earth-rockfill dams. With the resulting model parameters, the
stress and deformation distributions at completion are predicted and analyzed.
PMID- 25121116
TI - Narrow band region-based active contours model for noisy color image
segmentation.
AB - A narrow band active contour model for color image segmentation is proposed,
which applies local statistics to improve the robustness against noise. The crux
of our approach is to use intensity mean of local region to define the force
function within a level set framework, within which a narrow band is implemented
to further improve the computational efficiency. In addition, the image is
segmented from channel-to-channel, which shows superior performance when the
intensities of the object and background are similar. Furthermore, a multichannel
segmentation combination method is used to integrate the information of multiple
level sets. The proposed model has been applied to both synthetic and real images
with expected results, and the comparison with the state-of-the-art approaches
demonstrates the accuracy and superiority of our approach.
PMID- 25121117
TI - Haematological and biochemical parameters during the laying period in common
pheasant hens housed in enhanced cages.
AB - The development of selected haematological and biochemical parameters during the
laying period was monitored in common pheasant hens housed in an enhanced cage
system. The cages were enhanced by the addition of two perches and a shelter
formed by strips of cloth hanging in the corner of the cage. The results showed
significant changes in the haematological and biochemical parameters monitored
during egg laying. At the time when laying capacity approached a maximum, a
decrease was observed (P < 0.05) in haematocrit, erythrocytes, and haemoglobin
values, whereas monocytes, eosinophils, the heterophil/lymphocyte ratio,
phosphorus, and calcium exhibited an increase (P < 0.05). At the end of the
laying period, an increase (P < 0.05) was recorded in the count of leukocytes,
heterophils, lymphocytes and basophils, the heterophil to lymphocyte ratio, and
the concentrations of aspartate aminotransferase, cholesterol, phosphorus, and
calcium, whereas lower values (P < 0.05) were recorded for haematocrit and plasma
total protein in comparison with the values of the indicators at the beginning of
the laying period. The results provide new information about dynamic changes in
selected haematological and biochemical parameters in clinically healthy common
pheasant hens during the laying period.
PMID- 25121118
TI - Intrastrain comparison of the chemical composition and antioxidant activity of an
edible mushroom, Pleurotus giganteus, and its potent neuritogenic properties.
AB - Two strains of Pleurotus giganteus (commercial and wild) were tested for their
ability to induce neurite outgrowth in rat pheochromocytoma (PC12) and mouse
neuroblastoma-2a (N2a) cells. Treatment with the mushroom extracts resulted in
neuronal differentiation and neuronal elongation, but not nerve growth factor
(NGF) production. Linoleic acid (4.5-5.0%, w/w) which is a major fatty acid
present in the ethanol extract promoted NGF biosynthesis when augmented with low
concentration of NGF (5 ng/mL). The two strains of mushroom were found to be high
in protein (154-192 g kg(-1)), total polysaccharides, phenolics, and flavonoids
as well as vitamins B1, B2, and B3. The total phenolics present in the mushroom
extracts were positively correlated to the antioxidant activity (free radical
scavenging, ferric reducing power, and lipid peroxidation inhibition). To
conclude, P. giganteus could potentially be used in well-balanced diet and as a
source of dietary antioxidant to promote neuronal health.
PMID- 25121119
TI - Automated detection and evaluation of swallowing using a combined
EMG/bioimpedance measurement system.
AB - INTRODUCTION: Developing an automated diagnostic and therapeutic instrument for
treating swallowing disorders requires procedures able to reliably detect and
evaluate a swallow. We tested a two-stage detection procedure based on a combined
electromyography/bioimpedance (EMBI) measurement system. EMBI is able to detect
swallows and distinguish them from similar movements in healthy test subjects.
STUDY DESIGN: The study was planned and conducted as a case-control study (EA
1/019/10, and EA1/160/09, EA1/161/09). METHOD: The study looked at differences in
swallowing parameters in general and in the event of penetration during swallows
in healthy subjects and in patients with an oropharyngeal swallowing disorder. A
two-stage automated swallow detection procedure which used electromyography (EMG)
and bioimpedance (BI) to reliably detect swallows was developed. RESULTS:
Statistically significant differences between healthy subjects and patients with
a swallowing disorder were found in swallowing parameters previously used to
distinguish between swallowing and head movements. Our two-stage algorithm was
able to reliably detect swallows (sensitivity = 96.1%, specificity = 97.1%) on
the basis of these differences. DISCUSSION: Using a two-stage detection
procedure, the EMBI measurement procedure is able to detect and evaluate swallows
automatically and reliably. The two procedures (EMBI + swallow detection) could
in future form the basis for automated diagnosis and treatment (stimulation) of
swallowing disorders.
PMID- 25121121
TI - Mechanical performance and parameter sensitivity analysis of 3D braided
composites joints.
AB - 3D braided composite joints are the important components in CFRP truss, which
have significant influence on the reliability and lightweight of structures. To
investigate the mechanical performance of 3D braided composite joints, a
numerical method based on the microscopic mechanics is put forward, the modeling
technologies, including the material constants selection, element type, grid
size, and the boundary conditions, are discussed in detail. Secondly, a method
for determination of ultimate bearing capacity is established, which can consider
the strength failure. Finally, the effect of load parameters, geometric
parameters, and process parameters on the ultimate bearing capacity of joints is
analyzed by the global sensitivity analysis method. The results show that the
main pipe diameter thickness ratio gamma, the main pipe diameter D, and the
braided angle alpha are sensitive to the ultimate bearing capacity N.
PMID- 25121120
TI - Estimating body related soft biometric traits in video frames.
AB - Soft biometrics can be used as a prescreening filter, either by using single
trait or by combining several traits to aid the performance of recognition
systems in an unobtrusive way. In many practical visual surveillance scenarios,
facial information becomes difficult to be effectively constructed due to several
varying challenges. However, from distance the visual appearance of an object can
be efficiently inferred, thereby providing the possibility of estimating body
related information. This paper presents an approach for estimating body related
soft biometrics; specifically we propose a new approach based on body measurement
and artificial neural network for predicting body weight of subjects and
incorporate the existing technique on single view metrology for height estimation
in videos with low frame rate. Our evaluation on 1120 frame sets of 80 subjects
from a newly compiled dataset shows that the mentioned soft biometric information
of human subjects can be adequately predicted from set of frames.
PMID- 25121123
TI - A lower bound on the sinc function and its application.
AB - A lower bound on the sinc function is given. Application for the sequence
{b(n)}(n=1)(infinity) which related to Carleman inequality is given as well.
PMID- 25121122
TI - Observer design for a core circadian rhythm network.
AB - The paper investigates the observer design for a core circadian rhythm network in
Drosophila and Neurospora. Based on the constructed highly nonlinear differential
equation model and the recently proposed graphical approach, we design a rather
simple observer for the circadian rhythm oscillator, which can well track the
state of the original system for various input signals. Numerical simulations
show the effectiveness of the designed observer. Potential applications of the
related investigations include the real-world control and experimental design of
the related biological networks.
PMID- 25121124
TI - Electronically tunable quadrature oscillator using grounded components with
current and voltage outputs.
AB - The electronically tunable quadrature oscillator using a single multiple-output
current controlled current differencing transconductance amplifier (MO-CCCDTA)
and grounded passive components is presented. The proposed configuration uses a
single MO-CCCDTA, two grounded capacitors and one grounded resistor. Two high
output impedance quadrature current signals and two quadrature voltage signals
with 90 degrees phase difference. The oscillation condition and oscillation
frequency of the proposed quadrature oscillator are independently controllable.
The use of only grounded passive components makes the proposed circuit ideal for
integrated circuit implementation.
PMID- 25121125
TI - Vehicle density based forwarding protocol for safety message broadcast in VANET.
AB - In vehicular ad hoc networks (VANETs), the medium access control (MAC) protocol
is of great importance to provide time-critical safety applications. Contemporary
multihop broadcast protocols in VANETs usually choose the farthest node in
broadcast range as the forwarder to reduce the number of forwarding hops.
However, in this paper, we demonstrate that the farthest forwarder may experience
large contention delay in case of high vehicle density. We propose an IEEE 802.11
based multihop broadcast protocol VDF to address the issue of emergency message
dissemination. To achieve the tradeoff between contention delay and forwarding
hops, VDF adaptably chooses the forwarder according to the vehicle density.
Simulation results show that, due to its ability to decrease the transmission
collisions, the proposed protocol can provide significantly lower broadcast
delay.
PMID- 25121126
TI - Applying dynamic priority scheduling scheme to static systems of pinwheel task
model in power-aware scheduling.
AB - Power-aware scheduling reduces CPU energy consumption in hard real-time systems
through dynamic voltage scaling (DVS). In this paper, we deal with pinwheel task
model which is known as static and predictable task model and could be applied to
various embedded or ubiquitous systems. In pinwheel task model, each task's
priority is static and its execution sequence could be predetermined. There have
been many static approaches to power-aware scheduling in pinwheel task model.
But, in this paper, we will show that the dynamic priority scheduling results in
power-aware scheduling could be applied to pinwheel task model. This method is
more effective than adopting the previous static priority scheduling methods in
saving energy consumption and, for the system being still static, it is more
tractable and applicable to small sized embedded or ubiquitous computing. Also,
we introduce a novel power-aware scheduling algorithm which exploits all slacks
under preemptive earliest-deadline first scheduling which is optimal in
uniprocessor system. The dynamic priority method presented in this paper could be
applied directly to static systems of pinwheel task model. The simulation results
show that the proposed algorithm with the algorithmic complexity of O(n) reduces
the energy consumption by 10-80% over the existing algorithms.
PMID- 25121127
TI - Locked mouths: Tooth loss in a women's prison in northeastern Brazil.
AB - BACKGROUND: Prisoners, in general, exhibit unsatisfactory oral conditions,
especially with regard to the large number of missing teeth and with untreated
caries. The aim of this study was to assess tooth loss, use of and need for
prosthetic rehabilitation, and use of dental services among inmates. A cross
sectional study involving 65 inmates was developed at the Regional Women's Prison
of Campina Grande, Brazil. Data regarding sociodemographic and sentencing
profile, use of dental services, dental morbidity, and self-perceived oral health
impacts were investigated. Chi-square, Pearson, and Kruskal-Wallis (P < 0.05)
statistical tests were used. The mean tooth loss was 11.3 teeth. Significant
association between tooth loss and oral health satisfaction (P = 0.049), self
perceived need for dental prosthesis (P < 0.001), uncomfortable teeth brushing (P
= 0.005), difficult speaking (P = 0.002), and difficulty in performing routine
tasks (P = 0.025) was observed. It was observed that 29.2% of inmates were using
some type of prosthesis, all deemed unsuitable for use, and 78.5% of inmates
needed prosthetic rehabilitation. The oral health condition of the population
studied was found to be poor, and prisoners showed significant tooth loss and
need for dentures, with the aggravation of having tooth extraction as the major
reason for seeking dental care.
PMID- 25121128
TI - Train repathing in emergencies based on fuzzy linear programming.
AB - Train pathing is a typical problem which is to assign the train trips on the sets
of rail segments, such as rail tracks and links. This paper focuses on the train
pathing problem, determining the paths of the train trips in emergencies. We
analyze the influencing factors of train pathing, such as transferring cost,
running cost, and social adverse effect cost. With the overall consideration of
the segment and station capability constraints, we build the fuzzy linear
programming model to solve the train pathing problem. We design the fuzzy
membership function to describe the fuzzy coefficients. Furthermore, the
contraction-expansion factors are introduced to contract or expand the value
ranges of the fuzzy coefficients, coping with the uncertainty of the value range
of the fuzzy coefficients. We propose a method based on triangular fuzzy
coefficient and transfer the train pathing (fuzzy linear programming model) to a
determinate linear model to solve the fuzzy linear programming problem. An
emergency is supposed based on the real data of the Beijing-Shanghai Railway. The
model in this paper was solved and the computation results prove the availability
of the model and efficiency of the algorithm.
PMID- 25121129
TI - A note on parametric surfaces in Minkowski 3-space.
AB - With the help of the Frenet frame of a given pseudo null curve, a family of
parametric surfaces is expressed as a linear combination of this frame. The
necessary and sufficient conditions are examined for that curve to be an
isoparametric and asymptotic on the parametric surface. It is shown that there is
not any cylindrical and developable ruled surface as a parametric surface. Also,
some interesting examples are illustrated about these surfaces.
PMID- 25121130
TI - Gender dysphoria: the role of sex reassignment surgery.
PMID- 25121132
TI - Reconfigurable ring filter with controllable frequency response.
AB - Reconfigurable ring filter based on single-side-access ring topology is
presented. Using capacitive tuning elements, the electrical length of the ring
can be manipulated to shift the nominal center frequency to a desired position. A
synthesis is developed to determine the values of the capacitive elements. To
show the advantage of the synthesis, it is applied to the reconfigurable filter
design using RF lumped capacitors. The concept is further explored by introducing
varactor-diodes to continuously tune the center frequency of the ring filter. For
demonstration, two prototypes of reconfigurable ring filters are realized using
microstrip technology, simulated, and measured to validate the proposed concept.
The reconfigured filter using lumped elements is successfully reconfigured from 2
GHz to 984.4 MHz and miniaturized by 71% compared to the filter directly designed
at the same reconfigured frequency, while, for the filter using varactor-diodes,
the frequency is chosen from 1.10 GHz to 1.38 GHz spreading over 280 MHz
frequency range. Both designs are found to be compact with acceptable insertion
loss and high selectivity.
PMID- 25121131
TI - Sequence variants of ADIPOQ and association with type 2 diabetes mellitus in
Taiwan Chinese Han population.
AB - Diabetes is a serious global health problem. Large-scale genome-wide association
studies identified loci for type 2 diabetes mellitus (T2DM), including
adiponectin (ADIPOQ) gene and transcription factor 7-like 2 (TCF7L2), but few
studies clarified the effect of genetic polymorphisms of ADIPOQ and TCF7L2 on
risk of T2DM. We attempted to elucidate association between T2DM and polymorphic
variations of both in Taiwan's Chinese Han population, with our retrospective
case-control study genotyping single nucleotide polymorphisms (SNPs) in ADIPOQ
and TCF7L2 genes both in 149 T2DM patients and in 139 healthy controls from
Taiwan. Statistical analysis gauged association of these polymorphisms with risk
of T2DM to show ADIPOQ rs1501299 polymorphism variations strongly correlated with
T2DM risk (P = 0.042), with rs2241766 polymorphism being not associated with T2DM
(P = 0.967). However, both polymorphisms rs7903146 and rs12255372 of TCF7L2 were
rarely detected in Taiwanese people. This study avers that ADIPOQ rs1501299
polymorphism contributes to risk of T2DM in the Taiwanese population.
PMID- 25121134
TI - Damage assessment of two-way bending RC slabs subjected to blast loadings.
AB - Terrorist attacks on vulnerable structures and their individual structural
members may cause considerable damage and loss of life. However, the research
work on response and damage analysis of single structural components, for
example, a slab to blast loadings, is limited in the literature and this is
necessary for assessing its vulnerability. This study investigates the blast
response and damage assessment of a two-way bending reinforced concrete (RC) slab
subjected to blast loadings. Numerical modeling and analysis are carried out
using the commercial finite element code LS-DYNA 971. A damage assessment
criterion for the two-way bending RC slab is defined based on the original and
residual uniformly distributed load-carrying capacity. Parametric studies are
carried out to investigate the effects of explosive weight and explosive position
on the damage mode of the two-way RC slab. Some design parameters, such as the
boundary conditions and the negative reinforcement steel bar length, are also
discussed. The illustrated results show that the proposed criterion can apply to
all failure modes. The damage assessment results are more accurate than the ones
due to the conventional deformation criterion.
PMID- 25121133
TI - On the open problem related to rank equalities for the sum of finitely many
idempotent matrices and its applications.
AB - Tian and Styan have shown many rank equalities for the sum of two and three
idempotent matrices and pointed out that rank equalities for the sum P1 + ?+P k
with P1,..., P k be idempotent (k > 3) are still open. In this paper, by using
block Gaussian elimination, we obtained rank equalities for the sum of finitely
many idempotent matrices and then solved the open problem mentioned above.
Extensions to scalar-potent matrices and some related matrices are also included.
PMID- 25121135
TI - Efficient and scalable graph similarity joins in MapReduce.
AB - Along with the emergence of massive graph-modeled data, it is of great importance
to investigate graph similarity joins due to their wide applications for multiple
purposes, including data cleaning, and near duplicate detection. This paper
considers graph similarity joins with edit distance constraints, which return
pairs of graphs such that their edit distances are no larger than a given
threshold. Leveraging the MapReduce programming model, we propose MGSJoin, a
scalable algorithm following the filtering-verification framework for efficient
graph similarity joins. It relies on counting overlapping graph signatures for
filtering out nonpromising candidates. With the potential issue of too many key
value pairs in the filtering phase, spectral Bloom filters are introduced to
reduce the number of key-value pairs. Furthermore, we integrate the multiway join
strategy to boost the verification, where a MapReduce-based method is proposed
for GED calculation. The superior efficiency and scalability of the proposed
algorithms are demonstrated by extensive experimental results.
PMID- 25121136
TI - Stochastic optimized relevance feedback particle swarm optimization for content
based image retrieval.
AB - One of the major challenges for the CBIR is to bridge the gap between low level
features and high level semantics according to the need of the user. To overcome
this gap, relevance feedback (RF) coupled with support vector machine (SVM) has
been applied successfully. However, when the feedback sample is small, the
performance of the SVM based RF is often poor. To improve the performance of RF,
this paper has proposed a new technique, namely, PSO-SVM-RF, which combines SVM
based RF with particle swarm optimization (PSO). The aims of this proposed
technique are to enhance the performance of SVM based RF and also to minimize the
user interaction with the system by minimizing the RF number. The PSO-SVM-RF was
tested on the coral photo gallery containing 10908 images. The results obtained
from the experiments showed that the proposed PSO-SVM-RF achieved 100% accuracy
in 8 feedback iterations for top 10 retrievals and 80% accuracy in 6 iterations
for 100 top retrievals. This implies that with PSO-SVM-RF technique high accuracy
rate is achieved at a small number of iterations.
PMID- 25121137
TI - Generalized equilibrium problem with mixed relaxed monotonicity.
AB - We extend the concept of relaxed alpha-monotonicity to mixed relaxed alpha-beta
monotonicity. The concept of mixed relaxed alpha-beta-monotonicity is more
general than many existing concepts of monotonicities. Finally, we apply this
concept and well known KKM-theory to obtain the solution of generalized
equilibrium problem.
PMID- 25121138
TI - Thermal cycling life prediction of Sn-3.0Ag-0.5Cu solder joint using type-I
censored data.
AB - Because solder joint interconnections are the weaknesses of microelectronic
packaging, their reliability has great influence on the reliability of the entire
packaging structure. Based on an accelerated life test the reliability assessment
and life prediction of lead-free solder joints using Weibull distribution are
investigated. The type-I interval censored lifetime data were collected from a
thermal cycling test, which was implemented on microelectronic packaging with
lead-free ball grid array (BGA) and fine-pitch ball grid array (FBGA)
interconnection structures. The number of cycles to failure of lead-free solder
joints is predicted by using a modified Engelmaier fatigue life model and a type
I censored data processing method. Then, the Pan model is employed to calculate
the acceleration factor of this test. A comparison of life predictions between
the proposed method and the ones calculated directly by Matlab and Minitab is
conducted to demonstrate the practicability and effectiveness of the proposed
method. At last, failure analysis and microstructure evolution of lead-free
solders are carried out to provide useful guidance for the regular maintenance,
replacement of substructure, and subsequent processing of electronic products.
PMID- 25121139
TI - Outlier detection method in linear regression based on sum of arithmetic
progression.
AB - We introduce a new nonparametric outlier detection method for linear series,
which requires no missing or removed data imputation. For an arithmetic
progression (a series without outliers) with n elements, the ratio (R) of the sum
of the minimum and the maximum elements and the sum of all elements is always 2/n
: (0,1]. R ? 2/n always implies the existence of outliers. Usually, R < 2/n
implies that the minimum is an outlier, and R > 2/n implies that the maximum is
an outlier. Based upon this, we derived a new method for identifying significant
and nonsignificant outliers, separately. Two different techniques were used to
manage missing data and removed outliers: (1) recalculate the terms after (or
before) the removed or missing element while maintaining the initial angle in
relation to a certain point or (2) transform data into a constant value, which is
not affected by missing or removed elements. With a reference element, which was
not an outlier, the method detected all outliers from data sets with 6 to 1000
elements containing 50% outliers which deviated by a factor of +/-1.0e - 2 to +/
1.0e + 2 from the correct value.
PMID- 25121140
TI - Uplifting behavior of shallow buried pipe in liquefiable soil by dynamic
centrifuge test.
AB - Underground pipelines are widely applied in the so-called lifeline engineerings.
It shows according to seismic surveys that the damage from soil liquefaction to
underground pipelines was the most serious, whose failures were mainly in the
form of pipeline uplifting. In the present study, dynamic centrifuge model tests
were conducted to study the uplifting behaviors of shallow-buried pipeline
subjected to seismic vibration in liquefied sites. The uplifting mechanism was
discussed through the responses of the pore water pressure and earth pressure
around the pipeline. Additionally, the analysis of force, which the pipeline was
subjected to before and during vibration, was introduced and proved to be
reasonable by the comparison of the measured and the calculated results. The
uplifting behavior of pipe is the combination effects of multiple forces, and is
highly dependent on the excess pore pressure.
PMID- 25121142
TI - Plasmonic nanoparticle-film calipers for rapid and ultrasensitive dimensional and
refractometric detection.
AB - In this study, we develop an ultrasensitive nanoparticle (NP)-film caliper that
functions with high resolution (angstrom scale) in response to both the
dimensions and refractive index of the spacer sandwiched between the NPs and the
film. The anisotropy of the plasmonic gap mode in the NP-film caliper can be
characterized readily using spectroscopic ellipsometry (SE) without the need for
further optical modeling. To the best of our knowledge, this paper is the first
to report the use of SE to study the plasmonic gap modes in NP-film calipers and
to demonstrate that SE is a robust and convenient method for analyzing NP-film
calipers. The high sensitivity of this system originates from the plasmonic gap
mode in the NP-film caliper, induced by electromagnetic coupling between the NPs
and the film. The refractometric sensitivity of this NP-film caliper reaches up
to 314 nm per RIU, which is superior to those of other NP-based sensors. The NP
film caliper also provides high dimensional resolution, down to the angstrom
scale. In this study, the shift in wavelength in response to the change in gap
spacing is approximately 9 nm A(-1). Taking advantage of the ultrasensitivity of
this NP-film caliper, we develop a platform for discriminating among thiol
containing amino acids.
PMID- 25121141
TI - Working capital management, corporate performance, and strategic choices of the
wholesale and retail industry in China.
AB - We examine the influence of strategic choice on working capital configurations
and observe how the relationship between working capital ratio and operational
performance differs depending on strategy. By clustering the strategic factors of
the wholesale and retail industry, we find three categories of strategies:
terminal market strategy, middle market strategy, and hybrid strategy. Using the
panel data of the listed companies of the wholesale and retail industry as our
sample, we analyze the differences in the ways companies configure working
capital, the speed with which working capital adjusts to its target, and the
effects of working capital on performance for companies that make different
strategic choices. The empirical results suggest that working capital is
configured and adjusted to its target in different ways under different
competitive strategic choices. This effect is finally transferred to influence
the relationship between working capital configuration and operational
performance.
PMID- 25121143
TI - Choosing to avoid poor-quality healthcare.
PMID- 25121144
TI - Delta-9-tetrahydrocannabinol + cannabidiol. A reasonable option for some patients
with multiple sclerosis.
AB - Conventional drugs have only a limited impact on spasticity associated with
multiple sclerosis and are rarely satisfactory. A solution for oral transmucosal
delivery (spray) containing a mixture of cannabis extracts (2.7 mg of delta-9
tetrahydrocannabinol + 2.5 mg of cannabidiol per spray) has been granted
marketing authorisation in France for patients who are inadequately relieved by
standard treatments. Three double-blind, placebo-controlled trials in a total of
about 300 patients tested this combination, in addition to ongoing treatment, for
periods of 6 to 14 weeks. Individually, none of these trials showed any tangible
anti-spastic efficacy, but two combined analyses showed "response rates" of about
35% with the mixture versus about 25% with placebo. In a trial with 572 patients,
the 241 patients who "responded" after 4 weeks of treatment were randomised to
either continue using the cannabis extract or receive placebo. Twelve weeks
later, 75% of patients using the extract were still "responders", versus 51% of
patients switched to placebo. The principal adverse effects of the cannabis
extracts consist of neuropsychiatric disorders that resolve on treatment
withdrawal. The potential for abuse increases with the dose and is tangible from
16 sprays per day. Pharmacokinetic interactions due to P-glycoprotein inhibition
are likely. Treatment during pregnancy may lead to neonatal withdrawal symptoms.
In practice, about 10% of patients in whom standard anti-spastic medications are
unsatisfactory benefit from a specific effect of the cannabis extracts contained
in this oral spray.
PMID- 25121145
TI - INN common-stem nal.
PMID- 25121146
TI - Insulin degludec. Uncertainty over cardiovascular harms.
AB - Insulin isophane (NPH) is the standard long-acting human insulin for patients
with type 1 and type 2 diabetes. Long-acting human insulin analogues are also
available: insulin glargine and insulin detemir. Uncertainties remain concerning
their long-term adverse effects. Insulin degludec (Tresiba, Novo Nordisk) is
another long-acting human insulin analogue, also approved in the EU for patients
with type 1 and type 2 diabetes. It was authorised at a concentration of 100
units per ml, like other insulins, and also at a concentration of 200 units per
ml. There are no comparative data on insulin degludec 200 units per ml in
patients using high doses of insulin. Insulin degludec has mainly been evaluated
in ten randomised, unblinded, "non-inferiority" trials lasting 26 to 52 weeks,
nine versus insulin glargine and one versus insulin detemir. Insulin degludec was
administered at a fixed time each evening, or in either the morning or evening on
alternate days, at varying intervals of 8 to 40 hours between doses. Efficacy in
terms of HbA1c control was similar to that of the other insulin analogues
administered once a day. The frequency of severe hypoglycaemia was similar in the
groups treated with insulin degludec and those treated with the other insulins
(10% to 12% among patients with type 1 diabetes and less than 5% in patients with
type 2 diabetes). Deaths and other serious adverse events were similarly frequent
in the different groups. A meta-analysis of clinical trials, carried out by the
US Food and Drug Administration, suggested an increase of about 60% in the
incidence of cardiovascular complications, based on a composite endpoint
combining myocardial infarction, stroke and cardiovascular death. Other adverse
effects observed in these trials were already known to occur with human insulin
and its analogues, including weight gain, hypersensitivity reactions, reactions
at the injection site, etc. The trials were too short in duration to assess long
term harms, particularly cancer. Clinical experience with insulin degludec in
pregnant women is very limited. It is therefore best to avoid using this analogue
during pregnancy. In France, the concentration of all other insulins injected
with a syringe or prefilled pen is 100 units per ml. The new concentration of 200
units per ml contained in insulin degludec prefilled pens creates a risk of
confusion and overdose. In practice, there is already a relatively wide range of
options available for patients with type 1 or type 2 diabetes who require insulin
therapy. As insulin degludec has no proven advantages, it is better to avoid
using it, at least pending further data on the risk of cardiovascular events.
Insulin isophane remains the first-choice long-acting insulin, while insulin
glargine is most appropriate for some patients with type 1 diabetes.
PMID- 25121147
TI - Nalmefene. Alcohol dependence: no advance.
AB - Alcohol dependence is a chronic, severe and sometimes fatal disease.
Psychological and social support is a crucial element of patient management.
Acamprosate and naltrexone are the drugs of choice to help patients remain
abstinent, but they are only moderately effective. Nalmefene, an opioid receptor
antagonist related to naltrexone, has been authorised in the European Union to
help alcohol-dependent patients reduce their alcohol consumption. Nalmefene has
not been compared with naltrexone or acamprosate in clinical trials. Clinical
evaluation is mainly based on two double-blind, randomised, placebo-controlled
trials in which nalmefene was taken "on demand" at a dose of one tablet per day.
The trials lasted 6 months and included a total of 1322 patients. During an
initial two-week period in which all patients received medical and psychosocial
support, about one-third of patients in both trials reduced their alcohol
consumption without medication. Depending on the subgroup and the trial, about
one-third to one-half of patients discontinued medical treatment before the end
of the study period. In both trials, patients taking nalmefene had two fewer
"heavy drinking days" per month than patients in the placebo groups. However, at
the end of the study, they continued to drink heavily at least one week per month
on average. Daily alcohol consumption was 5 to 9 grams lower with nalmefene than
with placebo. The most frequent adverse effects observed in clinical trials were
insomnia, dizziness, headache and nausea, which were severe in more than 10% of
patients. Other serious but less frequent adverse effects included confusion,
hallucinations and dissociation, usually at the beginning of treatment. These
adverse effects affected about 3% of patients treated with nalmefene, a
proportion three times higher than in the placebo groups. The consequences of
mixing nalmefene with large amounts of alcohol are not known. In practice, the
effects of nalmefene in alcohol-dependent patients seeking to cut down or abstain
are of questionable clinical relevance. Adverse effects are frequent and less
well-determined than those of standard drugs. The impact of nalmefene on the
complications of alcohol dependence is not known. The crucial first step in the
management of alcohol-dependent patients is to establish a relationship built on
trust and to provide psychological and social support. When medication is
considered, it is better to choose acamprosate or naltrexone, drugs that are only
moderately effective but better-assessed.
PMID- 25121148
TI - Medication-induced violence others towards.
AB - Violent behaviour towards others is occasionally caused by drug therapy, through
sometimes complex and often poorly understood mechanisms. The consequences
described in detailed case reports can be serious, including homicide. Many
neuropsychotropic drugs can induce violent behaviour: smoking cessation drugs,
selective serotonin reuptake inhibitor antidepressants, amphetamines,
benzodiazepines and dopamine agonists. Some drugs not used as psychotropic agents
have also been implicated, for example: corticosteroids; anti-infective drugs
such as mefloquine, efavirenz, atazanavir, ribavirin and alfa interferons;
testosterone; and the asthma drug montelukast. The frequency of these adverse
effects cannot be reliably assessed using the data available. Only certain
reports mention a previous behaviour disorder. In practice, it is helpful to
inform patients if the drugs they are taking can provoke violent behaviour. It is
advisable to ask these patients about any behavioural changes and to encourage
them to inform members of their family or carers, to ensure that these changes
are identified and their consequences averted. In addition, remind them that
alcohol increases the risk.
PMID- 25121149
TI - Problems encountered in the pharmacovigilance of violence and aggression.
PMID- 25121150
TI - Alzheimer's disease in France: too many patients exposed to drug interactions
involving cholinesterase inhibitors.
AB - A study based on data from the French national health insurance system, for the
period 2003-2011, has shown that patients with Alzheimer's disease receiving a
cholinesterase inhibitor were exposed to another drug that reduces the heart rate
in about 44% of cases, a neuroleptic in 33% of cases, and an antimuscarinic for
urinary problems in 8% of cases. Drugs for Alzheimer's disease expose patients to
dangerous drug-drug interactions.
PMID- 25121151
TI - Capecitabine: toxic epidermal necrolysis and Stevens-Johnson syndrome.
PMID- 25121152
TI - Mefloquine: persistent vestibular disorders.
PMID- 25121153
TI - Contraceptive implants: pregnancies and problems with removal.
PMID- 25121154
TI - Antibiotic therapy for acute appendicitis in adults. Fewer immediate
complications than with surgery, but more subsequent failures.
AB - Appendectomy is the standard treatment for acute appendicitis. Since the 1990s,
antibiotic therapy has sometimes been proposed as an alternative to immediate
appendectomy. How effective are antibiotics in adults with uncomplicated acute
appendicitis, and what is the risk of complications? To answer these questions,
we conducted a review of the literature using the standard Prescrire methodology.
A systematic review with meta-analysis included four randomised trials of
antibiotics versus immediate appendectomy, in 900 patients hospitalised with
uncomplicated appendicitis. The studies included only patients with few severe
symptoms, thus undermining the strength of the results. Antibiotic therapy was
usually administered intravenously first, then orally. The antibiotics used were
amoxicillin + clavulanic acid, cefotaxime, or a fluoroquinolone. Metronidazole or
tinidazole was often added. The total duration of antibiotic treatment was 8 to
15 days. The overall incidence of complications of appendicitis (perforation,
peritonitis and surgical wound infections) was 25% in the immediate appendectomy
group versus 18% in the antibiotic group. The frequency of perforations and
peritonitis did not differ between the groups. All symptoms of appendicitis
disappeared, without relapse or rehospitalisation during the first month, in 78%
of patients in the antibiotic group. After one year of follow-up, 63% of patients
treated with antibiotics were asymptomatic and had no complications or
recurrences. In another systematic review of five randomised trials, outcome at
one year was optimal in 73% of patients treated with antibiotics alone versus 97%
of patients who had immediate appendectomy. In practice, in early 2014,
appendectomy remains the first-line treatment for uncomplicated acute
appendicitis. In some still poorly characterised patients, the harm-benefit
balance of antibiotic therapy is probably better than that of immediate
appendectomy. When informed of the risks, some patients are likely to choose
antibiotic therapy.
PMID- 25121155
TI - Towards better patient care: drugs to avoid in 2014.
AB - In order to help healthcare professionals and patients choose high-quality
treatments and avoid harms, we have updated our list of drugs to avoid in early
2014. Prescrire's assessments of the harm-benefit balance of new drugs and
indications are based on a rigorous procedure that includes a systematic and
reproducible literature search, identification of patient-relevant outcomes,
prioritisation of the supporting evidence, based on the strength of evidence,
comparison with standard treatments; and an analysis of both known and potential
adverse effects. Our 2014 review concerns drugs analysed in these pages over a
four-year period, from 2010 to 2013. We identified 68 drugs that are potentially
more harmful than beneficial in all of their authorised indications. In most
cases, other drugs with a better harm-benefit balance are available. In other
cases, there is no satisfactory alternative treatment. However, even for serious
diseases, this does not justify exposing patients to serious risks when a drug
has no proven efficacy. Some drugs can be used within the context of clinical
trials, as long as patients enrolled in such studies are informed that the harms
and benefits are uncertain and that this is precisely why they are being asked to
participate in clinical research. Tailored supportive care is the best option
when there are no available treatments capable of improving the prognosis, beyond
the placebo effect.
PMID- 25121156
TI - The finances of Association Mieux Prescrire: 2013 Prescrire annual report.
PMID- 25121157
TI - Anti-D prophylaxis: past, present and future.
AB - The new British Committee for Standards in Haematology (BCSH) guidelines for the
use of anti-D immunoglobulin in pregnancy provide a welcome clarification of the
use of anti-D in ectopic pregnancy and after red cell salvage during caesarean
section, of dosing with different preparations and distinguishing non-immune and
immune anti-D. The routine use of anti-D prophylaxis (RAADP) to prevent Rhesus
(Rh) D alloimmunisation during the third trimester is well established and
requires careful and well-audited local implementation to achieve the maximum
public health benefit. In the UK, such scrutiny may be provided by the reporting
of failed anti-D prophylaxis at women who have produced an immune anti-D that is
detectable for the first time in the current pregnancy through the voluntary
Serious Hazards of Transfusion reporting scheme (SHOT). Application of fetal RHD
genotyping would avoid giving anti-D to RhD negative women carrying an RhD
negative fetus. RAADP is directed by fetal RHD genotyping in some countries in
Northern Europe led by the Netherlands and Denmark. The economic case for RAADP
directed by fetal RHD genotyping needs to be carefully evaluated and in England
is under consideration by National Institute for Health and Clinical Excellence
(NICE). Possible future developments include the use of monoclonal anti-D
preparations, now in advanced clinical trials, and also testing the hypothesis
that directed RAADP from early in the second trimester may further reduce anti-D
immunisation.
PMID- 25121158
TI - BCSH guideline for the use of anti-D immunoglobulin for the prevention of
haemolytic disease of the fetus and newborn.
PMID- 25121159
TI - Baseline extracellular potassium level as an indicator of the rate of increase
of the same on further storage in CPDA-1 whole blood units: a potential approach
to complement FIFO system for prioritisation of blood bags for release from
blood-banks.
AB - BACKGROUND: Potassium levels in stored blood bags increases as they age.
Hyperkalemia in transfused blood has undesirable cardiac effects. MATERIALS AND
METHODS: Within a 19-month period, baseline and weekly samples from 15 CPDA-1
whole blood bags were collected till 28 days of storage and analysed for
potassium, sodium, uric acid, albumin and whole blood haemoglobin. RESULTS: One
unit increase in baseline (0 day) potassium in extracellular fluid of blood units
was associated with the following increases in potassium levels on later days of
storage: around two unit increase at 1 week (r2 = 0.50, P < 0.01) of storage;
four units increase at 2 weeks (r2 = 0.64, P < 0.001) and 3 weeks (r2 = 0.51, P <
0.01) of storage; six units at 4 weeks (r2 = 0.53, P < 0.01) of storage. Baseline
whole blood haemoglobin showed a moderate association with baseline potassium (r2
= 0.36, P < 0.05) and 2-week potassium (r2 = 0.35, P < 0.05) values. CONCLUSION:
For CPDA-1 blood bags (i) low baseline potassium blood bags might be preferred
for transfusion in cases demanding a low potassium load and (ii) coordinating the
'first-in-first-out' (FIFO) policy with 'early release of blood-bags with high
initial potassium' might be helpful in improving the release of suitable blood
units from blood-banks.
PMID- 25121160
TI - Transfusion of packed red blood cells reduces selenium levels and increases
lipid peroxidation in an in vivo ovine model.
AB - BACKGROUND: Oxidative stress from surgery or critically illness has been shown to
adversely contribute to morbidity and mortality. Recent studies record that
oxidative stress is heightened following packed red blood cell (PRBC)
transfusions and that products of oxidative stress accumulate as the PRBC ages.
However, there are no studies that investigate if transfusion of aged PRBC
actually increases the recipient's oxidative stress profile more than fresh PRBC.
OBJECTIVE: To compare the effect of fresh vs aged PRBC transfusions on the
recipient's oxidative stress using an ovine model. MATERIALS AND METHODS: Male
sheep were transfused with either fresh (n = 6) or aged (n = 6) ovine PRBC, and
serial blood samples taken. Plasma samples were analysed for lipid peroxidation
using the thiobarbituric acid reactive substances (TBARS) assay. This served as
an indicator of oxidative injury. Antioxidant function and trace element levels
were also measured. RESULTS: Like human PRBC, the ovine PRBC had negligible
selenium levels. Irrespective of age, PRBC transfusion was associated with
reduced selenium levels and antioxidant function, which correlated with increased
markers of lipid peroxidation. CONCLUSION: Transfusion of selenium poor PRBC can
dilute selenium levels and compromise glutathione peroxidase antioxidant activity
and thereby allow lipid peroxidation. As there was no evidence that aged PRBC
induced more severe oxidative injury this suggests that selenium dilution is a
key underlying mechanism. Further studies are needed to assess the impact of
transfusion-related oxidative stress in massive transfusions.
PMID- 25121161
TI - Job satisfaction, organisation commitment and retention in the public workforce:
a survey among pharmacists in Malaysia.
AB - OBJECTIVES: The aims of the study were to assess job satisfaction and
organisational commitment among pharmacists working in the public sector and its
influence on their likelihood to stay within the public workforce. METHODS: A
cross-sectional survey was conducted among all fully registered pharmacists
(FRPs) in the northern states of Malaysia in 2009 (n = 467). The questionnaire
consisted of three sections to capture the demographic characteristics of the
respondents, assess job satisfaction and organisational commitment of the
respondents and their likelihood of staying in public service. KEY FINDINGS: A
total of 247 FRPs (response rate 52.9%) in the northern region of Malaysia
participated in this survey. Majority of the respondents were women (n = 205,
83.0%), of Chinese ethnicity (n = 155, 62.8%), graduates from public universities
(n = 173, 70.0%), single (n = 172, 69.6%), with a median age of 27 years
(interquartile range (IQR) 2.0) and had worked with the Ministry of Health for a
median of 2.75 years (IQR 1.63). The mean job satisfaction and organisational
commitment score were 58.09 (standard deviation (SD) 11.83) and 53.46 (SD 6.65)
respectively out of a maximum possible score of 90. Majority of the respondents
claimed that they were likely to stay in public service (n = 176, 71.3%). Their
likelihood of staying in public service was affected by respondents' gender,
ethnicity, job satisfaction and organisational commitment. CONCLUSIONS: The
findings from this study provide stakeholders with evidence on factors and issues
affecting pharmacists' job satisfaction and commitment in the public workforce as
well as the likely turnover rate with an early cohort of pharmacists affected by
the compulsory service.
PMID- 25121163
TI - [Impact of tumor morcellation during the surgical extraction of solid tumors].
PMID- 25121164
TI - [CD74-NRG1: a new fusion gene in lung adenocarcinomas characterizing mucinous
adenocarcinomas].
PMID- 25121165
TI - What prescribing means to pharmacists: a qualitative exploration of practising
pharmacists in Alberta.
AB - OBJECTIVE: In 2007 Alberta, Canada, became the first North American jurisdiction
to adopt prescribing legislation for pharmacists. In light of these legislative
changes and expanded scope of pharmacy practice, we evaluated what 'prescribing'
means to pharmacists in Alberta and the application of prescribing in pharmacy
practice. METHODS: We invited pharmacists to participate in semi-structured
telephone interviews using closed and open-ended questions. Pharmacists working
in community, hospital or other settings were selected using a mix of random and
purposive sampling. Interviews were audiorecorded and transcribed, and data were
entered into nVIVO 9 software. Transcriptions were analysed by two investigators
using an interpretive description approach to identify themes. KEY FINDINGS:
Thirty-eight pharmacists were interviewed, of whom 13 had additional
(independent) prescribing authorization. Prescribing had a wide breadth of
meaning to the pharmacists in our study, which included writing a new
prescription and extending an existing prescription, as well as advising on non
prescription medications. Pharmacists described prescribing in terms of the
physical act of writing the prescription and as part of the patient care process
as well as the legislated definition of pharmacist prescribing. The sense of
increased responsibility associated with prescribing was noted by many
pharmacists. CONCLUSION: Prescribing had diverse meanings to pharmacists in our
study, and appeared to be context-specific. Understanding the meaning prescribing
holds for individual pharmacists is important to explore whether pharmacist's
definition of this expanded scope has shaped pharmacists' enactment of
prescribing practice.
PMID- 25121166
TI - Langerhans cell histiocytosis with atypical histiocytic marrow infiltration.
PMID- 25121167
TI - Doublet spherocytes.
PMID- 25121168
TI - Objective and subjective socioeconomic status and health symptoms in patients
following hematopoietic stem cell transplantation.
AB - OBJECTIVE: Recent research indicates that subjective socioeconomic status (SES) -
the perception of one's own SES compared with other people - is an important
predictor of cancer-related health outcomes. Subjective SES may function as a
psychosocial mechanism by which objective SES affects health, well-being, and,
more broadly, quality of life among cancer survivors. This study tested whether
the association between objective SES and indicators of quality of life was
mediated by subjective SES in a sample of cancer survivors who had undergone
hematopoietic stem cell transplantation. METHODS: Hematopoietic stem cell
transplantation survivors (N=268) completed measures of objective and subjective
SES, along with four measures related to quality of life (depressive symptoms,
health-related quality of life, symptoms of generalized distress, and
posttraumatic stress disorder symptoms). RESULTS: Higher objective SES was
associated with greater quality of life across all four measures. Subjective SES
mediated the relationship between objective SES and depressive symptoms (total
indirect effect b=-0.09, 95% confidence interval [CI] [-0.15, -0.05]),
generalized distress (total indirect effect b=-0.08, 95% CI [-0.13, -0.04]),
health-related quality of life (total indirect effect b=0.10, 95% CI [0.06,
0.17]), and posttraumatic stress disorder (total indirect effect b=-0.08, 95% CI
[-0.14, -0.04]). CONCLUSIONS: Findings extend work on subjective SES to cancer
and suggest that SES gradients in patient outcomes after cancer may reflect not
only material resources but also psychosocial factors related to rank within
social hierarchies. Further research may provide insights useful for reducing
disparities in this population
PMID- 25121170
TI - New European clinical trials regulation is published.
PMID- 25121169
TI - Faecal carriage of Pseudomonas aeruginosa in healthy humans: antimicrobial
susceptibility and global genetic lineages.
AB - The aim of this study was to analyse the Pseudomonas aeruginosa faecal carriage
rate in 98 healthy humans and to perform the phenotypic and genotypic
characterization of recovered isolates. The genetic relatedness among the
isolates was analysed by pulsed-field gel electrophoresis and multilocus sequence
typing that was compared with worldwide epidemic clones. Pseudomonas aeruginosa
was isolated from eight healthy individuals (8.2%), and two of them remained
colonized after 5 months (in one case by the same clone). All 10 isolates
(one/sample) were susceptible to 14 tested antipseudomonal agents and lacked
integron structures. Six pulsed-field gel electrophoresis patterns and six
sequence types (ST245, ST253, ST254, ST274, ST663 and the new one, ST1059) were
identified among them. Four groups of OprD alterations were detected based on
mutations and deletions related to PAO1 reference strain in our carbapenem
susceptible strains. This is the first study focused on P. aeruginosa from faecal
samples of healthy humans that provides additional insights into the
antimicrobial resistance and genetic diversity of P. aeruginosa. Although the
isolates were antimicrobial susceptible, most of the sequence types detected were
genetically related to Spanish epidemic clones or globally spread sequence types,
such as ST274 and ST253.
PMID- 25121171
TI - 2014 ASCO Annual Meeting.
PMID- 25121172
TI - 2014 SNMMI Annual Meeting.
PMID- 25121173
TI - Targeting genetic drivers of lung cancer improves survival.
PMID- 25121174
TI - Siltuximab in transplant-ineligible patients with myeloma.
PMID- 25121175
TI - Patients with polycystic kidney disease at lower risk of cancer.
PMID- 25121176
TI - Axitinib: VEGF inhibition in advanced thyroid cancer.
PMID- 25121177
TI - Cancer patients missing out on treatment for heart problems.
PMID- 25121178
TI - A new combination therapy for premenopausal breast cancer.
PMID- 25121179
TI - Ibrutinib monotherapy in chronic lymphoid leukaemia.
PMID- 25121180
TI - Enzalutamide in castration-resistant prostate cancer.
PMID- 25121181
TI - Federal court judge blocks 340B orphan drug exclusion rule.
PMID- 25121182
TI - E-cigarette market expands online.
PMID- 25121183
TI - Study estimates economic returns from UK cancer research.
PMID- 25121184
TI - Effect of partial pleurectomy on survival in mesothelioma.
PMID- 25121185
TI - Exhibition: Cancer Baby: cancer meets Kawaii culture.
PMID- 25121187
TI - Emory Guy Simmons 1920-2013.
PMID- 25121186
TI - Consensus guidelines for the management of hepatitis C infection.
AB - At prevalence of 2.7% in the early 1990's, it is estimated that approximately
500,000 people in Saudi Arabia have been exposed to the hepatitis C virus (HCV).
Over 80% of such individuals remain infected and most of them progress to chronic
hepatitis C (CHC), cirrhosis, and/or hepatocellular carcinoma (HCC). The
incidence of newly acquired hepatitis C infection in Saudi Arabia has declined
with the recent reported prevalence of approximately 1%. This decline is largely
due to the early implementation of testing of blood donors for HCV. However, it
is pertinent that measures are taken to identify patients already infected and
offer treatment to those with good prognostic factors. Hepatitis C genotype 4,
the most predominant genotype in Saudi Arabia (62%) has been resistant to
conventional interferon (IFN) therapy and sustained response rate to combination
therapy with IFN plus ribavirin (RBV) has been poor. The recently completed
Ministry of Health (MOH) clinical trial reports improved sustained virological
response (SVR) rate of 65.2% among week 12 early responders of HCV genotype 4
chronic hepatitis patients using pegylated (PEG)-IFN alfa-2a (40 KD) plus RBV.
This encouraging process calls for a change in patient management towards a more
community-based approach. With the aim of assessing these changes and defining a
management strategy for HCV infected patients in Saudi Arabia, a consensus
conference was held and consensus guidelines issued. The final recommendation
will be made available to all MOH, tertiary and non-government hospitals in the
Kingdom to provide uniform care to all CHC patients. Based on the SVR of the
above mentioned clinical trial, the committee recommends treatment for patients
with histologically proven CHC, with elevated serum alanine aminotransferase
(ALT) and positive HCV ribonucleic acid (RNA). Patients with normal serum ALT may
not be treated if liver histology is normal or reveals only minimal changes.
Patients with decompensated cirrhosis should not be treated. Hepatitis C virus
genotype 4 patients should be treated with combination therapy of PEG IFN alfa-2a
(180 MUg/week) plus RBV (1000 - 1200 mg daily according to body weight) for 48
weeks. Patients with HCV non-genotype 4 may also be treated with combination
therapy of PEG-IFN plus RBV, but genotypes 2 and 3 patients can be treated for 6
months only. Stringent monitoring for virological biochemical responses is
eminent and provides the opportunity to interrupt treatment at week 12 in non
responders. A strong counseling program should be available for untreated
patients, relapsers and non-responders. An exit program for liver transplantation
should also be set up. It is likely that some of the consensus recommendations
will have to be revised in the short-term, as the results of ongoing studies
become available. Future research in advances in diagnosis, pathogenesis, natural
history, management and prevention should be encouraged and newer therapies for
CHC patients should be sought for non-responders.
PMID- 25121189
TI - A 49 year-old woman with a pineal mass.
PMID- 25121188
TI - Climate-change impacts on sandy-beach biota: crossing a line in the sand.
AB - Sandy ocean beaches are iconic assets that provide irreplaceable ecosystem
services to society. Despite their great socioeconomic importance, beaches as
ecosystems are severely under-represented in the literature on climate-change
ecology. Here, we redress this imbalance by examining whether beach biota have
been observed to respond to recent climate change in ways that are consistent
with expectations under climate change. We base our assessments on evidence
coming from case studies on beach invertebrates in South America and on sea
turtles globally. Surprisingly, we find that observational evidence for climate
change responses in beach biota is more convincing for invertebrates than for
highly charismatic turtles. This asymmetry is paradoxical given the better
theoretical understanding of the mechanisms by which turtles are likely to
respond to changes in climate. Regardless of this disparity, knowledge of the
unique attributes of beach systems can complement our detection of climate-change
impacts on sandy-shore invertebrates to add rigor to studies of climate-change
ecology for sandy beaches. To this end, we combine theory from beach ecology and
climate-change ecology to put forward a suite of predictive hypotheses regarding
climate impacts on beaches and to suggest ways that these can be tested.
Addressing these hypotheses could significantly advance both beach and climate
change ecology, thereby progressing understanding of how future climate change
will impact coastal ecosystems more generally.
PMID- 25121190
TI - 74 year-old woman with systemic lupus erythematosis and recent onset ataxia.
PMID- 25121191
TI - 72 year old female with leg weakness.
PMID- 25121192
TI - A 54 year-old man with progressive vision and hearing loss.
PMID- 25121340
TI - Resonance electron attachment to tetracyanoquinodimethane.
AB - Resonance interaction of low energy (0-14 eV) electrons with gas-phase 7,7,8,8
tetracyanoquinodimethane (TCNQ) was investigated using dissociative electron
attachment (DEA) spectroscopy. Spectral features associated with formation of
long-lived TCNQ molecular negative ions are detected at incident electron
energies of 0.3, 1.3, and 3.0 eV. A variety of negative fragments is observed
around 4 eV, and slow (microseconds) dissociative decay channels are detected at
about 3 eV, in competition with simple re-emission of the captured electron. The
average electron detachment time from the TCNQ(-) negative ions formed at 3 eV
was evaluated to be 250 MUs. The experimental findings are interpreted with the
support of density functional theory (DFT) calculations of the empty orbital
energies, scaled with an empirical equation, and by comparison with earlier
electron transmission spectroscopy (ETS) data. A possible mechanism for the
unusual formation of long-lived molecular anions above zero energy (up to 3 eV)
is briefly discussed. The present results on the interactions between electrons
and isolated TCNQ molecules could give more insight into processes observed in
TCNQ adsorbates under conditions of excess negative charge. In particular,
electron-stimulated surface reactions are hypothesized, likely occurring when
condensed TCNQ molecules are exposed to electron beam irradiation.
PMID- 25121341
TI - Optimization of liganded polyethylenimine polyethylene glycol vector for nucleic
acid delivery.
AB - The delivery of nucleic acids into cells is an attractive approach for cancer
therapy. Polyethylenimine (PEI) is among the most efficient nonviral carriers.
Recent studies have demonstrated that PEI can be conjugated to targeting ligands,
such as epidermal growth factor (EGF) and transferrin (Schaffert et al., 2011;
Abourbeh et al., 2012; Ogris et al., 1999). Herein we present a simplified
protocol for producing homogeneous preparations of PEGylated linear PEI: LPEI
PEG2k. We generated two well-characterized copolymers, with ratios of LPEI to PEG
of 1:1 and 1:3. These copolymers were further conjugated through disulfide bonds
to a Her-2 targeting moiety, Her-2 affibody. This reaction yielded two
triconjugates that target Her-2 overexpressing tumors. Polyplexes were formed by
complexing plasmid DNA with the triconjugates. We characterized the biophysical
properties of the conjugates, and found that the triconjugate 1:3 polyplex had
lower zeta potential, larger particle size, and more heterogeneous shape than the
triconjugate 1:1 polyplex. Triconjugate 1:1 and triconjugate 1:3 polyplexes were
highly selective toward cells that overexpress Her-2 receptors, but triconjugate
1:1 polyplex was more efficient at gene delivery. Our studies show that the
biophysical and biological properties of the conjugates can be profoundly
affected by the ratio of LPEI:PEG2k:ligand. The procedure described here can be
adapted to generate a variety of triconjugates, simply by changing the targeting
moiety.
PMID- 25121342
TI - Maternal lipids in pre-eclampsia: innocent bystander or culprit?
AB - Pre-eclampsia continues to be a challenge--to understand the underlying
pathogenesis and to prevent or treat in the clinical setting. One area of
potential therapies opening up is treatment of maternal lipids and clinical
trials are underway using statins in early pre-eclampsia. At present, most
potential therapies to treat lipids cannot be recommended for general use in
pregnancy and if we were to target maternal lipids to reduce rates of pre
eclampsia, very large numbers of women may need to be treated. Prior to reaching
that point, we first need to understand whether maternal lipids are pathogenic in
the processes underlying pre-eclampsia. The aim of this review is to examine the
role of lipids in the pathogenesis and outcomes of pre-eclampsia, how abnormal
lipid genes may be implicated and consider whether treatment of hyperlipidemia
has a more general place in the prevention or treatment of pre-eclampsia.
PMID- 25121343
TI - Synthetic methods for compounds having CF3-S units on carbon by
trifluoromethylation, trifluoromethylthiolation, triflylation, and related
reactions.
PMID- 25121344
TI - Proteins immobilization on the surface of modified plant viral particles coated
with hydrophobic polycations.
AB - Two hydrophobic cations based on poly-N-ethyl-vinylpyridine were used to produce
biologically active complexes. The complexes obtained from tobacco mosaic virus
(TMV) spherical particles (SPs), hydrophobic polycation, and a model protein were
stable and did not aggregate in solution, particularly at high ionic strengths.
The nucleic acid-free SPs were generated by thermal remodeling of the TMV
(helical rod-shaped plant virus). The model protein preserved its antigenic
activity in the ternary complex (SP-polycation-protein). Immobilization of
proteins on the surface of SPs coated with hydrophobic cation is a promising
approach to designing biologically active complexes used in bionanotechnologies.
PMID- 25121346
TI - NMR, calorimetry, and computational studies of aqueous solutions of N-methyl-2
pyrrolidone.
AB - N-Methyl-2-pyrrolidone (NMP) is a solvent with applications in different
industrial fields. Although largely employed in aqueous mixtures, little is known
on the structural and dynamic properties of this system. In order to improve the
knowledge on NMP aqueous solutions, useful to the development of their
applications, NMR spectroscopy, calorimetric titration, and puckering analysis of
molecular dynamics (MD) simulations were employed in this work. Our calorimetric
study evidenced the presence of strong interactions between NMP and water and
revealed that, under comparable conditions, the solvation of NMP by water results
in an interaction stronger than the solvation of water by NMP. Overall, the
changes of (1)H and (13)C chemical shifts and 2D ROESY spectra upon dilution
suggested a preferential location of water nearby the carbonyl group of NMP and
the formation of hydrogen bonding between these two molecules. In parallel,
observation of correlation times by (13)C NMR spectroscopy evidenced a different
dynamic behavior moving from the NMP-rich region to the water-rich region,
characterized by a maximum value at about 0.7 water mole fraction. MD simulations
showed that the NMP conformation remains the same over the whole concentration
range. Our results were discussed in terms of changes in the NMP assembling upon
dilution.
PMID- 25121345
TI - Clinical Manifestations and Outcomes of Syphilis-associated Uveitis in Northern
Spain.
AB - PURPOSE: To describe the clinical characteristics and to assess visual prognosis
of patients with syphilis-associated uveitis in northern Spain. METHODS:
Retrospective review of clinical records in eight general uveitis referral
centers. RESULTS: Since the year 2000, 50 patients have been diagnosed: 31 men
and 19 women; median age was 41 (19-76) years. A total of 34% were co-infected
with HIV and 24% presented systemic manifestations of syphilis. Median initial
visual acuity and vision at last visit in 93 affected eyes was 20/50 (20/20
20/2000) and 20/22 (20/20-20/2000), respectively (p < .0001). The most frequent
manifestation was papillitis (33.3%). Fifty percent of eyes with macular edema on
admission presented worsening of visual acuity at last visit, whereas frequency
of worsening in eyes without edema was 7.1% (p = 0.009). CONCLUSIONS: In our
series, patients with syphilitic uveitis were more usually middle-aged men and
were frequently co-infected with HIV. Although most patients showed posterior
segment involvement, visual prognosis was good.
PMID- 25121348
TI - An oxysulfate Fe2O(SO4)2 electrode for sustainable Li-based batteries.
AB - High-performing Fe-based electrodes for Li-based batteries are eagerly pursued
because of the abundance and environmental benignity of iron, with especially
great interest in polyanionic compounds because of their flexibility in tuning
the Fe(3+)/Fe(2+) redox potential. We report herein the synthesis and structure
of a new Fe-based oxysulfate phase, Fe2O(SO4)2, made at low temperature from
abundant elements, which electrochemically reacts with nearly 1.6 Li atoms at an
average voltage of 3.0 V versus Li(+)/Li, leading to a sustained reversible
capacity of ~125 mAh/g. The Li insertion-deinsertion process, the first ever
reported in any oxysulfate, entails complex phase transformations associated with
the position of iron within the FeO6 octahedra. This finding opens a new path
worth exploring in the quest for new positive electrode materials.
PMID- 25121347
TI - Synthesis, characterization, and biological evaluation of new Ru(II) polypyridyl
photosensitizers for photodynamic therapy.
AB - Two Ru(II) polypyridyl complexes, Ru(DIP)2(bdt) (1) and [Ru(dqpCO2Me)(ptpy)](2+)
(2) (DIP = 4,7-diphenyl-1,10-phenanthroline, bdt = 1,2-benzenedithiolate,
dqpCO2Me = 4-methylcarboxy-2,6-di(quinolin-8-yl)pyridine), ptpy = 4'-phenyl
2,2':6',2"-terpyridine) have been investigated as photosensitizers (PSs) for
photodynamic therapy (PDT). In our experimental settings, the phototoxicity and
phototoxic index (PI) of 2 (IC50(light): 25.3 MUM, 420 nm, 6.95 J/cm(2); PI >4)
and particularly of 1 (IC50(light): 0.62 MUM, 420 nm, 6.95 J/cm(2); PI: 80) are
considerably superior compared to the two clinically approved PSs porfimer sodium
and 5-aminolevulinic acid. Cellular uptake and distribution of these complexes
was investigated by confocal microscopy (1) and by inductively coupled plasma
mass spectrometry (1 and 2). Their phototoxicity was also determined against the
Gram-(+) Staphylococcus aureus and Gram-(-) Escherichia coli for potential
antimicrobial PDT (aPDT) applications. Both complexes showed significant aPDT
activity (420 nm, 8 J/cm(2)) against Gram-(+) (S. aureus; >6 log10 CFU reduction)
and, for 2, also against Gram-(-) E. coli (>4 log10 CFU reduction).
PMID- 25121349
TI - Comparing apples to oranges: comparative case study of 2 produce carts in
Chicago.
PMID- 25121350
TI - Information-seeking among chronic disease prevention staff in state health
departments: use of academic journals.
AB - Use of scientific evidence aids in ensuring that public health interventions have
the best possible health and economic return on investment. We describe use of
academic journals by state health department chronic disease prevention staff to
find public health evidence. We surveyed more than 900 state health department
staff from all states and the District of Columbia. Participants identified top
journals or barriers to journal use. We used descriptive statistics to examine
individual and aggregate state health department responses. On average, 45.7% of
staff per state health department use journals. Common barriers to use included
lack of time, lack of access, and expense. Strategies for increasing journal use
are provided.
PMID- 25121351
TI - Hypertension among US adults by disability status and type, National Health and
Nutrition Examination Survey, 2001-2010.
AB - The prevalence of hypertension among people with disabilities is not well
understood. We combined data from the 2001-2010 National Health and Nutrition
Examination Survey to obtain estimates of hypertension prevalence by disability
status and type (cognitive, hearing, vision, or mobility limitation) and assess
the association between disability and hypertension. Overall, 34% of adults with
disabilities had hypertension compared with 27% of adults without disabilities;
adults with mobility limitations were more likely to have hypertension than
adults without disabilities (adjusted prevalence ratio: 1.23; 95% confidence
interval: 1.16-1.32). Our results suggest that adults living with disabilities
are an important subpopulation to include in hypertension reporting and
intervention efforts.
PMID- 25121352
TI - Factors related to coronary heart disease risk among men: validation of the
Framingham Risk Score.
AB - INTRODUCTION: Coronary heart disease (CHD) remains a leading cause of death in
the United States. The Framingham Risk Score (FRS) was developed to help
clinicians in determining their patients' CHD risk. We hypothesize that the FRS
will be significantly predictive of CHD events among men in the Aerobics Center
Longitudinal Study (ACLS) population. METHODS: Our study consisted of 34,557 men
who attended the Cooper Clinic in Dallas, Texas, for a baseline clinical
examination from 1972 through 2002. CHD events included self-reported myocardial
infarction or revascularization or death due to CHD. During the 12-year follow-up
587 CHD events occurred. Multivariable-adjusted hazard ratios generated from ACLS
analysis were compared with the application of FRS to the Framingham Heart Study
(FHS). RESULTS: The ACLS cohort produced similar hazard ratios to the FHS. The
adjusted Cox proportional hazard model revealed that men with total cholesterol
of 280 mg/dL or greater were 2.21 (95% confidence interval (CI), 1.59-3.09) times
more likely to have a CHD event than men with total cholesterol from 160 through
199mg/dL; men with diabetes were 1.63 (95% CI, 1.35-1.98) times more likely to
experience a CHD event than men without diabetes. CONCLUSION: The FRS
significantly predicts CHD events in the ACLS cohort. To the best of our
knowledge, this is the first report of a large, single-center cohort study to
validate the FRS by using extensive laboratory and clinical measurements.
PMID- 25121353
TI - A new tumour suppression mechanism by p27Kip1: EGFR down-regulation mediated by
JNK/c-Jun pathway inhibition.
AB - p27Kip1 is a potent inhibitor of cyclin-dependent kinases that drive G1-to-S cell
cycle transition. Reduced p27Kip1 expression is prevalent in a wide range of
human tumours; however, the exact mechanism(s) of p27Kip1-mediated tumour
suppression remains obscure. In the present study, we identified a close inverse
relationship between p27Kip1 and EGFR (epidermal growth factor receptor)
expression: the parental T24 human bladder cancer cells had high p27Kip1
expression but low EGFR expression and, in striking contrast, the metastatic
derivative of T24 (T24T) had low p27Kip1 expression but high EGFR expression.
This relationship was also found in various human cancer tissues, and was not
only just correlative but also causal; depletion of p27Kip1 in MEF (mouse
embryonic fibroblast) cells resulted in markedly elevated EGFR expression, a
result reproducible with an Egfr promoter-luciferase reporter in both T24 and MEF
cells, suggesting transcriptional repression of EGFR by p27Kip1. Indeed, p27Kip1
was found to regulate EGFR expression via the JNK (c-Jun N-terminal kinase)/c-Jun
transcription factor: p27Kip1 deficiency activated JNK/c-Jun, whereas inhibition
of JNK/c-Jun by dominant-negative mutants dramatically repressed Egfr
transcription. Furthermore, the proximal promoter of the Egfr gene was crucial
for its transcription, where the recruiting activity of c-Jun was much greater in
p27Kip1-/- cells than in p27Kip1+/+ cells. Introduction of GFP-p27Kip1 into T24T
cells suppressed JNK/c-Jun activation, EGFR expression and anchorage-independent
growth. The results of the present study demonstrate that p27Kip1 suppresses
JNK/c-Jun activation and EGFR expression in MEFs and human bladder cancer cells,
and the results obtained are consistent with those from human cancer specimens.
The present study provides new insights into p27Kip1 suppression of cancer cell
growth, migration and metastasis.
PMID- 25121354
TI - Initial staging of Hodgkin's disease: role of contrast-enhanced 18F FDG PET/CT.
AB - The objective of this study was to compare the diagnostic accuracy of positron
emission tomography/low-dose computed tomography (PET/ldCT) versus the same
technique implemented by contrast-enhanced computed tomography (ceCT) in staging
Hodgkin's disease (HD).Forty patients (18 men and 22 women, mean age 30 +/- 9.6)
with biopsy-proven HD underwent a PET/ldCT study for initial staging including an
unenhanced low-dose computed tomography for attenuation correction with positron
emission tomography acquisition and a ceCT, performed at the end of the PET/ldCT
scan, in the same exam session. A detailed datasheet was generated for illness
locations for separate imaging modality comparison and then merged in order to
compare the separate imaging method results (PET/ldCT and ceCT) versus merged
results positron emission tomography/contrast-enhanced computed tomography
(PET/ceCT). The nodal and extranodal lesions detected by each technique were then
compared with follow-up data that served as the reference standard.No significant
differences were found at staging between PET/ldCT and PET/ceCT in our series.
One hundred and eighty four stations of nodal involvement have been found with no
differences in both modalities. Extranodal involvement was identified in 26 sites
by PET/ldCT and in 28 by PET/ceCT. We did not find significant differences
concerning the stage (Ann Arbor).Our study shows a good concordance and
conjunction between PET/ldCT and ceCT in both nodal and extranodal sites in the
initial staging of HD, suggesting that PET/ldCT could suffice in most of these
patients.
PMID- 25121356
TI - Increased risk of end-stage renal disease in patients with renal cell carcinoma:
a 12-year nationwide follow-up study.
AB - The effect of renal cell carcinoma (RCC) on the risk for end-stage renal disease
(ESRD) has not been confirmed. The present population-based study used the claims
data from the Taiwan National Health Institutes from 1998 to 2010 to compare the
risk for ESRD in patients with and without RCC.The study cohort consisted of 2940
patients who had newly diagnosed with RCC but no history of ESRD; the control
cohort consisted of 23,520 matched patients without RCC. Cox proportional hazard
regressions were performed to compute ESRD risk after adjusting for possible
confounding factors. Kaplan-Meier analysis and the log-rank test were also used
to compare patients and controls.A total of 119 patients in the RCC group
(incidence rate: 119/2940; 4.05%) and 160 patients in the control group
(incidence rate: 160/23,520; 0.68%) were diagnosed with ESRD during the follow-up
period. After adjusting for potential confounders, the RCC group had an ESRD
hazard ratio (HR) of 5.63 [95% confidence interval (CI): 4.37-7.24] relative to
the control group. In addition, among patients with RCC, females (adjusted HR:
6.95, 95% CI: 4.82-10.1) had a higher risk for ESRD than males (adjusted HR:
4.79, 95% CI: 3.37-6.82). Finally, there were significant joint effects of
chronic kidney disease and diabetes on increasing the risk of ESRD in patients
with and without RCC (P < 0.01). The limitations of this study include the
retrospective design and the inability to assess methods of treatment and measure
the aggressiveness of RCC.Our data indicates that RCC is an independent risk
factor for ESRD, especially in females.
PMID- 25121359
TI - Selective response inversion to NO2 and acetic acid in ZnO and CdS nanocomposite
gas sensor.
AB - High sensitivity zinc oxide (ZnO) tetrapods (TPs) have been functionalized by
nucleating cadmium sulphide (CdS) nanoparticles (NPs) directly on their surface
with a spotted coverage thanks to an optimized synthesis in dimethylformamide
(DMF). The obtained hybrid coupled material has been used to realize a gas
sensing device with a highly porous nanostructured network, in which the proper
alternation of ZnO-TPs and CdS-NPs gives rise to unconventional chemoresistive
behaviours. Among the different tested gases and vapours, the sensor showed a
unique fingerprint response-inversion between 300 degrees C and 400 degrees C
only for nitrogen dioxide (NO2) and acetic acid (CH3COOH).
PMID- 25121357
TI - High delta-like ligand 4 (DLL4) is correlated with peritumoral brain edema and
predicts poor prognosis in primary glioblastoma.
AB - Delta-like ligand 4 (DLL4), 1 of the 5 known Notch ligands, is involved in a
variety of tumor initiation and progression, particularly in the process of tumor
angiogenesis. However, the clinical and prognostic significance of DLL4 in
glioblastoma have not been fully elucidated.Tumor tissues from 69 glioblastoma
patients were analyzed using immunohistochemistry for DLL4 expression.
Peritumoral brain edema (PTBE) on preoperative magnetic resonance imaging of
these patients and the relationship with DLL4 expression were evaluated. The
effect on prognosis was assessed by using the Kaplan-Meier survival and the Cox
proportional hazard model.The results showed that elevated DLL4 expression was
primarily distributed in the cytoplasm of tumor vascular endothelial cells and
rarely detected in tumor cells. Univariate analysis indicated significant
correlation of high DLL4 expression with shorter time to progression (TTP) (P <
0.001) and overall survival (OS) (P < 0.001) in glioblastoma. Multivariate
analysis confirmed high DLL4 expression as an unfavorable prognostic indicator
for TTP (P < 0.001) and OS (P < 0.001), independent of age, gender, symptom
duration, resection degree, and PTBE. Importantly, the study also found that DLL4
expression was positively related with PTBE (Spearman's test: r = 0.845, P <
0.001). A multiple linear regression model was constructed to confirm that the
positive index of DLL4 was associated with an increase in maximum extent of PTBE
(P < 0.001).It is thus concluded that DLL4 is correlated with PTBE and may be
useful for predicting prognosis in glioblastoma.
PMID- 25121358
TI - Membranous nephropathy with crescents in a patient with Hashimoto's thyroiditis:
a case report.
AB - Membranous nephropathy is a common cause of nephrotic syndrome in adults. It
usually occurs secondary to underlying disease processes such as autoimmune
disorders, malignancy, infection, and drugs. The presentation of nephrotic
syndrome with concomitant precipitous decline in renal function warrants
investigation of a coexistent disorder.We report the case of a 30-year-old male
who presented with symptoms and signs of hypothyroidism.A diagnosis of
Hashimoto's thyroiditis was contemplated based on the presence of high serum
levels of antithyroglobulin and antithyroid peroxidase antibodies. Upon
initiation of treatment with levothyroxine, patient symptomatology improved;
however, the laboratory studies demonstrated continued elevated creatinine,
hematuria, and proteinuria, which had not been addressed. Two months following
treatment initiation, he had progressive deterioration in renal function and
proteinuria. A renal biopsy revealed coexistent necrotizing and crescentic
glomerulonephritis and membranous nephropathy.The final diagnosis was
necrotizing, crescentic glomerulonephritis with superimposed membranous
nephropathy likely secondary to Hashimoto's thyrodiitis.Induction treatment with
oral cyclophosphamide and prednisone was started.At the end of 6 months of
treatment, there was improvement in renal function and proteinuria and
maintenance treatment with azathioprine and low-dose prednisone was initiated.
This case highlights the importance of precise and detailed evaluation of
patients with autoimmune diseases such as Hashimoto's thyroiditis particularly in
the presence of active urine sediment. Proper evaluation and diagnosis of such
patients has implications on the prognosis and response to treatment.
PMID- 25121355
TI - Characteristics of fecal and mucosa-associated microbiota in Chinese patients
with inflammatory bowel disease.
AB - The intestinal microbiota plays an important role in the pathogenesis of
inflammatory bowel disease (IBD), and geographical and genetic backgrounds impact
the composition of the intestinal microbiota. However, there is a lack of
evidence regarding the overall changes and characteristics of fecal-associated
microbiota (FAM) and mucosa-associated microbiota (MAM) in Chinese patients with
IBD. We recruited 26 patients with Crohn's disease (CD), 46 patients with
ulcerative colitis (UC), and 21 healthy individuals; we collected matched fresh
fecal and mucosal samples from the same subjects. The microbial communities were
studied by 454-pyrosequencing. Community-wide changes in FAM and MAM were
observed in patients with IBD. The proportion of several butyrate-producing
bacteria, such as of the genera Roseburia, Coprococcus, and Ruminococcus were
significantly reduced, whereas the pathogens Escherichia-Shigella and
Enterococcus were prevalent in patients with IBD. FAM and MAM were similar
between CD and UC. FAM differed from MAM in healthy individuals and patients with
UC. In conclusion, the compositions of FAM and MAM were altered in patients with
IBD. The reduction of butyrate-producing bacteria and the increase in
opportunistic pathogens might be associated with the pathogenesis of IBD.
PMID- 25121360
TI - Anaphylactic cardiac collapse, sudden death and the Kounis syndrome.
PMID- 25121361
TI - A pilot study on expression of toll like receptors (TLRs) in response to herpes
simplex virus (HSV) infection in acute retinal pigment epithelial cells (ARPE)
cells.
AB - INTRODUCTION: Toll like receptors (TLRs) have been proven to play an important
role in mounting the innate immune response in an infected host. The expression
of TLRs against herpes simplex virus (HSV) have not been studied in retinitis.
Therefore, the current study was undertaken to determine the same using the
retinal pigment epithelial (ARPE-19) cell line. MATERIALS AND METHODS: APRE cells
cultured in vitro were challenged with HSV 1 and 2 standard strains and 20 other
clinical isolates. The cells were observed for cytopathic changes. The cell
culture harvest was subjected to RNA extraction using a Total RNA mini kit. The
RNA was subjected to reverse transcriptase polymerase chain reaction (PCR) for
the amplification of TLRs 3, 4 and 9 and GAPDH housekeeping gene. The amplified
products were subjected to electrophoresis on a 2% agarose gel and viewed under a
transilluminator. RESULTS: TLR 3 and 4 were expressed by ARPE treated with all
the 22 isolates. TLR 9 expression was seen in 16 of the 22 isolates. Bacterial
contamination was ruled out by subjecting the harvests to PCR amplification of
16sRNA gene amplification of the eubacterial genome. CONCLUSIONS: The expression
of TLR 4 has been reported for the first time in HSV infection. TLR 4 along with
TLR 3 and 9 is responsible for the antiviral response in HSV infections.
PMID- 25121362
TI - Outcome of surgically treated octogenarians with breast cancer.
AB - CONTEXT: Breast cancer is the commonest cancer in women worldwide and its
incidence increases with increasing age. In an era of evidence-based practice,
there is a paucity of evidence relating to the management of breast cancer in an
oncogeriatric population. The authors define oncogeriatrics as cancer in patients
aged 80 years or more. AIM: The study aimed to evaluate the survival benefit of
surgically managed octogenarians with breast cancer. MATERIALS AND METHODS: This
was a retrospective study of octogenarians diagnosed with breast cancer over a 5
year period and who were treated surgically. Kaplan-Meier survival analysis was
used to determine the overall survival. The differences in survival were tested
using the logrank (Mantel-Cox) test. A P-value of <0.05 was considered to be
statistically significant. RESULTS: One hundred patients were included (median
age- 84 years, median follow up 3.3 years). A validated adult comorbidity
evaluation-27 (ACE-27) index score system was used to characterize patient
comorbidities. Fourteen percent of patients had severe comorbidities, 55%
nonsevere, 11% no comorbidities, and 20% with unknown comorbidities. The estrogen
receptor was positive in 67% of tumors. Eighty-four percent had mastectomy and
15% had wide local excision. Sixty-eight percent had axillary lymph node
dissection, 10% had sentinel lymph node biopsy, and 5% had no axillary surgery.
The majority (72%) of the tumors were pathologically T1 or T2 tumor. The
Nottingham Prognostic Index (NPI) mean score was 4.4. The Kaplan-Meier survival
analysis showed a median survival of 5 years. Forty-eight percent died during the
observation period, with 54.2% of this group dying of causes unrelated to breast
cancer. CONCLUSION: The surgically treated octogenarians in our sample had an
acceptable survival outcome.
PMID- 25121363
TI - Outcomes of surgical site infections in orthopedic trauma surgeries in a tertiary
care centre in India.
AB - BACKGROUND: Surgical site infections (SSIs) still cause significant morbidity and
mortality despite advances in trauma care. We have studied in this paper the rate
of SSIs, their outcomes in patients undergoing interventions for trauma and SSI
trends in developing countries. MATERIALS AND METHODS: A 16-month study (May,
2011- August, 2012) was carried out. Patients undergoing interventions for
orthopedic trauma were followed and assessed for SSIs and their outcomes and
antimicrobial sensitivity patterns of the micro-organisms isolated were noted and
correlated. RESULTS: A total of 40 (4.4%) confirmed cases of SSIs were identified
among 852 patients of orthopedic trauma. Based on the new CDC criteria, after
ruling out cellulitis, only 24 (2.6%) were found to have SSIs. A total of 12.5%
of the SSIs were detected during follow-up. Acinetobacter baumannii was the
predominant organism as also Staphylococcus aureus. Outcomes observed included
changes in antibiotic regime, revision surgery, readmission to hospital and
deaths. CONCLUSION: SSI is prevalent in orthopaedic trauma patients and an active
surveillance program will help in early management and prevention.
PMID- 25121364
TI - Lower levels of serum high-density lipoprotein cholesterol are associated with a
worse Duke treadmill score in men but not in women.
AB - BACKGROUND: High-density lipoprotein cholesterol (HDL-C) levels are inversely
related to the atherosclerotic burden and are higher in women than in men. We
aimed to investigate the sex-specific relationship between serum HDL-C levels and
the Duke treadmill score (DTS) in this study. MATERIALS AND METHODS: A total of
111 patients (59 men, 42 women) with suspected coronary artery disease (CAD) who
underwent exercise treadmill test (EST) were included. Fasting blood samples were
obtained for the assessment of serum lipid levels. DTS was calculated for each
patient based on EST findings including ST segment deviation and symptoms.
RESULTS: Patients were categorized into a moderate to high risk group based on
the DTS score (group-I: 38 patients) and a low risk group (group-II: 63
patients). There was a significant positive correlation between serum HDL-C
levels and DTS (r = 0.230; P=0.021). The mean HDL-C level was significantly
higher in group-II relative to group-I (49.25 +/-11.21 vs. 44.43 +/- 11.18,
respectively, P = 0.04). An HDL-C level less than the cut-off value of 41.39
mg/dL predicted a moderate to severe risk DTS with 65% sensitivity and 69%
specificity in men (area under curve = 0.732, P = 0.004), but not in women (area
under curve = 0.505, P = 0.958). After adjustment for traditional CAD risk
factors (age, sex, and smoking status), the relationship of DTS to HDL-C remained
significant. (P = 0.030; adjusted OR = 0.948 [95% CI, 0.904-0.995]). CONCLUSION:
Low HDL-C levels may be associated with a moderate to high risk Duke treadmill
score in men, but not in women. Further research is required to clarify the sex
specific relationship between HDL-C and DTS.
PMID- 25121365
TI - Association of polymorphisms of CYP2C9, CYP2C19, and ABCB1, and activity of P
glycoprotein with response to anti-epileptic drugs.
AB - BACKGROUND AND OBJECTIVE: Epilepsy, the most common neurological disorder, has
treatment failure rate of 20 to 25%. Inter-individual variability in drug
response can be attributed to genetic polymorphism in genes encoding different
drug metabolizing enzymes, drug transporters (P-gp), and enzymes involved in
sodium channel biosynthesis. The present study attempted to evaluate association
of polymorphisms of CYP2C9, CYP2C19, and ABCB1, and P-gp activity with treatment
response in patients with epilepsy. MATERIALS AND METHODS: Patients with epilepsy
on phenytoin and/or phenobarbital and/or carbamazepine were categorized into
responders and non-responders as per the International League Against Epilepsy.
Plasma drug concentration was estimated by high-performance liquid
chromatography. P-gp activity was measured by flow cytometry using rhodamine
efflux. The polymerase chain reaction (PCR-RFLP) was used to study polymorphisms
of ABCB1 (C3435T), CYP2C9 (416 C > T, and 1061 A > T), and CYP2C19 (681 G > A and
636 G > A). RESULTS: Of total 117 patients enrolled in this study, genotype data
was available for 115 patients. P-gp activity was higher in non-responders (n =
68) compared to responders (n = 47) (P<0.001). No association of 416 C > T and
1061 A > T in CYP2C9 or 681 G > A and 636 G > A in CYP2C19 was observed with
response phenotype in genotypic analysis. Significant genotypic (odds ratio, OR =
4.5; 95% CI, 1.04 to 20.99) and allelic association (OR = 1.73; 95% CI, 1.02 to
2.95) was observed with ABCB1 C3435T and response phenotype. CONCLUSIONS: The
response to antiepileptics seems to be modulated by C3435T in ABCB1 or P-gp
activity. At present, role of other genetic factors in treatment responsiveness
in epilepsy appears limited, warranting analysis in a larger cohort.
PMID- 25121367
TI - Influence of alcohol on condom use pattern during non-spousal sexual encounter in
male migrant workers in north India.
AB - CONTEXT: Migrant workers constitute an important risk group for Human
Immunodeficiency Virus/Acquired Immuno-Deficiency Syndrome transmission in India.
Alcohol consumption before sexual intercourse has been postulated to influence
condom use practices. This study aimed to assess this association with regard to
non-spousal sexual encounters among male migrant workers in northern India.
MATERIALS AND METHODS: A cross-sectional facility-based survey was conducted in
2011. Male migrant workers aged >=18 years, who were born outside Haryana, who
had moved to the current location after 15 years of age,had worked in the current
factory for at least 1 year, who were willing to participate and were able to
give written, informed consent were included in the study. A consecutive sampling
was performed. Descriptive, bivariate and multiple logistic regression analyses
were carried out. RESULTS: A total of 162 participants reported having
experienced non-spousal sexual encounters in the last 1 year. The proportion of
men who reported not having used a condom at their last non-spousal sexual
encounter was 59.3%, and 78.4% of the men reported having consumed alcohol in the
last 1 year. About 48.1% of men reported having consumed alcohol before their
last non-spousal sexual encounter. Men who consumed alcohol were three times more
likely to not use a condom at their last non-spousal sexual encounter (OR = 3.1,
95% CI: 1.5-6.4). This association persisted even after adjusting for relevant
confounders. CONCLUSION: Alcohol consumption had a negative influence on condom
use during non-spousal sexual encounter among male migrant workers. An integrated
approach to promote condom use and reduce alcohol consumption among migrant men
needs to be undertaken through targeted intervention strategies.
PMID- 25121366
TI - A prospective study of prevalence and association of peripheral neuropathy in
Indian patients with newly diagnosed type 2 diabetes mellitus.
AB - BACKGROUND: Diabetic peripheral neuropathy (DPN) predisposes to foot ulceration
and gangrene. It has been reported that DPN is lower in Indians relative to
Caucasians. Studies among recent onset patients with type 2 diabetes mellitus
(T2DM) are very few. We studied the prevalence and risk factors of DPN in
patients with newly diagnosed T2DM. MATERIALS AND METHODS: We prospectively
studied 195 consecutive patients over age 30 with a duration of diabetes <=6
months. All underwent a clinical and biochemical evaluation and were screened for
DPN using Neuropathy Symptom Score (NSS) and Neuropathy Disability Score (NDS) as
well as the vibration perception threshold using a biothesiometer. We compared
the prevalence of peripheral neuropathy (PN) in 75 age- and sex-matched healthy
controls. RESULTS: The cases had a mean age of 47.6 +/- 10.2 years (59% males)
and duration of symptoms of 5.9 +/- 8.2 months prior to presentation. The overall
prevalence of DPN was 29.2% [95% CI 22.8-35.7]. PN among matched control was
10.7% (95% CI 3.5-17.8). The prevalence of DPN showed an increasing trend with
age (trend chi-square 11.8, P = 0.001). Abnormal vibration perception threshold
was present in 43.3% (95% CI 36.3-50.3) of cases and had a significant
correlation with NDS (P = 0.000). Abnormal monofilament testing was present in
6.1% of cases (95% CI 2.7- 9.5). A logistic regression analysis showed that DPN
was independently associated with age (P = 0.002) and duration of diabetes prior
to presentation (P = 0.02) but not with body mass index, plasma glucose, or
HbA1c. CONCLUSIONS: Our study showed high prevalence of PN in recently diagnosed
patients with T2DM, which was independently associated with age and duration of
symptoms of diabetes prior to the diagnosis. Screening for DPN at diagnosis of
diabetes is warranted, especially among older subjects.
PMID- 25121369
TI - Brachial plexus injury in live related donor hepatectomy: a chart review.
AB - Retrieval of the partial liver graft is a complicated and time-consuming
procedure and reported to be associated with brachial plexus injury. We present a
case series of brachial plexus injury in live related donor hepatectomy of 95
donors analyzed retrospectively. Seven donors suffered from brachial plexus
injuries of varying severity and duration. Out of these, one donor had residual
paresis. The reasons could be application of retractors, which may have led to
traction and compression above the nerve roots.
PMID- 25121368
TI - Prevalence of gastro-esophageal reflux disease in patients with difficult to
control asthma and effect of proton pump inhibitor therapy on asthma symptoms,
reflux symptoms, pulmonary function and requirement for asthma medications.
AB - BACKGROUND: The hypothesis that GER can trigger or exacerbate asthma is supported
by several clinical trials that have shown amelioration in asthma symptoms and/or
an improvement in pulmonary function after antireflux therapy. AIMS: To
investigate the prevalence of GER in patients with difficult to control asthma
and to determine the effect of omeprazole on asthma symptoms, reflux symptoms,
pulmonary function and on the requirement of asthma medications. MATERIALS AND
METHODS: Patients with difficult to control asthma were recruited into the study.
All patients underwent esophageal manometry and 24 hour esophageal pH monitoring.
Pulmonary function tests were done before and after treatment. The severity of
asthma and reflux was assessed by a 1 week pulmonary symptom score(PSS) and
reflux symptom score(RSS) respectively before and after treatment. Those who had
an abnormal pH study (pH <4 in the distal esophagus for >5% of the time)
underwent anti-GER treatment with lifestyle changes, and a proton pump inhibitor
(omeprazole 40 mg, bid) for 3 months. Asthma medications were added or deleted
based on severity of asthma. RESULTS: Out of 250 asthmatic patients screened,
forty patients fulfilled the inclusion criteria. Twenty eight of 40 patients(70%)
were diagnosed to have GERD. Of the patients 28 with GER, 8 patients(28.5%) had
no reflux symptoms. On 24 hr pH metry, the percentage time pH <4.0 was 10.81 +/-
4.72 and 1.11 +/- 1.21; Deemester score was 37.65 +/- 14.54 and 4.89 +/- 6.39 (p
value is 0.0001) in GERD and non-GERD patients respectively.In GERD group, post
treatment reflux symptom score(RSS) improved from 22.39 +/- 14.99 to 1.04 +/-
1.07, pulmonary symptom score(PSS) improved from 27.14 +/- 7.49 to 13.82 +/- 4.21
and night time asthma symptom score(NASS) improved from 6.71 +/- 1.80 to 3.04 +/-
1.23 (p-value <0.0001). After treatment, FEV1 and PEFR increased from 1.38 +/-
0.57 and 4.14 +/- 1.97 to 1.47 +/- 0.54 and 5.56 +/- 1.72, respectively (p-value
0.00114). CONCLUSIONS: PPI therapy improves nocturnal asthma symptoms, daytime
asthma symptoms, pulmonary function and decreases requirement of asthma
medications in these patients.
PMID- 25121370
TI - Giambattista Canano and his myology.
AB - Giambattista Canano was a sixteenth century Italian anatomist and physician. He
was educated at the University of Ferrara where, upon graduation, he was
appointed professor of anatomy. While at the university, Canano carried out a
pioneering study of skeletal muscles. This study was to be published in a multi
volumed book entitled Musculorum Humani Corporis Picturata Dissectio. However,
only the section on the muscles of the upper limb was published, as Canano
stopped the printing of his book. It is hypothesized that he met Vesalius at the
time and saw the proofs of his Fabrica which he assessed as far superior and,
consequently, decided to abort his project. The preserved copies of the
Dissectio, however, show that the standards of Canano's work surpassed most of
the anatomical studies published up to that time. Canano subsequently left the
academic position and made a notable career as a physician. His appointments
included prestigious positions of physician to the Pope and protomedicus of the
House of Este in Ferrara.
PMID- 25121371
TI - Pioglitazone: Hype and hope.
PMID- 25121372
TI - Hoover's sign: Clinical relevance in Neurology.
AB - Hoover's sign was described by Dr. Charles Franklin Hoover more than 100 years
back to differentiate between the organic and functional weakness of pyramidal
origin. This test is usually performed in the lower limbs and is valuable when on
bedside one is not sure about the nature of hemiparesis. A subject with
hemiparesis of organic cause while asked to flex the hip of normal leg against
resistance will not exert pressure on the hand of examiner placed under the heel
on the affected side while in hysterical weakness heightened pressure will be
felt on the examiner's hand. The presumed genesis of this sign could be the
crossed extensor reflex or the principle of synergistic contraction. It is a
useful clinical test in differentiating functional and organic paresis with
moderate sensitivity (63%) and high specificity (100%), but there are some
limitations which should be kept in mind while evaluating a patient.
PMID- 25121373
TI - Bedaquiline: a novel antitubercular drug for multidrug-resistant tuberculosis.
AB - Multidrug-resistant and extensively drug-resistant tuberculosis (TB) are emerging
global health threats. Bedaquiline is a new antituberculous drug belonging to the
diarylquinoline class that efficiently inhibits the adenosine triphosphate
synthase enzyme of Mycobacterium tuberculosis. It is a bactericidal and long
acting drug. It inhibits both dormant as well as replicating bacterial sub
populations and thus shortens the duration of TB treatment. This drug has been
approved by the Food and Drug Administration in December 2012 for the management
of multidrug resistant-TB. The drug marks the introduction of a new addition to
the TB armamentarium after four decades.
PMID- 25121374
TI - Telomeres and telomerase: understanding basic structure and potential new
therapeutic strategies targeting it in the treatment of cancer.
AB - The impact of cancer on humanity is huge and a great deal of research is going on
worldwide to find novel therapeutic targets. Telomerase is one such exciting
target. Increased telomerase activity provides cancer cells with unlimited
proliferative potential and is one of the hallmarks of cancer. This article
provides a basic understanding of telomere and telomerase in cancer and
summarizes various potential therapeutic approaches used for strategic targeting
of telomerase enzyme. Medline, Medscape, EMBASE, Cochrane database, Scopus and
clinicaltrials.gov were searched using terms like "telomeres", "telomerase" and
"targeted cancer therapy". Journal articles published from 2005 to 2013
describing telomerase-based cancer therapy were screened.
PMID- 25121375
TI - Arthritis, a complex connective and synovial joint destructive autoimmune
disease: animal models of arthritis with varied etiopathology and their
significance.
AB - Animal models play a vital role in simplifying the complexity of pathogenesis and
understanding the indefinable processes and diverse mechanisms involved in the
progression of disease, and in providing new knowledge that may facilitate the
drug development program. Selection of the animal models has to be carefully
done, so that there is morphologic similarity to human arthritic conditions that
may predict as well as augment the effective screening of novel antiarthritic
agents. The review describes exclusively animal models of rheumatoid arthritis
(RA) and osteoarthritis (OA). The development of RA has been vividly described
using a wide variety of animal models with diverse insults (viz. collagen,
Freund's adjuvant, proteoglycan, pristane, avridine, formaldehyde, etc.) that are
able to simulate/trigger the cellular, biochemical, immunological, and histologic
alterations, which perhaps mimic, to a great extent, the pathologic conditions of
human RA. Similarly, numerous methods of inducing animal models with OA have also
been described (such as spontaneous, surgical, chemical, and physical methods
including genetically manipulated animals) which may give an insight into the
events of alteration in connective tissues and their metabolism (synovial
membrane/tissues along with cartilage) and bone erosion. The development of such
arthritic animal models may throw light for better understanding of the
etiopathogenic mechanisms of human arthritis and give new impetus for the drug
development program on arthritis, a crippling disease.
PMID- 25121376
TI - Age appropriate screening for cancer: evidence-based practice in the United
States of America.
AB - Cancer screening is a well established and integral part of routine care in the
Western world including United States. Men and women are recommended to get age
specific screening for common cancers like breast, cervical, prostate, and colon.
The goal of screening is primary and secondary prevention. Cancer prevention and
early detection of cancers has been shown to improve survival rates and decrease
mortality by prompt appropriate treatment. This article serves to outline the
current guidelines in the United States for cancer screening and the evidence for
them as well as discusses the possibility of a similar model of care in India as
well as barriers to such a screening program for cancer. The evidence was mostly
obtained from systematic reviews done by the United States Preventive Services
Task Force guidelines and other peer institutions like American Cancer Society
and Agency for Healthcare Research and Quality.
PMID- 25121377
TI - Laron syndrome.
PMID- 25121378
TI - Needle in a haystack: Intraoperative breakage of pediatric minimal access surgery
instruments.
AB - The search for tiny bits of broken pediatric minimal access surgery (MAS)
instruments in an operative field is akin to the search for a needle in a
haystack. With the extension of MAS to the pediatric age group, instruments are
becoming smaller and equitably more prone to breakage. When breakages occur,
retrieval, especially in the pediatric abdominal cavity, can be challenging.
Inability to do so would affect patient safety and also lead to a web of medico
legal and ethical issues. We present two cases of intraoperative breakage: An
eyeless 3-0 polyamide suture needle and a 2-mm grasper blade both of which were
successfully retrieved and fortuitously escaped becoming retained surgical items.
PMID- 25121379
TI - Dengue infection presenting as acute hypokalemic quadriparesis.
AB - Dengue infection is one of the most common viral hemorrhagic fevers seen in the
tropical countries, including India. Its presentation varies from an acute self
resolving febrile illness to life-threatening hemorrhagic shock and multiorgan
dysfunction leading to death. Neurological presentations are uncommon and limited
to case reports only. Most common neurological manifestations being encephalitis,
acute inflammatory demyelinating polyradiculoneuropathy, transverse myelitis, and
acute disseminated encephalomyelitis.Hypokalemic quadriparesis as a presenting
feature of dengue is extremely rare. Here, we report this case of a 33-year-old
female, who presented with hypokalemic quadriparesis and was subsequently
diagnosed as dengue infection.
PMID- 25121380
TI - Hyperparathyroidism complicating pregnancy: a diagnostic challenge?
AB - Primary hyperparathyroidism (PHPT) is a rare etiology of hypercalcemia-induced
pancreatitis, contributing about 0.4% to 1.5% of cases in the general population
and up to 13% of cases during pregnancy. PHPT that occurs during pregnancy is a
challenging diagnosis as the physiological changes in calcium homeostasis mask
the symptoms of hypercalcemia. PHPT during pregnancy often remains undiagnosed
and untreated, and may result in serious clinical implications for the mother and
fetus. Most clinicians consider surgery within the second trimester of pregnancy
as the treatment of choice in this group of patients. This article refers to a
case of a 24-year married woman in whom PHPT was diagnosed for the first time in
postpartum period. She succumbed to complications on Day 20 postpartum.
Pathological findings revealed metastatic calcification in lungs, pancreas and
uterine vessels, chronic pancreatitis and renal cortical necrosis.
PMID- 25121381
TI - Chanarin-Dorfman syndrome: clinical report and novel mutation in ABHD5 gene.
AB - Chanarin-Dorfman syndrome (CDS) is a multisystem, autosomal recessive genetic
disorder characterized by congenital non-bullous ichthyosiform erythroderma with
accumulation of lipid droplets in granulocytes and basal keratinocytes. An 18
month-old female child presented with typical dermatological features of CDS. She
was born as a collodion baby. Liver biopsy showed micronodular cirrhosis along
with macrovesicular hepatic steatosis. Sequencing of all exons and exon-intron
boundaries of the ABHD5 gene showed that the patient was homozygous for a novel
mutation g.24947delG (c.773 + 1delG) in intron 5. This is the first Indian child
with mutation proven CDS.
PMID- 25121382
TI - Subcutaneous panniculitis like T cell lymphoma associated with erythromelalgia.
AB - Erythromelalgia is a rare disorder that simulates a small fiber neuropathy and
patients often have painful erythematous extremities during episodes. It is of
two types: A primary or inherited form that is sometimes associated with a Na
channel mutation or a secondary disorder associated with an underlying systemic
disorder. We present a 19-year-old boy who presented to us with erythromelalgia
and a febrile illness with systemic rash. Detailed work-up revealed another
unusual condition: Subcutaneous panniculitis like T cell lymphoma (SPTCL). This
is the first report of an association of erythromelalgia with SPTCL.
PMID- 25121383
TI - Hyperkalemia induced pseudo-myocardial infarction in septic shock.
AB - Hyperkalemia is an acute life-threatening disorder presenting to the emergency
department. Patients with hyperkalemia may manifest characteristic
electrocardiographic changes including tented T waves, widening of the QRS
complex and loss of P waves, sine wave pattern and eventually asystole. There
have been only few reports of hyperkalemia causing ST segment elevation on
electrocardiogram simulating an acute myocardial infarction. This case describes
pseudo-myocardial infarction due to hyperkalemia and septic shock. Rapid
determination of serum potassium levels by bedside blood gas analyzers serves to
be a useful guide. ST segment elevation related to hyperkalemia will resolve with
successful reduction of the serum potassium levels by appropriate therapy. It is
important for physicians to be aware of this condition as this will aid in
initiating correct therapy and prevent the patient from unnecessary interventions
and the associated risk of complications.
PMID- 25121384
TI - An unusual complication of stroke thrombolysis.
PMID- 25121385
TI - Understanding correlation in the context of outliers.
PMID- 25121387
TI - Esophageal perforation and death following glyphosate poisoning.
PMID- 25121386
TI - Impact of midday meals- have all variables been considered?
PMID- 25121388
TI - Paediatric malignant peripheral nerve sheath tumor with osteoid,
rhabdomyosarcomatous, and liposarcomatous differentiation.
PMID- 25121389
TI - Scalp hematoma: an atypical presentation of neurofibromatosis and a cause of
hemorrhagic shock.
PMID- 25121390
TI - Internal jugular vein medial to carotid artery.
PMID- 25121392
TI - Pure yolk sac tumor of testis in an adult: a rare occurrence.
PMID- 25121391
TI - Valgus deformity caused by dysplasia epiphysealis hemimelica in the knee.
PMID- 25121393
TI - Dr. Vidya Acharya.
PMID- 25121396
TI - Impairments due to injury, United States-1971.
AB - During 1971 there were an estimated 12.5 million impairments of various types
caused by injury based on data reported in the Health Interview Survey of the
civilian population not confined to institutions. An impairment is a chronic or
permanent defect, disabling or not, representing for the most part decrease or
loss of ability to perform certain functions, particularly those of the
musculoskeletal system and special senses. The originating cause, or etiology, is
obtained for each impairment reported in the interview. Based on data collected
in 1971 there were an estimated 51.1 million impairments reported in household
interviews in response to the list of impairments on the questionnnaire or in
response to questions about conditions causing disability or medical attention,
of which 24.6 percent were reported as having been caused by injury. The report,
"Impairments Due to Injury by Class and Type of Accident, United States, July
1959-June 1961," (Series 10, No. 6) presented data quite similar to that in the
present report. Among the 12.5 million impairments due to injury the most
frequently reported type was impairment of back or spine (except paralysis) with
an estimated prevalence of 3.1 million cases The second most frequently reported
type was impairment of lower extremity or hip (except paralysis or absence) with
an estimate of 2.7 million. An estimated 29.3 percent of all impairments due to
injury caused some degree of limitation of activity. About 25.4 percent of all
impairments due to injury resulted from accidents in the home; 29.3 percent
resulted from- injury occurring while at work; 17.8 percent resulted from moving
motor vehicle accidents; and 20 percent resulted from some type of fall.
PMID- 25121394
TI - Efficacy of electronic portable assistive devices for people with acquired brain
injury: a systematic review.
AB - A systematic review was conducted to evaluate the efficacy of electronic portable
assistive devices (EPADs) for people with acquired brain injury. A systematic
database search (OVID, CINAHL) found 541 citations published between 1989 and the
end of 2012. A total of 23 reports met the inclusion/exclusion criteria, namely
intervention studies (group, n-of-1) testing the efficacy of EPADs as
compensatory devices for cognitive impairment for people with acquired brain
injury aged 16-65 years. Study quality was rated by the PEDro (Physiotherapy
Evidence Database) scale, (randomised controlled trials), the Downes and Black
tool (other group intervention studies), and the Single Case Experimental Design
tool (single participant studies). Levels of evidence were determined using five
levels of classification based on the Spinal Cord Injury Rehabilitation Evidence
table. Results found no Level 1 studies (RCTs with PEDro score >= 6), four Level
2 studies and 10 Level 3 studies. There was insufficient evidence to recommend
any practice standards, but sufficient evidence to recommend the use of
electronic reminder systems in supporting the everyday functioning of people with
acquired brain injury as a practice guideline. Higher quality studies are
required to support a broader range of compensatory roles that EPADs have the
potential to play in neurorehabilitation and the long-term support of people with
acquired brain injury.
PMID- 25121395
TI - Design, synthesis, and evaluation of multitarget-directed selenium-containing
clioquinol derivatives for the treatment of Alzheimer's disease.
AB - A series of selenium-containing clioquinol derivatives were designed,
synthesized, and evaluated as multifunctional anti-Alzheimer's disease (AD)
agents. In vitro examination showed that several target compounds exhibited
activities such as inhibition of metal-induced Abeta aggregation, antioxidative
properties, hydrogen peroxide scavenging, and the prevention of copper redox
cycling. A parallel artificial membrane permeation assay indicated that selenium
containing clioquinol derivatives possessed significant blood-brain barrier (BBB)
permeability. Compound 8a, with a propynylselanyl group linked to the oxine,
demonstrated higher hydrogen peroxide scavenging and intracellular antioxidant
activity than clioquinol. Furthermore, 8a exhibited significant inhibition of
Cu(II)-induced Abeta1-42 aggregation and was capable of disassembling the
preformed Cu(II)-induced Abeta aggregates. Therefore, 8a is an excellent
multifunctional promising compound for development of novel drugs for AD.
PMID- 25121398
TI - A new entry to asymmetric platinum(IV) complexes via oxidative chlorination.
AB - Pt(IV) complexes are usually prepared by oxidation of the corresponding Pt(II)
counterparts, typically using hydrogen peroxide or chlorine. A different way to
synthesize asymmetrical Pt(IV) compounds is the oxidative chlorination of Pt(II)
counterparts with N-chlorosuccinimide. The reaction between cisplatin cis
[PtCl2(NH3)2], carboplatin, cis-[PtCl2(dach)] and cis-[Pt(cbdc)(dach)] (cbdc =
cyclobutane-1,1'-dicarboxylato; dach = cyclohexane-1R,2R-diamine) with N
chlorosuccinimide in ethane-1,2-diol was optimized to produce the asymmetric
Pt(IV) octahedral complexes [PtA2Cl(glyc)X2] (A2 = 2 NH3 or dach; glyc = 2
hydroxyethanolato; X2 = 2 Cl or cbdc) in high yield and purity. The X-ray crystal
structure of the [Pt(cbdc)Cl(dach)(glyc)] complex is also reported. Moreover, the
oxidation method proved to be versatile enough to produce other mixed Pt(IV)
derivatives varying the reaction medium. The two trichlorido complexes easily
undergo a pH-dependent hydrolysis reaction, whereas the dicarboxylato compounds
are stable enough to allow further coupling reactions for drug targeting and
delivery via the glyc reactive pendant. Therefore, the coupling reaction between
the [Pt(cbdc)Cl(dach)(glyc)] and a model carboxylic acid, a model amine, and
selectively protected amino acids is reported.
PMID- 25121397
TI - ProSeal Laryngeal Mask Airway Attenuates Systemic and Cerebral Hemodynamic
Response During Awakening of Neurosurgical Patients: A Randomized Clinical Trial.
AB - BACKGROUND: Extubation and emergence from anesthesia may lead to systemic and
cerebral hemodynamic changes that endanger neurosurgical patients. We aimed to
compare systemic and cerebral hemodynamic variables and cough incidence in
neurosurgery patients emerging from general anesthesia with the standard
procedure (endotracheal tube [ETT] extubation) or after replacement of the ETT
with a laryngeal mask airway (LMA). MATERIALS AND METHODS: Forty-two patients
undergoing supratentorial craniotomy under general anesthesia were included in a
randomized open-label parallel trial. Patients were randomized (sealed envelopes
labeled with software-generated randomized numbers) to awaken with the ETT in
place or after its replacement with a ProSeal LMA. We recorded mean arterial
pressure as the primary endpoint and heart rate, middle cerebral artery flow
velocity, regional cerebral oxygen saturation, norepinephrine plasma
concentrations, and coughing. RESULTS: No differences were found between groups
at baseline. All hemodynamic variables increased significantly from baseline in
both groups during emergence. The ETT group had significantly higher mean
arterial pressure (11.9 mm Hg; 95% confidence interval [CI], 2.1-21.8 mm Hg)
(P=0.017), heart rate (7.2 beats/min; 95% CI, 0.7-13.7 beats/min) (P=0.03), and
rate-pressure product (1045.4; 95% CI, 440.8-1650) (P=0.001). Antihypertensive
medication was administered to more ETT-group patients than LMA-group patients (9
[42.9%] vs. 3 [14.3%] patients, respectively; P=0.04). The percent increase in
regional cerebral oxygen saturation was greater in the ETT group by 26.1% (95%
CI, 9.1%-43.2%) (P=0.002), but no between-group differences were found in MCA
flow velocity. Norepinephrine plasma concentrations rose in both groups between
baseline and the end of emergence: LMA: from 87.5+/-7.1 to 125.6+/-17.3 pg/mL;
and ETT: from 118.1+/-14.1 to 158.1+/-24.7 pg/mL (P=0.007). The differences
between groups were not significant. The incidence of cough was higher in the ETT
group (87.5%) than in the LMA group (9.5%) (P<0.001). CONCLUSIONS: Replacing the
ETT with the LMA before neurosurgical patients emerge from anesthesia results in
a more favorable hemodynamic profile, less cerebral hyperemia, and a lower
incidence of cough.
PMID- 25121399
TI - Effects of mycoplasmal upper-respiratory-tract disease on movement and
thermoregulatory behavior of gopher tortoises (Gopherus polyphemus) in Georgia,
USA.
AB - Abstract From 2011-12, we studied a gopher tortoise (Gopherus polyphemus)
population with a historically high prevalence of antibodies to Mycoplasma
agassizii to assess long-term effects of upper-respiratory-tract disease (URTD)
on tortoise behavior. We radiotracked 30 adult tortoises (16 males, 14 females)
from a long-term study site with the use of mark-recapture methods to determine
site fidelity and to compare home-range size to that of a study in 1997. An
additional 10 tortoises (six males, four females) with severe clinical signs of
URTD from elsewhere in the study area were radiotracked and compared to tortoises
that were asymptomatic or had only mild clinical signs. We also monitored
thermoregulatory behavior of tortoises with the use of data loggers affixed to
the carapace. There was no significant difference in home-range size between the
asymptomatic tortoises and those with mild symptoms. Home ranges of tortoises
with severe URTD were significantly larger than asymptomatic or mildly affected
tortoises. Tortoises with severe clinical signs moved long distances over short
periods, contradicting a hypothesis that chronically infected tortoises are less
likely to emigrate. Prevalence of M. agassizii antibodies was similar among the
three groups (98% overall), but prevalence of antibodies to a second pathogen
associated with URTD, Mycoplasma testudineum, was lower in the asymptomatic
(n=14, 7%) and mild-symptoms (n=7, 14%) groups than the severe-symptoms group
(n=8, 50%). Variation in the average carapacial temperatures of tortoises with
severe URTD was significantly different from carapacial temperatures of mild and
asymptomatic tortoises, suggesting differences in thermoregulatory behavior of
severely ill tortoises. Our 15-yr recapture data suggest that, despite high
prevalence of M. agassizii, population density has not decreased over time.
However, emigration, especially of tortoises with severe clinical disease, may
play an important role in dispersal and persistence of pathogens.
PMID- 25121400
TI - Molecular methods to detect Mycoplasma spp. And Testudinid herpesvirus 2 in
desert tortoises (Gopherus agassizii) and implications for disease management.
AB - Abstract Mycoplasmas are an important cause of upper respiratory tract disease
(URTD) in desert tortoises (Gopherus agassizii) and have been a main focus in
attempts to mitigate disease-based population declines. Infection risk can vary
with an animal's population of origin, making screening tests popular tools for
determining infection status in individuals and populations. To provide
additional methods for investigating URTD we developed quantitative PCR (qPCR)
assays specific for agents causing clinical signs of URTD: Mycoplasma agassizii,
Mycoplasma testudineum, and Testudinid herpesvirus 2 (TeHV2) and tested
necropsied desert tortoises housed at the Desert Tortoise Conservation Center in
Las Vegas, Nevada, USA, as well as wild desert tortoises (n=3), during 2010.
Findings were compared with M. agassizii enzyme-linked immunosorbent assay
(ELISA) data. Based on qPCR, the prevalence of M. agassizii was 75% (33/44) and
the prevalence of TeHV2 was 48% (20/42) in the evaluated population. Both agents
were also present in the wild tortoises. Mycoplasma testudineum was not detected.
The M. agassizii ELISA and qPCR results did not always agree. More tortoises were
positive for M. agassizii by nasal mucosa testing than by nasal flush. Our
findings suggest that mycoplasmas are not the only agents of concern and that a
single M. agassizii ELISA or nasal flush qPCR alone failed to identify all
potentially infected animals in a population. Caution should be exercised in
using these tests for disposition decisions.
PMID- 25121401
TI - Baseline cutaneous bacteria of free-living New Zealand native frogs (Leiopelma
archeyi and Leiopelma hochstetteri) and implications for their role in defense
against the amphibian chytrid (Batrachochytrium dendrobatidis).
AB - Abstract Knowledge of baseline cutaneous bacterial microbiota may be useful in
interpreting diagnostic cultures from captive sick frogs and as part of
quarantine or pretranslocation disease screening. Bacteria may also be an
important part of innate immunity against chytridiomycosis, a fungal skin disease
caused by Batrachochytrium dendrobatidis (Bd). In February 2009, 92 distinct
bacterial isolates from the ventral skin of 64 apparently healthy Leiopelma
archeyi and Leiopelma hochstetteri native frogs from the Coromandel and
Whareorino regions in New Zealand were identified using molecular techniques. The
most-common isolates identified in L. archeyi were Pseudomonas spp. and the most
common in L. hochstetteri were Flavobacterium spp. To investigate the possible
role of bacteria in innate immunity, a New Zealand strain of Bd (Kaikorai Valley
Lewingii-2008-SDS1) was isolated and used in an in vitro challenge assay to test
for inhibition by bacteria. One bacterial isolate, a Flavobacterium sp.,
inhibited growth of Bd. These results imply that diverse cutaneous bacteria are
present and may play a role in the innate defense in Leiopelma against pathogens,
including Bd, and are a starting point for further investigation.
PMID- 25121402
TI - Are passerine birds reservoirs for influenza A viruses?
AB - Abstract Although peridomestic passerine species have been involved in influenza
A virus (IAV) outbreaks in poultry, there is little evidence to indicate they
serve as reservoirs for these viruses under natural conditions. Recent molecular
based detections of IAV in terrestrial wild birds have challenged this paradigm,
and it has been suggested that additional research is warranted to better define
the role of these birds as IAV hosts. To address this need, we reviewed the
published literature reporting results from IAV surveillance of passerines. We
also conducted prospective virologic and serologic surveillance of North American
passerines for IAVs. The literature review included 60 publications from 1975
2013 that reported results from 829 species of passerines and other terrestrial
birds. In our prospective study during 2010 and 2011, 3,868 serum samples and 900
swab samples were collected and tested from 102 terrestrial wild bird species
from Georgia, New Jersey, Delaware, and Minnesota, USA. Antibodies to the
nucleoprotein of IAV were detected with a commercial blocking enzyme-linked
immunosorbent assay in 4/3,868 serum samples (0.1%); all positive samples were
from Minnesota. No virus was detected in 900 swab samples by virus isolation in
embryonated chicken eggs or matrix real-time reverse transcriptase PCR. Our
results are consistent with historic literature; although passerines and
terrestrial wild birds may have a limited role in the epidemiology of IAV when
associated with infected domestic poultry or other aberrant hosts, there is no
evidence supporting their involvement as natural reservoirs for IAV.
PMID- 25121403
TI - An alternative interpretation of plasma selenium data from endangered patagonian
huemul deer (Hippocamelus bisulcus).
PMID- 25121405
TI - Aprocta cylindrica (Nematoda) infection in a European Robin (Erithacus rubecula)
in Britain.
AB - A European Robin (Erithacus rubecula) found dead in England had marked
blepharitis and periocular alopecia associated with Aprocta cylindrica (Nematoda:
Aproctidae) and concurrent mixed fungal infections. Aprocta cylindrica should be
considered a differential diagnosis in periocular abnormalities of robins and
other insectivorous, migratory passerines in Western Europe.
PMID- 25121406
TI - European mustelids occupying pristine wetlands in the Danube Delta are infected
with Trichinella likely derived from domesticated swine.
AB - Abstract We analyzed 32 specimens from nine species of Mustelidae for
Trichinella; six infections from two Trichinella species were observed from three
host species. This provides documentation of Trichinella in Mustela erminea and
Martes foina in Romania and Trichinella spiralis in a mustelid host from Europe.
Trichinella spiralis continues to be a public challenge characterized by a wide
host range and geographical distribution ( Pozio 2007 ). During the past 20 yr,
Romania has had the most reported human cases of trichinellosis in the world (
Blaga et al. 2007 ). Transmission occurs among domesticated swine, rats, and wild
mammals that feed by scavenging or predation ( Pozio 2000 ). Trichinella
transmission to humans may occur by consumption of meat of livestock infected
after exposure to wildlife ( Pozio et al. 2009 ).
PMID- 25121404
TI - Novel combinations of nalbuphine and medetomidine for wildlife immobilization.
AB - We formulated novel drug combinations of nalbuphine HCl and medetomidine HCl
(NalMed), with or without azaperone tartrate, for use in immobilizing Rocky
Mountain elk (Cervus elaphus nelsoni) and potentially for other wildlife species.
Using the lowest tested nalbuphine dose (0.3 mg/kg) that produced sedation in
elk, we initially evaluated a combination of nalbuphine, medetomidine, and
azaperone (NalMed-A) for immobilizing adult elk. Based on initial success, we
then conducted follow-up trials to assess alternative NalMed formulations
successively modified to improve field usability, striving to shorten induction
within a dose volume that accommodated practical remote delivery. All NalMed
formulations immobilized adult elk; however, combinations with dose volumes that
included about 80 mg nalbuphine tended to yield the shortest inductions (mean 6.8
min with, and 7.7 min without, azaperone). Our findings demonstrate that
nalbuphine and medetomidine can be combined to yield effective, low-volume (<= 2
mL), lightly regulated, reversible drug combinations. Based on results to date,
we recommend NalMed-A (40 mg/mL nalbuphine, 10 mg/mL medetomidine, and 10 mg/mL
azaperone) dosed at 1.8-2.0 mL for immobilizing adult elk; for recovery we
recommend 50 mg naltrexone and 600 mg tolazoline administered intramuscularly
(IM) about 5 min in advance of 100 mg atipamezole (divided 25 mg intravenously
and 75 mg IM). Further work is under way to explore efficacy in other large
mammal species.
PMID- 25121407
TI - Pathogen infection and exposure, and ectoparasites of the federally endangered
Amargosa vole (Microtus californicus scirpensis), California, USA.
AB - Abstract We surveyed pathogens and ectoparasites among federally endangered
Amargosa voles (Microtus californicus scirpensis) and sympatric rodents in Tecopa
Hot Springs, Inyo County, California, December 2011-November 2012. We aimed to
assess disease and detect possible spillover from or connectivity with other
hosts within and outside the Amargosa ecosystem. We assessed 71 individual voles
and 38 individual sympatric rodents for current infection with seven vector-borne
zoonotic pathogens and past exposure to five pathogens. Thirteen percent of
Amargosa voles were PCR positive for Toxoplasma gondii, a zoonotic protozoan that
may alter host behavior or cause mortality. Additionally, we found antibodies
against Borrelia burgdorferi sensu lato (SL) spp. in 21% of voles, against
Anaplasma phagocytophilum in 2.6%, Rickettsia spp. in 13%, relapsing fever
Borrelia (3.9%), and T. gondii (7.9%). Sympatric rodents also had active
infections with Borrelia SL spp. (15%). Of the ectoparasites collected, the tick
Ixodes minor is of particular interest because the study area is well outside of
the species' reported range and because I. minor ticks infest migratory birds as
well as rodents, showing a potential mechanism for pathogens to be imported from
outside the Amargosa ecosystem.
PMID- 25121408
TI - Serologic survey for cross-species pathogens in urban coyotes (Canis latrans),
Colorado, USA.
AB - Abstract As coyotes (Canis latrans) adapt to living in urban environments, the
opportunity for cross-species transmission of pathogens may increase. We
investigated the prevalence of antibodies to pathogens that are either zoonotic
or affect multiple animal species in urban coyotes in the Denver metropolitan
area, Colorado, USA, in 2012. We assayed for antibodies to canine parvovirus-2,
canine distemper virus, rabies virus, Toxoplasma gondii, Yersinia pestis, and
serotypes of Leptospira interrogans. Overall, 84% of the animals had antibodies
to canine parvovirus-2, 44% for canine distemper virus, 20% for T. gondii (IgG),
28% for Y. pestis, and 4% for L. interrogans serotype Grippotyphosa. No
neutralizing antibodies were detected to rabies virus, T. gondii (IgM), or L.
interrogans serotypes other than Grippotyphosa. With 88% of animals exposed to at
least one pathogen, our results suggest that coyotes may serve as important
reservoirs and sentinels for etiologic agents.
PMID- 25121410
TI - Detection and molecular characterization of a reovirus in black-capped chickadees
(Poecile atricapillus) from Minnesota, USA.
AB - In 2011, the Minnesota Rehabilitation Center submitted four dead Black-capped
Chickadees (Poecile atricapillus) for necropsy to the Minnesota Veterinary
Diagnostic Laboratory. All four chickadees were underweight and dehydrated and
their intestinal contents were watery and yellowish. No significant lesions were
observed upon histopathologic examination. Viral particles of the family
Reoviridae were detected after negative-contrast electron microscopic examination
of intestinal contents. Analysis by reverse transcriptase PCR and sequencing
confirmed the presence of a reovirus. Based on phylogenetic analysis, the
chickadee reovirus had 97.1% to 98.3% and 89.4% to 97.8% nucleotide identity with
turkey enteric reoviruses from apparently healthy and enteritis-affected turkey
poults, respectively. The chickadee reovirus had only 56.5% and 58.5% nucleotide
and 54.5% and 56.8% amino acid identity with psittacine reovirus and Tvarminne
avian virus, respectively. These results indicate that the chickadee reovirus is
closely related to turkey reoviruses.
PMID- 25121409
TI - Relatively high prevalence of pox-like lesions in Henslow's sparrow (Ammodrammus
henslowii) among nine species of migratory grassland passerines in Wisconsin,
USA.
AB - Globally, Avipoxvirus species affect over 230 species of wild birds and can
significantly impair survival. During banding of nine grassland songbird species
(n=346 individuals) in southwestern Wisconsin, USA, we noted species with a 2-6%
prevalence of pox-like lesions (possible evidence of current infection) and 4-10%
missing digits (potential evidence of past infection). These prevalences approach
those recorded among island endemic birds (4-9% and 9-20% for the Galapagos and
Hawaii, respectively) for which Avipoxvirus species have been implicated as
contributing to dramatic population declines. Henslow's Sparrow Ammodramus
henslowii (n=165 individuals) had the highest prevalence of lesions (6.1%) and
missing digits (9.7%). Among a subset of 26 Henslow's Sparrows from which blood
samples were obtained, none had detectable antibody reactive to fowlpox virus
antigen. However, four samples (18%) had antibody to canarypox virus antigen with
test sample and negative control ratios (P/N values) ranging from 2.4 to 6.5
(median 4.3). Of four antibody-positive birds, two had lesions recorded (one was
also missing a digit), one had digits missing, and one had no signs.
Additionally, the birds with lesions or missing digits had higher P/N values than
did the antibody-positive bird without missing digits or recorded lesions. This
study represents an impetus for considering the impacts and dynamics of disease
caused by Avipoxvirus among North American grassland bird species.
PMID- 25121411
TI - Rabies in the insectivorous Pallas's mastiff bat (Molossus molossus) in
northeastern Brazil.
AB - We describe the pathologic and immunohistochemical findings in five cases of
rabies in the insectivorous Pallas's mastiff bat (Molossus molossus) in the city
of Patos, state of Paraiba, northeastern Brazil. All cases were found during the
day, in different neighborhoods, prostrate and unable to fly. No significant
lesions were observed at necropsy or on histologic examination. The brains of the
five bats showed strong immunohistochemical labeling for rabies virus in the form
of large corpuscles or multiple clusters of granules within the perikarya of
neurons in different areas of the brain, mainly in the cerebral cortex and
cerebellar Purkinje cells. Three bats tested by direct immunofluorescence and
mouse inoculation were also positive for rabies. These data demonstrate that M.
molossus may be infected with the rabies virus and develop rabies, even without
histologic lesions in the central nervous system, and can be a source of
infection for humans and domestic animals.
PMID- 25121412
TI - Asymmetric synthesis of chiral heterocyclic amino acids via the alkylation of the
Ni(II) complex of glycine and alkyl halides.
AB - An investigation into the reactivity profile of alkyl halides has led to the
development of a new method for the asymmetric synthesis of chiral heterocyclic
amino acids. This protocol involves the asymmetric alkylation of the Ni(II)
complex of glycine to form an intermediate, which then decomposes to form a
series of valuable chiral amino acids in high yields and with excellent
diastereoselectivity. The chiral amino acids underwent a smooth intramolecular
cyclization process to afford the valuable chiral heterocyclic amino acids in
high yields and enantioselectivities. This result paves the way for the
development of a new synthetic method for chiral heterocyclic amino acids.
PMID- 25121414
TI - Breast reconstruction and medical necessity.
PMID- 25121413
TI - Maximum standardized uptake value on 18F-fluoro-2-deoxy-glucose positron emission
tomography/computed tomography and glucose transporter-1 expression correlates
with survival in invasive ductal carcinoma of the pancreas.
AB - OBJECTIVES: The purpose of this study was to assess the correlations among the
maximum standardized uptake value (SUVmax) on 18F-fluoro-2-deoxy-glucose positron
emission tomography/computed tomography (FDG-PET/CT); the expressions of glucose
transporter 1 (GLUT-1), glucose transporter 3, and epidermal growth factor
receptor (EGFR); as well as prognosis in patients with invasive ductal carcinoma
of the pancreas. METHODS: A total of 41 patients with surgically resected and
histologically proven invasive ductal carcinoma of the pancreas who underwent
preoperative FDG-PET/CT were assessed. The SUVmax at the primary tumor site was
measured by FDG-PET/CT, and immunohistochemical staining of tumor sections was
performed for GLUT-1, glucose transporter 3, and EGFR. RESULTS: Higher FDG uptake
(SUVmax, >3.40) and GLUT-1 expression were significantly associated with shorter
overall survival (P < 0.05). The SUVmax was not found to be significantly
correlated with clinicopathological characteristics such as TNM classification,
lymph node metastasis, and tumor differentiation. The EGFR expression was
significantly correlated with the SUVmax (P = 0.024). CONCLUSIONS: Higher FDG
uptake and GLUT-1 expression in invasive ductal carcinoma of the pancreas seems
to be an important prognostic factor. In addition, the EGFR expression was
significantly correlated with the SUVmax.
PMID- 25121415
TI - Dakin's solution: historical perspective and current practice.
AB - Dakin's solution was first introduced by military physicians responding to the
challenges of treating artillery injuries in World War I. Administration was
personnel intensive, and at times unpredictable in the conditions of the
frontlines, but nonetheless the practice saved countless lives and limbs. Dakin's
solution remained the prevailing method for treating contaminated wounds until
the introduction of antibiotics during World War II. With the emergence of
antibiotic-resistant organisms in the 1980s, interest in antiseptic treatment of
wounds resurfaced; especially in chronic wounds, antiseptics once again saw
liberal use. However, as the understanding of wound healing advanced, focus
shifted from "prevention of infection" to "creation of an optimal environment for
the repair process." Concern that antiseptics could be toxic to the cells of the
repair process has led many to discontinue their use. Although such all-or-none
approaches might simplify the decision-making process, they fail to address the
complexity of optimal wound management. As recent research suggests, there may be
a renewed role for Dakin's solution.
PMID- 25121416
TI - Lessons learned from the first quadruple extremity transplantation in the world.
AB - BACKGROUND: Limb transplantation is emerging as a promising area of surgery and
is an indispensable alternative for prosthetic rehabilitation of amputees, the
severity of which is increasing because of combat-related injuries. Successful
unilateral and bilateral limb transplantations have already been performed before
this operation. METHODS: We performed the first ever quadruple limb
transplantation in February 2012. The limbs procured from a 40-year-old man heart
beating donor were transplanted to a 27-year-old male patient who was a quadruple
amputee for the last 14 years because of an electrical injury. RESULTS: To
shorten the ischemic period to a minimum, 3 separate microsurgery teams worked
simultaneously. All extremities were reperfused within 8 hours of procurement,
and the operation lasted for 12 hours. Metabolic load was managed by
hemodialysis. One hour after the completion of the operation, cardiac arrest
developed, resuscitation of which necessitated median sternotomy and temporary
partial cardiopulmonary support. Despite the removal of the transplanted limbs
and all efforts including continuous hemodialysis, plasmapheresis, and
extracorporeal membrane oxygenation, the patient died on the fourth day after
transplantation in a clinical condition of severe systemic inflammation.
CONCLUSIONS: The problems we faced were difficulty of vascular access for
invasive monitoring and fluid replacement, and the severe systemic inflammation
effects of which could not be dealt with, despite aggressive supportive
treatment. We hope that our experience will enlighten the surgeons who are
willing to extend the limits of limb transplantation and serve the success of
future operations.
PMID- 25121417
TI - Discussion of lessons learned from the first quadruple extremity transplantation
in the world: the logic of massive allograft transplantation.
PMID- 25121418
TI - Congenital nail abnormalities: a review of the literature.
AB - Congenital nail abnormalities (CNAs) are rare conditions in which the nail tissue
appears abnormal compared with the fingers and the toes. They usually present
accompanying deformities and disorders. Our purpose was to review the current
literature on the clinical aspects of CNA. We reviewed the literature to evaluate
peer-reviewed articles on the topic. Detailed reports have characterized many
types of CNA. In this article, we provide a review of the literature based on the
current understanding of CNAs and the clinical varieties thereof.
PMID- 25121419
TI - The forehead flap for immediate reconstruction of the nose after bite injuries:
indications, advantages, and disadvantages.
PMID- 25121420
TI - Fat graft survival: physics matters: invited commentary to "The impact of
liposuction cannula size on adipocyte viability".
PMID- 25121421
TI - Applications of algorithmic differentiation to phase retrieval algorithms.
AB - In this paper, we generalize the techniques of reverse-mode algorithmic
differentiation to include elementary operations on multidimensional arrays of
complex numbers. We explore the application of the algorithmic differentiation to
phase retrieval error metrics and show that reverse-mode algorithmic
differentiation provides a framework for straightforward calculation of gradients
of complicated error metrics without resorting to finite differences or laborious
symbolic differentiation.
PMID- 25121422
TI - Characteristic functions describing the power absorption response of periodic
structures to partially coherent fields.
AB - Periodic thin-film structures are widely used as absorptive structures for
electromagnetic radiation. We show that the absorption behavior for partially
coherent illumination can be fully characterized by a set of characteristic
functions in wavenumber space. We discuss the prediction of these functions using
electromagnetic solvers based on periodic boundary conditions, and their
measurement experimentally using Energy Absorption Interferometry (EAI). The
theory is developed here for the case of 2D absorbers with TE illumination and
arbitrary material properties in the plane of the problem, except for the
resistivity, which is assumed isotropic. Numerical examples are given for the
case of absorbing strips printed on a semi-infinite substrate. We derive rules
for the convergence of the representation as a function of the number of
characteristic functions used, as well as conditions for sampling in EAI
experiments.
PMID- 25121423
TI - Compressed sampling strategies for tomography.
AB - We investigate new sampling strategies for projection tomography, enabling one to
employ fewer measurements than expected from classical sampling theory without
significant loss of information. Inspired by compressed sensing, our approach is
based on the understanding that many real objects are compressible in some known
representation, implying that the number of degrees of freedom defining an object
is often much smaller than the number of pixels/voxels. We propose a new approach
based on quasi-random detector subsampling, whereas previous approaches only
addressed subsampling with respect to source location (view angle). The
performance of different sampling strategies is considered using object
independent figures of merit, and also based on reconstructions for specific
objects, with synthetic and real data. The proposed approach can be implemented
using a structured illumination of the interrogated object or the detector array
by placing a coded aperture/mask at the source or detector side, respectively.
Advantages of the proposed approach include (i) for structured illumination of
the detector array, it leads to fewer detector pixels and allows one to integrate
detectors for scattered radiation in the unused space; (ii) for structured
illumination of the object, it leads to a reduced radiation dose for patients in
medical scans; (iii) in the latter case, the blocking of rays reduces scattered
radiation while keeping the same energy in the transmitted rays, resulting in a
higher signal-to-noise ratio than that achieved by lowering exposure times or the
energy of the source; (iv) compared to view-angle subsampling, it allows one to
use fewer measurements for the same image quality, or leads to better image
quality for the same number of measurements. The proposed approach can also be
combined with view-angle subsampling.
PMID- 25121424
TI - Generation of hollow beam with radially polarized vortex beam and complex
amplitude filter.
AB - The generation of hollow beams with a long focal depth from a radially polarized
Bessel-Gaussian beam with a second-order vortex phase and an amplitude filter is
theoretically investigated by Richards-Wolf's integral. The null intensity on the
optical axis is achieved by introducing the second-order vortex. The long focal
depth is a result of the amplitude filtering based on the cosine function and
Euler transformation. Numerical results indicate that the focal depth of a hollow
beam is improved from 0.96lambda to 2.28lambda with a slight increase of the
transverse size for the simplest amplitude filter design. The intensity
distribution twist phenomenon of the x- and y-polarized components around the
optical axis due to the introducing of the vortex phase is also discussed. It is
believed that the proposed scheme can be used to achieve particle acceleration
and optical trapping.
PMID- 25121425
TI - High-precision rotation angle measurement method based on monocular vision.
AB - To accurately measure the attitude angles (pitch, roll, and yaw) of a rigid
object that rotates in a space, we propose a high-precision rotation angle
measurement method based on monocular vision. This method combines camera self
calibration, multiview geometry, and 3D measurement. This monocular vision
measuring system consists of an area scan CCD, a prime lens, and a spots array
target, which are fixed on the measured object. We can calculate the rotation
angle according to the rebuilt rotating spots array target by using this
monocular vision measuring system. The measurement precision of rotation angle
can reach 1 arc sec in this paper's experiments. This method has high measurement
precision and good stability. Therefore we can widely use this method in
machinery manufacturing, engineering measurement, aerospace, and the military.
PMID- 25121426
TI - Computational aspects of the through-focus characteristics of the human eye.
AB - Calculating through-focus characteristics of the human eye from a single
objective measurement of wavefront aberration can be accomplished through a range
of methods that are inherently computationally cumbersome. A simple yet accurate
and computationally efficient method is developed, which combines the philosophy
of the extended Nijboer-Zernike approach with the radial-basis-function-based
approximation of the complex pupil function. The main advantage of the proposed
technique is that the increase of the computational cost for a vector-valued
defocus parameter is practically negligible in comparison to the corresponding
scalar-valued defocus parameter.
PMID- 25121427
TI - Diffraction by a frustrated system: the triangular Ising antiferromagnet.
AB - Expressions are derived for diffraction by the triangular Ising antiferromagnet,
a disordered lattice system consisting of two kinds of scatterer and exhibiting
geometric frustration. Analysis of the expressions shows characteristics of the
diffraction patterns, including the presence of Bragg and diffuse diffraction,
superlattice reflections, and their behavior with temperature. These
characteristics are illustrated by numerical simulations. The results have
application to diffraction imaging of disordered systems.
PMID- 25121428
TI - Optimization for calibration of large-scale optical measurement positioning
system by using spherical constraint.
AB - The measurement accuracy of a large-scale optical measurement positioning system
largely depends on the calibration procedure. A more reliable calibration
approach for the system by using spherical constraints is presented in this
paper, and both the adjustment model based on spherical constraint and the
calculation method for the optimization are given. This approach can provide
constraint in every direction of the system in the workspace and thereby estimate
the orientation parameters more accurately than by using current methods. The
experimental data show that by using the proposed method, which improves the
accuracy of the depth direction, the average 3D coordinate error of the system
compared with the laser tracker is about 0.18 mm in the whole workspace.
PMID- 25121429
TI - Quantitative analysis of imperfect frequency multiplying in fractional Talbot
planes and its effect on high-frequency-grating lithography.
AB - Fractional Talbot images of amplitude line gratings, with small opening slits
compared to the period, are characterized by an integer multiple of the gratings'
spatial frequency. We investigate the formation of fractional Talbot images
analytically within a scalar framework and give a comprehensible insight into the
paraxial limits involved. Particular attention is paid to nonparaxial effects on
the intensity distribution at fractional Talbot planes and their lateral
periodicities. We present a comparison between the measured intensity
distributions and a numerical implementation of our analytical method. Both ways
reveal the paraxial limits of frequency multiplication on fractional Talbot
images. The use of fractional Talbot images for lithography results in ghost
diffraction orders. We roughly estimate the ghost orders quantitatively with a
simple numerical model for monochromatic and polychromatic illumination.
PMID- 25121430
TI - Outlier modeling for spectral data reduction.
AB - The spectra in spectral reflectance datasets tend to be quite correlated and
therefore they can be represented more compactly using standard techniques such
as principal components analysis (PCA) as part of a lossy compression strategy.
However, the presence of outlier spectra can often increase the overall error of
the reconstructed spectra. This paper introduces a new outlier modeling (OM)
method that detects, clusters, and separately models outliers with their own set
of basis vectors. Outliers are defined in terms of the robust Mahalanobis
distance using the fast minimum covariance determinant algorithm as a robust
estimator of the multivariate mean and covariance from which it is computed.
After removing the outliers from the main dataset, the performance of PCA on the
remaining data improves significantly; however, since outlier spectra are a part
of the image, they cannot simply be ignored. The solution is to cluster the
outliers into a small number of clusters and then model each cluster separately
using its own cluster-specific PCA-derived bases. Tests show that OM leads to
lower spectral reconstruction errors of reflectance spectra in terms of both
normalized RMS and goodness of fit.
PMID- 25121431
TI - Combining local binary patterns and local color contrast for texture
classification under varying illumination.
AB - This paper presents a texture descriptor for color texture classification
specially designed to be robust against changes in the illumination conditions.
The descriptor combines a histogram of local binary patterns (LBPs) with a novel
feature measuring the distribution of local color contrast. The proposed
descriptor is invariant with respect to rotations and translations of the image
plane and with respect to several transformations in the color space. We
evaluated the proposed descriptor on the Outex test suite, by measuring the
classification accuracy in the case in which training and test images have been
acquired under different illuminants. The results obtained show that our
descriptor outperforms the original LBP approach and its color variants, even
when these are computed after color normalization. Moreover, it also outperforms
several other color texture descriptors in the state of the art.
PMID- 25121432
TI - Structural design and characteristics of dual-mode fibers with equalized group
velocity.
AB - We investigate how the index profile of a few-mode fiber (FMF) can be designed so
that group velocities of the two lowest-order modes can be equalized at a
normalized frequency, which is below the cut-off frequency of the LP21
mode. This can be achieved using a single-clad power-law profile with a
sufficiently large profile exponent or a double-clad profile consisting of a
graded-core surrounded by a sufficiently thick depressed inner cladding without
index jump at their interface. The fabrication tolerances, effective index
differences, intramodal dispersion differences, and effective mode areas of
various single- and double-clad profiles are compared. The results show that, in
comparison to single-clad fibers, double-clad fibers are capable of producing
higher fabrication tolerances and reduced sensitivity of group delay difference
to wavelength by three and two orders of magnitude, respectively. Our analyses
provide insights into the design of FMFs, which will facilitate future
development of high-capacity mode division long-haul transmission systems.
PMID- 25121433
TI - Dynamical deformed Airy beams with arbitrary angles between two wings.
AB - We study both numerically and experimentally the acceleration and propagation
dynamics of 2D Airy beams with arbitrary initial angles between their "two
wings." Our results show that the acceleration of these generalized 2D Airy beams
strongly depends on the initial angles and cannot be simply described by the
vector superposition principle (except for the normal case of a 90 degrees
angle). However, as a result of the "Hyperbolic umbilic" catastrophe (a two-layer
caustic), the main lobes of these 2D Airy beams still propagate along parabolic
trajectories even though they become highly deformed. Under such conditions, the
peak intensity (leading energy flow) of the 2D Airy beams cannot be confined
along the main lobe, in contrast to the normal 90 degrees case. Instead, it is
found that there are two parabolic trajectories describing the beam propagation:
one for the main lobe, and the other for the peak intensity. Both trajectories
can be readily controlled by varying the initial wing angle. Due to their self
healing property, these beams tend to evolve into the well-known 1D or 2D Airy
patterns after a certain propagation distance. The theoretical analysis
corroborates our experimental observations, and explains clearly why the
acceleration of deformed Airy beams increases with the opening of the initial
wing angle.
PMID- 25121434
TI - Analysis of Fibonacci gratings and their diffraction patterns.
AB - Aperiodic and fractal optical elements are proving to be promising candidates in
image-forming devices. In this paper, we analyze the diffraction patterns of
Fibonacci gratings (FbGs), which are prototypical examples of aperiodicity. They
exhibit novel characteristics such as redundancy and robustness that keep their
imaging characteristics intact even when there is significant loss of
information. FbGs also contain fractal signatures and are characterized by a
fractal dimension. Our study suggests that aperiodic gratings may be better than
their fractal counterparts in technologies based on such architectures. We also
identify the demarcating features of aperiodic and fractal diffraction, which
have been rather fuzzy in the literature so far.
PMID- 25121435
TI - Changing correlation into anticorrelation by superposing thermal and laser light.
AB - Correlation can be changed into anticorrelation by superposing thermal and laser
light with the same frequency and polarization. Two-photon interference theory is
employed to interpret this phenomenon. An experimental scheme is designed to
verify the theoretical predictions by employing pseudothermal light to simulate
thermal light. The experimental results are consistent with the theoretical
results.
PMID- 25121436
TI - Temporal dark adaptation to spatially complex backgrounds: effect of an
additional light source.
AB - Visual adaptation (and especially dark adaptation) has been studied extensively
in the past, however, mainly addressing adaptation to fully dark backgrounds. At
this stage, it is unclear whether these results are not too simple to be applied
to complex situations, such as predicting adaptation of a motorist driving at
night. To fill this gap we set up a study investigating how spatially complex
backgrounds influence temporal dark adaptation. Our results showed that dark
adaptation to spatially complex backgrounds leads to much longer adaptation times
than dark adaptation to spatially uniform backgrounds. We conclude therefore that
the adaptation models based on past studies overestimate the visual system's
sensitivity to detect luminance variations in spatially complex environments. Our
results also showed large variations in adaptation times when varying the degree
of spatial complexity of the background. Hence, we may conclude that it is
important to take into account models that are based on spatially complex
backgrounds when predicting dark adaptation for complex environments.
PMID- 25121437
TI - Rayleigh approximation for the scattering of small partially charged sand
particles.
AB - Based on the Rayleigh approximation, this paper presents the electromagnetic
scattering properties of the small partially charged isotropic sphere and those
of a similar anisotropic sphere and then discusses the effect of surface charges
on particles' optical properties. The numerical simulation results show that the
surface charges on a charged particle can enhance the scattering of the incident
waves, and the effect on an anisotropic charged sphere is much greater than that
on an isotropic charged particle. Therefore it is necessary to consider the
medium property (isotropic or anisotropic) and electric effects of dust particles
in the remote sensing of sandstorms.
PMID- 25121439
TI - Custom-modified three-dimensional periodic microstructures by pattern-integrated
interference lithography.
AB - By combining interference lithography and projection photolithography
concurrently, pattern-integrated interference lithography (PIIL) enables the
wafer-scale, rapid, and single-exposure fabrication of multidimensional periodic
microstructures that integrate arbitrary functional elements. To date, two
dimensional PIIL has been simulated and experimentally demonstrated. In this
paper, we report new simulated results of PIIL exposures for various custom
modified three-dimensional (3D) periodic structures. These results were generated
using custom PIIL comprehensive vector modeling. Simulations include mask
integrated and mask-shaped 3D periodic arrangements as well as microcavities on
top of or fully embedded within 3D periodic structures. These results indicate
PIIL is a viable method for making versatile 3D periodic microstructures.
PMID- 25121438
TI - Corresponding color datasets and a chromatic adaptation model based on the OSA
UCS system.
AB - Today chromatic adaptation transforms (CATs) are reconsidered, since their
mathematical inconsistency has been shown in Color Res. Appl.38, 188 (2013) and
by the CIE technical committee TC 8-11: CIECAM02 Mathematics. In 2004-2005 the
author proposed an adaptation transform based on the uniform color scale system
of the Optical Society of America (OSA-UCS) [J. Opt. Soc. Am. A21, 677 (2004);
Color Res. Appl. 30, 31 (2005)] that transforms the cone-activation stimuli into
adapted stimuli. The present work considers all the 37 available corresponding
color (CC) datasets selected by CIE and (1) shows that the adapted stimuli
obtained from CC data are defined up to an unknown transformation, and an
unambiguous definition of the adapted stimuli requires additional hypotheses or
suitable experimental data (as it is in the OSA-UCS system); (2) produces a CAT,
represented by a linear transformation between CCs, associated with any CC
dataset, whose high quality measured in DeltaE units discards the possibility of
nonlinear transformations; (3) analyzes these color-conversion matrices in a
heuristic way with a reference adaptation that is approximately that of the OSA
UCS adapted colors for the D65 illuminant and particularly shows accordance with
the Hunt effect and the Bezold-Brucke hue shift; (4) proposes the measurements of
CC stimuli with a reference adaptation equal to that of the visual situation of
the OSA-UCS system for defining adapted colors for any considered illumination
adaptation and therefore for defining a general CAT formula.
PMID- 25121440
TI - Rapid computation of the amplitude and phase of tightly focused optical fields
distorted by scattering particles.
AB - We develop an efficient method for accurately calculating the electric field of
tightly focused laser beams in the presence of specific configurations of
microscopic scatterers. This Huygens-Fresnel wave-based electric field
superposition (HF-WEFS) method computes the amplitude and phase of the scattered
electric field in excellent agreement with finite difference time-domain (FDTD)
solutions of Maxwell's equations. Our HF-WEFS implementation is 2-4 orders of
magnitude faster than the FDTD method and enables systematic investigations of
the effects of scatterer size and configuration on the focal field. We
demonstrate the power of the new HF-WEFS approach by mapping several metrics of
focal field distortion as a function of scatterer position. This analysis shows
that the maximum focal field distortion occurs for single scatterers placed below
the focal plane with an offset from the optical axis. The HF-WEFS method
represents an important first step toward the development of a computational
model of laser-scanning microscopy of thick cellular/tissue specimens.
PMID- 25121441
TI - Unitary rotations in two-, three-, and D-dimensional Cartesian data arrays.
AB - Using a previous technique to rotate two-dimensional images on an N*N square
pixellated screen unitarily, we can rotate three-dimensional pixellated cubes of
side N, and also generally D-dimensional Cartesian data arrays, also unitarily.
Although the number of operations inevitably grows as N(2D) (because each rotated
pixel depends on all others), and Gibbs-like oscillations are inevitable, the
result is a strictly unitary and real transformation (thus orthogonal) that is
invertible (thus no loss of information) and could be used as a standard.
PMID- 25121443
TI - Pattern recognition based on the correlated intensity fluctuations of thermal
light.
AB - Here we present a pattern recognition scheme based on the intensity correlation
of thermal light. We prove theoretically that under spatially incoherent
illumination the matched filtering technique can be realized in the ghost imaging
field. Using the matched filtering technique, it is possible to distinguish an
object from a preestablished set of objects through their ghost images, which are
extracted by means of intensity correlation measurement. According to the pattern
recognition scheme, we present a numerical simulation in which we can easily
identify the character inserted into the object arm from a set of two characters
through the position of the autocorrelation peak. This pattern recognition scheme
opens up the possibility of performing coherent optical processing under
spatially incoherent illumination.
PMID- 25121442
TI - Signal-to-noise ratio limitations for intensity correlation imaging.
AB - Intensity correlation imaging (ICI) is a concept which has been considered for
the task of providing images of satellites in geosynchronous orbit using ground
based equipment. This concept is based on the intensity interferometer principle
first developed by Hanbury Brown and Twiss. It is the objective of this paper to
establish that a sun-lit geosynchronous satellite is too faint a target object to
allow intensity interferometry to be used in developing image information about
it-at least not in a reasonable time and with a reasonable amount of equipment.
An analytic treatment of the basic phenomena is presented. This is an analysis of
one aspect of the statistics of the very high frequency random variations of a
very narrow portion of the optical spectra of the incoherent (black-body like
actually reflected sunlight) radiation from the satellite, an analysis showing
that the covariance of this radiation as measured by a pair of ground-based
telescopes is directly proportional to the square of the magnitude of one
component of the Fourier transform of the image of the satellite-the component
being the one for a spatial frequency whose value is determined by the separation
of the two telescopes. This analysis establishes the magnitude of the covariance.
A second portion of the analysis considers shot-noise effects. It is shown that
even with much less than one photodetection event (pde) per signal integration
time an unbiased estimate of the covariance of the optical field's random
variations can be developed. Also, a result is developed for the standard
deviation to be associated with the estimated value of the covariance. From these
results an expression is developed for what may be called the signal-to-noise
ratio to be associated with an estimate of the covariance. This signal-to-noise
ratio, it turns out, does not depend on the measurement's integration time,
Deltat (in seconds), or on the optical spectral bandwidth, Deltanu (in Hertz),
utilized-so long as DeltatDeltanu?1, which condition it would be hard to violate.
It is estimated that for a D=3.16 m diameter satellite, with a pair of D=1.0 m
diameter telescopes (which value of D probably represents an upper limit on
allowable aperture diameter since the telescope aperture must be much too small
to even resolve the size of the satellite) at least N=2.55*10(16) separate pairs
of (one integration time, pde count) measurement values must be collected to
achieve just a 10 dB signal-to-noise ratio. Working with 10 pairs of telescopes
(all with the same separation), and with 10 nearly adjacent and each very narrow
spectral bands extracted from the light collected by each of the telescope-so
that for each measurement integration time there would be 100 pairs of
measurement values available-and with an integration time as short as Deltat=1
ns, it would take T=2.55*10(5) s or about 71 h to collect the data for just a
single spatial frequency component of the image of the satellite. It is on this
basis that it is concluded that the ICI concept does not seem likely to be able
to provide a timely responsive capability for the imaging of geosynchronous
satellites.
PMID- 25121444
TI - Scintillations of optical plane and spherical waves in underwater turbulence.
AB - The scintillation indices of optical plane and spherical waves propagating in
underwater turbulent media are evaluated by using the Rytov method, and the
variations in the scintillation indices are investigated when the rate of
dissipation of mean squared temperature, the temperature and salinity
fluctuations, the propagation distance, the wavelength, the Kolmogorov microscale
length, and the rate of dissipation of the turbulent kinetic energy are varied.
Results show that as in the atmosphere, also in underwater media the plane wave
is more affected by turbulence as compared to the spherical wave. The underwater
turbulence effect becomes significant at 5-10 m for a plane wave and at 20-25 m
for a spherical wave. The turbulence effect is relatively small in deep water and
is large at the surface of the water. Salinity-induced turbulence strongly
dominates the scintillations compared to temperature-induced turbulence.
PMID- 25121445
TI - Angular and polarization response of multimode sensors with resistive-grid
absorbers.
AB - High-sensitivity receiver systems with near-ideal polarization sensitivity are
highly desirable for development of millimeter and submillimeter radio astronomy.
Multimoded bolometers provide a unique solution to achieve such sensitivity, for
which hundreds of single-mode sensors would otherwise be required. The primary
concern in employing such multimoded sensors for polarimetery is the control of
the polarization systematics. In this work, we examine the angular- and
polarization-dependent absorption pattern of a thin resistive grid or membrane,
which models an absorber used for a multimoded bolometer. The result shows that a
freestanding thin resistive absorber with a surface resistivity of eta/2, where
eta is the impedance of free space, attains a beam pattern with equal E- and H
plane responses, leading to zero cross-polarization. For a resistive-grid
absorber, the condition is met when a pair of grids is positioned orthogonal to
each other and both have a resistivity of eta/2. When a reflective backshort
termination is employed to improve absorption efficiency, the cross-polar level
can be suppressed below -30 dB if acceptance angle of the sensor is limited to
?60 degrees . The small cross-polar systematics have even-parity patterns and do
not contaminate the measurements of odd-parity polarization patterns, for which
many of the recent instruments for cosmic microwave background are designed.
Underlying symmetry that suppresses these cross-polar systematics is discussed in
detail. The estimates and formalism provided in this work offer key tools in the
design consideration of the instruments using the multimoded polarimeters.
PMID- 25121446
TI - On calculating metamer sets for spectrally tunable LED illuminators.
AB - Solid state lighting is becoming a popular light source for color vision
experiments. One of the advantages of light emitting diodes (LEDs) is the
possibility to shape the target light spectrum according to the experimenter's
needs. In this paper, we present a method for creating metameric lights with an
LED-based spectrally tunable illuminator. The equipment we use consists of six
Gamma Scientific RS-5B lamps, each containing nine different LEDs and a 1 m
integrating sphere. We provide a method for describing the (almost) entire set of
illuminant metamers. It will be shown that the main difficulty in describing this
set arises as the result of the intensity dependent peak-wavelength shift, which
is manifested by the majority of the LEDs used by the illuminators of this type.
We define the normalized metamer set describing all illuminator spectra that
colorimetrically match a given chromaticity. Finally, we describe a method for
choosing the smoothest or least smooth metamer from the entire set.
PMID- 25121447
TI - Bloch modes at the surface of a photonic crystal interacting with a waveguide.
AB - We theoretically studied the influence of an infinite set of waveguides on the
evanescent field of Bloch waves at the surface of a one-dimensional photonic
crystal (PC) excited by a TE Gaussian beam undergoing total internal reflection.
The set of waveguides is regarded as a periodic inhomogeneous medium with period
a. Numerical results are presented for the case in which a is greater than
lambda, which is the wavelength used to excite the surface mode. When the
waveguide tip is very close to the surface of the PC, a fraction of the surface
wave is reflected by the tip, producing an interference pattern that can be
observed in the near field. In this case, the system simulates scanning tunneling
optical microscopy in 2D geometry, and an image of the field distribution of the
surface mode is obtained by quantifying the flux energy throughout the waveguide.
PMID- 25121448
TI - Maxwell-Gaussian beams with cylindrical polarization.
AB - It is common practice to work in the approximation that beam-like radiation
fields are polarized transverse to the propagation axis. However, even in the
paraxial approximation, this fails to correctly describe beam polarization and
propagation characteristics. We present here the paraxial Maxwell's equations for
beams having cylindrical polarization, which describe the full vector structure
of these beams in the paraxial regime. The effect that these relations have on
the polarization and propagation of cylindrically polarized Laguerre-Gauss and
Bessel-Gauss beams is subsequently explored.
PMID- 25121450
TI - One-dimensional finite-elements method for the analysis of whispering gallery
microresonators.
AB - By taking advantage of axial symmetry of the planar whispering gallery
microresonators, the three-dimensional (3D) problem of the resonator is reduced
to a two-dimensional (2D) one; thus, only the cross section of the resonator
needs to be analyzed. Then, the proposed formulation, which works based on a
combination of the finite-elements method (FEM) and Fourier expansion of the
fields, can be applied to the 2D problem. First, the axial field variation is
expressed in terms of a Fourier series. Then, a FEM method is applied to the
radial field variation. This formulation yields an eigenvalue problem with sparse
matrices and can be solved using a well-known numerical technique. This method
takes into account both the radiation loss and the dielectric loss; hence, it
works efficiently either for high number or low number modes. Efficiency of the
method was investigated by comparison of the results with those of commercial
software.
PMID- 25121449
TI - Zernike expansion of derivatives and Laplacians of the Zernike circle
polynomials.
AB - The partial derivatives and Laplacians of the Zernike circle polynomials occur in
various places in the literature on computational optics. In a number of cases,
the expansion of these derivatives and Laplacians in the circle polynomials are
required. For the first-order partial derivatives, analytic results are scattered
in the literature. Results start as early as 1942 in Nijboer's thesis and
continue until present day, with some emphasis on recursive computation schemes.
A brief historic account of these results is given in the present paper. By
choosing the unnormalized version of the circle polynomials, with exponential
rather than trigonometric azimuthal dependence, and by a proper combination of
the two partial derivatives, a concise form of the expressions emerges. This form
is appropriate for the formulation and solution of a model wavefront sensing
problem of reconstructing a wavefront on the level of its expansion coefficients
from (measurements of the expansion coefficients of) the partial derivatives. It
turns out that the least-squares estimation problem arising here decouples per
azimuthal order m, and per m the generalized inverse solution assumes a concise
analytic form so that singular value decompositions are avoided. The preferred
version of the circle polynomials, with proper combination of the partial
derivatives, also leads to a concise analytic result for the Zernike expansion of
the Laplacian of the circle polynomials. From these expansions, the properties of
the Laplacian as a mapping from the space of circle polynomials of maximal degree
N, as required in the study of the Neumann problem associated with the transport
of-intensity equation, can be read off within a single glance. Furthermore, the
inverse of the Laplacian on this space is shown to have a concise analytic form.
PMID- 25121451
TI - Majorization and measures of classical polarization in three dimensions.
AB - There has been much discussion in the literature about rival measures of
classical polarization in three dimensions. We gather and compare the various
proposed measures of polarization, creating a geometric representation of the
polarization state space in the process. We use majorization, previously used in
quantum information, as a criterion to establish a partial ordering on the
polarization state space. Using this criterion and other considerations, the most
useful polarization measure in three dimensions is found to be one dependent on
the Bloch vector decomposition of the polarization matrix.
PMID- 25121452
TI - Partial polarization of optical beams and near fields probed with a
nanoscatterer.
AB - We consider theoretically the detection of the spectral polarization
characteristics of random, partially polarized optical beams and near fields by
probing them with a dipolar nanoparticle. We show that measuring the polarization
state of the scattered far field with a conventional waveplate-polarizer setup,
possibly in several directions, results in the full 3*3 polarization matrix at
the probe site. This allows us to deduce the distributions of the degree of
polarization of the field and the Stokes parameters of the polarized part of the
field with a resolution limited by the probe size. Regarding random near fields
we show that, in analogy with a known result on beam fields, a degree of
polarization of three-component light fields put forward in recent literature can
in some cases be interpreted as a ratio of the intensity in the polarized part of
the light to that of the total field. We demonstrate the technique by considering
the probing of a Gaussian-Schell model beam and a thermally excited near field.
The method extends the current scanning-probe techniques to the detection of
partial polarization of random light fields and can find applications in
nanophotonics and polarization optics.
PMID- 25121453
TI - Silhouette estimation.
AB - Silhouettes arise in a variety of imaging scenarios. Pristine silhouettes are
often degraded via blurring, detector sampling, and detector noise. We present a
maximum a posteriori estimator for the restoration of parameterized facial
silhouettes. Extreme dealiasing and dramatic superresolution, well beyond the
diffraction limit, are demonstrated through the use of strong prior knowledge.
PMID- 25121454
TI - Accuracy of sun localization in the second step of sky-polarimetric Viking
navigation for north determination: a planetarium experiment.
AB - It is a widely discussed hypothesis that Viking seafarers might have been able to
locate the position of the occluded sun by means of dichroic or birefringent
crystals, the mysterious sunstones, with which they could analyze skylight
polarization. Although the atmospheric optical prerequisites and certain aspects
of the efficiency of this sky-polarimetric Viking navigation have been
investigated, the accuracy of the main steps of this method has not been
quantitatively examined. To fill in this gap, we present here the results of a
planetarium experiment in which we measured the azimuth and elevation errors of
localization of the invisible sun. In the planetarium sun localization was
performed in two selected celestial points on the basis of the alignments of two
small sections of two celestial great circles passing through the sun. In the
second step of sky-polarimetric Viking navigation the navigator needed to
determine the intersection of two such celestial circles. We found that the
position of the sun (solar elevation theta(S), solar azimuth phi(S)) was
estimated with an average error of +0.6 degrees <=Deltatheta<=+8.8 degrees and
3.9 degrees <=Deltaphi<=+2.0 degrees . We also calculated the compass direction
error when the estimated sun position is used for orienting with a Viking sun
compass. The northern direction (omega(North)) was determined with an error of
3.34 degrees <=Deltaomega(North)<=+6.29 degrees . The inaccuracy of the second
step of this navigation method was high (Deltaomega(North)=-16.3 degrees ) when
the solar elevation was 5 degrees <=theta(S)<=25 degrees , and the two selected
celestial points were far from the sun (at angular distances 95 degrees
<=gamma(1), gamma(2)<=115 degrees ) and each other (125 degrees <=delta<=145
degrees ). Considering only this second step, the sky-polarimetric navigation
could be more accurate in the mid-summer period (June and July), when in the
daytime the sun is high above the horizon for long periods. In the spring (and
autumn) equinoctial period, alternative methods (using a twilight board, for
example) might be more appropriate. Since Viking navigators surely also committed
further errors in the first and third steps, the orientation errors presented
here underestimate the net error of the whole sky-polarimetric navigation.
PMID- 25121455
TI - Nonparaxial propagation and focusing properties of azimuthal-variant vector
fields diffracted by an annular aperture.
AB - Based on the vectorial Rayleigh-Sommerfeld integrals, the analytical expressions
for azimuthal-variant vector fields diffracted by an annular aperture are
presented. This helps us to investigate the propagation behaviors and the
focusing properties of apertured azimuthal-variant vector fields under
nonparaxial and paraxial approximations. The diffraction by a circular aperture,
a circular disk, or propagation in free space can be treated as special cases of
this general result. Simulation results show that the transverse intensity,
longitudinal intensity, and far-field divergence angle of nonparaxially apertured
azimuthal-variant vector fields depend strongly on the azimuthal index, the outer
truncation parameter and the inner truncation parameter of the annular aperture,
as well as the ratio of the waist width to the wavelength. Moreover, the multiple
ring-structured intensity pattern of the focused azimuthal-variant vector field,
which originates from the diffraction effect caused by an annular aperture, is
experimentally demonstrated.
PMID- 25121456
TI - Spatial-temporal-covariance-based modeling, analysis, and simulation of aero
optics wavefront aberrations.
AB - We introduce a framework for modeling, analysis, and simulation of aero-optics
wavefront aberrations that is based on spatial-temporal covariance matrices
extracted from wavefront sensor measurements. Within this framework, we present a
quasi-homogeneous structure function to analyze nonhomogeneous, mildly
anisotropic spatial random processes, and we use this structure function to show
that phase aberrations arising in aero-optics are, for an important range of
operating parameters, locally Kolmogorov. This strongly suggests that the d5/3
power law for adaptive optics (AO) deformable mirror fitting error, where d
denotes actuator separation, holds for certain important aero-optics scenarios.
This framework also allows us to compute bounds on AO servo lag error and
predictive control error. In addition, it provides us with the means to
accurately simulate AO systems for the mitigation of aero-effects, and it may
provide insight into underlying physical processes associated with turbulent
flow. The techniques introduced here are demonstrated using data obtained from
the Airborne Aero-Optics Laboratory.
PMID- 25121457
TI - Object-color-signal prediction using wraparound Gaussian metamers.
AB - Alexander Logvinenko introduced an object-color atlas based on idealized
reflectances called rectangular metamers in 2009. For a given color signal, the
atlas specifies a unique reflectance that is metameric to it under the given
illuminant. The atlas is complete and illuminant invariant, but not possible to
implement in practice. He later introduced a parametric representation of the
object-color atlas based on smoother "wraparound Gaussian" functions. In this
paper, these wraparound Gaussians are used in predicting illuminant-induced color
signal changes. The method proposed in this paper is based on computationally
"relighting" that reflectance to determine what its color signal would be under
any other illuminant. Since that reflectance is in the metamer set the prediction
is also physically realizable, which cannot be guaranteed for predictions
obtained via von Kries scaling. Testing on Munsell spectra and a multispectral
image shows that the proposed method outperforms the predictions of both those
based on von Kries scaling and those based on the Bradford transform.
PMID- 25121458
TI - Modulation transfer function of a triangular pixel array detector.
AB - The modulation transfer function (MTF) is the main parameter that is used to
evaluate image quality in electro-optical systems. Detector sampling MTF in most
electro-optical systems determines the cutoff frequency of the system. The MTF of
the detector depends on its pixel shape. In this work, we calculated the MTF of a
detector with an equilateral triangular pixel shape. Some new results were found
in deriving the MTF for the equilateral triangular pixel shape.
PMID- 25121459
TI - Validity of the Dysexecutive Questionnaire (DEX). Ratings by patients with brain
injury and their therapists.
AB - OBJECTIVE: This study investigated the validity of the DEX-Questionnaire (both
completed by patients, DEX-Self and by therapists, DEX-TH), included in the
Behavioural Assessment of the Dysexecutive Syndrome (BADS), at identifying
differences in the severity of dysexecutive symptoms according to lesion
location. It also examined the strength of associations of the DEX-Self and the
DEX-TH reports with the sub-tests of the BADS as well as two other real-life
executive tasks, the Everyday Description Task and the Twenty Question Test.
METHODS: This study compared 30 patients with anterior lesions (AL) to 22
patients with posterior lesions (PL). Twenty-nine healthy participants and their
relatives were included as controls. RESULTS: Significant group differences were
found only on the DEX-TH, but not on the DEX-Self, indicating poor insight in
patients with AL. The DEX-TH were revealed accurate in detecting more severe
dysexecutive symptoms in the AL group. Furthermore, only the DEX-TH reportings
were significantly correlated with the above executive tests. Multiple regression
analysis showed that the Modified Six Elements Test, a sub-test of the BADS,
predicted DEX-TH as accurately as the total BADS. CONCLUSION: The DEX-TH
reportings and the MSET can provide valuable information about the severity of
daily executive dysfunctioning, with implications for cognitive rehabilitation.
PMID- 25121460
TI - Mixtures of lecithin and bile salt can form highly viscous wormlike micellar
solutions in water.
AB - The self-assembly of biological surfactants in water is an important topic for
study because of its relevance to physiological processes. Two common types of
biosurfactants are lecithin (phosphatidylcholine) and bile salts, which are both
present in bile and involved in digestion. Previous studies on lecithin-bile salt
mixtures have reported the formation of short, rodlike micelles. Here, we show
that lecithin-bile salt micelles can be further induced to grow into long,
flexible wormlike structures. The formation of long worms and their resultant
entanglement into transient networks is reflected in the rheology: the fluids
become viscoelastic and exhibit Maxwellian behavior, and their zero-shear
viscosity can be up to a 1000-fold higher than that of water. The presence of
worms is further confirmed by data from small-angle neutron and X-ray scattering
and from cryo-transmission electron microscopy (cryo-TEM). We find that micellar
growth peaks at a specific molar ratio (near equimolar) of bile salt:lecithin,
which suggests a strong binding interaction between the two species. In addition,
micellar growth also requires a sufficient concentration of background
electrolyte such as NaCl or sodium citrate that serves to screen the
electrostatic repulsion of the amphiphiles and to "salt out" the amphiphiles. We
postulate a mechanism based on changes in the molecular geometry caused by bile
salts and electrolytes to explain the micellar growth.
PMID- 25121461
TI - Isotopic fractionation by a fungal P450 nitric oxide reductase during the
production of N2O.
AB - Nitrous oxide (N2O) is a potent greenhouse gas with a 100-year global warming
potential approximately 300 times that of CO2. Because microbes account for over
75% of the N2O released in the U.S., understanding the biochemical processes by
which N2O is produced is critical to our efforts to mitigate climate change. In
the current study, we used gas chromatography-isotope ratio mass spectrometry (GC
IRMS) to measure the delta(15)N, delta(18)O, delta(15)N(alpha), and
delta(15)N(beta) of N2O generated by purified fungal nitric oxide reductase
(P450nor) from Histoplasma capsulatum. The isotope values were used to calculate
site preference (SP) values (difference in delta(15)N between the central (alpha)
and terminal (beta) N atoms in N2O), enrichment factors (epsilon), and kinetic
isotope effects (KIEs). Both oxygen and N(alpha) displayed normal isotope effects
during enzymatic NO reduction with epsilon values of -25.70/00 (KIE = 1.0264) and
-12.60/00 (KIE = 1.0127), respectively. However, bulk nitrogen (average
delta(15)N of N(alpha) and N(beta)) and N(beta) exhibited inverse isotope effects
with epsilon values of 14.00/00 (KIE = 0.9862) and 36.10/00 (KIE = 0.9651),
respectively. The observed inverse isotope effect in delta(15)N(beta) is
consistent with reversible binding of the first NO in the P450nor reaction
mechanism. In contrast to the constant SP observed during NO reduction in
microbial cultures, the site preference measured for purified H. capsulatum
P450nor was not constant, increasing from ~ 150/00 to ~ 290/00 during the course
of the reaction. This indicates that SP for microbial cultures can vary depending
on the growth conditions, which may complicate source tracing during microbial
denitrification.
PMID- 25121462
TI - Vitamin D deficiency and infertility: insights from in vitro fertilization
cycles.
AB - CONTEXT: Vitamin D deficiency has been proven to affect fertility in mammals, but
data in human is less convincing. In particular, data on in vitro fertilization
(IVF), an attractive model to draw information on this topic, are sparse and
conflicting. OBJECTIVE: Our objective was to investigate IVF outcome in women
with deficient 25-hydroxy-vitamin D [25(OH)D] serum levels (<20 ng/mL). DESIGN
AND SETTING: This prospective cross-sectional study was conducted at the
infertility unit of an academic setting. PATIENTS: The main inclusion criteria
were as follows: (1) indication to IVF, (2) age 18-42 years, (3) BMI 18-25
kg/m(2), (4) adequate ovarian reserve according to Bologna criteria. Eligible
women provided a serum sample for 25(OH)D measurement at the time of cycle
preparation. Subjects were subsequently excluded if the cycle was cancelled or if
the attempt was excessively delayed. INTERVENTION: Quantitative detection of
serum 25(OH)D. MAIN OUTCOME MEASURE: Clinical pregnancy rate. RESULTS: The number
of recruited women with serum 25(OH)D <20 ng/mL and >= 20 ng/mL was 154 and 181,
respectively. The clinical pregnancy rates were 20% (30/154) and 31% (56/181),
respectively (P = .02); the adjusted odds ratio for clinical pregnancy in women
with vitamin D >= 20 ng/mL was 2.15 (95% CI: 1.23-3.77). Subgroup analyses showed
that the group of women with the highest serum levels (>30 ng/mL) had the highest
chances of pregnancy. CONCLUSIONS: Vitamin D is an emerging factor influencing
female fertility and IVF outcome. Additional studies are pressingly needed to
confirm a causal relationship and to investigate the potential therapeutic
benefits of vitamin D supplementation.
PMID- 25121463
TI - 131I-noriodocholesterol uptake by testicular adrenal rest tumors in a patient
with classical 21-hydroxylase deficiency.
PMID- 25121465
TI - Copper clusters as novel fluorescent probes for the detection and photocatalytic
elimination of lead ions.
AB - A new homogeneous assay for a fast, selective and sensitive detection and
elimination of lead ions has been developed using copper clusters as novel
fluorescent probes in aqueous solutions. At the same time, their elimination is
achieved using the efficient photocatalytic activity of such clusters. Both
effects are explained in terms of an efficient electron transfer due to the LUMO
energy of the cluster overlapping with the ion redox potential. The mechanism,
which allows the explanation of previously reported results for different types
of metal clusters, is further confirmed using smaller and larger Cu clusters
displaying non-selective and non-quenching luminescence in the presence of
different cations.
PMID- 25121471
TI - It's a small World.
PMID- 25121464
TI - Urinary phthalate metabolites are associated with decreased serum testosterone in
men, women, and children from NHANES 2011-2012.
AB - CONTEXT: There is evidence of declining trends in T levels among men in recent
decades, as well as trends in related conditions at multiple life stages and in
both sexes. There is also animal and limited human evidence that exposure to
phthalates, chemicals found in plastics and personal care products, is associated
with reduced androgen levels and associated disorders. OBJECTIVE: To explore
relationships between urinary concentrations of 13 phthalate metabolites and
serum total T levels among men, women, and children when adjusting for important
confounders and stratifying by sex and age (6-12, 12-20, 20-40, 40-60, and 60-80
y). DESIGN: A cross-sectional study. SETTING: US National Health and Nutrition
Examination Survey, 2011-2012. PATIENTS OR OTHER PARTICIPANTS: US general
population. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Serum total T measured by
isotope dilution-liquid chromatography-tandem mass spectrometry. RESULTS:
Multiple phthalates were associated with significantly reduced T in both sexes
and in differing age groups. In females, the strongest and most consistent
inverse relationships were found among women ages 40-60 years. In boys 6-12 years
old, an interquartile range increase in metabolites of di-2-ethylhexyl phthalate
was associated with a 29% (95% confidence interval, 6, 47) reduction in T. In
adult men, the only significant or suggestive inverse associations between
phthalates (metabolites of di-2-ethylhexyl phthalate and dibutyl phthalate) and T
were observed among men ages 40-60 years. CONCLUSIONS: Because T plays an
important role in all life stages for both sexes, future efforts should focus on
better defining these relationships and their broader impacts.
PMID- 25121472
TI - Fine structures of self-assembled beta-cyclodextrin/Pluronic in dilute and dense
systems: a small angle X-ray scattering study.
AB - The evolution of the fine structures of self-assembled polypseudorotaxane (PPR)
in Pluronic (PL F108) solutions containing dilute to dense beta-cyclodextrin
(beta-CD) was illustrated for the first time by small angle X-ray scattering
(SAXS). Dense beta-CD (~19 w/v%) was found feasible to be dispersed in 24% citric
acid solution. 5% of PL F108 formed cylindrical micelles of 1 nm in radius and 8
nm in length in the presence of 24% citric acid through the dehydration of citric
acid and citrate. PPR was formed through host-guest interaction between PL F108
and beta-CD. In dilute beta-CD system (1%), the single chains of PPR with
separated beta-CD stacks on PL F108 were formed. The numbers of beta-CD in each
stack increased from 1 to 4 on increasing beta-CD concentration to 9%. In a dense
beta-CD system, PPR condensed to correlated structures majorly composed of two
unit blocks through the hydrogen bonds between PPRs. Two distinguishable
correlated domains with correlation lengths of 50 nm (marked alpha-phase) and 46
nm (marked beta-phase) along the chains, but without fine periodic structure
within each individual domain, were identified in the 10% beta-CD solution.
Periodic stacking of beta-CD in the domains developed in the 12% solution. As
beta-CD concentration increased from 12 to 19%, the correlated heights of alpha
and beta phases reduced from 41 and 32 nm to 30 and 10 nm, respectively. There
were 48 beta-CDs that stabilized on each PL F108 chain in the 19% beta-CD system,
which is in good agreement with stoichiometry.
PMID- 25121473
TI - Graft and patient survival outcomes of a third kidney transplant.
AB - BACKGROUND: The waiting time for deceased donor renal transplantation in the
United States continues to grow. Retransplant candidates make up a small but
growing percentage of the overall transplant waiting list and raise questions
about the stewardship of scarce resources. The utility of renal transplantation
among individuals with two prior renal transplants is not described in the
literature, and we thus sought to determine the survival benefit associated with
a third kidney transplant (3KT). METHODS: Multivariable Cox regression models
were created to determine characteristics associated with 3KT outcomes and the
survival benefit of 3KT among recipients wait listed and transplanted within the
United States between 1995 and 2009. RESULTS: A total of 4,334 patients were
waitlisted for a 3KT and 2,492 patients received a 3KT. In a multivariate
analysis, 3KT demonstrated an overall patient survival benefit compared to the
waitlist (hazards ratio, 0.379; 95% confidence interval, 0.302-0.475; P<0.001)
for those awaiting their first, second, or third kidney transplants, although an
inferior graft outcome compared to first kidney transplants. The time to survival
benefit did not accrue until 8 months after transplantation. In addition, we
found that the duration of second graft survival was predictive of third graft
survival, such that second graft survival beyond 5 years is associated with
superior 3KT graft survival. Second graft loss in 30 days or less was not
associated with inferior 3KT graft survival. CONCLUSION: A 3KT achieves a
survival benefit over remaining on the waitlist, although is associated with
inferior graft outcomes compared to first kidney transplants. Graft survival of
the second transplant beyond 5 years is associated with superior 3KT graft
survival.
PMID- 25121475
TI - Eculizumab and splenectomy as salvage therapy for severe antibody-mediated
rejection after HLA-incompatible kidney transplantation.
AB - BACKGROUND: Incompatible live donor kidney transplantation is associated with an
increased rate of antibody-mediated rejection (AMR) and subsequent transplant
glomerulopathy. For patients with severe, oliguric AMR, graft loss is inevitable
without timely intervention. METHODS: We reviewed our experience rescuing kidney
allografts with this severe AMR phenotype by using splenectomy alone (n=14),
eculizumab alone (n=5), or splenectomy plus eculizumab (n=5), in addition to
plasmapheresis. RESULTS: The study population was 267 consecutive patients with
donor-specific antibody undergoing desensitization. In the first 3 weeks after
transplantation (median=6 days), 24 patients developed sudden onset oliguria and
rapidly rising serum creatinine with marked rebound of donor-specific antibody,
and a biopsy that showed features of AMR. At a median follow-up of 533 days, 4 of
14 splenectomy-alone patients experienced graft loss (median=320 days), compared
to four of five eculizumab-alone patients with graft failure (median=95 days). No
patients treated with splenectomy plus eculizumab experienced graft loss. There
was more chronic glomerulopathy in the splenectomy-alone and eculizumab-alone
groups at 1 year, whereas splenectomy plus eculizumab patients had almost no
transplant glomerulopathy. CONCLUSION: These data suggest that for patients
manifesting early severe AMR, splenectomy plus eculizumab may provide an
effective intervention for rescuing and preserving allograft function.
PMID- 25121474
TI - Indicators of treatment responsiveness to rituximab and plasmapheresis in
antibody-mediated rejection after kidney transplantation.
AB - BACKGROUND: Treatment of patients with antibody-mediated rejection (AMR) after
kidney transplantation by rituximab and plasmapheresis is ambiguous. Because of
its unknown efficiency and serious side effects, biomarkers, which are predictive
for responsiveness to this treatment in AMR patients, are required. METHODS:
Twenty renal transplant patients were included in this retrospective study.
Selection was based on Renal Index Biopsies, classified according to Banff within
3 months before treatment. Patients were categorized into responders (R) and
nonresponders (NR) depending on whether they returned to dialysis within 6 months
after initiation of rituximab treatment. Clinical, histopathologic (Banff
classification) and serologic parameters were compared between both groups by t
test, Mann-Whitney U test, or likelihood ratio chi-square test. RESULTS: In
comparisons between the groups, the R group showed a 1.5-fold higher level of
estimated glomerular filtration rate and a fourfold lower level of proteinuria.
By contrast, there were no differences in the histologic scores for chronic
transplant lesions between the groups. The t and i scores were higher in NRs,
whereas Banff-C4d scores of peritubular capillaries were increased in the Rs.
Transplant biopsies in the Rs exhibited more CD138+ cell infiltrates. Serologic
determination of human leukocyte antigen antibodies showed higher positivity for
human leukocyte antigen class II donor-specific antibodies in the R group. No
significant differences in other clinical criteria were found. CONCLUSION:
Increased proteinuria, decreased graft function, and a higher grade of tubulitis
and inflammation in AMR are negative predictors for responsiveness to rituximab
therapy. Rituximab therapy therefore should be initiated in an early phase of
AMR.
PMID- 25121476
TI - Outcomes after pregnancy in living lobar lung transplantation.
AB - Pregnancy after lung transplantation has been described, but pregnancy after
living donor lobar lung transplantation (LDLT) has not been reported. The aim of
this study was to evaluate outcomes after pregnancy with LDLT and discuss current
recommendations regarding pregnancy and lung transplantation. A total of four
LDLT patients and five pregnancies were identified, all from our institution. No
patient has developed worsening pulmonary function or acute or chronic rejection.
The complications of pulmonary hypertension and rejection may be overestimated in
this population, and recommendations for preventive sterilization at
transplantation or abortion at the time of conception are likely unwarranted and
unnecessary.
PMID- 25121477
TI - Contact tracing investigation after professional exposure to tuberculosis in a
Swiss hospital using both tuberculin skin test and IGRA.
AB - SETTING: A 950 bed teaching hospital in Switzerland. AIM: To describe the result
of a contact investigation among health care workers (HCW) and patients after
exposure to a physician with smear-positive pulmonary tuberculosis in a hospital
setting using standard tuberculin skin tests (TST) and Interferon-gamma release
assay (IGRA). METHOD: HCW with a negative or unknown TST at hiring had a TST two
weeks after the last contact with the index case (T0), repeated six weeks later
if negative (T6). All exposed HCW had a T-SPOT.TB at T0 and T6. Exposed patients
had a TST six weeks after the last contact, and a T-SPOT.TB if the TST was
positive. RESULTS: Among 101 HCW, 17/73 (22%) had a positive TST at T0. TST was
repeated in 50 at T6 and converted from negative to positive in eight (16%).
Twelve HCW had a positive T-SPOT.TB at T0 and ten converted from negative to
positive at T6. Seven HCW with a positive T-SPOT.TB reverted to negative at T6 or
at later controls, most of them with test values close to the cut-off. Among 27
exposed patients tested at six weeks, ten had a positive TST, five of them
confirmed by a positive T-SPOT.TB. CONCLUSIONS: HCW tested twice after exposure
to a case of smear-positive pulmonary TB demonstrated a possible conversion in
10% with T-SPOT and 16% with TST. Some T-SPOT.TB reverted from positive to
negative during the follow-up, mostly tests with a value close to the cut-off.
Due to the variability of the test results, it seems advisable to repeat the test
with values close to the cut-off before diagnosing the presence of a tuberculous
infection.
PMID- 25121478
TI - Review of recent developments in stimulated emission depletion microscopy:
applications on cell imaging.
AB - Stimulated emission depletion (STED) microscopy is one type of far-field optical
technique demonstrated to provide subdiffraction resolution. STED microscopy
utilizes a donut-shaped depletion beam to limit the probe volume to be much
smaller than a diffraction-limited spot. Resolutions as small as a few tens of
nanometers laterally are reported for cell analysis. The different versions of
STED microscopes are described and contrasted in terms of their applicability for
biological imaging. Finally, we suggest likely avenues for improving the
performance and increasing the utility of STED microscopy.
PMID- 25121479
TI - Performance assessment of time-domain optical brain imagers, part 1: basic
instrumental performance protocol.
AB - Performance assessment of instruments devised for clinical applications is of key
importance for validation and quality assurance. Two new protocols were developed
and applied to facilitate the design and optimization of instruments for time
domain optical brain imaging within the European project nEUROPt. Here, we
present the "Basic Instrumental Performance" protocol for direct measurement of
relevant characteristics. Two tests are discussed in detail. First, the
responsivity of the detection system is a measure of the overall efficiency to
detect light emerging from tissue. For the related test, dedicated solid slab
phantoms were developed and quantitatively spectrally characterized to provide
sources of known radiance with nearly Lambertian angular characteristics. The
responsivity of four time-domain optical brain imagers was found to be of the
order of 0.1 m2 sr. The relevance of the responsivity measure is demonstrated by
simulations of diffuse reflectance as a function of source-detector separation
and optical properties. Second, the temporal instrument response function (IRF)
is a critically important factor in determining the performance of time-domain
systems. Measurements of the IRF for various instruments were combined with
simulations to illustrate the impact of the width and shape of the IRF on
contrast for a deep absorption change mimicking brain activation.
PMID- 25121481
TI - Polarized Raman spectroscopic investigations on hemoglobin ordering in red blood
cells.
AB - We have investigated the dependence of the Raman spectrum of an optically trapped
red blood cell (RBC) on the orientation of the cell, relative to the polarization
direction of the Raman excitation beam. The Raman scattered light polarized
parallel to the polarization direction of the excitation beam was observed to
depend upon the orientation of the cell. In particular, the heme bands at ~754 cm
1 and in the 1500 to 1700 cm-1 region were observed to become maximum when the
cells' equatorial plane was parallel to the excitation beam polarization
direction and minimum when the cells' plane was normal to the polarization
direction. In contrast, no significant orientational dependence was seen in the
Raman scattered light polarized orthogonal to the polarization direction of the
excitation beam. Theoretical simulations carried out to investigate these
observations suggest that inside the RBCs, the hemoglobin molecules must be
present in an ordered arrangement, such that heme-porphyrin planes become
preferentially orientated parallel to the RBCs' equatorial plane.
PMID- 25121480
TI - Performance assessment of time-domain optical brain imagers, part 2: nEUROPt
protocol.
AB - The nEUROPt protocol is one of two new protocols developed within the European
project nEUROPt to characterize the performances of time-domain systems for
optical imaging of the brain. It was applied in joint measurement campaigns to
compare the various instruments and to assess the impact of technical
improvements. This protocol addresses the characteristic of optical brain imaging
to detect, localize, and quantify absorption changes in the brain. It was
implemented with two types of inhomogeneous liquid phantoms based on Intralipid
and India ink with well-defined optical properties. First, small black inclusions
were used to mimic localized changes of the absorption coefficient. The position
of the inclusions was varied in depth and lateral direction to investigate
contrast and spatial resolution. Second, two-layered liquid phantoms with
variable absorption coefficients were employed to study the quantification of
layer-wide changes and, in particular, to determine depth selectivity, i.e., the
ratio of sensitivities for deep and superficial absorption changes. We introduce
the tests of the nEUROPt protocol and present examples of results obtained with
different instruments and methods of data analysis. This protocol could be a
useful step toward performance tests for future standards in diffuse optical
imaging.
PMID- 25121482
TI - Distinct APC subtypes drive spatially segregated CD4+ and CD8+ T-cell effector
activity during skin infection with HSV-1.
AB - Efficient infection control requires potent T-cell responses at sites of pathogen
replication. However, the regulation of T-cell effector function in situ remains
poorly understood. Here, we show key differences in the regulation of effector
activity between CD4+ and CD8+ T-cells during skin infection with HSV-1. IFN
gamma-producing CD4+ T cells disseminated widely throughout the skin and draining
lymph nodes (LN), clearly exceeding the epithelial distribution of infectious
virus. By contrast, IFN-gamma-producing CD8+ T cells were only found within the
infected epidermal layer of the skin and associated hair follicles.
Mechanistically, while various subsets of lymphoid- and skin-derived dendritic
cells (DC) elicited IFN-gamma production by CD4+ T cells, CD8+ T cells responded
exclusively to infected epidermal cells directly presenting viral antigen.
Notably, uninfected cross-presenting DCs from both skin and LNs failed to trigger
IFN-gamma production by CD8+ T-cells. Thus, we describe a previously
unappreciated complexity in the regulation of CD4+ and CD8+ T-cell effector
activity that is subset-specific, microanatomically distinct and involves largely
non-overlapping types of antigen-presenting cells (APC).
PMID- 25121483
TI - Serotonin 5-HT3 receptor-mediated vomiting occurs via the activation of
Ca2+/CaMKII-dependent ERK1/2 signaling in the least shrew (Cryptotis parva).
AB - Stimulation of 5-HT3 receptors (5-HT3Rs) by 2-methylserotonin (2-Me-5-HT), a
selective 5-HT3 receptor agonist, can induce vomiting. However, downstream
signaling pathways for the induced emesis remain unknown. The 5-HT3R channel has
high permeability to extracellular calcium (Ca(2+)) and upon stimulation allows
increased Ca(2+) influx. We examined the contribution of Ca(2+)/calmodulin
dependent protein kinase IIalpha (Ca(2+)/CaMKIIalpha), interaction of 5-HT3R with
calmodulin, and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling to 2
Me-5-HT-induced emesis in the least shrew. Using fluo-4 AM dye, we found that 2
Me-5-HT augments intracellular Ca(2+) levels in brainstem slices and that the
selective 5-HT3R antagonist palonosetron, can abolish the induced Ca(2+)
signaling. Pre-treatment of shrews with either: i) amlodipine, an antagonist of L
type Ca(2+) channels present on the cell membrane; ii) dantrolene, an inhibitor
of ryanodine receptors (RyRs) Ca2+-release channels located on the endoplasmic
reticulum (ER); iii) a combination of their less-effective doses; or iv)
inhibitors of CaMKII (KN93) and ERK1/2 (PD98059); dose-dependently suppressed
emesis caused by 2-Me-5-HT. Administration of 2-Me-5-HT also significantly: i)
enhanced the interaction of 5-HT3R with calmodulin in the brainstem as revealed
by immunoprecipitation, as well as their colocalization in the area postrema
(brainstem) and small intestine by immunohistochemistry; and ii) activated
CaMKIIalpha in brainstem and in isolated enterochromaffin cells of the small
intestine as shown by Western blot and immunocytochemistry. These effects were
suppressed by palonosetron. 2-Me-5-HT also activated ERK1/2 in brainstem, which
was abrogated by palonosetron, KN93, PD98059, amlodipine, dantrolene, or a
combination of amlodipine plus dantrolene. However, blockade of ER inositol-1, 4,
5-triphosphate receptors by 2-APB, had no significant effect on the discussed
behavioral and biochemical parameters. This study demonstrates that Ca(2+)
mobilization via extracellular Ca(2+) influx through 5-HT3Rs/L-type Ca(2+)
channels, and intracellular Ca(2+) release via RyRs on ER, initiate Ca(2+)
dependent sequential activation of CaMKIIalpha and ERK1/2, which contribute to
the 5-HT3R-mediated, 2-Me-5-HT-evoked emesis.
PMID- 25121485
TI - Compromised dynamic cerebral autoregulation in patients with a right-to-left
shunt: a potential mechanism of migraine and cryptogenic stroke.
AB - BACKGROUND AND PURPOSE: The relationship between right-to-left shunts (RLS) and
migraine and cryptogenic stroke is not well understood. In this study, we
investigated whether RLS are associated with impairment of dynamic cerebral
autoregulation (dCA), which may play a role in migraine and cryptogenic stroke.
METHODS: Sixty-six migraineurs were enrolled in the study, including 36 non-RLS
patients and 30 RLS patients. Non-invasive continuous cerebral blood flow
velocity and arterial blood pressure were recorded simultaneously from each
patient by using transcranial Doppler and servo-controlled plethysmograph,
respectively. Transfer function analysis was applied to derive autoregulatory
parameters of gain, phase difference (PD), and autoregulation index. RESULTS: The
PD in migraineurs with RLS was 50.6 +/- 22.9 degrees, which was significantly
lower than that observed in the non-RLS group (67.2 +/- 18.2 degrees, P<0.001).
The PD in the large RLS group (45.4 +/- 22.6 degrees) was significantly lower
than that of the small RLS group (64.9 +/- 17.1 degrees, P<0.01) and non-RLS
group (P<0.001); however, the PD in the small RLS group was similar to that of
the non-RLS group. The PD in the permanent group (48.8 +/- 19.9 degrees) was
similar to that of the latent group (52.6 +/- 26.1 degrees), and both were
significantly lower than that of the non-RLS group (P<0.05). The autoregulation
index results were similar to the PD findings. CONCLUSIONS: dCA is impaired in
migraineurs with large RLS, and this may represent a potential mechanism linking
RLS, migraine, and cryptogenic stroke.
PMID- 25121484
TI - The protective role of symmetric stem cell division on the accumulation of
heritable damage.
AB - Stem cell divisions are either asymmetric-in which one daughter cell remains a
stem cell and one does not-or symmetric, in which both daughter cells adopt the
same fate, either stem or non-stem. Recent studies show that in many tissues
operating under homeostatic conditions stem cell division patterns are strongly
biased toward the symmetric outcome, raising the question of whether symmetry
confers some benefit. Here, we show that symmetry, via extinction of damaged stem
cell clones, reduces the lifetime risk of accumulating phenotypically silent
heritable damage (mutations or aberrant epigenetic changes) in individual stem
cells. This effect is greatest in rapidly cycling tissues subject to accelerating
rates of damage accumulation over time, a scenario that describes the progression
of many cancers. A decrease in the rate of cellular damage accumulation may be an
important factor favoring symmetric patterns of stem cell division.
PMID- 25121486
TI - Altered resting-state FMRI signals in acute stroke patients with ischemic
penumbra.
AB - BACKGROUND: Identifying the ischemic penumbra in acute stroke subjects is
important for the clinical decision making process. The aim of this study was to
use resting-state functional magnetic resonance singal (fMRI) to investigate the
change in the amplitude of low-frequency fluctuations (ALFF) of these subjects in
three different subsections of acute stroke regions: the infarct core tissue, the
penumbra tissue, and the normal brain tissue. Another aim of this study was to
test the feasilbility of consistently detecting the penumbra region of the brain
through ALFF analysis. METHODS: Sixteen subjects with first-ever acute ischemic
stroke were scanned within 27 hours of the onset of stroke using magnetic
resonance imaging. The core of infarct regions and penumbra regions were
determined by diffusion and perfusion-weighted imaging respectively. The ALFF
were measured from resting-state blood oxygen level dependent (BOLD) fMRI scans.
The averaged relative ALFF value of each regions were correlated with the time
after the onset of stroke. RESULTS: Relative ALFF values were significantly
different in the infarct core tissue, penumbra tissue and normal brain tissue.
The locations of lesions in the ALFF maps did not match perfectly with diffusion
and perfusion-weighted imagings; however, these maps provide a contrast that can
be used to differentiate between penumbra brain tissue and normal brain tissue.
Significant correlations between time after stroke onset and the relative ALFF
values were present in the penumbra tissue but not in the infarct core and normal
brain tissue. CONCLUSION: Preliminary results from this study suggest that the
ALFF reflects the underlying neurovascular activity and has a great potential to
estimate the brain tissue viability after ischemia. Results also show that the
ALFF may contribute to acute stroke imaging for thrombolytic or neuroprotective
therapies.
PMID- 25121487
TI - Agricultural science in the wild: a social network analysis of farmer knowledge
exchange.
AB - Responding to demands for transformed farming practices requires new forms of
knowledge. Given their scale and complexity, agricultural problems can no longer
be solved by linear transfers in which technology developed by specialists passes
to farmers by way of extension intermediaries. Recent research on alternative
approaches has focused on the innovation systems formed by interactions between
heterogeneous actors. Rather than linear transfer, systems theory highlights
network facilitation as a specialized function. This paper contributes to our
understanding of such facilitation by investigating the networks in which farmers
discuss science. We report findings based on the study of a pastoral farming
experiment collaboratively undertaken by a group of 17 farmers and five
scientists. Analysis of prior contact and alter sharing between the group's
members indicates strongly tied and decentralized networks. Farmer knowledge
exchanges about the experiment have been investigated using a mix of quantitative
and qualitative methods. Network surveys identified who the farmers contacted for
knowledge before the study began and who they had talked to about the experiment
by 18 months later. Open-ended interviews collected farmer statements about their
most valuable contacts and these statements have been thematically analysed. The
network analysis shows that farmers talked about the experiment with 192 people,
most of whom were fellow farmers. Farmers with densely tied and occupationally
homogeneous contacts grew their networks more than did farmers with contacts that
are loosely tied and diverse. Thematic analysis reveals three general principles:
farmers value knowledge delivered by persons rather than roles, privilege farming
experience, and develop knowledge with empiricist rather than rationalist
techniques. Taken together, these findings suggest that farmers deliberate about
science in intensive and durable networks that have significant implications for
theorizing agricultural innovation. The paper thus concludes by considering the
findings' significance for current efforts to rethink agricultural extension.
PMID- 25121488
TI - Efficacy and safety of rituximab in children with difficult-to-treat nephrotic
syndrome.
AB - BACKGROUND: Rituximab has emerged as an important medication for patients with
steroid-dependent or steroid-resistant nephrotic syndrome. PATIENTS: We report
the efficacy and safety of therapy with intravenous rituximab, administered once
weekly for 2-4 doses, in 193 patients (mean age 10.9, range 2.2-18.7 years) with
difficult-to-treat steroid dependence (n = 101), calcineurin inhibitor (CNI)
dependent steroid resistance (n = 34) and CNI-resistant nephrotic syndrome (n =
58) managed at this center during 2006-13. OUTCOMES: Therapy in patients with
steroid dependence and CNI-dependent steroid resistance led to significantly
reduced relapse rates (respective mean difference 2.7 relapses/year and 2.2
relapses/year, corresponding to a decrease in relapses by 81.8 and 71.0%; both P
< 0.0001). This resulted in a significant reduction in steroid requirement (mean
difference 104.5 and 113.6 mg/kg/year, respectively; both P < 0.0001) and a trend
to improved standard deviation scores for height (P = 0.069) and body mass index
(P = 0.029). Remission was longer in patients with steroid dependence compared
with CNI-dependent steroid resistance (median 16 versus 10 months; P < 0.0001).
Prior response to cyclophosphamide predicted a lower risk of relapse in the
former (hazard ratio, HR 0.56; P = 0.045); patients with initial resistance and
CNI-dependent steroid resistance had increased risk of relapse (HR 2.66; P =
0.042). B-cell recovery, noted in 62.5% patients at 6 months, was not related to
occurrence of relapse; redosing (n = 42 patients) was safe and effective.
Response to therapy was unsatisfactory in patients with steroid- and CNI
resistant nephrotic syndrome, with remission in 29.3%. Focal segmental
glomerulosclerosis was associated with higher odds of non-response (odds ratio
11.1; P = 0.028) and lack of response was associated with progressive chronic
kidney disease (HR 9.97; P = 0.035). Therapy with rituximab was safe; adverse
effects or infections were noted in 19 (9.8%) patients. CONCLUSIONS: Therapy with
rituximab is effective and safe in reducing relapse rates and need for
immunosuppressive medications in patients with steroid-dependent and CNI
dependent steroid-resistant nephrotic syndrome.
PMID- 25121489
TI - Distribution of schistosomiasis and soil transmitted helminthiasis in Zimbabwe:
towards a national plan of action for control and elimination.
AB - BACKGROUND: Schistosomiasis and STH are among the list of neglected tropical
diseases considered for control by the WHO. Although both diseases are endemic in
Zimbabwe, no nationwide control interventions have been implemented. For this
reason in 2009 the Zimbabwe Ministry of Health and Child Care included the two
diseases in the 2009-2013 National Health Strategy highlighting the importance of
understanding the distribution and burden of the diseases as a prerequisite for
elimination interventions. It is against this background that a national survey
was conducted. METHODOLOGY: A countrywide cross-sectional survey was carried out
in 280 primary schools in 68 districts between September 2010 and August 2011.
Schistosoma haematobium was diagnosed using the urine filtration technique.
Schistosoma mansoni and STH (hookworms, Trichuris trichiura, Ascaris
lumbricoides) were diagnosed using both the Kato Katz and formol ether
concentration techniques. MAIN FINDINGS: Schistosomiasis was more prevalent
country-wide (22.7%) than STH (5.5%). The prevalence of S. haematobium was 18.0%
while that of S. mansoni was 7.2%. Hookworms were the most common STH with a
prevalence of 3.2% followed by A. lumbricoides and T. trichiura with prevalence
of 2.5% and 0.1%, respectively. The prevalence of heavy infection intensity as
defined by WHO for any schistosome species was 5.8% (range 0%-18.3% in
districts). Only light to moderate infection intensities were observed for STH
species. The distribution of schistosomiasis and STH varied significantly between
provinces, districts and schools (p<0.001). Overall, the prevalence of co
infection with schistosomiasis and STH was 1.5%. The actual co-endemicity of
schistosomiasis and STH was observed in 43 (63.2%) of the 68 districts screened.
CONCLUSION AND RECOMMENDATIONS: This study provided comprehensive baseline data
on the distribution of schistosomiasis and STH that formed the basis for
initiating a national control and elimination programme for these two neglected
tropical diseases in Zimbabwe.
PMID- 25121490
TI - Phenotypic robustness and the assortativity signature of human transcription
factor networks.
AB - Many developmental, physiological, and behavioral processes depend on the precise
expression of genes in space and time. Such spatiotemporal gene expression
phenotypes arise from the binding of sequence-specific transcription factors
(TFs) to DNA, and from the regulation of nearby genes that such binding causes.
These nearby genes may themselves encode TFs, giving rise to a transcription
factor network (TFN), wherein nodes represent TFs and directed edges denote
regulatory interactions between TFs. Computational studies have linked several
topological properties of TFNs - such as their degree distribution - with the
robustness of a TFN's gene expression phenotype to genetic and environmental
perturbation. Another important topological property is assortativity, which
measures the tendency of nodes with similar numbers of edges to connect. In
directed networks, assortativity comprises four distinct components that
collectively form an assortativity signature. We know very little about how a
TFN's assortativity signature affects the robustness of its gene expression
phenotype to perturbation. While recent theoretical results suggest that
increasing one specific component of a TFN's assortativity signature leads to
increased phenotypic robustness, the biological context of this finding is
currently limited because the assortativity signatures of real-world TFNs have
not been characterized. It is therefore unclear whether these earlier theoretical
findings are biologically relevant. Moreover, it is not known how the other three
components of the assortativity signature contribute to the phenotypic robustness
of TFNs. Here, we use publicly available DNaseI-seq data to measure the
assortativity signatures of genome-wide TFNs in 41 distinct human cell and tissue
types. We find that all TFNs share a common assortativity signature and that this
signature confers phenotypic robustness to model TFNs. Lastly, we determine the
extent to which each of the four components of the assortativity signature
contributes to this robustness.
PMID- 25121494
TI - Total internal and external ophthalmoplegia as presenting symptoms of Miller
Fisher syndrome.
PMID- 25121492
TI - A simple model of optimal population coding for sensory systems.
AB - A fundamental task of a sensory system is to infer information about the
environment. It has long been suggested that an important goal of the first stage
of this process is to encode the raw sensory signal efficiently by reducing its
redundancy in the neural representation. Some redundancy, however, would be
expected because it can provide robustness to noise inherent in the system.
Encoding the raw sensory signal itself is also problematic, because it contains
distortion and noise. The optimal solution would be constrained further by
limited biological resources. Here, we analyze a simple theoretical model that
incorporates these key aspects of sensory coding, and apply it to conditions in
the retina. The model specifies the optimal way to incorporate redundancy in a
population of noisy neurons, while also optimally compensating for sensory
distortion and noise. Importantly, it allows an arbitrary input-to-output cell
ratio between sensory units (photoreceptors) and encoding units (retinal ganglion
cells), providing predictions of retinal codes at different eccentricities.
Compared to earlier models based on redundancy reduction, the proposed model
conveys more information about the original signal. Interestingly, redundancy
reduction can be near-optimal when the number of encoding units is limited, such
as in the peripheral retina. We show that there exist multiple, equally-optimal
solutions whose receptive field structure and organization vary significantly.
Among these, the one which maximizes the spatial locality of the computation, but
not the sparsity of either synaptic weights or neural responses, is consistent
with known basic properties of retinal receptive fields. The model further
predicts that receptive field structure changes less with light adaptation at
higher input-to-output cell ratios, such as in the periphery.
PMID- 25121491
TI - Is Plasmodium vivax malaria a severe malaria?: a systematic review and meta
analysis.
AB - BACKGROUND: Plasmodium vivax is one of the major species of malaria infecting
humans. Although emphasis on P. falciparum is appropriate, the burden of vivax
malaria should be given due attention. This study aimed to synthesize the
evidence on severe malaria in P. vivax infection compared with that in P.
falciparum infection. METHODS/PRINCIPAL FINDINGS: We searched relevant studies in
electronic databases. The main outcomes required for inclusion in the review were
mortality, severe malaria (SM) and severe anaemia (SA). The methodological
quality of the included studies was assessed using the Newcastle-Ottawa Scale.
Overall, 26 studies were included. The main meta-analysis was restricted to the
high quality studies. Eight studies (n = 27490) compared the incidence of SM
between P. vivax infection and P. falciparum mono-infection; a comparable
incidence was found in infants (OR: 0.45, 95% CI:0.04-5.68, I2:98%), under 5 year
age group (OR: 2.06, 95% CI: 0.83-5.1, I2:83%), the 5-15 year-age group (OR: 0.6,
95% CI: 0.31-1.16, I2:81%) and adults (OR: 0.83, 95% CI: 0.67-1.03, I2:25%). Six
studies reported the incidences of SA in P. vivax infection and P. falciparum
mono-infection; a comparable incidence of SA was found among infants (OR: 3.47,
95%:0.64-18.94, I2: 92%), the 5-15 year-age group (OR:0.71, 95% CI: 0.06-8.57,
I2:82%). This was significantly lower in adults (OR:0.75, 95% CI: 0.62-0.92,
I2:0%). Five studies (n = 71079) compared the mortality rate between vivax
malaria and falciparum malaria. A lower rate of mortality was found in infants
with vivax malaria (OR:0.61, 95% CI:0.5-0.76, I2:0%), while this was comparable
in the 5-15 year- age group (OR: 0.43, 95% CI:0.06-2.91, I2:84%) and the children
of unspecified-age group (OR: 0.77, 95% CI:0.59-1.01, I2:0%). CONCLUSION:
Overall, the present analysis identified that the incidence of SM in patients
infected with P. vivax was considerable, indicating that P. vivax is a major
cause of SM. Awareness of the clinical manifestations of vivax malaria should
prompt early detection. Subsequent treatment and monitoring of complications can
be life-saving.
PMID- 25121493
TI - Hyperglycemia and blood pressure treatment goal: a cross sectional survey of
18350 patients with type 2 diabetes in 77 tertiary hospitals in China.
AB - OBJECTIVE: To investigate the association of hyperglycemia with blood pressure
control goal in the patients with type 2 diabetes (T2D) cared by tertiary
hospitals in China. STUDY DESIGN AND METHODS: A cross sectional survey of 29442
patients was conducted in 77 tertiary hospitals in 4 major cities in China in
2011 and 18350 of them without known hypertension were used in the analysis.
Univariable and multivariable logistic regression analysis stratified on cities
and hospitals was performed to obtain odds ratio of factors of interest for
achievement of the blood pressure treatment goal, i.e., 140/80 mmHg as
recommended by American Diabetes Association (ADA). Sensitivity analysis was
performed after re-inclusion of 11902 patients with diagnosed hypertension.
Findings from were further replicated in patients with T2D recruited using the
same protocol from tertiary hospitals located in other central cities in China.
RESULTS: The mean age was 58.2 (SD: 11.3) years and 53.3% were male, with a
median of 4 years of disease duration. A total of 12129 patients (58.2%) did not
achieve the ADA recommended goal for BP control. After adjusting for covariables,
hyperglycemia was associated with failure to achieve the BP goal (OR of HbA1c at
6.5%-6.9% vs. <6.0%: 1.22, 95%CI: 1.08 to 1.39; OR of 7.0%-7.0% vs. <6.0%: 1.37,
1.21 to 1.54 and OR of >= 8.0% vs. <6.0%: 1.22, 95%CI: 1.08 to 1.38). The
sensitivity analysis and the replication analysis showed similar results.
CONCLUSIONS: Hyperglycemia defined as HbA1c >= 6.5% increased the risk of failure
to achieve the BP goal in T2D patients.
PMID- 25121495
TI - Phylobetadiversity among forest types in the Brazilian Atlantic Forest complex.
AB - Phylobetadiversity is defined as the phylogenetic resemblance between communities
or biomes. Analyzing phylobetadiversity patterns among different vegetation
physiognomies within a single biome is crucial to understand the historical
affinities between them. Based on the widely accepted idea that different forest
physiognomies within the Southern Brazilian Atlantic Forest constitute different
facies of a single biome, we hypothesize that more recent phylogenetic nodes
should drive phylobetadiversity gradients between the different forest types
within the Atlantic Forest, as the phylogenetic divergence among those forest
types is biogeographically recent. We compiled information from 206 checklists
describing the occurrence of shrub/tree species across three different forest
physiognomies within the Southern Brazilian Atlantic Forest (Dense, Mixed and
Seasonal forests). We analyzed intra-site phylogenetic structure (phylogenetic
diversity, net relatedness index and nearest taxon index) and phylobetadiversity
between plots located at different forest types, using five different methods
differing in sensitivity to either basal or terminal nodes (phylogenetic fuzzy
weighting, COMDIST, COMDISTNT, UniFrac and Rao's H). Mixed forests showed higher
phylogenetic diversity and overdispersion than the other forest types.
Furthermore, all forest types differed from each other in relation
phylobetadiversity patterns, particularly when phylobetadiversity methods more
sensitive to terminal nodes were employed. Mixed forests tended to show higher
phylogenetic differentiation to Dense and Seasonal forests than these latter from
each other. The higher phylogenetic diversity and phylobetadiversity levels found
in Mixed forests when compared to the others likely result from the
biogeographical origin of several taxa occurring in these forests. On one hand,
Mixed forests shelter several temperate taxa, like the conifers Araucaria and
Podocarpus. On the other hand, tropical groups, like Myrtaceae, are also very
representative of this forest type. We point out to the need of more attention to
Mixed forests as a conservation target within the Brazilian Atlantic Forest given
their high phylogenetic uniqueness.
PMID- 25121496
TI - Corneal viscoelastic properties from finite-element analysis of in vivo air-puff
deformation.
AB - Biomechanical properties are an excellent health marker of biological tissues,
however they are challenging to be measured in-vivo. Non-invasive approaches to
assess tissue biomechanics have been suggested, but there is a clear need for
more accurate techniques for diagnosis, surgical guidance and treatment
evaluation. Recently air-puff systems have been developed to study the dynamic
tissue response, nevertheless the experimental geometrical observations lack from
an analysis that addresses specifically the inherent dynamic properties. In this
study a viscoelastic finite element model was built that predicts the
experimental corneal deformation response to an air-puff for different
conditions. A sensitivity analysis reveals significant contributions to corneal
deformation of intraocular pressure and corneal thickness, besides corneal
biomechanical properties. The results show the capability of dynamic imaging to
reveal inherent biomechanical properties in vivo. Estimates of corneal
biomechanical parameters will contribute to the basic understanding of corneal
structure, shape and integrity and increase the predictability of corneal
surgery.
PMID- 25121499
TI - NICE supports allowing technology assessment bodies to provide advice to drug
industry.
PMID- 25121498
TI - Variation in the fitness effects of mutations with population density and size in
Escherichia coli.
AB - The fitness effects of mutations are context specific and depend on both external
(e.g., environment) and internal (e.g., cellular stress, genetic background)
factors. The influence of population size and density on fitness effects are
unknown, despite the central role population size plays in the supply and
fixation of mutations. We addressed this issue by comparing the fitness of 92
Keio strains (Escherichia coli K12 single gene knockouts) at comparatively high
(1.2*10(7) CFUs/mL) and low (2.5*10(2) CFUs/mL) densities, which also differed in
population size (high: 1.2*10(8); low: 1.25*10(3)). Twenty-eight gene deletions
(30%) exhibited a fitness difference, ranging from 5 to 174% (median: 35%),
between the high and low densities. Our analyses suggest this variation among
gene deletions in fitness responses reflected in part both gene orientation and
function, of the gene properties we examined (genomic position, length,
orientation, and function). Although we could not determine the relative effects
of population density and size, our results suggest fitness effects of mutations
vary with these two factors, and this variation is gene-specific. Besides being a
mechanism for density-dependent selection (r-K selection), the dependence of
fitness effects on population density and size has implications for any
population that varies in size over time, including populations undergoing
evolutionary rescue, species invasions into novel habitats, and cancer
progression and metastasis. Further, combined with recent advances in
understanding the roles of other context-specific factors in the fitness effects
of mutations, our results will help address theoretical and applied biological
questions more realistically.
PMID- 25121497
TI - Schistosome feeding and regurgitation.
AB - Schistosomes are parasitic flatworms that infect >200 million people worldwide,
causing the chronic, debilitating disease schistosomiasis. Unusual among
parasitic helminths, the long-lived adult worms, continuously bathed in blood,
take up nutrients directly across the body surface and also by ingestion of blood
into the gut. Recent proteomic analyses of the body surface revealed the presence
of hydrolytic enzymes, solute, and ion transporters, thus emphasising its
metabolic credentials. Furthermore, definition of the molecular mechanisms for
the uptake of selected metabolites (glucose, certain amino acids, and water)
establishes it as a vital site of nutrient acquisition. Nevertheless, the amount
of blood ingested into the gut per day is considerable: for males ~100 nl; for
the more actively feeding females ~900 nl, >4 times body volume. Ingested
erythrocytes are lysed as they pass through the specialized esophagus, while
leucocytes become tethered and disabled there. Proteomics and transcriptomics
have revealed, in addition to gut proteases, an amino acid transporter in gut
tissue and other hydrolases, ion, and lipid transporters in the lumen,
implicating the gut as the site for acquisition of essential lipids and inorganic
ions. The surface is the principal entry route for glucose, whereas the gut
dominates amino acid acquisition, especially in females. Heme, a potentially
toxic hemoglobin degradation product, accumulates in the gut and, since
schistosomes lack an anus, must be expelled by the poorly understood process of
regurgitation. Here we place the new observations on the proteome of body surface
and gut, and the entry of different nutrient classes into schistosomes, into the
context of older studies on worm composition and metabolism. We suggest that the
balance between surface and gut in nutrition is determined by the constraints of
solute diffusion imposed by differences in male and female worm morphology. Our
conclusions have major implications for worm survival under immunological or
pharmacological pressure.
PMID- 25121501
TI - Hypertrophic chondrocytes in the rabbit growth plate can proliferate and
differentiate into osteogenic cells when capillary invasion is interposed by a
membrane filter.
AB - The fate of hypertrophic chondrocytes during endochondral ossification remains
controversial. It has long been thought that the calcified cartilage is invaded
by blood vessels and that new bone is deposited on the surface of the eroded
cartilage by newly arrived cells. The present study was designed to determine
whether hypertrophic chondrocytes were destined to die or could survive to
participate in new bone formation. In a rabbit experiment, a membrane filter with
a pore size of 1 um was inserted in the middle of the hypertrophic zone of the
distal growth plate of ulna. In 33 of 37 animals, vascular invasion was
successfully interposed by the membrane filter. During 8 days, the cartilage
growth plate was enlarged, making the thickness 3-fold greater than that of the
nonoperated control side. Histological examination demonstrated that the
hypertrophic zone was exclusively elongated. At the terminal end of the growth
plate, hypertrophic chondrocytes extruded from their territorial matrix into the
open cavity on the surface of the membrane filter. The progenies of hypertrophic
chondrocytes (PHCs) were PCNA positive and caspase-3 negative. In situ
hybridization studies demonstrated that PHCs did not express cartilage matrix
proteins anymore but expressed bone matrix proteins. Immunohistochemical studies
also demonstrated that the new matrix produced by PHCs contained type I collagen,
osteonectin, and osteocalcin. Based on these results, we concluded that
hypertrophic chondrocytes switched into bone-forming cells after vascular
invasion was interposed in the normal growth plate.
PMID- 25121500
TI - The relationship between muscle fiber type-specific PGC-1alpha content and
mitochondrial content varies between rodent models and humans.
AB - PGC-1alpha regulates critical processes in muscle physiology, including
mitochondrial biogenesis, lipid metabolism and angiogenesis. Furthermore, PGC
1alpha was suggested as an important regulator of fiber type determination.
However, whether a muscle fiber type-specific PGC-1alpha content exists, whether
PGC-1alpha content relates to basal levels of mitochondrial content, and whether
such relationships are preserved between humans and classically used rodent
models are all questions that have been either poorly addressed or never
investigated. To address these issues, we investigated the fiber type-specific
content of PGC-1alpha and its relationship to basal mitochondrial content in
mouse, rat and human muscles using in situ immunolabeling and histochemical
methods on muscle serial cross-sections. Whereas type IIa fibers exhibited the
highest PGC-1alpha in all three species, other fiber types displayed a hierarchy
of type IIx>I>IIb in mouse, type I = IIx> IIb in rat, and type IIx>I in human. In
terms of mitochondrial content, we observed a hierarchy of IIa>IIx>I>IIb in
mouse, IIa >I>IIx> IIb in rat, and I>IIa> IIx in human skeletal muscle. We also
found in rat skeletal muscle that type I fibers displayed the highest
capillarization followed by type IIa >IIx>IIb. Finally, we found in human
skeletal muscle that type I fibers display the highest lipid content, followed by
type IIa>IIx. Altogether, our results reveal that (i) the fiber type-specific PGC
1alpha and mitochondrial contents were only matched in mouse, (ii) the patterns
of PGC-1alpha and mitochondrial contents observed in mice and rats do not
correspond to that seen in humans in several respects, and (iii) the classical
phenotypes thought to be regulated by PGC-1alpha do not vary exclusively as a
function of PGC-1alpha content in rat and human muscles.
PMID- 25121502
TI - Transcriptional regulation of the tumor suppressor FHL2 by p53 in human kidney
and liver cells.
AB - Four and a Half LIM protein 2 (FHL2) is a LIM domain only protein that is able to
form various protein complexes and regulate gene transcription. Recent findings
showed that FHL2 is a potential tumor suppressor gene that was down-regulated in
hepatocellular carcinoma (HCC). Moreover, FHL2 can bind to and activate the TP53
promoter in hepatic cells. In this study, the activity of the two promoters of
FHL2, 1a and 1b, were determined in the human embryonic kidney cell line HEK293
and the activation of these two promoters by p53 was investigated. Our results
showed that the 1b promoter has a higher activity than the 1a promoter in HEK 293
cells but the 1a promoter is more responsive to the activation by p53 when
compared with the 1b promoter. The regulation of FHL2 by p53 was further
confirmed in liver cells by the overexpression of p53 in Hep3B cells and the
knockdown of p53 in HepG2 cells. Combining promoter activity results of truncated
mutants and predictions by bioinformatics tools, a putative p53 binding site was
found in the exon 1a of FHL2 from +213 to +232. The binding between the p53
protein and the putative p53 binding site was then validated by the ChIP assay.
Furthermore, the expression of FHL2 and TP53 were down-regulated in majority of
HCC tumour samples (n = 41) and significantly correlated (P = 0.026). Finally, we
found that the somatic mutation 747 (G->T), a hot spot mutation of the TP53 gene,
is potentially associated with a higher expression of FHL2 in HCC tumour samples.
Taken together, this is the first in-depth study about the transcriptional
regulation of FHL2 by p53.
PMID- 25121503
TI - Low intensity, high frequency vibration training to improve musculoskeletal
function in a mouse model of Duchenne muscular dystrophy.
AB - The objective of the study was to determine if low intensity, high frequency
vibration training impacted the musculoskeletal system in a mouse model of
Duchenne muscular dystrophy, relative to healthy mice. Three-week old wildtype (n
= 26) and mdx mice (n = 22) were randomized to non-vibrated or vibrated (45 Hz
and 0.6 g, 15 min/d, 5 d/wk) groups. In vivo and ex vivo contractile function of
the anterior crural and extensor digitorum longus muscles, respectively, were
assessed following 8 wks of vibration. Mdx mice were injected 5 and 1 days prior
to sacrifice with Calcein and Xylenol, respectively. Muscles were prepared for
histological and triglyceride analyses and subcutaneous and visceral fat pads
were excised and weighed. Tibial bones were dissected and analyzed by micro
computed tomography for trabecular morphometry at the metaphysis, and cortical
geometry and density at the mid-diaphysis. Three-point bending tests were used to
assess cortical bone mechanical properties and a subset of tibiae was processed
for dynamic histomorphometry. Vibration training for 8 wks did not alter
trabecular morphometry, dynamic histomorphometry, cortical geometry, or
mechanical properties (P >= 0.34). Vibration did not alter any measure of muscle
contractile function (P >= 0.12); however the preservation of muscle function and
morphology in mdx mice indicates vibration is not deleterious to muscle lacking
dystrophin. Vibrated mice had smaller subcutaneous fat pads (P = 0.03) and higher
intramuscular triglyceride concentrations (P = 0.03). These data suggest that
vibration training at 45 Hz and 0.6 g did not significantly impact the tibial
bone and the surrounding musculature, but may influence fat distribution in mice.
PMID- 25121505
TI - Pleiotropic effects of a methyl donor diet in a novel animal model.
AB - Folate and other methyl-donor pathway components are widely supplemented due to
their ability to prevent prenatal neural tube defects. Several lines of evidence
suggest that these supplements act through epigenetic mechanisms (e.g. altering
DNA methylation). Primary among these are the experiments on the mouse viable
yellow allele of the agouti locus (A(vy)). In the Avy allele, an Intracisternal A
particle retroelement has inserted into the genome adjacent to the agouti gene
and is preferentially methylated. To further test these effects, we tested the
same diet used in the Avy studies on wild-derived Peromyscus maniculatus, a
native North American rodent. We collected tissues from neonatal offspring whose
parents were fed the high-methyl donor diet as well as controls. In addition, we
assayed coat-color of a natural variant (wide-band agouti = A(Nb)) that
overexpresses agouti as a phenotypic biomarker. Our data indicate that these
dietary components affected agouti protein production, despite the lack of a
retroelement at this locus. Surprisingly, the methyl-donor diet was associated
with defects (e.g. ovarian cysts, cataracts) and increased mortality. We also
assessed the effects of the diet on behavior: We scored animals in open field and
social interaction tests. We observed significant increases in female repetitive
behaviors. Thus these data add to a growing number of studies that suggest that
these ubiquitously added nutrients may be a human health concern.
PMID- 25121507
TI - We are both doctors: a Palestinian doctor writes to an Israeli colleague.
PMID- 25121504
TI - Phosphorylation of a central clock transcription factor is required for thermal
but not photic entrainment.
AB - Transcriptional/translational feedback loops drive daily cycles of expression in
clock genes and clock-controlled genes, which ultimately underlie many of the
overt circadian rhythms manifested by organisms. Moreover, phosphorylation of
clock proteins plays crucial roles in the temporal regulation of clock protein
activity, stability and subcellular localization. dCLOCK (dCLK), the master
transcription factor driving cyclical gene expression and the rate-limiting
component in the Drosophila circadian clock, undergoes daily changes in
phosphorylation. However, the physiological role of dCLK phosphorylation is not
clear. Using a Drosophila tissue culture system, we identified multiple
phosphorylation sites on dCLK. Expression of a mutated version of dCLK where all
the mapped phospho-sites were switched to alanine (dCLK-15A) rescues the
arrythmicity of Clk(out) flies, yet with an approximately 1.5 hr shorter period.
The dCLK-15A protein attains substantially higher levels in flies compared to the
control situation, and also appears to have enhanced transcriptional activity,
consistent with the observed higher peak values and amplitudes in the mRNA
rhythms of several core clock genes. Surprisingly, the clock-controlled daily
activity rhythm in dCLK-15A expressing flies does not synchronize properly to
daily temperature cycles, although there is no defect in aligning to light/dark
cycles. Our findings suggest a novel role for clock protein phosphorylation in
governing the relative strengths of entraining modalities by adjusting the
dynamics of circadian gene expression.
PMID- 25121506
TI - Folliculin regulates cell-cell adhesion, AMPK, and mTORC1 in a cell-type-specific
manner in lung-derived cells.
AB - Germline loss-of-function BHD mutations cause cystic lung disease and hereditary
pneumothorax, yet little is known about the impact of BHD mutations in the lung.
Folliculin (FLCN), the product of the Birt-Hogg-Dube (BHD) gene, has been linked
to altered cell-cell adhesion and to the AMPK and mTORC1 signaling pathways. We
found that downregulation of FLCN in human bronchial epithelial (HBE) cells
decreased the phosphorylation of ACC, a marker of AMPK activation, while
downregulation of FLCN in small airway epithelial (SAEC) cells increased the
activity of phospho-S6, a marker of mTORC1 activation, highlighting the cell type
dependent functions of FLCN. Cell-cell adhesion forces were significantly
increased in FLCN-deficient HBE cells, consistent with prior findings in FLCN
deficient human kidney-derived cells. To determine how these altered cell-cell
adhesion forces impact the lung, we exposed mice with heterozygous inactivation
of Bhd (similarly to humans with germline inactivation of one BHD allele) to
mechanical ventilation at high tidal volumes. Bhd(+/-) mice exhibited a trend (P
= 0.08) toward increased elastance after 6 h of ventilation at 24 cc/kg. Our
results indicate that FLCN regulates the AMPK and mTORC1 pathways and cell-cell
adhesion in a cell type-dependent manner. FLCN deficiency may impact the
physiologic response to inflation-induced mechanical stress, but further
investigation is required. We hypothesize that FLCN-dependent effects on
signaling and cellular adhesion contribute to the pathogenesis of cystic lung
disease in BHD patients.
PMID- 25121508
TI - Changes in corneal deformation parameters after lenticule creation and extraction
during small incision lenticule extraction (SMILE) procedure.
AB - PURPOSE: To investigate the effects of lenticule creation and subsequent corneal
lenticule extraction on corneal deformation parameters during small incision
lenticule extraction (SMILE) procedure. MATERIALS AND METHODS: In this
prospective study, 18 eyes of 10 patients (27.90 +/- 7.11 years, -5.64 +/- 2.45
diopters) scheduled for SMILE procedure were enrolled. Changes in the corneal
deformation parameters, including deformation amplitude (DA), applanation
time(AT1 and AT2), applanation length(AL1 and AL2), corneal velocity(CV1 and
CV2), peak distance(P.Dist.), radius and intraocular pressure values were
measured preoperatively, immediately after lenticule creation and subsequent to
corneal lenticule extraction in all eyes with the Corvis Scheimpflug Technology
(Corvis ST, OCULUS, Wetzlar, Germany). Repeated measures analysis of variance
(ANOVA) with bonferroni-adjusted post hoc comparisons was performed to
investigate changes following each step of the procedure. RESULTS: All surgical
procedures were uneventful. A significant difference was detected among the three
time points (pre-operation, post-lenticule creation and post lenticule
extraction) for AT1 (P<0.001), AT2 (P = 0.001), DA(P<0.001), and IOP(P = 0.002).
Bonferroni-adjusted post hoc comparisons indicated that there was no significant
change in AT1, AT2, DA, or IOP after lenticule creation (post hoc P>0.05), but
there was a significant change in these parameters following subsequent corneal
lenticule extraction (post hoc P<0.01), when compared to values obtained pre
operatively. The scheimpflug camera of the Corvis ST demonstrated the
intralamellar small gas bubbles formed from the vaporisation of tissue after
lenticule creation and a gray zone was observed between the cap and the residual
stromal bed after lenticule extraction. CONCLUSIONS: There is a significant
change in corneal deformation parameters following SMILE procedure. The changes
may be caused predominantly by stromal lenticule extraction, while lenticule
creation with femtosecond laser may not have an obvious effect on corneal
deformation properties.
PMID- 25121509
TI - Intraosseous fixation compared to plantar plate fixation for first
metatarsocuneiform arthrodesis: a cadaveric biomechanical analysis.
AB - BACKGROUND: Metatarsocuneiform (MTC) fusion is a treatment option for management
of hallux valgus. We compared the biomechanical characteristics of an internal
fixation device with plantar plate fixation. METHODS: Seven matched pairs of feet
from human cadavers were used to compare the intramedullary (IM) device plus
compression screw to plantar plate combined with a compression screw. Specimen
constructs were loaded in a cyclic 4-point bending test. We obtained
initial/final stiffness, maximum load, and number of cycles to failure. Bone
mineral density was measured with peripheral quantitative computed tomography.
Performance was compared using time to event analysis with number of cycles as
time variable, and a proportional hazard model including shared frailty model
fitted with treatment and bone mineral density as covariates. RESULTS: On average
the plates failed after 7517 cycles and a maximum load of 167 N, while the IM
implants failed on average after 2946 cycles and a maximum load of 69 N. In all
pairs the 1 treated with IM-implant failed earlier than the 1 treated with a
plate (hazard ratio for IM-implant versus plate was 79.9 (95% confidence interval
[6.1, 1052.2], P = .0009). The initial stiffness was 131 N/mm for the plantar
plate and 43.3 N/mm for the IM implant. Initial stiffness (r = .955) and final
stiffness (r = .952) were strongly related to the number of cycles to failure.
Bone mineral density had no effect on the number of cycles to failure.
CONCLUSION: Plantar plate fixation created a stronger and stiffer construct than
IM fixation. CLINICAL RELEVANCE: A stiffer construct can reduce the risk of
nonunion and shorten the period of non-weight-bearing.
PMID- 25121510
TI - Early results with LifeStent implantation in RESILIENT and non-RESILIENT
inclusion criteria patients.
AB - The purpose of our study was to determine outcomes of patients receiving the
LifeStent (Bard Peripheral Vascular, Tempe, AZ) for femoropopliteal peripheral
arterial disease in real-world academic practice outside the limitations of an
industry supported trial. All patients from 2009 to 2012 at our institution who
received a LifeStent during endovascular interventions and had follow-up were
included. Outcomes evaluated included patency and freedom from limb loss. A total
of 166 limbs in 151 patients had the LifeStent implanted in de novo vessels (54%
male; 68 +/- 12 years). Eighty-percent of limbs did not meet RESILIENT criteria
due to Rutherford category >3 (51%), TransAtlantic Inter-Society Consensus II
classifications C/ D (51%), zero runoff vessels (6%), or stent location (17%).
Primary patency rates were 81% at 6 months and 58% at 12 months with predictors
for primary patency loss at 1 year including Rutherford category >3 (HR: 1.8 (95%
CI: 1.0-3.1), p = 0.04), tobacco use (HR: 1.8 (95% CI: 1.0-3.3), p = 0.04), and
no clopidogrel at discharge (HR: 3.2 (95% CI: 1.6-6.7), p < 0.01). A
preintervention Rutherford category >3 predicted 24-month limb loss (HR, 16.0
(95% CI: 2.0-122.0), p < 0.01). The LifeStent is a viable option regardless of
the TransAtlantic Inter-Society Consensus II classification; however, critical
limb ischemia, current tobacco use, and absence of clopidogrel on discharge
predict decreased patency on follow-up.
PMID- 25121512
TI - Diabetes prescribing in England consumes nearly 10% of primary care budget.
PMID- 25121511
TI - Developing an internationally-applicable service specification for continence
care: systematic review, evidence synthesis and expert consensus.
AB - BACKGROUND: Global demographic trends suggest that the incidence of both urinary
and faecal incontinence will rise in the coming years, bringing significant
health and economic implications for both patients and payers. There is limited
organisational evidence to guide payers and providers about service configuration
which will deliver efficient guideline-compliant, high-quality patient care.
OBJECTIVES: To create, using evidence from a systematic review, qualitative data
and expert consensus an internationally applicable service specification for
continence care. METHOD: Evidence was obtained from a systematic and grey
literature review of published randomised controlled trials and quasi
experimental studies reporting efficacy of continence service design at the level
of the community dwelling patient with either bladder or bowel incontinence,
governmental reports and policy frameworks supplemented by data from 47 semi
structured interviews with clinicians, patients, patient-representatives and
policy experts from four geographies broadly representative of different
healthcare systems. RESULTS: A number of themes related to current and potential
future organisation of continence care were identified from the data. A modular
service specification with eight core components was created including case
detection, initial assessment and treatment, case co-ordination, caregiver
support, community-based support, specialist assessment and treatment, use of
containment products, and use of technology. Within this framework important key
recommendations are: ensure robust referral pathways, shift assessment for case
coordination to nurses specializing in continence care, promote self-management
and technology, use comprehensive assessment tools and service performance
targets based on outcome and operational measures. CONCLUSIONS: This study has
defined practice gaps in the provision of continence services and described eight
core components of a service specification for incontinence that commissioners
and payers of health and social care could consider using to provide high-quality
continence care. A shift towards a community-delivered, nurse-led model appears
to be associated with clinical and cost-effective care for people with bladder
and bowel incontinence.
PMID- 25121514
TI - The development of the pediatric NAFLD fibrosis score (PNFS) to predict the
presence of advanced fibrosis in children with nonalcoholic fatty liver disease.
AB - BACKGROUND: Noninvasive hepatic fibrosis scores that predict the presence of
advanced fibrosis have been developed and validated in adult patients with NAFLD.
The aims of our study were to assess the utility of commonly used adult fibrosis
scores in pediatric NAFLD and to develop a pediatric specific fibrosis score that
can predict advanced fibrosis. METHODS: Consecutive children with biopsy-proven
NAFLD were included. Fibrosis was determined by an experienced pathologist (F0
4). Advanced fibrosis was defined as fibrosis stage >= 3. The following adult
fibrosis scores were calculated for each child: AST/ALT ratio, AST/platelet ratio
index (APRI), NAFLD fibrosis score (NFS), and FIB-4 Index. Multivariable logistic
regression analysis was performed to build a new pediatric model for predicting
advanced fibrosis. RESULTS: Our cohort consisted of 242 children with a mean age
of 12.4 +/- 3.1 years and 63% were female. 36 (15%) subjects had advanced
fibrosis. APRI and FIB-4 were higher in patients with advanced fibrosis compared
to those with fibrosis stage 0-2; however, AST/ALT ratio and NFS were not
different between the two groups. We used our data to develop a new model to
predict advanced fibrosis which included: ALT, alkaline phosphatase, platelet
counts and GGT. The multivariable logistic regression model (z) was defined as
follows: z = 1.1+(0.34*sqrt(ALT))+(0.002*alkaline phosphatase) -
(1.1*log(platelets) - (0.02*GGT). This value was then converted into a
probability distribution (p) with a value between 0 to 100 by the following
formula: p = 100 * exp(z)/[1+exp(z)]. The AUCROC for this model was 0.74 (95% CI:
0.66, 0.82). This was found to be significantly better than APRI, NAFLD Fibrosis
Score and FIB-4 Index. CONCLUSION: Noninvasive hepatic fibrosis scores developed
in adults had poor performance in diagnosing advanced fibrosis in children with
NAFLD. We developed a new pediatric NAFLD fibrosis score with improved
performance characteristics.
PMID- 25121515
TI - Toxic peptides occur frequently in pergid and argid sawfly larvae.
AB - Toxic peptides containing D-amino acids are reported from the larvae of sawfly
species. The compounds are suspected to constitute environmental contaminants, as
they have killed livestock grazing in areas with congregations of such larvae,
and related larval extracts are deleterious to ants. Previously, two octapeptides
(both called lophyrotomin) and three heptapeptides (pergidin, 4-valinepergidin
and dephosphorylated pergidin) were identified from three species in the family
Pergidae and one in Argidae. Here, the hypothesis of widespread occurrence of
these peptides among sawflies was tested by LC-MS analyses of single larvae from
eight pergid and 28 argid species, plus nine outgroup species. At least two of
the five peptides were detected in most sawfly species, whereas none in any
outgroup taxon. Wherever peptides were detected, they were present in each
examined specimen of the respective species. Some species show high peptide
concentrations, reaching up to 0.6% fresh weight of 4-valinepergidin (1.75
mg/larva) in the pergid Pterygophorus nr turneri. All analyzed pergids in the
subfamily Pterygophorinae contained pergidin and 4-valinepergidin, all argids in
Arginae contained pergidin and one of the two lophyrotomins, whereas none of the
peptides was detected in any Perginae pergid or Sterictiphorinae argid (except in
Schizocerella pilicornis, which contained pergidin). Three of the four sawfly
species that were previously known to contain toxins were reanalyzed here,
resulting in several, often strong, quantitative and qualitative differences in
the chemical profiles. The most probable ecological role of the peptides is
defense against natural enemies; the poisoning of livestock is an epiphenomenon.
PMID- 25121516
TI - Distance-dependent association of affect with pacing strategy in cycling time
trials.
AB - The psychological construct of affect is proposed to significantly contribute to
pacing decisions during exercise. Borg's RPE scale, another important regulator
of work rate, is criticized as an inadequate measure of the multiple perceptual
responses experienced. This study aimed to examine power output distribution and
associated changes in affect, self-efficacy, perceptual cues, HR, and respiratory
gases during both 16.1- and 40-km self-paced cycling time trials (TT). Secondly,
the differentiation between physical perceptions of exertion and sense of effort
in self-paced exercise was investigated. METHOD: Fifteen trained male cyclists
completed 16.1- and 40-km TT using a CompuTrainer cycle ergometer. Time, power
output distribution, affect, self-efficacy, physical RPE (P-RPE), task effort and
awareness (TEA), HR, and respiratory gases were measured throughout each TT.
Linear mixed models explored associations of these variables with power output
distribution and the relationship between P-RPE and TEA. RESULTS: Similar pacing
strategies were adopted in the 16.1- and 40-km TT (P = 0.31), and the main
effects were found for affect (P = 0.001) and RER (P < 0.001). Interactions
between affect (P = 0.037) and RER (P = 0.004), with condition, indicated closer
associations with power output distribution in 16.1 km than that in 40 km TT. P
RPE was not significantly different from TEA (P = 0.053). CONCLUSION: A
significant association between affect and power output distribution suggests
that affective responses are task dependent even in self-paced exercise, and a
greater association is demonstrated in higher intensity, 16.1 km TT. Furthermore,
physical perceptions of exertion are not clearly differentiated from the sense of
effort in self-paced exercise.
PMID- 25121517
TI - Comparison of step outputs for waist and wrist accelerometer attachment sites.
AB - PURPOSE: The objective of this study is to compare step outputs obtained from
waist and wrist accelerometer attachment sites under laboratory and free-living
conditions. METHODS: Under the laboratory condition, participants concurrently
wore ActiGraph accelerometers at their waist and nondominant wrist while
walking/running at treadmill speeds between 14 and 188 m.min. Visually counted
steps served as a criterion standard. Participants then wore both accelerometers
for 7 d. All accelerometer step data were processed applying both the
manufacturer's default and low-frequency extension filters. Paired sample t-tests
were used to evaluate mean differences in criterion steps per minute and the four
(attachment site * filter) estimates produced from the waist- and wrist-worn
accelerometers in the laboratory study. Free-living differences in mean steps per
day detected between the waist and wrist (considering both filters) were
computed. RESULTS: Relative to visually counted steps, the waist attachment site
generally outperformed the wrist attachment site at most speeds, regardless of
the applied filtering process. Under free-living conditions, the waist-worn
accelerometer detected 6743 +/- 2398 (default filter) and 13,029 +/- 3734 (low
frequency extension) steps per day. The concurrently worn wrist accelerometer
detected 9301 +/- 2887 (default filter) and 15,493 +/- 3958 (low-frequency
extension) steps per day. CONCLUSION: The wrist attachment site detected
consistently fewer visually counted steps than the waist attachment site at most
treadmill speeds during laboratory testing. In contrast, the wrist attachment
site produced a higher average step count (ranging from approximately 2500 to
8700 more steps per day under free-living conditions, dependent on the filtering
process applied) than the waist attachment site under free-living conditions. In
conclusion, step outputs obtained from waist- and wrist-worn accelerometer
attachment sites are generally not comparable under either laboratory or free
living conditions.
PMID- 25121513
TI - Comparing interferon-gamma release assays to tuberculin skin test in Thai
children with tuberculosis exposure.
AB - BACKGROUND: Data on the performance of interferon-gamma release assays (IGRAs),
QuantiFERON TB Gold In-tube (QFNGIT) and T-Spot.TB, in diagnosing tuberculosis
(TB) are limited in Southeast Asia. This study aims to compare the performances
of the two IGRAs and TST in Thai children with recent TB exposure. METHODS: This
multicenter, prospective study enrolled children with recent exposure to active
TB adults. Children were investigated for active TB. TST was performed and blood
collected for T-Spot.TB and QFNGIT. RESULTS: 158 children were enrolled (87% TB
exposed and 13% active TB, mean age 7.2 years). Only 3 children had HIV
infection. 66.7% had TST>=10 mm, while 38.6% had TST>=15 mm. 32.5% had positive
QFNGIT; 29.9% had positive T-Spot.TB. QFNGIT and T-Spot.TB positivity was higher
among children with active TB compared with TB-exposed children. No indeterminate
IGRA results were detected. No statistically significant differences between the
performances of the IGRAs and TST at the two cut-offs with increasing TB exposure
were detected. Concordance for positive IGRAs and TST ranged from 42-46% for
TST>=10 mm and 62-67% for TST>=15 mm. On multivariable analyses, exposure to
household primary/secondary caregiver with TB was associated with positive
QFNGIT. Higher TB contact score and active TB were associated with positive T
Spot.TB. CONCLUSIONS: Both QFNGIT and T-Spot.TB performed well in our Thai
pediatric study population. No differences in the performances between tests with
increasing TB exposure were found. Due to accessibility and low cost, using TST
may more ideal than IGRAs in diagnosing latent and active TB in healthy children
in Thailand and other similar settings.
PMID- 25121518
TI - Myotonic dystrophy: diagnosis, management and new therapies.
AB - PURPOSE OF REVIEW: Myotonic dystrophies type 1 and type 2 are progressive
multisystem genetic disorders with clinical and genetic features in common.
Myotonic dystrophy type 1 is the most prevalent muscular dystrophy in adults and
has a wide phenotypic spectrum. The average age of death in myotonic dystrophy
type 1 is in the fifth decade. In comparison, myotonic dystrophy type 2 tends to
cause a milder phenotype with later onset of symptoms and is less common than
myotonic dystrophy type 1. Historically, patients with myotonic dystrophy type 1
have not received the medical and social input they need to maximize their
quality and quantity of life. This review describes the improved understanding in
the molecular and clinical features of myotonic dystrophy type 1 as well as the
screening of clinical complications and their management. We will also discuss
new potential genetic treatments. RECENT FINDINGS: An active approach to
screening and management of myotonic dystrophies type 1 and type 2 requires a
multidisciplinary medical, rehabilitative and social team. This process will
probably improve morbidity and mortality for patients. Genetic treatments have
been successfully used in in-vitro and animal models to reverse the
physiological, histopathological and transcriptomic features. SUMMARY: Molecular
therapeutics for myotonic dystrophy will probably bridge the translational gap
between bench and bedside in the near future. There will still be a requirement
for clinical screening of patients with myotonic dystrophy with proactive and
systematic management of complications.
PMID- 25121520
TI - Acute conditions, incidence and associated disability, United States - july 1971
june 1972.
AB - During JuIy 1971-June 1972, an estimated 447,735,000 acute illnesses or injuries
requiring either medical attention or reduced daily activity were experienced by
the civilian, noninstitutionalized population of the United States. The incidence
of new cases of acute conditions per 100 persons per year was 220.2, which is
somewhat larger than the annual incidence rate of 210.1 conditions per 100
persons reported for the previous 12-month period. The increase in the incidence
rate was accounted for primarily by a rise in acute respiratory illnesses from
110.3 per 100 persons in July 1970-June 1971 to 120.7 in July 1971-June 1972. A
notable increase in the incidence rate of influenza-like illnesses for 39.0 to
47.5 was responsible for the most part for the increased incidence rate of acute
respiratory illnesses. This report is one of an annual series of such reports on
the incidence of acute illness or injury based on data collected in the Health
Interview Survey. The last report, Series 10, No. 82, covered the period July
1970-June 1971; acute illness or injury reports in Series 10 are Numbers 1, 10,
15, 26, 38, 44, 54, 69, and 77. The incidence of acute conditions on a calendar
year basis is presented in summary form in the Current Estimates reports Series
10, Numbers 52, 60, 63, 72, 79, and 85 for 1967 through-1972.
PMID- 25121519
TI - cAMP regulates expression of the cyclic nucleotide transporter MRP4 (ABCC4)
through the EPAC pathway.
AB - Multidrug resistance protein 4 (MRP4/ABCC4) has been established as an
independent regulator of cyclic AMP (cAMP) levels particularly in vascular smooth
muscle cells and in hematopoietic cells. Here, we assessed whether cAMP in turn
regulates MRP4. A significant upregulation of MRP4 mRNA and protein by long-term
treatment with cAMP-enhancing agents was observed in HeLa cells, smooth muscle
cells, and megakaryoblastic leukemia M07e cells. This upregulation was not
affected by inhibition of protein kinase A, but could be reverted by inhibitors
and siRNA of an alternative cAMP-signaling route involving exchange proteins
activated by cyclic AMP (EPAC) and mitogen-activated protein kinases. A selective
EPAC activator could equally induce MRP4. The transcriptional regulation was
confirmed in a luciferase reporter gene assay using a vector containing a 1494-bp
fragment of the promoter region of the MRP4/ABCC4 gene. Our results suggest that
enhanced cAMP levels upregulate MRP4 expression, which can result in increased
cAMP efflux.
PMID- 25121522
TI - Stable boron nitride diamondoids as nanoscale materials.
AB - We predict the stability of diamondoids made up of boron and nitrogen instead of
carbon atoms. The results are based on quantum-mechanical calculations within
density functional theory (DFT) and show some very distinct features compared to
the regular carbon-based diamondoids. These features are evaluated with respect
to the energetics and electronic properties of the boron nitride diamondoids as
compared to the respective properties of the carbon-based diamondoids. We find
that BN-diamondoids are overall more stable than their respective C-diamondoid
counterparts. The electronic band-gaps (E(g)) of the former are overall lower
than those for the latter nanostructures but do not show a very distinct trend
with their size. Contrary to the lower C-diamondoids, the BN-diamondoids are
semiconducting and show a depletion of charge on the nitrogen site. Their
differences in the distribution of the molecular orbitals, compared to their
carbon-based counterparts, offer additional bonding and functionalization
possibilities. These tiny BN-based nanostructures could potentially be used as
nanobuilding blocks complementing or substituting the C-diamondoids, based on the
desired properties. An experimental realization of boron nitride diamondoids
remains to show their feasibility.
PMID- 25121523
TI - Electromagnetic modelization of spherical focusing on a one-dimensional grating
thanks to a conical B-spline modal method.
AB - Focusing light onto nanostructures thanks to spherical lenses is a first step in
enhancing the field and is widely used in applications. Nonetheless, the
electromagnetic response of such nanostructures, which have subwavelength
patterns, to a focused beam cannot be described by the simple ray tracing
formalism. Here, we present a method for computing the response to a focused
beam, based on the B-spline modal method adapted to nanostructures in conical
mounting. The eigenmodes are computed in each layer for both polarizations and
are then combined for the computation of scattering matrices. The simulation of a
Gaussian focused beam is obtained thanks to a truncated decomposition into plane
waves computed on a single period, which limits the computation burden.
PMID- 25121521
TI - Child pain catastrophizing mediates the relation between parent responses to pain
and disability in youth with functional abdominal pain.
AB - OBJECTIVES: Functional abdominal pain (FAP) in youth is associated with
substantial impairment in functioning, and prior research has shown that
overprotective parent responses can heighten impairment. Little is known about
how a range of parental behaviors (overprotection, minimizing, and/or
encouragement) in response to their child's pain interact with child coping
characteristics (eg, catastrophizing) to influence functioning in youth with FAP.
In this study, it was hypothesized that the relation between parenting factors
and child disability would be mediated by children's levels of maladaptive coping
(ie, pain catastrophizing). METHODS: Seventy-five patients with FAP presenting to
a pediatric pain clinic and their caregivers participated in the study. Youth
completed measures of pain intensity (Numeric Rating Scale), pain catastrophizing
(Pain Catastrophizing Scale), and disability (Functional Disability Inventory).
Caregivers completed measures of parent pain catastrophizing (Pain
Catastrophizing Scale), and parent responses to child pain behaviors (Adult
Responses to Child Symptoms: Protection, Minimizing, and Encouragement/Monitoring
subscales). RESULTS: Increased functional disability was significantly related to
higher child pain intensity, increased child and parent pain catastrophizing, and
higher levels of encouragement/monitoring and protection. Parent minimization was
not related to disability. Child pain catastrophizing fully mediated the relation
between parent encouragement/monitoring and disability and partially mediated the
relation between parent protectiveness and disability. CONCLUSIONS: The impact of
parenting behaviors in response to FAP on child disability is determined, in
part, by the child's coping style. Findings highlight a more nuanced
understanding of the parent-child interaction in determining pain-related
disability levels, which should be taken into consideration in assessing and
treating youth with FAP.
PMID- 25121524
TI - Projection operator method for biperiodic diffraction gratings with
anisotropic/bianisotropic generalizations.
AB - The "projection operator" method is a variation of the normal-vector method for
simulating optical diffraction from biperiodic gratings. A projection operator
defined by the normal vector is interpolated over the grating volume rather than
interpolating the vector itself. This approach circumvents difficulties
associated with sign reversals and discontinuities encountered with the normal
vector method, and it facilitates implementation for general grating geometries.
The method is readily extensible to anisotropic and bianisotropic materials.
Several numerical examples of the new method are presented, including comparisons
to previously published test cases.
PMID- 25121525
TI - Intrinsic optical torque of cylindrical vector beams on Rayleigh absorptive
spherical particles.
AB - The intrinsic optical torque of a focused cylindrical vector beam on a Rayleigh
absorptive spherical particle is calculated via the corrected dipole
approximation. Numerical results show that, for the radially polarized input
field, the torque is distributed in the focal plane strictly along the azimuthal
direction anywhere except at the focus. This shows a completely different
property from what is observed in the focusing of a circularly polarized beam,
where a strong axial torque component arises. For other cylindrically polarized
input fields, the torque tends to align itself along the radial direction, as the
polarization angle (the angle between the electric vector and the radial
direction) changes from 0 degrees to 90 degrees . When limited to considering
the torque at the equilibrium position, we find that only for those input fields
with polarization angles larger than 50 degrees , the particle experiences a
nonzero torque at its equilibrium position. This is verified by showing
quantitatively the effects of the polarization angle on the magnitude and
orientation of the torque at the equilibrium position.
PMID- 25121526
TI - Realization of hybrid compressive imaging strategies.
AB - The tendency of natural scenes to cluster around low frequencies is not only
useful in image compression, it also can prove advantageous in novel infrared and
hyperspectral image acquisition. In this paper, we exploit this signal model with
two approaches to enhance the quality of compressive imaging as implemented in a
single-pixel compressive camera and compare these results against purely random
acquisition. We combine projection patterns that can efficiently extract the
model-based information with subsequent random projections to form the hybrid
pattern sets. With the first approach, we generate low-frequency patterns via a
direct transform. As an alternative, we also used principal component analysis of
an image library to identify the low-frequency components. We present the first
(to the best of our knowledge) experimental validation of this hybrid signal
model on real data. For both methods, we acquire comparable quality of
reconstructions while acquiring only half the number of measurements needed by
traditional random sequences. The optimal combination of hybrid patterns and the
effects of noise on image reconstruction are also discussed.
PMID- 25121527
TI - Real-time and accurate rail wear measurement method and experimental analysis.
AB - When a train is running on uneven or curved rails, it generates violent
vibrations on the rails. As a result, the light plane of the single-line
structured light vision sensor is not vertical, causing errors in rail wear
measurements (referred to as vibration errors in this paper). To avoid vibration
errors, a novel rail wear measurement method is introduced in this paper, which
involves three main steps. First, a multi-line structured light vision sensor
(which has at least two linear laser projectors) projects a stripe-shaped light
onto the inside of the rail. Second, the central points of the light stripes in
the image are extracted quickly, and the three-dimensional profile of the rail is
obtained based on the mathematical model of the structured light vision sensor.
Then, the obtained rail profile is transformed from the measurement coordinate
frame (MCF) to the standard rail coordinate frame (RCF) by taking the three
dimensional profile of the measured rail waist as the datum. Finally, rail wear
constraint points are adopted to simplify the location of the rail wear points,
and the profile composed of the rail wear points are compared with the standard
rail profile in RCF to determine the rail wear. Both real data experiments and
simulation experiments show that the vibration errors can be eliminated when the
proposed method is used.
PMID- 25121528
TI - Diffraction by nanocrystals II.
AB - Nanocrystals with more than one molecule in the unit cell will generally
crystallize with incomplete unit cells on the crystal surface. Previous results
show that the ensemble-averaged diffraction by such crystals consists of a usual
Bragg component and two other Bragg-like components due to the incomplete unit
cells. Using an intrinsic flexibility in the definition of the incomplete-unit
cell part of a crystal, the problem is formulated such that the magnitude of the
Bragg-like components is minimized, which leads to a simpler and more useful
interpretation of the diffraction. Simulations show the nature of the relative
magnitudes of the diffraction components in different regions of reciprocal space
and the effect of crystal faceting.
PMID- 25121529
TI - High-order integral equation methods for problems of scattering by bumps and
cavities on half-planes.
AB - This paper presents high-order integral equation methods for the evaluation of
electromagnetic wave scattering by dielectric bumps and dielectric cavities on
perfectly conducting or dielectric half-planes. In detail, the algorithms
introduced in this paper apply to eight classical scattering problems, namely,
scattering by a dielectric bump on a perfectly conducting or a dielectric half
plane, and scattering by a filled, overfilled, or void dielectric cavity on a
perfectly conducting or a dielectric half-plane. In all cases field
representations based on single-layer potentials for appropriately chosen Green
functions are used. The numerical far fields and near fields exhibit excellent
convergence as discretizations are refined-even at and around points where
singular fields and infinite currents exist.
PMID- 25121530
TI - Holographic particle sizing and locating by using Hilbert-Huang transform.
AB - By using the Hilbert-Huang transform, a novel method is proposed to perform the
task of particle sizing and axial locating directly from in-line digital
holograms rather than reconstructing the optical field. The intensity
distribution of the particle hologram is decomposed into intrinsic mode functions
(IMFs) by the empirical mode decomposition. From the Hilbert spectrum of these
IMFs, the axial location of the particle can be calculated by fitting the
spectrum to a straight line, and the particle size can be derived from the
singularities of the spectrum. Our method does not need to predefine any basis
function; thus the whole process is fast and efficient. The validity and accuracy
of the method are demonstrated by the numerical simulations and experiments. It
is expected that this method can be used in on-line particle sizing and 3D
tracking.
PMID- 25121531
TI - Coherence filtering and revivals in x-ray waveguides: a communication-modes
approach.
AB - Waveguides for short-wavelength x-rays have been successfully employed for
microbeam and nanobeam production and microscopy experiments. The coherence of
hard x-ray sources is generally poor, and therefore the spatial coherence
filtering characteristics of waveguides have been attractive for high-resolution
microscopy experiments. To quantify the spatial coherence filtering properties of
a waveguide, we here report a theoretical study of the propagation of a partially
coherent beam in a waveguide in the paraxial approximation. By propagating the
cross-spectral density function associated with the partially coherent field, we
quantify in detail the evolution of the spatial coherence as the beam proceeds
along the waveguide. The propagation is efficiently accomplished using the
communication-modes formalism. The generality of the approach makes it suitable
to study more complex phenomena such as the second-order Talbot self-imaging
effect and coherence revivals in waveguides. Numerical results are shown for
waveguides illuminated by partially coherent hard x-rays.
PMID- 25121532
TI - Accelerating propagation properties of misplaced Hermite-Gaussian beams.
AB - A new family of finite-energy accelerating beams was constructed through
misplacing the Hermite polynomial and Gaussian window function. The closed-form
solution of k-space spectra and paraxial propagation of these beams are derived
from the Fourier transform and the scalar angle spectra integral. These beams
have similar propagation properties to finite Airy beams and parabolic beams, but
the accelerating trajectory is hyperbola rather than parabola. The beam family
can be experimentally generated by exponentially truncating the high-order
Hermite-Gaussian beams in the spatial domain.
PMID- 25121533
TI - Optical phase under deep turbulence conditions.
AB - The Markov approximation for waves in random media specifies that, under strong
scintillation conditions, the optical field of unbounded waves has a normal
probability distribution with zero mean. Using the coherence function provided by
the Markov approximation, we calculate statistics of the phase of the optical
field that accounts for the presence of multiple phase dislocations. We also
develop and test a Monte Carlo model that generates the phase samples obeying
these statistics. In contrast to numerous phase models described in the
literature, this model generates discontinuous phase samples that contain optical
vortices.
PMID- 25121534
TI - Scaling perceived saturation.
AB - Two psychophysical experiments were conducted at North Carolina State University
(NCSU) and Rochester Institute of Technology (RIT) to obtain replicated perceived
saturation data from color normal observers on the order of one unit of
saturation. The same 37 Munsell sample sheets, including up to four references
that had similar perceived saturation but different hue, were used in both
experiments. Different assessment methods included presenting either four
references simultaneously or only one reference at a time to observers and
obtaining judged saturation magnitudes for the given Munsell samples. Four
saturation models comprising Sab*, Suv*, CIECAM02, as well as Richter/Lubbe, were
tested. CIECAM02 gave the best prediction of saturation for data obtained at NCSU
while Sab* outperformed other models for the RIT data. For the combined dataset,
Sab*, the Richter/Lubbe, and CIECAM02-based saturation models exhibited
comparable performances. The Standardized Residual Sum of Squares index was used
to measure the inter- and intra-observer variability and goodness of fit. Inter-
and intra-observer variability of assessments was smaller than or comparable to
those reported for the typical color difference evaluation experiments.
PMID- 25121535
TI - Light scattering by three-dimensional objects with semi-hard boundaries.
AB - We introduce analytical models for scattering potentials of particles that have
ellipsoid-, cylinder-, and parallelepiped-like shapes and adjustable edge
sharpness with the help of the three-dimensional versions of the multi-Gaussian
functions. The far fields produced upon scattering from such potentials are
examined in detail and are shown to qualitatively and quantitatively depend on
the scatterer's symmetry type as well as its orientation and edge sharpness.
PMID- 25121536
TI - Backscatter analysis based algorithms for increasing transmission through highly
scattering random media using phase-only-modulated wavefronts.
AB - Recent theoretical and experimental advances have shed light on the existence of
so-called "perfectly transmitting" wavefronts with transmission coefficients
close to 1 in strongly backscattering random media. These perfectly transmitting
eigen-wavefronts can be synthesized by spatial amplitude and phase modulation.
Here, we consider the problem of transmission enhancement using phase-only
modulated wavefronts. Motivated by biomedical applications, in which it is not
possible to measure the transmitted fields, we develop physically realizable
iterative and non-iterative algorithms for increasing the transmission through
such random media using backscatter analysis. We theoretically show that, despite
the phase-only modulation constraint, the non-iterative algorithms will achieve
at least about 25pi%~78.5% transmission with very high probability, assuming that
there is at least one perfectly transmitting eigen-wavefront and that the
singular vectors of the transmission matrix obey the maximum entropy principle
such that they are isotropically random. We numerically analyze the limits of
phase-only-modulated transmission in 2D with fully spectrally accurate simulators
and provide rigorous numerical evidence confirming our theoretical prediction in
random media, with periodic boundary conditions, that is composed of hundreds of
thousands of non-absorbing scatterers. We show via numerical simulations that the
iterative algorithms we have developed converge rapidly, yielding highly
transmitting wavefronts while using relatively few measurements of the
backscatter field. Specifically, the best performing iterative algorithm yields
~70% transmission using just 15-20 measurements in the regime, where the non
iterative algorithms yield ~78.5% transmission, but require measuring the entire
modal reflection matrix. Our theoretical analysis and rigorous numerical results
validate our prediction that phase-only modulation with a given number of spatial
modes will yield higher transmission than amplitude and phase modulation with
half as many modes.
PMID- 25121538
TI - Electromagnetic energy within coated cylinders at oblique incidence and
applications to graphene coatings.
AB - We address electromagnetic (EM) wave scattering by an infinite coated cylinder at
an arbitrary incidence angle. The time-averaged EM energy stored inside the core
shell cylinder is analytically calculated for TM- and TE-polarized incident plane
waves. An analytical expression relating the internal energy to the absorption
cross section is derived. As an application, the EM energy inside dielectric
cylinders coated with isotropic graphene layers epitaxially grown on silicon
carbide (SiC) is studied. We find that off-resonance field enhancement occurs in
graphene SiC microshells for TM-polarized terahertz waves, a phenomenon that can
be explained in terms of Fano resonances.
PMID- 25121537
TI - Wavefront reconstruction in phase-shifting interferometry via sparse coding of
amplitude and absolute phase.
AB - Phase-shifting interferometry is a coherent optical method that combines high
accuracy with high measurement speeds. This technique is therefore desirable in
many applications such as the efficient industrial quality inspection process.
However, despite its advantageous properties, the inference of the object
amplitude and the phase, herein termed wavefront reconstruction, is not a trivial
task owing to the Poissonian noise associated with the measurement process and to
the 2pi phase periodicity of the observation mechanism. In this paper, we
formulate the wavefront reconstruction as an inverse problem, where the amplitude
and the absolute phase are assumed to admit sparse linear representations in
suitable sparsifying transforms (dictionaries). Sparse modeling is a form of
regularization of inverse problems which, in the case of the absolute phase, is
not available to the conventional wavefront reconstruction techniques, as only
interferometric phase modulo-2pi is considered therein. The developed sparse
modeling of the absolute phase solves two different problems: accuracy of the
interferometric (wrapped) phase reconstruction and simultaneous phase unwrapping.
Based on this rationale, we introduce the sparse phase and amplitude
reconstruction (SPAR) algorithm. SPAR takes into full consideration the
Poissonian (photon counting) measurements and uses the data-adaptive block
matching 3D (BM3D) frames as a sparse representation for the amplitude and for
the absolute phase. SPAR effectiveness is documented by comparing its performance
with that of competitors in a series of experiments.
PMID- 25121539
TI - Fast high-order perturbation of surfaces methods for simulation of multilayer
plasmonic devices and metamaterials.
AB - The scattering of time-harmonic linear waves by periodic media arises in a wide
array of applications from materials science and nondestructive testing to remote
sensing and oceanography. In this work we have in mind applications in optics,
more specifically plasmonics, and the surface plasmon polaritons that are at the
heart of remarkable phenomena such as extraordinary optical transmission, surface
enhanced Raman scattering, and surface plasmon resonance biosensing. In this
paper we develop robust, highly accurate, and extremely rapid numerical solvers
for approximating solutions to grating scattering problems in the frequency
regime where these are commonly used. For piecewise-constant dielectric
constants, which are commonplace in these applications, surface formulations are
clearly advantaged as they posit unknowns supported solely at the material
interfaces. The algorithms we develop here are high-order perturbation of
surfaces methods and generalize previous approaches to take advantage of the fact
that these algorithms can be significantly accelerated when some or all of the
interfaces are trivial (flat). More specifically, for configurations with one
nontrivial interface (and one trivial interface) we describe an algorithm that
has the same computational complexity as a two-layer solver. With numerical
simulations and comparisons with experimental data, we demonstrate the speed,
accuracy, and applicability of our new algorithms.
PMID- 25121540
TI - Numerical solution of nonparaxial scalar diffraction integrals for focused
fields.
AB - In this paper, we present sampling conditions for fast-Fourier-transform-based
field propagations. The input field and the propagation kernel are analyzed in a
combined manner to derive sampling criteria that guarantee accurate calculation
results in the output plane. These sampling criteria are also applicable to the
propagation of general fields. For focal field calculations, geometrical optics
is used to obtain a priori knowledge about the input and output fields. This a
priori knowledge is used to determine an optimum balance between computational
load and calculation accuracy. In a numerical example, correct results are
obtained even though both the input field and the propagation kernel are sampled
below the Nyquist rate. Finally, we show how chirp z-transform-based zoom
algorithms may be analyzed using the same techniques.
PMID- 25121541
TI - Large aperture adaptive doublet polymer lens for imaging applications.
AB - We report a full design process-finite element modeling, fabrication, and
characterization-of adaptive doublet polymer lenses. A first-order model was
developed and used to design fluidic doublets, analogous to their glass
counterparts. Two constant-volume fluidic chambers were enclosed by three
flexible membranes, resulting in a variable focal length doublet with a clear
aperture of 19.0 mm. Chromatic focal shift was then used to compare numerical
modeling to experimentally measured results over a positive focal length range of
55-200 mm (f/2.89 to f/10.5).
PMID- 25121542
TI - Compensation of modeling errors due to unknown domain boundary in diffuse optical
tomography.
AB - Diffuse optical tomography is a highly unstable problem with respect to modeling
and measurement errors. During clinical measurements, the body shape is not
always known, and an approximate model domain has to be employed. The use of an
incorrect model domain can, however, lead to significant artifacts in the
reconstructed images. Recently, the Bayesian approximation error theory has been
proposed to handle model-based errors. In this work, the feasibility of the
Bayesian approximation error approach to compensate for modeling errors due to
unknown body shape is investigated. The approach is tested with simulations. The
results show that the Bayesian approximation error method can be used to reduce
artifacts in reconstructed images due to unknown domain shape.
PMID- 25121543
TI - Plasmonic corrugated cylinder-cone terahertz probe.
AB - The spoof surface plasmon polariton (SPP) effect on the electromagnetic field
distribution near the tip of a periodically corrugated metal cylinder-cone probe
working at the terahertz regime was studied. We found that radially polarized
terahertz radiation could be coupled effectively through a spoof SPP into a
surface wave and propagated along the corrugated surface, resulting in more than
20* electric field enhancement near the tip of probe. Multiple resonances caused
by the antenna effect were discussed in detail by finite element computation and
theoretical analysis of dispersion relation for spoof SPP modes. Moreover, the
key figures of merit such as the resonance frequency of the SPP can be flexibly
tuned by modifying the geometry of the probe structure, making it attractive for
application in an apertureless background-free terahertz near-field microscope.
PMID- 25121544
TI - Isochromatic lines as extension of Helmholtz reciprocity principle for effect
paints.
AB - Flake-based parameters were recently introduced as a physical concept to predict
a series of measurement geometries producing similar reflection data for effect
paints. We derive expressions to calculate these so-called isochromatic lines,
connecting the two Helmholtz-reciprocal in-plane geometries with a series of out
of-plane geometries. Thus isochromatic lines can be regarded as an extension of
the Helmholtz reciprocity principle, which is valid for effect paints. We
experimentally studied seven effect paint samples with large angular color
variation along the length of four isochromatic lines. A change in illumination
angles by up to 75 degrees while following isochromatic lines led to a standard
deviation in color parameters of less than two units. When isochromatic lines
were not followed, these colorimetric parameters varied by more than 10 units
already by change in detection angle of 10 degrees . Therefore the concept of
isochromatic lines works well for effect paints.
PMID- 25121545
TI - Introducing the concept of anisotropy at different scales for modeling optical
turbulence.
AB - In this paper, the concept of anisotropy at different atmospheric turbulence
scales is introduced. A power spectrum and its associated structure function with
inner and outer scale effects and anisotropy are also shown. The power spectrum
includes an effective anisotropic parameter zeta(eff) to describe anisotropy,
which is useful for modeling optical turbulence when a non-Kolmogorov power law
and anisotropy along the direction of propagation are present.
PMID- 25121546
TI - DLAB: a class of daylight-based uniform color space.
AB - CIELAB is based on the CIE 1931 color matching functions. If we are given a new
set of color matching functions, how do we define a CIELAB-like uniform color
space for the new functions? This problem arises because the CIE recommended its
physiological cone fundamentals in 2006 and is considering a new set of color
matching functions based on them. In fact, the same problem exists for many
practical applications in digital imaging. Typical solutions involve using
illuminant-dependent color correction matrices to transform the device-dependent
color space into the CIE XYZ color space. This conversion process suffers
information loss unless the two sets of color matching functions are linear
combinations of each other. In this paper, we propose a design process that
allows us to develop a CIELAB-like color space using the native sensor
fundamentals. The basic idea is to choose the daylight locus as the yellow-blue
opponent color process. We call this class of color space DLAB. We describe the
design procedures and compare the resulting Munsell color uniformity under CIELAB
(L*, a*, b*) and DLAB (L(+) ,a(+), b(+)).
PMID- 25121547
TI - Fast reconstruction of fluorescence molecular tomography via a permissible region
extraction strategy.
AB - In order to obtain precise reconstruction results in fluorescence molecular
tomography (FMT), large-scale matrix equations would be solved in the inverse
problem generally. Thus, much time and memory needs to be consumed. In this
paper, a permissible region extraction strategy is proposed to solve this
problem. First, a preliminary result is rapidly reconstructed using the weight
matrix compressed by principal component analysis or uniform sampling. And then
the reconstructed target area in this preliminary result is considered as the a
priori permissible region to guide the final reconstruction. Phantom experiments
with double fluorescent targets are performed to test the performance of the
strategy. The results illustrate that the proposed strategy can significantly
accelerate the image reconstruction in FMT almost without quality degradation.
PMID- 25121548
TI - Asymmetric information hiding and noise-free recovery based on rotating analyzer
ellipsometry and quick-response code.
AB - We report an asymmetric optical information hiding method based on a rotating
analyzer ellipsometry technique. This asymmetric hiding architecture not only
avoids the interception of keys during transmission or distribution but also
makes the cyphertext more inconspicuous for attackers. A new kind of one-way
optical trapdoor function is constructed based on the fact that the state of
polarization (SOP) of elliptical polarized light cannot be recovered with only
the knowledge of intensity captured after passing through a linear polarizer.
Meanwhile, the SOP of a polarization ellipse could be calculated by rotating the
polarizer to record two scenes of intensity after it. Introduction of a quick
response code as a container leads to noise-free recovery for original
information and enhances practicality of the proposed cryptosystem with versatile
key sensitivity and fault tolerance capability. Numerical simulation results that
support theoretical analysis are presented. Analysis on the relationship between
hiding effect or quality of decryption and parameters of the algorithm also is
provided.
PMID- 25121551
TI - Diagnostic and prognostic TERT promoter mutations in thyroid fine-needle
aspiration biopsy.
AB - Two promoter mutations, chr5:1 295 228C>T and chr5:1 295 250C>T, in the gene for
telomerase reverse transcriptase (TERT) have been recently identified in thyroid
cancers and shown to be important in thyroid tumor pathogenesis. The diagnostic
and prognostic potentials of testing for these mutations on thyroid fine-needle
aspiration biopsy (FNAB) have not been investigated. Herein, we examined the two
TERT promoter mutations along with the BRAF V600E mutation by direct DNA
sequencing on 308 FNAB specimens preoperatively obtained from thyroid nodules
with postoperatively confirmed pathological diagnoses. We found TERT promoter
mutations in 0.0% (0/179) of benign thyroid nodules and 7.0% (9/129) of thyroid
nodules of differentiated thyroid cancer, representing a 100% diagnostic
specificity and 7.0% sensitivity, with the latter rising to 38.0% (49/129) when
combined with BRAF V600E testing. Several TERT-promoter-mutation-positive thyroid
nodules were cytologically indeterminate on FNAB. Approximately 80% of the TERT
promoter mutation-positive thyroid nodules were thyroid cancers with aggressive
clinicopathological behaviors, such as extrathyroidal invasion, lymph node
metastases, distant metastases, disease recurrence or patient death. Thus, a
positive TERT promoter mutation test not only definitively diagnoses a thyroid
nodule as cancerous but also preoperatively identifies a cancer with aggressive
potential. This is the first study, to our knowledge, of TERT promoter mutations
on thyroid FNAB, demonstrating the value of this novel molecular testing in the
diagnosis of thyroid nodules and preoperative risk stratification of thyroid
cancer. Thus, testing of TERT promoter mutations on FNAB will enhance and improve
the current molecular-based approaches to the management of thyroid nodules and
thyroid cancer.
PMID- 25121550
TI - Metagenomic identification of novel enteric viruses in urban wild rats and genome
characterization of a group A rotavirus.
AB - Rats are known as reservoirs and vectors for several zoonotic pathogens. However,
information on the viruses shed by urban wild rats that could pose a zoonotic
risk to human health is scare. Here, intestinal contents from 20 wild Norway rats
(Rattus norvegicus) collected in the city of Berlin, Germany, were subjected to
metagenomic analysis of viral nucleic acids. The determined faecal viromes of
rats consisted of a variety of known and unknown viruses, and were highly
variable among the individuals. Members of the families Parvoviridae and
Picobirnaviridae represented the most abundant species. Novel picornaviruses,
bocaviruses, sapoviruses and stool-associated circular ssDNA viruses were
identified, which showed only low sequence identity to known representatives of
the corresponding taxa. In addition, noroviruses and rotaviruses were detected as
potential zoonotic gastroenteritis viruses. However, partial-genome sequence
analyses indicated that the norovirus was closely related to the recently
identified rat norovirus and the rotavirus B was closely related to the rat
rotavirus strain IDIR; both viruses clustered separately from respective human
virus strains in phylogenetic trees. In contrast, the rotavirus A sequences
showed high identity to human and animal strains. Analysis of the nearly complete
genome of this virus revealed the known genotypes G3, P[3] and N2 for three of
the genome segments, whereas the remaining eight genome segments represented the
novel genotypes I20-R11-C11-M10-A22-T14-E18-H13. Our results indicated a high
heterogeneity of enteric viruses present in urban wild rats; their ability to be
transmitted to humans remains to be assessed in the future.
PMID- 25121549
TI - Novel porcine-like human G26P[19] rotavirus identified in hospitalized paediatric
diarrhoea patients in Ho Chi Minh City, Vietnam.
AB - During a hospital-based diarrhoeal disease study conducted in Ho Chi Minh City,
Vietnam from 2009 to 2010, we identified four symptomatic children infected with
G26P[19] rotavirus (RV)--an atypical variant that has not previously been
reported in human gastroenteritis. To determine the genetic structure and
investigate the origin of this G26P[19] strain, the whole genome of a
representative example was characterized, revealing a novel genome constellation:
G26-P[19]-I5-R1-C1-M1-A8-N1-T1-E1-H1. The genome segments were most closely
related to porcine (VP7, VP4, VP6 and NSP1) and Wa-like porcine RVs (VP1-3 and
NSP2-5). We proposed that this G26P[19] strain was the product of zoonotic
transmission coupled with one or more reassortment events occurring in human
and/or animal reservoirs. The identification of such strains has potential
implications for vaccine efficacy in south-east Asia, and outlines the utility of
whole-genome sequencing for studying RV diversity and zoonotic potential during
disease surveillance.
PMID- 25121553
TI - Two human challenge studies confirm high infectivity of Norwalk virus.
PMID- 25121554
TI - Yeast as a potential vehicle for neglected tropical disease drug discovery.
AB - High-throughput screening (HTS) efforts for neglected tropical disease (NTD) drug
discovery have recently received increased attention because several initiatives
have begun to attempt to reduce the deficit in new and clinically acceptable
therapies for this spectrum of infectious diseases. HTS primarily uses two basic
approaches, cell-based and in vitro target-directed screening. Both of these
approaches have problems; for example, cell-based screening does not reveal the
target or targets that are hit, whereas in vitro methodologies lack a cellular
context. Furthermore, both can be technically challenging, expensive, and
difficult to miniaturize for ultra-HTS [(u)HTS]. The application of yeast-based
systems may overcome some of these problems and offer a cost-effective platform
for target-directed screening within a eukaryotic cell context. Here, we review
the advantages and limitations of the technologies that may be used in yeast cell
based, target-directed screening protocols, and we discuss how these are
beginning to be used in NTD drug discovery.
PMID- 25121552
TI - Enalapril and ASS inhibit tumor growth in a transgenic mouse model of islet cell
tumors.
AB - Accumulating evidence suggests a role for angiotensin-converting enzymes
involving the angiotensin II-receptor 1 (AT1-R) and the cyclooxygenase pathway in
carcinogenesis. The effects of ASS and enalapril were assessed in vitro and in a
transgenic mouse model of pancreatic neuroendocrine neoplasms (pNENs). The
effects of enalapril and ASS on proliferation and expression of the AGTR1A and
its target gene vascular endothelial growth factor (Vegfa) were assessed in the
neuroendocrine cell line BON1. Rip1-Tag2 mice were treated daily with either 0.6
mg/kg bodyweight of enalapril i.p., 20 mg/kg bodyweight of ASS i.p., or a vehicle
in a prevention (weeks 5-12) and a survival group (week 5 till death). Tumor
surface, weight of pancreatic glands, immunostaining for AT1-R and nuclear factor
kappa beta (NFKB), and mice survival were analyzed. In addition, sections from
human specimens of 20 insulinomas, ten gastrinomas, and 12 non-functional pNENs
were evaluated for AT1-R and NFKB (NFKB1) expression and grouped according to the
current WHO classification. Proliferation was significantly inhibited by
enalapril and ASS in BON1 cells, with the combination being the most effective.
Treatment with enalapril and ASS led to significant downregulation of known
target genes Vegf and Rela at RNA level. Tumor growth was significantly inhibited
by enalapril and ASS in the prevention group displayed by a reduction of tumor
size (84%/67%) and number (30%/45%). Furthermore, daily treatment with enalapril
and ASS prolonged the overall median survival compared with vehicle-treated Rip1
Tag2 (107 days) mice by 9 and 17 days (P=0.016 and P=0.013). The AT1-R and the
inflammatory transcription factor NFKB were abolished completely upon enalapril
and ASS treatment. AT1-R and NFKB expressions were observed in 80% of human
pNENs. Enalapril and ASS may provide an approach for chemoprevention and
treatment of pNENs.
PMID- 25121555
TI - Discovery of new uncompetitive inhibitors of glucose-6-phosphate dehydrogenase.
AB - The enzyme glucose-6-phosphate dehydrogenase (G6PDH) catalyzes the first step of
the oxidative branch of the pentose phosphate pathway, which provides cells with
NADPH, an essential cofactor for many biosynthetic pathways and antioxidizing
enzymes. In Trypanosoma cruzi, the G6PDH has being pursued as a relevant target
for the development of new drugs against Chagas disease. At present, the best
characterized inhibitors of T. cruzi G6PDH are steroidal halogenated compounds
derivatives from the mammalian hormone precursor dehydroepiandrosterone, which
indeed are also good inhibitors of the human homologue enzyme. The lack of target
selectivity might result in hemolytic side effects due to partial inhibition of
human G6PDH in red blood cells. Moreover, the treatment of Chagas patients with
steroidal drugs might also cause undesired androgenic side effects. Aiming to
identify of new chemical classes of T. cruzi G6PDH inhibitors, we performed a
target-based high-throughput screen campaign against a commercial library of
diverse compounds. Novel TcG6PDH inhibitors were identified among
thienopyrimidine and quinazolinone derivatives. Preliminary structure activity
relationships for the identified hits are presented, including structural
features that contribute for selectivity toward the parasite enzyme. Our results
indicate that quinazolinones are promising hits that should be considered for
further optimization.
PMID- 25121556
TI - A CXCR1 haplotype hampers HIV-1 matrix protein p17 biological activity.
AB - OBJECTIVE: Monocyte inflammatory processes are fundamental events in AIDS
pathogenesis. HIV-1 matrix protein p17, released from infected cells, was found
to exert an interleukin (IL)-8 chemokine-like activity on human monocytes,
promoting their trafficking and sustaining inflammatory processes, after binding
to CXCR1. A haplotype of the CXCR1 gene (CXCR1_300_142) has been associated with
slow HIV disease progression. Here, we determine how CXCR1 genetic variations
impact on p17 biological activity. DESIGN/METHODS/RESULTS: Our results show that
Jurkat cells overexpressing CXCR1 or the receptor carrying single polymorphism
CXCR1_300 or CXCR1_142 are able to adhere and migrate in response to both IL-8
and p17. On the contrary, Jurkat cells overexpressing CXCR1_300_142 and monocytes
of individuals with such CXCR1 polymorphisms lose the capacity to adhere and
migrate in response to p17, but not to their physiological ligand IL-8. Surface
plasmon resonance (SPR) and multispectral imaging flow cytometry showed that p17
bound with similar affinity to CXCR1 and CXCR1_300_142. Moreover, whereas p17 was
able to activate CXCR1, it was incapable of functionally interacting with
CXCR1_300_142 by phosphorylating extracellular signal-regulated kinase 1/2, which
regulates chemokine-induced cellular responses. Finally, mutagenesis studies
showed that, unlike IL-8, p17 does not use Glu-Leu-Arg-like motifs to activate
CXCR1. CONCLUSIONS: Our results, showing the inability of p17 to activate
CXCR1_300_142, a receptor found to be expressed on immune cells of patients with
a low progression of HIV disease, point to a crucial role of p17 in AIDS
pathogenesis. Our findings herein call for an exploration of the therapeutic
potential of blocking the p17/CXCR1 axis in HIV infection.
PMID- 25121558
TI - Erratum to: Effects of Saccharomyces boulardii on Neonatal Hyperbilirubinemia: A
Randomized Controlled Trial.
PMID- 25121557
TI - Hydrogen preconditioning during ex vivo lung perfusion improves the quality of
lung grafts in rats.
AB - BACKGROUND: Although the benefits of ex vivo lung perfusion (EVLP) have been
globally advocated, the potentially deleterious effects of applying EVLP, in
particular activation of proinflammatory cascades and alteration of metabolic
profiles, are rarely discussed. This study examined proinflammatory events and
metabolic profiles in lung grafts on EVLP and tested whether preconditioning lung
grafts with inhaled hydrogen, a potent, cytoprotective gaseous signaling
molecule, would alter the lungs' response to EVLP. METHODS: Rat heart-lung blocks
were mounted on an acellular normothermic EVLP system for 4 hr and ventilated
with air or air supplemented with 2% hydrogen. Arterial and airway pressures were
monitored continuously; perfusate was sampled hourly to examine oxygenation.
After EVLP, the lung grafts were transplanted orthotopically into syngeneic rats,
and lung function was examined. RESULTS: Placing lung grafts on EVLP resulted in
significant upregulation of the messenger RNAs for several proinflammatory
cytokines, higher glucose consumption, and increased lactate production. Hydrogen
administration attenuated proinflammatory changes during EVLP through
upregulation of the heme oxygenase-1. Hydrogen administration also promoted
mitochondrial biogenesis and significantly decreased lactate production.
Additionally, in the hydrogen-treated lungs, the expression of hypoxia-inducible
factor-1 was significantly attenuated during EVLP. These effects were maintained
throughout EVLP and led to better posttransplant lung graft function in the
recipients of hydrogen-treated lungs. CONCLUSIONS: Lung grafts on EVLP exhibited
prominent proinflammatory changes and compromised metabolic profiles.
Preconditioning lung grafts using inhaled hydrogen attenuated these
proinflammatory changes, promoted mitochondrial biogenesis in the lungs
throughout the procedure, and resulted in better posttransplant graft function.
PMID- 25121559
TI - Stewart-Bluefarb syndrome: Report of five cases and a review of literature.
AB - Stewart-Bluefarb syndrome is a rare angioproliferative disorder characterised by
acroangiodermatitis associated with an underlying arteriovenous shunt. This
condition should be differentiated from acroangiodermatitis of Mali classically
described in association with chronic venous insufficiency. Patients with Stewart
Bluefarb syndrome typically present with lower leg pigmented macules, papules and
plaques that can coalesce to form larger confluent patches of pigmentation.
Recognition of Stewart-Bluefarb syndrome may be difficult or delayed as the
cutaneous manifestations may resemble a variety of other dermatological
conditions. Most commonly, acroangiodermatitis may be confused with Kaposi's
sarcoma and the condition is often referred to as 'Pseudo-Kaposi's sarcoma'.
Acroangiodermatitis may also resemble or coexist with pigmentation of chronic
venous insufficiency. As seen in this report, acroangiodermatitis may also be
clinically confused with the 'cavernous' form of a capillary malformation. Here,
we describe five patients with Stewart-Bluefarb syndrome. In one female and two
male patients the diagnosis was delayed as the acroangiodermatitis closely
resembled other conditions. All underlying arterio-venous communications were
initially diagnosed on duplex ultrasound and confirmed with magnetic resonance
angiography. Four patients were found to have a congenital arterio-venous
malformation while one was diagnosed with a post-thrombotic arterio-venous
fistula. Management included observation and intervention using a variety of
techniques including percutaneous or trans-catheter embolisation, endovenous
laser, radiofrequency ablation and foam ultrasound guided sclerotherapy. This
case series highlights the challenges involved in the diagnosis and management of
Stewart-Bluefarb syndrome. Given the local and systemic sequelae of high flow
shunts, correct diagnosis and early detection of the underlying arterio-venous
abnormality is crucial in the long-term management of these patients and in
preventing the associated complications.
PMID- 25121560
TI - Regional differences in statistical geometry of endothelial dense granules in
human extremity veins.
AB - OBJECTIVES: Leg and arm human veins are exposed to different gravitational
stresses. We investigated if there is difference in the amount and geometry of
secretory vesicles in their endothelium. METHODS: Superficial small vein segments
were removed during vascular operations for electromicroscopic analysis.
Vesicular area/total endothelial cross-sectional area was determined by computer
based morphometry. Long and short axes of granule cross sections were measured by
image analyzing software. RESULTS: Vesicular density in all samples was 2.26 +/-
0.34%. There was no significant difference between the vesicular densities of
upper extremity and leg. The shape of the vesicles was more frequently elongated
in leg than in arm sections (p < 0.01). CONCLUSIONS: The density of the vesicles
does not depend on vascular region or orthostatic load. Ellipticity of these
granules is significantly different in areas exposed to different gravitational
stresses. This might contribute to the differences of thrombotic and hemodynamic
properties of leg and upper body veins.
PMID- 25121561
TI - Urate oxidase for the prevention and treatment of tumour lysis syndrome in
children with cancer.
AB - BACKGROUND: Tumour lysis syndrome (TLS) is a serious complication of malignancies
and can result in renal failure or death. Preliminary reports suggest that urate
oxidase is effective in reducing serum uric acid, the build-up of which causes
TLS. It is uncertain whether high-quality evidence exists to support its routine
use in children with malignancies. OBJECTIVES: To assess the effects and safety
of urate oxidase for the prevention and treatment of TLS in children with
malignancies. SEARCH METHODS: This is an update of the original review. We
performed a comprehensive search of the Cochrane Central Register of Controlled
Trials (CENTRAL) (in The Cochrane Library issue 1, 2013), MEDLINE (1966 to
February 2013), Embase (1980 to February 2013), and CINAHL (1982 to February
2013). In addition, we searched the reference lists of all identified relevant
papers. We also explored other internet sources (updated search on 26 February
2013): the NHS' National Research Register, the US National Institutes of Health
Ongoing Trials Register, the metaRegister of Controlled Trials, and ProQuest
Dissertations & Theses Database. We also screened conference proceedings of the
American Society of Clinical Oncology, the European Society for Medical Oncology,
and the International Society of Paediatric Oncology meetings from 1993 to 2012.
Finally, we contacted experts in the field and the manufacturer of rasburicase,
Sanofi-aventis. SELECTION CRITERIA: Randomised controlled trials (RCT) and
controlled clinical trials (CCT) of urate oxidase for the prevention or treatment
of TLS in children under 18 years with any malignancy. DATA COLLECTION AND
ANALYSIS: Two review authors independently extracted trial data and assessed
individual trial quality. We used risk ratios (RR) for dichotomous data and mean
difference (MD) for continuous data. MAIN RESULTS: We included seven trials,
involving 471 participants in the treatment groups and 603 participants in the
control groups. One RCT and five CCTs compared urate oxidase and allopurinol.
Three trials tested Uricozyme, and three trials tested rasburicase for the
prevention of TLS.The RCT showed no significant difference in mortality (both all
cause mortality and mortality due to TLS), renal failure, and adverse effects
between the treatment and the control groups. The frequency of normalisation of
uric acid at four hours (Fisher's exact test P < 0.001) and area under curve of
uric acid at four days (MD -201.00 mg/dLhr, 95% confidence interval (CI) -258.05
mg/dLhr to -143.95 mg/dLhr; P < 0.00001) were significantly better in the
treatment group. The trial did not evaluate the primary outcome (incidence of
clinical TLS).Pooled results of three CCTs showed significantly lower mortality
due to TLS in the treatment group (RR 0.05, 95% CI 0.00 to 0.89; P = 0.04); all
cause mortality was not significantly different between the groups. Pooled
results from five CCTs showed significantly lower incidence of renal failure in
the treatment group (RR 0.26, 95% CI 0.08 to 0.89; P = 0.03). Results of CCTs
also showed significantly lower uric acid in the treatment group at two days
(three CCTs), three days (two CCTs), four days (two CCTs), and seven days (one
CCT) after therapy, but not one day (three CCTs), five days (one CCT), and 12
days (one CCT) after therapy. Pooled results from three CCTs showed higher
frequency of adverse effects in participants who received urate oxidase (RR 9.10,
95% CI 1.29 to 64.00; P = 0.03). One CCT evaluated the primary outcome; no
significant difference was identified.Another included RCT, with 30 participants,
compared different doses of rasburicase (0.2 mg/kg versus 0.15 mg/kg), which
demonstrated no significant difference in uric acid normalisation and uric acid
level at four hours). Common adverse events of urate oxidase included
hypersensitivity, haemolysis, and anaemia, but no significant difference between
treatment groups was identified. No significant difference in mortality (all
cause mortality and mortality due to TLS) and renal failure was identified. The
primary outcome was not evaluated.All included trials were highly susceptible to
biases. AUTHORS' CONCLUSIONS: Although urate oxidase might be effective in
reducing serum uric acid, it is unclear whether it reduces clinical tumour lysis
syndrome, renal failure, or mortality. Adverse effects might be more common for
urate oxidase compared with allopurinol. Clinicians should weigh the potential
benefits of reducing uric acid and uncertain benefits of preventing mortality or
renal failure from TLS against the potential risk of adverse effects.
PMID- 25121562
TI - Predictors of postpartum depression.
AB - OBJECTIVE: To examine sociodemographic factors, pregnancy-associated psychosocial
stress and depression, health risk behaviors, prepregnancy medical and
psychiatric illness, pregnancy-related illnesses, and birth outcomes as risk
factors for post-partum depression (PPD). METHODS: A prospective cohort study
screened women at 4 and 8 months of pregnancy and used hierarchical logistic
regression analyses to examine predictors of PPD. The study sample include 1,423
pregnant women at a university-based high risk obstetrics clinic. A score of >=10
on the Patient Health Questionnaire-9 (PHQ-9) indicated clinically significant
depressive symptoms. RESULTS: Compared with women without significant postpartum
depressive symptoms, women with PPD were significantly younger (p<0.0001), more
likely to be unemployed (p=0.04), had more pregnancy associated depressive
symptoms (p<0.0001) and psychosocial stress (p<0.0001), were more likely to be
smokers (p<0.0001), were more likely to be taking antidepressants (ADs) during
pregnancy (p=0.002), were less likely to drink any alcohol during pregnancy
(p=0.02), and were more likely to have prepregnancy medical illnesses, including
diabetes (p=0.02) and neurologic conditions (p=0.02). CONCLUSION: Specific
sociodemographic and clinical risk factors for PPD were identified that could
help physicians target depression case finding for pregnant women.
PMID- 25121563
TI - Azithromycin associated with a reduction in 90-day mortality among older
pneumonia patients, although a true clinical benefit is uncertain.
PMID- 25121564
TI - Peer review of human studies run amok: a break in the fiduciary relation between
scientists and the public.
AB - Peer review aims to ensure the quality and credibility of research reporting.
Conducted by volunteer scientists who receive no guidance or direction, peer
review widely varies from fast and facilitative, to unclear and obstructive. Poor
quality is an issue because most science research is publicly funded, whereby
scientists must make an effort to quickly disseminate their findings back to the
public. An unfortunately not uncommon barrier in this process is ineffective peer
review. Most scientists agree that when done well, editors and reviewers drive
and maintain the high standards of science. At the same time, ineffective peer
review can cause great delay with no introduced improvement in final product.
These delays and requests interfere with the path of communication between
scientist and public, at a great cost to editors, reviewers, authors and those
who stand to benefit from application of the results of the studies. We offer a
series of concrete recommendations to improve this process.
PMID- 25121565
TI - Balancing competing risks: perinatal exposure to macrolides increases the risk of
infantile hypertrophic pyloric stenosis.
PMID- 25121566
TI - Computational models on quantitative prediction of bioactivity of HIV-1 integrase
3' processing inhibitors.
AB - In this study, four computational quantitative structure-activity relationship
(QSAR) models were built to predict the bioactivity of 3' processing (3'P)
inhibitors of HIV-1 integrase. Some 453 inhibitors whose bioactivity values were
detected by the radiolabelling method were collected. The molecular structures
were represented with MOE descriptors. In total, 21 descriptors were selected for
modelling. All inhibitors were divided into a training set and a test set with
two methods: (1) by a Kohonen's self-organizing map (SOM); (2) by a random
selection. For every training set and test set, a multilinear regression (MLR)
analysis and a support vector machine (SVM) were used to establish models,
respectively. For the training/test set divided by SOM, the correlation
coefficients (r) were over 0.84, and for the training/test set split randomly,
the r values were over 0.86. Some molecular properties such as hydrogen bond
donor capacity, atomic partial charge properties, molecular refractivity, the
number of aromatic bonds and molecular surface area, volume and shape properties
played important roles for inhibiting 3' processing step of HIV-1 integrase.
PMID- 25121567
TI - Effect of unawareness on rehabilitation outcome in a randomised controlled trial
of multicomponent intervention for patients with mild Alzheimer's disease.
AB - Unawareness of deficit has been shown to affect the outcome of targeted cognitive
intervention programmes applied to patients with Alzheimer' disease (AD), but the
effects on multimodal therapeutic approaches have not yet been explored. This
research investigated the efficacy of the Multi-Intervention Programme (MIP)
approach on improving cognitive, functional, affective, and behavioural symptoms
in people with mild AD. In addition, we examined whether the presence of
unawareness influences the MIP outcomes. Sixty-one mild stage AD patients were
randomly assigned to either an experimental group which carried out an MIP
individually (48 sessions, 16 weeks duration), combining diverse cognitive tasks,
training in daily life and recreational activities, or a waiting list group which
did not receive any treatment for the same time period. The efficacy of MIP (vs.
waiting list) was tested using various standardised neuropsychological,
functional, and behavioural outcome measures. Planned analyses were carried out
to determine the effect of unawareness versus awareness on such outcomes. The
results showed that patients overall benefited from the MIP in terms of both
cognitive and non-cognitive symptoms. AD patients with awareness of deficits
showed positive effects on all outcome measures in comparison with the waiting
list group, while AD patients with unawareness showed improvements in non
cognitive symptoms only. In conclusion, the presence of unawareness reduces the
cognitive and functional effects of MIP in patients with mild AD.
PMID- 25121568
TI - A quantitative investigation of hemodynamic adaptation to pregnancy using uterine
artery Doppler ultrasonography and finger photoplethysmography.
AB - OBJECTIVE: Normal pregnancy is characterized by maternal hemodynamic adaptations
of cardiovascular system and uterine artery. We aimed to investigate
quantitatively the relationship between uterine artery Doppler (Ut AD)
ultrasonography and finger photoplethysmography (PPG) in each of the three
trimesters. METHODS: Eighty normal pregnancy subjects were recruited from the
nulliparous women with uncomplicated singleton pregnancy presenting for a routine
ultrasound scan and divided into three groups according to their trimester.
Comparative analysis were conducted between Ut AD ultrasonography and finger PPG
within and across trimesters, particularly with focus on the relationship between
Uterine Artery Resistance Index (UtA RI) and photoplethysmographic reflection
index (PPG RI) throughout pregnancy. Additional 10 preeclampsia patients in third
trimester were enrolled for comparison. RESULTS: Both UtA RI and PPG RI were
markedly decreased with gestation in normal pregnancy and generally consistent
with each other in trend. The preeclampsia patients of third trimester were
significantly higher in both indices, even more than normal pregnancy subjects of
first trimester. CONCLUSIONS: The results of this study revealed clear
relationship between UtA RI and PPG RI throughout pregnancy which could be
exploited to enhance the potential ability in early recognition of
pathophysiologic process in maternal adaptation and prediction of complicated
pregnancy.
PMID- 25121569
TI - Target temperature management for postcardiac arrest patients.
PMID- 25121571
TI - Cortical thickness in ALS: towards a marker for upper motor neuron involvement.
AB - OBJECTIVE: Examine whether cortical thinning is a disease-specific phenomenon
across the spectrum of motor neuron diseases in relation to upper motor neuron
(UMN) involvement. METHODS: 153 patients (112 amyotrophic lateral sclerosis
(ALS), 19 patients with a clinical UMN phenotype, 22 with a lower motor neuron
(LMN) phenotype), 60 healthy controls and 43 patients with an ALS mimic disorder
were included for a cross-sectional cortical thickness analysis. Thirty-nine
patients with ALS underwent a follow-up scan. T1-weighted images of the brain
were acquired using a 3 T scanner. The relation between cortical thickness and
clinical measures, and the longitudinal changes were examined. RESULTS: Cortical
thickness of the precentral gyrus (PCG) was significantly reduced in ALS
(p=1.71*10(-13)) but not in mimic disorders (p=0.37) or patients with an LMN
phenotype (p=0.37), as compared to the group of healthy controls. Compared to
patients with ALS, patients with a UMN phenotype showed an even lower PCG
cortical thickness (p=1.97*10(-3)). Bulbar scores and arm functional scores
showed a significant association with cortical thickness of corresponding body
regions of the motor homunculus. Longitudinal analysis revealed a decrease of
cortical thickness in the left temporal lobe of patients with ALS
(parahippocampal region p=0.007 and fusiform cortex p=0.001). CONCLUSIONS: PCG
cortical thinning was found to be specific for motor neuron disease with clinical
UMN involvement. Normal levels of cortical thickness in mimic disorders or LMN
phenotypes suggest that cortical thinning reflects pathological changes related
to UMN involvement. Progressive cortical thinning in the temporal lobe suggests
recruitment of non-motor areas, over time.
PMID- 25121572
TI - CSF lactate levels, tau proteins, cognitive decline: a dynamic relationship in
Alzheimer's disease.
AB - OBJECTIVES: To investigate, in patients with Alzheimer's Disease (AD), the
possible interplay linking alteration of neuronal energy metabolism, as measured
via cerebrospinal fluid (CSF) lactate concentration, to severity of AD
neurodegenerative processes and impairment of cognitive abilities. METHODS: In
this study we measured and correlated CSF lactate concentrations, AD biomarker
levels (tau-proteins and beta-amyloid) and Mini-Mental State Examination (MMSE)
score in a population of drug-naive patients with AD ranging from mild
(MMSE>=21/30) to moderate-severe (MMSE<21/30) cognitive decline. They were
compared to healthy controls and patients with vascular dementia (VaD). RESULTS:
Patients with AD (n=145) showed a significant increase of CSF lactate
concentration compared to controls (n=80) and patients with VaD (n=44), which was
higher in mild (n=67) than in patients with moderate-severe AD (n=78). Moreover,
we found, in either the whole AD population or both subgroups, a CSF profile in
which higher CSF levels of t-tau and p-tau proteins corresponded to lower
concentrations of lactate. CONCLUSIONS: We verified the occurrence of high CSF
lactate levels in patients with AD, which may be ascribed to mitochondria
impairment. Hypothesising that tau proteins may exert a detrimental effect on the
entire cellular energy metabolism, the negative correlation found between lactate
and tau-protein levels may allow speculation that tau toxicity, already
demonstrated to have affected mitochondria, could also impair glycolytic
metabolism with a less evident increase of lactate levels in more severe AD.
Thus, we suggest a dynamic relationship between neuronal energy metabolism, tau
proteins and cognitive decline in AD and propose the clinical potential of
assessing CSF lactate levels in patients with AD to better define the neuronal
brain metabolism damage.
PMID- 25121573
TI - Survey of common practices among oculofacial surgeons in the Asia-Pacific region:
Graves' orbitopathy.
AB - AIM: A web-based anonymous survey was performed to evaluate practice preferences
in the management of Graves' orbitopathy amongst oculofacial surgeons in the Asia
Pacific region. METHODS: A questionnaire with contentious topics in Graves'
orbitopathy was sent out via email to oculofacial surgeons in 14 countries within
Asia-Pacific between May to December 2012. RESULTS: A response rate of 25.2% to
34.6% was achieved (32-44 of 127 participants). 61.0% of respondents encountered
Graves' orbitopathy commonly in their practice. The more common causes of vision
loss in Graves' orbitopathy included dysthyroid optic neuropathy (67.5%) and
exposure keratopathy (15.0%). The clinical activity score was the most popular
grading system for assessing Graves' orbitopathy. The preferred non-surgical
therapeutic approaches included intravenous pulsed methylprednisolone (79.5%),
oral steroids (56.4%), orbital radiation (12.8%), steroid-sparing
immunosuppressants (10.3%) and watchful observation (7.7%). Thyroid orbital
decompression was uncommonly or rarely performed by respondents. Orbital surgical
decompression was most commonly performed via the two-wall technique (73.5%) and
most respondents performed fat decompression (69.4%). Post-operatively, the most
common complications include under correction (45.5%) and diplopia (42.4%).
CONCLUSION: We report the results of the first survey on the management of
Graves' orbitopathy amongst oculofacial surgeons in Asia-Pacific. Our respondents
practice preferences reflected the Graves' orbitopathy management consensus
statement by the European group on Graves' orbitopathy in 2008.
PMID- 25121570
TI - Clinical and neuroradiological differences of paediatric acute disseminating
encephalomyelitis with and without antibodies to the myelin oligodendrocyte
glycoprotein.
AB - BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibodies have been
recently described in children with acute disseminating encephalomyelitis (ADEM),
but the clinical and neuroradiological characterisation of this subgroup is
lacking. OBJECTIVE: To compare the clinical and neuroradiological features of
paediatric ADEM with and without MOG antibodies. METHODS: Clinical course,
cerebrospinal fluid (CSF)-, MRI studies, outcome and MOG status of 33 paediatric
ADEM prospectively studied were reviewed. RESULTS: MOG antibodies (median 1:2560;
range 1:160-1:20 480) were detected in 19 children with ADEM. The majority of
children showed a decline of serum MOG-IgG titres over time. Children with MOG
antibodies did not differ in their age at presentation, sex ratio, the presence
of oligoclonal bands, clinical symptoms or initial severity, apart from a higher
CSF cell count (p=0.038), compared with children without MOG antibodies. In
addition, further relapsing demyelinating episodes associated with MOG antibodies
were observed only in children with MOG antibodies. All 19 children with MOG
antibodies had a uniform MRI pattern, characterised by large, hazy and bilateral
lesions and the absence of atypical MRI features (eg, mainly small lesions, well
defined lesions), which was significantly different compared to that of children
without MOG antibodies (p=0.003; and p=0.032, respectively). In addition,
children with MOG antibodies had involvement of more anatomical areas (p=0.035)
including the myelon characterised by a longitudinally extensive transverse
myelitis (p=0.003), more often a complete resolution of lesions (p=0.036) and a
better outcome (p=0.038). CONCLUSIONS: Patients with ADEM with MOG antibodies in
our cohort had a uniform MRI characterised by large, bilateral and widespread
lesions with an increased frequency of longitudinal extensive transverse myelitis
and a favourable clinical outcome in contrast to children lacking MOG antibodies.
PMID- 25121574
TI - Formation of bare UO2(2+) and NUO(+) by fragmentation of gas-phase uranyl
acetonitrile complexes.
AB - In a prior study [Van Stipdonk; et al. J. Phys. Chem. A 2006, 110, 959-970],
electrospray ionization (ESI) was used to generate doubly charged complex ions
composed of the uranyl ion and acetonitrile (acn) ligands. The complexes, general
formula [UO2(acn)n](2+), n = 0-5, were isolated in an 3-D quadrupole ion-trap
mass spectrometer to probe intrinsic reactions with H2O. Two general reaction
pathways were observed: (a) the direct addition of one or more H2O ligands to the
doubly charged complexes and (b) charge-exchange reactions. For the former, the
intrinsic tendency to add H2O was dependent on the number and type of nitrile
ligand. For the latter, charge exchange involved primarily the formation of
uranyl hydroxide, [UO2OH](+), presumably via a collision with gas-phase H2O and
the elimination of a protonated nitrile ligand. Examination of general ion
fragmentation patterns by collision-induced dissociation, however, was hindered
by the pronounced tendency to generate hydrated species. In an update to this
story, we have revisited the fragmentation of uranyl-acetonitrile complexes in a
linear ion-trap (LIT) mass spectrometer. Lower partial pressures of adventitious
H2O in the LIT (compared to the 3-D ion trap used in our previous study)
minimized adduct formation and allowed access to lower uranyl coordination
numbers than previously possible. We have now been able to investigate the
fragmentation behavior of these complex ions completely, with a focus on tendency
to undergo ligand elimination versus charge reduction reactions. CID can be used
to drive ligand elimination to completion to furnish the bare uranyl dication,
UO2(2+). In addition, fragmentation of [UO2(acn)](2+) generated [UO2(NC)](+),
which subsequently fragmented to furnish NUO(+). Formation of the nitrido by
transfer of N from cyanide was confirmed using precursors labeled with (15)N. The
observed formation of [UO2(NC)](+) and NUO(+) was modeled by density functional
theory.
PMID- 25121578
TI - Evidence of water-in-ionic liquid microemulsion formation by nonionic surfactant
Brij-35.
AB - Brij-35, a common and popular nonionic surfactant, is shown to form water-in
ionic liquid (w/IL) microemulsions with IL 1-butyl-3-methylimidazolium
hexafluorophosphate ([bmim][PF6]) as the bulk phase. The presence of
w/[bmim][PF6] microemulsions is hinted by the significantly increased solubility
of water in Brij-35 solution of [bmim][PF6]. The formation of w/[bmim][PF6]
microemulsions by Brij-35 is confirmed using dynamic light scattering (DLS) and
small-angle X-ray scattering (SAXS) measurements. Brij-35 forms reverse micelle
type aggregates within [bmim][PF6] in the absence of added-water. These reverse
micelles become w/[bmim][PF6] microemulsions as the water is added to the system.
As the water loading (w0) is increased, the average diameter of the aggregates
increases. Fourier transform infrared (FTIR) absorbance data reveal the presence
of both "bound" and "free" water within the system. The "bound" water is
associated with the water pools of the w/[bmim][PF6] microemulsions. Excited
state proton transfer (ESPT) involving probe pyranine shows deprotonation of
pyranine within the water pools of the w/[bmim][PF6] microemulsions.
PMID- 25121576
TI - Photochemical tyrosine oxidation in the structurally well-defined alpha3Y
protein: proton-coupled electron transfer and a long-lived tyrosine radical.
AB - Tyrosine oxidation-reduction involves proton-coupled electron transfer (PCET) and
a reactive radical state. These properties are effectively controlled in enzymes
that use tyrosine as a high-potential, one-electron redox cofactor. The alpha3Y
model protein contains Y32, which can be reversibly oxidized and reduced in
voltammetry measurements. Structural and kinetic properties of alpha3Y are
presented. A solution NMR structural analysis reveals that Y32 is the most deeply
buried residue in alpha3Y. Time-resolved spectroscopy using a soluble flash
quench generated [Ru(2,2'-bipyridine)3](3+) oxidant provides high-quality Y32-O*
absorption spectra. The rate constant of Y32 oxidation (kPCET) is pH dependent:
1.4 * 10(4) M(-1) s(-1) (pH 5.5), 1.8 * 10(5) M(-1) s(-1) (pH 8.5), 5.4 * 10(3)
M(-1) s(-1) (pD 5.5), and 4.0 * 10(4) M(-1) s(-1) (pD 8.5). k(H)/k(D) of Y32
oxidation is 2.5 +/- 0.5 and 4.5 +/- 0.9 at pH(D) 5.5 and 8.5, respectively.
These pH and isotope characteristics suggest a concerted or stepwise, proton
first Y32 oxidation mechanism. The photochemical yield of Y32-O* is 28-58% versus
the concentration of [Ru(2,2'-bipyridine)3](3+). Y32-O* decays slowly, t1/2 in
the range of 2-10 s, at both pH 5.5 and 8.5, via radical-radical dimerization as
shown by second-order kinetics and fluorescence data. The high stability of Y32
O* is discussed relative to the structural properties of the Y32 site. Finally,
the static alpha3Y NMR structure cannot explain (i) how the phenolic proton
released upon oxidation is removed or (ii) how two Y32-O* come together to form
dityrosine. These observations suggest that the dynamic properties of the protein
ensemble may play an essential role in controlling the PCET and radical decay
characteristics of alpha3Y.
PMID- 25121579
TI - Palladium-catalyzed intramolecular oxidative coupling involving double C(sp(2))-H
bonds for the synthesis of annulated biaryl sultams.
AB - The palladium-catalyzed intramolecular oxidative coupling described herein
involves a double C(sp(2))-H bond functionalization in sulfonanilides, providing
a workable access to biaryl sultams annulated into a six-membered ring that are
otherwise difficult to obtain by literature methods. The other synthetic
applications of this protocol including the synthesis of biaryl sultams
containing a seven-membered ring and analogous sultones are also presented.
PMID- 25121577
TI - Reduction-sensitive dual functional nanomicelles for improved delivery of
paclitaxel.
AB - We have developed a dual-functional nanocarrier composed of a hydrophilic
polyethylene glycol (PEG) and a hydrophobic farnesylthiosalicylate (FTS, a
nontoxic Ras antagonist), which is effective in delivery of hydrophobic
anticancer drug, paclitaxel (PTX). To facilitate the retention of the therapeutic
activity of the carrier, FTS was coupled to PEG via a reduction-sensitive
disulfide linkage (PEG5k-S-S-FTS2). PEG5k-S-S-FTS2 conjugate formed uniform
micelles with very small size (~30 nm) and the hydrophobic drug PTX could be
readily incorporated into the micelles. Interestingly, inclusion of a disulfide
linkage into the PEG5k-FTS2 micellar system resulted in a 4-fold decrease in the
critical micelle concentration (CMC). In addition, the PTX loading capacity and
colloidal stability of PTX-loaded micelles were improved. HPLC-MS showed that
parent FTS could be more effectively released from PEG5k-S-S-FTS2 conjugate in
tumor cells/tissues compared to PEG5k-FTS2 conjugate in vitro and in vivo. PEG5k
S-S-FTS2 exhibited a higher level of cytotoxicity toward tumor cells than PEG5k
FTS2 without a disulfide linkage. Furthermore, PTX-loaded PEG5k-S-S-FTS2 micelles
were more effective in inhibiting the proliferation of cultured tumor cells
compared to Taxol and PTX loaded in PEG5k-FTS2 micelles. More importantly, PTX
loaded PEG5k-S-S-FTS2 micelles demonstrated superior antitumor activity compared
to Taxol and PTX formulated in PEG5k-FTS2 micelles in an aggressive murine breast
cancer model (4T1.2).
PMID- 25121580
TI - Loop-Closure and Gaussian Models of Collective Structural Characteristics of
Capped PEO Oligomers in Water.
AB - Parallel-tempering MD results for a CH3(CH2-O-CH2)mCH3 chain in water are
exploited as a database for analysis of collective structural characteristics of
the PEO globule with a goal of defining models permitting statistical
thermodynamic analysis of dispersants of Corexit type. The chain structure
factor, relevant to neutron scattering from a deuterated chain in null water, is
considered specifically. The traditional continuum-Gaussian structure factor is
inconsistent with the simple k -> infinity behavior, but we consider a discrete
Gaussian model that does achieve that consistency. Shifting and scaling the
discrete-Gaussian model helps to identify the low-k to high-k transition near k ~
2pi/0.6 nm when an empirically matched number of Gaussian links is about one
third of the total number of effective atom sites. This short distance-scale
boundary of 0.6 nm is directly verified with the r space distributions, and this
distance is thus identified with a natural size for coarsened monomers. The
probability distribution of Rg(2) is compared with the classic predictions for
both the Gaussian model and freely jointed chains. ?Rg(2)(j)?, the contribution
of the jth chain segment to ?Rg(2)?, depends on the contour index about as
expected for Gaussian chains despite significant quantitative discrepancies that
express the swelling of these chains in water. Monomers central to the chain
contour occupy the center of the chain globule. The density profiles of chain
segments relative to their center of mass can show distinctive density
structuring for smaller chains due to the close proximity of central elements to
the globule center. However, that density structuring washes out for longer
chains where many chain elements additively contribute to the density profiles.
Gaussian chain models thus become more satisfactory for the density profiles for
longer chains.
PMID- 25121581
TI - Order reduction of the chemical master equation via balanced realisation.
AB - We consider a Markov process in continuous time with a finite number of discrete
states. The time-dependent probabilities of being in any state of the Markov
chain are governed by a set of ordinary differential equations, whose dimension
might be large even for trivial systems. Here, we derive a reduced ODE set that
accurately approximates the probabilities of subspaces of interest with a known
error bound. Our methodology is based on model reduction by balanced truncation
and can be considerably more computationally efficient than solving the chemical
master equation directly. We show the applicability of our method by analysing
stochastic chemical reactions. First, we obtain a reduced order model for the
infinitesimal generator of a Markov chain that models a reversible, monomolecular
reaction. Later, we obtain a reduced order model for a catalytic conversion of
substrate to a product (a so-called Michaelis-Menten mechanism), and compare its
dynamics with a rapid equilibrium approximation method. For this example, we
highlight the savings on the computational load obtained by means of the reduced
order model. Furthermore, we revisit the substrate catalytic conversion by
obtaining a lower-order model that approximates the probability of having
predefined ranges of product molecules. In such an example, we obtain an
approximation of the output of a model with 5151 states by a reduced model with
16 states. Finally, we obtain a reduced-order model of the Brusselator.
PMID- 25121582
TI - Neglected tropical diseases: a systematic evaluation of research capacity in
Nigeria.
AB - BACKGROUND: Nigeria carries the highest burden and diversity of neglected
tropical diseases (NTDs) in sub-Saharan Africa and is preparing to scale up its
efforts to control/eliminate these diseases. To achieve this it will require a
range of internal technical support and expertise for mapping, monitoring and
evaluating, operational research and documenting its success. In order to begin
to evaluate this potential in Nigeria, this study collated and analysed
information for lymphatic filariasis (LF), onchocerciasis, schistosomiasis and
soil-transmitted helminths (STH), which are currently being targeted with
preventive chemotherapy through mass drug administration (MDA).
METHODOLOGY/PRINCIPAL FINDINGS: Information from 299 scientific articles
published on the selected NTDs in 179 journals between January 2008 and September
2013 was extracted and systematically compiled into a geo-referenced database for
analysis and mapping. The highest number of articles was from the southern geo
political zones of the country. The majority of articles focused on one specific
disease, and schistosomiasis and STH were found to have the highest and most wide
ranging research output. The main type of study was parasitological, and the
least was biotechnological. Nigerian authors were mostly affiliated with
universities, and there was a wide range of international co-authors from Africa
and other regions, especially the USA and UK. The majority of articles were
published in journals with no known impact factor. CONCLUSIONS/SIGNIFICANCE: The
extensive database and series of maps on the research capacity within Nigeria
produced in this study highlights the current potential that exists, and needs to
be fully maximized for the control/elimination of NTDs in the country. This study
provides an important model approach that can be applied to other low and middle
income countries where NTDs are endemic, and NTD programmes require support from
the expertise within their own country, as well as internationally, to help raise
their profile and importance.
PMID- 25121583
TI - Illustrating anticipatory life cycle assessment for emerging photovoltaic
technologies.
AB - Current research policy and strategy documents recommend applying life cycle
assessment (LCA) early in research and development (R&D) to guide emerging
technologies toward decreased environmental burden. However, existing LCA
practices are ill-suited to support these recommendations. Barriers related to
data availability, rapid technology change, and isolation of environmental from
technical research inhibit application of LCA to developing technologies.
Overcoming these challenges requires methodological advances that help identify
environmental opportunities prior to large R&D investments. Such an anticipatory
approach to LCA requires synthesis of social, environmental, and technical
knowledge beyond the capabilities of current practices. This paper introduces a
novel framework for anticipatory LCA that incorporates technology forecasting,
risk research, social engagement, and comparative impact assessment, then applies
this framework to photovoltaic (PV) technologies. These examples illustrate the
potential for anticipatory LCA to prioritize research questions and help guide
environmentally responsible innovation of emerging technologies.
PMID- 25121585
TI - Direct spectroscopic observation of closed-shell singlet, open-shell singlet, and
triplet p-biphenylyloxenium ion.
AB - The photophysics and photochemistry of p-biphenylyl hydroxylamine hydrochloride
was studied using laser flash photolysis ranging from the femtosecond to the
microsecond time scale. The singlet excited state of this photoprecursor is
formed within 350 fs and partitions into three different transients that are
assigned to the p-biphenyloxy radical, the open-shell singlet p-biphenylyloxenium
ion, and the triplet p-biphenylyloxenium ion, having lifetimes of 40 MUs, 45 ps,
and 1.6 ns, respectively, in CH3CN. The open-shell singlet p-biphenylyloxenium
ion predominantly undergoes internal conversion to produce the closed-shell
singlet p-biphenylyloxenium ion, which has a lifetime of 5-20 ns. The longer
lived radical is unambiguously assigned by nanosecond time-resolved resonance
Raman (ns-TR(3)) spectroscopy, and the assignment of the short-lived singlet and
triplet oxenium ion transient absorptions are supported by matching time
dependent density functional theory (TD-DFT) predictions of the absorptions of
these species, as well as by product studies that implicate the intermediacy of
charged electrophilic intermediates. Product studies from photolysis give p
biphenylol as the major product and a chloride adduct as the major product when
NaCl is added as a trap. Thermolysis studies give p-biphenylol as a major
product, as well as water, ammonium, and chloro adducts. These studies provide a
rare direct look at a discrete oxenium ion intermediate and the first detection
of open-shell singlet and triplet configurations of an oxenium ion, as well as
providing an intriguing example of the importance of excited state dynamics in
governing the electronic state population of reactive intermediates.
PMID- 25121584
TI - Inference of transposable element ancestry.
AB - Most common methods for inferring transposable element (TE) evolutionary
relationships are based on dividing TEs into subfamilies using shared diagnostic
nucleotides. Although originally justified based on the "master gene" model of TE
evolution, computational and experimental work indicates that many of the
subfamilies generated by these methods contain multiple source elements. This
implies that subfamily-based methods give an incomplete picture of TE
relationships. Studies on selection, functional exaptation, and predictions of
horizontal transfer may all be affected. Here, we develop a Bayesian method for
inferring TE ancestry that gives the probability that each sequence was
replicative, its frequency of replication, and the probability that each extant
TE sequence came from each possible ancestral sequence. Applying our method to
986 members of the newly-discovered LAVA family of TEs, we show that there were
far more source elements in the history of LAVA expansion than subfamilies
identified using the CoSeg subfamily-classification program. We also identify
multiple replicative elements in the AluSc subfamily in humans. Our results
strongly indicate that a reassessment of subfamily structures is necessary to
obtain accurate estimates of mutation processes, phylogenetic relationships and
historical times of activity.
PMID- 25121586
TI - A new avenue toward androgen receptor pan-antagonists: C2 sterically hindered
substitution of hydroxy-propanamides.
AB - The androgen receptor (AR) represents the primary target for prostate cancer (PC)
treatment even when the disease progresses toward androgen-independent (AIPC) or
castration-resistant (CRPC) forms. Because small chemical changes in the
structure of nonsteroidal AR ligands determine the pharmacological responses of
AR, we developed a novel stereoselective synthetic strategy that allows
sterically hindered C2-substituted bicalutamide analogues to be obtained.
Biological and theoretical evaluations demonstrate that C2-substitution with
benzyl and phenyl moieties is a new, valuable option toward improving pan
antagonist behavior. Among the synthesized compounds, (R)-16m, when compared to
casodex, (R)-bicalutamide, and enzalutamide, displayed very promising in vitro
activity toward five different prostate cancer cell lines, all representative of
CPRC and AIPC typical mutations. Despite being less active than (R)-bicalutamide,
(R)-16m also displayed marked in vivo antitumor activity on VCaP xenografts and
thus it may serve as starting point for developing novel AR pan-antagonists.
PMID- 25121588
TI - Photocatalytic activity of ZnWO4: band structure, morphology and surface
modification.
AB - Photocatalytic degradation of organic contaminants is an important application
area in solar energy utilization. To improve material photocatalytic properties,
understanding their photocatalytic mechanism is indispensable. Here, the
photocatalytic performance of ZnWO4 nanocrystals was systematicly investigated by
the photodegradation of tetraethylated rhodamine (RhB) under simulated sunlight
irradiation, including the influence of morphology, AgO/ZnWO4 heterojunction and
comparison with CoWO4 nanowires. The results show that the photocatalytic
activity of ZnWO4 is higher than that of CoWO4, and the ZnWO4 nanorods exhibit
better photocatalytic activity than that of ZnWO4 nanowires. In addition, the
mechanism for the difference of the photocatalytic activity was also investigated
by comparison of their photoluminescence and photocurrents. AgO nanoparticles
were assembled uniformly on the surface of ZnWO4 nanowires to form a
heterojunction that exhibited enhanced photocatalytic activity under irradiation
at the initial stage. We found that a good photocatalyst should not only have an
active structure for electrons directly to transfer from the valence band to the
conduction band without the help of phonons but also a special electronic
configuration for the high mobility, to ensure more excited electrons and holes
in a catalytic reaction.
PMID- 25121587
TI - Black and white women in Maryland receive different treatment for cervical
cancer.
AB - PURPOSE: Despite an overall decrease in incidence, the death rate from cervical
cancer in the United States remains higher in black women than their white
counterparts. We examined the Maryland Cancer Registry (MCR) to determine
treatment factors that may explain differences in outcomes between races in the
state of Maryland. METHODS: Incident cervical cancers in the MCR 1992-2008 were
examined. Demographics, tumor characteristics and treatments were compared
between races and over time. RESULTS: Our analysis included 2034 (1301 white, 733
black) patients. Black women were more likely to have locally advanced or
metastatic disease at diagnosis (p<0.01). They were more likely to receive any
radiation or chemotherapy combined with radiation and less likely to receive
surgery (p<0.01). When adjusted for stage and insurance status black women had
1.50 (95% CI 1.20-1.87) times the odds of receiving radiation and 1.43 (95% CI
1.11-1.82) times the odds of receiving chemotherapy. Black women with cervical
cancer had 0.51 times the adjusted odds (95% CI 0.41-0.65) of receiving surgery
compared to white women. Racial differences in treatment did not change
significantly over time. CONCLUSIONS: Surgical treatment for newly diagnosed
cervical cancer in the state of Maryland was significantly less common amongst
black women than white during our study period. Equivalent treatments are not
being administered to white and black patients with cervical cancer in Maryland.
Differences in care may contribute to racial disparities in outcomes for women
with cervical cancer.
PMID- 25121589
TI - Factors associated with appointment non-adherence among African-Americans with
severe, poorly controlled hypertension.
AB - BACKGROUND: Missed appointments are associated with an increased risk of
hospitalization and mortality. Despite its widespread prevalence, little data
exists regarding factors related to appointment non-adherence among hypertensive
African-Americans. OBJECTIVE: To investigate factors associated with appointment
non-adherence among African-Americans with severe, poorly controlled
hypertension. DESIGN AND PARTICIPANTS: A cross-sectional survey of 185 African
Americans admitted to an urban medical center in Maryland, with severe, poorly
controlled hypertension from 1999-2004. Categorical and continuous variables were
compared using chi-square and t-tests. Adjusted multivariable logistic regression
was used to assess correlates of appointment non-adherence. MAIN OUTCOME
MEASURES: Appointment non-adherence was the primary outcome and was defined as
patient-report of missing greater than 3 appointments out of 10 during their
lifetime. RESULTS: Twenty percent of participants (n = 37) reported missing more
than 30% of their appointments. Patient characteristics independently associated
with a higher odds of appointment non-adherence included not finishing high
school (Odds ratio [OR] = 3.23 95% confidence interval [CI] (1.33-7.69),
hypertension knowledge ([OR] = 1.20 95% CI: 1.01-1.42), lack of insurance ([OR]
= 6.02 95% CI: 1.83-19.88), insurance with no medication coverage ([OR] = 5.08
95% CI: 1.05-24.63), cost of discharge medications ([OR] = 1.20 95% CI: 1.01
1.42), belief that anti-hypertensive medications do not work ([OR] = 3.67 95%
CI: 1.16-11.7), experience of side effects ([OR] = 3.63 95% CI: 1.24-10.62),
medication non-adherence ([OR] = 11.31 95% CI: 3.87-33.10). Substance abuse was
not associated with appointment non-adherence ([OR] = 1.05 95% CI: 0.43-2.57).
CONCLUSIONS: Appointment non-adherence among African-Americans with poorly
controlled hypertension was associated with many markers of inadequate access to
healthcare, knowledge, attitudes and beliefs.
PMID- 25121590
TI - EBNA3C augments Pim-1 mediated phosphorylation and degradation of p21 to promote
B-cell proliferation.
AB - Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, can latently infect the
human population. EBV is associated with several types of malignancies
originating from lymphoid and epithelial cell types. EBV latent antigen 3C
(EBNA3C) is essential for EBV-induced immortalization of B-cells. The Moloney
murine leukemia provirus integration site (PIM-1), which encodes an oncogenic
serine/threonine kinase, is linked to several cellular functions involving cell
survival, proliferation, differentiation, and apoptosis. Notably, enhanced
expression of Pim-1 kinase is associated with numerous hematological and non
hematological malignancies. A higher expression level of Pim-1 kinase is
associated with EBV infection, suggesting a crucial role for Pim-1 in EBV-induced
tumorigenesis. We now demonstrate a molecular mechanism which reveals a direct
role for EBNA3C in enhancing Pim-1 expression in EBV-infected primary B-cells. We
also showed that EBNA3C is physically associated with Pim-1 through its amino
terminal domain, and also forms a molecular complex in B-cells. EBNA3C can
stabilize Pim-1 through abrogation of the proteasome/Ubiquitin pathway. Our
results demonstrate that EBNA3C enhances Pim-1 mediated phosphorylation of p21 at
the Thr145 residue. EBNA3C also facilitated the nuclear localization of Pim-1,
and promoted EBV transformed cell proliferation by altering Pim-1 mediated
regulation of the activity of the cell-cycle inhibitor p21/WAF1. Our study
demonstrated that EBNA3C significantly induces Pim-1 mediated proteosomal
degradation of p21. A significant reduction in cell proliferation of EBV
transformed LCLs was observed upon stable knockdown of Pim-1. This study
describes a critical role for the oncoprotein Pim-1 in EBV-mediated oncogenesis,
as well as provides novel insights into oncogenic kinase-targeted therapeutic
intervention of EBV-associated cancers.
PMID- 25121591
TI - DNA binding and condensation properties of the herpes simplex virus type 1
triplex protein VP19C.
AB - Herpesvirus capsids are regular icosahedrons with a diameter of a 125 nm and are
made up of 162 capsomeres arranged on a T = 16 lattice. The capsomeres (VP5)
interact with the triplex structure, which is a unique structural feature of
herpesvirus capsid shells. The triplex is a heterotrimeric complex; one molecule
of VP19C and two of VP23 form a three-pronged structure that acts to stabilize
the capsid shell through interactions with adjacent capsomeres. VP19C interacts
with VP23 and with the major capsid protein VP5 and is required for the nuclear
localization of VP23. Mutation of VP19C results in the abrogation of capsid shell
synthesis. Analysis of the sequence of VP19C showed the N-terminus of VP19C is
very basic and glycine rich. It was hypothesized that this domain could
potentially bind to DNA. In this study an electrophoretic mobility shift assay
(EMSA) and a DNA condensation assay were performed to demonstrate that VP19C can
bind DNA. Purified VP19C was able to bind to both a DNA fragment of HSV-1 origin
as well as a bacterial plasmid sequence indicating that this activity is non
specific. Ultra-structural imaging of the nucleo-protein complexes revealed that
VP19C condensed the DNA and forms toroidal DNA structures. Both the DNA binding
and condensing properties of VP19C were mapped to the N-terminal 72 amino acids
of the protein. Mutational studies revealed that the positively charged arginine
residues in this N-terminal domain are required for this binding. This DNA
binding activity, which resides in a non-conserved region of the protein could be
required for stabilization of HSV-1 DNA association in the capsid shell.
PMID- 25121592
TI - Discovery of a eukaryotic pyrroloquinoline quinone-dependent oxidoreductase
belonging to a new auxiliary activity family in the database of carbohydrate
active enzymes.
AB - Pyrroloquinoline quinone (PQQ) is a redox cofactor utilized by a number of
prokaryotic dehydrogenases. Not all prokaryotic organisms are capable of
synthesizing PQQ, even though it plays important roles in the growth and
development of many organisms, including humans. The existence of PQQ-dependent
enzymes in eukaryotes has been suggested based on homology studies or the
presence of PQQ-binding motifs, but there has been no evidence that such enzymes
utilize PQQ as a redox cofactor. However, during our studies of hemoproteins, we
fortuitously discovered a novel PQQ-dependent sugar oxidoreductase in a mushroom,
the basidiomycete Coprinopsis cinerea. The enzyme protein has a signal peptide
for extracellular secretion and a domain for adsorption on cellulose, in addition
to the PQQ-dependent sugar dehydrogenase and cytochrome domains. Although this
enzyme shows low amino acid sequence homology with known PQQ-dependent enzymes,
it strongly binds PQQ and shows PQQ-dependent activity. BLAST search uncovered
the existence of many genes encoding homologous proteins in bacteria, archaea,
amoebozoa, and fungi, and phylogenetic analysis suggested that these
quinoproteins may be members of a new family that is widely distributed not only
in prokaryotes, but also in eukaryotes.
PMID- 25121593
TI - Oridonin attenuates Abeta1-42-induced neuroinflammation and inhibits NF-kappaB
pathway.
AB - Neuroinflammation induced by beta-amyloid (Abeta) plays a critical role in the
pathogenesis of Alzheimer's disease (AD), and inhibiting Abeta-induced
neuroinflammation serves as a potential strategy for the treatment of AD.
Oridonin (Ori), a compound of Rabdosia rubescens, has been shown to exert anti
inflammatory effects. In this study, we demonstrated that Ori inhibited glial
activation and decreased the release of inflammatory cytokines in the hippocampus
of Abeta1-42-induced AD mice. In addition, Ori inhibited the NF-kappaB pathway
and Abeta1-42-induced apoptosis. Furthermore, Ori could attenuate memory deficits
in Abeta1-42-induced AD mice. In conclusion, our study demonstrated that Ori
inhibited the neuroinflammation and attenuated memory deficits induced by Abeta1
42, suggesting that Ori might be a promising candidate for AD treatment.
PMID- 25121594
TI - Expression analysis of a stress-related phosphoinositide-specific phospholipase C
gene in wheat (Triticum aestivum L.).
AB - Plant phosphoinositide-specific phospholipases C (PI-PLCs) function in several
essential plant processes associated with either development or environmental
stress. In this report, we examined the expression patterns of TaPLC1 under
drought and high salinity stress at the transcriptional and post-transcriptional
levels. TaPLC1 mRNA was expressed in all wheat organs examined. U73122 and
edelfosine, the PLC inhibitor, impaired seedling growth and enhanced seedling
sensitivity to drought and high salinity stress. Though TaPLC1 expression in
wheat was lowest at the seedling stage, it was strongly induced under conditions
of stress. When 6-day-old wheat seedlings were treated with 200 mM NaCl or 20%
(w/v) PEG 6000 for 6 or 12 h, respectively, the TaPLC1 transcript level increased
by 16-fold compared to the control. Western blotting showed that the TaPLC
protein concentration was also maintained at a high level from 24 to 48 h during
stress treatment. Together, our results indicate the possible biological
functions of TaPLC1 in regulating seedling growth and the response to drought and
salinity stress.
PMID- 25121596
TI - Vaccine strategies for the control and prevention of Japanese encephalitis in
Mainland China, 1951-2011.
AB - Japanese encephalitis (JE) is arguably one of the most serious viral encephalitis
diseases worldwide. China has a long history of high prevalence of Japanese
encephalitis, with thousands of cases reported annually and incidence rates often
exceeding 15/100,000. In global terms, the scale of outbreaks and high incidence
of these pandemics has almost been unique, placing a heavy burden on the Chinese
health authorities. However, the introduction of vaccines, developed in China,
combined with an intensive vaccination program initiated during the 1970s, as
well as other public health interventions, has dramatically decreased the
incidence from 20.92/100,000 in 1971, to 0.12/100,000 in 2011. Moreover, in less
readily accessible areas of China, changes to agricultural practices designed to
reduce chances of mosquito bites as well as mosquito population densities have
also been proven effective in reducing local JE incidence. This unprecedented
public health achievement has saved many lives and provided valuable experience
that could be directly applicable to the control of vector-borne diseases around
the world. Here, we review and discuss strategies for promotion and expansion of
vaccination programs to reduce the incidence of JE even further, for the benefit
of health authorities throughout Asia and, potentially, worldwide.
PMID- 25121595
TI - A neural network approach to fMRI binocular visual rivalry task analysis.
AB - The purpose of this study was to investigate whether artificial neural networks
(ANN) are able to decode participants' conscious experience perception from brain
activity alone, using complex and ecological stimuli. To reach the aim we
conducted pattern recognition data analysis on fMRI data acquired during the
execution of a binocular visual rivalry paradigm (BR). Twelve healthy
participants were submitted to fMRI during the execution of a binocular non
rivalry (BNR) and a BR paradigm in which two classes of stimuli (faces and
houses) were presented. During the binocular rivalry paradigm, behavioral
responses related to the switching between consciously perceived stimuli were
also collected. First, we used the BNR paradigm as a functional localizer to
identify the brain areas involved the processing of the stimuli. Second, we
trained the ANN on the BNR fMRI data restricted to these regions of interest.
Third, we applied the trained ANN to the BR data as a 'brain reading' tool to
discriminate the pattern of neural activity between the two stimuli. Fourth, we
verified the consistency of the ANN outputs with the collected behavioral
indicators of which stimulus was consciously perceived by the participants. Our
main results showed that the trained ANN was able to generalize across the two
different tasks (i.e. BNR and BR) and to identify with high accuracy the
cognitive state of the participants (i.e. which stimulus was consciously
perceived) during the BR condition. The behavioral response, employed as control
parameter, was compared with the network output and a statistically significant
percentage of correspondences (p-value <0.05) were obtained for all subjects. In
conclusion the present study provides a method based on multivariate pattern
analysis to investigate the neural basis of visual consciousness during the BR
phenomenon when behavioral indicators lack or are inconsistent, like in disorders
of consciousness or sedated patients.
PMID- 25121597
TI - CDK4 amplification predicts recurrence of well-differentiated liposarcoma of the
abdomen.
AB - BACKGROUND: The absence of CDK4 amplification in liposarcomas is associated with
favorable prognosis. We aimed to identify the factors associated with tumor
recurrence in patients with well-differentiated (WD) and dedifferentiated (DD)
liposarcomas. METHODS: From 2000 to 2010, surgical resections for 101 WD and DD
liposarcomas were performed. Cases in which complete surgical resections with
curative intent were carried out were selected. MDM2 and CDK4 gene amplification
were analyzed by quantitative real-time polymerase chain reaction (Q-PCR).
RESULTS: There were 31 WD and 17 DD liposarcomas. Locoregional recurrence was
observed in 11 WD and 3 DD liposarcomas. WD liposarcomas showed better patient
survival compared to DD liposarcomas (P<0.05). Q-PCR analysis of the liposarcomas
revealed the presence of CDK4 amplification in 44 cases (91.7%) and MDM2
amplification in 46 cases (95.8%). WD liposarcomas with recurrence after surgical
resection had significantly higher levels of CDK4 amplification compared to those
without recurrence (P = 0.041). High level of CDK4 amplification (cases with CDK4
amplification higher than the median 7.54) was associated with poor recurrence
free survival compared to low CDK4 amplification in both univariate (P = 0.012)
and multivariate analyses (P = 0.020). CONCLUSIONS: Level of CDK4 amplification
determined by Q-PCR was associated with the recurrence of WD liposarcomas after
surgical resection.
PMID- 25121598
TI - Logarithmic and power law input-output relations in sensory systems with fold
change detection.
AB - Two central biophysical laws describe sensory responses to input signals. One is
a logarithmic relationship between input and output, and the other is a power law
relationship. These laws are sometimes called the Weber-Fechner law and the
Stevens power law, respectively. The two laws are found in a wide variety of
human sensory systems including hearing, vision, taste, and weight perception;
they also occur in the responses of cells to stimuli. However the mechanistic
origin of these laws is not fully understood. To address this, we consider a
class of biological circuits exhibiting a property called fold-change detection
(FCD). In these circuits the response dynamics depend only on the relative change
in input signal and not its absolute level, a property which applies to many
physiological and cellular sensory systems. We show analytically that by changing
a single parameter in the FCD circuits, both logarithmic and power-law
relationships emerge; these laws are modified versions of the Weber-Fechner and
Stevens laws. The parameter that determines which law is found is the steepness
(effective Hill coefficient) of the effect of the internal variable on the
output. This finding applies to major circuit architectures found in biological
systems, including the incoherent feed-forward loop and nonlinear integral
feedback loops. Therefore, if one measures the response to different fold changes
in input signal and observes a logarithmic or power law, the present theory can
be used to rule out certain FCD mechanisms, and to predict their cooperativity
parameter. We demonstrate this approach using data from eukaryotic chemotaxis
signaling.
PMID- 25121600
TI - Pectinmethylesterases (PME) and pectinmethylesterase inhibitors (PMEI) enriched
during phloem fiber development in flax (Linum usitatissimum).
AB - Flax phloem fibers achieve their length by intrusive-diffusive growth, which
requires them to penetrate the extracellular matrix of adjacent cells. Fiber
elongation therefore involves extensive remodelling of cell walls and middle
lamellae, including modifying the degree and pattern of methylesterification of
galacturonic acid (GalA) residues of pectin. Pectin methylesterases (PME) are
important enzymes for fiber elongation as they mediate the demethylesterification
of GalA in muro, in either a block-wise fashion or in a random fashion. Our
objective was to identify PMEs and PMEIs that mediate phloem fiber elongation in
flax. For this purpose, we measured transcript abundance of candidate genes at
nine different stages of stem and fiber development and found sets of genes
enriched during fiber elongation and maturation as well as during xylem
development. We expressed one of the flax PMEIs in E. coli and demonstrated that
it was able to inhibit most of the native PME activity in the upper portion of
the flax stem. These results identify key genetic components of the intrusive
growth process and define targets for fiber engineering and crop improvement.
PMID- 25121599
TI - An otx/nodal regulatory signature for posterior neural development in ascidians.
AB - In chordates, neural induction is the first step of a complex developmental
process through which ectodermal cells acquire a neural identity. In ascidians,
FGF-mediated neural induction occurs at the 32-cell stage in two blastomere
pairs, precursors respectively of anterior and posterior neural tissue. We
combined molecular embryology and cis-regulatory analysis to unveil in the
ascidian Ciona intestinalis the remarkably simple proximal genetic network that
controls posterior neural fate acquisition downstream of FGF. We report that the
combined action of two direct FGF targets, the TGFbeta factor Nodal, acting via
Smad- and Fox-binding sites, and the transcription factor Otx suffices to trigger
ascidian posterior neural tissue formation. Moreover, we found that this strategy
is conserved in the distantly related ascidian Phallusia mammillata, in spite of
extreme sequence divergence in the cis-regulatory sequences involved. Our results
thus highlight that the modes of gene regulatory network evolution differ with
the evolutionary scale considered. Within ascidians, developmental regulatory
networks are remarkably robust to genome sequence divergence. Between ascidians
and vertebrates, major fate determinants, such as Otx and Nodal, can be co-opted
into different networks. Comparative developmental studies in ascidians with
divergent genomes will thus uncover shared ascidian strategies, and contribute to
a better understanding of the diversity of developmental strategies within
chordates.
PMID- 25121601
TI - SNP identification by transcriptome sequencing and candidate gene-based
association analysis for heat tolerance in the bay scallop Argopecten irradians.
AB - The northern bay scallop Argopecten irradians irradians (Lamarck) and the
southern bay scallop Argopecten irradians concentricus (Say) were introduced into
China in the 1980s and 1990s, and are now major aquaculture molluscs in China.
Here, we report the transcriptome sequencing of the two subspecies and the
subsequent association analysis on candidate gene on the trait of heat tolerance.
In total, RNA from six tissues of 67 and 42 individuals of northern and southern
bay scallops, respectively, were used and 55.5 and 34.9 million raw reads were
generated, respectively. There were 82,267 unigenes produced in total, of which
32,595 were annotated. Altogether, 32,206 and 23,312 high-quality SNPs were
identified for northern and southern bay scallops, respectively. For case-control
analysis, two intercrossed populations were heat stress treated, and both heat
susceptible and heat-resistant individuals were collected. According to
annotation and SNP allele frequency analysis, 476 unigenes were selected, and 399
pairs of primers were designed. Genotyping was conducted using the high
resolution melting method, and Fisher's exact test was performed for allele
frequency comparison between the heat-susceptible and heat-resistant groups. SNP
all-53308-760 T/C showed a significant difference in allele frequency between the
heat-susceptible and heat-resistant groups. Notably, considerable difference in
allele frequency at this locus was also observed between the sequenced natural
populations. These results suggest that SNP all-53308-760 T/C may be related to
the heat tolerance of the bay scallop. Moreover, quantitative expression analysis
revealed that the expression level of all-53308 was negatively correlated with
heat tolerance of the bay scallop.
PMID- 25121602
TI - Conserving plants in gene banks and nature: investigating complementarity with
Trifolium thompsonii Morton.
AB - A standard conservation strategy for plant genetic resources integrates in situ
(on-farm or wild) and ex situ (gene or field bank) approaches. Gene bank managers
collect ex situ accessions that represent a comprehensive snap shot of the
genetic diversity of in situ populations at a given time and place. Although
simple in theory, achieving complementary in situ and ex situ holdings is
challenging. Using Trifolium thompsonii as a model insect-pollinated herbaceous
perennial species, we used AFLP markers to compare genetic diversity and
structure of ex situ accessions collected at two time periods (1995, 2004) from
four locations, with their corresponding in situ populations sampled in 2009. Our
goal was to assess the complementarity of the two approaches. We examined how
gene flow, selection and genetic drift contributed to population change. Across
locations, we found no difference in diversity between ex situ and in situ
samples. One population showed a decline in genetic diversity over the 15 years
studied. Population genetic differentiation among the four locations was
significant, but weak. Association tests suggested infrequent, long distance gene
flow. Selection and drift occurred, but differences due to spatial effects were
three times as strong as differences attributed to temporal effects, and
suggested recollection efforts could occur at intervals greater than fifteen
years. An effective collecting strategy for insect pollinated herbaceous
perennial species was to sample >150 plants, equalize maternal contribution, and
sample along random transects with sufficient space between plants to minimize
intrafamilial sampling. Quantifying genetic change between ex situ and in situ
accessions allows genetic resource managers to validate ex situ collecting and
maintenance protocols, develop appropriate recollection intervals, and provide an
early detection mechanism for identifying problematic conditions that can be
addressed to prevent further decline in vulnerable in situ populations.
PMID- 25121603
TI - Top-down inputs enhance orientation selectivity in neurons of the primary visual
cortex during perceptual learning.
AB - Perceptual learning has been used to probe the mechanisms of cortical plasticity
in the adult brain. Feedback projections are ubiquitous in the cortex, but little
is known about their role in cortical plasticity. Here we explore the hypothesis
that learning visual orientation discrimination involves learning-dependent
plasticity of top-down feedback inputs from higher cortical areas, serving a
different function from plasticity due to changes in recurrent connections within
a cortical area. In a Hodgkin-Huxley-based spiking neural network model of visual
cortex, we show that modulation of feedback inputs to V1 from higher cortical
areas results in shunting inhibition in V1 neurons, which changes the response
properties of V1 neurons. The orientation selectivity of V1 neurons is enhanced
without changing orientation preference, preserving the topographic organizations
in V1. These results provide new insights to the mechanisms of plasticity in the
adult brain, reconciling apparently inconsistent experiments and providing a new
hypothesis for a functional role of the feedback connections.
PMID- 25121605
TI - Temperature and food influence shell growth and mantle gene expression of shell
matrix proteins in the pearl oyster Pinctada margaritifera.
AB - In this study, we analyzed the combined effect of microalgal concentration and
temperature on the shell growth of the bivalve Pinctada margaritifera and the
molecular mechanisms underlying this biomineralization process. Shell growth was
measured after two months of rearing in experimental conditions, using calcein
staining of the calcified structures. Molecular mechanisms were studied though
the expression of 11 genes encoding proteins implicated in the biomineralization
process, which was assessed in the mantle. We showed that shell growth is
influenced by both microalgal concentration and temperature, and that these
environmental factors also regulate the expression of most of the genes studied.
Gene expression measurement of shell matrix protein thereby appears to be an
appropriate indicator for the evaluation of the biomineralization activity in the
pearl oyster P. margaritifera under varying environmental conditions. This study
provides valuable information on the molecular mechanisms of mollusk shell growth
and its environmental control.
PMID- 25121604
TI - Circadian regulation of myocardial sarcomeric Titin-cap (Tcap, telethonin):
identification of cardiac clock-controlled genes using open access bioinformatics
data.
AB - Circadian rhythms are important for healthy cardiovascular physiology and are
regulated at the molecular level by a circadian clock mechanism. We and others
previously demonstrated that 9-13% of the cardiac transcriptome is rhythmic over
24 h daily cycles; the heart is genetically a different organ day versus night.
However, which rhythmic mRNAs are regulated by the circadian mechanism is not
known. Here, we used open access bioinformatics databases to identify 94
transcripts with expression profiles characteristic of CLOCK and BMAL1 targeted
genes, using the CircaDB website and JTK_Cycle. Moreover, 22 were highly
expressed in the heart as determined by the BioGPS website. Furthermore, 5 heart
enriched genes had human/mouse conserved CLOCK:BMAL1 promoter binding sites (E
boxes), as determined by UCSC table browser, circadian mammalian
promoter/enhancer database PEDB, and the European Bioinformatics Institute
alignment tool (EMBOSS). Lastly, we validated findings by demonstrating that
Titin cap (Tcap, telethonin) was targeted by transcriptional activators CLOCK and
BMAL1 by showing 1) Tcap mRNA and TCAP protein had a diurnal rhythm in murine
heart; 2) cardiac Tcap mRNA was rhythmic in animals kept in constant darkness; 3)
Tcap and control Per2 mRNA expression and cyclic amplitude were blunted in
Clock(Delta19/Delta19) hearts; 4) BMAL1 bound to the Tcap promoter by ChIP assay;
5) BMAL1 bound to Tcap promoter E-boxes by biotinylated oligonucleotide assay;
and 6) CLOCK and BMAL1 induced tcap expression by luciferase reporter assay. Thus
this study identifies circadian regulated genes in silico, with validation of
Tcap, a critical regulator of cardiac Z-disc sarcomeric structure and function.
PMID- 25121606
TI - Impact of hormone-associated resistance to activated protein C on the thrombotic
potential of oral contraceptives: a prospective observational study.
AB - INTRODUCTION: The increased thrombotic risk of oral contraceptives (OC) has been
attributed to various alterations of the hemostatic system, including acquired
resistance to activated protein C (APC). To evaluate to what extent OC-associated
APC resistance induces a prothrombotic state we monitored plasma levels of
thrombin and molecular markers specific for thrombin formation in women starting
OC use. Elevated plasma levels of thrombin have been reported to characterize
situations of high thrombotic risk such as trauma-induced hypercoagulability, but
have not yet been studied during OC use. PATIENTS AND METHODS: Blood samples were
collected prospectively from healthy women (n = 21) before and during three
menstruation cycles after start of OC. APC resistance was evaluated using a
thrombin generation-based assay. Plasma levels of thrombin and APC were directly
measured using highly sensitive oligonucleotide-based enzyme capture assay (OECA)
technology. Thrombin generation markers and other hemostasis parameters were
measured additionally. RESULTS: All women developed APC resistance as indicated
by an increased APC sensitivity ratio compared with baseline after start of OC (p
= 0.0003). Simultaneously, plasma levels of thrombin, prothrombin fragment 1+2,
and of thrombin-antithrombin complexes did not change, ruling out increased
thrombin formation. APC plasma levels were also not influenced by OC use, giving
further evidence that increased thrombin formation did not occur. CONCLUSIONS: In
the majority of OC users no enhanced thrombin formation occurs despite the
development of APC resistance. It cannot be ruled out, however, that thrombin
formation might occur to a greater extent in the presence of additional risk
factors. If this were the case, endogenous thrombin levels might be a potential
biomarker candidate to identify women at high thrombotic risk during OC
treatment. Large-scale studies are required to assess the value of plasma levels
of thrombin as predictors of OC-associated thrombotic risk.
PMID- 25121607
TI - The prevalence and magnitude of impaired cutaneous sensation across the hand in
the chronic period post-stroke.
AB - Sensation is commonly impaired immediately post-stroke but little is known about
the long-term changes in cutaneous sensation that have the capacity to adversely
impact independence and motor-function. We investigated cutaneous sensory
thresholds across the hand in the chronic post-stroke period. Cutaneous sensation
was assessed in 42 community-dwelling stroke patients and compared to 36 healthy
subjects. Sensation was tested with calibrated monofilaments at 6 sites on the
hand that covered the median, ulnar and radial innervation territories and
included both glabrous (hairless) and hairy skin. The motor-function of stroke
patients was assessed with the Wolf Motor Function Test and the upper-limb motor
Fugl-Meyer Assessment. Impaired cutaneous sensation was defined as monofilament
thresholds >3 SD above the mean of healthy subjects and good sensation was <= 3
SD. Cutaneous sensation was impaired for 33% of patients and was 40-84% worse on
the more-affected side compared to healthy subjects depending on the site
(p<0.05). When the stroke patient data were pooled cutaneous sensation fell
within the healthy range, although ~ 1/3 of patients were classified with
impaired sensation. Classification by motor-function revealed low levels of
impaired sensation. The magnitude of sensory loss was only apparent when the
sensory-function of stroke patients was classified as good or impaired. Sensation
was most impaired on the dorsum of the hand where age-related changes in
monofilament thresholds are minimal in healthy subjects. Although patients with
both high and low motor-function had poor cutaneous sensation, overall patients
with low motor-function had poorer cutaneous sensation than those with higher
motor-function, and relationships were found between motor impairments and
sensation at the fingertip and palm. These results emphasize the importance of
identifying the presence and magnitude of cutaneous sensory impairments in the
chronic period after stroke.
PMID- 25121609
TI - Largest genetic survey to date shows major success for giant panda breeding
programs.
PMID- 25121608
TI - Relationships between the ABC-exporter HetC and peptides that regulate the
spatiotemporal pattern of heterocyst distribution in Anabaena.
AB - In the model cyanobacterium Anabaena sp. PCC 7120, cells called heterocysts that
are specialized in the fixation of atmospheric nitrogen differentiate from
vegetative cells of the filament in the absence of combined nitrogen. Heterocysts
follow a specific distribution pattern along the filament, and a number of
regulators have been identified that influence the heterocyst pattern. PatS and
HetN, expressed in the differentiating cells, inhibit the differentiation of
neighboring cells. At least PatS appears to be processed and transferred from
cell to cell. HetC is similar to ABC exporters and is required for
differentiation. We present an epistasis analysis of these regulatory genes and
of genes, hetP and asr2819, successively downstream from hetC, and we have
studied the localization of HetC and HetP by use of GFP fusions. Inactivation of
patS, but not of hetN, allowed differentiation to proceed in a hetC background,
whereas inactivation of hetC in patS or patS hetN backgrounds decreased the
frequency of contiguous proheterocysts. A HetC-GFP protein is localized to the
heterocysts and especially near their cell poles, and a putative HetC peptidase
domain was required for heterocyst differentiation but not for HetC-GFP
localization. hetP is also required for heterocyst differentiation. A HetP-GFP
protein localized mostly near the heterocyst poles. ORF asr2819, which we denote
patC, encodes an 84-residue peptide and is induced upon nitrogen step-down.
Inactivation of patC led to a late spreading of the heterocyst pattern. Whereas
HetC and HetP appear to have linked functions that allow heterocyst
differentiation to progress, PatC may have a role in selecting sites of
differentiation, suggesting that these closely positioned genes may be
functionally related.
PMID- 25121610
TI - The HIV-1 envelope transmembrane domain binds TLR2 through a distinct
dimerization motif and inhibits TLR2-mediated responses.
AB - HIV-1 uses a number of means to manipulate the immune system, to avoid
recognition and to highjack signaling pathways. HIV-1 infected cells show limited
Toll-Like Receptor (TLR) responsiveness via as yet unknown mechanisms. Using
biochemical and biophysical approaches, we demonstrate that the trans-membrane
domain (TMD) of the HIV-1 envelope (ENV) directly interacts with TLR2 TMD within
the membrane milieu. This interaction attenuates TNFalpha, IL-6 and MCP-1
secretion in macrophages, induced by natural ligands of TLR2 both in in vitro and
in vivo models. This was associated with decreased levels of ERK phosphorylation.
Furthermore, mutagenesis demonstrated the importance of a conserved GxxxG motif
in driving this interaction within the membrane milieu. The administration of the
ENV TMD in vivo to lipotechoic acid (LTA)/Galactosamine-mediated septic mice
resulted in a significant decrease in mortality and in tissue damage, due to the
weakening of systemic macrophage activation. Our findings suggest that the TMD of
ENV is involved in modulation of the innate immune response during HIV infection.
Furthermore, due to the high functional homology of viral ENV proteins this
function may be a general character of viral-induced immune modulation.
PMID- 25121611
TI - Exogenous lactate supply affects lactate kinetics of rainbow trout, not swimming
performance.
AB - Intense swimming causes circulatory lactate accumulation in rainbow trout because
lactate disposal (Rd) is not stimulated as strongly as lactate appearance (Ra).
This mismatch suggests that maximal Rd is limited by tissue capacity to
metabolize lactate. This study uses exogenous lactate to investigate what
constrains maximal Rd and minimal Ra. Our goals were to determine how exogenous
lactate affects: 1) Ra and Rd of lactate under baseline conditions or during
graded swimming, and 2) exercise performance (critical swimming speed, Ucrit) and
energetics (cost of transport, COT). Results show that exogenous lactate allows
swimming trout to boost maximal Rd lactate by 40% and reach impressive rates of
56 MUmol.kg(-1).min(-1). This shows that the metabolic capacity of tissues for
lactate disposal is not responsible for setting the highest Rd normally observed
after intense swimming. Baseline endogenous Ra (resting in normoxic water) is not
significantly reduced by exogenous lactate supply. Therefore, trout have an
obligatory need to produce lactate, either as a fuel for oxidative tissues and/or
from organs relying on glycolysis. Exogenous lactate does not affect Ucrit or
COT, probably because it acts as a substitute for glucose and lipids rather than
extra fuel. We conclude that the observed 40% increase in Rd lactate is made
possible by accelerating lactate entry into oxidative tissues via monocarboxylate
transporters (MCTs). This observation together with the weak expression of MCTs
and the phenomenon of white muscle lactate retention show that lactate metabolism
of rainbow trout is significantly constrained by transmembrane transport.
PMID- 25121612
TI - Cold water immersion enhances recovery of submaximal muscle function after
resistance exercise.
AB - We investigated the effect of cold water immersion (CWI) on the recovery of
muscle function and physiological responses after high-intensity resistance
exercise. Using a randomized, cross-over design, 10 physically active men
performed high-intensity resistance exercise followed by one of two recovery
interventions: 1) 10 min of CWI at 10 degrees C or 2) 10 min of active recovery
(low-intensity cycling). After the recovery interventions, maximal muscle
function was assessed after 2 and 4 h by measuring jump height and isometric
squat strength. Submaximal muscle function was assessed after 6 h by measuring
the average load lifted during 6 sets of 10 squats at 80% of 1 repetition
maximum. Intramuscular temperature (1 cm) was also recorded, and venous blood
samples were analyzed for markers of metabolism, vasoconstriction, and muscle
damage. CWI did not enhance recovery of maximal muscle function. However, during
the final three sets of the submaximal muscle function test, participants lifted
a greater load (P < 0.05, Cohen's effect size: 1.3, 38%) after CWI compared with
active recovery. During CWI, muscle temperature decreased ~7 degrees C below
postexercise values and remained below preexercise values for another 35 min.
Venous blood O2 saturation decreased below preexercise values for 1.5 h after
CWI. Serum endothelin-1 concentration did not change after CWI, whereas it
decreased after active recovery. Plasma myoglobin concentration was lower,
whereas plasma IL-6 concentration was higher after CWI compared with active
recovery. These results suggest that CWI after resistance exercise allows
athletes to complete more work during subsequent training sessions, which could
enhance long-term training adaptations.
PMID- 25121613
TI - Pushing the limits of blood pressure control under severe heat stress. Focus on
"Active and passive heat stress similarly compromise tolerance to a simulated
hemorrhagic challenge".
PMID- 25121614
TI - Autophagy is essential to support skeletal muscle plasticity in response to
endurance exercise.
AB - Physical exercise is a stress that can substantially modulate cellular signaling
mechanisms to promote morphological and metabolic adaptations. Skeletal muscle
protein and organelle turnover is dependent on two major cellular pathways:
Forkhead box class O proteins (FOXO) transcription factors that regulate two main
proteolytic systems, the ubiquitin-proteasome, and the autophagy-lysosome
systems, including mitochondrial autophagy, and the MTORC1 signaling associated
with protein translation and autophagy inhibition. In recent years, it has been
well documented that both acute and chronic endurance exercise can affect the
autophagy pathway. Importantly, substantial efforts have been made to better
understand discrepancies in the literature on its modulation during exercise. A
single bout of endurance exercise increases autophagic flux when the duration is
long enough, and this response is dependent on nutritional status, since
autophagic flux markers and mRNA coding for actors involved in mitophagy are more
abundant in the fasted state. In contrast, strength and resistance exercises
preferentially raise ubiquitin-proteasome system activity and involve several
protein synthesis factors, such as the recently characterized DAGK for
mechanistic target of rapamycin activation. In this review, we discuss recent
progress on the impact of acute and chronic exercise on cell component turnover
systems, with particular focus on autophagy, which until now has been relatively
overlooked in skeletal muscle. We especially highlight the most recent studies on
the factors that can impact its modulation, including the mode of exercise and
the nutritional status, and also discuss the current limitations in the
literature to encourage further works on this topic.
PMID- 25121616
TI - The association of serum vitamin D concentration with serious complications after
noncardiac surgery.
AB - BACKGROUND: Vitamin D deficiency is a global health problem. Epidemiological
studies demonstrate that vitamin D is both cardioprotective and neuroprotective.
Vitamin D also plays a substantial role in innate and acquired immunity. Our goal
was to evaluate the association of serum vitamin D concentration on serious
postoperative complications and death in noncardiac surgical patients. METHODS:
We retrospectively analyzed the data of 3509 patients who had noncardiac surgery
at the Cleveland Clinic Main Campus and had a serum vitamin D measurement. The
relationship between serum vitamin D concentration and all-cause in-hospital
mortality, in-hospital cardiovascular morbidity, and serious in-hospital
infections was assessed as a common effect odds ratio (OR) by using a
multivariate generalized estimating equation model with adjustment for
demographic, medical history variables, and type and duration of surgery.
RESULTS: Higher vitamin D concentrations were associated with decreased odds of
in-hospital mortality/morbidity (P = 0.003). There was a linear reduction of the
corresponding common effect odds ratio (OR 0.93, 95% confidence interval, 0.88
0.97) for severe in-hospital outcomes for each 5 ng/mL increase in vitamin D
concentration over the range from 4 to 44 ng/mL. In addition, we found that the
odds versus patients with vitamin D <13 ng/mL (i.e., 1st quintile) were
significantly lower in patients with vitamin D 13-20, 20-27, 27-36, and > 36
ng/mL (i.e., 2nd-5th quintiles); the corresponding estimated ORs were 0.65 (99%
confidence interval, 0.43-0.98), 0.53 (0.35-0.80), 0.44 (0.28-0.70), and 0.49
(0.31-0.78), respectively. However, there was no statistically significant
difference among individual quintiles >13 ng/mL. CONCLUSIONS: Vitamin D
concentrations were associated with a composite of in-hospital death, serious
infections, and serious cardiovascular events in patients recovering from
noncardiac surgery. While causality cannot be determined from our retrospective
analysis, the association suggests that a large randomized trial of preoperative
vitamin D supplementation and postoperative outcomes is warranted.
PMID- 25121617
TI - Cooling strategies targeting trauma.
PMID- 25121615
TI - Cadherin cytoplasmic domains inhibit the cell surface localization of endogenous
E-cadherin, blocking desmosome and tight junction formation and inducing cell
dissociation.
AB - The downregulation of E-cadherin function has fundamental consequences with
respect to cancer progression, and occurs as part of the epithelial-mesenchymal
transition (EMT). In this study, we show that the expression of the Discosoma sp.
red fluorescent protein (DsRed)-tagged cadherin cytoplasmic domain in cells
inhibited the cell surface localization of endogenous E-cadherin, leading to
morphological changes, the inhibition of junctional assembly and cell
dissociation. These changes were associated with increased cell migration, but
were not accompanied by the down-regulation of epithelial markers and up
regulation of mesenchymal markers. Thus, these changes cannot be classified as
EMT. The cadherin cytoplasmic domain interacted with beta-catenin or plakoglobin,
reducing the levels of beta-catenin or plakoglobin associated with E-cadherin,
and raising the possibility that beta-catenin and plakoglobin sequestration by
these constructs induced E-cadherin intracellular localization. Accordingly, a
cytoplasmic domain construct bearing mutations that weakened the interactions
with beta-catenin or plakoglobin did not impair junction formation and adhesion,
indicating that the interaction with beta-catenin or plakoglobin was essential to
the potential of the constructs. E-cadherin-alpha-catenin chimeras that did not
require beta-catenin or plakoglobin for their cell surface transport restored
cell-cell adhesion and junction formation.
PMID- 25121618
TI - Long-term benefits versus side-effects from bone-targeted therapies for cancer
patients: minimizing risk while maximizing benefits.
AB - PURPOSE OF REVIEW: Bone-targeted therapies such as bisphosphonates and denosumab
are established in the treatment of cancer patients to prevent or delay skeletal
related events and improve quality of life. Along with these benefits of bone
targeted therapies, there are also known risks and adverse effects. RECENT
FINDINGS: Although historically bone-targeted therapy use has been limited to
palliation in patients with bone metastases, recent evidence suggests that these
agents may also have anti-cancer effects. This will likely lead to the greater
use of these agents in patients with earlier-stage disease. Increased use will
lead to more adverse effects. In particular, the risk of rare but severe
toxicities will become important. SUMMARY: This article explores strategies to
maximize the clinical benefit of such therapy while minimizing associated risks.
PMID- 25121621
TI - Edentulous persons, United States-1971.
AB - There were an estimated 22.6 million edentulous persons in the United States
according to the Health Interview Survey conducted in 1971. The Ju1y 1957-June
1958 survey estimate of the number of persons who were edentulous (had lost all
their natural teeth) was 21.9 million. Since in most instances it takes many
years of dental neglect for an individual to lose all his teeth, persons with no
teeth are heavily concentrated in the older age groups. For example, in 1971,86.3
percent (19.5 million) of the edentulous population were in the age group 45
years of age and older, while in 1957-58 the comparable figure was 85.2 percent.
Virtually every American will be affected during his or her lifetime by dental
decay or periodontal disease. Reports previously published in the Vital and
Health Statistics series contain national estimates of the prevalence, severity,
and effects of dental disease among U.S. adults. Based on dental examinations
conducted during 1960-62, it was estimated that approximately 20 million adults
had lost all their natural teeth. Of the remaining adults with at least one
natural tooth (approximately 90 million), about haIf had 18 or more decayed,
missing, or filled teeth. In addition, about three out of four of those with
natural teeth had periodontal disease, and about one out of four had an advanced
form of periodontal disease with pocket formations. The result of neglected
dental caries and advanced periodontal disease is the loss of teeth. Persons
using artificial dentures are considerably less efficient at chewing than persons
with healthy natural teeth. For the aged, artificial dentures mean a decrease in
masticator function at a time when an efficient dental function is increasingly
desirable due to changes in nutritional requirements. While the ultimate dental
health goaI is the eradication of dental disease, an important immediate goal is
the reduction of tooth Ioss. Tooth loss can usualIy be obviated by diagnosing and
treating dental disease in its early stages and by utilizing the preventive
measures now available.
PMID- 25121620
TI - Evaluation of an mHealth intervention aiming to improve health-related behavior
and sleep and reduce fatigue among airline pilots.
AB - OBJECTIVES: The aim of this study was to evaluate the effects of an mHealth
intervention (intervention using mobile technology) consisting of tailored advice
regarding exposure to daylight, sleep, physical activity, and nutrition, and
aiming to improve health-related behavior, thereby reducing sleep problems and
fatigue and improving health perception of airline pilots. METHODS: A randomized
controlled trial was conducted among 502 airline pilots. The intervention group
was given access to both the MORE Energy mobile application (app) with tailored
advice and a website with background information. The control group was directed
to a website with standard information about fatigue. Health-related behavior,
fatigue, sleep, and health perception outcomes were measured through online
questionnaires at baseline and at three and six months after baseline. The
effectiveness of the intervention was determined using linear and Poisson mixed
model analyses. RESULTS: After six months, compared to the control group, the
intervention group showed a significant improvement on fatigue (beta= -3.76,
P<0.001), sleep quality (beta= -0.59, P=0.007), strenuous physical activity
(beta=0.17, P=0.028), and snacking behavior (beta= -0.81, P<0.001). No
significant effects were found for other outcome measures. CONCLUSIONS: The MORE
Energy mHealth intervention reduced self-reported fatigue compared to a minimal
intervention. Some aspects of health-related behavior (physical activity and
snacking behavior) and sleep (sleep quality) improved as well, but most did not.
The results show offering tailored advice through an mHealth intervention is an
effective means to support employees who have to cope with irregular flight
schedules and circadian disruption. This kind of intervention might therefore
also be beneficial for other working populations with irregular working hours.
PMID- 25121619
TI - Optimization of photoactive protein Z for fast and efficient site-specific
conjugation of native IgG.
AB - Antibody conjugates have been used in a variety of applications from immunoassays
to drug conjugates. However, it is becoming increasingly clear that in order to
maximize an antibody's antigen binding ability and to produce homogeneous
antibody-conjugates, the conjugated molecule should be attached onto IgG site
specifically. We previously developed a facile method for the site-specific
modification of full length, native IgGs by engineering a recombinant Protein Z
that forms a covalent link to the Fc domain of IgG upon exposure to long
wavelength UV light. To further improve the efficiency of Protein Z production
and IgG conjugation, we constructed a panel of 13 different Protein Z variants
with the UV-active amino acid benzoylphenylalanine (BPA) in different locations.
By using this panel of Protein Z to cross-link a range of IgGs from different
hosts, including human, mouse, and rat, we discovered two previously unknown
Protein Z variants, L17BPA and K35BPA, that are capable of cross-linking many
commonly used IgG isotypes with efficiencies ranging from 60% to 95% after only 1
h of UV exposure. When compared to existing site-specific methods, which often
require cloning or enzymatic reactions, the Protein Z-based method described
here, utilizing the L17BPA, K35BPA, and the previously described Q32BPA variants,
represents a vastly more accessible and efficient approach that is compatible
with nearly all native IgGs, thus making site-specific conjugation more
accessible to the general research community.
PMID- 25121622
TI - Activation of the D1 receptors inhibits the long-term potentiation in vivo
induced by acute morphine administration through a D1-GluN2A interaction in the
nucleus accumbens.
AB - Dopamine D1-like receptors can modulate glutamate-mediated excitatory synaptic
neurotransmission, but the underlying molecular mechanism remains elusive. Here,
we report that acute in-vivo morphine administration induces the long-term
potentiation (Mor-LTP) of field excitatory postsynaptic potentials at the
prefrontal cortex-to-nucleus accumbens shell synapses, and this process requires
the activation of GluN2A-containing N-methyl-D-aspartate receptors. This Mor-LTP
is completely inhibited by the D1-like receptor agonist SKF81297, but not by the
D2-like receptor agonist quinpirole. SKF81297-inhibited Mor-LTP is restored by
pretreatment with the TAT-conjugated interfering peptide TAT-D1-t3, which is a
synthetic blocker of the direct D1-GluN2A receptor interaction. These results
indicate that the activation of D1 receptors modulates Mor-LTP by the direct D1
GluN2A interaction at the prefrontal cortex-to-nucleus accumbens shell synapses
and might play a role in addiction-related plastic alterations.
PMID- 25121623
TI - Electrophysiological response to omitted stimulus in sentence processing.
AB - The current study provides evidence that the absence of a syntactically expected
item leads to a sustained cognitive processing demand. Event-related potentials
were measured at the omission of a syntactically expected object argument in a
speech sequence. English monolingual adults listened to paired sentences. The
first sentence in the pair established a context. The second sentence provided a
response to the first sentence that was either grammatically correct by
containing an overt object argument in the form of a pronoun, or was
syntactically unacceptable by omitting the expected object pronoun. Event-related
potentials measured at the omission of the object argument showed a prolonged
positivity for 100-600 ms with a broad scalp distribution, and for 600-1000 ms
with a focus in the anterior region. This observed omitted stimulus potential may
contain characteristics of the P300 component, associated with the detection of
the deviation of an expected stimulus, and the classical P600 related to
syntactic reanalysis. Further, the late anterior P600 may indicate an increased
memory demand in sentence comprehension. Thus, this linguistic omitted stimulus
potential is a cognitive indicator of language processing that can be used to
investigate the organization of linguistic knowledge.
PMID- 25121625
TI - Primary pure signet-ring cell carcinoma of the anus: a case report with
immunohistochemical study.
PMID- 25121624
TI - Acupuncture-induced changes in functional connectivity of the primary
somatosensory cortex varied with pathological stages of Bell's palsy.
AB - Bell's palsy is the most common cause of acute facial nerve paralysis. In China,
Bell's palsy is frequently treated with acupuncture. However, its efficacy and
underlying mechanism are still controversial. In this study, we used functional
MRI to investigate the effect of acupuncture on the functional connectivity of
the brain in Bell's palsy patients and healthy individuals. The patients were
further grouped according to disease duration and facial motor performance. The
results of resting-state functional MRI connectivity show that acupuncture
induces significant connectivity changes in the primary somatosensory region of
both early and late recovery groups, but no significant changes in either the
healthy control group or the recovered group. In the recovery group, the changes
also varied with regions and disease duration. Therefore, we propose that the
effect of acupuncture stimulation may depend on the functional connectivity
status of patients with Bell's palsy.
PMID- 25121626
TI - Signet-ring cell carcinoma of the nonampullary duodenum and proximal jejunum: a
case report with an immunohistochemical study.
PMID- 25121627
TI - Gastric gastrointestinal stromal tumor lost in the peritoneum after endoscopic
resection.
PMID- 25121628
TI - Doxycycline-induced pill esophagitis.
PMID- 25121629
TI - Large polypoid lymphoid follicles in the stomach causing anemia.
PMID- 25121631
TI - Endoscopic ultrasound-guided thrombin injection in a large splenic artery
aneurysm: first report in a patient with tropical chronic pancreatitis.
PMID- 25121632
TI - The "death" of lethal injection as we know it? The role of chemical execution in
the American criminal justice system.
AB - Several independent elements have recently combined to thrust United States
capital punishment into a chaos. Corrections officials and policy makers have
attempted to "humanize" capital punishment by evolving into a chemical execution
process, and soften the outward appearance. Foreign policies have interrupted
chemical protocols by banning key ingredients. These disruptions are spawning new
theories of legal challenges in capital punishment. This is a critical time for
stakeholders and all members of a civilized society to pause and reflect on the
role of capital punishment.
PMID- 25121630
TI - Extensive small-bowel Crohn's disease detected by the newly introduced 360
degrees panoramic viewing capsule endoscopy system.
PMID- 25121633
TI - An introduction to "keeping the 'health' in health communication": a column
devoted to interdisciplinary vocabulary.
AB - Health communication research and practice often involve interdisciplinary
collaborations. These endeavors include vocabularies associated with the
different disciplines and backgrounds of the collaborators. This feature will be
devoted to providing glossaries to introduce these vocabularies.
PMID- 25121634
TI - One-step synthesis of graphene-Au nanoparticle hybrid materials from metal salt
loaded micelles.
AB - In this study, we present a facile one-step method to synthesize graphene-Au
nanoparticle (NP) hybrid materials by using HAuCl4-loaded poly(styrene)-block
poly(2-vinylpyridine) (PS-P2VP) micelles as solid carbon sources. N-doped
graphene with controllable thickness can be grown from PS-P2VP micelles covered
by a Ni capping layer by an annealing process; simultaneously, the HAuCl4 in the
micelles were reduced into Au NPs under a reductive atmosphere to form Au NPs on
graphene. The decoration of Au NPs leads to an obviously enhanced electrical
conductivity and a slightly increased work function of graphene due to the
electron transfer effect. The graphene-Au NP hybrid materials also exhibit a
localized surface plasmon resonance feature of Au NPs. This work provides a novel
and accessible route for the one-step synthesis of graphene-Au NP hybrid
materials with high quality, which might be useful for future applications in
optoelectronic devices.
PMID- 25121635
TI - Rubus coreanus Miquel ameliorates scopolamine-induced memory impairments in ICR
mice.
AB - The present study investigated the effect of Rubus coreanus Miquel (RCM) on
scopolamine-induced memory impairments in ICR mice. Mice were orally
administrated RCM for 4 weeks and scopolamine was intraperitoneally injected into
mice to induce memory impairment. RCM improved the scopolamine-induced memory
impairment in mice. The increase of acetylcholinesterase activity caused by
scopolamine was significantly attenuated by RCM treatment. RCM increased the
levels of acetylcholine in the brain and serum of mice. The expression of choline
acetyltransferase, phospho-cyclic AMP response element-binding protein, and
phospho-extracellular signal-regulated kinase was significantly increased within
the brain of mice treated with RCM. The brain antioxidant enzyme activity
decreased by scopolamine was increased by RCM. These results demonstrate that RCM
exerts a memory-enhancing effect via the improvement of cholinergic function and
the potentiated antioxidant activity in memory-impaired mice. The results suggest
that RCM may be a useful agent for improving memory impairment.
PMID- 25121636
TI - Congenital hemophagocytic lymphohistiocytosis presenting as thrombocytopenia in a
newborn.
AB - Hemophagocytic lymphohistiocytosis (HLH) is a disease caused by dysregulation and
hyperactivation of the immune system, and can be familial or acquired. HLH
presenting in infancy can be rapidly fatal if not promptly recognized and
treated. Congenital HLH can be caused by various genetic mutations or part of
immunodeficiency syndromes. We present an infant with Griscelli syndrome and
familial HLH with atypical genetic mutations, presenting as thrombocytopenia on
the first day of life, cured with chemotherapy and unrelated cord blood
transplant.
PMID- 25121637
TI - Adjuvant Gemcitabine and Gemcitabine-based Chemoradiotherapy Versus Gemcitabine
Alone After Pancreatic Cancer Resection: The Indiana University Experience.
AB - OBJECTIVES: Adjuvant therapy after surgical resection is the current standard for
pancreatic adenocarcinoma; however, the role of chemoradiotherapy (CRT) remains
unclear. This study was conducted to compare the efficacy outcomes with adjuvant
gemcitabine and gemcitabine-based CRT (CT-CRT) versus gemcitabine chemotherapy
(CT) alone after pancreaticoduodenectomy. METHODS: Among 165 patients who
underwent surgical resection for pancreatic cancer at Indiana University Medical
Center between 2004 and 2008, we retrospectively identified 53 consecutive
patients who received adjuvant therapy (CT-CRT=34 patients; CT=19 patients) and
had adequate follow-up medical records. The median follow-up was 19.1 months.
Median disease-free (DFS) and overall survival (OS) were determined using Kaplan
Meier method, and a Cox-regression model was used to compare survival outcomes
after adjusting for age, status of resection margins, and lymph node involvement.
RESULTS: The OS for the CT-CRT group was significantly higher compared with the
CT group (median, 20.4 vs. 16.6 mo; hazard ratio, 2.42; 95% CI, 1.17-5.01). The
median DFS for the CT-CRT group was 13.7 versus 11.1 months for the CT group
(hazard ratio, 2.88; 95% CI, 1.37-6.06). On subgroup analyses, significantly
superior OS and DFS were observed among patients younger than 65 years, T3/T4
tumor stage, negative resection margins, and positive lymph node involvement.
CONCLUSION: Gemcitabine plus gemcitabine-based CRT compared with gemcitabine
alone leads to superior DFS and OS for patients with resected pancreatic cancer.
PMID- 25121638
TI - Competitive immunochromatographic assay for the detection of thiodiglycol
sulfoxide, a degradation product of sulfur mustard.
AB - An immunochromatographic assay (ICA) based on the competitive antigen-coated
format using colloidal gold as the label was developed for the detection of
thiodiglycol sulfoxide (TDGO), an important metabolite and degradation compound
of sulphur mustard (SM). The ICA test strip consisted of a membrane with a
detection zone, a sample pad and an absorbent pad. The membrane was separately
coated with hapten-OVA conjugate (test line) and anti-rabbit mouse IgG (control
line). The visual detection limit for TDGO by ICA detection was found to be 10
MUg mL(-1). For validation, the ICA results obtained for spiked water samples
were in good agreement with those obtained by indirect competitive inhibition
enzyme-linked immunosorbent assay (ELISA) for TDGO. The assay time for detection
was less than 10 min. The developed ICA has the potential to be a useful on-site
screening tool for the retrospective detection of SM in environmental samples.
PMID- 25121639
TI - Significance and costs of complex biopsychosocial health care needs in elderly
people: results of a population-based study.
AB - OBJECTIVE: To improve health care for the elderly, a consideration of
biopsychosocial health care needs may be of particular importance-especially
because of the prevalence of multiple conditions, mental disorders, and social
challenges facing elderly people. The aim of the study was to investigate
significance and costs of biopsychosocial health care needs in elderly people.
METHODS: Data were derived from the 8-year follow-up of the ESTHER study-a German
epidemiological study in the elderly population. A total of 3124 participants
aged 57 to 84 years were visited at home by trained medical doctors.
Biopsychosocial health care needs were assessed using the INTERMED for the
Elderly (IM-E) interview. Health-related quality of life (HRQOL) was measured by
the 12-Item Short-Form Health Survey, and psychosomatic burden was measured by
the Patient Health Questionnaire. RESULTS: The IM-E correlated with decreased
mental (mental component score: r = -0.38, p < .0001) and physical HRQOL
(physical component score: r = -0.45, p < .0001), increased depression severity
(r = 0.53, p < .0001), and costs (R = 0.41, p < .0001). The proportion of the
participants who had an IM-E score of at least 21 was 8.2%; according to previous
studies, they were classified as complex patients (having complex biopsychosocial
health care needs). Complex patients showed a highly reduced HRQOL compared with
participants without complex health care needs (mental component score: 37.0
[10.8] versus 48.7 [8.8]; physical component score: 33.0 [9.1] versus 41.6
[9.5]). Mean health care costs per 3 months of complex patients were strongly
increased (1651.1 &OV0556; [3192.2] versus 764.5 &OV0556; [1868.4]). CONCLUSIONS:
Complex biopsychosocial health care needs are strongly associated with adverse
health outcomes in elderly people. It should be evaluated if interdisciplinary
treatment plans would improve the health outcomes for complex patients.
PMID- 25121640
TI - Quantitative Trait Loci from Two Genotypes of Oat (Avena sativa) Conditioning
Resistance to Puccinia coronata.
AB - Developing oat cultivars with partial resistance to crown rust would be
beneficial and cost-effective for disease management. Two recombinant inbred-line
populations were generated by crossing the susceptible cultivar Provena with two
partially resistant sources, CDC Boyer and breeding line 94197A1-9-2-2-2-5. A
third mapping population was generated by crossing the partially resistant
sources to validate the quantitative trait locus (QTL) results. The three
populations were evaluated for crown rust severity in the field at Louisiana
State University (LSU) in 2009 and 2010 and at the Cereal Disease Laboratory
(CDL) in St. Paul, MN, in 2009, 2010, and 2011. An iSelect platform assay
containing 5,744 oat single nucleotide polymorphisms was used to genotype the
populations. From the 2009 CDL test, linkage analyses revealed two QTLs for
partial resistance in the Provena/CDC Boyer population on chromosome 19A. One of
the 19A QTLs was also detected in the 2009 LSU test. Another QTL was detected on
chromosome 12D in the CDL 2009 test. In the Provena/94197A1-9-2-2-2-5 population,
only one QTL was detected, on chromosome 13A, in the CDL 2011 test. The 13A QTL
from the Provena/94197A1-9-2-2-2-5 population was validated in the CDC
Boyer/94197A1-9-2-2-2-5 population in the CDL 2010 and 2011 tests. Comparative
analysis of the significant marker sequences with the rice genome database
revealed 15 candidate genes for disease resistance on chromosomes 4 and 6 of
rice. These genes could be potential targets for cloning from the two resistant
parents.
PMID- 25121641
TI - Regional and field-specific factors affect the composition of fusarium head
blight pathogens in subtropical no-till wheat agroecosystem of Brazil.
AB - A multiyear survey of >200 wheat fields in Parana (PR) and Rio Grande do Sul (RS)
states was conducted to assess the extent and distribution of Fusarium
graminearum species complex (FGSC) diversity in the southern Brazilian wheat
agroecosystem. Five species and three trichothecene genotypes were found among
671 FGSC isolates from Fusarium head blight (FHB)-infected wheat heads: F.
graminearum (83%) of the 15-acetyldeoxynivalenol (15-ADON) genotype, F.
meridionale (12.8%) and F. asiaticum (0.4%) of the nivalenol (NIV) genotype, and
F. cortaderiae (2.5%) and F. austroamericanum (0.9%) with either the NIV or the 3
ADON genotype. Regional differences in FGSC composition were observed, with F.
meridionale and the NIV type being significantly (P<0.001) more prevalent in PR
(>28%) than in RS (<=9%). Within RS, F. graminearum was overrepresented in fields
below 600 m in elevation and in fields with higher levels of FHB incidence
(P<0.05). Species composition was not significantly influenced by previous crop
or the stage of grain development at sampling. Habitat-specific differences in
FGSC composition were evaluated in three fields by characterizing a total of 189
isolates collected from corn stubble, air above the wheat canopy, and symptomatic
wheat kernels. Significant differences in FGSC composition were observed among
these habitats (P<0.001). Most strikingly, F. meridionale and F. cortaderiae of
the NIV genotype accounted for the vast majority (>96%) of isolates from corn
stubble, whereas F. graminearum with the 15-ADON genotype was dominant (>84%)
among isolates from diseased wheat kernels. Potential differences in pathogenic
fitness on wheat were also suggested by a greenhouse competitiveness assay in
which F. graminearum was recovered at much higher frequency (>90%) than F.
meridionale from four wheat varieties inoculated with an equal mixture of F.
graminearum and F. meridionale isolates. Taken together, the data presented here
suggest that FGSC composition and, consequently, the trichothecene contamination
in wheat grown in southern Brazil is influenced by host adaptation and pathogenic
fitness. Evidence that F. meridionale and F. cortaderiae with the NIV genotype
are regionally significant contributors to FHB may have significant implications
for food safety and the economics of cereal production.
PMID- 25121642
TI - Evidence for Systemic Infection by Puccinia horiana, Causal Agent of
Chrysanthemum White Rust, in Chrysanthemum.
AB - Puccinia horiana, causal agent of the disease commonly known as chrysanthemum
white rust (CWR), is a quarantine-significant fungal pathogen of chrysanthemum in
the United States and indigenous to Asia. The pathogen was believed to have been
eradicated in the United States but recently reappeared on several occasions in
northeastern United States. The objective of the study presented here was to
determine whether P. horiana could systemically infect chrysanthemum plants, thus
providing a means of survival through winters. Scanning and transmission electron
microscopy revealed the development of P. horiana on the surface and within
leaves, stems, or crowns of inoculated chrysanthemum plants artificially exposed
to northeastern U.S. winter temperatures. P. horiana penetrated leaves directly
through the cuticle and then colonized the mesophyll tissue both inter- and
intracellularly. An electron-dense material formed at the interface between
fungal and host mesophyll cells, suggesting that the pathogen adhered to the
plant cells. P. horiana appeared to penetrate mesophyll cell walls by enzymatic
digestion, as indicated by the absence of deformation lines in host cell walls at
penetration sites. The fungus was common in vascular tissue within the infected
crown, often nearly replacing the entire contents of tracheid cell walls. P.
horiana frequently passed from one tracheid cell to an adjacent tracheid cell by
penetration either through pit pairs or nonpitted areas of the cell walls.
Individual, presumed, fungal cells in mature tracheid cells of the crown and
stems arising from infected crowns suggested that the pathogen might have been
moving at least partially by means of the transpiration stream. The demonstration
that chrysanthemum plants can be systemically infected by P. horiana suggests
that additional disease control measures are required to effectively control CWR.
PMID- 25121644
TI - Ab initio chemical synthesis of designer metal phosphate frameworks at ambient
conditions.
AB - Stepwise hierarchical and rational synthesis of porous zinc phosphate frameworks
by predictable and directed assembly of easily isolable tetrameric zinc phosphate
[Zn(dipp)(solv)]4 (dippH2 = diisopropylphenyldihydrogen phosphate; solv = CH3OH
or dimethyl sulfoxide) with D4R (double-4-ring) topology has been achieved. The
preformed and highly robust D4R secondary building unit can be coordinatively
interconnected through a varied choice of bipyridine-based ditopic spacers L1-L7
to isolate eight functional zinc phosphate frameworks,
[Zn4(dipp)4(L1)1.5(DMSO)].4H2O (2), [Zn4(dipp)4(L2)1.5(CH3OH)] (3),
[Zn4(dipp)4(L1)2] (4), [Zn4(dipp)4(L3)2] (5), [Zn4(dipp)4(L4)2] (6),
[Zn4(dipp)4(L5)2] (7), [Zn4(dipp)4(L6)2] (8), and [Zn4(dipp)4(L7)2] (9), in good
yield. The preparative procedures are simple and do not require high pressure or
temperature. Surface area measurements of these framework solids show that the
guest accessibility of the frameworks can be tuned by suitable modification of
bipyridine spacers.
PMID- 25121643
TI - Sodium dodecyl sulfate monomers induce XAO peptide polyproline II to alpha-helix
transition.
AB - XAO peptide (Ac-X2A7O2-NH2; X: diaminobutyric acid side chain, -CH2CH2NH3(+); O:
ornithine side chain, -CH2CH2CH2NH3(+)) in aqueous solution shows a predominantly
polyproline II (PPII) conformation without any detectable alpha-helix-like
conformations. Here we demonstrate by using circular dichroism (CD), ultraviolet
resonance Raman (UVRR) and nuclear magnetic resonance (NMR) spectroscopy that
sodium dodecyl sulfate (SDS) monomers bind to XAO and induce formation of alpha
helix-like conformations. The stoichiometry and the association constants of SDS
and XAO were determined from the XAO-SDS diffusion coefficients measured by
pulsed field gradient NMR. We developed a model for the formation of XAO-SDS
aggregate alpha-helix-like conformations. Using UVRR spectroscopy, we calculated
the Ramachandran psi angle distributions of aggregated XAO peptides. We resolved
alpha-, pi- and 3(10)-helical conformations and a turn conformation. XAO
nucleates SDS aggregation at SDS concentrations below the SDS critical micelle
concentration. The XAO4-SDS16 aggregates have four SDS molecules bound to each
XAO to neutralize the four side chain cationic charges. We propose that the SDS
alkyl chains partition into a hydrophobic core to minimize the hydrophobic area
exposed to water. Neutralization of the flanking XAO charges enables alpha-helix
formation. Four XAO-SDS4 aggregates form a complex with an SDS alkyl chain
dominated hydrophobic core and a more hydrophilic shell where one face of the
alpha-helix peptide contacts the water environment.
PMID- 25121646
TI - Determining asymptotically large population sizes in insect swarms.
AB - Social animals commonly form aggregates that exhibit emergent collective
behaviour, with group dynamics that are distinct from the behaviour of
individuals. Simple models can qualitatively reproduce such behaviour, but only
with large numbers of individuals. But how rapidly do the collective properties
of animal aggregations in nature emerge with group size? Here, we study swarms of
Chironomus riparius midges and measure how their statistical properties change as
a function of the number of participating individuals. Once the swarms contain
order 10 individuals, we find that all statistics saturate and the swarms enter
an asymptotic regime. The influence of environmental cues on the swarm morphology
decays on a similar scale. Our results provide a strong constraint on how rapidly
swarm models must produce collective states. But our findings support the
feasibility of using swarms as a design template for multi-agent systems, because
self-organized states are possible even with few agents.
PMID- 25121645
TI - Physical activity, sedentary behavior and risk of hypertensive disorders of
pregnancy in Hispanic women.
AB - OBJECTIVE: Prior studies of the association between physical activity and
hypertensive disorders of pregnancy have been conflicting; the majority focused
on leisure-time activity only, did not use physical activity questionnaires
validated for pregnancy, and were conducted in primarily non-Hispanic white
populations. METHODS: We prospectively evaluated this association among 1240
Hispanic women in Proyecto Buena Salud. The Pregnancy Physical Activity
Questionnaire, validated for use in pregnancy, was used to assess pre- and early
pregnancy sports/exercise, household/caregiving, occupational and transportation
activity. Diagnoses of hypertensive disorders of pregnancy were based on medical
record abstraction and confirmed by the study obstetrician. RESULTS: A total of
49 women (4.0%) were diagnosed with a hypertensive disorder of pregnancy,
including 32 women (2.6%) with pre-eclampsia. In age-adjusted analyses, high
levels of early pregnancy household/caregiving activity were associated with
reduced risk of total hypertensive disorders (OR = 0.4, 95% CI 0.1-0.9) and pre
eclampsia (OR = 0.3, 95% CI 0.1-0.9) relative to low levels; however, these
findings were no longer statistically significant in multivariable models. Pre
pregnancy activity and pattern of activity from pre- to early-pregnancy were not
significantly associated with risk. Finally, sedentary behavior was not
significantly associated with hypertensive disorders. CONCLUSION: Findings from
this prospective study of Hispanic women were consistent with those of prior
prospective cohorts indicating that physical activity prior to and during early
pregnancy does not significantly reduce risk of hypertensive disorders of
pregnancy.
PMID- 25121647
TI - Programming chemistry in DNA-addressable bioreactors.
AB - We present a formal calculus, termed the chemtainer calculus, able to capture the
complexity of compartmentalized reaction systems such as populations of possibly
nested vesicular compartments. Compartments contain molecular cargo as well as
surface markers in the form of DNA single strands. These markers serve as
compartment addresses and allow for their targeted transport and fusion, thereby
enabling reactions of previously separated chemicals. The overall system
organization allows for the set-up of programmable chemistry in microfluidic or
other automated environments. We introduce a simple sequential programming
language whose instructions are motivated by state-of-the-art microfluidic
technology. Our approach integrates electronic control, chemical computing and
material production in a unified formal framework that is able to mimic the
integrated computational and constructive capabilities of the subcellular matrix.
We provide a non-deterministic semantics of our programming language that enables
us to analytically derive the computational and constructive power of our
machinery. This semantics is used to derive the sets of all constructable
chemicals and supermolecular structures that emerge from different underlying
instruction sets. Because our proofs are constructive, they can be used to
automatically infer control programs for the construction of target structures
from a limited set of resource molecules. Finally, we present an example of our
framework from the area of oligosaccharide synthesis.
PMID- 25121648
TI - Interfacial and biological properties of the gradient coating on polyamide
substrate for bone substitute.
AB - Fabrication of bioactive and mechanical matched bone substitutes is crucial for
clinical application in bone defects repair. In this study, nano
hydroxyapatite/polyamide (nHA/PA) composite was coated on injection-moulded PA by
a chemical corrosion and phase-inversion technique. The shear strength, gradient
composition and pore structure of the bioactive coating were characterized.
Osteoblast-like MG63 cells were cultured on pure PA and composite-coated PA
samples. The cells' adhesion, spread and proliferation were determined using MTT
assay and microscopy. The results confirm that the samples with the nHA/PA
composite coating have better cytocompatibility and have no negative effects on
cells. To investigate the in vivo biocompatibility, both pure PA and composite
coated PA cylinders were implanted in the trochlea of rabbit femurs and studied
histologically, and the bonding ability with bone were determined using push-out
tests. The results show that composite-coated implants exhibit better
biocompatibility and the shear strength of the composite-coated implants with
host bone at 12 weeks can reach 3.49+/-0.42 MPa, which is significantly higher
than that of pure PA implants. These results indicate that composite-coated PA
implants have excellent biocompatibility and bonding abilities with host bone and
they have the potential to be applied in repair of bone defects.
PMID- 25121652
TI - Polarization-sensitive OFDI using polarization-multiplexed wavelength-swept
laser.
AB - We demonstrate a novel polarization-sensitive optical frequency domain imaging
system employing passive polarization multiplexing. Simple modification of a
fiber delay line in the wavelength-swept light source enables illumination with
two perpendicular polarizations that are required for determination of the Stokes
vector components of the light reflected from each depth of the tissue. This
simple all-passive approach provides a robust and low-cost solution for PS
imaging replacing relatively complex conventional schemes such as polarization
modulation or frequency-encoded polarization multiplexing.
PMID- 25121651
TI - Real-time optoacoustic tomography of indocyanine green perfusion and oxygenation
parameters in human finger vasculature.
AB - We interrogated whether optoacoustic tomography could be employed to study blood
functional parameters and biodistribution of injected fluorescent agents in
humans. Using a multichannel scanner at a frame rate of 10 images per second, we
obtained cross-sectional images of the human finger in real time, before and
after the administration of indocyanine green. We demonstrated that multispectral
optoacoustic tomography can sense fast flow kinetics and resolve spatiotemporal
characteristics of a common fluorochrome in human vasculature at clinically
relevant concentrations. We further register ICG images with oxygen saturation
maps and anatomical views of the proximal interphalangeal joint of a healthy
volunteer.
PMID- 25121653
TI - Broadband angular filtering with a volume Bragg grating and a surface grating
pair.
AB - We propose and perform broadband angular filtering with the combination of a
volume Bragg grating and a surface grating pair. The condition for broadband
operation is discussed. Near-field modulation, contrast ratio, and power spectral
density are used to evaluate the filtering performances in the spatial and
frequency domain. Experimental results show that the bandwidth of the output beam
through the grating combination is remarkably increased, and the medium and high
frequencies are effectively eliminated.
PMID- 25121650
TI - Masticatory biomechanics in the rabbit: a multi-body dynamics analysis.
AB - Multi-body dynamics is a powerful engineering tool which is becoming increasingly
popular for the simulation and analysis of skull biomechanics. This paper
presents the first application of multi-body dynamics to analyse the biomechanics
of the rabbit skull. A model has been constructed through the combination of
manual dissection and three-dimensional imaging techniques (magnetic resonance
imaging and micro-computed tomography). Individual muscles are represented with
multiple layers, thus more accurately modelling muscle fibres with complex lines
of action. Model validity was sought through comparing experimentally measured
maximum incisor bite forces with those predicted by the model. Simulations of
molar biting highlighted the ability of the masticatory system to alter
recruitment of two muscle groups, in order to generate shearing or crushing
movements. Molar shearing is capable of processing a food bolus in all three
orthogonal directions, whereas molar crushing and incisor biting are
predominately directed vertically. Simulations also show that the masticatory
system is adapted to process foods through several cycles with low muscle
activations, presumably in order to prevent rapidly fatiguing fast fibres during
repeated chewing cycles. Our study demonstrates the usefulness of a validated
multi-body dynamics model for investigating feeding biomechanics in the rabbit,
and shows the potential for complementing and eventually reducing in vivo
experiments.
PMID- 25121649
TI - An explicit immunogenetic model of gastrointestinal nematode infection in sheep.
AB - Gastrointestinal nematodes are a global cause of disease and death in humans,
wildlife and livestock. Livestock infection has historically been controlled with
anthelmintic drugs, but the development of resistance means that alternative
controls are needed. The most promising alternatives are vaccination, nutritional
supplementation and selective breeding, all of which act by enhancing the immune
response. Currently, control planning is hampered by reliance on the faecal egg
count (FEC), which suffers from low accuracy and a nonlinear and indirect
relationship with infection intensity and host immune responses. We address this
gap by using extensive parasitological, immunological and genetic data on the
sheep-Teladorsagia circumcincta interaction to create an immunologically explicit
model of infection dynamics in a sheep flock that links host genetic variation
with variation in the two key immune responses to predict the observed
parasitological measures. Using our model, we show that the immune responses are
highly heritable and by comparing selective breeding based on low FECs versus
high plasma IgA responses, we show that the immune markers are a much improved
measure of host resistance. In summary, we have created a model of host-parasite
infections that explicitly captures the development of the adaptive immune
response and show that by integrating genetic, immunological and parasitological
understanding we can identify new immune-based markers for diagnosis and control.
PMID- 25121654
TI - Direct comparison of optical lattice clocks with an intercontinental baseline of
9000 km.
AB - We have demonstrated a direct frequency comparison between two 87Sr lattice
clocks operated in intercontinentally separated laboratories in real time. Two
way satellite time and frequency transfer technique, based on the carrier-phase,
was employed for a direct comparison, with a baseline of 9000 km between Japan
and Germany. A frequency comparison was achieved for 83,640 s, resulting in a
fractional difference of (1.1+/-1.6)*10-15, where the statistical part is the
largest contributor to the uncertainty. This measurement directly confirms the
agreement of the two optical frequency standards on an intercontinental scale.
PMID- 25121655
TI - Polarization-resolved near-backscattering of airborne aggregates composed of
different primary particles.
AB - We measured the polarization-resolved angular elastic scattering intensity
distribution of aggregates composed of primary particles with different shapes
and packing densities in the near-backward directions (155 degrees -180 degrees
). Specifically, we compare aggregates composed of spherical polystyrene latex
spheres, cylinder-like Bacillus subtilis particles, and Arizona road dust, as
well as tryptophan particles. We observe clearly differentiable polarization
aspect ratios and find that the negative polarization dip is more pronounced in
more densely packed aggregates or particles. This work indicates that the
polarization aspect ratio in the near-backward direction may be used as a
fingerprint to discriminate between aggregates with the same size and overall
shape by differences in their constituent particles.
PMID- 25121656
TI - Phase-predictable tuning of single-frequency optical synthesizers.
AB - We investigate the tuning behavior of a novel type of single-frequency optical
synthesizers by phase comparison of the output signals of two identical devices.
We achieve phase-stable and cycle-slip free frequency tuning over 28.1 GHz with a
maximum zero-to-peak phase deviation of 62 mrad. In contrast to previous
implementations of single-frequency optical synthesizers, no comb line order
switching is needed when tuned over more than one comb line spacing range of the
employed frequency comb.
PMID- 25121657
TI - Control of chromaticity by phosphor in glasses with low temperature sintered
silicate glasses for LED applications.
AB - Phosphor-in-glass (PiG) color converters for LED applications were fabricated
with a mixture of phosphors, Y3Al5O12:Ce3+ (yellow) and CaAlSiN3:Eu2+ (red). The
low sintering temperature (550 degrees C) of SiO2-Na2O-RO (R=Ba, Zn) glass powder
enabled the inclusion of CaAlSiN3:Eu2+ (red) phosphor which cannot be embedded
with conventional glass powders for PiGs. By simply varying the mixing ratio of
glass to phosphors as well as the ratio of yellow to red phosphors, the facile
control of the CIE chromaticity coordinates and correlated color temperature of
the LED following the Planckian locus has been achieved. Phosphors were well
distributed within the glass matrix without noticeable reactions, preserving the
enhanced thermal quenching property of the PiG compared to those with silicone
resins, for LEDs.
PMID- 25121658
TI - Plasmon mode characteristics of metallic nanowire in uniaxial anisotropic
dielectric.
AB - The plasmon mode characteristics of metallic nanowire embedded in a uniaxial
anisotropic dielectric are investigated theoretically. The hybrid plasmon modes
found in this structure are significantly different from the traditional plasmon
modes of metallic nanowire in a homogeneous isotropic dielectric. In contrast to
the transverse-magnetic-like wave for a traditional fundamental mode, the hybrid
fundamental mode of metallic nanowire involves a nonzero longitudinal magnetic
field component. The degenerate behaviors of adjacent order plasmon modes are
demonstrated in the case of a strongly anisotropic dielectric. Moreover, the
dependence of the degenerate characteristics on the radius of a metallic nanowire
and the excited wavelength are clearly shown by dispersion relation. The results
of the study provide a useful approach to modulate surface plasmon polaritons
with anisotropic medium.
PMID- 25121659
TI - Possibility of direct estimation of terahertz pulse electric field.
AB - In this Letter, we introduce a new method of estimation of the terahertz (THz)
field amplitude. This method uses second-harmonic generation (SHG) in the
presence of THz and DC fields in gaseous media. We take into account
contributions from both nonionized molecules and free plasma electrons to the
nonlinear process of SHG. We analyze the applicability of this method of
detection to obtaining correct information on the waveform and amplitude of
broadband THz pulses.
PMID- 25121660
TI - Polarization-dependent study of THz air-biased coherent detection.
AB - We present an investigation of the polarization dependence of THz air-biased
coherent detection (ABCD) on the polarization directions of fundamental waves.
The intensity, ellipticity, and polarization angle of the THz-field-induced
second-harmonic are affected by the air plasma birefringence and can be predicted
by cross-phase modulation theory. Due to the plasma birefringence, the
polarization state of THz waves cannot be determined by the polarization state of
the second harmonic with the traditional polarization measurement method. It
would be inaccurate to measure arbitrary THz-wave polarization in a single scan
with THz ABCD when the birefringence effect is significant.
PMID- 25121661
TI - Giant Goos-Hanchen shift in scattering: the role of interfering localized plasmon
modes.
AB - The longitudinal and transverse beam shifts, namely, the Goos-Hanchen (GH) and
the Spin-Hall (SH) shifts are usually observed at planar interfaces. It has
recently been shown that the transverse SH shift may also arise due to scattering
of plane waves. Here, we show that analogous in-plane (longitudinal) shifts also
exist in the scattering of plane waves from micro/nano systems. We study both the
GH and the SH shifts in plasmonic metal nanoparticles/nanostructures and
dielectric micro-particles employing a unified framework that utilizes the
transverse components of the Poynting vector of the scattered wave. The results
demonstrate that the interference of neighboring resonance modes in plasmonic
nanostructures (e.g., electric dipolar and quadrupolar modes in metal spheres)
leads to great enhancement of the GH shift in scattering from such systems. We
also unravel interesting correlations between these shifts with the polarimetry
parameters, diattenuation and retardance.
PMID- 25121662
TI - Rigorous speckle simulation using surface integral equations and higher order
boundary element method.
AB - The scattering of electromagnetic waves from rough surfaces has been actively
studied for more than a century now because of its involvement in vast
application areas. In the past two decades, great advances have been made by
incorporating multiple scattering effects into analytical approaches. However, no
model can yet be applied to surfaces with arbitrary roughness. It is also very
difficult to study the cross-polarization, shadowing, or multiple scattering
effects. In order to study more fundamentally the interaction of polarized light
with more general rough surfaces of general media, we have developed a rigorous
numerical simulator to calculate the resulting speckle fields. The full Maxwell
equations were solved using surface integral equations combined with a boundary
element method. The rough surface was discretized by higher order quadrilateral
edge elements. The effective tangential electric and magnetic fields in each
element in terms of 10 edges were first solved. The scattered electric and
magnetic fields everywhere in space were then calculated correspondingly. One of
the great advantages of such a simulator is that both the near and far fields can
be calculated directly. Preliminary results of different kinds of metallic
structures are presented, by which the advantages of the method are demonstrated.
PMID- 25121663
TI - Surface plasmons in nanowires with toroidal magnetic structure.
AB - We consider the problem of the influence of a toroidal magnetization on a
cylindrical surface plasmon polariton (SPP) propagating along a nanowire of a
circular cross section. It follows from the dispersion equations that the SPP
wavenumber linearly depends on the toroidal moment and the effect of magneto
optical nonreciprocity appears. The numerical solution of the dispersion
equations demonstrates that the corresponding splitting of the SPP dispersion
curves for two opposite directions of the toroidal moment is increased by an
order of magnitude with respect to the planar case. The largest values of this
splitting are observed for systems with relatively low optical losses, as is
demonstrated by calculations for SPPs in a gold cylinder surrounded by rare-earth
bismuth iron garnet.
PMID- 25121664
TI - Sub-10-fs pulses tunable from 480 to 980 nm from a NOPA pumped by an Yb:KGW
source.
AB - We describe two noncollinear optical parametric amplifier (NOPA) systems pumped
by either the second (515 nm) or the third (343 nm) harmonic from an Yb:KGW
source. Pulse durations as short as 6.8 fs are readily obtained by compression
with chirped mirrors. The availability of both the second and third harmonics for
NOPA pumping allows for gap-free tuning from 520 to 980 nm. The use of an
intermediate NOPA to generate seed light at 780 nm extends the tuning range of
the third harmonic pumped NOPA toward 450 nm.
PMID- 25121665
TI - Flexible operability and amplification of gray pulses.
AB - We have investigated experimentally the flexible production and amplification of
gray pulses for the first time to our knowledge. Switchable wavelengths, tunable
pulse-widths, and adjustable contrasts have all been obtained in a fiber laser.
Amplification of gray pulses was also experimentally investigated in detail. The
contrast of the pulses could also be increased in an amplifier. The robust
stability that results from the interactions between adjacent harmonic mode
locking counterparts of gray pulses was found to last for up to ten hours. To the
best of our knowledge, the gray pulses trains we have generated are the most
stable achieved to date in an all-fiber laser system. This finding can be used as
a guide for the establishment of robust gray pulses as laser sources.
PMID- 25121666
TI - Ultralong photonic nanojet formed by a two-layer dielectric microsphere.
AB - A photonic nanojet is a highly focused optical beam with a subwavelength waist on
the shadow side of the sphere. Successful far-field applications require long
nanojets that extend afar. Using the exact Mie theory, we show that ultralong
nanojets can be generated using a simple two-layer microsphere structure, using
conventional optical materials that are readily available. In particular, we show
that for a glass-based two-layer microsphere, the nanojet has an extension of 22
wavelengths. We also show that long nanojets can be formed using semiconductors
at infrared frequencies in free space.
PMID- 25121667
TI - Time-resolved coherent Raman spectroscopy by high-speed pump-probe delay
scanning.
AB - Using a spinning window pump-probe delay scanner, we demonstrate a means of
acquiring time-resolved vibrational spectra at rates up to 700 Hz. The time
dependent phase shift accumulated by the probe pulse in the presence of a
coherently vibrating sample gives rise to a Raman-induced frequency shifting
readily detectable in a balanced detector. This rapid delay scanning system
represents a 23-fold increase in averaging speed and is >10* faster than state-of
the-art voice coil delay lines. These advancements make pump-probe spectroscopy a
more practical means of imaging complex media.
PMID- 25121668
TI - Nanoscale TiO2-coated LPGs as radiation-tolerant humidity sensors for high-energy
physics applications.
AB - This Letter deals with a feasibility analysis for the development of radiation
tolerant fiber-optic humidity sensors based on long-period grating (LPG)
technology to be applied in high-energy physics (HEP) experiments currently
running at the European Organization for Nuclear Research (CERN). In particular,
here we propose a high-sensitivity LPG sensor coated with a finely tuned titanium
dioxide (TiO2) thin layer (~100 nm thick) through the solgel deposition method.
Relative humidity (RH) monitoring in the range 0%-75% and at four different
temperatures (in the range -10 degrees C-25 degrees C) was carried out to assess
sensor performance in real operative conditions required in typical experiments
running at CERN. Experimental results demonstrate the very high RH sensitivities
of the proposed device (up to 1.4 nm/% RH in correspondence to very low humidity
levels), which turned out to be from one to three orders of magnitude higher than
those exhibited by fiber Bragg grating sensors coated with micrometer-thin
polyimide overlays. The radiation tolerance capability of the TiO2-coated LPG
sensor is also investigated by comparing the sensing performance before and after
its exposure to a 1 Mrad dose of gamma-ionizing radiation. Overall, the results
collected demonstrate the strong potential of the proposed technology with regard
to its future exploitation in HEP applications as a robust and valid alternative
to the commercial (polymer-based) hygrometers currently used.
PMID- 25121669
TI - Generation of 9 MeV gamma-rays by all-laser-driven Compton scattering with second
harmonic laser light.
AB - Gamma-ray photons with energy >9 MeV were produced when second-harmonic
generated laser light (3 eV) inverse-Compton-scattered from a counterpropagating
relativistic (~450 MeV) laser-wakefield-accelerated electron beam. Two laser
pulses from the same laser system were used: one to accelerate electrons and one
to scatter. Since the two pulses play very different roles in the gamma-ray
generation process, and thus have different requirements, a novel laser system
was developed. It separately and independently optimized the optical properties
of the two pulses. This approach also mitigated the deleterious effects on beam
focusing that generally accompany nonlinear optics at high peak-power levels.
PMID- 25121670
TI - Dark state lasers.
AB - We propose a new type of laser resonator based on imaginary energy-level
splitting (imaginary coupling or quality factor Q-splitting) in a pair of coupled
microcavities. A particularly advantageous arrangement involves two microring
cavities with different free-spectral ranges in a configuration wherein they are
coupled by far-field interference in a shared radiation channel. A novel Vernier
like effect for laser resonators is designed in which only one longitudinal
resonant mode has a lower loss than the small-signal gain and can achieve lasing
while all other modes are suppressed. This configuration enables ultrawidely
tunable single-frequency lasers based on either homogeneously or inhomogeneously
broadened gain media. The concept is an alternative to the common external cavity
configurations for achieving tunable single-mode operation in a laser. The
proposed laser concept builds on a high-Q "dark state," which is established by
radiative interference coupling and bears a direct analogy to parity-time
symmetric Hamiltonians in optical systems. Variants of this concept should be
extendable to parametric-gain-based oscillators, enabling widely tunable single
frequency light sources.
PMID- 25121671
TI - Enhanced XUV pulse generation at 89 nm via nonlinear interaction of UV
femtosecond filaments.
AB - We demonstrated efficient generation of ultrafast extreme ultraviolet (XUV)
pulses at 89 nm from an intense 267 nm UV femtosecond filamentation in argon gas.
The XUV pulse generation efficiency was significantly enhanced through UV
filament termination from the argon gas into the background vacuum that prevented
backconversion of the generated third-harmonic XUV to the fundamental-wave UV
pulses. This was further combined with noncollinear UV filament interaction that
produced volume-plasma to pre-extract XUV pulses from the filament core,
resulting in further XUV enhancement. The generated 89 nm XUV pulses reached what
is so far, to our knowledge, the highest pulse energy of 190 nJ.
PMID- 25121672
TI - Monolithically integrated selectable repetition-rate laser diode source of
picosecond optical pulses.
AB - We describe the characterization of a monolithically integrated photonic device
for short pulse generation featuring a mode-locked laser diode, a Mach-Zehnder
modulator (MZM), and a semiconductor optical amplifier (SOA). The integrated
device is designed for fabrication by a generic foundry scheme with a view to
ease of design, testing, and manufacture. Trains of 6.8 ps pulses are generated
at repetition rates that are electronically switchable from 14 GHz to 109 MHz.
The SOA boosts the peak power by 7.4 dB, and the pulses are compressible to 2.4
ps by dispersion compensation using single-mode telecommunications fiber.
PMID- 25121673
TI - Reweighted L1 regularization for restraining artifacts in FMT reconstruction
images with limited measurements.
AB - In fluorescence molecular tomography (FMT), many artifacts exist in the
reconstructed images because of the inherently ill-posed nature of the FMT
inverse problem, especially with limited measurements. A new method based on
iterative reweighted L1 (IRL1) regularization is proposed for reducing artifacts
with limited measurements. Phantom experiments demonstrate that the reconstructed
images have fewer artifacts even with very limited measurements. This indicates
that FMT based on IRL1 can obtain high-quality images and thus has the potential
to observe dynamic changes in fluorescence-targeted molecules.
PMID- 25121674
TI - Investigating diamond Raman lasers at the 100 W level using quasi-continuous-wave
pumping.
AB - Quasi-cw pumping is used to investigate the high-power characteristics of cw beam
conversion in diamond Raman lasers (DRLs). We show that thermal gradients
establish in DRLs at approximately 50 MUs for a 100 MUm pump beam diameter, and
thus that the steady state for cw operation can be reached within the 100-300 MUs
pulse duration of conventional quasi-cw pump laser technology. Using this
approach, a steady-state on-time output power of 108 W was obtained from an
external-cavity DRL during 250 MUs pulses with 34% conversion efficiency. No
thermal lens in the diamond was evident, showing excellent prospects for further
power scaling.
PMID- 25121676
TI - Multiwavelength phase unwrapping and aberration correction using depth filtered
digital holography.
AB - In this Letter, we present a new approach to processing data from a standard
spectral domain optical coherence tomography (OCT) system using depth filtered
digital holography (DFDH). Intensity-based OCT processing has an axial resolution
of the order of a few micrometers. When the phase information is used to obtain
optical path length differences, subwavelength accuracy can be achieved, but this
limits the resolvable step heights to half of the wavelength of the system. Thus
there is a metrology gap between phase- and intensity-based methods. Our concept
addresses this metrology gap by combining DFHD with multiwavelength phase
unwrapping. Additionally, the measurements are corrected for aberrations. Here,
we present proof of concept measurements of a structured semiconductor sample.
PMID- 25121675
TI - L(p) regularization for early gate fluorescence molecular tomography.
AB - Time domain fluorescence molecular tomography (TD-FMT) provides a unique dataset
for enhanced quantification and spatial resolution. The time-gate dataset can be
divided into two temporal groups around the maximum counts gate, which are early
gates and late gates. It is well established that early gates allow for improved
spatial resolution and late gates are essential for fluorophore unmixing and
concentration quantification. However, the inverse problem of FMT is ill-posed
and typically underdetermined, which makes image reconstruction highly
susceptible to data noise. More specifically, photon counts are inherently very
low at early gates due to high absorption and scattering of tissue, resulting in
a low signal-to-noise ratio and unstable reconstructions. In this work, an L(p)
regularization-based reconstruction algorithm was developed and tested with our
wide-field mesh-based Monte Carlo simulation strategy. We compared the early time
gate reconstructions obtained with the different p (p?{1/16,1/8,1/4,1/3,1/2,1,2})
from a synthetic murine model simulating the fluorophore uptake in the kidneys
and preclinical data. The results from a 3D mouse atlas and a mouse experiment
show that our L(1/4) regularization methods give the best performance for early
time gates reconstructions.
PMID- 25121677
TI - Excellent optical thermometry based on single-color fluorescence in spherical
NaEuF4 phosphor.
AB - Temperature-dependent luminescence of spherical NaEuF4 phosphors with different
particle sizes was studied. The thermally coupled 5D0 and 5D1 level of Eu3+ was
observed. The linear dependence of emission intensities of 5D0 level of NaEuF4
phosphor on temperature confirmed the excellent temperature sensing performance.
Sensitivity up to 0.43% is achieved via decreasing the particle size, which is
higher than that of reported thermometry based on upconversion of lanthanide
ions. Moreover, the original luminescent intensity of 90% was recovered after 10
temperature-changed cycles, indicating good sensing stability. Therefore,
spherical NaEuF4 phosphor might be a promising candidate for optical temperature
sensors.
PMID- 25121678
TI - Ultrahigh-capacity access network architecture for mobile data backhaul using
integrated W-band wireless and free-space optical links with OAM multiplexing.
AB - In this Letter, we propose and experimentally demonstrate a novel access network
architecture using hybrid integrated W-band wireless and free-space optical (FSO)
links with orbital angular momentum (OAM) multiplexing. The transmission of a 20
GBd quadrature phase-shift keying signal modulated over 10 OAM modes has been
demonstrated over a 0.6 m FSO link and a 0.4 m W-band wireless link at 100 GHz.
The experimental results show that the architecture can support future ultrahigh
capacity, converged optical-wireless access networks that require extra bandwidth
and system flexibility in mobile data networks.
PMID- 25121679
TI - Surface and thickness profile measurement of a transparent film by three
wavelength vertical scanning interferometry.
AB - We have developed a novel areal film thickness and topography measurement method
using three-wavelength interferometry. The method simultaneously estimates the
profiles of the front and back surfaces and the thickness distribution of a
transparent film by model-based separation of two overlapped signals in an
interferogram. The validity of the proposed method is demonstrated using computer
simulations and actual experiments.
PMID- 25121680
TI - Edge extraction using a time-varying vortex beam in incoherent digital
holography.
AB - Edge extraction using a time-varying vortex beam (TV-VB) is demonstrated in
optical scanning holography (OSH) operating in an incoherent mode. OSH is a two
pupil heterodyne scanning optical system. We propose that one of the pupil
functions used is a delta function and the other pupil function is a spiral phase
plate (SPP). The interference of these pupils creates a TV-VB to scan over an
object to record the edge-only information of an object holographically. We also
find that a reconstructed edge with better contrast is achieved by translating
the SPP away from the pupil plane. Experimental results are compared with
computer simulations and found to be in good agreement.
PMID- 25121681
TI - Optomechanically induced transparency in the mechanical-mode splitting regime.
AB - We employ a decoupled Heisenberg-Langevin equation for the observation and
physical interpretation of mechanical-mode splitting (MMS) of the movable mirror
in a generic optomechanical system. Then we identify some observable and
significant features of MMS in a two-mode cavity. That is, the second control
field coupled to another optical mode is input to the system to modify the
mechanical mode, leading to the suppression of transmission, the appearance of
the doublet in the spectrum of the anti-Stokes field, and the emergence of
optomechanically induced transparency in corresponding new mechanical modes.
Furthermore, we open two transparent windows in virtue of MMS and find the second
splitting of the mechanical mode in this two-mode optomechanical system.
PMID- 25121683
TI - Two types of sinc Schell-model beams and their propagation characteristics.
AB - Two types of partially coherent beams with sinc Schell-model-correlated function
are introduced. The evolution behaviors of scalar beams generated by these two
types of sources in free space are investigated with the help of the weighted
superposition method and numerical examples. It is illustrated that the far field
produced by these two novel sources carry tunable flat and dark hollow profiles,
respectively. Our results suggest two new kinds of modal structure of the
correlation source and of the optical field that such sources produce.
PMID- 25121682
TI - Si/ZnO nanocomb arrays decorated with Ag nanoparticles for highly efficient
surface-enhanced Raman scattering.
AB - High-density ZnO nanocombs were first grown on a nanoporous silicon pillar array,
and pre-prepared 3D Si/ZnO/Ag nanocomb arrays were employed as substrates for
surface-enhanced Raman scattering (SERS). The finite-difference time-domain
simulation result shows that two kinds of inter-Ag-NP nanogaps in the geometry
create a large number of SERS "hot spots," which contributes to the detection
limits for rhodamine-6G as low as 10-12 M and the Raman enhancement factor as
large as 109. The linear dependence between the Raman peak intensities and the
concentrations of thiram provides a new calibration method for rapid and
quantitative detection of trace organic molecules.
PMID- 25121684
TI - Generalized description of spectral incoherent solitons.
AB - Spectral incoherent solitons (SIS) refer to an incoherent solitonic structure
that only can be identified in the frequency domain and which is sustained by
noninstantaneous Raman-like nonlinearities. We provide a generalized formulation
of SIS by considering the generalized nonlinear Schrodinger equation. We show
that nonlinear dispersive effects (e.g., self-steepening) dramatically affect the
structure of SIS, in particular by significantly decelerating their spectral
velocity in frequency space. The wave turbulence description of the problem
reveals an underlying self-organization process: the soliton trajectory in
frequency space is selected in such a way that it allows the system to self
organize into a stationary SIS state.
PMID- 25121686
TI - Modulational instability in dispersion oscillating fiber ring cavities.
AB - We show that the use of a dispersion oscillating fiber in passive cavities
significantly extends the modulational instability to novel high-frequency bands,
which also destabilizes the branches of the steady response that are stable with
homogeneous dispersion. By means of Floquet theory, we obtain the exact explicit
expression for the sideband gain, and a simple analytical estimate for the
frequencies of the maximum gain. Numerical simulations show that stable
stationary trains of pulses can be excited in the cavity.
PMID- 25121685
TI - Abnormal high-Q modes of coupled stadium-shaped microcavities.
AB - It is well known that the strongly deformed microcavity with fully chaotic ray
dynamics cannot support high-Q modes due to its fast chaotic diffusion to the
critical line of refractive emission. Here, we investigate how the Q factor is
modified when two chaotic cavities are coupled, and show that some modes, whose Q
factor is about 10 times higher than that of the corresponding single cavity, can
exist. These abnormal high-Q modes are the result of an optimal combination of
coupling and cavity geometry. As an example, in the coupled stadium-shaped
microcavities, the mode pattern extends over both cavities such that it follows a
whispering-gallery-type mode at both ends, whereas a big coupling spot forms at
the closest contact of the two microcavities. The pattern of such a "rounded bow
tie" mode allows the mode to have a high-Q factor. This mode pattern minimizes
the leakage of light at both ends of the microcavities as the pattern at both
ends is similar to the whispering gallery mode.
PMID- 25121687
TI - Germanium p-i-n avalanche photodetector fabricated by point defect healing
process.
AB - In this Letter, we report Ge p-i-n avalanche photodetectors (APD) with low dark
current (sub 1 MUA below V(R)=5 V), low operating voltage (avalanche breakdown
voltage=8-13 V), and high multiplication gain (440-680) by exploiting a point
defect healing method (between 600 degrees C and 650 degrees C) and optimizing
the doping concentration of the intrinsic region (p-type ~1017 cm-3). In
addition, Raman spectroscopy and electrochemical capacitance voltage analyses
were performed to investigate the junction interfaces in more detail. This
successful demonstration of Ge p-i-n APD with low dark current, low operating
voltage, and high gain is promising for low-power and high-sensitivity Ge PD
applications.
PMID- 25121688
TI - Omnidirectional light absorption of disordered nano-hole structure inspired from
Papilio ulysses.
AB - Butterflies routinely produce nanostructured surfaces with useful properties.
Here, we report a disordered nano-hole structure with ridges inspired by Papilio
ulysses that produce omnidirectional light absorption compared with the common
ordered structure. The result shows that the omnidirectional light absorption is
affected by polarization, the incident angle, and the wavelength. Using the
finite-difference time-domain (FDTD) method, the stable omnidirectional light
absorption is achieved in the structure inspired from the Papilio ulysses over a
wide incident angle range and with various wavelengths. This explains some of the
mysteries of the structure of the Papilio ulysses butterfly. These conclusions
can guide the design of omnidirectional absorption materials.
PMID- 25121689
TI - Distortion-free wide-angle 3D imaging and visualization using off-axially
distributed image sensing.
AB - We propose a new off-axially distributed image sensing (ODIS) using a wide-angle
lens for reconstructing distortion-free wide-angle slice images computationally.
In the proposed system, the wide-angle image sensor captures a wide-angle 3D
scene, and thus the collected information of the 3D objects is severely
distorted. To correct this distortion, we introduce a new correction process
involving a wide-angle lens to the computational reconstruction in ODIS. This
enables us to reconstruct distortion-free, wide-angle slice images for
visualization of 3D objects. Experimental results are carried out to verify the
proposed method. To the best of our knowledge, this is the first time the use of
a wide-angle lens in a multiple-perspective 3D imaging system is described.
PMID- 25121690
TI - Stable localized modes in asymmetric waveguides with gain and loss.
AB - It is shown that asymmetric waveguides with gain and loss can support a stable
propagation of optical beams. This means that the propagation constants of modes
of the corresponding complex optical potential are real. A class of such
waveguides is found from a relation between two spectral problems. A particular
example of an asymmetric waveguide, described by the hyperbolic functions, is
analyzed. The existence and stability of linear modes and of continuous families
of nonlinear modes are demonstrated.
PMID- 25121691
TI - Resolution improvement in laser diode-based pump-probe microscopy with an annular
pupil filter.
AB - We experimentally demonstrate the use of annular beams to improve lateral
resolution in laser-diode-based pump-probe microscopy. We found that the width of
the point-spreading function in the case of the annular pump-probe beams is 162
nm, which is 30% smaller than that of the circular beams (232 nm). Furthermore,
side lobes were efficiently suppressed at the focal plane since the pump-probe
signal is proportional to the product of the two beam intensities. This scheme is
demonstrated for the photothermal signal of nonfluorescent gold nanoparticles and
the stimulated emission signal of fluorescence beads.
PMID- 25121692
TI - Stable planar mesoscopic photonic crystal cavities.
AB - Mesoscopic self-collimation (MSC) in mesoscopic photonic crystals with high
reflectivity is exploited to realize a novel high Q-factor cavity by means of
mesoscopic PhC planar mirrors. These mirrors efficiently confine a mode inside a
planar Fabry-Perot-like cavity, that results from a beam focusing effect that
stabilizes the cavity even for small beam sizes, resembling the focusing behavior
of curved mirrors. Moreover, they show an improved reflectivity with respect to
their standard distributed Bragg reflector counterparts that allows higher
compactness. A Q-factor higher than 104 has been achieved for an optimized 5
period-long mirror cavity. The optimization of the Q-factor and the performances
in terms of energy storage, field enhancement, and confinement are detailed.
PMID- 25121693
TI - Optical injection unlocking for cavity ringdown spectroscopy.
AB - Continuous wave cavity ringdown spectroscopy requires a rapid termination of the
injection of light into the cavity to initiate the decay (i.e., ringdown) event.
We demonstrate a technique that accomplishes this through pulsed optical
injection of a second laser into the main laser, resulting in 20-100 MHz
frequency shifts in the otherwise cavity-locked main laser sufficient to create
ringdown events at 3.5 kHz. Data on the frequency shift as a function of both
main laser current and relative wavelength are presented, as well as a
demonstration that single exponential decays are maintained in the process.
PMID- 25121694
TI - Nonlinear Raman-Nath diffraction of femtosecond laser pulses.
AB - We study the nonlinear Raman-Nath diffraction (NRND) of femtosecond laser pulses
in a 1D periodic nonlinear photonic structure. The calculated second-harmonic
spectra represent frequency combs for different orders of transverse phase
matching. These frequency combs are in close analogy with the well-known spectral
Maker fringes observed in single crystals. The spectral intensity of the second
harmonic experiences a redshift with a propagation angle, which is opposite the
case of Cerenkov nonlinear diffraction. We analyze how NRND is affected by the
group-velocity mismatch between fundamental and second-harmonic pulses and by the
parameters of the structure. Our experimental results prove the theoretical
predictions.
PMID- 25121695
TI - Design of an efficient single photon source from a metallic nanorod dimer: a
quasi-normal mode finite-difference time-domain approach.
AB - We describe how the finite-difference time-domain (FDTD) technique can be used to
compute the quasi-normal mode (QNM) for metallic nano-resonators, which is
important for describing and understanding light-matter interactions in
nanoplasmonics. We use the QNM to model the enhanced spontaneous emission rate
for dipole emitters near a gold nanorod dimer structure using a newly developed
QNM expansion technique. Enhanced single photon emission factors of around 1500
and output beta-factors of around 60% are found near the localized plasmon
resonance.
PMID- 25121696
TI - GHz bandwidth noise eater hybrid optical amplifier: design guidelines.
AB - This Letter describes the design of an optical amplifier system optimized to
reduce the relative intensity noise (RIN) of the input signal, and discloses its
performance in terms of intensity noise reduction and bandwidth, without phase
noise degradation. This polarization-maintaining amplifier is composed of an
erbium-doped fiber amplifier (EDFA) cascaded with a semiconductor optical
amplifier (SOA). The EDFA is sized to feed the SOA with a constant power
corresponding to the optimal saturation level for noise reduction, through
coherent population oscillations. When properly optimized, such an amplifier
provides, simultaneously, 17 dB optical gain, 5.4 dB noise factor, and 20 dB
reduction of the input-RIN across a 3 GHz bandwidth, without any electronics
feedback loop.
PMID- 25121697
TI - Incoherent-light temporal stretching of high-speed intensity waveforms.
AB - We propose and demonstrate experimentally the first incoherent-light scheme for
temporal imaging (magnification) of intensity waveforms. The scheme is based on a
time-domain equivalent of a pinhole camera under incoherent illumination,
involving two dispersive lines and temporal intensity modulation with a short
gate. We report incoherent-light temporal stretching of radiofrequency waveforms
by a magnification factor of 2.86, with a time-bandwidth product exceeding 160,
i.e., a resolution of ~50 ps over a temporal aperture of ~8 ns, totally avoiding
the use of chirp-controlled pulsed lasers. This work opens up new perspectives
for realization of many critical high-speed signal-processing modules using
practical incoherent light-wave schemes.
PMID- 25121698
TI - Diode-pumped microchip Tm:KLu(WO4)2 laser with more than 3 W of output power.
AB - A diode-pumped microchip laser containing a quasi-monolithic plano-plano cavity
is realized on the basis of a Tm:KLu(WO4)2 crystal. The maximum CW output power
is 3.2 W (at an absorbed pump power of 6.8 W) and the slope efficiency as high as
50.4%. The laser is operating at 1946 nm in the TEM00 mode with a M2<1.05.
Microchip operation with Tm:KLu(WO4)2 is, in principle, due to a special crystal
cut along the N(g) optical indicatrix axis. This crystal cut possesses positive
near-spherical thermal lens that provides the required mode stabilization in the
plano-plano cavity. Sensitivity factors of the thermal lens, "generalized" thermo
optic coefficients and constants describing the photoelastic effect are
determined for the monolithic Tm:KLu(WO4)2 crystal.
PMID- 25121699
TI - Method for refractive index measurement of nanoparticles.
AB - A new method of measuring the refractive indices of nanoparticles has been
proposed based on refractive index matching between nanoparticles and surrounding
organic solvents. By finding the most transparent point of the transmittance
spectrum, the refractive index of the nanoparticles is equal to that of the
solvents at the corresponding wavelength. Utilizing a Rayleigh scattering model,
the effects of refractive index mismatching (Deltan) on the transmittance are
investigated under different conditions. Some criteria for getting highly
transparent nanoparticle dispersion and accurate refractive index measurements
are suggested, which can support practical applications for nanomaterials in
optical and optoelectronic applications.
PMID- 25121700
TI - 1 Gbps directed optical decoder based on two cascaded microring resonators.
AB - We report an electro-optic directed optical decoder based on two cascaded
microring resonators (MRRs). PN junctions embedded around the MRRs are employed
to modulate the MRRs through the carrier-injection scheme. The optical decoding
function from a 2-bit electrical signal to a 4-bit optical signal at the speed of
1 Gbps is performed successfully by the device.
PMID- 25121701
TI - Flexible picosecond thulium-doped fiber laser using the active mode-locking
technique.
AB - An all-fiber actively mode-locked thulium-doped fiber laser (AML-TDFL) based on a
10 GHz bandwidth electro-optic intensity modulator (EOM) providing flexible
picosecond pulses at 1980 nm is presented. The EOM is driven by electrical pulses
rather than traditional sine-wave signals. The repetition rate of output pulses
was 21.4 MHz at fundamental mode-locking, which could be scaled up to 1.498 GHz
through the 70th order harmonic mode-locking, and the shortest measured output
pulse width was 38 ps. Furthermore, the output pulse width could be tuned by
either adjusting the modulation frequency with small detuning or changing the
width of these driving electrical pulses without frequency detuning. In our work,
the stability of these mode-locked pulses obtained from the AML-TDFL was
superior; for instance, the measured supermode suppression ratio of 1.498 GHz
pulses train was up to 48 dB.
PMID- 25121702
TI - Holographic patterning of graphene-oxide films by light-driven reduction.
AB - We report on the patterning and reduction of graphene-oxide films by holographic
lithography. Light reduction can be used to engineer low-cost graphene-based
devices by performing a local conversion of insulating oxide into the conductive
graphene. In this work, computer-generated holograms have been exploited to
realize complex graphene patterns in a single shot, different from serial laser
writing or mask-based photolithographic processes. The technique has been further
improved by achieving speckle noise reduction: submicron and diffraction-limited
features have been obtained. In addition we have also demonstrated that the gray
scale lithography capability can be used to obtain different reduction levels in
a single exposure.
PMID- 25121703
TI - Optical microscope for three-dimensional surface displacement and shape
measurements at the microscale.
AB - We report a novel optical microscope for full-field, noncontact measurements of
three-dimensional (3D) surface deformation and topography at the microscale. The
microscope system is based on a seamless integration of the diffraction-assisted
image correlation (DAIC) method with fluorescent microscopy. We experimentally
demonstrate the microscope's capability for 3D measurements with submicrometer
spatial resolution and subpixel measurement accuracy.
PMID- 25121704
TI - A Raman waveplate for spinor Bose-Einstein condensates.
AB - We demonstrate a waveplate for a pseudo-spin-1/2 Bose-Einstein condensate (BEC)
using a two-photon Raman interaction. The angle of the waveplate is set by the
relative phase of the optical fields, and the retardance is controlled by the
pulse area. The waveplate allows us to image maps of the Stokes parameters of a
BEC and thereby measure its relative ground-state phase. We demonstrate the
waveplate by measuring the Stokes parameters of a coreless vortex.
PMID- 25121705
TI - Heterodyne-detected and ultrafast time-resolved second-harmonic generation for
sensitive measurements of charge transfer.
AB - In organic photovoltaics many key ultrafast processes occur at the interface
between electron donor and acceptor molecules. Traditional ultrafast
spectroscopies, such as pump-probe or time-resolved fluorescence, are not ideal
for studying the interface because most of their signal is from the bulk
material. Time-resolved second-harmonic generation (TRSHG) spectroscopy solves
this problem by only generating signal from the interface. We demonstrate an
optically heterodyned TRSHG to reduce the impact of stray light, enhance
sensitivity, and detect the full complex signal field.
PMID- 25121706
TI - In situ detection of laser-induced slip initiation on the silicon wafer surface.
AB - We propose a real-time in situ method to detect slip initiation on the surface of
silicon wafers during high-power laser beam irradiation. In this method, light is
collected from the surface of a silicon wafer subjected to laser irradiation.
When the slip is initiated, it strongly scatters the laser beam, allowing
detection of the time of the slip initiation based on the resulting sudden
increase in the scattering signal. To demonstrate the performance of this method,
a silicon wafer specimen was illuminated by a near-infrared continuous-wave fiber
laser beam (of wavelength 1070 nm) at four different laser powers, and the
scattered light was detected. The scattering signal increased suddenly at the
time of slip initiation. To confirm the occurrence of slip, the surface
morphologies of the silicon specimens after laser irradiation were analyzed using
an optical microscope; surface slips were observed only in the specimens for
which the sudden increase in scattering had been detected. Thus, the proposed
method is shown to be very effective for the real-time in situ detection of
surface slip initiation induced by high-power laser beam irradiation on silicon
wafers.
PMID- 25121707
TI - Experimental study on the dynamics of polarized strong optical injection in 1550
nm VCSELs.
AB - We have experimentally analyzed the dynamics of polarized strong optical
injection in 1550 nm vertical-cavity surface-emitting lasers (VCSELs). The
locking ranges of optical injection-locked (OIL) VCSELs are experimentally
measured in different states of polarized strong optical injection. Based on our
novel ellipse model, the influence of the polarization state of strong injection
light is quantitatively studied for the first time.
PMID- 25121708
TI - Radiologic Manifestations of Senile Lymph Nodes in the Popliteal Fossa.
AB - PURPOSE: To determine the radiologic manifestations of senile lymph nodes in the
popliteal fossa for radiologic and clinical application. METHODS: A total of six
lower extremities from four unembalmed human cadavers were studied. Under a
surgical microscope, 6% hydrogen peroxide was used to detect the lymphatic
vessels commencing from the foot and leg. A 30-gauge needle was inserted into the
vessels and injected with a radio-opaque lead oxide mixture. The specimens were
radiographed and photographed to demonstrate the lymph nodes in the popliteal
fossa. The final results were transferred to the computer for image analysis.
RESULTS: An average of two lymph nodes (range 1 to 3) were found in the popliteal
fossa of the lower extremity. They were divided into superficial and deep
popliteal groups. The superficial group was located in the superficial layer of
the popliteal fossa around the small saphenous vein (SSV). The deep group was
close to the popliteal surface of the femur and always located next to the
popliteal vein. All lymph nodes were transparent in appearance and contained
coiled lymphatic tubules. The size and density of the tubules varied. CONCLUSION:
The radiologic manifestations of senile lymph nodes in the popliteal fossa have
been presented and discussed to upgrade our radiologic and anatomical knowledge.
This will be of benefit for radiologic and clinical applications.
PMID- 25121709
TI - Enhancing Gibbs sampling method for motif finding in DNA with initial graph
representation of sequences.
AB - Finding short patterns with residue variation in a set of sequences is still an
open problem in genetics, since motif-finding techniques on DNA and protein
sequences are inconclusive on real data sets and their performance varies on
different species. Hence, finding new algorithms and evolving established methods
are vital to further understanding of genome properties and the mechanisms of
protein development. In this work, we present an approach to finding functional
motifs in DNA sequences in connection to Gibbs sampling method. Starting points
in the search space are partly determined via graphical representation of input
sequences opposed to completely random initial points with the standard Gibbs
sampling. Our algorithm is evaluated on synthetic as well as on real data sets by
using several statistics, such as sensitivity, positive predictive value,
specificity, performance, and correlation coefficient. Additionally, a comparison
between our algorithm and the basic standard Gibbs sampling algorithm is made to
show improvement in accuracy, repeatability, and performance.
PMID- 25121710
TI - Health department use of social media to identify foodborne illness - Chicago,
Illinois, 2013-2014.
AB - An estimated 55 million to 105 million persons in the United States experience
acute gastroenteritis caused by foodborne illness each year, resulting in costs
of $2-$4 billion annually. Many persons do not seek treatment, resulting in
underreporting of the actual number of cases and cost of the illnesses. To
prevent foodborne illness, local health departments nationwide license and
inspect restaurants and track and respond to foodborne illness complaints. New
technology might allow health departments to engage with the public to improve
foodborne illness surveillance. For example, the New York City Department of
Health and Mental Hygiene examined restaurant reviews from an online review
website to identify foodborne illness complaints. On March 23, 2013, the Chicago
Department of Public Health (CDPH) and its civic partners launched FoodBorne
Chicago, a website (https://www.foodbornechicago.org) aimed at improving food
safety in Chicago by identifying and responding to complaints on Twitter about
possible foodborne illnesses. In 10 months, project staff members responded to
270 Twitter messages (tweets) and provided links to the FoodBorne Chicago
complaint form. A total of 193 complaints of possible foodborne illness were
submitted through FoodBorne Chicago, and 133 restaurants in the city were
inspected. Inspection reports indicated 21 (15.8%) restaurants failed inspection,
and 33 (24.8%) passed with conditions indicating critical or serious violations.
Eight tweets and 19 complaint forms to FoodBorne Chicago described seeking
medical treatment. Collaboration between public health professionals and the
public via social media might improve foodborne illness surveillance and
response. CDPH is working to disseminate FoodBorne Chicago via freely available
open source software.
PMID- 25121711
TI - Sugar-sweetened beverage consumption among adults -- 18 states, 2012.
AB - Reducing consumption of calories from added sugars is a recommendation of the
2010 Dietary Guidelines for Americans and an objective of Healthy People 2020.
Sugar-sweetened beverages (SSB) are major sources of added sugars in the diets of
U.S. residents. Daily SSB consumption is associated with obesity and other
chronic health conditions, including diabetes and cardiovascular disease. U.S.
adults consumed an estimated average of 151 kcal/day of SSB during 2009-2010,
with regular (i.e., nondiet) soda and fruit drinks representing the leading
sources of SSB energy intake. However, there is limited information on state
specific prevalence of SSB consumption. To assess regular soda and fruit drink
consumption among adults in 18 states, CDC analyzed data from the 2012 Behavioral
Risk Factor Surveillance System (BRFSS). Among the 18 states surveyed, 26.3% of
adults consumed regular soda or fruit drinks or both >=1 times daily. By state,
the prevalence ranged from 20.4% to 41.4%. Overall, consumption of regular soda
or fruit drinks was most common among persons aged 18-34 years (24.5% for regular
soda and 16.6% for fruit drinks), men (21.0% and 12.3%), non-Hispanic blacks
(20.9% and 21.9%), and Hispanics (22.6% and 18.5%). Persons who want to reduce
added sugars in their diets can decrease their consumption of foods high in added
sugars such as candy, certain dairy and grain desserts, sweetened cereals,
regular soda, fruit drinks, sweetened tea and coffee drinks, and other SSBs.
States and health departments can collaborate with worksites and other community
venues to increase access to water and other healthful beverages.
PMID- 25121712
TI - Prevention and control of seasonal influenza with vaccines: recommendations of
the Advisory Committee on Immunization Practices (ACIP) -- United States, 2014-15
influenza season.
AB - This report updates the 2013 recommendations by the Advisory Committee on
Immunization Practices (ACIP) regarding use of seasonal influenza vaccines.
Updated information for the 2014-15 influenza season includes 1) antigenic
composition of U.S. seasonal influenza vaccines; 2) vaccine dose considerations
for children aged 6 months through 8 years; and 3) a preference for the use, when
immediately available, of live attenuated influenza vaccine (LAIV) for healthy
children aged 2 through 8 years, to be implemented as feasible for the 2014-15
season but not later than the 2015-16 season. Information regarding issues
related to influenza vaccination not addressed in this report is available in the
2013 ACIP seasonal influenza recommendations.
PMID- 25121713
TI - Notes from the field: hospitalizations for respiratory disease among
unaccompanied children from Central America - multiple States, June-July 2014.
AB - During October 2013-June 2014, approximately 54,000 unaccompanied children,
mostly from the Central American countries of El Salvador, Guatemala, and
Honduras, were identified attempting entry into the United States from Mexico,
exceeding numbers reported in previous years. Once identified in the United
States, U.S. Customs and Border Protection, an agency of the U.S. Department of
Homeland Security, processes the unaccompanied children and transfers them to the
Office of Refugee Resettlement (ORR), an office of the Administration for
Children and Families, U.S. Department of Health and Human Services. ORR cares
for the children in shelters until they can be released to a sponsor, typically a
parent or relative, who can care for the child while their immigration case is
processed. In June 2014, in response to the increased number of unaccompanied
children, U.S. Customs and Border Protection expanded operations to accommodate
children at a processing center in Nogales, Arizona. ORR, together with the U.S.
Department of Defense, opened additional large temporary shelters for the
children at Lackland Air Force Base, Texas; U.S. Army Garrison Ft. Sill,
Oklahoma; and Naval Base Ventura County, California.
PMID- 25121714
TI - Notes from the field: malnutrition and elevated mortality among refugees from
South Sudan - Ethiopia, June-July 2014.
AB - As a result of armed civil conflict in South Sudan that started in mid-December
of 2013, an estimated 1.1 million persons were internally displaced, and
approximately 400,000 refugees fled South Sudan to neighboring countries
(primarily to Ethiopia, Uganda, Sudan, and Kenya). Refugees from South Sudan
arriving in Ethiopia are sheltered in three refugee camps located in Gambella
region: Leitchuor, Kule, and Tierkidi. The camps were established during January
May 2014 and have estimated refugee populations of 47,000, 51,000, and 50,000,
respectively. Reports from health clinics and humanitarian agencies providing
assistance to refugees suggested poor nutritional status of arriving refugees and
elevated mortality rates. To assess the nutritional status of refugee children
aged 6-59 months and mortality rates (crude [all ages] and aged <5 years), the
Administration for Refugee and Returnee Affairs (an Ethiopian government aid
agency), the United Nations High Commissioner for Refugees, World Food Programme,
and United Nations Children's Fund, in collaboration with CDC, conducted cross
sectional population-representative surveys in Leitchuor, Kule, and Tierkidi
camps during June-July 2014. Anthropometric measurements in children were taken
using standard procedures, and nutritional status was classified based on 2006
World Health Organization (WHO) growth standards. Hemoglobin was measured using
HemoCue Hb 301. Anemia was diagnosed according to WHO thresholds. Retrospective
mortality rates in Leitchuor and Kule were measured using a household census
method.
PMID- 25121715
TI - Alginate gelation-induced cell death during laser-assisted cell printing.
AB - Modified laser-induced forward transfer has emerged as a promising bioprinting
technique. Depending on the operating conditions and cell properties, laser cell
printing may cause cell injury and even death, which should be carefully
elucidated for it to be a viable technology. This study has investigated the
effects of alginate gelation, gelation time, alginate concentration, and laser
fluence on the post-transfer cell viability of NIH 3T3 fibroblasts. Sodium
alginate and calcium chloride are used as the gel precursor and gel reactant
solution to form cell-laden alginate microspheres. It is found that the effects
of gelation depend on the duration of gelation. Two-minute gelation is observed
to increase the cell viability after 24 h incubation, mainly due to the
protective cushion effect of the forming gel membrane during droplet landing.
Despite the cushion effect from 10 min gelation, it is observed that the cell
viability decreases after 24 h incubation because of the forming thick gel
membrane that reduces nutrient and oxygen diffusion from the culture medium. In
addition, the cell viability after 24 h incubation decreases as the laser fluence
or alginate concentration increases.
PMID- 25121716
TI - Binding of a monoclonal antibody to the phospholamban cytoplasmic domain
interferes with the channel activity of phospholamban reconstituted in a tethered
bilayer lipid membrane.
AB - Phospholamban (PLN), a membrane protein present in the sarcoplasmic reticulum of
cardiac myocytes, is a crucial regulator of cardiac function. It is known that
PLN appears as a monomer and as a pentamer. However, the role of the PLN pentamer
and its ability to generate an ion channel are a matter of debate. To address
this issue we employed an experimental approach that combines electrochemical
impedance spectroscopy and surface plasmon resonance measurements. In particular,
we investigated the channel activity of wild-type PLN reconstituted in a tethered
bilayer lipid membrane (tBLM) on a gold surface. Our results indicate that
reconstituted PLN can generate ion-conducting channels in a tBLM. Experiments
with a PLN monoclonal antibody support an oriented incorporation of PLN in the
tBLM. We show that the binding of the antibody to the PLN cytoplasmic domain
interferes with PLN channel activity.
PMID- 25121717
TI - A DFT study on the reaction mechanism of dimerization of methyl methacrylate
catalyzed by N-heterocyclic carbene.
AB - Reaction mechanisms of the N-heterocyclic carbene (NHC)-catalyzed dimerization of
methyl methacrylate were studied using density functional theory (DFT) at the M05
2X/6-31G(d,p) level of theory. Four possible reaction channels (A, B, C, and D)
have been investigated in this work. Particularly, we proposed a novel reaction
pathway, where the proton transfers are assisted by a different molecule. The
calculated results indicate that the channels B and D are more energetically
favourable channels. The obtained results suggest that the E-isomer product is
the main product, which is in agreement with the experimental results. Further
calculations and analyses of global and local reactivity indices reveal the role
of the NHC catalysts in the title reaction. The mechanistic insights gained are
valuable for not only rational design of more efficient NHC catalysts but also
for understanding the similar reaction mechanism.
PMID- 25121718
TI - Trimethyltin-mediated covalent gold-carbon bond formation.
AB - We study the formation of covalent gold-carbon bonds in benzyltrimethylstannane
(C10H16Sn) deposited on Au in ultra-high-vacuum conditions. Through X-ray
photoemission spectroscopy and X-ray absorption measurements, we find that the
molecule fragments at the Sn-benzyl bond when exposed to Au surfaces at
temperatures as low as -110 degrees C. The resulting benzyl species is
stabilized by the presence of Au(111) but only forms covalent Au-C bonds on more
reactive Au surfaces like Au(110). We also present spectroscopic proof for the
existence of an electronic "gateway" state localized on the Au-C bond that is
responsible for its unique electronic properties. Finally, we use DFT-based
nudged elastic band calculations to elucidate the crucial role played by the
under-coordinated Au surface in the formation of Au-C bonds.
PMID- 25121721
TI - Rapid spectrophotometric method for determining surface free energy of microalgal
cells.
AB - Microalgae are one of the most promising renewable energy sources with
environmental sustainability. The surface free energy of microalgal cells
determines their biofouling and bioflocculation behavior and hence plays an
important role in microalgae cultivation and harvesting. To date, the surface
energetic properties of microalgal cells are still rarely studied. We developed a
novel spectrophotometric method for directly determining the surface free energy
of microalgal cells. The principles of this method are based on analyzing
colloidal stability of microalgae suspensions. We have shown that this method can
effectively differentiate the surface free energy of four microalgal strains,
i.e., marine Chlorella sp., marine Nannochloris oculata, freshwater autotrophic
Chlorella sp., and freshwater heterotrophic Chlorella sp. With advantages of high
throughput and simplicity, this new spectrophotometric method has the potential
to evolve into a standard method for measuring the surface free energy of cells
and abiotic particles.
PMID- 25121719
TI - Leukocyte activity in patients with ST-segment elevation acute myocardial
infarction treated with anakinra.
AB - Anakinra, the recombinant form of the human interleukin (IL)-1 receptor
antagonist, blunts the acute systemic inflammatory response in patients with ST
segment elevation myocardial infarction (STEMI), by determining a fall in
peripheral blood leukocyte and plasma C-reactive protein levels. The aim of the
present study was to determine the effects of anakinra on the activity of
leukocytes measured ex vivo. Blood was collected 72 h after admission in 17
patients enrolled in the Virginia Commonwealth University-Anakirna Remodeling
Trial (2) (VCU-ART2) and randomly treated with anakinra (N=7) or placebo (N=10).
Whole blood was cultured at 37 degrees C for 24 h to measure spontaneous
production of IL-6 or stimulated with Escherichia coli lipopolysaccharide (LPS)
for toll-like receptor (TLR)-4 or heat-killed Staphylococcus epidermidis (SE) for
TLR-2 activation. The cultures of anakinra-treated patients produced
significantly less IL-6 spontaneously (71 pg/mL [27-114]) compared with placebo
treated patients (290 pg/mL [211-617], p=0.005). LPS- or SE-induced IL-6
production, on the other hand, was not statistically different between anakinra
versus placebo-treated patients (344 pg/mL [94-560] versus 370 pg/mL [306-991],
p=0.32 for LPS, and 484 pg/mL [77-612] versus 615 pg/mL [413-871], p=0.31 for SE,
respectively). IL-1 blockade with anakinra in STEMI patients results in reduced
spontaneous leukocyte activity ex vivo without impairing the responsiveness to
bacterial stimuli.
PMID- 25121720
TI - The identification of perillyl alcohol glycosides with improved antiproliferative
activity.
AB - A facile route to perillyl alcohol (POH) differential glycosylation and the
corresponding synthesis of a set of 34 POH glycosides is reported. Subsequent in
vitro studies revealed a sugar dependent antiproliferative activity and the
inhibition of S6 ribosomal protein phosphorylation as a putative mechanism of
representative POH glycosides. The most active glycoside from this cumulative
study (4'-azido-d-glucoside, PG9) represents one of the most cytotoxic POH
analogues reported to date.
PMID- 25121722
TI - Low-cost motility tracking system (LOCOMOTIS) for time-lapse microscopy
applications and cell visualisation.
AB - Direct visualisation of cells for the purpose of studying their motility has
typically required expensive microscopy equipment. However, recent advances in
digital sensors mean that it is now possible to image cells for a fraction of the
price of a standard microscope. Along with low-cost imaging there has also been a
large increase in the availability of high quality, open-source analysis
programs. In this study we describe the development and performance of an
expandable cell motility system employing inexpensive, commercially available
digital USB microscopes to image various cell types using time-lapse and perform
tracking assays in proof-of-concept experiments. With this system we were able to
measure and record three separate assays simultaneously on one personal computer
using identical microscopes, and obtained tracking results comparable in quality
to those from other studies that used standard, more expensive, equipment. The
microscopes used in our system were capable of a maximum magnification of 413.6*.
Although resolution was lower than that of a standard inverted microscope we
found this difference to be indistinguishable at the magnification chosen for
cell tracking experiments (206.8*). In preliminary cell culture experiments using
our system, velocities (mean um/min +/- SE) of 0.81 +/- 0.01 (Biomphalaria
glabrata hemocytes on uncoated plates), 1.17 +/- 0.004 (MDA-MB-231 breast cancer
cells), 1.24 +/- 0.006 (SC5 mouse Sertoli cells) and 2.21 +/- 0.01 (B. glabrata
hemocytes on Poly-L-Lysine coated plates), were measured and are consistent with
previous reports. We believe that this system, coupled with open-source analysis
software, demonstrates that higher throughput time-lapse imaging of cells for the
purpose of studying motility can be an affordable option for all researchers.
PMID- 25121724
TI - Endobronchial ultrasound elastography in the diagnosis of mediastinal and hilar
lymph nodes.
AB - OBJECTIVE: Endobronchial ultrasound elastography is a new technique for
describing the stiffness of tissue during endobronchial ultrasound-guided
transbronchial needle aspiration. The aims of this study were to evaluate the
utility of endobronchial ultrasound elastography for mediastinal and hilar lymph
nodes, and to compare the elastographic patterns of lymph nodes with results from
endobronchial ultrasound-guided transbronchial needle aspiration. METHODS:
Seventy-five lymph nodes were evaluated. A convex probe endobronchial ultrasound
was used with a new endoscopic ultrasound processor to assess elastographic
patterns that were classified based on color distribution as follows: Type 1,
predominantly non-blue (green, yellow and red); Type 2, part blue, part non-blue
(green, yellow and red); Type 3, predominantly blue. The elastographic patterns
were compared with the final pathologic results from endobronchial ultrasound
guided transbronchial needle aspiration. RESULTS: On pathological evaluation of
the lymph nodes, 33 were benign and 42 were malignant. The lymph nodes that were
classified as Type 1 on endobronchial ultrasound elastography were benign in
24/24 (100%); for Type 2 lymph nodes, 6/14 (46.9%) were benign and 8/14 (57.1%)
were malignant; Type 3 lymph nodes were benign in 2/37 (5.4%) and malignant in
35/37 (94.6%). In classifying Type 1 as 'benign' and Type 3 as 'malignant,' the
sensitivity, specificity, positive predictive value, negative predictive value
and diagnostic accuracy rates were 100, 92.3, 94.6, 100 and 96.7%, respectively.
CONCLUSIONS: Endobronchial ultrasound elastography of mediastinal and hilar lymph
nodes is a noninvasive technique that can be performed reliably and may be
helpful in the prediction of nodal metastasis during endobronchial ultrasound
guided transbronchial needle aspiration.
PMID- 25121725
TI - On resilience and acceptance in the transition to palliative care at the end of
life.
AB - Specialist palliative care is a prominent and expanding site of health service
delivery, providing highly specialised care to people at the end of life. Its
focus on the delivery of specialised life-enhancing care stands in contrast to
biomedicine's general tendency towards life-prolonging intervention. This
philosophical departure from curative or life-prolonging care means that
transitioning patients can be problematic, with recent work suggesting a wide
range of potential emotional, communication and relational difficulties for
patients, families and health professionals. Yet, we know little about terminally
ill patients' lived experiences of this complex transition. Here, through
interviews with 40 inpatients in the last few weeks of life, we explore their
embodied and relational experiences of the transition to inpatient care,
including their accounts of an ethic of resilience in pre-palliative care and an
ethic of acceptance as they move towards specialist palliative care. Exploring
the relationship between resilience and acceptance reveals the opportunities, as
well as the limitations, embedded in the normative constructs that inflect
individual experience of this transition. This highlights a contradictory dynamic
whereby participants' experiences were characterised by talk of initiating
change, while also acquiescing to the terminal progression of their illness.
PMID- 25121726
TI - Dynamic alignment of transtibial prostheses through visualization of socket
reaction moments.
AB - BACKGROUND AND AIM: Dynamic alignment of transtibial prostheses is generally
performed based on visual interpretation of gait without the benefit of any
kinetic analysis in the clinic. The aim of this technical note was to present and
discuss the possibilities of assisting dynamic alignment of transtibial
prostheses through visualization of socket reaction moments. TECHNIQUE: Smart
PyramidTM (currently EuropaTM) was used to measure the socket reaction moments
under various alignment conditions from an amputee with transtibial prosthesis.
The socket reaction moments were plotted to visualize the effect of alignment
changes on them, and they were clinically interpreted. DISCUSSION: Socket
reaction moments could complement information available to prosthetists to
optimize prosthetic alignment. They could be used to reduce excessive loading on
sensitive areas, to improve gait stability, or to communicate the outcome of
dynamic alignment with the amputees. Further research is needed to identify the
contribution of kinematics and kinetics for optimal alignment. CLINICAL
RELEVANCE: Dynamic alignment of transtibial prostheses is currently tuned
subjectively based on prosthetists' experiences and skills. Socket reaction
moments may potentially provide objective information for prosthetists to align
transtibial prostheses in the clinic.
PMID- 25121727
TI - Collaboration between medical and veterinary professions on the problem of dog
bites.
PMID- 25121728
TI - Hematology as a diagnostic tool in bovine medicine.
AB - The objective of the current review is to provide the reader with an overview of
the bovine hematological profile. Sample collection, bovine reference ranges, and
cattle-specific characteristics of erythrocyte, leukocyte, and platelet
parameters are reviewed. Furthermore, diseases associated with abnormalities in
the complete blood cell count of cattle are discussed.
PMID- 25121730
TI - Systematic comparison of non-invasive measures for the assessment of atrial
fibrillation complexity: a step forward towards standardization of atrial
fibrillation electrogram analysis.
AB - AIMS: To present a comparison of electrocardiogram-based non-invasive measures of
atrial fibrillation (AF) substrate complexity computed on invasive animal
recordings to discriminate between short-term and long-term AF. The final
objective is the selection of an optimal sub-set of measures for AF complexity
assessment. METHODS AND RESULTS: High-density epicardial direct contact mapping
recordings (234 leads) were acquired from the right and the left atria of 17
goats in which AF was induced for 3 weeks (short-term AF group, N = 10) and 6
months (long-term AF group, N = 7). Several non-invasive measures of AF
organization proposed in the literature in the last decade were investigated to
assess their power in discriminating between the short-term and long-term group.
The best performing measures were identified, which when combined attained a
correct classification rate of 100%. Their ability to predict standard invasive
AF complexity measures was also tested, showing an average R(2) of 0.73 +/- 0.04.
CONCLUSION: An optimal set of measures of the AF substrate complexity was
identified out of the set of non-invasive measures analysed in this study. These
measures may contribute to improve patient-tailored diagnosis and therapy of
sustained AF.
PMID- 25121729
TI - PDGF-BB does not accelerate healing in diabetic mice with splinted skin wounds.
AB - Topical application of platelet-derived growth factor-BB (PDGF-BB) is considered
to accelerate tissue repair of impaired chronic wounds. However, the vast
literature is plagued with conflicting reports of its efficacy in animal models
and this is often influenced by a wide array of experimental variables making it
difficult to compare the results across the studies. To mitigate the confounding
variables that influence the efficacy of topically applied PDGF-BB, we used a
controlled full thickness splinted excisional wound model in db/db mice (type 2
diabetic mouse model) for our investigations. A carefully-defined silicone
splinted wound model, with reduced wound contraction, controlled splint and
bandage maintenance, allowing for healing primarily by reepithelialization was
employed. Two splinted 8 mm dorsal full thickness wounds were made in db/db mice.
Wounds were topically treated once daily with either 3 ug PDGF-BB in 30 ul of 5%
PEG-PBS vehicle or an equal volume of vehicle for 10 days. Body weights, wound
contraction, wound closure, reepithelialization, collagen content, and wound bed
inflammation were evaluated clinically and histopathologically. The bioactivity
of PDGF-BB was confirmed by in vitro proliferation assay. PDGF-BB, although
bioactive in vitro, failed to accelerate wound healing in vivo in the db/db mice
using the splinted wound model. Considering that the predominant mechanism of
wound healing in humans is by re-epithelialization, the most appropriate model
for evaluating therapeutics is one that uses splints to prevent excessive wound
contraction. Here, we report that PDGF-BB does not promote wound closure by re
epithelialization in a murine splinted wound model. Our results highlight that
the effects of cytoactive factors reported in vivo ought to be carefully
interpreted with critical consideration of the wound model used.
PMID- 25121732
TI - Six in 10 doctors in Scotland plan to vote against independence.
PMID- 25121734
TI - One-dimensional titanium dioxide nanomaterials: nanotubes.
PMID- 25121731
TI - Nitric oxide from IFNgamma-primed macrophages modulates the antimicrobial
activity of beta-lactams against the intracellular pathogens Burkholderia
pseudomallei and Nontyphoidal Salmonella.
AB - Our investigations show that nonlethal concentrations of nitric oxide (NO)
abrogate the antibiotic activity of beta-lactam antibiotics against Burkholderia
pseudomallei, Escherichia coli and nontyphoidal Salmonella enterica serovar
Typhimurium. NO protects B. pseudomallei already exposed to beta-lactams,
suggesting that this diatomic radical tolerizes bacteria against the
antimicrobial activity of this important class of antibiotics. The concentrations
of NO that elicit antibiotic tolerance repress consumption of oxygen (O2), while
stimulating hydrogen peroxide (H2O2) synthesis. Transposon insertions in genes
encoding cytochrome c oxidase-related functions and molybdenum assimilation
confer B. pseudomallei a selective advantage against the antimicrobial activity
of the beta-lactam antibiotic imipenem. Cumulatively, these data support a model
by which NO induces antibiotic tolerance through the inhibition of the electron
transport chain, rather than by potentiating antioxidant defenses as previously
proposed. Accordingly, pharmacological inhibition of terminal oxidases and
nitrate reductases tolerizes aerobic and anaerobic bacteria to beta-lactams. The
degree of NO-induced beta-lactam antibiotic tolerance seems to be inversely
proportional to the proton motive force (PMF), and thus the dissipation of
DeltaH+ and DeltaPsi electrochemical gradients of the PMF prevents beta-lactam
mediated killing. According to this model, NO generated by IFNgamma-primed
macrophages protects intracellular Salmonella against imipenem. On the other
hand, sublethal concentrations of imipenem potentiate the killing of B.
pseudomallei by NO generated enzymatically from IFNgamma-primed macrophages. Our
investigations indicate that NO modulates the antimicrobial activity of beta
lactam antibiotics.
PMID- 25121735
TI - Subverting ER-stress towards apoptosis by nelfinavir and curcumin coexposure
augments docetaxel efficacy in castration resistant prostate cancer cells.
AB - Despite its side-effects, docetaxel (DTX) remains a first-line treatment against
castration resistant prostate cancer (CRPC). Therefore, strategies to increase
its anti-tumor efficacy and decrease its side effects are critically needed.
Targeting of the constitutive endoplasmic reticulum (ER) stress in cancer cells
is being investigated as a chemosensitization approach. We hypothesized that the
simultaneous induction of ER-stress and suppression of PI3K/AKT survival pathway
will be a more effective approach. In a CRPC cell line, C4-2B, we observed
significant (p<0.005) enhancement of DTX-induced cytotoxicity following
coexposure to thapsigargin and an AKT-inhibitor. However, since these two agents
are not clinically approved, we investigated whether a combination of nelfinavir
(NFR) and curcumin (CUR), known to target both these metabolic pathways, can
similarly increase DTX cytotoxicity in CRPC cells. Within 24 hrs post-exposure to
physiologic concentrations of NFR (5 uM) and CUR (5 uM) a significantly (p<0.005)
enhanced cytotoxicity was evident with low concentration of DTX (10 nM). This 3
drug combination rapidly increased apoptosis in aggressive C4-2B cells, but not
in RWPE-1 cells or in primary prostate epithelial cells (PrEC). Comparative
molecular studies revealed that this 3-drug combination caused a more pronounced
suppression of phosphorylated-AKT and higher induction in phosphorylated
eIF2alpha in C4-2B cells, as compared to RWPE-1 cells. Acute exposure (3-9 hrs)
to this 3-drug combination intensified ER-stress induced pro-apoptotic markers,
i.e. ATF4, CHOP, and TRIB3. At much lower concentrations, chronic (3 wks)
exposures to these three agents drastically reduced colony forming units (CFU) by
C4-2B cells. In vivo studies using mice containing C4-2B tumor xenografts showed
significant (p<0.05) enhancement of DTX's (10 mg/kg) anti-tumor efficacy
following coexposure to NFR (20 mg/kg) & CUR (100 mg/kg). Immunohistochemical
(IHC) analyses of tumor sections indicated decreased Ki-67 staining and increased
TUNEL intensity in mice exposed to the 3-drug combination. Therefore, subverting
ER-stress towards apoptosis using adjuvant therapy with NFR and CUR can
chemosensitize the CRPC cells to DTX therapy.
PMID- 25121733
TI - Gene expansion shapes genome architecture in the human pathogen Lichtheimia
corymbifera: an evolutionary genomics analysis in the ancient terrestrial
mucorales (Mucoromycotina).
AB - Lichtheimia species are the second most important cause of mucormycosis in
Europe. To provide broader insights into the molecular basis of the pathogenicity
associated traits of the basal Mucorales, we report the full genome sequence of
L. corymbifera and compared it to the genome of Rhizopus oryzae, the most common
cause of mucormycosis worldwide. The genome assembly encompasses 33.6 MB and
12,379 protein-coding genes. This study reveals four major differences of the L.
corymbifera genome to R. oryzae: (i) the presence of an highly elevated number of
gene duplications which are unlike R. oryzae not due to whole genome duplication
(WGD), (ii) despite the relatively high incidence of introns, alternative
splicing (AS) is not frequently observed for the generation of paralogs and in
response to stress, (iii) the content of repetitive elements is strikingly low
(<5%), (iv) L. corymbifera is typically haploid. Novel virulence factors were
identified which may be involved in the regulation of the adaptation to iron
limitation, e.g. LCor01340.1 encoding a putative siderophore transporter and
LCor00410.1 involved in the siderophore metabolism. Genes encoding the
transcription factors LCor08192.1 and LCor01236.1, which are similar to GATA type
regulators and to calcineurin regulated CRZ1, respectively, indicating an
involvement of the calcineurin pathway in the adaption to iron limitation. Genes
encoding MADS-box transcription factors are elevated up to 11 copies compared to
the 1-4 copies usually found in other fungi. More findings are: (i) lower content
of tRNAs, but unique codons in L. corymbifera, (ii) Over 25% of the proteins are
apparently specific for L. corymbifera. (iii) L. corymbifera contains only 2/3 of
the proteases (known to be essential virulence factors) in comparison to R.
oryzae. On the other hand, the number of secreted proteases, however, is roughly
twice as high as in R. oryzae.
PMID- 25121737
TI - A role for H2S in the microcirculation of newborns: the major metabolite of H2S
(thiosulphate) is increased in preterm infants.
AB - Excessive vasodilatation during the perinatal period is associated with
cardiorespiratory instability in preterm neonates. Little evidence of the
mechanisms controlling microvascular tone during circulatory transition exists.
We hypothesised that hydrogen sulphide (H2S), an important regulator of
microvascular reactivity and central cardiac function in adults and animal
models, may contribute to the vasodilatation observed in preterm newborns. Term
and preterm neonates (24-43 weeks gestational age) were studied. Peripheral
microvascular blood flow was assessed by laser Doppler. Thiosulphate, a urinary
metabolite of H2S, was determined by high performance liquid chromatography as a
measure of 24 hr total body H2S turnover for the first 3 days of postnatal life.
H2S turnover was greatest in very preterm infants and decreased with increasing
gestational age (p = 0.0001). H2S turnover was stable across the first 72 hrs of
life in older neonates. In very preterm neonates, H2S turnover increased
significantly from day 1 to 3 (p =0.0001); and males had higher H2S turnover than
females (p = 0.04). A significant relationship between microvascular blood flow
and H2S turnover was observed on day 2 of postnatal life (p = 0.0004). H2S may
play a role in maintaining microvascular tone in the perinatal period. Neonates
at the greatest risk of microvascular dysfunction characterised by inappropriate
peripheral vasodilatation--very preterm male neonates--are also the neonates with
highest levels of total body H2S turnover suggesting that overproduction of this
gasotransmitter may contribute to microvascular dysfunction in preterms.
Potentially, H2S is a target to selectively control microvascular tone in the
circulation of newborns.
PMID- 25121736
TI - Diverse host-seeking behaviors of skin-penetrating nematodes.
AB - Skin-penetrating parasitic nematodes infect approximately one billion people
worldwide and are responsible for some of the most common neglected tropical
diseases. The infective larvae of skin-penetrating nematodes are thought to
search for hosts using sensory cues, yet their host-seeking behavior is poorly
understood. We conducted an in-depth analysis of host seeking in the skin
penetrating human parasite Strongyloides stercoralis, and compared its behavior
to that of other parasitic nematodes. We found that Str. stercoralis is highly
mobile relative to other parasitic nematodes and uses a cruising strategy for
finding hosts. Str. stercoralis shows robust attraction to a diverse array of
human skin and sweat odorants, most of which are known mosquito attractants.
Olfactory preferences of Str. stercoralis vary across life stages, suggesting a
mechanism by which host seeking is limited to infective larvae. A comparison of
odor-driven behavior in Str. stercoralis and six other nematode species revealed
that parasite olfactory preferences reflect host specificity rather than
phylogeny, suggesting an important role for olfaction in host selection. Our
results may enable the development of new strategies for combating harmful
nematode infections.
PMID- 25121738
TI - Combinatorial G-CSF/AMD3100 treatment in cardiac repair after myocardial
infarction.
AB - AIMS: Several studies suggest that circulating bone marrow derived stem cells
promote the regeneration of ischemic tissues. For hematopoietic stem cell
transplantation combinatorial granulocyte-colony stimulating factor (G
CSF)/Plerixafor (AMD3100) administration was shown to enhance mobilization of
bone marrow derived stem cells compared to G-CSF monotherapy. Here we tested the
hypothesis whether combinatorial G-CSF/AMD3100 therapy has beneficial effects in
cardiac recovery in a mouse model of myocardial infarction. METHODS: We analyzed
the effect of single G-CSF (250 ug/kg/day) and combinatorial G-CSF/AMD3100 (100
ug/kg/day) treatment on cardiac morphology, vascularization, and hemodynamics 28
days after permanent ligation of the left anterior descending artery (LAD). G-CSF
treatment started directly after induction of myocardial infarction (MI) for 3
consecutive days followed by a single AMD3100 application on day three after MI
in the G-CSF/AMD3100 group. Cell mobilization was assessed by flow cytometry of
blood samples drawn from tail vein on day 0, 7, and 14. RESULTS: Peripheral blood
analysis 7 days after MI showed enhanced mobilization of white blood cells (WBC)
and endothelial progenitor cells (EPC) upon G-CSF and combinatorial G-CSF/AMD3100
treatment. However, single or combinatorial treatment showed no improvement in
survival, left ventricular function, and infarction size compared to the saline
treated control group 28 days after MI. Furthermore, no differences in histology
and vascularization of infarcted hearts could be observed. CONCLUSION: Although
the implemented treatment regimen caused no adverse effects, our data show that
combinatorial G-CSF/AMD therapy does not promote myocardial regeneration after
permanent LAD occlusion.
PMID- 25121740
TI - Microbial-derived butyrate: an oncometabolite or tumor-suppressive metabolite?
AB - Dietary factors, microbial composition, and metabolism are intimately intertwined
into a complex network whose activities influence important intestinal functions.
In a recent issue of Cell, Belcheva et al. (2014) show that microbial-derived
butyrate promotes proliferation of cancer-initiated intestinal epithelial cells,
suggesting that it can act as an oncometabolite.
PMID- 25121739
TI - CXCL12 induces connective tissue growth factor expression in human lung
fibroblasts through the Rac1/ERK, JNK, and AP-1 pathways.
AB - CXCL12 (stromal cell-derived factor-1, SDF-1) is a potent chemokine for homing of
CXCR4+ fibrocytes to injury sites of lung tissue, which contributes to pulmonary
fibrosis. Overexpression of connective tissue growth factor (CTGF) plays a
critical role in pulmonary fibrosis. In this study, we investigated the roles of
Rac1, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK),
and activator protein-1 (AP-1) in CXCL12-induced CTGF expression in human lung
fibroblasts. CXCL12 caused concentration- and time-dependent increases in CTGF
expression and CTGF-luciferase activity. CXCL12-induced CTGF expression was
inhibited by a CXCR4 antagonist (AMD3100), small interfering RNA of CXCR4 (CXCR4
siRNA), a dominant negative mutant of Rac1 (RacN17), a mitogen-activated protein
kinase (MAPK) kinase (MEK) inhibitor (PD98059), a JNK inhibitor (SP600125), a p21
activated kinase inhibitor (PAK18), c-Jun siRNA, and an AP-1 inhibitor
(curcumin). Treatment of cells with CXCL12 caused activations of Rac1, Rho, ERK,
and c-Jun. The CXCL12-induced increase in ERK phosphorylation was inhibited by
RacN17. Treatment of cells with PD98059 and SP600125 both inhibited CXCL12
induced c-Jun phosphorylation. CXCL12 caused the recruitment of c-Jun and c-Fos
binding to the CTGF promoter. Furthermore, CXCL12 induced an increase in alpha
smooth muscle actin (alpha-SMA) expression, a myofibroblastic phenotype, and
actin stress fiber formation. CXCL12-induced actin stress fiber formation and
alpha-SMA expression were respectively inhibited by AMD3100 and CTGF siRNA. Taken
together, our results suggest that CXCL12, acting through CXCR4, activates the
Rac/ERK and JNK signaling pathways, which in turn initiates c-Jun
phosphorylation, and recruits c-Jun and c-Fos to the CTGF promoter and ultimately
induces CTGF expression in human lung fibroblasts. Moreover, overexpression of
CTGF mediates CXCL12-induced alpha-SMA expression.
PMID- 25121741
TI - What lies within: coinfections and immunity.
AB - Helminth-induced immunomodulation is thought to influence the outcome of
secondary infections. Osborne et al. (2014) and Reese et al. (2014) demonstrate
that helminth infection impacts viral infections by tilting the immune system
toward Th2/M2 immune regulatory responses that dampen Th1/M1 antiviral responses
as well as promote reactivation of latent herpesviruses.
PMID- 25121742
TI - Malaria parasite epigenetics: when virulence and romance collide.
AB - Blood-stage malaria parasites evade the immune system by switching the protein
exposed at the surface of the infected erythrocyte. A small proportion of these
parasites commits to sexual development to mediate mosquito transmission. Two
studies in this issue (Brancucci et al., 2014; Coleman et al., 2014) shed light
on shared epigenetic machinery underlying both of these events.
PMID- 25121743
TI - How a virus blocks a cellular emergency access lane to the nucleus, STAT!
AB - Early in viral infection, the STAT1 transcription factor is rapidly transported
into the nucleus using a nonconventional import mechanism to establish an
antiviral state. In this issue, Xu et al. (2014) show how the Ebola virus VP24
protein precisely blocks specialized STAT1 import while leaving other cellular
import processes intact.
PMID- 25121744
TI - Getting rid of the bad apple: inflammasome-induced extrusion of Salmonella
infected enterocytes.
AB - Two reports in this issue of Cell Host & Microbe (Sellin et al., 2014; Knodler et
al., 2014) establish the cell-intrinsic inflammasome-induced extrusion of
infected enterocytes as a general defense mechanism against acute bacterial
infections.
PMID- 25121746
TI - Heterochromatin protein 1 secures survival and transmission of malaria parasites.
AB - Clonally variant expression of surface antigens allows the malaria parasite
Plasmodium falciparum to evade immune recognition during blood stage infection
and secure malaria transmission. We demonstrate that heterochromatin protein 1
(HP1), an evolutionary conserved regulator of heritable gene silencing, controls
expression of numerous P. falciparum virulence genes as well as differentiation
into the sexual forms that transmit to mosquitoes. Conditional depletion of P.
falciparum HP1 (PfHP1) prevents mitotic proliferation of blood stage parasites
and disrupts mutually exclusive expression and antigenic variation of the major
virulence factor PfEMP1. Additionally, PfHP1-dependent regulation of PfAP2-G, a
transcription factor required for gametocyte conversion, controls the switch from
asexual proliferation to sexual differentiation, providing insight into the
epigenetic mechanisms underlying gametocyte commitment. These findings show that
PfHP1 is centrally involved in clonally variant gene expression and sexual
differentiation in P. falciparum and have major implications for developing
antidisease and transmission-blocking interventions against malaria.
PMID- 25121745
TI - Collateral damage: microbiota-derived metabolites and immune function in the
antibiotic era.
AB - Our long-standing evolutionary association with gut-associated microbial
communities has given rise to an intimate relationship, which affects many
aspects of human health. Recent studies on the mechanisms that link these
microbial communities to immune education, nutrition, and protection against
pathogens point to microbiota-derived metabolites as key players during these
microbe-host interactions. A disruption of gut-associated microbial communities
by antibiotic treatment can result in a depletion of microbiota-derived
metabolites, thereby enhancing pathogen susceptibility, impairing immune
homeostasis, and contributing to the rise of certain chronic inflammatory
diseases. Here, we highlight some of the recently elucidated mechanisms that
showcase the impacts of microbiota-derived metabolites on human health.
PMID- 25121747
TI - A Plasmodium falciparum histone deacetylase regulates antigenic variation and
gametocyte conversion.
AB - The asexual forms of the malaria parasite Plasmodium falciparum are adapted for
chronic persistence in human red blood cells, continuously evading host immunity
using epigenetically regulated antigenic variation of virulence-associated genes.
Parasite survival on a population level also requires differentiation into sexual
forms, an obligatory step for further human transmission. We reveal that the
essential nuclear gene, P. falciparum histone deacetylase 2 (PfHda2), is a global
silencer of virulence gene expression and controls the frequency of switching
from the asexual cycle to sexual development. PfHda2 depletion leads to
dysregulated expression of both virulence-associated var genes and PfAP2-g, a
transcription factor controlling sexual conversion, and is accompanied by
increases in gametocytogenesis. Mathematical modeling further indicates that
PfHda2 has likely evolved to optimize the parasite's infectious period by
achieving low frequencies of virulence gene expression switching and sexual
conversion. This common regulation of cellular transcriptional programs
mechanistically links parasite transmissibility and virulence.
PMID- 25121748
TI - Ebola virus VP24 targets a unique NLS binding site on karyopherin alpha 5 to
selectively compete with nuclear import of phosphorylated STAT1.
AB - During antiviral defense, interferon (IFN) signaling triggers nuclear transport
of tyrosine-phosphorylated STAT1 (PY-STAT1), which occurs via a subset of
karyopherin alpha (KPNA) nuclear transporters. Many viruses, including Ebola
virus, actively antagonize STAT1 signaling to counteract the antiviral effects of
IFN. Ebola virus VP24 protein (eVP24) binds KPNA to inhibit PY-STAT1 nuclear
transport and render cells refractory to IFNs. We describe the structure of human
KPNA5 C terminus in complex with eVP24. In the complex, eVP24 recognizes a unique
nonclassical nuclear localization signal (NLS) binding site on KPNA5 that is
necessary for efficient PY-STAT1 nuclear transport. eVP24 binds KPNA5 with very
high affinity to effectively compete with and inhibit PY-STAT1 nuclear transport.
In contrast, eVP24 binding does not affect the transport of classical NLS cargo.
Thus, eVP24 counters cell-intrinsic innate immunity by selectively targeting PY
STAT1 nuclear import while leaving the transport of other cargo that may be
required for viral replication unaffected.
PMID- 25121749
TI - HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of
infected cells.
AB - Immune evasion genes help human cytomegalovirus (HCMV) establish lifelong
persistence. Without immune pressure, laboratory-adapted HCMV strains have
undergone genetic alterations. Among these, the deletion of the UL/b' domain is
associated with loss of virulence. In a screen of UL/b', we identified pUL135 as
a protein responsible for the characteristic cytopathic effect of clinical HCMV
strains that also protected from natural killer (NK) and T cell attack. pUL135
interacted directly with abl interactor 1 (ABI1) and ABI2 to recruit the WAVE2
regulatory complex to the plasma membrane, remodel the actin cytoskeleton and
dramatically reduce the efficiency of immune synapse (IS) formation. An intimate
association between F-actin filaments in target cells and the IS was dispelled by
pUL135 expression. Thus, F-actin in target cells plays a critical role in
synaptogenesis, and this can be exploited by pathogens to protect against
cytotoxic immune effector cells. An independent interaction between pUL135 and
talin disrupted cell contacts with the extracellular matrix.
PMID- 25121750
TI - HIV-1 envelope gp41 antibodies can originate from terminal ileum B cells that
share cross-reactivity with commensal bacteria.
AB - Monoclonal antibodies derived from blood plasma cells of acute HIV-1-infected
individuals are predominantly targeted to the HIV Env gp41 and cross-reactive
with commensal bacteria. To understand this phenomenon, we examined anti-HIV
responses in ileum B cells using recombinant antibody technology and probed their
relationship to commensal bacteria. The dominant ileum B cell response was to Env
gp41. Remarkably, a majority (82%) of the ileum anti-gp41 antibodies cross
reacted with commensal bacteria, and of those, 43% showed non-HIV-1 antigen
polyreactivity. Pyrosequencing revealed shared HIV-1 antibody clonal lineages
between ileum and blood. Mutated immunoglobulin G antibodies cross-reactive with
both Env gp41 and microbiota could also be isolated from the ileum of HIV-1
uninfected individuals. Thus, the gp41 commensal bacterial antigen cross-reactive
antibodies originate in the intestine, and the gp41 Env response in HIV-1
infection can be derived from a preinfection memory B cell pool triggered by
commensal bacteria that cross-react with Env.
PMID- 25121751
TI - Epithelium-intrinsic NAIP/NLRC4 inflammasome drives infected enterocyte expulsion
to restrict Salmonella replication in the intestinal mucosa.
AB - The gut mucosal epithelium separates the host from the microbiota, but
enteropathogens such as Salmonella Typhimurium (S.Tm) can invade and breach this
barrier. Defenses against such acute insults remain incompletely understood.
Using a murine model of Salmonella enterocolitis, we analyzed mechanisms limiting
pathogen loads in the epithelium during early infection. Although the epithelium
invading S.Tm replicate initially, this intraepithelial replicative niche is
restricted by expulsion of infected enterocytes into the lumen. This mechanism is
compromised if inflammasome components (NAIP1-6, NLRC4, caspase-1/-11) are
deleted, or ablated specifically in the epithelium, resulting in ~100-fold higher
intraepithelial loads and accelerated lymph node colonization. Interestingly, the
cytokines downstream of inflammasome activation, interleukin (IL)-1alpha/beta and
IL-18, appear dispensable for epithelial restriction of early infection. These
data establish the role of an epithelium-intrinsic inflammasome, which drives
expulsion of infected cells to restrict the pathogen's intraepithelial
proliferation. This may represent a general defense mechanism against mucosal
infections.
PMID- 25121754
TI - Assessment of the relationship between nondipping phenomenon and microvolt T-wave
alternans.
AB - OBJECTIVE: The aim of this cross-sectional study was to evaluate microvolt T-wave
alternans (MTWA) as a marker of myocardial electrical instability in normotensive
and hypertensive individuals with either nondipper or dipper-type circadian
rhythm of blood pressure. MATERIALS AND METHODS: The study group included a total
of 181 patients: 118 hypertensive patients and 63 normotensive healthy volunteers
[mean age 46 +/- 8; 34 men (54%)]. The patients with hypertension were divided
into two groups on the basis of their results of 24-h ambulatory blood pressure
monitoring: 61 patients with dipper hypertension [mean age 46 +/- 6; 32 men
(52.5%)] and 57 patients with nondipper hypertension [mean age 48 +/- 10; 36 men
(63.2%)]. The MTWAs of all patients were analyzed using the time-domain modified
moving average method by means of a treadmill exercise stress test. RESULTS: MTWA
positivity was statistically significantly different between all groups. Left
ventricular mass index, E/E', interventricular septum, posterior wall, 24-h
systolic blood pressure and diastolic blood pressure, and night-time systolic
blood pressure and diastolic blood pressure were correlated positively with MTWA.
Left ventricular mass index and the presence of nondipper hypertension were
determined to be independent predictors of MTWA positivity. CONCLUSION: The
blunting of the nocturnal decrease in blood pressure was associated with MTWA
positivity in hypertensive patients.
PMID- 25121753
TI - Hepatitis C virus subverts liver-specific miR-122 to protect the viral genome
from exoribonuclease Xrn2.
AB - The abundant, liver-specific microRNA miR-122 forms extensive base-pairing
interactions with the 5' noncoding region of the hepatitis C virus (HCV) RNA
genome, protecting the viral RNA from degradation. We discovered that the 5'-3'
exoribonuclease Xrn2, which plays a crucial role in the transcription termination
of RNA polymerase II, modulates HCV RNA abundance in the cytoplasm, but is
counteracted by miR-122-mediated protection. Specifically, Xrn2 depletion results
in increased accumulation of viral RNA, while Xrn2 overexpression diminishes
viral RNA abundance. Depletion of Xrn2 did not alter translation or replication
rates of HCV RNA, but affected viral RNA stability. Importantly, during
sequestration of miR-122, Xrn2 depletion restored HCV RNA abundance, arguing that
Xrn2 depletion eliminates the miR-122 requirement for viral RNA stability. Thus,
Xrn2 has a cytoplasmic, antiviral function against HCV that is counteracted by
HCV's subversion of miR-122 to form a protective oligomeric complex at the 5' end
of the viral genome.
PMID- 25121752
TI - Noncanonical inflammasome activation of caspase-4/caspase-11 mediates epithelial
defenses against enteric bacterial pathogens.
AB - Inflammasome-mediated host defenses have been extensively studied in innate
immune cells. Whether inflammasomes function for innate defense in intestinal
epithelial cells, which represent the first line of defense against enteric
pathogens, remains unknown. We observed enhanced Salmonella enterica serovar
Typhimurium colonization in the intestinal epithelium of caspase-11-deficient
mice, but not at systemic sites. In polarized epithelial monolayers, siRNA
mediated depletion of caspase-4, a human ortholog of caspase-11, also led to
increased bacterial colonization. Decreased rates of pyroptotic cell death, a
host defense mechanism that extrudes S. Typhimurium-infected cells from the
polarized epithelium, accounted for increased pathogen burdens. The caspase-4
inflammasome also governs activation of the proinflammatory cytokine, interleukin
(IL)-18, in response to intracellular (S. Typhimurium) and extracellular
(enteropathogenic Escherichia coli) enteric pathogens, via intracellular LPS
sensing. Therefore, an epithelial cell-intrinsic noncanonical inflammasome plays
a critical role in antimicrobial defense at the intestinal mucosal surface.
PMID- 25121755
TI - The effect of orthostatic stress type on cardiovascular control.
AB - OBJECTIVES: We aimed to compare the cardiovascular responses of a novel
orthostatic stress test, the passive seated orthostatic stress test (PSOST), with
those during passive head-up tilt testing (HUTT). We hypothesized that
cardiovascular responses during PSOST would be similar to those during HUTT (the
'gold standard'). METHODS: We tested 15 healthy volunteers, who underwent both
PSOST and HUTT during one session in a random order. We measured beat-to-beat
blood pressure, heart rate, peripheral resistance, stroke volume, cardiac output,
and middle cerebral artery blood flow velocity during each test. RESULTS: Blood
pressure responses were not significantly different between PSOST and HUTT,
except for a significantly lower delayed nadir and 15-min recovery value in
systolic arterial pressure during HUTT. HUTT elicited a significantly larger
increase in heart rate during all test intervals in comparison with PSOST, as
well as a larger decline in stroke volume during almost all test intervals.
Responses for the other hemodynamic variables were not significantly different
between the tests at any test interval. Repeated HUTT has large inherent
variability, which was also evident from the variability in the mean differences
on comparing PSOST and HUTT. There was a significant bias for larger heart rate
increases (P<0.01) and a greater delayed systolic arterial pressure decline
during HUTT. CONCLUSION: We have shown that PSOST and HUTT elicit similar blood
pressure and cerebrovascular responses in the early stages of the upright phase.
We believe that PSOST is a reasonable surrogate for HUTT in assessing orthostatic
hypotension in population groups that are unable to stand for prolonged periods
of time.
PMID- 25121756
TI - Neck circumference and body mass index as independent predictors of hypertension
misclassification in patients suspected of having obstructive sleep apnea.
AB - OBJECTIVE(S): Twenty-four-hour ambulatory blood pressure monitoring (ABPM) seems
to be the most accurate way of diagnosing hypertension in patients with
obstructive sleep apnea (OSA). However, this diagnostic tool is expensive and
time-consuming and is therefore not used routinely. We aimed to find baseline
predictors that enable the identification of patients who misclassify themselves
as nonhypertensive to optimize the use of ABPM. METHODS: Clinically suspected OSA
patients (n=369) were enrolled and underwent overnight polysomnography and 24-h
ABPM, and completed a data collection form. Anthropometric measurements were
assessed. Generalized additive models, the minimum P-value approach, and logistic
regression models were used for data analysis. Results were considered
significant when alpha is equal to 0.05. RESULTS: One hundred and twenty-two
patients who were not on antihypertensive medication did not report hypertension,
but according to ABPM data, 43.4% (n=53) of them had misclassified themselves as
nonhypertensive. These patients had a significantly higher apnea-hypopnea index
(P<0.001), ABPM variables (P<0.001), BMI (P=0.002), and neck circumference (NC)
(P=0.002) than nonhypertensive patients (n=69). BMI and NC emerged as independent
predictors of hypertension misclassification. The cut-off points that best
discriminated the two groups of patients were 27 kg/m and 39 cm for BMI and NC,
respectively. The resulting binary BMI and NC remained independent predictors of
hypertension misclassification in the final model (odds ratio: 3.2, P=0.010; odds
ratio: 2.4, P=0.038). CONCLUSION: Our findings emphasize the importance of ABPM
for the diagnosis of hypertension in patients suspected of having OSA with a BMI
and NC above 27 kg/m and 39 cm, respectively.
PMID- 25121757
TI - Transcriptome sequencing from diverse human populations reveals differentiated
regulatory architecture.
AB - Large-scale sequencing efforts have documented extensive genetic variation within
the human genome. However, our understanding of the origins, global distribution,
and functional consequences of this variation is far from complete. While
regulatory variation influencing gene expression has been studied within a
handful of populations, the breadth of transcriptome differences across diverse
human populations has not been systematically analyzed. To better understand the
spectrum of gene expression variation, alternative splicing, and the population
genetics of regulatory variation in humans, we have sequenced the genomes,
exomes, and transcriptomes of EBV transformed lymphoblastoid cell lines derived
from 45 individuals in the Human Genome Diversity Panel (HGDP). The populations
sampled span the geographic breadth of human migration history and include
Namibian San, Mbuti Pygmies of the Democratic Republic of Congo, Algerian
Mozabites, Pathan of Pakistan, Cambodians of East Asia, Yakut of Siberia, and
Mayans of Mexico. We discover that approximately 25.0% of the variation in gene
expression found amongst individuals can be attributed to population differences.
However, we find few genes that are systematically differentially expressed among
populations. Of this population-specific variation, 75.5% is due to expression
rather than splicing variability, and we find few genes with strong evidence for
differential splicing across populations. Allelic expression analyses indicate
that previously mapped common regulatory variants identified in eight populations
from the International Haplotype Map Phase 3 project have similar effects in our
seven sampled HGDP populations, suggesting that the cellular effects of common
variants are shared across diverse populations. Together, these results provide a
resource for studies analyzing functional differences across populations by
estimating the degree of shared gene expression, alternative splicing, and
regulatory genetics across populations from the broadest points of human
migration history yet sampled.
PMID- 25121758
TI - Age and sex-specific relationships between phthalate exposures and obesity in
Chinese children at puberty.
AB - OBJECTIVE: To examine the age and sex-specific associations of urine levels of
six mono-phthalates with body size and fat distribution in Chinese children at
puberty. MATERIALS AND METHODS: Four hundred and ninety-three school-aged
children (247 boys, 246 girls) were recruited. Obesity related anthropometric
indices were measured and body fat proportion (BF%) was calculated. Spot urine
samples were collected and phthalate monoesters were detected by an API 2000
electrospray triple quadrupole mass spectrometer (ESI-MS/MS). Associations
between phthalate exposure and overweight/obesity measures and their trends were
examined by multiple linear regression and Logistic regression analyses,
respectively. RESULTS: Di-2-ethylhexyl phthalate (DEHP) metabolites and monobutyl
phthalate (MBP) were found to be the most detectable chemicals. In 8-10 years
(yrs) group, concentrations of MEHP and MBP were significantly higher in girls
than those in boys. However, concentrations of all phthalate monoesters, except
for MEP and MEHP, in 11-13 yrs boys were significantly higher than those in
girls. After adjusting for confounders including puberty onset, urinary
concentrations of MBP and sum of low molecular-weight phthalate metabolites
(?LMP) were positively associated with boys' obesity in a concentration-effect
manner, while concentrations of MEHP, MEHHP and sum of DEHP metabolites (?MEHP)
were negatively associated with girls' obesity. Associations between phthalate
exposure levels and BMI z-score changes were age- and sex-specific in school-age
children. CONCLUSION: There are age and sex-specific concentration-effect
associations between phthalate exposure and fat distribution in Chinese children.
Urinary phthalate levels in 11-13 yrs boys were about 30 percent higher than
those in girls, and ?MEHP levels in younger boys (<10 yrs) were significantly
higher than those in elder boys (>10 yrs). Associations were positive for MBP and
?LMP with both BMI z-score and fat distribution in boys >10 years of age, and
negative for ?MEHP with fat distribution in girls <10 years of age.
PMID- 25121759
TI - Primary amoebic meningoencephalitis caused by Naegleria fowleri: an old enemy
presenting new challenges.
AB - First discovered in 1899, Naegleria fowleri is a protist pathogen, known to
infect the central nervous system and produce primary amoebic
meningoencephalitis. The most distressing aspect is that the fatality rate has
remained more than 95%, despite our advances in antimicrobial chemotherapy and
supportive care. Although rare worldwide, most cases have been reported in the
United States, Australia, and Europe (France). A large number of cases in
developing countries go unnoticed. In particular, religious, recreational, and
cultural practices such as ritual ablution and/or purifications, Ayurveda, and
the use of neti pots for nasal irrigation can contribute to this devastating
infection. With increasing water scarcity and public reliance on water storage,
here we debate the need for increased awareness of primary amoebic
meningoencephalitis and the associated risk factors, particularly in developing
countries.
PMID- 25121760
TI - The rich get richer: brain injury elicits hyperconnectivity in core subnetworks.
AB - There remains much unknown about how large-scale neural networks accommodate
neurological disruption, such as moderate and severe traumatic brain injury
(TBI). A primary goal in this study was to examine the alterations in network
topology occurring during the first year of recovery following TBI. To do so we
examined 21 individuals with moderate and severe TBI at 3 and 6 months after
resolution of posttraumatic amnesia and 15 age- and education-matched healthy
adults using functional MRI and graph theoretical analyses. There were two
central hypotheses in this study: 1) physical disruption results in increased
functional connectivity, or hyperconnectivity, and 2) hyperconnectivity occurs in
regions typically observed to be the most highly connected cortical hubs, or the
"rich club". The current findings generally support the hyperconnectivity
hypothesis showing that during the first year of recovery after TBI, neural
networks show increased connectivity, and this change is disproportionately
represented in brain regions belonging to the brain's core subnetworks. The
selective increases in connectivity observed here are consistent with the
preferential attachment model underlying scale-free network development. This
study is the largest of its kind and provides the unique opportunity to examine
how neural systems adapt to significant neurological disruption during the first
year after injury.
PMID- 25121761
TI - Isolation of cancer stem cells from three human glioblastoma cell lines:
characterization of two selected clones.
AB - Cancer stem cells (CSC) were isolated via a non-adherent neurosphere assay from
three glioma cell lines: LI, U87, and U373. Using a clonal assay, two clones (D2
and F11) were selected from spheres derived from LI cells and were characterized
for the: expression of stem cell markers (CD133, Nestin, Musashi-1 and Sox2);
proliferation; differentiation capability (determined by the expression of GalC,
betaIII-Tubulin and GFAP); Ca(2+) signaling and tumorigenicity in nude mice. Both
D2 and F11 clones expressed higher levels of all stem cell markers with respect
to the parental cell line. Clones grew more slowly than LI cells with a two-fold
increase in duplication time. Markers of differentiation (betaIII-Tubulin and
GFAP) were expressed at high levels in both LI cells and in neurospheres. The
expression of Nestin, Sox2, and betaIII-Tubulin was down-regulated in D2 and F11
when cultured in serum-containing medium, whereas Musashi-1 was increased. In
this condition, duplication time of D2 and F11 increased without reaching that of
LI cells. D2, F11 and parental cells did not express voltage-dependent Ca(2+)
channels but they exhibited increased intracellular Ca(2+) levels in response to
ATP. These Ca(2+) signals were larger in LI cells and in spheres cultured in
serum-containing medium, while they were smaller in serum-free medium. The ATP
treatment did not affect cell proliferation. Both D2 and F11 induced the
appearance of tumors when ortotopically injected in athymic nude mice at a
density 50-fold lower than that of LI cells. All these data indicate that both
clones have characteristics of CSC and share the same stemness properties. The
findings regarding the expression of differentiation markers and Ca(2+)-channels
show that both clones are unable to reach the terminal differentiation. Both D2
and F11 might represent a good model to improve the knowledge on CSC in
glioblastoma and to identify new therapeutic approaches.
PMID- 25121762
TI - Unveiling time in dose-response models to infer host susceptibility to pathogens.
AB - The biological effects of interventions to control infectious diseases typically
depend on the intensity of pathogen challenge. As much as the levels of natural
pathogen circulation vary over time and geographical location, the development of
invariant efficacy measures is of major importance, even if only indirectly
inferrable. Here a method is introduced to assess host susceptibility to
pathogens, and applied to a detailed dataset generated by challenging groups of
insect hosts (Drosophila melanogaster) with a range of pathogen (Drosophila C
Virus) doses and recording survival over time. The experiment was replicated for
flies carrying the Wolbachia symbiont, which is known to reduce host
susceptibility to viral infections. The entire dataset is fitted by a novel
quantitative framework that significantly extends classical methods for microbial
risk assessment and provides accurate distributions of symbiont-induced
protection. More generally, our data-driven modeling procedure provides novel
insights for study design and analyses to assess interventions.
PMID- 25121763
TI - Genetic diversity and structure of Dalmatian pyrethrum (Tanacetum cinerariifolium
Trevir./Sch./Bip., Asteraceae) within the Balkan refugium.
AB - Dalmatian pyrethrum (Tanacetum cinerariifolium Trevir./Sch./Bip.) is an
outcrossing, perennial insecticidal plant, restricted to the eastern Adriatic
coast (Mediterranean). Amplified fragment-length polymorphisms (AFLP) were used
to investigate the genetic diversity and structure within and among 20 natural
plant populations. The highest level of gene diversity, the number of private
alleles and the frequency down-weighted marker values (DW) were found in northern
Adriatic populations and gradually decreased towards the southern boundary of the
species range. Genetic impoverishment of these southern populations is most
likely the result of human-related activities. An analysis of molecular variance
(AMOVA) indicated that most of the genetic diversity was attributed to
differences among individuals within populations (85.78%), which are expected due
to the outcrossing nature of the species. A Bayesian analysis of the population
structure identified two dominant genetic clusters. A spatial analysis of the
genetic diversity indicated that 5.6% of the genetic differentiation resulted
from isolation by distance (IBD), while 12.3% of the genetic differentiation
among populations followed the pattern of isolation by environmental distance
(IBED). Knowledge of the genetic diversity patterns of the natural populations
and the mechanism behind these patterns is required for the exploitation and
possible conservation management of this endemic and economically important
species.
PMID- 25121766
TI - A deterministic model predicts the properties of stochastic calcium oscillations
in airway smooth muscle cells.
AB - The inositol trisphosphate receptor ([Formula: see text]) is one of the most
important cellular components responsible for oscillations in the cytoplasmic
calcium concentration. Over the past decade, two major questions about the
[Formula: see text] have arisen. Firstly, how best should the [Formula: see text]
be modeled? In other words, what fundamental properties of the [Formula: see
text] allow it to perform its function, and what are their quantitative
properties? Secondly, although calcium oscillations are caused by the stochastic
opening and closing of small numbers of [Formula: see text], is it possible for a
deterministic model to be a reliable predictor of calcium behavior? Here, we
answer these two questions, using airway smooth muscle cells (ASMC) as a specific
example. Firstly, we show that periodic calcium waves in ASMC, as well as the
statistics of calcium puffs in other cell types, can be quantitatively reproduced
by a two-state model of the [Formula: see text], and thus the behavior of the
[Formula: see text] is essentially determined by its modal structure. The
structure within each mode is irrelevant for function. Secondly, we show that,
although calcium waves in ASMC are generated by a stochastic mechanism, [Formula:
see text] stochasticity is not essential for a qualitative prediction of how
oscillation frequency depends on model parameters, and thus deterministic
[Formula: see text] models demonstrate the same level of predictive capability as
do stochastic models. We conclude that, firstly, calcium dynamics can be
accurately modeled using simplified [Formula: see text] models, and, secondly, to
obtain qualitative predictions of how oscillation frequency depends on parameters
it is sufficient to use a deterministic model.
PMID- 25121765
TI - Mobility and generation of mosaic non-autonomous transposons by Tn3-derived
inverted-repeat miniature elements (TIMEs).
AB - Functional transposable elements (TEs) of several Pseudomonas spp. strains
isolated from black shale ore of Lubin mine and from post-flotation tailings of
Zelazny Most in Poland, were identified using a positive selection trap plasmid
strategy. This approach led to the capture and characterization of (i) 13
insertion sequences from 5 IS families (IS3, IS5, ISL3, IS30 and IS1380), (ii)
isoforms of two Tn3-family transposons--Tn5563a and Tn4662a (the latter contains
a toxin-antitoxin system), as well as (iii) non-autonomous TEs of diverse
structure, ranging in size from 262 to 3892 bp. The non-autonomous elements
transposed into AT-rich DNA regions and generated 5- or 6-bp sequence
duplications at the target site of transposition. Although these TEs lack a
transposase gene, they contain homologous 38-bp-long terminal inverted repeat
sequences (IRs), highly conserved in Tn5563a and many other Tn3-family
transposons. The simplest elements of this type, designated TIMEs (Tn3 family
derived Inverted-repeat Miniature Elements) (262 bp), were identified within two
natural plasmids (pZM1P1 and pLM8P2) of Pseudomonas spp. It was demonstrated that
TIMEs are able to mobilize segments of plasmid DNA for transposition, which
results in the generation of more complex non-autonomous elements, resembling IS
driven composite transposons in structure. Such transposon-like elements may
contain different functional genetic modules in their core regions, including
plasmid replication systems. Another non-autonomous element "captured" with a
trap plasmid was a TIME derivative containing a predicted resolvase gene and a
res site typical for many Tn3-family transposons. The identification of a
portable site-specific recombination system is another intriguing example
confirming the important role of non-autonomous TEs of the TIME family in
shuffling genetic information in bacterial genomes. Transposition of such mosaic
elements may have a significant impact on diversity and evolution, not only of
transposons and plasmids, but also of other types of mobile genetic elements.
PMID- 25121768
TI - Metabolome analysis of Drosophila melanogaster during embryogenesis.
AB - The Drosophila melanogaster embryo has been widely utilized as a model for
genetics and developmental biology due to its small size, short generation time,
and large brood size. Information on embryonic metabolism during developmental
progression is important for further understanding the mechanisms of Drosophila
embryogenesis. Therefore, the aim of this study is to assess the changes in
embryos' metabolome that occur at different stages of the Drosophila embryonic
development. Time course samples of Drosophila embryos were subjected to GC/MS
based metabolome analysis for profiling of low molecular weight hydrophilic
metabolites, including sugars, amino acids, and organic acids. The results showed
that the metabolic profiles of Drosophila embryo varied during the course of
development and there was a strong correlation between the metabolome and
different embryonic stages. Using the metabolome information, we were able to
establish a prediction model for developmental stages of embryos starting from
their high-resolution quantitative metabolite composition. Among the important
metabolites revealed from our model, we suggest that different amino acids appear
to play distinct roles in different developmental stages and an appropriate
balance in trehalose-glucose ratio is crucial to supply the carbohydrate source
for the development of Drosophila embryo.
PMID- 25121767
TI - Bone morphogenetic protein 6 polymorphisms are associated with radiographic
progression in ankylosing spondylitis.
AB - BACKGROUND AND OBJECT: Nearly 25 genetic loci associated with susceptibility to
ankylosing spondylitis (AS) have been identified by several large studies.
However, there have been limited studies to identify the genes associated with
radiographic severity of the disease. Thus we investigated which genes involved
in bone formation pathways might be associated with radiographic severity in AS.
METHODS: A total of 417 Korean AS patients were classified into two groups based
on the radiographic severity as defined by the modified Stoke' Ankylosing
Spondylitis Spinal Score (mSASSS) system. Severe AS was defined by the presence
of syndesmophytes and/or fusion in the lumbar or cervical spine (n = 195). Mild
AS was defined by the absence of any syndesmophyte or fusion (n = 170). A total
of 251 single nucleotide polymorphisms (SNPs) within 52 genes related to bone
formation were selected and genotyped. Odds ratios (OR) and 95% confidence
interval (95% CI) were analysed by multivariate logistic regression controlling
for age at onset of symptoms, sex, disease duration, and smoking status as
covariates. RESULTS: We identified new loci of bone morphogenetic protein 6
(BMP6) associated with radiographic severity in patients with AS that passed
false discovery rate threshold. Two SNPs in BMP6 were significantly associated
with radiologic severity [rs270378 (OR 1.97, p = 6.74 * 10(-4)) and rs1235192 [OR
1.92, p = 1.17 * 10(-3)]) adjusted by covariates. CONCLUSION: This is the first
study to demonstrate that BMP6 is associated with radiographic severity in AS,
supporting the role wingless-type like/BMP pathway on radiographic progression in
AS.
PMID- 25121769
TI - Adjuvant and salvage radiotherapy after prostatectomy: a systematic review and
meta-analysis.
AB - PURPOSE: In men with adverse prognostic factors (APFs) after radical
prostatectomy (RP), the most appropriate timing to administer radiotherapy
remains a subject for debate. We conducted a systemic review and meta-analysis to
evaluate the therapeutic strategies: adjuvant radiotherapy (ART) and salvage
radiotherapy (SRT). MATERIALS AND METHODS: We comprehensively searched PubMed,
EMBASE, Web of Science and the Cochrane Library and performed the meta-analysis
of all randomized controlled trials (RCTs) and retrospective comparative studies
assessing the prognostic factors of ART and SRT. RESULTS: Between May 1998 and
July 2012, 2 matched control studies and 16 retrospective studies including a
total of 2629 cases were identified (1404 cases for ART and 1185 cases for SRT).
5-year biochemical failure free survival (BFFS) for ART was longer than that for
SRT (Hazard Ratio [HR]: 0.37; 95% CI, 0.30-0.46; p<0.00001, I(2) = 0%). 3-year
BFFS was significantly longer in the ART (HR: 0.38; 95% CI, 0.28-0.52; p<0.00001,
I(2) = 0%). Overall survival (OS) was also better in the ART (RR: 0.53; 95% CI,
0.41-0.68; p<0.00001, I(2) = 0%), as did disease free survival (DFS) (RR: 0.53;
95% CI, 0.43-0.66; p<0.00001, I(2) = 0%). Exploratory subgroup analysis and
sensitivity analysis revealed the similar results with original analysis.
CONCLUSION: ART therapy offers a safe and efficient alternative to SRT with
longer 3-year and 5-year BFFS, better OS and DFS. Our recommendation is to
suggest ART for patients with APFs and may reduce the need for SRT. Given the
inherent limitations of the included studies, future well-designed RCTs are
awaited to confirm and update this analysis.
PMID- 25121764
TI - Helicobacter pylori from gastric cancer and duodenal ulcer show same
phylogeographic origin in the Andean region in Colombia.
AB - BACKGROUND: A recent report has shown that the phylogenetic origin of
Helicobacter pylori based on multi-locus sequence typing (MLST) was significantly
associated with the severity of gastritis in Colombia. However, the potential
relationship between phylogenetic origin and clinical outcomes was not examined
in that study. If the phylogenetic origin rather than virulence factors were
truly associated with clinical outcomes, identifying a population at high risk
for gastric cancer in Colombia would be relatively straightforward. In this
study, we examined the phylogenetic origins of strains from gastric cancer and
duodenal ulcer patients living in Bogota, Colombia. METHODS: We included 35
gastric cancer patients and 31 duodenal ulcer patients, which are considered the
variant outcomes. The genotypes of cagA and vacA were determined by polymerase
chain reaction. The genealogy of these Colombian strains was analyzed by MLST.
Bacterial population structure was analyzed using STRUCTURE software. RESULTS: H.
pylori strains from gastric cancer and duodenal ulcer patients were scattered in
the phylogenetic tree; thus, we did not detect any difference in phylogenetic
distribution between gastric cancer and duodenal ulcer strains in the hpEurope
group in Colombia. Sixty-six strains, with one exception, were classified as
hpEurope irrespective of the cagA and vacA genotypes, and type of disease.
STRUCTURE analysis revealed that Colombian hpEurope strains have a phylogenetic
connection to Spanish strains. CONCLUSIONS: Our study showed that a
phylogeographic origin determined by MLST was insufficient for distinguishing
between gastric cancer and duodenal ulcer risk among hpEurope strains in the
Andean region in Colombia. Our analysis also suggests that hpEurope strains in
Colombia were primarily introduced by Spanish immigrants.
PMID- 25121771
TI - Brain tumor classification using the diffusion tensor image segmentation (D-SEG)
technique.
AB - BACKGROUND: There is an increasing demand for noninvasive brain tumor biomarkers
to guide surgery and subsequent oncotherapy. We present a novel whole-brain
diffusion tensor imaging (DTI) segmentation (D-SEG) to delineate tumor volumes of
interest (VOIs) for subsequent classification of tumor type. D-SEG uses isotropic
(p) and anisotropic (q) components of the diffusion tensor to segment regions
with similar diffusion characteristics. METHODS: DTI scans were acquired from 95
patients with low- and high-grade glioma, metastases, and meningioma and from 29
healthy subjects. D-SEG uses k-means clustering of the 2D (p,q) space to generate
segments with different isotropic and anisotropic diffusion characteristics.
RESULTS: Our results are visualized using a novel RGB color scheme incorporating
p, q and T2-weighted information within each segment. The volumetric contribution
of each segment to gray matter, white matter, and cerebrospinal fluid spaces was
used to generate healthy tissue D-SEG spectra. Tumor VOIs were extracted using a
semiautomated flood-filling technique and D-SEG spectra were computed within the
VOI. Classification of tumor type using D-SEG spectra was performed using support
vector machines. D-SEG was computationally fast and stable and delineated regions
of healthy tissue from tumor and edema. D-SEG spectra were consistent for each
tumor type, with constituent diffusion characteristics potentially reflecting
regional differences in tissue microstructure. Support vector machines classified
tumor type with an overall accuracy of 94.7%, providing better classification
than previously reported. CONCLUSIONS: D-SEG presents a user-friendly,
semiautomated biomarker that may provide a valuable adjunct in noninvasive brain
tumor diagnosis and treatment planning.
PMID- 25121772
TI - Hell's BELs: bacterial E3 ligases that exploit the eukaryotic ubiquitin
machinery.
PMID- 25121770
TI - Clinical course and progression-free survival of adult intracranial and spinal
ependymoma patients.
AB - BACKGROUND: Ependymomas are rare CNS tumors. Previous studies describing the
clinical course of ependymoma patients were restricted to small sample sizes,
often with patients at a specific institution. METHODS: Clinically annotated
ependymoma tissue samples from 19 institutions were centrally reviewed. Patients
were all adults aged 18 years or older at the time of diagnosis. Potential
prognostic clinical factors identified on univariate analysis were included in a
multivariate Cox proportional hazards model with backwards selection to model
progression-free survival. RESULTS: The 282 adult ependymoma patients were
equally male and female with a mean age of 43 years (range, 18-80y) at diagnosis.
The majority were grade II (78%) with the tumor grade for 20 cases being
reclassified on central review (half to higher grade). Tumor locations were spine
(46%), infratentorial (35%), and supratentorial (19%). Tumor recurrence occurred
in 26% (n = 74) of patients with a median time to progression of 14 years. A
multivariate Cox proportional hazards model identified supratentorial location (P
< .01), grade III (anaplastic; P < .01), and subtotal resection, followed or not
by radiation (P < .01), as significantly increasing risk of early progression.
CONCLUSIONS: We report findings from an ongoing, multicenter collaboration from a
collection of clinically annotated adult ependymoma tumor samples demonstrating
distinct predictors of progression-free survival. This unique resource provides
the opportunity to better define the clinical course of ependymoma for clinical
and translational studies.
PMID- 25121773
TI - Effects of aprepitant on the pharmacokinetics of controlled-release oral
oxycodone in cancer patients.
AB - PURPOSE: Oxycodone is a u-opioid receptor agonist widely used in the treatment of
cancer pain. The predominant metabolic pathway of oxycodone is CYP3A4-mediated N
demethylation to noroxycodone, while a minor proportion undergoes 3-O
demethylation to oxymorphone by CYP2D6. The aim of this study was to investigate
the effects of the mild CYP3A4 inhibitor aprepitant on the pharmacokinetics of
orally administered controlled-release (CR) oxycodone. METHOD: This study design
was an open-label, single-sequence with two phases in cancer patients with pain
who continued to be administered orally with multiple doses of CR oxycodone every
8 or 12 hours. Plasma concentration of oxycodone and its metabolites were
measured up to 8 hours after administration as follows: on day 1, CR oxycodone
was administered alone; on day 2, CR oxycodone was administered with aprepitant
(125 mg, at the same time of oxycodone dosing in the morning). The steady-state
trough concentrations (Css) were measured from day 1 to day 3. RESULTS:
Aprepitant increased the area under the plasma concentration-time curve (AUC0-8)
of oxycodone by 25% (p<0.001) and of oxymorphone by 34% (p<0.001), as well as
decreased the AUC0-8 of noroxycodone by 14% (p<0.001). Moreover, aprepitant
increased Css of oxycodone by 57% (p = 0.001) and of oxymorphone by 36% (p<0.001)
and decreased Css of noroxycodone by 24% (p = 0.02) at day 3 compared to day 1.
CONCLUSIONS: The clinical use of aprepitant in patients receiving multiple doses
of CR oxycodone for cancer pain significantly altered plasma concentration
levels, but would not appear to need modification of the CR oxycodone dose. TRIAL
REGISTRATION: UMIN.ac.jp UMIN000003580.
PMID- 25121774
TI - Impact of propofol anaesthesia on cytokine expression profiles in the developing
rat brain: a randomised placebo-controlled experimental in-vivo study.
AB - BACKGROUND: Recent experimental data indicate that volatile anaesthetics can
induce a neuroinflammatory response in the central nervous system. The questions
of to what extent this occurs in the developing brain and whether nonvolatile
anaesthetics are also involved remain unanswered. OBJECTIVES: The objective of
this study is to investigate the impact of propofol anaesthesia on cytokine mRNA
expression profiles in the neonatal brain at defined stages of the brain growth
spurt. DESIGN: A randomised placebo-controlled experimental in-vivo study.
SETTING: Translational research laboratories at the University of Geneva Medical
School. METHODS: Wistar rats received 6-h propofol anaesthesia at postnatal day
10 or 20. A quantitative real-time PCR was used to evaluate the impact of this
treatment paradigm on mRNA expression profiles of selected members of the
cytokine family in the prefrontal cortex and hippocampus. RESULTS: Propofol
anaesthesia induced a transient 1.8-fold (interquartile range, IQR 1.7 to 2.2)
increase (P = 0.004) in prefrontal but not hippocampal tumour necrosis factor
mRNA concentrations in 10-day-old animals. No such effect was detected in 20-day
old animals. No changes in mRNA concentrations of two other pro-inflammatory
cytokines, interleukins IL-6 and IL-1beta, were detected following drug exposure
at any developmental stages or in any studied brain regions. In contrast,
propofol anaesthesia at postnatal day 10 induced a transient increase in the mRNA
expression patterns of two chemokines: Ccl2 and Ccl3 [for Ccl2 mRNA: 4.4-fold
(3.8 to 5.6) increase in the prefrontal cortex, P = 0.0002 and a 3.5-fold (2.8 to
5.3) increase in the hippocampus, P = 0.0001; for Ccl3 mRNA: 2.9-fold (2.6 to
4.31) increase in the prefrontal cortex, P = 0.0001, and a 2.7-fold (2.2 to 3.6)
increase in the hippocampus, P = 0.0003]. Propofol did not affect Ccl2 and Ccl3
mRNA concentrations in 20-day-old animals. In addition, it did not impact on two
other members of the chemokine family, Cxcl1 and Cx3cl1, at any time points or in
any brain regions investigated. CONCLUSION: This study suggests that propofol
anaesthesia does not have a major impact on pro-inflammatory cytokine expression
profiles in the developing central nervous system during the brain growth spurt.
These results raise arguments against the involvement of neuroinflammatory
pathways in propofol-related neurotoxicity observed following the administration
of this drug in the early postnatal period.
PMID- 25121775
TI - Mortality in patients with AIDS-related cytomegalovirus retinitis in Myanmar.
PMID- 25121777
TI - Effect of human immunodeficiency virus infection on plasma bactericidal activity
against Salmonella enterica serovar Typhimurium.
AB - Individuals with human immunodeficiency virus (HIV) infection have increased
susceptibility to invasive disease caused by Salmonella enterica serovar
Typhimurium. Studies from Africa have suggested that this susceptibility is
related in part to the development of a high level of lipopolysaccharide (LPS)
specific IgG that is able to inhibit the killing of S. Typhimurium by
bactericidal antibodies in healthy individuals. To explore this issue further, we
examined the bactericidal activity against S. Typhimurium using serum and plasma
samples from healthy controls and various clinical subgroups of HIV-infected
adults in the United States. We found that the bactericidal activity in the
samples from HIV-positive elite controllers was comparable to that from healthy
individuals, whereas it was significantly reduced in HIV-positive viremic
controllers and untreated chronic progressors. As demonstrated previously for
healthy controls, the bactericidal activity of the plasma from the elite
controllers was inhibited by preincubation with S. Typhimurium LPS, suggesting
that it was mediated by anti-LPS antibodies. S. Typhimurium LPS-specific IgG was
significantly reduced in all subgroups of HIV-infected individuals.
Interestingly, and in contrast to the healthy controls, plasma from all HIV
positive subgroups inhibited in vitro killing of S. Typhimurium by plasma from a
healthy individual. Our results, together with the findings from Africa, suggest
that multiple mechanisms may be involved in the HIV-induced dysregulation of
humoral immunity to S. Typhimurium.
PMID- 25121778
TI - Decorin binding proteins A and B in the serodiagnosis of Lyme disease in North
America.
AB - The laboratory diagnosis of Lyme disease is based upon the detection of
antibodies generated against Borrelia burgdorferi using a two-tier assay,
typically consisting of an enzyme-linked immunosorbent assay (ELISA), followed by
a Western blot. This system, put into place to address the nonspecificity
associated with standalone first-tier assays, is insensitive for diagnosing early
infection, when most people seek care. The use of bacterial lysates or whole
protein antigens as first-tier assay targets contributes to nonspecificity due,
in part, to the presence of cross-reactive epitopes that are also found in other
bacteria. This precludes their use as sensitive standalone assays. The use of
peptides containing linear epitopes that are highly specific for B. burgdorferi
offers a method for reducing this cross-reactivity. In the present study, we
mapped the linear epitopes of the prominently expressed Borrelia adhesins decorin
binding protein A (DbpA) and DbpB. We identified several epitopes in each protein
that were highly conserved among North American strains of B. burgdorferi, and we
screened peptides containing specific epitopes using serum panels from early and
late Lyme disease patients. The individual peptides primarily detected IgM but
not IgG, while the proteins efficiently detected both IgM and IgG. While no
individual peptide demonstrated better utility for antibody detection than its
respective whole protein, an assay containing a combination of a DbpA and a DbpB
peptide adequately detected both IgM and IgG, accurately identifying 87.5%
(84/96) of the early Lyme disease patients and 80.0% (16/20) of the late Lyme
disease patients.
PMID- 25121776
TI - Analysis of mutant SOD1 electrophoretic mobility by Blue Native gel
electrophoresis; evidence for soluble multimeric assemblies.
AB - Mutations in superoxide dismutase 1 (SOD1) cause familial forms of amyotrophic
lateral sclerosis (fALS). Disease causing mutations have diverse consequences on
the activity and half-life of the protein, ranging from complete inactivity and
short half-life to full activity and long-half-life. Uniformly, disease causing
mutations induce the protein to misfold and aggregate and such aggregation
tendencies are readily visualized by over-expression of the proteins in cultured
cells. In the present study we have investigated the potential of using
immunoblotting of proteins separated by Blue-Native gel electrophoresis (BNGE) as
a means to identify soluble multimeric forms of mutant protein. We find that over
expressed wild-type human SOD1 (hSOD1) is generally not prone to form soluble
high molecular weight entities that can be separated by BNGE. For ALS mutant
SOD1, we observe that for all mutants examined (A4V, G37R, G85R, G93A, and
L126Z), immunoblots of BN-gels separating protein solubilized by digitonin
demonstrated varied amounts of high molecular weight immunoreactive entities.
These entities lacked reactivity to ubiquitin and were partially dissociated by
reducing agents. With the exception of the G93A mutant, these entities were not
reactive to the C4F6 conformational antibody. Collectively, these data
demonstrate that BNGE can be used to assess the formation of soluble multimeric
assemblies of mutant SOD1.
PMID- 25121779
TI - The Staurotypus turtles and aves share the same origin of sex chromosomes but
evolved different types of heterogametic sex determination.
AB - Reptiles have a wide diversity of sex-determining mechanisms and types of sex
chromosomes. Turtles exhibit temperature-dependent sex determination and
genotypic sex determination, with male heterogametic (XX/XY) and female
heterogametic (ZZ/ZW) sex chromosomes. Identification of sex chromosomes in many
turtle species and their comparative genomic analysis are of great significance
to understand the evolutionary processes of sex determination and sex chromosome
differentiation in Testudines. The Mexican giant musk turtle (Staurotypus
triporcatus, Kinosternidae, Testudines) and the giant musk turtle (Staurotypus
salvinii) have heteromorphic XY sex chromosomes with a low degree of
morphological differentiation; however, their origin and linkage group are still
unknown. Cross-species chromosome painting with chromosome-specific DNA from
Chinese soft-shelled turtle (Pelodiscus sinensis) revealed that the X and Y
chromosomes of S. triporcatus have homology with P. sinensis chromosome 6, which
corresponds to the chicken Z chromosome. We cloned cDNA fragments of S.
triporcatus homologs of 16 chicken Z-linked genes and mapped them to S.
triporcatus and S. salvinii chromosomes using fluorescence in situ hybridization.
Sixteen genes were localized to the X and Y long arms in the same order in both
species. The orders were also almost the same as those of the ostrich (Struthio
camelus) Z chromosome, which retains the primitive state of the avian ancestral Z
chromosome. These results strongly suggest that the X and Y chromosomes of
Staurotypus turtles are at a very early stage of sex chromosome differentiation,
and that these chromosomes and the avian ZW chromosomes share the same origin.
Nonetheless, the turtles and birds acquired different systems of heterogametic
sex determination during their evolution.
PMID- 25121782
TI - Abdominoplasty-derived dermal-fat graft augmentation gluteoplasty.
AB - BACKGROUND: Plastic surgeons are exploring novel techniques for augmentation
gluteoplasty as the demand for this procedure increases annually in the United
States. OBJECTIVES: The authors retrospectively reviewed a series of lower
abdominal dermal-fat graft augmentation gluteoplasties to validate the procedure.
METHODS: Nine consecutive patients underwent abdominoplasty or torsoplasty in
which 2 oval dermal-fat grafts were excised, de-epithelialized, and then
implanted into subfascial gluteal pockets for augmentation. All operations were
independently conducted by 1 of 2 surgeons at facilities in Maryland and New
Jersey. RESULTS: The mean age of the 9 female patients was 46 years. The mean
dermal-graft size was 188 cm(2), and the mean graft weight was 288 g. One graft
became infected and required excision 39 days after the procedure. There were no
other complications. All surviving grafts provided a substantial increase in
posterior projection and long-lasting gluteal volume. CONCLUSIONS: Dermal-fat
graft augmentation gluteoplasty provides a voluminous, natural-feeling, and
durable aesthetic result. The procedure should be considered a viable option for
patients undergoing abdominoplasty or torsoplasty, especially as more experience
is gained. LEVEL OF EVIDENCE: 4.
PMID- 25121780
TI - Structural characterization of the DC-SIGN-Lewis(X) complex.
AB - Dendritic cell-specific intracellular adhesion molecule-3-grabbing nonintegrin
(DC-SIGN) is a C-type lectin highly expressed on the surface of antigen
presenting dendritic cells. DC-SIGN mediates interactions among dendritic cells,
pathogens, and a variety of epithelia, myeloid cells, and endothelia by binding
to high mannose residues on pathogenic invaders or fucosylated residues on the
membranes of other immune cells. Although these interactions are normally
beneficial, they can also contribute to disease. The structural characterization
of binding geometries is therefore of interest as a basis for the construction of
mimetics that can mediate the effects of abnormal immune response. Here, we
report the structural characteristics of the interaction of the DC-SIGN
carbohydrate recognition domain (CRD) with a common fucosylated entity, the
Lewis(X) trisaccharide (Le(X)), using NMR methods. Titration of the monomeric DC
SIGN CRD with Le(X) monitored by 2D NMR revealed significant perturbations of DC
SIGN cross-peak positions in (1)H-(15)N heteronuclear single quantum coherence
(HSQC) spectra and identified residues near the binding site. Additionally,
saturation transfer difference (STD) and transferred nuclear Overhauser effect
(trNOE) NMR experiments, using a tetrameric form of DC-SIGN, identified binding
epitopes and bound conformations of the Le(X) ligand. The restraints derived from
these multiple experiments were used to generate models for the binding of Le(X)
to the DC-SIGN CRD. Ranking of the models based on the fit of model-based
simulations of the trNOE data and STD buildup curves suggested conformations
distinct from those seen in previous crystal structures. The new conformations
offer insight into how differences between binding of Lewis(X) and mannose
terminated saccharides may be propagated.
PMID- 25121784
TI - Effectiveness of prophylactic antibiotics in outpatient plastic surgery.
AB - BACKGROUND: The effectiveness of prophylactic antibiotics has not been
established for patients who undergo plastic surgery as outpatients, and
consensus guidelines for antibiotic administration in clean-contaminated plastic
surgery are not available. OBJECTIVES: In a retrospective study of outpatients,
the authors examined preoperative timing of prophylactic antibiotics, whether
postoperative antibiotics were administered, and whether any correlations existed
between these practices and surgical complications. METHODS: The medical records
of 468 plastic surgery outpatients were reviewed. Collected data included
preoperative antibiotic timing, postoperative antibiotic use, comorbidities, and
complications. Rates of complications were calculated and compared with other
data. RESULTS: All 468 patients received antibiotics preoperatively, but only 93
(19.9%) received them >=1 hour before the initial incision. Antibiotics were
administered 15 to 44 minutes before surgery in 217 patients (46.4%). There was
no significant difference in complication rates between the 315 patients who
received postoperative prophylactic antibiotics (16.2%) and the 153 who did not
(20.9%). Comorbidities had no bearing on postoperative complications.
CONCLUSIONS: Postoperative antibiotic prophylaxis may be unnecessary for
outpatient plastic surgery patients. LEVEL OF EVIDENCE: 3.
PMID- 25121786
TI - Anatomy of the sternal origin of the pectoralis major: implications for
subpectoral augmentation.
AB - BACKGROUND: The pectoralis major typically is manipulated for implant coverage
and pocket design in subpectoral breast augmentation. An understanding of its
anatomy can guide successful creation of the implant pocket. OBJECTIVES: The
authors evaluated the anatomy of the sternal origin of the pectoralis major to
inform surgical planning, help establish a technique for subpectoral augmentation
mammaplasty, and identify the most common locations of perforators. METHODS: The
sternal origins of 24 pectoralis major muscles were dissected and examined in 15
female cadavers to determine the structure and width of the pectoralis major
sternal origin and its relationship to the locations of internal mammary
perforators. RESULTS: The average width of the sternal origin of the pectoralis
major was 7.1 mm (range, 3 mm-1.8 cm). This width decreased slightly from the
second rib to the second intercostal space and then increased progressively in
the caudal direction toward the fifth rib. The sternal origin terminated an
average of 5.4 mm (range, 1-16 mm) from the midline, with the greatest distance
at the fifth rib and large variability throughout. A row of perforators from the
internal mammary artery traversed the subpectoral space an average of 2.7 cm from
the midline (range, 1-3.7 cm). CONCLUSIONS: The sternal origin of the pectoralis
major was thin and highly variable, suggesting that its partial release for
implant medialization during subpectoral augmentation is unsafe.
PMID- 25121785
TI - Will 1-stage implant salvage after periprosthetic breast infection ever be
routine? A 6-year successful experience.
AB - BACKGROUND: Concomitant with the recent increase in breast augmentations has been
an increase in periprosthetic infections necessitating further surgery. The
conventional treatment of periprosthetic infections has been a multistage
procedure involving explantation, control of infection, and reimplantation.
OBJECTIVES: The authors describe a 1-stage salvage procedure for the management
of periprosthetic infections. This technique may become the standard for managing
infection following cosmetic breast surgery. METHODS: The authors performed a
retrospective review of all patients who had periprosthetic infection following
cosmetic breast augmentation. The treatment included explantation, sequential
cleaning of the wound, and immediate insertion of a new prosthesis and drain. All
patients received intravenous antibiotics postoperatively. Of 3012 patients
undergoing primary breast augmentation, periprosthetic infection developed in 17
patients. These 17 patients underwent 1-stage implant salvage. Patients were
monitored for <=6 years. RESULTS: All implants were retained; aesthetic results
were satisfactory; and no significant adverse events were recorded after implant
salvage. CONCLUSIONS: One-stage implant salvage for periprosthetic infection has
similar outcomes to conventional multistage procedures and may be preferred by
patients. LEVEL OF EVIDENCE: 4.
PMID- 25121787
TI - The oncoplastic reduction approach to breast conservation therapy: benefits for
margin control.
AB - BACKGROUND: Reduction mammaplasty during lumpectomy allows more generous
resection and minimizes potential for poor cosmesis as compared with breast
conservation therapy alone. OBJECTIVES: The authors assessed the benefits of
oncoplastic reduction for margin status in patients with breast cancer by
conducting a retrospective review of cases of tumor resection alone vs tumor
resection with oncoplastic reduction. METHODS: Patients with breast cancer who
underwent lumpectomy performed by a single oncologic surgeon between 2009 and
2013 were included. Patients were stratified into 2 groups based on surgical
procedure: tumor resection with oncoplastic reduction (group 1) vs tumor
resection alone (group 2). Patient demographics including risk factors,
diagnosis, cancer stage, and procedure type were recorded. Tumor size, specimen
weight, width of narrowest margin, and receptor status were determined. Outcome
variables included margin positivity (<=1 mm), need for re-excision, and
conversion to completion mastectomy. RESULTS: A total of 222 breasts from 207
patients were included in the study: 83 in group 1 and 139 in group 2. The
patients in group 1 had a lower incidence of positive margins and wider free
surgical margins, required re-excision less often, and went on to completion
mastectomy less often. Patients in group 1 were younger and had cancer that was
more advanced. When controlling for these variables on multivariate regression
analysis, the oncoplastic technique was independently associated with fewer
positive margins and fewer instances of re-excision. CONCLUSIONS: The oncoplastic
reduction technique achieves wider free margins and less often necessitates re
excision or subsequent mastectomy. The long-term oncologic effect of this
approach deserves further study. LEVEL OF EVIDENCE: 4.
PMID- 25121788
TI - The pull-up spreader high (PUSH) technique for nasal tip support.
AB - BACKGROUND: Nasal tip depression is associated with nasal valve collapse. The
pull-up spreader high (PUSH) technique was developed to enlarge the nasal dorsum
and upwardly rotate and define the nasal tip by lifting the domes. OBJECTIVES:
The authors reviewed a case series to assess the long-term effectiveness of the
PUSH technique in improving nasal airflow and aesthetic outcomes. METHODS: This
retrospective study included 50 consecutive cases of PUSH rhinoplasty. Objective
(acoustic rhinomanometry) and subjective (patient questionnaire) evaluations of
the stability of the aesthetic result and improvement of airflow were conducted
before and 3 years after PUSH rhinoplasty. RESULTS: PUSH rhinoplasty resulted in
long-term stability of the aesthetic effect. All patients had pleasing aesthetic
results and a general improvement in the nasal airway. When the degree of nasal
obstruction was scored from 1 (greatest obstruction) to 10 (least obstruction),
22 patients rated their nasal function improved to a score of 10 and 28 patients
to a score of 8. Rhinomanometry indicated that only 1 patient had worsened nasal
airflow. CONCLUSIONS: The PUSH technique enables stable upward rotation and
improved definition of the severely depressed nasal tip through an open approach.
LEVEL OF EVIDENCE: 4.
PMID- 25121789
TI - Task shifting for non-communicable disease management in low and middle income
countries--a systematic review.
AB - BACKGROUND: One potential solution to limited healthcare access in low and middle
income countries (LMIC) is task-shifting- the training of non-physician
healthcare workers (NPHWs) to perform tasks traditionally undertaken by
physicians. The aim of this paper is to conduct a systematic review of studies
involving task-shifting for the management of non-communicable disease (NCD) in
LMIC. METHODS: A search strategy with the following terms "task-shifting", "non
physician healthcare workers", "community healthcare worker", "hypertension",
"diabetes", "cardiovascular disease", "mental health", "depression", "chronic
obstructive pulmonary disease", "respiratory disease", "cancer" was conducted
using Medline via Pubmed and the Cochrane library. Two reviewers independently
reviewed the databases and extracted the data. FINDINGS: Our search generated
7176 articles of which 22 were included in the review. Seven studies were
randomised controlled trials and 15 were observational studies. Tasks performed
by NPHWs included screening for NCDs and providing primary health care. The
majority of studies showed improved health outcomes when compared with usual
healthcare, including reductions in blood pressure, increased uptake of
medications and lower depression scores. Factors such as training of NPHWs,
provision of algorithms and protocols for screening, treatment and drug titration
were the main enablers of the task-shifting intervention. The main barriers
identified were restrictions on prescribing medications and availability of
medicines. Only two studies described cost-effective analyses, both of which
demonstrated that task-shifting was cost-effective. CONCLUSIONS: Task-shifting
from physicians to NPHWs, if accompanied by health system re-structuring is a
potentially effective and affordable strategy for improving access to healthcare
for NCDs. Since the majority of study designs reviewed were of inadequate
quality, future research methods should include robust evaluations of such
strategies.
PMID- 25121791
TI - Flow-diverting stents for intracranial bifurcation aneurysm treatment.
AB - BACKGROUND: Although initially considered safe when covering bifurcation sites,
flow-diverting stents may provoke thrombosis of side branches that are covered
during aneurysm treatment. OBJECTIVE: To understand the occurrence and clinical
expression of side-branch remodeling in distal intracranial arterial sites after
flow diverter deployment by means of correlation of imaging and clinical data.
METHODS: We analyzed our prospectively collected data on a series of patients
treated with flow diverters for intracranial aneurysms at bifurcation sites. From
February 2011 to May 2013, 32 patients with 37 aneurysms (anterior communicating
artery, 9 [24.3%]; anterior cerebral artery, 5 [13.5%]; middle cerebral artery,
19 (51.4%); terminal internal carotid artery, 4 [10.8%]) were treated. We divided
aneurysms into 2 groups based on the side branches covered by the stent during
treatment. Group A consisted of cases with side branches that supplied brain
territories also receiving a direct collateral supply. Group B consisted of cases
in which side branches supplied territories without direct collateral supply. The
2 groups were compared statistically. RESULTS: Total exclusion occurred in 97.3%
of aneurysms at follow-up. Initial modified Rankin Scale (mRS) score was 0 to 1
for 29 patients (90.6%) and 2 for 3 patients (9.4%). New permanent neurological
deficit was reported in 3 patients (9.4%). At the 6-month follow-up, the mRS
score was 0 to 1 for 31 patients (96.8%) and 3 for 1 patient (3.2%). Although
78.5% of side branches in group A underwent narrowing or occlusion after 6
months, no new stroke was found on magnetic resonance imaging. CONCLUSION:
Symptomatic modifications of side branches after flow diverter treatment depend
on the extent and type of collateral supply.
PMID- 25121792
TI - A novel protocol of continuous navigation guidance for endoscopic third
ventriculostomy.
AB - BACKGROUND: Although considered a standard neurosurgical procedure, endoscopic
third ventriculostomy (ETV) is associated with a relatively high complication
rate that is predominantly related to malpositioning of the trajectory.
OBJECTIVE: To develop an advanced navigation protocol for ETV, assess its
possible benefits over commonly used ETV trajectories, and apply this protocol
during surgery. METHODS: After development of our advanced protocol, the imaging
data of 59 patients who underwent ETV without navigation guidance was transferred
to our navigation software. An individualized endoscope trajectory was created
according to our protocol in all cases. This trajectory was compared with 2
standard trajectories, especially with regard to the distance to relevant
neuronal structures: a trajectory manually measured on preoperative radiological
images, as performed in all 59 cases, and a trajectory resulting from a commonly
used fixed coronal burr hole. Subsequently, we applied the protocol in 15 ETVs to
assess the feasibility and procedural complications. RESULTS: Our individualized
trajectory resulted in a significantly greater distance to the margins of the
foramen of Monro, and the burr hole was located more posteriorly from the coronal
suture in comparison with the standard trajectories. The advanced ETV technique
was feasible in all 15 procedures, and no major complications occurred in any
procedure. In 1 patient, a fornix contusion without clinical correlation was
observed. CONCLUSION: Our data indicate that the proposed navigation protocol for
ETV optimizes the distance of the endoscope to important neuronal structures.
Continuous endoscope and puncture device guidance may further add to the safety
of this procedure.
PMID- 25121793
TI - Early postmarket experience after US Food and Drug Administration approval with
the Trevo device for thrombectomy for acute ischemic stroke.
AB - BACKGROUND: TREVO 2 showed the Trevo stent retriever to be more successful for
revascularization than Merci for acute stroke intervention in patients treated
within 8 hours of symptom onset. These results led to US Food and Drug
Administration approval of Trevo. OBJECTIVE: To report the first postmarket
experience with Trevo since US Food and Drug Administration approval at a single
high-volume comprehensive stroke center in the United States. METHODS: A
retrospective analysis of prospectively collected data was conducted in patients
who underwent intervention for ischemic stroke with the Trevo device. Trevo was
used alone or in conjunction with other intra-arterial devices. Two groups of
patients were identified: those with symptom onset within (group 1) and those
with symptom onset beyond (group 2) 8 hours. Recanalization, outcome, symptomatic
intracranial hemorrhage, and in-hospital and 90-day mortality were assessed.
RESULTS: Fifty-two patients were identified, 27 in group 1 and 25 in group 2.
Thrombolysis in Cerebral Infarction grade 2 to 3 revascularization was achieved
in 93% of group 1 and 84% of group 2 patients. In-hospital mortality and
symptomatic intracranial hemorrhage rates were 3.8% and 12% for groups 1 and 2,
respectively. Ninety-day mortality was 15% and 24% for groups 1 and 2,
respectively. In groups 1 and 2, 48% and 42% of patients, respectively, had good
outcomes (modified Rankin Scale score, 0-2), and 50% in both groups of patients
achieved Thrombolysis in Cerebral Infarction grade 3 revascularization. Group 2
had longer revascularization times and required adjuvant devices more frequently.
CONCLUSION: Our postmarket experience shows that in highly selected patients
Trevo is safe and effective, even beyond 8 hours, despite longer procedure times
and the need for adjuvant devices.
PMID- 25121794
TI - Journal club: the impact of body mass index on hospital stay and complications
after spinal fusion.
PMID- 25121795
TI - Response to journal club: the impact of body mass index on hospital stay and
complications after spinal fusion.
PMID- 25121790
TI - Role of hemoglobin and iron in hydrocephalus after neonatal intraventricular
hemorrhage.
AB - BACKGROUND: Neonatal germinal matrix hemorrhage/intraventricular hemorrhage is
common and often results in hydrocephalus. The pathogenesis of posthemorrhagic
hydrocephalus is not fully understood. OBJECTIVE: To explore the potential role
of hemoglobin and iron released after hemorrhage. METHODS: Artificial
cerebrospinal fluid (aCSF), hemoglobin, or iron was injected into the right
lateral ventricle of postnatal day-7 Sprague Dawley rats. Ventricle size, heme
oxygenase-1 (HO-1) expression, and the presence of iron were evaluated 24 and 72
hours after injection. A subset of animals was treated with an iron chelator
(deferoxamine) or vehicle for 24 hours after hemoglobin injection, and ventricle
size and cell death were evaluated. RESULTS: Intraventricular injection of
hemoglobin and iron resulted in ventricular enlargement at 24 hours compared with
the injection of aCSF. Protoporphyrin IX, the iron-deficient immediate heme
precursor, did not result in ventricular enlargement after injection into the
ventricle. HO-1, the enzyme that releases iron from heme, was increased in the
hippocampus and cortex of hemoglobin-injected animals at 24 hours compared with
aCSF-injected controls. Treatment with an iron chelator, deferoxamine, decreased
hemoglobin-induced ventricular enlargement and cell death. CONCLUSION:
Intraventricular injection of hemoglobin and iron can induce hydrocephalus.
Treatment with an iron chelator reduced hemoglobin-induced ventricular
enlargement. This has implications for the pathogenesis and treatment of
posthemorrhagic hydrocephalus. ABBREVIATIONS: aCSF, artificial cerebrospinal
fluidDAB, 3,3'-diaminobenzidine-4HClGMH-IVH, germinal matrix
hemorrhage/intraventricular hemorrhageHO-1, heme oxygenase-1ICH, intracerebral
hemorrhagePBS, phosphate-buffered salineSVZ, subventricular zoneTBST, tris
buffered saline with Tween 20.
PMID- 25121796
TI - Let's study how worker health affects the psychosocial work environment.
PMID- 25121799
TI - Disability days, United States, 1971.
AB - Data are presented in this report on the total number and annual rates per person
for disability days experienced by the civilian, noninstitutionalized population
for 1971. Disability days included are restricted-activity days, bed days, work
loss days, and school-loss days. A day of restricted activity is defined as a day
on which a person reduced his normal activities for the entire day because of
illness or injury. Bed days, work-loss days, and school-loss days are included in
the total number of restricted-activity days. Demographic characteristics used to
described the persons with disability days are age, sex, place of residence,
geographic region, famiIy income, usual activity, color, employment status, and
for the currently employed population, industry and occupation. Previous reports
of data from the Health Interview Survey on disability days are pubIished for
July 1961-June 1962, July 1963-June 1964, July 1965-June 1966, and January
December 1968 in Vital and Health Statistics, Series 10, Numbers 4, 24, 47, and
67. Data on work-loss days for the currently employed during 1968 are discussed
in Series 10, Number 71. Summary data from July 1965-June 1966 and January
December 1968 are also shown in this report for comparative purposes.
PMID- 25121798
TI - Rethinking unmet need: Determinants of contraceptive use in Santiago, the
Dominican Republic.
AB - Inadequate access to contraceptives is often considered the primary source of
unmet need among women who desire to prevent pregnancy. This study evaluates two
potential determinants of contraceptive use among Dominican women: (1) perceived
access to family planning and (2) perceived personal reproductive control, a
measure based in psychological theories of locus of control. Sexually active
women aged 18-45 who did not desire fertility were surveyed to assess influences
on contraceptive use. In-depth interviews were conducted among a subset of
participants to contextualise survey results. Fewer than half (49%) of the 80
survey respondents had used contraception in the last 3 months. Higher personal
reproductive control was significantly related to contraceptive use (aOR 1.18,
95% CI 1.04-1.34), however, higher perceived access to contraceptives was not
(aOR 1.09, 95% CI 0.97-1.23). Male partner influence was identified as a barrier
to contraceptive use. In this population, high personal reproductive control is a
better predictor of contraceptive use than perceived access.
PMID- 25121800
TI - [Christoph Scheiner and the physiological optics of the eye].
PMID- 25121801
TI - [Treatment options for nystagmus].
AB - The goal of treatment for nystagmus is to reduce or to abolish the typical
symptoms associated with nystagmus. These are (i) reduction of visual acuity (and
amblyopia in infantile nystagmus), (ii) abnormal head posture (with possible
secondary changes of cervical spine) and (iii) oscillopsia (often connected with
vertigo and disorders of gait and orientation). Treatment strategies include
pharmacological treatment, surgical therapy and optical devices. Choice of
treatment depends on the type of nystagmus and its characteristics. SURGICAL
THERAPY: The following surgical procedures were successfully used as treatment of
selected symptoms: (i) unilateral recess-resect surgery of the dominant eye in
infantile esotropia with latent nystagmus for the relief of abnormal head
posture, (ii) Kestenbaum operation of both eyes in infantile nystagmus syndrome
with excentric null zone and abnormal head posture, (iii) recess-resect surgery
to produce artificial exophoria in infantile nystagmus syndrome. PHARMACOLOGICAL
TREATMENT: Depending on the pathophysiology of different types of nystagmus,
several drugs were effective in clinical application (off-label use): (i)
gabapentin (non-selective GABAergic and anti-glutamatergic effect): up to 2400
mg/d in infantile nystagmus, acquired pendular nystagmus and oculopalatal tremor,
(ii) nemantine (anti-glutamatergic effect): dosage up to 40 mg/d in infantile
nystagmus, also in acquired pendular nystagmus and oculopalatal tremor, (iii)
baclofen (GABA-B-receptor agonist): 3 * 5-10 mg/d in periodic alternating
nystagmus and in upbeat nystagmus, (iv) 4-aminopyridine (non-selective blocker of
voltage-gated potassium channels): 3 * 5 mg/d or 1-2 * 10 mg Fampridin in
downbeat nystagmus and upbeat nystagmus, (v) acetazolamide (carbonic anhydrase
inhibitor): in hereditary episodic ataxia type 2. OPTICAL DEVICES: (i) Contact
lenses are used in infantile nystagmus in order to overcome negative effects of
eye glasses in abnormal head posture, lateral gaze, and higher refractive errors,
(ii) spectacle prisms are useful to induce an artificial exophoria (base-out
prisms) or to shift an excentric null zone (base in direction of head posture) of
infantile nystagmus with abnormal head posture, (iii) low vision aids may be
necessary and should be prescribed according to magnification requirements.
PMID- 25121803
TI - An approach toward constructing the trioxadispiroketal core in the DEF-ring of
(+)-spirastrellolide A.
AB - A concise and stereoselective synthesis of the trioxadispiroketal motif that
embodies the DEF-ring of the marine macrolide (+)-spirastrellolide A is
described. The synthetic approach features a sequence of cyclic acetal tethered
ring-closing metathesis and Suarez oxidative cyclization, thereby constituting a
viable strategy for constructing the Northern Half.
PMID- 25121802
TI - Characteristics of fishing operations, environment and life history contributing
to small cetacean bycatch in the northeast Atlantic.
AB - Fisheries bycatch is a key threat to cetacean species globally. Managing the
impact requires an understanding of the conditions under which animals are caught
and the sections of the population affected. We used observer data collected on
an albacore tuna gillnet fishery in the northeast Atlantic, to assess operational
and environmental factors contributing to bycatch of common and striped dolphins,
using generalised linear models and model averaging. Life history demographics of
the captured animals were also investigated. In both species, young males
dominated the catch. The age ratio of common dolphins was significantly different
from that estimated for the population in the region, based on life tables (G =
17.1, d.f. = 2, p = 0.002). Skewed age and sex ratios may reflect varying
vulnerability to capture, through differences in behaviour or segregation in
populations. Adult females constituted the second largest portion of the bycatch
for both species, with potential consequences for population sustainability.
Depth was the most important parameter influencing bycatch of both species and
reflected what is known about common and striped dolphin habitat use in the
region as the probability of catching common dolphins decreased, and striped
dolphins increased, with increasing depth. Striped dolphin capture was similarly
influenced by the extent to which operations were conducted in daylight, with the
probability of capture increasing with increased operations in the pre-sunset and
post-sunrise period, potentially driven by increased ability of observers to
record animals during daylight operations, or by diurnal movements increasing
contact with the fishery. Effort, based on net length and soak time, had little
influence on the probability of capturing either species. Our results illustrate
the importance of assessing the demographic of the animals captured during
observer programmes and, perhaps more importantly, suggest that effort
restrictions alone may not be sufficient to eradicate bycatch in areas where
driftnets and small cetaceans co-occur.
PMID- 25121805
TI - Flowing gas in mass spectrometer: method for characterization and impact on ion
processing.
AB - Mass spectrometers are complex instrumentation systems where ions are transferred
though different pressure regions and mass-analyzed under high vacuum. In this
work, we have investigated the impact of the gas flows that exit almost
universally in all pressure regions. We developed a method that incorporates the
dynamic gas field with the electric field in the simulation of ion trajectories.
The scope of the electro-hydrodynamic simulation (EHS) method was demonstrated
for characterizing the ion optical systems at atmospheric pressure interfaces.
With experimental validation, the trapping of the externally injected ions in a
linear ion trap at low pressure was also studied. Further development of the EHS
method and the knowledge acquired in this research are expected to be useful in
the design of hybrid instruments and the study of ion energetics.
PMID- 25121804
TI - A randomized, double-blind, placebo-controlled 12 week trial of acetaminophen
extended release for the treatment of signs and symptoms of osteoarthritis.
AB - OBJECTIVE: Determine efficacy and safety of acetaminophen extended release (ER)
1300 mg given three times daily compared to placebo for relieving signs and
symptoms of hip or knee osteoarthritis. RESEARCH DESIGN AND METHODS: Sixty
investigators at 58 private, ambulatory, primary care sites in the US enrolled
542 outpatient adults >=40 years old with moderate to severe idiopathic
osteoarthritis pain into a randomized, placebo-controlled, double-blind 12 week
clinical trial. Patients were randomly assigned to treatment given three times
daily of acetaminophen 1300 mg (n = 267) or placebo (n = 275). RESULTS: The three
primary endpoints measured through week 12 favored acetaminophen ER as follows:
least squares (LS) mean change from baseline for WOMAC physical function subscale
score was significantly greater for acetaminophen ER than for placebo (P =
0.011); LS mean patient's global assessment of response to therapy was
significantly greater for acetaminophen ER than for placebo (P = 0.010); and LS
mean change from baseline for WOMAC pain subscale score was marginally greater
for acetaminophen ER than for placebo (P = 0.054). LS mean change from baseline
for secondary endpoints through week 12 also favored acetaminophen ER compared
with placebo: significantly for WOMAC stiffness subscale score (P = 0.004),
significantly for WOMAC total index score (P = 0.013), and marginally for
Nottingham Health Profile energy subscale score (P = 0.057). The percentage of
patients with any adverse event was similar for both treatment groups. Hepatic
transaminases exceeded 3 * ULN in seven acetaminophen ER patients and one placebo
patient. Elevations were attributed to health conditions in three of seven
acetaminophen ER patients; elevations in the remaining four patients returned to
or toward normal. CONCLUSIONS: Acetaminophen ER 1300 mg, a nonprescription drug,
given three times daily, can provide effective relief of signs and symptoms of
osteoarthritis of the hip or knee and was well tolerated. ClinicalTrials.gov
registration number: NCT00240799.
PMID- 25121806
TI - Iran plans to ban vasectomies and female sterilisation to boost population.
PMID- 25121807
TI - Disease progression in Plasmodium knowlesi malaria is linked to variation in
invasion gene family members.
AB - Emerging pathogens undermine initiatives to control the global health impact of
infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a
malaria parasite of Southeast Asian macaques, has entered the human population.
P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human
infections, and the World Health Organization guidelines for severe malaria list
hyperparasitaemia among the measures of severe malaria in both infections. Not
all patients with P. knowlesi infections develop hyperparasitaemia, and it is
important to determine why. Between isolate variability in erythrocyte invasion,
efficiency seems key. Here we investigate the idea that particular alleles of two
P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein
Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression.
Pknbpxa and Pknbpxb reference DNA sequences were generated from five
geographically and temporally distinct P. knowlesi patient isolates. Polymorphic
regions of each gene (approximately 800 bp) were identified by haplotyping 147
patient isolates at each locus. Parasitaemia in the study cohort was associated
with markers of disease severity including liver and renal dysfunction,
haemoglobin, platelets and lactate, (r = >= 0.34, p = <0.0001 for all). Seventy
five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134
(92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two
Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa
and Pknbpxb alleles within the groups had significantly higher parasitaemia and
other markers of disease severity. Our study strongly suggests that P. knowlesi
invasion gene variants contribute to parasite virulence. We focused on two
invasion genes, and we anticipate that additional virulent loci will be
identified in pathogen genome-wide studies. The multiple sustained entries of
this diverse pathogen into the human population must give cause for concern to
malaria elimination strategists in the Southeast Asian region.
PMID- 25121808
TI - Transnational, social, and neighborhood ties and smoking among Latino immigrants:
does gender matter?
AB - OBJECTIVES: We examined whether transnational ties, social ties, and neighborhood
ties were independently associated with current smoking status among Latino
immigrants. We also tested interactions to determine whether these associations
were moderated by gender. METHODS: We conducted a series of weighted logistic
regression analyses (i.e., economic remittances, number of return visits, friend
support, family support, and neighborhood cohesion) using the Latino immigrant
subsample (n = 1629) of the National Latino and Asian American Study in 2002 and
2003. RESULTS: The number of past-year return visits to the country-of-origin was
positively associated with current smoker status. Gender moderated the
association between economic remittances, friend support, and smoking. Remittance
behavior had a protective association with smoking, and this association was
particularly pronounced for Latino immigrant women. Friendship support lowered
the odds of smoking among men, but not women. CONCLUSIONS: Our results underscore
the growing importance of transnational networks for understanding Latino
immigrant health and the gendered patterns of the associations between social
ties, transnational ties, and health risk behaviors.
PMID- 25121809
TI - Science as an early driver of policy: child labor reform in the early Progressive
Era, 1870-1900.
AB - Scientific evidence is an increasingly important driver of social and
environmental policy concerning child health. This trend began earlier than
generally recognized. The child labor reform movement of the Gilded Age and early
Progressive Era reflected not only moral and economic forces but also the
dramatic advances during the later decades of the 19th century in scientific
knowledge concerning children's biological and psychological vulnerability to
environmental and psychosocial stressors. The growing importance of scientific
information in shaping policy concerning children's health between 1870 and 1900
is illustrated by the events leading up to and following the New York State Child
Labor Law of 1886. Child labor reform during this period was a critical step in
the development of a science-based as well as a value-driven movement to protect
children's environmental health and well-being that continues today.
PMID- 25121811
TI - Instituting a sugar-sweetened beverage ban: experience from a children's
hospital.
AB - Sugar-sweetened beverage (SSB) consumption is linked to increased weight and
obesity in children and remains the major source of added sugar in the typical US
diet across all age groups. In an effort to improve the nutritional offerings for
patients and employees within our institution, Nationwide Children's Hospital in
Columbus, Ohio, implemented an SSB ban in 2011 in all food establishments within
the hospital. In this report, we describe how the ban was implemented. We found
that an institutional SSB ban altered beverage sales without revenue loss at
nonvending food locations. From a process perspective, we found that successful
implementation requires excellent communication and bold leadership at several
levels throughout the hospital environment.
PMID- 25121810
TI - A framework for evaluating the impact of obesity prevention strategies on
socioeconomic inequalities in weight.
AB - We developed a theoretical framework to organize obesity prevention interventions
by their likely impact on the socioeconomic gradient of weight. The degree to
which an intervention involves individual agency versus structural change
influences socioeconomic inequalities in weight. Agentic interventions, such as
standalone social marketing, increase socioeconomic inequalities. Structural
interventions, such as food procurement policies and restrictions on unhealthy
foods in schools, show equal or greater benefit for lower socioeconomic groups.
Many obesity prevention interventions belong to the agento-structural types of
interventions, and account for the environment in which health behaviors occur,
but they require a level of individual agency for behavioral change, including
workplace design to encourage exercise and fiscal regulation of unhealthy foods
or beverages. Obesity prevention interventions differ in their effectiveness
across socioeconomic groups. Limiting further increases in socioeconomic
inequalities in obesity requires implementation of structural interventions.
Further empirical evaluation, especially of agento-structural type interventions,
remains crucial.
PMID- 25121812
TI - Sexual orientation, adult connectedness, substance use, and mental health
outcomes among adolescents: findings from the 2009 New York City Youth Risk
Behavior Survey.
AB - OBJECTIVES: We examined associations between identifying as lesbian, gay, or
bisexual (LGB) and lacking a connection with an adult at school on adolescent
substance use and mental health outcomes including suicidality. METHODS: We
analyzed data from the 2009 New York City Youth Risk Behavior Survey (n=8910).
Outcomes of interest included alcohol use, marijuana use, illicit drug use,
depressive symptomatology, suicide ideation, and suicide attempt. RESULTS: The
prevalence of each outcome was significantly higher among LGB adolescents than
heterosexual adolescents and among those who lacked an adult connection at school
than among those who did have such a connection. Even when LGB adolescents had an
adult connection at school, their odds of most outcomes were significantly higher
than for heterosexual adolescents. Those LGB adolescents who lacked a school
adult connection had the poorest outcomes (about 45% reported suicide ideation;
31% suicide attempt). CONCLUSIONS: Adolescents who are LGB, particularly those
who lack a connection with school adults, are at high risk for substance use and
poorer mental health outcomes. Interventions should focus on boosting social
support and improving outcomes for this vulnerable group.
PMID- 25121813
TI - Physical dating violence victimization among sexual minority youth.
AB - OBJECTIVES: We examined (1) whether sexual minority youths (SMYs) are at
increased risk for physical dating violence victimization (PDVV) compared with
non-SMYs, (2) whether bisexual youths have greater risk of PDVV than lesbian or
gay youths, (3) whether youths who have had sexual contact with both sexes are
more susceptible to PDVV than youths with same sex-only sexual contact, and (4)
patterns of PDVV among SMYs across demographic groups. METHODS: Using 2 measures
of sexual orientation, sexual identity and sexual behavior, and compiling data
from 9 urban areas that administered the Youth Risk Behavior Surveys from 2001 to
2011, we conducted logistic regression analyses to calculate odds of PDVV among
SMYs across demographic sub-samples. RESULTS: SMYs have significantly increased
odds of PDVV compared with non-SMYs. Bisexual youths do not have significantly
higher odds of PDVV than gay or lesbian youths, but youths who had sexual contact
with both-sexes possess significantly higher odds of PDVV than youths with same
sex-only sexual contact. These patterns hold for most gender, grade, and
racial/ethnic subgroups. CONCLUSIONS: Overall, SMYs have greater odds of PDVV
versus non-SMYs. Among SMYs, youths who had sexual contact with both sexes have
greater odds of PDVV than youths with same sex-only sexual contact. Prevention
programs that consider sexual orientation, support tolerance, and teach coping
and conflict resolution skills could reduce PDVV among SMYs.
PMID- 25121814
TI - The Affordable Care Act and emergency care.
AB - The Affordable Care Act (ACA) will have far-reaching effects on the way health
care is designed and delivered. Several elements of the ACA will directly affect
both demand for ED care and expectations for its role in providing coordinated
care. Hospitals will need to employ strategies to reduce ED crowding as the ACA
expands insurance coverage. Discussions between EDs and primary care physicians
about their respective roles providing acute unscheduled care would promote the
goals of the ACA.
PMID- 25121815
TI - A statewide collaboration to initiate mental health screening and assess services
for detained youths in Indiana.
AB - OBJECTIVES: We describe a statewide effort to implement detention-based mental
health screening and assess follow-up services offered to detained youths in
Indiana. METHODS: A total of 25,265 detention stays (15,461 unique youths)
occurred between January 1, 2008, and December 31, 2011, across 16 detention
centers participating in the Indiana Juvenile Mental Health Screening Project. We
collected screening results and reports of detention-based follow-up mental
health services and referrals from justice system records. RESULTS: Approximately
21% of youths screened positive for mental health issues requiring follow-up. A
positive screen significantly predicted that youths would receive a follow-up
mental health service or referral while detained or upon detention center
discharge, compared with youths who did not screen positive (61% vs 39%).
Logistic regression models indicated that a positive screen was associated with
(1) contact with a mental health clinician within 24 hours of detention center
intake and (2) a mental health referral upon discharge. White youths were more
likely than minorities to receive both follow-up services. CONCLUSIONS: Future
statewide efforts to improve the mental health of detained youths should
incorporate standards for providing appropriate follow-up services in detention
centers.
PMID- 25121816
TI - The Montana Radon Study: social marketing via digital signage technology for
reaching families in the waiting room.
AB - OBJECTIVES: I tested a social marketing intervention delivered in health
department waiting rooms via digital signage technology for increasing radon
program participation among priority groups. METHODS: I conducted a tri-county,
community-based study over a 3-year period (2010-2013) in a high-radon state by
using a quasi-experimental design. We collected survey data for eligible
participants at the time of radon test kit purchase. RESULTS: Radon program
participation increased at the intervention site (t38 = 3.74; P = .001; 95%
confidence interval [CI] = 4.8, 16.0) with an increase in renters (chi(2)1,228 =
4.3; P = .039), Special Supplementary Nutrition Program for Women, Infants, and
Children families (chi(2)1,166 = 3.13; P = .077) and first-time testers
(chi(2)1,228 = 10.93; P = .001). Approximately one third (30.3%; n = 30)
attributed participation in the radon program to viewing the intervention
message. The intervention crossover was also successful with increased monthly
kit sales (t37 = 2.69; P = .01; 95% CI = 1.20, 8.47) and increased households
participating (t23 = 4.76; P < .001; 95% CI = 3.10, 7.88). CONCLUSIONS: A social
marketing message was an effective population-based intervention for increasing
radon program participation. The results prompted policy changes for Montana
radon programming and adoption of digital signage technology by 2 health
departments.
PMID- 25121818
TI - Using vignettes to tap into moral reasoning in public health policy: practical
advice and design principles from a study on food advertising to children.
AB - In this article, we describe a process for designing and applying vignettes in
public health policy research and practice. We developed this methodology for a
study on moral reasoning underpinning policy debate on food advertising to
children. Using vignettes prompted policy actors who were relatively entrenched
in particular ways of speaking professionally about a controversial and ethically
challenging issue to converse in a more authentic and reflective way. Vignettes
hold benefits and complexities. They can focus attention on moral conflicts, draw
out different types of evidence to support moral reasoning, and enable
simultaneous consideration of real and ideal worlds. We suggest a process and
recommendations on design features for crafting vignettes for public health
policy.
PMID- 25121817
TI - The relationship between gun ownership and stranger and nonstranger firearm
homicide rates in the United States, 1981-2010.
AB - OBJECTIVES: We examined the relationship between gun ownership and stranger
versus nonstranger homicide rates. METHODS: Using data from the Supplemental
Homicide Reports of the Federal Bureau of Investigation's Uniform Crime Reports
for all 50 states for 1981 to 2010, we modeled stranger and nonstranger homicide
rates as a function of state-level gun ownership, measured by a proxy,
controlling for potential confounders. We used a negative binomial regression
model with fixed effects for year, accounting for clustering of observations
among states by using generalized estimating equations. RESULTS: We found no
robust, statistically significant correlation between gun ownership and stranger
firearm homicide rates. However, we found a positive and significant association
between gun ownership and nonstranger firearm homicide rates. The incidence rate
ratio for nonstranger firearm homicide rate associated with gun ownership was
1.014 (95% confidence interval=1.009, 1.019). CONCLUSIONS: Our findings challenge
the argument that gun ownership deters violent crime, in particular, homicides.
PMID- 25121820
TI - Reducing tobacco use and access through strengthened minimum price laws.
AB - Higher prices reduce consumption and initiation of tobacco products. A minimum
price law that establishes a high statutory minimum price and prohibits the
industry's discounting tactics for tobacco products is a promising pricing
strategy as an alternative to excise tax increases. Although some states have
adopted minimum price laws on the basis of statutorily defined price "markups"
over the invoice price, existing state laws have been largely ineffective at
increasing the retail price. We analyzed 3 new variations of minimum price laws
that hold great potential for raising tobacco prices and reducing consumption:
(1) a flat rate minimum price law similar to a recent enactment in New York City,
(2) an enhanced markup law, and (3) a law that incorporates both elements.
PMID- 25121819
TI - The implications of fundamental cause theory for priority setting.
AB - Application of fundamental cause theory to Powers and Faden's model of social
justice highlights the ethical superiority of upstream public health
interventions. In this article, I assess the ramifications of fundamental cause
theory specifically in context of public health priority setting. Ethically
optimal public health policy simultaneously maximizes overall population health
and compresses health inequalities. The fundamental cause theory is an important
framework in helping to identify which categories of public health interventions
are most likely to advance these twin goals.
PMID- 25121821
TI - Sexual identity, partner gender, and sexual health among adolescent girls in the
United States.
AB - OBJECTIVES: We examined associations between adolescent girls' sexual identity
and the gender of their sexual partners, on one hand, and their reports of sexual
health behaviors and reproductive health outcomes, on the other. METHODS: We
analyzed weighted data from pooled Youth Risk Behavior Surveys (2005 and 2007)
representative of 13 US jurisdictions, focusing on sexually experienced girls in
8th through 12th grade (weighted n=6879.56). We used logistic regression with
hierarchical linear modeling to examine the strength of associations between
reports about sexual orientation and sexual and reproductive health. RESULTS:
Sexual minority girls consistently reported riskier behaviors than did other
girls. Lesbian girls' reports of risky sexual behaviors (e.g., sex under the
influence of drugs or alcohol) and negative reproductive health outcomes (e.g.,
pregnancy) were similar to those of bisexual girls. Partner gender and sexual
identity were similarly strong predictors of all of the sexual behaviors and
reproductive health outcomes we examined. CONCLUSIONS: Many sexual minority
girls, whether categorized according to sexual identity or partner gender, are
vulnerable to sexual and reproductive health risks. Attention to these risks is
needed to help sexual minority girls receive necessary services.
PMID- 25121823
TI - Highly luminescent salts containing well-shielded lanthanide-centered complex
anions and bulky imidazolium countercations.
AB - Four salts containing imidazolium cations and europium(III)- or terbium(III)
centered complex anions have been successfully synthesized from an ethanol/H2O
solution. The single-crystal X-ray diffraction analyses reveal that these
compounds have a common formula of [R][Ln(DETCAP)4] [R = 1-ethyl-3
methylimidazolium (C2mim), Ln = Eu (1) and Tb (2); R = 1-butyl-3
methylimidazolium (C4mim), Ln = Eu (3) and Tb (4); DETCAP = diethyl-2,2,2
trichloroacetylphosphoramidate], in which the lanthanide centers are chelated by
four chelating pseudo-beta-diketonate ligands (DETCAP)(-), forming the respective
complex anions. Their thermal behaviors and stabilities were also investigated to
study the role of the length of the side chain in the cations. Fluorescence
measurements at both room temperature and liquid-nitrogen temperature show that
these materials show intense characteristic europium(III) or terbium(III)
emissions and have long decay times. Their overall quantum yields were determined
to be in the range of 30-49%.
PMID- 25121822
TI - Reduction in fatalities, ambulance calls, and hospital admissions for road trauma
after implementation of new traffic laws.
AB - OBJECTIVES: We evaluated the public health benefits of traffic laws targeting
speeding and drunk drivers (British Columbia, Canada, September 2010). METHODS:
We studied fatal crashes and ambulance dispatches and hospital admissions for
road trauma, using interrupted time series with multiple nonequivalent comparison
series. We determined estimates of effect using linear regression models
incorporating an autoregressive integrated moving average error term. We used
neighboring jurisdictions (Alberta, Saskatchewan, Washington State) as external
controls. RESULTS: In the 2 years after implementation of the new laws,
significant decreases occurred in fatal crashes (21.0%; 95% confidence interval
[CI]=15.3, 26.4) and in hospital admissions (8.0%; 95% CI=0.6, 14.9) and
ambulance calls (7.2%; 95% CI=1.1, 13.0) for road trauma. We found a very large
reduction in alcohol-related fatal crashes (52.0%; 95% CI=34.5, 69.5), and the
benefits of the new laws are likely primarily the result of a reduction in
drinking and driving. CONCLUSIONS: These findings suggest that laws calling for
immediate sanctions for dangerous drivers can reduce road trauma and should be
supported.
PMID- 25121824
TI - Evolution at a different pace: distinctive phylogenetic patterns of cone snails
from two ancient oceanic archipelagos.
AB - Ancient oceanic archipelagos of similar geological age are expected to accrue
comparable numbers of endemic lineages with identical life history strategies,
especially if the islands exhibit analogous habitats. We tested this hypothesis
using marine snails of the genus Conus from the Atlantic archipelagos of Cape
Verde and Canary Islands. Together with Azores and Madeira, these archipelagos
comprise the Macaronesia biogeographic region and differ remarkably in the
diversity of this group. More than 50 endemic Conus species have been described
from Cape Verde, whereas prior to this study, only two nonendemic species,
including a putative species complex, were thought to occur in the Canary
Islands. We combined molecular phylogenetic data and geometric morphometrics with
bathymetric and paleoclimatic reconstructions to understand the contrasting
diversification patterns found in these regions. Our results suggest that species
diversity is even lower than previously thought in the Canary Islands, with the
putative species complex corresponding to a single species, Conus guanche. One
explanation for the enormous disparity in Conus diversity is that the amount of
available habitat may differ, or may have differed in the past due to eustatic
(global) sea level changes. Historical bathymetric data, however, indicated that
sea level fluctuations since the Miocene have had a similar impact on the
available habitat area in both Cape Verde and Canary archipelagos and therefore
do not explain this disparity. We suggest that recurrent gene flow between the
Canary Islands and West Africa, habitat losses due to intense volcanic activity
in combination with unsuccessful colonization of new Conus species from more
diverse regions, were all determinant in shaping diversity patterns within the
Canarian archipelago. Worldwide Conus species diversity follows the well
established pattern of latitudinal increase of species richness from the poles
towards the tropics. However, the eastern Atlantic revealed a striking pattern
with two main peaks of Conus species richness in the subtropical area and
decreasing diversities toward the tropical western African coast. A Random
Forests model using 12 oceanographic variables suggested that sea surface
temperature is the main determinant of Conus diversity either at continental
scales (eastern Atlantic coast) or in a broader context (worldwide). Other
factors such as availability of suitable habitat and reduced salinity due to the
influx of large rivers in the tropical area also play an important role in
shaping Conus diversity patterns in the western coast of Africa.
PMID- 25121826
TI - Folate ligand anchored liquid crystal microdroplets emulsion for in vitro
detection of KB cancer cells.
AB - A KB cancer cell-selective, liquid crystal microdroplets emulsion is prepared
using folic acid-conjugated block copolymers (PS-b-PAA-FA) and sodium dodecyl
sulfate (SDS) as a mediator to induce configurational transitions in 4-cyano-4'
pentylbiphenyl (5CB) liquid crystal microdroplets emulsion. The prepared liquid
crystal microdroplets emulsion has shown a configurational transition from radial
to bipolar on interacting with KB cancer cells, but no transition from radial to
bipolar configuration is observed when liquid crystal microdroplets emulsion was
allowed to interact with other normal cells such as fibroblast and osteoblast.
The KB cancer cell selectivity of liquid crystal microdroplets emulsion has been
considered due to the presence of KB cancer cell folate receptor-specific ligand
(FA) at the surface of liquid crystal microdroplets, which allowed liquid crystal
microdroplets to interact specifically with KB cancer cells. The ligand-receptor
interactions have been considered responsible for triggering the configurational
transitions from radial to bipolar in liquid crystal microdroplets emulsion.
Thus, folate ligand anchored liquid crystal microdroplets emulsion has shown a
potential to be used for in vitro detection of KB cancer cells in the early stage
of tumor development.
PMID- 25121825
TI - Genetic contribution to postpartum haemorrhage in Swedish population: cohort
study of 466,686 births.
AB - OBJECTIVE: To investigate the familial clustering of postpartum haemorrhage in
the Swedish population, and to quantify the relative contributions of genetic and
environmental effects. DESIGN: Register based cohort study. SETTING: Swedish
population (multi-generation and medical birth registers). MAIN OUTCOME MEASURE:
Postpartum haemorrhage, defined as >1000 mL estimated blood loss. PARTICIPANTS:
The first two live births to individuals in Sweden in 1997-2009 contributed to
clusters representing intact couples (n = 366,350 births), mothers with separate
partners (n = 53,292), fathers with separate partners (n = 47,054), sister pairs
(n = 97,228), brother pairs (n = 91,168), and mixed sibling pairs (n = 177,944).
METHODS: Familial clustering was quantified through cluster specific tetrachoric
correlation coefficients, and the influence of potential sharing of known risk
factors was evaluated with alternating logistic regression. Relative
contributions of genetic and environmental effects to the variation in liability
for postpartum haemorrhage were quantified with generalised linear mixed models.
RESULTS: The overall prevalence of postpartum haemorrhage after vaginal
deliveries in our sample was 4.6%. Among vaginal deliveries, 18% (95% confidence
interval 9% to 26%) of the variation in postpartum haemorrhage liability was
attributed to maternal genetic factors, 10% (1% to 19%) to unique maternal
environment, and 11% (0% to 26%) to fetal genetic effects. Adjustment for known
risk factors only partially explained estimates of familial clustering,
suggesting that the observed shared genetic and environmental effects operate in
part through pathways independent of known risk factors. There were similar
patterns of familial clustering for both of the main subtypes examined (atony and
retained placenta), though strongest for haemorrhage after retained placenta.
CONCLUSIONS: There is a maternal genetic predisposition to postpartum
haemorrhage, but more than half of the total variation in liability is
attributable to factors that are not shared in families.
PMID- 25121828
TI - A single practice's experience of NHS 111.
PMID- 25121829
TI - Role of desorption kinetics in the rhamnolipid-enhanced biodegradation of
polycyclic aromatic hydrocarbons.
AB - The main aim of this study was to investigate the effect of a rhamnolipid
biosurfactant on biodegradation of (14)C-labeled phenanthrene and pyrene under
desorption-limiting conditions. The rhamnolipid caused a significant
solubilization and enhanced biodegradation of PAHs sorbed to soils. The
enhancement was, however, negatively influenced by experimental conditions that
caused an enrichment of slow desorption fractions. These conditions included
aging, a higher organic matter content in soil, and previous extraction with
Tenax to remove the labile-desorbing chemical. The decline in bioavailability
caused by aging on sorbed (14)C-pyrene was partially reversed by rhamnolipids,
which enhanced mineralization of the aged compound, although not so efficiently
like with the unaged chemical. This loss in biosurfactant efficiency in promoting
biodegradation can be explained by intra-aggregate diffusion of the pollutant
during aging. We suggest that rhamnolipid can enhance biodegradation of soil
sorbed PAHs by micellar solubilization, which increase the cell exposure to the
chemicals in the aqueous phase, and partitioning into soil organic matter, thus
enhancing the kinetics of slow desorption. Our study show that rhamnolipid can
constitute a valid alternative to chemical surfactants in promoting the
biodegradation of slow desorption PAHs, which constitutes a major bottleneck in
bioremediation.
PMID- 25121827
TI - Systemic injection of CD34(+)-enriched human cord blood cells modulates
poststroke neural and glial response in a sex-dependent manner in CD1 mice.
AB - Stroke in the developing brain is an important cause of neurological morbidity.
We determined the impact of human cord blood-derived CD34(+)-enriched mononuclear
cells (CBSC) intraperitoneally injected 48 h after an ischemic stroke at
postnatal day 12 by evaluating poststroke neurogenic niche proliferation, glial
response, and recovery in CD1 mice. Percent brain atrophy was quantified from
Nissl-stained sections. Density of BrdU, Iba-1, and GFAP staining were quantified
in the dentate gyrus and the subventricular zone (SVZ). Immunohistochemistry for
human nuclear antibody, human mitochondrial antibody, and human CD34(+) cells was
done on injured and uninjured brains from CBSC- and vehicle-treated mice.
Developmental neurobehavioral milestones were evaluated pre- and post-treatment.
No significant differences in stroke severity were noted between CBSC and vehicle
treated injured animals. With a 1*10(5) CBSC dose, there was a significant
increase in subgranular zone (SGZ) proliferation in the CBSC-versus vehicle
treated stroke-injured male mice. SVZ glial fibrillary acidic protein (GFAP)
expression was increased contralaterally in injured females treated with CBSC but
suppressed in injured males. Significant negative correlations between severity
of the stroke-injury and spleen weights, and between spleen weights and SGZ
proliferation, and a positive correlation between GFAP expression and severity of
brain injury were noted in the vehicle-treated injured mice but not in the CBSC
treated mice. GFAP expression and SVZ proliferation were positively correlated.
In conclusion, neurogenic niche proliferation and glial brain responses to CBSC
after neonatal stroke may involve interactions with the spleen and are sex
dependent.
PMID- 25121830
TI - The complete mitochondrial DNA of white shark (Carcharodon carcharias) from Isla
Guadalupe, Mexico.
AB - The Isla Guadalupe white shark mitochondrial structure is similar to the one
previously reported for a white shark individual from Taiwan with a total length
of 16,745 and 16,742 bp respectively; the base composition of the genomes was as
follow A (30.60%), T (28.67%), C (26.86%) and G (13.87%), contains 13 protein
coding genes and 24 tRNA genes and the non-coding control region. The tRNA genes
range from 70-72 bp. Gene order is the same as in other vertebrates and teleosts.
PMID- 25121831
TI - The comparison of two complete mitochondrial genomes of Pseudobagrus ondon
(Siluriformes, Bagridae).
AB - The complete mitochondrial genome of Pseudobagrus ondon collected from the
Qiantang River in Zhejiang Province was determined in this study with polymerase
chain reaction. It contained 22 tRNA genes, 13 protein-coding genes, 2 rRNAs and
a control region with the base composition 31.03% A, 27.92% C, 25.78% T and
15.27% G. It shared the arrangement pattern that was identical with most
vertebrates. Here we compared the complete mitochondrial genome with another
Pseudobagrus ondon species has been sequenced before discovering some differences
between the two entities belong to the same species. The complete genome of the
one in this study was 16,531 bp in length but the other was 16,534 bp. The
variable sites and the genetic distances between them were 105 bp and 0.7%,
respectively. There was 79 variable sites occurred in the protein-coding genes
except that gene ATP8 and ND3 were the same sequences in the two mitogenomes.
Considering that relatively little work has been done on the fishes of
Pseudobagrus, we hope this study could make some contribution for the
phylogenetic relationships of this group of fishes.
PMID- 25121832
TI - DNA-barcoding of perch-like fishes (Actinopterygii: Perciformes) from far-eastern
seas of Russia with taxonomic remarks for some groups.
AB - The analysis of variation among 203 nucleotide sequences of Co-1 gene (DNA
barcode) for 45 species, 31 genera and 7 families of the order Perciformes from
the Far Eastern seas of Russia has been performed. As a result, 42 species
(93.3%) can be unambiguously identified using molecular DNA-barcode at Co-1,
whereas more variable markers are required for other species (6.7%): Stichaeus
grigorjewi, S. nozawae, and Lumpenus sagitta. The latter includes as well 2
morphologically distinct (by number of vertebrae) but genetically unresolved
species, L. sagitta (Sea of Okhotsk) and L. fabricii (Bering Sea). In addition,
within this genus morphologically poorly characterized but genetically well
distinguished cryptic species has been detected. Amphi-Pacific distribution is in
question relative to L. sagitta. Cryptic diversity was observed in the genus
Ammodytes.
PMID- 25121833
TI - Evolutionary history and population genetic structure of the endemic tree frog
Hyla tsinlingensis (Amphibia: Anura: Hylidae) inferred from mitochondrial gene
analysis.
AB - The influence of topography and Pleistocenic climatic fluctuations on the
population genetic structure of amphibians in the Tsinling-Dabieshan Mountains of
China is poorly investigated. Hyla tsinlingensis is a tree frog endemic to the
Tsinling-Dabieshan Mountains, with a restricted and patchy distribution that is
currently shrinking. We speculated on the evolutionary history of amphibians in
this region by studying the population genetic structure of H. tsinlingensis.
Using a total of 212 samples, 32 haplotypes and four haplogroups were found in
the present study. Population genetic structure showed significant
differentiation (F(ST)) between most populations of H. tsinlingensis in the
Tsinling-Dabieshan Mountains. An analysis of molecular variance (AMOVA) suggested
that most of the observed genetic variation occurs between the two regions (the
Tsinling and Dabieshan Mountains). Mantel tests indicated that the genetic
divergence was induced through isolation by distance. Using Monmonier's maximum
difference algorithm to predict the genetic barrier, two putative barriers in
gene flow that separate lineages of H. tsinlingensis were identified. Mismatch
distribution and neutrality tests found a sudden population expansion in all
haplogroups except the Tsinling population and total population. This population
expansion was identified between 0.5 Myr to 0.1 Myr (Quaternary) by Bayesian
skyline plot (BSP). Divergence dating indicated the divergence time between the
Tsinling population and Dabieshan population to be 3.26 MYA (Pliocene). In
conclusion, the topography of the Tsinling and Dabieshan Mountains exerts a
significant impact on the population genetic structure of H. tsinlingensis, and
climatic oscillations during glacial periods in the Quaternary affected the
distribution of H. tsinlingensis.
PMID- 25121834
TI - Complete mitochondrial genome of the Antarctic bullhead notothen, Notothenia
coriiceps (Perciformes, Nototheniidae).
AB - The complete sequence of the mitochondrial genome of Notothenia coriiceps was
obtained by genome assembly. The complete sequence was determined to be 18,347
base pairs in length and to contain 13 protein-coding genes, 22 tRNA genes, 2
rRNA genes, and 2 control regions. Of the thirteen protein-coding genes, two
genes (cox1 and atp6) had GTG start codons, and six genes (nad2, cox2, cox3,
nad3, nad4, and cytb) had incomplete stop codons that require the post
transcriptional addition of A bases. The base composition of the mitogenome was
26.3% A, 27.6% T, 17.5% G, and 28.5% C.
PMID- 25121835
TI - The complete mitochondrial DNA of the bay snook, Petenia splendida, a native
Mexican cichlid.
AB - The mitogenome of the tenguayaca, Petenia splendida (GenBank accession number
KJ914664) has a total length of 16,518 bp, and the arrangement consist of 15
protein-coding genes, 2 ribosomal RNA (rRNA) genes and 22 transfer RNA (tRNA)
genes. Gene order was equal to the mitogenomes of other new world cichlids.
PMID- 25121836
TI - Optical temperature sensing based on the near-infrared emissions from Nd3+/Yb3+
codoped CaWO4.
AB - Under a 980 nm diode laser excitation, the near-infrared (NIR) emissions from
Nd3+:4F7/2, 4F5/2, and 4F3/2 states in Nd3+/Yb3+ codoped CaWO4 powder were
studied at temperatures ranging from 303 to 873 K. As the temperature increased,
the NIR luminescence intensity was significantly enhanced and nearly 190-fold
enhancement was achieved at 873 K compared with that at 303 K. By using the
fluorescence intensity ratio technique, the thermometry behaviors through the NIR
emissions were investigated. The results illustrate that the sensitivity and the
accuracy achieved here are much higher than temperature sensors based on other
rare earth ion doped materials.
PMID- 25121837
TI - Numerical analysis of efficient light extraction with an elliptical solid
immersion lens.
AB - We introduce and analyze a design concept based on nonspherical solid immersion
lens (SIL) geometry. We find via finite difference time domain (FDTD) simulations
that elliptical solid immersion lenses (eSILs) exhibit a notably improved
emission directionality compared to the standard SIL design. Large light
collection efficiencies are achieved even for small numerical apertures (NAs).
For example, using a NA as low as 0.3, over 65% of the total light emitted by a
dipole can be collected.
PMID- 25121839
TI - Designing metal hemispheres on silicon ultrathin film solar cells for plasmonic
light trapping.
AB - We systematically investigate the design of two-dimensional silver (Ag)
hemisphere arrays on crystalline silicon (c-Si) ultrathin film solar cells for
plasmonic light trapping. The absorption in ultrathin films is governed by the
excitation of Fabry-Perot TEMm modes. We demonstrate that metal hemispheres can
enhance absorption in the films by (1) coupling light to c-Si film waveguide
modes and (2) exciting localized surface plasmon resonances (LSPRs). We show that
hemisphere arrays allow light to couple to fundamental TEm and TMm waveguide
modes in c-Si film as well as higher-order versions of these modes. The near
field light concentration of LSPRs also may increase absorption in the c-Si film,
though these resonances are associated with significant parasitic absorption in
the metal. We illustrate how Ag plasmonic hemispheres may be utilized for light
trapping with 22% enhancement in short-circuit current density compared with that
of a bare 100 nm thick c-Si ultrathin film solar cell.
PMID- 25121838
TI - Continuously tuning effective refractive index based on thermally controllable
magnetic metamaterials.
AB - By employing a thermally active magnetic material, we theoretically design a kind
of electromagnetic metamaterial with intrinsic magnetic response, termed magnetic
metamaterial (MM). The retrieved effective electric permittivity epsilon(eff) and
magnetic permeability MU(eff) exhibit a nearly continuous transition from double
negative to double zero, and then to double positive by controlling the
temperature, indicating a flexible tunability of the effective refractive index.
The beam splitting, collimation, focusing, and total reflection are achieved at
different typical temperatures. Most importantly, with the MM implemented under a
gradient temperature, a gradient negative-zero-positive index metamaterial
(NZPIM) can possibly be realized, thus providing a new platform to study wave
features in NZPIM.
PMID- 25121840
TI - Low-threshold Brillouin laser at 2 MUm based on suspended-core chalcogenide
fiber.
AB - We present, to the best of our knowledge, the first demonstration of a 2 MUm
Brillouin laser based on a thulium-doped fiber pump and a chalcogenide fiber. A
short 1.5 m piece of suspended-core chalcogenide As38Se62 fiber is employed as a
gain medium, taking advantage of its small effective mode area and high Brillouin
gain coefficient. A record-low lasing threshold of 52 mW is achieved, which is
about 10 times lower than previously demonstrated in silica fiber cavities.
PMID- 25121841
TI - Prospects for diode-pumped alkali-atom-based hollow-core photonic-crystal fiber
lasers.
AB - By employing large hollow-core Kagome fiber in a double-clad configuration, the
performance of a potentially rubidium vapor-based fiber laser is explored. The
absorbed power and laser efficiency versus pump power are calculated utilizing a
simple laser model. Our results show that a Kagome-based high-power fiber laser
is feasible provided that the value of the collisional fine-structure mixing rate
will be elevated by increasing the ambient temperature or by increasing the
helium pressure.
PMID- 25121842
TI - Post-filament self-trapping of ultrashort laser pulses.
AB - Laser filamentation is understood to be self-channeling of intense ultrashort
laser pulses achieved when the self-focusing because of the Kerr nonlinearity is
balanced by ionization-induced defocusing. Here, we show that, right behind the
ionized region of a laser filament, ultrashort laser pulses can couple into a
much longer light channel, where a stable self-guiding spatial mode is sustained
by the saturable self-focusing nonlinearity. In the limiting regime of negligibly
low ionization, this post-filamentation beam dynamics converges to a large-scale
beam self-trapping scenario known since the pioneering work on saturable self
focusing nonlinearities.
PMID- 25121843
TI - Plasmonic waveguides cladded by hyperbolic metamaterials.
AB - Strongly anisotropic media with hyperbolic dispersion can be used for claddings
of plasmonic waveguides (PWs). In order to analyze the fundamental properties of
such waveguides, we analytically study 1D waveguides arranged from a hyperbolic
metamaterial (HMM) in a HMM-Insulator-HMM (HIH) structure. We show that HMM
claddings give flexibility in designing the properties of HIH waveguides. Our
comparative study on 1D PWs reveals that HIH-type waveguides can have a higher
performance than MIM or IMI waveguides.
PMID- 25121844
TI - Improved configuration and reduction of phase noise in a narrow linewidth
ultrawideband optical RF source.
AB - In this Letter, we report on the improved configuration of a widely tunable
optical RF generation system, particularly for the generation of low-frequency
RF, as well as the reduction of phase noise in that same system. Using an
amplitude modulator, a simplified system design was demonstrated with fewer
components and improved phase noise performance, especially at RF frequencies
below ~36 GHz. Excess phase noise due to acoustic vibrations of the optical
fibers was also successfully eliminated by mechanical isolation. A minimum phase
noise of -124 dBc/Hz at 10 kHz offset was demonstrated at 4 GHz.
PMID- 25121846
TI - Nonlinear switching in a two-concentric-core chalcogenide glass optical fiber for
passively mode-locking a fiber laser.
AB - We propose an all-fiber mode-locking device, which operates based on nonlinear
switching in a novel two-concentric-core fiber structure. The design is
particularly attractive given the ease of fabrication and coupling to other
components in a mode-locked fiber laser cavity. The nonlinear switching in this
coupler is studied, and the relative power transmission is obtained. The analysis
shows that this nonlinear switch is practical for mode-locking fiber lasers and
is forgiving to fabrication errors.
PMID- 25121845
TI - 152 W average power Tm-doped fiber CPA system.
AB - A high-power thulium (Tm)-doped fiber chirped-pulse amplification system emitting
a record compressed average output power of 152 W and 4 MW peak power is
demonstrated. This result is enabled by utilizing Tm-doped photonic crystal
fibers with mode-field diameters of 35 MUm, which mitigate detrimental
nonlinearities, exhibit slope efficiencies of more than 50%, and allow for
reaching a pump-power-limited average output power of 241 W. The high-compression
efficiency has been achieved by using multilayer dielectric gratings with
diffraction efficiencies higher than 98%.
PMID- 25121847
TI - Photo-aligned ferroelectric liquid crystals in microchannels.
AB - In this Letter we disclose a method to realize a good alignment of ferroelectric
liquid crystals (FLCs) in microchannels, based on photo-alignment. The sulfonic
azo dye used in our research offers variable anchoring energy depending on the
irradiation energy and thus provides good control on the FLC alignment in
microchannels. The good FLC alignment has been observed only when anchoring
energy normalized to the capillary diameter is less than the elastic energy of
the FLC helix. The same approach can also be used for the different
microstructures viz. photonic crystal fibers, microwaveguides, etc. which gives
an opportunity for designing a photonic devices based on FLC.
PMID- 25121848
TI - Achromatic wide-view circular polarizers for a high-transmittance vertically
aligned liquid crystal cell.
AB - We propose an optical compensation scheme through which we can eliminate the off
axis light leakage in a vertically-aligned liquid crystal cell with circular
polarizers. In this scheme, four uniaxial films with complementary dispersion
characteristics are used to compensate one another, resulting in achromatic
effective phase retardation for off-axis angles. By using the proposed optical
compensation, a contrast ratio higher than 2000:1 can be realized over the entire
55 degrees viewing cone in a multi-domain vertical-alignment liquid crystal cell
with circular polarizers.
PMID- 25121849
TI - Dual spectral-band interferometry for spatio-temporal characterization of high
power femtosecond lasers.
AB - We present and demonstrate a technique called RED-SEA TADPOLE for the spatio
temporal characterization of high peak power femtosecond lasers. It retains the
basic principle of an existing method, where a scanning monomode fiber is
utilized in an interferometric scheme to measure the spectral amplitude and phase
at all points across an ultrashort laser beam. We combine this approach with dual
spectral-band interferometry, to correct for all phase errors occurring in this
interferometer, thus allowing for the simultaneous measurement of the beam
wavefront and pulse front in a collimated beam of large diameter. The generic
phase correction procedure implemented here can also be extended to other fiber
optic device applications sensitive to phase fluctuations.
PMID- 25121850
TI - Size-controlled Ge nanostructures for enhanced Er3+ light emission.
AB - The potential of Ge nanoparticles (NPs) embedded in Al2O3 with tunable effective
optical bandgap values in the range of 1.0-3.3 eV to induce enhanced Er3+ light
emission is investigated. We demonstrate nonresonant indirect excitation of the
Er3+ ions mediated by the Ge NPs at room temperature. Efficient Er3+ light
emission enhancement is obtained for Ge NPs with large effective optical bandgaps
in the range of 1.85 to 2.8 eV. The coupled Ge NP-Er emission shows a negligible
thermal quenching from 10 K to room temperature that is related to Er3+ de
excitation through thermally activated defect states.
PMID- 25121851
TI - Optical feedback frequency stabilized cavity ring-down spectroscopy.
AB - We introduce optical feedback frequency stabilized cavity ring-down spectroscopy
(OFFS-CRDS), a near-shot-noise-limited technique that combines kilohertz
resolution with an absorption detection sensitivity of 5*10(-13) cm(-1) Hz(-1/2).
Its distributed feedback laser source is stabilized to a highly stable V-shaped
reference cavity by optical feedback and fine-tuned by means of single-sideband
modulation. The stability of this narrow laser is transferred to a ring-down (RD)
cavity using a new fibered Pound-Drever-Hall (PDH) locking scheme without a
dedicated electro-optic phase modulator, yielding several hundred RD events per
second. We demonstrate continuous coverage of more than 7 nm with a baseline
noise of 5*10(-12) cm(-1) and a dynamic range spanning six decades. With its
resonant intracavity light intensity on the order of 1 kW/cm2, the spectrometer
was used for observing a Lamb dip in a transition of carbon dioxide involving
four vibrational quanta. Saturating such a weak transition at 160 MUW input
power, OFFS-CRDS paves the way to Doppler-free molecular overtone spectroscopy
for precision measurements of hyperfine structures and pressure shifts.
PMID- 25121852
TI - Optical forces and torques on realistic plasmonic nanostructures: a surface
integral approach.
AB - We develop a novel formalism to calculate the optical forces and torques on
complex and realistic nanostructures by combining the surface integral equation
(SIE) technique with Maxwell's stress tensor. The optical force is calculated
directly on the scatterer surface from the currents obtained from the SIE, which
does not require an additional surface to evaluate Maxwell's stress tensor; this
is especially useful for intricate geometries such as plasmonic antennas. SIE
enables direct evaluation of forces from the surface currents very efficiently
and accurately for complex systems. As a proof of concept, we establish the
accuracy of the model by comparing the results with the calculations from the Mie
theory. The flexibility of the method is demonstrated by simulating a realistic
plasmonic system with intricate geometry.
PMID- 25121853
TI - Ultracompact silicon-on-insulator polarization rotator for polarization
diversified circuits.
AB - We present an ultracompact (15.3 MUm long) and high-efficiency silicon-on
insulator polarization rotator designed for polarization-diversified circuits.
The rotator is comprised of a bilevel-tapered TM0-to-TE1 mode converter and a
novel bent-tapered TE1-to-TE0 mode converter. The rotator has a simulated
polarization conversion loss lower than 0.2 dB and a polarization-extinction
ratio larger than 25 dB over a wavelength range of 80 nm around 1550 nm. The
rotator has a SiO2 top-cladding and can be fabricated in a CMOS-compatible
process.
PMID- 25121854
TI - Local spectroscopy of silver nanowire in different environments excited with a
halogen lamp.
AB - We report a propagation spectrum detection system in which one end of a plasmonic
silver nanowire is locally illuminated from a normal halogen lamp and the
scattered light is recorded spectroscopically at the other end. The system is
applied to investigate surface plasmon polariton-Fabry-Perot (SPP-FP) modes of
silver nanowires with different lengths at air-glass and oil-glass interfaces.
The generalized FP model is used to analyze the spectrum, which fits well with
the experimental results. The influence of nanowire length and environment on the
properties of the FP resonances is discussed. The propagation spectrum detection
system will find applications for integrated optical circuits and plasmonic
sensing.
PMID- 25121855
TI - GeSn/Ge multiquantum well photodetectors on Si substrates.
AB - Vertical incidence GeSn/Ge multiquantum well (MQW) pin photodetectors on Si
substrates were fabricated with a Sn concentration of 7%. The epitaxial structure
was grown with a special low temperature molecular beam epitaxy process. The Ge
barrier in the GeSn/Ge MQW was kept constant at 10 nm. The well width was varied
between 6 and 12 nm. The GeSn/Ge MQW structures were grown pseudomorphically with
the in-plane lattice constant of the Ge virtual substrate. The absorption edge
shifts to longer wavelengths with thicker QWs in agreement with expectations from
smaller quantization energies for the thicker QWs.
PMID- 25121856
TI - Generation of multiple sheets of light using spatial-filtering technique.
AB - We develop an optical system for generating multiple light sheets. This is
enabled by employing a special class of spatial filters in a cylindrical lens
geometry. The proposed binary filter placed at the back aperture of the
cylindrical lens results in the generation of a periodic transverse pattern
extending along the z axis (i.e., multiple light sheets). Experimental results
confirm the generation of multiple light sheets of thickness 6.6 MUm with an
intersheet spacing of 13.4 MUm. The proposed imaging technique may facilitate
three-dimensional imaging in nano-optics, fluorescence microscopy, and
nanobiology.
PMID- 25121857
TI - Refocusing criterion via sparsity measurements in digital holography.
AB - Several automatic approaches have been proposed in the past to compute the
refocus distance in digital holography (DH). However most of them are based on a
maximization or minimization of a suitable amplitude image contrast measure,
regarded as a function of the reconstruction distance parameter. Here we show
that, by using the sparsity measure coefficient regarded as a refocusing
criterion in the holographic reconstruction, it is possible to recover the focus
plane and, at the same time, establish the degree of sparsity of digital
holograms, when samples of the diffraction Fresnel propagation integral are used
as a sparse signal representation. We employ a sparsity measurement coefficient
known as Gini's index thus showing for the first time, to the best of our
knowledge, its application in DH, as an effective refocusing criterion.
Demonstration is provided for different holographic configurations (i.e., lens
and lensless apparatus) and for completely different objects (i.e., a thin pure
phase microscopic object as an in vitro cell, and macroscopic puppets)
preparation.
PMID- 25121858
TI - Transmission enhancement through square coaxial aperture arrays in metallic film:
when leaky modes filter infrared light for multispectral imaging.
AB - The diffractive behavior of arrays of square coaxial apertures in a gold layer is
studied. These structures exhibit a resonant transmission enhancement that is
used to design tunable bandpass filters for multispectral imaging in the 7-13 MUm
wavelength range. A modal analysis is used for this design and the study of their
spectral features. Thus we show that the resonance peak is due to the excitation
of leaky modes of the open photonic structure. Fourier transform infrared (FTIR)
spectrophotometry transmission measurements of samples deposited on Si substrate
show good agreement with numerical results and demonstrate angular tolerance of
up to 30 degrees of the fabricated filters.
PMID- 25121859
TI - Quantitative optical inspection of contact lenses immersed in wet cell using
swept source OCT.
AB - We demonstrate swept source optical coherence tomography (OCT) imaging of contact
lenses (CLs) in a wet cell and comprehensive quantitative characterization of CLs
from volumetric OCT datasets. The approach is based on a technique developed for
lens autopositioning and autoleveling enabled by lateral capillary interactions
between the wet cell wall and the lens floating on the liquid surface. The
demonstrated OCT imaging has enhanced contrast due to the application of a
scattering medium and it improves visualization of both CL interfaces and edges.
We also present precise and accurate three-dimensional metrology of soft and
rigid CLs based on the OCT data. The accuracy and precision of the extracted lens
parameters are compared with the manufacturer's specifications. The presented
methodology facilitates industrial inspection methods of the CLs.
PMID- 25121861
TI - 100 kHz, 100 ms, 400 J burst-mode laser with dual-wavelength diode-pumped
amplifiers.
AB - The burst duration of an all-diode-pumped burst-mode laser is extended to 100 ms
and 100 kHz (10,000 pulses) by utilizing dual-wavelength diode pumping. Total
energies of 225 J at 10 kHz and 400 J at 100 kHz are achieved during the 100 ms
burst period at 1064 nm. This represents an order-of-magnitude increase in the
number of pulses compared with prior work, while maintaining similar or higher
pulse energies. Amplitude tailoring of each pulse is used to flatten the burst
profile, reducing the standard deviation in pulse energy over the 100 ms burst
from 3.7% to 2.1% with a burst-to-burst standard deviation of 0.8%.
PMID- 25121862
TI - Chaotic behavior of cavity solitons induced by time delay feedback.
AB - We investigate spatiotemporal dynamics of cavity solitons in a broad area
vertical-cavity surface-emitting laser with saturable absorption subject to time
delayed optical feedback. We show that the inclusion of feedback leads to a
period doubling route to chaos of spatially localized light structures.
PMID- 25121860
TI - Handheld photoacoustic microscopy to detect melanoma depth in vivo.
AB - We developed handheld photoacoustic microscopy (PAM) to detect melanoma and
determine tumor depth in nude mice in vivo. Compared to our previous PAM system
for melanoma imaging, a new light delivery mechanism is introduced to improve
light penetration. We show that melanomas with 4.1 and 3.7 mm thicknesses can be
successfully detected in phantom and in in vivo experiments, respectively. With
its deep melanoma imaging ability and handheld design, this system can be tested
for clinical melanoma diagnosis, prognosis, and surgical planning for patients at
the bedside.
PMID- 25121863
TI - Optically pumped distributed feedback dye lasing with slide-coated TiO2 inverse
opal slab as Bragg reflector.
AB - We demonstrate an optical amplification of organic dye within a TiO2 inverse-opal
(IO) distributed feedback (DFB) reflector prepared by a slide-coating method.
Highly reflective TiO2 IO film was fabricated by slide coating the binary aqueous
dispersions of polystyrene microspheres and charge-stabilized TiO2 nanoparticles
on a glass slide and subsequently removing the polymer-opal template. TiO2 IO
film was infiltrated, in turn, with the solutions of DCM, a fluorescent dye in
various solvents with different indices of refraction. Optical pumping by
frequency-doubled Nd:YAG laser resulted in amplified spontaneous emission in each
dye solution. In accordance with the semi-empirical simulation by the FDTD
method, DCM in ethanol showed the best emission/stopband matching for the TiO2 IO
film used in this study. Therefore, photo excitation of a DCM/ethanol cavity
showed a single-mode DFB lasing at 640 nm wavelength at moderate pump energy.
PMID- 25121864
TI - Electron beam position monitor for a dielectric microaccelerator.
AB - We report the fabrication and first demonstration of an electron beam position
monitor for a dielectric microaccelerator. This device is fabricated on a fused
silica substrate using standard optical lithography techniques and uses the
radiated optical wavelength to measure the electron beam position with a
resolution of 10 MUm, or 7% of the electron beam spot size. This device also
measures the electron beam spot size in one dimension.
PMID- 25121865
TI - Effect and elimination of alignment error in an optical fiber current sensor.
AB - This Letter demonstrates the effect and elimination of alignment error in an
optical fiber current sensor. An optical model is built to illustrate the effect
of alignment error, which does not induce zero drift and has a large effect on
output accuracy. The total alignment error and modulation angle of the
polarization controller are defined as k and theta, respectively. Parameter t is
equal to 2theta-2k. An elimination method of the error k is proposed, which
corrects the angle theta to keep parameter t at 90 deg. This method avoids the
measurement of all splice angles separately. Its feasibility is shown by
simulation results. In addition, the measurement method and conditions of
parameter t are presented. The final t is about 90.24 deg. Furthermore, the
effectiveness of the proposed elimination method is proven by a performance test.
PMID- 25121866
TI - Efficient Q-switched Ho:GdVO4 laser resonantly pumped at 1942 nm.
AB - An efficient 2 MUm room-temperature Q-switched Ho:GdVO4 laser end-pumped by a
1942 nm Tm-fiber laser is demonstrated. To our knowledge, this is the first
report of Q-switched performance of Ho:GdVO4 crystal. A maximum CW output power
of 6.85 W under the absorbed pump power of 24.1 W was obtained with a slope
efficiency of 39.5% at a temperature of 17 degrees C. With the same absorbed pump
power, a maximum output energy per pulse of about 0.9 mJ and minimum pulse width
of 4.7 ns were obtained at the pulsed repetition frequency (PRF) of 5 kHz,
corresponding to a peak power of approximately 187.2 kW.
PMID- 25121867
TI - Photonic generation of triangular pulses based on nonlinear polarization rotation
in a highly nonlinear fiber.
AB - We propose a novel method to generate triangular pulses based on the nonlinear
polarization rotation (NPR) effect in a highly nonlinear fiber. A continuous wave
probe beam is polarization-rotated by an intensity-modulated control beam via the
NPR effect. A polarization-division-multiplexing emulator is exploited to split
the probe beam into two orthogonally polarized states with imbalanced time delay.
After detection by a photodetector, a 90 degrees microwave phase shifter is used
to compensate the phases of the fundamental and the third-order harmonic
components in order to generate triangular pulses. Triangular pulses at 5 and 6
GHz with full duty cycles are experimentally generated. The root mean square
errors between the generated and the simulated waveforms are 3.6e-4 and 1e-4 for
triangular pulses at 5 and 6 GHz, respectively.
PMID- 25121868
TI - Controllable continuous-wave Nd:YVO4 self-Raman lasers using intracavity adaptive
optics.
AB - A controllable self-Raman laser using an adaptive optics (AO)-based control loop
featuring an intracavity deformable mirror is reported. This method has the
potential to alleviate thermal lensing within the Raman and laser gain media, and
enable solid-state Raman lasers to reach new power levels. A proof-of-concept
experiment using a Nd:YVO4 self-Raman laser and resulting in 18% enhancement of
the first Stokes output power is reported. Moreover, wavelength selection between
two Raman laser outputs (lambda=1109 and 1176 nm) emanating from the 379 and 893
cm(-1) Raman shifts of YVO4, respectively, was achieved using this AO technique.
PMID- 25121869
TI - Compact 4.7 W, 18.3% wall-plug efficiency green laser based on an electrically
pumped VECSEL using intracavity frequency doubling.
AB - We have demonstrated a compact, 4.7 W green laser based on an electrically pumped
vertical external-cavity surface emitting laser through intracavity frequency
doubling. The overall wall-plug efficiency (electrical to green) was 18.3%. The
power fluctuations were measured to be +/-1.4% over a 2 h time period.
PMID- 25121870
TI - Fiber-optic ferrule-top nanomechanical resonator with multilayer graphene film.
AB - Compact ferrule-top nanomechanical resonators with multilayer graphene (MLG)
diaphragms as vibrating elements are demonstrated. The resonators comprise a
suspended MLG film supported by a ceramic ferrule with a bore diameter of ~125
MUm. The mechanical resonance of the graphene film is excited and detected by an
all-fiber optical interrogation system. Based on a beam-shape graphene mechanical
resonator, a force sensitivity of ~3.8 fN/Hz1/2 was theoretically predicted. The
integration of nanomechanical graphene film with optical fiber simplifies the
excitation and interrogation of the resonator and would allow the development of
practical fiber-optic sensors for force, mass, and pressure measurements.
PMID- 25121871
TI - Binocular open-view instrument to measure aberrations and pupillary dynamics.
AB - We have designed and built a binocular Hartmann-Shack wave-front sensor using a
single microlens array and camera for real-time aberration measurement of both
eyes in an open-view configuration. Furthermore, the use of a long wavelength
(1050 nm) laser diode makes the illumination source completely invisible, so that
measurements can be unobtrusively performed while the subject stares at the
visual world under realistic conditions. The setup provides a large dynamic range
and simultaneous measurements of convergence, pupil size, accommodation, and
aberrations. The open-view design not only offers the possibility of measuring
the subject's ocular optics under natural conditions but also allows coupling the
device with other existing vision testing instruments and setups, which increases
its potential to become a powerful tool for different visual optics studies.
PMID- 25121872
TI - Speckle phase noise in coherent laser ranging: fundamental precision limitations.
AB - Frequency-modulated continuous-wave laser detection and ranging (FMCW LADAR)
measures the range to a surface through coherent detection of the backscattered
light from a frequency-swept laser source. The ultimate limit to the range
precision of FMCW LADAR, or any coherent LADAR, to a diffusely scattering surface
will be determined by the unavoidable speckle phase noise. Here, we demonstrate
the two main manifestations of this limit. First, frequency-dependent speckle
phase noise leads to a non-Gaussian range distribution having outliers that
approach the system range resolution, regardless of the signal-to-noise ratio.
These outliers are reduced only through improved range resolution (i.e., higher
optical bandwidths). Second, if the range is measured during a continuous lateral
scan across a surface, the spatial pattern of speckle phase is converted to
frequency noise, which leads to additional excess range uncertainty. We explore
these two effects and show that laboratory results agree with analytical
expressions and numerical simulations. We also show that at 1 THz optical
bandwidth, range precisions below 10 MUm are achievable regardless of these
effects.
PMID- 25121873
TI - Top-hat beam output with 100 MUJ temporally shaped narrow-bandwidth nanosecond
pulses from a linearly polarized all-fiber system.
AB - We report on an all-fiber system delivering more than 100 MUJ pulses with a top
hat beam output in the few nanoseconds regime at 10 kHz. The linearly polarized
flattened beam is obtained thanks to a 3-mm-long single-mode microstructured
fiber spliced to the amplifier's output.
PMID- 25121874
TI - Heterogeneously integrated III-V-on-silicon multibandgap superluminescent light
emitting diode with 290 nm optical bandwidth.
AB - A broadband superluminescent III-V-on-silicon light-emitting diode (LED) was
realized. To achieve the large bandwidth, quantum well intermixing and multiple
die bonding of InP on a silicon photonic waveguide circuit were combined for the
first time, to the best of our knowledge. The device consists of four sections
with different bandgaps, centered around 1300, 1380, 1460, and 1540 nm. The
fabricated LEDs were connected on-chip in a serial way, where the light generated
in the smaller bandgap sections travels through the larger bandgap sections. By
balancing the pump current in the four LEDs, we achieved 292 nm of 3 dB bandwidth
and an on-chip power of -8 dBm.
PMID- 25121876
TI - Parametric laser pulse shortening.
AB - We report simultaneous laser pulse shortening and wavelength conversion based on
spectral-temporal correlation in high-gain optical parametric generation (OPG).
By spectrally filtering the off-peak signal energy, we shortened a 560 ps pump
pulse at 1064 nm to an 80 ps signal pulse at 1.5 MUm from a 45 mm long PPLN
optical parametric generator with 60 MUJ pump energy from a passively Q-switched
Nd:YAG laser. Using the same technique, we further demonstrated a 3.6 time
shortened laser pulse at 1072 nm from noncollinearly phase matched OPG in a 44 mm
long lithium niobate crystal with 3 mJ amplified pump energy from the same Nd:YAG
laser.
PMID- 25121875
TI - Femtosecond pulse shaping enables detection of optical Kerr-effect (OKE) dynamics
for molecular imaging.
AB - We apply femtosecond pulse shaping to generate optical pulse trains that directly
access a material's nonlinear refractive index (n2) and can thus determine time
resolved optical Kerr-effect (OKE) dynamics. Two types of static pulse trains are
discussed: The first uses two identical fields delayed in time, plus a pump field
at a different wavelength. Time-resolved OKE dynamics are retrieved by monitoring
the phase of the interference pattern produced by the two identical fields in the
Fourier-domain (FD) as a function of pump-probe-time-delay (where the probe is
one of the two identical fields). The second pulse train uses three fields with
equal time delays, but with the center field phase shifted by pi/2. In this pulse
scheme, changes on a sample's nonlinear refractive index produce a new frequency
in the FD signal, which in turn yields background-free intensity changes in the
conjugate (time) domain and provides superior signal-to-noise ratios. The
demonstrated sensitivity improvements enable, for the first time to our
knowledge, molecular imaging based on OKE dynamics.
PMID- 25121877
TI - 3D-printed miniature gas cell for photoacoustic spectroscopy of trace gases.
AB - A new methodology for the development of miniature photoacoustic trace gas
sensors using 3D printing is presented. A near-infrared distributed feedback
(DFB) laser is used together with a polymer-based gas cell, off-the-shelf fiber
optic collimators, and a microelectromechanical system (MEMS) microphone to
measure acetylene at 1532.83 nm. The resonance behavior of the miniature gas cell
is analyzed using a theoretical and experimental approach, with a measured
resonance frequency of 15.25 kHz and a Q-factor of 15. A minimum normalized noise
equivalent absorption of 4.5*10(-9) W cm(-1) Hz(-1/2) is shown together with a
3sigma detection limit of 750 parts per billion (ppb) for signal averaging times
of 35 s. The fiber-coupled delivery and miniature cost-effective cell design
allows for use in multipoint and remote detection applications.
PMID- 25121878
TI - Opto-mechanical probe for combining atomic force microscopy and optical near
field surface analysis.
AB - We have developed a new easy-to-use probe that can be used to combine atomic
force microscopy (AFM) and scanning near-field optical microscopy (SNOM). We show
that, using this device, the evanescent field, obtained by total internal
reflection conditions in a prism, can be visualized by approaching the surface
with the scanning tip. Furthermore, we were able to obtain simultaneous AFM and
SNOM images of a standard test grating in air and in liquid. The lateral
resolution in AFM and SNOM mode was estimated to be 45 and 160 nm, respectively.
This new probe overcomes a number of limitations that commercial probes have,
while yielding the same resolution.
PMID- 25121879
TI - Suppression and splitting of modulational instability sidebands in periodically
tapered optical fibers because of fourth-order dispersion.
AB - We study the modulational instability induced by periodic variations of group
velocity dispersion in the proximity of the zero dispersion point. Multiple
instability peaks originating from parametric resonance coexist with the
conventional modulation instability because of fourth-order dispersion, which in
turn is suppressed by the oscillations of dispersion. Moreover, isolated unstable
regions appear in the space of parameters because of imperfect phase matching.
This confirms the dramatic effect of periodic tapering in the control and shaping
of MI sidebands in optical fibers.
PMID- 25121880
TI - Quantum correlation of fiber-based telecom-band photon pairs through standard
loss and random media.
AB - We study quantum correlation and interference of fiber-based telecom-band photon
pairs with one photon of the pair experiencing multiple scattering in a random
medium. We measure joint probability of two-photon detection for signal photon in
a normal channel and idler photon in a channel, which is subjected to two
independent conditions: standard loss (neutral density filter) and random media.
We observe that both conditions degrade the correlation of signal and idler
photons, and depolarization of the idler photon in random medium can enhance two
photon interference at certain relative polarization angles. Our theoretical
calculation on two-photon polarization correlation and interference as a function
of mean free path is in agreement with our experiment data. We conclude that
quantum correlation of a polarization-entangled photon pair is better preserved
than a polarization-correlated photon pair as one photon of the pair scatters
through a random medium.
PMID- 25121881
TI - Optimization of multicore fiber for high-temperature sensing.
AB - We demonstrate a novel high-temperature sensor using multicore fiber (MCF)
spliced between two single-mode fibers. Launching light into such fiber chains
creates a supermode interference pattern in the MCF that translates into a
periodic modulation in the transmission spectrum. The spectrum shifts with
changes in temperature and can be easily monitored in real time. This device is
simple to fabricate and has been experimentally shown to operate at temperatures
up to 1000 degrees C in a very stable manner. Through simulation, we have
optimized the multicore fiber design for sharp spectral features and high overall
transmission in the optical communications window. Comparison between the
experiment and the simulation has also allowed determination of the thermo-optic
coefficient of the MCF as a function of temperature.
PMID- 25121882
TI - Measurement of group velocity dispersion in a solid-core photonic crystal fiber
filled with a nematic liquid crystal.
AB - Liquid crystal-filled photonic crystal fibers (PCFs) are promising candidates for
electrically tunable integrated photonic devices. In this Letter, we present
group velocity measurements on such fibers. A large mode area PCF, LMA8, was
infiltrated with the liquid crystal mixture, E7. The measurements were performed
with an interferometric setup. The fiber exhibits several spectral transmission
windows in the visible wavelength regime that originate from the bandgap guiding
mechanism. The dispersion of these windows is very unusual compared to typical
fibers. Our measurements show that it can change from -2500 ps km(-1) nm(-1) to
+2500 ps km(-1) nm(-1) within a spectral range of only 15 nm. This leads to
multiple zero dispersion wavelengths in the visible wavelength range.
PMID- 25121883
TI - Ultrafast laser inscription of mid-IR directional couplers for stellar
interferometry.
AB - We report the ultrafast laser fabrication and mid-IR characterization (3.39 MUm)
of four-port evanescent field directional couplers. The couplers were fabricated
in a commercial gallium lanthanum sulfide glass substrate using sub-picosecond
laser pulses of 1030 nm light. Straight waveguides inscribed using optimal
fabrication parameters were found to exhibit propagation losses of ~0.8 dB.cm(
1). A series of couplers were inscribed with different interaction lengths, and
we demonstrate power-splitting ratios of between 8% and 99% for mid-IR light with
a wavelength of 3.39 MUm. These results clearly demonstrate that ultrafast laser
inscription can be used to fabricate high-quality evanescent field couplers for
future applications in astronomical interferometry.
PMID- 25121884
TI - Lattice plasmon resonance in core-shell SiO2/Au nanocylinder arrays.
AB - Core-shell SiO2/Au nanocylinder arrays (NCAs) are studied using finite-difference
time-domain simulations. The increase of height induces new surface plasmon
resonances along the nanocylinders, i.e., dipole and quadrupole modes. Orthogonal
coupling between superstrate diffraction order and the height-induced dipole mode
is observed, which could achieve a well-defined lattice plasmon mode even for
smaller NCAs in asymmetric environments. Electromagnetic field distribution has
been employed to determine the coupling origin. Radiative loss could also be
effectively suppressed in these core-shell NCAs, indicating the possibility of
future applications in fluorescence enhancement and nanolasers.
PMID- 25121885
TI - Comparison of T-matrix calculation methods for scattering by cylinders in optical
tweezers.
AB - The T-matrix method, or the T-matrix formulation of scattering, is a framework
for mathematically describing the scattering properties of an object as a linear
relationship between expansion coefficients of the incident and scattering fields
in a basis of vector spherical wave functions (VSWFs). A variety of methods can
be used to calculate the T-matrix. We explore the applicability of the extended
boundary condition method (EBCM) and point matching (PM) method to calculate the
T-matrix for scattering by cylinders in optical tweezers and hence the optical
force acting on them. We compare both methods with the discrete-dipole
approximation (DDA) to measure their accuracy for different sizes and aspect
ratios (ARs) for Rayleigh and wavelength-size cylinders. We determine range of
sizes and ARs giving errors below 1% and 10%. These results can help researchers
choose the most efficient method to calculate the T-matrix for nonspherical
particles with acceptable accuracy.
PMID- 25121886
TI - Time-domain coherent anti-Stokes Raman scattering in terms of the time-delayed
Yuratich equation.
AB - We show that the increasingly popular nonlinear optical technique of time-domain
coherent anti-Stokes Raman scattering (CARS), which is often viewed from the
dynamical perspective of the semiclassical time-dependent third-order
polarization, can also be studied by means of the time-delayed version of the
Yuratich equation, so popular in traditional frequency-domain CARS. The method
proves successful in explaining experimental results that are otherwise treated
by means of numerical methods only.
PMID- 25121888
TI - High-speed silicon modulator with band equalization.
AB - Electro-optic modulation up to 70 Gbit/s has been demonstrated using a silicon
Mach-Zehnder modulator with a bias voltage of -1.5 V. In a wide frequency range
from DC, an increasing input impedance of the modulator was designed to equalize
its electro-optic frequency response. Without a bias voltage, the 3 dB bandwidth
was measured as 35 GHz and it is predicted to be as high as 55 GHz at -3 V bias.
Frequency responses of the modulator operated with counter-propagating waves were
tested to verify the proposed prediction model.
PMID- 25121887
TI - Interferometric fiber-optic bending/nano-displacement sensor using plastic dual
core fiber.
AB - We demonstrate an interferometric fiber-optic bending/nano-displacement sensor
based on a plastic dual-core fiber. The light coupled into the two fiber cores is
first guided along the fiber, and then reflected by the mirror coated at the
fiber end. Reflected light coming out of the fiber produces interference that
shifts as the fiber bends. The interference shift is interrogated using a slit
and a photodetector. The resolution of our sensor is ~3*10(-4) m(-1) for sensing
the bending curvature, and ~70 nm for sensing the displacement.
PMID- 25121889
TI - Mid-infrared digital holography and holographic interferometry with a tunable
quantum cascade laser.
AB - Mid-infrared digital holography based on CO2 lasers has proven to be a powerful
coherent imaging technique due to reduced sensitivity to mechanical vibrations,
increased field of view, high optical power, and possible vision through
scattering media, e.g., smoke. Here we demonstrate a similar and more compact
holographic system based on an external cavity quantum cascade laser emitting at
8 MUm. Such a setup, which includes a highly sensitive microbolometric camera,
allows the acquisition of speckle holograms of scattering objects, which can be
processed in real time. In addition, by exploiting the broad laser tunability, we
can acquire holograms at different wavelengths, from which we extract phase
images not subjected to phase wrapping, at synthetic wavelengths ranging from
hundreds of micrometers to several millimeters.
PMID- 25121890
TI - Optical limiting properties of a nonlinear multilayer Fabry-Perot resonator
containing niobium pentoxide as nonlinear medium.
AB - The optical limiting effect was numerically simulated and experimentally observed
for a 25-layer thin-film Fabry-Perot microresonator by 7 ns laser pulses at 532
nm. The sample, made by vacuum evaporation and consisting of alternating Nb2O5
and SiO2 layers, has an ultranarrow line of transparency at near 532 nm within a
wide spectral band of reflection. By adjusting simulated results in accordance
with experimental dependencies of transmittance, reflectance, and absorbance on
incident light intensity, the coefficient of optical nonlinearity of Nb2O5 was
estimated at (6+1i).10(-12) cm2/W.
PMID- 25121891
TI - Combining cw-seeding with highly nonlinear fibers in a broadly tunable
femtosecond optical parametric amplifier at 42 MHz.
AB - We report on a precisely tunable and highly stable femtosecond oscillator-pumped
optical parametric amplifier at a 41.7 MHz repetition rate for spectroscopic
applications. A novel concept based on cw-seeding of a first amplification stage
with subsequent spectral broadening and shaping, followed by two further
amplification stages, allows for precise sub-nanometer and gap-free tuning from
1.35 to 1.75 MUm and 2.55 to 4.5 MUm. Excellent spectral stability is
demonstrated with deviations of less than 0.008% rms central wavelength and 1.6%
rms bandwidth over 1 h. Spectral shaping of the seed pulse allows precise
adjustment of both the bandwidth and the pulse duration over a broad range at a
given central wavelength. Transform-limited pulses nearly as short as 107 fs are
achieved. More than half a Watt of average power in the near- and more than 200
mW in the mid-infrared with power fluctuations less than 0.6% rms over 1 h
provide an excellent basis for spectroscopic experiments. The pulse-to-pulse
power fluctuations are as small as 1.8%. Further, we demonstrate for the first
time, to the best of our knowledge, that by using hollow-core capillaries with
highly nonlinear liquids as a host medium for self-phase modulation, the signal
tuning range can be extended and covers the region from 1.4 MUm up to the point
of degeneracy at 2.07 MUm. Hence, the idler covers 2.07 to 4.0 MUm.
PMID- 25121892
TI - High-power flip-chip semiconductor disk laser in the 1.3 MUm wavelength band.
AB - We present 6.1 W of output power from a flip-chip semiconductor disk laser (SDL)
emitting in the 1.3 MUm wavelength region. This is the first demonstration of a
flip-chip SDL in this wavelength range with output powers that are comparable to
those obtained with intracavity diamond heat spreaders. The flip-chip
configuration circumvents the optical distortions and losses that the intracavity
diamond heat spreaders can introduce into the laser cavity. This is essential for
several key applications of SDLs.
PMID- 25121894
TI - Cost-efficient delay generator for fast terahertz imaging.
AB - We present a fast and low-cost delay generator for terahertz (THz) waves that
transfers a rotational motion of a transparent dielectric cube into an effective
THz delay. The device is easily implemented in the THz beam path and allows for
coherent sampling over 40 ps with a scan rate of hundreds of hertz. Furthermore,
we show that our approach is particularly suitable for fast THz imaging.
PMID- 25121893
TI - Implications of Raman scattering and phase noise on multiple four-wave mixing
processes in an optical fiber.
AB - Implications of spontaneous and stimulated Raman scattering (SSRS) and phase
noise on the spatial evolution of multiple-order sidebands arising from four-wave
mixing (FWM) along the length of an optical fiber are investigated. A modified
split-step Fourier method is used to solve the governing coupled nonlinear
Schrodinger equations. The phase noise overcomes the depletive nature of SSRS and
stabilizes the FWM sidebands, in good agreement with experimental results.
PMID- 25121895
TI - Plasmonic routing in aperiodic graphene sheet arrays.
AB - We discover deep-subwavelength, low-loss, and diffraction-free surface plasmon
polariton (SPP) beam routing effects in aperiodic graphene sheet arrays (a-GSAs).
The a-GSAs are constructed by varying either the interlayer spaces between
graphene or the individual graphene chemical potentials. The SPP beams can be
accelerated or decelerated in the a-GSAs, resulting in beam routing in different
paths. The wave fronts of the beams are always parallel to the propagation
direction, allowing the generation of transverse radiation pressure. All of these
behaviors of SPPs are demonstrated by fully vectorial simulation and Hamilton
optics analysis.
PMID- 25121896
TI - Miniature forward-viewing spectrally encoded endoscopic probe.
AB - Spectrally encoded endoscopy is a promising technique for minimally invasive
imaging, allowing high-quality imaging through small diameter probes that do not
require rapid mechanical scanning. A novel optical configuration that employs
broadband visible light and dual-channel imaging is used to demonstrate a
miniature forward-viewing probe having a high number of resolvable points, low
speckle contrast, negligible backreflections, and high signal-to-noise ratio. The
system would be most suitable for imaging through narrow ducts and vessels for
clinical diagnosis at hard-to-reach locations in the body.
PMID- 25121897
TI - Remote wind sensing with a CW diode laser lidar beyond the coherence regime.
AB - We experimentally demonstrate for the first time (to our knowledge) a coherent CW
lidar system capable of wind speed measurement at a probing distance beyond the
coherence regime of the light source. A side-by-side wind measurement was
conducted on the field using two lidar systems with identical optical designs but
different laser linewidths. While one system was operating within the coherence
regime, the other was measuring at least 2.4 times the coherence range. The
probing distance of both lidars is 85 m and the radial wind speed correlation was
measured to be r2=0.965 between the two lidars at a sampling rate of 2 Hz. Based
on our experimental results, we describe a practical guideline for designing a
wind lidar operating beyond the coherence regime.
PMID- 25121898
TI - Fingerprints of topological defects in a metasurface.
AB - Singularity, representing a structurally stable topological defect (TD), plays a
pivotal role in various physical systems. Here we theoretically present the
fingerprints of TDs and uncover the resulting exotic optical properties in a
tailored metasurface system. The presence of the TDs results in coherent perfect
absorption, and dramatic optical property transition from slow to superluminal
light behavior when the parameters cross the TD. Our investigation provides a new
route to explore many phenomena of the TDs, extends the capabilities of
metasurface, and offers benefits to develop potential nanophotonic applications
based on the design of the metasurface.
PMID- 25121899
TI - Giant optical forces in planar dielectric photonic metamaterials.
AB - We demonstrate that resonant optical forces generated within all-dielectric
planar photonic metamaterials at near-infrared illumination wavelengths can be an
order of magnitude larger than in corresponding plasmonic metamaterials, reaching
levels many tens of times greater than the force resulting from radiation
pressure. This is made possible by the dielectric structures' freedom from Joule
losses and the consequent ability to sustain Fano-resonances with high quality
factors that are unachievable in plasmonic nanostructures. Dielectric nano
optomechanical metamaterials can thus provide a functional platform for a range
of novel dynamically controlled and self-adaptive nonlinear, tunable/switchable
photonic metamaterials.
PMID- 25121900
TI - Narsarsukite-structure fluorosilicate as a blue component for white LEDs:
structural and optical properties.
AB - A new blue-emitting phosphor, K2ScSi4O10F:Eu>2+ (KSSOF:Eu2+), was synthesized
through a solid-state reaction. The structural and optical properties of
KSSOF:Eu2+ phosphor, in addition to its thermal quenching and fabrication of
white LEDs (WLEDs), were investigated for the first time. The phosphor showed
broad blue emission, with a maximum at ~434 nm under near-ultraviolet excitation
due to 5d->4f transition of the Eu2+ ion. The critical distance was calculated to
be 12 A using the critical concentration of Eu2+ and Dexter's theory for energy
transfer. WLEDs were fabricated by blending KSSOF:Eu2+, commercial
Lu3Al5O12:Ce3+, and (Sr,Ca)AlSiN3:Eu2+ phosphors, showed a high color rendering
index of 88 at a correlated color temperature of 4134 K under a forward bias
current of 100 mA.
PMID- 25121901
TI - Extended parametric gain range in photonic crystal fibers with strongly frequency
dependent field distributions.
AB - The parametric gain range of a degenerate four-wave mixing process is determined
in the undepleted pump regime. The gain range is considered with and without
taking the mode field distributions of the four-wave mixing components into
account. It is found that the mode field distributions have to be included to
evaluate the parametric gain correctly in dispersion-tailored speciality fibers
and that mode profile engineering can provide a way to increase the parametric
gain range.
PMID- 25121902
TI - Narrow bandwidth, picosecond, 1064 nm pumped optical parametric generator for
the mid-IR based on HgGa2S4.
AB - We report on optical parametric generation in a mercury thiogallate (HgGa2S4)
crystal pumped by 16 ps, 1064 nm pulses at 250 kHz. A broad tuning range
extending from 1.19 to 1.47 MUm (signal) and from 3.85 to 10 MUm (idler) is
achieved. Narrow bandwidth, quasi-Fourier limited operation with high beam
quality for the signal/idler pulses and >14% pump depletion is obtained by
continuous wave seed injection at 1.29 MUm.
PMID- 25121903
TI - Bilayer holey plasmonic vortex lenses for the far field transmission of pure
orbital angular momentum light states.
AB - We report the design of a holey plasmonic vortex lens (PVL) structure able to
couple circularly polarized impinging light to a plasmonic vortex in the form of
the fundamental TM mode of a metal-insulator-metal plasmonic waveguide. The field
transmitted through the hole milled at the center of the second metal layer of
the structure is characterized by a well-defined spiral harmonic, entirely
determined by the spin of impinging light and by the chirality of the PVL
structure. Scattering finite elements simulations are presented for single layer
standard PVLs and for bilayer ones, comparing the spiral spectra of the
transmitted field and the efficiencies of the architectures.
PMID- 25121904
TI - Noncontact photoacoustic imaging based on all-fiber heterodyne interferometer.
AB - We report on a noncontact photoacoustic imaging system utilizing an all-fiber
optic heterodyne interferometer as an acoustic wave detector. The acoustic wave
generated by a short laser pulse via the photoacoustic effect and arriving at the
sample surface could be detected with the fiber-optic heterodyne interferometer
without physical contact or using an impedance matching medium. A phantom
experiment was conducted to evaluate the proposed system, and the initial
acoustic pressure distribution was calculated using a Fourier-based
reconstruction algorithm. It is expected that the all-fiber-optic configuration
of the proposed system can be applied as a minimally invasive diagnostic tool.
PMID- 25121905
TI - Phase conjugation of vector fields by degenerate four-wave mixing in a Fe-doped
LiNbO3.
AB - We propose a method to generate the phase-conjugate wave of the vector field by
degenerate four-wave mixing in a c-cut Fe-doped LiNbO3 crystal. We demonstrate
experimentally that the phase-conjugate wave of the vector field can be
generated. In particular, the phase-conjugate vector field has also the peculiar
function of compensating the polarization distortion, as the traditional phase
conjugate scaler field can compensate the phase distortion.
PMID- 25121906
TI - Design of spatio-temporally modulated static infrared imaging Fourier transform
spectrometer.
AB - A novel static medium wave infrared (MWIR) imaging Fourier transform spectrometer
(IFTS) is conceptually proposed and experimentally demonstrated. In this system,
the moving mirror in traditional temporally modulated IFTS is replaced by multi
step micro-mirrors to realize the static design. Compared with the traditional
spatially modulated IFTS, they have no slit system and are superior with larger
luminous flux and higher energy efficiency. The use of the multi-step micro
mirrors can also make the system compact and light.
PMID- 25121907
TI - Demonstration of tunable optical generation of higher-order modulation formats
using nonlinearities and coherent frequency comb.
AB - We demonstrate a tunable, optical generation scheme of higher-order modulation
formats including pulse amplitude modulation (PAM) and quadrature amplitude
modulation (QAM). Using this method, 100.4 Gbit/s 16-QAM and 120 Gbit/s 64-QAM
were generated from 50.2 and 40 Gbit/s QPSK signals at EVMs of 7.8% and 6.4%, and
60 Gbit/s 8-PAM were generated at an EVM of 8.1% using three 20-Gbit/s BPSK
signals. We also demonstrated a successful transmission of 80 Gbit/s 16-QAM
through 80 km SMF-28 after compensating with 20 km DCF. All signals were
generated, transmitted, and detected with BER below the forward error correction
threshold.
PMID- 25121908
TI - Suppression of nonlinear phonon relaxation in Yb:YAG thin disk via zero phonon
line pumping.
AB - A quantitative comparison of conventional absorption line (940 nm) pumping and
zero phonon line (ZPL) (969 nm) pumping of a Yb:YAG thin disk laser is reported.
Characteristics of an output beam profile, surface temperature, and deformation
of a thin disk under the different pump wavelengths are evaluated. We found that
a nonlinear phonon relaxation (NPR) of the excited state in Yb:YAG, which induces
nonlinear temperature rise and large aspheric deformation, did not appear in the
case of a ZPL pumped Yb:YAG thin disk. This means that the advantage of ZPL
pumping is not only the reduction of quantum defect but also the suppression of
NPR. The latter effect is more important for high power lasers.
PMID- 25121909
TI - Precise frequency measurement and characterization of a continuous scanning
single-mode laser with an optical frequency comb.
AB - We developed a high-precision frequency-measurement system for continuously
scanning single-mode cw lasers. The high precision for wide frequency range is
realized by employing an optical frequency comb. The developed system operates as
a strong tool for analyzing the spectral profile and scan characteristics of
lasers, which is suitable for high-resolution molecular spectroscopy. We
demonstrated the ability of our system with Doppler-free spectroscopy of
molecular iodine.
PMID- 25121910
TI - Using shadows to measure spatial coherence.
AB - We present a very simple method for measuring the spatial coherence of quasi
monochromatic fields through the comparison of two measurements of the radiant
intensity with and without a small obscuration at the test plane. From these
measurements one can measure simultaneously the field's coherence at all pairs of
points whose centroid is the centroid of the obstacle. This method can be
implemented without the need of any refractive or diffractive focusing elements.
PMID- 25121911
TI - Experimental observation of lateral emission in freestanding GaN-based membrane
devices.
AB - This Letter describes a double-sided process to fabricate freestanding membrane
devices on a GaN-on-silicon platform. The photoluminescence measurement is taken
to characterize the optical performance. A large portion of the excited light
from InGaN/GaN multiple quantum wells is trapped as waveguide modes and
propagates in different directions. Experimental results show that the
propagation direction of the waveguide mode can be converted into the direction
normal to the surface at the edge of a freestanding membrane, and the emitted
light is attenuated due to light propagation loss before it gets out from the
edge. Subwavelength grating can also convert waveguide modes into air modes on a
freestanding membrane. These results suggest that the emission efficiency can be
greatly improved by employing more efficient light extraction methods and that
GaN-based photonic waveguides are promising in the visible range.
PMID- 25121912
TI - One-way optical transmission in silicon grating-photonic crystal structures.
AB - One-way optical transmission through a composite structure of grating-photonic
crystal (PC) is presented. This unidirectional transportation property originates
from the diffraction of grating to change the direction of light incident into
the PC from pseudobandgaps to passbands of the PC. Numerical simulation shows
that a light beam in a certain range of frequencies can transmit the composite
structure when it is incident from the grating interface but is completely
reflected by the structure when it is incident from the PC interface, which is
further verified experimentally. The present structure may provide another more
compact way for designing on-chip optical diode-like integrated devices.
PMID- 25121913
TI - All-optical modulation and switching by a metamaterial of plasmonic circuits.
AB - We demonstrate experimentally the modulation and switching of one light beam by a
second beam using metamaterials constructed from arrays of plasmonic circuits.
Each circuit consists of three gold nanorods that mix together two coherent but
orthogonally polarized light beams leading to modulation by an interference
effect. By adjusting the phase and the amplitude of one of the beams, the
amplitude and spectral composition of the second beam is altered. The plasmonic
circuits display an asymmetry that enables an angle-dependent modulation, which
we demonstrate with a diffraction grating where the energy directed into two
diffraction orders is controlled by a second light beam. This effect appears like
an optically controlled blaze that we use to switch a light beam between two
different directions.
PMID- 25121914
TI - Single-mode air-clad liquid-core waveguides on a surface energy patterned
substrate.
AB - We demonstrate a new kind of single-mode micro-optical waveguide based on a
liquid core on top of solid substrate and air cladding. The liquid is held in
place by surface tension and patterned surface energy on the substrate. Due to
the smooth nature of the liquid/air interface down to the molecular level, low
scattering losses are expected. Losses were measured to be -6.0 and -7.8 dB/cm
for, respectively, 12 and 9 MUm wide waveguides.
PMID- 25121915
TI - Narrow-linewidth quantum cascade laser at 8.6 MUm.
AB - We report on a narrow-linewidth distributed-feedback quantum cascade laser at 8.6
MUm that is optical-feedback locked to a high-finesse V-shaped cavity. The
spectral purity of the quantum cascade laser is fully characterized using a high
sensitivity optical frequency discriminator, leading to a 1 ms linewidth of less
than 4 kHz and a minimum laser frequency noise spectral density as low as 0.01
Hz2/Hz for Fourier frequencies larger than 100 kHz. The cumulative standard
deviation of the laser intensity is better than 0.1% over an integration
bandwidth from 2 Hz to 100 MHz.
PMID- 25121917
TI - Tunable electro-optic filter based on metal-ferroelectric nanocomposite for VLC.
AB - The emerging technology of visible light communications (VLC) will provide a new
modality of communication. This technology uses illumination lighting to carry
information. We propose to add a smart capability to mitigate interferences from
unwanted light sources. This is achieved by adaptively filtering interference
light using a tunable filter to block interferences dynamically. In this Letter,
we present an innovative concept for a tunable notch filter based on
ferroelectric thin films embedded with noble metal nanoparticles. The adaptivity
of the filter is achieved by controlling the external applied voltage. This
voltage creates an electric field that changes the refractive index of the host
film through the linear electro-optic effect. Moreover, the fundamental
characteristics of the filter are determined by the layer's parameters, such as
film thickness, nanoparticles concentration and geometry, and the material of
both the host thin film and nanoparticles. We study the tunability of lead
zirconate titanate (PZT) embedded with Ag nanoparticles that reaches
approximately 50 nm, between 530 and 590 nm. Moreover, we showed that a PZT notch
filter embedded with Ag nanoshells has its stop band shifted to shorter
wavelengths. These tunable filters can be used as mode selectors inside a laser
resonator, spatial light filters for imaging and communication both for VLC and
infrared communication.
PMID- 25121916
TI - Generation of attenuation-compensating Airy beams.
AB - We present an attenuation-corrected "nondiffracting" Airy beam. The correction
factor can be adjusted to deliver a beam that exhibits an adjustable exponential
intensity increase or decrease over a finite distance. A digital micromirror
device that shapes both amplitude and phase is used to experimentally verify the
propagation of these beams through air and partially absorbing media.
PMID- 25121918
TI - Controlling high-power autofocusing waves with periodic lattices.
AB - We show numerically that by using radial symmetric lattices, the focal spot
characteristics and filament peak intensity of high-power autofocusing waves can
be controlled. The lattice induced diffraction is able to isolate the main on
axis peak and control the focus position. In addition, at higher power the
lattice can control and stabilize the peak intensity of the filament over an
extended distance.
PMID- 25121919
TI - Efficient excitation of photoluminescence in a two-dimensional waveguide
consisting of a quantum dot-polymer sandwich-type structure.
AB - In this Letter, we study a new kind of organic polymer waveguide numerically and
experimentally by combining an ultrathin (10-50 nm) layer of compactly packed
CdSe/ZnS core/shell colloidal quantum dots (QDs) sandwiched between two cladding
poly(methyl methacrylate) (PMMA) layers. When a pumping laser beam is coupled
into the waveguide edge, light is mostly confined around the QD layer, improving
the efficiency of excitation. Moreover, the absence of losses in the claddings
allows the propagation of the pumping laser beam along the entire waveguide
length; hence, a high-intensity photoluminescence (PL) is produced. Furthermore,
a novel fabrication technology is developed to pattern the PMMA into ridge
structures by UV lithography in order to provide additional light confinement.
The sandwich-type waveguide is analyzed in comparison to a similar one formed by
a PMMA film homogeneously doped by the same QDs. A 100-fold enhancement in the
waveguided PL is found for the sandwich-type case due to the higher concentration
of QDs inside the waveguide.
PMID- 25121920
TI - Experimental observation of the effect of generic singularities in polychromatic
dark hollow beams.
AB - This Letter presents the essence of our recent experimental study on generic
singularities carrying spatially partially coherent, polychromatic dark hollow
beams (PDHBs). To the best of our knowledge, this is the first experimental
demonstration of generic singularities-induced wavefront tearing in focused
polychromatic beams.
PMID- 25121921
TI - Polarization-diversified photonic comb filter with independently tunable free
spectrum range.
AB - A polarization-diversified photonic comb filter with tunable free spectrum range
(FSR) is proposed using two variable differential group delay (DGD) elements in a
loop configuration. Two different cosine transfer functions could be
simultaneously realized on orthogonal polarization states. Experimental
demonstrations also verify feasibilities in various reconfigurable transfer
functions.
PMID- 25121922
TI - Cascaded uncoupled dual-ring modulator.
AB - We demonstrate, by coherent driving two uncoupled rings in same direction, that
the effective photon circulating time in the dual-ring modulator is reduced, with
increased modulation quality. The inter-ring detuning-dependent photon dynamics,
Q factor, extinction ratio, and optical modulation amplitude of two cascaded
silicon ring resonators are studied and compared with that of a single-ring
modulator. Experimentally measured eye diagrams, together with coupled mode
theory simulations, demonstrate the enhancement of the dual-ring configuration at
20 Gbps with a Q~20,000.
PMID- 25121924
TI - Protein stable isotope fingerprinting: multidimensional protein chromatography
coupled to stable isotope-ratio mass spectrometry.
AB - Protein stable isotope fingerprinting (P-SIF) is a method to measure the carbon
isotope ratios of whole proteins separated from complex mixtures, including
cultures and environmental samples. The goal of P-SIF is to expose the links
between taxonomic identity and metabolic function in microbial ecosystems. To
accomplish this, two dimensions of chromatography are used in sequence to resolve
a sample containing ca. 5-10 mg of mixed proteins into 960 fractions. Each
fraction then is split in two aliquots: The first is digested with trypsin for
peptide sequencing, while the second has its ratio of (13)C/(12)C (value of
delta(13)C) measured in triplicate using an isotope-ratio mass spectrometer
interfaced with a spooling wire microcombustion device. Data from cultured
species show that bacteria have a narrow distribution of protein delta(13)C
values within individual taxa (+/-0.7-1.20/00, 1sigma). This is moderately larger
than the mean precision of the triplicate isotope measurements (+/-0.50/00,
1sigma) and may reflect heterogeneous distribution of (13)C among the amino
acids. When cells from different species are mixed together prior to protein
extraction and separation, the results can predict accurately (to within +/
1sigma) the delta(13)C values of the original taxa. The number of data points
required for this endmember prediction is >=20/taxon, yielding a theoretical
resolution of ca. 10 taxonomic units/sample. Such resolution should be useful to
determine the overall trophic breadth of mixed microbial ecosystems. Although we
utilize P-SIF to measure natural isotope ratios, it also could be combined with
experiments that incorporate stable isotope labeling.
PMID- 25121925
TI - Concentration dependence of ionic hydration numbers.
AB - Isothermal compressibility data of 23 aqueous electrolyte solutions at 25
degrees C from the literature are used to calculate their hydration numbers,
which diminish as the concentration increases. Their limit at very high
concentration is near the "number of adsorption sites" of water molecules on the
ions, obtained by the BET method. On the contrary, hydration numbers obtained
from ultrasound speed measurements yielding isentropic compressibilities cannot
be valid, being much too large at infinite dilution.
PMID- 25121923
TI - Wage, work environment, and staffing: effects on nurse outcomes.
AB - Research has shown that hospitals with better nurse staffing and work
environments have better nurse outcomes-less burnout, job dissatisfaction, and
intention to leave the job. Many studies, however, have not accounted for wage
effects, which may confound findings. By using a secondary analysis with cross
sectional administrative data and a four-state survey of nurses, we investigated
how wage, work environment, and staffing were associated with nurse outcomes.
Logistic regression models, with and without wage, were used to estimate the
effects of work environment and staffing on burnout, job dissatisfaction, and
intent to leave. We discovered that wage was associated with job dissatisfaction
and intent to leave but had little influence on burnout, while work environment
and average patient-to-nurse ratio still have considerable effects on nurse
outcomes. Wage is important for good nurse outcomes, but it does not diminish the
significant influence of work environment and staffing on nurse outcomes.
PMID- 25121927
TI - Incidence of steroid-induced ocular hypertension after vitreoretinal surgery with
difluprednate versus prednisolone acetate.
AB - PURPOSE: To identify changes in intraocular pressure (IOP) after vitreoretinal
surgical procedures in eyes that received either difluprednate ophthalmic
emulsion 0.05% (DP) or prednisolone acetate ophthalmic suspension 1% (PA).
METHODS: A retrospective chart review compared a consecutive series of 100
patients who received DP with 100 patients who received PA after vitreoretinal
surgery. Data were collected for a 3-month period from the time of surgery.
RESULTS: A significantly higher number of patients treated with DP (35%, n = 35)
developed increased IOP (>21 mmHg with a change from baseline of >10 mmHg)
compared with those receiving PA (22%, n = 22) (P = 0.042). The mean maximum IOP
in the DP cohort (26.7 mmHg) was significantly higher than that in the PA cohort
(22.8 mmHg) (P = 0.0027). Additionally, the rise in IOP from baseline was
significantly higher in the DP-treated cohort (9.0 mmHg) than that in the PA
treated cohort (6.0 mmHg) (P = 0.027). CONCLUSION: Eyes treated with DP after
vitreoretinal surgery were at increased risk for developing clinically
significant increases in IOP compared with those receiving PA.
PMID- 25121928
TI - Visual and anatomical outcomes of macular epiretinal membrane peeling after
previous rhegmatogenous retinal detachment repair.
AB - PURPOSE: To report outcomes and prognostic factors after epiretinal membrane
peeling in patients with previous rhegmatogenous retinal detachment repair.
METHODS: A consecutive case series. Best-corrected visual acuity and optical
coherence tomography characteristics were analyzed before and after epiretinal
membrane surgery. RESULTS: Fifty-three eyes were analyzed. Best-corrected visual
acuity improved by a mean of 10 letters at 1 month (N = 45; P = 0.001), 15 at 3
months (N = 42; P < 0.001), 11 at 6 months (N = 35; P = 0.001), and 16 at 12
months (N = 33; P < 0.001). The mean optical coherence tomography central foveal
thickness decreased by 141 (N = 22; P < 0.001), 185 (N = 24; P < 0.001), 180 (N =
17; P = 0.001), and 151 MUm (N = 9; P = 0.017) at 1, 3, 6, and 12 months,
respectively. Better preoperative best-corrected visual acuity correlated with
better best-corrected visual acuity at all follow-up visits (P <= 0.001). Intact
preoperative inner segment/outer segment junction and external limiting membrane
line, but not the change in central foveal thickness or location of fluid,
correlated with better postoperative best-corrected visual acuity through 6
months. CONCLUSION: Epiretinal membrane peeling after previous rhegmatogenous
retinal detachment repair resulted in significant improvements in visual acuity
and optical coherence tomography thickness, even in eyes with previous macula
involving rhegmatogenous retinal detachment. Better preoperative visual acuity
and intact outer retinal layers by optical coherence tomography were the main
prognostic factors for visual outcomes.
PMID- 25121929
TI - Diagnostic and therapeutic challenges.
PMID- 25121926
TI - Cholesterol selectively regulates IL-5 induced mitogen activated protein kinase
signaling in human eosinophils.
AB - Eosinophils function contributes to human allergic and autoimmune diseases, many
of which currently lack curative treatment. Development of more effective
treatments for eosinophil-related diseases requires expanded understanding of
eosinophil signaling and biology. Cell signaling requires integration of
extracellular signals with intracellular responses, and is organized in part by
cholesterol rich membrane microdomains (CRMMs), commonly referred to as lipid
rafts. Formation of these organizational membrane domains is in turn dependent
upon the amount of available cholesterol, which can fluctuate widely with a
variety of disease states. We tested the hypothesis that manipulating membrane
cholesterol content in primary human peripheral blood eosinophils (PBEos) would
selectively alter signaling pathways that depend upon membrane-anchored signaling
proteins localized within CRMMs (e.g., mitogen activated protein kinase [MAPK]
pathway), while not affecting pathways that signal through soluble proteins, like
the Janus Kinase/Signal Transducer and Activator of Transcription [JAK/STAT]
pathway. Cholesterol levels were increased or decreased utilizing cholesterol
chelating methyl-beta-cyclodextrin (MbetaCD), which can either extract membrane
cholesterol or add exogenous membrane cholesterol depending on whether MbetaCD is
preloaded with cholesterol. Human PBEos were pretreated with MbetaCD (cholesterol
removal) or MbetaCD+Cholesterol (MbetaCD+Chol; cholesterol delivery); subsequent
IL-5-stimulated signaling and physiological endpoints were assessed. MbetaCD
reduced membrane cholesterol in PBEos, and attenuated an IL-5-stimulated p38 and
extracellular-regulated kinase 1/2 phosphorylation (p-p38, p-ERK1/2), and an IL-5
dependent increase in interleukin-1beta (IL-1beta) mRNA levels. In contrast,
MbetaCD+Chol treatment elevated PBEos membrane cholesterol levels and basal p
p38, but did not alter IL-5-stimulated phosphorylation of ERK1/2, STAT5, or
STAT3. Furthermore, MbetaCD+Chol pretreatment attenuated an IL-5-induced increase
in cell survival at 48 hours, measured as total cellular metabolism. The
reduction in cell survival following cholesterol addition despite unaltered STAT
phosphorylation contradicts the current dogma in which JAK/STAT activation is
sufficient to promote eosinophil survival, and suggests an additional,
unidentified mechanism critically regulates IL-5-mediated human PBEos survival.
PMID- 25121930
TI - Impact of duration of macula-off retinal detachment on visual outcome: a
systematic review and meta-analysis of literature.
AB - PURPOSE: To systematically review the influence of the lag time between macula
off retinal detachment and surgical intervention on postoperative visual acuity
as main outcome measure. METHODS: Systematic review and meta-analysis of articles
published from 1995 to October 2013 of patients with macula-off retinal
detachment and treated with scleral buckling or pars plana vitrectomy. Eligible
data were pooled in a meta-analysis, analyzing the odds ratio between different
durations of <= 3, <= 4, <= 7, and <= 10 days, comparing a final visual acuity of
<= 0.4 logMAR with >0.4 logMAR, using a random-effects model. Last, the number
needed to treat was calculated. RESULTS: Fourteen articles were eligible, of
which 9 studies contained data that were suitable for meta-analysis. Patients who
were operated with scleral buckling (n = 602) within 3 days since macular
detachment had a statistically significant better chance of reaching a final
visual acuity of 0.4 logMAR or better compared with a longer duration of macular
detachment, with an odds ratio for <= 3 days versus 4 days to 7 days of 2.86 (95%
confidence interval, 1.37-5.99) and an odds ratio for <= 3 days versus >3 days of
3.09 (95% confidence interval, 1.56-6.12), and with a number needed to treat of
4. For pars plana vitrectomy, the limited amount of data precluded a meta
analysis with substantial results. CONCLUSION: This meta-analysis suggests that
scleral buckling for macular detachment must preferably be performed within 3
days to optimize visual outcome.
PMID- 25121931
TI - Preoperative carbohydrate treatment for enhancing recovery after elective
surgery.
AB - BACKGROUND: Preoperative carbohydrate treatments have been widely adopted as part
of enhanced recovery after surgery (ERAS) or fast-track surgery protocols.
Although fast-track surgery protocols have been widely investigated and have been
shown to be associated with improved postoperative outcomes, some individual
constituents of these protocols, including preoperative carbohydrate treatment,
have not been subject to such robust analysis. OBJECTIVES: To assess the effects
of preoperative carbohydrate treatment, compared with placebo or preoperative
fasting, on postoperative recovery and insulin resistance in adult patients
undergoing elective surgery. SEARCH METHODS: We searched the Cochrane Central
Register of Controlled Trials (CENTRAL) (2014, Issue 3), MEDLINE (January 1946 to
March 2014), EMBASE (January 1947 to March 2014), the Cumulative Index to Nursing
and Allied Health Literature (CINAHL) (January 1980 to March 2014) and Web of
Science (January 1900 to March 2014) databases. We did not apply language
restrictions in the literature search. We searched reference lists of relevant
articles and contacted known authors in the field to identify unpublished data.
SELECTION CRITERIA: We included all randomized controlled trials of preoperative
carbohydrate treatment compared with placebo or traditional preoperative fasting
in adult study participants undergoing elective surgery. Treatment groups needed
to receive at least 45 g of carbohydrates within four hours before surgery or
anaesthesia start time. DATA COLLECTION AND ANALYSIS: Data were abstracted
independently by at least two review authors, with discrepancies resolved by
consensus. Data were abstracted and documented pro forma and were entered into
RevMan 5.2 for analysis. Quality assessment was performed independently by two
review authors according to the standard methodological procedures expected by
The Cochrane Collaboration. When available data were insufficient for quality
assessment or data analysis, trial authors were contacted to request needed
information. We collected trial data on complication rates and aspiration
pneumonitis. MAIN RESULTS: We included 27 trials involving 1976 participants
Trials were conducted in Europe, China, Brazil, Canada and New Zealand and
involved patients undergoing elective abdominal surgery (18), orthopaedic surgery
(4), cardiac surgery (4) and thyroidectomy (1). Twelve studies were limited to
participants with an American Society of Anaesthesiologists grade of I-II or I
III.A total of 17 trials contained at least one domain judged to be at high risk
of bias, and only two studies were judged to be at low risk of bias across all
domains. Of greatest concern was the risk of bias associated with inadequate
blinding, as most of the outcomes assessed by this review were subjective. Only
six trials were judged to be at low risk of bias because of blinding.In 19 trials
including 1351 participants, preoperative carbohydrate treatment was associated
with shortened length of hospital stay compared with placebo or fasting (by 0.30
days; 95% confidence interval (CI) 0.56 to 0.04; very low-quality evidence). No
significant effect on length of stay was noted when preoperative carbohydrate
treatment was compared with placebo (14 trials including 867 participants; mean
difference -0.13 days; 95% CI -0.38 to 0.12). Based on two trials including 86
participants, preoperative carbohydrate treatment was also associated with
shortened time to passage of flatus when compared with placebo or fasting (by
0.39 days; 95% CI 0.70 to 0.07), as well as increased postoperative peripheral
insulin sensitivity (three trials including 41 participants; mean increase in
glucose infusion rate measured by hyperinsulinaemic euglycaemic clamp of 0.76
mg/kg/min; 95% CI 0.24 to 1.29; high-quality evidence).As reported by 14 trials
involving 913 participants, preoperative carbohydrate treatment was not
associated with an increase or a decrease in the risk of postoperative
complications compared with placebo or fasting (risk ratio of complications 0.98,
95% CI 0.86 to 1.11; low-quality evidence). Aspiration pneumonitis was not
reported in any patients, regardless of treatment group allocation. AUTHORS'
CONCLUSIONS: Preoperative carbohydrate treatment was associated with a small
reduction in length of hospital stay when compared with placebo or fasting in
adult patients undergoing elective surgery. It was found that preoperative
carbohydrate treatment did not increase or decrease postoperative complication
rates when compared with placebo or fasting. Lack of adequate blinding in many
studies may have contributed to observed treatment effects for these subjective
outcomes, which are subject to possible biases.
PMID- 25121933
TI - Registered nurses, nurse specialists and physicians have a neutral to moderately
positive view on nurse prescribing, though physicians still have patient safety
concerns.
AB - Implications for practice and research: The process of assigning medical roles to
nurses has to be gradual and stepwise. The influence of this process on the
consequences for the nursing and medical professions, and for the quality of
care, should be investigated further.
PMID- 25121934
TI - Nurse home visits for infants and toddlers of low-income families improve
behavioural, language and attention outcomes at age 6-9 years; paraprofessional
visits improve visual attention and task switching.
AB - Implications for practice and research: Infant home visiting can be efficacious
in improving child developmental outcomes throughout early childhood. Home
visiting by trained nurses produce positive outcomes, whereas outcomes for
paraprofessionals are mixed. This study suggests that future research should be
directed towards understanding how nurses have a more positive impact on mothers
and their children than paraprofessionals.
PMID- 25121935
TI - Health professionals' pain management decisions are influenced by their role
(nurse or physician) and by patient gender, age and ethnicity.
AB - Implications for practice and research: Healthcare providers from different
fields may respond differently to patients with pain. On average, nurses rated
pain intensity higher than physicians and were more likely to prescribe opioids.
Patient demographic characteristics may influence nurses' and physicians'
perceptions of pain intensity and decisions to treat pain with opioid analgesics.
This study must be replicated with a more robust study design before findings can
be translated into recommendations for intervention.
PMID- 25121936
TI - High prevalence of neck, shoulder and back pain among nursing graduates warrants
preventive strategies during the degree and into working life.
AB - Implications for practice and research: Physical, organisational and social
aspects of work significantly contribute to musculoskeletal pain in nurses, along
with nonoccupational contextual and personal factors. Measures to prevent neck,
shoulder and back pain in nurses should be implemented for nurses from the very
beginning of their training programmes, while modifications to overtime work and
physical loads should be seriously considered. Preventive measures targeting
overtime work, physical workload and psychosocial factors need investigating
further.
PMID- 25121937
TI - Magnetic reflectometry of heterostructures.
AB - Measuring the magnetic configuration at complex buried layers and interfaces is
an important task, which requires especially a non-destructive probing technique.
X-ray resonant magnetic reflectometry (XRMR) combines the non-destructive depth
profiling potential of x-ray reflectometry with the excellent sensitivity for
magnetic phenomena, utilizing the x-ray magnetic circular dichroism effect. It
provides the magnetic spatial distribution with a precision down to the angstrom
scale, combined with element and symmetry specificity, sub-monolayer sensitivity,
and the possible separation of spin and orbital magnetic moments. This review
provides an overview to the XRMR technique in a tutorial way. We focus on the
introduction to the theory, measurement types, and data simulation. We provide
related experimental examples and show selected applications.
PMID- 25121932
TI - Conditional inactivation of Upstream Binding Factor reveals its epigenetic
functions and the existence of a somatic nucleolar precursor body.
AB - Upstream Binding Factor (UBF) is a unique multi-HMGB-box protein first identified
as a co-factor in RNA polymerase I (RPI/PolI) transcription. However, its poor
DNA sequence selectivity and its ability to generate nucleosome-like
nucleoprotein complexes suggest a more generalized role in chromatin structure.
We previously showed that extensive depletion of UBF reduced the number of
actively transcribed ribosomal RNA (rRNA) genes, but had little effect on rRNA
synthesis rates or cell proliferation, leaving open the question of its
requirement for RPI transcription. Using gene deletion in mouse, we now show that
UBF is essential for embryo development beyond morula. Conditional deletion in
cell cultures reveals that UBF is also essential for transcription of the rRNA
genes and that it defines the active chromatin conformation of both gene and
enhancer sequences. Loss of UBF prevents formation of the SL1/TIF1B pre
initiation complex and recruitment of the RPI-Rrn3/TIF1A complex. It is also
accompanied by recruitment of H3K9me3, canonical histone H1 and HP1alpha, but not
by de novo DNA methylation. Further, genes retain penta-acetyl H4 and H2A.Z,
suggesting that even in the absence of UBF the rRNA genes can maintain a
potentially active state. In contrast to canonical histone H1, binding of H1.4 is
dependent on UBF, strongly suggesting that it plays a positive role in gene
activity. Unexpectedly, arrest of rRNA synthesis does not suppress transcription
of the 5S, tRNA or snRNA genes, nor expression of the several hundred mRNA genes
implicated in ribosome biogenesis. Thus, rRNA gene activity does not coordinate
global gene expression for ribosome biogenesis. Loss of UBF also unexpectedly
induced the formation in cells of a large sub-nuclear structure resembling the
nucleolar precursor body (NPB) of oocytes and early embryos. These somatic NPBs
contain rRNA synthesis and processing factors but do not associate with the rRNA
gene loci (NORs).
PMID- 25121938
TI - Objective evaluation of elbow flexion strength and fatigability after nerve
transfer in adult traumatic upper brachial plexus injuries.
AB - Nerve transfers Oberlin-type are currently used in upper brachial plexus lesions
to recover elbow flexion. Is the regained active motion sufficient to resume
heavy manual activities? Five adult patients (mean age 37 years) operated of a
nerve transfer to recover elbow flexion (transfer of a motor fascicle of the
ulnar nerve to the motor branch of the biceps; in three patients, additional
transfer from the median to the motor nerve of the brachialis) were clinically
and isokinetically evaluated, after a mean follow-up of 47 months. The median
Constant-Murley score was 22/100, the DASH 56/100 and the MEPI 60/100. For
isokinetic tests the most significant finding was a severe deficit of elbow
strength, of about 80%. No patient was able to maintain an isometric contraction
during sufficient time to evaluate fatigability. This preliminary study suggests
that major functional impairments persist despite early recovery of elbow
flexion. These results should be confirmed in a study on a larger group of
patients.
PMID- 25121939
TI - Coronal fracture of the scaphoid--a case report and literature review.
AB - Coronal fracture of the scaphoid is a rare configuration of scaphoid fracture.
Only three cases have been found to be reported in English literature. In our
case, a 25-year-old man sustained right wrist injury after a fall with an
outstretched hand, was suspected of suffering from a scaphoid fracture as shown
on the pre-operative plain radiograph. Coronal fracture of the patient's scaphoid
was found intra-operatively and was fixed with two headless compression screws in
dorsal-to-volar direction. Post-operative outcome was clinically good as patient
was symptom-free, and a computed tomography and radiograph showed complete
healing of the fracture with no sign of avascular necrosis.
PMID- 25121940
TI - Wrist rhythm during wrist joint motion evaluated by dynamic radiography.
AB - We hypothesized that wrist joint motion involves a "wrist rhythm" similar to the
scapulohumeral rhythm. Therefore, we used a flat-panel detector to evaluate the
ratio of radiolunate and capitolunate joint motions during wrist joint motion by
dynamic radiography. The subjects were 20 healthy men. Dynamic imaging of the
wrist joint was performed during active exercise for a total of ten seconds. In
this study, we defined the radiocarpal (RL angle) and midcarpal joint angle (CL
angle) as the wrist joint angle in the obtained images and measured the variation
of these angles. The average curve was plotted and regression lines calculated
from the average curve. The ratio was calculated from the slopes of the
regression lines of the RL CL angles. These findings indicated that the ratio of
the RL and CL angle motions was approximately 1:4 during palmar flexion and
approximately 2:1 during dorsiflexion.
PMID- 25121941
TI - Bilateral bipartite carpal scaphoid: a case report and literature review.
AB - Congenital bipartite carpal scaphoid has been reported as an extremely rare
congenital anomaly. We report a case of a 47-year-old man who was found with
bilateral bipartite carpal scaphoids with no history of injury. Radiographs
demonstrated symmetric findings of the distinct bipartition of the scaphoid
without obvious degenerative change in both wrists. The patient complained of no
other symptoms. The diagnostic differentiation of scaphoid bipartition from the
pseudarthrosis of the scaphoid could be important in avoiding unnecessary surgery
and inappropriate assessment in compensation cases.
PMID- 25121942
TI - Modified Brunelli pull-out suture technique in zone II flexor tendon rupture: a
fresh human cadaver study.
AB - PURPOSE: The aim of our study is to develop a suture technique that has
sufficient strength of active mobilization. METHODS: Thirty two fingers of six
fresh human cadavers were divided into two groups. Flexor digitorum profundus
(FDP) tendons in the study group were repaired by modified Brunelli suture
technique and modified Kessler suture technique, while those in the control group
were repaired by Modified Kessler suture technique. Flexion and extension
movements were performed with 10 N of load, increasing 1 N at a time to the
tendons in both groups. Rupture and significant gap formation was evaluated up to
20 N of load. In the study, to evaluate the resistance to active motion, 1000
times flexion and extension motion cycle was performed with a load of 20 N. The
succeeding repaired tendons was also tested with flexion and extension movements
increasing the load 1 N at a time. RESULTS: In the study group, failure and
significant gap formation on the repair zone were not observed after 20 N of load
and 1000 times cyclic flexion and extension movements for resisting to active
motion. The rupture and significant gap formation was observed on a average load
of 98.43 +/- 0.47 N. In the Modified Kessler suture technique, on the eight
tendons before reaching the 20 N of load for resisting to active motion, and the
remaining eight tendons, during the 20 N loaded motion cycle essential for active
motion, rupture and significant gap formation was observed. The failure and
significant gap formation was observed on a average load of 18.37 +/- 1.89 N. It
is measured that by accompanying Modified Brunelli suture to the Modified Kessler
suture technique, the resistance was increased up to 5-6 times. DISCUSSION: By
the Modified Brunelli suture technique, active motion can be started to the
finger without a dorsal block sling immediately after the surgery. Clinical
Relavans: By the modified technique, the rehabilitation difficulty and joint
stiffness will be minimized.
PMID- 25121943
TI - Locking finger due to a partial laceration of the flexor digitorum superficialis
tendon: a case report.
AB - A 39-year-old woman sustained a small wound on the palm of her right hand, which
quickly healed naturally; however, a month later pain and limited range of motion
were noted in her right finger. Surgery revealed the radial half of the flexor
digitorum superficialis (FDS) tendon was ruptured and formed a flap, which hooked
at the entrance of the A1 pulley. The proximal stump was sutured to the remaining
ulnar (normal) side of the FDS tendon. Locking occurs between the tendon flap and
the tendon sheath; therefore, when there is no fibrous tendon sheath near the
partially ruptured tendon, locking will not occur.
PMID- 25121944
TI - Volar perilunate trans-scaphoid dislocation: a case.
AB - We report a rare case of volar perilunate trans-scaphoid dislocation that was
treated with open reduction and internal fixation.
PMID- 25121945
TI - Associations between ulnar nerve strain and accompanying conditions in patients
with cubital tunnel syndrome.
AB - Pathophysiology of cubital tunnel syndrome (CubTS) is still controversial. Ulnar
nerve strain at the elbow was measured intraoperatively in 13 patients with CubTS
before simple decompression. The patients were divided into three groups
according to their accompanying conditions: compression/adhesion, idiopathic, and
relaxation groups. The mean ulnar nerve strain was 43.5 +/- 30.0%, 25.5 +/-
14.8%, and 9.0 +/- 5.0% in the compression/adhesion, idiopathic, and relaxation
groups respectively. The mean ulnar nerve strains in patients with McGowan's
classification grades I, II, and III were 18.0 +/- 4.2%, 27.1 +/- 22.7%, and 33.7
+/- 24.7%, respectively. The Jonckheere-Terpstra test showed that there were
significant reductions in the ulnar nerve strain among the first three groups,
but not in the three groups according to McGowan's classification. Our results
suggest that the pathophysiology, not disease severity, of CubTS may be explained
at least in part by the presence of ulnar nerve strain.
PMID- 25121946
TI - Treatment of hook of the hamate fractures in adults using low-intensity pulsed
ultrasound.
AB - Two delayed unions and one nonunion of hook of the hamate fractures in adults
aged 31-, 40-, and 41-years-old were treated with low-intensity pulsed ultrasound
(LIPUS). Ultrasound treatment was started at three, four, and six months after
injury and ultrasound exposure at the hook of the hamate in the hypothenar
eminence was carried out for four to five months. During the management period,
there was no immobilisation with a cast or brace and limited strain with only
routine daily activities allowed. In all cases, bony union was confirmed on
carpal tunnel radiographs or computed tomography at the final follow-up time of
eight and 36 months after injuries.
PMID- 25121947
TI - Strain-specific properties and T cells regulate the susceptibility to papilloma
induction by Mus musculus papillomavirus 1.
AB - The immunocytes that regulate papillomavirus infection and lesion development in
humans and animals remain largely undefined. We found that immunocompetent mice
with varying H-2 haplotypes displayed asymptomatic skin infection that produced
L1 when challenged with 6*1010 MusPV1 virions, the recently identified domestic
mouse papillomavirus (also designated "MmuPV1"), but were uniformly resistant to
MusPV1-induced papillomatosis. Broad immunosuppression with cyclosporin A
resulted in variable induction of papillomas after experimental infection with a
similar dose, from robust in Cr:ORL SENCAR to none in C57BL/6 mice, with lesional
outgrowth correlating with early viral gene expression and partly with reported
strain-specific susceptibility to chemical carcinogens, but not with H-2
haplotype. Challenge with 1*1012 virions in the absence of immunosuppression
induced small transient papillomas in Cr:ORL SENCAR but not in C57BL/6 mice.
Antibody-induced depletion of CD3+ T cells permitted efficient virus replication
and papilloma formation in both strains, providing experimental proof for the
crucial role of T cells in controlling papillomavirus infection and associated
disease. In Cr:ORL SENCAR mice, immunodepletion of either CD4+ or CD8+ T cells
was sufficient for efficient infection and papillomatosis, although deletion of
one subset did not inhibit the recruitment of the other subset to the infected
epithelium. Thus, the functional cooperation of CD4+ and CD8+ T cells is required
to protect this strain. In contrast, C57BL/6 mice required depletion of both CD4+
and CD8+ T cells for infection and papillomatosis, and separate CD4 knock-out and
CD8 knock-out C57BL/6 were also resistant. Thus, in C57BL/6 mice, either CD4+ or
CD8+ T cell-independent mechanisms exist that can protect this particular strain
from MusPV1-associated disease. These findings may help to explain the diversity
of pathological outcomes in immunocompetent humans after infection with a
specific human papillomavirus genotype.
PMID- 25121948
TI - Predictive clinical indicators of biochemical progression in advanced prostate
cancer patients receiving Leuplin depot as androgen deprivation therapy.
AB - Therapeutic planning and counseling for advanced prostate cancer patients
receiving androgen deprivation therapy (ADT) is complicated because the prognoses
are highly variable. The purpose of this study is to identify predictive clinical
indicators of biochemical progression (BCP). In this retrospective analysis, data
from 107 newly diagnosed patients (from November 1995 to April 2008) with
advanced prostate adenocarcinoma receiving Leuprorelin acetate depot were
analyzed. Data was collected from the computerized registry of two collaborating
medical centers in Taiwan. Cox regression and Kaplan-Meier analyses were used to
evaluate the relationship between potential predictive parameters and BCP.
Univariate analysis revealed that predictors of BCP included (1) initial serum
prostate-specific antigen (PSA) (hazard ratio [HR], 1.00; 95% confidence interval
[CI] 1.00-1.00); (2) log of initial PSA (HR, 1.35; 95% CI 1.17-1.56); (3) PSA
density at diagnosis (HR, 1.00; 95% CI 1.00-1.01), and (4) pathological bone
fracture (HR, 2.22; 95% CI 1.20-4.11). Age (HR, 0.94; 95% CI 0.91-0.98) and
hemoglobin levels (HR, 0.86; 95% CI 0.76-0.97) were also associated with greater
risk of BCP. After adjusting for age, pathologic fracture, and hemoglobin level,
the initial PSA and PSA density were no longer significantly associated with BCP.
However, age and hemoglobin levels continued to be associated with greater risk
of BCP (P <= 0.007). Using Kaplan-Meier analysis, patients with higher initial
PSA concentration, pathological bone fracture, and low hemoglobin had a greater
probability of BCP. Thus, low hemoglobin and age are predictive indicators of BCP
and therefore early indicators of BCP despite ADT therapy.
PMID- 25121950
TI - CE: Champions for central line care.
AB - OVERVIEW: In 2012, acute care hospitals in the United States reported 30,100
central line-associated bloodstream infections (CLABSIs) to the National
Healthcare Safety Network of the Centers for Disease Control and Prevention.
Known to substantially increase morbidity, length of stay, and cost of care,
CLABSIs are associated with a mortality rate of 12% to 25% and an additional cost
of $22,885 to $29,330 per incident. Following five months with a sustained CLABSI
rate of zero per 1,000 catheter days, the acuity adaptable critical care unit at
Geisinger Medical Center in Danville, Pennsylvania, saw the CLABSI rate spike to
3.97 per 1,000 catheter days in March 2011, prompting a quality improvement
project and, ultimately, the implementation within the unit of a champion team
program to guide central line care.
PMID- 25121949
TI - CE: Original Research: Staff nurses' use of research to facilitate evidence-based
practice.
AB - OBJECTIVES: To determine to what extent RNs in an acute care multihospital system
used research findings in their practice; what types of knowledge they used in
their practice; and what personal, professional, and organizational factors
enhanced or hindered their research utilization. METHODS: A cross-sectional,
descriptive, online survey design was used. The survey, which asked about use of
research findings in practice and evidence-based practice (EBP) participation,
was placed on the hospital system intranet. Of the 2,900 RNs invited to
participate, 1,112 nurses completed usable surveys, for a response rate of 38%.
This article reports findings for 794 of the staff nurses who responded to the
survey. RESULTS: The forms of knowledge that staff nurses reported relying on
most were their personal experience with patients, conferences, hospital policies
and procedures, physician colleagues, and nursing peers. Although a variety of
resources were available for nurses to use in locating research and implementing
EBP, respondents reported many of the same barriers that have been reported in
other studies over the last two decades: lack of time, lack of resources, and
lack of knowledge. Although their attitudes about research utilization and EBP
were positive overall, respondents expected unit-based educators and clinical
nurse specialists to collect and synthesize the research for them. CONCLUSIONS:
These findings are similar to those of other recent studies regarding nurses'
research utilization and EBP. A great deal of work remains to be done if we are
to inform, educate, and assist staff nurses in using research and implementing
EBP. It may be unrealistic to expect bedside nurses to add these activities to
their duties unless they are compensated for the time and have the support of
master's or doctorally prepared nurses to serve as EBP coaches and champions.
PMID- 25121952
TI - Response to comment on 'Preoperative nomogram for the identification of lymph
node metastasis in early cervical cancer'.
PMID- 25121951
TI - Operational momentum in multiplication and division?
AB - Biases are commonly seen in numerical cognition. The operational momentum (OM)
effect shows that responses to addition and subtraction problems are biased in
the whole-number direction of the operation. It is not known if this bias exists
for other arithmetic operations. To determine whether OM exists in scalar
operations, we measured response bias in adults performing symbolic (Arabic
digits) and non-symbolic (dots) multiplication and division problems. After
seeing two operands, with either a multiplication (*) or division (/) sign,
participants chose among five response choices. Both non-random performance
profiles and the significant contribution of both operands in a multiple
regression analysis predicting the chosen values, suggest that adults were able
to use numerical information to approximate the outcomes in both notations,
though they were more accurate on symbolic problems. Performance on non-symbolic
problems was influenced by the size of the correct choice relative to
alternatives. Reminiscent of the bias in addition and subtraction, we found a
significant response bias for non-symbolic problems. Non-symbolic multiplication
problems were overestimated and division problems were underestimated. These
results indicate that operational momentum is present in non-symbolic
multiplication and division. Given the influence of the size of the correct
choice relative to alternatives, an interaction between heuristic bias and
approximate calculation is possible.
PMID- 25121953
TI - Overdiagnosis due to breast cancer screening: updated estimates of the Helsinki
service study in Finland.
AB - BACKGROUND: Overdiagnosis is the most important adverse event of breast cancer
screening with the estimates ranging from 0% to 40-50% depending on invitational
age and methods. We updated the estimates of overdiagnosis in Helsinki service
screening study in Finland by comparing the observed and expected cumulative
incidence of all breast carcinomas and invasive breast carcinomas. METHODS: Women
aged 50-59 years have been invited to Helsinki service screening since 1986. The
incidence of breast carcinoma in the first invited birth cohorts born in 1935
1939 was compared with older, non-invited cohorts. The minimum follow-up time of
the invitees after the last screening round was 14 years. Expected cumulative
incidence rates were estimated with two alternative approaches. RESULTS: For both
any breast carcinoma and invasive breast carcinoma, the estimates of
overdiagnosis varied from 5% (95% CI=-1, 11%) to 7% (95% CI=1, 13%) depending on
the approach. CONCLUSIONS: Our estimates of overdiagnosis are of the same
magnitude than other plausible estimates in Europe. Both alternative approaches
produced similar estimates for the expected cumulative incidence, which increased
the confidence in the estimates of overdiagnosis.
PMID- 25121954
TI - Comment on 'Pre-operative nomogram for the identification of lymph node
metastasis in early cervical cancer'.
PMID- 25121958
TI - Transition-state structure for the quintessential SN2 reaction of a carbohydrate:
reaction of alpha-glucopyranosyl fluoride with azide ion in water.
AB - We report that the SN2 reaction of alpha-d-glucopyranosyl fluoride with azide ion
proceeds through a loose (exploded) transition-state (TS) structure. We reached
this conclusion by modeling the TS using a suite of five experimental kinetic
isotope effects (KIEs) as constraints for the calculations. We also report that
the anomeric (13)C-KIE is not abnormally large (k12/k13 = 1.024 +/- 0.006), a
finding which is at variance with the previous literature value (Zhang et al. J.
Am. Chem. Soc. 1994, 116, 7557).
PMID- 25121956
TI - Serum protein profiling reveals baseline and pharmacodynamic biomarker signatures
associated with clinical outcome in mCRC patients treated with chemotherapy +/-
cediranib.
AB - BACKGROUND: This study evaluated soluble serum proteins as biomarkers to subset
patients with metastatic colorectal cancer (mCRC) treated with chemotherapy+/
cediranib, a vascular endothelial growth factor (VEGF) signalling inhibitor
(VEGFi). Exploring biomarkers at pre- and on-treatment may identify patient
subgroups showing clinical benefit on cediranib combination. METHODS: Two hundred
and seven serum proteins were analysed in 588 mCRC patients at pre- and on
treatment with chemotherapy (FOLFOX/CAPOX)+/-cediranib 20 mg. Patients were
enrolled in the phase III trial HORIZON II. We correlated baseline biomarker
signatures and pharmacodynamic (PD) biomarkers with PFS and OS. RESULTS: We
identified a baseline signature (BS) of 47 biomarkers that included VEGFA, VEGFD,
VEGFR2, VEGFR3 and TIE-2, which defined two distinct subgroups of patients.
Patients treated with chemotherapy plus cediranib who had 'high' BS had shorter
PFS (HR=1.82, P=0.003) than patients with 'low' BS. This BS did not correlate
with PFS of the patients treated with chemotherapy plus placebo. In addition, we
identified a profile of 16 PD proteins on treatment associated with PFS (HR=0.58,
P<0.001) and OS (HR=0.52, P<0.001) in patients treated with chemotherapy plus
cediranib. This PD profile did not correlate with PFS and OS in patients treated
with chemotherapy plus placebo. CONCLUSIONS: Serum proteins may represent
relevant biomarkers to predict the outcome of patients treated with VEGFi-based
therapies. We report a BS and PD biomarkers that may identify mCRC patients
showing increased benefit of combining cediranib with chemotherapy. These
exploratory findings need to be validated in future prospective studies.
PMID- 25121957
TI - Rapid detection of shrimp white spot syndrome virus by real time, isothermal
recombinase polymerase amplification assay.
AB - White spot syndrome virus (WSSV) causes large economic losses to the shrimp
aquaculture industry, and thus far there are no efficient therapeutic treatments
available against this lethal virus. In this study, we present the development of
a novel real time isothermal recombinase polymerase amplification (RPA) assay for
WSSV detection on a small ESEQuant Tube Scanner device. The RPA sensitivity,
specificity and rapidity were evaluated by using a plasmid standard as well as
viral and shrimp genomic DNAs. Compared with qPCR, the RPA assay revealed more
satisfactory performance. It reached a detection limit up to 10 molecules in 95%
of cases as determined by probit analysis of 8 independent experiments within
6.41 +/- 0.17 min at 39 degrees C. Consequently, this rapid RPA method has great
application potential for field use or point of care diagnostics.
PMID- 25121959
TI - Physical activity behavior and role overload in mothers.
AB - We examined physical activity stages of change, physical activity behavior, and
role overload in different stages of motherhood in a predominantly Australian
sample. Neither physical activity behavior, stages of physical activity change,
nor role overload significantly differed across motherhood groups. Role overload
was significantly higher for mothers in the contemplation, planning, and action
stages of physical activity than in the maintenance stage of change. Role
overload had a weak, although significant, negative correlation with leisure-time
physical activity. We conclude that strategies focused upon reducing role
overload or perceived role overload have only limited potential to meaningfully
increase leisure-time physical activity in mothers.
PMID- 25121955
TI - Flavonoid and lignan intake in relation to bladder cancer risk in the European
Prospective Investigation into Cancer and Nutrition (EPIC) study.
AB - BACKGROUND: There is growing evidence of the protective role of dietary intake of
flavonoids and lignans on cancer, but the association with bladder cancer has not
been thoroughly investigated in epidemiological studies. We evaluated the
association between dietary intakes of total and subclasses of flavonoids and
lignans and risk of bladder cancer and its main morphological type, urothelial
cell carcinoma (UCC), within the European Prospective Investigation into Cancer
and Nutrition (EPIC) study. METHODS: A cohort of 477 312 men and women mostly
aged 35-70 years, were recruited in 10 European countries. At baseline, dietary
flavonoid and lignan intakes were estimated using centre-specific validated
questionnaires and a food composition database based on the Phenol-Explorer, the
UK Food Standards Agency and the US Department of Agriculture databases. RESULTS:
During an average of 11 years of follow-up, 1575 new cases of primary bladder
cancer were identified, of which 1425 were UCC (classified into aggressive
(n=430) and non-aggressive (n=413) UCC). No association was found between total
flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant
inverse associations with bladder cancer risk were found for intakes of flavonol
(hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence
interval (CI): 0.61-0.91; P-trend=0.009) and lignans (HRQ5-Q1 0.78, 95% CI: 0.62
0.96; P-trend=0.046). Similar results were observed for overall UCC and
aggressive UCC, but not for non-aggressive UCC. CONCLUSIONS: Our study suggests
an inverse association between the dietary intakes of flavonols and lignans and
risk of bladder cancer, particularly aggressive UCC.
PMID- 25121960
TI - The population genetics of evolutionary rescue.
AB - Evolutionary rescue occurs when a population that is threatened with extinction
by an environmental change adapts to the change sufficiently rapidly to survive.
Here we extend the mathematical theory of evolutionary rescue. In particular, we
model evolutionary rescue to a sudden environmental change when adaptation
involves evolution at a single locus. We consider adaptation using either new
mutations or alleles from the standing genetic variation that begin rare. We
obtain several results: i) the total probability of evolutionary rescue from
either new mutation or standing variation; ii) the conditions under which rescue
is more likely to involve a new mutation versus an allele from the standing
genetic variation; iii) a mathematical description of the U-shaped curve of total
population size through time, conditional on rescue; and iv) the time until the
average population size begins to rebound as well as the minimal expected
population size experienced by a rescued population. Our analysis requires taking
into account a subtle population-genetic effect (familiar from the theory of
genetic hitchhiking) that involves "oversampling" of those lucky alleles that
ultimately sweep to high frequency. Our results are relevant to conservation
biology, experimental microbial evolution, and medicine (e.g., the dynamics of
antibiotic resistance).
PMID- 25121963
TI - Synthetic, structural, NMR and catalytic studies of phosphinic amide-phosphoryl
chalcogenides (chalcogen = O, S, Se) as mixed-donor bidentate ligands in zinc
chemistry.
AB - ortho Substituted (diphenylphosphoryl)-, (diphenylphosphorothioyl)- and
(diphenylphosphoroselenoyl)-phosphinic amides o-C6H4(P(X)Ph2)(P(O)N(i)Pr2) (X = O
(20a), S (20b), Se (20c)) were synthesized by ortho directed lithiation of N,N
diisopropyl-P,P-diphenylphosphinic amide (Ph2P(O)N(i)Pr2) followed by trapping
with Ph2PCl and subsequent oxidation of the o-(diphenylphosphine)phosphinic amide
(19) with H2O2, S8 and Se. The reaction of the new mixed-donor bidentate ligands
with zinc dichloride afforded the corresponding complexes [ZnCl2(P(X)Ph2)o
C6H4(P(O)N(i)Pr2)] (21a-c). The new compounds were structurally characterized in
solution by nuclear magnetic resonance spectroscopy and in the solid-state by X
ray diffraction analysis of the ligand (20b) and the three complexes (21a-c). The
X-ray crystal structure of 20b suggests the existence of a P[double bond, length
as m-dash]O->P(S)-C intramolecular nonbonded interaction. The natural bond
orbital (NBO) analysis using DFT methods showed that the stabilization effect
provided by a nO->sigma*P-C orbital interaction was negligible. The molecular
structure of the complexes consisted of seven-membered chelates formed by O,X
coordination of the ligands to the zinc cation. The metal is four-coordinated by
binding to the two chlorine atoms showing a distorted tetrahedral geometry.
Applications in catalysis revealed that hemilabile ligands 20a-c act as
significant promoters of the addition of diethylzinc to aldehydes, with 20a
showing the highest activity. Chelation of Et2Zn with 20a was evidenced by NMR
spectroscopy.
PMID- 25121961
TI - Awakening and withdrawal of life-sustaining treatment in cardiac arrest survivors
treated with therapeutic hypothermia*.
AB - OBJECTIVES: To characterize the prevalence of withdrawal of life-sustaining
treatment, as well as the time to awakening, short-term neurologic outcomes, and
cause of death in comatose survivors of out-of-hospital resuscitated
cardiopulmonary arrests treated with therapeutic hypothermia. DESIGN: Single
center, prospective observational cohort study of consecutive patients with out
of-hospital cardiopulmonary arrests. SETTING: Academic tertiary care hospital and
level one trauma center in Minneapolis, MN. PATIENTS: Adults with witnessed,
nontraumatic, out-of-hospital cardiopulmonary arrests regardless of initial
electrocardiographic rhythm with return of spontaneous circulation who were
admitted to an ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study
cohort included 154 comatose survivors of witnessed out-of-hospital
cardiopulmonary arrests who were admitted to an ICU during the 54-month study
period. One hundred eighteen patients (77%) were treated with therapeutic
hypothermia. The mean age was 59 years, 104 (68%) were men, and 83 (54%) had an
initial rhythm of ventricular tachycardia or fibrillation. Only eight of all 78
patients (10%) who died qualified as brain dead; and 81% of all patients (63 of
78) who died did so after withdrawal of life-sustaining treatment. Twenty of 56
comatose survivors (32%) treated with hypothermia who awoke (as defined by
Glasgow Motor Score of 6) and had good neurologic outcomes (defined as Cerebral
Performance Category 1-2) did so after 72 hours. CONCLUSIONS: Our study supports
delaying prognostication and withdrawal of life-sustaining treatment to beyond 72
hours in cases treated with therapeutic hypothermia. Larger multicenter
prospective studies are needed to better define the most appropriate time frame
for prognostication in comatose cardiac arrest survivors treated with therapeutic
hypothermia. These data are also consistent with the notion that a majority of
out-of-hospital cardiopulmonary arrest survivors die after a decision to
withdrawal of life-sustaining treatment and that very few of these survivors
progress to brain death.
PMID- 25121965
TI - Risk factors for cardiovascular disease in people with idiopathic pulmonary
fibrosis: a population-based study.
AB - OBJECTIVE: People with idiopathic pulmonary fibrosis (IPF) have been shown to be
at an increased risk for cardiovascular (CV) disease, but reasons for this are
unknown. The aim of this study was to compare the prevalence of common CV risk
factors in people with IPF and the general population and establish the incidence
of ischemic heart disease (IHD) and stroke after the diagnosis of IPF,
controlling for these risk factors. METHODS: We used data from a large, UK
primary care database to identify incident cases of IPF and matched general
population control subjects. We compared the prevalence of risk factors for CV
disease and prescription of CV medications in people with IPF (before diagnosis)
with control subjects from the general population and assessed the incidence of
IHD and stroke in people with IPF (after diagnosis) compared with control
subjects. RESULTS: We identified 3,211 cases of IPF and 12,307 control subjects.
Patients with IPF were more likely to have a record of hypertension (OR, 1.31;
95% CI, 1.19-1.44), and diabetes (OR, 1.20; 95% CI, 1.07-1.34) compared with
control subjects; they were also more likely to have been prescribed several CV
drugs. The rate of first-time IHD events was more than twice as high in patients
than control subjects (rate ratio, 2.32; 95% CI, 1.85-2.93; P < .001), but the
incidence of stroke was only marginally higher (P = .09). Rate ratios for IHD and
stroke were not altered substantially after adjusting for CV risk factors.
CONCLUSIONS: Several CV risk factors were more prevalent in people with IPF;
however, this did not account for the increased rate of IHD in this group of
patients.
PMID- 25121964
TI - 3-alkoxy-pyrrolo[1,2-b]pyrazolines as selective androgen receptor modulators with
ideal physicochemical properties for transdermal administration.
AB - We describe the synthesis and characterization of 3-alkoxy-pyrrolo[1,2
b]pyrazolines as novel selective androgen receptor (AR) modulators that possess
excellent physicochemical properties for transdermal administration. Compound 26
bound to human AR with an IC50 of 0.7 nM with great selectivity over other
nuclear hormone receptors and potently activated AR in a C2C12 muscle cell
reporter gene assay with an EC50 of 0.5 nM. It showed high aqueous solubility of
1.3 g/L at pH 7.4, and an in silico model as well as a customized parallel
artificial membrane permeability assay indicated good skin permeation. Indeed,
when measuring skin permeation through excised human skin, an excellent flux of 2
MUg/(cm(2).h) was determined without any permeation enhancers. In a 2 week
Hershberger model using castrated rats, the compound showed dose-dependent
effects fully restoring skeletal muscle weight at 0.3 mg/kg/day after
subcutaneous administration with high selectivity over prostate stimulation.
PMID- 25121962
TI - Strongyloidiasis--an insight into its global prevalence and management.
AB - BACKGROUND: Strongyloides stercoralis, an intestinal parasitic nematode, infects
more than 100 million people worldwide. Strongyloides are unique in their ability
to exist as a free-living and autoinfective cycle. Strongyloidiasis can occur
without any symptoms or as a potentially fatal hyperinfection or disseminated
infection. The most common risk factors for these complications are
immunosuppression caused by corticosteroids and infection with human T
lymphotropic virus or human immunodeficiency virus. Even though the diagnosis of
strongyloidiasis is improved by advanced instrumentation techniques in isolated
and complicated cases of hyperinfection or dissemination, efficient guidelines
for screening the population in epidemiological surveys are lacking. METHODOLOGY
AND RESULTS: In this review, we have discussed various conventional methods for
the diagnosis and management of this disease, with an emphasis on recently
developed molecular and serological methods that could be implemented to
establish guidelines for precise diagnosis of infection in patients and screening
in epidemiological surveys. A comprehensive analysis of various cases reported
worldwide from different endemic and nonendemic foci of the disease for the last
40 years was evaluated in an effort to delineate the global prevalence of this
disease. We also updated the current knowledge of the various clinical spectrum
of this parasitic disease, with an emphasis on newer molecular diagnostic
methods, treatment, and management of cases in immunosuppressed patients.
CONCLUSION: Strongyloidiasis is considered a neglected tropical disease and is
probably an underdiagnosed parasitic disease due to its low parasitic load and
uncertain clinical symptoms. Increased infectivity rates in many developed
countries and nonendemic regions nearing those in the most prevalent endemic
regions of this parasite and the increasing transmission potential to immigrants,
travelers, and immunosuppressed populations are indications for initiating an
integrated approach towards prompt diagnosis and control of this parasitic
disease.
PMID- 25121966
TI - Genome-wide association analysis of radiation resistance in Drosophila
melanogaster.
AB - BACKGROUND: Ionizing radiation is genotoxic to cells. Healthy tissue toxicity in
patients and radiation resistance in tumors present common clinical challenges in
delivering effective radiation therapies. Radiation response is a complex,
polygenic trait with unknown genetic determinants. The Drosophila Genetic
Reference Panel (DGRP) provides a model to investigate the genetics of natural
variation for sensitivity to radiation. METHODS AND FINDINGS: Radiation response
was quantified in 154 inbred DGRP lines, among which 92 radiosensitive lines and
62 radioresistant lines were classified as controls and cases, respectively. A
case-control genome-wide association screen for radioresistance was performed.
There are 32 single nucleotide polymorphisms (SNPs) associated with radio
resistance at a nominal p<10(-5); all had modest effect sizes and were common
variants with the minor allele frequency >5%. All the genes implicated by those
SNP hits were novel, many without a known role in radiation resistance and some
with unknown function. Variants in known DNA damage and repair genes associated
with radiation response were below the significance threshold of p<10(-5) and
were not present among the significant hits. No SNP met the genome-wide
significance threshold (p = 1.49 * 10(-7)), indicating a necessity for a larger
sample size. CONCLUSIONS: Several genes not previously associated with variation
in radiation resistance were identified. These genes, especially the ones with
human homologs, form the basis for exploring new pathways involved in radiation
resistance in novel functional studies. An improved DGRP model with a sample size
of at least 265 lines and ideally up to 793 lines is recommended for future
studies of complex traits.
PMID- 25121967
TI - Kinetic memory based on the enzyme-limited competition.
AB - Cellular memory, which allows cells to retain information from their environment,
is important for a variety of cellular functions, such as adaptation to external
stimuli, cell differentiation, and synaptic plasticity. Although
posttranslational modifications have received much attention as a source of
cellular memory, the mechanisms directing such alterations have not been fully
uncovered. It may be possible to embed memory in multiple stable states in
dynamical systems governing modifications. However, several experiments on
modifications of proteins suggest long-term relaxation depending on experienced
external conditions, without explicit switches over multi-stable states. As an
alternative to a multistability memory scheme, we propose "kinetic memory" for
epigenetic cellular memory, in which memory is stored as a slow-relaxation
process far from a stable fixed state. Information from previous environmental
exposure is retained as the long-term maintenance of a cellular state, rather
than switches over fixed states. To demonstrate this kinetic memory, we study
several models in which multimeric proteins undergo catalytic modifications
(e.g., phosphorylation and methylation), and find that a slow relaxation process
of the modification state, logarithmic in time, appears when the concentration of
a catalyst (enzyme) involved in the modification reactions is lower than that of
the substrates. Sharp transitions from a normal fast-relaxation phase into this
slow-relaxation phase are revealed, and explained by enzyme-limited competition
among modification reactions. The slow-relaxation process is confirmed by
simulations of several models of catalytic reactions of protein modifications,
and it enables the memorization of external stimuli, as its time course depends
crucially on the history of the stimuli. This kinetic memory provides novel
insight into a broad class of cellular memory and functions. In particular,
applications for long-term potentiation are discussed, including dynamic
modifications of calcium-calmodulin kinase II and cAMP-response element-binding
protein essential for synaptic plasticity.
PMID- 25121968
TI - WW domain folding complexity revealed by infrared spectroscopy.
AB - Although the intrinsic tryptophan fluorescence of proteins offers a convenient
probe of protein folding, interpretation of the fluorescence spectrum is often
difficult because it is sensitive to both global and local changes. Infrared (IR)
spectroscopy offers a complementary measure of structural changes involved in
protein folding, because it probes changes in the secondary structure of the
protein backbone. Here we demonstrate the advantages of using multiple probes,
infrared and fluorescence spectroscopy, to study the folding of the FBP28 WW
domain. Laser-induced temperature jumps coupled with fluorescence or infrared
spectroscopy have been used to probe changes in the peptide backbone on the
submillisecond time scale. The relaxation dynamics of the beta-sheets and beta
turn were measured independently by probing the corresponding IR bands assigned
in the amide I region. Using these wavelength-dependent measurements, we observe
three kinetics phases, with the fastest process corresponding to the relaxation
kinetics of the turns. In contrast, fluorescence measurements of the wild-type WW
domain and tryptophan mutants exhibit single-exponential kinetics with a lifetime
that corresponds to the slowest phase observed by infrared spectroscopy. Mutant
sequences provide evidence of an intermediate dry molten globule state. The
slowest step in the folding of this WW domain is the tight packing of the side
chains in the transition from the dry molten globule intermediate to the native
structure. This study demonstrates that using multiple complementary probes
enhances the interpretation of protein folding dynamics.
PMID- 25121969
TI - iNitro-Tyr: prediction of nitrotyrosine sites in proteins with general pseudo
amino acid composition.
AB - Nitrotyrosine is one of the post-translational modifications (PTMs) in proteins
that occurs when their tyrosine residue is nitrated. Compared with healthy
people, a remarkably increased level of nitrotyrosine is detected in those
suffering from rheumatoid arthritis, septic shock, and coeliac disease. Given an
uncharacterized protein sequence that contains many tyrosine residues, which one
of them can be nitrated and which one cannot? This is a challenging problem, not
only directly related to in-depth understanding the PTM's mechanism but also to
the nitrotyrosine-based drug development. Particularly, with the avalanche of
protein sequences generated in the postgenomic age, it is highly desired to
develop a high throughput tool in this regard. Here, a new predictor called
"iNitro-Tyr" was developed by incorporating the position-specific dipeptide
propensity into the general pseudo amino acid composition for discriminating the
nitrotyrosine sites from non-nitrotyrosine sites in proteins. It was demonstrated
via the rigorous jackknife tests that the new predictor not only can yield higher
success rate but also is much more stable and less noisy. A web-server for iNitro
Tyr is accessible to the public at http://app.aporc.org/iNitro-Tyr/. For the
convenience of most experimental scientists, we have further provided a protocol
of step-by-step guide, by which users can easily get their desired results
without the need to follow the complicated mathematics that were presented in
this paper just for the integrity of its development process. It has not escaped
our notice that the approach presented here can be also used to deal with the
other PTM sites in proteins.
PMID- 25121970
TI - Efficiency of dendritic cell vaccination against B16 melanoma depends on the
immunization route.
AB - Dendritic cells (DC) presenting tumor antigens are crucial to induce potent T
cell-mediated anti-tumor immune responses. Therefore DC-based cancer vaccines
have been established for therapy, however clinical outcomes are often poor and
need improvement. Using a mouse model of B16 melanoma, we found that the route of
preventive DC vaccination critically determined tumor control. While repeated DC
vaccination did not show an impact of the route of DC application on the
prevention of tumor growth, a single DC vaccination revealed that both the
imprinting of skin homing receptors and an enhanced proliferation state of
effector T cells was seen only upon intracutaneous but not intravenous or
intraperitoneal immunization. Tumor growth was prevented only by intracutaneous
DC vaccination. Our results indicate that under suboptimal conditions the route
of DC vaccination crucially determines the efficiency of tumor defense. DC-based
strategies for immunotherapy of cancer should take into account the immunization
route in order to optimize tissue targeting of tumor antigen specific T cells.
PMID- 25121972
TI - Making mock-FNA smears from fresh surgical pathology specimens to improve smear
preparation technique and to create cytohistological correlation series.
AB - BACKGROUND: Fine needle aspiration (FNA) cytology is a well-established
diagnostic method based on the microscopic interpretation of often scant
cytological material; therefore, experience, good technique and smear quality are
equally important in obtaining satisfactory results. AIMS OF STUDY: We studied
the use of fresh surgical pathology specimens for making so-called mock-FNA
smears with the potential of cytohistological correlation. Additionally, we
studied how this process aids the improvement of preparation technique and smear
quality. METHODS: Cytological aspirates from 32 fresh biopsy specimens from
various sites: lung (20), lymph nodes (6), and breast (6) were obtained, all with
a clinical diagnosis of tumor. Aspiration was performed from grossly palpable
tumors. 25 G needle and Cameco-type syringe holder was used with minimal or no
suction. RESULTS: Unfixed surgical specimens provided sufficient cytological
material that resulted in good quality smears. After standard processing of
specimens into microscopic sections from paraffin embedded tissues,
cytohistological case-series were created. No significant alteration was reported
in tissue architecture on hematoxylin-eosin stained sections after the aspiration
procedure. A gradual, but steady improvement was observed in smear quality just
after a few preparations. DISCUSSIONS AND CONCLUSIONS: Our study proved that
surgical specimens may be used as a source of cytological material to create
cytohistological correlation studies and also to improve FNA cytology skills. The
use of very fine gauge needle (25 G, 0,6 mm diameter) during the sampling process
does not alter tissue architecture therefore the final histopathological
diagnosis is not compromised. We conclude that by using fresh surgical specimens
useful cytohistological collections can be created both as a teaching resource
and as improving experience.
PMID- 25121973
TI - Pregnancy, maternal exposure to analgesic medicines, and leukemia in Brazilian
children below 2 years of age.
AB - Childhood leukemia etiology, and mainly the interactions of genetic and
environmental risk factors, remains largely unexplored. This national hospital
based case-control study was carried out in Brazil among children aged 0-23
months who were recruited at cancer and general hospitals in 13 states. Maternal
medicine intake during pregnancy, including analgesic intake, was assessed by
face-to-face interviews with the mothers of 231 leukemia patients and 411
controls. Unconditional logistic regression was used to ascertain crude and
adjusted odds ratios (ORs), and their 95% confidence intervals (CIs) for the
association between maternal analgesic use during pregnancy and early age
leukemia. Acetaminophen use during the first trimester of pregnancy showed an
OR=0.39 (95% CI 0.17-0.93) for acute lymphocytic leukemia and an OR=0.37 (95% CI
0.16-0.88) for use in the second trimester. For acute myeloid leukemia, an
OR=0.11 (95% CI 0.02-0.97) was found following acetaminophen use in the second
trimester. For acute lymphocytic leukemia, the exclusive use of dipyrone during
preconception showed an OR=1.63 (95% CI 1.06-2.53) and dipyrone intake during
lactation showed an OR=2.00 (95% CI 1.18-3.39). These results suggest that
acetaminophen use during pregnancy may protect against development of early age
leukemia in the offspring, whereas dipyrone use may act as a risk factor for such
an outcome.
PMID- 25121971
TI - Mechanical cell-matrix feedback explains pairwise and collective endothelial cell
behavior in vitro.
AB - In vitro cultures of endothelial cells are a widely used model system of the
collective behavior of endothelial cells during vasculogenesis and angiogenesis.
When seeded in an extracellular matrix, endothelial cells can form blood vessel
like structures, including vascular networks and sprouts. Endothelial
morphogenesis depends on a large number of chemical and mechanical factors,
including the compliancy of the extracellular matrix, the available growth
factors, the adhesion of cells to the extracellular matrix, cell-cell signaling,
etc. Although various computational models have been proposed to explain the role
of each of these biochemical and biomechanical effects, the understanding of the
mechanisms underlying in vitro angiogenesis is still incomplete. Most
explanations focus on predicting the whole vascular network or sprout from the
underlying cell behavior, and do not check if the same model also correctly
captures the intermediate scale: the pairwise cell-cell interactions or single
cell responses to ECM mechanics. Here we show, using a hybrid cellular Potts and
finite element computational model, that a single set of biologically plausible
rules describing (a) the contractile forces that endothelial cells exert on the
ECM, (b) the resulting strains in the extracellular matrix, and (c) the cellular
response to the strains, suffices for reproducing the behavior of individual
endothelial cells and the interactions of endothelial cell pairs in compliant
matrices. With the same set of rules, the model also reproduces network formation
from scattered cells, and sprouting from endothelial spheroids. Combining the
present mechanical model with aspects of previously proposed mechanical and
chemical models may lead to a more complete understanding of in vitro
angiogenesis.
PMID- 25121976
TI - Prevalence and incidence of diabetes in Stockholm County 1990-2010.
AB - BACKGROUND: Diabetes is on the rise in the western world, but data from
Scandinavia are inconsistent with indications of stable or even reverse trends.
To shed new light on this issue, we investigated diabetes trends in Stockholm
County 1990-2010, taking into account trends in risk factors and mortality.
METHODS: We used data from a large population-based quadrennial public health
survey conducted between 1990 and 2010 in Stockholm County (~ 2.1 million
inhabitants), supplemented with data from national registers. The age
standardized prevalence and incidence rates of diabetes and related risk factors
1990-2010 were estimated in adult inhabitants. We also modelled the influence of
potential risk factors on the diabetes trends and estimated the life time risk of
diabetes. RESULTS: The prevalence of diabetes was 4.6% (95% confidence interval
(CI); 4.5-4.8%) in 2010 compared to 2.8% (95% CI; 2.3-3.5%) in 1990. Between 1990
and 2002 the prevalence rose annually by 3.8% (95% CI; 2.1-5.5). Incidence rates
showed a similar pattern and rose by 3.0% (95% CI; 0.3-5.7%) annually 1990-2002.
The rising incidence was mainly attributable to increasing prevalence of
overweight/obesity, which rose by 46% during the observation period. In 2010, the
lifetime risk of adult onset diabetes was 28% (95% CI; 26-31%) in men and 19%
(95% CI; 17-21%) in women. CONCLUSIONS: Diabetes rates have been increasing in
Stockholm over the last decades, both in terms of incidence and prevalence, and
this development is most likely the result of increasing overweight and obesity
in the population.
PMID- 25121974
TI - Cardiovascular complications following chronic treatment with cocaine and
testosterone in adolescent rats.
AB - Concomitant use of anabolic androgenic steroids and cocaine has increased in the
last years. However, the effects of chronic exposure to these substances during
adolescence on cardiovascular function are unknown. Here, we investigated the
effects of treatment for 10 consecutive days with testosterone and cocaine alone
or in combination on basal cardiovascular parameters, baroreflex activity,
hemodynamic responses to vasoactive agents, and cardiac morphology in adolescent
rats. Administration of testosterone alone increased arterial pressure, reduced
heart rate (HR), and exacerbated the tachycardiac baroreflex response. Cocaine
treated animals showed resting bradycardia without changes in arterial pressure
and baroreflex activity. Combined treatment with testosterone and cocaine did not
affect baseline arterial pressure and HR, but reduced baroreflex-mediated
tachycardia. None of the treatments affected arterial pressure response to either
vasoconstrictor or vasodilator agents. Also, heart to body ratio and left and
right ventricular wall thickness were not modified by drug treatments. However,
histological analysis of left ventricular sections of animals subjected to
treatment with testosterone and cocaine alone and combined showed a greater
spacing between cardiac muscle fibers, dilated blood vessels, and fibrosis. These
data show important cardiovascular changes following treatment with testosterone
in adolescent rats. However, the results suggest that exposure to cocaine alone
or combined with testosterone during adolescence minimally affect cardiovascular
function.
PMID- 25121977
TI - Cost-utility analysis of a treatment advice to discontinue inappropriate long
term antidepressant use in primary care.
AB - BACKGROUND: Antidepressant prescriptions have increased exponentially, burdening
health care costs. OBJECTIVE: To evaluate the costs and effects of an
antidepressant cessation advice in case of inappropriate long-term use in primary
care, i.e. long-term usage without a (current) indication. METHODS: A economic
evaluation during 1-year follow-up was performed, from a societal perspective, as
part of a cluster-randomised controlled clinical trial (PANDA). Costs were
assessed using the Trimbos/iMTA questionnaire for costs associated with
psychiatric illness. Health-related quality of life was measured using the
EuroQol 5D. Outcome was costs per quality adjusted life year (QALY). Missing
values were estimated using multiple imputation, bootstrap simulations were
performed to address the uncertainty surrounding the incremental cost
effectiveness ratios (ICERs). RESULTS: There was no difference in average QALYs
between the intervention (0.70) and control group (0.72) [difference -0.02 (95%
CI -0.05 to 0.10)]. The intervention group, however, was less expensive than the
control group (total costs ?3636 versus ?5267, respectively). Most cost
effectiveness pairs were located in the south-west quadrant of the cost
effectiveness plane, implying the intervention was less effective but also less
costly. The ICER of the pooled data was ?70,180, meaning that for one QALY lost,
?70,180 is saved. CONCLUSIONS: This study shows that an antidepressant cessation
advice given to patients (and their FPs) with inappropriate long-term
antidepressant usage, albeit not effective, does seem to result in a reduction of
societal costs. This reduction in costs is mostly due to reduction of
productivity losses, possibly due to patient empowerment and loss of stigma.
PMID- 25121978
TI - Attitudes about providing HIV care: voices from publicly funded clinics in
California.
AB - BACKGROUND: As the enactment of health care reform becomes a reality in the USA,
it has been widely predicted that HIV+ patients will increasingly be cared for by
primary care physicians (PCPs), many of whom lack the experience to deliver full
spectrum HIV care. OBJECTIVE: To describe PCPs' preparedness for an influx of
HIV+ patients. METHODS: This qualitative study included interviews with 20 PCPs
from community health centres in California. We inquired about clinicians'
experiences with HIV, their strategies for dealing with unfamiliar aspects of
medicine and their management of complicated patients. We also identified the
clinicians' preferred types of information and consultation resources. RESULTS:
PCPs are not yet comfortable as providers of comprehensive HIV care; however,
they are dedicated to delivering excellent care to all of their patients,
regardless of disease process. Although they prefer to refer HIV+ patients to
centres of excellence, they are willing to adopt full responsibility when
necessary and believe they can deliver high-quality HIV care if provided with
adequate consultation and informational resources. CONCLUSIONS: The Affordable
Care Act will insure an estimated 20000 more HIV+ patients in California. With a
dwindling supply of HIV specialists, many of these patients will be principally
cared for by PCPs. PCPs will go to great lengths to ensure that HIV+ patients
receive superior care, but they need the support of HIV specialists to expand
their skills. Priority should be given to ensuring that expert consultation is
widely available to PCPs who find themselves caring for HIV+ patients.
PMID- 25121979
TI - Population-based Stroke Atlas for outcome prediction: method and preliminary
results for ischemic stroke from CT.
AB - BACKGROUND AND PURPOSE: Knowledge of outcome prediction is important in stroke
management. We propose a lesion size and location-driven method for stroke
outcome prediction using a Population-based Stroke Atlas (PSA) linking
neurological parameters with neuroimaging in population. The PSA aggregates data
from previously treated patients and applies them to currently treated patients.
The PSA parameter distribution in the infarct region of a treated patient enables
prediction. We introduce a method for PSA calculation, quantify its performance,
and use it to illustrate ischemic stroke outcome prediction of modified Rankin
Scale (mRS) and Barthel Index (BI). METHODS: The preliminary PSA was constructed
from 128 ischemic stroke cases calculated for 8 variants (various data
aggregation schemes) and 3 case selection variables (infarct volume, NIHSS at
admission, and NIHSS at day 7), each in 4 ranges. Outcome prediction for 9
parameters (mRS at 7th, and mRS and BI at 30th, 90th, 180th, 360th day) was
studied using a leave-one-out approach, requiring 589,824 PSA maps to be
analyzed. RESULTS: Outcomes predicted for different PSA variants are
statistically equivalent, so the simplest and most efficient variant aiming at
parameter averaging is employed. This variant allows the PSA to be pre-calculated
before prediction. The PSA constrained by infarct volume and NIHSS reduces the
average prediction error (absolute difference between the predicted and actual
values) by a fraction of 0.796; the use of 3 patient-specific variables further
lowers it by 0.538. The PSA-based prediction error for mild and severe outcomes
(mRS = [2]-[5]) is (0.5-0.7). Prediction takes about 8 seconds. CONCLUSIONS:
PSA-based prediction of individual and group mRS and BI scores over time is
feasible, fast and simple, but its clinical usefulness requires further studies.
The case selection operation improves PSA predictability. A multiplicity of PSAs
can be computed independently for different datasets at various centers and
easily merged, which enables building powerful PSAs over the community.
PMID- 25121980
TI - Emptying effect of massage on parotid gland radioiodine content.
AB - BACKGROUND: To prevent salivary dysfunction in thyroid cancer patients who have
undergone radioiodine ablation, massaging the parotid gland (PG) is presumed to
be helpful for the removal of radioiodine. The purpose of this study was to
evaluate the effect of PG massage in the removal of radioiodine from the PG.
METHODS: Forty-four patients (female, 38; 49.1 +/- 11.0 years) who underwent
total thyroidectomy followed by I-131 ablation were included in this prospective
study. Three serial salivary gland scans were performed 2 h after administration
of I-123 in thyroid hormone withdrawal status. The patients were divided into two
groups. There was a 1-min (or 2-min) interval between the first and second scans
for control, followed by the performance of PG massage for 1 min (or 2 min)
between the second and third scans. Changes in uptakes were calculated between
the first and second scans (control) and between the second and third scans
(massage). RESULTS: The mean change in uptake at the 1-min massage was 0.97 +/-
11.27%, whereas that at the 1-min control was 11.54 +/- 5.59% (P<0.001). The mean
change in uptake at the 2-min massage was also significantly lower than that at
the 2-min control (11.11 +/- 6.97 vs. -0.85 +/- 9.78%, P<0.001). However, no
statistical difference was observed between the mean changes in uptake after 1-
and 2-min massages (P=0.573). CONCLUSION: PG massage reduced the radioiodine
uptake in the PG, and the effect of PG massage for 1 min was comparable with that
of PG massage for 2 min. PG massage can be applied to thyroid cancer patients who
receive radioiodine therapy to reduce PG dysfunction.
PMID- 25121981
TI - Who Seeks Cita Con El Doctor? Twelve Years of Spanish-Language Radio Program
Targeting U.S. Latinos.
AB - PURPOSE: Spanish-dominant Latinos make up 13% of the U.S. population, and this
group is poorer and faces multiple threats to health compared with the general
population. Additionally, Spanish speakers face challenges accessing health
information that is often not available in Spanish. This study provides a
descriptive epidemiology of a unique, low-cost health information source: the
longest-running U.S.-based Spanish-language call-in radio health education
program. METHOD: From the universe of all calls 1999 to 2011, stratified random
sampling yielded 1,237 analyzed calls, which were manually coded for caller sex,
age, proxy status, and health concern. Descriptive statistics were used to
examine basic demographics of callers and call topics overall and by sex and
proxy caller status. RESULTS: Among all calls, the top three call-generating
health topics were specific symptoms/conditions, sexual/reproductive health, and
gastrointestinal concerns. The top nine topics were consistent among women, men,
and proxy callers; however, relative frequency of topics varied across groups.
Nearly one quarter of calls were initiated on behalf of someone, generally a
child, spouse or sibling, or parent. Sixty percent of callers were women; women
made 70% of proxy calls. CONCLUSION: Understanding the differences in information
seeking behaviors, information needs, and source preferences is important for
determining where and how to disseminate health information and may help explain
disparities in knowledge and health outcomes. The radio talk show format provides
a uniquely personal, culturally sensitive channel for meeting health information
needs of a vulnerable population while leveraging the cost-effectiveness and wide
reach of a mass medium.
PMID- 25121982
TI - Application of a socio-ecological model to mother-infant bed-sharing.
AB - Mother-infant bed-sharing has been associated with an increased risk of sleep
related infant deaths, and thus, health messaging has aimed to discourage this
behavior. Despite this messaging, bed-sharing remains a common practice in the
United States, especially among minority families. Moreover, rates of accidental
suffocation and strangulation in bed (often related to bed-sharing) are on the
rise, with Black infants at two to three times greater risk than Whites. Multiple
studies have identified risk factors for bed-sharing, but a gap remains between
findings and translation into interventions. The socio-ecological model (SEM) has
been suggested as a way to study and design interventions addressing complex
public health issues. This article reconceptualizes the literature on mother
infant bed-sharing using the SEM. PubMed, POPLINE, ERIC, and Psych Info were
searched for articles that (a) included bed-sharing as the outcome variable, (b)
were published between 2000 and 2013, (c) were conducted in the United States,
and (d) included quantitative comparison of more than one factor. The following
data were extracted: sample characteristics, bed-sharing definition, methods,
factors examined, key findings, and conclusions. Data were summarized into five
SEM levels--infant, maternal, family and household, and community and society,
nested within the historical context of race. Sixteen studies met inclusion
criteria. Significant factors associated with bed-sharing were present within
each SEM level of influence. Educational interventions may increase efficacy by
attending to multiple levels of the SEM, especially when implementing such
interventions within minority subpopulations. Using a harm reduction approach to
reducing the risk around bed-sharing may be one way to account for the multiple
influences on bed-sharing. The science and practice of minimizing mother-infant
bed-sharing may be advanced through use of the SEM.
PMID- 25121985
TI - Candida albicans pathogenicity and epithelial immunity.
PMID- 25121984
TI - Lipoprotein-apheresis reduces circulating microparticles in individuals with
familial hypercholesterolemia.
AB - Lipoprotein-apheresis (apheresis) removes LDL-cholesterol in patients with severe
dyslipidemia. However, reduction is transient, indicating that the long-term
cardiovascular benefits of apheresis may not solely be due to LDL removal.
Microparticles (MPs) are submicron vesicles released from the plasma membrane of
cells. MPs, particularly platelet-derived MPs, are increasingly being linked to
the pathogenesis of many diseases. We aimed to characterize the effect of
apheresis on MP size, concentration, cellular origin, and fatty acid
concentration in individuals with familial hypercholesterolemia (FH). Plasma and
MP samples were collected from 12 individuals with FH undergoing routine
apheresis. Tunable resistive pulse sensing (np200) and nanoparticle tracking
analysis measured a fall in MP concentration (33 and 15%, respectively; P < 0.05)
pre- to post-apheresis. Flow cytometry showed MPs were predominantly annexin V
positive and of platelet (CD41) origin both pre- (88.9%) and post-apheresis
(88.4%). Fatty acid composition of MPs differed from that of plasma, though
apheresis affected a similar profile of fatty acids in both compartments, as
measured by GC-flame ionization detection. MP concentration was also shown to
positively correlate with thrombin generation potential. In conclusion, we show
apheresis nonselectively removes annexin V-positive platelet-derived MPs in
individuals with FH. These MPs are potent inducers of coagulation and are
elevated in CVD; this reduction in pathological MPs could relate to the long-term
benefits of apheresis.
PMID- 25121986
TI - Efficacy of an internet-based problem-solving training for teachers: results of a
randomized controlled trial.
AB - OBJECTIVE: The primary purpose of this randomized controlled trial (RCT) was to
evaluate the efficacy of internet-based problem-solving training (iPST) for
employees in the educational sector (teachers) with depressive symptoms. The
results of training were compared to those of a waitlist control group (WLC).
METHODS: One-hundred and fifty teachers with elevated depressive symptoms (Center
for Epidemiologic Studies Depression Scale, CES-D >=16) were assigned to either
the iPST or WLC group. The iPST consisted of five lessons, including problem
solving and rumination techniques. Symptoms were assessed before the intervention
began and in follow-up assessments after seven weeks, three months, and six
months. The primary outcome was depressive symptom severity (CES-D). Secondary
outcomes included general and work-specific self-efficacy, perceived stress,
pathological worries, burnout symptoms, general physical and mental health, and
absenteeism. RESULTS: iPST participants displayed a significantly greater
reduction in depressive symptoms after the intervention (d=0.59, 95% CI 0.26
0.92), after three months (d=0.37, 95% CI 0.05-0.70) and after six months
(d=0.38, 95% CI 0.05-0.70) compared to the control group. The iPST participants
also displayed significantly higher improvements in secondary outcomes. However,
workplace absenteeism was not significantly affected. CONCLUSION: iPST is
effective in reducing symptoms of depression among teachers. Disseminated on a
large scale, iPST could contribute to reducing the burden of stress-related
mental health problems among teachers. Future studies should evaluate iPST
approaches for use in other working populations.
PMID- 25121983
TI - Epoxy alcohol synthase of the rice blast fungus represents a novel subfamily of
dioxygenase-cytochrome P450 fusion enzymes.
AB - The genome of the rice blast fungus Magnaporthe oryzae codes for two proteins
with N-terminal dioxygenase (DOX) and C-terminal cytochrome P450 (CYP) domains,
respectively. One of them, MGG_13239, was confirmed as 7,8-linoleate diol
synthase by prokaryotic expression. The other recombinant protein (MGG_10859)
possessed prominent 10R-DOX and epoxy alcohol synthase (EAS) activities. This
enzyme, 10R-DOX-EAS, transformed 18:2n-6 sequentially to 10(R)-hydroperoxy
8(E),12(Z)-octadecadienoic acid (10R-HPODE) and to 12S(13R)-epoxy-10(R)-hydroxy
8(E)-octadecenoic acid as the end product. Oxygenation at C-10 occurred by
retention of the pro-R hydrogen of C-8 of 18:2n-6, suggesting antarafacial
hydrogen abstraction and oxygenation. Experiments with (18)O2 and (16)O2 gas
confirmed that the epoxy alcohol was formed from 10R-HPODE, likely by heterolytic
cleavage of the dioxygen bond with formation of P450 compound I, and subsequent
intramolecular epoxidation of the 12(Z) double bond. Site-directed mutagenesis
demonstrated that the cysteinyl heme ligand of the P450 domain was required for
the EAS activity. Replacement of Asn(965) with Val in the conserved AsnGlnXaaGln
sequence revealed that Asn(965) supported formation of the epoxy alcohol. 10R-DOX
EAS is the first member of a novel subfamily of DOX-CYP fusion proteins of
devastating plant pathogens.
PMID- 25121988
TI - Personal Out-of-Pocket Health Expenses, United States, 1970.
AB - Money spent on medical and dental care is an important concern of many families.
To alleviate the burden, a large number of families carry health insurance to
cover much of this expense. However, there remain some direct out-of- pocket
health expenditures for many of us. During 1971 the Health Interview Survey
conducted a study to measure the out-of-pocket health expenses of the civilian
population not confined to institutions. A self-enumeration questionnaire was
mailed to some 11,970 households comprising a representative sample of the
Nation's households, the same sample as that used in the last quarter of 1970 for
the Health Interview Survey (see the "Source of Data" for details). Information
was requested on out-of-pocket expenditures in 1970 for hospital, doctor, dental,
or optical services, prescribed medicine, and other medical expenses for each
family member as well as the total amount of health insurance premiums (including
Medicare premiums) paid directly by the family during 1970. No attempt has been
made in the study to measure the total cost of medical and dental care, since it
is difficult, if not impossible, for family members to report the amounts paid
through insurance benefits, government programs such as Medicare and Medicaid,
welfare, philanthropy, and other third-party payers. The total amount of national
health expenditures, including out-of-pocket costs, is measured by the Social
Security Administration and reported in the Social Security Bulletin in several
annual series of reports. Another source of expenditure data is the Center for
Health Administration Studies of the University of Chicago.
PMID- 25121987
TI - Induced pluripotent stem cells without c-Myc ameliorate retinal oxidative damage
via paracrine effects and reduced oxidative stress in rats.
AB - PURPOSE: To investigate the efficacy and mechanisms of non-c-Myc induced
pluripotent stem cell (iPSC) transplantation in a rat model of retinal oxidative
damage. METHODS: Paraquat was intravitreously injected into Sprague-Dawley rats.
After non-c-Myc iPSC transplantation, retinal function was evaluated by
electroretinograms (ERGs). The generation of reactive oxygen species (ROS) was
determined by lucigenin- and luminol-enhanced chemiluminescence. The expression
of brain-derived neurotrophic factor, ciliary neurotrophic factor, basic
fibroblast growth factor (bFGF), stromal cell-derived factor (SDF)-1alpha, and
CXCR4 was measured by immunohistochemistry and ELISA. An in vitro study using SH
SY5Y cells was performed to verify the protective effects of SDF-1alpha. RESULTS:
Transplantation of non-c-Myc iPSCs effectively promoted the recovery of the b
wave ratio in ERGs and significantly ameliorated retinal damage. Non-c-Myc iPSC
transplantation decreased ROS production and increased the activities of
superoxide dismutase and catalase, thereby reducing retinal oxidative damage and
apoptotic cells. Moreover, non-c-Myc iPSC transplantation resulted in significant
upregulation of SDF-1alpha, followed by bFGF, accompanied by a significant
improvement in the ERG. In vitro studies confirmed that treatment with SDF-1alpha
significantly reduced apoptosis in a dose-dependent manner in SH-SY5Y cells. Most
transplanted cells remained in the subretinal space, with spare cells expressing
neurofilament M markers at day 28. Six months after transplantation, no tumor
formation was seen in animals with non-c-Myc iPSC grafts. CONCLUSIONS: We
demonstrated the potential benefits of non-c-Myc iPSC transplantation for
treating oxidative-damage-induced retinal diseases. SDF-1alpha and bFGF play
important roles in facilitating the amelioration of retinal oxidative damage
after non-c-Myc iPSC transplantation.
PMID- 25121990
TI - Antibiotic resistance: a primer and call to action.
AB - During the past century, discoveries of microorganisms as causes of infections
and antibiotics as effective therapeutic agents have contributed to significant
gains in public health in many parts of the world. Health agencies worldwide are
galvanizing attention toward antibiotic resistance, which is a major threat to
public health (Centers for Disease Control and Prevention, 2013; World Health
Organization, 2014). Some life scientists believe that we are approaching the
post-antibiotic age (Davies & Davies, 2010). The growing threat of antimicrobial
resistance is fueled by complex factors with biological, behavioral, and societal
aspects. This primer provides an overview of antibiotic resistance and its
growing burden on public health, the biological and behavioral mechanisms that
increase antibiotic resistance, and examples of where health communication
scholars can contribute to efforts to make our current antibiotic drugs last as
long as possible. In addition, we identify compelling challenges for current
communication theories and practices.
PMID- 25121989
TI - Mucin 5B promoter polymorphism is associated with susceptibility to interstitial
lung diseases in Chinese males.
AB - The variation of G>T in the MUC5B promoter (rs35705950) has been associated with
idiopathic pulmonary fibrosis (IPF) and familial interstitial pneumonia (FIP) in
Caucasians, but no information is available regarding this variant in the Chinese
population. We recruited 405 patients with interstitial lung diseases (ILD),
including 165 IPF patients and 2043 healthy controls, for genotyping the MUC5B
gene in the Chinese population. One hundred three patients with pneumonia and 360
patients with autoimmune diseases (ADs) were recruited as disease controls. Our
results indicated that the prevalence of the minor allele (T) of the polymorphism
rs35705950 in healthy Chinese subjects was approximately 0.66%, which was lower
than that described in the Caucasian population. The frequencies of the T allele
were 3.33% and 2.22% in IPF and ILD patients, respectively, and these values were
significantly higher than those of healthy controls (P = 0.001, OR = 4.332 for
IPF, and P = 0.002, OR = 2.855 for ILD). A stratified analysis showed that this
variant in MUC5B associated with the risk for ILD mainly in older male Chinese
subjects. No difference was observed between patients with pneumonia, AD
patients, and healthy controls.
PMID- 25121992
TI - Methylphenidate intoxication: somnolence as an uncommon clinical symptom and
proof of overdosing by increased serum levels of ritalinic acid.
AB - There is considerable evidence for an increase of methylphenidate (MPH) abuse;
thus, physicians might be confronted more frequently with MPH intoxications.
Possible symptoms of intoxications with MPH are orofacial, stereotypic movements
and tics as well as tachycardia, cardiac arrhythmias, arterial hypertension,
hyperthermia, hallucinations and epileptic seizures. Here we report a patient who
demonstrated somnolence as an uncommon clinical feature of MPH intoxication. The
patient exhibited subnormal MPH serum levels (3 MUg/l), however markedly
increased serum levels of ritalinic acid (821 MUg/l; inactive metabolite of MPH),
that finally confirmed the initially suspected MPH intoxication. Due to the short
half-life of orally administered MPH (t1/2~3 h) the sole measurement of MPH serum
levels might be misleading concerning the proof of MPH overdosing in some cases.
Parallel measurement of MPH and ritalinic acid is recommended in cases with
suspected MPH intoxication and insufficient anamnestic data.
PMID- 25121991
TI - Cost-effectiveness of collaborative care for depression in UK primary care:
economic evaluation of a randomised controlled trial (CADET).
AB - BACKGROUND: Collaborative care is an effective treatment for the management of
depression but evidence on its cost-effectiveness in the UK is lacking. AIMS: To
assess the cost-effectiveness of collaborative care in a UK primary care setting.
METHODS: An economic evaluation alongside a multi-centre cluster randomised
controlled trial comparing collaborative care with usual primary care for adults
with depression (n = 581). Costs, quality-adjusted life-years (QALYs), and
incremental cost-effectiveness ratios (ICER) were calculated over a 12-month
follow-up, from the perspective of the UK National Health Service and Personal
Social Services (i.e. Third Party Payer). Sensitivity analyses are reported, and
uncertainty is presented using the cost-effectiveness acceptability curve (CEAC)
and the cost-effectiveness plane. RESULTS: The collaborative care intervention
had a mean cost of L272.50 per participant. Health and social care service use,
excluding collaborative care, indicated a similar profile of resource use between
collaborative care and usual care participants. Collaborative care offered a mean
incremental gain of 0.02 (95% CI: -0.02, 0.06) quality-adjusted life-years over
12 months, at a mean incremental cost of L270.72 (95% CI: -202.98, 886.04), and
resulted in an estimated mean cost per QALY of L14,248. Where costs associated
with informal care are considered in sensitivity analyses collaborative care is
expected to be less costly and more effective, thereby dominating treatment as
usual. CONCLUSION: Collaborative care offers health gains at a relatively low
cost, and is cost-effective compared with usual care against a decision-maker
willingness to pay threshold of L20,000 per QALY gained. Results here support the
commissioning of collaborative care in a UK primary care setting.
PMID- 25121994
TI - Non-glutamatergic clozapine augmentation strategies: a review and meta-analysis.
AB - Persistent negative symptoms and cognitive impairment are major clinical problems
in the treatment of schizophrenia. There is no convincing evidence regarding the
efficacy of augmentation of clozapine with a second antipsychotic, ethyl
eicosapentaenoic acid (E-EPA), an antidepressant, a mood stabilizer or extract of
Ginkgo biloba in clozapine-resistant schizophrenia. We present an overview of
studies in which the potential clinical utility of the addition of non
glutamatergic agents to clozapine is assessed. We performed a meta-analysis on
the efficacy of both risperidone and aripiprazole compared to placebo. We
compared the effects of the addition of a second antipsychotic or an
antidepressant to clozapine on positive, negative, overall and affective symptoms
of schizophrenia in double-blind placebo-controlled trials.
PMID- 25121993
TI - Pegylated interferon pharmacokinetics and self-reported depressive symptoms
during antiviral treatment for chronic hepatitis C.
AB - BACKGROUND: Pegylated interferon-2a (PegIFN-2a)+ribavirin treatment for chronic
hepatitis C is often associated with depressive symptoms. Previous studies have
failed to explore whether PegIFN-2a pharmacokinetic variability plays an
etiologic role in PegIFN-2a-induced mood disorders. The objective of this
investigation was to evaluate the association between trough PegIFN-2a
concentration at treatment week 4 ("PegIFN-2a Cmin4") and an increase in
depressive symptoms. METHODS: Using data from Virahep-C, the association between
PegIFN-2a Cmin4 and the following depression outcomes were evaluated using the
Center for Epidemiological Studies-Depression scale (CES-D): (1) change in CES-D
score from baseline to week 12; (2) greatest difference in CES-D score between
baseline and weeks 4, 12, or 24; and (3) occurrence of severe depressive symptoms
(CES-D greater than 23) at weeks 4, 12, or 24. One post-hoc analysis examined
whether PegIFN-2a exposure during the first week of treatment was associated with
change in CES-D score from baseline to week 4. RESULTS: No significant
associations between PegIFN-2a Cmin4 and the depression outcomes were observed
(p>0.05). Exploratory analyses suggest a possible relationship between PegIFN-2a
exposure during the first week of therapy and CES-D score change from baseline to
week 4 (p=0.03). CONCLUSIONS: PegIFN-2a concentration levels from baseline to
week 4 do not predict the onset and severity of depressive symptoms during 24
weeks of antiviral therapy; however PegIFN-2a levels during the first week of
treatment may predict depressive symptoms in the first 4 weeks, earlier than
anticipated and warrants further exploration.
PMID- 25121997
TI - Palladium-catalyzed direct ortho-nitration of azoarenes using NO2 as nitro
source.
AB - A palladium-catalyzed direct ortho-nitration reaction of azoarenes was developed
in which NO2 was used as both nitro source and oxidant for the first time. The
nitration products were converted into o-aminoazoarenes or benzotriazole
derivatives by a simple reduction.
PMID- 25121998
TI - When meaning is useless.
AB - The aim of this study is to disentangle the relative contribution of semantic and
phonological representation in immediate serial recall. Indeed, short-term memory
(STM) performance could be enhanced by familiarity with the phonological form of
the word only or together with semantic information. Participants learned two
sets of words in an unknown language: for one set they acquired both phonology
and semantics, while for the other only phonology. After that, they performed two
immediate serial recall tasks involving either "phonology and semantics" or "only
phonology" words and one with untrained words. The analyses showed that the
trained lists did not differ from each other, while they did from the untrained
one. These data confirm that familiarity with the phonological form is sufficient
for immediate serial recall. Therefore, we argue that semantics is not required
for verbal STM, but knowledge of the phonological form is what matters.
PMID- 25121995
TI - The influence of body mass index, age and sex on inflammatory disease risk in
semi-captive Chimpanzees.
AB - Obesity and ageing are emerging issues in the management of captive primates,
including Chimpanzees, Pan troglodytes. Studies on humans show that obesity and
old age can independently increase the risk of inflammatory-associated diseases
indicated by elevated levels of pro-inflammatory cells and proteins in the blood
of older or obese compared to levels in younger or non-obese individuals. In
humans, sex can influence the outcomes of these risks. Health management of these
problems in chimpanzee populations requires an understanding of similarities and
differences of factors influencing inflammatory disease risks in humans and in
chimpanzees. We examined the relationship between age, sex and Body Mass Index
(BMI) with hematological biomarkers of inflammatory disease risk established for
humans which include the neutrophil to lymphocyte ratio (NLR), and neutrophil,
white blood cell (WBC), platelet microparticle and platelet counts. We found that
higher values of NLR, neutrophil count and platelet microparticle count were
associated with higher BMI values and older age indicating increased inflammation
risk in these groups; a similar pattern to humans. There was a strong sex by age
interaction on inflammation risk, with older males more at risk than older
females. In contrast to human studies, total WBC count was not influenced by BMI,
but like humans, WBC and platelet counts were lower in older individuals compared
to younger individuals. Our findings are similar to those of humans and suggest
that further insight on managing chimpanzees can be gained from extensive studies
of ageing and obesity in humans. We suggest that managing BMI should be an
integral part of health management in captive chimpanzee populations in order to
partially reduce the risk of diseases associated with inflammation. These results
also highlight parallels in inflammation risk between humans and chimpanzees and
have implications for understanding the evolution of inflammation related
diseases in apes.
PMID- 25121996
TI - Repair-related activation of hedgehog signaling in stromal cells promotes
intrahepatic hypothyroidism.
AB - Thyroid hormone (TH) is important for tissue repair because it regulates cellular
differentiation. Intrahepatic TH activity is controlled by both serum TH levels
and hepatic deiodinases. TH substrate (T4) is converted into active hormone (T3)
by deiodinase 1 (D1) but into inactive hormone (rT3) by deiodinase 3 (D3).
Although the relative expressions of D1 and D3 are known to change during liver
injury, the cell types and signaling mechanisms involved are unclear. We
evaluated the hypothesis that changes in hepatic deiodinases result from repair
related activation of the Hedgehog pathway in stromal cells. We localized
deiodinase expression, assessed changes during injury, and determined how
targeted manipulation of Hedgehog signaling in stromal cells impacted hepatic
deiodinase expression, TH content, and TH action in rodents. Humans with chronic
liver disease were also studied. In healthy liver, hepatocytes strongly expressed
D1 and stromal cells weakly expressed D3. During injury, hepatocyte expression of
D1 decreased, whereas stromal expression of D3 increased, particularly in
myofibroblasts. Conditionally disrupting Hedgehog signaling in myofibroblasts
normalized deiodinase expression. Repair-related changes in deiodinases were
accompanied by reduced hepatic TH content and TH-regulated gene expression. In
patients, this was reflected by increased serum rT3. Moreover, the decreases in
the free T3 to rT3 and free T4 to rT3 ratios distinguished advanced from mild
fibrosis, even in individuals with similar serum levels of TSH and free T4. In
conclusion, the Hedgehog-dependent changes in liver stromal cells drive repair
related changes in hepatic deiodinase expression that promote intrahepatic
hypothyroidism, thereby limiting exposure to T3, an important factor for cellular
differentiation.
PMID- 25121999
TI - 20 years of leptin: leptin at 20: an overview.
AB - Historically, adipose tissue was considered to be a passive storage vessel
discharging nutrients in times of famine and accumulating fat in times of
surfeit. This view changed with the identification of leptin as an adipocyte
hormone. Leptin functions as an afferent signal in a negative feedback loop that
regulates food intake and metabolism to maintain homeostatic control of adipose
tissue mass. Before this, the existence of a system maintaining homeostatic
control of energy balance was unclear. The identification of leptin has thus
uncovered a new endocrine system that also links changes in nutrition to adaptive
responses in most if not all other physiologic systems. Further studies have
revealed a set of clinical syndromes caused by leptin deficiency, including
lipodystrophy and hypothalamic amenorrhea. This work has led to new therapeutic
approaches for a number of human conditions and has also established a conceptual
framework for studying the pathogenesis of obesity.
PMID- 25122001
TI - The role of dipeptidyl peptidase 4 (DPP4) in the preservation of renal function:
DPP4 involvement in hemoglobin expression.
AB - In a previous study, we demonstrated that dipeptidyl peptidase 4 (DPP4)-deficient
rats were susceptible to reduced glomerular filtration rate as a result of
streptozotocin (STZ)-induced diabetes. Therefore, we proposed that DPP4 might be
responsible for the preservation of renal function. In this study, to verify the
role of DPP4 in the preservation of renal function, we performed a microarray
analysis of the kidneys of WT and DPP4-deficient rats after STZ treatment, and
gene expression analysis using rat kidneys, human embryonic kidney 293 (HEK293)
cells, and human renal cancer cells (CakI-1). The microarray analysis indicated
that the expression levels of the transporter activity, heme-binding, and
pheromone binding-related genes changed significantly. The results of gene
expression analysis indicated that there were no significant differences in the
expression levels of hemoglobin mRNA between the DPP4-deficient and WT rats;
however, the expression levels of hemoglobin mRNA in the kidneys of DPP4
deficient rats tended to decrease when compared with those of both the non-STZ
treated and STZ-treated WT rats. The expression levels of hemoglobin in HEK293
and Caki-1 cells were significantly decreased when DPP4 was knocked down by
siRNA, were significantly increased by the addition of soluble human DPP4, and
were also significantly increased by the addition of the DPP4 inhibitor,
sitagliptin. The expression level of DPP4 was also significantly increased by the
addition of sitagliptin in both cell types. Our findings indicate that DPP4
regulates the expression of the hemoglobin genes, and might play a role in the
preservation of renal function; however, the underlying mechanism of this
preservation remains to be elucidated.
PMID- 25122000
TI - Gastrin induces ductal cell dedifferentiation and beta-cell neogenesis after 90%
pancreatectomy.
AB - Induction of beta-cell mass regeneration is a potentially curative treatment for
diabetes. We have recently found that long-term gastrin treatment results in
improved metabolic control and beta-cell mass expansion in 95% pancreatectomised
(Px) rats. In this study, we investigated the underlying mechanisms of gastrin
induced beta-cell mass expansion after Px. After 90%-Px, rats were treated with
gastrin (Px+G) or vehicle (Px+V), pancreatic remnants were harvested on days 1,
3, 5, 7, and 14 and used for gene expression, protein immunolocalisation and
morphometric analyses. Gastrin- and vehicle-treated Px rats showed similar blood
glucose levels throughout the study. Initially, after Px, focal areas of
regeneration, showing mesenchymal cells surrounding ductal structures that
expressed the cholecystokinin B receptor, were identified. These focal areas of
regeneration were similar in size and cell composition in the Px+G and Px+V
groups. However, in the Px+G group, the ductal structures showed lower levels of
keratin 20 and beta-catenin (indicative of duct dedifferentiation) and higher
levels of expression of neurogenin 3 and NKX6-1 (indicative of endocrine
progenitor phenotype), as compared with Px+V rats. In Px+G rats, beta-cell mass
and the number of scattered beta-cells were significantly increased compared with
Px+V rats, whereas beta-cell replication and apoptosis were similar in the two
groups. These results indicate that gastrin treatment-enhanced dedifferentiation
and reprogramming of regenerative ductal cells in Px rats, increased beta-cell
neogenesis and fostered beta-cell mass expansion.
PMID- 25122002
TI - UCP1 is present in porcine adipose tissue and is responsive to postnatal leptin.
AB - Intrauterine growth restriction (IUGR) may be accompanied by inadequate
thermoregulation, especially in piglets that are not considered to possess any
brown adipose tissue (BAT) and are thus entirely dependent on shivering
thermogenesis in order to maintain body temperature after birth. Leptin can
stimulate heat production by promoting non-shivering thermogenesis in BAT, but
whether this response occurs in piglets is unknown. Newborn female piglets that
were characterised as showing IUGR (mean birth weight of approximately 0.98 kg)
were therefore administered injections of either saline or leptin once a day for
the first 5 days of neonatal life. The dose of leptin was 0.5 mg/kg, which is
sufficient to increase plasma leptin by approximately tenfold and on the day of
birth induced a rapid increase in body temperature to values similar to those of
normal-sized 'control' piglets (mean birth weight of ~1.47 kg). Perirenal adipose
tissue was then sampled from all offspring at 21 days of age and the presence of
the BAT-specific uncoupling protein 1 (UCP1) was determined by
immunohistochemistry and immunoblotting. UCP1 was clearly detectable in all
samples analysed and its abundance was significantly reduced in the IUGR piglets
that had received saline compared with controls, but was raised to the same
amount as in controls in those IUGR females given leptin. There were no
differences in gene expression between primary markers of brown and white adipose
tissues between groups. In conclusion, piglets possess BAT that when stimulated
exogenously by leptin can promote increased body temperature.
PMID- 25122003
TI - Urocortin 3 activates AMPK and AKT pathways and enhances glucose disposal in rat
skeletal muscle.
AB - Insulin resistance (IR) in skeletal muscle is an important component of both type
2 diabetes and the syndrome of sarcopaenic obesity, for which there are no
effective therapies. Urocortins (UCNs) are not only well established as
neuropeptides but also have their roles in metabolism in peripheral tissues. We
have shown recently that global overexpression of UCN3 resulted in muscular
hypertrophy and resistance to the adverse metabolic effects of a high-fat diet.
Herein, we aimed to establish whether short-term local UCN3 expression could
enhance glucose disposal and insulin signalling in skeletal muscle. UCN3 was
found to be expressed in right tibialis cranialis and extensor digitorum longus
muscles of rats by in vivo electrotransfer and the effects studied vs the
contralateral muscles after 1 week. No increase in muscle mass was detected, but
test muscles showed 19% larger muscle fibre diameter (P=0.030), associated with
increased IGF1 and IGF1 receptor mRNA and increased SER256 phosphorylation of
forkhead transcription factor. Glucose clearance into the test muscles after an
intraperitoneal glucose load was increased by 23% (P=0.018) per unit mass,
associated with increased GLUT1 (34% increase; P=0.026) and GLUT4 (48% increase;
P=0.0009) proteins, and significantly increased phosphorylation of insulin
receptor substrate-1, AKT, AKT substrate of 160 kDa, glycogen synthase kinase
3beta, AMP-activated protein kinase and its substrate acetyl coA carboxylase.
Thus, UCN3 expression enhances glucose disposal and signalling in muscle by an
autocrine/paracrine mechanism that is separate from its pro-hypertrophic effects,
implying that such a manipulation may have promised for the treatment of IR
syndromes including sarcopaenic obesity.
PMID- 25122004
TI - Hepatitis B virus subgenotype A1: evolutionary relationships between Brazilian,
African and Asian isolates.
AB - Brazil is a country of low hepatitis B virus (HBV) endemicity in which the
genotype A of HBV (HBV/A) is the most prevalent. The complete nucleotide
sequences of 26 HBV/A isolates, originating from eight Brazilian states, were
determined. All were adw2. Twenty-three belonged to subgenotype A1 and three to
A2. By phylogenetic analysis, it was shown that all the 23 HBV/A1 isolates
clustered together with isolates from Bangladesh, India, Japan, Nepal, the
Philippines and United Arab Emirates, but not with those of Congo, Kenya, Malawi,
Rwanda, South Africa, Tanzania, Uganda and Zimbabwe. Four amino acid residues in
the polymerase (His138 in the terminal protein domain, Pro18 and His90 in the
spacer, and Ser109 in the reverse transcriptase), and one (Phe17) in the precore
region, predominated in Latin American and Asian HBV/A1 isolates, but were rarely
encountered in African isolates, with the exception of those from Somalia.
Specific variations of two adjacent amino acids in the C-terminal domain of the
HBx protein, namely Ala146 and Pro147, were found in all the Brazilian, but
rarely in the other HBV/A1 isolates. By Bayesian analysis, the existence of an
'Asian-American' clade within subgenotype A1 was supported by a posterior
probability value of 0.996. The close relatedness of the Brazilian, Asian and
Somalian isolates suggests that the HBV/A1 strains predominant in Brazil did not
originate from the five million slaves who were imported from Central and Western
Africa from 1551 to 1840, but rather from the 300-400,000 captives forcibly
removed from southeast Africa at the middle of the 19th century.
PMID- 25122006
TI - The meaningful use of electronic health records and health care quality.
AB - The federal government is investing approximately $30 billion in incentives for
adoption and meaningful use (MU) of electronic health records (EHRs). Whether
achieving MU improves quality of care is unclear. The researchers conducted a
longitudinal study of 514 primary care physicians in New York State from 2010 to
2011. Quality of care provided by those who achieved stage 1 MU was compared with
the quality provided by those who used EHRs but did not achieve stage 1 MU.
Generalized estimating equations were used to determine whether receipt of MU
incentives was independently associated with performance on 9 MU quality
measures. In 2011, 44% of physicians achieved MU and 56% did not. No difference
in quality was found between those who achieved stage 1 MU and those who were
using EHRs but had not achieved MU. Longer follow-up is needed to observe the
full effects of this multistage national policy.
PMID- 25122005
TI - Role of vascular smooth muscle PPARgamma in regulating AT1 receptor signaling and
angiotensin II-dependent hypertension.
AB - Peroxisome proliferator activated receptor gamma (PPARgamma) has been reported to
play a protective role in the vasculature; however, the underlying mechanisms
involved are not entirely known. We previously showed that vascular smooth muscle
specific overexpression of a dominant negative human PPARgamma mutation in mice
(S-P467L) leads to enhanced myogenic tone and increased angiotensin-II-dependent
vasoconstriction. S-P467L mice also exhibit increased arterial blood pressure.
Here we tested the hypotheses that a) mesenteric smooth muscle cells isolated
from S-P467L mice exhibit enhanced angiotensin-II AT1 receptor signaling, and b)
the increased arterial pressure of S-P467L mice is angiotensin-II AT1 receptor
dependent. Phosphorylation of mitogen-activated protein/extracellular signal
regulated kinase (ERK1/2) was robustly increased in mesenteric artery smooth
muscle cell cultures from S-P467L in response to angiotensin-II. The increase in
ERK1/2 activation by angiotensin-II was blocked by losartan, a blocker of AT1
receptors. Angiotensin-II-induced ERK1/2 activation was also blocked by Tempol, a
scavenger of reactive oxygen species, and correlated with increased Nox4 protein
expression. To investigate whether endogenous renin-angiotensin system activity
contributes to the elevated arterial pressure in S-P467L, non-transgenic and S
P467L mice were treated with the AT1 receptor blocker, losartan (30 mg/kg per
day), for 14-days and arterial pressure was assessed by radiotelemetry. At
baseline S-P467L mice showed a significant increase of systolic arterial pressure
(142.0 +/- 10.2 vs 129.1 +/- 3.0 mmHg, p<0.05). Treatment with losartan lowered
systolic arterial pressure in S-P467L (132.2 +/- 6.9 mmHg) to a level similar to
untreated non-transgenic mice. Losartan also lowered arterial pressure in non
transgenic (113.0 +/- 3.9 mmHg) mice, such that there was no difference in the
losartan-induced depressor response between groups (-13.53 +/- 1.39 in S-P467L vs
-16.16 +/- 3.14 mmHg in non-transgenic). Our results suggest that interference
with PPARgamma in smooth muscle: a) causes enhanced angiotensin-II AT1 receptor
mediated ERK1/2 activation in resistance vessels, b) and may elevate arterial
pressure through both angiotensin-II AT1 receptor-dependent and -independent
mechanisms.
PMID- 25122008
TI - A supersandwich electrochemiluminescence immunosensor based on mimic
intramolecular interaction for sensitive detection of proteins.
AB - An electrochemiluminescence (ECL) immunoassay protocol was developed based on
mimic-intramolecular interaction for sensitive detection of prostate specific
antigen (PSA). It was constructed by integrating the ECL luminophore (tris(4,4'
dicarboxylicacid-2,2'-bipyridyl)-ruthenium(ii)dichloride (Ru(dcbpy)3(2+))) and
coreactant (histidine) into the supersandwich DNA structure. This strategy was
more effective in amplifying the ECL signal by shortening the electronic
transmission distance, improving the ECL luminous stability and enhancing the ECL
luminous efficiency. The ECL matrices denoted as MWCNTs@PDA-AuNPs were fabricated
through spontaneous oxidative polymerization of dopamine (DA) on multiwalled
carbon nanotubes (MWCNTs) and reducing HAuCl4 to produce gold nanoparticles
(AuNPs) by DA simultaneously. Then, the prepared matrices were applied to bind
capture antibodies. Moreover, supersandwich Ab2 bioconjugate was designed using a
PAMAM dendrimer to immobilize the detection antibody and supersandwich DNA
structure. The PAMAM dendrimer, with a plurality of secondary and tertiary amine
groups, not only facilitated high-density immobilization of the detection
antibody and supersandwich DNA structure, but also greatly amplified the ECL
signal of Ru(dcbpy)3(2+). The supersandwich DNA structure contained multiple
Ru(dcbpy)3(2+) and histidine, further amplifying the ECL signal. The proposed
supersandwich immunosensor showed high sensitivity with a detection limit of 4.2
fg mL(-1) and a wide linear range of 0.01 pg mL(-1)-40.00 ng mL(-1). With the
excellent stability, satisfying precision and reproducibility, the proposed
immunosensor indicates promising practicability for clinical diagnosis.
PMID- 25122009
TI - Workers: the climate canaries.
PMID- 25122007
TI - Lymphocyte Activation Gene-3 (LAG-3) negatively regulates environmentally-induced
autoimmunity.
AB - Environmental factors including drugs, mineral oils and heavy metals such as
lead, gold and mercury are triggers of autoimmune diseases in animal models or
even in occupationally exposed humans. After exposure to subtoxic levels of
mercury (Hg), genetically susceptible strains of mice develop an autoimmune
disease characterized by the production of highly specific anti-nucleolar
autoantibodies, hyperglobulinemia and nephritis. However, mice can be tolerized
to the disease by a single low dose administration of Hg. Lymphocyte Activation
Gene-3 (LAG-3) is a CD4-related, MHC-class II binding molecule expressed on
activated T cells and NK cells which maintains lymphocyte homeostatic balance via
various inhibitory mechanisms. In our model, administration of anti-LAG-3
monoclonal antibody broke tolerance to Hg resulting in autoantibody production
and an increase in serum IgE level. In addition, LAG-3-deficient B6.SJL mice not
only had increased susceptibility to Hg-induced autoimmunity but were also
unresponsive to tolerance induction. Conversely, adoptive transfer of wild-type
CD4(+) T cells was able to partially rescue LAG-3-deficient mice from the
autoimmune disease. Further, in LAG-3-deficient mice, mercury elicited higher
amounts of IL-6, IL-4 and IFN-gamma, cytokines known to play a critical role in
mercury-induced autoimmunity. Therefore, we conclude that LAG-3 exerts an
important regulatory effect on autoimmunity elicited by a common environmental
pollutant.
PMID- 25122010
TI - Epigenome: biosensor of cumulative exposure to chemical and nonchemical stressors
related to environmental justice.
AB - Understanding differential disease susceptibility requires new tools to quantify
the cumulative effects of environmental stress. Evidence suggests that social,
physical, and chemical stressors can influence disease through the accumulation
of epigenetic modifications. Geographically stable epigenetic alterations could
identify plausible mechanisms for health disparities among the disadvantaged and
poor. Relations between neighborhood-specific epigenetic markers and disease
would identify the most appropriate targets for medical and environmental
intervention. Complex interactions among genes, the environment, and disease
require the examination of how epigenetic changes regulate susceptibility to
environmental stressors. Progress in understanding disparities in disease
susceptibility may depend on assessing the cumulative effect of environmental
stressors on genetic substrates. We highlight key concepts regarding the
interface between environmental stress, epigenetics, and chronic disease.
PMID- 25122011
TI - Why is life expectancy declining among low-educated women in the United States?
PMID- 25122012
TI - Is science public health's BFF?
PMID- 25122013
TI - Dentist supply and children's oral health in the United States.
AB - OBJECTIVES: We evaluated the relationship between dentist supply and children's
oral health and explored heterogeneity by children's age and urbanicity. METHODS:
We obtained data from the 2007 National Survey of Children's Health (>27,000
children aged 1-10 years; >23,000 children aged 11-17 years). We estimated the
association between state-level dentist supply and multiple measures of
children's oral health using regression analysis adjusting for several child,
family, and population-level characteristics. RESULTS: Dentist supply was
significantly related to better oral health outcomes among children aged 1 to 10
years. The odds of decay and bleeding gums were lower by more than 50% (odds
ratio [OR]=0.46; 95% CI=0.23, 0.95) and 80% (OR=0.18; 95% CI=0.05, 0.76),
respectively, with an additional dentist per 1000 population. The odds of a worse
maternal rating of child's dental health on a 5-category scale from poor to
excellent were lower by about 50% in this age group with an additional dentist
per 1000 population (OR=0.51; 95% CI=0.29, 0.91). We observed associations only
for children in urban settings. CONCLUSIONS: Dentist supply is associated with
improved oral health for younger children in urban settings.
PMID- 25122014
TI - Insidious trends and social/environmental justice: public health's challenge for
responding to hazard events.
PMID- 25122016
TI - Fleming et al. respond.
PMID- 25122015
TI - Use of research evidence in state policymaking for childhood obesity prevention
in Minnesota.
AB - OBJECTIVES: We describe how scientific evidence about obesity has been used in
Minnesota legislative materials to understand how research evidence might more
effectively be translated into policymaking. METHODS: We selected 13 obesity
related bills introduced from 2007 to 2011 in Minnesota. Using state archives, we
collected all legislative committee meeting materials and floor testimony related
to each bill. We used a coding instrument to systematically analyze the content
of a sample of 109 materials for their use of research evidence and non-research
based information. RESULTS: Research evidence was mentioned in 41% of all
legislative materials. Evidence was often used to describe the prevalence or
consequences of obesity or policy impacts but not to describe health disparities.
In 45% of materials that cited evidence, no source of evidence was indicated. By
contrast, 92% of materials presented non-research-based information, such as
expert beliefs, constituent opinion, political principles, and anecdotes.
CONCLUSIONS: Despite an abundance of available research evidence on obesity, less
than half of legislative materials cited any such evidence in discussions around
obesity-related bills under consideration in Minnesota.
PMID- 25122017
TI - The alcohol policy environment and policy subgroups as predictors of binge
drinking measures among US adults.
AB - OBJECTIVES: We examined the relationships of the state-level alcohol policy
environment and policy subgroups with individual-level binge drinking measures.
METHODS: We used generalized estimating equations regression models to relate the
alcohol policy environment based on data from 29 policies in US states from 2004
to 2009 to 3 binge drinking measures in adults from the 2005 to 2010 Behavioral
Risk Factor Surveillance System surveys. RESULTS: A 10 percentage point higher
alcohol policy environment score, which reflected increased policy effectiveness
and implementation, was associated with an 8% lower adjusted odds of binge
drinking and binge drinking 5 or more times, and a 10% lower adjusted odds of
consuming 10 or more drinks. Policies that targeted the general population rather
than the underage population, alcohol consumption rather than impaired driving,
and raising the price or reducing the availability of alcohol had the strongest
independent associations with reduced binge drinking. Alcohol taxes and outlet
density accounted for approximately half of the effect magnitude observed for all
policies. CONCLUSIONS: A small number of policies that raised alcohol prices and
reduced its availability appeared to affect binge drinking.
PMID- 25122018
TI - The tobacco industry, researchers, and ethical access to UK Biobank: using the
public interest and public good.
AB - We have asked whether the strategic purpose of the tobacco industry is something
that a public resource, such as UK Biobank, should support. Tobacco industry
health research has been known to work irreconcilably with the purposes of such
institutions, which can be surmised as for the public good and defined to improve
the provision, diagnosis, and treatment of illness and the promotion of health
throughout society. We have isolated possible conflicts of interest that underlie
vested research agendas of the tobacco industry and that may extend to tobacco
industry-funded researchers. With respect to research, we find that the tobacco
industry is entirely at odds with the purposes of public biobanking.
PMID- 25122020
TI - Moving upstream: why rehabilitative justice in military discharge proceedings
serves a public health interest.
AB - The cultural divide between US military and civilian institutions amplifies the
consequences of military discharge status on public health and criminal justice
systems in a manner that is invisible to a larger society. Prompt removal of
problematic wounded warriors through retributive justice is more expedient than
lengthy mental health treatment. Administrative and punitive discharges usually
preclude Department of Veterans Affairs eligibility, posing a heavy public health
burden. Moving upstream--through military rehabilitative justice addressing
military offenders' mental health needs before discharge--will reduce the
downstream consequences of civilian maladjustment and intergenerational
transmission of mental illness. The public health community can play an
illuminating role by gathering data about community effect and by advocating for
policy change at Department of Veterans Affairs and community levels.
PMID- 25122019
TI - Systematic review of the effect of pictorial warnings on cigarette packages in
smoking behavior.
AB - We used a structured approach to assess whether active smokers presented with
pictorial warnings on cigarette packages (PWCP) had a higher probability of
quitting, reducing, and attempting to quit smoking than did unexposed smokers. We
identified 21 articles from among nearly 2500 published between 1993 and 2013,
prioritizing coverage over relevance or quality because we expected to find only
a few studies with behavioral outcomes. We found very large heterogeneity across
studies, poor or very poor methodological quality, and generally null or
conflicting findings for any explored outcome. The evidence for or against the
use of PWCP is insufficient, suggesting that any effect of PWCP on behavior would
be modest. Determining the single impact of PWCP on behavior requires studies
with strong methodological designs and longer follow-up periods.
PMID- 25122021
TI - Patterns of visit attendance in the nurse-family partnership program.
AB - OBJECTIVES: We examined visit attendance patterns in the Memphis trial of the
Nurse-Family Partnership and associations between these patterns and family
characteristics, outcomes, and treatment-control differences in outcomes.
METHODS: We employed repeated measures latent class analysis to identify
attendance patterns among the 228 mothers assigned to receive home nurse visits
during pregnancy and until the child was aged 2 years, associated background
characteristics, outcomes, and treatment-control differences by visit class. Home
visits were conducted from June 1990 to March 1994. We collected outcome data
from May 1992 to April 1994 and July 2003 to December 2006. RESULTS: We
identified 3 visit attendance patterns. High attenders (48%) had the most visits
and good outcomes. Low attenders (33%) had the most education and the best
outcomes. Increasing attenders (18%) had the fewest completed visits during
pregnancy, the poorest intake characteristics, and the poorest outcomes.
Treatment-control group differences varied by class, with high and low attenders
having better outcomes on some measures than did their control group
counterparts. CONCLUSIONS: Three patterns were associated with distinct groups of
mothers with different long-term outcomes. Further examination and use of
patterns to classify mothers and prioritize resources may improve efficiency in
the Nurse-Family Partnership.
PMID- 25122022
TI - Integrating health into disaster risk reduction strategies: key considerations
for success.
AB - The human and financial costs of disasters are vast. In 2011, disasters were
estimated to have cost $378 billion worldwide; disasters have affected 64% of the
world's population since 1992. Consequently, disaster risk reduction strategies
have become increasingly prominent on national and international policy agendas.
However, the function of health in disaster risk reduction strategies often has
been restricted to emergency response. To mitigate the effect of disasters on
social and health development goals (such as risk reduction Millennium
Development Goals) and increase resilience among at-risk populations, disaster
strategies should assign the health sector a more all-encompassing, proactive
role. We discuss proposed methods and concepts for mainstreaming health in
disaster risk reduction and consider barriers faced by the health sector in this
field.
PMID- 25122023
TI - On the value of the "Man Up Monday" campaign.
PMID- 25122025
TI - Reproductive rights denied: the Hyde Amendment and access to abortion for Native
American women using Indian health service facilities.
AB - Restrictions on the use of federal funds to provide abortions have limited the
access to abortion services for Native American women receiving care at Indian
Health Service facilities. Current data suggest that the vast majority of Indian
Health Service facilities are unequipped to provide abortions under any
circumstances. Native American women experience disproportionately high rates of
sexual assault and unintended pregnancy. Hyde Amendment restrictions
systematically infringe on the reproductive rights of Native American women and
present a pressing public health policy concern.
PMID- 25122024
TI - Implementation of tobacco cessation quitline practices in the United States and
Canada.
AB - OBJECTIVES: We examined relationships between implementation of tobacco quitline
practices, levels of evidence of practices, and quitline reach and spending.
METHODS: In June and July 2009, a total of 176 quitline funders and providers in
the United States and Canada completed a survey on quitline practices, in
particular quitline-level implementation for the reported practices. From these
data, we selected and categorized evidence-based and emerging quitline practices
by the strength of the evidence for each practice to increase quitline efficacy
and reach. RESULTS: The proportion of quitlines implementing each practice ranged
from 3% (text messaging) to 92% (providing a multiple-call protocol).
Implementation of practices showing higher levels of evidence for increasing
either reach or efficacy showed moderate but significant positive correlations
with both reach outcomes and spending levels. The strongest correlation was
between reach outcomes and spending levels (r=0.80; P<.01). CONCLUSIONS: The
strong relationship between quitline spending and reach reinforces the need to
increase quitline funding to levels commensurate with national cessation goals.
PMID- 25122026
TI - Evaluating the implementation process of a citywide smoke-free multiunit housing
ordinance: insights from community stakeholders.
AB - We evaluated the implementation process of Richmond, California's citywide smoke
free multiunit housing ordinance. We conducted semistructured focus groups with
multiunit housing tenants, owners, and managers. Residents understood the harms
of secondhand smoke but lacked accurate information about the ordinance and
questioned its enforceability. They shared concerns that the city lacked
cessation resources for smokers wishing to quit because of the ordinance. To
increase compliance with the ordinance, tenants, owners, and managers need
accurate information.
PMID- 25122027
TI - Effects of statewide job losses on adolescent suicide-related behaviors.
AB - OBJECTIVES: We investigated the impact of statewide job loss on adolescent
suicide-related behaviors. METHODS: We used 1997 to 2009 data from the Youth Risk
Behavior Survey and the Bureau of Labor Statistics to estimate the effects of
statewide job loss on adolescents' suicidal ideation, suicide attempts, and
suicide plans. Probit regression models controlled for demographic
characteristics, state of residence, and year; samples were divided according to
gender and race/ethnicity. RESULTS: Statewide job losses during the year
preceding the survey increased girls' probability of suicidal ideation and
suicide plans and non-Hispanic Black adolescents' probability of suicidal
ideation, suicide plans, and suicide attempts. Job losses among 1% of a state's
working-age population increased the probability of girls and Blacks reporting
suicide-related behaviors by 2 to 3 percentage points. Job losses did not affect
the suicide-related behaviors of boys, non-Hispanic Whites, or Hispanics. The
results were robust to the inclusion of other state economic characteristics.
CONCLUSIONS: As are adults, adolescents are affected by economic downturns. Our
findings show that statewide job loss increases adolescent girls' and non
Hispanic Blacks' suicide-related behaviors.
PMID- 25122029
TI - Adverse outcomes among homeless adolescents and young adults who report a history
of traumatic brain injury.
AB - OBJECTIVES: We examined the prevalence of self-reported traumatic brain injury
(TBI) among homeless young people and explored whether sociodemographic
characteristics, mental health diagnoses, substance use, exposure to violence, or
difficulties with activities of daily living (ADLs) were associated with TBI.
METHODS: We analyzed data from the Wilder Homelessness Study, in which
participants were recruited in 2006 and 2009 from streets, shelters, and
locations in Minnesota that provide services to homeless individuals.
Participants completed 30-minute interviews to collect information about history
of TBI, homelessness, health status, exposure to violence (e.g., childhood abuse,
assault), and other aspects of functioning. RESULTS: Of the 2732 participating
adolescents and young adults, 43% reported a history of TBI. Participants with
TBI became homeless at a younger age and were more likely to report mental health
diagnoses, substance use, suicidality, victimization, and difficulties with ADLs.
The majority of participants (51%) reported sustaining their first injury prior
to becoming homeless or at the same age of their first homeless episode (10%).
CONCLUSIONS: TBI occurs frequently among homeless young people and is a marker of
adverse outcomes such as mental health difficulties, suicidal behavior, substance
use, and victimization.
PMID- 25122028
TI - Enhancing diversity in the public health research workforce: the research and
mentorship program for future HIV vaccine scientists.
AB - OBJECTIVES: We developed and evaluated a novel National Institutes of Health
sponsored Research and Mentorship Program for African American and Hispanic
medical students embedded within the international, multisite HIV Vaccine Trials
Network, and explored its impact on scientific knowledge, acquired skills, and
future career plans. METHODS: Scholars conducted social, behavioral, clinical, or
laboratory-based research projects with HIV Vaccine Trials Network investigators
over 8 to 16 weeks (track 1) or 9 to 12 months (track 2). We conducted an in
depth, mixed-methods evaluation of the first 2 cohorts (2011-2013) to identify
program strengths, areas for improvement, and influence on professional
development. RESULTS: A pre-post program assessment demonstrated increases in
self-reported knowledge, professional skills, and interest in future HIV vaccine
research. During in-depth interviews, scholars reported that a supportive,
centrally administered program; available funding; and highly involved mentors
and staff were keys to the program's early success. CONCLUSIONS: A
multicomponent, mentored research experience that engages medical students from
underrepresented communities and is organized within a clinical trials network
may expand the pool of diverse public health scientists. Efforts to sustain
scholar interest over time and track career trajectories are warranted.
PMID- 25122030
TI - Analysis of the accuracy of weight loss information search engine results on the
internet.
AB - OBJECTIVES: We systematically identified and evaluated the quality and
comprehensiveness of online information related to weight loss that users were
likely to access. METHODS: We evaluated the content quality, accessibility of the
information, and author credentials for Web sites in 2012 that were identified
from weight loss specific queries that we generated. We scored the content with
respect to available evidence-based guidelines for weight loss. RESULTS: One
hundred three Web sites met our eligibility criteria (21 commercial, 52
news/media, 7 blogs, 14 medical, government, or university, and 9 unclassified
sites). The mean content quality score was 3.75 (range=0-16; SD=2.48).
Approximately 5% (4.85%) of the sites scored greater than 8 (of 12) on nutrition,
physical activity, and behavior. Content quality score varied significantly by
type of Web site; the medical, government, or university sites (mean=4.82,
SD=2.27) and blogs (mean=6.33, SD=1.99) had the highest scores. Commercial
(mean=2.37, SD=2.60) or news/media sites (mean=3.52, SD=2.31) had the lowest
scores (analysis of variance P<.005). CONCLUSIONS: The weight loss information
that people were likely to access online was often of substandard quality because
most comprehensive and quality Web sites ranked too low in search results.
PMID- 25122032
TI - On Agent Orange in Vietnam.
PMID- 25122031
TI - Impact of an exercise intervention on physical activity during pregnancy: the
behaviors affecting baby and you study.
AB - OBJECTIVES: We examined the impact of a prenatal exercise intervention on
physical activity in 260 women at risk for gestational diabetes mellitus.
METHODS: We randomized participants in the Behaviors Affecting Baby and You
(BABY) Study, which took place from 2007 to 2012, to either a 12-week
individually tailored, motivationally matched exercise intervention (n=132) or to
a comparison health and wellness intervention (n=128). We assessed physical
activity with the Pregnancy Physical Activity Questionnaire. We used linear mixed
models to evaluate the impact of the interventions on change in physical activity
according to intensity and type, total walking, and sedentary behavior. RESULTS:
Compared with the health and wellness arm, the exercise arm had significantly
greater increases in sports or exercise activity (0.3 vs 5.3 metabolic equivalent
of task [MET] hours/week; P<.001), and smaller declines in total activity (-42.7
vs -2.1 MET hours/week; P=.02) and activities of moderate to vigorous intensity (
30.6 vs -10.6 MET hours/week; P=.05), and was more likely to achieve recommended
guidelines for physical activity (odds ratio=2.12; 95% confidence interval=1.45,
3.10). CONCLUSIONS: These findings extend the previous literature by
demonstrating the benefits of a clinically feasible exercise intervention in an
ethnically and socio-economically diverse population. Given the increased risk of
adverse maternal health outcomes in ethnic minority groups, these findings may
have important implications for reducing health disparities.
PMID- 25122034
TI - Research informs abortion care policy change in California.
PMID- 25122035
TI - Reversibly tunable upconversion luminescence by host-guest chemistry.
AB - Tuning upconversion (UPC) luminescence using external stimuli and fields, as well
as chemical reactions, is expected to lead to novel and efficient optical
sensors. Herein, highly tunable UPC luminescence was achieved through a host
guest chemistry approach. Specifically, interlayer ion exchange reactions
reversibly tuned the emission intensity and green-red color of Er/Yb-codoped
A2La2Ti3O10 layered perovskite, where A corresponds to proton and alkali metal
ions, enabling the visualization of host-guest interactions and reactions.
PMID- 25122036
TI - Repair-dependent cell radiation survival and transformation: an integrated
theory.
AB - The repair-dependent model of cell radiation survival is extended to include
radiation-induced transformations. The probability of transformation is presumed
to scale with the number of potentially lethal damages that are repaired in a
surviving cell or the interactions of such damages. The theory predicts that at
doses corresponding to high survival, the transformation frequency is the sum of
simple polynomial functions of dose; linear, quadratic, etc, essentially as
described in widely used linear-quadratic expressions. At high doses,
corresponding to low survival, the ratio of transformed to surviving cells
asymptotically approaches an upper limit. The low dose fundamental- and high dose
plateau domains are separated by a downwardly concave transition region.
Published transformation data for mammalian cells show the high-dose plateaus
predicted by the repair-dependent model for both ultraviolet and ionizing
radiation. For the neoplastic transformation experiments that were analyzed, the
data can be fit with only the repair-dependent quadratic function. At low doses,
the transformation frequency is strictly quadratic, but becomes sigmodial over a
wider range of doses. Inclusion of data from the transition region in a
traditional linear-quadratic analysis of neoplastic transformation frequency data
can exaggerate the magnitude of, or create the appearance of, a linear component.
Quantitative analysis of survival and transformation data shows good agreement
for ultraviolet radiation; the shapes of the transformation components can be
predicted from survival data. For ionizing radiations, both neutrons and x-rays,
survival data overestimate the transforming ability for low to moderate doses.
The presumed cause of this difference is that, unlike UV photons, a single x-ray
or neutron may generate more than one lethal damage in a cell, so the
distribution of such damages in the population is not accurately described by
Poisson statistics. However, the complete sigmodial dose-response data for
neoplastic transformations can be fit using the repair-dependent functions with
all parameters determined only from transformation frequency data.
PMID- 25122033
TI - An education in contrast: state-by-state assessment of school immunization
records requirements.
AB - OBJECTIVES: We reviewed the complexities of school-related immunization policies,
their relation to immunization information systems (IIS) and immunization
registries, and the historical context to better understand this convoluted
policy system. METHODS: We used legal databases (Lexis-Nexis and Westlaw) to
identify school immunization records policies for 50 states, 5 cities, and the
District of Columbia (Centers for Disease Control and Prevention "grantees"). The
original search took place from May to September 2010 (cross-referenced in July
2013 with the list on http://www.immunize.org/laws ). We describe the
requirements, agreement with IIS policies, and penalties for policy violations.
RESULTS: We found a complex web of public health, medical, and education-directed
policies, which complicates immunization data sharing. Most (79%) require records
of immunizations for children to attend school or for a child-care institution
licensure, but only a few (11%) require coordination between IIS and schools or
child-care facilities. CONCLUSIONS: To realize the full benefit of IIS
investment, including improved immunization and school health program
efficiencies, IIS and school immunization records policies must be better
coordinated. States with well-integrated policies may serve as models for
effective harmonization.
PMID- 25122037
TI - Molecular xenomonitoring using mosquitoes to map lymphatic filariasis after mass
drug administration in American Samoa.
AB - BACKGROUND: Mass drug administration (MDA) programs have dramatically reduced
lymphatic filariasis (LF) incidence in many areas around the globe, including
American Samoa. As infection rates decline and MDA programs end, efficient and
sensitive methods for detecting infections are needed to monitor for
recrudescence. Molecular methods, collectively termed 'molecular xenomonitoring,'
can identify parasite DNA or RNA in human blood-feeding mosquitoes. We tested
mosquitoes trapped throughout the inhabited islands of American Samoa to identify
areas of possible continuing LF transmission after completion of MDA.
METHODOLOGY/PRINCIPLE FINDINGS: Mosquitoes were collected using BG Sentinel traps
from most of the villages on American Samoa's largest island, Tutuila, and all
major villages on the smaller islands of Aunu'u, Ofu, Olosega, and Ta'u. Real
time PCR was used to detect Wuchereria bancrofti DNA in pools of <= 20
mosquitoes, and PoolScreen software was used to infer territory-wide prevalences
of W. bancrofti DNA in the mosquitoes. Wuchereria bancrofti DNA was found in
mosquitoes from 16 out of the 27 village areas sampled on Tutuila and Aunu'u
islands but none of the five villages on the Manu'a islands of Ofu, Olosega, and
Ta'u. The overall 95% confidence interval estimate for W. bancrofti DNA
prevalence in the LF vector Ae. polynesiensis was 0.20-0.39%, and parasite DNA
was also detected in pools of Culex quinquefasciatus, Aedes aegypti, and Aedes
(Finlaya) spp. CONCLUSIONS/SIGNIFICANCE: Our results suggest low but widespread
prevalence of LF on Tutuila and Aunu'u where 98% of the population resides, but
not Ofu, Olosega, and Ta'u islands. Molecular xenomonitoring can help identify
areas of possible LF transmission, but its use in the LF elimination program in
American Samoa is limited by the need for more efficient mosquito collection
methods and a better understanding of the relationship between prevalence of W.
bancrofti DNA in mosquitoes and infection and transmission rates in humans.
PMID- 25122038
TI - Hippocampal volume and the rapid antidepressant effect of ketamine.
AB - Accumulating evidence underscores the utility of ketamine in treating severely
treatment-resistant depressed patients. We investigated the relationship between
the rapid antidepressant effects of ketamine and hippocampal volume, a biomarker
of antidepressant treatment outcome. We gave 16 medication-free, major depressive
disorder (MDD) patients a single, sub-anesthetic dose infusion of ketamine (0.5
mg/kg, over 40 min). We assessed depression severity pre-treatment, and at 24 h
post-treatment, with the Montgomery-Asberg Depression Rating Scale (MADRS). Prior
to treatment, patients underwent magnetic resonance imaging (MRI) to estimate
their hippocampal volume: We obtained viable MRI data in 13 patients. Delta MADRS
(post- minus pre-treatment) was significantly correlated with the pre-treatment
volumes of the left hippocampus (r = 0.66; p = 0.01), but not the right
hippocampus (r = 0.49; p = 0.09). The correlation between delta MADRS and the
left hippocampus remained high (r > 0.6; p = 0.13), after controlling for several
demographic and clinical variables, although the p value increased due to the
reduced degree of freedom (df = 5). Ketamine exerts enhanced antidepressant
effects in patients with a relatively smaller hippocampus, a patient population
that has been repeatedly shown to be refractory to traditional antidepressants.
PMID- 25122039
TI - Analysis of sociability and preference for social novelty in the acute and
subchronic phencyclidine rat.
AB - Both acute and sub-chronic phencyclidine administration produce behavioural and
pathophysiological changes that resemble some features of schizophrenia. The
present study aimed to determine if acute and sub-chronic phencyclidine treatment
in male rats produces deficits in sociability and social novelty preference,
which may reflect aspects of the negative symptomatology observed in
schizophrenia. Rats were treated with phencyclidine acutely (2 or 5 mg/kg) or
subchronically (2 or 5 mg/kg bi-daily for one week followed by a one week wash
out period) or vehicle. Social affiliative behaviour was assessed using the
sociability and preference for social novelty paradigm where social interaction
time was measured in (a) a chamber containing an unfamiliar conspecific vs an
empty chamber (sociability), or (b) a chamber containing an unfamiliar
conspecific vs a chamber containing a familiar conspecific (preference for social
novelty). Results showed that acute administration of phencyclidine produced a
reduction in measures of sociability but had no effect on preference for social
novelty while sub-chronic administration of phencyclidine had no effect on
sociability or social novelty. This study provides further evidence for the
usefulness of phencyclidine models in modelling the symptomatology of
schizophrenia.
PMID- 25122040
TI - Effects of tobacco smoke constituents, anabasine and anatabine, on memory and
attention in female rats.
AB - Nicotine has been well characterized to improve memory and attention. Nicotine is
the primary, but not only neuroactive compound in tobacco. Other tobacco
constituents such as anabasine and anatabine also have agonist actions on
nicotinic receptors. The current study investigated the effects of anabasine and
anatabine on memory and attention. Adult female Sprague-Dawley rats were trained
on a win-shift spatial working and reference memory task in the 16-arm radial
maze or a visual signal detection operant task to test attention. Acute dose
effect functions of anabasine and anatabine over two orders of magnitude were
evaluated for both tasks. In the radial-arm maze memory test, anabasine but not
anatabine significantly reduced the memory impairment caused by the NMDA
antagonist dizocilpine (MK-801). In the signal detection attentional task,
anatabine but not anabasine significantly attenuated the attentional impairment
caused by dizocilpine. These studies show that non-nicotine nicotinic agonists in
tobacco, similar to nicotine, can significantly improve memory and attentional
function. Both anabasine and anatabine produced cognitive improvement, but their
effectiveness differed with regard to memory and attention. Follow-up studies
with anabasine and anatabine are called for to determine their efficacy as
therapeutics for memory and attentional dysfunction.
PMID- 25122041
TI - Central noradrenergic mechanisms and the acute stress response during painful
stimulation.
AB - Events that threaten tissue integrity including noxious stimulation activate
central noradrenergic circuits, particularly locus coeruleus and its projections.
Recent advances in theory hold that an adaptive, defensive shift in brain
activity takes place in response to threat. In principle, this shift may
accentuate the autonomic and central biomarkers of the perception of painful
events and the experience of pain itself. We have examined the effects of an
alpha-2 agonist on pupil dilation responses, skin conductance responses, near
field somatosensory evoked potentials and pain reports in normal volunteers
undergoing repeated trials of painful fingertip stimulation delivered at low,
medium and high intensities. In a double-blinded study, 114 healthy male and
female volunteers underwent repeated noxious stimulation under baseline, placebo
and active drug conditions where the active drug was the alpha-2 agonist
tizanidine 4 mg. In contrast to baseline and placebo conditions, tizanidine 4 mg
significantly reduced the magnitudes of the mean pupil dilation response, the
mean skin conductance response, the mean near field somatosensory evoked
potential peak-to-peak amplitude and the mean pain intensity rating. Stimulus
intensity significantly altered all three biomarkers and the pain report in a
graded fashion. There were no sex differences. These findings support the
hypotheses that painful events activate central noradrenergic circuits, and that
these circuits play a role in the autonomic and central arousal associated with
pain.
PMID- 25122042
TI - Potentiation of latent inhibition by haloperidol and clozapine is attenuated in
Dopamine D2 receptor (Drd-2)-deficient mice: do antipsychotics influence learning
to ignore irrelevant stimuli via both Drd-2 and non-Drd-2 mechanisms?
AB - Whether the dopamine Drd-2 receptor is necessary for the behavioural action of
antipsychotic drugs is an important question, as Drd-2 antagonism is responsible
for their debilitating motor side effects. Using Drd-2 null mice (Drd2 -/-) it
has previously been shown that Drd-2 is not necessary for antipsychotic drugs to
reverse D-amphetamine disruption of latent inhibition (LI), a behavioural measure
of learning to ignore irrelevant stimuli. Weiner's 'two-headed' model indicates
that antipsychotics not only reverse LI disruption, 'disrupted LI', but also
potentiate LI when low/absent in controls, 'persistent' LI. We investigated
whether antipsychotic drugs haloperidol or clozapine potentiated LI in wild-type
controls or Drd2 -/-. Both drugs potentiated LI in wild-type but not in Drd2 -/-
mice, suggesting moderation of this effect of antipsychotics in the absence of
Drd-2. Haloperidol potentiated LI similarly in both Drd1 -/- and wild-type mice,
indicating no such moderation in Drd1 -/-. These data suggest that antipsychotic
drugs can have either Drd-2 or non-Drd-2 effects on learning to ignore irrelevant
stimuli, depending on how the abnormality is produced. Identification of the non
Drd-2 mechanism may help to identify novel non-Drd2 based therapeutic strategies
for psychosis.
PMID- 25122045
TI - Electrophysiological correlates of alcohol- and non-alcohol-related stimuli
processing in binge drinkers: a follow-up study.
AB - BACKGROUND: The continuation of binge drinking is associated with the development
of neurocognitive brain abnormalities similar to those observed in patients with
alcohol dependence. Alcohol cue reactivity constitutes a risk marker for alcohol
dependence. Through event-related potentials (ERPs), we aimed to examine its
potential presence as well as its evolution over time in binge drinkers in a one
year period. METHODS: ERPs were recorded during a visual oddball task in which
controls (n=15) and binge drinkers (n=15) had to detect infrequent deviant
stimuli (related or unrelated to alcohol) among frequent standard stimuli. The
test was performed twice with a one-year interval in order to explore the long
lasting influence of drinking habits. RESULTS: Contrary to the controls, binge
drinkers showed significantly reduced amplitudes of the P1 component for both
alcohol and non-alcohol-related cues and of the P3 component only for neutral
cues in the second assessment compared with the first. CONCLUSION: The
continuation of binge drinking over one year is associated with the development
of brain functional abnormalities (indexed by the P1 component) as well as a
higher reactivity to alcohol-related stimuli and/or a decreased reactivity to non
alcohol-related stimuli (indexed by the P3 component).
PMID- 25122043
TI - Vortioxetine disinhibits pyramidal cell function and enhances synaptic plasticity
in the rat hippocampus.
AB - Vortioxetine, a novel antidepressant with multimodal action, is a serotonin (5
HT)3, 5-HT7 and 5-HT1D receptor antagonist, a 5-HT1B receptor partial agonist, a
5-HT1A receptor agonist and a 5-HT transporter (SERT) inhibitor. Vortioxetine has
been shown to improve cognitive performance in several preclinical rat models and
in patients with major depressive disorder. Here we investigated the mechanistic
basis for these effects by studying the effect of vortioxetine on synaptic
transmission, long-term potentiation (LTP), a cellular correlate of learning and
memory, and theta oscillations in the rat hippocampus and frontal cortex.
Vortioxetine was found to prevent the 5-HT-induced increase in inhibitory post
synaptic potentials recorded from CA1 pyramidal cells, most likely by 5-HT3
receptor antagonism. Vortioxetine also enhanced LTP in the CA1 region of the
hippocampus. Finally, vortioxetine increased fronto-cortical theta power during
active wake in whole animal electroencephalographic recordings. In comparison,
the selective SERT inhibitor escitalopram showed no effect on any of these
measures. Taken together, our results indicate that vortioxetine can increase
pyramidal cell output, which leads to enhanced synaptic plasticity in the
hippocampus. Given the central role of the hippocampus in cognition, these
findings may provide a cellular correlate to the observed preclinical and
clinical cognition-enhancing effects of vortioxetine.
PMID- 25122044
TI - Effects of ecstasy on cooperative behaviour and perception of trustworthiness: a
naturalistic study.
AB - BACKGROUND: Acute recreational use of 3,4-methylenedioxymethamphetamine (MDMA;
'ecstasy') can promote pro-social effects which may alter interpersonal
perceptions. AIMS: To explore such effects, this study investigated whether acute
recreational use of ecstasy was associated with changes in individual perception
of trustworthiness of people's faces and co-operative behaviours. METHOD: An
independent group, repeated measures design was used in which 17 ecstasy users
were tested on the night of drug use (day 0) and again three days later (day 3);
22 controls were tested on parallel days. On each day, participants rated the
trustworthiness of 66 faces, carried out three co-operative behaviour tasks
(public good; dictator; ultimatum game) and completed mood self-ratings. RESULTS:
Acute ecstasy use was associated with increased face trustworthiness ratings and
increased cooperative behaviour on the dictator and ultimatum games; on day 3
there were no group differences on any task. Self-ratings showed the standard
acute ecstasy effects (euphoria, energy, jaw clenching) with negative effects
(less empathy, compassion, more distrust, hostility) emerging on day 3.
CONCLUSIONS: Our findings of increased perceived trustworthiness and co-operative
behaviours following use of ecstasy suggest that a single dose of the drug
enhances aspects of empathy. This may in turn contribute to its popularity as a
recreational drug and potentially to its enhancement of the therapeutic alliance
in psychotherapy.
PMID- 25122046
TI - CYP2C19 variation, not citalopram dose nor serum level, is associated with QTc
prolongation.
AB - Recently, a FDA Safety Communication warned of a dose-dependent risk for QTc
prolongation with citalopram, which is metabolized by CYP2C19 of the cytochrome
P450 system. We investigate associations between citalopram and escitalopram
dose, serum concentration, CYP2C19 phenotype, and QTc. We undertook a
retrospective chart review of citalopram or escitalopram patients with the
inclusion criteria of consistent medication dose, CYP2C19 phenotype (extensive
metabolizers [EM], intermediate metabolizers [IM], poor metabolizers [PM]), and
QTc interval on ECG. We further identified 42 citalopram users with citalopram
serum concentration measurements and ECG. Regression and one-way ANOVA were used
to examine the relationship between citalopram dose, citalopram serum
concentration, CYP2C19 phenotype, and QTc interval. Of 75 citalopram patients,
the EM group had significantly shorter QTc intervals than a combined IM+PM group
(427.1+/-23.6 ms vs. 440.1+/-26.6 ms, one-tailed t-test, p=0.029). In the 80
escitalopram cohort, there was no significant difference in QTc between phenotype
groups. There was no statistical correlation between citalopram (p=0.62) or
escitalopram (p=0.30) dose and QTc. QTc was not associated with citalopram serum
level (p=0.45). In contrast to the FDA warning, this study found no association
between citalopram/escitalopram dose and QTc. However, PM of the drug tended to
have longer QTc intervals. Our findings suggest cytochrome P450 genotyping in
select patients may be helpful to guide medication optimization while limiting
harmful effects.
PMID- 25122047
TI - A radical approach to balancing the tides of tubular flow.
PMID- 25122049
TI - Angiotensin induces a pressor regulating role for collecting duct renin.
PMID- 25122048
TI - Collecting duct-specific knockout of renin attenuates angiotensin II-induced
hypertension.
AB - The physiological and pathophysiological significance of collecting duct (CD)
derived renin, particularly as it relates to blood pressure (BP) regulation, is
unknown. To address this question, we generated CD-specific renin knockout (KO)
mice and examined BP and renal salt and water excretion. Mice containing loxP
flanked exon 1 of the renin gene were crossed with mice transgenic for aquaporin
2-Cre recombinase to achieve CD-specific renin KO. Compared with controls, CD
renin KO mice had 70% lower medullary renin mRNA and 90% lower renin mRNA in
microdissected cortical CD. Urinary renin levels were significantly lower in KO
mice (45% of control levels) while plasma renin concentration was significantly
higher in KO mice (63% higher than controls) during normal-Na intake. While no
observable differences were noted in BP between the two groups with varying Na
intake, infusion of angiotensin II at 400 ng.kg(-1).min(-1) resulted in an
attenuated hypertensive response in the KO mice (mean arterial pressure 111 +/- 4
mmHg in KO vs. 128 +/- 3 mmHg in controls). Urinary renin excretion and
epithelial Na(+) channel (ENaC) remained significantly lower in the KO mice
following ANG II infusion compared with controls. Furthermore, membrane
associated ENaC protein levels were significantly lower in KO mice following ANG
II infusion. These findings suggest that CD renin modulates BP in ANG II-infused
hypertension and these effects are associated with changes in ENaC expression.
PMID- 25122051
TI - WHO gives go ahead for experimental treatments to be used in Ebola outbreak.
PMID- 25122050
TI - Oxidative stress-induced alterations in PPAR-gamma and associated mitochondrial
destabilization contribute to kidney cell apoptosis.
AB - The mechanism(s) underlying renoprotection by peroxisome proliferator-activated
receptor (PPAR)-gamma agonists in diabetic and nondiabetic kidney disease are not
well understood. Mitochondrial dysfunction and oxidative stress contribute to
kidney disease. PPAR-gamma upregulates proteins required for mitochondrial
biogenesis. Our aim was to determine whether PPAR-gamma has a role in protecting
the kidney proximal tubular epithelium (PTE) against mitochondrial
destabilisation and oxidative stress. HK-2 PTE cells were subjected to oxidative
stress (0.2-1.0 mM H2O2) for 2 and 18 h and compared with untreated cells for
apoptosis, mitosis (morphology/biomarkers), cell viability (MTT), superoxide
(dihydroethidium), mitochondrial function (MitoTracker red and JC-1), ATP
(luminescence), and mitochondrial ultrastructure. PPAR-gamma, phospho-PPAR-gamma,
PPAR-gamma coactivator (PGC)-1alpha, Parkin (Park2), p62, and light chain
(LC)3beta were investigated using Western blots. PPAR-gamma was modulated using
the agonists rosiglitazone, pioglitazone, and troglitazone. Mitochondrial
destabilization increased with H2O2concentration, ATP decreased (2 and 18 h; P <
0.05), Mitotracker red and JC-1 fluorescence indicated loss of mitochondrial
membrane potential, and superoxide increased (18 h, P < 0.05). Electron
microscopy indicated sparse mitochondria, with disrupted cristae. Mitophagy was
evident at 2 h (Park2 and LC3beta increased; p62 decreased). Impaired mitophagy
was indicated by p62 accumulation at 18 h (P < 0.05). PPAR-gamma expression
decreased, phospho-PPAR-gamma increased, and PGC-1alpha decreased (2 h),
indicating aberrant PPAR-gamma activation and reduced mitochondrial biogenesis.
Cell viability decreased (2 and 18 h, P < 0.05). PPAR-gamma agonists promoted
further apoptosis. In summary, oxidative stress promoted mitochondrial
destabilisation in kidney PTE, in association with increased PPAR-gamma
phosphorylation. PPAR-gamma agonists failed to protect PTE. Despite positive
effects in other tissues, PPAR-gamma activation appears to be detrimental to
kidney PTE health when oxidative stress induces damage.
PMID- 25122053
TI - Whole exome sequencing implicates an INO80D mutation in a syndrome of aortic
hypoplasia, premature atherosclerosis, and arterial stiffness.
AB - BACKGROUND: Massively parallel, high-throughput sequencing technology is helping
to generate new insights into the genetic basis of human diseases. We used whole
exome sequencing to identify the mutation underlying a syndrome affecting 2
siblings with aortic hypoplasia, calcific atherosclerosis, systolic hypertension,
and premature cataract. METHODS AND RESULTS: Exonic regions were captured and
sequenced using a next-generation sequencing platform to generate 100 bases
paired-end reads. A computational genomic data analysis pipeline was used to
perform quality control, align reads to a reference genome, and identify genetic
variants; findings were confirmed using a different exome analyses pipeline. The
2 siblings were homozygous for a rare missense mutation (Ser818Cys) in INO80D, a
subunit of the human INO80 chromatin remodeling complex. Homozygosity mapping and
Sanger sequencing confirmed that the mutation is located in one of the runs of
homozygosity on chromosome 2. INO80D encodes a key subunit of the human IN080
complex, a multiprotein complex involved in DNA binding, chromatin modification,
organization of chromosome structure, and ATP-dependent nucleosome sliding. By
introducing a new disulphide-bond in the protein product and also disrupting the
composition of low-complexity regions, the Ser818Cys mutation may affect INO80D
function, protein-protein interactions, and chromatin remodeling. CONCLUSIONS:
Our findings suggest a link between the Ser818Cys mutation in INO80D, a subunit
of the human INO80 chromatin remodeling complex, and accelerated arterial aging.
PMID- 25122052
TI - Low-expression variant of fatty acid-binding protein 4 favors reduced
manifestations of atherosclerotic disease and increased plaque stability.
AB - BACKGROUND: Fatty acid-binding protein 4 (FABP4 or aP2 in mice) has been
identified as a key regulator of core aspects of cardiometabolic disorders,
including lipotoxic endoplasmic reticulum stress in macrophages. A functional
promoter polymorphism (rs77878271) of human FABP4 gene has been described
resulting in reduced FABP4 transcription. METHODS AND RESULTS: We investigated
the effects of this low-expression variant of FABP4 on cardiovascular morbidity
and carotid atherosclerosis on a population level (n=7491) and in patient cohorts
representing endarterectomized patients with advanced carotid atherosclerosis
(n=92) and myocardial infarction (n=3432). We found that the low-expression
variant was associated with decreased total cholesterol levels (P=0.006) with the
largest reduction in variant allele homozygotes. Obese variant allele carriers
also showed reduced carotid intima-media thickness (P=0.010) and lower prevalence
of carotid plaques (P=0.060). Consistently, the variant allele homozygotes showed
8-fold lower odds for myocardial infarction (P=0.019; odds ratio, 0.12; 95%
confidence interval, 0.003-0.801). Within the carotid plaques, the variant allele
was associated with a 3.8-fold reduction in FABP4 transcription (P=0.049) and 2.7
fold reduction in apoptosis (activated caspase 3; P=0.043). Furthermore, the
variant allele was enriched to patients with asymptomatic carotid stenosis
(P=0.038). High FABP4 expression in the carotid plaques was associated with lipid
accumulation, intraplaque hemorrhages, plaque ulcerations, and phosphoactivated
endoplasmic reticulum stress markers. CONCLUSIONS: Our results reveal FABP4
rs77878271 as a novel variant affecting serum total cholesterol levels and
cardiovascular risk. A therapeutic regimen reducing FABP4 expression within the
atherosclerotic plaque may promote lesion stability through modulation of
endoplasmic reticulum stress signaling, and attenuation of apoptosis, lipid
burden, and inflammation.
PMID- 25122056
TI - Nurses' use of an integrated electronic health record: results of a case site
analysis.
AB - Purpose: To explore how nurses use an integrated Electronic Health Record (EHR)
in practice. Methods: A multi-site case study across two hospitals in Kaiser
Permanente Northern California. Non-participant observation was used to explore
nurses' use of the EHR, while semi-structured interviews with nurses and managers
explored their perceptions of the EHR and how it affected their practice. Data
were analyzed thematically using codes derived deductively from the literature
and inductively from the data. Results: Key themes arising from the analysis
suggest that the EHR changed various elements of the way nurses practiced.
Introducing the EHR was thought to have improved communication, ease of access to
information and the safety of medication administration processes. At an
organizational level, there was variability in how the EHR was used to support
care documentation and initiatives to improve the quality of care provided by
nurses. Conclusion: The EHR was perceived to improve efficiency, safety and
communication by the majority of nurses who were interviewed. However, it is
likely that a number of other factors such as individual nurse's characteristics
and organizational culture influence how an EHR can be used effectively to
improve outcomes for patients.
PMID- 25122054
TI - Volatilization of arsenic from polluted soil by Pseudomonas putida engineered for
expression of the arsM Arsenic(III) S-adenosine methyltransferase gene.
AB - Even though arsenic is one of the most widespread environmental carcinogens,
methods of remediation are still limited. In this report we demonstrate that a
strain of Pseudomonas putida KT2440 endowed with chromosomal expression of the
arsM gene encoding the As(III) S-adenosylmethionine (SAM) methyltransfase from
Rhodopseudomonas palustris to remove arsenic from contaminated soil. We
genetically engineered the P. putida KT2440 with stable expression of an arsM-gfp
fusion gene (GE P. putida), which was inserted into the bacterial chromosome. GE
P. putida showed high arsenic methylation and volatilization activity. When
exposed to 25 MUM arsenite or arsenate overnight, most inorganic arsenic was
methylated to the less toxic methylated arsenicals methylarsenate (MAs(V)),
dimethylarsenate (DMAs(V)) and trimethylarsine oxide (TMAs(V)O). Of total added
arsenic, the species were about 62 +/- 2.2% DMAs(V), 25 +/- 1.4% MAs(V) and 10 +/
1.2% TMAs(V)O. Volatilized arsenicals were trapped, and the predominant species
were dimethylarsine (Me2AsH) (21 +/- 1.0%) and trimethylarsine (TMAs(III)) (10 +/
1.2%). At later times, more DMAs(V) and volatile species were produced.
Volatilization of Me2AsH and TMAs(III) from contaminated soil is thus possible
with this genetically engineered bacterium and could be instrumental as an agent
for reducing the inorganic arsenic content of soil and agricultural products.
PMID- 25122055
TI - Changes in the expression of cyp35a family genes in the soil nematode
Caenorhabditis elegans under controlled exposure to chlorpyrifos using passive
dosing.
AB - In order to use sensitive molecular-level biomarkers for the evaluation of
environmental risks, it is necessary to establish a quantitative dose-response
relationship. Passive dosing is regarded as a promising new technique for
maintaining a constant exposure condition of hydrophobic chemicals in the assay
medium. The main goals of the present study were (1) to quantitatively compare
gene expression results obtained using the passive dosing method and the
conventional spiking method and (2) to investigate changes in gene expression
with respect to the free concentration and exposure duration using passive
dosing. Chlorpyrifos (CP), which is oxidized by the cytochrome P450
monooxygenases, was selected as a model chemical, and the expression of
cytochrome P450 subfamily protein 35A gene series (cyp-35a1-5) was analyzed by
quantitative real-time PCR on soil nematode Caenorhabditis elegans. Whereas the
free concentration of CP rapidly decreased and the expression of cyp genes varied
with the volume of exposure medium and the test duration when the spiking method
was used, the free concentration in the assay medium was stable throughout the
experiment when the passive dosing method was used. In addition, the level of
gene expression increased with exposure time up to 8 h and with increasing CP
concentration. The observed increased gene expression could be explained by
increasing body residue concentration of CP with exposure time. In conclusion,
quantitative dose-response relationships for gene expression biomarkers could be
obtained for highly hydrophobic chemicals when the constant exposure condition is
provided and the free concentration is used as the dose-metric.
PMID- 25122058
TI - Targeted MRSA screening can be as effective as universal screening.
PMID- 25122057
TI - Effect of FGF-2 on collagen tissue regeneration by human vertebral bone marrow
stem cells.
AB - The effects of fibroblast growth factor-2 (FGF-2) on collagen tissue regeneration
by human bone marrow stem cells (hBMSCs) were investigated. hBMSCs were isolated
from human vertebral body bone marrow during vertebral surgery and a population
of hBMSCs with the characteristics of mesenchymal stem cells was observed. The
FGF-2 treatment (5 ng/mL) affected on the colony-forming efficiency,
proliferation, and in vitro differentiation of hBMSCs. Insoluble/soluble collagen
and hydroxyproline synthesis was significantly enhanced in hBMSCs expanded with
FGF-2 and the treatment of FGF-2 caused a reduction in the mRNA expression of
collagen type I, but an increase of collagen types II and III along with lysyl
oxidase family genes. Collagen formation was also examined using an in vivo assay
model by transplanting hBMSCs into immunocompromised mice (n=4) and the
histologic and immunohistochemical results revealed that significantly more
collagen with a well-organized structure was formed by FGF-2-treated hBMSCs at 8
weeks posttransplantation (P<0.05). The DNA microarray assay demonstrated that
genes related to extracellular matrix formation were significantly upregulated.
To elucidate the underlying mechanism, chemical inhibitors against extracellular
signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K) were treated
and following downstream expression was observed. Collectively, FGF-2 facilitated
the collagen-producing potency of hBMSCs both in vitro and in vivo, rendering
them more suitable for use in collagen regeneration in the clinical field.
PMID- 25122060
TI - Dramatic changes in 67 miRNAs during initiation of first wave of spermatogenesis
in Mus musculus testis: global regulatory insights generated by miRNA-mRNA
network analysis.
AB - We mapped global changes in miRNA and mRNA profiles spanning the first wave of
spermatogenesis using prepubertal (Postnatal Day 8 [P8]), pubertal (P16), and
adolescent (P24) Mus musculus testes and identified the differential expression
of 67 miRNAs and 8226 mRNAs. These two data sets were integrated into miRNA
dependent regulatory networks based on miRWalk predictions. In a network
representing the P8 to P16 transition, downregulation of four miRNAs and
upregulation of 19 miRNAs were linked with 81 upregulated target mRNAs and 228
downregulated target mRNAs, respectively. Furthermore, during the P16 to P24
transition, two miRNAs were downregulated, and eight miRNAs were upregulated,
which linked with 64 upregulated mRNAs and 389 downregulated mRNAs, respectively.
Only three of the miRNAs present in the network (miR-34b-5p, miR-34c, and miR
449a) showed a progressive increase from P8 through P16 to P24, while the
remaining miRNAs in the network showed statistically significant changes in their
levels either during the P8 to P16 transition or during the P16 to P24
transition. Analysis of the chromosomal location of these differentially
expressed miRNAs showed that 14 out of 25 miRNAs upregulated from P8 to P16, and
18 out of 40 miRNAs upregulated from P8 to P24 were X-linked. This is suggestive
of their escape from meiotic sex chromosome inactivation and postmeiotic sex
chromatin. This integrated network of miRNA-level and mRNA-level changes in mouse
testis during the first wave of spermatogenesis is expected to build a base for
evaluating the role of miRNA-mediated gene expression regulation in maturing
mammalian testis.
PMID- 25122061
TI - Trophoblast-specific reduction of VEGFA alters placental gene expression and
maternal cardiovascular function in mice.
AB - Given the angiogenic function of vascular endothelial growth factor A (VEGFA),
the function of its expression by trophoblast in the avascular placental
junctional zone is unknown. In mice, cells from the trophoblast-specific protein
alpha (Tpbpa) lineage populate this zone and, in late gestation, some of these
cells invade the decidual layer. To diminish Vegfa expression in Tpbpa cells, we
crossed Vegfa(flox/flox) females with males carrying Tpbpa-Cre. For single
deletion (sd) of Vegfa in Tpbpa cells in 100% of conceptuses (SD100 pregnancies,
sd conceptuses) we crossed homozygous lines. For double deletion (dd) of both
Vegfa alleles in 50% of the conceptuses (DD50 pregnancies, 50% dd conceptuses and
50% no deletion [nd]), we crossed homozygous Vegfa(flox/flox) females with males
heterozygous for Tpbpa-Cre and homozygous for Vegfa(flox/flox). Controls were
Vegfa(flox/flox) females bred to wild-type males (V-CTRL pregnancies). In SD100
pregnancies, maternal plasma immunoreactive VEGFA significantly increased and
arterial blood pressure decreased, whereas fetal body weight and placental Flt1,
sFlt1, and Prl3b1 mRNA were unchanged. In DD50, maternal immunoreactive VEGFA and
arterial pressures were unaltered, but both dd and nd conceptuses exhibited
significantly increased embryonic lethality, altered expression of Flt1, sFlt1,
and Prl3b1 mRNA in the decidual layer, and decreased fetal body weight relative
to V-CTRL. Maternal cardiac output significantly increased in proportion to dd
conceptuses in the pregnancy. In DD50, results are consistent with altered
maternal function beginning in early gestation and adversely impacting both
conceptus genotypes. We conclude that maternal function is influenced by Vegfa
expression in trophoblast cells at the maternal-fetal interface, likely via an
endocrine mechanism.
PMID- 25122062
TI - MicroRNA-378a-5p targets cyclin G2 to inhibit fusion and differentiation in BeWo
cells.
AB - MicroRNAs are expressed abundantly in the placenta throughout pregnancy. We have
previously reported that microRNA (miR)-378a-5p promoted trophoblast migration
and invasion. To further understand the role of miR-378a-5p during placental
development, we investigated whether it may regulate the differentiation of
syncytiotrophoblast (STB). Using a choriocarcinoma cell line, BeWo, we found that
miR-378a-5p was down-regulated during forskolin-induced STB differentiation.
Transfection of a miR-378a-5p mimic into BeWo cells decreased the formation of
multinucleated STB, increased E-cadherin, and decreased the expression level of
STB marker genes. On the other hand, transfection of anti-miR-378a-5p resulted in
an increase in formation of multinucleated STB and expression of STB marker
genes, as well as the loss of E-cadherin. Bioinformatic analysis revealed that
miR-378a-5p has four potential binding sites at the 3' untranslated region (UTR)
of cyclin G2 (CCNG2). Using luciferase reporter assays, we showed that miR-378a
5p decreased the luciferase activity of reporter constructs that contain CCNG2 3'
UTR. In addition, miR-378a-5p decreased, whereas anti-miR-378a-5p increased,
CCNG2 mRNA levels. Overexpression of CCNG2 increased the expression of syncytin-1
and fusion index and reversed the inhibitory effects of miR-378a-5p. In contrast,
silencing of CCNG2 using siRNA increased E-cadherin and decreased syncytin-1
levels. These findings provide initial evidence that CCNG2 promotes STB
differentiation and suggest that miR-378a-5p exerts an inhibitory role in STB
differentiation, in part, by down-regulating CCNG2 expression, in the BeWo cell
model.
PMID- 25122063
TI - Endocrine gland-derived endothelial growth factor (EG-VEGF) is a potential novel
regulator of human parturition.
AB - EG-VEGF is an angiogenic factor that we identified as a new placental growth
factor during human pregnancy. EG-VEGF is also expressed in the mouse fetal
membrane (FM) by the end of gestation, suggesting a local role for this protein
in the mechanism of parturition. However, injection of EG-VEGF to gravid mice did
not induce labor, suggesting a different role for EG-VEGF in parturition. Here,
we searched for its role in the FM in relation to human parturition. Human
pregnant sera and total FM, chorion, and amnion were collected during the second
and third trimesters from preterm no labor, term no labor, and term labor
patients. Primary human chorion trophoblast and FM explants cultures were also
used. We demonstrate that circulating EG-VEGF increased toward term and
significantly decreased at the time of labor. EG-VEGF production was higher in
the FM compared to placentas matched for gestational age. Within the FM, the
chorion was the main source of EG-VEGF. EG-VEGF receptors, PROKR1 and PROKR2,
were differentially expressed within the FM with increased expression toward term
and an abrupt decrease with the onset of labor. In chorion trophoblast and FM
explants collected from nonlaboring patients, EG-VEGF decreased metalloproteinase
2 and -9 activities and increased PGDH (prostaglandin-metabolizing enzyme)
expression. Altogether these data demonstrate that EG-VEGF is a new cytokine that
acts locally to ensure FM protection in late pregnancy. Its fine contribution to
the initiation of human labor is exhibited by the abrupt decrease in its levels
as well as a reduction in its receptors.
PMID- 25122064
TI - The role of placental nutrient sensing in maternal-fetal resource allocation.
AB - The placenta mediates maternal-fetal exchange and has historically been regarded
as a passive conduit for nutrients. However, emerging evidence suggests that the
placenta actively responds to nutritional and metabolic signals from the mother
and the fetus. We propose that the placenta integrates a multitude of maternal
and fetal nutritional cues with information from intrinsic nutrient-sensing
signaling pathways to match fetal demand with maternal supply by regulating
maternal physiology, placental growth, and nutrient transport. This process,
which we have called placental nutrient sensing, ensures optimal allocation of
resources between the mother and the fetus to maximize the chances for
propagation of parental genes without jeopardizing maternal health. We suggest
that these mechanisms have evolved because of the evolutionary pressures of
maternal undernutrition, which result in decreased placental growth and down
regulation of nutrient transporters, thereby limiting fetal growth to ensure
maternal survival. These regulatory loops may also function in response to
maternal overnutrition, leading to increased placental growth and nutrient
transport in cases of maternal obesity or gestational diabetes. Thus, placental
nutrient sensing modulates maternal-fetal resource allocation to increase the
likelihood of reproductive success. This model implies that the placenta plays a
critical role in mediating fetal programming and determining lifelong health.
PMID- 25122066
TI - Synergistic simvastatin and metformin combination chemotherapy for osseous
metastatic castration-resistant prostate cancer.
AB - Docetaxel chemotherapy remains a standard of care for metastatic castration
resistant prostate cancer (CRPC). Docetaxel modestly increases survival, yet
results in frequent occurrence of side effects and resistant disease. An
alternate chemotherapy with greater efficacy and minimal side effects is needed.
Acquisition of metabolic aberrations promoting increased survival and metastasis
in CRPC cells includes constitutive activation of Akt, loss of adenosine
monophosphate-activated protein kinase (AMPK) activity due to Ser-485/491
phosphorylation, and overexpression of 3-hydroxy-3-methylglutaryl-Coenzyme A
reductase (HMG-CoAR). We report that combination of simvastatin and metformin,
within pharmacologic dose range (500 nmol/L to 4 MUmol/L simvastatin and 250
MUmol/L to 2 mmol/L metformin), significantly and synergistically reduces C4
2B3/B4 CRPC cell viability and metastatic properties, with minimal adverse
effects on normal prostate epithelial cells. Combination of simvastatin and
metformin decreased Akt Ser-473 and Thr-308 phosphorylation and AMPKalpha Ser
485/491 phosphorylation; increased Thr-172 phosphorylation and AMPKalpha
activity, as assessed by increased Ser-79 and Ser-872 phosphorylation of acetyl
CoA carboxylase and HMG-CoAR, respectively; decreased HMG-CoAR activity; and
reduced total cellular cholesterol and its synthesis in both cell lines. Studies
of C4-2B4 orthotopic NCr-nu/nu mice further demonstrated that combination of
simvastatin and metformin (3.5-7.0 MUg/g body weight simvastatin and 175-350
MUg/g body weight metformin) daily by oral gavage over a 9-week period
significantly inhibited primary ventral prostate tumor formation, cachexia, bone
metastasis, and biochemical failure more effectively than 24 MUg/g body weight
docetaxel intraperitoneally injected every 3 weeks, 7.0 MUg/g/day simvastatin, or
350 MUg/g/day metformin treatment alone, with significantly less toxicity and
mortality than docetaxel, establishing combination of simvastatin and metformin
as a promising chemotherapeutic alternative for metastatic CRPC.
PMID- 25122067
TI - The CDK4/6 inhibitor LY2835219 overcomes vemurafenib resistance resulting from
MAPK reactivation and cyclin D1 upregulation.
AB - B-RAF selective inhibitors, including vemurafenib, were recently developed as
effective therapies for melanoma patients with B-RAF V600E mutation. However,
most patients treated with vemurafenib eventually develop resistance largely due
to reactivation of MAPK signaling. Inhibitors of MAPK signaling, including MEK1/2
inhibitor trametinib, failed to show significant clinical benefit in patients
with acquired resistance to vemurafenib. Here, we describe that cell lines with
acquired resistance to vemurafenib show reactivation of MAPK signaling and
upregulation of cyclin D1 and are sensitive to inhibition of LY2835219, a
selective inhibitor of cyclin-dependent kinase (CDK) 4/6. LY2835219 was
demonstrated to inhibit growth of melanoma A375 tumor xenografts and delay tumor
recurrence in combination with vemurafenib. Furthermore, we developed an in vivo
vemurafenib-resistant model by continuous administration of vemurafenib in A375
xenografts. Consistently, we found that MAPK is reactivated and cyclin D1 is
elevated in vemurafenib-resistant tumors, as well as in the resistant cell lines
derived from these tumors. Importantly, LY2835219 exhibited tumor growth
regression in a vemurafenib-resistant model. Mechanistic analysis revealed that
LY2835219 induced apoptotic cell death in a concentration-dependent manner in
vemurafenib-resistant cells whereas it primarily mediated cell-cycle G1 arrest in
the parental cells. Similarly, RNAi-mediated knockdown of cyclin D1 induced
significantly higher rate of apoptosis in the resistant cells than in parental
cells, suggesting that elevated cyclin D1 activity is important for the survival
of vemurafenib-resistant cells. Altogether, we propose that targeting cyclin D1
CDK4/6 signaling by LY2835219 is an effective strategy to overcome MAPK-mediated
resistance to B-RAF inhibitors in B-RAF V600E melanoma.
PMID- 25122065
TI - Genetic alterations affecting cholesterol metabolism and human fertility.
AB - Single nucleotide polymorphisms (SNPs) represent genetic variations among
individuals in a population. In medicine, these small variations in the DNA
sequence may significantly impact an individual's response to certain drugs or
influence the risk of developing certain diseases. In the field of reproductive
medicine, a significant amount of research has been devoted to identifying
polymorphisms which may impact steroidogenesis and fertility. This review
discusses current understanding of the effects of genetic variations in
cholesterol metabolic pathways on human fertility that bridge novel linkages
between cholesterol metabolism and reproductive health. For example, the role of
the low-density lipoprotein receptor (LDLR) in cellular metabolism and human
reproduction has been well studied, whereas there is now an emerging body of
research on the role of the high-density lipoprotein (HDL) receptor scavenger
receptor class B type I (SR-BI) in human lipid metabolism and female
reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene
or other genes related to lipid metabolism impact human physiology is essential
and will play a major role in the development of personalized medicine for
improved diagnosis and treatment of infertility.
PMID- 25122068
TI - Integrated analysis of transcriptomes of cancer cell lines and patient samples
reveals STK11/LKB1-driven regulation of cAMP phosphodiesterase-4D.
AB - The recent proliferation of data on large collections of well-characterized
cancer cell lines linked to therapeutic drug responses has made it possible to
identify lineage- and mutation-specific transcriptional markers that can help
optimize implementation of anticancer agents. Here, we leverage these resources
to systematically investigate the presence of mutation-specific transcription
markers in a wide variety of cancer lineages and genotypes. Sensitivity and
specificity of potential transcriptional biomarkers were simultaneously analyzed
in 19 cell lineages grouped into 228 categories based on the mutational genotypes
of 12 cancer-related genes. Among a total of 1,455 category-specific expression
patterns, the expression of cAMP phosphodiesterase-4D (PDE4D) with 11 isoforms,
one of the PDE4(A-D) subfamilies, was predicted to be regulated by a mutant form
of serine/threonine kinase 11 (STK11)/liver kinase B1 (LKB1) present in lung
cancer. STK11/LKB1 is the primary upstream kinase of adenine monophosphate
activated protein kinase (AMPK). Subsequently, we found that the knockdown of
PDE4D gene expression inhibited proliferation of STK11-mutated lung cancer lines.
Furthermore, challenge with a panel of PDE4-specific inhibitors was shown to
selectively reduce the growth of STK11-mutated lung cancer lines. Thus, we show
that multidimensional analysis of a well-characterized large-scale panel of
cancer cell lines provides unprecedented opportunities for the identification of
unexpected oncogenic mechanisms and mutation-specific drug targets.
PMID- 25122070
TI - Prostate cancer cell response to paclitaxel is affected by abnormally expressed
securin PTTG1.
AB - PTTG1 protein, the human securin, has a central role in sister chromatid
separation during mitosis, and its altered expression has been reported in many
tumor types. Paclitaxel is a widely used chemotherapeutic drug, whose mechanism
of action is related to its ability to arrest cells in mitosis and the subsequent
induction of the intrinsic apoptotic pathway. By using two prostate cancer cell
lines with different responses to paclitaxel treatment, we have identified two
situations in which PTTG1 influences cell fate differentially. In slippage-prone
PC3 cells, both PTTG1 downregulation and overexpression induce an increase in
mitotic cells that is associated with diminished apoptosis after paclitaxel
treatment. In LNCaP cells, however, PTTG1 downregulation prevents mitotic entry
and, subsequently, inhibits mitosis-associated, paclitaxel-induced apoptosis. In
contrast, PTTG1 overexpression induces an increase in mitotic cells and apoptosis
after paclitaxel treatment. We have also identified a role for Mcl-1 protein in
preventing apoptosis during mitosis in PC3 cells, as simultaneous PTTG1 and Mcl-1
silencing enhances mitosis-associated apoptosis after paclitaxel treatment. The
finding that a more efficient mitotic arrest alone in PC3 cells is not enough to
increase apoptosis was also confirmed with the observation that a selected
paclitaxel-resistant PC3 cell line showed an apoptosis-resistant phenotype
associated with increased mitosis upon paclitaxel treatment. These findings could
contribute to identify putative responsive and nonresponsive cells and help us to
approach incomplete responses to paclitaxel in the clinical setting.
PMID- 25122072
TI - In vitro selection, characterization, and biosensing application of high-affinity
cylindrospermopsin-targeting aptamers.
AB - Contamination of freshwater with cyanotoxin cylindrospermopsin (CYN) represents a
significant global concern for public health. The sensitive detection of CYN is
necessary to effectively manage and control the treatment of water resources.
Here we report a novel, highly sensitive label-free aptasensor for CYN analysis,
using aptamers as specific receptors. We have selected the DNA aptamers from a
diverse random library using the in vitro screening SELEX approach. The aptamers
exhibited high affinity for CYN with Kd of nanomolar range. One aptamer exhibited
conformational change upon CYN recognition (CD analysis) and was used to
fabricate the label-free impedimetric aptasensor for CYN. A self-assembled
monolayer from a disulfide-derivatized aptamer was formed on a gold electrode to
fabricate the aptasensor. Upon CYN capturing to the aptasensor surface, a marked
drop in the electron transfer resistance was obtained, which was used as the
principle of detection of CYN. This resulted from the aptamer's conformational
change induced by CYN recognition. The present aptasensor could detect CYN with
the limit of detection as low as 100 pM and a wide linear range of 0.1 to 80 nM.
When mounted on the gold surface, the aptamer exhibited a lower dissociation
constant for CYN than that observed in the fluorescence assay, implying that the
anchoring of the aptamer on the Au surface improved its affinity to CYN.
Moreover, the aptasensor showed high specificity toward other coexistent
cyanobacterial toxins of microcystin-LR and Anatoxin-a. Further biosensor designs
will be generated using those aptamers for simple and sensitive CYN monitoring.
PMID- 25122074
TI - Fully solution-processed transparent conducting oxide-free counter electrodes for
dye-sensitized solar cells: spray-coated single-wall carbon nanotube thin films
loaded with chemically-reduced platinum nanoparticles.
AB - We report fully solution-processed fabrication of transparent conducting oxide
free counter electrodes (CEs) for dye-sensitized solar cells (DSSCs) by combining
spray-coating of single-wall carbon nanotubes (SWCNTs) and chemical reduction of
chloroplatinic acid precursor to platinum nanoparticles (Pt NPs) with formic
acid. The power conversion efficiency of a semitransparent DSSC with such SWCNT
based CE loaded with Pt NPs is comparable to that of a control device with a
conventional CE. Quantification of Pt loading shows that network morphology of
entangled SWCNTs is efficient in forming and retaining chemically reduced Pt NPs.
Moreover, electron microscopy and electrochemical impedance spectroscopy results
show that mainly Pt NPs, which are tens of nanometers in diameter and reside at
the surface of SWCNT CEs, contribute to electrocatalytic activity for triiodide
reduction, to which we attribute strong correlation between power conversion
efficiency of DSSCs and time constant deduced from equivalent-circuit analysis of
impedance spectra.
PMID- 25122069
TI - Drug repurposing identifies a synergistic combination therapy with imatinib
mesylate for gastrointestinal stromal tumor.
AB - Gastrointestinal stromal tumor (GIST) is a rare and therefore often neglected
disease. Introduction of the kinase inhibitor imatinib mesylate radically
improved the clinical response of patients with GIST; however, its effects are
often short-lived, with GISTs demonstrating a median time-to-progression of
approximately two years. Although many investigational drugs, approved first for
other cancers, have been subsequently evaluated for the management of GIST, few
have greatly affected the overall survival of patients with advanced disease. We
employed a novel, focused, drug-repurposing effort for GIST, including imatinib
mesylate-resistant GIST, evaluating a large library of FDA-approved drugs
regardless of current indication. As a result of the drug-repurposing screen, we
identified eight FDA-approved drugs, including fludarabine phosphate (F-AMP),
that showed synergy with and/or overcame resistance to imatinib mesylate. F-AMP
induces DNA damage, Annexin V, and caspase-3/7 activities as the cytotoxic
effects on GIST cells, including imatinib mesylate-resistant GIST cells. F-AMP
and imatinib mesylate combination treatment showed greater inhibition of GIST
cell proliferation when compared with imatinib mesylate and F-AMP alone.
Successful in vivo experiments confirmed the combination of imatinib mesylate
with F-AMP enhanced the antitumor effects compared with imatinib mesylate alone.
Our results identified F-AMP as a promising, repurposed drug therapy for the
treatment of GISTs, with potential to be administered in combination with
imatinib mesylate or for treatment of imatinib mesylate-refractory tumors.
PMID- 25122073
TI - Anal heterosex among young people and implications for health promotion: a
qualitative study in the UK.
AB - OBJECTIVE: To explore expectations, experiences and circumstances of anal sex
among young people. DESIGN: Qualitative, longitudinal study using individual and
group interviews. PARTICIPANTS: 130 men and women aged 16-18 from diverse social
backgrounds. SETTING: 3 contrasting sites in England (London, a northern
industrial city, rural southwest). RESULTS: Anal heterosex often appeared to be
painful, risky and coercive, particularly for women. Interviewees frequently
cited pornography as the 'explanation' for anal sex, yet their accounts revealed
a complex context with availability of pornography being only one element. Other
key elements included competition between men; the claim that 'people must like
it if they do it' (made alongside the seemingly contradictory expectation that it
will be painful for women); and, crucially, normalisation of coercion and
'accidental' penetration. It seemed that men were expected to persuade or coerce
reluctant partners. CONCLUSIONS: Young people's narratives normalised coercive,
painful and unsafe anal heterosex. This study suggests an urgent need for harm
reduction efforts targeting anal sex to help encourage discussion about mutuality
and consent, reduce risky and painful techniques and challenge views that
normalise coercion.
PMID- 25122071
TI - Lipid catabolism via CPT1 as a therapeutic target for prostate cancer.
AB - Prostate cancer is the most commonly diagnosed malignancy among Western men and
accounts for the second leading cause of cancer-related deaths. Prostate cancer
tends to grow slowly and recent studies suggest that it relies on lipid fuel more
than on aerobic glycolysis. However, the biochemical mechanisms governing the
relationships between lipid synthesis, lipid utilization, and cancer growth
remain unknown. To address the role of lipid metabolism in prostate cancer, we
have used etomoxir and orlistat, clinically safe drugs that block lipid oxidation
and lipid synthesis/lipolysis, respectively. Etomoxir is an irreversible
inhibitor of the carnitine palmitoyltransferase (CPT1) enzyme that decreases beta
oxidation in the mitochondria. Combinatorial treatments using etomoxir and
orlistat resulted in synergistic decreased viability in LNCaP, VCaP, and patient
derived benign and prostate cancer cells. These effects were associated with
decreased androgen receptor expression, decreased mTOR signaling, and increased
caspase-3 activation. Knockdown of CPT1A enzyme in LNCaP cells resulted in
decreased palmitate oxidation but increased sensitivity to etomoxir, with
inactivation of AKT kinase and activation of caspase-3. Systemic treatment with
etomoxir in nude mice resulted in decreased xenograft growth over 21 days,
underscoring the therapeutic potential of blocking lipid catabolism to decrease
prostate cancer tumor growth.
PMID- 25122076
TI - Limitation of activity due to chronic conditions United States, 1969 and 1970.
AB - During 1969 and 1970 an estimated average of 23,237,000 persons, about 11.7
percent of the civilian, noninstitutionalized population of the United States,
were reported in health interviews to be limited to some extent as a result of
chronic disease or impairment. Limitation of activity is a measure of long-term
disability resulting from chronic conditions. It is defined as inability to carry
on the major activity for one's age-sex group, such as working, keeping house, or
going to school; restriction in the amount or kind of major activity; or
restriction in relation to other activities, such as recreational, church, or
civic interests.
PMID- 25122075
TI - Noise-assisted charge pump in elastically deformable molecular junctions.
AB - We study a charge pump realized with an elastically deformable quantum dot whose
center of mass follows a nonlinear stochastic dynamics. The interplay of noise,
nonlinear effects, dissipation and interaction with an external time-dependent
driving on the pumped charge is fully analyzed. The results show that the quantum
pumping mechanism not only is not destroyed by the force fluctuations, but it
becomes stronger when the forcing signal frequency is tuned close to the
resonance of the vibrational mode. The robustness of the quantum pump with
temperature is also investigated and an exponential decay of the pumped charge is
found when the coupling to the vibrational mode is present. Implications of our
results for nanoelectromechanical systems are also discussed.
PMID- 25122077
TI - Septic arthritis and acute rheumatic fever in children: the diagnostic value of
serological inflammatory markers.
AB - INTRODUCTION: Joint pain and raised inflammatory markers are features of both
acute rheumatic fever (ARF) and septic arthritis, often posing a diagnostic
challenge to clinicians. Important differences in the presenting serological
inflammatory marker profile may assist patient diagnosis, however, as clinical
experience suggests that ARF is associated with a higher erythrocyte
sedimentation rate (ESR), whereas other serological markers may be similarly
elevated in these 2 conditions. OBJECTIVE: The goal of this study was to
determine the diagnostic value of serological inflammatory markers and white cell
count (WCC) in children presenting with acute joint pain secondary to ARF or
septic arthritis. METHODS: Data were obtained from the Auckland regional
rheumatic fever database and hospital computer records between 2005 and 2012.
Records of all patients under the age of 16 years who were admitted with a new
diagnosis of ARF or septic arthritis were analyzed. The diagnosis of ARF was
defined on the basis of the New Zealand modification of the Jones Criteria, and
the diagnosis of septic arthritis was defined on the basis of joint fluid
cytology and culture. Baseline characteristics, serological inflammatory markers,
and serum WCC were compared between the ARF and septic arthritis patient groups.
RESULTS: Children with ARF displayed significantly higher ESR, higher serum C
reactive protein, and lower serum WCC than children with septic arthritis on
presentation to hospital. In children presenting with monoarthritis, an ESR>64.5,
serum WCC<12.1*109/L, and age above 8.5 years were found to be significant
independent predictors of ARF. Children with all 3 predictors had a 71% risk for
ARF and a 29% risk for septic arthritis. A significant proportion (30%) of
children with the final diagnosis of ARF initially presented with monoarthritis;
14% of these children (5/34) had received nonsteroidal anti-inflammatory
medication before hospital presentation, and 74% of these children (25/34) had
abnormal echocardiograms on admission. CONCLUSIONS: ARF and septic arthritis are
important diagnoses to consider in children presenting with acute joint pain in
New Zealand. A significant proportion of patients with ARF initially present with
acute monoarthritis. Serological inflammatory markers and WCC on presentation
differ significantly between children with ARF and septic arthritis.
PMID- 25122079
TI - Comment on Morin et al "Positive Communication Paradigm Decreases Early
Recurrence in Clubfoot Treatment".
PMID- 25122078
TI - Congenital tibial deficiency: a 37-year experience at 1 institution.
AB - BACKGROUND: The purpose of this study is to evaluate all cases of tibial
deficiency seen at a single institution from 1975 to 2012, to classify these
cases by the Jones classification if possible, to evaluate for associated
anomalies, and to review the surgical treatments provided to these patients.
METHODS: Ninety-five patients (125 extremities) treated at our institution
between 1975 and 2012 with tibial deficiency had complete records allowing for
classification and review of full treatment course. These patients' records and
imaging were retrospectively reviewed for any associated anomalies, surgical
treatment performed, and limb deformity characterized by the Jones classification
where possible. RESULTS: Seventy-three of 125 limbs (58%) were classified as
Jones type 1A, 6 (5%) as type 1B, 18 (14%) as type 2, and 12 (10%) as type 4. Two
limbs initially classified radiographically as type 3 deformities subsequently
developed a proximal tibia epiphyses and thus did not represent true type 3
deformities. Fourteen limbs (11%) were characterized by global tibial deficiency
but with proximal and distal epiphyses and could not be classified according to
the Jones classification. Seventy-five of the 95 patients (79%) had associated
anomalies. Other lower extremity anomalies were most frequent; however, upper
extremity, spine, and visceral anomalies were also noted. CONCLUSIONS: True type
3 deformity as described by Jones was not seen in our patient population; all
patients developed a proximal epiphysis. Therefore, this group may be better
served by limb salvage than amputation. Fourteen (11%) limbs, characterized by
global tibia shortening relative to the fibula of variable degree, could not be
classified according to the Jones classification. We propose adding this group as
a new group within the Jones classification, which we call type 5. Finally, in
this patient population, the Brown procedure for type 1 tibial deficiency
universally failed, confirming results of prior studies. LEVEL OF EVIDENCE: This
is a level IV study, a retrospective review of 95 patients with tibial deficiency
from a single institution.
PMID- 25122080
TI - Calf circumference discrepancies in patients with unilateral clubfoot: Ponseti
versus surgical release.
AB - BACKGROUND: Talipes equinovarus is the most common congenital lower limb
abnormality. Decreased calf size has been found to have negative impacts on
patients' subjective appraisals of long-term outcomes. This study compares calf
circumference ratios in 2 groups of patients with unilateral clubfoot, those
treated according to the Ponseti method and those treated with extensive surgery,
to determine whether the current standard of care achieves better anatomic
outcomes. METHODS: Patients >1 year after treatment for unilateral clubfoot were
recruited during normal follow-up appointments and both calves were measured
using a standardized protocol. A questionnaire concerning their treatment history
was also completed. Data were analyzed by comparing calf circumference ratios
between treatment modalities. RESULTS: Thirty-five patients with unilateral
clubfoot were recruited after satisfying inclusion criteria. Twenty-four (69%)
were included in the Ponseti-managed group, and 11 (31%) were in the extensive
surgery group. The affected legs were on average 3% to 10% smaller than the
control legs across all groups. The surgery group's average calf ratio was
significantly less at 90.8%+/-3.5% compared with 94.4%+/-3.3% in the Ponseti
group. CONCLUSIONS: The calf circumference of limbs affected by clubfoot is
significantly smaller in those treated with extensive surgery as compared with
those treated with the Ponseti method alone, with or without percutaneous
tenotomy. This supports the Ponseti method as the standard of care for achieving
the most favorable anatomic outcome. LEVEL OF EVIDENCE: Level I.
PMID- 25122081
TI - What's new in Shock? September 2014.
PMID- 25122083
TI - Impact of arterial oxygen tension on venous oxygen saturation.
PMID- 25122082
TI - Remote ischemic preconditioning mitigates myocardial and neurological dysfunction
via K(ATP) channel activation in a rat model of hemorrhagic shock.
AB - Severe hemorrhagic shock and resuscitation is a state of global body ischemia and
reperfusion that causes myocardial and cerebral dysfunction. We investigated
whether remote ischemic preconditioning (RIPC) would reduce myocardial and
cerebral ischemia and reperfusion injuries after hemorrhagic shock as the result
of the K(ATP) channel activation. Twenty-one male rats were randomized into three
groups: RIPC, RIPC with K(ATP) channel blocker, and control. Remote ischemic
preconditioning was induced by four cycles of 5 min of limb ischemia followed by
reperfusion for 5 min. Hemorrhagic shock was induced by removing 50% of the
estimated total blood volume during an interval of 1 h. Thirty minutes after the
completion of bleeding, the animals were reinfused with shed blood during the
ensuing 30 min. The animals were monitored for 2 h and observed for an additional
72 h. Myocardial function was measured by echocardiography, and sublingual
microcirculation was measured by a sidestream dark-field imaging device at
baseline, 1 h after bleeding, 30 min after the completion of bleeding, 30 min
after reinfusion, and hourly intervals thereafter. The survival and neurological
function were evaluated at 12, 24, 48, and 72 h after reinfusion. At 2 h after
reinfusion, ejection fraction and myocardial performance index were significantly
better in the RIPC group than in the control group (P < 0.01). The sublingual
microvascular flow index and perfused vessel density were significantly greater
after reinfusion in the RIPC group than that in the control group (P < 0.01). The
duration of survival was significantly longer, and neurological deficit score was
significantly better in the RIPC group than the control animals (P < 0.01).
Pretreatment with the K(ATP) channel blocker (glibenclamide) completely abolished
the myocardial and cerebral protective effects of RIPC. We demonstrate, for the
first time, that after severe hemorrhagic shock and resuscitation, RIPC mitigated
myocardial and neurological dysfunction with improved survival by activation of
the K(ATP) channel.
PMID- 25122084
TI - Reply: To PMID 24667613.
PMID- 25122085
TI - X-ray scattering from immunostimulatory tetrapod-shaped DNA in aqueous solution
to explore its biological activity-conformation relationship.
AB - We carried out synchrotron X-ray scattering experiments from four DNA
supermolecules designed to form tetrapod shapes; these supermolecules had
different sequences but identical numbers of total base pairs, and each contained
an immunostimulatory CpG motif. We confirmed that the supermolecules did indeed
form the expected tetrapod shape. The sample that had the largest radius of
gyration (Rg) induced the most cytokine secretion from cultured immune cells.
Structural analysis in combination with a rigid tetrapod model and an atomic
scale DNA model revealed that the larger Rg can be ascribed to dissociation of
the DNA double strands in the central connecting portion of the DNA tetrapod.
This finding suggests that the biological activity is related to the ease with
which single DNA strands can be formed.
PMID- 25122087
TI - Antioxidants and respiratory disease: the uric acid paradox.
PMID- 25122086
TI - Epigenetic landscapes explain partially reprogrammed cells and identify key
reprogramming genes.
AB - A common metaphor for describing development is a rugged "epigenetic landscape"
where cell fates are represented as attracting valleys resulting from a complex
regulatory network. Here, we introduce a framework for explicitly constructing
epigenetic landscapes that combines genomic data with techniques from spin-glass
physics. Each cell fate is a dynamic attractor, yet cells can change fate in
response to external signals. Our model suggests that partially reprogrammed
cells are a natural consequence of high-dimensional landscapes, and predicts that
partially reprogrammed cells should be hybrids that co-express genes from
multiple cell fates. We verify this prediction by reanalyzing existing datasets.
Our model reproduces known reprogramming protocols and identifies candidate
transcription factors for reprogramming to novel cell fates, suggesting
epigenetic landscapes are a powerful paradigm for understanding cellular
identity.
PMID- 25122088
TI - Response to: Domiciliary long term non-invasive ventilation in COPD: should we
select subgroups with a better likelihood to respond to NIV in subsequent
randomised controlled trials?
PMID- 25122089
TI - Spinosad and the tomato borer Tuta absoluta: a bioinsecticide, an invasive pest
threat, and high insecticide resistance.
AB - The introduction of an agricultural pest species into a new environment is a
potential threat to agroecosystems of the invaded area. The phytosanitary concern
is even greater if the introduced pest's phenotype expresses traits that will
impair the management of that species. The invasive tomato borer, Tuta absoluta
(Meyrick) (Lepidoptera: Gelechiidae), is one such species and the
characterization of the insecticide resistance prevailing in the area of origin
is important to guide management efforts in new areas of introduction. The
spinosad is one the main insecticides currently used in Brazil for control of the
tomato borer; Brazil is the likely source of the introduction of the tomato borer
into Europe. For this reason, spinosad resistance in Brazilian populations of
this species was characterized. Spinosad resistance has been reported in
Brazilian field populations of this pest species, and one resistant population
that was used in this study was subjected to an additional seven generations of
selection for spinosad resistance reaching levels over 180,000-fold. Inheritance
studies indicated that spinosad resistance is monogenic, incompletely recessive
and autosomal with high heritability (h(2) = 0.71). Spinosad resistance was
unstable without selection pressure with a negative rate of change in the
resistance level ( = -0.51) indicating an associated adaptive cost. Esterases and
cytochrome P450-dependent monooxygenases titration decreased with spinosad
selection, indicating that these detoxification enzymes are not the underlying
resistance mechanism. Furthermore, the cross-resistance spectrum was restricted
to the insecticide spinetoram, another spinosyn, suggesting that altered target
site may be the mechanism involved. Therefore, the suspension of spinosyn use
against the tomato borer would be a useful component in spinosad resistance
management for this species. Spinosad use against this species in introduced
areas should be carefully monitored to prevent rapid selection of high levels of
resistance and the potential for its spread to new areas.
PMID- 25122091
TI - A life-course approach to human reproduction.
PMID- 25122092
TI - Griefwork online: perinatal loss, lifecourse disruption and online support.
AB - The Internet provides new opportunities for accessing and giving support
following perinatal loss and in this article we report on a project concerned to
explore the use of social networking and online networks following such an
experience. Perinatal loss can be defined and perceived as biographical
disruption yet this type of loss sometimes lacks social recognition. Our
ethnographic study reveals that not only do mothers, and sometimes fathers and
grandmothers, seek support on the Internet but they also engage in griefwork (the
work the bereaved do with others).
PMID- 25122090
TI - EVA-1 functions as an UNC-40 Co-receptor to enhance attraction to the MADD-4
guidance cue in Caenorhabditis elegans.
AB - We recently discovered a secreted and diffusible midline cue called MADD-4 (an
ADAMTSL) that guides migrations along the dorsoventral axis of the nematode
Caenorhabditis elegans. We showed that the transmembrane receptor, UNC-40 (DCC),
whose canonical ligand is the UNC-6 (netrin) guidance cue, is required for
extension towards MADD-4. Here, we demonstrate that MADD-4 interacts with an EVA
1/UNC-40 co-receptor complex to attract cell extensions. EVA-1 is a conserved
transmembrane protein with predicted galactose-binding lectin domains. EVA-1
functions in the same pathway as MADD-4, physically interacts with both MADD-4
and UNC-40, and enhances UNC-40's sensitivity to the MADD-4 cue. This enhancement
is especially important in the presence of UNC-6. In EVA-1's absence, UNC-6
interferes with UNC-40's responsiveness to MADD-4; in UNC-6's absence, UNC-40's
responsiveness to MADD-4 is less dependent on EVA-1. By enabling UNC-40 to
respond to MADD-4 in the presence of UNC-6, EVA-1 may increase the precision by
which UNC-40-directed processes can reach their MADD-4-expressing targets within
a field of the UNC-6 guidance cue.
PMID- 25122093
TI - Sex differences in predicting chronicity of low-back pain after acute trauma
using lumbar muscle area.
AB - OBJECTIVE: The aim of this study was to investigate sex differences in predicting
chronicity of low-back pain after acute trauma using cross-sectional areas of
paraspinal (multifidus and erector spinae) and psoas muscles. DESIGN: Between
January 2006 and December 2010, a total of 54 patients were interviewed at least
6 mos after the trauma event. The subjects were classified into chronic low-back
pain group and improved low-back pain group according to the presence of low-back
pain for more than 6 mos. The cross-sectional area of the multifidus, erector
spinae, and psoas muscles was measured at the level of the lower margin of the L3
and L5 vertebrae using magnetic resonance imaging. RESULTS: The cross-sectional
area of the multifidus and erector spinae muscles at L5 in the chronic low-back
pain group was significantly smaller than that of the improved low-back pain
group (P < 0.05) in the men. There were no significant differences in the other
parameters between the groups in the men. There were no significant differences
in any parameters in the women. CONCLUSIONS: In the men, the cross-sectional area
of the multifidus and erector spinae muscles at the lower lumbar level can be
considered to be prognostic factors for the chronic low-back pain after acute
trauma. The authors thus suggest that strengthening of lumbar paraspinal muscles
could be helpful for preventing chronicity of low-back pain.
PMID- 25122094
TI - Men with early degrees of knee osteoarthritis present functional and
morphological impairments of the quadriceps femoris muscle.
AB - OBJECTIVE: Quadriceps muscle weakness is common in knee osteoarthritis (OA).
Reasons for weakness may include atrophy, reduction in the muscle fibers number,
and changes in the muscle activation. It is uncertain when these muscular changes
begin to appear. Therefore, the purpose of this study was to determine whether
men with early stages of knee OA already had functional and quadriceps muscle
morphologic alterations. DESIGN: Forty men were divided into two groups: control
group (healthy subjects) and OA group (subjects with knee OA). A biopsy of the
vastus lateralis muscle was performed for morphometric analysis. Isokinetic
evaluation of knee extensor torque, concentric and eccentric (90 and 180
degrees/sec), was performed simultaneously with vastus lateralis
electromyographic activity evaluation. RESULTS: Significant differences were
found in knee extensor torque (P < 0.05) and in normalized root mean square (P <
0.01) during the eccentric contractions (both velocities), with higher values for
the control group. No differences were found during concentric contractions. The
OA group presented greater values of the minimum diameter of type 1 fibers and
greater proportion and relative cross-sectional area of type 2b fibers (P <
0.05). CONCLUSIONS: Men with early stages of knee OA do not present alterations
of concentric strength but had decreased eccentric strength and morphologic
quadriceps muscle changes, indicating neuromuscular adaptations.
PMID- 25122095
TI - Review of secondary health conditions in postpolio syndrome: prevalence and
effects of aging.
AB - OBJECTIVE: This study sought to better understand the prevalence and the severity
of secondary health conditions in individuals with postpolio syndrome (PPS) as
well as the association between these conditions and aging. DESIGN: A scoping
literature review was conducted searching electronic databases for studies
published from 1986 to 2011. The scoping review provided information regarding
the prevalence and associations of secondary health conditions in PPS with age or
other duration-related variables. RESULTS: The findings indicate that (1)
individuals with PPS experience a number of serious secondary health conditions;
(2) the most common conditions or symptoms are fatigue, pain, respiratory and
sleep complaints, and increased risk for falls; (3) reports of the associations
between the frequency or the severity of conditions and age-related factors are
variable, perhaps because of methodological inconsistencies between studies; and
(4) there is a marked lack of longitudinal research examining the natural course
of health conditions in people aging with PPS. CONCLUSIONS: Longitudinal research
is needed to understand the course of health conditions and the impact of
multiple secondary conditions in people aging with PPS. Efforts are also needed
to develop and test the efficacy of interventions to prevent these secondary
health conditions or reduce their negative impact.
PMID- 25122096
TI - Effect of hip abduction exercise with manual pelvic fixation on recruitment of
deep trunk muscles.
AB - OBJECTIVE: The aim of this study was to determine whether side-lying hip
abduction exercise while applying manual pelvic fixation is more effective than
hip abduction without manual pelvic fixation for promoting deep trunk muscle
activity. DESIGN: This is a cross-sectional study comparing deep trunk muscle
activation between hip abduction exercise without and with manual pelvic fixation
in ten participants. Muscle activation was measured using fine-wire and surface
electromyography. RESULTS: Hip abduction with manual pelvic fixation was found to
result in significantly more recruitment of all studied deep trunk muscles except
the ipsilateral obliquus externus compared with hip abduction without manual
pelvic fixation (P < 0.05). The greatest increased activation was seen in the
ipsilateral deep and superficial multifidus. The increase in deep multifidus
percentage of maximal voluntary contraction was greater than that of the rectus
abdominis, the obliquus externus, the transversuus abdominis/obliquus internus,
the lumbar erector spinae, the superficial multifidus, and the gluteus medius (P
< 0.05). The superficial multifidus percentage of maximal voluntary contraction
was significantly increased over that of the rectus abdominis and the obliquus
externus (P < 0.05). Moderate correlation between deep and superficial multifidus
activation was found (Pearson correlation coefficient, 0.537). CONCLUSIONS: Hip
abduction training in the side-lying position while applying manual pelvic
fixation seems to be more effective for recruiting deep trunk muscles for dynamic
lumbar spinal stabilization.
PMID- 25122097
TI - Strength training associated with task-oriented training to enhance upper-limb
motor function in elderly patients with mild impairment after stroke: a
randomized controlled trial.
AB - OBJECTIVE: The aim of this study was to verify the effects of loaded exercises
associated with a task-oriented training (TOT) program in the recovery of upper
limb function in individuals with chronic hemiparesis after stroke. DESIGN: This
study used a single-blinded, randomized controlled trial. Patients were included
into two TOT groups: one that performed the task-oriented therapy without load
(TOT group, n = 10) and another one that performed task-oriented therapy with
personalized resistance (TOT_ST group, n = 10) for 6 wks, for a total of 12
sessions. Main measures included The Upper Extremity Performance Test, shoulder
flexor and handgrip strength, shoulder active range of motion, motor impairment
(Fugl-Meyer Scale), and muscle tone. RESULTS: The TOT_ST group demonstrated
better scores relating to unilateral tasks and in the quality aspects of
bilateral movements (The Upper Extremity Performance Test, P = 0.04) at the end
of rehabilitation protocol. The highest muscle force gain was reached by the
TOT_ST group for the shoulder flexors (P = 0.001). Similarly, the active range of
motion (P = 0.01) and Fugl-Meyer scores (P = 0.001) were higher in the TOT_ST
group compared with the TOT group. Both groups showed improvement after training.
CONCLUSIONS: Strength training was able to intensify the upper-limb
rehabilitation, as demonstrated by the superior scores achieved by the TOT_ST
group in most of the evaluated parameters. Muscle strength training might be a
pivotal element of the task-oriented rehabilitation program of chronic patients
with mild impairment after stroke.
PMID- 25122098
TI - Simultaneous bilateral biceps tendon rupture: a case report with practical
sonographic diagnosis.
AB - Simultaneous bilateral complete tear of the biceps tendons is a rare clinical
entity with challenging treatment approaches. Current diagnostic imaging of
rupture of the biceps tendon has reverted to magnetic resonance imaging; however,
in the recent years, sonography has been widely used in musculoskeletal practice.
The authors present a case of simultaneous bilateral biceps tendon rupture
diagnosed on the basis of fundamental sonographic findings of the torn biceps
tendons.
PMID- 25122099
TI - Effects of low-level laser therapy on skeletal muscle repair: a systematic
review.
AB - A review of the literature was performed to demonstrate the most current
applicability of low-level laser therapy (LLLT) for the treatment of skeletal
muscle injuries, addressing different lasers, irradiation parameters, and
treatment results in animal models. Searches were performed in the
PubMed/MEDLINE, SCOPUS, and SPIE Digital Library databases for studies published
from January 2006 to August 2013 on the use of LLLT for the repair of skeletal
muscle in any animal model. All selected articles were critically appraised by
two independent raters. Seventeen of the 36 original articles on LLLT and muscle
injuries met the inclusion criteria and were critically evaluated. The main
effects of LLLT were a reduction in the inflammatory process, the modulation of
growth factors and myogenic regulatory factors, and increased angiogenesis. The
studies analyzed demonstrate the positive effects of LLLT on the muscle repair
process, which are dependent on irradiation and treatment parameters. The
findings suggest that LLLT is an excellent therapeutic resource for the treatment
of skeletal muscle injuries in the short-term.
PMID- 25122100
TI - Lower gastrointestinal bleeding associated with diclofenac topical patch in a
patient with colonic mass and on antiplatelet therapy for atrial fibrillation.
AB - Topical formulations of diclofenac, a nonsteroidal anti-inflammatory drug
commonly prescribed to treat musculoskeletal complaints such as osteoarthritis,
low back pain, and myofascial pain, are available in the form of a solution, gel,
and patch. The topical application of diclofenac results in substantially lower
systemic exposure to diclofenac compared with oral diclofenac, resulting in a
more favorable side effect profile. To the authors' knowledge, this is the first
case report of a lower gastrointestinal bleed associated with diclofenac topical
patch use in a 77 yr-old-woman with a history of colonic mass and atrial
fibrillation on antiplatelet therapy.
PMID- 25122101
TI - Rare communication between the musculocutaneous and median nerves in the forearm:
its clinical significance.
AB - Morphologic classifications of communication between musculocutaneous and median
nerves are not based on the distribution and the function of the communicating
branch. The authors report a rare case of such a communication with passage of
the median nerve through the pronator teres muscle and discuss its clinical
significance. The musculocutaneous nerve was divided into a lateral branch that
continued to the lateral antebrachial cutaneous nerve and a medial branch that
joined the median nerve in the forearm. The authors separated the nerve bundles
and noted that the communicating branch derived from the sixth to seventh
cervical nerves and supplied nerve fibers to the pronator teres muscle and the
proper palmar digital nerve of the thumb. In addition, the median nerve
penetrated the humeral head of the pronator teres muscle. Isolated
musculocutaneous neuropathy with such a communication may cause unexpected
symptoms such as sensory deficit in the palm and muscular weakness of the forearm
and the thumb.
PMID- 25122102
TI - Disease-in-a-dish: the contribution of patient-specific induced pluripotent stem
cell technology to regenerative rehabilitation.
AB - Advances in regenerative medicine technologies will lead to dramatic changes in
how patients in rehabilitation medicine clinics are treated in the upcoming
decades. The multidisciplinary field of regenerative medicine is developing new
tools for disease modeling and drug discovery based on induced pluripotent stem
cells. This approach capitalizes on the idea of personalized medicine by using
the patient's own cells to discover new drugs, increasing the likelihood of a
favorable outcome. The search for compounds that can correct disease defects in
the culture dish is a conceptual departure from how drug screens were done in the
past. This system proposes a closed loop from sample collection from the diseased
patient, to in vitro disease model, to drug discovery and Food and Drug
Administration approval, to delivering that drug back to the same patient. Here,
recent progress in patient-specific induced pluripotent stem cell derivation,
directed differentiation toward diseased cell types, and how those cells can be
used for high-throughput drug screens are reviewed. Given that restoration of
normal function is a driving force in rehabilitation medicine, the authors
believe that this drug discovery platform focusing on phenotypic rescue will
become a key contributor to therapeutic compounds in regenerative rehabilitation.
PMID- 25122103
TI - Core stability, knee muscle strength, and anterior translation are correlated
with postural stability in anterior cruciate ligament-reconstructed patients.
AB - OBJECTIVE: The purpose of this study was to investigate the relationship of
postural stability and lower extremity performance with core stability, knee
laxity, and muscle strength in patients with anterior cruciate ligament
reconstruction. DESIGN: Twenty-eight anterior cruciate ligament-reconstructed
subjects were included in the study. Anterior knee laxity tests, isokinetic knee
muscle strength tests, and core stability tests were performed. Single-limb
postural stability was assessed in both eyes-open and eyes-closed positions on a
static surface and an eyes-open condition on a foam surface. A single-legged hop
test was performed to assess lower extremity performance. To detect differences
between the operated and healthy leg, a Mann-Whitney U test was performed, and a
correlation analysis was performed using the Spearman correlation coefficient.
RESULTS: Knee muscle strength and laxity were different between the operated and
healthy legs (P < 0.05). Postural stability scores correlated with core stability
tests (P < 0.05) in both the operated and healthy legs. In the operated leg, knee
laxity and muscle strength correlated with the mediolateral sway index on a foam
surface (P < 0.05). Knee flexor and extensor muscle strength correlated with the
single-legged hop for both legs (P < 0.05). CONCLUSIONS: Decreased core
stability, decreased knee muscle strength, and increased knee laxity correlated
with single-limb postural stability. Better hop performance was demonstrated with
better knee flexor and extensor muscle strength and was independent from core
stability.
PMID- 25122104
TI - Iliac artery endofibrosis in a middle-aged female long-distance runner.
AB - Exercise-induced iliac artery endofibrosis is a recently described abnormality of
the external iliac artery that typically affects younger, healthy endurance
athletes. Characteristic of the initially termed cyclist's iliac syndrome is
lower limb pain during exercise with rapid recovery after exercise. This
clinically complicated case describes an older female long-distance runner in
whom an incorrect diagnosis of fibromuscular dysplasia was originally made when
she presented with claudication and thrombosis of the right external iliac
artery. A thrombectomy and bilateral balloon angioplasty were performed; however,
her symptoms persisted. Four months later, she unexpectedly complained of dual
calf claudication, a diagnosis of exercise-induced iliac artery endofibrosis was
made, and a bilateral prosthetic graft bypass procedure was performed, which
resulted in a good outcome.
PMID- 25122105
TI - Letter to the editor regarding "Peripheral nerve stimulation compared with usual
care for pain relief of hemiplegic shoulder pain" Am J Phys Med Rehabil 2014;93:
17-27.
PMID- 25122106
TI - Stem cell therapy for intervertebral disk regeneration.
AB - Intervertebral disk degeneration has been considered an irreversible process
characterized by a decrease in cell viability, attenuation of proteoglycan and
type II collagen synthesis, and dehydration of nucleus pulposus. Stem cell
therapy specifically addresses the degenerative process and offers a potentially
effective treatment modality. Current preclinical studies show that mesenchymal
stem cells have the capacity to repair degenerative disks by differentiation
toward chondrocyte-like cells, which produce proteoglycans and type II collagen.
There has been evidence that mesenchymal stem cell transplantation into the
intervertebral disk increases the intradiskal magnetic resonance imaging T2
signal intensity, increases the disk height, and decreases the degenerative grade
in animal models. Appropriate selection of cell carriers/matrix is important
because it may prevent cell leakage into the spinal canal and provide an
environment that facilitates cell proliferation and differentiation. Although
human cell therapy trials for degenerative disk disease are on the horizon,
potential issues might arise. The authors hereby review the current state of
regenerative cell therapy in degenerative disk disease, with emphasis in cell
source, techniques for cellular expansion, induction, transplantation, potential
benefit, and risks of the use of this novel medical armamentarium in the
treatment of degenerative disk disease.
PMID- 25122108
TI - Introduction to the series: Association of Academic Physiatrists research
committee funding priority recommendations.
PMID- 25122107
TI - An etiological paradigm shift for chronic hemiplegic shoulder pain.
PMID- 25122109
TI - Elder abuse in Portugal: findings from the first national prevalence study.
AB - In this study, we present findings of the Portuguese national prevalence study,
"Aging and Violence," the purpose of which was to estimate the prevalence of
abuse and neglect of older people in family settings over a 12-month period and
examine the relationship between abuse and sociodemographic and health
characteristics. Through a telephone survey of a representative probability
sample (N = 1,123), we evaluated 12 abusive behaviors and demographic data.
Overall, 12.3% of older adults experienced elder abuse in family settings. The
prevalence rates of specific types were as follows: psychological, 6.3%;
financial, 6.3%; physical, 2.3%; neglect, 0.4%; and sexual, 0.2%. Logistic
regression was employed to determine the relationship between abuse and
covariates. The study suggests that education level, age, and functional status
are significantly associated with abuse. Accurate estimates of the prevalence of
elder abuse and understanding of victim and perpetrator characteristics are
fundamental to designing effective strategies for prevention and intervention.
PMID- 25122110
TI - Mercury poisoning as a cause of intracranial hypertension.
AB - Mercury poisoning is a rare but fatal toxicologic emergency. Neurologic
manifestations involving the central nervous system are seen usually with chronic
mercury intoxication. The most commonly seen complaints are headache, tremor,
impaired cognitive skills, weakness, muscle atrophy, and paresthesia. Here, we
present a male patient who was chronically exposed to elemental mercury and had
papilledema and intracranial hypertension without parenchymal lesion in the
central nervous system. A 12-year-old male patient was referred to our emergency
room because of severe fatigue, generalized muscle pain and weakness, which was
present for a month. Physical examination revealed painful extremities, decreased
motor strength and the lack of deep tendon reflexes in lower extremities. He had
mixed type polyneuropathy in his electromyography. Whole blood and 24-hour
urinary mercury concentrations were high. A chelation therapy with succimer
(dimercaptosuccinic acid) was started on the fourth day of his admission. On the
seventh day of his admission, he developed headache and nausea, and bilateral
papilledema and intracranial hypertension were detected on physical examination.
Acetazolamide was started and after 1 month of treatment, the fundi examination
was normal. The patient stayed in the hospital for 35 days and was then
discharged with acetazolamide, vitamin B6, gabapentin, and followed as an
outpatient. His clinical findings were relieving day by day. Although headache is
the most common symptom in mercury poisoning, the clinician should evaluate the
fundus in terms of intracranial hypertension.
PMID- 25122111
TI - Rates and characteristics of radiographically detected intracerebral cavernous
malformations after cranial radiation therapy in pediatric cancer patients.
AB - Rates and characteristics of intracerebral cavernous malformations after cranial
radiation therapy remain poorly understood. Herein we report on intracerebral
cavernous malformations detected on follow-up imaging in pediatric cancer
patients who received cranial radiation therapy at age <=18 years from 1980 to
2009. Through chart reviews (n = 362) and phone interviews (n = 104) of a
retrospective cohort, we identified 10 patients with intracerebral cavernous
malformations. The median latency time for detection of intracerebral cavernous
malformations after cranial radiation therapy was 12 years (range 1-24 years) at
a median age of 21.4 years (interquartile range = 15-28). The cumulative
incidence was 3% (95% confidence interval 1%-8%) at 10 years post cranial
radiation therapy and 14% (95% confidence interval 7%-26%) at 15 years. Three
patients underwent surgical resection. Two surgical specimens were pathologically
similar to sporadically occurring intracerebral cavernous malformations; one was
consistent with capillary telangiectasia. Intracerebral cavernous malformations
are common after cranial radiation therapy and can show a spectrum of histologic
features.
PMID- 25122112
TI - Succinic Semialdehyde Dehydrogenase Deficiency in a Chinese Boy: A Novel ALDH5A1
Mutation With Severe Phenotype.
AB - Succinic semialdehyde dehydrogenase deficiency is a rare autosomal recessive
disorder affecting catabolism of the neurotransmitter gamma-aminobutyric acid
(GABA), with a wide range of clinical phenotype. We report a Malaysian Chinese
boy with a severe early onset phenotype due to a previously unreported mutation.
Urine organic acid chromatogram revealed elevated 4-hydroxybutyric acid. Magnetic
resonance imaging (MRI) of the brain demonstrated cerebral atrophy with atypical
putaminal involvement. Molecular genetic analysis showed a novel homozygous 3-bp
deletion at the ALDH5A1 gene c.1501_1503del (p.Glu501del). Both parents were
confirmed to be heterozygotes for the p.Glu501del mutation. The clinical course
was complicated by the development of subdural hemorrhage probably as a result of
rocking the child to sleep for erratic sleep-wake cycles. This case illustrates
the need to recognize that trivial or unintentional shaking of such children,
especially in the presence of cerebral atrophy, can lead to subdural hemorrhage.
PMID- 25122114
TI - Structure of CfaA suggests a new family of chaperones essential for assembly of
class 5 fimbriae.
AB - Adhesive pili on the surface of pathogenic bacteria comprise polymerized pilin
subunits and are essential for initiation of infections. Pili assembled by the
chaperone-usher pathway (CUP) require periplasmic chaperones that assist subunit
folding, maintain their stability, and escort them to the site of bioassembly.
Until now, CUP chaperones have been classified into two families, FGS and FGL,
based on the short and long length of the subunit-interacting loops between its
F1 and G1 beta-strands, respectively. CfaA is the chaperone for assembly of
colonization factor antigen I (CFA/I) pili of enterotoxigenic E. coli (ETEC), a
cause of diarrhea in travelers and young children. Here, the crystal structure of
CfaA along with sequence analyses reveals some unique structural and functional
features, leading us to propose a separate family for CfaA and closely related
chaperones. Phenotypic changes resulting from mutations in regions unique to this
chaperone family provide insight into their function, consistent with involvement
of these regions in interactions with cognate subunits and usher proteins during
pilus assembly.
PMID- 25122115
TI - Transcriptome of American oysters, Crassostrea virginica, in response to
bacterial challenge: insights into potential mechanisms of disease resistance.
AB - The American oyster Crassostrea virginica, an ecologically and economically
important estuarine organism, can suffer high mortalities in areas in the
Northeast United States due to Roseovarius Oyster Disease (ROD), caused by the
gram-negative bacterial pathogen Roseovarius crassostreae. The goals of this
research were to provide insights into: 1) the responses of American oysters to
R. crassostreae, and 2) potential mechanisms of resistance or susceptibility to
ROD. The responses of oysters to bacterial challenge were characterized by
exposing oysters from ROD-resistant and susceptible families to R. crassostreae,
followed by high-throughput sequencing of cDNA samples from various timepoints
after disease challenge. Sequence data was assembled into a reference
transcriptome and analyzed through differential gene expression and functional
enrichment to uncover genes and processes potentially involved in responses to
ROD in the American oyster. While susceptible oysters experienced constant levels
of mortality when challenged with R. crassostreae, resistant oysters showed
levels of mortality similar to non-challenged oysters. Oysters exposed to R.
crassostreae showed differential expression of transcripts involved in immune
recognition, signaling, protease inhibition, detoxification, and apoptosis.
Transcripts involved in metabolism were enriched in susceptible oysters,
suggesting that bacterial infection places a large metabolic demand on these
oysters. Transcripts differentially expressed in resistant oysters in response to
infection included the immune modulators IL-17 and arginase, as well as several
genes involved in extracellular matrix remodeling. The identification of
potential genes and processes responsible for defense against R. crassostreae in
the American oyster provides insights into potential mechanisms of disease
resistance.
PMID- 25122118
TI - Clinical outcome and blood transfusion after infant cardiac surgery with a
routine use of conventional ultrafiltration.
AB - OBJECTIVE: Priming-related hemodilution is the culprit behind excessive body
water accumulation, postoperative coagulopathy and enhanced blood transfusion in
infant cardiac surgery patients. In this retrospective, observational study,
clinical data were analyzed to assess the effect of conventional ultrafiltration
on allogenic blood transfusion and patient clinical outcome. METHODS: All infants
with a bodyweight up to 10 kg who underwent consequent cardiac surgery in 2011
and 2012 were eligible for the audit. Seventy patients, operated in accordance
with existing pediatric protocol, enrolled in the control group. The study group
consisted of 55 patients who were operated employing conventional ultrafiltration
during bypass and recently adjusted hematocrit targets. The following variables
were primarily investigated: hematocrit and colloid osmotic pressure value, total
volume of blood products transfused and duration of postoperative mechanical
ventilation. Secondary outcome measures were: postoperative urine production,
postoperative blood loss, length of stay at the intensive care unit and hospital
stay. RESULTS: There were no significant differences between the groups in
relation to demographics or hematological and cardiopulmonary bypass data. The
ultrafiltration volume removed from circulation during bypass in the study group
was 171 +/- 99 ml. No significant difference between the groups was found with
regard to the total allogenic blood transfusion (study group 216 +/- 92 ml versus
control group 191 +/-93 ml; p = 0.136). All recorded clinical end points,
duration of mechanical ventilation, duration of chest tube in situ, stay in ICU
and stay in hospital, were similar between the groups. CONCLUSIONS: Routine use
of conventional ultrafiltration during the cardiac surgery for patients with a
bodyweight less than 10 kg was a safe technique that allowed us to achieve higher
hematocrit levels at the end of the operation without additional transfusions of
allogenic blood. On the other hand, ultrafiltration did not improve the clinical
end points.
PMID- 25122116
TI - Distinct patterns of the lipid alterations between genotype 1 and 2 chronic
hepatitis C patients after viral clearance.
AB - BACKGROUND: The hepatitis C virus (HCV) genotype-specific impacts on the host
metabolic alterations remained inconclusive. METHODS: A prospective study
including 229 (118 genotype 1 (G1) and 111 G2) consecutive chronic HCV patients
who had completed a course of anti-HCV treatment and underwent pre- and 24 weeks
post-treatment surveys of metabolic profiles was conducted. Patients were
stratified according to the therapeutic response, viral genotype and baseline
insulin resistance (IR: homeostasis model assessments of IR (HOMA-IR) >= 2.5).
Paired t-tests were used to compare the pre- and post-treatment variables.
RESULTS: Significant post-therapeutic increases in cholesterol, triglyceride,
HDL, LDL, apolipoprotein A1 and apolipoprotein B were observed in patients with
sustained virological response (SVR) but not in those without. Among those with
SVR, post-therapeutic increases in HDL (p<0.001) and apolipoprotein A1 (p =
0.012) were only found in G2, whereas increased triglyceride/HDL (p = 0.01)
ratios were only found in G1 patients. When stratified by baseline IR among those
with SVR, a significant increase in post-treatment HDL (p = 0.019) and
apolipoprotein A1 (p = 0.012) but a decrease in HOMA-IR (p = 0.04), C-peptide (p
= 0.019) and hemoglobin A1c (p = 0.047) were found in patients with baseline IR;
a significant increase in HOMA-IR (p = 0.002) was found in patients without
baseline IR. The latter change was observed only in G1 (p = 0.01) but not G2
patients. Although the pre-treatment metabolic profiles of G1 and G2 patients
were indifferent, G1 had higher post-treatment triglyceride/HDL ratios (p =
0.041) and triglyceride (p = 0.044) levels than G2 patients. CONCLUSIONS: G2
benefit more than G1 patients from viral clearance in metabolic alterations,
particularly in those without baseline IR.
PMID- 25122117
TI - The role of transapical cannulation in the operative management of acute aortic
dissection.
AB - OBJECTIVES: The aim of the study was to investigate the usefulness of transapical
cannulation as the routine cannulation site in patients with acute aortic
dissection and to compare it with other cannulation methods. METHODS: Between
January 2010 and December 2013, emergency surgery was performed in 111
consecutive patients with acute type A aortic dissection. Patients were divided
into two groups: transapical cannulation group and other cannulation sites group
(including femoral and axillary artery cannulation). Pre-, intra- and
postoperative data were compared between these two groups of patients. RESULTS:
Transapical cannulation was the most frequent cannulation site (78 patients,
70.3%), the femoral artery was selected in 24 patients (21.6%) and the axillary
artery in 9 patients (8.1%). The mortality rate in the transapical group was
16.7% and 18.2% when other cannulation sites were chosen (p=0.85). No difference
in postoperative stroke rate (6.4% vs 9.1%, p=0.62, transapical vs other
cannulation sites group, respectively), myocardial infarction (6.4% vs 6.1%,
p=0.94) and postoperative acute renal insufficiency incidence (9% vs 6.1%,
p=0.61) was found. CONCLUSIONS: Routine transapical cannulation in patients with
acute type A aortic dissection is a fast and safe way to establish
cardiopulmonary bypass. There is no difference in major operative outcomes after
transapical cannulation when compared to the other cannulation sites.
PMID- 25122119
TI - Modeling development in retinal afferents: retinotopy, segregation, and
ephrinA/EphA mutants.
AB - During neural development, neurons extend axons to target areas of the brain.
Through processes of growth, branching and retraction these axons establish
stereotypic patterns of connectivity. In the visual system, these patterns
include retinotopic organization and the segregation of individual axons onto
different subsets of target neurons based on the eye of origin (ocular dominance)
or receptive field type (ON or OFF). Characteristic disruptions to these patterns
occur when neural activity or guidance molecule expression is perturbed. In this
paper we present a model that explains how these developmental patterns might
emerge as a result of the coordinated growth and retraction of individual axons
and synapses responding to position-specific markers, trophic factors and
spontaneous neural activity. This model derives from one presented earlier
(Godfrey et al., 2009) but which is here extended to account for a wider range of
phenomena than previously described. These include ocular dominance and ON-OFF
segregation and the results of altered ephrinA and EphA guidance molecule
expression. The model takes into account molecular guidance factors, realistic
patterns of spontaneous retinal wave activity, trophic molecules, homeostatic
mechanisms, axon branching and retraction rules and intra-axonal signaling
mechanisms that contribute to the survival of nearby synapses on an axon. We show
that, collectively, these mechanisms can account for a wider range of phenomena
than previous models of retino-tectal development.
PMID- 25122120
TI - Genetic deletion of SEPT7 reveals a cell type-specific role of septins in
microtubule destabilization for the completion of cytokinesis.
AB - Cytokinesis terminates mitosis, resulting in separation of the two sister cells.
Septins, a conserved family of GTP-binding cytoskeletal proteins, are an absolute
requirement for cytokinesis in budding yeast. We demonstrate that septin
dependence of mammalian cytokinesis differs greatly between cell types: genetic
loss of the pivotal septin subunit SEPT7 in vivo reveals that septins are
indispensable for cytokinesis in fibroblasts, but expendable in cells of the
hematopoietic system. SEPT7-deficient mouse embryos fail to gastrulate, and
septin-deficient fibroblasts exhibit pleiotropic defects in the major cytokinetic
machinery, including hyperacetylation/stabilization of microtubules and stalled
midbody abscission, leading to constitutive multinucleation. We identified the
microtubule depolymerizing protein stathmin as a key molecule aiding in septin
independent cytokinesis, demonstrated that stathmin supplementation is sufficient
to override cytokinesis failure in SEPT7-null fibroblasts, and that knockdown of
stathmin makes proliferation of a hematopoietic cell line sensitive to the septin
inhibitor forchlorfenuron. Identification of septin-independent cytokinesis in
the hematopoietic system could serve as a key to identify solid tumor-specific
molecular targets for inhibition of cell proliferation.
PMID- 25122122
TI - Unraveling the interplay of backbone rigidity and electron rich side-chains on
electron transfer in peptides: the realization of tunable molecular wires.
AB - Electrochemical studies are reported on a series of peptides constrained into
either a 310-helix (1-6) or beta-strand (7-9) conformation, with variable numbers
of electron rich alkene containing side chains. Peptides (1 and 2) and (7 and 8)
are further constrained into these geometries with a suitable side chain tether
introduced by ring closing metathesis (RCM). Peptides 1, 4 and 5, each containing
a single alkene side chain reveal a direct link between backbone rigidity and
electron transfer, in isolation from any effects due to the electronic properties
of the electron rich side-chains. Further studies on the linear peptides 3-6
confirm the ability of the alkene to facilitate electron transfer through the
peptide. A comparison of the electrochemical data for the unsaturated tethered
peptides (1 and 7) and saturated tethered peptides (2 and 8) reveals an interplay
between backbone rigidity and effects arising from the electron rich alkene side
chains on electron transfer. Theoretical calculations on beta-strand models
analogous to 7, 8 and 9 provide further insights into the relative roles of
backbone rigidity and electron rich side-chains on intramolecular electron
transfer. Furthermore, electron population analysis confirms the role of the
alkene as a "stepping stone" for electron transfer. These findings provide a new
approach for fine-tuning the electronic properties of peptides by controlling
backbone rigidity, and through the inclusion of electron rich side-chains. This
allows for manipulation of energy barriers and hence conductance in peptides, a
crucial step in the design and fabrication of molecular-based electronic devices.
PMID- 25122121
TI - Efficacy and safety of praziquantel, tribendimidine and mebendazole in patients
with co-infection of Clonorchis sinensis and other helminths.
AB - BACKGROUND: Both tribendimidine and mebendazole are broad-spectrum drugs for anti
intestinal nematodes. We aim to assess the efficacy and safety of tribendimidine
and mebendazole in patients with co-infection of Clonorchis sinensis and other
helminths. METHOD: We performed a randomized open-label trial in Qiyang, People's
Republic of China. Eligible participants were randomly assigned to one of four
groups: (i) a single dose of 400 mg tribendimidine, (ii) 200 mg tribendimidine
twice daily, (iii) 75 mg/kg praziquantel divided in four doses within 2 days, and
(iv) a single dose of 400 mg mebendazole. Cure rates and egg reduction rates were
assessed, and adverse events were monitored after treatments. Uncured patients
accepted the second treatment with the same drugs after the first treatment.
RESULTS: 156 patients were eligible for the study. Results from the first
treatment showed that the cure rates of single-dose tribendimidine and
praziquantel against C. sinensis were 50% and 56.8%, respectively; the single
dose tribendimidine achieved the cure rate of 77.8% in the treatment for
hookworm, which was significantly higher than that of praziquantel; Low cure
rates were obtained in the treatment of single-dose tribendimidine against
Ascaris lumbricoides and Trichuris trichiura (28.6% and 23.1%). Results of the
second treatment illustrated the cure rates of tribendimidine and praziquantel
against C. sinensis were 78.1% and 75%, respectively. Most adverse events were
mild and transient. Adverse events caused by tribendimidine were significantly
less than praziquantel. CONCLUSION: Single-dose tribendimidine showed similar
efficacy against C. sinensis as praziquantel with less adverse events, and
achieved significantly higher cure rate in the treatment for hookworm than those
of praziquantel and mebendazole. Low cure rates, which were still higher than
other drugs, were obtained in the treatment of single-dose tribendimidine against
Ascaris lumbricoides and Trichuris trichiura. TRIAL REGISTRATION: Controlled
Trials.com ISRCTN55086560.
PMID- 25122123
TI - The frequency and determinants of liver stiffness measurement failure: a
retrospective study of "real-life" 38,464 examinations.
AB - OBJECTIVE: To investigate the frequency and determinants of liver stiffness
measurement (LSM) failure by means of FibroScan in "real-life" Chinese patients.
METHODS: A total of 38,464 "real-life" Chinese patients in 302 military hospital
of China through the whole year of 2013, including asymptomatic carrier, chronic
hepatitis B, chronic hepatitis C, liver cirrhosis (LC), alcoholic liver disease,
autoimmune liver disease, hepatocellular carcinoma (HCC) and other, were
enrolled, their clinical and biological parameters were retrospectively
investigated. Liver fibrosis was evaluated by FibroScan detection. S probe (for
children with height less than 1.20 m) and M probe (for adults) were used. LSM
failure defined as zero valid shots (unsuccessful LSM), or the ratio of the
interquartile range to the median of 10 measurements (IQR/M) greater than 0.30
plus median LSM greater or equal to 7.1 kPa (unreliable LSM). RESULTS: LSM
failure occurred in 3.34% of all examinations (1286 patients out of 38,464),
among them, there were 958 cases (2.49%) with unsuccessful LSM, and 328 patients
(0.85%) with unreliable LSM. Statistical analyses showed that LSM failure was
independently associated with body mass index (BMI) greater than 30 kg/m(2),
female sex, age greater than 50 years, intercostal spaces (IS) less than 9 mm,
decompensated liver cirrhosis and HCC patients. There were no significant
differences among other diseases. By changing another skilled operator, success
was achieved on 301 cases out of 1286, which reduced the failure rate to 2.56%,
the decrease was significant (P<0.0001). CONCLUSIONS: The principal reasons of
LSM failure are ascites, obesity and narrow of IS. The failure rates of HCC,
decompensated LC, elder or female patients are higher. These results emphasize
the need for adequate operator training, technological improvements and optimal
criteria for specific patient subpopulations.
PMID- 25122125
TI - Drug-pathway interaction prediction via multiple feature fusion.
AB - Predicting new drug-pathway interactions from heterogeneous biological data is
important not only for the understanding of various drug response and molecular
interaction processes, but also for the development of novel drugs and the
therapy of human diseases. In this paper, three different learning methods
including the Bipartite Local Models method (BLM), Gaussian Interaction Profiles
kernels (GIP) method and Graph-based Semi-supervised Learning method (GBSSL) were
used to predict drug-pathway interactions. To realize the purpose, drugs were
firstly represented by functional groups and chemical structure similarity, and
pathways were represented by their related gene expressions and semantic
similarity based features. Then, the parameter optimization procedures were
further adopted to deal with heterogeneous data sources. As a result, the
proposed methods achieved a high ROC curve score (AUC score) over 0.95, which
validated the effectiveness of multiple information integration. Moreover,
several new potential drug-pathway interactions were identified for further
biological function research.
PMID- 25122124
TI - Snail promotes epithelial mesenchymal transition in breast cancer cells in part
via activation of nuclear ERK2.
AB - Snail transcription factor is up-regulated in several cancers and associated with
increased tumor migration and invasion via induction of epithelial-to-mesenchymal
transition (EMT). MAPK (ERK1/2) signaling regulates cellular processes including
cell motility, adhesion, and invasion. We investigated the regulation of ERK1/2
by Snail in breast cancer cells. ERK1/2 activity (p-ERK) was higher in breast
cancer patient tissue as compared to normal tissue. Snail and p-ERK were
increased in several breast cancer cell lines as compared to normal mammary
epithelial cells. Snail knockdown in MDA-MB-231 and T47-D breast cancer cells
decreased or re-localized p-ERK from the nuclear compartment to the cytoplasm.
Snail overexpression in MCF-7 breast cancer cells induced EMT, increased cell
migration, decreased cell adhesion and also increased tumorigenicity. Snail
induced nuclear translocation of p-ERK, and the activation of its subcellular
downstream effector, Elk-1. Inhibiting MAPK activity with UO126 or knockdown of
ERK2 isoform with siRNA in MCF-7 Snail cells reverted EMT induced by Snail as
shown by decreased Snail and vimentin expression, decreased cell migration and
increased cell adhesion. Overall, our data suggest that ERK2 isoform activation
by Snail in aggressive breast cancer cells leads to EMT associated with increased
cell migration and decreased cell adhesion. This regulation is enhanced by
positive feedback regulation of Snail by ERK2. Therefore, therapeutic targeting
of ERK2 isoform may be beneficial for breast cancer.
PMID- 25122126
TI - Disrupted TH17/Treg balance in patients with chronic low back pain.
AB - Chronic low back pain (CLBP) is a leading cause of disability and costs in health
care systems worldwide. Despite extensive research, the exact pathogenesis of
CLBP, particularly the individual risk of chronification remains unclear. To
investigate a possible role of the adaptive immune system in the pathophysiology
of CLBP, we analyzed T cell related cytokine profiles, T cell related mRNA
expression patterns and the distribution of T cell subsets in 37 patients
suffering from nonspecific CLBP before and after multimodal therapy in comparison
to 25 healthy controls. Serum patterns of marker cytokines were analyzed by
Luminex technology, mRNA expression of cytokines and specific transcription
factors was measured by real-time PCR, and distribution of TH1-, TH2-, TH17- and
regulatory T cell (Tregs) subsets was determined by multicolor flow cytometry. We
found that CLBP patients exhibit an increased number of anti-inflammatory Tregs,
while pro-inflammatory TH17 cells are decreased, resulting in an altered
TH17/Treg ratio. Accordingly, FoxP3 and TGF-beta-mRNA expression was elevated,
while expression of IL-23 was reduced. Serum cytokine analyses proved to be
unsuitable to monitor the adaptive immune response in CLBP patients. We further
show that even after successful therapy with lasting reduction of pain, T cell
subset patterns remained altered after a follow-up period of 6 months. These
findings suggest an involvement of TH17/Treg cells in the pathogenesis of CLBP
and emphasize the importance of these cells in the crosstalk of pain and immune
response. TRIAL REGISTRATION: German Clinical Trial Register: Registration Trial
DRKS00005954.
PMID- 25122128
TI - Examination of the Relationship Between Hopelessness Levels and Coping Strategies
Among the Family Caregivers of Patients With Cancer.
AB - BACKGROUND: Family caregivers who provide care for cancer patients may have to
cope with a variety of physical, social, and economic problems during the
caregiving process. A sense of hopelessness seems to lead to increasingly
negative evaluations of new situations and less effective coping strategies.
OBJECTIVE: The objective of the study was to examine the relationship between
hopelessness and the coping strategies of the family caregivers of oncology
patients. METHODS: This cross-sectional, descriptive correlational design study
was carried out in the adult oncology unit and outpatient radiation oncology
units of a university hospital in Turkey. The research sample was composed of 110
family caregivers. A sociodemographic data form, the Coping Stress Strategies
Scale, and the Beck Hopelessness Scale were used in face-to-face interviews.
RESULTS: Significant correlations were found between hopelessness and coping
strategies. There was a positive correlation between hopelessness and the
helpless approaches, which constitute a part of the emotion-focused coping
strategies (r = 0.254, P < .01). There was a negative correlation between
hopelessness and problem-focused coping strategies (optimistic approach and
seeking social support) (r = -0.484, P < .01; r = -0.190, P < .05). CONCLUSION:
In our study, we found that when the hopes of family caregivers are raised, they
may adopt a more optimistic approach, and seek more social support, and display
more effective coping strategies. IMPLICATIONS FOR PRACTICE: This study could be
used to help develop nursing interventions and efficient coping strategies. It
suggests how oncology nurses may support family caregivers to increase their
level of hope.
PMID- 25122127
TI - Genomic distribution of H3K9me2 and DNA methylation in a maize genome.
AB - DNA methylation and dimethylation of lysine 9 of histone H3 (H3K9me2) are two
chromatin modifications that can be associated with gene expression or
recombination rate. The maize genome provides a complex landscape of interspersed
genes and transposons. The genome-wide distribution of DNA methylation and
H3K9me2 were investigated in seedling tissue for the maize inbred B73 and
compared to patterns of these modifications observed in Arabidopsis thaliana.
Most maize transposons are highly enriched for DNA methylation in CG and CHG
contexts and for H3K9me2. In contrast to findings in Arabidopsis, maize CHH
levels in transposons are generally low but some sub-families of transposons are
enriched for CHH methylation and these families exhibit low levels of H3K9me2.
The profile of modifications over genes reveals that DNA methylation and H3K9me2
is quite low near the beginning and end of genes. Although elevated CG and CHG
methylation are found within gene bodies, CHH and H3K9me2 remain low. Maize has
much higher levels of CHG methylation within gene bodies than observed in
Arabidopsis and this is partially attributable to the presence of transposons
within introns for some maize genes. These transposons are associated with high
levels of CHG methylation and H3K9me2 but do not appear to prevent
transcriptional elongation. Although the general trend is for a strong depletion
of H3K9me2 and CHG near the transcription start site there are some putative
genes that have high levels of these chromatin modifications. This study provides
a clear view of the relationship between DNA methylation and H3K9me2 in the maize
genome and how the distribution of these modifications is shaped by the interplay
of genes and transposons.
PMID- 25122129
TI - Community Nursing Care of Chinese-Australian Cancer Patients: A Qualitative
Study.
AB - BACKGROUND: Providing quality care and support to cancer patients from minority
cultures can challenge community nurses when language barriers and cultural
complexities intersect with the need for complex care. OBJECTIVES: This article
reports on a qualitative study that explores interactions between community
nurses and Chinese-Australian cancer patients. METHODS: The research method
focused on particular nurse-patient encounters and involved preencounter and
postencounter interviews with the nurse, postencounter interviews with the
patient, and observation of the encounters. Participants included community
nurses, Chinese cancer patients being cared for at home, and their carers if
present. RESULTS: Four themes were conceptualized: (1) the impact of language
barriers on nurse-patient interactions, (2) patient understandings of the scope
and objectives of healthcare services, (3) cultural complexities and
sensitivities, and (4) valued care and support. The study demonstrates that,
although many nurses do provide comprehensive, culturally competent care,
language barriers can lead to task-oriented rather than comprehensive approaches,
and other cultural complexities do have an impact on patient experiences and on
the quality of nurse-patient interactions. Nevertheless, most patient
participants experienced a feeling of security as a result of regular contact
with a community nursing service. CONCLUSION: Cancer patients with complex care
needs but limited English proficiency require support to negotiate complicated
community services networks. Culturally competent community nurses can provide
this support. IMPLICATIONS FOR PRACTICE: The study highlights the need for
continuing cultural competence education for community nurses and the importance
of careful discharge planning to ensure continuity of care for this vulnerable
patient group.
PMID- 25122131
TI - Social Cultural Influences on Breast Cancer Views and Breast Health Practices
Among Chinese Women in the United Kingdom.
AB - BACKGROUND: Incidence rates for breast cancer have increased significantly among
Chinese women, accompanied by low utilization of breast screening and delay in
symptom presentation. OBJECTIVE: The aims of this study were to explore (1) views
on breast cancer and breast health among Chinese women in the United Kingdom and
(2) the potential influence of social and cultural context on views and screening
behavior. METHODS: Qualitative interviews were carried out with 22 Chinese women.
Pertinent aspects of Grounded Theory methods, including simultaneous data
collection and analysis, constant comparison, and memo writing, were used.
RESULTS: Four themes emerged: cultural views on breast cancer, information
sources and knowledge, breast screening practice, and views on healthcare
services. The theme views on breast cancer had 3 subthemes: a fearful disease,
taboo, and fatalism. Aspects of traditional Chinese culture had important
influences on Chinese women's views on breast cancer. Self-care formed the most
significant strategy to promote health and prevent illness. Although the study
found high utilization of breast screening when offered, only 6 women reported
breast awareness practices. CONCLUSIONS: This study found that traditional
beliefs were not the sole determinant of breast health behavior. The way in which
breast screening services are offered in the United Kingdom may reduce the
significance of cultural views and shape individuals' health behavior.
IMPLICATIONS FOR PRACTICE: Findings indicate that information on breast awareness
should be delivered to this group of women in Chinese by health professionals
through Chinese mass media.
PMID- 25122130
TI - Effects of a Randomized Controlled Trial to Increase Repeat Mammography Screening
in Iranian Women.
AB - BACKGROUND: Although mammography use has increased in developed countries,
regular screening in developing countries including Iran remains low. Multiple
frameworks, including the Health Belief Model (HBM) and the Theory of Planned
Behavior (TPB), have been used to understand screening practices among Iranians.
The HBM includes intrapersonal constructs such as perceptions of breast cancer
and mammography. The TPB includes interpersonal and environmental constructs,
such as perceived control and subjective norms. OBJECTIVES: The current study had
2 objectives: (1) to examine changes in the HBM and TPB constructs and repeat
mammography screening in women receiving either intervention and women in the
control group and (2) to compare changes in the HBM and TPB constructs and repeat
mammography screening across the 2 interventions. METHODS: One hundred eight-four
women from 3 randomly selected health centers in Sanandaj, Iran, participated.
Eligibility criteria were being 50 years or older, having received a mammogram in
the past 2 to 3 years, and no intention to obtain a mammogram within the next
year. RESULTS: The TPB and HBM participants exhibited greater changes in the HBM
and TPB constructs and were more likely to have a mammogram relative to control
participants. The TPB and HBM participants exhibited comparable changes in
constructs and repeat mammography. CONCLUSION: Findings suggest both
interventions equally improved mammography screening. Additional studies are
furthermore warranted to address nonadherent Iranian women's needs in line with
these conceptual models. IMPLICATIONS FOR PRACTICE: Use of the HBM and TPB
constructs in clinical practice may be helpful to promote continued screening
among this population.
PMID- 25122133
TI - Ways of coping with stress and perceived social support in gynecologic cancer
patients.
AB - BACKGROUND: Stress is commonly encountered among cancer patients and may be a
challenge affecting immune system resistance. Social support may contribute
positively to the health of cancer patients, playing a role in coping with
stress. OBJECTIVE: The aim of this study was to determine whether ways of coping
are related to social support given to women with gynecologic cancer. METHODS:
The study was performed as a cross-sectional design in a university hospital in
Istanbul, Turkey, with 221 women with gynecologic cancer; the data were collected
via 3 questionnaires, the first with sociodemographic and clinical features, the
second with multidimensional scale of perceived social support, and the third
with the scale of ways of coping with stress. RESULTS: Women with gynecologic
cancer who were employed and declared their incomes as balanced and reported more
years of education were more likely to perceive higher social support and to use
the ineffective coping ways with stress at a lower rate (P < .05) than other
participants. Based on correlational analysis, effective coping ways with stress
increase as perceived social support from family, friends, significant other, and
total increases (P < .05). CONCLUSIONS: Social support from family members is the
mainstay of coping with stress by women with gynecologic cancer. IMPLICATIONS FOR
PRACTICE: Nurses are indispensable in increasing social support required by women
with gynecologic cancer. Well-trained clinical nurses via in-service programs
should be experienced and aware of women diagnosed with gynecologic cancer in
need of social support during hospital visits and provide necessary guidance.
PMID- 25122132
TI - Gender and Role Differences in Couples' Communication During Cancer Survivorship.
AB - BACKGROUND: Individuals with cancer and their partners often experience
communication difficulties. However, questions still remain regarding the
influence of gender and role in cancer survivor-partner communication within
couples. OBJECTIVE: The current study intended to examine the communication
patterns in breast, colorectal, and prostate cancer survivor-partner couples
during cancer survivorship and whether gender and role differences in couples
communication exist. METHODS: The dominant-less dominant method of sequential
mixed design was used. Ten couples who were recruited from the University
Hospital registry in Cleveland, Ohio, participated in both mail surveys and
individual interviews. Family and cancer-related communication was assessed in
the quantitative phase. RESULTS: Both male survivors and partners demonstrated
better family communication scores compared with their female counterparts,
whereas there were no gender differences in the cancer-related communication
scores. In the qualitative phase, 3 major themes were identified: (1) selective
sharing of cancer-related issues, (2) initiation of cancer-related communication,
and (3) emotional reaction in communication. The patterns associated with these
themes differed between the male survivor-female partner and female survivor-male
partner couples. CONCLUSIONS: This study provides new knowledge about family and
cancer-related communication. Our findings highlight the importance of
understanding different perspectives in the quality of communication by gender
and role. IMPLICATIONS FOR PRACTICE: Exploring couples' communication patterns by
gender and role stimulates the research and the development of effective consumer
centered communication interventions. The findings provide assessment tools to
inform dyadic communication patterns for clinical and scientific purposes.
PMID- 25122134
TI - Patients With Hepatocellular Carcinoma Near the End of Life: A Longitudinal
Qualitative Study of Their Illness Experiences.
AB - BACKGROUND: In the United States, the incidence of hepatocellular carcinoma (HCC)
is rising. For those diagnosed with terminal HCC, there is no curative treatment
and duration of survival is typically 1 to 2 years. Research on illness and
treatment experiences toward the end of life for patients with terminal HCC is
limited. OBJECTIVE: The aim of this study was to explore the illness experiences
of patients with terminal HCC as they approached the end of life. METHODS: This
study used a prospective, longitudinal descriptive design. Interview data were
collected from 14 patients once a month for up to 6 months, for a total of 45
interviews. Data were analyzed using conventional content analysis. RESULTS:
Three major themes (illness perceptions, decision to start treatment, and
navigating treatment over time) and 10 subthemes were identified that were
reflected across time in all patient experiences. Patients faced challenges with
symptom experiences, treatment decisions, and unmet information needs affecting
their quality of life. CONCLUSIONS: Gaining knowledge about the challenges facing
patients with HCC is crucial for designing interventions that optimize their
quality of life. IMPLICATIONS FOR PRACTICE: Healthcare professionals may improve
the quality of life of patients with terminal HCC by eliciting patients'
perceptions of their illness and treatment decisions, symptom experiences, and
information needs as the disease progresses and providing symptom management and
offering information tailored to their needs. Care for patients with HCC who are
approaching the end of life should be multidisciplinary and include timely
referral to palliative care.
PMID- 25122138
TI - Model study of the pressure build-up during subcutaneous injection.
AB - In this study we estimate the subcutaneous tissue counter pressure during drug
infusion from a series of injections of insulin in type 2 diabetic patients using
a non-invasive method. We construct a model for the pressure evolution in
subcutaneous tissue based on mass continuity and the flow laws of a porous
medium. For equivalent injection forces we measure the change in the infusion
rate between injections in air at atmospheric pressure and in tissue. From a best
fit with our model, we then determine the flow permeability as well as the bulk
modulus of the tissue, estimated to be of the order 10-11-10-10 m2 and 105 Pa,
respectively. The permeability is in good agreement with reported values for
adipose porcine tissue. We suggest our model as a general way to estimate the
pressure build-up in tissue during subcutaneous injection.
PMID- 25122137
TI - Alteration of skin wound healing in keratinocyte-specific mediator complex
subunit 1 null mice.
AB - MED1 (Mediator complex subunit 1) is a co-activator of various transcription
factors that function in multiple transcriptional pathways. We have already
established keratinocyte-specific MED1 null mice (Med1(epi-/-)) that develop
epidermal hyperplasia. Herein, to investigate the function(s) of MED1 in skin
wound healing, full-thickness skin wounds were generated in Med1(epi-/-) and age
matched wild-type mice and the healing process was analyzed. Macroscopic wound
closure and the re-epithelialization rate were accelerated in 8-week-old Med1(epi
/-) mice compared with age-matched wild-type mice. Increased lengths of migrating
epithelial tongues and numbers of Ki67-positive cells at the wounded epidermis
were observed in 8-week-old Med1(epi-/-) mice, whereas wound contraction and the
area of alpha-SMA-positive myofibroblasts in the granulation tissue were
unaffected. Migration was enhanced in Med1(epi-/-) keratinocytes compared with
wild-type keratinocytes in vitro. Immunoblotting revealed that the expression of
follistatin was significantly decreased in Med1(epi-/-) keratinocytes. Moreover,
the mitogen-activated protein kinase pathway was enhanced before and after
treatment of Med1(epi-/-) keratinocytes with activin A in vitro. Cell-cycle
analysis showed an increased ratio of S phase cells after activin A treatment of
Med1(epi-/-) keratinocytes compared with wild-type keratinocytes. These findings
indicate that the activin-follistatin system is involved in this acceleration of
skin wound healing in 8-week-old Med1(epi-/-) mice. On the other hand, skin wound
healing in 6-month-old Med1(epi-/-) mice was significantly delayed with decreased
numbers of Ki67-positive cells at the wounded epidermis as well as BrdU-positive
label retaining cells in hair follicles compared with age-matched wild-type mice.
These results agree with our previous observation that hair follicle bulge stem
cells are reduced in older Med1(epi-/-) mice, indicating a decreased contribution
of hair follicle stem cells to epidermal regeneration after wounding in 6-month
old Med1(epi-/-) mice. This study sheds light on the novel function of MED1 in
keratinocytes and suggests a possible new therapeutic approach for skin wound
healing and aging.
PMID- 25122139
TI - Increased platelet reactivity is associated with circulating platelet-monocyte
complexes and macrophages in human atherosclerotic plaques.
AB - OBJECTIVE: Platelet reactivity, platelet binding to monocytes and monocyte
infiltration play a detrimental role in atherosclerotic plaque progression. We
investigated whether platelet reactivity was associated with levels of
circulating platelet-monocyte complexes (PMCs) and macrophages in human
atherosclerotic carotid plaques. METHODS: Platelet reactivity was determined by
measuring platelet P-selectin expression after platelet stimulation with
increasing concentrations of adenosine diphosphate (ADP), in two independent
cohorts: the Circulating Cells cohort (n = 244) and the Athero-Express cohort (n
= 91). Levels of PMCs were assessed by flow cytometry in blood samples of
patients who were scheduled for percutaneous coronary intervention (Circulating
Cells cohort). Monocyte infiltration was semi-quantitatively determined by
histological examination of atherosclerotic carotid plaques collected during
carotid endarterectomy (Athero-Express cohort). RESULTS: We found increased
platelet reactivity in patients with high PMCs as compared to patients with low
PMCs (median (interquartile range): 4153 (1585-11267) area under the curve (AUC)
vs. 9633 (3580-21565) AUC, P<0.001). Also, we observed increased platelet
reactivity in patients with high macrophage levels in atherosclerotic plaques as
compared to patients with low macrophage levels in atherosclerotic plaques (mean
+/- SD; 8969 +/- 3485 AUC vs. 7020 +/- 3442 AUC, P = 0.02). All associations
remained significant after adjustment for age, sex and use of drugs against
platelet activation. CONCLUSION: Platelet reactivity towards ADP is associated
with levels of PMCs and macrophages in human atherosclerotic carotid plaques.
PMID- 25122140
TI - Construction and validation of a regulatory network for pluripotency and self
renewal of mouse embryonic stem cells.
AB - A 30-node signed and directed network responsible for self-renewal and
pluripotency of mouse embryonic stem cells (mESCs) was extracted from several
ChIP-Seq and knockdown followed by expression prior studies. The underlying
regulatory logic among network components was then learned using the initial
network topology and single cell gene expression measurements from mESCs cultured
in serum/LIF or serum-free 2i/LIF conditions. Comparing the learned network
regulatory logic derived from cells cultured in serum/LIF vs. 2i/LIF revealed
differential roles for Nanog, Oct4/Pou5f1, Sox2, Esrrb and Tcf3. Overall, gene
expression in the serum/LIF condition was more variable than in the 2i/LIF but
mostly consistent across the two conditions. Expression levels for most genes in
single cells were bimodal across the entire population and this motivated a
Boolean modeling approach. In silico predictions derived from removal of nodes
from the Boolean dynamical model were validated with experimental single and
combinatorial RNA interference (RNAi) knockdowns of selected network components.
Quantitative post-RNAi expression level measurements of remaining network
components showed good agreement with the in silico predictions. Computational
removal of nodes from the Boolean network model was also used to predict lineage
specification outcomes. In summary, data integration, modeling, and targeted
experiments were used to improve our understanding of the regulatory topology
that controls mESC fate decisions as well as to develop robust directed lineage
specification protocols.
PMID- 25122142
TI - Making biomolecular simulations accessible in the post-Nobel Prize era.
PMID- 25122135
TI - Small molecule adenosine 5'-monophosphate activated protein kinase (AMPK)
modulators and human diseases.
AB - Adenosine 5'-monophosphate activated protein kinase (AMPK) is a master sensor of
cellular energy status that plays a key role in the regulation of whole-body
energy homeostasis. AMPK is a serine/threonine kinase that is activated by
upstream kinases LKB1, CaMKKbeta, and Tak1, among others. AMPK exists as
alphabetagamma trimeric complexes that are allosterically regulated by AMP, ADP,
and ATP. Dysregulation of AMPK has been implicated in a number of metabolic
diseases including type 2 diabetes mellitus and obesity. Recent studies have
associated roles of AMPK with the development of cancer and neurological
disorders, making it a potential therapeutic target to treat human diseases. This
review focuses on the structure and function of AMPK, its role in human diseases,
and its direct substrates and provides a brief synopsis of key AMPK modulators
and their relevance in human diseases.
PMID- 25122141
TI - Inhibition of the TRAIL death receptor by CMV reveals its importance in NK cell
mediated antiviral defense.
AB - TNF-related apoptosis inducing ligand (TRAIL) death receptors (DR) regulate
apoptosis and inflammation, but their role in antiviral defense is poorly
understood. Cytomegaloviruses (CMV) encode many immune-modulatory genes that
shape host immunity, and they utilize multiple strategies to target the TNF
family cytokines. Here we show that the m166 open reading frame (orf) of mouse
CMV (MCMV) is strictly required to inhibit expression of TRAIL-DR in infected
cells. An MCMV mutant lacking m166 expression (m166stop) is severely compromised
for replication in vivo, most notably in the liver, and depleting natural killer
(NK) cells, or infecting TRAIL-DR-/- mice, restored MCMV-m166stop replication
completely. These results highlight the critical importance for CMV to have
evolved a strategy to inhibit TRAIL-DR signaling to thwart NK-mediated defenses.
PMID- 25122143
TI - Comprehensive CFTR gene analysis of the French cystic fibrosis screened newborn
cohort: implications for diagnosis, genetic counseling, and mutation-specific
therapy.
AB - PURPOSE: Newborn screening (NBS) for cystic fibrosis (CF) was implemented
throughout France in 2002. It involves a four-tiered procedure: immunoreactive
trypsin (IRT)/DNA/IRT/sweat test [corrected] was implemented throughout France in
2002. The aim of this study was to assess the performance of molecular CFTR gene
analysis from the French NBS cohort, to evaluate CF incidence, mutation detection
rate, and allelic heterogeneity. METHODS: During the 8-year period, 5,947,148
newborns were screened for cystic fibrosis. The data were collected by the
Association Francaise pour le Depistage et la Prevention des Handicaps de
l'Enfant. The mutations identified were classified into four groups based on
their potential for causing disease, and a diagnostic algorithm was proposed.
RESULTS: Combining the genetic and sweat test results, 1,160 neonates were
diagnosed as having cystic fibrosis. The corresponding incidence, including both
the meconium ileus (MI) and false-negative cases, was calculated at 1 in 4,726
live births. The CF30 kit, completed with a comprehensive CFTR gene analysis,
provides an excellent detection rate of 99.77% for the mutated alleles, enabling
the identification of a complete genotype in 99.55% of affected neonates. With
more than 200 different mutations characterized, we confirmed the French allelic
heterogeneity. CONCLUSION: The very good sensitivity, specificity, and positive
predictive value obtained suggest that the four-tiered IRT/DNA/IRT/sweat test
procedure may provide an effective strategy for newborn screening for cystic
fibrosis.
PMID- 25122146
TI - Feasibility study to quantify the auditory and social environment of older adults
using a digital language processor.
AB - OBJECTIVE: To investigate the feasibility of using a digital language processor
(DLP) to objectively quantify the auditory and social environment of older
adults. DESIGN: Thirty-seven participants aged 64 to 91 years residing in a
retirement community were asked to wear a DLP to record their auditory and
language environment during 1 waking day. Recordings were analyzed with
specialized software to derive quantitative estimates such as the number of
spoken words heard and percentage of time spent around meaningful speech versus
television/radio. RESULTS: Adequate DLP recordings that began before 10 AM and
lasted for 10 hours or greater were collected from 24 participants. The mean
duration of recording was 13 hours and 13 minutes, and individuals spent a mean
of 26.7% (range, 4%-58%) of their waking day near a television or other
electronic sounds. The projected mean word count over a maximum of 16 hours was
33,141 with nearly a 14-fold range between the lowest and highest observed values
(range, 5120-77,882). CONCLUSIONS: High-quality objective data on the auditory
environment of older adults can be feasibly measured with the DLP. Findings from
this study may guide future studies investigating auditory and language outcomes
in older adults.
PMID- 25122147
TI - Influence of laser-assisted cochleostomy on acoustically evoked compound action
potentials in the guinea pig.
AB - HYPOTHESIS: Making a cochleostomy with a laser can affect the inner ear function.
BACKGROUND: Different types of lasers can be used to create a fenestration in the
footplate of the stapes during stapedotomy. Because of variations in absorption
spectra of the laser light in various tissues or fluids, each laser has its own
characteristics and possible side effects. MATERIALS AND METHODS: The basal turns
of the cochleae of 20 guinea pigs were fenestrated using 4 types of lasers
(thulium, KTP, CO2, diode; all groups n = 4). A control group (n = 4) was
included to correct for the effects of the surgery alone. At 3 different time
points, acoustically evoked compound action potentials (CAPs) were recorded at 5
frequencies and at different sound pressure levels. N1-P2 amplitudes were
measured, and subsequently, thresholds were calculated. A repeated measures
analysis of variance was used to investigate differences between groups. RESULTS:
There was a decrease in CAP amplitudes and an increase in CAP thresholds after
cochleostomy with each laser. The increase in thresholds was significantly larger
for higher frequencies. The thulium laser evoked the largest threshold shifts,
the KTP laser the smallest with the CO2, and diode lasers in intermediate
positions. Overall, there was an increase in latencies after treatment.
CONCLUSION: Laser treatment on or near the cochlea can cause damage to the
sensitivity of the cochlea for sound. The thulium laser seems to be the worst
choice in this respect.
PMID- 25122145
TI - Early-onset autosomal recessive cerebellar ataxia associated with retinal
dystrophy: new human hotfoot phenotype caused by homozygous GRID2 deletion.
AB - PURPOSE: The aim of this study was to identify the genetic cause of early-onset
autosomal recessive cerebellar ataxia associated with retinal dystrophy in a
consanguineous family. METHODS: An affected 6-month-old child underwent
neurological and ophthalmological examinations. Genetic analyses included
homozygosity mapping, copy number analysis, conventional polymerase chain
reaction, Sanger sequencing, quantitative polymerase chain reaction, and whole
exome sequencing. Expression analysis of GRID2 was performed by quantitative
polymerase chain reaction and immunohistochemistry. RESULTS: A homozygous
deletion of exon 2 of GRID2 (p.Gly30_Glu81del) was identified in the proband.
GRID2 encodes an ionotropic glutamate receptor known to be selectively expressed
in cerebellar Purkinje cells. Here, we demonstrated GRID2 expression in human
adult retina and retinal pigment epithelium. In addition, Grid2 expression was
demonstrated in different stages of murine retinal development. GRID2
immunostaining was shown in murine and human retina. Whole-exome sequencing in
the proband did not provide arguments for other disease-causing mutations,
supporting the idea that the phenotype observed represents a single clinical
entity. CONCLUSION: We identified GRID2 as an underlying disease gene of early
onset autosomal recessive cerebellar ataxia with retinal dystrophy, expanding the
clinical spectrum of GRID2 deletion mutants. We demonstrated for the first time
GRID2 expression and localization in human and murine retina, providing evidence
for a novel functional role of GRID2 in the retina.
PMID- 25122144
TI - Exceptional aggressiveness of cerebral cavernous malformation disease associated
with PDCD10 mutations.
AB - PURPOSE: The phenotypic manifestations of cerebral cavernous malformation disease
caused by rare PDCD10 mutations have not been systematically examined, and a
mechanistic link to Rho kinase-mediated hyperpermeability, a potential
therapeutic target, has not been established. METHODS: We analyzed PDCD10 small
interfering RNA-treated endothelial cells for stress fibers, Rho kinase activity,
and permeability. Rho kinase activity was assessed in cerebral cavernous
malformation lesions. Brain permeability and cerebral cavernous malformation
lesion burden were quantified, and clinical manifestations were assessed in
prospectively enrolled subjects with PDCD10 mutations. RESULTS: We determined
that PDCD10 protein suppresses endothelial stress fibers, Rho kinase activity,
and permeability in vitro. Pdcd10 heterozygous mice have greater lesion burden
than other Ccm genotypes. We demonstrated robust Rho kinase activity in murine
and human cerebral cavernous malformation vasculature and increased brain
vascular permeability in humans with PDCD10 mutation. Clinical phenotype is
exceptionally aggressive compared with the more common KRIT1 and CCM2 familial
and sporadic cerebral cavernous malformation, with greater lesion burden and more
frequent hemorrhages earlier in life. We first report other phenotypic features,
including scoliosis, cognitive disability, and skin lesions, unrelated to lesion
burden or bleeding. CONCLUSION: These findings define a unique cerebral cavernous
malformation disease with exceptional aggressiveness, and they inform preclinical
therapeutic testing, clinical counseling, and the design of trials.Genet Med 17
3, 188-196.
PMID- 25122148
TI - Management of incus necrosis in revision stapedectomy using hydroxyapatite bone
cement.
AB - OBJECTIVE: Review audiological outcomes after revision stapedectomy using
hydroxyapatite cement. STUDY DESIGN: Retrospective case review. SETTING: Tertiary
neurotological referral center. PATIENTS: Thirty-seven cases of previously
treated otosclerosis where incus erosion was observed during revision
stapedectomy. INTERVENTION(S): Hydroxyapatite cement was used to rebuild the
eroded incus and stabilize the prosthesis during revision stapedectomy. MAIN
OUTCOME MEASURE(S): Pre- and postoperative bone conduction (BC) and air
conduction (AC) pure-tone averages (PTA) (0.5, 1, 2, 3 kHz) including high tone
BC (1, 2, 4 kHz), air-bone gap (ABG), and speech discrimination scores were
measured. Short-term (3 wk) and longer-term (average 12 mo) hearing outcomes were
measured. Data are reported according to the most recent guidelines of the AAO
HNS Committee on Hearing and Equilibrium. RESULTS: Among 37 ears undergoing
revision stapedectomy with hydroxyapatite cement, the AC PTA was 59.8 dB
preoperatively and 34.6 dB postoperatively (p < 0.0001) at latest follow-up. The
mean postoperative ABG was 8.8 dB (SD = 8.6, range -1.3-36.3 dB) while a mean
improvement of 2.1 dB (SD = 6.5, range -8.33-15.0 dB) of the high tone BC PTA was
observed. One revision case was noted during the follow-up period. CONCLUSION:
Hydroxyapatite cement is useful to reconstruct and stabilize the prosthesis in
revision stapedectomy when erosion of the long process is encountered. Short- and
longer-term hearing results are favorable when compared to previously reported
results of revision stapedectomy.
PMID- 25122149
TI - Bilateral hearing loss heralding sporadic Creutzfeldt-Jakob disease: a case
report and literature review.
AB - OBJECTIVE: To report a case of sporadic Creutzfeldt-Jakob disease (CJD) with
bilateral hearing loss at onset and literature review of the scarce cases of CJD
with similar audiologic manifestations at presentation. CASE REPORT: A 67-yr-old
man presented to the hospital for evaluation of rapid progression of behavioral
decline, unsteady gait, and bilateral hearing loss. Three months before
admission, he abruptly developed bilateral hypoacusis without associated tinnitus
or vertigo. Shortly after, his family noted an ataxic gait and behavioral
changes, for example, paranoid delusions. Initial workup, including a complete
autoimmune panel and heavy metals, infectious, toxicology, and paraneoplastic
panel (e.g., anti-Hu, anti-VGKC), was conducted. Electroencephalography revealed
diffuse generalized slowing without periodic complexes. The presence of
distortion product otoacoustic emissions bilaterally was consistent with normal
cochlear function, suggesting a retrocochlear origin for symptoms of hearing
loss. In the meantime, the patient developed startle myoclonus. The brain
magnetic resonance imaging demonstrated asymmetric cortical ribbon along with T2
FLAIR signal hyperintensities of bilateral basal ganglia. Later on, the protein
14-3-3 in the cerebrospinal fluid came back positive, which supported the
diagnosis of CJD. Only three cases of CJD with deafness at onset have been
published: one sporadic, associated with symptoms suggestive of polyneuropathy;
and the other two familial, with the E200K mutation. One presented with symptoms
of polyneuropathy and the other with typical features. CONCLUSION: This case
illustrates the phenotypic variability of presentation of CJD in a patient with
hearing loss as the initial manifestation. In patients with subacute bilateral
hypoacusis and signs of dementia, the differential diagnosis of CJD must be taken
into consideration.
PMID- 25122150
TI - Sex differences in response to tadalafil in pulmonary arterial hypertension.
AB - BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disease with
high rates of morbidity and mortality. Current therapies improve symptoms,
functional capacity, and, in select cases, survival. Little is known about
patient factors that may predict the likelihood of patient-important, clinically
relevant responses to therapy such as the 6-min walk distance (6MWD) and health
related quality of life (HRQoL). METHODS: Data from the randomized clinical trial
of tadalafil in PAH were used. Adjusted logistic regression models were created
to examine the relationship between baseline characteristics and odds of
achieving the minimal important difference (MID) in three parameters, defined as
either a > 33-m increase in 6MWD, a > 5-unit increase in physical component
summary score of the Medical Outcomes Study Short Form-36 (SF-36), or a > 5-unit
increase in mental component summary score of the SF-36. RESULTS: The study
included 405 subjects. Younger age, male sex, lower baseline 6MWD, and disease
etiology were associated with greater odds of achieving the MID for the 6-min
walk test. Active treatment, younger age, and male sex were associated with
greater odds of achieving the MID for the physical component summary score. Male
sex was associated with greater odds of achieving the MID for the mental
component summary score. CONCLUSIONS: Age, sex, baseline functional capacity, and
disease etiology are variably associated with the likelihood of achieving
clinically relevant responses in patient-important outcomes to PAH-specific
therapy such as 6MWD and HRQoL. The increased likelihood of response in men
compared with women is a novel finding and may reflect pathophysiologic
differences between sexes.
PMID- 25122152
TI - The Arabidopsis 14-3-3 protein RARE COLD INDUCIBLE 1A links low-temperature
response and ethylene biosynthesis to regulate freezing tolerance and cold
acclimation.
AB - In plants, the expression of 14-3-3 genes reacts to various adverse environmental
conditions, including cold, high salt, and drought. Although these results
suggest that 14-3-3 proteins have the potential to regulate plant responses to
abiotic stresses, their role in such responses remains poorly understood.
Previously, we showed that the RARE COLD INDUCIBLE 1A (RCI1A) gene encodes the 14
3-3 psi isoform. Here, we present genetic and molecular evidence implicating
RCI1A in the response to low temperature. Our results demonstrate that RCI1A
functions as a negative regulator of constitutive freezing tolerance and cold
acclimation in Arabidopsis thaliana by controlling cold-induced gene expression.
Interestingly, this control is partially performed through an ethylene (ET)
dependent pathway involving physical interaction with different ACC SYNTHASE
(ACS) isoforms and a decreased ACS stability. We show that, consequently, RCI1A
restrains ET biosynthesis, contributing to establish adequate levels of this
hormone in Arabidopsis under both standard and low-temperature conditions. We
further show that these levels are required to promote proper cold-induced gene
expression and freezing tolerance before and after cold acclimation. All these
data indicate that RCI1A connects the low-temperature response with ET
biosynthesis to modulate constitutive freezing tolerance and cold acclimation in
Arabidopsis.
PMID- 25122151
TI - The ABC transporter ABCG1 is required for suberin formation in potato tuber
periderm.
AB - The lipid biopolymer suberin plays a major role as a barrier both at plant
environment interfaces and in internal tissues, restricting water and nutrient
transport. In potato (Solanum tuberosum), tuber integrity is dependent on
suberized periderm. Using microarray analyses, we identified ABCG1, encoding an
ABC transporter, as a gene responsive to the pathogen-associated molecular
pattern Pep-13. Further analyses revealed that ABCG1 is expressed in roots and
tuber periderm, as well as in wounded leaves. Transgenic ABCG1-RNAi potato plants
with downregulated expression of ABCG1 display major alterations in both root and
tuber morphology, whereas the aerial part of the ABCG1-RNAi plants appear normal.
The tuber periderm and root exodermis show reduced suberin staining and
disorganized cell layers. Metabolite analyses revealed reduction of esterified
suberin components and hyperaccumulation of putative suberin precursors in the
tuber periderm of RNA interference plants, suggesting that ABCG1 is required for
the export of suberin components.
PMID- 25122155
TI - Water-soluble and cleavable quercetin-amino acid conjugates as safe modulators
for P-glycoprotein-based multidrug resistance.
AB - Quercetin-amino acid conjugates with alanine or glutamic acid moiety attached at
7-O and/or 3-O position of quercetin were prepared, and their multidrug
resistance (MDR)-modulatory effects were evaluated. A quercetin-glutamic acid
conjugate, 7-O-Glu-Q (3a), was as potent as verapamil in reversing MDR and
sensitized MDR MES-SA/Dx5 cells to various anticancer drugs with EC50 values of
0.8-0.9 MUM. Analysis on Rh-123 accumulation confirmed that 3a inhibits drug
efflux by Pgp, and Pgp ATPase assay showed that 3a interacts with the drug
binding site of Pgp to stimulate its ATPase activity. Physicochemical analysis of
3a revealed that solubility, stability, and cellular uptake of quercetin were
significantly improved by the glutamic acid promoiety, which eventually
dissociates from 3a to produce quercetin and quercetin metabolites in
intracellular milieu. Taken together, potent MDR-modulating activity along with
intracellular conversion into the natural flavonoid quercetin warrants
development of the quercetin-amino acid conjugates as safe MDR modulators.
PMID- 25122156
TI - Clinical audit: still an important tool for improving healthcare.
AB - The use of data to challenge and improve healthcare has a long and distinguished
history but has often failed to bring about expected improvements. It has never
become fully embedded in clinical practice, probably because data alone are
insufficient to drive change. There is now a greater appreciation that changing
and improving healthcare requires changing behaviours. Clinical audit remains one
of the important tools that can be used to facilitate such change.
PMID- 25122153
TI - Comparative transcriptome atlases reveal altered gene expression modules between
two Cleomaceae C3 and C4 plant species.
AB - C(4) photosynthesis outperforms the ancestral C(3) state in a wide range of
natural and agro-ecosystems by affording higher water-use and nitrogen-use
efficiencies. It therefore represents a prime target for engineering novel, high
yielding crops by introducing the trait into C(3) backgrounds. However, the
genetic architecture of C(4) photosynthesis remains largely unknown. To define
the divergence in gene expression modules between C(3) and C(4) photosynthesis
during leaf ontogeny, we generated comprehensive transcriptome atlases of two
Cleomaceae species, Gynandropsis gynandra (C(4)) and Tarenaya hassleriana (C(3)),
by RNA sequencing. Overall, the gene expression profiles appear remarkably
similar between the C(3) and C(4) species. We found that known C(4) genes were
recruited to photosynthesis from different expression domains in C(3), including
typical housekeeping gene expression patterns in various tissues as well as
individual heterotrophic tissues. Furthermore, we identified a structure-related
module recruited from the C(3) root. Comparison of gene expression patterns with
anatomy during leaf ontogeny provided insight into genetic features of Kranz
anatomy. Altered expression of developmental factors and cell cycle genes is
associated with a higher degree of endoreduplication in enlarged C(4) bundle
sheath cells. A delay in mesophyll differentiation apparent both in the leaf
anatomy and the transcriptome allows for extended vein formation in the C(4)
leaf.
PMID- 25122157
TI - Practical pharmacokinetics: what do you really need to know?
AB - Having some understanding of pharmacokinetics is important for all clinicians
when prescribing medications. Key elements to effective and safe prescribing
include making sure that we don't underdose a medication making it ineffective,
but also do not overprescribe a treatment known to cause toxic effects. In
paediatrics, there are significant physiological and developmental differences
that add to the challenges of safe prescribing. This article aims to provide the
clinician with some basic paediatric pharmacokinetic principles with clinical
examples to aid their prescribing skills.
PMID- 25122154
TI - Identification of a sphingolipid alpha-glucuronosyltransferase that is essential
for pollen function in Arabidopsis.
AB - Glycosyl inositol phosphorylceramide (GIPC) sphingolipids are a major class of
lipids in fungi, protozoans, and plants. GIPCs are abundant in the plasma
membrane in plants, comprising around a quarter of the total lipids in these
membranes. Plant GIPCs contain unique glycan decorations that include a conserved
glucuronic acid (GlcA) residue and various additional sugars; however, no
proteins responsible for glycosylating GIPCs have been identified to date. Here,
we show that the Arabidopsis thaliana protein INOSITOL PHOSPHORYLCERAMIDE
GLUCURONOSYLTRANSFERASE1 (IPUT1) transfers GlcA from UDP-GlcA to GIPCs. To
demonstrate IPUT1 activity, we introduced the IPUT1 gene together with genes for
a UDP-glucose dehydrogenase from Arabidopsis and a human UDP-GlcA transporter
into a yeast mutant deficient in the endogenous inositol phosphorylceramide (IPC)
mannosyltransferase. In this engineered yeast strain, IPUT1 transferred GlcA to
IPC. Overexpression or silencing of IPUT1 in Nicotiana benthamiana resulted in an
increase or a decrease, respectively, in IPC glucuronosyltransferase activity in
vitro. Plants in which IPUT1 was silenced accumulated IPC, the immediate
precursor, as well as ceramides and glucosylceramides. Plants overexpressing
IPUT1 showed an increased content of GIPCs. Mutations in IPUT1 are not
transmitted through pollen, indicating that these sphingolipids are essential in
plants.
PMID- 25122158
TI - Developing clinical guidelines: how much rigour is required?
AB - Clinical guidelines that are rigorously developed play a fundamental role in
improving healthcare and reducing unnecessary variations in practice. National
guidelines are increasingly used by healthcare professionals, patients and
commissioners; however, national bodies are unable to meet the demand for
guidance on all topics. There are fewer resources available for guidance produced
locally or by specialty groups, and it is necessary to achieve a balance between
pragmatism and rigour while conforming to the widely accepted norms of what
constitutes a good guideline. This paper introduces the key concepts around this
topic with suggestions for those interested in developing their own guideline. An
example of challenges encountered in generating high-quality clinical guidance is
given in box 1. Box 1 Challenges in guideline development Professor Johnson runs
a local developmental paediatrics service with eight other colleagues. All have
different ways of managing children with PAVING syndrome. This was difficult for
patients and staff and has led to disagreements on how certain patients should be
managed. As a result, Professor Johnson developed a Guideline Development Group
to look at the management of PAVING syndrome. The group identified 12 clinical
questions (including diagnosis, exclusion of comorbidities, treatment
modalities), searched the PubMed database and found some useful evidence that
they used to formulate key recommendations. For one question about behavioural
therapy, PubMed did not suggest any evidence so they informally arrived at a
consensus among themselves and wrote up their guideline. On the back of this
success, they applied for the guideline to be endorsed or supported by the Royal
College of Paediatrics and Child Health (RCPCH). To their frustration, it was
turned down on methodological grounds. Professor Johnson wrote to the RCPCH
saying that he was "pretty peeved that the PAVING syndrome guideline had been
rejected" for the College endorsement given all the work that had gone into
writing it and "would the College mind being a bit more explicit in their
guidance," to anyone who might consider doing this in the future?
PMID- 25122159
TI - PPAR ligands improve impaired metabolic pathways in fetal hearts of diabetic
rats.
AB - In maternal diabetes, the fetal heart can be structurally and functionally
affected. Maternal diets enriched in certain unsaturated fatty acids can activate
the nuclear receptors peroxisome proliferator-activated receptors (PPARs) and
regulate metabolic and anti-inflammatory pathways during development. Our aim was
to investigate whether PPARalpha expression, lipid metabolism, lipoperoxidation,
and nitric oxide (NO) production are altered in the fetal hearts of diabetic
rats, and to analyze the putative effects of in vivo PPAR activation on these
parameters. We found decreased PPARalpha expression in the hearts of male but not
female fetuses of diabetic rats when compared with controls. Fetal treatments
with the PPARalpha ligand leukotriene B4 upregulated the expression of PPARalpha
and target genes involved in fatty acid oxidation in the fetal hearts. Increased
concentrations of triglycerides, cholesterol, and phospholipids were found in the
hearts of fetuses of diabetic rats. Maternal treatments with diets supplemented
with 6% olive oil or 6% safflower oil, enriched in unsaturated fatty acids that
can activate PPARs, led to few changes in lipid concentrations, but up-regulated
PPARalpha expression in fetal hearts. NO production, which was increased in the
hearts of male and female fetuses in the diabetic group, and lipoperoxidation,
which was increased in the hearts of male fetuses in the diabetic group, was
reduced by the maternal treatments supplemented with safflower oil. In
conclusion, impaired PPARalpha expression, altered lipid metabolism, and
increased oxidative and nitridergic pathways were evidenced in hearts of fetuses
of diabetic rats and were regulated in a gender-dependent manner by treatments
enriched with PPAR ligands.
PMID- 25122160
TI - Structure of chitosan determines its interactions with mucin.
AB - Synthetic and natural mucoadhesive biomaterials in optimized galenical
formulations are potentially useful for the transmucosal delivery of active
ingredients to improve their localized and prolonged effects. Chitosans (CS) have
potent mucoadhesive characteristics, but the exact mechanisms underpinning such
interactions at the molecular level and the role of the specific structural
properties of CS remain elusive. In the present study we used a combination of
microviscosimetry, zeta potential analysis, isothermal titration calorimetry
(ITC) and fluorescence quenching to confirm that the soluble fraction of porcine
stomach mucin interacts with CS in water or 0.1 M NaCl (at c < c*; relative
viscosity, eta(rel), ~ 2.0 at pH 4.5 and 37 degrees C) via a heterotypic
stoichiometric process significantly influenced by the degree of CS acetylation
(DA). We propose that CS-mucin interactions are driven predominantly by
electrostatic binding, supported by other forces (e.g., hydrogen bonds and
hydrophobic association) and that the DA influences the overall conformation of
CS and thus the nature of the resulting complexes. Although the conditions used
in this model system are simpler than the typical in vivo environment, the
resulting knowledge will enable the rational design of CS-based nanostructured
materials for specific transmucosal drug delivery (e.g., for Helicobacter pylori
stomach therapy).
PMID- 25122161
TI - Transformation of the multidisciplinary diabetic foot clinic into a
multidisciplinary diabetic foot day unit: results from a service evaluation.
AB - The natural history of the diabetic foot is aggressive and complex. To counteract
this, we describe the transformation of a Multidisciplinary Diabetic Foot Clinic
into a Multidisciplinary Diabetic Foot Day Unit, which delivers an emergency open
access system for patients, with a "one-stop," same day service in which
investigations are performed, results reviewed and treatment implemented. It also
provides joint clinics with vascular, orthopaedic, and plastic surgeons and
specialized clinics for casting of complex neuropathic feet and for the
administration of intravenous or intramuscular antibiotics on the same day. The
aim was to document these increasingly wide-ranging facilities by undertaking a
retrospective evaluation over a 6-week period, with analysis of notes,
investigations, and an anonymous patient satisfaction survey. The clinic was
visited by 597 patients who attended in 1076 appointments, of which 112 (10.4%)
were emergency visits; these patients attended the clinic without a booked
appointment but via an open access policy, 93 of whom were known to the clinic,
but 19 were new self-referred patients to the service. Furthermore, 197 (18%)
were seen in a Joint Vascular Diabetic Foot Clinic and 98 (9%) were seen in a
Joint Orthopaedic Plastic Diabetic Foot Clinic, 570 (53%) were seen in an Active
Ulcer Clinic and 97 (9%) in a Total Contact Casting Clinic. Forty-five percent of
patients were prescribed antibiotics, including 188 (76%) as oral and 45(18%) as
intravenous antibiotics and 15(6%) as intramuscular injections. Of the 1076
appointments, 150 (14%) patients were in the foot clinic for more than 4 hours.
Sixty (10%) patients were reviewed 4 or more times over the 6-week period. Only
22 (2%) were admitted to hospital. Of the 125 survey responders, 98% were
satisfied with this service, which has evolved from a Diabetic Foot Clinic into a
Multidisciplinary Diabetic Foot Day Unit.
PMID- 25122162
TI - Diltiazem for the management of malignancy-associated perineal pain and tenesmus.
AB - BACKGROUND: Perineal pain is a frequent complaint of patients with advanced
cancer (colorectal, genitourinary, prostate), and often quite difficult to manage
with significant impact on quality of life. Calcium channel blockers (CCBs) are
potent inhibitors of intestinal smooth muscle contraction and have been shown to
impact tone and motility of the gastrointestinal tract. As such, they have been
used in various pain syndromes of the lower gastrointestinal tract, such as
chronic anal fissure, to promote healing and improve pain. Here we describe two
cases using oral diltiazem for malignancy-associated perineal pain and tenesmus.
DISCUSSION: The first case describes an elderly male with advanced urothelial
cancer post surgical resection and chemoradiation who suffered from rectal pain
described as "sitting on a football" despite nerve blocks and oral opioids. He
experienced dramatic improvement in pain scores and daily requirements of oral
analgesics after starting oral diltiazem. The second case describes a middle-aged
female with rectal cancer post surgical resection and chemoradiation who suffered
from quality-of-life-limiting rectal pain and pressure despite oral opioids. She
experienced dramatic improvement in the "pressure-type" pain after adding oral
diltiazem. CONCLUSION: Based on our experience with these two cases, we propose
oral diltiazem for use as an adjunct therapy for management of chronic malignancy
associated perineal pain, specifically with characteristics of pressure-type pain
and tenesmus.
PMID- 25122163
TI - Face mask sampling for the detection of Mycobacterium tuberculosis in expelled
aerosols.
AB - BACKGROUND: Although tuberculosis is transmitted by the airborne route, direct
information on the natural output of bacilli into air by source cases is very
limited. We sought to address this through sampling of expelled aerosols in face
masks that were subsequently analyzed for mycobacterial contamination. METHODS:
In series 1, 17 smear microscopy positive patients wore standard surgical face
masks once or twice for periods between 10 minutes and 5 hours; mycobacterial
contamination was detected using a bacteriophage assay. In series 2, 19 patients
with suspected tuberculosis were studied in Leicester UK and 10 patients with at
least one positive smear were studied in The Gambia. These subjects wore one
FFP30 mask modified to contain a gelatin filter for one hour; this was
subsequently analyzed by the Xpert MTB/RIF system. RESULTS: In series 1, the
bacteriophage assay detected live mycobacteria in 11/17 patients with wearing
times between 10 and 120 minutes. Variation was seen in mask positivity and the
level of contamination detected in multiple samples from the same patient. Two
patients had non-tuberculous mycobacterial infections. In series 2, 13/20
patients with pulmonary tuberculosis produced positive masks and 0/9 patients
with extrapulmonary or non-tuberculous diagnoses were mask positive. Overall, 65%
of patients with confirmed pulmonary mycobacterial infection gave positive masks
and this included 3/6 patients who received diagnostic bronchoalveolar lavages.
CONCLUSION: Mask sampling provides a simple means of assessing mycobacterial
output in non-sputum expectorant. The approach shows potential for application to
the study of airborne transmission and to diagnosis.
PMID- 25122167
TI - The floods in China: report by the medical director of the health organisation on
the work undertaken to co-ordinate the campaign against epidemics.
PMID- 25122164
TI - Qishenyiqi protects ligation-induced left ventricular remodeling by attenuating
inflammation and fibrosis via STAT3 and NF-kappaB signaling pathway.
AB - AIM: Qi-shen-yi-qi (QSYQ), a formula used for the routine treatment of heart
failure (HF) in China, has been demonstrated to improve cardiac function through
down-regulating the activation of the Renin-Angiotensin-Aldosterone System
(RAAS). However, the mechanisms governing its therapeutic effects are largely
unknown. The present study aims to demonstrate that QSYQ treatment can prevent
left ventricular remodeling in heart failure by attenuating oxidative stress and
inhabiting inflammation. METHODS: Sprague-Dawley (SD) rats were randomly divided
into 6 groups: sham group, model group (LAD coronary artery ligation), QSYQ group
with high dosage, middle dosage and low dosage (LAD ligation and treated with
QSYQ), and captopril group (LAD ligation and treated with captopril as the
positive drug). Indicators of fibrosis (Masson, MMPs, and collagens) and
inflammation factors were detected 28 days after surgery. RESULTS: Results of
hemodynamic alterations (dp/dt value) in the model group as well as other
ventricular remodeling (VR) markers, such as MMP-2, MMP-9, collagen I and III
elevated compared with sham group. VR was accompanied by activation of RAAS
(angiotensin II and NADPHoxidase). Levels of pro-inflammatory cytokines (TNF
alpha, IL-6) in myocardial tissue were also up-regulated. Treatment of QSYQ
improved cardiac remodeling through counter-acting the aforementioned events. The
improvement of QSYQ was accompanied with a restoration of angiotensin II
NADPHoxidase-ROS-MMPs pathways. In addition, "therapeutic" QSYQ administration
can reduce both TNF-alpha-NF-B and IL-6-STAT3 pathways, respectively, which
further proves the beneficial effects of QSYQ. CONCLUSIONS: Our study
demonstrated that QSYQ protected LAD ligation-induced left VR via attenuating
AngII -NADPH oxidase pathway and inhabiting inflammation. These findings provide
evidence as to the cardiac protective efficacy of QSYQ to HF and explain the
beneficial effects of QSYQ in the clinical application for HF.
PMID- 25122165
TI - ATO/ATRA/anthracycline-chemotherapy sequential consolidation achieves long-term
efficacy in primary acute promyelocytic leukemia.
AB - The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3,
ATO) has been effective in obtaining high clinical complete remission (CR) rates
in acute promyelocytic leukemia (APL), but the long-term efficacy and safety
among newly diagnosed APL patients are unclear. In this retrospective study,
total 45 newly diagnosed APL patients received ATRA/chemotherapy combination
regimen to induce remission. Among them, 43 patients (95.6%) achieved complete
remission (CR) after induction therapy, followed by ATO/ATRA/anthracycline-based
chemotherapy sequential consolidation treatment with a median follow-up of 55
months. In these patients, the estimated overall survival (OS) and the relapse
free survival (RFS) were 94.4% +/- 3.9% and 94.6 +/- 3.7%, respectively. The
toxicity profile was mild and reversible. No secondary carcinoma was observed.
These results demonstrated the high efficacy and minimal toxicity of
ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment for
newly diagnosed APL in long-term follow-up, suggesting a potential frontline
therapy for APL.
PMID- 25122170
TI - Genetics and health communication: a primer.
AB - The progress of genetic knowledge has been swift and steadfast. As we move
forward in the genomic era, post Human Genome Project, and continue to explore
how one's genes interact with one's environment, it becomes increasingly
important for all audiences to have a firm grasp of the vocabulary used in this
health context. This primer is intended to be used as a reference and to
introduce and/or make more clear concepts related to genetics to increase
understanding.
PMID- 25122166
TI - In vitro and in vivo studies for assessing the immune response and protection
inducing ability conferred by Fasciola hepatica-derived synthetic peptides
containing B- and T-cell epitopes.
AB - Fasciolosis is considered the most widespread trematode disease affecting grazing
animals around the world; it is currently recognised by the World Health
Organisation as an emergent human pathogen. Triclabendazole is still the most
effective drug against this disease; however, resistant strains have appeared and
developing an effective vaccine against this disease has increasingly become a
priority. Several bioinformatics tools were here used for predicting B- and T
cell epitopes according to the available data for Fasciola hepatica protein amino
acid sequences. BALB/c mice were immunised with the synthetic peptides by using
the ADAD vaccination system and several immune response parameters were measured
(antibody titres, cytokine levels, T-cell populations) to evaluate their ability
to elicit an immune response. Based on the immunogenicity results so obtained,
seven peptides were selected to assess their protection-inducing ability against
experimental infection with F. hepatica metacercariae. Twenty-four B- or T
epitope-containing peptides were predicted and chemically synthesised.
Immunisation of mice with peptides so-called B1, B2, B5, B6, T14, T15 and T16
induced high levels of total IgG, IgG1 and IgG2a (p<0.05) and a mixed
Th1/Th2/Th17/Treg immune response, according to IFN-gamma, IL-4, IL-17 and IL-10
levels, accompanied by increased CD62L+ T-cell populations. A high level of
protection was obtained in mice vaccinated with peptides B2, B5, B6 and T15
formulated in the ADAD vaccination system with the AA0029 immunomodulator. The
bioinformatics approach used in the present study led to the identification of
seven peptides as vaccine candidates against the infection caused by Fasciola
hepatica (a liver-fluke trematode). However, vaccine efficacy must be evaluated
in other host species, including those having veterinary importance.
PMID- 25122171
TI - Post-processing in cardiovascular computed tomography: performance of a client
server solution versus a stand-alone solution.
AB - PURPOSE: To compare the performance of server-based (CSS) versus stand-alone post
processing software (ES) for the evaluation of cardiovascular CT examinations
(cvCT) and to determine the crucial steps. MATERIALS AND METHODS: Data of 40
patients (20 patients for coronary artery evaluation and 20 patients prior to
transcatheter aortic valve implantation [TAVI]) were evaluated by 5 radiologists
with CSS and ES. Data acquisition was performed using a dual-source 128-row CT
unit (SOMATOM Definition Flash, Siemens, Erlangen, Germany) and a 64-row CT unit
(Brilliance 64, Philips, Hamburg, Germany). The following workflow was evaluated:
Data loading, aorta and coronary segmentation, curved multiplanar reconstruction
(cMPR) and 3 D volume rendering technique (3D-VRT), measuring of coronary artery
stenosis and planimetry of the aortic annulus. The time requirement and
subjective quality for the workflow were evaluated. RESULTS: The coronary
arteries as well as the TAVI data could be evaluated significantly faster with
CSS (5.5 +/- 2.9 min and 8.2 +/- 4.0 min, respectively) than with ES (13.9
+/- 5.2 min and 15.2 +/- 10.9 min, respectively, p <= 0.01). Segmentation
of the aorta (CSS: 1.9 +/- 2.0 min, ES: 3.7 +/- 3.3 min), generating cMPR of
coronaries (CSS: 0.5 +/- 0.2 min, ES: 5.1 +/- 2.6 min), aorta and iliac
vessels (CSS: 0.5 +/- 0.4 min and 0.4 +/- 0.4 min, respectively, ES: 1.6
+/- 0.7 min and 2.8 +/- 3 min, respectively) could be performed
significantly faster with CSS than with ES with higher quality of cMPR, measuring
of coronary stenosis and 3D-VRT (p < 0.05). CONCLUSION: Evaluation of cvCT can be
accomplished significantly faster and better with CSS than with ES. The
segmentation remains the most time-consuming workflow step, so optimization of
segmentation algorithms could improve performance even further.
PMID- 25122172
TI - The role of volume perfusion CT in the diagnosis of pathologies of the pancreas.
AB - The review discusses the potential role of volume perfusion CT (VPCT) in the
diagnosis and follow-up of different pathologies of the pancreas. VPCT enables a
differentiation of different pancreatic tumors like adenocarcinoma or
neuroendocrine tumors based on functional parameters like blood flow, blood
volume and permeability. Furthermore, the article discusses the potential
indications for VPCT imaging of inflammatory diseases of the pancreas such as
acute or chronic pancreatitis and autoimmune pancreatitis.
PMID- 25122173
TI - Radiological evaluation of the therapeutic response of malignant diseases: status
quo, innovative developments and requirements for radiology.
AB - In consequence of the rapid development of newer targeted and personalized tumor
therapies, radiology as an essential component of the treatment concept of
numerous malignant diseases needs to improve in order to adequately capture and
evaluate the effects, but also the side effects of these novel therapeutic
agents. The early recognition of therapy response or failure is crucial for the
optimal planning of the further treatment and can therefore have direct impact on
the chances of recovery and the survival time of oncological patients. In
previous years, the goal of medical imaging was to just qualitatively assess the
increase or reduction in the size of tumors and their metastases, which was often
achieved by a simple subjective estimation of the tumor findings by the
diagnosing radiologist. Nowadays, radiology is faced with the challenge of
evaluating changes during therapy quantitatively and of visualizing therapeutic
effects that are more discrete (e. g. necrosis, altered tumor perfusion). The
importance of an adequate assessment of therapy response is further underlined by
the fact that in these days, a good portion of oncological patients are enrolled
in clinical trials, in which the quantitative radiological evaluation of
malignant disorders is an important surrogate parameter. On the basis of this
development, the demands for radiology to provide more sophisticated assessments
of therapy response and documentation of imaging findings have been constantly
growing. The following article provides an overview of the established and still
widely spread but in particular also the latest imaging modalities and evaluation
criteria with regard to oncological diseases as well as of the increasing demands
on radiology that result from these developments. Beyond that, future
advancements in tumor imaging are taken into account and the new challenges these
developments will bring are discussed. KEY POINTS: * In the era of personalized
medicine, evaluation criteria that are individually adapted to the respective
patient are required.* Radiology needs to substantially contribute to oncological
treatment concepts and the evaluation of therapeutic response.
PMID- 25122175
TI - [A rare complication of pulmonary tuberculosis - Rasmussen aneurysm - radiologic
diagnosis and therapy].
PMID- 25122174
TI - S3 guideline for chronic pancreatitis - diagnosis, classification and therapy for
the radiologist.
AB - Chronic pancreatitis shows an increasing prevalence and incidence mainly in the
Western Hemisphere. Early diagnosis and therapy are frequently delayed because of
non-specific symptoms as well as non-specific blood values. The German Society of
Digestive and Metabolic Diseases (DGVS) organized the preparation and publication
of an interdisciplinary S3 level guideline with the support of the German
Radiological Society (DRG) as 1 of 11 contributing societies. In this article we
present and discuss the main topics of the guideline regarding the diagnosis,
differential diagnosis and therapy of complications of this complex chronic
disease with a focus on clinical and scientific radiologists. KEY POINTS: *
Ultarsound represents the perfect first line imaging modality * For further
diagnostic werk up MRI with MRCP are recommended for the differential diagnosis
of pancreatic cancer * For clinical studies the modified (CT, MRI) Cambridge
classification is recommended.
PMID- 25122176
TI - [A rare complication: acute ischemic stomach necrosis within the scope of non
occlusive mesenteric ischemia (NOMI)].
PMID- 25122177
TI - [Contrast medium going astray].
PMID- 25122178
TI - [Chronic adhesive small intestine volvulus in adulthood, a rare disease picture].
PMID- 25122179
TI - [Osteolytic behavior of a growing tumor of the calvarium: rare differential
intraosseous meningioma diagnosis].
PMID- 25122180
TI - A systematic review of scope and quality of health economic evaluation studies in
Vietnam.
AB - INTRODUCTION: The application of health economic evaluation (HEE) evidence can
play an important role in strategic planning and policy making. This study aimed
to assess the scope and quality of existing research, with the goal of
elucidating implications for improving the use of HEE evidence in Vietnam.
METHODS: A comprehensive search strategy was developed to search medical online
databases (Medline, Google Scholar, and Vietnam Medical Databases) to select all
types of HEE studies except cost-only analyses. Two researchers assessed the
quality of selected studies using the Quality of Health Economic Studies (QHES)
instrument. RESULTS: We selected 26 studies, including 6 published in Vietnam.
The majority of these studies focused on infectious diseases (14 studies), with
HIV being the most common topic (5 studies). Most papers were cost-effectiveness
studies that measured health outcomes using DALY units. Using QHES, we found that
the overall quality of HEE studies published internationally was much higher
(mean score 88.7+13.3) than that of those published in Vietnam (mean score
67.3+22.9). Lack of costing perspectives, reliable data sources and sensitivity
analysis were the main shortcomings of the reviewed studies. CONCLUSION: This
review indicates that HEE studies published in Vietnam are limited in scope and
number, as well as by several important technical errors or omissions. It is
necessary to formalize the process of health economic research in Vietnam and to
institutionalize the links between researchers and policy-makers. Additionally,
the quality of HEE should be enhanced through education about research
techniques, and the implementation of standard HEE guidelines.
PMID- 25122181
TI - Multivitamin and protein supplement use is associated with positive mood states
and health behaviors in US Military and Coast Guard personnel.
AB - Approximately 60% of Armed Forces personnel regularly consume dietary supplements
(DSs). We investigated the association of mood and health behaviors with multiple
classes of DSs in military and Coast Guard personnel (N = 5536). Participants
completed a survey of DS use and the Quick Mood Scale to assess mood domains of
wakeful-drowsiness, relaxed-anxious, cheerful-depressed, friendly-aggression,
clearheaded-confused, and well coordinated-clumsy. Supplements were categorized
as multivitamin/minerals (MVM), individual vitamin/minerals, protein/amino acid
supplements (PS), combination products (C), herbals (H), purported steroid
analogs, (S) and other (O). One-way analyses of covariance assessed associations
of DSs and perceived health behavior with mood controlling for age. Logistic
regression determined associations between DS use and health behavior. Users of
MVM and PS reported feeling significantly (P < 0.05) more awake, relaxed,
cheerful, clearheaded, and coordinated. Participants using PS and S reported
feeling less friendly (more aggressive, P < 0.02). Users of MVM and PS were more
likely to report their general health, eating habits, and fitness level as
excellent/good (P < 0.05). Participants reporting health behaviors as
excellent/good were more (P < 0.01) awake, relaxed, cheerful, friendly,
clearheaded, and coordinated. As no known biological mechanisms can explain such
diverse effects of MVM and PS use on multiple mood states, health, eating habits,
and fitness, we hypothesize these associations are not causal, and DS intake does
not alter these parameters per se. Preexisting differences in mood and other
health-related behaviors and outcomes between users versus nonusers of DSs could
be a confounding factor in studies of DSs.
PMID- 25122182
TI - MicroRNA-30e* suppresses dengue virus replication by promoting NF-kappaB
dependent IFN production.
AB - MicroRNAs have been shown to contribute to a repertoire of host-pathogen
interactions during viral infection. Our previous study demonstrated that
microRNA-30e* (miR-30e*) directly targeted the IkappaBalpha 3'-UTR and disrupted
the NF-kappaB/IkappaBalpha negative feedback loop, leading to hyperactivation of
NF-kappaB. This current study investigated the possible role of miR-30e* in the
regulation of innate immunity associated with dengue virus (DENV) infection. We
found that DENV infection could induce miR-30e* expression in DENV-permissive
cells, and such an overexpression of miR-30e* upregulated IFN-beta and the
downstream IFN-stimulated genes (ISGs) such as OAS1, MxA and IFITM1, and
suppressed DENV replication. Furthermore, suppression of IkappaBalpha mediates
the enhancing effect of miR-30e* on IFN-beta-induced antiviral response.
Collectively, our findings suggest a modulatory role of miR-30e* in DENV induced
IFN-beta signaling via the NF-kappaB-dependent pathway. Further investigation is
needed to evaluate whether miR-30e* has an anti-DENV effect in vivo.
PMID- 25122184
TI - Rape in war: how a US law prevents aid for safe abortions.
PMID- 25122183
TI - Mannosylation of virus-like particles enhances internalization by antigen
presenting cells.
AB - Internalization of peptides by antigen presenting cells is crucial for the
initiation of the adaptive immune response. Mannosylation has been demonstrated
to enhance antigen uptake through mannose receptors, leading to improved immune
responses. In this study we test the effect of surface mannosylation of protein
based virus-like particles (VLP) derived from Rabbit hemorrhagic disease virus
(RHDV) on uptake by murine and human antigen presenting cells. A monomannoside
and a novel dimannoside were synthesized and successfully conjugated to RHDV VLP
capsid protein, providing approximately 270 mannose groups on the surface of each
virus particle. VLP conjugated to the mannoside or dimannoside exhibited
significantly enhanced binding and internalization by murine dendritic cells,
macrophages and B cells as well as human dendritic cells and macrophages. This
uptake was inhibited by the inclusion of mannan as a specific inhibitor of
mannose specific uptake, demonstrating that mannosylation of VLP targets mannose
receptor-based uptake. Consistent with mannose receptor-based uptake, partial
retargeting of the intracellular processing of RHDV VLP was observed, confirming
that mannosylation of VLP provides both enhanced uptake and modified processing
of associated antigens.
PMID- 25122187
TI - All of the above: When multiple correct response options enhance the testing
effect.
AB - Previous research has shown that multiple choice tests often improve memory
retention. However, the presence of incorrect lures often attenuates this memory
benefit. The current research examined the effects of "all of the above" (AOTA)
options. When such options are correct, no incorrect lures are present. In the
first three experiments, a correct AOTA option on an initial test led to a larger
memory benefit than no test and standard multiple choice test conditions. The
benefits of a correct AOTA option occurred even without feedback on the initial
test; for both 5-minute and 48-hour retention delays; and for both cued recall
and multiple choice final test formats. In the final experiment, an AOTA question
led to better memory retention than did a control condition that had identical
timing and exposure to response options. However, the benefits relative to this
control condition were similar regardless of the type of multiple choice test
(AOTA or not). Results suggest that retrieval contributes to multiple choice
testing effects. However, the extra testing effect from a correct AOTA option,
rather than being due to more retrieval, might be due simply to more exposure to
correct information.
PMID- 25122185
TI - A nationwide study of SLE in Japanese identified subgroups of patients with clear
signs patterns and associations between signs and age or sex.
AB - We performed a nationwide study to determine the distributions of the signs and
clinical markers of systemic lupus erythematosus (SLE) and identify any patterns
in their distributions to allow patient subclassification. We obtained 256,999
patient-year records describing the disease status of SLE patients from 2003 to
2010. Of these, 14,779 involved patients diagnosed within the last year, and
242,220 involved patients being followed up. Along with basic descriptive
statistics, we analyzed the effects of sex, age and disease duration on the
frequencies of signs in the first year and follow-up years. The patients and
major signs were clustered using the Ward method. The female patients were
younger at onset. Renal involvement and discoid eczema were more frequent in
males, whereas arthritis, photosensitivity and cytopenia were less. Autoantibody
production and malar rash were positively associated with young age, and
serositis and arthritis were negatively associated. Photosensitivity was
positively associated with a long disease duration, and autoantibody production,
serositis and cytopenia were negatively associated. The SLE patients were
clustered into subgroups, as were the major signs. We identified differences in
SLE clinical features according to sex, age and disease duration. Subgroups of
SLE patients and the major signs of SLE exist.
PMID- 25122188
TI - Ovarian stimulation using human chorionic gonadotrophin impairs blastocyst
implantation and decidualization by altering ovarian hormone levels and
downstream signaling in mice.
AB - Ovarian stimulation induced by follicle-stimulating hormone and human chorionic
gonadotrophin (hCG) is commonly used in assisted reproductive technology to
increase embryo production. However, recent clinical and animal studies have
shown that ovarian stimulation disrupts endometrial function and embryo
development and adversely affects pregnancy outcomes. How ovarian stimulation
impairs pregnancy establishment and the precise mechanisms by which this
stimulation reduces the chances of conception remain unclear. In this study, we
first demonstrated that ovarian stimulation using hCG alone impairs implantation,
decidualization and fetal development of mice by generating abnormal ovarian
hormone levels. We also showed that ovarian hormone levels were altered because
of changes in the levels of the enzymes involved in their synthesis in the
follicles and corpora lutea. Furthermore, we determined that anomalous ovarian
hormone secretion induced by ovarian stimulation alters the spatiotemporal
expression of progesterone receptors and their downstream genes, especially in
the uterine epithelium. Epithelial estrogenic signaling and cell proliferation
were promoted on the day of implantation in stimulated mice and these changes led
to the failure of uterine transition from the prereceptive to the receptive
state. Collectively, our findings indicate that ovarian stimulation using hCG
induces an imbalance in steroid hormone secretion, which causes a failure of the
development of uterine receptivity and subsequent implantation and
decidualization by altering the expression of steroid receptors and their
downstream signaling associated with embryo implantation.
PMID- 25122186
TI - Cardiac structure and function and prognosis in heart failure with preserved
ejection fraction: findings from the echocardiographic study of the Treatment of
Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT)
Trial.
AB - BACKGROUND: Abnormalities in cardiac structure and function in heart failure with
preserved ejection fraction may help identify patients at particularly high risk
for cardiovascular morbidity and mortality. METHODS AND RESULTS: Cardiac
structure and function were assessed by echocardiography in a blinded core
laboratory at baseline in 935 patients with heart failure with preserved ejection
fraction (left ventricular ejection fraction >=45%) enrolled in the Treatment of
Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT)
trial and related to the primary composite outcome of cardiovascular death, heart
failure hospitalization, or aborted cardiac arrest, and its components. At a
median follow-up of 2.9 years, 244 patients experienced the primary outcome. Left
ventricular hypertrophy (adjusted hazard ratio, 1.52; 95% confidence interval,
1.16-2.00), elevated left ventricular filling pressure (E/E'; adjusted hazard
ratio 1.05 per 1 integer increase; 95% confidence interval, 1.02-1.07), and
higher pulmonary artery pressure assessed by the tricuspid regurgitation velocity
(hazard ratio, 1.23 per 0.5 m/s increase; 95% confidence interval, 1.02-1.49)
were associated with the composite outcome and heart failure hospitalization
alone after adjusting for clinical and laboratory variables. The risk of adverse
outcome associated with left ventricular hypertrophy was additive to the risk
associated with elevated E/E'. CONCLUSIONS: Among heart failure with preserved
ejection fraction patients enrolled in TOPCAT, left ventricular hypertrophy,
higher left ventricular filling pressure, and higher pulmonary artery pressure
were predictive of heart failure hospitalization, cardiovascular death, or
aborted cardiac arrest independent of clinical and laboratory predictors. These
features, both alone and in combination, identify heart failure with preserved
ejection fraction patients at particularly high risk for cardiovascular morbidity
and mortality. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov.
Unique identifier: NCT00094302.
PMID- 25122190
TI - Dual-channel-mediated spin coupling for one-electron-oxidized cobalt(II)-saddled
porphyrin.
AB - Saddle-shaped Co(II)[OET(p-R)PP] (R = CF3, H, CH3) can be readily oxidized with
Cl2, Br2, and I2 to the corresponding one-electron-oxidation product Co[OET(p
R)PP]X (X = Cl, Br, I) with the clear character of a ring cation radical. With
the series of (1)H and (13)C NMR spectra of these related complexes, both the
axial ligand and peripheral substituent of the ring macrocycle are proven to act
as a dual channel to tune spin coupling between low-spin Co(II) and a porphyrin
pi-cation radical. Density functional theory calculations have shown that the
antiferromagnetic coupling between spins residing in d(z)(2) and a(2u) are
expected to exist as the ground state. The paramagnetic properties are attributed
to an a(1u)-type ferromagnetic excited triplet state.
PMID- 25122189
TI - Treatment selections using risk-benefit profiles based on data from comparative
randomized clinical trials with multiple endpoints.
AB - In a typical randomized clinical study to compare a new treatment with a control,
oftentimes each study subject may experience any of several distinct outcomes
during the study period, which collectively define the "risk-benefit" profile. To
assess the effect of treatment, it is desirable to utilize the entirety of such
outcome information. The times to these events, however, may not be observed
completely due to, for example, competing risks or administrative censoring. The
standard analyses based on the time to the first event, or individual component
analyses with respect to each event time, are not ideal. In this paper, we
classify each patient's risk-benefit profile, by considering all event times
during follow-up, into several clinically meaningful ordinal categories. We first
show how to make inferences for the treatment difference in a two-sample setting
where categorical data are incomplete due to censoring. We then present a
systematic procedure to identify patients who would benefit from a specific
treatment using baseline covariate information. To obtain a valid and efficient
system for personalized medicine, we utilize a cross-validation method for model
building and evaluation and then make inferences using the final selected
prediction procedure with an independent data set. The proposal is illustrated
with the data from a clinical trial to evaluate a beta-blocker for treating
chronic heart failure patients.
PMID- 25122192
TI - Inner and outer portions of colonic circular muscle: ultrastructural and
immunohistochemical changes in rat chronically treated with otilonium bromide.
AB - Rat colonic circular muscle, main target of otilonium bromide (OB) spasmolytic
activity, is subdivided in an inner and outer portion. Since the inner one is
particularly rich in organelles involved in calcium availability (caveolae,
smooth endoplasmic reticulum, mitochondria), the expression of specific markers
(Caveolin-1, eNOS, calreticulin, calsequestrin) in comparison with the outer
portion was investigated. The possible changes of these organelles and related
markers, and of muscarinic receptors (Mr2) were then studied after OB chronic
exposition. Rats were treated with 2-20 mg/kg/OB for 10 or 30 days. Proximal
colon was processed by electron microscopy, immunohistochemistry, and western
blot. In colon strips the stimulated contractility response to muscarinic agonist
was investigated. The inner portion showed a higher expression of Caveolin-1 and
Mr2, but not of eNOS, calreticulin and calsequestrin, compared to the outer
portion. Chronic OB treatment caused similar ultrastructural and
immunohistochemical changes in both portions. Organelles and some related markers
were increased at 10 days; Mr2 expression and muscle contractility induced by
methacholine was increased at 30 days. The present findings: 1) provide new
information on the immunohistochemical properties of the inner portion of the
circular layer that are in favour of a role it might play in colonic motility
distinct from that of the outer portion; 2) demonstrate that chronically
administered OB interferes with cell structures and molecules responsible for
calcium handling and storage, and modifies cholinergic transmission. In
conclusion, chronic OB administration in the colonic circular muscle layer
directly interacts with the organelles and molecules calcium-related and with the
Mr2.
PMID- 25122194
TI - Regulating new psychoactive drugs: innovation leading to compromise.
PMID- 25122195
TI - Graphene in the aquatic environment: adsorption, dispersion, toxicity and
transformation.
AB - Graphene-family nanomaterials (GFNs) including pristine graphene, reduced
graphene oxide (rGO) and graphene oxide (GO) offer great application potential,
leading to the possibility of their release into aquatic environments. Upon
exposure, graphene/rGO and GO exhibit different adsorption properties toward
environmental adsorbates, thus the molecular interactions at the GFN-water
interface are discussed. After solute adsorption, the dispersion/aggregation
behaviors of GFNs can be altered by solution chemistry, as well as by the
presence of colloidal particles and biocolloids. GO has different dispersion
performance from pristine graphene and rGO, which is further demonstrated from
surface properties. Upon exposure in aquatic environments, GFNs have adverse
impacts on aquatic organisms (e.g., bacteria, algae, plants, invertebrates, and
fish). The mechanisms of GFNs toxicity at the cellular level are reviewed and the
remaining unclear points on toxic mechanisms such as membrane damage are
presented. Moreover, we highlight the transformation routes of GO to rGO. The
degradation of GFNs upon exposure to UV irradiation and/or biota is also
reviewed. In view of the unanswered questions, future research should include
comprehensive characterization of GFNs, new approaches for explaining GFNs
aggregation, environmental behaviors of metastable GO, and the relationship
between dispersion of GFNs and the related adsorption properties.
PMID- 25122199
TI - Prevalence of chronic skin and musculoskeletal conditions, United States-1969.
AB - During 1969 the prevalence of chronic skin ,and musculoskeletal diseases among
members of the civilian noninstitutionalized population was measured in the
Health Interview Survey. Prevalence estimates and measures of impact of these
conditions on the population covered by the Survey are presented in this report.
This is the first report on the prevalence of chronic skin and musculoskeletal
conditions based on data collected in health interviews to be published in the
series, Vital and Health Statistics, and is one in a series of reports on
specific condition groups (Series 10, Nos. 83,84, and 94). Methodological studies
have shown that chronic conditions are generally underreported in interview
surveys. Respondents in health interviews can report only those conditions of
which they are aware and which they are willing to report to the interviewer.
Reporting is better for those conditions which have made an impact on the
affected individual and his family. Conditions that are severe, costly, or
require treatment tend to be better reported than conditions having lesser
impact. For instance, a condition which has caused hospitalization, limitation of
activity, visits to the doctor, or days in bed is more likely to be reported in
the interview than a condition which has little or no impact on the person.
PMID- 25122196
TI - Epithelial and stromal microRNA signatures of columnar cell hyperplasia linking
Let-7c to precancerous and cancerous breast cancer cell proliferation.
AB - Columnar cell hyperplasia (CCH) is the earliest histologically identifiable
breast lesion linked to cancer progression and is characterized by increased
proliferation, decreased apoptosis and elevated oestrogen receptor alpha
(ERalpha) expression. The mechanisms underlying the initiation of these lesions
have not been clarified but might involve early and fundamental changes in cancer
progression. MiRNAs are key regulators of several biological processes, acting by
influencing the post-transcriptional regulation of numerous targets, thus making
miRNAs potential candidates in cancer initiation. Here we have defined novel
epithelial as well as stromal miRNA signatures from columnar cell hyperplasia
lesions compared to normal terminal duct lobular units by using microdissection
and miRNA microarrays. Let-7c were among the identified downregulated epithelial
miRNAs and its functions were delineated in unique CCH derived cells and breast
cancer cell line MCF-7 suggesting anti-proliferative traits potentially due to
effects on Myb and ERalpha. MiR-132 was upregulated in the stroma surrounding CCH
compared to stoma surrounding normal terminal duct lobular units (TDLUs), and
overexpression of miR-132 in immortalized fibroblasts and in fibroblasts co
cultured with epithelial CCH cells caused substantial expression changes of genes
involved in metabolism, DNA damage and cell motility. The miRNA signatures
identified in CCH indicate early changes in the epithelial and stromal
compartment of CCH and could represent early key alterations in breast cancer
progression that potentially could be targeted in novel prevention or treatment
schedules.
PMID- 25122200
TI - Adult stroke risk after growth hormone treatment in childhood: first do no harm.
PMID- 25122193
TI - Global genetic variations predict brain response to faces.
AB - Face expressions are a rich source of social signals. Here we estimated the
proportion of phenotypic variance in the brain response to facial expressions
explained by common genetic variance captured by ~ 500,000 single nucleotide
polymorphisms. Using genomic-relationship-matrix restricted maximum likelihood
(GREML), we related this global genetic variance to that in the brain response to
facial expressions, as assessed with functional magnetic resonance imaging (fMRI)
in a community-based sample of adolescents (n = 1,620). Brain response to facial
expressions was measured in 25 regions constituting a face network, as defined
previously. In 9 out of these 25 regions, common genetic variance explained a
significant proportion of phenotypic variance (40-50%) in their response to
ambiguous facial expressions; this was not the case for angry facial expressions.
Across the network, the strength of the genotype-phenotype relationship varied as
a function of the inter-individual variability in the number of functional
connections possessed by a given region (R(2) = 0.38, p<0.001). Furthermore, this
variability showed an inverted U relationship with both the number of observed
connections (R2 = 0.48, p<0.001) and the magnitude of brain response (R(2) =
0.32, p<0.001). Thus, a significant proportion of the brain response to facial
expressions is predicted by common genetic variance in a subset of regions
constituting the face network. These regions show the highest inter-individual
variability in the number of connections with other network nodes, suggesting
that the genetic model captures variations across the adolescent brains in co
opting these regions into the face network.
PMID- 25122197
TI - Increased generation of HIV-1 gp120-reactive CD8+ T cells by a DNA vaccine
construct encoding the chemokine CCL3.
AB - DNA vaccines based on subunits from pathogens have several advantages over other
vaccine strategies. DNA vaccines can easily be modified, they show good safety
profiles, are stable and inexpensive to produce, and the immune response can be
focused to the antigen of interest. However, the immunogenicity of DNA vaccines
which is generally quite low needs to be improved. Electroporation and co
delivery of genetically encoded immune adjuvants are two strategies aiming at
increasing the efficacy of DNA vaccines. Here, we have examined whether targeting
to antigen-presenting cells (APC) could increase the immune response to surface
envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV
1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody,
which enables covalent fusion of gp120 to molecules that can target APC. Two
molecules were tested for their efficiency as targeting units: the antibody
derived single chain Fragment variable (scFv) specific for the major
histocompatibility complex (MHC) class II I-E molecules, and the CC chemokine
ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or
without electroporation. Targeting of gp120 to MHC class II molecules induced
antibodies that neutralized HIV-1 and that persisted for more than a year after
one single immunization with electroporation. Targeting by CCL3 significantly
increased the number of HIV-1 gp120-reactive CD8+ T cells compared to non
targeted vaccines and gp120 delivered alone in the absence of electroporation.
The data suggest that chemokines are promising molecular adjuvants because small
amounts can attract immune cells and promote immune responses without advanced
equipment such as electroporation.
PMID- 25122201
TI - Bulbar muscle MRI changes in patients with SMA with reduced mouth opening and
dysphagia.
AB - OBJECTIVE: We performed a study in patients with proximal spinal muscular atrophy
(SMA) to determine the prevalence of reduced maximal mouth opening (MMO) and its
association with dysphagia as a reflection of bulbar dysfunction and visualized
the underlying mechanisms using MRI. METHODS: We performed a cross-sectional
study of MMO in 145 patients with SMA types 1-4 and 119 healthy controls and used
MRI in 12 patients to visualize mandibular condylar shape and sliding and the
anatomy of muscle groups relevant for mouth opening and closing. We analyzed
associations of reduced MMO with SMA severity and complaints of dysphagia.
RESULTS: Reduced MMO was defined as an interincisal distance <= 35 mm and was
found in none of the healthy controls and in 100%, 79%, 50%, and 7% of patients
with SMA types 1, 2, 3a, and 3b/4, respectively. MRI showed severe fatty
degeneration of the lateral pterygoid muscles that mediate mouth opening by
allowing mandibular condylar sliding but relatively mild involvement of the mouth
closing muscles in patients with reduced MMO. Reduced MMO was associated with SMA
type, age, muscle weakness, and dysphagia (p < 0.05). CONCLUSIONS: Reduced MMO is
common in SMA types 1-3a and is mainly caused by fatty degeneration of specific
mouth opening muscles. Reduced MMO is a sign of bulbar dysfunction in SMA.
PMID- 25122198
TI - The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving
components of the tumor microenvironment and promotes prostate cancer metastasis.
AB - TMPRSS2 is an androgen-regulated cell-surface serine protease expressed
predominantly in prostate epithelium. TMPRSS2 is expressed highly in localized
high-grade prostate cancers and in the majority of human prostate cancer
metastases. Through the generation of mouse models with a targeted deletion of
Tmprss2, we demonstrate that the activity of this protease regulates cancer cell
invasion and metastasis to distant organs. By screening combinatorial peptide
libraries, we identified a spectrum of TMPRSS2 substrates that include pro
hepatocyte growth factor (HGF). HGF activated by TMPRSS2 promoted c-MET receptor
tyrosine kinase signaling, and initiated a proinvasive epithelial-to-mesenchymal
transition phenotype. Chemical library screens identified a potent bioavailable
TMPRSS2 inhibitor that suppressed prostate cancer metastasis in vivo. Together,
these findings provide a mechanistic link between androgen-regulated signaling
programs and prostate cancer metastasis that operate via context-dependent
interactions with extracellular constituents of the tumor microenvironment.
SIGNIFICANCE: The vast majority of prostate cancer deaths are due to metastasis.
Loss of TMPRSS2 activity dramatically attenuated the metastatic phenotype through
mechanisms involving the HGF-c-MET axis. Therapeutic approaches directed toward
inhibiting TMPRSS2 may reduce the incidence or progression of metastasis in
patients with prostate cancer.
PMID- 25122202
TI - Aspirin for secondary prevention after stroke of unknown etiology in resource
limited settings.
AB - OBJECTIVE: To analyze the potential impact of aspirin therapy for long-term
secondary prevention after stroke of undetermined etiology in resource-limited
settings without access to neuroimaging to distinguish ischemic stroke from
intracerebral hemorrhage (ICH). METHODS: We conducted a decision analysis using a
Markov state transition model. Sensitivity analyses were performed across the
worldwide reported range of the proportion of strokes due to ICH and the 95%
confidence intervals (CIs) of aspirin-associated relative risks in patients with
ICH. RESULTS: For patients with stroke of undetermined etiology, long-term
aspirin was the preferred treatment strategy across the worldwide reported range
of the proportion of strokes due to ICH. At 34% of strokes due to ICH (the
highest proportion reported in a large epidemiologic study), the benefit of
aspirin remained beyond the upper bounds of the 95% CIs of aspirin-associated
post-ICH relative risks most concerning to clinicians (ICH recurrence risk and
mortality risk if ICH recurs on aspirin). Based on the estimated 11,590,204
strokes in low- and middle-income countries in 2010, our model predicts that
aspirin therapy for secondary stroke prevention in all patients with stroke in
these countries could lead to an estimated yearly decrease of 84,492 recurrent
strokes and 4,056 stroke-related mortalities. CONCLUSIONS: The concern that the
risks of aspirin in patients with stroke of unknown etiology could outweigh the
benefits is not supported by our model, which predicts that aspirin for secondary
prevention in patients with stroke of undetermined etiology in resource-limited
settings could lead to decreased stroke-related mortality and stroke recurrence.
PMID- 25122204
TI - Population-based incidence and prevalence of facioscapulohumeral dystrophy.
AB - OBJECTIVE: To determine the incidence and prevalence of facioscapulohumeral
muscular dystrophy (FSHD) in the Netherlands. METHODS: Using 3-source capture
recapture methodology, we estimated the total yearly number of newly found
symptomatic individuals with FSHD, including those not registered in any of the 3
sources. To this end, symptomatic individuals with FSHD were available from 3
large population-based registries in the Netherlands if diagnosed within a 10
year period (January 1, 2001 to December 31, 2010). Multiplication of the
incidence and disease duration delivered the prevalence estimate. RESULTS: On
average, 52 people are newly diagnosed with FSHD every year. This results in an
incidence rate of 0.3/100,000 person-years in the Netherlands. The prevalence
rate was 12/100,000, equivalent to 2,000 affected individuals. CONCLUSIONS: We
present population-based incidence and prevalence estimates regarding symptomatic
individuals with FSHD, including an estimation of the number of symptomatic
individuals not present in any of the 3 used registries. This study shows that
the total number of symptomatic persons with FSHD in the population may well be
underestimated and a considerable number of affected individuals remain
undiagnosed. This suggests that FSHD is one of the most prevalent neuromuscular
disorders.
PMID- 25122203
TI - The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia.
AB - OBJECTIVE: To assess the clinical spectrum of ataxia-telangiectasia (A-T) in
adults, with a focus on movement disorders. METHODS: A total of 14 consecutive
adults with A-T were included at 2 tertiary adult movement disorders centers and
compared to 53 typical patients with A-T. Clinical evaluation, neurophysiologic
and video-oculographic recording, imaging, laboratory investigations, and ATM
analysis were performed. RESULTS: In comparison with typical A-T cases, our
patients demonstrated later mean age at onset (6.1 vs 2.5 years, p < 0.0001),
later loss of walking ability (p = 0.003), and longer survival (p = 0.0039). The
presenting feature was ataxia in 71% and dysarthria and dystonia in 14% each. All
patients displayed movement disorders, among which dystonia and subcortical
myoclonus were the most common (86%), followed by tremor (43%). Video
oculographic recordings revealed mostly dysmetric saccades and 46% of patients
had normal latencies (i.e., no oculomotor apraxia) and velocities. The alpha
fetoprotein (AFP) level was normal in 7%, chromosomal instability was found in
29% (vs 100% of typical patients, p = 0.0006), and immunoglobulin deficiency was
found in 29% (vs 69%, p = 0.057). All patients exhibited 2 ATM mutations,
including at least 1 missense mutation in 79% of them (vs 36%, p = 0.0067).
CONCLUSION: There is great variability of phenotype and severity in A-T,
including a wide spectrum of movement disorders. Karyotype and repeated AFP level
assessments should be performed in adults with unexplained movement disorders as
valuable clues towards the diagnosis. In case of a compatible phenotype, A-T
should be considered even if age at onset is late and progression is slow.
PMID- 25122205
TI - Increased risk of osteoporosis in patients with myasthenia gravis: a population
based cohort study.
AB - OBJECTIVE: To determine the risk of osteoporosis in patients with myasthenia
gravis (MG) in a large cohort representing 99% of the population of Taiwan.
METHODS: Data from the Taiwan National Health Insurance Research Database were
used to conduct retrospective cohort analyses. The study cohort consisted of
2,073 patients with MG who were 3-fold frequency-matched by age and sex and
assigned the same index year as a comparison cohort without MG. Cox proportional
hazard regression analysis was conducted to estimate the risk of osteoporosis.
RESULTS: The MG cohort had a 1.96-fold increased risk of developing osteoporosis
compared with the comparison cohort (hazard ratio [HR] = 1.96, 95% confidence
interval [CI] = 1.57-2.44). Patients with MG older than 30 years developed an
increased risk of osteoporosis, with the highest risk in the age group from 30 to
44 years, compared with the control cohort. Corticosteroid-naive patients with MG
had a 1.52-fold increased risk of developing osteoporosis (HR = 1.52, 95% CI =
1.11-2.08), and the corticosteroid-treated cohort had a 2.37-fold increased risk
of developing osteoporosis (HR = 2.37, 95% CI = 1.82-3.07). CONCLUSION: This
population-based retrospective cohort study provides evidence that MG is
associated with a high risk of osteoporosis regardless of corticosteroid use.
PMID- 25122206
TI - Growth hormone treatment for childhood short stature and risk of stroke in early
adulthood.
AB - OBJECTIVES: We investigated the incidence of stroke and stroke subtypes in a
population-based cohort of patients in France treated with growth hormone (GH)
for short stature in childhood. METHODS: Adult morbidity data were obtained in
2008-2010 for 6,874 children with idiopathic isolated GH deficiency or short
stature who started GH treatment between 1985 and 1996. Cerebrovascular events
were validated using medical reports and imaging data and classified according to
standard definitions of subarachnoid hemorrhage, intracerebral hemorrhage, and
ischemic stroke. Case ascertainment completeness was estimated with capture
recapture methods. The incidence of stroke and of stroke subtypes was calculated
and compared with population values extracted from registries in Dijon and
Oxford, between 2000 and 2012. RESULTS: Using both Dijon and Oxford population
based registries as references, there was a significantly higher risk of stroke
among patients treated with GH in childhood. The excess risk of stroke was mainly
attributable to a very substantially and significantly higher risk of hemorrhagic
stroke (standardized incidence ratio from 3.5 to 7.0 according to the registry
rates considered, and accounting or not accounting for missed cases), and
particularly subarachnoid hemorrhage (standardized incidence ratio from 5.7 to
9.3). CONCLUSIONS: We report a strong relationship between hemorrhagic stroke and
GH treatment in childhood for isolated growth hormone deficiency or childhood
short stature. Patients treated with GH worldwide should be advised about this
association and further studies should evaluate the potentially causal role of GH
treatment in these findings.
PMID- 25122207
TI - Functional pattern of brain FDG-PET in amyotrophic lateral sclerosis.
AB - OBJECTIVE: We investigated a large sample of patients with amyotrophic lateral
sclerosis (ALS) at rest in order to assess the value of (18)F-2-fluoro-2-deoxy-d
glucose ((18)F-FDG) PET as a biomarker to discriminate patients from controls.
METHODS: A total of 195 patients with ALS and 40 controls underwent brain (18)F
FDG-PET, most within 5 months of diagnosis. Spinal and bulbar subgroups of ALS
were also investigated. Twenty-five bilateral cortical and subcortical volumes of
interest and cerebellum were taken into account, and (18)F-FDG uptakes were
individually normalized by whole-brain values. Group analyses investigated the
ALS-related metabolic changes. Discriminant analysis investigating sensitivity
and specificity was performed using the 51 volumes of interest as well as age and
sex. Metabolic connectivity was explored by voxel-wise interregional correlation
analysis. RESULTS: Hypometabolism was found in frontal, motor, and occipital
cortex and hypermetabolism in midbrain, temporal pole, and hippocampus in
patients with ALS compared to controls. A similar metabolic pattern was also
found in the 2 subgroups. Discriminant analysis showed a sensitivity of 95% and a
specificity of 83% in separating patients from controls. Connectivity analysis
found a highly significant positive correlation between midbrain and white matter
in corticospinal tracts in patients with ALS. CONCLUSIONS: (18)F-FDG distribution
changes in ALS showed a clear pattern of hypometabolism in frontal and occipital
cortex and hypermetabolism in midbrain. The latter might be interpreted as the
neurobiological correlate of diffuse subcortical gliosis. Discriminant analysis
resulted in high sensitivity and specificity in differentiating patients with ALS
from controls. Once validated by diseased-control studies, the present
methodology might represent a potentially useful biomarker for ALS diagnosis.
CLASSIFICATON OF EVIDENCE: This study provides Class III evidence that (18)F-FDG
PET accurately distinguishes patients with ALS from normal controls (sensitivity
95.4%, specificity 82.5%).
PMID- 25122208
TI - A transposable element insertion confers xenobiotic resistance in Drosophila.
AB - The increase in availability of whole genome sequences makes it possible to
search for evidence of adaptation at an unprecedented scale. Despite recent
progress, our understanding of the adaptive process is still very limited due to
the difficulties in linking adaptive mutations to their phenotypic effects. In
this study, we integrated different levels of biological information to pinpoint
the ecologically relevant fitness effects and the underlying molecular and
biochemical mechanisms of a putatively adaptive TE insertion in Drosophila
melanogaster: the pogo transposon FBti0019627. We showed that other than being
incorporated into Kmn1 transcript, FBti0019627 insertion also affects the
polyadenylation signal choice of CG11699 gene. Consequently, only the short 3'UTR
transcript of CG11699 gene is produced and the expression level of this gene is
higher in flies with the insertion. Our results indicated that increased CG11699
expression leads to xenobiotic stress resistance through increased ALDH-III
activity: flies with FBti0019627 insertion showed increased survival rate in
response to benzaldehyde, a natural xenobiotic, and to carbofuran, a synthetic
insecticide. Although differences in survival rate between flies with and without
the insertion were not always significant, when they were, they were consistent
with FBti0019627 mediating resistance to xenobiotics. Taken together, our results
provide a plausible explanation for the increase in frequency of FBti0019627 in
natural populations of D. melanogaster and add to the limited number of examples
in which a natural genetic mutation has been linked to its ecologically relevant
phenotype. Furthermore, the widespread distribution of TEs across the tree of
life and conservation of stress response pathways across organisms make our
results relevant not only for Drosophila, but for other organisms as well.
PMID- 25122209
TI - A scalable and accurate targeted gene assembly tool (SAT-Assembler) for next
generation sequencing data.
AB - Gene assembly, which recovers gene segments from short reads, is an important
step in functional analysis of next-generation sequencing data. Lacking quality
reference genomes, de novo assembly is commonly used for RNA-Seq data of non
model organisms and metagenomic data. However, heterogeneous sequence coverage
caused by heterogeneous expression or species abundance, similarity between
isoforms or homologous genes, and large data size all pose challenges to de novo
assembly. As a result, existing assembly tools tend to output fragmented contigs
or chimeric contigs, or have high memory footprint. In this work, we introduce a
targeted gene assembly program SAT-Assembler, which aims to recover gene families
of particular interest to biologists. It addresses the above challenges by
conducting family-specific homology search, homology-guided overlap graph
construction, and careful graph traversal. It can be applied to both RNA-Seq and
metagenomic data. Our experimental results on an Arabidopsis RNA-Seq data set and
two metagenomic data sets show that SAT-Assembler has smaller memory usage,
comparable or better gene coverage, and lower chimera rate for assembling a set
of genes from one or multiple pathways compared with other assembly tools.
Moreover, the family-specific design and rapid homology search allow SAT
Assembler to be naturally compatible with parallel computing platforms. The
source code of SAT-Assembler is available at https://sourceforge.net/projects/sat
assembler/. The data sets and experimental settings can be found in supplementary
material.
PMID- 25122210
TI - IL-31 associated with coronary artery lesion formation in Kawasaki disease.
AB - BACKGROUND: Kawasaki disease (KD) is known to be associated with T help (Th) 2
reaction and subsequently allergic diseases. Interleukin-31 (IL-31) has also been
reported to be involved in Th2 mediated diseases such as allergic diseases.
However, the role of IL-31 in KD has not been previously reported. The aim of
this study is to investigate whether IL-31 is associated with KD and its clinical
outcome. MATERIAL: A total of 78 KD patients who met the criteria of KD were
enrolled in this study as well as 20 age-matched controls. Plasma samples were
conducted to measure IL-31 before intravenous immunoglobulin (IVIG) treatment
(KD1), within 3 days after IVIG treatment (KD2) and at least 3 weeks after IVIG
treatment (KD3) by utilizing enzyme-linked immunosorbent assay (ELISA). RESULT:
Our findings showed that IL-31 expression was higher in KD patients after IVIG
treatment significantly (KD2>KD1: 1265.0+/-199.3 vs. 840.2+/-152.5 pg/ml,
p<0.0001). Further analysis revealed that IL-31 level was significantly higher in
KD patients with coronary artery lesion (CAL) (656.6+/-139.5 vs. 1373.0+/-422.0
pg/ml, p = 0.04) before IVIG treatment (KD1). There were no significant
differences between the IVIG resistance and IVIG responsiveness groups.
CONCLUSION: IL-31 was increased after IVIG treatment in patients with KD and was
significantly associated with CAL formation. The results from this study may help
to identify a novel risk factor for predicting KD and CAL formation.
PMID- 25122211
TI - In-cell intrabody selection from a diverse human library identifies C12orf4
protein as a new player in rodent mast cell degranulation.
AB - The high specificity of antibodies for their antigen allows a fine discrimination
of target conformations and post-translational modifications, making antibodies
the first choice tool to interrogate the proteome. We describe here an approach
based on a large-scale intracellular expression and selection of antibody
fragments in eukaryotic cells, so-called intrabodies, and the subsequent
identification of their natural target within living cell. Starting from a
phenotypic trait, this integrated system allows the identification of new
therapeutic targets together with their companion inhibitory intrabody. We
applied this system in a model of allergy and inflammation. We first cloned a
large and highly diverse intrabody library both in a plasmid and a retroviral
eukaryotic expression vector. After transfection in the RBL-2H3 rat basophilic
leukemia cell line, we performed seven rounds of selection to isolate cells
displaying a defect in FcepsilonRI-induced degranulation. We used high throughput
sequencing to identify intrabody sequences enriched during the course of
selection. Only one intrabody was common to both plasmid and retroviral
selections, and was used to capture and identify its target from cell extracts.
Mass spectrometry analysis identified protein RGD1311164 (C12orf4), with no
previously described function. Our data demonstrate that RGD1311164 is a
cytoplasmic protein implicated in the early signaling events following
FcepsilonRI-induced cell activation. This work illustrates the strength of the
intrabody-based in-cell selection, which allowed the identification of a new
player in mast cell activation together with its specific inhibitor intrabody.
PMID- 25122214
TI - Evidence for two types of lateral interactions in visual perception of temporal
signals.
AB - The aim of this work was to investigate the mechanisms of lateral interactions
involved in flicker perception. Furthermore, the spatial properties of the
monoptic and dichoptic components of these mechanisms were studied. We quantified
the perceived flicker strength (PFS) in the center of a test stimulus, which was
simultaneously modulated with a surround stimulus of variable size. The
modulation depth of a separate stimulus, identical to the center test stimulus
but without the surround, was determined using a two-alternative forced choice
procedure. Using LCD goggles synchronized to the frame rate of a CRT screen, the
center and surround of the test stimulus were presented either monoptically or
dichoptically. In the monoptic condition, center-surround interactions have
subcortical and cortical origins. In the dichoptic condition, center-surround
interactions must have a cortical origin. The difference between the dichoptic
and the monoptic data is an estimate of the contribution of the subcortical
mechanisms. At each condition (surround stimulus size; monoptic or dichoptic
presentation), the PFS was measured for phase differences between center and
surround stimuli. The PFS changed systematically with phase difference. It also
was observed that the PFS in the center stimulus changed merely be the presence
of a surround stimulus independently of the center-surround phase difference. We
propose that this is a phase-independent mechanism related to contrast adaptation
owing to the presence of surround modulation. Our data suggest that both phase
dependent and -independent mechanisms have cortical and subcortical origins.
There were no systematic differences between the spatial properties of
subcortical and cortical components involved in PFS modulation.
PMID- 25122213
TI - Scaling-up access to antiretroviral therapy for children: a cohort study
evaluating care and treatment at mobile and hospital-affiliated HIV clinics in
rural Zambia.
AB - BACKGROUND: Travel time and distance are barriers to care for HIV-infected
children in rural sub-Saharan Africa. Decentralization of care is one strategy to
scale-up access to antiretroviral therapy (ART), but few programs have been
evaluated. We compared outcomes for children receiving care in mobile and
hospital-affiliated HIV clinics in rural Zambia. METHODS: Outcomes were measured
within an ongoing cohort study of HIV-infected children seeking care at Macha
Hospital, Zambia from 2007 to 2012. Children in the outreach clinic group
received care from the Macha HIV clinic and transferred to one of three outreach
clinics. Children in the hospital-affiliated clinic group received care at Macha
HIV clinic and reported Macha Hospital as the nearest healthcare facility.
RESULTS: Seventy-seven children transferred to the outreach clinics and were
included in the analysis. Travel time to the outreach clinics was significantly
shorter and fewer caretakers used public transportation, resulting in lower
transportation costs and fewer obstacles accessing the clinic. Some caretakers
and health care providers reported inferior quality of service provision at the
outreach clinics. Sixty-eight children received ART at the outreach clinics and
were compared to 41 children in the hospital-affiliated clinic group. At ART
initiation, median age, weight-for-age z-scores (WAZ) and CD4(+) T-cell
percentages were similar for children in the hospital-affiliated and outreach
clinic groups. Children in both groups experienced similar increases in WAZ and
CD4(+) T-cell percentages. CONCLUSIONS: HIV care and treatment can be effectively
delivered to HIV-infected children at rural health centers through mobile ART
teams, removing potential barriers to uptake and retention. Outreach teams should
be supported to increase access to HIV care and treatment in rural areas.
PMID- 25122212
TI - The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope
protein is a determinant of viral pathogenesis.
AB - A recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) lacking
the envelope (E) protein is attenuated in vivo. Here we report that E protein PDZ
binding motif (PBM), a domain involved in protein-protein interactions, is a
major determinant of virulence. Elimination of SARS-CoV E protein PBM by using
reverse genetics caused a reduction in the deleterious exacerbation of the immune
response triggered during infection with the parental virus and virus
attenuation. Cellular protein syntenin was identified to bind the E protein PBM
during SARS-CoV infection by using three complementary strategies, yeast two
hybrid, reciprocal coimmunoprecipitation and confocal microscopy assays. Syntenin
redistributed from the nucleus to the cell cytoplasm during infection with
viruses containing the E protein PBM, activating p38 MAPK and leading to the
overexpression of inflammatory cytokines. Silencing of syntenin using siRNAs led
to a decrease in p38 MAPK activation in SARS-CoV infected cells, further
reinforcing their functional relationship. Active p38 MAPK was reduced in lungs
of mice infected with SARS-CoVs lacking E protein PBM as compared with the
parental virus, leading to a decreased expression of inflammatory cytokines and
to virus attenuation. Interestingly, administration of a p38 MAPK inhibitor led
to an increase in mice survival after infection with SARS-CoV, confirming the
relevance of this pathway in SARS-CoV virulence. Therefore, the E protein PBM is
a virulence domain that activates immunopathology most likely by using syntenin
as a mediator of p38 MAPK induced inflammation.
PMID- 25122215
TI - Encoding of configural regularity in the human visual system.
AB - The visual system is very efficient in encoding stimulus properties by utilizing
available regularities in the inputs. To explore the underlying encoding
strategies during visual information processing, we presented participants with
two-line configurations that varied in the amount of configural regularity (or
degrees of freedom in the relative positioning of the two lines) in a fMRI
experiment. Configural regularity ranged from a generic configuration to stimuli
resembling an "L" (i.e., a right-angle L-junction), a "T" (i.e., a right-angle
midpoint T-junction), or a "+",-the latter being the most regular stimulus. We
found that the response strength in the shape-selective lateral occipital area
was consistently lower for a higher degree of regularity in the stimuli. In the
second experiment, using multivoxel pattern analysis, we further show that
regularity is encoded in terms of the fMRI signal strength but not in the
distributed pattern of responses. Finally, we found that the results of these
experiments could not be accounted for by low-level stimulus properties and are
distinct from norm-based encoding. Our results suggest that regularity plays an
important role in stimulus encoding in the ventral visual processing stream.
PMID- 25122216
TI - Accuracy and speed of material categorization in real-world images.
AB - It is easy to visually distinguish a ceramic knife from one made of steel, a
leather jacket from one made of denim, and a plush toy from one made of plastic.
Most studies of material appearance have focused on the estimation of specific
material properties such as albedo or surface gloss, and as a consequence, almost
nothing is known about how we recognize material categories like leather or
plastic. We have studied judgments of high-level material categories with a
diverse set of real-world photographs, and we have shown (Sharan, 2009) that
observers can categorize materials reliably and quickly. Performance on our tasks
cannot be explained by simple differences in color, surface shape, or texture.
Nor can the results be explained by observers merely performing shape-based
object recognition. Rather, we argue that fast and accurate material
categorization is a distinct, basic ability of the visual system.
PMID- 25122217
TI - Exploring heterozygosity-survival correlations in a wild songbird population:
contrasting effects between juvenile and adult stages.
AB - The relationship between genetic diversity and fitness, a major issue in
evolutionary and conservation biology, is expected to be stronger in traits
affected by many loci and those directly influencing fitness. Here we explore the
influence of heterozygosity measured at 15 neutral markers on individual
survival, one of the most important parameters determining individual fitness. We
followed individual survival up to recruitment and during subsequent adult life
of 863 fledgling pied flycatchers born in two consecutive breeding seasons. Mark
recapture analyses showed that individual heterozygosity did not influence
juvenile or adult survival. In contrast, the genetic relatedness of parents was
negatively associated with the offspring's survival during the adult life, but
this effect was not apparent in the juvenile (from fledgling to recruitment)
stage. Stochastic factors experienced during the first year of life in this long
distance migratory species may have swamped a relationship between heterozygosity
and survival up to recruitment.
PMID- 25122218
TI - Improving children's oral health: an interdisciplinary research framework.
AB - Despite the concerted efforts of research and professional and advocacy
stakeholders, recent evidence suggests that improvements in the oral health of
young children in the United States has not followed the prevailing trend of oral
health improvement in other age groups. In fact, oral health disparities in the
youngest children may be widening, yet efforts to translate advances in science
and technology into meaningful improvements in populations' health have had
limited success. Nevertheless, the great strides in genomics, biological,
behavioral, social, and health services research in the past decade have
strengthened the evidence base available to support initiatives and translational
efforts. Concerted actions to accelerate this translation and implementation
process are warranted; at the same time, policies that can help tackle the
upstream determinants of oral health disparities are imperative. This article
summarizes the proceedings from the symposium on the interdisciplinary continuum
of pediatric oral health that was held during the 43rd annual meeting of the
American Association for Dental Research, Charlotte, North Carolina, USA. This
report showcases the latest contributions across the interdisciplinary continuum
of pediatric oral health research and provides insights into future research
priorities and necessary intersectoral synergies. Issues are discussed as related
to the overwhelming dominance of social determinants on oral disease and the
difficulty of translating science into action.
PMID- 25122220
TI - Quantifying the role of population subdivision in evolution on rugged fitness
landscapes.
AB - Natural selection drives populations towards higher fitness, but crossing fitness
valleys or plateaus may facilitate progress up a rugged fitness landscape
involving epistasis. We investigate quantitatively the effect of subdividing an
asexual population on the time it takes to cross a fitness valley or plateau. We
focus on a generic and minimal model that includes only population subdivision
into equivalent demes connected by global migration, and does not require
significant size changes of the demes, environmental heterogeneity or specific
geographic structure. We determine the optimal speedup of valley or plateau
crossing that can be gained by subdivision, if the process is driven by the deme
that crosses fastest. We show that isolated demes have to be in the sequential
fixation regime for subdivision to significantly accelerate crossing. Using
Markov chain theory, we obtain analytical expressions for the conditions under
which optimal speedup is achieved: valley or plateau crossing by the subdivided
population is then as fast as that of its fastest deme. We verify our analytical
predictions through stochastic simulations. We demonstrate that subdivision can
substantially accelerate the crossing of fitness valleys and plateaus in a wide
range of parameters extending beyond the optimal window. We study the effect of
varying the degree of subdivision of a population, and investigate the trade-off
between the magnitude of the optimal speedup and the width of the parameter range
over which it occurs. Our results, obtained for fitness valleys and plateaus,
also hold for weakly beneficial intermediate mutations. Finally, we extend our
work to the case of a population connected by migration to one or several smaller
islands. Our results demonstrate that subdivision with migration alone can
significantly accelerate the crossing of fitness valleys and plateaus, and shed
light onto the quantitative conditions necessary for this to occur.
PMID- 25122221
TI - Clonal expansion of the Pseudogymnoascus destructans genotype in North America is
accompanied by significant variation in phenotypic expression.
AB - Pseudogymnoascus destructans is the causative agent of an emerging infectious
disease that threatens populations of several North American bat species. The
fungal disease was first observed in 2006 and has since caused the death of
nearly six million bats. The disease, commonly known as white-nose syndrome, is
characterized by a cutaneous infection with P. destructans causing erosions and
ulcers in the skin of nose, ears and/or wings of bats. Previous studies based on
sequences from eight loci have found that isolates of P. destructans from bats in
the US all belong to one multilocus genotype. Using the same multilocus sequence
typing method, we found that isolates from eastern and central Canada also had
the same genotype as those from the US, consistent with the clonal expansion of
P. destructans into Canada. However, our PCR fingerprinting revealed that among
the 112 North American isolates we analyzed, three, all from Canada, showed minor
genetic variation. Furthermore, we found significant variations among isolates in
mycelial growth rate; the production of mycelial exudates; and pigment production
and diffusion into agar media. These phenotypic differences were influenced by
culture medium and incubation temperature, indicating significant variation in
environmental condition--dependent phenotypic expression among isolates of the
clonal P. destructans genotype in North America.
PMID- 25122222
TI - Long-term sonographic and serological follow-up of inactive echinococcal cysts of
the liver: hints for a "watch-and-wait" approach.
AB - Human cystic echinococcosis is a chronic, complex and neglected infection. Its
clinical management has evolved over decades without adequate evaluation of
efficacy. Recent expert opinion recommends that uncomplicated inactive cysts of
the liver should be left untreated and solely monitored over time ("watch-and
wait" approach). However, clinical data supporting this approach are still scant
and published mostly as conference proceedings. In this study, we report our
experience with long-term sonographic and serological follow-up of inactive cysts
of the liver. From March 1994 to October 2013, 38 patients with 47 liver cysts,
diagnosed as inactive without any previous treatment history, were followed with
ultrasound and serology at 6-12 months intervals for a period of at least 24
months (median follow-up 51.95 months) in our outpatient clinic. In 97.4% of
patients, the cysts remained inactive over time and in only one case was
reactivation of the cyst detected. No complications occurred during the time of
monitoring. During follow-up, serology tests for CE were negative at diagnosis or
became negative in 74.1% and were positive or became positive in 25.9% of cases.
Patients with inactive cysts on ultrasound but positive serological tests were
also investigated by CT scan (chest and abdomen) to rule out extra-hepatic cyst
localization. This study confirms the importance of a stage-specific approach to
the management of cystic echinococcosis and supports the use of a monitoring-only
approach to inactive, uncomplicated cysts of the liver. It also confirms that
serology plays only an ancillary role in the clinical management of these
patients, compared to ultrasound and other imaging techniques. The implications
of these findings for clinical management and natural history of cystic
echinococcosis are discussed.
PMID- 25122219
TI - Histone deacetylase inhibitors impair the elimination of HIV-infected cells by
cytotoxic T-lymphocytes.
AB - Resting memory CD4+ T-cells harboring latent HIV proviruses represent a critical
barrier to viral eradication. Histone deacetylase inhibitors (HDACis), such as
suberanilohydroxamic acid (SAHA), romidepsin, and panobinostat have been shown to
induce HIV expression in these resting cells. Recently, it has been demonstrated
that the low levels of viral gene expression induced by a candidate HDACi may be
insufficient to cause the death of infected cells by viral cytopathic effects,
necessitating their elimination by immune effectors, such as cytotoxic T
lymphocytes (CTL). Here, we study the impact of three HDACis in clinical
development on T-cell effector functions. We report two modes of HDACi-induced
functional impairment: i) the rapid suppression of cytokine production from
viable T-cells induced by all three HDACis ii) the selective death of activated T
cells occurring at later time-points following transient exposures to romidepsin
or, to a lesser extent, panobinostat. As a net result of these factors, HDACis
impaired CTL-mediated IFN-gamma production, as well as the elimination of HIV
infected or peptide-pulsed target cells, both in liquid culture and in collagen
matrices. Romidepsin exerted greater inhibition of antiviral function than SAHA
or panobinostat over the dose ranges tested. These data suggest that treatment
with HDACis to mobilize the latent reservoir could have unintended negative
impacts on the effector functions of CTL. This could influence the effectiveness
of HDACi-based eradication strategies, by impairing elimination of infected
cells, and is a critical consideration for trials where therapeutic interruptions
are being contemplated, given the importance of CTL in containing rebound
viremia.
PMID- 25122223
TI - Temporally dynamic habitat suitability predicts genetic relatedness among
caribou.
AB - Landscape heterogeneity plays a central role in shaping ecological and
evolutionary processes. While species utilization of the landscape is usually
viewed as constant within a year, the spatial distribution of individuals is
likely to vary in time in relation to particular seasonal needs. Understanding
temporal variation in landscape use and genetic connectivity has direct
conservation implications. Here, we modelled the daily use of the landscape by
caribou in Quebec and Labrador, Canada and tested its ability to explain the
genetic relatedness among individuals. We assessed habitat selection using
locations of collared individuals in migratory herds and static occurrences from
sedentary groups. Connectivity models based on habitat use outperformed a
baseline isolation-by-distance model in explaining genetic relatedness,
suggesting that variations in landscape features such as snow, vegetation
productivity and land use modulate connectivity among populations. Connectivity
surfaces derived from habitat use were the best predictors of genetic
relatedness. The relationship between connectivity surface and genetic
relatedness varied in time and peaked during the rutting period. Landscape
permeability in the period of mate searching is especially important to allow
gene flow among populations. Our study highlights the importance of considering
temporal variations in habitat selection for optimizing connectivity across
heterogeneous landscape and counter habitat fragmentation.
PMID- 25122224
TI - Hox gene duplications correlate with posterior heteronomy in scorpions.
AB - The evolutionary success of the largest animal phylum, Arthropoda, has been
attributed to tagmatization, the coordinated evolution of adjacent metameres to
form morphologically and functionally distinct segmental regions called tagmata.
Specification of regional identity is regulated by the Hox genes, of which 10 are
inferred to be present in the ancestor of arthropods. With six different
posterior segmental identities divided into two tagmata, the bauplan of scorpions
is the most heteronomous within Chelicerata. Expression domains of the anterior
eight Hox genes are conserved in previously surveyed chelicerates, but it is
unknown how Hox genes regionalize the three tagmata of scorpions. Here, we show
that the scorpion Centruroides sculpturatus has two paralogues of all Hox genes
except Hox3, suggesting cluster and/or whole genome duplication in this arachnid
order. Embryonic anterior expression domain boundaries of each of the last four
pairs of Hox genes (two paralogues each of Antp, Ubx, abd-A and Abd-B) are unique
and distinguish segmental groups, such as pectines, book lungs and the
characteristic tail, while maintaining spatial collinearity. These distinct
expression domains suggest neofunctionalization of Hox gene paralogues subsequent
to duplication. Our data reconcile previous understanding of Hox gene function
across arthropods with the extreme heteronomy of scorpions.
PMID- 25122225
TI - Maternal exposure to predator scents: offspring phenotypic adjustment and
dispersal.
AB - Predation is a strong selective pressure generating morphological, physiological
and behavioural responses in organisms. As predation risk is often higher during
juvenile stages, antipredator defences expressed early in life are paramount to
survival. Maternal effects are an efficient pathway to produce such defences. We
investigated whether maternal exposure to predator cues during gestation affected
juvenile morphology, behaviour and dispersal in common lizards (Zootoca
vivipara). We exposed 21 gravid females to saurophagous snake cues for one month
while 21 females remained unexposed (i.e. control). We measured body size,
preferred temperature and activity level for each neonate, and released them into
semi-natural enclosures connected to corridors in order to measure dispersal.
Offspring from exposed mothers grew longer tails, selected lower temperatures and
dispersed thrice more than offspring from unexposed mothers. Because both tail
autotomy and altered thermoregulatory behaviour are common antipredator tactics
in lizards, these results suggest that mothers adjusted offspring phenotype to
risky natal environments (tail length) or increased risk avoidance (dispersal).
Although maternal effects can be passive consequences of maternal stress, our
results strongly militate for them to be an adaptive antipredator response that
may increase offspring survival prospects.
PMID- 25122226
TI - Early life expenditure in sexual competition is associated with increased
reproductive senescence in male red deer.
AB - The evolutionary theories of senescence predict that investment in reproduction
in early life should come at the cost of reduced somatic maintenance, and thus
earlier or more rapid senescence. There is now growing support for such trade
offs in wild vertebrates, but these exclusively come from females. Here, we test
this prediction in male red deer (Cervus elaphus) using detailed longitudinal
data collected over a 40-year field study. We show that males which had larger
harems and thereby allocated more resources to reproduction during early
adulthood experienced higher rates of senescence in both harem size and rut
duration. Males that carried antlers with more points during early life did not
show more pronounced declines in reproductive traits in later life. Overall, we
demonstrate that sexual competition shapes male reproductive senescence in wild
red deer populations and provide rare empirical support for the disposable soma
theory of ageing in males of polygynous vertebrate species.
PMID- 25122227
TI - Cryptic cuckoo eggs hide from competing cuckoos.
AB - Interspecific arms races between cuckoos and their hosts have produced remarkable
examples of mimicry, with parasite eggs evolving to match host egg appearance and
so evade removal by hosts. Certain bronze-cuckoo species, however, lay eggs that
are cryptic rather than mimetic. These eggs are coated in a low luminance pigment
that camouflages them within the dark interiors of hosts' nests. We investigated
whether cuckoo egg crypsis is likely to have arisen from the same coevolutionary
processes known to favour egg mimicry. We added high and low luminance-painted
eggs to the nests of large-billed gerygones (Gerygone magnirostris), a host of
the little bronze-cuckoo (Chalcites minutillus). Gerygones rarely rejected either
egg type, and did not reject natural cuckoo eggs. Cuckoos, by contrast, regularly
removed an egg from clutches before laying their own and were five times more
likely to remove a high luminance model than its low luminance counterpart. Given
that we found one-third of all parasitized nests were exploited by multiple
cuckoos, our results suggest that competition between cuckoos has been the key
selective agent for egg crypsis. In such intraspecific arms races, crypsis may be
favoured over mimicry because it can reduce the risk of egg removal to levels
below chance.
PMID- 25122229
TI - Contrasting effects of large density changes on relative testes size in
fluctuating populations of sympatric vole species.
AB - Across species, there is usually a positive relationship between sperm
competition level and male reproductive effort on ejaculates, typically measured
using relative testes size (RTS). Within populations, demographic and ecological
processes may drastically alter the level of sperm competition and thus,
potentially affect the evolution of testes size. Here, we use longitudinal
records (across 38 years) from wild sympatric Fennoscandian populations of five
species of voles to investigate whether RTS responds to natural fluctuations in
population density, i.e. variation in sperm competition risk. We show that for
some species RTS increases with density. However, our results also show that this
relationship can be reversed in populations with large-scale between-year
differences in density. Multiple mechanisms are suggested to explain the negative
RTS-density relationship, including testes size response to density-dependent
species interactions, an evolutionary response to sperm competition levels that
is lagged when density fluctuations are over a certain threshold, or differing
investment in pre- and post-copulatory competition at different densities. The
results emphasize that our understanding of sperm competition in fluctuating
environments is still very limited.
PMID- 25122228
TI - Three-way interactions between mosquito population, viral strain and temperature
underlying chikungunya virus transmission potential.
AB - Interactions between pathogens and their insect vectors in nature are under the
control of both genetic and non-genetic factors, yet most studies on mosquito
vector competence for human pathogens are conducted in laboratory systems that do
not consider genetic and/or environmental variability. Evaluating the risk of
emergence of arthropod-borne viruses (arboviruses) of public health importance
such as chikungunya virus (CHIKV) requires a more realistic appraisal of genetic
and environmental contributions to vector competence. In particular, sources of
variation do not necessarily act independently and may combine in the form of
interactions. Here, we measured CHIKV transmission potential by the mosquito
Aedes albopictus in all combinations of six worldwide vector populations, two
virus strains and two ambient temperatures (20 degrees C and 28 degrees C).
Overall, CHIKV transmission potential by Ae. albopictus strongly depended on the
three-way combination of mosquito population, virus strain and temperature. Such
genotype-by-genotype-by-environment (G * G * E) interactions question the
relevance of vector competence studies conducted with a simpler set of
conditions. Our results highlight the need to account for the complex interplay
between vectors, pathogens and environmental factors to accurately assess the
potential of vector-borne diseases to emerge.
PMID- 25122230
TI - Genetic elimination of field-cage populations of Mediterranean fruit flies.
AB - The Mediterranean fruit fly (medfly, Ceratitis capitata Wiedemann) is a pest of
over 300 fruits, vegetables and nuts. The sterile insect technique (SIT) is a
control measure used to reduce the reproductive potential of populations through
the mass release of sterilized male insects that mate with wild females. However,
SIT flies can display poor field performance, due to the effects of mass-rearing
and of the irradiation process used for sterilization. The development of female
lethal RIDL (release of insects carrying a dominant lethal) strains for medfly
can overcome many of the problems of SIT associated with irradiation. Here, we
present life-history characterizations for two medfly RIDL strains, OX3864A and
OX3647Q. Our results show (i) full functionality of RIDL, (ii) equivalency of
RIDL and wild-type strains for life-history characteristics, and (iii) a high
level of sexual competitiveness against both wild-type and wild-derived males. We
also present the first proof-of-principle experiment on the use of RIDL to
eliminate medfly populations. Weekly releases of OX3864A males into stable
populations of wild-type medfly caused a successive decline in numbers, leading
to eradication. The results show that genetic control can provide an effective
alternative to SIT for the control of pest insects.
PMID- 25122231
TI - Prediction of phylogeographic endemism in an environmentally complex biome.
AB - Phylogeographic endemism, the degree to which the history of recently evolved
lineages is spatially restricted, reflects fundamental evolutionary processes
such as cryptic divergence, adaptation and biological responses to environmental
heterogeneity. Attempts to explain the extraordinary diversity of the tropics,
which often includes deep phylogeographic structure, frequently invoke
interactions of climate variability across space, time and topography. To
evaluate historical versus contemporary drivers of phylogeographic endemism in a
tropical system, we analyse the effects of current and past climatic variation on
the genetic diversity of 25 vertebrates in the Brazilian Atlantic rainforest. We
identify two divergent bioclimatic domains within the forest and high turnover
around the Rio Doce. Independent modelling of these domains demonstrates that
endemism patterns are subject to different climatic drivers. Past climate
dynamics, specifically areas of relative stability, predict phylogeographic
endemism in the north. Conversely, contemporary climatic heterogeneity better
explains endemism in the south. These results accord with recent speleothem and
fossil pollen studies, suggesting that climatic variability through the last 250
kyr impacted the northern and the southern forests differently. Incorporating sub
regional differences in climate dynamics will enhance our ability to understand
those processes shaping high phylogeographic and species endemism, in the
Neotropics and beyond.
PMID- 25122232
TI - Facial fluctuating asymmetry is not associated with childhood ill-health in a
large British cohort study.
AB - The idea that symmetry in facial traits is associated with attractiveness because
it reliably indicates good physiological health, particularly to potential sexual
partners, has generated an extensive literature on the evolution of human mate
choice. However, large-scale tests of this hypothesis using direct or
longitudinal assessments of physiological health are lacking. Here, we
investigate relationships between facial fluctuating asymmetry (FA) and detailed
individual health histories in a sample (n = 4732) derived from a large
longitudinal study (Avon Longitudinal Study of Parents and Children) in South
West England. Facial FA was assessed using geometric morphometric analysis of
facial landmark configurations derived from three-dimensional facial scans taken
at 15 years of age. Facial FA was not associated with longitudinal measures of
childhood health. However, there was a very small negative association between
facial FA and IQ that remained significant after correcting for a positive
allometric relationship between FA and face size. Overall, this study does not
support the idea that facial symmetry acts as a reliable cue to physiological
health. Consequently, if preferences for facial symmetry do represent an evolved
adaptation, then they probably function not to provide marginal fitness benefits
by choosing between relatively healthy individuals on the basis of small
differences in FA, but rather evolved to motivate avoidance of markers of
substantial developmental disturbance and significant pathology.
PMID- 25122234
TI - Consistent inference of a general model using the pseudolikelihood method.
AB - Recently, a maximum pseudolikelihood (MPL) inference method has been successfully
applied to statistical physics models with intractable likelihoods. We use
information theory to derive a relation between the pseudolikelihood and
likelihood functions. Furthermore, we show the consistency of the
pseudolikelihood method for a general model.
PMID- 25122233
TI - Costs for switching partners reduce network dynamics but not cooperative
behaviour.
AB - Social networks represent the structuring of interactions between group members.
Above all, many interactions are profoundly cooperative in humans and other
animals. In accordance with this natural observation, theoretical work
demonstrates that certain network structures favour the evolution of cooperation.
Yet, recent experimental evidence suggests that static networks do not enhance
cooperative behaviour in humans. By contrast, dynamic networks do foster
cooperation. However, costs associated with dynamism such as time or resource
investments in finding and establishing new partnerships have been neglected so
far. Here, we show that human participants are much less likely to break links
when costs arise for building new links. Especially, when costs were high, the
network was nearly static. Surprisingly, cooperation levels in Prisoner's Dilemma
games were not affected by reduced dynamism in social networks. We conclude that
the mere potential to quit collaborations is sufficient in humans to reach high
levels of cooperative behaviour. Effects of self-structuring processes or
assortment on the network played a minor role: participants simply adjusted their
cooperative behaviour in response to the threats of losing a partner or of being
expelled.
PMID- 25122235
TI - Particle diagrams and embedded many-body random matrix theory.
AB - We present a method which uses Feynman-like diagrams to calculate the statistical
quantities of embedded many-body random matrix problems. The method provides a
promising alternative to existing techniques and offers many important
simplifications. We use it here to find the fourth, sixth, and eighth moments of
the level density of an m-body system with k fermions or bosons interacting
through a random Hermitian potential (k <= m) in the limit where the number of
possible single-particle states is taken to infinity. All share the same
transition, starting immediately after 2k = m, from moments arising from a
semicircular level density to Gaussian moments. The results also reveal a
striking feature; the domain of the 2nth moment is naturally divided into n
subdomains specified by the points 2k = m,3 k = m,...,nk = m.
PMID- 25122236
TI - Anomalous preasymptotic colloid transport by hydrodynamic dispersion in
microfluidic capillary flow.
AB - The anomalous preasymptotic transport of colloids in a microfluidic capillary
flow due to hydrodynamic dispersion is measured by noninvasive nuclear magnetic
resonance (NMR). The data indicate a reduced scaling of mean squared displacement
with time from the (c) ~ t(3) behavior for the interaction of a normal
diffusion process with a simple shear flow. This nonequilibrium steady-state
system is shown to be modeled by a continuous time random walk (CTRW) on a moving
fluid. The full propagator of the motion is measured by NMR, providing
verification of the assumption of Gaussian jump length distributions in the CTRW
model. The connection of the data to microrheology measurements by NMR, in which
every particle in a suspension contributes information, is established.
PMID- 25122239
TI - Derivation of a neural field model from a network of theta neurons.
AB - Neural field models are used to study macroscopic spatiotemporal patterns in the
cortex. Their derivation from networks of model neurons normally involves a
number of assumptions, which may not be correct. Here we present an exact
derivation of a neural field model from an infinite network of theta neurons, the
canonical form of a type I neuron. We demonstrate the existence of a "bump"
solution in both a discrete network of neurons and in the corresponding neural
field model.
PMID- 25122237
TI - Effective attenuation length of an electron in liquid water between 10 and 600
eV.
AB - The absolute values of the effective attenuation length of an electron in liquid
water are determined using soft x-ray O1s photoemission spectroscopy of a liquid
beam of water without employing any theoretical estimation or computationally
obtained value. The effective attenuation length is greater than 1 nm in the
entire electron kinetic energy region and exhibits very flat energy dependence in
the 10-100 eV region.
PMID- 25122238
TI - Order parameter for structural heterogeneity in disordered solids.
AB - We construct a structural order parameter from the energy equipartition of normal
modes of vibration to quantify the structural heterogeneity in disordered solids.
The order parameter exhibits strong spatial correlations with low-temperature
dynamics and local structural entropy. To characterize the role of particles with
the most defective local structures identified by the order parameter, we pin
them and measure the system response. It turns out that particles with the
largest value of the order parameter are responsible for the quasilocalized low
frequency vibration, instability, softening, and nonaffinity of disordered
solids. The order parameter thus crucially links the heterogeneous structure to
low-temperature dynamics and mechanical properties of disordered solids.
PMID- 25122240
TI - Front propagation in cellular flows for fast reaction and small diffusivity.
AB - We investigate the influence of fluid flows on the propagation of chemical fronts
arising in Fisher-Kolmogorov-Petrovsky-Piskunov (FKPP) type models. We develop an
asymptotic theory for the front speed in a cellular flow in the limit of small
molecular diffusivity and fast reaction, i.e., large Peclet (Pe) and Damkohler
(Da) numbers. The front speed is expressed in terms of a periodic path--an
instanton--that minimizes a certain functional. This leads to an efficient
procedure to calculate the front speed, and to closed-form expressions for
(logPe)(-1) ? Da ? Pe and for Da ? Pe. Our theoretical predictions are compared
with (i) numerical solutions of an eigenvalue problem and (ii) simulations of the
advection-diffusion-reaction equation.
PMID- 25122241
TI - Dynamics of strongly correlated and strongly inhomogeneous plasmas.
AB - Kinetic and fluid equations are derived for the dynamics of classical
inhomogeneous trapped plasmas in the strong coupling regime. The starting point
is an extended Singwi-Tosi-Land-Sjolander (STLS) ansatz for the dynamic
correlation function, which is allowed to depend on time and both particle
coordinates separately. The time evolution of the correlation function is
determined from the second equation of the Bogolyubov-Born-Green-Kirkwood-Yvon
hierarchy. We study the equations in the linear limit and derive a nonlocal
equation for the fluid displacement field. Comparisons to first-principles
molecular dynamics simulations reveal an excellent quality of our approach
thereby overcoming the limitations of the broadly used STLS scheme.
PMID- 25122243
TI - Generalized Klein-Gordon models: behavior around the ground state condensate.
AB - In this work, we investigate the balance between the nonlinear and linear
interaction energy of an interparticle anharmonic system in the vicinity of the
ground state condensate. As a result, we find that the nonlinear interaction
energy is very significant in the vicinity of each degree of freedom. We address
some potential applications of the findings to miscellaneous areas of interests
such as soliton theory, hydrodynamics, solid state physics, ferromagnetic and
ferroelectric domain walls, condensed matter physics, and particle physics, among
others.
PMID- 25122244
TI - Estimation of probability densities using scale-free field theories.
AB - The question of how best to estimate a continuous probability density from finite
data is an intriguing open problem at the interface of statistics and physics.
Previous work has argued that this problem can be addressed in a natural way
using methods from statistical field theory. Here I describe results that allow
this field-theoretic approach to be rapidly and deterministically computed in low
dimensions, making it practical for use in day-to-day data analysis. Importantly,
this approach does not impose a privileged length scale for smoothness of the
inferred probability density, but rather learns a natural length scale from the
data due to the tradeoff between goodness of fit and an Occam factor. Open source
software implementing this method in one and two dimensions is provided.
PMID- 25122242
TI - Reduced instability growth with high-adiabat high-foot implosions at the National
Ignition Facility.
AB - Hydrodynamic instabilities are a major obstacle in the quest to achieve ignition
as they cause preexisting capsule defects to grow and ultimately quench the
fusion burn in experiments at the National Ignition Facility. Unstable growth at
the ablation front has been dramatically reduced in implosions with "high-foot"
drives as measured using x-ray radiography of modulations at the most dangerous
wavelengths (Legendre mode numbers of 30-90). These growth reductions have helped
to improve the performance of layered DT implosions reported by O. A. Hurricane
et al. [Nature (London) 506, 343 (2014)], when compared to previous "low-foot"
experiments, demonstrating the value of stabilizing ablation-front growth and
providing directions for future ignition designs.
PMID- 25122245
TI - Depinning of stiff directed lines in random media.
AB - Driven elastic manifolds in random media exhibit a depinning transition to a
state with nonvanishing velocity at a critical driving force. We study the
depinning of stiff directed lines, which are governed by a bending rigidity
rather than line tension. Their equation of motion is the (quenched) Herring
Mullins equation, which also describes surface growth governed by surface
diffusion. Stiff directed lines are particularly interesting as there is a
localization transition in the static problem at a finite temperature and the
commonly exploited time ordering of states by means of Middleton's theorems
[Phys. Rev. Lett. 68, 670 (1992)] is not applicable. We employ analytical
arguments and numerical simulations to determine the critical exponents and
compare our findings with previous works and functional renormalization group
results, which we extend to the different line elasticity. We see evidence for
two distinct correlation length exponents.
PMID- 25122246
TI - Fisher exponent from pseudo-epsilon expansion.
AB - The critical exponent eta for three-dimensional systems with an n-vector order
parameter is evaluated in the framework of the pseudo-epsilon expansion approach.
The pseudo-epsilon expansion (tau series) for eta found up to the tau(7) term for
n = 0, 1, 2, 3 and within the tau(6) order for general n is shown to have a
structure that is rather favorable for getting numerical estimates. The use of
Pade approximants and direct summation of the tau series result in iteration
procedures rapidly converging to the asymptotic values that are very close to the
most reliable numerical estimates of eta known today. The origin of such an
efficiency is discussed and shown to lie in the general properties of the pseudo
epsilon expansion machinery interfering with some peculiarities of the
renormalization group expansion of eta.
PMID- 25122247
TI - Anomalous diffusion induced by enhancement of memory.
AB - We introduced simple microscopic non-Markovian walk models which describe the
underlying mechanism of anomalous diffusions. In the models, we considered the
competitions between randomness and memory effects of previous history by
introducing the probability parameters. The memory effects were considered in two
aspects: one is the perfect memory of whole history and the other is the latest
memory enhanced with time. In the perfect memory model superdiffusion was induced
with the relation of the Hurst exponent H to the controlling parameter p as H = p
for p>1/2, while in the latest memory enhancement models, anomalous diffusions
involving both superdiffusion and subdiffusion were induced with the relations H
= (1+alpha)/2 and H = (1-alpha)/2 for 0 <= alpha <= 1, where alpha is the
parameter controlling the degree of the latest memory enhancement. Also we found
that, although the latest memory was only considered, the memory improved with
time results in the long-range correlations between steps and the correlations
increase as time goes on. Thus we suggest the memory enhancement as a key origin
describing anomalous diffusions.
PMID- 25122249
TI - Topological phase transition in a discrete quasicrystal.
AB - We investigate a two-dimensional tiling model. Even though the degrees of freedom
in this model are discrete, it has a hidden continuous global symmetry in the
infinite lattice limit, whose corresponding Goldstone modes are the
quasicrystalline phasonic degrees of freedom. We show that due to this continuous
symmetry and despite the apparent discrete nature of the model, a topological
phase transition from a quasi-long-range ordered to a disordered phase occurs at
a finite temperature, driven by vortex proliferation. We argue that some of the
results are universal properties of two-dimensional systems whose ground state is
a quasicrystalline state.
PMID- 25122248
TI - Nonsteady dynamic properties of a domain wall for the creep state under an
alternating driving field.
AB - With Monte Carlo simulations, the nonsteady dynamic properties of a domain wall
have been systematically investigated for the thermally activated creep state
under an alternating driving field. Taking the driven random-field Ising model in
two dimensions as an example, two distinct growth stages of the domain interface
are identified with both the correlation length and roughness function. One stage
belongs to the universality class of the random depositions, and the other to
that of the quenched Edwards-Wilkinson equation. In the latter case, due to the
dynamic effect of overhangs, the domain interface may exhibit an intrinsic
anomalous scaling behavior, different from that of the quenched Edwards-Wilkinson
equation.
PMID- 25122250
TI - Thermodynamic properties and entropy scaling law for diffusivity in soft spheres.
AB - The purely repulsive soft-sphere system, where the interaction potential is
inversely proportional to the pair separation raised to the power n, is
considered. The Laplace transform technique is used to derive its thermodynamic
properties in terms of the potential energy and its density derivative obtained
from molecular dynamics simulations. The derived expressions provide an analytic
framework with which to explore soft-sphere thermodynamics across the whole
softness-density fluid domain. The trends in the isochoric and isobaric heat
capacity, thermal expansion coefficient, isothermal and adiabatic bulk moduli,
Gruneisen parameter, isothermal pressure, and the Joule-Thomson coefficient as a
function of fluid density and potential softness are described using these
formulas supplemented by the simulation-derived equation of state. At low
densities a minimum in the isobaric heat capacity with density is found, which is
a new feature for a purely repulsive pair interaction. The hard-sphere and n = 3
limits are obtained, and the low density limit specified analytically for any n
is discussed. The softness dependence of calculated quantities indicates freezing
criteria based on features of the radial distribution function or derived
functions of it are not expected to be universal. A new and accurate formula
linking the self-diffusion coefficient to the excess entropy for the entire fluid
softness-density domain is proposed, which incorporates the kinetic theory
solution for the low density limit and an entropy-dependent function in an
exponential form. The thermodynamic properties (or their derivatives), structural
quantities, and diffusion coefficient indicate that three regions specified by a
convex, concave, and intermediate density dependence can be expected as a
function of n, with a narrow transition region within the range 5 < n < 8.
PMID- 25122251
TI - Nonequilibrium ensemble inequivalence and large deviations of the density in the
ABC model.
AB - We consider the one-dimensional driven ABC model under particle-conserving and
particle-nonconserving processes. Two limiting cases are studied: (a) The rates
of the nonconserving processes are vanishingly slow compared with the conserving
processes in the thermodynamic limit and (b) the two rates are comparable. For
case (a) we provide a detailed analysis of the phase diagram and the large
deviations function of the overall density, G(r). The phase diagram of the
nonconserving model, derived from G(r), is found to be different from the
conserving one. This difference, which stems from the nonconvexity of G(r), is
analogous to ensemble inequivalence found in equilibrium systems with long-range
interactions. An outline of the analysis of case (a) was given in an earlier
letter. For case (b) we show that, unlike the conserving model, the nonconserving
model exhibits a moving density profile in the steady state with a velocity that
remains finite in the thermodynamic limit. Moreover, in contrast with case (a),
the critical lines of the conserving and nonconserving models do not coincide.
These are new features which are present only when the rates of the conserving
and nonconserving processes are comparable. In addition, we analyze G(r) in case
(b) using macroscopic fluctuations theory. Much of the derivation presented in
this paper is applicable to any driven-diffusive system coupled to an external
particle bath via a slow dynamics.
PMID- 25122253
TI - Long-range correlations in a locally driven exclusion process.
AB - We show that the presence of a driven bond in an otherwise diffusive lattice gas
with simple exclusion interaction results in long-range density-density
correlation in its stationary state. In dimensions d > 1 we show that in the
thermodynamic limit this correlation decays as C(r,s)~(r(2)+s(2))(-d) at large
distances r and s away from the drive with |r - s| ? 1. This is derived using an
electrostatic analogy whereby C(r,s) is expressed as the potential due to a
configuration of electrostatic charges distributed in 2d dimension. At bulk
density rho=1/2 we show that the potential is that of a localized quadrupolar
charge. At other densities the same is correct in leading order in the strength
of the drive and it is argued numerically to be valid at higher orders.
PMID- 25122252
TI - Generation of a tunable environment for electrical oscillator systems.
AB - Many physical, chemical, and biological systems can be modeled by means of random
frequency harmonic oscillator systems. Even though the noise-free evolution of
harmonic oscillator systems can be easily implemented, the way to experimentally
introduce, and control, noise effects due to a surrounding environment remains a
subject of lively interest. Here, we experimentally demonstrate a setup that
provides a unique tool to generate a fully tunable environment for classical
electrical oscillator systems. We illustrate the operation of the setup by
implementing the case of a damped random-frequency harmonic oscillator. The high
degree of tunability and control of our scheme is demonstrated by gradually
modifying the statistics of the oscillator's frequency fluctuations. This tunable
system can readily be used to experimentally study interesting noise effects,
such as noise-induced transitions in systems driven by multiplicative noise, and
noise-induced transport, a phenomenon that takes place in quantum and classical
coupled oscillator networks.
PMID- 25122254
TI - Equilibrium states of generic quantum systems subject to periodic driving.
AB - When a closed quantum system is driven periodically with period T, it approaches
a periodic state synchronized with the drive in which any local observable
measured stroboscopically approaches a steady value. For integrable systems, the
resulting behavior is captured by a periodic version of a generalized Gibbs
ensemble. By contrast, here we show that for generic nonintegrable interacting
systems, local observables become independent of the initial state entirely.
Essentially, this happens because Floquet eigenstates of the driven system at
quasienergy omega(alpha) consist of a mixture of the exponentially many
eigenstates of the undriven Hamiltonian, which are thus drawn from the entire
extensive undriven spectrum. This is a form of equilibration which depends only
on the Hilbert space of the undriven system and not on any details of its
Hamiltonian.
PMID- 25122255
TI - Self-propelled particle in an external potential: existence of an effective
temperature.
AB - We study a stationary state of a single self-propelled, athermal particle in
linear and quadratic external potentials. The self-propulsion is modeled as a
fluctuating internal driving force evolving according to the Ornstein-Uhlenbeck
process, independently of the state of the particle. Without an external
potential, in the long time limit, the self-propelled particle moving in a
viscous medium performs diffusive motion, which allows one to identify an
effective temperature. We show that in the presence of a linear external
potential the stationary state distribution has an exponential form with the
sedimentation length determined by the effective temperature of the free self
propelled particle. In the presence of a quadratic external potential the
stationary state distribution has a Gaussian form. However, in general, this
distribution is not determined by the effective temperature of the free self
propelled particle.
PMID- 25122256
TI - Small-cluster renormalization group in Ising and Blume-Emery-Griffiths models
with ferromagnetic, antiferromagnetic, and quenched disordered magnetic
interactions.
AB - The Ising and Blume-Emery-Griffiths (BEG) models' critical behavior is analyzed
in two dimensions and three dimensions by means of a renormalization group scheme
on small clusters made of a few lattice cells. Different kinds of cells are
proposed for both ordered and disordered model cases. In particular, cells
preserving a possible antiferromagnetic ordering under renormalization allow for
the determination of the Neel critical point and its scaling indices. These also
provide more reliable estimates of the Curie fixed point than those obtained
using cells preserving only the ferromagnetic ordering. In all studied
dimensions, the present procedure does not yield a strong-disorder critical point
corresponding to the transition to the spin-glass phase. This limitation is
thoroughly analyzed and motivated.
PMID- 25122257
TI - Revisiting Feynman's ratchet with thermoelectric transport theory.
AB - We show how the formalism used for thermoelectric transport may be adapted to
Smoluchowski's seminal thought experiment, also known as Feynman's ratchet and
pawl system. Our analysis rests on the notion of useful flux, which for a
thermoelectric system is the electrical current and for Feynman's ratchet is the
effective jump frequency. Our approach yields original insight into the
derivation and analysis of the system's properties. In particular we define an
entropy per tooth in analogy with the entropy per carrier or Seebeck coefficient,
and we derive the analog to Kelvin's second relation for Feynman's ratchet. Owing
to the formal similarity between the heat fluxes balance equations for a
thermoelectric generator (TEG) and those for Feynman's ratchet, we introduce a
distribution parameter gamma that quantifies the amount of heat that flows
through the cold and hot sides of both heat engines. While it is well established
that gamma = 1/2 for a TEG, it is equal to 1 for Feynman's ratchet. This implies
that no heat may be rejected in the cold reservoir for the latter case. Further,
the analysis of the efficiency at maximum power shows that the so-called Feynman
efficiency corresponds to that of an exoreversible engine, with gamma = 1. Then,
turning to the nonlinear regime, we generalize the approach based on the
convection picture and introduce two different types of resistance to distinguish
the dynamical behavior of the considered system from its ability to dissipate
energy. We finally put forth the strong similarity between the original Feynman
ratchet and a mesoscopic thermoelectric generator with a single conducting
channel.
PMID- 25122258
TI - Effect of coupling strength on a two-lane partially asymmetric coupled totally
asymmetric simple exclusion process with Langmuir kinetics.
AB - We analyze an open system comprised of two parallel totally asymmetric simple
exclusion processes with particle attachment and detachment in the bulk under
partially asymmetric coupling conditions. The phase diagrams are obtained using
boundary layer analysis of continuum mean-field equations and characterized for
different values of lane-changing rates. The structure of the phase diagram
remains qualitatively the same as the one in fully asymmetric coupling conditions
up to a certain critical order of lane-changing rates, after which significant
changes are found in the phase diagram. The effect of system size on the steady
state dynamics has also been examined. To validate theoretical findings,
extensive Monte Carlo simulations are carried out.
PMID- 25122259
TI - Energy pumping in electrical circuits under avalanche noise.
AB - We theoretically study energy pumping processes in an electrical circuit with
avalanche diodes, where non-Gaussian athermal noise plays a crucial role. We show
that a positive amount of energy (work) can be extracted by an external
manipulation of the circuit in a cyclic way, even when the system is spatially
symmetric. We discuss the properties of the energy pumping process for both
quasistatic and finite-time cases, and analytically obtain formulas for the
amounts of the work and the power. Our results demonstrate the significance of
the non-Gaussianity in energetics of electrical circuits.
PMID- 25122260
TI - Role of the interpretation of stochastic calculus in systems with cross
correlated Gaussian white noises.
AB - We derive the Fokker-Planck equation for multivariable Langevin equations with
cross-correlated Gaussian white noises for an arbitrary interpretation of the
stochastic differential equation. We formulate the conditions when the solution
of the Fokker-Planck equation does not depend on which stochastic calculus is
adopted. Further, we derive an equivalent multivariable Ito stochastic
differential equation for each possible interpretation of the multivariable
Langevin equation. To demonstrate the usefulness and significance of these
general results, we consider the motion of Brownian particles. We study in detail
the stability conditions for harmonic oscillators with two white noises, one of
which is additive, random forcing, and the other, which accounts for fluctuations
of either the damping or the spring coefficient, is multiplicative. We analyze
the role of cross correlation in terms of the different noise interpretations and
confirm the theoretical predictions via numerical simulations. We stress the
interest of our results for numerical simulations of stochastic differential
equations with an arbitrary interpretation of the stochastic integrals.
PMID- 25122261
TI - Scaling of clusters near discontinuous percolation transitions in hyperbolic
networks.
AB - We investigate the onset of the discontinuous percolation transition in small
world hyperbolic networks by studying the systems-size scaling of the typical
largest cluster approaching the transition, p ? p(c). To this end, we determine
the average size of the largest cluster ~ N(Psi(p)) in the thermodynamic
limit using real-space renormalization of cluster-generating functions for bond
and site percolation in several models of hyperbolic networks that provide exact
results. We determine that all our models conform to the recently predicted
behavior regarding the growth of the largest cluster, which found diverging,
albeit subextensive, clusters spanning the system with finite probability well
below p(c) and at most quadratic corrections to unity in Psi(p) for p ? p(c). Our
study suggests a large universality in the cluster formation on small-world
hyperbolic networks and the potential for an alternative mechanism in the cluster
formation dynamics at the onset of discontinuous percolation transitions.
PMID- 25122262
TI - Scaling hypothesis for the Euclidean bipartite matching problem.
AB - We propose a simple yet very predictive form, based on a Poisson's equation, for
the functional dependence of the cost from the density of points in the Euclidean
bipartite matching problem. This leads, for quadratic costs, to the analytic
prediction of the large N limit of the average cost in dimension d = 1,2 and of
the subleading correction in higher dimension. A nontrivial scaling exponent,
gamma(d) = d-2/d, which differs from the monopartite's one, is found for the
subleading correction. We argue that the same scaling holds true for a generic
cost exponent in dimension d > 2.
PMID- 25122263
TI - Optimal efficiency of a noisy quantum heat engine.
AB - In this article we use optimal control to maximize the efficiency of a quantum
heat engine executing the Otto cycle in the presence of external noise. We
optimize the engine performance for both amplitude and phase noise. In the case
of phase damping we additionally show that the ideal performance of a noiseless
engine can be retrieved in the adiabatic (long time) limit. The results obtained
here are useful in the quest for absolute zero, the design of quantum
refrigerators that can cool a physical system to the lowest possible temperature.
They can also be applied to the optimal control of a collection of classical
harmonic oscillators sharing the same time-dependent frequency and subjected to
similar noise mechanisms. Finally, our methodology can be used for the
optimization of other interesting thermodynamic processes.
PMID- 25122264
TI - Multiple phase transitions in extended hard-core lattice gas models in two
dimensions.
AB - We study the k-NN hard-core lattice gas model in which the first k next-nearest
neighbor sites of a particle are excluded from occupation by other particles on a
two-dimensional square lattice. This model is the lattice version of the hard
disk system with increasing k corresponding to decreasing lattice spacing. While
the hard-disk system is known to undergo a two-step freezing process with
increasing density, the lattice model has been known to show only one transition.
Here, based on Monte Carlo simulations and high-density expansions of the free
energy and density, we argue that for k = 4,10,11,14,?, the lattice model
undergoes multiple transitions with increasing density. Using Monte Carlo
simulations, we confirm the same for k = 4,...,11. This, in turn, resolves an
existing puzzle as to why the 4-NN model has a continuous transition against the
expectation of a first-order transition.
PMID- 25122265
TI - Quantum systems equilibrate rapidly for most observables.
AB - Considering any Hamiltonian, any initial state, and measurements with a small
number of possible outcomes compared to the dimension, we show that most
measurements are already equilibrated. To investigate nontrivial equilibration,
we therefore consider a restricted set of measurements. When the initial state is
spread over many energy levels, and we consider the set of observables for which
this state is an eigenstate, most observables are initially out of equilibrium
yet equilibrate rapidly. Moreover, all two-outcome measurements, where one of the
projectors is of low rank, equilibrate rapidly.
PMID- 25122266
TI - Mean-field universality class induced by weak hyperbolic curvatures.
AB - Order-disorder phase transition of the ferromagnetic Ising model is investigated
on a series of two-dimensional lattices that have negative Gaussian curvatures.
Exceptional lattice sites of coordination number seven are distributed on the
triangular lattice, where the typical distance between the nearest exceptional
sites is proportional to an integer parameter n. Thus, the corresponding
curvature is asymptotically proportional to -n(-2). Spontaneous magnetization and
specific heat are calculated by means of the corner transfer matrix
renormalization group method. For all the finite n cases, we observe the mean
field-like phase transition. It is confirmed that the entanglement entropy at the
transition temperature is linear in (c/6)ln n, where c = 1/2 is the central
charge of the Ising model. The fact agrees with the presence of the typical
length scale n being proportional to the curvature radius.
PMID- 25122267
TI - Fluctuations of isolated and confined surface steps of monatomic height.
AB - The temporal evolution of equilibrium fluctuations for surface steps of monatomic
height is analyzed studying one-dimensional solid-on-solid models. Using Monte
Carlo simulations, fluctuations due to periphery diffusion (PD) as well as due to
evaporation and condensation are considered, both for isolated steps and for
steps confined by the presence of straight steps. For isolated steps, the
dependence of the characteristic power laws, their exponents, and prefactors on
temperature, slope, and curvature is elucidated, with the main emphasis on PD,
taking into account finite-size effects. The entropic repulsion due to a second
straight step may lead, among other things, to an interesting transient power-law
like growth of the fluctuations, for PD. Findings are compared to results of
previous Monte Carlo simulations and predictions based, mostly, on scaling
arguments and Langevin theory.
PMID- 25122268
TI - Numerical test of hydrodynamic fluctuation theory in the Fermi-Pasta-Ulam chain.
AB - Recent work has developed a nonlinear hydrodynamic fluctuation theory for a chain
of coupled anharmonic oscillators governing the conserved fields, namely,
stretch, momentum, and energy. The linear theory yields two propagating sound
modes and one diffusing heat mode, all three with diffusive broadening. In
contrast, the nonlinear theory predicts that, at long times, the sound mode
correlations satisfy Kardar-Parisi-Zhang scaling, while the heat mode
correlations have Levy-walk scaling. In the present contribution we report on
molecular dynamics simulations of Fermi-Pasta-Ulam chains to compute various
spatiotemporal correlation functions and compare them with the predictions of the
theory. We obtain very good agreement in many cases, but also some deviations.
PMID- 25122269
TI - Reinterpretation of velocity-dependent atomic friction: influence of the inherent
instrumental noise in friction force microscopes.
AB - We have applied both the master equation method and harmonic transition state
theory to interpret the velocity-dependent friction behavior observed in atomic
friction experiments. To understand the discrepancy between attempt frequencies
measured in atomic force microscopy experiments and those estimated by
theoretical models, both thermal noise and instrumental noise are introduced into
the model. It is found that the experimentally observed low attempt frequency and
the transition point at low velocity regimes can be interpreted in terms of the
instrumental noise inherent in atomic force microscopy. In contrast to previous
models, this model also predicts (1) the existence of a two-slope curve of
velocity dependence and (2) the decrease of critical velocity with temperature,
which provides clues for further experimental verification of the influence of
instrumental noise in friction measurements.
PMID- 25122270
TI - Code-division multiple-access multiuser demodulator by using quantum
fluctuations.
AB - We examine the average-case performance of a code-division multiple-access (CDMA)
multiuser demodulator in which quantum fluctuations are utilized to demodulate
the original message within the context of Bayesian inference. The quantum
fluctuations are built into the system as a transverse field in the infinite
range Ising spin glass model. We evaluate the performance measurements by using
statistical mechanics. We confirm that the CDMA multiuser modulator using quantum
fluctuations achieve roughly the same performance as the conventional CDMA
multiuser modulator through thermal fluctuations on average. We also find that
the relationship between the quality of the original information retrieval and
the amplitude of the transverse field is somehow a "universal feature" in typical
probabilistic information processing, viz., in image restoration, error
correcting codes, and CDMA multiuser demodulation.
PMID- 25122271
TI - Strong local passivity in finite quantum systems.
AB - Passive states of quantum systems are states from which no system energy can be
extracted by any cyclic (unitary) process. Gibbs states of all temperatures are
passive. Strong local (SL) passive states are defined to allow any general
quantum operation, but the operation is required to be local, being applied only
to a specific subsystem. Any mixture of eigenstates in a system-dependent
neighborhood of a nondegenerate entangled ground state is found to be SL passive.
In particular, Gibbs states are SL passive with respect to a subsystem only at or
below a critical system-dependent temperature. SL passivity is associated in many
body systems with the presence of ground state entanglement in a way suggestive
of collective quantum phenomena such as quantum phase transitions,
superconductivity, and the quantum Hall effect. The presence of SL passivity is
detailed for some simple spin systems where it is found that SL passivity is
neither confined to systems of only a few particles nor limited to the near
vicinity of the ground state.
PMID- 25122272
TI - Logarithmic finite-size effects on interfacial free energies: phenomenological
theory and Monte Carlo studies.
AB - The computation of interfacial free energies between coexisting phases (e.g.,
saturated vapor and liquid) by computer simulation methods is still a challenging
problem due to the difficulty of an atomistic identification of an interface and
interfacial fluctuations on all length scales. The approach to estimate the
interfacial tension from the free-energy excess of a system with interfaces
relative to corresponding single-phase systems does not suffer from the first
problem but still suffers from the latter. Considering d-dimensional systems with
interfacial area L(d-1) and linear dimension L(z) in the direction perpendicular
to the interface, it is argued that the interfacial fluctuations cause
logarithmic finite-size effects of order ln(L)/L(d-1) and order ln(L(z))/L(d-1),
in addition to regular corrections (with leading-order const/L(d-1)). A
phenomenological theory predicts that the prefactors of the logarithmic terms are
universal (but depend on the applied boundary conditions and the considered
statistical ensemble). The physical origin of these corrections are the
translational entropy of the interface as a whole, "domain breathing" (coupling
of interfacial fluctuations to the bulk order parameter fluctuations of the
coexisting domains), and capillary waves. Using a new variant of the ensemble
switch method, interfacial tensions are found from Monte Carlo simulations of d =
2 and d = 3 Ising models and a Lennard-Jones fluid. The simulation results are
fully consistent with the theoretical predictions.
PMID- 25122273
TI - Dynamic hysteretic features of Ising-type thin films.
AB - In order to elucidate the nature of hysteresis characteristics in a magnetic
Ising-type thin film with a certain thickness, such as types of frequency
dispersion curves, decay of hysteresis loop area, corresponding coercive field
and remanent magnetization values, etc., we investigate the hysteretic response
of each layer within effective-field theory. Throughout the analysis, the best
appropriate parameter values are chosen since they would allow us to observe the
reversed magnetic hysteresis after a certain value of external field frequency.
This eccentric phenomenon has prompted us to associate it to the domain
nucleation and growth mechanism in the dynamic process. Exotic shapes of the
response for different layer indices in two different regimes of modified surface
exchange are particularly emphasized.
PMID- 25122274
TI - Two-point resistance of a resistor network embedded on a globe.
AB - We consider the problem of two-point resistance in an (m-1) * n resistor network
embedded on a globe, a geometry topologically equivalent to an m * n cobweb with
its boundary collapsed into one single point. We deduce a concise formula for the
resistance between any two nodes on the globe using a method of direct summation
pioneered by one of us [Z.-Z. Tan, L. Zhou, and J. H. Yang, J. Phys. A: Math.
Theor. 46, 195202 (2013)]. This method is contrasted with the Laplacian matrix
approach formulated also by one of us [F. Y. Wu, J. Phys. A: Math. Gen. 37, 6653
(2004)], which is difficult to apply to the geometry of a globe. Our analysis
gives the result in the form of a single summation.
PMID- 25122275
TI - Effects of cross-correlated noises on the transport of active Brownian particles.
AB - The transport properties of active Brownian particles driven by cross-correlated
noises are investigated. Using the Langevin and Fokker-Planck approaches, the
theoretical analysis of the model is presented. It is found that correlated
noises can produce a net velocity, which stems from the symmetric breaking of the
system induced by the correlation between noises. The mean velocity is negative
for positive correlation but positive for negative correlation. The mean velocity
increases while the effective diffusion decreases as the absolute value of the
correlation between the noises increases. Both the mean velocity and the
effective diffusion show a nonmonotonic dependence on the multiplicative noise,
but a monotonically decreasing dependence on the additive noise.
PMID- 25122276
TI - Large pseudocounts and L2-norm penalties are necessary for the mean-field
inference of Ising and Potts models.
AB - The mean-field (MF) approximation offers a simple, fast way to infer direct
interactions between elements in a network of correlated variables, a common,
computationally challenging problem with practical applications in fields ranging
from physics and biology to the social sciences. However, MF methods achieve
their best performance with strong regularization, well beyond Bayesian
expectations, an empirical fact that is poorly understood. In this work, we study
the influence of pseudocount and L(2)-norm regularization schemes on the quality
of inferred Ising or Potts interaction networks from correlation data within the
MF approximation. We argue, based on the analysis of small systems, that the
optimal value of the regularization strength remains finite even if the sampling
noise tends to zero, in order to correct for systematic biases introduced by the
MF approximation. Our claim is corroborated by extensive numerical studies of
diverse model systems and by the analytical study of the m-component spin model
for large but finite m. Additionally, we find that pseudocount regularization is
robust against sampling noise and often outperforms L(2)-norm regularization,
particularly when the underlying network of interactions is strongly
heterogeneous. Much better performances are generally obtained for the Ising
model than for the Potts model, for which only couplings incoming onto medium
frequency symbols are reliably inferred.
PMID- 25122277
TI - Exclusion processes with avalanches.
AB - In an exclusion process with avalanches, when a particle hops to a neighboring
empty site which is adjacent to an island the particle on the other end of the
island immediately hops, and if it joins another island this triggers another
hop. There are no restrictions on the length of the islands and the duration of
the avalanche. This process is well defined in the low-density region rho < 1/2.
We describe the nature of steady states (on a ring) and determine all correlation
functions. For the asymmetric version of the process, we compute the steady state
current, and we describe shock and rarefaction waves which arise in the evolution
of the step-function initial profile. For the symmetric version, we determine the
diffusion coefficient and examine the evolution of a tagged particle.
PMID- 25122278
TI - Nonergodicity, fluctuations, and criticality in heterogeneous diffusion
processes.
AB - We study the stochastic behavior of heterogeneous diffusion processes with the
power-law dependence D(x) ~ |x|(alpha) of the generalized diffusion coefficient
encompassing sub- and superdiffusive anomalous diffusion. Based on statistical
measures such as the amplitude scatter of the time-averaged mean-squared
displacement of individual realizations, the ergodicity breaking and non
Gaussianity parameters, as well as the probability density function P(x,t), we
analyze the weakly nonergodic character of the heterogeneous diffusion process
and, particularly, the degree of irreproducibility of individual realizations. As
we show, the fluctuations between individual realizations increase with growing
modulus |alpha| of the scaling exponent. The fluctuations appear to diverge when
the critical value alpha = 2 is approached, while for even larger alpha the
fluctuations decrease, again. At criticality, the power-law behavior of the mean
squared displacement changes to an exponentially fast growth, and the
fluctuations of the time-averaged mean-squared displacement do not converge for
increasing number of realizations. From a systematic comparison we observe some
striking similarities of the heterogeneous diffusion process with the familiar
subdiffusive continuous time random walk process with power-law waiting time
distribution and diverging characteristic waiting time.
PMID- 25122279
TI - Kinetic Monte Carlo simulations of proton conductivity.
AB - The kinetic Monte Carlo method is used to model the dynamic properties of proton
diffusion in anhydrous proton conductors. The results have been discussed with
reference to a two-step process called the Grotthuss mechanism. There is a
widespread belief that this mechanism is responsible for fast proton mobility. We
showed in detail that the relative frequency of reorientation and diffusion
processes is crucial for the conductivity. Moreover, the current dependence on
proton concentration has been analyzed. In order to test our microscopic model
the proton transport in polymer electrolyte membranes based on benzimidazole
C(7)H(6)N(2) molecules is studied.
PMID- 25122280
TI - Emergence of limit-periodic order in tiling models.
AB - A two-dimensional (2D) lattice model defined on a triangular lattice with nearest
and next-nearest-neighbor interactions based on the Taylor-Socolar monotile is
known to have a limit-periodic ground state. The system reaches that state during
a slow quench through an infinite sequence of phase transitions. We study the
model as a function of the strength of the next-nearest-neighbor interactions and
introduce closely related 3D models with only nearest-neighbor interactions that
exhibit limit-periodic phases. For models with no next-nearest-neighbor
interactions of the Taylor-Socolar type, there is a large degenerate class of
ground states, including crystalline patterns and limit-periodic ones, but a slow
quench still yields the limit-periodic state. For the Taylor-Socolar lattic
model, we present calculations of the diffraction pattern for a particular
decoration of the tile that permits exact expressions for the amplitudes and
identify domain walls that slow the relaxation times in the ordered phases. For
one of the 3D models, we show that the phase transitions are first order, with
equilibrium structures that can be more complex than in the 2D case, and we
include a proof of aperiodicity for a geometrically simple tile with only nearest
neighbor matching rules.
PMID- 25122281
TI - Nonequilibrium dynamics of four-point correlations of collective density
fluctuations in a supercooled liquid.
AB - In this paper we study the four-point correlation function chi(4) of collective
density fluctuations in a nonequilibrium liquid. The equilibration is controlled
by a modified stretched exponential behavior (exp[-(t(w)/tau)(beta)]) having the
relaxation time tau dependent on the aging time t(w). Similar aging behavior has
been seen experimentally in supercooled liquids. The basic equations of
fluctuating nonlinear hydrodynamics are solved here numerically to obtain chi(4)
for equilibrium and non equilibrium states. We also identify a dynamic length
scale xi from the equilibrated function. xi(T) grows with fall of temperature T.
From a broader perspective, we demonstrate here that the characteristic
signatures of dynamical heterogeneities in a supercooled liquid, observed
previously in computer simulations of the dynamics of a small number of
particles, are also present in the coarse grained equations of generalized
hydrodynamics.
PMID- 25122282
TI - Critical Casimir interactions between spherical particles in the presence of bulk
ordering fields.
AB - The spatial suppression of order parameter fluctuations in a critical media
produces critical Casimir forces acting on confining surfaces. This scenario is
realized in a critical binary mixture near the demixing transition point that
corresponds to the second-order phase transition of the Ising universality class.
Due to these critical interactions similar colloids, immersed in a critical
binary mixture near the consolute point, exhibit attraction. The numerical method
for computation of the interaction potential between two spherical particles
using Monte Carlo simulations for the Ising model is proposed. This method is
based on the integration of the local magnetization over the applied local
magnetic field. For the stronger interaction the concentration of the component
of the mixture that does not wet colloidal particles should be larger than the
critical concentration. The strongest amplitude of the interactions is observed
below the critical point.
PMID- 25122283
TI - Rare regions and Griffiths singularities at a clean critical point: the five
dimensional disordered contact process.
AB - We investigate the nonequilibrium phase transition of the disordered contact
process in five space dimensions by means of optimal fluctuation theory and Monte
Carlo simulations. We find that the critical behavior is of mean-field type,
i.e., identical to that of the clean five-dimensional contact process. It is
accompanied by off-critical power-law Griffiths singularities whose dynamical
exponent z' saturates at a finite value as the transition is approached. These
findings resolve the apparent contradiction between the Harris criterion, which
implies that weak disorder is renormalization-group irrelevant, and the rare
region classification, which predicts unconventional behavior. We confirm and
illustrate our theory by large-scale Monte Carlo simulations of systems with up
to 70(5) sites. We also relate our results to a recently established general
relation between the Harris criterion and Griffiths singularities [Phys. Rev.
Lett. 112, 075702 (2014)], and we discuss implications for other phase
transitions.
PMID- 25122284
TI - One-dimensional disordered Ising models by replica and cavity methods.
AB - Using a formalism based on the spectral decomposition of the replicated transfer
matrix for disordered Ising models, we obtain several results that apply both to
isolated one-dimensional systems and to locally treelike graph and factor graph
(p-spin) ensembles. We present exact analytical expressions, which can be
efficiently approximated numerically for many types of correlation functions and
for the average free energies of open and closed finite chains. All the results
achieved, with the exception of those involving closed chains, are then
rigorously derived without replicas, using a probabilistic approach with the same
flavor of cavity method.
PMID- 25122285
TI - Structure and thermodynamic properties of relativistic electron gases.
AB - Relativistic effect is important in many quantum systems but theoretically
complicated from both fundamental and practical perspectives. Herein we introduce
an efficient computational procedure to predict the structure and energetic
properties of relativistic quantum systems by mapping the Pauli principle into an
effective pairwise-additive potential such that the properties of relativistic
nonquantum systems can be readily predicted from conventional liquid-state
methods. We applied our theoretical procedure to relativistic uniform electron
gases and compared the pair correlation functions with those for systems of
nonrelativistic electrons. A simple analytical expression has been developed to
correlate the exchange-correlation free energy of relativistic uniform electron
systems.
PMID- 25122286
TI - 1/ f noise from the laws of thermodynamics for finite-size fluctuations.
AB - Computer simulations of the Ising model exhibit white noise if thermal
fluctuations are governed by Boltzmann's factor alone; whereas we find that the
same model exhibits 1/f noise if Boltzmann's factor is extended to include local
alignment entropy to all orders. We show that this nonlinear correction maintains
maximum entropy during equilibrium fluctuations. Indeed, as with the usual way to
resolve Gibbs' paradox that avoids entropy reduction during reversible processes,
the correction yields the statistics of indistinguishable particles. The
correction also ensures conservation of energy if an instantaneous contribution
from local entropy is included. Thus, a common mechanism for 1/f noise comes from
assuming that finite-size fluctuations strictly obey the laws of thermodynamics,
even in small parts of a large system. Empirical evidence for the model comes
from its ability to match the measured temperature dependence of the spectral
density exponents in several metals and to show non-Gaussian fluctuations
characteristic of nanoscale systems.
PMID- 25122287
TI - Condensation of fluctuations in and out of equilibrium.
AB - Condensation of fluctuations is an interesting phenomenon conceptually distinct
from condensation on average. One striking feature is that, contrary to what
happens on average, condensation of fluctuations may occur even in the absence of
interaction. The explanation emerges from the duality between large deviation
events in the given system and typical events in a new and appropriately biased
system. This phenomenon is investigated in the context of the Gaussian model,
chosen as a paradigmatical noninteracting system, before and after an
instantaneous temperature quench. It is shown that the bias induces a mean-field
like effective interaction responsible for the condensation on average. Phase
diagrams, covering both the equilibrium and the off-equilibrium regimes, are
derived for observables representative of generic behaviors.
PMID- 25122288
TI - Effect of disorder on condensation in the lattice gas model on a random graph.
AB - The lattice gas model of condensation in a heterogeneous pore system, represented
by a random graph of cells, is studied using an exact analytical solution. A
binary mixture of pore cells with different coordination numbers is shown to
exhibit two phase transitions as a function of chemical potential in a certain
temperature range. Heterogeneity in interaction strengths is demonstrated to
reduce the critical temperature and, for large-enough degreeS of disorder,
divides the cells into ones which are either on average occupied or unoccupied.
Despite treating the pore space loops in a simplified manner, the random-graph
model provides a good description of condensation in porous structures containing
loops. This is illustrated by considering capillary condensation in a structural
model of mesoporous silica SBA-15.
PMID- 25122289
TI - Work and efficiency of quantum Otto cycles in power-law trapping potentials.
AB - We study the performance of a quantum Otto cycle operating in trapping potentials
of different shapes. We show that, while both the mean work output and the
efficiency of two Otto cycles in different trapping potentials can be made equal,
the work probability distribution will still be strongly affected by the
difference in structure of the energy levels. To exemplify our results, we study
the family of potentials of the form V(t)(x) ~ x(2q). This family of potentials
possesses a simple scaling property that allows for analytical insights into the
efficiency and work output of the cycle. We perform a comparison of quantum Otto
cycles in various physically relevant scenarios and find that in certain
instances, the efficiency of the cycle is greater when using potentials with
larger values of q, while in other cases, the efficiency is greater with harmonic
traps.
PMID- 25122290
TI - Finite-size corrections to disordered Ising models on random regular graphs.
AB - We derive the analytical expression for the first finite-size correction to the
average free energy of disordered Ising models on random regular graphs. The
formula can be physically interpreted as a weighted sum over all non-self
intersecting loops in the graph, the weight being the free-energy shift due to
the addition of the loop to an infinite tree.
PMID- 25122291
TI - Equilibrium time-correlation functions for one-dimensional hard-point systems.
AB - As recently proposed, the long-time behavior of equilibrium time-correlation
functions for one-dimensional systems are expected to be captured by a nonlinear
extension of fluctuating hydrodynamics. We outline the predictions from the
theory aimed at the comparison with molecular dynamics. We report on numerical
simulations of a fluid with a hard-shoulder potential and of a hard-point gas
with alternating masses. These models have in common that the collision time is
zero and their dynamics amounts to iterating collision by collision. The theory
is well confirmed, with the twist that the nonuniversal coefficients are still
changing at longest accessible times.
PMID- 25122292
TI - Heat transfer in the spin-boson model: a comparative study in the incoherent
tunneling regime.
AB - We study the transfer of heat in the nonequilibrium spin-boson model with an
Ohmic dissipation. In the nonadiabatic limit we derive a formula for the thermal
conductance based on a rate equation formalism at the level of the noninteracting
blip approximation, valid for temperatures T>T(K), with T(K) as the Kondo
temperature. We evaluate this expression analytically assuming either weak or
strong couplings, and demonstrate that our results agree with exact relations.
Far-from-equilibrium situations are further examined, showing a close
correspondence to the linear response limit.
PMID- 25122293
TI - Order-disorder transition in swirled granular disks.
AB - We study the order-disorder transition of horizontally swirled dry and wet
granular disks by means of computer simulations. Our systematic investigation of
the local order formation as a function of amplitude and period of the external
driving force shows that a large cluster of hexagonally ordered particles forms
for both dry and wet granular particles at intermediate driving energies.
Disordered states are found at small and large driving energies. Wet granular
particles reach a higher degree of local hexagonal order with respect to the dry
case. For both cases we report a qualitative phase diagram showing the amount of
local order at different state points. Furthermore, we find that the transition
from hexagonal order to a disordered state is characterized by the appearance of
particles with square local order.
PMID- 25122294
TI - Effect of size polydispersity versus particle shape in dense granular media.
AB - We present a detailed analysis of the morphology of granular systems composed of
frictionless pentagonal particles by varying systematically both the size span
and particle shape irregularity, which represent two polydispersity parameters of
the system. The microstructure is characterized in terms of various statistical
descriptors such as global and local packing fractions, radial distribution
functions, coordination number, and fraction of floating particles. We find that
the packing fraction increases with the two parameters of polydispersity, but the
effect of shape polydispersity for all the investigated structural properties is
significant only at low size polydispersity where the positional and/or
orientational ordering of the particles prevail. We focus in more detail on the
class of side/side contacts, which is the interesting feature of our system as
compared to a packing of disks. We show that the proportion of such contacts has
weak dependence on the polydispersity parameters. The side- side contacts do not
percolate but they define clusters of increasing size as a function of size
polydispersity and decreasing size as a function of shape polydispersity. The
clusters have anisotropic shapes but with a decreasing aspect ratio as
polydispersity increases. This feature is argued to be a consequence of strong
force chains (forces above the mean), which are mainly captured by side-side
contacts. Finally, the force transmission is intrinsically multiscale, with a
mean force increasing linearly with particle size.
PMID- 25122295
TI - Granular flow through an aperture: influence of the packing fraction.
AB - For the last 50 years, the flow of a granular material through an aperture has
been intensely studied in gravity-driven vertical systems (e.g., silos and
hoppers). Nevertheless, in many industrial applications, grains are horizontally
transported at constant velocity, lying on conveyor belts or floating on the
surface of flowing liquids. Unlike fluid flows, that are controlled by the
pressure, granular flow is not sensitive to the local pressure but rather to the
local velocity of the grains at the outlet. We can also expect the flow rate to
depend on the local density of the grains. Indeed, vertical systems are packed in
dense configurations by gravity, but, in contrast, in horizontal systems the
density can take a large range of values, potentially very small, which may
significantly alter the flow rate. In the present article, we study, for
different initial packing fractions, the discharge through an orifice of
monodisperse grains driven at constant velocity by a horizontal conveyor belt. We
report how, during the discharge, the packing fraction is modified by the
presence of the outlet, and we analyze how changes in the packing fraction induce
variations in the flow rate. We observe that variations of packing fraction do
not affect the velocity of the grains at the outlet, and, therefore, we establish
that flow-rate variations are directly related to changes in the packing
fraction.
PMID- 25122296
TI - Memory effect in uniformly heated granular gases.
AB - We evidence a Kovacs-like memory effect in a uniformly driven granular gas. A
system of inelastic hard particles, in the low density limit, can reach a
nonequilibrium steady state when properly forced. By following a certain protocol
for the drive time dependence, we prepare the gas in a state where the granular
temperature coincides with its long time value. The temperature subsequently does
not remain constant but exhibits a nonmonotonic evolution with either a maximum
or a minimum, depending on the dissipation and on the protocol. We present a
theoretical analysis of this memory effect at Boltzmann-Fokker-Planck equation
level and show that when dissipation exceeds a threshold, the response can be
called anomalous. We find excellent agreement between the analytical predictions
and direct Monte Carlo simulations.
PMID- 25122297
TI - Electric double-layer potentials and surface regulation properties measured by
colloidal-probe atomic force microscopy.
AB - We show how the colloidal-probe technique, which is based on force measurements
made with the atomic force microscope, can be used to accurately determine the
charging parameters of water-solid interfaces. Besides yielding accurate values
of the double-layer or diffuse-layer potential, the method also allows reliable
determination of the charge regulation properties of the surfaces. The latter can
be quantified with a regulation parameter, which is essential to properly
describe forces between interfaces, especially in asymmetric situations when one
of the interfaces is charged and the other one is close to neutral. The technique
relies on a highly charged probe particle, for which the charging properties are
accurately determined by interpreting the double-layer contribution of the
measured force profiles in the symmetric sphere-sphere geometry with Poisson
Boltzmann (PB) theory. Once the probe particle is calibrated, this particle is
used to measure the force profile between an unknown substrate in the asymmetric
sphere-sphere or sphere-plane geometry. From this profile, the diffuse-layer
potential and regulation parameter of the substrate can be again determined with
PB theory. The technique is highly versatile, as it can be used for a wide
variety of substrates, including colloidal particles and planar substrates. The
technique is also applicable in salt solutions containing multivalent ions. The
current drawbacks of the technique are that it can only be applied up to
moderately high salt levels, typically to 10 mM, and only for relatively large
particles, typically down to about 1 MUm in diameter. How the technique could be
extended to higher salt levels and smaller particle size is also briefly
discussed.
PMID- 25122298
TI - Directional locking in deterministic lateral-displacement microfluidic separation
systems.
AB - We analyze the trajectory of suspended spherical particles moving through a
square array of obstacles, in the deterministic limit and at zero Reynolds
number. We show that in the dilute approximation of widely separated obstacles,
the average motion of the particles is equivalent to the trajectory followed by a
point particle moving through an array of obstacles with an effective radius. The
effective radius accounts for the hydrodynamic as well as short-range repulsive
nonhydrodynamic interactions between the suspended particles and the obstacles,
and is equal to the critical offset at which particle trajectories become
irreversible. Using this equivalent system we demonstrate the presence of
directional locking in the trajectory of the particles and derive an inequality
that accurately describes the "devil's staircase" type of structure observed in
the migration angle as a function of the forcing direction. We use these results
to determine the optimum resolution in the fractionation of binary mixtures using
deterministic lateral-displacement microfluidic separation systems as well as to
comment on the collision frequencies when the arrays of posts are utilized as
immunocapture devices.
PMID- 25122299
TI - Diffusing-wave spectroscopy in an inhomogeneous object: local viscoelastic
spectra from ultrasound-assisted measurement of correlation decay arising from
the ultrasound focal volume.
AB - We demonstrate diffusing-wave spectroscopy (DWS) in a localized region of a
viscoelastically inhomogeneous object by measurement of the intensity
autocorrelation [g(2)(tau)] that captures only the decay introduced by the
temperature-induced Brownian motion in the region. The region is roughly
specified by the focal volume of an ultrasound transducer which introduces region
specific mechanical vibration owing to insonification. Essential characteristics
of the localized non-Markovian dynamics are contained in the decay of the
modulation depth [M(tau)], introduced by the ultrasound forcing in the focal
volume selected, on g(2)(tau). The modulation depth M(tau(i)) at any delay time
tau(i) can be measured by short-time Fourier transform of g(2)(tau) and
measurement of the magnitude of the spectrum at the ultrasound drive frequency.
By following the established theoretical framework of DWS, we are able to connect
the decay in M(tau) to the mean-squared displacement (MSD) of scattering centers
and the MSD to G*(omega), the complex viscoelastic spectrum. A two-region
composite polyvinyl alcohol phantom with different viscoelastic properties is
selected for demonstrating local DWS-based recovery of G*(omega) corresponding to
these regions from the measured region specific M(tau(i))vstau(i). The ultrasound
assisted measurement of MSD is verified by simulating, using a generalized
Langevin equation (GLE), the dynamics of the particles in the region selected as
well as by the usual DWS experiment without the ultrasound. It is shown that
whereas the MSD obtained by solving the GLE without the ultrasound forcing agreed
with its experimental counterpart covering small and large values of tau, the
match was good only in the initial transients in regard to experimental
measurements with ultrasound.
PMID- 25122300
TI - Water electrolyte transport through corrugated carbon nanopores.
AB - We investigate the effect of wall roughness on water electrolyte transport
characteristics at different temperatures through carbon nanotubes by using
nonequilibrium molecular dynamics simulations. Our results reveal that shearing
stress and the nominal viscosity increase with ion concentration in corrugated
carbon nanotubes (CNTs), in contrast to cases in smooth CNTs. Also, the
temperature increase leads to the reduction of shearing stress and the nominal
viscosity at moderate degrees of wall roughness. At high degrees of wall
roughness, the temperature increase will enhance radial movements and increases
resistance against fluid motion. As the fluid velocity increases, the particles
do not have enough time to fully adjust their positions to minimize system
energy, which causes shearing stress and the nominal viscosity to increase. By
increasing roughness amplitude or decreasing roughness wavelength, the shearing
stress will increase. Synergistic effects of such parameters (wall roughness,
velocity, ion concentration, and temperature) inside corrugated CNTs are studied
and compared with each other. The molecular mechanisms are considered by
investigating the radial density profile and the radial velocity profile of
confined water inside modified CNT.
PMID- 25122301
TI - Phase behavior of a fluid with a double Gaussian potential displaying waterlike
features.
AB - Pair potentials that are bounded at the origin provide an accurate description of
the effective interaction for many systems of dissolved soft macromolecules
(e.g., flexible dendrimers). Using numerical free-energy calculations, we
reconstruct the equilibrium phase diagram of a system of particles interacting
through a potential that brings together a Gaussian repulsion with a much weaker
Gaussian attraction, close to the thermodynamic stability threshold. Compared to
the purely repulsive model, only the reentrant branch of the melting line
survives, since for lower densities solidification is overridden by liquid-vapor
separation. As a result, the phase diagram of the system recalls that of water up
to moderate (i.e., a few tens of MPa) pressures. Upon superimposing a suitable
hard core on the double-Gaussian potential, a further transition to a more
compact solid phase is induced at high pressure, which might be regarded as the
analog of the ice I-to-ice III transition in water.
PMID- 25122302
TI - Influence of primary-particle density in the morphology of agglomerates.
AB - Agglomeration processes occur in many different realms of science, such as
colloid and aerosol formation or formation of bacterial colonies. We study the
influence of primary-particle density in agglomerate structures using diffusion
controlled Monte Carlo simulations with realistic space scales through different
regimes (diffusion-limited aggregation and diffusion-limited colloid
aggregation). The equivalence of Monte Carlo time steps to real time scales is
given by Hirsch's hydrodynamical theory of Brownian motion. Agglomerate behavior
at different time stages of the simulations suggests that three indices (the
fractal exponent, the coordination number, and the eccentricity index)
characterize agglomerate geometry. Using these indices, we have found that the
initial density of primary particles greatly influences the final structure of
the agglomerate, as observed in recent experimental works.
PMID- 25122303
TI - Self-propelled particle transport in regular arrays of rigid asymmetric
obstacles.
AB - We report numerical results which show the achievement of net transport of self
propelled particles (SPPs) in the presence of a two-dimensional regular array of
convex, either symmetric or asymmetric, rigid obstacles. The repulsive
interparticle (soft disks) and particle-obstacle interactions present no
alignment rule. We find that SPPs present a vortex-type motion around convex
symmetric obstacles even in the absence of hydrodynamic effects. Such a motion is
not observed for a single SPP, but is a consequence of the collective motion of
SPPs around the obstacles. A steady particle current is spontaneously established
in an array of nonsymmetric convex obstacles (which presents no cavity in which
particles may be trapped), and in the absence of an external field. Our results
are mainly a consequence of the tendency of the self-propelled particles to
attach to solid surfaces.
PMID- 25122304
TI - Model for a mixture of macroions, counterions, and co-ions in a waterlike fluid.
AB - We propose an integral equation theory for a mixture of macroions, counterions,
and co-ions in a waterlike fluid in which all the components are accounted for
explicitly. The macroions can carry positive and negative surface charges
simultaneously, mimicking in this way the situation occurring in protein
solutions. To solve this complex model numerically, we utilize the associative
mean spherical approximation, developed earlier for low-molecular-mass charge
symmetric electrolyte solutions. To illustrate the potential of this approach, we
present numerical results for various experimental conditions. Among the
measurable properties we choose to calculate the osmotic coefficient, a quantity
that reflects the stability of the solution. We show that the osmotic coefficient
depends not only on the magnitude of the net charge on the macroion but also on
its sign, as well as on the nature of the low-molecular-mass electrolyte present.
These specific ion effects are the consequence of differences in hydration
between the ions in solution and charged groups on the macroion.
PMID- 25122305
TI - Characteristics of angular cross correlations studied by light scattering from
two-dimensional microsphere films.
AB - Recently the analysis of scattering patterns by angular cross-correlation
analysis (CCA) was introduced to reveal the orientational order in disordered
samples with special focus to future applications on x-ray free-electron laser
facilities. We apply this CCA approach to ultra-small-angle light-scattering data
obtained from two-dimensional monolayers of microspheres. The films were studied
in addition by optical microscopy. This combined approach allows to calculate the
cross-correlations of the scattering patterns, characterized by the orientational
correlation function Psi(l)(q), as well as to obtain the real-space structure of
the monolayers. We show that CCA is sensitive to the orientational order of
monolayers formed by the microspheres which are not directly visible from the
scattering patterns. By mixing microspheres of different radii the sizes of
ordered monolayer domains is reduced. For these samples it is shown that
Psi(l)(q) quantitatively describes the degree of hexagonal order of the two
dimensional films. The experimental CCA results are compared with calculations
based on the microscopy images. Both techniques show qualitatively similar
features. Differences can be attributed to the wave-front distortion of the laser
beam in the experiment. This effect is discussed by investigating the effect of
different wave fronts on the cross-correlation analysis results. The so
determined characteristics of the cross-correlation analysis will be also
relevant for future x-ray-based studies.
PMID- 25122306
TI - How nonmagnetic particles intensify rotational diffusion in magnetorheological
fluids.
AB - In this work we propose a mechanism to explain the enhancement of the magnetic
field-induced yield stress when nonmagnetic particles are added to magnetic
particulate suspensions, i.e., two-component suspensions. Our main hypothesis is
that the nonmagnetic particles collide with the field-induced magnetic aggregates
under shear flow. Consequently, supplementary fluctuations of the orientations of
the magnetic aggregates occur, resulting in an effective rotary diffusion
process, which increases the dynamic yield stress of the suspension. Furthermore,
the collision rate and the rotary diffusivity of the aggregates should increase
with the concentration of nonmagnetic particles. Rheological measurements in
plate-plate and cylindrical Couette geometries confirm the increase of the yield
stress with the volume fraction of nonmagnetic particles. In addition, such an
effect appears to be more important in Couette geometry, for which orientation
fluctuations of the magnetic aggregates play a more significant role. Finally, a
theoretical model based on this rotary diffusion mechanism is developed,
providing a quantitative explanation of the experimentally observed trends.
PMID- 25122307
TI - Surface shear-transformation zones in amorphous solids.
AB - We perform a systematic study of the characteristics of shear transformation
zones (STZs) that nucleate at free surfaces of two-dimensional amorphous solids
subject to tensile loading using two different atomistic simulation methods, the
standard athermal, quasistatic (AQ) approach and our recently developed self
learning metabasin escape (SLME) method, to account for the finite temperature
and strain-rate effects. In the AQ, or strain-driven limit, the nonaffine
displacement fields of surface STZs decay exponentially away from their centers
at similar decay rates as their bulk counterparts, though the direction of
maximum nonaffine displacement is tilted away from the tensile axis due to
surface effects. Using the SLME method at room temperature and at the high strain
rates that are seen in classical molecular dynamics simulations, the
characteristics for both bulk and surface STZs are found to be identical to those
seen in the AQ simulations. However, using the SLME method at room temperature
and experimentally relevant strain rates, we find a transition in the surface STZ
characteristics where a loss in the characteristic angular tensile-compression
symmetry is observed. Finally, the thermally activated surface STZs exhibit a
slower decay rate in the nonaffine displacement field than do strain-driven
surface STZs, which is characterized by a larger drop in potential energy
resulting from STZ nucleation that is enabled by the relative compliance of the
surface as compared to the bulk.
PMID- 25122308
TI - Interplay of model ingredients affecting aggregate shape plasticity in diffusion
limited aggregation.
AB - We analyze the combined effect of three ingredients of an aggregation model-
surface tension, particle flow and particle source--representing typical
characteristics of many aggregation growth processes in nature. Through extensive
numerical experiments and for different underlying lattice structures we
demonstrate that the location of incoming particles and their preferential
direction of flow can significantly affect the resulting general shape of the
aggregate, while the surface tension controls the surface roughness. Combining
all three ingredients increases the aggregate shape plasticity, yielding a wider
spectrum of shapes as compared to earlier works that analyzed these ingredients
separately. Our results indicate that the considered combination of effects is
fundamental for modeling the polymorphic growth of a wide variety of structures
in confined geometries and/or in the presence of external fields, such as rocks,
crystals, corals, and biominerals.
PMID- 25122309
TI - Phase-field modeling of grain-boundary premelting using obstacle potentials.
AB - We investigate the multiorder parameter phase field model of Steinbach and
Pezzolla [Physica D 134, 385 (1999)] concerning its ability to describe grain
boundary premelting. For a single order parameter situation solid-melt interfaces
are always attractive, which allows us to have (unstable) equilibrium solid-melt
solid coexistence above the bulk melting point. The temperature-dependent melt
layer thickness and the disjoining potential, which describe the interface
interaction, are affected by the choice of the thermal coupling function and the
measure to define the amount of the liquid phase. Due to the strictly finite
interface thickness the interaction range also is finite. For a multiorder
parameter model we find either purely attractive or purely repulsive finite
ranged interactions. The premelting transition is then directly linked to the
ratio of the grain boundary and solid-melt interfacial energy.
PMID- 25122310
TI - Thermally activated depinning motion of contact lines in pseudopartial wetting.
AB - We investigate pressure-driven motion of liquid-liquid menisci in circular tubes,
for systems in pseudopartial wetting conditions. The originality of this type of
wetting lies in the coexistence of a macroscopic contact angle with a wetting
liquid film covering the solid surface. Focusing on small capillary numbers, we
report observations of an apparent contact angle hysteresis at first sight
similar to the standard partial wetting case. However, this apparent hysteresis
exhibits original features. We observe very long transient regimes before steady
state, up to several hundreds of seconds. Furthermore, in steady state, the
velocities are nonzero, meaning that the contact line is not strongly pinned to
the surface defects, but are very small. The velocity of the contact line tends
to vanish near the equilibrium contact angle. These observations are consistent
with the thermally activated depinning theory that has been proposed to describe
partial wetting systems on disordered substrates and suggest that a single
physical mechanism controls both the hysteresis (or the pinning) and the motion
of the contact line. The proposed analysis leads to the conclusion that the
depinning activated energy is lower with pseudopartial wetting systems than with
partial wetting ones, allowing the direct observation of the thermally activated
motion of the contact line.
PMID- 25122311
TI - Self-similarity and scaling of thermal shock fractures.
AB - The problem of crack pattern formation due to thermal shock loading at the
surface of half space is solved numerically using the two-dimensional boundary
element method. The results of numerical simulations with 100-200 random
simultaneously growing and interacting cracks are used to obtain scaling
relations for crack length and spacing. The numerical results predict that such a
process of pattern formation with quasistatic crack growth is not stable and at
some point the excess energy leads to unstable propagation of one of the longest
cracks. This single-crack scenario should be understood in a local sense. There
could be other unstable cracks far away that together can form a new pattern. The
onset of instability has also been determined from numerical results.
PMID- 25122312
TI - Boundary lubrication with a liquid crystal monolayer.
AB - We study boundary lubrication characteristics of a liquid crystal (LC) monolayer
sheared between two crystalline surfaces by nonequilibrium molecular dynamics
simulations, using a simplified rigid bead-necklace model of the LC molecules. We
consider LC monolayers confined by surfaces with three different atomic
structures, subject to different shearing velocities, thus approximating a wide
variety of materials and driving conditions. The time dependence of the friction
force is studied and correlated with that of the orientational order exhibited by
the LC molecules, arising from the competition between the effect of the
structure of the confining surfaces and that of the imposed sliding direction. We
show that the observed stick-slip events for low shear rates involve order
disorder transitions, and that the LC monolayer no longer has enough time to
reorder at high shear rates, resulting in a smooth sliding regime. An irregular
stick-slip phase between the regular stick-slip and smooth sliding is observed
for intermediate shear rates regardless of the surface structure.
PMID- 25122313
TI - High-speed atomic force microscope imaging: adaptive multiloop mode.
AB - In this paper, an imaging mode (called the adaptive multiloop mode) of atomic
force microscope (AFM) is proposed to substantially increase the speed of tapping
mode (TM) imaging while preserving the advantages of TM imaging over contact mode
(CM) imaging. Due to its superior image quality and less sample disturbances over
CM imaging, particularly for soft materials such as polymers, TM imaging is
currently the most widely used imaging technique. The speed of TM imaging,
however, is substantially (over an order of magnitude) lower than that of CM
imaging, becoming the major bottleneck of this technique. Increasing the speed of
TM imaging is challenging as a stable probe tapping on the sample surface must be
maintained to preserve the image quality, whereas the probe tapping is rather
sensitive to the sample topography variation. As a result, the increase of
imaging speed can quickly lead to loss of the probe-sample contact and/or
annihilation of the probe tapping, resulting in image distortion and/or sample
deformation. The proposed adaptive multiloop mode (AMLM) imaging overcomes these
limitations of TM imaging through the following three efforts integrated
together: First, it is proposed to account for the variation of the TM deflection
when quantifying the sample topography; second, an inner-outer feedback control
loop to regulate the TM deflection is added on top of the tapping-feedback
control loop to improve the sample topography tracking; and, third, an online
iterative feedforward controller is augmented to the whole control system to
further enhance the topography tracking, where the next-line sample topography is
predicted and utilized to reduce the tracking error. The added feedback
regulation of the TM deflection ensures the probe-sample interaction force
remains near the minimum for maintaining a stable probe-sample interaction. The
proposed AMLM imaging is tested and demonstrated by imaging a poly(tert-butyl
acrylate) sample in experiments. The experimental results demonstrate that the
image quality achieved by using the proposed AMLM imaging at a scan rate of 25 Hz
and over a large-size imaging (50 MUm * 25 MUm) is at the same level of that
obtained using TM imaging at 1 Hz, while the probe-sample interaction force is
noticeably reduced from that achieved using TM imaging at 2.5 Hz.
PMID- 25122314
TI - Contact angle hysteresis and pinning at periodic defects in statics.
AB - This article deals with the theoretical prediction of the wetting hysteresis on
nonideal solid surfaces in terms of the surface heterogeneity parameters. The
spatially periodical chemical heterogeneity is considered. We propose precise
definitions for both the advancing and the receding contact angles for the
Wilhelmy plate geometry. It is well known that in such a system, a multitude of
metastable states of the liquid meniscus occurs for each different relative
position of the defect pattern on the plate with respect to the liquid level. As
usual, the static advancing and receding angles are assumed to be a consequence
of the preceding contact line motion in the respective direction. It is shown how
to select the appropriate states among all metastable states. Their selection is
discussed. The proposed definitions are applicable to both the static and the
dynamic contact angles on heterogeneous surfaces. The static advancing and
receding angles are calculated for two examples of periodic heterogeneity
patterns with sharp borders: the horizontal alternating stripes of a different
wettability (studied analytically) and the doubly periodic pattern of circular
defects on a homogeneous base (studied numerically). The wetting hysteresis is
determined as a function of the defect density and the spatial period. A
comparison with the existing results is carried out.
PMID- 25122315
TI - Sharp interfaces in two-dimensional free boundary problems: interface calculation
via matched conformal maps.
AB - We use conformal maps to study a free boundary problem for a two-fluid
electromechanical system, where the interface between the fluids is determined by
the combined effects of electrostatic forces, gravity, and surface tension. The
free boundary in our system develops sharp corners or singularities in certain
parameter regimes, and this is an impediment to using existing "single-scale"
numerical conformal mapping methods. The difficulty is due to the phenomenon of
crowding, i.e., the tendency of nodes in the preimage plane to concentrate near
the sharp regions of the boundary, leaving the smooth regions of the boundary
poorly resolved. A natural idea is to exploit the scale separation between the
sharp regions and smooth regions to solve for each region separately and then
stitch the solutions together. However, this is not straightforward as conformal
maps are rigid "global" objects, and it is not obvious how one would patch two
conformal maps together to obtain a new conformal map. We develop a "multiscale"
(i.e., adaptive) conformal mapping method that allows us to carry out this
program of stitching conformal maps on different scales together. We successfully
apply our method to the electromechanical model problem.
PMID- 25122316
TI - Damage accumulation in quasibrittle fracture.
AB - The strength of quasibrittle materials depends on the ensemble of defects inside
the sample and on the way damage accumulates before failure. Using large-scale
numerical simulations of the random fuse model, we investigate the evolution of
the microcrack distribution as the applied load approaches the fracture point. We
find that the distribution broadens mostly due to a tendency of cracks to
coalesce in a way that increases with system size. We study how the observed
behavior depends on the disorder present in the sample and relate the results
with fracture size effects.
PMID- 25122317
TI - Dewetting of evaporating thin films over nanometer-scale topographies.
AB - A lubrication model is used to study dewetting of an evaporating thin film layer
over a solid substrate with a nanometer-scale topography. The effects of the
geometry of the topography, the contact angle, the film thickness, and the
slippage on the dewetting have been studied. Our results reveal that the
evaporation enhances the dewetting process and reduces the depinning time over
the topography. Also it is shown that the depinning time is inversely
proportional to the slippage and increasing the contact angle may considerably
reduce the depinning time, while the film thickness increases the depinning time.
PMID- 25122318
TI - Equilibrium configurations of nematic liquid crystals on a torus.
AB - The topology and the geometry of a surface play a fundamental role in determining
the equilibrium configurations of thin films of liquid crystals. We propose here
a theoretical analysis of a recently introduced surface Frank energy, in the case
of two-dimensional nematic liquid crystals coating a toroidal particle. Our aim
is to show how a different modeling of the effect of extrinsic curvature acts as
a selection principle among equilibria of the classical energy and how new
configurations emerge. In particular, our analysis predicts the existence of
stable equilibria with complex windings.
PMID- 25122319
TI - Dynamics of colloidal particles in electrohydrodynamic convection of nematic
liquid crystal.
AB - We have studied the dynamics of micrometer-sized colloidal particles in
electrohydrodynamic convection of nematic liquid crystal. Above the onset voltage
of electroconvection, the parallel array of convection rolls appears to be
perpendicular to the nematic field at first. The particles are forced to rotate
by convection flow and are trapped within a single roll in this voltage regime. A
slow glide motion along the roll axis is also observed. The frequency of
rotational motion and the glide velocity increase with the applied voltage. Under
a much larger voltage where the roll axis temporally fluctuates, the particles
occasionally hop to the neighbor rolls. In this voltage regime, the motion of the
particles becomes two-dimensional. The motion perpendicular to the roll axis
exhibits diffusion behavior at a long time period. The effective diffusion
constant is 10(3)-10(4) times larger than the molecular one. The observed
behavior is compared with the result obtained by a simple stochastic model for
the transport of the particles in convection. The enhancement of diffusion can be
quantitatively described well by the rotation frequency in a roll, the width of
the roll, and the hopping probability to the neighbor rolls.
PMID- 25122320
TI - Electric-field variations within a nematic-liquid-crystal layer.
AB - A thin layer of nematic liquid crystal (NLC) across which an electric field is
applied is a setup of great industrial importance in liquid crystal display
devices. There is thus a large literature modeling this situation and related
scenarios. A commonly used assumption is that an electric field generated by
electrodes at the two bounding surfaces of the layer will produce a field that is
uniform: that is, the presence of NLC does not affect the electric field. In this
paper, we use calculus of variations to derive the equations coupling the
electric potential to the orientation of the NLC's director field, and use a
simple one-dimensional model to investigate the limitations of the uniform field
assumption in the case of a steady applied field. The extension of the model to
the unsteady case is also briefly discussed.
PMID- 25122321
TI - Gold nanoparticle liquid crystal composites as a tunable nonlinear medium.
AB - We investigate the nonlinearity of a liquid crystal cell doped with gold
nanoparticles by considering their selective absorption. Such nonlinearities are
promising for optical processing applications and optical limiters. Systems
displaying thermal nonlinearities are particularly attractive as the maximum
nonlinearity may occur in the absence of an applied field and additionally this
nonlinearity can be controlled by the reorientation of the liquid crystal. We
show that there exists a theoretical optimum concentration of absorbers, which
maximizes the nonlinearity. Further we show that the nonlinearity of the system
can be tuned by the reorientation of the liquid crystal host, with the
nonlinearity decreasing from 9 * 10(-5) cm(2)W(-1) to zero by the application of
a magnetic field of the order of 0.01 Tesla. This allows a fine control of the
diffraction efficiency and, in principle, many other nonlinear effects.
PMID- 25122322
TI - Two-dimensional skyrmions and other solitonic structures in confinement
frustrated chiral nematics.
AB - We explore spatially localized solitonic configurations of a director field,
generated using optical realignment and laser-induced heating, in frustrated
chiral nematic liquid crystals confined between substrates with perpendicular
surface anchoring. We demonstrate that, in addition to recently studied torons
and Hopf-fibration solitonic structures (hopfions), one can generate a host of
other axially symmetric stable and metastable director field configurations where
local twist is matched to the surface boundary conditions through introduction of
point defects and loops of singular and nonsingular disclinations. The
experimentally demonstrated structures include the so-called "baby-skyrmions" in
the form of double twist cylinders oriented perpendicular to the confining
substrates where their double twist field configuration is matched to the
perpendicular boundary conditions by loops of twist disclinations. We also
generate complex textures with arbitrarily large skyrmion numbers. A simple back
of-the-envelope theoretical analysis based on free energy considerations and the
nonpolar nature of chiral nematics provides insights into the long-term stability
and diversity of these inter-related solitonic field configurations, including
different types of torons, cholestric-finger loops, two-dimensional skyrmions,
and more complex structures comprised of torons, hopfions, and various
disclination loops that are experimentally observed in a confinement-frustrated
chiral nematic system.
PMID- 25122323
TI - Rheology of twist-grain-boundary-A liquid crystals.
AB - We report studies on the rheological properties of a liquid crystalline analog of
Abrikosov phase in type-II superconductors known as twist-grain-boundary-A
(TGB(A)) phase. The TGB(A) phase shows a large apparent yield stress compared to
the cholesteric (N*) phase. The storage modulus (G') of the TGB(A) phase is
significantly larger than the loss modulus (G''). The dynamic relaxation
measurements indicate a solid-like behavior of N*, TGB(A), and smectic-C* phases.
The complex shear modulus of the TGB(A) phase exhibits a power-law behavior
G*(omega) ~ omega(alpha) with alpha ? 0.5. The relative amplitude of G' and G''
at various temperatures indicate that the enhanced elasticity of TGB(A) phase is
due to the structural defects.
PMID- 25122324
TI - Symmetry breaking of nematic umbilical defects through an amplitude equation.
AB - The existence, stability properties, and bifurcation diagram of the nematic
umbilical defects is studied. Close to the Freedericksz transition of nematic
liquid crystals with negative anisotropic dielectric constant and homeotropic
anchoring, an anisotropic Ginzburg-Landau equation for the amplitude of the tilt
of the director away from the vertical axis is derived by taking the three
dimensional (3D) to 2D limit of the Frank-Oseen model. The anisotropic Ginzburg
Landau equation allows us to reveal the mechanism of symmetry breaking of nematic
umbilical defects. The positive defect is fully characterized as a function of
the anisotropy, while the negative defect is characterized perturbatively.
Numerical simulations show quite good agreement with the analytical results.
PMID- 25122325
TI - Comparative studies on field-induced stretching behavior of single-walled and
multiwalled carbon nanotube clusters.
AB - We demonstrate distinct entanglement of single-walled carbon nanotube (SWCNT) and
multiwalled carbon nanotube (MWCNT) clusters in nematic liquid crystal medium
using scanning electron microscopy technique and the entanglement influence on
electric field-induced stretching phenomena of the said clusters in the same
medium under optical microscopy investigation. The observed stretching threshold
field for MWCNT clusters is found to be higher than the SWCNT counterpart caused
by the interplay between attractive field-induced dipolar interaction of
intercarbon nanotube (CNT) bundles and the distinct degree of entanglement of
neighboring CNT bundles. Subsequently observed different tensile elasticity
modulus results for different CNT kinds also confirm different CNT bundle
entanglement and attractive dipolar interaction between adjacent CNT bundles in
CNT clusters are responsible for distinct stretching threshold field behavior.
PMID- 25122326
TI - Coarse-grained molecular dynamics simulations of the tensile behavior of a
thermosetting polymer.
AB - Using a previously developed coarse-grained model, we conducted large-scale (~ 85
* 85 * 85 nm(3)) molecular dynamics simulations of uniaxial-strain deformation to
study the tensile behavior of an epoxy molding compound, epoxy phenol novolacs
(EPN) bisphenol A (BPA). Under the uniaxial-strain deformation, the material is
found to exhibit cavity nucleation and growth, followed by stretching of the
ligaments separated by the cavities, until the ultimate failure through ligament
scissions. The nucleation sites of cavities are rather random and the subsequent
cavity growth accounts for much (87%) of the volumetric change during the
uniaxial-strain deformation. Ultimate failure of the materials occurs when the
cavity volume fraction reaches ~ 60%. During the entire deformation process,
polymer strands in the network are continuously extended to their linear states
and broken in the postyielding strain hardening stage. When most of the strands
are stretched to their taut configurations, rapid scission of a large number of
strands occurs within a small strain increment, which eventually leads to
fracture. Finally, through extensive numerical simulations of various loading
conditions in addition to uniaxial strain, we find that yielding of the EPN-BPA
can be described by the pressure-modified von Mises yield criterion.
PMID- 25122327
TI - Healing of polymer interfaces: Interfacial dynamics, entanglements, and strength.
AB - Self-healing of polymer films often takes place as the molecules diffuse across a
damaged region, above their melting temperature. Using molecular dynamics
simulations we probe the healing of polymer films and compare the results with
those obtained for thermal welding of homopolymer slabs. These two processes
differ from each other in their interfacial structure since damage leads to
increased polydispersity and more short chains. A polymer sample was cut into two
separate films that were then held together in the melt state. The recovery of
the damaged film was followed as time elapsed and polymer molecules diffused
across the interface. The mass uptake and formation of entanglements, as obtained
from primitive path analysis, are extracted and correlated with the interfacial
strength obtained from shear simulations. We find that the diffusion across the
interface is significantly faster in the damaged film compared to welding because
of the presence of short chains. Though interfacial entanglements increase more
rapidly for the damaged films, a large fraction of these entanglements are near
chain ends. As a result, the interfacial strength of the healing film increases
more slowly than for welding. For both healing and welding, the interfacial
strength saturates as the bulk entanglement density is recovered across the
interface. However, the saturation strength of the damaged film is below the bulk
strength for the polymer sample. At saturation, cut chains remain near the
healing interface. They are less entangled and as a result they mechanically
weaken the interface. Chain stiffness increases the density of entanglements,
which increases the strength of the interface. Our results show that a few
entanglements across the interface are sufficient to resist interfacial chain
pullout and enhance the mechanical strength.
PMID- 25122328
TI - Electrets in soft materials: nonlinearity, size effects, and giant
electromechanical coupling.
AB - Development of soft electromechanical materials is critical for several
tantalizing applications such as soft robots and stretchable electronics, among
others. Soft nonpiezoelectric materials can be coaxed to behave like
piezoelectrics by merely embedding charges and dipoles in their interior and
assuring some elastic heterogeneity. Such so-called electret materials have been
experimentally shown to exhibit very large electromechanical coupling. In this
work, we derive rigorous nonlinear expressions that relate effective
electromechanical coupling to the creation of electret materials. In contrast to
the existing models, we are able to both qualitatively and quantitatively capture
the known experimental results on the nonlinear response of electret materials.
Furthermore, we show that the presence of another form of electromechanical
coupling, flexoelectricity, leads to size effects that dramatically alter the
electromechanical response at submicron feature sizes. One of our key conclusions
is that nonlinear deformation (prevalent in soft materials) significantly
enhances the flexoelectric response and hence the aforementioned size effects.
PMID- 25122329
TI - Active matter transport and jamming on disordered landscapes.
AB - We numerically examine the transport of active run-and-tumble particles with
steric particle-particle interactions driven with a drift force over random
disordered landscapes composed of fixed obstacles. For increasing run lengths,
the net particle transport initially increases before reaching a maximum and
decreasing at larger run lengths. The transport reduction is associated with the
formation of cluster or living crystal states that become locally jammed or
clogged by the obstacles. We also find that the system dynamically jams at lower
particle densities when the run length is increased. Our results indicate that
there is an optimal activity level for transport of run-and-tumble type active
matter through quenched disorder and could be important for understanding
biological transport in complex environments or for applications of active matter
particles in random media.
PMID- 25122330
TI - Linear noise approximation for oscillations in a stochastic inhibitory network
with delay.
AB - Understanding neural variability is currently one of the biggest challenges in
neuroscience. Using theory and computational modeling, we study the behavior of a
globally coupled inhibitory neural network, in which each neuron follows a purely
stochastic two-state spiking process. We investigate the role of both this
intrinsic randomness and the conduction delay on the emergence of fast (e.g.,
gamma) oscillations. Toward that end, we expand the recently proposed linear
noise approximation (LNA) technique to this non-Markovian "delay" case. The
analysis first leads to a nonlinear delay-differential equation (DDE) with
multiplicative noise for the mean activity. The LNA then yields two coupled DDEs,
one of which is driven by additive Gaussian white noise. These equations on their
own provide an excellent approximation to the full network dynamics, which are
much longer to integrate. They further allow us to compute a theoretical
expression for the power spectrum of the population activity. Our analytical
result is in good agreement with the power spectrum obtained via numerical
simulations of the full network dynamics, for the large range of parameters where
both the intrinsic stochasticity and the conduction delay are necessary for the
occurrence of oscillations. The intrinsic noise arises from the probabilistic
description of each neuron, yet it is expressed at the system activity level, and
it can only be controlled by the system size. In fact, its effect on the
fluctuations in system activity disappears in the infinite network size limit,
but the characteristics of the oscillatory activity depend on all model
parameters including the system size. Using the Hilbert transform, we further
show that the intrinsic noise causes sporadic strong fluctuations in the phase of
the gamma rhythm.
PMID- 25122331
TI - Reconstruction of network structures from repeating spike patterns in simulated
bursting dynamics.
AB - Repeating patterns of spike sequences from a neuronal network have been proposed
to be useful in the reconstruction of the network topology. Reverberations in a
physiologically realistic model with various physical connection topologies (from
random to scale free) have been simulated to study the effectiveness of the
pattern-matching method in the reconstruction of network topology from network
dynamics. Simulation results show that functional networks reconstructed from
repeating spike patterns can be quite different from the original physical
networks; even global properties, such as the degree distribution, cannot always
be recovered. However, the pattern-matching method can be effective in
identifying hubs in the network. Since the form of reverberations is quite
different for networks with and without hubs, the form of reverberations together
with the reconstruction by repeating spike patterns might provide a reliable
method to detect hubs in neuronal cultures.
PMID- 25122332
TI - Swimming efficiency of spherical squirmers: beyond the Lighthill theory.
AB - Nonreciprocal shape deformations can drive inertialess cellular swimming, as
first explored by Taylor and Lighthill in the 1950s, for the small-amplitude
squirming of a planar and a spherical surface, respectively. Lighthill's
squirmer, in particular, has been extensively studied for large wave numbers in
the context of ciliated microbes. The maximal power efficiency for small
amplitude planar squirming motility is well characterized and degenerate, with
nonunique optimal swimming strokes. We explicitly show that this degeneracy is
retained at high wave numbers for the small-amplitude spherical squirmer such as
a ciliated microbe but is broken for low wave numbers. Hence further complexity
emerges in parameter regimes outside that of ciliate swimming even at small
amplitudes. Large-amplitude squirming also characterizes more recent observations
of large-amplitude/low-wave-number membrane deformations driving the motility of
Euglena, neutrophils, and Dictyostelium discoideum. Thus boundary element
numerical methods are used to explore swimming with increased deformation
amplitudes, especially in the context of power efficiency and swimming
performance. As radial squirming amplitudes are increased, small-amplitude
linearized theories can be unreliable even for nominally low deformation
amplitudes. Furthermore, even for a simple single-mode metachronal wave, a highly
motile and efficient large-deformation/small-wave-number swimming modality
arises, which can surpass theoretical limitations of purely tangential squirming
given a constrained surface deformation velocity.
PMID- 25122333
TI - Numerical simulation of the pairwise interaction of deformable cells during
migration in a microchannel.
AB - Leukocytes and other circulating cells deform and move relatively to the channel
flow in the lateral and translational directions. Their migratory property is
important in immune response, hemostasis, cancer progression, delivery of
nutrients, and microfluidic technologies such as cell separation and enrichment,
and flow cytometry. Using our three-dimensional computational algorithm for
multiphase viscoelastic flow, we have investigated the effect of pairwise
interaction on the lateral and translational migration of circulating cells in a
microchannel. The numerical simulation data show that when two cells with the
same size and small separation distance interact, repulsive interaction take
place until they reach the same lateral equilibrium position. During this
process, they undergo swapping or passing, depending on the initial separation
distance between each other. The threshold value of this distance increases with
cell deformation, indicating that the cells experiencing larger deformation are
more likely to swap. When a series of closely spaced cells with the same size are
considered, they generally undergo damped oscillation in both lateral and
translational directions until they reach equilibrium positions where they become
evenly distributed in the flow direction (self-assembly phenomenon). A series of
cells with a large lateral separation distance could collide repeatedly with each
other, eventually crossing the centerline and entering the other side of the
channel. For a series of cells with different deformability, more deformable
cells, upon impact with less deformable cells, move to an equilibrium position
closer to the centerline. The results of our study show that the bulk deformation
of circulating cells plays a key role in their migration in a microchannel.
PMID- 25122334
TI - Control of cardiac alternans by mechanical and electrical feedback.
AB - A persistent alternation in the cardiac action potential duration has been linked
to the onset of ventricular arrhythmia, which may lead to sudden cardiac death. A
coupling between these cardiac alternans and the intracellular calcium dynamics
has also been identified in previous studies. In this paper, the system of PDEs
describing the small amplitude of alternans and the alternation of peak
intracellular Ca(2+) are stabilized by optimal boundary and spatially distributed
actuation. A simulation study demonstrating the successful annihilation of both
alternans on a one-dimensional cable of cardiac cells by utilizing the full-state
feedback controller is presented. Complimentary to these studies, a three
variable Nash-Panfilov model is used to investigate alternans annihilation via
mechanical (or stretch) perturbations. The coupled model includes the active
stress which defines the mechanical properties of the tissue and is utilized in
the feedback algorithm as an independent input from the pacing based controller
realization in alternans annihilation. Simulation studies of both control methods
demonstrate that the proposed methods can successfully annihilate alternans in
cables that are significantly longer than 1 cm, thus overcoming the limitations
of earlier control efforts.
PMID- 25122336
TI - Inferring the origin of an epidemic with a dynamic message-passing algorithm.
AB - We study the problem of estimating the origin of an epidemic outbreak: given a
contact network and a snapshot of epidemic spread at a certain time, determine
the infection source. This problem is important in different contexts of computer
or social networks. Assuming that the epidemic spread follows the usual
susceptible-infected-recovered model, we introduce an inference algorithm based
on dynamic message-passing equations and we show that it leads to significant
improvement of performance compared to existing approaches. Importantly, this
algorithm remains efficient in the case where the snapshot sees only a part of
the network.
PMID- 25122335
TI - Determination of effective brain connectivity from functional connectivity with
application to resting state connectivities.
AB - Neural field theory insights are used to derive effective brain connectivity
matrices from the functional connectivity matrix defined by activity covariances.
The symmetric case is exactly solved for a resting state system driven by white
noise, in which strengths of connections, often termed effective connectivities,
are inferred from functional data; these include strengths of connections that
are underestimated or not detected by anatomical imaging. Proximity to
criticality is calculated and found to be consistent with estimates obtainable
from other methods. Links between anatomical, effective, and functional
connectivity and resting state activity are quantified, with applicability to
other complex networks. Proof-of-principle results are illustrated using
published experimental data on anatomical connectivity and resting state
functional connectivity. In particular, it is shown that functional connection
matrices can be used to uncover the existence and strength of connections that
are missed from anatomical connection matrices, including interhemispheric
connections that are difficult to track with techniques such as diffusion
spectrum imaging.
PMID- 25122337
TI - Voter model on the two-clique graph.
AB - I examine the mean consensus time (i.e., exit time) of the voter model in the so
called two-clique graph. The two-clique graph is composed of two cliques
interconnected by some links and considered as a toy model of networks with
community structure or multilayer networks. I analytically show that, as the
number of interclique links per node is varied, the mean consensus time
experiences a crossover between a fast consensus regime [i.e., O(N)] and a slow
consensus regime [i.e., O(N(2))], where N is the number of nodes. The fast regime
is consistent with the result for homogeneous well-mixed graphs such as the
complete graph. The slow regime appears only when the entire network has O(1)
interclique links. The present results suggest that the effect of community
structure on the consensus time of the voter model is fairly limited.
PMID- 25122338
TI - Simultaneous first- and second-order percolation transitions in interdependent
networks.
AB - In a system of interdependent networks, an initial failure of nodes invokes a
cascade of iterative failures that may lead to a total collapse of the whole
system in the form of an abrupt first-order transition. When the fraction of
initial failed nodes 1-p reaches criticality p = p(c), the abrupt collapse occurs
by spontaneous cascading failures. At this stage, the giant component decreases
slowly in a plateau form and the number of iterations in the cascade tau
diverges. The origin of this plateau and its increasing with the size of the
system have been unclear. Here we find that, simultaneously with the abrupt first
order transition, a spontaneous second-order percolation occurs during the
cascade of iterative failures. This sheds light on the origin of the plateau and
how its length scales with the size of the system. Understanding the critical
nature of the dynamical process of cascading failures may be useful for designing
strategies for preventing and mitigating catastrophic collapses.
PMID- 25122339
TI - Geometrical invariability of transformation between a time series and a complex
network.
AB - We present a dynamically equivalent transformation between time series and
complex networks based on coarse geometry theory. In terms of quasi-isometric
maps, we characterize how the underlying geometrical characters of complex
systems are preserved during transformations. Fractal dimensions are shown to be
the same for time series (or complex network) and its transformed counterpart.
Results from the Rossler system, fractional Brownian motion, synthetic networks,
and real networks support our findings. This work gives theoretical evidences for
an equivalent transformation between time series and networks.
PMID- 25122341
TI - Detecting network communities beyond assortativity-related attributes.
AB - In network science, assortativity refers to the tendency of links to exist
between nodes with similar attributes. In social networks, for example, links
tend to exist between individuals of similar age, nationality, location, race,
income, educational level, religious belief, and language. Thus, various
attributes jointly affect the network topology. An interesting problem is to
detect community structure beyond some specific assortativity-related attributes
rho, i.e., to take out the effect of rho on network topology and reveal the
hidden community structures which are due to other attributes. An approach to
this problem is to redefine the null model of the modularity measure, so as to
simulate the effect of rho on network topology. However, a challenge is that we
do not know to what extent the network topology is affected by rho and by other
attributes. In this paper, we propose a distance modularity, which allows us to
freely choose any suitable function to simulate the effect of rho. Such freedom
can help us probe the effect of rho and detect the hidden communities which are
due to other attributes. We test the effectiveness of distance modularity on
synthetic benchmarks and two real-world networks.
PMID- 25122340
TI - Efficiently inferring community structure in bipartite networks.
AB - Bipartite networks are a common type of network data in which there are two types
of vertices, and only vertices of different types can be connected. While
bipartite networks exhibit community structure like their unipartite
counterparts, existing approaches to bipartite community detection have
drawbacks, including implicit parameter choices, loss of information through one
mode projections, and lack of interpretability. Here we solve the community
detection problem for bipartite networks by formulating a bipartite stochastic
block model, which explicitly includes vertex type information and may be
trivially extended to k-partite networks. This bipartite stochastic block model
yields a projection-free and statistically principled method for community
detection that makes clear assumptions and parameter choices and yields
interpretable results. We demonstrate this model's ability to efficiently and
accurately find community structure in synthetic bipartite networks with known
structure and in real-world bipartite networks with unknown structure, and we
characterize its performance in practical contexts.
PMID- 25122342
TI - Suppressing epidemics on networks by exploiting observer nodes.
AB - To control infection spreading on networks, we investigate the effect of observer
nodes that recognize infection in a neighboring node and make the rest of the
neighbor nodes immune. We numerically show that random placement of observer
nodes works better on networks with clustering than on locally treelike networks,
implying that our model is promising for realistic social networks. The
efficiency of several heuristic schemes for observer placement is also examined
for synthetic and empirical networks. In parallel with numerical simulations of
epidemic dynamics, we also show that the effect of observer placement can be
assessed by the size of the largest connected component of networks remaining
after removing observer nodes and links between their neighboring nodes.
PMID- 25122343
TI - Competing spreading processes on multiplex networks: awareness and epidemics.
AB - Epidemiclike spreading processes on top of multilayered interconnected complex
networks reveal a rich phase diagram of intertwined competition effects. A recent
study by the authors [C. Granell et al., Phys. Rev. Lett. 111, 128701 (2013).]
presented an analysis of the interrelation between two processes accounting for
the spreading of an epidemic, and the spreading of information awareness to
prevent infection, on top of multiplex networks. The results in the case in which
awareness implies total immunization to the disease revealed the existence of a
metacritical point at which the critical onset of the epidemics starts, depending
on completion of the awareness process. Here we present a full analysis of these
critical properties in the more general scenario where the awareness spreading
does not imply total immunization, and where infection does not imply immediate
awareness of it. We find the critical relation between the two competing
processes for a wide spectrum of parameters representing the interaction between
them. We also analyze the consequences of a massive broadcast of awareness (mass
media) on the final outcome of the epidemic incidence. Importantly enough, the
mass media make the metacritical point disappear. The results reveal that the
main finding, i.e., existence of a metacritical point, is rooted in the
competition principle and holds for a large set of scenarios.
PMID- 25122344
TI - Robustness of a network formed of spatially embedded networks.
AB - We present analytic and numeric results for percolation in a network formed of
interdependent spatially embedded networks. We show results for a treelike and a
random regular network of networks each with (i) unconstrained dependency links
and (ii) dependency links restricted to a maximum Euclidean length r. Analytic
results are given for each network of networks with spatially unconstrained
dependency links and compared to simulations. For the case of two fully
interdependent spatially embedded networks it was found [Li et al., Phys. Rev.
Lett. 108, 228702 (2012)] that the system undergoes a first-order phase
transition only for r>r(c) ~ 8. We find here that for treelike networks of
networks (composed of n networks) r(c) significantly decreases as n increases and
rapidly (n >= 11) reaches its limiting value of 1. For cases where the
dependencies form loops, such as in random regular networks, we show analytically
and confirm through simulations that there is a certain fraction of dependent
nodes, q(max), above which the entire network structure collapses even if a
single node is removed. The value of q(max) decreases quickly with m, the degree
of the random regular network of networks. Our results show the extreme
sensitivity of coupled spatial networks and emphasize the susceptibility of these
networks to sudden collapse. The theory proposed here requires only numerical
knowledge about the percolation behavior of a single network and therefore can be
used to find the robustness of any network of networks where the profile of
percolation of a singe network is known numerically.
PMID- 25122345
TI - Epidemic outbreaks in two-scale community networks.
AB - We consider a model for the diffusion of epidemics in a population that is
partitioned into local communities. In particular, assuming a mean-field
approximation, we analyze a continuous-time susceptible-infected-susceptible
(SIS) model that has appeared recently in the literature. The probability by
which an individual infects individuals in its own community is different from
the probability of infecting individuals in other communities. The aim of the
model, compared to the standard, nonclustered one, is to provide a compact
description for the presence of communities of local infection where the epidemic
process is faster compared to the rate at which it spreads across communities.
Ultimately, it provides a tool to express the probability of epidemic outbreaks
in the form of a metastable infection probability. In the proposed model, the
spatial structure of the network is encoded by the adjacency matrix of clusters,
i.e., the connections between local communities, and by the vector of the sizes
of local communities. Thus, the existence of a nontrivial metastable occupancy
probability is determined by an epidemic threshold which depends on the clusters'
size and on the intercommunity network structure.
PMID- 25122346
TI - General optimization technique for high-quality community detection in complex
networks.
AB - Recent years have witnessed the development of a large body of algorithms for
community detection in complex networks. Most of them are based upon the
optimization of objective functions, among which modularity is the most common,
though a number of alternatives have been suggested in the scientific literature.
We present here an effective general search strategy for the optimization of
various objective functions for community detection purposes. When applied to
modularity, on both real-world and synthetic networks, our search strategy
substantially outperforms the best existing algorithms in terms of final scores
of the objective function. In terms of execution time for modularity optimization
this approach also outperforms most of the alternatives present in literature
with the exception of fastest but usually less efficient greedy algorithms. The
networks of up to 30000 nodes can be analyzed in time spans ranging from minutes
to a few hours on average workstations, making our approach readily applicable to
tasks not limited by strict time constraints but requiring the quality of
partitioning to be as high as possible. Some examples are presented in order to
demonstrate how this quality could be affected by even relatively small changes
in the modularity score stressing the importance of optimization accuracy.
PMID- 25122348
TI - Effect of environment fluctuations on pattern formation of single species.
AB - System-environment interactions are intrinsically nonlinear and dependent on the
interplay between many degrees of freedom. The complexity may be even more
pronounced when one aims to describe biologically motivated systems. In that
case, it is useful to resort to simplified models relying on effective stochastic
equations. A natural consideration is to assume that there is a noisy
contribution from the environment, such that the parameters that characterize it
are not constant but instead fluctuate around their characteristic values. From
this perspective, we propose a stochastic generalization of the nonlocal Fisher
KPP equation where, as a first step, environmental fluctuations are Gaussian
white noises, both in space and time. We apply analytical and numerical
techniques to study how noise affects stability and pattern formation in this
context. Particularly, we investigate noise-induced coherence by means of the
complementary information provided by the dispersion relation and the structure
function.
PMID- 25122347
TI - Interplay of network dynamics and heterogeneity of ties on spreading dynamics.
AB - The structure of a network dramatically affects the spreading phenomena unfolding
upon it. The contact distribution of the nodes has long been recognized as the
key ingredient in influencing the outbreak events. However, limited knowledge is
currently available on the role of the weight of the edges on the persistence of
a pathogen. At the same time, recent works showed a strong influence of temporal
network dynamics on disease spreading. In this work we provide an analytical
understanding, corroborated by numerical simulations, about the conditions for
infected stable state in weighted networks. In particular, we reveal the role of
heterogeneity of edge weights and of the dynamic assignment of weights on the
ties in the network in driving the spread of the epidemic. In this context we
show that when weights are dynamically assigned to ties in the network, a
heterogeneous distribution is able to hamper the diffusion of the disease,
contrary to what happens when weights are fixed in time.
PMID- 25122349
TI - Parallel discrete-event simulation schemes with heterogeneous processing
elements.
AB - To understand the effects of nonidentical processing elements (PEs) on parallel
discrete-event simulation (PDES) schemes, two stochastic growth models, the
restricted solid-on-solid (RSOS) model and the Family model, are investigated by
simulations. The RSOS model is the model for the PDES scheme governed by the
Kardar-Parisi-Zhang equation (KPZ scheme). The Family model is the model for the
scheme governed by the Edwards-Wilkinson equation (EW scheme). Two kinds of
distributions for nonidentical PEs are considered. In the first kind computing
capacities of PEs are not much different, whereas in the second kind the
capacities are extremely widespread. The KPZ scheme on the complex networks shows
the synchronizability and scalability regardless of the kinds of PEs. The EW
scheme never shows the synchronizability for the random configuration of PEs of
the first kind. However, by regularizing the arrangement of PEs of the first
kind, the EW scheme is made to show the synchronizability. In contrast, EW scheme
never shows the synchronizability for any configuration of PEs of the second
kind.
PMID- 25122350
TI - Percolation on fitness-dependent networks with heterogeneous resilience.
AB - The ability to understand the impact of adversarial processes on networks is
crucial to various disciplines. The objects of study in this article are fitness
driven networks. Fitness-dependent networks are fully described by a probability
distribution of fitness and an attachment kernel. Every node in the network is
endowed with a fitness value and the attachment kernel translates the fitness of
two nodes into the probability that these two nodes share an edge. This concept
is also known as mutual attractiveness. In the present article, fitness does not
only serve as a measure of attractiveness, but also as a measure of a node's
robustness against failure. The probability that a node fails increases with the
number of failures in its direct neighborhood and decreases with higher fitness.
Both static and dynamic network models are considered. Analytical results for the
percolation threshold and the occupied fraction are derived. One of the results
is that the distinction between the dynamic and the static model has a profound
impact on the way failures spread over the network. Additionally, we find that
the introduction of mutual attractiveness stabilizes the network compared to a
pure random attachment.
PMID- 25122351
TI - Networks maximizing the consensus time of voter models.
AB - We explore the networks that yield the largest mean consensus time of voter
models under different update rules. By analytical and numerical means, we show
that the so-called lollipop graph, barbell graph, and double-star graph maximize
the mean consensus time under the update rules called the link dynamics, voter
model, and invasion process, respectively. For each update rule, the largest mean
consensus time scales as O(N^{3}), where N is the number of nodes in the network.
PMID- 25122352
TI - Hidden scaling patterns and universality in written communication.
AB - The temporal statistics exhibited by written correspondence appear to be media
dependent, with features which have so far proven difficult to characterize. We
explain the origin of these difficulties by disentangling the role of spontaneous
activity from decision-based prioritizing processes in human dynamics, clocking
all waiting times through each agent's "proper time" measured by activity. This
unveils the same fundamental patterns in written communication across all media
(letters, email, sms), with response times displaying truncated power-law
behavior and average exponents near -3/2. When standard time is used, the
response time probabilities are theoretically predicted to exhibit a bimodal
character, which is empirically borne out by our newly collected years-long data
on email. These perspectives on the temporal dynamics of human correspondence
should aid in the analysis of interaction phenomena in general, including
resource management, optimal pricing and routing, information sharing, and
emergency handling.
PMID- 25122353
TI - Transmission of linear regression patterns between time series: from relationship
in time series to complex networks.
AB - The linear regression parameters between two time series can be different under
different lengths of observation period. If we study the whole period by the
sliding window of a short period, the change of the linear regression parameters
is a process of dynamic transmission over time. We tackle fundamental research
that presents a simple and efficient computational scheme: a linear regression
patterns transmission algorithm, which transforms linear regression patterns into
directed and weighted networks. The linear regression patterns (nodes) are
defined by the combination of intervals of the linear regression parameters and
the results of the significance testing under different sizes of the sliding
window. The transmissions between adjacent patterns are defined as edges, and the
weights of the edges are the frequency of the transmissions. The major patterns,
the distance, and the medium in the process of the transmission can be captured.
The statistical results of weighted out-degree and betweenness centrality are
mapped on timelines, which shows the features of the distribution of the results.
Many measurements in different areas that involve two related time series
variables could take advantage of this algorithm to characterize the dynamic
relationships between the time series from a new perspective.
PMID- 25122354
TI - Modular networks with delayed coupling: synchronization and frequency control.
AB - We study the collective dynamics of modular networks consisting of map-based
neurons which generate irregular spike sequences. Three types of intramodule
topology are considered: a random Erdos-Renyi network, a small-world Watts
Strogatz network, and a scale-free Barabasi-Albert network. The interaction
between the neurons of different modules is organized by relatively sparse
connections with time delay. For all the types of the network topology
considered, we found that with increasing delay two regimes of module
synchronization alternate with each other: inphase and antiphase. At the same
time, the average rate of collective oscillations decreases within each of the
time-delay intervals corresponding to a particular synchronization regime. A dual
role of the time delay is thus established: controlling a synchronization mode
and degree and controlling an average network frequency. Furthermore, we
investigate the influence on the modular synchronization by other parameters: the
strength of intermodule coupling and the individual firing rate.
PMID- 25122355
TI - Solutions of the higher-order Manakov-type continuous and discrete equations.
AB - We derive exact and approximate localized solutions for the Manakov-type
continuous and discrete equations. We establish the correspondence between the
solutions of the coupled Ablowitz-Ladik equations and the solutions of the
coupled higher-order Manakov equations.
PMID- 25122356
TI - Dynamics in the Sakaguchi-Kuramoto model with two subpopulations [corrected].
AB - The dynamics in a variant of globally coupled Sakaguchi-Kuramoto [corrected].
phase oscillators is studied. The model consists of two subpopulations, each with
a different phase lag and interaction strength. Using Ott-Antonson ansatz, we
analyze the dynamics in the model and present the numerical results. There exist
stationary synchronous states which are generalized pi states and two types of
traveling wave states. We find that the traveling wave states are the dominant
dynamics in comparison with the stationary states. Particularly, we find that the
stationary and traveling wave states can be smoothly connected through the
properly chosen parameter paths.
PMID- 25122357
TI - Size-dependent diffusion promotes the emergence of spatiotemporal patterns.
AB - Spatiotemporal patterns, indicating the spatiotemporal variability of individual
abundance, are a pronounced scenario in ecological interactions. Most of the
existing models for spatiotemporal patterns treat species as homogeneous groups
of individuals with average characteristics by ignoring intraspecific
physiological variations at the individual level. Here we explore the impacts of
size variation within species resulting from individual ontogeny, on the
emergence of spatiotemporal patterns in a fully size-structured population model.
We found that size dependency of animal's diffusivity greatly promotes the
formation of spatiotemporal patterns, by creating regular spatiotemporal patterns
out of temporal chaos. We also found that size-dependent diffusion can substitute
large-amplitude base harmonics with spatiotemporal patterns with lower amplitude
oscillations but with enriched harmonics. Finally, we found that the single
generation cycle is more likely to drive spatiotemporal patterns compared to
predator-prey cycles, meaning that the mechanism of Hopf bifurcation might be
more common than hitherto appreciated since the former cycle is more widespread
than the latter in case of interacting populations. Due to the ubiquity of
individual ontogeny in natural ecosystems we conclude that diffusion variability
within populations is a significant driving force for the emergence of
spatiotemporal patterns. Our results offer a perspective on self-organized
phenomena, and pave a way to understand such phenomena in systems organized as
complex ecological networks.
PMID- 25122358
TI - Front propagation in a chaotic flow field.
AB - We investigate numerically the dynamics of a propagating front in the presence of
a spatiotemporally chaotic flow field. The flow field is the three-dimensional
time-dependent state of spiral defect chaos generated by Rayleigh-Benard
convection in a spatially extended domain. Using large-scale parallel numerical
simulations, we simultaneously solve the Boussinesq equations and a reaction
advection-diffusion equation with a Fischer-Kolmogorov-Petrovskii-Piskunov
reaction for the transport of the scalar species in a large-aspect-ratio
cylindrical domain for experimentally accessible conditions. We explore the front
dynamics and geometry in the low-Damkohler-number regime, where the effect of the
flow field is significant. Our results show that the chaotic flow field enhances
the front propagation when compared with a purely cellular flow field. We
quantify this enhancement by computing the spreading rate of the reaction
products for a range of parameters. We use our results to quantify the complexity
of the three-dimensional front geometry for a range of chaotic flow conditions.
PMID- 25122359
TI - Dynamics of impurities in a three-dimensional volume-preserving map.
AB - We study the dynamics of inertial particles in three-dimensional incompressible
maps, as representations of volume-preserving flows. The impurity dynamics has
been modeled, in the Lagrangian framework, by a six-dimensional dissipative
bailout embedding map. The fluid-parcel dynamics of the base map is embedded in
the particle dynamics governed by the map. The base map considered for the
present study is the Arnold-Beltrami-Childress (ABC) map. We consider the
behavior of the system both in the aerosol regime, where the density of the
particle is larger than that of the base flow, as well as the bubble regime,
where the particle density is less than that of the base flow. The phase spaces
in both the regimes show rich and complex dynamics with three types of dynamical
behaviors--chaotic structures, regular orbits, and hyperchaotic regions. In the
one-action case, the aerosol regime is found to have periodic attractors for
certain values of the dissipation and inertia parameters. For the aerosol regime
of the two-action ABC map, an attractor merging and widening crisis is identified
using the bifurcation diagram and the spectrum of Lyapunov exponents. After the
crisis an attractor with two parts is seen, and trajectories hop between these
parts with period 2. The bubble regime of the embedded map shows strong
hyperchaotic regions as well as crisis induced intermittency with characteristic
times between bursts that scale as a power law behavior as a function of the
dissipation parameter. Furthermore, we observe a riddled basin of attraction and
unstable dimension variability in the phase space in the bubble regime. The
bubble regime in the one-action case shows similar behavior. This study of a
simple model of impurity dynamics may shed light upon the transport properties of
passive scalars in three-dimensional flows. We also compare our results with
those seen earlier in two-dimensional flows.
PMID- 25122360
TI - Shallow-water soliton dynamics beyond the Korteweg-de Vries equation.
AB - An alternative way for the derivation of the new Korteweg-de Vries (KdV)-type
equation is presented. The equation contains terms depending on the bottom
topography (there are six new terms in all, three of which are caused by the
unevenness of the bottom). It is obtained in the second-order perturbative
approach in the weakly nonlinear, dispersive, and long wavelength limit. Only
treating all these terms in the second-order perturbation theory made the
derivation of this KdV-type equation possible. The motion of a wave, which starts
as a KdV soliton, is studied according to the new equation in several cases by
numerical simulations. The quantitative changes of a soliton's velocity and
amplitude appear to be directly related to bottom variations. Changes of the
soliton's velocity appear to be almost linearly anticorrelated with changes of
water depth, whereas correlation of variation of soliton's amplitude with changes
of water depth looks less linear. When the bottom is flat, the new terms narrow
down the family of exact solutions, but at least one single soliton survives.
This is also checked by numerics.
PMID- 25122361
TI - Symbolic dynamics-based error analysis on chaos synchronization via noisy
channels.
AB - In this study, symbolic dynamics is used to research the error of chaos
synchronization via noisy channels. The theory of symbolic dynamics reduces chaos
to a shift map that acts on a discrete set of symbols, each of which contains
information about the system state. Using this transformation, a coder-decoder
scheme is proposed. A model for the relationship among word length, region number
of a partition, and synchronization error is provided. According to the model,
the fundamental trade-off between word length and region number can be optimized
to minimize the synchronization error. Numerical simulations provide support for
our results.
PMID- 25122362
TI - Control for a synchronization-desynchronization switch.
AB - How to freely enhance or suppress synchronization of networked dynamical systems
is of great importance in many disciplines. A unified precise control method for
a synchronization-desynchronization switch, called the pull-push control method,
is suggested. Namely, synchronization can be achieved when the original systems
are desynchronous by pulling (or protecting) one node or a certain subset of
nodes, whereas desynchronization can be accomplished when the systems are already
synchronous by pushing (or kicking) one node or a certain subset of nodes. With
this method, the controlled nodes should be chosen by the generalized eigenvector
centrality of the critical synchronization mode of the Laplacian matrix. Compared
with existing control methods for synchronization, it displays high efficiency,
flexibility, and precision as well.
PMID- 25122363
TI - Electrokinetic instability near charge-selective hydrophobic surfaces.
AB - The influence of the texture of a hydrophobic surface on the electro-osmotic slip
of the second kind and the electrokinetic instability near charge selective
surfaces (permselective membranes, electrodes, or systems of microchannels and
nanochannels) is investigated theoretically using a simple model based on the
Rubinstein-Zaltzman approach. A simple formula is derived to evaluate the
decrease in the instability threshold due to hydrophobicity. The study is
complemented by numerical investigations both of linear and nonlinear
instabilities near a hydrophobic membrane surface. Theory predicts a significant
enhancement of the ion flux to the surface and shows a good qualitative agreement
with the available experimental data.
PMID- 25122364
TI - Chaotic motion of light particles in an unsteady three-dimensional vortex:
experiments and simulation.
AB - We study the chaotic motion of a small rigid sphere, lighter than the fluid in a
three-dimensional vortex of finite height. Based on the results of Eulerian and
Lagrangian measurements, a sequence of models is set up. The time-independent
model is a generalization of the Burgers vortex. In this case, there are two
types of attractors for the particle: a fixed point on the vortex axis and a
limit cycle around the vortex axis. Time dependence might combine these regular
attractors into a single chaotic attractor, however its robustness is much weaker
than what the experiments suggest. To construct an aperiodically time-dependent
advection dynamics in a simple way, Gaussian noise is added to the particle
velocity in the numerical simulation. With an appropriate choice of the noise
properties, mimicking the effect of local turbulence, a reasonable agreement with
the experimentally observed particle statistics is found.
PMID- 25122365
TI - Interfacial dynamics of two immiscible fluids in spatially periodic porous media:
the role of substrate wettability.
AB - We delineate the contact line dynamics of two immiscible fluids in a medium
having spatially periodic porous structures. The flow is driven by an external
applied pressure gradient. We bring out the combined consequences of the solid
fraction distribution and the substrate wettability on the resulting dynamics of
the contact line, by employing phase-field formalism. We capture the sequence of
spatiotemporal events leading to formation of liquid bridges by trapping a small
amount of displaced phase fluid between two consecutive porous blocks, as
dictated by the combinations of substrate wettability and solid fraction. We also
demonstrate the existence of a regime of complete interfacial recovery, depending
on the parametric space of the governing parameters under concern. Our results
essentially demonstrate the intricate mechanisms by virtue of which the
wettabilities of the substrates alter the dynamical evolutions of interfaces and
the subsequent shapes and sizes of the adsorbed dispersed phases, bearing far
ranging consequences in several practical applications ranging from oil recovery
to groundwater flow.
PMID- 25122366
TI - Magnetic energy dissipation and mean magnetic field generation in planar
convection-driven dynamos.
AB - A numerical study of dynamos in rotating convecting plane layers is presented
which focuses on magnetic energies and dissipation rates and the generation of
mean fields (where the mean is taken over horizontal planes). The scaling of the
magnetic energy with the flux Rayleigh number is different from the scaling
proposed in spherical shells, whereas the same dependence of the magnetic
dissipation length on the magnetic Reynolds number is found for the two
geometries. Dynamos both with and without mean field exist in rapidly rotating
convecting plane layers.
PMID- 25122367
TI - Nonaxisymmetric high-aspect-ratio ellipsoids under shear: lowest-order correction
for finite aspect ratios.
AB - We extend the classic study of the motion of small ellipsoidal particles under
shear, focusing on simplifications obtained by considerations of the extreme
aspect ratios typical of rheoscopic particles (e.g., Kalliroscope). Specifically,
we study conditions under which the long-time behavior of scalene (i.e., triaxial
or nonaxisymmetric) ellipsoids are well approximated by a model that is low order
in the appropriate aspect ratios. After enumerating and describing the generic
long-time motions of such particles in the lowest-order model, we investigate
corrections induced by the physically appropriate lowest-order correction to the
base model, with special attention to a periodic wobbling motion special to
scalene ellipsoids.
PMID- 25122368
TI - Finite time blow-up and breaking of solitary wind waves.
AB - The evolution of surface water waves in finite depth under wind forcing is
reduced to an antidissipative Korteweg-de Vries-Burgers equation. We exhibit its
solitary wave solution. Antidissipation accelerates and increases the amplitude
of the solitary wave and leads to blow-up and breaking. Blow-up occurs in finite
time for infinitely large asymptotic space so it is a nonlinear, dispersive, and
antidissipative equivalent of the linear instability which occurs for infinite
time. Due to antidissipation two given arbitrary and adjacent planes of constant
phases of the solitary wave acquire different velocities and accelerations
inducing breaking. Soliton breaking occurs in finite space in a time prior to the
blow-up. We show that the theoretical growth in amplitude and the time of
breaking are both testable in an existing experimental facility.
PMID- 25122369
TI - dc Step response of induced-charge electro-osmosis between parallel electrodes at
large voltages.
AB - Induced-charge electro-osmosis (ICEO) is important since it can be used for
realizing high performance microfluidic devices. Here, we analyze the simplest
problem of ion relaxation around a circular polarizable cylinder between parallel
blocking electrodes in a closed cell by using a multiphysics coupled simulation
technique. This technique is based on a combination of the finite-element method
and finite-volume method for the Poisson-Nernst-Planck (PNP) equations having a
flow term and the Stokes equation having an electric stress term. Through this
analysis, we successfully demonstrate that on application of dc voltages,
quadorapolar ICEO vortex flows grow during the charging time of the cylinder for
both unbounded and bounded problems and decay during the charging time of the
parallel electrodes only for the bounded problem using blocking electrodes.
Further, by proposing a simple model that considers the two-dimensional (2D) PNP
equations analytically, we successfully explain the step response time of the
ICEO flow for the both unbounded and bounded problems. Furthermore, at low
applied voltages, we find analytical formulations on steady diffused-ion problems
and steady ICEO-flow problems and examine that our numerical results agree well
with the analytical results. Moreover, by considering an ion-conserving condition
with 2D Poisson-Boltzmann equations, we explain significant decrease of the
maximum slip velocity at large applied voltages fairly well. We believe that our
analysis will contribute greatly to the realistic designs of prospective high
performance microfluidic devices.
PMID- 25122370
TI - Cyclones and attractive streaming generated by acoustical vortices.
AB - Acoustical and optical vortices have attracted great interest due to their
ability to capture and manipulate particles with the use of radiation pressure.
Here we show that acoustical vortices can also induce axial vortical flow
reminiscent of cyclones, whose topology can be controlled by adjusting the
properties of the acoustical beam. In confined geometry, the phase singularity
enables generating "attractive streaming" with the flow directed toward the
transducer. This opens perspectives for contactless vortical flow control.
PMID- 25122371
TI - Nonequilibrium shock-heated nitrogen flows using a rovibrational state-to-state
method.
AB - A rovibrational collisional model is developed to study the internal energy
excitation and dissociation processes behind a strong shock wave in a nitrogen
flow. The reaction rate coefficients are obtained from the ab initio database of
the NASA Ames Research Center. The master equation is coupled with a one
dimensional flow solver to study the nonequilibrium phenomena encountered in the
gas during a hyperbolic reentry into Earth's atmosphere. The analysis of the
populations of the rovibrational levels demonstrates how rotational and
vibrational relaxation proceed at the same rate. This contrasts with the common
misconception that translational and rotational relaxation occur concurrently. A
significant part of the relaxation process occurs in non-quasi-steady-state
conditions. Exchange processes are found to have a significant impact on the
relaxation of the gas, while predissociation has a negligible effect. The results
obtained by means of the full rovibrational collisional model are used to assess
the validity of reduced order models (vibrational collisional and
multitemperature) which are based on the same kinetic database. It is found that
thermalization and dissociation are drastically overestimated by the reduced
order models. The reasons of the failure differ in the two cases. In the
vibrational collisional model the overestimation of the dissociation is a
consequence of the assumption of equilibrium between the rotational energy and
the translational energy. The multitemperature model fails to predict the correct
thermochemical relaxation due to the failure of the quasi-steady-state
assumption, used to derive the phenomenological rate coefficient for
dissociation.
PMID- 25122372
TI - Hydrodynamic interaction of microswimmers near a wall.
AB - The hydrodynamics of an archetypal low-Reynolds number swimmer, called
"squirmer," near a wall has been numerically studied. For a single squirmer,
depending on the swimming mechanism, three different modes are distinguished: (a)
the squirmer escaping from the wall, (b) the squirmer swimming along the wall at
a constant distance and orientation angle, and (c) the squirmer swimming near the
wall in a periodic trajectory. The role of inertial effects on the near-wall
motion of the squirmer is quantified. The dynamics of multiple squirmers swimming
between two walls is found to be very different from a single squirmer. Near-wall
accumulation of squirmers are observed. At a relatively small concentration c =
0.1, around 60-80% of the squirmers are accumulated near the walls and attraction
of pushers and pullers toward the wall is stronger than neutral squirmers. Near
wall squirmers orient normal to the wall, while in the bulk region, the squirmers
are mostly oriented parallel to the wall. At a high concentration c = 0.4, the
percentage of the near-wall squirmers is around 40%. The orientation angle of
squirmers in the bulk region is more uniformly distributed at high
concentrations. In the near-wall region, pullers repel each other, while pushers
are attracted to each other and form clusters.
PMID- 25122373
TI - Spanwise gradients in flow speed help stabilize leading-edge vortices on
revolving wings.
AB - While a leading-edge vortex on an infinite translating wing is shed after a short
distance of travel, its counterpart on a finite span revolving insect wing or
maple seed membrane exhibits robust attachment. The latter explains the
aerodynamic lift generated by such biological species. Here we analyze the
mechanisms responsible for leading-edge vortex attachment. We compute the Navier
Stokes solution of the flow past a finite span wing (i) embedded in a uniform
oncoming flow, (ii) embedded in a spanwise varying oncoming flow, and (iii)
revolving about its root. We show that over flapping amplitudes typical of insect
flight (phi = 120 degrees ), the spanwise gradient of the local wing speed may
suffice in maintaining leading-edge vortex attachment. We correlate this result
with the development of spanwise flow, driven by the spanwise gradient of
pressure, and we evaluate the sensitivity of such a mechanism to the Reynolds
number. It is noted, however, that leading-edge vortex attachment through the
spanwise gradient of the local wing speed does not promote large lift, which
ultimately arises from centrifugal and Coriolis effects.
PMID- 25122374
TI - Simple model of a planar undulating magnetic microswimmer.
AB - One of the most efficient actuation methods of robotic microswimmers for
biomedical applications is by applying time-varying external magnetic fields. In
order to improve the design of the swimmer and optimize its performance, one
needs to develop simple theoretical models that enable explicit analysis of the
swimmer's dynamics. This paper studies the dynamics of a simple microswimmer
model with two magnetized links connected by an elastic joint, which undergoes
planar undulations induced by an oscillating magnetic field. The nonlinear
dynamics of the microswimmer is formulated by assuming Stokes flow and using
resistive force theory to calculate the viscous drag forces. Key effects that
enable the swimmer to overcome the scallop theorem and generate net propulsion
are identified, including violation of front-back symmetry. Assuming small
oscillation amplitude, approximate solution is derived by using perturbation
expansion, and leading-order expressions for the swimmer's displacement per cycle
X and average speed V are obtained. Optimal actuation frequencies that maximize X
or V are found for given swimmer's parameters. An ultimate optimal choice of
swimmer's parameters and actuation frequency is found, for which the average
swimming speed V attains a global maximum. Finally, the theoretical predictions
of optimal performance values are validated by comparison to reported
experimental results of magnetic microswimmers.
PMID- 25122375
TI - Interfacial pattern formation in confined power-law fluids.
AB - The interfacial pattern formation problem in an injection-driven radial Hele-Shaw
flow is studied for the situation in which a Newtonian fluid of negligible
viscosity displaces a viscous non-Newtonian power-law fluid. By utilizing a Darcy
law-like formulation, we tackle the fluid-fluid interface evolution problem
perturbatively, and we derive second-order mode-coupling equations that describe
the time evolution of the perturbation amplitudes. This allows us to investigate
analytically how the non-Newtonian nature of the dislocated fluid determines the
morphology of the emerging interfacial patterns. If the pushed fluid is shear
thinning, our results indicate the development of side-branching structures. On
the other hand, if the displaced fluid is shear-thickening, one detects the
formation of petal-like shapes, markedly characterized by strong tip-splitting
events. Finally, a time-dependent injection protocol is presented that is able to
restrain finger proliferation via side-branching and tip-splitting. This permits
the emergence of symmetric n-fold interfacial shapes for which the number of
fingers remains fixed as time progresses. This procedure generalizes existing
controlling strategies for purely Newtonian flow circumstances to the case of a
non-Newtonian, displaced power-law fluid.
PMID- 25122376
TI - Dynamics of the vapor layer below a Leidenfrost drop.
AB - In the Leidenfrost effect a small drop of fluid is levitated, above a
sufficiently hot surface, on a persistent vapor layer generated by evaporation
from the drop. The vapor layer thermally insulates the drop from the surface
leading to extraordinarily long drop lifetimes. The top-view shape of the
levitated drops can exhibit persistent starlike vibrations. I extend recent work
[Burton et al., Phys. Rev. Lett. 109, 074301 (2012)] to study the bottom surface
of the drop using interference imaging. In this work I use a high-speed camera
and automated image analysis to image, locate, and classify the interference
fringes. From the interference fringes I reconstruct the shape and height profile
of the rim where the drop is closest to the surface. I measure the drop-size
dependence of the planar vibrational mode frequencies, which agree well with
previous work. I observe a distinct breathing mode in the average radius of the
drop, the frequency of which scales differently with drop size than the other
modes. This breathing mode can be tightly coupled to a vertical motion of the
drop. I further observe a qualitative difference in the structure and dynamics of
the vertical profile of the rim between large and small drops.
PMID- 25122377
TI - Dynamics of an axisymmetric liquid bridge close to the minimum-volume stability
limit.
AB - We analyze both theoretically and experimentally the dynamical behavior of an
isothermal axisymmetric liquid bridge close to the minimum-volume stability
limit. First, the nature of this stability limit is investigated experimentally
by determining the liquid bridge response to a mass force pulse for volumes just
above that limit. In our experiments, the liquid bridge breakup takes place only
when the critical volume is surpassed and is never triggered by the mass force
pulse. Second, the growth of the small-amplitude perturbation mode initiating the
liquid bridge breakage is measured experimentally and calculated from the
linearized Navier-Stokes equations. The results of the linear stability analysis
allow one to explain why liquid bridges with volumes just above the stability
limit are so robust. Finally, the nonlinear process leading to the liquid bridge
breakup is described from both experimental data and the solution of the full
Navier-Stokes equations. Special attention is paid to the free-surface pinchoff.
The results show that the flow becomes universal (independent of both the initial
and boundary conditions) sufficiently close to that singularity and suggest that
the transition from the inviscid to the viscous regime is about to take place in
the final stage of both the experiments and numerical simulations.
PMID- 25122378
TI - Lattice model for spontaneous imbibition in porous media: the role of effective
tension and universality class.
AB - Recently, anomalous scaling properties of front broadening during spontaneous
imbibition of water in Vycor glass, a nanoporous medium, were reported: the mean
height and the width of the propagating front increase with time t both
proportional to t(1/2). Here, we propose a simple lattice imbibition model and
elucidate quantitatively how the correlation range of the hydrostatic pressure
and the disorder strength of the pore radii affect the scaling properties of the
imbibition front. We introduce an effective tension of liquid across neighboring
pores, which depends on the aspect ratio of each pore, and show that it leads to
a dynamical crossover: both the mean height and the roughness grow faster in the
presence of tension in the intermediate-time regime but eventually saturate in
the long-time regime. The universality class of the long-time behavior is
discussed by examining the associated scaling exponents and their relation to
directed percolation.
PMID- 25122379
TI - Effect of velocity boundary conditions on the heat transfer and flow topology in
two-dimensional Rayleigh-Benard convection.
AB - The effect of various velocity boundary condition is studied in two-dimensional
Rayleigh-Benard convection. Combinations of no-slip, stress-free, and periodic
boundary conditions are used on both the sidewalls and the horizontal plates. For
the studied Rayleigh numbers Ra between 10(8) and 10(11) the heat transport is
lower for Gamma=0.33 than for Gamma=1 in case of no-slip sidewalls. This is,
surprisingly, the opposite for stress-free sidewalls, where the heat transport
increases for a lower aspect ratio. In wider cells the aspect-ratio dependence is
observed to disappear for Ra >= 10(10). Two distinct flow types with very
different dynamics can be seen, mostly dependent on the plate velocity boundary
condition, namely roll-like flow and zonal flow, which have a substantial effect
on the dynamics and heat transport in the system. The predominantly horizontal
zonal flow suppresses heat flux and is observed for stress-free and asymmetric
plates. Low aspect-ratio periodic sidewall simulations with a no-slip boundary
condition on the plates also exhibit zonal flow. In all the other cases, the flow
is roll like. In two-dimensional Rayleigh-Benard convection, the velocity
boundary conditions thus have large implications on both roll-like and zonal flow
that have to be taken into consideration before the boundary conditions are
imposed.
PMID- 25122380
TI - Statistics of the inverse-cascade regime in two-dimensional magnetohydrodynamic
turbulence.
AB - We present a detailed direct numerical simulation of statistically steady,
homogeneous, isotropic, two-dimensional magnetohydrodynamic turbulence. Our study
concentrates on the inverse cascade of the magnetic vector potential. We examine
the dependence of the statistical properties of such turbulence on dissipation
and friction coefficients. We extend earlier work significantly by calculating
fluid and magnetic spectra, probability distribution functions (PDFs) of the
velocity, magnetic, vorticity, current, stream-function, and magnetic-vector
potential fields, and their increments. We quantify the deviations of these PDFs
from Gaussian ones by computing their flatnesses and hyperflatnesses. We also
present PDFs of the Okubo-Weiss parameter, which distinguishes between vortical
and extensional flow regions, and its magnetic analog. We show that the
hyperflatnesses of PDFs of the increments of the stream function and the magnetic
vector potential exhibit significant scale dependence and we examine the
implication of this for the multiscaling of structure functions. We compare our
results with those of earlier studies.
PMID- 25122381
TI - Casimir effect in active matter systems.
AB - We numerically examine run-and-tumble active matter particles in Casimir
geometries composed of two finite parallel walls. We find that there is an
attractive force between the two walls of a magnitude that increases with
increasing run length. The attraction exhibits an unusual exponential dependence
on the wall separation, and it arises due to a depletion of swimmers in the
region between the walls by a combination of the motion of the particles along
the walls and a geometric shadowing effect. This attraction is robust as long as
the wall length is comparable to or smaller than the swimmer run length, and is
only slightly reduced by the inclusion of steric interactions between swimmers.
We also examine other geometries and find regimes in which there is a crossover
from attraction to repulsion between the walls as a function of wall separation
and wall length.
PMID- 25122382
TI - Motion transitions of falling plates via quasisteady aerodynamics.
AB - In this paper, we study the dynamics of freely falling plates based on the
Kirchhoff equation and the quasisteady aerodynamic model. Motion transitions
among fluttering, tumbling along a cusp-like trajectory, irregular, and tumbling
along a straight trajectory are obtained by solving the dynamical equations.
Phase diagrams spanning between the nondimensional moment of inertia and
aerodynamic coefficients or aspect ratio are built to identify regimes for these
falling styles. We also investigate the stability of fixed points and bifurcation
scenarios. It is found that the transitions are all heteroclinic bifurcations and
the influence of the fixed-point stability is local.
PMID- 25122383
TI - Diffuse-interface modeling of liquid-vapor coexistence in equilibrium drops using
smoothed particle hydrodynamics.
AB - We study numerically liquid-vapor phase separation in two-dimensional,
nonisothermal, van der Waals (vdW) liquid drops using the method of smoothed
particle hydrodynamics (SPH). In contrast to previous SPH simulations of drop
formation, our approach is fully adaptive and follows the diffuse-interface model
for a single-component fluid, where a reversible, capillary (Korteweg) force is
added to the equations of motion to model the rapid but smooth transition of
physical quantities through the interface separating the bulk phases. Surface
tension arises naturally from the cohesive part of the vdW equation of state and
the capillary forces. The drop models all start from a square-shaped liquid and
spinodal decomposition is investigated for a range of initial densities and
temperatures. The simulations predict the formation of stable, subcritical liquid
drops with a vapor atmosphere, with the densities and temperatures of coexisting
liquid and vapor in the vdW phase diagram closely matching the binodal curve. We
find that the values of surface tension, as determined from the Young-Laplace
equation, are in good agreement with the results of independent numerical
simulations and experimental data. The models also predict the increase of the
vapor pressure with temperature and the fitting to the numerical data reproduces
very well the Clausius-Clapeyron relation, thus allowing for the calculation of
the vaporization pressure for this vdW fluid.
PMID- 25122384
TI - Statistical symmetries of the Lundgren-Monin-Novikov hierarchy.
AB - It was shown by Oberlack and Rosteck [Discr. Cont. Dyn. Sys. S, 3, 451 2010] that
the infinite set of multipoint correlation (MPC) equations of turbulence admits a
considerable extended set of Lie point symmetries compared to the Galilean group,
which is implied by the original set of equations of fluid mechanics.
Specifically, a new scaling group and an infinite set of translational groups of
all multipoint correlation tensors have been discovered. These new statistical
groups have important consequences for our understanding of turbulent scaling
laws as they are essential ingredients of, e.g., the logarithmic law of the wall
and other scaling laws, which in turn are exact solutions of the MPC equations.
In this paper we first show that the infinite set of translational groups of all
multipoint correlation tensors corresponds to an infinite dimensional set of
translations under which the Lundgren-Monin-Novikov (LMN) hierarchy of equations
for the probability density functions (PDF) are left invariant. Second, we derive
a symmetry for the LMN hierarchy which is analogous to the scaling group of the
MPC equations. Most importantly, we show that this symmetry is a measure of the
intermittency of the velocity signal and the transformed functions represent PDFs
of an intermittent (i.e., turbulent or nonturbulent) flow. Interesting enough,
the positivity of the PDF puts a constraint on the group parameters of both shape
and intermittency symmetry, leading to two conclusions. First, the latter
symmetries may no longer be Lie group as under certain conditions group
properties are violated, but still they are symmetries of the LMN equations.
Second, as the latter two symmetries in its MPC versions are ingredients of many
scaling laws such as the log law, the above constraints implicitly put weak
conditions on the scaling parameter such as von Karman constant kappa as they are
functions of the group parameters. Finally, let us note that these kind of
statistical symmetries are of much more general type, i.e., not limited to MPC or
PDF equations emerging from Navier-Stokes, but instead they are admitted by other
nonlinear partial differential equations like, for example, the Burgers equation
when in conservative form and if the nonlinearity is quadratic.
PMID- 25122385
TI - Humidity distribution affected by freely exposed water surfaces: simulations and
experimental verification.
AB - Accurate models for the water vapor flux at a water-air interface are required in
various scientific, reliability and civil engineering aspects. Here, a study of
humidity distribution in a container with air and freely exposed water is
presented. A model predicting a spatial distribution and time evolution of
relative humidity based on statistical rate theory and computational fluid
dynamics is developed. In our approach we use short-term steady-state steps to
simulate the slowly evolving evaporation in the system. Experiments demonstrate
considerably good agreement with the computer modeling and allow one to
distinguish the most important parameters for the model.
PMID- 25122386
TI - Casimir effect in swimmer suspensions.
AB - We show that the Casimir effect can emerge in microswimmer suspensions. In
principle, two effects conspire against the development of Casimir effects in
swimmer suspensions. First, at low Reynolds number, the force on any closed
volume vanishes, but here the relevant effect is the drag by the flow produced by
the swimmers, which can be finite. Second, the fluid velocity and the pressure
are linear on the swimmer force dipoles, and averaging over the swimmer
orientations would lead to a vanishing effect. However, being that the suspension
is a discrete system, the noise terms of the coarse-grained equations depend on
the density, which itself fluctuates, resulting in effective nonlinear dynamics.
Applying the tools developed for other nonequilibrium systems to general coarse
grained equations for swimmer suspensions, the Casimir drag is computed on
immersed objects, and it is found to depend on the correlation function between
the rescaled density and dipolar density fields. By introducing a model
correlation function with medium-range order, explicit expressions are obtained
for the Casimir drag on a body. When the correlation length is much larger than
the microscopic cutoff, the average drag is independent of the correlation
length, with a range that depends only on the size of the immersed bodies.
PMID- 25122387
TI - Geometrical interpretation of long-time tails of first-passage time distributions
in porous media with stagnant parts.
AB - Using a combined experimental-numerical approach, we study the first-passage time
distributions (FPTD) of small particles in two-dimensional porous materials. The
distributions in low-porosity structures show persistent long-time tails, which
are independent of the Peclet number and therefore cannot be explained by the
advection-diffusion equation. Instead, our results suggest that these tails are
caused by stagnant, i.e., quiescent areas where particles are trapped for some
time. Comparison of measured FPTD with an analytical expression for the residence
time of particles, which diffuse in confined regions and are able to escape
through a small pore, yields good agreement with our data.
PMID- 25122388
TI - Saturation of shape instabilities in single-bubble sonoluminescence.
AB - Excitation of shape instabilities represents one route to bubble death in single
bubble sonoluminescence. This feature is satisfactorily explained by an expansion
to first order in the amplitude of a shape distortion in the form of a spherical
harmonic. By taking the expansion to second order, it is found that regions of
parameter space exist where the exponential growth into bubble disruption is
checked and a saturated stable state of shape distortion is possible.
Experimental evidence provided by Mie scattering is presented, and a possible
connection to simultaneous spatially anisotropic light emission is discussed.
PMID- 25122389
TI - Chaotic mixing in effective compressible flows.
AB - We study numerically joint mixing of salt and colloids by chaotic advection and
how salt inhomogeneities accelerate or delay colloid mixing by inducing a
velocity drift V(dp) between colloids and fluid particles as proposed in recent
experiments [J. Deseigne et al., Soft Matter 10, 4795 (2014)]. We demonstrate
that because the drift velocity is no longer divergence free, small variations to
the total velocity field drastically affect the evolution of colloid variance
sigma(2) = -(2). A consequence is that mixing strongly depends on the
mutual coherence between colloid and salt concentration fields, the short time
evolution of scalar variance being governed by a new variance production term P =
-/2 when scalar gradients are not developed yet so that
dissipation is weak. Depending on initial conditions, mixing is then delayed or
enhanced, and it is possible to find examples for which the two regimes (fast
mixing followed by slow mixing) are observed consecutively when the variance
source term reverses its sign. This is indeed the case for localized patches
modeled as Gaussian concentration profiles.
PMID- 25122390
TI - Extension of the dielectric breakdown model for simulation of viscous fingering
at finite viscosity ratios.
AB - Immiscible displacement of viscous oil by water in a petroleum reservoir is often
hydrodynamically unstable. Due to similarities between the physics of dielectric
breakdown and immiscible flow in porous media, we extend the existing dielectric
breakdown model to simulate viscous fingering patterns for a wide range of
viscosity ratios (MU(r)). At low values of power-law index eta, the system
behaves like a stable Eden growth model and as the value of eta is increased to
unity, diffusion limited aggregation-like fractals appear. This model is compared
with our two-dimensional (2D) experiments to develop a correlation between the
viscosity ratio and the power index, i.e., eta = 10(-5)MU(r)(0.8775). The 2D and
three-dimensional (3D) simulation data appear scalable. The fingering pattern in
3D simulations at finite viscosity ratios appear qualitatively similar to the few
experimental results published in the literature.
PMID- 25122391
TI - Taylor column instability in the problem of a vibrational hydrodynamic top.
AB - The object of experimental study is a fluid flow generated by differential
rotation of a free light spherical body in a rotating cylindrical cavity. The
body stays near the axis under the action of centrifugal force. The body rotation
is generated by a force field oscillating in the cavity reference system
(vibrational hydrodynamic top). It was found that the Taylor-Proudman column that
forms undergoes instability, which manifests itself in the formation of a two
dimensional azimuthal wave at the column boundary, in a Stewartson layer. The
experimental results are summarized on a plane of dimensionless parameters, i.e.,
the dimensionless velocity of the cavity rotation and Rossby number. The bounds
of the Stewartson layer stability were found and the supercritical structures and
transition sequences were studied. Systematic research into that problem in its
classical formulation--when a sphere is fixed on the axis and its differential
rotation is imposed--was done for comparison. It was demonstrated that in
conditions of vibratory differential rotation of a free sphere the stability
threshold of the Stewartson layer was reduced by more than one order of
magnitude, in comparison with the classical case. A qualitative change was also
found in the wave phase velocity which for a free sphere exceeds the lagging
differential rotation velocity of the body. It was concluded that the uncovered
specifics are related to the difference in the mechanism of the Taylor-Proudman
column formation and of the flow generation in it. For a vibrational hydrodynamic
top, streams in the column will not be defined by Ekman pumping but by steady
streaming, which is also responsible for the free-sphere differential rotation.
PMID- 25122392
TI - Dynamics of a self-diffusiophoretic particle in shear flow.
AB - Colloidal particles can achieve autonomous motion by a number of physicochemical
mechanisms. For instance, if a spherical particle acts as a catalyst with an
asymmetric surface reactivity, a molecular solute concentration gradient will
develop in the surrounding fluid that can propel the particle via self
diffusiophoresis. Theoretical analyses of self-diffusiophoresis have mostly been
considered in quiescent fluid, where the solute concentration is usually assumed
to evolve solely via diffusion. In practical applications, however, self
propelled colloidal particles can be expected to reside in flowing fluids. Here,
we examine the role of ambient flow on self-diffusiophoresis by quantifying the
dynamics of a model Janus particle in a simple shear flow. The imposed flow can
distort the self-generated solute concentration gradient. The extent of this
distortion is quantified by a Peclet number, Pe, associated with the shear flow.
Utilizing matched asymptotic analysis, we determine the concentration gradient
surrounding a Janus particle in shear flow at a small, but finite, Peclet number
and the resulting particle motion. For example, when the symmetry axis of the
particle is aligned with the imposed flow, the Janus particle experiences an
O(Pe) cross-streamline drift and an O(Pe(3/2)) reduction in translational
velocity along the flow direction. We then analyze the in-plane trajectory of the
Janus particle in shear. We find that the particle performs elliptical orbits
around its initial position in the flow, which decrease in size with increasing
Pe.
PMID- 25122393
TI - Three-dimensional coherent structures of electrokinetic instability.
AB - A direct numerical simulation of the three-dimensional elektrokinetic instability
near a charge-selective surface (electric membrane, electrode, or system of micro
or nanochannels) has been carried out and analyzed. A special finite-difference
method has been used for the space discretization along with a semi-implicit 31/3
step Runge-Kutta scheme for the integration in time. The calculations employ
parallel computing. Three characteristic patterns, which correspond to the
overlimiting currents, are observed: (a) two-dimensional electroconvective rolls,
(b) three-dimensional regular hexagonal structures, and (c) three-dimensional
structures of spatiotemporal chaos, which are a combination of unsteady hexagons,
quadrangles, and triangles. The transition from (b) to (c) is accompanied by the
generation of interacting two-dimensional solitary pulses.
PMID- 25122394
TI - Pore-scale simulation of fluid flow and solute dispersion in three-dimensional
porous media.
AB - In the present work fluid flow and solute transport through porous media are
described by solving the governing equations at the pore scale with finite-volume
discretization. Instead of solving the simplified Stokes equation (very often
employed in this context) the full Navier-Stokes equation is used here. The
realistic three-dimensional porous medium is created in this work by packing
together, with standard ballistic physics, irregular and polydisperse objects.
Emphasis is placed on numerical issues related to mesh generation and spatial
discretization, which play an important role in determining the final accuracy of
the finite-volume scheme and are often overlooked. The simulations performed are
then analyzed in terms of velocity distributions and dispersion rates in a wider
range of operating conditions, when compared with other works carried out by
solving the Stokes equation. Results show that dispersion within the analyzed
porous medium is adequately described by classical power laws obtained by
analytic homogenization. Eventually the validity of Fickian diffusion to treat
dispersion in porous media is also assessed.
PMID- 25122395
TI - Asymptotic separation in multispecies collisional plasma shocks.
AB - When a piston drives a shock in a multicomponent plasma, residual separation of
the ion species persists close to the piston-plasma boundary, long after the
shock has propagated away from the boundary and has reached a (nearly) steady
state solution. This effect is observed in hybrid particle-in-cell simulations
with two kinetic ion species and fluid electrons. It is a consequence of the
different dynamics experienced by ions of different mass and charge-to-mass ratio
and must be taken into account to properly model the physics of species
separation in collisional plasma shocks.
PMID- 25122396
TI - Experimental measurement of velocity correlations for two microparticles in a
plasma with ion flow.
AB - Velocity correlations are measured in a dusty plasma with only two
microparticles. These correlations allow a characterization of the oscillatory
modes and an identification of the effects of ion wakes. Ion wake effects are
isolated by comparing two experiments with the microparticles aligned parallel vs
perpendicular to the ion flow. From records of microparticle velocities, the one-
and two-particle distribution functions f(1) and f(2) are obtained, and the two
particle correlation function g(2) = f(2)-f(1)f(1) is calculated. Comparing the
two experiments, we find that motion is much more correlated when the
microparticles are aligned with the ion flow and the character of the oscillatory
modes depends on the ion flow direction due to the ion wake.
PMID- 25122397
TI - Quantum-relativistic hydrodynamic model for a spin-polarized electron gas
interacting with light.
AB - We develop a semirelativistic quantum fluid theory based on the expansion of the
Dirac Hamiltonian to second order in 1/c. By making use of the Madelung
representation of the wave function, we derive a set of hydrodynamic equations
that comprises a continuity equation, an Euler equation for the mean velocity,
and an evolution equation for the electron spin density. This hydrodynamic model
is then applied to study the dynamics of a dense and weakly relativistic electron
plasma. In particular, we investigate the impact of the quantum-relativistic spin
effects on the Faraday rotation in a one-dimensional plasma slab irradiated by an
x-ray laser source.
PMID- 25122399
TI - Superdiffusion of two-dimensional Yukawa liquids due to a perpendicular magnetic
field.
AB - Stochastic transport of a two-dimensional (2D) dusty plasma liquid with a
perpendicular magnetic field is studied. Superdiffusion is found to occur
especially at higher magnetic fields with beta of order unity. Here, beta =
omega(c)/omega(pd) is the ratio of the cyclotron and plasma frequencies for dust
particles. The mean-square displacement MSD = 4D(alpha)t(alpha) is found to have
an exponent alpha > 1, indicating superdiffusion, with alpha increasing
monotonically to 1.1 as beta increases to unity. The 2D Langevin molecular
dynamics simulation used here also reveals that another indicator of random
particle motion, the velocity autocorrelation function, has a dominant peak
frequency omega(peak) that empirically obeys omega(peak)(2) = omega(c)(2) +
omega(pd)(2)/4.
PMID- 25122401
TI - Interaction force in a vertical dust chain inside a glass box.
AB - Small number dust particle clusters can be used as probes for plasma diagnostics.
The number of dust particles as well as cluster size and shape can be easily
controlled employing a glass box placed within a Gaseous Electronics Conference
(GEC) rf reference chamber to provide confinement of the dust. The plasma
parameters inside this box and within the larger plasma chamber have not yet been
adequately defined. Adjusting the rf power alters the plasma conditions causing
structural changes of the cluster. This effect can be used to probe the
relationship between the rf power and other plasma parameters. This experiment
employs the sloshing and breathing modes of small cluster oscillations to examine
the relationship between system rf power and the particle charge and plasma
screening length inside the glass box. The experimental results provided indicate
that both the screening length and dust charge decrease as rf power inside the
box increases. The decrease in dust charge as power increases may indicate that
ion trapping plays a significant role in the sheath.
PMID- 25122400
TI - Observation of self-excited acoustic vortices in defect-mediated dust acoustic
wave turbulence.
AB - Using the self-excited dust acoustic wave as a platform, we demonstrate
experimental observation of self-excited fluctuating acoustic vortex pairs with
+/- 1 topological charges through spontaneous waveform undulation in defect
mediated turbulence for three-dimensional traveling nonlinear longitudinal waves.
The acoustic vortex pair has helical waveforms with opposite chirality around the
low-density hole filament pair in xyt space (the xy plane is the plane normal to
the wave propagation direction). It is generated through ruptures of sequential
crest surfaces and reconnections with their trailing ruptured crest surfaces. The
initial rupture is originated from the amplitude reduction induced by the
formation of the kinked wave crest strip with strong stretching through the
undulation instability. Increasing rupture causes the separation of the acoustic
vortex pair after generation. A similar reverse process is followed for the
acoustic vortex annihilating with the opposite-charged acoustic vortex from the
same or another pair generation.
PMID- 25122402
TI - Role of viscous friction in the reverse rotation of a disk.
AB - The mechanical response of a circularly driven disk in a dissipative medium is
considered. We focus on the role played by viscous friction in the spinning
motion of the disk, especially on the effect called reverse rotation, where the
intrinsic and orbital rotations are antiparallel. Contrary to what happens in the
frictionless case, where steady reverse rotations are possible, we find that this
dynamical behavior may exist only as a transient when dissipation is considered.
Whether or not reverse rotations in fact occur depends on the initial conditions
and on two parameters, one related to dragging, inertia, and driving, the other
associated with the geometric configuration of the system. The critical value of
this geometric parameter (separating the regions where reverse rotation is
possible from those where it is forbidden) as a function of viscosity is well
adjusted by a q-exponential function.
PMID- 25122398
TI - Equilibration dynamics and conductivity of warm dense hydrogen.
AB - We investigate subpicosecond dynamics of warm dense hydrogen at the XUV free
electron laser facility (FLASH) at DESY (Hamburg). Ultrafast impulsive electron
heating is initiated by a <= 300-fs short x-ray burst of 92-eV photon energy. A
second pulse probes the sample via x-ray scattering at jitter-free variable time
delay. We show that the initial molecular structure dissociates within (0.9 +/-
0.2) ps, allowing us to infer the energy transfer rate between electrons and
ions. We evaluate Saha and Thomas-Fermi ionization models in radiation
hydrodynamics simulations, predicting plasma parameters that are subsequently
used to calculate the static structure factor. A conductivity model for partially
ionized plasma is validated by two-temperature density-functional theory coupled
to molecular dynamic simulations and agrees with the experimental data. Our
results provide important insights and the needed experimental data on transport
properties of dense plasmas.
PMID- 25122403
TI - Self-similar propagation and asymptotic optical waves in nonlinear waveguides.
AB - The properties of self-similar optical waves propagating in a tapered cubic
quintic nonlinear waveguide are investigated. Using a lens-type transformation we
obtain the exact analytical self-similar solutions which describe the propagation
of bright-shaped solitons, dark-shaped solitons, kink-shaped solitons, and
antikink-shaped solitons. The stability of the solutions is examined by numerical
simulations such that stable bright solitons are found. Beyond the exact
analytical solutions, asymptotic optical waves are also found by employing a
direct ansatz. These waves possess linear chirps and can propagate self
similarly. The possibility of controlling the shape of output asymptotic optical
waves is demonstrated. The analytical results are confirmed by numerical
simulations. Finally, we investigate the generation and propagation properties of
self-similar optical waves in a quintic nonlinear medium.
PMID- 25122404
TI - Improved transfer matrix methods for calculating quantum transmission
coefficient.
AB - Methods for calculating the transmission coefficient are proposed, all of which
arise from improved nonreflecting WKB boundary conditions at the edge of the
computational domain in one-dimensional geometries. In the first, the Schrodinger
equation is solved numerically, while the second is a transfer matrix (TM)
algorithm where the potential is approximated by steps, but with the first and
last matrix modified to reflect the new boundary condition. Both methods give
excellent results with first-order WKB boundary conditions. The third uses the
transfer matrix method with third-order WKB boundary conditions. For the
parabolic potential, the average error for the modified third-order TM method
reduces by factor of 4100 over the unmodified TM method.
PMID- 25122405
TI - Theory of ion transport with fast acid-base equilibrations in bioelectrochemical
systems.
AB - Bioelectrochemical systems recover valuable components and energy in the form of
hydrogen or electricity from aqueous organic streams. We derive a one-dimensional
steady-state model for ion transport in a bioelectrochemical system, with the
ions subject to diffusional and electrical forces. Since most of the ionic
species can undergo acid-base reactions, ion transport is combined in our model
with infinitely fast ion acid-base equilibrations. The model describes the
current-induced ammonia evaporation and recovery at the cathode side of a
bioelectrochemical system that runs on an organic stream containing ammonium
ions. We identify that the rate of ammonia evaporation depends not only on the
current but also on the flow rate of gas in the cathode chamber, the diffusion of
ammonia from the cathode back into the anode chamber, through the ion exchange
membrane placed in between, and the membrane charge density.
PMID- 25122406
TI - Boundary condition at a two-phase interface in the lattice Boltzmann method for
the convection-diffusion equation.
AB - A boundary scheme in the lattice Boltzmann method (LBM) for the convection
diffusion equation, which correctly realizes the internal boundary condition at
the interface between two phases with different transport properties, is
presented. The difficulty in satisfying the continuity of flux at the interface
in a transient analysis, which is inherent in the conventional LBM, is overcome
by modifying the collision operator and the streaming process of the LBM. An
asymptotic analysis of the scheme is carried out in order to clarify the role
played by the adjustable parameters involved in the scheme. As a result, the
internal boundary condition is shown to be satisfied with second-order accuracy
with respect to the lattice interval, if we assign appropriate values to the
adjustable parameters. In addition, two specific problems are numerically
analyzed, and comparison with the analytical solutions of the problems
numerically validates the proposed scheme.
PMID- 25122407
TI - Multiscale dynamics of semiflexible polymers from a universal coarse-graining
procedure.
AB - Simulating the dynamics of a semiflexible polymer across time and length scales
that bridge the rigid and flexible regimes requires a physically sound method for
generating coarse-grained representations of the polymer. Here, we study the
dynamic behavior of the discrete stretchable, shearable wormlike chain model,
which can be used to coarse-grain a continuous semi-elastic chain at an arbitrary
discretization. We show that the dynamics of this universal model match those of
the wormlike chain at length scales above the discretization length. The
evolution of the stress correlation, as probed through Brownian dynamics
simulations, is found to reproduce the predicted behavior in both the rigid and
flexible regimes, spanning over six orders of magnitude in time scales. The
coarse-graining approach employed here thus enables dynamic simulation of
semiflexible polymers at lengths and times that were previously inaccessible with
conventional methods.
PMID- 25122408
TI - Nonequilibrium scheme for computing the flux of the convection-diffusion equation
in the framework of the lattice Boltzmann method.
AB - In this paper, we propose a local nonequilibrium scheme for computing the flux of
the convection-diffusion equation with a source term in the framework of the
multiple-relaxation-time (MRT) lattice Boltzmann method (LBM). Both the Chapman
Enskog analysis and the numerical results show that, at the diffusive scaling,
the present nonequilibrium scheme has a second-order convergence rate in space. A
comparison between the nonequilibrium scheme and the conventional second-order
central-difference scheme indicates that, although both schemes have a second
order convergence rate in space, the present nonequilibrium scheme is more
accurate than the central-difference scheme. In addition, the flux computation
rendered by the present scheme also preserves the parallel computation feature of
the LBM, making the scheme more efficient than conventional finite-difference
schemes in the study of large-scale problems. Finally, a comparison between the
single-relaxation-time model and the MRT model is also conducted, and the results
show that the MRT model is more accurate than the single-relaxation-time model,
both in solving the convection-diffusion equation and in computing the flux.
PMID- 25122409
TI - Real-space finite-difference calculation method of generalized Bloch wave
functions and complex band structures with reduced computational cost.
AB - Generalized Bloch wave functions of bulk structures, which are composed of not
only propagating waves but also decaying and growing evanescent waves, are known
to be essential for defining the open boundary conditions in the calculations of
the electronic surface states and scattering wave functions of surface and
junction structures. Electronic complex band structures being derived from the
generalized Bloch wave functions are also essential for studying bound states of
the surface and junction structures, which do not appear in conventional band
structures. We present a novel calculation method to obtain the generalized Bloch
wave functions of periodic bulk structures by solving a generalized eigenvalue
problem, whose dimension is drastically reduced in comparison with the
conventional generalized eigenvalue problem derived by Fujimoto and Hirose [Phys.
Rev. B 67, 195315 (2003)]. The generalized eigenvalue problem derived in this
work is even mathematically equivalent to the conventional one, and, thus, we
reduce computational cost for solving the eigenvalue problem considerably without
any approximation and losing the strictness of the formulations. To exhibit the
performance of the present method, we demonstrate practical calculations of
electronic complex band structures and electron transport properties of Al and Cu
nanoscale systems. Moreover, employing atom-structured electrodes and jellium
approximated ones for both of the Al and Si monatomic chains, we investigate how
much the electron transport properties are unphysically affected by the jellium
parts.
PMID- 25122410
TI - Self-energy-modified Poisson-Nernst-Planck equations: WKB approximation and
finite-difference approaches.
AB - We propose a modified Poisson-Nernst-Planck (PNP) model to investigate charge
transport in electrolytes of inhomogeneous dielectric environment. The model
includes the ionic polarization due to the dielectric inhomogeneity and the ion
ion correlation. This is achieved by the self energy of test ions through solving
a generalized Debye-Huckel (DH) equation. We develop numerical methods for the
system composed of the PNP and DH equations. Particularly, toward the numerical
challenge of solving the high-dimensional DH equation, we developed an analytical
WKB approximation and a numerical approach based on the selective inversion of
sparse matrices. The model and numerical methods are validated by simulating the
charge diffusion in electrolytes between two electrodes, for which effects of
dielectrics and correlation are investigated by comparing the results with the
prediction by the classical PNP theory. We find that, at the length scale of the
interface separation comparable to the Bjerrum length, the results of the
modified equations are significantly different from the classical PNP predictions
mostly due to the dielectric effect. It is also shown that when the ion self
energy is in weak or mediate strength, the WKB approximation presents a high
accuracy, compared to precise finite-difference results.
PMID- 25122411
TI - Path-integral Monte Carlo method for Renyi entanglement entropies.
AB - We introduce a quantum Monte Carlo algorithm to measure the Renyi entanglement
entropies in systems of interacting bosons in the continuum. This approach is
based on a path-integral ground state method that can be applied to interacting
itinerant bosons in any spatial dimension with direct relevance to experimental
systems of quantum fluids. We demonstrate how it may be used to compute spatial
mode entanglement, particle partitioned entanglement, and the entanglement of
particles, providing insights into quantum correlations generated by
fluctuations, indistinguishability, and interactions. We present proof-of
principle calculations and benchmark against an exactly soluble model of
interacting bosons in one spatial dimension. As this algorithm retains the
fundamental polynomial scaling of quantum Monte Carlo when applied to sign
problem-free models, future applications should allow for the study of
entanglement entropy in large-scale many-body systems of interacting bosons.
PMID- 25122412
TI - Generalized modification in the lattice Bhatnagar-Gross-Krook model for
incompressible Navier-Stokes equations and convection-diffusion equations.
AB - In this paper, two modified lattice Boltzmann Bhatnagar-Gross-Krook (LBGK) models
for incompressible Navier-Stokes equations and convection-diffusion equations are
proposed via the addition of correction terms in the evolution equations.
Utilizing this modification, the value of the dimensionless relaxation time in
the LBGK model can be kept in a proper range, and thus the stability of the LBGK
model can be improved. Although some gradient operators are included in the
correction terms, they can be computed efficiently using local computational
schemes such that the present LBGK models still retain the intrinsic parallelism
characteristic of the lattice Boltzmann method. Numerical studies of the steady
Poiseuille flow and unsteady Womersley flow show that the modified LBGK model has
a second-order convergence rate in space, and the compressibility effect in the
common LBGK model can be eliminated. In addition, to test the stability of the
present models, we also performed some simulations of the natural convection in a
square cavity, and we found that the results agree well with those reported in
the previous work, even at a very high Rayleigh number (Ra = 10(12)).
PMID- 25122413
TI - Acoustic equations of state for simple lattice Boltzmann velocity sets.
AB - The lattice Boltzmann (LB) method typically uses an isothermal equation of state.
This is not sufficient to simulate a number of acoustic phenomena where the
equation of state cannot be approximated as linear and constant. However, it is
possible to implement variable equations of state by altering the LB equilibrium
distribution. For simple velocity sets with velocity components xi(ialpha)?(
1,0,1) for all i, these equilibria necessarily cause error terms in the momentum
equation. These error terms are shown to be either correctable or negligible at
the cost of further weakening the compressibility. For the D1Q3 velocity set,
such an equilibrium distribution is found and shown to be unique. Its sound
propagation properties are found for both forced and free waves, with some
generality beyond D1Q3. Finally, this equilibrium distribution is applied to a
nonlinear acoustics simulation where both mechanisms of nonlinearity are
simulated with good results. This represents an improvement on previous such
simulations and proves that the compressibility of the method is still
sufficiently strong even for nonlinear acoustics.
PMID- 25122414
TI - Electronically- and crystal-structure-driven magnetic structures and physical
properties of RScSb (R = rare earth) compounds: a neutron diffraction,
magnetization and heat capacity study.
AB - The synthesis of the new equiatomic RScSb (R = La-Nd, Sm, Gd-Tm, Lu, Y) compounds
has been recently reported. These rare earth compounds crystallize in two
different crystal structures, adopting the CeScSi-type (I4/mmm) for the lighter R
(La-Nd, Sm) and the CeFeSi-type (P4/nmm) structure for the heavier R (R = Gd-Tm,
Lu, Y). Here we report the results of neutron diffraction, magnetization and heat
capacity measurements on some of these compounds (R = Ce, Pr, Nd, Gd and Tb).
Band structure calculations have also been performed on CeScSb and GdScGe (CeScSi
type), and on GdScSb and TbScSb (CeFeSi-type) to compare and understand the
exchange interactions in CeScSi and CeFeSi structure types. The neutron
diffraction investigation shows that all five compounds order magnetically, with
the highest transition temperature of 66 K in TbScSb and the lowest of about 9 K
in CeScSb. The magnetic ground state is simple ferromagnetic (tau = [0 0 0]) in
CeScSb, as well in NdScSb for 32 > T > 22 K. Below 22 K a second magnetic
transition, with propagation vector tau = [1/4 1/4 0], appears in NdScSb. PrScSb
has a magnetic structure within, determined by mostly ferromagnetic interactions
and antiferromagnetic alignment of the Pr-sites connected through the I-centering
(tau = [1 0 0]). A cycloidal spiral structure with a temperature dependent
propagation vector tau = [delta delta 1/2] is found in TbScSb. The results of
magnetization and heat capacity lend support to the main conclusions derived from
neutron diffraction. As inferred from a sharp peak in magnetization, GdScSb
orders antiferromagnetically at 56 K. First principles calculations show lateral
shift of spin split bands towards lower energy from the Fermi level as the CeScSi
type structure changes to the CeFeSi-type structure. This rigid shift may force
the system to transform from exchange split ferromagnetic state to the
antiferromagnetic state in RScSb compounds (as seen for example in GdScSb and
TbScSb) and is proposed to explain the change-over from a ferromagnetic structure
as found in the CeScSi-type compounds CeScSb and NdScSb to the antiferromagnetic
state as found in TbScSb and GdScSb.
PMID- 25122417
TI - A note from the Editor-in-Chief on enhancements to the journal.
PMID- 25122415
TI - Construction and characterization of a repetitive DNA library in Parodontidae
(Atinopterygii:Characiformes): a genomic and evolutionary approach to the
degeneration of the w sex cromosome.
AB - Repetitive DNA sequences, including tandem and dispersed repeats, comprise a
large portion of eukaryotic genomes and are important for gene regulation, sex
chromosome differentiation, and karyotype evolution. In Parodontidae, only the
repetitive DNAs WAp and pPh2004 and rDNAs were previously studied using
fluorescence in situ hybridization. This study aimed to build a library of
repetitive DNA in Parodontidae. We isolated 40 clones using Cot-1; 17 of these
clones exhibited similarity to repetitive DNA sequences, including satellites,
minisatellites, microsatellites, and class I and class II transposable elements
(TEs), from Danio rerio and other organisms. The physical mapping of the clones
to chromosomes revealed the presence of a satellite DNA, a Helitron element, and
degenerate short interspersed element (SINE), long interspersed element (LINE),
and tc1-mariner elements on the sex chromosomes. Some clones exhibited dispersed
signals; other sequences were not detected. The 5S rDNA was detected on an
autosomal pair. These elements likely function in the molecular degeneration of
the W chromosome in Parodontidae. Thus, the location of these elements on the
chromosomes is important for understanding the function of these repetitive DNAs
and for integrative studies with genome sequencing. The presented data
demonstrate that an intensive invasion of TEs occurred during W sex chromosome
differentiation in the Parodontidae.
PMID- 25122418
TI - Practice makes perfect protocols: the Canadian anaplastic lymphoma kinase study.
PMID- 25122419
TI - RET mutations in neuroendocrine tumors: including small-cell lung cancer.
PMID- 25122420
TI - An evidence-based determination of issues affecting quality of life and patient
reported outcomes in lung cancer: results of a survey of 660 patients.
AB - INTRODUCTION: Identifying issues of importance for patients with lung cancer is
critical in individualizing care and developing effective quality of life
instruments based on evidence. This study was conducted to provide enhanced
content validity for measures assessing quality of life and patient-reported
outcomes (PROs). METHODS: We conducted an anonymous, cross-sectional, electronic
web-based survey of 660 lung cancer patients. The survey asked patients to rank
20 quality of life issues on a 5-point scale ranging from "not important at all"
to "very important". Analysis was obtained using key factors such as stage of
disease, performance status, and gender. RESULTS: The survey was completed by 297
males and 363 females (median age 62 years). The top five rated issues were:
quality of life, maintaining independence, ability to perform normal activities,
ability to sleep, and not being fatigued. The issues of importance were all
ranked, using the two highest categories ("very important" and "important") by at
least 90% of patients. Although symptoms are important to patients, they were not
the most highly ranked issues of concern; instead, global issues illustrating the
effect of the symptoms on the patient, such as quality of life, maintaining
independence, and performing normal activities were ranked highest. CONCLUSIONS:
This is the largest analysis of evidence-based data determining content validity
for quality of life and PROs as indicated by patients. These results provide
greater confidence that the content of lung cancer quality of life measures is
appropriate. In addition, the survey clearly demonstrates that PRO measures that
only evaluate symptoms are not fully responding to patient-expressed needs.
PMID- 25122421
TI - Association of patient-provider communication domains with lung cancer treatment.
AB - BACKGROUND: Patient-physician communication is critical for helping patients
understand and complete the complex steps needed to diagnose stage and treat lung
cancer. We assessed which domains of patient-physician communication about lung
cancer and its treatment are associated with receipt of disease-directed, stage
appropriate treatment. METHODS: Patients with recently diagnosed lung cancer were
recruited from four medical centers in New York City from 2008 to 2011.
Participants were surveyed about discussions with physicians regarding treatment,
symptoms, and needs. Multiple regression analysis and structural equation
modeling were used to assess which communication factors were associated with
disease treatment. RESULTS: Of the 352 participants, 191 (54%) received disease
directed, stage-appropriate treatment. Unadjusted associations between
communication items and treatment found that participants who felt that their
physicians explained the risks and disadvantages of lung cancer treatment (p <
0.01), discussed their chances of cure (p = 0.02), discussed goals of treatment
(p < 0.01), or who were warm and friendly (p = 0.04) were more likely to undergo
treatment. Three communication domains were identified: treatment information,
physician support, and patient symptoms/needs. After adjusting for known
determinants of lung cancer treatment, increased treatment information was
associated with higher probability of cancer-directed treatment (p = 0.003).
Other communication domains (physician support or patient symptoms/needs) were
not independent predictors of treatment (p > 0.05 for both comparisons).
CONCLUSION: These data suggest that treatment information is particularly
important for increasing the probability of cancer-directed therapy among lung
cancer patients. Clinicians should ensure that they clearly discuss treatment
goals and options with patients while maintaining empathy, supporting patient
needs, and addressing symptoms.
PMID- 25122422
TI - Canadian anaplastic lymphoma kinase study: a model for multicenter
standardization and optimization of ALK testing in lung cancer.
AB - INTRODUCTION: Fluorescence in situ hybridization (FISH) is currently the standard
for diagnosing anaplastic lymphoma kinase (ALK)-rearranged (ALK+) lung cancers
for ALK inhibitor therapies. ALK immunohistochemistry (IHC) may serve as a
screening and alternative diagnostic method. The Canadian ALK (CALK) study was
initiated to implement a multicenter optimization and standardization of
laboratory developed ALK IHC and FISH tests across 14 hospitals. METHODS: Twenty
eight lung adenocarcinomas with known ALK status were used as blinded study
samples. Thirteen laboratories performed IHC using locally developed staining
protocols for 5A4, ALK1, or D5F3 antibodies; results were assessed by H-score.
Twelve centers conducted FISH using protocols based on Vysis' ALK break-apart
FISH kit. Initial IHC results were used to optimize local IHC protocols, followed
by a repeat IHC study to assess the results of standardization. Three
laboratories conducted a prospective parallel IHC and FISH analysis on 411
consecutive clinical samples using post-validation optimized assays. RESULTS:
Among study samples, FISH demonstrated 22 consensus ALK+ and six ALK wild type
tumors. Preoptimization IHC scores from 12 centers with 5A4 and the percent
abnormal cells by FISH from 12 centers showed intraclass correlation coefficients
of 0.83 and 0.68, respectively. IHC optimization improved the intraclass
correlation coefficients to 0.94. Factors affecting FISH scoring and outliers
were identified. Post-optimization concurrent IHC/FISH testing in 373 informative
cases revealed 100% sensitivity and specificity for IHC versus FISH. CONCLUSIONS:
Multicenter standardization study may accelerate the implementation of ALK
testing protocols across a country/region. Our data support the use of an
appropriately validated IHC assay to screen for ALK+ lung cancers.
PMID- 25122423
TI - Inherited variation in the ATP-binding cassette transporter ABCB1 and survival
after chemotherapy for stage III-IV lung cancer.
AB - BACKGROUND: The ATP-binding cassette transporter gene ABCB1 and the glutathione S
transferase gene GSTP1 code for a multidrug resistance protein and for a
detoxifying phase II metabolic enzyme, respectively, with substrate specificities
that include chemotherapy drugs often used to treat lung cancer. METHODS: We
genotyped 11 ABCB1 and eight GSTP1 single nucleotide polymorphisms (SNPs) in 698
white lung cancer patients (all current or former cigarette smokers) and used log
rank test statistics and proportional hazards regression to evaluate associations
between SNP genotype and survival. RESULTS: Using data from all 698 cases, one
SNP in ABCB1 (rs2235013) was statistically significantly associated with overall
survival (p = 0.038, log-rank test). Chemotherapy and stage jointly (p = 0.025)
significantly modified the association between rs2235013 and survival, with
statistically significant (p = 0.013, log-rank test) association observed in the
subgroup of stage III to IV lung cancer patients who received chemotherapy as
part of their first course of treatment (n = 160; 93.1% nonsmall cell). Patients
who inherited the minor T allele at ABCB1 rs2235013 experienced better overall
survival and recurrence-free survival (hazard ratio, per minor T allele, [95%
confidence interval]: 0.66 [0.49-0.90] and 0.55 [0.31-0.95], respectively;
adjusted for year of diagnosis, sex, age at diagnosis, cigarette pack years, and
stage). In addition, in the advanced stage chemotherapy-treated subgroup, four
ABCB1 SNPs (rs6949448, rs2235046, rs1128503, and rs10276036) in mutual high
linkage disequilibrium with rs2235013 and an independent ABCB1 SNP (rs1045642)
showed statistically significant association (p < 0.05) with survival.
CONCLUSIONS: Inherited variation in ABCB1 may affect survival specifically in
advanced stage lung cancer patients who receive chemotherapy.
PMID- 25122424
TI - A prospective study of tumor suppressor gene methylation as a prognostic
biomarker in surgically resected stage I to IIIA non-small-cell lung cancers.
AB - INTRODUCTION: While retrospective analyses support an association between early
tumor recurrence and tumor suppressor gene promoter methylation in early-stage
non-small-cell lung cancers (NSCLCs), few studies have investigated this question
prospectively. METHODS: Primary tumor tissue from patients with resected
pathologic stage I to IIIA NSCLCs was collected at the time of surgery and
analyzed for promoter methylation via methylation-specific reverse transcriptase
polymerase chain reaction (MethyLight). The primary objective was to determine an
association between promoter methylation of 10 individual tumor suppressor genes
(CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, SOCS3, and ADAMTS8) and
recurrence-free survival (RFS), with the secondary objectives of determining
association with overall survival (OS), and relation to clinical or pathologic
features. RESULTS: A total of 107 patients had sufficient tumor tissue for
successful promoter methylation analysis. Majority of patients were
former/current smokers (88%) with lung adenocarcinoma (78%) and pathologic stage
I disease (62%). Median follow-up was 4 years. When controlled for pathologic
stage, promoter methylation of the individual genes CDKN2A, CDH13, RASSF1, APC,
MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8 was not associated with RFS. Promoter
methylation of the same genes was not associated with OS except for DAPK1 which
was associated with improved OS (p = 0.03). The total number of genes with
methylated promoters did not correlate with RFS (p = 0.89) or OS (p = 0.55).
CONCLUSION: Contrary to data established by previous retrospective series, tumor
suppressor gene promoter methylation (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1,
DAPK1, WIF1, and ADAMTS8) was not prognostic for early tumor recurrence in this
prospective study of resected NSCLCs.
PMID- 25122425
TI - The prognostic significance of focal adhesion kinase expression in stage I non
small-cell lung cancer.
AB - INTRODUCTION: Focal adhesion kinase (FAK) plays a significant role in cancer cell
survival signaling and is overexpressed in various malignancies, including lung
cancer. Previous studies suggest that FAK overexpression is an independent factor
predicting poor prognosis in non-small-cell lung cancer (NSCLC). The aim of this
study is to confirm these findings specifically in stage I NSCLC. METHODS: A
retrospective tissue microarray (TMA) analysis of FAK protein expression by
immunohistochemistry was performed in 157 surgically resected stage I NSCLC
specimen and in the corresponding matched normal lung tissue. The FAK 4.47
monoclonal antibody was used for FAK immunostaining. The scoring system of
triplicate tumor cores included intensity of staining plus extent of staining for
a composite score that ranged from 0 to 6. The association between FAK score and
survival was evaluated. RESULTS: There were 103 stage IA and 54 stage IB
patients, with mean follow-up of 5.5 years. Normal lung alveoli and interstitial
tissue had mean FAK score of 0 (median score 0, range 0 to 2). Tumor samples had
mean FAK score 3.1 (median score 3.5, range 0-6), with 57% of the samples having
FAK score >= 3. Continuous FAK score was not associated with demographic data,
tumor histology, or grade, nor survival in this cohort of stage I NSCLC patients.
CONCLUSIONS: FAK is expressed in more than 50% of stage I NSCLC lung cancer but
not in normal lung alveoli and interstitial tissue. FAK expression is not
associated with survival outcome in this North American cohort.
PMID- 25122426
TI - DNMT3B overexpression by deregulation of FOXO3a-mediated transcription repression
and MDM2 overexpression in lung cancer.
AB - INTRODUCTION: DNA methyltransferase 3B (DNMT3B) contributes to de novo DNA
methylation and its overexpression promotes tumorigenesis. However, whether
DNMT3B is upregulated by transcriptional deregulation remains unclear. METHODS:
We studied the transcriptional repression of DNMT3B by forkhead O transcription
factor 3a (FOXO3a) in lung cancer cell, animal, and clinical models. RESULTS: The
results of luciferase reporter assay showed that FOXO3a negatively regulated
DNMT3B promoter activity by preferentially interacting with the binding element
FOXO3a-E (+166 to +173) of DNMT3B promoter. Ectopically overexpressed FOXO3a or
combined treatment with doxorubicin to induce FOXO3a nuclear accumulation further
bound at the distal site, FOXO3a-P (-249 to -242) by chromatin
immunoprecipitation assay. Knockdown of FOXO3a resulted in an open chromatin
structure and high DNMT3B mRNA and protein expression. Abundant FOXO3a repressed
DNMT3B promoter by establishing a repressed chromatin structure. Note that FOXO3a
is a degradation substrate of MDM2 E3-ligase. Cotreatment with doxorubicin and
MDM2 inhibitor, Nutlin-3, further enforced abundant nuclear accumulation of
FOXO3a resulting in decrease expression of DNMT3B leading to synergistic
inhibition of tumor growth and decrease of methylation status on tumor suppressor
genes in xenograft specimens. Clinically, lung cancer patients with DNMT3B high,
FOXO3a low, and MDM2 high expression profile correlated with poor prognosis
examined by immunohistochemistry and Kaplan-Meier survival analysis. CONCLUSIONS:
We reveal a new mechanism that FOXO3a transcriptionally represses DNMT3B
expression and this regulation can be attenuated by MDM2 overexpression in human
lung cancer model. Cotreatment with doxorubicin and Nutlin-3 is a novel
therapeutic strategy through epigenetic modulation.
PMID- 25122427
TI - RET mutation and expression in small-cell lung cancer.
AB - BACKGROUND: There is growing interest in defining the somatic mutations
associated with small-cell lung cancer (SCLC). Unfortunately, a serious blockade
to genomic analyses of this disease is a limited access to tumors because surgery
is rarely performed. We used our clinical/pathologic database of SCLC patients to
determine the availability of biopsy specimens that could be used for genomic
studies and to identify tumors for initial oncogene analysis. METHODS: DNA was
extracted from six tumors, three primary and three metastatic, and analyzed by
SEQUENOM platform technology. RESULTS: Primary-resected tumor tissue represents
less than 3% of all diagnostic specimens in this disease, highlighting the
limited access to tissue sufficient for comprehensive genomic analyses. We
identified an activating M918T RET somatic mutation in a metastatic SCLC tumor
specimen. Bioinformatic search identified RET mutations in other SCLC studies.
Stable overexpression of both mutant M918T and wild-type RET in two SCLC cell
lines, H1048 and SW1271, activated ERK signaling, MYC expression, and increased
cell proliferation, particularly by mutant RET. Stable cells became sensitized to
the RET tyrosine kinase inhibitors, vandetanib and ponatinib. Further analysis of
RET mRNA expression in SCLC revealed wide variability in both cells and tumors,
and SCLC cells demonstrated significantly higher RET expression compared with
adenocarcinoma lung cells. CONCLUSIONS: Our data suggest that a subpopulation of
SCLC patients may derive benefit from tyrosine kinase inhibitors targeting RET.
Coupled with the presence of RET fusion proteins in non-small-cell lung cancer,
our data indicate an emerging role for RET in SCLC.
PMID- 25122428
TI - Therapeutic priority of the PI3K/AKT/mTOR pathway in small cell lung cancers as
revealed by a comprehensive genomic analysis.
AB - INTRODUCTION: The information regarding therapeutically relevant genomic
alterations in small cell lung cancer (SCLC) is not well developed. We analyzed
the SCLC genome using an integrative approach to stratify the targetable
alterations. METHODS: We performed whole exon sequencing (n = 51) and copy number
analysis (n =47) on surgically resected tumors and matched normal tissue samples
from treatment-naive Japanese SCLC patients. RESULTS: The demographics of the 51
patients included in this study were as follows: median age, 67 years (range, 42
86 years); female, 9 (18%); history of smoking, 50 (98%); and pathological stage
I/II/III/IV, 28/13/9/1, respectively. The average number of nonsynonymous
mutations was 209 (range, 41-639; standard deviation, 130). We repeatedly
confirmed the high prevalence of inactivating mutations in TP53 and RB1, and the
amplification of MYC family members. In addition, genetic alterations in the
PI3K/AKT/mTOR pathway were detected in 36% of the tumors: PIK3CA, 6%; PTEN, 4%;
AKT2, 9%; AKT3, 4%; RICTOR, 9%; and mTOR, 4%. Furthermore, the individual changes
in this pathway were mutually exclusive. Importantly, the SCLC cells harboring
active PIK3CA mutations were potentially targetable with currently available PI3K
inhibitors. CONCLUSIONS: The PI3K/AKT/mTOR pathway is distinguishable in SCLC
genomic alterations. Therefore, a sequencing-based comprehensive analysis could
stratify SCLC patients by potential therapeutic targets.
PMID- 25122429
TI - Safety and effectiveness of bevacizumab-containing treatment for non-small-cell
lung cancer: final results of the ARIES observational cohort study.
AB - INTRODUCTION: Bevacizumab, a recombinant humanized monoclonal antibody against
vascular endothelial growth factor, was approved by the US Food and Drug
Administration for the treatment of advanced non-small-cell lung cancer (NSCLC)
in combination with carboplatin and paclitaxel. ARIES (Avastin Regimens:
Investigation of Effectiveness and Safety), a prospective observational cohort
study, evaluated outcomes in a large, community-based population of patients with
first-line NSCLC. METHODS: From 2006 to 2009, ARIES enrolled patients with
locally advanced or metastatic NSCLC who were eligible for bevacizumab, excluding
those with predominantly squamous histology. Patients were required to provide
informed consent and to have initiated bevacizumab with chemotherapy within 4
months before enrollment. There were no protocol-defined treatments or
assessments. The dosing of bevacizumab and chemotherapy, and the choice of
chemotherapy regimen, was at the discretion of the treating physician. RESULTS:
ARIES enrolled 1967 patients with first-line NSCLC. At study closure, median
follow-up was 12.5 months (range, 0.2-65.5). Median age was 65 years (range, 31
93), and 252 patients (12.8%) identified as never smokers. Median progression
free survival was 6.6 months (95% confidence interval, 6.3-6.9), and median
overall survival was 13.0 months (95% confidence interval, 12.2-13.8) with first
line bevacizumab plus chemotherapy. Incidences of bevacizumab-associated adverse
events (19.7% overall) were consistent with those in randomized controlled trials
of bevacizumab in NSCLC. CONCLUSION: Results from ARIES demonstrate similar
outcomes to randomized controlled trials of bevacizumab when added to standard
chemotherapy in a real-world patient population with advanced NSCLC.
PMID- 25122430
TI - Gefitinib treatment in EGFR mutated caucasian NSCLC: circulating-free tumor DNA
as a surrogate for determination of EGFR status.
AB - INTRODUCTION: In the phase IV, open-label, single-arm study NCT01203917, first
line gefitinib 250 mg/d was effective and well tolerated in Caucasian patients
with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell
lung cancer (previously published). Here, we report EGFR mutation analyses of
plasma-derived, circulating-free tumor DNA. METHODS: Mandatory tumor and
duplicate plasma (1 and 2) baseline samples were collected (all screened
patients; n = 1060). Preplanned, exploratory analyses included EGFR mutation (and
subtype) status of tumor versus plasma and between plasma samples. Post hoc,
exploratory analyses included efficacy by tumor and plasma EGFR mutation (and
subtype) status. RESULTS: Available baseline tumor samples were 1033 of 1060 (118
positive of 859 mutation status known; mutation frequency, 13.7%). Available
plasma 1 samples were 803 of 1060 (82 positive of 784 mutation status known;
mutation frequency, 10.5%). Mutation status concordance between 652 matched tumor
and plasma 1 samples was 94.3% (95% confidence interval [CI], 92.3-96.0)
(comparable for mutation subtypes); test sensitivity was 65.7% (95% CI, 55.8
74.7); and test specificity was 99.8% (95% CI, 99.0-100.0). Twelve patients of
unknown tumor mutation status were subsequently identified as plasma mutation
positive. Available plasma 2 samples were 803 of 1060 (65 positive of 224
mutation status-evaluable and -known). Mutation status concordance between 224
matched duplicate plasma 1 and 2 samples was 96.9% (95% CI, 93.7-98.7). Objective
response rates are as follows: mutation-positive tumor, 70% (95% CI, 60.5-77.7);
mutation-positive tumor and plasma 1, 76.9% (95% CI, 65.4-85.5); and mutation
positive tumor and mutation-negative plasma 1, 59.5% (95% CI, 43.5-73.7). Median
progression-free survival (months) was 9.7 (95% CI, 8.5-11.0; 61 events) for
mutation-positive tumor and 10.2 (95% CI, 8.5-12.5; 36 events) for mutation
positive tumor and plasma 1. CONCLUSION: The high concordance, specificity, and
sensitivity demonstrate that EGFR mutation status can be accurately assessed
using circulating-free tumor DNA. Although encouraging and suggesting that plasma
is a suitable substitute for mutation analysis, tumor tissue should remain the
preferred sample type when available.
PMID- 25122431
TI - Reproducibility of histopathological diagnosis in poorly differentiated NSCLC: an
international multiobserver study.
AB - INTRODUCTION: The 2004 World Health Organization classification of lung cancer
contained three major forms of non-small-cell lung cancer: squamous cell
carcinoma (SqCC), adenocarcinoma (AdC), and large cell carcinoma. The goal of
this study was first, to assess the reproducibility of a set of histopathological
features for SqCC in relation to other poorly differentiated non-small-cell lung
cancers and second, to assess the value of immunohistochemistry in improving the
diagnosis. METHODS: Resection specimens (n = 37) with SqCC, large cell carcinoma,
basaloid carcinoma, sarcomatoid carcinoma, lymphoepithelial-like carcinoma, and
solid AdC, were contributed by the participating pathologists. Hematoxylin and
eosin (H&E) stained slides were digitized. The diagnoses were evaluated in two
ways. First, the histological criteria were evaluated and the (differential)
diagnosis on H&E alone was scored. Second, the added value of additional stains
to make an integrated diagnosis was examined. RESULTS: The histologic criteria
defining SqCC were consistently used, but in poorly differentiated cases they
were infrequently present, rendering the diagnosis more difficult. Kappa scores
on H&E alone were for SqCC 0.46, large cell carcinoma 0.25, basaloid carcinoma
0.27, sarcomatoid carcinoma 0.52, lymphoepithelial-like carcinoma 0.56, and solid
AdC 0.21. The kappa score improved with the use of additional stains for SqCC
(combined with basaloid carcinoma) to 0.57, for solid AdC to 0.63. CONCLUSION:
The histologic criteria that may be used in the differential diagnosis of poorly
differentiated lung cancer were more precisely refined. Furthermore, additional
stains improved the reproducibility of histological diagnosis of SqCC and AdC,
uncovering information that was not present in routine H&E stained slides.
PMID- 25122432
TI - The prognostic impact of KRAS, its codon and amino acid specific mutations, on
survival in resected stage I lung adenocarcinoma.
AB - BACKGROUND: Despite complete surgical resection, patients with stage I non-small
cell lung cancer (NSCLC) are at risk for disease recurrence. The impact of common
oncogenic driver mutations on prognosis in stage I NSCLC is limited. The pure
prognostic value of KRAS mutational status was explored in resected stage I lung
adenocarcinoma. METHODS: Mutation status was tested in patients who had complete
resection of stage I lung adenocarcinoma without any adjuvant therapy, using a
multiplex polymerase chain reaction)-based assay. Disease-free survival (DFS) and
overall survival (OS) were compared between patients with KRAS-mutant (KRAS-MUT),
KRAS-MUT subtypes, and KRAS wild-type (KRAS-WT) tumors. RESULTS: A total of 312
patients were included in this analysis; 127 harbored KRAS mutations and 185 had
KRAS-WT tumors. When compared with KRAS-WT, KRAS-MUT was associated with
significantly shorter OS (hazard ratio 4.36, 95% confidence interval 2.09-9.07; p
< 0.0001) and DFS (hazard ratio 3.62, 95% confidence interval 2.11-6.22; p <
0.0001). When stratifying KRAS-WT patients based on EGFR status, KRAS-MUT
patients had worse OS (p = 0.0001) and DFS (p < 0.0001) than patients with EGFR
MUT and EGFR-WT/KRAS-WT (WT/WT). Patients with codon 12 mutations had superior
DFS (p = 0.0314), but there were no differences in OS compared with mutations
found in codons 13 and 61 (p = 0.1772). We observed better DFS associated with
G12C/G12V mutations compared with other amino acid specific KRAS mutations (p =
0.0271) with a trend towards improved OS (p = 0.0636). Multivariate analysis
identified KRAS mutation as independent predictor of worse OS (p = 0.001) and DFS
(p < 0.0001). CONCLUSION: KRAS is an independent prognostic marker in resected
stage I lung adenocarcinoma. Differential outcomes are associated with codon and
amino acid specific KRAS mutations.
PMID- 25122433
TI - Toxicities of organs at risk in the mediastinal and hilar regions following
stereotactic body radiotherapy for centrally located lung tumors.
AB - INTRODUCTION: We investigated tolerable doses to organs at risk (OARs) in the
mediastinum and pulmonary hilum following stereotactic body radiotherapy for
centrally located lung tumors. METHODS: Between 2005 and 2012, 381 patients with
lung tumors were treated with stereotactic body radiotherapy of 40 to 60 Gy in
five fractions. From among these patients, we extracted those who received
greater than 25 Gy irradiation to OARs and analyzed dosimetric factors in
relation to grade 3 to 5 toxicities. RESULTS: In total, 398 OARs in 133 patients
were analyzed, with a median follow-up of 33 (range, 3-87) months. The numbers
receiving greater than 25 Gy irradiation to the aorta, vena cava, pulmonary
artery, pulmonary vein, bronchus, trachea, heart, and esophagus were 72, 33, 73,
60, 55, 13, 69, and 23, respectively. The corresponding median Dmax 0.5 ml were
43.8, 32.0, 32.2, 29.1, 28.4, 28.7, 41.1, and 21.7 Gy. Of these patients, two
developed grade 5 and one grade 3 hemoptysis, and two had grade 3 obstructive
pneumonia. Two patients with grade 5 hemoptysis received high doses at the
pulmonary artery and bronchus (59.2 and 54.4 Gy, and 61.3 and 59.6 Gy,
respectively). No other grade 3 to 5 toxicities occurred. CONCLUSION: Therapeutic
indications and dose-intensity should be carefully determined for patients with
central tumors, especially when doses to the pulmonary artery and bronchus in the
pulmonary hilum exceed 50 Gy. Tolerable doses for other OARs might, however, be
higher than in this study, though longer follow-up is necessary to assess this
possibility.
PMID- 25122434
TI - Can computed tomography characteristics predict outcomes in patients undergoing
radial endobronchial ultrasound-guided biopsy of peripheral lung lesions?
AB - INTRODUCTION: Percutaneous computed tomography (CT)-guided lung biopsy is a
standard minimally invasive technique for sampling peripheral lung lesions.
Radial endobronchial ultrasound (EBUS) offers an alternative approach but it has
yet to be defined which patients are most suited to this procedure. The primary
aim of this study was to investigate whether CT characteristics could predict the
success of radial EBUS-guided sampling. METHODS: The University Hospital South
Manchester provides a radial EBUS service, under conscious sedation without
fluoroscopy, double-hinged curettes, or guide sheaths, to a large cancer Network
in the United Kingdom. This retrospective analysis of a prospectively maintained
database included all patients undergoing radial EBUS from January 2011 to June
2013. Lesion size, structure, location, and presence of a bronchus sign on
thoracic CT were analyzed against predefined outcomes using multivariate
analysis. RESULTS: One-hundred and seventeen patients underwent radial EBUS in
the study period (mean age 69.5, mean lesion size 36.6 mm). The presence of a
bronchus sign on CT was the only independent predictor of all predefined
outcomes: (1) lesion identification with radial EBUS, (2) positioning of probe
within the center of the lesion, and (3) accurate pathological diagnosis; odds
ratio (OR) 31.1 (7.8-123.9, p < 0.0001), OR 44.8 (5.6-354.9, p < 0.0001) and OR
46.6 (11.1-195.3, p < 0.0001) respectively. The sensitivity and diagnostic
accuracy for those patients with a bronchus sign on CT was 87.3% and 86.7%
compared with 12.5% and 11.1% for those lacking the bronchus sign. DISCUSSION:
The patients most likely to benefit from radial EBUS, without the use of
adjuncts, are those with a bronchus sign on CT.
PMID- 25122435
TI - Re-evaluating the optimal radiation dose for definitive chemoradiotherapy for
esophageal squamous cell carcinoma.
AB - BACKGROUND: The optimal radiation dose for treating esophageal squamous cell
carcinoma (ESCC) has long been debated. We evaluated if doses greater than 50.4
Gy delivered with modern techniques are beneficial in terms of tumor control,
survival, and toxicity. METHODS: We included 193 consecutive patients with ESCC
treated with definitive concurrent chemoradiotherapy from 1998 to 2012. Patients
were treated to a dose of <=50.4 Gy (low-dose, n = 137) or greater than 50.4 Gy
(high-dose, n = 56). Tumor response, local-regional control, survival, and
treatment toxicity were compared between groups. RESULTS: High-dose group had a
significantly lower local failure rate (17.9% versus 34.3%, p = 0.024) and a
marginal better 5-year local-regional failure-free survival (68.7% versus 55.9%,
p = 0.052) than the low-dose group. No significant differences were found between
high- and low-dose groups in tumor complete response rate (p = 0.975), regional
failure rate (p = 0.336), distant metastasis rate (p = 0.390), or 5-year overall
survival (p = 0.617). No difference in the incidence of toxic effects was
observed between the two groups except for grade 3 skin reaction (12.5% [high]
versus 2.2% [low], p < 0.001) and grade greater than or equal to 3 esophageal
stricture (32.1% [high] versus 18.2% [low], p = 0.037). CONCLUSIONS: Local tumor
control might be improved by higher dose of greater than 50.4 Gy, when delivered
with modern techniques and concurrent chemotherapy, at the consequence of
increased toxicity without impact on overall survival.
PMID- 25122436
TI - Clinical characteristics, tumor, node, metastasis status, and mutation rate in
domain of epidermal growth factor receptor gene in serbian patients with lung
adenocarcinoma.
AB - OBJECTIVE: Mutation rate in domain of EGFR gene varies between populations of
lung cancer patients. Primary aim of this study was to analyze clinical and
pathological characteristics, and tumor, node, metastasis status and stage of
diseases, in relation to mutation status. METHODS: After histological
confirmation of lung adenocarcinoma tissue obtained during bronchoscopy was
consecutively sent for EGFR testing. Genomic DNA extraction was performed with
the QIAamp DNA FFPE Tissue kit. Clinical data for multivariate analysis were
extracted from hospital based-lung cancer registry. RESULTS: Among 360 tested
patients, there was 67.8% males and 32.2% females, aged 61 +/- 9.8 years.
Majority of patients were smokers (57.0%) with Eastern Cooperative Oncology Group
1 performance status (92.2%). Mutation in EGFR gene was detected in 42 (11.7%)
patients. Deletion in exon 19 was detected in 24 (6.7%) patients, mutation in
exon 21 in 17 (4.7%), and mutation in exon 18 in one patient (0.3%). Patients
were mostly diagnosed in stage IV adenocarcinoma (74.4%). Statistically
significant differences were determined in relation to smoking (p < 0.001), T
descriptor (size; p = 0.019) and gender (p = 0.002). CONCLUSIONS: Mutation rate
in domain of EGFR gene in investigated lung cancer population is in range with
reported data in Caucasian race. Smoking, T descriptor and gender were found to
be related to the EGFR status.
PMID- 25122438
TI - Popcorn in the lung.
PMID- 25122437
TI - Biomarker analyses from a randomized, placebo-controlled, phase IIIb trial
comparing bevacizumab with or without erlotinib as maintenance therapy for the
treatment of advanced non-small-cell lung cancer (ATLAS).
AB - INTRODUCTION: ATLAS compared bevacizumab plus erlotinib (B+E) with bevacizumab
plus placebo (B+P) as maintenance therapy after first-line bevacizumab plus
chemotherapy (B+C) for advanced non-small-cell lung cancer (NSCLC). Prespecified
biomarkers were prospectively evaluated. METHODS: Tumor samples were analyzed
for: epidermal growth factor receptor (EGFR) expression (immunohistochemistry
[IHC]); EGFR gene copy number (fluorescence in-situ hybridization [FISH]); EGFR
mutations (exon 19 deletions/L858R mutations); and KRAS mutations (exons 2/3).
Progression-free survival (PFS) and overall survival (OS) were estimated.
RESULTS: Of 743 patients randomized to receive maintenance treatment (after four
cycles of B+C without progression), 190 (B+E) and 177 (B+P) were evaluable for
biomarker status. Median PFS (from randomization) was 4.4 months (B+E) versus 3.7
months (B+P; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.57-0.99),
which was numerically similar to the intent-to-treat PFS. PFS benefit of B+E was
observed across most biomarker subgroups. EGFR IHC, EGFR FISH, and EGFR/KRAS
mutation status were not predictive of outcome. B+E-treated patients with EGFR
mutation-positive NSCLC had longer PFS compared with B+P-treated patients (HR,
0.44; 95% CI, 0.22-0.86; p = 0.0139). Patients with KRAS wild-type disease had
significant PFS improvements with B+E, compared with B+P (HR, 0.66; 95% CI, 0.485
0.914; p = 0.0105). No OS benefit of B+E was observed. CONCLUSIONS: Patients with
KRAS wild-type or EGFR mutation-positive NSCLC derived PFS benefits from B+E.
However, EGFR IHC, EGFR FISH, and EGFR or KRAS mutation status were not strongly
predictive of survival. A larger sample size would be needed to confirm the
initial trends observed in this study.
PMID- 25122439
TI - Effective treatment with icotinib in primary adenoid cystic carcinoma of the lung
with liver metastasis.
PMID- 25122440
TI - Cisplatin or Carboplatin for advanced non-small-cell lung cancer?
PMID- 25122441
TI - EGFR mutations in Asian patients with advanced lung adenocarcinoma.
PMID- 25122442
TI - EGFR mutation detection by polymerase chain reaction-direct sequencing and allele
specific real-time PCR.
PMID- 25122443
TI - Prevalence of selected chronic digestive conditions, United States - july
december 1968.
AB - This report on chronic digestive conditions is the first of a new series of
reports on the prevalence of selected chronic conditions" based on data collected
as a part of the Health Interview Survey. Estimates of the prevalence of chronic
diseases or impairments have been made from information reported in the Health
Interview Survey since its inception in July of 1957. Since that time efforts
have been made to improve the quality of the data on the prevalence of chronic
conditions. Chronic conditions reported in interviews may be described as those
of which the respondent is aware and which he is willing to report to an
interviewer. The diagnostic accuracy of reported conditions is dependent on the
information the attending physician has passed on to the family or, in the
absence of medical attention, on the previous medical experience or education of
the family. Prior to 1968 in the Health Interview Survey an attempt was made to
obtain data on all chronic conditions that respondents had had during the. 12
month period before the date of the interview; checklists of about 40 to 50
chronic conditions and impairments were used. Beginning in 1968 the procedure was
changed, and data were obtained only for chronic conditions within one system of
conditions each year (although data on all conditions causing long term
limitations of activity, disability days, and physician visits were still
obtained). In 1968 respondents were read a list of 25 conditions, the majority of
which were digestive conditions (see question 16a, appendix III). A more detailed
discussion of basic changes made in 1968 can be found in Vital and Health
Statistics, Series 2, Number 48.
PMID- 25122444
TI - A bispecific fusion protein and a bifunctional enediyne-energized fusion protein
consisting of TRAIL, EGFR peptide ligand, and apoprotein of lidamycin against
EGFR and DR4/5 show potent antitumor activity.
AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mainly induces
apoptosis through the extrinsic death receptor-induced pathway by ligation with
death receptor 4 (DR4) and death receptor 5 (DR5). On the basis of the antitumor
activity to cancer cells and no cytotoxity to normal cells of TRAIL and the
target of the epidermal growth factor receptor (EGFR) ligand peptide, the study
constructed a new bispecific fusion protein and a new bifunctional enediyne
energized fusion protein and investigated their antitumor efficacy. Bispecific
fusion protein Ec-LDP-TRAIL showed potent binding activity to cancer cell lines
with a high expression of EGFR or DR4/DR5 such as A431 and H460 cells, whereas
poor binding activity to NIH/3T3 cells with low expressing EGFR and DR4/DR5. Ec
LDP-TRAIL also showed more potent cytotoxicity to A431 and H460 cells than Ec
LDP, which could result from the TRAIL-inducing apoptosis. Results of an in-vivo
efficacy study showed that Ec-LDP-TRAIL at a dose of 10 mg/kg decreased the
growth of epidermoid carcinoma A431 xenografts by 80.19% (P < 0.01) on day 26.
Immunohistochemical detection of nuclear antigen factor Ki-67 suggested that Ec
LDP-TRAIL effectively induced cell necrosis and inhibited cell proliferation of
tumor. From IC50 values, bispecific and bifunctional energized fusion protein Ec
LDP-TRAIL-AE was more potent and selective in its cytotoxicity against different
carcinoma cell lines than corresponding lidamycin in vitro and induction of the
cleavage of poly(ADP-ribose)polymerase was observed in A431 cells treated with Ec
LDP-TRAIL-AE and lidamycin, respectively. Ec-LDP-TRAIL-AE also significantly
inhibited the growth of A431 xenografts in a nude mouse model. These properties
suggested that Ec-LDP-TRAIL and Ec-LDP-TRAIL-AE may be promising candidates for
targeted cancer therapy.
PMID- 25122445
TI - Surgical site infections after deep brain stimulation surgery: frequency,
characteristics and management in a 10-year period.
AB - BACKGROUND/AIMS: Deep brain stimulation (DBS) implant infection is a feared
complication, as it is difficult to manage and leads to increased patient
morbidity. We wanted to assess the frequency and possible risk factors of DBS
related infections at our centre. In the purpose of evaluating treatment options,
we also analyzed treatment, and the clinical and microbiological characteristics
of the infections. METHODS: Electronic medical records of all patients undergoing
DBS surgery at our centre, from 2001 through 2010, were retrospectively reviewed.
RESULTS: Of the 588 procedures performed 33 (5.6%) led to an infection. Some
patients underwent several procedures, thus 32 out of totally 368 patients
(8.7%), and 19 out of 285 patients (6.7%) who received primary lead implantation,
developed an infection. Most infections (52%) developed within the first month
and 79% within three months. In the majority of the infections (79%) hardware
removal was performed. Staphylococcus aureus infections were the most frequent
(36%), and more likely to have earlier onset, pus formation, a more aggressive
development and lead to hardware removal. No risk factors were identified.
CONCLUSIONS: Our results indicate that infections with more severe symptoms and
growth of staphylococcus aureus should be treated with local hardware removal and
antibiotic therapy. In other infections, an initial trial of antibiotic treatment
could be considered. New knowledge about the microbiology of DBS related
infections may lead to more effective antimicrobial treatment.
PMID- 25122447
TI - Experimental parameterisation of principal physics in buoyancy variations of
marine teleost eggs.
AB - It is generally accepted that the high buoyancy of pelagic marine eggs is due to
substantial influx of water across the cell membrane just before ovulation. Here
we further develop the theoretical basis by applying laboratory observations of
the various components of the fertilized egg in first-principle equations for egg
specific gravity (rho(egg)) followed by statistical validation. We selected
Atlantic cod as a model animal due to the affluent amount of literature on this
species, but also undertook additional dedicated experimental works. We found
that specific gravity of yolk plus embryo is central in influencing rho(egg) and
thereby the buoyancy. However, our established framework documents the effect on
rho(egg) of the initial deposition of the heavy chorion material in the gonad
prior to spawning. Thereafter, we describe the temporal changes in rho(egg)
during incubation: Generally, the eggs showed a slight rise in rho(egg) from
fertilization to mid-gastrulation followed by a gradual decrease until full
development of main embryonic organs just before hatching. Ontogenetic changes in
rho(egg) were significantly associated with volume and mass changes of yolk plus
embryo. The initial rho(egg) at fertilization appeared significantly influenced
by the chorion volume fraction which is determined by the combination of the
final chorion volume of the oocyte and of the degree of swelling (hydrolyzation)
prior to spawning. The outlined principles and algorithms are universal in nature
and should therefore be applicable to fish eggs in general.
PMID- 25122448
TI - The impact of past direct-personal traumatic events on 12-month outcome in first
episode psychotic mania: trauma and early psychotic mania.
AB - OBJECTIVE: Past traumatic events have been associated with poorer clinical
outcomes in people with bipolar disorder. However, the impact of these events in
the early stages of the illness remains unclear. The aim of this study was to
investigate whether prior traumatic events were related to poorer outcomes 12
months following a first episode of psychotic mania. METHODS: Traumatic events
were retrospectively evaluated from patient files in a sample of 65 participants
who had experienced first episode psychotic mania. Participants were aged between
15 and 28 years and were treated at a specialised early psychosis service.
Clinical outcomes were measured by a variety of symptomatic and functioning
scales at the 12-month time-point. RESULTS: Direct-personal traumatic experiences
prior to the onset of psychotic mania were reported by 48% of the sample.
Participants with past direct-personal trauma had significantly higher symptoms
of mania (p=0.02), depression (p=0.03) and psychopathology (p=0.01) 12 months
following their first episode compared to participants without past direct
personal trauma, with medium to large effects observed. After adjusting for
baseline scores, differences in global functioning (as measured by the Global
Assessment of Functioning scale) were non-significant (p=0.05); however,
participants with past direct-personal trauma had significantly poorer social and
occupational functioning (p=0.04) at the 12-month assessment with medium effect.
CONCLUSIONS: Past direct-personal trauma may predict poorer symptomatic and
functional outcomes after first episode psychotic mania. Limitations include that
the findings represent individuals treated at a specialist early intervention
centre for youth and the retrospective assessment of traumatic events may have
been underestimated.
PMID- 25122450
TI - Theory of Mind and attachment styles in people with psychotic disorders, their
siblings, and controls.
AB - OBJECTIVE: Impaired Theory of Mind (ToM) and insecure (adult) attachment styles
have been found in persons with schizophrenia as well as in their healthy
siblings. ToM refers to the ability to infer mental states of self and others
including beliefs and emotions. Insecure attachment is proposed to underlie
impaired ToM, and comprises avoidant (discomfort with close relationships, high
value of autonomy) and anxious (separation anxiety, dependency on others)
attachment. Insight into the association between attachment style and ToM is
clinically relevant, as it enhances our understanding and clinical approach to
social dysfunction in schizophrenia. Therefore, we studied the association
between insecure attachment styles and ToM in patients with schizophrenia, their
siblings, and healthy controls. METHODS: A total of 111 patients with a diagnosis
in the schizophrenia spectrum, 106 non-affected siblings and 63 controls
completed the Psychosis Attachment Measure, the Conflicting Beliefs and Emotions,
a subsection of the Wechsler Adult Intelligence Scale, and the Childhood Trauma
Questionnaire-Short Form. Severity of symptoms was assessed with the Community
Assessment of Psychic Experiences and the Positive and Negative Syndrome Scale.
RESULTS: After controlling for sex, intelligence, history of trauma and symptom
severity, avoidant attachment was significantly associated with cognitive as well
as with affective ToM, showing U-shaped associations, indicating better ToM
performance for patients with lower or higher levels of avoidant attachment
compared to medium levels. Anxious attachment in patients was associated with
more problems in cognitive ToM. CONCLUSION: The results from this study support
the idea that an anxious attachment style is associated with worse ToM
performance in patients. Results also suggested a potential protective role of
higher levels of avoidant attachment on ToM. These findings bear clinical
relevance, as activation of (insecure) attachment mechanisms may affect
interpersonal relations, as well as therapeutic working alliance. Further
clarification is needed, especially on associations between ToM and avoidant
attachment.
PMID- 25122449
TI - DSM-IV and DSM-5 social anxiety disorder in the Australian community.
AB - OBJECTIVE: Current and accurate estimates of prevalence, correlates, comorbid
concerns and treatment-seeking behaviours associated with disorders are essential
for informing policy, clinical practice and research. The most recent snapshot of
social anxiety disorder in Australia was published more than a decade ago, with
significant changes to the accessibility of mental health treatment services and
diagnostic measures occurring during this period. This paper aims to (i) update
the understanding of social anxiety disorder, its associations and patterns of
treatment-seeking behaviours in the Australian population, and (ii) explore the
impact of revised diagnostic criteria detailed in the Fifth Edition of the
Diagnostic and Statistical Manual of Mental Disorders (DSM-5) on prevalence
estimates. METHODS: The National Survey of Mental Health and Wellbeing (NSMHWB)
was conducted by the Australian Bureau of Statistics in 2007, collecting
information from a nationally representative random sample of 8841 Australians
aged 16-85 years. The presence of social anxiety disorder diagnostic criteria and
related disorders were assessed over 12 months and lifetime periods using the
World Mental Health Composite International Diagnostic Interview. RESULTS:
Profiles of social anxiety disorder were consistent with previous estimates, with
higher prevalence in females and younger age groups. Of the 8.4% of Australians
meeting criteria for social anxiety disorder at some point in their lifetime (12
month prevalence 4.2%), a majority also experienced comorbid mental health
concerns (70%). The revised performance-only specifier included in the DSM-5 was
applicable to only 0.3% of lifetime cases. Just over 20% of people reporting
social anxiety disorder as their primary concern sought treatment, most commonly
through general practitioners. CONCLUSIONS: Social anxiety disorder continues to
be prevalent in the Australian population and highly related to other disorders,
yet few people experiencing social anxiety disorder seek treatment.
PMID- 25122451
TI - Twelve-month prevalence and predictors of self-reported suicidal ideation and
suicide attempt among Korean adolescents in a web-based nationwide survey.
AB - OBJECTIVE: The suicide rate in South Korea was the highest among the Organisation
for Economic Co-operation and Development (OECD) countries in 2011. Although the
suicide rate in adolescents is lower than that of adults and is reported to be
decreasing in young males in some countries, it has consistently increased in
recent years in South Korea. We aimed to determine the prevalence, pattern, and
predictors of suicidal ideation and attempt in the past 12 months. METHODS: A
total sample of 72,623 adolescents aged 12-18 years who responded to a web-based
anonymous self-reported survey between September and October 2010 was used for
the analysis. RESULTS: The suicidal ideation and suicide attempt rates were 19.1%
and 4.9%, respectively. Being female, having a poor perceived socioeconomic
status and a poor perceived academic performance, subjective feelings of
depression, cigarette smoking, alcohol use, perceived general medical health, and
experiences of any involvement with sexual intercourse were the contributing
factors that predicted elevated risks for suicidal ideation and suicide attempt.
In contrast to previous reports in other countries, the suicide attempt rate in
Korean female adolescents peaked at age 13 years, and there were no differences
in suicidal ideation in females by age. There were no differences in both
suicidal ideation and attempt rates in males by age. CONCLUSION: A
multidisciplinary approach that takes into consideration the characteristics of
Korean adolescents with suicidal ideation or suicide attempt is warranted for
developing prevention and treatment programs.
PMID- 25122452
TI - Unsupervised eye pupil localization through differential geometry and local self
similarity matching.
AB - The automatic detection and tracking of human eyes and, in particular, the
precise localization of their centers (pupils), is a widely debated topic in the
international scientific community. In fact, the extracted information can be
effectively used in a large number of applications ranging from advanced
interfaces to biometrics and including also the estimation of the gaze direction,
the control of human attention and the early screening of neurological
pathologies. Independently of the application domain, the detection and tracking
of the eye centers are, currently, performed mainly using invasive devices.
Cheaper and more versatile systems have been only recently introduced: they make
use of image processing techniques working on periocular patches which can be
specifically acquired or preliminarily cropped from facial images. In the latter
cases the involved algorithms must work even in cases of non-ideal acquiring
conditions (e.g in presence of noise, low spatial resolution, non-uniform
lighting conditions, etc.) and without user's awareness (thus with possible
variations of the eye in scale, rotation and/or translation). Getting satisfying
results in pupils' localization in such a challenging operating conditions is
still an open scientific topic in Computer Vision. Actually, the most performing
solutions in the literature are, unfortunately, based on supervised machine
learning algorithms which require initial sessions to set the working parameters
and to train the embedded learning models of the eye: this way, experienced
operators have to work on the system each time it is moved from an operational
context to another. It follows that the use of unsupervised approaches is more
and more desirable but, unfortunately, their performances are not still
satisfactory and more investigations are required. To this end, this paper
proposes a new unsupervised approach to automatically detect the center of the
eye: its algorithmic core is a representation of the eye's shape that is obtained
through a differential analysis of image intensities and the subsequent
combination with the local variability of the appearance represented by self
similarity coefficients. The experimental evidence of the effectiveness of the
method was demonstrated on challenging databases containing facial images.
Moreover, its capabilities to accurately detect the centers of the eyes were also
favourably compared with those of the leading state-of-the-art methods.
PMID- 25122453
TI - Sorghum phytochrome B inhibits flowering in long days by activating expression of
SbPRR37 and SbGHD7, repressors of SbEHD1, SbCN8 and SbCN12.
AB - Light signaling by phytochrome B in long days inhibits flowering in sorghum by
increasing expression of the long day floral repressors PSEUDORESPONSE REGULATOR
PROTEIN (SbPRR37, Ma1) and GRAIN NUMBER, PLANT HEIGHT AND HEADING DATE 7 (SbGHD7,
Ma6). SbPRR37 and SbGHD7 RNA abundance peaks in the morning and in the evening of
long days through coordinate regulation by light and output from the circadian
clock. 58 M, a phytochrome B deficient (phyB-1, ma3R) genotype, flowered ~60 days
earlier than 100 M (PHYB, Ma3) in long days and ~11 days earlier in short days.
Populations derived from 58 M (Ma1, ma3R, Ma5, ma6) and R.07007 (Ma1, Ma3, ma5,
Ma6) varied in flowering time due to QTL aligned to PHYB/phyB-1 (Ma3), Ma5, and
GHD7/ghd7-1 (Ma6). PHYC was proposed as a candidate gene for Ma5 based on
alignment and allelic variation. PHYB and Ma5 (PHYC) were epistatic to Ma1 and
Ma6 and progeny recessive for either gene flowered early in long days. Light
signaling mediated by PhyB was required for high expression of the floral
repressors SbPRR37 and SbGHD7 during the evening of long days. In 100 M (PHYB)
the floral activators SbEHD1, SbCN8 and SbCN12 were repressed in long days and de
repressed in short days. In 58 M (phyB-1) these genes were highly expressed in
long and short days. Furthermore, SbCN15, the ortholog of rice Hd3a (FT), is
expressed at low levels in 100 M but at high levels in 58 M (phyB-1) regardless
of day length, indicating that PhyB regulation of SbCN15 expression may modify
flowering time in a photoperiod-insensitive manner.
PMID- 25122454
TI - Diverse expression of selected SMN complex proteins in humans with sporadic
amyotrophic lateral sclerosis and in a transgenic rat model of familial form of
the disease.
AB - BACKGROUND AND OBJECTIVE: There is circumstantial evidence linking sporadic
amyotrophic lateral sclerosis (ALS) cases to a malfunction or deficit of a
multimeric SMN complex that scrutinizes cellular RNAs; the core of this complex
is survival motor neuron (SMN, or gemin 1) protein. We intended to verify this
hypothesis by comparing the expression of both SMN and several other functionally
associated gemins in the anterior horn motoneurons of patients who died of
sporadic ALS (sALS), of transgenic rats with overexpression of the mutated human
superoxide dismutase 1 gene (SOD1(G93A)) that represent a model of familial ALS
(fALS), and of the respective controls. METHODS: Using archival material of
paraffin blocks with samples of human and rat spinal cords, immunohistochemical
reactions with antibodies against SMN and gemins 2, 3, and 4 were performed and
assessed by light microscopy. RESULTS: The expression of SMN and all other
studied gemins was observed in motoneurons of sALS patients, fALS rats, and in
all controls, although the intensity varied. The immunolabeling was most intense
in sALS patients with relatively fast disease course, and decreased with
increasing disease duration in both the human sALS and rat fALS material.
Irrespective of the disease stage, sALS material showed no or very low gemin 2
immunoreactivity, while clear gemin 2 immunoreactivity was observed in all fALS
rats and control material. CONCLUSION: The deficient expression of gemin 2 in
spinal cord motoneurons in human sALS may lead to a dysfunction and loss of
neuroprotective action of the SMN complex.
PMID- 25122455
TI - Dynamic mechanisms of neocortical focal seizure onset.
AB - Recent experimental and clinical studies have provided diverse insight into the
mechanisms of human focal seizure initiation and propagation. Often these
findings exist at different scales of observation, and are not reconciled into a
common understanding. Here we develop a new, multiscale mathematical model of
cortical electric activity with realistic mesoscopic connectivity. Relating the
model dynamics to experimental and clinical findings leads us to propose three
classes of dynamical mechanisms for the onset of focal seizures in a unified
framework. These three classes are: (i) globally induced focal seizures; (ii)
globally supported focal seizures; (iii) locally induced focal seizures. Using
model simulations we illustrate these onset mechanisms and show how the three
classes can be distinguished. Specifically, we find that although all focal
seizures typically appear to arise from localised tissue, the mechanisms of onset
could be due to either localised processes or processes on a larger spatial
scale. We conclude that although focal seizures might have different patient
specific aetiologies and electrographic signatures, our model suggests that
dynamically they can still be classified in a clinically useful way.
Additionally, this novel classification according to the dynamical mechanisms is
able to resolve some of the previously conflicting experimental and clinical
findings.
PMID- 25122456
TI - White blood cell-based detection of asymptomatic scrapie infection by ex vivo
assays.
AB - Prion transmission can occur by blood transfusion in human variant Creutzfeldt
Jakob disease and in experimental animal models, including sheep. Screening of
blood and its derivatives for the presence of prions became therefore a major
public health issue. As infectious titer in blood is reportedly low, highly
sensitive and robust methods are required to detect prions in blood and blood
derived products. The objectives of this study were to compare different methods-
in vitro, ex vivo and in vivo assays--to detect prion infectivity in cells
prepared from blood samples obtained from scrapie infected sheep at different
time points of the disease. Protein misfolding cyclic amplification (PMCA) and
bioassays in transgenic mice expressing the ovine prion protein were the most
efficient methods to identify infected animals at any time of the disease
(asymptomatic to terminally-ill stages). However scrapie cell and cerebellar
organotypic slice culture assays designed to replicate ovine prions in culture
also allowed detection of prion infectivity in blood cells from asymptomatic
sheep. These findings confirm that white blood cells are appropriate targets for
preclinical detection and introduce ex vivo tools to detect blood infectivity
during the asymptomatic stage of the disease.
PMID- 25122457
TI - Global decline in suitable habitat for Angiostrongylus ( = Parastrongylus)
cantonensis: the role of climate change.
AB - Climate change is implicated in the alteration of the ranges of species
worldwide. Such shifts in species distributions may introduce
parasites/pathogens, hosts, and vectors associated with disease to new areas. The
parasite Angiostrongylus ( = Parastrongylus) cantonensis is an invasive species
that causes eosinophilic meningitis in humans and neurological abnormalities in
domestic/wild animals. Although native to southeastern Asia, A. cantonensis has
now been reported from more than 30 countries worldwide. Given the health risks,
it is important to describe areas with potentially favorable climate for the
establishment of A. cantonensis, as well as areas where this pathogen might
become established in the future. We used the program Maxent to develop an
ecological niche model for A. cantonensis based on 86 localities obtained from
published literature. We then modeled areas of potential A. cantonensis
distribution as well as areas projected to have suitable climatic conditions
under four Representative Concentration Pathways (RCP) scenarios by the 2050s and
the 2070s. The best model contained three bioclimatic variables: mean diurnal
temperature range, minimum temperature of coldest month and precipitation of
warmest quarter. Potentially suitable habitat for A. cantonensis was located
worldwide in tropical and subtropical regions. Under all climate change RCP
scenarios, the center of the projected distribution shifted away from the equator
at a rate of 68-152 km per decade. However, the extent of areas with highly
suitable habitat (>50%) declined by 10.66-15.66% by the 2050s and 13.11-16.11% by
the 2070s. These results conflict with previous studies, which have generally
found that the prevalence of tropical pathogens will increase during the 21st
century. Moreover, it is likely that A. cantonensis will continue to expand its
current range in the near future due to introductions and host expansion, whereas
climate change will reduce the total geographic area of most suitable climatic
conditions during the coming decades.
PMID- 25122458
TI - De novo transcriptome assembly and comparative analysis of differentially
expressed genes in Prunus dulcis Mill. in response to freezing stress.
AB - Almond (Prunus dulcis Mill.), one of the most important nut crops, requires
chilling during winter to develop fruiting buds. However, early spring chilling
and late spring frost may damage the reproductive tissues leading to reduction in
the rate of productivity. Despite the importance of transcriptional changes and
regulation, little is known about the almond's transcriptome under the cold
stress conditions. In the current research, we used RNA-seq technique to study
the response of the reproductive tissues of almond (anther and ovary) to frost
stress. RNA sequencing resulted in more than 20 million reads from anther and
ovary tissues of almond, individually. About 40,000 contigs were assembled and
annotated de novo in each tissue. Profile of gene expression in ovary showed
significant alterations in 5,112 genes, whereas in anther 6,926 genes were
affected by freezing stress. Around two thousands of these genes were common
altered genes in both ovary and anther libraries. Gene ontology indicated the
involvement of differentially expressed (DE) genes, responding to freezing
stress, in metabolic and cellular processes. qRT-PCR analysis verified the
expression pattern of eight genes randomly selected from the DE genes. In
conclusion, the almond gene index assembled in this study and the reported DE
genes can provide great insights on responses of almond and other Prunus species
to abiotic stresses. The obtained results from current research would add to the
limited available information on almond and Rosaceae. Besides, the findings would
be very useful for comparative studies as the number of DE genes reported here is
much higher than that of any previous reports in this plant.
PMID- 25122460
TI - Effects of aging on osteogenic response and heterotopic ossification following
burn injury in mice.
AB - Heterotopic ossification (HO) is a common and debilitating complication of burns,
traumatic brain injuries, and musculoskeletal trauma and surgery. Although the
exact mechanism of ectopic bone formation is unknown, mesenchymal stem cells
(MSCs) capable of osteogenic differentiation are known to play an essential role.
Interestingly, the prevalence of HO in the elderly population is low despite the
high overall occurrence of musculoskeletal injury and orthopedic procedures. We
hypothesized that a lower osteogenicity of MSCs would be associated with blunted
HO formation in old compared with young mice. In vitro osteogenic differentiation
of adipose-derived MSCs from old (18-20 months) and young (6-8 weeks) C57/BL6
mice was assessed, with or without preceding burn injury. In vivo studies were
then performed using an Achilles tenotomy with concurrent burn injury HO model.
HO formation was quantified using MUCT scans, Raman spectroscopy, and histology.
MSCs from young mice had more in vitro bone formation, upregulation of bone
formation pathways, and higher activation of Smad and nuclear factor kappa B (NF
kappaB) signaling following burn injury. This effect was absent or blunted in
cells from old mice. In young mice, burn injury significantly increased HO
formation, NF-kappaB activation, and osteoclast activity at the tenotomy site.
This blunted, reactive osteogenic response in old mice follows trends seen
clinically and may be related to differences in the ability to mount acute
inflammatory responses. This unique characterization of HO and MSC osteogenic
differentiation following inflammatory insult establishes differences between age
populations and suggests potential pathways that could be targeted in the future
with therapeutics.
PMID- 25122461
TI - Prion propagation can occur in a prokaryote and requires the ClpB chaperone.
AB - Prions are self-propagating protein aggregates that are characteristically
transmissible. In mammals, the PrP protein can form a prion that causes the fatal
transmissible spongiform encephalopathies. Prions have also been uncovered in
fungi, where they act as heritable, protein-based genetic elements. We previously
showed that the yeast prion protein Sup35 can access the prion conformation in
Escherichia coli. Here, we demonstrate that E. coli can propagate the Sup35 prion
under conditions that do not permit its de novo formation. Furthermore, we show
that propagation requires the disaggregase activity of the ClpB chaperone. Prion
propagation in yeast requires Hsp104 (a ClpB ortholog), and prior studies have
come to conflicting conclusions about ClpB's ability to participate in this
process. Our demonstration of ClpB-dependent prion propagation in E. coli
suggests that the cytoplasmic milieu in general and a molecular machine in
particular are poised to support protein-based heredity in the bacterial domain
of life.
PMID- 25122463
TI - RLIMS-P: an online text-mining tool for literature-based extraction of protein
phosphorylation information.
AB - Protein phosphorylation is central to the regulation of most aspects of cell
function. Given its importance, it has been the subject of active research as
well as the focus of curation in several biological databases. We have developed
Rule-based Literature Mining System for protein Phosphorylation (RLIMS-P), an
online text-mining tool to help curators identify biomedical research articles
relevant to protein phosphorylation. The tool presents information on protein
kinases, substrates and phosphorylation sites automatically extracted from the
biomedical literature. The utility of the RLIMS-P Web site has been evaluated by
curators from Phospho.ELM, PhosphoGRID/BioGrid and Protein Ontology as part of
the BioCreative IV user interactive task (IAT). The system achieved F-scores of
0.76, 0.88 and 0.92 for the extraction of kinase, substrate and phosphorylation
sites, respectively, and a precision of 0.88 in the retrieval of relevant
phosphorylation literature. The system also received highly favorable feedback
from the curators in a user survey. Based on the curators' suggestions, the Web
site has been enhanced to improve its usability. In the RLIMS-P Web site,
phosphorylation information can be retrieved by PubMed IDs or keywords, with an
option for selecting targeted species. The result page displays a sortable table
with phosphorylation information. The text evidence page displays the abstract
with color-coded entity mentions and includes links to UniProtKB entries via
normalization, i.e., the linking of entity mentions to database identifiers,
facilitated by the GenNorm tool and by the links to the bibliography in UniProt.
Log in and editing capabilities are offered to any user interested in
contributing to the validation of RLIMS-P results. Retrieved phosphorylation
information can also be downloaded in CSV format and the text evidence in the
BioC format. RLIMS-P is freely available. DATABASE URL:
http://www.proteininformationresource.org/rlimsp/
PMID- 25122465
TI - Development of the Cell Population in the Brain White Matter of Young Children.
AB - While brain gray matter is primarily associated with sensorimotor processing and
cognition, white matter modulates the distribution of action potentials,
coordinates communication between different brain regions, and acts as a relay
for input/output signals. Previous studies have described morphological changes
in gray and white matter during childhood and adolescence, which are consistent
with cellular genesis and maturation, but corresponding events in infants are
poorly documented. In the present study, we estimated the total number of cells
(neurons, oligodendrocytes, astrocytes, and microglia) in the cerebral white
matter of 9 infants aged 0-33 months, using design-based stereological methods to
obtain quantitative data about brain development. There were linear increases
with age in the numbers of oligodendrocytes (7-28 billion) and astrocytes (1.5
6.7 billion) during the first 3 years of life, thus attaining two-thirds of the
corresponding numbers in adults. The numbers of neurons (0.7 billion) and
microglia (0.2 billion) in the white matter did not increase during the first 3
years of life, but showed large biological variation.
PMID- 25122462
TI - Epsin deficiency impairs endocytosis by stalling the actin-dependent invagination
of endocytic clathrin-coated pits.
AB - Epsin is an evolutionarily conserved endocytic clathrin adaptor whose most
critical function(s) in clathrin coat dynamics remain(s) elusive. To elucidate
such function(s), we generated embryonic fibroblasts from conditional epsin
triple KO mice. Triple KO cells displayed a dramatic cell division defect.
Additionally, a robust impairment in clathrin-mediated endocytosis was observed,
with an accumulation of early and U-shaped pits. This defect correlated with a
perturbation of the coupling between the clathrin coat and the actin
cytoskeleton, which we confirmed in a cell-free assay of endocytosis. Our results
indicate that a key evolutionary conserved function of epsin, in addition to
other roles that include, as we show here, a low affinity interaction with
SNAREs, is to help generate the force that leads to invagination and then fission
of clathrin-coated pits.
PMID- 25122464
TI - Lower intensified target LDL-c level of statin therapy results in a higher risk
of incident diabetes: a meta-analysis.
AB - BACKGROUND: A recent meta-analysis has reported that intensive-dose statin drug
increases the risk of incident diabetes. However, doubling of the statin dose
generates only a further 6% decrease in low-density lipoprotein cholesterol (LDL
c) on average. This study aimed to determine whether statin therapy with lower
intensive-target LDL-c level contributes to higher risk of new-onset diabetes.
METHODS: Medline, Embase, and the Cochrane Central Register of Controlled Trials
were searched for randomized controlled endpoint trials of statins conducted from
1966 to 2012. We included trials with more than 1000 participants who were
followed up for at least 2 years. The included trials were stratified by the
target LDL-c level. I2 statistic was used to measure heterogeneity between
trials. We further calculated risk estimates with random-effect meta-analysis.
Meta-regression was used to identify the potential risk factors of statin-induced
diabetes. RESULTS: Fourteen trials with a total of 95 102 non-diabetic
participants were included. The risks elevated by 33% [odds ratio (OR) = 1.33;
95% confidence interval (CI) 1.14-1.56; I(2) = 7.7%] and 16% (OR = 1.16; 95% CI
1.06-1.28; I(2)= 0.0%) when the intensified target LDL-c levels were <= 1.8
mmol/L and 1.8-2.59 mmol/L, respectively. The risk of incident diabetes did not
increase when the target LDL-c level was >= 2.59 mmol/L. Apart from age, female,
and baseline level of total cholesterol, meta-regression analysis showed that the
target and baseline levels of LDL-c and relative LDL-c reduction were predictors
of statin-induced diabetes. CONCLUSION: A lower intensified target LDL-c level of
statin therapy resulted in a higher risk of incident diabetes.
PMID- 25122466
TI - The Fault Lies on the Other Side: Altered Brain Functional Connectivity in
Psychiatric Disorders is Mainly Caused by Counterpart Regions in the Opposite
Hemisphere.
AB - Many psychiatric disorders are associated with abnormal resting-state functional
connectivity between pairs of brain regions, although it remains unclear whether
the fault resides within the pair of regions themselves or other regions
connected to them. Identifying the source of dysfunction is crucial for
understanding the etiology of different disorders. Using pathway- and network
based techniques to analyze resting-state functional magnetic imaging data from a
large population of patients with attention deficit hyperactivity disorder (239
patients, 251 controls), major depression (39 patients, 37 controls), and
schizophrenia (69 patients, 62 controls), we show for the first time that only
network-based cross-correlation identifies significant functional connectivity
changes in all 3 disorders which survive correction. This demonstrates that the
primary source of dysfunction resides not in the regional pairs themselves but in
their external connections. Combining pathway and network-based functional
connectivity analysis, we established that, in all 3 disorders, the counterparts
of pairs of regions in the opposite hemisphere contribute 60-76% to altered
functional connectivity, compared with only 17-21% from the regions themselves.
Thus, a transdiagnostic feature is of abnormal functional connectivity between
brain regions produced via their contralateral counterparts. Our results
demonstrate an important role for contralateral counterpart regions in
contributing to altered regional connectivity in psychiatric disorders.
PMID- 25122467
TI - Common myna roosts are not recruitment centres.
AB - We studied communal roosting in the Common Myna (Acridotheres tristis) in the
light of the recruitment centre hypothesis and predation at the roost. The number
and sizes of flocks departing from and arriving at focal roosts were recorded
over a two year period. We also recorded the sizes and behaviour of foraging
flocks. We found that flock sizes of birds departing from roosts at sunrise were
larger than those at the feeding site, suggesting that there was no recruitment
from the roosts. Flocks entering the roosts during sunset were larger on average
than those leaving the following sunrise, suggesting no consolidation of flocks
in the morning. Flocks entering the roosts at sunset were also larger on average
than those that had left that sunrise, although there was no recruitment at the
feeding site. There was no effect of group size on the proportion of time spent
feeding. Contrary to expectation, single birds showed lower apparent vigilance
than birds that foraged in pairs or groups, possibly due to scrounging tactics
being used in the presence of feeding companions. Thus, the recruitment centre
hypothesis did not hold in our study population of mynas. Predation at dawn and
dusk were also not important to communal roosting: predators near the roosts did
not result in larger flocks, and resulted in larger durations of
arrival/departure contrary to expectation. Since flock sizes were smallest at the
feeding site and larger in the evening than in the morning, but did not coincide
with predator activity, information transfer unrelated to food (such as breeding
opportunities) may possibly give rise to the evening aggregations.
PMID- 25122468
TI - Education on hygiene and sanitation is the need of the hour in India.
PMID- 25122469
TI - Effects of a post-deworming health hygiene education intervention on absenteeism
in school-age children of the Peruvian Amazon.
AB - Soil-transmitted helminth (STH) infections are a leading cause of disability and
disease burden in school-age children of worm-endemic regions. Their effect on
school absenteeism, however, remains unclear. The World Health Organization
currently recommends delivering mass deworming and health hygiene education
through school-based programs, in an effort to control STH-related morbidity. In
this cluster-RCT, the impact of a health hygiene education intervention on
absenteeism was measured. From April to June 2010, all Grade 5 students at 18
schools in a worm-endemic region of the Peruvian Amazon were dewormed.
Immediately following deworming, nine schools were randomly assigned to the
intervention arm of the trial using a matched-pair design. The Grade 5 students
attending intervention schools (N = 517) received four months of health hygiene
education aimed at increasing knowledge of STH prevention. Grade 5 students from
the other nine schools (N = 571) served as controls. Absenteeism was measured
daily through teachers' attendance logs. After four months of follow-up, overall
absenteeism rates at intervention and control schools were not statistically
significantly different. However, post-trial non-randomized analyses have shown
that students with moderate-to-heavy Ascaris infections and light hookworm
infections four months after deworming had, respectively, missed 2.4% (95% CI:
0.1%, 4.7%) and 4.6% (95% CI: 1.9%, 7.4%) more schooldays during the follow-up
period than their uninfected counterparts. These results provide empirical
evidence of a direct effect of STH infections on absenteeism in school-age
children.
PMID- 25122470
TI - Identification of suitable reference genes for gene expression studies of
shoulder instability.
AB - Shoulder instability is a common shoulder injury, and patients present with
plastic deformation of the glenohumeral capsule. Gene expression analysis may be
a useful tool for increasing the general understanding of capsule deformation,
and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) has
become an effective method for such studies. Although RT-qPCR is highly sensitive
and specific, it requires the use of suitable reference genes for data
normalization to guarantee meaningful and reproducible results. In the present
study, we evaluated the suitability of a set of reference genes using samples
from the glenohumeral capsules of individuals with and without shoulder
instability. We analyzed the expression of six commonly used reference genes
(ACTB, B2M, GAPDH, HPRT1, TBP and TFRC) in the antero-inferior, antero-superior
and posterior portions of the glenohumeral capsules of cases and controls. The
stability of the candidate reference gene expression was determined using four
software packages: NormFinder, geNorm, BestKeeper and DataAssist. Overall, HPRT1
was the best single reference gene, and HPRT1 and B2M composed the best pair of
reference genes from different analysis groups, including simultaneous analysis
of all tissue samples. GenEx software was used to identify the optimal number of
reference genes to be used for normalization and demonstrated that the
accumulated standard deviation resulting from the use of 2 reference genes was
similar to that resulting from the use of 3 or more reference genes. To identify
the optimal combination of reference genes, we evaluated the expression of
COL1A1. Although the use of different reference gene combinations yielded
variable normalized quantities, the relative quantities within sample groups were
similar and confirmed that no obvious differences were observed when using 2, 3
or 4 reference genes. Consequently, the use of 2 stable reference genes for
normalization, especially HPRT1 and B2M, is a reliable method for evaluating gene
expression by RT-qPCR.
PMID- 25122471
TI - EVM005: an ectromelia-encoded protein with dual roles in NF-kappaB inhibition and
virulence.
AB - Poxviruses contain large dsDNA genomes encoding numerous open reading frames that
manipulate cellular signalling pathways and interfere with the host immune
response. The NF-kappaB signalling cascade is an important mediator of innate
immunity and inflammation, and is tightly regulated by ubiquitination at several
key points. A critical step in NF-kappaB activation is the ubiquitination and
degradation of the inhibitor of kappaB (IkappaBalpha), by the cellular SCFbeta
TRCP ubiquitin ligase complex. We show here that upon stimulation with TNFalpha
or IL-1beta, Orthopoxvirus-infected cells displayed an accumulation of
phosphorylated IkappaBalpha, indicating that NF-kappaB activation was inhibited
during poxvirus infection. Ectromelia virus is the causative agent of lethal
mousepox, a natural disease that is fatal in mice. Previously, we identified a
family of four ectromelia virus genes (EVM002, EVM005, EVM154 and EVM165) that
contain N-terminal ankyrin repeats and C-terminal F-box domains that interact
with the cellular SCF ubiquitin ligase complex. Since degradation of IkappaBalpha
is catalyzed by the SCFbeta-TRCP ubiquitin ligase, we investigated the role of
the ectromelia virus ankyrin/F-box protein, EVM005, in the regulation of NF
kappaB. Expression of Flag-EVM005 inhibited both TNFalpha- and IL-1beta
stimulated IkappaBalpha degradation and p65 nuclear translocation. Inhibition of
the NF-kappaB pathway by EVM005 was dependent on the F-box domain, and
interaction with the SCF complex. Additionally, ectromelia virus devoid of EVM005
was shown to inhibit NF-kappaB activation, despite lacking the EVM005 open
reading frame. Finally, ectromelia virus devoid of EVM005 was attenuated in both
A/NCR and C57BL/6 mouse models, indicating that EVM005 is required for virulence
and immune regulation in vivo.
PMID- 25122473
TI - The impact of herbicide-resistant rice technology on phenotypic diversity and
population structure of United States weedy rice.
AB - The use of herbicide-resistant (HR) Clearfield rice (Oryza sativa) to control
weedy rice has increased in the past 12 years to constitute about 60% of rice
acreage in Arkansas, where most U.S. rice is grown. To assess the impact of HR
cultivated rice on the herbicide resistance and population structure of weedy
rice, weedy samples were collected from commercial fields with a history of
Clearfield rice. Panicles from each weedy type were harvested and tested for
resistance to imazethapyr. The majority of plants sampled had at least 20%
resistant offspring. These resistant weeds were 97 to 199 cm tall and initiated
flowering from 78 to 128 d, generally later than recorded for accessions
collected prior to the widespread use of Clearfield rice (i.e. historical
accessions). Whereas the majority (70%) of historical accessions had straw
colored hulls, only 30% of contemporary HR weedy rice had straw-colored hulls.
Analysis of genotyping-by-sequencing data showed that HR weeds were not
genetically structured according to hull color, whereas historical weedy rice was
separated into straw-hull and black-hull populations. A significant portion of
the local rice crop genome was introgressed into HR weedy rice, which was rare in
historical weedy accessions. Admixture analyses showed that HR weeds tend to
possess crop haplotypes in the portion of chromosome 2 containing the
ACETOLACTATE SYNTHASE gene, which confers herbicide resistance to Clearfield
rice. Thus, U.S. HR weedy rice is a distinct population relative to historical
weedy rice and shows modifications in morphology and phenology that are relevant
to weed management.
PMID- 25122474
TI - Multiple sclerosis: progression rate and severity in a multicenter cohort from
Algeria.
PMID- 25122472
TI - Label-free protein quantification for plant Golgi protein localization and
abundance.
AB - The proteomic composition of the Arabidopsis (Arabidopsis thaliana) Golgi
apparatus is currently reasonably well documented; however, little is known about
the relative abundances between different proteins within this compartment.
Accurate quantitative information of Golgi resident proteins is of great
importance: it facilitates a better understanding of the biochemical processes
that take place within this organelle, especially those of different
polysaccharide synthesis pathways. Golgi resident proteins are challenging to
quantify because the abundance of this organelle is relatively low within the
cell. In this study, an organelle fractionation approach targeting the Golgi
apparatus was combined with a label-free quantitative mass spectrometry (data
independent acquisition method using ion mobility separation known as LC-IMS
MS(E) [or HDMS(E)]) to simultaneously localize proteins to the Golgi apparatus
and assess their relative quantity. In total, 102 Golgi-localized proteins were
quantified. These data show that organelle fractionation in conjunction with
label-free quantitative mass spectrometry is a powerful and relatively simple
tool to access protein organelle localization and their relative abundances. The
findings presented open a unique view on the organization of the plant Golgi
apparatus, leading toward unique hypotheses centered on the biochemical processes
of this organelle.
PMID- 25122475
TI - The central role of mitochondria in axonal degeneration in multiple sclerosis.
AB - Neurodegeneration in multiple sclerosis (MS) is related to inflammation and
demyelination. In acute MS lesions and experimental autoimmune encephalomyelitis
focal immune attacks damage axons by injuring axonal mitochondria. In progressive
MS, however, axonal damage occurs in chronically demyelinated regions, myelinated
regions and also at the active edge of slowly expanding chronic lesions. How
axonal energy failure occurs in progressive MS is incompletely understood. Recent
studies show that oligodendrocytes supply lactate to myelinated axons as a
metabolic substrate for mitochondria to generate ATP, a process which will be
altered upon demyelination. In addition, a number of studies have identified
mitochondrial abnormalities within neuronal cell bodies in progressive MS,
leading to a deficiency of mitochondrial respiratory chain complexes or enzymes.
Here, we summarise the mitochondrial abnormalities evident within neurons and
discuss how these grey matter mitochondrial abnormalities may increase the
vulnerability of axons to degeneration in progressive MS. Although neuronal
mitochondrial abnormalities will culminate in axonal degeneration, understanding
the different contributions of mitochondria to the degeneration of myelinated and
demyelinated axons is an important step towards identifying potential therapeutic
targets for progressive MS.
PMID- 25122476
TI - Non-random escape pathways from a broadly neutralizing human monoclonal antibody
map to a highly conserved region on the hepatitis C virus E2 glycoprotein
encompassing amino acids 412-423.
AB - A challenge for hepatitis C virus (HCV) vaccine development is to define epitopes
that are able to elicit protective antibodies against this highly diverse virus.
The E2 glycoprotein region located at residues 412-423 is conserved and
antibodies to 412-423 have broadly neutralizing activities. However, an adaptive
mutation, N417S, is associated with a glycan shift in a variant that cannot be
neutralized by a murine but by human monoclonal antibodies (HMAbs) against 412
423. To determine whether HCV escapes from these antibodies, we analyzed variants
that emerged when cell culture infectious HCV virions (HCVcc) were passaged under
increasing concentrations of a specific HMAb, HC33.1. Multiple nonrandom escape
pathways were identified. Two pathways occurred in the context of an N-glycan
shift mutation at N417T. At low antibody concentrations, substitutions of two
residues outside of the epitope, N434D and K610R, led to variants having improved
in vitro viral fitness and reduced sensitivity to HC33.1 binding and
neutralization. At moderate concentrations, a S419N mutation occurred within 412
423 in escape variants that have greatly reduced sensitivity to HC33.1 but
compromised viral fitness. Importantly, the variants generated from these
pathways differed in their stability. N434D and K610R-associated variants were
stable and became dominant as the virions were passaged. The S419N mutation
reverted back to N419S when immune pressure was reduced by removing HC33.1. At
high antibody concentrations, a mutation at L413I was observed in variants that
were resistant to HC33.1 neutralization. Collectively, the combination of
multiple escape pathways enabled the virus to persist under a wide range of
antibody concentrations. Moreover, these findings pose a different challenge to
vaccine development beyond the identification of highly conserved epitopes. It
will be necessary for a vaccine to induce high potency antibodies that prevent
the formation of escape variants, which can co-exist with lower potency or levels
of neutralizing activities.
PMID- 25122477
TI - Surface physicochemistry and ionic strength affects eDNA's role in bacterial
adhesion to abiotic surfaces.
AB - Extracellular DNA (eDNA) is an important structural component of biofilms formed
by many bacteria, but few reports have focused on its role in initial cell
adhesion. The aim of this study was to investigate the role of eDNA in bacterial
adhesion to abiotic surfaces, and determine to which extent eDNA-mediated
adhesion depends on the physicochemical properties of the surface and surrounding
liquid. We investigated eDNA alteration of cell surface hydrophobicity and zeta
potential, and subsequently quantified the effect of eDNA on the adhesion of
Staphylococcus xylosus to glass surfaces functionalised with different
chemistries resulting in variable hydrophobicity and charge. Cell adhesion
experiments were carried out at three different ionic strengths. Removal of eDNA
from S. xylosus cells by DNase treatment did not alter the zeta potential, but
rendered the cells more hydrophilic. DNase treatment impaired adhesion of cells
to glass surfaces, but the adhesive properties of S. xylosus were regained within
30 minutes if DNase was not continuously present, implying a continuous release
of eDNA in the culture. Removal of eDNA lowered the adhesion of S. xylosus to all
surfaces chemistries tested, but not at all ionic strengths. No effect was seen
on glass surfaces and carboxyl-functionalised surfaces at high ionic strength,
and a reverse effect occurred on amine-functionalised surfaces at low ionic
strength. However, eDNA promoted adhesion of cells to hydrophobic surfaces
irrespective of the ionic strength. The adhesive properties of eDNA in mediating
initial adhesion of S. xylosus is thus highly versatile, but also dependent on
the physicochemical properties of the surface and ionic strength of the
surrounding medium.
PMID- 25122480
TI - Attorneys general from 29 US states urge tougher e-cigarette regulations.
PMID- 25122479
TI - Optimal behavioral hierarchy.
AB - Human behavior has long been recognized to display hierarchical structure:
actions fit together into subtasks, which cohere into extended goal-directed
activities. Arranging actions hierarchically has well established benefits,
allowing behaviors to be represented efficiently by the brain, and allowing
solutions to new tasks to be discovered easily. However, these payoffs depend on
the particular way in which actions are organized into a hierarchy, the specific
way in which tasks are carved up into subtasks. We provide a mathematical account
for what makes some hierarchies better than others, an account that allows an
optimal hierarchy to be identified for any set of tasks. We then present results
from four behavioral experiments, suggesting that human learners spontaneously
discover optimal action hierarchies.
PMID- 25122478
TI - Epidermal growth factor stimulates nuclear factor-kappaB activation and heme
oxygenase-1 expression via c-Src, NADPH oxidase, PI3K, and Akt in human colon
cancer cells.
AB - Previous report showed that epidermal growth factor (EGF) promotes tumor
progression. Several studies demonstrated that growth factors can induce heme
oxygenase (HO)-1 expression, protect against cellular injury and cancer cell
proliferation. In this study, we investigated the involvement of the c-Src, NADPH
oxidase, reactive oxygen species (ROS), PI3K/Akt, and NF-kappaB signaling
pathways in EGF-induced HO-1 expression in human HT-29 colon cancer cells.
Treatment of HT-29 cells with EGF caused HO-1 to be expressed in concentration-
and time-dependent manners. Treatment of HT-29 cells with AG1478 (an EGF receptor
(EGFR) inhibitor), small interfering RNA of EGFR (EGFR siRNA), a dominant
negative mutant of c-Src (c-Src DN), DPI (an NADPH oxidase inhibitor),
glutathione (an ROS inhibitor), LY294002 (a PI3K inhibitor), and an Akt DN
inhibited EGF-induced HO-1 expression. Stimulation of cells with EGF caused an
increase in c-Src phosphorylation at Tyr406 in a time-dependent manner. Treatment
of HT-29 cells with EGF induced an increase in p47(phox) translocation from the
cytosol to membranes. The EGF-induced ROS production was inhibited by DPI.
Stimulation of cells with EGF resulted in an increase in Akt phosphorylation at
Ser473, which was inhibited by c-Src DN, DPI, and LY 294002. Moreover, treatment
of HT-29 cells with a dominant negative mutant of IkappaB (IkappaBalphaM)
inhibited EGF-induced HO-1 expression. Stimulation of cells with EGF induced p65
translocation from the cytosol to nuclei. Treatment of HT-29 cells with EGF
induced an increase in kappaB-luciferase activity, which was inhibited by a c-Src
DN, LY 294002, and an Akt DN. Furthermore, EGF-induced colon cancer cell
proliferation was inhibited by Sn(IV)protoporphyrin-IX (snPP, an HO-1 inhibitor).
Taken together, these results suggest that the c-Src, NADPH oxidase, PI3K, and
Akt signaling pathways play important roles in EGF-induced NF-kappaB activation
and HO-1 expression in HT-29 cells. Moreover, overexpression of HO-1 mediates EGF
induced colon cancer cell proliferation.
PMID- 25122481
TI - Interactions of Rice tungro bacilliform pararetrovirus and its protein P4 with
plant RNA-silencing machinery.
AB - Small interfering RNA (siRNA)-directed gene silencing plays a major role in
antiviral defense. Virus-derived siRNAs inhibit viral replication in infected
cells and potentially move to neighboring cells, immunizing them from incoming
virus. Viruses have evolved various ways to evade and suppress siRNA production
or action. Here, we show that 21-, 22-, and 24-nucleotide (nt) viral siRNAs
together constitute up to 19% of total small RNA population of Oryza sativa
plants infected with Rice tungro bacilliform virus (RTBV) and cover both strands
of the RTBV DNA genome. However, viral siRNA hotspots are restricted to a short
noncoding region between transcription and reverse-transcription start sites.
This region generates double-stranded RNA (dsRNA) precursors of siRNAs and, in
pregenomic RNA, forms a stable secondary structure likely inaccessible to siRNA
directed cleavage. In transient assays, RTBV protein P4 suppressed cell-to-cell
spread of silencing but enhanced cell-autonomous silencing, which correlated with
reduced 21-nt siRNA levels and increased 22-nt siRNA levels. Our findings imply
that RTBV generates decoy dsRNA that restricts siRNA production to the structured
noncoding region and thereby protects other regions of the viral genome from
repressive action of siRNAs, while the viral protein P4 interferes with cell-to
cell spread of antiviral silencing.
PMID- 25122482
TI - The novel monocot-specific 9-lipoxygenase ZmLOX12 is required to mount an
effective jasmonate-mediated defense against Fusarium verticillioides in maize.
AB - Fusarium verticillioides is a major limiting factor for maize production due to
ear and stalk rot and the contamination of seed with the carcinogenic mycotoxin
fumonisin. While lipoxygenase (LOX)-derived oxylipins have been implicated in
defense against diverse pathogens, their function in maize resistance against F.
verticillioides is poorly understood. Here, we functionally characterized a novel
maize 9-LOX gene, ZmLOX12. This gene is distantly related to known dicot LOX
genes, with closest homologs found exclusively in other monocot species. ZmLOX12
is predominantly expressed in mesocotyls in which it is strongly induced in
response to F. verticillioides infection. The Mutator transposon-insertional
lox12-1 mutant is more susceptible to F. verticillioides colonization of
mesocotyls, stalks, and kernels. The infected mutant kernels accumulate a
significantly greater amount of the mycotoxin fumonisin. Reduced resistance to
the pathogen is accompanied by diminished levels of the jasmonic acid (JA)
precursor 12-oxo phytodienoic acid, JA-isoleucine, and expression of jasmonate
biosynthetic genes. Supporting the strong defense role of jasmonates, the JA
deficient opr7 opr8 double mutant displayed complete lack of immunity to F.
verticillioides. Unexpectedly, the more susceptible lox12 mutant accumulated
higher levels of kauralexins, suggesting that F. verticillioides is tolerant to
this group of antimicrobial phytoalexins. This study demonstrates that this
unique monocot-specific 9-LOX plays a key role in defense against F.
verticillioides in diverse maize tissues and provides genetic evidence that JA is
the major defense hormone against this pathogen.
PMID- 25122483
TI - Nucleoporin 75 is involved in the ethylene-mediated production of phytoalexin for
the resistance of Nicotiana benthamiana to Phytophthora infestans.
AB - Mature Nicotiana benthamiana shows stable resistance to the oomycete pathogen
Phytophthora infestans. Induction of phytoalexin (capsidiol) production is
essential for the resistance, which is upregulated via a mitogen-activated
protein kinase (MAPK) cascade (NbMEK2-WIPK/SIPK) followed by ethylene signaling.
In this study, NbNup75 (encodes a nuclear pore protein Nucleoporin75) was
identified as an essential gene for resistance of N. benthamiana to P. infestans.
In NbNup75-silenced plants, initial events of elicitor-induced responses such as
phosphorylation of MAPK and expression of defense-related genes were not
affected, whereas induction of later defense responses such as capsidiol
production and cell death induction was suppressed or delayed. Ethylene
production induced by either INF1 or NbMEK2 was reduced in NbNup75-silenced
plants, whereas the expression of NbEAS (a gene for capsidiol biosynthesis)
induced by ethylene was not affected, indicating that Nup75 is required for the
induction of ethylene production but not for ethylene signaling. Given that
nuclear accumulation of polyA RNA was increased in NbNup75-silenced plants,
efficient export of mRNA from nuclei via nuclear pores would be important for the
timely upregulation of defense responses. Collectively, Nup75 is involved in the
induction of a later stage of defense responses, including the ethylene-mediated
production of phytoalexin for the resistance of N. benthamiana to P. infestans.
PMID- 25122484
TI - Endoscopic balloon dilatation as an effective treatment for lower and upper
benign gastrointestinal system anastomotic stenosis.
AB - OBJECTIVE: Endoscopic balloon dilatation (EBD) is currently accepted as an
effective, safe, and first-line treatment of postoperative benign
gastrointestinal anastomosis stenosis (BGAS); however, a limited number of
publications on the subject exist in the literature. The aim of the study was to
retrospectively evaluate the efficiency of endoscopic dilatation in patients with
postoperative intestinal anastomotic stenoses at a single surgical center.
METHODS: Patients with postoperative BGAS treated by EBD at our institution from
February 2008 to 2012 were included. The dilatations were all performed using
through-the-scope balloons. The balloon was introduced into the stricture using a
guidewire under radiologic guidance. Each dilatation session consisted of 2 to 3
two-minute multistep inflations of the balloon until adequate dilatation was
achieved. RESULTS: Of the 48 patients included in the study, 44 patients (91.7%)
fully recovered and 4 (8.3%) did not respond to treatment. The mean follow-up
period was 24 months (range, 3 to 57 mo). Four patients who did not respond to
the procedure were treated surgically. Two patients (4.1%) with intestinal
perforation during EBD were treated conservatively with a stent. CONCLUSIONS: EBD
has a low rate of complications and a high success rate, is well tolerated, and
avoids further surgical procedures for BGAS. Therefore, EBD should be the first
choice of treatment for postoperative anastomotic stenoses.
PMID- 25122485
TI - Totally laparoscopic cyst excision and Roux-en-Y hepaticojejunostomy for
choledochal cyst in adults: a single-institute experience of 5 years.
AB - PURPOSE: The present study aimed to describe the authors' experience and the
intermediate-term outcome for totally laparoscopic choledochal cyst excision and
Roux-en-Y hepatoenterostomy at a single center in a 5-year period. METHODS: We
retrospectively analyzed the clinical data of totally laparoscopic choledochal
cyst excision and Roux-en-Y hepatoenterostomy on 31 adult patients from January
2009 to November 2013. RESULTS: Thirty-one cases successfully underwent totally
laparoscopic choledochal cyst excision laparoscopy and Roux-en-Y
hepatoenterostomy. The operation time varied from 200 to 360 minutes. The
intraoperative blood loss was 50 to 210 mL. The patients passed flatus in 3.0 +/-
1.3 days. The mean time interval to resume oral intake from the time of surgery
was 3.8 +/- 1.4 days. The duration of postoperative intravenous fluids was 4 to
11 days. Postoperative ambulation varied from 2 to 4 days. The duration of
hospital stay was 4 to 13 days. Follow-up observations lasted 3 to 59 months and
complications were noted in 4 patients. Of these patients, 1 patient suffered
postoperative respiratory tract infection, 1 patient had an episode of adhesive
small bowel obstruction, biliary leakage occurred in 1 patient, and 1 patient
developed an anastomotic stoma stricture and cholangitis. There were no
perioperative deaths. CONCLUSIONS: Totally laparoscopic cyst excision and Roux-en
Y hepaticojejunostomy is a safe, efficacious, and minimally invasive procedure
for the most instances of adult choledochal cyst. The key of success is skilled
laparoscopic skills, good team cooperation, and stapler anastomosis.
PMID- 25122488
TI - Extended phase-correlated rescanning irradiation to improve dose homogeneity in
carbon-ion beam liver treatment.
AB - We previously reported that an adequate number of simple layered phase-correlated
rescanning (PCR) irradiations improve dose conformation to a moving target.
However, if PCR is not completed within a single gating window due to the
particular irradiation specifications selected in advance and/or layer size, the
iso-energy layer is completed using next gating window, and the effect of
rescanning is effectively nullified. To solve this problem, we developed extended
PCR irradiation. Extended PCR is conceptually based on simple PCR. It differs in
that the dose rate is adjusted to irradiate the number of rescans within multiple
gating windows when simple PCR is not finished within a single gating window.
This process is repeated until the total prescribed dose is given. Here, 4DCT
imaging was performed under free-breathing conditions in 10 patients with
hepatocellular carcinoma. 4D dose distributions for a single field approach were
performed with simple PCR and extended PCR using 4DCT. A total dose of 11.25
Gy(RBE) was administered to the field-specific target volume. The number of
rescans was changed from 1 to 10. Respiratory gating of a 30% duty cycle around
exhalation was applied. Dose assessment metrics (CTV-D95, CTV-Dmin, CTV-Dmax)
with PCR improved with an increasing number of rescans, and largely plateaued at
five or more rescans. Minimum D95 and Dmin values, and maximum Dmax and HI values
fluctuated at odd and even numbers of rescans. Extended PCR improved all dose
assessment metrics whereas PCR did not. Values with extended PCR were mostly
constant with three or more rescans, or in other words independent of the number
of rescans. Extended PCR improved dose conformation to a moving target with
greater efficacy than simple PCR when more than two gating windows were
necessary. Extended PCR can be applied to irradiation machines having a low
maximum dose rate.
PMID- 25122487
TI - Global gene expression profiling in three tumor cell lines subjected to
experimental cycling and chronic hypoxia.
AB - Hypoxia is one of the most important features of the tumor microenvironment,
exerting an adverse effect on tumor aggressiveness and patient prognosis. Two
types of hypoxia may occur within the tumor mass, chronic (prolonged) and cycling
(transient, intermittent) hypoxia. Cycling hypoxia has been shown to induce
aggressive tumor cell phenotype and radioresistance more significantly than
chronic hypoxia, though little is known about the molecular mechanisms underlying
this phenomenon. The aim of this study was to delineate the molecular response to
both types of hypoxia induced experimentally in tumor cells, with a focus on
cycling hypoxia. We analyzed in vitro gene expression profile in three human
cancer cell lines (melanoma, ovarian cancer, and prostate cancer) exposed to
experimental chronic or transient hypoxia conditions. As expected, the cell-type
specific variability in response to hypoxia was significant. However, the
expression of 240 probe sets was altered in all 3 cell lines. We found that gene
expression profiles induced by both types of hypoxia were qualitatively similar
and strongly depend on the cell type. Cycling hypoxia altered the expression of
fewer genes than chronic hypoxia (6,132 vs. 8,635 probe sets, FDR adjusted
p<0.05), and with lower fold changes. However, the expression of some of these
genes was significantly more affected by cycling hypoxia than by prolonged
hypoxia, such as IL8, PLAU, and epidermal growth factor (EGF) pathway-related
genes (AREG, HBEGF, and EPHA2). These transcripts were, in most cases, validated
by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Our
results indicate that experimental cycling hypoxia exerts similar, although less
intense effects, on the examined cancer cell lines than its chronic counterpart.
Nonetheless, we identified genes and molecular pathways that seem to be
preferentially regulated by cyclic hypoxia.
PMID- 25122489
TI - A commentary on the disparate perspectives of clinical microbiologists and
surgeons: ad hoc antimicrobial use.
AB - Prosthetic joints and other orthopedic implants have improved quality of life for
patients world-wide and the use of such devices is increasing. However, while
infection rates subsequent to associated surgery are relatively low (<3%), the
consequences of incidence are considerable, encompassing morbidity (including
amputation) and mortality in addition to significant social and economic costs.
Emphasis, therefore, has been placed on mitigating microbial risk, with clinical
microbiologists and surgeons utilizing rapidly evolving molecular laboratory
techniques in detection and diagnosis of infection, which still occurs despite
sophisticated patient management. Multidisciplinary approaches are regularly
adopted to achieve this. In this commentary, we describe an unusual case of
Actinomyces infection in total hip arthroplasty and, in that context, describe
the perspectives of the clinical microbiology and surgical teams and how they
contrasted. More specifically, this case demonstrates an ad hoc approach to
structured eradication of biofilms and intracellular bacteria related to
biomaterials, as reflected in early usage of linezolid. This is a complex topic
and, as described in this case, such accelerated treatment can be effective. This
commentary focuses on the merits of such inadvisable use of potent antimicrobials
amid the risk of diminishing valuable antimicrobial efficacy, albeit resulting in
desirable patient outcomes.
PMID- 25122490
TI - Human NR5A1/SF-1 mutations show decreased activity on BDNF (brain-derived
neurotrophic factor), an important regulator of energy balance: testing impact of
novel SF-1 mutations beyond steroidogenesis.
AB - CONTEXT: Human NR5A1/SF-1 mutations cause 46,XY disorder of sex development (DSD)
with broad phenotypic variability, and rarely cause adrenal insufficiency
although SF-1 is an important transcription factor for many genes involved in
steroidogenesis. In addition, the Sf-1 knockout mouse develops obesity with age.
Obesity might be mediated through Sf-1 regulating activity of brain-derived
neurotrophic factor (BDNF), an important regulator of energy balance in the
ventromedial hypothalamus. OBJECTIVE: To characterize novel SF-1 gene variants in
4 families, clinical, genetic and functional studies were performed with respect
to steroidogenesis and energy balance. PATIENTS: 5 patients with 46,XY DSD were
found to harbor NR5A1/SF-1 mutations including 2 novel variations. One patient
harboring a novel mutation also suffered from adrenal insufficiency. METHODS: SF
1 mutations were studied in cell systems (HEK293, JEG3) for impact on
transcription of genes involved in steroidogenesis (CYP11A1, CYP17A1, HSD3B2) and
in energy balance (BDNF). BDNF regulation by SF-1 was studied by promoter assays
(JEG3). RESULTS: Two novel NR5A1/SF-1 mutations (Glu7Stop, His408Profs*159) were
confirmed. Glu7Stop is the 4th reported SF-1 mutation causing DSD and adrenal
insufficiency. In vitro studies revealed that transcription of the BDNF gene is
regulated by SF-1, and that mutant SF-1 decreased BDNF promoter activation
(similar to steroid enzyme promoters). However, clinical data from 16 subjects
carrying SF-1 mutations showed normal birth weight and BMI. CONCLUSIONS: Glu7Stop
and His408Profs*159 are novel SF-1 mutations identified in patients with 46,XY
DSD and adrenal insufficiency (Glu7Stop). In vitro, SF-1 mutations affect not
only steroidogenesis but also transcription of BDNF which is involved in energy
balance. However, in contrast to mice, consequences on weight were not found in
humans with SF-1 mutations.
PMID- 25122492
TI - A review of the Fukushima nuclear reactor accident: radiation effects on the
thyroid and strategies for prevention.
AB - PURPOSE OF REVIEW: This is a summary of the nuclear accident at the Tokyo
Electric Power Company Fukushima Daiichi Nuclear Power Stations (FDNPS) on 11
March 2011 to be used as a review of the radiation effects to the thyroid and
strategies of prevention. RECENT FINDINGS: The amount of radioiodine released to
the environment following the Fukushima accident was 120 Peta Becquerel, which is
approximately one-tenth of that in the Chernobyl accident. Residents near the
FDNPS were evacuated within a few days and foodstuffs were controlled within 1 or
2 weeks. Therefore, thyroid radiation doses were less than 100 mSv (intervention
levels for stable iodine administration) in the majority of children, including
less than 1 year olds, living in the evacuation areas. Because the incidence of
childhood thyroid cancer increased in those residing near the site following the
Chernobyl accident, thyroid screening of all children (0-18 years old) in the
Fukushima Prefecture was started. To date, screening of more than 280 000
children has resulted in the diagnosis of thyroid cancer in 90 children
(approximate incidence, 313 per million). Thus, although the dose of radiation
was much lower, the incidence of thyroid cancer appears to be much higher than
that following the Chernobyl accident. SUMMARY: A comparison of the thyroidal
consequences following the Fukushima and Chernobyl nuclear reactor accidents is
discussed. We also summarize the recent increased incidence in thyroid cancer in
the Fukushima area following the accident in relation to increased thyroid
ultrasound screening and the use of advanced ultrasound techniques. VIDEO
ABSTRACT: http://links.lww.com/COE/A8.
PMID- 25122491
TI - Psychiatric and cognitive manifestations of hypothyroidism.
AB - PURPOSE OF REVIEW: Overt hypothyroidism has major effects on neuropsychiatric
function, but patients with mild hypothyroidism may attribute unrelated
neuropsychiatric symptoms to their thyroid condition. This review will summarize
data on neuropsychiatric effects of hypothyroidism, and provide guidelines
regarding the relationship between hypothyroidism and neuropsychiatric issues,
and treatment indications. RECENT FINDINGS: Clinical investigations and
functional imaging studies confirm that overt hypothyroidism is associated with
affective and cognitive decrements, largely reversible with treatment. In
contrast, subclinical hypothyroidism is not associated with major
neuropsychiatric deficits, although studies utilizing sensitive measures show
small deficits in memory and executive function. Neuropsychiatric complaints are
more common when patients are aware of their thyroid disease, regardless of their
thyroid function at the time of testing. SUMMARY: Neuropsychiatric dysfunction is
common in overt hypothyroidism and will improve (perhaps not completely resolve)
with therapy. Deficits related to thyroid dysfunction are usually mild in
subclinical hypothyroidism, and realistic expectations need to be set regarding
symptom reversibility with treatment. Patients with mild hypothyroidism and
significant distress related to neuropsychiatric symptoms, most likely, have
independent diagnoses that should be evaluated separately.
PMID- 25122495
TI - MODMatcher: multi-omics data matcher for integrative genomic analysis.
AB - Errors in sample annotation or labeling often occur in large-scale genetic or
genomic studies and are difficult to avoid completely during data generation and
management. For integrative genomic studies, it is critical to identify and
correct these errors. Different types of genetic and genomic data are inter
connected by cis-regulations. On that basis, we developed a computational
approach, Multi-Omics Data Matcher (MODMatcher), to identify and correct sample
labeling errors in multiple types of molecular data, which can be used in further
integrative analysis. Our results indicate that inspection of sample annotation
and labeling error is an indispensable data quality assurance step. Applied to a
large lung genomic study, MODMatcher increased statistically significant genetic
associations and genomic correlations by more than two-fold. In a simulation
study, MODMatcher provided more robust results by using three types of omics data
than two types of omics data. We further demonstrate that MODMatcher can be
broadly applied to large genomic data sets containing multiple types of omics
data, such as The Cancer Genome Atlas (TCGA) data sets.
PMID- 25122493
TI - How sensitive (second-generation) thyroglobulin measurement is changing paradigms
for monitoring patients with differentiated thyroid cancer, in the absence or
presence of thyroglobulin autoantibodies.
AB - PURPOSE OF REVIEW: To discuss new insights regarding how sensitive (second
generation) thyroglobulin immunometric assays (TgIMAs), (functional sensitivities
<=0.10 MUg/L) necessitate different approaches for postoperative thyroglobulin
monitoring of patients with differentiated thyroid cancer (DTC), depending on the
presence of thyroglobulin autoantibodies (TgAbs). RECENT FINDINGS: Reliable low
range serum thyroglobulin measurement has both enhanced clinical utility and
economic advantages, provided TgAb is absent (~75% DTC patients). Basal
[nonthyroid-stimulating hormone (TSH) stimulated] TgIMA measurement obviates the
need for recombinant human TSH stimulation because basal TgIMA below 0.20 MUg/L
has comparable negative predictive value (>95%) to recombinant human TSH
stimulated thyroglobulin values below the cutoff of 2 MUg/L. Now that radioiodine
remnant ablation is no longer considered necessary to treat low-risk DTC, the
trend and doubling time of low basal thyroglobulin values arising from
postsurgical thyroid remnants have recognized prognostic significance. The major
limitation of TgIMA testing is interference by TgAb (~25% DTC patients), causing
TgIMA underestimation that can mask disease. When TgAb is present, the trend in
TgAb concentrations (measured by the same method) can serve as the primary
(surrogate) tumor-marker and be augmented by thyroglobulin measured by a TgAb
resistant class of method (radioimmunoassay or liquid chromatography-tandem mass
spectrometry). SUMMARY: The growing use of TgIMA measurement is changing
paradigms for postoperative DTC monitoring. When TgAb is absent, it is optimal to
monitor the basal TgIMA trend and doubling time (using the same method) in
preference to recombinant human TSH-stimulated thyroglobulin testing. When TgAb
is present, interference renders TgIMA testing unreliable and the trend in serum
TgAb concentrations per se (same method) can serve as a (surrogate) tumor-marker.
PMID- 25122496
TI - Tyrosine 129 of the murine gammaherpesvirus M2 protein is critical for M2
function in vivo.
AB - A common strategy shared by all known gammaherpesviruses is their ability to
establish a latent infection in lymphocytes--predominantly in B cells. In
immunocompromised patients, such as transplant recipients or AIDS patients,
gammaherpesvirus infections can lead to the development of lymphoproliferative
disease and lymphoid malignancies. The human gamma-herpesviruses, EBV and KSHV,
encode proteins that are capable of modulating the host immune signaling
machinery, thereby subverting host immune responses. Murine gamma-herpesvirus 68
(MHV68) infection of laboratory strains of mice has proven to be useful small
animal model that shares important pathogenic strategies with the human gamma
herpesviruses. The MHV68 M2 protein is known to manipulate B cell signaling and,
dependent on route and dose of virus inoculation, plays a role in both the
establishment of latency and virus reactivation. M2 contains two tyrosines that
are targets for phosphorylation, and have been shown to interact with the B cell
signaling machinery. Here we describe in vitro and in vivo studies of M2 mutants
which reveals that while both tyrosines Y120 and Y129 are required for M2
induction of IL-10 expression from primary murine B cells in vitro, only Y129 is
critical for reactivation from latency and plasma cell differentiation in vivo.
PMID- 25122497
TI - Controlling asthma by training of Capnometry-Assisted Hypoventilation (CATCH) vs
slow breathing: a randomized controlled trial.
AB - BACKGROUND: Hyperventilation has been associated with adverse effects on lung
function, symptoms, and well-being in asthma. We examined whether raising end
tidal CO2 levels (ie, Pco2) compared with slow breathing is associated with
improvements in asthma control, including peak flow variability. METHODS: One
hundred twenty patients with asthma were randomly assigned to capnometry-assisted
respiratory training (CART) for raising Pco2 or slow breathing and awareness
training (SLOW) for slowing respiratory rate. Patients received five weekly
sessions and completed bid homework exercises over 4 weeks. Blinded assessments
at baseline, posttreatment, 1- and 6-month follow-up of asthma control, Pco2, and
diurnal peak flow variability were primary outcome measures. Additionally, we
measured pulmonary function (spirometry, forced oscillation, exhaled nitric
oxide, and methacholine challenge), symptoms, quality of life, and bronchodilator
use. Because the control group received active treatment, we expected
improvements in asthma control in both groups but more pronounced benefits from
CART. RESULTS: Improvements were seen in 17 of 21 clinical indexes (81.0%) in
both interventions, including the primary outcome variables asthma control (d =
0.81), peak flow variability (d = 0.54), quality of life, bronchodilator use,
lung function, and airway hyperreactivity. Most improvements were sustained
across the 6-month follow-up. Compared with slow breathing, CART showed greater
increases in Pco2 (d = 1.45 vs 0.64 for CART vs SLOW, respectively) and greater
reductions in respiratory impedance during treatment, less distress during
methacholine challenge, and greater reduction in asthma symptoms at follow-up (P
< .05). CONCLUSIONS: Brief interventions aimed at raising Pco2 or slowing
respiratory rate provide significant, sustained, and clinically meaningful
improvements in asthma control. Raising Pco2 was associated with greater benefits
in aspects of lung function and long-term symptoms. TRIAL REGISTRY:
ClinicalTrials.gov; No.: NCT00975273; URL: www.clinicaltrials.gov.
PMID- 25122498
TI - Bursts and heavy tails in temporal and sequential dynamics of foraging decisions.
AB - A fundamental understanding of behavior requires predicting when and what an
individual will choose. However, the actual temporal and sequential dynamics of
successive choices made among multiple alternatives remain unclear. In the
current study, we tested the hypothesis that there is a general bursting property
in both the timing and sequential patterns of foraging decisions. We conducted a
foraging experiment in which rats chose among four different foods over a
continuous two-week time period. Regarding when choices were made, we found
bursts of rapidly occurring actions, separated by time-varying inactive periods,
partially based on a circadian rhythm. Regarding what was chosen, we found
sequential dynamics in affective choices characterized by two key features: (a) a
highly biased choice distribution; and (b) preferential attachment, in which the
animals were more likely to choose what they had previously chosen. To capture
the temporal dynamics, we propose a dual-state model consisting of active and
inactive states. We also introduce a satiation-attainment process for bursty
activity, and a non-homogeneous Poisson process for longer inactivity between
bursts. For the sequential dynamics, we propose a dual-control model consisting
of goal-directed and habit systems, based on outcome valuation and choice
history, respectively. This study provides insights into how the bursty nature of
behavior emerges from the interaction of different underlying systems, leading to
heavy tails in the distribution of behavior over time and choices.
PMID- 25122500
TI - Plasminogen activator inhibitor-1 in aging.
AB - Plasminogen activator inhibitor-1 (PAI-1), a principal inhibitor of fibrinolysis,
is induced in thrombotic, fibrotic, and cardiovascular diseases, which in turn
primarily afflict the older population. This induction of PAI-1 may play an
important role in the pathology of these diseases as PAI-1 can regulate the
dissolution of fibrin and also inhibit the degradation of the extracellular
matrix by reducing plasmin generation. PAI-1 expression is elevated in aged
individuals and is significantly upregulated in a variety of pathologies
associated with the process of aging, including myocardial and cerebral
infarction, vascular (athero) sclerosis, cardiac and lung fibrosis, metabolic
syndromes (e.g., hypertension, hyperlipidemia, and insulin resistance), cancer,
and inflammatory/stress responses. Thus, PAI-1 may play a critical role in the
development of aging-associated pathological changes. In addition, PAI-1 is
recognized as a marker of senescence and a key member of a group of proteins
collectively known as the senescence-messaging secretome. In this review, we
highlight the role of PAI-1 in the pathophysiology of aging and aging-associated
disorders.
PMID- 25122499
TI - Thermostability of in vitro evolved Bacillus subtilis lipase A: a network and
dynamics perspective.
AB - Proteins in thermophilic organisms remain stable and function optimally at high
temperatures. Owing to their important applicability in many industrial
processes, such thermostable proteins have been studied extensively, and several
structural factors attributed to their enhanced stability. How these factors
render the emergent property of thermostability to proteins, even in situations
where no significant changes occur in their three-dimensional structures in
comparison to their mesophilic counter-parts, has remained an intriguing
question. In this study we treat Lipase A from Bacillus subtilis and its six
thermostable mutants in a unified manner and address the problem with a combined
complex network-based analysis and molecular dynamic studies to find commonality
in their properties. The Protein Contact Networks (PCN) of the wild-type and six
mutant Lipase A structures developed at a mesoscopic scale were analyzed at
global network and local node (residue) level using network parameters and
community structure analysis. The comparative PCN analysis of all proteins
pointed towards important role of specific residues in the enhanced
thermostability. Network analysis results were corroborated with finer-scale
molecular dynamics simulations at both room and high temperatures. Our results
show that this combined approach at two scales can uncover small but important
changes in the local conformations that add up to stabilize the protein structure
in thermostable mutants, even when overall conformation differences among them
are negligible. Our analysis not only supports the experimentally determined
stabilizing factors, but also unveils the important role of contacts, distributed
throughout the protein, that lead to thermostability. We propose that this
combined mesoscopic-network and fine-grained molecular dynamics approach is a
convenient and useful scheme not only to study allosteric changes leading to
protein stability in the face of negligible over-all conformational changes due
to mutations, but also in other molecular networks where change in function does
not accompany significant change in the network structure.
PMID- 25122502
TI - Quick and label-free detection for Coumaphos by using surface plasmon resonance
biochip.
AB - Coumaphos is a common organophosphorus pesticide used in agricultural products.
It is harmful to human health and has a strictly stipulated maximum residue limit
(MRL) on fruits and vegetables. Currently existing methods for detection are
complex in execution, require expensive tools and are time consuming and labor
intensive. The surface plasmon resonance method has been widely used in
biomedicine and many other fields. This study discusses a detection method based
on surface plasmon resonance in organophosphorus pesticide residues. As an
alternative solution, this study proposes a method to detect Coumaphos. The
method, which is based on surface plasmon resonance (SPR) and immune reaction,
belongs to the suppression method. A group of samples of Coumaphos was detected
by this method. The concentrations of Coumaphos in the samples were 0 ug/L, 50
ug/L, 100 ug/L, 300 ug/L, 500 ug/L, 1000 ug/L, 3000 ug/L and 5000 ug/L,
respectively. Through detecting a group of samples, the process of kinetic
reactions was analyzed and the corresponding standard curve was obtained. The
sensibility is less than 25 ug/L, conforming to the standard of the MRL of
Coumaphos stipulated by China. This method is label-free, using an unpurified
single antibody only and can continuously test at least 80 groups of samples
continuously. It has high sensitivity and specificity. The required equipments
are simple, environmental friendly and easy to control. So this method is
promised for a large number of samples quick detection on spot and for
application prospects.
PMID- 25122501
TI - Dissemination of Orientia tsutsugamushi and inflammatory responses in a murine
model of scrub typhus.
AB - Central aspects in the pathogenesis of scrub typhus, an infection caused by
Orientia (O.) tsutsugamushi, have remained obscure. Its organ and cellular
tropism are poorly understood. The purpose of this study was to analyze the
kinetics of bacterial dissemination and associated inflammatory responses in
infected tissues in an experimental scrub typhus mouse model, following infection
with the human pathogenic strain Karp. We provide a thorough analysis of O.
tsutsugamushi infection in inbred Balb/c mice using footpad inoculation, which is
close to the natural way of infection. By a novel, highly sensitive qPCR
targeting the multi copy traD genes, we quantitatively monitored the spread of O.
tsutsugamushi Karp from the skin inoculation site via the regional lymph node to
the internal target organs. The highest bacterial loads were measured in the
lung. Using confocal imaging, we also detected O. tsutsugamushi at the single
cell level in the lung and found a predominant macrophage rather than endothelial
localization. Immunohistochemical analysis of infiltrates in lung and brain
revealed differently composed lesions with specific localizations: iNOS
expressing macrophages were frequent in infiltrative parenchymal noduli, but
uncommon in perivascular lesions within these organs. Quantitative analysis of
the macrophage response by immunohistochemistry in liver, heart, lung and brain
demonstrated an early onset of macrophage activation in the liver. Serum levels
of interferon (IFN)-gamma were increased during the acute infection, and we
showed that IFN-gamma contributed to iNOS-dependent bacterial growth control. Our
data show that upon inoculation to the skin, O. tsutsugamushi spreads
systemically to a large number of organs and gives rise to organ-specific
inflammation patterns. The findings suggest an essential role for the lung in the
pathogenesis of scrub typhus. The model will allow detailed studies on host
pathogen interaction and provide further insight into the pathogenesis of O.
tsutsugamushi infection.
PMID- 25122503
TI - Nicotine intake from electronic cigarettes on initial use and after 4 weeks of
regular use.
AB - INTRODUCTION: Electronic cigarettes (EC) have the potential to generate a
substantial public health benefit if there is a switch from smoking to EC use on
a population scale. The nicotine delivery from EC is likely to play a major role
in their attractiveness to smokers. We assessed nicotine delivery from a first
generation EC and the effect of experience with its use on nicotine intake.
METHODS: Six smokers provided pharmacokinetic (PK) data after their first use of
EC and again following 4 weeks of use. RESULTS: The peak nicotine levels were
achieved within 5 min of starting the EC use, which suggests that EC may provide
nicotine via pulmonary absorption. There were large individual differences in
nicotine intake. Compared with the PK profile when using EC for the first time, 4
weeks of practice generated a 24% increase in the peak plasma concentrations
(from 4.6 to 5.7 ng/ml; nonsignificant) and a 79% increase in overall nicotine
intake (AUC(0 -> inf) increased from 115 to 206 ng*min/ml; p < .05). CONCLUSIONS:
First-generation EC provide faster nicotine absorption than nicotine replacement
products, but to compete successfully with conventional cigarettes, EC may need
to provide higher doses of nicotine. Nicotine intake from EC can increase with
practice, but further studies are needed to confirm this effect.
PMID- 25122504
TI - A maladaptive role for EP4 receptors in mouse mesangial cells.
AB - Roles of the prostaglandin E2 E-prostanoid 4 receptor (EP4) on extracellular
matrix (ECM) accumulation induced by TGF-beta1 in mouse glomerular mesangial
cells (GMCs) remain unknown. Previously, we have identified that TGF-beta1
stimulates the expression of FN and Col I in mouse GMCs. Here we asked whether
stimulation of EP4 receptors would exacerbate renal fibrosis associated with
enhanced glomerular ECM accumulation. We generated EP4(Flox/Flox) and EP4(+/-)
mice, cultured primary WT, EP4(Flox/Flox) and EP4(+/-) GMCs, AD-EP4 transfected
WT GMCs (EP4 overexpression) and AD-Cre transfected EP4(Flox/Flox) GMCs (EP4
deleted). We found that TGF-beta1-induced cAMP and PGE2 synthesis decreased in
EP4 deleted GMCs and increased in EP4 overexpressed GMCs. Elevated EP4 expression
in GMCs augmented the coupling of TGF-beta1 to FN, Col I expression and COX2/PGE2
signaling, while TGF-beta1 induced FN, Col I expression and COX2/PGE2 signaling
were down-regulated in EP4 deficiency GMCs. 8 weeks after 5/6 nephrectomy (Nx),
WT and EP4(+/-) mice exhibited markedly increased accumulation of ECM compared
with sham-operated controls. Albuminuria, blood urea nitrogen and creatinine (BUN
and Cr) concentrations were significantly increased in WT mice as compared to
those of EP4(+/-) mice. Urine osmotic pressure was dramatically decreased after
5/6 Nx surgery in WT mice as compared to EP4(+/-) mice. The pathological changes
in kidney of EP4(+/-) mice was markedly alleviated compared with WT mice.
Immunohistochemical analysis showed significant reductions of Col I and FN in the
kidney of EP4(+/-) mice compared with WT mice. Collectively, this investigation
established EP4 as a potent mediator of the pro-TGF-beta1 activities elicited by
COX2/PGE2 in mice GMCs. Our findings suggested that prostaglandin E2, acting via
EP4 receptors contributed to accumulation of ECM in GMCs and promoted renal
fibrosis.
PMID- 25122506
TI - Minimally invasive intervention for infected necrosis in acute pancreatitis.
AB - Infected necrosis is the main indication for invasive intervention in acute
necrotizing pancreatitis. The 2013 IAP/APA guidelines state that percutaneous
catheter drainage should be the first step in the treatment of infected necrosis.
In 50-65% of patients, additional necrosectomy is required after catheter
drainage, which was traditionally done by open necrosectomy. Driven by the
perceived lower complication rate, there is an increasing trend toward minimally
invasive percutaneous and endoscopic transluminal necrosectomy. The authors
present an overview of current minimally invasive treatment options for
necrotizing pancreatitis and review recent developments in clinical studies.
PMID- 25122505
TI - Antiplatelet effect of catechol is related to inhibition of cyclooxygenase,
reactive oxygen species, ERK/p38 signaling and thromboxane A2 production.
AB - Catechol (benzenediol) is present in plant-derived products, such as vegetables,
fruits, coffee, tea, wine, areca nut and cigarette smoke. Because platelet
dysfunction is a risk factor of cardiovascular diseases, including stroke,
atherosclerosis and myocardial infarction, the purpose of this study was to
evaluate the anti-platelet and anti-inflammatory effect of catechol and its
mechanisms. The effects of catechol on cyclooxygenase (COX) activity, arachidonic
acid (AA)-induced aggregation, thromboxane B2 (TXB2) production, lactate
dehydrogenase (LDH) release, reactive oxygen species (ROS) production and
extracellular signal-regulated kinase (ERK)/p38 phosphorylation were determined
in rabbit platelets. In addition, its effect on IL-1beta-induced prostaglandin E2
(PGE2) production by fibroblasts was determined. The ex vivo effect of catechol
on platelet aggregation was also measured. Catechol (5-25 uM) suppressed AA
induced platelet aggregation and inhibited TXB2 production at concentrations of
0.5-5 uM; however, it showed little cytotoxicity and did not alter U46619-induced
platelet aggregation. Catechol (10-50 uM) suppressed COX-1 activity by 29-44% and
COX-2 activity by 29-50%. It also inhibited IL-1beta-induced PGE2 production, but
not COX-2 expression of fibroblasts. Moreover, catechol (1-10 uM) attenuated AA
induced ROS production in platelets and phorbol myristate acetate (PMA)-induced
ROS production in human polymorphonuclear leukocytes. Exposure of platelets to
catechol decreased AA-induced ERK and p38 phosphorylation. Finally, intravenous
administration of catechol (2.5-5 umole/mouse) attenuated ex vivo AA-induced
platelet aggregation. These results suggest that catechol exhibited anti-platelet
and anti-inflammatory effects, which were mediated by inhibition of COX, ROS and
TXA2 production as well as ERK/p38 phosphorylation. The anti-platelet effect of
catechol was confirmed by ex vivo analysis. Exposure to catechol may affect
platelet function and thus cardiovascular health.
PMID- 25122507
TI - Domain organization, catalysis and regulation of eukaryotic cystathionine beta
synthases.
AB - Cystathionine beta-synthase (CBS) is a key regulator of sulfur amino acid
metabolism diverting homocysteine, a toxic intermediate of the methionine cycle,
via the transsulfuration pathway to the biosynthesis of cysteine. Although the
pathway itself is well conserved among eukaryotes, properties of eukaryotic CBS
enzymes vary greatly. Here we present a side-by-side biochemical and biophysical
comparison of human (hCBS), fruit fly (dCBS) and yeast (yCBS) enzymes.
Preparation and characterization of the full-length and truncated enzymes,
lacking the regulatory domains, suggested that eukaryotic CBS exists in one of at
least two significantly different conformations impacting the enzyme's catalytic
activity, oligomeric status and regulation. Truncation of hCBS and yCBS, but not
dCBS, resulted in enzyme activation and formation of dimers compared to native
tetramers. The dCBS and yCBS are not regulated by the allosteric activator of
hCBS, S-adenosylmethionine (AdoMet); however, they have significantly higher
specific activities in the canonical as well as alternative reactions compared to
hCBS. Unlike yCBS, the heme-containing dCBS and hCBS showed increased thermal
stability and retention of the enzyme's catalytic activity. The mass-spectrometry
analysis and isothermal titration calorimetry showed clear presence and binding
of AdoMet to yCBS and hCBS, but not dCBS. However, the role of AdoMet binding to
yCBS remains unclear, unlike its role in hCBS. This study provides valuable
information for understanding the complexity of the domain organization,
catalytic specificity and regulation among eukaryotic CBS enzymes.
PMID- 25122510
TI - The palliative performance scale applied in high-care residential hospice: a
retrospective study.
AB - BACKGROUND: The Palliative Performance Scale (PPS) is a tool that is widely used
to predict end of life. In Ontario, Canada, the PPS is used to mark the terminal
phase of life and eligibility for terminal care. OBJECTIVE: The aim of this
retrospective study was to confirm that a PPS level of 40% can be used as a
marker for the terminal phase of life. METHOD: PPS levels from 78 patients were
calculated based on the intake reports made at admission to an inpatient hospice.
RESULTS: Although 77 patients passed away within a period of 3 months, PPS levels
at admission varied from 10% to 70%. Fifty-six percent of all patients had a PPS
level of 40% or less. Regarding survival, three significant PPS profiles,
consisting of two or more PPS levels could be distinguished.
PMID- 25122508
TI - Saccadic eye movements in depressed elderly patients.
AB - The primary aim of this study was to characterize oculomotor performances in
elderly depressed patients. The second aim was to investigate whether cognitive
inhibition measured by the antisaccade task was associated with a psychomotor
retardation or rather with a more specific cognitive-motor inhibition deficit.
Twenty patients with a major depressive disorder and forty-seven healthy subjects
performed two eye movement tasks. Saccadic reaction time and error rates were
analyzed in the prosaccade task to obtain basic parameters of eye movements.
Saccade latency, error rates and correction rates were evaluated in the
antisaccade task to investigate inhibition capacities. Performances were impaired
in patients, who exhibited a higher reaction time and error rates compared to
controls. The higher time cost of inhibition suggested that the reaction time was
not related to global psychomotor retardation alone. The higher time cost of
inhibition could be explained by a specific alteration of inhibition processes
evaluated by the antisaccade task. These changes were associated with the
severity of depression. These findings provide a new perspective on cognitive
inhibition in elderly depressed patients and could have important clinical
implications for our understanding of critical behaviors involving deficits in
inhibitory processes in the elderly.
PMID- 25122511
TI - Poisson indicator and Fano factor for probing dynamic disorder in single-molecule
enzyme inhibition kinetics.
AB - We consider a generic stochastic model to describe the kinetics of single
molecule enzyme inhibition reactions in which the turnover events correspond to
conversion of substrate into a product by a single enzyme molecule in the
presence of an inhibitor. We observe that slow fluctuations between the active
and inhibited state of the enzyme or the enzyme substrate complex can induce
dynamic disorder, which is manifested in the measurement of the Poisson indicator
and the Fano factor as functions of substrate concentrations for different
inhibition reactions. For a single enzyme molecule inhibited by the product, we
derive a single-molecule Michaelis-Menten equation for the reaction rate, which
shows a dependence on the substrate concentration similar to the ensemble
enzymatic catalysis rate as obtained from bulk experimental results. The
measurement of Fano factor is shown to be able to discriminate reactions
following different inhibition mechanisms and also extract kinetic rates.
PMID- 25122509
TI - Effects of baseline problematic alcohol and drug use on internet-based cognitive
behavioral therapy outcomes for depression, panic disorder and social anxiety
disorder.
AB - PURPOSE: Patients' problematic substance use prevalence and effects were explored
in relation to internet-based cognitive behavioral therapy (ICBT) outcomes for
depression, panic disorder and social anxiety disorder. METHODS: At baseline and
treatment conclusion, 1601 ICBT patients were assessed with self-rated measures
for alcohol and drug use (AUDIT/DUDIT), depressive symptoms (MADRS-S), panic
disorder symptoms (PDSS-SR) and social anxiety symptoms (LSAS-SR). RESULTS:
Problematic substance use (AUDIT >= 8 for men, >= 6 for women; DUDIT >= 1)
occurred among 32.4% of the patients; 24.1% only alcohol, 4.6% only drugs, and
3.7% combined alcohol and drug use. Hazardous alcohol use and probable alcohol
dependence negatively affected panic disorder outcomes, and hazardous drug use
led to worse social anxiety outcomes. Depression outcomes were not affected by
substance use. Treatment adherence was negatively affected by problematic drug
use among men and 25-34 year olds; combined substance use negatively affected
adherence for women and 35-64 year olds. CONCLUSION: Problematic substance use
does not preclude ICBT treatment but can worsen outcomes, particularly
problematic alcohol use for panic disorder patients and hazardous drug use for
social anxiety patients. ICBT clinicians should exercise particular caution when
treating men and younger patients with problematic drug use, and women or older
patients with combined substance use.
PMID- 25122512
TI - Ultrasound current source density imaging of the cardiac activation wave using a
clinical cardiac catheter.
AB - Ultrasound current source density imaging (UCSDI), based on the acoustoelectric
(AE) effect, is a noninvasive method for mapping electrical current in 4-D (space
+ time). This technique potentially overcomes limitations with conventional
electrical mapping procedures typically used during treatment of sustained
arrhythmias. However, the weak AE signal associated with the electrocardiogram is
a major challenge for advancing this technology. In this study, we examined the
effects of the electrode configuration and ultrasound frequency on the magnitude
of the AE signal and quality of UCSDI using a rabbit Langendorff heart
preparation. The AE signal was much stronger at 0.5 MHz (2.99 MUV/MPa) than 1.0
MHz (0.42 MUV/MPa). Also, a clinical lasso catheter placed on the epicardium
exhibited excellent sensitivity without penetrating the tissue. We also present,
for the first time, 3-D cardiac activation maps of the live rabbit heart using
only one pair of recording electrodes. Activation maps were used to calculate the
cardiac conduction velocity for atrial (1.31 m/s) and apical (0.67 m/s) pacing.
This study demonstrated that UCSDI is potentially capable of real-time 3-D
cardiac activation wave mapping, which would greatly facilitate ablation
procedures for treatment of arrhythmias.
PMID- 25122514
TI - We are both doctors: an Israeli doctor writes to a Palestinian colleague.
PMID- 25122513
TI - Cationic charged helical glycopolypeptide using ring opening polymerization of 6
deoxy-6-azido-glyco-N-carboxyanhydride.
AB - Glycopolypeptides with a defined secondary structure are of significance in
understanding biological phenomena. Synthetic glycopolypeptides, or polypeptides
featuring pendant carbohydrate moieties, have been of particular interest in the
field of tissue engineering and drug delivery. In this work, we have synthesized
charged water-soluble glycopolypeptides that adopt a helical conformation in
water. This was carried out by the synthesis of a glyco-N-carboxyanhydride (glyco
NCA) containing an azide group at the sixth position of the carbohydrate ring.
Subsequently, the NCA was polymerized to obtain azide-containing
glycopolypeptides having good control over molecular weight and polydispersity
index (PDI) in high yields. We were also able to control the incorporation of the
azide group by synthesizing random co-glycopolypeptide containing 6-deoxy-6-azido
and regular 6-OAc functionalized glucose. This azide functionality allows for the
easy attachment of a bioactive group, which could potentially enhance the
biological activity of the glycopolypeptide. We were able to obtain water-soluble
charged glycopolypeptides by both reducing the azide groups into amines and using
CuAAC with propargylamine. These charged glycopolypeptides were shown to have a
helical conformation in water. Preliminary studies showed that these charged
glycopolypeptides showed good biocompatibility and were efficiently taken up by
HepG2 cells.
PMID- 25122515
TI - Steered quantum dynamics for energy minimization.
AB - We introduce a quantum optimal control algorithm for energy minimization that
combines the diffeomorphic modulation under observable response preserving
homotopy (D-MORPH) gradient and the Broyden Fletcher Goldfarb Shanno (BFGS)
iterative scheme for nonlinear optimization. An extended set of controls defining
the time-dependent mass, dipole moment, and external perturbational field are
optimized to find an effective Hamiltonian that steers the dynamics of the system
into the global minimum without getting trapped into local minima. The algorithm
is illustrated as applied to energy minimization on rugged surfaces and golf
potentials comparable to those previously explored for testing quantum annealing
methodologies.
PMID- 25122517
TI - Characteristics of persons with corrective lenses, United States -1971.
AB - This report from the Health Interview Survey presents data on the use of
corrective lenses for persons 3 years of age and over. Estimates are derived from
a survey during 1971 of the civilian, noninstitutionalized population of the
United States. Corrective lenses include eyeglasses and contact lenses. The term
"corrective Ienses" is limited to visual aids worn to correct or improve vision
and therefore excludes sunglasses worn only to filter light, safety glasses worn
only for protection of the eyes, hand magnifying glasses, and other such devices.
However, if the safety glasses are worn also for correction or improvement of
vision, they are considered corrective lenses, as are prescription glasses. This
report analyzes use of corrective Ienses by various demographic characteristics.
An earlier report from the Health Interview Survey presented data on corrective
lenses based on the July 1965-June 1966 survey. It contained information on age
at which persons first obtained corrective lenses, type of prescription, usage,
and the source of the optical examination if the individual was examined during
the 2-year period prior to interview ("Characteristics of Persons with Corrective
Lenses: United States, July 1965-June 1966," Vital and Health Statistics, Series
10, Number 53). A later section of the present report compares demographic
differences in the proportion of the population with corrective lenses for the
two time periods.
PMID- 25122516
TI - Infrageneric phylogeny and temporal divergence of Sorghum (Andropogoneae,
Poaceae) based on low-copy nuclear and plastid sequences.
AB - The infrageneric phylogeny and temporal divergence of Sorghum were explored in
the present study. Sequence data of two low-copy nuclear (LCN) genes,
phosphoenolpyruvate carboxylase 4 (Pepc4) and granule-bound starch synthase I
(GBSSI), from 79 accessions of Sorghum plus Cleistachne sorghoides together with
those from outgroups were used for maximum likelihood (ML) and Bayesian inference
(BI) analyses. Bayesian dating based on three plastid DNA markers (ndhA intron,
rpl32-trnL, and rps16 intron) was used to estimate the ages of major
diversification events in Sorghum. The monophyly of Sorghum plus Cleistachne
sorghoides (with the latter nested within Sorghum) was strongly supported by the
Pepc4 data using BI analysis, and the monophyly of Sorghum was strongly supported
by GBSSI data using both ML and BI analyses. Sorghum was divided into three
clades in the Pepc4, GBSSI, and plastid phylograms: the subg. Sorghum lineage;
the subg. Parasorghum and Stiposorghum lineage; and the subg. Chaetosorghum and
Heterosorghum lineage. Two LCN homoeologous loci of Cleistachne sorghoides were
first discovered in the same accession. Sorghum arundinaceum, S. bicolor, S. x
drummondii, S. propinquum, and S. virgatum were closely related to S. x almum in
the Pepc4, GBSSI, and plastid phylograms, suggesting that they may be potential
genome donors to S. almum. Multiple LCN and plastid allelic variants have been
identified in S. halepense of subg. Sorghum. The crown ages of Sorghum plus
Cleistachne sorghoides and subg. Sorghum are estimated to be 12.7 million years
ago (Mya) and 8.6 Mya, respectively. Molecular results support the recognition of
three distinct subgenera in Sorghum: subg. Chaetosorghum with two sections, each
with a single species, subg. Parasorghum with 17 species, and subg. Sorghum with
nine species and we also provide a new nomenclatural combination, Sorghum
sorghoides.
PMID- 25122518
TI - Synthesis of neplanocin A and its 3'-epimer via an intramolecular Baylis-Hillman
reaction.
AB - The key cyclopentenyl intermediate 11b was synthesized in 4 steps from d-ribose
in 41% overall yield via an efficient intramolecular Baylis-Hillman reaction.
This novel key intermediate can be modified easily and transformed to neplanocin
A (1a) and its 3'-epimer (1b).
PMID- 25122519
TI - Breast-cancer patients' participation behavior and coping during presurgical
consultations: a pilot study.
AB - In the context of breast-cancer care, there is extremely little research on the
association between observed (i.e., taped and coded) communication behaviors and
patients' health outcomes, especially those other than satisfaction. In the
context of presurgical consultations between female breast cancer patients and a
surgeon, the aim of this exploratory study was to test the association between
communication-based participation behaviors and pre-post consultation changes in
aspects of patients' mental adjustment to cancer (i.e., coping). Participants
included 51 women newly diagnosed with breast cancer and a surgical oncologist
from a National Cancer Institute (NCI)-designated cancer center in the
northeastern United States. Outcomes were changes in patients' fighting spirit,
helplessness/hopelessness, anxious preoccupation, cognitive avoidance, and
fatalism (measured immediately before and after consultations via survey), and
the main predictors were three communication-based participation behaviors coded
from videotapes of consultations: patient question asking, patient assertion of
treatment preferences, and surgeon solicitation of patient
question/concern/opinion. Patients who more frequently asserted their treatment
preferences experienced increases in their fighting spirit (p = .01) and
decreases in their anxious preoccupation (p = .02). When companions (e.g.,
sister, spouse) asked more questions, patients experienced decreases in their
anxious preoccupation (p = .05). These findings suggest that, in the present
context, there may be specific, trainable communication behaviors, such as
patients asserting their treatment preferences and companions asking questions,
that may improve patients' psychosocial health outcomes.
PMID- 25122520
TI - A mitochondria-targetable fluorescent probe for dual-channel NO imaging assisted
by intracellular cysteine and glutathione.
AB - A mitochondria-specific fluorescent probe for NO (1) was synthesized by the
direct conjugation of a pyronin dye with one of the amino groups of o
phenylenediamino (OPD). The probe could selectively detect NO over
dehydroascorbic acid (DHA), ascorbic acid (AA), and methylglyoxal (MGO) as well
as the reactive oxygen/nitrogen species (ROS/RNS) with the significant off-on
response due to the production of a red-emission triazole 2. In the presence of
cysteine/glutathione (Cys/GSH), 2 could be further transformed into a green
emission aminopyronin 4 and a red-emission thiopyronin 5, respectively. Assisted
by intracellular Cys and GSH, the probe demonstrated its potential to monitor
mitochondrial NO in a dual-channel mode.
PMID- 25122521
TI - "The Castle of Remembrance": New insights from a cognitive training programme for
autobiographical memory in Alzheimer's disease.
AB - Autobiographical memory deficits are prominent from the early stages of
Alzheimer's disease (AD) and result in a loss of personal identity. Nevertheless,
standardised methods of autobiographical memory stimulation for the
neuropsychological rehabilitation of patients with AD remain underdeveloped. Our
aim was to evaluate the impact of a new cognitive training programme for
autobiographical memory (REMau) on both the episodic and semantic components of
autobiographical memory performance across lifetime periods, as well as on mood.
Pre/post evaluations were conducted on two groups of patients with early to
moderate AD, assigned to one of two different training activities: either the
REMau or a cognitive training programme focused on collective semantic memory.
Statistical comparisons showed significant improvement of episodic and semantic
autobiographical memory performance in the REMau group, which was more pronounced
for the semantic component, as well as improved mood. By contrast, deleterious
pre/post differences were observed in the other group. Most interestingly, this
study showed that the REMau programme boosted autobiographical memory from the
reminiscence bump period, which is considered crucial for the construction and
maintenance of personal identity. We discuss the theoretical and practical
implications of these results for the reduction of autobiographical memory
deficits in AD.
PMID- 25122522
TI - Preparation of microcrystals in lipidic cubic phase for serial femtosecond
crystallography.
AB - We have recently established a procedure for serial femtosecond crystallography
(SFX) in lipidic cubic phase (LCP) for protein structure determination at X-ray
free-electron lasers (XFELs). LCP-SFX uses the gel-like LCP as a matrix for
growth and delivery of membrane protein microcrystals for crystallographic data
collection. LCP is a liquid-crystalline mesophase composed of lipids and water.
It provides a membrane-mimicking environment that stabilizes membrane proteins
and supports their crystallization. Here we describe detailed procedures for the
preparation and characterization of microcrystals for LCP-SFX applications. The
advantages of LCP-SFX over traditional crystallographic methods include the
capability of collecting room-temperature high-resolution data with minimal
effects of radiation damage from sub-10-MUm crystals of membrane and soluble
proteins that are difficult to crystallize, while eliminating the need for
crystal harvesting and cryo-cooling. Compared with SFX methods for microcrystals
in solution using liquid injectors, LCP-SFX reduces protein consumption by 2-3
orders of magnitude for data collection at currently available XFELs. The whole
procedure typically takes 3-5 d, including the time required for the crystals to
grow.
PMID- 25122523
TI - Addition of exogenous alpha-synuclein preformed fibrils to primary neuronal
cultures to seed recruitment of endogenous alpha-synuclein to Lewy body and Lewy
neurite-like aggregates.
AB - This protocol describes a primary neuronal model of formation of alpha-synuclein
(alpha-syn) aggregates that recapitulate features of the Lewy bodies and Lewy
neurites found in Parkinson's disease brains and other synucleinopathies. This
model allows investigation of aggregate formation, their impact on neuron
function, and development of therapeutics. Addition of preformed fibrils (PFFs)
synthesized from recombinant alpha-syn to neurons seeds the recruitment of
endogenous alpha-syn into aggregates characterized by detergent insolubility and
hyperphosphorylation. Aggregate formation follows a lag phase of 2-3 d, followed
by formation in axons by days 4-7, spread to somatodendritic compartments by days
7-10 and neuron death ~14 d after PFF addition. Here we provide methods and
highlight the crucial steps for PFF formation, PFF addition to cultured
hippocampal neurons and confirmation of aggregate formation. Neurons derived from
various brain regions from nontransgenic and genetically engineered mice and rats
can be used, allowing interrogation of the effect of specific genes on aggregate
formation.
PMID- 25122524
TI - Similarity-based modeling in large-scale prediction of drug-drug interactions.
AB - Drug-drug interactions (DDIs) are a major cause of adverse drug effects and a
public health concern, as they increase hospital care expenses and reduce
patients' quality of life. DDI detection is, therefore, an important objective in
patient safety, one whose pursuit affects drug development and pharmacovigilance.
In this article, we describe a protocol applicable on a large scale to predict
novel DDIs based on similarity of drug interaction candidates to drugs involved
in established DDIs. The method integrates a reference standard database of known
DDIs with drug similarity information extracted from different sources, such as
2D and 3D molecular structure, interaction profile, target and side-effect
similarities. The method is interpretable in that it generates drug interaction
candidates that are traceable to pharmacological or clinical effects. We describe
a protocol with applications in patient safety and preclinical toxicity
screening. The time frame to implement this protocol is 5-7 h, with additional
time potentially necessary, depending on the complexity of the reference standard
DDI database and the similarity measures implemented.
PMID- 25122526
TI - Metal-free sp(3) C-H functionalization: a novel approach for the syntheses of
selenide ethers and thioesters from methyl arenes.
AB - A DTBP-promoted metal-free and solvent-free formation of C-Se and C-S bonds
through sp(3) C-H functionalization of methyl arenes with diselenides and
disulfides is described.
PMID- 25122527
TI - It's all in the communication.
PMID- 25122525
TI - Tracheal tissue engineering in rats.
AB - Tissue-engineered tracheal transplants have been successfully performed
clinically. However, before becoming a routine clinical procedure, further
preclinical studies are necessary to determine the underlying mechanisms of in
situ tissue regeneration. Here we describe a protocol using a tissue engineering
strategy and orthotopic transplantation of either natural decellularized donor
tracheae or artificial electrospun nanofiber scaffolds into a rat model. The
protocol includes details regarding how to assess the scaffolds' biomechanical
properties and cell viability before implantation. It is a reliable and
reproducible model that can be used to investigate the crucial aspects and
pathways of in situ tracheal tissue restoration and regeneration. The model can
be established in <6 months, and it may also provide a means to investigate cell
surface interactions, cell differentiation and stem cell fate.
PMID- 25122528
TI - Current estimates, from the health interview survey, United States-1972.
AB - National estimates of the basic health variables collected in the 1972 Health
Interview Survey of the civilian noninstitutionalized population are presented in
this report. While the detailed tables in this report contain data by age and sex
categories, later reports will present more detailed analysis of similar data by
additional selected demographic variables. The text tables present data for 1970
and 1971 as well as for 1972; however, the discussion is limited largely to
changes occurring between 1971 and 1972, since the previous report (Current
Estimates, Series 10, No. 79) compares the 1970 and 1971 data.
PMID- 25122529
TI - Use of Systematic Methods to Improve Disease Identification in Administrative
Data: The Case of Severe Sepsis.
AB - BACKGROUND: Selection of International Classification of Diseases (ICD)-based
coded information for complex conditions such as severe sepsis is a subjective
process and the results are sensitive to the codes selected. We use an innovative
data exploration method to guide ICD-based case selection for severe sepsis.
METHODS: Using the Nationwide Inpatient Sample, we applied Latent Class Analysis
(LCA) to determine if medical coders follow any uniform and sensible coding for
observations with severe sepsis. We examined whether ICD-9 codes specific to
sepsis (038.xx for septicemia, a subset of 995.9 codes representing Systemic
Inflammatory Response syndrome, and 785.52 for septic shock) could all be members
of the same latent class. RESULTS: Hospitalizations coded with sepsis-specific
codes could be assigned to a latent class of their own. This class constituted
22.8% of all potential sepsis observations. The probability of an observation
with any sepsis-specific codes being assigned to the residual class was near 0.
The chance of an observation in the residual class having a sepsis-specific code
as the principal diagnosis was close to 0. Validity of sepsis class assignment is
supported by empirical results, which indicated that in-hospital deaths in the
sepsis-specific class were around 4 times as likely as that in the residual
class. CONCLUSIONS: The conventional methods of defining severe sepsis cases in
observational data substantially misclassify sepsis cases. We suggest a
methodology that helps reliable selection of ICD codes for conditions that
require complex coding.
PMID- 25122530
TI - Persistent medication affordability problems among disabled Medicare
beneficiaries after Part D, 2006-2011.
AB - BACKGROUND: Disabled Americans who qualify for Medicare coverage typically have
multiple chronic conditions, are highly dependent on effective drug therapy, and
have limited financial resources, putting them at risk for cost-related
medication nonadherence (CRN). Since 2006, the Part D benefit has helped Medicare
beneficiaries afford medications. OBJECTIVE: To investigate recent national
trends in medication affordability among this vulnerable population, stratified
by morbidity burden. DESIGN AND SUBJECTS: We estimated annual rates of medication
affordability among nonelderly disabled participants in a nationally
representative survey (2006-2011, n=14,091 person-years) using multivariate
logistic regression analyses. MEASURE: Survey-reported CRN and spending less on
other basic needs to afford medicines. RESULTS: In the 6 years following Part D
implementation, the proportion of disabled Medicare beneficiaries reporting CRN
ranged from 31.6% to 35.6%, while the reported prevalence of spending less on
other basic needs to afford medicines ranged from 17.7% to 21.8%. Across study
years, those with multiple chronic conditions had consistently worse
affordability problems. In 2011, the prevalence of CRN was 37.3% among disabled
beneficiaries with >= 3 morbidities as compared with 28.1% among those with fewer
morbidities; for spending less on basic needs, the prevalence was 25.4% versus
15.7%, respectively. There were no statistically detectable changes in either
measure when comparing 2011 with 2007. CONCLUSIONS: Disabled Medicare
beneficiaries continue to struggle to afford prescription medications. There is
an urgent need for focused policy attention on this vulnerable population, which
has inadequate financial access to drug treatments, despite having drug coverage
under Medicare Part D.
PMID- 25122531
TI - The ecological fallacy of the role of age in chronic disease and hospital demand.
AB - OBJECTIVE: To examine the relationship between age and all-cause hospital
utilization in the years preceding and following a diagnosis in hospital of heart
failure, type 2 diabetes, or chronic obstructive pulmonary disease (COPD).
RESEARCH DESIGN: A cohort study of all patients in Western Australia who have had
a principal diagnosis of heart failure, type 2 diabetes, or COPD, upon admission
to hospital. All-cause hospital utilization 6 years preceding and 4 years
following cardinal events, that is, a disease-specific diagnosis upon hospital
admission, where such an event has not occurred in the previous 2 years, are
examined in specific age groups. RESULTS: Six years preceding a cardinal event,
all-cause emergency department (ED) presentations are similar in all age groups,
from under 55 to over 85 years of age, except in COPD where ED presentation rates
are higher in younger groups. All-cause hospital inpatient days are transiently
higher in the years preceding and following a cardinal event in older age groups,
yet return to similar levels across all age cohorts after 4 years. ED
presentations are significantly higher in the 4 years following cardinal events
in younger compared with older groups. CONCLUSIONS: Longitudinal analysis of
utilization around cardinal events overcomes the confounding effect of
differences in chronic disease rates between age groups, avoiding a source of
ecologic bias that erroneously attributes increasing utilization in individuals
with chronic disease to age. Programs designed to reduce hospital demand in
patients with chronic disease should possibly focus on younger, rather than
older, individuals.
PMID- 25122532
TI - Comb-push ultrasound shear elastography (CUSE) for evaluation of thyroid nodules:
preliminary in vivo results.
AB - In clinical practice, an overwhelming majority of biopsied thyroid nodules are
benign. Therefore, there is a need for a complementary and noninvasive imaging
tool to provide clinically relevant diagnostic information about thyroid nodules
to reduce the rate of unnecessary biopsies. The goal of this study was to
evaluate the feasibility of utilizing comb-push ultrasound shear elastography
(CUSE) to measure the mechanical properties (i.e., stiffness) of thyroid nodules
and use this information to help classify nodules as benign or malignant. CUSE is
a fast and robust 2-D shear elastography technique in which multiple laterally
distributed acoustic radiation force beams are utilized simultaneously to produce
shear waves. Unlike other shear elasticity imaging modalities, CUSE does not
suffer from limited field of view (FOV) due to shear wave attenuation and can
provide a large FOV at high frame rates. To evaluate the utility of CUSE in
thyroid imaging, a preliminary study was performed on a group of five healthy
volunteers and 10 patients with ultrasound-detected thyroid nodules prior to fine
needle aspiration biopsy. The measured shear wave speeds in normal thyroid tissue
and thyroid nodules were converted to Young's modulus (E), indicating a measure
of tissue stiffness. Our results indicate an increase in E for thyroid nodules
compared to normal thyroid tissue. This increase was significantly higher in
malignant nodules compared to benign. The Young's modulus in normal thyroid
tissue, benign and malignant nodules were found to be 23.2 +/-8.29 kPa, 91.2+/
34.8 kPa, and 173.0+/-17.1 kPa, respectively. Results of this study suggest the
utility of CUSE in differentiating between benign and malignant thyroid nodules.
PMID- 25122533
TI - Design, synthesis, and biological evaluation of stable colchicine binding site
tubulin inhibitors as potential anticancer agents.
AB - To block the metabolically labile sites of novel tubulin inhibitors targeting the
colchicine binding site based on SMART, ABI, and PAT templates, we have designed,
synthesized, and biologically tested three focused sets of new derivatives with
modifications at the carbonyl linker, the para-position in the C ring of SMART
template, and modification of A ring of the PAT template. Structure-activity
relationships of these compounds led to the identification of new benzimidazole
and imidazo[4,5-c]pyridine-fused ring templates, represented by compounds 4 and
7, respectively, which showed enhanced antitumor activity and substantially
improved the metabolic stability in liver microsomes compared to SMART. MOM group
replaced TMP C ring and generated a potent analogue 15, which showed comparable
potency to the parent SMART compound. Further modification of PAT template
yielded another potent analogue 33 with 5-indolyl substituent at A ring.
PMID- 25122534
TI - Monolithic gyroidal mesoporous mixed titanium-niobium nitrides.
AB - Mesoporous transition metal nitrides are interesting materials for energy
conversion and storage applications due to their conductivity and durability. We
present ordered mixed titanium-niobium (8:2, 1:1) nitrides with gyroidal network
structures synthesized from triblock terpolymer structure-directed mixed oxides.
The materials retain both macroscopic integrity and mesoscale ordering despite
heat treatment up to 600 degrees C, without a rigid carbon framework as a
support. Furthermore, the gyroidal lattice parameters were varied by changing
polymer molar mass. This synthesis strategy may prove useful in generating a
variety of monolithic ordered mesoporous mixed oxides and nitrides for electrode
and catalyst materials.
PMID- 25122535
TI - Bias voltage induced resistance switching effect in single-molecule magnets'
tunneling junction.
AB - An electric-pulse-induced reversible resistance change effect in a molecular
magnetic tunneling junction, consisting of a single-molecule magnet (SMM)
sandwiched in one nonmagnetic and one ferromagnetic electrode, is theoretically
investigated. By applying a time-varying bias voltage, the SMM's spin orientation
can be manipulated with large bias voltage pulses. Moreover, the different
magnetic configuration at high-resistance/low-resistance states can be 'read out'
by utilizing relative low bias voltage. This device scheme can be implemented
with current technologies (Khajetoorians et al 2013 Science 339 55) and has
potential application in molecular spintronics and high-density nonvolatile
memory devices.
PMID- 25122537
TI - Postoperative neurocognitive dysfunction in elderly patients after xenon versus
propofol anesthesia for major noncardiac surgery: a double-blinded randomized
controlled pilot study: retraction.
PMID- 25122536
TI - Evaluation of the Macular Choroidal Thickness Using Spectral Optical Coherence
Tomography in Pseudoexfoliation Glaucoma.
AB - PURPOSE: To evaluate the choroidal thickness (CT) in pseudoexfoliative (PEX)
glaucoma and age-matched healthy subjects using spectral optical coherence
tomography (SD-OCT). PATIENTS AND METHODS: In this prospective study, 32 eyes of
32 PEX glaucoma patients and 30 eyes of 30 age-matched healthy subjects were
enrolled. The CT is measured perpendicularly (from the outer edge of the
hyperreflective retinal pigment epithelium to the inner sclera) at the fovea, and
1.5 mm temporal, 3.0 mm temporal, 1.5 mm nasal, and 3.0 mm nasal to the fovea
using SD-OCT (RTVue-100). RESULTS: The groups were similar regarding the mean age
and axial length values (both, P>0.05). The CT measurements were 182.12 +/- 39.88
and 201.56 +/- 32.00 MUm at 1.5 mm nasal to the fovea (P=0.039), and 126.47 +/-
32.12 and 146.60 +/- 31.37 MUm at 3.0 mm nasal to the fovea (P=0.015) in the PEX
glaucoma and control groups, respectively. There were no significant differences
in the subfoveal and temporal CT measurements among the 2 groups (all, P>0.05).
CONCLUSIONS: The findings of this study indicate that PEX glaucoma causes
significant thinning in the nasal choroid. Thus, measuring the CT with SD-OCT may
be the way of better clarification of the relationship between PEX and
glaucomatous optic neuropathy.
PMID- 25122538
TI - Fungal natural products in research and development.
AB - To date approximately 100 000 fungal species are known although far more than one
million are expected. The variety of species and the diversity of their habitats,
some of them less exploited, allow the conclusion that fungi continue to be a
rich source of new metabolites. Besides the conventional fungal isolates, an
increasing interest in endophytic and in marine-derived fungi has been noticed.
In addition new screening strategies based on innovative chemical, biological,
and genetic approaches have led to novel fungal metabolites in recent years. The
present review focuses on new fungal natural products published from 2009 to 2013
highlighting the originality of the structures and their biological potential.
Furthermore synthetic products based on fungal metabolites as well as new
developments in the uses or the biological activity of known compounds or new
derivatives are discussed.
PMID- 25122540
TI - Nanoparticle size detection limits by single particle ICP-MS for 40 elements.
AB - The quantification and characterization of natural, engineered, and incidental
nano- to micro-size particles are beneficial to assessing a nanomaterial's
performance in manufacturing, their fate and transport in the environment, and
their potential risk to human health. Single particle inductively coupled plasma
mass spectrometry (spICP-MS) can sensitively quantify the amount and size
distribution of metallic nanoparticles suspended in aqueous matrices. To
accurately obtain the nanoparticle size distribution, it is critical to have
knowledge of the size detection limit (denoted as Dmin) using spICP-MS for a wide
range of elements (other than a few available assessed ones) that have been or
will be synthesized into engineered nanoparticles. Herein is described a method
to estimate the size detection limit using spICP-MS and then apply it to
nanoparticles composed of 40 different elements. The calculated Dmin values
correspond well for a few of the elements with their detectable sizes that are
available in the literature. Assuming each nanoparticle sample is composed of one
element, Dmin values vary substantially among the 40 elements: Ta, U, Ir, Rh, Th,
Ce, and Hf showed the lowest Dmin values, <=10 nm; Bi, W, In, Pb, Pt, Ag, Au, Tl,
Pd, Y, Ru, Cd, and Sb had Dmin in the range of 11-20 nm; Dmin values of Co, Sr,
Sn, Zr, Ba, Te, Mo, Ni, V, Cu, Cr, Mg, Zn, Fe, Al, Li, and Ti were located at 21
80 nm; and Se, Ca, and Si showed high Dmin values, greater than 200 nm. A range
of parameters that influence the Dmin, such as instrument sensitivity,
nanoparticle density, and background noise, is demonstrated. It is observed that,
when the background noise is low, the instrument sensitivity and nanoparticle
density dominate the Dmin significantly. Approaches for reducing the Dmin, e.g.,
collision cell technology (CCT) and analyte isotope selection, are also
discussed. To validate the Dmin estimation approach, size distributions for three
engineered nanoparticle samples were obtained using spICP-MS. The use of this
methodology confirms that the observed minimum detectable sizes are consistent
with the calculated Dmin values. Overall, this work identifies the elements and
nanoparticles to which current spICP-MS approaches can be applied, in order to
enable quantification of very small nanoparticles at low concentrations in
aqueous media.
PMID- 25122541
TI - High open circuit voltage in regioregular narrow band gap polymer solar cells.
AB - The regioregular narrow band gap (E(g) ~1.5 eV) conjugated polymer PIPCP was
designed and synthesized. PIPCP contains a backbone comprised of CPDT-PT-IDT-PT
repeat units (CPDT = cyclopentadithiophene, PT = pyridyl[2,1,3]thiadiazole, IDT =
indacenodithiophene) and strictly organized PT orientations, such that the
pyridyl N-atoms point toward the CPDT fragment. Comparison of PIPCP with the
regiorandom counterpart PIPC-RA illustrates that the higher level of molecular
order translates to higher power conversion efficiencies (PCEs) when incorporated
into bulk heterojunction (BHJ) organic solar cells. Examination of thin films via
absorption spectroscopy and grazing incidence wide-angle X-ray diffraction
(GIWAXS) experiments provides evidence of higher order within thin films obtained
by spin coating. Most significantly, we find that PIPCP:PC61BM blends yield
devices with an open circuit voltage (V(oc)) of 0.86 V, while maintaining a PCE
of ~6%. Comparison against a wide range of analogous narrow band gap conjugated
polymers reveals that this V(oc) value is particularly high for a BHJ system with
band gaps in the 1.4-1.5 eV range thereby indicating a very low E(g) - eV(oc)
loss.
PMID- 25122542
TI - Systematic variation of gel-phase texture in phospholipid membranes.
AB - The tilted gel phase of lipid bilayers can display in-plane orientational texture
due to long-range alignment of the molecular director. We explore systematic
variations of texture defects in a series of binary phospholipid membranes. Using
polarized two-photon fluorescence microscopy, the texture pattern of single
domains is revealed. The appearance of a central vortex-type defect in each
domain correlates with a particular range of hydrophobic mismatch values h > 1 nm
at the domain border while domains with h < 1 nm correlate with uniformly aligned
texture. The central vortex defect is characterized by a defect angle, indicating
its bend or splay nature. Using image analysis, we measure the defect angle and
find that it has primarily bend character for small mismatch values (h ~ 1 nm)
and primarily splay nature for larger values of h. For domains containing a
vortex, the domain shape is decoupled from the texture while for uniformly
textured domains there is a preferred texture orientation of ?45 degrees along
the domain border. The results establish a foundation for understanding texture
phenomena in compositionally complex membranes.
PMID- 25122539
TI - Patterns of admixture and population structure in native populations of Northwest
North America.
AB - The initial contact of European populations with indigenous populations of the
Americas produced diverse admixture processes across North, Central, and South
America. Recent studies have examined the genetic structure of indigenous
populations of Latin America and the Caribbean and their admixed descendants,
reporting on the genomic impact of the history of admixture with colonizing
populations of European and African ancestry. However, relatively little genomic
research has been conducted on admixture in indigenous North American
populations. In this study, we analyze genomic data at 475,109 single-nucleotide
polymorphisms sampled in indigenous peoples of the Pacific Northwest in British
Columbia and Southeast Alaska, populations with a well-documented history of
contact with European and Asian traders, fishermen, and contract laborers. We
find that the indigenous populations of the Pacific Northwest have higher gene
diversity than Latin American indigenous populations. Among the Pacific Northwest
populations, interior groups provide more evidence for East Asian admixture,
whereas coastal groups have higher levels of European admixture. In contrast with
many Latin American indigenous populations, the variance of admixture is high in
each of the Pacific Northwest indigenous populations, as expected for recent and
ongoing admixture processes. The results reveal some similarities but notable
differences between admixture patterns in the Pacific Northwest and those in
Latin America, contributing to a more detailed understanding of the genomic
consequences of European colonization events throughout the Americas.
PMID- 25122543
TI - Marked anti-tumor effects of CD8(+)CD62L(+) T cells from melanoma-bearing mice.
AB - CD8(+)CD62L(+) T cells have been shown to play pivotal roles in anti-viral
immunity, chronic myeloid leukemia and renal cell carcinoma. Recently,
CD8(+)CD62L(+) T cells from naive mice (nCD8(+)CD62L(+) T cells) have shown
superior anti-tumor properties in melanoma-bearing mice. Considering that antigen
specific memory T cells have shown to possess more potent immunity than non
specific memory T cells, we hypothesized that CD8(+)CD62L(+) T cells from tumor
bearing individuals (mCD8(+)CD62L(+) T cells) might have superior anti-tumor
effect than nCD8(+)CD62L(+) T cells. Therefore, we investigated phenotypes,
functions and the in vivo distribution of mCD8(+)CD62L(+) T cells in tumor
bearing mice. We found that, while keeping the features of central memory T
cells, the frequency of mCD8(+)CD62L(+) T cell in the spleen of tumor-bearing
mice was significantly higher than that the one of nCD8(+)CD62L(+) T cell in
naive mice. Moreover, we demonstrated that mCD8(+)CD62L(+) T cells had higher
proliferation rate and IFN-gamma production than nCD8(+)CD62L(+) T cells, in
vitro. We performed adoptive transfer of mCD8(+)CD62L(+) T cells into melanoma
bearing mice and tracked them in spleen, lymph nodes and in melanoma tissues. Our
results show that mCD8(+)CD62L(+) T cells had stronger in vivo anti-tumoral
activity than nCD8(+)CD62L(+) T cells. This study highlights the therapeutic
potential of mCD8(+)CD62L(+) T cells in the immunotherapy of melanoma and
possibly other tumors.
PMID- 25122545
TI - Italy between drinking culture and control policies for alcoholic beverages.
AB - This paper focuses on whether the on-going dramatic decrease in alcohol
consumption in Italy, especially of wine, during 1961-2008, was associated with
which parallel sociodemographic and economic changes and with alcohol control
policies. The study, using both time series (TS) and artificial neural network
(ANN)-based analyses documents that its selected sociodemographic and economic
factors, and particularly urbanization, had a definite connection with wine
consumption decrease, spirits decrease, and the increase in beer consumption over
time. On the other hand, control policies showed no effect on the decline in
alcohol consumption, since no alcohol control policy existed in Italy between
1960 and 1987. A few policies introduced since 1988 (BAC and sale restrictions
during mass events) may have contributed to reducing or to maintaining the on
going reduction. Study limitations are noted and future needed research is
suggested.
PMID- 25122546
TI - Asymmetrical distribution of choline phospholipids revealed by click chemistry
and freeze-fracture electron microscopy.
AB - Choline-containing phospholipids (Cho-PLs) are major components of all cellular
membranes. We developed an electron microscopic technique to investigate the
poorly understood problem of how Cho-PLs are distributed between membrane
leaflets. Our method relies on generating freeze-fracture replicas of cells
metabolically labeled with the choline analog, propargylcholine, followed by
"click" reaction to conjugate biotin to propargylcholine head groups, and
immunodetection of biotin with colloidal gold. Using this method in budding
yeast, we found that, surprisingly, the Golgi and plasma membrane display a
cytoplasmic leaflet-dominant asymmetry in Cho-PL distribution; in contrast, Cho
PLs are evenly distributed between the exoplasmic and cytoplasmic leaflets of
other organelle membranes. In mammalian culture cells, the plasma membrane shows
symmetrical Cho-PL distribution between leaflets, suggesting a fundamental
difference between yeast and mammals. Our method should be expandable to other
classes of lipids and will be useful for deciphering the mechanism responsible
for generating lipid asymmetry in biological membranes.
PMID- 25122547
TI - Evaluation of chirp reversal power modulation sequence for contrast agent
imaging.
AB - Over the last decade, significant research effort has been focused on the use of
chirp for contrast agent imaging because chirps are known to significantly
increase imaging contrast-to-noise ratio (CNR). New imaging schemes, such as
chirp reversal (CR), have been developed to improve contrast detection by
increasing non-linear microbubble responses. In this study we evaluated the
contrast enhancement efficiency of various chirped imaging sequences in
combination with well-established imaging schemes such as power modulation (PM)
and pulse inversion (PI). The imaging schemes tested were implemented on a fully
programmable open scanner and evaluated by ultrasonically scanning (excitation
frequency of 2.5 MHz; amplitude of 350 kPa) a tissue-mimicking flow phantom
comprising a 4 mm diameter tube through which aqueous dispersions (dilution
fraction of 1/2000) of the commercial ultrasound contrast agent, SonoVue((r))
were continuously circulated. The recovery of non-linear microbubble responses
after chirp compression requires the development and the optimization of a
specific filter. A compression filter was therefore designed and used to compress
and extract several non-linear components from the received microbubble
responses. The results showed that using chirps increased the image CNR by
approximately 10 dB, as compared to conventional Gaussian apodized sine burst
excitation but degraded the axial resolution by a factor of 1.4, at -3 dB. We
demonstrated that the highest CNR and contrast-to-noise ratio (CTR) were
achievable when CR was combined with PM as compared to other imaging schemes such
as PI.
PMID- 25122544
TI - Cyclotorsional and non-cyclotorsional components of eye rotation observed from
sitting to supine position.
AB - PURPOSE: Evaluate average cyclotorsional and non-cyclotorsional components (NCY)
of eye rotation from sitting to supine, and associate average cyclotorsion to
different variables. METHODS: Medical records of patients who underwent bilateral
sequential laser refractive surgery were retrospectively evaluated. Recorded
variables included the patient's age, refraction, automated keratometry, pupil
displacement and eye rotation from sitting to supine position. Measured iris
rotation (total rotation, TR) was decomposed into two components: NCY, defined as
the common rotation component of each eye of the same patient, and cyclotorsional
component (CY), defined as the assumed independent eye rotation for each eye in
relation to the face, so that TR=NCY+CY. Cyclotorsion ratio (CR) was calculated
as CR=|CY|/|TR|, and used to correlate CY with TR for each eye. RESULTS: Data
from 310 eyes of 155 patients were evaluated. TR was +1.43 degrees +/-3.41
degrees (-8.30 degrees to +9.20 degrees ). Average CYs and NCYs per patient
were +1.43 degrees +/-2.04 degrees (-3.15+/- to +7.40 degrees ) and -0.28
degrees +/-2.72 degrees (-6.85 degrees to +7.15 degrees ), respectively. TR
demonstrated that 40.6% and 8.4% of patients presented bilateral excyclotorsion
and incyclotorsion, respectively. When excluding NCYs, average CYs demonstrated
that 74.2% of patients presented excyclotorsion and 23.9% presented
incyclotorsion. CR demonstrated that TR represented from 75% to 125% of average
CY in 19.68% of the eyes. TR overestimated and underestimated average CYs above
these limits in 52.26% and 28.06% of the eyes, respectively. There was no
statistical association between average CYs and the different variables.
DISCUSSION: This study demonstrates that most of the rotations previously
attributed to torsional components were probably due to NCYs, such as postural
misalignments. Apparently, the amplitude of cyclotorsional movements is smaller
than observed in previous reports, and could not be associated with any studied
variable.
PMID- 25122548
TI - Computed tomography-guided C2 pedicle screw placement for treatment of unstable
hangman fractures.
AB - STUDY DESIGN: Case series and description of technique. OBJECTIVE: The purpose of
this study was to evaluate the feasibility and accuracy of inserting pedicle
screws in unstable Hangman fracture cases by using intraoperative CT (O-arm)
based navigation. SUMMARY OF BACKGROUND DATA: Hangman fracture, also known as
traumatic spondylolisthesis of the C2, is defined as a fracture involving the
lamina, articular facets, pedicles, or pars of the axis vertebra. Opinions vary
regarding the optimal treatment of unstable Hangman fractures. Some authors have
recommended the use of rigid orthosis, whereas others have recommended surgical
stabilization. The peculiar anatomy of the upper cervical spine is highly
variable, and the presence of surrounding neurovascular structures makes pedicle
screw fixation even more technically challenging. The advent of intraoperative 3
dimensional navigation systems permits safe and accurate instrumentation of the
cervical spine. METHODS: Ten patients with unstable Hangman fracture, with age
ranging from 17 years to 81 years, were operated under O-arm-based navigation,
and screw position was confirmed with intraoperative computed tomographic scan.
RESULTS: A total of 52 screws were inserted under O-arm guidance: 20 in C2
pedicle, 20 in C3 lateral mass, and rest in C4 lateral mass. Screw misplacement
was seen in only 1 C2 pedicle screw (1 of 20, 5%). No new-onset neurological
deficit developed in any of the patients. Follow-up ranged from 3 months to 21
months. Bony fusion was achieved in all. Full rotation was preserved at C1-C2
joint. All the patients (50%) with neurological deficits before surgery improved
after surgery. CONCLUSION: This series demonstrates that C2 pedicle screws can be
put with precision under O-arm-guided navigation, and intraoperative computed
tomographic scan can confirm position of screws. Patients can be operated and
mobilized early with negligible risk of screw misplacement, with preservation of
motion at the C1-C2 joint. LEVEL OF EVIDENCE: 4.
PMID- 25122551
TI - Prevalence and risk factors of respiratory symptoms among home-based garment
workers in Bangkok, Thailand.
AB - This study aimed to determine the prevalence and risk factors associated with
respiratory symptoms. A cross-sectional study with random sampling method was
employed and 300 home-based garment workers (HBGWs) were recruited. Risk factors,
including personal factors; knowledge, health preventive behaviors, and skill of
self-health surveillance, working condition, and respiratory symptoms were
assessed. Data were collected using self-reported questionnaires. Prevalence of
respiratory symptom was 22.3%. Majority of participants were female (78%). Mean
age and working experience were 37.38 years (SD = 10.70) and 13.58 years (SD =
8.71), respectively. Allergic respiratory symptoms (odds ratio [OR] = 16.5; 95%
confidence interval [CI] = 8.61-31.7) and garment dust exposure (OR = 12.3; 95%
CI = 6.49-23.3) were significantly associated with respiratory symptoms (P <
.001). Logistic regression analysis indicated history of allergic predicted the
respiratory symptoms (OR = 12.96; 95% CI = 4.24-39.55). HBGWs who had serious
allergic symptoms and high exposure to dust were at risk of respiratory symptoms.
Therefore, preventive program for garment dust exposure among HBGWs is needed.
PMID- 25122552
TI - Assessment of internalized stigma among patients with mental disorders in
Thiruvananthapuram district, Kerala, India.
AB - This study aims to compare the prevalence of high internalized stigma of mental
illness among patients attending community-based and psychiatric hospital-based
care in Thiruvananthapuram district, Kerala, India and to examine the factors
associated with high internalized stigma. A cross-sectional survey was conducted
among 290 patients, mean age 45 years, 38.2% and 61.8% female. A Malayalam
version of the Internalized Stigma of Mental Illness inventory was used for
assessing internalized stigma. A multistage random sampling method was adopted.
The prevalence of high internalized stigma was higher among patients from
community-based care (44.7%) as compared with those from psychiatric hospital
based care (34.1%). Apart from treatment in community-based care, age <= 45
years, unemployment, absence of long-term friendships, no hope of cure with
medication, presence of other illnesses, and substance use were significantly
associated with high internalized stigma. More than one third of the subjects had
high internalized stigma.
PMID- 25122550
TI - Cooperativity to increase Turing pattern space for synthetic biology.
AB - It is hard to bridge the gap between mathematical formulations and biological
implementations of Turing patterns, yet this is necessary for both understanding
and engineering these networks with synthetic biology approaches. Here, we model
a reaction-diffusion system with two morphogens in a monostable regime, inspired
by components that we recently described in a synthetic biology study in
mammalian cells.1 The model employs a single promoter to express both the
activator and inhibitor genes and produces Turing patterns over large regions of
parameter space, using biologically interpretable Hill function reactions. We
applied a stability analysis and identified rules for choosing biologically
tunable parameter relationships to increase the likelihood of successful
patterning. We show how to control Turing pattern sizes and time evolution by
manipulating the values for production and degradation relationships. More
importantly, our analysis predicts that steep dose-response functions arising
from cooperativity are mandatory for Turing patterns. Greater steepness increases
parameter space and even reduces the requirement for differential diffusion
between activator and inhibitor. These results demonstrate some of the
limitations of linear scenarios for reaction-diffusion systems and will help to
guide projects to engineer synthetic Turing patterns.
PMID- 25122554
TI - Matrix metalloproteinase 9-mediated shedding of syndecan 4 in response to tumor
necrosis factor alpha: a contributor to endothelial cell glycocalyx dysfunction.
AB - The endothelial surface glycocalyx is a hydrated mesh in which proteoglycans are
prominent. It is damaged in diseases associated with elevated levels of tumor
necrosis factor alpha (TNF-alpha). We investigated the mechanism of TNF-alpha
induced disruption of the glomerular endothelial glycocalyx. We used
conditionally immortalized human glomerular endothelial cells (GEnCs),
quantitative PCR arrays, Western blotting, immunoprecipitation,
immunofluorescence, and dot blots to examine the effects of TNF-alpha. TNF-alpha
induced syndecan 4 (SDC4) mRNA up-regulation by 2.5-fold, whereas cell surface
SDC4 and heparan sulfate (HS) were reduced by 36 and 30%, respectively, and SDC4
and sulfated glycosaminoglycan in the culture medium were increased by 52 and
65%, respectively, indicating TNF-alpha-induced shedding. Small interfering
(siRNA) knockdown of SDC4 (by 52%) caused a corresponding loss of cell surface HS
of similar magnitude (38%), and immunoprecipitation demonstrated that SDC4 and HS
are shed as intact proteoglycan ectodomains. All of the effects of TNF-alpha on
SDC4 and HS were abrogated by the metalloproteinase (MMP) inhibitor batimastat.
Also abrogated was the associated 37% increase in albumin passage across GEnC
monolayers. Specific MMP9 knockdown by siRNA similarly blocked TNF-alpha effects.
SDC4 is the predominant HS proteoglycan in the GEnC glycocalyx. TNF-alpha-induced
MMP9-mediated shedding of SDC4 is likely to contribute to the endothelial
glycocalyx disruption observed in diabetes and inflammatory states.
PMID- 25122553
TI - Activation of EPAC1/2 is essential for osteoclast formation by modulating
NFkappaB nuclear translocation and actin cytoskeleton rearrangements.
AB - Bisphosphonates inhibit osteoclast differentiation/function via inhibition of
Rap1A isoprenylation. As Rap1 is the effector of exchange protein directly
activated by cAMP (EPAC) proteins, we determined the role of EPAC in osteoclast
differentiation. We examined osteoclast differentiation as the number of primary
murine/human bone-marrow precursors that differentiated into multinucleated TRAP
positive cells in the presence of EPAC-selective stimulus (8-pCTP-2'-O-Me-cAMP,
100 MUM; 8-pCTP-2'-O-Me-cAMP-AM, 1 MUM) or inhibitor brefeldin A (BFA), ESI-05,
and ESI-09 (10 MUM each). Rap1 activity was assessed, and signaling events, as
well as differentiation in EPAC1/2-knockdown RAW264.7 cells, were studied. Direct
EPAC1/2 stimulation significantly increased osteoclast differentiation, whereas
EPAC1/2 inhibition diminished differentiation (113 +/- 6%, P < 0.05, and 42 +/-
10%, P < 0.001, of basal, respectively). Rap1 activation was maximal 15 min after
RANKL stimulation (147 +/- 9% of basal, P < 0.001), whereas silencing of EPAC1/2
diminished activated Rap1 (43 +/- 13 and 20 +/- 15% of control, P < 0.001) and
NFkB nuclear translocation. TRAP-staining revealed no osteoclast differentiation
in EPAC1/2-KO cells. Cathepsin K, NFATc1, and osteopontin mRNA expression
decreased in EPAC1/2-KO cells when compared to control. RhoA, cdc42, Rac1, and
FAK were activated in an EPAC1/2-dependent manner, and there was diminished
cytoskeletal assembly in EPAC1/2-KO cells. In summary, EPAC1 and EPAC2 are
critical signaling intermediates in osteoclast differentiation that permit RANKL
stimulated NFkB nuclear translocation and actin rearrangements. Targeting this
signaling intermediate may diminish bone destruction in inflammatory arthritis.
PMID- 25122555
TI - Low tendon stiffness and abnormal ultrastructure distinguish classic Ehlers
Danlos syndrome from benign joint hypermobility syndrome in patients.
AB - There is a clinical overlap between classic Ehlers-Danlos syndrome (cEDS) and
benign joint hypermobility syndrome (BJHS), with hypermobility as the main
symptom. The purpose of this study was to investigate the role of type V collagen
mutations and tendon pathology in these 2 syndromes. In patients (cEDS, n=7;
BJHS, n=8) and controls (Ctrl, n=8), we measured patellar tendon ultrastructure
(transmission electron microscopy), dimensions (magnetic resonance imaging), and
biomechanical properties (force and ultrasonographic measurements during a ramped
isometric knee extension). Mutation analyses (COL5A1 and COL5A2) were performed
in the patients. COL5A1 mutations were found in 3 of 4 of the patients with cEDS.
Patellar tendon dimensions were similar between the groups, but large, irregular
collagen fibrils were in 4 of 5 patients with cEDS. In the cEDS group, tendon
stiffness and Young's modulus were reduced to ~50% of that in BJHS and Ctrl
groups (P<0.05). The nonhypermobile, healthy controls were matched with the
patients in age, sex, body weight, and physical activity, to compare outcomes.
COL5A1 mutations led to structural tendon pathology and low tendon stiffness in
cEDS, explaining the patients' hypermobility, whereas no tendon pathology was
found that explained the hypermobility in BJHS.
PMID- 25122557
TI - Disuse deterioration of human skeletal muscle challenged by resistive exercise
superimposed with vibration: evidence from structural and proteomic analysis.
AB - In the present bed rest (BR) study, 23 volunteers were randomized into 3
subgroups: 60 d BR control (Ctr); BR with resistive exercise (RE; lower-limb
load); and resistive vibration exercise (RVE; RE with superimposed vibration).
The aim was to analyze by confocal and electron microscopy the effects of
vibration on myofibril and filament integrity in soleus (Sol) and vastus
lateralis (VL) muscle; differential proteomics of contractile, cytoskeletal, and
costameric proteins (TN-C, ROCK1, and FAK); and expression of PGC1alpha and
atrophy-related master genes MuRF1 and MuRF2. RVE (but not RE) preserved myofiber
size and phenotype in Sol and VL by overexpressing MYBPC1 (42%, P <= 0.01), WDR1
(39%, P <= 0.01), sarcosin (84%, P <= 0.01), and CKM (20%, P <= 0.01) and
prevented myofibrillar ultrastructural damage as detectable by MuRF1 expression.
In Sol, cytoskeletal and contractile proteins were normalized by RVE, and TN-C
increased (59%, P <= 0.01); the latter also with RE (108%, P <= 0.01). In VL, the
outcomes of both RVE (acting on sarcosin and desmin) and RE (by way of troponinT
slow and MYL2) were similar. RVE appears to be a highly efficient countermeasure
protocol against muscle atrophy and ultrastructural and molecular dysregulation
induced by chronic disuse.
PMID- 25122556
TI - Long-acting antituberculous therapeutic nanoparticles target macrophage
endosomes.
AB - Eradication of Mycobacterium tuberculosis (MTB) infection requires daily
administration of combinations of rifampin (RIF), isoniazid
[isonicotinylhydrazine (INH)], pyrazinamide, and ethambutol, among other drug
therapies. To facilitate and optimize MTB therapeutic selections, a mononuclear
phagocyte (MP; monocyte, macrophage, and dendritic cell)-targeted drug delivery
strategy was developed. Long-acting nanoformulations of RIF and an INH
derivative, pentenyl-INH (INHP), were prepared, and their physicochemical
properties were evaluated. This included the evaluation of MP particle uptake and
retention, cell viability, and antimicrobial efficacy. Drug levels reached 6
MUg/10(6) cells in human monocyte-derived macrophages (MDMs) for nanoparticle
treatments compared with 0.1 MUg/10(6) cells for native drugs. High RIF and INHP
levels were retained in MDM for >15 d following nanoparticle loading. Rapid loss
of native drugs was observed in cells and culture fluids within 24 h.
Antimicrobial activities were determined against Mycobacterium smegmatis (M.
smegmatis). Coadministration of nanoformulated RIF and INHP provided a 6-fold
increase in therapeutic efficacy compared with equivalent concentrations of
native drugs. Notably, nanoformulated RIF and INHP were found to be localized in
recycling and late MDM endosomal compartments. These were the same compartments
that contained the pathogen. Our results demonstrate the potential of
antimicrobial nanomedicines to simplify MTB drug regimens.
PMID- 25122559
TI - Fixing the troubled mental health system.
PMID- 25122560
TI - The community care chest is running out of cards.
PMID- 25122561
TI - Introducing the foundation Chair of the new Division of Ecoimmunology and Disease
Ecology.
PMID- 25122558
TI - Protective role of macrophage migration inhibitory factor in nonalcoholic
steatohepatitis.
AB - MIF is an inflammatory cytokine but is hepatoprotective in models of hepatotoxin
induced liver fibrosis. Hepatic fibrosis can also develop from metabolic liver
disease, such as nonalcoholic fatty liver disease (NASH). We investigated the
role of MIF in high-fat or methionine- and choline-deficient diet mouse models of
NASH. Mif(-/-) mice showed elevated liver triglyceride levels (WT, 53+/-14 mg/g
liver; Mif(-/-), 103+/-7 mg/g liver; P<0.05) and a 2-3-fold increased expression
of lipogenic genes. Increased fatty degeneration in the livers of Mif(-/-) mice
was associated with increased hepatic inflammatory cells (1.6-fold increase in
F4/80(+) macrophages) and proinflammatory cytokines (e.g., 2.3-fold increase in
Tnf-alpha and 2-fold increase in Il-6 expression). However, inflammatory cells
and cytokines were decreased by 50-90% in white adipose tissue (WAT) of Mif(-/-)
mice. Subset analysis showed that macrophage phenotypes in livers of Mif(-/-)
mice were skewed toward M2 (e.g., 1.7-fold and 2.5-fold increase in Arg1 and Il
13, respectively, and 2.5-fold decrease in iNos), whereas macrophages were
generally reduced in WAT of these mice (70% reduction in mRNA expression of
F4/80(+) macrophages). The protective MIF effect was scrutinized in isolated
hepatocytes. MIF reversed inflammation-induced triglyceride accumulation in Hepa1
6 cells and primary hepatocytes and also attenuated oleic acid-elicited
triglyceride increase in 3T3-L1 adipocytes. Protection from fatty hepatocyte
degeneration was paralleled by a 2- to 3-fold reduction by MIF of hepatocyte
proinflammatory cytokine production. Blockade of MIF receptor cluster of
differentiation 74 (CD74) but not of CXCR2 or CXCR4 fully reverted the protective
effect of MIF, comparable to AMPK inhibition. In summary, we demonstrate that MIF
mediates hepatoprotection through the CD74/AMPK pathway in hepatocytes in
metabolic models of liver injury.
PMID- 25122562
TI - Small primary care physician practices have low rates of preventable hospital
admissions.
AB - Nearly two-thirds of US office-based physicians work in practices of fewer than
seven physicians. It is often assumed that larger practices provide better care,
although there is little evidence for or against this assumption. What is the
relationship between practice size--and other practice characteristics, such as
ownership or use of medical home processes--and the quality of care? We conducted
a national survey of 1,045 primary care-based practices with nineteen or fewer
physicians to determine practice characteristics. We used Medicare data to
calculate practices' rate of potentially preventable hospital admissions
(ambulatory care-sensitive admissions). Compared to practices with 10-19
physicians, practices with 1-2 physicians had 33 percent fewer preventable
admissions, and practices with 3-9 physicians had 27 percent fewer. Physician
owned practices had fewer preventable admissions than hospital-owned practices.
In an era when health care reform appears to be driving physicians into larger
organizations, it is important to measure the comparative performance of
practices of all sizes, to learn more about how small practices provide patient
care, and to learn more about the types of organizational structures--such as
independent practice associations--that may make it possible for small practices
to share resources that are useful for improving the quality of care.
PMID- 25122563
TI - Different phase behavior and packing of ceramides with long (C16) and very long
(C24) acyls in model membranes: infrared spectroscopy using deuterated lipids.
AB - Ceramides (Cer) are the central molecules in sphingolipid metabolism that
participate in cellular signaling and also prevent excessive water loss by the
skin. Previous studies showed that sphingosine-based Cer with a long 16C chain
(CerNS16) and very long 24C-chain ceramides (CerNS24) differ in their biological
actions. Increased levels of long CerNS16 at the expense of the very long CerNS24
have been found in atopic dermatitis patients, and this change correlated with
the skin barrier properties. To probe the membrane behavior of the long CerNS16
and the very long chain CerNS24, we studied their interactions with fatty acids
and cholesterol in model stratum corneum membranes using infrared spectroscopy.
Using Cer with deuterated acyls and/or deuterated fatty acids, we showed
differences in lipid mixing, packing, and thermotropic phase behavior between
long and very long Cer. These differences were observed in the presence of
lignoceric acid or a heterogeneous fatty acid mixture (C16-C24), in the presence
or absence of cholesterol sulfate, and at 5-95% humidity. In these membranes,
very long CerNS24 prefers an extended (splayed-chain) conformation in which the
fatty acid is associated with the very long Cer chain. In contrast, the shorter
CerNS16 and fatty acids are mostly phase separated.
PMID- 25122564
TI - Pharmacokinetic modeling of the subcutaneous absorption of therapeutic proteins.
AB - Subcutaneous injection is an important route of administration for therapeutic
proteins that provides several advantages over other modes of parenteral
delivery. Despite extensive clinical use, the exact mechanism underlying
subcutaneous absorption of proteins is not completely understood, and the
accuracy of prediction of absorption of biotherapeutics in humans remains
unsatisfactory. This review summarizes a variety of models that have been
developed for describing the pharmacokinetics of therapeutic proteins
administered by subcutaneous injection, including single- and dual-pathway
absorption models. Modeling of the lymphatic uptake and redistribution,
absorption of monoclonal antibodies and insulin, and population analysis of
protein absorption are discussed. The review also addresses interspecies modeling
and prediction of absorption in humans, highlights important factors affecting
the absorption processes, and suggests approaches for future development of
mechanism-based absorption models.
PMID- 25122566
TI - Joint removal of random and fixed-pattern noise through spatiotemporal video
filtering.
AB - We propose a framework for the denoising of videos jointly corrupted by spatially
correlated (i.e., nonwhite) random noise and spatially correlated fixed-pattern
noise. Our approach is based on motion-compensated 3D spatiotemporal volumes,
i.e., a sequence of 2D square patches extracted along the motion trajectories of
the noisy video. First, the spatial and temporal correlations within each volume
are leveraged to sparsify the data in 3D spatiotemporal transform domain, and
then the coefficients of the 3D volume spectrum are shrunk using an adaptive 3D
threshold array. Such array depends on the particular motion trajectory of the
volume, the individual power spectral densities of the random and fixed-pattern
noise, and also the noise variances which are adaptively estimated in transform
domain. Experimental results on both synthetically corrupted data and real
infrared videos demonstrate a superior suppression of the random and fixed
pattern noise from both an objective and a subjective point of view.
PMID- 25122565
TI - In vitro assay of six UDP-glucuronosyltransferase isoforms in human liver
microsomes, using cocktails of probe substrates and liquid chromatography-tandem
mass spectrometry.
AB - UDP-glucuronosyltransferase (UGT)-mediated drug-drug interactions are commonly
evaluated during drug development. We present a validated method for the
simultaneous evaluation of drug-mediated inhibition of six major UGT isoforms,
developed in human liver microsomes through the use of pooled specific UGT probe
substrates (cocktail assay) and rapid liquid chromatography-tandem mass
spectrometry (LC-MS/MS) analysis. The six probe substrates used in this assay
were estradiol (UGT1A1), chenodeoxycholic acid (UGT1A3), trifluoperazine
(UGT1A4), 4-hydroxyindole (UGT1A6), propofol (UGT1A9), and naloxone (UGT2B7). In
a cocktail incubation, UGT1A1, UGT1A9, and UGT2B7 activities were substantially
inhibited by other substrates. This interference could be eliminated by dividing
substrates into two incubations: one containing estradiol, trifluoperazine, and 4
hydroxyindole, and the other containing chenodeoxycholic acid, propofol, and
naloxone. Incubation mixtures were pooled for the simultaneous analysis of
glucuronyl conjugates in a single LC-MS/MS run. The optimized cocktail method was
further validated against single-probe substrate assays using compounds known to
inhibit UGTs. The degree of inhibition of UGT isoform activities by such known
inhibitors in this cocktail assay was not substantially different from that in
single-probe assays. This six-isoform cocktail assay may be very useful in
assessing the UGT-based drug-interaction potential of candidates in a drug
discovery setting.
PMID- 25122567
TI - Incremental N-mode SVD for large-scale multilinear generative models.
AB - Tensor decomposition is frequently used in image processing and machine learning
for its ability to express higher order characteristics of data. Among tensor
decomposition methods, N-mode singular value decomposition (SVD) is widely used
owing to its simplicity. However, the data dimension often becomes too large to
perform N-mode SVD directly due to memory limitation. An incremental method to N
mode SVD can be used to resolve this issue, but existing approaches only provide
a result, which is just enough to solve discriminative problems, not the full
factorization result. In this paper, we present a complete derivation of the
incremental N-mode SVD, which can be applied to generative models, accompanied by
a technique that can reduce the computational cost by reordering calculations.
The proposed incremental N-mode SVD can also be used effectively to update the
current result of N-mode SVD when new training data is received. The proposed
method provides a very good approximation of N -mode SVD for the experimental
data, and requires much less computation in updating a multilinear model.
PMID- 25122568
TI - A novel video dataset for change detection benchmarking.
AB - Change detection is one of the most commonly encountered low-level tasks in
computer vision and video processing. A plethora of algorithms have been
developed to date, yet no widely accepted, realistic, large-scale video data set
exists for benchmarking different methods. Presented here is a unique change
detection video data set consisting of nearly 90 000 frames in 31 video sequences
representing six categories selected to cover a wide range of challenges in two
modalities (color and thermal infrared). A distinguishing characteristic of this
benchmark video data set is that each frame is meticulously annotated by hand for
ground-truth foreground, background, and shadow area boundaries-an effort that
goes much beyond a simple binary label denoting the presence of change. This
enables objective and precise quantitative comparison and ranking of video-based
change detection algorithms. This paper discusses various aspects of the new data
set, quantitative performance metrics used, and comparative results for over two
dozen change detection algorithms. It draws important conclusions on solved and
remaining issues in change detection, and describes future challenges for the
scientific community. The data set, evaluation tools, and algorithm rankings are
available to the public on a website and will be updated with feedback from
academia and industry in the future.
PMID- 25122569
TI - DEB: definite error bounded tangent estimator for digital curves.
AB - We propose a simple and fast method for tangent estimation of digital curves.
This geometric-based method uses a small local region for tangent estimation and
has a definite upper bound error for continuous as well as digital conics, i.e.,
circles, ellipses, parabolas, and hyperbolas. Explicit expressions of the upper
bounds for continuous and digitized curves are derived, which can also be applied
to nonconic curves. Our approach is benchmarked against 72 contemporary tangent
estimation methods and demonstrates good performance for conic, nonconic, and
noisy curves. In addition, we demonstrate a good multigrid and isotropic
performance and low computational complexity of O(1) and better performance than
most methods in terms of maximum and average errors in tangent computation for a
large variety of digital curves.
PMID- 25122570
TI - Interacting geometric priors for robust multimodel fitting.
AB - Recent works on multimodel fitting are often formulated as an energy minimization
task, where the energy function includes fitting error and regularization terms,
such as low-level spatial smoothness and model complexity. In this paper, we
introduce a novel energy with high-level geometric priors that consider
interactions between geometric models, such that certain preferred model
configurations may be induced.We argue that in many applications, such prior
geometric properties are available and should be fruitfully exploited. For
example, in surface fitting to point clouds, the building walls are usually
either orthogonal or parallel to each other. Our proposed energy function is
useful in dealing with unknown distributions of data errors and outliers, which
are often the factors leading to biased estimation. Furthermore, the energy can
be efficiently minimized using the expansion move method. We evaluate the
performance on several vision applications using real data sets. Experimental
results show that our method outperforms the state-of-the-art methods without
significant increase in computation.
PMID- 25122571
TI - Sharing visual secrets in single image random dot stereograms.
AB - Visual cryptography schemes (VCSs) generate random and meaningless shares to
share and protect secret images. Conventional VCSs suffer from a transmission
risk problem because the noise-like shares will raise the suspicion of attackers
and the attackers might intercept the transmission. Previous research has
involved in hiding shared content in halftone shares to reduce these risks, but
this method exacerbates the pixel expansion problem and visual quality
degradation problem for recovered images. In this paper, a binocular VCS (BVCS),
called the (2,n)-BVCS, and an encryption algorithm are proposed to hide the
shared pixels in the single image random dot stereograms (SIRDSs). Because the
SIRDSs have the same 2D appearance as the conventional shares of a VCS, this
paper tries to use SIRDSs as cover images of the shares of VCSs to reduce the
transmission risk of the shares. The encryption algorithm alters the random dots
in the SIRDSs according to the construction rule of the (2,n)-BVCS to produce
nonpixel-expansion shares of the BVCS. Altering the dots in a SIRDS will degrade
the visual quality of the reconstructed 3D objects. Hence, we propose an
optimization model that is based on the visual quality requirement of SIRDSs to
develop construction rules for a (2,n)-BVCS that maximize the contrast of the
recovered image in the BVCS.
PMID- 25122572
TI - VSI: a visual saliency-induced index for perceptual image quality assessment.
AB - Perceptual image quality assessment (IQA) aims to use computational models to
measure the image quality in consistent with subjective evaluations. Visual
saliency (VS) has been widely studied by psychologists, neurobiologists, and
computer scientists during the last decade to investigate, which areas of an
image will attract the most attention of the human visual system. Intuitively, VS
is closely related to IQA in that suprathreshold distortions can largely affect
VS maps of images. With this consideration, we propose a simple but very
effective full reference IQA method using VS. In our proposed IQA model, the role
of VS is twofold. First, VS is used as a feature when computing the local quality
map of the distorted image. Second, when pooling the quality score, VS is
employed as a weighting function to reflect the importance of a local region. The
proposed IQA index is called visual saliency-based index (VSI). Several prominent
computational VS models have been investigated in the context of IQA and the best
one is chosen for VSI. Extensive experiments performed on four large-scale
benchmark databases demonstrate that the proposed IQA index VSI works better in
terms of the prediction accuracy than all state-of-the-art IQA indices we can
find while maintaining a moderate computational complexity. The MATLAB source
code of VSI and the evaluation results are publicly available online at
http://sse.tongji.edu.cn/linzhang/IQA/VSI/VSI.htm.
PMID- 25122573
TI - Patchwise joint sparse tracking with occlusion detection.
AB - This paper presents a robust tracking approach to handle challenges such as
occlusion and appearance change. Here, the target is partitioned into a number of
patches. Then, the appearance of each patch is modeled using a dictionary
composed of corresponding target patches in previous frames. In each frame, the
target is found among a set of candidates generated by a particle filter, via a
likelihood measure that is shown to be proportional to the sum of patch
reconstruction errors of each candidate. Since the target's appearance often
changes slowly in a video sequence, it is assumed that the target in the current
frame and the best candidates of a small number of previous frames, belong to a
common subspace. This is imposed using joint sparse representation to enforce the
target and previous best candidates to have a common sparsity pattern. Moreover,
an occlusion detection scheme is proposed that uses patch-reconstruction errors
and a prior probability of occlusion, extracted from an adaptive Markov chain, to
calculate the probability of occlusion per patch. In each frame, occluded patches
are excluded when updating the dictionary. Extensive experimental results on
several challenging sequences shows that the proposed method outperforms state-of
the-art trackers.
PMID- 25122574
TI - A universal variational framework for sparsity-based image inpainting.
AB - In this paper, we extend an existing universal variational framework for image
inpainting with new numerical algorithms. Given certain regularization operator
Phi and denoting u the latent image, the basic model is to minimize the l(p),
(p=0,1) norm of Phiu preserving the pixel values outside the inpainting region.
Utilizing the operator splitting technique, the original problem can be
approximated by a new problem with extra variable. With the alternating
minimization method, the new problem can be decomposed as two subproblems with
exact solutions. There are many choices for Phi in our approach such as gradient
operator, wavelet transform, framelet transform, or other tight frames. Moreover,
with slight modification, we can decouple our framework into two relatively
independent parts: 1) denoising and 2) linear combination. Therefore, we can take
any denoising method, including BM3D filter in the denoising step. The numerical
experiments on various image inpainting tasks, such as scratch and text removal,
randomly missing pixel filling, and block completion, clearly demonstrate the
super performance of the proposed methods. Furthermore, the theoretical
convergence of the proposed algorithms is proved.
PMID- 25122575
TI - Design, synthesis, and characterization of 1,3,5-tri(1H-benzo[d]imidazol-2
yl)benzene-based fluorescent supramolecular columnar liquid crystals with a broad
mesomorphic range.
AB - A new kind of supramolecular columnar liquid crystal T-A with a broad mesomorphic
range (up to 164.9 degrees C), good thermal stability, and strong fluorescence
is designed and formed by the H-bonding between 1,3,5-tri(1H-benzo[d]imidazol-2
yl)benzene (T) and serial gallic acid derivatives (A). Two components are easily
available because of simple routes, common reactions, high yields, commercial
starting materials, and inexpensive catalysts. The introduction of the 1,2,3
triazole structure into component A makes the textures different and is slightly
disadvantageous for the T-A complexes.
PMID- 25122576
TI - The changing relationship between bacterial STIs and HIV prevalence in South
Africa - an ecological study.
AB - Prevalence estimates of various bacterial sexually transmitted infections in
South Africa have declined considerably since the mid-1990s. Syphilis among
pregnant women, for example, declined from 10.8% in 1998 to 2.8% in 2001. We used
Pearson's correlation coefficients to estimate the association between the
prevalence of syphilis/male urethral discharge/male genital ulcers and the peak
HIV prevalence at a district and provincial level in the early and late phases of
the HIV epidemic in South Africa. Prevalence estimates of syphilis, male urethral
discharge and male genital ulcers during the period preceding the peak HIV
prevalence were all positively correlated with the peak HIV prevalence at a
provincial level (Pearson's correlation coefficient [r] = 0.83, p = 0.006; r =
0.66, p = 0.052; r = 0.79, 0.011, respectively). These relationships all switched
to a negative association later in the HIV epidemic at a provincial level (r =
0.53, p = 0.14; r = -0.73, p = 0.130; r = -0.54, p = 0.027, respectively). AIDS
mortality may have played an important role in the decline of bacterial sexually
transmitted infections such as syphilis in this region. Consequently, the
relatively recent scale-up of antiretroviral therapy may result in a resurgence
of syphilis and other sexually transmitted infections as observed in high-income
countries.
PMID- 25122577
TI - A case of relapsed visceral Kaposi's sarcoma with bilateral chylothoraces
successfully treated with paclitaxel.
AB - Chylothorax is a rare complication of visceral Kaposi's sarcoma. We report a case
with bilateral chylothoraces secondary to relapsed visceral Kaposi's sarcoma who
was successfully treated with paclitaxel chemotherapy.
PMID- 25122578
TI - Antiretroviral treatment failure predicts mortality in rural Tanzania.
AB - Virological monitoring of HIV-infected patients on antiretroviral treatment (ART)
is rarely available in resource-limited settings and many patients experience
unrecognized virological failure. We studied the long-term consequences of
virological failure in rural Tanzania. Previously, virological efficacy was
measured in a cohort treated with ART. In the present study, patients with
virological failure (VF; HIV-RNA >400 copies/ml) were followed up and compared to
those with virological response (VR; HIV-RNA <400 copies/ml) with regard to
mortality, CD4 change and subsequent virological outcome. Fifty-six patients with
VF had a median CD4 count of 358 cells/ul (interquartile range [IQR] 223-635) and
a median HIV-RNA of 13,573 copies/ml (IQR 2326-129,736). Median CD4 count for
those with VR was 499 cells/ul (IQR 290-636). During a median follow-up time of
39 months (IQR 18-42), 8 of 56 patients (14.3%) with VF died, compared to 1 of 63
patients (1.6%) with VR (p = 0.009). All registered deaths were HIV-related. Of
55 patients with subsequent HIV-RNA measurements, only 12 of 30 (40%) patients
with VF achieved virological suppression, compared to 20 of 25 (80%) patients
with VR (p = 0.003). Virological failure predicted death and subsequent
virological failure in patients on ART in a resource-limited setting.
PMID- 25122579
TI - Measuring patient satisfaction: three years' data and experience of using a
validated patient questionnaire.
AB - A validated patient satisfaction questionnaire for use in sexual health clinics
was run throughout the southwest region (the UK) three times over three years (13
clinics in January 2012 and 12/13 clinics in January 2013 and the same 12 clinics
again in January 2014). The questionnaire covered aspects of pre-appointment,
performance of health care professionals, facilities, privacy, respectful
communication, information on leaving and overall experience. Data from 1750
questionnaires are presented with means and 95% confidence intervals. Patients
under the age of 25 were less likely to rate care as excellent and/or very good
(P = 0.001) compared with those above the age of 25. There was no difference in
satisfaction levels according to gender or sexual orientation. Time in clinic was
strongly associated with satisfaction levels - those in clinic for over 90 min
expressed less satisfaction (P = 0.0005). We hope that other clinics may find it
useful to use the validated questionnaire to look at their own performance and
compare it against the southwest data. The main value is to identify areas where
changes to service delivery could translate into improved practice and improved
satisfaction, particularly where performance is identified as less than the 95%
confidence intervals.
PMID- 25122580
TI - Does dropping day 5 PEP follow-up affect outcomes? An audit of HIV post-exposure
prophylaxis at a central London sexual health clinic.
AB - UK post-exposure prophylaxis (PEP) guidelines were updated by the British
Association for Sexual Health and HIV (BASHH) in 2011. In 2013, we changed policy
to omit day 5 PEP follow-up at 56 Dean Street as it was felt clinically
unnecessary. This audit compares our performance against BASHH standards for PEP
attenders during June 2012 and June 2013. We identified 162 PEP prescriptions;
PEP assessment and appropriate sexually transmitted infection testing was done
well. PEP completion rates and post-PEP HIV testing were lower than BASHH
standards. Following omission of day 5 review, documentation that results have
been checked was poor; however, attendance at follow-up was not adversely
affected.
PMID- 25122582
TI - Covalent linking of quantum dots to polymer for inorganic-inorganic luminescence
films via layer-by-layer assembly with clay.
AB - Herein, positively charged QDs were initially prepared by covalently linking to
poly(allylamine hydrochloride) (PAH). The resulting PAH-modified QDs in
conjunction with MMT nanosheets were utilized to fabricate QDs/MMT UTFs via LBL
assembly. Strong photoluminescence, temperature responsiveness, long-term
stability and high uniformity make these films potential candidates for a wide
range of applications.
PMID- 25122583
TI - Health Characteristics by Geographic Region, large Metropolitan Areas, and Other
Places of Residence, United States - 1969-70.
AB - The estimates for selected health characteristics presented in this report are
based on Health Interview Survey data collected during 1969-70. The health
characteristics discussed include activity limitation due to chronic disease,
disability days, incidence of acute conditions and persons injured,
hospitalization, and physician and dental visits. The information is shown by the
four geographic regions, metropolitan areas, and farm and nonfarm places of
residence outside the metropolitan areas. Another breakdown of the data shows
estimates by residence inside or outside the metropolitan area. An earlier report
(Vital and Health Statistics Series 10, No. 36) contained similar information for
the period July 1963-June 1965.
PMID- 25122581
TI - Social inequalities in early childhood health and development: a European-wide
systematic review.
AB - The evidence examining the relationship between specific social factors and early
childhood health and developmental outcomes has never been systematically
collated or synthesized. This review aims to identify the key social factors
operating at the household, neighborhood, and country levels that drive
inequalities in child health and development. Medline and CHICOS (a European
child-cohort inventory) were systematically searched to identify all European
studies published within the past 10 y. 13,270 Medline articles and 77 European
child cohorts were searched, identifying 201 studies from 32 European countries.
Neighborhood deprivation, lower parental income/wealth, educational attainment,
and occupational social class, higher parental job strain, parental unemployment,
lack of housing tenure, and household material deprivation were identified as the
key social factors associated with a wide range of adverse child health and
developmental outcomes. Similar association trends were observed across most
European countries, with only minor country-level differences. Multiple adverse
social factors operating at both the household and neighborhood levels are
independently associated with a range of adverse health and developmental
outcomes throughout early childhood. The social gradient in health and
developmental outcomes observed throughout the remaining life course may be
partly explained by gradients initiated in early childhood.
PMID- 25122585
TI - Re: "Estimated rate of reactivation of latent tuberculosis infection in the
United States, overall and by population subgroup".
PMID- 25122584
TI - Validity of an ecometric neighborhood physical disorder measure constructed by
virtual street audit.
AB - Neighborhood physical disorder is thought to affect mental and physical health,
but it has been difficult to measure objectively and reliably across large
geographical areas or multiple locales. Virtual street audits are a novel method
for assessing neighborhood characteristics. We evaluated the ecometric properties
of a neighborhood physical disorder measure constructed from virtual street audit
data. Eleven trained auditors assessed 9 previously validated items developed to
capture physical disorder (e.g., litter, graffiti, and abandoned buildings) on
1,826 block faces using Google Street View imagery (Google, Inc., Mountain View,
California) dating from 2007-2011 in 4 US cities (San Jose, California; Detroit,
Michigan; New York, New York; and Philadelphia, Pennsylvania). We constructed a 2
parameter item response theory scale to estimate latent levels of disorder on
each block face and defined a function using kriging to estimate physical
disorder levels, with confidence estimates, for any point in each city. The
internal consistency reliability of the resulting scale was 0.93. The final
measure of disorder was positively correlated with US Census data on unemployment
and housing vacancy and negatively correlated with data on owner-occupied
housing. These results suggest that neighborhood physical disorder can be
measured reliably and validly using virtual audits, facilitating research on
possible associations between physical disorder and health.
PMID- 25122586
TI - High-frequency transcutaneous electrical nerve stimulation alleviates spasticity
after spinal contusion by inhibiting activated microglia in rats.
AB - BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) can be used as a
physical therapy for spasticity, but the effects of TENS on spasticity and its
underlying mechanisms remain unclear. OBJECTIVE: The purpose of this study was to
test the effects of TENS on spasticity and the role of activated microglia as
underlying mechanisms of TENS treatment for spasticity in rats with a 50-mm
contusive spinal cord injury (SCI). METHODS: A spinal contusion was made at the
T12 spinal segment in adult male Sprague-Dawley rats using the NYU impactor.
Behavioral tests for motor function were conducted before and after SCI and
before and after TENS application. To assess spasticity, the modified Ashworth
scale (MAS) was used before and after SCI, high-frequency (HF)/low-frequency (LF)
TENS application at 3 different intensities (motor threshold [MT], 50% and 90%
MT) or minocycline administration. Immunohistochemistry for microglia was
performed at the lumbar spinal segments. RESULTS: Motor recovery reached a
plateau approximately 28 days after SCI. Spasticity was well developed and was
sustained above the MAS grade of 3, beginning at 28 days after SCI. HF-TENS at
90% MT significantly alleviated spasticity. Motor function did not show any
significant changes with LF- or HF-TENS treatment. HF-TENS significantly reduced
the proportion of activated microglia observed after SCI. Minocycline, the
microglia inhibitor, also significantly alleviated spasticity with the reduction
of activated microglia expression. CONCLUSIONS: These results suggest that HF
TENS at 90% MT alleviates spasticity in rats with SCI by inhibiting activated
microglia.
PMID- 25122588
TI - An investigation of heat transfer between a microcantilever and a substrate for
improved thermal topography imaging.
AB - This paper reports the numerical and experimental investigation of heat transfer
from a heated microcantilever to a substrate and uses the resulting insights to
improve thermal topography imaging. The cantilever sensitivity, defined as change
in thermal signal due to changes in the topography height, is relatively constant
for feature heights in the range 100-350 nm. Since the cantilever-substrate heat
transfer is governed by thermal conduction through the air, the cantilever
sensitivity is nearly constant across substrates of varying thermal conductivity.
Surface features with lateral size larger than 2.5 MUm can induce artifacts in
the cantilever signal resulting in measurement errors as large as 28%. These
artifacts arise from thermal conduction from the cantilever in the lateral
direction, parallel to the surface. We show how these artifacts can be removed by
accounting for this lateral conduction and removing it from the thermal signal.
This technique reduces the measurement error by as much as 26%, can be applied to
arbitrary substrate topographies, and can be scaled to arrays of heated
cantilevers. These results could lead to improvements in nanometer-scale thermal
measurements including scanning thermal microscopy and tip-based nanofabrication.
PMID- 25122587
TI - Varied overground walking training versus body-weight-supported treadmill
training in adults within 1 year of stroke: a randomized controlled trial.
AB - BACKGROUND: Although task-related walking training has been recommended after
stroke, the theoretical basis, content, and impact of interventions vary across
the literature. There is a need for a comparison of different approaches to task
related walking training after stroke. OBJECTIVE: To compare the impact of a
motor-learning-science-based overground walking training program with body-weight
supported treadmill training (BWSTT) in ambulatory, community-dwelling adults
within 1 year of stroke onset. METHODS: In this rater-blinded, 1:1 parallel,
randomized controlled trial, participants were stratified by baseline gait speed.
Participants assigned to the Motor Learning Walking Program (MLWP) practiced
various overground walking tasks under the supervision of 1 physiotherapist.
Cognitive effort was encouraged through random practice and limited provision of
feedback and guidance. The BWSTT program emphasized repetition of the normal gait
cycle while supported on a treadmill and assisted by 1 to 3 therapy staff. The
primary outcome was comfortable gait speed at postintervention assessment (T2).
RESULTS: In total, 71 individuals (mean age = 67.3; standard deviation = 11.6
years) with stroke (mean onset = 20.9 [14.1] weeks) were randomized (MLWP, n =
35; BWSTT, n = 36). There was no significant between-group difference in gait
speed at T2 (0.002 m/s; 95% confidence interval [CI] = -0.11, 0.12; P > .05). The
MLWP group improved by 0.14 m/s (95% CI = 0.09, 0.19), and the BWSTT group
improved by 0.14 m/s (95% CI = 0.08, 0.20). CONCLUSIONS: In this sample of
community-dwelling adults within 1 year of stroke, a 15-session program of varied
overground walking-focused training was not superior to a BWSTT program of equal
frequency, duration, and in-session step activity.
PMID- 25122589
TI - In situ assembly of well-dispersed Ni nanoparticles on silica nanotubes and
excellent catalytic activity in 4-nitrophenol reduction.
AB - The easy aggregation nature of ferromagnetic nanoparticles (NPs) prepared by
conventional routes usually leads to a large particle size and low loading, which
greatly limits their applications to the reduction of 4-nitrophenol (4-NP).
Herein, we developed a novel in situ thermal decomposition and reduction strategy
to prepare Ni nanoparticles/silica nanotubes (Ni/SNTs), which can markedly
prevent the aggregation and growth of Ni NPs, resulting in an ultra-small
particle size (about 6 nm), good dispersion and especially high loading of Ni
NPs. It was found that Ni/SNTs, which have a high specific surface area (416 m(2)
g(-1)), exhibit ultra-high catalytic activity in the 4-NP reduction (complete
reduction of 4-NP within only 60 s at room temperature), which is superior to
most noble metal (Au, Pt, and Pd) supported catalysts. Ni/SNTs still showed high
activity even after re-use for several cycles, suggesting good stability. In
particular, the magnetic property of Ni/SNTs makes it easy to recycle for reuse.
PMID- 25122590
TI - Preorganized bis-thioureas as powerful anion carriers: chloride transport by
single molecules in large unilamellar vesicles.
AB - Transmembrane anion carriers (anionophores) have potential in biological research
and medicine, provided high activities can be obtained. There is particular
interest in treating cystic fibrosis (CF), a genetic illness caused by deficient
anion transport. Previous work has found that anionophore designs featuring axial
ureas on steroid and trans-decalin scaffolds can be especially effective. Here we
show that replacement of ureas by thioureas yields substantial further
enhancements. Six new bis-thioureas have been prepared and tested for Cl(-)/NO3(
) exchange in 1-palmitoyl-2-oleoylphosphatidylcholine/cholesterol large
unilamellar vesicles (LUVs). The bis-thioureas are typically >10 times more
effective than the corresponding ureas and are sufficiently active that transport
by molecules acting singly in LUVs is readily detected. The highest activity is
shown by decalin 9, which features N-(3,5-bis(trifluoromethyl)phenyl)thioureido
and octyl ester substituents. A single molecule of transporter 9 in a 200 nm
vesicle promotes Cl(-)/NO3(-) exchange with a half-life of 45 s and an absolute
rate of 850 chloride anions per second. Weight-for-weight, this carrier is only
slightly less effective than CFTR, the natural anion channel associated with CF.
PMID- 25122592
TI - Biomimetic and bioinspired materials for applications in biophotonics.
PMID- 25122591
TI - MR compatibility aspects of a silicon photomultiplier-based PET/RF insert with
integrated digitisation.
AB - The combination of Positron Emission Tomography (PET) and Magnetic Resonance
Imaging (MRI) into a single device is being considered a promising tool for
molecular imaging as it combines the high sensitivity of PET with the functional
and anatomical images of MRI. For highest performance, a scalable, MR compatible
detector architecture with a small form factor is needed, targeting at excellent
PET signal-to-noise ratios and time-of-flight information. Therefore it is
desirable to use silicon photo multipliers and to digitize their signals directly
in the detector modules inside the MRI bore. A preclinical PET/RF insert for
clinical MRI scanner was built to demonstrate a new architecture and to study the
interactions between the two modalities.The disturbance of the MRI's static
magnetic field stays below 2 ppm peak-to-peak within a diameter of 56 mm (90 mm
using standard automatic volume shimming). MRI SNR is decreased by 14%, RF
artefacts (dotted lines) are only visible in sequences with very low SNR.
Ghosting artefacts are visible to the eye in about 26% of the EPI images, severe
ghosting only in 7.6%. Eddy-current related heating effects during long EPI
sequences are noticeable but with low influence of 2% on the coincidences count
rate. The time resolution of 2.5 ns, the energy resolution of 29.7% and the
volumetric spatial resolution of 1.8 mm(3) in the PET isocentre stay unaffected
during MRI operation. Phantom studies show no signs of other artefacts or
distortion in both modalities. A living rat was simultaneously imaged after the
injection with (18)F-Fluorodeoxyglucose (FDG) proving the in vivo capabilities of
the system.
PMID- 25122593
TI - Design and control of a dual unidirectional brake hybrid actuation system for
haptic devices.
AB - Hybrid actuators combining brakes and motors have emerged as an efficient
solution to achieve high performance in haptic devices. In this paper, an
actuation approach using two unidirectional brakes and a DC motor is proposed.
The brakes are coupled to overrunning clutches and can apply a torque in only one
rotational direction. The associated control laws, that are independent of the
virtual environment model, calculate the control gains in real time in order
limit the energy and the stiffness delivered by the motor to ensure stability.
The reference torque is respected using the combination of the motor and the
brake. Finally, an user experiment has been performed to evaluate the influence
of passive and active torque differences in the perception of elasticity. The
proposed actuator has a torque range of 0.03 Nm to 5.5 Nm with a 17.75 kNm (-2)
torque density.
PMID- 25122594
TI - Velocity estimation algorithms for audio-haptic simulations involving stick-slip.
AB - With real-time models of friction that take velocity as input, accuracy depends
in great part on adequately estimating velocity from position measurements. This
process can be sensitive to noise, especially at high sampling rates. In audio
haptic acoustic simulations, often characterized by friction-induced, relaxation
type stick-slip oscillations, this gives a gritty, dry haptic feel and a raspy,
unnatural sound. Numerous techniques have been proposed, but each depend on
tuning parameters so that they may offer a good trade-off between delay and noise
rejection. In an effort to compare fairly, each of thirteen methods considered in
the present study was automatically optimized and evaluated; finally a subset of
these were compared subjectively. Results suggest that no one method is ideal for
all gain levels, though the best general performance was found by using a sliding
mode differentiator as input to a Kalman integrator. An additional conclusion is
that estimators do not approach the quality available in physical velocity
transduction, and therefore such sensors should be considered in haptic device
design.
PMID- 25122595
TI - Pilot study of a new rehabilitation tool: improved unilateral short-term
adaptation of the human angular vestibulo-ocular reflex.
AB - HYPOTHESIS: Unilateral vestibulo-ocular reflex (VOR) short-term adaptation
training causes some increase toward the nonadapting side (~30% of increase on
adapting side). We conducted a pilot study to determine if the increase could be
reduced by providing a visual stimulus during rotations to the nonadapting side.
BACKGROUND: Unilateral vestibular short-term adaptation is a technique that could
increase the ipsilesional VOR response of vestibular patients with unilateral
hypofunction. However, this technique results in the VOR response increasing for
rotations toward the nonadapting (normal) side, which is undesirable because the
VOR will be overcompensatory (causing nonstable vision) during head rotations
toward the normal side. METHODS: We built a portable helmet device that sensed
horizontal angular head velocity to generate a visual target that required a
preset VOR gain (eye velocity/head velocity) for optimal image stabilization that
could be set differently for leftward and rightward head rotations. We tested 10
subjects (six controls and four patients with vestibular hypofunction). We
measured the active and passive VOR gain during high-peak-acceleration,
unilateral, transient head rotations (head impulses) before and after unilateral
VOR adaptation training. RESULTS: In control subjects, for rotations toward the
adapting side (target gain = 1.5), the VOR gain increased because of training by
26.1% +/- 23.4% during active head impulses and by 14.6% +/- 13.0% during passive
head impulses. In contrast, for rotations toward the nonadapting side, there were
no statistically significant increases. CONCLUSION: A visual stimulus driving the
VOR gain to unity toward the nonadapting side aids unilateral adaptation more so
than no visual stimulus.
PMID- 25122596
TI - Dizziness is more prevalent than autophony among patients who have undergone
repair of superior canal dehiscence.
AB - OBJECTIVE: Studies have reported high early success rates in rectifying dizziness
and autophony after primary repair of superior canal dehiscence (SCD). We sought
to identify the prevalence of dizziness and autophony at later time points in
patients who had undergone SCD repair. We also assessed any problems with hearing
in this population, along with prevalence of headaches and decreases in overall
quality of life. STUDY QUALITY DESIGN: Identification of patients via
retrospective chart review, followed by administration of multiple validated
surveys. SETTING: Tertiary, hospital-based neurotology practice. PATIENTS: All 62
patients who had undergone primary SCD repair at Massachusetts Eye and Ear
Infirmary with follow-up time of at least 3 months were contacted, with 38
responses from 22 women and 16 men. The average follow-up was 34 months (range, 3
155 mo). INTERVENTIONS: Patient surveys. MAIN OUTCOME MEASURES: Dizziness
Handicap Inventory and Autophony Index. SECONDARY OUTCOME MEASURES: Hearing
Handicap Survey, MIDAS headache survey, and Short Form-36 Quality of Life Survey.
RESULTS: Twenty patients reported low DHI scores, whereas 18 patients reported
elevated DHI scores corresponding to moderate-to-severe dizziness. Autophony was
less prevalent, as 3 patients experienced autophony in the operated ear, whereas
3 patients experienced "unmasking" of autophony in the contralateral ear. HHI
scores were not significantly different between the low DHI and high DHI group.
There were significantly more female subjects in the high DHI group, which was
also characterized by significantly more severe MIDAS grades and significantly
worse SF-36 scores. CONCLUSION: Dizziness is more prevalent than autophony among
patients who have undergone SCD repair, although the majority of these patients
are satisfied with their decision to undergo surgery. Female sex and migraine
headaches are associated with dizziness in this patient population. Further work
is necessary to determine causal relationships among these associations.
PMID- 25122597
TI - Intratympanic steroid injection for Bell's palsy: preliminary randomized
controlled study.
AB - OBJECTIVE: To investigate adjuvant effect and safety of intratympanic steroid for
the treatment of Bell's palsy. STUDY DESIGN: Prospective, investigator blinded,
randomized study. SETTING: Tertiary referral center. PATIENTS: Patients who
received treatment for Bell's palsy from December 2007 to March 2011 were
randomly divided into two groups. The control group (n = 17) was treated with
systemic steroid plus antiviral agent, and intratympanic steroid injection group
(IT group, n = 14) received intratympanic steroid injection combined with
medications. Facial functions were evaluated on a regular basis up to 6 months.
INTERVENTION: Intratympanic steroid injection. MAIN OUTCOME MEASURES: Facial
nerve functions of initial presentation and follow-up were evaluated with House
Brackmann (H-B) system. Primary outcome was complete recovery rate of 6 months.
Secondary outcomes included improvement of H-B grade within 3 weeks, time of
first improvement in facial function, and cumulative recovery rate. In addition,
subgroup analysis of H-B grade over than IV was performed. RESULTS: Complete
recovery rate was not different between groups. Time of first improvement was
shorter in IT group (p = 0.043). And IT group had a better cumulative recovery
rate (p = 0.041) and showed the significant improvement in H-B grade within 3
weeks compared with control group (p = 0.045). In severe facial palsy, complete
recovery rate of IT group and control group were 80% and 50% (p = 0.16), and IT
groups showed the significant facial improvement within 3 weeks (p = 0.025). And
there were no major adverse effects of intratympanic injection. CONCLUSION:
Intratympanic steroid injection might be a safe and useful adjuvant treatment
modality for Bell's palsy.
PMID- 25122598
TI - Long-term results of 185 consecutive osseointegrated hearing device
implantations: a comparison among children, adults, and elderly.
AB - OBJECTIVE: To determine the occurrence and type of perioperative and
postoperative complications in patients implanted with an osseointegrated hearing
device (OHD) (also known as BAHA/BAHS) and compare results in children, adults,
and elderly and for different surgical techniques. STUDY DESIGN: Retrospective
case file review. SETTING: Tertiary referral center. PATIENTS: Patients implanted
with an OHD between 2004 and 2012, with more than 6 months of follow-up.
INTERVENTION: OHD implantation. MAIN OUTCOME MEASURES: Implant loss, adverse skin
reactions (Holgers' score, >=2), skin overgrowth, and discomfort resulting in
abutment and/or implant removal. RESULTS: One hundred eighty-five implantations
in 176 patients were reviewed. Overall, 3.8% of the implants were lost
spontaneously after a mean of 2.5 years. Implant loss in children was 18% versus
2.5% in adults and 3.8% in elderly. Adverse skin reactions occurred in 14% of
observations overall; in 10% in children compared with 16% in adults and 9% in
elderly. Partial or total skin overgrowth was seen in 4% and 6% of the
observations in children and adults, respectively, whereas none of the elderly
experienced this problem. The abutment was removed because of discomfort and/or
no benefit in 10% overall, in 13% of adults, and in 6% of the elderly; none of
the children opted for removal. Linear incision technique showed fewest
complications. CONCLUSION: OHD implantation is a procedure with few major
complications. Adverse skin reaction is the most common complication. Children
lose the implant more frequently than adults. Elderly patients have less adverse
skin reactions/skin overgrowth. Discomfort leading to abutment removal is a
concern especially among adults.
PMID- 25122599
TI - Calvarium thinning in patients with spontaneous cerebrospinal fluid leak.
AB - OBJECTIVE: To determine the thickness of the calvarium in patients with
spontaneous cerebrospinal fluid (CSF) leaks. STUDY DESIGN: Case control study.
SETTING: University of Iowa Hospitals and Clinics. PATIENTS: Those with a
confirmed spontaneous CSF leak compared to non-obese (body mass index, BMI < 30)
and obese (BMI >= 30) cochlear implant (CI) control groups. All patients had to
have temporal bone CT scans that fit specified criteria. INTERVENTION: Bilateral
volumetric analysis of the squamous temporal bone and the zygoma in all patients.
Assessment of patient age, sex, BMI, and medical comorbidities. MAIN OUTCOME
MEASURE: Assessment of the average thickness of the squamous temporal bone and
zygoma compared to control groups. RESULTS: The average BMI of patients with
spontaneous CSF leaks was significantly higher than non-obese CI controls (43.73
+/- 9.19 vs. 24.60 +/- 3.10; P < 0.0001). The calvarium in patients with
spontaneous CSF leaks was 23% thinner than both non-obese CI controls (3.29 +/-
0.68 vs. 4.25 +/- 0.58; P < 0.0001) and obese CI controls (3.29 +/- 0.68 vs. 4.27
+/- 0.68; P < 0.0001). In addition, the skull thickness of obese CI patients
(body mass index, BMI = 37.34 +/- 6.1) was not significantly different from non
obese CI controls (4.27 +/- 0.68 vs. 4.25 +/- 0.58; P = 0.92). The extracranial
zygoma was not significantly different among the three groups (ANOVA = 0.9). In
our study groups, 5.8% of both CI control groups had the diagnosis of obstructive
sleep apnea (OSA), whereas 46.2% of the spontaneous CSF leak patients presented
with the diagnosis of OSA. CONCLUSION: Patients with spontaneous CSF leak are
more likely to be obese, have the diagnosis of OSA, and show thinning of their
entire calvarium that is independent of BMI. These data suggest an additional
obesity-associated intracranial process contributes to skull thinning.
PMID- 25122601
TI - Influence of cochlear implant insertion depth on performance: a prospective
randomized trial.
AB - OBJECTIVE: The purpose of the present study was to assess the influence of
electrode insertion length on cochlear implant (CI) performance. STUDY DESIGN:
Prospective randomized allocation of CI patients to receive either a standard
(26.4 mm)- or medium (20.9 mm)-length electrode array. The processing strategy
and electrode insertion number were held constant. The postoperative testing
audiologist was blinded to the map details and array. SETTING: Tertiary referral
center. PATIENTS: Thirteen adult CI candidates randomized to receive the standard
(n = 7) or medium-length (n = 6) electrode array. INTERVENTION(S): Unilateral CI
using standard- or medium-length array from the same implant system. MAIN OUTCOME
MEASURES(S): Speech perception was assessed with HINT sentences in quiet and
steady-state noise (SNR, +10) and CNC words in quiet at defined intervals.
Quality of life was assessed using the Hearing Device Satisfaction Survey and the
Abbreviated Profile of Hearing Aid Benefit (APHAB). Music perception was assessed
using the Musical Sounds In Cochlear implants (MuSIC) test. Postoperative
electrode insertion angle was assessed using reconstructed computed tomographic
images. RESULTS: Interim analysis necessitated discontinuation of subject
enrollment by the institutional review board. There was a trend (p = 0.07) for
improved speech perception performance among standard array patients. This
difference was significant when the standard array group was increased
retrospectively. Quality of life and music perception differences were not
apparent between groups. CONCLUSION: Longer electrode insertions (and greater
insertion angles) appear to offer better speech perception performance in the
early postactivation period when using the same implant system.
PMID- 25122600
TI - Intracochlear inflammatory response to cochlear implant electrodes in humans.
AB - HYPOTHESIS: This study evaluates the types and degrees of tissue response
adjacent to the electrode of multichannel cochlear implants. BACKGROUND: Cochlear
implant electrodes have been classified as biocompatible prostheses.
Nevertheless, in some reports, electrode extrusion, chronic inflammation, and
even soft failure of the implant system have been attributed to a tissue response
to the electrode. METHODS: All celloidin-embedded temporal bones with
multichannel cochlear implants from the temporal bone collection of the
Massachusetts Eye and Ear Infirmary were included in the study. A total of 28
temporal bones from 21 subjects were identified and processed for histology. The
severity of cellular response including eosinophil and lymphocytic infiltration,
giant cell reaction, new bone formation, and fibrosis were scored on a scale from
0 to 3 at three 1-mm segments along the electrode: first 1 mm at the
cochleostomy, last 1 mm from the tip of the electrode, and midway between these
proximal and distal segments. The values were compared using the Wilcoxon test.
RESULTS: A granulomatous reaction to the electrode was observed in 27 (96.4%)
temporal bones. Eosinophil infiltration was observed in 7 (25%) temporal bones,
suggesting an allergic reaction. The Inflammatory response to the electrode was
significantly greater at the basal turn of cochlea close to the cochleostomy (p <
0.05) than distal to it. CONCLUSION: An inflammatory response is common after
cochlear implantation, and it is more robust at the cochleostomy than distal to
it, suggesting the role of trauma of insertion as a contributing factor.
PMID- 25122602
TI - Radiologic classification of superior canal dehiscence: implications for surgical
repair.
AB - OBJECTIVE: Surgical access to repair a superior canal dehiscence (SCD) is
influenced by the location of the bony defect and its relationship to surrounding
tegmen topography as seen on computed tomography. There are currently no agreed
upon methods of characterizing these radiologic findings. We propose a formal
radiologic classification system of SCD based on dehiscence location and adjacent
tegmen topography. STUDY DESIGN: Retrospective case review SETTING: Tertiary,
neurotology referral center PATIENTS: We identified 298 patients with superior
canal dehiscence on CT from February 2001 to October 2013. Of these, 251 had
symptomatic superior canal dehiscence syndrome and were included in the study.
INTERVENTION: Patients underwent high-resolution temporal bone CT scans with
creation of axial, coronal, Poschl, and Stenver reformatted images to examine the
superior semicircular canal. Two residents-in-training and a head and neck
radiologist independently read the scans. MAIN OUTCOME MEASURES: CT scans were
assessed for (1) superior canal dehiscence or "near" dehiscence, (2) defect
location relative to the skull base, (3) surrounding tegmen defects, (4)
geniculate ganglion dehiscence, (5) superior petrosal sinus-associated dehiscence
(SPS), (6) low-lying tegmen, and (7) the distance between the outer table of the
temporal bone and the arcuate eminence.
PMID- 25122603
TI - A Neurodynamic Optimization Method for Recovery of Compressive Sensed Signals
With Globally Converged Solution Approximating to l0 Minimization.
AB - Finding the optimal solution to the constrained l0 -norm minimization problems in
the recovery of compressive sensed signals is an NP-hard problem and it usually
requires intractable combinatorial searching operations for getting the global
optimal solution, unless using other objective functions (e.g., the l1 norm or lp
norm) for approximate solutions or using greedy search methods for locally
optimal solutions (e.g., the orthogonal matching pursuit type algorithms). In
this paper, a neurodynamic optimization method is proposed to solve the l0 -norm
minimization problems for obtaining the global optimum using a recurrent neural
network (RNN) model. For the RNN model, a group of modified Gaussian functions
are constructed and their sum is taken as the objective function for
approximating the l0 norm and for optimization. The constructed objective
function sets up a convexity condition under which the neurodynamic system is
guaranteed to obtain the globally convergent optimal solution. An adaptive
adjustment scheme is developed for improving the performance of the optimization
algorithm further. Extensive experiments are conducted to test the proposed
approach in this paper and the output results validate the effectiveness of the
new method.
PMID- 25122604
TI - Identifying Similar Cases in Document Networks Using Cross-Reference Structures.
AB - Our objective was to explore the creation of document networks based on different
thresholds of shared information and different clustering algorithms on those
networks to identify document clusters describing similar clinical cases. We
created networks from vaccine adverse event report sets using seven approaches
for linking reports. We then applied three clustering algorithms [visualization
of similarities (VOS), Louvain, k-means] to these networks and evaluated their
ability to identify known clusters. The report sets included one simulated set
and three sets from the Vaccine Adverse Event Reporting System; each was split
into training and testing subsets. Training subsets were used to estimate
parameter values for the clustering algorithms and testing subsets to evaluate
clusters. We created the networks by linking reports based on shared information
in the form either of individual Medical Dictionary for Regulatory Activities
Preferred Terms (PTs) or of dyads, triplets, quadruplets, quintuplets, and
sextuplets of PTs; we created another network by weighting the single PT network
connections by Lin's information theoretic approach to similarity. We then
repeated this entire process using networks based on text mining output rather
than structured data. We evaluated report clustering using recall, precision, and
f-measure. The VOS algorithm outperformed Louvain and k-means in general. The
best weighting scheme appeared to be related to the complexity of the known
cluster. For example, singleton weighting performed best for an intussusception
cluster driven by a single PT. We observed marginal differences between the code-
and textual-based clustering. In conclusion, our approach supported
identification of similar nodes in a document network.
PMID- 25122605
TI - Accurate segmentation of partially overlapping cervical cells based on dynamic
sparse contour searching and GVF snake model.
AB - Overlapping cells segmentation is one of the challenging topics in medical image
processing. In this paper, we propose to approximately represent the cell contour
as a set of sparse contour points, which can be further partitioned into two
parts: the strong contour points and the weak contour points. We consider the
cell contour extraction as a contour points locating problem and propose an
effective and robust framework for segmentation of partially overlapping cells in
cervical smear images. First, the cell nucleus and the background are extracted
by a morphological filtering-based K-means clustering algorithm. Second, a
gradient decomposition-based edge enhancement method is developed for enhancing
the true edges belonging to the center cell. Then, a dynamic sparse contour
searching algorithm is proposed to gradually locate the weak contour points in
the cell overlapping regions based on the strong contour points. This algorithm
involves the least squares estimation and a dynamic searching principle, and is
thus effective to cope with the cell overlapping problem. Using the located
contour points, the Gradient Vector Flow Snake model is finally employed to
extract the accurate cell contour. Experiments have been performed on two
cervical smear image datasets containing both single cells and partially
overlapping cells. The high accuracy of the cell contour extraction result
validates the effectiveness of the proposed method.
PMID- 25122606
TI - EEG compression of scalp recordings based on dipole fitting.
AB - A novel technique for electroencephalogram (EEG) compression is proposed in this
paper. This technique models the intrinsic dependence inherent between the
different EEG channels. It is based on methods borrowed from dipole fitting that
is usually used in order to find a solution to the classic problems in EEG
analysis: inverse and forward problems. To compress the EEG signals, the forward
model based on approximated source dipoles is first used to provide an
approximation of the recorded signals. Then, (based on a smoothness factor)
appropriate coding techniques are suggested to compress the residuals of the
fitting process. Results show that this technique works well for different
recordings and for different patients, and is even able to provide near-lossless
compression for certain types of recordings.
PMID- 25122607
TI - Geometric asymmetry driven Janus micromotors.
AB - The production and application of nano-/micromotors is of great importance. In
order for the motors to work, asymmetry in their chemical composition or physical
geometry must be present if no external asymmetric field is applied. In this
paper, we present a "coconut" micromotor made of platinum through the partial or
complete etching of the silica templates. It was shown that although both the
inner and outer surfaces are made of the same material (Pt), motion of the
structure can be observed as the convex surface is capable of generating oxygen
bubbles. This finding shows that not only the chemical asymmetry of the
micromotor, but also its geometric asymmetry can lead to fast propulsion of the
motor. Moreover, a considerably higher velocity can be seen for partially etched
coconut structures than the velocities of Janus or fully etched, shell-like
motors. These findings will have great importance on the design of future
micromotors.
PMID- 25122611
TI - Sensorimotor adaptation: multiple forms of plasticity in motor circuits.
AB - One of the most striking properties of the adult central nervous system is its
ability to undergo changes in function and/or structure. In mammals, learning is
a major inducer of adaptive plasticity. Sensorimotor adaptation is a type of
procedural--motor--learning that allows maintaining accurate movements in the
presence of environmental or internal perturbations by adjusting motor output. In
this work, we will review experimental evidence gathered from rodents and human
and nonhuman primates pointing to possible sites of adaptation-related plasticity
at different levels of organization of the nervous system.
PMID- 25122609
TI - Inhibition of sphingosine kinase 2 downregulates the expression of c-Myc and Mcl
1 and induces apoptosis in multiple myeloma.
AB - Sphingolipid metabolism is being increasingly recognized as a key pathway in
regulating cancer cell survival and proliferation. However, very little is known
about its role in multiple myeloma (MM). We investigated the potential of
targeting sphingosine kinase 2 (SK2) for the treatment of MM. We found that SK2
was overexpressed in MM cell lines and in primary human bone marrow (BM) CD1381
myeloma cells. Inhibition of SK2 by SK2- specific short hairpin RNA or ABC294640
(a SK2 specific inhibitor) effectively inhibited myeloma cell proliferation and
induced caspase 3-mediated apoptosis. ABC294640 inhibited primary human CD1381
myeloma cells with the same efficacy as with MM cell lines. ABC294640 effectively
induced apoptosis of myeloma cells, even in the presence of BM stromal cells.
Furthermore, we found that ABC294640 downregulated the expression of pS6 and
directed c-Myc and myeloid cell leukemia 1 (Mcl-1) for proteasome degradation. In
addition, ABC294640 increased Noxa gene transcription and protein expression.
ABC294640, per se, did not affect the expression of B-cell lymphoma 2 (Bcl-2),
but acted synergistically with ABT-737 (a Bcl-2 inhibitor) in inducing myeloma
cell death. ABC294640 suppressed myeloma tumor growth in vivo in mouse myeloma
xenograft models. Our data demonstrated that SK2 provides a novel therapeutic
target for the treatment of MM.This trial was registered at
www.clinicaltrials.gov as #NCT01410981.
PMID- 25122610
TI - Functional characterization of the human dendritic cell immunodeficiency
associated with the IRF8(K108E) mutation.
AB - We have previously reported on a unique patient in whom homozygosity for a
mutation at IRF8 (IRF8(K108E)) causes a severe immunodeficiency. Laboratory
evaluation revealed a highly unusual myeloid compartment, remarkable for the
complete absence of CD141 and CD161 monocytes, absence of CD11c1 conventional
dendritic cells (DCs) and CD11c1/CD1231 plasmacytoid DCs, and striking
granulocytic hyperplasia. The patient initially presented with severe
disseminated mycobacterial and mucocutaneous fungal infections and was ultimately
cured by cord blood transplant. Sequencing RNA from the IRF8(K108E) patient's
primary blood cells prior to transplant shows not only depletion of IRF8-bound
and IRF8-regulated transcriptional targets, in keeping with the distorted
composition of the myeloid compartment, but also a paucity of transcripts
associated with activated CD41 and CD81 T lymphocytes. This suggests that T cells
reared in the absence of a functional antigen-presenting compartment in
IRF8(K108E) are anergic. Biochemical characterization of the IRF8(K108E) mutant
in vitro shows that loss of the positively charged side chain at K108 causes loss
of nuclear localization and loss of transcriptional activity, which is
concomitant with decreased protein stability, increased ubiquitination, increased
small ubiquitin-like modification, and enhanced proteasomal degradation. These
findings provide functional insight into the molecular basis of immunodeficiency
associated with loss of IRF8.
PMID- 25122614
TI - Sulfitobacter geojensis sp. nov., Sulfitobacter noctilucae sp. nov., and
Sulfitobacter noctilucicola sp. nov., isolated from coastal seawater.
AB - Four Gram-stain-negative, aerobic, rod-shaped bacterial strains, MM-124, MM-126,
NB-68 and NB-77, were isolated from the coastal seawater or a region with a bloom
of sea sparkle around Geoje island in Korea. The sequence similarity values of
the 16S rRNA gene between the isolates and Sulfitobacter mediterraneus DSM
12244(T) ranged from 97.7 to 98.2%, and phylogenetic relationships suggested that
they belong to a phylogenetic branch that includes the genera Sulfitobacter and
Roseobacter. The isoprenoid quinone of all three novel strains was ubiquinone-10
and the major fatty acid was cis-vaccenic acid, as in other species of the genus
Sulfitobacter. However, there were several differences in the morphological,
physiological and biochemical characteristics among the four strains and the
reference species of the genus Sulfitobacter. Moreover, the average nucleotide
identity values between the three sequenced isolates and the reference strains
were below 76.33, indicating that genomic variation exists between the isolates
and reference strains. Chemotaxonomic characteristics together with phylogenetic
affiliations and genomic distances illustrate that strains MM-124, NB-68 and NB
77 represent novel species of the genus Sulfitobacter, for which the names
Sulfitobacter geojensis sp. nov. (type strain MM-124(T) =KCTC 32124(T) =JCM
18835(T)), Sulfitobacter noctilucae sp. nov. (type strain NB-68(T) =KCTC 32122(T)
=JCM 18833(T)) and Sulfitobacter noctilucicola sp. nov. (type strain NB-77(T)
=KCTC 32123(T) =JCM 18834(T)) are proposed.
PMID- 25122612
TI - Unbiased analysis of potential targets of breast cancer susceptibility loci by
Capture Hi-C.
AB - Genome-wide association studies have identified more than 70 common variants that
are associated with breast cancer risk. Most of these variants map to non-protein
coding regions and several map to gene deserts, regions of several hundred
kilobases lacking protein-coding genes. We hypothesized that gene deserts harbor
long-range regulatory elements that can physically interact with target genes to
influence their expression. To test this, we developed Capture Hi-C (CHi-C),
which, by incorporating a sequence capture step into a Hi-C protocol, allows high
resolution analysis of targeted regions of the genome. We used CHi-C to
investigate long-range interactions at three breast cancer gene deserts mapping
to 2q35, 8q24.21, and 9q31.2. We identified interaction peaks between putative
regulatory elements ("bait fragments") within the captured regions and "targets"
that included both protein-coding genes and long noncoding (lnc) RNAs over
distances of 6.6 kb to 2.6 Mb. Target protein-coding genes were IGFBP5, KLF4,
NSMCE2, and MYC; and target lncRNAs included DIRC3, PVT1, and CCDC26. For one
gene desert, we were able to define two SNPs (rs12613955 and rs4442975) that were
highly correlated with the published risk variant and that mapped within the bait
end of an interaction peak. In vivo ChIP-qPCR data show that one of these,
rs4442975, affects the binding of FOXA1 and implicate this SNP as a putative
functional variant.
PMID- 25122613
TI - High-resolution mapping of transcriptional dynamics across tissue development
reveals a stable mRNA-tRNA interface.
AB - The genetic code is an abstraction of how mRNA codons and tRNA anticodons
molecularly interact during protein synthesis; the stability and regulation of
this interaction remains largely unexplored. Here, we characterized the
expression of mRNA and tRNA genes quantitatively at multiple time points in two
developing mouse tissues. We discovered that mRNA codon pools are highly stable
over development and simply reflect the genomic background; in contrast, precise
regulation of tRNA gene families is required to create the corresponding tRNA
transcriptomes. The dynamic regulation of tRNA genes during development is
controlled in order to generate an anticodon pool that closely corresponds to
messenger RNAs. Thus, across development, the pools of mRNA codons and tRNA
anticodons are invariant and highly correlated, revealing a stable molecular
interaction interlocking transcription and translation.
PMID- 25122615
TI - Zhongshania aliphaticivorans sp. nov., an aliphatic hydrocarbon-degrading
bacterium isolated from marine sediment, and transfer of Spongiibacter borealis
Jang et al. 2011 to the genus Zhongshania as Zhongshania borealis comb. nov.
AB - A Gram-staining-negative, facultatively aerobic bacterium, designated SM-2(T),
was isolated from a sea-tidal flat of Yellow Sea, South Korea. Cells were
catalase- and oxidase-positive motile rods with a single polar flagellum. Growth
of strain SM-2(T) was observed at 10-37 degrees C (optimum, 25-30 degrees C),
at pH 5.5-8.5 (optimum, pH 7.0-7.5) and in the presence of 0-11% (w/v) NaCl
(optimum, 2%). Strain SM-2(T) contained ubiquinone-8 (Q-8) as the sole isoprenoid
quinone and C(17:1)omega8c, summed feature 3 (comprising C(16:1)omega7c and/or
iso-C(15:0) 2-OH), C(17:0) and C(18:1)omega7c as the major fatty acids.
Phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and an
unidentified lipid were identified as the major cellular polar lipids. The G+C
content of the genomic DNA was 52.2 mol%. Phylogenetic analysis based on 16S rRNA
gene sequences showed that strain SM-2(T) formed a tight phyletic lineage with
Zhongshania antarctica ZS5-23(T), Zhongshania guokunii ZS6-22(T) and
Spongiibacter borealis CL-AS9(T), but that S. borealis CL-AS9(T) was distinct
from other species of the genus Spongiibacter. Based on 16S rRNA gene sequence
similarities, strain SM-2(T) was most closely related to S. borealis CL-AS9(T),
Z. antarctica ZS5-23(T) and Z. guokunii ZS6-22(T), with similarities of 99.5%,
98.9% and 98.7%, respectively, but the DNA-DNA hybridization values among these
species were clearly lower than 70%. On the basis of chemotaxonomic data and
molecular properties, we propose strain SM-2(T) represents a novel species of the
genus Zhongshania with the name Zhongshania aliphaticivorans sp. nov. (type
strain SM-2(T) =KACC 18120(T) =JCM 30138(T)). We also propose the transfer of
Spongiibacter borealis Jang et al. 2011 to the genus Zhongshania as Zhongshania
borealis comb. nov. (type strain CL-AS9(T) =KCCM 90094(T) =JCM 17304(T)).
PMID- 25122617
TI - Determining the reach of a home-based physical activity program for older adults
within the context of a randomized controlled trial.
AB - Determining the reach of physical activity (PA) programs is challenging due to
inconsistent reporting across studies. The purpose of this study was to document
multiple indicators of program reach for a 6-month, Digital Versatile Disc (DVD)
delivered home-based PA program. Radio, newspaper and direct mailing
advertisements were tracked to determine costs as well as the number and
representativeness of older adults exposed and responding to recruitment. It was
estimated that all older adults in the recruitment area (n = 105 515) may have
been exposed to at least one of the recruitment strategies--563 responded and 383
were screened as eligible. Of those that enrolled (n = 307), the DVD reached
between 81% and 97% of the participants over each month within the 6 month
period. Newspaper advertisements were most effective (n = 222) at a cost of $78
per participant enrolled. CONCLUSION: Using multiple indicators of reach supports
the accurate calculation and generalizability of recruiting older adults into PA
programs.
PMID- 25122618
TI - Male smoker and non-smoker responses to television advertisements on the harms of
secondhand smoke in China, India and Russia.
AB - Mass media campaigns can play an important role in strengthening support for
smoke-free policies and reducing exposure to secondhand smoke (SHS). Identifying
anti-SHS advertisements that are effective in diverse cultural contexts may allow
for resource sharing in low- and middle-income countries. A convenience sample of
481 male cigarette smokers and non-smokers in three high tobacco burden and
culturally dissimilar countries (India, China and Russia) viewed and rated five
anti-SHS ads. Multivariate logistic regression analyses were conducted for
'Message Acceptance', 'Negative Emotion', 'Perceived Effectiveness' and
'Behavioral Intentions'. Smokers and non-smokers in all countries consistently
rated the strong graphic, health harm ads as the most effective, and the
'informational' ad as the least effective overall: the graphic ad 'Baby Alive'
was at least 1.8 times more likely than the informational ad 'Smoke-free works'
to receive positive ratings on all four outcomes (all P < 0.001). Graphic, health
harm messages about SHS exposure have the greatest universal appeal and are the
most effective in motivating changes in behavioral intentions. Similarity in
reactions between smokers and non-smokers, and across countries, suggests that
resource sharing and the use of a single graphic ad targeted at smokers and non
smokers would be cost-efficient strategies.
PMID- 25122616
TI - Feasibility and reliability of pocket-size ultrasound examinations of the pleural
cavities and vena cava inferior performed by nurses in an outpatient heart
failure clinic.
AB - BACKGROUND: Routine assessment of volume state by ultrasound may improve follow
up of heart failure patients. AIMS: We aimed to study the feasibility and
reliability of focused pocket-size ultrasound examinations of the pleural
cavities and the inferior vena cava performed by nurses to assess volume state at
an outpatient heart failure clinic. METHODS: Ultrasound examinations were
performed in 62 included heart failure patients by specialized nurses with a
pocket-size imaging device (PSID). Patients were then re-examined by a
cardiologist with a high-end scanner for reference within 1 h. Specialized nurses
were able to obtain and interpret images from both pleural cavities and the
inferior vena cava and estimate the volume status in all patients. RESULTS: Time
consumption for focused ultrasound examination was median 5 min. In total 26
patients had any kind of pleural effusion (in 39 pleural cavities) by reference.
The sensitivity, specificity, positive and negative predictive values were high,
all >= 92%. The correlations with reference were high for all measurements, all r
>= 0.79. Coefficients of variation for end-expiratory dimension of inferior vena
cava and quantification of pleural effusion were 10.8% and 12.7%, respectively.
CONCLUSIONS: Specialized nurses were, after a dedicated training protocol, able
to obtain reliable recordings of both pleural cavities and the inferior vena cava
by PSID and interpret the images in a reliable way. Implementing focused
ultrasound examinations to assess volume status by nurses in an outpatient heart
failure clinic may improve diagnostics, and thus improve therapy.
PMID- 25122619
TI - Understanding something that is remotely sensible, scaling active chlorophyll
fluorescence from leaves to canopies at ranges of ~50 metres.
PMID- 25122620
TI - Seasonal changes in carbon and nitrogen compound concentrations in a Quercus
petraea chronosequence.
AB - Forest productivity declines with tree age. This decline may be due to changes in
metabolic functions, resource availability and/or changes in resource allocation
(between growth, reproduction and storage) with tree age. Carbon and nitrogen
remobilization/storage processes are key to tree growth and survival. However,
studies of the effects of tree age on these processes are scarce and have not yet
considered seasonal carbon and nitrogen variations in situ. This study was
carried out in a chronosequence of sessile oak (Quercus petraea Liebl.) for 1
year to survey the effects of tree age on the seasonal changes of carbon and
nitrogen compounds in several tree compartments, focusing on key phenological
stages. Our results highlight a general pattern of carbon and nitrogen function
at all tree ages, with carbon reserve remobilization at budburst for growth,
followed by carbon reserve formation during the leafy season and carbon reserve
use during winter for maintenance. The variation in concentrations of nitrogen
compounds shows less amplitude than that of carbon compounds. Storage as proteins
occurs later, and mainly depends on leaf nitrogen remobilization and root uptake
in autumn. We highlight several differences between tree age groups, in
particular the loss of carbon storage function of fine and medium-sized roots
with tree ageing. Moreover, the pattern of carbon compound accumulation in
branches supports the hypothesis of a preferential allocation of carbon towards
growth until the end of wood formation in juvenile trees, at the expense of the
replenishment of carbon stores, while mature trees start allocating carbon to
storage right after budburst. Our results demonstrate that at key phenological
stages, physiological and developmental functions differ with tree age, and
together with environmental conditions, influence the carbon and nitrogen
concentration variations in sessile oaks.
PMID- 25122621
TI - CecropinXJ, a silkworm antimicrobial peptide, induces cytoskeleton disruption in
esophageal carcinoma cells.
AB - Antimicrobial peptides exist in the non-specific immune system of organism and
participate in the innate host defense of each species. CecropinXJ, a cationic
antimicrobial peptide, possesses potent anticancer activity and acts
preferentially on cancer cells instead of normal cells, but the mechanism of
cancer cell death induced by cecropinXJ remains largely unknown. This study was
performed to investigate the cytoskeleton-disrupting effects of cecropinXJ on
human esophageal carcinoma cell line Eca109 using scanning electron microscopy
observation, fluorescence imaging, cell migration and invasion assays, western
blotting, and quantitative reverse transcription polymerase chain reaction (qRT
PCR) analysis. The electronic microscope and fluorescence imaging observation
suggested that cecropinXJ could result in morphological changes and induce damage
to microtubules and actin of Eca109 cells in a dose-dependent manner. The cell
migration and invasion assays demonstrated that cecropinXJ could inhibit
migration and invasion of tumor cells. Western blot and qRT-PCR analysis showed
that there was obvious correlation between microtubule depolymerization and actin
polymerization induced by cecropinXJ. Moreover, cecropinXJ might also cause
decreased expression of alpha-actin, beta-actin, gamma-actin, alpha-tubulin, and
beta-tubulin genes in concentration- and time-dependent manners. In summary, this
study indicates that cecropinXJ triggers cytotoxicity in Eca109 cells through
inducing the cytoskeleton destruction and regulating the expression of
cytoskeleton proteins. This cecropinXJ-mediated cytoskeleton-destruction effect
is instrumental in our understanding of the detailed action of antimicrobial
peptides in human cancer cells and cecropinXJ might be a potential therapeutic
agent for the treatment of cancer in the future.
PMID- 25122622
TI - Beam-induced motion correction for sub-megadalton cryo-EM particles.
AB - In electron cryo-microscopy (cryo-EM), the electron beam that is used for imaging
also causes the sample to move. This motion blurs the images and limits the
resolution attainable by single-particle analysis. In a previous Research article
(Bai et al., 2013) we showed that correcting for this motion by processing movies
from fast direct-electron detectors allowed structure determination to near
atomic resolution from 35,000 ribosome particles. In this Research advance
article, we show that an improved movie processing algorithm is applicable to a
much wider range of specimens. The new algorithm estimates straight movement
tracks by considering multiple particles that are close to each other in the
field of view, and models the fall-off of high-resolution information content by
radiation damage in a dose-dependent manner. Application of the new algorithm to
four data sets illustrates its potential for significantly improving cryo-EM
structures, even for particles that are smaller than 200 kDa.
PMID- 25122623
TI - Cryo-EM enters a new era.
AB - Advances in detector hardware and image-processing software have led to a
revolution in the use of electron cryo-microscopy to determine complex molecular
structures at high resolution.
PMID- 25122625
TI - Advancing research.
AB - eLife has introduced a new type of article-the Research Advance-that allows the
authors of an eLife paper to publish results that build on their original
research paper.
PMID- 25122626
TI - Strategies to Promote Cultural Competence in Distance Education.
AB - Cultural competence is a mainstay in health care and nursing education. With the
expansion in the number of distance-based nursing programs across the country,
innovative teaching methods for distance learning faculty are required to instill
cultural competence in students. Faculty must be deliberate when planning
distance-based learning activities that incorporate cultural experiences. This
article describes several such strategies including the creative use of blogging,
recorded lectures, the online synchronous classroom, social media, and cultural
immersion projects. These methods capitalize on existing information technologies
and offer distance-based students the opportunity to connect with one another, as
well as develop the awareness, sensitivity, and respect that is required when
providing culturally competent care. These teaching methods are modifiable to
meet the teaching and learning needs of the faculty and the students, thereby
allowing educators to support the integration of cultural competence into patient
care for distance students.
PMID- 25122624
TI - Complexin inhibits spontaneous release and synchronizes Ca2+-triggered synaptic
vesicle fusion by distinct mechanisms.
AB - Previously we showed that fast Ca(2+)-triggered vesicle fusion with reconstituted
neuronal SNAREs and synaptotagmin-1 begins from an initial hemifusion-free
membrane point contact, rather than a hemifusion diaphragm, using a single
vesicle-vesicle lipid/content mixing assay (Diao et al., 2012). When complexin-1
was included, a more pronounced Ca(2+)-triggered fusion burst was observed,
effectively synchronizing the process. Here we show that complexin-1 also reduces
spontaneous fusion in the same assay. Moreover, distinct effects of several
complexin-1 truncation mutants on spontaneous and Ca(2+)-triggered fusion closely
mimic those observed in neuronal cultures. The very N-terminal domain is
essential for synchronization of Ca(2+)-triggered fusion, but not for suppression
of spontaneous fusion, whereas the opposite is true for the C-terminal domain. By
systematically varying the complexin-1 concentration, we observed differences in
titration behavior for spontaneous and Ca(2+)-triggered fusion. Taken together,
complexin-1 utilizes distinct mechanisms for synchronization of Ca(2+)-triggered
fusion and inhibition of spontaneous fusion.
PMID- 25122627
TI - Managing the ethical challenges of next-generation sequencing in genomic
medicine.
AB - INTRODUCTION: Next-generation sequencing (NGS) is transforming the conduct of
genetic research and diagnostic investigation. This creates new challenges as it
generates additional information, including unsought and unwanted information.
Nevertheless, this information must be deliberately managed-interpreted,
disclosed and then either stored or destroyed. AREAS OF AGREEMENT: Handling the
process of consent to exome or genome sequencing should include discussion about
the possible detection of variants of uncertain significance (VUSs) or incidental
findings (IFs) that the patient may prefer not to hear about. A plan should be
drawn up that specifies whether and how the patient would be recontacted in the
future with new interpretations. AREAS OF CONTROVERSY: There is an active debate
about which IFs or VUSs should be disclosed to the patient when an exome or
genome sequence has been performed, or whether all findings of any possible
relevance should always be disclosed. How this is managed has important
implications for the initial explanation of the test to the patient and the
process of consent. The assumption is often made that all sequence information
should be stored, but this may not be sustainable or useful. GROWING POINTS:
Efforts are being made to build a consensus on what 'incidental' information
should be disclosed. These policy questions are being addressed in many centres
and practices are evolving rapidly. AREAS TIMELY FOR DEVELOPING RESEARCH: Those
interested in genetics, public health, bioethics and medical ethics may wish to
debate these issues and influence future practice in both genetic research and
genetic diagnostic services.
PMID- 25122628
TI - Bed rest promotes reductions in walking speed, functional parameters, and aerobic
fitness in older, healthy adults.
AB - CONTEXT: The exact relationship between the bed rest-induced loss of skeletal
muscle and reductions in muscle strength and physical performance in the older
individuals is still unclear. OBJECTIVE: We examined the effect of 10 days of bed
rest on changes in regional body composition, muscle strength, and functional
status, and the relationship between these variables in older individuals.
DESIGN, PARTICIPANTS, AND INTERVENTION: Regional body composition was measured
using dual energy x-ray absorptiometry. We also determined changes in leg
strength and several indices of functional status, including walking speed.
RESULTS: Body weight, body mass index, and total and lower extremity lean mass
decreased with bed rest. There were also significant reductions in knee extension
one repetition maximum, isometric knee extension, knee extension 60 degrees
concentric, stair ascent time, stair ascent power, stair descent time, VO2 max,
floor transfer test, 5-minute walk time, and chair stand. The overall change in
total and lower extremity lean mass was also directly related to bed rest-induced
reductions in one repetition maximum knee extension. CONCLUSIONS: Bed rest
promoted overall declines in muscle mass, muscle strength, and physical function
in older individuals. The changes in lean tissue were closely correlated with the
bed rest-induced decline of muscle strength.
PMID- 25122629
TI - Ultrasound-guided percutaneous needle electrolysis in chronic lateral
epicondylitis: short-term and long-term results.
AB - BACKGROUND: Ultrasound (US)-guided percutaneous needle electrolysis (PNE) is a
novel minimally invasive approach which consists of the application of a galvanic
current through an acupuncture needle. OBJECTIVE: To evaluate the clinical and
ultrasonographic effectiveness of a multimodal programme (PNE, eccentric exercise
(EccEx) and stretching) in the short term for patients with chronic lateral
epicondylitis, and to determine whether the clinical outcomes achieved decline
over time. METHODS: A one-way repeated measures study was performed in a clinical
setting in 36 patients presenting with lateral epicondylitis. The patients
received one session of US-guided PNE per week over 4-6 weeks, associated with a
home programme of EccEx and stretching. The main outcome measures were severity
of pain, disability (Disabilities of the Arm, Shoulder and Hand (DASH)
questionnaire), structural tendon changes (US), hypervascularity and patients'
perceptions of overall outcome. Measurements at 6, 26 and 52 weeks follow-up
included recurrence rates (increase in severity of pain or disability compared
with discharge), perception of overall outcome and success rates. RESULTS: All
outcome measures registered significant improvements between pre-intervention and
discharge. Most patients (n=30, 83.3%) rated the overall outcome as 'successful'
at 6 weeks. The ultrasonographic findings showed that the hypoechoic regions and
hypervascularity of the extensor carpi radialis brevis changed significantly. At
26 and 52 weeks, all participants (n=32) perceived a 'successful' outcome.
Recurrence rates were null after discharge and at follow-up at 6, 26 and 52
weeks. CONCLUSIONS: Symptoms and degenerative structural changes of chronic
lateral epicondylitis are reduced after US-guided PNE associated with EccEx and
stretching, with encouragingly low recurrences in the mid to long term. TRIAL
REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02085928.
PMID- 25122630
TI - The epidemiological and clinical characteristics of diarrhea associated with
enteropathogenic, enteroaggregative and diffuse-adherent Escherichia coli in
Egyptian children.
AB - A total of 220 enteroadherent Escherichia coli were identified from 729 Egyptian
children with diarrhea using the HEp-2 adherence assay. Enteropathogenic E.coli
(EPEC = 38) was common among children <6 months old and provoked vomiting, while
diffuse-adhering E.coli (DAEC = 109) induced diarrheal episodes of short
duration, and enteroaggregative E.coli (EAEC = 73) induced mild non-persistent
diarrhea. These results suggest that EPEC is associated with infantile diarrhea
in Egyptian children.
PMID- 25122632
TI - Two-year carcinogenicity study in rats with a nonnucleoside reverse transcriptase
inhibitor.
AB - Administration of lersivirine, a nonnucleotide reverse transcriptase inhibitor,
daily by oral gavage to Sprague-Dawley rats for up to 2 yr was associated with
decreased survival, decreased body weights, and an increase in neoplasms and
related proliferative lesions in the liver, thyroid, kidney, and urinary bladder.
Thyroid follicular adenoma and carcinoma, the associated thyroid follicular
hypertrophy/hyperplasia, hepatocellular adenoma/adenocarcinoma, altered cell
foci, and hepatocellular hypertrophy were consistent with lersivirine-related
induction of hepatic microsomal enzymes. Renal tubular adenoma and renal tubular
hyperplasia were attributed to the lersivirine-related exacerbation of chronic
progressive nephropathy (CPN), while urinary bladder hyperplasia and transitional
cell carcinoma in the renal pelvis and urinary bladder were attributed to urinary
calculi. Renal tubular neoplasms associated with increased incidence and severity
of CPN, neoplasms of transitional epithelium attributed to crystalluria, and
thyroid follicular and hepatocellular neoplasms related to hepatic enzyme
induction have low relevance for human risk assessment.
PMID- 25122631
TI - Tel1ATM dictates the replication timing of short yeast telomeres.
AB - Telomerase action is temporally linked to DNA replication. Although yeast
telomeres are normally late replicating, telomere shortening leads to early
firing of subtelomeric DNA replication origins. We show that double-strand breaks
flanked by short telomeric arrays cause origin firing early in S phase at late
replicating loci and that this effect on origin firing time is dependent on the
Tel1(ATM) checkpoint kinase. The effect of Tel1(ATM) on telomere replication
timing extends to endogenous telomeres and is stronger than that elicited by Rif1
loss. These results establish that Tel1(ATM) specifies not only the extent but
also the timing of telomerase recruitment.
PMID- 25122633
TI - Stability study of carboplatin infusion solutions in 0.9% sodium chloride in
polyvinyl chloride bags.
AB - BACKGROUND AND PURPOSE: Carboplatin is a platinum-containing compound with
efficacy against various malignancies. The physico-chemical stability of
carboplatin in dextrose 5% water (D5W) has been thoroughly studied; however,
there is a paucity of stability data in clinically relevant 0.9% sodium chloride
infusion solutions. The manufacturer's limited stability data in sodium chloride
solutions hampers the flexibility of carboplatin usage in oncology patients.
Hence, the purpose of this study is to determine the physical and chemical
stability of carboplatin-sodium chloride intravenous solutions under different
storage conditions. METHODS: The physico-chemical stability of 0.5 mg/mL, 2.0
mg/mL, and 4.0 mg/mL carboplatin-sodium chloride solutions prepared in polyvinyl
chloride bags was determined following storage at room temperature under ambient
fluorescent light and under refrigeration in the dark. Concentrations of
carboplatin were measured at predetermined time points up to seven days using a
stability-indicating high-performance liquid chromatography method. RESULTS: All
tested solutions were found physically stable for at least seven days. The
greatest chemical stability was observed under refrigerated storage conditions.
At 4C, all tested solutions were found chemically stable for at least seven days,
with nominal losses of <=6%. Following storage at room temperature exposed to
normal fluorescent light, the chemical stability of 0.5 mg/mL, 2.0 mg/mL, and 4.0
mg/mL solutions was three days, five days, and seven days, respectively.
CONCLUSION: The extended physico-chemical stability of carboplatin prepared in
sodium chloride reported herein permits advance preparation of these admixtures,
facilitating pharmacy utility and operations. Since no antibacterial preservative
is contained within these carboplatin solutions, we recommend storage, when
prepared under specified aseptic conditions, no greater than 24 h at room
temperature or three days under refrigeration.
PMID- 25122634
TI - Compliance with National Comprehensive Cancer Network anti-emesis guidelines in a
Community Hospital Cancer Center.
AB - OBJECTIVE: Nausea and vomiting are common adverse events exhibited by patients
receiving chemotherapy. Prophylactic use of anti-emetic agents has been shown to
reduce chemotherapy-induced nausea and vomiting. Compliance with the National
Comprehensive Cancer Network anti-emesis guidelines (Version 1.2013) by
practitioners in a community out-patient hospital (Blount Memorial Hospital) has
been reviewed and the results are presented herein. DESIGN: Retrospective study
of patients receiving their first cycle of chemotherapy. PATIENTS: A total of 487
patients were reviewed from January 2005 to July 2012. In total, 70 patients were
categorized in the high-risk category, 292 patients were categorized in the
moderate-risk category, 60 patients were categorized in the low-risk category,
and 65 patients were categorized in the minimal-risk category as per the National
Comprehensive Cancer Network guidelines. Included patients were being
administered the first cycle of their first treatment at Blount Memorial
Hospital. DATA: Data were collected retrospectively from patient chemotherapy
dispensing folders. RESULTS: In all, 63% of the patients received appropriate
anti-emetic prophylaxis medications as per the National Comprehensive Cancer
Network guidelines. Post-comparison between outcomes based on the risk category
showed that patients in the moderate-risk category were most likely (91%) and
patients in the low-risk category were least likely (6.67%) to receive
appropriate anti-emetic prophylaxis as per the National Comprehensive Cancer
Network guidelines. CONCLUSION: Overall compliance with guidelines is acceptable.
Patients in the moderate risk category are most likely to receive appropriate
anti-emetic prophylaxis.
PMID- 25122635
TI - Tranexamic acid for surgical bleeding.
PMID- 25122636
TI - Deficient human beta-defensin 1 underlies male infertility associated with poor
sperm motility and genital tract infection.
AB - Genital tract infection and reduced sperm motility are considered two pivotal
etiological factors for male infertility associated with leukocytospermia and
asthenozoospermia, respectively. We demonstrate that the amount of human beta
defensin 1 (DEFB1) in sperm from infertile men exhibiting either leukocytospermia
or asthenozoospermia, both of which are associated with reduced motility and
reduced bactericidal activity in sperm, is much lower compared to that in normal
fertile sperm. Interference with DEFB1 function also decreases both motility and
bactericidal activity in normal sperm, whereas treatment with recombinant DEFB1
markedly restores DEFB1 expression, bactericidal activity, sperm quality, and egg
penetrating ability in sperm from both asthenozoospermia and leukocytospermia
patients. DEFB1 interacts with chemokine receptor type 6 (CCR6) in sperm and
triggers Ca(2+) mobilization, which is important for sperm motility. Interference
with CCR6 function also reduces motility and bactericidal activity of normal
sperm. The present finding explains a common defect in male infertility
associated with both asthenozoospermia and leukocytospermia, indicating a dual
role of DEFB1 in defending male fertility. These results also suggest that the
expression of DEFB1 and CCR6 may have diagnostic potential and that treatment of
defective sperm with recombinant DEFB1 protein may be a feasible therapeutic
approach for male infertility associated with poor sperm motility and genital
tract infection.
PMID- 25122638
TI - A single localized dose of enzyme-responsive hydrogel improves long-term survival
of a vascularized composite allograft.
AB - Currently, systemic immunosuppression is used in vascularized composite
allotransplantation (VCA). This treatment has considerable side effects and
reduces the quality of life of VCA recipients. We loaded the immunosuppressive
drug tacrolimus into a self-assembled hydrogel, which releases the drug in
response to proteolytic enzymes that are overexpressed during inflammation. A one
time local injection of the tacrolimus-laden hydrogel significantly prolonged
graft survival in a Brown Norway-to-Lewis rat hindlimb transplantation model,
leading to a median graft survival of >100 days compared to 33.5 days in
tacrolimus only-treated recipients. Control groups with no treatment or hydrogel
only showed a graft survival of 11 days. Histopathological evaluation, including
anti-graft antibodies and complement C3, revealed significantly reduced immune
responses in the tacrolimus-hydrogel group compared with tacrolimus only. In
conclusion, a single-dose local injection of an enzyme-responsive tacrolimus
hydrogel is capable of preventing VCA rejection for >100 days in a rat model and
may offer a new approach for immunosuppression in VCA.
PMID- 25122637
TI - Lymph node fibroblastic reticular cell transplants show robust therapeutic
efficacy in high-mortality murine sepsis.
AB - Sepsis is an aggressive inflammatory syndrome and a global health burden
estimated to kill 7.3 million people annually. Single-target molecular therapies
have not addressed the multiple disease pathways triggered by septic injury. Cell
therapies might offer a broader set of mechanisms of action that benefit complex,
multifocal disease processes. We describe a population of immune-specialized
myofibroblasts derived from lymph node tissue, termed fibroblastic reticular
cells (FRCs). Because FRCs have an immunoregulatory function in lymph nodes, we
hypothesized that ex vivo-expanded FRCs would control inflammation when
administered therapeutically. Indeed, a single injection of ex vivo-expanded
allogeneic FRCs reduced mortality in mouse models of sepsis when administered at
early or late time points after septic onset. Mice treated with FRCs exhibited
lower local and systemic concentrations of proinflammatory cytokines and reduced
bacteremia. When administered 4 hours after induction of lipopolysaccharide
endotoxemia, or cecal ligation and puncture (CLP) sepsis in mice, FRCs reduced
deaths by at least 70%. When administered late in disease (16 hours after CLP),
FRCs still conveyed a robust survival advantage (44% survival compared to 0% for
controls). FRC therapy was dependent on the metabolic activity of nitric oxide
synthase 2 (NOS2) as the primary molecular mechanism of drug action in the mice.
Together, these data describe a new anti-inflammatory cell type and provide
preclinical evidence for therapeutic efficacy in severe sepsis that warrants
further translational study.
PMID- 25122641
TI - Translational pain research: Lessons from genetics and genomics.
AB - Pharmacological, surgical, psychological, and alternative medicine approaches for
the treatment of chronic pain, including neuropathic pain, provide only partial
relief for most patients, with the efficacy of existing medications often blunted
by dose-limiting side effects arising from drug actions on cells outside the pain
signaling axis. The development of more effective treatments for pain-
particularly chronic pain states such as neuropathic pain--has been hampered by
lack of predictive animal models and biomarkers, variation in pain
characteristics between patients or on a day-to-day basis for single patients,
patient stratification on the basis of symptoms rather than mechanism, and a high
rate of placebo responses. We discuss genetic and genomic approaches to
translational pain research. We review examples of the identification and
validation of human pain targets through rodent genome-wide association studies
(GWAS) and global mRNA expression studies, functional screening in flies and
mice, human GWAS and whole-exome sequencing studies, and the targeted candidate
gene approach. These and other emerging genetic and genomic strategies are likely
to facilitate the development of new, more effective pain therapeutics.
PMID- 25122639
TI - Intratumoral injection of Clostridium novyi-NT spores induces antitumor
responses.
AB - Species of Clostridium bacteria are notable for their ability to lyse tumor cells
growing in hypoxic environments. We show that an attenuated strain of Clostridium
novyi (C. novyi-NT) induces a microscopically precise, tumor-localized response
in a rat orthotopic brain tumor model after intratumoral injection. It is well
known, however, that experimental models often do not reliably predict the
responses of human patients to therapeutic agents. We therefore used naturally
occurring canine tumors as a translational bridge to human trials. Canine tumors
are more like those of humans because they occur in animals with heterogeneous
genetic backgrounds, are of host origin, and are due to spontaneous rather than
engineered mutations. We found that intratumoral injection of C. novyi-NT spores
was well tolerated in companion dogs bearing spontaneous solid tumors, with the
most common toxicities being the expected symptoms associated with bacterial
infections. Objective responses were observed in 6 of 16 dogs (37.5%), with three
complete and three partial responses. On the basis of these encouraging results,
we treated a human patient who had an advanced leiomyosarcoma with an
intratumoral injection of C. novyi-NT spores. This treatment reduced the tumor
within and surrounding the bone. Together, these results show that C. novyi-NT
can precisely eradicate neoplastic tissues and suggest that further clinical
trials of this agent in selected patients are warranted.
PMID- 25122642
TI - Does a single dose of intravenous dexamethasone reduce Symptoms in Emergency
department patients with low Back pain and RAdiculopathy (SEBRA)? A double-blind
randomised controlled trial.
AB - OBJECTIVE: To assess the effect of a single dose of intravenous dexamethasone in
addition to routine treatment on visual analogue scale (VAS) pain scores at 24 h
in emergency department (ED) patients with low back pain with radiculopathy
(LBPR). METHODS: Double-blind randomised controlled trial of 58 adult ED patients
with LBPR, conducted in one tertiary and one urban ED. The intervention was 8 mg
of intravenous dexamethasone (or placebo) in addition to current routine care.
The primary outcome was the change in VAS pain scores between presentation and 24
h. Secondary outcomes included VAS pain scores at 6 weeks, ED length of stay
(EDLOS), straight leg raise (SLR) angles and Oswestry functional scores. RESULTS:
Patients treated with dexamethasone had a 1.86 point (95% CI 0.31 to 3.42,
p=0.019) greater reduction in VAS pain scores at 24 h than placebo
(dexamethasone: -2.63 (95% CI -3.63 to -1.63) versus placebo: -0.77 (95% CI -2.04
to 0.51)). At 6 weeks, both groups had similar significant and sustained decrease
in VAS scores compared with baseline. Patients receiving dexamethasone had a
significantly shorter EDLOS (median: 3.5 h vs 18.8 h, p=0.049) and improved SLR
angle at discharge (14.7 degrees , p=0.040). There was no difference in
functional scores. CONCLUSIONS: In patients with LBPR, a single dose of
intravenous dexamethasone in addition to routine management improved VAS pain
scores at 24 h, but this effect was not statistically significant at 6 weeks.
Dexamethasone may reduce EDLOS and can be considered as a safe adjunct to
standard treatment. TRIAL REGISTRATION NUMBER: ACTRN12611001020976.
PMID- 25122643
TI - Analysis of mandibular structure using 3D facial computed tomography.
AB - OBJECTIVE: This study measured and analyzed the position and dimension of genial
tubercle (GT) and mental foramen (MF) STUDY DESIGN: Retrospective chart review
study. SETTING: Tertiary care teaching hospital. SUBJECTS AND METHODS: Two
hundred ten subjects were included who received 3-dimensional (3D) facial
computed tomography (CT), and the GT and MF were evaluated. Subjects were divided
into 4 groups by gender and skeletal type. Seven variables were measured: (1)
height of GT (GTH), (2) width of GT (GTW), (3) distance from apices of lower
incisors to superior border of GT (LI-SGT), (4) distance from inferior border of
GT to inferior border of mandible (IGT-IBM), (5) thickness of anterior mandible
(MT), (6) distance from symphysis of mandible to MF (S-MF), and (7) distance from
superior border of GT to inferior border of mandible (SGT-IBM). RESULTS: All the
parameters showed marked differences in individuals. Class I males showed longer
GTH, MT, and SGT-IBM than class I females (P < .05). IGT-IBM and S-MF were longer
in class II males than in class I females (P < .05). LI-SGT and IGT-IBM also
showed personal variation. CONCLUSION: Anatomical features of mandibular
structures showed individual variations. GTH, IGT-IBM, MT, S-MF, and SGT-IBM also
showed differences between the groups.
PMID- 25122644
TI - High-salt intake induces cardiomyocyte hypertrophy in rats in response to local
angiotensin II type 1 receptor activation.
AB - Many studies have shown that risk factors that are independent of blood pressure
(BP) can contribute to the development of cardiac hypertrophy (CH). Among these
factors, high-salt (HS) intake was prominent. Although some studies have
attempted to elucidate the role of salt in the development of this disease, the
mechanisms by which salt acts are not yet fully understood. Thus, the aim of this
study was to better understand the mechanisms of CH and interstitial fibrosis
(IF) caused by HS intake. Male Wistar rats were divided into 5 groups according
to diet [normal salt (NS; 1.27% NaCl) or HS (8% NaCl)] and treatment [losartan
(LOS) (HS+LOS group), hydralazine (HZ) (HS+HZ group), or N-acetylcysteine (NAC)
(HS+NAC group)], which was given in the drinking water. Tail-cuff BP, transverse
diameter of the cardiomyocyte, IF, angiotensin II type 1 receptor (AT1) gene and
protein expression, serum aldosterone, cardiac angiotensin II, cardiac
thiobarbituric acid-reactive substances, and binding of conformation-specific
anti-AT1 and anti-angiotensin II type 2 receptor (AT2) antibodies in the 2
ventricles were measured. Based on the left ventricle transverse diameter data,
the primary finding was the occurrence of significant BP-independent CH in the
HS+HZ group (96% of the HS group) and a partial or total prevention of such
hypertrophy via treatment with NAC or LOS (81% and 67% of the HS group,
respectively). The significant total or partial prevention of IF using all 3
treatments (HS+HZ, 27%; HS+LOS, 27%; and HS+NAC, 58% of the HS group,
respectively), and an increase in the AT1 gene and protein expression and
activity in groups that developed CH, confirmed that CH occurred via the AT1 in
this experimental model. Thus, this study unveiled some relevant previously
unknown mechanisms of CH induced by chronic HS intake in Wistar rats. The link of
oxidative stress with CH in our experimental model is very interesting and
stimulates further evaluation for its full comprehension.
PMID- 25122640
TI - Lost but making progress--Where will new analgesic drugs come from?
AB - There is a critical need for effective new pharmacotherapies for pain. The
paucity of new drugs successfully reaching the clinic calls for a reassessment of
current analgesic drug discovery approaches. Many points early in the discovery
process present significant hurdles, making it critical to exploit advances in
pain neurobiology to increase the probability of success. In this review, we
highlight approaches that are being pursued vigorously by the pain community for
drug discovery, including innovative preclinical pain models, insights from
genetics, mechanistic phenotyping of pain patients, development of biomarkers,
and emerging insights into chronic pain as a disorder of both the periphery and
the brain. Collaborative efforts between pharmaceutical, academic, and public
entities to advance research in these areas promise to de-risk potential targets,
stimulate investment, and speed evaluation and development of better pain
therapies.
PMID- 25122646
TI - Glycine stimulates protein synthesis and inhibits oxidative stress in pig small
intestinal epithelial cells.
AB - Glycine has recently been classified as a nutritionally essential amino acid for
maximal growth in young pigs. Currently, little is known about the metabolism or
function of glycine in the neonatal intestine. This work was conducted to test
the hypothesis that glycine has a protective effect against oxidative stress in
intestinal epithelial cells. Jejunal enterocytes isolated from newborn pigs were
cultured in the presence of 0.0-2 mmol/L glycine for measurements of glycine
metabolism, cell proliferation, protein turnover, apoptosis, and antioxidative
response. Compared with 0.0-0.5 mmol/L glycine, 1.0 mmol/L glycine enhanced (P <
0.05) cell growth (by 8-24% on day 2 and by 34-224% on day 4, respectively) and
protein synthesis (by 36-419%) while reducing (P < 0.05) protein degradation (by
7-28%). This effect of glycine was associated with activation of the mammalian
target of rapamycin signaling pathway in enterocytes. By using a model of
oxidative stress induced by 30 MUmol/L 4-hydroxynonenal (4-HNE), which was
assessed by flow cytometry analysis, 1.0 mmol/L glycine inhibited (P < 0.05)
activation of caspase 3 by 25% and attenuated (P < 0.05) 4-HNE-induced apoptosis
by 38% in intestinal porcine epithelial cell line 1 cells through promotion of
reduced glutathione synthesis and expression of glycine transporter 1 while
reducing the activation of extracellular signal-regulated kinases, c-Jun amino
terminal kinases, and p38 protein in the mitogen-activated protein kinase
signaling pathway. These novel findings provide a biochemical mechanism for the
use of dietary glycine to improve intestinal health in neonates under conditions
of oxidative stress and glycine deficiency.
PMID- 25122645
TI - MicroRNAs are absorbed in biologically meaningful amounts from nutritionally
relevant doses of cow milk and affect gene expression in peripheral blood
mononuclear cells, HEK-293 kidney cell cultures, and mouse livers.
AB - BACKGROUND: MicroRNAs (miRNAs) regulate genes in animals and plants and can be
synthesized endogenously. In milk, miRNAs are encapsulated in exosomes, thereby
conferring protection against degradation and facilitating uptake by endocytosis.
The majority of bovine miRNAs have nucleotide sequences complementary to human
gene transcripts, suggesting that miRNAs in milk might regulate human genes.
OBJECTIVES: We tested the hypotheses that humans absorb biologically meaningful
amounts of miRNAs from nutritionally relevant doses of milk, milk-borne miRNAs
regulate human gene expression, and mammals cannot compensate for dietary miRNA
depletion by endogenous miRNA synthesis. METHODS: Healthy adults (3 men, 2 women;
aged 26-49 y) consumed 0.25, 0.5, and 1.0 L of milk in a randomized crossover
design. Gene expression studies and milk miRNA depletion studies were conducted
in human cell cultures and mice, respectively. For comparison, feeding studies
with plant miRNAs from broccoli were conducted in humans. RESULTS: Postprandial
concentration time curves suggest that meaningful amounts of miRNA (miR)-29b and
miR-200c were absorbed; plasma concentrations of miR-1 did not change (negative
control). The expression of runt-related transcription factor 2 (RUNX2), a known
target of miR-29b, increased by 31% in blood mononuclear cells after milk
consumption compared with baseline. When milk exosomes were added to cell culture
media, mimicking postprandial concentrations of miR-29b and miR-200c, reporter
gene activities significantly decreased by 44% and 17%, respectively, compared
with vehicle controls in human embryonic kidney 293 cells. When C57BL/6J mice
were fed a milk miRNA-depleted diet for 4 wk, plasma miR-29b concentrations were
significantly decreased by 61% compared with miRNA-sufficient controls, i.e.,
endogenous synthesis did not compensate for dietary depletion. Broccoli sprout
feeding studies were conducted as a control and elicited no detectable increase
in Brassica-specific miRNAs. CONCLUSION: We conclude that miRNAs in milk are
bioactive food compounds that regulate human genes.
PMID- 25122648
TI - Low doses of eicosapentaenoic acid and docosahexaenoic acid from fish oil dose
dependently decrease serum triglyceride concentrations in the presence of plant
sterols in hypercholesterolemic men and women.
AB - Plant sterols (PSs) lower LDL cholesterol (LDL-C) concentrations, whereas the n-3
(omega-3) fish fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid
(DHA) lower triglyceride (TG) concentrations. Incorporating both PSs and EPA+DHA
from fish oil (FO) in a single food format was expected to beneficially affect 2
blood lipid risk factors. The aim of this study was to investigate the dose
response relation between low doses (<2 g/d) of EPA+DHA from FO, incorporated in
a low-fat PS-enriched spread, and TG concentrations. In addition, effects on LDL
C were investigated. The study was designed as a randomized, double-blind,
placebo-controlled parallel study. After a 4-wk run-in period, subjects were
randomly assigned to consume either a control (C) spread (no PSs, no FO) or 1 of
4 intervention spreads containing a fixed amount of PSs (2.5 g/d) and varying
amounts of FO (0.0, 0.9, 1.3, and 1.8 g/d of EPA+DHA) for 4 wk. Before and after
the intervention, fasting blood samples were drawn for measuring serum lipids and
EPA and DHA in erythrocyte membranes. In total, 85 hypercholesterolemic men and
247 women with a mean age of 57.9 y (range: 25-74 y) were included. Eighteen
subjects dropped out during the study. At baseline, mean TG and LDL-C
concentrations were 1.09 and 4.00 mmol/L, respectively. After the intervention, a
significant dose-response relation for the TG-lowering effect of EPA+DHA [betaln
(TG) = -0.07 mmol/L per gram of EPA+DHA; P < 0.01] was found. Compared with the C
group, TG concentrations were 9.3-16.2% lower in the different FO groups (P <
0.05 for all groups). LDL-C concentrations were 11.5-14.7% lower in the different
PS groups than in the C group (P < 0.01 for all groups). EPA and DHA in
erythrocyte membranes were dose-dependently higher after FO intake than after the
C spread, indicating good compliance. Consumption of a low-fat spread enriched
with PSs and different low doses of n-3 fatty acids from FO decreased TG
concentrations in a dose-dependent manner and decreased LDL-C concentrations.
This trial was registered at clinicaltrials.gov as NCT01313988.
PMID- 25122649
TI - Computer modeling of obesity links theoretical energetic measures with
experimental measures of fuel use for lean and obese men.
AB - The goal of this research was to use a computational model of human metabolism to
predict energy metabolism for lean and obese men. The model is composed of 6
state variables representing amino acids, muscle protein, visceral protein,
glucose, triglycerides, and fatty acids (FAs). Differential equations represent
carbohydrate, amino acid, and FA uptake and output by tissues based on ATP
creation and use for both lean and obese men. Model parameterization is based on
data from previous studies. Results from sensitivity analyses indicate that model
predictions of resting energy expenditure (REE) and respiratory quotient (RQ) are
dependent on FA and glucose oxidation rates with the highest sensitivity
coefficients (0.6, 0.8 and 0.43, 0.15, respectively, for lean and obese models).
Metabolizable energy (ME) is influenced by ingested energy intake with a
sensitivity coefficient of 0.98, and a phosphate-to-oxygen ratio by FA oxidation
rate and amino acid oxidation rate (0.32, 0.24 and 0.55, 0.65 for lean and obese
models, respectively). Simulations of previously published studies showed that
the model is able to predict ME ranging from 6.6 to 9.3 with 0% differences
between published and model values, and RQ ranging from 0.79 to 0.86 with 1%
differences between published and model values. REEs >7 MJ/d are predicted with
6% differences between published and model values. Glucose oxidation increases by
~0.59 mol/d, RQ increases by 0.03, REE increases by 2 MJ/d, and heat production
increases by 1.8 MJ/d in the obese model compared with lean model simulations.
Increased FA oxidation results in higher changes in RQ and lower relative changes
in REE. These results suggest that because fat mass is directly related to REE
and rate of FA oxidation, body fat content could be used as a predictor of RQ.
PMID- 25122647
TI - Pregnancy and lactation alter biomarkers of biotin metabolism in women consuming
a controlled diet.
AB - BACKGROUND: Biotin functions as a cofactor for several carboxylase enzymes with
key roles in metabolism. At present, the dietary requirement for biotin is
unknown and intake recommendations are provided as Adequate Intakes (AIs). The
biotin AI for adults and pregnant women is 30 MUg/d, whereas 35 MUg/d is
recommended for lactating women. However, pregnant and lactating women may
require more biotin to meet the demands of these reproductive states. OBJECTIVE:
The current study sought to quantify the impact of reproductive state on biotin
status response to a known dietary intake of biotin. METHODS: To achieve this
aim, we measured a panel of biotin biomarkers among pregnant (gestational week 27
at study entry; n = 26), lactating (postnatal week 5 at study entry; n = 28), and
control (n = 21) women who participated in a 10- to 12-wk feeding study providing
57 MUg of dietary biotin/d as part of a mixed diet. RESULTS: Over the course of
the study, pregnant women excreted 69% more (vs. control; P < 0.001) 3
hydroxyisovaleric acid (3-HIA), a metabolite that accumulates during the
catabolism of leucine when the activity of biotin-dependent methylcrotonyl
coenzyme A carboxylase is impaired. Interestingly, urinary excretion of 3
hydroxyisovaleryl-carnitine (3-HIA-carnitine), a downstream metabolite of 3-HIA,
was 27% lower (P = 0.05) among pregnant (vs. control) women, a finding that may
arise from carnitine inadequacy during gestation. No differences (P > 0.05) were
detected in plasma biotin, urinary biotin, or urinary bisnorbiotin between
pregnant and control women. Lactating women excreted 76% more (vs. control; P =
0.001) of the biotin catabolite bisnorbiotin, indicating that lactation
accelerates biotin turnover and loss. Notably, with respect to control women,
lactating women excreted 23% less (P = 0.04) urinary 3-HIA and 26% less (P =
0.05) urinary 3-HIA-carnitine, suggesting that lactation reduces leucine
catabolism and that these metabolites may not be useful indicators of biotin
status during lactation. CONCLUSIONS: Overall, these data demonstrate significant
alterations in markers of biotin metabolism during pregnancy and lactation and
suggest that biotin intakes exceeding current recommendations are needed to meet
the demands of these reproductive states. This trial was registered at
clinicaltrials.gov as NCT01127022.
PMID- 25122651
TI - Fatty Acid Binding Protein 3 Is Involved in n-3 and n-6 PUFA transport in mouse
trophoblasts.
AB - BACKGROUND: Low placental fatty acid (FA) transport during the embryonic period
has been suggested to result in fetal developmental disorders and various adult
metabolic diseases, but the molecular mechanism by which FAs are transported
through the placental unit remains largely unknown. OBJECTIVE: The aim of this
study was to examine the distribution and functional relevance of FA binding
protein (FABP), a cellular chaperone of FAs, in the mouse placenta. METHODS: We
clarified the localization of FABPs and sought to examine their function in
placental FA transport through the phenotypic analysis of Fabp3-knockout mice.
RESULTS: Four FABPs (FABP3, FABP4, FABP5, and FABP7) were expressed with spatial
heterogeneity in the placenta, and FABP3 was dominantly localized to the
trophoblast cells. In placentas from the Fabp3-knockout mice (both sexes), the
transport coefficients for linoleic acid (LA) were significantly reduced compared
with those from wild-type mice by 25% and 44% at embryonic day (E) 15.5 and
E18.5, respectively, whereas those for alpha-linolenic acid (ALA) were reduced by
19% and 17%, respectively. The accumulation of LA (18% and 27% at E15.5 and
E18.5) and ALA (16% at E15.5) was also significantly less in the Fabp3-knockout
fetuses than in wild-type fetuses. In contrast, transport and accumulation of
palmitic acid (PA) were unaffected and glucose uptake significantly increased by
23% in the gene-ablated mice compared with wild-type mice at E18.5. Incorporation
of LA (51% and 52% at 1 and 60 min, respectively) and ALA (23% at 60 min), but
not PA, was significantly less in FABP3-knockdown BeWo cells than in controls,
whereas glucose uptake was significantly upregulated by 51%, 50%, 31%, and 33% at
1, 20, 40, and 60 min, respectively. CONCLUSIONS: Collectively FABP3 regulates n
3 (omega-3) and n-6 (omega-6) polyunsaturated FA transport in trophoblasts and
plays a pivotal role in fetal development.
PMID- 25122650
TI - Gestational iron deficiency is associated with pica behaviors in adolescents.
AB - A relation between pica (the craving and purposive consumption of nonfood items)
during pregnancy and anemia is observed frequently. However, few studies related
pica behaviors to biomarkers of iron status, and little is known about pica
prevalence in U.S. pregnant adolescents. To address this, we undertook a
longitudinal study examining iron status and pica behaviors among a group of 158
pregnant adolescents (aged <=18 y). Approximately two-thirds of the participants
were African American and 25% were Hispanic. Maternal iron status indicators
[hemoglobin, soluble transferrin receptor, serum ferritin (SF), total body iron
(TBI), and serum hepcidin] were assessed during pregnancy (18.5-37.3 wk) and at
delivery. Pica behavior was assessed up to 3 times across gestation. Among the
158 adolescents, 46% reported engaging in pica behavior. Substances ingested
included ice (37%), starches (8%), powders (4%), and soap (3%). During pregnancy,
mean SF [geometric mean: 13.6 MUg/L (95% CI: 11.0, 17.0 MUg/L)], TBI (mean +/-
SD: 2.5 +/- 4.2 mg/kg), and hepcidin [geometric mean: 19.1 MUg/L (95% CI: 16.3,
22.2 MUg/L)] concentrations were significantly lower (P < 0.05) in the pica group
(n = 72) than values observed among the non-pica group [SF, geometric mean: 21.1
MUg/L (95% CI: 18.0, 25.0 MUg/L); TBI, mean +/- SD: 4.3 +/- 3.5 mg/kg; hepcidin,
geometric mean: 27.1 MUg/L (95%: 23.1, 32.1 MUg/L); n = 86]. Although additional
studies must address the etiology of these relations, this practice should be
screened for, given its association with low iron status and because many of the
substances ingested may be harmful. This trial was registered at
clinicaltrials.gov as NCT01019902.
PMID- 25122652
TI - The development of halophyte-based agriculture: past and present.
AB - BACKGROUND: Freshwater comprises about a mere 2.5% of total global water, of
which approximately two-thirds is locked into glaciers at the polar ice caps and
on mountains. In conjunction with this, in many instances irrigation with
freshwater causes an increase in soil salinity due to overirrigation of
agricultural land, inefficient water use and poor drainage of unsuitable soils.
The problem of salinity was recognized a long time ago and, due to the importance
of irrigated agriculture, numerous efforts have been devoted towards improving
crop species for better utilization of saline soils and water. Irrigating plants
with saline water is a challenge for practitioners and researchers throughout the
world. SCOPE: Recruiting wild halophytes with economic potential was suggested
several decades ago as a way to reduce the damage caused by salinization of soil
and water. A range of cultivation systems for the utilization of halophytes have
been developed, for the production of biofuel, purification of saline effluent in
constructed wetlands, landscaping, cultivation of gourmet vegetables, and more.
This review critically analyses past and present halophyte-based production
systems in the context of genetics, physiology, agrotechnical issues and product
value. There are still difficulties that need to be overcome, such as direct
germination in saline conditions or genotype selection. However, more and more
research is being directed not only towards determining salt tolerance of
halophytes, but also to the improvement of agricultural traits for long-term
progress.
PMID- 25122653
TI - Resin duct size and density as ecophysiological traits in fire scars of
Pseudotsuga menziesii and Larix occidentalis.
AB - BACKGROUND AND AIMS: Resin ducts (RDs) are features present in most conifer
species as defence structures against pests and pathogens; however, little is
known about RD expression in trees following fire injury. This study investigates
changes in RD size and density in fire scars of Douglas fir (Pseudotsuga
menziesii) and western larch (Larix occidentalis) as a means to evaluate the
ecophysiological significance of traumatic resinosis for tree defence and
survival. METHODS: Transverse and tangential microsections were prepared for
light microscopy and image analysis in order to analyse axial and radial RDs,
respectively. Epithelial cells of RDs and fusiform rays associated with radial
RDs were also examined. RDs were compared between normal xylem and wound xylem at
four different section heights along the fire-injured stem. KEY RESULTS:
Following fire injury, P. menziesii axial RDs narrowed by 38-43 % in the first
year after injury, and the magnitude of this change increased with stem height.
Larix occidentalis axial RDs widened by 46-50 % in the second year after injury.
Radial RDs were of equivalent size in P. menziesii, but widened by 162-214 % in
L. occidentalis. Fusiform rays were larger following fire injury, by 4-14 % in P.
menziesii and by 23-38 % in L. occidentalis. Furthermore, axial RD density
increased in both species due to the formation of tangential rows of traumatic
RDs, especially in the first and second years after injury. However, radial RD
density did not change significantly. CONCLUSIONS: These results highlight
traumatic resinosis as a species-specific response. Pseudotsuga menziesii produce
RDs of equivalent or reduced size, whereas L. occidentalis produce wider RDs in
both the axial and radial duct system, thereby increasing resin biosynthesis and
accumulation within the whole tree. Larix occidentalis thus appears to allocate
more energy to defence than P. menziesii.
PMID- 25122654
TI - Labellar anatomy and secretion in Bulbophyllum Thouars (Orchidaceae:
Bulbophyllinae) sect. Racemosae Benth. & Hook. f.
AB - BACKGROUND AND AIMS: Floral secretions are common in Bulbophyllum Thouars, and
the labella of a number of Asian species are said to produce secretions rich in
lipids that act as food rewards for insect pollinators. Although some of these
reports are based on simple histochemical tests, a much greater number are
anecdotal and, hitherto, neither the ultrastructure of the labellum nor the
secretory process has been investigated in detail. Furthermore, sophisticated
histochemical approaches have generally not been applied. Here, both the labellar
structure and the secretory process are investigated for four species of Asian
Bulbophyllum sect. Racemosae Benth. & Hook. f., namely Bulbophyllum careyanum
(Hook.) Spreng., B. morphologorum Kraenzl., B. orientale Seidenf. and B.
wangkaense Seidenf., and compared with those of unequivocal lipid-secreting
orchids. METHODS: Labellar, secretory tissue was investigated using light
microscopy, scanning electron microscopy, transmission electron microscopy and
histochemistry. KEY RESULTS: The adaxial median longitudinal groove of the
labellum contained secretory tissue comprising palisade-like epidermal cells,
similar to those of certain lipid-secreting Oncidiinae Benth. However, these
cells and their secretions gave positive results mainly for protein and mucilage,
and their organelle complement was consistent with that of cells involved in
protein and mucilage synthesis. Sub-cuticular accumulation of secretion resulted
in cuticular distension and blistering. The sub-epidermal layer of isodiametric
parenchyma contained starch and, like the epidermal cells, ultrastructure
consistent with mucilage synthesis. Lipids were mainly confined to the cuticle,
and hardly any intracellular lipid droplets were observed. CONCLUSIONS: It is
proposed that mucilage is produced by dictyosomes present in the palisade-like
epidermal cells. Mucilage precursors may also be produced by these same
organelles in sub-epidermal cells and are thought to pass along the symplast via
plasmodesmata into the adjoining palisade-like secretory cells, which contain
abundant arrays of rough endoplasmic reticulum. Here, they become chemically
modified and form a protein-rich, mucilaginous secretion that, following vesicle
mediated transport across the cytoplasm, traverses the cell wall and accumulates
in blisters formed from the distended cuticle. Rupture of these blisters releases
the secretion onto the labellar surface. However, in certain species, there is
some evidence that the secretion may traverse the cuticle via cuticular pores,
and micro-channels may permit the passage of fragrance. Hydrolysis of sub
epidermal starch probably generates the carbohydrate and, together with
mitochondria, much of the energy required for the secretory process. This
anatomical organization resembles that found in certain lipid-secreting,
Neotropical species of Bulbophyllum and Oncidiinae, but since the chemical
composition of their secretions is different, and these taxa occur on a separate
continent and have different insect pollinators, parallelism of floral anatomy is
likely.
PMID- 25122655
TI - Responses to shading of naturalized and non-naturalized exotic woody species.
AB - BACKGROUND AND AIMS: Recent studies have suggested that responses to shading
gradients may play an important role in establishment success of exotic plants,
but hitherto few studies have tested this. Therefore, a common-garden experiment
was conducted using multiple Asian woody plant species that were introduced to
Europe >100 years ago in order to test whether naturalized and non-naturalized
species differ in their responses to shading. Specifically, a test was carried
out to determine whether naturalized exotic woody species maintained better
growth under shaded conditions, and whether they expressed greater (morphological
and physiological) adaptive plasticity in response to shading, relative to non
naturalized species. METHODS: Nineteen naturalized and 19 non-naturalized exotic
woody species were grown under five light levels ranging from 100 to 7 % of
ambient light. For all plants, growth performance (i.e. biomass), morphological
and CO2 assimilation characteristics were measured. For the CO2 assimilation
characteristics, CO2 assimilation rate was measured at 1200 MUmol m(-2) s(-1)
(i.e. saturated light intensity, A1200), 50 MUmol m(-2) s(-1) (i.e. low light
intensity, A50) and 0 MUmol m(-2) s(-1) (A0, i.e. dark respiration). KEY RESULTS:
Overall, the naturalized and non-naturalized species did not differ greatly in
biomass production and measured morphological and CO2 assimilation
characteristics across the light gradient. However, it was found that naturalized
species grew taller and reduced total leaf area more than non-naturalized species
in response to shading. It was also found that naturalized species were more
capable of maintaining a high CO2 assimilation rate at low light intensity (A50)
when grown under shading. CONCLUSIONS: The results indicate that there is no
clear evidence that the naturalized species possess a superior response to
shading over non-naturalized species, at least not at the early stage of their
growth. However, the higher CO2 assimilation capacity of the naturalized species
under low-light conditions might facilitate early growth and survival, and
thereby ultimately favour their initial population establishment over the non
naturalized species.
PMID- 25122657
TI - Modelling biomechanics of bark patterning in grasstrees.
AB - BACKGROUND AND AIMS: Bark patterns are a visually important characteristic of
trees, typically attributed to fractures occurring during secondary growth of the
trunk and branches. An understanding of bark pattern formation has been hampered
by insufficient information regarding the biomechanical properties of bark and
the corresponding difficulties in faithfully modelling bark fractures using
continuum mechanics. This study focuses on the genus Xanthorrhoea (grasstrees),
which have an unusual bark-like structure composed of distinct leaf bases
connected by sticky resin. Due to its discrete character, this structure is well
suited for computational studies. METHODS: A dynamic computational model of
grasstree development was created. The model captures both the phyllotactic
pattern of leaf bases during primary growth and the changes in the trunk's width
during secondary growth. A biomechanical representation based on a system of
masses connected by springs is used for the surface of the trunk, permitting the
emergence of fractures during secondary growth to be simulated. The resulting
fracture patterns were analysed statistically and compared with images of real
trees. KEY RESULTS: The model reproduces key features of grasstree bark patterns,
including their variability, spanning elongated and reticulate forms. The
patterns produced by the model have the same statistical character as those seen
in real trees. CONCLUSIONS: The model was able to support the general hypothesis
that the patterns observed in the grasstree bark-like layer may be explained in
terms of mechanical fractures driven by secondary growth. Although the generality
of the results is limited by the unusual structure of grasstree bark, it supports
the hypothesis that bark pattern formation is primarily a biomechanical
phenomenon.
PMID- 25122656
TI - Contribution of above- and below-ground plant traits to the structure and
function of grassland soil microbial communities.
AB - BACKGROUND AND AIMS: Abiotic properties of soil are known to be major drivers of
the microbial community within it. Our understanding of how soil microbial
properties are related to the functional structure and diversity of plant
communities, however, is limited and largely restricted to above-ground plant
traits, with the role of below-ground traits being poorly understood. This study
investigated the relative contributions of soil abiotic properties and plant
traits, both above-ground and below-ground, to variations in microbial processes
involved in grassland nitrogen turnover. METHODS: In mountain grasslands
distributed across three European sites, a correlative approach was used to
examine the role of a large range of plant functional traits and soil abiotic
factors on microbial variables, including gene abundance of nitrifiers and
denitrifiers and their potential activities. KEY RESULTS: Direct effects of soil
abiotic parameters were found to have the most significant influence on the
microbial groups investigated. Indirect pathways via plant functional traits
contributed substantially to explaining the relative abundance of fungi and
bacteria and gene abundances of the investigated microbial communities, while
they explained little of the variance in microbial activities. Gene abundances of
nitrifiers and denitrifiers were most strongly related to below-ground plant
traits, suggesting that they were the most relevant traits for explaining
variation in community structure and abundances of soil microbes involved in
nitrification and denitrification. CONCLUSIONS: The results suggest that
consideration of plant traits, and especially below-ground traits, increases our
ability to describe variation in the abundances and the functional
characteristics of microbial communities in grassland soils.
PMID- 25122658
TI - Mitochondrial defects and neuromuscular degeneration caused by altered expression
of Drosophila Gdap1: implications for the Charcot-Marie-Tooth neuropathy.
AB - One of the genes involved in Charcot-Marie-Tooth (CMT) disease, an inherited
peripheral neuropathy, is GDAP1. In this work, we show that there is a true
ortholog of this gene in Drosophila, which we have named Gdap1. By up- and down
regulation of Gdap1 in a tissue-specific manner, we show that altering its levels
of expression produces changes in mitochondrial size, morphology and
distribution, and neuronal and muscular degeneration. Interestingly, muscular
degeneration is tissue-autonomous and not dependent on innervation. Metabolic
analyses of our experimental genotypes suggest that alterations in oxidative
stress are not a primary cause of the neuromuscular degeneration but a long-term
consequence of the underlying mitochondrial dysfunction. Our results contribute
to a better understanding of the role of mitochondria in CMT disease and pave the
way to generate clinically relevant disease models to study the relationship
between mitochondrial dynamics and peripheral neurodegeneration.
PMID- 25122659
TI - Absence of ALOX5 gene prevents stress-induced memory deficits, synaptic
dysfunction and tauopathy in a mouse model of Alzheimer's disease.
AB - Although the initial events of Alzheimer's disease (AD) are still not known, it
is clear that the disease in its sporadic form results from the combination of
genetic and environmental risk factors. Among the latter, behavioral stress has
been increasingly recognized as an important factor in the propagation of AD.
However, the mechanisms underlying this modulation remain to be fully
investigated. Since stress up-regulates the ALOX5 gene product, 5-lipoxygenase
(5LO), herein we investigated its role in modulating stress-dependent development
of the AD phenotype. To reach this goal, triple transgenic (3xTg) mice and 3xTg
genetically deficient for 5LO were investigated after undergoing a
restraint/isolation paradigm. In the present paper, we found that 28 days of
restraint/isolation stress worsened tau phosphorylation and solubility, increased
glycogen synthase kinase 3beta activity, compromised long-term potentiation and
impaired fear-conditioned memory recall in 3xTg animals, but not in 3xTg animals
lacking 5LO (3xTg/5LO-/-). These results highlight the novel functional role that
the ALOX5 gene plays in the development of the biochemical, electrophysiological
and behavioral sequelae of stress in the AD context. They provide critical
support that this gene and its expressed protein are viable therapeutic targets
to prevent the onset or delay the progression of AD in individuals exposed to
this risk factor.
PMID- 25122660
TI - Synergic prodegradative activity of Bicalutamide and trehalose on the mutant
androgen receptor responsible for spinal and bulbar muscular atrophy.
AB - Spinal and bulbar muscular atrophy (SBMA) is an X-linked motoneuron disease due
to a CAG triplet-repeat expansion in the androgen receptor (AR) gene, which is
translated into an elongated polyglutamine (polyQ) tract in AR protein (ARpolyQ).
ARpolyQ toxicity is activated by the AR ligand testosterone (or
dihydrotestosterone), and the polyQ triggers ARpolyQ misfolding and aggregation
in spinal cord motoneurons and muscle cells. In motoneurons, testosterone
triggers nuclear toxicity by inducing AR nuclear translocation. Thus, (i)
prevention of ARpolyQ nuclear localization, combined with (ii) an increased
ARpolyQ cytoplasmic clearance, should reduce its detrimental activity. Using the
antiandrogen Bicalutamide (Casodex((r))), which slows down AR activation and
nuclear translocation, and the disaccharide trehalose, an autophagy activator, we
found that, in motoneurons, the two compounds together reduced ARpolyQ insoluble
forms with higher efficiency than that obtained with single treatments. The
ARpolyQ clearance was mediated by trehalose-induced autophagy combined with the
longer cytoplasmic retention of ARpolyQ bound to Bicalutamide. This allows an
increased recognition of misfolded species by the autophagic system prior to
their migration into the nucleus. Interestingly, the combinatory use of trehalose
and Bicalutamide was also efficient in the removal of insoluble species of AR
with a very long polyQ (Q112) tract, which typically aggregates into the cell
nuclei. Collectively, these data suggest that the combinatory use of Bicalutamide
and trehalose is a novel approach to facilitate ARpolyQ clearance that has to be
tested in other cell types target of SBMA (i.e. muscle cells) and in vivo in
animal models of SBMA.
PMID- 25122661
TI - TDP-43 loss of cellular function through aggregation requires additional
structural determinants beyond its C-terminal Q/N prion-like domain.
AB - TDP-43 aggregates are the neurohistological landmark of diseases like amyotrophic
lateral sclerosis and frontotemporal dementia. Their role in the pathogenesis of
these conditions is not yet clear mainly due to the lack of proper models of
aggregation that may allow the study of the mechanism of formation, their
interactions with other cellular components and their effect on the cell
metabolism. In this work, we have used tandem repeats of the prion like Q/N-rich
region of TAR DNA-binding protein (TDP-43) fused to additional TDP-43 protein
sequences to trigger aggregate formation in neuronal and non-neuronal cell lines.
At the functional level, these aggregates are able to sequester endogenous TDP-43
depleting its nuclear levels and inducing loss of function at the pre-mRNA
splicing level. No apparent direct cellular toxicity of the aggregates seems to
be present beyond the lack of functional TDP-43. To our knowledge, this is the
only system that achieves full functional TDP 43 depletion with effects similar
to RNAi depletion or gene deletion. As a result, this model will prove useful to
investigate the loss-of-function effects mediated by TDP-43 aggregation within
cells without affecting the expression of the endogenous gene. We have identified
the N-terminus sequence of TDP-43 as the domain that enhances its interaction
with the aggregates and its insolubilization. These data show for the first time
that cellular TDP-43 aggregation can lead to total loss of function and to
defective splicing of TDP-43-dependent splicing events in endogenous genes.
PMID- 25122664
TI - Practice patterns and trends in the use of medical therapy in patients undergoing
percutaneous coronary intervention in Ontario.
AB - BACKGROUND: Clinical guidelines emphasize medical therapy as the initial approach
to the management of patients with stable coronary artery disease (CAD). However,
the extent to which medical therapy is applied before and after percutaneous
coronary intervention (PCI) in contemporary clinical practice is uncertain. We
evaluated medication use for patients with stable CAD undergoing PCI, and
assessed whether the COURAGE study altered medication use in the Canadian
healthcare system. METHODS AND RESULTS: A population-based cohort of 23 680 older
patients >65 years old) with stable CAD undergoing PCI in Ontario between 2003
and 2010 was assembled. Optimal medical therapy (OMT) was defined as prescription
for a beta-blocker, statin, and either angiotensin-converting enzyme inhibitor or
angiotensin II receptor blocker in the 90 days before PCI, and the same
medications plus thienopyridine 90 days following PCI. Prior to PCI, 8023 (33.9%)
patients were receiving OMT, 11 891 (50.2%) were on suboptimal therapy, and 3766
(15.9%) were not prescribed any medications of interest. There was significant
improvement in medical therapy following PCI (OMT: 11 149 [47.1%], suboptimal
therapy: 11 591 [48.9%], and none: 940 [4.0%], P<0.001). Utilization rate of OMT
reduced significantly after the publication of COURAGE (34.9% before versus 32.8%
after, P<0.001). Similarly, the rate of OMT following PCI was lower in the period
after publication of COURAGE (47.3% before versus 46.9% after, P<0.001).
CONCLUSIONS: OMT was prescribed in about 1 in 3 patients prior to PCI and less
than half after PCI. In contrast to the anticipated impact of COURAGE, we found
lower rates of medication use in PCI patients after its publication.
PMID- 25122662
TI - Genomic analysis of fibrolamellar hepatocellular carcinoma.
AB - Pediatric tumors are relatively infrequent, but are often associated with
significant lethality and lifelong morbidity. A major goal of pediatric cancer
research has been to identify key drivers of tumorigenesis to eventually develop
targeted therapies to enhance cure rate and minimize acute and long-term toxic
effects. Here, we used genomic approaches to identify biomarkers and candidate
drivers for fibrolamellar hepatocellular carcinoma (FL-HCC), a very rare subtype
of pediatric liver cancer for which limited therapeutic options exist. In-depth
genomic analyses of one tumor followed by immunohistochemistry validation on
seven other tumors showed expression of neuroendocrine markers in FL-HCC. DNA and
RNA sequencing data further showed that common cancer pathways are not visibly
altered in FL-HCC but identified two novel structural variants, both resulting in
fusion transcripts. The first, a 400 kb deletion, results in a DNAJB1-PRKCA
fusion transcript, which leads to increased cAMP-dependent protein kinase (PKA)
activity in the index tumor case and other FL-HCC cases compared with normal
liver. This PKA fusion protein is oncogenic in HCC cells. The second gene fusion
event, a translocation between the CLPTM1L and GLIS3 genes, generates a
transcript whose product also promotes cancer phenotypes in HCC cell lines. These
experiments further highlight the tumorigenic role of gene fusions in the
etiology of pediatric solid tumors and identify both candidate biomarkers and
possible therapeutic targets for this lethal pediatric disease.
PMID- 25122663
TI - Plasma phospholipid fatty acid biomarkers of dietary fat quality and endogenous
metabolism predict coronary heart disease risk: a nested case-control study
within the Women's Health Initiative observational study.
AB - BACKGROUND: Although the relationship between dietary fat quality and coronary
heart disease (CHD) risk has been evaluated, typically using diet questionnaires,
results are inconsistent and data in postmenopausal women are limited. Plasma
phospholipid fatty acid (PL-FA) profiles, reflecting dietary intake and
endogenous FA metabolism, may better predict diet-CHD risk. METHODS AND RESULTS:
Using a nested case-control design, we assessed the association between plasma PL
FA profiles and CHD risk in 2448 postmenopausal women (1224 cases with confirmed
CHD and 1224 controls matched for age, enrollment date, race/ethnicity, and
absence of CHD at baseline and after 4.5 years of follow-up) participating in the
Women's Health Initiative observational study. PL-FA profile was measured using
gas chromatography. Product/precursor ratios were used to estimate stearoyl-CoA
desaturase (16:1n-7/16:0, 18:1n-9/18:0), Delta6-desaturase (20:3n-6/18:2n-6), and
Delta5-desaturase (20:4n-6/20:3n-6) activities, indicators of endogenous FA
metabolism. Multivariate conditional logistic regression was used to obtain odds
ratios (95% CIs) for CHD risk. While no associations were observed for the
predominant PL fatty acid (16:0, 18:0, 18:1n-9, and 18:2n-6), plasma PL-saturated
fatty acid (1.20 [1.08 to 1.32]) and endogenously synthesized PL omega6 fatty
acids (20:3n-6; 3.22 [1.95 to 5.32]), 22:5n-6; 1.63 [1.20 to 2.23]) and Delta6
desaturase (1.25 [1.11 to 1.41]) were positively associated with CHD risk. PL
omega3 fatty acids (20:5n-3; 0.73 [0.58 to 0.93], 22:5n-3; 0.56 [0.33 to 0.94],
22:6n-3; 0.56 [0.39 to 0.80]), 18:1n-7 (0.54 [0.29 to 0.99]), and Delta5
desaturase (0.78 [0.70 to 0.88]) were inversely associated with CHD risk. Results
support current guidelines regarding regular fish consumption. Additional
findings include associations between endogenously synthesized fatty acids and
CHD risk, which were partly explained by changes in Delta6-desaturase and Delta5
desaturase indexes, suggesting that in vivo metabolism may also play an important
role in predicting CHD risk in this cohort of postmenopausal women. CLINICAL
TRIAL REGISTRATION URL: http://ClinicalTrials.gov, Unique identifier:
NCT01864122.
PMID- 25122665
TI - Choosing wisely for syncope: low-value carotid ultrasound use.
AB - BACKGROUND: The United States spends more than $750 billion annually on tests and
procedures that do not benefit patients. Although there is no physiological
indication for carotid ultrasound in "simple" syncope in the absence of focal
neurological signs or symptoms suggestive of stroke, there is concern that this
practice remains common for routine syncope workups. METHODS AND RESULTS: We used
a 5% random-sample Medicare claims database to evaluate large-scale national
trends in utilization of low-value carotid ultrasound imaging for simple syncope.
We found that 16.5% of all Medicare beneficiaries with simple syncope underwent
carotid imaging and 6.5% of all carotid ultrasounds ordered in 2009 were for this
low-value indication. These findings were complemented by a manual chart review
of 313 patients at a large academic medical center who underwent carotid
ultrasound for simple syncope over a 5-year period. For the 48 (15.4%) of 313
patients with stenosis >=50%, carotid ultrasound did not yield a causal
diagnosis. Only 2% of the 313 patients imaged experienced a change in medications
after a positive study, and <1% of patients underwent a carotid revascularization
procedure. CONCLUSIONS: These data suggest that carotid ultrasound for patients
with uncomplicated syncope are still commonly ordered and may be an easy target
for institutions striving to curtail low-value care.
PMID- 25122666
TI - Association of lower extremity performance with cardiovascular and all-cause
mortality in patients with peripheral artery disease: a systematic review and
meta-analysis.
AB - BACKGROUND: Peripheral artery disease (PAD) is associated with impaired mobility
and a high rate of mortality. The aim of this systematic review was to
investigate whether reduced lower extremity performance was associated with an
increased incidence of cardiovascular and all-cause mortality in people with PAD.
METHODS AND RESULTS: A systematic search of the MEDLINE, EMBASE, SCOPUS, Web of
Science, and Cochrane Library databases was conducted. Studies assessing the
association between measures of lower extremity performance and cardiovascular or
all-cause mortality in PAD patients were included. A meta-analysis was conducted
combining data from commonly assessed performance tests. The 10 identified
studies assessed lower extremity performance by strength tests, treadmill walking
performance, 6-minute walk, walking velocity, and walking impairment
questionnaire (WIQ). A meta-analysis revealed that shorter maximum walking
distance was associated with increased 5-year cardiovascular (unadjusted RR=2.54,
95% CI 1.86 to 3.47, P<10(-5), n=1577, fixed effects) and all-cause mortality
(unadjusted RR=2.23 95% CI 1.85 to 2.69, P<10(-5), n=1710, fixed effects). Slower
4-metre walking velocity, a lower WIQ stair-climbing score, and poor hip
extension, knee flexion, and plantar flexion strength were also associated with
increased mortality. No significant associations were found for hip flexion
strength, WIQ distance score, or WIQ speed score with mortality. CONCLUSIONS: A
number of lower extremity performance measures are prognostic markers for
mortality in PAD and may be useful clinical tools for identifying patients at
higher risk of death. Further studies are needed to determine whether
interventions that improve measures of lower extremity performance reduce
mortality.
PMID- 25122667
TI - Polymorphism identification and improved genome annotation of Brassica rapa
through Deep RNA sequencing.
AB - The mapping and functional analysis of quantitative traits in Brassica rapa can
be greatly improved with the availability of physically positioned, gene-based
genetic markers and accurate genome annotation. In this study, deep transcriptome
RNA sequencing (RNA-Seq) of Brassica rapa was undertaken with two objectives: SNP
detection and improved transcriptome annotation. We performed SNP detection on
two varieties that are parents of a mapping population to aid in development of a
marker system for this population and subsequent development of high-resolution
genetic map. An improved Brassica rapa transcriptome was constructed to detect
novel transcripts and to improve the current genome annotation. This is useful
for accurate mRNA abundance and detection of expression QTL (eQTLs) in mapping
populations. Deep RNA-Seq of two Brassica rapa genotypes-R500 (var. trilocularis,
Yellow Sarson) and IMB211 (a rapid cycling variety)-using eight different tissues
(root, internode, leaf, petiole, apical meristem, floral meristem, silique, and
seedling) grown across three different environments (growth chamber, greenhouse
and field) and under two different treatments (simulated sun and simulated shade)
generated 2.3 billion high-quality Illumina reads. A total of 330,995 SNPs were
identified in transcribed regions between the two genotypes with an average
frequency of one SNP in every 200 bases. The deep RNA-Seq reassembled Brassica
rapa transcriptome identified 44,239 protein-coding genes. Compared with current
gene models of B. rapa, we detected 3537 novel transcripts, 23,754 gene models
had structural modifications, and 3655 annotated proteins changed. Gaps in the
current genome assembly of B. rapa are highlighted by our identification of 780
unmapped transcripts. All the SNPs, annotations, and predicted transcripts can be
viewed at http://phytonetworks.ucdavis.edu/.
PMID- 25122669
TI - Evidence of hermaphroditism and sex ratio distortion in the fungal feeding
nematode Bursaphelenchus okinawaensis.
AB - Nematodes have many different reproductive strategies along with their divergent
life histories; the ability of hermaphrodite to self- and cross-fertilize is
useful for genetic manipulation. Here, we demonstrate the hermaphroditism of the
fungal feeding nematode Bursaphelenchus okinawaensis, which was formerly
described as a parthenogenetic nematode, and we show its other unique sexual
characteristics. To determine that it is hermaphroditic, we performed the
following experiments: observation of the pronuclear and chromosome behavior
during oogenesis and early embryogenesis; observation of spermatogenesis during
the fourth larval stage; investigation of sperm utilization; and investigation of
phenotypic segregation after cross-mating using a chemically induced visible
mutant. We then investigated the mating preferences and spermatid size difference
between males and hermaphrodites. B. okinawaensis males successfully mated only
with sperm-depleted old hermaphrodites, and the spermatid sizes of males were
almost the same as those of hermaphrodites. Moreover, the sex ratio of cross
fertilized progeny was highly skewed toward hermaphrodites. B. okinawaensis is
phylogenetically distant from established model nematodes such as C. elegans and
is more closely related to some economically relevant parasitic nematodes. This
newly discovered hermaphroditic nematode has great potential for evolutionary and
parasitological research.
PMID- 25122668
TI - Genome-wide linkage disequilibrium in nine-spined stickleback populations.
AB - Variation in the extent and magnitude of genome-wide linkage disequilibrium (LD)
among populations residing in different habitats has seldom been studied in wild
vertebrates. We used a total of 109 microsatellite markers to quantify the level
and patterns of genome-wide LD in 13 Fennoscandian nine-spined stickleback
(Pungitius pungitius) populations from four (viz. marine, lake, pond, and river)
different habitat types. In general, high magnitude (D' > 0.5) of LD was found
both in freshwater and marine populations, and the magnitude of LD was
significantly greater in inland freshwater than in marine populations.
Interestingly, three coastal freshwater populations located in close geographic
proximity to the marine populations exhibited similar LD patterns and genetic
diversity as their marine neighbors. The greater levels of LD in inland
freshwater compared with marine and costal freshwater populations can be
explained in terms of their contrasting demographic histories: founder events,
long-term isolation, small effective sizes, and population bottlenecks are
factors likely to have contributed to the high levels of LD in the inland
freshwater populations. In general, these findings shed new light on the patterns
and extent of variation in genome-wide LD, as well as the ecological and
evolutionary factors driving them.
PMID- 25122670
TI - Distinct and predictive histone lysine acetylation patterns at promoters,
enhancers, and gene bodies.
AB - In eukaryotic cells, histone lysines are frequently acetylated. However, unlike
modifications such as methylations, histone acetylation modifications are often
considered redundant. As such, the functional roles of distinct histone
acetylations are largely unexplored. We previously developed an algorithm RFECS
to discover the most informative modifications associated with the classification
or prediction of mammalian enhancers. Here, we used this tool to identify the
modifications most predictive of promoters, enhancers, and gene bodies.
Unexpectedly, we found that histone acetylation alone performs well in
distinguishing these unique genomic regions. Further, we found the association of
characteristic acetylation patterns with genic regions and association of
chromatin state with splicing. Taken together, our work underscores the diverse
functional roles of histone acetylation in gene regulation and provides several
testable hypotheses to dissect these roles.
PMID- 25122672
TI - The health effects of employment.
PMID- 25122671
TI - Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of
imatinib: a randomized controlled open-label trial.
AB - BACKGROUND: Masitinib is a highly selective tyrosine kinase inhibitor with
activity against the main oncogenic drivers of gastrointestinal stromal tumor
(GIST). Masitinib was evaluated in patients with advanced GIST after imatinib
failure or intolerance. PATIENTS AND METHODS: Prospective, multicenter,
randomized, open-label trial. Patients with inoperable, advanced imatinib
resistant GIST were randomized (1 : 1) to receive masitinib (12 mg/kg/day) or
sunitinib (50 mg/day 4-weeks-on/2-weeks-off) until progression, intolerance, or
refusal. Primary efficacy analysis was noncomparative, testing whether masitinib
attained a median progression-free survival (PFS) (blind centrally reviewed
RECIST) threshold of >3 months according to the lower bound of the 90% unilateral
confidence interval (CI). Secondary analyses on overall survival (OS) and PFS
were comparative with results presented according to a two-sided 95% CI. RESULTS:
Forty-four patients were randomized to receive masitinib (n = 23) or sunitinib (n
= 21). Median follow-up was 14 months. Patients receiving masitinib experienced
less toxicity than those receiving sunitinib, with significantly lower occurrence
of severe adverse events (52% versus 91%, respectively, P = 0.008). Median PFS
(central RECIST) for the noncomparative primary analysis in the masitinib
treatment arm was 3.71 months (90% CI 3.65). Secondary analyses showed that
median OS was significantly longer for patients receiving masitinib followed by
post-progression addition of sunitinib when compared against patients treated
directly with sunitinib in second-line [hazard ratio (HR) = 0.27, 95% CI 0.09
0.85, P = 0.016]. This improvement was sustainable as evidenced by 26-month
follow-up OS data (HR = 0.40, 95% CI 0.16-0.96, P = 0.033); an additional 12.4
months survival advantage being reported for the masitinib treatment arm. Risk of
progression while under treatment with masitinib was in the same range as for
sunitinib (HR = 1.1, 95% CI 0.6-2.2, P = 0.833). CONCLUSIONS: Primary efficacy
analysis ensured the masitinib treatment arm could satisfy a prespecified PFS
threshold. Secondary efficacy analysis showed that masitinib followed by the
standard of care generated a statistically significant survival benefit over
standard of care. Encouraging median OS and safety data from this well-controlled
and appropriately designed randomized trial indicate a positive benefit-risk
ratio. Further development of masitinib in imatinib-resistant/intolerant patients
with advanced GIST is warranted.
PMID- 25122674
TI - Clovis at the end of the world.
PMID- 25122675
TI - Plasmonic nanoparticle scattering for color holograms.
AB - This work presents an original approach to create holograms based on the optical
scattering of plasmonic nanoparticles. By analogy to the diffraction produced by
the scattering of atoms in X-ray crystallography, we show that plasmonic
nanoparticles can produce a wave-front reconstruction when they are sampled on a
diffractive plane. By applying this method, all of the scattering characteristics
of the nanoparticles are transferred to the reconstructed field. Hence, we
demonstrate that a narrow-band reconstruction can be achieved for direct white
light illumination on an array of plasmonic nanoparticles. Furthermore,
multicolor capabilities are shown with minimal cross-talk by multiplexing
different plasmonic nanoparticles at subwavelength distances. The holograms were
fabricated from a single subwavelength thin film of silver and demonstrate that
the total amount of binary information stored in the plane can exceed the limits
of diffraction and that this wavelength modulation can be detected optically in
the far field.
PMID- 25122676
TI - Pharmacological chaperones in the age of proteomic pathology.
PMID- 25122673
TI - Calcineurin determines toxic versus beneficial responses to alpha-synuclein.
AB - Calcineurin (CN) is a highly conserved Ca(2+)-calmodulin (CaM)-dependent
phosphatase that senses Ca(2+) concentrations and transduces that information
into cellular responses. Ca(2+) homeostasis is disrupted by alpha-synuclein
(alpha-syn), a small lipid binding protein whose misfolding and accumulation is a
pathological hallmark of several neurodegenerative diseases. We report that alpha
syn, from yeast to neurons, leads to sustained highly elevated levels of
cytoplasmic Ca(2+), thereby activating a CaM-CN cascade that engages substrates
that result in toxicity. Surprisingly, complete inhibition of CN also results in
toxicity. Limiting the availability of CaM shifts CN's spectrum of substrates
toward protective pathways. Modulating CN or CN's substrates with highly
selective genetic and pharmacological tools (FK506) does the same. FK506 crosses
the blood brain barrier, is well tolerated in humans, and is active in neurons
and glia. Thus, a tunable response to CN, which has been conserved for a billion
years, can be targeted to rebalance the phosphatase's activities from toxic
toward beneficial substrates. These findings have immediate therapeutic
implications for synucleinopathies.
PMID- 25122678
TI - Reconsidering the phylogenetic utility of miRNA in animals.
PMID- 25122677
TI - Genetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers
thyroid autoimmunity.
AB - Graves disease (GD) is an autoimmune condition caused by interacting genetic and
environmental factors. Genetic studies have mapped several single-nucleotide
polymorphisms (SNPs) that are strongly associated with GD, but the mechanisms by
which they trigger disease are unknown. We hypothesized that epigenetic
modifications induced by microenvironmental influences of cytokines can reveal
the functionality of GD-associated SNPs. We analyzed genome-wide histone H3
lysine 4 methylation and gene expression in thyroid cells induced by IFNalpha, a
key cytokine secreted during viral infections, and overlapped them with known GD
associated SNPs. We mapped an open chromatin region overlapping two adjacent GD
associated SNPs (rs12101255 and rs12101261) in intron 1 of the thyroid
stimulating hormone receptor (TSHR) gene. We then demonstrated that this region
functions as a regulatory element through binding of the transcriptional
repressor promyelocytic leukemia zinc finger protein (PLZF) at the rs12101261
site. Repression by PLZF depended on the rs12101261 disease susceptibility allele
and was increased by IFNalpha. Intrathymic TSHR expression was decreased in
individuals homozygous for the rs12101261 disease-associated genotype compared
with carriers of the disease-protective allele. Our studies discovered a genetic
epigenetic interaction involving a noncoding SNP in the TSHR gene that regulates
thymic TSHR gene expression and facilitates escape of TSHR-reactive T cells from
central tolerance, triggering GD.
PMID- 25122680
TI - Intraoperative cell-cycle analysis to guide brain tumor removal.
PMID- 25122679
TI - Arginine starvation-associated atypical cellular death involves mitochondrial
dysfunction, nuclear DNA leakage, and chromatin autophagy.
AB - Autophagy is the principal catabolic prosurvival pathway during nutritional
starvation. However, excessive autophagy could be cytotoxic, contributing to cell
death, but its mechanism remains elusive. Arginine starvation has emerged as a
potential therapy for several types of cancers, owing to their tumor-selective
deficiency of the arginine metabolism. We demonstrated here that arginine
depletion by arginine deiminase induces a cytotoxic autophagy in
argininosuccinate synthetase (ASS1)-deficient prostate cancer cells. Advanced
microscopic analyses of arginine-deprived dying cells revealed a novel phenotype
with giant autophagosome formation, nucleus membrane rupture, and histone
associated DNA leakage encaptured by autophagosomes, which we shall refer to as
chromatin autophagy, or chromatophagy. In addition, nuclear inner membrane (lamin
A/C) underwent localized rearrangement and outer membrane (NUP98) partially fused
with autophagosome membrane. Further analysis showed that prolonged arginine
depletion impaired mitochondrial oxidative phosphorylation function and
depolarized mitochondrial membrane potential. Thus, reactive oxygen species (ROS)
production significantly increased in both cytosolic and mitochondrial fractions,
presumably leading to DNA damage accumulation. Addition of ROS scavenger N-acetyl
cysteine or knockdown of ATG5 or BECLIN1 attenuated the chromatophagy phenotype.
Our data uncover an atypical autophagy-related death pathway and suggest that
mitochondrial damage is central to linking arginine starvation and chromatophagy
in two distinct cellular compartments.
PMID- 25122681
TI - A sequence-specific transcription activator motif and powerful synthetic variants
that bind Mediator using a fuzzy protein interface.
AB - Although many transcription activators contact the same set of coactivator
complexes, the mechanism and specificity of these interactions have been unclear.
For example, do intrinsically disordered transcription activation domains (ADs)
use sequence-specific motifs, or do ADs of seemingly different sequence have
common properties that encode activation function? We find that the central
activation domain (cAD) of the yeast activator Gcn4 functions through a short,
conserved sequence-specific motif. Optimizing the residues surrounding this short
motif by inserting additional hydrophobic residues creates very powerful ADs that
bind the Mediator subunit Gal11/Med15 with high affinity via a "fuzzy" protein
interface. In contrast to Gcn4, the activity of these synthetic ADs is not
strongly dependent on any one residue of the AD, and this redundancy is similar
to that of some natural ADs in which few if any sequence-specific residues have
been identified. The additional hydrophobic residues in the synthetic ADs likely
allow multiple faces of the AD helix to interact with the Gal11 activator-binding
domain, effectively forming a fuzzier interface than that of the wild-type cAD.
PMID- 25122683
TI - No evidence for sample contamination or diet offset for pre-Columbian chicken
dates from El Arenal.
PMID- 25122682
TI - Hampered long-term depression and thin spine loss in the nucleus accumbens of
ethanol-dependent rats.
AB - Alcoholism involves long-term cognitive deficits, including memory impairment,
resulting in substantial cost to society. Neuronal refinement and stabilization
are hypothesized to confer resilience to poor decision making and addictive-like
behaviors, such as excessive ethanol drinking and dependence. Accordingly,
structural abnormalities are likely to contribute to synaptic dysfunctions that
occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we
show that ethanol-dependent rats display a loss of dendritic spines in medium
spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction
of tyrosine hydroxylase immunostaining and postsynaptic density 95-positive
elements. Further analysis indicates that "long thin" but not "mushroom" spines
are selectively affected. In addition, patch-clamp experiments from Nacc slices
reveal that long-term depression (LTD) formation is hampered, with parallel
changes in field potential recordings and reductions in NMDA-mediated synaptic
currents. These changes are restricted to the withdrawal phase of ethanol
dependence, suggesting their relevance in the genesis of signs and/or symptoms
affecting ethanol withdrawal and thus the whole addictive cycle. Overall, these
results highlight the key role of dynamic alterations in dendritic spines and
their presynaptic afferents in the evolution of alcohol dependence. Furthermore,
they suggest that the selective loss of long thin spines together with a reduced
NMDA receptor function may affect learning. Disruption of this LTD could
contribute to the rigid emotional and motivational state observed in alcohol
dependence.
PMID- 25122685
TI - Statistical flaws undermine pre-Columbian chicken debate.
PMID- 25122684
TI - No evidence against Polynesian dispersal of chickens to pre-Columbian South
America.
PMID- 25122686
TI - A Site-Specific Integrated Col2.3GFP Reporter Identifies Osteoblasts Within
Mineralized Tissue Formed In Vivo by Human Embryonic Stem Cells.
AB - The use of human embryonic stem cells (hESCs) and induced pluripotent stem cells
(iPSCs) for study and treatment of bone diseases or traumatic bone injuries
requires efficient protocols to differentiate hESCs/iPSCs into cells with
osteogenic potential and the ability to isolate differentiated osteoblasts for
analysis. We have used zinc finger nuclease technology to deliver a construct
containing the Col2.3 promoter driving GFPemerald to the AAVS1 site (referred to
as a "safe harbor" site), in human embryonic stem cells (H9Zn2.3GFP), with the
goal of marking the cells that have become differentiated osteoblasts. In
teratomas formed using these cells, we identified green fluorescent protein (GFP)
positive cells specifically associated with in vivo bone formation. We also
differentiated the cells into a mesenchymal stem cell population with osteogenic
potential and implanted them into a mouse calvarial defect model. We observed GFP
positive cells associated with alizarin complexone-labeled newly formed bone
surfaces. The cells were alkaline phosphatase-positive, and immunohistochemistry
with human specific bone sialoprotein (BSP) antibody indicates that the GFP
positive cells are also associated with the human BSP-containing matrix,
demonstrating that the Col2.3GFP construct marks cells in the osteoblast lineage.
Single-cell cloning generated a 100% Col2.3GFP-positive cell population, as
demonstrated by fluorescence in situ hybridization using a GFP probe. The
karyotype was normal, and pluripotency was demonstrated by Tra1-60
immunostaining, pluripotent low density reverse transcription-polymerase chain
reaction array and embryoid body formation. These cells will be useful to develop
optimal osteogenic differentiation protocols and to isolate osteoblasts from
normal and diseased iPSCs for analysis.
PMID- 25122687
TI - Are all cancer stem cells created equal?
AB - Numerous solid malignancies have been reported to contain cancer stem cells
(CSCs). Distinct functional characteristics have been attributed to CSCs, and
thus it is widely believed that these unique cells may have genetic and
phenotypic homogeneity. Recent exciting but limited evidence, however,
contradicts this tenet and supports the intriguing concept of genetic and
phenotypic diversity in the CSC population. We propose that CSC heterogeneity at
the inter- and intrapatient levels may be due to the cell of origin, to
environmental cues, and/or to human papillomavirus infection. Additional insight
into CSC heterogeneity is needed to identify actionable targets for optimal
eradication of the diverse CSC subpopulations within a tumor.
PMID- 25122688
TI - Longitudinal Analysis of DNA Methylation in CD34+ Hematopoietic Progenitors in
Myelodysplastic Syndrome.
AB - Myelodysplastic syndrome (MDS) is a disorder of hematopoietic stem cells (HSCs)
that is often treated with DNA methyltransferase 1 (DNMT1) inhibitors (5
azacytidine [AZA], 5-aza-2'-deoxycytidine), suggesting a role for DNA methylation
in disease progression. How DNMT inhibition retards disease progression and how
DNA methylation contributes to MDS remain unclear. We analyzed global DNA
methylation in purified CD34+ hematopoietic progenitors from MDS patients
undergoing multiple rounds of AZA treatment. Differential methylation between MDS
phenotypes was observed primarily at developmental regulators not expressed
within the hematopoietic compartment and was distinct from that observed between
healthy hematopoietic cell types. After AZA treatment, we observed only limited
DNA demethylation at sites that varied between patients. This suggests that a
subset of the stem cell population is resistant to AZA and provides a basis for
disease relapse. Using gene expression data from patient samples and an in vitro
AZA treatment study, we identified differentially methylated genes that can be
activated following treatment and that remain silent in the CD34+ stem cell
compartment of high-risk MDS patients. Haploinsufficiency in mice of one of these
genes (NR4A2) has been shown to lead to excessive HSC proliferation, and our data
suggest that suppression of NR4A2 by DNA methylation may be involved in MDS
progression.
PMID- 25122692
TI - Type of homogenization and fat loss during continuous infusion of human milk.
AB - BACKGROUND: Substantial fat loss may occur during continuous feeding of human
milk (HM). A decrease of fat loss has been described following homogenization.
Well-established methods of homogenization of HM for routine use in the neonatal
intensive care unit (NICU) would be desirable. OBJECTIVE: We compared the loss of
fat based on the use of 3 different methods for homogenizing thawed HM during
continuous feeding. METHODS: Sixteen frozen donor HM samples were thawed,
homogenized with ultrasound and separated into 3 aliquots ("baseline agitation,"
"hourly agitation," and "ultrasound"), and then frozen for 48 hours. Aliquots
were thawed again and a baseline agitation was applied. Subsequently, aliquots
baseline agitation and hourly agitation were drawn into a syringe, while
ultrasound was applied to aliquot ultrasound before it was drawn into a syringe.
The syringes were loaded into a pump (2 mL/h; 4 hours). At hourly intervals the
hourly agitation infusion was stopped, the syringe was disconnected and gently
shaken. During infusion, samples from the 3 groups were collected hourly for
analysis of fat and caloric content. RESULTS: The 3 groups of homogenization
showed similar fat content at the beginning of the infusion. For fat, mean (SD)
hourly changes of -0.03 (0.01), -0.09 (0.01), and -0.09 (0.01) g/dL were observed
for the hourly agitation, baseline agitation, and ultrasound groups,
respectively. The decrease was smaller for the hourly agitation group (P < .001).
CONCLUSION: When thawed HM is continuously infused, a smaller fat loss is
observed when syringes are agitated hourly versus when ultrasound or a baseline
homogenization is used.
PMID- 25122691
TI - Concise review: dedifferentiation meets cancer development: proof of concept for
epigenetic cancer.
AB - The technology for generation of induced pluripotent stem cells (iPSCs) has made
significant contributions to various scientific fields, and the field of cancer
biology is no exception. Although cancer is generally believed to develop through
accumulation of multiple genetic mutations, there is increasing evidence that
cancer cells also acquire epigenetic abnormalities during development,
maintenance, and progression. Because the epigenetic status of somatic cells
changes dynamically through reprogramming, iPSC technology can be utilized to
actively and globally alter the epigenetic status of differentiated cells. Using
this technology, a recent study has revealed that some types of cancer can
develop mainly through disruption of the epigenetic status triggered by
dedifferentiation. In this paper, we outline the reprograming process and the
epigenetic mechanism associated with the maintenance or conversion of cell
identity. We then describe several observations suggesting that dedifferentiation
can play an important role in cancer development. Finally, we introduce the
system responsible for in vivo reprogramming to demonstrate the involvement of
dedifferentiation-driven epigenetic disruption in cancer development, and propose
that particular types of cancer can develop predominantly through epigenetic
alterations.
PMID- 25122690
TI - Cost-effective master cell bank validation of multiple clinical-grade human
pluripotent stem cell lines from a single donor.
AB - Standardization guidelines for human pluripotent stem cells are still very
broadly defined, despite ongoing clinical trials in the U.S., U.K., and Japan.
The requirements for validation of human embryonic (hESCs) and induced
pluripotent stem cells (iPSCs) in general follow the regulations for other
clinically compliant biologics already in place but without addressing key
differences between cell types or final products. In order to realize the full
potential of stem cell therapy, validation criteria, methodology, and, most
importantly, strategy, should address the shortfalls and efficiency of current
approaches; without this, hESC- and, especially, iPSC-based therapy will not be
able to compete with other technologies in a cost-efficient way. We addressed the
protocols for testing cell lines for human viral pathogens and propose a novel
strategy that would significantly reduce costs. It is highly unlikely that the
multiple cell lines derived in parallel from a tissue sample taken from one donor
would have different profiles of endogenous viral pathogens; we therefore argue
that samples from the Master Cell Banks of sibling lines could be safely pooled
for validation. We illustrate this approach with tiered validation of two sibling
clinical-grade hESC lines, KCL033 and KCL034 (stage 1, sterility; stage 2,
specific human pathogens; and stage 3, nonspecific human pathogens). The results
of all tests were negative. This cost-effective strategy could also be applied
for validation of Master Cell Banks of multiple clinical-grade iPSC lines derived
from a single donor.
PMID- 25122689
TI - Different culture conditions modulate the immunological properties of adipose
stem cells.
AB - The potential of human adipose stem cells (ASCs) for regenerative medicine has
received recognition owing to their ease of isolation and their multilineage
differentiation capacity. Additionally, low immunogenicity and immunosuppressive
properties make them a relevant cell source when considering immunomodulation
therapies and allogeneic stem cell treatments. In the current study,
immunogenicity and immunosuppression of ASCs were determined through mixed
lymphocyte reactions. The immunogenic response was analyzed after cell isolation
and expansion in fetal bovine serum (FBS), human serum (HS)-supplemented medium,
and xeno-free and serum-free (XF/SF) conditions. Additionally, the
immunophenotype and the secretion of CXC chemokine ligand 8 (CXCL8), CXCL9,
CXCL10, C-C chemokine ligand 2 (CCL2), CCL5, interleukin 2 (IL-2), IL-4, IL-6, IL
10, IL-17A, tumor necrosis factor-alpha, interferon-gamma, transforming growth
factor-beta1, indoleamine 2,3-deoxygenase, Galectin-1, and Galectin-3 were
analyzed. The results showed that ASCs were weakly immunogenic when expanded in
any of the three conditions. The significantly strongest suppression was observed
with cells expanded in FBS conditions, whereas higher ASC numbers were required
to display suppression in HS or XF/SF conditions. In addition, statistically
significant differences in protein secretion were observed between direct versus
indirect cocultures and between different culture conditions. The characteristic
immunophenotype of ASCs was maintained in all conditions. However, in XF/SF
conditions, a significantly lower expression of CD54 (intercellular adhesion
molecule 1) and a higher expression of CD45 (lymphocyte common antigen) was
observed at a low passage number. Although culture conditions have an effect on
the immunogenicity, immunosuppression, and protein secretion profile of ASCs, our
findings demonstrated that ASCs have low immunogenicity and promising
immunosuppressive potential whether cultured in FBS, HS, or XF/SF conditions.
PMID- 25122693
TI - Pathological response and safety of two neoadjuvant strategies with bevacizumab
in MRI-defined locally advanced T3 resectable rectal cancer: a randomized,
noncomparative phase II study.
AB - BACKGROUND: In T3 rectal cancer (RC), preoperative chemoradiotherapy [5
fluorouracil (5-FU-RT)] reduces local recurrences, but does not affect overall
survival. New therapeutic options are still necessary to improve clinical
outcomes. PATIENTS AND METHODS: This randomized, noncomparative, open-label,
multicenter, two arms, phase II study was conducted in MRI-defined locally
advanced T3 resectable RC. In arm A, patients received 12-week bevacizumab plus 5
FU, leucovorin and oxaliplatin (Folfox-4) followed with bevacizumab-5-FU-RT
before total mesorectal excision (TME). In arm B, patients received only
bevacizumab-5-FU-RT before TME. Primary end point was pathological complete
response (pCR) rate. RESULTS: Forty-six patients were randomized in arm A and 45
patients in arm B. In arm A, the rate of pCR was 23.8% [95% confidence interval
(CI) 12.1% to 39.5%] statistically superior to the defined standard rate of 10%,
P = 0.015. In arm B, the rate of pCR of 11.4% (95% CI 3.8% to 24.6%) was not
different from 10%, P = 0.906. No death occurred during the study period, from
the start until 8 weeks following surgery. Postoperative fistulas were reported
for 16 patients (7 in arm A and 9 in arm B). CONCLUSION: Even if the addition of
bevacizumab induced manageable toxicities including an increased risk of
postoperative fistula and no treatment-related death, arm B did not achieve the
expected pCR rate in the population of patients included. Induction bevacizumab
Folfox-4 followed by bevacizumab-5-FU-RT is promising. It is however necessary to
continue investigations in the management of locally advanced RC.
ClinicalTrials.gov Identifier: NCT 00865189.
PMID- 25122694
TI - Second-line chemotherapy in advanced biliary cancer: the present now will later
be past.
PMID- 25122695
TI - Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice
Guidelines for diagnosis, treatment and follow-up.
PMID- 25122698
TI - SILARS: an effective stable isotope labeling with ammonium nitrate-15N in rice
seedlings for quantitative proteomic analysis.
PMID- 25122699
TI - A novel single-nucleotide mutation in a CLAVATA3 gene homolog controls a
multilocular silique trait in Brassica rapa L.
PMID- 25122696
TI - Combinatorial complexity in a transcriptionally centered signaling hub in
Arabidopsis.
AB - A subfamily of four Phytochrome (phy)-Interacting bHLH transcription Factors
(PIFs) collectively promote skotomorphogenic development in dark-grown seedlings.
This activity is reversed upon exposure to light, by photoactivated phy molecules
that induce degradation of the PIFs, thereby triggering the transcriptional
changes that drive a transition to photomorphogenesis. The PIFs function both
redundantly and partially differentially at the morphogenic level in this
process. To identify the direct targets of PIF transcriptional regulation genome
wide, we analyzed the DNA-binding sites for all four PIFs by ChIP-seq analysis,
and defined the genes transcriptionally regulated by each PIF, using RNA-seq
analysis of pif mutants. Despite the absence of detectable differences in DNA
binding-motif recognition between the PIFs, the data show a spectrum of
regulatory patterns, ranging from single PIF dominance to equal contributions by
all four. Similarly, a broad array of promoter architectures was found, ranging
from single PIF-binding sites, containing single sequence motifs, through
multiple PIF-binding sites, each containing one or more motifs, with each site
occupied preferentially by one to multiple PIFs. Quantitative analysis of the
promoter occupancy and expression level induced by each PIF revealed an
intriguing pattern. Although there is no robust correlation broadly across the
target-gene population, examination of individual genes that are shared targets
of multiple PIFs shows a gradation in correlation from strongly positive, through
uncorrelated, to negative. This finding suggests a dual-layered mechanism of
transcriptional regulation, comprising both a continuum of binding-site occupancy
by each PIF and a superimposed layer of local regulation that acts differentially
on each PIF, to modulate its intrinsic transcriptional activation capacity at
each site, in a quantitative pattern that varies between the individual PIFs from
gene to gene. These findings provide a framework for probing the mechanisms by
which transcription factors with overlapping direct-target genes integrate and
selectively transduce signals to their target networks.
PMID- 25122697
TI - MADS-box transcription factor AGL21 regulates lateral root development and
responds to multiple external and physiological signals.
AB - Plant root system morphology is dramatically influenced by various environmental
cues. The adaptation of root system architecture to environmental constraints,
which mostly depends on the formation and growth of lateral roots, is an
important agronomic trait. Lateral root development is regulated by the external
signals coordinating closely with intrinsic signaling pathways. MADS-box
transcription factors are known key regulators of the transition to flowering and
flower development. However, their functions in root development are still poorly
understood. Here we report that AGL21, an AGL17-clade MADS-box gene, plays a
crucial role in lateral root development. AGL21 was highly expressed in root,
particularly in the root central cylinder and lateral root primordia. AGL21
overexpression plants produced more and longer lateral roots while agl21 mutants
showed impaired lateral root development, especially under nitrogen-deficient
conditions. AGL21 was induced by many plant hormones and environmental stresses,
suggesting a function of this gene in root system plasticity in response to
various signals. Furthermore, AGL21 was found positively regulating auxin
accumulation in lateral root primordia and lateral roots by enhancing local auxin
biosynthesis, thus stimulating lateral root initiation and growth. We propose
that AGL21 may be involved in various environmental and physiological signals
mediated lateral root development and growth.
PMID- 25122700
TI - Oculomotor task switching: alternating from a nonstandard to a standard response
yields the unidirectional prosaccade switch-cost.
AB - The completion of an antisaccade (i.e., a nonstandard task) lengthens the
reaction time (RT) of a subsequent prosaccade: a behavioral phenomenon termed the
unidirectional prosaccade switch-cost. One explanation for the unidirectional
prosaccade switch-cost is suppressing a stimulus-driven prosaccade during the
preceding antisaccade trial engenders a residual inhibition of the oculomotor
networks that support prosaccade planning (i.e., the oculomotor inhibition
hypothesis). Alternatively, the unidirectional prosaccade switch-cost may reflect
the persistent activation of the antisaccade's nonstandard task rules (i.e., task
set), which delays the planning of the next prosaccade (i.e., task-set inertia
hypothesis). To determine which hypothesis provides the most parsimonious account
for the unidirectional prosaccade switch-cost, participants alternated between
pro- and antisaccades wherein task instructions (i.e., pro- and antisaccade) were
provided before (i.e., classic cuing) or concurrent (i.e., delayed cuing) with
response cuing. Importantly, pro- and antisaccades elicited via the delayed cuing
condition required the suppression of a stimulus-driven prosaccade at response
cuing (i.e., response suppression) to discern the appropriate to-be-performed
task. Results showed that classic and delayed antisaccades, but not delayed
prosaccades, lengthened the RT of subsequent prosaccades. That delayed
prosaccades, which require response suppression for their successful execution,
did not lengthen the RT of subsequent prosaccades indicates that the oculomotor
inhibition hypothesis does not account for the unidirectional prosaccade switch
cost. Instead, the current findings are in line with the assertion that the task
set associated with a nonstandard antisaccade persists inertially and delays the
planning of a subsequent prosaccade (i.e., task-set inertia hypothesis).
PMID- 25122701
TI - Role of spinal bombesin-responsive neurons in nonhistaminergic itch.
AB - Intrathecal administration of the neurotoxin bombesin-saporin reduces or
abolishes pruritogen-evoked scratching behavior. We investigated whether spinal
neurons that respond to intradermal (ID) injection of pruritogens also respond to
spinal superfusion of bombesin and vice versa. Single-unit recordings were made
from superficial lumbar spinal dorsal horn neurons in anesthetized mice. We
identified neurons with three search strategies: 1) ID injection of the
nonhistaminergic itch mediator chloroquine, 2) spinal superfusion of bombesin,
and 3) noxious pinch. All units were tested with an array of itch mediators
(chloroquine, histamine, SLIGRL, BAM8-22), algogens [capsaicin, allyl
isothiocyanate (AITC)], and physical stimuli (brush, pinch, noxious heat,
cooling) applied to the hindlimb receptive field. The vast majority of
chloroquine-responsive units also responded to bombesin. Of 26 chloroquine
sensitive units tested, most responded to SLIGRL, half responded to histamine
and/or BAM8-22, and most responded to capsaicin and/or AITC as well as noxious
thermal and mechanical stimuli. Of 29 bombesin-responsive units, a large majority
also responded to other itch mediators as well as AITC, capsaicin, and noxious
thermal and mechanical stimuli. Responses to successive applications of bombesin
exhibited tachyphylaxis. In contrast, of 36 units responsive to noxious pinch,
the majority (67%) did not respond to ID chloroquine or spinal bombesin. It is
suggested that chloroquine- and bombesin-sensitive spinal neurons signal itch
from the skin.
PMID- 25122703
TI - Radial-tangential anisotropy of crowding in the early visual areas.
AB - Crowding, the inability to recognize an individual object in clutter (Bouma H.
Nature 226: 177-178, 1970), is considered a major impediment to object
recognition in peripheral vision. Despite its significance, the cortical loci of
crowding are not well understood. In particular, the role of the primary visual
cortex (V1) remains unclear. Here we utilize a diagnostic feature of crowding to
identify the earliest cortical locus of crowding. Controlling for other factors,
radially arranged flankers induce more crowding than tangentially arranged ones
(Toet A, Levi DM. Vision Res 32: 1349-1357, 1992). We used functional magnetic
resonance imaging (fMRI) to measure the change in mean blood oxygenation level
dependent (BOLD) response due to the addition of a middle letter between a pair
of radially or tangentially arranged flankers. Consistent with the previous
finding that crowding is associated with a reduced BOLD response [Millin R, Arman
AC, Chung ST, Tjan BS. Cereb Cortex (July 5, 2013). doi:10.1093/cercor/bht159],
we found that the BOLD signal evoked by the middle letter depended on the
arrangement of the flankers: less BOLD response was associated with adding the
middle letter between radially arranged flankers compared with adding it between
tangentially arranged flankers. This anisotropy in BOLD response was present as
early as V1 and remained significant in downstream areas. The effect was observed
while subjects' attention was diverted away from the testing stimuli. Contrast
detection threshold for the middle letter was unaffected by flanker arrangement,
ruling out surround suppression of contrast response as a major factor in the
observed BOLD anisotropy. Our findings support the view that V1 contributes to
crowding.
PMID- 25122702
TI - Adaptation of high-gamma responses in human auditory association cortex.
AB - This study investigates adaptation of high-frequency cortical responses [>60 Hz;
high-gamma (HG)] to simple and complex sounds in human nonprimary auditory
cortex. We used intracranial electrocorticographic recordings to measure event
related changes in HG power as a function of stimulus probability. Tone and
speech stimuli were presented in a series of traditional oddball and control
paradigms. We hypothesized that HG power attenuates with stimulus repetition over
multiple concurrent time scales in auditory association cortex. Time-frequency
analyses were performed to identify auditory-responsive sites. Single-trial
analyses and quantitative modeling were then used to measure trial-to-trial
changes in HG power for high (frequent), low (infrequent), and equal (control)
stimulus probabilities. Results show strong reduction of HG responses to
frequently repeated tones and speech, with no differences in responses to
infrequent and equal-probability stimuli. Adaptation of the HG frequent response,
and not stimulus-acoustic differences or deviance-detection enhancement effects,
accounted for the differential responses observed for frequent and infrequent
sounds. Adaptation of HG responses showed a rapid onset (less than two trials)
with slower adaptation between consecutive, repeated trials (2-10 s) and across
trials in a stimulus block (~7 min). The auditory-evoked N100 response also
showed repetition-related adaptation, consistent with previous human scalp and
animal single-unit recordings. These findings indicate that HG responses are
highly sensitive to the regularities of simple and complex auditory events and
show adaptation on multiple concurrent time scales in human auditory association
cortex.
PMID- 25122705
TI - Analysis of the long-term actions of gabapentin and pregabalin in dorsal root
ganglia and substantia gelatinosa.
AB - The alpha2delta-ligands pregabalin (PGB) and gabapentin (GBP) are used to treat
neuropathic pain. We used whole cell recording to study their long-term effects
on substantia gelatinosa and dorsal root ganglion (DRG) neurons. Spinal cord
slices were prepared from embryonic day 13 rat embryos and maintained in
organotypic culture for >5 wk (neuronal age equivalent to young adult rats).
Exposure of similarly aged DRG neurons (dissociated and cultured from postnatal
day 19 rats) to GBP or PGB for 5-6 days attenuated high-voltage-activated calcium
channel currents (HVA ICa). Strong effects were seen in medium-sized and in small
isolectin B4-negative (IB4-) DRG neurons, whereas large neurons and small neurons
that bound isolectin B4 (IB4+) were hardly affected. GBP (100 MUM) or PGB (10
MUM) were less effective than 20 MUM Mn(2+) in suppression of HVA ICa in small
DRG neurons. By contrast, 5-6 days of exposure to these alpha2delta-ligands was
more effective than 20 MUM Mn(2+) in reducing spontaneous excitatory postsynaptic
currents at synapses in substantia gelatinosa. Spinal actions of gabapentinoids
cannot therefore be ascribed to decreased expression of HVA Ca(2+) channels in
primary afferent nerve terminals. In substantia gelatinosa, 5-6 days of exposure
to PGB was more effective in inhibiting excitatory synaptic drive to putative
excitatory neurons than to putative inhibitory neurons. Although spontaneous
inhibitory postsynaptic currents were also attenuated, the overall long-term
effect of alpha2delta-ligands was to decrease network excitability as monitored
by confocal Ca(2+) imaging. We suggest that selective actions of alpha2delta
ligands on populations of DRG neurons may predict their selective attenuation of
excitatory transmission onto excitatory vs. inhibitory neurons in substantia
gelatinosa.
PMID- 25122704
TI - Increased intrinsic excitability of muscle vasoconstrictor preganglionic neurons
may contribute to the elevated sympathetic activity in hypertensive rats.
AB - Hypertension is associated with pathologically increased sympathetic drive to the
vasculature. This has been attributed to increased excitatory drive to
sympathetic preganglionic neurons (SPN) from brainstem cardiovascular control
centers. However, there is also evidence supporting increased intrinsic
excitability of SPN. To test this hypothesis, we made whole cell recordings of
muscle vasoconstrictor-like (MVClike) SPN in the working-heart brainstem
preparation of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto
(WKY) rats. The MVClike SPN have a higher spontaneous firing frequency in the SH
rat (3.85 +/- 0.4 vs. 2.44 +/- 0.4 Hz in WKY; P = 0.011) with greater respiratory
modulation of their activity. The action potentials of SH SPN had smaller,
shorter afterhyperpolarizations (AHPs) and showed diminished transient
rectification indicating suppression of an A-type potassium conductance (IA). We
developed mathematical models of the SPN to establish if changes in their
intrinsic properties in SH rats could account for their altered firing. Reduction
of the maximal conductance density of IA by 15-30% changed the excitability and
output of the model from the WKY to a SH profile, with increased firing
frequency, amplified respiratory modulation, and smaller AHPs. This change in
output is predominantly a consequence of altered synaptic integration. Consistent
with these in silico predictions, we found that intrathecal 4-aminopyridine (4
AP) increased sympathetic nerve activity, elevated perfusion pressure, and
augmented Traube-Hering waves. Our findings indicate that IA acts as a powerful
filter on incoming synaptic drive to SPN and that its diminution in the SH rat is
potentially sufficient to account for the increased sympathetic output underlying
hypertension.
PMID- 25122706
TI - Decoding stimulus duration from neural responses in the auditory midbrain.
AB - Neurons with responses selective for the duration of an auditory stimulus are
called duration-tuned neurons (DTNs). Temporal specificity in their spiking
suggests that one function of DTNs is to encode stimulus duration; however, the
efficacy of duration encoding by DTNs has yet to be investigated. Herein, we
characterize the information content of individual cells and a population of DTNs
from the mammalian inferior colliculus (IC) by measuring the stimulus-specific
information (SSI) and estimated Fisher information (FI) of spike count responses.
We found that SSI was typically greatest for those stimulus durations that evoked
maximum spike counts, defined as best duration (BD) stimuli, and that FI was
maximal for stimulus durations off BD where sensitivity to a change in duration
was greatest. Using population data, we demonstrate that a maximum likelihood
estimator (MLE) can accurately decode stimulus duration from evoked spike counts.
We also simulated a two-alternative forced choice task by having MLE models
decide whether two durations were the same or different. With this task we
measured the just-noticeable difference threshold for stimulus duration and
calculated the corresponding Weber fractions across the stimulus domain.
Altogether, these results demonstrate that the spiking responses of DTNs from the
mammalian IC contain sufficient information for the CNS to encode, decode, and
discriminate behaviorally relevant auditory signal durations.
PMID- 25122708
TI - Nerve growth factor alters the sensitivity of rat masseter muscle
mechanoreceptors to NMDA receptor activation.
AB - Intramuscular injection of nerve growth factor (NGF) into rat masseter muscle
induces a local mechanical sensitization that is greater in female than in male
rats. The duration of NGF-induced sensitization in male and female rats was
associated with an increase in peripheral N-methyl-d-aspartate (NMDA) receptor
expression by masseter muscle afferent fibers that began 3 days postinjection.
Here, we investigated the functional consequences of increased NMDA expression on
the response properties of masseter muscle mechanoreceptors. In vivo
extracellular single-unit electrophysiological recordings of trigeminal ganglion
neurons innervating the masseter muscle were performed in anesthetized rats 3
days after NGF injection (25 MUg/ml, 10 MUl) into the masseter muscle. Mechanical
activation threshold was assessed before and after intramuscular injection of
NMDA. NMDA injection induced mechanical sensitization in both sexes that was
increased significantly following NGF injection in the male rats but not in the
female rats. However, in female but not male rats, further examination found that
preadministration of NGF induced a greater sensitization in slow Adelta-fibers (2
7 m/s) than fast Adelta-fibers (7-12 m/s). This suggests that preadministration
of NGF had a different effect on slowly conducting mechanoreceptors in the female
rats compared with the male rats. Although previous studies have found an
association between estrogenic tone and NMDA activity, no correlation was
observed between NMDA-evoked mechanical sensitization and plasma estrogen level.
This study suggests NGF alters NMDA-induced mechanical sensitization in the
peripheral endings of masseter mechanoreceptors in a sexually dimorphic manner.
PMID- 25122709
TI - Visual selectivity for heading in the macaque ventral intraparietal area.
AB - The patterns of optic flow seen during self-motion can be used to determine the
direction of one's own heading. Tracking eye movements which typically occur
during everyday life alter this task since they add further retinal image motion
and (predictably) distort the retinal flow pattern. Humans employ both visual and
nonvisual (extraretinal) information to solve a heading task in such case.
Likewise, it has been shown that neurons in the monkey medial superior temporal
area (area MST) use both signals during the processing of self-motion
information. In this article we report that neurons in the macaque ventral
intraparietal area (area VIP) use visual information derived from the distorted
flow patterns to encode heading during (simulated) eye movements. We recorded
responses of VIP neurons to simple radial flow fields and to distorted flow
fields that simulated self-motion plus eye movements. In 59% of the cases, cell
responses compensated for the distortion and kept the same heading selectivity
irrespective of different simulated eye movements. In addition, response
modulations during real compared with simulated eye movements were smaller, being
consistent with reafferent signaling involved in the processing of the visual
consequences of eye movements in area VIP. We conclude that the motion
selectivities found in area VIP, like those in area MST, provide a way to
successfully analyze and use flow fields during self-motion and simultaneous
tracking movements.
PMID- 25122707
TI - Dopamine transporter gene susceptibility to methylation is associated with
impulsivity in nonhuman primates.
AB - Impulsivity, the predisposition to act without regard for negative consequences,
is a characteristic of several psychiatric disorders and is thought to result in
part from genetic variation in the untranslated region of the dopamine
transporter (DAT) gene. As the exact link between genetic mutations and
impulsivity has not been established, we used oculomotor behavior to characterize
rhesus monkeys as impulsive or calm and genetic/epigenetic analysis and positron
emission tomography (PET) to correlate phenotype to DAT genotype, DAT gene
methylation, and DAT availability. We found three single nucleotide polymorphisms
(SNPs) in the 3'-UTR of the DAT gene, one of which provided a potential site for
methylation in the impulsive group. Bisulfite analysis showed that the DNA of the
impulsive but not the calm subjects was methylated at one SNP. Because
genetic/epigenetic modifications could lead to differences in protein expression,
we measured DAT availability using [(18)F]2beta-carbomethoxy-3beta-(4
chlorophenyl)-8-(2-fluoroethyl)-nortropane ([(18)F]FECNT) PET and found higher
DAT availability in the internal globus pallidus, an output nucleus of the basal
ganglia, of the impulsive group. Higher DAT availability lowers dopamine levels,
potentially altering neuronal circuits involved in the initiation of action, thus
contributing to the impulsive phenotype. The association between increased
methylation in the DAT gene and greater DAT availability suggests that mutations
to the regulatory portion of the DAT gene lead to a susceptibility to epigenetic
modification resulting in a discrete behavioral phenotype.
PMID- 25122710
TI - Low-intensity electric fields induce two distinct response components in
neocortical neuronal populations.
AB - Low-intensity alternating electric fields applied to the scalp are capable of
modulating cortical activity and brain functions, but the underlying mechanisms
remain largely unknown. Here, we report two distinct components of voltage
sensitive dye signals induced by low-intensity, alternating electric fields in
rodent cortical slices: a "passive component," which corresponds to membrane
potential changes directly induced by the electric field; and an "active
component," which is a widespread depolarization that is dependent on excitatory
synaptic transmission. The passive component is stationary, with amplitude and
phase accurately reflecting the cortical cytoarchitecture. In contrast, the
active component is initiated from a local "hot spot" of activity and spreads to
a large population as a propagating wave with rich local dynamics. The
propagation of the active component may play a role in modulating large-scale
cortical activity by spreading a low level of excitation from a small initiation
point to a vast neuronal population.
PMID- 25122711
TI - Effects of millimeter wave irradiation and equivalent thermal heating on the
activity of individual neurons in the leech ganglion.
AB - Many of today's radiofrequency-emitting devices in telecommunication,
telemedicine, transportation safety, and security/military applications use the
millimeter wave (MMW) band (30-300 GHz). To evaluate the biological safety and
possible applications of this radiofrequency band for neuroscience and neurology,
we have investigated the physiological effects of low-intensity 60-GHz
electromagnetic irradiation on individual neurons in the leech midbody ganglia.
We applied incident power densities of 1, 2, and 4 mW/cm(2) to the whole ganglion
for a period of 1 min while recording the action potential with a standard sharp
electrode electrophysiology setup. For comparison, the recognized U.S. safe
exposure limit is 1 mW/cm(2) for 6 min. During the exposure to MMWs and gradual
bath heating at a rate of 0.04 degrees C/s (2.4 degrees C/min), the ganglionic
neurons exhibited similar dose-dependent hyperpolarization of the plasma membrane
and decrease in the action potential amplitude. However, narrowing of the action
potential half-width during MMW irradiation at 4 mW/cm(2) was 5 times more
pronounced compared with that during equivalent bath heating of 0.6 degrees C.
Even more dramatic difference in the effects of MMW irradiation and bath heating
was noted in the firing rate, which was suppressed at all applied MMW power
densities and increased in a dose-dependent manner during gradual bath heating.
The mechanism of enhanced narrowing of action potentials and suppressed firing by
MMW irradiation, compared with that by gradual bath heating, is hypothesized to
involve specific coupling of MMW energy with the neuronal plasma membrane.
PMID- 25122712
TI - The irregular firing properties of thalamic head direction cells mediate turn
specific modulation of the directional tuning curve.
AB - Head direction cells encode an animal's heading in the horizontal plane. However,
it is not clear why the directionality of a cell's mean firing rate differs for
clockwise, compared with counterclockwise, head turns (this difference is known
as the "separation angle") in anterior thalamus. Here we investigated in freely
behaving rats whether intrinsic neuronal firing properties are linked to this
phenomenon. We found a positive correlation between the separation angle and the
spiking variability of thalamic head direction cells. To test whether this link
is driven by hyperpolarization-inducing currents, we investigated the effect of
thalamic reticular inhibition during high-voltage spindles on directional
spiking. While the selective directional firing of thalamic neurons was
preserved, we found no evidence for entrainment of thalamic head direction cells
by high-voltage spindle oscillations. We then examined the role of depolarization
inducing currents in the formation of separation angle. Using a single
compartment Hodgkin-Huxley model, we show that modeled neurons fire with higher
frequencies during the ascending phase of sinusoidal current injection (mimicking
the head direction tuning curve) when simulated with higher high-threshold
calcium channel conductance. These findings demonstrate that the turn-specific
encoding of directional signal strongly depends on the ability of thalamic
neurons to fire irregularly in response to sinusoidal excitatory activation.
Another crucial factor for inducing phase lead to sinusoidal current injection
was the presence of spike-frequency adaptation current in the modeled neurons.
Our data support a model in which intrinsic biophysical properties of thalamic
neurons mediate the physiological encoding of directional information.
PMID- 25122715
TI - Locomotor training alters the behavior of flexor reflexes during walking in human
spinal cord injury.
AB - In humans, a chronic spinal cord injury (SCI) impairs the excitability of
pathways mediating early flexor reflexes and increases the excitability of late,
long-lasting flexor reflexes. We hypothesized that in individuals with SCI,
locomotor training will alter the behavior of these spinally mediated reflexes.
Nine individuals who had either chronic clinically motor complete or incomplete
SCI received an average of 44 locomotor training sessions. Flexor reflexes,
elicited via sural nerve stimulation of the right or left leg, were recorded from
the ipsilateral tibialis anterior (TA) muscle before and after body weight
support (BWS)-assisted treadmill training. The modulation pattern of the
ipsilateral TA responses following innocuous stimulation of the right foot was
also recorded in 10 healthy subjects while they stepped at 25% BWS to investigate
whether body unloading during walking affects the behavior of these responses.
Healthy subjects did not receive treadmill training. We observed a phase
dependent modulation of early TA flexor reflexes in healthy subjects with reduced
body weight during walking. The early TA flexor reflexes were increased at heel
contact, progressively decreased during the stance phase, and then increased
throughout the swing phase. In individuals with SCI, locomotor training induced
the reappearance of early TA flexor reflexes and changed the amplitude of late TA
flexor reflexes during walking. Both early and late TA flexor reflexes were
modulated in a phase-dependent pattern after training. These new findings support
the adaptive capability of the injured nervous system to return to a prelesion
excitability and integration state.
PMID- 25122714
TI - Minimum conditions for the induction of cortical spreading depression in brain
slices.
AB - Cortical spreading depression (CSD) occurs during various forms of brain injury
such as stroke, subarachnoid hemorrhage, and brain trauma, but it is also thought
to be the mechanism of the migraine aura. It is therefore expected to occur over
a range of conditions including the awake behaving state. Yet it is unclear how
such a massive depolarization could occur under relatively benign conditions.
Using a microfluidic device with focal stimulation capability in a mouse brain
slice model, we varied extracellular potassium concentration as well as the area
exposed to increased extracellular potassium to determine the minimum conditions
necessary to elicit CSD. Importantly, we focused on potassium levels that are
physiologically plausible (<=145 mM; the intracellular potassium concentration).
We found a strong correlation between the threshold concentration and the slice
area exposed to increased extracellular potassium: minimum area of exposure was
needed with the highest potassium concentration, while larger areas were needed
at lower concentrations. We also found that moderate elevations of extracellular
potassium were able to elicit CSD in relatively small estimated tissue volumes
that might be activated under noninjury conditions. Our results thus show that
CSD may be inducible under the conditions that expected in migraine aura as well
as those related to brain trauma.
PMID- 25122716
TI - Opposed optimal strategies of weighting somatosensory inputs for planning
reaching movements toward visual and proprioceptive targets.
AB - Behavioral studies have suggested that the brain uses a visual estimate of the
hand to plan reaching movements toward visual targets and somatosensory inputs in
the case of somatosensory targets. However, neural correlates for distinct coding
of the hand according to the sensory modality of the target have not yet been
identified. Here we tested the twofold hypothesis that the somatosensory input
from the reaching hand is facilitated and inhibited, respectively, when planning
movements toward somatosensory (unseen fingers) or visual targets. The weight of
the somatosensory inputs was assessed by measuring the amplitude of the
somatosensory evoked potential (SEP) resulting from vibration of the reaching
finger during movement planning. The target sensory modality had no significant
effect on SEP amplitude. However, Spearman's analyses showed significant
correlations between the SEPs and reaching errors. When planning movements toward
proprioceptive targets without visual feedback of the reaching hand, participants
showing the greater SEPs were those who produced the smaller directional errors.
Inversely, participants showing the smaller SEPs when planning movements toward
visual targets with visual feedback of the reaching hand were those who produced
the smaller directional errors. No significant correlation was found between the
SEPs and radial or amplitude errors. Our results indicate that the sensory
strategy for planning movements is highly flexible among individuals and also for
a given sensory context. Most importantly, they provide neural bases for the
suggestion that optimization of movement planning requires the target and the
reaching hand to both be represented in the same sensory modality.
PMID- 25122713
TI - Modulation of motoneuron firing by recurrent inhibition in the adult rat in vivo.
AB - Recent reports show that synaptic inhibition can modulate postsynaptic spike
timing without having strong effects on firing rate. Thus synaptic inhibition can
achieve multiplicity in neural circuit operation through variable modulation of
postsynaptic firing rate vs. timing. We tested this possibility for recurrent
inhibition (RI) of spinal motoneurons. In in vivo electrophysiological studies of
adult Wistar rats anesthetized by isoflurane, we examined repetitive firing of
individual lumbosacral motoneurons recorded in current clamp and modulated by
synchronous antidromic electrical stimulation of multiple motor axons and their
centrally projecting collateral branches. Antidromic stimulation produced
recurrent inhibitory postsynaptic potentials (RIPSPs) having properties similar
to those detailed in the cat. Although synchronous RI produced marked short-term
modulation of motoneuron spike timing and instantaneous firing rate, there was
little or no suppression of average firing rate. The bias in firing modulation of
timing over average rate was observed even for high-frequency RI stimulation (100
Hz), perhaps because of the brevity of RIPSPs, which were more than twofold
shorter during motoneuron firing compared with rest. These findings demonstrate
that RI in the mammalian spinal cord has the capacity to support and not impede
heightened motor pool activity, possibly during rapid, forceful movements.
PMID- 25122718
TI - Learning-related neuronal activity in the ventral lateral geniculate nucleus
during associative cerebellar learning.
AB - During delay eyeblink conditioning, rats learn to produce an eyelid-closure
conditioned response (CR) to a conditioned stimulus (CS), such as a light, which
precedes and coterminates with an unconditioned stimulus (US). Previous studies
have suggested that the ventral lateral geniculate nucleus (LGNv) might play an
important role in visual eyeblink conditioning by supplying visual sensory input
to the pontine nuclei (PN) and also receiving feedback from the cerebellum. No
prior study has investigated LGNv neuronal activity during eyeblink conditioning.
The present study used multiple tetrodes to monitor single-unit activity in the
rat LGNv during pre-exposure (CS only), unpaired CS/US, and paired CS-US training
conditions. This behavioral-training sequence was used to investigate
nonassociative- and associative-driven neuronal activity in the LGNv during
training. LGNv neuronal activity habituated during unpaired training and then
recovered from habituation during subsequent paired training, which may indicate
that the LGNv plays a role in attention to the CS. The amplitude of LGNv neuronal
activity correlated with CR production during paired but not unpaired CS/US
training. Cerebellar feedback to the LGNv may play a role in modulating LGNv
activity and attention to the CS during paired training. Based on the present
findings, we hypothesize that the role of LGNv in visual eyeblink conditioning
goes beyond simply routing visual CS information to the PN and involves
modulation of attention.
PMID- 25122720
TI - High-quality 3-dimensional imaging for patients with anomalous pulmonary veins.
AB - The branching pattern of pulmonary veins exhibits many variations. Here we
describe 2 patients with lung malignancies who were found to have pulmonary vein
anomalies. We performed video-assisted thoracoscopic lobectomies based on
preoperative simulations by 3-dimensional computed tomography. Using 3
dimensional computed tomography, a surgeon can easily construct digital images of
the patient's pulmonary vessels within a few minutes. Simulation using 3
dimensional computed tomography imaging is useful for further understanding of
the surgical anatomy.
PMID- 25122719
TI - Gender Differences in Health Literacy Among Korean Adults: Do Women Have a Higher
Level of Health Literacy Than Men?
AB - The role of gender in determining the level of health literacy in Korean adults
is unclear. This study aimed to investigate the level of health literacy in
Korean adults and identify factors associated with health literacy by gender.
This study employed a cross-sectional survey design with a convenient sample of
585 community-dwelling Korean adults age19 years and older. Health literacy was
measured by using eight items selected from Chew et al.'s 16-question self
reported health literacy measure. In accordance with Andersen's health behavior
model, predisposing, enabling, and need factors were included in the multiple
regression model. Women indicated a higher level of health literacy than men in
understanding medical forms, directions on medication bottles, and written
information offered by health care providers. Additionally, for Korean women, a
higher level of health literacy was associated with attaining a higher education
level and having a consistent place to receive care. Unmarried men and men who
had higher self-rated health reported a higher level of health literacy compared
with their counterparts. Lower level of depression and higher monthly income were
significantly linked to a higher level of health literacy in both men and women.
This study has established the importance of gender differences in health
literacy and suggests gender-specific intervention may be warranted to reduce the
existing gap in health literacy in both Korean men and women. Future research
should replicate this study to confirm whether or not our finding is an
international phenomenon.
PMID- 25122721
TI - Genetic polymorphisms in preoperative myocardial infarction.
AB - OBJECTIVE: This study compared plasminogen activator inhibitor 1 and
methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in patients
with myocardial infarction with ST-segment elevation before undergoing to
coronary artery bypass grafting, and in patients who had previously undergone
coronary artery bypass grafting. METHOD: Seventy patients with myocardial
infarction with ST-segment elevation, scheduled to undergo coronary artery bypass
grafting, were included in the study group, and 70 patients who had previously
undergone coronary artery bypass grafting were included in the control group.
Genetic polymorphisms were determined using real-time polymerase chain reaction
methods. RESULTS: Our data showed that there were no significant differences in
plasminogen activator inhibitor 1 and methylenetetrahydrofolate reductase C677T
and A1298C polymorphisms or allele frequencies between the 2 groups. CONCLUSION:
Plasminogen activator inhibitor 1 and methylenetetrahydrofolate reductase C677T
and A1298C polymorphisms were not associated risk factors in patients who had
myocardial infarction with ST-segment elevation and planned to have coronary
artery bypass grafting.
PMID- 25122717
TI - Elevated serotonergic signaling amplifies synaptic noise and facilitates the
emergence of epileptiform network oscillations.
AB - Serotonin fibers densely innervate the cortical sheath to regulate neuronal
excitability, but its role in shaping network dynamics remains undetermined. We
show that serotonin provides an excitatory tone to cortical neurons in the form
of spontaneous synaptic noise through 5-HT3 receptors, which is persistent and
can be augmented using fluoxetine, a selective serotonin re-uptake inhibitor.
Augmented serotonin signaling also increases cortical network activity by
enhancing synaptic excitation through activation of 5-HT2 receptors. This in turn
facilitates the emergence of epileptiform network oscillations (10-16 Hz) known
as fast runs. A computational model of cortical dynamics demonstrates that these
two combined mechanisms, increased background synaptic noise and enhanced
synaptic excitation, are sufficient to replicate the emergence fast runs and
their statistics. Consistent with these findings, we show that blocking 5-HT2
receptors in vivo significantly raises the threshold for convulsant-induced
seizures.
PMID- 25122722
TI - A case of right superior vena cava draining into the left atrial roof.
AB - We report the multidisciplinary consideration in a case of right superior vena
cava draining into the left atrial roof. A 12-year-old boy was diagnosed with a
sinus venosus-type atrial septal defect associated with anomalous right upper
pulmonary venous return. However, intraoperative inspection showed the right
superior vena cava draining into the left atrial roof, associated with anomalous
right upper pulmonary venous return. An anatomical radical operation was
performed using a modified conventional technique.
PMID- 25122723
TI - Single coronary artery anomaly without previous myocardial infarction does not
cause ischemic mitral insufficiency.
PMID- 25122724
TI - Opioid therapy for knee osteoarthritis and postoperative persistent pain after
knee arthroplasty.
PMID- 25122725
TI - Mortality in patients with giant cell arteritis.
AB - OBJECTIVE: The aim of this study was to examine whether GCA is associated with
increased mortality. METHODS: We conducted a nationwide population-based cohort
study including all individuals who between 1993 and 2011 were registered in the
Danish National Hospital Register and the Danish Pathology Register with a biopsy
proven diagnosis of GCA (n = 1787). Through the Danish Civil Registration System
we identified a comparison cohort of 33 953 persons from the background
population, individually matched on age and sex. Data on causes of death were
obtained from the Danish Registry of Causes of Death. We used Poisson regression
to determine mortality rate ratios as estimates of relative risk of death and
specific causes of death. RESULTS: Compared with the general population, the
relative risk (RR) of death in patients diagnosed with GCA was 1.17 (95% CI 1.01,
1.36) and 1.22 (95% CI 1.05, 1.41) 0-2 years and >10 years after diagnosis,
respectively, whereas we observed no increased mortality during the follow-up
period of 2-10 years [RR 0.96 (95% CI 0.88, 1.05)]. The increased mortality
during the first 2 years of follow-up was mainly due to diseases of the
circulatory system, including aortic aneurisms. CONCLUSION: GCA is associated
with slightly increased early and late mortality.
PMID- 25122726
TI - The global anti-phospholipid syndrome score in primary APS.
AB - OBJECTIVE: The aim of this study was to evaluate the clinical relevance of the
global APS score (GAPSS) in a cohort of primary APS patients. METHODS: This study
included 62 consecutive patients with primary APS. Data on clinical
manifestations, conventional cardiovascular risk factors and aPL profile were
collected. The GAPSS was calculated for each patient by adding together the
points corresponding to the risk factors, based on a linear transformation
derived from the beta regression coefficient as follows: 3 for hyperlipidaemia, 1
for arterial hypertension, 5 for aCL IgG/IgM, 4 for anti-beta2 glycoprotein I
IgG/IgM, 3 for aPS-PT IgG/IgM and 4 for LA. RESULTS: Higher GAPSS values were
seen in patients who experienced thrombosis alone when compared with those with
pregnancy loss alone [11.5 (S.D. 4.6) and 8.7 (S.D. 3.2), P = 0.04]. Patients
with both thrombosis and pregnancy loss showed higher GAPSS than those with
pregnancy loss alone [12.5 (S.D. 4.6) vs 8.7 (S.D. 3.2), P = 0.02]. Higher GAPSS
values were also shown after subgrouping for the site of thrombosis when compared
with pregnancy loss alone [12.2 (S.D. 5.2) for arterial thrombosis, 12.0 (S.D.
4.0) for venous vs 8.7 (S.D. 3.2), P = 0.02 and P = 0.04, respectively]. Patients
with thrombotic recurrences showed higher GAPSS values when compared with those
without recurrence [13.7 (S.D. 3.1) vs 9.4 (S.D. 3.9), P = 0.02]. This was also
seen when comparing recurrences vs no recurrences independently of the site of
the thrombotic event [13.9 (S.D. 3.6) vs 11.0 (S.D. 4.3), P = 0.01 for arterial
and 13.6 (S.D. 2.18) vs 8.91 (S.D. 3.6), P < 0.01 for venous thrombosis]. GAPSS
values >=11 were strongly associated with a higher risk of recurrence [odds ratio
(OR) 18.27 (95% CI 3.74, 114.5) for a cut-off of 11, OR 20.64 (95% CI 3.92,
185.92) for a cut-off of 12 and 21.64 (95% CI 3.89, 189.56) for a cut-off of 15].
GAPSS values >=11 seemed to have the best risk accuracy in terms of sensitivity
and specificity. CONCLUSION: The GAPSS is demonstrated to be a valid tool for a
substantial improvement in risk stratification for thrombosis in primary APS.
PMID- 25122728
TI - Tall cell variant of papillary thyroid carcinoma in children: report of three
cases with long-term follow-up from a single institution.
AB - Papillary thyroid carcinoma (PTC), tall cell (TC) variant, is exceptional in
children. In adults it represents about 20% of PTCs, featuring a high-risk
neoplasm, with a 4-fold risk of relapse and a 20-fold relapse-related risk of
death. Out of 42 cases of pediatric PTCs, we found 3 cases of PTC-TC (7%) with
clinical data at onset and follow-up up to June 2014. They were 3 females aged
13, 15, and 15 years. Local extrathyroid extension was present in 2 cases.
Neither nodal nor distant metastases were found. Two patients underwent
hemithyroidectomy and 1 patient a total thyroidectomy, followed in all cases by
life-long suppressive hormonal therapy. On follow-up, the patients were alive and
well after 29, 24, and 29 years, respectively. The rarity of PTC-TC in children
was confirmed. The behavior was indolent after a median follow-up of about 29
years, following treatment with hemithyroidectomy in 2 cases and controlled by
suppressive hormonal therapy. The results of this series, albeit small, suggest
that TC morphology in PTC does not carry the same negative prognostic
significance in children as it does in adults. A conservative approach should
therefore be considered for these 'pediatric type' cases of this tumor type.
PMID- 25122730
TI - Modigliani-like art in surgical pathology.
PMID- 25122727
TI - Predictive impact on medium-term mortality of hematological parameters in Acute
Coronary Syndromes: added value on top of GRACE risk score.
AB - BACKGROUND: Red Cell Distribution Width (RDW) prognostic value in patients with
Acute Coronary Syndrome (ACS) has been well validated whereas that of Platelet
Distribution Width (PDW) is less well known. OBJECTIVES: Investigate the
incremental prognostic value, on top of GRACE risk score, of a new variable
resulting from the combination of RDW and PDW. METHODS: Consecutive patients with
ACS. Complete blood count, with RDW and PDW, was obtained. Primary endpoint was
one-year all-cause mortality and Cox regression models were used to measure the
influence of RDW and PDW on patients' survival time. A new combination
categorical variable (RDW/PDW) was created with both discretized RDW and PDW and
logistic regression models were used. Predictive value and discriminative ability
of the model with GRACE risk score alone and of the model with inclusion of
RDW/PDW was assessed. RESULTS: We included 787 patients. Hospital and one-year
mortality rates were 5.1% and 7.8%, respectively. Both continuous RDW and PDW
were independent predictors of death. The best cut-off for RDW was 13.9%, and
14.5% for PDW. Inclusion of RDW/PDW in a model with GRACE risk score improved the
AUC from 0.81 (95% CI 0.75-0.86) to 0.84 (95% CI 0.79-0.90) (p=0.024) with an
improvement in total NRI (56%) and IDI (0.048). CONCLUSIONS: Simple markers such
as RDW and PDW can be useful in risk stratification of death after ACS. Combining
both markers with GRACE risk score improved the predictive value for all-cause
mortality and reduced the estimated risk of those who did not die.
PMID- 25122729
TI - Art and human expression in histology.
PMID- 25122731
TI - Measuring progress in global health.
PMID- 25122732
TI - Cognitive Testing to Identify Children With ADHD Who Do and Do Not Respond to
Methylphenidate.
AB - OBJECTIVE: To explore the utility of cognitive measures for predicting response
of children and adolescents to methylphenidate (MPH). METHOD: Participants from
the International Study to Predict Optimized Treatment-in ADHD (iSPOT-A)
completed a cognitive test battery prior to receiving 6 weeks of MPH. The
responder criterion was a 25% reduction in ADHD-Rating Scale-IV scores. Receiver
Operator Characteristics (ROC) classified non-responders from responders with
maximal sensitivity and specificity. RESULTS: Overall, 62% of participants
responded to MPH. Response rates for ROC-identified groups ranged from 18% to
85%. Non-responders showed compromised cognition related to switching of
attention, sustained attention, planning, and impulsivity. One group of
responders were 10 years of age or older and had impaired switching of attention
and impulsivity; a second group had enhanced switching of attention, normal or
higher Continuous Performance Task (CPT) scores, and above average scores on
digit span. CONCLUSION: Cognitive tests may provide a simple, low-cost tool for
treatment planning for children and adolescents with ADHD.
PMID- 25122733
TI - Researchers push back against overhauling clinical trials.
PMID- 25122734
TI - Water pipe smoking: not risk free.
PMID- 25122737
TI - Hormone therapy can wait in PSA-only relapse.
PMID- 25122735
TI - Identifying cancer mutations as therapeutic targets.
PMID- 25122739
TI - The enemy of my enemy is my friend: intraguild predation between invaders and
natives facilitates coexistence with shared invasive prey.
AB - Understanding and predicting the outcomes of biological invasions is challenging
where multiple invader and native species interact. We hypothesize that
antagonistic interactions between invaders and natives could divert their impact
on subsequent invasive species, thus facilitating coexistence. From field data,
we found that, when existing together in freshwater sites, the native amphipod
Gammarus duebeni celticus and a previous invader G. pulex appear to facilitate
the establishment of a second invader, their shared prey Crangonyx
pseudogracilis. Indeed, the latter species was rarely found at sites where each
Gammarus species was present on its own. Experiments indicated that this may be
the result of G. d. celticus and G. pulex engaging in more intraguild predation
(IGP) than cannibalism; when the 'enemy' of either Gammarus species was present,
that is, the other Gammarus species, C. pseudogracilis significantly more often
escaped predation. Thus, the presence of mutual enemies and the stronger inter-
than intraspecific interactions they engage in can facilitate other invaders.
With some invasive species such as C. pseudogracilis having no known detrimental
effects on native species, and indeed having some positive ecological effects, we
also conclude that some invasions could promote biodiversity and ecosystem
functioning.
PMID- 25122740
TI - Preterm birth is associated with an increased fundamental frequency of
spontaneous crying in human infants at term-equivalent age.
AB - Human infant crying has been researched as a non-invasive tool for assessing
neurophysiological states at an early developmental stage. Little is known about
the acoustic features of spontaneous cries in preterm infants, although their
pain-induced cries are at a higher fundamental frequency (F0) before term
equivalent age. In this study, we investigated the effects of gestational age,
body size at recording and intrauterine growth retardation (IUGR) on the F0 of
spontaneous cries in healthy preterm and full-term infants at term-equivalent
age. We found that shorter gestational age was significantly associated with
higher F0, although neither smaller body size at recording nor IUGR was related
to increased F0 in preterm infants. These findings suggest that the increased F0
of spontaneous cries is not caused by their smaller body size, but instead might
be caused by more complicated neurophysiological states owing to their different
intrauterine and extrauterine experiences.
PMID- 25122741
TI - Size matters: plasticity in metabolic scaling shows body-size may modulate
responses to climate change.
AB - Variability in metabolic scaling in animals, the relationship between metabolic
rate ( R: ) and body mass ( M: ), has been a source of debate and controversy for
decades. R: is proportional to MB: , the precise value of B: much debated, but
historically considered equal in all organisms. Recent metabolic theory, however,
predicts B: to vary among species with ecology and metabolic level, and may also
vary within species under different abiotic conditions. Under climate change,
most species will experience increased temperatures, and marine organisms will
experience the additional stressor of decreased seawater pH ('ocean
acidification'). Responses to these environmental changes are modulated by myriad
species-specific factors. Body-size is a fundamental biological parameter, but
its modulating role is relatively unexplored. Here, we show that changes to
metabolic scaling reveal asymmetric responses to stressors across body-size
ranges; B: is systematically decreased under increasing temperature in three
grazing molluscs, indicating smaller individuals were more responsive to warming.
Larger individuals were, however, more responsive to reduced seawater pH in low
temperatures. These alterations to the allometry of metabolism highlight abiotic
control of metabolic scaling, and indicate that responses to climate warming and
ocean acidification may be modulated by body-size.
PMID- 25122742
TI - Efficient nearest neighbors via robust sparse hashing.
AB - This paper presents a new nearest neighbor (NN) retrieval framework: robust
sparse hashing (RSH). Our approach is inspired by the success of dictionary
learning for sparse coding. Our key idea is to sparse code the data using a
learned dictionary, and then to generate hash codes out of these sparse codes for
accurate and fast NN retrieval. But, direct application of sparse coding to NN
retrieval poses a technical difficulty: when data are noisy or uncertain (which
is the case with most real-world data sets), for a query point, an exact match of
the hash code generated from the sparse code seldom happens, thereby breaking the
NN retrieval. Borrowing ideas from robust optimization theory, we circumvent this
difficulty via our novel robust dictionary learning and sparse coding framework
called RSH, by learning dictionaries on the robustified counterparts of the
perturbed data points. The algorithm is applied to NN retrieval on both simulated
and real-world data. Our results demonstrate that RSH holds significant promise
for efficient NN retrieval against the state of the art.
PMID- 25122743
TI - Monte Carlo non-local means: random sampling for large-scale image filtering.
AB - We propose a randomized version of the nonlocal means (NLM) algorithm for large
scale image filtering. The new algorithm, called Monte Carlo nonlocal means
(MCNLM), speeds up the classical NLM by computing a small subset of image patch
distances, which are randomly selected according to a designed sampling pattern.
We make two contributions. First, we analyze the performance of the MCNLM
algorithm and show that, for large images or large external image databases, the
random outcomes of MCNLM are tightly concentrated around the deterministic full
NLM result. In particular, our error probability bounds show that, at any given
sampling ratio, the probability for MCNLM to have a large deviation from the
original NLM solution decays exponentially as the size of the image or database
grows. Second, we derive explicit formulas for optimal sampling patterns that
minimize the error probability bound by exploiting partial knowledge of the
pairwise similarity weights. Numerical experiments show that MCNLM is competitive
with other state-of-the-art fast NLM algorithms for single-image denoising. When
applied to denoising images using an external database containing ten billion
patches, MCNLM returns a randomized solution that is within 0.2 dB of the full
NLM solution while reducing the runtime by three orders of magnitude.
PMID- 25122744
TI - Mycobacterium RbpA cooperates with the stress-response sigmaB subunit of RNA
polymerase in promoter DNA unwinding.
AB - RbpA, a transcriptional activator that is essential for Mycobacterium
tuberculosis replication and survival during antibiotic treatment, binds to RNA
polymerase (RNAP) in the absence of promoter DNA. It has been hypothesized that
RbpA stimulates housekeeping gene expression by promoting assembly of the
sigma(A) subunit with core RNAP. Here, using a purified in vitro transcription
system of M. tuberculosis, we show that RbpA functions in a promoter-dependent
manner as a companion of RNAP essential for promoter DNA unwinding and formation
of the catalytically active open promoter complex (RPo). Screening for RbpA
activity using a full panel of the M. tuberculosis sigma subunits demonstrated
that RbpA targets sigma(A) and stress-response sigma(B), but not the alternative
sigma subunits from the groups 3 and 4. In contrast to sigma(A), the sigma(B)
subunit activity displayed stringent dependency upon RbpA. These results suggest
that RbpA-dependent control of RPo formation provides a mechanism for tuning gene
expression during the switch between different physiological states, and in the
stress response.
PMID- 25122745
TI - Analysis of an artificial zinc finger epigenetic modulator: widespread binding
but limited regulation.
AB - Artificial transcription factors (ATFs) and genomic nucleases based on a DNA
binding platform consisting of multiple zinc finger domains are currently being
developed for clinical applications. However, no genome-wide investigations into
their binding specificity have been performed. We have created six-finger ATFs to
target two different 18 nt regions of the human SOX2 promoter; each ATF is
constructed such that it contains or lacks a super KRAB domain (SKD) that
interacts with a complex containing repressive histone methyltransferases. ChIP
seq analysis of the effector-free ATFs in MCF7 breast cancer cells identified
thousands of binding sites, mostly in promoter regions; the addition of an SKD
domain increased the number of binding sites ~ 5-fold, with a majority of the new
sites located outside of promoters. De novo motif analyses suggest that the lack
of binding specificity is due to subsets of the finger domains being used for
genomic interactions. Although the ATFs display widespread binding, few genes
showed expression differences; genes repressed by the ATF-SKD have stronger
binding sites and are more enriched for a 12 nt motif. Interestingly, epigenetic
analyses indicate that the transcriptional repression caused by the ATF-SKD is
not due to changes in active histone modifications.
PMID- 25122747
TI - Systematic exploration of a class of hydrophobic unnatural base pairs yields
multiple new candidates for the expansion of the genetic alphabet.
AB - We have developed a family of unnatural base pairs (UBPs), which rely on
hydrophobic and packing interactions for pairing and which are well replicated
and transcribed. While the pair formed between d5SICS and dNaM (d5SICS-dNaM) has
received the most attention, and has been used to expand the genetic alphabet of
a living organism, recent efforts have identified dTPT3-dNaM, which is replicated
with even higher fidelity. These efforts also resulted in more UBPs than could be
independently analyzed, and thus we now report a PCR-based screen to identify the
most promising. While we found that dTPT3-dNaM is generally the most promising
UBP, we identified several others that are replicated nearly as well and
significantly better than d5SICS-dNaM, and are thus viable candidates for the
expansion of the genetic alphabet of a living organism. Moreover, the results
suggest that continued optimization should be possible, and that the putatively
essential hydrogen-bond acceptor at the position ortho to the glycosidic linkage
may not be required. These results clearly demonstrate the generality of
hydrophobic forces for the control of base pairing within DNA, provide a wealth
of new structure-activity relationship data and importantly identify multiple new
candidates for in vivo evaluation and further optimization.
PMID- 25122746
TI - Multiplex CRISPR/Cas9-based genome engineering from a single lentiviral vector.
AB - Engineered DNA-binding proteins that manipulate the human genome and
transcriptome have enabled rapid advances in biomedical research. In particular,
the RNA-guided CRISPR/Cas9 system has recently been engineered to create site
specific double-strand breaks for genome editing or to direct targeted
transcriptional regulation. A unique capability of the CRISPR/Cas9 system is
multiplex genome engineering by delivering a single Cas9 enzyme and two or more
single guide RNAs (sgRNAs) targeted to distinct genomic sites. This approach can
be used to simultaneously create multiple DNA breaks or to target multiple
transcriptional activators to a single promoter for synergistic enhancement of
gene induction. To address the need for uniform and sustained delivery of
multiplex CRISPR/Cas9-based genome engineering tools, we developed a single
lentiviral system to express a Cas9 variant, a reporter gene and up to four
sgRNAs from independent RNA polymerase III promoters that are incorporated into
the vector by a convenient Golden Gate cloning method. Each sgRNA is efficiently
expressed and can mediate multiplex gene editing and sustained transcriptional
activation in immortalized and primary human cells. This delivery system will be
significant to enabling the potential of CRISPR/Cas9-based multiplex genome
engineering in diverse cell types.
PMID- 25122748
TI - Probing the elastic limit of DNA bending.
AB - Sharp bending of double-stranded DNA (dsDNA) plays an essential role in genome
structure and function. However, the elastic limit of dsDNA bending remains
controversial. Here, we measured the opening rates of small dsDNA loops with
contour lengths ranging between 40 and 200 bp using single-molecule Fluorescence
Resonance Energy Transfer. The relationship of loop lifetime to loop size
revealed a critical transition in bending stress. Above the critical loop size,
the loop lifetime changed with loop size in a manner consistent with elastic
bending stress, but below it, became less sensitive to loop size, indicative of
softened dsDNA. The critical loop size increased from ~ 60 bp to ~ 100 bp with
the addition of 5 mM magnesium. We show that our result is in quantitative
agreement with the kinkable worm-like chain model, and furthermore, can reproduce
previously reported looping probabilities of dsDNA over the range between 50 and
200 bp. Our findings shed new light on the energetics of sharply bent dsDNA.
PMID- 25122749
TI - Molecular insights into replication initiation by Qbeta replicase using ribosomal
protein S1.
AB - Ribosomal protein S1, consisting of six contiguous OB-folds, is the largest
ribosomal protein and is essential for translation initiation in Escherichia
coli. S1 is also one of the three essential host-derived subunits of Qbeta
replicase, together with EF-Tu and EF-Ts, for Qbeta RNA replication in E. coli.
We analyzed the crystal structure of Qbeta replicase, consisting of the virus
encoded RNA-dependent RNA polymerase (beta-subunit), EF-Tu, EF-Ts and the N
terminal half of S1, which is capable of initiating Qbeta RNA replication.
Structural and biochemical studies revealed that the two N-terminal OB-folds of
S1 anchor S1 onto the beta-subunit, and the third OB-fold is mobile and protrudes
beyond the surface of the beta-subunit. The third OB-fold mainly interacts with a
specific RNA fragment derived from the internal region of Qbeta RNA, and its RNA
binding ability is required for replication initiation of Qbeta RNA. Thus, the
third mobile OB-fold of S1, which is spatially anchored near the surface of the
beta-subunit, primarily recruits the Qbeta RNA toward the beta-subunit, leading
to the specific and efficient replication initiation of Qbeta RNA, and S1
functions as a replication initiation factor, beyond its established function in
protein synthesis.
PMID- 25122751
TI - Binding of the transcription factor Atf1 to promoters serves as a barrier to
phase nucleosome arrays and avoid cryptic transcription.
AB - Schizosaccharomyces pombe displays a large transcriptional response common to
several stress conditions, regulated primarily by the transcription factor Atf1.
Atf1-dependent promoters contain especially broad nucleosome depleted regions
(NDRs) prior to stress imposition. We show here that basal binding of Atf1 to
these promoters competes with histones to create wider NDRs at stress genes.
Moreover, deletion of atf1 results in nucleosome disorganization specifically at
stress coding regions and derepresses antisense transcription. Our data indicate
that the transcription factor binding to promoters acts as an effective barrier
to fix the +1 nucleosome and phase downstream nucleosome arrays to prevent
cryptic transcription.
PMID- 25122750
TI - Negative regulation of the interferon response by an interferon-induced long non
coding RNA.
AB - Long non-coding RNAs (lncRNAs) play critical roles in diverse cellular processes;
however, their involvement in many critical aspects of the immune response
including the interferon (IFN) response remains poorly understood. To address
this gap, we compared the global gene expression pattern of primary human
hepatocytes before and at three time points after treatment with IFN-alpha. Among
~ 200 IFN-induced lncRNAs, one transcript showed ~ 100-fold induction. This RNA,
which we named lncRNA-CMPK2, was a spliced, polyadenylated nuclear transcript
that was induced by IFN in diverse cell types from human and mouse. Similar to
protein-coding IFN-stimulated genes (ISGs), its induction was dependent on JAK
STAT signaling. Intriguingly, knockdown of lncRNA-CMPK2 resulted in a marked
reduction in HCV replication in IFN-stimulated hepatocytes, suggesting that it
could affect the antiviral role of IFN. We could show that lncRNA-CMPK2 knockdown
resulted in upregulation of several protein-coding antiviral ISGs. The observed
upregulation was caused by an increase in both basal and IFN-stimulated
transcription, consistent with loss of transcriptional inhibition in knockdown
cells. These results indicate that the IFN response involves a lncRNA-mediated
negative regulatory mechanism. lncRNA-CMPK2 was strongly upregulated in a subset
of HCV-infected human livers, suggesting a role in modulation of the IFN response
in vivo.
PMID- 25122752
TI - The 9-1-1 checkpoint clamp stimulates DNA resection by Dna2-Sgs1 and Exo1.
AB - Single-stranded DNA (ssDNA) at DNA ends is an important regulator of the DNA
damage response. Resection, the generation of ssDNA, affects DNA damage
checkpoint activation, DNA repair pathway choice, ssDNA-associated mutation and
replication fork stability. In eukaryotes, extensive DNA resection requires the
nuclease Exo1 and nuclease/helicase pair: Dna2 and Sgs1(BLM). How Exo1 and Dna2
Sgs1(BLM) coordinate during resection remains poorly understood. The DNA damage
checkpoint clamp (the 9-1-1 complex) has been reported to play an important role
in stimulating resection but the exact mechanism remains unclear. Here we show
that the human 9-1-1 complex enhances the cleavage of DNA by both DNA2 and EXO1
in vitro, showing that the resection-stimulatory role of the 9-1-1 complex is
direct. We also show that in Saccharomyces cerevisiae, the 9-1-1 complex promotes
both Dna2-Sgs1 and Exo1-dependent resection in response to uncapped telomeres.
Our results suggest that the 9-1-1 complex facilitates resection by recruiting
both Dna2-Sgs1 and Exo1 to sites of resection. This activity of the 9-1-1 complex
in supporting resection is strongly inhibited by the checkpoint adaptor
Rad9(53BP1). Our results provide important mechanistic insights into how DNA
resection is regulated by checkpoint proteins and have implications for genome
stability in eukaryotes.
PMID- 25122753
TI - An intensity ratio of interlocking loops determines circadian period length.
AB - Circadian clocks allow organisms to orchestrate the daily rhythms in physiology
and behaviors, and disruption of circadian rhythmicity can profoundly affect
fitness. The mammalian circadian oscillator consists of a negative primary
feedback loop and is associated with some 'auxiliary' loops. This raises the
questions of how these interlocking loops coordinate to regulate the period and
maintain its robustness. Here, we focused on the REV-ERBalpha/Cry1 auxiliary
loop, consisting of Rev-Erbalpha/ROR-binding elements (RORE) mediated Cry1
transcription, coordinates with the negative primary feedback loop to modulate
the mammalian circadian period. The silicon simulation revealed an unexpected
rule: the intensity ratio of the primary loop to the auxiliary loop is inversely
related to the period length, even when post-translational feedback is fixed.
Then we measured the mRNA levels from two loops in 10-mutant mice and observed
the similar monotonic relationship. Additionally, our simulation and the
experimental results in human osteosarcoma cells suggest that a coupling effect
between the numerator and denominator of this intensity ratio ensures the
robustness of circadian period and, therefore, provides an efficient means of
correcting circadian disorders. This ratio rule highlights the contribution of
the transcriptional architecture to the period dynamics and might be helpful in
the construction of synthetic oscillators.
PMID- 25122754
TI - DNA2 cooperates with the WRN and BLM RecQ helicases to mediate long-range DNA end
resection in human cells.
AB - The 5'-3' resection of DNA ends is a prerequisite for the repair of DNA double
strand breaks by homologous recombination, microhomology-mediated end joining,
and single strand annealing. Recent studies in yeast have shown that, following
initial DNA end processing by the Mre11-Rad50-Xrs2 complex and Sae2, the
extension of resection tracts is mediated either by exonuclease 1 or by combined
activities of the RecQ family DNA helicase Sgs1 and the helicase/endonuclease
Dna2. Although human DNA2 has been shown to cooperate with the BLM helicase to
catalyze the resection of DNA ends, it remains a matter of debate whether another
human RecQ helicase, WRN, can substitute for BLM in DNA2-catalyzed resection.
Here we present evidence that WRN and BLM act epistatically with DNA2 to promote
the long-range resection of double strand break ends in human cells. Our
biochemical experiments show that WRN and DNA2 interact physically and coordinate
their enzymatic activities to mediate 5'-3' DNA end resection in a reaction
dependent on RPA. In addition, we present in vitro and in vivo data suggesting
that BLM promotes DNA end resection as part of the BLM-TOPOIIIalpha-RMI1-RMI2
complex. Our study provides new mechanistic insights into the process of DNA end
resection in mammalian cells.
PMID- 25122755
TI - Kinesin-2 KIF3AB exhibits novel ATPase characteristics.
AB - KIF3AB is an N-terminal processive kinesin-2 family member best known for its
role in intraflagellar transport. There has been significant interest in KIF3AB
in defining the key principles that underlie the processivity of KIF3AB in
comparison with homodimeric processive kinesins. To define the ATPase mechanism
and coordination of KIF3A and KIF3B stepping, a presteady-state kinetic analysis
was pursued. For these studies, a truncated murine KIF3AB was generated. The
results presented show that microtubule association was fast at 5.7 MUm(-1) s(
1), followed by rate-limiting ADP release at 12.8 s(-1). ATP binding at 7.5 MUm(
1) s(-1) was followed by an ATP-promoted isomerization at 84 s(-1) to form the
intermediate poised for ATP hydrolysis, which then occurred at 33 s(-1). ATP
hydrolysis was required for dissociation of the microtubule.KIF3AB complex, which
was observed at 22 s(-1). The dissociation step showed an apparent affinity for
ATP that was very weak (K1/2,ATP at 133 MUm). Moreover, the linear fit of the
initial ATP concentration dependence of the dissociation kinetics revealed an
apparent second-order rate constant at 0.09 MUm(-1) s(-1), which is inconsistent
with fast ATP binding at 7.5 MUm(-1) s(-1) and a Kd ,ATP at 6.1 MUm. These
results suggest that ATP binding per se cannot account for the apparent weak
K1/2,ATP at 133 MUm. The steady-state ATPase Km ,ATP, as well as the dissociation
kinetics, reveal an unusual property of KIF3AB that is not yet well understood
and also suggests that the mechanochemistry of KIF3AB is tuned somewhat
differently from homodimeric processive kinesins.
PMID- 25122756
TI - A novel eliminase from a marine bacterium that degrades hyaluronan and
chondroitin sulfate.
AB - Lyases cleave glycosaminoglycans (GAGs) in an eliminative mechanism and are
important tools for the structural analysis and oligosaccharide preparation of
GAGs. Various GAG lyases have been identified from terrestrial but not marine
organisms even though marine animals are rich in GAGs with unique structures and
functions. Herein we isolated a novel GAG lyase for the first time from the
marine bacterium Vibrio sp. FC509 and then recombinantly expressed and
characterized it. It showed strong lyase activity toward hyaluronan (HA) and
chondroitin sulfate (CS) and was designated as HA and CS lyase (HCLase). It
exhibited the highest activities to both substrates at pH 8.0 and 0.5 m NaCl at
30 degrees C. Its activity toward HA was less sensitive to pH than its CS lyase
activity. As with most other marine enzymes, HCLase is a halophilic enzyme and
very stable at temperatures from 0 to 40 degrees C for up to 24 h, but its
activity is independent of divalent metal ions. The specific activity of HCLase
against HA and CS reached a markedly high level of hundreds of thousands units/mg
of protein under optimum conditions. The HCLase-resistant tetrasaccharide
Delta(4,5)HexUAalpha1-3GalNAc(6-O-sulfate)beta1-4GlcUA(2-O-sulfate)beta1
3GalNAc(6-O-sulfate) was isolated from CS-D, the structure of which indicated
that HCLase could not cleave the galactosaminidic linkage bound to 2-O-sulfated d
glucuronic acid (GlcUA) in CS chains. Site-directed mutagenesis indicated that
HCLase may work via a catalytic mechanism in which Tyr-His acts as the Bronsted
base and acid. Thus, the identification of HCLase provides a useful tool for HA-
and CS-related research and applications.
PMID- 25122757
TI - The atomic resolution structure of human AlkB homolog 7 (ALKBH7), a key protein
for programmed necrosis and fat metabolism.
AB - ALKBH7 is the mitochondrial AlkB family member that is required for alkylation-
and oxidation-induced programmed necrosis. In contrast to the protective role of
other AlkB family members after suffering alkylation-induced DNA damage, ALKBH7
triggers the collapse of mitochondrial membrane potential and promotes cell
death. Moreover, genetic ablation of mouse Alkbh7 dramatically increases body
weight and fat mass. Here, we present crystal structures of human ALKBH7 in
complex with Mn(II) and alpha-ketoglutarate at 1.35 A or N-oxalylglycine at 2.0 A
resolution. ALKBH7 possesses the conserved double-stranded beta-helix fold that
coordinates a catalytically active iron by a conserved HX(D/E) ... Xn ... H
motif. Self-hydroxylation of Leu-110 was observed, indicating that ALKBH7 has the
potential to catalyze hydroxylation of its substrate. Unlike other AlkB family
members whose substrates are DNA or RNA, ALKBH7 is devoid of the "nucleotide
recognition lid" which is essential for binding nucleobases, and thus exhibits a
solvent-exposed active site; two loops between beta-strands beta6 and beta7 and
between beta9 and beta10 create a special outer wall of the minor beta-sheet of
the double-stranded beta-helix and form a negatively charged groove. These
distinct features suggest that ALKBH7 may act on protein substrate rather than
nucleic acids. Taken together, our findings provide a structural basis for
understanding the distinct function of ALKBH7 in the AlkB family and offer a
foundation for drug design in treating cell death-related diseases and metabolic
diseases.
PMID- 25122758
TI - Electrostatic interactions in the binding pathway of a transient protein complex
studied by NMR and isothermal titration calorimetry.
AB - Much of our knowledge of protein binding pathways is derived from extremely
stable complexes that interact very tightly, with lifetimes of hours to days.
Much less is known about weaker interactions and transient complexes because
these are challenging to characterize experimentally. Nevertheless, these types
of interactions are ubiquitous in living systems. The combination of NMR
relaxation dispersion Carr-Purcell-Meiboom-Gill (CPMG) experiments and isothermal
titration calorimetry allows the quantification of rapid binding kinetics for
complexes with submillisecond lifetimes that are difficult to study using
conventional techniques. We have used this approach to investigate the binding
pathway of the Src homology 3 (SH3) domain from the Fyn tyrosine kinase, which
forms complexes with peptide targets whose lifetimes are on the order of about a
millisecond. Long range electrostatic interactions have been shown to play a
critical role in the binding pathways of tightly binding complexes. The role of
electrostatics in the binding pathways of transient complexes is less well
understood. Similarly to previously studied tight complexes, we find that SH3
domain association rates are enhanced by long range electrostatics, whereas short
range interactions are formed late in the docking process. However, the extent of
electrostatic association rate enhancement is several orders of magnitudes less,
whereas the electrostatic-free basal association rate is significantly greater.
Thus, the SH3 domain is far less reliant on electrostatic enhancement to achieve
rapid association kinetics than are previously studied systems. This suggests
that there may be overall differences in the role played by electrostatics in the
binding pathways of extremely stable versus transient complexes.
PMID- 25122759
TI - Stable single alpha-helices are constant force springs in proteins.
AB - Single alpha-helix (SAH) domains are rich in charged residues (Arg, Lys, and Glu)
and stable in solution over a wide range of pH and salt concentrations. They are
found in many different proteins where they bridge two functional domains. To
test the idea that their high stability might enable these proteins to resist
unfolding along their length, the properties and unfolding behavior of the
predicted SAH domain from myosin-10 were characterized. The expressed and
purified SAH domain was highly helical, melted non-cooperatively, and was
monomeric as shown by circular dichroism and mass spectrometry as expected for a
SAH domain. Single molecule force spectroscopy experiments showed that the SAH
domain unfolded at very low forces (<30 pN) without a characteristic unfolding
peak. Molecular dynamics simulations showed that the SAH domain unfolds
progressively as the length is increased and refolds progressively as the length
is reduced. This enables the SAH domain to act as a constant force spring in the
mechanically dynamic environment of the cell.
PMID- 25122760
TI - Activating transcription factor 3-mediated chemo-intervention with cancer
chemokines in a noncanonical pathway under endoplasmic reticulum stress.
AB - The cell-protective features of the endoplasmic reticulum (ER) stress response
are chronically activated in vigorously growing malignant tumor cells, which
provide cellular growth advantages over the adverse microenvironment including
chemotherapy. As an intervention with ER stress responses in the intestinal
cancer cells, preventive exposure to flavone apigenin potentiated superinduction
of a regulatory transcription factor, activating transcription factor 3 (ATF3),
which is also known to be an integral player coordinating ER stress response
related gene expression. ATF3 superinduction was due to increased turnover of
ATF3 transcript via stabilization with HuR protein in the cancer cells under ER
stress. Moreover, enhanced ATF3 caused inhibitory action against ER stress
induced cancer chemokines that are potent mediators determining the survival and
metastatic potential of epithelial cancer cells. Although enhanced ATF3 was a
negative regulator of the well known proinflammatory transcription factor NF
kappaB, blocking of NF-kappaB signaling did not affect ER stress-induced
chemokine expression. Instead, immediately expressed transcription factor early
growth response protein 1 (EGR-1) was positively involved in cancer chemokine
induction by ER stressors. ER stress-induced EGR-1 and subsequent chemokine
production were repressed by ATF3. Mechanistically, ATF3 directly interacted with
and recruited HDAC1 protein, which led to epigenetic suppression of EGR-1
expression and subsequent chemokine production. Conclusively, superinduced ATF3
attenuated ER stress-induced cancer chemokine expression by epigenetically
interfering with induction of EGR-1, a transcriptional modulator crucial to
cancer chemokine production. Thus, these results suggest a potent therapeutic
intervention of ER stress response-related cancer-favoring events by ATF3.
PMID- 25122761
TI - Group X secretory phospholipase A2 regulates insulin secretion through a
cyclooxygenase-2-dependent mechanism.
AB - Group X secretory phospholipase A2 (GX sPLA2) potently hydrolyzes membrane
phospholipids to release arachidonic acid (AA). While AA is an activator of
glucose-stimulated insulin secretion (GSIS), its metabolite prostaglandin E2
(PGE2) is a known inhibitor. In this study, we determined that GX sPLA2 is
expressed in insulin-producing cells of mouse pancreatic islets and investigated
its role in beta cell function. GSIS was measured in vivo in wild-type (WT) and
GX sPLA2-deficient (GX KO) mice and ex vivo using pancreatic islets isolated from
WT and GX KO mice. GSIS was also assessed in vitro using mouse MIN6 pancreatic
beta cells with or without GX sPLA2 overexpression or exogenous addition. GSIS
was significantly higher in islets isolated from GX KO mice compared with islets
from WT mice. Conversely, GSIS was lower in MIN6 cells overexpressing GX sPLA2
(MIN6-GX) compared with control (MIN6-C) cells. PGE2 production was significantly
higher in MIN6-GX cells compared with MIN6-C cells and this was associated with
significantly reduced cellular cAMP. The effect of GX sPLA2 on GSIS was abolished
when cells were treated with NS398 (a COX-2 inhibitor) or L-798,106 (a PGE2-EP3
receptor antagonist). Consistent with enhanced beta cell function, GX KO mice
showed significantly increased plasma insulin levels following glucose challenge
and were protected from age-related reductions in GSIS and glucose tolerance
compared with WT mice. We conclude that GX sPLA2 plays a previously unrecognized
role in negatively regulating pancreatic insulin secretion by augmenting COX-2
dependent PGE2 production.
PMID- 25122762
TI - Peroxiredoxin 4 improves insulin biosynthesis and glucose-induced insulin
secretion in insulin-secreting INS-1E cells.
AB - Oxidative folding of (pro)insulin is crucial for its assembly and biological
function. This process takes place in the endoplasmic reticulum (ER) and is
accomplished by protein disulfide isomerase and ER oxidoreductin 1beta,
generating stoichiometric amounts of hydrogen peroxide (H2O2) as byproduct.
During insulin resistance in the prediabetic state, increased insulin
biosynthesis can overwhelm the ER antioxidative and folding capacity, causing an
imbalance in the ER redox homeostasis and oxidative stress. Peroxiredoxin 4
(Prdx4), an ER-specific antioxidative peroxidase can utilize luminal H2O2 as
driving force for reoxidizing protein disulfide isomerase family members, thus
efficiently contributing to disulfide bond formation. Here, we examined the
functional significance of Prdx4 on beta-cell function with emphasis on insulin
content and secretion during stimulation with nutrient secretagogues.
Overexpression of Prdx4 in glucose-responsive insulin-secreting INS-1E cells
significantly metabolized luminal H2O2 and improved the glucose-induced insulin
secretion, which was accompanied by the enhanced proinsulin mRNA transcription
and insulin content. This beta-cell beneficial effect was also observed upon
stimulation with the nutrient insulin secretagogue combination of leucine plus
glutamine, indicating that the effect is not restricted to glucose. However,
knockdown of Prdx4 had no impact on H2O2 metabolism or beta-cell function due to
the fact that Prdx4 expression is negligibly low in pancreatic beta-cells.
Moreover, we provide evidence that the constitutively low expression of Prdx4 is
highly susceptible to hyperoxidation in the presence of high glucose. Overall,
these data suggest an important role of Prdx4 in maintaining insulin levels and
improving the ER folding capacity also under conditions of a high insulin
requirement.
PMID- 25122763
TI - Heat shock protein 83 (Hsp83) facilitates methoprene-tolerant (Met) nuclear
import to modulate juvenile hormone signaling.
AB - Juvenile hormone (JH) receptors, methoprene-tolerant (Met) and Germ-cell
expressed (Gce), transduce JH signals to induce Kr-h1 expression in Drosophila.
Dual luciferase assay identified a 120-bp JH response region (JHRR) in the Kr
h1alpha promoter. Both in vitro and in vivo experiments revealed that Met and Gce
transduce JH signals to induce Kr-h1 expression through the JHRR. DNA affinity
purification identified chaperone protein Hsp83 as one of the proteins bound to
the JHRR in the presence of JH. Interestingly, Hsp83 physically interacts with
PAS-B and basic helix-loop-helix domains of Met, and JH induces Met-Hsp83
interaction. As determined by immunohistochemistry, Met is mainly distributed in
the cytoplasm of fat body cells of the larval when the JH titer is low and JH
induces Met nuclear import. Hsp83 was accumulated in the cytoplasm area adjunct
to the nucleus in the presence of JH and Met/Gce. Loss-of-function of Hsp83
attenuated JH binding and JH-induced nuclear import of Met, resulting in a
decrease in the JHRR-driven reporter activity leading to reduction of Kr-h1
expression. These data show that Hsp83 facilitates the JH-induced nuclear import
of Met that induces Kr-h1 expression through the JHRR.
PMID- 25122764
TI - A pituitary homeobox 2 (Pitx2):microRNA-200a-3p:beta-catenin pathway converts
mesenchymal cells to amelogenin-expressing dental epithelial cells.
AB - Pitx2, Wnt/beta-catenin signaling, and microRNAs (miRs) play a critical role in
the regulation of dental stem cells during embryonic development. In this report,
we have identified a Pitx2:beta-catenin regulatory pathway involved in epithelial
cell differentiation and conversion of mesenchymal cells to amelogenin expressing
epithelial cells via miR-200a. Pitx2 and beta-catenin are expressed in the labial
incisor cervical loop or epithelial stem cell niche, with decreased expression in
the differentiating ameloblast cells of the mouse lower incisor. Bioinformatics
analyses reveal that miR-200a-3p expression is activated in the pre-ameloblast
cells to enhance epithelial cell differentiation. We demonstrate that Pitx2
activates miR-200a-3p expression and miR-200a-3p reciprocally represses Pitx2 and
beta-catenin expression. Pitx2 and beta-catenin interact to synergistically
activate gene expression during odontogenesis and miR-200a-3p attenuates their
expression and directs differentiation. To understand how this mechanism controls
cell differentiation and cell fate, oral epithelial and odontoblast mesenchymal
cells were reprogrammed by a two-step induction method using Pitx2 and miR-200a
3p. Conversion to amelogenin expressing dental epithelial cells involved an up
regulation of the stem cell marker Sox2 and proliferation genes and decreased
expression of mesenchymal markers. E-cadherin expression was increased as well as
ameloblast specific factors. The combination of Pitx2, a regulator of dental stem
cells and miR-200a converts mesenchymal cells to a fully differentiated dental
epithelial cell type. This pathway and reprogramming can be used to reprogram
mesenchymal or oral epithelial cells to dental epithelial (ameloblast) cells,
which can be used in tissue repair and regeneration studies.
PMID- 25122765
TI - Determinants of versican-V1 proteoglycan processing by the metalloproteinase
ADAMTS5.
AB - Proteolysis of the Glu(441)-Ala(442) bond in the glycosaminoglycan (GAG) beta
domain of the versican-V1 variant by a disintegrin-like and metalloproteinase
domain with thrombospondin type 1 motif (ADAMTS) proteases is required for proper
embryo morphogenesis. However, the processing mechanism and the possibility of
additional ADAMTS-cleaved processing sites are unknown. We demonstrate here that
if Glu(441) is mutated, ADAMTS5 cleaves inefficiently at a proximate upstream
site but normally does not cleave elsewhere within the GAGbeta domain.
Chondroitin sulfate (CS) modification of versican is a prerequisite for cleavage
at the Glu(441)-Ala(442) site, as demonstrated by reduced processing of CS
deficient or chondroitinase ABC-treated versican-V1. Site-directed mutagenesis
identified the N-terminal CS attachment sites Ser(507) and Ser(525) as essential
for processing of the Glu(441)-Ala(442) bond by ADAMTS5. A construct including
only these two GAG chains, but not downstream GAG attachment sites, was cleaved
efficiently. Therefore, CS chain attachment to Ser(507) and Ser(525) is necessary
and sufficient for versican proteolysis by ADAMTS5. Mutagenesis of Glu(441) and
an antibody to a peptide spanning Thr(432)-Gly(445) (i.e. containing the scissile
bond) reduced versican-V1 processing. ADAMTS5 lacking the C-terminal ancillary
domain did not cleave versican, and an ADAMTS5 ancillary domain construct bound
versican-V1 via the CS chains. We conclude that docking of ADAMTS5 with two N
terminal GAG chains of versican-V1 via its ancillary domain is required for
versican processing at Glu(441)-Ala(442). V1 proteolysis by ADAMTS1 demonstrated
a similar requirement for the N-terminal GAG chains and Glu(441). Therefore,
versican cleavage can be inhibited substantially by mutation of Glu(441),
Ser(507), and Ser(525) or by an antibody to the region of the scissile bond.
PMID- 25122766
TI - Myosin light chain kinase (MLCK) regulates cell migration in a myosin regulatory
light chain phosphorylation-independent mechanism.
AB - Myosin light chain kinase (MLCK) has long been implicated in the myosin
phosphorylation and force generation required for cell migration. Here, we
surprisingly found that the deletion of MLCK resulted in fast cell migration,
enhanced protrusion formation, and no alteration of myosin light chain
phosphorylation. The mutant cells showed reduced membrane tether force and fewer
membrane F-actin filaments. This phenotype was rescued by either kinase-dead MLCK
or five-DFRXXL motif, a MLCK fragment with potent F-actin-binding activity. Pull
down and co-immunoprecipitation assays showed that the absence of MLCK led to
attenuated formation of transmembrane complexes, including myosin II, integrins
and fibronectin. We suggest that MLCK is not required for myosin phosphorylation
in a migrating cell. A critical role of MLCK in cell migration involves
regulating the cell membrane tension and protrusion necessary for migration,
thereby stabilizing the membrane skeleton through F-actin-binding activity. This
finding sheds light on a novel regulatory mechanism of protrusion during cell
migration.
PMID- 25122767
TI - Hyaluronan breakdown contributes to immune defense against group A Streptococcus.
AB - Group A Streptococcus (GAS) commonly infects human skin and occasionally causes
severe and life-threatening invasive diseases. The hyaluronan (HA) capsule of GAS
has been proposed to protect GAS from host defense by mimicking endogenous HA, a
large and abundant glycosaminoglycan in the skin. However, HA is degraded during
tissue injury, and the functions of short-chain HA that is generated during
infection have not been studied. To examine the impact of the molecular mass of
HA on GAS infection, we established infection models in vitro and in vivo in
which the size of HA was defined by enzymatic digestion or custom synthesis. We
discovered that conversion of high molecular mass HA to low molecular mass HA
facilitated GAS phagocytosis by macrophages and limited the severity of infection
in mice. In contrast, native high molecular mass HA significantly impaired
internalization by macrophages and increased GAS survival in murine blood. Thus,
our data demonstrate that GAS virulence can be influenced by the size of HA
derived from both the bacterium and host and suggest that high molecular mass HA
facilitates GAS deep tissue infections, whereas the generation of short-chain HA
can be protective.
PMID- 25122768
TI - Thiosulfate transfer mediated by DsrE/TusA homologs from acidothermophilic sulfur
oxidizing archaeon Metallosphaera cuprina.
AB - Conserved clusters of genes encoding DsrE and TusA homologs occur in many
archaeal and bacterial sulfur oxidizers. TusA has a well documented function as a
sulfurtransferase in tRNA modification and molybdenum cofactor biosynthesis in
Escherichia coli, and DsrE is an active site subunit of the DsrEFH complex that
is essential for sulfur trafficking in the phototrophic sulfur-oxidizing
Allochromatium vinosum. In the acidothermophilic sulfur (S(0))- and tetrathionate
(S4O6(2-))-oxidizing Metallosphaera cuprina Ar-4, a dsrE3A-dsrE2B-tusA
arrangement is situated immediately between genes encoding dihydrolipoamide
dehydrogenase and a heterodisulfide reductase-like complex. In this study, the
biochemical features and sulfur transferring abilities of the DsrE2B, DsrE3A, and
TusA proteins were investigated. DsrE3A and TusA proved to react with
tetrathionate but not with NaSH, glutathione persulfide, polysulfide,
thiosulfate, or sulfite. The products were identified as protein-Cys-S
thiosulfonates. DsrE3A was also able to cleave the thiosulfate group from TusA
Cys(18)-S-thiosulfonate. DsrE2B did not react with any of the sulfur compounds
tested. DsrE3A and TusA interacted physically with each other and formed a
heterocomplex. The cysteine residue (Cys(18)) of TusA is crucial for this
interaction. The single cysteine mutants DsrE3A-C(93)S and DsrE3A-C(101)S
retained the ability to transfer the thiosulfonate group to TusA. TusA-C(18)S
neither reacted with tetrathionate nor was it loaded with thiosulfate with DsrE3A
Cys-S-thiosulfonate as the donor. The transfer of thiosulfate, mediated by a DsrE
like protein and TusA, is unprecedented not only in M. cuprina but also in other
sulfur-oxidizing prokaryotes. The results of this study provide new knowledge on
oxidative microbial sulfur metabolism.
PMID- 25122769
TI - Mitogen-activated protein kinase (MAPK)-regulated interactions between Osterix
and Runx2 are critical for the transcriptional osteogenic program.
AB - The transcription factors Runx2 and Osx (Osterix) are required for osteoblast
differentiation and bone formation. Runx2 expression occurs at early stages of
osteochondroprogenitor determination, followed by Osx induction during osteoblast
maturation. We demonstrate that coexpression of Osx and Runx2 leads to
cooperative induction of expression of the osteogenic genes Col1a1, Fmod, and
Ibsp. Functional interaction of Osx and Runx2 in the regulation of these
promoters is mediated by enhancer regions with adjacent Sp1 and Runx2 DNA-binding
sites. These enhancers allow formation of a cooperative transcriptional complex,
mediated by the binding of Osx and Runx2 to their specific DNA promoter sequences
and by the protein-protein interactions between them. We also identified the
domains involved in the interaction between Osx and Runx2. These regions contain
the amino acids in Osx and Runx2 known to be phosphorylated by p38 and ERK MAPKs.
Inhibition of p38 and ERK kinase activities or mutation of their known
phosphorylation sites in Osx or Runx2 strongly disrupts their physical
interaction and cooperative transcriptional effects. Altogether, our results
provide a molecular description of a mechanism for Osx and Runx2 transcriptional
cooperation that is subject to further regulation by MAPK-activating signals
during osteogenesis.
PMID- 25122771
TI - A distinct switch in interactions of the histone H4 tail domain upon salt
dependent folding of nucleosome arrays.
AB - The core histone tail domains mediate inter-nucleosomal interactions that direct
folding and condensation of nucleosome arrays into higher-order chromatin
structures. The histone H4 tail domain facilitates inter-array interactions by
contacting both the H2A/H2B acidic patch and DNA of neighboring nucleosomes.
Likewise, H4 tail-H2A contacts stabilize array folding. However, whether the H4
tail domains stabilize array folding via inter-nucleosomal interactions with the
DNA of neighboring nucleosomes remains unclear. We utilized defined
oligonucleosome arrays containing a single specialized nucleosome with a photo
inducible cross-linker in the N terminus of the H4 tail to characterize these
interactions. We observed that the H4 tail participates exclusively in intra
array interactions with DNA in unfolded arrays. These interactions are diminished
during array folding, yet no inter-nucleosome, intra-array H4 tail-DNA contacts
are observed in condensed chromatin. However, we document contacts between the N
terminus of the H4 tail and H2A. Installation of acetylation mimics known to
disrupt H4-H2A surface interactions did not increase observance of H4-DNA inter
nucleosomal interactions. These results suggest the multiple functions of the H4
tail require targeted distinct interactions within condensed chromatin.
PMID- 25122770
TI - Interaction with the Src homology (SH3-SH2) region of the Src-family kinase Hck
structures the HIV-1 Nef dimer for kinase activation and effector recruitment.
AB - HIV-1 Nef supports high titer viral replication in vivo and is essential for AIDS
progression. Nef function depends on interactions with multiple host cell
effectors, including Hck and other Src-family kinases. Here we describe the x-ray
crystal structure of Nef in complex with the Hck SH3-SH2 regulatory region to a
resolution of 1.86 A. The complex crystallized as a dimer of complexes, with the
conserved Nef PXXPXR motif engaging the Hck SH3 domain. A new intercomplex
contact was found between SH3 Glu-93, and Nef Arg-105. Mutagenesis of Hck SH3 Glu
93 interfered with Nef.Hck complex formation and kinase activation in cells. The
Hck SH2 domains impinge on the N-terminal region of Nef to stabilize a dimer
conformation that exposes Asp-123, a residue critical for Nef function. Our
results suggest that in addition to serving as a kinase effector for Nef, Hck
binding may reorganize the Nef dimer for functional interaction with other
signaling partners.
PMID- 25122772
TI - Inhibition of neuronal cell mitochondrial complex I with rotenone increases lipid
beta-oxidation, supporting acetyl-coenzyme A levels.
AB - Rotenone is a naturally occurring mitochondrial complex I inhibitor with a known
association with parkinsonian phenotypes in both human populations and rodent
models. Despite these findings, a clear mechanistic link between rotenone
exposure and neuronal damage remains to be determined. Here, we report
alterations to lipid metabolism in SH-SY5Y neuroblastoma cells exposed to
rotenone. The absolute levels of acetyl-CoA were found to be maintained despite a
significant decrease in glucose-derived acetyl-CoA. Furthermore, palmitoyl-CoA
levels were maintained, whereas the levels of many of the medium-chain acyl-CoA
species were significantly reduced. Additionally, using isotopologue analysis, we
found that beta-oxidation of fatty acids with varying chain lengths helped
maintain acetyl-CoA levels. Rotenone also induced increased glutamine utilization
for lipogenesis, in part through reductive carboxylation, as has been found
previously in other cell types. Finally, palmitoylcarnitine levels were increased
in response to rotenone, indicating an increase in fatty acid import. Taken
together, these findings show that alterations to lipid and glutamine metabolism
play an important compensatory role in response to complex I inhibition by
rotenone.
PMID- 25122773
TI - Inhibition of the functional interplay between endoplasmic reticulum (ER)
oxidoreduclin-1alpha (Ero1alpha) and protein-disulfide isomerase (PDI) by the
endocrine disruptor bisphenol A.
AB - Bisphenol A (BPA) is an endocrine disruptor that may have adverse effects on
human health. We recently isolated protein-disulfide isomerase (PDI) as a BPA
binding protein from rat brain homogenates and found that BPA markedly inhibited
PDI activity. To elucidate mechanisms of this inhibition, detailed structural,
biophysical, and functional analyses of PDI were performed in the presence of
BPA. BPA binding to PDI induced significant rearrangement of the N-terminal
thioredoxin domain of PDI, resulting in more compact overall structure. This
conformational change led to closure of the substrate-binding pocket in b'
domain, preventing PDI from binding to unfolded proteins. The b' domain also
plays an essential role in the interplay between PDI and ER oxidoreduclin 1alpha
(Ero1alpha), a flavoenzyme responsible for reoxidation of PDI. We show that BPA
inhibited Ero1alpha-catalyzed PDI oxidation presumably by inhibiting the
interaction between the b' domain of PDI and Ero1alpha; the phenol groups of BPA
probably compete with a highly conserved tryptophan residue, located in the
protruding beta-hairpin of Ero1alpha, for binding to PDI. Consistently, BPA
slowed down the reoxidation of PDI and caused the reduction of PDI in HeLa cells,
indicating that BPA has a great impact on the redox homeostasis of PDI within
cells. However, BPA had no effect on the interaction between PDI and
peroxiredoxin-4 (Prx4), another PDI family oxidase, suggesting that the
interaction between Prx4 and PDI is different from that of Ero1alpha and PDI.
These results indicate that BPA, a widely distributed and potentially harmful
chemical, inhibits Ero1-PDI-mediated disulfide bond formation.
PMID- 25122775
TI - HIV vaccine trial exploits a dual and central role for innate immunity.
AB - Limited understanding of correlates of protection from HIV transmission hinders
development of an efficacious vaccine. D. J. M. Lewis and colleagues (J. Virol.
88:11648-11657, 2014, doi:10.1128/JVI.01621-14) now report that vaginal
immunization with an HIVgp140 vaccine linked to the 70-kDa heat shock protein
downregulated the human immunodeficiency virus (HIV) coreceptor CCR5 (chemokine
[C-C motif] receptor 5) and increased expression of the HIV resistance factor
APOBEC3G (apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G),
in women. These effects correlated with HIV suppression ex vivo. Thus, vaccine
induced innate responses not only facilitate adaptive immunity-they may prove to
be critical for preventing HIV transmission.
PMID- 25122774
TI - 3,6,2',4',5'-Pentahydroxyflavone, an orally bioavailable multiple protein kinase
inhibitor, overcomes gefitinib resistance in non-small cell lung cancer.
AB - Non-small cell lung cancer (NSCLC) is the most lethal cancer, causing more than
150,000 deaths in the United States in 2013. The receptor tyrosine kinase
inhibitors such as gefitinib are not perfect clinical therapeutic agents for
NSCLC treatment due to primary or acquired tyrosine kinase inhibitor resistance.
Herein, 3,6,2',4',5'-pentahydroxyflavone (36245-PHF) was identified as a multiple
kinase inhibitor for NSCLC treatment based on the computational screening of a
natural products database. 36245-PHF was shown to inhibit PI3K and Aurora A and B
kinases and overcome gefitinib-resistant NSCLC growth. Our data clearly showed
that 36245-PHF markedly inhibited anchorage-independent growth of gefitinib
resistant NSCLC cell lines and exerted a substantial chemotherapeutic effect
following oral administration in a gefitinib-resistant NSCLC xenograft model. The
evidence from three different subsequent methodological approaches, in vitro, ex
vivo, and in vivo, all confirmed that 36245-PHF as a multiple protein kinase
inhibitor. Overall, we identified 36245-PHF as a multiple protein kinase
inhibitor and as a novel therapeutic agent to overcome gefitinib-resistant NSCLC
growth, which could provide a new option for clinical NSCLC oral treatment.
PMID- 25122777
TI - Type I interferon protects mice from fatal neurotropic infection with Langat
virus by systemic and local antiviral responses.
AB - Vector-borne flaviviruses, such as tick-borne encephalitis virus (TBEV), West
Nile virus, and dengue virus, cause millions of infections in humans. TBEV causes
a broad range of pathological symptoms, ranging from meningitis to severe
encephalitis or even hemorrhagic fever, with high mortality. Despite the
availability of an effective vaccine, the incidence of TBEV infections is
increasing. Not much is known about the role of the innate immune system in the
control of TBEV infections. Here, we show that the type I interferon (IFN) system
is essential for protection against TBEV and Langat virus (LGTV) in mice. In the
absence of a functional IFN system, mice rapidly develop neurological symptoms
and succumb to LGTV and TBEV infections. Type I IFN system deficiency results in
severe neuroinflammation in LGTV-infected mice, characterized by breakdown of the
blood-brain barrier and infiltration of macrophages into the central nervous
system (CNS). Using mice with tissue-specific IFN receptor deletions, we show
that coordinated activation of the type I IFN system in peripheral tissues as
well as in the CNS is indispensable for viral control and protection against
virus induced inflammation and fatal encephalitis. IMPORTANCE: The type I
interferon (IFN) system is important to control viral infections; however, the
interactions between tick-borne encephalitis virus (TBEV) and the type I IFN
system are poorly characterized. TBEV causes severe infections in humans that are
characterized by fever and debilitating encephalitis, which can progress to
chronic illness or death. No treatment options are available. An improved
understanding of antiviral innate immune responses is pivotal for the development
of effective therapeutics. We show that type I IFN, an effector molecule of the
innate immune system, is responsible for the extended survival of TBEV and Langat
virus (LGTV), an attenuated member of the TBE serogroup. IFN production and
signaling appeared to be essential in two different phases during infection. The
first phase is in the periphery, by reducing systemic LGTV replication and
spreading into the central nervous system (CNS). In the second phase, the local
IFN response in the CNS prevents virus-induced inflammation and the development
of encephalitis.
PMID- 25122776
TI - Increased replicative fitness can lead to decreased drug sensitivity of hepatitis
C virus.
AB - Passage of hepatitis C virus (HCV) in human hepatoma cells resulted in
populations that displayed partial resistance to alpha interferon (IFN-alpha),
telaprevir, daclatasvir, cyclosporine, and ribavirin, despite no prior exposure
to these drugs. Mutant spectrum analyses and kinetics of virus production in the
absence and presence of drugs indicate that resistance is not due to the presence
of drug resistance mutations in the mutant spectrum of the initial or passaged
populations but to increased replicative fitness acquired during passage. Fitness
increases did not alter host factors that lead to shutoff of general host cell
protein synthesis and preferential translation of HCV RNA. The results imply that
viral replicative fitness is a mechanism of multidrug resistance in HCV.
Importance: Viral drug resistance is usually attributed to the presence of amino
acid substitutions in the protein targeted by the drug. In the present study with
HCV, we show that high viral replicative fitness can confer a general drug
resistance phenotype to the virus. The results exclude the possibility that
genomes with drug resistance mutations are responsible for the observed
phenotype. The fact that replicative fitness can be a determinant of multidrug
resistance may explain why the virus is less sensitive to drug treatments in
prolonged chronic HCV infections that favor increases in replicative fitness.
PMID- 25122778
TI - Computational prediction of vaccine strains for human influenza A (H3N2) viruses.
AB - Human influenza A viruses are rapidly evolving pathogens that cause substantial
morbidity and mortality in seasonal epidemics around the globe. To ensure
continued protection, the strains used for the production of the seasonal
influenza vaccine have to be regularly updated, which involves data collection
and analysis by numerous experts worldwide. Computer-guided analysis is becoming
increasingly important in this problem due to the vast amounts of generated data.
We here describe a computational method for selecting a suitable strain for
production of the human influenza A virus vaccine. It interprets available
antigenic and genomic sequence data based on measures of antigenic novelty and
rate of propagation of the viral strains throughout the population. For viral
isolates sampled between 2002 and 2007, we used this method to predict the
antigenic evolution of the H3N2 viruses in retrospective testing scenarios. When
seasons were scored as true or false predictions, our method returned six true
positives, three false negatives, eight true negatives, and one false positive,
or 78% accuracy overall. In comparison to the recommendations by the WHO, we
identified the correct antigenic variant once at the same time and twice one
season ahead. Even though it cannot be ruled out that practical reasons such as
lack of a sufficiently well-growing candidate strain may in some cases have
prevented recommendation of the best-matching strain by the WHO, our
computational decision procedure allows quantitative interpretation of the
growing amounts of data and may help to match the vaccine better to predominating
strains in seasonal influenza epidemics. Importance: Human influenza A viruses
continuously change antigenically to circumvent the immune protection evoked by
vaccination or previously circulating viral strains. To maintain vaccine
protection and thereby reduce the mortality and morbidity caused by infections,
regular updates of the vaccine strains are required. We have developed a data
driven framework for vaccine strain prediction which facilitates the
computational analysis of genetic and antigenic data and does not rely on
explicit evolutionary models. Our computational decision procedure generated good
matches of the vaccine strain to the circulating predominant strain for most
seasons and could be used to support the expert-guided prediction made by the
WHO; it thus may allow an increase in vaccine efficacy.
PMID- 25122780
TI - Core-binding factor subunit beta is not required for non-primate lentiviral Vif
mediated APOBEC3 degradation.
AB - Viral infectivity factor (Vif) is required for lentivirus fitness and
pathogenicity, except in equine infectious anemia virus (EIAV). Vif enhances
viral infectivity by a Cullin5-Elongin B/C E3 complex to inactivate the host
restriction factor APOBEC3. Core-binding factor subunit beta (CBF-beta) is a cell
factor that was recently shown to be important for the primate lentiviral Vif
function. Non-primate lentiviral Vif also degrades APOBEC3 through the proteasome
pathway. However, it is unclear whether CBF-beta is required for the non-primate
lentiviral Vif function. In this study, we demonstrated that the Vifs of non
primate lentiviruses, including feline immunodeficiency virus (FIV), bovine
immunodeficiency virus (BIV), caprine arthritis encephalitis virus (CAEV), and
maedi-visna virus (MVV), do not interact with CBF-beta. In addition, CBF-beta did
not promote the stability of FIV, BIV, CAEV, and MVV Vifs. Furthermore, CBF-beta
silencing or overexpression did not affect non-primate lentiviral Vif-mediated
APOBEC3 degradation. Our results suggest that non-primate lentiviral Vif induces
APOBEC3 degradation through a different mechanism than primate lentiviral Vif.
Importance: The APOBEC3 protein family members are host restriction factors that
block retrovirus replication. Vif, an accessory protein of lentivirus, degrades
APOBEC3 to rescue viral infectivity by forming Cullin5-Elongin B/C-based E3
complex. CBF-beta was proved to be a novel regulator of primate lentiviral Vif
function. In this study, we found that CBF-beta knockdown or overexpression did
not affect FIV Vif's function, which induced polyubiquitination and degradation
of APOBEC3 by recruiting the E3 complex in a manner similar to that of HIV-1 Vif.
We also showed that other non-primate lentiviral Vifs did not require CBF-beta to
degrade APOBEC3. CBF-beta did not interact with non-primate lentiviral Vifs or
promote their stability. These results suggest that a different mechanism exists
for the Vif-APOBEC interaction and that non-primates are not suitable animal
models for exploring pharmacological interventions that disrupt Vif-CBF-beta
interaction.
PMID- 25122779
TI - Modulation of hepatitis C virus genome replication by glycosphingolipids and four
phosphate adaptor protein 2.
AB - Hepatitis C virus (HCV) assembles its replication complex on cytosolic membrane
vesicles often clustered in a membranous web (MW). During infection, HCV NS5A
protein activates PI4KIIIalpha enzyme, causing massive production and
redistribution of phosphatidylinositol 4-phosphate (PI4P) lipid to the
replication complex. However, the role of PI4P in the HCV life cycle is not well
understood. We postulated that PI4P recruits host effectors to modulate HCV
genome replication or virus particle production. To test this hypothesis, we
generated cell lines for doxycycline-inducible expression of short hairpin RNAs
(shRNAs) targeting the PI4P effector, four-phosphate adaptor protein 2 (FAPP2).
FAPP2 depletion attenuated HCV infectivity and impeded HCV RNA synthesis. Indeed,
FAPP2 has two functional lipid-binding domains specific for PI4P and
glycosphingolipids. While expression of the PI4P-binding mutant protein was
expected to inhibit HCV replication, a marked drop in replication efficiency was
observed unexpectedly with the glycosphingolipid-binding mutant protein. These
data suggest that both domains are crucial for the role of FAPP2 in HCV genome
replication. We also found that HCV significantly increases the level of some
glycosphingolipids, whereas adding these lipids to FAPP2-depleted cells partially
rescued replication, further arguing for the importance of glycosphingolipids in
HCV RNA synthesis. Interestingly, FAPP2 is redistributed to the replication
complex (RC) characterized by HCV NS5A, NS4B, or double-stranded RNA (dsRNA)
foci. Additionally, FAPP2 depletion disrupts the RC and alters the colocalization
of HCV replicase proteins. Altogether, our study implies that HCV coopts FAPP2
for virus genome replication via PI4P binding and glycosphingolipid transport to
the HCV RC. IMPORTANCE: Like most viruses with a positive-sense RNA genome, HCV
replicates its RNA on remodeled host membranes composed of lipids hijacked from
various internal membrane compartments. During infection, HCV induces massive
production and retargeting of the PI4P lipid to its replication complex. However,
the role of PI4P in HCV replication is not well understood. In this study, we
have shown that FAPP2, a PI4P effector and glycosphingolipid-binding protein, is
recruited to the HCV replication complex and is required for HCV genome
replication and replication complex formation. More importantly, this study
demonstrates, for the first time, the crucial role of glycosphingolipids in the
HCV life cycle and suggests a link between PI4P and glycosphingolipids in HCV
genome replication.
PMID- 25122781
TI - Emergence of broadly neutralizing antibodies and viral coevolution in two
subjects during the early stages of infection with human immunodeficiency virus
type 1.
AB - Delineating the key early events that lead to the development of broadly
neutralizing anti-HIV-1 antibodies during natural infection may help guide the
development of immunogens and vaccine regimens to prevent HIV-1 infection. In
this study, we monitored two HIV-1-positive subjects, VC20013 and VC10014, over
the course of infection from before they developed broadly neutralizing antibody
(bNAb) activity until several years after neutralizing breadth was detected in
plasma. Both subjects developed bNAb activity after approximately 1 year
postinfection, which ultimately mapped to the membrane-proximal external region
(MPER) in VC20013 and an epitope that overlaps the CD4 receptor binding site in
VC10014. In subject VC20013, we were able to identify anti-MPER activity in the
earliest plasma sample that exhibited no bNAb activity, indicating that this
epitope specificity was acquired very early on, but that it was initially not
able to mediate neutralization. Escape mutations within the bNAb epitopes did not
arise in the circulating envelopes until bNAb activity was detectable in plasma,
indicating that this early response was not sufficient to drive viral escape. As
bNAb activity began to emerge in both subjects, we observed a simultaneous
increase in autologous antienvelope antibody binding affinity, indicating that
antibody maturation was occurring as breadth was developing. Our findings
illustrate one potential mechanism by which bNAbs develop during natural
infection in which an epitope target is acquired very early on during the course
of infection but require time and maturation to develop into broadly neutralizing
activity. IMPORTANCE: One major goal of HIV-1 vaccine research is the development
of a vaccine that can elicit broadly neutralizing antibodies (bNAbs). Although no
such vaccine exists, bNAbs develop in approximately 20% of HIV-1-infected
subjects, providing a prototype of the bNAbs that must be reelicited by vaccine.
Thus, there is significant interest in understanding the mechanisms by which
bNAbs develop during the course of infection. We studied the timing, epitope
specificity, and evolution of the bNAb responses in two HIV-1-positive patients
who developed bNAb activity within the first several years after infection. In
one subject, antibodies to a broadly neutralizing epitope developed very early
but were nonneutralizing. After several months, neutralizing activity developed,
and the virus mutated to escape their activity. Our study highlights one
mechanism for the development of bNAbs where early epitope acquisition followed
by sufficient time for antibody maturation drives the epitope-specific antibody
response toward broadly neutralizing activity.
PMID- 25122782
TI - Probing the functions of the paramyxovirus glycoproteins F and HN with a panel of
synthetic antibodies.
AB - Paramyxoviruses are enveloped negative-strand RNA viruses that are significant
human and animal pathogens. Most paramyxoviruses infect host cells via the
concerted action of a tetrameric attachment protein (variously called HN, H, or
G) that binds either sialic acid or protein receptors on target cells and a
trimeric fusion protein (F) that merges the viral envelope with the plasma
membrane at neutral pH. F initially folds to a metastable prefusion conformation
that becomes activated via a cleavage event during cellular trafficking. Upon
receptor binding, the attachment protein, which consists of a globular head
anchored to the membrane via a helical tetrameric stalk, triggers a major
conformation change in F which results in fusion of virus and host cell
membranes. We recently proposed a model for F activation in which the attachment
protein head domains move following receptor binding to expose HN stalk residues
critical for triggering F. To test the model in the context of wild-type viral
glycoproteins, we used a restricted-diversity combinatorial Fab library and phage
display to rapidly generate synthetic antibodies (sAbs) against multiple domains
of the paramyxovirus parainfluenza 5 (PIV5) pre- and postfusion F and HN. As
predicted by the model, sAbs that bind to the critical F-triggering region of the
HN stalk do not disrupt receptor binding or neuraminidase (NA) activity but are
potent inhibitors of fusion. An inhibitory prefusion F-specific sAb recognized a
quaternary antigenic site and may inhibit fusion by preventing F refolding or by
blocking the F-HN interaction. Importance: The paramyxovirus family of negative
strand RNA viruses cause significant disease in humans and animals. The viruses
bind to cells via their receptor binding protein and then enter cells by fusion
of their envelope with the host cell plasma membrane, a process mediated by a
metastable viral fusion (F) protein. To understand the steps in viral membrane
fusion, a library of synthetic antibodies to F protein and the receptor binding
protein was generated in bacteriophage. These antibodies bound to different
regions of the F protein and the receptor binding protein, and the location of
antibody binding affected different processes in viral entry into cells.
PMID- 25122783
TI - Visualization of retroviral envelope spikes in complex with the V3 loop antibody
447-52D on intact viruses by cryo-electron tomography.
AB - The gp120 portion of the envelope spike on human immunodeficiency virus type 1
(HIV-1) plays a critical role in viral entry into host cells and is a key target
for the humoral immune response, and yet many structural details remain elusive.
We have used cryoelectron tomography to visualize the binding of the broadly
neutralizing monoclonal antibody (MAb) 447-52D to intact envelope spikes on
virions of HIV-1 MN strain. Antibody 447-52D has previously been shown to bind to
the tip of the V3 loop. Our results show antibody arms radiating from the sides
of the gp120 protomers at a range of angles and place the antibody-bound V3 loop
in an orientation that differs from that predicted by most current models but
consistent with the idea that antibody binding dislodges the V3 loop from its
location in the Env spike, making it flexible and disordered. These data reveal
information on the position of the V3 loop and its relative flexibility and
suggest that 447-52D neutralizes HIV-1 MN by capturing the V3 loop, blocking its
interaction with the coreceptor and altering the structure of the envelope spike.
IMPORTANCE: Antibody neutralization is one of the primary ways that the body
fights infection with HIV. Because HIV is a highly mutable virus, the body must
constantly produce new antibodies to counter new strains of HIV that the body
itself is producing. Consequently, antibodies capable of neutralizing multiple
HIV strains are comparatively few. An improved understanding of the mechanism of
antibody neutralization might advance the development of immunogens. Most
neutralizing antibodies target the Env glycoprotein spikes found on the virus
surface. The broadly neutralizing antibody 447-52D targets the highly conserved
beta-turn of variable loop 3 (V3) of gp120. The importance of V3 lies in its
contribution to the coreceptor binding site on the target cell. We show here that
447-52D binding to V3 converts the Env conformation from closed to open and makes
the V3 loop highly flexible, implying disruption of coreceptor binding and
attachment to the target cell.
PMID- 25122784
TI - Equine viperin restricts equine infectious anemia virus replication by inhibiting
the production and/or release of viral Gag, Env, and receptor via distortion of
the endoplasmic reticulum.
AB - Viperin is an endoplasmic reticulum (ER)-associated multifunctional protein that
regulates virus replication and possesses broad antiviral activity. In many
cases, viperin interferes with the trafficking and budding of viral structural
proteins by distorting the membrane transportation system. The lentivirus equine
infectious anemia virus (EIAV) has been studied extensively. In this study, we
examined the restrictive effect of equine viperin (eViperin) on EIAV replication
and investigated the possible molecular basis of this restriction to obtain
insights into the effect of this cellular factor on retroviruses. We demonstrated
that EIAV infection of primary equine monocyte-derived macrophages (eMDMs)
upregulated the expression of eViperin. The overexpression of eViperin
significantly inhibited the replication of EIAV in eMDMs, and knockdown of
eViperin transcription enhanced the replication of EIAV in eMDMs by approximately
45.8%. Further experiments indicated that eViperin restricts EIAV at multiple
steps of viral replication. The overexpression of eViperin inhibited EIAV Gag
release. Both the alpha-helix domain and radical S-adenosylmethionine (SAM)
domain were required for this activity. However, the essential motifs in SAM were
different from those reported for the inhibition of HIV-1 Gag by human viperin.
Furthermore, eViperin disrupted the synthesis of both EIAV Env and receptor,
which consequently inhibited viral production and entry, respectively, and this
disruption was dependent on the eViperin alpha-helix domain. Using
immunofluorescence assays and electron microscopy, we demonstrated that the alpha
helix domain is responsible for the distortion of the endoplasmic reticulum (ER).
Finally, EIAV did not exhibit counteracting eViperin at the protein level.
IMPORTANCE: In previous studies, viperin was indicated as restricting virus
replications primarily by the inhibition of virus budding. Here, we show that
viperin may have multiple antiviral mechanisms, including the reduction of EIAV
Gag budding and Env expression, and these activities are dependent on different
viperin domains. We especially demonstrate that the overexpression of viperin
inhibits EIAV entry by decreasing the level of virus receptor. Therefore, viperin
restriction of viruses is determined largely by the dependence of virus on the
cellular membrane transportation system.
PMID- 25122785
TI - Cross-clade ultrasensitive PCR-based assays to measure HIV persistence in large
cohort studies.
AB - A small pool of infected cells persists in HIV-infected individuals receiving
antiretroviral therapy (ART). Here, we developed ultrasensitive assays to
precisely measure the frequency of cells harboring total HIV DNA, integrated HIV
DNA, and two long terminal repeat (2-LTR) circles. These assays are performed on
cell lysates, which circumvents the labor-intensive step of DNA extraction, and
rely on the coquantification of each HIV molecular form together with CD3 gene
sequences to precisely measure cell input. Using primary isolates from HIV
subtypes A, B, C, D, and CRF01_A/E, we demonstrate that these assays can
efficiently quantify low target copy numbers from diverse HIV subtypes. We
further used these assays to measure total HIV DNA, integrated HIV DNA, and 2-LTR
circles in CD4(+) T cells from HIV-infected subjects infected with subtype B. All
samples obtained from ART-naive subjects were positive for the three HIV
molecular forms (n = 15). Total HIV DNA, integrated HIV DNA, and 2-LTR circles
were detected in, respectively, 100%, 94%, and 77% of the samples from
individuals in which HIV was suppressed by ART. Higher levels of total HIV DNA
and 2-LTR circles were detected in untreated subjects than individuals on ART (P
= 0.0003 and P = 0.0004, respectively), while the frequency of CD4(+) T cells
harboring integrated HIV DNA did not differ between the two groups. These results
demonstrate that these novel assays have the ability to quantify very low levels
of HIV DNA of multiple HIV subtypes without the need for nucleic acid extraction,
making them well suited for the monitoring of viral persistence in large
populations of HIV-infected individuals. IMPORTANCE: Since the discovery of viral
reservoirs in HIV-infected subjects receiving suppressive ART, measuring the
degree of viral persistence has been one of the greatest challenges in the field
of HIV research. Here, we report the development and validation of ultrasensitive
assays to measure HIV persistence in HIV-infected individuals from multiple
geographical regions. These assays are relatively inexpensive, do not require DNA
extraction, and can be completed in a single day. Therefore, they are perfectly
adapted to monitor HIV persistence in large cohorts of HIV-infected individuals
and, given their sensitivity, can be used to monitor the efficacy of therapeutic
strategies aimed at interfering with HIV persistence after prolonged ART.
PMID- 25122787
TI - The N terminus of the influenza B virus nucleoprotein is essential for virus
viability, nuclear localization, and optimal transcription and replication of the
viral genome.
AB - The nucleoprotein (NP) of influenza viruses is a multifunctional protein with
essential roles throughout viral replication. Despite influenza A and B viruses
belonging to separate genera of the Orthomyxoviridae family, their NP proteins
share a relatively high level of sequence conservation. However, NP of influenza
B viruses (BNP) contains an evolutionarily conserved N-terminal 50-amino-acid
extension that is absent from NP of influenza A viruses. There is conflicting
evidence as to the functions of the BNP N-terminal extension; however, this has
never been assessed in the context of viral infection. We have used reverse
genetics to assess the significance of this region on the functions of BNP and
virus viability. The truncation of more than three amino acids prevented virus
recovery, suggesting that the N-terminal extension is essential for virus
viability. Mutational analysis indicated that multiple regions of the protein are
involved in the nuclear localization of BNP, with the entire N-terminal extension
required for this to function efficiently. Viruses containing mutations in the
first 10 residues of BNP demonstrated few differences in nuclear localization;
however, the viruses exhibited significant reductions in viral mRNA transcription
and genome replication, resulting in significantly attenuated phenotypes.
Mutations introduced to ablate a previously reported nuclear localization signal
also resulted in a significant decrease in mRNA production during early stages of
viral replication. Overall, our results demonstrate that the N-terminal extension
of BNP is essential to virus viability not only for directing nuclear
localization of BNP but also for regulating viral mRNA transcription and genome
replication. IMPORTANCE: The multifunctional NP of influenza viruses has roles
throughout the viral replication cycle; therefore, it is essential for virus
viability. Despite high levels of homology between the NP of influenza A and B
viruses, the NP of influenza B virus contains an evolutionarily conserved 50
amino-acid N-terminal extension that is absent from the NP of influenza A
viruses. In this study, we show that this N-terminal extension is essential for
virus viability, and we confirm and expand upon recent findings that this region
of BNP is required for nuclear localization of the protein. Furthermore, we
demonstrate for the first time that the N terminus of BNP is involved in
regulating viral mRNA transcription and replication of the viral genome. As the
NP of influenza A virus lacks this N-terminal extension, these viruses may have
evolved separate mechanisms to regulate these processes.
PMID- 25122786
TI - The temperature-sensitive and attenuation phenotypes conferred by mutations in
the influenza virus PB2, PB1, and NP genes are influenced by the species of
origin of the PB2 gene in reassortant viruses derived from influenza
A/California/07/2009 and A/WSN/33 viruses.
AB - Live attenuated influenza vaccines in the United States are derived from a human
virus that is temperature sensitive (ts), characterized by restricted (>= 100
fold) replication at 39 degrees C. The ts genetic signature (ts sig) has been
mapped to 5 loci in 3 genes: PB1 (391 E, 581 G, and 661 T), PB2 (265 S), and NP
(34 G). However, when transferred into avian and swine influenza viruses, only
partial ts and attenuation phenotypes occur. To investigate the reason for this,
we introduced the ts sig into the human origin virus A/WSN/33 (WSN), the avian
origin virus A/Vietnam/1203/04 (VN04), and the swine origin triple-reassortant
2009 pandemic H1N1 virus A/California/07/2009 (CA07), which contains gene
segments from human, avian, and swine viruses. The VN04(ts sig) and CA07(ts sig)
viruses replicated efficiently in Madin-Darby canine kidney (MDCK) cells at 39
degrees C, but the replication of WSN(ts sig) was restricted >= 100-fold compared
to that at 33 degrees C. Reassortant CA07(ts sig) viruses were generated with
individual polymerase gene segments from WSN, and vice versa. Only ts sig viruses
with a PB2 gene segment derived from WSN were restricted in replication >= 100
fold at 39 degrees C. In ferrets, the CA07(ts sig) virus replicated in the upper
and lower respiratory tract, but the replication of a reassortant CA07(ts sig)
virus with a WSN PB2 gene was severely restricted in the lungs. Taken together,
these data suggest that the origin of the PB2 gene segment influences the ts
phenotype in vitro and attenuation in vivo. This could have implications for the
design of novel live vaccines against animal origin influenza viruses.
IMPORTANCE: Live attenuated influenza vaccines (LAIVs) on temperature-sensitive
(ts) backbones derived from animal origin influenza viruses are being sought for
use in the poultry and swine industries and to protect people against animal
origin influenza. However, inserting the ts genetic signature from a licensed
LAIV backbone fails to fully attenuate these viruses. Our data indicate this is
associated with the presence of a PB2 gene segment derived from an avian
influenza virus. We show that a reassortant 2009 pandemic H1N1 virus with the ts
signature from a licensed LAIV donor virus is ts in vitro and attenuated in vivo
when the PB2 gene is derived from a human origin virus but not from an avian
virus. Our study provides information that could benefit the rational design of
alternative LAIV backbones against animal origin influenza viruses.
PMID- 25122788
TI - Epitope mapping of the hemagglutinin molecule of A/(H1N1)pdm09 influenza virus by
using monoclonal antibody escape mutants.
AB - We determined the antigenic structure of pandemic influenza A(H1N1)pdm09 virus
hemagglutinin (HA) using 599 escape mutants that were selected using 16 anti-HA
monoclonal antibodies (MAbs) against A/Narita/1/2009. The sequencing of mutant HA
genes revealed 43 amino acid substitutions at 24 positions in three antigenic
sites, Sa, Sb, and Ca2, which were previously mapped onto A/Puerto Rico/8/34
(A/PR/8/34) HA (A. J. Caton, G. G. Brownlee, J. W. Yewdell, and W. Gerhard, Cell
31:417-427, 1982), and an undesignated site, i.e., amino acid residues 141, 142,
143, 171, 172, 174, 177, and 180 in the Sa site, residues 170, 173, 202, 206,
210, 211, and 212 in the Sb site, residues 151, 154, 156, 157, 158, 159, 200, and
238 in the Ca2 site, and residue 147 in the undesignated site (numbering begins
at the first methionine). Sixteen MAbs were classified into four groups based on
their cross-reactivity with the panel of escape mutants in the hemagglutination
inhibition test. Among them, six MAbs targeting the Sa and Sb sites recognized
both residues at positions 172 and 173. MAb n2 lost reactivity when mutations
were introduced at positions 147, 159 (site Ca2), 170 (site Sb), and 172 (site
Sa). We designated the site consisting of these residues as site Pa. From 2009 to
2013, no antigenic drift was detected for the A(H1N1)pdm09 viruses. However, if a
novel variant carrying a mutation at a position involved in the epitopes of
several MAbs, such as 172, appeared, such a virus would have the advantage of
becoming a drift strain. IMPORTANCE: The first influenza pandemic of the 21st
century occurred in 2009 with the emergence of a novel virus originating with
swine influenza, A(H1N1)pdm09. Although HA of A(H1N1)pdm09 has a common origin
(1918 H1N1) with seasonal H1N1, the antigenic divergence of HA between the
seasonal H1N1 and A(H1N1)pdm09 viruses gave rise to the influenza pandemic in
2009. To take precautions against the antigenic drift of the A(H1N1)pdm09 virus
in the near future, it is important to identify its precise antigenic structure.
To obtain various mutants that are not neutralized by MAbs, it is important to
neutralize several plaque-cloned parent viruses rather than only a single parent
virus. We characterized 599 escape mutants that were obtained by neutralizing
four parent viruses of A(H1N1)pdm09 in the presence of 16 MAbs. Consequently, we
were able to determine the details of the antigenic structure of HA, including a
novel epitope.
PMID- 25122789
TI - The matrix gene segment destabilizes the acid and thermal stability of the
hemagglutinin of pandemic live attenuated influenza virus vaccines.
AB - The threat of future influenza pandemics and their potential for rapid spread,
morbidity, and mortality has led to the development of pandemic vaccines. We
generated seven reassortant pandemic live attenuated influenza vaccines (pLAIVs)
with the hemagglutinin (HA) and neuraminidase (NA) genes derived from animal
influenza viruses on the backbone of the six internal protein gene segments of
the temperature sensitive, cold-adapted (ca) A/Ann Arbor/60 (H2N2) virus (AA/60
ca) of the licensed seasonal LAIV. The pLAIV viruses were moderately to highly
restricted in replication in seronegative adults; we sought to determine the
biological basis for this restriction. Avian influenza viruses generally
replicate at higher temperatures than human influenza viruses and, although they
shared the same backbone, the pLAIV viruses had a lower shutoff temperature than
seasonal LAIV viruses, suggesting that the HA and NA influence the degree of
temperature sensitivity. The pH of HA activation of highly pathogenic avian
influenza viruses was greater than human and low-pathogenicity avian influenza
viruses, as reported by others. However, pLAIV viruses had a consistently higher
pH of HA activation and reduced HA thermostability compared to the corresponding
wild-type parental viruses. From studies with single-gene reassortant viruses
bearing one gene segment from the AA/60 ca virus in recombinant H5N1 or pH1N1
viruses, we found that the lower HA thermal stability and increased pH of HA
activation were associated with the AA/60 M gene. Together, the impaired HA acid
and thermal stability and temperature sensitivity likely contributed to the
restricted replication of the pLAIV viruses we observed in seronegative adults.
IMPORTANCE: There is increasing evidence that the HA stability of influenza
viruses depends on the virus strain and host species and that HA stability can
influence replication, virulence, and transmission of influenza A viruses in
different species. We investigated the HA stability of pandemic live attenuated
influenza vaccine (pLAIV) viruses and observed that the pLAIV viruses
consistently had a less stable HA than the corresponding wild-type influenza
viruses. The reduced HA stability and temperature sensitivity of the pLAIV
viruses may account for their restricted replication in clinical trials.
PMID- 25122791
TI - Stearoyl coenzyme A desaturase 1 is associated with hepatitis C virus replication
complex and regulates viral replication.
AB - The hepatitis C virus (HCV) life cycle is tightly regulated by lipid metabolism
of host cells. In order to identify host factors involved in HCV propagation, we
have recently screened a small interfering RNA (siRNA) library targeting host
genes that control lipid metabolism and lipid droplet formation using cell
culture-grown HCV (HCVcc)-infected cells. We selected and characterized the gene
encoding stearoyl coenzyme A (CoA) desaturase 1 (SCD1). siRNA-mediated knockdown
or pharmacological inhibition of SCD1 abrogated HCV replication in both
subgenomic replicon and Jc1-infected cells, while exogenous supplementation of
either oleate or palmitoleate, products of SCD1 activity, resurrected HCV
replication in SCD1 knockdown cells. SCD1 was coimmunoprecipitated with HCV
nonstructural proteins and colocalized with both double-stranded RNA (dsRNA) and
HCV nonstructural proteins, indicating that SCD1 is associated with HCV
replication complex. Moreover, SCD1 was fractionated and enriched with HCV
nonstructural proteins at detergent-resistant membrane. Electron microscopy data
showed that SCD1 is required for NS4B-mediated intracellular membrane
rearrangement. These data further support the idea that SCD1 is associated with
HCV replication complex and that its products may contribute to the proper
formation and maintenance of membranous web structures in HCV replication
complex. Collectively, these data suggest that manipulation of SCD1 activity may
represent a novel host-targeted antiviral strategy for the treatment of HCV
infection. IMPORTANCE: Stearoyl coenzyme A (CoA) desaturase 1 (SCD1), a liver
specific enzyme, regulates hepatitis C virus (HCV) replication through its enzyme
activity. HCV nonstructural proteins are associated with SCD1 at detergent
resistant membranes, and SCD1 is enriched on the lipid raft by HCV infection.
Therein, SCD1 supports NS4B-mediated membrane rearrangement to provide a suitable
microenvironment for HCV replication. We demonstrated that either genetic or
chemical knockdown of SCD1 abrogated HCV replication in both replicon cells and
HCV-infected cells. These findings provide novel mechanistic insights into the
roles of SCD1 in HCV replication.
PMID- 25122790
TI - Methyltransferase-defective avian metapneumovirus vaccines provide complete
protection against challenge with the homologous Colorado strain and the
heterologous Minnesota strain.
AB - Avian metapneumovirus (aMPV), also known as avian pneumovirus or turkey
rhinotracheitis virus, is the causative agent of turkey rhinotracheitis and is
associated with swollen head syndrome in chickens. Since its discovery in the
1970s, aMPV has been recognized as an economically important pathogen in the
poultry industry worldwide. The conserved region VI (CR VI) of the large (L)
polymerase proteins of paramyxoviruses catalyzes methyltransferase (MTase)
activities that typically methylate viral mRNAs at guanine N-7 (G-N-7) and ribose
2'-O positions. In this study, we generated a panel of recombinant aMPV (raMPV)
Colorado strains carrying mutations in the S-adenosyl methionine (SAM) binding
site in the CR VI of L protein. These recombinant viruses were specifically
defective in ribose 2'-O, but not G-N-7 methylation and were genetically stable
and highly attenuated in cell culture and viral replication in the upper and
lower respiratory tracts of specific-pathogen-free (SPF) young turkeys.
Importantly, turkeys vaccinated with these MTase-defective raMPVs triggered a
high level of neutralizing antibody and were completely protected from challenge
with homologous aMPV Colorado strain and heterologous aMPV Minnesota strain.
Collectively, our results indicate (i) that aMPV lacking 2'-O methylation is
highly attenuated in vitro and in vivo and (ii) that inhibition of mRNA cap MTase
can serve as a novel target to rationally design live attenuated vaccines for
aMPV and perhaps other paramyxoviruses. IMPORTANCE: Paramyxoviruses include many
economically and agriculturally important viruses such as avian metapneumovirus
(aMPV), and Newcastle disease virus (NDV), human pathogens such as human
respiratory syncytial virus, human metapneumovirus, human parainfluenza virus
type 3, and measles virus, and highly lethal emerging pathogens such as Nipah
virus and Hendra virus. For many of them, there is no effective vaccine or
antiviral drug. These viruses share common strategies for viral gene expression
and replication. During transcription, paramyxoviruses produce capped,
methylated, and polyadenylated mRNAs. Using aMPV as a model, we found that viral
ribose 2'-O methyltransferase (MTase) is a novel approach to rationally attenuate
the virus for vaccine purpose. Recombinant aMPV (raMPV) lacking 2'-O MTase were
not only highly attenuated in turkeys but also provided complete protection
against the challenge of homologous and heterologous aMPV strains. This novel
approach can be applicable to other animal and human paramyxoviruses for
rationally designing live attenuated vaccines.
PMID- 25122792
TI - Kinetic and phenotypic analysis of CD8+ T cell responses after priming with
alphavirus replicons and homologous or heterologous booster immunizations.
AB - Alphavirus replicons are potent inducers of CD8(+) T cell responses and thus
constitute an attractive vaccine vector platform for developing novel vaccines.
However, the kinetics and memory phenotype of CD8(+) T cell responses induced by
alphavirus replicons are not well characterized. Furthermore, little is known how
priming with alphavirus replicons affects booster immune responses induced by
other vaccine modalities. We demonstrate here that a single immunization with an
alphavirus replicon, administered as viral particles or naked DNA, induced an
antigen-specific CD8(+) T cell response that had a sharp peak, followed by a
rapid contraction. Administering a homologous boost before contraction had
occurred did not further increase the response. In contrast, boosting after
contraction when CD8(+) T cells had obtained a memory phenotype (based on
CD127/CD62L expression), resulted in maintenance of CD8(+) T cells with a high
recall capacity (based on CD27/CD43 expression). Increasing the dose of replicon
particles promoted T effector memory (Tem) and inhibited T central memory
development. Moreover, infection with a replicating alphavirus induced a similar
distribution of CD8(+) T cells as the replicon vector. Lastly, the distribution
of T cell subpopulations induced by a DNA-launched alphavirus replicon could be
altered by heterologous boosts. For instance, boosting with a poxvirus vector
(MVA) favored expansion of the Tem compartment. In summary, we have characterized
the antigen-specific CD8(+) T cell response induced by alphavirus replicon
vectors and demonstrated how it can be altered by homologous and heterologous
boost immunizations. IMPORTANCE: Alphavirus replicons are promising vaccine
candidates against a number of diseases and are by themselves developed as
vaccines against, for example, Chikungunya virus infection. Replicons are also
considered to be used for priming, followed by booster immunization using
different vaccine modalities. In order to rationally design prime-boost
immunization schedules with these vectors, characterization of the magnitude and
phenotype of CD8(+) T cell responses induced by alphavirus replicons is needed.
Here, we demonstrate how factors such as timing and dose affect the phenotypes of
memory T cell populations induced by immunization with alphavirus replicons.
These findings are important for designing future clinical trials with
alphaviruses, since they can be used to tailor vaccination regimens in order to
induce a CD8(+) T cell response that is optimal for control and/or clearance of a
specific pathogen.
PMID- 25122794
TI - The VP4 peptide of hepatitis A virus ruptures membranes through formation of
discrete pores.
AB - Membrane-active peptides, components of capsid structural proteins, assist
viruses in overcoming the host membrane barrier in the initial stages of
infection. Several such peptides have been identified, and their roles in
membrane fusion or disruption have been characterized through biophysical
studies. In several members of the Picornaviridae family, the role of the VP4
structural peptide in cellular-membrane penetration is well established. However,
there is not much information on the membrane-penetrating capsid components of
hepatitis A virus (HAV), an unusual member of this family. The VP4 peptide of HAV
differs from its analogues in other picornaviruses in being significantly shorter
in length and in lacking a signal for myristoylation, thought to be a critical
requisite for VP4-mediated membrane penetration. Here we report, for the first
time, that the atypical VP4 in HAV contains significant membrane-penetrating
activity. Using a combination of biophysical assays and molecular dynamics
simulation studies, we show that VP4 integrates into membrane vesicles through
its N-terminal region to finally form discrete pores of 5- to 9-nm diameter,
which induces leakage in the vesicles without altering their overall size or
shape. We further demonstrate that the membrane activity of VP4 is specific
toward vesicles mimicking the lipid content of late endosomes at acidic pH. Taken
together, our data indicate that VP4 might be essential for the penetration of
host endosomal membranes and release of the viral genome during HAV entry.
IMPORTANCE: Hepatitis A virus causes acute hepatitis in humans through the fecal
oral route and is particularly prevalent in underdeveloped regions with poor
hygienic conditions. Although a vaccine for HAV exists, its high cost makes it
unsuitable for universal application in developing countries. Studies on host
virus interaction for HAV have been hampered due to a lack of starting material,
since the virus is extremely slow growing in culture. Among the unknown aspects
of the HAV life cycle is its manner of host membrane penetration, which is one of
the most important initial steps in viral infection. Here, we present data to
suggest that a small peptide, VP4, a component of the HAV structural polyprotein,
might be essential in helping the viral genome cross cell membranes during entry.
It is hoped that this work might help in elucidating the manner of initial host
cell interaction by HAV.
PMID- 25122793
TI - Apolipoprotein E likely contributes to a maturation step of infectious hepatitis
C virus particles and interacts with viral envelope glycoproteins.
AB - The assembly of infectious hepatitis C virus (HCV) particles is tightly linked to
components of the very-low-density lipoprotein (VLDL) pathway. We and others have
shown that apolipoprotein E (ApoE) plays a major role in production of infectious
HCV particles. However, the mechanism by which ApoE contributes to virion
assembly/release and how it gets associated with the HCV particle is poorly
understood. We found that knockdown of ApoE reduces titers of infectious intra-
and extracellular HCV but not of the related dengue virus. ApoE depletion also
reduced amounts of extracellular HCV core protein without affecting intracellular
core amounts. Moreover, we found that ApoE depletion affected neither formation
of nucleocapsids nor their envelopment, suggesting that ApoE acts at a late step
of assembly, such as particle maturation and infectivity. Importantly, we
demonstrate that ApoE interacts with the HCV envelope glycoproteins, most notably
E2. This interaction did not require any other viral proteins and depended on the
transmembrane domain of E2 that also was required for recruitment of HCV envelope
glycoproteins to detergent-resistant membrane fractions. These results suggest
that ApoE plays an important role in HCV particle maturation, presumably by
direct interaction with viral envelope glycoproteins. IMPORTANCE: The HCV
replication cycle is tightly linked to host cell lipid pathways and components.
This is best illustrated by the dependency of HCV assembly on lipid droplets and
the VLDL component ApoE. Although the role of ApoE for production of infectious
HCV particles is well established, it is still poorly understood how ApoE
contributes to virion formation and how it gets associated with HCV particles.
Here, we provide experimental evidence that ApoE likely is required for an
intracellular maturation step of HCV particles. Moreover, we demonstrate that
ApoE associates with the viral envelope glycoproteins. This interaction appears
to be dispensable for envelopment of virus particles but likely contributes to
the quality control of secreted infectious virions. These results shed new light
on the exploitation of host cell lipid pathways by HCV and the link of viral
particle assembly to the VLDL component ApoE.
PMID- 25122795
TI - Inhibition of breast cancer cell proliferation through disturbance of the
calcineurin/NFAT pathway by human herpesvirus 6B U54 tegument protein.
AB - Nuclear factor of activated T cell (NFAT) proteins are key regulators involved in
multiple physiological mechanisms, such as immune response and cell growth. The
capacity of selective calcineurin/NFAT inhibitors to decrease NFAT-dependent
cancer cell progression, particularly in breast cancer, has already been
demonstrated. In this study, we report a role for the human herpesvirus 6B (HHV
6B) U54 tegument protein in inhibiting MCF-7 breast cancer cell proliferation by
inhibiting NFAT activation.
PMID- 25122796
TI - High frequencies of polyfunctional CD8+ NK cells in chronic HIV-1 infection are
associated with slower disease progression.
AB - Natural killer (NK) cells are effector and regulatory innate immune cells and
play a critical role in the first line of defense against various viral
infections. Although previous reports have indicated the vital contributions of
NK cells to HIV-1 immune control, nongenetic NK cell parameters directly
associated with slower disease progression have not been defined yet. In a
longitudinal, retrospective study of 117 untreated HIV-infected subjects, we show
that higher frequencies as well as the absolute numbers of CD8(+) CD3(-)
lymphocytes are linked to delayed HIV-1 disease progression. We show that the
majority of these cells are well-described blood NK cells. In a subsequent cross
sectional study, we demonstrate a significant loss of CD8(+) NK cells in
untreated HIV-infected individuals, which correlated with HIV loads and inversely
correlated with CD4(+) T cell counts. CD8(+) NK cells had modestly higher
frequencies of CD57-expressing cells than CD8(-) cells, but CD8(+) and CD8(-) NK
cells showed no differences in the expression of a number of activating and
inhibiting NK cell receptors. However, CD8(+) NK cells exhibited a more
functional profile, as detected by cytokine production and degranulation.
IMPORTANCE: We demonstrate that the frequency of highly functional CD8(+) NK
cells is inversely associated with HIV-related disease markers and linked with
delayed disease progression. These results thus indicate that CD8(+) NK cells
represent a novel NK cell-derived, innate immune correlate with an improved
clinical outcome in HIV infection.
PMID- 25122797
TI - Inhibition of interleukin-2 gene expression by human herpesvirus 6B U54 tegument
protein.
AB - Human herpesvirus 6B (HHV-6B) is a ubiquitous pathogen causing lifelong
infections in approximately 95% of humans worldwide. To persist within its host,
HHV-6B has developed several immune evasion mechanisms, such as latency, during
which minimal proteins are expressed, and the ability to disturb innate and
adaptive immune responses. The primary cellular targets of HHV-6B are CD4(+) T
cells. Previous studies by Flamand et al. (L. Flamand, J. Gosselin, I.
Stefanescu, D. Ablashi, and J. Menezes, Blood 85:1263-1271, 1995) reported on the
capacity of HHV-6A as well as UV-irradiated HHV-6A to inhibit interleukin-2 (IL
2) synthesis in CD4(+) lymphocytes, suggesting that viral structural components
could be responsible for this effect. In the present study, we identified the HHV
6B U54 tegument protein (U54) as being capable of inhibiting IL-2 expression. U54
binds the calcineurin (CaN) phosphatase enzyme, causing improper
dephosphorylation and nuclear translocation of NFAT (nuclear factor of activated
T cells) proteins, resulting in suboptimal IL-2 gene transcription. The U54 GISIT
motif (amino acids 293 to 297), analogous to the NFAT PXIXIT motif, contributed
to the inhibition of NFAT activation. IMPORTANCE Human herpesvirus 6A (HHV-6A)
and HHV-6B are associated with an increasing number of pathologies. These viruses
have developed strategies to avoid the immune response allowing them to persist
in the host. Several studies have illustrated mechanisms by which HHV-6A and HHV
6B are able to disrupt host defenses (reviewed in L. Dagna, J. C. Pritchett, and
P. Lusso, Future Virol. 8:273-287, 2013, doi:10.2217/fvl.13.7). Previous work
informed us that HHV-6A is able to suppress synthesis of interleukin-2 (IL-2), a
key immune growth factor essential for adequate T lymphocyte proliferation and
expansion. We obtained evidence that HHV-6B also inhibits IL-2 gene expression
and identified the mechanisms by which it does so. Our work led us to the
identification of U54, a virion-associated tegument protein, as being responsible
for suppression of IL-2. Consequently, we have identified HHV-6B U54 protein as
playing a role in immune evasion. These results further contribute to our
understanding of HHV-6 interactions with its human host and the efforts deployed
to ensure its long-term persistence.
PMID- 25122798
TI - Polyomavirus small T antigen interacts with yes-associated protein to regulate
cell survival and differentiation.
AB - Murine polyomavirus small t antigen (PyST) regulates cell cycle, cell survival,
apoptosis, and differentiation and cooperates with middle T antigen (MT) to
transform primary cells in vitro and in vivo. Like all polyomavirus T antigens,
PyST functions largely via its interactions with host cell proteins. Here, we
show that PyST binds both Yes-associated protein 1 (YAP1) and YAP2, integral
parts of the Hippo signaling pathway, which is a subject of increasing interest
in human cancer. The transcription factor TEAD, which is a known target of YAP,
is also found in PyST complexes. PyST enhanced YAP association with protein
phosphatase 2A (PP2A), leading to decreased YAP phosphorylation. PyST increased
YAP levels by decreasing its degradation. This effect was mediated by a reduction
in YAP association with beta-transducin repeat protein (betaTRCP), which is known
to regulate YAP turnover in a phosphorylation-dependent manner. Genetic analysis
has identified PyST mutants defective in YAP binding. These mutants demonstrated
that YAP binding is important for PyST to block myoblast differentiation and to
synergize with the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) to
promote cell death in 3T3-L1 preadipocytes placed under differentiation
conditions. In addition to YAP binding, both of these phenotypes require PyST
binding to PP2A. Importance: The Hippo/YAP pathway is a highly conserved cascade
important for tissue development and homeostasis. Defects in this pathway are
increasingly being associated with cancer. Polyomavirus small t antigen is a
viral oncogene that cooperates with middle T antigen in transformation. On its
own, small t antigen controls cell survival and differentiation. By binding YAP,
small t antigen brings it together with protein phosphatase 2A. This work shows
how this association of small t antigen with YAP is important for its effects on
cell phenotype. It also suggests that PyST can be used to characterize cellular
processes that are regulated by YAP.
PMID- 25122799
TI - The composition of West Nile virus lipid envelope unveils a role of sphingolipid
metabolism in flavivirus biogenesis.
AB - West Nile virus (WNV) is an emerging zoonotic mosquito-borne flavivirus
responsible for outbreaks of febrile illness and meningoencephalitis. The
replication of WNV takes place on virus-modified membranes from the endoplasmic
reticulum of the host cell, and virions acquire their envelope by budding into
this organelle. Consistent with this view, the cellular biology of this pathogen
is intimately linked to modifications of the intracellular membranes, and the
requirement for specific lipids, such as cholesterol and fatty acids, has been
documented. In this study, we evaluated the impact of WNV infection on two
important components of cellular membranes, glycerophospholipids and
sphingolipids, by mass spectrometry of infected cells. A significant increase in
the content of several glycerophospholipids (phosphatidylcholine, plasmalogens,
and lysophospholipids) and sphingolipids (ceramide, dihydroceramide, and
sphingomyelin) was noticed in WNV-infected cells, suggesting that these lipids
have functional roles during WNV infection. Furthermore, the analysis of the
lipid envelope of WNV virions and recombinant virus-like particles revealed that
their envelopes had a unique composition. The envelopes were enriched in
sphingolipids (sphingomyelin) and showed reduced levels of phosphatidylcholine,
similar to sphingolipid-enriched lipid microdomains. Inhibition of neutral
sphingomyelinase (which catalyzes the hydrolysis of sphingomyelin into ceramide)
by either pharmacological approaches or small interfering RNA-mediated silencing
reduced the release of flavivirus virions as well as virus-like particles,
suggesting a role of sphingomyelin-to-ceramide conversion in flavivirus budding
and confirming the importance of sphingolipids in the biogenesis of WNV.
Importance: West Nile virus (WNV) is a neurotropic flavivirus spread by
mosquitoes that can infect multiple vertebrate hosts, including humans. There is
no specific vaccine or therapy against this pathogen licensed for human use.
Since the multiplication of this virus is associated with rearrangements of host
cell membranes, we analyzed the effect of WNV infection on different cellular
lipids that constitute important membrane components. The levels of multiple
lipid species were increased in infected cells, pointing to the induction of
major alterations of cellular lipid metabolism by WNV infection. Interestingly,
certain sphingolipids, which were increased in infected cells, were also enriched
in the lipid envelope of the virus, thus suggesting a potential role during virus
assembly. We further verified the role of sphingolipids in the production of WNV
by means of functional analyses. This study provides new insight into the
formation of flavivirus infectious particles and the involvement of sphingolipids
in the WNV life cycle.
PMID- 25122800
TI - Regulation of autophagic activation by Rta of Epstein-Barr virus via the
extracellular signal-regulated kinase pathway.
AB - Autophagy is an intracellular degradation pathway that provides a host defense
mechanism against intracellular pathogens. However, many viruses exploit this
mechanism to promote their replication. This study shows that lytic induction of
Epstein-Barr virus (EBV) increases the membrane-bound form of LC3 (LC3-II) and
LC3-containing punctate structures in EBV-positive cells. Transfecting 293T cells
with a plasmid that expresses Rta also induces autophagy, revealing that Rta is
responsible for autophagic activation. The activation involves Atg5, a key
component of autophagy, but not the mTOR pathway. The expression of Rta also
activates the transcription of the genes that participate in the formation of
autophagosomes, including LC3A, LC3B, and ATG9B genes, as well as those that are
involved in the regulation of autophagy, including the genes TNF, IRGM, and
TRAIL. Additionally, treatment with U0126 inhibits the Rta-induced autophagy and
the expression of autophagy genes, indicating that the autophagic activation is
caused by the activation of extracellular signal-regulated kinase (ERK) signaling
by Rta. Finally, the inhibition of autophagic activity by an autophagy inhibitor,
3-methyladenine, or Atg5 small interfering RNA, reduces the expression of EBV
lytic proteins and the production of viral particles, revealing that autophagy is
critical to EBV lytic progression. This investigation reveals how an EBV-encoded
transcription factor promotes autophagy to affect viral lytic development.
PMID- 25122801
TI - Combined alphavirus replicon particle vaccine induces durable and cross
protective immune responses against equine encephalitis viruses.
AB - Alphavirus replicons were evaluated as potential vaccine candidates for
Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus
(WEEV), or eastern equine encephalitis virus (EEEV) when given individually or in
combination (V/W/E) to mice or cynomolgus macaques. Individual replicon vaccines
or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies
in mice to their respective alphavirus. Protection from either subcutaneous or
aerosol challenge with VEEV, WEEV, or EEEV was demonstrated out to 12 months
after vaccination in mice. Individual replicon vaccines or the combination V/W/E
replicon vaccine elicited strong neutralizing antibodies in macaques and
demonstrated good protection against aerosol challenge with an epizootic VEEV-IAB
virus, Trinidad donkey. Similarly, the EEEV replicon and V/W/E combination
vaccine elicited neutralizing antibodies against EEEV and protected against
aerosol exposure to a North American variety of EEEV. Both the WEEV replicon and
combination V/W/E vaccination, however, elicited poor neutralizing antibodies to
WEEV in macaques, and the protection conferred was not as strong. These results
demonstrate that a combination V/W/E vaccine is possible for protection against
aerosol challenge and that cross-interference between the vaccines is minimal.
Importance: Three related viruses belonging to the genus Alphavirus cause severe
encephalitis in humans: Venezuelan equine encephalitis virus (VEEV), western
equine encephalitis virus (WEEV), and eastern equine encephalitis virus (EEEV).
Normally transmitted by mosquitoes, these viruses can cause disease when inhaled,
so there is concern that these viruses could be used as biological weapons. Prior
reports have suggested that vaccines for these three viruses might interfere with
one another. We have developed a combined vaccine for Venezuelan equine
encephalitis, western equine encephalitis, and eastern equine encephalitis
expressing the surface proteins of all three viruses. In this report we
demonstrate in both mice and macaques that this combined vaccine is safe,
generates a strong immune response, and protects against aerosol challenge with
the viruses that cause Venezuelan equine encephalitis, western equine
encephalitis, and eastern equine encephalitis.
PMID- 25122804
TI - My second-favourite medical journal.
PMID- 25122802
TI - DESC1 and MSPL activate influenza A viruses and emerging coronaviruses for host
cell entry.
AB - The type II transmembrane serine protease (TTSP) TMPRSS2 cleaves and activates
the influenza virus and coronavirus surface proteins. Expression of TMPRSS2 is
essential for the spread and pathogenesis of H1N1 influenza viruses in mice. In
contrast, H3N2 viruses are less dependent on TMPRSS2 for viral amplification,
suggesting that these viruses might employ other TTSPs for their activation.
Here, we analyzed TTSPs, reported to be expressed in the respiratory system, for
the ability to activate influenza viruses and coronaviruses. We found that MSPL
and, to a lesser degree, DESC1 are expressed in human lung tissue and cleave and
activate the spike proteins of the Middle East respiratory syndrome and severe
acute respiratory syndrome coronaviruses for cell-cell and virus-cell fusion. In
addition, we show that these proteases support the spread of all influenza virus
subtypes previously pandemic in humans. In sum, we identified two host cell
proteases that could promote the amplification of influenza viruses and emerging
coronaviruses in humans and might constitute targets for antiviral intervention.
Importance: Activation of influenza viruses by host cell proteases is essential
for viral infectivity and the enzymes responsible are potential targets for
antiviral intervention. The present study demonstrates that two cellular serine
proteases, DESC1 and MSPL, activate influenza viruses and emerging coronaviruses
in cell culture and, because of their expression in human lung tissue, might
promote viral spread in the infected host. Antiviral strategies aiming to prevent
viral activation might thus need to encompass inhibitors targeting MSPL and
DESC1.
PMID- 25122806
TI - Industry involvement in continuing medical education: time to say no.
PMID- 25122807
TI - Realigning training with need: A case for mandatory family medicine resident
experience in community-based care of the frail elderly.
PMID- 25122810
TI - Logic of care.
PMID- 25122803
TI - Counteracting effects of cellular Notch and Epstein-Barr virus EBNA2:
implications for stromal effects on virus-host interactions.
AB - A number of diverse environmental cues have been linked to B lymphocyte
differentiation and activation. One such cue, Notch-2, may be particularly
relevant to the biology of infection with Epstein-Barr virus (EBV), which
colonizes the B cell compartment. Activated Notch and EBV nuclear antigen 2
(EBNA2) both function as transcriptional activators by virtue of their
interactions with the transcription factor RBP-Jkappa. Although EBNA2 and
activated Notch appear to have partially overlapping functions, we now report
that activated Notch counteracts a crucial EBNA2 function both in newly infected
primary B cells and in lymphoblastoid cell lines (LCLs). EBNA2 is directly
responsible for the initiation of transcription of the majority of EBV proteins
associated with type III latency, leading to the outgrowth of LCLs. One of the
key proteins driving this outgrowth is latent membrane protein 1 (LMP1), which is
regulated by an EBNA2-responsive element within its ED-L1 promoter. Activation of
Notch-2 via Delta-like ligand 1 inhibits EBNA2-mediated initiation of LMP1
transcription. Furthermore, ligated Notch-2 also efficiently turns off LMP1
expression from the ED-L1 promoter in LCLs already expressing LMP1. Modulation of
EBV gene expression by Notch was not confined to EBNA2-dependent events.
Activated Notch-2 also inhibited EBV entry into the lytic cycle in a B cell non
Hodgkin's lymphoma line by upregulating the cellular transcription factor Zeb2,
which represses the transcription of BZLF1. These results support the concept
that in vivo, cumulative signals from the microenvironment downregulate EBV gene
expression in B cells to the latency 0 gene expression profile observed in B
cells entering the peripheral blood. Importance: Experimental infection of
resting B cells by Epstein-Barr virus leads to the growth transformation program
of virus gene expression and the outgrowth of lymphoblastoid cell lines. Previous
studies at the single-cell level revealed complex cellular and viral signaling
networks regulating transcription of the viral genome. This study demonstrates
that viral gene expression can also be radically altered by molecules expressed
on stromal cells in the microenvironment of lymphoid tissue, specifically, Delta
like ligand 1 on stromal cells ligating Notch-2 on infected B cells. Activation
of Notch interferes with the transactivation function of EBNA2, downregulates the
expression of LMP1 and LMP2a, and inhibits the activation of lytic virus
replication in a B cell non-Hodgkin's lymphoma line by preventing expression of
BZLF1. The significance of these observations is that they indicate new
mechanisms whereby the microenvironment in normal lymphoid tissue may facilitate
the repression of viral gene expression, enabling establishment of true latency
in memory B cells.
PMID- 25122811
TI - Clinical review or hypothesis?
PMID- 25122812
TI - Response.
PMID- 25122814
TI - Guideline for referral of patients with suspected lung cancer by family
physicians and other primary care providers.
AB - OBJECTIVE: The aim of this guideline is to assist FPs and other primary care
providers with recognizing features that should raise their suspicions about the
presence of lung cancer in their patients. COMPOSITION OF THE COMMITTEE:
Committee members were selected from among the regional primary care leads from
the Cancer Care Ontario Provincial Primary Care and Cancer Network and from among
the members of the Cancer Care Ontario Lung Cancer Disease Site Group. METHODS:
This guideline was developed through systematic review of the evidence base,
synthesis of the evidence, and formal external review involving Canadian
stakeholders to validate the relevance of recommendations. REPORT: Evidence-based
guidelines were developed to improve the management of patients presenting with
clinical features of lung cancer within the Canadian context. CONCLUSION: Earlier
identification and referral of patients with lung cancer might ultimately help
improve lung cancer morbidity and mortality. These guidelines might also be of
value for informing the development of lung cancer diagnostic programs and for
helping policy makers to ensure appropriate resources are in place.
PMID- 25122815
TI - Guideline for referral of patients with suspected colorectal cancer by family
physicians and other primary care providers.
AB - OBJECTIVE: The aim of this guideline is to assist FPs and other primary care
providers with recognizing features that should raise their suspicions about the
presence of colorectal cancer (CRC) in their patients. COMPOSITION OF THE
COMMITTEE: Committee members were selected from among the regional primary care
leads from the Cancer Care Ontario Provincial Primary Care and Cancer Network,
the members of the Ontario Colorectal Cancer Screening Advisory Committee, and
the members of the Cancer Care Ontario Gastrointestinal Cancer Disease Site
Group. METHODS: This guideline was developed through systematic review of the
evidence base, synthesis of the evidence, and formal external review involving
Canadian stakeholders to validate the relevance of recommendations. REPORT:
Evidence-based guidelines were developed to improve the management of patients
presenting with clinical features of CRC within the Canadian context. CONCLUSION:
The judicious balancing of suspicion of CRC and level of risk of CRC should
encourage timely referral by FPs and primary care providers. This guideline might
also inform indications for referral to CRC diagnostic assessment programs.
PMID- 25122818
TI - Practical strategies for prevention and treatment of heat-induced illness.
PMID- 25122816
TI - Consuming non-alcoholic beer and other beverages during pregnancy and
breastfeeding.
AB - QUESTION: An increasing number of my patients are asking about the safety of
consuming non-alcoholic beer and other alcohol-free versions of alcoholic
beverages during pregnancy and breastfeeding, as they believe that these drinks
might be a "safer" alternative to regular alcoholic beverages. What are
Motherisk's recommendations regarding these products? ANSWER: Such drinks might
contain higher ethanol levels than what is indicated on their labels. As there is
no known safe level of alcohol intake in pregnancy, abstinence from non-alcoholic
beverages would eliminate any risk of fetal alcohol spectrum disorder. Although
it is likely that moderate intake of non-alcoholic beverages would pose no harm
to breastfed infants, briefly delaying breastfeeding after consumption of such
drinks would ensure that the infant is not exposed to alcohol.
PMID- 25122817
TI - Accidental digital epinephrine injection: to treat or not to treat?
PMID- 25122820
TI - A horse-and-buggy kind of doctor.
PMID- 25122821
TI - Dr Agnes Kluz MD CCFP.
PMID- 25122822
TI - Balancing life and work.
PMID- 25122819
TI - Colorectal cancer risk information presented by a nonphysician assistant does not
increase screening rates.
AB - OBJECTIVE: To determine the effectiveness of presenting individualized colorectal
cancer (CRC) risk information for increasing CRC screening rates in primary care
patients at above-average risk of CRC. DESIGN: Randomized controlled trial.
SETTING: Georgia Regents University in Augusta-an academic family medicine clinic
in the southeastern United States. PARTICIPANTS: Outpatients (50 to 70 years of
age) scheduled for routine visits in the family medicine clinic who were
determined to be at above-average risk of CRC. INTERVENTIONS: Individualized CRC
risk information calculated from the Your Disease Risk tool compared with a
standard CRC screening handout. MAIN OUTCOME MEASURES: Intention to complete CRC
screening. Secondary measures included the proportions of subjects completing
fecal occult blood tests, flexible sigmoidoscopy, and colonoscopy. RESULTS: A
total of 1147 consecutive records were reviewed to determine eligibility.
Overall, 210 (37.7%) of 557 eligible participants were randomized to receive
either individualized CRC risk information (prepared by a research assistant) or
a standard CRC screening handout. The intervention group had a mean (SD) age of
55.7 (4.8) years and the control group had a mean (SD) age of 55.6 (4.6) years.
Two-thirds of the participants in each group were female. The intervention group
and the control group were matched by race (P = .40). There was no significant
difference between groups for intention to complete CRC screening (P = .58).
Overall, 26.7% of the intervention participants and 27.7% of the control
participants completed 1 or more CRC screening tests (P = .66). CONCLUSION:
Presentation of individualized CRC risk information by a nonphysician assistant
as a decision aid did not result in higher CRC screening rates in primary care
patients compared with presentation of general CRC screening information. Future
research is needed to determine if physician presentation of CRC risk information
would result in increased screening rates compared with research assistant
presentation.
PMID- 25122825
TI - Meet Dr Pamela Eisener-Parsche: Our new Associate Executive Director and Director
of Academic Family Medicine.
PMID- 25122828
TI - Statins and cognitive impairment.
PMID- 25122830
TI - Systematic review of guidelines for the management of suspected lung cancer in
primary care.
AB - OBJECTIVE: To systematically review the literature and provide an update and
integration of existing peer-reviewed guidelines with recent systematic reviews
and with primary studies related to the early recognition and management of lung
cancer in primary care. DATA SOURCES: MEDLINE and EMBASE were searched for
relevant articles. The quality of the evidence to support existing guideline
recommendations, and the consistency of recommendations with updated evidence,
were assessed. Applicability in a Canadian primary care setting was also
evaluated. STUDY SELECTION: All studies that explored signs or symptoms of or
risk factors for lung cancer in the primary care setting were included. All
diagnostic studies in which symptomatic primary care patients underwent 1 or more
investigations were also searched. SYNTHESIS: Recommendations were consistent
among guidelines despite a paucity of supporting evidence. Updated evidence
provided further support for the recommendations. Recommendations for identifying
signs and symptoms of lung cancer presenting in primary care and for initial
management can be adopted and applied within a Canadian primary care setting.
CONCLUSION: This updated review of recommendations might help promote evidence
based practice and, ultimately, more timely management and improved prognosis for
lung cancer patients. It might also assist in the development of lung cancer
diagnostic assessment programs.
PMID- 25122831
TI - Systematic review of clinical features of suspected colorectal cancer in primary
care.
AB - OBJECTIVE: To systematically review the diagnostic accuracy of clinical features
associated with colorectal cancer (CRC) presenting in primary care. DATA SOURCES:
MEDLINE and EMBASE were searched for studies in primary care that provided
information on clinical features predictive of CRC. Positive predictive values
were used to guide the determination of clinical features associated with
increased risk of CRC. STUDY SELECTION: Systematic reviews or primary studies
that provided possible clinical features predictive of CRC were included.
SYNTHESIS: Clinical features of patients presenting in primary care that are
associated with increased risk of CRC, listed in descending order of association,
included palpable rectal or abdominal mass; rectal bleeding combined with weight
loss; iron deficiency anemia; rectal bleeding mixed with stool; rectal bleeding
in the absence of perianal symptoms; rectal bleeding combined with change in
bowel habits; dark rectal bleeding; rectal bleeding and diarrhea; and change in
bowel habits. Being male and increasing age were also, in general, associated
with increased risk of CRC. CONCLUSION: Recognition of clinical features
associated with increased risk of CRC by FPs might help with earlier
identification and referral among patients presenting in primary care. This
review might help inform providers and CRC diagnostic assessment programs about
indications for assessment and further investigation.
PMID- 25122832
TI - Collaboration between family physicians and nurse clinicians: opinions of
graduates in family medicine.
AB - OBJECTIVE: To determine whether graduating family physicians are exposed to
collaboration between family physicians and nurse clinicians during their
training, as well as their opinions about shared care between doctors and nurse
clinicians in the delivery of patient care. DESIGN: Anonymous online survey.
SETTING: Two French-Canadian university family medicine residency programs.
PARTICIPANTS: The 2010 and 2011 graduating family physicians (N = 343) from the
University of Montreal and Laval University in Quebec. MAIN OUTCOME MEASURES: The
extent to which nurse clinicians in graduating family physicians' training milieu
were involved in preventive and curative patient care activities, and graduates'
opinions about nurse clinicians sharing care with physicians. RESULTS: Of 343
graduates, 186 (54.2%) participated in the survey. Although as residents in
family medicine their exposure to shared care with nurse clinicians was somewhat
limited, respondents indicated that they were generally quite open to the idea of
sharing care with nurse clinicians. More than 70% of respondents agreed or
strongly agreed that nurse clinicians could adjust, according to protocols of
clinical guidelines, the treatment of patients with diabetes, hypertension, and
asthma, as well as regulate medication for pain control in terminally ill
patients. By contrast, respondents were less favourable to nurse clinicians
adjusting the treatment of patients with depression. More than 80% of respondents
agreed or strongly agreed that nurse clinicians could initiate treatment via a
medical directive for routine hormonal contraception, acne, uncomplicated
cystitis, and sexually transmitted infections. Respondents' opinions on nurse
clinicians initiating treatment for pharyngitis and otitis were more divided.
CONCLUSION: Graduating family physicians are quite open to collaborating with
nurse clinicians. Although they have observed some collaboration between
physicians and nurses, there are areas of shared clinical activities in which
they would benefit from further exposure and training.
PMID- 25122833
TI - Simultaneous quantification of furanocoumarins from Aegle marmelos fruit pulp
extract.
AB - Aegle marmelos Correa (Rutaceae) is a prominent species in the Sub-Himalayan
region, also found in central and south India, and has been widely used as remedy
for diarrhea and dysentery. Unripe fruits show antiviral activity and prove to be
a potent hypoglycemic agent. In this study, a high-performance liquid
chromatography (HPLC) method for the simultaneous quantification of major
furocoumarin components marmelosin, psoralen and bergapten in the extract from
fruit pulp of A. marmelos has been developed. Components were found in the range
of 5-6.5, >0.4-0.75 and >0.25 mg/g of dried fruit weight, respectively. The
method was validated for linearity, precision, accuracy, robustness, limit of
detection and limit of quantification. Linearity was determined over the range of
5-40 ug/mL (r > 0.965). Intra- and interday precision showed a relative standard
deviation of <2.5%. The accuracy of the method was determined by a spike recovery
study, and the average recoveries were 99.46, 101.04 and 100.8% for marmelosin,
psoralen and bergapten, respectively. The proposed HPLC method was found to be
simple, precise and specific and can be used simultaneously for the routine
quality control of raw materials of A. marmelos fruit extracts and their
products, and also other products containing these markers.
PMID- 25122834
TI - Simultaneously optimizing spatial spectral features based on mutual information
for EEG classification.
AB - High performance of the brain-computer interface (BCI) needs efficient algorithms
to extract discriminative features from raw electroencephalography (EEG) signals.
In this paper, we present a novel scheme to extract spatial spectral features for
the motor imagery-based BCI. The learning task is formulated by maximizing the
mutual information between spatial spectral features (MMISS) and class labels, by
which a unique objective function directly related to Bayes classification error
is optimized. The spatial spectral features are assumed to follow a parametric
Gaussian distribution, which has been validated by the normal distribution
Mardia's test, and under this assumption the estimation of mutual information is
derived. We propose a gradient based alternative and iterative learning algorithm
to optimize the cost function and derive the spatial and spectral filters
simultaneously. The experimental results on dataset IVa of BCI competition III
and dataset IIa of BCI competition IV show that the proposed MMISS is able to
efficiently extract discriminative features from motor imagery-based EEG signals
to enhance the classification accuracy compared to other existing algorithms.
PMID- 25122835
TI - Hierarchical String Cuts: A Translation, Rotation, Scale and Mirror Invariant
Descriptor for Fast Shape Retrieval.
AB - This paper presents a novel approach for both fast and accurately retrieving
similar shapes. A hierarchical string cuts (HSC) method is proposed to partition
a shape into multiple level curve segments of different lengths from a point
moving around the contour to describe the shape gradually and completely from the
global information to the finest details. At each hierarchical level, the curve
segments are cut by strings to extract features that characterize the geometric
and distribution properties in that particular level of details. The translation,
rotation, scale and mirror invariant HSC descriptor enables a fast metric based
matching to achieve the desired high accuracy. Encouraging experimental results
on four databases demonstrated that the proposed method can consistently achieve
higher (or similar) retrieval accuracies than the state-of-the-art benchmarks
with a more than 120 times faster speed. This may suggest a new way of developing
shape retrieval techniques in which a high accuracy can be achieved by a fast
metric matching algorithm without using the time-consuming correspondence
optimisation strategy.
PMID- 25122837
TI - The lightweight Delft Cylinder Hand: first multi-articulating hand that meets the
basic user requirements.
AB - Rejection rates of upper limb prostheses are high (23%-45%). Amputees indicate
that the highest design priority should be reduction of the mass of the
prosthetic device. Despite all efforts, the mass of the new prosthetic hands is
35%-73% higher than that of older hands. Furthermore, current hands are thicker
than a human hand, they operate slower and do not provide proprioceptive force
and position feedback. This study presents the Delft Cylinder Hand, a body
powered prosthetic hand which mass is 55%-68% lower than that of the lightest
current prosthetic hands, operates faster, has an anthropomorphic shape, and
provides proprioceptive force and position feedback. The hand has articulating
fingers, actuated by miniature hydraulic cylinders. The articulating fingers
adapt to the shape of the grasped object. Its functional scores are similar to
that of current prosthetic devices. The hand has a higher mechanical performance
than current body-powered hands. It requires 49%-162% less energy from the user
and it can deliver a higher maximum pinch force (30-60 N).
PMID- 25122836
TI - Hierarchy of neural organization in the embryonic spinal cord: Granger-causality
graph analysis of in vivo calcium imaging data.
AB - The recent development of genetically encoded calcium indicators enables
monitoring in vivo the activity of neuronal populations. Most analysis of these
calcium transients relies on linear regression analysis based on the sensory
stimulus applied or the behavior observed. To estimate the basic properties of
the functional neural circuitry, we propose a network approach to calcium imaging
recorded at single cell resolution. Differently from previous analysis based on
cross-correlation, we used Granger-causality estimates to infer information
propagation between the activities of different neurons. The resulting functional
network was then modeled as a directed graph and characterized in terms of
connectivity and node centralities. We applied our approach to calcium transients
recorded at low frequency (4 Hz) in ventral neurons of the zebrafish spinal cord
at the embryonic stage when spontaneous coiling of the tail occurs. Our analysis
on population calcium imaging data revealed a strong ipsilateral connectivity and
a characteristic hierarchical organization of the network hubs that supported
established propagation of activity from rostral to caudal spinal cord. Our
method could be used for detecting functional defects in neuronal circuitry
during development and pathological conditions.
PMID- 25122838
TI - Theoretical modeling and experimental validation of surface stress in thrombin
aptasensor.
AB - Adsorption of target molecules on the immobilized microcantilever surface
produced beam displacement due to the differential surface stress generated
between the immobilized and non-immobilized surface. Surface stress is caused by
the intermolecular forces between the molecules. Van der Waals, electrostatic
forces, hydrogen bonding, hydrophobic effect and steric hindrance are some of the
intermolecular forces involved. A theoretical framework describing the adsorption
induced microcantilever displacement is derived in this paper. Experimental
displacement of thrombin aptamer-thrombin interactions was carried out. The
relation between the electrostatic interactions involved between adsorbates
(thrombin) as well as adsorbates and substrates (thrombin aptamer) and the
microcantilever beam displacement utilizing the proposed mathematical model was
quantified and compared to the experimental value. This exercise is important to
aid the designers in microcantilever sensing performance optimization.
PMID- 25122839
TI - Measurement of intravenously administered gamma-Fe2O3 particle amount in mice
tissues using vibrating sample magnetometer.
AB - Dispersions of platelet gamma-Fe2O3 particles 30-50nm in size were intravenously
administered to mice and the amount of particles accumulated in each tissue was
obtained by magnetization measurement using a vibrating sample magnetometer.
Background noise was greatly reduced by measuring dried tissues under a magnetic
field of 500 Oe so that the effect of diamagnetism was slight. Remarkable
particle accumulation was observed in the liver and spleen. Considerable particle
accumulation was observed in the lung when a large quantity of gamma-Fe2 O3
particles was administered. There was no significant particle accumulation in the
kidney and heart.
PMID- 25122840
TI - Prediction of essential proteins based on overlapping essential modules.
AB - Many computational methods have been proposed to identify essential proteins by
using the topological features of interactome networks. However, the precision of
essential protein discovery still needs to be improved. Researches show that
majority of hubs (essential proteins) in the yeast interactome network are
essential due to their involvement in essential complex biological modules and
hubs can be classified into two categories: date hubs and party hubs. In this
study, combining with gene expression profiles, we propose a new method to
predict essential proteins based on overlapping essential modules, named POEM. In
POEM, the original protein interactome network is partitioned into many
overlapping essential modules. The frequencies and weighted degrees of proteins
in these modules are employed to decide which categories does a protein belong
to? The comparative results show that POEM outperforms the classical centrality
measures: Degree Centrality (DC), Information Centrality (IC), Eigenvector
Centrality (EC), Subgraph Centrality (SC), Betweenness Centrality (BC), Closeness
Centrality (CC), Edge Clustering Coefficient Centrality (NC), and two newly
proposed essential proteins prediction methods: PeC and CoEWC. Experimental
results indicate that the precision of predicting essential proteins can be
improved by considering the modularity of proteins and integrating gene
expression profiles with network topological features.
PMID- 25122841
TI - Biological analysis of Jeffrey nanofluid in a curved channel with heat
dissipation.
AB - This study examines the peristaltic flow of Jeffrey nanofluid in a curved
channel. The governing equations of Jeffrey nanofluid model for curved channel
are derived including the effects of curvature. The highly nonlinear partial
differential equations are simplified by using the long wave length and low
Reynolds number assumptions. The reduced nonlinear partial differential equations
are solved analytically with the help of homotopy perturbation method. The
expression for pressure rise is computed through numerical integration. The
physical features of pertinent parameters have been discussed by plotting the
graphs of pressure rise, velocity, temperature, nanoparticle volume fraction and
stream functions. It is observed that the curve-ness of the channel decreases the
pressure rise in the peristaltic pumping region. Moreover, curve-ness of the
channel effects the fluid flow by decreasing the fluid velocity near inner wall
and increasing the velocity near the outer wall of the channel.
PMID- 25122842
TI - Blind image quality assessment via deep learning.
AB - This paper investigates how to blindly evaluate the visual quality of an image by
learning rules from linguistic descriptions. Extensive psychological evidence
shows that humans prefer to conduct evaluations qualitatively rather than
numerically. The qualitative evaluations are then converted into the numerical
scores to fairly benchmark objective image quality assessment (IQA) metrics.
Recently, lots of learning-based IQA models are proposed by analyzing the mapping
from the images to numerical ratings. However, the learnt mapping can hardly be
accurate enough because some information has been lost in such an irreversible
conversion from the linguistic descriptions to numerical scores. In this paper,
we propose a blind IQA model, which learns qualitative evaluations directly and
outputs numerical scores for general utilization and fair comparison. Images are
represented by natural scene statistics features. A discriminative deep model is
trained to classify the features into five grades, corresponding to five explicit
mental concepts, i.e., excellent, good, fair, poor, and bad. A newly designed
quality pooling is then applied to convert the qualitative labels into scores.
The classification framework is not only much more natural than the regression
based models, but also robust to the small sample size problem. Thorough
experiments are conducted on popular databases to verify the model's
effectiveness, efficiency, and robustness.
PMID- 25122843
TI - The Connection Between Bayesian Estimation of a Gaussian Random Field and RKHS.
AB - Reconstruction of a function from noisy data is key in machine learning and is
often formulated as a regularized optimization problem over an infinite
dimensional reproducing kernel Hilbert space (RKHS). The solution suitably
balances adherence to the observed data and the corresponding RKHS norm. When the
data fit is measured using a quadratic loss, this estimator has a known
statistical interpretation. Given the noisy measurements, the RKHS estimate
represents the posterior mean (minimum variance estimate) of a Gaussian random
field with covariance proportional to the kernel associated with the RKHS. In
this brief, we provide a statistical interpretation when more general losses are
used, such as absolute value, Vapnik or Huber. Specifically, for any finite set
of sampling locations (that includes where the data were collected), the maximum
a posteriori estimate for the signal samples is given by the RKHS estimate
evaluated at the sampling locations. This connection establishes a firm
statistical foundation for several stochastic approaches used to estimate unknown
regularization parameters. To illustrate this, we develop a numerical scheme that
implements a Bayesian estimator with an absolute value loss. This estimator is
used to learn a function from measurements contaminated by outliers.
PMID- 25122844
TI - Adaptive Output-Feedback Neural Control of Switched Uncertain Nonlinear Systems
With Average Dwell Time.
AB - This paper investigates the problem of adaptive neural tracking control via
output-feedback for a class of switched uncertain nonlinear systems without the
measurements of the system states. The unknown control signals are approximated
directly by neural networks. A novel adaptive neural control technique for the
problem studied is set up by exploiting the average dwell time method and
backstepping. A switched filter and different update laws are designed to reduce
the conservativeness caused by adoption of a common observer and a common update
law for all subsystems. The proposed controllers of subsystems guarantee that all
closed-loop signals remain bounded under a class of switching signals with
average dwell time, while the output tracking error converges to a small
neighborhood of the origin. As an application of the proposed design method,
adaptive output feedback neural tracking controllers for a mass-spring-damper
system are constructed.
PMID- 25122845
TI - Discrete-Time Zhang Neural Network for Online Time-Varying Nonlinear Optimization
With Application to Manipulator Motion Generation.
AB - In this brief, a discrete-time Zhang neural network (DTZNN) model is first
proposed, developed, and investigated for online time-varying nonlinear
optimization (OTVNO). Then, Newton iteration is shown to be derived from the
proposed DTZNN model. In addition, to eliminate the explicit matrix-inversion
operation, the quasi-Newton Broyden-Fletcher-Goldfarb-Shanno (BFGS) method is
introduced, which can effectively approximate the inverse of Hessian matrix. A
DTZNN-BFGS model is thus proposed and investigated for OTVNO, which is the
combination of the DTZNN model and the quasi-Newton BFGS method. In addition,
theoretical analyses show that, with step-size h=1 and/or with zero initial
error, the maximal residual error of the DTZNN model has an O(tau(2)) pattern,
whereas the maximal residual error of the Newton iteration has an O(tau) pattern,
with tau denoting the sampling gap. Besides, when h ? 1 and h ? (0,2) , the
maximal steady-state residual error of the DTZNN model has an O(tau(2)) pattern.
Finally, an illustrative numerical experiment and an application example to
manipulator motion generation are provided and analyzed to substantiate the
efficacy of the proposed DTZNN and DTZNN-BFGS models for OTVNO.
PMID- 25122846
TI - Temporal and spatial monitoring and prediction of epidemic outbreaks.
AB - This paper introduces a nonlinear dynamic model to study spatial and temporal
dynamics of epidemics of susceptible-infected-removed type. It involves modeling
the respective collections of epidemic states and syndromic observations as
random finite sets. Each epidemic state consists of the number of infected
individuals in an isolated population system and the corresponding partially
known parameters of the epidemic model. The infectious disease could spread
between population systems with known probabilities based on prior knowledge of
ecological and biological features of the environment. The problem is then
formulated in the context of Bayesian framework and estimated via a probability
hypothesis density filter. Each population system under surveillance is assumed
to be homogenous and fixed, with daily reports on the number of infected people
available for monitoring and prediction. When model parameters are partially
known, results of numerical studies indicate that the proposed approach can help
early prediction of the epidemic in terms of peak and duration.
PMID- 25122847
TI - Global asymptotic stabilization using adaptive fuzzy PD control.
AB - It is well-known that standard adaptive fuzzy control (AFC) can only guarantee
uniformly ultimately bounded stability due to inherent fuzzy approximation errors
(FAEs). This paper proves that standard AFC with proportional-derivative (PD)
control can guarantee global asymptotic stabilization even in the presence of
FAEs for a class of uncertain affine nonlinear systems. Variable-gain PD control
is designed to globally stabilize the plant. An optimal FAE is shown to be
bounded by the norm of the plant state vector multiplied by a globally invertible
and nondecreasing function, which provides a pivotal property for stability
analysis. Without discontinuous control compensation, the closed-loop system
achieves global and partially asymptotic stability in the sense that all plant
states converge to zero. Compared with previous adaptive approximation-based
global/asymptotic stabilization approaches, the major advantage of our approach
is that global stability and asymptotic stabilization are achieved concurrently
by a much simpler control law. Illustrative examples have further verified the
theoretical results.
PMID- 25122848
TI - On fuzzy sampled-data control of chaotic systems via a time-dependent Lyapunov
functional approach.
AB - In this paper, a novel approach to fuzzy sampled-data control of chaotic systems
is presented by using a time-dependent Lyapunov functional. The advantage of the
new method is that the Lyapunov functional is continuous at sampling times but
not necessarily positive definite inside the sampling intervals. Compared with
the existing works, the constructed Lyapunov functional makes full use of the
information on the piecewise constant input and the actual sampling pattern. In
terms of a new parameterized linear matrix inequality (LMI) technique, a less
conservative stabilization condition is derived to guarantee the exponential
stability for the closed-loop fuzzy sampled-data system. By solving a set of
LMIs, the fuzzy sampled-data controller can be easily obtained. Finally, the
chaotic Lorenz system and Rossler's system are employed to illustrate the
feasibility and effectiveness of the proposed method.
PMID- 25122849
TI - Feature selection in supervised saliency prediction.
AB - There is an increasing interest in learning mappings from features to saliency
maps based on human fixation data on natural images. These models have achieved
better results than most bottom-up (unsupervised) saliency models. However, they
usually use a large set of features trying to account for all possible saliency
related factors, which increases time cost and leaves the truly effective
features unknown. Through supervised feature selection, we show that the features
used in existing models are highly redundant. On each of three benchmark datasets
considered in this paper, a small number of features are found to be good enough
for predicting human eye fixations in free viewing experiments. The resulting
model achieves comparable results to that with all features and outperforms the
state-of-the-art models on these datasets. In addition, both the features
selected and the model trained on any dataset exhibit good performance on the
other two datasets, indicating robustness of the selected features and models
across different datasets. Finally, after training on a dataset for two different
tasks, eye fixation prediction and salient object detection, the selected
features show robustness across the two tasks. Taken together, these findings
suggest that a small set of features could account for visual saliency.
PMID- 25122850
TI - Model learning and knowledge sharing for a multiagent system with Dyna-Q
learning.
AB - In a multiagent system, if agents' experiences could be accessible and assessed
between peers for environmental modeling, they can alleviate the burden of
exploration for unvisited states or unseen situations so as to accelerate the
learning process. Since how to build up an effective and accurate model within a
limited time is an important issue, especially for complex environments, this
paper introduces a model-based reinforcement learning method based on a tree
structure to achieve efficient modeling and less memory consumption. The proposed
algorithm tailored a Dyna-Q architecture to multiagent systems by means of a tree
structure for modeling. The tree-model built from real experiences is used to
generate virtual experiences such that the elapsed time in learning could be
reduced. As well, this model is suitable for knowledge sharing. This paper is
inspired by the concept of knowledge sharing methods in multiagent systems where
an agent could construct a global model from scattered local models held by
individual agents. Consequently, it can increase modeling accuracy so as to
provide valid simulated experiences for indirect learning at the early stage of
learning. To simplify the sharing process, the proposed method applies resampling
techniques to grafting partial branches of trees containing required and useful
experiences disseminated from experienced peers, instead of merging the whole
trees. The simulation results demonstrate that the proposed sharing method can
achieve the objectives of sample efficiency and learning acceleration in
multiagent cooperation applications.
PMID- 25122851
TI - A video, text, and speech-driven realistic 3-d virtual head for human-machine
interface.
AB - A multiple inputs-driven realistic facial animation system based on 3-D virtual
head for human-machine interface is proposed. The system can be driven
independently by video, text, and speech, thus can interact with humans through
diverse interfaces. The combination of parameterized model and muscular model is
used to obtain a tradeoff between computational efficiency and high realism of 3
D facial animation. The online appearance model is used to track 3-D facial
motion from video in the framework of particle filtering, and multiple
measurements, i.e., pixel color value of input image and Gabor wavelet
coefficient of illumination ratio image, are infused to reduce the influence of
lighting and person dependence for the construction of online appearance model.
The tri-phone model is used to reduce the computational consumption of visual co
articulation in speech synchronized viseme synthesis without sacrificing any
performance. The objective and subjective experiments show that the system is
suitable for human-machine interaction.
PMID- 25122852
TI - Multilayer obstacle-avoiding x-architecture steiner minimal tree construction
based on particle swarm optimization.
AB - As the basic model for very large scale integration routing, the Steiner minimal
tree (SMT) can be used in various practical problems, such as wire length
optimization, congestion, and time delay estimation. In this paper, an effective
algorithm based on particle swarm optimization is presented to construct a
multilayer obstacle-avoiding X-architecture SMT (ML-OAXSMT). First, a
pretreatment strategy is presented to reduce the total number of judgments for
the routing conditions around obstacles and vias. Second, an edge transformation
strategy is employed to make the particles have the ability to bypass the
obstacles while the union-find partition is used to prevent invalid solutions.
Third, according to the feature of ML-OAXSMT problem, we design an edge-vertex
encoding strategy, which has the advantage of simple and effective. Moreover, a
penalty mechanism is proposed to help the particle bypass the obstacles, and
reduce the generation of via at the same time. Experimental results show that our
algorithm from a global perspective of multilayer structure can achieve the best
solution quality among the existing algorithms. Finally, to our best knowledge,
we redefine the edge cost and then construct the obstacle-avoiding preferred
direction X-architecture Steiner tree, which is the first work to address this
problem and can offer the theory supports for chip design based on non-Manhattan
architecture.
PMID- 25122853
TI - Poor performance of the determine HIV-1/2 Ag/Ab combo fourth-generation rapid
test for detection of acute infections in a National Household Survey in
Swaziland.
AB - Fourth-generation HIV rapid tests (RTs) claim to detect both p24 antigen (Ag) and
HIV antibodies (Ab) for early identification of acute infections, important for
targeting prevention and reducing HIV transmission. In a nationally
representative household survey in Swaziland, 18,172 adults, age 18 to 49 years,
received home-based HIV rapid testing in 2010 and 2011. Of the 18,172
individuals, 5,822 (32.0%) were Ab positive (Ab(+)) by the Determine HIV-1/2
Ab/Ab combo test, and 5,789 (99.4%) of those were confirmed to be reactive in the
Uni-Gold test. Determine combo identified 12 individuals as having acute
infections (Ag(+)/Ab negative [Ab(-)]); however, none had detectable HIV-1 RNA
and 8 of 12 remained HIV negative at their 6-week follow-up visit (4 were lost to
follow-up). All RT-nonreactive samples were pooled and tested by nucleic acid
amplification testing (NAAT) to identify acute infections. NAAT identified 13
(0.1%) of the 12,338 HIV antibody-negative specimens as HIV RNA positive, with
RNA levels ranging from 300 to >10,000,000 copies/ml. However, none of them were
Ag(+) by Determine combo. Follow-up testing of 12 of the 13 NAAT-positive
individuals at 6 months demonstrated 12 seroconversions (1 individual was lost to
follow-up). Therefore, the Determine combo test had a sensitivity of 0% (95%
confidence interval, 0 to 28) and positive predictive value of 0% for the
detection of acute infections. The ability of the 4th-generation Determine combo
to detect antigen was very poor in Swaziland. Thus, the Determine combo test does
not add any value to the current testing algorithm; rather, it adds additional
costs and complexity to HIV diagnosis. The detection of acute HIV infections may
need to rely on other testing strategies.
PMID- 25122855
TI - Comparison of flocked and aptima swabs and two specimen transport media in the
aptima combo 2 assay.
AB - Self-collected vaginal Aptima swabs and flocked swabs in Aptima specimen
transport medium and ESwabs in ESwab medium detected all 37 Chlamydia trachomatis
infected patients from 287 women tested by the Aptima Combo assay. Prevalence
rates of C. trachomatis, Neisseria gonorrhoeae, and dual infection were 12.8%,
3.1%, and 2.4%, respectively.
PMID- 25122856
TI - Mupirocin-induced mutations in ileS in various genetic backgrounds of methicillin
resistant Staphylococcus aureus.
AB - Topical mupirocin is widely used for the decolonization of methicillin-resistant
Staphylococcus aureus (MRSA) carriers. We evaluated the capacity of various MRSA
clonotypes to develop mutations in the ileS gene associated with low-level
mupirocin resistance. Twenty-four mupirocin-sensitive MRSA isolates from a
variety of genotypes (determined by a multilocus variable-number tandem-repeat
assay) were selected. Mupirocin MICs were determined by Etest. The isolates were
then incubated in subinhibitory concentrations of mupirocin for 7 to 14 days.
Repeat MIC determinations and sequencing of the ileS gene were then performed.
Doubling times of isolates exposed to mupirocin and of unexposed isolates were
compared. We found that exposure to mupirocin led to rapid induction of low-level
resistance (MICs of 8 to 24 MUg/ml) in 11 of 24 (46%) MRSA isolates. This
phenomenon was observed in strains with diverse genetic backgrounds. Various
mutations were detected in 18 of 24 (75%) MRSA isolates. Acquisition of mutations
appeared to be a stepwise process during prolonged incubation with the drug.
Among the five isolates exhibiting low-level resistance and the highest MICs,
four tested sensitive after incubation in the absence of mupirocin but there was
no reversion to the susceptible wild-type primary sequence. Resistance was not
associated with significant fitness cost, suggesting that MRSA strains with low
level mupirocin resistance may have a selective advantage in facilities where
mupirocin is commonly used. Our findings emphasize the importance of the
judicious use of this topical agent and the need to closely monitor for the
emergence of resistance.
PMID- 25122854
TI - PCR in diagnosis of invasive aspergillosis: a meta-analysis of diagnostic
performance.
AB - Invasive aspergillosis is a difficult-to-diagnose infection with a high mortality
rate that affects high-risk groups such as patients with neutropenia and
hematologic malignancies. We performed a bivariate meta-analysis of diagnostic
data for an Aspergillus sp. PCR assay with blood specimens from high-risk
hematology patients. We included all studies involving human subjects that
assessed the performance of any PCR assay for invasive aspergillosis in whole
blood or serum and that used the European Organization for the treatment of
Cancer/Mycoses Study Group criteria as a reference standard. Three investigators
independently searched the literature for eligible studies and extracted the
data. Out of a total of 37 studies, 25 met strict quality criteria and were
included in our evidence synthesis. Twenty-five studies with 2,595 patients were
analyzed. The pooled diagnostic performance of whole-blood and serum PCR assays
was moderate, with a sensitivity and specificity of 84% (95% confidence interval
[CI], 75 to 91%) and 76% (95% CI, 65 to 84%), respectively, suggesting that a
positive or negative result is unable, on its own, to confirm or exclude a
suspected infection. The performance of a PCR assay of serum was not
significantly different from that of whole blood. Notably, at least two positive
PCR test results were found to have a specificity of 95% and a sensitivity of 64%
for invasive infection, achieving a high positive likelihood ratio of 12.8.
Importantly, the European Aspergillus PCR Initiative (EAPCRI) recommendations
improved the performance of the PCR even further when at least two positive
specimens were used to define PCR positivity. In conclusion, two positive PCR
results should be considered highly indicative of an active Aspergillus sp.
infection. Use of the EAPCRI recommendations by clinical laboratories can further
enhance PCR performance.
PMID- 25122857
TI - Evaluation of the nanosphere Verigene BC-GN assay for direct identification of
gram-negative bacilli and antibiotic resistance markers from positive blood
cultures and potential impact for more-rapid antibiotic interventions.
AB - The Verigene BC-GN assay correctly identified all 51 Gram-negative bacilli (GNB)
from positive blood cultures and all 14 carbapenemase enzymes tested. The assay
gave organism identification (ID) results an average of 24 h faster compared to
conventional identifications. Medical management could have been modified for
31.8% of patients an average 33 h sooner. In conclusion, the BC-GN assay is a
very accurate, rapid assay which would allow for more-immediate medical
management decisions in patients with bacteremia from GNB.
PMID- 25122858
TI - Two cases of bacteriemia caused by nontoxigenic, non-O1, non-O139 Vibrio cholerae
isolates in Ho Chi Minh City, Vietnam.
AB - The toxigenic bacterium Vibrio cholerae belonging to the O1 and O139 serogroups
is commonly associated with epidemic diarrhea in tropical settings; other
diseases caused by this environmental pathogen are seldom identified. Here we
report two unassociated cases of nonfatal, nontoxigenic V. cholerae non-O1, non
O139 bacteremia in patients with comorbidities in Ho Chi Minh City, Vietnam, that
occurred within a 4-week period.
PMID- 25122860
TI - Generation of calves persistently infected with HoBi-like pestivirus and
comparison of methods for detection of these persistent infections.
AB - The identification and elimination of persistently infected (PI) cattle are the
most effective measures for controlling bovine pestiviruses, including bovine
viral diarrhea virus (BVDV) and the emerging HoBi-like viruses. Here, colostrum
deprived calves persistently infected with HoBi-like pestivirus (HoBi-like PI
calves) were generated and sampled (serum, buffy coat, and ear notches) on the
day of birth (DOB) and weekly for 5 consecutive weeks. The samples were subjected
to diagnostic tests for BVDV--two reverse transcriptase PCR (RT-PCR) assays, two
commercial real-time RT quantitative PCR (RT-qPCR), two antigen capture enzyme
linked immunosorbent assays (ACE), and immunohistochemistry (IHC)--and to HoBi
like virus-specific RT-PCR and RT-qPCR assays. The rate of false negatives varied
among the calves. The HoBi-like virus-specific RT-PCR detected HoBi-like virus in
83%, 75%, and 87% of the serum, buffy coat, and ear notch samples, respectively,
while the HoBi-like RT-qPCR detected the virus in 83%, 96%, and 62%,
respectively. In comparison, the BVDV RT-PCR test had a higher rate of false
negatives in all tissue types, especially for the ear notch samples (missing
detection in at least 68% of the samples). The commercial BVDV RT-qPCRs and IHC
detected 100% of the ear notch samples as positive. While ACE based on the BVDV
glycoprotein E(rns) detected infection in at least 87% of ear notches, no
infections were detected using NS3-based ACE. The BVDV RT-qPCR, ACE, and IHC
yielded higher levels of detection than the HoBi-like virus-specific assays,
although the lack of differentiation between BVDV and HoBi-like viruses would
make these tests of limited use for the control and/or surveillance of persistent
HoBi-like virus infection. An improvement in HoBi-like virus tests is required
before a reliable HoBi-like PI surveillance program can be designed.
PMID- 25122859
TI - Laboratory detection of Clostridium difficile in piglets in Australia.
AB - Clostridium difficile is a well-known enteric pathogen of humans and the
causative agent of high-morbidity enteritis in piglets aged 1 to 7 days. C.
difficile prevalence in Australian piglets is as high as 70%. The current
diagnostic assays have been validated only for human infections, and there are no
published studies assessing their performance in Australian piglets. We evaluated
the suitability of five assays for detecting C. difficile in 157 specimens of
piglet feces. The assays included a loop-mediated isothermal amplification (LMIA)
PCR for tcdA (illumigene C. difficile; Meridian), a real-time PCR for tcdB
(GeneOhm Cdiff; Becton Dickinson), two-component enzyme immunoassays (EIA) for C.
difficile glutamate dehydrogenase (GDH) (EIA-GDH) and TcdA/TcdB (EIA-TcdA/TcdB)
(C. diff Quik Chek; Alere), and direct culture (DC) (C. difficile chromID agar;
bioMerieux). The assays for detection of the organism were compared against
enrichment culture (EC), and assays for detection of toxins/toxin genes were
compared against EC followed by PCR for toxin genes (toxigenic EC [TEC]). The
recovery of C. difficile by EC was 39.5% (n = 62/157), and TEC revealed that
58.1% (n = 36/62) of isolates were positive for at least one toxin gene
(tcdA/tcdB). Compared with those for EC/TEC, the sensitivities, specificities,
positive predictive values, and negative predictive values were, respectively, as
follows: DC, 91.9, 100.0, 100.0, and 95.0%; EIA-GDH, 41.9, 92.6, 78.8, and 71.0%;
EIA-TcdA/TcdB, 5.6, 99.2, 66.7, and 77.9%; real-time PCR, 42.9, 96.7, 78.9, and
85.4% and LMIA-PCR, 25.0, 95.9, 64.3, and 81.1%. The performance of the molecular
methods was poor, suggesting that the current commercially available assays for
diagnosis of C. difficile in humans are not suitable for use in piglets. C.
difficile recovery by the DC provides a cost-effective alternative.
PMID- 25122861
TI - Comparative evaluation of three commercial systems for detection of high-risk
human papillomavirus in cervical and vaginal ThinPrep PreservCyt samples and
correlation with biopsy results.
AB - Genital human papillomavirus (HPV) is the etiologic agent of more than 99% of all
cervical cancers worldwide, with 14 genotypes being considered oncogenic or "high
risk" because of their association with severe dysplasia and cervical carcinoma.
Among these 14 high-risk types, HPV-16 and -18 account for approximately 70% of
cervical cancers. The aim of this study was to evaluate three FDA-approved HPV
nucleic acid-based tests for the ability to predict high-grade cervical
intraepithelial neoplasias (CIN2 or worse) in corresponding tissue biopsy
specimens. Residual specimens (total n = 793, cervical n = 743, vaginal n = 50)
collected in ThinPrep PreservCyt medium with a cytologic result of >= atypical
squamous cells of undetermined significance were tested by the Hybrid Capture 2
(HC2) assay (Qiagen, Gaithersburg, MD), the cobas HPV test (Roche Diagnostics,
Indianapolis, IN), and the APTIMA HPV assay (Hologic, San Diego, CA). Genotyping
for HPV-16 and HPV-18 was simultaneously performed by the cobas HPV test. Results
were compared to cervical or vaginal biopsy findings, when they were available (n
= 350). Among the 350 patients with corresponding biopsy results, 81 (23.1%)
showed >= CIN2 by histopathology. The >= CIN2 detection sensitivity was 91.4% by
the cobas and APTIMA assays and 97.5% by HC2 assay. The specificities of the
cobas, APTIMA, and HC2 assays were 31.2, 42.0, and 27.1%, respectively. When
considering only positive HPV-16 and/or HPV-18 genotype results, the cobas test
showed a sensitivity and a specificity of 51.9 and 86.6%, respectively. While the
HC2, cobas, and APTIMA assays showed similar sensitivities for the detection of
>= CIN2 lesions, the specificities of the three tests varied, with the greatest
specificity (86.6%) observed when the HPV-16 and/or HPV-18 genotypes were
detected.
PMID- 25122863
TI - Evaluation of disk potentiation test using kirby-bauer disks containing high
dosage fosfomycin and glucose-6-phosphate to detect production of glutathione S
transferase responsible for fosfomycin resistance.
PMID- 25122862
TI - Collection and characterization of samples for establishment of a serum
repository for lyme disease diagnostic test development and evaluation.
AB - Serological assays and a two-tiered test algorithm are recommended for laboratory
confirmation of Lyme disease. In the United States, the sensitivity of two-tiered
testing using commercially available serology-based assays is dependent on the
stage of infection and ranges from 30% in the early localized disease stage to
near 100% in late-stage disease. Other variables, including subjectivity in
reading Western blots, compliance with two-tiered recommendations, use of
different first- and second-tier test combinations, and use of different test
samples, all contribute to variation in two-tiered test performance. The
availability and use of sample sets from well-characterized Lyme disease patients
and controls are needed to better assess the performance of existing tests and
for development of improved assays. To address this need, the Centers for Disease
Control and Prevention and the National Institutes of Health prospectively
collected sera from patients at all stages of Lyme disease, as well as healthy
donors and patients with look-alike diseases. Patients and healthy controls were
recruited using strict inclusion and exclusion criteria. Samples from all
included patients were retrospectively characterized by two-tiered testing. The
results from two-tiered testing corroborated the need for novel and improved
diagnostics, particularly for laboratory diagnosis of earlier stages of
infection. Furthermore, the two-tiered results provide a baseline with samples
from well-characterized patients that can be used in comparing the sensitivity
and specificity of novel diagnostics. Panels of sera and accompanying clinical
and laboratory testing results are now available to Lyme disease serological test
users and researchers developing novel tests.
PMID- 25122864
TI - Predictive value of testing nasopharyngeal samples for respiratory viruses in the
setting of lower respiratory tract disease.
AB - To determine the predictive value of nasopharyngeal (NP) sample testing for
respiratory viruses (RVs) in suspected lower respiratory tract disease, 72 paired
NP and bronchoalveolar lavage (BAL) fluid specimen sets, mostly from transplant
recipients or patients with hematologic malignancies, were analyzed. Overall,
31.3% of the specimens tested positive for an RV. In 19 sets (26.4%), the NP and
BAL fluid specimens were both positive for an RV; in 3 sets (4.2%), the NP
specimens were positive but the BAL fluid specimens were negative; and in 3 other
sets, the NP specimens were negative but the BAL fluid specimens were positive.
The positive and negative predictive values of the NP specimens were 86.4% and
94%, respectively.
PMID- 25122865
TI - Mutational analysis of Pneumocystis jirovecii dihydropteroate synthase and
dihydrofolate reductase genes in HIV-infected patients in China.
AB - We investigated Pneumocystis jirovecii dihydropteroate synthase (DHPS) and
dihydrofolate reductase (DHFR) genes for mutations in 25 Chinese HIV-infected
patients with P. jirovecii pneumonia. We identified DHPS mutations in 3 (12%)
patients and DHFR mutations in 1 (4%) patient. The prevalence of DHPS and DHFR
mutations in China remains low, as it does in other developing countries.
PMID- 25122866
TI - Clinical characteristics of patients who test positive for Clostridium difficile
by repeat PCR.
AB - The high sensitivity of PCR assays for diagnosing Clostridium difficile infection
(CDI) has greatly reduced the need for repeat testing after a negative result.
Nevertheless, a small subset of patients do test positive within 7 days of a
negative test. The aim of this study was to evaluate the clinical characteristics
of these patients to determine when repeat testing may be appropriate. The
results of all Xpert C. difficile PCR (Cepheid, Sunnyvale CA) tests performed in
the clinical microbiology laboratory at New York-Presbyterian Hospital, Columbia
University Medical Center (NYPH/CUMC) from 1 May 2011 through 6 September 2013,
were reviewed. A retrospective case-control study was performed, comparing
patients who tested positive within 7 days of a negative test result to a random
selection of 50 controls who tested negative within 7 days of a negative test
result. During the study period, a total of 14,875 tests were performed, of which
1,066 were repeat tests (7.2%). Eleven of these repeat tests results were
positive (1.0%). The only risk factor independently associated with repeat
testing positive was history of a prior CDI (odds ratio [OR], 19.6 [95%
confidence interval {CI}, 4.0 to 19.5], P < 0.001). We found that patients who
test positive for C. difficile by PCR within 7 days of a negative test are more
likely to have a history of CDI than are patients who test negative with repeat
PCR. This finding may be due to the high rate of disease relapse or the increased
likelihood of empirical therapy leading to false-negative results in these
patients.
PMID- 25122867
TI - Systematic review of health outcomes in relation to salt intake highlights the
widening divide between guidelines and the evidence.
PMID- 25122868
TI - Sodium and cardiovascular disease: what the data show.
PMID- 25122869
TI - Graudal et al. article on sodium intake should include ethnic disclaimer.
PMID- 25122870
TI - Response to "Article on sodium intake should include ethnic disclaimer".
PMID- 25122875
TI - The central importance of the cytoskeleton for increased cell stiffness in
cardiovascular disease. Focus on "Diabetes increases stiffness of live
cardiomyocytes measured by atomic force microscopy nanoindentation".
PMID- 25122874
TI - Biomechanical strain vehicles for fibroblast-directed skeletal myoblast
differentiation and myotube functionality in a novel coculture.
AB - Skeletal muscle functionality is governed by multiple stimuli, including
cytokines and biomechanical strain. Fibroblasts embedded within muscle connective
tissue respond to biomechanical strain by secreting cytokines that induce
myoblast differentiation and, we hypothesize, regulate myotube function. A
coculture was established to allow cross talk between fibroblasts in Bioflex
wells and myoblasts on nondeformable coverslips situated above Bioflex wells.
Cyclic short-duration strain (CSDS) modeling repetitive stress/injury, acyclic
long-duration strain (ALDS) modeling manipulative therapy, and combined strain
paradigms (CSDS + ALDS) were applied to fibroblasts. Nonstrained myoblasts in
uniculture and coculture served as controls. After fibroblasts had induced
myoblast differentiation, myotube contraction was assessed by perfusion of ACh
(10(-11)-10(-3) M). CSDS-treated fibroblasts increased myotube contractile
sensitivity vs. uniculture (P < 0.05). As contraction is dependent on ACh
binding, expression and clustering of nicotinic ACh receptors (nAChRs) were
measured. CSDS-treated fibroblasts increased nAChR expression (P < 0.05), which
correlated with myotube contraction. ALDS-treated fibroblasts did not
significantly affect contraction or nAChR expression. Agrin-treated myotubes were
then used to design a computer algorithm to identify alpha-bungarotoxin-stained
nAChR clusters. ALDS-treated fibroblasts increased nAChR clustering (P < 0.05),
while CSDS-treated fibroblasts disrupted cluster formation. CSDS-treated
fibroblasts produced nAChRs preferentially located in nonclustered regions (P <
0.05). Strain-activated fibroblasts mediate myotube differentiation with multiple
functional phenotypes. Similar to muscle injury, CSDS-treated fibroblasts
disrupted nAChR clusters and hypersensitized myotube contraction, while ALDS
treated fibroblasts aggregated nAChRs in large clusters, which may have important
clinical implications. Cellular strategies aimed at improving muscle
functionality, such as through biomechanical strain vehicles that activate
fibroblasts to stabilize postsynaptic nAChRs on nearby skeletal muscle, may serve
as novel targets in neuromuscular disorders.
PMID- 25122877
TI - Making the cut: analytical and empirical bioethics.
PMID- 25122878
TI - Surgical castration, coercive offers and coercive effects: it is still not about
consent.
PMID- 25122880
TI - Understanding the basis of antibiotic resistance: a platform for drug discovery.
AB - There are numerous genes in Salmonella enterica serovar Typhimurium that can
confer resistance to fluoroquinolone antibiotics, including those that encode
topoisomerase proteins, the primary targets of this class of drugs. However,
resistance is often multifactorial in clinical isolates and it is not uncommon to
also detect mutations in genes that affect the expression of proteins involved in
permeability and multi-drug efflux. The latter mechanism, mediated by tripartite
efflux systems, such as that formed by the AcrAB-TolC system, confers inherent
resistance to many antibiotics, detergents and biocides. Genetic inactivation of
efflux genes gives multi-drug hyper-susceptibility, and in the absence of an
intact AcrAB-TolC system some chromosomal and transmissible antibiotic resistance
genes no longer confer clinically relevant levels of resistance. Furthermore, a
functional multi-drug resistance efflux pump, such as AcrAB-TolC, is required for
virulence and the ability to form a biofilm. In part, this is due to altered
expression of virulence and biofilm genes being sensitive to efflux status.
Efflux pump expression can be increased, usually due to mutations in regulatory
genes, and this confers resistance to clinically useful drugs such as
fluoroquinolones and beta-lactams. Here, I discuss some of the work my team has
carried out characterizing the mechanisms of antibiotic resistance in Salmonella
enterica serovar Typhimurium from the late 1980s to 2014. A video of this Prize
Lecture, presented at the Society for General Microbiology Annual Conference
2014, can be viewed via this link: https://www.youtube.com/watch?v=MCRumMV99Yw.
PMID- 25122881
TI - Toward a better understanding of the injured hippocampus: multimodal imaging in
functionally relevant substructures.
PMID- 25122876
TI - ABCG2pos lung mesenchymal stem cells are a novel pericyte subpopulation that
contributes to fibrotic remodeling.
AB - Genesis of myofibroblasts is obligatory for the development of pathology in many
adult lung diseases. Adult lung tissue contains a population of perivascular
ABCG2(pos) mesenchymal stem cells (MSC) that are precursors of myofibroblasts and
distinct from NG2 pericytes. We hypothesized that these MSC participate in
deleterious remodeling associated with pulmonary fibrosis (PF) and associated
hypertension (PH). To test this hypothesis, resident lung MSC were quantified in
lung samples from control subjects and PF patients. ABCG2(pos) cell numbers were
decreased in human PF and interstitial lung disease compared with control
samples. Genetic labeling of lung MSC in mice enabled determination of terminal
lineage and localization of ABCG2 cells following intratracheal administration of
bleomycin to elicit fibrotic lung injury. Fourteen days following bleomycin
injury enhanced green fluorescent protein (eGFP)-labeled lung MSC-derived cells
were increased in number and localized to interstitial areas of fibrotic and
microvessel remodeling. Finally, gene expression analysis was evaluated to define
the response of MSC to bleomycin injury in vivo using ABCG2(pos) MSC isolated
during the inflammatory phase postinjury and in vitro bleomycin or transforming
growth factor-beta1 (TGF-beta1)-treated cells. MSC responded to bleomycin
treatment in vivo with a profibrotic gene program that was not recapitulated in
vitro with bleomycin treatment. However, TGF-beta1 treatment induced the
appearance of a profibrotic myofibroblast phenotype in vitro. Additionally, when
exposed to the profibrotic stimulus, TGF-beta1, ABCG2, and NG2 pericytes
demonstrated distinct responses. Our data highlight ABCG2(pos) lung MSC as a
novel cell population that contributes to detrimental myofibroblast-mediated
remodeling during PF.
PMID- 25122882
TI - Evolutionarily conserved mechanisms in calcium handling may underlie intrinsic
sensitivity to dopaminergic neuron death.
PMID- 25122885
TI - Electrophysiological correlates of voice learning and recognition.
AB - Listeners can recognize familiar human voices from variable utterances,
suggesting the acquisition of speech-invariant voice representations during
familiarization. However, the neurocognitive mechanisms mediating learning and
recognition of voices from natural speech are currently unknown. Using
electrophysiology, we investigated how representations are formed during
intentional learning of initially unfamiliar voices that were later recognized
among novel voices. To probe the acquisition of speech-invariant voice
representations, we compared a "same sentence" condition, in which speakers
repeated the study utterances at test, and a "different sentence" condition.
Although recognition performance was higher for same compared with different
sentences, substantial voice learning also occurred for different sentences, with
recognition performance increasing across consecutive study-test-cycles. During
study, event-related potentials elicited by voices subsequently remembered
elicited a larger sustained parietal positivity (~250-1400 ms) compared with
subsequently forgotten voices. This difference due to memory was unaffected by
test sentence condition and may thus reflect the acquisition of speech-invariant
voice representations. At test, voices correctly classified as "old" elicited a
larger late positive component (300-700 ms) at Pz than voices correctly
classified as "new." This event-related potential OLD/NEW effect was limited to
the same sentence condition and may thus reflect speech-dependent retrieval of
voices from episodic memory. Importantly, a speech-independent effect for learned
compared with novel voices was found in beta band oscillations (16-17 Hz) between
290 and 370 ms at central and right temporal sites. Our results are a first step
toward elucidating the electrophysiological correlates of voice learning and
recognition.
PMID- 25122883
TI - Damage to the Salience Network and interactions with the Default Mode Network.
AB - Interactions between the Salience Network (SN) and the Default Mode Network (DMN)
are thought to be important for cognitive control. However, evidence for a causal
relationship between the networks is limited. Previously, we have reported that
traumatic damage to white matter tracts within the SN predicts abnormal DMN
function. Here we investigate the effect of this damage on network interactions
that accompany changing motor control. We initially used fMRI of the Stop Signal
Task to study response inhibition in humans. In healthy subjects, functional
connectivity (FC) between the right anterior insula (rAI), a key node of the SN,
and the DMN transiently increased during stopping. This change in FC was not seen
in a group of traumatic brain injury (TBI) patients with impaired cognitive
control. Furthermore, the amount of SN tract damage negatively correlated with FC
between the networks. We confirmed these findings in a second group of TBI
patients. Here, switching rather than inhibiting a motor response: (1) was
accompanied by a similar increase in network FC in healthy controls; (2) was not
seen in TBI patients; and (3) tract damage after TBI again correlated with FC
breakdown. This shows that coupling between the rAI and DMN increases with
cognitive control and that damage within the SN impairs this dynamic network
interaction. This work provides compelling evidence for a model of cognitive
control where the SN is involved in the attentional capture of salient external
stimuli and signals the DMN to reduce its activity when attention is externally
focused.
PMID- 25122886
TI - An amplitude modulation/demodulation scheme for whisker-based texture perception.
AB - Whisking rodents can discriminate finely textured objects using their vibrissae.
The biomechanical and neural processes underlying such sensory tasks remain
elusive. Here we combine the use of model micropatterned substrates and high
resolution videography of rats' whiskers during tactile exploration to study how
texture information is mechanically encoded in the whisker motion. A
biomechanical modeling of the whisker is developed, which yields quantitative
predictions of the spectral and temporal characteristics of the observed whisker
kinetics, for any given topography. These texture-induced whisker vibrations are
then replayed via a multiwhisker stimulator while recording neuronal responses in
the barrel field of the primary somatosensory cortex (S1bf). These results
provide a comprehensive description of the transduction process at play during
fine texture sensing in rats. They suggest that the sensory system operates
through a vibratory amplitude modulation/demodulation scheme. Fine textural
properties are encoded in the time-varying envelope of the whisker-resonant
vibrations. This quantity is then recovered by neural demodulation, as it
effectively drives the spiking-rate signal of a large fraction of S1 cortical
neurons. This encoding/decoding scheme is shown to be robust against variations
in exploratory conditions, such as the scanning speed or pad-to-substrate
distance, thus allowing for reliable tactile discrimination in realistic
conditions.
PMID- 25122884
TI - Synaptic GluN2A and GluN2B containing NMDA receptors within the superficial
dorsal horn activated following primary afferent stimulation.
AB - NMDA receptors are important elements in pain signaling in the spinal cord dorsal
horn. They are heterotetramers, typically composed of two GluN1 and two of four
GluN2 subunits: GluN2A-2D. Mice lacking some of the GluN2 subunits show deficits
in pain transmission yet functional synaptic localization of these receptor
subtypes in the dorsal horn has not been fully resolved. In this study, we have
investigated the composition of synaptic NMDA receptors expressed in monosynaptic
and polysynaptic pathways from peripheral sensory fibers to lamina I neurons in
rats. We focused on substance P receptor-expressing (NK1R+) projection neurons,
critical for expression of hyperalgesia and allodynia. EAB-318 and (R)-CPP,
GluN2A/B antagonists, blocked both monosynaptic and polysynaptic NMDA EPSCs
initiated by primary afferent activation by ~90%. Physiological measurements
exploiting the voltage dependence of monosynaptic EPSCs similarly indicated
dominant expression of GluN2A/B types of synaptic NMDA receptors. In addition, at
synapses between C fibers and NK1R+ neurons, NMDA receptor activation initiated a
secondary, depolarizing current. Ifenprodil, a GluN2B antagonist, caused modest
suppression of monosynaptic NMDA EPSC amplitudes, but had a widely variable,
sometimes powerful, effect on polysynaptic responses following primary afferent
stimulation when inhibitory inputs were blocked to mimic neuropathic pain. We
conclude that GluN2B subunits are moderately expressed at primary afferent
synapses on lamina I NK1R+ neurons, but play more important roles for
polysynaptic NMDA EPSCs driven by primary afferents following disinhibition,
supporting the view that the analgesic effect of the GluN2B antagonist on
neuropathic pain is at least in part, within the spinal cord.
PMID- 25122887
TI - Deep brain stimulation abolishes slowing of reactions to unlikely stimuli.
AB - The cortico-basal-ganglia circuit plays a critical role in decision making on the
basis of probabilistic information. Computational models have suggested how this
circuit could compute the probabilities of actions being appropriate according to
Bayes' theorem. These models predict that the subthalamic nucleus (STN) provides
feedback that normalizes the neural representation of probabilities, such that if
the probability of one action increases, the probabilities of all other available
actions decrease. Here we report the results of an experiment testing a
prediction of this theory that disrupting information processing in the STN with
deep brain stimulation should abolish the normalization of the neural
representation of probabilities. In our experiment, we asked patients with
Parkinson's disease to saccade to a target that could appear in one of two
locations, and the probability of the target appearing in each location was
periodically changed. When the stimulator was switched off, the target
probability affected the reaction times (RT) of patients in a similar way to
healthy participants. Specifically, the RTs were shorter for more probable
targets and, importantly, they were longer for the unlikely targets. When the
stimulator was switched on, the patients were still faster for more probable
targets, but critically they did not increase RTs as the target was becoming less
likely. This pattern of results is consistent with the prediction of the model
that the patients on DBS no longer normalized their neural representation of
prior probabilities. We discuss alternative explanations for the data in the
context of other published results.
PMID- 25122888
TI - Exocytotic machineries of vestibular type I and cochlear ribbon synapses display
similar intrinsic otoferlin-dependent Ca2+ sensitivity but a different coupling
to Ca2+ channels.
AB - The hair cell ribbon synapses of the mammalian auditory and vestibular systems
differ greatly in their anatomical organization and firing properties. Notably,
vestibular Type I hair cells (VHC-I) are surrounded by a single calyx-type
afferent terminal that receives input from several ribbons, whereas cochlear
inner hair cells (IHCs) are contacted by several individual afferent boutons,
each facing a single ribbon. The specificity of the presynaptic molecular
mechanisms regulating transmitter release at these different sensory ribbon
synapses is not well understood. Here, we found that exocytosis during voltage
activation of Ca(2+) channels displayed higher Ca(2+) sensitivity, 10 mV more
negative half-maximum activation, and a smaller dynamic range in VHC-I than in
IHCs. VHC-I had a larger number of Ca(2+) channels per ribbon (158 vs 110 in
IHCs), but their Ca(2+) current density was twofold smaller because of a smaller
open probability and unitary conductance. Using confocal and stimulated emission
depletion immunofluorescence microscopy, we showed that VHC-I had fewer synaptic
ribbons (7 vs 17 in IHCs) to which Cav1.3 channels are more tightly organized
than in IHCs. Gradual intracellular Ca(2+) uncaging experiments revealed that
exocytosis had a similar intrinsic Ca(2+) sensitivity in both VHC-I and IHCs (KD
of 3.3 +/- 0.6 MUM and 4.0 +/- 0.7 MUM, respectively). In otoferlin-deficient
mice, exocytosis was largely reduced in VHC-I and IHCs. We conclude that VHC-I
and IHCs use a similar micromolar-sensitive otoferlin Ca(2+) sensor and that
their sensory encoding specificity is essentially determined by a different
functional organization of Ca(2+) channels at their synaptic ribbons.
PMID- 25122889
TI - Sensory-evoked and spontaneous gamma and spindle bursts in neonatal rat motor
cortex.
AB - Self-generated neuronal activity originating from subcortical regions drives
early spontaneous motor activity, which is a hallmark of the developing
sensorimotor system. However, the neural activity patterns and role of primary
motor cortex (M1) in these early movements are still unknown. Combining voltage
sensitive dye imaging (VSDI) with simultaneous extracellular multielectrode
recordings in postnatal day 3 (P3)-P5 rat primary somatosensory cortex (S1) and
M1 in vivo, we observed that tactile forepaw stimulation induced spindle bursts
in S1 and gamma and spindle bursts in M1. Approximately 40% of the spontaneous
gamma and spindle bursts in M1 were driven by early motor activity, whereas 23.7%
of the M1 bursts triggered forepaw movements. Approximately 35% of the M1 bursts
were uncorrelated to movements and these bursts had significantly fewer spikes
and shorter burst duration. Focal electrical stimulation of layer V neurons in M1
mimicking physiologically relevant 40 Hz gamma or 10 Hz spindle burst activity
reliably elicited forepaw movements. We conclude that M1 is already involved in
somatosensory information processing during early development. M1 is mainly
activated by tactile stimuli triggered by preceding spontaneous movements, which
reach M1 via S1. Only a fraction of M1 activity transients trigger motor
responses directly. We suggest that both spontaneously occurring and sensory
evoked gamma and spindle bursts in M1 contribute to the maturation of
corticospinal and sensorimotor networks required for the refinement of
sensorimotor coordination.
PMID- 25122890
TI - High-NaCl perception in Drosophila melanogaster.
AB - Salt is a fundamental nutrient that is required for many physiological processes,
including electrolyte homeostasis and neuronal activity. In mammals and
Drosophila, the detection of NaCl induces two different behaviors: low-salt
concentrations provide an attractive stimulus, whereas high-salt concentrations
are avoided. We identified the gene called serrano (sano) as being expressed in
the sensory organs of Drosophila larvae. A transgenic reporter line showed that
sano was coexpressed with Gr66a in a subset of gustatory neurons in the terminal
organ of third-instar larvae. The disruption of sano gene expression in gustatory
neurons led to the specific loss of high-salt concentration avoidance in larvae,
whereas the detection of other attractive or aversive substances was unaffected.
Moreover, using a cellular marker sensitive to calcium levels, Sano function was
shown to be required for neuronal activity in response to high-salt
concentrations. In these neurons, the loss of the DEG/ENaC channel PPK19 function
also eliminated the cellular response to high-salt concentrations. Our study
revealed that PPK19 and Sano are required in the neurons of the larval gustatory
organs for the detection of high-salt concentrations.
PMID- 25122891
TI - NMDA spike/plateau potentials in dendrites of thalamocortical neurons.
AB - Dendritic NMDA spike/plateau potentials, first discovered in cortical pyramidal
neurons, provide supralinear integration of synaptic inputs on thin and distal
dendrites, thereby increasing the impact of these inputs on the soma. The more
specific functional role of these potentials has been difficult to clarify,
partly due to the complex circuitry of cortical neurons. Thalamocortical (TC)
neurons in the dorsal lateral geniculate nucleus participate in simpler circuits.
They receive their primary afferent input from retina and send their output to
visual cortex. Cortex, in turn, regulates this output through massive feedback to
distal dendrites of the TC neurons. The TC neurons can operate in two modes
related to behavioral states: burst mode prevailing during sleep, when T-type
calcium bursts largely disrupt the transfer of signals from retina to cortex, and
tonic mode, which provides reliable transfer of retinal signals to cortex during
wakefulness. We studied dendritic potentials in TC neurons with combined two
photon calcium imaging and whole-cell recording of responses to local dendritic
glutamate iontophoresis in acute brain slices from mice. We found that NMDA
spike/plateaus can be elicited locally at distal dendrites of TC neurons. We
suggest that these dendritic potentials have important functions in the cortical
regulation of thalamocortical transmission. NMDA spike/plateaus can induce shifts
in the functional mode from burst to tonic by blockade of T-type calcium
conductances. Moreover, in tonic mode, they can facilitate the transfer of
retinal signals to cortex by depolarization of TC neurons.
PMID- 25122892
TI - Human and monkey striatal interneurons are derived from the medial ganglionic
eminence but not from the adult subventricular zone.
AB - In adult rodent and monkey brains, newly born neurons in the subventricular zone
(SVZ) in the wall of the lateral ventricle migrate into the olfactory bulb (OB)
via the rostral migratory stream (RMS). A recent study reported that interneurons
are constantly generating in the adult human striatum from the SVZ. In contrast,
by taking advantage of the continuous expression of Sp8 from the neuroblast stage
through differentiation into mature interneurons, we found that the adult human
SVZ does not generate new interneurons for the striatum. In the adult human SVZ
and RMS, very few neuroblasts were observed, and most of them expressed the
transcription factor Sp8. Neuroblasts in the adult rhesus monkey SVZ-RMS-OB
pathway also expressed Sp8. In addition, we observed that Sp8 was expressed by
most adult human and monkey OB interneurons. However, very few Sp8+ cells were in
the adult human striatum. This suggests that neuroblasts in the adult human SVZ
and RMS are likely destined for the OB, but not for the striatum. BrdU-labeling
results also revealed few if any newly born neurons in the adult rhesus monkey
striatum. Finally, on the basis of transcription factor expression, we provide
strong evidence that the vast majority of interneurons in the human and monkey
striatum are generated from the medial ganglionic eminence during embryonic
developmental stages, as they are in rodents. We conclude that, although a small
number of neuroblasts exist in the adult human SVZ, they do not migrate into the
striatum and become mature striatal interneurons.
PMID- 25122894
TI - Size and synchronization of auditory cortex promotes musical, literacy, and
attentional skills in children.
AB - Playing a musical instrument is associated with numerous neural processes that
continuously modify the human brain and may facilitate characteristic auditory
skills. In a longitudinal study, we investigated the auditory and neural
plasticity of musical learning in 111 young children (aged 7-9 y) as a function
of the intensity of instrumental practice and musical aptitude. Because of the
frequent co-occurrence of central auditory processing disorders and attentional
deficits, we also tested 21 children with attention deficit (hyperactivity)
disorder [AD(H)D]. Magnetic resonance imaging and magnetoencephalography revealed
enlarged Heschl's gyri and enhanced right-left hemispheric synchronization of the
primary evoked response (P1) to harmonic complex sounds in children who spent
more time practicing a musical instrument. The anatomical characteristics were
positively correlated with frequency discrimination, reading, and spelling
skills. Conversely, AD(H)D children showed reduced volumes of Heschl's gyri and
enhanced volumes of the plana temporalia that were associated with a distinct
bilateral P1 asynchrony. This may indicate a risk for central auditory processing
disorders that are often associated with attentional and literacy problems. The
longitudinal comparisons revealed a very high stability of auditory cortex
morphology and gray matter volumes, suggesting that the combined anatomical and
functional parameters are neural markers of musicality and attention deficits.
Educational and clinical implications are considered.
PMID- 25122893
TI - Ribosome profiling reveals a cell-type-specific translational landscape in brain
tumors.
AB - Glioma growth is driven by signaling that ultimately regulates protein synthesis.
Gliomas are also complex at the cellular level and involve multiple cell types,
including transformed and reactive cells in the brain tumor microenvironment. The
distinct functions of the various cell types likely lead to different
requirements and regulatory paradigms for protein synthesis. Proneural gliomas
can arise from transformation of glial progenitors that are driven to proliferate
via mitogenic signaling that affects translation. To investigate translational
regulation in this system, we developed a RiboTag glioma mouse model that enables
cell-type-specific, genome-wide ribosome profiling of tumor tissue. Infecting
glial progenitors with Cre-recombinant retrovirus simultaneously activates
expression of tagged ribosomes and delivers a tumor-initiating mutation.
Remarkably, we find that although genes specific to transformed cells are highly
translated, their translation efficiencies are low compared with normal brain.
Ribosome positioning reveals sequence-dependent regulation of ribosomal activity
in 5'-leaders upstream of annotated start codons, leading to differential
translation in glioma compared with normal brain. Additionally, although
transformed cells express a proneural signature, untransformed tumor-associated
cells, including reactive astrocytes and microglia, express a mesenchymal
signature. Finally, we observe the same phenomena in human disease by combining
ribosome profiling of human proneural tumor and non-neoplastic brain tissue with
computational deconvolution to assess cell-type-specific translational
regulation.
PMID- 25122895
TI - VGluT1+ neuronal glutamatergic signaling regulates postnatal developmental
maturation of cortical protoplasmic astroglia.
AB - Functional maturation of astroglia is characterized by the development of a
unique, ramified morphology and the induction of important functional proteins,
such as glutamate transporter GLT1. Although pathways regulating the early fate
specification of astroglia have been characterized, mechanisms regulating
postnatal maturation of astroglia remain essentially unknown. Here we used a new
in vivo approach to illustrate and quantitatively analyze developmental
arborization of astroglial processes. Our analysis found a particularly high
increase in the number of VGluT1(+) neuronal glutamatergic synapses that are
ensheathed by processes from individual developing astroglia from postnatal day
(P) 14 to P26, when astroglia undergo dramatic postnatal maturation. Subsequent
silencing of VGluT1(+) synaptic activity in VGluT1 KO mice significantly reduces
astroglial domain growth and the induction of GLT1 in the cortex, but has no
effect on astroglia in the hypothalamus, where non-VGluT1(+) synaptic signaling
predominates. In particular, electron microscopy analysis showed that the loss of
VGluT1(+) synaptic signaling significantly decreases perisynaptic enshealthing of
astroglial processes on synapses. To further determine whether synaptically
released glutamate mediates VGluT1(+) synaptic signaling, we pharmacologically
inhibited and genetically ablated metabotropic glutamate receptors (mGluRs,
especially mGluR5) in developing cortical astroglia and found that developmental
arborization of astroglial processes and expression of functional proteins, such
as GLT1, is significantly decreased. In summary, our genetic analysis provides
new in vivo evidence that VGluT1(+) glutamatergic signaling, mediated by the
astroglial mGluR5 receptor, regulates the functional maturation of cortical
astroglia during development. These results elucidate a new mechanism for
regulating the developmental formation of functional neuron-glia synaptic units.
PMID- 25122896
TI - A single-system model predicts recognition memory and repetition priming in
amnesia.
AB - We challenge the claim that there are distinct neural systems for explicit and
implicit memory by demonstrating that a formal single-system model predicts the
pattern of recognition memory (explicit) and repetition priming (implicit) in
amnesia. In the current investigation, human participants with amnesia
categorized pictures of objects at study and then, at test, identified fragmented
versions of studied (old) and nonstudied (new) objects (providing a measure of
priming), and made a recognition memory judgment (old vs new) for each object.
Numerous results in the amnesic patients were predicted in advance by the single
system model, as follows: (1) deficits in recognition memory and priming were
evident relative to a control group; (2) items judged as old were identified at
greater levels of fragmentation than items judged new, regardless of whether the
items were actually old or new; and (3) the magnitude of the priming effect (the
identification advantage for old vs new items) overall was greater than that of
items judged new. Model evidence measures also favored the single-system model
over two formal multiple-systems models. The findings support the single-system
model, which explains the pattern of recognition and priming in amnesia primarily
as a reduction in the strength of a single dimension of memory strength, rather
than a selective explicit memory system deficit.
PMID- 25122897
TI - Neurovascular coupling and decoupling in the cortex during voluntary locomotion.
AB - Hemodynamic signals are widely used to infer neural activity in the brain. We
tested the hypothesis that hemodynamic signals faithfully report neural activity
during voluntary behaviors by measuring cerebral blood volume (CBV) and neural
activity in the somatosensory cortex and frontal cortex of head-fixed mice during
locomotion. Locomotion induced a large and robust increase in firing rate and
gamma-band (40-100 Hz) power in the local field potential in the limb
representations in somatosensory cortex, and was accompanied by increases in CBV,
demonstrating that hemodynamic signals are coupled with neural activity in this
region. However, in the frontal cortex, CBV did not change during locomotion, but
firing rate and gamma-band power both increased, indicating a decoupling of
neural activity from the hemodynamic signal. These results show that hemodynamic
signals are not faithful indicators of the mean neural activity in the frontal
cortex during locomotion; thus, the results from fMRI and other hemodynamic
imaging methodologies for studying neural processes must be interpreted with
caution.
PMID- 25122898
TI - Chemogenetic silencing of neurons in retrosplenial cortex disrupts sensory
preconditioning.
AB - An essential aspect of episodic memory is the formation of associations between
neutral sensory cues in the environment. In light of recent evidence that this
critical aspect of learning does not require the hippocampus, we tested the
involvement of the retrosplenial cortex (RSC) in this process using a
chemogenetic approach that allowed us to temporarily silence neurons along the
entire rostrocaudal extent of the RSC. A viral vector containing the gene for a
synthetic inhibitory G-protein-coupled receptor (hM4Di) was infused into RSC.
When the receptor was later activated by systemic injection of clozapine-N-oxide,
neural activity in RSC was transiently silenced (confirmed using a patch-clamp
procedure). Rats expressing hM4Di and control rats were trained in a sensory
preconditioning procedure in which a tone and light were paired on some trials
and a white noise stimulus was presented alone on the other trials during the
Preconditioning phase. Thus, rats were given the opportunity to form an
association between a tone and a light in the absence of reinforcement. Later,
the light was paired with food. During the test phase when the auditory cues were
presented alone, controls exhibited more conditioned responding during
presentation of the tone compared with the white noise reflecting the prior
formation of a tone-light association. Silencing RSC neurons during the
Preconditioning phase prevented the formation of an association between the tone
and light and eliminated the sensory preconditioning effect. These findings
indicate that RSC may contribute to episodic memory formation by linking
essential sensory stimuli during learning.
PMID- 25122900
TI - Differential contribution of hippocampal subfields to components of associative
taste learning.
AB - The ability to associate the consumption of a taste with its positive or negative
consequences is fundamental to survival and influences the behavior of species
ranging from invertebrate to human. As a result, for both research and clinical
reasons, there has been a great effort to understand the neuronal circuits, as
well as the cellular and molecular mechanisms, underlying taste learning. From a
neuroanatomical perspective, the contributions of the cortex and amygdala are
well documented; however, the literature is riddled with conflicting results
regarding the role of the hippocampus in different facets of taste learning.
Here, we use conditional genetics in mice to block NMDA receptor-dependent
plasticity individually in each of the three major hippocampal subfields, CA1,
CA3, and the dentate gyrus, via deletion of the NR1 subunit. Across the CA1, CA3,
and dentate gyrus NR1 knock-out lines, we uncover a pattern of differential
deficits that establish the dispensability of hippocampal plasticity in
incidental taste learning, the requirement of CA1 plasticity for associative
taste learning, and a specific requirement for plasticity in the dentate gyrus
when there is a long temporal gap between the taste and its outcome. Together,
these data establish that the hippocampus is involved in associative taste
learning and suggest an episodic component to this type of memory.
PMID- 25122899
TI - Spinal cord injury causes brain inflammation associated with cognitive and
affective changes: role of cell cycle pathways.
AB - Experimental spinal cord injury (SCI) causes chronic neuropathic pain associated
with inflammatory changes in thalamic pain regulatory sites. Our recent studies
examining chronic pain mechanisms after rodent SCI showed chronic inflammatory
changes not only in thalamus, but also in other regions including hippocampus and
cerebral cortex. Because changes appeared similar to those in our rodent TBI
models that are associated with neurodegeneration and neurobehavioral
dysfunction, we examined effects of mouse SCI on cognition, depressive-like
behavior, and brain inflammation. SCI caused spatial and retention memory
impairment and depressive-like behavior, as evidenced by poor performance in the
Morris water maze, Y-maze, novel objective recognition, step-down passive
avoidance, tail suspension, and sucrose preference tests. SCI caused chronic
microglial activation in the hippocampus and cerebral cortex, where microglia
with hypertrophic morphologies and M1 phenotype predominated. Stereological
analyses showed significant neuronal loss in the hippocampus at 12 weeks but not
8 d after injury. Increased cell-cycle-related gene (cyclins A1, A2, D1, E2F1,
and PCNA) and protein (cyclin D1 and CDK4) expression were found chronically in
hippocampus and cerebral cortex. Systemic administration of the selective cyclin
dependent kinase inhibitor CR8 after SCI significantly reduced cell cycle gene
and protein expression, microglial activation and neurodegeneration in the brain,
cognitive decline, and depression. These studies indicate that SCI can initiate a
chronic brain neurodegenerative response, likely related to delayed, sustained
induction of M1-type microglia and related cell cycle activation, which result in
cognitive deficits and physiological depression.
PMID- 25122902
TI - Interplay between synchronization of multivesicular release and recruitment of
additional release sites support short-term facilitation at hippocampal mossy
fiber to CA3 pyramidal cells synapses.
AB - Synaptic short-term plasticity is a key regulator of neuronal communication and
is controlled via various mechanisms. A well established property of mossy fiber
to CA3 pyramidal cell synapses is the extensive short-term facilitation during
high-frequency bursts. We investigated the mechanisms governing facilitation
using a combination of whole-cell electrophysiological recordings, electrical
minimal stimulation, and random-access two-photon microscopy in acute mouse
hippocampal slices. Two distinct presynaptic mechanisms were involved in short
term facilitation, with their relative contribution dependent on extracellular
calcium concentration. The synchronization of multivesicular release was observed
during trains of facilitating EPSCs recorded in 1.2 mM external Ca(2+)
([Ca(2+)]e). Indeed, covariance analysis revealed a gradual augmentation in
quantal size during trains of EPSCs, and application of the low-affinity
glutamate receptor antagonist gamma-D-glutamylglycine showed an increase in cleft
glutamate concentration during paired-pulse stimulation. Whereas synchronization
of multivesicular release contributed to the facilitation in 1.2 mM [Ca(2+)]e,
variance-mean analysis showed that recruitment of more release sites (N) was
likely to account for the larger facilitation observed in 2.5 mM [Ca(2+)]e.
Furthermore, this increase in N could be promoted by calcium microdomains of
heterogeneous amplitudes observed in single mossy fiber boutons. Our findings
suggest that the combination of multivesicular release and the recruitment of
additional release sites act together to increase glutamate release during burst
activity. This is supported by the compartmentalized spatial profile of calcium
elevations in boutons and helps to expand the dynamic range of mossy fibers
information transfer.
PMID- 25122901
TI - The essential role of primate orbitofrontal cortex in conflict-induced executive
control adjustment.
AB - Conflict in information processing evokes trial-by-trial behavioral modulations.
Influential models suggest that adaptive tuning of executive control, mediated by
mid-dorsal lateral prefrontal cortex (mdlPFC) and anterior cingulate cortex
(ACC), underlies these modulations. However, mdlPFC and ACC are parts of
distributed brain networks including orbitofrontal cortex (OFC), posterior
cingulate cortex (PCC), and superior-dorsal lateral prefrontal cortex (sdlPFC).
Contributions of these latter areas in adaptive tuning of executive control are
unknown. We trained monkeys to perform a matching task in which they had to
resolve the conflict between two behavior-guiding rules. Here, we report that
bilateral lesions in OFC, but not in PCC or sdlPFC, impaired selection between
these competing rules. In addition, the behavioral adaptation that is normally
induced by experiencing conflict disappeared in OFC-lesioned, but remained normal
in PCC-lesioned or sdlPFC-lesioned monkeys. Exploring underlying neuronal
processes, we found that the activity of neurons in OFC represented the conflict
between behavioral options independent from the other aspects of the task.
Responses of OFC neurons to rewards also conveyed information of the conflict
level that the monkey had experienced along the course to obtain the reward. Our
findings indicate dissociable functions for five closely interconnected cortical
areas suggesting that OFC and mdlPFC, but not PCC or sdlPFC or ACC, play
indispensable roles in conflict-dependent executive control of on-going behavior.
Both mdlPFC and OFC support detection of conflict and its integration with the
task goal, but in contrast to mdlPFC, OFC does not retain the necessary
information for conflict-induced modulation of future decisions.
PMID- 25122904
TI - Dynamic target match signals in perirhinal cortex can be explained by
instantaneous computations that act on dynamic input from inferotemporal cortex.
AB - Finding sought objects requires the brain to combine visual and target signals to
determine when a target is in view. To investigate how the brain implements these
computations, we recorded neural responses in inferotemporal cortex (IT) and
perirhinal cortex (PRH) as macaque monkeys performed a delayed-match-to-sample
target search task. Our data suggest that visual and target signals were combined
within or before IT in the ventral visual pathway and then passed onto PRH, where
they were reformatted into a more explicit target match signal over ~10-15 ms.
Accounting for these dynamics in PRH did not require proposing dynamic
computations within PRH itself but, rather, could be attributed to instantaneous
PRH computations performed upon an input representation from IT that changed with
time. We found that the dynamics of the IT representation arose from two commonly
observed features: individual IT neurons whose response preferences were not
simply rescaled with time and variable response latencies across the population.
Our results demonstrate that these types of time-varying responses have important
consequences for downstream computation and suggest that dynamic representations
can arise within a feedforward framework as a consequence of instantaneous
computations performed upon time-varying inputs.
PMID- 25122906
TI - Post-error slowing as a consequence of disturbed low-frequency oscillatory phase
entrainment.
AB - A common finding across many reaction time tasks is that people slow down on
trials following errors, a phenomenon known as post-error slowing. In the present
study, we tested a novel hypothesis about the neural mechanism underlying post
error slowing. Recent research has shown that when task-relevant stimuli occur in
a rhythmic stream, neuronal oscillations entrain to the task structure, thereby
enhancing reaction speed. We hypothesized that under such circumstances post
error slowing results from an error-induced disturbance of this endogenous brain
rhythm. To test this hypothesis, we measured oscillatory EEG dynamics while human
subjects performed a demanding discrimination task under time pressure. We found
that low-frequency neuronal oscillations entrained to the stimulus presentation
rhythm, and that the low-frequency phase at stimulus onset predicted the speed of
responding. Importantly, we found that this entrainment was disrupted following
errors, and that the degree of phase disturbance was closely related to the
degree of post-error slowing on the subsequent trial. These results describe a
new mechanism underlying behavioral changes following errors.
PMID- 25122907
TI - Recycling endosomes undergo rapid closure of a fusion pore on exocytosis in
neuronal dendrites.
AB - Exocytosis of recycling endosomes (REs) represents the last step of receptor and
membrane recycling, a fundamental process involved in many aspects of cell
physiology. In neurons, it is involved in the control of cell polarity and
synaptic plasticity and is locally and tightly regulated. However, its molecular
mechanisms are still poorly understood. We have imaged single exocytosis events
of REs in rat hippocampal neurons in culture transfected with three types of
receptors tagged with the pH-sensitive GFP mutant superecliptic phluorin. We
found that exocytosis events are grouped into two categories: (1) short burst
events in which receptors diffuse into the plasma membrane in a few seconds; and
(2) long display events in which receptors remain visible and clustered after
exocytosis for many seconds. Display events are much rarer in non-neuronal cells,
such as fibroblasts and astrocytes. Using two-color imaging and fast
extracellular solution changes, we show that display events correspond to the
rapid opening and closing of a fusion pore (or "kiss-and-run") with a median
opening time of 2.6 s, which restricts the diffusion of multiple receptor types
and bound cargo. Moreover, the RE marker Rab11 remains enriched after display
exocytosis events and controls the mode of RE exocytosis. Finally, a given RE can
undergo multiple rounds of display exocytosis. The last step of recycling can
thus be controlled in neurons for the selective delivery of receptors at the cell
surface.
PMID- 25122903
TI - A heroin addiction severity-associated intronic single nucleotide polymorphism
modulates alternative pre-mRNA splicing of the MU opioid receptor gene OPRM1 via
hnRNPH interactions.
AB - Single nucleotide polymorphisms (SNPs) in the OPRM1 gene have been associated
with vulnerability to opioid dependence. The current study identifies an
association of an intronic SNP (rs9479757) with the severity of heroin addiction
among Han-Chinese male heroin addicts. Individual SNP analysis and haplotype
based analysis with additional SNPs in the OPRM1 locus showed that mild heroin
addiction was associated with the AG genotype, whereas severe heroin addiction
was associated with the GG genotype. In vitro studies such as electrophoretic
mobility shift assay, minigene, siRNA, and antisense morpholino oligonucleotide
studies have identified heterogeneous nuclear ribonucleoprotein H (hnRNPH) as the
major binding partner for the G-containing SNP site. The G-to-A transition
weakens hnRNPH binding and facilitates exon 2 skipping, leading to altered
expressions of OPRM1 splice-variant mRNAs and hMOR-1 proteins. Similar changes in
splicing and hMOR-1 proteins were observed in human postmortem prefrontal cortex
with the AG genotype of this SNP when compared with the GG genotype.
Interestingly, the altered splicing led to an increase in hMOR-1 protein levels
despite decreased hMOR-1 mRNA levels, which is likely contributed by a concurrent
increase in single transmembrane domain variants that have a chaperone-like
function on MOR-1 protein stability. Our studies delineate the role of this SNP
as a modifier of OPRM1 alternative splicing via hnRNPH interactions, and suggest
a functional link between an SNP-containing splicing modifier and the severity of
heroin addiction.
PMID- 25122905
TI - Characterization of transcriptomes of cochlear inner and outer hair cells.
AB - Inner hair cells (IHCs) and outer hair cells (OHCs) are the two types of sensory
receptor cells that are critical for hearing in the mammalian cochlea. IHCs and
OHCs have different morphology and function. The genetic mechanisms that define
their morphological and functional specializations are essentially unknown. The
transcriptome reflects the genes that are being actively expressed in a cell and
holds the key to understanding the molecular mechanisms of the biological
properties of the cell. Using DNA microarray, we examined the transcriptome of
2000 individually collected IHCs and OHCs from adult mouse cochleae. We show that
16,647 and 17,711 transcripts are expressed in IHCs and OHCs, respectively. Of
those genes, ~73% are known genes, 22% are uncharacterized sequences, and 5.0%
are noncoding RNAs in both populations. A total of 16,117 transcripts are
expressed in both populations. Uniquely and differentially expressed genes
account for <15% of all genes in either cell type. The top 10 differentially
expressed genes include Slc17a8, Dnajc5b, Slc1a3, Atp2a3, Osbpl6, Slc7a14, Bcl2,
Bin1, Prkd1, and Map4k4 in IHCs and Slc26a5, C1ql1, Strc, Dnm3, Plbd1, Lbh,
Olfm1, Plce1, Tectb, and Ankrd22 in OHCs. We analyzed commonly and differentially
expressed genes with the focus on genes related to hair cell specializations in
the apical, basolateral, and synaptic membranes. Eighty-three percent of the
known deafness-related genes are expressed in hair cells. We also analyzed genes
involved in cell-cycle regulation. Our dataset holds an extraordinary trove of
information about the molecular mechanisms underlying hair cell morphology,
function, pathology, and cell-cycle control.
PMID- 25122909
TI - Volitional walking via upper limb muscle-controlled stimulation of the lumbar
locomotor center in man.
AB - Gait disturbance in individuals with spinal cord lesion is attributed to the
interruption of descending pathways to the spinal locomotor center, whereas
neural circuits below and above the lesion maintain their functional capability.
An artificial neural connection (ANC), which bridges supraspinal centers and
locomotor networks in the lumbar spinal cord beyond the lesion site, may restore
the functional impairment. To achieve an ANC that sends descending voluntary
commands to the lumbar locomotor center and bypasses the thoracic spinal cord,
upper limb muscle activity was converted to magnetic stimuli delivered
noninvasively over the lumbar vertebra. Healthy participants were able to
initiate and terminate walking-like behavior and to control the step cycle
through an ANC controlled by volitional upper limb muscle activity. The walking
like behavior stopped just after the ANC was disconnected from the participants
even when the participant continued to swing arms. Furthermore, additional
simultaneous peripheral electrical stimulation to the foot via the ANC enhanced
this walking-like behavior. Kinematics of the induced behaviors were identical to
those observed in voluntary walking. These results demonstrate that the ANC
induces volitionally controlled, walking-like behavior of the legs. This paradigm
may be able to compensate for the dysfunction of descending pathways by sending
commands to the preserved locomotor center at the lumbar spinal cord and may
enable individuals with paraplegia to regain volitionally controlled walking.
PMID- 25122910
TI - Perceptual gloss parameters are encoded by population responses in the monkey
inferior temporal cortex.
AB - There are neurons localized in the lower bank of the superior temporal sulcus
(STS) in the inferior temporal (IT) cortex of the monkey that selectively respond
to specific ranges of gloss characterized by combinations of three physical
reflectance parameters: specular reflectance (rhos), diffuse reflectance (rhod),
and spread of specular reflection (alpha; Nishio et al., 2012). In the present
study, we examined how the activities of these gloss-selective IT neurons are
related to perceived gloss. In an earlier psychophysical study, Ferwerda et al.
(2001) identified a perceptually uniform gloss space defined by two axes where
the c-axis corresponds to a nonlinear combination of rhos and rhod and the d-axis
corresponds to 1 - alpha. In the present study, we tested the responses of gloss
selective neurons to stimuli in the perceptual gloss space defined by the c- and
d-axes. We found that gloss-selective neurons systematically changed their
responses in the perceptual gloss space, and the distribution of the tuning
directions of the population of gloss-selective neurons is biased toward
directions in which perceived gloss increases. We also found that a set of
perceptual gloss parameters as well as surface albedo can be well explained by
the population activities of gloss-selective neurons, and that these parameters
are likely encoded by the gloss-selective neurons in this area of the STS to
represent various glosses. These results thus provide evidence that the IT cortex
represents perceptual gloss space.
PMID- 25122908
TI - Multisensory training improves auditory spatial processing following bilateral
cochlear implantation.
AB - Cochlear implants (CIs) partially restore hearing to the deaf by directly
stimulating the inner ear. In individuals fitted with CIs, lack of auditory
experience due to loss of hearing before language acquisition can adversely
impact outcomes. For example, adults with early-onset hearing loss generally do
not integrate inputs from both ears effectively when fitted with bilateral CIs
(BiCIs). Here, we used an animal model to investigate the effects of long-term
deafness on auditory localization with BiCIs and approaches for promoting the use
of binaural spatial cues. Ferrets were deafened either at the age of hearing
onset or as adults. All animals were implanted in adulthood, either unilaterally
or bilaterally, and were subsequently assessed for their ability to localize
sound in the horizontal plane. The unilaterally implanted animals were unable to
perform this task, regardless of the duration of deafness. Among animals with
BiCIs, early-onset hearing loss was associated with poor auditory localization
performance, compared with late-onset hearing loss. However, performance in the
early-deafened group with BiCIs improved significantly after multisensory
training with interleaved auditory and visual stimuli. We demonstrate a possible
neural substrate for this by showing a training-induced improvement in the
responsiveness of auditory cortical neurons and in their sensitivity to
interaural level differences, the principal localization cue available to BiCI
users. Importantly, our behavioral and physiological evidence demonstrates a
facilitative role for vision in restoring auditory spatial processing following
potential cross-modal reorganization. These findings support investigation of a
similar training paradigm in human CI users.
PMID- 25122911
TI - Microsaccadic responses indicate fast categorization of sounds: a novel approach
to study auditory cognition.
AB - The mental chronometry of the human brain's processing of sounds to be
categorized as targets has intensively been studied in cognitive neuroscience.
According to current theories, a series of successive stages consisting of the
registration, identification, and categorization of the sound has to be completed
before participants are able to report the sound as a target by button press
after ~300-500 ms. Here we use miniature eye movements as a tool to study the
categorization of a sound as a target or nontarget, indicating that an initial
categorization is present already after 80-100 ms. During visual fixation, the
rate of microsaccades, the fastest components of miniature eye movements, is
transiently modulated after auditory stimulation. In two experiments, we measured
microsaccade rates in human participants in an auditory three-tone oddball
paradigm (including rare nontarget sounds) and observed a difference in the
microsaccade rates between targets and nontargets as early as 142 ms after sound
onset. This finding was replicated in a third experiment with directed saccades
measured in a paradigm in which tones had to be matched to score-like visual
symbols. Considering the delays introduced by (motor) signal transmission and
data analysis constraints, the brain must have differentiated target from
nontarget sounds as fast as 80-100 ms after sound onset in both paradigms. We
suggest that predictive information processing for expected input makes higher
cognitive attributes, such as a sound's identity and category, available already
during early sensory processing. The measurement of eye movements is thus a
promising approach to investigate hearing.
PMID- 25122912
TI - Amyloid precursor protein dimerization and synaptogenic function depend on copper
binding to the growth factor-like domain.
AB - Accumulating evidence suggests that the copper-binding amyloid precursor protein
(APP) has an essential synaptic function. APP synaptogenic function depends on
trans-directed dimerization of the extracellular E1 domain encompassing a growth
factor-like domain (GFLD) and a copper-binding domain (CuBD). Here we report the
1.75 A crystal structure of the GFLD in complex with a copper ion bound with high
affinity to an extended hairpin loop at the dimerization interface. In
coimmunoprecipitation assays copper binding promotes APP interaction, whereas
mutations in the copper-binding sites of either the GFLD or CuBD result in a
drastic reduction in APP cis-orientated dimerization. We show that copper is
essential and sufficient to induce trans-directed dimerization of purified APP.
Furthermore, a mixed culture assay of primary neurons with HEK293 cells
expressing different APP mutants revealed that APP potently promotes
synaptogenesis depending on copper binding to the GFLD. Together, these findings
demonstrate that copper binding to the GFLD of APP is required for APP cis-/trans
directed dimerization and APP synaptogenic function. Thus, neuronal activity or
disease-associated changes in copper homeostasis likely go along with altered APP
synaptic function.
PMID- 25122913
TI - Escaping compound eye ancestry: the evolution of single-chamber eyes in
holometabolous larvae.
AB - Stemmata, the eyes of holometabolous insect larvae, have gained little attention,
even though they exhibit remarkably different optical solutions, ranging from
compound eyes with upright images, to sophisticated single-chamber eyes with
inverted images. Such optical differences raise the question of how major
transitions may have occurred. Stemmata evolved from compound eye ancestry, and
optical differences are apparent even in some of the simplest systems that share
strong cellular homology with adult ommatidia. The transition to sophisticated
single-chamber eyes occurred many times independently, and in at least two
different ways: through the fusion of many ommatidia [as in the sawfly
(Hymenoptera)], and through the expansion of single ommatidia [as in tiger
beetles (Coleoptera), antlions (Neuroptera) and dobsonflies (Megaloptera)].
Although ommatidia-like units frequently have multiple photoreceptor layers
(tiers), sophisticated image-forming stemmata tend to only have one photoreceptor
tier, presumably a consequence of the lens only being able to efficiently focus
light on to one photoreceptor layer. An interesting exception is found in some
diving beetles [Dytiscidae (Coleoptera)], in which two retinas receive sharp
images from a bifocal lens. Taken together, stemmata represent a great model
system to study an impressive set of optical solutions that evolved from a
relatively simple ancestral organization.
PMID- 25122914
TI - The role of titin in eccentric muscle contraction.
AB - Muscle contraction and force regulation in skeletal muscle have been thought to
occur exclusively through the relative sliding of and the interaction between the
contractile filaments actin and myosin. While this two-filament sarcomere model
has worked well in explaining the properties of isometrically and concentrically
contracting muscle, it has failed miserably in explaining experimental
observations in eccentric contractions. Here, I suggest, and provide evidence,
that a third filament, titin, is involved in force regulation of sarcomeres by
adjusting its stiffness in an activation-dependent (calcium) and active force
dependent manner. Upon muscle activation, titin binds calcium at specific sites,
thereby increasing its stiffness, and cross-bridge attachment to actin is thought
to free up binding sites for titin on actin, thereby reducing titin's free-spring
length, thus increasing its stiffness and force upon stretch of active muscle.
This role of titin as a third force regulating myofilament in sarcomeres,
although not fully proven, would account for many of the unexplained properties
of eccentric muscle contraction, while simultaneously not affecting the
properties predicted by the two-filament cross-bridge model in isometric and
concentric muscle function. Here, I identify the problems of the two-filament
sarcomere model and demonstrate the advantages of the three-filament model by
providing evidence of titin's contribution to active force in eccentric muscle
function.
PMID- 25122916
TI - Feeding rates and under-ice foraging strategies of the smallest lunge filter
feeder, the Antarctic minke whale (Balaenoptera bonaerensis).
AB - Body size and feeding mode are two fundamental characteristics that determine
foraging performance and ecological niche. As the smallest obligate lunge filter
feeders, minke whales represent an ideal system for studying the physical and
energetic limits of filter feeding in endotherms. We used multi-sensor suction
cup tags to quantify the feeding performance of Antarctic minke whales. Foraging
dives around and beneath sea ice contained up to 24 lunges per dive, the highest
feeding rates for any lunge-feeding whale. Their small size allows minke whales
access to krill in sea-ice environments not easily accessible to larger baleen
whales. Furthermore, their ability to filter feed provides an advantage over
other smaller sympatric krill predators such as penguins and seals that feed on
individual prey. The unique combination of body size, feeding mechanism and sea
ice habitat of Antarctic minke whales defines a previously undocumented energetic
niche that is unique among aquatic vertebrates.
PMID- 25122915
TI - Temporal binding of neural responses for focused attention in biosonar.
AB - Big brown bats emit biosonar sounds and perceive their surroundings from the
delays of echoes received by the ears. Broadcasts are frequency modulated (FM)
and contain two prominent harmonics sweeping from 50 to 25 kHz (FM1) and from 100
to 50 kHz (FM2). Individual frequencies in each broadcast and each echo evoke
single-spike auditory responses. Echo delay is encoded by the time elapsed
between volleys of responses to broadcasts and volleys of responses to echoes. If
echoes have the same spectrum as broadcasts, the volley of neural responses to
FM1 and FM2 is internally synchronized for each sound, which leads to sharply
focused delay images. Because of amplitude-latency trading, disruption of
response synchrony within the volleys occurs if the echoes are lowpass filtered,
leading to blurred, defocused delay images. This effect is consistent with the
temporal binding hypothesis for perceptual image formation. Bats perform
inexplicably well in cluttered surroundings where echoes from off-side objects
ought to cause masking. Off-side echoes are lowpass filtered because of the shape
of the broadcast beam, and they evoke desynchronized auditory responses. The
resulting defocused images of clutter do not mask perception of focused images
for targets. Neural response synchronization may select a target to be the focus
of attention, while desynchronization may impose inattention on the surroundings
by defocusing perception of clutter. The formation of focused biosonar images
from synchronized neural responses, and the defocusing that occurs with
disruption of synchrony, quantitatively demonstrates how temporal binding may
control attention and bring a perceptual object into existence.
PMID- 25122917
TI - Pre-start timing information is used to set final linear speed in a C-start
manoeuvre.
AB - In their unique hunting behaviour, archerfish use a complex motor decision to
secure their prey: based solely on how dislodged prey initially falls, they
select an adapted C-start manoeuvre that turns the fish right towards the point
on the water surface where their prey will later land. Furthermore, they take off
at a speed that is set so as to arrive in time. We show here that the C-start
manoeuvre and not subsequent tail beating is necessary and sufficient for setting
this adaptive level of speed. Furthermore, the C-start pattern is adjusted to
independently determine both the turning angle and the take-off speed. The
selection of both aspects requires no a priori information and is done based on
information sampled from the onset of target motion until the C-start is
launched. Fin strokes can occur right after the C-start manoeuvre but are not
required to fine-tune take-off speed, but rather to maintain it. By probing the
way in which the fish set their take-off speed in a wide range of conditions in
which distance from the later catching point and time until impact varied widely
and unpredictably, we found that the C-start manoeuvre is programmed based on pre
C-start estimates of distance and time until impact. Our study hence provides the
first evidence for a C-start that is fine-tuned to produce an adaptive speed
level.
PMID- 25122918
TI - Adaptive changes in echolocation sounds by Pipistrellus abramus in response to
artificial jamming sounds.
AB - The echolocation behavior of Pipistrellus abramus during exposure to artificial
jamming sounds during flight was investigated. Echolocation pulses emitted by the
bats were recorded using a telemetry microphone mounted on the bats' backs, and
their adaptation based on acoustic characteristics of emitted pulses was assessed
in terms of jamming-avoidance responses (JARs). In experiment 1, frequency
modulated jamming sounds (3 ms duration) mimicking echolocation pulses of P.
abramus were prepared. All bats showed significant increases in the terminal
frequency of the frequency-modulated pulse by an average of 2.1-4.5 kHz when the
terminal frequency of the jamming sounds was lower than the bats' own pulses.
This frequency shift was not observed using jamming frequencies that overlapped
with or were higher than the bats' own pulses. These findings suggest that JARs
in P. abramus are sensitive to the terminal frequency of jamming pulses and that
the bats' response pattern was dependent on the slight difference in stimulus
frequency. In experiment 2, when bats were repeatedly exposed to a band-limited
noise of 70 ms duration, the bats in flight more frequently emitted pulses during
silent periods between jamming sounds, suggesting that the bats could actively
change the timing of pulse emissions, even during flight, to avoid temporal
overlap with jamming sounds. Our findings demonstrate that bats could adjust
their vocalized frequency and emission timing during flight in response to
acoustic jamming stimuli.
PMID- 25122919
TI - Forward shift of feeding buzz components of dolphins and belugas during
associative learning reveals a likely connection to reward expectation, pleasure
and brain dopamine activation.
AB - For many years, we heard sounds associated with reward from dolphins and belugas.
We named these pulsed sounds victory squeals (VS), as they remind us of a child's
squeal of delight. Here we put these sounds in context with natural and learned
behavior. Like bats, echolocating cetaceans produce feeding buzzes as they
approach and catch prey. Unlike bats, cetaceans continue their feeding buzzes
after prey capture and the after portion is what we call the VS. Prior to
training (or conditioning), the VS comes after the fish reward; with repeated
trials it moves to before the reward. During training, we use a whistle or other
sound to signal a correct response by the animal. This sound signal, named a
secondary reinforcer (SR), leads to the primary reinforcer, fish. Trainers
usually name their whistle or other SR a bridge, as it bridges the time gap
between the correct response and reward delivery. During learning, the SR becomes
associated with reward and the VS comes after the SR rather than after the fish.
By following the SR, the VS confirms that the animal expects a reward. Results of
early brain stimulation work suggest to us that SR stimulates brain dopamine
release, which leads to the VS. Although there are no direct studies of dopamine
release in cetaceans, we found that the timing of our VS is consistent with a
response after dopamine release. We compared trained vocal responses to auditory
stimuli with VS responses to SR sounds. Auditory stimuli that did not signal
reward resulted in faster responses by a mean of 151 ms for dolphins and 250 ms
for belugas. In laboratory animals, there is a 100 to 200 ms delay for dopamine
release. VS delay in our animals is similar and consistent with vocalization
after dopamine release. Our novel observation suggests that the dopamine reward
system is active in cetacean brains.
PMID- 25122921
TI - Genetic evidence for monogamy in the dwarf seahorse, Hippocampus zosterae.
AB - Syngnathid fishes (pipefishes, seahorses, and seadragons) exhibit a wide array of
mating systems ranging from monogamy with long-term pair bonds to more
promiscuous mating systems, such as polyandry and polygynandry. Some seahorses,
including the dwarf seahorse Hippocampus zosterae, have been found to be socially
monogamous. Although several seahorse species have also been shown to be
genetically monogamous, parentage analysis has not yet been applied to the dwarf
seahorse. We developed 8 novel microsatellites for the dwarf seahorse to conduct
genetic parentage analysis to confirm that this species is indeed monogamous.
Using 4 selected loci and a total of 16 pregnant male seahorses, with 8 collected
in Florida and 8 sampled in Texas, we genotyped all of the offspring within each
male's brood to determine the maternal contributions to each brood. We found a
maximum of 4 alleles per locus segregating within each pregnant male's brood, a
pattern consistent with each brood having exactly 1 mother and 1 father. These
results support previous laboratory-based behavioral studies and indicate that
the dwarf seahorse, H. zosterae, is genetically monogamous.
PMID- 25122923
TI - Secretion and immunogenicity of the meningioma-associated antigen TXNDC16.
AB - In a previous study, we identified thioredoxin domain containing 16 (TXNDC16) as
a meningioma-associated Ag by protein macroarray screening. Serological screening
detected autoantibodies against TXNDC16 exclusively in meningioma patients' sera
and not in sera of healthy controls. TXNDC16 was previously found to be an
endoplasmic reticulum (ER)-luminal glycoprotein. In this study, we show an
additional ER-associated localization of TXNDC16 in the cytosol by in vitro
synthesis, molecular mass shift assay, and flow cytometry. We were able to show
TXNDC16 secretion in different human cell lines due to masked and therefore
nonfunctional ER retrieval motif. A previously indicated exosomal TXNDC16
secretion could not be confirmed in HEK293 cells. The secreted serum protein
TXNDC16 is bound in circulating immune complexes, which were found both in
meningioma and healthy blood donor sera. Employing a customized array with 163
overlapping TXNDC16 peptides and measuring autoantibody reactivity, we achieved
discrimination of meningioma sera from healthy controls with an accuracy of 87.2%
using a set of only five immunogenic TXNDC16 epitopes.
PMID- 25122924
TI - Antibody-mediated immune suppression of erythrocyte alloimmunization can occur
independently from red cell clearance or epitope masking in a murine model.
AB - Anti-D can prevent immunization to the RhD Ag on RBCs, a phenomenon commonly
termed Ab-mediated immune suppression (AMIS). The most accepted theory to explain
this effect has been the rapid clearance of RBCs. In mouse models using SRBC,
these xenogeneic cells are always rapidly cleared even without Ab, and
involvement of epitope masking of the SRBC Ags by the AMIS-inducing Ab (anti
SRBC) has been suggested. To address these hypotheses, we immunized mice with
murine transgenic RBCs expressing the HOD Ag (hen egg lysozyme [HEL], in sequence
with ovalbumin, and the human Duffy transmembrane protein) in the presence of
polyclonal Abs or mAbs to the HOD molecule. The isotype, specificity, and ability
to induce AMIS of these Abs were compared with accelerated clearance as well as
steric hindrance of the HOD Ag. Mice made IgM and IgG reactive with the HEL
portion of the molecule only. All six of the mAbs could inhibit the response. The
HEL-specific Abs (4B7, IgG1; GD7, IgG2b; 2F4, IgG1) did not accelerate clearance
of the HOD-RBCs and displayed partial epitope masking. The Duffy-specific Abs
(MIMA 29, IgG2a; CBC-512, IgG1; K6, IgG1) all caused rapid clearance of HOD RBCs
without steric hindrance. To our knowledge, this is the first demonstration of
AMIS to erythrocytes in an all-murine model and shows that AMIS can occur in the
absence of RBC clearance or epitope masking. The AMIS effect was also independent
of IgG isotype and epitope specificity of the AMIS-inducing Ab.
PMID- 25122922
TI - The natural product phyllanthusmin C enhances IFN-gamma production by human NK
cells through upregulation of TLR-mediated NF-kappaB signaling.
AB - Natural products are a major source for cancer drug development. NK cells are a
critical component of innate immunity with the capacity to destroy cancer cells,
cancer-initiating cells, and clear viral infections. However, few reports
describe a natural product that stimulates NK cell IFN-gamma production and
unravel a mechanism of action. In this study, through screening, we found that a
natural product, phyllanthusmin C (PL-C), alone enhanced IFN-gamma production by
human NK cells. PL-C also synergized with IL-12, even at the low cytokine
concentration of 0.1 ng/ml, and stimulated IFN-gamma production in both human
CD56(bright) and CD56(dim) NK cell subsets. Mechanistically, TLR1 and/or TLR6
mediated PL-C's activation of the NF-kappaB p65 subunit that in turn bound to the
proximal promoter of IFNG and subsequently resulted in increased IFN-gamma
production in NK cells. However, IL-12 and IL-15Rs and their related STAT
signaling pathways were not responsible for the enhanced IFN-gamma secretion by
PL-C. PL-C induced little or no T cell IFN-gamma production or NK cell
cytotoxicity. Collectively, we identify a natural product with the capacity to
selectively enhance human NK cell IFN-gamma production. Given the role of IFN
gamma in immune surveillance, additional studies to understand the role of this
natural product in prevention of cancer or infection in select populations are
warranted.
PMID- 25122930
TI - Early events in annelid regeneration: a cellular perspective.
AB - The ability to regenerate extensive portions of the body is widespread among the
phylum Annelida and this group includes some of the most highly regenerative
animals known. Knowledge of the cellular and molecular basis of regeneration in
this group is thus important for understanding how regenerative processes have
evolved both within the group and across animal phyla. Here, the cellular basis
of annelid regeneration is reviewed, with a focus on the earliest steps of
regeneration, namely wound-healing and formation of the blastema. Information
from a wide range of annelids is compiled in order to identify common and
variable elements. There is a large body of valuable older literature on the
cellular basis of regeneration in annelids and an effort is made to review this
literature in addition to more recent studies. Annelids typically seal the wound
through muscular contraction and undergo some autolysis of tissue at the site of
the wound. Bodily injury elicits extensive cell migration toward the wound,
involving several different types of cells. Some migrating cells form a tissue
clot and phagocytize damaged tissues, whereas others are inferred to contribute
to regenerated tissue, specifically mesodermal tissue. In one annelid subgroup,
the clitellates, a group of mesodermal cells, sometimes referred to as neoblasts,
is inferred to migrate over considerable distances, with cells moving to the
wound from several segments away. Epidermis and gut epithelia severed upon
amputation typically heal by fusing with like tissue, although not always. After
amputation, cellular contacts with the extracellular matrix are disrupted and
major changes in cell morphology and adhesion occur within tissues near the
wound. Interactions of tissues at the wound appear key for initiating a blastema,
with a particularly important role suggested for the ventral nerve cord, although
species are variable in this regard; longer-distance effects mediated by the
brain are also reported. The anterior-posterior polarity of the blastema can be
mis-assigned, leading most commonly to double-headed worms, and the dorsal
ventral polarity of the blastema appears to be induced by the ventral nerve cord.
The blastema is thought to arise from contributions of all three tissue layers,
with each layer replacing itself in a tissue-specific manner. Blastemal cells
originate mostly locally, although some long-distance migration of source-cells
is suggested in clitellates. A number of important questions remain about the
cellular basis of regeneration in annelids and addressing many of these would be
greatly aided by developing approaches to identify and isolate specific cell
types and techniques to image and trace cells in vivo.
PMID- 25122925
TI - The surprising dynamics of scaffolding proteins.
AB - The function of scaffolding proteins is to bring together two or more proteins in
a relatively stable configuration, hence their name. Numerous scaffolding
proteins are found in nature, many having multiple protein-protein interaction
modules. Over the past decade, examples of scaffolding complexes long thought to
be stable have instead been found to be surprisingly dynamic. These studies are
scattered among different biological systems, and so the concept that scaffolding
complexes might not always represent stable entities and that their dynamics can
be regulated has not garnered general attention. We became aware of this issue in
our studies of a scaffolding protein in microvilli, which forced us to reevaluate
its contribution to their structure. The purpose of this Perspective is to draw
attention to this phenomenon and discuss why complexes might show regulated
dynamics. We also wish to encourage more studies on the dynamics of "stable"
complexes and to provide a word of caution about how functionally important
dynamic associations may be missed in biochemical and proteomic studies.
PMID- 25122933
TI - Don't lose sleep over seasonal affective disorder.
PMID- 25122931
TI - Urinary tract infections: what both men and women should know.
PMID- 25122928
TI - Early pregnancy prediction of preeclampsia in nulliparous women, combining
clinical risk and biomarkers: the Screening for Pregnancy Endpoints (SCOPE)
international cohort study.
AB - More than half of all cases of preeclampsia occur in healthy first-time pregnant
women. Our aim was to develop a method to predict those at risk by combining
clinical factors and measurements of biomarkers in women recruited to the
Screening for Pregnancy Endpoints (SCOPE) study of low-risk nulliparous women.
Forty-seven biomarkers identified on the basis of (1) association with
preeclampsia, (2) a biological role in placentation, or (3) a role in cellular
mechanisms involved in the pathogenesis of preeclampsia were measured in plasma
sampled at 14 to 16 weeks' gestation from 5623 women. The cohort was randomly
divided into training (n=3747) and validation (n=1876) cohorts. Preeclampsia
developed in 278 (4.9%) women, of whom 28 (0.5%) developed early-onset
preeclampsia. The final model for the prediction of preeclampsia included
placental growth factor, mean arterial pressure, and body mass index at 14 to 16
weeks' gestation, the consumption of >=3 pieces of fruit per day, and mean
uterine artery resistance index. The area under the receiver operator curve (95%
confidence interval) for this model in training and validation cohorts was 0.73
(0.70-0.77) and 0.68 (0.63-0.74), respectively. A predictive model of early-onset
preeclampsia included angiogenin/placental growth factor as a ratio, mean
arterial pressure, any pregnancy loss <10 weeks, and mean uterine artery
resistance index (area under the receiver operator curve [95% confidence
interval] in training and validation cohorts, 0.89 [0.78-1.0] and 0.78 [0.58
0.99], respectively). Neither model included pregnancy-associated plasma protein
A, previously reported to predict preeclampsia in populations of mixed parity and
risk. In nulliparous women, combining multiple biomarkers and clinical data
provided modest prediction of preeclampsia.
PMID- 25122932
TI - Breaking bones: one fracture can lead to another.
PMID- 25122934
TI - I recently developed proctitis after completing radiation treatment for prostate
cancer. What should I do?
PMID- 25122935
TI - What is an ESR and when is my doctor likely to order it?
PMID- 25122936
TI - Your medicine cabinet's best cold fighter.
PMID- 25122937
TI - A reason to cry over burnt toast.
PMID- 25122939
TI - Master new skills to retain memory.
PMID- 25122938
TI - A breakthrough in mantle cell lymphoma.
PMID- 25122940
TI - Servicemembers' Group Life Insurance--Veterans' Group Life Insurance regulation
update--ABO, VGLI application, SGLI 2-year disability extension. Final rule.
AB - This document amends the Department of Veterans Affairs (VA) insurance
regulations concerning Servicemembers' Group Life Insurance (SGLI) to reflect the
statutory provisions of the Veterans' Benefits Act of 2010, which became law on
October 13, 2010, and resulted in the need for amendments to change the SGLI
Disability Extension period from 1 year to 2 years in duration; provide SGLI
Traumatic Injury Protection (TSGLI) retroactive coverage effective from October
7, 2001, for all qualifying injuries regardless of the geographic location and
military operation in which the injuries were incurred; and remove the SGLI and
Veterans' Group Life Insurance (VGLI) Accelerated Benefits Option (ABO) discount
rate. This rule also clarifies that ''initial premium'' refers to ''initial
Veterans' Group Life Insurance premium,'' updates the current address of the
Office of Servicemembers' Group Life Insurance (OSGLI), managed by Prudential
Insurance Company of America, to reflect where the ABO application is mailed for
processing, and corrects the OSGLI phone number. Finally, this rule removes the
ABO application form from the regulation, and it corrects and clarifies language
concerning the VGLI application period that was inadvertently incorrectly
modified in a prior amendment of the regulations.
PMID- 25122941
TI - Medicare, Medicaid, and Children's Health Insurance Programs: announcement of the
extended temporary moratoria on enrollment of ambulance suppliers and home health
agencies in designated geographic locations. Extension of temporary moratoria.
AB - This document announces the extension of temporary moratoria on the enrollment of
new ambulance suppliers and home health agencies (HHAs) in specific locations
within designated metropolitan areas in Florida, Illinois, Michigan, Texas,
Pennsylvania, and New Jersey to prevent and combat fraud, waste, and abuse.
PMID- 25122942
TI - Schedule for rating disabilities--mental disorders and definition of psychosis
for certain VA purposes. Interim final rule.
AB - The Department of Veterans Affairs (VA) is amending the portion of its Schedule
for Rating Disabilities (VASRD) dealing with mental disorders and its
adjudication regulations that define the term ''psychosis.'' The VASRD refers to
the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM
IV), and VA's adjudication regulations refer to the Diagnostic and Statistical
Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR). DSM-IV and
DSM-IV-TR were recently updated by issuance of the Diagnostic and Statistical
Manual of Mental Disorders, Fifth Edition (DSM-5). This rulemaking will remove
outdated DSM references by deleting references to DSM-IV and DSM-IV-TR and
replacing them with references to DSM-5. Additionally, this rulemaking will
update the nomenclature used to refer to certain mental disorders to conform to
DSM-5.
PMID- 25122944
TI - Administrative simplification: change to the compliance date for the
International Classification of Diseases, 10th Revision (ICD-10-CM and ICD-10
PCS) medical data code sets. Final rule.
AB - This final rule implements section 212 of the Protecting Access to Medicare Act
of 2014 by changing the compliance date for the International Classification of
Diseases, 10th Revision, Clinical Modification (ICD-10-CM) for diagnosis coding,
including the Official ICD-10-CM Guidelines for Coding and Reporting, and the
International Classification of Diseases, 10th Revision, Procedure Coding System
(ICD-10-PCS) for inpatient hospital procedure coding, including the Official ICD
10-PCS Guidelines for Coding and Reporting, from October 1, 2014 to October 1,
2015. It also requires the continued use of the International Classification of
Diseases, 9th Revision, Clinical Modification, Volumes 1 and 2 (diagnoses), and 3
(procedures) (ICD-9-CM), including the Official ICD-9-CM Guidelines for Coding
and Reporting, through September 30, 2015.
PMID- 25122943
TI - Specifications for medical examinations of coal miners. Interim final rule.
AB - With this action, the Department of Health and Human Services (HHS), in
accordance with a final rule recently published by the Department of Labor's Mine
Safety and Health Administration (MSHA), is amending its regulations to establish
standards for the approval of facilities that conduct spirometry examinations and
to require that all coal mine operators submit a plan for the provision of
spirometry and X-ray examinations to all surface and underground coal miners.
PMID- 25122945
TI - Final priority; Technical Assistance on State Data Collection--IDEA Data
Management Center. Final priority.
AB - The Assistant Secretary for the Office of Special Education and Rehabilitative
Services (OSERS) announces a priority under the Technical Assistance on State
Data Collection program. The Assistant Secretary may use this priority for
competitions in fiscal year (FY) 2014 and later years. We take this action to
fund a cooperative agreement to establish and operate an IDEA Data Management
Center (Center) that will provide technical assistance (TA) to improve the
capacity of States to meet the data collection requirements of the Individuals
with Disabilities Education Act (IDEA).
PMID- 25122946
TI - Medicare program; prospective payment system and consolidated billing for skilled
nursing facilities for FY 2015. Final rule.
AB - This final rule updates the payment rates used under the prospective payment
system (PPS) for skilled nursing facilities (SNFs) for fiscal year (FY) 2015. In
addition, it adopts the most recent Office of Management and Budget (OMB)
statistical area delineations to identify a facility's urban or rural status for
the purpose of determining which set of rate tables will apply to the facility,
and to determine the SNF PPS wage index including a 1-year transition with a
blended wage index for all providers for FY 2015. This final rule also contains a
revision to policies related to the Change of Therapy (COT) Other Medicare
Required Assessment (OMRA). This final rule includes a discussion of a provision
related to the Affordable Care Act involving Civil Money Penalties. Finally, this
final rule discusses the SNF therapy payment research currently underway within
CMS, observed trends related to therapy utilization among SNF providers, and the
agency's commitment to accelerating health information exchange in SNFs.
PMID- 25122947
TI - Medicare program; inpatient rehabilitation facility prospective payment system
for federal fiscal year 2015.
AB - This final rule updates the prospective payment rates for inpatient
rehabilitation facilities (IRFs) for federal fiscal year (FY) 2015 as required by
the statute. This final rule finalizes a policy to collect data on the amount and
mode (that is, Individual, Concurrent, Group, and Co-Treatment) of therapy
provided in the IRF setting according to therapy discipline, revises the list of
diagnosis and impairment group codes that presumptively meet the "60 percent
rule'' compliance criteria, provides a way for IRFs to indicate on the Inpatient
Rehabilitation Facility-Patient Assessment Instrument (IRF-PAI) form whether the
prior treatment and severity requirements have been met for arthritis cases to
presumptively meet the "60 percent rule'' compliance criteria, and revises and
updates quality measures and reporting requirements under the IRF quality
reporting program (QRP). This rule also delays the effective date for the
revisions to the list of diagnosis codes that are used to determine presumptive
compliance under the "60 percent rule'' that were finalized in FY 2014 IRF PPS
final rule and adopts the revisions to the list of diagnosis codes that are used
to determine presumptive compliance under the "60 percent rule'' that are
finalized in this rule. This final rule also addresses the implementation of the
International Classification of Diseases, 10th Revision, Clinical Modification
(ICD-10-CM), for the IRF prospective payment system (PPS), which will be
effective when ICD-10-CM becomes the required medical data code set for use on
Medicare claims and IRF-PAI submissions.
PMID- 25122948
TI - Medicare program; inpatient psychiatric facilities prospective payment system-
update for fiscal year beginning October 1, 2014 (FY 2015). Final rule.
AB - This final rule will update the prospective payment rates for Medicare inpatient
hospital services provided by inpatient psychiatric facilities (IPFs). These
changes will be applicable to IPF discharges occurring during the fiscal year
(FY) beginning October 1, 2014 through September 30, 2015. This final rule will
also address implementation of ICD-10-CM and ICD-10-PCS codes; finalize a new
methodology for updating the cost of living adjustment (COLA), and finalize new
quality measures and reporting requirements under the IPF quality reporting
program.
PMID- 25122949
TI - Concentrations of mobile source air pollutants in urban microenvironments.
AB - Human exposures to criteria and hazardous air pollutants (HAPs) in urban areas
vary greatly due to temporal-spatial variations in emissions, changing
meteorology, varying proximity to sources, as well as due to building, vehicle,
and other environmental characteristics that influence the amounts of ambient
pollutants that penetrate or infiltrate into these microenvironments.
Consequently, the exposure estimates derived from central-site ambient
measurements are uncertain and tend to underestimate actual exposures. The
Exposure Classification Project (ECP) was conducted to measure pollutant
concentrations for common urban microenvironments (MEs) for use in evaluating the
results of regulatory human exposure models. Nearly 500 sets of measurements were
made in three Los Angeles County communities during fall 2008, winter 2009, and
summer 2009. MEs included in-vehicle, near-road, outdoor and indoor locations
accessible to the general public. Contemporaneous 1- to 15-min average personal
breathing zone concentrations of carbon monoxide (CO), carbon dioxide (CO2),
volatile organic compounds (VOCs), nitric oxide (NO), nitrogen oxides (NO(x)),
particulate matter (< 2.5 microm diameter; PM2.5) mass, ultrafine particle (UFP;
< 100 nm diameter) number black carbon (BC), speciated HAPs (e.g, benzene,
toluene, ethylbenzene, xylenes [BTEX], 1,3-butadiene), and ozone (O3) were
measured continuously. In-vehicle and inside/outside measurements were made in
various passenger vehicle types and in public buildings to estimate penetration
or infiltration factors. A large fraction of the observed pollutant
concentrations for on-road MEs, especially near diesel trucks, was unrelated to
ambient measurements at nearby monitors. Comparisons of ME concentrations
estimated using the median ME/ambient ratio versus regression slopes and
intercepts indicate that the regression approach may be more accurate for on-road
MEs. Ranges in the ME/ambient ratios among ME categories were generally greater
than differences among the three communities for the same ME category, suggesting
that the ME proximity factors may be more broadly applicable to urban MEs.
Implications: Estimates of population exposure to air pollutants extrapolated
from ambient measurements at ambient fixed site monitors or exposure surrogates
are prone to uncertainty. This study measured concentrations of mobile source air
toxics (MSAT) and related criteria pollutants within in-vehicle, outdoor near
road, and indoor urban MEs to provide multipollutant ME measurements that can be
used to calibrate regulatory exposure models.
PMID- 25122950
TI - Investigation of time-resolved atmospheric conditions and indoor/outdoor
particulate matter concentrations in homes with gas and biomass cook stoves in
Nogales, Sonora, Mexico.
AB - This paper reports findings from a case study designed to investigate indoor and
outdoor air quality in homes near the United States-Mexico border During the
field study, size-resolved continuous particulate matter (PM) concentrations were
measured in six homes, while outdoor PM was simultaneously monitored at the same
location in Nogales, Sonora, Mexico, during March 14-30, 2009. The purpose of the
experiment was to compare PM in homes using different fuels for cooking, gas
versus biomass, and to obtain a spatial distribution of outdoor PM in a region
where local sources vary significantly (e.g., highway, border crossing, unpaved
roads, industry). Continuous PM data were collected every 6 seconds using a valve
switching system to sample indoor and outdoor air at each home location. This
paper presents the indoor PM data from each home, including the relationship
between indoor and outdoor PM. The meteorological conditions associated with
elevated ambient PM events in the region are also discussed. Results indicate
that indoor air pollution has a strong dependence on cooking fuel, with gas
stoves having hourly averaged median PM3 concentrations in the range of 134 to
157 microg m(-3) and biomass stoves 163 to 504 microg m(-1). Outdoor PM also
indicates a large spatial heterogeneity due to the presence of microscale sources
and meteorological influences (median PM3: 130 to 770 microg m(-3)). The former
is evident in the median and range of daytime PM values (median PM3: 250 microg
m(-3), maximum: 9411 microg m(-3)), while the meteorological influences appear to
be dominant during nighttime periods (median PM3: 251 microg m(-3), maximum:
10,846 microg m(-3)). The atmospheric stability is quantified for three nighttime
temperature inversion episodes, which were associated with an order of magnitude
increase in PM10 at the regulatory monitor in Nogales, AZ (maximum increase: 12
to 474 microg m(-3)). Implications: Regulatory air quality standards are based on
outdoor ambient air measurements. However, a large fraction of time is typically
spent indoors where a variety of activities including cooking, heating, tobacco
smoking, and cleaning can lead to elevated PM concentrations. This study
investigates the influence of meteorology, outdoor PM, and indoor activities on
indoor air pollution (IAP) levels in the United States-Mexico border region.
Results indicate that cooking fuel type and meteorology greatly influence the IAP
in homes, with biomass fuel use causing the largest increase in PM concentration.
PMID- 25122951
TI - Role of sodium ions in the vitrification process: glass matrix modification, slag
structure depolymerization, and influence of metal immobilization.
AB - This study investigates the role of Na ions, a common flux, in the vitrification
process. Artificial glass systems composed of Al2O3, CaO, and SiO2 with various
Na concentrations were melted at 1450 degrees C. The specimens were cooled by air
cooling and water quenching and the metal mobility was evaluated using a
sequential extraction procedure. The X-ray diffraction analysis and scanning
electron microscopy observations showed that Na ions governed the air-cooled
slag's structure. Na ions initially depolymerized CaSiO3-linked chains into
CaSiO3 chains, and further cut them into shorter and nonuniform ones, making the
slag structure amorphous. With even more Na ions, CaSiO3 chains were divided into
single SiO4 tetrahedrons and formed Na-related crystals (Na2Ca3Si2O8 and
NaAlSiO4). The phase distributions of Al, Cr, Cu Mn, and Ni showed that Na has a
positive effect on the immobilization of heavy metals at suitable concentrations,
but a negative effect when in excess amounts. Implications: Vitrification has
been widely used to treat hazardous materials. The Na-bearing additives were
often used as a flux to improve the melting process. This study described the
role of Na played in the vitrification process. The Na ions acted as glass
modifier and depolymerize the chain structure of slag. With adequate addition
amount of Na ions, the immobilization of heavy metals was improved. The results
provided much information about the crystalline phase variation, metal mobility,
and surface characteristics while Na serves as a flux.
PMID- 25122952
TI - Particle size distribution and its relationship to black carbon in two urban and
one rural site in Santiago de Chile.
AB - The size distribution of particles has been studied in three sites in the
Metropolitan area of Santiago de Chile in the winter of 2009 and a comparison
with black carbon was performed. Two sites are located near busy streets in
Santiago and the other site is located in a rural area about 40 km west of
Santiago with little influence from vehicles, but large influence from wood
burning. The campaign lasted 1 or 2 weeks in each site. We have divided the
particle size measurements into four groups (10-39 nm, 40-62 nm, 63-174 nm, and
175-700 nm) in order to compare with the carbon monitor. In the sites near the
street, black carbon has a high correlation (R = 0.85) with larger particles (175
700 nm). The correlation decreased when black carbon was compared with smaller
particles, having very small correlation with the smallest sizes (10-39 nm). In
the rural site, black carbon also has a high correlation (R = 0.86) with larger
particles (175-700 nm), but the correlation between black carbon and the finest
particles (10-39 nm) decreases to near 0. These measurements are an indication
that wood burning does not generate particles smaller than -50 nm. In the urban
sites, particle size distribution is peaked toward smaller particles (10-39 nm)
only during rush hours, but at other times, particles size distribution is peaked
toward larger sizes. When solar radiation was high, evidence of secondary
particle formation was seen in the rural site, but not in the urban sites. The
correlation between the number of secondary particles and solar radiation was R2
= 0.46, indicating that it there may be other variables that play a role in
ultrafine particle formation. Implications: A study of the size distribution of
particles and black carbon concentration in two street sites and one rural site
shows that in the last site the number of particles ultrafine particles (d < 40
nm) is 10 times lower but the number of larger particles is about 2 times lower.
Thus, the rural site has less of the particles that are more dangerous to health.
The number ofultrafine particles is mostly associated with traffic, while the
number of larger particles is associated with wood burning and other sources.
Wood burning does not generate particles smaller than -50 nm.
PMID- 25122953
TI - Recovering valuable metals from recycled photovoltaic modules.
AB - Recovering valuable metals such as Si, Ag, Cu, and Al has become a pressing issue
as end-of-life photovoltaic modules need to be recycled in the near future to
meet legislative requirements in most countries. Of major interest is the
recovery and recycling of high-purity silicon (> 99.9%) for the production of
wafers and semiconductors. The value of Si in crystalline-type photovoltaic
modules is estimated to be -$95/kW at the 2012 metal price. At the current
installed capacity of 30 GW/yr, the metal value in the PV modules represents
valuable resources that should be recovered in the future. The recycling of end
of-life photovoltaic modules would supply > 88,000 and 207,000 tpa Si by 2040 and
2050, respectively. This represents more than 50% of the required Si for module
fabrication. Experimental testwork on crystalline Si modules could recover a >
99.98%-grade Si product by HNO3/NaOH leaching to remove Al, Ag, and Ti and other
metal ions from the doped Si. A further pyrometallurgical smelting at 1520
degrees C using CaO-CaF2-SiO2 slag mixture to scavenge the residual metals after
acid leaching could finally produce > 99.998%-grade Si. A process based on
HNO3/NaOH leaching and subsequent smelting is proposed for recycling Si from
rejected or recycled photovoltaic modules. Implications: The photovoltaic
industry is considering options of recycling PV modules to recover metals such as
Si, Ag, Cu, Al, and others used in the manufacturing of the PV cells. This is to
retain its "green" image and to comply with current legislations in several
countries. An evaluation of potential resources made available from PV wastes and
the technologies used for processing these materials is therefore of significant
importance to the industry. Of interest are the costs of processing and the
potential revenues gained from recycling, which should determine the viability of
economic recycling of PV modules in the future.
PMID- 25122954
TI - Trends in on-road vehicle emissions and ambient air quality in Atlanta, Georgia,
USA, from the late 1990s through 2009.
AB - On-road vehicle emissions of carbon monoxide (CO), nitrogen oxides (NO(x)), and
volatile organic compounds (VOCs) during 1995-2009 in the Atlanta Metropolitan
Statistical Area were estimated using the Motor Vehicle Emission Simulator
(MOVES) model and data from the National Emissions Inventories and the State of
Georgia. Statistically significant downward trends (computed using the
nonparametric Theil-Sen method) in annual on-road CO, NO(x), and VOC emissions of
6.1%, 3.3%, and 6.0% per year, respectively, are noted during the 1995-2009
period despite an increase in total vehicle distance traveled. The CO and NO(x)
emission trends are correlated with statistically significant downward trends in
ambient air concentrations of CO and NO(x) in Atlanta ranging from 8.0% to 11.8%
per year and from 5.8% to 8.7% per year, respectively, during similar time
periods. Weather-adjusted summertime ozone concentrations in Atlanta exhibited a
statistically significant declining trend of 2.3% per year during 2001-2009.
Although this trend coexists with the declining trends in on-road NO(x), VOC, and
CO emissions, identifying the cause of the downward trend in ozone is complicated
by reductions in multiple precursors from different source sectors. Implications:
Large reductions in on-road vehicle emissions of CO and NO(x) in Atlanta from the
late 1990s to 2009, despite an increase in total vehicle distance traveled,
contributed to a significant improvement in air quality through decreases in
ambient air concentrations of CO and NO(x) during this time period. Emissions
reductions in motor vehicles and other source sectors resulted in these
improvements and the observed declining trend in ozone concentrations over the
past decade. Although these historical trends cannot be extrapolated to the
future because pollutant concentration contributions due to on-road vehicle
emissions will likely become an increasingly smaller fraction of the atmospheric
total, they provide an indication of the benefits of past control measures.
PMID- 25122955
TI - Annual and weekly patterns of ozone and particulate matter in Jeddah, Saudi
Arabia.
AB - Air pollution has been an increasing concern within the Kingdom of Saudi Arabia
and other Middle Eastern countries. In this work the authors present an analysis
of daily ozone (O3), nitrogen oxide (NO(x)), and particulate matter (< 10 miccrom
aerodynamic diameter; PM10) concentrations for two years (2010 and 2011) at sites
in and around the coastal city of Jeddah, as well as a remote background site for
comparison. Monthly and weekly variations, along with their implications and
consequences, were also examined. O3 within Jeddah was remarkably low, and
exhibited the so-called weekend effect--elevated O3 levels on the weekends,
despite reduced emissions of O3 precursors on those days. Weekend O3 increases
averaged between 12% and 14% in the city, suggesting that NO(x)/volatile organic
compound (VOC) ratios within cities such as Jeddah may be exceptionally high.
Sites upwind or far removed from Jeddah did not display this weekend effect.
Based on these results, emission control strategies in and around Jeddah must
carefully address NO(x)/VOC ratios so as to reduce O3 at downwind locations
without increasing it within urban locations themselves. PM10 concentrations
within Jeddah were elevated compared with North American cites of similar
climatology though comparable to other large cities within the Middle East.
Implications: Daily concentrations of O3, PM10, and NO(x) in and around the city
of Jeddah, Saudi Arabia, are analyzed and compared with those of other reference
cities. Extremely low O3 levels, along with a significant urban weekend effect
(higher weekend O3, despite reduced NO(x) concentrations), is apparent, along
with high levels of PM10 within the city. Urban O3 in Jeddah was found to be
lower than that of other comparable cities, but the strong weekend effect
suggests that care must be taken to reduce downwind O3 levels without increasing
them within the city itself. Further research into the emissions and chemistry
contributing to the reduced O3 levels within the city is warranted.
PMID- 25122956
TI - Carbon dioxide adsorption on amine-impregnated mesoporous materials prepared from
spent quartz sand.
AB - Mesoporous MCM-41 was synthesized using cetyltrimethyl ammonium bromide (CTAB) as
a cationic surfactant and spent quartz sand as the silica source. Modification of
the mesoporous structure to create an absorbent was then completed using 3
aminopropyltrimethoxysilane. Amine-Quartz-MCM (The A-Q-MCM) adsorbents were then
characterized by N2 adsorption/desorption, elemental analysis (EA), X-ray
fluorescence (XRF), scanning electron microscopy (SEM), Fourier transform
infrared spectroscopy (FTIR), as well as the carbon dioxide (CO2)
adsorption/desorption performance. In this study, spent quartz sand was utilized
to synthesize Quartz-MCM (Q-MCM) and the amine functionalized material, A-Q-MCM,
which exhibited a higher uptake of CO2 at room temperature compared with the
nongrafted material. The results showed that Q-MCM is similar to MCM-41
synthesized using commercial methods. The surface area, pore volume, and pore
diameter were found to be as high as 1028 m2/g, 0.907 cm3/g, and 3.04 nm,
respectively. Under the condition of CO2 concentration of 5000 ppm, retention
time of 50 cc/min, and the dosage of 1 g/cm3, the mean adsorption capacity of CO2
onto A-Q-MCM was about 89 mg/g, and the nitrogen content of A-Q-MCM was 2.74%.
The adsorption equilibrium was modeled well using a Freundlich isotherm.
Implications: In this study, spent quartz sand was utilized to synthesize Q-MCM.
The amine functionalized material exhibited a higher uptake of CO2 at room
temperature compared with the nongrafted material. The results showed that Q-MCM
is similar to MCM-41 synthesized using commercial methods. The adsorption
equilibrium was modeled well using a Freundlich isotherm.
PMID- 25122957
TI - Emission, speciation, and evaluation of impacts of non-methane volatile organic
compounds from open dump site.
AB - Surface emission from Dhapa, the only garbage disposal ground in Kolkata, is a
matter of concern to the local environment and also fuels the issues of
occupational and environmental health. Surface emission of the Dhapa landfill
site was studied using a flux chamber measurement for nonmethane volatile organic
compounds (NMVOCs). Eighteen noncarbonyl volatile organic compounds (VOCs) and 14
carbonyl VOCs, including suspected and known carcinogens, were found in
appreciable concentrations. The concentrations of the target species in the flux
chamber were found to be significantly higher for most of the species in summer
than winter. Surface emission rate of landfill gas was estimated by using two
different approaches to assess the applicability for an open landfill site. It
was found that the emissions predicted using the model Land GEM version 3.02 is
one to two orders less than the emission rate calculated from flux chamber
measurement for the target species. Tropospheric ozone formation has a serious
impact for NMVOC emission. The total ozone-forming potential (OFP) of the Dhapa
dumping ground considering all target NMVOCs was estimated to be 4.9E+04 and
1.2E+05 g/day in winter and summer, respectively. Also, it was found that
carbonyl VOCs play a more important role than noncarbonyl VOCs for tropospheric
ozone formation. Cumulative cancer risk estimated for all the carcinogenic
species was found to be 2792 for 1 million population, while the total noncancer
hazard index (HI) was estimated to be 246 for the occupational exposure to
different compounds from surface emission to the dump-site workers at Dhapa.
Implications: This paper describes the real-time surface emission of NMVOCs from
an open municipal solid waste (MSW) dump site studied using a flux chamber. Our
study findings indicate that while planning for new landfill site in tropical
meteorology, real-time emission data must be considered, rather than relying on
modeled data. The formation of tropospheric ozone from emitted NMVOC has also
been studied. Our result shows how an open landfill site acts as a source and
adds to the tropospheric ozone for the airshed of a metropolitan city.
PMID- 25122958
TI - A comprehensive study on landfill site selection for Kolkata City, India.
AB - Kolkata is one of the four major metropolitan cities in India and the capital
city of the state of West Bengal. With an area of 187.33 km2 and a population of
about 10 million (including a floating population of about 6 million), the city
generates about 3500 Metric Ton (MT) of solid waste per day. Currently, Kolkata
Municipal Corporation (KMC) disposes its waste at Dhapa (21.47 ha), where the
disposal rate exceeds 3000 MT/day, and at Garden Reach (3.52 ha), where the
disposal rate is 100 MT/day. Considering the exhaustion of Dhapa land space, city
planners are urgently searching for an alternate disposal ground. National
Environmental Engineering Research Institute (NEERI), under the sponsorship of
Central Pollution Control Board (CPCB), has brought out literature developing the
site selection criteria for municipal solid waste disposal ground to suit Indian
conditions. The developed criteria encompass environmental conditions,
accessibility, geological and hydrogeological conditions, and ecological and
societal effects. This paper attempts to locate the most suitable site for
disposal of KMC area solid waste using the multicriterion decision analysis as
stipulated in CPCB 2003 guidelines and the overlay analysis of geographic
information system (GIS). Implications: The paper is based on landfill site
selection for dumping of solid waste generated within Kolkata Municipal
Corporation (KMC) area. The methodology uses GIS/remote sensing, Site Sensitivity
Index (an offshoot of pairwise comparison technique developed in CPCB 2003
guidelines, Government of India), and the Delphi technique. Dhapa landfill site,
where solid waste of KMC area is currently being disposed, is exhausted; the
authors of this article thus found it relevant to carry out a research on the
selection of an alternative landfill site. The study undertaken was
comprehensive, yet presented in a lucid way so that policymakers will find easy
to comprehend.
PMID- 25122959
TI - A personal reflection on our future leaders.
PMID- 25122960
TI - Generation to generation. Jesus, formation and transitions in leadership.
PMID- 25122961
TI - CHI's formation initiatives. Programs help embed core values.
PMID- 25122962
TI - Storytelling moves learning from head to heart to feet.
PMID- 25122963
TI - The sounds of Project ECHO.
PMID- 25122964
TI - Measuring ministry formation. Moving promise into practice.
PMID- 25122965
TI - Tomorrow's Leaders, Class of 2014.
PMID- 25122966
TI - Catching up with two leaders from the Class of 2011.
PMID- 25122967
TI - Interview with Richard Gilfillan, MD. How leadership will empower ministry's move
to population health.
PMID- 25122968
TI - Preliminary results. CHA survey gauges formation effectiveness.
PMID- 25122969
TI - Celebrating 100 years.
PMID- 25122970
TI - The growth of systems. Unprecedented challenges.
PMID- 25122971
TI - What we have here is a failure to communicate. The ethical dimension of health
literacy.
PMID- 25122972
TI - Add ethical decision-making to the planning process.
PMID- 25122973
TI - Norms for canonical elections.
PMID- 25122974
TI - Setting donation standards for surplus.
PMID- 25122975
TI - Comparative plaque removal efficacy of two new powered toothbrushes and a manual
toothbrush.
AB - OBJECTIVE: The purpose of this study was to determine the plaque-reducing
effectiveness of two new powered toothbrushes and compare them to a manual
toothbrush control. METHODS: This examiner-blind, randomized study used a
crossover design. Sixty-five qualifying male and female subjects were randomly
assigned one of the two test powered brushes (Spinbrush Truly Radiant Deep Clean
[TRDC] or Spinbrush Truly Radiant Extra Whitening [TREW], Church & Dwight Co.,
Inc., Princeton, NJ, USA) or an ADA standard manual toothbrush (MT; American
Dental Association, Chicago, IL, USA) according to one of three computer
generated sequences. Following instruction in the use of their assigned
toothbrush, subjects brushed at home with a standard fluoride toothpaste twice
daily for two minutes during a one-week familiarization period. At the end of
this period, the subjects returned to the study site after refraining from oral
hygiene for 12-16 hours, and from eating, drinking, and smoking for four hours.
Plaque was scored using the Rustogi Modification of the Navy Plaque Index.
Subjects brushed under supervision with their assigned toothbrush for two
minutes, and plaque was rescored. They were then given one of the alternate
toothbrushes according to their assigned sequence, and the familiarization
routine and evaluation processes were repeated until each of the subjects used
each of the three brushes. RESULTS: Within-group analyses showed that all three
toothbrushes produced statistically significant reductions from the pre-brushing
baseline in whole mouth and regional plaque scores (p < 0.001), with respective
whole mouth reductions of 17.9%, 42.3%, and 38.1% for MT, TRDC, and TREW. Between
group analyses showed that TRDC and TREW were each significantly more effective
(p < 0.001) than MT, as each showed at least twice as much of a reduction in
whole mouth scores. Both of the powered brushes also produced statistically
significantly greater reductions than the manual brush at each of the twelve
subsets of sites examined, with the greatest differences at interpoximal sites
and sites presenting access difficulty, such as those in the lingual posterior
region. Additionally, TRDC produced a statistically significant 11.5% greater
reduction than TREW (p = 0.001) in whole mouth plaque scores, and statistically
significantly greater reductions in two of the subsets evaluated. CONCLUSION:
Both of the powered brushes tested proved to be safe and significantly more
effective than the standard manual control brush in reducing plaque. While the
finding that the TRDC was significantly more effective than the TREW in reducing
whole mouth plaque and plaque in two subsets demonstrates that small differences
in toothbrush design may impact performance, longer-term studies would be needed
to assess the extent to which this translates to meaningful clinical outcomes.
PMID- 25122976
TI - A six-week clinical evaluation of the plaque and gingivitis efficacy of an
oscillating-rotating power toothbrush with a novel brush head utilizing angled
CrissCross bristles versus a sonic toothbrush.
AB - OBJECTIVE: To compare the efficacy of an oscillating-rotating power toothbrush
with a novel brush head incorporating angled CrissCross bristles (Oral-B Triumph
with SmartGuide with Oral-B CrossAction brush head) versus a sonic toothbrush
(Sonicare DiamondClean) for plaque and gingivitis reduction over a six-week
period. METHODS: This was a single-center, randomized, examiner-blind, two
treatment, parallel group study involving 65 subjects per group. Subjects
presenting with mild-to-moderate gingivitis at Baseline were randomly assigned to
either the oscillating-rotating brush or the sonic brush. They were instructed to
use their assigned toothbrush and a standard fluoride dentifrice for two minutes
twice daily at home for six weeks. Gingivitis and plaque were assessed at
Baseline and Week 6 using the Modified Gingival Index (MGI), Gingival Bleeding
Index (GBI), and Rustogi Modified Navy Plaque Index (RMNPI). Data were analyzed
using an Analysis of Covariance (ANCOVA), with baseline as the covariate.
Subjects also completed a consumer perception questionnaire to evaluate their
brushing experience. RESULTS: One-hundred and thirty subjects were enrolled in
the study and randomized to treatment. Sixty-four subjects per group completed
the trial. Both brushes produced statistically significant reductions in
gingivitis and plaque measures at Week 6 relative to Baseline (p < 0.001 for
all). The oscillating-rotating brush with the novel brush head demonstrated
statistically significantly greater reductions in all gingivitis and plaque
measures compared to the sonic toothbrush. The benefits for the oscillating
rotating brush over the sonic brush were 32.6% for gingivitis, 35.4% for gingival
bleeding, 32% for number of bleeding sites, 22% for whole mouth plaque, 24.2% for
gingival margin plaque, and 33.3% for approximal plaque (p < or = 0.001 for all
measures except gingival margin plaque, where p = 0.018). Analysis of the
consumer perception questionnaire results showed subjects using the oscillating
rotating brush rated it higher for overall use experience and key attributes
related to cleaning, gentleness, and brush head shape/size versus subjects in the
sonic brush group. There were no adverse events reported or observed for either
brush. CONCLUSION: This six-week randomized, examiner-blind, comparative clinical
study showed the oscillating-rotating toothbrush, with a novel brush head
incorporating angled CrissCross bristles, was significantly better than an
advanced sonic power toothbrush at reducing gingival inflammation and bleeding,
as well as reducing whole mouth plaque, plaque along the gumline, and in the
approximal regions.
PMID- 25122977
TI - A clinical study to assess the effect of a stabilized stannous fluoride
dentifrice on hypersensitivity relative to a marketed sodium fluoride/triclosan
control.
AB - OBJECTIVE: To evaluate the efficacy of a marketed stabilized stannous fluoride
(SnF2) dentifrice in reducing dentinal hypersensitivity as compared to a marketed
sodium fluoride (NaF)/triclosan dentifrice over an eight-week period. METHODS:
Adults with confirmed dentinal hypersensitivity were enrolled in this randomized
and controlled, parallel group, double blind, eight-week, single-center clinical
trial. Random assignment to one of two dentifrice test groups via age, gender,
and thermal sensitivity of enrolled test teeth was performed at baseline, with
subjects assigned to twice-daily unsupervised brushing with either the marketed
SnF2 dentifrice (Oral-B Pro-Expert, 0.454% SnF2 plus 0.077% NaF) or the marketed
0.32% NaF with 0.3% triclosan/copolymer dentifrice control (Colgate Total
Advanced). Tactile sensitivity (Yeaple Probe) and thermal sensitivity
(airblast/Schiff Air Index) evaluations of the selected test teeth were performed
at baseline pre-treatment, and again at Weeks 2 and 8 of product use to compare
the dentifrices' relative hypersensitivity protection effectiveness. RESULTS:
Ninety-seven (97) of the 100 enrolled subjects completed the trial and were fully
evaluable. At both Week 2 and Week 8, for both the thermal and tactile evaluation
measurements, subjects brushing with the marketed SnF2 dentifrice experienced
statistically significantly (p < 0.0001) superior average dentinal
hypersensitivity improvement versus subjects assigned to the NaF/triclosan
control dentifrice. Between groups, superior relative mean reduction in thermal
Schiff Air Index favored SnF2 by 24% at Week 2 and 68% at Week 8, while greater
relative mean tactile Yeaple Probe benefits were observed for SnF2 relative to
the control by 114% after Week 2 and 184% at Week 8. The dentifrices were well
tolerated. CONCLUSION: Twice-daily brushing with a marketed SnF2 dentifrice
provided superior dentinal hypersensitivity improvement versus a commercially
available NaF/triclosan dentifrice, with significantly (p < 0.0001) greater
relief after two weeks, and even larger relative benefits at eight weeks.
PMID- 25122978
TI - Brush head composition, wear profile, and cleaning efficacy: an assessment of
three electric brush heads using in vitro methods.
AB - OBJECTIVE: The objective of this research was to evaluate a current store brand
(SB) brush head for composition/physical characteristics, Wear Index (WI), and
cleaning efficacy versus the previous SB brush head refill design (SB control)
and the Oral-B Precision Clean brush head (positive control, PC). METHODS: This
research consisted of three parts: 1) Analytical analysis using Fourier Transform
Infrared (FT-IR) spectrometry to evaluate the chemical composition of the current
SB brush head bristles relative to the SB control. In addition, physical
parameters such as bristle count and diameter were determined. 2) Wear Index (WI)
investigation to determine the Wear Index scores of in vitro-aged brush heads at
four weeks (one month) and 13 weeks (three months) by a trained investigator. To
"age" the brush heads, a robot system was used as a new alternative in vitro
method to simulate aging by consumer use. 3) Robot testing to determine the
cleaning performance of in vitro-aged brush heads, comparing one month-aged
current SB brush heads with the SB control (one and three months-aged) and the PC
brush heads (three months-aged) in a standardized fashion. RESULTS: 1) FT-IR
analysis revealed that the chemical composition of the current and control SB
refill brush heads is identical. In terms of physical parameters, the current SB
brush head has 12% more bristles and a slightly oval brush head compared to the
round brush head of the SB control. 2) Wear Index analysis showed there was no
difference in the one month-aged current SB brush head versus the one month-aged
SB control (1.67 vs. 1.50, p = 0.65) or versus the three months-aged PC brush
head (1.67 vs. 1.50, p = 0.65). The one month-aged current SB brush head
demonstrated statistically significantly less wear than the three months-aged SB
control (1.67 vs. 2.67, p = 0.01). 3) Analysis of cleaning efficacy shows that
the one month-aged current SB brush head had improved cleaning performance over
the one month-aged SB control brush head (p < 0.05), despite no statistically
significant difference in wear. Both the one month-aged current and control SB
brush heads showed statistically significantly lower cleaning performance
compared to the three months-aged PC brush heads (p < 0.01). CONCLUSION: While
the current SB brush head showed improved cleaning over the SB control, it
demonstrated significantly lower durability and cleaning in comparison to the PC
brush head. Dental professionals should be aware of these differences, both in
durability and in cleaning performance, when recommending brush heads to their
patients.
PMID- 25122979
TI - A randomized 12-week clinical comparison of an oscillating-rotating toothbrush to
a new sonic brush in the reduction of gingivitis and plaque.
AB - OBJECTIVE: To evaluate the efficacy of a marketed oscillating-rotating (O-R)
power toothbrush (Oral-B Triumph with SmartGuide and FlossAction brush head,
D34/EB25) to a new sonic toothbrush (Sonicare FlexCare Platinum) in the reduction
of gingivitis and plaque over a 12-week test period. METHODS: This was a single
center, randomized, open label, examiner-blind, two-treatment, parallel group
study. Subjects who met the entrance criteria were enrolled in the study and
randomly assigned to either the O-R or sonic treatment group. Subjects brushed
with their assigned toothbrush and a marketed fluoride dentifrice for two minutes
twice daily at home for 12 weeks. Gingivitis and plaque were evaluated at
Baseline, Week 6, and Week 12. Gingivitis was assessed using the Modified
Gingival Index (MGI) and Gingival Bleeding Index (GBI), and plaque was assessed
using the Rustogi Modified Navy Plaque Index (RMNPI). Data were analyzed using an
Analysis of Covariance (ANCOVA) with Baseline as the covariate. RESULTS: In
total, 130 subjects (65 per group) were randomized to treatment and 127 subjects
completed the study. Both brushes produced statistically significant (p < 0.001)
reductions in gingivitis and plaque measures relative to Baseline. At Week 12,
the O-R brush demonstrated significantly greater reductions than the sonic brush
in whole mouth gingivitis measures (p = 0.007). Additionally, the O-R brush
presented significantly fewer bleeding sites (p < 0.007) and significantly
greater reductions in whole mouth plaque measures (p < or = 0.035) at Weeks 6 and
12 versus the sonic brush. The benefit for the O-R brush versus the sonic brush
at Week 12 was 11.7% for gingivitis, 19.8% for number of bleeding sites, and
12.2% for whole mouth plaque. There were no adverse events reported or observed
for either brush. CONCLUSION: The oscillating-rotating toothbrush demonstrated
statistically significantly greater reductions in whole mouth plaque at Weeks 6
and 12, as well as significantly greater gingivitis reductions over the long-term
(12 weeks), compared to the new sonic toothbrush.
PMID- 25122980
TI - A clinical study of the efficacy of a new chewing gum containing calcium
hydroxyapatite in reducing dentin hypersensitivity.
AB - OBJECTIVE: A controlled, clinical, double blind study was conducted to assess the
efficacy of a sugar-free chewing gum containing calcium hydroxyapatite on dentin
hypersensitivity, versus a placebo chewing gum with no active ingredients, after
one and two weeks. METHODS: One hundred and seven subjects joined the trial and
were allocated into the test or the control (placebo) group by a random table.
The test chewing gum contained calcium hydroxyapatite and dicalcium phosphate
dihydrate; the control chewing gum was identical, but without those ingredients.
Participants were required to chew two pieces of their assigned chewing gum three
times a day. Dentin hypersensitivity was evaluated following three clinical test
indexes (tactile, air blast, cold water) and one subjective index. RESULTS: One
hundred subjects completed the study with 50 allocated to each group. The
clinical test index reductions after one and two weeks in the test group were,
respectively, 36% and 54% for tactile, 35% and 66% for air blast, and 24% and 49%
for cold water. The clinical test index reductions after one and two weeks in the
control group were, respectively, 16% and 30% for tactile, 11% and 25% for air
blast, and 14% and 31% for cold water. These reductions at one and two weeks were
significant for the test group (p < 0.01). For the control group they were
significant (p < 0.01) only at two weeks. The comparisons between the groups at
two weeks showed a significant statistical difference between the test and the
control gum for tactile (p < 0.01), for air blast (p < 0.001), for cold water (p
< 0.05), and for the subjective index (p < 0.05). CONCLUSION: In this trial, the
group using the chewing gum containing calcium hydroxyapatite had a statistically
significant reduction in all clinical test indexes for dentin hypersensitivity
after one and two weeks, and a statistically significant reduction compared to
the control gum group.
PMID- 25122981
TI - Psychotherapy supervision developments and innovations for the new millennium:
contributions from the cutting edge.
AB - What are some of the most recent, cutting-edge developments and innovations in
psychotherapy supervision? And what is their particular significance for
supervision now and into its future? In this special supervision issue of the
American Journal of Psychotherapy, those questions are considered, and some
compelling answers are provided. In what follows, I introduce this special
journal issue: (a) define supervision and indicate its purposes; (b) summarize
the contents of each innovative paper; and (c) accentuate the significance of
each presented development/innovation. The papers contained in this issue boldly
speak to supervision's future and provide exciting--and highly profitable-
directions to pursue in forever making psychotherapy supervision a far more
anchored, accountable, and educational experience.
PMID- 25122982
TI - Best Practices in Clinical Supervision: another step in delineating effective
supervision practice.
AB - Across the helping professions, we have arrived at a point where it is possible
to create statements of best practices in supervision that are based on available
empirical research; credentialing, ethical, and legal guidelines; and consensus
opinion. Best practices are different from, but certainly complementary to,
statements of supervision competencies. In this paper, I highlight the
differences between competencies and best practices, and then describe the
development and content of one comprehensive statement, the Best Practices in
Clinical Supervision created for the field of counseling and counselor education.
I then illustrate the applicability of the Best Practices across disciplines and
countries through a comparison and contrast with several other existing
documents. I conclude with a brief look at the development of supervisor
expertise, which requires not only declarative knowledge (competencies) and
procedural knowledge (statements of best practices), but also reflective
knowledge. The latter is composed of insights built over years of supervision
education, experience, and self-reflection regarding necessary adaptions and
improvisations that inform an individualized approach to supervision practice.
PMID- 25122983
TI - Using learning objectives for psychotherapy supervision.
AB - Although learning objectives, often in the form of competencies, are now standard
for training mental health professionals, they are not generally used to guide
psychotherapy supervision. Nevertheless, when learning objectives are not used to
guide supervision, supervisors and supervisees often remain uncertain about the
goals of supervision, how those goals should be attained, and how they should be
assessed. In this paper we review the literature on learning objectives for
psychotherapy training and supervision, outline reasons for using learning
objectives in psychotherapy supervision, and suggest ways to use learning
objectives in training.
PMID- 25122984
TI - Evaluation of psychology practitioner competence in clinical supervision.
AB - There is a growing consensus favouring the development, advancement, and
implementation of a competency-based approach for psychology training and
supervision. There is wide recognition that skills, attitude-values, and
relationship competencies are as critical to a psychologist's competence as are
knowledge capabilities, and that these key competencies are best measured during
placements, leaving the clinical supervisor in an unparalleled position of
advantage to provide formative and summative evaluations on the supervisee's
progression towards competence. Paradoxically, a compelling body of literature
from across disciplines indicates that supervisor ratings of broad domains of
competence are systematically compromised by biases, including leniency error and
halo effect. The current paper highlights key issues affecting summative
competency evaluations by supervisors: what competencies should be evaluated, who
should conduct the evaluation, how (tools) and when evaluations should be
conducted, and process variables that affect evaluation. The article concludes by
providing research recommendations to underpin and promote future progress and by
offering practice recommendations to facilitate a more credible and meaningful
evaluation of competence and competencies.
PMID- 25122985
TI - The use of supervision notes as a targeted training strategy.
AB - Despite a call for more training of clinical supervisors, little has emerged in
the professional literature to offer pedagogical strategies for training. This
article describes the use of supervision documentation to guide the development
of supervisors-in-training (SITs). Specifically, supervision notes are used to
assist and monitor SITs understanding and application of supervisor models.
PMID- 25122986
TI - Beyond the "acid test": a conceptual review and reformulation of outcome
evaluation in clinical supervision.
AB - Theoretical models abound within clinical supervision, but these rarely have been
applied to supervision evaluation. Instead, it appears that reviewers and
researchers have simply transferred to supervision the conceptual frameworks used
within medicine, especially the idea that clinical outcomes are the "acid test"
of supervisory effectiveness or quality. Following a careful examination of the
key literature, in this paper I argue that this has led to an over-emphasis on
clinical outcomes, with the net effect of reducing scientific confidence,
understanding, and the effectiveness of supervision. To begin to rectify this
bias, an augmented fidelity framework is used to reformulate evaluation, drawing
on some of the key concepts guiding evaluation within related fields (i.e.
service evaluation; staff development; psychotherapy; applied research). The
resulting evaluation model is specific to clinical supervision and can help to
increase our understanding, enhance our practice, re-prioritise research, and
inspire confidence in supervision.
PMID- 25122987
TI - Videoconference for psychotherapy training and supervision: two case examples.
AB - Psychotherapy supervision and training are now widely available online. However,
many supervisors still may be unclear on how online supervision actually works,
or what it actually looks like in practice. In this article, three case examples
of online videoconference-based supervision programs will be described. Partial
transcripts from two online supervision sessions are provided. The benefits and
limitations of online supervision are discussed, including discussion of
supervision process, ethics, privacy, and security.
PMID- 25122988
TI - Clinical supervision in the 21st century: revisiting pressing needs and
impressing possibilities.
AB - What are some of the most pressing needs currently confronting clinical
supervision? In this paper, I give attention to that question. Drawing on two
1990 reviews for comparative purposes, I examine where supervision is now
relative to four areas: (a) supervision training and practice; (b) measurement;
(c) difference and diversity; and (d) research. Lines of advance, pressing needs,
and potential remedies are considered across each area. Effort is made to
accentuate the "robustly international" nature of clinical supervision and its
increasing globalization.
PMID- 25122989
TI - [The medicolegal relevance of benign and malignant coronary artery anomalies].
AB - Isolated coronary anomalies are rare abnormalities that can be divided into
benign and malignant forms. Malignant coronary artery abnormalities generally
present already during infancy or early childhood by causing symptoms or sudden
death. Benign abnormalities often remain asymptomatic because they are
hemodynamically irrelevant. Among the 12,985 autopsies performed at the Institute
of Legal Medicine at the University of Frankfurt (Germany) between 1995 and 2013,
there were eight cases (0.062%) with isolated coronary artery abnormalities. Five
of these cases (0.039%) could be included in our retrospective study. These
involved one deceased female and four deceased male subjects, aged between 2 and
57 years. In three of these cases (aged 6, 9, and 11 years old), the coronary
anomaly was classified as malignant and was recorded as the cause of death.
Benign isolated coronary anomalies are often incidental findings during
autopsies. However, in one of the cases in our study, coronary sclerosis in
precisely the anomalous vessel was found to be the origin of a fatal myocardial
infarction. Malignant isolated coronary artery anomalies attain medicolegal
significance when they remain undetected despite advanced early detection
protocols and cause sudden death in childhood.
PMID- 25122990
TI - [Cause and manner of death in the autopsy material of the Institute of Forensic
Medicine, Justus Liebig University Giessen, from 2002-2006].
AB - A retrospective analysis of the autopsy material of the Institute of Forensic
Medicine, Justus Liebig University Giessen, in the years 2002 to 2006 showed that
the Giessen material is similar to that of comparable studies but contains a
relatively large share of lethal intoxications and cases with a concrete
suspicion of poisoning in which the cause of death was not definitely clarified
by further investigations. On the basis of our own results it is demonstrated
that additional chemical, toxicological and histological examinations are helpful
to determine initially unclear causes of death. In view of the already very low
autopsy rates in Germany it is strange that more detailed diagnostic measures are
often omitted.
PMID- 25122991
TI - [Hans Gross as an archaeologist--the significance of archaeology for
'encyclopedic' criminology].
AB - In some cases, forensics and criminology have to cooperate with disciplines that
usually are counted among the humanities, e.g. with archaeology. This article
examines the significance of this cooperation for the criminological epistemology
at the turn of the 19th century. These methodological considerations are
illustrated by an example: When Hans Gross, who became the founder of the
Austrian School of Criminology later, saw an unusually shaped hill near Feldbach,
a town in southern Styria, he assumed this hill to be a burial mound and informed
the responsible archaeological authorities immediately. Further investigations
showed, however, that this hill was a natural formation. This is an early example
for interdisciplinary cooperation, which proves that both in archaeology and in
criminology a thorough inspection of the site is decisive for further scientific
analysis of the topic of research.
PMID- 25122992
TI - [Intentional poisoning of two wives by their husband?].
AB - The authors report on the death of two women who were married to the same man one
after the other. Exhumation and toxicological investigation of the first wife,
who had died 7 years before, did not produce any conclusive evidence of homicide.
With regard to the circumstances of death of the second wife the husband made
different statements. According to the result of the chemical and toxicological
investigations death was caused by acute intoxication with the beta-blocker
metoprolol. The man was found guilty of killing on request (which is a criminal
offence in Germany) by administering the beta-blocker metoprolol through a
transnasal gastric tube.
PMID- 25122993
TI - [Hand injuries by pyrotechnic articles--case report and reconstructive
experimental investigations].
AB - Injuries caused by explosions of fireworks often involve people's hands. The case
of a young man who suffered severe hand injuries as well as damage to both
eardrums and one eye is described. Reconstructive experimental investigations of
the explosive effect of six different pyrotechnic articles were carried out using
human hands from body donors. With the most powerful firecrackers that used to be
legally available in Germany ("Super-Boller A", "Kanonenschlag") and a self-made
one with 36 g gunpowder only blackening of the skin occurred. Three pyrotechnic
articles not allowed in Germany ("La Bomba", "Color salute" and "Vogelschreck")
caused serious injury to the hand's soft tissue and bones.
PMID- 25122994
TI - [Cranial CT as basis for reconstruction of events and identification of a
weapon].
AB - Radiological findings, especially CT scans, are of great importance in the
reconstruction of events and may also be helpful to identify the weapon used.
This is illustrated by a briefly survived craniocerebral trauma whose origin was
controversially discussed. A 51-year-old man had suffered a severe craniocerebral
trauma in a robbery. The CT scans revealed fractures of the left parietal region,
among them a spider's web fracture, on the cause of which opinions differed (fall
or blow). It was also unclear which of the three confiscated objects (empty wine
bottle, bending iron, wooden hammer) was used for the assault. Evaluation of the
CT findings showed that at least two blows had obviously been inflicted to the
cranial skull. Apart from several injuries of the scalp due to blows, the typical
combination of findings in the occipital region and contre-coup lesions suggested
that the head had also hit the ground due to a fall. The soft tissue injuries may
have been caused by all the three confiscated objects. The bony injuries were
most probably caused by the bending iron, whereas the wooden hammer and the wine
bottle could be ruled out as the causative weapon or were at least highly
improbable.
PMID- 25122995
TI - Effect of chainring ovality on joint power during cycling at different workloads
and cadences.
AB - Non-circular chainrings theoretically enhance cycling performance by increasing
effective chainring diameter and varying crank velocity, but research has failed
to consistently reproduce the benefits in cycling trials. The aim of this study
was (1) to investigate the effect of different chainring shapes on sagittal knee
joint moment and sagittal lower limb joint powers and (2) to investigate whether
alterations are affected by cadence and workload. Fourteen elite cyclists cycled
in six conditions (70, 90 and 110 rpm, each at 180 and 300 W), for 2 min each,
using three chainrings of different ovalities (1.0-1.215). Kinematic data and
pedal forces were collected. For most conditions, only the chainring with the
highest ovality (1.215) was characterised by smaller sagittal knee joint moments,
smaller relative sagittal knee joint power contribution and larger relative
sagittal hip joint power contribution, which suggests a change from maximising
efficiency to maximising power production. Effect sizes increased with higher
cadences, but not with higher workload. This study has application for athletes,
clinicians and sports equipment industry as a non-circular chainring can change
joint-specific power generation and decrease knee joint moment, but certain
ovality seems to be necessary to provoke this effect.
PMID- 25122996
TI - Grip pressure distributions and associated variability in golf: a two-club
comparison.
AB - Teaching and playing professionals offer multiple theories concerning the manner
in which forces should be applied to the handle of the club during the golf
swing. This study extends recent research concerning grip pressures and forces in
golf, with the purpose of exploring the similarities and differences between
force profiles for a 7-iron and driver swung by proficient golfers. A secondary
purpose was to further analyze the way that golfers use grip forces to manipulate
the club. Grip forces were measured on eight low handicap golfers (USGA indexes 0
to 7) swinging their own 7-irons and drivers. In total, lead-hand and trail-hand
grip forces were isolated as well as anatomically specific forces within the
hands. Force profile variability across multiple swings for each golfer and
between golfers characterized consistencies and important differences.
Correlations between 7-iron and driver force profiles characterized force
'signatures.' The data highlight large fluctuations in grip forces during the
swing. Marked differences between participants were observed, involving force
magnitudes and phasing. Dominant forces arose primarily from the lead hand,
specifically the last three fingers. Force profiles were highly repeatable across
swings for a golfer (standard deviations < 7% of total force) and force profile
correlations between 7-iron and driver for a golfer were remarkably high (r2 =
0.86). Notably, within swing force variability was greatest during club
acceleration, but dramatically decreased at impact.
PMID- 25122997
TI - Musculoskeletal loading during the round-off in female gymnastics: the effect of
hand position.
AB - Chronic elbow injuries from tumbling in female gymnastics present a serious
problem for performers. This research examined how the biomechanical
characteristics of impact loading and elbow kinematics and kinetics change as a
function of technique selection. Seven international-level female gymnasts
performed 10 trials of the round-off from a hurdle step to flic-flac with
'parallel' and 'T-shape' hand positions. Synchronized kinematic (3D-automated
motion analysis system; 247 Hz) and kinetic (two force plates; 1,235 Hz) data
were collected for each trial. Wilcoxon non-parametric test and effect-size
statistics determined differences between the hand positions examined in this
study. Significant differences (p < 0.05) and large effect sizes (ES > 0.8) were
observed for peak vertical ground reaction force (GRF), anterior-posterior GRF,
resultant GRF, loading rates of these forces and elbow joint angles, and internal
moments of force in sagittal, transverse, and frontal planes. In conclusion, the
T-shape hand position reduces vertical, anterior-posterior, and resultant contact
forces and has a decreased loading rate indicating a safer technique for the
round-off. Significant differences observed in joint elbow moments highlighted
that the T-shape position may prevent overloading of the joint complex and
consequently reduce the potential for elbow injury.
PMID- 25122998
TI - An analysis of two styles of arm action in the vertical countermovement jump.
AB - The aim of this study was to determine the effect of two arm swing techniques,
the simultaneous arm swing and the early arm swing, on vertical countermovement
jump performance and on the contribution of the arms to vertical movement at the
centre of mass (CM) during the propulsion phase. Participants were 28 athletes
practicing sports in which the vertical jump constitutes a basic ability. Ground
reaction forces were recorded by a force platform and the sagittal plane motion
was recorded by a video camera. Although at take-off the vertical velocity (2.7
+/- 0.2m/s for simultaneous technique vs. 2.8 +/- 0.2m/s for early technique; p =
0.040) and position (1.18 +/- 0.06m for simultaneous vs. 1.17 +/- 0.05m for
early; p = 0.033) of the CM were significantly different, no difference was
observed in jump height (1.56 +/- 0.01m in both techniques). The arm action
differed during the initial and final propulsion phases in both styles but the
accumulated vertical contribution was similar. The practical implication in
sports is that the use of the arm-swing technique to reach the maximum jump
height should be determined by tactical demands instead of the technical
execution of the arms.
PMID- 25122999
TI - Comparison of support leg kinetics between side-step and cross-step cutting
techniques.
AB - The purpose of this study was to investigate differences in the support leg joint
moment and moment power between side-step (SS) and cross-step (CS) cutting
techniques with a prescribed 90 degrees cutting angle. Ground reaction forces
(1,000Hz) and three-dimensional kinematics (250Hz) of SS and CS cutting
techniques were collected from 20 male college athletes. Normalised peak knee
extension moment was larger in the SS technique than in the CS technique (0.40 +/
0.10 in SS; 0.26 +/- 0.08 in CS). In the SS technique, the knee extensors (-0.10
+/- 0.06 in SS; -0.02 +/- 0.04 in CS) and ankle plantarflexors (-0.12 +/- 0.05 in
SS; -0.07 +/- 0.03 in CS) did significantly more negative work (normalised). The
direction change angle (40.5 +/- 8.7 degrees in SS; 33.0 +/- 6.8 degrees in CS)
and the decrease in horizontal velocity of the centre of mass (-0.63 +/- 0.23 m/s
in SS; -0.31 +/- 0.23 m/s in CS) were significantly larger in the SS technique.
These results suggest that the SS technique is an effective means of changing
running direction at the expense of velocity of the centre of mass and that the
CS technique is better for minimising the reduction in horizontal velocity of the
centre of mass.
PMID- 25123000
TI - Is starting with the feet out of the water faster in backstroke swimming?
AB - This study aimed to determine if starting with the feet above the water (FAW) in
male backstroke swimming resulted in faster start times (15-m time) than when the
feet were underwater (FUW). It was hypothesised that setting higher on the wall
would generate increased horizontal force and velocity, resulting in quicker
starts. Twelve high-level male backstrokers performed three trials of the FAW and
FUW techniques. A biomechanical swimming testing system comprising one force
plate (1,000 Hz), four lateral-view (100Hz), and five overhead (50Hz) video
cameras captured the swimmers' performance. Data for each participant's fastest
trial for each technique were collated, grouped, and statistically analysed.
Analysis included Wilcoxon, Spearman Rho correlation, and regression analysis.
Wilcoxon results revealed a significantly faster start time for the FAW technique
(p < 0.01). Peak horizontal force was significantly smaller for FAW (p = 0.02),
while take-off horizontal velocity was significantly greater (p = 0.01).
Regression analysis indicated take-off horizontal velocity to be a good predictor
of start time for both techniques, and the horizontal displacement of the centre
of mass for the FAW start.
PMID- 25123001
TI - Scapulothoracic kinematics during tennis forehand drive.
AB - Scapular dyskinesis is recognized as an abnormality in the kinetic chain; yet,
there has been little research quantifying scapular motion during sport tasks.
Tennis forehand drives of eight highly skilled tennis players were studied to
assess the scapulothoracic kinematics and evaluate repeatability using video
based motion analysis. Scapulothoracic downward/upward rotation,
posterior/anterior tilt, and internal/external rotation were computed using an
acromial marker cluster. On average, the upward rotation, anterior tilt, and
internal rotation varied from 1 degrees to 26 degrees, from 7 degrees to 32
degrees, and from 42 degrees to 100 degrees, respectively, during the tennis
forehand drive. During the backswing and forward swing phases of the forehand
stroke, small changes were observed for the three scapular angle values, while
all angles increased rapidly during the follow-through phase. This suggests that
the tennis forehand drive may contribute to scapula dyskinesis, mainly due to the
great amplitude in scapulothoracic anterior tilt and internal rotation observed
during the follow-through phase. Knowledge of normal scapula motion during sport
tasks performed at high velocity could improve the understanding of various sport
specific adaptations and pathologies.
PMID- 25123002
TI - Unsteady flow phenomena in human undulatory swimming: a numerical approach.
AB - The undulatory underwater sequence is one of the most important phases in
competitive swimming. An understanding of the recurrent vortex dynamics around
the human body and their generation could therefore be used to improve swimming
techniques. In order to produce a dynamic model, we applied human joint
kinematics to three-dimensional (3D) body scans of a female swimmer. The flow
around this dynamic model was then calculated using computational fluid dynamics
with the aid of moving 3D meshes. Evaluation of the numerical results delivered
by the various motion cycles identified characteristic vortex structures for each
of the cycles, which exhibited increasing intensity and drag influence. At
maximum thrust, drag forces appear to be 12 times higher than those of a passive
gliding swimmer. As far as we know, this is the first disclosure of vortex rings
merging into vortex tubes in the wake after vortex recapturing. All unsteady
structures were visualized using a modified Q-criterion also incorporated into
our methods. At the very least, our approach is likely to be suited to further
studies examining swimmers engaging in undulatory swimming during training or
competition.
PMID- 25123003
TI - Comparisons of the latching on between newborns with tongue-tie and normal
newborns.
AB - BACKGROUND: Breastfeeding is recommended as the exclusive feeding for the first
six months of the newborns life. Difficulty in latching and breastfeeding
resulting from tongue-tie are believed to be a problem. OBJECTIVE: To compare the
latching on between newborns with tongue-tie (ankyloglossia) and normal newborns.
MATERIAL AND METHOD: The subjects were 833 normal, postpartum women who delivered
without complications at HRH Princess Maha Chakri Sririndhorn Medical Center in
Nakhon Nayok Province between January and June 2013. Their newborns oral
cavities' were checked for tongue-tie screening and diagnoses using Kotlow's
criteria. Latch scores were used for latch-on assessment at the second day
postpartum. Demographic data and latch scores were collected and analyzed by the
t-test, Chi-square test, Odds ratio with 95% confidence interval and One-way of
ANOVA test. RESULTS: The data shows that the incidence of tongue-tie was 13.4%
(6.2% with mild tongue-tie, 5.5% with moderate tongue-tie, and 1.7% with severe
tongue-tie). The mean of latch scores in the tongue-tied groups were
significantly lower than that in the normal group, especially in the moderate and
severe tongue-tie subgroups. The odds ratios for latch scores were < or = 8
compared between the moderate and severe tongue-tied subgroups and the score in
the normal and mild tongue-tied subgroups was 1.4. CONCLUSION: The latch scores
in tongue-tied newborns were significantly lower than those in normal newborns.
PMID- 25123004
TI - Management and clinical outcomes of endometrial hyperplasia during a 13-year
period in Songklanagarind Hospital.
AB - BACKGROUND: Endometrial hyperplasia has long been considered a precursor of
endometrial cancer but there is no consensus regarding its management. OBJECTIVE:
To identify management practices and evaluate outcomes of treatments for women
diagnosed with endometrial hyperplasia (EH). MATERIAL AND METHOD: The medical
records of endometrial hyperplasia at Songklanagarind Hospital between January
2000 and December 2012 were retrospectively reviewed. RESULTS: Two hundred ninety
seven patients were diagnosed with endometrial hyperplasia during the study
period. Four patients who did not come for treatment and could not be contacted
were excluded Therefore, 293 patients were included in the study. Simple
hyperplasia (SH) was the most common diagnosis accounting for 79.2% of all cases,
followed by complex hyperplasia (CH) 13.0%, complex atypical hyperplasia (CAH)
5.8%, and simple atypical hyperplasia (SAH) 2.0%. Seventy-eight percent (18/23)
of the patients with atypical endometrial hyperplasia were treated by
hysterectomy compared with 9.6% (26/270) of patients without atypia. Of the
patients diagnosed with atypical EH, 30.4% (7/23) were associated with
endometrial carcinoma. Overall, 6% (12/201) of the women who had initial non
hysterectomy management and had additional tissue taken to assess response, had
persistent disease, and 1% (2/201) had progressive disease. Eleven patients
(5.9%), who had an initial complete regression during the non-hysterectomy
management, experienced a recurrence to EH and 2.1% (4/187) were found to have
recurrence to endometrial cancer CONCLUSION: The majority of patients with
atypical hyperplasia were managed by initial hysterectomy. The high risk of
concomitant endometrial cancer supports this choice of treatment. In the non
atypical EH, the initial non-hysterectomy management was common but EH recurrence
and progression to endometrial cancer after the initial regression occurs often.
Therefore, long-term follow-up should be advised.
PMID- 25123005
TI - Nomogram of placental thickness, placental volume and placental vascular indices
in healthy pregnant women between 12 and 20 weeks of gestation.
AB - OBJECTIVE: To generate the nomogram of placental thickness, volume, and vascular
indices in healthy pregnant women between 12 to 20 weeks of gestation. MATERIAL
AND METHOD: An experimental cross sectional study of pregnant women, which were
categorized into nine groups according to their gestational age ranging from 12
to 20 weeks of gestation, was done. Placental parameters that included placental
thickness, volume, and vascular indices were measured using a Voluson E8
ultrasound machine. The measurements were correlated with gestational age.
RESULTS: Two hundred ninety four subject were included in this study. The study
indicated that the placental thickness and volume significantly increased with
gestational age (r = 0.481, p < 0.001 and r = 0.837, p < 0.001). The correlation
between the placental volume and gestational age can be formulated according to
this equation: Placental volume (cm3) = e7.584-42.45(1/GA); R2 = 0.76.
Nonetheless, there is a very low correlation between the vascularization index
(VI), vascularization flow index (VFI), and the gestational age (r = 0.162, p =
0.005 and r = 0.158, p = 0.007). The flow index (FI) was shown to have no
correlation with gestational age (r(p) = -0.067, p = 0.254). CONCLUSION: From the
present study, the placental thickness and placental volume significantly
increased with gestational age. The VI and VFI showed poor correlation with
gestational age while the FI had no correlation with the gestational age.
PMID- 25123006
TI - Radiation, chemotherapy or combined modality therapy in adjuvant treatment for
stage III endometrial carcinoma in lower southern Thailand: disease recurrence
and overall survival.
AB - OBJECTIVE: To survey disease-free survival (DFS) and overall survival (OS) of
patients with stage III endometrial carcinoma treated with post-operative
radiation and/or chemotherapy MATERIAL AND METHOD: The medical records of
patients with surgical stage III endometrial carcinoma, and receiving adjuvant
treatment between January 2003 and December 2012 were reviewed DFS and OS were
analyzed using the Kaplan-Meier method and Cox proportional hazards model.
RESULTS: Of the 54 eligible patients, 61% underwent radiation, 19% chemotherapy,
and 20% chemotherapy with radiation. The median DFS was 36.7 months. The 3-year
DFS and OS was 51.9% (95% CI 36.3-74.1%) and 70.6% (95% CI 57.4-86.8%),
respectively. There was no significant difference in DFS and OS among treatment
groups. Cox regression analysis showed grade 2-3 tumors and menopause were
associated with poor DFS and OS. CONCLUSION: The DFS and OS in stage III
endometrial carcinoma receiving postoperative adjuvant therapy were quite good
and were not different among radiation therapy, chemotherapy, and combined
treatment groups. The multi-center randomized prospective study was needed to
determine the standard modality.
PMID- 25123007
TI - Burden of adult pneumonia in Thailand: a nationwide hospital admission data 2010.
AB - OBJECTIVE: To quantify the admission mortality, pathogens,factors related to
mortality, length of hospital stay, and healthcare costs in adult hospitalized
pneumonia in Thailand MATERIAL AND METHOD: The data on hospitalized pneumonia for
the 2010 fiscal year extracted from the three main health insurance coverage
schemes in Thailand (the Social Security System (SSS), the Medical Welfare System
(MWS), and the Civil Servant Medical Benefit System (CSMBS)) were analyzed
RESULTS: Adult hospitalized pneumonia admissions numbered 136,696, with mortality
rate 9.63%. The mortality increased with increasing age, 15.49% for age > 80
years. Influenza virus was the major etiology for 19 to 25 years old (49.30%)
with low mortality (1-2%). S. pneumoniae and typical pathogens were found in
every age group. The mortality rate for S. pneumoniae increased with age, viz.
0%, 1.96%, 5.56%, 7.02%, 6.98%, and 24.24% for 19 to 25, 26 to 40, 41 to 60, 61
to 70, 71 to 80, and 81+ years old. The mortality rate from C. pneumonia was
about 10% and high among the younger age group. Gram-negative bacilli and
Staphylococcus caused high mortality (about 20 to 35%), especially in the older
age group. The major risk factors for increasing mortality were: elderly (OR
3.46, 95% CI 3.27-3.77), alcoholic liver disease (OR 3.26, 95% CI 2.85-3.72),
cirrhosis (OR 3.45, 95% CI 2.93-4.08), heart disease (OR 2.47, 95% CI 2.38-2.56),
ischemic heart disease (OR 2.21, 95% CI 2.07-2.36), renal failure (OR 5.26, 95%
CI 5.07-5.49), and cerebrovascular disease (OR 3.62, 95% CI 3.43-3.82). The
median length of hospital stay was four days (IQR, 3-7 days) and the median cost
of treatment per admission was US$ 256.63 (IQR, US$ 147.81-531.21). Complications
such as acute respiratory failure, acute respiratory distress syndrome (ARDS),
septicemia, shock, and acute renal failure made hospital stays two to three days
longer and costs three to seven times higher than no complications. CONCLUSION:
The mortality from pneumonia among the elderly was high, especially for those
over 80 and with multiple medical co-morbidities.
PMID- 25123008
TI - The association between bioimpedance analysis and quality of life in pre-dialysis
stage 5 chronic kidney disease, hemodialysis and peritoneal dialysis patients.
AB - BACKGROUND: Protein-energy wasting is a significant problem in End stage renal
disease (ESRD) patients. Furthermore, it compromises the patient's Quality of
life (QOL). Multifrequency Bioimpedance Spectroscopy (BIS) is a validated method
to assess body composition in dialysis patients. There has been no data on the
relationship between body composition and QOL in ESRD patients who were treated
with different modalities. OBJECTIVE: To explore the association between body
composition as assessed by BIS and QOL in ESRD patients who received different
treatment modalities. MATERIAL AND METHOD: The present study is a cross
sectional, descriptive analytic study of the association between QOL and BIS in
ESRD patients in Burapha University, Chonburi, Thailand. QOL was assessed by
WHOQOL-BREF questionnaire, body composition was measured by BIS technique. The
difference between groups was tested by one-way ANOVA test, relationship between
groups was tested with Pearson correlation test. RESULTS: Eighteen predialysis
CKD5, 26 peritoneal dialysis (PD), and 34 hemodialysis (HD) patients were
included in the present study. All PD patients had weekly Kt/V > or = 1.7 per
week and all HD patients had weekly Kt/V > or = 3.6 per week. There were no
statistically difference in baseline characteristics including Charlson
comorbidity index, dietary intake, BMI, and blood pressure between groups. Mean
QOL scores in each group were in the middle range and not significantly
difference. PD patients had more over hydration when compare to HD patients
(16.18 +/- 11.24 vs. 2.36 +/- 11.07 %OH/ECW p < 0.0001). There were inversed
correlation between overhydration and physical health in HD patients (r = -0.372,
p = 0.033) but not in PD and CKD5 patients. CKD5 patients had more lean tissue
index (LTI) than PD and HD patients (LTI = 14.34 +/- 3.13, 12.26 +/- 3.65, 11.48
+/- 3.48 kg/m2 respectively, p = 0.023). There were correlation between LTI and
overall QOL in CKD5 (r = 0.690, p = 0.002) and PD patients (r = 0.498, p =
0.010). In HD patients, LTI was associated with better physical health (r =
0.464, p = 0.007). CONCLUSION: QOL in predialysis-CKD5, PD and HD patients were
not statistically different. HD patients had better volume control than PD
patients. Higher LTI were associated with better QOL in ESRD patients.
PMID- 25123009
TI - The associations of SEA-alpha thalassemia 1, XmnI-Ggamma polymorphism and beta
globin gene mutations with the clinical severity of beta-thalassemia syndrome in
northern Thailand.
AB - BACKGROUND: At least three genetic factors including beta-thalassemia mutations,
alpha-thalassemia, and XmnI-Ggamma polymorphism were shown to modify clinical
symptoms in beta-thalassemia disease. OBJECTIVE: To determine associations of
beta-thalassemia mutations, SEA-alpha thalassemia 1, and XmnI-Ggamma
polymorphism, and clinical severity of beta-thalassemia in northern Thailand.
MATERIAL AND METHOD: Thirty-two beta-thalassemia major and 28 beta-thalassemia
intermedia attending the Thalassemia Clinic at Maharaj Nakorn Chiang Mai
Hospital, Chiang Mai, Thailand were recruited The beta-globin gene mutations and
SEA-alpha thalassemia 1 were determined by MS-PCR and Gap-PCR, respectively. The
XmnI-Ggamma polymorphism was identified by RFLP analysis. Odds ratio was
calculated to evaluate the associations of these three genetic factors and
clinical symptoms. RESULTS: Eight beta-globin gene mutations (both beta0 and
beta+) were found Twenty-nine point one percent of the patients had at least one
XmnI-Ggamma site (XmnI-Ggamma: +) and 4.1% of the patients were heterozygote for
the SEA-alpha thalassemia 1. The beta-globin gene mutations showed maximal impact
and the XmnI-Ggamma polymorphism had minimal influence on clinical severity in
this cohort. The SEA-alpha thalassemia 1 had the least effect on the clinical
severity due to its low prevalence in these patients. CONCLUSION: Although these
three genetic factors play roles in modifying clinical symptoms of beta
thalassemia, the beta-thalassemia mutations should be considered first, followed
respectively by the XmnI-Ggamma polymorphism and the SEA-alpha thalassemia 1, in
management and prenatal diagnosis of beta-thalassemia in northern Thailand.
PMID- 25123010
TI - Validation of the Thai version of the questionnaire for identifying subjects with
potential rheumatic diseases.
AB - OBJECTIVE: To translate and evaluate the diagnostic property and the feasibility
of the Thai version of the questionnaire for identifying subjects with potential
rheumatic diseases. MATERIAL AND METHOD: The original screening questionnaires by
Liang MH et al were translated and modified from the English version to the Thai
version. The Thai version of the questionnaire was administered to 450 subjects.
RESULTS: Two hundred and twenty-five patients who fulfilled standard diagnostic
criteria of each rheumatic disease and 225 healthy subjects were consecutively
recruited. A positive response to one or more questions of the questionnaire gave
a sensitivity (95% confidence interval or CI), specificity (95% CI), positive,
and negative likelihood ratios of 94% (90-97), 73% (67-79), 3.48, and 0.08,
respectively. The accuracy of test was 93%. Median time-to-complete questionnaire
was three minutes (range 0.5-15). Most ofthem (950%) completed questionnaires by
themselves. However 12% of the questionnaires had missing items. False positive
was prevalent in women, young age, high-educated individuals, and government
officers. CONCLUSION: The Thai version of the screening questionnaire is valid
and easy to use for identifying subjects with potential rheumatic diseases. It is
suitable to use as a screening tool in primary care setting or epidemiologic
research.
PMID- 25123011
TI - Patency of vascular accesses for Thai hemodialysis patients.
AB - OBJECTIVE: Vascular access for hemodialysis is the mode of renal replacement
therapy for chronic renal failure patients. The present study reports patency
rates of arteriovenous fistula (AVF) and graft (AVG). MATERIAL AND METHOD:
Between July 2008 and June 2011, 336 vascular accesses were performed in 293
patients in Department of Surgery, Faculty of Medicine, Khon Kaen University. The
patient was follow until June 2012. A retrospective review was conduct to analyze
patency rate. RESULTS: Two hundred ninety three patients underwent 286 AVFs and
50 AVGs. Patency rate was analyzed with the Kaplan-Meier method. Primary patency
rate of AVF at one, two, and three-year was 78.69%, 70.43%, and 60.72%,
respectively Assisted primary patency of AVF at one, two, and three-year was
88.24%, 75.63%, and 40.34%, respectively. Secondary patency rate of AVF at one
and two-year was 71.46% and 71.46%, respectively. Primary patency rate of AVG at
one, two, and three-year was 63.94%, 43.93%, and 36.60%, respectively. Assisted
primary patency of AVG at one-year was 100%. Secondary patency rate of AVG at one
year was 46.30%. Graft infection was the major complication ofAVG (12%).
CONCLUSION: The authors' results of vascular access surgery were comparable to
results from a review of literature.
PMID- 25123012
TI - Comparative study of femoral sizing between intraoperative measurement and CT
based PSI in total knee arthroplasty.
AB - BACKGROUND: Appropriate femoral sizing in total knee arthroplasty (TKA) is an
important factor for flexion. An oversized femoral component will decrease
flexion gap and postoperative flexion. By using custom cutting blocks technique
with computed tomography (CT) imaging to design cutting blocks will help
determine sizing of each patient. The differences of femoral sizing between
intraoperative measurement and custom cutting blocks technique are still
questionable. OBJECTIVE: To compare femoral component sizing between custom
cutting blocks technique and conventional technique. MATERIAL AND METHOD:
Retrospective cross-sectional study was collected from 2,321 patients underwent
primary TKA with the same prosthesis design in Bangkok between January 2012 and
December 2012. The population was separated into three groups, group A, 2,053
patients operated by orthopedic surgeons in Bangkok by conventional instrument
femoral sizing, group B, 218 patients operated by senior experienced arthroplasty
surgeon (Chotanaphuti T) at Phramongkutklao Hospital using the same measurement
technique as group A, and group C, 50 patients operated by Chotanaphuti T using
custom cutting blocks technique for femoral sizing. The femoral component sizes
were assigned from small to large size as number 1 to 6. Chi-square test and
Fisher's exact test was used to determine the significant differences between
amount of patients of each group. RESULTS: In group A, femoral components were
selected in size 1 (n = 157; 8%), 2 (n = 576; 28%), 3 (n = 737; 36%), 4 (n = 431;
21%), 5 (n = 144; 7%), and 6 (n = 8; 0.4%) respectively. In group B, femoral
components were selected in size 1 (n = 31; 14%), 2 (n = 55; 25%), 3 (n = 64;
29%), 4 (n = 31; 140%), 5 (n = 37; 180%), and 6 (n = 0; 0%) respectively. In
group C, femoral components were selected in size 1 (n = 7; 14%), 2 (n = 19;
38%), 3 (n = 11; 220%), 4 (n = 12; 24%), 5 (n = 1; 20%), and 6 (n = 0; 0%)
respectively. The most chosen size of group A and B were No. 3, but for group C
was No. 2, which was smaller than the first two group by one size. There were
statistical difference in group A versus group B (p < 0.0001), and group B versus
group C (p = 0. 009), but not difference in group A versus group C (p = 0. 096).
CONCLUSION: Custom cutting blocks technique chooses a femoral component closer to
knee anatomy of the patients and smaller than intraoperative technique. There are
several possible causes, which include variable of level or sagittal angle error
of distal femoral bone cut.
PMID- 25123013
TI - The sensory restoration in radial nerve injury using the first branch of dorsal
ulnar cutaneous nerve--a cadaveric study for the feasibility of procedure and
case demonstration.
AB - OBJECTIVE: To demonstrate the new sensory restoration technique in radial nerve
injury using the first branch of dorsal ulnar cutaneous nerve as the donor
sensory nerve. MATERIAL AND METHOD: Forty formalin-preserved cadavers (18 males
and 22 females) were used as the subjects of the present study. The localization
of the origin of first branch of dorsal ulnar cutaneous nerve was performed. The
measurement was done to determine the origin of this nerve in relation to the tip
of ulnar styloid. The simulated transfer was done. The length of the superficial
radial nerve that had to be cut was determined. The measurement was done by two
observers to determine the reliability of measurement. RESULTS: The mean
horizontal distance (X) to the origin of first branch of dorsal ulnar cutaneous
nerve measured from the tip of ulnar styloid on the right and left side were 5.22
mm and 6.51 mm respectively. The mean vertical distance (Y) to the origin of
first branch of dorsal ulnar cutaneous nerve measured from the tip of ulnar
styloid on the right and left side were -7.72 mm and -4.37 mm respectively. The
mean length of superficial radial nerve that had to be cut to allow tension free
anastomosis, measured from the tip of radial styloid on the right and left side
were 68.21 mm and 65.92 mm respectively. The estimated average size of the
transferred branch of ulnar cutaneous nerve was about 70% of the size of
superficial radial nerve. CONCLUSION: The sensory restoration in radial nerve
injury using sensory nerve transfer from the first branch of dorsal ulnar
cutaneous nerve was technically feasible regarding to the comparable size between
two nerves and anatomic consistency of the first branch of dorsal ulnar cutaneous
nerve.
PMID- 25123014
TI - CT perfusion in predicting treatment response of nasopharyngeal carcinoma.
AB - BACKGROUND: Direct nasopharyngoscope with biopsy is the gold standard for
assessing tumor response of nasopharyngeal carcinoma (NPC). It is invasive with
risk of hemorrhage or infection. OBJECTIVE: Explore the usefulness of pre
treatment CTperfusion (CTP) and clarify the parameters in predicting the
treatment response. MATERIAL AND METHOD: Twelve patients with histologically
proven NPC who underwent pretreatment contrast enhanced CT (CECT) and CTP with
parameters (blood flow (BF), blood volume (BV) and permeability), followed by
CECT at three months after complete concurrent chemo-radiotherapy or radiotherapy
were included in this prospective, cross-sectional study. Pre- and post-treatment
primary tumor volumes based on free hand drawn region encompassing the entire
primary tumor were measured and compared The response to therapy was also
assessed by RECIST guideline version 1.1, based on sum of the diameters of
longest diameter for primary tumor and minimal transverse diameter for nodal
lesions for all target lesions on the pre- and post-treatment imaging, and
classified into "Non-response" group and "Complete response" group. Statistical
analysis was performed using Pearson 's correlation coefficients and Mann-Whitney
U test. RESULTS: Ten and two patients (83.3%, 16.7%) belonged to "Complete
response" and "Non-response "groups respectively. Elevated permeability, BF and
BV had a following trend of positive correlation with degree of primary tumor
volume reduction without statistical significance. The values ofpermeability, BFE
and BV had a trend to be higher in "Complete response" group compared with "Non
response" group (p = 0.053, 0.390 and 0.519 respectively). The permeability had
the highest predictive value with an area under the ROC curve of 0.95 and cutoff
value of 45 ml/100 g/min (sensitivity, 100%; specificity, 90%). CONCLUSION: Pre
treatment CTP can be useful non-invasive tool in predicting treatment response of
NPC. Permeability is the excellent parameter used to differentiate between
complete and non-response groups.
PMID- 25123015
TI - Efficiency comparison of three methods for extracting genomic DNA of the
pathogenic oomycete Pythium insidiosum.
AB - BACKGROUND: The fungus-like organism Pythium insidiosum is the causative agent of
a life-threatening tropical infectious disease, pythiosis, which has high rates
of morbidity and mortality. A lack of reliable diagnostic tools and effective
treatments for pythiosis presents a major challenge to healthcare professionals.
Unfortunately, surgical removal of infected organs remains the default treatment
for pythiosis. P. insidiosum is an understudied organism. In-depth study of the
pathogen at the molecular level could lead to better means of infection control
High quality genomic DNA (gDNA) is needed for molecular biology-based research
and application development, such as: PCR-assisted diagnosis, population studies,
phylogenetic analysis, and molecular genetics assays. OBJECTIVE: To evaluate
quality and quantity of the P. insidiosum gDNA extracted by three separate
protocols intended for fungal gDNA preparation. MATERIAL AND METHOD: Seven P.
insidiosum isolates were subjected to gDNA extraction by using conventional
extraction, rapid-extraction, and salt-extraction protocols. RESULTS: The
conventional protocol offered the best gDNA in terms of quality and quantity, and
could be scaled up. The rapid-extraction protocol had a short turnaround time,
but the quality and quantity of the gDNA obtained were limited. The salt
extraction protocol was simple, rapid, and efficient, making it appealing for
high throughput preparation of small-scale gDNA samples. CONCLUSION: Compared to
rapid-extraction protocol, both conventional-extraction and salt-extraction
protocols provided a better quality and quantity of gDNA, suitable for molecular
studies of P. insidiosum. In contrast to the other two methods, the salt
extraction protocol does not require the use of hazardous and expensive materials
such as phenol, chloroform, or liquid nitrogen.
PMID- 25123016
TI - Effectiveness of olanzapine for the treatment of breakthrough chemotherapy
induced nausea and vomiting.
AB - OBJECTIVE: To evaluate safety and efficacy of olanzapine for breakthrough emesis
in addition to standard antiemetic regimen in cancer patients receiving highly
emetogenic chemotherapy. MATERIAL AND METHOD: A phase II prospective open label
clinical trial was conducted in tertiary care based hospital. Forty-six cancer
patients diagnosed with solid tumors were enrolled to receive at least one cycle
of highly emetogenic chemotherapy (HEC) every two to four weeks. Each patient was
provided standard antiemetic consisting of the generic form of ondansetron plus
corticosteroids and metoclopramide according to clinical practice guideline.
Olanzapine was administered as 5 mg orally every 12 hours for two doses in
patients experiencing breakthrough emesis for at least one episode despite
standard prevention. The efficacy and tolerability were evaluated every six hours
for 24 hours (utilizing Index of Nausea, Vomiting and Retching: INVR tool).
RESULTS: Of 46 evaluable patients receiving HEC and additional olanzapine between
September 2009 and July 2010, the complete response of breakthrough emesis,
retching, and nausea control among patients were 60.9%, 71.7%, and 50.0%,
respectively. Adverse events reported were mild and tolerable including
dizziness, fatigue, and dyspepsia. CONCLUSION: Olanzapine is considered to be
safe and effective treatment of breakthrough vomiting in cancer patients
undergoing highly emetogenic chemotherapy in the present study.
PMID- 25123017
TI - Co-existence of porokeratosis variants concurrent with Bowen's disease: two rare
cases report.
AB - Coexisting variants of porokeratosis rarely occurs. Disseminated superficial
porokeratosis (DSP) is characterized by multiple uniform small annular papules
distributed all over body. DSP commonly coexist with linear porokeratosis (LP),
but it is uncommon for DSP to coexist with porokeratosis of Mibelli (PM). PM
presents with central atrophic erythematous plaques and thread-like elevated
border. It occurs mainly on extremities. Although malignant transformation can be
found in the porokeratosis, there is still no report case of coexisting variants
of porokeratosis concurrent with Bowen's disease. The clinical and
histopathologic finding of rare coexisting variants of porokeratosis (PM and DSP)
concurrent with squamous dysplasia is described.
PMID- 25123019
TI - Itching for answers: how histamine relaxes lymphatic vessels.
AB - In the current issue of Microcirculation, studies by Kurtz et al. and
Nizamutdinova et al. together provide new evidence supporting a role for
histamine as an endothelial-derived molecule that inhibits lymphatic muscle
contraction. In particular, Nizamutdinova et al. show that the effects of flow
induced shear stress on lymphatic endothelium are mediated by both nitric oxide
and histamine, since only blockade of both prevents contraction strength and
frequency from being altered by flow. Separately, Kurtz et al. used confocal
microscopy to determine a preferential expression of histamine receptors on the
lymphatic endothelium and demonstrated that histamine applied to spontaneously
contracting collecting lymphatics inhibits contractions. Previous studies
disagreed on whether histamine stimulates or inhibits lymphatic contractions, but
also used differing concentrations, species, and preparations. Together these new
reports shed light on how histamine acts within the lymphatic vasculature, but
also raise important questions about the cell type on which histamine exerts its
effects and the signaling pathways involved. This editorial briefly discusses the
contribution of each study and its relevance to lymphatic biology.
PMID- 25123020
TI - Call for papers: development of action mirroring: submissions due 1 February
2015.
PMID- 25123021
TI - Is increased choroidal thickness associated with primary angle closure?
PMID- 25123018
TI - Chronic loss of noradrenergic tone produces beta-arrestin2-mediated cocaine
hypersensitivity and alters cellular D2 responses in the nucleus accumbens.
AB - Cocaine blocks plasma membrane monoamine transporters and increases extracellular
levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT). The addictive
properties of cocaine are mediated primarily by DA, while NE and 5-HT play
modulatory roles. Chronic inhibition of dopamine beta-hydroxylase (DBH), which
converts DA to NE, increases the aversive effects of cocaine and reduces cocaine
use in humans, and produces behavioral hypersensitivity to cocaine and D2 agonism
in rodents, but the underlying mechanism is unknown. We found a decrease in beta
arrestin2 (betaArr2) in the nucleus accumbens (NAc) following chronic genetic or
pharmacological DBH inhibition, and overexpression of betaArr2 in the NAc
normalized cocaine-induced locomotion in DBH knockout (Dbh -/-) mice. The D2/3
agonist quinpirole decreased excitability in NAc medium spiny neurons (MSNs) from
control, but not Dbh -/- animals, where instead there was a trend for an
excitatory effect. The Galphai inhibitor NF023 abolished the quinpirole-induced
decrease in excitability in control MSNs, but had no effect in Dbh -/- MSNs,
whereas the Galphas inhibitor NF449 restored the ability of quinpirole to
decrease excitability in Dbh -/- MSNs, but had no effect in control MSNs. These
results suggest that chronic loss of noradrenergic tone alters behavioral
responses to cocaine via decreases in betaArr2 and cellular responses to D2/D3
activation, potentially via changes in D2-like receptor G-protein coupling in NAc
MSNs.
PMID- 25123023
TI - Fumarates, a new treatment option for therapy-resistant hidradenitis suppurativa:
a prospective open-label pilot study.
PMID- 25123022
TI - Targets for parathyroid hormone in secondary hyperparathyroidism: is a "one-size
fits-all" approach appropriate? A prospective incident cohort study.
AB - BACKGROUND: Recommendations for secondary hyperparathyroidism (SHPT) consider
that a "one-size-fits-all" target enables efficacy of care. In routine clinical
practice, SHPT continues to pose diagnosis and treatment challenges. One
hypothesis that could explain these difficulties is that dialysis population with
SHPT is not homogeneous. METHODS: EPHEYL is a prospective, multicenter,
pharmacoepidemiological study including chronic dialysis patients (>= 3 months)
with newly SHPT diagnosis, i.e. parathyroid hormone (PTH) >= 500 ng/L for the
first time, or initiation of cinacalcet, or parathyroidectomy. Multiple
correspondence analysis and ascendant hierarchical clustering on clinico
biological (symptoms, PTH, plasma phosphorus and alkaline phosphatase) and
treatment of SHPT (cinacalcet, vitamin D, calcium, or calcium-free calcic
phosphate binder) were performed to identify distinct phenotypes. RESULTS: 305
patients (261 with incident PTH >= 500 ng/L; 44 with cinacalcet initiation) were
included. Their mean age was 67 +/- 15 years, and 60% were men, 92% on
hemodialysis and 8% on peritoneal dialysis. Four subgroups of SHPT patients were
identified: 1/ "intermediate" phenotype with hyperphosphatemia without
hypocalcemia (n = 113); 2/ younger patients with severe comorbidities,
hyperphosphatemia and hypocalcemia, despite SHPT multiple medical treatments,
suggesting poor adherence (n = 73); 3/ elderly patients with few cardiovascular
comorbidities, controlled phospho-calcium balance, higher PTH, and few treatments
(n = 75); 4/ patients who initiated cinacalcet (n = 43). The quality criterion of
the model had a cut-off of 14 (>2), suggesting a relevant classification.
CONCLUSION: In real life, dialysis patients with newly diagnosed SHPT constitute
a very heterogeneous population. A "one-size-fits-all" target approach is
probably not appropriate. Therapeutic management needs to be adjusted to the 4
different phenotypes.
PMID- 25123024
TI - Continuous and simultaneous estimation of finger kinematics using inputs from an
EMG-to-muscle activation model.
AB - BACKGROUND: Surface electromyography (EMG) signals are often used in many robot
and rehabilitation applications because these reflect motor intentions of users
very well. However, very few studies have focused on the accurate and
proportional control of the human hand using EMG signals. Many have focused on
discrete gesture classification and some have encountered inherent problems such
as electro-mechanical delays (EMD). Here, we present a new method for estimating
simultaneous and multiple finger kinematics from multi-channel surface EMG
signals. METHOD: In this study, surface EMG signals from the forearm and finger
kinematic data were extracted from ten able-bodied subjects while they were
tasked to do individual and simultaneous multiple finger flexion and extension
movements in free space. Instead of using traditional time-domain features of
EMG, an EMG-to-Muscle Activation model that parameterizes EMD was used and shown
to give better estimation performance. A fast feed forward artificial neural
network (ANN) and a nonparametric Gaussian Process (GP) regressor were both used
and evaluated to estimate complex finger kinematics, with the latter rarely used
in the other related literature. RESULTS: The estimation accuracies, in terms of
mean correlation coefficient, were 0.85 +/- 0.07, 0.78 +/- 0.06 and 0.73 +/- 0.04
for the metacarpophalangeal (MCP), proximal interphalangeal (PIP) and the distal
interphalangeal (DIP) finger joint DOFs, respectively. The mean root-mean-square
error in each individual DOF ranged from 5 to 15%. We show that estimation
improved using the proposed muscle activation inputs compared to other features,
and that using GP regression gave better estimation results when using fewer
training samples. CONCLUSION: The proposed method provides a viable means of
capturing the general trend of finger movements and shows a good way of
estimating finger joint kinematics using a muscle activation model that
parameterizes EMD. The results from this study demonstrates a potential control
strategy based on EMG that can be applied for simultaneous and continuous control
of multiple DOF(s) devices such as robotic hand/finger prostheses or
exoskeletons.
PMID- 25123026
TI - Could monitoring methylation markers aid the management of schizophrenia?
PMID- 25123025
TI - Biomarker and more: can translocator protein 18 kDa predict recovery from brain
injury and myocarditis?
PMID- 25123029
TI - Biomarkers and aging.
AB - Biomarkers and Ageing 25 February 2014, London, UK This conference was organized
by Euroscicon and was part of the 2014 Ageing Summit. The central theme was
biomarkers and aging including current research on biomarkers at the genomics and
proteomics level. The informal atmosphere of the conference promoted interaction
and networking opportunities between key leaders from industry, academic and
clinics. Presentations as well as the discussion panel session brought
opportunities to widely discuss the relevance of biomarkers as signatures for
human aging or age-related diseases. The meeting highlighted the importance of
genomics and regulatory elements in aging, their probable role in successful
aging and their potential interest for future antiaging approaches. The meeting
was chaired by David Melzer and Lorna Harries (University of Exeter, UK).
PMID- 25123030
TI - Development of NuQ nucleosome blood tests for the detection of colon cancer.
AB - Dr Jake Micallef speaks to Hannah L Wilson, Commissioning Editor: Dr Micallef has
20 years of experience in research and development and in the management of early
stage biotechnical companies, including the manufacture of biotechnology products
and the establishment of manufacturing operations. Dr Micallef gained this
experience while working for WHO over a 10-year period from 1985. While working
for WHO, Dr Micallef developed new diagnostic products in the areas of
reproductive health and cancer. In 1990 he commenced development of a new
diagnostic technology platform for WHO that was launched in 1992 and supported 13
tests. Dr Micallef also initiated and implemented in-house manufacture
(previously outsourced to Abbott Diagnostics Inc., Dartford, UK) and worldwide
distribution of these products for WHO. In 1990, he started a 'not-for-profit'
WHO company, Immunometrics Ltd (London, UK), which marketed and distributed those
diagnostic products worldwide. In 1999 Dr Micallef studied for an MBA and went on
to co-found Gene Expression Technologies Ltd (London, UK) in 2001 where he
successfully lead the development of the chemistry of the GeneICE technology and
implemented the manufacture of GeneICE molecules. He also played a major role in
business development and procured a GeneICE contract with Bayer Pharmaceuticals
(Leverkusen, Germany). From 2004 to 2007, he taught 'science and enterprise' to
science research workers from four universities at CASS Business School (London,
UK) before joining Cronos Therapeutics (London, UK) in 2004. In 2006 Cronos was
listed in the UK on AIM, becoming ValiRx. Dr Micallef continued to work as
Technical Officer for ValiRx, where he in-licensed the Hypergenomics and
Nucleosomics technologies and co-founded ValiBio SA (Namur, Belgium), which is
now Belgian Volition SA, a subsidiary of Singapore Volition. Dr Micallef was
educated at King's College London (UK; BSc, Biology and Chemistry, 1977; PhD
Physical Chemistry, 1981), St Thomas' Hospital Medical School, London (UK; MSc
Chemical Pathology, 1985) and Imperial College Management School (UK; MBA, 2000).
PMID- 25123031
TI - Dynamic sequencing of circulating tumor DNA: novel noninvasive cancer biomarker.
PMID- 25123032
TI - Pilot study of A-FABP levels as a predictive factor of SPECT results in
asymptomatic relatives of patients with cardiovascular disease.
AB - BACKGROUND: A-FABP is a promising link between metabolic syndrome and
atherosclerosis. It is not well known whether level of A-FABP predicts results of
SPECT. PATIENTS & METHODS: In 82 subjects (53 males) with a median age of 54
years, who were first-degree relatives of patients with cardiovascular disease,
the following tests and examinations were performed: A-FABP, calcium score (CS)
and SPECT. RESULTS: Subjects with positive and negative SPECT results differed
significantly in the noncategorized CS (p = 0.001), uric acid (p = 0.025) and the
total cholesterol:high-density lipoprotein ratio (p = 0.043), but not in other
parameters (including A-FABP). To predict SPECT results, the best model proved to
be a logistic regression model with gender and noncategorized CS as predictors,
with an area under the receiver operating characteristic curve of 0.89 (the
sensitivity and specificity based on a CS cutoff of 11.1 were 77.78 and 75.34%,
respectively). CONCLUSION: The serum level of A-FABP is not a predictor of a
positive SPECT result.
PMID- 25123034
TI - Circulating microparticles reflect treatment effects and clinical status in
multiple sclerosis.
AB - AIM: To evaluate whether circulating microparticles (MPs) derived from three cell
subtypes (platelets, total leukocytes or monocytes) obtained from multiple
sclerosis (MS) patients were modulated depending on the clinical status and to
investigate the effect of treatments on MP levels. PATIENTS & METHODS: The MP
counts were assessed with flow cytometry. RESULTS: The platelet-derived MP level
was higher in untreated MS patients than controls. Relapsing-remitting patients
showed the highest levels in the three subtypes of MP while secondary progressive
patients presented similar levels to those of healthy controls. Treatments had
significant effects increasing the three subtypes of MP counts. CONCLUSION: We
suggest that MPs play a role in MS pathogenesis, reflecting disease status with
an increment of their shedding during inflammatory periods and turning to
baseline during chronic progressive degeneration.
PMID- 25123033
TI - Sialylation of Thomsen-Friedenreich antigen is a noninvasive blood-based
biomarker for GNE myopathy.
AB - AIM: The exact pathomechanism of GNE myopathy remains elusive, but likely
involves aberrant sialylation. We explored sialylation status of blood-based
glycans as potential disease markers. METHODS: We employed immunoblotting, lectin
histochemistry and mass spectrometry. RESULTS: GNE myopathy muscle showed
hyposialylation of predominantly O-linked glycans. The O-linked glycome of
patients' plasma compared with controls showed increased amounts of desialylated
Thomsen-Friedenreich (T)-antigen, and/or decreased amounts of its sialylated
form, ST-antigen. Importantly, all patients had increased T/ST ratios compared
with controls. These ratios were normalized in a patient treated with intravenous
immunoglobulins as a source of sialic acid. DISCUSSION: GNE myopathy clinical
trial data will reveal whether T/ST ratios correlate to muscle function.
CONCLUSION: Plasma T/ST ratios are a robust blood-based biomarker for GNE
myopathy, and may also help explain the pathology and course of the disease.
PMID- 25123035
TI - Serum HER2 extracellular domain as a potential alternative for tissue HER2 status
in metastatic gastric cancer patients.
AB - AIM: We investigated whether serum concentrations of the HER2 extracellular
domain (ECD) can be used as an alternative to test tissue HER2 status in
metastatic gastric cancer. MATERIALS & METHODS: A total of 133 cases of
metastatic gastric cancer were included in present study. Serum HER2 ECD was
measured by chemiluminescence immunoassay (CLIA). Receiver operating
characteristic curve analysis was used to determine optimal serum HER2 ECD
concentrations for differentiation between positive and negative HER2 status.
RESULTS: The median level of serum HER2 ECD was 9.6 ng/ml in metastatic gastric
cancer patients. There was a significant relationship between serum and tissue
levels of HER2 protein (p < 0.001). Area under the curve for serum HER2 ECD was
0.771 (95% CI: 0.682-0.860). CONCLUSION: Levels of serum HER2 ECD are highly
correlated with tissue HER2 status in metastatic gastric cancer. Serum HER2 ECD
assay can be considered as a potential alternative for tissue HER2 status.
PMID- 25123036
TI - KLK11 mRNA expression predicts poor disease-free and overall survival in
colorectal adenocarcinoma patients.
AB - BACKGROUND: Dysregulated expression of several KLK family members has been
observed in colorectal adenocarcinoma. In the present study, the prognostic value
of KLK11 mRNA expression as a molecular tissue biomarker in colorectal
adenocarcinoma was examined. MATERIALS & METHODS: Using quantitative real-time
PCR, KLK11 mRNA expression was studied in 120 cancerous and 41 paired
noncancerous colorectal specimens obtained from 120 patients with primary
colorectal adenocarcinoma. RESULTS: A significant upregulation of KLK11
transcripts in colorectal tumors was observed. KLK11 mRNA expression was
associated with the depth of tumor invasion and the histological grade.
Furthermore, KLK11 mRNA expression predicted poor disease-free and overall
survival, independently of patient gender, age, tumor size, location,
histological subtype, grade, venous invasion, lymphatic invasion, TNM stage,
radiotherapy and chemotherapy treatment. CONCLUSION: KLK11 mRNA expression could
be considered as a new molecular prognostic biomarker in colorectal
adenocarcinoma, with additional prognostic value in patients with highly invasive
tumors and/or positive lymph nodes.
PMID- 25123037
TI - IGFBP1 in epithelial circulating tumor cells as a potential response marker to
selective internal radiation therapy in hepatocellular carcinoma.
AB - BACKGROUND: Local ablative techniques such as selective internal radiation
therapy (SIRT) have become the mainstay of treating hepatocellular carcinoma
(HCC) in the bridging-to-transplant and palliative setting. We recently
demonstrated that epithelial circulating tumor cells (CTCs) correlate to an
unfavorable outcome. We wanted to scrutinize whether molecular markers detected
in this specific CTC subgroup may also have clinical implications. MATERIALS &
METHODS: Mononuclear cells and CTCs were isolated from peripheral blood samples
using density gradient centrifugation followed by depletion of hematopoietic and
enrichment of epithelial (EpCAM(+)) cells employing immunomagnetic beads. The
mRNA expression of candidate markers was correlated with response to SIRT in 25
patients using quantitative real-time reverse-transcription PCR. RESULTS: IGFBP1
mRNA expression levels were significantly correlated with time to progression in
a Kaplan-Meier log rank test (p = 0.04; 0 vs 4 months) and receiver operating
characteristic analysis demonstrated a potential use to predict patients with
shortened time to progression (area under the curve: 0.8; 95% CI: 0.44-0.98; p =
0.03). CONCLUSION: The EpCAM fraction of CTCs may be useful to detect novel
molecular markers to individualize treatment decision in patients with HCC.
PMID- 25123038
TI - Novel single-chain antibody GD3A10 defines a chondroitin sulfate biomarker for
ovarian cancer.
AB - AIMS: Ovarian cancer has the highest case-to-fatality-index of all gynecological
cancers. In this study, tumor-related alterations in the extracellular matrix,
especially regarding chondroitin sulfate glycosaminoglycans, are proposed as a
novel biomarker in ovarian cancer. MATERIALS & METHODS: Phage display technology
was applied to select antibody GD3A10, which was obtained by biopanning using
embryonic glycosaminoglycans as a source for carcinogenic antigens. GD3A10
antigen specificity was studied in situ using glycosaminoglycan degrading
enzymes. A patient cohort (n = 159) was immunohistochemically stained. Scoring
was correlated with clinical prognostic parameters and survival. Normal rat
organs were used to study normal antigen distribution. RESULTS: GD3A10 is a
specific anti-chondroitin sulfate antibody and the epitope was absent or very
restricted in normal rat organs, normal ovaries and benign ovarian tumors. Strong
stromal expression was observed in malignant ovarian tumors, and correlated with
poor prognostic factors such as subtype, tumor grade and recurrence. CONCLUSION:
tumor-associated glycosaminoglycans are an interesting source of biomarkers in
ovarian cancer, as shown here using chondroitin sulfate antibody GD3A10.
PMID- 25123039
TI - Biomarkers of cartilage and surrounding joint tissue.
AB - The identification and clinical demonstration of efficacy and safety of osteo-
and chondro-protective drugs are met with certain difficulties. During the last
few decades, the pharmaceutical industry has, in the field of rheumatology,
experienced disappointments associated with the development of disease
modification. Today, the vast amount of patients suffering from serious, chronic
joint diseases can only be offered treatments aimed at improving symptoms, such
as pain and acute inflammation, and are not aimed at protecting the joint tissue.
This huge, unmet medical need has been the driver behind the development of
improved analytical techniques allowing better and more efficient clinical trial
design, implementation and analysis. With this review, we aim to provide a brief
and general overview of biochemical markers of joint tissue, with special focus
on neoepitopes. Furthermore, we highlight recent studies applying biochemical
markers in joint degenerative diseases. These disorders, including
osteoarthritis, rheumatoid arthritis and spondyloarthropathies, are the most
predominant disorders in Europe and the USA, and have enormous socioeconomical
impact.
PMID- 25123040
TI - miRNA panels as biomarkers for bladder cancer.
AB - AIM: Specific miRNA profiles have been identified for several samples from
patients with bladder cancer. The results are not always congruent and partly
contradictory. A comparison of published data was performed to select potential
markers. MATERIALS & METHODS: A literature search in PubMed identified 79
articles published prior to June 2013. Reports regarding the detection of miRNAs
in urine and blood have rarely been published; to date, nine respectively three
articles are available. RESULTS: The comparison of published data proved the
utility of miRNAs as diagnostic and prognostic indicators of bladder cancer. In
urine samples from bladder cancer patients, seven miRNAs were concordantly
expressed with tumor tissues. CONCLUSION: Standardization is strictly required in
pre-analytics and methods of miRNA measurements.
PMID- 25123041
TI - Implementation of PSA-based active surveillance in prostate cancer.
AB - Prostate cancer screening had led to the diagnosis of a large proportion of
localized and low-risk disease. Many of these cancer cases are believed to be
indolent and would not be clinically perceived in the absence of screening. In
addition to that, the wide use of active treatment has exposed these patients to
treatment-related quality-of-life impact. In this setting active surveillance as
a way of deferring active treatment and reserving such treatment to cases of
disease progression only has gained interest. PSA has been widely used to
identify patients eligible for active surveillance and also for disease
monitoring. The goal of this review was to describe the place of PSA in the
monitoring of patients under active surveillance based on the existing studies
and to discuss the importance of PSA in light of other existing or emerging tools
to monitor prostate cancer in active surveillance.
PMID- 25123042
TI - Detection of colorectal cancer by DNA methylation biomarker SEPT9: past, present
and future.
AB - Colorectal cancer has become the third most common cancer in the world. Early
diagnosis and treatment can significantly reduce colorectal cancer mortality. The
current routinely used fecal-based screening methods do not provide satisfactory
sensitivity. Although colonoscopy provides macroscopic diagnosis, the compliance
is low due to its inconvenience and complications. Hence, the development of new
screening methods is needed urgently. Peripheral blood SEPT9 gene methylation
assay has become a potential option with promising future for early detection and
screening of colorectal cancer. It is shown to be convenient, reliable with good
compliance by several clinical trials. This article will review the theoretical
foundation and development of the assay, focusing on its clinical trials,
comparing it with other screening methods and discussing its future applications.
PMID- 25123045
TI - Scratch wound closure of myoblasts and myotubes is reduced by inflammatory
mediators.
AB - Complex interactions exist between muscle repair processes and acute inflammatory
responses that are initiated by exercise-induced muscle damage. The purpose of
this study was to examine whether inflammatory mediators secreted by activated
macrophages affect the migration of myogenic cells to the injury site. Migration
was measured using a scratch wound closure assay in C2 C12 -derived myogenic
cells incubated in activated macrophage-conditioned medium. Both myoblast and
myotube migrations were significantly reduced in activated macrophage-conditioned
medium compared with control medium. Furthermore, we demonstrated that the
inhibitory effect on myoblast and myotube migrations was mediated, at least in
part, by the two major cytokines secreted by activated macrophages, tumour
necrosis factor (TNF)-alpha and interleukin (IL)-6. These findings suggest that
the migration rate of myogenic cells may be reduced by inflammatory mediators. It
may provide useful insights for future researches on the role of macrophages in
the process of muscle repair and regeneration.
PMID- 25123046
TI - Multicomponent reactions involving phosphines, arynes and aldehydes.
AB - Although nucleophilic phosphine-catalysis is a powerful tool for the construction
of various carbocycles and heterocycles, the reactions in which phosphines are
incorporated into the final product are rare, and the reports on phosphine
addition to highly electrophilic arynes are scarce. Herein, we report the
phosphine triggered multicomponent reaction of arynes and aldehydes, which takes
place via the formal [3+2] cycloaddition of an initially generated 1,3
phosphonium zwitterion from phosphines and arynes with aldehydes. The reaction
resulted in the formation of a diverse range of stable pentacovalent phosphoranes
in good yields based on the benzooxaphosphole system.
PMID- 25123044
TI - Effect of Part D coverage restrictions for antidepressants, antipsychotics, and
cholinesterase inhibitors on related nursing home resident outcomes.
AB - OBJECTIVES: In 2006, Medicare Part D transitioned prescription drug coverage for
dual-eligible nursing home residents from Medicaid to Medicare and randomly
assigned them to Part D prescription drug plans (PDPs). Because PDPs may differ
in coverage, plans may be more or less generous for drugs that an individual is
taking. Taking advantage of the fact that randomization mitigates potential
selection bias common in observational studies, this study sought to assess the
effect of PDP coverage on resident outcomes for three medication classes-
antidepressants, antipsychotics, and cholinesterase inhibitors. DESIGN:
Retrospective cohort study to examine the effect of coverage restrictions-
including noncoverage and coverage with restrictions--on depression,
hallucinations and delusions, aggressive behaviors, cognitive performance, and
activities of daily living for dual-eligible nursing home residents randomized to
PDPs in 2006 to 2008. The analyses further adjusted for baseline health status to
address any residual imbalances in the comparison groups. SETTING: Linked data
from Medicare claims, Minimum Data Set assessments, pharmacy claims, and PDP
formulary information. PARTICIPANTS: Dual-eligible nursing home residents aged 65
and older living in facilities that contracted with a single pharmacy provider.
RESULTS: PDP coverage restrictions in three medication classes of interest were
not significantly associated with the resident outcomes examined. Although
cholinesterase inhibitor users facing coverage restrictions had a 0.04-point
lower depression rating score than residents facing no restrictions, this
difference was not statistically significant after adjusting for multiple
comparisons. CONCLUSION: The findings suggest that exogenous changes in coverage
for three commonly used medication classes had no detectable effect on nursing
home resident outcomes in 2006 to 2008. There are several possible explanations
for this lack of association, including the role of policy protections for dual
eligible nursing home residents and the possibility that suitable clinical
alternatives were identified or that previously used medications offered little
clinical benefit.
PMID- 25123047
TI - Poor adherence to the World Health Organization guidelines of treatment of severe
pneumonia in children at Khartoum, Sudan.
AB - BACKGROUND: Community-acquired pneumonia (CAP) is as a major cause for childhood
morbidity and mortality worldwide. This study was conducted to investigate the
adherence and response of the WHO guidelines for treatment of severe pneumonia.
METHOD: A cross-sectional study was conducted in the period of June 2009 to July
2010 at Khartoum Hospital, Sudan. Children admitted and treated for severe
pneumonia were enrolled. RESULTS: Only 39 (18.8%) out of 208 enrolled children
received prescriptions that were adherent to the WHO guidelines of treatment of
severe pneumonia. In logistic regression none of the investigated variable (age,
gender, and clinical presentations) was associated with the adherence to the WHO
guidelines. There was no significant difference in the response between adherent
and non-adherent prescriptions. There was no association between the demographic,
clinical data, treatment-adherence to the guidelines and the patients' response.
CONCLUSION: There is a poor (18.8%) adherence to the WHO guidelines of the
treatment of severe pneumonia in the region regardless to the age, gender and
clinical presentation.
PMID- 25123048
TI - Quality assessment of 3D-CTVR, MPR and section plane techniques in ossicular
chain reconstruction in middle ear cholesteatoma.
AB - AIM: To assess the quality of three-dimensional volume rendered computer
tomography (3D-CTVR), multi-planar reformation (MPR) and CT section plane in the
fine diagnosis of ossicular chain in middle ear cholesteatoma. METHODS: Sixty
patients with middle ear cholesteatoma were selected in this retrospective study.
All cases underwent pre-operative CT scan. The respective radiologic reports of
the ossicles status via three protocols were then compared to surgical findings.
RESULTS: Quality assessment of these three protocols in the fine diagnosis of
fine ossicles buried inside the soft tissue showed that both CTVR and MPR are
more superior to conventional section plane, especially CTVR. CONCLUSION: The
uses of CTVR and MPR, in conjunction with conventional section plane, are better
able to show where the true and fine ossicular chain in the cholesteatoma mass
is. In the final analysis, we believe that the use of CTVR and MPR techniques can
have profound contributive value in future clinical work.
PMID- 25123050
TI - Bovine tuberculosis slaughter surveillance in the United States 2001-2010:
assessment of its traceback investigation function.
AB - BACKGROUND: The success of tracing cattle to the herd of origin after the
detection and confirmation of bovine tuberculosis (TB) lesions in cattle at
slaughter is a critical component of the national bovine TB eradication program
in the United States (U.S.). The aims of this study were to 1) quantify the
number of bovine TB cases identified at slaughter that were successfully traced
to their herd of origin in the U.S. during 2001-2010, 2) quantify the number of
successful traceback investigations that found additional TB infected animals in
the herd of origin or epidemiologically linked herds, and 3) describe the forms
of animal identification present on domestic bovine TB cases and their
association with traceback success. RESULTS: We analyzed 2001-2010 data in which
371 granulomatous lesions were confirmed as bovine TB. From these 114 bovine TB
cases, 78 adults (i.e. sexually intact bovines greater than two years of age),
and 36 fed (i.e. less than or equal to two years of age) were classified as
domestic cattle (U.S. originated). Of these adults and fed cases, 83% and 13%
were successfully traced, respectively. Of these traceback investigations, 70% of
adult cases and 50% of fed cases identified additional bovine TB infected animals
in the herd of origin or an epidemiologically linked herd. We found that the
presence of various forms of animal identification on domestic bovine TB cases at
slaughter may facilitate successful traceback investigations; however, they do
not guarantee it. CONCLUSIONS: These results provide valuable information with
regard to epidemiological traceback investigations and serve as a baseline to aid
U.S. officials when assessing the impact of newly implemented strategies as part
of the national bovine TB eradication in the U.S.
PMID- 25123051
TI - Comparison of three noninvasive methods for hemoglobin screening of blood donors.
AB - BACKGROUND: To prevent phlebotomy of anemic individuals and to ensure hemoglobin
(Hb) content of the blood units, Hb screening of blood donors before donation is
essential. Hb values are mostly evaluated by measurement of capillary blood
obtained from fingerstick. Rapid noninvasive methods have recently become
available and may be preferred by donors and staff. The aim of this study was to
evaluate for the first time all different noninvasive methods for Hb screening.
STUDY DESIGN AND METHODS: Blood donors were screened for Hb levels in three
different trials using three different noninvasive methods (Haemospect [MBR
Optical Systems GmbH & Co. KG], NBM 200 [LMB Technology GmbH], Pronto-7 [Masimo
Europe Ltd]) in comparison to the established fingerstick method (CompoLab Hb
[Fresenius Kabi GmbH]) and to levels obtained from venous samples on a cell
counter (Sysmex [Sysmex Europe GmbH]) as reference. The usability of the
noninvasive methods was assessed with an especially developed survey. RESULTS:
Technical failures occurred by using the Pronto-7 due to nail polish, skin color,
or ambient light. The NBM 200 also showed a high sensitivity to ambient light and
noticeably lower Hb levels for women than obtained from the Sysmex. The
statistical analysis showed the following bias and standard deviation of
differences of all methods in comparison to the venous results: Haemospect, -0.22
+/- 1.24; NBM, 200 -0.12 +/- 1.14; Pronto-7, -0.50 +/- 0.99; and CompoLab Hb,
0.53 +/- 0.81. CONCLUSION: Noninvasive Hb tests represent an attractive
alternative by eliminating pain and reducing risks of blood contamination. The
main problem for generating reliable results seems to be preanalytical
variability in sampling. Despite the sensitivity to environmental stress, all
methods are suitable for Hb measurement.
PMID- 25123052
TI - Low physiological levels of prostaglandins E2 and F2alpha improve human sperm
functions.
AB - Prostaglandins (PGs) have been reported to be present in the seminal fluid and
cervical mucus, affecting different stages of sperm maturation from
spermatogenesis to the acrosome reaction. This study assessed the effects of low
physiological PGE2 and PGF2alpha concentrations on human sperm motility and on
the ability of the spermatozoa to bind to the zona pellucida (ZP). Human
spermatozoa were isolated from seminal samples with normal concentration and
motility parameters and incubated with 1MUM PGE2, 1MUM PGF2alpha or control
solution to determine sperm motility and the ability to bind to human ZP. The
effects of both PGs on intracellular calcium levels were determined. Incubation
for 2 or 18h with PGE2 or PGF2alpha resulted in a significant (P<0.05) increase
in the percentage of spermatozoa with progressive motility. In contrast with
PGF2alpha, PGE2 alone induced an increase in sperm intracellular calcium levels;
however, the percentage of sperm bound to the human ZP was doubled for both PGs.
These results indicate that incubation of human spermatozoa with low
physiological levels of PGE2 or PGF2alpha increases sperm functions and could
improve conditions for assisted reproduction protocols.
PMID- 25123053
TI - Pre-existing anti-HLA antibodies negatively impact survival of pediatric aplastic
anemia patients undergoing HSCT.
AB - Graft failure and survival are the major problems for patients with aplastic
anemia undergoing hematopoietic stem cell transplantation (HSCT). Previous
studies showed that anti-HLA antibodies negatively impact engraftment in HSCT.
This retrospective study of 51 pediatric patients with acquired aplastic anemia
who underwent allogeneic HSCT at a single institution between 2006 and 2012
investigated the influence of anti-HLA antibodies on the outcome of HSCT. Serum
samples collected before HSCT were tested for the presence of anti-HLA
antibodies. Pre-existing anti-HLA antibodies were detected in 54.9% (28/51) of
patients, among whom 39.2% (20/51) had anti-HLA class I antibodies. Anti-HLA
antibodies were associated with worse five-yr survival (78.6% vs. 100%, p =
0.021) and higher treatment-related mortality (21.4% vs. 0%, p = 0.028) compared
with antibody-negative patients. Anti-HLA class I antibody-positive patients had
poorer five-yr survival (75.0%) than anti-HLA class I&II antibody-positive and
antibody-negative patients (87.5% and 100.0%, respectively, p = 0.039). Presence
of anti-HLA class I antibodies (p = 0.024) and older age (10 yr or more; p =
0.027) significantly increased the risk of post-HSCT mortality. Pre-existing anti
HLA antibodies negatively affect the outcome of HSCT in pediatric patients with
aplastic anemia. Routine testing for anti-HLA antibodies concurrent with
efficient treatment should be conducted prior to HSCT.
PMID- 25123054
TI - Tobacco use and smoking cessation among third-year dental students in southern
Brazil.
AB - The aim of the present cross-sectional study was to assess tobacco use and
smoking cessation among third-year dental students in southern Brazil. The Global
Health Professions Student Survey questionnaire was used in eight dental schools
in Rio Grande do Sul state, Brazil. Of the 663 eligible students, 576 (87%)
participated. The prevalence of current smoking was 19.1% [95% confidence
interval (CI): 12.9-25.3%], and 61.6% (95% CI: 54.9-68.3%) of students reported
having smoked at least once in their lifetime. The prevalence of dental students
who had smoked >= 100 cigarettes in their lifetime was 17.1% (95% CI: 12.5
21.7%). Being frequently exposed to other smokers at home or in other places
(second-hand smoke) increased the likelihood of current smoking by two- to
threefold. Approximately 6.1% (95% CI: 3.5-8.7%) of the students reported that
they currently wanted to stop smoking and 7.5% (95% CI: 5.3-9.6%) had tried to
stop smoking in the last year. Friends and family were the most frequent sources
of help or counselling, and only a limited proportion of students received help
from health professionals. Tobacco use and exposure to second-hand smoking is
widespread among dental students in southern Brazil. Smoking-cessation
initiatives targeting health care students are urgently needed.
PMID- 25123049
TI - Daily torpor and hibernation in birds and mammals.
AB - Many birds and mammals drastically reduce their energy expenditure during times
of cold exposure, food shortage, or drought, by temporarily abandoning euthermia,
i.e. the maintenance of high body temperatures. Traditionally, two different
types of heterothermy, i.e. hypometabolic states associated with low body
temperature (torpor), have been distinguished: daily torpor, which lasts less
than 24 h and is accompanied by continued foraging, versus hibernation, with
torpor bouts lasting consecutive days to several weeks in animals that usually do
not forage but rely on energy stores, either food caches or body energy reserves.
This classification of torpor types has been challenged, suggesting that these
phenotypes may merely represent extremes in a continuum of traits. Here, we
investigate whether variables of torpor in 214 species (43 birds and 171 mammals)
form a continuum or a bimodal distribution. We use Gaussian-mixture cluster
analysis as well as phylogenetically informed regressions to quantitatively
assess the distinction between hibernation and daily torpor and to evaluate the
impact of body mass and geographical distribution of species on torpor traits.
Cluster analysis clearly confirmed the classical distinction between daily torpor
and hibernation. Overall, heterothermic endotherms tend to be small; hibernators
are significantly heavier than daily heterotherms and also are distributed at
higher average latitudes (~35 degrees ) than daily heterotherms (~25 degrees ).
Variables of torpor for an average 30 g heterotherm differed significantly
between daily heterotherms and hibernators. Average maximum torpor bout duration
was >30-fold longer, and mean torpor bout duration >25-fold longer in
hibernators. Mean minimum body temperature differed by ~13 degrees C, and the
mean minimum torpor metabolic rate was ~35% of the basal metabolic rate (BMR) in
daily heterotherms but only 6% of BMR in hibernators. Consequently, our analysis
strongly supports the view that hibernators and daily heterotherms are
functionally distinct groups that probably have been subject to disruptive
selection. Arguably, the primary physiological difference between daily torpor
and hibernation, which leads to a variety of derived further distinct
characteristics, is the temporal control of entry into and arousal from torpor,
which is governed by the circadian clock in daily heterotherms, but apparently
not in hibernators.
PMID- 25123055
TI - Comparison of three methods for detection of gametocytes in Melanesian children
treated for uncomplicated malaria.
AB - BACKGROUND: Gametocytes are the transmission stages of Plasmodium parasites, the
causative agents of malaria. As their density in the human host is typically low,
they are often undetected by conventional light microscopy. Furthermore,
application of RNA-based molecular detection methods for gametocyte detection
remains challenging in remote field settings. In the present study, a detailed
comparison of three methods, namely light microscopy, magnetic fractionation and
reverse transcriptase polymerase chain reaction for detection of Plasmodium
falciparum and Plasmodium vivax gametocytes was conducted. METHODS: Peripheral
blood samples from 70 children aged 0.5 to five years with uncomplicated malaria
who were treated with either artemether-lumefantrine or artemisinin-naphthoquine
were collected from two health facilities on the north coast of Papua New Guinea.
The samples were taken prior to treatment (day 0) and at pre-specified intervals
during follow-up. Gametocytes were measured in each sample by three methods: i)
light microscopy (LM), ii) quantitative magnetic fractionation (MF) and, iii)
reverse transcriptase PCR (RTPCR). Data were analysed using censored linear
regression and Bland and Altman techniques. RESULTS: MF and RTPCR were similarly
sensitive and specific, and both were superior to LM. Overall, there were
approximately 20% gametocyte-positive samples by LM, whereas gametocyte
positivity by MF and RTPCR were both more than two-fold this level. In the subset
of samples collected prior to treatment, 29% of children were positive by LM, and
85% were gametocyte positive by MF and RTPCR, respectively. CONCLUSIONS: The
present study represents the first direct comparison of standard LM, MF and RTPCR
for gametocyte detection in field isolates. It provides strong evidence that MF
is superior to LM and can be used to detect gametocytaemic patients under field
conditions with similar sensitivity and specificity as RTPCR.
PMID- 25123056
TI - Pulmonary microvascular lesions regress in reperfused chronic thromboembolic
pulmonary hypertension.
AB - BACKGROUND: Pulmonary microvascular disease (PMD) develops in both occluded and
non-occluded territories in patients with chronic thromboembolic pulmonary
hypertension (CTEPH) and may cause persistent pulmonary hypertension after
pulmonary endarterectomy. Endothelin-1 (ET-1) and interleukin-6 (IL-6) are
potential PMD severity biomarkers, but it remains unknown whether they are
related to occluded or non-occluded territories. We assessed PMD and ET-1/IL-6
gene expression profiles in occluded and non-occluded territories with and
without chronic lung reperfusion in an animal CTEPH model. METHODS: Chronic PH
was induced in 10 piglets by left pulmonary artery (PA) ligation followed by
weekly embolization of right lower lobe arteries with enbucrilate tissue adhesive
for 5 weeks. At Week 6, 5 of 10 animals underwent left PA reperfusion. At Week
12, animals with and without reperfusion were compared with sham animals (n = 5).
Hemodynamics, lung morphometry and ET-1/IL-6 gene expression profiles were
assessed in the left lung (LL, occluded territories) and right upper lobe (RUL,
non-occluded territories). RESULTS: At Week 12, mean PA pressure remained
elevated without reperfusion (29.0 +/- 2.8 vs 27.0 +/- 1.1 mm Hg, p = 0.502), but
decreased after reperfusion (30.0 +/- 1.5 vs 20.5 +/- 1.7 mm Hg, p = 0.013).
Distal media thickness in the LL and RUL PAs and systemic vasculature to the LL
were significantly lower in the reperfused and sham groups compared with the non
reperfused group. PMD progression was related to ET-1 and IL-6 gene expression in
the RUL and to the ET-A/ET-B gene expression ratio in the LL. CONCLUSIONS: PMD
regressed in occluded and non-occluded territories after lung reperfusion.
Changes in ET-1 and IL-6 gene expression were associated with PMD in non-occluded
territories.
PMID- 25123057
TI - Four types of Bifidobacteria trigger autophagy response in intestinal epithelial
cells.
AB - OBJECTIVES: To investigate the influence of gut microbiota on autophagy
activation in intestinal epithelial cells (IEC) and to evaluate the IEC autophagy
response to different types of Bifidobacteria. METHODS: IEC-18 cells were treated
with lipopolysaccharide (LPS) derived from enteropathogenic Escherichia coli
(EPEC) O127:B8 and culture medium supernatants of four types of Bifidobacteria.
Transepithelial electrical resistance (TEER) was measured using an epithelial
voltohmmeter. Autophagy was determined by transmission electron microscopy (TEM),
the ratio of LC3-II to LC3-I and the persistence of both green fluorescent
protein (GFP) and mCherry signals using a tandem mCherry-GFP-LC3 construct. The
expression of Atg12-Atg5-Atg16 complex was measured by quantitative real-time
polymerase chain reaction. RESULTS: EPEC-LPS significantly diminished the TEER of
IEC compared with untreated controls by 45-55%. This reduction was not observed
after treated with Bifidobacteria at all time points. Bifidobacteria could
initiate the activation of autophagy in IEC, based on both the ratio of LC3-II to
LC3-I and TEM. There was no difference in the influence of the four types of
Bifidobacteria on the autophagy response. Compared with Bifidobacteria, IEC
reacted to EPEC-LPS much more intensively by autophagy accumulation. More
mCherry(+) LC3 autophagic puncta and increased expressions of autophagy genes
Atg5, Atg12 and Atg16 could be detected after being treated with Bifidobacteria
and EPEC-LPS. CONCLUSIONS: Bifidobacteria initiate autophagy activation in IEC.
The Atg12-Atg5-Atg16 multimeric complex might participate in the activation of
Bifidobacteria-induced cell autophagy.
PMID- 25123058
TI - Electroneutralized amphiphilic triblock copolymer with a peptide dendron for
efficient muscular gene delivery.
AB - Hydrophilic-hydrophobic-hydrophilic triblock copolymers, such as Pluronic L64,
P85, and P105, have attracted more attention due to their enhancement in muscular
gene delivery. In the present study, a new kind of electroneutralized triblock
copolymer, LPL, dendron G2(L-lysine-Boc)-PEG2k-dendron G2(L-lysine-Boc), was
designed and investigated. This hydrophobic-hydrophilic-hydrophobic copolymer is
composed of a structure reverse to that of L64, one of the most effective
materials for intramuscular gene delivery so far. Our results showed that LPL
exhibited good in vivo biocompatibility after intramuscular and intravenous
administration. LPL mediated higher reporter gene expression than L64 in assays
of beta-galactosidase (LacZ), luciferase, and fluorescent protein E2-Crimson.
Furthermore, LPL-mediated mouse growth hormone expression significantly
accelerated mouse growth within the first 10 days. Altogether, LPL-mediated gene
expression in skeletal muscle exhibits the potential of successful gene therapy.
The current study also presented an innovative way to design and construct new
electroneutralized triblock copolymers for safe and effective intramuscular gene
delivery.
PMID- 25123059
TI - Relationship between patient-perceived vocal handicap and clinician-rated level
of vocal dysfunction.
AB - OBJECTIVES/HYPOTHESIS: The relationship between patient-reported vocal handicap
and clinician-rated measures of vocal dysfunction is not understood. This study
aimed to determine if a correlation exists between the Voice Handicap Index-10
(VHI-10) and the Voice Functional Communication Measure rating in the National
Outcomes Measurement System (NOMS). STUDY DESIGN: Retrospective case series.
METHODS: Four hundred and nine voice evaluations over 12 months at a tertiary
voice center were reviewed. The VHI-10 and NOMS scores, diagnoses, and potential
comorbid factors were collected and analyzed. RESULTS: For the study population
as a whole, there was a moderate negative correlation between the NOMS rating and
the VHI-10 (Pearson r = -0.57). However, for a given NOMS level, there could be
considerable spread in the VHI-10. In addition, as the NOMS decreased stepwise
below level 4, there was a corresponding increase in the VHI-10. However, a
similar trend in VHI-10 was not observed for NOMS above level 4, indicating the
NOMS versus VHI-10 correlation was not linear. Among diagnostic groups, the
strongest correlation was found for subjects with functional dysphonia. The NOMS
versus VHI-10 correlation was not affected by gender or the coexistence of a
psychiatric diagnosis. CONCLUSIONS: A simple relationship between VHI-10 and NOMS
rating does not exist. Patients with mild vocal dysfunction have a less direct
relationship between their NOMS ratings and the VHI-10. These findings provide
insight into the interpretation of patient-perceived and clinician-rated measures
of vocal function and may allow for better management of expectations and patient
counseling in the treatment of voice disorders.
PMID- 25123060
TI - A new, microalgal DHA- and EPA-containing oil lowers triacylglycerols in adults
with mild-to-moderate hypertriglyceridemia.
AB - In this double-blind, parallel trial, 93 healthy adults with hypertriglyceridemia
(triacylglycerols [TAG] 150-499 mg/dL) were randomized to receive either a
nutritional oil derived from marine algae (DHA-O; 2.4 g/day docosahexaenoic acid
[DHA] and eicosapentaenoic acid [EPA] in a 2.7:1 ratio), fish oil (FO; 2.0 g/day
DHA and EPA in a 0.7:1 ratio), or a corn oil/soy oil control as 4-1g softgel
capsules/day with meals for 14 weeks; and were instructed to maintain their
habitual diet. Percent changes from baseline for DHA-O, FO, and control,
respectively, were TAG (-18.9, -22.9, 3.5; p<0.001 DHA-O and FO vs. control), low
density lipoprotein cholesterol (4.6, 6.8, -0.6; p<0.05 DHA-O and FO vs.
control), and high-density lipoprotein cholesterol (4.3, 6.9, 0.6; p<0.05 FO vs.
control). This study demonstrated that ingestion of microalgal DHA-O providing
2.4 g/day DHA+EPA lowered TAG levels to a degree that was not different from that
of a standard fish oil product, and that was significantly more than for a corn
oil/soy oil control.
PMID- 25123061
TI - Heterogeneity in cord blood DHA concentration: towards an explanation.
AB - This paper aimed to identify the dietary and non-dietary determinants of
docosahexaenoic acid (DHA) levels in umbilical cord blood at delivery. DHA was
measured in cord blood plasma phospholipids of 1571 participants from the DOMInO
(DHA to Optimize Mother Infant Outcome) randomized controlled trial.
Socioeconomic, lifestyle and clinical data relating to the mother and current
pregnancy were obtained from all women and their relationships with cord blood
DHA assessed. DHA concentrations in the cord plasma phospholipids at delivery
covered a 3-4 fold range in both control and DHA groups. The total number of DHA
rich intervention supplement capsules consumed over the course of pregnancy and
gestational age at delivery individually explained 21% and 16% respectively of
the variation in DHA abundance in the cord blood plasma phospholipids at
delivery, but no other clinical or life-style factors explored in this study
could account for >2% of the variation. Indeed, more than 65% of the variation
remained unaccounted for even when all factors were included in the analysis.
These data suggest that factors other than maternal DHA intake have an important
role in determining cord blood DHA concentrations at delivery, and may at least
partially explain the variation in the response of infants to maternal DHA
supplementation reported in published trials.
PMID- 25123062
TI - Gene expression of fatty acid transport and binding proteins in the blood-brain
barrier and the cerebral cortex of the rat: differences across development and
with different DHA brain status.
AB - Specific mechanisms for maintaining docosahexaenoic acid (DHA) concentration in
brain cells but also transporting DHA from the blood across the blood-brain
barrier (BBB) are not agreed upon. Our main objective was therefore to evaluate
the level of gene expression of fatty acid transport and fatty acid binding
proteins in the cerebral cortex and at the BBB level during the perinatal period
of active brain DHA accretion, at weaning, and until the adult age. We measured
by real time RT-PCR the mRNA expression of different isoforms of fatty acid
transport proteins (FATPs), long-chain acyl-CoA synthetases (ACSLs), fatty acid
binding proteins (FABPs) and the fatty acid transporter (FAT)/CD36 in cerebral
cortex and isolated microvessels at embryonic day 18 (E18) and postnatal days 14,
21 and 60 (P14, P21 and P60, respectively) in rats receiving different n-3 PUFA
dietary supplies (control, totally deficient or DHA-supplemented). In control
rats, all the genes were expressed at the BBB level (P14 to P60), the mRNA levels
of FABP5 and ACSL3 having the highest values. Age-dependent differences included
a systematic decrease in the mRNA expressions between P14-P21 and P60 (2 to 3
fold), with FABP7 mRNA abundance being the most affected (10-fold). In the
cerebral cortex, mRNA levels varied differently since FATP4, ACSL3 and ACSL6 and
the three FABPs genes were highly expressed. There were no significant
differences in the expression of the 10 genes studied in n-3 deficient or DHA
supplemented rats despite significant differences in their brain DHA content,
suggesting that brain DHA uptake from the blood does not necessarily require
specific transporters within cerebral endothelial cells and could, under these
experimental conditions, be a simple passive diffusion process.
PMID- 25123064
TI - Fluorescence in-situ hybridization identifies Mastermind-like 2 (MAML2)
rearrangement in odontogenic cysts with mucous prosoplasia: a pilot study.
AB - AIMS: The pathogenesis of intraosseous mucoepidermoid carcinoma (IMEC) remains
unknown. Coexistence with odontogenic cysts (ODC) has been reported in 32-48% of
IMEC. Furthermore, prosoplastic mucous cells are often seen in the epithelial
lining of ODCs. MECT1-MAML2 fusion transcripts have been identified in >66% of
salivary gland MEC cases. The aim of this study was to investigate the presence
of MAML2 rearrangement in ODCs featuring mucous prosoplasia. METHODS AND RESULTS:
Ten cases of ODC with a mucous cell component and three cases of IMEC were
evaluated using fluorescence in-situ hybridization. All cases occurred in the
mandible. The ODCs exhibited a M:F ratio of 4:1 (mean age 49.2 years), while all
IMECs occurred in women (mean age 68.3 years). All three IMECs demonstrated MAML2
rearrangement, in 26-61% of tumour cells. Successful hybridization was observed
in nine of 10 cases of ODC. In two of these nine, there was MAML2 rearrangement
in 12% and 24% of the lining epithelial cells, while three of the nine showed
rearrangement in 7-8% of cells; the remaining four cases were negative.
CONCLUSIONS: We identified MAML2 rearrangements in five of nine ODCs lined by
mucus-secreting cells. This suggests that at least a subset of ODCs with mucous
prosoplasia are characterized by molecular events considered diagnostic for
intraosseous and extraosseous MEC.
PMID- 25123065
TI - [Comorbidity in 207 cannabis users in a specific outpatient setting].
AB - BACKGROUND: Health care seeking for a problematic use of cannabis is in progress
in France. OBJECTIVES: The aim is to assess the addictive and psychiatric
comorbidity in cannabis users seen in the specific setting at the Lariboisiere
hospital. METHOD: Two hundred and seven cannabis users were included from January
2004 to December 2009. Twelve-month and lifetime diagnosis of abuse and
dependence (cannabis, alcohol, cocaine/crack) (DSM-IV), current and lifetime mood
disorders, anxiety disorders, eating disorders and psychotic disorders were
assessed (Mini-International Neuropsychiatric Interview). Logistic regression
analyses identified adjusted odds ratios associated with the gender and the
health care seeking (P=0.01). RESULTS: One hundred and forty-seven men (71%) and
60 women (29%), 29.3+/-8.6 years (15.2-51.6 years). Most of the outpatients ask
for health care themselves (59.7%), whereas 19.4% are asked to seek health care
by relatives (19.4%) or because of an academic, health or justice injunction
(20.4%). In total, 49.3% of the outpatients are single, 35.7% are cohabitating,
9.3% are married and 6.3% are separated/divorced. About 20.4% of the outpatients
are students, 35.7% have a professional activity, 19% are jobless, 2.4% are
impaired, 0.5% are retired, at home and 12.1% do not have an official income.
Twelve-month and lifetime prevalence of abuse/dependence are: cannabis
(10.1/82.1% and 8.7/88.4%), alcohol (9.7/8.7% and 19.3/18.8%), cocaine/crack
(2.4/3.4% and 4.8/11.6%). The mean duration of cannabis dependence for the
current dependent users is 8.4+/-5.8 years. The mean number of "joints" during
the last 6 months is 6+/-4.3, the mean amount of cannabis per week is 12.5+/
11.3g. About 51.3% of the dependent users report externalized and/or internalized
disorders at school during childhood and adolescence. In total, 19.4% of the
dependent users have a suicide attempt history and 18.9% have a psychiatric
hospitalisation history, more frequently women (P<0.01 and P=0.02). About 73.8%
have a psychologist or psychiatrist care history. In total, 38.1% of users have
at least one current mood disorder, females more frequently than males (P<0.001).
Current and lifetime prevalence of mood disorders are: major depressive disorder
(MDD) (29.1% and 57.1%); current dysthymia (20.3%); hypomania (1.9 and 6.7%);
mania (2.9 and 12.8%). Females have more frequently than males current and
lifetime MDD (P<0.001). About 53.2% of users have at least one current anxiety
disorder, females more frequently than males (P<0.001). Current and lifetime
prevalence of anxiety disorders are: panic disorder (10 and 16.4%); agoraphobia
(13.9 and 17.4%); social phobia (26.9 and 32.8%); obsessive-compulsive disorder
(9.5 and 12.9%); post-traumatic stress disorder (PTSD) (6.5 and 16.4%); current
generalized anxiety disorder (26.8%). Females have more frequently current and
lifetime: agoraphobia (P=0.01 and P<0.001); PTSD (P<0.001); current social phobia
(P=0.049). Current and lifetime eating disorders prevalence are: anorexia (0 and
1.5%); bulimia (4 and 8%); females more frequently have bulimia (P=0.02 and
P<0.001). In total, 4.8% have a psychotic disorder. Adjusted odds ratios of
associated variables to gender (women/men) are lifetime MDD OR=4.71 [2.1-10.61]
(P<0.001) and later age of onset of cannabis abuse OR=1.1 [1.04-1.17] (P=0.002).
Adjusted odds ratios associated with personal health care seeking compared to a
non personal motivated health care seeking are the numbers of criteria of 12
month cannabis dependence OR=1.26 [1.06-1.51] (P=0.009) and age OR=1.07 [1.03
1.12] (P=0.002). CONCLUSION: Our survey confirms the high mood and anxiety
disorders comorbidity in cannabis dependent users seen in a specific setting and
underlines the need to evaluate those disorders.
PMID- 25123063
TI - MxB binds to the HIV-1 core and prevents the uncoating process of HIV-1.
AB - BACKGROUND: The IFN-alpha-inducible restriction factor MxB blocks HIV-1 infection
after reverse transcription but prior to integration. Genetic evidence suggested
that capsid is the viral determinant for restriction by MxB. This work explores
the ability of MxB to bind to the HIV-1 core, and the role of capsid-binding in
restriction. RESULTS: We showed that MxB binds to the HIV-1 core and that this
interaction leads to inhibition of the uncoating process of HIV-1. These results
identify MxB as an endogenously expressed protein with the ability to inhibit HIV
1 uncoating. In addition, we found that a benzimidazole-based compound known to
have a binding pocket on the surface of the HIV-1 capsid prevents the binding of
MxB to capsid. The use of this small-molecule identified the MxB binding region
on the surface of the HIV-1 core. Domain mapping experiments revealed the
following requirements for restriction: 1) MxB binding to the HIV-1 capsid, which
requires the 20 N-terminal amino acids, and 2) oligomerization of MxB, which is
mediated by the C-terminal domain provides the avidity for the interaction of MxB
with the HIV-1 core. CONCLUSIONS: Overall our work establishes that MxB binds to
the HIV-1 core and inhibits the uncoating process of HIV-1. Moreover, we
demonstrated that HIV-1 restriction by MxB requires capsid binding and
oligomerization.
PMID- 25123066
TI - A multiplanar complex resection of a low-grade chondrosarcoma of the distal femur
guided by K-wires previously inserted under CT-guide: a case report.
AB - BACKGROUND: In muscular skeletal oncology aiming to achieve wide surgical margin
is one of the main factors influencing patient prognosis. In cases where lesions
are either meta or epiphyseal, surgery most often compromises joint integrity and
stability because muscles, tendons and ligaments are involved in wide resection.
When lesions are well circumscribed they can be completely resected by performing
multi-planar osteotomies guided by computer-assisted navigation. We describe a
case of low-grade chondrosarcoma of the distal femur where a simple but effective
technique was useful to perform complex multiplanar osteotomies. No similar
techniques are reported in the literature. CASE PRESENTATION: A 57 year-old
Caucasian female was referred to our department for the presence of a distal
femur chondrosarcoma. A resection with the presenting technique was scheduled.
The first step consists of inserting several K-wires under CT-scan control to
delimitate the tumor; the second step consists of tumor removal: in operative
theatre, following surgical access, k-wires are used as guide positioning;
scalpels are externally placed to k-wires to perform a safe osteotomy.
CONCLUSIONS: Computed assisted resections can be considered the most advantageous
method to reach the best surgical outcome; unfortunately navigation systems are
only available in specialized centres. The present technique allows for a
multiplanar complex resection when navigation systems are not available. This
technique can be applied in low-grade tumours where a minimal wide margin can be
considered sufficient.
PMID- 25123067
TI - Echinococcus as a model system: biology and epidemiology.
AB - The introduction of Echinococcus to Australia over 200 years ago and its
establishment in sheep rearing areas of the country inflicted a serious medical
and economic burden on the country. This resulted in an investment in both basic
and applied research aimed at learning more about the biology and life cycle of
Echinococcus. This research served to illustrate the uniqueness of the parasite
in terms of developmental biology and ecology, and the value of Echinococcus as a
model system in a broad range of research, from fundamental biology to
theoretical control systems. These studies formed the foundation for an
international, diverse and ongoing research effort on the hydatid organisms
encompassing stem cell biology, gene regulation, strain variation, wildlife
diseases and models of transmission dynamics. We describe the development, nature
and diversity of this research, and how it was initiated in Australia but
subsequently has stimulated much international and collaborative research on
Echinococcus.
PMID- 25123068
TI - Genetic diversity of the Chinese liver fluke Clonorchis sinensis from Russia and
Vietnam.
AB - Clonorchiasis is a parasitic disease of high public health importance in many
countries in southeastern Asia and is caused by the Chinese liver fluke
Clonorchis sinensis. However, the genetic structure and demographic history of
its populations has not been sufficiently studied throughout the geographic range
of the species and available data are based mainly on partial gene sequencing. In
this study, we explored the genetic diversity of the complete 1560 bp cytochrome
c oxidase subunit 1 (cox1) gene sequence for geographically isolated C. sinensis
populations in Russia and Vietnam, to our knowledge for the first time. The
results demonstrated low nucleotide and high haplotype differentiation within and
between the two compared regions and a clear geographical vector for the
distribution of genetic diversity patterns among the studied populations. These
results suggest a deep local adaptation of the parasite to its environment
including intermediate hosts and the existence of gene flow across the species'
range. Additionally, we have predicted an amino acid substitution in the
functional site of the COX1 protein among the Vietnamese populations, which were
reported to be difficult to treat with praziquantel. The haplotype networks
consisted of several region-specific phylogenetic lineages, the formation of
which could have occurred during the most extensive penultimate glaciations in
the Pleistocene Epoch. The patterns of genetic diversity and demographics are
consistent with population growth of the liver fluke in the late Pleistocene
following the Last Glacial Maximum, indicating the lack of a population
bottleneck during the recent past in the species' history. The data obtained have
important implications for understanding the phylogeography of C. sinensis, its
host-parasite interactions, the ability of this parasite to evolve drug
resistance, and the epidemiology of clonorchiasis under global climate change.
PMID- 25123069
TI - Four-decade-old mummified umbilical tissue making retrospective molecular
diagnosis of ornithine carbamoyltransferase deficiency.
PMID- 25123070
TI - Factors influencing household uptake of improved solid fuel stoves in low- and
middle-income countries: a qualitative systematic review.
AB - Household burning of solid fuels in traditional stoves is detrimental to health,
the environment and development. A range of improved solid fuel stoves (IS) are
available but little is known about successful approaches to dissemination. This
qualitative systematic review aimed to identify factors that influence household
uptake of IS in low- and middle-income countries. Extensive searches were carried
out and studies were screened and extracted using established systematic review
methods. Fourteen qualitative studies from Asia, Africa and Latin-America met the
inclusion criteria. Thematic synthesis was used to synthesise data and findings
are presented under seven framework domains. Findings relate to user and
stakeholder perceptions and highlight the importance of cost, good stove design,
fuel and time savings, health benefits, being able to cook traditional dishes and
cleanliness in relation to uptake. Creating demand, appropriate approaches to
business, and community involvement, are also discussed. Achieving and sustaining
uptake is complex and requires consideration of a broad range of factors, which
operate at household, community, regional and national levels. Initiatives aimed
at IS scale up should include quantitative evaluations of effectiveness,
supplemented with qualitative studies to assess factors affecting uptake, with an
equity focus.
PMID- 25123071
TI - Vasculogenic mimicry: a new prognostic sign of human osteosarcoma.
AB - Vasculogenic mimicry (VM), a formation of nonendothelial microvascular channels,
has been generally recognized as a new pattern of neovascularization in
aggressive malignancies. However, whether VM is present and clinically
significant in osteosarcoma remains unknown. We identified VM by CD34/periodic
acid-Schiff double staining of osteosarcoma specimens before chemotherapy and
investigated its prognostic implications. Tumors were also immunohistochemically
stained for focal adhesion kinase (FAK) and migration inducing gene 7 (Mig-7) to
determine whether these markers are associated with the occurrence of VM. VM was
found in 15 of 66 osteoblastic-type osteosarcoma samples (22.7%), and the
incidence of VM did not differ with respect to patient sex, age, tumor size,
tumor site, surgical type, or histologic response to preoperative chemotherapy.
However, Kaplan-Meier survival analysis determined that the presence of VM and
the tumor necrosis rate after preoperative chemotherapy are associated with both
the overall survival (P = .011 and P = .040, respectively) and metastasis-free
survival (P = .002 and P = .045, respectively). Furthermore, Cox proportional
hazards analysis showed that the presence of VM and the histologic response to
preoperative chemotherapy were independent indicators for both poor overall
survival (P = .007 and P = .024, respectively) and poor metastasis-free survival
(P = .002 and P = .027, respectively). The expression level of FAK and Mig-7 were
higher in the VM group than the non-VM group (P = .017 and P = .021,
respectively). These results demonstrate the presence of VM in osteoblastic
osteosarcoma and suggest that VM is an unfavorable prognostic factor with FAK and
Mig-7 expressions as a potential mechanism of VM formation in osteosarcoma.
PMID- 25123072
TI - Leukocyte chemotactic factor 2 amyloidosis can be reliably diagnosed by
immunohistochemical staining.
PMID- 25123073
TI - Sclerosing epithelioid fibrosarcoma presenting as intraabdominal sarcomatosis
with a novel EWSR1-CREB3L1 gene fusion.
AB - We report a case of intraabdominal sclerosing epithelioid fibrosarcoma (SEF) with
a t (11;22)(p11.2;q12.2) Ewing sarcoma breakpoint region 1-cAMP-responsive
element-binding protein 3-like 1 translocation. A 43-year old man presented with
massive ascites and shortness of breath. Imaging studies revealed a large
mesenteric-based mass with extensive omental/peritoneal disease. After resection
and cytoreductive surgery, the tumor recurred with metastasis to the lungs; the
patient is still alive with disease. Histologically, there was a uniform
population of epithelioid cells arranged in cords and nests, embedded in a dense
collagenous matrix; no areas of low-grade fibromyxoid sarcoma were identified.
All immunohistochemical markers were nonreactive. Fluorescence in situ
hybridization studies showed rearrangement of Ewing sarcoma breakpoint region 1.
Genomic profiling by clinical grade next-generation sequencing revealed a fusion
gene between intron 11 of Ewing sarcoma breakpoint region 1 (22q12.2) and intron
5 of cAMP-responsive element-binding protein 3-like 1 (11p11.2). This is the
first report of "pure" or true SEF presenting as intraabdominal sarcomatosis with
confirmation of the recently described unique Ewing sarcoma breakpoint region 1
cAMP-responsive element-binding protein 3-like 1 gene fusion in SEF without areas
of low-grade fibromyxoid sarcoma.
PMID- 25123074
TI - Choledochal cysts: a clinicopathologic study of 36 cases with emphasis on the
morphologic and the immunohistochemical features of premalignant and malignant
alterations.
AB - Choledochal cysts (CDCs) are believed to represent a risk factor for the
development of neoplasia. However, the frequency and morphology of neoplastic
changes have not been systematically studied, especially in North America. Our
aims were to study the frequency and morphology of preneoplastic/neoplastic
changes of CDCs. Thirty-six cysts were subjected to clinicopathological analyses.
Metaplasia was found in 14 of 35, of which 9 had biliary intraepithelial
neoplasia (BilIN). Of the 14 with metaplasia, 13 showed pyloric gland; 5,
intestinal; and 2, squamous. BilINs included 6 BilIN-1, 2 BilIN-2, and 2 BilIN-3.
Carcinoma was identified in 5 cases of which 3 were associated with metaplasia
and BilIN. Only 1 of 18 cases without metaplasia had BilIN, and none had
carcinoma (P = .0008). There was a trend toward more BilIN and carcinoma with
intestinal rather than with pyloric gland metaplasia. All cases with metaplasia
or/and BilIN were negative for MUC1. All cases with intestinal metaplasia were
positive for CK20, CDX2, and MUC2, whereas cases with pyloric gland were positive
for MUC6. MUC1, CEA, and B72.3 were positive only in carcinoma. There was a trend
toward increasing p53 and Ki-67 from metaplasia to BilIN to carcinoma. Four of 5
patients with carcinoma died, and one was alive with disease. All others were
free of disease except for one who developed new cysts. CDCs are associated with
a high rate of BilIN (28.5%) and carcinoma (14.3%). CDCs show a sequence of tumor
progression from metaplasia to BilIN and carcinoma.
PMID- 25123075
TI - Leukocyte chemotactic factor 2 amyloidosis cannot be reliably diagnosed by
immunohistochemical staining--reply.
PMID- 25123077
TI - Mimickers of neoplasm on abdominal and pelvic CT.
AB - PURPOSE: The radiologist can encounter benign significant imaging findings on
computed tomography that can be incorrectly interpreted as neoplasm. The authors
review several benign findings and demonstrate several methods to differentiate
these findings from more sinister pathology. CONCLUSION: It is imperative for the
radiologist to be cognizant of and how to correctly identify mimickers of
pathology so that unnecessary interventions and surgeries are avoided.
PMID- 25123076
TI - Colchicine for acute gout.
AB - BACKGROUND: This is an update of a Cochrane review first published in 2006. Gout
is one of the most common rheumatic diseases worldwide. Despite the use of
colchicine as one of the first-line therapies for the treatment of acute gout,
evidence for its benefits and harms is relatively limited. OBJECTIVES: To
evaluate the benefits and harms of colchicine for the treatment of acute gout.
SEARCH METHODS: We searched the following electronic databases from inception to
April 2014: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and
EMBASE. We did not impose any date or language restrictions in the search. We
also handsearched conference proceedings of the American College of Rheumatology
and the European League against Rheumatism (2010 until 2013) and reference lists
of identified studies. We searched the clinical trials register
clinicaltrials.gov and the WHO trials register. SELECTION CRITERIA: We considered
published randomised controlled trials (RCTs) and controlled clinical trials
(CCTs) evaluating colchicine therapy compared with another therapy (active or
placebo) in acute gout. The primary benefit outcome of interest was pain, defined
as a proportion with 50% or greater decrease in pain, and the primary harm
outcome was study participants withdrawal due to adverse events. DATA COLLECTION
AND ANALYSIS: Two authors independently screened search results for relevant
studies, extracted data into a standardised form and assessed the risk of bias of
included studies. We pooled data if deemed to be sufficiently clinically
homogeneous. We assessed the quality of the body of evidence for each outcome
using the GRADE approach. MAIN RESULTS: Two RCTs (124 participants) were included
in this updated review, including one new RCT. We considered one trial to be at
low risk of bias, while we considered the newly included trial to be at unclear
risk of bias. Both trials included a placebo and a high-dose colchicine arm,
although the colchicine regimens varied. In one trial 0.5 mg colchicine was given
every two hours until there was either complete relief of symptoms or toxicity
and the total doses were not specified. In the other trial a total of 4.8 mg
colchicine was given over six hours. The newly identified trial also included a
low-dose colchicine arm (total 1.8 mg over one hour).Based upon pooled data from
two trials (124 participants), there is low-quality evidence that a greater
proportion of people receiving high-dose colchicine experience a 50% or greater
decrease in pain from baseline up to 32 to 36 hours compared with placebo (35/74
in the high-dose colchicine group versus 12/50 in the placebo group (risk ratio
(RR) 2.16, 95% confidence interval (CI) 1.28 to 3.65), with a number needed to
treat to benefit (NNTB) of 4 (95% CI 3 to 12). However, the total number of
adverse events (diarrhoea, vomiting or nausea) is greater in those who receive
high-dose colchicine versus placebo (62/74 in the high-dose colchicine group
versus 11/50 in the placebo group (RR 3.81, 95% CI 2.28 to 6.38), with a number
needed to treat to harm (NNTH) of 2 (95% CI 2 to 5). Only one trial included
reduction of inflammation as part of a composite measure comprising pain,
tenderness, swelling and erythema, each graded on a four-point scale (none 0 to
severe 3) to derive a maximum score for any one joint of 12. They reported the
proportion of people who achieved a 50% reduction in this composite score. Based
upon one trial (43 participants), there was low-quality evidence that more people
in the high-dose colchicine group had a 50% or greater decrease in composite
score from baseline up to 32 to 36 hours than people in the placebo group (11/22
in the high-dose colchicine group versus 1/21 in the placebo group (RR 10.50, 95%
CI 1.48 to 74.38) and 45% absolute difference).Based upon data from one trial
(103 participants), there was low-quality evidence that low-dose colchicine is
more efficacious than placebo with respect to the proportion of people who
achieve a 50% or greater decrease in pain from baseline to 32 to 36 hours (low
dose colchicine 31/74 versus placebo 5/29 (RR 2.43, 95% CI 1.05 to 5.64)), with a
NNTB of 5 (95% CI 2 to 20). There are no additional harms in terms of adverse
events (diarrhoea, nausea or vomiting) with low-dose colchicine compared to
placebo (19/74 and 6/29 respectively (RR 1.24, 95% CI 0.55 to 2.79)).Based upon
data from one trial (126 participants), there is low-quality evidence that there
are no additional benefits in terms of the proportion of people achieving 50% or
greater decrease in pain from baseline up to 32 to 36 hours with high-dose
colchicine compared to low-dose (19/52 and 31/74 respectively (RR 0.87, 95% CI
0.56 to 1.36). However, there were statistically significantly more adverse
events in those who received high-dose colchicine (40/52 versus 19/74 in the low
dose group (RR 3.00, 95% CI 1.98 to 4.54)), with a NNTH of 2 (95% CI 2 to 3).No
trials reported function of the target joint, patient-reported global assessment
of treatment success, health-related quality of life or withdrawals due to
adverse events. We identified no studies comparing colchicine to non-steroidal
anti-inflammatory drugs (NSAIDs) or other active treatments such as
glucocorticoids (by any route). AUTHORS' CONCLUSIONS: Based upon only two
published trials, there is low-quality evidence that low-dose colchicine is
likely to be an effective treatment for acute gout. We downgraded the evidence
because of a possible risk of selection and reporting biases and imprecision.
Both high and low-dose colchicine improve pain when compared to placebo. While
there is some uncertainty around the effect estimates, compared with placebo,
high-dose but not low-dose colchicine appears to result in a statistically
significantly greater number of adverse events. Therefore low-dose colchicine may
be the preferred treatment option. There are no trials about the effect of
colchicine in populations with comorbidities or in comparison with other commonly
used treatments, such as NSAIDs and glucocorticoids.
PMID- 25123078
TI - High-grade undifferentiated sarcomas of the uterus: diagnosis, outcomes, and new
treatment approaches.
AB - High-grade undifferentiated sarcomas (HGUS) are rare malignancies accounting for
6 % of all uterine sarcomas and have a very poor outcome. Histological
classification of HGUS is currently debated as a subgroup with uniform nucleoli,
and frequently YWHAE-FAM22 transcript has been described, constituting a
potential target for new therapies. In localized HGUS, surgery involving total
hysterectomy and bilateral oophorectomy is recommended. Adjuvant radiotherapy has
recently been suggested in a retrospective study to decrease local recurrence and
improve survival versus observation in localized HGUS. In metastatic or recurrent
disease, chemotherapy with doxorubicin with or without ifosfamide constitutes the
standard of care. Gemcitabine plus docetaxel also seems to be an interesting
alternative. Targeted therapies such as pazopanib are now available for soft
tissue sarcomas and so could be proposed for uterine sarcoma patients after first
or second-line chemotherapy in the metastatic phase. Further investigations are
needed to determine their indications and targets. A European Organisation for
Research and Treatment of Cancer (EORTC) randomized trial testing maintenance
therapy with cabozantinib after first-line chemotherapy in HGUS is ongoing.
PMID- 25123080
TI - The role of individual and collective moral disengagement in peer aggression and
bystanding: a multilevel analysis.
AB - This study investigates the relationships between individual and collective moral
disengagement and aggression-related behaviors (peer aggression, defending, and
passive bystanding) among 918 adolescents (55.8% boys; M age = 14.1 years, SD =
1.1). Hierarchical linear modeling showed that, at the individual level,
aggressive behavior was significantly explained by both individual moral
disengagement and student perceived collective moral disengagement, which was
also positively associated with defending. Student perceived collective moral
disengagement moderated the link between individual moral disengagement and peer
aggression. At the class level, classroom collective moral disengagement
explained between-class variability in all the three aggression-related
behaviors. These results extend previous research by demonstrating the role of
collective moral disengagement at the individual and the class levels and have
potential implications for interventions.
PMID- 25123079
TI - Cancer-promoting effects of microbial dysbiosis.
AB - Humans depend on our commensal bacteria for nutritive, immune-modulating, and
metabolic contributions to maintenance of health. However, this commensal
community exists in careful balance that, if disrupted, enters dysbiosis; this
has been shown to contribute to the pathogenesis of colon, gastric, esophageal,
pancreatic, laryngeal, breast, and gallbladder carcinomas. This development is
closely tied to host inflammation, which causes and is aggravated by microbial
dysbiosis and increases vulnerability to pathogens. Advances in sequencing
technology have increased our ability to catalog microbial species associated
with various cancer types across the body. However, defining microbial biomarkers
as cancer predictors presents multiple challenges, and existing studies
identifying cancer-associated bacteria have reported inconsistent outcomes.
Combining metabolites and microbiome analyses can help elucidate interactions
between gut microbiota, metabolism, and the host. Ultimately, understanding how
gut dysbiosis impacts host response and inflammation will be critical to creating
an accurate picture of the role of the microbiome in cancer.
PMID- 25123081
TI - Stress sensitivity interacts with depression history to predict depressive
symptoms among youth: prospective changes following first depression onset.
AB - Predictors of depressive symptoms may differ before and after the first onset of
major depression due to stress sensitization. Dependent stressors, or those to
which characteristics of individuals contribute, have been shown to predict
depressive symptoms in youth. The current study sought to clarify how stressors'
roles may differ before and after the first depressive episode. Adolescents (N =
382, aged 11 to 15 at baseline) were assessed at baseline and every 3 months over
the course of 2 years with measures of stressors and depressive symptoms. Semi
structured interviews were conducted every 6 months to assess for clinically
significant depressive episodes. Hierarchical linear modeling showed a
significant interaction between history of depression and idiographic
fluctuations in dependent stressors to predict prospective elevations of
symptoms, such that dependent stressors were more predictive of depressive
symptoms after onset of disorder. Independent stressors predicted symptoms, but
the strength of the association did not vary by depression history. These results
suggest a synthesis of dependent stress and stress sensitization processes that
might maintain inter-episode depressive symptoms among youth with a history of
clinical depression.
PMID- 25123082
TI - Low-dose decitabine induces MAGE-A expression and inhibits invasion via
suppression of NF-kappaB2 and MMP2 in Eca109 cells.
AB - Decitabine, a demethylating drug, is the first-line treatment for myelodysplastic
syndromes and gains better overall survival, which is based on epigenetic
mechanism. Activated by promoter demethylation, melanoma-associated antigens-A
(MAGE-A), cancer-testis antigens are attractive targets for immunotherapy. Our
purpose was to investigate whether decitabine could show anti-tumor effects for
esophageal cancer and explore its mechanism. In addition, we aimed to examine its
modulation for most MAGE-A members. The results showed the baseline expression
were MAGE-A2, -3,-9, and -10 in Eca109 cells and decitabine (0.5 MUM) could
induce MAGE-A8 and -A4 whereas reduce MAGE-A9 and -A10. Moreover, decitabine (0.5
MUM) inhibited cell proliferation, migration and invasive ability by 15%, 34% and
47.2%, respectively and decreased expressions of NF-kappaB2 and MMP2. Our results
demonstrated that low-dose decitabine induced the expression of MAGE-A8 and -A4,
and inhibited cell invasion through decreasing expression of MMP2 and NF-kappaB2,
which provides possibilities for combing decitabine with immunotherapy targeting
MAGE-A to treat advanced esophageal squamous cell carcinoma.
PMID- 25123083
TI - Superparamagnetic iron oxide nanoparticles impair endothelial integrity and
inhibit nitric oxide production.
AB - Superparamagnetic iron oxide nanoparticles (SPION) are widely used both
clinically and experimentally for diverse in vivo applications, such as contrast
enhancement in magnetic resonance imaging, hyperthermia and drug delivery.
Biomedical applications require particles to have defined physical and chemical
properties, and to be stable in biological media. Despite a suggested low
cytotoxic action, adverse reactions of SPION in concentrations relevant for
biomedical use have not yet been studied in sufficient detail. In the present
work we employed Endorem(r), dextran-stabilized SPION approved as an intravenous
contrast agent, and compared its action to a set of other nanoparticles with
potential for magnetic resonance imaging applications. SPION in concentrations
relevant for in vivo applications were rapidly taken up by endothelial cells and
exhibited no direct cytotoxicity. Electric cell impedance sensing measurements
demonstrated that SPION, but not BaSO4/Gd nanoparticles, impaired endothelial
integrity, as was confirmed by increased intercellular gap formation in
endothelial monolayers. These structural changes induced the subcellular
translocation and inhibition of the cytoprotective and anti-atherosclerotic
enzyme endothelial NO-synthase and reduced NO production. Lipopolysaccharide
induced inflammatory NO production of macrophages was not affected by SPION. In
conclusion, our data suggest that SPION might substantially alter endothelial
integrity and function at therapeutically relevant doses, which are not
cytotoxic.
PMID- 25123084
TI - The influence of social anxiety on the body checking behaviors of female college
students.
AB - Social anxiety and eating pathology frequently co-occur. However, there is
limited research examining the relationship between anxiety and body checking,
aside from one study in which social physique anxiety partially mediated the
relationship between body checking cognitions and body checking behavior (Haase,
Mountford, & Waller, 2007). In an independent sample of 567 college women, we
tested the fit of Haase and colleagues' foundational model but did not find
evidence of mediation. Thus we tested the fit of an expanded path model that
included eating pathology and clinical impairment. In the best-fitting path model
(CFI=.991; RMSEA=.083) eating pathology and social physique anxiety positively
predicted body checking, and body checking positively predicted clinical
impairment. Therefore, women who endorse social physique anxiety may be more
likely to engage in body checking behaviors and experience impaired psychosocial
functioning.
PMID- 25123086
TI - Telomerase reverse transcriptase promoter mutation is an early somatic genetic
alteration in the transformation of premalignant nodules in hepatocellular
carcinoma on cirrhosis.
AB - Genetic determinants of the early steps of carcinogenesis on cirrhosis are still
poorly understood. We aimed to evaluate the occurrence of telomerase reverse
transcriptase (TERT) promoter mutations in the transformation of cirrhotic
nodules into hepatocellular carcinoma (HCC). We analyzed a series of 268 liver
samples, including 96 nodules developed in 58 patients with cirrhosis and 114
additional cirrhosis. All samples were screened for TERT promoter mutations, and
in 31 nodules, for 10 genes recurrently mutated in HCC. Immunohistochemistry
(IHC) analyses were performed for glypican 3, glutamine synthase, and heat shock
protein 70. Six liver pathologists reviewed all the samples. Among The 96
nodules, 88 were firmly diagnosed as low-grade dysplastic nodules (LGDNs; 32
cases), high-grade dysplastic nodules (HGDNs; 16 cases), early HCC (eHCC; 23
cases), or small and progressed HCC in 17 cases. The agreement between the
initial diagnosis from pathological report and the final expert consensus report
was moderate for the diagnosis of benign versus malignant nodules (weighted kappa
= 0.530). TERT promoter mutations were highly related to the step-wise
hepatocarcinogenesis because mutations were identified in 6% of LGDNs, 19% of
HGDNs, 61% of eHCCs, and 42% of small and progressed HCC. TERT promoter mutation
is the most frequent molecular alteration in eHCC given that the IHC criteria for
diagnosis of malignancy were found in only 39% of the cases. TERT promoter
mutation was also the earliest genetic alteration because mutations in 10 other
genes were only identified in 28% of the small and progressed HCC. CONCLUSION:
Frequency of TERT promoter mutations rapidly increases during the different steps
of the transformation of premalignant lesions into HCC on cirrhosis.
Consequently, somatic TERT promoter mutation is a new biomarker predictive of
transformation of premalignant lesions into HCC.
PMID- 25123087
TI - High-throughput continuous flow femtosecond laser-assisted cell optoporation and
transfection.
AB - We present a femtosecond-laser based nanoprocessing system for transient optical
cell membrane poration to allow the introduction of foreign molecules into the
interior of a cell with very high throughput. In the setup, cells flow through a
micro-flow tube for spatial confinement and are simultaneously targeted by fs
laser radiation. Beam-shaping generates a focal geometry along a line which is
scanned across the micro-flow cell to increase the number of reachable cells.
Successful cell membrane poration was observed indirectly by cell transfection
even with cell-light interaction times in the millisecond range. The system was
characterized by experiments with Chinese hamster ovary cells regarding cell
viability, the uptake of extrinsic molecules and cell transfection efficiency.
The continuous flow of cells enables a tremendous increase of cell throughput
compared to previous nonflow approaches by treating millions of cells, although
with only limited efficiency. The setup opens the possibility to realize a
completely automated high-throughput laser-assisted cell-poration system which
could be integrated in lab-on-a-chip devices.
PMID- 25123085
TI - Genetic diversity of porcine group A rotavirus strains in the UK.
AB - Rotavirus is endemic in pig farms where it causes a loss in production. This
study is the first to characterise porcine rotavirus circulating in UK pigs.
Samples from diarrheic pigs with rotavirus enteritis obtained between 2010 and
2012 were genotyped in order to determine the diversity of group A rotavirus
(GARV) in UK pigs. A wide range of rotavirus genotypes were identified in UK
pigs: six G types (VP7); G2, G3, G4, G5, G9 and G11 and six P types (VP4); P[6],
P[7], P[8], P[13], P[23], and P[32]. With the exception of a single P[8] isolate,
there was less than 95% nucleotide identity between sequences from this study and
any available rotavirus sequences. The G9 and P[6] genotypes are capable of
infecting both humans and pigs, but showed no species cross-over within the UK as
they were shown to be genetically distinct, which suggested zoonotic transmission
is rare within the UK. We identified the P[8] genotype in one isolate, this
genotype is almost exclusively found in humans. The P[8] was linked to a human
Irish rotavirus isolate in the same year. The discovery of human genotype P[8]
rotavirus in a UK pig confirms this common human genotype can infect pigs and
also highlights the necessity of surveillance of porcine rotavirus genotypes to
safeguard human as well as porcine health.
PMID- 25123088
TI - Genotoxic, epigenetic, and transcriptomic effects of tamoxifen in mouse liver.
AB - Tamoxifen is a non-steroidal anti-estrogenic drug widely used for the treatment
and prevention of breast cancer in women; however, there is evidence that
tamoxifen is hepatocarcinogenic in rats, but not in mice. Additionally, it has
been reported that tamoxifen may cause non-alcoholic fatty liver disease (NAFLD)
in humans and experimental animals. The goals of the present study were to (i)
investigate the mechanisms of the resistance of mice to tamoxifen-induced
hepatocarcinogenesis, and (ii) clarify effects of tamoxifen on NAFLD-associated
liver injury. Feeding female WSB/EiJ mice a 420 p.p.m. tamoxifen-containing diet
for 12 weeks resulted in an accumulation of tamoxifen-DNA adducts, (E)-alpha
(deoxyguanosin-N(2)-yl)-tamoxifen (dG-TAM) and (E)-alpha-(deoxyguanosin-N(2)-yl)
N-desmethyltamoxifen (dG-DesMeTAM), in the livers. The levels of hepatic dG-TAM
and dG-DesMeTAM DNA adducts in tamoxifen-treated mice were 578 and 340
adducts/108 nucleotides, respectively, while the extent of global DNA and
repetitive elements methylation and histone modifications did not differ from the
values in control mice. Additionally, there was no biochemical or
histopathological evidence of NAFLD-associated liver injury in mice treated with
tamoxifen. A transcriptomic analysis of differentially expressed genes
demonstrated that tamoxifen caused predominantly down-regulation of hepatic lipid
metabolism genes accompanied by a distinct over-expression of the lipocalin 13
(Lcn13) and peroxisome proliferator receptor gamma (Ppargamma), which may prevent
the development of NAFLD. The results of the present study demonstrate that the
resistance of mice to tamoxifen-induced liver carcinogenesis may be associated
with its ability to induce genotoxic alterations only without affecting the
cellular epigenome and an inability of tamoxifen to induce the development of
NAFLD.
PMID- 25123091
TI - Azavinylidenephosphoranes: a class of cyclic push-pull carbenes.
AB - The synthesis of a novel family of cyclic push-pull carbenes, namely,
azavinylidene phosphoranes, is described. The methodology is based on a formal
[3+2] cycloaddition between terminal alkynes and phosphine-imines followed by an
oxidation/deprotonation step. Carbenes 6, obtained by simple deprotonation,
exhibit typical transient carbene reactivity like the intramolecular C?H
insertion reaction and a pronounced ambiphilic character exemplified by [2+1]
cycloaddition with electron-poor methyl acrylate. Owing to the cyclic structure,
carbenes 6 also exhibit an excellent coordination ability toward transition
metals. Rh(I) complex 10 was obtained in excellent yield and was fully
characterized by multinuclear NMR spectroscopy and X-ray crystallography. The
corresponding Rh(I) -carbonyl complex was also prepared; this indicates that
carbenes 6 belong to the strongest sigma-donating ligands to date. DFT
calculations confirmed the high sigma-donation ability of 6 and their
classification as push-pull carbenes with a relatively small singlet-triplet
energy gap of 23.2-24.3 kcal mol(-1) .
PMID- 25123090
TI - [The posterocentral approach to the posterior tibial plateau].
AB - OBJECTIVE: An anatomically preformed approach to the posterior tibial plateau is
described. In avulsion fractures of the posterior cruciate ligament (PCL), the
aim is to restore stability of the knee joint with functional treatment, while in
posterior shearing tibial plateau fractures the aim is to restore anatomical
dorsal alignment of the tibia. INDICATIONS: Avulsion fracture the PCL, posterior
shearing tibial plateau fracture. CONTRAINDICATIONS: Knee infection, compartment
syndrome, joint instability, and osteoarthritis in avulsion fractures of the PCL.
OPERATION TECHNIQUE: Supine position, L-shaped skin incision, dissection of the
fascia, protection of the sural nerve, separation of the gastrocnemial heads,
identification of the neurovascular bundle, retraction of the gastrocnemial
heads. Fixation of the bony avulsion using screws. In tibial plateau fractures,
dissection of the soleus and popliteus muscle, fracture reduction, and plate
fixation. POSTOPERATIVE MANAGEMENT: Due to the approach no specific treatment
necessary. PCL: functional treatment, with knee brace full weight bearing
possible, without 20 kg weight bearing using crutches for 4-6 weeks, tibia: CT
for postoperative result and planning of the ventral osteosynthesis after about 5
days, then weight bearing 20 kg and functional treatment for 8-12 weeks. RESULTS:
A total of 33 patients were operated using a posterocentral approach, 22 had a
posterior shearing tibial plateau fracture, and 11 an avulsion fracture of the
PCL. Temporary hypesthesia around the scar, at the lateral foot, and lateral
lower leg were observed in 3 patients, each having one (area supplied by the
sural nerve). In 3 cases screw tips at the anterior proximal tibia were palpable.
The posterocentral approach reveals a low complication rate due to the anatomical
approach.
PMID- 25123089
TI - Dye-loaded ferritin nanocages for multimodal imaging and photothermal therapy.
AB - Multimodal imaging-guided photothermal therapy (PTT), for the therapy of cancer,
based on a ferritin (FRT) nanocage loaded with the near-infrared dye IR820
(designated DFRT) is demonstrated. The dual roles of DFRT (in imaging and PTT)
are successfully balanced by using two different excitation wavelengths: 550 nm
for high quantum-yield fluorescence imaging on the one hand and 808 nm for
photoacoustic imaging and PTT with high photothermal conversion efficiency on the
other.
PMID- 25123092
TI - A specialized post anaesthetic care unit improves fast-track management in
cardiac surgery: a prospective randomized trial.
AB - INTRODUCTION: Fast-track treatment in cardiac surgery has become the global
standard of care. We compared the efficacy and safety of a specialised post
anaesthetic care unit (PACU) to a conventional intensive care unit (ICU) in
achieving defined fast-track end-points in adult patients after elective cardiac
surgery. METHODS: In a prospective, single blinded, randomized study, 200 adult
patients undergoing elective cardiac surgery (coronary artery bypass graft
(CABG), valve surgery or combined CABG and valve surgery), were selected to
receive their postoperative treatment either in the ICU (n = 100), or in the PACU
(n = 100). Patients who, at the time of surgery, were in cardiogenic shock,
required renal dialysis, or had an additive EuroSCORE of more than 10 were
excluded from the study. The primary end points were: time to extubation (ET),
and length of stay in the PACU or ICU (PACU/ICU LOS respectively). Secondary end
points analysed were the incidences of: surgical re-exploration, development of
haemothorax, new onset cardiac arrhythmia, low cardiac output syndrome, need for
cardio-pulmonary resuscitation, stroke, acute renal failure, and death. RESULTS:
Median time to extubation was 90 [50; 140] min in the PACU vs. 478 [305; 643] min
in the ICU group (P < 0.001). Median length of stay in PACU was 3.3 [2.7; 4.0]
hours vs. 17.9 [10.3; 24.9] hours in the ICU (P < 0.001). Of the adverse events
examined, only the incidence of new onset cardiac arrhythmia (25 in PACU vs. 41
in ICU, P = 0.02) was statistically different between groups. CONCLUSIONS:
Treatment in a specialised PACU rather than an ICU, after elective cardiac
surgery leads to earlier extubation and quicker discharge to a step down unit,
without compromising patient safety. TRIAL REGISTRATION: ISRCTN71768341.
Registered 11 March 2014.
PMID- 25123095
TI - Asymmetric Michael addition/intramolecular cyclization catalyzed by bifunctional
tertiary amine-squaramides: construction of chiral 2-amino-4H-chromene-3
carbonitrile derivatives.
AB - The efficient asymmetric Michael addition/intramolecular cyclization of
malononitrile with dienones catalyzed by a chiral bifunctional tertiary amine
squaramide catalyst for the synthesis of chiral 2-amino-4H-chromene-3
carbonitrile derivatives was developed. The corresponding products were obtained
in good to excellent yields (up to 99%) with excellent enantioselectivities (up
to 98% ee) for most of the bisarylidenecyclopentanones.
PMID- 25123096
TI - Transport phenomena in nanoporous materials.
AB - Diffusion, that is, the irregular movement of atoms and molecules, is a universal
phenomenon of mass transfer occurring in all states of matter. It is of equal
importance for fundamental research and technological applications. The present
review deals with the challenges of the reliable observation of these phenomena
in nanoporous materials. Starting with a survey of the different variants of
diffusion measurement, it highlights the potentials of "microscopic" techniques,
notably the pulsed field gradient (PFG) technique of NMR and the techniques of
microimaging by interference microscopy (IFM) and IR microscopy (IRM).
Considering ensembles of guest molecules, these techniques are able to directly
record mass transfer phenomena over distances of typically micrometers. Their
concerted application has given rise to the clarification of long-standing
discrepancies, notably between microscopic equilibrium and macroscopic non
equilibrium measurements, and to a wealth of new information about molecular
transport under confinement, hitherto often inaccessible and sometimes even
unimaginable.
PMID- 25123093
TI - Shedding of Salmonella in single age caged commercial layer flock at an early
stage of lay.
AB - The shedding of Salmonella in a single age commercial egg layer flock was
investigated at the onset of lay (18weeks) followed by two longitudinal samplings
at 24 and 30weeks. At the age of 18weeks, when the first sampling was performed,
the prevalence of Salmonella in faeces was 82.14% whereas all egg belt and dust
samples were Salmonella positive by culture method. In later samplings, at the
age of 24 and 30weeks, the prevalence of Salmonella in faeces was significantly
reduced (p<0.001) to 38.88% and 12.95% respectively, however all egg belt and
dust samples remained positive by culture method. The prevalence of Salmonella in
faeces collected from the low tier cages was significantly higher (p=0.009) as
compared with samples from the high tier cages. In all types of samples processed
by culture method, S. Mbandaka was the most frequently (54.40%) isolated serovar
followed by S. Worthington (37.60%), S. Anatum (0.8%), and S. Infantis (0.8%).
All samples were also tested by real-time PCR method. The observed agreement
between culture method and real-time PCR in detecting Salmonella-positive dust
and egg belt samples was 100%. There was almost perfect agreement (observed
agreement=99.21%) for the detection of Salmonella-positive eggshells. Observed
agreement between culture method and real-time PCR for detecting Salmonella
positive shoe cover and faecal samples was, however, moderate (80%) and low
(54.27%) respectively. Real-time PCR results showed that there was a significant
increase in the load of Salmonella on egg belt, dust and shoe cover samples at
the 24 and 30weeks of lay as compared to the 18weeks of lay. Real-time PCR
provided a more rapid and reliable method of detection of Salmonella on all dry
sample types whereas the traditional culture method proved much more reliable
when trying to detect Salmonella in wet faecal samples.
PMID- 25123094
TI - Modeling of topology-dependent neural network plasticity induced by activity
dependent electrical stimulation.
AB - Activity-dependent electrical stimulation can induce cerebrocortical
reorganization in vivo by activating brain areas using stimulation derived from
the statistics of neural or muscular activity. Due to the nature of synaptic
plasticity, network topology is likely to influence the effectiveness of this
type of neuromodulation, yet its effect under different network topologies is
unclear. To address this issue, we simulated small-scale three-neuron networks to
explore topology-dependent network plasticity. The induced neuroplastic changes
were evaluated by network coherence and unit-pair mutual information measures. We
demonstrated that involvement of monosynaptic feedforward and reciprocal
connections is more likely to lead to persistent decreased network coherence and
increased network mutual information independent of the global network topology.
On the contrary, disynaptic feedforward connections exhibit heterogeneous
coherence and unit-pair mutual information sensitivity that depends strongly upon
the network context.
PMID- 25123097
TI - Allelic-specific expression in relation to Bombyx mori resistance to Bt toxin.
AB - Understanding the mechanism of Bt resistance is one of the key elements of the
effective application of Bt in pest control. The lepidopteran model insect, the
silkworm, demonstrates qualities that make it an ideal species to use in
achieving this understanding. We screened 45 strains of silkworm (Bombyx mori)
using a Cry1Ab toxin variant. The sensitivity levels of the strains varied over a
wide range. A resistant strain (P50) and a phylogenetically related susceptible
strain (Dazao) were selected to profile the expressions of 12 Bt resistance
related genes. The SNPs in these genes were detected based on EST analysis and
were validated by allelic-specific PCR. A comparison of allelic-specific
expression between P50 and Dazao showed that the transcript levels of
heterozygous genes containing two alleles rather than an imbalanced allelic
expression contribute more to the resistance of P50 against Bt. The responses of
the allelic-specific expression to Bt in hybrid larvae were then investigated.
The results showed that the gene expression pattern of an ATP-binding cassette
transporter C2 (ABCC2) and an aminopeptidase N (APN3), changed in an allelic
specific manner, with the increase of the resistant allele expression correlated
with larval survival. The results suggest that a trans-regulatory mechanism in
ABCC2 and APN3 allelic-specific expression is involved in the insect's response
to the Bt toxin. The potential role of allelic-specific gene regulation in insect
resistance to Bt toxins is discussed.
PMID- 25123099
TI - Lanthanide doped nanoparticles as remote sensors for magnetic fields.
AB - We report the effect of magnetic fields (MFs) on emission Eu-doped NaYF4
nanoparticles. A notable shift in the position of emission bands and the
suppressed emission intensity are observed with the MF. These magnetic-optical
interactions are explained in terms of the Zeeman effect, enhanced cross
relaxation rate and change of site symmetry.
PMID- 25123098
TI - [Symptom control and place of death in palliative cancer patients in primary
care. Results of the controlled PAMINO evaluation study].
AB - BACKGROUND: The care of patients at the end of life focuses on preservation of
the quality of life, symptom control and fulfillment of the preferred place of
death. Only few care and outcome-related data for primary palliative care in
Germany are available; therefore, the objective was to examine the quality of
life, symptom control and place of death of patients with palliative treatment by
general practitioners (GP). MATERIAL AND METHODS: The study is part of the PAMINO
project, a non-randomized, controlled trial evaluating the effectiveness of
continuing medical education for GPs (>= 40 h) in palliative care
(ISRCTN78021852). Cancer patients with an estimated life expectancy of less than
6 months were recruited by GPs with (PG) or without (CG) continuing education and
documented the diagnosis, medication based on the hospice and palliative care
collation ( Hospiz- und Palliativ-Erfassung, HOPE) core documentation and the
preferred place of death. Patients rated their symptom burden and health-related
quality of life using the quality of life questionnaire (QLQ-C15-PAL). Baseline
(t0) data at enrollment and the last individual (t1) assessment were used for the
analysis. RESULTS: Data of 68 patients (PG: n = 43, CG: n = 25, mean age 69.2 +/-
12 years, average time since cancer diagnosis 14 months) were available at t0 and
t1 (mean period 4.0 +/- 2.1 months). Physical function decreased while emotional
functioning remained stable. Patient-perceived pain did not increase; however,
GPs intensified the pain therapy. The PGs prescribed non-opioid analgesics more
frequently than CGs. During the observation period 59 patients died of which 40
out of 48 (83 %) as preferred at home. CONCLUSIONS: Stable emotional functioning,
good symptom control in cancer patients at the end of life and the high rate of
dying at home as preferred suggest that GPs with specific training can ensure
high-quality general palliative care.
PMID- 25123100
TI - Median and quantile tests under complex survey design using SAS and R.
AB - Techniques for conducting hypothesis testing on the median and other quantiles of
two or more subgroups under complex survey design are limited. In this paper, we
introduce programs in both SAS and R to perform such a test. A detailed
illustration of the computations, macro variable definitions, input and output
for the SAS and R programs are also included in the text. Urinary iodine data
from National Health and Nutrition Examination Survey (NHANES) are used as
examples for comparing medians between females and males as well as comparing the
75th percentiles among three salt consumption groups.
PMID- 25123101
TI - Event-driven, pattern-based methodology for cost-effective development of
standardized personal health devices.
AB - Experiences applying standards in personal health devices (PHDs) show an inherent
trade-off between interoperability and costs (in terms of processing load and
development time). Therefore, reducing hardware and software costs as well as
time-to-market is crucial for standards adoption. The ISO/IEEE11073 PHD family of
standards (also referred to as X73PHD) provides interoperable communication
between PHDs and aggregators. Nevertheless, the responsibility of achieving
inexpensive implementations of X73PHD in limited resource microcontrollers falls
directly on the developer. Hence, the authors previously presented a methodology
based on patterns to implement X73-compliant PHDs into devices with low-voltage
low-power constraints. That version was based on multitasking, which required
additional features and resources. This paper therefore presents an event-driven
evolution of the patterns-based methodology for cost-effective development of
standardized PHDs. The results of comparing between the two versions showed that
the mean values of decrease in memory consumption and cycles of latency are
11.59% and 45.95%, respectively. In addition, several enhancements in terms of
cost-effectiveness and development time can be derived from the new version of
the methodology. Therefore, the new approach could help in producing cost
effective X73-compliant PHDs, which in turn could foster the adoption of
standards.
PMID- 25123102
TI - Bayesian bivariate generalized Lindley model for survival data with a cure
fraction.
AB - The cure fraction models have been widely used to analyze survival data in which
a proportion of the individuals is not susceptible to the event of interest. In
this article, we introduce a bivariate model for survival data with a cure
fraction based on the three-parameter generalized Lindley distribution. The joint
distribution of the survival times is obtained by using copula functions. We
consider three types of copula function models, the Farlie-Gumbel-Morgenstern
(FGM), Clayton and Gumbel-Barnett copulas. The model is implemented under a
Bayesian framework, where the parameter estimation is based on Markov Chain Monte
Carlo (MCMC) techniques. To illustrate the utility of the model, we consider an
application to a real data set related to an invasive cervical cancer study.
PMID- 25123103
TI - Geometric and electronic properties of edge-decorated graphene nanoribbons.
AB - Edge-decorated graphene nanoribbons are investigated with the density functional
theory; they reveal three stable geometric structures. The first type is a
tubular structure formed by the covalent bonds of decorating boron or nitrogen
atoms. The second one consists of curved nanoribbons created by the dipole-dipole
interactions between two edges when decorated with Be, Mg, or Al atoms. The final
structure is a flat nanoribbon produced due to the repulsive force between two
edges; most decorated structures belong to this type. Various decorating atoms,
different curvature angles, and the zigzag edge structure are reflected in the
electronic properties, magnetic properties, and bonding configurations. Most of
the resulting structures are conductors with relatively high free carrier
densities, whereas a few are semiconductors due to the zigzag-edge-induced anti
ferromagnetism.
PMID- 25123104
TI - Platelet-to-lymphocyte ratio for early diagnosis of celiac disease.
PMID- 25123106
TI - Tetralogy of Fallot with coronary artery to pulmonary artery fistula.
PMID- 25123108
TI - Cricothyroid onabotulinum toxin A injection to avert tracheostomy in bilateral
vocal fold paralysis.
AB - IMPORTANCE: More than half of children with bilateral vocal fold paralysis
require a tracheostomy for airway management. We report an innovative, minimally
invasive approach consisting of onabotulinum toxin A injection into the
cricothyroid muscles. OBSERVATIONS: Onabotulinum toxin A was injected under
direct vision into the cricothyroid muscles of 6 pediatric patients with
bilateral abductor vocal fold paralysis. None of the patients had fold fixation
on laryngoscopy performed at the time of the injection. All patients had a
documented increase in airway patency as visualized on flexible laryngoscopy
within days after injection. This procedure successfully averted a tracheostomy
in 5 patients and permitted decannulation of the sixth patient. CONCLUSIONS AND
RELEVANCE: Onabotulinum toxin A injection into the cricothyroid muscles leads to
an increase in the glottic space, providing an adequate airway. Onabotulinum
toxin A injection in the cricothyroid muscles could be offered as a safe,
effective, noninvasive first-line option for patients with bilateral vocal fold
paralysis.
PMID- 25123105
TI - Mice selected for extremes in stress reactivity reveal key endophenotypes of
major depression: a translational approach.
AB - Clear evidence has linked dysregulated hypothalamus-pituitary-adrenocortical
(HPA) axis function to the aetiology and pathophysiology of major depression
(MD), as observed in the majority of patients. Increased stress reactivity and
hyperactivity of the HPA axis seem characteristic for psychotic/melancholic
depression, while the atypical subtype of depression has been connected with the
opposing phenotypes. However, the underlying molecular-genetic mechanisms are
poorly understood. In the present study, mouse lines selectively bred for
extremes in stress reactivity (SR), i.e. presenting high (HR) or low (LR)
corticosterone secretion in response to stressors, were used to characterise the
molecular alterations on all levels of the HPA axis. Results were contrasted with
clinical phenotypes of MD patients from the Munich Antidepressant Response
Signature project, stratified according to their cortisol response in the Dex/CRH
test. Distinct differences between HR and LR mice were found in the expression of
HPA axis-related genes in the adrenals, pituitary and selected brain areas.
Moreover, HR animals presented an enhanced adrenal sensitivity, increased stress
induced neuronal activation in the PVN and an overshooting Dex/CRH test response,
whereas LR animals showed a blunted response in these paradigms. Interestingly,
analogous neuroendocrine, morphometric, psychopathological and behavioural
differences were observed between the respective high and low HPA axis responder
groups of MD patients. Our findings suggests that (i) the SR mouse model can
serve as a valuable tool to elucidate HPA axis-related mechanisms underlying
affective disorders and (ii) a stratification of MD patients according to their
HPA axis-related neuroendocrine function should be considered for clinical
research and treatment.
PMID- 25123107
TI - Risk and information evaluation of prioritized genes for complex traits:
application to bipolar disorder.
AB - Many susceptibility genes for complex traits were identified without conclusive
findings. There is a strong need to integrate rapidly accumulated genomic data
from multi-dimensional platforms, and to conduct risk evaluation for potential
therapeutic and diagnostic usages. We set up an algorithm to computationally
search for optimal weight-vector for various data sources, while minimized
potential noises. Through gene-prioritization framework, combined scores for the
resulting prioritized gene-set were calculated using a genome-wide association
(GWA) dataset, following with evaluation using weighted genetic risk score and
risk-attributed information using an independent GWA dataset. The significance of
association of GWA data was corrected for gene length. Enriched functional
pathways were identified for the prioritized gene-set using the Gene Ontology
analysis. We illustrated our framework with bipolar disorder. 233 prioritized
genes were identified from 10,830 candidates that curated from six platforms. The
prioritized genes were significantly enriched (P(adjusted) < 1 * 10(-5)) in 18
biological functions and molecular mechanisms including membrane, synaptic
transmission, transmission of nerve impulse, integral to membrane, and plasma
membrane. Our risk evaluation demonstrated higher weighted genetic risk score in
bipolar patients than controls (P-values ranged from 0.002 to 3.8 * 10(-6)).
Substantial risk-information (71%) was extracted from prioritized genes for
bipolar illness than other candidate-gene sets. Our evidence-based prioritized
gene-set provides opportunity to explore the complex network and to conduct
follow-up basic and clinical studies for complex traits.
PMID- 25123109
TI - Reversible Pisa syndrome associated to subdural haematoma: case-report.
AB - BACKGROUND: Pisa Syndrome or Pleurothotonus is a relatively rare truncal
dystonia, characterized by tonic flexion of the trunk and head to one side with
slight rotation of the body. Since frequently associated to specific drugs such
as antipsychotics and cholinesterase inhibitors or to Parkinson Disease, a
pathophysiological role of cholinergic-dopaminergic imbalance has been suggested.
We report here the first case of Pisa Syndrome due to an extracerebral pathology
as subdural haematoma. CASE PRESENTATION: A hypertensive patient was admitted to
Our Department for subacute onset of tonic flexion and slight rotation of the
trunk associated to progressive motor deficit in left upper limb after a mild
head trauma without loss of consciousness occurred around three month before. No
previous or current pharmacological interventions with antidepressant,
neuroleptic or anticholinergic drugs were anamnestically retrieved. Familiar and
personal history was negative for neurological disorders other than acute
cerebrovascular diseases. Acutely performed cerebral MRI with DWI showed a
voluminous right subdural haematoma with mild shift of median line. After
surgical evacuation, both motor deficit and truncal dystonia were dramatically
resolved. At one-year follow up, the patient did not develop any extrapyramidal
and cognitive signs or symptoms. CONCLUSIONS: According to many Authors, the
occurrence of truncal dystonia during several pharmacologic treatments and
neurodegenerative disorders (such as Alzheimer disease and parkinsonian
syndromes) supported the hypothesis that a complex dysregulation of multiple
neurotransmitter systems are involved. We suggest a possible role of basal
ganglia compression in pathogenesis of truncal dystonia by means of thalamo
cortical trait functional disruption and loss of proprioceptive integration. A
further contribution of the subcortical structure displacement that alters motor
cortex connectivity to basal ganglia may be postulated.
PMID- 25123111
TI - "Neuroendocrine adenoma of the middle ear with the history of otitis media and
carcinoma of the cheek: a case report".
AB - BACKGROUND: Neuroendocrine adenomas of the middle ear are rare benign tumors
deriving from middle ear mucosal cell with both neuroendocrine and epithelial
properties. Approximately one hundred cases have been reported in the literature.
Here we report a patient with neuroendocrine adenoma of the middle ear with the
history of otitis media; the patient earlier had received radiotherapy for the
treatment of basal cell carcinoma. CASE PRESENTATION: A 49- year- old Saudi man
presented with a progressive hearing loss and fullness in the left ear with the
history of otitis media for which he had undergone myringotomy and ventilating
tubes insertion. Earlier at the age of 45 years this patient was given
radiotherapy for the treatment of basal cell carcinoma in his cheek. The otoscopy
showed a protruded external ear mass obscuring the tympanic membrane. Microscopy
and histological examination suggested an endocrine adenoma of the middle ear.
The computerized tomography scan of the temporal bone showed an extensive soft
tissue mass without any osteolysis. Histological and immunohistochemical
examination following surgical excision confirmed the diagnosis of neuroendocrine
adenoma of the middle ear. CONCLUSION: A rare case of neuroendocrine adenoma of
the middle ear with earlier history of otitis media and carcinoma of the cheek is
presented here. Surgical excision of mass resulted in uneventful recovery.
Although the etiologic factors leading to the disease is far from clear, the role
of radiotherapy given for the treatment of basal cell carcinoma may not be ruled
out.
PMID- 25123110
TI - Functional outcome in people at high risk for psychosis predicted by thalamic
glutamate levels and prefronto-striatal activation.
AB - Little is known about the neurobiological factors that determine functional
outcome in people at high risk for psychosis. We use multimodal neuroimaging to
investigate whether cortical responses during a cognitive task and thalamic
glutamate levels were associated with subsequent functional outcome. Sixty
subjects participated: 27 healthy controls (CTRL) and 33 at ultrahigh risk (UHR)
for psychosis. At baseline, cortical responses during a verbal fluency task were
measured using functional Magnetic Resonance Imaging (fMRI) and proton Magnetic
Resonance Spectroscopy (1H-MRS) was used to measure thalamic glutamate levels.
The UHR subjects were then followed clinically for a mean duration of 18 months,
and subdivided into "good" and "poor" functional outcome subgroups according to
their Global Assessment of Function score at follow-up. UHR subjects with a poor
functional outcome showed greater cortical and subcortical activation than UHR
subjects with a good functional outcome. They also had lower levels of thalamic
glutamate and showed a negative relationship between thalamic glutamate levels
and prefrontal-striatal activation that was not present in the good functional
outcome or control groups. In people at high risk for psychosis, their subsequent
level of functioning may depend on the extent to which neurophysiological and
neurochemical function is perturbed when they first present to clinical services.
PMID- 25123112
TI - An eight-year epidemiologic study based on baculovirus-expressed type-specific
spike proteins for the differentiation of type I and II feline coronavirus
infections.
AB - BACKGROUND: Feline infectious peritonitis (FIP) is a fatal disease caused by
feline coronavirus (FCoV). FCoVs are divided into two serotypes with markedly
different infection rates among cat populations around the world. A baculovirus
expressed type-specific domain of the spike proteins of FCoV was used to survey
the infection of the two viruses over the past eight years in Taiwan. RESULTS: An
immunofluorescence assay based on cells infected with the recombinant viruses
that was capable of distinguishing between the two types of viral infection was
established. A total of 833 cases from a teaching hospital was surveyed for
prevalence of different FCoV infections. Infection of the type I FCoV was
dominant, with a seropositive rate of 70.4%, whereas 3.5% of cats were infected
with the type II FCoV. In most cases, results derived from serotyping and
genotyping were highly agreeable. However, 16.7% (4/24) FIP cats and 9.8% (6/61)
clinically healthy cats were found to possess antibodies against both viruses.
Moreover, most of the cats (84.6%, 22/26) infected with a genotypic untypable
virus bearing a type I FCoV antibody. CONCLUSION: A relatively simple serotyping
method to distinguish between two types of FCoV infection was developed. Based on
this method, two types of FCoV infection in Taiwan was first carried out. Type I
FCoV was found to be predominant compared with type II virus. Results derived
from serotyping and genotyping support our current understanding of evolution of
disease-related FCoV and transmission of FIP.
PMID- 25123113
TI - Characterization of newly gained introns in Daphnia populations.
AB - As one of the few known species in an active phase of intron proliferation, the
microcrustacean Daphnia pulex is an especially attractive system for
interrogating the gain and loss of introns in natural populations. In this study,
we used a comparative population-genomic approach to identify and characterize 90
recently gained introns in this species. Molecular clock analyses indicate that
these introns arose between 3.9 * 10(5) and 1.45 * 10(4) years ago, with a spike
in intron proliferation approximately 5.2 * 10(4) to 1.22 * 10(5) years ago.
Parallel gains at homologous positions contribute to 47.8% (43/90) of discovered
new introns. A disproportionally large number of new introns were found in
historically isolated populations in Oregon. Nonetheless, derived, intron-bearing
alleles were also identified in a wide range of geographic locations, suggesting
intron gain and, to a lesser degree, intron loss are important sources of genetic
variation in natural populations of Daphnia. A majority (55/90 or 61.1%) of the
identified neointrons have associated internal direct repeats with lengths and
compositions that are unlikely to occur by chance, suggesting repeated bouts of
staggered double-strand breaks (DSBs) during their evolution. Accordingly,
internal, staggered DSBs may contribute to a passive trend toward increased
length and sequence diversity in nascent introns.
PMID- 25123115
TI - "We are supposed to take care of it": a qualitative examination of care and
repair behaviour of long-lasting, insecticide-treated nets in Nasarawa State,
Nigeria.
AB - BACKGROUND: The longevity of long-lasting insecticidal nets (LLIN) under field
conditions has important implications for malaria vector control. The behaviour
of bed net users, including net care and repair, may protect or damage bed nets
and impact the physical integrity of nets. However, this behaviour, and the
motivating and inhibiting factors, is not well understood. METHODS: Qualitative
research methods were used to examine behaviour, attitudes and norms around
damage, care and repair of LLINs. Eighteen in-depth interviews (IDI) and six
focus group discussions (FGD) were conducted with LLIN users in two local
government areas of Nasarawa State, Nigeria. A brief background questionnaire
with the 73 participants prior to IDIs or FGDs collected additional data on
demographics, net use, and care and repair behaviour. RESULTS: Respondents cited
that the major causes of damage to bed nets are primarily children, followed by
rodents, everyday handling that is not gentle, and characteristics of sleeping
spaces. Caring for nets was perceived as both preventing damage by careful
handling and keeping the net clean, which may lead to over-washing of LLINs.
Repairing a damaged net was considered something that net users should do and the
responsibility of adults in the household. Despite this, reported frequency of
net repair was low (18%). Motivations for taking care of and repairing nets
centred around caring for one's family, avoiding mosquito bites, saving money,
and maintaining the positive opinion of others by keeping a clean and intact net.
Barriers to net care and repair related to time availability and low perceived
value of bed nets or of one's health. CONCLUSION: This study provides novel and
valuable insights on the perceptions and attitudes of LLIN users in Nasarawa,
Nigeria on the durability of bed nets, how to care for and repair nets, and for
what reasons. Communication around net care should stress proper daily storage of
nets, regular net inspections, prompt repairs, and clarify misconceptions about
proper washing frequency and technique. These messages should include compelling
motivators, such as local social norms of household hygiene.
PMID- 25123114
TI - The transcriptome of Nacobbus aberrans reveals insights into the evolution of
sedentary endoparasitism in plant-parasitic nematodes.
AB - Within the phylum Nematoda, plant-parasitism is hypothesized to have arisen
independently on at least four occasions. The most economically damaging plant
parasitic nematode species, and consequently the most widely studied, are those
that feed as they migrate destructively through host roots causing necrotic
lesions (migratory endoparasites) and those that modify host root tissue to
create a nutrient sink from which they feed (sedentary endoparasites). The false
root-knot nematode Nacobbus aberrans is the only known species to have both
migratory endoparasitic and sedentary endoparasitic stages within its life cycle.
Moreover, its sedentary stage appears to have characteristics of both the root
knot and the cyst nematodes. We present the first large-scale genetic resource of
any false-root knot nematode species. We use RNAseq to describe relative
abundance changes in all expressed genes across the life cycle to provide
interesting insights into the biology of this nematode as it transitions between
modes of parasitism. A multigene phylogenetic analysis of N. aberrans with
respect to plant-parasitic nematodes of all groups confirms its proximity to both
cyst and root-knot nematodes. We present a transcriptome-wide analysis of both
lateral gene transfer events and the effector complement. Comparing parasitism
genes of typical root-knot and cyst nematodes to those of N. aberrans has
revealed interesting similarities. Importantly, genes that were believed to be
either cyst nematode, or root-knot nematode, "specific" have both been identified
in N. aberrans. Our results provide insights into the characteristics of a common
ancestor and the evolution of sedentary endoparasitism of plants by nematodes.
PMID- 25123117
TI - Predictors of long-term effect from education and exercise in patients with knee
and hip pain.
AB - INTRODUCTION: Education and exercise are poorly implemented in osteoarthritis
care. The purpose of the present study was to identify predictors of
effectiveness at one year from education and exercise in patients with knee or
hip pain in clinical practice. MATERIAL AND METHODS: Good Life with Arthritis in
Denmark is an implementation initiative consisting of education and 12 sessions
of neuromuscular exercise delivered by trained physiotherapists. Pain (visual
analogue scale 0-100) and quality of life (EQ-5D) were assessed at baseline and
after three and 12 months. Changes in outcome from baseline to one year were
dependent variables in regression analyses, while changes from baseline to 3
months and absolute results at three months in physical performance (30-second
chair stand test) and self-efficacy were predictor variables. RESULTS: A total of
79/82 patients completed the one-year follow-up. Improvements in pain and EQ-5D
at three months were maintained at one year (p < 0.006). Change in self-efficacy
from baseline to three months (Beta = -0.369) and 30-second chair stand test
(Beta = -0.251) and self-efficacy at three months (Beta = -0.492) were predictors
of one-year improvement in pain (p < 0.05). Furthermore, self-efficacy at three
months (Beta = 0.304) was a predictor of one-year improvement in EQ-5D (p =
0.01). CONCLUSION: The identified predictors highlight the importance of
combining education and exercise. This study indicates that good long-term
treatment results are achievable in clinical practice.
PMID- 25123116
TI - Could hyaluronic acid (HA) reduce Bacillus Calmette-Guerin (BCG) local side
effects? Results of a pilot study.
AB - BACKGROUND: Bacillus Calmette-Guerin (BCG) is considered the most effective
treatment to reduce recurrence and progression of non-muscle invasive bladder
cancer (NMIBC) but can induce local side effects leading to treatment
discontinuation or interruption. Aim of this exploratory study is to investigate
if the sequential administration of Hyaluronic acid (HA) may reduce local side
effects of BCG. METHODS: 30 consecutive subjects undergoing BCG intravesical
administration for high risk NMIBC were randomized to receive BCG only (Group A)
or BCG and HA (Group B). A 1 to 10 Visual Analog Scale (VAS) for bladder pain,
International Prostate Symptom Score (IPSS) and number of micturitions per day
were evaluated in the two groups before and after six weekly BCG instillations.
Patients were also evaluated at 3 and 6 months by means of cystostopy and urine
cytology. RESULTS: One out of 30 (3,3%) patients in group A dropped out from the
protocol, for local side effects. Mean VAS for pain was significantly lower in
group B after BCG treatment (4.2 vs. 5.8, p = 0.04). Post vs. pre treatment
differences in VAS for pain, IPSS and number of daily micturitions were all
significantly lower in group B. Three patients in group A and 4 in group B
presented with recurrent pathology at 6 month follow up. CONCLUSIONS: These
preliminary data suggest a possible role of HA in reducing BCG local side effects
and could be used to design larger randomized controlled trials, assessing safety
and efficacy of sequential BCG and HA administration. TRIAL REGISTRATION:
NCT02207608 (ClinicalTrials.gov) 01/08/2014. Policlinico Tor Vergata Ethics
Committee, resolution n 69-2011.
PMID- 25123118
TI - Admission medical records made at night time have the same quality as day and
evening time records.
AB - INTRODUCTION: A thorough and accurate admission medical record is an important
tool in ensuring patient safety during the hospital stay. Surgeons' performance
might be affected during night shifts due to sleep deprivation. The aim of the
study was to assess the quality of admission medical records during day, evening
and night time. MATERIAL AND METHODS: A total of 1,000 admission medical records
were collected from 2009 to 2013 based equally on four diagnoses: mechanical
bowel obstruction, appendicitis, gallstone disease and gastrointestinal bleeding.
The records were reviewed for errors by a pre-defined checklist based on Danish
standards for admission medical records. The time of dictation for the medical
record was registered. RESULTS: A total of 1,183 errors were found in 778
admission medical records made during day- and evening time, and 322 errors in
222 admission medical records from night time shifts. No significant overall
difference in error was found in the admission medical records when day and
evening values were compared to night values. Subgroup analyses made for all four
diagnoses showed no difference in day and evening values compared with night time
values. CONCLUSION: Night time deterioration was not seen in the quality of the
medical records.
PMID- 25123119
TI - Treatment of insufficient lactation is often not evidence-based.
AB - INTRODUCTION: Breast milk has many advantages over formula for infants in
developed and developing countries alike. Despite intentions of breastfeeding,
some women develop insufficient lactation. Treatment options traditionally
include breastfeeding education and pharmacotherapy. MATERIAL AND METHODS: An
electronic questionnaire regarding treatment of insufficient lactation was sent
to all obstetric departments (n = 21) and neonatal wards (n = 17) in Denmark.
Three main questions were included which focused on: breastfeeding education for
women, use of pharmacotherapy and availability of local guidelines. RESULTS: In
all, 30 out of a total of 38 departments participated; and among those, 93%
offered some form of breastfeeding education. 50% used either metoclopramide or
syntocinon to promote lactation. None used domperidone. 73% had a local clinical
guideline. 77% offered sessions with a lactation consultant. CONCLUSION: Despite
lack of evidence, half of the Danish obstetric departments and neonatal wards use
metoclopramide and syntocinon for insufficient lactation. Domperidone might
provide an alternative, but no departments reported its use. Management of
insufficient lactation should always be initiated by counselling and education.
Only when these treatment options are exhausted should pharmacotherapy with a
suitable medication be considered.
PMID- 25123120
TI - Improvement in health-related quality of life following Roux-en-Y gastric bypass.
AB - INTRODUCTION: This study explored whether health-related quality of life (HRQOL)
changes following Roux-en-Y gastric bypass surgery were associated with
identifiable socio-demographic or clinical characteristics, and it examined the
impact on health outcomes of changes in the Danish criteria for bariatric
surgery. MATERIAL AND METHODS: Participants (n = 55) completed the Short Form
Health Survey v2 (SF-36) before and 22 +/- 4.2 months after surgery. Information
on socio-demographics, body mass index (BMI), co-morbidity and satisfaction with
surgery were collected through patient questionnaires and hospital records.
RESULTS: There was overall improvement on all SF-36 subscales and in the mean
physical score (PCS) and mean mental score (MCS) (p = 0.001). A total of five
patients had lower PCS and 13 patients had lower MCS after surgery, but we
identified no particular characteristics associated with this poorer outcome. Co
morbidity and preoperative PCS/MCS showed a strong correlation with change in
PCS/MCS score. CONCLUSION: Gastric bypass had a positive overall effect on HRQOL,
but further investigation of individual variations is needed. We found no
significant differences in HRQOL outcome between those patients who would be
accepted for bariatric surgery under the current Danish criteria for bariatric
surgery and those patients who only fulfilled the criteria for bariatric surgery
before 2011. FUNDING: not relevant. TRIAL REGISTRATION: ClinicalTrials.gov:
NCT02032199.
PMID- 25123121
TI - Treatment of hypophosphataemic rickets in children remains a challenge.
AB - INTRODUCTION: Hypophosphataemic rickets (HR) is a rare hereditary disease
characterised by hypophosphataemia, defects in bone mineralisation and rickets.
MATERIAL AND METHODS: We searched the hospital files at H.C. Andersen Children's
Hospital, Odense University Hospital, Denmark, for children with the
International Classification of Diseases 10 codes E83.3B (vitamin D resistant
rickets) and E83.3A1 (familiar hypophosphataemia) from 1 February 2012 to 1 May
2012. Data were collected retrospectively. RESULTS: Fifteen HR children were
identified. X-linked hypophosphataemia with mutations in the phosphate-regulating
endopeptidase homologue, X-linked were present in 80%; three had autosomal
recessive HR with dentin matrix protein mutations. The children were treated with
phosphate and alphacalcidol for an average of 7.7 years +/- 5.1 standard
deviations (SD). At the latest follow-up, the mean age was 10.1 (+5.4) years, and
the mean height had declined 0.8 SD from the first contact. A total of 40% had an
actual height below -2.0 SD, and 40% underwent surgery for leg deformities. Among
the medically treated patients, five had genu varus with a mean medial femoral
condyle distance of 6.6 cm (+ 2.79), and two patients had genu valgus with a mean
medial malleolus distance of 12.3 cm (+ 1.77). Episodes of secondary
hyperparathyroidism were seen in 87%, and one patient developed transient
nephrocalcinosis. CONCLUSION: The current medical treatment for HR is
insufficient. The rarity of the disease and the treatment difficulties of HR call
for centralised management. International multi-centre trials including novel
treatment options are warranted.
PMID- 25123122
TI - Poor interpretation of chest X-rays by junior doctors.
AB - INTRODUCTION: Studies targeting medical students and junior doctors have shown
that their radiological skills are insufficient. Despite the widespread use of
chest X-ray; however, a study of Danish junior doctors' skills has not previously
been performed. MATERIAL AND METHODS: A total of 22 participants per-used a
standardised series of ten chest X-rays. The test used a multiple-choice form for
each image, and the clinical data and the tentative diagnosis of each image were
also made available to the participants. For each image, the participant chose a
single primary diagnosis; and for each diagnosis, the participant's confidence in
the diagnosis was assessed on a five-point Likert scale. The diagnoses were
divided into four groups: normal findings, chronic diseases, acute diseases and
hyperacute diseases or conditions. RESULTS: A total of 22 doctors receiving basic
clinical education (BCE) completed the study. Overall, participants correctly
established 51% of the diagnoses. The participants' overall confidence in the
primary diagnoses was 57.5% on the Likert scale, corresponding to 57.5%
confidence in the proposed diagnoses. The sensitivity was calculated to 0.49 (95%
confidence interval (CI): 0.41-0.57) and the specificity to 0.55 (95% CI: 0.41
0.68). CONCLUSION: Based on the results from this study, we conclude that BCE
doctors do not meet the minimum requirements for radiological diagnostic skills
for the use of chest X-ray that were established for this study.
PMID- 25123123
TI - Increased mortality in the elderly after emergency abdominal surgery.
AB - INTRODUCTION: The purpose of this study was to evaluate the relation between
preoperative delay and mortality in surgical patients undergoing primary
emergency laparotomy (PEL) in an unselected, well-described patient cohort in a
university hospital setting. MATERIAL AND METHODS: This study was a retrospective
analysis of patient charts and perioperative documentation in an unselected
consecutive cohort of 131 patients. Covariates for survival outcomes were
evaluated in a multivariate analysis. No external funding and no competing
interests were declared. The study was approved by The Danish Data Protection
Agency; and in pursuance of national Danish research guidelines concerning
retrospective studies, approval from ethics committee was not relevant. RESULTS:
PEL was performed in 131 patients in the observation period. The median age of
the patients was 68 years. The median time from admission to start of operation
for all patients was 9.5 hours. No association between a time to operation
exceeding six hours and post-operative mortality was found (adjusted odds ratio
(95% confidence interval) = 0.67 (0.25-1.78)). Patients over 75 years of age had
a very high mortality (47.8%). Most patients died within 30 days post
operatively. CONCLUSION: Acute admission and emergency laparotomy is associated
with a very high mortality, especially in elderly patients. However, delay in the
surgical treatment exceeding six hours is not associated with a higher mortality.
There may be a considerable potential for improving care and management in these
patients through a more systematic approach.
PMID- 25123124
TI - Single-port laparoscopic rectal surgery - a systematic review.
AB - INTRODUCTION: Single-port laparoscopic surgery (SPLS) for colonic disease has
been widely described, whereas data for SPLS rectal resection are sparse. This
review aimed to evaluate the feasibility, safety and complication profile of SPLS
for rectal diseases. METHODS: A systematic literature search of PubMed and Embase
was performed in September 2013 according to the PRISMA guidelines. Original
reports on the use of SPLS in high and low anterior resection, Hartmann's
operation and abdominoperineal resection were included. Outcome measures were
intra-operative details and complications, short-term oncological outcome and
early complication profile. RESULTS: No randomised studies or controlled clinical
studies were identified. All studies were case series or case reports. Only five
studies included more than ten patients operated with SPLS, comprising a total of
120 patients. These studies formed the basis for the final analyses of outcome.
Operative times ranged from 79 to 280 min. Conversion rates to conventional
laparoscopic surgery and to open surgery were 12% and 2.5%, respectively. The
number of harvested lymph nodes in malignant cases was 13-18. The post-operative
complication rate was 25.5%. Length of hospital stay was 1-16 days. No 30-day
mortality was reported. CONCLUSION: Short-term results suggest that SPLS for
rectal disease is feasible and safe with an acceptable complication rate when
performed by experienced surgeons in selected patients. Oncological safety and
the possible benefits remain to be proven. Future rectal SPLS procedures should
be performed in a protocolled set-up.
PMID- 25123125
TI - Metabolism and insulin signaling in common metabolic disorders and inherited
insulin resistance.
AB - Type 2 diabetes, obesity and polycystic ovary syndrome (PCOS) are common
metabolic disorders which are observed with increasing prevalences, and which are
caused by a complex interplay between genetic and environmental factors,
including increased calorie intake and physical inactivity. These metabolic
disorders are all characterized by reduced plasma adiponectin and insulin
resistance in peripheral tissues. Quantitatively skeletal muscle is the major
site of insulin resistance. Both low plasma adiponectin and insulin resistance
contribute to an increased risk of type 2 diabetes and cardiovascular disease. In
several studies, we have investigated insulin action on glucose and lipid
metabolism, and at the molecular level, insulin signaling to glucose transport
and glycogen synthesis in skeletal muscle from healthy individuals and in
obesity, PCOS and type 2 diabetes. Moreover, we have described a novel syndrome
characterized by postprandial hyperinsulinemic hypoglycemia and insulin
resistance. This syndrome is caused by a mutation in the tyrosine kinase domain
of the insulin receptor gene (INSR). We have studied individuals with this
mutation as a model of inherited insulin resistance. Type 2 diabetes, obesity and
PCOS are characterized by pronounced defects in the insulin-stimulated glucose
uptake, in particular glycogen synthesis and to a lesser extent glucose
oxidation, and the ability of insulin to suppress lipid oxidation. In inherited
insulin resistance, however, only insulin action on glucose uptake and glycogen
synthesis is impaired. This suggests that the defects in glucose and lipid
oxidation in the common metabolic disorders are secondary to other factors. In
young women with PCOS, the degree of insulin resistance was similar to that seen
in middle-aged patients with type 2 diabetes. This supports the hypothesis of an
unique pathogenesis of insulin resistance in PCOS. Insulin in physiological
concentrations stimulates glucose uptake in human skeletal muscle in vivo by
activation of the insulin signaling cascade to glucose transport through the
enzymes IRS1, PI3K, Akt2, AS160/TBC1D4 and RAC1, and to glycogen synthesis
through Akt2, inhibition of GSK3 and activation of glycogen synthase (GS) via
dephosphorylation of serine residues in both the NH2-terminal (site 2+2a) and the
COOH-terminal end (site 3a+3b). In type 2 diabetes, obesity and PCOS, there is,
although with some variation from study to study, defects in insulin signaling
through IRS1, PI3K, Akt2 and AS160/TBC1D4, which can explain reduced insulin
action on glucose transport. In type 2 diabetes an altered intracellular
distribution of SNAP23 and impaired activation of RAC1 also seem to play a role
for reduced insulin action on glucose transport. In all common metabolic
disorders, we observed an impaired insulin activation of GS, which seems to be
caused by attenuated dephosphorylation of GS at site 2+2a, whereas as the
inhibition of GSK3 and the dephosphorylation of GS at its target sites, site
3a+3a, appeared to be completely normal. In individuals with inherited insulin
resistance, we observed largely the same defects in insulin action on IRS1, PI3K,
Akt2 and GS, as well as a normal inhibition of GSK3 and dephosphorylation of GS
at site 3a+3b. In these individuals, however, a markedly reduced insulin
clearance seems to partially rescue insulin signaling to glucose transport and
GS. Adiponectin is thought to improve insulin sensitivity primarily by increasing
lipid oxidation through activation of the enzyme AMPK, and possibly via cross
talking of adiponectin with insulin signaling, and hence glucose transport and
glycogen synthesis. We demonstrated a strong correlation between plasma
adiponectin and insulin action on glucose disposal and glycogen synthesis in
obesity, type 2 diabetes and PCOS. In individuals with inherited insulin
resistance, plasma adiponectin was normal, but the correlation of adiponectin
with insulin-stimulated glucose uptake and glycogen synthesis was at least
equally strong. Moreover, we found a correlation between plasma adiponectin and
insulin activation of GS. This result is supported by a number of recent studies
of animal models and muscle cell lines, which have shown that adiponectin
augments insulin action on enzymes in the insulin signaling cascade. In contrast,
we observed no differences in the abundance or activity of AMPK in obesity, type
2 diabetes, PCOS or inherited insulin resistance. This indicates that reduced
insulin sensitivity in these conditions is not mediated via abnormal AMPK
activity. The results from these studies demonstrate that the well-established
abnormalities in insulin action on glucose uptake and glycogen synthesis are
reflected by defects in insulin signaling to these cellular processes in type 2
diabetes, obesity, and PCOS, and as expected also in inherited insulin resistance
caused by a mutation in INSR. In common metabolic disorders, low plasma
adiponectin may contribute to insulin resistance and defects in insulin
signaling, whereas in inherited insulin resistance a normal plasma adiponectin
and reduced insulin clearance could contribute to maintain a sufficient
activation of the insulin signaling cascade. The insight gained from these
studies have improved our understanding of the molecular mechanisms underlying
insulin resistance in skeletal muscle of humans, and can form the basis for
further studies, which can lead to the development of treatment that more
directly targets insulin resistance, and hence reduce the risk of type 2 diabetes
and cardiovascular disease.
PMID- 25123126
TI - Prognostic interactions between cardiovascular risk factors.
AB - BACKGROUND: Cardiovascular disease (CVD) still remains the leading cause of death
worldwide, especially in Europe where the prevalence of hypertension is 60%
higher compared with the United States and Canada and the clustering of
hypertension and the metabolic disorders central adiposity, dyslipidemia and
dysglycemia, known as the metabolic syndrome (MetS), affects 25% of the
population. Despite the great initiatives of many primary prevention strategies,
risk factor control is still poor. In an attempt to optimize risk factor control,
two issues among others have been of great debate in the past decade: (1) the
superiority of systolic blood pressure (SBP) as a risk factor in the elderly; and
(2) the clinical relevance of MetS. However, in order to further elucidate these
issues, we need to get a deeper understanding of how the cardiovascular risk
factors interact with one another. Thus, prognostic interactions were used in the
present PhD thesis to test the following hypotheses: Primary hypotheses: (1) The
superiority of SBP over diastolic blood pressure (DBP) as a risk factor occurs at
an earlier age if an individual presents with other cardiovascular risk factors.
(2) The prevalence and prognostic significance of MetS differ according to age
and gender. The first hypothesis is explored in paper 1 (for the endpoint fatal
and nonfatal (total) stroke) and paper II (for mortality from coronary heart
disease (CHD), stroke, and all-causes), while the second hypothesis is explored
in paper III (for total CHD, total stroke, and CVD mortality). METHODS: Using 34
42 cohorts from the MORGAM Project with baseline between 1982-1997, approximately
68 000-86 000 apparently healthy men and women aged 19-78 years, without CVD
(papers I-III) and not receiving antihypertensive treatment (papers I-II) were
included. During 12-13 years of follow-up, the incident events of total stroke
were up to 1957, of total CHD were 4368, and of all-cause mortality were 7903. In
papers I-II, event risk was analyzed by multivariate-adjusted Cox regressions
including SBP and DBP simultaneously, as well as other cardiovascular risk
factors and any significant interactions between variables. In paper III, MetS
prevalence and prognostic significance was considered according to modified
definitions of the International Diabetes Federation (IDF) and the revised
National Cholesterol Education Program - Adult Treatment Panel (NCEP-ATP III),
and the influence of possible interactions between age and gender on MetS
prevalence and prognostic significance was explored using logistic as well as
multivariate-adjusted Cox regressions. MetS was analyzed separately for men and
women in various age-groups. RESULTS: Taking into account the significant
interactions between cardiovascular risk factors, the results were as follows:
Papers I-II: Age-related shifts were shown for the independent relative
importance of SBP and DBP as risk factors for stroke (both total and fatal) and
all-cause mortality, but not for CHD mortality where SBP remained significant in
all ages. The prognostic shift to the superiority of SBP was significantly
established in the 6th decade, and only for stroke mortality was this shift
influenced by other cardiovascular risk factors, such that it occurred at an
earlier age in men from high-risk countries and with a higher cholesterol level.
However, from mid-age and onwards, a potential harmful effect of low DBP for the
risk of total stroke and all-cause mortality was present. Paper III: The
prevalence and prognostic significance of MetS showed great variations among
countries and were influenced by both age and gender. With older age, the
prevalence of MetS increased 5-fold in women from ages 19-39 years to 60-78 years
and 2-fold in men. The CVD risk associated with MetS was (1) higher in women than
in men especially when using the NCEP-ATP III criteria, and (2) independently of
age in men whereas in women total CHD risk decreased significantly and the total
stroke risk tended to increase (although not significant) with older age.
CONCLUSION: The present thesis elucidates through prognostic interactions the
complex interplay between cardiovascular risk factors. Our results indicate the
independent prognostic superiority of SBP in elderly Europeans, and only for
stroke mortality risk this prognostic superiority of SBP was influenced by other
cardiovascular risk factors such that it was established at an earlier age. The
prevalence and prognostic significance of MetS differed according to both age and
gender. In women, MetS was associated with higher relative event risks and the
MetS associated relative CHD risk decreased with advancing age.
PMID- 25123127
TI - Offspring body size and metabolic profile - effects of lifestyle intervention in
obese pregnant women.
AB - Worldwide, the prevalence of obesity has reached epidemic proportions. In Denmark
one third of all pregnant women are overweight and 12 % are obese. Perhaps even
more concerning, a dramatic rise in the prevalence of childhood overweight and
obesity has also been evident over recent decades. The obesity epidemic is not
simply a consequence of poor diet or sedentary lifestyles. Obesity is a
multifactorial condition in which environmental, biological and genetic factors
all play essential roles. The Developmental Origins of Health and Disease (DoHaD)
hypothesis has highlighted the link between prenatal, perinatal and early
postnatal exposure to certain environmental factors and subsequent development of
obesity and non-communicable diseases. Maternal obesity and excessive gestational
weight gain, resulting in over-nutrition of the fetus, are major contributors to
obesity and metabolic disturbances in the offspring. Pregnancy offers the
opportunity to modify the intrauterine environment, and maternal lifestyle
changes during gestation may confer health benefits to the child. The overall aim
with this PhD thesis was to study the effects of maternal obesity on offspring
body size and metabolic outcomes, with special emphasis on the effects of
lifestyle intervention during pregnancy. The thesis is based on a literature
review, description of own studies and three original papers/manuscripts (I, II
and III). In paper I, we used data from the Danish Medical Birth Registry. The
aim of this paper was to examine the impact of maternal pregestational Body Mass
Index (BMI) and smoking on neonatal abdominal circumference (AC) and weight at
birth and to define reference curves for birth AC and weight in offspring of
healthy, non-smoking, normal weight women. Data on 366,886 singletons were
extracted and analyzed using multivariate linear regressions. We found that birth
AC and weight increased with increasing pregestational BMI and decreased with
smoking. Reference curves were created for offspring of healthy, non-smoking
mothers with normal pregestational BMI. Paper II and III are based on an
offspring follow-up of a randomized controlled trial (RCT) with 360 obese
pregnant women. The intervention during pregnancy consisted of two major
components: dietary advice and physical activity. The intervention resulted in a
small, but significant difference in gestational weight gain compared to the
control group. A number of 301 completed the trial and were eligible for the
follow-up. We managed to include 157 mother and child dyads in the follow-up,
which was conducted in Odense University Hospital and Aarhus University Hospital,
Skejby between February 2010 and November 2012. At that time the children were in
the ages 2.5-3 years. In addition to the children from the RCT, a group of 97
children born to lean mothers were included as an external reference group. The
follow-up consisted of a clinical examination with anthropometric measures, DEXA
scans and fasting blood samples for evaluation of metabolic outcomes. In paper II
the effect of the maternal intervention on offspring body composition and
anthropometric outcomes was studied. The primary outcome was BMI Z-score and
secondary outcomes were: body composition values by DEXA (fat mass, lean mass and
fat percentage), BMI, percentage of overweight or obese children and skin fold
thicknesses. We found no significant differences in offspring outcomes between
randomized groups of the preceding RCT. Neither was any differences detected
between offspring of the RCT or the external reference group born to lean
mothers. Paper III focused on the metabolic outcomes in the offspring. We
additionally studied the predictive values of birth weight (BW) and birth
abdominal circumference (BAC) on metabolic risk factors. We found that both BAC
and BW were significantly associated with several risk factors in early
childhood. All metabolic measurements in RCT offspring were similar, and no
differences were detected between the RCT offspring and the external reference
group of offspring of lean mothers. Lifestyle intervention in obese pregnant
women has the potential to modify the intrauterine environment and confer long
term benefits to the child. In this follow-up study, lifestyle intervention in
pregnancy did not result in changes in offspring body composition or metabolic
risk factors at 2.8 years. This might be due to a limited difference in
gestational weight gain between follow-up attendees. When comparing offspring of
obese women with offspring of normal weight mothers all outcomes were similar. We
speculate that obese mothers entering a lifestyle intervention RCT regardless of
the intervention have a high motivation to focus on healthy lifestyle during
pregnancy, which makes it difficult to determine the effects of the randomized
lifestyle intervention compared to an unselected control group of obese women.
Our studies (paper I and III) on birth abdominal circumference show that
abdominal size at birth is a good predictor of later adverse metabolic profile.
Abdominal circumference at birth may reflect visceral adiposity and this
measurement together with birth weight are strongly associated to later adverse
metabolic outcome. Future studies should be performed in other populations to
confirm this.
PMID- 25123128
TI - Trophectoderm morphology predicts outcomes of pregnancy in vitrified-warmed
single-blastocyst transfer cycle in a Chinese population.
AB - PURPOSE: In this study, we estimated the effect of blastocoele expansion, ICM and
TE quality after warming and culture on the rates of clinical pregnancy, live
birth and miscarriage in vitrified-warmed single-blastocyst transfer cycle in a
Chinese population. METHODS: A retrospective analysis of 263 cycles of vitrified
warmed single-blastocyst transfers was performed. RESULTS: The blastocysts with
higher TE grade significantly increased the rates of clinical pregnancy (OR =
0.59, 95 % CI, 0.35-0.99, P = 0.045, grade (A + B) vs grade C) and live birth (OR
= 0.55, 95 % CI, 0.32-0.94, P = 0.029, grade (A + B) vs grade C). And the
association between TE grade and the rate of live birth didn't change after the
number of repeated cycles was adjusted (OR = 0.55, 95 % CI, 0.32-0.95, P = 0.033,
grade (A + B) vs grade C). The number of repeated cycles was a confounding factor
significantly different between the live birth and no live birth groups. By
contrast, neither blastocoele expansion nor inner cell mass was statistically
related to the rates of clinical pregnancy, live birth and miscarriage.
CONCLUSIONS: Our data firstly provided the evidence that TE grading, but not ICM
grading, was significantly associated with the clinical pregnancy rate and live
birth rate in vitrified-warmed blastocyst transfer cycles in a Chinese
population. TE morphology may help predict outcomes of pregnancy in single
blastocyst transfer.
PMID- 25123129
TI - The biomechanics of biodegradable versus titanium interference screw fixation for
anterior cruciate ligament augmentation and reconstruction.
AB - PURPOSE: The ligament augmentation and reconstruction system (LARS) is one of the
options available for anterior cruciate ligament (ACL) reconstruction. To date,
however, there are no published data regarding the biomechanical properties of
LARS fixation for ACL reconstruction. The aim of this study was to investigate
the biomechanical properties of various LARS interference-screw fixations.
METHODS: A total of 100 LARS ligaments were fixed in porcine femurs with five
different interference screws (four biodegradable screws and one titanium
interference screw) introduced from inside-out or extra-articularly outside-in.
Each group consisted of ten specimens. The constructs were cyclically stretched
and subsequently loaded until failure. We evaluated the maximum load before
failure, elongation during cyclic loading, stiffness, and failure mode. RESULTS:
Elongation during cyclical loading for all devices tested was significantly
larger between the first and 20th cycles than between the 20th and 500th cycles
(p < 0.05). Maximum failure load was not significantly lower for the
biodegradable screws than for the titanium screws (p > 0.05). All specimens
failed because of ligament pull-out from the bony tunnel. CONCLUSIONS: Our
findings suggest that biomechanical secure fixation of the LARS for ACL
reconstruction can be achieved using either biodegradable or titanium
interference screws. The stability of fixation is independent of the approach,
type of investigation, and type of fixation (extra-articular outside-in or intra
articular inside-out).
PMID- 25123130
TI - Self-management and bipolar disorder--a clinician's guide to the literature 2011
2014.
AB - This review provides clinicians and individuals with bipolar disorder (BD) with
an overview of evidence-based skills shown to be effective in BD and amenable to
self-management including psychoeducation; monitoring moods, medications, and
social function; sleep hygiene; setting goals and relapse plans; and healthy
lifestyles (physical activity, healthy eating, weight loss and management,
medical comorbidities). Currently available self-management resources for BD are
summarized by mode of delivery (workbooks, mobile technologies, internet, and
peer-led interventions). Regardless of the self-management intervention/topic,
the research suggests that personally tailored interventions of longer duration
and greater frequency may be necessary to achieve the maximal benefit among
individuals with BD. Means to support these self-management interventions as self
sustaining identities are critically needed. Hopefully, the recent investment in
patient-centered research and care will result in best practices for the self
management of BD by mode of delivery. Since self-management of BD should
complement rather than replace medical care, clinicians need to partner with
their patients to incorporate and support advances in self-management for
individuals with BD.
PMID- 25123131
TI - A combination of eicosapentaenoic acid-free fatty acid, epigallocatechin-3
gallate and proanthocyanidins has a strong effect on mTOR signaling in colorectal
cancer cells.
AB - Colorectal cancer (CRC) is one of the major causes of cancer death worldwide. The
development of novel anti-CRC agents able to overcome drug resistance and/or off
target toxicity is of pivotal importance. The mammalian target of rapamycin
(mTOR) plays a critical role in CRC, regulating protein translation and
controlling cell growth, proliferation, metabolism and survival. The aim of this
study was to explore the effect of a combination of three natural compounds,
eicosapentaenoic acid-free fatty acid (EPA-FFA), epigallocatechin-3-gallate
(EGCG) and proanthocyanidins (grape seed [GS] extract) at low cytotoxic
concentrations on CRC cells and test their activity on mTOR and translational
regulation. The CRC cell lines HCT116 and SW480 were treated for 24h with
combinations of EPA-FFA (0-150 uM), EGCG (0-175 uM) and GS extract (0-15 uM) to
evaluate the effect on cell viability. The low cytotoxic combination of EPA-FFA
150 uM, EGCG 175 uM and GS extract 15 uM completely inhibited the mTOR signaling
in HCT116 and SW480 cells, reaching an effect stronger than or comparable to that
of the mTOR inhibitor Rapamycin in HCT116 or SW480 cells, respectively. Moreover,
the treatment led to changes of protein translation of ribosomal proteins, c-Myc
and cyclin D1. In addition, we found a reduction of clonal capability in both
cell lines, with block of cell cycle in G0G1 and induction of apoptosis. Our data
suggest that the low cytotoxic combination of EPA-FFA, EGCG and GS extract,
tested for the first time here, inhibits mTOR signaling and thus could be
considered for CRC treatment.
PMID- 25123133
TI - Defective RAGE activity in embryonal rhabdomyosarcoma cells results in high PAX7
levels that sustain migration and invasiveness.
AB - Rhabdomyosarcoma is a muscle-derived malignant tumor mainly affecting children.
The most frequent variant, embryonal rhabdomyosarcoma (ERMS) is characterized by
overexpression of the transcription factor, PAX7 which prevents ERMS cells from
exiting the cell cycle and terminally differentiating. However, a role for PAX7
in the invasive properties of ERMS cells has not been investigated in detail thus
far. Here we show that ectopic expression of receptor for advanced glycation end
products (RAGE) in human ERMS cells results in the activation of a RAGE/myogenin
axis which downregulates PAX7 by transcriptional and post-translational
mechanisms, as in normal myoblasts, and reduces metastasis formation. High PAX7
sustains migration and invasiveness in ERMS cells by upregulating EPHA3 and EFNA1
and downregulating NCAM1 thus decreasing the neural cell adhesion molecule
(NCAM)/polysialylated-NCAM ratio. Microarray gene expression analysis shows that
compared with the RAGE(-ve) TE671/WT cells and similarly to primary human
myoblasts, TE671/RAGE cells show upregulation of genes involved in muscle
differentiation and cell adhesion, and downregulation of cell migration related
and major histocompatibility complex class I genes. Our data reveal a link
between PAX7 and metastasis occurrence in ERMSs, and support a role for the
RAGE/myogenin axis in metastasis suppression. Thus, low RAGE expression in ERMS
primary tumors may be predictive of metastatic behavior.
PMID- 25123132
TI - Overexpression of miR-146a in basal-like breast cancer cells confers enhanced
tumorigenic potential in association with altered p53 status.
AB - The tumor suppressor p53 is the most frequently mutated gene in human cancers,
mutated in 25-30% of breast cancers. However, mutation rates differ according to
breast cancer subtype, being more prevalent in aggressive estrogen receptor
negative tumors and basal-like and HER2-amplified subtypes. This heterogeneity
suggests that p53 may function differently across breast cancer subtypes. We used
RNAi-mediated p53 knockdown (KD) and antagomir-mediated KD of microRNAs to study
how gene expression and cellular response to p53 loss differ in luminal versus
basal-like breast cancer. As expected, p53 loss caused downregulation of
established p53 targets (e.g. p21 and miR-34 family) and increased proliferation
in both luminal and basal-like cell lines. However, some p53-dependent changes
were subtype specific, including expression of miR-134, miR-146a and miR-181b. To
study the cellular response to miR-146a upregulation in p53-impaired basal-like
lines, antagomir KD of miR-146a was performed. KD of miR-146a caused decreased
proliferation and increased apoptosis, effectively ablating the effects of p53
loss. Furthermore, we found that miR-146a upregulation decreased NF-kappaB
expression and downregulated the NF-kappaB-dependent extrinsic apoptotic pathway
(including tumor necrosis factor, FADD and TRADD) and antagomir-mediated miR-146a
KD restored expression of these components, suggesting a plausible mechanism for
miR-146a-dependent cellular responses. These findings are relevant to human basal
like tumor progression in vivo, since miR-146a is highly expressed in p53 mutant
basal-like breast cancers. These findings suggest that targeting miR-146a
expression may have value for altering the aggressiveness of p53 mutant basal
like tumors.
PMID- 25123134
TI - The effects of synthetic oligopeptide derived from enamel matrix derivative on
cell proliferation and osteoblastic differentiation of human mesenchymal stem
cells.
AB - Enamel matrix derivative (EMD) is widely used in periodontal tissue regeneration
therapy. However, because the bioactivity of EMD varies from batch to batch, and
the use of a synthetic peptide could avoid use from an animal source, a
completely synthetic peptide (SP) containing the active component of EMD would be
useful. In this study an oligopeptide synthesized derived from EMD was evaluated
for whether it contributes to periodontal tissue regeneration. We investigated
the effects of the SP on cell proliferation and osteoblast differentiation of
human mesenchymal stem cells (MSCs), which are involved in tissue regeneration.
MSCs were treated with SP (0 to 1000 ng/mL), to determine the optimal
concentration. We examined the effects of SP on cell proliferation and
osteoblastic differentiation indicators such as alkaline phosphatase activity,
the production of procollagen type 1 C-peptide and osteocalcin, and on
mineralization. Additionally, we investigated the role of extracellular signal
related kinases (ERK) in cell proliferation and osteoblastic differentiation
induced by SP. Our results suggest that SP promotes these processes in human
MSCs, and that ERK inhibitors suppress these effects. In conclusion, SP promotes
cell proliferation and osteoblastic differentiation of human MSCs, probably
through the ERK pathway.
PMID- 25123135
TI - Mammalian cytochrome P450-dependent metabolism of polychlorinated dibenzo-p
dioxins and coplanar polychlorinated biphenyls.
AB - Polychlorinated dibenzo-p-dioxins (PCDDs) and coplanar polychlorinated biphenyls
(PCBs) contribute to dioxin toxicity in humans and wildlife after bioaccumulation
through the food chain from the environment. The authors examined human and rat
cytochrome P450 (CYP)-dependent metabolism of PCDDs and PCBs. A number of human
CYP isoforms belonging to the CYP1 and CYP2 families showed remarkable activities
toward low-chlorinated PCDDs. In particular, human CYP1A1, CYP1A2, and CYP1B1
showed high activities toward monoCDDs, diCDDs, and triCDDs but no detectable
activity toward 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD). Large
amino acids located at putative substrate-recognition sites and the F-G loop in
rat CYP1A1 contributed to the successful metabolism of 2,3,7,8-tetraCDD. Rat, but
not human, CYP1A1 metabolized 3,3',4,4',5-pentachlorobiphenyl (CB126) to two
hydroxylated metabolites. These metabolites are probably less toxic than is
CB126, due to their higher solubility. Homology models of human and rat CYP1A1s
and CB126 docking studies indicated that two amino acid differences in the CB126
binding cavity were important for CB126 metabolism. In this review, the
importance of CYPs in the metabolism of dioxins and PCBs in mammals and the
species-based differences between humans and rats are described. In addition, the
authors reveal the molecular mechanism behind the binding modes of dioxins and
PCBs in the heme pocket of CYPs.
PMID- 25123136
TI - Association between phosphatase related gene variants and coronary artery
disease: case-control study and meta-analysis.
AB - Recent studies showed that the serum alkaline phosphatase is an independent
predictor of the coronary artery disease (CAD). In this work, we aimed to
summarize the association between three phosphatase related single nucleotide
polymorphisms (rs12526453, rs11066301 and rs3828329) and the risk of CAD in Han
Chinese. Our results showed that the rs3828329 of the ACP1 gene was closely
related to the risk of CAD in Han Chinese (OR = 1.45, p = 0.0006). This
significant association of rs3828329 with CAD was only found in the females
(Additive model: OR = 1.80, p = 0.001; dominant model: OR = 1.69, p = 0.03;
recessive model: OR = 1.96, p = 0.0008). Moreover, rs3828329 was likely to exert
its effect in females aged 65 years and older (OR = 2.27, p = 0.001). Further
meta-analyses showed that the rs12526453 of PHACTR11 gene (OR = 1.14, p < 0.0001,
random-effect method) and the rs11066301 of PTPN11 gene (OR = 1.15, p < 0.0001,
fixed-effects method) were associated with CAD risk in multiple populations. Our
results showed that the polymorphisms rs12526453 and rs11066301 are significantly
associated with the CAD risk in multiple populations. The rs3828329 of ACP1 gene
is also a risk factor of CAD in Han Chinese females aged 65 years and older.
PMID- 25123137
TI - Angiotensin I-converting enzyme (ACE) inhibitory activity and ACE inhibitory
peptides of salmon (Salmo salar) protein hydrolysates obtained by human and
porcine gastrointestinal enzymes.
AB - The objectives of the present study were two-fold: first, to detect whether
salmon protein fractions possess angiotensin I-converting enzyme (ACE) inhibitory
properties and whether salmon proteins can release ACE inhibitory peptides during
a sequential in vitro hydrolysis (with commercial porcine enzymes) and ex vivo
digestion (with human gastrointestinal enzymes). Secondly, to evaluate the ACE
inhibitory activity of generated hydrolysates. A two-step ex vivo and in vitro
model digestion was performed to simulate the human digestion process. Salmon
proteins were degraded more efficiently by porcine enzymes than by human
gastrointestinal juices and sarcoplasmic proteins were digested/hydrolyzed more
easily than myofibrillar proteins. The ex vivo digested myofibrillar and
sarcoplasmic duodenal samples showed IC50 values (concentration required to
decrease the ACE activity by 50%) of 1.06 and 2.16 mg/mL, respectively. The in
vitro hydrolyzed myofibrillar and sarcoplasmic samples showed IC50 values of 0.91
and 1.04 mg/mL, respectively. Based on the results of in silico studies, it was
possible to identify 9 peptides of the ex vivo hydrolysates and 7 peptides of the
in vitro hydrolysates of salmon proteins of 11 selected peptides. In both types
of salmon hydrolysates, ACE-inhibitory peptides IW, IY, TVY and VW were
identified. In the in vitro salmon protein hydrolysates an ACE-inhibitory
peptides VPW and VY were also detected, while ACE-inhibitory peptides ALPHA, IVY
and IWHHT were identified in the hydrolysates generated with ex vivo digestion.
In our studies, we documented ACE inhibitory in vitro effects of salmon protein
hydrolysates obtained by human and as well as porcine gastrointestinal enzymes.
PMID- 25123139
TI - [Official experimental testing of biomedical products. Regulatory frame and
importance of for quality, safety and efficacy].
AB - The official experimental testing of biomedicinal products provides a very
significant contribution to ensuring quality, safety and efficacy of these
indispensable medicines. Already in the prelicensing phase or to elucidate
clusters of increased adverse effects, official medicinal control laboratories
are committed to perform experimental testing. The official batch release can be
seen as external quality control of the manufacturer's release testing. For
proficient performance in these tasks, scientific research is required, in
particular on the development and refinement of test methods, and considering the
continuous development of innovative biomedicinal products. This article is aimed
at introducing the present thematic issue and in particular the regulatory basis
of experimental product testing, and illustrates by means of several examples its
great importance for the sake of the patients.
PMID- 25123138
TI - Melatonin suppresses hypoxia-induced migration of HUVECs via inhibition of
ERK/Rac1 activation.
AB - Melatonin, a naturally-occurring hormone, possesses antioxidant properties and
ameliorates vascular endothelial dysfunction. In this study, we evaluate the
impact of melatonin on the migratory capability of human umbilical vein
endothelial cells (HUVECs) to hypoxia and further investigate whether ERK/Rac1
signaling is involved in this process. Here, we found that melatonin inhibited
hypoxia-stimulated hypoxia-inducible factor-1alpha (HIF-1alpha) expression and
cell migration in a dose-dependent manner. Mechanistically, melatonin inhibited
Rac1 activation and suppressed the co-localized Rac1 and F-actin on the membrane
of HUVECs under hypoxic condition. In addition, the blockade of Rac1 activation
with ectopic expression of an inactive mutant form of Rac1-T17N suppressed HIF
1alpha expression and cell migration in response to hypoxia, as well, but
constitutive activation of Rac1 mutant Rac1-V12 restored HIF-1alpha expression,
preventing the inhibition of melatonin on cell migration. Furthermore, the anti
Rac1 effect of melatonin in HUVECs appeared to be associated with its inhibition
of ERK phosphorylation, but not that of the PI3k/Akt signaling pathway. Taken
together, our work indicates that melatonin exerts an anti-migratory effect on
hypoxic HUVECs by blocking ERK/Rac1 activation and subsequent HIF-1alpha
upregulation.
PMID- 25123140
TI - [Viral safety of biological medicinal products].
AB - Viral safety of blood donations, plasma products, viral vaccines and gene therapy
medicinal products, biotechnical-derived products and tissue and cell therapy
products is a particular challenge. These products are manufactured using a
variety of human or animal-derived starting materials and reagents; therefore,
extensive testing of donors and of cell banks established for production is
required. Furthermore, the viral safety of reagents, such as bovine sera, porcine
trypsin and human transferrin or albumin needs to be considered. Whenever
possible, manufacturing steps for inactivation or removal of viruses should be
introduced; however, sometimes it is not possible to introduce such steps for
tissues or cell-based medicinal products as the activity and viability of cells
will be compromised. It might be possible to implement steps for inactivation or
removal of potential contaminating enveloped viruses only for production of small
and stable non-enveloped viral gene vectors.
PMID- 25123141
TI - Comparing mortality among adult, general intensive care units in England with
varying intensivist cover patterns: a retrospective cohort study.
AB - INTRODUCTION: Research has demonstrated that intensivist-led care of the
critically ill is associated with reduced intensive care unit (ICU) and hospital
mortality. The objective of this study was to evaluate whether a relation exists
between intensivist cover pattern (for example, number of days of continuous
cover) and patient outcomes among adult general ICUs in England. METHODS: We
conducted a retrospective cohort study by using data from a pooled case mix and
outcome database of adult general critical care units participating in the
Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme.
Consecutive admissions to participating units for the years 2010 to 2011 were
linked to a survey of intensivist cover practices. Our primary outcome of
interest was mortality at ultimate discharge from acute-care hospital. RESULTS:
The analysis included 80,122 patients admitted to 130 ICUs in 128 hospitals.
Multivariable logistic regression analysis was used to assess the relation
between intensivist cover patterns (days of continuous cover, grade of physician
staffing at nighttime, and frequency of daily handovers) and acute hospital
mortality, adjusting for patient case mix. No relation was seen between days of
continuous cover by a single intensivist or grade of physician staffing at
nighttime and acute hospital mortality. Acute hospital mortality and ICU length
of stay were not associated with intensivist characteristics, intensivist full
time equivalents per bed, or years of clinical experience. Intensivist
participation in handover was associated with increased mortality (odds ratio,
1.27; 95% confidence interval, 1.04 to 1.55); however, only nine units reported
no intensivist participation. CONCLUSIONS: We found no relation between days of
continuous cover by a single intensivist or grade of physician staffing at
nighttime and patient outcomes in adult, general ICUs in England. Intensivist
participation in handover was associated with increased mortality; further
research to confirm or refute this finding is required.
PMID- 25123144
TI - The 2014 AHA/ACC valve disease guideline: new stages of disease, new treatment
options, and a call for earlier intervention.
PMID- 25123142
TI - Effectiveness and safety of ciclesonide in the treatment of patients with
persistent allergic or non-allergic asthma in medical practice (Data from a non
interventional study conducted in Austria).
AB - BACKGROUND: Effectiveness and safety profile of ciclesonide in the treatment of
persistent allergic or non-allergic asthma was evaluated in real-life setting in
Austria. METHODS: Prospective, single-arm, 3-month observational, non
interventional, open-label cohort study in patients with persistent asthma (with
or without allergic component) of any severity grade was conducted. Patients were
either treatment naive or switched to treatment with ciclesonide and had an
indication for treatment with inhaled corticosteroids. RESULTS: In all, 307
patients (50.8% female; mean age, 45.7 years) were prescribed ciclesonide. After
3 months of observation, the percentage of patients with daily symptoms had
declined from 33.2 to 3.9%, night-time symptoms from 21.8 to 5.2%, physical
activity limitations from 73.9 to 24.4%, and rescue medication usage from 70.0 to
45.9%. The mean total Asthma Control Questionnaire (ACQ) score was 2.32 +/- 1.14
at the first and 1.08 +/- 0.88 at the final visit. The number of patients with
well-controlled asthma (ACQ score < 1) increased considerably from 11.0% at
baseline to 52.2% at study end. Clinically important mean improvements were
observed in the total self-assessed Asthma Quality of Life score and all four
domain scores. The mean forced expiratory volume in 1 s (FEV1) increased by 0.3 L
from 2.60 +/- 0.87 L to 2.89 +/- 0.86 L, and the mean FEV1% predicted increased
from 75.1 +/- 15.4% to 83.7 +/- 14.9%. Incidence of adverse drug reactions (ADRs)
was low (4 ADRs in 3 of 307 patients, or 1.0%). CONCLUSION: This study confirmed
the effectiveness and safety of ciclesonide under routine conditions in Austria.
Improvements in symptom control, lung function, and quality of life were
observed. Ciclesonide was well tolerated.
PMID- 25123143
TI - Auditory hallucinations associated with nitrofurantoin use: case report and
review of the literature.
AB - OBJECTIVE: In this case report, we present an 83-year-old Caucasian immune
competent woman with Alzheimer's disease and organic personality disorder who
developed auditory hallucinations when treated with two nitrofurantoin (NF)
tablets (100 mg) every 12 h because of acute cystitis due to extended-spectrum
beta-lactamase-positive Escherichia coli. An 83-year-old Caucasian woman with
Alzheimer's disease developed auditory hallucinations 2 days after intake of two
NF tablets (100 mg) daily. After thorough discussion, it was decided not to
rechallenge with NF because of the serious adverse effect. After NF
discontinuation suggested by clinical pharmacist and switching to imipenem 500 mg
and cilastatin 500 mg three times daily for 7 days, symptoms significantly
improved the next day. No other drugs known to interact with NF were
administered. DISCUSSION: NF-induced adverse effects have been reported
frequently, but NF-induced auditory hallucinations with early onset in an immune
competent geriatric patient, without previous reported hallucinations or
seizures, have not been reported in the literature. Scoring according to the
Naranjo adverse drug reaction scale revealed a probable relationship between
auditory hallucinations and NF use in our patient (6 points). The exact mechanism
for the central nervous system (CNS) toxicity of NF in this patient is not known,
but we believe that the CNS penetration of NF may result in the accumulation of
toxic drug levels in CNS. CONCLUSION: This case report can be used to remind
clinicians and clinical pharmacists of keeping in mind the potential of NF
associated with auditory hallucinations, which can be easily confused with more
serious conditions.
PMID- 25123147
TI - Bronze, silver and gold: functionalized group 11 organotin sulfide clusters.
AB - The synthesis, properties and reactivity of group 11 organotin sulfide clusters
[(R(1)Sn)4(SnCl)2(MPPh3)2S8] (M = Cu, Ag), [(R(3)Sn)10Ag10S20], and
[(R(1,3)Sn)2(AuPPh3)2S4] with covalently bound, carbonyl or hydrazine-terminated
ligands R(1) = CMe2CH2C(Me)O or R(3) = CMe2CH2C(Me)NNH2 are reported.
PMID- 25123148
TI - Ultrasensitive detection of cancer cells and glycan expression profiling based on
a multivalent recognition and alkaline phosphatase-responsive electrogenerated
chemiluminescence biosensor.
AB - A multivalent recognition and alkaline phosphatase (ALP)-responsive
electrogenerated chemiluminescence (ECL) biosensor for cancer cell detection and
in situ evaluation of cell surface glycan expression was developed on a
poly(amidoamine) (PAMAM) dendrimer-conjugated, chemically reduced graphene oxide
(rGO) electrode interface. In this strategy, the multivalency and high affinity
of the cell-targeted aptamers on rGO provided a highly efficient cell recognition
platform on the electrode. The ALP and concanavalin A (Con A) coated gold
nanoparticles (Au NPs) nanoprobes allowed the ALP enzyme-catalyzed production of
phenols that inhibited the ECL reaction of Ru(bpy)3(2+) on the rGO electrode
interface, affording fast and highly sensitive ECL cytosensing and cell surface
glycan evaluation. Combining the multivalent aptamer interface and ALP
nanoprobes, the ECL cytosensor showed a detection limit of 38 CCRF-CEM cells per
mL in human serum samples, broad dynamic range and excellent selectivity. In
addition, the proposed biosensor provided a valuable insight into dynamic
profiling of the expression of different glycans on cell surfaces, based on the
carbohydrates recognized by lectins applied to the nanoprobes. This biosensor
exhibits great promise in clinical diagnosis and drug screening.
PMID- 25123149
TI - Novel tunneling system for implantation of percutaneous nerve field stimulator
electrodes: a technical note.
AB - INTRODUCTION: The field of neuromodulation continues to grow, especially in the
area of pain management. Percutaneous nerve field stimulation continues to gain
significant popularity for chronic, focal, and intractable neuropathic pain.
MATERIALS AND METHODS: Tuohy needles have been traditionally used as the
instrument of choice for subcutaneous implantation of peripheral field
stimulators. The ON-Q(r) Tunneling System (Braun Melsungen AG, Melsungen,
Germany) provides an adaptable option for subcutaneous implantation of
electrodes, with a variety of lengths and gauges available. This system uses a
disposable blunt needle and a peel-away sheath and is firm but malleable. Gentle
curves can be applied to the stylet prior to implantation. The blunt, malleable
nature of the needle and the soft Silastic sheath allow for applications in areas
with greater curvature, such as the face, and ensure a subcutaneous placement.
CONCLUSIONS: The great adaptability of this system allows for implantation of
electrodes subcutaneously with efficacy and ease. Here we present a technical
note on the use of this system for subcutaneous implantation of peripheral nerve
field stimulators.
PMID- 25123150
TI - Elevated APOBEC3B correlates with poor outcomes for estrogen-receptor-positive
breast cancers.
AB - Recent observations connected DNA cytosine deaminase APOBEC3B to the genetic
evolution of breast cancer. We addressed whether APOBEC3B is associated with
breast cancer clinical outcomes. APOBEC3B messenger RNA (mRNA) levels were
related in 1,491 primary breast cancers to disease-free (DFS), metastasis-free
(MFS), and overall survival (OS). For independent validation, APOBEC3B mRNA
expression was associated with patient outcome data in five additional cohorts
(over 3,500 breast cancer cases). In univariate Cox regression analysis,
increasing APOBEC3B expression as a continuous variable was associated with worse
DFS, MFS, and OS (hazard ratio [HR] = 1.20, 1.21, and 1.24, respectively; all P <
.001). Also, in untreated ER-positive (ER+), but not in ER-, lymph-node-negative
patients, high APOBEC3B levels were associated with a poor DFS (continuous
variable: HR = 1.29, P = .001; dichotomized at the median level, HR = 1.66, P =
.0002). This implies that APOBEC3B is a marker of pure prognosis in ER + disease.
These findings were confirmed in the analyses of five independent patient sets.
In these analyses, APOBEC3B expression dichotomized at the median level was
associated with adverse outcomes (METABRIC discovery and validation, 788 and 706
ER + cases, disease-specific survival (DSS), HR = 1.77 and HR = 1.77,
respectively, both P < .001; Affymetrix dataset, 754 ER + cases, DFS, HR = 1.57,
P = 2.46E-04; NKI295, 181 ER + cases, DFS, HR = 1.72, P = .054; and BIG 1-98,
1,219 ER + cases, breast-cancer-free interval (BCFI), HR = 1.42, P = 0.0079).
APOBEC3B is a marker of pure prognosis and poor outcomes for ER + breast cancer,
which strongly suggests that genetic aberrations induced by APOBEC3B contribute
to breast cancer progression.
PMID- 25123152
TI - Association between dental caries activity, quality of life and obesity in
Brazilian adolescents.
AB - OBJECTIVES: The impact of oral conditions on quality of life in
overweight/obesity needs to be elucidated. The aim of this study was to evaluate
the association between dental caries activity, quality of life and obesity in
Brazilian adolescents. MATERIALS AND METHODS: This study was conducted at public
schools in Brazil, on a sample of 202 adolescents, 12 years of age. For
anthropometric evaluation, the body mass index (BMI)-for-age was used. In oral
examinations, the Decayed, Missing, Filled teeth (DMFT), significant caries (SiC)
and dental caries activity (DCA) indices were used (kappa > 0.94). The Child-Oral
Impacts on Daily Performance (Child-OIDP) index was applied. The sample was
divided into two groups: O (overweight/obese; n = 101) and N (normal weight; n =
101). For data analysis, chi-square, odds ratio (OR), Wilcoxon and Pearson
correlation tests were used (P < 0.05). RESULTS: The DMFT scores were 1.67 and
2.12 and the SiC scores were 3.85 and 4.26 for groups O and N, respectively. BMI
for-age was significantly related to DCA (OR = 0.579; P < 0.000) and to SiC (OR =
0.649; P = 0.024). There were differences between the groups in eating, cleaning
mouth, emotional status, smiling, studying and the overall Child-OIDP (P < 0.05).
Positive associations between the impacts on eating, cleaning mouth and smiling
were found (P < 0.05). DMFT values showed significant correlation with the
emotional status performance in group O and the DCA was positively correlated
with performance at school in group O (P < 0.05). CONCLUSION: Obesity, dental
caries and quality of life were not correlated. Adolescents with normal weight
presented a low perception of the impact of oral conditions on quality of life;
however, it seemed to affect psychological aspects in their daily performances.
Providing adolescents with nutritional assistance may prevent obesity and dental
caries, and improve their quality of life.
PMID- 25123153
TI - The compassion deficit and what to do about it: a response to Paley.
PMID- 25123151
TI - RhoC upregulation is correlated with reduced E-cadherin in human breast cancer
specimens after chemotherapy and in human breast cancer MCF-7 cells.
AB - Therapy-resistant cancer cells are a major problem in cancer research. Recent
studies suggest that the epithelial-mesenchymal transition (EMT) is a key
mechanism in therapy resistance. Yet, the expressions of EMT markers, EMT core
regulators, and a stem cell marker of BMI1 during chemotherapy have been poorly
analyzed in clinical breast cancer specimens. In the present study, we
investigated the roles of RhoC under chemotherapy to follow up on earlier
findings demonstrating the involvement of RhoC in prostate cancer resistance to
endocrine therapy. Immunohistochemically, E-cadherin expression was significantly
lower in human breast cancer specimens analyzed after chemotherapy than specimens
biopsied before chemotherapy. Significant upregulation of fibronectin, a
mesenchymal EMT marker, was found in post-chemotherapy analysis. A study of the
EMT core regulators of SNAIL1, SNAIL2, TWIST1, and a well-known stem cell marker
of BMI1 revealed no post-chemotherapy upregulation of these molecules. In
contrast, RhoC expression was significantly upregulated in post-chemotherapy
breast cancer specimens. MCF-7 cells stably transfected with the constitutive
active (CA) RhoC plasmid manifested a reduced level of E-cadherin at the
peripheries and disorganization of actin fibers, with no accompanying
upregulation of SNAIL1, SNAIL2, TWIST1, or BMI1 in Western blots. Exposure of
etoposide on MCF-7 cells showed RhoC upregulation together with reduced
membranous expression of E-cadherin and disorganization of actin fibers. In MTT
assay, however, the CA-RhoC-expressing MCF-7 cells failed to show chemotherapy
resistance under etoposide treatment. Taken in sum, RhoC may contribute to an EMT
like process in human breast cancer during chemotherapy.
PMID- 25123155
TI - Ambulatory measurement of the ECG T-wave amplitude.
AB - Ambulatory recording of the preejection period (PEP) can be used to measure
changes in cardiac sympathetic nervous system (SNS) activity under naturalistic
conditions. Here, we test the ECG T-wave amplitude (TWA) as an alternative
measure, using 24-h ambulatory monitoring of PEP and TWA in a sample of 564
healthy adults. The TWA showed a decrease in response to mental stress and a
monotonic decrease from nighttime sleep to daytime sitting and more physically
active behaviors. Within-participant changes in TWA were correlated with changes
in the PEP across the standardized stressors (r = .42) and the unstandardized
naturalistic conditions (mean r = .35). Partialling out changes in heart rate and
vagal effects attenuated these correlations, but they remained significant.
Ambulatory TWA cannot replace PEP, but simultaneous recording of TWA and PEP
provides a more comprehensive picture of changes in cardiac SNS activity in real
life settings.
PMID- 25123154
TI - Contrasting effects of geriatric versus general medical multimorbidity on quality
of ambulatory care.
AB - OBJECTIVES: To determine whether greater burden of geriatric conditions would
have contrasting effects on quality of care (QOC) than nongeriatric, general
medical conditions. DESIGN: Cross-sectional observation over 1 year of ambulatory
care. SETTING: The Assessing Care of Vulnerable Elders-2 study. PARTICIPANTS:
Older adults prospectively screened for falls, incontinence, and dementia (N =
644). MEASUREMENTS: Participant-level QOC in absolute percentage points
calculated using 65 ambulatory care care-process quality indicators (QIs) for 13
general medical and geriatric conditions (#QIs provided/#QIs eligible). Secondary
outcomes were geriatric QOC (a subset of 38 geriatric care QIs) and medical QOC
(the 27 remaining nongeriatric QIs). Exposure variables were number of six
medical conditions (medical comorbidity) and six geriatric conditions (geriatric
comorbidity), controlling for age, sex, number of primary care visits, and site.
RESULTS: Medical and geriatric comorbidity were unrelated to each other
(correlation coefficient = 0.04, P = .27) yet had opposite effects on QOC. Each
additional medical condition was associated with a 3.2-percentage point (95%
confidence interval (CI) = 2.3-4.2 percentage point) increment in QOC, and each
additional geriatric condition was associated with 4.9-percentage point (95% CI =
3.5-6.5 percentage point) decrement in QOC. Participants with greater geriatric
comorbidity received poorer medical and geriatric QOC. CONCLUSION: Greater burden
of geriatric conditions, or geriatric multimorbidity, is associated with poorer
QOC. Geriatric multimorbidity should be targeted for better care using a
comprehensive approach.
PMID- 25123157
TI - Early angiography and clot retrieval in treatment of acute superior mesenteric
artery embolus.
PMID- 25123156
TI - Impaired fear recognition and attentional set-shifting is associated with brain
structural changes in alcoholic patients.
AB - Alcoholic patients with multiple detoxifications/relapses show cognitive and
emotional deficits. We performed structural magnetic resonance imaging and
examined performance on a cognitive flexibility task (intra-extradimensional set
shift and reversal; IED). We also presented subjects with fearful, disgust and
anger facial emotional expressions. Participants were abstaining, multiply
detoxified (MDTx; n = 12) or singly detoxified patients (SDTx; n = 17) and social
drinker controls (n = 31). Alcoholic patients were less able than controls to
change their behavior in accordance with the changing of the rules in the IED and
they were less accurate in recognizing fearful expressions in particular. They
also showed lower gray matter volume compared with controls in frontal brain
areas, including inferior frontal cortex (IFC) and insula that mediate emotional
processing, inferior parietal lobule and medial frontal cortex that mediate
attentional and motor planning processes, respectively. Impairments in
performance and some of the regional decreases in gray matter were greater in
MDTx. Gray matter volume in IFC in patients was negatively correlated with the
number of detoxifications, whereas inferior parietal lobule was negatively
correlated with the control over drinking score (impaired control over drinking
questionnaire). Performance in IED was also negatively correlated with gray
matter volume in IFC/BA47, whereas recognition of fearful faces was positively
correlated with the IFC gray matter. Repeated episodes of detoxification from
alcohol, related to severity of dependency, are coupled with altered brain
structure in areas of emotional regulation, attention and motor planning. Such
changes may confer increased inability to switch behavior according to
environmental demands and social incompetence, contributing to relapse.
PMID- 25123158
TI - Does amplitude-integrated electroencephalogram background pattern correlate with
cerebral injury in neonates with hypoxic-ischaemic encephalopathy?
AB - AIMS: To determine the correlation between amplitude-integrated
electroencephalogram (aEEG) background pattern and cerebral magnetic resonance
imaging (MRI) in infants with hypoxic-ischaemic encephalopathy (HIE) and to
examine whether the correlation changes with therapeutic hypothermia. METHODS: We
included 38 term-born infants with HIE of whom 17 were cooled. All were
continuously monitored with aEEG. Background pattern was scored at the beginning
and the end of the recording. Cerebral MRI was obtained on median day 5 (2-11
days). Abnormalities were classified using a predefined scoring system for basal
ganglia, watershed and overall injury, and then grouped into mild-moderate and
severe. RESULTS: Abnormal aEEG background pattern correlated with more severe
cerebral injury on MRI in the non-cooled infants (P < 0.01). In addition, cooled
infants had less severe cerebral injury than non-cooled infants, in particular on
T2-weighted images (watershed P = 0.04 and total injury score = 0.07).
CONCLUSIONS: Abnormal aEEG background pattern is predictive of abnormal MRI, but
therapeutic hypothermia seems to reduce this association. Thus, when cooling is
applied in a clinical setting, the predictive value of aEEG may be limited.
PMID- 25123159
TI - Immunohistochemical panel for the diagnosis of Hirschsprung's disease using
antibodies to MAP2, calretinin, GLUT1 and S100.
AB - AIMS: The diagnosis of Hirschsprung's disease is currently based on the
identification of aganglionosis and the presence of an increase in
acetylcholinesterase-positive hypertrophic nerve fibres in the large bowel
submucosa. However, acetylcholinesterase staining is laborious and requires a
skilled technician. The aim of this study was to identify a method for diagnosing
Hirschsprung's disease reliably using an immunohistochemical panel of recently
proposed markers. METHODS AND RESULTS: Sixty-nine specimens from 37 patients were
evaluated. MAP2 and calretinin antibodies were shown to stain ganglia reliably in
the submucosal and myenteric plexuses of normal tissue. By contrast, reduced
staining of ganglia was observed in patients with Hirschsprung's disease.
Staining for GLUT1 and S100 was used to evaluate the number and thickness of
nerve fibres. Gain of GLUT1 and S100 expression was in contrast to the loss of
calretinin and MAP2. Hypertrophic submucosal nerve fibres in Hirschsprung's
disease develop a perineurium with a ring-like GLUT1 staining pattern similar in
size and intensity to that observed in deeper subserosal tissue. CONCLUSIONS: The
diagnosis of Hirschsprung's disease using immunohistochemical panels could be as
accurate as with conventional frozen section techniques. In particular, the use
of a combination of markers for ganglia and hypertrophic nerve fibres
highlighting a prominent perineurium in Hirschsprung's disease could be an
alternative method.
PMID- 25123160
TI - The use of endoscopic cyclophotocoagulation for moderate to advanced glaucoma.
AB - Endoscopic Cyclophotocoagulation (ECP) is a glaucoma surgery designed to reduce
the intraocular pressure (IOP) by partially ablating the ciliary processes to
decrease aqueous humour production and secretion. The aim of this paper is to
review the literature regarding the background, indications and results of the
surgery. Although there are case reports of visually devastating complications,
including persistent hypotony and phthisis, the use of ECP is often reported in
eyes with advanced diseases. When compared with both trabeculectomy and aqueous
shunt implantation, the visual outcomes were better with ECP while the IOP
outcomes were very similar. The evidence supports ECP as a very effective
surgical option in recalcitrant glaucoma while some evidence supports its safety
for use as a primary procedure.
PMID- 25123161
TI - The stars within the melanocytic garden: unusual variants of Spitz naevi.
AB - BACKGROUND: Spitz naevi may present a wide spectrum of morphologies.
Histopathologically, many variants, including desmoplastic, angiomatoid,
verrucous/polypoid, plexiform, pagetoid, halo, myxoid, granulomatous and tubular
Spitz naevi have been described. Clinical and dermoscopic features of these
unusual variants of Spitz naevi have been reported only rarely. OBJECTIVES: The
aim of this study is to describe clinical, dermoscopic and histopathological
features of uncommon morphological variants of Spitz naevi in order to raise
awareness among clinicians about their peculiar patterns of presentation.
METHODS: We searched our image database retrospectively from 2004 to 2014 for
images of excised tumours using Spitz/Reed naevus as a keyword. RESULTS: A total
of 307 excised skin lesions with a histopathological diagnosis of Spitz/Reed
naevus were found. Among those we identified 13 uncommon variants of Spitz naevi
including six cases of desmoplastic Spitz naevus, five cases of angiomatoid Spitz
naevus and two cases of verrucous Spitz naevus. These lesions did not fulfil the
already described dermoscopic criteria of Spitz naevi, with the exception of
angiomatoid Spitz naevi, exhibiting a pinkish background and dotted vessels in
dermoscopy. Desmoplastic Spitz naevi may be difficult to differentiate from
dermatofibroma clinically, and from melanoma under dermoscopic examination.
Verrucous Spitz naevi, despite their relatively unusual clinical features, show
reassuring morphological clues histologically, which allows the differential
diagnosis from an atypical spitzoid tumour. CONCLUSIONS: In all cases an atypical
melanocytic lesion could not be excluded under dermoscopy, thus warranting
excision and histopathological examination.
PMID- 25123162
TI - Association between gestational age at birth, antenatal corticosteroids, and
outcomes at 5 years: multiple courses of antenatal corticosteroids for preterm
birth study at 5 years of age (MACS-5).
AB - BACKGROUND: The Multiple Courses of Antenatal Corticosteroids for Preterm Birth
Study (MACS) showed no benefit in the reduction of major neonatal
mortality/morbidity or neurodevelopment at 2 and 5 years of age. Using the data
from the randomized controlled trial and its follow-up, the aim of this study was
to evaluate the association between gestational ages at birth in children exposed
to single versus multiple courses of antenatal corticosteroid (ACS) therapy in
utero and outcomes at 5 years of age. METHOD: A total of 1719 children, with the
breakdown into groupings of <30, 30-36, and >= 37 weeks gestation at birth,
contributed to the primary outcome: death or survival with a disability in one of
the following domains: neuromotor, neurosensory, and neurobehavioral/emotional
disability and were included in this analysis. RESULTS: Gestational age at birth
was strongly associated with the primary outcome, p < 0.001. Overall, the
interaction between ACS groups and gestational age at birth was not significant,
p = 0.064. Specifically, in the 2 preterm categories, there was no difference in
the primary outcome between single vs. multiple ACS therapy. However, for infants
born >=37 weeks gestation, there was a statistically significant increase in the
risk of the primary outcome in multiple ACS therapy, 48/213 (22.5%) compared to
38/249 (15.3%) in the single ACS therapy; OR = 1.69 [95% CI: 1.04, 2.77]; p =
0.037. CONCLUSION: Preterm birth (<37 weeks gestation) remained the primary
factor contributing to an adverse outcome regardless of the number of courses of
ACS therapy. Children born >= 37 weeks and exposed to multiple ACS therapy may
have an increased risk of neurodevelopmental/neurosensory impairment by 5 years
of age. To optimize outcomes for infants/children, efforts in reducing the
incidence of preterm birth should remain the primary focus in perinatal research.
TRIAL REGISTRATION: This study has been registered at (identifier NCT00187382).
PMID- 25123163
TI - Itch-associated peptides: RNA-Seq and bioinformatic analysis of natriuretic
precursor peptide B and gastrin releasing peptide in dorsal root and trigeminal
ganglia, and the spinal cord.
AB - BACKGROUND: Three neuropeptides, gastrin releasing peptide (GRP), natriuritic
precursor peptide B (NPPB), and neuromedin B (NMB) have been proposed to play
roles in itch sensation. However, the tissues in which these peptides are
expressed and their positions in the itch circuit has recently become the subject
of debate. Here we used next-gen RNA-Seq to examine the expression of transcripts
coding for GRP, NPPB, NMB, and other peptides in DRG, trigeminal ganglion, and
the spinal cord as well as expression levels for their cognate receptors in these
tissues. RESULTS: RNA-Seq demonstrates that GRP is not transcribed in mouse, rat,
or human sensory ganglia. NPPB, which activates natriuretic peptide receptor 1
(NPR1), is well expressed in mouse DRG and less so in rat and human, whereas
NPPA, which also acts on the NPR1 receptor, is expressed in all three species.
Analysis of transcripts expressed in the spinal cord of mouse, rat, and human
reveals no expression of Nppb, but unambiguously detects expression of Grp and
the GRP-receptor (Grpr). The transcripts coding for NMB and tachykinin peptides
are among the most highly expressed in DRG. Bioinformatics comparisons using the
sequence of the peptides used to produce GRP-antibodies with proteome databases
revealed that the C-terminal primary sequence of NMB and Substance P can
potentially account for results from previous studies which showed GRP
immunostaining in the DRG. CONCLUSIONS: RNA-Seq corroborates a primary itch
afferent role for NPPB in mouse and potentially NPPB and NPPA in rats and humans,
but does not support GRP as a primary itch neurotransmitter in mouse, rat, or
humans. As such, our results are at odds with the initial proposal of Sun and
Chen (2007) that GRP is expressed in DRG. By contrast, our data strongly support
an itch pathway where the itch-inducing actions of GRP are exerted through its
release from spinal cord neurons.
PMID- 25123164
TI - Prognostic relevance of aberrant SOCS-1 gene promoter methylation in
myelodysplastic syndromes patients.
AB - INTRODUCTION: The inactivation of suppressor of cytokine signaling SOCS-1, a
negative regulator of cytokine pathways, by hypermethylation was shown in
hematological malignancies including Myelsplastic Syndromes. So far, its
prognostic relevance in myelodysplastic syndromes (MDS) patients has not been
understood. METHODS: Methylation status of SOCS-1 gene was analyzed in series of
100 patients using methylation-specific PCR (MS-PCR) and correlated with disease
severity, progression, and survival by comparing prognostic factors such as
hematological, clinical, and cytogenetics. RESULTS: Of the total of 100 MDS
patients analyzed, methylation of SOCS1 gene was found in 53% patients. Also, the
frequency of patients with poor and intermediate cytogenetics was observed
significantly high in methylated group (P < 0.001). Moreover, the patients with
methylated SOCS-1 gene had significantly more frequent disease progression as
compared to the patients with unmethylated SOCS-1 gene (P < 0.006). Both
progression-free survival and median overall survival were significantly shorter
in patients with methylated SOCS-1 gene when compared to the patients with
unmethylated SOCS-1 gene (P = 0.006 & P = 0.001, respectively). CONCLUSION: This
study for the first time showed that the mathylation of SOCS-1 gene plays an
important role in the disease progression and is associated with poor survival
especially among the high-risk patients. This may be due to high association
between SOCS1 methylation and higher risk subtypes of MDS (such as RAEB) in this
study.
PMID- 25123165
TI - Assessment of patients' wound-related pain experiences in University College
Hospital, Ibadan, Nigeria.
AB - This study was necessitated by the international recognition of wound-related
pain (WRP) as a must-address issue and patient-centred concerns. The aim of this
study was to assess patients' WRP experiences at rest and in relation to dressing
change. This descriptive study utilised a WRP questionnaire which incorporated a
visual analogue scale of 0-10 for data collection. A total of 109 patients
participated in this study; 95.4% of the participants experienced wound pain at
rest and during performance of activities of daily living, which were moderate
(47.1%) and severe (30.8%) in intensity. Also, 91.7% of the participants
experienced wound dressing change-related pain, mostly as moderate (47.0%) and
severe (28.0%) pain. The major factors that worsened WRP experiences were
touch/handling, change in position/movement, wound cleansing, removal of
dressings and usage of honey as a dressing agent, while the use of analgesic and
brief rest between dressing change were considered the major strategies that can
relieve WRP. WRP experiences have been reported by patients at rest, during
performance of activities of daily living and at wound dressing change. A need to
incorporate WRP assessment has been observed, which is vital in improving wound
care outcome.
PMID- 25123167
TI - FASTQSim: platform-independent data characterization and in silico read
generation for NGS datasets.
AB - BACKGROUND: High-throughput next generation sequencing technologies have enabled
rapid characterization of clinical and environmental samples. Consequently, the
largest bottleneck to actionable data has become sample processing and
bioinformatics analysis, creating a need for accurate and rapid algorithms to
process genetic data. Perfectly characterized in silico datasets are a useful
tool for evaluating the performance of such algorithms. Background contaminating
organisms are observed in sequenced mixtures of organisms. In silico samples
provide exact truth. To create the best value for evaluating algorithms, in
silico data should mimic actual sequencer data as closely as possible. RESULTS:
FASTQSim is a tool that provides the dual functionality of NGS dataset
characterization and metagenomic data generation. FASTQSim is sequencing platform
independent, and computes distributions of read length, quality scores, indel
rates, single point mutation rates, indel size, and similar statistics for any
sequencing platform. To create training or testing datasets, FASTQSim has the
ability to convert target sequences into in silico reads with specific error
profiles obtained in the characterization step. CONCLUSIONS: FASTQSim enables
users to assess the quality of NGS datasets. The tool provides information about
read length, read quality, repetitive and non-repetitive indel profiles, and
single base pair substitutions. FASTQSim allows the user to simulate individual
read datasets that can be used as standardized test scenarios for planning
sequencing projects or for benchmarking metagenomic software. In this regard, in
silico datasets generated with the FASTQsim tool hold several advantages over
natural datasets: they are sequencing platform independent, extremely well
characterized, and less expensive to generate. Such datasets are valuable in a
number of applications, including the training of assemblers for multiple
platforms, benchmarking bioinformatics algorithm performance, and creating
challenge datasets for detecting genetic engineering toolmarks, etc.
PMID- 25123166
TI - Applicable apparent diffusion coefficient of an orthotopic mouse model of gastric
cancer by improved clinical MRI diffusion weighted imaging.
AB - In vivo imaging studies in animal models are hindered by variables that
contribute to poor image quality and measurement reliability. As such we sought
to improve the diffusion coefficient (ADC) of an orthotopic mouse model of
gastric cancer in diffusion-weighted images (DWI) using alginate moulding and
Ultrasonic coupling medium. BGC-823 human gastric cancer cells were
subcutaneously injected into the abdomen of nude mice and 1 mm(3) primary tumour
was orthotopically transplanted. Alginate and coupling medium were applied to the
mice and MRI (T2 and DWI) was performed for 6 weeks. Regions of interest (ROI)
were drawn and liver and tumour ADC were evaluated. Using alginate moulding, the
mean quality total score of DW imaging was 8.53; however, in control animals this
value was 5.20 (p < 0.001). The coefficient of variation of ADC of liver in
experimental and control groups were 0.071 and 0.270 (p < 0.001), respectively,
suggesting this method may be helpful for DWI studies of important human diseases
such as gastric cancer.
PMID- 25123168
TI - Arytenoid adduction with nerve-muscle pedicle transfer vs arytenoid adduction
with and without type I thyroplasty in paralytic dysphonia.
AB - IMPORTANCE: Optimal glottal closure as well as symmetrical vocal fold masses and
tensions are essential prerequisites for normal voice production. Successful
phonosurgery depends on restoring these prerequisites to achieve long-term
improvement. OBJECTIVE: To evaluate the efficacy of the laryngeal framework
surgical treatments (arytenoid adduction with and without thyroplasty type I [AA
+/- Th-I]) compared with arytenoid adduction combined with nerve-muscle pedicle
flap transfer (AA + NMP) in unilateral vocal fold paralysis. Patterns of voice
outcome were compared over a 2-year period. DESIGN, SETTING, AND PARTICIPANTS:
Retrospective review of clinical records of 22 patients who presented to an
institutional practice with severe paralytic dysphonia between March 1999 and
December 2008, who received 2 different treatments. Postoperative follow-up was
conducted over 2 years. INTERVENTIONS: Eleven patients were treated with AA +/-
Th-I and 11 patients were treated with AA + NMP. MAIN OUTCOMES AND MEASURES:
Vocal function was evaluated preoperatively and at 3, 12, and 24 months
postoperatively. Vocal parameters evaluated were jitter, shimmer, harmonics to
noise ratio (HNR), maximum phonation time (MPT), and overall grade and
breathiness grade of the Grade-Roughness-Breathiness-Asthenia-Strain (GRBAS)
voice scale. The outcomes of voice measurements were compared within each group
across time and among the 2 groups at each time point. RESULTS: All voice
parameters showed initial postoperative improvement in both groups after 3
months. Moreover, the AA + NMP group showed significant steady improvement over
the 2-year follow-up, which did not occur in the AA +/- Th-I group. In the AA +
NMP group, MPT increased from a mean (SD) of 5.4 (2.1) s at preoperative
assessment to 21.5 (7.0) s at 24 months; jitter decreased from 8.6% (5.3%) to
1.2% (0.7%); shimmer decreased from 13.1% (6.0%) to 4.0% (1.6%); HNR increased
from 3.8 (3.3) to 9.0 (0.8); overall grade of GRBAS decreased from 2.4 (0.9) to
0.2 (0.4); and breathiness grade of GRBAS decreased from 2.0 (1.0) to 0.1 (0.3).
CONCLUSIONS AND RELEVANCE: Unlike the conventional laryngeal framework surgical
treatments, AA + NMP provided long-term voice improvement with nearly normal
voice quality. Thus, it can be considered an effective surgical treatment for
paralytic dysphonia due to unilateral vocal fold paralysis associated with large
glottal gap.
PMID- 25123169
TI - Toward modular biological models: defining analog modules based on referent
physiological mechanisms.
AB - BACKGROUND: Currently, most biomedical models exist in isolation. It is often
difficult to reuse or integrate models or their components, in part because they
are not modular. Modular components allow the modeler to think more deeply about
the role of the model and to more completely address a modeling project's
requirements. In particular, modularity facilitates component reuse and model
integration for models with different use cases, including the ability to
exchange modules during or between simulations. The heterogeneous nature of
biology and vast range of wet-lab experimental platforms call for modular models
designed to satisfy a variety of use cases. We argue that software analogs of
biological mechanisms are reasonable candidates for modularization. Biomimetic
software mechanisms comprised of physiomimetic mechanism modules offer benefits
that are unique or especially important to multi-scale, biomedical modeling and
simulation. RESULTS: We present a general, scientific method of modularizing
mechanisms into reusable software components that we call physiomimetic mechanism
modules (PMMs). PMMs utilize parametric containers that partition and expose
state information into physiologically meaningful groupings. To demonstrate, we
modularize four pharmacodynamic response mechanisms adapted from an in silico
liver (ISL). We verified the modularization process by showing that drug
clearance results from in silico experiments are identical before and after
modularization. The modularized ISL achieves validation targets drawn from
propranolol outflow profile data. In addition, an in silico hepatocyte culture
(ISHC) is created. The ISHC uses the same PMMs and required no refactoring. The
ISHC achieves validation targets drawn from propranolol intrinsic clearance data
exhibiting considerable between-lab variability. The data used as validation
targets for PMMs originate from both in vitro to in vivo experiments exhibiting
large fold differences in time scale. CONCLUSIONS: This report demonstrates the
feasibility of PMMs and their usefulness across multiple model use cases. The
pharmacodynamic response module developed here is robust to changes in model
context and flexible in its ability to achieve validation targets in the face of
considerable experimental uncertainty. Adopting the modularization methods
presented here is expected to facilitate model reuse and integration, thereby
accelerating the pace of biomedical research.
PMID- 25123170
TI - Impact of dairy consumption on essential hypertension: a clinical study.
AB - BACKGROUND: Several studies have presented evidence suggesting that dairy
consumption has beneficial effects on blood pressure (BP) in healthy subjects;
however, only a few studies have examined this possibility in patients with
established essential hypertension using ambulatory blood pressure monitoring.
The objective of this study was to investigate how consuming dairy products
impacts mean daytime systolic and diastolic BP in men and women with mild to
moderate essential hypertension. METHODS: Eighty-nine men and women with systolic
BP >= 135 mm Hg and <= 160 mm Hg and diastolic BP <= 110 mm Hg were enrolled in
this single-blind, randomized, cross-over, controlled study. Participants had to
incorporate three daily servings of dairy products or control products equivalent
in macronutrients and sodium during four-week treatment phases. Twenty-four hour
ambulatory BP and endothelial function were assessed at screening and at the end
of each dietary phase. RESULTS: The consumption of three daily servings of dairy
products led to a significant reduction in mean daytime ambulatory systolic BP (
2 mm Hg; P = 0.05) in men compared with readings after the control phase. In
women, dairy consumption had no effect on ambulatory systolic BP. Moreover,
endothelial function was significantly improved by dairy consumption in the whole
cohort. CONCLUSION: These data indicate that the consumption of three daily
servings of dairy products have beneficial effects on daytime systolic ambulatory
BP compared to a heart-healthy, dairy-free, diet in men with mild to moderate
essential hypertension. TRIAL REGISTRATION: This trial is registered at
clinicaltrials.gov as NCT01776216.
PMID- 25123171
TI - Oxidative stress and reduced responsiveness of challenged circulating leukocytes
following pulmonary instillation of metal-rich particulate matter in rats.
AB - Welding fume is an exposure that consists of a mixture of metal-rich particulate
matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests
that welders are immune compromised. Given the inability of pulmonary leukocytes
to properly respond to a secondary infection in animal models, the question arose
whether the dysfunction persisted systemically. Our aim was to evaluate the
circulating leukocyte population in terms of cellular activation, presence of
oxidative stress, and functionality after a secondary challenge, following
welding fume exposure. Rats were intratracheally instilled (ITI) with PBS or 2 mg
of welding fume collected from a stainless steel weld. Rats were sacrificed 4 and
24 h post-exposure and whole blood was collected. Whole blood was used for
cellular differential counts, RNA isolation with subsequent microarray and
Ingenuity Pathway Analysis, and secondary stimulation with LPS utilizing
TruCulture technology. In addition, mononuclear cells were isolated 24 h post
exposure to measure oxidative stress by flow cytometry and confocal microscopy.
Welding fume exposure had rapid effects on the circulating leukocyte population
as identified by relative mRNA expression changes. Instillation of welding fume
reduced inflammatory protein production of circulating leukocytes when challenged
with the secondary stimulus LPS. The effects were not related to transcription,
but were observed in conjunction with oxidative stress. These findings support
previous studies of an inadequate pulmonary immune response following a metal
rich exposure and extend those findings showing leukocyte dysfunction occurs
systemically.
PMID- 25123172
TI - Protocol for a randomized, placebo-controlled, double-blind clinical trial
investigating sacral neuromodulation for neurogenic lower urinary tract
dysfunction.
AB - BACKGROUND: Sacral neuromodulation has become a well-established and widely
accepted treatment for refractory non-neurogenic lower urinary tract dysfunction,
but its value in patients with a neurological cause is unclear. Although there is
evidence indicating that sacral neuromodulation may be effective and safe for
treating neurogenic lower urinary tract dysfunction, the number of investigated
patients is low and there is a lack of randomized controlled trials. METHODS AND
DESIGN: This study is a prospective, randomized, placebo-controlled, double-blind
multicenter trial including 4 sacral neuromodulation referral centers in
Switzerland. Patients with refractory neurogenic lower urinary tract dysfunction
are enrolled. After minimally invasive bilateral tined lead placement into the
sacral foramina S3 and/or S4, patients undergo prolonged sacral neuromodulation
testing for 3-6 weeks. In case of successful (defined as improvement of at least
50% in key bladder diary variables (i.e. number of voids and/or number of
leakages, post void residual) compared to baseline values) prolonged sacral
neuromodulation testing, the neuromodulator is implanted in the upper buttock.
After a 2 months post-implantation phase when the neuromodulator is turned ON to
optimize the effectiveness of neuromodulation using sub-sensory threshold
stimulation, the patients are randomized in a 1:1 allocation in sacral
neuromodulation ON or OFF. At the end of the 2 months double-blind sacral
neuromodulation phase, the patients have a neuro-urological re-evaluation,
unblinding takes place, and the neuromodulator is turned ON in all patients. The
primary outcome measure is success of sacral neuromodulation, secondary outcome
measures are adverse events, urodynamic parameters, questionnaires, and costs of
sacral neuromodulation. DISCUSSION: It is of utmost importance to know whether
the minimally invasive and completely reversible sacral neuromodulation would be
a valuable treatment option for patients with refractory neurogenic lower urinary
tract dysfunction. If this type of treatment is effective in the neurological
population, it would revolutionize the management of neurogenic lower urinary
tract dysfunction. TRIAL REGISTRATION: TRIAL REGISTRATION NUMBER:
http://www.clinicaltrials.gov; Identifier: NCT02165774.
PMID- 25123173
TI - Cannabinoid-mediated short-term plasticity in hippocampus.
AB - Endocannabinoids (eCBs) modulate both excitatory and inhibitory neurotransmission
in hippocampus via activation of pre-synaptic cannabinoid receptors. Here, we
present a model for cannabinoid mediated short-term depression of excitation
(DSE) based on our recently developed model for the equivalent phenomenon of
suppressing inhibition (DSI). Furthermore, we derive a simplified formulation of
the calcium-mediated endocannabinoid synthesis that underlies short-term
modulation of neurotransmission in hippocampus. The simplified model describes
cannabinoid-mediated short-term modulation of both hippocampal inhibition and
excitation and is ideally suited for large network studies. Moreover, the
implementation of the simplified DSI/DSE model provides predictions on how both
phenomena are modulated by the magnitude of the pre-synaptic cell's activity. In
addition we demonstrate the role of DSE in shaping the post-synaptic cell's
firing behaviour qualitatively and quantitatively in dependence on eCB
availability and the pre-synaptic cell's activity. Finally, we explore under
which conditions the combination of DSI and DSE can temporarily shift the fine
balance between excitation and inhibition. This highlights a mechanism by which
eCBs might act in a neuro-protective manner during high neural activity.
PMID- 25123174
TI - Magnetic resonance imaging in patients with unilateral bloody nipple discharge;
useful when conventional diagnostics are negative?
AB - BACKGROUND: Unilateral bloody nipple discharge (UBND) is mostly caused by benign
conditions such as papilloma or ductal ectasia. However, in 7-33 % of all nipple
discharge, it is caused by breast cancer. Conventional diagnostic imaging like
mammography (MMG) and ultrasonography (US) is performed to exclude malignancy.
Preliminary investigations of breast magnetic resonance imaging (MRI) assume that
it has additional value. With an increasing availability of MRI, it is of
clinical importance to evaluate this. We evaluated the additional diagnostic
value of MRI in patients with UBND in the absence of a palpable mass, with normal
conventional imaging. METHODS: All women with UBND in the period November 2007
July 2012 were included. In addition to the standard work-up (patient's history,
physical examination, MMG, and US), MRI was performed. Data from these
examinations and treatment were collected retrospectively. RESULTS: A total of
111 women (mean age 52 years; range 23-80) were included. In nine (8 %) patients,
malignancy was suspected on MRI while conventional imaging was normal. In eight
(89 %) of these patients, histology was obtained, two by core biopsy and six by
terminal duct excision. Benign conditions were found in six patients (86 %) and a
(pre-) malignant lesion in two patients. In both cases, it concerned a ductal
carcinoma in situ, which was treated with breast-conserving therapy. Moreover, in
two cases of (pre)malignancy, the MRI was interpreted as negative. CONCLUSION: In
patients with UBND who show no signs of a malignancy on conventional diagnostic
examinations, the added value of a breast MRI is limited, since a malignancy can
be demonstrated in <2 %.
PMID- 25123175
TI - Early postoperative small bowel obstruction is an independent risk factor for
subsequent adhesive small bowel obstruction in patients undergoing open
colectomy.
AB - BACKGROUND: This prospective study was performed to investigate whether
postoperative ileus (POI) or early postoperative small bowel obstruction (EPSBO)
affects the development of adhesive small bowel obstruction (SBO) in patients
undergoing colectomy. METHODS: We prospectively enrolled 1,002 patients who
underwent open colectomy by a single surgeon. POI was defined as the absence of
bowel function for more than 5 days or as a delay in oral intake beyond 7 days
postoperatively. EPSBO was defined as the clinical and radiologic identification
of SBO after resuming oral intake between postoperative days 7 and 30. Adhesive
SBO was defined as SBO developing after 30 days because of intraperitoneal
adhesion. The associations between POI, EPSBO, patient- and surgery-related
variables, and the development of adhesive SBO were analyzed. RESULTS: A total of
85 (8.5 %) patients developed POI, and 42 patients (4.2 %) developed EPSBO, with
seven patients experiencing both POI and EPSBO. During the follow-up period
(median 51 months), 70 patients (7.0 %) developed adhesive SBO, six (8.6 %) of
whom needed laparotomy. The occurrence of adhesive SBO was significantly higher
in patients with EPSBO than in those without EPSBO (26.5 vs. 7.5 % at 5 years, P
< 0.001), but not in patients with POI (13.4 vs. 7.8 % at 5 years, P = 0.158).
Multivariable analysis showed colostomy (hazard ratio [HR] 2.530, P = 0.006) and
EPSBO (HR 4.063, P < 0.001) as independent risk factors for adhesive SBO.
CONCLUSIONS: The development of adhesive SBO after colectomy is more frequent in
patients with EPSBO and colostomy; however, POI does not increase the risk of
adhesive SBO.
PMID- 25123176
TI - Clinical significance of anatomical variant of the left hepatic artery for
perihilar cholangiocarcinoma applied to right-sided hepatectomy.
AB - BACKGROUND: Full understanding of the hilar anatomy is crucial for successful
surgical resection of perihilar cholangiocarcinoma (PHC). METHODS: The three
dimensional positional relationship between the left hepatic artery (LHA) and the
umbilical portion of the left portal vein (UP) was evaluated using multidetector
row computed tomography (CT) in 58 consecutive patients who underwent right-sided
hepatectomy for Bismuth-Corlette IIIa or IV tumors. The positional relationship
of the LHA related to UP was classified into the following three types: L-UP
type, LHA runs into the left lateral section (LLS) from the left caudal side of
the UP; R-UP type, LHA runs into the LLS from the right cranial side of the UP;
and combined type, one branch of the LHA runs into the LLS from the right cranial
side of the UP, and the other from the left caudal side of the UP. RESULTS: L-UP
type LHA was observed in 53 cases (91.4 %), R-UP type in three cases (5.2 %), and
combined type in two cases (3.4 %). No cancer involvement of the LHA was seen in
any cases with L-UP type. In one case with R-UP type (one of three; 33.3 %) and
one case with combined type (one of two, 50 %), cancer invasion to the LHA was
observed at the right side of the UP, requiring combined resection of the
involved LHA. CONCLUSIONS: R-UP-type LHA running just along the left hepatic duct
may be easily involved by right-side predominant PHC when extending to the left
hepatic duct. Hepatobiliary surgeons should recognize this anatomical variant and
carefully evaluate the running courses of LHA to successfully perform R0
resection in right-sided hepatectomy for PHC.
PMID- 25123177
TI - The pathologic correlation between liver and portal vein invasion in perihilar
cholangiocarcinoma: evaluating the oncologic rationale for the American Joint
Committee on Cancer definitions of T2 and T3 tumors.
AB - BACKGROUND: The American Joint Committee on Cancer (AJCC) has recommended that
cancers with liver involvement be graded T2b and those with portal vein
involvement be graded T3, although the value of staging as prognostic factors
remains unclear. We evaluated the current definition of the T2/3 tumors for
perihilar cholangiocarcinoma. METHODS: A total of 202 patients with perihilar
cholangiocarcinoma who underwent hepatectomy without vascular resection were
enrolled. Clinicopathologic data about invasion of the liver and the unilateral
portal vein were evaluated. RESULTS: The liver and the unilateral portal vein
were involved in 100 (49.5 %) and 38 (18.8 %) patients, respectively. The
survival rates were not significantly different between patients with and without
liver invasion (48.6 vs. 52.2 %, respectively, at 5 years, P = 0.157) and between
patients with or without unilateral portal vein invasion (43.2 vs. 52.1 %,
respectively, at 5 years, P = 0.363). The survival rate of patients with tumors
staged pT2b was not significantly different from the rate of patients with pT2a
(63.4 vs. 55.6 % at 5 years, P = 0.912), and the pT2b tumor patient survival rate
was better than the rate of patients with pT3 (34.9 % at 5 years, P = 0.011).
Using multivariate analysis, nodal metastasis (P = 0.003), positive surgical
margin (P = 0.010), and Bismuth type IV tumor (P = 0.039) were identified as
independent prognostic factors. CONCLUSIONS: The liver and the unilateral portal
vein are frequently involved in perihilar cholangiocarcinoma. The determinants of
the current AJCC T2/3 tumor classifications are rational; however, subdivision of
T2 tumors may be of less clinical value.
PMID- 25123179
TI - The effect of Doppler ultrasound on early vascular interventions and clinical
outcomes after liver transplantation.
AB - BACKGROUND: During the immediate postoperative period after liver transplantation
(LT), postoperative bleeding and vascular complications (stenosis, thrombosis)
are the two most common complications that require therapeutic decisions. Doppler
ultrasound (DUS) is the established method for screening vascular patency after
LT during the immediate postoperative period. The objective of our study was to
evaluate the impact of DUS performed on postoperative days (POD) 1 and 2 on early
vascular interventions. METHODS: We studied 200 patients who had undergone living
donor or deceased donor liver transplantation between January 2011 and March
2012. Postoperative liver DUS findings of up to POD 14, including patency of
hepatic artery, portal vein, and hepatic vein, were retrieved. Patients with
normal DUS findings on POD 1 and POD 2 were classified as the normal early DUS
group. Patients with abnormal DUS findings at POD1 or POD2 were classified as the
abnormal early DUS group. Frequency of vascular interventions was compared
between the two groups. Risk factors that predict vascular interventions also
were assessed. RESULTS: On POD 1 and 2, 81.5 % (163/200) had normal DUS findings
and management was not altered by subsequent DUS findings. Two patients in the
normal group were found to have hepatic artery dissection and hepatic vein
thrombosis on routine CT on POD 7 and received vascular intervention. DUS results
in the two patients were normal until POD 6, but DUS performed after the CT on
POD 7 were consistent with the CT findings. Of the 37 recipients who showed
abnormal DUS findings on POD 1 or 2, the DUS findings were normalized or
unchanged thereafter in 33 patients and no vascular interventions were performed.
Two patients underwent hepatic artery thrombectomy on POD 2, one patient required
a portal vein thrombectomy on POD 1, and one patient died on POD 3 due to
bleeding. The overall incidence of vascular complication requiring vascular
interventions was 2.5 %. Logistic regression identified abnormal DUS findings on
POD 1 or 2 as an independent risk factor of vascular complications requiring
intervention. CONCLUSIONS: In LT recipients who demonstrate normal DUS findings
in the first 2 postoperative days, additional DUS screening may have value only
when clinically indicated.
PMID- 25123180
TI - Enhanced recovery programs in liver surgery.
PMID- 25123181
TI - Preventing inguinodynia after hernia surgery: does the type of mesh matter?
PMID- 25123182
TI - Moderate intra-abdominal free fluid on computed tomogram in patients with blunt
trauma abdomen: time to shun non-operative approach.
PMID- 25123184
TI - Epigalloccatechin-3-gallate inhibits ocular neovascularization and vascular
permeability in human retinal pigment epithelial and human retinal microvascular
endothelial cells via suppression of MMP-9 and VEGF activation.
AB - Epigalloccatechin-3-gallate (EGCG) is the main polyphenol component of green tea
(leaves of Camellia sinensis). EGCG is known for its antioxidant, anti
inflammatory, antiviral, and anti-carcinogenic properties. Here, we identify EGCG
as a new inhibitor of ocular angiogenesis and its vascular permeability. Matrix
metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play a
key role in the processes of extracellular matrix (ECM) remodeling and
microvascular permeability during angiogenesis. We investigated the inhibitory
effects of EGCG on ocular neovascularization and vascular permeability using the
retina oriented cells and animal models induced by VEGF and alkaline burn. EGCG
treatment significantly decreased mRNA and protein expression levels of MMP-9 in
the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA) and tumor necrosis
factor alpha (TNF-alpha) in human retinal pigment epithelial cells (HRPECs). EGCG
also effectively protected ARPE-19 cells from cell death and attenuated mRNA
expressions of key angiogenic factors (MMP-9, VEGF, VEGF Receptor-2) by
inhibiting generation of reactive oxygen species (ROS). EGCG significantly
inhibited proliferation, vascular permeability, and tube formation in VEGF
induced human retinal microvascular endothelial cells (HRMECs). Furthermore, EGCG
significantly reduced vascular leakage and permeability by blood-retinal barrier
breakdown in VEGF-induced animal models. In addition, EGCG effectively limited
upregulation of MMP-9 and platelet endothelial cell adhesion molecule
(PECAM/CD31) on corneal neovascularization (CNV) induced by alkaline burn. Our
data suggest that MMP-9 and VEGF are key therapeutic targets of EGCG for
treatment and prevention of ocular angiogenic diseases such as age-related
macular degeneration, diabetic retinopathy, and corneal neovascularization.
PMID- 25123186
TI - The effect of some fluoroquinolone family members on biospeciation of copper(II),
nickel(II) and zinc(II) ions in human plasma.
AB - The speciation of Cu2+, Ni2+ and Zn2+ ions in the presence of the
fluoroquinolones (FQs) moxifloxacin, ofloxacin, levofloxacin and ciprofloxacin,
in human blood plasma was studied under physiological conditions by computer
simulation. The speciation was calculated using an updated model of human blood
plasma including over 6,000 species with the aid of the program Hyss2009. The
identity and stability of metal-FQ complexes were determined by potentiometric
(310 K, 0.15 mol/L NaCl), spectrophotometric, spectrofluorimetric, ESI-MS and 1H
NMR measurements. In the case of Cu2+ ion the concentration of main low molecular
weight (LMW) plasma complex (Cu(Cis)His) is very slightly influenced by all
examined FQs. FQs show much higher influence on main plasma Ni2+ and Zn2+
complexes: (Ni(His)2 and Zn(Cys)Cit, respectively. Levofloxacin exhibits the
highest influence on the fraction of the main nickel complex, Ni(His)2, even at a
concentration level of 3*10-5 mol/L. The same effect is seen on the main zinc
complex, Zn(Cys)Cit. Calculated plasma mobilizing indexes indicate that
ciprofloxacin possesses the highest mobilizing power from plasma proteins, toward
copper ion, while levofloxacin is the most influential on nickel and zinc ions.
The results obtained indicate that the drugs studied are safe in relation to
mobilization of essential metal ions under physiological conditions. The observed
effects were explained in terms of competitive equilibrium reactions between the
FQs and the main LMW complexes of the metal ions.
PMID- 25123187
TI - Tryptophan as a probe to study the anticancer mechanism of action and specificity
of alpha-helical anticancer peptides.
AB - In the present study, a single tryptophan, as a fluorescence probe, was shifted
from the N-terminus to the middle and to the C-terminus of a 26-residue alpha
helical anticancer peptide sequence to study the mechanism of action and
specificity. The hydrophobicity of peptides, as well as peptide helicity and self
associating ability, were slightly influenced by the position change of
tryptophan in the peptide sequence, while the hemolytic activity and anticancer
activity of the peptide analogs remained the same. The tryptophan fluorescence
experiment demonstrated that peptide analogs were more selective against LUVs
mimicking cancer cell membranes than LUVs mimicking normal cell membranes. During
the interaction with target membranes, the N-terminus of an anticancer peptide
may be inserted vertically or tilted into the hydrophobic components of the
phospholipid bilayer first. The thermodynamic parameters of the peptides PNW and
PCW, when interacting with zwitterionic DMPC or negatively charged DMPS, were
determined by ITC. DSC experiments showed that peptide analogs significantly
altered the phase transition profiles of DMPC, but did not dramatically modify
the phase transition of DMPS. It is demonstrated that hydrophobic interactions
are the main driving force for peptides interacting with normal cell membranes,
whilst, electrostatic interactions dominate the interactions between peptides and
cancer cell membranes. Utilizing tryptophan as a fluorescence probe molecule
appears to be a practicable approach to determine the interaction of peptides
with phospholipid bilayers.
PMID- 25123185
TI - Effect on the aroma profile of Graciano and Tempranillo red wines of the
application of two antifungal treatments onto vines.
AB - The effect of two antifungals (boscalid+kresoxim-methyl and metrafenone) applied
onto vines under Good Agricultural Practices (GAPs) on the volatile composition
of Tempranillo and Graciano red wines was studied. Changes in aroma profile in
the wines were assessed from the combined odour activity values (OAVs) for the
volatile compounds in each of seven different odorant series (viz., ripe fruits,
fresh fruits, lactic, floral, vinous, spicy and herbaceous). Graciano wines
obtained from grapes treated with the antifungals exhibited markedly increased
concentrations of varietal volatile compounds (monoterpenes and C13
norisoprenoids) and aldehydes, and decreased concentrations of acetates and
aromatic alcohols. By contrast, the concentrations of volatile compounds in
Tempranillo wines showed different changes depending on the fungicide applied.
Also, the aroma profiles of wines obtained from treated grapes were modified,
particularly the ripe fruit nuances in Graciano wines. The OAV of this odorant
series underwent an increase by more than 60% with respect to the control wine as
a result of the increase of beta-damascenone concentration (which imparts wine a
dry plum note). The aroma profile of Tempranillo red wines containing metrafenone
residues exhibited marked changes relative to those from untreated grapes.
PMID- 25123188
TI - The toxicity mechanisms of action of Abeta25-35 in isolated rat cardiac myocytes.
AB - beta-Amyloid (Abeta) is deposited in neurons and vascular cells of the brain and
is characterized as a pathologic feature of Alzheimer's disease (AD). Recently
studies have reported that there is an association between cardiovascular risk
factors and AD, however the mechanism of this association is still uncertain. In
this study we observed Abeta had an effect on cardiovascular cells. We represent
as a major discovery that Abeta25-35 had toxicity on isolated rat cardiac
myocytes by impacting the cytoskeleton assembly and causing ER stress, ultimately
contributing to the apoptosis of the myocytes. Importantly, the activation of ER
stress and subsequent cellular dysfunction and apoptosis by Abeta25-35 was
regulated by the MAPK pathway, which could be prevented by inhibition of p38 via
pharmacological inhibitors. It was noteworthy that Abeta25-35 played a critical
role in cardiac myocytes, suggesting that Alzheimer's disease (AD) had a relation
with the heart and understanding of these associations in future will help search
for effective treatment strategies.
PMID- 25123183
TI - Imaging live cells at the nanometer-scale with single-molecule microscopy:
obstacles and achievements in experiment optimization for microbiology.
AB - Single-molecule fluorescence microscopy enables biological investigations inside
living cells to achieve millisecond- and nanometer-scale resolution. Although
single-molecule-based methods are becoming increasingly accessible to non
experts, optimizing new single-molecule experiments can be challenging, in
particular when super-resolution imaging and tracking are applied to live cells.
In this review, we summarize common obstacles to live-cell single-molecule
microscopy and describe the methods we have developed and applied to overcome
these challenges in live bacteria. We examine the choice of fluorophore and
labeling scheme, approaches to achieving single-molecule levels of fluorescence,
considerations for maintaining cell viability, and strategies for detecting
single-molecule signals in the presence of noise and sample drift. We also
discuss methods for analyzing single-molecule trajectories and the challenges
presented by the finite size of a bacterial cell and the curvature of the
bacterial membrane.
PMID- 25123189
TI - Intracellular diagnostics: hunting for the mode of action of redox-modulating
selenium compounds in selected model systems.
AB - Redox-modulating compounds derived from natural sources, such as redox active
secondary metabolites, are currently of considerable interest in the field of
chemoprevention, drug and phytoprotectant development. Unfortunately, the exact
and occasionally even selective activity of such products, and the underlying
(bio-)chemical causes thereof, are often only poorly understood. A combination of
the nematode- and yeast-based assays provides a powerful platform to investigate
a possible biological activity of a new compound and also to explore the "redox
link" which may exist between its activity on the one side and its chemistry on
the other. Here, we will demonstrate the usefulness of this platform for
screening several selenium and tellurium compounds for their activity and action.
We will also show how the nematode-based assay can be used to obtain information
on compound uptake and distribution inside a multicellular organism, whilst the
yeast-based system can be employed to explore possible intracellular mechanisms
via chemogenetic screening and intracellular diagnostics. Whilst none of these
simple and easy-to-use assays can ultimately substitute for in-depth studies in
human cells and animals, these methods nonetheless provide a first glimpse on the
possible biological activities of new compounds and offer direction for more
complicated future investigations. They may also uncover some rather unpleasant
biochemical actions of certain compounds, such as the ability of the trace
element supplement selenite to induce DNA strand breaks.
PMID- 25123190
TI - [Quality of life after operation for early Barrett's cancer: a prospective
comparison of Ivor Lewis resection versus modified Merendino resection].
PMID- 25123193
TI - I want to fly home: a terminal cancer patient's right to go home.
PMID- 25123192
TI - Changes in medication profile among patients with advanced cancer admitted to an
acute palliative care unit.
AB - PURPOSE: The decision-making process for medication use in the last weeks of life
is complex because of patient frailty and poor prognosis. Limited literature is
available on medication use in the palliative care setting, particularly in acute
palliative care units (APCUs). We examined the changes in medication profile
among hospitalized patients with advanced cancer before their palliative care
inpatient consultation team referral, after palliative care consultation, at the
time of APCU admission, and at APCU discharge or death. METHODS: We included
consecutive patients with advanced cancer who were first seen by our inpatient
palliative care consultation team and subsequently admitted to the APCU. We
retrieved data on all scheduled medications at the prespecified time points.
RESULTS: Among the 100 patients, the median duration of hospitalization was 10.5
days (interquartile range 8-15 days), and the median APCU stay was 5 days
(interquartile range 3-7 days). The average number of medications before
palliative care inpatient consultation team referral, after palliative care
consultation, at APCU admission and at APCU discharge/death was 9.2 (standard
deviation [SD] 4.5), 9.9 (SD 4.2), 10.3 (SD 3.8), and 10.1 (SD 3.8), respectively
(P = 0.03). An increasing proportion of patients received medications for symptom
control over their course of hospitalization, including systemic corticosteroids,
laxatives, neuroleptics, and antiulcer agents (P < 0.05). In contrast, the
frequency of several classes of medications such as antihypertensives,
antilipemics, and anticonvulsants decreased over time (P < 0.05). CONCLUSIONS:
Palliative care involvement was associated with an increase in symptom control
medications and decrease in medications for comorbid conditions over time.
PMID- 25123191
TI - Deep sequencing reveals clonal evolution patterns and mutation events associated
with relapse in B-cell lymphomas.
AB - BACKGROUND: Molecular mechanisms associated with frequent relapse of diffuse
large B-cell lymphoma (DLBCL) are poorly defined. It is especially unclear how
primary tumor clonal heterogeneity contributes to relapse. Here, we explore
unique features of B-cell lymphomas - VDJ recombination and somatic hypermutation
- to address this question. RESULTS: We performed high-throughput sequencing of
rearranged VDJ junctions in 14 pairs of matched diagnosis-relapse tumors, among
which 7 pairs were further characterized by exome sequencing. We identify two
distinctive modes of clonal evolution of DLBCL relapse: an early-divergent mode
in which clonally related diagnosis and relapse tumors diverged early and
developed in parallel; and a late-divergent mode in which relapse tumors
developed directly from diagnosis tumors with minor divergence. By examining
mutation patterns in the context of phylogenetic information provided by VDJ
junctions, we identified mutations in epigenetic modifiers such as KMT2D as
potential early driving events in lymphomagenesis and immune escape alterations
as relapse-associated events. CONCLUSIONS: Altogether, our study for the first
time provides important evidence that DLBCL relapse may result from multiple,
distinct tumor evolutionary mechanisms, providing rationale for therapies for
each mechanism. Moreover, this study highlights the urgent need to understand the
driving roles of epigenetic modifier mutations in lymphomagenesis, and immune
surveillance factor genetic lesions in relapse.
PMID- 25123194
TI - Unanticipated frequency and consequences of regimen-related diarrhea in patients
being treated with radiation or chemoradiation regimens for cancers of the head
and neck or lung.
AB - PURPOSE: To better understand the indirect effects of standard courses of
radiation therapy (RT) on distant tissue toxicity, we evaluated the frequency,
course, and health and economic burden of regimen-related diarrhea in a large,
multinational group of patients who were being treated for cancers of the head
and neck (HNC) or lung (NSCLC). METHODS: In this exploratory, prospective study,
284 patients being treated for HNC and 60 being treated for NSCLC were stratified
into four cohorts to evaluate the effect of radiation alone and radiation plus
concomitant chemotherapy (CRT) on radiation-induced diarrhea (RID). RID was
assessed daily throughout RT using a patient-reported five-point categorical
scale. Health and resource use outcomes were evaluated at least weekly during
radiation. RESULTS: Moderate to severe RID was reported in all groups and was
worse among patient being treated with concomitant chemoradiation (CRT). Whereas
29 % of patients treated with radiation only developed RID, the incidence was 42
% among CRT-treated patients. Tumor site did not impact the rate of RID, but did
impact the rate of development and was more acute in patients being treated for
NSCLC than for HNC. Patients with significant RID had worse health and resource
use outcomes than did patients without RID regardless of the form of treatment. G
tube placement, weight loss, unplanned office visits, and in-patient days were
adversely affected by RID. Not surprisingly, patients treated with CRT had poorer
health and resource outcomes than RT only patients, even in the absence of RID.
CONCLUSION: In addition to local tissue toxicities, our results suggest that
focal radiation may also be associated with significant distant tissue-centric
injury here represented by RID. While these changes were seen with radiation
alone, the addition of chemotherapy increased the incidence and burden of
illness. RID adversely impacted resource use. This unanticipated finding supports
the hypothesis that focal radiation therapy results in pathobiological changes
that extend beyond the radiation field and which can produce distant changes.
PMID- 25123195
TI - Ligand-size dependent water proton relaxivities in ultrasmall gadolinium oxide
nanoparticles and in vivo T1 MR images in a 1.5 T MR field.
AB - The dependence of longitudinal (r1) and transverse (r2) water proton relaxivities
of ultrasmall gadolinium oxide (Gd2O3) nanoparticles on the surface coating
ligand-size was investigated. Both r1 and r2 values decreased with increasing
ligand-size. We attributed this to the ligand-size effect. In addition the
effectiveness of d-glucuronic acid-coated ultrasmall Gd2O3 nanoparticles as T1
magnetic resonance imaging (MRI) contrast agents was confirmed by measuring the
in vitro cytotoxicity and using in vivo T1 MR images in a mouse in a 1.5 T MR
field.
PMID- 25123196
TI - Caffeine consumption around an exercise bout: effects on energy expenditure,
energy intake, and exercise enjoyment.
AB - Combining an exercise and nutritional intervention is arguably the optimal method
of creating energy imbalance for weight loss. This study sought to determine
whether combining exercise and caffeine supplementation was more effective for
promoting acute energy deficits and manipulations to substrate metabolism than
exercise alone. Fourteen recreationally active participants (mean +/- SD body
mass index: 22.7 +/- 2.6 kg/m2) completed a resting control trial (CON), a
placebo exercise trial (EX), and a caffeine exercise trial (EX+CAF, 2 * 3 mg/kg
of caffeine 90 min before and 30 min after exercise) in a randomized, double
blinded design. Trials were 4 h in duration with 1 h of rest, 1 h of cycling at
~65% power at maximum O2 consumption or rest, and a 2-h recovery. Gas exchange,
appetite perceptions, and blood samples were obtained periodically. Two hours
after exercise, participants were offered an ad libitum test meal where energy
and macronutrient intake were recorded. EX+CAF resulted in significantly greater
energy expenditure and fat oxidation compared with EX (+250 kJ; +10.4 g) and CON
(+3,126 kJ; +29.7 g) (P < 0.05). A trend for reduced energy and fat intake
compared with CON (-718 kJ; -8 g) (P = 0.055) was observed. Consequently, EX+CAF
created a greater energy deficit (P < 0.05). Caffeine also led to exercise being
perceived as less difficult and more enjoyable (P < 0.05). Combining caffeine
with exercise creates a greater acute energy deficit, and the implications of
this protocol for weight loss or maintenance over longer periods of time in
overweight/obese populations should be further investigated.
PMID- 25123197
TI - Hemodynamic responses during graded and constant-load plantar flexion exercise in
middle-aged men and women with type 2 diabetes.
AB - We tested the hypotheses that type 2 diabetes (T2D) impairs the 1) leg
hemodynamic responses to an incremental intermittent plantar-flexion exercise and
2) dynamic responses of leg vascular conductance (LVC) during low-intensity (30%
maximal voluntary contraction, MVC) and high-intensity (70% MVC) constant-load
plantar-flexion exercise in the supine posture. Forty-four middle-aged
individuals with T2D (14 women), and 35 healthy nondiabetic (ND) individuals (18
women) were tested. Leg blood flow (LBF) was measured between each contraction
using venous occlusion plethysmography. During the incremental test peak force
(Fpeak) relative to MVC was significantly reduced (P < 0.05) in men and women
with T2D compared with their respective nondiabetic counterparts. Peak LBF and
the slope of LBF relative to percentage Fpeak were also reduced (P < 0.05) in
women with T2D compared with healthy women (peak blood flow, 460.6 +/- 126.8 vs.
628.3 +/- 347.7 ml/min; slope, 3.78 +/- 1.74 vs. 5.85 +/- 3.14 ml.min(-1).%Fpeak
(-1)) and in men with T2D compared with nondiabetic men (peak blood flow, 621.7
+/- 241.3 vs. 721.2 +/- 359.7 ml/min; slope, 5.75 +/- 2.66 vs. 6.33 +/- 3.63
ml.min(-1).%Fpeak (-1)). During constant-load contractions at 30% MVC T2D did not
affect the dynamic responses of LVC (LBF/MAP). However, at 70% MVC [completed by
a subgroup of participants (20 with T2D, 6 women; 13 ND, 6 women)] the time
constant of the second growth phase of LVC was longer and the amplitude of the
first growth phase was lower (P < 0.05 for both) in men and women with T2D. The
results suggest that the T2D-induced impairments in performance of the leg
muscles are related to reductions in blood flow in both men and women.
PMID- 25123198
TI - Acute effects of taurine on sarcoplasmic reticulum Ca2+ accumulation and
contractility in human type I and type II skeletal muscle fibers.
AB - Taurine occurs in high concentrations in muscle and is implicated in numerous
physiological processes, yet its effects on many aspects of contractility remain
unclear. Using mechanically skinned segments of human vastus lateralis muscle
fibers, we characterized the effects of taurine on sarcoplasmic reticulum (SR)
Ca2+ accumulation and contractile apparatus properties in type I and type II
fibers. Prolonged myoplasmic exposure (>10 min) to taurine substantially
increased the rate of accumulation of Ca2+ by the SR in both fiber types, with no
change in the maximum amount accumulated; no such effect was found with
carnosine. SR Ca2+ accumulation was similar with 10 or 20 mM taurine, but was
significantly slower at 5 mM taurine. Cytoplasmic taurine (20 mM) had no
detectable effects on the responsiveness of the Ca2+ release channels in either
fiber type. Taurine caused a small increase in Ca2+ sensitivity of the
contractile apparatus in type I fibers, but type II fibers were unaffected;
maximum Ca(2+)-activated force was unchanged in both cases. The effects of
taurine on SR Ca2+ accumulation (1) only became apparent after prolonged
cytoplasmic exposure, and (2) persisted for some minutes after complete removal
of taurine from the cytoplasm, consistent with the hypothesis that the effects
were due to an action of taurine from inside the SR. In summary, taurine
potentiates the rate of SR Ca2+ uptake in both type I and type II human fibers,
possibly via an action from within the SR lumen, with the degree of potentiation
being significantly reduced at low physiological taurine levels.
PMID- 25123199
TI - Quantitative and temporal differential recovery of articular and muscular
limitations of knee joint contractures; results in a rat model.
AB - Joint contractures alter the mechanical properties of articular and muscular
structures. Reversibility of a contracture depends on the restoration of the
elasticity of both structures. We determined the differential contribution of
articular and muscular structures to knee flexion contractures during spontaneous
recovery. Rats (250, divided into 24 groups) had one knee joint surgically fixed
in flexion for six different durations, from 1 to 32 wk, creating joint
contractures of various severities. After the fixation was removed, the animals
were left to spontaneously recover for 1 to 48 wk. After the recovery periods,
animals were killed and the knee extension was measured before and after division
of the transarticular posterior muscles using a motorized arthrometer. No
articular limitation had developed in contracture of recent onset (<=2 wk of
fixation, P > 0.05); muscular limitations were responsible for the majority of
the contracture (34 +/- 8 degrees and 38 +/- 6 degrees , respectively; both P <
0.05). Recovery for 1 and 8 wk reversed the muscular limitation of contractures
of recent onset (1 and 2 wk of fixation, respectively). Long-lasting contractures
(>=4 wk of fixation) presented articular limitations, irreversible in all 12
durations of recovery compared with controls (all 12 P < 0.05). Knee flexion
contractures of recent onset were primarily due to muscular structures, and they
were reversible during spontaneous recovery. Long-lasting contractures were
primarily due to articular structures and were irreversible. Comprehensive
temporal and quantitative data on the differential reversibility of mechanically
significant alterations in articular and muscular structures represent novel
evidence on which to base clinical practice.
PMID- 25123200
TI - Cardiovascular and thermoregulatory biomarkers of heat stroke severity in a
conscious rat model.
AB - Multiorgan failure is a catastrophic consequence of heat stroke (HS) and
considered the underlying etiology of mortality. Identifying novel biomarkers
capable of predicting the extent of HS-induced organ damage will enhance point-of
care triage and treatment. Conscious male F344 rats (n = 32) were
radiotelemetered for continuous core temperature (Tc), heart rate, and arterial
pressure measurement. Twenty-two animals were exposed to ambient temperature of
37 degrees C to a maximum Tc of 41.9 +/- 0.1 degrees C. Rats were euthanized at
24 h of recovery for analysis of plasma biomarkers [cardiac troponin I (cTnI),
blood urea nitrogen (BUN), alanine aminotransferase (ALT), albumin, glucose] and
histology. Tc profiles observed during recovery stratified HS severity into Mild,
Moderate, and Severe. Eleven (50%) animals exhibited an acute compensatory
hemodynamic response to heat exposure and a monophasic Tc profile consisting of
sustained hyperthermia (~1 degrees C). Five (23%) rats displayed hemodynamic
challenge and a biphasic Tc profile with rapid return to baseline followed by
rebound hyperthermia. All biomarkers were significantly altered from control
values (P < 0.05). Four (18%) animals exhibited significant hemodynamic
compromise during heat and a triphasic profile characterized by rapid cooling to
baseline Tc, rebound hyperthermia, and subsequent hypothermia (~35 degrees C)
through 24 h. cTnI showed a 40-fold increase over CON (P < 0.001) and correlated
with BUN (r = 0.912) consistent with cardiorenal failure. Hypoglycemia correlated
with ALT (r = 0.824) suggestive of liver dysfunction. Histology demonstrated
myocardial infarction, renal tubular necrosis, and acute liver necrosis. Two (9%)
animals succumbed during HS recovery. This study identified novel biomarkers that
predict HS severity and organ damage during acute recovery that could provide
clinical significance for identifying key biomarkers of HS pathogenesis.
PMID- 25123202
TI - Copper metal-organic framework nanocrystal for plane effect nonenzymatic electro
catalytic activity of glucose.
AB - This work describes the first demonstration of nanocrystal plane dependent
nonenzymatic electro-catalytic glucose activity of [Cu3(btc)2] nanocrystals with
different shapes (nanocube, truncated cube, cuboctahedron, and octahedron). From
electrochemical results, the obtained [Cu3(btc)2] nanocube modified electrode
shows the best nonenzymatic electro-catalytic glucose activity. Interestingly,
decreasing the {100} crystal planes from cubes to octahedra, changes the
nonenzymatic electro-catalytic activity from highly sensitive to general.
PMID- 25123201
TI - Protective effect of sex on chronic stress- and depressive behavior-induced
vascular dysfunction in BALB/cJ mice.
AB - The presence of chronic, unresolvable stresses leads to negative health outcomes,
including development of clinical depression/depressive disorders, with outcome
severity being correlated with depressive symptom severity. One of the major
outcomes associated with chronic stress and depression is the development of
cardiovascular disease (CVD) and an elevated CVD risk profile. However, in
epidemiological research, sex disparities are evident, with premenopausal women
suffering from depressive symptoms more acutely than men, but also demonstrating
a relative protection from the onset of CVD. Given this, we investigated the
differential effect of sex on conduit artery and resistance arteriolar function
in male and female mice following 8 wk of an unpredictable chronic mild stress
(UCMS) protocol. In males, plasma cortisol and depressive symptom severity (e.g.,
coat status, anhedonia, delayed grooming) were elevated by UCMS. Endothelium
dependent dilation to methacholine/acetylcholine was impaired in conduit arteries
and skeletal muscle arterioles, suggesting a severe loss of nitric oxide
bioavailability and increased production of thromboxane A2 vs. prostaglandin I2
associated with elevated reactive oxygen species (ROS) and an increased level of
systemic inflammation. Endothelium-independent dilation was intact. In females,
depressive symptoms and plasma cortisol increases were more severe than in males,
although alterations to vascular reactivity were blunted, including the effects
of elevated ROS and inflammation on dilator responses. These results suggest that
compared with males, female rats are more susceptible to chronic stress in terms
of the severity of depressive behaviors, but that the subsequent development of
vasculopathy is blunted owing to an improved ability to tolerate elevated ROS and
systemic inflammatory stress.
PMID- 25123203
TI - Acute kidney injury after snakebite accident treated in a Brazilian tertiary care
centre.
AB - AIM: Acute kidney injury (AKI) is one of the main causes of morbidity and
mortality in cases of envenomation by venomous snakes. The present study was
carried out to investigate the clinical and laboratory manifestations in
accidents with venomous snakes and the risk factors associated with AKI in these
accidents. METHODS: A retrospective study was carried out with patients victims
of snakebite admitted to a reference centre. AKI was defined according to the
RIFLE and AKIN criteria. RESULTS: A total of 276 patients were included, of which
230 (83.7%) were males. AKI was observed in 42 cases (15.2%). The mean genus
involved in the accidents was Bothrops (82.2%). Mean age of patients with AKI was
higher than in patients without AKI (43 +/- 20 vs. 34 +/- 21 years, P = 0.015).
The time elapsed between the accident and medical care was higher in the AKI
group (25 +/- 28 vs. 14 +/- 16h, P = 0.034), as well as the time elapsed between
the accident and the administration of antivenom (30.7 +/- 27 vs. 15 +/- 16 h, P
= 0.01). Haemodialysis was required in 30% of cases and complete renal function
recovery was observed in 54.8% of cases at hospital discharge. There were four
deaths, none of which had AKI. Factors associated with AKI were haemorrhagic
abnormalities (P = 0.036, OR = 6.718, 95% CI: 1.067-25.661) and longer length of
hospital stay (P = 0.004, OR = 1.69, 95% CI 1.165-2.088). CONCLUSION: Acute
kidney injury is an important complication of snakebite accidents, showing low
mortality, but high morbidity, which can lead to partial renal function recovery.
PMID- 25123204
TI - Protocol for the induction of subarachnoid hemorrhage in mice by perforation of
the Circle of Willis with an endovascular filament.
AB - Genetically engineered mice are a valuable tool to investigate the molecular and
cellular mechanisms leading to brain damage following subarachnoid hemorrhage
(SAH). Therefore, several murine SAH models were developed during the last 15
years. Among those models, the perforation of the Circle of Willis by an
endovascular filament or "filament model" turned out to become the most popular
one, since it is believed to reproduce some of the most prominent
pathophysiological features observed after human SAH. Despite the importance of
the endovascular filament model for SAH research, relatively few studies were
published using this technique during the past years and a number of laboratories
reported problems establishing the technique. This triggered discussions about
the standardization, reproducibility, and the reliability of the model. In order
to improve this situation, the current paper aims to provide a comprehensive
hands-on protocol of the murine endovascular filament model. The protocol proved
to result in induction of SAH in mice with high intrapersonal and interpersonal
reproducibility and is based on our experience with this technique for more than
10 years. By sharing our experience with this valuable model, we aim to initiate
a constantly ongoing discussion process on the improvement of standards and
techniques in the field of experimental SAH research.
PMID- 25123206
TI - Commentary: predictors of severe outcomes associated with Clostridium difficile
infection in inflammatory bowel disease patients.
PMID- 25123205
TI - Effects of childhood abuse on adult obesity: a systematic review and meta
analysis.
AB - Controversy exists surrounding the role of childhood abuse in obesity
development. This is a meta-analysis of observational studies on the role of
childhood abuse in adult obesity. Systematic searches of PubMed, PsycInfo,
Medline and CINAHL resulted in 23 cohort studies (4 prospective, 19
retrospective) with n=112,708 participants, containing four abuse types
(physical, emotional, sexual, general). Four studies reported dose-response
effects. A random effects model was used to quantify effect sizes, meta
regression/subgroup analysis for identifying potential moderating variables and
Egger's test for publication bias. Adults who reported childhood abuse were
significantly more likely to be obese (odds ratio [OR]: 1.34, 95% confidence
interval [CI]: 1.24-1.45, P<0.001). All four types of abuse were significantly
associated with adult obesity: physical (OR: 1.28, 95% CI: 1.13-1.46), emotional
(OR: 1.36, 95% CI: 1.08-1.71), sexual (OR: 1.31, 95% CI: 1.13-1.53) and general
abuse (OR: 1.45, 95% CI: 1.25-1.69). Severe abuse (OR: 1.50, 95% CI: 1.27-1.77)
was significantly more associated with adult obesity (P=0.043) compared with
light/moderate abuse (OR: 1.13, 95% CI: 0.91-1.41). We found no significant
effects of study design (prospective vs. retrospective, P=0.07), age (P=0.96) or
gender (P=0.92). Publication bias was evident (Egger's test P=0.007), but effect
sizes remained statistically significant in sensitivity analyses. Childhood abuse
was clearly associated with being obese as an adult, including a positive dose
response association. This suggests that adverse life experiences during
childhood plays a major role in obesity development, potentially by inducing
mental and emotional perturbations, maladaptive coping responses, stress,
inflammation and metabolic disturbances.
PMID- 25123207
TI - Production and supply of high-quality food protein for human consumption:
sustainability, challenges, and innovations.
AB - The Food and Agriculture Organization of the United Nations estimates that 843
million people worldwide are hungry and a greater number suffer from nutrient
deficiencies. Approximately one billion people have inadequate protein intake.
The challenge of preventing hunger and malnutrition will become even greater as
the global population grows from the current 7.2 billion people to 9.6 billion by
2050. With increases in income, population, and demand for more nutrient-dense
foods, global meat production is projected to increase by 206 million tons per
year during the next 35 years. These changes in population and dietary practices
have led to a tremendous rise in the demand for food protein, especially animal
source protein. Consuming the required amounts of protein is fundamental to human
growth and health. Protein needs can be met through intakes of animal and plant
source foods. Increased consumption of food proteins is associated with increased
greenhouse gas emissions and overutilization of water. Consequently, concerns
exist regarding impacts of agricultural production, processing and distribution
of food protein on the environment, ecosystem, and sustainability. To address
these challenging issues, the New York Academy of Sciences organized the
conference "Frontiers in Agricultural Sustainability: Studying the Protein Supply
Chain to Improve Dietary Quality" to explore sustainable innovations in food
science and programming aimed at producing the required quality and quantity of
protein through improved supply chains worldwide. This report provides an
extensive discussion of these issues and summaries of the presentations from the
conference.
PMID- 25123208
TI - Clinical and economic outcomes of nutrition interventions across the continuum of
care.
AB - Optimal nutrition across the continuum of care plays a key role in the short- and
long-term clinical and economic outcomes of patients. Worldwide, an estimated one
quarter to one-half of patients admitted to hospitals each year are malnourished.
Malnutrition can increase healthcare costs by delaying patient recovery and
rehabilitation and increasing the risk of medical complications. Nutrition
interventions have the potential to provide cost-effective preventive care and
treatment measures. However, limited data exist on the economics and impact
evaluations of these interventions. In this report, nutrition and health system
researchers, clinicians, economists, and policymakers discuss emerging global
research on nutrition health economics, the role of nutrition interventions
across the continuum of care, and how nutrition can affect healthcare costs in
the context of hospital malnutrition.
PMID- 25123209
TI - Antibody-drug conjugates: an emerging modality for the treatment of cancer.
AB - Antibody-drug conjugates (ADCs) offer promise as a therapeutic modality that can
potentially reduce the toxicities and poor therapeutic indices caused by the lack
of specificity of conventional anticancer therapies. ADCs combine the potency of
cytotoxic agents with the target selectivity of antibodies by chemically linking
a cytotoxic payload to an antibody, potentially creating a synthetic molecule
that will deliver targeted antitumor therapy that is both safe and efficacious.
The ADC repertoire contains a range of payload molecules, antibodies, and
linkers. Two ADC molecules, Kadcyla(r) and Adcetris(r), have been approved by the
FDA, and many more are currently in clinical development.
PMID- 25123211
TI - Architecture and morphology of the human ventromedial prefrontal cortex.
AB - A previous report identified the location of comparable architectonic areas in
the ventral frontal cortex of the human and macaque brains [S. Mackey & M.
Petrides (2010) Eur. J. Neurosci., 32, 1940-1950]. The present article provides
greater detail with regard to the definition of architectonic areas within the
ventromedial part of the human ventral frontal cortex and describes their
location: (i) in Montreal Neurological Institute proportional stereotactic space;
and (ii) in relation to sulcal landmarks. Structural magnetic resonance scans of
four brains were obtained before the preparation of the histological specimens,
so that the architectonic parcellation could be reconstructed in its original
three-dimensional volume. The areal density of individual cortical layers was
sampled quantitatively in the ventromedial prefrontal cortex of eight brains (16
hemispheres). The agranular cortex along the ventral edge of the corpus callosum
and posterior margin of the ventromedial surface is replaced by a graded series
of increasingly granular and more complexly laminated areas that succeed one
another in a posterior-to-anterior direction. In parallel, the width of the
supragranular layers (i.e. layers II and III) increases as compared with the
infragranular layers (i.e. layers V and VI) from posterior to anterior. A measure
of how rapidly cortical features change at areal boundaries also showed that the
rate of change in the granule and pyramidal cell densities of layers IV and V,
respectively, was greater at the borders between posterior areas than between
anterior areas. This article will facilitate the anatomical identification and
comparison of experimental data involving the human vmPFC.
PMID- 25123210
TI - Long-term systemic inflammation and cognitive impairment in a population-based
cohort.
AB - OBJECTIVES: Evidence suggests inflammation is associated with cognitive
impairment, but previous epidemiological studies have reported conflicting
results. DESIGN: Prospective population-based cohort. SETTING: Epidemiology of
Hearing Loss Study participants. PARTICIPANTS: Individuals without cognitive
impairment in 1998-2000 (N = 2,422; 1,947 with necessary data). MEASUREMENTS:
Cognitive impairment (Mini-Mental State Examination score <24 or diagnosis of
dementia) was ascertained in 1998-2000, 2003-2005, and 2009-2010. Serum C
reactive protein (CRP) and interleukin-6 (IL-6) were measured in 1988-1990, 1998
2000, and 2009-2010; tumor necrosis factor-alpha was measured from 1998-2000.
RESULTS: Participants with high CRP in 1988-1990 and 1998-2000 had lower risk of
cognitive impairment than those with low CRP at both time points (hazard ratio
(HR) = 0.46, 95% confidence interval (CI) = 0.26-0.80). Risk did not differ
according to 10-year IL-6 profile or baseline inflammation category in the whole
cohort. In sensitivity analyses restricted to statin nonusers, those with high IL
6 at both times had greater risk of cognitive impairment than those with low IL-6
at both times (HR = 3.35, 95% CI = 1.09-10.30). In secondary analyses, each
doubling of IL-6 change over 20 years was associated with greater odds of
cognitive impairment in 2009-2010 in the whole cohort (odds ratio (OR) = 1.40,
95% CI = 1.04-1.89), whereas a doubling of CRP change over 20 years was
associated with cognitive impairment only in statin nonusers (OR = 1.32, 95% CI =
1.06-1.65). CONCLUSION: With data collected over 20 years, this study
demonstrated greater likelihood of cognitive impairment in individuals with
repeated high or increasing IL-6. The inconsistent CRP findings may reflect
effects of statin medications, survival effects, or adverse effects associated
with chronically low CRP. Further studies of long-term inflammation and cognitive
impairment are needed.
PMID- 25123214
TI - Contrasting electrogenerated chemiluminescence for a dissolved and surface
attached carbazole thiophene cyanoacrylate dye.
AB - The electrogenerated chemiluminescence (ECL) of a carbazole thiophene
cyanoacrylate dye ((2-cyano-3-[5"'-(9-ethyl-9H-carbazol-3-yl)-3',3",3"',4-tetra-n
hexyl-[2,2',5',2",5",2"']-quarter-thiophenyl-5yl]acrylate) = MK-2) has been
investigated in solution, where the maximum ECL wavelength occurs at 640 nm, and
in a thin film on an ITO surface, where the ECL is substantially red-shifted to
730 nm. The ECL intensity for the solution annihilation reaction is relatively
weak, whereas a much higher ECL intensity is measured with oxalate as a co
reactant. This result is attributed to the two Nernstian reversible oxidation
waves of the thiophene moiety of MK-2, whereas the reduction is stabilized by the
unblocked carbazole and cyanoacrylate groups.
PMID- 25123212
TI - Baby steps: investigating the development of perceptual-motor couplings in
infancy.
AB - There are cells in our motor cortex that fire both when we perform and when we
observe similar actions. It has been suggested that these perceptual-motor
couplings in the brain develop through associative learning during correlated
sensorimotor experience. Although studies with adult participants have provided
support for this hypothesis, there is no direct evidence that associative
learning also underlies the initial formation of perceptual-motor couplings in
the developing brain. With the present study we addressed this question by
manipulating infants' opportunities to associate the visual and motor
representation of a novel action, and by investigating how this influenced their
sensorimotor cortex activation when they observed this action performed by
others. Pre-walking 7-9-month-old infants performed stepping movements on an
infant treadmill while they either observed their own real-time leg movements
(Contingent group) or the previously recorded leg movements of another infant
(Non-contingent control group). Infants in a second control group did not perform
any steps and only received visual experience with the stepping actions. Before
and after the training period we measured infants' sensorimotor alpha
suppression, as an index of sensorimotor cortex activation, while they watched
videos of other infants' stepping actions. While we did not find greater
sensorimotor alpha suppression following training in the Contingent group as a
whole, we nevertheless found that the strength of the visuomotor contingency
experienced during training predicted the amount of sensorimotor alpha
suppression at post-test in this group. We did not find any effects of motor
experience alone. These results suggest that the development of perceptual-motor
couplings in the infant brain is likely to be supported by associative learning
during correlated visuomotor experience.
PMID- 25123215
TI - Compression force on the upper jaw during neonatal intubation: mannequin study.
AB - AIM: Neonatal intubation is a technically challenging procedure, and pressure
related injuries to surrounding structures have been reported. The primary
objective of this study was to determine the pressure exerted on the upper jaw
during tracheal intubation using a neonatal mannequin. METHOD: Multidisciplinary
care providers working at a neonatal intensive care unit were requested to
intubate a neonatal mannequin using the standard laryngoscope and 3.0-mm
(internal diameter) endotracheal tube. Compression force exerted was measured by
using pressure-sensitive film taped on the upper jaw before every intubation
attempt. Pressure, area under pressure and time taken to intubate were compared
between the different types of health-care professionals. RESULTS: Thirty care
providers intubated the mannequin three times each. Pressure impressions were
observed on the developer film after every intubation attempt (n = 90). The mean
pressure exerted during intubation across all health-care providers was 568 kPa
(SD 78). The mean area placed under pressure was 142 mm(2) (SD 45), and the mean
time taken for intubation was 14.7 s (SD 4.3). There was no difference in
pressure exerted on the upper jaw between frequent and less frequent intubators.
It was found that pressure greater than 400 kPa was inadvertently applied on the
upper jaw during neonatal intubation, far exceeding the 250 kPa shown to cause
tissue injury in animal models. CONCLUSION: The upper jaw is exposed to a
significant compression force during intubation. Although such exposure is brief,
it has the potential to cause tissue injury. Contact of the laryngoscope blade
with the upper jaw occurred in all intubation attempts with the currently used
design of laryngoscope.
PMID- 25123213
TI - Epidemiology and clinical characteristics of autoimmune hepatitis in the
Netherlands.
AB - BACKGROUND AND AIMS: Epidemiological data on autoimmune hepatitis (AIH) are
scarce. In this study, we determined the clinical and epidemiological
characteristics of AIH patients in the Netherlands (16.7 million inhabitants).
METHODS: Clinical characteristics were collected from 1313 AIH patients (78%
females) from 31 centers, including all eight academic centers in the
Netherlands. Additional data on ethnicity, family history and symptoms were
obtained by the use of a questionnaire. RESULTS: The prevalence of AIH was 18.3
(95% confidential interval [CI]: 17.3-19.4) per 100,000 with an annual incidence
of 1.1 (95% CI: 0.5-2) in adults. An incidence peak was found in middle-aged
women. At diagnosis, 56% of patients had fibrosis and 12% cirrhosis in liver
biopsy. Overall, 1% of patients developed HCC and 3% of patients underwent liver
transplantation. Overlap with primary biliary cirrhosis and primary sclerosing
cholangitis was found in 9% and 6%, respectively. The clinical course did not
differ between Caucasian and non-Caucasian patients. Other autoimmune diseases
were found in 26% of patients. Half of the patients reported persistent AIH
related symptoms despite treatment with a median treatment period of 8 years
(range 1-44 years). Familial occurrence was reported in three cases. CONCLUSION:
This is the largest epidemiological study of AIH in a geographically defined
region and demonstrates that the prevalence of AIH in the Netherlands is
uncommon. Although familial occurrence of AIH is extremely rare, our twin data
may point towards a genetic predisposition. The high percentage of patients with
cirrhosis or fibrosis at diagnosis urges the need of more awareness for AIH.
PMID- 25123216
TI - Letter by Kirchoff-Torres and Labovitz regarding article, "Lifelong rupture risk
of intracranial aneurysms depends on risk factors: a prospective Finnish cohort
study".
PMID- 25123218
TI - Response to letter regarding article, "Lifelong rupture risk of intracranial
aneurysms depends on risk factors: a prospective Finnish cohort study".
PMID- 25123217
TI - Twelve-single nucleotide polymorphism genetic risk score identifies individuals
at increased risk for future atrial fibrillation and stroke.
AB - BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is prevalent and there is a
clinical need for biomarkers to identify individuals at higher risk for AF. Fixed
throughout a life course and assayable early in life, genetic biomarkers may meet
this need. Here, we investigate whether multiple single nucleotide polymorphisms
together as an AF genetic risk score (AF-GRS) can improve prediction of one's
risk for AF. METHODS: In 27 471 participants of the Malmo Diet and Cancer Study,
a prospective, community-based cohort, we used Cox models that adjusted for
established AF risk factors to assess the association of AF-GRS with incident AF
and ischemic stroke. Median follow-up was 14.4 years for incident AF and 14.5
years for ischemic stroke. The AF-GRS comprised 12 single nucleotide
polymorphisms that had been previously shown to be associated with AF at genome
wide significance. RESULTS: During follow-up, 2160 participants experienced a
first AF event and 1495 had a first ischemic stroke event. Participants in the
top AF-GRS quintile were at increased risk for incident AF (hazard ratio, 2.00;
95% confidence interval, 1.73-2.31; P=2.7*10(-21)) and ischemic stroke (hazard
ratio, 1.23; 95% confidence interval, 1.04-1.46; P=0.02) when compared with the
bottom quintile. Addition of the AF-GRS to established AF risk factors modestly
improved both discrimination and reclassification (P<0.0001 for both).
CONCLUSIONS: An AF-GRS can identify 20% of individuals who are at ~2-fold
increased risk for incident AF and at 23% increased risk for ischemic stroke.
Targeting diagnostic or therapeutic interventions to this subset may prove
clinically useful.
PMID- 25123219
TI - Circuit class therapy and 7-day-week therapy increase physiotherapy time, but not
patient activity: early results from the CIRCIT trial.
AB - BACKGROUND AND PURPOSE: The optimum model of physiotherapy service delivery for
maximizing active task practice during rehabilitation after stroke is unknown.
The purpose of the study was to examine the relative effectiveness of 2
alternative models of physiotherapy service delivery against a usual care control
with regard to increasing patient activity. METHODS: Substudy within a large 3
armed randomized controlled trial, which compared 3 different models of
physiotherapy service delivery, was provided for 4 weeks during subacute,
inpatient rehabilitation (n=283). The duration of all physiotherapy sessions was
recorded. In addition, 32 participants were observed at 10-minute intervals for 1
weekday and 1 weekend day between 8:00 am and 4:30 pm. At each observation, we
recorded physical activity, location, and people present. RESULTS: Participants
receiving 7-day-week and circuit class therapy received an additional 3 hours and
22 hours of physiotherapy time, respectively, when compared with usual care.
Participants were standing or walking for a median of 8.2% of observations. On
weekdays, circuit class therapy participants spent more time in therapy-related
activity (10.2% of observations) when compared with usual care participants (6.1%
of observations). On weekends, 7-day therapy participants spent more time in
therapy-related activity (4.2% of observations) when compared with both usual
care and circuit class therapy participants (0% of observations for both groups).
Activity levels outside of therapy sessions did not differ between groups.
CONCLUSIONS: A greater dosage of physiotherapy time did not translate into
meaningful increases in physical activity across the day. CLINICAL TRIAL
REGISTRATION URL: http://www.anzctr.org.au/. Unique identifier:
ACTRN12610000096055.
PMID- 25123220
TI - Combined effects of socioeconomic position, smoking, and hypertension on risk of
ischemic and hemorrhagic stroke.
AB - BACKGROUND AND PURPOSE: Combined effects of socioeconomic position and well
established risk factors on stroke incidence have not been formally investigated.
METHODS: In a pooled cohort study of 68 643 men and women aged 30 to 70 years in
Denmark, we examined the combined effect and interaction between socioeconomic
position (ie, education), smoking, and hypertension on ischemic and hemorrhagic
stroke incidence by the use of the additive hazards model. RESULTS: During 14
years of follow-up, 3613 ischemic strokes and 776 hemorrhagic strokes were
observed. Current smoking and hypertension were more prevalent among those with
low education. Low versus high education was associated with greater ischemic,
but not hemorrhagic, stroke incidence. The combined effect of low education and
current smoking was more than expected by the sum of their separate effects on
ischemic stroke incidence, particularly among men: 134 (95% confidence interval,
49-219) extra cases per 100 000 person-years because of interaction, adjusted for
age, cohort study, and birth cohort. There was no clear evidence of interaction
between low education and hypertension. The combined effect of current smoking
and hypertension was more than expected by the sum of their separate effects on
ischemic and hemorrhagic stroke incidence. This effect was most pronounced for
ischemic stroke among women: 178 (95% confidence interval, 103-253) extra cases
per 100 000 person-years because of interaction, adjusted for age, cohort study,
and birth cohort. CONCLUSIONS: Reducing smoking in those with low socioeconomic
position and in those with hypertension could potentially reduce social
inequality stroke incidence.
PMID- 25123221
TI - Better health, less spending: delivery innovation for ischemic cerebrovascular
disease.
PMID- 25123223
TI - Statin therapy for venous ulcers.
PMID- 25123222
TI - Low levels of low-density lipoprotein-C associated with proprotein convertase
subtilisin kexin 9 inhibition do not increase the risk of hemorrhagic
transformation.
AB - BACKGROUND AND PURPOSE: Low levels of low-density lipoprotein-cholesterol (LDL-C)
are suspected to be associated with a risk of hemorrhagic transformation after
ischemic stroke. We assessed the risk of hemorrhagic transformation after
cerebral ischemia/reperfusion in mice with low levels of LDL-C resulting from
proprotein convertase subtilisin kexin 9 (PCSK9) deficiency. METHODS: PCSK9-/-
and PCSK9+/+ mice were fed with a high-fat/high-cholesterol (21%/0.15%) diet for
1 month. Plasma lipids were measured using colorimetric assays. PCSK9-/- and
PCSK9+/+ mice (n=15 per group) were subjected to a 4-hour intraluminal occlusion
of the middle cerebral artery followed by 20 hours of reperfusion. Spontaneous
hemorrhagic transformation was assessed by quantification of hemoglobin in
ischemic tissue. In vitro, a cell model of blood-brain barrier was used to test
endothelial barrier integrity in response to decreasing concentrations of LDL-C
from 1 to 0.25g/L in ischemia/reperfusion conditions. RESULTS: PCSK9-/- mice had
lower LDL-C, high-density lipoprotein-cholesterol, and total cholesterol levels
than PCSK9+/+ mice before and after 1 month on the high-fat/high-cholesterol
diet. Hemoglobin concentration in ischemic cerebral tissue was not different
between PCSK9-/- and PCSK9+/+ mice (31.5 [18.9-60.1] and 32.8 [14.7-69.9] ng/mg
protein, respectively; P=0.81). Infarct volume was also similar in both groups
(P=0.66). Incubation of human cerebral endothelial cells with decreasing
concentrations of LDL-C under ischemia/reperfusion conditions did not alter blood
brain barrier permeability. CONCLUSIONS: Low levels of LDL-C did not increase the
risk of hemorrhagic transformation after cerebral ischemia/reperfusion in mice.
Our observations suggest that PCSK9 inhibition, leading to LDL-C lowering, should
not increase hemorrhagic complications after acute ischemic stroke.
PMID- 25123224
TI - Pneumocyte injury and ubiquitin-positive pneumocytes in interstitial lung
diseases.
AB - Pneumocyte injury is a characteristic of pulmonary interstitial pneumonias (IPs).
Histological markers of pneumocyte injury and inflammation include pneumocyte
necrosis, erosion, hyaline membrane and fibrin exudation with subsequent
intraluminal granulation tissue formation. We found that intracytoplasmic
inclusions in pneumocytes are ubiquitin-positive (Ub(+) ) and that the number of
Ub(+) pneumocytes shows positive correlation with the extent of diffuse alveolar
damage (DAD). To determine the role of Ub(+) pneumocytes and inclusions in IPs,
we studied their relationship with pathological and clinical features of DAD,
usual interstitial pneumonia (UIP) and organizing pneumonia (OP), including
airspace enlargement with fibrosis (AEF). We analysed Ub(+) pneumocytes,
inclusions, erosions and intraluminal granulation tissue in relation to
pneumocyte injury. The numbers of immunohistochemically identified Ub(+)
inclusions in each IP were higher than the number of inclusions detected by light
microscopy. The inclusions detected by Ub(+) immunostaining were identical to the
inclusions observed by light microscopy. UIP and DAD had many Ub(+) inclusions,
while OP and AEF had fewer Ub(+) inclusions. These results suggest that the
extent of Ub(+) inclusions reflects the severity of pneumocyte injury among IPs.
Thus, Ub(+) inclusions are a histological marker of pneumocyte injury that may be
helpful in determining the severity and prognosis of IPs.
PMID- 25123226
TI - Assessment of ocular pain following ranibizumab intravitreal injection.
PMID- 25123225
TI - Synthetic biology approaches to improve biocatalyst identification in metagenomic
library screening.
AB - There is a growing demand for enzymes with improved catalytic performance or
tolerance to process-specific parameters, and biotechnology plays a crucial role
in the development of biocatalysts for use in industry, agriculture, medicine and
energy generation. Metagenomics takes advantage of the wealth of genetic and
biochemical diversity present in the genomes of microorganisms found in
environmental samples, and provides a set of new technologies directed towards
screening for new catalytic activities from environmental samples with potential
biotechnology applications. However, biased and low level of expression of
heterologous proteins in Escherichia coli together with the use of non-optimal
cloning vectors for the construction of metagenomic libraries generally results
in an extremely low success rate for enzyme identification. The bottleneck
arising from inefficient screening of enzymatic activities has been addressed
from several perspectives; however, the limitations related to biased expression
in heterologous hosts cannot be overcome by using a single approach, but rather
requires the synergetic implementation of multiple methodologies. Here, we review
some of the principal constraints regarding the discovery of new enzymes in
metagenomic libraries and discuss how these might be resolved by using synthetic
biology methods.
PMID- 25123227
TI - Genetic alterations of chromosome 8 genes in oral cancer.
AB - The clinical relevance of DNA copy number alterations in chromosome 8 were
investigated in oral cancers. The copy numbers of 30 selected genes in 33 OSCC
patients were detected using the multiplex ligation-dependent probe amplification
(MLPA) technique. Amplifications of the EIF3E gene were found in 27.3% of the
patients, MYC in 18.2%, RECQL4 in 15.2% and MYBL1 in 12.1% of patients. The most
frequent gene losses found were the GATA4 gene (24.2%), FGFR1 gene (24.2%), MSRA
(21.2) and CSGALNACT1 (12.1%). The co-amplification of EIF3E and RECQL4 was found
in 9% of patients and showed significant association with alcohol drinkers. There
was a significant association between the amplification of EIF3E gene with non
betel quid chewers and the negative lymph node status. EIF3E amplifications did
not show prognostic significance on survival. Our results suggest that EIF3E may
have a role in the carcinogenesis of OSCC in non-betel quid chewers.
PMID- 25123229
TI - Avoiding perceived past resource use of potential competitors affects niche
dynamics in a bird community.
AB - BACKGROUND: Social information use is usually considered to lead to ecological
convergence among involved con- or heterospecific individuals. However, recent
results demonstrate that observers can also actively avoid behaving as those
individuals being observed, leading to ecological divergence. This phenomenon has
been little explored so far, yet it can have significant impact on resource use,
realized niches and species co-existence. In particular, the time-scale and the
ecological context over which such shifts can occur are unknown. We examined with
a long-term (four years) field experiment whether experimentally manipulated,
species-specific, nest-site feature preferences (symbols on nest boxes) are
transmitted across breeding seasons and affect future nest-site preferences in a
guild of three cavity-nesting birds. RESULTS: Of the examined species, resident
great tits (Parus major) preferred the symbol that had been associated with
unoccupied nest boxes in the previous year, i.e., their preference shifted
towards niche space previously unused by putative competitors and conspecifics.
CONCLUSIONS: Our results show that animals can remember the earlier resource use
of conspecifics and other guild members and adjust own decisions accordingly one
year after. Our experiment cannot reveal the ultimate mechanism(s) behind the
observed behaviour but avoiding costs of intra- or interspecific competition or
ectoparasite load in old nests are plausible reasons. Our findings imply that
interspecific social information use can affect resource sharing and realized
niches in ecological time-scale through active avoidance of observed decisions
and behavior of potentially competing species.
PMID- 25123228
TI - Cyclic phosphatidic acid relieves osteoarthritis symptoms.
AB - BACKGROUND: Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid
mediator with a unique cyclic phosphate ring at the sn-2 and sn-3 positions of
its glycerol backbone. Natural cPA and its chemically stabilized cPA derivative,
2-carba-cPA (2ccPA), inhibit chronic and acute inflammation, and 2ccPA attenuates
neuropathic pain. Osteoarthritis (OA) is a degenerative disease frequently
associated with symptoms such as inflammation and joint pain. Because 2ccPA has
obvious antinociceptive activity, we hypothesized that 2ccPA might relieve the
pain caused by OA. We aimed to characterize the effects of 2ccPA on the
pathogenesis of OA induced by total meniscectomy in the rabbit knee joint.
RESULTS: Intra-articular injection of 2ccPA (twice a week for 42 days)
significantly reduced pain and articular swelling. Histopathology showed that
2ccPA suppressed cartilage degeneration in OA. We also examined the effects of
2ccPA on the inflammatory and catabolic responses of human OA synoviocytes and
chondrosarcoma SW1353 cells in vitro. 2ccPA stimulated synthesis of hyaluronic
acid and suppressed production of the metalloproteinases MMP-1, -3, and -13.
However, it had no effect on the production of interleukin (IL)-6, an
inflammatory cytokine. The suppressive effect of 2ccPA on MMP-1 and -3 production
in synoviocytes and on MMP-13 production in SW1353 cells was not mediated by the
lysophosphatidic acid receptor, LPA1 receptor (LPA1R). CONCLUSIONS: Our results
suggest that 2ccPA significantly reduces the pain response to OA by inducing
hyaluronic acid production and suppressing MMP-1, -3, and -13 production in
synoviocytes and chondrocytes.
PMID- 25123230
TI - The (cost) effectiveness of an online intervention for pregnant women with
affective symptoms: protocol of a randomised controlled trial.
AB - BACKGROUND: Women in pregnancy and postpartum have an increased vulnerability to
develop an affective disorder. Affective disorders in pregnancy are associated
with an increased risk of prematurity, dysmaturity (foetal weight below the 10th
percentile as determined by ultrasound) and the development of postpartum
depressive disorder. Untreated affective disorders and their complications may
also result in considerable costs. Recent meta-analyses showed that interventions
during pregnancy are less effective than postpartum interventions probably
because of high attrition due to the barriers pregnant women experience with
attending sessions outside their homes. An internet-based self-help intervention
may overcome these barriers as it can be followed at home, and also in one's own
time. Such internet interventions showed to be effective for decreasing affective
symptoms in general.This randomised clinical trial examines whether an internet
based self-help intervention is effective in the reduction of affective symptoms
in pregnancy and postpartum and results in an improvement of the perinatal
outcome. We will also determine the cost-effectiveness of the intervention.
METHODS/DESIGN: We will investigate the effectiveness of a 6 week internet-based
self-help problem solving treatment (PST) for affective symptoms in pregnancy. We
aim to include 286 women with mild to severe affective symptoms who will be
randomly assigned to the internet-based intervention or a waiting list control
group. Primary outcome measures are affective symptoms and the perinatal outcome.
Secondary outcome measures are quality of life, and economic costs. All
assessments are based on self-report and will take place at baseline (T0), 10
weeks later (after completion of the intervention (T1), 4 weeks before the
expected day of birth (T2), and 6 weeks after delivery (T3). The control group
will be measured at the same moments in time. Analysis will be based on the
intention-to-treat principle. DISCUSSION: If shown (cost) effective, internet
based PST will offer new possibilities to treat pregnant women for affective
symptoms, to improve their perinatal outcome and to prevent the development of
postpartum depressive disorders. TRIAL REGISTRATION: Nederlands Trial Register:
NTR4321.
PMID- 25123232
TI - What is the association of heme aggregates with the peritrophic matrix of adult
female mosquitoes?
AB - The aim of this Letter is to call attention to the presence of iron-containing or
heme aggregates seen within or near the peritrophic matrix (PM) in published
Anopheles gambiae and Aedes aegypti midgut micrographs. The micrographs shown
here suggest that the PM of An. gambiae adult female is not a homogenous layer
and instead may have a peritrophin layer surrounded by heme aggregates that are
possibly associated to other molecules involved in their formation. In depth
studies addressing PM structure in different mosquito species are needed, as
these will be important to continue clarifying the roles of the PM.
PMID- 25123233
TI - Cost-effectiveness analysis of endoscopic sphenopalatine artery ligation vs
arterial embolization for intractable epistaxis.
AB - IMPORTANCE: Intractable epistaxis is a common otolaryngology emergency.
Transnasal endoscopic sphenopalatine artery ligation (TESPAL) and endovascular
arterial embolization both provide excellent success rates, and therefore the
decision to choose one over the other can be challenging. OBJECTIVE: To aid in
decision making by evaluating the cost-effectiveness of TESPAL vs endovascular
arterial embolization for intractable epistaxis. DESIGN, SETTING, AND
PARTICIPANTS: Economic evaluation using a decision tree model with a 14-day time
horizon for emergency department consultations for patients with intractable
epistaxis defined as persistent bleeding despite bilateral anterior nasal
packing. The economic perspective was the health care third-party payer.
Effectiveness and probability data were obtained from the published medical
literature. Costs were obtained from the published literature, the Centers for
Medicare & Medicaid Services database, and the Healthcare Cost and Utilization
Project database. Multiple sensitivity analyses were performed, including a
probabilistic sensitivity analysis. Comparative treatment groups were (1) TESPAL
and (2) embolization. INTERVENTIONS: TESPAL and endovascular arterial
embolization. MAIN OUTCOME AND MEASURES: The primary outcome was the incremental
cost-effectiveness ratio (ICER) for successful control of epistaxis. RESULTS: The
reference case demonstrated that the embolization strategy was more effective but
more costly compared with the TESPAL strategy: $22,324.70 per 0.70 effectiveness
compared with $12,484.14 per 0.68 of effectiveness, respectively. The
embolization vs TESPAL ICER was $492,028, which is higher than any willingness to
pay (WTP), suggesting that TESPAL is the cost-effective decision. The sensitivity
analysis demonstrated a 77.6% and 73.7% certainty that the TESPAL strategy is
cost-effective at WTP thresholds of $10,000 and $50,000, respectively.
CONCLUSIONS AND RELEVANCE: Results from this economic evaluation suggest that
when both TESPAL and arterial embolization are viable options (based on patient
and institutional factors), TESPAL is the more cost-effective treatment strategy
for patients with intractable epistaxis.
PMID- 25123231
TI - Modeling the dependence of respiration and photosynthesis upon light, acetate,
carbon dioxide, nitrate and ammonium in Chlamydomonas reinhardtii using design of
experiments and multiple regression.
AB - BACKGROUND: In photosynthetic organisms, the influence of light, carbon and
inorganic nitrogen sources on the cellular bioenergetics has extensively been
studied independently, but little information is available on the cumulative
effects of these factors. Here, sequential statistical analyses based on design
of experiments (DOE) coupled to standard least squares multiple regression have
been undertaken to model the dependence of respiratory and photosynthetic
responses (assessed by oxymetric and chlorophyll fluorescence measurements) upon
the concomitant modulation of light intensity as well as acetate, CO2, nitrate
and ammonium concentrations in the culture medium of Chlamydomonas reinhardtii.
The main goals of these analyses were to explain response variability (i.e.
bioenergetic plasticity) and to characterize quantitatively the influence of the
major explanatory factor(s). RESULTS: For each response, 2 successive rounds of
multiple regression coupled to one-way ANOVA F-tests have been undertaken to
select the major explanatory factor(s) (1st-round) and mathematically simulate
their influence (2nd-round). These analyses reveal that a maximal number of 3
environmental factors over 5 is sufficient to explain most of the response
variability, and interestingly highlight quadratic effects and second-order
interactions in some cases. In parallel, the predictive ability of the 2nd-round
models has also been investigated by k-fold cross-validation and experimental
validation tests on new random combinations of factors. These validation
procedures tend to indicate that the 2nd-round models can also be used to predict
the responses with an inherent deviation quantified by the analytical error of
the models. CONCLUSIONS: Altogether, the results of the 2 rounds of modeling
provide an overview of the bioenergetic adaptations of C. reinhardtii to changing
environmental conditions and point out promising tracks for future in-depth
investigations of the molecular mechanisms underlying the present observations.
PMID- 25123234
TI - A pilot prospective study to evaluate whether the bladder morphology in
cystography and/or urodynamic may help predict the response to botulinum toxin a
injection in neurogenic bladder refractory to anticholinergics.
AB - BACKGROUND: We have observed different clinical responses to botulinum toxin A
(BTX-A) in patients who had similar urodynamic parameters before the procedure.
Furthermore, some bladders evaluated by cystography and cystoscopy during the
procedure had different characteristics that could influence the outcome of the
treatment. The aim of this study was to assess whether cystography and urodynamic
parameters could help predict which patients with neurogenic detrusor
overactivity (NDO) refractory to anticholinergics respond better to treatment
with injection of BTX-A. METHODS: In total, 34 patients with spinal cord injury
were prospectively evaluated. All patients emptied their bladder by clean
intermittent catheterization (CIC) and had incontinence and NDO, despite using 40
mg or more of intravesical oxybutynin and undergoing detrusor injection of BTX-A
(300 IU). Pretreatment evaluation included urodynamic, and cystography. Follow-up
consisted of urodynamic and ambulatory visits four months after treatment. The
cystography parameters used were bladder shape, capacity and presence of
diverticula. Urodynamic parameters used for assessment were maximum cystometric
capacity (MCC), maximum detrusor pressure (MDP), compliance and reflex volume
(RV). RESULTS: After injection of BTX-A, 70% of the patients had success, with 4
months or more of continence. Before the treatment, there were significant
differences in most urodynamic parameters between those who responded
successfully compared to those who did not. Patients who responded successfully
had greater MCC (p = 0.019), higher RV (p = 0.041), and greater compliance (p =
0.043). There was no significant difference in the MDP (0.691). The cystography
parameters were not significantly different between these groups bladder shape (p
= 0.271), capacity (p > 0.720) and presence of diverticula (p > 0.999).
Statistical analyses were performed using SPSS (version 20.0) and included
Student's t-test for two paired samples and Fisher's exact test, with a
significance threshold of 0.05. CONCLUSIONS: This study suggests that the
cystography parameters evaluated cannot be used to help predict the response to
injection of BTX-A in the treatment of refractory NDO. However, the urodynamic
parameters were significantly different in patients who responded to the
treatment, with the exception of the MDP.
PMID- 25123236
TI - Similar differentiation patterns between PBP expression levels and pheromone
component ratios in two populations of Sesamia nonagrioides.
AB - Pheromone-binding proteins (PBPs) are thought to contribute to the specificity of
the pheromone detection system through an initial selective binding with
pheromone molecules. Here, we report different expression levels of PBP
transcripts in the antennae of two populations of the stemborer Sesamia
nonagrioides (Lepidoptera: Noctuidae), one collected in Europe and one in sub
Saharan Africa. The three PBP transcripts previously identified in this species
were found to be expressed in both male and female antennae. Whereas PBP3 did not
show any differential expression, PBP1 and PBP2 appeared to be expressed
differently according to the population origin and sex. Simultaneously, we
measured and compared the ratio of the three components of the S. nonagrioides
pheromone blend (Z11-16:Ac; Z11-16:OH; Z11-16:Ald) in females of the two
populations. The ratio of Z11-16:OH and Z11-16:Ald varied significantly according
to the population origin of this species. Cluster analyses revealed similar
differentiation patterns between PBP1 and PBP2 expression levels and the ratios
of Z11-16:OH and Z11-16:Ald. Different female sexual signals may thus correspond
to different male reception systems, which are adjusted by the PBP expression
levels, thereby ensuring optimal communication within populations.
PMID- 25123235
TI - Topically applied ZnO nanoparticles suppress allergen induced skin inflammation
but induce vigorous IgE production in the atopic dermatitis mouse model.
AB - BACKGROUND: Metal oxide nanoparticles such as ZnO are used in sunscreens as they
improve their optical properties against the UV-light that causes dermal damage
and skin cancer. However, the hazardous properties of the particles used as UV
filters in the sunscreens and applied to the skin have remained uncharacterized.
METHODS: Here we investigated whether different sized ZnO particles would be able
to penetrate injured skin and injured allergic skin in the mouse atopic
dermatitis model after repeated topical application of ZnO particles. Nano-sized
ZnO (nZnO) and bulk-sized ZnO (bZnO) were applied to mechanically damaged mouse
skin with or without allergen/superantigen sensitization. Allergen/superantigen
sensitization evokes local inflammation and allergy in the skin and is used as a
disease model of atopic dermatitis (AD). RESULTS: Our results demonstrate that
only nZnO is able to reach into the deep layers of the allergic skin whereas bZnO
stays in the upper layers of both damaged and allergic skin. In addition, both
types of particles diminish the local skin inflammation induced in the mouse
model of AD; however, nZnO has a higher potential to suppress the local effects.
In addition, especially nZnO induces systemic production of IgE antibodies,
evidence of allergy promoting adjuvant properties for topically applied nZnO.
CONCLUSIONS: These results provide new hazard characterization data about the
metal oxide nanoparticles commonly used in cosmetic products and provide new
insights into the dermal exposure and hazard assessment of these materials in
injured skin.
PMID- 25123237
TI - Prevalence and drug resistance of mycobacteria in Turkish cystic fibrosis
patients.
AB - BACKGROUND: Isolation of mycobacteria in cystic fibrosis (CF) patients is
increasingly being reported. Because of having long term antimicrobial treatment,
CF patients are at risk of pulmonary infection with especially resistant
nontuberculous mycobacteria (NTM) strains. The aim of the present study is to
determine the prevalence of mycobacterium spp. and antimicrobial susceptibility
in Turkish CF patients. METHODS: During a 5.5 year study period, 376 sputa from
130 CF patients were analyzed. Antimycobacterial susceptibility testing was
performed by the Bactec 460 TB System and the E test method. RESULTS: Totaly 28
(7.44%) Mycobacterium spp. were isolated from eight (6.15%) CF patients. Five
isolates (17.9%) were identified as Mycobacterium tuberculosis complex (MTBC), 14
(50%) as Mycobacterium abscessus and nine (32.1%) as Mycobacterium lentiflavum.
All MTBC isolates were found to be susceptible to streptomycin, isoniazid,
rifampicin, and ethambutol. Resistance to some antibiotics was detected in some
NTM strains. These are the first data about the prevalence of mycobacteria in CF
patients from Turkey. CONCLUSIONS: In pediatric CF patients, specific
mycobacterial analysis of sputum specimens and susceptibility testing should be
performed for allowing early detection, identification and the possibility of
eradication of these bacteria.
PMID- 25123238
TI - Intravenous iron sucrose: an alternative for oral iron in pregnancy with iron
deficiency anemia.
PMID- 25123239
TI - The John Charnley Award: Highly crosslinked polyethylene in total hip
arthroplasty decreases long-term wear: a double-blind randomized trial.
AB - BACKGROUND: The use of highly crosslinked polyethylene (HXLPE) is now commonplace
for total hip arthroplasty. Hip simulator studies and short-term in vivo
measurements suggest that the wear rate of some types of HXLPE is significantly
less than conventional ultrahigh-molecular-weight polyethylene (UHMWPE). However,
there are few long-term data to support its use. QUESTIONS/PURPOSES: The aim of
this study was to measure the long-term steady-state wear of HXLPE compared with
UHMWPE liners in a prospective, double-blind, randomized controlled trial using
radiostereometric analysis. METHODS: Fifty-four patients were randomized to
receive hip arthroplasties with either UHMWPE liners or HXLPE liners. Complete
followup was available on 39 of these patients (72%). All patients received the
same cemented stem and an uncemented acetabular component. Three-dimensional
penetration of the head into the socket was determined at 10 years using a
radiostereometric analysis system, which has an in vivo accuracy of <0.1 mm.
Oxford Hip Scores were compared between the groups. RESULTS: At 10 years there
was significantly less wear of HXLPE (0.003 mm/year; 95% confidence interval
[CI], +/-0.010; SD 0.023; range, -0.057 to 0.074) compared with UHMWPE (0.030
mm/year; 95% CI, +/-0.012; p<0.001; SD 0.0.27; range, -0.001 to 0.164). The
volumetric penetration from 1 to 10 years for the UHMWPE group was 98 mm3 (95%
CI, +/-46 mm3; SD 102 mm3; range, -4 to 430 mm3) compared with 14 mm3 (95% CI, +/
40 mm3; SD 91 mm3; range, -189 to 242 mm3) for the HXLPE group (p=0.01).
CONCLUSIONS: This study demonstrates that HXLPE has little detectable steady
state in vivo wear. This may result in fewer reoperations from loosening;
however, careful clinical followup into the second decade still needs to be
performed. LEVEL OF EVIDENCE: Level I, therapeutic study. See the Guidelines for
Authors for a complete description of levels of evidence.
PMID- 25123240
TI - Does HIV infection increase the risk of perioperative complications after THA? A
nationwide database study.
AB - BACKGROUND: Recent studies have shown successful midterm outcomes after total hip
arthroplasty (THA) in patients with human immunodeficiency virus (HIV). However,
little data exist on the epidemiology, risk of perioperative complications, and
length of stay in patients with HIV receiving THA. QUESTIONS/PURPOSES: The
purposes of this study were to assess (1) the demographic trends of patients with
HIV who underwent primary THA; (2) the differences in the risk of major and minor
perioperative complications among patients with and without HIV; and (3) the
differences in mean length of hospital stay among patients with and without HIV.
METHODS: The Nationwide Inpatient Sample was used to compare patients with and
without HIV who were admitted for THA between 1998 and 2010 in the United States.
We extracted data on each admission's age, sex, race, insurance, and
comorbidities. The study population consisted of 2,656,696 patients without HIV
and 9275 patients with HIV. RESULTS: Patients with HIV were more likely to be
younger, be male, not pay with Medicare, and be of a nonwhite race. After
controlling for confounding variables, patients with HIV were more likely to have
major complications (2.9% [266 of 9275] versus 2.7% [71,952 of 2,656,696]; odds
ratio [OR], 1.47; 95% confidence interval [CI], 1.08-2.00; p=0.014) and minor
complications (5.2% [483 of 9275] versus 4.8% [127,940 of 2,656,696]; OR, 1.61;
95% CI, 1.29-2.02; p<0.001) compared with patients who did not have HIV. Patients
undergoing THA who had HIV also had an increased length of hospital stay compared
with patients without HIV (4.31 versus 3.83 days, p<0.001). CONCLUSIONS: Given
these findings, we believe orthopaedic surgeons should be aware of the potential
for longer and more complicated hospital stays after THA among patients with HIV.
However, the modest increase in risk of adverse outcomes does not cause us to
recommend against THA for patients with HIV who otherwise meet reasonable
surgical indications. Future studies should explore the relationships between
markers of HIV severity and risk of adverse outcomes after THA during the
hospital stay and followup. LEVEL OF EVIDENCE: Level III, therapeutic study. See
Guidelines for Authors for a complete description of levels of evidence.
PMID- 25123241
TI - Continued good results with modular trabecular metal augments for acetabular
defects in hip arthroplasty at 7 to 11 years.
AB - BACKGROUND: Reconstruction of large acetabular defects remains a substantial
challenge in hip arthroplasty. There remains a paucity of data on the long-term
results of acetabular trabecular metal augments. QUESTIONS/PURPOSES: The purpose
of this study was to assess the survivorship, clinical outcomes, restoration of
center of rotation of the hip, and radiological signs of component fixation of
trabecular metal augments in the context of reconstruction of acetabular defects.
METHODS: Between 2002 and 2005, we performed 56 revision (n=53) and primary (n=3)
THAs using trabecular metal augments in combination with a trabecular metal
acetabular component. Of the 56 patients, 16 (29%) died during followup. Of the
40 surviving patients, 37 (93%) had complete radiological followup, 23 (58%) had
complete outcome questionnaire followup, and 17 (42%) provided partial
questionnaire responses in the clinic or over the telephone. Median followup was
110 months (range, 88-128 months). During that period, we used these implants
when preoperative templating indicated that an augment would be required to
achieve acetabular implant stability with restoration of the hip center of
rotation. We also chose during surgery to use an augment when we could not
achieve a stable acetabular trial component without one. The combination of
trabecular metal augments and trabecular metal shells was used in 18% (53 of 292)
of our acetabular revisions during that time. Survivorship, functional outcome
(WOMAC and Oxford hip score), health status (SF-12), and osseointegration
according to the criteria of Moore and presence of radiolucencies were
determined. RESULTS: Survivorship of the augments at 10 years was 92% (95%
confidence interval, 81%-97%). Four patients underwent cup revision, one for
infection and three for loosening. The mean WOMAC global score was 79 (SD 17),
the mean Oxford hip score 76 (SD 18), the mean physical component SF-12 score was
39 (SD 11), and the mean mental component SF-12 score was 52 (SD 9). The center
of rotation was corrected from more than 35 mm above the inter-teardrop line in
48 of 56 patients preoperatively to only five of 46 postoperatively. One patient
had radiographic findings suggestive of loosening, but this patient was
asymptomatic. CONCLUSIONS: The results of the acetabular trabecular metal
augments continue to be encouraging in the medium to long term with low rates of
revision or loosening in this complex group of patients. We continue to recommend
the use of these augments in the reconstruction of complex acetabular defects.
LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors
for a complete description of levels of evidence.
PMID- 25123242
TI - CORR Insights(r): minorities are less likely to receive autologous blood
transfusion for major elective orthopaedic surgery.
PMID- 25123243
TI - Do corresponding authors take responsibility for their work? A covert survey.
AB - BACKGROUND: Publication of a manuscript does not end an author's
responsibilities. Reasons to contact an author after publication include
clarification, access to raw data, and collaboration. However, legitimate
questions have been raised regarding whether these responsibilities generally are
being met by corresponding authors of biomedical publications.
QUESTIONS/PURPOSES: This study aims to establish (1) what proportion of
corresponding authors accept the responsibility of correspondence; (2) identify
characteristics of responders; and (3) assess email address decay with time. We
hypothesize that the response rate is unrelated to journal impact factor.
METHODS: We contacted 450 corresponding authors throughout various fields of
biomedical research regarding the availability of additional data from their
study, under the pretense of needing these data for a related review article.
Authors were randomly selected from 45 journals whose impact factors ranged from
52 to 0; the source articles were published between May 2003 and May 2013. The
proportion of corresponding authors who replied, along with author
characteristics were recorded, as was the proportion of emails that were returned
for inactive addresses; 446 authors were available for final analysis. RESULTS:
Fifty-three percent (190/357) of the authors with working email addresses
responded to our request. Clinical researchers were more likely to reply than
basic/translational scientists (51% [114/225] versus 34% [76/221]; p<0.001).
Impact factor and other author characteristics did not differ. Logistic
regression analysis showed that the odds of replying decreased by 15% per year
(odds ratio [OR], 0.85; 95% CI, 0.79-0.91; p<0.001), and showed a positive
relationship between clinical research and response (OR, 2.0; 95% CI, 1.3-2.9;
p=0.001). In 2013 all email addresses (45/45) were reachable, but within 10
years, 49% (21/43) had become invalid. CONCLUSIONS: Our results suggest that
contacting corresponding authors is problematic throughout the field of
biomedical research. Defining the responsibilities of corresponding authors by
journals more explicitly-particularly after publication of their manuscript-may
increase the response rate on data requests. Possible other ways to improve
communication after research publication are: (1) listing more than one email
address per corresponding author, eg, an institutional and personal address; (2)
specifying all authors' email addresses; (3) when an author leaves an
institution, send an automated reply offering alternative ways to get in touch;
and (4) linking published manuscripts to research platforms.
PMID- 25123244
TI - Cochrane in CORR(r): surgery for rotator cuff disease (review).
PMID- 25123245
TI - Thigh pain in an 18-year-old man.
PMID- 25123246
TI - Editorial comment: 2013Musculoskeletal Infection Society meeting.
PMID- 25123247
TI - CORR Insights(r): does advanced cryotherapy reduce pain and narcotic consumption
after knee arthroplasty?
PMID- 25123249
TI - A significant inhibitory effect on advanced glycation end product formation by
catechin as the major metabolite of lotus seedpod oligomeric procyanidins.
AB - Several lines of evidence suggested that B-type procyanidin oligomers from lotus
seedpod (LSOPC) may effectively modulate the formation of advanced glycation end
products (AGEs). In vivo, LSOPC is metabolized by intestinal flora to become
various kinds of phenolic compounds that possess potent antioxidant activities.
However, few reports of the absorption and metabolism of LSOPC have been
revealed. In the present study, rats were orally administered with LSOPC at a
dose of 300 mg/kg body weight. The metabolites of LSOPC in urine were elucidated
by HPLC-MS/MS analysis 24 h post-administration. Eight major metabolites were
significantly increased by the administration of 300 mg/kg of LSOPC (p < 0.01).
The anti-glycative activity of LSOPC and its metabolites were investigated. The
results showed that LSOPC and catechin had greater anti-glycative activities than
other metabolites, which were positively correlated to their carbonyl scavenging
activities and antioxidant capacities.
PMID- 25123248
TI - Vitamin E supplementation in chemical colorectal carcinogenesis: a two-edged
knife.
AB - This work investigated the effects of Vitamin E (VE) on aberrant crypt foci (ACF)
incidence, oxidative stress parameters (serum and hepatic VE concentration, and
homocysteine, glutathione (GSH), and malondialdehyde (MDA) levels), and
expression of both cyclooxygenase-2 (COX2) and proliferating cellular nuclear
antigen (PCNA) in experimental colorectal carcinogenesis. Male Wistar rats
received subcutaneous injections of 1,2-dimethylhydrazine (DMH) twice a week, for
two weeks (40 mg/kg), except for the Control group. Animals were separated into
groups that received different amounts of VE in the diet: 0 IU (0*), 75 IU
(recommended daily intake, RDI), 225 IU (3* RDI), or 1500 IU (20* RDI), during
(dDMH) or after (aDMH) administration of carcinogen. The 0*dDMH and 3*dDMH groups
showed decreased serum VE levels. Hepatic VE concentration was higher in 3*aDMH
as compared with the other groups. All the groups, except the Control and the
0*aDMH groups, had reduced GSH levels. The 0*dDMH, 0*aDMH, and 20*aDMH groups
exhibited increased MDA levels. The aDMH groups had higher ACF incidence and PCNA
expression. The 0*aDMH group presented higher ACF rate, followed by 20*aDMH.
Moreover, the 3*aDMH group displayed reduced ACF incidence and COX2 expression.
Multivariate analysis revealed that GSH modulated homocysteine levels and COX2.
These results suggested that 1500 IU of VE is hazardous, whereas 225 IU of VE has
beneficial effects on chemical colorectal carcinogenesis.
PMID- 25123251
TI - Etiopathogenesis of acquired cholesteatoma: prominent theories and recent
advances in biomolecular research.
AB - OBJECTIVE: To review recent biomolecular advances in etiopathogenesis of acquired
cholesteatoma. DATA SOURCES: MEDLINE via OVID (to March 2014) and PubMed (to
March 2014). REVIEW METHODS: All articles referring to etiopathogenesis of
acquired cholesteatoma were identified in the above databases, from which 89
articles were included in this review. RESULTS: The mechanisms underlying the
etiopathogenesis of acquired cholesteatoma remain a subject of competing
hypotheses. Four theories dominate the debate, including theories of
invagination, immigration, squamous metaplasia, and basal cell hyperplasia.
However, no single theory has been able to explain the clinical characteristics
of all cholesteatoma types: uncoordinated hyperproliferation, invasion,
migration, altered differentiation, aggressiveness, and recidivism. Modern
technologies have prompted a number of researchers to seek explanations at the
molecular level. First, cholesteatomas could be considered an example of
uncontrolled cell growth, capable of altering the balance toward cellular
hyperproliferation and enhancing the capacity for invasion and osteolysis.
Second, the dysregulation of cell growth control involves internal genomic or
epigenetic alterations and external stimuli, which induce excessive host immune
response to inflammatory and infectious processes. This comprises several complex
and dynamic pathophysiologic changes that involve extracellular and intracellular
signal transduction cascades. CONCLUSIONS: This article summarizes the existing
theories and provides conceptual insights into the etiopathogenesis of acquired
cholesteatoma, with the aim of stimulating continued efforts to develop a
nonsurgical means of treating the disorder.
PMID- 25123252
TI - In vitro performance and principles of anti-siphoning devices.
AB - BACKGROUND: Anti-siphon devices (ASDs) of various working principles were
developed to overcome overdrainage-related complications associated with
ventriculoperitoneal shunting. OBJECTIVE: We aimed to provide comparative data on
the pressure and flow characteristics of six different types of ASDs (gravity
assisted, membrane-controlled, and flow-regulated) in order to achieve a better
understanding of these devices and their potential clinical application. METHODS:
We analyzed three gravity-dependent ASDs (ShuntAssistant [SA], Miethke; Gravity
Compensating Accessory [GCA], Integra; SiphonX [SX], Sophysa), two membrane
controlled ASDs (Anti-Siphon Device [IASD], Integra; Delta Chamber [DC],
Medtronic), and one flow-regulated ASD (SiphonGuard [SG], Codman). Defined
pressure conditions within a simulated shunt system were generated (differential
pressure 10-80 cmH2O), and the specific flow and pressure characteristics were
measured. In addition, the gravity-dependent ASDs were measured in defined
spatial positions (0-90 degrees ). RESULTS: The flow characteristics of the three
gravity-assisted ASDs were largely dependent upon differential pressure and on
their spatial position. All three devices were able to reduce the siphoning
effect, but each to a different extent (flow at inflow pressure: 10 cmH2O,
siphoning -20 cmH2O at 0 degrees /90 degrees : SA, 7.1 +/- 1.2*/2.3 +/- 0.5*
ml/min; GCA, 10.5 +/- 0.8/3.4 +/- 0.4* ml/min; SX, 9.5 +/- 1.2*/4.7 +/- 1.9*
ml/min, compared to control, 11.1 +/- 0.4 ml/min [*p < 0.05]). The flow
characteristics of the remaining ASDs were primarily dependent upon the inflow
pressure effect (flow at 10 cmH2O, siphoning 0 cmH2O/ siphoning -20cmH2O: DC, 2.6
+/- 0.1/ 4 +/- 0.3* ml/min; IASD, 2.5 +/- 0.2/ 0.8 +/- 0.4* ml/min; SG, 0.8 +/-
0.2*/ 0.2 +/- 0.1* ml/min [*p < 0.05 vs. control, respectively]). CONCLUSION: The
tested ASDs were able to control the siphoning effect within a simulated shunt
system to differing degrees. Future comparative trials are needed to determine
the type of device that is superior for clinical application.
PMID- 25123250
TI - Lipoic acid plays a role in scleroderma: insights obtained from scleroderma
dermal fibroblasts.
AB - INTRODUCTION: Systemic sclerosis (SSc) is a connective tissue disease
characterized by fibrosis of the skin and organs. Increase in oxidative stress
and platelet-derived growth factor receptor (PDGFR) activation promote collagen I
(Col I) production, leading to fibrosis in SSc. Lipoic acid (LA) and its active
metabolite dihydrolipoic acid (DHLA) are naturally occurring thiols that act as
cofactors and antioxidants, and are produced by lipoic acid synthetase (LIAS).
The goal of this study was to examine whether LA and LIAS was deficient in SSc
patients and determine the effect of DHLA on the phenotype of SSc dermal
fibroblasts. N-acetylcysteine (NAC), a commonly used thiol antioxidant, was
included as a comparison. METHODS: Dermal fibroblasts were isolated from healthy
subjects and patients with diffuse cutaneous SSc. Matrix metalloproteinase
(MMPs), tissue inhibitors of MMPs (TIMP), plasminogen activator inhibitor-1 (PAI
1) and LIAS were measured by ELISA. The expression of Col I was measured by
immunofluorescence, hydroxyproline assay, and quantitative PCR. PDGFR
phosphorylation and alpha-smooth muscle actin (alpha-SMA) was measured by Western
blotting. Student's t-tests were performed for statistical analysis and p-values
of less than 0.05 with two-tailed analysis were considered statistically
significant. RESULTS: The expression of LA and LIAS in SSc dermal fibroblasts was
lower than normal fibroblasts, however LIAS was significantly higher in SSc
plasma and appeared to be released from monocytes. DHLA lowered cellular
oxidative stress, and decreased PDGFR phosphorylation, Col I, PAI-1, and alpha
SMA expression in SSc dermal fibroblasts. It also restored the activities of
phosphatases that inactivated the PDGFR. SSc fibroblasts produced lower levels of
MMP-1 and 3, and DHLA increased them. In contrast, TIMP-1 levels were higher in
SSc but DHLA had minimal effect. Both DHLA and NAC increased MMP-1 activity when
SSc cells were stimulated with PDGF. In general, DHLA showed better efficacy than
NAC in most cases. CONCLUSIONS: DHLA not only acts as an antioxidant but also an
antifibrotic since it has the ability to reverse the profibrotic phenotype of SSc
dermal fibroblasts. Our study suggests that thiol antioxidants, including NAC and
LA/DHLA, could be beneficial for patients with SSc.
PMID- 25123253
TI - Clinical COPD Questionnaire in patients with chronic respiratory disease.
AB - BACKGROUND AND OBJECTIVE: The Clinical Chronic Obstructive Pulmonary Disease
(COPD) Questionnaire (CCQ) is an easy to complete, health-related quality of life
questionnaire which has been well-validated in COPD. The responsiveness of the
CCQ in chronic respiratory disease patients other than COPD has not been
previously described. The study aims were to determine if the CCQ in chronic
respiratory disease correlates with other health related quality of life
questionnaires, to assess the responsiveness of the CCQ to pulmonary
rehabilitation and to determine the minimum important difference. METHODS: The
CCQ, COPD Assessment Test (CAT), the Chronic Respiratory Questionnaire (CRQ) and
St George's Respiratory Questionnaire (SGRQ) were measured in 138 chronic
respiratory disease patients completing pulmonary rehabilitation. Change in CCQ
with pulmonary rehabilitation was correlated with change in the other
questionnaires. The minimum important difference of the CCQ was calculated using
distribution and anchor-based approaches. RESULTS: The CCQ, CAT, CRQ and SGRQ
improved significantly with rehabilitation with effect sizes of -0.43, -0.26,
0.62, -0.37. Change in CCQ correlated significantly with CAT, CRQ and SGRQ (r =
0.53, -0.64, 0.30, all P < 0.0001). The minimum important difference was -0.42 at
the population level and -0.4 at the individual level. CONCLUSIONS: The CCQ is
responsive to pulmonary rehabilitation in chronic respiratory disease patients,
with an MID estimated at -0.4 at the individual level.
PMID- 25123254
TI - Poor neonatal acid-base status in term fetuses with low cerebroplacental ratio.
AB - OBJECTIVE: To determine whether small- and appropriate-for-gestational-age (SGA
and AGA) term fetuses with a low cerebroplacental ratio (CPR) have worse neonatal
acid-base status than those with normal CPR. METHODS: This was a retrospective
study of 2927 term fetuses divided into groups according to birth-weight centile
and CPR multiple of the median. The acid-base status at birth as determined by
arterial and venous umbilical cord blood pH was compared between weight-centile
groups with and without low CPR. RESULTS: CPR was better correlated with
umbilical cord blood pH (arterial pH, r(2) = 0.008, P < 0.0001 and venous pH,
r(2) = 0.01, P < 0.0001) than was birth weight (arterial pH, r(2) = 0.001, P
=0.180 and venous pH, r(2) = 0.005, P < 0.001). AGA fetuses with low CPR were
more academic than were those with normal CPR (P = 0.0359 and 0.0006,
respectively, for arterial and venous pH). CONCLUSIONS: The findings of this
study demonstrate that low CPR in AGA fetuses is an equally important marker of
low neonatal pH secondary to placental underperfusion as is being SGA. Although
the relative importance of low CPR and birth weight in identifying pregnancies at
risk of placental hypoxemia and adverse fetal and neonatal outcome remains to be
determined, this finding may be of particular value in the prediction and
prevention of stillbirth and long-term neurodevelopmental disability.
PMID- 25123256
TI - Similar hypotensive effects of combined aerobic and resistance exercise with 1
set versus 3 sets in women with metabolic syndrome.
AB - The aim of the present study was to compare the response of systolic blood
pressure (SBP), mean blood pressure (MBP) and diastolic blood pressure (DBP)
following combined training with 1 set or with 3 sets of resistance exercise
(RE). Sixteen women with metabolic syndrome (MetS) were randomly assigned to
perform two combined exercise protocols and a control session (CON): 1-set, 30
min of aerobic exercise (AE) at 65-70% of reserve heart rate and 1 set of 8-12
repetitions at 80% of 10-RM in six resistance exercises; 3-sets, same protocol
but with 3 sets; and CON, 30 min of seated rest. The SBP, MBP and DBP were
measured before and every 15 min during 90 min following the experimental
sessions. The SBP displayed a decrease (P <= 0.05) during the 90 min following
the RE session with 1-set and 3-set, while MBP was decreased (P <= 0.05) up to 75
min after 1-set and up to 30 min after the 3-set exercise session compared with
pre-intervention values. There was a decrease in DBP only for the greatest
individual decrease following 1-set (-6.1 mmHg) and 3-set (-4.9 mmHg) combined
exercise sessions, without differences between them. The rate-pressure product
and heart rate remained significantly higher (P <= 0.05) 75 min and 90 min after
the combined exercise session with 1- and 3-sets compared with the CON,
respectively. In conclusion, a low-volume RE combined with AE resulted in similar
decrease of SBP when compared with RE with 3-sets in women with MetS, which could
be beneficial in situations of limited time.
PMID- 25123255
TI - CHARGE-like presentation, craniosynostosis and mild Mowat-Wilson Syndrome
diagnosed by recognition of the distinctive facial gestalt in a cohort of 28 new
cases.
AB - Mowat-Wilson syndrome (MWS) is characterized by moderate to severe intellectual
disability and distinctive facial features in association with variable
structural congenital anomalies/clinical features including congenital heart
disease, Hirschsprung disease, hypospadias, agenesis of the corpus callosum,
short stature, epilepsy, and microcephaly. Less common clinical features include
ocular anomalies, craniosynostosis, mild intellectual disability, and choanal
atresia. These cases may be more difficult to diagnose. In this report, we add 28
MWS patients with molecular confirmation of ZEB2 mutation, including seven with
an uncommon presenting feature. Among the "unusual" patients, two patients had
clinical features of charge syndrome including choanal atresia, coloboma, cardiac
defects, genitourinary anomaly (1/2), and severe intellectual disability; two
patients had craniosynostosis; and three patients had mild intellectual
disability. Sixteen patients have previously-unreported mutations in ZEB2.
Genotype-phenotype correlations were suggested in those with mild intellectual
disability (two had a novel missense mutation in ZEB2, one with novel splice site
mutation). This report increases the number of reported patients with MWS with
unusual features, and is the first report of MWS in children previously thought
to have CHARGE syndrome. These patients highlight the importance of facial
gestalt in the accurate identification of MWS when less common features are
present.
PMID- 25123257
TI - Periodontal therapy for the management of cardiovascular disease in patients with
chronic periodontitis.
AB - BACKGROUND: There is an association between chronic periodontitis and
cardiovascular disease (CVD). However, it is not known whether periodontal
therapy could prevent or manage CVD in patients with chronic periodontitis.
OBJECTIVES: The objective of this systematic review was to investigate the
effects of periodontal therapy in preventing the occurrence of, and management or
recurrence of, CVD in patients with chronic periodontitis. SEARCH METHODS: The
electronic databases that were searched were the Cochrane Oral Health Group's
Trials Register (to 7 April 2014), the Cochrane Central Register of Controlled
Trials (CENTRAL) (The Cochrane Library 2014, Issue 3), MEDLINE via OVID (1946 to
7 April 2014), EMBASE via OVID (1980 to 7 April 2014), CINAHL via EBSCO (1937 to
7 April 2014), OpenGrey (to 7 April 2014), the Chinese BioMedical Literature
Database (1978 to April 2014), the China National Knowledge Infrastructure (1994
to April 2014) and the VIP database (1989 to April 2014). We searched the US
National Institutes of Health Trials Register, the World Health Organization
(WHO) Clinical Trials Registry Platform and Sciencepaper Online for ongoing
trials. No restrictions were placed on the language or date of publication when
searching the electronic databases. SELECTION CRITERIA: Randomised controlled
trials (RCTs) and quasi-RCTs were considered eligible. Studies were selected if
they included patients with a diagnosis of chronic periodontitis and previous CVD
(secondary prevention studies) or no CVD (primary prevention studies); patients
in the intervention group received active periodontal therapy compared to
maintenance therapy, no periodontal treatment or another kind of periodontal
treatment in the control group. DATA COLLECTION AND ANALYSIS: Two review authors
carried out the study identification, data extraction and risk of bias assessment
independently and in duplicate. Any discrepancies between the two authors were
resolved by discussion or with a third review author. A formal pilot-tested data
extraction form was adopted for the data extraction, and the Cochrane
Collaboration's tool for risk of bias assessment was used for the critical
appraisal of the literature. MAIN RESULTS: No studies were identified that
assessed primary prevention of CVD in people with periodontitis. One study
involving 303 participants with >= 50% blockage of one coronary artery or a
coronary event within three years, but not the three months prior, was included.
The study was at high risk of bias due to deviation from the protocol treatment
allocation and lack of follow-up data. The trial compared scaling and root
planing (SRP) with community care for a follow-up period of six to 25 months. No
data on deaths (all-cause or CVD-related) were reported. There was insufficient
evidence to determine the effect of SRP and community care in reducing the risk
of CVD recurrence in patients with chronic periodontitis (risk ratio (RR) 0.72;
95% confidence interval (CI) 0.23 to 2.22; very low quality evidence). The
effects of SRP compared with community care on high-sensitivity C-reactive
protein (hs-CRP) (mean difference (MD) 0.62; -1.45 to 2.69), the number of
patients with high hs-CRP (RR 0.77; 95% CI 0.32 to 1.85) and adverse events (RR
9.06; 95% CI 0.49 to 166.82) were also not statistically significant. The study
did not assess modifiable cardiovascular risk factors, other blood test results,
heart function parameters or revascularisation procedures. AUTHORS' CONCLUSIONS:
We found very low quality evidence that was insufficient to support or refute
whether periodontal therapy can prevent the recurrence of CVD in the long term in
patients with chronic periodontitis. No evidence on primary prevention was found.
PMID- 25123258
TI - Precession electron diffraction-assisted crystal phase mapping of metastable c
GaN films grown on (001) GaAs.
AB - The control growth of the cubic meta-stable nitride phase is a challenge because
of the crystalline nature of the nitrides to grow in the hexagonal phase, and
accurately identifying the phases and crystal orientations in local areas of the
nitride semiconductor films is important for device applications. In this study,
we obtained phase and orientation maps of a metastable cubic GaN thin film using
precession electron diffraction (PED) under scanning mode with a point-to-point 1
nm probe size beam. The phase maps revealed a cubic GaN thin film with hexagonal
GaN inclusions of columnar shape. The orientation maps showed that the inclusions
have nucleation sites at the cubic GaN {111} facets. Different growth
orientations of the inclusions were observed due to the possibility of the
hexagonal {0001} plane to grow on any different {111} cubic facet. However, the
generation of the hexagonal GaN inclusions is not always due to a 60 degrees
rotation of a {111} plane. These findings show the advantage of using PED along
with phase and orientation mapping, and the analysis can be extended to
differently composed semiconductor thin films.
PMID- 25123259
TI - Fatty acid desaturase 1 gene polymorphisms control human hepatic lipid
composition.
AB - Fatty acid desaturase (FADS) genes and their variants have been associated with
multiple metabolic phenotypes, including liver enzymes and hepatic fat
accumulation, but the detailed mechanism remains unclear. We aimed to delineate
the role of FADSs in modulating lipid composition in human liver. We performed a
targeted lipidomic analysis of a variety of phospholipids, sphingolipids, and
ceramides among 154 human liver tissue samples. The associations between
previously genome-wide association studies (GWASs)-identified six FADS single
nucleotide polymorphisms (SNPs), and these lipid levels as well as total hepatic
fat content (HFC) were tested. The potential function of these SNPs in regulating
transcription of three FADS genes (FADS1, FADS2, and FADS3) in the locus was also
investigated. We found that though these SNPs were in high linkage disequilibrium
(r(2) > 0.8), the rare alleles of these SNPs were consistently and significantly
associated with the accumulation of multiple long-chain fatty acids (LCFAs), with
C47H85O13P (C36:4), a phosphatidylinositol (PI), and C43H80O8PN (C38:3), a
phosphatidylethanolamine (PE), reached the Bonferroni corrected significance (P <
3 * 10(-4)). Meanwhile, these SNPs were significantly associated with increased
ratios between the more saturated and relatively less saturated forms of LCFAs,
especially between PEs, PIs, and phosphatidylcholines (PCs; P <= 3.5 * 10(-6)).
These alleles were also associated with increased total HFC (P < 0.05). Further
analyses revealed that these alleles were associated with decreased hepatic
expression of FADS1 (P = 0.0018 for rs174556), but not FADS2 or FADS3 (P > 0.05).
CONCLUSION: Our findings revealed critical insight into the mechanism underlying
FADS1 and its polymorphisms in modulating hepatic lipid deposition by altering
gene transcription and controlling lipid composition in human livers.
PMID- 25123260
TI - Long-term phenological trends, species accumulation rates, aphid traits and
climate: five decades of change in migrating aphids.
AB - Aphids represent a significant challenge to food production. The Rothamsted
Insect Survey (RIS) runs a network of 12.2-m suction-traps throughout the year to
collect migrating aphids. In 2014, the RIS celebrated its 50th anniversary. This
paper marks that achievement with an extensive spatiotemporal analysis and the
provision of the first British annotated checklist of aphids since 1964. Our main
aim was to elucidate mechanisms that advance aphid phenology under climate change
and explain these using life-history traits. We then highlight emerging pests
using accumulation patterns. Linear and nonlinear mixed-effect models estimated
the average rate of change per annum and effects of climate on annual counts,
first and last flights and length of flight season since 1965. Two climate
drivers were used: the accumulated day degrees above 16 degrees C (ADD16)
indicated the potential for migration during the aphid season; the North Atlantic
Oscillation (NAO) signalled the severity of the winter before migration took
place. All 55 species studied had earlier first flight trends at rate of beta =
0.611 +/- SE 0.015 days year(-1). Of these species, 49% had earlier last flights,
but the average species effect appeared relatively stationary (beta = -0.010 +/-
SE 0.022 days year(-1)). Most species (85%) showed increasing duration of their
flight season (beta = 0.336 +/- SE 0.026 days year(-1)), even though only 54%
increased their log annual count (beta = 0.002 +/- SE <0.001 year(-1)). The ADD16
and NAO were shown to drive patterns in aphid phenology in a spatiotemporal
context. Early in the year when the first aphids were migrating, the effect of
the winter NAO was highly significant. Further into the year, ADD16 was a strong
predictor. Latitude had a near linear effect on first flights, whereas longitude
produced a generally less-clear effect on all responses. Aphids that are
anholocyclic (permanently parthenogenetic) or are monoecious (non-host
alternating) were advancing their phenology faster than those that were not.
Climate drives phenology and traits help explain how this takes place
biologically. Phenology and trait ecology are critical to understanding the
threat posed by emerging pests such as Myzus persicae nicotianae and Aphis fabae
cirsiiacanthoidis, as revealed by the species accumulation analysis.
PMID- 25123261
TI - The application of micro-vacuo-certo-contacting ophthalmophanto in X-ray
radiosurgery for tumors in an eyeball.
AB - The large errors of routine localization for eyeball tumors restricted X-ray
radiosurgery application, just for the eyeball to turn around. To localize the
accuracy site, the micro-vacuo-certo-contacting ophthalmophanto (MVCCOP) method
was used. Also, the outcome of patients with tumors in the eyeball was evaluated.
In this study, computed tomography (CT) localization accuracy was measured by
repeating CT scan using MVCCOP to fix the eyeball in radiosurgery. This study
evaluated the outcome of the tumors and the survival of the patients by follow
up. The results indicated that the accuracy of CT localization of Brown-Roberts
Wells (BRW) head ring was 0.65 mm and maximum error was 1.09 mm. The accuracy of
target localization of tumors in the eyeball using MVCCOP was 0.87 mm averagely,
and the maximum error was 1.19 mm. The errors of fixation of the eyeball were
0.84 mm averagely and 1.17 mm maximally. The total accuracy was 1.34 mm, and 95%
confidence accuracy was 2.09 mm. The clinical application of this method in 14
tumor patients showed satisfactory results, and all of the tumors showed the
clear rims. The site of ten retinoblastomas was decreased significantly. The
local control interval of tumors were 6 ~ 24 months, median of 10.5 months. The
survival of ten patients was 7 ~ 30 months, median of 16.5 months. Also, the
tumors were kept stable or shrank in the other four patients with angioma and
melanoma. In conclusion, the MVCCOP is suitable and dependable for X-ray
radiosurgery for eyeball tumors. The tumor control and survival of patients are
satisfactory, and this method can effectively postpone or avoid extirpation of
eyeball.
PMID- 25123262
TI - Lipase member H is a novel secreted protein associated with a poor prognosis for
breast cancer patients.
AB - The objective of this study is to identify the expression status and clinical
implications of lipase member H (LIPH) in breast cancer in order to develop
strategies for breast cancer management. LIPH expression status was detected in
346 breast cancer specimens by immunohistochemistry. The relationship between
LIPH expression, clinico-pathological parameters, and prognosis of breast cancer
was determined. LIPH expression was higher in breast cancer specimens than in
paracarcinoma tissues (P=0.01). In total, 64.74% (224/346) of breast cancer
samples had high expression of the LIPH protein. LIPH was related to tumor size,
histological grade, lymph node metastasis, and distant metastasis (P=0.073,
0.001, 0.001, and 0.001, respectively). Furthermore, individuals with high LIPH
expression had a significantly higher rate of distant metastasis and poorer
disease-specific survival than those with no or low LIPH expression (P=0.01). A
Cox regression test indicated that the LIPH protein was an independent prognostic
factor (P=0.001). LIPH was differentially expressed in breast cancer individuals
and is an independent prognostic factor for breast cancer as well as a potential
target for its management.
PMID- 25123263
TI - Matrix metalloproteinase-7 mRNA and protein expression in gastric carcinoma: a
meta-analysis.
AB - Messenger RNA (mRNA) acts as template for protein synthesis. The matrix
metalloproteinase-7 (MMP-7) protein and its mRNA expression have been suggested
to be involved in the development of various diseases and cancers. We aimed to
study associations between the MMP-7 protein and mRNA expression in gastric
carcinoma (GC) patients. We searched in the Science Citation Index, the Cochrane
Library, PubMed, Embase, CINAHL, Current Contents Index, and several Chinese
databases. Studies were pooled and odds ratios and their corresponding 95 %
confidence intervals were calculated. Subgroup analyses and publication bias
detection were also conducted. Statistical analysis was performed via Version
12.0 STATA software. An updated meta-analysis based on 16 independent cohort
studies was performed to investigate this association. The study suggests that
significant differences in MMP-7 protein levels were observed in tumor-node
metastasis (TNM) I-II vs. III-IV (odds radio (OR) =3.19, 95 % confidence interval
(95%CI) =1.59 ~ 6.41, P=0.001), in T1-2 vs. T3-4 invasive grade (OR=1.82,
95%CI=1.07 ~ 3.12, P=0.028), and in distant metastasis-positive vs. metastasis
negative samples (OR=3.14, 95%CI=1.05 ~ 9.35, P=0.040). Increased MMP-7 mRNA
levels were found to be significantly correlated with invasive grade (T3-4 vs. T1
2: OR=5.61, 95%CI=2.64 ~ 11.95, P<0.001) and in the lymph node (LN) metastasis
(positive vs. negative: OR=7.08, 95%CI=4.20 ~ 11.93, P<0.001) group. Country
subgroup analysis yielded significantly different estimates in the protein
expression of MMP-7 of all experimental groups. MMP-7 mRNA levels were increased
in LN metastasis-positive GC in contrast to metastasis-negative in China and
Korea (all P<0.05); this was not shown in Japan (P>0.05). Higher protein and mRNA
levels of MMP-7 were statistically associated with aggressive LN metastasis,
advanced TNM stage, and invasion in GC patients; MMP-7 can thus potentially serve
as a useful biomarker in determining GC progression and prognosis.
PMID- 25123264
TI - High expression of UCH37 is significantly associated with poor prognosis in human
epithelial ovarian cancer.
AB - Ubiquitin carboxyl-terminal hydrolase 37 (UCH37) is a member of deubiquitinating
enzymes. It can suppress protein degradation through disassembling polyubiquitin
from the distal subunit of the chain. The aim of this study was to assess the
value of UCH37 in predicting tumor recurrence after curative resection in
epithelial ovarian cancer (EOC) patients. In this study, the expression level of
UCH37 in 5 paired EOC and normal tissue was tested by Western blot. And the
association of UCH37 expression and prognostic value was analyzed in 100 tumor
specimens from EOC patients, who underwent curative resection between 2003 and
2011. We found that UCH37 was up-regulated in most of the tumor tissue and high
expression of UCH37 was an independent significant predictor associated with the
poor outcome and recurrence of EOC (p=0.0037 and p=0.0042 in overall and disease
free survival, respectively), especially in the advanced stage of EOC (p=0.0106
and p=0.0115 in overall and disease-free survival, respectively), and may become
a novel predictor for prognosis of EOC patients after curative resection. Our
data suggest for the first time that UCH37 overexpression is associated with
advanced tumor progression and poor clinical outcome of EOC patients and may help
physicians make informed decisions regarding adjuvant treatment following
curative resection.
PMID- 25123265
TI - Plasma interleukin-11 (IL-11) levels have diagnostic and prognostic roles in
patients with pancreatic cancer.
AB - Interleukin-11 (IL-11) affects inflammation, motility, and invasion in cancer.
Here, we investigated the clinical significance of plasma IL-11 (IL-11p) levels
in patients with pancreatic cancer. We enrolled 44 patients with pathologically
confirmed diagnoses of pancreatic cancer into this study (median age at
diagnosis, 68 years; range, 42-86 years), along with 30 age- and sex-matched
healthy controls and 3 patients with pancreatitis complicated with pancreatic
cysts and 15 patients with early pancreatitis. Median baseline IL-11p levels of
patients with pancreatic cancer were significantly higher than that of the
healthy controls (P < 0.001), as were those of the 15 patients with early
pancreatitis. IL-11p levels presented high diagnostic accuracy for pancreatic
cancer (area under the curve (AUC), 0.901; sensitivity, 97.7%; specificity,
70.0%). Age, sex, lesion site, disease stage, serum dehydrogenase, alkaline
phosphatase, gamma-glutamyltransferase, and white blood cells, platelets, and
hemoglobin levels did not correlate with IL-11p concentrations (P>0.05), but
patients with distant metastases had lower median IL-11p values than did patients
without distant metastases (P=0.043). Patients with IL-11p higher than the median
level (43.2 pg/mL) had better prognoses than those with lower values (P=0.004),
particularly as IL-11p concentration increased to >= 50 pg/mL (P=0.001). IL-11p
concentration correlated with overall survival (>= median IL-11p, 10 months;
0.05). UCA1 can be
used as a non-invasive diagnostic biomarker for TCC bladder as an adjunct to
cytology in the early diagnosis of primary urinary bladder cancer.
PMID- 25123268
TI - miR-203a regulates proliferation, migration, and apoptosis by targeting glycogen
synthase kinase-3beta in human renal cell carcinoma.
AB - MicroRNAs play a crucial role in cancer progression and metastasis. miR-203a has
been identified as a tumor suppressor in various cancers. However, its functions
in renal cell carcinoma have not been illustrated. In this study, we detected the
miR-203a expression in renal cell carcinoma and evaluated its association with
clinical features. Overexpression of miR-203a was found in renal cell carcinoma
tissues and renal cell carcinoma cells. High miR-203a expression is correlated
with tumor stage and short overall survival time. Bioinformatics and luciferase
assay confirmed that glycogen synthase kinase-3beta was a target gene of miR
203a. Silencing of miR-203a could inhibit cell proliferation and migration,
arrest them in G1 phase, and promote apoptosis in vitro. miR-203a promotes the
progression of renal cell carcinoma and predicts a poor prognosis.
PMID- 25123269
TI - Genetic variants in the KDR gene is associated with the prognosis of
transarterial chemoembolization treated hepatocellular carcinoma.
AB - Kinase insert domain receptor (KDR) is the principal receptor that promotes the
proangiogenic action of vascular endothelial growth factor and is involved in the
tumorigenesis and progression of many malignancies, including hepatocellular
carcinoma (HCC). Single-nucleotide polymorphisms (SNPs) of KDR have been reported
to be with the risk and prognosis of several malignancies. Our aim was to
determine whether SNPs in KDR gene are associated with clinical outcomes in HCC
patients treated with transcatheter arterial chemoembolization. A total of 192
HCC patients were tested for KDR SNPs, and the SNP results were correlated with
progression-free survival (PFS) and overall survival (OS). The association of the
SNPs with the overall survival (OS) of patients was assessed by Kaplan-Meier
method, and then Cox proportional hazards model was used to assess the variables
resulted significant at univariate analysis. No significant differences were
found in correlation between KDR SNPs and patients' PFS. Our data showed that
genotype AA+TA of rs1870377 and genotype CC+TC of rs2071559 were significantly
associated with overall survival of HCC patients (P<0.001 and P<0.001,
respectively) and remained as significant predictors for OS adjusting for high
level of serum AFP (>400 MUg/L), existence of portal vein tumor thrombus, and
high BCLC stage (HR=0.61; 95% CI, 0.36-0.88; P=0.003 and HR=0.54; 95% CI, 0.40
0.94; P=0.002, respectively). Our results suggest that SNPs rs1870377 and
rs2071559 in the KDR gene may serve as independent prognosis biomarkers for
unresectable HCC patient, which warranted further validating investigation.
PMID- 25123271
TI - A systematic review and meta-analysis of perineural dexamethasone for peripheral
nerve blocks.
AB - We systematically reviewed the safety and efficacy of perineural dexamethasone as
an adjunct for peripheral nerve blockade in 29 controlled trials of 1695
participants. We grouped trials by the duration of local anaesthetic action
(short- or medium- vs long-term). Dexamethasone increased the mean (95% CI)
duration of analgesia by 233 (172-295) min when injected with short- or medium
term action local anaesthetics and by 488 (419-557) min when injected with long
term action local anaesthetics, p < 0.00001 for both. However, these results
should be interpreted with caution due to the extreme heterogeneity of results,
with I2 exceeding 90% for both analyses. Meta-regression did not show an
interaction between dose of perineural dexamethasone (4-10 mg) and duration of
analgesia (r2 = 0.02, p = 0.54). There were no differences between 4 and 8 mg
dexamethasone on subgroup analysis.
PMID- 25123272
TI - Size dependence of the upconverted luminescence of NaYF4:Er,Yb microspheres for
use in ratiometric thermometry.
AB - The size-dependent temperature sensitivity is observed on the upconversion
luminescence of NaYF4:Er,Yb microspheres with sizes between 0.7 and 2 MUm that
are prepared by a poly(acrylic acid)-assisted hydrothermal process. It is found
that the fluorescence intensity ratio (FIR) of their green upconversion emissions
(with peaks at 521 and 539 nm) is strongly size-dependent at temperatures between
223 and 403 K. As the size of the spheres increases from 0.7 to 1.6 MUm, the
maximum sensitivity decreases from 36.8 * 10(-4) to 24.7 * 10(-4) K(-1). This
effect is mainly attributed to the larger specific surface area of the smaller
spheres where a relatively large number of Er(III) ions are located at the
surface. This results in an increase in the efficiency of the (4)S3/2 -> (2)H11/2
population process of the Er(III) ions due to stronger electron-phonon
interactions with increasing T. Heating of the spheres by NIR light is also
supposed to cause enhanced electron-phonon interactions in such particles.
PMID- 25123270
TI - Caveolin-1 in oral squamous cell carcinoma microenvironment: an overview.
AB - Caveolin-1 plays an important role in the pathogenesis of oncogenic cell
transformation, tumorigenesis, and metastasis. Increased expression of caveolin-1
in an array of tumors has confirmed its value in prognosis. It has been
established that oxidative stress is the main cause for loss of stromal caveolin
1 via autophagy in the tumor microenvironment. In this overview, we attempt to
abridge the relationship between caveolin-1 and oral squamous cell carcinoma,
taking all the established theories into consideration.
PMID- 25123273
TI - Transcriptional and epigenetic networks orchestrating immune cell development and
function.
PMID- 25123274
TI - The role of chromatin dynamics in immune cell development.
AB - In immune cells, as in all mammalian cells, nuclear DNA is wrapped around
histones to form nucleosomes. The positioning and modifications of nucleosomes
throughout the genome defines the chromatin state of the cell and has a large
impact on gene regulation. Chromatin state is dynamic throughout immune cell
development and activation. High-throughput open chromatin assays, such as DNase
seq, can be used to find regulatory element across the genome and, when combined
with histone modifications, can specify their function. During hematopoiesis,
distal regulatory elements, known as enhancers, are established by pioneer
factors that alter chromatin state. Some of these enhancers are lost, some are
gained, and some are maintained as a memory of the cell's developmental origin.
The enhancer landscape is unique to the cell lineage-with different enhancers
regulating the same promoter-and determines the mechanism of cell type-specific
activation after exposure to stimuli. Histone modification and promoter
architecture govern the diverse responses to stimulation. Furthermore, chromatin
dynamics may explain the high plasticity of certain tissue-resident immune cell
types. Future epigenomic research will depend on the development of more
efficient experiments and better methods to associate enhancers with genes. The
ultimate goal of mapping genome-wide chromatin state throughout the hematopoietic
tree will help illuminate the mechanisms behind immune cell development and
function.
PMID- 25123276
TI - Deciphering the epigenetic code of T lymphocytes.
AB - The multiple lineages and differentiation states that constitute the T-cell
compartment all derive from a common thymic precursor. These distinct
transcriptional states are maintained both in time and after multiple rounds of
cell division by the concerted actions of a small set of lineage-defining
transcription factors that act in conjunction with a suite of chromatin-modifying
enzymes to activate, repress, and fine-tune gene expression. These chromatin
modifications collectively provide an epigenetic code that allows the stable and
heritable maintenance of the T-cell phenotype. Recently, it has become apparent
that the epigenetic code represents a therapeutic target for a variety of immune
cell disorders, including lymphoma and acute and chronic inflammatory diseases.
Here, we review the recent advances in epigenetic regulation of gene expression,
particularly as it relates to the T-cell differentiation and function.
PMID- 25123280
TI - Orchestration of plasma cell differentiation by Bach2 and its gene regulatory
network.
AB - Bach2 is a basic region-leucine zipper (bZip) transcription factor that forms
heterodimers with small Maf oncoproteins and binds to target genes, thus
repressing their expression. Bach2 is required for class switch recombination
(CSR) and somatic hypermutation (SHM) of immunoglobulin genes in activated B
cells. Bach2 represses the expression of Prdm1 encoding Blimp-1 repressor and
thereby inhibits terminal differentiation of B cells to plasma cells. This causes
a delay in the induction of Prdm1, thereby securing a time window for the
expression of Aicda encoding activation-induced cytidine deaminase (AID) required
for both CSR and SHM. Based on the characteristics of a gene regulatory network
(GRN) involving Bach2 and Prdm1 and its dynamics, a 'delay-driven diversity'
model was introduced to explain the responses of activated B cells. Bach2 is also
required for the proper differentiation and function of peripheral T cells. In
the absence of Bach2, CD4(+) T cells show increased differentiation to effector
cells producing higher levels of Th2-related cytokines, such as IL-4 and IL-10,
and a reduction in the generation of regulatory T cells. Bach2 represses many
genes in T cells, including Prdm1, suggesting that the Bach2-Prdm1 pathway is
also important in maintaining the homeostasis of T cells. Furthermore, Bach2 is
essential for the function of alveolar macrophages. Therefore, Bach2 orchestrates
both acquired and innate immunity at multiple points. Its connection with disease
is also reviewed in this report.
PMID- 25123279
TI - The regulatory network of B-cell differentiation: a focused view of early B-cell
factor 1 function.
AB - During the last decades, many studies have investigated the transcriptional and
epigenetic regulation of lineage decision in the hematopoietic system. These
efforts led to a model in which extrinsic signals and intrinsic cues establish a
permissive chromatin context upon which a regulatory network of transcription
factors and epigenetic modifiers act to guide the differentiation of
hematopoietic lineages. These networks include lineage-specific factors that
further modify the epigenetic landscape and promote the generation of specific
cell types. The process of B lymphopoiesis requires a set of transcription
factors, including Ikaros, PU.1, E2A, and FoxO1 to 'prime' cis-regulatory regions
for subsequent activation by the B-lineage-specific transcription factors EBF1
and Pax-5. The expression of EBF1 is initiated by the combined action of E2A and
FoxO1, and it is further enhanced and maintained by several positive feedback
loops that include Pax-5 and IL-7 signaling. EBF1 acts in concert with Ikaros,
PU.1, Runx1, E2A, FoxO1, and Pax-5 to establish the B cell-specific transcription
profile. EBF1 and Pax-5 also collaborate to repress alternative cell fates and
lock cells into the B-lineage fate. In addition to the functions of EBF1 in
establishing and maintaining B-cell identity, EBF1 is required to coordinate
differentiation with cell proliferation and survival.
PMID- 25123277
TI - Transcriptional and epigenetic regulation of T-helper lineage specification.
AB - Combined with TCR stimuli, extracellular cytokine signals initiate the
differentiation of naive CD4(+) T cells into specialized effector T-helper (Th)
and regulatory T (Treg) cell subsets. The lineage specification and commitment
process occurs through the combinatorial action of multiple transcription factors
(TFs) and epigenetic mechanisms that drive lineage-specific gene expression
programs. In this article, we review recent studies on the transcriptional and
epigenetic regulation of distinct Th cell lineages. Moreover, we review current
study linking immune disease-associated single-nucleotide polymorphisms with
distal regulatory elements and their potential role in the disease etiology.
PMID- 25123275
TI - Transcriptional and epigenetic networks of helper T and innate lymphoid cells.
AB - The discovery of the specification of CD4(+) helper T cells to discrete effector
'lineages' represented a watershed event in conceptualizing mechanisms of host
defense and immunoregulation. However, our appreciation for the actual complexity
of helper T-cell subsets continues unabated. Just as the Sami language of
Scandinavia has 1000 different words for reindeer, immunologists recognize the
range of fates available for a CD4(+) T cell is numerous and may be
underestimated. Added to the crowded scene for helper T-cell subsets is the
continuously growing family of innate lymphoid cells (ILCs), endowed with common
effector responses and the previously defined 'master regulators' for CD4(+)
helper T-cell subsets are also shared by ILC subsets. Within the context of this
extraordinary complexity are concomitant advances in the understanding of
transcriptomes and epigenomes. So what do terms like 'lineage commitment' and
helper T-cell 'specification' mean in the early 21st century? How do we put all
of this together in a coherent conceptual framework? It would be arrogant to
assume that we have a sophisticated enough understanding to seriously answer
these questions. Instead, we review the current status of the flexibility of
helper T-cell responses in relation to their genetic regulatory networks and
epigenetic landscapes. Recent data have provided major surprises as to what
master regulators can or cannot do, how they interact with other transcription
factors and impact global genome-wide changes, and how all these factors come
together to influence helper cell function.
PMID- 25123284
TI - Staying innate: transcription factor maintenance of innate lymphoid cell
identity.
AB - Innate and adaptive lymphocytes are characterized by phenotypic and functional
characteristics that result from genomic rearrangements (in the case of antigen
specific B and T cells) coupled with selective gene expression patterns that are
generated in a context-dependent fashion. Cell-intrinsic expression of
transcription factors (TFs) play a critical role in the regulation of gene
expression that establish the distinct lymphoid subsets but also have been
proposed to play an ongoing role in the maintenance of lineage-associated
transcriptional signatures that comprise lymphocyte identity. This is the case
for CD19(+) B cells that require Pax5 expression throughout their lifespan, as
well as for diverse T-helper subsets that have specialized immune functions.
Innate lymphoid cells (ILCs) comprise diverse effectors cells that differentiate
under TF control and have critical roles in the early stages of immune responses.
In this review, ILC development is reviewed and the requirement for persistent TF
expression in the maintenance of transcriptional signatures that define ILC
identity is explored.
PMID- 25123283
TI - The interface between transcriptional and epigenetic control of effector and
memory CD8+ T-cell differentiation.
AB - Immunity to many intracellular pathogens requires the proliferation,
differentiation, and function of CD8(+) cytotoxic T lymphocytes (CTLs). While the
majority of effector CTLs die upon clearance of the pathogen, a small proportion
of them survive to become long-lived memory CTLs. Memory CTLs can provide
protective immunity against re-exposure to the same pathogen and are the
principle motivation behind T-cell- based vaccine design. While a large body of
cellular immunologic research has proven invaluable to define effector and memory
CTLs by their different phenotypes and functions, an emerging focus in the field
has been to understand how environmental cues regulate CTL differentiation on a
genomic level. Genome-wide studies to profile transcriptional and epigenetic
changes during infection have revealed that dynamic changes in DNA methylation
patterns and histone modifications accompany transcriptional signatures that
define and regulate CTL differentiation states. In this review, we emphasize the
importance of epigenetic regulation of CD8(+) T-cell differentiation and the
likely role that transcription factors play in this process.
PMID- 25123278
TI - Innate immune regulation by STAT-mediated transcriptional mechanisms.
AB - The term innate immunity typically refers to a quick but non-specific host
defense response against invading pathogens. The innate immune system comprises
particular immune cell populations, epithelial barriers, and numerous secretory
mediators including cytokines, chemokines, and defense peptides. Innate immune
cells are also now recognized to play important contributing roles in cancer and
pathological inflammatory conditions. Innate immunity relies on rapid signal
transduction elicited upon pathogen recognition via pattern recognition receptors
(PRRs) and cell:cell communication conducted by soluble mediators, including
cytokines. A majority of cytokines involved in innate immune signaling use a
molecular cascade encompassing receptor-associated Jak protein tyrosine kinases
and STAT (signal transducer and activator of transcription) transcriptional
regulators. Here, we focus on roles for STAT proteins in three major innate
immune subsets: neutrophils, macrophages, and dendritic cells (DCs). While
knowledge in this area is only now emerging, understanding the molecular
regulation of these cell types is necessary for developing new approaches to
treat human disorders such as inflammatory conditions, autoimmunity, and cancer.
PMID- 25123281
TI - Mi-2/NuRD chromatin remodeling complexes regulate B and T-lymphocyte development
and function.
AB - Mi-2/nucleosomal remodeling and deacetylase (NuRD) complexes are important
epigenetic regulators of chromatin structure and gene expression. Mi-2/NuRD
complexes are an assemblage of proteins that combine key epigenetic regulators
necessary for (i) histone deacetylation and demethylation, (ii) binding to
methylated DNA, (iii) mobilization of nucleosomes, and (iv) recruitment of
additional regulatory proteins. Depending on their context in chromatin, Mi
2/NuRD complexes either activate or repress gene transcription. In this regard,
they are important regulators of hematopoiesis and lymphopoiesis. Mi-2/NuRD
complexes maintain pools of hematopoietic stem cells. Specifically, components of
these complexes control multiple stages of B-cell development by regulating B
cell specific transcription. With one set of components, they inhibit terminal
differentiation of germinal center B cells into plasma B cells. They also mediate
gene repression together with Blimp-1 during plasma cell differentiation. In
cooperation with Ikaros, Mi-2/NuRD complexes also play important roles in T-cell
development, including CD4 versus CD8 fate decisions and peripheral T-cell
responses. Dysregulation of NuRD during lymphopoiesis promotes leukemogenesis.
Here, we review general properties of Mi-2/NuRD complexes and focus on their
functions in gene regulation and development of lymphocytes.
PMID- 25123282
TI - Complex interactions of transcription factors in mediating cytokine biology in T
cells.
AB - T-helper (Th) cells play critical roles within the mammalian immune system, and
the differentiation of naive CD4(+) T cells into distinct T-helper subsets is
critical for normal immunoregulation and host defense. These carefully regulated
differentiation processes are controlled by networks of cytokines, transcription
factors, and epigenetic modifications, resulting in the generation of multiple
CD4(+) T-cell subsets, including Th1, Th2, Th9, Th17, Treg, and Tfh cells. In
this review, we discuss the roles of transcription factors in determining the
specific type of differentiation and in particular the role of interleukin-2 (IL
2) in promoting or inhibiting Th differentiation. In addition to discussing
master regulators and subset-specific transcription factors for distinct T-helper
cell populations, we focus on signal transducer and activator of transcription
(STAT) proteins and on the cooperative action of interferon regulatory factor 4
(IRF4) with activator protein 1 (AP-1) family proteins and STAT3 in the assembly
of complexes that broadly influence T-cell differentiation.
PMID- 25123286
TI - Carboxylated pillar[5]arene-coated gold nanoparticles with chemical stability and
enzyme-like activity.
AB - A facile synthesis of gold nanoparticles (AuNPs) covered with a multidentate
macrocycle, carboxylated pillar[5]arene (CP), via a one-pot hydrothermal process
is reported. The resulting AuNPs are highly stable against salts and pH
variations, while their traditional counterparts are not stable at the same
conditions. For the stabilization, multiple carboxylate groups of CP might
contribute to electrostatic or steric stabilization. In addition, we found that
CP-coated AuNPs exhibit greater peroxidase-like activity than citrate-stabilized
AuNPs in the presence of silver cations. The system presented herein would
provide a new scheme to fabricate unique sensory systems in combination with
enzymes, which can bind to the pocket of CP.
PMID- 25123287
TI - Polysaccharide-based oleogels prepared with an emulsion-templated approach.
AB - The preparation and characterization of oleogels structured by using a
combination of a surface-active and a non-surface-active polysaccharide through
an emulsion-templated approach is reported. Specifically, the oleogels were
prepared by first formulating a concentrated oil-in-water emulsion, stabilized
with a combination of cellulose derivatives and xanthan gum, followed by the
selective evaporation of the continuous water phase to drive the network
formation, resulting in an oleogel with a unique microstructure and interesting
rheological properties, including a high gel strength, G'>4000 Pa, shear
sensitivity, good thixotropic recovery, and good thermostability.
PMID- 25123290
TI - A search for the most accurate formula for sonographic weight estimation by fetal
sex - a retrospective cohort study.
AB - OBJECTIVE: The aim of this study was to assess the effect of fetal sex on the
accuracy of multiple formulas for sonographic estimation fetal weight (SEFW).
METHODS: The cohort included all singleton live births recorded at a single
medical center from January 2004 to September 2011. The accuracy of SEFW was
compared between male and female fetuses using 6575 SEFW performed within 3 days
prior to delivery. Fetal weight was estimated using 27 models. RESULTS: The
accuracy of different formulas in predicting birth weight of male and female
fetuses was found to be significantly different in almost every accuracy index
that was compared (P < 0.05). The model by Sabbagha et al. was found to be the
most accurate in assessing female fetuses. The most accurate model for male
fetuses was a sex-specific formula by Melamed et al. We also found that a
combination of the most accurate formula for each sex to one combined sex
specific model increased SEFW accuracy significantly. CONCLUSION: The accuracy of
SEFW is significantly related to fetal sex. The combination of the formulas by
Melamed et al. and Sabbagha et al. for male and female fetuses accordingly
allowed more accurate SEFW in our research population.
PMID- 25123289
TI - Metformin Restores Intermediate-Conductance Calcium-Activated K+ Channel- and
Small-Conductance Calcium-Activated K+ Channel-Mediated Vasodilatation Impaired
by Advanced Glycation End Products in Rat Mesenteric Artery. [Corrected].
AB - The present study was designed to investigate the effect of metformin on the
impairment of intermediate-conductance and small-conductance Ca(2+)-activated
potassium channels (IKCa and SKCa)-mediated relaxation in diabetes and the
underlying mechanism. The endothelial vasodilatation function of mesenteric
arteries was assessed with the use of wire myography. Expression levels of IKCa
and SKCa and phosphorylated Thr(172) of AMP-activated protein kinase (AMPK) were
measured using Western blot technology. The channel activity was observed using a
whole-cell patch voltage clamp. Reactive oxygen species (ROS) were measured using
dihydroethidium and 2',7'-dichlorofluorescein diacetate. Metformin restored the
impairment of IKCa- and SKCa-mediated vasodilatation in mesenteric arteries from
streptozotocin-induced type 2 diabetic rats and that from normal rats incubated
with advanced glycation end products (AGEs) for 3 hours. In cultured human
umbilical vein endothelial cells (HUVECs), 1 MUM metformin reversed AGE-induced
increase of ROS and attenuated AGE- and H2O2- induced downregulation of IKCa and
SKCa after long-term incubation (>24 hours). Short-term treatment (3 hours) with
1 MUM metformin reversed the decrease of IKCa and SKCa currents induced by AGE
incubation for 3 hours without changing the channel expression or the AMPK
activation in HUVECs. These results are the first to demonstrate that metformin
restored IKCa- and SKCa-mediated vasodilatation impaired by AGEs in rat
mesenteric artery, in which the upregulation of channel activity and protein
expression is likely involved.
PMID- 25123291
TI - On the photo-induced charge-carrier generation within monolayers of self
assembled organic donor-acceptor dyads.
AB - By means of STM and nc-AFM the self-assembly of a new donor-acceptor (DA) dyad
molecule on highly oriented pyrolytic graphite is identified and compared to
molecular simulations. Kelvin probe force microscopy (KPFM) measurements clearly
show the photovoltaic activity of this model system under illumination. The
optoelectronic properties and the local morphology of the DA dyad assembly are
simultaneously probed by KPFM down to the level of one molecular monolayers.
PMID- 25123292
TI - A facile synthesis of multi metal-doped rectangular ZnO nanocrystals using a
nanocrystalline metal-organic framework template.
AB - A multi metal (M: Fe, Co, and Ni)-doped rectangular ZnO nanocrystal (r-ZnO:M) was
synthesised using nanocrystalline metal-organic framework-5 (n-MOF-5). After
calcination in air, M-inserted n-MOF-5 led to r-ZnO:M of the wurtzite crystal
structure with a small amount (<1%) of spinel ZnM2O4 phase. The inserted metal
atoms of r-ZnO:M, replacing the Zn atoms of the wurtzite ZnO structure, were well
dispersed throughout the nanocrystal. Density functional theory calculations not
only confirm the structural stability of wurtzite r-ZnO:M and negligible
contribution of spinel ZnM2O4 but also elucidate the experimentally observed
increase of visible light absorbance and appearance of ferromagnetism upon metal
atom doping.
PMID- 25123288
TI - ABCD2 alters peroxisome proliferator-activated receptor alpha signaling in vitro,
but does not impair responses to fenofibrate therapy in a mouse model of diet
induced obesity.
AB - Fenofibrate is a peroxisome proliferator-activated receptor (PPAR) alpha ligand
that has been widely used as a lipid-lowering agent in the treatment of
hypertriglyceridemia. ABCD2 (D2) is a peroxisomal long-chain acyl-CoA transporter
that is highly induced by fenofibrate in the livers of mice. To determine whether
D2 is a modifier of fibrate responses, wild-type and D2-deficient mice were
treated with fenofibrate for 14 days. The absence of D2 altered expression of
gene clusters associated with lipid metabolism, including PPARalpha signaling.
Using 3T3-L1 adipocytes, which express high levels of D2, we confirmed that
knockdown of D2 modified genomic responses to fibrate treatment. We next
evaluated the impact of D2 on effects of fibrates in a mouse model of diet
induced obesity. Fenofibrate treatment opposed the development of obesity,
hypertriglyceridemia, and insulin resistance. However, these effects were
unaffected by D2 genotype. We concluded that D2 can modulate genomic responses to
fibrates, but that these effects are not sufficiently robust to alter the effects
of fibrates on diet-induced obesity phenotypes.
PMID- 25123285
TI - ID'ing innate and innate-like lymphoid cells.
AB - The immune system can be divided into innate and adaptive components that differ
in their rate and mode of cellular activation, with innate immune cells being the
first responders to invading pathogens. Recent advances in the identification and
characterization of innate lymphoid cells have revealed reiterative developmental
programs that result in cells with effector fates that parallel those of adaptive
lymphoid cells and are tailored to effectively eliminate a broad spectrum of
pathogenic challenges. However, activation of these cells can also be associated
with pathologies such as autoimmune disease. One major distinction between innate
and adaptive immune system cells is the constitutive expression of ID proteins in
the former and inducible expression in the latter. ID proteins function as
antagonists of the E protein transcription factors that play critical roles in
lymphoid specification as well as B- and T-lymphocyte development. In this
review, we examine the transcriptional mechanisms controlling the development of
innate lymphocytes, including natural killer cells and the recently identified
innate lymphoid cells (ILC1, ILC2, and ILC3), and innate-like lymphocytes,
including natural killer T cells, with an emphasis on the known requirements for
the ID proteins.
PMID- 25123293
TI - Water-stable zirconium-based metal-organic framework material with high-surface
area and gas-storage capacities.
AB - We designed, synthesized, and characterized a new Zr-based metal-organic
framework material, NU-1100, with a pore volume of 1.53 ccg(-1) and Brunauer
Emmett-Teller (BET) surface area of 4020 m(2) g(-1) ; to our knowledge, currently
the highest published for Zr-based MOFs. CH4 /CO2 /H2 adsorption isotherms were
obtained over a broad range of pressures and temperatures and are in excellent
agreement with the computational predictions. The total hydrogen adsorption at 65
bar and 77 K is 0.092 g g(-1) , which corresponds to 43 g L(-1) . The volumetric
and gravimetric methane-storage capacities at 65 bar and 298 K are approximately
180 vSTP /v and 0.27 g g(-1) , respectively.
PMID- 25123294
TI - Lasting personality pathology following exposure to catastrophic trauma in
adults: systematic review.
AB - BACKGROUND: By definition, personality disorders (PDs) are evident in late
childhood and adolescence, but evidence for personality pathology occurring after
adolescence is unclear. AIM: We aimed to review extant literature on personality
change following exposure to catastrophic trauma in adults in order to identify
the prevalence and clinical features of any long-term personality pathology.
METHOD: Relevant studies were identified by searching three bibliographic
databases (MEDLINE, EMBASE and PsychINFO) from inception to November 2011 using
terms related to personality and trauma. RESULTS: No prospective studies that
investigated long-term personality change following exposure to trauma in adults
were found. Two retrospective studies reported the prevalence of enduring
personality change of 2.6% and 6% (weighted prevalence 4.6%, 95% confidence
interval 3.4-6.3%), and one study reported 20% increase in adult-onset antisocial
behaviour following exposure to trauma. Findings from cross-sectional studies
that examined the prevalence of PDs in people exposed to catastrophic trauma
reported that Cluster C and Cluster A were the most common with avoidant,
paranoid and obsessive-compulsive PDs among those most frequently reported.
CONCLUSION: A minority of adults who are exposed to severe trauma appear to go on
to develop significant personality pathology. The observed personality
disturbance is multifarious and more extensive than the prototype described in
ICD-10.
PMID- 25123296
TI - Maximum likelihood estimation of FRET efficiency and its implications for
distortions in pixelwise calculation of FRET in microscopy.
AB - Ratiometric determination of the efficiency of fluorescence or Forster resonance
energy transfer (FRET) is one of the most widespread methods for the
characterization of protein clustering and conformation. Low photon numbers,
often present in pixel-by-pixel determination of FRET efficiency in digital
microscopy, result in large uncertainties in the derived FRET parameter. Here, we
propose a method based on maximum likelihood estimation (MLE) of FRET efficiency
using photon counting detectors to overcome this limitation. Intensities measured
in the donor, FRET, and acceptor channels were all assumed to follow Poisson
statistics as a result of detector shot noise. The joint probability of photon
numbers detected in the donor, FRET, and acceptor channels was derived using an
equation describing the relationship between the three measured intensities. The
FRET efficiency generating the measured photon numbers with the largest
likelihood was determined iteratively providing a single FRET value for all
pixels in the calculation. Since as few as 100 pixels are sufficient to provide a
maximum likelihood estimate for FRET, biological variability in FRET values can
be revealed by performing the analysis for regions of interests in an image.
Since the algorithm provides the probability of a combination of donor, FRET, and
acceptor intensities observed in each individual pixel given a certain FRET
efficiency, outlier pixels with low probabilities could be excluded from the
analysis. Simulations carried out with low photon numbers in the presence and
absence of outlier pixels revealed that the proposed approach can reliably and
reproducibly estimate FRET efficiency. In addition, systematic evaluation of the
simulation results showed that the distribution of pixel-by-pixel FRET
efficiencies is skewed, and the mean of these FRET values is a biased and
unreliable estimate of the FRET efficiency. In the absence of outlier pixels,
FRET calculated from summed donor, FRET, and acceptor intensities proved to be as
reliable as MLE. We conclude that MLE of FRET outperforms calculations using
summed and pixel-by-pixel intensities in biologically relevant situations
involving low photon numbers and outlier pixels. (c) 2014 International Society
for Advancement of Cytometry.
PMID- 25123295
TI - A multicentre randomized trial of the treatment of patients with pemphigus
vulgaris with infliximab and prednisone compared with prednisone alone.
AB - BACKGROUND: Pemphigus vulgaris (PV) is a blistering disease and tumour necrosis
factor-alpha has a role in its pathogenesis. OBJECTIVES: To evaluate the safety
of infliximab (IFX) with prednisone compared with prednisone alone in the
treatment of PV. In addition, treatment response was assessed and mechanistic
studies were performed. METHODS: Subjects with PV who had ongoing disease
activity while being maintained on prednisone were randomized to receive either
IFX or placebo in addition to prednisone. Response status and immunoglobulin (Ig)
G anti-desmoglein (Dsg)1 and Dsg3 antibodies were assessed at 18 and 26 weeks.
RESULTS: Ten subjects were randomized to each group. There were no safety signals
during the course of the study. At week 18, one subject in each group had
responded. At week 26, three IFX-treated subjects vs. none in the placebo group
had responded (P = 0.21). At weeks 18 and 26, the median IgG anti-Dsg1 and anti
Dsg3 levels were lower in the IFX-treated patients [IgG anti-Dsg-1 (week 18, P =
0.035; week 26, P = 0.022); IgG anti-Dsg3 (week 18, P = 0.035; week, 26 P =
0.05)]. CONCLUSIONS: This study is limited by the relatively small sample size.
There was no significant difference between study arms in the proportion of
subjects with treatment-related adverse events > grade 3. IFX therapy was not
shown to be effective for the treatment of patients with PV in this randomized,
placebo-controlled trial, although IFX treatment may be associated with a
decrease in anti-Dsg1 and Dsg3 antibodies.
PMID- 25123298
TI - Patient-reported outcomes of dental implant therapy in a large randomly selected
sample.
AB - BACKGROUND: In addition to traditional clinical parameters, the need to include
patient-reported assessments into dental implant research has been emphasized.
AIM: The aim of this study was to evaluate patient-reported outcomes following
implant-supported restorative therapy in a randomly selected patient sample.
MATERIAL AND METHODS: Four thousand seven hundred and sixteen patients were
randomly selected from the data register of the Swedish Social Insurance Agency.
A questionnaire containing 10 questions related to implant-supported restorative
therapy was mailed to each of the individuals about 6 years after therapy.
Associations between questionnaire data, and (i) patient-related, (ii) clinician
related and (iii) therapy-related variables were identified by multivariate
analyses. RESULTS: Three thousand eight hundred and twenty-seven patients (81%)
responded to the questionnaire. It was demonstrated that the overall satisfaction
among patients was high. Older patients presented with an overall more positive
perception of the results of the therapy than younger patients and males were
more frequently satisfied in terms of esthetics than females. While clinical
setting did not influence results, patients treated by specialist dentists as
opposed to general practitioners reported a higher frequency of esthetic
satisfaction and improved chewing ability. In addition, patients who had received
extensive implant-supported reconstructions, in contrast to those with small
reconstructive units, reported more frequently on improved chewing ability and
self-confidence but also to a larger extent on implant-related complications.
CONCLUSION: It is suggested that patient-perceived outcomes of implant-supported
restorative therapy are related to (i) age and gender of the patient, (ii) the
extent of restorative therapy and (iii) the clinician performing the treatment.
PMID- 25123303
TI - Building up a chemical proteomics network in Europe and beyond.
PMID- 25123297
TI - Tumor genome analysis includes germline genome: are we ready for surprises?
AB - We sought to describe the spectrum of potential and confirmed germline genomic
events incidentally identified during routine medium-throughput somatic tumor DNA
sequencing, and to provide a framework for pre- and post-test consent and
counseling for patients and families. Targeted tumor-only next-generation
sequencing (NGS) had been used to evaluate for possible druggable genomic events
obtained from consecutive new patients with metastatic gastroesophageal,
hepatobiliary or colorectal cancer seen at the University of Chicago. A panel of
medical oncologists, cancer geneticists and genetic counselors retrospectively
grouped these patients (N = 111) based on probability of possessing a potentially
inherited mutation in a cancer susceptibility gene, both prior to and after
incorporating tumor-only NGS results. High-risk patients (determined from NGS
results) were contacted and counseled in person by a genetic counselor (N = 21).
When possible and indicated, germline genetic testing was offered. Of 8 evaluable
high-risk patients, 7 underwent germline testing. Three (37.5%) had confirmed
actionable germline mutations (all in the BRCA2 gene). NGS offers promise, but
poses significant challenges for oncologists who are ill prepared to handle
incidental findings that have clinical implications for at risk family members.
In this relatively small cohort of patients undergoing tumor genomic testing for
gastrointestinal malignancies, we incidentally identified 3 BRCA2 mutations
carriers. This report underscores the need for oncologists to develop a framework
for pre- and post-test communication of risks to patients undergoing routine
tumor-only sequencing.
PMID- 25123302
TI - Carlos F. Barbas III (1964-2014): Visionary at the interface of chemistry and
biology.
PMID- 25123304
TI - Report from the Third Annual Symposium of the RIKEN-Max Planck Joint Research
Center for Systems Chemical Biology.
AB - The third Annual Symposium of the RIKEN-Max Planck Joint Research Center for
Systems Chemical Biology was held at Ringberg castle, May 21-24, 2014. At this
meeting 45 scientists from Japan and Germany presented the latest results from
their research spanning a broad range of topics in chemical biology and
glycobiology.
PMID- 25123305
TI - The pathology of bowel cancer screening.
AB - Colorectal cancer screening is widely promulgated in many parts of the world and
population screening is occurring in many countries, especially in western
Europe. Although, intuitively, it might be thought that the pathology resulting
from screening should be straightforward, being mainly that of polyp diagnosis
and the biopsy diagnosis and staging of established adenocarcinoma, in fact
experience has shown that there are several areas of considerable difficulty and
controversy. In the UK somewhat different programmes, all based on faecal occult
blood (FOB) screening, have been developed and each has generated similar
pathological conundra. These include the biopsy diagnosis of adenocarcinoma,
colorectal serrated pathology, the diagnosis and management of polyp cancers and
last, but certainly not least, the phenomenon of the large sigmoid colonic
adenomatous polyp with epithelial misplacement/pseudo-invasion. Polyp cancers
provide especially difficult management conundra and discussion of that
management within a multidisciplinary team-based management meeting is regarded
as essential in the UK. Large adenomatous polyps of the sigmoid colon with
epithelial misplacement are selected into FOB-based screening programmes and have
provided extraordinary diagnostic challenges. Finally, the quality assurance
procedures introduced for screening can ensure a considerable overall improvement
in the quality of lower gastrointestinal tract pathological reporting.
PMID- 25123306
TI - Effects of cortical microstimulation on confidence in a perceptual decision.
AB - Decisions are often associated with a degree of certainty, or confidence--an
estimate of the probability that the chosen option will be correct. Recent
neurophysiological results suggest that the central processing of evidence
leading to a perceptual decision also establishes a level of confidence. Here we
provide a causal test of this hypothesis by electrically stimulating areas of the
visual cortex involved in motion perception. Monkeys discriminated the direction
of motion in a noisy display and were sometimes allowed to opt out of the
direction choice if their confidence was low. Microstimulation did not reduce
overall confidence in the decision but instead altered confidence in a manner
that mimicked a change in visual motion, plus a small increase in sensory noise.
The results suggest that the same sensory neural signals support choice, reaction
time, and confidence in a decision and that artificial manipulation of these
signals preserves the quantitative relationship between accumulated evidence and
confidence.
PMID- 25123308
TI - Separate microcircuit modules of distinct v2a interneurons and motoneurons
control the speed of locomotion.
AB - Spinal circuits generate locomotion with variable speed as circumstances demand.
These circuits have been assumed to convey equal and uniform excitation to all
motoneurons whose input resistance dictates their activation sequence. However,
the precise connectivity pattern between excitatory premotor circuits and the
different motoneuron types has remained unclear. Here, we generate a connectivity
map in adult zebrafish between the V2a excitatory interneurons and slow,
intermediate, and fast motoneurons. We show that the locomotor network does not
consist of a uniform circuit as previously assumed. Instead, it can be
deconstructed into three separate microcircuit modules with distinct V2a
interneuron subclasses driving slow, intermediate, or fast motoneurons. This
modular design enables the increase of locomotor speed by sequentially adding
microcircuit layers from slow to intermediate and fast. Thus, this principle of
organization of vertebrate spinal circuits represents an intrinsic mechanism to
increase the locomotor speed by incrementally engaging different motor units.
PMID- 25123307
TI - The crystal structure of netrin-1 in complex with DCC reveals the bifunctionality
of netrin-1 as a guidance cue.
AB - Netrin-1 is a guidance cue that can trigger either attraction or repulsion
effects on migrating axons of neurons, depending on the repertoire of receptors
available on the growth cone. How a single chemotropic molecule can act in such
contradictory ways has long been a puzzle at the molecular level. Here we present
the crystal structure of netrin-1 in complex with the Deleted in Colorectal
Cancer (DCC) receptor. We show that one netrin-1 molecule can simultaneously bind
to two DCC molecules through a DCC-specific site and through a unique generic
receptor binding site, where sulfate ions staple together positively charged
patches on both DCC and netrin-1. Furthermore, we demonstrate that UNC5A can
replace DCC on the generic receptor binding site to switch the response from
attraction to repulsion. We propose that the modularity of binding allows for the
association of other netrin receptors at the generic binding site, eliciting
alternative turning responses.
PMID- 25123309
TI - Amygdala-dependent fear memory consolidation via miR-34a and Notch signaling.
AB - Using an array-based approach after auditory fear conditioning and microRNA
(miRNA) sponge-mediated inhibition, we identified a role for miR-34a within the
basolateral amygdala (BLA) in fear memory consolidation. Luciferase assays and
bioinformatics suggested the Notch pathway as a target of miR-34a. mRNA and
protein levels of Notch receptors and ligands are downregulated in a time- and
learning-specific manner after fear conditioning in the amygdala. Systemic and
stereotaxic manipulations of the Notch pathway indicated that Notch signaling in
the BLA suppresses fear memory consolidation. Impairment of fear memory
consolidation after inhibition of miR-34a within the BLA is rescued by inhibiting
Notch signaling. Together, these data suggest that within the BLA, a transient
decrease in Notch signaling, via miR-34a regulation, is important for the
consolidation of fear memory. This work expands the idea that developmental
molecules have roles in adult behavior and that existing interventions targeting
them hold promise for treating neuropsychiatric disorders. VIDEO ABSTRACT:
PMID- 25123310
TI - Long-distance axonal growth from human induced pluripotent stem cells after
spinal cord injury.
AB - Human induced pluripotent stem cells (iPSCs) from a healthy 86-year-old male were
differentiated into neural stem cells and grafted into adult immunodeficient rats
after spinal cord injury. Three months after C5 lateral hemisections, iPSCs
survived and differentiated into neurons and glia and extended tens of thousands
of axons from the lesion site over virtually the entire length of the rat CNS.
These iPSC-derived axons extended through adult white matter of the injured
spinal cord, frequently penetrating gray matter and forming synapses with rat
neurons. In turn, host supraspinal motor axons penetrated human iPSC grafts and
formed synapses. These findings indicate that intrinsic neuronal mechanisms
readily overcome the inhibitory milieu of the adult injured spinal cord to extend
many axons over very long distances; these capabilities persist even in neurons
reprogrammed from very aged human cells. VIDEO ABSTRACT:
PMID- 25123311
TI - Network structure within the cerebellar input layer enables lossless sparse
encoding.
AB - The synaptic connectivity within neuronal networks is thought to determine the
information processing they perform, yet network structure-function relationships
remain poorly understood. By combining quantitative anatomy of the cerebellar
input layer and information theoretic analysis of network models, we investigated
how synaptic connectivity affects information transmission and processing.
Simplified binary models revealed that the synaptic connectivity within
feedforward networks determines the trade-off between information transmission
and sparse encoding. Networks with few synaptic connections per neuron and
network-activity-dependent threshold were optimal for lossless sparse encoding
over the widest range of input activities. Biologically detailed spiking network
models with experimentally constrained synaptic conductances and inhibition
confirmed our analytical predictions. Our results establish that the synaptic
connectivity within the cerebellar input layer enables efficient lossless sparse
encoding. Moreover, they provide a functional explanation for why granule cells
have approximately four dendrites, a feature that has been evolutionarily
conserved since the appearance of fish.
PMID- 25123313
TI - Unique interweaved microtubule scaffold mediates osmosensory transduction via
physical interaction with TRPV1.
AB - The electrical activity of mammalian osmosensory neurons (ONs) is increased by
plasma hypertonicity to command thirst, antidiuretic hormone release, and
increased sympathetic tone during dehydration. Osmosensory transduction is a
mechanical process whereby decreases in cell volume cause the activation of
transient receptor potential vanilloid type-1 (TRPV1) channels to induce
depolarization and increase spiking activity in ONs. However, it is not known how
cell shrinking is mechanically coupled to channel activation. Using
superresolution imaging, we found that ONs are endowed with a uniquely
interweaved scaffold of microtubules throughout their somata. Microtubules
physically interact with the C terminus of TRPV1 at the cell surface and provide
a pushing force that drives channels activation during shrinking. Moreover, we
found that changes in the density of these interactions can bidirectionally
modulate osmosensory gain. Microtubules are thus an essential component of the
vital neuronal mechanotransduction apparatus that allows the brain to monitor and
correct body hydration.
PMID- 25123312
TI - Dnmt3a regulates global gene expression in olfactory sensory neurons and enables
odorant-induced transcription.
AB - During differentiation, neurons exhibit a reorganization of DNA modification
patterns across their genomes. The de novo DNA methyltransferase Dnmt3a is
implicated in this process, but the effects of its absence have not been fully
characterized in a purified neuronal population. To better understand how DNA
modifications contribute to neuronal function, we performed a comprehensive
analysis of the epigenetic and transcriptional landscapes of Dnmt3a-deficient
mature olfactory sensory neurons (mOSNs), the primary sensory neurons of the
olfactory epithelium. Dnmt3a is required for both 5-methylcytosine and 5
hydroxymethylcytosine patterning within accessible genomic regions, including
hundreds of neurodevelopmental genes and neural enhancers. Loss of Dnmt3a results
in the global disruption of gene expression via activation of silent genes and
reduction of mOSN-expressed transcripts. Importantly, the DNA modification state
and inducibility of odorant-activated genes are markedly impaired in Dnmt3a
knockouts, suggesting a crucial role for this enzyme in establishing an
epigenetic landscape compatible with neuronal plasticity.
PMID- 25123315
TI - [Pulmonary hypertension in internal medicine].
PMID- 25123316
TI - [Intervention research in public health. Methodological and legal aspects of
collective interventions].
PMID- 25123314
TI - The Drosophila IR20a clade of ionotropic receptors are candidate taste and
pheromone receptors.
AB - Insects use taste to evaluate food, hosts, and mates. Drosophila has many
"orphan" taste neurons that express no known taste receptors. The Ionotropic
Receptor (IR) superfamily is best known for its role in olfaction, but virtually
nothing is known about a clade of ~35 members, the IR20a clade. Here, a
comprehensive analysis of this clade reveals expression in all taste organs of
the fly. Some members are expressed in orphan taste neurons, whereas others are
coexpressed with bitter- or sugar-sensing Gustatory receptor (Gr) genes. Analysis
of the closely related IR52c and IR52d genes reveals signatures of adaptive
evolution, roles in male mating behavior, and sexually dimorphic expression in
neurons of the male foreleg, which contacts females during courtship. These
neurons are activated by conspecific females and contact a neural circuit for
sexual behavior. Together, these results greatly expand the repertoire of
candidate taste and pheromone receptors in the fly.
PMID- 25123317
TI - [Pulmonary hypertension in chronic respiratory diseases].
AB - Pulmonary hypertension is frequent in advanced chronic respiratory diseases, with
an estimated prevalence at the time of pulmonary transplantation of 30-50 % in
idiopathic pulmonary fibrosis, 30-50 % in chronic obstructive pulmonary disease,
50 % in combined pulmonary fibrosis and emphysema, 75 % in sarcoidosis, and more
than 75 % of cases in pulmonary Langerhans cell histiocytosis. Histologic
features include varying degrees of pulmonary arterial remodeling (prominent),
vascular rarefaction (emphysema), fibrosis or specific involvement of the
pulmonary arteries (idiopathic pulmonary fibrosis, sarcoidosis,
lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis), in situ
thrombosis, and frequently associated involvement of the pulmonary veins
(idiopathic pulmonary fibrosis, sarcoidosis). Pulmonary hypertension is usually
detected using echocardiography with Doppler, however right heart catheterisation
is required to confirm precapillary pulmonary hypertension defined by pulmonary
artery pressure >= 25 mm Hg, with pulmonary artery wedge pressure <= 15 mm Hg.
When present, it is associated with decreased exercise capacity and worse
mortality. Pulmonary hypertension in chronic respiratory disease is almost
invariably multifactorial; hypoxia is one of its main determinants, however
supplemental oxygen therapy rarely reverses pulmonary hypertension. Management of
pulmonary hypertension in chronic respiratory disease is mostly based on the
optimal treatment of the underlying disease. Available data do not support the
use of drug therapies specific for pulmonary hypertension in the setting of
chronic respiratory diseases, however very few clinical studies have been
conducted so far specifically in this context.
PMID- 25123318
TI - Increasing occurrence of choledochal malformations in children: a single-center
37-year experience from Finland.
AB - OBJECTIVE: Few reports on choledochal malformations (CMs) in European populations
exist. MATERIALS AND METHODS: The medical records of pediatric CM patients
managed in our nationwide referral center for pediatric hepatobiliary surgery
between 1976 and 2013 (n = 38; 71% females) were reviewed. RESULTS: Over follow
up time, the relative proportion of fusiform CMs increased significantly (p =
0.007) and the estimated total incidence rose from 1:128,000 to 1:38,000 (p =
0.017). Cystic CMs (42%) presented at younger age than fusiform CMs (47%) (0.8
vs. 4.6 years, p = 0.001). Two-thirds had abdominal pain and half were
cholestatic at presentation. Pancreatitis had occurred in 16%. In addition to
ultrasound, 71% underwent magnetic resonance cholangiopancreatography and 39%
underwent endoscopic retrograde cholangiopancreatography. Median CM dilatation
was 15 (10-28) mm and a 12 (9-13) mm long common pancreaticobiliary channel was
confirmed in 61%, increasingly during recent years. Intrahepatic biliary tree was
dilated in 19%, whereas main ducts were dilated in 50%. Apart from two operated
in the 1970s and one with choledochocele, patients underwent resection of
extrahepatic bile ducts with Roux-en-Y hepaticojejunostomy at age of 4.2 (0.8
9.2) years. Postoperative bile leakage and hemorrhage required reoperations in
two. At last follow-up 4.8 (1.3-13.2) years postoperatively, none had dilated
intrahepatic biliary ducts or elevated plasma bilirubin (5 [3-7] umol/l). Single
cholangitis episodes had occurred in two, whereas others were asymptomatic.
CONCLUSION: CM incidence has increased significantly in Finland, being currently
over threefold higher than previous estimates in the Western world would suggest.
Removal of the extrahepatic biliary tree with hepaticojejunostomy for type I and
IV CMs yielded excellent results.
PMID- 25123320
TI - Narrowing the cystoscopy gap.
PMID- 25123319
TI - Kinetic and stoichiometric characterization of organoautotrophic growth of
Ralstonia eutropha on formic acid in fed-batch and continuous cultures.
AB - Formic acid, acting as both carbon and energy source, is a safe alternative to a
carbon dioxide, hydrogen and dioxygen mix for studying the conversion of carbon
through the Calvin-Benson-Bassham (CBB) cycle into value-added chemical compounds
by non-photosynthetic microorganisms. In this work, organoautotrophic growth of
Ralstonia eutropha on formic acid was studied using an approach combining
stoichiometric modeling and controlled cultures in bioreactors. A strain deleted
of its polyhydroxyalkanoate production pathway was used in order to carry out a
physiological characterization. The maximal growth yield was determined at 0.16
Cmole Cmole(-1) in a formate-limited continuous culture. The measured yield
corresponded to 76% to 85% of the theoretical yield (later confirmed in pH
controlled fed-batch cultures). The stoichiometric study highlighted the
imbalance between carbon and energy provided by formic acid and explained the low
growth yields measured. Fed-batch cultures were also used to determine the
maximum specific growth rate (MUmax = 0.18 h(-1) ) and to study the impact of
increasing formic acid concentrations on growth yields. High formic acid
sensitivity was found in R eutropha since a linear decrease in the biomass yield
with increasing residual formic acid concentrations was observed between 0 and
1.5 g l(-1) .
PMID- 25123321
TI - Harnessing big data for health care and research: are urologists ready?
AB - We are at a crossroads in terms of the data we collect and how they are analyzed.
In health care, big data analytics may uncover associations, patterns, and trends
with the potential to advance patient care and lower costs. To adapt to this
approach, urologists will have to ask the right questions.
PMID- 25123322
TI - Robotics: Will they give a new kick to single-site surgery?
PMID- 25123323
TI - The development of prognostic and predictive biomarkers in renal cell cancer are
not one and the same thing.
PMID- 25123324
TI - Editorial.
PMID- 25123326
TI - Increasing the sensitivity of endocervical curettings by performing ThinPrep(r)
Pap on transport container fluid: is diagnostic material going down the drain?
AB - OBJECTIVE: The sensitivity of endocervical curettage (ECC) can be suboptimal
because of limited epithelial tissue. The false-negative rate for ECC in patients
with cervical intraepithelial neoplasia involving the endocervical canal has been
reported to be 45%. ECC samples are transported to pathology in formalin- or
saline-filled containers; this fluid is discarded after the specimen has been
submitted. We evaluated the utility of performing liquid-based cytological
preparations from ECC transport container fluid as a way to increase the
sensitivity of ECC specimens. METHODS: Consecutive ECC specimens received at one
of the two participating institutions were selected prospectively. A surgical
pathology mesh bag was placed over a ThinPrep((r)) CytoLyt((r)) solution
container, and the specimen was filtered through the bag, collecting the
transport fluid in the container. The CytoLyt((r)) was processed to obtain a
container fluid ThinPrep((r)) (CF-TP) liquid-based Papanicolaou (Pap) slide. The
CF-TP slides were reviewed and the findings were compared with those from the ECC
and follow-up specimens. RESULTS: The cohort included 53 patients. Discrepancies
between CF-TP and ECC were seen in 14 of the 53 patients (26%); a more
significant lesion was identified in CF-TP relative to ECC in 13 of these cases.
CF-TP diagnosis was confirmed in eight of 11 cases with histological follow-up. A
positive CF-TP result was confirmed by histology in six of nine cases with
negative ECC. CONCLUSIONS: Combining the pathological evaluation of ECC specimens
with liquid-based cytology performed on the transport container fluid can
increase the diagnostic sensitivity of the ECC procedure for the detection of
cervical lesions.
PMID- 25123327
TI - Investigations on a wheat bran biorefinery involving organosolv fractionation and
enzymatic treatment.
AB - The present study elucidates the organosolv treatment of wheat bran, the major by
product of the milling industry. The influence of temperature (160-200 degrees C)
and ethanol concentration (30-60% (w/w)) at a given process time of 30min was
investigated. Enzymatic treatments of the organosolv extracts including solid
residues led to an overall glucose yield of 75%. The conversion of hemicelluloses
into xylose and arabinose was approximately 60% and 45%, respectively. Proteins
could be almost completely dissolved, however, practically no free amino acids
were obtained. Surprisingly, only around 30% of lignin and 65% of minerals were
dissolved. Severe treatment conditions induced the disintegration of fat into
glycerol and fatty acids as well as the formation of sugar degradation products.
During the lignin precipitation step, proteins partially coprecipitated.
PMID- 25123329
TI - Normovolemic hemodilution using hydroxyethyl starch 130/0.4 (Voluven) in a
Jehovah's Witness child requiring cardiopulmonary bypass for ventricular septal
defect repair.
AB - Surgical repair of congenital heart disease during cardiopulmonary bypass is
common, and performing these complicated procedures in the absence of blood
transfusions is especially challenging. A case of a Jehovah's Witness child who
underwent surgical repair of a ventricular septal defect utilizing a new
tetrastarch for autologous normovolemic hemodilution is reported. A successful
operative repair was achieved without the need for non-autologous blood
transfusion.
PMID- 25123328
TI - Speeded manual responses to unseen visual stimuli in hemianopic patients: what
kind of blindsight?
AB - Blindsight, i.e., unconscious visually guided behaviour triggered by stimuli
presented to a cortically blind hemifield, has been typically found either by
using direct (forced choice) or indirect (interhemispheric) methods. However, one
would expect to find blindsight also in fast responses to suddenly appearing
visual stimuli, a reminiscence of evolutionary ancient adaptive behaviour. In
this study we provide preliminary evidence of this form of blindsight by using a
conservative method for assessing blindsight based on a comparison between the
cumulative probability functions (CPFs) of simple reaction times to blind and
intact field stimuli. Furthermore, in two patients with blindsight we provided
evidence that their above-chance unconscious responses were likely to be
triggered by the intact hemisphere.
PMID- 25123330
TI - Outbreak of variant hand-foot-and-mouth disease caused by coxsackievirus A6 in
Auckland, New Zealand.
AB - Hand-foot-and-mouth disease is a common, usually mild childhood illness caused by
enteroviruses. Over the last five years, coxsackievirus A6 has been identified as
a causative agent in outbreaks in Europe, South-East Asia and America. It has an
atypical presentation compared with other enteroviruses, with more widespread
rash, larger blisters and subsequent skin peeling and/or nail shedding. We give
the first description of an outbreak of coxsackievirus A6 in New Zealand and how
health-care communication networks enabled detection of and dissemination of
information about this emergent strain.
PMID- 25123331
TI - Frequency of thrombotic risk factors in Chinese familial Budd-Chiari Syndrome.
PMID- 25123332
TI - Serum soluble CD40 Ligand levels are associated with severity and mortality of
brain trauma injury patients.
AB - BACKGROUND: Serum soluble CD40 Ligand (sCD40L) levels, which exhibit
prothrombotic and proinflammatory properties, have not been studied in patients
with traumatic brain injury (TBI). Thus, the objective of this study was to
determine whether serum sCD40L levels are associated with severity and mortality
in patients with severe TBI. METHODS: This was a prospective, observational and
multicenter study carried out in six Spanish Intensive Care Units. Patients with
severe TBI defined as Glasgow Coma Scale (GCS) lower than 9 were included, while
those with Injury Severity Score (ISS) in non-cranial aspects higher than 9 were
excluded. Serum levels of sCD40L were measured on the day of TBI. Endpoint was
established in 30-day mortality. RESULTS: We found higher serum sCD40L levels
(P<0.001) in non-surviving TBI patients (N=27) than in survivor ones (N=73).
Logistic regression analysis showed that serum sCD40L levels were associated with
30-day mortality (OR=1.58; 95% CI=1.12-2.21; P=0.008) controlling for APACHE-II
score and computer tomography findings. The area under the curve (AUC) for serum
sCD40L levels as predictor of 30-day mortality was 0.79 (95% CI=0.70-0.86;
P<0.001). Survival analysis showed that patients with serum sCD40L levels higher
than 2.11 ng/mL presented increased 30-day mortality than patients with lower
levels (Hazard ratio=9.0; 95% CI=4.25-19.27; P<0.001). We found an association
between serum sCD40L levels and APACHE-II (rho=0.33; P=0.001), and GCS score
(rho=-0.21; P=0.04). CONCLUSIONS: To our knowledge, this is the first study
reporting data on serum sCD40L levels in patients with severe TBI. The most
relevant and newer findings of our study are that serum sCD40L levels in non
surviving patients with severe TBI are higher than in surviving ones, and that
there are an association between serum sCD40L levels and TBI severity and
mortality.
PMID- 25123334
TI - High exposure to erlotinib and severe drug-induced interstitial lung disease in
patients with non-small-cell lung cancer.
PMID- 25123333
TI - Interval lung cancers not detected on screening chest X-rays: How are they
different?
AB - BACKGROUND: The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial
provides us an opportunity to describe interval lung cancers not detected by
screening chest X-ray (CXR) compared to screen-detected cancers. METHODS:
Participants were screened for lung cancer with CXR at baseline and annually for
two (never smokers) or three (ever smokers) more years. Screen-detected cancers
were those with a positive CXR and diagnosed within 12 months. Putative interval
cancers were those with a negative CXR screen but with a diagnosis of lung cancer
within 12 months. Potential interval cancers were re-reviewed to determine
whether lung cancer was missed and probably present during the initial
interpretation or whether the lesion was a "true interval" cancer. RESULTS:
77,445 participants were randomized to the intervention arm with 70,633 screened.
Of 5227 positive screens from any screening round, 299 resulted in screen
detected lung cancers; 151 had potential interval cancers with 127 CXR available
for re-review. Cancer was probably present in 45/127 (35.4%) at time of
screening; 82 (64.6%) were "true interval" cancers. Compared to screen-detected
cancers, true interval cancers were more common among males, persons with <12
years education and those with a history of smoking. True interval lung cancers
were more often small cell, 28.1% vs. 7.4%, and less often adenocarcinoma, 25.6%
vs. 56.2% (p<0.001), more advanced stage IV (30.5% vs. 16.6%, p<0.02), and less
likely to be in the right upper lobe, 17.1% vs. 36.1% (p<0.02). CONCLUSION: True
interval lung cancers differ from CXR-screen-detected cancers with regard to
demographic variables, stage, cell type and location. ClinicalTrials.gov number:
NCT00002540.
PMID- 25123335
TI - [Pushing the boundaries: How stereotactic irradiation offers new hope for
treatment].
PMID- 25123337
TI - Metabolic syndrome and peripheral arterial disease.
PMID- 25123336
TI - Analysis in conditional cannabinoid 1 receptor-knockout mice reveals neuronal
subpopulation-specific effects on epileptogenesis in the kindling paradigm.
AB - The endocannabinoid system serves as a retrograde negative feedback mechanism. It
is thought to control neuronal activity in an epileptic neuronal network. The
purpose of this study was to evaluate the impact of the endocannabinoid and
endovanilloid systems on both epileptogenesis and ictogenesis. Therefore, we
modulated the endocannabinoid and endovanilloid systems genetically and
pharmacologically, and analyzed the subsequent impact on seizure progression in
the kindling model of temporal lobe epilepsy in mice. In addition, the impact of
seizures on associated cellular alterations was evaluated. Our principal results
revealed that the endocannabinoid system affects seizure and afterdischarge
duration dependent on the neuronal subpopulation being modulated. Genetic
deletion of CB1-receptors (CB1Rs) from principal neurons of the forebrain and
pharmacological antagonism with rimonabant (5 mg/kg) caused longer seizure
duration. Deletion of CB1R from GABAergic forebrain neurons resulted in the
opposite effect. Along with these findings, the CB1R density was elevated in
animals with repetitively induced seizures. However, neither genetic nor
pharmacological interventions had any impact on the development of generalized
seizures. Other than CB1, genetic deletion or pharmacological blockade with
SB366791 (1 mg/kg) of transient receptor potential vanilloid receptor 1 (TRPV1)
had no effect on the duration of behavioral or electrographic seizure activity in
the kindling model. In conclusion, we demonstrate that endocannabinoid, but not
endovanilloid, signaling affects termination of seizure activity, without
influencing seizure severity over time. These effects are dependent on the
neuronal subpopulation. Thus, the data argue that the endocannabinoid system
plays an active role in seizure termination but does not regulate
epileptogenesis.
PMID- 25123338
TI - NK-derived IFN-gamma/IL-4 triggers the sexually disparate polarization of
macrophages in CVB3-induced myocarditis.
AB - Coxsackievirus B3 (CVB3) is a common etiology of myocarditis with an increased
morbidity and mortality in males. We previously reported that differential
polarization of macrophages contributed to sexually dimorphic susceptibility of
mice to CVB3-induced myocarditis. However, the underlying kinetics, impetus as
well as the molecular mechanism remain unclear. Here, we demonstrated that
myocardial macrophages started to polarize at as early as day 5 post CVB3
infection in both genders of BALB/c mice, with M1 phenotype detected in males and
M2a phenotype in females, and this trend was further amplified at day 7 when
myocarditis reached peak. In addition, we identified that prevailed IFN-gamma in
males and dominant IL-4 in females were critical myocardial cytokines for the
disparate macrophage polarization, which respectively activated JAK1-STAT1 and
JAK3-STAT6 pathways. Strikingly, we found that the main source of IFN-gamma and
IL-4 cytokines in both genders were myocardial infiltrating NK cells, which
differentially secreted cytokines in various microenvironments manifested
synergistically by sex hormones and CVB3 infection. Consistently, depletion of NK
cells significantly impeded the myocardial macrophage polarization in both
genders of CVB3-infected mice. Collectively, these data indicated that myocardial
NK-derived IFN-gamma/IL-4 was critical for the differential polarization of
macrophages in CVB3-induced myocarditis via activating JAK1-STAT1 and JAK3-STAT6
pathways respectively. Our study may help understand the mechanism of sexually
differential polarization of macrophages and provide clues for the gender bias in
CVB3-induced myocarditis.
PMID- 25123339
TI - The link between pediatric heart failure and mitochondrial lipids.
PMID- 25123340
TI - Psychometric evaluation of the Marijuana Reduction Strategies Self-Efficacy Scale
with young recreational marijuana users.
AB - INTRODUCTION: This study evaluated the cue-reactivity and several psychometric
properties of a questionnaire designed to assess marijuana users' self-efficacy
to employ 21 specific cognitive-behavioral strategies to reduce their marijuana
use. METHOD: Using a web-based recruitment and data-collection procedure, 513
regular marijuana users completed dependent measures following marijuana-related
or control cue exposure. RESULTS: Although exposure to marijuana-related stimuli
significantly increased reported craving, mean reduction-strategy self-efficacy
scores did not differ as a function of cue exposure. Reliability analyses
supported retaining all 21 items as a single scale. Reduction-strategy self
efficacy was positively associated with marijuana-refusal self-efficacy and with
recent past use of reduction strategies, was negatively associated with quantity
and frequency of marijuana use and marijuana-related problems, and was positively
but weakly associated with general self-efficacy. The most frequently reported
strategies that were employed reflected restricting marijuana use to once per
day, not keeping a large stash available, turning down unwanted hits, and not
obtaining more marijuana right away if one's supply runs out. CONCLUSIONS: These
findings further support the reliability and validity of the questionnaire when
administered to a diverse sample of regular marijuana users.
PMID- 25123341
TI - ADHD as a risk factor for early onset and heightened adult problem severity of
illicit substance use: an accelerated gateway model.
AB - The primary aims of the present study were to assess ADHD history as a risk
factor for earlier initiation and current use of licit and illicit substances
among a sample of drug using adults. It was hypothesized that ADHD history would
accelerate the Gateway Theory of drug use. Participants included 941 drug-using
African American and Caucasian individuals in Baltimore, Maryland. The sample
consisted of 124 (13.2%) participants who reported a history of ADHD and 817
(86.8%) who reported no history of ADHD. The accelerated gateway hypothesis was
supported, as a history of self-reported ADHD was significantly associated with
younger ages of initiation for alcohol, cigarettes, marijuana, and cocaine use.
Participants with a history of ADHD were also more likely to engage in recent HIV
risk behavior, such as injection drug use and needle sharing. This study provides
compelling data in support of an accelerated gateway model for substance use
related to ADHD history and increased problem severity in adulthood. Targeted
substance use prevention and intervention may be beneficial for those with ADHD.
PMID- 25123342
TI - It depends on when you ask: motives for using marijuana assessed before versus
after a marijuana use event.
AB - BACKGROUND: Marijuana use motives are typically evaluated retrospectively using
measures that summarize or generalize across episodes of use, which may
compromise validity. Using Ecological Momentary Assessment data, we examined the
main reason for a specific marijuana use event measured both prospectively and
retrospectively. We then determined reason types, event characteristics, and user
characteristics that predicted change in reason. METHODS: Thirty-six medical
outpatients age 15 to 24 years who used marijuana two times a week or more used a
handheld computer to select their main reason for use from the five categories of
the Marijuana Motives Measure (Simons, Correia, & Carey, 1998) just before and
after each time they used marijuana over two weeks (n=263 events with
before/after reason). The reasons were examined individually and according to
dimensions identified in motivational models of substance use (positive/negative,
internal/external). RESULTS: The reason assessed before use changed to a
different reason after use for 20% of events: 10% of events for pleasure; 21%, to
cope; 35%, to be more social; 55%, to expand my mind; and 100%, to conform. In
the multivariable model, external and expansion reasons each predicted change in
reason for use (p<0.0001 and p=0.001, respectively). Youth were also more likely
to change their reason if older (p=0.04), if male (p=0.02), and with weekend use
(p=0.002). CONCLUSION: Retrospective assessments of event-specific motives for
marijuana use may be unreliable and therefore invalid for a substantial minority
of events, particularly if use is for external or expansion reasons.
PMID- 25123343
TI - Cannabis use and suicidal ideations in high-school students.
AB - BACKGROUND: The association of cannabis use and suicidal ideations in adolescents
has been inconsistent. This discrepancy may reflect differences in controlled
confounders. In particular, no study has controlled for personality disorder
traits linked to both cannabis use and suicidality such as borderline and
psychopathic personality traits. METHOD: Participants were 972 high-school
students who completed questionnaires assessing cannabis use, suicidal ideations,
depressive symptoms, social anxiety symptoms, and borderline and psychopathic
personality traits. RESULTS: Cannabis use was not a significant independent
predictor of suicidal ideations after adjustment for confounding personality
traits in the total sample and in the subsample of cannabis users.
PMID- 25123344
TI - Differences in quit attempts between non-Hispanic Black and White daily smokers:
the role of smoking motives.
AB - INTRODUCTION: The prevalence of smoking across racial/ethnic groups has declined
over the years, yet racial health disparities for smoking persist. Studies
indicate that non-Hispanic Black smokers attempt to quit smoking more often
compared to non-Hispanic White smokers but are less successful at doing so.
Research suggests that motives to quit smoking differ by race, however, less is
known about the role of motives to smoke in explaining racial differences in
attempts to quit smoking. METHODS: This study examined whether smoking motives
accounted for the differential rates in quit attempts between non-Hispanic Black
(n=155) and non-Hispanic White (n=159) smokers. Data were culled from a larger
study of heavy-drinking smokers. The Wisconsin Index of Smoking Dependence
Motives (WISDM) assessed motives to smoke. RESULTS: As expected, Black and White
smokers reported similar smoking patterns, yet Black smokers reported higher
rates of failed attempts to quit smoking than White smokers. Findings indicated
that Black, compared to White, smokers endorsed lower scores in the negative
reinforcement, positive reinforcement, and taste WISDM subscales and scores in
these subscales mediated the relationship between race and quit attempts.
CONCLUSIONS: In this study, Blacks, compared to Whites, endorsed lower motives to
smoke, which are generally associated with successful quit attempts, yet they
experienced more failed attempts to quit smoking. This study demonstrates racial
health disparities at the level of smoking motives and suggests that Black
smokers remain vulnerable to failed quit attempts despite reporting lower motives
to smoke.
PMID- 25123345
TI - Violent offending severity among injecting drug users: examining risk factors and
issues around classification.
AB - OBJECTIVE: There is a paucity of research as to how injecting drug users (IDU)
might be differentiated in the severity of their violent offending. This paper
reported on the risks associated with severity, as well as issues around severity
classification and the impact on observed relationships with known major risk
factors. METHOD: A cross-sectional survey administered to 300 IDU, who had
injected drugs weekly or more in the past 12months. A structured questionnaire
addresses potential substance use and early-life risk factors for violent
offending. RESULTS: Four severity groups were identified: non-violent (24%), low
(34%), moderate (22%) and high (20%) level offenders. Higher severity groups had
more prevalent and more severe histories of childhood maltreatment, child
psychopathology and dysfunctional trait personalities, as well as more severe
substance use problems than low-level and non-violent IDU. Regression analyses
found that only two of 15 risk factors remained uniformly associated with violent
offending across the four classification schemes tested: (1) having committed
violence under the influence and (2) having more impulsive trait personalities.
CONCLUSIONS: Disaggregating IDU into distinct subgroups showed that the extent
and severity of predispositional and substance use risk exposure corresponded to
the severity of violent offending. There is a need to establish a systematic
method for classifying severity given that there were clinically meaningful
differences between groups which require further exploration and replication, and
because there was extensive variation in the risks associated with severity
across schemes.
PMID- 25123346
TI - Typology of driving-under-the-influence (DUI) offenders revisited: Inclusion of
DUI-specific attitudes.
AB - OBJECTIVES: Much work remains to improve rehabilitative interventions for driving
under-the-influence (DUI) offenders. There is heterogeneity of patterns of
alcohol use, personality, and driving behaviour within DUI offenders, but little
is known about how their appraisal of DUI differs. This study investigated within
offender variability in DUI-specific attitudinal variables. METHOD: Convicted
male DUI offenders (N=219) living in greater Tokyo were interviewed. Cluster
analysis was undertaken using age, psychological distress, personality trait,
alcohol use, and attitudes towards DUI. Discriminant function analysis explored
the relative explanatory power of the grouping variables. RESULT: Many offenders
reported current excessive alcohol consumption. About 26-36% of the participants
were potentially alcohol-dependent based on screening instruments/biomarkers.
Cluster analysis identified five subgroups. The biggest subgroup considered their
DUI a singular mistake and reported strong self-efficacy for avoiding further DUI
(clusters 1 and 2). A small subgroup manifested alcohol dependence, psychological
distress, higher impulsivity, and lower self-efficacy for avoiding DUI (cluster
3). Another subgroup exhibited a tendency to rationalise DUI, higher likelihood
of future DUI, and lower self-efficacy for avoiding DUI (cluster 4). Most
participants in another small subgroup abstained from alcohol use temporarily
after their convictions (cluster 5). CONCLUSION: The majority of DUI offenders
regarded their DUI conviction as an exceptional mishap, while they continued
consuming hazardous amounts of alcohol. DUI-specific attitudinal variables,
including DUI rationalisation and self-efficacy for avoiding future DUI
incidents, constituted a distinct aspect of the problem, suggesting the need to
address this issue in addition to the underlying alcohol use problem.
PMID- 25123347
TI - Comparing college smokers' and dual users' expectancies towards cigarette
smoking.
AB - BACKGROUND: As no agreed upon definition exists for dual use (i.e., individuals
who concurrently use more than one form of tobacco), this population remains
largely unstudied in the substance use literature, despite increases in smokeless
tobacco use among young adults. Individuals 18-25years of age report the highest
rates of smokeless tobacco use, dual use, and cigarette use. The current study
compared the smoking outcome expectancies of college student dual users to those
who reported only smoking cigarettes. METHODS: The Short Form of the Smoking
Consequences Questionnaire was used to examine potential differences in positive
or negative expectations regarding cigarette use. RESULTS: Data from this study
suggest that smokers believe that smoking will lead to greater positive
consequences ("cigarettes taste good"), negative reinforcement ("cigarettes help
me deal with anger"), and weight/appetite reduction ("smoking controls my
appetite") when compared to dual users. Conversely, dual users believed that
smoking would lead to greater negative consequences (e.g., "smoking is taking
years off of my life"). DISCUSSION: These results may help to explain why some
smokers choose not to use smokeless tobacco products for harm reduction or
smoking cessation purposes, as well as why increases are being observed in
smokeless tobacco rates among young adults.
PMID- 25123348
TI - Neurobiological correlates of physical self-concept and self-identification with
avatars in addicted players of Massively Multiplayer Online Role-Playing Games
(MMORPGs).
AB - AIMS: MMORPG addiction has been associated with self-concept impairments and
increased identification with the own avatar. Yet, the underlying neurobiological
mechanisms of self-identification with avatars, especially reflected in the left
angular gyrus (AG), have only been assessed in regular gamers. Therefore, the
study aims to examine neurobiological processes in addicted MMORPG players while
evaluating their own and their personal avatar's body image (physical self
concept). METHODS: Sixteen addicted and seventeen non-addicted gamers underwent
functional Magnetic Resonance Imaging (fMRI) while viewing images of themselves,
their own avatar and unfamiliar persons. The Body Image Questionnaire (FKB-20)
and Visual Analog Scales (VAS) assessing the degree of attractiveness, sympathy
and gender identity of the self, of the avatar as well as of the unfamiliar
persons were applied. RESULTS: Addicts showed a significantly extended negative
body image and lower gender identity levels as well as decreased bilateral brain
activations in the AG and the middle occipital gyrus during self-perception. They
further exhibited higher activations in the left AG during avatar-perception.
Regression analyses in the overall group and in addicted gamers indicated a
significant positive correlation between gender identity and brain activation in
the left AG during self-perception. CONCLUSIONS: Our results confirm addicted
MMORPG players to have physical self-concept deficits which may be related to
hypoactivations in the AG. The findings further indicate addicted gamers to have
a tendency to identify themselves easier with their own avatar than with their
real self. Lower gender identity levels might be associated with physical self
concept deficits in MMORPG addiction.
PMID- 25123349
TI - Alcohol use, impulsivity, and the non-medical use of prescription stimulants
among college students.
AB - The non-medical use of prescription drugs (NMUPD) is a growing public health
concern. College students have been identified as a particularly at risk
population for engagement in NMUPD. Across all prescription drug classes,
stimulants show the highest ratio of illicit to medical use and are thus
important to examine within this population. Emerging research has suggested a
relationship between the non-medical use of prescription stimulants (NMUPS) and
alcohol use within the college student population. Finally, the construct of
impulsivity may serve as an additional indicator for students who engage in NMUPS
as well as those who engage in NMUPS/alcohol co-ingestion. The purpose of this
paper is to expand on previous prevalence data collected for the past year NMUPS
and NMUPS/alcohol co-ingestion. Additionally, this paper examines whether those
who engage in NMUPS or NMUPS/alcohol co-ingestion differ significantly from their
non-using counterparts on measures of alcohol use, alcohol related negative
consequences, binge drinking, and impulsivity. Finally, binary logistic
regression models indicated that increased alcohol use, alcohol related negative
consequences, and impulsivity all significantly increase the odds of an
individual engaging in NMUPS or NMUPS/alcohol co-ingestion.
PMID- 25123350
TI - From hundreds to thousands: Widening the normal human Urinome (1).
AB - It is currently unknown how many proteins can be detected in urine. Improving the
analytical approach would increase their number and potentially strengthen their
predictive potential in diseases. We developed a combination of analytical
procedures for maximizing sensitivity and reproducibility of normal human urinary
proteome analysis based on ultracentrifugation, vesicles separation,
combinatorial peptide ligand libraries (CPLL) and solvent removal of pigments.
Proteins were identified by an Orbitrap Velos Mass Spectrometry. Overall, 3429
proteins were characterized: most components (1615) were contained in vesicles
while the remaining 1794 were equally distributed among CPLL and butanol
insoluble fractions. Several proteins were detected exclusively in one of the
phases of the procedure, suggesting that each step is crucial in the
fractionation strategy. Many (1724) proteins are described here whose presence in
urine has never been reported and represents a potential source of information
considering that urine is the unique site of excretion of products of interaction
of metabolic processes. Improving the characterization of normal urinary proteome
would also represent the basis for the analysis of urine biomarkers in human
diseases. BIOLOGICAL SIGNIFICANCE: Sub-fractionating normal urine by successive
steps (vesicle separation, CPLL and solvent treatments) allowed the
identification of 3429 proteins, a relevant part (1724) being detected for the
first time in urine. Several proteins of new description have been implicated in
physiology pathways and in pathologies thus representing a potential source of
new information on both metabolic processes and diseases.
PMID- 25123351
TI - Extended bottom-up proteomics with secreted aspartic protease Sap9.
AB - We investigate the benefits and experimental feasibility of approaches enabling
the shift from short (1.7 kDa on average) peptides in bottom-up proteomics to
about twice longer (~3.2 kDa on average) peptides in the so-called extended
bottom-up proteomics. Candida albicans secreted aspartic protease Sap9 has been
selected for evaluation as an extended bottom-up proteomic-grade enzyme due to
its suggested dibasic cleavage specificity and ease of production. We report the
extensive characterization of Sap9 specificity and selectivity revealing that
protein cleavage by Sap9 most often occurs in the vicinity of proximal basic
amino acids, and in select cases also at basic and hydrophobic residues. Sap9 is
found to cleave a large variety of proteins in a relatively short, ~1 h, period
of time and it is efficient in a broad pH range, including slightly acidic, e.
g., pH5.5, conditions. Importantly, the resulting peptide mixtures contain
representative peptides primarily in the target 3-7 kDa range. The utility and
advantages of this enzyme in routine analysis of protein mixtures are
demonstrated and the limitations are discussed. Overall, Sap9 has a potential to
become an enzyme of choice in an extended bottom-up proteomics, which is
technically ready to complement the traditional bottom-up proteomics for improved
targeted protein structural analysis and expanded proteome coverage. BIOLOGICAL
SIGNIFICANCE: Advances in biological applications of mass spectrometry-based
bottom-up proteomics are oftentimes limited by the extreme complexity of
biological samples, e.g., proteomes or protein complexes. One of the reasons for
it is in the complexity of the mixtures of enzymatically (most often using
trypsin) produced short (<3 kDa) peptides, which may exceed the analytical
capabilities of liquid chromatography and mass spectrometry. Information on
localization of protein modifications may also be affected by the small size of
typically produced peptides. On the other hand, advances in high-resolution mass
spectrometry and liquid chromatography have created an intriguing opportunity of
improving proteome analysis by gradually increasing the size of enzymatically
derived peptides in MS-based bottom-up proteomics. Bioinformatics has already
confirmed the envisioned advantages of such approach. The remaining bottle-neck
is an enzyme that could produce longer peptides. Here, we report on the
characterization of a possible candidate enzyme, Sap9, which may be considered
for producing longer, e.g., 3-7 kDa, peptides and lead to a development of
extended bottom-up proteomics.
PMID- 25123352
TI - Caries-preventive effectiveness of fluoride varnish as adjunct to oral health
promotion and supervised tooth brushing in preschool children: a double-blind
randomized controlled trial.
AB - OBJECTIVES: To evaluate the effect of biannual fluoride varnish applications in
preschool children as an adjunct to school-based oral health promotion and
supervised tooth brushing with 1000ppm fluoride toothpaste. METHODS: 424
preschool children, 2-5 year of age, from 10 different pre schools in Athens were
invited to this double-blind randomized controlled trial and 328 children
completed the 2-year programme. All children received oral health education with
hygiene instructions twice yearly and attended supervised tooth brushing once
daily. The test group was treated with fluoride varnish (0.9% diflurosilane)
biannually while the control group had placebo applications. The primary
endpoints were caries prevalence and increment; secondary outcomes were gingival
health, mutans streptococci growth and salivary buffer capacity. RESULTS: The
groups were balanced at baseline and no significant differences in caries
prevalence or increment were displayed between the groups after 1 and 2 years,
respectively. There was a reduced number of new pre-cavitated enamel lesions
during the second year of the study (p=0.05) but the decrease was not
statistically significant. The secondary endpoints were unaffected by the varnish
treatments. CONCLUSIONS: Under the present conditions, biannual fluoride varnish
applications in preschool children did not show significant caries-preventive
benefits when provided as an adjunct to school-based supervised tooth brushing
with 1000ppm fluoride toothpaste. CLINICAL SIGNIFICANCE: In community based,
caries prevention programmes, for high caries risk preschool children, a fluoride
varnish may add little to caries prevention, when 1000ppm fluoride toothpaste is
used daily.
PMID- 25123353
TI - ASC, a bioactive steroidal saponin from Ophitopogin japonicas, inhibits
angiogenesis through interruption of Src tyrosine kinase-dependent matrix
metalloproteinase pathway.
AB - As angiogenesis is an important target for antitumour drugs, the agents that
inhibit angiogenesis may help reduce the use of chemotherapy by blocking tumour
blood supply. In this study, we investigated a potent angiogenesis inhibitor,
ASC, a steroidal saponin compound, which has been purified from Ophitopogin
japonicus (L.f) Ker.-Gawl. Our observations showed that ASC significantly
suppressed human umbilical vein endothelial cell (HUVECs) growth both in vitro
and in vivo. This may be resulted from the G2/M cell cycle arrest effects of ASC.
Moreover, ASC inhibited HUVECs invasion and tube formation processes, which were
associated with endothelial cells remodelling. A mechanism study indicated that
ASC down-regulated the expression of Src tyrosine kinase, further leading to the
blockage of Akt-dependent matrix metalloproteinases (mainly for MMP-9) signalling
pathway, which was functionally associated with angiogenic blood vessels.
Finally, ASC significantly inhibited angiogenesis and MMPs/VEGF expression in the
subcutaneously injected matrigel in C57/BL mice. These findings suggest that ASC
might be a potential drug candidate in anti-angiogenesis and anticancer
therapies.
PMID- 25123354
TI - The influence of eating disorders on mothers' sensitivity and adaptation during
feeding: a longitudinal observational study.
AB - BACKGROUND: Parents with past and current eating disorders (ED) have been shown
to report troubles nourishing their infants. This could increase the risk of
infant feeding problems linked to maternal anxiety and depression. It is not
clear how mothers' eating difficulties before pregnancy and at the time of birth
can affect infant's feeding. We aimed to specify the impact of eating disorders
on mothers' adaptation and sensitivity to their offspring during feeding, by
comparing a population of mothers with eating disorders and controls. METHODS:
Twenty-eight women agreed to participate in interviews and filmed mother-baby
interactions. Pregnant women consulting at an obstetric unit for care follow-up
were screened and tested for symptoms of eating disorders with the EDE-Q
Questionnaire (Eating Disorders Examination Questionnaire) and the EDE Interview
(Eating Disorders Examination Interview). Infant functional troubles and mothers'
sensitivity were investigated through the Symptom Check List. Reciprocal
adaptation during feeding with their new-borns was filmed and analysed with the
Chatoor Infant Feeding Scale. Before pregnancy, two women suffered from anorexia,
three suffered from bulimia, three had binge eating symptoms and two were
diagnosed with EDNOS (Eating Disorders Not Otherwise Specified). RESULTS: Mothers
suffering from ED tended to show more difficult interactive patterns in terms of
dyadic reciprocity when feeding their babies compared with mothers with no
symptoms of eating disorders. In the interviews, other than the behavioural data
gathered, ED mothers expressed feeling more dissatisfaction and uneasiness during
feeding. CONCLUSIONS: Pregnancy seems to be an useful period for interviewing
women on eating disorders, allowing for the design and implementation of
prevention programmes based on mothers' narratives and infant/mother observations
and treatment.
PMID- 25123355
TI - Intracolonial genetic variation affects reproductive skew and colony productivity
during colony foundation in a parthenogenetic termite.
AB - BACKGROUND: In insect societies, intracolonial genetic variation is predicted to
affect both colony efficiency and reproductive skew. However, because the effects
of genetic variation on these two colony characteristics have been tested
independently, it remains unclear whether they are affected by genetic variation
independently or in a related manner. Here we test the effect of genetic
variation on colony efficiency and reproductive skew in a rhinotermitid termite,
Reticulitermes speratus, a species in which female-female pairs can facultatively
found colonies. We established colonies using two types of female-female pairs:
colonies founded by sisters (i.e., sister-pair colonies) and those founded by
females from different colonies (i.e., unrelated-pair colonies). Colony growth
and reproductive skew were then compared between the two types of incipient
colonies. RESULTS: At 15 months after colony foundation, unrelated-pair colonies
were larger than sister-pair colonies, although the caste ratio between workers
and nymphs, which were alternatively differentiated from young larvae, did not
differ significantly. Microsatellite DNA analyses of both founders and their
parthenogenetically produced offspring indicated that, in both sister-pair and
unrelated-pair colonies, there was no significant skew in the production of eggs,
larvae, workers and soldiers. Nymph production, however, was significantly more
skewed in the sister-pair colonies than in unrelated-pair colonies. Because
nymphs can develop into winged adults (alates) or nymphoid reproductives, they
have a higher chance of direct reproduction than workers in this species.
CONCLUSIONS: Our results support the idea that higher genetic variation among
colony members could provide an increase in colony productivity, as shown in
hymenopteran social insects. Moreover, this study suggests that low genetic
variation (high relatedness) between founding females increases reproductive skew
via one female preferentially channeling her relatives along the reproductive
track. This study thus demonstrated that, in social insects, intracolonial
genetic variation can simultaneously affect both colony efficiency and
reproductive skew.
PMID- 25123356
TI - Self-adhesive epidermal carbon nanotube electronics for tether-free long-term
continuous recording of biosignals.
AB - The long-term, continuous, inconspicuous, and noiseless monitoring of
bioelectrical signals is critical to the early diagnosis of disease and
monitoring health and wellbeing. However, it is a major challenge to record the
bioelectrical signals of patients going about their daily lives because of the
difficulties of integrating skin-like conducting materials, the measuring system,
and medical technologies in a single platform. In this study, we developed a thin
epidermis-like electronics that is capable of repeated self-adhesion onto skin,
integration with commercial electronic components through soldering, and
conformal contact without serious motion artifacts. Using well-mixed carbon
nanotubes and adhesive polydimethylsiloxane, we fabricated an epidermal carbon
nanotube electronics which maintains excellent conformal contact even within
wrinkles in skin, and can be used to record electrocardiogram signals robustly.
The electrode is biocompatible and can even be operated in water, which means
patients can live normal lives despite wearing a complicated recording system.
PMID- 25123358
TI - Unilateral ear and temporomandibular joint discomfort.
PMID- 25123357
TI - Re-irradiation of recurrent glioblastoma multiforme using 11C-methionine
PET/CT/MRI image fusion for hypofractionated stereotactic radiotherapy by
intensity modulated radiation therapy.
AB - BACKGROUND: This research paper presents a valid treatment strategy for recurrent
glioblastoma multiforme (GBM) using hypofractionated stereotactic radiotherapy by
intensity modulated radiation therapy (HS-IMRT) planned with 11C-methionine
positron emission tomography (MET-PET)/computed tomography (CT)/magnetic
resonance imaging (MRI) fusion. METHODS: Twenty-one patients with recurrent GBM
received HS-IMRT planned by MET-PET/CT/MRI. The region of increased amino acid
tracer uptake on MET-PET was defined as the gross tumor volume (GTV). The
planning target volume encompassed the GTV by a 3-mm margin. Treatment was
performed with a total dose of 25- to 35-Gy, given as 5- to 7-Gy daily for 5
days. RESULTS: With a median follow-up of 12 months, median overall survival time
(OS) was 11 months from the start of HS-IMRT, with a 6-month and 1-year survival
rate of 71.4% and 38.1%, respectively. Karnofsky performance status was a
significant prognostic factor of OS as tested by univariate and multivariate
analysis. Re-operation rate was 4.8% for radiation necrosis. No other acute or
late toxicity Grade 3 or higher was observed. CONCLUSIONS: This is the first
prospective study of biologic imaging optimized HS-IMRT in recurrent GBM. HS-IMRT
with PET data seems to be well tolerated and resulted in a median survival time
of 11 months after HS-IMRT.
PMID- 25123359
TI - Reduction in C-terminal amidated species of recombinant monoclonal antibodies by
genetic modification of CHO cells.
AB - BACKGROUND: During development of recombinant monoclonal antibodies in Chinese
hamster ovary (CHO) cells, C-terminal amidated species are observed. C-terminal
amidation is catalysed by peptidylglycine alpha-amidating monooxygenase (PAM), an
enzyme known to be expressed in CHO cells. The significant variations between
clones during clone selection, and the relatively high content of amidated
species (up to 15%) in comparison to reference material (4%), led us to develop a
cell line with reduced production of C-terminal amidated monoclonal antibodies
using genetic manipulation. RESULTS: Initial target validation was performed
using the RNA interference approach against PAM, which resulted in a CHO cell
line with C-terminal amidation decreased to 3%. Due to the transient effects of
small-interfering RNAs, and possible stability problems using short-hairpin RNAs,
we knocked-down the PAM gene using zinc finger nucleases. Plasmid DNA and mRNA
for zinc finger nucleases were used to generate a PAM knock-out, which resulted
in two CHO cell lines with C-terminal amidation decreased to 6%, in CHO Der2 and
CHO Der3 cells. CONCLUSION: Two genetically modified cell lines were generated
using a zinc finger nuclease approach to decrease C-terminal amidation on
recombinant monoclonal antibodies. These two cell lines now represent a pool from
which the candidate clone with the highest comparability to the reference
molecule can be selected, for production of high-quality and safe therapeutics.
PMID- 25123360
TI - Understanding the experience of myotonic dystrophy. Mixed method study.
AB - Myotonic dystrophy (DM) is a progressive multi-systemic disorder characterized by
myotonia and muscle weakness where currently no effective treatment or cure to
prevent or delay the disorder exists. This study used mixed methods to examine
the experience of living with DM, in patients and their close relatives. Thirteen
patients and eight next of kin responded completing Quality of Life and
Psychological distress questionnaires in this cross-sectional study, and
participating in a semi-structured interview. The findings indicate a higher
level of anxiety and hopelessness in next of kin compared to patients, while
patients were more depressed. Next of kin reported higher physical, but lower
emotional quality of life than patients. Qualitative interviews confirmed the
questionnaire findings. The findings from this study may be helpful in genetic
counseling. Genetic counselors and geneticists should not only be aware of the
burden of being a next of kin, but include discussions about opportunities to
minimize the burden in families affected with DM. The findings may be of
relevance in counseling for other types of neuromuscular disorders.
PMID- 25123362
TI - Enhanced bioconversion of ethylene glycol to glycolic acid by a newly isolated
Burkholderia sp. EG13.
AB - Burkholderia sp. EG13 with high ethylene glycol-oxidizing activity was isolated
from soil, which could be used for the synthesis of glycolic acid from the
oxidation of ethylene glycol. Using the resting cells of Burkholderia sp. EG13 as
biocatalysts, the optimum reaction temperature and pH were 30 degrees C and 6.0,
respectively. After 24 h of biotransformation, the yield of glycolic acid from
200 mM ethylene glycol was 98.8 %. Furthermore, an integrated bioprocess for the
production of glycolic acid which involved in situ product removal (ISPR) was
investigated. Using fed-batch method with ISPR, a total of 793 mM glycolic acid
has been accumulated in the reaction mixture after the 4th feed.
PMID- 25123361
TI - Tracing the emergence of multidrug-resistant Acinetobacter baumannii in a
Taiwanese hospital by evaluating the presence of integron gene intI1.
AB - BACKGROUND: In Changhua County, Taiwan, the number of clinical Acinetobacter
baumannii isolates has risen since 2002, and multidrug-resistant Acinetobacter
baumannii (MDRAB) has spread rapidly throughout Taiwan. In this study, to reveal
the mechanism involved with the rapid dissemination of MDRAB emergence, the
utility of the class 1 integron, intI1 integrase gene, as an MDRAB-associated
biomarker was examined. A cross-sectional, clinical epidemiological study was
performed at Changhua Christian Hospital between January 1st, 2001 and December
31st, 2004. Besides the existence of intI1 gene was examined, the pulse-field gel
electrophoresis (PFGE) was also performed to determine the epidemiological
characteristics of the isolates. FINDINGS: The overall hospital infection rate
was 5-6%, while the infection rate of the intensive care unit (ICU) fluctuated.
No positive correlation was observed between MDRAB isolates and the presence of
intI1 (r = 0.168, P = 0.254). Additionally, no positive correlation was observed
between the infection rate in the ICU and the presence of intI1 (r = -0.107, P =
0.468) or between the hospital infection rate and the presence of intI1 (r =
0.189, P = 0.199). However, two predominant clones among the MDRAB isolates were
identified by PFGE. CONCLUSIONS: Although the presence of the intI1 gene does not
seem suitable for tracing MDRAB emergence in Changhua County, two predominant
clones were identified by PFGE, and subsequent studies to identify whether these
clones were responsible for original nosocomial infection are needed.
PMID- 25123363
TI - High overexpression and purification of optimized bacterio-opsin from
Halobacterium Salinarum R1 in E. coli.
AB - The purple membrane of Halobacterium Salinarum carries out a protein,
bacteriorhodopsin (bR), which is a model for structure-function studies of
membrane proteins. The heterologous expression of integral membrane proteins
(IMPS) is difficult. In this study, we reported the heterologous overexpression
of bacterio-opsin (bO) in Escherichia coli BL21 (DE3). Bacterio-opsin expression
is facilitated by using mistic, a membrane protein from Bacillus subtilis in E.
coli BL21 (DE3) membranes. The optimized bO gene was cloned in fusion to the C
terminus of mistic in pET 30a (+) and contains an oct-histidine in C-terminal to
facilitate purification. Different medium, temperature, and induction time were
used to optimize protein overexpression. The highest expression was obtained from
the Terrific Broth (TB) medium at 18 degrees C with an IPTG concentration of 0.1
mM. The final purified bR was 192 +/- 1 mg/L which has an important value for the
production of membrane proteins in E. coli.
PMID- 25123364
TI - Improved pretreatment process using an electron beam for optimization of glucose
yield with high selectivity.
AB - In this study, electron beam irradiation (EBI) assisted by a dilute acid
pretreatment process was investigated to improve the glucose yield and show high
selectivity in the enzymatic hydrolysis of rice straw. In the first step, EBI of
rice straw was performed at various doses ranging from 50 to 500 kGy. The
electron beam-irradiated rice straw was then autoclaved with 3 % dilute acid at
120 degrees C for 1 h. The pretreated rice straw was finally subjected to
enzymatic hydrolysis at 50 degrees C for 24, 48, and 72 h by 70 filter paper
units (FPU)/mL cellulase and 40 cellobiose units (CbU)/mL glucosidase. Glucose
was obtained with a very high selectivity of 92.7 % and a total sugar yield of 80
% from pretreated rice straw after 72 h of enzymatic hydrolysis.
PMID- 25123365
TI - Temperature Dependence of the Complexation Mechanism of Celecoxib and Hydroxyl
beta-cyclodextrin in Aqueous Solution.
AB - Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) is commonly used as a complexation
reagent to solubilize compounds with poor aqueous solubility to improve in vivo
dosing. However, the degree of solubility enhancement was often limited by the
formation of only a 1:1 complex and a low complexation constant (K). Such a
limitation can be significantly improved by the formation of 1:2 complexes in
some cases. Despite the understanding of the solubility advantage of the
formation of the 1:2 complexes, there is no systematic understanding that could
drive for the formation of 1:2 complexes. Thus, in most cases, the formation of
1:2 complexes was limited by observation bases. In this study, we pioneer the
usages of molecular dynamics (MD) simulation to understand the phenomena of a
model drug of celecoxib (CCB) and HP-beta-CD. It has been reported that celecoxib
(CCB) forms 1:1 complexes with cyclodextrin in solution; however, some data
suggest the existence of a 1:2 complex. The simulation results suggest that a
transition state of CCB and HP-beta-CD may exit at a higher temperature of CCB
and HP-beta-CD; a model drug, such as celecoxib (CCB), that is known to form 1:1
complexes can achieve a higher degree of complexation (1:2) and obtain much
improved solubility when the same amount of cyclodextrin was used and
demonstrated in vitro. The simulation results of CCB and HP-beta-CD could be a
model system that may provide important insights into the inclusion mechanism.
PMID- 25123367
TI - [Hereditary transthyretin amyloidosis].
AB - Hereditary amyloidosis is an autosomal dominant fatal multisystem disease caused
by extracellular deposition of misfolded proteins and, therefore represents a
hereditary protein folding or deposition disease that leads to progressive organ
damage and eventually death. In most instances mutations within the transthyretin
gene are the underlying cause. The main manifestation is a rapidly progressing
axonal sensorimotor and autonomic polyneuropathy (familial amyloid
polyneuropathy, FAP). Cardiac involvement is frequent in FAP and additional
manifestations include the gastrointestinal tract and the eyes. A second
manifestation type is cardiomyopathy with little or no polyneuropathy (familial
amyloid cardiomyopathy, FAC). For therapy, orthotopic liver transplantation has
been established for 25 years. Recently, the oral agent tafamidis, a
transthyretin stabilizer, was licensed for treatment of stage 1 polyneuropathy.
Additional treatment options are currently being studied.
PMID- 25123368
TI - [Spirituality in schizophrenic diseases].
AB - OBJECTIVE: The aim of this study was to investigate different dimensions of
religiosity and spirituality among schizophrenic inpatients (F 2x) compared to
addiction patients (F 10.2, F 19.2) and to healthy controls. In addition the
dimensions of religious and spiritual well-being were examined and related to
different parameters of mental illness. METHOD: The group of schizophrenic
patients (n = 39) was compared to a group of addiction patients (n = 33) and a
healthy control group (n = 38) by means of the multidimensional inventory for
religious/spiritual well-being (MI-RSWB). Additionally, dimensions of RSWB were
related to the Beck depression inventory (BDI) and the brief symptom inventory
(BSI) in the group of schizophrenic patients. RESULTS: The group of schizophrenic
patients did not differ from the addiction patients or from the healthy controls
in the RSWB dimensions, except for the hope transcendent sub-dimension.
Furthermore, dimensions of RSWB turned out to be negatively correlated with the
severity of psychiatric symptoms (BDI and BSI). CONCLUSION: As assumed a positive
relationship between RSWB and subjective well-being can be confirmed also for the
group of schizophrenic patients. Existentially oriented dimensions such as hope
and forgiveness might be specifically relevant for the group of schizophrenics.
PMID- 25123366
TI - [Neurobiology of schizophrenia: new findings from the structure to the
molecules].
AB - During recent years improved methods in neuroimaging, molecular biology and
genetics contributed to new insights into the neurobiology of schizophrenia. This
review summarizes and discusses current findings and their impact on the
pathophysiology of the disease. New magnetic resonance imaging (MRI) based
methods allow investigation of small subregions of the hippocampus and structural
and functional connectivity analyses using multimodal imaging approaches. Volume
deficits are correlated with MRI spectroscopy based data of the glutamatergic and
GABAergic systems and confirm the glutamate hypothesis of schizophrenia. Due to
detailed clinical investigations, the association between brain imaging, symptom
dimensions and cognitive deficits are becoming more evident. Genome-wide
microarray assessments facilitate more detailed analyses of groups of
differentially expressed genes and will advance with the application of next
generation sequencing (NGS) and the development of inducible pluripotent stem
cells. To date a multitude of new risk genes have been detected due to genome
wide association studies, each with a small effect. Future challenges encompass
the identification of their neurobiological function and impact on neuroplastic
processes, brain structure and function. Based on such information, the
development of innovative risk-based therapy strategies is to be expected.
PMID- 25123369
TI - Model selection in historical biogeography reveals that founder-event speciation
is a crucial process in Island Clades.
AB - Founder-event speciation, where a rare jump dispersal event founds a new
genetically isolated lineage, has long been considered crucial by many historical
biogeographers, but its importance is disputed within the vicariance school.
Probabilistic modeling of geographic range evolution creates the potential to
test different biogeographical models against data using standard statistical
model choice procedures, as long as multiple models are available. I re-implement
the Dispersal-Extinction-Cladogenesis (DEC) model of LAGRANGE in the R package
BioGeoBEARS, and modify it to create a new model, DEC + J, which adds founder
event speciation, the importance of which is governed by a new free parameter,
[Formula: see text]. The identifiability of DEC and DEC + J is tested on data
sets simulated under a wide range of macroevolutionary models where geography
evolves jointly with lineage birth/death events. The results confirm that DEC and
DEC + J are identifiable even though these models ignore the fact that molecular
phylogenies are missing many cladogenesis and extinction events. The simulations
also indicate that DEC will have substantially increased errors in ancestral
range estimation and parameter inference when the true model includes + J. DEC
and DEC + J are compared on 13 empirical data sets drawn from studies of island
clades. Likelihood-ratio tests indicate that all clades reject DEC, and AICc
model weights show large to overwhelming support for DEC + J, for the first time
verifying the importance of founder-event speciation in island clades via
statistical model choice. Under DEC + J, ancestral nodes are usually estimated to
have ranges occupying only one island, rather than the widespread ancestors often
favored by DEC. These results indicate that the assumptions of historical
biogeography models can have large impacts on inference and require testing and
comparison with statistical methods.
PMID- 25123371
TI - Distal bypasses in patients with diabetes and infrapopliteal disease: technical
considerations to achieve success.
AB - The combination of diabetes and peripheral arterial disease (PAD) is challenging
in many ways. The characteristic and complex distal distribution of PAD often
encountered in patients with diabetes means that bypass surgery in this context
is technically challenging. In addition, many of these patients have a burden of
serious comorbidities that must be optimized and managed concurrently. While the
authors acknowledge that "achieving success" in distal bypass relies on much more
than technical expertise, there are some technical aspects that should be
considered when planning surgery on these patients. This article outlines some
important issues in the treatment pathway of a patient with diabetes and PAD
requiring distal bypass surgery--from selection and optimization of the patient
(in the context of a multidisciplinary team) and preoperative workup, to the
operative strategy planning, technical tips, and nonoperative adjuncts. These
considerations, as well as sound knowledge of the underlying disease process,
confounding medical factors and awareness of the difficulty in predicting
treatment outcomes, should help maximize the chances of success.
PMID- 25123372
TI - Do you want to organize a multidisciplinary diabetic foot clinic? We can help.
AB - The diabetic foot (DF) is a complex pathology involving the lower limb of 8 to 10
million people around the world, and its prevalence is rising, creating a
dramatic need for effective therapeutic answers. The multidisciplinary DF clinic
has been proposed as a model to fight this complication from the International
Working Group on Diabetic Foot (IWGDF) inside a more articulated 3-level
organization strategy. The organization and technical aspects of this strategy,
together with the characteristics of each of the 3 levels have been analyzed and
described in the article, together with the aims and limitations of each of the
levels to cope with a 3-dimensional pathology involving systemic, local, and
logistic aspects. The implementation of this model in Europe produced positive
results measured so far in at least 2 nationwide experiences, in Germany and in
Italy, and it should be taken in account whenever health policies apply to the DF
issue.
PMID- 25123370
TI - The cereal starch endosperm development and its relationship with other endosperm
tissues and embryo.
AB - The cereal starch endosperm is the central part of endosperm, and it is rich in
starch and protein which are the important resources for human food. The starch
and protein are separately accumulated in starch granules and protein bodies.
Content and configuration of starch granules and protein bodies affect the
quality of the starch endosperm. The development of starch endosperm is mediated
by genes, enzymes, and hormones, and it also has a close relationship with other
endosperm tissues and embryo. This paper reviews the latest investigations on the
starch endosperm and will provide some useful information for the future
researches on the development of cereal endosperm.
PMID- 25123373
TI - Confronting a dramatic situation: the charcot foot complicated by osteomyelitis.
AB - Charcot osteoarthropathy is a serious complication of diabetic neuropathy. Its
prevalence in the diabetic population varies in the literature in relation to
certain variables, such as the method of assessment, clinical or instrumental;
the population studied; and the scope of the selection. This article is intended
as a review of the recent literature concerning Charcot osteoarthropathy in its
evolution and complications characterized by the development of ulceration and
subsequent bone infection. Diagnosis and treatment strategies--either medical or
surgical--are discussed both for Charcot arthropathy and osteomyelitis.
PMID- 25123374
TI - Atraumatic intubation: experience using a 5.0 endotracheal tube without a stylet
for laryngeal surgery.
AB - OBJECTIVES/HYPOTHESIS: Vocal fold injury is a well-know complication of
intubation, with rates reported as high as 69%. Laryngology textbooks recommend
the use of a small endotracheal tube (ETT) to help avoid these complications and
optimize visualization. Case reports have suggested that the rigid stylet can
lead to laryngeal injury. Given the additional risks, intubation without the
stylet is our preferred practice. There is limited documentation in the
literature regarding this viewpoint. Our study investigated the feasibility of
and potential barriers to intubation using 5.0 ETT without a stylet. STUDY
DESIGN: Prospective study. METHODS: Consecutive adult patients undergoing
laryngeal surgery were recruited for intubation with a 5.0 ETT without a stylet.
Demographic data, specialty and training level of the intubator, and factors that
would predict a difficult intubation were recorded. Descriptive statistical
analysis was performed. RESULTS: Findings of the participants (n = 67) included
average American Society of Anesthesiologists (ASA) physical status
classification (2.2), average Mallampati score (1.7), average Cormack-Lehane
grade (1.5), and average body mass index (28.0). Five patients (7.4%) required
intubation using a stylet, and one of these five participants was intubated
initially with a stylet. Of these five participants, 80% required use of a
GlideScope (P < .001), and they had significantly higher ASA classification (P =
.047) and number of intubation attempts (P = .042). One patient sustained an
oropharyngeal injury during intubation with a stylet. No participants had
laryngeal injury. CONCLUSIONS: Most patients can be intubated successfully using
a 5.0 ETT without a stylet. There were no cases of laryngeal trauma with this
technique. LEVEL OF EVIDENCE: 2b.
PMID- 25123375
TI - A commercially available preparation of Staphylococcus aureus bio-products
potently inhibits tumour growth in a murine model of mesothelioma.
AB - BACKGROUND AND OBJECTIVE: Mesothelioma is an incurable cancer with a rising
global incidence. Intrapleural delivery of a commercially available compound made
up of proteins produced by Staphylococcus aureus has been used clinically to
induce pleurodesis. We investigate if this bacterial compound has anti-tumoural
activities against pleural malignancies, in addition to its pleurodesing effect.
METHODS: The effects of the treatment on mesothelioma cells were evaluated in
vitro and further tested in two validated murine models. RESULTS: This S. aureus
bio-product mixture effectively kills mesothelioma cells and induces the release
of interleukin (IL)-8, monocyte chemotactic protein (MCP)-1 and vascular
endothelial growth factor from primary human mesothelial cells but not malignant
pleural mesothelioma cells in vitro. Intratumoural delivery of the treatment in
BALB/c mice induced tumour necrosis and local activation of T cells. Tumour
growth was significantly inhibited in the treatment group during and after the
treatment period (size of tumour 58.8 +/- 10.3 mm(2) vs 118.3 +/- 6.7 mm(2) from
saline controls at day 23, n = 9-12 per group), P < 0.001. Tumour growth resumed
on cessation of treatment, confirming the inhibition was treatment related.
Treatment benefits were further validated in an orthotopic peritoneal model of
mesothelioma and the compound significantly reduced the mesothelioma load (P <
0.05 vs saline controls). Mice in the treatment group had a significant increase
in the percentage of activated CD4(+) and CD8(+) T cells in tumour-draining lymph
nodes. No histological side-effects were observed with the treatment.
CONCLUSIONS: This proof-of-principle study demonstrates promising antitumoural
activity of a commercially available compound of S. aureus bio-products against
mesothelioma.
PMID- 25123376
TI - Porous polymers based on aryleneethynylene building blocks.
AB - Porous conjugated polymers are synthesized by metal-catalyzed coupling reactions.
The progress for porous polymers when planar or tetrahedral building blocks are
connected by alkyne units into novel materials is highlighted. The most prominent
reaction for the buildup of the microporous alkyne-bridged polymers is the
Sonogashira reaction, connecting alkynes to aromatic iodides or bromides. The
availability of the building blocks and the potency of the Sonogashira reaction
allow preparing a large variety of intrinsically porous polymeric materials, in
which rigid struts connect multipronged centers. The microporous polymers are
used as catalysts and as storage materials for gases and sensors.
Postfunctionalization schemes, understanding of structure-property relationships,
and the quest for high porosity are pertinent.
PMID- 25123377
TI - Neurophysiological correlates of eye movement desensitization and reprocessing
sessions: preliminary evidence for traumatic memories integration.
AB - We have investigated the potential role of eye movement desensitization and
reprocessing (EMDR) in enhancing the integration of traumatic memories by
measuring EEG coherence, power spectra and autonomic variables before (pre-EMDR)
and after (post-EMDR) EMDR sessions during the recall of patient's traumatic
memory. Thirteen EMDR sessions of six patients with post-traumatic stress
disorder were recorded. EEG analyses were conducted by means of the standardized
Low Resolution Electric Tomography (sLORETA) software. Power spectra, EEG
coherence and heart rate variability (HRV) were compared between pre- and post
EMDR sessions. After EMDR, we observed a significant increase of alpha power in
the left inferior temporal gyrus (T = 3.879; P = 0.041) and an increased EEG
coherence in beta band between C3 and T5 electrodes (T = 6.358; P < 0.001).
Furthermore, a significant increase of HRV in the post-EMDR sessions was also
observed (pre-EMDR: 6.38 +/- 6.83; post-EMDR: 2.46 +/- 2.95; U-Test = 45, P =
0.043). Finally, the values of lagged coherence were negatively associated with
subjective units of disturbance (r(24) = -0.44, P < 0.05) and positively
associated with parasympathetic activity (r(24) = 0.40, P < 0.05). Our results
suggest that EMDR leads to an integration of dissociated aspects of traumatic
memories and, consequently, a decrease of hyperarousal symptoms [Correction made
here after initial publication].
PMID- 25123378
TI - Long term follow-up of four patients with Keutel syndrome.
AB - Keutel syndrome (KS) [OMIM 245150] is an autosomal recessive hereditary syndrome
characterized by multiple peripheral pulmonary stenoses (PPS),
brachytelephalangia, inner ear deafness, and abnormal cartilage ossification or
calcification. Mutations in the matrix Gla protein (MGP) gene have been reported
in different unrelated families with KS previously. MGP is an extracellular
matrix protein and calcification inhibitor; mutations in its encoding gene result
in cartilage ossification or calcification, the main presenting feature of KS.
This report describes the findings of four sisters with KS born to consanguineous
parents were followed for 26 years in an irregular fashion. During follow-up of
the patients over the years the complications appear to be mostly involving the
respiratory system. Permanent skin rashes, papillary microcarcinoma of the
thyroid, asthma, massive bullous pulmonary emphysema, severe systemic arterial
hypertension, and short term memory loss were observed during long term follow
up. The fertility status of the patients were also observed and infertility was
observed in one of three married patients.
PMID- 25123379
TI - Incidence of and risk factors for incisional hernia after abdominal surgery.
AB - BACKGROUND: Few larger studies have estimated the incidence of incisional hernia
(IH) after abdominal surgery. METHODS: Patients who had abdominal surgery between
November 2009 and February 2011 were included in the study. The incidence rate
and risk factors for IH were monitored for at least 180 days. RESULTS: A total
of 4305 consecutive patients were registered. Of these, 378 were excluded because
of failure to complete follow-up and 3927 patients were analysed. IH was
diagnosed in 318 patients. The estimated incidence rates for IH were 5.2 per cent
at 12 months and 10.3 per cent at 24 months. In multivariable analysis, wound
classification III and IV (hazard ratio (HR) 2.26, 95 per cent confidence
interval 1.52 to 3.35), body mass index of 25 kg/m(2) or higher (HR 1.76, 1.35 to
2.30), midline incision (HR 1.74, 1.28 to 2.38), incisional surgical-site
infection (I-SSI) (HR 1.68, 1.24 to 2.28), preoperative chemotherapy (HR 1.61,
1.08 to 2.37), blood transfusion (HR 1.46, 1.04 to 2.05), increasing age by 10
year interval (HR 1.30, 1.16 to 1.45), female sex (HR 1.26, 1.01 to 1.59) and
thickness of subcutaneous tissue for every 1-cm increase (HR 1.18, 1.03 to 1.35)
were identified as independent risk factors. Compared with superficial I-SSI,
deep I-SSI was more strongly associated with the development of IH. CONCLUSION:
Although there are several risk factors for IH, reducing I-SSI is an important
step in the prevention of IH. REGISTRATION NUMBER: UMIN000004723 (University
Hospital Medical Information Network, http://www.umin.ac.jp/ctr/index.htm).
PMID- 25123380
TI - Mothering, fathering, and the regulation of negative and positive emotions in
high-functioning preschoolers with autism spectrum disorder.
AB - BACKGROUND: Children with autism spectrum disorder (ASD) exhibit difficulties in
regulating emotions and authors have called to study the specific processes
underpinning emotion regulation (ER) in ASD. Yet, little observational research
examined the strategies preschoolers with ASD use to regulate negative and
positive emotions in the presence of their mothers and fathers. METHODS: Forty
preschoolers with ASD and 40 matched typically developing children and their
mothers and fathers participated. Families were visited twice for identical
battery of paradigms with mother or father. Parent-child interactions were coded
for parent and child behaviors and children engaged in ER paradigms eliciting
negative (fear) and positive (joy) emotions with each parent. ER paradigms were
microcoded for negative and positive emotionality, ER strategies, and parent
regulation facilitation. RESULTS: During free play, mothers' and fathers'
sensitivity and warm discipline were comparable across groups; however, children
with ASD displayed lower positive engagement and higher withdrawal. During ER
paradigms, children with ASD expressed less positive emotionality overall and
more negative emotionality during fear with father. Children with ASD used more
simple self-regulatory strategies, particularly during fear, but expressed
comparable levels of assistance seeking behavior toward mother and father in
negative and positive contexts. Parents of children with ASD used less complex
regulation facilitation strategies, including cognitive reappraisal and emotional
reframing, and employed simple tactics, such as physical comforting to manage
fear and social gaze to maintain joy. CONCLUSION: Findings describe general and
parent- and emotion-specific processes of child ER and parent regulation
facilitation in preschoolers with ASD. Results underscore the ability of such
children to seek parental assistance during moments of high arousal and the
parents' sensitive adaptation to their children's needs. Reduced positive
emotionality, rather than increased negative reactivity and self-regulatory
efforts, emerges as the consistent element associated with ER processes in this
group.
PMID- 25123381
TI - Clinical evidence and bioinformatics characterization of potential hepatitis C
virus resistance pathways for sofosbuvir.
AB - Sofosbuvir (Sovaldi, SOF) is a nucleotide analog prodrug that targets the
hepatitis C virus (HCV) nonstructural protein 5B (NS5B) polymerase and inhibits
viral replication. High sustained virological response rates are achieved when
SOF is used in combination with ribavirin with or without pegylated interferon in
subjects with chronic HCV infection. Potential mechanisms of HCV resistance to
SOF and other nucleos(t)ide analog NS5B polymerase inhibitors are not well
understood. SOF was the first U.S. Food and Drug Administration (FDA)-approved
antiviral drug for which genotypic resistance analyses were based almost entirely
on next-generation sequencing (NGS), an emerging technology that lacks a standard
data analysis pipeline. The FDA Division of Antiviral Products developed an NGS
analysis pipeline and performed independent analyses of NGS data from five SOF
clinical trials. Additionally, structural bioinformatics approaches were used to
characterize potential resistance-associated substitutions. Using protocols we
developed, independent analyses of the NGS data reproduced results that were
comparable to those reported by Gilead Sciences, Inc. Low-frequency, treatment
emergent substitutions occurring at conserved NS5B amino acid positions in
subjects who experienced virological failure were also noted and further
evaluated. The NS5B substitutions, L159F (sometimes in combination with L320F or
C316N) and V321A, emerged in 2.2%-4.4% of subjects who failed SOF treatment
across clinical trials. Moreover, baseline polymorphisms at position 316 were
potentially associated with reduced response rates in HCV genotype 1b subjects.
Analyses of these variants modeled in NS5B crystal structures indicated that all
four substitutions could feasibly affect SOF anti-HCV activity. CONCLUSION: SOF
has a high barrier to resistance; however, low-frequency NS5B substitutions
associated with treatment failure were identified that may contribute to
resistance of this important drug for chronic HCV infection.
PMID- 25123382
TI - A comparison of airway dimensions, measured by acoustic reflectometry and
ultrasound before and after general anaesthesia.
AB - Changes in airway dimensions can occur during general anaesthesia and surgery for
a variety of reasons. This study explored factors associated with postoperative
changes in airway dimensions. Patient airway volume was measured by acoustic
reflectometory and neck muscle diameter by ultrasound echography in the pre- and
post-anaesthetic periods in a total of 281 patients. Neck circumference was also
assessed during these periods. A significant decrease in median (IQR [range])
total airway volume (from 63.8 (51.8-75.7 [14.7-103]) ml to 45.9 (33.5-57.2 [6.4
96.3]) ml, p < 0.0001), and a significant increase in muscle diameter (from 4.3
(3.3-5.6 [2.2-9.0]) mm to 5.8 (4.7-7.3 [2.8-1.3]) mm, p < 0.0001) and neck
circumference (from 34.0 (32.5-37.0 [29.5-49.0]) cm to 35.0 (33.5-38.0 [30.5
50.5]) cm, p < 0.0001) were observed. It may be possible that changes in airway
volume and neck circumference were influenced by surgical duration or peri
operative fluid management (rho) = -0.31 (95% CI -0.24 to -0.01), p = 0.0301,
0.17 (-0.23 to -0.06), p = 0.0038, 0.23 (0.12-0.34), p < 0.0001, and 0.16 (0.05
0.27), p = 0.0062, respectively). The intra-oral space can significantly decrease
and neck thickness increase after general anaesthesia, and might increase the
risk of difficult laryngoscopy and intubation if airway management is required
after extubation following general anaesthesia.
PMID- 25123384
TI - Editorial: Ultra violet (UV) exposure and IBD--should more be done to demonstrate
an association before trying to find its mechanism?
PMID- 25123383
TI - Editorial: Early corticosteroids in ulcerative colitis.
PMID- 25123385
TI - Editorial: Early corticosteroids in ulcerative colitis--authors' reply.
PMID- 25123386
TI - Editorial: UV exposure and IBD--should more be done to demonstrate an association
before trying to find its mechanism? Authors' reply.
PMID- 25123387
TI - Editorial: Escalation to weekly dosing in adalimumab-treated patients with active
ulcerative colitis.
PMID- 25123388
TI - Editorial: Unsedated transnasal endoscopy.
PMID- 25123389
TI - Editorial: Metabolomic analysis of breath volatile organic compounds--a new scent
for inflammatory bowel disease.
PMID- 25123390
TI - Editorial: Gut microbiota and chemotherapy- or radiation-induced gastrointestinal
mucositis.
PMID- 25123391
TI - Letter: Bismuth quadruple therapy with Pylera for H. pylori infection.
PMID- 25123392
TI - Letter: Bismuth quadruple therapy with Pylera for Helicobacter pylori infection-
authors' reply.
PMID- 25123393
TI - Letter: Herbal hepatotoxicity--an update on traditional Chinese medicine
preparations.
PMID- 25123394
TI - Letter: Herbal hepatotoxicity--an update on traditional Chinese medicine
preparations; authors' reply.
PMID- 25123396
TI - Binding of fullerenes to amyloid beta fibrils: size matters.
AB - Binding affinity of fullerenes C20, C36, C60, C70 and C84 for amyloid beta
fibrils is studied by docking and all-atom molecular dynamics simulations with
the Amber force field and water model TIP3P. Using the molecular mechanic-Poisson
Boltzmann surface area method one can demonstrate that the binding free energy
linearly decreases with the number of carbon atoms of fullerene, i.e. the larger
is the fullerene size, the higher is the binding affinity. Overall, fullerenes
bind to Abeta9-40 fibrils stronger than to Abeta17-42. The number of water
molecules trapped in the interior of 12Abeta9-40 fibrils was found to be lower
than inside pentamer 5Abeta17-42. C60 destroys Abeta17-42 fibril structure to a
greater extent compared to other fullerenes. Our study revealed that the van der
Waals interaction dominates over the electrostatic interaction and non-polar
residues of amyloid beta peptides play the significant role in interaction with
fullerenes providing novel insight into the development of drug candidates
against Alzheimer's disease.
PMID- 25123395
TI - Validation of DNA promoter hypermethylation biomarkers in breast cancer--a short
report.
AB - PURPOSE: DNA promoter hypermethylation of tumor suppressor genes is known to
occur early in cancer development, including breast cancer. To improve early
breast cancer detection, we aimed to investigate whether the identification of
DNA promoter hypermethylation might be of added value. METHODS: The methylation
status of a panel of 19 candidate genes (AKR1B1, ALX1, ARHGEF7, FZD10, GHSR,
GPX7, GREM1, GSTP1, HOXD1, KL, LHX2, MAL, MGMT, NDRG2, RASGRF2, SFRP1, SFRP2,
TM6SF1 and TMEFF2) was determined in formalin-fixed paraffin-embedded normal
breast and breast cancer tissue samples using gel-based methylation-specific PCR
(MSP). RESULTS: The promoters of the AKR1B1, ALX1, GHSR, GREM1, RASGRF2, SFRP2,
TM6SF1 and TMEFF2 genes were found to be significantly differentially methylated
in normal versus malignant breast tissues. Based on sensitivity, specificity and
logistic regression analyses the best performing genes for detecting breast
cancer were identified. Through multivariate analyses, we found that AKR1B1 and
TM6SF1 could detect breast cancer with an area under the curve (AUC) of 0.986 in
a receiver operating characteristic (ROC) assessment. CONCLUSIONS: Based on our
data, we conclude that AKR1B1 and TM6SF1 may serve as candidate methylation
biomarkers for early breast cancer detection. Further studies are underway to
evaluate the methylation status of these genes in body fluids, including nipple
aspirates and blood.
PMID- 25123398
TI - Activator-free palladium-catalyzed silylation of aryl chlorides with
silylsilatranes.
AB - The palladium-catalyzed silylation of aryl chlorides with silylsilatranes
proceeds under activator-free conditions; hence, wide functional group
compatibility is displayed and boryl and siloxy groups are able to survive.
Experimental and computational studies revealed that smooth transmetalation from
the silylsilatrane to the arylpalladium chloride is facilitated by strong
interaction between the Lewis acidic silicon and the chloride.
PMID- 25123397
TI - Profilin as a severe food allergen in allergic patients overexposed to grass
pollen.
AB - BACKGROUND: Profilins are ubiquitous proteins that act as panallergens in
sensitized patients, considered to be mild or incomplete food allergens. The aim
of the study was to evaluate the role of profilins as severe food allergens in
allergic patients overexposed to grass who were referred for severe food
reactions and were sensitized to profilins. METHODS: After a careful in vitro
screening, 26 patients were included, classified into two groups, mild (17) and
severe reactors (9), based on clinical history and subsequently provoked orally
with purified profilin in a double-blind placebo-controlled food challenge setup.
RESULTS: A significant number of patients presented severe positive food
challenge test reactions at low doses of the allergen profilin. Patients prone to
suffer from severe reactions had lower IgG4/IgE ratio to major grass allergens
than those who did not. CONCLUSION: Profilins are complete food allergens in food
allergic patient populations that are exposed to high levels of grass pollen.
This type of patient constitutes an optimal model to understand the link between
respiratory and food allergies. The nature of the observed reactions and the low
level of allergen eliciting the reactions suggest that intake through the oral
mucosa might constitute a relevant route of exposure to food allergens.
PMID- 25123399
TI - Triphenylamine groups improve blocking behavior of phenoxazine dyes in cobalt
electrolyte-based dye-sensitized solar cells.
AB - Novel phenoxazine dyes are successfully introduced as sensitizers into dye
sensitized solar cells (DSCs) with cobalt-based electrolyte. In sensitizers with
triphenylamine (TPA) groups recombination from electrons in the TiO2 conduction
band to the cobalt(III) species is suppressed. The effect of the steric
properties of the phenoxazine sensitizers on the overall device performance and
on recombination and regeneration processes is compared. Optimized DSCs
sensitized with IB2 having two TPA groups in combination with tris(2,2'
bipyridyl) cobalt(II/III) yield efficiencies of 6.3%, similar to that of IB3,
which is equipped with mutiple alkoxy groups. TH310 with only one TPA group gives
lower efficiency and open circuit voltage, while IB1 without TPA groups performs
even worse. These results demonstrate that both TPA groups on the IB2 are needed
for an efficient blocking effect. These results reveal a possible new role for
TPA units in DSC sensitizer design.
PMID- 25123400
TI - Stage-specific metabolization of triacylglycerols during seed germination of
Sacha Inchi (Plukenetia volubilis L.).
AB - BACKGROUND: A detailed study was carried out on Sacha Inchi (Plukenetia volubilis
L.) to investigate the mobilization of storage lipids during seed germination.
RESULTS: Thin layer chromatography analysis of the total lipids showed a rapid
decline in the triacylglycerol (TAG) and diacylglycerol (DAG) contents after the
early stages (3-10 days after imbibition (DAI)) followed by a steady breakdown
during the later stages (20 and 30 DAI) of germination. Trace amounts of
monoacylglycerols (MAG) were identified during the final stage (30 DAI). Further,
gas chromatography analysis showed an increase in the major unsaturated fatty
acid (linoleic and linolenic) content from 3 to 10 DAI followed by a slow
decline. In addition, the major saturated fatty acid (palmitic and oleic) content
showed a decrease during the early stages (3-10 DAI) and an increase during the
later stages (20 and 30 DAI). CONCLUSION: The present study provides the first
report on the metabolization of TAG along with fatty acid changes during the seed
germination of Sacha Inchi.
PMID- 25123401
TI - Blue SHG enhancement by silver nanocubes photochemically prepared on a RbTiOPO4
ferroelectric crystal.
AB - Silver nanocubes with low size dispersion have been selectively photo-deposited
on the positive surface of a periodically poled RbTiOPO4 ferroelectric crystal.
The obtained nanocubes show preferential orientations with respect to the
substrate suggesting epitaxial growth. The plasmonic resonances supported by the
nanocubes are exploited to enhance blue SHG at the domain walls.
PMID- 25123402
TI - Improving paediatric diabetes care with the use of an integrated paediatric
electronic diabetes information management system and routine uploading of blood
glucose meters and insulin pumps in outpatient clinics.
PMID- 25123403
TI - Why is kernicterus still a major cause of death and disability in low-income and
middle-income countries?
AB - Neonatal jaundice is predominantly a benign condition that affects 60%-80% of
newborns worldwide but progresses to potentially harmful severe
hyperbilirubinaemia in some. Despite the proven therapeutic benefits of
phototherapy for preventing extreme hyperbilirubinaemia, acute bilirubin
encephalopathy or kernicterus, several low-income and middle-income countries
(LMIC) continue to report high rates of avoidable exchange transfusions, as well
as bilirubin-induced mortality and neurodevelopmental disorders. Considering the
critical role of appropriate timing in treatment effectiveness, this review set
out to examine the contributory factors to the burden of severe
hyperbilirubinaemia and kernicterus based on the 'three delays model' described
by Thaddeus and Maine in the 91 most economically disadvantaged LMICs with Gross
National Income per capita <=US$6000 and median human development index of 0.525
(IQR: 0.436-0.632). Strategies for addressing these delays are proposed including
the need for clinical and public health leadership to curtail the risk and burden
of kernicterus in LMICs.
PMID- 25123404
TI - Propranolol for infantile haemangiomas: single centre experience of 250 cases and
proposed therapeutic protocol.
AB - OBJECTIVE: To assess the safety and efficacy of systemic propranolol for the
treatment of complicated infantile haemangiomas. DESIGN: Retrospective review of
case notes of paediatric patients treated with propranolol for complicated
infantile haemangiomas. SETTING: Tertiary care children's hospital. PATIENTS: All
paediatric patients with complicated infantile haemangiomas who commenced
treatment with propranolol from July 2008 to December 2011 and have completed
treatment for at least 3 months. RESULTS: 250 patients were treated with
propranolol; 34.4% were premature and 5.6% postmature. Indications for
propranolol included: vision compromise (42.0%), bleeding and/or ulceration
(30.4%) airway obstruction (8.8%), feeding difficulty (8.4%), risk of permanent
disfigurement (4.4%) and other (6%) (nasal obstruction, auditory canal
obstruction, large haemangioma, compression of neck structure and spinal cord).
Median age at beginning of treatment was 4.5 months. Median age at end of
treatment was 16.7 months. Median length of therapy was 11.8 months. Adverse
effects (such as wheezing, worsening of ulceration, sleep disturbance, diarrhoea)
occurred in 38 patients (15.2%), leading to modifications in management in 26
patients (10.4%). 240 patients (96%) had good to excellent response to treatment.
20 patients (8%) experienced regrowth of the haemangioma on cessation of
propranolol and six patients (2.4%) required propranolol to be restarted.
CONCLUSIONS: In appropriately selected patients, propranolol is a safe and
effective treatment for infantile haemangiomas.
PMID- 25123406
TI - Preparation of dithienylphospholes by 1,1-carboboration.
AB - In this study the scope of the 1,1-carboboration reaction was extended to the
preparation of mixed heterole-based conjugated pi-systems. Two
arylbis(alkynyl)phosphane starting materials 2 were synthesized bearing two
thiophene isomers at the alkyne units and the bulky tipp-substituent (tipp=2,4,6
triisopropylphenyl) at the phosphorous atom. The bis(thienylethynyl)phosphanes 2
were converted into the corresponding 2,5-thienyl-substituted 3-borylphospholes 4
in a double 1,1-carboboration reaction sequence employing the strongly
electrophilic B(C6 F5 )3 reagent under mild reaction conditions. Subsequent
Suzuki-Miyaura type cross-coupling yielded the corresponding 3-phenylphospholes 7
in a one-pot procedure from phosphanes 2 in high yields. Phospholes 7 were
converted into the respective phosphole oxides 8. A photophysical
characterization of derivatives 7 and 8 was carried out. The results presented
here demonstrate the suitability of the 1,1-carboboration reaction for the
preparation of phosphole-/thiophene-based, light-emitting systems.
PMID- 25123405
TI - Successful outcome of renal transplantation in a child with HIV-associated
nephropathy.
AB - Classical HIV-associated nephropathy (HIVAN) was first described before the
advent of highly active antiretroviral therapy in late stages of HIV disease with
high viral load and low CD4 cell count. Renal transplantation has been successful
in a large series of carefully selected HIV-infected adults, with patient and
renal allograft survival approaching those of non-HIV-infected patients. We
report the successful outcome of living related renal transplantation in a
vertically transmitted HIV-infected 8-year-old girl with end-stage kidney disease
on haemodialysis due to HIVAN. The pretransplant preparations and post-transplant
care, with particular emphasis on immunosuppression and avoidance of
opportunistic infections, are discussed.
PMID- 25123407
TI - Fullerene growth from encapsulated graphene flakes.
AB - The direct in situ observation of fullerene formation encapsulated within a
graphene ridge has been made possible using an aberration corrected transmission
electron microscope (AC-TEM). An atom-by-atom mechanism was proposed based on in
situ AC-TEM observations. First principle calculations found a continuous energy
decrease upon the addition of carbon atoms to the edge of the graphene flakes,
which mimics the fullerene growth steps and supports the atom-by-atom mechanism.
The ridged graphene structure worked as a container for pinning small graphene
flakes and capturing carbon atoms, which increased the growth probability of the
fullerene structure within the small encapsulated space.
PMID- 25123408
TI - Genomic medicine: a question of value: despite the promise of personalized
medicine, genomic testing has yet to prove its cost-effectiveness.
PMID- 25123409
TI - Complications related to harvest of the proximal end of the fibula: a systematic
review.
AB - BACKGROUND: The fibula is a common source of bone graft used in skeletal
reconstruction. Although in most cases only the diaphysis of the fibula is used,
there are clinical scenarios in which the proximal end of the fibula and fibular
head are harvested for use in articular reconstruction. The purpose of this
systematic review is to determine the incidence of knee instability and peroneal
nerve motor dysfunction associated with removal of the proximal end of the fibula
and fibular head. METHODS: A systematic search was performed using the PubMed,
Ovid MEDLINE, and cochrane databases. Studies accepted for review included those
that clearly reported donor site morbidity (instability or peroneal nerve motor
dysfunction) after proximal fibula resection. All studies in which the proximal
fibula was resected for bone graft or for marginal resection of tumor were
included. RESULTS: Fifteen studies reporting a total of 337 patients were
included. The rate of symptomatic knee instability after proximal fibula
resection was 3.9%. The incidence of instability that was detectible on physical
examination or stress radiographs was higher. Although transient motor
dysfunction was not uncommon, the incidence of persistent peroneal nerve motor
dysfunction was 2.6%. CONCLUSION: Although asymptomatic laxity is common, the
incidence of symptomatic knee instability after resection of the proximal fibula
is relatively low. The incidence of persistent peroneal nerve motor dysfunction
is also low when the nerve is intentionally protected during surgery.
PMID- 25123410
TI - A national study on adherence to a basal cell carcinoma guideline; development of
a tool to assess guideline adherence.
AB - BACKGROUND: Clinical practice guideline implementation may be at variance with
actual daily practice, as guideline adherence is a complex process depending on
many actors and factors. Feedback regarding adherence is essential to monitor the
effect that a guideline has in clinical practice and whether or not the quality
of care is raised by implementation. OBJECTIVES: Developing a tool for obtaining
and giving nationwide feedback regarding adherence. METHODS: From February 2010
to June 2013, a 32-item questionnaire was used as an audit tool during committee
visits to assess adherence across 37 dermatological centres in The Netherlands.
The questions were derived from the recommendations by the Dutch Dermatological
and Venereological Society (NVDV) in the Dutch Basal Cell Carcinoma (BCC)
guideline. Five selected medical records per dermatologist were audited and the
results were discussed with the audited centre. Data were pooled to calculate the
compliance with each recommendation across all participating centres. RESULTS:
Adherence to recommended actions varied considerably (20.2-100%) across the
domains of prevention, diagnostics, treatments and aftercare. Using and reporting
surgical margins, giving patient advice, restricting the use of cryosurgery for
certain BCCs and reporting on prognostic factors all failed to reach a threshold
of 80%. Nonadherence to recommended actions proved to be related to whether or
not a dermatologist was directly involved. CONCLUSIONS: The findings emphasize
the importance of direct feedback to practitioners regarding adherence.
Furthermore, together with existing frameworks, the method described could be
used by developers in a guideline update to identify and anticipate barriers to
successful implementation.
PMID- 25123411
TI - Simultaneous flow cytometric analysis of IFN-gamma and CD4 mRNA and protein
expression kinetics in human peripheral blood mononuclear cells during
activation.
AB - The application of fluorescently-labeled antibodies for flow cytometric
identification and characterization of specific cell types within heterogeneous
populations by their protein expression profile is well established. While
detection of proteins is informative, concomitant transcript analysis in the same
cells would provide a more complete and comprehensive view of intracellular
signaling events. We recently reported on the efficient detection of RNA in
suspension cells for flow cytometric analysis. The improved RNA flow cytometry
procedure described here allows for the specific labeling of multiple RNA
species, and is compatible with antibody-based targeting of extracellular and
intracellular antigens for multiplexing purposes. To show proof of concept, human
peripheral blood mononuclear cells were stimulated with phorbol 12-myristate 13
acetate and ionomycin for a maximum of 5 h, during which their CD4 and interferon
gamma (IFN-gamma) transcript and protein levels were monitored. Substantial and
increasing numbers of IFN-gamma mRNA+ cells were detected within 30 min after
initiation of induction, while IFN-gamma protein+ cells could only be discerned
at 1 h and beyond. Surprisingly, resting lymphocytes contained less CD4 mRNA but
more of the protein per cell compared with monocytes, revealing a difference in
the relationship of transcript and protein levels in these two cell types. We
additionally applied monensin, which is commonly used to block cytokine
secretion, and found that IFN-gamma mRNA can still be analyzed consistently using
the improved RNA flow cytometry staining method. Notably, a subset of IFN-gamma
mRNA(-)/protein+ cells that were not observed in the absence of monensin became
apparent at the 5-h mark. This subset probably represents cells that have
accumulated IFN-gamma protein, but no longer transcribe mRNA. Collectively, the
results described here exemplify how the improved RNA flow cytometry labeling
procedure can be applied to simultaneously assess mRNA and protein dynamics to
gain insight into the regulation of gene transcription and translation in
individual cells.
PMID- 25123412
TI - Screening for prostate cancer in the US? Reduce the harms and keep the benefit.
AB - While the benefit of prostate-specific antigen (PSA) based screening is
uncertain, a significant proportion of screen-detected cases is overdiagnosed. In
order to make screening worthwhile, it is necessary to find policies that
minimize overdiagnosis, without significantly increasing prostate cancer
mortality (PCM). Using a microsimulation model (MISCAN) we project the outcomes
of 83 screening policies in the US population, with different start and stop
ages, screening frequencies, strategies where the PSA value changes the screening
frequency, and strategies in which the PSA threshold (PSAt) increases with age.
In the basecase strategy, yearly screening 50-74 with a PSAt of 3, the lifetime
risk of PCM and overdiagnosis equals, respectively, 2.4 and 3.8%. The policies
that reduce overdiagnosis the most (for maximum PCM increases relative to
basecase of 1%, 3%, and 5%, respectively) are with a PSAt of 3, (1) yearly
screening 50-74 where, if PSA <1 at age 65 or older, frequency becomes 4 years,
with 3.6% (5.9% reduction), (2) 2-year screening 50-72, with 2.9% (24.3%
reduction), and (3) yearly screening 50-70 (PSAt of 4 after age 66), with 2.2%
(43.4% reduction). Stopping screening at age 70 is a reasonable way to reduce the
harms and keep the benefit. Decreasing the stopping age has a larger effect on
overdiagnosis reduction than reducing the screen frequency. Screening policies
where the frequency of screening depends on PSA result or in which the PSAt
changes with age did not substantially improve the balance of harms and benefits
relative to simple yearly screening.
PMID- 25123413
TI - Effect of physicochemical factors on glycerol production by simultaneous cultures
of wine micro-organisms using the response surface method.
AB - AIM: To evaluate the effect of temperature, pH and SO2 on growth and glycerol
production improvement by Saccharomyces cerevisiae mc2, Kloeckera apiculata mF
and Oenococcus oeni X2L using the response surface method (RSM). METHODS AND
RESULTS: Multifactorial design of cultures with physicochemical factors
variations was performed. The micro-organisms grew in all cultures conditions.
Overall, after 6 days yeasts prevailed, especially S. cerevisiae (10(9) CFU ml(
1)), while O. oeni reached 10(7) CFU ml(-1). At initial fixed pH 5.5, metabolic
behaviour of cultures showed a temperature-dependent response. Total malate
consumption occurred at 26 degrees C, 50 mg l(-1) SO2. Glucose and pentoses
utilization was highly modified when varying SO2. Ethanol showed negative
interaction with temperature-SO2 relationship. At low SO2, glycerol and acetate
production increased when temperature enhanced. Predictive results of RSM
indicate that 26 degrees C, 60.24 mg l(-1) SO2 and pH 5.5 were the optimal
conditions for glycerol and organic acids synthesis compatible with wine quality.
CONCLUSIONS: We propose a predictive condition to improve the performance of
mixed cultures for must fermentations. SIGNIFICANCE AND IMPACT OF THE STUDY: To
optimize the culture conditions to design mixed starters containing autochthonous
yeasts and O. oeni strains for winemaking and to obtain products with high
glycerol content, low acidity and maintenance of regional characteristics.
PMID- 25123414
TI - Sub-crestal positioning of implants results in higher bony crest resorption: an
experimental study in dogs.
AB - OBJECTIVE: To compare peri-implant soft- and hard-tissue integration at implants
installed juxta- or sub-crestally. Furthermore, differences in the hard and soft
peri-implant tissue dimensions at sites prepared with drills or sonic instruments
were to be evaluated. MATERIAL AND METHODS: Three months after tooth extraction
in six dogs, recipient sites were prepared in both sides of the mandible using
conventional drills or a sonic device (Sonosurgery((r))). Two implants with a 1.7
mm high-polished neck were installed, one with the rough/smooth surface interface
placed at the level of the buccal bony crest (control) and the second placed 1.3
mm deeper (test). After 8 weeks of non-submerged healing, biopsies were harvested
and ground sections prepared for histological evaluation. RESULTS: The buccal
distances between the abutment/fixture junction (AF) and the most coronal level
of osseointegration (B) were 1.6 +/- 0.6 and 2.4 +/- 0.4 mm; between AF and the
top of the bony crest (C), they were 1.4 +/- 0.4 and 2.2 +/- 0.2 mm at the test
and control sites, respectively. The top of the peri-implant mucosa (PM) was
located more coronally at the test (1.2 +/- 0.6 mm) compared to the control sites
(0.6 +/- 0.5 mm). However, when the original position of the bony crest was taken
into account, a higher bone loss and a more apical position of the peri-implant
mucosa resulted at the test sites. CONCLUSIONS: The placement of implants into a
sub-crestal location resulted in a higher vertical buccal bone resorption and a
more apical position of the peri-implant mucosa in relation to the level of the
bony crest at implant installation. Moreover, peri-implant hard-tissue dimensions
were similar at sites prepared with either drills or Sonosurgery((r)).
PMID- 25123415
TI - Mosaic activity patterns and their relation to perceptual similarity: open
discussions on the molecular basis and circuitry of odor recognition.
AB - Enormous advances have been made in the recent years in regard to the mechanisms
and neural circuits by which odors are sensed and perceived. Part of this
understanding has been gained from parallel studies in insects and rodents that
show striking similarity in the mechanisms they use to sense, encode, and
perceive odors. In this review, we provide a short introduction to the
functioning of olfactory systems from transduction of odorant stimuli into
electrical signals in sensory neurons to the anatomical and functional
organization of the networks involved in neural representation of odors in the
central nervous system. We make emphasis on the functional and anatomical
architecture of the first synaptic relay of the olfactory circuit, the olfactory
bulb in vertebrates and the antennal lobe in insects. We discuss how the
exquisite and conserved architecture of this structure is established and how
different odors are encoded in mosaic activity patterns. Finally, we discuss the
validity of methods used to compare activation patterns in relation to perceptual
similarity.
PMID- 25123417
TI - Epidemiological research on the incidence and prevalence of arterial hypertension
in the Portuguese population: a scoping review.
AB - INTRODUCTION AND OBJECTIVES: The Portuguese population is reported to have among
the highest levels of mean blood pressure. The aim of the present study is to
conduct a structured literature review describing the scope (quantity, focus and
nature) of published epidemiological research on the prevalence and incidence of
hypertension in the Portuguese population. METHODS: The scoping review was
conducted during June 2013, using two information sources, B-on and PubMed, to
search for published studies on the prevalence and incidence of hypertension with
data collected between 2005-2013 and 1995-2013, respectively. RESULTS: We
identified 527 publications: 14 on the prevalence and two on the incidence of
hypertension. The results show more studies on populations in the North region of
Portugal; an apparent lack of published studies specifically targeting the
Alentejo and Algarve populations; long delays between data collection and
publication of results (up to nine years); considerable variability in
measurement methods; and infrequent data stratification by gender and age.
CONCLUSIONS: Differences in blood pressure measurement methods, not specified in
most studies, the infrequency of stratification of results by gender and age, and
the geographic asymmetry in coverage of the Portuguese population, hinder
monitoring of the incidence and prevalence of hypertension in Portugal.
PMID- 25123416
TI - Synthesis and evaluation of translocator 18 kDa protein (TSPO) positron emission
tomography (PET) radioligands with low binding sensitivity to human single
nucleotide polymorphism rs6971.
AB - The imaging of translocator 18 kDa protein (TSPO) in living human brain with
radioligands by positron emission tomography (PET) has become an important means
for the study of neuroinflammatory conditions occurring in several
neuropsychiatric disorders. The widely used prototypical PET radioligand
[(11)C](R)-PK 11195 ([(11)C](R)-1; [N-methyl-(11)C](R)-N-sec-butyl-1-(2
chlorophenyl)-N-methylisoquinoline-3-carboxamide) gives a low PET signal and is
difficult to quantify, whereas later generation radioligands have binding
sensitivity to a human single nucleotide polymorphism (SNP) rs6971, which imposes
limitations on their utility for comparative quantitative PET studies of normal
and diseased subjects. Recently, azaisosteres of 1 have been developed with
improved drug-like properties, including enhanced TSPO affinity accompanied by
moderated lipophilicity. Here we selected three of these new ligands (7-9) for
labeling with carbon-11 and for evaluation in monkey as candidate PET
radioligands for imaging brain TSPO. Each radioligand was readily prepared by
(11)C-methylation of an N-desmethyl precursor and was found to give a high
proportion of TSPO-specific binding in monkey brain. One of these radioligands,
[(11)C]7, the direct 4-azaisostere of 1, presents many radioligand properties
that are superior to those reported for [(11)C]1, including higher affinity,
lower lipophilicity, and stable quantifiable PET signal. Importantly, 7 was also
found to show very low sensitivity to the human SNP rs6971 in vitro. Therefore,
[(11)C]7 now warrants evaluation in human subjects with PET to assess its utility
for imaging TSPO in human brain, irrespective of subject genotype.
PMID- 25123418
TI - Staff's person-centredness in dementia care in relation to job characteristics
and job-related well-being: a cross-sectional survey in nursing homes.
AB - AIM: To explore the role of nursing staff's person-centredness caring for people
with dementia in relation to their work environment and job-related well-being.
BACKGROUND: Given the development towards person-centred care and labour force
issues, research has recently focused on the effect of person-centredness on
nursing staff's well-being. Findings from occupational stress research suggest
that employees' personal characteristics, such as person-centredness, can
moderate the impact particular job characteristics have on their job-related well
being. DESIGN: Cross-sectional survey. METHODS: A national survey was conducted
among healthcare staff (n = 1147) in 136 living arrangements for people with
dementia in the Netherlands (2008-2009). Hierarchical regression analyses were
used. RESULTS: Person-centredness moderates the relationship between coworker
support and three outcomes of job-related well-being and between supervisor
support and two of these outcomes. For highly person-centred nursing staff,
coworker support was found to have a weaker impact and supervisor support to have
a stronger impact on their job-related well-being. In addition, direct effects
showed that person-centredness was weakly associated with more job satisfaction,
more emotional exhaustion and more strongly with more personal accomplishment.
CONCLUSION: Nursing staff's person-centredness does play a modest role in
relation to job characteristics and job-related well-being. Findings indicate
that person-centredness is not only beneficial to residents with dementia as
found earlier, but also for nursing staff themselves; specifically, in case
nursing staff members feel supported by their supervisor. Since a more person
centred workforce feels more competent, further implementation of person-centred
care might have a positive impact on the attractiveness of the profession.
PMID- 25123419
TI - Pilomatricoma of the male breast: sonographic mammographic MRI features with
pathologic correlation.
AB - We report a case of 43-year-old man who presented with an enlarging, painless,
palpable mass in the left breast for one year associated with surface blue
discoloration of the skin. Mammogram showed a well-defined 2.3-cm mass with
microcalcifications. Ultrasound revealed a well-defined, subcutaneous hypoechoic
mass adherent to the skin with multiple bright foci. Ultrasound-guided needle
biopsy produced a dark-colored sample corresponding to pilomatricoma on final
pathology. Bilateral breast magnetic resonance imaging showed heterogeneously
hyperintense in T1- and T2-weighted images with heterogeneous enhancement toward
the delayed phase. Surgical resection was carried out with wide margins.
PMID- 25123420
TI - Retro-ureteral internal hernia after transperitoneal ureter reimplantation: an
unusual cause of small bowel obstruction.
AB - Report of a case of surgically confirmed closed-loop small bowel obstruction due
to internal hernia following transperitoneal ureter reimplantation. Multidetector
computed tomography (CT) demonstrated the presence and the cause of this unusual
postsurgical internal hernia. The CT findings are presented herein.
PMID- 25123421
TI - Chronic recurrent multifocal osteomyelitis complicated by hip subluxation: a case
report.
PMID- 25123422
TI - Cytological follow-up after hysterectomy: is vaginal vault cytology sampling a
clinical governance problem? The University Hospital of North Staffordshire
approach.
AB - OBJECTIVES: Vaginal vault cytology sampling following hysterectomy is recommended
for specific indications in national guidelines. However, clinical governance
issues surround compliance with guidance. Our first study objective was to
quantify how many patients undergoing hysterectomy at the University Hospital of
North Staffordshire (UHNS) had vault cytology advice in their histology report
and, if indicated, whether it was arranged. The second was to devise a vault
cytology protocol based on local experience and national guidance. METHODS: The
local cancer registry was searched. Clinical, clerical and histological data for
all patients undergoing hysterectomy were collected. RESULTS: In total, 271
patients were identified from both the gynae-oncology and benign gynaecology
teams. Of these, 24% (65/271) were gynae-oncology patients with a mean age of 69
years. The benign gynaecology team had 76% (206/271) of patients with a mean age
of 55 years. Subsequently, 94% (256/271) had cytology follow-up advice in their
histopathology report. Ultimately, from both cohorts, 39% (18/46) had follow-up
cytology performed when indicated. CONCLUSION: A high proportion of cases
complied with national guidance. However, a disappointingly high number did not
have vault cytology sampling when this was indicated. This is probably a result
of the complex guidance that is misunderstood in both primary and secondary care.
Vault follow-up of patients after hysterectomy rests with the team performing the
surgery. Vault cytology, if indicated, should be performed in secondary care and
follow-up should be planned. The protocol set out in this article should be
followed to avoid unnecessary clinical governance failings.
PMID- 25123423
TI - Sulphate fertilization ameliorates long-term aluminum toxicity symptoms in
perennial ryegrass (Lolium perenne).
AB - Effects of the oxanion sulphate on plant aluminum (Al(3+)) detoxification
mechanisms are not well understood. Therefore, holistic physiological and
biochemical modifications induced by progressively increased doses of sulphate
fertilization in the presence of long-term Al(3+) stress were investigated in the
aluminum sensitive perennial ryegrass (Lolium perenne L. cvJumbo). Plant growth
inhibition induced by Al(3+) was decreased in response to increasing doses of
sulphate supply. Aluminum concentrations measured in roots of perennial ryegrass
by atomic absorption spectrometry declined significantly with increasing sulphate
concentrations. In parallel, we determined a rise of sulphur in shoots and roots
of perennial ryegrass. Inclusion of up to 360 MUM of sulphate enhanced cysteine
and glutathione biosynthesis in Al(3+) (1.07 MUM) treated plants. This increase
of thiol-containing compounds favored all modifications in the glutathione redox
balance, declining lipid peroxidation, decreasing the activity of superoxide
dismutase, and modifying the expression of proteins involved in the diminution of
Al(3+) toxicity in roots. In particular, proteome analysis by 1D-SDS-PAGE and LC
MS/MS allowed to identify up (e.g. vacuolar proton ATPase, proteosome beta
subunit, etc) and down (Glyoxilase I, Ascorbate peroxidase, etc.) regulated
proteins induced by Al(3+) toxicity symptoms in roots. Although, sulphate supply
up to 480 MUM caused a reduction in Al(3+) toxicity symptoms, it was not as
efficient as compared to 360 MUM sulphate fertilization. These results suggest
that sulphate fertilization ameliorates Al(3+) toxicity responses in an
intracellular specific manner within Lolium perenne.
PMID- 25123424
TI - Delphi consensus on the current clinical and therapeutic knowledge on Anderson
Fabry disease.
AB - BACKGROUND: Management of Anderson-Fabry disease (AFD) is contentious,
particularly regarding enzyme replacement therapy (ERT). We report results of a
Delphi consensus panel on AFD management. METHODS: A survey to gauge consensus
among AFD experts was distributed online and responses were analysed. Statements
on: 1) diagnosis; 2) when starting ERT; 3) management of ERT infusion and adverse
reactions; and 4) follow-up/monitoring response to therapy and progression of
disease were included. Responses without consensus were discussed with an
enlarged panel and modified to reach consensus. RESULTS: 15 experts responded to
the survey. After plenary discussion among the enlarged panel, consensus was
reached on most statements. Key points were the use of a target organ biopsy to
show Gb3 deposits in symptomatic women with negative molecular analysis, the need
for ERT in symptomatic women and in all patients with persistent signs and
symptoms +/- organ damage. It was agreed to assess vital signs before ERT
administration and use a 0.2 MUL filter on infusion to reduce the risk of adverse
reactions, that serum should be drawn prior to the first infusion for anti
agalsidase antibody analysis to have a baseline value if a subsequent adverse
reaction appears, and that pre-medication is required in those with prior
infusion reactions. Holter ECG monitoring, cardiac and brain MRI, renal
parameters, and abdominal ultrasound were considered important for the assessment
of disease progression and response at ERT. CONCLUSIONS: This consensus supplies
guidance to healthcare providers on best practice in the management of patients
with AFD and indicates a need for more guidance.
PMID- 25123425
TI - Prevalence of malnutrition, obesity and nutritional risk of Australian paediatric
inpatients: a national one-day snapshot.
AB - AIM: Low prevalence rates of malnutrition at 2.5% to 4% have previously been
reported in two tertiary paediatric Australian hospitals. The current study is
the first to measure the prevalence of malnutrition, obesity and nutritional risk
of paediatric inpatients in multiple hospitals throughout Australia. METHODS:
Malnutrition, obesity and nutritional risk prevalence were investigated in 832
and 570 paediatric inpatients, respectively, in eight tertiary paediatric
hospitals and eight regional hospitals across Australia on a single day.
Malnutrition and obesity prevalence was determined using z-scores and body mass
index (BMI) percentiles. High nutritional risk was determined as a Paediatric
Yorkhill Malnutrition Score of 2 or more. RESULTS: The prevalence rates of
malnourished, wasted, stunted, overweight and obese paediatric patients were 15%,
13.8%, 11.9%, 8.8% and 9.9%, respectively. Patients who identified as Aboriginal
and Torres Strait Islander were more likely to have lower height-for-age z-scores
(P < 0.01); however, BMI and weight-for-age z-scores were not significantly
different. Children who were younger, from regional hospitals or with a primary
diagnosis of cardiac disease or cystic fibrosis had significantly lower
anthropometric z-scores (P = 0.05). Forty-four per cent of patients were
identified as at high nutritional risk and requiring further nutritional
assessment. CONCLUSIONS: The prevalence of malnutrition and nutritional risk of
Australian paediatric inpatients on a given day was much higher when compared
with the healthy population. In contrast, the proportion of overweight and obese
patients was less.
PMID- 25123426
TI - Cytotoxic effects of escin on human castration-resistant prostate cancer cells
through the induction of apoptosis and G2/M cell cycle arrest.
AB - OBJECTIVE: To evaluate the in vitro and in vivo effects of escin on human
castration-resistant prostate cancer (CRPC) cells, PC-3 and DU-145. MATERIALS AND
METHODS: The inhibition of cell proliferation and its mechanism were assessed
through a cytotoxicity assay, flow cytometry, and Western blot. The in vivo
efficacy of escin in CRPC cells was assessed using a xenograft tumor model
subcutaneously established in BALB/c nude mice. RESULTS: The treatment with escin
significantly reduced cell viability of CRPC cells in a dose- and time-dependent
manner. Escin induced apoptosis in a time-dependent manner, which was accompanied
by increases in pro-apoptotic (BCL-2 associated X protein, cleaved-caspase3, and
cleaved-poly [adenosine diphosphate-ribose] polymerase) proteins and decreases in
antiapoptotic (X-linked inhibitor of apoptosis protein, cellular inhibitor of
apoptosis protein-1, cellular inhibitor of apoptosis protein-2B-cell
leukemia/lymphoma-2, and B-cell lymphoma-extra large) proteins. Escin induced
G2/M-phase cell cycle arrest and thus led to a significant decrease in the
expression of cyclinB1 and its activating partner cyclin-dependent kinase 1, with
the concomitant induction of p21. In addition, escin significantly inhibited the
growth of CRPC cells in xenograft models. CONCLUSION: The results show that escin
induced cytotoxic effects on CRPC cells through the induction of apoptosis and
G2/M cell cycle arrest, indicating it may be a novel therapeutic agent for CRPC.
PMID- 25123427
TI - The antitumor effect of suicide gene therapy using Bifidobacterium infantis
mediated herpes simplex virus thymidine kinase/ganciclovir in a nude mice model
of renal cell carcinoma.
AB - OBJECTIVE: To confirm the effectivity of Bifidobacterium infantis-mediated herpes
simplex virus thymidine kinase/ganciclovir suicide gene system on the treatment
of renal cell carcinoma in nude mice and further explore the mechanisms.
MATERIALS AND METHODS: A B infantis thymidine kinase (B infantis-TK) suicide gene
system was constructed in our previous study. Tumor-bearing nude mice were
randomized into 4 groups and injected with normal saline, B infantis, B
infantis/pGEX-1lambdaT, and B infantis-TK, respectively, via tail vein, followed
by intraperitoneal injection of ganciclovir. The treatment effects were evaluated
by the terminal deoxynucleotidyl transferase-mediated deoxynucleotide
triphosphate nick end labeling assay, quantitative reverse transcriptase
polymerase chain reaction, and Western blotting. Side effects were also recorded.
RESULTS: Compared with the other 3 treatments, the treatment with B infantis-TK
resulted in a significant effective antitumor activity and stronger apoptotic
response. Western blot analysis showed that the expression levels of Rel A and
Bcl-xL were significantly lower, whereas those of caspase 3 and Bax were
significantly higher in tumor tissues resected from group B infantis-TK, which
were consistent with the quantitative reverse transcriptase-polymerase chain
reaction results. CONCLUSION: The B infantis-TK/ganciclovir therapy system
exhibits an effective antitumor activity by promoting tumor cell apoptosis
through both the intrinsic and the extrinsic apoptotic pathways.
PMID- 25123428
TI - Gossypiboma mimicking a retroperitoneal tumor.
AB - "Gossypiboma" denotes a mass of cotton that is retained in the body after
surgery. An image is presented of a retroperitoneal mass in a lady who had a
right nephrectomy 8 years earlier for a nonfunctioning kidney. Clinical
examination and plain abdominal radiography were not contributory. Contrast
enhanced abdominal computed tomography revealed a well-defined, heterogeneous,
spherical, soft-tissue mass, 13 * 9 * 9 cm in size, in the retroperitoneum, with
a dense enhanced wall, abutting the right psoas and posterior abdominal wall.
Exploration revealed an abdominal sponge surrounded by foreign body granuloma
adherent to surrounding structures. Gossypiboma can mimic a tumor and is a
diagnostic challenge.
PMID- 25123429
TI - Comparison of radiation dose from conventional and triple-bolus computed
tomography urography protocols in the diagnosis and management of patients with
renal cortical neoplasms.
AB - OBJECTIVE: To retrospectively compare the radiation dose of triple-bolus computed
tomography (TBCT) and conventional CT (CCT) urography protocols, analyze the
effects of body mass index (BMI) on radiation dose in each group, and assess
image quality. MATERIALS AND METHODS: We retrospectively reviewed the images of
patients who underwent CCT or TBCT imaging in the management of renal cortical
neoplasms. We used standard volumetric CT dose index (CTDIvol) and dose length
product (DLP) to estimate radiation exposure. In addition, 2 urologists rated the
quality of 20 CT images from each group using a survey with a 5-point Likert
scale. The survey consisted of 10 questions relating to the ability of the scan
to identify relevant renal anatomy. RESULTS: The study included 120 patients.
CTDIvol and DLP were 28.7% and 40.4% lower in the TBCT protocol, respectively
(both P < .001). Increased BMI was associated with a higher DLP for the CCT group
compared with the TBCT group (P < .001). The effect of BMI on CTDIvol did not
differ between the CCT and TBCT groups. There was no difference in the
urologists' assessments of CT image quality. CONCLUSION: In patients with renal
cortical neoplasms, TBCT provides comparable image quality to CCT, with lower
ionizing radiation exposure without compromising image quality. Obese patients
may benefit more from TBCT scans.
PMID- 25123431
TI - Differential synaptic distribution of the scaffold proteins Cask and Caskin1 in
the bovine retina.
AB - Scaffold proteins organize pre- and postsynaptic compartments and align pre- and
postsynaptic events. Cask is a multi-domain scaffold protein essential for brain
synaptic functions. Caskin1 is a recently discovered, brain-specific Cask
interacting multi-domain protein of unknown function. In the present study, we
determined the localization of these scaffold proteins in the bovine retina. The
retina contains tonically active ribbon synapses and conventional synapses. We
found Cask highly enriched in virtually all retinal synapses. Cask was localized
in close vicinity to the active zone protein RIM1/2 in ribbon and conventional
synapses. Caskin1 is also enriched in retinal synapses but is present only in a
subset of Cask-positive synapses. These findings suggest that Cask plays an
important role in all retinal synapses. In contrast, Caskin1 appears to execute
more specialized functions in distinct sets of retinal synapses, possibly for
neuronal pathway formation and stabilization of distinct synaptic contacts.
PMID- 25123432
TI - Landmark-free statistical analysis of the shape of plant leaves.
AB - The shapes of plant leaves are important features to biologists, as they can help
in distinguishing plant species, measuring their health, analyzing their growth
patterns, and understanding relations between various species. Most of the
methods that have been developed in the past focus on comparing the shape of
individual leaves using either descriptors or finite sets of landmarks. However,
descriptor-based representations are not invertible and thus it is often hard to
map descriptor variability into shape variability. On the other hand, landmark
based techniques require automatic detection and registration of the landmarks,
which is very challenging in the case of plant leaves that exhibit high
variability within and across species. In this paper, we propose a statistical
model based on the Squared Root Velocity Function (SRVF) representation and the
Riemannian elastic metric of Srivastava et al. (2011) to model the observed
continuous variability in the shape of plant leaves. We treat plant species as
random variables on a non-linear shape manifold and thus statistical summaries,
such as means and covariances, can be computed. One can then study the principal
modes of variations and characterize the observed shapes using probability
density models, such as Gaussians or Mixture of Gaussians. We demonstrate the
usage of such statistical model for (1) efficient classification of individual
leaves, (2) the exploration of the space of plant leaf shapes, which is important
in the study of population-specific variations, and (3) comparing entire plant
species, which is fundamental to the study of evolutionary relationships in
plants. Our approach does not require descriptors or landmarks but automatically
solves for the optimal registration that aligns a pair of shapes. We evaluate the
performance of the proposed framework on publicly available benchmarks such as
the Flavia, the Swedish, and the ImageCLEF2011 plant leaf datasets.
PMID- 25123430
TI - The hepatitis B virus e antigen suppresses the respiratory burst and mobility of
human monocytes and neutrophils.
AB - The Hepatitis B virus (HBV) e antigen (HBeAg) is a secretory, non-structural
protein, and associated with persistent infection of HBV. Previous studies
indicate that HBeAg is able to regulate T cell-mediated responses, however, the
interaction between HBeAg and the innate immune system is poorly understood. In
this study, we demonstrated that recombinant HBeAg (rHBe) bound to human
peripheral blood monocytes, neutrophils, and B lymphocytes but not to T
lymphocytes. We focused on investigating the effects of HBeAg on monocytes and
neutrophils and found that rHBe decreased the respiratory burst in both types of
cells. Furthermore, we observed that cell migration in monocytes and neutrophils
was suppressed by rHBe in a transwell assay. The attenuation of rHBe was not
caused by a general cytotoxic effect because rHBe treatment stimulated low levels
of cytokine and chemokine production by monocytes and it promoted neutrophil
survival. Since the recruitment of monocytes and neutrophils to the infected site
is crucial for the initiation of inflammation, HBeAg may modulate innate immune
responses by diminishing the respiratory burst and migration of monocytes and
neutrophils, which might interfere with the subsequent innate and adaptive immune
responses against HBV, leading to the establishment of chronic infection.
PMID- 25123433
TI - PECM: prediction of extracellular matrix proteins using the concept of Chou's
pseudo amino acid composition.
AB - The extracellular matrix proteins (ECMs) are widely found in the tissues of
multicellular organisms. They consist of various secreted proteins, mainly
polysaccharides and glycoproteins. The ECMs involve the exchange of materials and
information between resident cells and the external environment. Accurate
identification of ECMs is a significant step in understanding the evolution of
cancer as well as promises wide range of potential applications in therapeutic
targets or diagnostic markers. In this paper, an accurate computational method
named PECM is proposed for identifying ECMs. Here, we explore various sequence
derived discriminative features including evolutionary information, predicted
secondary structure, and physicochemical properties. Rather than simply combining
the features which may bring information redundancy and unwanted noises, we use
Fisher-Markov selector and incremental feature selection approach to search the
optimal feature subsets. Then, we train our model by the technique of support
vector machine (SVM). PECM achieves good prediction performance with the ACC
scores about 86% and 90% on testing and independent datasets, which are
competitive with the state-of-the-art ECMs prediction tools. A web-server named
PECM which implements the proposed approach is freely available at
http://59.73.198.144:8088/PECM/.
PMID- 25123434
TI - Failure analysis of porcupine quills under axial compression reveals their
mechanical response during buckling.
AB - Porcupine quills are natural structures formed by a thin walled conical shell and
an inner foam core. Axial compression tests, differential scanning calorimetry
(DSC), thermogravimetric analysis (TGA) and Fourier transform infrared
spectroscopy (FT-IR) were all used to compare the characteristics and mechanical
properties of porcupine quills with and without core. The failure mechanisms that
occur during buckling were analyzed by scanning electron microscopy (SEM), and it
was found that delamination buckling is mostly responsible for the decrease in
the measured buckling stress of the quills with regard to predicted theoretical
values. Our analysis also confirmed that the foam core works as an energy
dissipater improving the mechanical response of an empty cylindrical shell,
retarding the onset of buckling as well as producing a step wise decrease in
force after buckling, instead of an instantaneous decrease in force typical for
specimens without core. Cell collapse and cell densification in the inner foam
core were identified as the key mechanisms that allow for energy absorption
during buckling.
PMID- 25123435
TI - Fracture mechanics analyses of ceramic/veneer interface under mixed-mode loading.
AB - Few studies have focused on the interface fracture performance of zirconia/veneer
bilayered structure, which plays an important role in dental all-ceramic
restorations. The purpose of this study was to evaluate the fracture mechanics
performance of zirconia/veneer interface in a wide range of mode-mixities (at
phase angles ranging from 0 degrees to 90 degrees ), and to examine the effect
of mechanical properties of the materials and the interface on the fracture
initiation and crack path of an interfacial crack. A modified sandwich test
configuration with an oblique interfacial crack was proposed and calibrated to
choose the appropriate geometry dimensions by means of finite element analysis.
The specimens with different interface inclination angles were tested to failure
under three-point bending configuration. Interface fracture parameters were
obtained with finite element analyses. Based on the interfacial fracture
mechanics, three fracture criteria for crack kinking were used to predict crack
initiation and propagation. In addition, the effects of residual stresses due to
coefficient of thermal expansion mismatch between zirconia and veneer on the
crack behavior were evaluated. The crack initiation and propagation were well
predicted by the three fracture criteria. For specimens at phase angle of 0, the
cracks propagated in the interface; whereas for all the other specimens the
cracks kinked into the veneer. Compressive residual stresses in the veneer can
improve the toughness of the interface structure. The results suggest that, in
zirconia/veneer bilayered structure the veneer is weaker than the interface,
which can be used to explain the clinical phenomenon that veneer chipping rate is
larger than interface delamination rate. Consequently, a veneer material with
larger fracture toughness is needed to decrease the failure rate of all-ceramic
restorations. And the coefficient of thermal expansion mismatch of the substrates
can be larger to produce larger compressive stresses in the veneer.
PMID- 25123436
TI - Assessing microbiological water quality in drinking water distribution systems
with disinfectant residual using flow cytometry.
AB - Flow cytometry (FCM) as a diagnostic tool for enumeration and characterization of
microorganisms is rapidly gaining popularity and is increasingly applied in the
water industry. In this study we applied the method to obtain a better
understanding of total and intact cell concentrations in three different drinking
water distribution systems (one using chlorine and two using chloramines as
secondary disinfectants). Chloramine tended to result in lower proportions of
intact cells than chlorine over a wider residual range, in agreement with
existing knowledge that chloramine suppresses regrowth more efficiently. For
chlorinated systems, free chlorine concentrations above 0.5 mg L(-1) were found
to be associated with relatively low proportions of intact cells, whereas lower
disinfectant levels could result in substantially higher percentages of intact
cells. The threshold for chlorinated systems is in good agreement with guidelines
from the World Health Organization. The fact that the vast majority of samples
failing the regulatory coliform standard also showed elevated proportions of
intact cells suggests that this parameter might be useful for evaluating risk of
failure. Another interesting parameter for judging the microbiological status of
water, the biological regrowth potential, greatly varied among different finished
waters providing potential help for investment decisions. For its measurement, a
simple method was introduced that can easily be performed by water utilities with
FCM capability.
PMID- 25123437
TI - Modelling the metabolic shift of polyphosphate-accumulating organisms.
AB - Enhanced biological phosphorus removal (EBPR) is one of the most important
methods of phosphorus removal in municipal wastewater treatment plants, having
been described by different modelling approaches. In this process, the PAOs
(polyphosphate accumulating organisms) and GAOs (glycogen accumulating organisms)
compete for volatile fatty acids uptake under anaerobic conditions. Recent
studies have revealed that the metabolic pathways used by PAOs in order to obtain
the energy and the reducing power needed for polyhydroxyalkanoates synthesis
could change depending on the amount of polyphosphate stored in the cells. The
model presented in this paper extends beyond previously developed metabolic
models by including the ability of PAO to change their metabolic pathways
according to the content of poly-P available. The processes of the PAO metabolic
model were adapted to new formulations enabling the change from P-driven VFA
uptake to glycogen-driven VFA uptake using the same process equations. The
stoichiometric parameters were changed from a typical PAO coefficient to a
typical GAO coefficient depending on the internal poly-P with Monod-type
expressions. The model was calibrated and validated with seven experiments under
different internal poly-P concentrations, showing the ability to correctly
represent the PAO metabolic shift at low poly-P concentrations. The sensitivity
and error analysis showed that the model is robust and has the ability to
describe satisfactorily the change from one metabolic pathway to the other one,
thereby encompassing a wider range of process conditions found in EBPR plants.
PMID- 25123438
TI - MiR-7b directly targets DC-STAMP causing suppression of NFATc1 and c-Fos
signaling during osteoclast fusion and differentiation.
AB - DC-STAMP is a key regulating molecule of osteoclastogenesis and osteoclast
precursor (OCP) fusion. Emerging lines of evidence showed that microRNAs play
crucial roles in bone metabolism and osteoclast differentiation, but no microRNA
has yet been reported to be directly related to OCPs fusion. Through a
microarray, we found that the expression of miR-7b in RAW264.7 cells was
significantly decreased after induction with M-CSF and RANKL. The overexpression
of miR-7b in RAW264.7 cells attenuated the number of TRAP-positive cells number
and the formation of multinucleated cells, whereas the inhibition of miR-7b
enhanced osteoclastogenesis. Through a dual luciferase reporter assay, we
confirmed that miR-7b directly targets DC-STAMP. Other fusogenic molecules, such
as CD47, ATP6v0d2, and OC-STAMP, were detected to be down-regulated in accordance
with the inhibition of DC-STAMP. Because DC-STAMP also participates in osteoclast
differentiation through the ITAM-ITIM network, multiple osteoclast-specific genes
in the ITAM-ITIM network were detected to identify how DC-STAMP is involved in
this process. The results showed that molecules associated with the ITAM-ITIM
network, such as NFATc1 and OSCAR, which are crucial in osteoclastogenesis, were
consistently altered due to DC-STAMP inhibition. These findings suggest that miR
7b inhibits osteoclastogenesis and cell-cell fusion by directly targeting DC
STAMP. In addition, the inhibition of DC-STAMP and its downstream signals changed
the expression of other fusogenic genes and key regulating genes, such as Nfatc1,
c-fos, Akt, Irf8, Mapk1, and Traf6. In conclusion, our findings indicate that miR
7b may be a potential therapeutic target for the treatment of osteoclast-related
bone disorders.
PMID- 25123439
TI - Docosahexaenoic acid intake ameliorates ketamine-induced impairment of spatial
cognition and learning ability in ICR mice.
AB - Several studies have reported the ketamine-induced cognitive impairment.
Docosahexaenoic acid (DHA) supplementation improves cognitive function in human
infants and protects against learning impairment in patients with Alzheimer's
disease (AD). In this study, we investigated the effect of DHA on ketamine
induced impairment of spatial cognition and learning ability in Institute of
Cancer Research (ICR) mice. Morris water maze (MWM) was used to assess spatial
learning and memory. Gamma-aminobutyric acid (GABA) levels in the hippocampus and
prefrontal cortex were measured using high-performance liquid chromatography
(HPLC). The results showed that intraperitoneal injection of ketamine (30mg/kg,
twice per day) for 4 weeks led to the decline of spatial cognitive ability in
mice, and 420mg/(kgd) DHA supplementation for 6 weeks improved ketamine-induced
spatial cognitive impairment to a certain extent. The up-regulation of GABA
levels in the hippocampus and prefrontal cortex was related to the improvement in
spatial learning. Our results suggested that DHA supplementation would be a
promising intervention to improve ketamine-induced spatial memory and cognitive
dysfunction, and this effect of DHA might be correlated with the up-regulation of
GABA levels.
PMID- 25123440
TI - Sleep deprivation impairs spontaneous object-place but not novel-object
recognition in rats.
AB - Effects of sleep deprivation (SD) on one-trial recognition memory were
investigated in rats using either a spontaneous novel-object or object-place
recognition test. Rats were allowed to explore a field in which two identical
objects were presented. After a delay period, they were placed again in the same
field in which either: (1) one of the two objects was replaced by another object
(novel-object recognition); or (2) one of the sample objects was moved to a
different place (object-place recognition), and their exploration behavior to
these objects was analyzed. Four hours SD immediately after the sample phase
(early SD group) disrupted object-place recognition but not novel-object
recognition, while SD 4-8h after the sample phase (delayed SD group) did not
affect either paradigm. The results suggest that sleep selectively promotes the
consolidation of hippocampal dependent memory, and that this effect is limited to
within 4h after learning.
PMID- 25123441
TI - The glossopharyngeal nerve controls epithelial expression of Sprr2a and Krt13
around taste buds in the circumvallate papilla.
AB - Tastants reach the tip of taste bud cells through taste pores which are openings
in the epithelium. We found Sprr2a is selectively expressed in the upper layer of
the epithelium surrounding taste buds in the circumvallate papilla (CV) where the
epithelium is organized into taste pores. Sprr2a is a member of a small proline
rich protein family, which is suggested to be involved in the
restitution/migration phase of epithelial wound healing. The expression of Sprr2a
was restricted to the upper layer and largely segregated with Ptch1 expression
that is restricted to the basal side of the epithelium around the taste buds.
Denervation resulted in the gradual loss of Sprr2a-expressing cells over 10 days
similarly to that of taste bud cells which is in contrast to the rapid loss of
Ptch1 expression. We also found that denervation caused an increase of Keratin
(Krt)13 expression around taste buds that corresponded with the disappearance of
Sprr2a and Ptch1 expression. Taste buds were surrounded by Krt13-negative cells
in the CV in control mice. However, at 6 days post-denervation, taste buds were
tightly surrounded by Krt13-positive cells. During taste bud development, taste
bud cells emerged together with Krt13-negtive cells, and Sprr2a expression was
increased along with the progress of taste bud development. These results
demonstrate that regional gene expression surrounding taste buds is associated
with taste bud formation and controlled by the innervating taste nerve.
PMID- 25123442
TI - Motor and cognitive impairment in a mouse model of ischemic carotid artery
disease.
AB - We have recently established a novel mouse model of bilateral common carotid
artery gradual occlusion. This model serves as a mimic of severe carotid artery
disease with multiple cerebral infarctions induced by cerebrovascular
insufficiency. In this study, we examined whether locomotor and cognitive
impairment was induced in these mice using a test battery for neurological and
cognitive functions. Adult C57BL/6J male mice were subjected to either ameroid
constrictor (AC) placement to gradually narrow the bilateral common carotid
arteries or to sham surgery. At 28 days post-surgery, locomotor activity was
assessed by rotarod and wire hang tests, and cognitive function was assessed
using the Y-maze and Morris water maze tests. Rotarod and wire hang tests showed
a significantly shorter latency to fall in mice subjected to the placement of ACs
compared with sham surgery mice. AC-implanted mice showed significant impairments
in working memory on the Y-maze test and in spatial learning and reference memory
on the Morris water maze test. Therefore, the current mouse model with AC
placement on the bilateral common carotid arteries showed locomotor disability,
learning deficits, and memory impairment, which well-replicated the outcomes of
patients with ischemic carotid artery disease. This model will be useful for
investigating the mechanisms underlying the neurological and cognitive deficits
following cerebrovascular insufficiency and for exploring pharmacological
interventions for stroke patients with severe carotid artery disease.
PMID- 25123443
TI - KB-R7943, an inhibitor of the reverse Na(+)/Ca(2+) exchanger, does not modify
secondary pathology in the thalamus following focal cerebral stroke in rats.
AB - Remote areas connected to cortical infarcts, such as the thalamus, are affected
by stroke due to delayed retrograde degeneration of afferent connections. This is
temporally associated with the accumulation of beta-amyloid (Abeta) and calcium.
Here we tested a hypothesis that prevention of excessive Ca(2+) influx into the
axoplasm via the reverse Na(+)/Ca(2+) exchanger (NCX) would provide axonal
protection and eventually lessen the Abeta and calcium load in the thalamus. We
found that chronic treatment with a specific inhibitor of the reverse NCX, KB
R7943 (30mg/kg once daily, 27 days) after middle cerebral artery occlusion did
not prevent atypical secondary pathology in the thalamus or improve functional
outcome. The present data do not support a role for reverse NCX activity in the
complex pathology within the thalamus after cerebral ischemia.
PMID- 25123444
TI - Evaluation of several micro RNA (miRNA) levels in children and adolescents with
attention deficit hyperactivity disorder.
AB - Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent
childhood disorders, although disorders etiology and pathogenesis remains
unknown, several theories about ADHD development have been proposed and many
researchers believe that it is caused by both genetic and environmental factors.
In this study we evaluated miR18a-5p, miR22-3p, miR24-3p, miR106b-5p, miR107,
miR125b-5p and miR155a-5p levels in child and adolescent ADHD patients. The
research sample consisted a group of 52 ADHD patients, and 52 healthy volunteer
controls. There was no significant difference in age and sex between the two
groups (p>0.05). miRNA 18a-5p, 22-3p, 24-3p, 106b-5p and 107 levels were
statistically significantly decreased in ADHD patients(p<0.05). miRNA 155a-5p
levels were increased in patients group (p<0.05). The positive predictive value
(PPV) and negative predictive value of miR107 was estimated for the cutoff point
of 0.4480. PPV was 70% and NPV was 86.5% for the taken cut off point. There could
be a close relationship between levels of circulating miRNAs and ADHD. If we
could understand how the signaling pathways arranged by miRNAs, impact on CNS
development, function and pathology this can improve our knowledge about ADHD
etiology and treatment.
PMID- 25123445
TI - The free-exploratory paradigm as a model of trait anxiety in female rats: test
retest reliability.
AB - The free-exploratory paradigm has been proposed as a model of trait anxiety and
as such has been proven stable over time, which is a sine qua non condition for
any model proposing to evaluate a personality trait. However this stability has
only been shown for male rats. Considering that anxiety disorders are most
prevalent in women, it's crucial that females are tested in animal models. With
this in mind, the stability over time of female rats in the free-exploratory
paradigm was evaluated using a test-retest procedure. The behaviour of drug
naive, adult, female, Wistar rats was measured in the free-exploratory apparatus
on two occasions two months apart. The following parameters were evaluated:
percentage of distance travelled in the novel compartment; number of attempts to
enter the novel compartment; percentage of time spent in the novel compartment;
and percentage of time rearing in the novel compartment. Subsequently, the
intraclass correlation coefficient (ICC) and the kappa index (kappa) were
calculated for each of these parameters. The "percentage of time spent in the
novel compartment" (ICC=0.727; kappa=0.457), the "percentage of distance
travelled in the novel compartment" (ICC=0.680; kappa=0.370), and the "percentage
of time rearing in the novel compartment" (ICC=0.648; kappa=0.309) were found to
be stable over time. Analysis of these parameters indicated fair to substantial
reliability over time in two-month inter-trial interval. Therefore, our results
support the idea of the free-exploratory paradigm as an animal model of trait
anxiety for female rats.
PMID- 25123446
TI - The re-organization of functional brain networks in pharmaco-resistant epileptic
patients who respond to VNS.
AB - Vagal nerve stimulation (VNS) is a therapeutic add-on treatment for patients with
pharmaco-resistant epilepsy. The mechanism of action is still largely unknown.
Previous studies have shown that brain network topology during the inter-ictal
period in epileptic patients deviates from normal configuration. In the present
paper, we investigate the relationship between clinical improvement induced by
VNS and alterations in brain network topology. We hypothesize that, as a
consequence of the VNS add-on treatment, functional brain network architecture
shifts back toward a more efficient configuration in patients responding to VNS.
Electroencephalographic (EEG) recordings from ten patients affected by pharmaco
resistant epilepsy were analyzed in the classical EEG frequency bands. The phase
lag index (PLI) was used to estimate functional connectivity between EEG channels
and the minimum spanning tree (MST) was computed in order to characterize VNS
induced alterations in network topology in a bias-free way. Our results revealed
a clear network re-organization, in terms of MST modification, toward a more
integrated architecture in patients responding to the VNS. In particular, the
results show a significant interaction effect between benefit from VNS
(responders/non-responders) and condition (pre/post VNS implantation) in the
theta band. This finding suggests that the positive effect induced by VNS add-on
treatment in epileptic patients is related to a clear network re-organization and
that this network modification can reveal the long debated mechanism of action of
VNS. Therefore, MST analysis could be useful in evaluating and monitoring the
efficacy of VNS add-on treatment potentially in both epilepsy and psychiatric
diseases.
PMID- 25123447
TI - Different effects of cabergoline and bromocriptine on metabolic and
cardiovascular risk factors in patients with elevated prolactin levels.
AB - Hyperprolactinaemia is suggested to be associated with metabolic and hormonal
complications. No previous study has compared the effect of different dopamine
agonists on plasma lipids, carbohydrate metabolism markers and cardiovascular
risk factors in patients with elevated prolactin levels. The study included eight
bromocriptine-resistant women with prolactinoma (group 1) and twelve matched
women with hyperprolactinaemia unrelated to prolactinoma (group 2). Group 1 was
then treated with cabergoline, while group 2 with bromocriptine. Plasma lipids,
glucose homeostasis markers and plasma levels of prolactin, insulin-like growth
factor-1 (IGF-1) and cardiovascular risk factors were assessed before and after 6
months of therapy. Both treatments normalized plasma prolactin levels.
Cabergoline reduced triglycerides, 2-hr post-challenge plasma glucose, the
homeostatic model assessment of insulin resistance (HOMA-IR), and circulating
levels of IGF-1, free fatty acids (FFA), uric acid, high-sensitivity C-reactive
protein (hsCRP), homocysteine and fibrinogen, as well as increased HDL
cholesterol and 25-hydroxyvitamin D. With the exception of a reduction in HOMA
IR, bromocriptine treatment produced no significant effect on the investigated
biomarkers. Cabergoline was superior to bromocriptine in affecting 2-hr post
challenge plasma glucose levels, HOMA-IR, as well as circulating levels of IGF-1,
FFA, uric acid, hsCRP, homocysteine, fibrinogen and 25-hydroxyvitamin D. Our
results may suggest that cabergoline is superior to bromocriptine when it comes
to affecting atherogenic dyslipidaemia, insulin sensitivity and circulating
levels of cardiovascular risk factors in hyperprolactinaemic patients. These
findings seem to support previous observations that cabergoline may be a better
treatment for patients with elevated prolactin levels than bromocriptine.
PMID- 25123448
TI - Prevalence of childbirth fear in an Australian sample of pregnant women.
AB - BACKGROUND: Childbirth fear is reported to affect around 20% of women. However
reporting on levels of symptom severity vary. Unlike Scandinavian countries,
there has been limited focus on childbirth fear in Australia. The aim of this
paper is to determine the prevalence of low, moderate, high and severe levels of
childbirth fear in a large representative sample of pregnant women drawn from a
large randomised controlled trial and identify demographic and obstetric
characteristics associated with childbirth fear. METHOD: Using a descriptive
cross-sectional design, 1,410 women in their second trimester were recruited from
one of three public hospitals in south-east Queensland. Participants were
screened for childbirth fear using the Wijma Delivery Expectancy/Experience
Questionnaire Version A (WDEQ-A). Associations of demographic and obstetric
factors and levels of childbirth fear between nulliparous and multiparous women
were investigated. RESULTS: Prevalence of childbirth fear was 24% overall, with
31.5% of nulliparous women reporting high levels of fear (score >= 66 on the WDEQ
A) compared to 18% of multiparous women. Childbirth fear was associated with paid
employment, parity, and mode of last birth, with higher levels of fear in first
time mothers (p < 0.001) and in women who had previously had an operative birth
(p < 0.001). CONCLUSION: Prevalence of childbirth fear in Australian women was
comparable to international rates. Significant factors associated with childbirth
fear were being in paid employment, and obstetric characteristics such as parity
and birth mode in the previous pregnancy. First time mothers had higher levels of
fear than women who had birthed before. A previous operative birth was fear
provoking. Experiencing a previous normal birth was protective of childbirth
fear.
PMID- 25123449
TI - Bright-white beetle scales optimise multiple scattering of light.
AB - Whiteness arises from diffuse and broadband reflection of light typically
achieved through optical scattering in randomly structured media. In contrast to
structural colour due to coherent scattering, white appearance generally requires
a relatively thick system comprising randomly positioned high refractive-index
scattering centres. Here, we show that the exceptionally bright white appearance
of Cyphochilus and Lepidiota stigma beetles arises from a remarkably optimised
anisotropy of intra-scale chitin networks, which act as a dense scattering media.
Using time-resolved measurements, we show that light propagating in the scales of
the beetles undergoes pronounced multiple scattering that is associated with the
lowest transport mean free path reported to date for low-refractive-index
systems. Our light transport investigation unveil high level of optimisation that
achieves high-brightness white in a thin low-mass-per-unit-area anisotropic
disordered nanostructure.
PMID- 25123452
TI - Could the Affordable Care Act Medicaid expansion affect otolaryngology-head and
neck surgery?
PMID- 25123450
TI - Comparison of primary target volumes delineated on four-dimensional CT and 18 F
FDG PET/CT of non-small-cell lung cancer.
AB - BACKGROUND: To determine the optimal threshold of 18 F-fluorodexyglucose (18 F
FDG) positron emission tomography CT (PET/CT) images that generates the best
volumetric match to internal gross target volume (IGTV) based on four-dimensional
CT (4DCT) images. METHODS: Twenty patients with non-small cell lung cancer
(NSCLC) underwent enhanced three-dimensional CT (3DCT) scan followed by enhanced
4DCT scan of the thorax under normal free breathing with the administration of
intravenous contrast agents. A total of 100 ml of ioversol was injected
intravenously, 2 ml/s for 3DCT and 1 ml/s for 4DCT. Then 18 F-FDG PET/CT scan was
performed based on the same positioning parameters (the same immobilization
devices and identical position verified by laser localizer as well as skin
marks). Gross target volumes (GTVs) of the primary tumor were contoured on the
ten phases images of 4DCT to generate IGTV10. GTVPET were determined with eight
different threshold using an auto-contouring function. The differences in the
position, volume, concordance index (CI) and degree of inclusion (DI) of the
targets between GTVPET and IGTV10 were compared. RESULTS: The images from
seventeen patients were suitable for further analysis. Significant differences
between the centric coordinate positions of GTVPET (excluding GTVPET15%) and
IGTV10 were observed only in z axes (P < 0.05). GTVPET15%, GTVPET25% and
GTVPET2.0 were not statistically different from IGTV10 (P < 0.05). GTVPET15%
approximated closely to IGTV10 with median percentage volume changes of 4.86%.
The best CI was between IGTV10 and GTVPET15% (0.57). The best DI of IGTV10 in
GTVPET was IGTV10 in GTVPET15% (0.80). CONCLUSION: None of the PET-based contours
had both close spatial and volumetric approximation to the 4DCT IGTV10. At
present 3D-PET/CT should not be used for IGTV generation.
PMID- 25123451
TI - Adjuvant-dependent regulation of interleukin-17 expressing gammadelta T cells and
inhibition of Th2 responses in allergic airways disease.
AB - BACKGROUND: Th2 immune responses are linked primarily to mild and moderate
asthma, while Th17 cells, Interleukin-17A (IL-17) and neutrophilia have been
implicated in more severe forms of disease. How Th2-dependent allergic reactions
are influenced by Th17 and IL-17-gammadelta T cells is poorly understood. In
murine models, under some conditions, IL-17 promotes Th2-biased airway
inflammatory responses. However, IL-17-gammadelta T cells have been implicated in
the inhibition and resolution of allergic airway inflammation and
hyperresponsiveness (AHR). METHODS: We compared airway responses in Balb/c mice
sensitized to OVA with (and without) a Th2-skewing aluminum-based adjuvant and
the IL-17 skewing, complete Freund's adjuvant (CFA). AHR was measured invasively
by flexiVent, while serum OVA-IgE was quantified by an enzyme immunoassay. Airway
inflammatory and cytokine profiles, and cellular sources of IL-17 were assessed
from bronchoalveolar lavage and/or lungs. The role of gammadelta T cells in these
responses was addressed in OVA/CFA sensitized mice using a gammadelta T cell
antibody. RESULTS: Following OVA challenge, all mice exhibited mixed
eosinophilic/neutrophilic airway inflammatory profiles and elevated serum OVA
IgE. Whereas OVA/alum sensitized mice had moderate inflammation and AHR, OVA/CFA
sensitized mice had significantly greater inflammation but lacked AHR. This
correlated with a shift in IL-17 production from CD4+ to gammadelta T cells.
Additionally, OVA/CFA sensitized mice, given a gammadelta TCR stimulatory
antibody, showed increased frequencies of IL-17-gammadelta T cells and diminished
airway reactivity and eosinophilia. CONCLUSIONS: Thus, the conditions of antigen
sensitization influence the profile of cells that produce IL-17, the balance of
which may then modulate the airway inflammatory responses, including AHR. The
possibility for IL-17-gammadelta T cells to reduce AHR and robust eosinophilic
inflammation provides evidence that therapeutic approaches focused on stimulating
and increasing airway IL-17-gammadelta T cells may be an effective alternative in
treating steroid resistant, severe asthma.
PMID- 25123453
TI - High expression of microRNA-130b correlates with poor prognosis of patients with
hepatocellular carcinoma.
AB - BACKGROUND: Whether microRNA-130b(miR-130b) can serve as a prognostic biomarker
of hepatocellular carcinoma (HCC) has not been investigated. In the present
study, we investigated the feasibility of miR-130b as a novel prognostic
biomarker for HCC. METHODS: We retrospectively investigated 97 patients diagnosed
with HCC who underwent routine curative surgery between May 2007 and July 2012.
miR-130b expression in HCC tissues and paired normal adjacent liver tissues was
measured by reverse transcription and real-time PCR (RT-PCR). Survival curves
were plotted using the Kaplan-Meier method and differences in survival rates were
analyzed using the log-rank test. RESULTS: miR-130b expression level was
significantly higher in HCC tissues compared with normal adjacent liver tissues
(P<0.0001). The 5-year overall survival (OS) of high miR-130b expression group
was significantly shorter than that of low miR-130b expression group (43.6% vs.
71.5%; P=0.022). Moreover, the 5-year disease-free survival (DFS) of high miR
130b expression group was also significantly shorter than that of low miR-130b
expression group (25.9% vs. 63.9%; P=0.012). In a multivariate Cox model, we
found that miR-130b expression was an independent prognostic factor for both 5
year OS (hazards ratio [HR] =2.523, 95% confidence interval [CI] =1.024-7.901,
P=0.011) and 5-year DFS (HR=4.003, CI=1.578-7.899, P=0.005) in HCC. CONCLUSION:
The results indicated that high expression of microRNA-130b was correlated with
significant characteristics of patients with HCC, and it might be useful as a
novel prognostic biomarker for HCC. VIRTUAL SLIDES: The virtual slide(s) for this
article can be found here:
http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_160.
PMID- 25123454
TI - Evidence for functional convergence in genes upregulated by herbivores ingesting
plant secondary compounds.
AB - BACKGROUND: Nearly 40 years ago, Freeland and Janzen predicted that liver
biotransformation enzymes dictated diet selection by herbivores. Despite decades
of research on model species and humans, little is known about the
biotransformation mechanisms used by mammalian herbivores to metabolize plant
secondary compounds (PSCs). We investigated the independent evolution of PSC
biotransformation mechanisms by capitalizing on a dramatic diet change event-the
dietary inclusion of creosote bush (Larrea tridentata)-that occurred in the
recent evolutionary history of two species of woodrats (Neotoma lepida and N.
bryanti). RESULTS: By comparing gene expression profiles of two populations of
woodrats with evolutionary experience to creosote and one population naive to
creosote, we identified genes either induced by a diet containing creosote PSCs
or constitutively higher in populations with evolutionary experience of creosote.
Although only one detoxification gene (an aldo-keto reductase) was induced by
both experienced populations, these populations converged upon functionally
equivalent strategies to biotransform the PSCs of creosote bush by constitutively
expressing aldehyde and alcohol dehydrogenases, Cytochromes P450s,
methyltransferases, glutathione S-transferases and sulfotransferases. The
response of the naive woodrat population to creosote bush was indicative of
extreme physiological stress. CONCLUSIONS: The hepatic detoxification system of
mammals is notoriously complex, with hundreds of known biotransformation enzymes.
The comparison herein of woodrat taxa that differ in evolutionary and ecological
experience with toxins in creosote bush reveals convergence in the overall
strategies used by independent species after a historical shift in diet. In
addition, remarkably few genes seemed to be important in this dietary shift. The
research lays the requisite groundwork for future studies of specific
biotransformation pathways used by woodrats to metabolize the toxins in creosote
and the evolution of diet switching in woodrats. On a larger level, this work
advances our understanding of the mechanisms used by mammalian herbivores to
process toxic diets and illustrates the importance of the selective relationship
of PSCs in shaping herbivore diversity.
PMID- 25123455
TI - A secure and efficient chaotic map-based authenticated key agreement scheme for
telecare medicine information systems.
AB - Advancement in network technology provides new ways to utilize telecare medicine
information systems (TMIS) for patient care. Although TMIS usually faces various
attacks as the services are provided over the public network. Recently, Jiang et
al. proposed a chaotic map-based remote user authentication scheme for TMIS.
Their scheme has the merits of low cost and session key agreement using Chaos
theory. It enhances the security of the system by resisting various attacks. In
this paper, we analyze the security of Jiang et al.'s scheme and demonstrate that
their scheme is vulnerable to denial of service attack. Moreover, we demonstrate
flaws in password change phase of their scheme. Further, our aim is to propose a
new chaos map-based anonymous user authentication scheme for TMIS to overcome the
weaknesses of Jiang et al.'s scheme, while also retaining the original merits of
their scheme. We also show that our scheme is secure against various known
attacks including the attacks found in Jiang et al.'s scheme. The proposed scheme
is comparable in terms of the communication and computational overheads with
Jiang et al.'s scheme and other related existing schemes. Moreover, we
demonstrate the validity of the proposed scheme through the BAN (Burrows, Abadi,
and Needham) logic.
PMID- 25123456
TI - QoS-aware health monitoring system using cloud-based WBANs.
AB - Wireless Body Area Networks (WBANs) are amongst the best options for remote
health monitoring. However, as standalone systems WBANs have many limitations due
to the large amount of processed data, mobility of monitored users, and the
network coverage area. Integrating WBANs with cloud computing provides effective
solutions to these problems and promotes the performance of WBANs based systems.
Accordingly, in this paper we propose a cloud-based real-time remote health
monitoring system for tracking the health status of non-hospitalized patients
while practicing their daily activities. Compared with existing cloud-based WBAN
frameworks, we divide the cloud into local one, that includes the monitored users
and local medical staff, and a global one that includes the outer world. The
performance of the proposed framework is optimized by reducing congestion,
interference, and data delivery delay while supporting users' mobility. Several
novel techniques and algorithms are proposed to accomplish our objective. First,
the concept of data classification and aggregation is utilized to avoid clogging
the network with unnecessary data traffic. Second, a dynamic channel assignment
policy is developed to distribute the WBANs associated with the users on the
available frequency channels to manage interference. Third, a delay-aware routing
metric is proposed to be used by the local cloud in its multi-hop communication
to speed up the reporting process of the health-related data. Fourth, the delay
aware metric is further utilized by the association protocols used by the WBANs
to connect with the local cloud. Finally, the system with all the proposed
techniques and algorithms is evaluated using extensive ns-2 simulations. The
simulation results show superior performance of the proposed architecture in
optimizing the end-to-end delay, handling the increased interference levels,
maximizing the network capacity, and tracking user's mobility.
PMID- 25123457
TI - Using data envelopment analysis to analyse the efficiency of primary care units.
AB - In this paper we analyse the efficiency of primary care centres (PCCs) adopting
Information and Communication Technology (ICT) devices, using a new database on
primary care centres in the Basque Region in Spain. Using a four-stage Data
Envelopment Analysis methodology, we are able to explicitly take into account the
role of ICT in affecting the efficiency of primary care centres. We understand
that this is the first time that ICT enters into the determination of efficiency
of the health sector. The role of exogenous factors is explicitly considered in
this analysis and shows that including these variables is not neutral to the
efficiency evaluation, but leads to an efficiency indicator that only encompasses
the effect of managerial skills. The paper provides some useful policy
implications regarding the role of ICT in improving the efficiency of primary
care units.
PMID- 25123459
TI - [Skin adnexal tumors with follicular differentiation].
AB - Skin adnexal tumors with predominantly follicular differentiation represent a
clinicopathological heterogeneous group of neoplasms and are classified according
to the cytologically achieved differentiation of the follicular compartment.
Given the complex structure of non-neoplastic hair follicles it is not surprising
to find varying differentiations in neoplasms and there are overlapping
clinicopathological features between the established entities. The use of
immunohistochemical staining has only a limited value in the diagnosis of
follicular neoplasms.
PMID- 25123460
TI - Methodological aspects of in vitro assessment of bio-accessible risk element pool
in urban particulate matter.
AB - In vitro tests simulating the elements release from inhaled urban particulate
matter (PM) with artificial lung fluids (Gamble's and Hatch's solutions) and
simulated gastric and pancreatic solutions were applied for an estimation of
hazardous element (As, Cd, Cr, Hg, Mn, Ni, Pb and Zn) bio-accessibility in this
material. An inductively coupled plasma optical emission spectrometry (ICP-OES)
and an inductively coupled plasma mass spectrometry (ICP-MS) were employed for
the element determination in extracted solutions. The effect of the extraction
agent used, extraction time, sample-to-extractant ratio, sample particle size
and/or individual element properties was evaluated. Different patterns of
individual elements were observed, comparing Hatch's solution vs. simulated
gastric and pancreatic solutions. For Hatch's solution, a decreasing sample-to
extractant ratio in a PM size fraction of <0.063 mm resulted in increasing
leached contents of all investigated elements. As already proved for other
operationally defined extraction procedures, the extractable element portions are
affected not only by their mobility in the particulate matter itself but also by
the sample preparation procedure. Results of simulated in vitro tests can be
applied for the reasonable estimation of bio-accessible element portions in the
particulate matter as an alternative method, which, consequently, initiates
further examinations including potential in vivo assessments.
PMID- 25123458
TI - PPM1D silencing by RNA interference inhibits the proliferation of lung cancer
cells.
AB - BACKGROUND: PPM1D (protein phosphatase, Mg2+/Mn2+ dependent, 1D) has been
reported to be involved in multiple human tumors. This study was designed to
investigate the functional role of PPM1D in lung cancer cells. METHODS:
Expression levels of PPM1D were analyzed in A549 and H1299 cells by real-time PCR
and Western blotting. Lentivirus-mediated short hairpin RNA (shRNA) was used to
knock down PPM1D expression in both cell lines. The effects of PPM1D on lung
cancer cell growth were investigated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide), colony formation and flow cytometry assays.
RESULTS: Knockdown of PPM1D in lung cancer cells resulted in decreased cell
proliferation and impaired colony formation ability. Moreover, flow cytometry
analysis showed that knockdown of PPM1D arrested cell cycle at the G0/G1 phase.
Furthermore, PPM1D silencing downregulated the expression of cyclin B1 in H1299
cells. Therefore, it is reasonable to speculate that the mechanisms by which
PPM1D knockdown alleviates cell growth may be partly via the induction of cell
cycle arrest due to the suppression of cyclin B1. CONCLUSIONS: These results
suggest that PPM1D silencing by RNA interference (RNAi) may be a potential
therapeutic approach for the treatment of lung cancer.
PMID- 25123461
TI - Oxidative stress and Ca(2+) signals involved on cadmium-induced apoptosis in rat
hepatocyte.
AB - Cadmium (Cd) is an important industrial and environmental pollutant. In animals,
the liver is the major target organ of Cd toxicity. In this study, rat
hepatocytes were treated with 2.5~10 MUM Cd for various durations. Studies on
nuclear morphology, chromatin condensation, and apoptotic cells demonstrate that
Cd concentrations ranging within 2.5~10 MUM induced apoptosis. The early-stage
marker of apoptosis, i.e., decreased mitochondrial membrane potential, was
observed as early as 1.5 h at 5 MUM Cd. Significant (P < 0.01) reactive oxygen
species (ROS) production at 5 MUM Cd and 0.75 h occurred prior to the decrease of
the mitochondrial membrane potential, suggesting the involvement of ROS in
mitochondrial membrane damage. Glutathione (GSH) level significantly decreased
after cell treatment with 5 and 10 MUM Cd after 12 h (P < 0.01). Meanwhile, the
intracellular free Ca(2+) concentration ([Ca(2+)] i ) of Cd-exposed cells
significantly increased (P < 0.01) at 1.5 h, and pretreatment with the calcium
chelator Bapta-AM partially blocked Cd-induced apoptosis. This finding indicated
that the elevation of [Ca(2+)] i may play an important role in apoptosis.
Overall, these results showed that oxidative stress and Ca(2+) signaling were
critical mediators of the Cd-induced apoptosis of rat hepatocytes.
PMID- 25123462
TI - Possible correlation of selenoprotein W with inflammation factors in chicken
skeletal muscles.
AB - The aim of the present study was to investigate the possible correlation of
selenoprotein W (SelW) with inflammatory injury induced by dietary selenium (Se)
deficiency in chicken. One-day-old male chickens were fed either a commercial
diet or a Se-deficient diet for 55 days. Then, the expression levels of SelW
messenger RNA (mRNA) and inflammation-related genes (NF-kappaB, TNF-alpha, iNOS,
COX-2, and PTGES) in chicken skeletal muscles (wing muscle, pectoral muscle, and
thigh muscle) were determined at 15, 25, 35, 45, and 55 days old, respectively.
In addition, the correlation between SelW mRNA expression and inflammation
related genes were assessed. The results showed that dietary Se deficiency
reduced the mRNA expression of SelW in chicken wing, pectorals, and thigh
muscles. In contrast, Se deficiency increased the mRNA expression levels of
inflammation-related genes in chicken skeletal muscle tissues at different time
points. The Pearson's correlation coefficients showed that the mRNA expression
levels of inflammation-related genes were significantly negative related to SelW
(p < 0.05). These data showed that Se deficiency induced the inflammatory
response in chicken skeletal muscle. As one important selenoprotein gene in
skeletal muscles, SelW may play a role in the regulation of inflammation reaction
in Se-deficiency myopathy.
PMID- 25123463
TI - Zinc-binding sites on selected flavonoids.
AB - Flavonoids have attracted increased attention due to their broad bioactivities
related to health and diseases. Modulating metal homeostasis may play an
important role in their bioactivities. Recent studies have suggested that dietary
flavonoids may affect zinc homeostasis, uptake, and transport. In this work, the
zinc-binding sites on a few selected flavonoids have been investigated by (1)H
NMR spectroscopy under physiological relevant pH and the species formed were
verified by mass spectrometry. Zinc binding induces distinct changes in the
proton resonances on the flavonoid rings, providing useful information to locate
the Zn-binding sites. No Zn-binding was observed with flavone which lacks a
chelation site. Zinc was found to bind to the 3-hydroxyl-4-keto, catechol, and 5
hydroxyl-4-keto chelation sites of flavonol, 3',4'-dihydroxylflavone and chrysin,
respectively. Kaempferol and myricetin chelate zinc at the 3-hydroxyl-4-keto site
while rutin binds zinc preferentially at the 5-hydroxyl-4-keto site. However,
morin appears to bind zinc at the 1-ether-2-hydroxyl site.
PMID- 25123464
TI - Security analysis and improvements of authentication and access control in the
Internet of Things.
AB - Internet of Things is a ubiquitous concept where physical objects are connected
over the internet and are provided with unique identifiers to enable their self
identification to other devices and the ability to continuously generate data and
transmit it over a network. Hence, the security of the network, data and sensor
devices is a paramount concern in the IoT network as it grows very fast in terms
of exchanged data and interconnected sensor nodes. This paper analyses the
authentication and access control method using in the Internet of Things
presented by Jing et al. (Authentication and Access Control in the Internet of
Things. In Proceedings of the 2012 32nd International Conference on Distributed
Computing Systems Workshops, Macau, China, 18-21 June 2012, pp. 588-592).
According to our analysis, Jing et al.'s protocol is costly in the message
exchange and the security assessment is not strong enough for such a protocol.
Therefore, we propose improvements to the protocol to fill the discovered
weakness gaps. The protocol enhancements facilitate many services to the users
such as user anonymity, mutual authentication, and secure session key
establishment. Finally, the performance and security analysis show that the
improved protocol possesses many advantages against popular attacks, and achieves
better efficiency at low communication cost.
PMID- 25123466
TI - Design and implementation of a RF powering circuit for RFID tags or other
batteryless embedded devices.
AB - A RF powering circuit used in radio-frequency identification (RFID) tags and
other batteryless embedded devices is presented in this paper. The RF powering
circuit harvests energy from electromagnetic waves and converts the RF energy to
a stable voltage source. Analysis of a NMOS gate-cross connected bridge rectifier
is conducted to demonstrate relationship between device sizes and power
conversion efficiency (PCE) of the rectifier. A rectifier with 38.54% PCE under
normal working conditions is designed. Moreover, a stable voltage regulator with
a temperature and voltage optimizing strategy including adoption of a combination
resistor is developed, which is able to accommodate a large input range of 4 V to
12 V and be immune to temperature variations. Latch-up prevention and noise
isolation methods in layout design are also presented. Designed with the HJTC
0.25 MUm process, this regulator achieves 0.04 mV/ degrees C temperature
rejection ratio (TRR) and 2.5 mV/V voltage rejection ratio (VRR). The RF powering
circuit is also fabricated in the HJTC 0.25 MUm process. The area of the RF
powering circuit is 0.23 * 0.24 mm2. The RF powering circuit is successfully
integrated with ISO/IEC 15693-compatible and ISO/IEC 14443-compatible RFID tag
chips.
PMID- 25123465
TI - Acoustic devices for particle and cell manipulation and sensing.
AB - An emerging demand for the precise manipulation of cells and particles for
applications in cell biology and analytical chemistry has driven rapid
development of ultrasonic manipulation technology. Compared to the other
manipulation technologies, such as magnetic tweezing, dielectrophoresis and
optical tweezing, ultrasonic manipulation has shown potential in a variety of
applications, with its advantages of versatile, inexpensive and easy integration
into microfluidic systems, maintenance of cell viability, and generation of
sufficient forces to handle particles, cells and their agglomerates. This article
briefly reviews current practice and reports our development of various
ultrasonic standing wave manipulation devices, including simple devices
integrated with high frequency (>20 MHz) ultrasonic transducers for the
investigation of biological cells and complex ultrasonic transducer array systems
to explore the feasibility of electronically controlled 2-D and 3-D manipulation.
Piezoelectric and passive materials, fabrication techniques, characterization
methods and possible applications are discussed. The behavior and performance of
the devices have been investigated and predicted with computer simulations, and
verified experimentally. Issues met during development are highlighted and
discussed. To assist long term practical adoption, approaches to low-cost, wafer
level batch-production and commercialization potential are also addressed.
PMID- 25123467
TI - Implantable impedance plethysmography.
AB - We demonstrate by theory, as well as by ex vivo and in vivo measurements that
impedance plethysmography, applied extravascularly directly on large arteries, is
a viable method for monitoring various cardiovascular parameters, such as blood
pressure, with high accuracy. The sensor is designed as an implant to monitor
cardiac events and arteriosclerotic progression over the long term.
PMID- 25123468
TI - Liquid seal for temperature sensing with fiber-optic refractometers.
AB - Liquid sealing is an effective method to convert a fiber-optic refractometer into
a simple and highly sensitive temperature sensor. A refractometer based on the
thin-core fiber modal interferometer is sealed in a capillary tube filled with
Cargille oil. Due to the thermo-optic effect of the sealing liquid, the high
refractive-index sensitivity refractometer is subsequently sensitive to the
ambient temperature. It is found that the liquid-sealed sensor produces a highest
sensitivity of -2.30 nm/ degrees C, which is over 250 times higher than its
intrinsic sensitivity before sealing and significantly higher than that of a
grating-based fiber sensors. The sensing mechanisms, including the incidental
temperature-induced strain effect, are analyzed in detail both theoretically and
experimentally. The liquid sealing technique is easy and low cost, and makes the
sensor robust and insensitive to the surrounding refractive index. It can be
applied to other fiber-optic refractometers for temperature sensing.
PMID- 25123469
TI - Time- and computation-efficient calibration of MEMS 3D accelerometers and
gyroscopes.
AB - We propose calibration methods for microelectromechanical system (MEMS) 3D
accelerometers and gyroscopes that are efficient in terms of time and
computational complexity. The calibration process for both sensors is simple,
does not require additional expensive equipment, and can be performed in the
field before or between motion measurements. The methods rely on a small number
of defined calibration measurements that are used to obtain the values of 12
calibration parameters. This process enables the static compensation of sensor
inaccuracies. The values detected by the 3D sensor are interpreted using a
generalized 3D sensor model. The model assumes that the values detected by the
sensor are equal to the projections of the measured value on the sensor
sensitivity axes. Although this finding is trivial for 3D accelerometers, its
validity for 3D gyroscopes is not immediately apparent; thus, this paper
elaborates on this latter topic. For an example sensor device, calibration
parameters were established using calibration measurements of approximately 1.5
min in duration for the 3D accelerometer and 2.5 min in duration for the 3D
gyroscope. Correction of each detected 3D value using the established calibration
parameters in further measurements requires only nine addition and nine
multiplication operations.
PMID- 25123470
TI - [Craniocerebral trauma: magnetic resonance imaging of diffuse axonal injury].
AB - CLINICAL/METHODICAL ISSUE: Acceleration-deceleration rotational brain trauma is a
common cause of disability or death in young adults and often leads to a focal
destruction of axons. The resulting pathology, axonal shear injury is referred to
as diffuse axonal injury (DAI). The DAI-associated lesions occur bilaterally, are
widely dispersed and have been observed in the surface and deep white matter.
They are found near to and far from the impact site. STANDARD RADIOLOGICAL
METHODS: When DAI is clinically suspected, magnetic resonance imaging (MRI) is
the method of choice for further clarification, especially in patients where
cranial computed tomography (CT) is inconspicuous. METHODICAL INNOVATIONS: To
investigate the presence of DAI after traumatic brain injury (TBI), a multimodal
MRI approach is applied including the common structural and also functional
imaging sequences. PERFORMANCE: For structural MRI, fluid-attenuated inversion
recovery (FLAIR) weighted and susceptibility contrast imaging (SWI) are the
sequences mainly used. The SWI technique is extremely sensitive to blood
breakdown products, which appear as small signal voids at three locations, at the
gray-white interface, in the corpus callosum and in the brain stem. Functional
MRI comprises a group of constantly developing techniques that have great
potential in optimal evaluation of the white matter in patients after
craniocerebral trauma. These imaging techniques allow the visualization of
changes associated with shear injuries, such as functional impairment of axons
and decreased blood flow and abnormal metabolic activity of the brain parts
affected. ACHIEVEMENTS: The multimodal MRI approach in patients with DAI results
in a more detailed and differentiated representation of the underlying
pathophysiological changes of the injured nerve tracts and helps to improve the
diagnostic and prognostic accuracy of MRI. PRACTICAL RECOMMENDATIONS: When DAI is
suspected multimodal MRI should be performed as soon as possible after
craniocerebral injury.
PMID- 25123471
TI - Internet-based stress management for women with preterm labour--a case-based
experience report.
AB - Pregnant women with preterm labour (PTL) in pregnancy often experience increased
distress and anxieties regarding both the pregnancy and the child's health. The
pathogenesis of PTL is, among other causes, related to the stress-associated
activation of the maternal-foetal stress system. In spite of these
psychobiological associations, only a few research studies have investigated the
potential of psychological stress-reducing interventions. The following paper
will present an online anxiety and stress management self-help program for
pregnant women with PTL. Structure and content of the program will be illustrated
by a case-based experience report. L.B., 32 years (G3, P1), was recruited at
gestational week 27 while hospitalized for PTL for 3 weeks. She worked
independently through the program for 6 weeks and had regular written contact
with a therapist. Processing the program had a positive impact on L.B.'s anxiety
and stress levels, as well as on her experienced depressive symptoms and bonding
to the foetus. As PTL and the risk of PTB are associated with distress,
psychological stress-reducing interventions might be beneficial. This study
examines the applicability of an online intervention for pregnant women with PTL.
The case report illustrates how adequate low-threshold psychological support
could be provided to these women.
PMID- 25123472
TI - Use of osteoporosis medications among Turkish patients.
PMID- 25123473
TI - Correcting for the bias caused by exposure measurement error in epidemiological
studies.
AB - An important goal of many epidemiological studies is to estimate the magnitude of
association between an exposure and an outcome. Exposure measurement error causes
bias in such estimates of association and can be substantial. In this article, we
describe the problem of exposure measurement error and its effects. We show how a
simple hand calculation, in conjunction with validation study data and a
calibration equation, can be used to correct estimates for the bias caused by
exposure measurement error. Correcting estimates of association for measurement
error helps researchers appropriately assess effect size.
PMID- 25123476
TI - Tom D. Humphreys II: a pioneer of molecular embryology.
PMID- 25123474
TI - SUMO-1 plays crucial roles for spindle organization, chromosome congression, and
chromosome segregation during mouse oocyte meiotic maturation.
AB - Small ubiquitin-related modifier-1 (SUMO-1)-dependent modifications of many
target proteins are involved in a range of intracellular processes. Previous
studies reported the localization of SUMO-1 during oocyte meiosis, and that
overexpression of Sentrin/SUMO-specific protease 2 (SENP2), a de-SUMOylation
protease, altered SUMO-modified proteins, and caused defects in metaphase-II
spindle organization. In this study, we detailed the consequences of SUMO-1
mediated SUMOylation by either inhibition of SUMO-1 or UBC9 with a specific
antibody or their depletion by specific siRNA microinjection. Inhibition or
depletion of SUMO-1 or UBC9 in germinal vesicle (GV)-stage oocytes decreased the
rates of germinal vesicle breakdown and first polar body (PB1) extrusion; caused
defective spindle organization and misaligned chromosomes; and led to aneuploidy
in matured oocytes. Stage-specific antibody injections suggested that SUMO-1
functions before anaphase I during PB1 extrusion. Further experiments indicated
that the localization of gamma-tubulin was disordered after SUMO-1 inhibition,
and that SUMO-1 depletion disrupted kinetochore-microtubule attachment at
metaphase I. Moreover, SUMO-1 inhibition resulted in less-condensed chromosomes,
altered localization of REC8 and securin, and reduced BUBR1 accumulation at the
centromere. On the other hand, overexpression of SUMO-1 in GV-stage oocytes had
no significant effect on oocyte maturation. In conclusion, our results implied
that SUMO-1 plays crucial roles during oocyte meiotic maturation, specifically
involving spindle assembly and chromosome behavior, by regulating kinetochore
microtubule attachment and the localization of gamma-tubulin, BUBR1, REC8, and
securin.
PMID- 25123478
TI - Noninvasive continuous positive airway pressure delivered using a pediatric
helmet in dogs recovering from general anesthesia.
AB - OBJECTIVE: To evaluate the feasibility and efficacy of noninvasive continuous
positive airway pressure (CPAP) administered with a pediatric helmet in healthy
dogs recovering from general anesthesia. DESIGN: Randomized, cross-over, clinical
study. SETTING: University teaching hospital. ANIMALS: Fifteen healthy female,
client-owned dogs recovering from general anesthesia following elective
ovariohysterectomy. INTERVENTIONS: All dogs received the same standardized
anesthetic protocol (acepromazine, morphine, propofol, and isoflurane in oxygen).
After extubation, a pediatric helmet was placed on all dogs and connected to a
venturi valve supplied with medical air. In all patients, the gas flow was set to
50 L/minute and the FiO2 to 0.21. Dogs received the following sequence of
treatments, each lasting 20 minutes: 0 CPAP (pre-CPAP), CPAP of 5 cm H2 O (CPAP),
and again 0 CPAP (post-CPAP). MEASUREMENTS AND MAIN RESULTS: During the entire
study, the following data were collected: pressure and FiO2 inside the helmet,
mean arterial pressure, respiratory rate, heart rate, sedation score (0 = awake,
10 = deep sedation), and tolerance to the helmet (0 = excellent, 4 = poor). At
the end of each phase, an arterial blood sample was sampled. As compared with the
pre-CPAP and the post-CPAP periods, during the CPAP period, the PaCO2 , alveolar
arterial oxygen gradient (P[A-a]O2 ), and respiratory rate significantly
decreased. The PaO2 was higher at CPAP (105.6 +/- 4.0 mm Hg) compared with pre
CPAP (80.6 +/- 6.9 mm Hg) and post-CPAP (86.7 +/- 5.8 mm Hg). Tolerance and
sedation scores during the CPAP period were not different from those in the pre
CPAP and post-CPAP periods. CONCLUSIONS: Noninvasive CPAP applied through a
helmet is a feasible and effective supportive technique in dogs recovering from
general anesthesia.
PMID- 25123479
TI - Laparoscopic common bile duct exploration.
AB - BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) is a safe and
effective single-stage treatment for choledocholithiasis in the elective setting.
The outcomes after LCBDE in the emergency setting are unknown. The aim of this
study was to compare the outcomes following elective and emergency LCBDE for
choledocholithiasis. METHODS: Details of all patients who underwent LCBDE for
choledocholithiasis between August 2003 and August 2013 were analysed
retrospectively. The primary outcome measure was common bile duct (CBD) stone
clearance rate. Secondary outcome measures were conversion rate, morbidity,
mortality and length of hospital stay. RESULTS: Some 215 consecutive patients (57
male; median age 65 (range 14-92) years) underwent LCBDE. Some 121 procedures
were performed electively and 94 as an emergency. Forty-five patients (48 per
cent) presented with obstructive jaundice or cholangitis in the emergency LCBDE
group compared with 15 (12.4 per cent) in the elective group (P < 0.001). The CBD
stone clearance rate was similarly high in both groups (96 versus 96.7 per cent
respectively; P = 0.557). There were no significant differences in conversion
rate (6 versus 4.1 per cent), morbidity (5 versus 6.6 per cent), mortality (2
versus 0 per cent) or median length of stay (3 days) between groups. Two patients
died, both following emergency LCBDE. CONCLUSION: LCBDE can be performed safely
and effectively in both elective and emergency settings.
PMID- 25123480
TI - A terminal 3p26.3 deletion is not associated with dysmorphic features and
intellectual disability in a four-generation family.
AB - Terminal deletions of the distal part of the short arm of chromosome 3 cause a
wide range of phenotypes from normal to dysmorphic including microcephaly,
developmental delay and intellectual disability. We studied the clinical
consequences of a terminal deletion of the short arm of chromosome 3 in four
generations of a family. The index patient is a14-month-old boy with
microcephaly, corpus callosum dysgenesis, and minor dysmorphic features. Single
Nucleotide Polymorphism (SNP) array analysis detected a duplication on the long
arm of chromosome 6. His apparently healthy mother carries the same 6q
duplication, but as an unexpected finding a terminal deletion of 2.9 Mb of the
short arm of chromosome 3 was observed. Further co-segregation analysis in the
family for the chromosome 3 deletion showed that with the exception of the sister
of the index who has autism, speech delay, and learning problems, family members
in four generations of this family are carrier of this 3p deletion and apparently
healthy. To our knowledge, this is the first report of a study of this terminal
3p deletion in four generations. In this report, we review the literature on
terminal 3p deletions and discuss the importance of molecular testing and
reporting of copy number variants to achieve accurate genetic counseling in
prenatal and postnatal screening.
PMID- 25123482
TI - Ultrafast optical control of orbital and spin dynamics in a solid-state defect.
AB - Atom-scale defects in semiconductors are promising building blocks for quantum
devices, but our understanding of their material-dependent electronic structure,
optical interactions, and dissipation mechanisms is lacking. Using picosecond
resonant pulses of light, we study the coherent orbital and spin dynamics of a
single nitrogen-vacancy center in diamond over time scales spanning six orders of
magnitude. We develop a time-domain quantum tomography technique to precisely map
the defect's excited-state Hamiltonian and exploit the excited-state dynamics to
control its ground-state spin with optical pulses alone. These techniques
generalize to other optically addressable nanoscale spin systems and serve as
powerful tools to characterize and control spin qubits for future applications in
quantum technology.
PMID- 25123481
TI - Structural biology. Crystal structure of a CRISPR RNA-guided surveillance complex
bound to a ssDNA target.
AB - In prokaryotes, RNA derived from type I and type III CRISPR loci direct large
ribonucleoprotein complexes to destroy invading bacteriophage and plasmids. In
Escherichia coli, this 405-kilodalton complex is called Cascade. We report the
crystal structure of Cascade bound to a single-stranded DNA (ssDNA) target at a
resolution of 3.03 angstroms. The structure reveals that the CRISPR RNA and
target strands do not form a double helix but instead adopt an underwound ribbon
like structure. This noncanonical structure is facilitated by rotation of every
sixth nucleotide out of the RNA-DNA hybrid and is stabilized by the highly
interlocked organization of protein subunits. These studies provide insight into
both the assembly and the activity of this complex and suggest a mechanism to
enforce fidelity of target binding.
PMID- 25123483
TI - Prevention of muscular dystrophy in mice by CRISPR/Cas9-mediated editing of
germline DNA.
AB - Duchenne muscular dystrophy (DMD) is an inherited X-linked disease caused by
mutations in the gene encoding dystrophin, a protein required for muscle fiber
integrity. DMD is characterized by progressive muscle weakness and a shortened
life span, and there is no effective treatment. We used clustered regularly
interspaced short palindromic repeat/Cas9 (CRISPR/Cas9)-mediated genome editing
to correct the dystrophin gene (Dmd) mutation in the germ line of mdx mice, a
model for DMD, and then monitored muscle structure and function. Genome editing
produced genetically mosaic animals containing 2 to 100% correction of the Dmd
gene. The degree of muscle phenotypic rescue in mosaic mice exceeded the
efficiency of gene correction, likely reflecting an advantage of the corrected
cells and their contribution to regenerating muscle. With the anticipated
technological advances that will facilitate genome editing of postnatal somatic
cells, this strategy may one day allow correction of disease-causing mutations in
the muscle tissue of patients with DMD.
PMID- 25123485
TI - Glaciers. Attribution of global glacier mass loss to anthropogenic and natural
causes.
AB - The ongoing global glacier retreat is affecting human societies by causing sea
level rise, changing seasonal water availability, and increasing geohazards.
Melting glaciers are an icon of anthropogenic climate change. However, glacier
response times are typically decades or longer, which implies that the present
day glacier retreat is a mixed response to past and current natural climate
variability and current anthropogenic forcing. Here we show that only 25 +/- 35%
of the global glacier mass loss during the period from 1851 to 2010 is
attributable to anthropogenic causes. Nevertheless, the anthropogenic signal is
detectable with high confidence in glacier mass balance observations during 1991
to 2010, and the anthropogenic fraction of global glacier mass loss during that
period has increased to 69 +/- 24%.
PMID- 25123484
TI - A memory of errors in sensorimotor learning.
AB - The current view of motor learning suggests that when we revisit a task, the
brain recalls the motor commands it previously learned. In this view, motor
memory is a memory of motor commands, acquired through trial-and-error and
reinforcement. Here we show that the brain controls how much it is willing to
learn from the current error through a principled mechanism that depends on the
history of past errors. This suggests that the brain stores a previously unknown
form of memory, a memory of errors. A mathematical formulation of this idea
provides insights into a host of puzzling experimental data, including savings
and meta-learning, demonstrating that when we are better at a motor task, it is
partly because the brain recognizes the errors it experienced before.
PMID- 25123486
TI - Isolation and characterization of microsatellite loci for the blackstripe
topminnow Fundulus notatus and their variability in two closely related species.
AB - A total of 17 polymorphic microsatellite loci were isolated from the blackstripe
topminnow Fundulus notatus. In a sample of 29 individuals, these loci were found
to possess two to 19 alleles with expected heterozygosity values ranging from
0.212 to 0.919 and all but one of the loci conformed to Hardy-Weinberg
equilibrium expectations. Many of these loci were polymorphic in the closely
related species Fundulus olivaceus and Fundulus euryzonus providing a set of
markers that should prove useful in future ecological and evolutionary studies of
members of this species complex.
PMID- 25123487
TI - Occupational injuries in Ohio wood product manufacturing: a descriptive analysis
with emphasis on saw-related injuries and associated causes.
AB - BACKGROUND: Stationary sawing machinery is often a basic tool in the wood product
manufacturing industry and was the source for over 2,500 injury/illness events
that resulted in days away from work in 2010. METHODS: We examined 9 years of
workers' compensation claims for the state of Ohio in wood product manufacturing
with specific attention to saw-related claims. For the study period, 8,547 claims
were evaluated; from this group, 716 saw-related cases were examined. RESULTS:
The sawmills and wood preservation sub-sector experienced a 71% reduction in
average incidence rate and an 87% reduction in average lost-time incidence rate
from 2001 to 2009. The top three injury category descriptions for lost-time
incidents within saw-related claims were fracture (35.8%), open wounds (29.6%),
and amputation (14.8%). CONCLUSIONS: For saw-related injuries, preventing blade
contact remains important but securing the work piece to prevent kickback is also
important.
PMID- 25123488
TI - Generalised hyperpigmentation caused by ectopic adrenocorticotropic hormone
syndrome with recurrent thymic neuroendocrine carcinoma.
AB - Ectopic adrenocorticotropic hormone (ACTH) syndrome is a rare cause of
generalised hyperpigmentation. The clinical features are due to the excessive
ectopic secretion of adenocorticotropin by diverse neuroendocrine or non
endocrine tumours. Here, we describe a rare case of ectopic ACTH syndrome
developing from recurring thymic neuroendocrine carcinoma, which first presented
as generalised hyperpigmentation.
PMID- 25123489
TI - Minimal benefit of earlier-than-recommended repeat colonoscopy among US Medicare
enrollees following a negative colonoscopy.
AB - BACKGROUND: A large proportion of US Medicare beneficiaries undergo earlier-than
recommended follow-up colonoscopies after negative screening colonoscopy. Such
practice entails substantial cost and added risk. AIMS: To compare the risk of
colorectal cancer (CRC) associated with varying follow-up colonoscopy intervals
following a negative colonoscopy, and to determine whether the potential benefit
of a shorter colonoscopy follow-up interval would differ by gender. METHODS: We
conducted a weighted cohort study using the Surveillance, Epidemiology and End
Results-Medicare linked database (1991-2006) among 932,370 Medicare enrollees who
are representative of the entire US elderly population. We compared the
cumulative incidence of CRC among patients who underwent follow-up colonoscopies
at different intervals following a negative colonoscopy. The primary outcome was
incident CRC. RESULTS: The eligible study cohort (n = 480,864) included 106,924
patients who underwent >=1 colonoscopy. Men were more likely to require
polypectomy during their initial colonoscopy than women. Compared to the
recommended 9-10 year follow-up colonoscopy interval, an interval of 5-6 years
was associated with the largest CRC cumulative risk reduction [i.e. 0.17% (95%
CI: 0.009-0.32%)]. The magnitude of risk reduction associated with shorter
colonoscopy follow-up intervals was not significantly different between men and
women. CONCLUSIONS: Among elderly individuals who undergo a negative colonoscopy,
the magnitude of reduction in the cumulative CRC risk afforded by earlier-than
recommended follow-up colonoscopy is quite small, and probably cannot justify the
risk and cost of increased colonoscopy frequency. In addition, there are
insufficient differences between men and women to warrant gender-specific
recommendations.
PMID- 25123490
TI - Up-down asymmetry in vertical induced motion and optokinetic nystagmus.
AB - We investigated the effects of pursuit effort against the optokinetic nystagmus
(OKN) on induced motion (IM) by measuring vertical IM and eye movements.
Participants viewed an inducing stimulus (a random dot pattern) moving either
upward or downward at the velocity of 10 or 40 degrees /s. A horizontally moving
target (a single dot) was then presented within the inducing stimulus.
Participants were asked to pursue the target and report the perceived slant of
the target motion path by using a joystick. The results showed that IM magnitude
was larger with an upward stimulation than with a downward stimulation. IM
magnitude was also larger at 40 degrees /s than at 10 degrees /s. The results
of eye movements prior to the target presentation showed that OKN was elicited
more effectively with an upward stimulation than with a downward stimulation and
at 40 degrees /s than at 10 degrees /s. OKN was markedly reduced when the
target was presented within the inducing stimulus. These results support the
oculomotor theory that IM magnitude reflects pursuit effort against OKN in
response to an inducing stimulus.
PMID- 25123491
TI - Stability and binding interaction of bilirubin on a gold nano-surface: steady
state fluorescence and FT-IR investigation.
AB - A gold nanoparticle exhibits strong absorption and emission due to its unique
physical geometry and surface plasmon resonance phenomena. A further modification
with organic molecules makes it more appropriate for biological applications. The
current manuscript illustrated the optical behavior and stability of bilirubin
(BR) coated gold (AuBR) nanoparticles, using BR itself as a reducing agent. In
addition, FT-IR and steady state fluorescence measurements were performed to
illustrate the binding interaction of BR with the Au(III) ion and the
nanoparticles. BR showed a strong affinity towards Au(III) and the measured
binding constant was ~4.3 * 10(5) M(-1). It caused reduction of the Au(III) ion
and rendered the formation of cubic face centered AuBR nanoparticles, which were
~20 nm in diameter. The particles were stabilized as BR was bound to the gold
nanoparticle surface, which was confirmed by FT-IR measurement. An intense
carboxyl C=O stretching vibration at 1695 cm(-1) was observed for the BR powder
but was absent for the AuBR nanoparticles. However, two weak bands at ~1563 and
1391 cm(-1), presumably due to the asymmetric and symmetric stretching vibrations
of the carboxylate form (COO(-)), were found for the AuBR nanoparticles. A
stretching vibration of lactam C[double bond, length as m-dash]O appeared at 1645
cm(-1) for BR and the band was shifted to 1647 cm(-1) for the AuBR nanoparticles.
The stretching modes of pyrrole N-H and lactam N-H were detected at 3406 cm(-1)
and 3267 cm(-1), respectively, for BR. However, the pyrrole N-H band shifted to
3446 cm(-1) and became broader for the AuBR nanoparticles. The observed blue
shift in the lactam C[double bond, length as m-dash]O and N-H vibrations of the
AuBR nanoparticles indicated a weakening/absence of internal hydrogen bonds
between the carboxyl groups and the four N-H bonds in the BR moiety. The binding
of BR to the surface provides great stability to the nanoparticles, which
remained monodispersed in the large pH range (pH 4 to 12) for more than a month.
However, under acidic pH conditions the particles associated to form bigger
particles and the plasmon resonance band shifted as they grew; the plasmon
resonance band shifted from 525 nm (at pH 7.0) to 555 nm (at pH 3.0). The
particles also remained stable in the presence of a higher concentration of salt
(KCl and NaCl) in the dispersing media.
PMID- 25123492
TI - Effects of small airway dysfunction on the clinical expression of asthma: a focus
on asthma symptoms and bronchial hyper-responsiveness.
AB - BACKGROUND: The small airways are an important site of inflammation in asthma.
However, the relation between small airway dysfunction and clinical expression of
asthma has hardly been studied. AIM: To investigate the association of small and
large airway dysfunction with asthma symptoms and bronchial hyper-responsiveness
(BHR). METHODS: Fifty-eight patients with asthma were characterized with
spirometry, body plethysmography, impulse oscillometry, alveolar and bronchial
exhaled nitric oxide, and a methacholine provocation. Symptoms of nocturnal
asthma, exercise-related symptoms, BHR symptoms, and respiratory symptoms were
assessed with the Asthma Control Questionnaire and Bronchial Hyper-responsiveness
Questionnaire. Perception of dyspnea was rated with the Borg score during the
provocation test. RESULTS: Small and large airway dysfunction did not associate
with higher scores for nocturnal, exercise-related, or BHR symptoms. Only higher
scores on wheezing were significantly associated with higher values of difference
between R5 and R20 (R5-R20) (r = 0.367, P < 0.01) and AX (r = 0.354, P < 0.01).
Lower FEF25-75% (P = 0.024) and higher R5-R20 (P = 0.003) values were
independently associated with more severe BHR to methacholine, but not FEV1 or
R20 values. The increase in dyspnea during the methacholine provocation was
strongly and independently correlated with the decrease in FEV1 and reactance of
the respiratory system at 5 Hertz. CONCLUSION: Small and large airway dysfunction
poorly associate with asthma symptoms in our patients. However, deteriorations in
small airway dysfunction are strongly related to an increase in dyspnea during
bronchial provocation with methacholine. Small airway dysfunction contributes
also independently to the clinical expression of asthma, as reflected by the
severity of BHR.
PMID- 25123493
TI - Total syntheses of lycoposerramine-V and 5-epi-lycoposerramine-V.
AB - Enantioselective total syntheses of lycopodium alkaloids lycoposerramine-V and 5
epi-lycoposerramine-V have been accomplished. Features of the newly established
total synthesis include: 1) introduction of the first chiral center with a
scalable desymmetrization reaction of an meso-anhydride; 2) chemoselective
functionalization of a bis-Weinreb-amide with Grignard addition; and 3)
construction of the multifunctionalized cyclohexanone with a stereoselective
intramolecular Michael addition.
PMID- 25123496
TI - Binary-metal perovskites toward high-performance planar-heterojunction hybrid
solar cells.
AB - A simple, low temperature solution process for Pb/Sn binary-metal perovskite
planar-heterojunction solar cells is demonstrated. Sn inclusion substantially
influences the band-gap, crystallization kinetics, and thin-film formation
leading to a broadened light absorption and enhanced film coverage on
ITO/PEDOT:PSS. As a result, the optimized device shows a PCE exceeding 10%, which
is the best result for binary-metal perovskite solar cells so far.
PMID- 25123497
TI - Assembly of Na3V2(PO4)3 nanoparticles confined in a one-dimensional carbon sheath
for enhanced sodium-ion cathode properties.
AB - Structural and morphological control is an effective approach for improvement of
electrochemical properties in rechargeable batteries. One-dimensionally assembled
structure composed of NASICON-type Na3 V2 (PO4 )3 nanoparticles were fabricated
through an electrospinning method to meet the requirements for the development of
efficient electrode materials in Na-ion batteries. High-temperature treatment of
electrospun precursor fibers under an argon flow provides a nonwoven fabric of
nanowires comprising crystallographically oriented nanoparticles of NASICON-type
Na3 V2 (PO4 )3 within a carbon sheath. The mesostructure comprising NASICON-type
Na3 V2 (PO4 )3 and carbon give a short sodium-ion transport pass and an efficient
electron conduction pass. Electrochemical properties of NASICON-type Na3 V2 (PO4
)3 are improved on the basis of one-dimensional nanostructures designed in the
present study.
PMID- 25123494
TI - The effect of hazelnut roasted skin from different cultivars on the quality
attributes, polyphenol content and texture of fresh egg pasta.
AB - BACKGROUND: Hazelnut skin is the perisperm of the hazelnut kernel. It is
separated from the kernel during the roasting process and is normally discarded.
Recent studies have reported that hazelnut skin is a rich source of dietary fibre
as well as of natural antioxidants owing to the presence of phenolic compounds.
The aim of this study was to assess the use of hazelnut skins obtained from
different cultivars for enhancing the nutritional value of fresh egg pasta.
RESULTS: Skins obtained from roasted hazelnuts of four different varieties were
used at three concentrations as a flour replacement in fresh egg pasta. Hazelnut
skin concentration significantly influenced all evaluated physicochemical
parameters as well as consumers' appreciation for the pasta, but significant
differences were also observed between the four varieties. Although pasta
produced with 10 and 15% hazelnut skin displayed the highest content of
polyphenolic compounds and antioxidant activity in vitro, pasta containing 5%
Tombul hazelnut skin showed maximum consumer preference. CONCLUSION: The results
obtained in the present study highlighted that it is possible to use hazelnut
skin in fresh pasta production to obtain a fortified food with high fibre content
and antioxidant activity. The characteristics of the resulting pasta were
strictly correlated with the hazelnut variety used for skin production and, of
course, with the percentage of skin that was added.
PMID- 25123495
TI - Real-time assessment of possible electromagnetic-field-induced changes in protein
conformation and thermal stability.
AB - Previous studies on possible interactions of radiofrequency electromagnetic
fields (RF EMFs) with proteins have suggested that RF EMFs might affect protein
structure and folding kinetics. In this study, the isolated thermosensor protein
GrpE of the Hsp70 chaperone system of Escherichia coli was exposed to EMFs of
various frequencies and field strengths under strictly controlled conditions.
Circular dichroism spectroscopy was used to monitor possible structural changes.
Simultaneously, temperature was recorded at each point of observation. The coiled
coil part of GrpE has been reported to undergo a well-defined and fully
reversible folding/unfolding transition, thus facilitating the differentiation
between thermal and non-thermal effects of RF EMFs. Any direct effect of EMF on
the conformation and/or stability would result in a shift of the conformational
equilibrium of the protein at a given temperature. Possible immediate (t <= 0.1
s) and delayed (t >= 30 s) effects of RF EMFs were investigated with sinusoidal
signals of 0.1, 1.0, and 1.9 GHz at various field strengths up to 5.0 kV/m and
with GSM signals at 0.3 kV/m in the protein solution. Taking the overall
uncertainty of the experimental system into account, possible RF EMF-induced
shifts in the conformational equilibrium of less than 1% of its total range might
have been detected. The results obtained with the different experimental
protocols indicate, however, that the conformational equilibrium of GrpE is
insensitive to electromagnetic fields in the tested range of frequency and field
strength.
PMID- 25123498
TI - Absorbing phase transitions and dynamic freezing in running active matter
systems.
AB - We examine a two-dimensional system of sterically repulsive interacting disks
where each particle runs in a random direction. This system is equivalent to a
run-and-tumble dynamics system in the limit where the run time is infinite. At
low densities, we find a strongly fluctuating state composed of transient
clusters. Above a critical density that is well below the density at which non
active particles would crystallize, the system can organize into a drifting
quiescent or frozen state where the fluctuations are lost and large crystallites
form surrounded by a small density of individual particles. Although all the
particles are still moving, their paths form closed orbits. The average transient
time to organize into the quiescent state diverges as a power law upon
approaching the critical density from above. We compare our results to the random
organization observed for periodically sheared systems that can undergo an
absorbing transition from a fluctuating state to a dynamical non-fluctuating
state. In the random organization studies, the system organizes to a state in
which the particles no longer interact; in contrast, we find that the randomly
running active matter organizes to a strongly interacting dynamically jammed
state. We show that the transition to the frozen state is robust against a
certain range of stochastic fluctuations. We also examine the effects of adding a
small number of pinned particles to the system and find that the transition to
the frozen state shifts to significantly lower densities and arises via the
nucleation of faceted crystals centered at the obstacles.
PMID- 25123503
TI - Electronic property modification of single-walled carbon nanotubes by
encapsulation of sulfur-terminated graphene nanoribbons.
AB - The use of carbon nanotubes (CNTs) as cylindrical reactor vessels has become a
viable means for synthesizing graphene nanoribbons (GNRs). While previous studies
demonstrated that the size and edge structure of the as-produced GNRs are
strongly dependent on the diameter of the tubes and the nature of the precursor,
the atomic interactions between GNRs and surrounding CNTs and their effect on the
electronic properties of the overall system are not well understood. Here, it is
shown that the functional terminations of the GNR edges can have a strong
influence on the electronic structure of the system. Analysis of SWCNTs before
and after the insertion of sulfur-terminated GNRs suggests a metallization of the
majority of semiconducting SWCNTs. This is indicated by changes in the radial
breathing modes and the D and G band Raman features, as well as UV-vis-NIR
absorption spectra. The variation in resonance conditions of the nanotubes
following GNR insertion make direct (n,m) assignment by Raman spectroscopy
difficult. Thus, density functional theory calculations of representative
GNR/SWCNT systems are performed. The results confirm significant changes in the
band structure, including the development of a metallic state in the
semiconducting SWCNTs due to sulfur/tube interactions. The GNR-induced
metallization of semiconducting SWCNTs may offer a means of controlling the
electronic properties of bulk CNT samples and eliminate the need for a physical
separation of semiconducting and metallic tubes.
PMID- 25123499
TI - Implications of a suspicious afirma test result in thyroid fine-needle aspiration
cytology: an institutional experience.
AB - BACKGROUND: Fine-needle aspiration (FNA) biopsy is the most frequently used
method for thyroid nodule evaluation. However, up to 30% of cases are considered
indeterminate. Surgery is typically recommended for these cases, but up to two
thirds of indeterminate cases are found to be benign. The Afirma test is used for
the preoperative classification of thyroid nodules with indeterminate cytology.
This study reviews the authors' institutional experience with Afirma. METHODS: A
cohort of 132 cases of thyroid FNA with Afirma testing was selected from the
study files and relevant information was recorded and analyzed. At the study
institution, Afirma is mainly performed on atypia of undetermined significance
(AUS)/follicular lesion of undetermined significance (FLUS) cases when diagnosed
as such on repeat FNA. RESULTS: The cohort included 98 female (74%) and 34 male
(26%) patients. Cytology diagnosis was AUS/FLUS in 68 cases (51.5%), follicular
neoplasm (FN) in 39 cases (29.5%), and FN with oncocytic features (FNOF) in 25
cases (19.0%). Of the FNOF cases with suspicious Afirma findings, 2 (15%) were
malignant and 11 (85%) were benign. Of the FN cases with suspicious Afirma
findings, 9 (53%) were malignant and 8 (47%) were benign. Of the AUS/FLUS cases
with suspicious Afirma findings, 10 (63%) were malignant and 6 (37%) were benign.
CONCLUSIONS: The Afirma classifier is a useful tool to aid in the distinction of
cytologically indeterminate nodules. Performing Afirma in cases diagnosed as
AUS/FLUS on repeat FNA would increase the positive predictive value, thereby
minimizing the number of benign cases referred to surgery. Results of the Afirma
test could be limited in cases diagnosed as FNOF.
PMID- 25123504
TI - The role of hepatic artery lymph node in pancreatic adenocarcinoma: prognostic
factor or a selection criterion for surgery.
AB - BACKGROUND: Hepatic artery lymph node (HALN) metastasis in pancreatic
adenocarcinoma reportedly confers a survival disadvantage. This has led some
authors to propose it as an indicator against pancreaticoduodenectomy (PD).
METHODS: Consecutive patients who underwent PD during 2002-2012 were identified
from the University of Louisville prospective hepatopancreaticobiliary database.
Overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan
Meier analysis. The log-rank test and multivariate Cox proportional hazards
regression were used in further analyses. RESULTS: A total of 420 patients
underwent PD during the period of study, of whom 197 had lymph node (LN)
metastasis. Among these, 41 (20.8%) patients had disease-positive HALNs. The HALN
was the only site of LN metastasis in only three of the 247 patients (1.2%).
Median follow-up was 18.5 months (interquartile range: 4.1-28.2 months). Median
OS and DFS were 22.7 months [95% confidence interval (CI) 19.0-26.3] and 12.6
months (95% CI 10.2-15.2). There was no significant difference in median OS
between HALN-positive patients (18.4 months, 95% CI 12.3-24.0) and HALN-negative
patients (19.7 months, 95% CI 16.7-22.6) (P = 0.659). On multivariate analysis,
the hazard ratio (HR) of death was highest among patients with an LN ratio of
>0.2 (HR 1.2, 95% CI 1.1-1.29; P = 0.012) followed by those with poorly
differentiated histology (HR 1.09, 95% CI 1.04-1.11; P = 0.029). CONCLUSIONS: In
pancreatic adenocarcinoma patients with LN disease, survival after PD is
comparable regardless of HALN status. Therefore, HALN-positive disease should not
preclude the performance of PD.
PMID- 25123505
TI - Expression of TNF-alpha and CD44 is implicated in poor prognosis, cancer cell
invasion, metastasis and resistance to the sunitinib treatment in clear cell
renal cell carcinomas.
AB - Tumor necrosis factor-alpha (TNF-alpha) is involved in epithelial-mesenchymal
transition (EMT) and expression of CD44, a cancer stem cell marker, in several
cancers. This study was performed to clarify the significance of TNF-alpha and
CD44 in clear cell renal cell carcinomas (ccRCCs). Expression of TNF-alpha and
CD44 was examined by immunohistochemistry in 120 ccRCCs. Involvement of TNF-alpha
in EMT and induction of CD44 was analyzed by monitoring expression of EMT-related
genes and CD44, and invasion in cultured ccRCC cell lines. TNF-alpha and CD44
were immunolocalized mainly to carcinoma cells of high-grade ccRCCs with positive
correlations with primary tumor stage. A positive correlation was also obtained
between TNF-alpha and CD44 expression, and co-upregulation of TNF-alpha and CD44
was associated with primary tumor stage, distant metastasis, and poor prognosis.
TNF-alpha enhanced migration and invasion of ccRCC cells together with down
regulation of E-cadherin expression and up-regulation of matrix metalloproteinase
9 and CD44 expression. TNF-alpha also up-regulated the expression of TNF-alpha
itself in ccRCC cells. Among the 25 ccRCC patients treated with sunitinib for
metastatic disease, high CD44 expression was associated with poor treatment
outcome. Importantly, residual carcinoma cells in the sunitinib-treated
metastatic ccRCCs were strongly positive for CD44, and the CD44 expression was
significantly higher in the tumors from the sunitinib-treated patients than in
those from untreated ones. Our data show that TNF-alpha plays an important role
in progression of ccRCCs by inducing EMT and CD44 expression, and suggest that
CD44 induced by TNF-alpha may be involved in the resistance to the sunitinib
treatment.
PMID- 25123506
TI - Safety assessment of jumps in ski racing.
AB - The influence of important parameters on the flight trajectory for jumps in
downhill World Cup races was investigated. To quantify the impact injury risk at
landing, the parameter equivalent landing height (ELH) was introduced, which
considered a variable slope inclination during the landing movement. Altogether,
145 runs at four different jumps in World Cup races and trainings were recorded
and analyzed. A simulation model was developed to predict the flight phase of the
skier. Drag and lift areas were selected by parameter identification to fit the
simulation trajectory to the two-dimensional data from the video analysis. The
maximum values of the ELH which can be absorbed with muscle force was taken from
the study of Minetti et al. for elite female and male ski racers. A sensitivity
analysis based on the four jumps showed that ELH is mainly influenced by takeoff
angle, takeoff speed, and the steepness of the landing surface. With the help of
the developed simulation software, it should be possible to predict the ELH for
jumps in advance. In case of an excessive ELH, improvements can be made by
changing the takeoff inclination or the approach speed.
PMID- 25123507
TI - Adaptation in tunably rugged fitness landscapes: the rough Mount Fuji model.
AB - Much of the current theory of adaptation is based on Gillespie's mutational
landscape model (MLM), which assumes that the fitness values of genotypes linked
by single mutational steps are independent random variables. On the other hand, a
growing body of empirical evidence shows that real fitness landscapes, while
possessing a considerable amount of ruggedness, are smoother than predicted by
the MLM. In the present article we propose and analyze a simple fitness landscape
model with tunable ruggedness based on the rough Mount Fuji (RMF) model
originally introduced by Aita et al. in the context of protein evolution. We
provide a comprehensive collection of results pertaining to the topographical
structure of RMF landscapes, including explicit formulas for the expected number
of local fitness maxima, the location of the global peak, and the fitness
correlation function. The statistics of single and multiple adaptive steps on the
RMF landscape are explored mainly through simulations, and the results are
compared to the known behavior in the MLM model. Finally, we show that the RMF
model can explain the large number of second-step mutations observed on a highly
fit first-step background in a recent evolution experiment with a microvirid
bacteriophage.
PMID- 25123509
TI - Hydrogen sulfide is essential for Schwann cell responses to peripheral nerve
injury.
AB - Hydrogen sulfide (H2 S) functions as a physiological gas transmitter in both
normal and pathophysiological cellular events. H2 S is produced from substances
by three enzymes: cystathionine beta-synthase (CBS), cystathionine gamma-lyase
(CSE), and 3-mercaptopyruvate sulfurtransferase (MST). In human tissues, these
enzymes are involved in tissue-specific biochemical pathways for H2 S production.
For example, CBS and cysteine aminotransferase/MST are present in the brain, but
CSE is not. Thus, we examined the expression of H2 S production-related enzymes
in peripheral nerves. Here, we found that CSE and MST/cysteine aminotransferase,
but not CBS, were present in normal peripheral nerves. In addition, injured
sciatic nerves in vivo up-regulated CSE in Schwann cells during Wallerian
degeneration (WD); however, CSE was not up-regulated in peripheral axons. Using
an ex vivo sciatic nerve explant culture, we found that the inhibition of H2 S
production broadly prevented the process of nerve degeneration, including myelin
fragmentation, axonal degradation, Schwann cell dedifferentiation, and Schwann
cell proliferation in vitro and in vivo. Thus, these results indicate that H2 S
signaling is essential for Schwann cell responses to peripheral nerve injury.
Hydrogen sulfide (H2 S) functions as a physiological gas transmitter in both
normal and pathophysiological cellular events. H2 S is produced from
cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE), and 3
mercaptopyruvate sulfur transferase (MST). Here, we found that CSE and MST/CAT
were present in normal peripheral nerves. Injured static nerves in vivo up
regulated CSE in Schwann cells during Wallerian degeneration, but CSE was not up
regulated in peripheral axons.
PMID- 25123508
TI - The switch from fermentation to respiration in Saccharomyces cerevisiae is
regulated by the Ert1 transcriptional activator/repressor.
AB - In the yeast Saccharomyces cerevisiae, fermentation is the major pathway for
energy production, even under aerobic conditions. However, when glucose becomes
scarce, ethanol produced during fermentation is used as a carbon source,
requiring a shift to respiration. This adaptation results in massive
reprogramming of gene expression. Increased expression of genes for
gluconeogenesis and the glyoxylate cycle is observed upon a shift to ethanol and,
conversely, expression of some fermentation genes is reduced. The zinc cluster
proteins Cat8, Sip4, and Rds2, as well as Adr1, have been shown to mediate this
reprogramming of gene expression. In this study, we have characterized the gene
YBR239C encoding a putative zinc cluster protein and it was named ERT1 (ethanol
regulated transcription factor 1). ChIP-chip analysis showed that Ert1 binds to a
limited number of targets in the presence of glucose. The strongest enrichment
was observed at the promoter of PCK1 encoding an important gluconeogenic enzyme.
With ethanol as the carbon source, enrichment was observed with many additional
genes involved in gluconeogenesis and mitochondrial function. Use of lacZ
reporters and quantitative RT-PCR analyses demonstrated that Ert1 regulates
expression of its target genes in a manner that is highly redundant with other
regulators of gluconeogenesis. Interestingly, in the presence of ethanol, Ert1 is
a repressor of PDC1 encoding an important enzyme for fermentation. We also show
that Ert1 binds directly to the PCK1 and PDC1 promoters. In summary, Ert1 is a
novel factor involved in the regulation of gluconeogenesis as well as a key
fermentation gene.
PMID- 25123511
TI - Arthroscopy versus arthrocentesis in the management of internal derangement of
the temporomandibular joint: a systematic review and meta-analysis.
AB - The aim of this study was to assess whether arthroscopy or arthrocentesis is most
effective and feasible in the management of internal derangement of the
temporomandibular joint (TMJ), specifically in relation to joint movement and
pain. A comprehensive electronic search without date or language restrictions was
performed in January 2014. Inclusion criteria were the following: study in
humans; randomized or quasi-randomized controlled trials (RCTs), controlled
clinical trials (CCTs), and retrospective studies; comparison of arthrocentesis
and arthroscopy in the treatment of internal derangement. Six publications were
included in the review, two RCTs, two CCTs, and two retrospective studies. Two
studies showed a low risk of bias and four studies showed a moderate risk of
bias. There were statistically significant differences between arthrocentesis and
arthroscopy with regard to maximal inter-incisal opening and pain reduction, but
no difference between the two groups for postoperative complications. The results
of this meta-analysis on the management of internal derangement of the TMJ
revealed arthroscopy to have superior efficacy to arthrocentesis in increasing
joint movement and decreasing pain. Both arthroscopy and arthrocentesis have
comparable postoperative complication rates. However, the current meta-analysis
is incomplete due to the paucity of good quality studies in the high-impact, peer
reviewed literature; therefore, further better-designed studies are required to
address this important question before final conclusions can be drawn as to the
true comparative outcomes of TMJ arthrocentesis versus TMJ arthroscopy.
PMID- 25123510
TI - Enhancing radiotherapy by lipid nanocapsule-mediated delivery of amphiphilic gold
nanoparticles to intracellular membranes.
AB - Amphiphilic gold nanoparticles (amph-NPs), composed of gold cores surrounded by
an amphiphilic mixed organic ligand shell, are capable of embedding within and
traversing lipid membranes. Here we describe a strategy using crosslink
stabilized lipid nanocapsules (NCs) as carriers to transport such membrane
penetrating particles into tumor cells and promote their transfer to
intracellular membranes for enhanced radiotherapy of cancer. We synthesized and
characterized interbilayer-crosslinked multilamellar lipid vesicles (ICMVs)
carrying amph-NPs embedded in the capsule walls, forming Au-NCs. Confocal and
electron microscopies revealed that the intracellular distribution of amph-NPs
within melanoma and breast tumor cells following uptake of free particles vs Au
NCs was quite distinct and that amph-NPs initially delivered into endosomes by Au
NCs transferred over a period of hours to intracellular membranes through tumor
cells, with greater intracellular spread in melanoma cells than breast carcinoma
cells. Clonogenic assays revealed that Au-NCs enhanced radiotherapeutic killing
of melanoma cells. Thus, multilamellar lipid capsules may serve as an effective
carrier to deliver amphiphilic gold nanoparticles to tumors, where the membrane
penetrating properties of these materials can significantly enhance the efficacy
of frontline radiotherapy treatments.
PMID- 25123512
TI - Transcriptionist saturation: knowing too much about sensitive health and social
data.
AB - AIM: The paper describes and interprets the experiences of transcriptionists
employed to translate recorded auditory research, medical, court data into text
and specifically when the research is sensitive and the audio source material may
be traumatic to hear. BACKGROUND: This study highlights the ongoing need for
transcriptionists to be recognized in the ethics process as a potentially
vulnerable group who need greater support and debriefing when transcribing
sensitive health and social data. DESIGN: Qualitative research. METHODS:
Telephone interviews were conducted with 12 transcriptionists in Australia and
New Zealand during 2012, who had transcribed sensitive material and reported
issues with transcribing certain topics. Accuracy and confidentiality were
paramount in this work. FINDINGS: Seven participants reported negative emotional
and physical effects from transcribing sensitive material On the other hand six
participants found the work enjoyable. CONCLUSION: The majority of the
transcriptionists did not receive any debriefing after transcribing sensitive
material. The participants developed their own strategies to deal with the
effects of transcribing sensitive materials such as online support groups,
relaxation activities and unofficial debriefing with friends and family.
PMID- 25123513
TI - Viewing rate and reproducibility of papillary muscle areas in foetal
atrioventricular valves using spatio-temporal image correlation in the rendering
mode in congenital heart disease.
AB - OBJECTIVE: To assess the viewing rate and reproducibility of areas of the
papillary muscles (PMs) of foetal atrioventricular valves using spatio-temporal
image correlation (STIC) in the rendering mode in congenital heart disease (CHD).
METHODS: We retrospectively reviewed 40 4D-STIC volume datasets from different
foetal CHD cases at a gestational age of 18w6d-35w6d. The following papillary
muscles (PMs) were assessed: antero-lateral (MPAL) and postero-medial (MPPM) to
the mitral valve and antero-superior (MPAS), inferior (MPI) and septal (MPS) to
the tricuspid valve. To assess the valve viewing rate, percentages (%) were used.
The concordance correlation coefficient (CCC) was used to assess inter-observer
reliability. RESULTS: Two independent observers concluded that a complete
examination of the PMs was impossible in 11 cases, yielding a viewing rate of
72.5%. The complete examination of the PMs of the tricuspid and mitral valves was
possible by both examiners in 33/40 (82.5%) and 32/40 (80.0%) cases,
respectively. We observed moderate to good inter-observer reliability with CCCs
of 0.95, 0.92, 0.97, 0.96 and 0.97 for MPS, MPI, MPAS, MPAL and MPPM,
respectively. CONCLUSION: The viewing rate of PM areas in different CHDs using
STIC in the rendering mode was moderate. The inter-observer reproducibility was
moderate to good for all PM areas.
PMID- 25123514
TI - Can measurement of cervical length, fetal head position and posterior cervical
angle be an alternative method to Bishop score in the prediction of successful
labor induction?
AB - Abstract Aim: The purpose of this study was to evaluate sonographic cervical
length, posterior cervical angle and fetal head position in predicting successful
induction of labor at term can be an alternative method to Bishop score. Methods:
This prospective observational study recruited 223 women with singleton
gestations scheduled for induction of labor at 37-42 weeks. Parity, body mass
index, Bishop score, fetal head position, cervical angle measurement and cervical
length was investigated to predict successful labor induction. Multiple
regression analysis was performed to determine the parameters in the prediction
of successful vaginal delivery within 24 hours. Results: Forty-five patients were
excluded because of cesarean section performed for other reasons than arrest of
dilation or fetal head descent (43 fetal distress, 2 cord prolapsus). Remaining
178 patients were divided into two groups according to duration of delivery time.
139 patients delivered within 24 hours were classified as group I, 39 patients
delivered after 24 hours were classified as group II. Percentage of multiparity
was statistically significantly higher in group I than in group II [59 (42.4%), 9
(23.0%) respectively, p = 0.009]. Cervical length was statistically significantly
shorter in group I than in group II [23.1 +/- 7.42 mm, 31.3 +/- 6.83 mm
respectively, p < 0.001]. Bishop score was statistically significantly higher in
group I than in group II [3 (1-4), 1 (1-4) respectively, p < 0.001]. Posterior
cervical angle was statistically significantly higher in group I than in group II
[100.1 +/- 17.2, 92.7 +/- 21.4 respectively, p = 0.007]. According to the fetal
head position, there was no statistically significant difference in labor
duration between the groups (p = 0.787). In the multivariate regression analysis
of variables, multiparity, cervical length and Bishop score were statistically
significantly predictive in successful labor induction. Conclusion: Multiparity
status, cervical length, posterior cervical angle and Bishop score can predict
successful labor induction, but fetal head position is not predictive in
successful labor induction.
PMID- 25123516
TI - The effect of a 25-hour fast during the Day of Atonement on preterm delivery.
AB - OBJECTIVE: To determine the effect of the Day of Atonement fast (a 25-hour Jewish
fast), on preterm delivery. METHODS: A comprehensive analysis of all deliveries
during the Day of Atonement and during the corresponding day a week earlier,
between the years 1988 and 2011, was performed. Preterm delivery was defined as
delivery before 37 completed weeks of gestation. Data on fasting status was
deduced from the ethnicity (as only Jewish parturients fast during the Day of
Atonement). Multivariable logistic regression model was used to control for
confounders. RESULTS: During the Day of Atonement in the studied period, 744
deliveries took place, out of which 52.1% (n = 388) were of Jewish patients (i.e.
fasting group), and 47.9% (n = 357) were of non-Jewish patients. Out these, 6.3%
(n = 47) were preterm deliveries. Jewish parturients were at significantly higher
risk for preterm delivery during the Day of Atonement (adjusted OR = 2.0; 95% CI,
1.03-3.83; p = 0.041). In the corresponding day, a week before the Day of
Atonement, Jewish ethnicity was not found to be a risk factor for preterm
delivery (OR = 0.92; 95% CI, 0.50-1.69; p = 0.789). The model controlled for:
previous preterm delivery, intrauterine growth restriction and placental
abruption. CONCLUSIONS: A 25-hour fast is an independent risk factor for preterm
delivery.
PMID- 25123517
TI - A comparison between electrical uterine monitor, tocodynamometer and intra
uterine pressure catheter for uterine activity in labor.
AB - OBJECTIVE: We aimed to evaluate the performance of a non-invasive EMG electrical
uterine monitor (EUM) versus tocodynamometry (TOCO) by comparing both to internal
uterine pressure catheter (IUPC). STUDY DESIGN: Prospective observational trial.
Uterine activity was recorded continuously and simultaneously, in women during
active term labor, with TOCO, EUM and IUPC. Uterine activity tracings were
analyzed by three blinded physicians. RESULTS: Overall, 385 tracings from 43
women were analyzed. A similar rate of interpretable tracings between physicians
was demonstrated for EUM (87%; 95% CI 80.9-92.7%) and IUPC (94.8%; 95% CI 83.4
96.3%), with a significantly lower rate for TOCO (67.5%; 95% CI 59.4-76.8%, p <
0.001). There is a significant difference in the contraction frequency for EUM
versus IUPC (0.77 +/- 2.3) compared to TOCO versus IUPC (-3.34 +/- 4.97). There
is a high variability between the timing of TOCO contractions as compared to IUPC
(4.74 +/- 10.03 seconds), while a gap of 8.46 +/- 4.24 seconds was detected for
EUM. The sensitivity, positive predictive value and false positive rate for
individual contraction identification by TOCO and EUM are 54.0%, 84.4%, 15.6% and
94.2%, 87.6%, 12.4%, respectively. CONCLUSION: EUM is efficient as IUPC for
uterine activity assessment and both techniques are superior in comparison to
external tocodynamometry. Our results support the use of non-invasive EMG
technology to monitor uterine activity.
PMID- 25123518
TI - Brain stem/brain stem occipital bone ratio and the four-line view in nuchal
translucency images of fetuses with open spina bifida.
AB - Abstract Objective: Brain stem depth/brain stem occipital bone distance (BS/BSOB
ratio) and the four-line view, in images obtained for nuchal translucency (NT)
screening in fetuses with open spina bifida (OSB). Methods: Single center,
retrospective study based on the assessment of NT screening images of fetuses
with OSB. A ratio between the BS depth and the BSOB distance was calculated
(BS/BSOB ratio) and the four-line view observed, and the sensitivity for a
BS/BSOB ratio superior/equal to 1, and for the lack of detection of the four-line
view were calculated. Results: There were 17 cases of prenatal diagnosis OSB. In
six cases, the suspicion on OSB was raised during NT screening, in six cases, the
diagnosis was made before 20 weeks and in five cases during anomaly scan. The
BS/BSOB ratio was superior/equal to 1 in all 17 cases, and three lines, were
visualized in 15/17 images of the OSB cases, being the sensitivity 100% (95% CI,
81 to 100%) and 88% (95% CI, 65 to 96%). Conclusion: Assessment of BS/BSOB ratio
and four-line view in NT images is feasible detecting affected by OSB with high
sensitivity. The presence of associated anomalies or of an enlarged NT enhances
the early detection.
PMID- 25123520
TI - Perinatal outcomes from the use of antiepileptic drugs during pregnancy: a case
control study.
AB - OBJECTIVE: To evaluate the perinatal results from epileptic women using
antiepileptic drugs during prenatal care. METHODS: This was a retrospective
longitudinal study assessing the perinatal results of women exposed to
antiepileptic drugs during pregnancy, and we compared these results with those of
pregnant women who were not exposed. The development of pregnancy, gestational
age at delivery, Apgar scores, biometric data, morbidity, stillbirths and
neonatal mortality were analyzed. The chi-square test and Fisher's exact test
were used for the categorical variables, while Student's t-test was used for
independent numerical variables. RESULTS: Over a 10-year period, 12 790 singleton
gestations were analyzed, among which 104 (0.8%) consisted of epileptic pregnant
women. From this total, 82 evolved to childbirth and their neonatal data were
compared with those of 316 newborns from non-epileptic women. The most-used
antiepileptic drug was phenobarbital in 70% of the cases. There was greater
neonatal mortality (p = 0.006), occurrence of neonatal hemorrhagic disorders (p =
0.005), and occurrence of minor congenital anomalies (p = 0.03) among the
children of women exposed to antiepileptic drugs. CONCLUSION: The antenatal
exposure to antiepileptic drugs is associated mainly with occurrences of
hemorrhagic complications during the neonatal period; furthermore, great
prevalence of newborns presenting minor congenital anomalies and elevated risk of
neonatal mortality.
PMID- 25123519
TI - Antenatal brain injury in third trimester neonates with severe congenital
anomalies: an autopsy study.
AB - OBJECTIVE: With advances in therapy, more neonates with severe congenital
anomalies are surviving, albeit some with neurologic disorders, possibly related
to antenatal low brain blood flow. This autopsy series reports antenatal brain
injury in neonates expiring due to severe anomalies, and provides correlation
with umbilical cord blood gas and acid-base analysis. METHODS: We identified
autopsies of third trimester neonates expiring shortly following delivery due to
severe anomalies or malformations. Brain injury classified as "older" included
periventricular leukomalacia, gliosis and karyorrhectic neurons, and "recent"
included red neurons and reactive glial changes. RESULTS: We identified 22 cases
(nine term, 13 preterm). 16 (73%) had brain injury, including 11 with older
injury. Cord arterial blood was analyzed in 17, and six had pH <7 or base deficit
>12 mmol/L. Four out of 5 (80%) neonates with neuronal necrosis compared to two
out of 12 (17%) without had a pH <7 or base deficit >12 mmol/L (p = 0.03). Five
out of nine (56%) neonates with white matter injury compared to one out of 8
(13%) without had pH <7 or base deficit >12 mmol/L (p = NS). CONCLUSIONS:
Antenatal brain injury is frequent in neonates with severe congenital anomalies.
Severely abnormal cord blood analysis results correlate significantly with
neuronal necrosis and show a trend toward white matter injury; however, the
absence of these abnormal results does not preclude the presence of brain injury.
PMID- 25123521
TI - Inhibition of Na(+),K(+)-ATPase in the hypothalamus, pons and cerebellum of the
offspring rat due to experimentally-induced maternal hypothyroidism.
AB - Neurodevelopment is known to be particularly susceptible to thyroid hormone
insufficiency and can result in extensive structural and functional deficits
within the central nervous system (CNS), subsequently leading to the
establishment of cognitive impairment and neuropsychiatric symptomatology. The
current study evaluated the effects of gestational and/or lactational maternal
exposure to propylthiouracil (PTU)-induced hypothyroidism (as a suggestive
multilevel experimental approach to the study of hypothyroidism-induced changes
that has been developed and characterized by the authors) on crucial brain enzyme
activities of 21-day-old Wistar rat offspring in a CNS region-specific manner.
The activities of acetylcholinesterase (AChE), Na(+),K(+)-ATPase and Mg(2+)
ATPase in the offspring hypothalamus, cerebellum and pons were assessed. The
study demonstrated that maternal exposure to PTU (0.05% w/v in the drinking
water) during the critical periods of neurodevelopment can result in an
inhibition of hypothalamic, pontine and cerebellar Na(+),K(+)-ATPase; a major
marker of neuronal excitability and metabolic energy production as well as an
important regulator of important systems of neurotransmission. On the other hand,
no significant changes in the activities of the herein offspring CNS regions'
AChE and Mg(2+)-ATPase were recorded. The observed Na(+),K(+)-ATPase inhibition:
(i) is region-specific (and non-detectable in whole brain homogenetes), (ii)
could constitute a central event in the pathophysiology of clinically-relevant
hypothyroidism-associated developmental neurotoxicity, (iii) occurs under all
examined experimental schemes, and (iv) certainly deserves further clarification
at a molecular and histopathological level. As these findings are analyzed and
compared to the available literature, they also underline the need for the
adoption and further study of Na(+),K(+)-ATPase activity as a consistent
neurochemical marker within the context of a systematic comparative study of
existing (and novel) simulation approaches to congenital and early age
hypothyroidism.
PMID- 25123522
TI - Use of magnetic resonance imaging in detecting subclinical synovitis in
rheumatoid arthritis and correlation of imaging findings with interleukin-18
levels.
AB - AIM: We studied the usefulness of magnetic resonance imaging (MRI) in detecting
subclinical inflammation in patients with asymptomatic RA and tested the
hypothesis of interleukin (IL)-18 as a marker of disease activity. METHODS:
Thirteen RA patients with Disease Activity Score of 28 joints (DAS28) < 2.6 were
evaluated. The patients underwent clinical evaluation, laboratory tests and MRI
assessment. Imaging of bilateral hands and wrists was performed using validated
acquisition and scoring techniques. Serum IL-18 levels were concurrently
measured. RESULTS: MRI assessments showed that 92.3% and 76.9% of patients had
synovitis and bone marrow edema, respectively, despite being in clinical
remission. Eight out of 12 patients (66.7%) had erosions on MRI which were not
visualised on plain radiographs. Of all the 182 joints studied for synovitis on
MRI, only one had clinical evidence of joint swelling. Comparison of the total
sum scores of synovitis between the right and left hand and wrist joints of
individual patients showed a significant difference between the two sides.
Measurements of IL-18 indicated that a large proportion (54%) of the patients had
undetectable or very low levels of the cytokine. CONCLUSION: MRI is more
sensitive in detecting erosions compared with X-rays, and is superior in its
ability to detect subclinical inflammation in RA patients. Despite being in
clinical remission, a large majority of patients had imaging-detected synovitis
and bone marrow edema. Our study highlights the usefulness of MRI for the
accurate evaluation of disease activity. In the utility of MRI, it may be
important to assess bilateral hands and wrists, instead of limiting to the
dominant side.
PMID- 25123523
TI - Degradation and mineralization of organic UV absorber compound 2
phenylbenzimidazole-5-sulfonic acid (PBSA) using UV-254nm/H2O2.
AB - Various studies have revealed the non-biodegradable and endocrine disrupting
properties of sulfonated organic UV absorbers, directing people's attention
toward their risks on ecological and human health and hence their removal from
water. In this study, UV-254nm/H2O2 advanced oxidation process (AOP) was
investigated for degrading a model UV absorber compound 2-phenylbenzimidazole-5
sulfonic acid (PBSA) and a structurally similar compound 1H-benzimidazole-2
sulfonic acid (BSA), with a specific focus on their mineralization. At 4.0mM
[H2O2]0, a complete removal of 40.0MUM parent PBSA and 25% decrease in TOC were
achieved with 190min of UV irradiation; SO4(2-) was formed and reached its
maximum level while the release of nitrogen as NH4(+) was much lower (around 50%)
at 190min. Sulfate removal was strongly enhanced by increasing [H2O2]0 in the
range of 0-4.0mM, with slight inhibition in 4.0-12.0mM. Faster and earlier
ammonia formation was observed at higher [H2O2]0. The presence of Br(-) slowed
down the degradation and mineralization of both compounds while a negligible
effect on the degradation was observed in the presence of Cl(-). Our study
provides important technical and fundamental results on the HO based degradation
and mineralization of SO3H and N-containing UV absorber compounds.
PMID- 25123524
TI - Differentiation of histoplasma and cryptococcus in cytology smears: a diagnostic
dilemma in severely necrotic cases.
AB - OBJECTIVE: The correct identification of fungal organisms is important for the
appropriate clinical management of patients. It becomes difficult in necrotic
smears when the tissue response is not clearly discernible. It is difficult to
distinguish between histoplasma and cryptococcus in severely necrotic cases,
where both appear as variably sized clear refractile haloes. METHODS: Four cases
of adrenal necrotic histoplasma infection were studied and the morphology was
compared with that of non-necrotic histoplasmosis and cases of cryptococcal
infection. Eleven cases were analysed in fine needle aspiration cytology (FNAC)
smears. Ziehl-Neelsen (ZN) stain was performed to exclude tuberculosis in
necrotic smears. A clinical and serology correlation was performed where
available. RESULTS: Necrotic cases of histoplasma infection revealed negative
refractile clear haloes similar to those of cryptococcus. Histoplasma showed
methylene blue-stained organisms in ZN stains, whereas the cryptococcus cases
were negative. Similar methylene blue-stained organisms were seen in non-necrotic
histoplasma infection. CONCLUSION: As a result of morphological overlap between
cryptococcus and histoplasma, the distinction between the two fungi can be
difficult in many cases. ZN staining appears to have a role in the
differentiation of these fungi in severely necrotic cases. This observation needs
to be validated on a larger number of cases with complete correlation with
clinical, serology and treatment records.
PMID- 25123525
TI - Child marriage and its associations with controlling behaviors and spousal
violence against adolescent and young women in Pakistan.
AB - PURPOSE: Child marriage (before 18 years) is widely prevalent in Pakistan, and
disproportionately affects young girls in rural, low-income, and poorly educated
households. Our study aims to determine the associations between child marriage
and controlling behaviors (CB) and spousal violence by husbands against
adolescent and young women in Pakistan beyond those attributed to social
vulnerabilities. METHODS: We analyzed data from the Pakistan Demographic and
Health Survey, 2012-2013, of currently married women aged 15-24 years who had
participated in the domestic violence module (n = 589, 22.5% [589/2,615] of the
subsample aged 15-24 years) to identify differences in CB and spousal violence
experiences between early (<18 years) and adult (>=18 years) ages at marriage.
Associations between child marriage and CB and spousal violence by husband were
assessed by calculating adjusted odds ratios (AOR) using logistic regression
models after controlling for demographics, social equity indicators (education,
wealth index, and rural residence), spousal age gap, and husband's education.
RESULTS: Overall, 47.8% of currently married women aged 15-24 years in Pakistan
were married before the age of 18 years. About one third of women aged 15-24
years in Pakistan reported experiencing CB (31.8%) and spousal violence (31.1%)
by their husbands. Compared with adult marriage, child marriage was significantly
associated with CB (AOR = 1.50; 95% confidence interval [CI], 1.042-2.157), any
form of spousal violence (physical or emotional) (AOR = 2.03; 95% CI, 1.392
2.969), emotional violence (AOR = 1.86; 95% CI, 1.254-2.767), and physical
violence (AOR = 2.44; 95% CI, 1.582-3.760), including severe physical violence
(AOR = 2.57; 95% CI, 1.122-5.872). CONCLUSIONS: Effective interventions are
needed to prevent child marriages and raise awareness about their negative
consequences, with special reference to spousal violence.
PMID- 25123515
TI - Sterile intra-amniotic inflammation in asymptomatic patients with a sonographic
short cervix: prevalence and clinical significance.
AB - Abstract Objective: To determine the frequency and clinical significance of
sterile and microbial-associated intra-amniotic inflammation in asymptomatic
patients with a sonographic short cervix. Methods: Amniotic fluid (AF) samples
obtained by transabdominal amniocentesis from 231 asymptomatic women with a
sonographic short cervix [cervical length (CL) <=25 mm] were analyzed using
cultivation techniques (for aerobic and anaerobic as well as genital mycoplasmas)
and broad-range polymerase chain reaction (PCR) coupled with electrospray
ionization mass spectrometry (PCR/ESI-MS). The frequency and magnitude of intra
amniotic inflammation [defined as an AF interleukin (IL)-6 concentration >=2.6
ng/mL], acute histologic placental inflammation, spontaneous preterm delivery
(sPTD), and the amniocentesis-to-delivery interval were examined according to the
results of AF cultures, PCR/ESI-MS and AF IL-6 concentrations. Results: Ten
percent (24/231) of patients with a sonographic short cervix had sterile intra
amniotic inflammation (an elevated AF IL-6 concentration without evidence of
microorganisms using cultivation and molecular methods). Sterile intra-amniotic
inflammation was significantly more frequent than microbial-associated intra
amniotic inflammation [10.4% (24/231) versus 2.2% (5/231); p < 0.001]. Patients
with sterile intra-amniotic inflammation had a significantly higher rate of sPTD
<34 weeks of gestation [70.8% (17/24) versus 31.6% (55/174); p < 0.001] and a
significantly shorter amniocentesis-to-delivery interval than patients without
intra-amniotic inflammation [median 35, (IQR: 10-70) versus median 71, (IQR: 47
98) days, (p < 0.0001)]. Conclusion: Sterile intra-amniotic inflammation is more
common than microbial-associated intra-amniotic inflammation in asymptomatic
women with a sonographic short cervix, and is associated with increased risk of
sPTD (<34 weeks). Further investigation is required to determine the causes of
sterile intra-amniotic inflammation and the mechanisms whereby this condition is
associated with a short cervix and sPTD.
PMID- 25123526
TI - Volume assured versus pressure preset non-invasive ventilation for compensated
ventilatory failure in COPD.
AB - BACKGROUND: The addition of domiciliary non-invasive ventilation (NIV) to
standard therapy in chronic obstructive pulmonary disease (COPD) patients with
compensated ventilatory failure (CVF) is reported to have beneficial effects.
Compliance with NIV is an important factor. Volume assured NIV (va-NIV) may
improve compliance and ventilation during sleep by automatically titrating
ventilatory pressures. METHODS: A prospective single centre, randomised, parallel
group trial comparing va-NIV and pressure preset NIV (pp-NIV) in COPD patients
with CVF naive to domiciliary NIV was performed (ISCRTN91892415). The primary
outcomes were arterial blood gases, mean overnight oximetry (mSpO2) and
compliance after three months. Secondary outcomes included pulmonary function,
exercise capacity and health-related quality of life assessment. RESULTS: Forty
patients were randomised in a 1:1 ratio. The va-NIV median target minute
ventilation was 8.4 L/min and pp-NIV median inspiratory pressure was 28 cmH2O.
There were no significant differences between groups in primary or secondary
outcomes after three months. Mean (SD) PaO2 8.7 (1.7) versus 7.9 (1.7) kPa (p =
0.19), PaCO2 6.7 (0.5) versus 7.3 (1.1) kPa (p = 0.1), mSpO2 89.7 (4.2) versus
89.8 (3.9) % (p = 0.95), compliance 5.0 (3.1) versus 4.7 (3.2) hours (p = 0.8) in
va-NIV versus pp-NIV respectively. Patients allocated va-NIV spent fewer days in
hospital initiating therapy 3.3 (1.6) versus 5.2 (2.8) (p = 0.02). Both groups
showed significant improvements in PaCO2 and mSpO2 after three months treatment.
CONCLUSIONS: Domiciliary va-NIV and pp-NIV have similar effects on physiological
outcomes in COPD patients with CVF and both are well tolerated.
PMID- 25123527
TI - Stable rates of neonatal sepsis in a tertiary neonatal unit.
AB - AIMS: To describe the rate of early- and late-onset sepsis in neonates admitted
to the neonatal intensive care unit at the Royal Women's Hospital and to compare
the rate of late-onset sepsis (LOS) with a published (2008) cohort from the same
unit. The secondary aim was to examine clinicians' compliance with antibiotic
guidelines. METHODS: Infants born <32 weeks' gestation or <1500 g admitted
between 1 July 2011 and 31 December 2011 were included. Strict definitions of
sepsis and compliance with antibiotic guidelines were applied. RESULTS: One
hundred and seventy-two infants met the inclusion criteria, with 152 having blood
culture evaluations for early-onset sepsis (EOS) and 58 having 109 evaluations
for LOS. Definite EOS occurred in 1.3% with Escherichia coli isolated. The rate
of definite LOS in 2011 of 22% was not significantly different than the 27% in
2008, with coagulase-negative staphylococcus the main isolate. Antibiotic
continuation beyond 72 h in infants with negative blood cultures was the main
reason for non-compliance with antibiotic guidelines. CONCLUSIONS: The rate of
EOS is comparable with published reports and the rate of LOS has remained stable
over a 3-year period. Discontinuation of antibiotics with negative septic markers
and blood cultures at 48-72 h is encouraged.
PMID- 25123528
TI - Synthesis and biological evaluation of new BSH-conjugated chlorin derivatives as
agents for both photodynamic therapy and boron neutron capture therapy of cancer.
AB - New disodium mercaptoundecahydro-closo-dodecaborate (BSH)-conjugated chlorin
derivatives 11, 12, 16 and 20 as agents for both photodynamic therapy (PDT) and
boron neutron capture therapy (BNCT) of cancer were synthesized. The in vivo
biodistribution and clearance of 11, 12, 16 and 20 were investigated in tumor
bearing mice. Compounds 12 and 16 showed good tumor-selective accumulation among
the four derivatives. The time to maximum accumulation of compound 16 in tumor
tissue was one-fourth of that of compound 12, and clearance from normal tissues
of compound 16 was similar to that of compound 12. The in vivo therapeutic
efficacy of PDT using 16, which has twice as many boron atoms as 12, was
evaluated by measuring tumor growth rates in tumor-bearing mice with 660 nm light
emitting diode irradiation at 6h after injection of 16. Tumor growth was
significantly inhibited by PDT using 16. These results suggested that 16 is a
good candidate for both PDT and BNCT of cancer.
PMID- 25123529
TI - Neuroblastoma in a Patient With Spinal Muscular Atrophy Type I: Is It Just a
Coincidence?
AB - Spinal muscular atrophy is an autosomal recessive disorder characterized by
progressive degeneration of anterior horn cells of the spinal cord resulting in
hypotonia, skeletal muscle atrophy, and weakness. Herein, we report a 4-month-old
male infant who presented to our hospital with an abdominal mass that was
diagnosed as neuroblastoma and spinal muscular atrophy type I. We would like to
discuss the course and differential diagnosis with an algorithm leading to the
diagnosis in this peculiar patient. To our knowledge, coexistence of spinal
muscular atrophy type I and neuroblastoma is defined for the first time in the
literature.
PMID- 25123530
TI - Large Artery Stroke in a Child With Hypoparathyroidism.
AB - The association of hypoparathyroidism and ischemic stroke is rare in childhood.
We report an interesting case of an 11-year-old girl diagnosed to have
hypoparathyroidism and presented with an acute-onset right hemiparesis.
Investigations revealed large artery ischemic stroke and uncontrolled
hypoparathyroidism. Pediatricians and pediatric neurologists should be aware of
this association in view of its potential preventive nature.
PMID- 25123531
TI - The Epidemiology of Traumatic Brain Injury in Children and Youths: A Review of
Research Since 1990.
AB - This report reviews recent research on the epidemiology of traumatic brain
injuries among children and youth aged 0 to 20 years. Studies representing
populations in North America, Europe, Australia, and New Zealand yield these
median estimates of the annual incidence of childhood brain injuries: 691 per 100
000 population treated in emergency departments, 74 per 100 000 treated in
hospital, and 9 per 100 000 resulting in death. Males have a higher risk of
injury than females: 1.4 times higher among those aged less than 10 years and 2.2
times among those older than 10 years. The leading cause of injury among children
aged less than 5 years is falls, whereas the leading cause of injury among youths
aged 15 years and older is motor vehicle crashes. The prevalence of disability
among all persons who have sustained traumatic brain injury in childhood is
unknown, but among those who were hospitalized could approximate 20%.
PMID- 25123532
TI - Microtubule-associated protein/microtubule affinity-regulating kinase 4 (MARK4)
plays a role in cell cycle progression and cytoskeletal dynamics.
AB - MARK4 is a serine-threonine kinase that phosphorylates MAP proteins, increasing
microtubule dynamics. MARK4 differs from the other members of the MARK family for
encoding two isoforms (MARK4L and MARK4S), differentially expressed in the
nervous system, and for the peculiar localisation at the centrosome and the
midbody. By cytofluorimetric analysis we showed that MARK4 is expressed
throughout the cell cycle and preferentially activated during mitosis. Depletion
of MARK4S affected the morphology and proliferation of fibroblasts and glioma
cells, as the percentages of cells in S and G2/M phases were reduced and the
percentage of cells in G1 was increased. In MARK4S silenced cells, centrosomes
were duplicated and positioned apically to the nucleus, indicating that the
centrosome cycle was altered and the cells arrested in G1 phase. Overexpression
of MARK4L or MARK4S reduced the density of the microtubule network, confirming
microtubules as the main target of MARK4, and revealed a novel co-localisation of
MARK4 and vimentin. Taken together, our data confirm that MARK4 is a key
component in the regulation of microtubule dynamics and highlight its major role
in cell cycle progression, particularly at the G1/S transition. The co
localisation of vimentin and MARK4L suggests that MARK4 has a wide-ranging
influence on cytoskeleton.
PMID- 25123534
TI - Post mortem concentrations of endogenous gamma hydroxybutyric acid (GHB) and in
vitro formation in stored blood and urine samples.
AB - Gamma-hydroxybutyrate (GHB) is a central nervous system depressant, primarily
used as a recreational drug of abuse with numerous names. It has also been
involved in various instances of drug-facilitated sexual assault due to its
potential incapacitating effects. The first aim of this paper is to measure the
post-mortem concentration of endogenous GHB in whole blood and urine samples of
30 GHB free-users, who have been divided according to the post-mortem interval
(PMI) in three groups (first group: 24-36h; second group: 37-72h; third group: 73
192h), trying to evaluate the role of PMI in affecting post mortem levels.
Second, the Authors have evaluated the new formation of GHB in vitro in blood and
urine samples of the three groups, which have been stored at -20 degrees C, 4
degrees C and 20 degrees C over a period of one month. The concentrations were
measured by GC-MS after liquid-liquid extraction according to the method
validated and published by Elliot (For. Sci. Int., 2003). For urine samples, GHB
concentrations were creatinine-normalized. In the first group the GHB mean
concentration measured after autopsy was: 2.14mg/L (range 0.54-3.21mg/L) in blood
and 3.90mg/g (range 0.60-4.81mg/g) in urine; in the second group it was: 5.13mg/L
(range 1.11-9.60mg/L) in blood and 3.93mg/g (range 0.91-7.25mg/g) in urine; in
the third group it was: 11.8mg/L (range 3.95-24.12mg/L) in blood and 9.83mg/g
(range 3.67-21.90mg/g) in urine. The results obtained in blood and urine samples
showed a statistically significant difference among groups (p<0.001) in the first
analysis performed immediately after autopsy. Throughout the period of
investigation up to 4 weeks, the comparison of storage temperatures within each
group showed in blood and urine samples a mean difference at 20 degrees C
compared to -20 degrees C not statistically significant at the 10% level. These
findings allow us to affirm that the PMI strongly affects the post mortem
production of GHB in blood and urine samples. Regarding the new formation of GHB
in vitro both in blood and urine samples of the three groups, which have been
stored at -20 degrees C, 4 degrees C and 20 degrees C over a period of one month,
although there was no significant increases of GHB levels throughout the period
of investigation, the lowest increases were found both in blood and urine at -20
degrees C, therefore we recommend the latter as optimal storage temperature.
PMID- 25123533
TI - A quantitative multiplexed mass spectrometry assay for studying the kinetic of
residue-specific histone acetylation.
AB - Histone acetylation is involved in gene regulation and, most importantly,
aberrant regulation of histone acetylation is correlated with major human
diseases. Although many lysine acetyltransferases (KATs) have been characterized
as being capable of acetylating multiple lysine residues on histones, how
different factors such as enzyme complexes or external stimuli (e.g. KAT
activators or inhibitors) alter KAT specificity remains elusive. In order to
comprehensively understand how the homeostasis of histone acetylation is
maintained, a method that can quantitate acetylation levels of individual lysines
on histones is needed. Here we demonstrate that our mass spectrometry (MS)-based
method accomplishes this goal. In addition, the high throughput, high
sensitivity, and high dynamic range of this method allows for effectively and
accurately studying steady-state kinetics. Based on the kinetic parameters from
in vitro enzymatic assays, we can determine the specificity and selectivity of a
KAT and use this information to understand what factors influence histone
acetylation. These approaches can be used to study the enzymatic mechanisms of
histone acetylation as well as be adapted to other histone modifications.
Understanding the post-translational modification of individual residues within
the histones will provide a better picture of chromatin regulation in the cell.
PMID- 25123535
TI - Arsenic trioxide prevents rat pulmonary fibrosis via miR-98 overexpression.
AB - AIMS: This study aimed to investigate the pathogenesis mechanisms of bleomycin
(BLM)-induced pulmonary fibrosis (PF) in Sprague-Dawley rats and explore the anti
fibrotic role of arsenic trioxide (As2O3) in preventing PF. MAIN METHODS:
Intratracheal instillation of BLM was performed to establish PF rat models. The
treatment group was treated with As2O3 (0.4 mg/kg/day). Morphological changes
were observed by hematoxylin-eosin and Masson staining. Related proteins were
determined by immunohistochemistry, immunofluorescence, and Western blot.
MicroRNA detection was performed by quantitative real-time polymerase chain
reaction. KEY FINDINGS: As a novel miRNA in PF, miR-98 decreased in the fibrotic
lung tissues. Based on microRNA analysis software, we found that Stat3-3'-UTR is
targeted by miR-98. Then, we found that Stat3 was activated with PF development
and the expression of Stat3 and p-Stat3 was significantly increased in BLM
induced PF at day 28 compared with saline-treated rats. Our results showed that
both Stat3 and p-Stat3 were significantly decreased in miR-98-treated A549 cells
compared with that in mu-98-treated cultures or untreated controls. The fibrotic
marker alpha-SMA was upregulated, whereas E-cadherin was inhibited in fibrotic
lung tissues. The ratio of apoptotic factors Bax/Bcl-2 increased with the
development of fibrosis. Furthermore, As2O3 treatment prevented lung interstitial
thickening and inhibited the collagen type I and hydroxyproline, thereby
preventing the development of PF. As2O3 also significantly down-regulated alpha
SMA but increased E-cadherin and miR-98 levels. SIGNIFICANCE: The study revealed
that arsenic trioxide prevented rat PF by up-regulation of miR-98 and inhibition
of its downstream Stat3 signals.
PMID- 25123536
TI - Insulin acutely triggers transcription of Slc2a4 gene: participation of the AT
rich, E-box and NFKB-binding sites.
AB - AIMS: The insulin-sensitive glucose transporter protein GLUT4 (solute carrier
family 2 member 4 (Slc2a4) gene) plays a key role in glycemic homeostasis.
Decreased GLUT4 expression is a current feature in insulin resistant conditions
such as diabetes, and the restoration of GLUT4 content improves glycemic control.
This study investigated the effect of insulin upon Slc2a4/GLUT4 expression,
focusing on the AT-rich element, E-box and nuclear factor NF-kappa-B (NFKB) site.
MAIN METHODS: Rat soleus muscles were incubated during 180 min with insulin,
added or not with wortmannin (phosphatidylinositol-4,5-bisphosphate 3-kinase
catalytic subunit gamma isoform (PI3K)-inhibitor), ML9 (serine/threonine protein
kinase (AKT) inhibitor) and tumor necrosis factor (TNF, GLUT4 repressor), and
processed for analysis of GLUT4 protein (Western blotting); Slc2a4, myocyte
enhancer factor 2a/d (Mef2a/d), hypoxia inducible factor 1a (Hif1a), myogenic
differentiation 1 (Myod1) and nuclear factor of kappa light polypeptide gene
enhancer in B-cells 1 (Nfkb1) messenger ribonucleic acids (mRNAs) (polymerase
chain reaction (PCR)); and AT-rich- (myocyte-specific enhancer factor 2 (MEF2)
binding site), E-box- (hypoxia inducible factor 1 alpha (HIF1A)- and myoblast
determination protein 1 (MYOD1)-binding site), and NFKB-binding activity
(electrophoretic mobility assay). KEY FINDINGS: Insulin increased Slc2a4 mRNA
expression (140%) and nuclear proteins binding to AT-rich and E-box elements
(~90%), all effects were prevented by wortmannin and ML9. Insulin also increased
Mef2a/d and Myod1 mRNA expression, suggesting the participation of these
transcriptional factors in the Slc2a4 enhancing effect. Conversely, insulin
decreased Nfkb1 mRNA expression and protein binding to the NFKB-site (~50%).
Furthermore, TNF-induced inhibition of GLUT4 expression (~40%) was prevented by
insulin in an NFKB-binding repressing mechanism. GLUT4 protein paralleled the
Slc2a4 mRNA regulations. SIGNIFICANCE: Insulin enhances the Slc2a4/GLUT4
expression in the skeletal muscle by activating AT-rich and E-box elements, in a
PI3K/AKT-dependent mechanism, and repressing NFKB-site activity as well. These
results unravel how post-prandial increase of insulin may guarantee GLUT4
expression, and how the insulin signaling impairment can participate in insulin
resistance-induced repression of GLUT4.
PMID- 25123538
TI - Efficient heteronuclear decoupling in MAS solid-state NMR using non-rotor
synchronized rCW irradiation.
AB - We present new non-rotor-synchronized variants of the recently introduced
refocused continuous wave (rCW) heteronuclear decoupling method significantly
improving the performance relative to the original rotor-synchronized variants.
Under non-rotor-synchronized conditions the rCW decoupling sequences provide more
efficient decoupling, are easier to setup, and prove more robust towards
experimental parameters such as radio frequency (rf) field amplitude and spinning
frequency. This is demonstrated through numerical simulations substantiated with
experimental results under different sample spinning and rf field amplitude
conditions for powder samples of U-(13)C-glycine and U-(13)C-L-histidine.HCl.H2O.
PMID- 25123537
TI - Leptin-mediated inflammatory signaling crucially links visceral fat inflammation
to obesity-associated beta-cell dysfunction.
AB - AIM: This study aimed to examine the causal relationship between adipokines
released from visceral fat and pancreatic beta-cell dysfunction in the state of
obesity inflammation. MAIN METHODS: Adipose tissue and adipocyte conditioned
medium were obtained from epididymal fat of B6 mice on regular or high fat diet
for 16 weeks. The latter were classified into two groups: overweight (OW, 40+/
2g) and obese (OB, 50+/-2g). Isolated mouse islets and NIT-1 cells were used to
evaluate beta-cell function. KEY FINDINGS: Fasting glucose, leptin, and
interleukin-6 levels were increased in OW mice and were further elevated in OB
mice. Adipocyte size and number of adipose macrophage infiltrations showed a
similar trend. The augmentation of homeostasis model assessment of insulin
resistance, islet hyperplasia and macrophage infiltration was noted only in OB
mice. The stimulation index was lower, but reactive oxygen species production was
higher in islets isolated from OB mice than from controls. In epididymal fat
conditioned medium, the increases in leptin, IL-6 and TNF-alpha production in OW
mice were further elevated in OB mice except TNF-alpha. Adipose tissue
conditioned medium suppressed the stimulation index of islets isolated from B6
mice but not from db/db mice. The suppressive effect was also reversed by co
treatment with N-acetylcysteine or NS-398 (a selective cyclooxygenase-2
inhibitor). SIGNIFICANCE: A markedly elevated leptin production from inflamed
visceral fat could deteriorate beta-cell function via leptin receptor-mediated
oxidative stress and cyclooxygenase-2 activation in the development of obesity.
PMID- 25123539
TI - Determining pore length scales and pore surface relaxivity of rock cores by
internal magnetic fields modulation at 2MHz NMR.
AB - Pore length scales and pore surface relaxivities of rock cores with different
lithologies were studied on a 2MHz Rock Core Analyzer. To determine the pore
length scales of the rock cores, the high eigenmodes of spin bearing molecules
satisfying the diffusion equation were detected with optimized encoding periods
in the presence of internal magnetic fields Bin. The results were confirmed using
a 64MHz NMR system, which supports the feasibility of high eigenmode detection at
fields as low as 2MHz. Furthermore, this methodology was combined with
relaxometry measurements to a two-dimensional experiment, which provides
correlation between pore length and relaxation time. This techniques also yields
information on the surface relaxivity of the rock cores. The estimated surface
relaxivities were then compared to the results using an independent NMR method.
PMID- 25123540
TI - Achieving 1% NMR polarization in water in less than 1min using SABRE.
AB - The development of biocompatible hyperpolarized media is a crucial step towards
application of hyperpolarization in vivo. This article describes the achievement
of 1% hyperpolarization of 3-amino-1,2,4-triazine protons in water using the
parahydrogen induced polarization technique based on signal amplification by
reversible exchange (SABRE). Polarization was achieved in less than 1 min.
PMID- 25123541
TI - A 3D experiment that provides isotropic homonuclear correlations of half-integer
quadrupolar nuclei.
AB - Two 3D experiments, capable of producing enhanced resolution two-spin double
quantum (DQ) homonuclear correlations for half-integer quadrupolar nuclei, are
described. The first uses a split-t1 MQMAS sequence followed by a sandwiched
oR(3) symmetry-based dipolar recoupling sequence to directly excite DQ
coherences. In this case an isotropic single-quantum (SQ) coherence starts the
homonuclear DQ excitation. In the second experiment a single strong pulse is used
to create triple quantum (TQ) coherence followed by a further single pulse
conversion to zero-order before a non-sandwiched oR(3) DQ sequence. The first
experiment is demonstrated using (87)Rb in RbNO3, with three Rb sites in a ~5ppm
range, and the second to (11)B in caesium triborate, CsB3O5, with two three
coordinated sites separated by ~2ppm and one four-coordinated boron site. In both
cases, all sites are clearly resolved and their connections observed. The second
experiment has higher sensitivity and a good signal to noise is obtained in a
reasonable time despite the long T1 relaxation time of (11)B in this material.
PMID- 25123542
TI - The interaction of a cobalt porphyrin with cancer-associated nitrosamines.
AB - A cobalt porphyrin (CY-B) was presented, and its interaction with tobacco
specific nitrosamines (TSNAs) was investigated by UV-Vis spectroscopy and high
resolution mass spectrometry. The results revealed that the stoichiometry of the
host-guest interaction was 1:2 and that the binding constant between CY-B and
TSNAs was within the range of 0.78*10(8)-7.83*10(8)M(-2). The coordination
strength between CY-B and TSNAs decreased in the sequence of NNN>NAB>NAT>NNK
based on the binding constant. The interaction mechanism of CY-B with TSNAs
involved a coordination interaction, and the pi-pi interaction between the
porphyrin macrocycle and the aromatic frame of the TSNAs pyridines may also have
been a driving force. The measured thermodynamic properties demonstrated that the
reaction of CY-B with TSNAs was spontaneous and that the driving force for the
interaction was a change in enthalpy. The reaction was exothermic, and an
increasing temperature inhibited the interaction. The IR spectrum of the complex
revealed that the NNO group of TSNAs and the metal cobalt of CY-B formed the six
coordinate complex.
PMID- 25123544
TI - Identifying the contents of a type 1 diabetes outpatient care program based on
the self-adjustment of insulin using the Delphi method.
AB - AIM: The objective of this study is to identify the items necessary for an
outpatient care program based on the self-adjustment of insulin for type 1
diabetes patients. METHODS: Two surveys based on the Delphi method were
conducted. The survey participants were 41 certified diabetes nurses in Japan. An
outpatient care program based on the self-adjustment of insulin was developed
based on pertinent published work and expert opinions. RESULTS: There were a
total of 87 survey items in the questionnaire, which was developed based on the
care program mentioned earlier, covering matters such as the establishment of
prerequisites and a cooperative relationship, the basics of blood glucose pattern
management, learning and practice sessions for the self-adjustment of insulin,
the implementation of the self-adjustment of insulin, and feedback. The
participants' approval on items in the questionnaires was defined at 70%.
Participants agreed on all of the items in the first survey. Four new parameters
were added to make a total of 91 items for the second survey and participants
agreed on the inclusion of 84 of them. CONCLUSION: Items necessary for a type 1
diabetes outpatient care program based on self-adjustment of insulin were
subsequently selected. It is believed that this care program received a fairly
strong approval from certified diabetes nurses; however, it will be necessary to
have the program further evaluated in conjunction with intervention studies in
the future.
PMID- 25123543
TI - Adverse event reporting in nonpharmacologic, noninterventional pain clinical
trials: ACTTION systematic review.
AB - Assessment of treatment safety is 1 of the primary goals of clinical trials.
Organizations and working groups have created reporting guidelines for adverse
events (AEs). Previous research examining AE reporting for pharmacologic clinical
trials of analgesics in major pain journals found many reporting inadequacies,
suggesting that analgesic trials are not adhering to existing AE reporting
guidelines. The present systematic review documented AE reporting in 3 main pain
journals for nonpharmacologic, noninterventional (NP/NI) trials examining pain
treatments. To broaden our pool of nonpharmacologic trials, we also included
trials examining acupuncture, leech therapy, and noninvasive stimulation
techniques (eg, transcutaneous electrical nerve stimulation). We documented AE
reporting at 2 levels of specificity using coding manuals based on the
Consolidated Standards of Reporting Trials (CONSORT) harms reporting standards
and Analgesic, Anesthetic, and Addiction Clinical Trial Translations,
Innovations, Opportunities, and Networks (ACTTION) AE reporting checklist. We
identified a number of inadequacies in AE reporting across the 3 journals. For
example, using the ACTTION coding manual, we found that less than one-half of the
trials reported specific AE assessment methods; approximately one-third of the
trials reported withdrawals due to AEs for each study arm; and about one-fourth
of the trials reported all specific AEs. We also examined differences in AE
reporting across several trial characteristics, finding that AE reporting was
generally more detailed in trials with patients versus those using healthy
volunteers undergoing experimentally evoked pain. These results suggest that
investigators conducting and reporting NP/NI clinical trials are not adequately
describing the assessment and occurrence of AEs.
PMID- 25123545
TI - A pleomorphic carcinoma of the lung producing multiple cytokines and forming a
rapidly progressive mass-like opacity.
AB - BACKGROUND: Lung cancer cells have been reported to produce cytokines, resulting
in systemic reactions. There have been few reports showing that these cytokines
induced the formation of an inflammatory mass around lung cancers. CASE
PRESENTATION: We encountered a patient with a pleomorphic carcinoma of the lung.
This tumor produced interleukin (IL)-8, granulocyte colony-stimulating factor and
IL-6, which in turn recruited inflammatory cells, such as CD8 positive
lymphocytes, around the tumor, resulting in a rapidly growing tumor shadow.
CONCLUSION: 18 F-fluoro-deoxy-glucose positron emission tomography, in addition
to a conventional radiological approach such as computed tomography, may detect
immunological responses around a tumor.
PMID- 25123546
TI - Demographic history and gene flow during silkworm domestication.
AB - BACKGROUND: Gene flow plays an important role in domestication history of
domesticated species. However, little is known about the demographic history of
domesticated silkworm involving gene flow with its wild relative. RESULTS: In
this study, four model-based evolutionary scenarios to describe the demographic
history of B. mori were hypothesized. Using Approximate Bayesian Computation
method and DNA sequence data from 29 nuclear loci, we found that the gene flow at
bottleneck model is the most likely scenario for silkworm domestication. The
starting time of silkworm domestication was estimated to be approximate 7,500
years ago; the time of domestication termination was 3,984 years ago. Using
coalescent simulation analysis, we also found that bi-directional gene flow
occurred during silkworm domestication. CONCLUSIONS: Estimates of silkworm
domestication time are nearly consistent with the archeological evidence and our
previous results. Importantly, we found that the bi-directional gene flow might
occur during silkworm domestication. Our findings add a dimension to highlight
the important role of gene flow in domestication of crops and animals.
PMID- 25123547
TI - Camello, a novel family of Histone Acetyltransferases that acetylate histone H4
and is essential for zebrafish development.
AB - In this study, we have investigated genome-wide occurrence of Histone
Acetyltransferases (HATs) in genomes of Mus musculus and Danio rerio on the basis
of presence of HAT domain. Our study identified a group of proteins that lacks
characteristic features of known HAT families, relatively smaller in size and has
no other associated domains. Most of the proteins in this unclassified group are
Camello proteins, which are not yet known and classified as functional HATs. Our
in vitro and in vivo analysis revealed that Camello family proteins are active
HATs and exhibit specificity towards histone H4. Interestingly, Camello proteins
are among the first identified HATs showing perinuclear localization. Moreover,
Camello proteins are evolutionarily conserved in all chordates and are observed
for the first time in cnidarians in phylogeny. Furthermore, knockdown of Camello
protein (CMLO3) in zebrafish embryos exhibited defects in axis elongation and
head formation. Thus, our study identified a novel family of active HATs that is
specific for histone H4 acetylation, exhibits perinuclear localization and is
essential for zebrafish development.
PMID- 25123548
TI - Relating working memory to compression parameters in clinically fit hearing AIDS.
AB - PURPOSE: Several laboratory studies have demonstrated that working memory may
influence response to compression speed in controlled (i.e., laboratory)
comparisons of compression. In this study, the authors explored whether the same
relationship would occur under less controlled conditions, as might occur in a
typical audiology clinic. METHOD: Participants included 27 older adults who
sought hearing care in a private practice audiology clinic. Working memory was
measured for each participant using a reading span test. The authors examined the
relationship between working memory and aided speech recognition in noise, using
clinically fit hearing aids with a range of compression speeds. RESULTS: Working
memory, amount of hearing loss, and age each contributed to speech recognition,
but the contribution depended on the speed of the compression processor. For fast
acting compression, the best performance was obtained by patients with high
working memory. For slow-acting compression, speech recognition was affected by
age and amount of hearing loss but was not affected by working memory.
CONCLUSIONS: Despite the expectation of greater variability from differences in
compression implementation, number of compression channels, or attendant signal
processing, the relationship between working memory and compression speed showed
a similar pattern as results from more controlled, laboratory-based studies.
PMID- 25123550
TI - GRAIDs: a framework for closing the gap in the availability of health promotion
programs and interventions for people with disabilities.
AB - BACKGROUND: Evidence-based health promotion programs developed and tested in the
general population typically exclude people with disabilities. To address this
gap, a set of methods and criteria were created to adapt evidence-based health
promotion programs for people with disabilities. In this first study, we describe
a framework for adapting evidence-based obesity prevention strategies for people
with disabilities. We illustrate how the framework has been used to adapt the
U.S. Centers for Disease Control and Prevention's (CDC) obesity prevention
strategies for individuals with physical and developmental disabilities. METHODS:
The development of inclusion guidelines, recommendations and adaptations for
obesity prevention (referred to as GRAIDs--Guidelines, Recommendations,
Adaptations Including Disability) consists of five components: (i) a scoping
review of the published and grey literature; (ii) an expert workgroup composed of
nationally recognized leaders in disability and health promotion who review,
discuss and modify the scoping review materials and develop the content into
draft GRAIDs; (iii) focus groups with individuals with disabilities and their
family members (conducted separately) who provide input on the potential
applicability of the proposed GRAIDs in real world settings; (iv) a national
consensus meeting with 21 expert panel members who review and vote on a final set
of GRAIDs; and (v) an independent peer review of GRAIDs by national leaders from
key disability organizations and professional groups through an online web
portal. RESULTS: This is an ongoing project, and to date, the process has been
used to develop 11 GRAIDs to coincide with 11 of the 24 CDC obesity prevention
strategies. CONCLUSION: A set of methods and criteria have been developed to
allow researchers, practitioners and government agencies to promote inclusive
health promotion guidelines, strategies and practices for people with
disabilities. Evidence-based programs developed for people without disabilities
can now be adapted for people with disabilities using the GRAIDs framework.
PMID- 25123549
TI - Younger age, higher body mass index and lower adiponectin concentration predict
higher serum thromboxane B2 level in aspirin-treated patients with type 2
diabetes: an observational study.
AB - BACKGROUND: Evidence from the literature suggests diminished acetylsalicylic acid
(ASA) treatment efficacy in type 2 diabetes (DM2). High on-aspirin platelet
reactivity (HAPR) in DM2 has been linked to poor glycemic and lipid control.
However, there are no consistent data on the association between HAPR and insulin
resistance or adipose tissue metabolic activity. The aim of this study was to
assess the relationship between laboratory response to ASA and metabolic control,
insulin resistance and adipokines in DM2. METHODS: A total of 186 DM2 patients
treated with oral antidiabetic drugs and receiving 75 mg ASA daily were included
in the analysis. Response to ASA was assessed by measuring serum thromboxane B2
(TXB2) concentration and expressed as quartiles of TXB2 level. The achievement of
treatment targets in terms of glycemic and lipid control, insulin resistance
parameters (including Homeostatic Model Assessment-Insulin Resistance, HOMA-IR,
index), and serum concentrations of high-molecular weight (HMW) adiponectin,
leptin and resistin, were evaluated in all patients. Univariate and multivariate
logistic regression analyses were performed to determine the predictive factors
of serum TXB2 concentration above the upper quartile and above the median.
RESULTS: Significant trends in age, body mass index (BMI), HOMA-IR, HMW
adiponectin concentration, C-reactive protein concentration and the frequency of
achieving target triglyceride levels were observed across increasing quartiles of
TXB2. In a multivariate analysis, only younger age and higher BMI were
independent predictors of TXB2 concentration above the upper quartile, while
younger age and lower HMW adiponectin concentration were predictors of TXB2
concentration above the median. CONCLUSIONS: These results suggest that in DM2,
the most important predictor of HAPR is younger age. Younger DM2 patients may
therefore require total daily ASA doses higher than 75 mg, preferably as a twice
daily regimen, to achieve full therapeutic effect. Higher BMI and lower HMW
adiponectin concentration were also associated with less potent ASA effect. This
is the first study to demonstrate an association of lower adiponectin
concentration with higher serum TXB2 level in patients treated with ASA.
PMID- 25123551
TI - Sweet taste sensitivity in pre-diabetics, diabetics and normoglycemic controls: a
comparative cross sectional study.
AB - BACKGROUND: Increasing prevalence of pre-diabetes is an emerging public health
problem. Decrease in sweet taste sensitivity which can lead to an increase in
sugar intake might be a factor driving them to overt diabetes. The aim of the
present study was to assess the sweet taste sensitivity in pre-diabetics in
comparison with diabetics and with normoglycemic controls. METHODS: Forty pre
diabetics, 40 diabetics and 34 normoglycemic controls were studied. The three
groups were matched for age, sex and BMI. The division into groups was based on
their glycated hemoglobin levels. The detection and recognition thresholds were
determined by the multiple forced-choice method using sucrose solutions prepared
in 1/4 log dilutions. The intensities of perceived sensations for a series of
suprathreshold concentrations of sucrose solutions prepared in 1/2 log dilution
were determined by rating on a visual analogue scale. Statistical analyses were
performed by SPSS version 21. RESULTS: The mean (SD) detection thresholds of
diabetic, pre-diabetic and normoglycemic groups were 0.025 (0.01), 0.018 (0.01)
and 0.015 (0.01) respectively with a significant increase in diabetic group
compared to normoglycemic group (p = 0.03). The mean recognition thresholds were
not different among the three groups. When the intensity ratings for
suprathreshold concentrations of sucrose were compared between the three groups,
for all suprathreshold concentrations tested, significant differences were
observed across the four concentrations (p < 0.001) and between groups in
suprathreshold ratings (p < 0.05). Further analysis showed that the diabetic
group had significantly lower suprathreshold ratings than the normoglycemic group
(p < 0.001). Although all mean suprathreshold intensity ratings of the pre
diabetic group were between the normoglycemic and diabetic groups, the
differences were not significant. CONCLUSIONS: This is the first study to
demonstrate the sweet taste sensitivity in pre-diabetics. The findings of the
present study do not support the hypothesis of decreased sweet taste sensitivity
of pre-diabetics. However, the results confirm the previous findings of blunted
taste response in diabetics. The observation of pre-diabetics having intermediate
values for all taste thresholds and suprathreshold ratings warrants a future
investigation with a larger pre-diabetic sample recruited with more specific
screening criteria to test this hypothesis further.
PMID- 25123552
TI - Population model of longitudinal FEV1 data in asthmatics: meta-analysis and
predictability of placebo response.
AB - Asthma is an obstructive lung disease where the mechanism of disease progression
is not fully understood hence motivating the use of empirical models to describe
the evolution of the patient's health state. With reference to placebo response,
measured in terms of FEV1 (Forced Expiratory Volume in 1 s), a range of empirical
models taken from the literature were compared at a single trial level. In
particular, eleven GSK trials lasting 12 weeks in mild-to-moderate asthma were
used for the modelling of longitudinal placebo responses. Then, the chosen
exponential model was used to carry out an individual participant data meta
analysis on eleven trials. A covariate analysis was also performed to find
relevant covariates in asthma to be accounted for in the meta-analysis model.
Age, gender, and height were found statistically significant (e.g. the taller the
patients the higher the FEV1, the older the patients the lower the FEV1, and
females have lower FEV1). By truncating each trial at week 4, the predictive
properties of the meta-analysis model were also investigated, showing its ability
to predict long-term FEV1 response from truncated trials. Summarizing, the study
suggests that: (i) the exponential model effectively describes the placebo
response; (ii) the meta-analysis approach may prove helpful to simulate new
trials as well as to reduce trial duration in view of its predictive properties;
(iii) the inclusion of available covariates within the meta-analysis model
provides a reduction of the inter-individual variability.
PMID- 25123553
TI - Goal setting and knowledge generation through health policy and systems research
in low- and middle-income countries.
AB - The importance of health policy and systems research (HPSR) and its role in
aiding health system reforms has been increasingly recognized in recent years
within the World Health Organization (WHO). An assessment of the 71 WHO Country
Cooperation Strategies (CCS) that are publicly available and were published in
English in 2012 was completed to determine the extent to which HPSR goals are
incorporated at the global level. A review was then conducted using a Medline
database search to determine the number of articles published by countries with
HPSR goals. Sixty-six out of the 71 (93%) available CCS describe HPSR as an
objective or strategy for achieving health system priorities. However, only 52
out of the 66 countries (79%) have any publications involving HPSR during their
most recent CCS cycle. This suggests that although health systems strengthening
through HPSR is increasingly emphasized by the WHO and country health ministries,
actual HPSR progress may still be lacking. There is a need and an opportunity for
the WHO and other global health agencies to focus on providing the necessary
tools and building HPSR capacity in low- and middle-income countries.
PMID- 25123554
TI - Positive and negative affective states and disease activity in ankylosing
spondylitis.
AB - The aim of the study was to explore the influence of psychological affective
states such as cheerfulness and bad mood on self-reported disease activity in
patients with ankylosing spondylitis (AS) while controlling for demographic and
clinical variables. Patients attending a biological therapy unit were selected
for a cross-sectional study if they met the criteria for AS and were already
receiving treatment. Their psychological affective state was assessed with the
state version of the State-Trait Cheerfulness Inventory. Clinical variables
included were patient-reported disease activity using the Bath Ankylosing
Spondylitis Disease Activity Index (BASDAI) and acute-phase reactants. We
performed univariate and multivariate analyses to verify the robustness of the
relationship between psychological affective states and disease activity. We also
explored whether disease activity, measured either by self-report or by acute
phase reactants, was influenced by patient's overall affective state. In the
recruited 31 patients with AS, overall affective state contributed significantly
to the variance in BASDAI scores, adding 21.8% to the overall R-square of the
predictive power of clinical and demographic variables (combined R-square = 17%).
A higher positive affective state was associated with lower values of C-reactive
protein (p < 0.05). Results of a bootstrapping procedure showed that the
relationship between C-reactive protein levels and BASDAI scores was mediated by
overall affective state. In patients with AS, affective state can induce
variability in self-reported disease activity. Patients' overall affective state
can explain the relationship between acute-phase reactants and self-reported
scores. These findings suggest interesting possibilities for the monitoring of
disease activity in AS.
PMID- 25123555
TI - Toxicity of nanomaterials; an undermined issue.
AB - Nanomaterials are employed in extensive variety of commercial products such as
electronic components, cosmetics, food, sports equipment, biomedical
applications, and medicine. With the increasing utilization of engineered
nanomaterials, the potential exposure of human to nanoparticles is rapidly
increasing. Nowadays when new nanomaterials with new applications are introduced,
mostly good and positive effects are mentioned whereas possible hazards arising
from nanosize of the compounds are undermined. Toxicology studies of
nanomaterials demonstrate some adverse effects in some human organs such as
central nerve system, immune system, and lung. There is lack of complete
information about human toxicity and environmental waste of nanomaterials. We
aimed to highlight current toxicological concerns of potentially useful
nanomaterials which are now used in pharmaceutical and biomedical sciences.
PMID- 25123557
TI - Bioreactor study employing bacteria with enhanced activity toward cyanobacterial
toxins microcystins.
AB - An important aim of white (grey) biotechnology is bioremediation, where microbes
are employed to remove unwanted chemicals. Microcystins (MCs) and other
cyanobacterial toxins are not industrial or agricultural pollutants; however,
their occurrence as a consequence of human activity and water reservoir
eutrophication is regarded as anthropogenic. Microbial degradation of
microcystins is suggested as an alternative to chemical and physical methods of
their elimination. This paper describes a possible technique of the practical
application of the biodegradation process. The idea relies on the utilization of
bacteria with a significantly enhanced MC-degradation ability (in comparison with
wild strains). The cells of an Escherichia coli laboratory strain expressing
microcystinase (MlrA) responsible for the detoxification of MCs were immobilized
in alginate beads. The degradation potency of the tested bioreactors was
monitored by HPLC detection of linear microcystin LR (MC-LR) as the MlrA
degradation product. An open system based on a column filled with alginate
entrapped cells was shown to operate more efficiently than a closed system
(alginate beads shaken in a glass container). The maximal degradation rate
calculated per one liter of carrier was 219.9 ug h-1 of degraded MC-LR. A
comparison of the efficiency of the described system with other biological and
chemo-physical proposals suggests that this new idea presents several advantages
and is worth investigating in future studies.
PMID- 25123556
TI - Synthesis and analgesic effects of MU-TRTX-Hhn1b on models of inflammatory and
neuropathic pain.
AB - MU-TRTX-Hhn1b (HNTX-IV) is a 35-amino acid peptide isolated from the venom of the
spider, Ornithoctonus hainana. It inhibits voltage-gated sodium channel Nav1.7,
which has been considered as a therapeutic target for pain. The goal of the
present study is to elucidate the analgesic effects of synthetic MU-TRTX-Hhn1b on
animal models of pain. The peptide was first synthesized and then successfully
refolded/oxidized. The synthetic peptide had the same inhibitory effect on human
Nav1.7 current transiently expressed in HEK 293 cells as the native toxin.
Furthermore, the analgesic potentials of the synthetic peptide were examined on
models of inflammatory pain and neuropathic pain. MU-TRTX-Hhn1b produced an
efficient reversal of acute nociceptive pain in the abdominal constriction model,
and significantly reduced the pain scores over the 40-min period in the formalin
model. The efficiency of MU-TRTX-Hhn1b on both models was equivalent to that of
morphine. In the spinal nerve model, the reversal effect of MU-TRTX-Hhn1b on
allodynia was longer and higher than mexiletine. These results demonstrated that
MU-TRTX-Hhn1b efficiently alleviated acute inflammatory pain and chronic
neuropathic pain in animals and provided an attractive template for further
clinical analgesic drug design.
PMID- 25123559
TI - Protective antigen-specific memory B cells persist years after anthrax
vaccination and correlate with humoral immunity.
AB - Anthrax Vaccine Adsorbed (AVA) generates short-lived protective antigen (PA)
specific IgG that correlates with in vitro toxin neutralization and protection
from Bacillus anthracis challenge. Animal studies suggest that when PA-specific
IgG has waned, survival after spore challenge correlates with an activation of PA
specific memory B cells. Here, we characterize the quantity and the longevity of
AVA-induced memory B cell responses in humans. Peripheral blood mononuclear cells
(PBMCs) from individuals vaccinated >=3 times with AVA (n = 50) were collected
early (3-6 months, n = 27) or late after their last vaccination (2-5 years, n =
23), pan-stimulated, and assayed by ELISPOT for total and PA-specific memory B
cells differentiated into antibody secreting cells (ASCs). PA-specific ASC
percentages ranged from 0.02% to 6.25% (median: 1.57%) and did not differ between
early and late post-vaccination individuals. PA-specific ASC percentages
correlated with plasma PA-specific IgG (r = 0.42, p = 0.03) and toxin
neutralization (r = 0.52, p = 0.003) early post vaccination. PA-specific ASC
percentages correlated with supernatant anti-PA both early (r = 0.60, p = 0.001)
and late post vaccination (r = 0.71, p < 0.0001). These data suggest PA-specific
memory B cell responses are long-lived and can be estimated after recent
vaccination by the magnitude and neutralization capacity of the humoral response.
PMID- 25123560
TI - [Visual diagnosis while performing transurethral resection of bladder tumors:
power or myth?].
AB - INTRODUCTION: The gold standard for diagnosis and immediate therapy of bladder
cancer is a transurethral resection (TURB) followed by histopathologic
evaluation. The aim of this study was to assess the reliability of visual
diagnosis by the operating urologist concerning dignity (malignant/benign) and
staging compared to histopathologic evaluation. This is especially crucial since
early mitomycin C instillation is based on the urologist's first impression.
STUDY DESIGN AND METHODS: This prospective study included 311 cases of TURB from
five German institutions. Surgeons were asked to estimate dignity of the
neoplasm, tumor stage, and grade according to a standardized questionnaire.
RESULTS: The subjective estimation/visual diagnosis of the operating urologist
achieved a sensitivity with respect to identifying malignant tumors as such of
97%, while specificity was only 41%. Accordingly, the positive (PPV) and negative
predictive values (NPV) were 76% and 88%, respectively. In general, muscle
invasive cancer was predicted more often than confirmed by pathology (PPV 52%).
However, whenever muscle invasive cancer was excluded by the urologist, this was
confirmed by the pathologist in most the cases (NPV 95%). The educational degree
did not influence the reliability and predictive value of visual diagnosis.
CONCLUSION: This study shows that urologists cannot reliably distinguish benign
from malignant lesions of bladder mucosa-regardless of their educational degree.
A reliable diagnosis of a pathologist is definitely needed to plan final
therapeutic steps.
PMID- 25123558
TI - Molecular approaches to improve the insecticidal activity of Bacillus
thuringiensis Cry toxins.
AB - Bacillus thuringiensis (Bt) is a gram-positive spore-forming soil bacterium that
is distributed worldwide. Originally recognized as a pathogen of the silkworm,
several strains were found on epizootic events in insect pests. In the 1960s, Bt
began to be successfully used to control insect pests in agriculture,
particularly because of its specificity, which reflects directly on their lack of
cytotoxicity to human health, non-target organisms and the environment. Since the
introduction of transgenic plants expressing Bt genes in the mid-1980s, numerous
methodologies have been used to search for and improve toxins derived from native
Bt strains. These improvements directly influence the increase in productivity
and the decreased use of chemical insecticides on Bt-crops. Recently, DNA
shuffling and in silico evaluations are emerging as promising tools for the
development and exploration of mutant Bt toxins with enhanced activity against
target insect pests. In this report, we describe natural and in vitro evolution
of Cry toxins, as well as their relevance in the mechanism of action for insect
control. Moreover, the use of DNA shuffling to improve two Bt toxins will be
discussed together with in silico analyses of the generated mutations to evaluate
their potential effect on protein structure and cytotoxicity.
PMID- 25123561
TI - [Influence of ureter stenting before ureterorenoscopic treatment of ureteral
calculi].
AB - BACKGROUND: Due to a worldwide rise of incidence, urolithiasis presents an
increasing strain on the health system. Ureterorenoscopy (URS) is a standard
treatment to extract stones in case of ureteral calculi. To increase the success
rate of URS and to minimize complications, preoperative ureteral stenting
(prestenting) has previously been described as suitable. However, published data
are still conflicting. This article describes our single-center experience on the
influence of prestenting on the outcome of ureterorenoscopic stone therapy.
METHODS: A total of 442 patients who had undergone ureterorenoscopic stone
extraction at the Wolfsburg Clinic between 2010 and 2011 were retrospectively
evaluated regarding peri- and postoperative results. The Fisher's exact, the
chi(2), and the Mann-Whitney U test were used to compare the group of patients
with and without prestenting. RESULTS: Even though patients with prestenting
suffered from stones with larger diameter that were more frequently located in
the proximal ureter, the rates for postoperative stenting, perioperative
complications, and retreatment were much lower then in the group of patients
without prestenting (p<0.001). Furthermore, patients who had received prestenting
had a significantly shorter hospital stay (median, 3 vs. 2 days, p<0.001) and
higher rates of stone clearance (83.0 vs. 69.7%, p=0.001). CONCLUSION: According
to our retrospective monocentric analysis, prestenting may significantly reduce
the risk of complications as well as intra-/post-URS restenting and can increase
the rate of complete stone clearance.
PMID- 25123562
TI - Additive effect of elcatonin to risedronate for chronic back pain and quality of
life in postmenopausal women with osteoporosis: a randomized controlled trial.
AB - Calcitonin has been reported to reduce acute and chronic back pain in
osteoporotic patients. The additive effect of calcitonin with a bisphosphonate on
chronic back pain remains unclear. The purpose of this study was to evaluate the
effect of combining elcatonin (eel calcitonin) with risedronate for patients with
chronic back pain. Forty-five postmenopausal women diagnosed as having
osteoporosis with chronic back pain persisting for more than 3 months, after
excluding women with fresh vertebral fractures within the last 6 months, were
randomly allocated to a risedronate group (risedronate alone, n = 22) and a
combined group (risedronate and elcatonin, n = 23). The study period was 6
months. Pain was evaluated with a visual analogue scale (VAS) and the Roland
Morris questionnaire (RDQ). Back extensor strength, bone mineral density, and
quality of life on the SF-36 and the Japanese osteoporosis quality of life score
were also evaluated. Significant improvements were found in the combined group
for VAS at final follow-up compared with baseline and 3 months, mental health
status on the SF-36, and JOQOL domains for back pain and general health. The
JOQOL domain for back pain improved significantly, but no change was found in the
VAS or other domains in the risedronate group. Bone mineral density increased
significantly in the two groups, but no significant difference was found between
the groups. Back extensor strength did not change in both groups. In conclusion,
the use of elcatonin in addition to risedronate for more than 3 months reduced
chronic back pain. The additional therapy of risedronate with elcatonin may be a
useful and practical choice for the treatment of osteoporosis with chronic back
pain persisting more than 3 months.
PMID- 25123563
TI - Characteristics of patients with yellow nail syndrome and pleural effusion.
AB - Yellow nail syndrome (YNS) can be associated with a pleural effusion (PE) but the
characteristics of these patients are not well defined. We performed a systematic
review across four electronic databases for studies reporting clinical findings,
PE characteristics, and most effective treatment of YNS. Case descriptions and
retrospective studies were included, unrestricted by year of publication. We
reviewed 112 studies (150 patients), spanning a period of nearly 50 years. The
male/female ratio was 1.2/1. The median age was 60 years (range: 0-88). Seventy
eight percent were between 41-80 years old. All cases had lymphoedema and 85.6%
had yellow nails. PEs were bilateral in 68.3%. The appearance of the fluid was
serous in 75.3%, milky in 22.3% and purulent in 3.5%. The PE was an exudate in
94.7% with lymphocytic predominance in 96% with a low count of nucleated cells.
In 61 of 66 (92.4%) of patients, pleural fluid protein values were >3 g/dL, and
typically higher than pleural fluid LDH. Pleurodesis and
decortication/pleurectomy were effective in 81.8% and 88.9% of cases,
respectively, in the treatment of symptomatic PEs. The development of YNS and PE
occurs between the fifth to eighth decade of life and is associated with
lymphoedema. The PE is usually bilateral and behaves as a lymphocyte-predominant
exudate. The most effective treatments appear to be pleurodesis and
decortication/pleurectomy.
PMID- 25123565
TI - Evidence for a novel, local acute-phase response in the bovine oviduct:
progesterone and lipopolysaccharide up-regulate alpha 1-acid-glycoprotein
expression in epithelial cells in vitro.
AB - Little is known about the local production and function of alpha 1-acid
glycoprotein (AGP), an acute-phase protein, in the female reproductive tract.
This study aimed to investigate the regulation and immune function of AGP in
cultured bovine oviduct epithelial cells. Analysis by Western blotting and
immunohistochemistry revealed that bovine oviduct tissue expresses AGP protein in
epithelial cells and the smooth muscle layer. Stimulation of bovine oviduct
epithelial cells in culture with either progesterone (1 ng/ml) or
lipopolysaccharide (LPS, 10 ng/ml) induced both mRNA expression and secretion of
AGP. Estradiol (1 ng/ml), progesterone (1 ng/ml), and luteinizing hormone (10
ng/ml), which are observed during the peri-ovulatory period in oviduct tissues
(steroids) or in circulation (luteinizing hormone), suppressed LPS-induced
expression and secretion of AGP, which in turn induced the expression of Toll
like receptor-4 (TLR-4) and interleukin-1beta (IL-1B), but suppressed TLR-2 and
tumor necrosis factor-alpha (TNFA) expression. AGP also inhibited LPS-induced TLR
2 and TNFA expression, but had no effect on LPS-induced TLR-4 and IL-1B
expression. These findings suggest that oviductal epithelial cells can
participate in antimicrobial processes through the secretion of AGP, which is
partly regulated by ovarian steroids. Moreover, oviductal AGP may regulate the
response of epithelial cells, thereby reducing the expression of the acute pro
inflammatory cytokine TNFA, which could contribute to the local homeostasis
during the acute response to endotoxin release in the oviduct's anti-infection
process.
PMID- 25123564
TI - Bedside ultrasound curriculum for medical students: report of a blended learning
curriculum implementation and validation.
AB - BACKGROUND: Medical students on clinical rotations rarely receive formal bedside
ultrasound (BUS) training. We designed, implemented, and evaluated a standardized
BUS curriculum for medical students on their Emergency Medicine (EM) rotation.
Teaching was aimed toward influencing four cognitive and psychomotor learning
domains: BUS instrumentation knowledge, image interpretation, image acquisition,
and procedural guidance. METHODS: Participants viewed three instructional Web
based tutorials on BUS instrumentation, the Focused Assessment for Sonography in
Trauma (FAST) examination and ultrasound-guided central venous catheter (CVC)
placement. Subsequently, participants attended a 3-hour hands-on training session
to discuss the same content area and practice with faculty coaches. A Web-based,
multiple-choice questionnaire was administered before and after the session.
During the final week of the rotation, students returned for skills assessments
on FAST image acquisition and CVC placement. RESULTS: Forty-five medical students
on an EM rotation were enrolled. Sonographic knowledge overall mean score
improved significantly from 66.6% (SD +/-11.2) to 85.7% (SD +/-10.0),
corresponding to a mean difference of 19.1% (95% CI 15.5-22.7; p < 0.001). There
were high pass rates for FAST (89.0%, 40/45) and CVC (96.0%, 43/45) skills
assessments. There was no significant difference between medical student posttest
and EM resident test scores 85.7% (SD +/-10.0) and 88.1% (SD +/- 7.6) (p = 0.40),
respectively. CONCLUSIONS: A formal BUS curriculum for medical students on EM
rotation positively influenced performance in several key learning domains. As
BUS competency is required for residency in EM and other specialties, medical
schools could consider routinely incorporating BUS teaching into their clinical
rotation curricula.
PMID- 25123566
TI - Progression of plasma D-dimer concentration and coagulopathies during
hospitalization in horses with colic.
AB - OBJECTIVE: To assess the progression of plasma D-dimer concentrations and
coagulation status in horses with different types of colic. DESIGN: Prospective
clinical observational study performed between March 2004 and September 2008.
SETTING: Veterinary university teaching hospital. ANIMALS: Horses admitted and
treated for colic and hospitalized for >48 hours were considered. Animals were
classified by diagnosis into medical obstructive conditions (MO), surgical
obstructive conditions (SO), inflammatory conditions, and ischemic lesions (IS).
INTERVENTIONS: Three blood samples were obtained from each horse (admission, at
24-48 h [or after surgery] and upon discharge). For each sample, plasma D-dimer
concentration, prothrombin time, activated partial thromboplastin time,
antithrombin activity, and the presence of subclinical disseminated intravascular
coagulation were determined. MEASUREMENTS AND MAIN RESULTS: When median plasma D
dimer concentration values at admission and after 24-48 hours were compared, they
were different but stable in horses with MO (1.29-1.95 nmol/L) and inflammatory
conditions (5.70-6.69 nmol/L). However, 10-fold and 5-fold increases were
observed, respectively, in SO (2.08 to 16.38 nmol/L) and IS (3.08 to 15.91
nmol/L) in the postoperative period. By 24-48 hours, the percentage of horses
with coagulopathy increased in most groups (MO, 43 to 58%; SO, 50 to 96%, IS, 53
to 90%). By the time of discharge, 87% of horses with SO problems and 89% of
horses with IS still had some form of coagulopathy documented. CONCLUSIONS:
Throughout hospitalization, horses with MO problems had less severe coagulopathy
and lower plasmatic D-dimer concentrations compared to other groups of horses. On
admission, most horses with inflammatory conditions presented with coagulopathy.
At 24-48 hours of hospitalization and following surgery, the hemostatic profile
can differ markedly when compared to admission values.
PMID- 25123567
TI - Chronic cutaneous chest wall fistula and gallstone empyema due to retained
gallstones.
AB - We report a case of a 72-year-old man who presented with a persistent pleural
effusion and painful abscess in the right lower chest wall 6 months following a
laparoscopic cholecystectomy. The patient subsequently developed a chronic
cutaneous chest wall fistula requiring a large resection and complex closure. The
complication was likely secondary to intraoperative spillage of gallstones. While
previous reports describe gallstone spillage in the abdominal cavity as benign,
this case illustrates that stones left in the abdominal cavity can potentially
lead to significant morbidity. Therefore, stones should be diligently removed
from the abdominal cavity when spillage occurs. In addition, it is important that
operative notes reflect the occurrence of stone spillage so stones may be
suspected when a patient presents with an abdominal or thoracic infection
following a cholecystectomy.
PMID- 25123568
TI - A rapidly growing lid lump.
AB - A 97-year-old woman presented with a 5-month history of a rapidly growing,
painless, left upper eyelid lesion. Examination revealed a large vascularised,
ulcerated nodule on the left upper lid, causing significant ptosis. Wide local
excision of the lesion was performed and the wound was left to heal by secondary
intention. Histology and immunohistochemistry of the lesion confirmed a diagnosis
of Merkel cell carcinoma, a rare primary malignancy of the eyelid which has
significant morbidity and mortality. Although uncommon, this diagnosis should
always be considered in any patient with a rapidly growing lid lump. In view of
the patient's age, known dementia and family wishes, the patient was managed
conservatively, with no further investigations performed. She was due to be
followed up in clinic on a regular basis, but has since died from other causes.
PMID- 25123569
TI - Septic sacroiliitis revealing an infectious endocarditis.
AB - We report the case of a 43-year-old man admitted for right hip ache and fever.
Physical examination revealed a fever, an ache at the manipulation of the
sacroiliac joint and a limitation of abduction and external rotation of the right
hip. There was no murmur in cardiac auscultation. No anomaly was found at the
conventional radiographs of the sacroiliac joint, while the pelvic MRI confirmed
a right sacroiliitis. A sacroiliac puncture with a study of synovial fluid
demonstrated the presence of Streptococcus viridans. The blood culture revealed
the same germ. Transthoracic and transoesophageal echocardiography confirmed
infectious endocarditis with vegetation in the mitral valve. He received
penicillin G and gentamicin relayed by pristinamycin because of an allergy to
penicillin G with a total duration of treatment of 40 days. His symptoms and the
laboratory and radiological tests abnormalities resolved totally with no
recurrence.
PMID- 25123570
TI - West-African trypanosomiasis in a returned traveller from Ghana: an unusual cause
of progressive neurological decline.
AB - West-African trypanosomiasis caused by Trypanosoma brucei gambiense is a rare
imported infection presenting with somnolence, lymphadenopathy and wide-ranging
neurological symptoms. A 67-year-old Caucasian man presented with a 10-month
history of cognitive deterioration, ataxic gait, somnolence and urinary
incontinence. His symptoms had progressed more rapidly over the course of a month
prior to admission. Serological testing confirmed a diagnosis of West-African
trypanosomiasis. The patient was successfully treated with eflornithine and made
a good recovery. West-African trypanosomiasis should be considered in the
differential diagnosis of unexplained cognitive decline in those with a relevant
travel history. If left untreated, the condition is universally fatal.
PMID- 25123571
TI - Isolated III cranial nerve palsies may point to primary histiocytic sarcoma.
AB - Primary histiocytic sarcoma (HS) of the central nervous system (CNS) is a rare
haematopoietic neoplasm. The inconsistent terminology and diagnostic criteria
currently used for CNS HS have complicated the appreciation of the clinical
aspects of the disease. The main differential diagnoses are non-Hodgkin's
lymphoma, reactive histiocytic proliferation, dendritic cell neoplasm,
undifferentiated carcinoma, inflammatory pseudotumour, Rosai-Dorfman disease and
abscess. The true diagnosis of CNS HS requires an extensive immunophenotypic
workup using specific histiocytic markers, such as CD163, with the exclusion of
markers of other cell lineages. This clinicopathological case report describes an
improved approach towards the differential diagnosis of CNS HS.
PMID- 25123572
TI - Oral manifestation of plantar-palmar fibromatosis.
PMID- 25123573
TI - Perivascular epithelioid cell tumour of the bladder.
AB - A 39-year-old woman presented with a long history of pelvic pain and urinary
urgency. Prior workup by her primary care doctor had been negative. The patient's
gynaecologist ultimately referred her to a urologist following an ultrasound that
revealed a possible bladder mass. MRI of the abdomen and pelvis demonstrated a 4
cm soft tissue lesion arising from the bladder. Cystoscopy showed an atypical
mass on the anterior bladder wall, and pathological examination of the TURBT
(transurethral resection of the bladder tumour) specimen revealed a perivascular
epithelioid cell tumour (PEComa) with involvement of the detrusor muscle. The
patient underwent a robotically assisted laparoscopic partial cystectomy. Final
pathology confirmed a PEComa with negative margins. The patient had an
uncomplicated postoperative course and is doing well following surgery. A
surveillance cystoscopy at 6 months showed no evidence of recurrence. This case
underscores the variability of clinical presentation of PEComas while proposing
an appropriate method of surgical management.
PMID- 25123574
TI - NK/T-cell non-Hodgkin's lymphoma with secondary haemophagocytic
lymphohistiocytosis treated with matched unrelated donor allogeneic stem cell
transplant.
PMID- 25123576
TI - Colorectal cancer screening in the American Indian/Alaska Native population:
progress and at least one new challenge.
PMID- 25123575
TI - Activity of T-DM1 in HER-2 positive central nervous system breast cancer
metastases.
AB - A 55-year-old woman with metastatic human epidermal growth factor receptor 2 (HER
2) positive breast cancer (BC) to the lungs and bones was diagnosed with central
nervous system (CNS) metastases in November 2011. The MRI showed a right parietal
lobe mass with adjacent leptomeningeal disease and several small bilateral
cerebellar metastases. She was treated with whole brain irradiation (WBI),
followed by capecitabine and lapatinib (December 2011-March 2013) and trastuzumab
and lapatinib (May 2013-August 2013). Then, the brain MRI showed progression. In
the absence of significant neurological symptoms, we postponed WBI and closely
monitored for the development of neurological symptoms. Systemic treatment with
trastuzumab emtansine (T-DM1), an antibody-drug conjugate composed of the
cytotoxic agent DM1 conjugated to trastuzumab, was initiated in September 2013 to
control systemic disease. Unexpectedly, after two cycles of treatment the brain
MRI showed a decrease in size of CNS metastases. This case report suggests
possible activity of T-DM1 in HER-2 positive BC with CNS metastases.
PMID- 25123578
TI - Differentiation and morphogenesis of the ovary and expression of gonadal
development-related genes in the protogynous hermaphroditic ricefield eel
Monopterus albus.
AB - The ovarian differentiation, morphogenesis and expression of some putative
gonadal development-related genes were analysed in the ricefield eel Monopterus
albus, a protogynous hermaphroditic teleost with a single elongate ovary. At c. 1
day post-hatching (dph), the gonadal ridge was colonized with primordial germ
cells (PGCs) at the periphery and transformed into the gonadal primordium, which
appeared to contain two germinal epithelia. At c. 7 dph, four ovarian cavities
appeared in the gonadal tissue with two in each germinal epithelial compartment,
and the indifferent gonad might have begun to differentiate into the ovary. The
oocytes at the leptotene stage in meiosis I appeared at c. 14 dph, and oocytes at
the diplotene stage at c. 30 dph. As development proceeded, the connective tissue
separating the two germinal epithelia disappeared, and two of the four ovarian
cavities collapsed into one. At 60 dph, the gonad had already taken the shape as
observed in the adults. One outer and two inner ovarian cavities could be easily
recognized, with slightly basophilic primary growth oocytes usually residing
close to the outer ovarian cavity. The expression of cyp19a1a and erb in the
early gonad was detected at 6 dph. The abundant expression of foxl2 coincided
with the up-regulation of cyp19a1a at 8 dph onwards. The expression of dmrt1
isoforms was not detectable until 8 dph for dmrt1a and dmrt1b and until 33 dph
for dmrt1d. The earlier appearance of cyp19a1a compared to dmrt1 transcripts in
the indifferent gonad may contribute to the initial differentiation of the gonad
towards the ovary in M. albus.
PMID- 25123577
TI - Neural tube defects and atypical deletion on 22q11.2.
AB - The 22q11.2 deletion syndrome (22q11.2DS) is a common microdeletion disorder.
Most of the patients show the common 3 Mb deletion but proximal 1.5 Mb deletion
and unusual deletions located outside the common deleted region, have been
detected particularly with the advance of comparative cytogenomic microarray
technologies. The individuals reported in the literature with unusual deletions
involving the 22q11 region, showed milder facial phenotypes, decreased incidence
of cardiac anomalies, and intellectual disability. We describe two sibs with an
atypical 0.8 Mb microdeletion of chromosome 22q11 who both showed
myelomeningocele and mild facial dysmorphisms. The association between neural
tube defect and the clinical diagnosis of Di George anomaly/velocardiofacial
syndrome is well documented in the literature, but not all cases had molecular
studies to determine breakpoint regions. This report helps to narrow a potential
critical region for neural tube defects associated with 22q11 deletions.
PMID- 25123579
TI - Risks of a lifetime in construction. Part II: Chronic occupational diseases.
AB - BACKGROUND: We developed working-life estimates of risk for dust-related
occupational lung disease, COPD, and hearing loss based on the experience of the
Building Trades National Medical Screening Program in order to (1) demonstrate
the value of estimates of lifetime risk, and (2) make lifetime risk estimates for
common conditions among construction workers. METHODS: Estimates of lifetime risk
were performed based on 12,742 radiographic evaluations, 12,679 spirometry tests,
and 11,793 audiograms. RESULTS: Over a 45-year working life, 16% of construction
workers developed COPD, 11% developed parenchymal radiological abnormality, and
73.8% developed hearing loss. The risk for occupationally related disease over a
lifetime in a construction trade was 2-6 times greater than the risk in non
construction workers. CONCLUSIONS: When compared with estimates from annualized
cross-sectional data, lifetime risk estimates are highly useful for risk
expression, and should help to inform stakeholders in the construction industry
as well as policy-makers about magnitudes of risk.
PMID- 25123581
TI - Pseudoporphyria following self-medication with chlorophyll.
AB - Two cases of pseudoporphyria are described in which the clinical features of
porphyria cutanea tarda occurred in the absence of abnormalities in porphyrin
metabolism. Both patients presented with skin fragility and bullae on the dorsal
aspect of the hands. The patients consumed a commercial liquid chlorophyll drink
in which we detected fluorescent compounds with characteristics typical of
previously described chlorophyll derived photosensitisers.
PMID- 25123582
TI - Interaction of a novel antimicrobial peptide isolated from the venom of solitary
bee Colletes daviesanus with phospholipid vesicles and Escherichia coli cells.
AB - The peptide named codesane (COD), consisting of 18 amino acid residues and
isolated from the venom of wild bee Colletes daviesanus (Hymenoptera :
Colletidae), falls into the category of cationic alpha-helical amphipathic
antimicrobial peptides. In our investigations, synthetic COD exhibited
antimicrobial activity against Gram-positive and Gram-negative bacteria and
Candida albicans but also noticeable hemolytic activity. COD and its analogs
(collectively referred to as CODs) were studied for the mechanism of their
action. The interaction of CODs with liposomes led to significant leakage of
calcein entrapped in bacterial membrane-mimicking large unilamellar vesicles made
preferentially from anionic phospholipids while no calcein leakage was observed
from zwitterionic liposomes mimicking membranes of erythrocytes. The preference
of CODs for anionic phospholipids was also established by the blue shift in the
tryptophan emission spectra maxima when the interactions of tryptophan-containing
COD analogs with liposomes were examined. Those results were in agreement with
the antimicrobial and hemolytic activities of CODs. Moreover, we found that the
studied peptides permeated both the outer and inner cytoplasmic membranes of
Escherichia coli. This was determined by measuring changes in the fluorescence of
probe N-phenyl-1-naphthylamine and detecting cytoplasmic beta-galactosidase
released during the interaction of peptides with E. coli cells. Transmission
electron microscopy revealed that treatment of E. coli with one of the COD
analogs caused leakage of bacterial content mainly from the septal areas of the
cells.
PMID- 25123583
TI - Quantitative and qualitative morphologic, cytochemical, and ultrastructural
characteristics of blood cells in captive Asian water monitors.
AB - BACKGROUND: The Asian water monitor (Varanus salvator) is the most common monitor
lizard in Thailand. Reported data regarding hematology and morphology of blood
cells for this species are scarce. OBJECTIVES: The objective of this study was to
assess routine hematologic variables and characterize the morphology,
cytochemical staining, and ultrastructural features of blood cells in the Asian
water monitor. METHODS: Blood samples from 55 monitors (22 males and 33 females)
were obtained for a CBC. Cytochemical staining (Sudan black B [SBB], peroxidase
[PO], alpha-naphthyl acetate esterase [ANAE], and beta-glucuronidase [BG]), and
scanning and transmission electron microscopy were performed using standard
methods. RESULTS: Determined mean (range) hematologic results of all monitors
included PCV 0.32 L/L (0.20-0.44 L/L), HGB 106 g/L (62-157 g/L), WBC 15.9 * 10(9)
/L (4.0-34.0 * 10(9) /L), heterophil 6.3 * 10(9) /L (1.5-17.1 * 10(9) /L,
azurophil 2.6 * 10(9) /L (0.7-9.5 * 10(9) /L), basophil 0.1 (0.1-0.5 * 10(9) /L),
lymphocyte 6.8 * 10(9) /L (0.5-13.1 * 10(9) /L), and monocyte 0.2 * 10(9) /L
(0.04-1 * 10(9) /L) counts. Heterophils and basophils stained strongly positive
with SBB, ANAE, and BG. Heterophils contained 2 types of granules, round SBB
positive and PO-negative granules, and electron-dense, large rod-shaped granules.
Gamonts of Hepatozoon sp. were found in <1% RBC of 43 monitors. There was no
significant difference between hematologic variables in Hepatozoon-positive and
negative monitors. CONCLUSION: Heterophils in Asian water monitors may also
function as eosinophils based on cytochemical and ultrastructural features. The
quantitative results may be used as base for further studies in healthy and
diseased Asian water monitors.
PMID- 25123584
TI - Revaluation of geometric cues reduces landmark discrimination via within-compound
associations.
AB - Rats were trained in a triangular water maze in which a compound of geometric and
landmark cues indicated the position of a submerged platform. Rats that then
underwent revaluation of the geometric cues in the absence of the landmarks
subsequently failed to discriminate between the landmarks. In contrast, those
animals that received geometry training consistent with their previous experience
of the geometry-landmark compound continued to discriminate the landmark cues.
The experiment showed that within-compound associations had formed between the
geometry and landmarks, and that representations of absent geometric cues could
be evoked via presentation of the landmark cues alone. We argue that these evoked
representations of the absent geometry cues can counteract any overshadowing of
the landmark by geometry cues, and may sometimes result in potentiation. The
results of this study do not support theories of cue-competition failure based on
independent cue processing, but remain readily explicable by appeal to an account
based on within-compound associations.
PMID- 25123585
TI - Thermal conductivity improvement of surface-enhanced polyetherimide (PEI)
composites using polyimide-coated h-BN particles.
AB - In this study, we investigated the thermal conductivities and mechanical
properties of polyetherimide (PEI) composites using polyimide (PI)-coated h-BN
(PI-BN) particles. We found that PI-coated h-BN effectively increased adhesion
with the PEI matrix, imparting enhanced mechanical and thermal stability and
thermal conductivity with increasing BN content. The thermal conductivity of the
PEI composite containing 60 wt% PI-BN was 3.3 W m(-1) K(-1), while the thermal
conductivity of the PEI/BN composite without modification was 2.6 W m(-1) K(-1).
The PEI/PI-BN composites show higher impact strengths than the PEI/BN composites
because of less BN particle agglomeration and good wettability between PEI and h
BN. The results indicate that the PI-coated BN incorporated into the PEI matrix
effectively enhances the thermal conductivity and mechanical properties of the
PEI composites.
PMID- 25123587
TI - Techniques to measure sorption and migration between small molecules and
packaging. A critical review.
AB - The mass transfer parameters diffusion and sorption in food and packaging or
between them are the key parameters for assessing a food product's shelf-life in
reference to consumer safety. This has become of paramount importance owing to
the legislations set by the regulated markets. The technical capabilities that
can be exploited for analyzing product-package interactions have been growing
rapidly. Different techniques categorized according to the state of the diffusant
(gas or liquid) in contact with the packaging material are emphasized in this
review. Depending on the diffusant and on the analytical question under review,
the different ways to study sorption and/or migration are presented and compared.
Some examples have been suggested to reach the best possible choice, consisting
of a single technique or a combination of different approaches.
PMID- 25123588
TI - Mechanochromic luminescence of fluorenyl-substituted ethylenes.
AB - It has been reported several times that some organic luminogens with aggregation
induced emission (AIE) characteristics exhibit the abnormal phenomenon of
crystallization-induced blueshift fluorescence, which makes them suitable for
utilization as luminescence color-switching materials. Because of the attractive
application potential and the numerous underlying structure-property
relationships in such materials, we investigated a series of fluorenyl-containing
tetrasubstituted ethylenes for their novel optical properties and structural
features. The dyes show morphology-dependent luminescence. Their emission color
can be switched between green and blue by means of mechanical grinding and
solvent fuming. The transformation between crystalline and amorphous accounts for
the luminescence changing. Through single-crystal and X-ray diffraction (XRD)
analysis, the twisted molecular geometries and loose packing motifs in the
crystalline samples are believed to be the intrinsic origin of the external
stimuli-induced structural transformation.
PMID- 25123586
TI - High-resolution crystal structure and IgE recognition of the major grass pollen
allergen Phl p 3.
AB - BACKGROUND: Group 2 and 3 grass pollen allergens are major allergens with high
allergenic activity and exhibit structural similarity with the C-terminal portion
of major group 1 allergens. In this study, we aimed to determine the crystal
structure of timothy grass pollen allergen, Phl p 3, and to study its IgE
recognition and cross-reactivity with group 2 and group 1 allergens. METHODS: The
three-dimensional structure of Phl p 3 was solved by X-ray crystallography and
compared with the structures of group 1 and 2 grass pollen allergens. Cross
reactivity was studied using a human monoclonal antibody which inhibits allergic
patients' IgE binding and by IgE inhibition experiments with patients' sera.
Conformational Phl p 3 IgE epitopes were predicted with the algorithm SPADE, and
Phl p 3 variants containing single point mutations in the predicted IgE binding
sites were produced to analyze allergic patients' IgE binding. RESULTS: Phl p 3
is a globular beta-sandwich protein showing structural similarity to Phl p 2 and
the Phl p 1-C-terminal domain. Phl p 3 showed IgE cross-reactivity with group 2
allergens but not with group 1 allergens. SPADE identified two conformational IgE
epitope-containing areas, of which one overlaps with the epitope defined by the
monoclonal antibody. The mutation of arginine 68 to alanine completely abolished
binding of the blocking antibody. This mutation and a mutation of D13 in the
predicted second IgE epitope area also reduced allergic patients' IgE binding.
CONCLUSION: Group 3 and group 2 grass pollen allergens are cross-reactive
allergens containing conformational IgE epitopes. They lack relevant IgE cross
reactivity with group 1 allergens and therefore need to be included in diagnostic
tests and allergen-specific treatments in addition to group 1 allergens.
PMID- 25123589
TI - An exploration of compassion focused therapy following acquired brain injury.
AB - BACKGROUND: People with acquired brain injuries (ABI) frequently experience
psychological difficulties such as anxiety and depression, which may be
underpinned and maintained by high self-criticism and shame alongside an
inability to self-soothe. Compassionate focused therapy (CFT) was developed to
address shame and self-criticism and foster the ability to self-soothe.
OBJECTIVES: This is a naturalistic evaluation with the aim of assessing the
feasibility, safety, and potential value of CFT for ABI patients with emotional
difficulties receiving neuropsychological rehabilitation. METHODS: This study
employed a mixed methods design combining self-report measures and qualitative
interviews. Twelve patients received a combination of CFT group and individual
intervention. Self-report measures of self-criticism, self-reassurance, and
symptoms of anxiety and depression were collected pre and post programme and
analysed using Wilcoxon signed rank test (N=12; five female, seven males). Follow
up data were analysed in the same manner (N=9). Interviews were conducted with
six patients and analysed using interpretative phenomenological analysis.
RESULTS: CFT was associated with significant reductions in measures of self
criticism, anxiety, and depression and an increase in the ability to reassure the
self. No adverse effects were reported. Three superordinate themes emerged from
the interviews: psychological difficulties; developing trust and finding
safeness; and a new approach. CONCLUSIONS: This study suggests that CFT is well
accepted in ABI survivors within the context of neuropsychological
rehabilitation. Furthermore, the results indicate that further research into CFT
for psychological problems after ABI is needed and that there may be key aspects,
which are specific to CFT intervention, which could reduce psychological
difficulties after ABI. PRACTITIONER POINTS: CFT appears to be a feasible
intervention for psychological problems after ABI. CFT was associated with a
reduction in symptoms of anxiety and depression and associated self-criticism, as
well as enhanced self-reassurance for ABI survivors. These ABI survivors reported
that CFT provided them with tools to manage continued psychological difficulties.
PMID- 25123590
TI - Purification and biochemical characterization of an extracellular endoglucanase
from the necrotrophic oomycete, Pythium myriotylum Dreschler.
AB - An extracellular endoglucanase (EG) that catalyzes the hydrolysis of carboxy
methyl cellulose (CMC) as substrate was purified to homogeneity from the soft-rot
causing oomycete P. myriotylum with maximum EG production observed in presence of
1% (w/v) sucrose. The enzyme designated PmEG was observed to be monomeric with a
molecular weight of 78 kDa as estimated by sodium dodecyl sulfate-polyacrylamide
gel electrophoresis (SDS-PAGE). Optimal activity of PmEG was determined at pH 5.0
and 25 degrees C with stability observed at pH extending over acidic to alkaline
ranges viz., 3.0-10.0 and thermal stability upto 75 degrees C for 1 h. Optimal
PmEG activity was obtained by addition of metal ions viz., Ca(2+) , Fe(3+) ,
Zn(2+) , Cu(2+) , Al(3+) , and also in presence of DTT and beta-mercaptoethanol
while it was inhibited by Cr(2+) . Various organic solvents, surfactants, and the
oxidant, H2 O2 had little/no effect on PmEG activity reflecting its robustness
and potential commercial significance. Kinetic constants of PmEG, Km and Vmax
were determined as 1.1 mM and 407 umol min(-1) mg(-1) protein, respectively.
Glucose was observed to cause mixed non-competitive inhibition of PmEG.
PMID- 25123591
TI - Unexpected drastic decrease in the excited-state electronic communication between
porphyrin chromophores covalently linked by a palladium(II) bridge.
AB - A dyad built up of a zinc(II) porphyrin and the corresponding free base, [Zn-Fb],
fused to N-heterocyclic carbene (NHCs) ligands, respectively acting as singlet
energy donor and acceptor, and a bridging trans-PdI2 unit, along with the
corresponding [Zn-Zn] and [Fb-Fb] dimers were prepared and investigated by
absorption and emission spectroscopy and density functional computations. Despite
favorable structural and spectroscopic parameters, unexpectedly slow singlet
energy transfer rates are measured in comparison with the predicted values by the
Forster theory and those observed for other structurally related dyads. This
observation is rationalized by the lack of large molecular orbital (MO) overlaps
between the frontier MOs of the donor and acceptor, thus preventing a double
electron exchange through the trans-PdI2 bridge, and by an electronic shielding
induced by the presence of this same linker preventing the two chromophores to
fully interact via their transition dipoles.
PMID- 25123592
TI - Boosting the power conversion efficiency of perovskite solar cells using self
organized polymeric hole extraction layers with high work function.
AB - A self-organized hole extraction layer (SOHEL) with high work function (WF) is
designed for energy level alignment with the ionization potential level of CH3
NH3 PbI3 . The SOHEL increases the built-in potential, photocurrent, and power
conversion efficiency (PCE) of CH3 NH3 PbI3 perovskite solar cells. Thus,
interface engineering of the positive electrode of solution-processed planar
heterojunction solar cells using a high-WF SOHEL is a very effective way to
achieve high device efficiency (PCE = 11.7% on glass).
PMID- 25123593
TI - Lessons from early clinical experience with the Afirma gene expression
classifier.
PMID- 25123594
TI - Estimation of regional cerebral blood flow using N-isopropyl-p-123I
iodoamphetamine acquisition data from the lungs and brain. An improved non
invasive technique.
AB - AIM: Previously, we devised a method for estimating123I labeled N-isopropyl-p
iodoamphetamine (123I IMP) arterial blood activity at 10 minutes after
intravenous injection of 123I IMP (Ca10) without any blood sampling using 123I
IMP autoradiography (ARG) acquisition data, and verified its usefulness for
quantification of regional cerebral blood flow (rCBF). In this study, we
attempted to develop an improved noninvasive method for estimating rCBF.
PATIENTS, METHODS: 123I IMP studies with 23 patients and 15O-H2O positron
emission tomography (PET) ARG studies with 20 patients were evaluated. Multiple
regression analysis was used to estimate an integral of the arterial blood counts
during the time after injection of 123I (?Ca) using parameters from the time
series of the lung counts and brain counts as the explanatory variables and the
fraction [brain single-photon emission computed tomography (SPECT) average count
/ the mean of rCBFs (mean CBF) measured by 15O-H2O PET ARG method] as the
objective variable. RESULTS: The regression equation was as follows: Estimated
?Ca = (7.09*10-3 . Cb12) - (1.57*10-4 . CbpreSPECT) + (9.48*10-5 . CbpostSPECT) +
(1.35*10-4 . L15) - (6.95*10-4 . L33) + (7.61*10-4 . L81) - (0.417), where Cb12:
brain count at 12 minutes, Cbpre-SPECT: brain count before SPECT, Cbpost-SPECT:
brain count after SPECT, L15, L33, and L81: lung count at 15, 33, and 81 seconds,
respectively. The mean CBF values (ml/min/100g) calculated using the estimated
?Ca values more closely correlated with those measured by 15O-H2O PET ARG method
(r = 0.833, p < 0.01) than those obtained by our previous method (r = 0.590, p <
0.01). CONCLUSION: The rCBFs obtained by this method approximated more accurately
to the values measured by 15O-H2O PET ARG method than those obtained by our
previous method.
PMID- 25123595
TI - Monitoring, analysis, and correction of magnetic field fluctuations in echo
planar imaging time series.
AB - PURPOSE: To assess the utility of concurrent magnetic field monitoring for
observing and correcting for variations in k-space trajectories and global
background fields that occur in single-shot echo planar imaging (EPI) time series
as typically used in functional MRI (fMRI). METHODS: Field monitoring was
performed using an array of NMR field probes operated concurrently with series of
single-shot EPI acquisitions from a static phantom. The observed fluctuations in
field evolution were analyzed in terms of their temporal and spatial behavior at
the field level as well as at the level of reconstructed image series. The
potential to correct for such fluctuations was assessed by accounting for them
upon image reconstruction. An indication of the number and relative magnitude of
underlying effects was obtained via principal component analysis. RESULTS:
Trajectory and global field variations were found to induce substantial image
fluctuations. Global field fluctuations induced standard deviations in image
intensity up to 31%. Fluctuations in the trajectory induced ghosting artifacts
with standard deviations up to 2%. Concurrent magnetic field monitoring reduced
the fluctuations in the EPI time series to a maximum of 1.2%. CONCLUSION:
Concurrent magnetic field monitoring holds the potential to improve the net
sensitivity of fMRI by reducing signal fluctuations unrelated to brain activity.
PMID- 25123596
TI - Capillary-assisted fabrication of biconcave polymeric microlenses from
microfluidic ternary emulsion droplets.
AB - In this study, a simple capillary-based approach for producing biconcave
polymeric microlenses with uniform size and shape from ternary emulsion droplets
is presented. Monodisperse ternary emulsion droplets (0.6-4.0 nL) are produced
which contain a photocurable segment of an acrylate monomer and two non-curable
segments of silicone oil (SO) by using a microfluidic sheath-flowing droplet
generator on a glass chip. The curvature radius of the interfaces separating the
droplet segments, as well as the droplet size, and production rate can be
flexibly varied by changing the flow conditions of the organic and aqueous
phases. Subsequently, off-chip suspension photopolymerization yields non
spherical polymeric microparticles with two spherical concave surfaces templated
by two SO segments at random positions. By ultraviolet light irradiation of
ternary droplets with two SO segments trapped by the interior wall of a
cylindrical microcapillary (internal diameter: 130 MUm), biconcave microlenses
can be produced with two spherical concave surfaces with a common lens axis. The
produced lenses are suitable for use as optical diverging lenses.
PMID- 25123597
TI - Survival and tolerability of liver radioembolization: a comparison of elderly and
younger patients with metastatic colorectal cancer.
AB - AIM: To evaluate the outcomes among elderly (>=70 years) and younger patients
(<70 years) with liver-dominant metastatic colorectal cancer (mCRC) who received
radioembolization (RE) as salvage therapy. METHODS: A retrospective review of 107
consecutive patients with unresectable mCRC treated with RE after failing first-
and second-line chemotherapy. RESULTS: From 2002 to 2012, 44 elderly and 63
younger (<70 years) patients received RE. Patients had similar previous extensive
chemotherapy and liver-directed interventions. Using modified Response Evaluation
Criteria in Solid Tumors (mRECIST) criteria, either a stable or a partial
radiographical response was seen in 65.8% of the younger compared with 76.5% of
the elderly patients. RE was equally well tolerated in both groups and common
procedure-related adverse events were predominantly grade 1-2 and of short
duration. No significant difference was found with regard to overall median
survival between younger [8.4 months; 95% confidence interval (CI) = 6.2-10.6] or
elderly patients (8.2 months; 95% CI = 5.9-10.5, P = 0.667). The presence of
extrahepatic disease at the time of RE was associated with a significantly worse
median survival in both groups. CONCLUSION: Radioembolization appears to be as
well tolerated and effective for the elderly as it is for younger patients with
mCRC. Age alone should not be a discriminating factor for the use of
radioembolization in the management of mCRC patients.
PMID- 25123598
TI - RIST: a potent new combination therapy for glioblastoma.
AB - Glioblastoma is a highly aggressive, common brain tumor with poor prognosis.
Therefore, this study examines a new therapeutic approach targeting oncogenic and
survival pathways combined with common chemotherapeutics. The RIST (rapamycin,
irinotecan, sunitinib, temozolomide) and the variant aRIST (alternative to
rapamycin, GDC-0941) therapy delineate growth inhibiting effects in established
glioblastoma cell lines and primary cultured patient material. These combinations
significantly decreased cell numbers and viability compared to inhibitors and
chemotherapeutics alone with aRIST being superior to RIST. Notably, RIST/aRIST
appeared to be apoptogenic evoked by reduction of anti-apoptotic protein levels
of XIAP and BCL-2, with concomitant up-regulation of pro-apoptotic protein levels
of p53 and BAX. The treatment success of RIST therapy was confirmed in an
orthotopic mouse model. This combination treatment revealed significantly
prolonged survival time and drastically reduced the tumor burden by acting anti
proliferative and pro-apoptotic. Surprisingly, in vivo, aRIST only marginally
extended survival time with tumor volumes comparable to controls. We found that
aRIST down-regulates the microvessel density suggesting an insufficient
distribution of chemotherapy. Further, alterations in different molecular modes
of action in vivo than in vitro suggest, that in vivo RIST therapy may mimic the
superior aRIST protocol's pro-apoptotic inhibition of pAKT in vitro. Of note, all
substances were administered in therapeutically relevant low doses with no
adverse side effects observed. We also provide evidence of the potential benefits
of the RIST therapy in a clinical setting. Our data indicates RIST therapy as a
novel treatment strategy for glioblastoma achieving significant anti-tumorigenic
activity avoiding high-dose chemotherapy.
PMID- 25123599
TI - A team fares well with a fair coach: Predictors of social loafing in interactive
female sport teams.
AB - The present research aimed to develop and test a theoretical model that links
players' perceived justice of the coach to a more optimal motivational climate,
which in turn increases players' team identification and cohesion, and results in
lower levels of social loafing in female sport teams. Belgian elite female
basketball, volleyball, and football players (study 1; N = 259; M(age) = 22.6)
and Norwegian world-class female handball players (study 2; N = 110; M(age) =
22.8) completed questionnaires assessing players' perceived justice (distributive
and procedural), motivational climate, team identification, team cohesion (task
and social), and social loafing (perceived and self-reported). In both studies,
confirmatory and exploratory path analyses indicated that perceived justice was
positively related to a mastery climate (P < 0.05) and negatively to a
performance climate (P < 0.05). In turn, a mastery climate was linked to
increased levels of team identification (P < 0.05) and task cohesion (P < 0.05).
Consequently, players' perceived and self-reported social loafing decreased (P <
0.05). The findings of both independent studies demonstrated the impact of
coaches' fairness, and consequently, the motivational climate created by the
coach on the optimal functioning of female sport teams.
PMID- 25123600
TI - Weight changes in obese adults 6-months after discontinuation of double-blind
zonisamide or placebo treatment.
AB - We evaluated weight changes in obese patients at 6-months after they ended
participation in a 12-month randomised controlled trial in which they received
daily placebo, zonisamide 200 mg or zonisamide 400 mg, in addition to lifestyle
counselling. Of the originally randomised 225 patients, 218 completed month-12
when study interventions were discontinued. For the 154 patients who returned for
6-month follow-up off-treatment, weight changes between month-12 and month-18 for
placebo (n = 53), zonisamide 200 mg (n = 49) and zonisamide 400 mg groups (n =
52) were 0.5 kg [95% confidence interval (CI), -0.8 to 1.8; 0.7%], 1.5 kg (0.2
2.8; 1.6%; p = 0.26 vs. placebo) and 2.4 kg (1.1-3.7; 2.6%; p = 0.04 vs.
placebo), respectively. Our results suggest that although zonisamide 400 mg daily
for 12-months resulted in greater weight loss than with placebo, weight regain
after discontinuation of interventions was greater in the zonisamide 400 mg group
than placebo group.
PMID- 25123601
TI - Different roles for p16(INK) (4a) -Rb pathway and INK4a/ARF methylation between
adenocarcinomas of gastric cardia and distal stomach.
AB - BACKGROUND AND AIM: The incidence of distal gastric adenocarcinoma has
significantly decreased, but gastric cardia adenocarcinoma has been on the rise.
Cardia adenocarcinoma might be a specific entity distinct from the carcinoma of
the rest stomach. The aim was to explore putative differences in p16(INK) (4a)
retinoblastoma (Rb) pathway and INK4a/ARF methylation between gastric cardia and
distal adenocarcinomas. METHODS: Ninety-six cardia adenocarcinomas and 79 distal
samples were analyzed for comparing p16(INK) (4a) -Rb expressions, INK4a/ARF
deletion, and methylation using immunohistochemistry, polymerase chain reaction,
and methylation-specific polymerase chain reaction. RESULTS: The expression of
p16(INK) (4a) in cardia adenocarcinoma (43.2%) was significantly lower than in
distal cases (75.0%, P < 0.05). As well, cardia adenocarcinoma showed lower
expression of p14(ARF) compared with distal cases (34.1% vs 57.5%, P < 0.05). The
incidence of p16(INK) (4a) deletion was 20.5% and 15.0%, while p14(ARF) deletion
was 18.2% and 10.0% in cardia and distal adenocarcinomas, respectively, showing
no significant differences between two entities. However, the incidences of
p14(ARF) and p16(INK) (4a) methylation in cardia adenocarcinoma were
significantly higher than in distal samples (p14(ARF) : 61.5% vs 43.6%; p16(INK)
(4a) : 73.1% vs 51.3%, P < 0.05). INK4a/ARF methylations were more prevalent in
poorly differentiated cardia carcinoma compared with poorly differentiated distal
cases. CONCLUSIONS: There were differences in p16(INK) (4a) -Rb immunotypes and
INK4a/ARF methylation between two entities, indicating that cardia adenocarcinoma
may be different in cell proliferation, differentiation, and gene biomarkers
compared with distal gastric adenocarcinoma.
PMID- 25123602
TI - Automated lipid membrane formation using a polydimethylsiloxane film for ion
channel measurements.
AB - A black lipid membrane (BLM) is a powerful platform for studying the
electrophysiology of cell membranes as well as transmembrane proteins. However,
BLMs have disadvantages in terms of stability, accessibility, and
transportability, which preclude their industrial applications. To resolve these
issues, frozen membrane precursor (MP) was devised to improve the
transportability and storability of BLMs. As described previously, MP is a
storable and transportable platform that can be delivered to the point-of-use,
where BLMs are automatically formed upon thawing at room temperature. However, MP
has an inconsistent thinning-out time, ranging from 30 min to 24 h, as well as a
low success rate of BLM formation (~27%), which make it undesirable for practical
use. In our study, polydimethylsiloxane (PDMS) was introduced as a replacement
for conventionally used Teflon film to control thinning-out time. As such, we
used a PDMS thin-film, a porous-structured hydrophobic polymer, and squalene, a
high viscosity solvent, to facilitate membrane formation, whereas the absorption
rates of solvents were controlled to achieve consistent BLM formation time. We
successfully reduced thinning-out time down to <1 h as well as enhanced the
success rate of BLM formation to greater than 80%. Moreover, we demonstrated the
feasibility of our platform for use in drug screening using gramicidin A and
guanidine.
PMID- 25123603
TI - Predictive value of apoptotic microparticles to mononuclear progenitor cells
ratio in advanced chronic heart failure patients.
AB - BACKGROUND: Acutely decompensated chronic heart failure (ADHF) is considered a
life-threatening event. Despite contemporary treatment strategies of ADHF,
frequent recurrent hospitalizations due to other cardiovascular reasons after
discharge of patients from hospital occur. The objective of the study was to
examine the prognostic value of circulating endothelial-derived apoptotic
microparticles (EMPs) to mononuclear progenitor cells (MPCs) ratio for post
discharge patients with clinical stabilization after ischemic ADHF. METHODS: We
consecutively enrolled 136 patients (62 male) with coronary artery disease (CAD)
admitted with a primary diagnosis of ADHF. All patients gave written informed
consent for participation in the study. At baseline, all enrolled patients were
hemodynamically stable and they had New York Heart Association (NYHA) III/IV
classes of ischemic chronic heart failure (CHF). Observation period started at
discharge from the hospital and was up to 3 years. Flow cytometry analysis for
quantifying the number of EMPs and angiogenic MPCs was used. RESULTS: Calculated
EMP to MPC ratios in survivor and dead patient cohort were 8.4 (95% CI=7.6-9.2)
and 78.9 (95% CI=53.0-116.6), respectively (p=0.001). MPCs, EMPs, NYHA class, N
terminal pro-brain natriuretic peptide (NT-proBNP) and increased NT-proBNP>30%
within 24-84h of admission period remained statistically significant for all
cause mortality, CHF-related death, and CHF-related rehospitalization, whereas
left ventricular ejection fraction and high-sensitivity C-reactive protein for
all variables did not. We found that the addition of EPMs to MPCs ratio to the
ABC model (NT-pro-BNP, increased NT-pro-BNP>30%) improved the relative integrated
discrimination indices by 19.6% for all-cause mortality, by 21.7% for CHF-related
death, and by 19.5% for CHF-related rehospitalization. CONCLUSION: We
demonstrated that EMP to MPC ratio is considered an important indicator of an
imbalance between angiogenic and apoptotic responses with possible relation to
cardiovascular outcomes in post-discharge patients with clinical stabilization
after ischemic ADHF.
PMID- 25123604
TI - Gender differences in the clinical features of hypertrophic cardiomyopathy caused
by cardiac myosin-binding protein C gene mutations.
AB - BACKGROUND: Although gender may be one of the important factors modifying
phenotypic expression in hypertrophic cardiomyopathy (HCM), there has been little
information on it. METHODS AND RESULTS: We investigated gender differences in the
clinical features of HCM caused by cardiac myosin-binding protein C gene (MYBPC3)
mutations. Sixty-one subjects (28 families) carrying MYBPC3 mutations were
studied. Of the 61 subjects with MYBPC3 mutations, 50 patients including 23
female patients were phenotype-positive by echocardiography. Disease penetrance
in subjects aged <=40 years old was 92% in males and 67% in females. Females
showed delayed onset of left ventricular hypertrophy compared with males in
subjects who were genotype-positive. Female patients were more symptomatic at
diagnosis than were males (mean New York Heart Association class: 1.7+/-0.8
versus 1.2+/-0.4, p=0.012). From a longitudinal point of view by age, no
significant gender difference in cardiovascular deaths or cardiovascular events
was found. During the follow-up period after diagnosis of HCM (13+/-8 years),
female patients who were phenotype-positive had significantly more frequent heart
failure events than did phenotypically affected male patients (p=0.028).
CONCLUSIONS: Although females with MYBPC3 mutations showed later onset of the
disease, female patients were more symptomatic at diagnosis and had more frequent
heart failure events once they had developed hypertrophy.
PMID- 25123605
TI - The Equivalence of Remote Electronic and Paper Patient Reported Outcome (PRO)
Collection.
AB - Individual patient level Patient Reported Outcomes (PROs) are increasingly
important in clinical practice. Web-based collection enables clinicians to
remotely collect scores at regular intervals, away from the clinic setting. In
this randomized crossover study, 47 patients, having undergone hip surgery, were
allocated to two groups. Group 1 completed the web-based scores followed by the
paper equivalents one week later; Group 2 completed the scores the other way
around. The Intraclass Correlation Coefficient (ICC) for the Oxford Hip Score was
0.99, 0.98 to 0.99 (ICC, 95% CI) and the ICCs for the other scores were between
0.95 and 0.97. We conclude that remote ePRO collection using this web-based
system reveals excellent equivalence to paper PRO collection of the Oxford Hip,
McCarthy, UCLA and howRu scores.
PMID- 25123606
TI - Knee joint biomechanics and neuromuscular control during gait before and after
total knee arthroplasty are sex-specific.
AB - The future of total knee arthroplasty (TKA) surgery will involve planning that
incorporates more patient-specific characteristics. Despite known biological,
morphological, and functional differences between men and women, there has been
little investigation into knee joint biomechanical and neuromuscular differences
between men and women with osteoarthritis, and none that have examined sex
specific biomechanical and neuromuscular responses to TKA surgery. The objective
of this study was to examine sex-associated differences in knee kinematics,
kinetics and neuromuscular patterns during gait before and after TKA. Fifty-two
patients with end-stage knee OA (28 women, 24 men) underwent gait and
neuromuscular analysis within the week prior to and one year after surgery. A
number of sex-specific differences were identified which suggest a different
manifestation of end-stage knee OA between the sexes.
PMID- 25123607
TI - Reply to letter to the editor on "Simultaneous bilateral total knee arthroplasty
in octogenarians: can it be safe and effective?".
PMID- 25123608
TI - Nurses' choice of clinical field in early career.
AB - AIM: To investigate how undergraduate nursing students' perceived professional
qualifications and job values relate to their choice of clinical field after
graduation, particularly about employment in care of older people and psychiatric
fields. BACKGROUND: In the light of greater demand for highly qualified nurses,
it is important to understand how professional qualifications and job values
relate to career choices. DESIGN: A quantitative longitudinal study of 290
undergraduate nursing students based on a questionnaire survey and register data.
METHODS: Data were analysed by multinomial logistic regression analyses. The
questionnaire was distributed to all undergraduate nursing students during the
final semester of study at two university colleges in Norway (N = 411) to collect
the students' perceived professional qualifications and job values (2001).
Register data on clinical fields after graduation (2002-2006) were merged into
the survey data in 2008 (Statistics Norway). RESULTS: The tendency among
undergraduate nursing students to choose care of older people rather than general
hospital care after graduation increases as their score on altruism decreases,
but is not correlated with their score on theoretical knowledge. The tendency to
choose psychiatric fields rather than general hospital care increases with an
increasing score on perceived practical skills and decreases with an increasing
score on perceived theoretical knowledge. CONCLUSION: The choice of clinical
field after graduation correlates with undergraduate nursing students' perceived
professional qualifications and job values.
PMID- 25123609
TI - The decalog of long non-coding RNA involvement in cancer diagnosis and
monitoring.
AB - Long non-coding RNAs (lncRNAs) are transcripts without protein-coding capacity;
initially regarded as "transcriptional noise", lately they have emerged as
essential factors in both cell biology and mechanisms of disease. In this
article, we present basic knowledge of lncRNA molecular mechanisms, associated
physiological processes and cancer association, as well as their diagnostic and
therapeutic value in the form of a decalog: (1) Non-coding RNAs (ncRNAs) are
transcripts without protein-coding capacity divided by size (short and long
ncRNAs), function (housekeeping RNA and regulatory RNA) and direction of
transcription (sense/antisense, bidirectional, intronic and intergenic),
containing a broad range of molecules with diverse properties and functions, such
as messenger RNA, transfer RNA, microRNA and long non-coding RNAs. (2) Long non
coding RNAs are implicated in many molecular mechanisms, such as transcriptional
regulation, post-transcriptional regulation and processing of other short ncRNAs.
(3) Long non-coding RNAs play an important role in many physiological processes
such as X-chromosome inactivation, cell differentiation, immune response and
apoptosis. (4) Long non-coding RNAs have been linked to hallmarks of cancer: (a)
sustaining proliferative signaling; (b) evading growth suppressors; (c) enabling
replicative immortality; (d) activating invasion and metastasis; (e) inducing
angiogenesis; (f) resisting cell death; and (g) reprogramming energy metabolism.
(5) Regarding their impact on cancer cells, lncRNAs are divided into two groups:
oncogenic and tumor-suppressor lncRNAs. (6) Studies of lncRNA involvement in
cancer usually analyze deregulated expression patterns at the RNA level as well
as the effects of single nucleotide polymorphisms and copy number variations at
the DNA level. (7) Long non-coding RNAs have potential as novel biomarkers due to
tissue-specific expression patterns, efficient detection in body fluids and high
stability. (8) LncRNAs serve as novel biomarkers for diagnostic, prognostic and
monitoring purposes. (9) Tissue specificity of lncRNAs enables the development of
selective therapeutic options. (10) Long non-coding RNAs are emerging as
commercial biomarkers and therapeutic agents.
PMID- 25123610
TI - Serum soluble toll-like receptor 2: a novel biomarker for systemic lupus
erythematosus disease activity and lupus-related cardiovascular dysfunction.
AB - AIM: To assess the serum levels of soluble toll-like receptor (sTLR2) as an
endogenous negative regulator of TLR2 signaling in systemic lupus erythematosus
(SLE) patients, to investigate the correlation between sTLR2 and SLE disease
activity index (SELDAI), SLE-related cardiovascular risk factors and ventricular
dysfunction and to evaluate the effect of different therapeutic regimens on serum
sTLR2 levels. METHODS: Ninety-six SLE patients, along with 30 healthy controls,
were enrolled in the study. Echocardiography measurements were performed. Serum
levels of (sTLR2) were measured using enzyme-linked immunosorbent assay (ELISA).
Serum lipid profiles, uric acid and creatinine were also detected. RESULTS: Mean
serum levels of sTLR2 in SLE patients was 3.98 +/- 4.4 ng/mL, which was
significantly decreased as compared with that of the control group (11.3 +/- 4.9
ng/mL; P < 0.0001). sTLR2 was negatively correlated with SELDAI, low-density
lipoprotein (LDL) and left ventricular diastolic dysfunction. sTLR2 levels were
increased in patients receiving hydroxychloroquine, statins and corticosteroids.
CONCLUSION: Serum sTLR2 can attenuate disease activity and negatively impact left
ventricular diastolic dysfunction and hypercholersterelemia in SLE patients.
Statins, corticosteroids and chloroquine increase sTLR2 levels.
PMID- 25123611
TI - Multisystemic toxoplasmosis associated with a type II-like Toxoplasma gondii
strain in a New Zealand fur seal (Arctocephalus forsteri) from New South Wales,
Australia.
AB - We report the first confirmed case of toxoplasmosis in an Australian pinniped.
Presence of Toxoplasma gondii DNA was detected in the brain of a free-ranging
subadult New Zealand fur seal (Arctocephalus forsteri) with nonsuppurative
meningoencephalitis, hypophysitis, posterior uveitis, retrobulbar cellulitis, and
myocarditis associated with protozoan cysts and tachyzoites. The emaciated seal
stranded moribund on a beach in northern Sydney in New South Wales.
Histopathology coupled with specific immunohistochemistry and PCR assays
confirmed the presence of T. gondii. The T. gondii sample (NZfs8825) identified
in this study has an identical genotype as the type II (ToxoDB PCR-RFLP genotype
#1) based on the direct sequencing and virtual RFLP of multilocus DNA markers
including SAG1, 5'- and 3'-SAG2, alt.SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358,
PK1, and Apico. Direct sequencing of T. gondii B1 DNA marker from the T. gondii
sample (NZfs8825) identified a type II-like strain, based on presence of non
archetypal B1 gene polymorphisms previously reported as unique to Australia. This
study suggests that T. gondii oocysts originating from mainland Australia, which
has a large population of feral cats, may act as a disease threat to native
marine fauna. Therefore, emerging toxoplasmosis in the Arctic has a relevant
parallel in the Southern Ocean within Australian waters with yet unknown
relevance to Antarctica.
PMID- 25123612
TI - Susceptibility of chickens (Gallus gallus domesticus) to Trichinella
patagoniensis.
AB - Trichinella spp. is a genus of parasites that is widespread all over the world.
In Argentina, T. spiralis was for years the only species involved in human and
animal outbreaks. During the last decade, T. patagoniensis, a new Trichinella
species, was discovered in Argentina. Up to now, this species has only been found
in cougars (Puma concolor). Experimental infections in pigs, cats, mice and rats
with this new genotype showed that cats and mice were the most susceptible hosts.
The aim of the present work was to evaluate the susceptibility of chickens to
infection with T. patagoniensis. In order to study the intestinal and muscular
phase, and the histopathological changes, 27 Leghorn chickens were inoculated per
os with 1000 muscle larvae of T. patagoniensis and were euthanized on days 4, 5,
6, 7, 11, 14, 21, 28 and 35. Adult worms of T. patagoniensis were recovered from
the small intestine of chickens up to day 14p.i. Gross examination of small
intestine showed a moderate congestive appearance. Microscopically, an
inflammatory response with lymphocytes and eosinophils in lamina propria, slight
hyperemia, oedema and some haemorrhagic areas were detected. Lesions observed in
chickens were similar to those described in different animal species during the
intestinal phase. No muscular larvae were recovered from the muscle samples.
These results suggest that T. patagoniensis is not capable to complete its entire
life cycle in chickens.
PMID- 25123613
TI - Daily peer review of abnormal cervical smears in the assessment of individual
practice as an additional method of internal quality control.
AB - OBJECTIVE: An important internal quality control system used in the Cancer
Prevention and Research Institute cytopathology laboratory in Florence is the
peer review procedure, based on the review of all abnormal cytological smears
which routinely emerge. Peer review is an important training opportunity for all
cytologists, especially for those with less experience. This article shows the
results of the peer review procedure. METHODS: Of the 63 754 Papanicolaou (Pap)
smears screened in 2011, 1086 were considered to be abnormal [at least atypical
squamous cells of undetermined significance (ASC-US+)] on primary screening
(selected by a single cytologist) and were subjected to the peer review
procedure. The overall performance of the laboratory's cytologists was evaluated
using a multiple rater analysis and the comparison of each cytologist with the
final diagnosis. Further, the agreement was assessed by means of Cohen's kappa
and weighted kappa statistics. RESULTS: In general, a moderate/substantial level
of agreement between the ten cytologists and the final diagnoses was evident.
Kappa values for each reader compared with the final diagnosis ranged from 0.54
to 0.69. The overall kappa value was 0.62 [95% confidence interval (CI), 0.58
0.66] and overall weighted kappa value was 0.76 (95% CI, 0.74-0.79). The category
specific agreement showed the lowest values for atypical squamous cells, cannot
exclude high-grade squamous intraepithelial lesion (ASC-H). CONCLUSION: In
summary, peer review represents an important internal quality control in the
evaluation and improvement of inter-observer agreement and of the functioning of
the laboratory as a whole. Multi-head microscope sessions may improve
particularly the reproducibility of borderline diagnoses and, above all, can be
an important training contribution for cytologists.
PMID- 25123615
TI - How would you recognise a good review?
PMID- 25123614
TI - Calcified amorphous tumors (CATs) of the heart.
AB - Intracavitary cardiac masses include neoplastic and nonneoplastic masses, which
may share overlapping clinical symptomatology, physical examination findings, and
or imaging characteristics. Definitive diagnosis of a cardiac mass is usually
made on surgical excision and histological examination. In this article, we focus
on one of the rare nonneoplastic cardiac mass, namely, calcified amorphous
tumors. We present a series of three patients, an 80-year-old female who
presented to the hospital for evaluation of a near syncope event, a 69-year-old
female who presented for evaluation of palpitations, and a 60-year-old female who
presented for evaluation of shortness of breath, who were found to have calcified
amorphous tumors. We have also provided a relevant review of the literature on
this topic.
PMID- 25123617
TI - Falls in rural and remote community dwelling older adults: a review of the
literature.
AB - OBJECTIVE: Falls in older adults represent a significant challenge in Australia;
however, the focus is often on urban-dwelling older adults. The aim of this
review was to explore the literature on falls epidemiology and falls prevention
interventions (FPI). DESIGN: A literature review was conducted searching Medline,
Scopus, Social Sciences Citation Index, Google Scholar, Google and the Australian
Institute of Health and Welfare publication catalogue. SETTING: Rural and remote
Australia. PARTICIPANTS: Rural and remote community dwelling Australians aged 50
years and older. INTERVENTION: Literature review. MAIN OUTCOME MEASURES: Falls
epidemiology and effective falls prevention interventions. RESULTS: Twenty
references were identified: 14 related to falls epidemiology and 7 to FPI. No
significant differences were found between rural, remote and major cities
residents in relation to falls hospitalisation, falls mortality or fall-related
injuries sustained. There are a wide assortment of health professionals and non
health professionals who are involved in providing FPI in rural and remote
Australia. However, there was limited information on the effectiveness of these
interventions in influencing falls outcomes. CONCLUSION: Few studies explored
falls and their prevention in rural and remote Australia. The limited literature
on the topic suggests that a change in focus to one that utilises existing
services and resources will be required to create sustainable outcomes. Four
areas are proposed for concentrated effort to reduce the impact of fall-related
injury in rural and remote Australia: integration and collaboration among health
professionals, promotion of physical activity across the lifespan, community
involvement and ownership of interventions, and evaluation and publication of
findings.
PMID- 25123618
TI - Timely access to specialist medical oncology services closer to home for rural
patients: experience from the Townsville Teleoncology Model.
AB - PROBLEM: Prior to 2009, the teleoncology model of the Townsville Cancer Centre
(TCC) did not achieve its aims of equal waiting times for rural and urban
patients and the provision of reliable, local acute cancer care. From 2007-2009,
60 new patients from Mt Isa travelled to TCC for their first consultation and
their first dose of chemotherapy. Six of these patients required inter-hospital
transfers and eight required urgent flights to attend outpatient clinics. Only
50% these rural patients (n = 30) were reviewed within one week of their
referral, compared with 90% of Townsville patients. DESIGN: A descriptive study.
SETTING: TCC provides teleoncology services to 21 rural towns; the largest is Mt
Isa, Qld. KEY MEASURES FOR IMPROVEMENT: Specialist review of 90% of urgent cases
within 24 hours, and 90% of non-urgent cases within one week of referral via
videoconferencing. A 50% reduction in inpatient inter-hospital transfers from Mt
Isa to Townsville. STRATEGIES FOR CHANGE: Employment of a half-time medical
officer and a half-time cancer care coordinator, and implementation of new
policies. EFFECTS OF CHANGE: Between 2009 and 2011, TCC provided cancer care to
70 new patients from Mt Isa. Of these new patients, 93% (65/70) were seen within
one week of referral. All 17 patients requiring urgent reviews were seen within
24 hours of referral and managed locally thus eliminating the need for inpatient
inter-hospital transfers. LESSONS LEARNT: Provision of timely acute cancer care
closer to home requires an increase in the rural case complexity and human
resources.
PMID- 25123619
TI - Rural palliative care transitions from home to hospital: carers' experiences.
AB - OBJECTIVE: To document carer perceptions of patients' transitions from community
to hospital-based palliative care in a rural setting. DESIGN: A qualitative study
using an interview method at two time points. SETTING: Rural palliative care
providers: Kyneton District Health Service and the Macedon Ranges Palliative Care
Service, Victoria. PARTICIPANTS: Six adult caregivers of six palliative care
patients who had cancer were interviewed, three of whom were male and three
female. MAIN OUTCOME MEASURES: Semistructured interviews were conducted exploring
the caregivers' decisions to transition to hospital-based care and their
perceptions of the transition to hospital and the hospital-based care these
patients received. RESULTS: Thematic analysis revealed that carers made the
decision for the patient in their care to transfer from home to hospital care.
Carers experienced the transition to hospital care positively, particularly in
relation to the communication of the patient's care needs. While communication
issues arose while in hospital, they were not related to the transitional aspects
of the palliative care service. CONCLUSIONS: The findings from this small,
exploratory study suggest that these carers benefited from the new model of rural
palliative care service provision. A large-scale, mixed-method study would enable
more generalisable findings to be established.
PMID- 25123620
TI - Predictors of rural practice location for James Cook University MBBS graduates at
postgraduate year 5.
AB - OBJECTIVE: To describe factors predicting James Cook University (JCU) medical
graduates having a rural practice location at postgraduate year (PGY) 5.
PARTICIPANTS: JCU MBBS graduates who had completed their PGY 5 in Australia (n =
260). DESIGN: Multiple logistic regression analysis involving graduates'
application data (age, gender, location of hometown, School Leaving Score,
interview score, ethnicity), undergraduate data (scholarship awarded, honours
program), and postgraduation data (internship location, specialty training
undertaken). MAIN OUTCOME MEASURE: Predictors of practice in a 'rural' town
(Australian Standard Geographic Classification Remoteness Area (ASGC-RA)) 3-5 at
PGY 5. RESULTS: Practice in a 'rural' town in PGY 5 was predicted by 'internship
in an ASGC-RA 3-5 location' (prevalence odds ratios (POR) = 3.9, P < 0.001),
'undertaken postgraduate training as a general practitioner or rural generalist'
(POR = 3.4, P < 0.001), 'hometown at application located in ASGC-RA 3-5 area'
(POR = 2.9, P = 0.023), 'Aboriginal & Torres Strait Islander ancestry' (POR =
5.6, P = 0.031), and NOT undertaken postgraduate training in surgery (POR = 5.4,
P = 0.055). CONCLUSIONS: This study provides evidence that likelihood of early
career rural medical practice in Australia is enhanced by education strategies,
such as providing rurally located internship places, supporting rural general
practice, and selecting applicants with rural origins, Aboriginal or Torres
Strait Islander ancestry, and/or a genuine interest in rural, remote, Indigenous,
and tropical medicine. This early evidence supports the proposition that
investing in rural medical education will produce an appropriately trained
medical workforce to meet the needs of rural Australia. Findings also suggest
rural workforce may be further enhanced with additional specialty training
opportunities in rural tertiary hospitals, in particular, surgery.
PMID- 25123621
TI - Undergraduate physiotherapy students' expectations and perceptions of
rural/regional clinical placements.
AB - OBJECTIVE: To explore undergraduate physiotherapy students' expectations and
preconceptions of undertaking a rural/regional clinical placement and determine
if these preconceptions differ between regional and metropolitan-based students.
DESIGN: Data was collected via focus groups and analysed via thematic analysis of
emerging themes. SETTING: All focus groups were undertaken in tutorial rooms at
the participating universities between classes at a time convenient to
participants. PARTICIPANTS: Undergraduate physiotherapy students yet to complete
a major clinical placement were invited to participate. Second year physiotherapy
students from regional and metropolitan universities were recruited to form focus
groups, allowing comparison between the two groups. Four metropolitan students
and nine regional students made up the sample size. RESULTS: Three major themes
were identified via thematic analysis of transcripts; socio-cultural factors,
education and professional factors. The significance of socio-cultural factors
was far beyond what was expected to be found. Regional students did not generally
have a more accurate perspective of rural/regional placement and voiced more
concerns about missing out on educational opportunities. CONCLUSIONS:
Rural/regional clinical educators need to be mindful of creating quality
experiences with caseloads appropriate for the specific placement's requirements.
The impact of external socio-cultural factors must be acknowledged. Supervision
strategies must be put in place to ensure students on rural/regional clinical
placements are well supported to achieve a successful outcome for student and
educator.
PMID- 25123622
TI - What is the impact of longitudinal rural medical student clerkships on clinical
supervisors and hospitals?
AB - OBJECTIVE: Studies have investigated the impact of medical students undertaking
longitudinal clerkships in General Practices; however, little is known about the
impact of students' longitudinal clerkships on clinical supervisors in the
hospital environment. This research aimed to explore the educational impacts and
benefits gained from supervisory responsibilities in a rural hospital context.
DESIGN: We assessed the impact of longitudinal clerkships using individual and
group-structured interviews. The responses were thematically analysed by the
researchers. SETTING: Two rural hospitals in Victoria, Australia. PARTICIPANTS:
Fifteen senior medical and nursing staff at two rural hospitals who supervised
year four medical students in a longitudinal clinical program. RESULTS: Thematic
analysis identified three major themes: changes to the supervisor, change in the
hospital learning culture and student usefulness. Doctors and nurses who
undertook student supervisory responsibilities reported a sense of personal
change, including increased reflective practice, improved value of professional
identity and increased enthusiasm for interprofessional learning. Supervisors
updated their clinical skills and became proactive in seeking out learning
opportunities for students. Hospitals became more vibrant learning environments
and interprofessional education enhanced teamwork. Patient care increased,
knowledge gaps filled and hospital governance, policy and procedures challenged.
CONCLUSION: The benefits of longitudinal clerkship in the rural hospital setting
provided symbiotic relationships between hospitals, students, patients and
educations provider. The interprofessional approach towards clinical supervision
enhanced supervisor learning and generated an understanding among professional
groups of each other's clinical skills, roles and values, and raised an awareness
of the importance of working collaboratively for better patient outcomes and
addressing future workforce shortages.
PMID- 25123623
TI - Bibliometric analysis on Australian rural health publications from 2006 to 2012.
AB - OBJECTIVE: To review Australian rural health (ARH) publications in PubMed from
2006 to 2012 and address ARH issues raised by the 2013 Health and Medical
Research report. DESIGN: Retrospective observational study. SETTING: Internet
based bibliometric analysis using PubMed. MEDLINE-indexed ARH publications from
2006 to 2012 were retrieved using PubMed queries. ARH publications were defined
as Australian publications that explore issues relevant to the health of the
regional, rural or remote Australian population. Two authors independently
reviewed a random sample of 5% of publications for validity. MAIN OUTCOME
MEASURES: Analysis determined country of origin (Australia); publications
relevant to the National Health Priority Areas, the 2013 National Rural Health
Alliance priority areas and Rural Clinical Schools/University Departments of
Rural Health; and journal frequencies and publication types. RESULTS: ARH
publications increased from 286 in 2006 to 393 in 2012 and made up 1.4% of all
Australian PubMed publications. Combined, the health priority areas were
addressed in 52% of ARH publications. Rural Clinical Schools/University
Departments of Rural Health articles made up 7% of ARH publications. An increase
in cohort studies, systematic reviews and reviews indicated improved quality of
articles. ARH articles were most commonly published in the Australian Journal of
Rural Health (15.9%), Rural and Remote Health (13.4%) and the Medical Journal of
Australia (6.3%). Striking a balance between broadening the queries (increasing
sensitivity) and limiting the false positives by restricting the breadth of the
queries (increasing specificity) was the main limitation. CONCLUSIONS: This
reproducible analysis, repeated at given timelines, can track the progress of ARH
publications and provide directions regarding future rural health research.
PMID- 25123624
TI - Rural patients' experiences of the open disclosure of adverse events.
AB - OBJECTIVE: To analyse rural patients' and their families' experiences of open
disclosure and offer recommendations to improve disclosure in rural areas.
DESIGN: Retrospective qualitative study based on a subset of 13 semistructured,
in-depth interviews with rural patients from a larger dataset. The larger data
set form a nationwide, multisite, retrospective-qualitative study that included
100 semistructured, in-depth interviews with 119 patients and family members who
were involved in high-severity health care incidents and incident disclosure. The
larger study is known as the '100 Patient Stories' study. Interviews were
transcribed verbatim and analysed by one analyst (D.P.) for recurrent experiences
and concerns. SETTING: Acute care. PARTICIPANTS: A sub-set of 13 of the 100
participants from the '100 Patient Stories' study who identified as experiencing
an adverse incident in a rural or regional area. MAIN OUTCOME MEASURES: Patients'
and family members' perceptions and experiences of health care incident
disclosure, as expressed in interviews. RESULTS: Rural patients and clinicians
experience additional challenges to metropolitan patients and clinicians in their
experiences of health care incidents. These additional barriers include: a lack
of resources at small hospitals; delays in diagnosis and transfer; distance
between services; and a lack of communication between providers. These challenges
impact not only upon how patients and their families experience incidents, but
also how open disclosure is implemented. CONCLUSIONS: This analysis of 13 of the
100 Patient Stories interviews provides guidance to rural health services on how
to conduct open disclosure.
PMID- 25123625
TI - Creating positive rural experiences for occupational therapy students.
PMID- 25123626
TI - DOT (directly observed therapy) in diabetes: current thought, future reality.
PMID- 25123627
TI - Do clinical pathways enhance access to evidence-based acute myocardial infarction
treatment in rural emergency departments?
PMID- 25123628
TI - Alpha-lipoic acid improves high-fat diet-induced hepatic steatosis by modulating
the transcription factors SREBP-1, FoxO1 and Nrf2 via the SIRT1/LKB1/AMPK
pathway.
AB - Understanding the mechanism by which alpha-lipoic acid supplementation has a
protective effect upon nonalcoholic fatty liver disease in vivo and in vitro may
lead to targets for preventing hepatic steatosis. Male C57BL/6J mice were fed a
normal diet, high-fat diet or high-fat diet supplemented with alpha-lipoic acid
for 24 weeks. HepG2 cells were incubated with normal medium, palmitate or alpha
lipoic acid. The lipid-lowering effects were measured. The protein expression and
distribution were analyzed by Western blot, immunoprecipitation and
immunofluorescence, respectively. We found that alpha-lipoic acid enhanced
sirtuin 1 deacetylase activity through liver kinase B1 and stimulated AMP
activated protein kinase. By activating the sirtuin 1/liver kinase B1/AMP
activated protein kinase pathway, the translocation of sterol regulatory element
binding protein-1 into the nucleus and forkhead box O1 into the cytoplasm was
prevented. Alpha-lipoic acid increased adipose triacylglycerol lipase expression
and decreased fatty acid synthase abundance. In in vivo and in vitro studies,
alpha-lipoic acid also increased nuclear NF-E2-related factor 2 levels and
downstream target amounts via the sirtuin 1 pathway. Alpha-lipoic acid eventually
reduced intrahepatic and serum triglyceride content. The protective effects of
alpha-lipoic acid on hepatic steatosis appear to be associated with the
transcription factors sterol regulatory element-binding protein-1, forkhead box
O1 and NF-E2-related factor 2.
PMID- 25123629
TI - From body shadows to bodily attention: automatic orienting of tactile attention
driven by cast shadows.
AB - Body shadows orient attention to the body-part casting the shadow. We have
investigated the automaticity of this phenomenon, by addressing its time-course
and its resistance to contextual manipulations. When targets were tactile stimuli
at the hands (Exp.1) or visual stimuli near the body-shadow (Exp.2), cueing
effects emerged regardless of the delay between shadow and target onset (100,
600, 1200, 2400ms). This suggests a fast and sustained attention orienting to
body-shadows, that involves both the space occupied by shadows (extra-personal
space) and the space the shadow refers to (own body). When target type became
unpredictable (tactile or visual), shadow-cueing effects remained robust only for
tactile targets, as visual stimuli showed no overall reliable effects, regardless
of whether they occurred near the shadow (Exp.3) or near the body (Exp.4). We
conclude that mandatory attention shifts triggered by body-shadows are limited to
tactile targets and, instead, are less automatic for visual stimuli.
PMID- 25123630
TI - Anhedonia in prolonged schizophrenia spectrum patients with relatively lower vs.
higher levels of depression disorders: associations with deficits in social
cognition and metacognition.
AB - This study has sought to explore whether there are at least two subtypes of
anhedonia in schizophrenia: one closely linked with depression and another that
occurs in the absence of depression which is related to a general paucity of
internal experience. Participants were 163 adults with schizophrenia who
completed assessments of depression, anhedonia, executive functioning, positive
and negative symptoms, social cognition and metacognition. A cluster analysis
based on participants' depression and anhedonia symptom scores produced three
groups: High Depression/High Anhedonia (n=52), Low Depression/Low Anhedonia
(n=52), and Low Depression/High Anhedonia (n=59). An ANCOVA and post hoc
comparisons controlling for positive and negative symptoms found that the Low
Depression/High Anhedonia group had poorer metacognition and social cognition
than other groups. These findings point to the possibility of a subtype of
anhedonia in schizophrenia, one occurring in the relative lesser levels of
depression, and tied to deficits in the ability to think about oneself and
others.
PMID- 25123631
TI - Multi-component reactive transport in heterogeneous media and its decoupling
solution.
AB - The multi-component reactive transport model is widely used in contaminant
transport, water-rock interaction, and other earth science fields. Since its
complexity lies in its solution, a decoupling approach is used to simplify the
model to enhance computational efficiency. A decoupling approach is presented for
heterogeneous media, and used to solve the model in this situation. The whole
domain is divided into several sub-domains due to the different reactions which
may occur and the corresponding component matrix was obtained. The boundary
between sub-domains could be divided into two parts, inflow and outflow, which
are defined as the Neumann condition and the Dirichlet one, and the concentration
of the latter could be calculated by the component in the adjacent sub-domain.
Then the models in each sub-domain can be connected and solved. Taking a
heterogeneous porous media as an example in which permanganate is partially
dissolved during the process, firstly the result obtained by this method without
considering porosity variation is compared to that from PHAST: good agreement is
achieved, then while considering the change of porosity caused by the dissolution
of the permanganate, the flow field, species concentration and porosity of the
whole domain and typical sections and points during the reaction are analysed. It
is concluded that: the decoupling approach to heterogeneous media is appropriate,
and the results from the model could reflect the variation of physical fields due
to groundwater in heterogeneous media.
PMID- 25123632
TI - Global gene expression profiling of porcine endometria on Days 12 and 16 of the
estrous cycle and pregnancy.
AB - The objective of the study was to investigate transcriptomic profile of pig
endometrium on Days 12 and 16 of pregnancy in comparison with the respective days
of the estrous cycle. Labeled complementary DNA was hybridized to Porcine Long
Oligo microarray containing 13,297 oligonucleotide probes, which represented
complementary DNA and expressed sequence tags. Statistical analysis revealed 110
differentially expressed genes (DEGs) on Day 12 of pregnancy and 179 DEGs on Day
16 of pregnancy. In silico analysis of gene function and functionality networks
revealed links between genes implicated in cell death and survival, protein
synthesis, lipid metabolism, cellular movement, tissue development, and cell-to
cell signaling. On Day 12 of pregnancy, estrogen, transforming growth factor
(TGF) beta1, and fibroblast growth factor (FGF) 2, and on Day 16 of pregnancy,
epidermal growth factor (EGF), insulin, interleukin 11 (IL-11), and FGF family
members were indicated as possible upstream regulators of several DEGs. Obtained
results showed changes in global endometrial gene expression at the time of
maternal recognition of pregnancy and embryo implantation. Additionally, these
data revealed signaling molecules, which together with E2, may evoke molecular
changes in the uterus, leading to successful pregnancy establishment.
PMID- 25123633
TI - New method for assessing hand disinfection shows that pre-operative
alcohol/chlorhexidine rub is as effective as a traditional surgical scrub.
AB - BACKGROUND: Several studies have shown that rubbing hands with an
alcohol/chlorhexidine solution provides equivalent microbial decontamination to a
conventional surgical scrub using aqueous chlorhexidine. However, the authors
believe that these studies have methodological flaws that limit their
applicability to the operating theatre environment. As such, a method was
developed to compare products in an everyday operating theatre environment using
working operating theatre personnel. AIM: To determine whether or not an
alcohol/chlorhexidine rub is as efficacious as a traditional surgical scrub using
a novel method. METHODS: Bacterial counts at baseline were collected from 20
anaesthetists using the glove juice method. Subsequently, with sequential
exchange of sterile gloves, one hand underwent a 3-min scrub using 4% aqueous
chlorhexidine, and the other hand underwent a 60-s rub with a 70% isopropyl
alcohol/0.5% chlorhexidine solution. The residual bacterial count was collected
for each hand after 30 min using the glove juice method. These counts were
converted to log10 values to compare the baseline counts of right and left hands,
and efficacy between the treatment groups. FINDINGS: Mean [+/- standard deviation
(SD)] bacterial counts at baseline were (log10) 4.42 +/- 0.81 for left hands and
4.64 +/- 0.60 for right hands (P > 0.05). The mean (+/- SD) reduction from
baseline was (log10) 1.45 +/- 0.50 for 4% chlorhexidine and 2.01 +/- 0.98 for
alcohol/chlorhexidine (P > 0.05). CONCLUSION: An alcohol/chlorhexidine hand rub
was found to be as efficacious as a traditional scrub after 30 min; this study
differs from previous work as it was undertaken in a population of practising
anaesthetists in their working environment. The McKenzie method allows baseline
and study evaluations to be performed contemporaneously on the same individual.
Each subject was his/her own control. This method offers a more clinically
relevant way to compare disinfectant solutions than standard methods.
PMID- 25123634
TI - Risk factors for mediastinitis following cardiac surgery: the importance of
managing obesity.
AB - BACKGROUND: Mediastinitis is a devastating complication of cardiac surgery.
Previous studies have often observed small populations, been retrospective in
design, and used a variety of definitions for mediastinitis. AIM: To identify
risk factors for mediastinitis, and strategies to minimize its incidence.
METHODS: A prospective cohort study of 4883 adult patients who underwent cardiac
surgery between October 2003 and February 2009, comparing pre- and peri-operative
risk factors, microbial aetiology, requirement for re-admission, length of stay
and mortality between patients with and without mediastinitis. FINDINGS: Ninety
(1.8%) patients were diagnosed with mediastinitis. Microbial aetiology was
defined for 75 patients. Staphlyocococcus aureus was the most common isolate (30
episodes; 15 due to meticillin-resistant S. aureus). Univariate analysis revealed
the following pre-operative factors associated with mediastinitis: age; body mass
index; diabetes; modified logistic European System for Cardiac Operative Risk
Evaluation score; urgent admission; and longer pre-operative stay (P < 0.05).
Associated peri-operative factors were: combined coronary artery bypass grafting
plus aortic valve replacement; longer aortic cross-clamp time; and longer
cardiopulmonary bypass time (P < 0.005). Multi-variate analysis revealed that
higher body mass index, combined coronary artery bypass grafting plus aortic
valve replacement, and older age were associated with mediastinitis (P < 0.05).
Mediastinitis was associated with re-admission to hospital, longer inpatient stay
and reduced long-term survival (P < 0.05). CONCLUSION: Mediastinitis is
associated with worse short-term outcomes (re-admission, length of stay) and
reduced long-term survival. Obesity is the only modifiable pre-operative risk
factor for mediastinitis. It may be possible to reduce risk through pre-operative
weight loss programmes before elective surgery.
PMID- 25123635
TI - Randomized experimental study to investigate the peritoneal adhesion formation of
conventional monopolar contact coagulation versus noncontact argon plasma
coagulation in a rat model.
AB - OBJECTIVE: To investigate peritoneal adhesion formation of monopolar contact
coagulation (MCC) versus noncontact argon plasma coagulation (APC) in a rat
model. DESIGN: Randomized, controlled, single-blinded animal study. SETTING:
University laboratory. ANIMAL(S): Sixteen female Wistar rats. INTERVENTION(S):
Bilateral lesions were created on the abdominal wall with MCC and APC in a
standard fashion. After 10 days, the rats were euthanized to evaluate the
peritoneal trauma sites. MAIN OUTCOME MEASURE(S): Adhesion incidence, quantity,
and quality were scored 10 days postoperatively and studied histopathologically.
RESULT(S): Average energy intake was 99.5 +/- 7.39 J for APC and 95.7 +/- 9.62 J
for monopolar contact coagulation. Incidence of adhesion formation was 50.0% for
noncontact APC and 85.4% for MCC. MCC induced significantly more vascular
adhesions. Histological evaluation revealed no significant differences regarding
average depth of lesions induced by APC and MCC. Both groups showed almost
identical morphology of necrosis and granulation tissue formation. CONCLUSION(S):
This study compares for the first time adhesion formation of MCC versus
noncontact APC in a rat model. With a similar energy intake, contact coagulation
induced a significantly higher rate of adhesion formation. APC-induced adhesions
were significantly less vascularized compared with MCC adhesions. Besides the
thermal effects of both coagulation methods, the direct mechanical contact of the
MCC electrode with the highly sensitive peritoneum is thus determined to be a
pivotal additional stimulus for adhesion formation.
PMID- 25123636
TI - Is subfertility or fertility treatment associated with long-term growth in the
offspring? A cohort study.
AB - OBJECTIVE: To study whether fertility treatment or subfertility is associated
with long-term growth in the offspring. DESIGN: A prospective follow-up study
including 1,773 singletons participating in the Lifestyle During Pregnancy Study
at the age of 5. SETTING: Research centers. PATIENT(S): A total of 3,478 mother
child pairs were sampled from the Danish National Birth Cohort, and 1,773
completed the outcome measurements. A total of 69 children were born after
fertility treatment, whereas 132 were born to subfertile parents conceiving
spontaneously but after a time to pregnancy of more than 12 months. The remaining
1,572 children were born to parents conceiving spontaneously within 12 months. At
the age of 5, the children participated in a follow-up including anthropometric
measurements. Information on important covariates with respect to family
background, maternal prenatal exposures, perinatal outcomes, and postnatal
parental lifestyle characteristics were obtained from the Danish National Birth
Cohort, the 5-year follow-up, and Danish health registers. INTERVENTION(S): None.
MAIN OUTCOME MEASURE(S): Adjusted mean differences in body weight, height, body
mass index (BMI), and head circumference at age 5. RESULT(S): Compared with
spontaneously conceived children born to fertile parents, no systematic
differences were observed for body weight, height, BMI, or head circumference at
age 5 in children conceived after fertility treatment or to subfertile parents
conceiving spontaneously. CONCLUSION(S): There were no differences in child
anthropometrics at 5 years between children conceived after fertility treatment
or by subfertile parents compared with that of children born to fertile parents.
However, children born after fertility treatment may show catch-up growth during
childhood.
PMID- 25123637
TI - Outcomes of primary surgical evacuation during the first trimester in different
types of implantation in women with cesarean scar pregnancy.
AB - OBJECTIVE: To assess the efficacy and safety of primary surgical evacuation
therapy for cesarean scar pregnancy (CSP) of the first trimester, and to evaluate
its possible prognostic factors. DESIGN: Retrospective consecutive cohort study.
SETTING: Tertiary care university hospital. SUBJECT(S): A cohort of patients with
CSP and clear ultrasound images who underwent primary surgical evacuation from
January 2000 to December 2012. INTERVENTION(S): Patients fulfilling the
ultrasound criteria of CSP were further classified into superficial and deep
groups according to their implantation locations and extents. The final decision
on the method of treatment, including methotrexate chemotherapy, surgical
evacuation, and others, was made by the patients after consultation with the
physician. Pretreatment patient characteristics were compared in the patients
with superficial and deep implantation, as were the results after primary
surgical evacuation. MAIN OUTCOME MEASURE(S): Rates of successful treatment by
primary surgical evacuation of CSP and the need for salvage intervention in the
patients with deep and superficial implantation. RESULT(S): Forty-eight CSP
patients who had sufficient data and imaging for analysis were enrolled. Of these
48 cases, 26 in the superficial group and 14 in the deep group were willing to
undergo primary surgical evacuation. Blood loss and need for salvage intervention
were significantly lower in the patients with superficial implantation. Surgical
evacuation was successful in 23 of 26 patients (88.5%) with superficial
implantation and in 8 of 14 patients (57.1%) with deep implantation. Patients who
failed primary surgical evacuation showed complete recovery, with uterus
preservation, after salvage interventions, including laparoscopic surgery,
angioembolization, and laparotomy. CONCLUSION(S): Preoperative determination of
CSP implantation depth and extent is important in selecting candidates for
surgical treatment. Primary single-step surgical evacuation was successful in
most patients with superficial implantation, but patients should be informed of
the possibility of salvage interventions before undergoing surgical evacuation.
PMID- 25123638
TI - Preferences and needs regarding future contact with donation offspring among
identity-release gamete donors: results from the Swedish Study on Gamete
Donation.
AB - OBJECTIVE: To investigate the attitudes and preferences regarding future contact
with donation offspring among identity-release donors of oocytes or sperm.
DESIGN: Longitudinal cohort study. SETTING: University-based fertility clinics in
Sweden. PATIENT(S): A total of 210 women and men were questioned 5-8 years after
their donation of oocytes or sperm. INTERVENTION(S): Questionnaires given to
donors prior to their donation and 5-8 years after donation. MAIN OUTCOME
MEASURE(S): Donors' attitudes and preferences regarding future contact with their
donation offspring. RESULT(S): A majority of identity-release oocyte (65%) and
sperm (70%) donors were positive toward being contacted by an offspring of mature
age. More than half wanted to be notified by the clinic when an offspring
requested information about them, but about a third were negative toward
receiving this information. One in four reported a need for counseling regarding
future contact with an offspring. CONCLUSION(S): Several years after donation, a
majority of identity-release oocyte and sperm donors show positive attitudes
toward future contact with their offspring. Donors appear to have different
preferences for information and support regarding such contact. Fertility clinics
and health-care services should provide counseling regarding contact with an
offspring to the donors who express a need for this.
PMID- 25123639
TI - Increased risk of pregnancy-induced hypertension and operative delivery after
conception induced by in vitro fertilization/intracytoplasmic sperm injection in
women aged 40 years and older.
AB - OBJECTIVE: To clarify the association between preconception fertility status and
obstetric outcomes in women aged 40 years and older. DESIGN: Retrospective study
by reviewing medical records. SETTING: Tertiary perinatal center in a university
hospital. PATIENT(S): 330 women aged 40 years and older who delivered a singleton
from 2006 to 2010, and 450 women aged 30 to 34 years who delivered at the same
facility as controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Incidence
of pregnancy-induced hypertension, gestational diabetes mellitus, preterm birth,
low birth weight, and mode of delivery assessed based on the mode of conception;
spontaneous conception (SC) and in vitro fertilization/intracytoplasmic sperm
injection conception (IVF-ICSI). RESULT(S): The incidence of pregnancy-induced
hypertension was statistically significantly higher in IVF-ICSI group than the SC
group. This gap was commonly observed in both the women aged 40 years and older
and those in the 30 to 34 age group. No statistically significant difference was
observed in the frequency of gestational diabetes mellitus, preterm birth, or low
birth weight. As a characteristic of nulliparous women of advanced age, the rate
of operative delivery, which includes emergency cesarean section and instrumental
delivery, was statistically significantly higher in IVF-ICSI group than in the SC
group. Detailed investigation into the medical indications for operative delivery
revealed that the difference was attributable to the elevated incidence of labor
protraction and arrest. CONCLUSION(S): Preconception fertility status can be a
predicting factor of the incidence of pregnancy-induced hypertension and labor
outcome, especially for women aged 40 years and older.
PMID- 25123640
TI - Refined phenotyping, large cohorts, and collaborative research are vital for
realizing the potential of genomics to transform care for male infertility.
PMID- 25123641
TI - Resolvins RvD1 and 17(R)-RvD1 alleviate signs of inflammation in a rat model of
endometriosis.
AB - OBJECTIVE: To study the effects of two resolvins of D series, RvD1 and 17(R)
RvD1, on inflammatory signs associated with endometriosis (ENDO). DESIGN: In vivo
research study. SETTING: Research laboratory. ANIMAL(S): Female Sprague-Dawley
rats. INTERVENTION(S): Intravenous or intraperitoneal injections of RvD1 (300
ng/kg) or 17(R)-RvD1 (300 and 900 ng/kg) in rats with surgically induced ENDO.
MAIN OUTCOME MEASURE(S): Vascular permeability of ectopic endometrial growths was
assessed by Evans Blue extravasation; vaginal hyperalgesia was assessed with
telemetered visceromotor response. RESULT(S): Both resolvins, but not vehicle,
significantly decreased vascular permeability in ectopic endometrial tissue.
17(R)-RvD1 also significantly alleviated severity of vaginal hyperalgesia.
CONCLUSION(S): Our results suggest that RvD1 and 17(R)-RvD1 can be considered for
further investigation of their therapeutic potential for treating ENDO.
PMID- 25123643
TI - High-level expression in Escherichia coli, purification and kinetic
characterization of Plasmodium falciparum M1-aminopeptidase.
AB - Plasmodium falciparum neutral metallo-aminopeptidase (PfAM1), a member of the M1
family of metallo proteases, is a promising target for malaria, a devastating
human parasitic disease. We report the high-level expression of PfAM1 in
Escherichia coli BL21. An optimized gene, with a codon adaptation index and an
average G/C content higher than the native gene, was synthesized and cloned in
the pTrcHis2B vector. Optimal expression was achieved by induction with 1mM IPTG
at 37 degrees C for 18h. This allowed obtaining 100mg of recombinant PfAM1
(rPfAM1) per L of culture medium; 19% of the E. coli soluble protein mass was
from rPFAM1. rPfAM1, fused to an amino-terminal 6*His tag, was purified in a
single step by immobilized metal ion affinity chromatography. The protein showed
only limited signs of proteolytic degradation, and this step increased purity 27
fold. The kinetic characteristics of rPfAM1, such as a neutral optimal pH, a
preference for substrates with basic or hydrophobic amino acids at the P1
position, an inhibition profile typical of metallo-aminopeptidases, and
inhibition from Zn(2+) excess, were similar to those of the native PfAM1. We have
thus optimized an expression system that should be useful for identifying new
PfAM1 inhibitors.
PMID- 25123644
TI - Seizure recurrence following pyridoxine withdrawal in a patient with pyridoxine
dependent epilepsy.
AB - Pyridoxine-dependent epilepsy (PDE) is an autosomal recessive disorder
characterized by early onset and recurrent seizures that can be controlled by a
high dose of pyridoxine. PDE is caused by mutations in ALDH7A1, which encodes
antiquitin. Antiquitin converts alpha-aminoadipic semialdehyde to alpha
aminoadipic acid. Seizure recurrence after pyridoxine withdrawal is a criterion
for diagnosis, but PDE can be diagnosed conclusively by genetic testing for
mutations in the ALDH7A1 gene. In this case study, we report the long-term follow
up of a patient suspected with PDE. She experienced prolonged generalized tonic
seizures and was hospitalized in an intensive care unit following pyridoxine
withdrawal. Later, we identified a compound heterozygous mutation, c.1216G>A,
p.Gly406Arg, and a novel splice donor site mutation, IVS9+5G>A. Confirmation of
these mutations would have prevented an unsafe withdrawal test. This case
suggests the importance of the genetic determination of PDE to avoid the
diagnostic withdrawal of pyridoxine.
PMID- 25123642
TI - Efficient production and purification of recombinant human interleukin-12 (IL-12)
overexpressed in mammalian cells without affinity tag.
AB - Interleukin-12 is a heterodimeric, pro-inflammatory cytokine that is a key driver
of cell-mediated immunity. Clinical interest in IL-12 is significant due to its
potent anti-tumor activity and efficacy in controlling certain infectious
diseases such as Leishmaniasis and Listeria infection. For clinical applications,
the ease of production and purification of IL-12 and the associated cost
continues to be a consideration. In this context, we report a simple and
effective heparin-affinity based purification of recombinant human IL-12 (hIL-12)
from the serum-free supernatants of stable IL-12-transduced HEK293 cells.
Fractionation of culture supernatants on heparin Sepharose columns revealed that
hIL-12 elutes as a single peak in 500 mM NaCl. Coomassie staining and Western
blot analysis showed that hIL-12 eluted in 500 mM NaCl is homogeneous. Purity of
hIL-12 was ascertained by RP-HPLC and ESI-MS analysis, and found to be ~98%.
Western blot analysis, using monoclonal antibodies, demonstrated that the crucial
inter-subunit disulfide bond linking the p35 and p40 subunits is intact in the
purified hIL-12. Results of far UV circular dichroism, steady-state tryptophan
fluorescence, and differential scanning calorimetry experiments suggest that
purified hIL-12 is in its stable native conformation. Enzyme linked immunosorbent
assays (ELISAs) and bioactivity studies demonstrate that hIL-12 is obtained in
high yields (0.31+/-0.05 mg/mL of the culture medium) and is also fully
bioactive. Isothermal titration calorimetry data show that IL-12 exhibits a
moderate binding affinity (Kd(app)=69+/-1 MUM) to heparin. The purification
method described in this study is expected to provide greater impetus for
research on the role of heparin in the regulation of the function of IL-12. In
addition, the results of this study provide an avenue to obtain high amounts of
IL-12 required for structural studies which are aimed at the development of novel
IL-12-based therapeutics.
PMID- 25123645
TI - Chronic cannabinoid receptor stimulation selectively prevents motor impairments
in a mouse model of Huntington's disease.
AB - Huntington's disease (HD) is a devastating neurodegenerative disease
characterized by a progressive decline in motor abilities, as well as in
cognitive and social behaviors. Most of these behavioral deficits are
recapitulated in the R6/1 transgenic mouse, which can therefore be used as an
experimental model to identify the neurobiological substrates of HD pathology and
to design novel therapeutic approaches. The endocannabinoid system (ECS) is a
relevant candidate to participate in the etiopathology of HD as it is a key
modulator of brain function, especially in areas primarily affected by HD
dysfunction such as the striatum. Thus, some studies have demonstrated an
association between HD progression and alterations in the expression of several
ECS elements, thereby suggesting that improving ECS function may constitute a
useful strategy to eliminate or at least delay the appearance of HD symptoms.
Here this hypothesis was specifically tested by evaluating whether the
administration of a well-characterized cannabinoid receptor agonist (WIN 55,212),
either acutely or chronically, improves the HD-like symptoms in R6/1 mice. While
acute treatment did not change the behavioral phenotype of transgenic animals,
chronic administration was able to prevent the appearance of motor deficits, to
increase the number of striatal huntingtin inclusions and to prevent the loss of
striatal medium-sized spiny neurons, without affecting the social or cognitive
alterations. These findings suggest that prolonged administration of cannabinoid
receptor agonists could be an appropriate strategy for selectively improving
motor symptoms and stimulating neuroprotective processes in HD patients.
PMID- 25123646
TI - Inducing Muscle Heat Shock Protein 70 Improves Insulin Sensitivity and Muscular
Performance in Aged Mice.
AB - Heat shock proteins (HSPs) are molecular chaperones with roles in longevity and
muscular preservation. We aimed to show elevating HSP70 improves indices of
health span. Aged C57/BL6 mice acclimated to a western diet were randomized into:
geranylgeranylacetone (GGA)-treated (100 mg/kg/d), biweekly heat therapy (HT), or
control. The GGA and HT are well-known pharmacological and environmental inducers
of HSP70, respectively. Assessments before and after 8 weeks of treatment
included glycemic endpoints, body composition, and muscular endurance, power, and
perfusion. An HT mice had more than threefold, and GGA mice had a twofold greater
HSP70 compared with control. Despite comparable body compositions, both treatment
groups had significantly better insulin sensitivity and insulin signaling
capacity. Compared with baseline, HT mice ran 23% longer than at study start,
which was significantly more than GGA or control. Hanging ability (muscular
endurance) also tended to be best preserved in HT mice. Muscle power, contractile
force, capillary perfusion, and innervation were not different. Heat treatment
has a clear benefit on muscular endurance, whereas HT and GGA both improved
insulin sensitivity. Different effects may relate to muscle HSP70 levels. An HSP
induction could be a promising approach for improving health span in the aged
mice.
PMID- 25123648
TI - Delayed duodenal obstruction after intramural hematoma in a patient with
paroxysmal nocturnal hemoglobinuria: A case report.
AB - INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal stem cell
disorder of hematopoietic cells. Gastrointestinal complications of PNH are rare
and mostly related with intravascular thrombosis or intramural hematoma.
PRESENTATION OF CASE: We describe a case of a man with PNH complicated by
intramural duodenal hematoma initially treated with supportive care. Three months
after his first admission; he was admitted to the emergency department with
abdominal pain, nausea and vomiting. He had undergone to surgery because of
duodenal obstruction was treated with duodenojejunal by-pass surgery. DISCUSSION:
Patients were healed from gastrointestinal complications could suffer from
gastrointestinal strictures, which cause wide spread symptoms ranging from
chronic abdominal pain and anorexia to intestinal obstruction. CONCLUSION: We
report a rare intestinal obstruction case caused by stricture at the level of
ligamentum Treitz with PNH. The possibility simply has to be borne in mind that
strictures can be occurring at hematoma, ischemia or inflammation site of
gastrointestinal tract.
PMID- 25123649
TI - Malignant triton tumour of the sinonasal tract: Case report and literature
review.
AB - INTRODUCTION: The objective is to report a rare tumour of the sinonasal tract and
conduct a literature review. Malignant triton tumour is a subtype of malignant
schwannoma with rhabdomyoblastic differentiation. It is a very rare tumour, with
only 15 reported cases involving the sinonasal region. PRESENTATION OF CASE:
Forty-seven years old female presented with a right-sided epistaxis, progressive
right sided nasal obstruction and anosmia and a visible mass in the right nasal
cavity. Imaging studies showed a mass extending from the piriform aperture to the
nasopharynx in contact with the dura and the orbital content. The mass was
biopsied and the result was consistent with malignant triton tumour. The patient
refused the surgery at first so chemotherapy with MAID protocol was started.
After the fourth course of chemotherapy the treatment was stopped due to patient
intolerance and a thrombosis of the jugular vein. Patient then underwent surgery
with frontal craniotomy and dural excision, endoscopic control was done at the
end to insure a complete removal. The patient received Radiotherapy in the
postoperative period (56 Greys). At 5 years of follow up the patient is doing
fine with no signs of recurrence and normal ophthalmological findings.
DISCUSSION: Sixteen cases, including our case, have been reported to date in the
literature. The mean age at presentation is 61 years. None of cases were
associated with neurofibromatosis type 1. Eight patients were reported to be
alive 5 years post-treatment, and 2 patients were reported to have died of the
disease. The prognosis for triton tumours in the sinonasal tract is better than
that for triton tumours in other locations. CONCLUSION: Malignant triton tumour
is a rare malignancy of the sinonasal tract. Otolaryngologists should be aware of
this disease. The optimal treatment should include radical resection of the
tumour.
PMID- 25123647
TI - Circulating Proteomic Signatures of Chronological Age.
AB - To elucidate the proteomic features of aging in plasma, the subproteome targeted
by the SOMAscan assay was profiled in blood samples from 202 females from the
TwinsUK cohort. Findings were replicated in 677 independent individuals from the
AddNeuroMed, Alzheimer's Research UK, and Dementia Case Registry cohorts. Results
were further validated using RNAseq data from whole blood in TwinsUK and the most
significant proteins were tested for association with aging-related phenotypes
after adjustment for age. Eleven proteins were associated with chronological age
and were replicated at protein level in an independent population. These were
further investigated at gene expression level in 384 females from the TwinsUK
cohort. The two most strongly associated proteins were chordin-like protein 1
(meta-analysis beta [SE] = 0.013 [0.001], p = 3.66 * 10(-46)) and pleiotrophin
(0.012 [0.005], p = 3.88 * 10(-41)). Chordin-like protein 1 was also
significantly correlated with birthweight (0.06 [0.02], p = 0.005) and with the
individual Framingham 10-years cardiovascular risk scores in TwinsUK (0.71
[0.18], p = 9.9 * 10(-5)). Pleiotrophin is a secreted growth factor with a
plethora of functions in multiple tissues and known to be a marker for
cardiovascular risk and osteoporosis. Our study highlights the importance of
proteomics to identify some molecular mechanisms involved in human health and
aging.
PMID- 25123650
TI - An electronic environment and contact direction sensitive scoring function for
predicting affinities of protein-ligand complexes in Contour((r)).
AB - Contour((r)) is a computational structure-based drug design technology that grows
drug-like molecules by assembling context sensitive fragments in well-defined
binding pockets. The grown molecules are scored by a novel empirical scoring
function developed using high-resolution crystal structures of diverse classes of
protein-ligand complexes and associated experimental binding affinities. An
atomic model bearing features of the valence bond and VSEPR theories embodying
their molecular electronic environment has been developed for non-covalent
intermolecular interactions. On the basis of atomic hybridization and
polarization states, each atom is modeled by features representing electron lone
pairs, p-orbitals, and polar and non-polar hydrogens. A simple formal charge
model was used to differentiate between polar and non-polar atoms. The
interaction energy and the desolvation contribution of the protein-ligand
association energy is computed as a linear sum of pair-wise interactions and
desolvation terms. The pair-wise interaction energy captures short-range positive
electrostatic interactions via hydrogen bonds, electrostatic repulsion of like
charges, and non-bond contacts. The desolvation energy is estimated by
calculating the energy required to desolvate interaction surfaces of the protein
and the ligand in the complex. The scoring function predicts binding energies of
a diverse set of protein-ligand complexes used for training with a correlation
coefficient of 0.61. It also performs equally well in predicting association
energies of a diverse validation set of protein-ligand complexes with a
correlation coefficient of 0.57, which is equivalent to or better than 12 other
scoring functions tested against this set including X-Score, GOLD, and DrugScore.
PMID- 25123651
TI - Computational and statistical study on the molecular interaction between antigen
and antibody.
AB - Monoclonal antibodies are one of the most successful bio-molecules utilized in
the clinical scene of today. It is important to clarify general characteristics
of the interaction between antigen and antibody and to draw a guide for enhancing
their binding affinity in rational design of antibody drugs. In this study, we
carried out molecular dynamics simulations for 20 kinds of antigen-antibody
complexes. From the statistical analysis of the calculation results, the
following findings were deduced. At complementarity determining regions (CDRs) of
the antibodies, the rates for the presence of serine (Ser) and tyrosine (Tyr) are
high. The amino residues involved in direct hydrogen bonds between antigens and
antibodies were examined by counting the numbers of the hydrogen bonds from the
respective residues. The contribution of Tyr to the direct hydrogen bonding was
the highest and that of Ser was the fourth. Furthermore, the short-distance
hydrogen bonds, which is assumed to be so-called "low-barrier hydrogen bond",
were observed at CDRs in three complexes. Interestingly, Ser is involved in the
short-distance hydrogen bonding in two cases out of the three. This result
suggests that these two unchanged polar amino acid residues play an important
role for recognition of antigen. In almost all of the complexes (18/20), the
contribution of the electrostatic energy (DeltaEele) to the binding free energy
was calculated to be larger than that of the van der Waals energy (DeltaEvdw).
This dominance of the electrostatic energy is in contrast to the case that low
molecular-weight compounds are bound to their targets. The findings of this study
will be helpful to design an antibody with a high specificity and a high affinity
to the antigen.
PMID- 25123652
TI - Distortion from planarity in arenes produced by internal rotation of one single
hydroxyl hydrogen: the case of alternariol.
AB - Alternariol (AOH) and alternariol methyl ether (AME) are compounds toxic to farm
animals and humans produced by ubiquitous fungi of the Alternaria genus.
Information on chemical and physical properties of these compounds is rather
scarce although their X-ray structures are known. AOH and AME are composed of
three aromatic rings with three hydroxyl groups. However, the crystal structure
of AOH is nonplanar whereas that of AME which differs only in one methyl group
substituting one hydroxyl hydrogen is planar. By means of quantum calculations we
find that the internal rotation of that single hydrogen affects the structure of
AOH producing deviations from planarity near 5 degrees . We also show that
although quantum calculations predict energy differences about 5kcal/mol between
planar and perpendicular conformations of that hydrogen, its rotation has no
noticeable effects on electron density properties that could indicate
modifications of aromaticity features. Based upon these results, we suggest an
explanation to the nonplanarity of the AOH crystal solely in terms of the spatial
arrangement of molecules in the crystal interconnected through a network of
hydrogen bonds involving rotatable hydroxyl hydrogens that produce distortions
from planarity.
PMID- 25123653
TI - Evaluation of novel reactive MgO activated slag binder for the immobilisation of
lead and zinc.
AB - Although Portland cement is the most widely used binder in the
stabilisation/solidification (S/S) processes, slag-based binders have gained
significant attention recently due to their economic and environmental merits. In
the present study, a novel binder, reactive MgO activated slag, is compared with
hydrated lime activated slag in the immobilisation of lead and zinc. A series of
lead or zinc-doped pastes and mortars were prepared with metal to binder ratio
from 0.25% to 1%. The hydration products and microstructure were studied by X-ray
diffraction, thermogravimetric analysis and scanning electron microscopy. The
major hydration products were calcium silicate hydrate and hydrotalcite-like
phases. The unconfined compressive strength was measured up to 160 d. Findings
show that lead had a slight influence on the strength of MgO-slag paste while
zinc reduced the strength significantly as its concentration increased. Leachate
results using the TCLP tests revealed that the immobilisation degree was
dependent on the pH and reactive MgO activated slag showed an increased pH
buffering capacity, and thus improved the immobilisation efficiency compared to
lime activated slag. It was proposed that zinc was mainly immobilised within the
structure of the hydrotalcite-like phases or in the form of calcium zincate,
while lead was primarily precipitated as the hydroxide. It is concluded,
therefore, that reactive MgO activated slag can serve as clinker-free alternative
binder in the S/S process.
PMID- 25123654
TI - Adherence to diet and fluid restriction of individuals on hemodialysis treatment
and affecting factors in Turkey.
AB - AIM: This study was conducted to determine adherence to diet and fluid
restriction in hemodialysis-treated individuals and the affecting factors in
Turkey. METHODS: This descriptive study was conducted between 15 October 2010 and
15 January 2011 in subjects who voluntarily agreed to participate in the study
from three dialysis centers in a city located in the Central Anatolia Region of
Turkey. One hundred and twenty-one individuals treated with hemodialysis made up
the study sample. The data were collected using a questionnaire consisting of 41
questions and the Dialysis Diet and Fluid Non-adherence Questionnaire. The data
were evaluated with percentage, median, Mann-Whitney U-test, Kruskal-Wallis test,
Student's t-test in independent samples and Spearman's rank correlation
coefficient. RESULTS: The authors found that 98.3% of the individuals experienced
non-adherence to diet and 95.0% with fluid restriction. The authors found a weak
and negative relationship between calcium levels and non-adherence to fluid
restriction, a weak relationship between phosphorus levels and diet non-adherence
frequency and degree and the fluid non-adherence frequency scores, and a moderate
positive relationship between phosphorus levels and fluid restriction non
adherence degree scores (P < 0.05). CONCLUSION: Based on these results, regular
training and information regarding diet and fluid restriction must be provided to
individuals aged 21-35 years with no one in the family to help with their care,
those who consumed salted food, or had interdialytic weight gain of 4.5 kg or
more.
PMID- 25123655
TI - Role of somatic cancer mutations in human protein lysine methyltransferases.
AB - Methylation of lysine residues is an important post-translational modification of
histone and non-histone proteins, which is introduced by protein lysine
methyltransferases (PKMTs). An increasing number of reports demonstrate that
aberrant lysine methylation plays a central role in carcinogenesis that is often
correlated with abnormal expression of PKMTs. Recent whole genome and whole
transcriptome sequencing projects have also discovered several somatic mutations
in PKMTs that frequently appear in various tumors. These include chromosomal
translocations that lead to aberrant expression or mistargeting of PKMTs and
nonsense or frameshift mutations, which cause the loss of the protein function.
Another type of mutations are missense mutations which may lead to the loss of
enzyme activity, but may also alter the properties of PKMTs either by changing
the product or substrate specificity or by increasing the enzymatic activity
finally leading to a gain-of-function phenotype. In this review, we provide an
overview of the roles of EZH2, SETD2, NSD family, SMYD family, MLL family and
DOT1L PKMTs in cancer focusing on the effects of somatic cancer mutations in
these enzymes. Investigation of the effect of somatic cancer mutations in PKMTs
is pivotal to understand the general role of this important class of enzymes in
carcinogenesis and to improve and develop more individualized cancer therapies.
PMID- 25123656
TI - A validated score estimating ambulatory status following radiotherapy of elderly
patients for metastatic spinal cord compression.
AB - BACKGROUND: This study was performed to develop a validated score predicting
ambulatory status after radiotherapy (RT) alone for metastatic spinal cord
compression (MSCC) in elderly patients. METHODS: 1,129 elderly patients (>=65
years) were assigned to the test (N = 565) or validation group (N = 564). In the
test group, nine pre-treatment factors (age, gender, tumor type, number of
involved vertebrae, pre-RT ambulatory status, other bone metastases, visceral
metastases, interval cancer diagnosis to RT, time developing motor deficits) and
fractionation regimen were investigated. Factors significantly associated with
post-RT ambulatory status on multivariate analysis were included in the score.
The score for each factor was determined by dividing the post-RT ambulatory rate
at 1 month (%) by 10. The total score represented the sum of these scores.
RESULTS: In the multivariate analysis of the test group, age, primary tumor type,
pre-RT ambulatory status, visceral metastases, and time developing motor deficits
were significantly associated with post-RT ambulatory status. Total scores were
19 to 41 points. In the test group, post-RT ambulatory rates were 5% for 19-25
points, 35% for 26-30 points, 80% for 31-34 points, and 98% for 35-41 points (p <
0.001). 6-month survival rates were 11%, 21%, 59% and 76%, respectively. In the
validation group, post-RT ambulatory rates were 4%, 33%, 77% and 98%,
respectively (p < 0.001). CONCLUSIONS: Patients achieving 19-25 points had very
poor functional outcomes and survival, and may receive single-fraction RT for
pain relief. Selected patients with 26-34 points may benefit from additional
surgery. Patients achieving >=35 points achieved favorable results after RT
alone.
PMID- 25123658
TI - Randomness in highly reflective silver nanoparticles and their localized optical
fields.
AB - Reflection of near-infrared light is important for preventing heat transfer in
energy saving applications. A large-area, mass-producible reflector that contains
randomly distributed disk-shaped silver nanoparticles and that exhibits high
reflection at near-infrared wavelengths was demonstrated. Although resonant
coupling between incident light and the nanostructure of the reflector plays some
role, what is more important is the geometrical randomness of the nanoparticles,
which serves as the origin of a particle-dependent localization and hierarchical
distribution of optical near-fields in the vicinity of the nanostructure. Here we
show and clarified the unique optical near-field processes associated with the
randomness seen in experimentally fabricated silver nanostructures by adapting a
rigorous theory of optical near-fields based on an angular spectrum and detailed
electromagnetic calculations.
PMID- 25123657
TI - The role of ClpP, RpoS and CsrA in growth and filament formation of Salmonella
enterica serovar Typhimurium at low temperature.
AB - BACKGROUND: Salmonellae are food-borne pathogens of great health and economic
importance. To pose a threat to humans, Salmonellae normally have to cope with a
series of stressful conditions in the food chain, including low temperature. In
the current study, we evaluated the importance of the Clp proteolytic complex and
the carbon starvation protein, CsrA, for the ability of Salmonella Typhimurium to
grow at low temperature. RESULTS: A clpP mutant was severely affected in growth
and formed pin point colonies at 10 degrees C. Contrary to this, rpoS and
clpP/rpoS mutants were only slightly affected. The clpP mutant formed cold
resistant suppressor mutants at a frequency of 2.5 * 10(-3) and these were found
not to express RpoS. Together these results indicated that the impaired growth of
the clpP mutant was caused by high level of RpoS. Evaluation by microscopy of the
clpP mutant revealed that it formed filamentous cells when grown at 10 degrees C,
and this phenotype too, disappered when rpoS was mutated in parallel indicating a
RpoS-dependency. A csrA (sup) mutant was also growth attenuated a low
temperature. An rpoS/csrA (sup) double mutant was also growth attenuated,
indicating that the phenotype of the csrA mutant was independent from RpoS.
CONCLUSIONS: The cold sensitivity of clpP mutant was associated with increased
levels of RpoS and probably caused by toxic levels of RpoS. Although a csrA
mutant also accumulated high level of RpoS, growth impairment caused by lack of
csrA was not related to RpoS levels in a similar way.
PMID- 25123659
TI - A comprehensive survey of non-canonical splice sites in the human transcriptome.
AB - We uncovered the diversity of non-canonical splice sites at the human
transcriptome using deep transcriptome profiling. We mapped a total of 3.7
billion human RNA-seq reads and developed a set of stringent filters to avoid
false non-canonical splice site detections. We identified 184 splice sites with
non-canonical dinucleotides and U2/U12-like consensus sequences. We selected 10
of the herein identified U2/U12-like non-canonical splice site events and
successfully validated 9 of them via reverse transcriptase-polymerase chain
reaction and Sanger sequencing. Analyses of the 184 U2/U12-like non-canonical
splice sites indicate that 51% of them are not annotated in GENCODE. In addition,
28% of them are conserved in mouse and 76% are involved in alternative splicing
events, some of them with tissue-specific alternative splicing patterns.
Interestingly, our analysis identified some U2/U12-like non-canonical splice
sites that are converted into canonical splice sites by RNA A-to-I editing.
Moreover, the U2/U12-like non-canonical splice sites have a differential
distribution of splicing regulatory sequences, which may contribute to their
recognition and regulation. Our analysis provides a high-confidence group of
U2/U12-like non-canonical splice sites, which exhibit distinctive features among
the total human splice sites.
PMID- 25123660
TI - DEAD-box RNA helicase domains exhibit a continuum between complete functional
independence and high thermodynamic coupling in nucleotide and RNA duplex
recognition.
AB - DEAD-box helicases catalyze the non-processive unwinding of double-stranded RNA
(dsRNA) at the expense of adenosine triphosphate (ATP) hydrolysis. Nucleotide and
RNA binding and unwinding are mediated by the RecA domains of the helicase core,
but their cooperation in these processes remains poorly understood. We therefore
investigated dsRNA and nucleotide binding by the helicase cores and the isolated
N- and C-terminal RecA domains (RecA_N, RecA_C) of the DEAD-box proteins Hera and
YxiN by steady-state and time-resolved fluorescence methods. Both helicases bind
nucleotides predominantly via RecA_N, in agreement with previous studies on
Mss116, and with a universal, modular function of RecA_N in nucleotide
recognition. In contrast, dsRNA recognition is different: Hera interacts with
dsRNA in the absence of nucleotide, involving both RecA domains, whereas for YxiN
neither RecA_N nor RecA_C binds dsRNA, and the complete core only interacts with
dsRNA after nucleotide has been bound. DEAD-box proteins thus cover a continuum
from complete functional independence of their domains, exemplified by Mss116, to
various degrees of inter-domain cooperation in dsRNA binding. The different
degrees of domain communication and of thermodynamic linkage between dsRNA and
nucleotide binding have important implications on the mechanism of dsRNA
unwinding, and may help direct RNA helicases to their respective cellular
processes.
PMID- 25123661
TI - A high security double lock and key mechanism in HUH relaxases controls oriT
processing for plasmid conjugation.
AB - Relaxases act as DNA selection sieves in conjugative plasmid transfer. Most
plasmid relaxases belong to the HUH endonuclease family. TrwC, the relaxase of
plasmid R388, is the prototype of the HUH relaxase family, which also includes
TraI of plasmid F. In this article we demonstrate that TrwC processes its target
nic-site by means of a highly secure double lock and key mechanism. It is
controlled both by TrwC-DNA intermolecular interactions and by intramolecular DNA
interactions between several nic nucleotides. The sequence specificity map of the
interaction between TrwC and DNA was determined by systematic mutagenesis using
degenerate oligonucleotide libraries. The specificity map reveals the minimal nic
sequence requirements for R388-based conjugation. Some nic-site sequence variants
were still able to form the U-turn shape at the nic-site necessary for TrwC
processing, as observed by X-ray crystallography. Moreover, purified TrwC
relaxase effectively cleaved ssDNA as well as dsDNA substrates containing these
mutant sequences. Since TrwC is able to catalyze DNA integration in a nic-site
containing DNA molecule, characterization of nic-site functionally active
sequence variants should improve the search quality of potential target sequences
for relaxase-mediated integration in any target genome.
PMID- 25123662
TI - Effects of supercoiling on enhancer-promoter contacts.
AB - Using Brownian dynamics simulations, we investigate here one of possible roles of
supercoiling within topological domains constituting interphase chromosomes of
higher eukaryotes. We analysed how supercoiling affects the interaction between
enhancers and promoters that are located in the same or in neighbouring
topological domains. We show here that enhancer-promoter affinity and
supercoiling act synergistically in increasing the fraction of time during which
enhancer and promoter stay in contact. This stabilizing effect of supercoiling
only acts on enhancers and promoters located in the same topological domain. We
propose that the primary role of recently observed supercoiling of topological
domains in interphase chromosomes of higher eukaryotes is to assure that
enhancers contact almost exclusively their cognate promoters located in the same
topological domain and avoid contacts with very similar promoters but located in
neighbouring topological domains.
PMID- 25123663
TI - Why double-stranded RNA resists condensation.
AB - The addition of small amounts of multivalent cations to solutions containing
double-stranded DNA leads to inter-DNA attraction and eventual condensation.
Surprisingly, the condensation is suppressed in double-stranded RNA, which
carries the same negative charge as DNA, but assumes a different double helical
form. Here, we combine experiment and atomistic simulations to propose a
mechanism that explains the variations in condensation of short (25 base-pairs)
nucleic acid (NA) duplexes, from B-like form of homopolymeric DNA, to mixed
sequence DNA, to DNA:RNA hybrid, to A-like RNA. Circular dichroism measurements
suggest that duplex helical geometry is not the fundamental property that
ultimately determines the observed differences in condensation. Instead, these
differences are governed by the spatial variation of cobalt hexammine (CoHex)
binding to NA. There are two major NA-CoHex binding modes--internal and external-
distinguished by the proximity of bound CoHex to the helical axis. We find a
significant difference, up to 5-fold, in the fraction of ions bound to the
external surfaces of the different NA constructs studied. NA condensation
propensity is determined by the fraction of CoHex ions in the external binding
mode.
PMID- 25123664
TI - Structural basis of lariat RNA recognition by the intron debranching enzyme Dbr1.
AB - The enzymatic processing of cellular RNA molecules requires selective recognition
of unique chemical and topological features. The unusual 2',5'-phosphodiester
linkages in RNA lariats produced by the spliceosome must be hydrolyzed by the
intron debranching enzyme (Dbr1) before they can be metabolized or processed into
essential cellular factors, such as snoRNA and miRNA. Dbr1 is also involved in
the propagation of retrotransposons and retroviruses, although the precise role
played by the enzyme in these processes is poorly understood. Here, we report the
first structures of Dbr1 alone and in complex with several synthetic RNA
compounds that mimic the branchpoint in lariat RNA. The structures, together with
functional data on Dbr1 variants, reveal the molecular basis for 2',5'
phosphodiester recognition and explain why the enzyme lacks activity toward 3',5'
phosphodiester linkages. The findings illuminate structure/function relationships
in a unique enzyme that is central to eukaryotic RNA metabolism and set the stage
for the rational design of inhibitors that may represent novel therapeutic agents
to treat retroviral infections and neurodegenerative disease.
PMID- 25123665
TI - 7SL RNA represses p53 translation by competing with HuR.
AB - Noncoding RNAs (ncRNAs) and RNA-binding proteins are potent post-transcriptional
regulators of gene expression. The ncRNA 7SL is upregulated in cancer cells, but
its impact upon the phenotype of cancer cells is unknown. Here, we present
evidence that 7SL forms a partial hybrid with the 3'-untranslated region (UTR) of
TP53 mRNA, which encodes the tumor suppressor p53. The interaction of 7SL with
TP53 mRNA reduced p53 translation, as determined by analyzing p53 expression
levels, nascent p53 translation and TP53 mRNA association with polysomes.
Silencing 7SL led to increased binding of HuR to TP53 mRNA, an interaction that
led to the promotion of p53 translation and increased p53 abundance. We propose
that the competition between 7SL and HuR for binding to TP53 3'UTR contributes to
determining the magnitude of p53 translation, in turn affecting p53 levels and
the growth-suppressive function of p53. Our findings suggest that targeting 7SL
may be effective in the treatment of cancers with reduced p53 levels.
PMID- 25123670
TI - The shell game: how institutional review boards shuffle words.
AB - Concepts like coercion, vulnerability, and dignitary harm have acquired
specialized meanings in the research ethics literature. Institutional Review
Boards (IRBs), also called Research Ethics Committees (RECs), sometimes use these
concepts in two different ways without acknowledging or even realizing what they
are doing. IRBs mislabel any language that encourages subject participation in
trials as "coercive," then demand its removal as if it were actually coercive in
the sense of a threat of force. An example of language that is treated as
coercive is the use of the word "hope" in an educational brochure about clinical
trials. The concepts of vulnerability and dignitary harm are similarly misused.
The regulations instruct IRBs to protect vulnerable groups; but IRBs sometimes
use a group's vulnerability to one threat to protect it against an unrelated and
harmless threat, as when homeless people, who are vulnerable to street crime and
disease, are protected from the risk of an interview. Finally, the term
"dignitary harm" is so vague that IRBs can use it to restrict research that is
entirely free of risk, while ignoring the possibility that research might provide
the dignitary benefit of contributing to society's health and welfare. Dignitary
harm--usually nonphysical "harm" of which the subject is entirely unaware--can be
deemed more important than obtaining information that subjects want or actual
risk of physical injury. These vague or shifting definitions permit the IRB to
play a shell game without either the board or the investigator realizing what is
happening.
PMID- 25123671
TI - Anatomy of a transformation: a systematic effort to reduce mechanical restraints
at a state psychiatric hospital.
AB - OBJECTIVE: The authors describe efforts to reduce use of mechanical restraints at
a state psychiatric hospital. METHODS: Data were collected for individuals
admitted to the acute adult unit (AAU) (N=2,910) and the community transition
unit (CTU) (N=334) over three years. Two strategies aimed to reduce mechanical
restraint use. First, staff were trained in deescalation techniques, and a
response team was formed for crisis situations. Second, a policy change required
prior approval for use of mechanical restraint. RESULTS: Mechanical restraint was
significantly reduced on both units after the first strategy. After the second,
additional reduction was noted on AAU (98% total reduction) but not on CTU, where
the practice had already been eliminated. No increase in assaults or injuries was
noted. CONCLUSIONS: Reduction in mechanical restraint use is possible through
deescalation skills training, use of a response team, and policy changes. Strong
leadership, staff buy-in, provision of feedback, and quality monitoring were also
instrumental.
PMID- 25123669
TI - Bicarbonate transport inhibitor SITS modulates pH homeostasis triggering
apoptosis of Dalton's lymphoma: implication of novel molecular mechanisms.
AB - Bicarbonate transporter (BCT) plays a crucial role in maintaining pH homeostasis
of tumor cells by import of HCO3(-). This helps the tumor cells in manifesting
extracellular tumor acidosis, accompanied by a relative intracellular
alkalinization, which in turn promotes tumor progression. Therefore, blocking BCT
mediated HCO3(-) transport is envisaged as a promising anticancer therapeutic
approach. Thus, using a murine model of a T cell lymphoma, designated as Dalton's
lymphoma (DL), in the present in vitro investigation the antitumor consequences
of blocking BCT function by its inhibitor 4-acetamido-4-isothiocyanostilbene-2,2
disulfonate (SITS) were explored. Treatment of DL cells with SITS resulted in an
increase in the extracellular pH, associated with a decline in DL cell survival
and augmented induction of apoptosis. BCT inhibition also elevated the expression
of cytochrome c, caspase-9, caspase-3, Bax, reactive oxygen species, and nitric
oxide along with inhibition of HSP-70 and Bcl2, which regulate tumor cell
survival and apoptosis. SITS-treated DL cells displayed upregulated production of
IFN-gamma and IL-6 along with a decline of IL-10. Treatment of DL cells with SITS
also inhibited the expression of fatty acid synthase, which is crucial for
membrane biogenesis in neoplastic cells. The expression of lactate transporter
MCT-1 and multidrug resistance regulating protein MRP-1 got inhibited along with
hampered uptake of glucose and lactate production in SITS-treated DL cells. Thus,
the declined tumor cell survival following inhibition of BCT could be the
consequence of interplay of several inter-connected regulatory molecular events.
The outcome of this study indicates the potential of BCT inhibition as a novel
therapeutic approach for treatment of hematological malignancies.
PMID- 25123673
TI - Similar radiopathological features, but different postoperative recurrence rates,
between Stage I lung cancers arising in emphysematous lungs and those arising in
nonemphysematous lungs.
AB - OBJECTIVES: The aim of the present study was to clarify the differences between
lung cancer arising in emphysematous lungs and that arising in nonemphysematous
lungs with regard to radiopathological features and the postoperative recurrence
rate. METHODS: We retrospectively reviewed a prospective database of 212 patients
who underwent major lung resection for clinically diagnosed Stage I primary lung
cancer. Emphysematous lungs were identified on the basis of quantitative computed
tomography (CT). The biological features of the primary tumour were diagnosed
according to the presence or absence of a ground-glass component on high
resolution CT and the maximum standardized uptake value in [(18)F]
fluorodeoxyglucose positron emission tomography, in addition to conventional
characteristic factors. RESULTS: The risk factors for postoperative recurrence
were underlying emphysema, a high maximum standardized uptake value, the absence
of a ground-glass component, the pathological grade and lymph node metastasis,
whereas the risk factors for lymph node metastasis were a high maximum
standardized uptake value, the absence of a ground-glass component and the
pathological grade. Surprisingly, these risk factors were entirely matched
between patients with and without emphysematous lungs, regardless of the fact
that patients with emphysematous lungs had a higher recurrence rate. CONCLUSIONS:
Similar clinicopathological features, but different postoperative recurrence
rates, were found between Stage I lung cancers arising in emphysematous lungs and
those arising in nonemphysematous lungs. It may be valuable to search for
underlying molecular mechanisms that promote metastasis from primary tumours
arising in emphysema, such as paracrine effects between the tumour and pulmonary
emphysema.
PMID- 25123672
TI - Unilateral pulmonary oedema after minimally invasive cardiac surgery via right
anterolateral minithoracotomy.
AB - OBJECTIVES: To investigate the incidence of unilateral pulmonary oedema after
minimally invasive cardiac surgery (MICS) requiring unilateral lung collapse has
been unknown until now. METHODS: We analysed the data of 484 consecutive patients
undergoing minimally invasive cardiac surgery with unilateral lung collapse
between January 2008 and December 2013. The clinical regimen was changed in 2010
to a single dose of dexamethasone (approximately 1 mg/kg body weight)
administered after anaesthesia induction. RESULTS: Thirty-eight patients
developed a radiographically evident unilateral pulmonary oedema within 24 h
after surgery. Dexamethasone significantly reduced the incidence of this event
[4.0 vs 12.9%; unadjusted odds ratio (OR) 0.28, 95% confidence interval (CI) 0.14
0.58, P < 0.001]. One patient with and six patients without dexamethasone were
clinically symptomatic (P = 0.001). Logistic regression analysis identified four
variables significantly associated with the development of a unilateral lung
oedema: dexamethasone (OR 0.28, 95% CI 0.13-0.58, P = 0.001), diabetes mellitus
(OR 3.17, 95% CI 1.04-9.63, P = 0.04), the level of mean pulmonary arterial
pressure (OR 1.05 per mmHg, 95% CI 1.004-1.09, P = 0.03) and transfusion of fresh
frozen plasma (OR 2.31, 95% CI 1.02-5.25, P = 0.045). CONCLUSIONS: Our data
revealed a 7.9% incidence of radiographically evident unilateral pulmonary oedema
after MICS with intraoperative collapse of a lung. Of the total number of
patients, 1.5% simultaneously developed clinical symptoms. The influence of
corticosteroids, as well as the contribution of possible risk factors, needs
further evaluation.
PMID- 25123674
TI - Comparison of the early haemodynamics of stented pericardial and porcine aortic
valves.
AB - Data comparing the haemodynamic performance of stented pericardial and porcine
aortic valves are conflicting. Hence, we performed a systematic review and meta
analysis comparing the early haemodynamic parameters of stented pericardial and
porcine valves in patients undergoing isolated aortic valve replacement. Medline,
EMBASE and Web of Science were queried for English language original publications
from 2000 to 2013. Studies comparing porcine (PoV) and pericardial (PeV) with
regard to their haemodynamic parameters were included in this review. Continuous
data were pooled using the mean difference (MD) or the standardized mean
difference (SMD). A random-effect inverse weighted analysis was conducted; a P
value<0.05 is considered statistically significant. Results are presented with
95% confidence intervals. Thirteen studies (1265 PeV patients and 871 PoV
patients) were included in this analysis. The pooled transvalvular mean gradient
was lower for PeV [MD -4.6 (-6.45 to -2.77) mmHg; P<0.01]. Limiting this analysis
to small valves (19 and 21 mm; eight studies; 714 patients) revealed that the PeV
gradients were significantly lower [MD -4.5 (-5.7 to -3.2); P=0.001]. The
corresponding effective orifice area of PeV was significantly larger than PoV
[SMD 0.42 (0.15-0.69); P<0.01]. A sensitivity analysis comprising only randomized
controlled trials did not significantly alter results. When compared with porcine
valves, stented pericardial aortic valves have lower mean transvalvular gradients
early after implant. Even pericardial valves in smaller sizes (19 and 21 mm) have
a better haemodynamic profile when compared with their counterparts.
PMID- 25123675
TI - Muscle metabolism during tibial lengthening with regular and high distraction
rates.
AB - INTRODUCTION: Muscle regeneration is promoted when the Ilizarov method is used
for limb lengthening and deformity correction, but the regenerative ability of
muscles decreases when achieving large amounts of elongation. Much research has
been dedicated to studying the capabilities of muscles under lengthening, but no
reports are available that investigate the muscle metabolism. We supposed that
energy turnover would be activated in skeletal muscles under lengthening as a
response to distraction, and the activity of the energy turnover would grow in
proportion to the increase in the distraction rate or amount. MATERIALS AND
METHODS: We compared the metabolism of canine anterior tibial muscles (ATMs) by
regular and 3-mm high-frequency bone distraction in 30 dogs to obtain 14.5 +/-
0.8% lengthening from the initial tibial length. Group 1 (n = 12) had manual
lengthening with a rate of 1 mm per day. Three millimeters per day was produced
with 120 increments in automated mode in group 2 (n = 12). An intact group (n =
6) served as controls. ATMs were harvested at the end of distraction, after 30
days of fixation, and 30 days after frame removal. We assessed the activity of
lactate dehydrogenase, creatine phosphokinase, glucoso-6-phosphate dehydrogenase,
and catalase and calculated the concentration of malone dialdehyde, sarcoplasmic
and contractile proteins in the ATM extract. RESULTS: Energy turnover reactions
were activated in the ATM as a response to distraction forces, but the activity
of the energy turnover did not grow proportionally to the increased distraction
rate. Levels of sarcoplasmic and contractile proteins in the ATM decreased
insignificantly in both groups. CONCLUSIONS: High-frequency 3-mm daily
lengthening results in compensatory energy turnover changes in the muscle,
sufficient for prevention of catabolic processes.
PMID- 25123676
TI - Population-based study of the relationship between medial meniscus radial
displacement, determined by use of ultrasound screening, and knee pain.
AB - PURPOSE: The purpose of this population-based study was to clarify the incidence
of knee pain by use of ultrasound (US). METHODS: Medical check-ups were conducted
for residents of a mountain village in Japan. The subjects were 149 males and 252
females (802 knees) with a mean age of 63.5 +/- 12.5 years. US was used to
evaluate the medial joint space of both knees, with and without weight-bearing.
For each patient, medial radial displacement of the medial meniscus (MRD) and
number of osteophytes were evaluated. A questionnaire was used to determine
whether the subjects were currently experiencing knee pain while walking,
climbing stairs, or resting that had lasted more than one month. A visual analog
scale was used to assess knee pain. The subjects were divided into two groups,
those with knee pain (P group) and those without knee pain (non-P group), on the
basis of whether a visual analog scale (VAS) was less than or more than 20 mm
during walking, climbing stairs, or resting. Logistic regression analysis was
used to identify the factors associated with knee pain. RESULTS: Significantly
different weight-bearing MRD (WMRD), osteophytes, and pain while walking,
climbing stairs, or resting (p < 0.01) were found between the two groups.
Logistic regression analysis showed that WMRD was significantly associated with
knee pain during walking or while climbing stairs. CONCLUSION: We found that WMRD
was significantly associated with knee pain while walking or climbing stairs,
which are weight-bearing activities. On the basis of the findings of this study,
we believe US is a useful tool for evaluating the factors associated with knee
pain in a population-based study. LEVEL OF EVIDENCE: Level III.
PMID- 25123677
TI - [Exophthalmus with enlarged epibulbar vessels].
PMID- 25123678
TI - Prebiotic potential of Jerusalem artichoke (Helianthus tuberosus L.) in Wistar
rats: effects of levels of supplementation on hindgut fermentation, intestinal
morphology, blood metabolites and immune response.
AB - BACKGROUND: Many studies have been conducted using purified prebiotics such as
inulin or fructooligosaccharides (FOS) as nutraceuticals, but there is very
little information available on the prebiotic potential of raw products rich in
inulin and FOS, such as Jerusalem artichoke (JA; Helianthus tuberosus L.). The
present experiment aimed to evaluate the prebiotic effects of JA tubers in rats.
RESULTS: Seventy-two Wistar weanling rats divided into four groups were fed for
12 weeks on a basal diet fortified with pulverized JA tubers at 0 (control), 20,
40 and 60 g kg(-1) levels. Enhanced cell-mediated immunity in terms of skin
indurations (P = 0.082) and CD4+ T-lymphocyte population (P = 0.002) was observed
in the JA-supplemented groups compared with the control group. Blood haemoglobin
(P = 0.017), glucose (P = 0.001), urea (P = 0.004) and calcium (P = 0.048) varied
favourably upon inclusion of JA. An increasing trend (P = 0.059) in the length of
large intestine was apparent in the JA-fed groups. The tissue mass of caecum (P =
0.069) and colon (P = 0.003) was increased in the JA-supplemented groups,
accompanied by higher (P = 0.007) caecal crypt depth. The pH and ammonia
concentrations of intestinal digesta decreased and those of lactate and total
volatile fatty acids increased in the JA-fed groups. CONCLUSION: The results
suggest that JA had beneficial effects on immunity, blood metabolites, intestinal
morphometry and hindgut fermentation of rats.
PMID- 25123679
TI - Liquid biopsy in gastrointestinal stromal tumors: a novel approach.
AB - The role of molecular analysis in the management of gastrointestinal stromal
tumors (GIST) remains indisputable. To date, tumor tissue extracted from
specimens obtained by surgical or biopsy procedures has been the only source of
the tumor DNA required for the molecular and genomic assessment of cancer.
However, tumor tissue sampling has several clinical limitations: for example, the
invasiveness of these procedures precludes repeated sampling. Thus, it is
possible to obtain only a static molecular picture of the disease, a picture that
lacks the inter- and intra-metastatic molecular heterogeneity that characterizes
most GIST. In contrast, circulating tumor DNA obtained from a patient's
bloodstream, known as liquid biopsy, can theoretically overcome the limitations
of tissue biopsies and provide the same molecular and genomic information. GIST
are recognized as a paradigm of molecular biology among solid tumors. Although
few but promising data on liquid biopsy in GIST have been accumulated to date,
these tumors may provide the optimal field for application of this challenging
approach.
PMID- 25123681
TI - Epidemiological characteristics and immune status of children with Respiratory
Syncytial Virus.
AB - Respiratory Syncytial Virus (RSV) infections are the dominant cause of pneumonia
in children. In order to determine the epidemiological characteristics and immune
status of children with Respiratory Syncytial Virus, a prospective study was
performed among patients with RSV infection. Comparisons between RSV pneumonia
group and normal control group, RSV pneumonia group had lower IL-2 (median
levels, pg/ml: 3.8 vs. 5.1, P < 0.01), and higher IL-4 (median levels, pg/ml: 3.2
vs. 2.4, P < 0.01), IL-10 (median levels, pg/ml: 12.2 vs. 2.3, P < 0.01), and IFN
gamma (median levels, pg/ml: 13.4 vs. 4.6, P < 0.01). The level of IgE among
pneumonia patients caused by RSV increased sharply (median levels, mg/L: 48.1 vs.
8.8, P < 0.01). Another amazing finding is that after birth, the degree of IgE of
the children infected by RSV increases gradually with age. This effect is at its
peak in 0.6 years old. The IgE and eosinophil levels were higher when patients
suffered from RSV pneumonia with wheeze (IgE median levels, IU/ml: with wheeze:
72.74 vs. without wheeze: 11.5, P < 0.05; eosinophil median levels, *10(9) /l:
with wheeze: 0.21 vs. without wheeze: 0.05, P < 0.05). The main morbidity crowd
is the children under the age of 1 year old. The downregulation of IL2 and the
upregulation of IL-4, IL-10, IFN-gamma, and IgE happen after RSV infection.
PMID- 25123680
TI - The prevalence of general and abdominal obesity according to sasang constitution
in Korea.
AB - BACKGROUND: Obesity is an important risk factor for cardiovascular and metabolic
diseases and could affect mortality rates. Body mass index (BMI) and waist
circumference (WC) have been used to classify obesity, and waist-to-hip ratio
(WHR) has recently emerged as a discriminator of cardiovascular disease. Sasang
constitution (SC) is a kind of well-known traditional Korean medicine: Tae-eumin
(TE), Soeumin (SE), Taeyangin (TY) and Soyangin (SY) carrying a different level
of susceptibility to chronic diseases. We aimed to examine the prevalence in
general and abdominal obesity (AO) using BMI, WC and WHR according to SC in the
Korean population. METHODS: A total of 3,348 subjects were recruited from 24
Korean medicine clinics. Obesity was divided into three categories: general
obesity by BMI, abdominal obesity by waist circumference (WC AO) and abdominal
obesity by waist-to-hip ratio (WHR AO). A Chi-square test was performed to
compare prevalence, and logistic regression was conducted to generate odds ratios
(ORs) according to SC (p < .05). RESULTS: The prevalence of general obesity was
significantly higher in males than in females. The highest prevalence of general
obesity, WC AO and WHR AO were all observed in the TE type, and the SY and SE
types were followed in order, for both males and females respectively.The TE type
was highly associated with increased risk of general obesity (OR = 20.2, 95% CI:
12.4-32.9 in males and OR = 14.3, 95% CI: 10.1-20.2 in females), of WC AO (OR =
10.7, 95% CI: 7.2-15.9 in males and OR = 7.5, 95% CI: 5.8-9.6 in females), and of
WHR AO (OR = 4.6, 95% CI: 3.3-6.4 in males and OR = 3.8, 95% CI: 2.9-4.9 in
females) compared with the SE type. In addition, after controlling for age,
social status and eating habits, the ORs were similar to the crude model
according to gender and SC. CONCLUSIONS: This study shows that the prevalence of
obesity varies according to SC in the Korean population. In particular, the TE
type was highly associated with increased ORs for general obesity, WC AO and WHR
AO in both genders.
PMID- 25123682
TI - Influence of body mass index on skin grafting in pediatric burns.
AB - BACKGROUND: There is heterogeneous literature on the association of obese and
underweight body habitus on burn outcomes in adult and pediatric literature. We
examine the effect of standardized pediatric body mass index (BMI) categories
skin graft utilisation. METHODS: A retrospective chart review was performed on
children who underwent burn treatment from January 1995 to November 2011. BMI was
categorized by standard definitions: underweight (<5%), normal (5-85%),
overweight (85-95%), obese (>95%). RESULTS: There were 1164 patients: 77
underweight, 604 normal, 215 overweight, and 268 obese patients. No differences
existed between group demographics. Grafts were performed in 39% of underweight,
27% of normal, 22% of overweight, and 27% of obese patients. Underweight children
had nearly a 2 fold increase in their risk of full thickness burns and were 1.8
times more likely to undergo skin grafting than normal BMI children. Overweight
children had a significant decrease in the incidence skin grafting by 23% then
compared to normal weight children. There were no differences in percent TBSA
burned or percent TBSA grafted using ANOVA. CONCLUSIONS: Underweight pediatric
burn victims have an increased risk for skin grafting while mildly overweight
children are slightly protected from skin grafting.
PMID- 25123683
TI - Antigenic properties of N protein of hantavirus.
AB - Hantavirus causes two important rodent-borne viral zoonoses, hemorrhagic fever
with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome (HPS) in
North and South America. Twenty-four species that represent sero- and genotypes
have been registered within the genus Hantavirus by the International Committee
on Taxonomy of Viruses (ICTV). Among the viral proteins, nucleocapsid (N) protein
possesses an immunodominant antigen. The antigenicitiy of N protein is conserved
compared with that of envelope glycoproteins. Therefore, N protein has been used
for serological diagnoses and seroepidemiological studies. An understanding of
the antigenic properties of N protein is important for the interpretation of
results from serological tests using N antigen. N protein consists of about 430
amino acids and possesses various epitopes. The N-terminal quarter of N protein
bears linear and immunodominant epitopes. However, a serotype-specific and
multimerization-dependent antigenic site was found in the C-terminal half of N
protein. In this paper, the structure, function, and antigenicity of N protein
are reviewed.
PMID- 25123685
TI - Training endosonographers in cytopathology: improving the results of EUS-guided
FNA.
AB - BACKGROUND: Although on-site cytopathology services have a significant impact on
efficiency and accuracy of EUS-guided FNA (EUS-FNA), the availability of this
service is variable. OBJECTIVE: To evaluate the impact of an intensive 2-day
training program to educate endosonographers in EUS-related cytopathology.
DESIGN: Pilot study. SETTING: Tertiary care medical center. SUBJECTS: Six
endosonographers (5 male, median age, 35 years) with minimal previous
cytopathology exposure comprised the study cohort. METHODS: Pre- and posttraining
testing was administered. Training commenced with a cytopathology tutorial
focusing on 4 performance measures: specimen adequacy, sample interpretation,
specimen processing, and preliminary diagnosis. Eight live EUS-FNA cases were
then performed, and study participants independently completed 4 questions based
on performance measures for each case. The ability to independently smear and
stain slides and operate a microscope was additionally assessed after a hands-on
tutorial. MAIN OUTCOME MEASUREMENTS: Comparison of pretraining and posttraining
scores, improvement in performance measures for live cases, and ability to
independently handle specimens and operate a microscope. RESULTS: Compared with
pretraining, mean posttraining test scores improved by 63% from 48 to 78 out of
100. Mean live case performance score was 95%. Performances improved from 89% on
day 1 to 100% on day 2. After training, all endosonographers could independently
smear/stain slides and operate a microscope. LIMITATIONS: Long-term impact is
unclear. CONCLUSIONS: An intensive 2-day program was effective in training
endosonographers in the basics of EUS-related cytopathology. Incorporating basic
cytopathology in EUS fellowship curriculum will likely improve diagnostic
performance of tissue acquisition procedures.
PMID- 25123686
TI - Neuroaxonal dystrophy in Merino-Border Leicester * Polled Dorset lambs.
AB - CASE REPORT: The clinicopathological features of neuroaxonal dystrophy (NAD) in 2
lambs are described. Of 40 Merino-Border Leicester * Polled Dorset lambs on a
property in north-eastern Victoria, 4 presented with marked ataxia and
listlessness, and 2 affected animals (2 days and 2 weeks of age, respectively) of
both sexes were necropsied. Numerous axonal swellings (spheroids) were found in
the central nervous system, particularly in brainstem nuclei and spinal cord grey
matter, and there was severe spinal cord demyelination. CONCLUSIONS: This is the
first report of NAD in such crossbred lambs; the affected animals were much
younger than in previously described cases of ovine NAD and myelin loss was of
much greater magnitude than previously reported.
PMID- 25123687
TI - Isolation, identification and characterization of potential impurities in
cabazitaxel and their formation.
PMID- 25123684
TI - European bats as carriers of viruses with zoonotic potential.
AB - Bats are being increasingly recognized as reservoir hosts of highly pathogenic
and zoonotic emerging viruses (Marburg virus, Nipah virus, Hendra virus, Rabies
virus, and coronaviruses). While numerous studies have focused on the mentioned
highly human-pathogenic bat viruses in tropical regions, little is known on
similar human-pathogenic viruses that may be present in European bats. Although
novel viruses are being detected, their zoonotic potential remains unclear unless
further studies are conducted. At present, it is assumed that the risk posed by
bats to the general public is rather low. In this review, selected viruses
detected and isolated in Europe are discussed from our point of view in regard to
their human-pathogenic potential. All European bat species and their roosts are
legally protected and some European species are even endangered. Nevertheless,
the increasing public fear of bats and their viruses is an obstacle to their
protection. Educating the public regarding bat lyssaviruses might result in
reduced threats to both the public and the bats.
PMID- 25123689
TI - Mobility Limitation and Changes in Personal Goals Among Older Women.
AB - OBJECTIVES: Several theoretical viewpoints suggest that older adults need to
modify their personal goals in the face of functional decline. The aim of this
study was to investigate longitudinally the association of mobility limitation
with changes in personal goals among older women. METHOD: Eight-year follow-up of
205 women aged 66-78 years at baseline. RESULTS: Health-related goals were the
most common at both measurements. Goals related to independent living almost
doubled and goals related to exercise and to cultural activities substantially
decreased during the follow-up. Higher age decreased the likelihood for engaging
in new goals related to cultural activities and disengaging from goals related to
independent living. Women who had developed mobility limitation during the follow
up were less likely to engage in new goals related to exercise and more likely to
disengage from goals related to cultural activities and to health and
functioning. DISCUSSION: The results of this study support theories suggesting
that age-related losses such as mobility limitation may result in older adults
modifying or disengaging from personal goals.
PMID- 25123688
TI - Age, Rumination, and Emotional Recovery From a Psychosocial Stressor.
AB - OBJECTIVES: Exposure to psychosocial stressors often elicits increases in
negative affect and blood pressure (BP). Rumination, or thinking about a stressor
after it passes, is associated with delayed recovery. Given that older age is
associated with greater BP reactivity to psychosocial stressors, rumination may
be more detrimental to the recovery of older adults than younger adults. The
current study examined this question. We hypothesized that prolonged distress
resulting from rumination has greater effects on the recovery of older than
younger adults. METHOD: Fifty-two older (M = 69 years) and 61 younger (M = 21
years) adults were exposed to a lab stressor. Afterwards, participants were
randomly assigned to a rumination condition (n = 58) or a no-instruction control
condition (n = 55). RESULTS: Older participants in the rumination condition had
delayed BP recovery relative to those in the control condition and all younger
adults. Rumination did not influence affective recovery among any of the groups.
DISCUSSION: Rumination delays BP recovery among older adults, suggesting age
specific risks associated with different types of emotion regulation strategies.
PMID- 25123690
TI - Relationship quality and shared activity in marital and cohabiting dyads in the
National Social Life, Health, and Aging Project, Wave 2.
AB - OBJECTIVES: This paper introduces scales on shared activity and relationship
quality for married and partnered older adults using multiple indicators from the
second wave of National Social Life, Health, and Aging Project. METHOD: We
assessed the reliability of the scales using Cronbach's alpha and the item-total
correlation. We conducted exploratory factor analysis to explore the structure of
the items and compared the distribution of each scale means by age group and
gender. RESULTS: We found that the relational quality scale has a 2-factor
structure, including a positive and negative dimension. The shared activity scale
has a 1-factor structure. We found that partnered men show both higher positive
and higher negative relationship quality than do partnered women, suggesting that
more older men than women experience ambivalent feelings toward their spouse or
partner and more women than men have relationships of indifferent quality, with
relatively low costs and relatively low benefits. DISCUSSION: The separate
conceptualization of shared activity and relationship quality provides one way to
examine the dynamic nature of marital quality in later life such as the extent to
which shared activities among couples promote or detract from relationships'
quality. Analyses for individuals and for dyads are discussed.
PMID- 25123691
TI - Australian Idiopathic Pulmonary Fibrosis Registry: vital lessons from a national
prospective collaborative project.
AB - There is little Australian epidemiologic data on idiopathic pulmonary fibrosis
(IPF), a relatively uncommon but devastating disease. The vast geographic
distances in Australia have been a major impediment for collaborative research
into IPF. A collaborative national effort, the Australian IPF Registry, has been
formed, launched and is recruiting successfully (n = 359, January 2014). Our
experience provides unique insights for others wishing to set up IPF registries
and in time for a global IPF registry.
PMID- 25123692
TI - A comprehensive description of postpartum pain after cesarean delivery.
AB - OBJECTIVE: To describe women's experiences with the perception of, evaluation of,
and response to postpartum pain after cesarean delivery through the sensory,
affective, cognitive, and behavioral dimensions of pain. The secondary aim of
this research was to differentiate pain described with nociceptive and
neuropathic pain descriptors. DESIGN: Longitudinal, concurrent mixed methods
design. SETTING: Large, university-based, midwestern medical center.
PARTICIPANTS: Convenience sample of 30 low-risk women scheduled for cesarean
deliveries. METHODS: The PAINReportIt, a computerized version of the McGill Pain
Questionnaire, was administered in person to participants at two visits: between
24 and 48 hours postcesarean delivery and at 6 weeks postpartum. Descriptive
statistics, t tests, and chi(2) tests were calculated from these data and pain
descriptor selections were compared with established nociceptive and neuropathic
pain descriptor lists. RESULTS: Pain was reported in all dimensions at both
visits. The abdomen was most frequently selected for pain location; mean
intensity was 2.75/10 at the first visit, 1.1/10 at the 6-week visit. Pain in the
sensory and cognitive dimensions decreased significantly between visits.
Affective dimension pain decreased, but the difference was not significant.
Participants reported activities that increased and decreased pain in the
behavioral dimension. Pain descriptors indicative of nociceptive (e.g., tender,
sore) and neuropathic (e.g. aching) pain were selected at both visits.
CONCLUSION: Postpartum pain after cesarean delivery is multidimensional and has
been described with words indicative of nociceptive and neuropathic pain. Nurses
should complete a thorough and comprehensive pain assessment throughout the
postpartum for patients experiencing cesarean deliveries.
PMID- 25123693
TI - Evaluation of a rapid bedside scoring system for microcirculation videos acquired
from dogs.
AB - OBJECTIVE: To appraise a novel scoring system (Bedside Evaluation of
Microcirculation [BEM]) to provide qualitative and semiquantitative assessment of
canine microcirculatory videos generated by sidestream dark field imaging.
DESIGN: Prospective observational study. SETTING: University teaching hospital.
ANIMALS: No animals were used in this study. Twenty microcirculatory videos (>20
s in length) acquired from the mucosa adjacent to the upper canine tooth of dogs
were selected from a database of sidestream dark field microcirculatory videos
with available current standard analysis (CSA). INTERVENTION: Three observers
were trained to evaluate 5 video quality parameters (stability, content,
illumination, focus, and pressure) and four perfusion parameters (total vessel
density [TVD], capillary vessel density [CVD], perfused vessel density [PVD] and
microvascular flow index [MFI]). Quality parameters were scored (excellent [0],
sufficient [1], and insufficient [2]) similar to CSA recommendations. Each
perfusion parameter was subjectively scored (1 lowest - 5 highest) using sample
clips from the training video for comparison. Videos passed quality analysis if
no parameter was scored insufficient. Repeatability and reproducibility were
evaluated by assessing all films in a random order three times daily for 3 days.
Strength of correlation of BEM with CSA for both qualitative and semiquantitative
parameters was assessed. MEASUREMENTS AND MAIN RESULTS: The qualitative
evaluation pass/fail assessment matched CSA 86% of the time with individual
observer agreements of 84-88%. Agreement with CSA did not change significantly
over the study period (84%, 88%, and 84% on days 1, 2, and 3, respectively). No
significant correlations were demonstrated between any BEM perfusion parameter
and the corresponding CSA values. CONCLUSIONS: Rapid bedside assessment of
microcirculatory video quality can be achieved. However, semiquantitative
analysis by BEM demonstrated a lack of correlation with CSA for any of the
perfusion parameters assessed.
PMID- 25123694
TI - Growing medicine: small-scale cannabis cultivation for medical purposes in six
different countries.
AB - BACKGROUND: The production and consumption of cannabis for the treatment of
medical conditions is of increasing importance internationally; however, research
on different aspects of the phenomenon is still scarce. In this article, we
report findings from a cross-cultural study of small-scale cannabis cultivation
for medical purposes. This kind of comparative study has not been done
previously. METHODS: The data were gathered with a help of web surveys conducted
by the Global Cannabis Cultivation Research Consortium (GCCRC) in Australia,
Belgium, Denmark, Finland, Germany and the UK (N=5313). In the analysis we
compare reports of medical motives, for what conditions cannabis is used, whether
users have diagnoses for these conditions and whether the use of cannabis been
recommended as a treatment of those conditions by a medical doctor. Descriptive
statistics are used to show the main commonalities and noteworthy disparities
across different countries. RESULTS: Findings from countries were quite similar,
even though several national differences in details were found. Growing cannabis
for medical purposes was widespread. The majority of medical growers reported
cultivating cannabis for serious conditions. Most of them did have a formal
diagnosis. One fifth had got a recommendation from their doctor, but in most
cases cannabis use was self-medication which was not discussed with their
doctors. CONCLUSION: There is a wider demand for licit access for medical
cannabis than currently available in these countries. Ideologically, medical
growers can be seen distancing themselves from both the legal and illicit drug
markets. From a harm reduction perspective, it is worrying that, in the context
of present health and control policies in these countries, many medical growers
are using cannabis to treat serious medical conditions without proper medical
advice and doctor's guidance.
PMID- 25123695
TI - United States colorectal cancer screening practices among American Indians/Alaska
Natives, blacks, and non-Hispanic whites in the new millennium (2001 to 2010).
AB - BACKGROUND: The objectives of this study were to describe, examine, and compare
prevalence estimates of colorectal cancer (CRC) screening practices and to
determine whether disparities exist for American Indians/Alaska Natives (AIANs)
and blacks compared with whites. METHODS: Behavioral Risk Factor Surveillance
System (2001-2010) data from respondents aged >= 50 years (n = 356,073) were
used. The primary outcome was self-reported CRC screening according to US
Preventive Services Task Force guidelines for endoscopy (colonoscopy or
sigmoidoscopy), fecal occult blood test (FOBT), or mixed screening (endoscopy or
FOBT). RESULTS: From 2001 to 2010, endoscopy screening increased in the AIAN
population by 44.8% (P < .001) compared with black respondents (51.7%) and white
respondents (26.5%). AIANs were less likely to report endoscopy screening (45%)
compared with both blacks (56%) and whites (55%). For mixed CRC screenings, AIAN
rates increased by 34.5%, compared with 29.7% for blacks and 15% for whites. In
2010, AIANs (51%) had the lowest prevalence of mixed CRC screening compared with
blacks (61%) and whites (60%; P < .001). Factors that enabled health care
attenuated the lowered likelihood of CRC screenings, but disparities remained for
AIAN CRC screening. In contrast, once enabling factors were controlled, the odds
ratios of CRC screening among blacks were higher compared with whites.
CONCLUSIONS: Between 2001 and 2010, AIANs had the lowest CRC screening rates in
the United States compared with blacks and whites, presenting a CRC disparity, as
rigorously defined. The current findings indicate that, although considerable
progress has been made to increase CRC screening for blacks and whites, progress
for AIANs continues to lag behind in the first decade of 21st century.
PMID- 25123696
TI - Cangrelor: a novel intravenous antiplatelet agent with a questionable future.
AB - Current percutaneous coronary intervention (PCI) guidelines recommend the use of
a P2Y12 inhibitor with aspirin and an injectable anticoagulant. However,
available oral P2Y12 inhibitor therapy is limited by significant drug
interactions, unclear oral absorption in selected clinical conditions, and
delayed onset and offset of activity that may be cumbersome for patients
requiring coronary artery bypass graft (CABG) surgery. Cangrelor, a novel
intravenous P2Y12 inhibitor, offers potential advantages compared with currently
available oral agents, particularly in regard to rapid onset and offset of
platelet inhibition. The Cangrelor versus Standard Therapy to Achieve Optimal
Management of Platelet Inhibition (CHAMPION) trials compared cangrelor versus an
oral loading dose of clopidogrel, given before or after PCI, in patients with
both stable and acute coronary syndromes. The results were conflicting, but some
evidence demonstrated a lower rate of stent thrombosis compared with clopidogrel
and lower rates of a composite cardiovascular end point, with comparable bleeding
rates. The BRIDGE study assessed cangrelor as a replacement for oral P2Y12
inhibitors in patients awaiting CABG surgery and demonstrated that cangrelor
maintained platelet inhibition during the preoperative period and enabled a rapid
return to baseline platelet function upon cessation of the infusion. A new drug
application was submitted to the Food and Drug Administration (FDA) for use
during PCI to prevent thrombotic events and as bridging therapy for patients
awaiting surgery who require therapy with P2Y12 inhibitors. In February 2014, the
FDA's Cardiovascular and Renal Drugs Advisory Committee recommended against
approval due to concerns over an appropriate risk-benefit ratio for use during
PCI and a lack of evidence supporting the bridging indication. On April 30, 2014,
the FDA issued a Complete Response letter for the PCI and bridging indications,
denying approval and requesting further data. The future of this once promising
novel intravenous antiplatelet agent is now in question.
PMID- 25123699
TI - Selective formation and unusual reactivity of tetraarsabicyclo[1.1.0]butane
complexes.
AB - The selective formation of the dinuclear butterfly complexes
[{Cp'''Fe(CO)2}2(MU,eta(1:1)-E4)] (E = P (1 a), As (1 b)) and
[{Cp*Cr(CO)3}2(MU,eta(1:1)-E4)] (E = P (2 a), As (2 b)) as new representatives of
this rare class of compounds was found by reaction of E4 with the corresponding
dimeric carbonyl complexes. Complexes 1 b and 2 b are the first As4 butterfly
compounds with a bridging coordination mode. Moreover, first studies regarding
the reactivity of 1 b and 2 b are presented, revealing the formation of the
unprecedented As8 cuneane complexes
[{Cp'''Fe(CO)2}2{Cp'''Fe(CO)}2(MU4,eta(1:1:2:2)-As8)] (3 b) and
[{Cp*Cr(CO)3}4(MU4,eta(1:1:1:1)-As8)] (4). The compounds are fully characterized
by NMR and IR spectroscopy as well as by X-ray structure analysis. In addition,
DFT calculations give insight into the transformation pathway from the E4
butterfly to the corresponding cuneane structural motif.
PMID- 25123701
TI - Differential stigmatizing attitudes of healthcare professionals towards
psychiatry and patients with mental health problems: something to worry about? A
pilot study.
AB - PURPOSE: This study compares stigmatizing attitudes of different healthcare
professionals towards psychiatry and patients with mental health problems.
METHODS: The Mental Illness Clinicians Attitude (MICA) questionnaire is used to
assess stigmatizing attitudes in three groups: general practitioners (GPs, n =
55), mental healthcare professionals (MHCs, n = 67) and forensic psychiatric
professionals (FPs, n = 53). RESULTS: A modest positive attitude towards
psychiatry was found in the three groups (n = 176). Significant differences were
found on the total MICA-score (p < 0.001). GPs scored significantly higher than
the FPs and the latter scored significantly higher than the MHCs on all factors
of the MICA. Most stigmatizing attitudes were found on professionals' views of
health/social care field and mental illness and disclosure. Personal and work
experience did not influence stigmatizing attitudes. CONCLUSIONS: Although all
three groups have a relatively positive attitude using the MICA, there is room
for improvement. Bias toward socially acceptable answers cannot be ruled out.
Patients' view on stigmatizing attitudes of professionals may be a next step in
stigma research in professionals.
PMID- 25123703
TI - Clinical approach to endogenous lipoid pneumonia.
PMID- 25123702
TI - Diagnostic laparoscopy should be performed before definitive resection for
pancreatic cancer: a financial argument.
AB - OBJECTIVES: Laparoscopy is recommended to detect radiographically occult
metastases in patients with pancreatic cancer before curative resection. This
study was conducted to test the hypothesis that diagnostic laparoscopy (DL) is
cost-effective in patients undergoing curative resection with or without
neoadjuvant therapy (NAT). METHODS: Decision tree modelling compared routine DL
with exploratory laparotomy (ExLap) at the time of curative resection in
resectable cancer treated with surgery first, (SF) and borderline resectable
cancer treated with NAT. Costs (US$) from the payer's perspective, quality
adjusted life months (QALMs) and incremental cost-effectiveness ratios (ICERs)
were calculated. Base case estimates and multi-way sensitivity analyses were
performed. Willingness to pay (WtP) was US$4166/QALM (or US$50,000/quality
adjusted life year). RESULTS: Base case costs were US$34,921 for ExLap and
US$33,442 for DL in SF patients, and US$39,633 for ExLap and US$39,713 for DL in
NAT patients. Routine DL is the dominant (preferred) strategy in both treatment
types: it allows for cost reductions of US$10,695/QALM in SF and US$4158/QALM in
NAT patients. CONCLUSIONS: The present analysis supports the cost-effectiveness
of routine DL before curative resection in pancreatic cancer patients treated
with either SF or NAT.
PMID- 25123704
TI - An iron oxide nanocarrier for dsRNA to target lymph nodes and strongly activate
cells of the immune system.
AB - The success of nanoparticle-based therapies will depend in part on accurate
delivery to target receptors and organs. There is, therefore, considerable
potential in nanoparticles which achieve delivery of the right drug(s) using the
right route of administration to the right location at the right time, monitoring
the process by non-invasive molecular imaging. A challenge is harnessing
immunotherapy via activation of Toll-like receptors (TLRs) for the development of
vaccines against major infectious diseases and cancer. In immunotherapy, delivery
of the vaccine components to lymph nodes (LNs) is essential for effective
stimulation of the immune response. Although some promising advances have been
made, delivering therapeutics to LNs remains challenging. It is here shown that
iron-oxide nanoparticles can be engineered to combine in a single and small (<50
nm) nanocarrier complementary multimodal imaging features with the
immunostimulatory activity of polyinosinic-polycytidylic acid (poly (I:C)).
Whilst the fluorescence properties of the nanocarrier show effective delivery to
endosomes and TLR3 in antigen presenting cells, MRI/SPECT imaging reveals
effective delivery to LNs. Importantly, in vitro and in vivo studies show that,
using this nanocarrier, the immunostimulatory activity of poly (I:C) is greatly
enhanced. These nanocarriers have considerable potential for cancer diagnosis and
the development of new targeted and programmable immunotherapies.
PMID- 25123705
TI - A 4-fold-symmetry hexagonal ruthenium for magnetic heterostructures exhibiting
enhanced perpendicular magnetic anisotropy and tunnel magnetoresistance.
AB - A 4-fold-symmetry hexagonal Ru emerging in epitaxial MgO/Ru/Co2 FeAl/MgO
heterostructures is reported, in which an approximately Ru(022-3) growth
attributes to the lattice matching between MgO, Ru, and Co2 FeAl. Perpendicular
magnetic anisotropy of the Co2 FeAl/MgO interface is substantially enhanced. The
magnetic tunnel junctions (MTJs) incorporating this structure give rise to the
largest tunnel magnetoresistance for perpendicular MTJs using low damping Heusler
alloys.
PMID- 25123707
TI - Severe craniosynostosis with Noonan syndrome phenotype associated with SHOC2
mutation: clinical evidence of crosslink between FGFR and RAS signaling pathways.
AB - Dysregulation in the RAS signaling cascade results in a family of malformation
syndromes called RASopathies. Meanwhile, alterations in FGFR signaling cascade
are responsible for various syndromic forms of craniosynostosis. In general, the
phenotypic spectra of RASopathies and craniosynostosis syndromes do not overlap.
Recently, however, mutations in ERF, a downstream molecule of the RAS signaling
cascade, have been identified as a cause of complex craniosynostosis, suggesting
that the RAS and FGFR signaling pathways can interact in the pathogenesis of
malformation syndromes. Here, we document a boy with short stature, developmental
delay, and severe craniosynostosis involving right coronal, bilateral lambdoid,
and sagittal sutures with a de novo mutation in exon1 of SHOC2 (c.4A>G
p.Ser2Gly). This observation further supports the existence of a crosslink
between the RAS signaling cascade and craniosynostosis. In retrospect, the
propositus had physical features suggestive of a dysregulated RAS signaling
cascade, such as fetal pleural effusion, fetal hydrops, and atrial tachycardia.
In addition to an abnormal cranial shape, which has been reported for this
specific mutation, craniosynostosis might be a novel associated phenotype. In
conclusion, the phenotypic combination of severe craniosynostosis and RASopathy
features observed in the propositus suggests an interaction between the RAS and
FGFR signaling cascades. Patients with craniosynostosis in combination with any
RASopathy feature may require mutation screening for molecules in the FGFR-RAS
signaling cascade.
PMID- 25123708
TI - Preoperative C-reactive protein and operative blood loss predict poor prognosis
in patients with gastric cancer after laparoscopy-assisted gastrectomy.
AB - INTRODUCTION: The aim of this study was to clarify the factors associated with
postoperative complications and prognoses following laparoscopy-assisted
gastrectomy for gastric cancer. METHODS: A total of 214 patients who underwent
laparoscopy-assisted gastrectomy for gastric cancer were enrolled in this
retrospective study. Factors that were potentially associated with postoperative
complications and prognosis were assessed using the following clinical and
perioperative parameters: the Estimation of Physiologic Ability and Surgical
Stress scoring system, the Prognostic Nutritional Index, and the Clavien-Dindo
classification. RESULTS: Postoperative complications developed in 18.7% of
patients. Blood loss >= 1% of body weight was significantly correlated with
anastomotic leakage (P = 0.0108). Severe complications, based on the Clavien
Dindo classification, were more frequent in patients with proximal or total
gastrectomies (P = 0.0324). A preoperative C-reactive protein level > 0.5 mg/dL,
blood loss > 1% of body weight, age >= 70 years at the time of operation, and an
Estimation of Physiologic Ability and Surgical Stress score >= 0.2 were
significantly correlated with poor prognosis. Multivariate analysis revealed that
two of these factors, preoperative C-reactive protein level >= 0.5 mg/dL and
operative blood loss >= 1% of body weight, were independent prognostic factors (P
= 0.0376 and P = 0.0112, respectively). The Prognostic Nutritional Index had no
significant correlation with prognosis or the occurrence of postoperative
complications. CONCLUSION: Operative blood loss >= 1% of body weight and type of
resection were associated with an increased frequency of postoperative
complications, while preoperative C-reactive protein levels and operative blood
loss may be prognostic predictors for gastric cancer patients following
laparoscopy-assisted gastrectomy.
PMID- 25123706
TI - Role of autonomic reflex arcs in cardiovascular responses to air pollution
exposure.
AB - The body responds to environmental stressors by triggering autonomic reflexes in
the pulmonary receptors, baroreceptors, and chemoreceptors to maintain
homeostasis. Numerous studies have shown that exposure to various gases and
airborne particles can alter the functional outcome of these reflexes,
particularly with respect to the cardiovascular system. Modulation of autonomic
neural input to the heart and vasculature following direct activation of sensory
nerves in the respiratory system, elicitation of oxidative stress and
inflammation, or through other mechanisms is one of the primary ways that
exposure to air pollution affects normal cardiovascular function. Any homeostatic
process that utilizes the autonomic nervous system to regulate organ function
might be affected. Thus, air pollution and other inhaled environmental irritants
have the potential to alter both local airway function and baro- and chemoreflex
responses, which modulate autonomic control of blood pressure and detect
concentrations of key gases in the body. While each of these reflex pathways
causes distinct responses, the systems are heavily integrated and communicate
through overlapping regions of the brainstem to cause global effects. This short
review summarizes the function of major pulmonary sensory receptors,
baroreceptors, and carotid body chemoreceptors and discusses the impacts of air
pollution exposure on these systems.
PMID- 25123710
TI - Female genital mutilation/cutting: will it continue?
AB - INTRODUCTION: Female genital mutilation/cutting (FGM/C) is a prevalent, deeply
rooted traditional practice in Egypt. AIMS: Specification of the motives behind
the continuation of FGM/C in Egyptian community and evaluation of the sexual
function in women with FGM/C. METHODS: This cross-sectional study, involved 2,106
sexually active female participants with FGM/C. Full history-taking and general
examination to evaluate the type of FGM/C were conducted. Sexual function was
assessed by using the Female Sexual Function Index (FSFI) questionnaire. MAIN
OUTCOME MEASURES: Enumerate and specify the motivational factors and its percent
among the participants. The correlation between FGM/C and FSFI domain scores was
done with Pearson's correlation. RESULTS: Tradition, cleanliness, and virginity
were the most common motives empowering the continuation of FGM/C (100%),
followed by men's wish, esthetic factors, marriage, and religion factors (45.2
100%). Type I FGM/C was the most common, followed by type II. There was only
negative correlation between the type II FGM/C and sexual satisfaction. No
statistically significant difference between type I and non-FGM/C was found.
CONCLUSIONS: FGM/C remains high. A variety of socio-cultural myths, religious
misbelievers, and hygienic and esthetic concerns were behind the FGM/C. Overall,
a large proportion of the participants supported the continuation of FGM/C in
spite of adverse effect and sexual dysfunction associated with FGM/C.
PMID- 25123711
TI - Forecast-based interventions can reduce the health and economic burden of
wildfires.
AB - We simulated public health forecast-based interventions during a wildfire smoke
episode in rural North Carolina to show the potential for use of modeled smoke
forecasts toward reducing the health burden and showed a significant economic
benefit of reducing exposures. Daily and county wide intervention advisories were
designed to occur when fine particulate matter (PM2.5) from smoke, forecasted 24
or 48 h in advance, was expected to exceed a predetermined threshold. Three
different thresholds were considered in simulations, each with three different
levels of adherence to the advisories. Interventions were simulated in the adult
population susceptible to health exacerbations related to the chronic conditions
of asthma and congestive heart failure. Associations between Emergency Department
(ED) visits for these conditions and daily PM2.5 concentrations under each
intervention were evaluated. Triggering interventions at lower PM2.5 thresholds
(<= 20 MUg/m(3)) with good compliance yielded the greatest risk reduction. At the
highest threshold levels (50 MUg/m(3)) interventions were ineffective in reducing
health risks at any level of compliance. The economic benefit of effective
interventions exceeded $1 M in excess ED visits for asthma and heart failure, $2
M in loss of productivity, $100 K in respiratory conditions in children, and $42
million due to excess mortality.
PMID- 25123712
TI - Molecular modeling in dioxane methanol interaction.
AB - Molecular interaction between dioxane and methanol involves certain polar and
nonpolar bonding to form a one to one complex. Interatomic distances between
hydrogen and oxygen within 3 A have been considered as hydrogen bonding.
Optimizations of the structures of dioxane-methanol complexes were carried out
considering any spatial orientation of a methanol molecule around a
chair/boat/twisted-boat conformation of dioxane. From 45 different orientations
of dioxane and water, 23 different structures with different local minima were
obtained and the structural characteristics like interatomic distances, bond
angles, dihedral angles, dipole moment of each complex were discussed. The most
stable structure, i.e., with minimum heat of formation is found to have a chair
form dioxane, one O-H...O, and two C-H...O hydrogen bonds. In general, the O
H...O hydrogen bonds have an average distance of 1.8 A while C-H...O bonds have
2.6 A. The binding energy of the dioxane-methanol complex is found to be a linear
function of number of O-H...O and C-H...O bonds, and hydrogen bond length.
PMID- 25123714
TI - The Other Side(s) of Health Informatics.
PMID- 25123713
TI - Accesses to electronic structures and the excited states of blue luminescent
copper(I) complexes containing N-heterocyclic carbene ligands: a DFT/TDDFT
exploitation.
AB - The ground electronic states and photophysical properties of three designed Cu(I)
complexes [Cu(ImNHC)(POP)](+) (1), [Cu(methyl-ImNHC)(POP)](+) (2), and
[Cu(BenzImNHC)(POP)](+) (3); where [ImNHC = 3-methyl-1-(pyridin-2-yl)-1H-imidazol
2-ylidene; methyl-ImNHC = 3-methyl-1-(pyridin-2-ylmethyl)-1H-imidazol-2-ylidene;
BenzImNHC = 3-methyl-1-(pyridin-2-yl)-1H-benzimidazol-2-ylidene], have been
investigated using density functional theory (DFT) and time-dependent density
functional theory (TDDFT). The results reveal that the presence of the methylene
spacer in the NHC ligands has a more direct effect on the distribution of
frontier molecular orbitals while the elongation of pi conjugation provided by
the fused imidazole in the NHC ligands has a negligible effect. The UV-vis
absorption spectra of all the complexes are well produced by TD-DFT calculations
based on the charge transfer amount calculations and the corresponding band
assignments are discussed. Importantly, the triplet energy calculations
demonstrated that complex 2 would be a highly efficient blue emitter with the
deep-blue of 440 nm.
PMID- 25123715
TI - Francois Gremy, a humanist and information sciences pioneer.
PMID- 25123716
TI - Big data in medicine is driving big changes.
AB - OBJECTIVES: To summarise current research that takes advantage of "Big Data" in
health and biomedical informatics applications. METHODS: Survey of trends in this
work, and exploration of literature describing how large-scale structured and
unstructured data sources are being used to support applications from clinical
decision making and health policy, to drug design and pharmacovigilance, and
further to systems biology and genetics. RESULTS: The survey highlights ongoing
development of powerful new methods for turning that large-scale, and often
complex, data into information that provides new insights into human health, in a
range of different areas. Consideration of this body of work identifies several
important paradigm shifts that are facilitated by Big Data resources and methods:
in clinical and translational research, from hypothesis-driven research to data
driven research, and in medicine, from evidence-based practice to practice-based
evidence. CONCLUSIONS: The increasing scale and availability of large quantities
of health data require strategies for data management, data linkage, and data
integration beyond the limits of many existing information systems, and
substantial effort is underway to meet those needs. As our ability to make sense
of that data improves, the value of the data will continue to increase. Health
systems, genetics and genomics, population and public health; all areas of
biomedicine stand to benefit from Big Data and the associated technologies.
PMID- 25123717
TI - Big Data in Science and Healthcare: A Review of Recent Literature and
Perspectives. Contribution of the IMIA Social Media Working Group.
AB - OBJECTIVES: As technology continues to evolve and rise in various industries,
such as healthcare, science, education, and gaming, a sophisticated concept known
as Big Data is surfacing. The concept of analytics aims to understand data. We
set out to portray and discuss perspectives of the evolving use of Big Data in
science and healthcare and, to examine some of the opportunities and challenges.
METHODS: A literature review was conducted to highlight the implications
associated with the use of Big Data in scientific research and healthcare
innovations, both on a large and small scale. RESULTS: Scientists and health-care
providers may learn from one another when it comes to understanding the value of
Big Data and analytics. Small data, derived by patients and consumers, also
requires analytics to become actionable. Connectivism provides a framework for
the use of Big Data and analytics in the areas of science and healthcare. This
theory assists individuals to recognize and synthesize how human connections are
driving the increase in data. Despite the volume and velocity of Big Data, it is
truly about technology connecting humans and assisting them to construct
knowledge in new ways. Concluding Thoughts: The concept of Big Data and
associated analytics are to be taken seriously when approaching the use of vast
volumes of both structured and unstructured data in science and health-care.
Future exploration of issues surrounding data privacy, confidentiality, and
education are needed. A greater focus on data from social media, the quantified
self-movement, and the application of analytics to "small data" would also be
useful.
PMID- 25123719
TI - Challenges and potential solutions for big data implementations in developing
countries.
AB - BACKGROUND: The volume of data, the velocity with which they are generated, and
their variety and lack of structure hinder their use. This creates the need to
change the way information is captured, stored, processed, and analyzed, leading
to the paradigm shift called Big Data. OBJECTIVES: To describe the challenges and
possible solutions for developing countries when implementing Big Data projects
in the health sector. METHODS: A non-systematic review of the literature was
performed in PubMed and Google Scholar. The following keywords were used: "big
data", "developing countries", "data mining", "health information systems", and
"computing methodologies". A thematic review of selected articles was performed.
RESULTS: There are challenges when implementing any Big Data program including
exponential growth of data, special infrastructure needs, need for a trained
workforce, need to agree on interoperability standards, privacy and security
issues, and the need to include people, processes, and policies to ensure their
adoption. Developing countries have particular characteristics that hinder
further development of these projects. CONCLUSIONS: The advent of Big Data
promises great opportunities for the healthcare field. In this article, we
attempt to describe the challenges developing countries would face and enumerate
the options to be used to achieve successful implementations of Big Data
programs.
PMID- 25123718
TI - Big Data Usage Patterns in the Health Care Domain: A Use Case Driven Approach
Applied to the Assessment of Vaccination Benefits and Risks. Contribution of the
IMIA Primary Healthcare Working Group.
AB - BACKGROUND: Generally benefits and risks of vaccines can be determined from
studies carried out as part of regulatory compliance, followed by surveillance of
routine data; however there are some rarer and more long term events that require
new methods. Big data generated by increasingly affordable personalised
computing, and from pervasive computing devices is rapidly growing and low cost,
high volume, cloud computing makes the processing of these data inexpensive.
OBJECTIVE: To describe how big data and related analytical methods might be
applied to assess the benefits and risks of vaccines. METHOD: We reviewed the
literature on the use of big data to improve health, applied to generic vaccine
use cases, that illustrate benefits and risks of vaccination. We defined a use
case as the interaction between a user and an information system to achieve a
goal. We used flu vaccination and pre-school childhood immunisation as exemplars.
RESULTS: We reviewed three big data use cases relevant to assessing vaccine
benefits and risks: (i) Big data processing using crowdsourcing, distributed big
data processing, and predictive analytics, (ii) Data integration from
heterogeneous big data sources, e.g. the increasing range of devices in the
"internet of things", and (iii) Real-time monitoring for the direct monitoring of
epidemics as well as vaccine effects via social media and other data sources.
CONCLUSIONS: Big data raises new ethical dilemmas, though its analysis methods
can bring complementary real-time capabilities for monitoring epidemics and
assessing vaccine benefit-risk balance.
PMID- 25123720
TI - Technical challenges for big data in biomedicine and health: data sources,
infrastructure, and analytics.
AB - OBJECTIVES: To review technical and methodological challenges for big data
research in biomedicine and health. METHODS: We discuss sources of big datasets,
survey infrastructures for big data storage and big data processing, and describe
the main challenges that arise when analyzing big data. RESULTS: The life and
biomedical sciences are massively contributing to the big data revolution through
secondary use of data that were collected during routine care and through new
data sources such as social media. Efficient processing of big datasets is
typically achieved by distributing computation over a cluster of computers. Data
analysts should be aware of pitfalls related to big data such as bias in routine
care data and the risk of false-positive findings in high-dimensional datasets.
CONCLUSIONS: The major challenge for the near future is to transform analytical
methods that are used in the biomedical and health domain, to fit the distributed
storage and processing model that is required to handle big data, while ensuring
confidentiality of the data being analyzed.
PMID- 25123721
TI - Big data - smart health strategies. Findings from the yearbook 2014 special
theme.
AB - OBJECTIVES: To select best papers published in 2013 in the field of big data and
smart health strategies, and summarize outstanding research efforts. METHODS: A
systematic search was performed using two major bibliographic databases for
relevant journal papers. The references obtained were reviewed in a two-stage
process, starting with a blinded review performed by the two section editors, and
followed by a peer review process operated by external reviewers recognized as
experts in the field. RESULTS: The complete review process selected four best
papers, illustrating various aspects of the special theme, among them: (a) using
large volumes of unstructured data and, specifically, clinical notes from
Electronic Health Records (EHRs) for pharmacovigilance; (b) knowledge discovery
via querying large volumes of complex (both structured and unstructured)
biological data using big data technologies and relevant tools; (c) methodologies
for applying cloud computing and big data technologies in the field of genomics,
and (d) system architectures enabling high-performance access to and processing
of large datasets extracted from EHRs. CONCLUSIONS: The potential of big data in
biomedicine has been pinpointed in various viewpoint papers and editorials. The
review of current scientific literature illustrated a variety of interesting
methods and applications in the field, but still the promises exceed the current
outcomes. As we are getting closer towards a solid foundation with respect to
common understanding of relevant concepts and technical aspects, and the use of
standardized technologies and tools, we can anticipate to reach the potential
that big data offer for personalized medicine and smart health strategies in the
near future.
PMID- 25123722
TI - Reuse of clinical data.
AB - OBJECTIVES: To provide an overview of the benefits of clinical data collected as
a by-product of the care process, the potential problems with large aggregations
of these data, the policy frameworks that have been formulated, and the major
challenges in the coming years. METHODS: This report summarizes some of the major
observations from AMIA and IMIA conferences held on this admittedly broad topic
from 2006 through 2013. This report also includes many unsupported opinions of
the author. RESULTS: The benefits of aggregating larger and larger sets of
routinely collected clinical data are well documented and of great societal
benefit. These large data sets will probably never answer all possible clinical
questions for methodological reasons. Non-traditional sources of health data that
are patient-sources will pose new data science challenges. CONCLUSIONS: If we
ever hope to have tools that can rapidly provide evidence for daily practice of
medicine we need a science of health data perhaps modeled after the science of
astronomy.
PMID- 25123723
TI - Trends on integrating framework of applications or data. Findings from the
section on health and clinical management.
AB - OBJECTIVE: To summarize current excellent research and trends in the field of
Health and Clinical management. METHODS: Synopsis of the articles selected for
the IMIA Yearbook 21014 RESULTS: A comprehensive review of papers published in
2013 was performed by querying PubMed. 1079 were reviewed as papers without
authors, without abstract or smaller than 4 pages were excluded from the
selection. The editors reviewed all papers and 15 papers selected and provided to
to international reviewers. Four papers from international peer-reviewed journals
were finally selected for the Health and Clinical Management section. CONCLUSION:
Many telemedicine applications are tested nowadays in medical situation, but the
challenges emphasized by the best papers selection focus on the ability of
proposing integrative frameworks for applications or data in order to handle
efficiency of health and clinical management.
PMID- 25123725
TI - Human Factors in the Large: Experiences from Denmark, Finland and Canada in
Moving Towards Regional and National Evaluations of Health Information System
Usability. Contribution of the IMIA Human Factors Working Group.
AB - OBJECTIVES: The objective of this paper is to explore approaches to understanding
the usability of health information systems at regional and national levels.
METHODS: Several different methods are discussed in case studies from Denmark,
Finland and Canada. They range from small scale qualitative studies involving
usability testing of systems to larger scale national level questionnaire studies
aimed at assessing the use and usability of health information systems by entire
groups of health professionals. RESULTS: It was found that regional and national
usability studies can complement smaller scale usability studies, and that they
are needed in order to understand larger trends regarding system usability.
Despite adoption of EHRs, many health professionals rate the usability of the
systems as low. A range of usability issues have been noted when data is
collected on a large scale through use of widely distributed questionnaires and
websites designed to monitor user perceptions of usability. CONCLUSION: As health
information systems are deployed on a widespread basis, studies that examine
systems used regionally or nationally are required. In addition, collection of
large scale data on the usability of specific IT products is needed in order to
complement smaller scale studies of specific systems.
PMID- 25123724
TI - Human factors and health information technology: current challenges and future
directions.
AB - OBJECTIVES: Recent federal mandates and incentives have spurred the rapid growth,
development and adoption of health information technology (HIT). While providing
significant benefits for better data integration, organization, and availability,
recent reports have raised questions regarding their potential to cause
medication errors, decreased clinician performance, and lowered efficiency. The
goal of this survey article is to (a) examine the theoretical and foundational
models of human factors and ergonomics (HFE) that are being advocated for
achieving patient safety and quality, and their use in the evaluation of
healthcare systems; (b) and the potential for macroergonomic HFE approaches
within the context of current research in biomedical informatics. METHODS: We
reviewed literature (2007-2013) on the use of HFE approaches in healthcare
settings, from databases such as Pubmed, CINAHL, and Cochran. RESULTS: Based on
the review, we discuss the systems-oriented models, their use in the evaluation
of HIT, and examples of their use in the evaluation of EHR systems, clinical
workflow processes, and medication errors. We also discuss the opportunities for
better integrating HFE methods within biomedical informatics research and its
potential advantages. CONCLUSIONS: The use of HFE methods is still in its infancy
- better integration of HFE within the design lifecycle, and quality improvement
efforts can further the ability of informatics researchers to address the key
concerns regarding the complexity in clinical settings and develop HIT solutions
that are designed within the social fabric of the considered setting.
PMID- 25123726
TI - Big Data in Healthcare - Defining the Digital Persona through User Contexts from
the Micro to the Macro. Contribution of the IMIA Organizational and Social Issues
WG.
AB - OBJECTIVES: While big data offers enormous potential for improving healthcare
delivery, many of the existing claims concerning big data in healthcare are based
on anecdotal reports and theoretical vision papers, rather than scientific
evidence based on empirical research. Historically, the implementation of health
information technology has resulted in unintended consequences at the individual,
organizational and social levels, but these unintended consequences of collecting
data have remained unaddressed in the literature on big data. The objective of
this paper is to provide insights into big data from the perspective of people,
social and organizational considerations. METHOD: We draw upon the concept of
persona to define the digital persona as the intersection of data, tasks and
context for different user groups. We then describe how the digital persona can
serve as a framework to understanding sociotechnical considerations of big data
implementation. We then discuss the digital persona in the context of micro, meso
and macro user groups across the 3 Vs of big data. RESULTS: We provide insights
into the potential benefits and challenges of applying big data approaches to
healthcare as well as how to position these approaches to achieve health system
objectives such as patient safety or patient-engaged care delivery. We also
provide a framework for defining the digital persona at a micro, meso and macro
level to help understand the user contexts of big data solutions. CONCLUSION:
While big data provides great potential for improving healthcare delivery, it is
essential that we consider the individual, social and organizational contexts of
data use when implementing big data solutions.
PMID- 25123727
TI - Reasons (not) to Spend a Few Billions More on EHRs: How Human Factors Research
Can Help.
AB - OBJECTIVES: To select best medical informatics research works published in 2013
on electronic health record (EHR) adoption, design, and impact, from the
perspective of human factors and organizational issues (HFOI). METHODS: We
selected 2,764 papers by querying PubMed (Mesh and TIAB) as well as using a
manual search. Papers were evaluated based on pre-defined exclusion and inclusion
criteria from their title, keywords, and abstract to select 15 candidate best
papers, finally reviewed by 4 external reviewers using a standard evaluation
grid. RESULTS: Five papers were selected as best papers to illustrate how human
factors approaches can improve EHR adoption and design. Among other
contributions, these works: (i) make use of the observational and analysis
methodologies of social and cognitive sciences to understand clinicians'
attitudes towards EHRs, EHR use patterns, and impact on care processes,
workflows, information exchange, and coordination of care; (ii) take into account
macro- (environmental) and meso- (organizational) level factors to analyze EHR
adoption or lack thereof; (iii) highlight the need for qualitative studies to
analyze the unexpected side effects of EHRs on cognitive and work processes as
well as the persistent use of paper. CONCLUSION: Selected papers tend to
demonstrate that HFOI approaches and methodologies are essential to bridge the
gap between EHR systems and end users, and to reduce regularly reported adoption
failures and unexpected consequences.
PMID- 25123729
TI - Future Direction of IMIA Standardization. Report from the IMIA Standardization
Working Group.
AB - OBJECTIVES: Standardization in the field of health informatics has increased its
importance and global alliance for establishing interoperability and
compatibility internationally. Standardization has been organized by standard
development organizations (SDOs) such as ISO (International Organization for
Standardization), CEN (European Committee for Standardization), IHE (Integrating
the Healthcare Enterprise), and HL7 (Health Level 7), etc. This paper reports the
status of these SDOs' activities. METHODS: In this workshop, we reviewed the past
activities and the current situation of standardization in health care
informatics with the standard development organizations such as ISO, CEN, IHE,
and HL7. Then we discussed the future direction of standardization in health
informatics toward "future medicine" based on standardized technologies. RESULTS:
We could share the status of each SDO through exchange of opinions in the
workshop. Some WHO members joined our discussion to support this constructive
activity. CONCLUSION: At this meeting, the workshop speakers have been appointed
as new members of the IMIA working groups of Standards in Health Care Informatics
(WG16). We could reach to the conclusion that we collaborate for the
international standardization in health informatics toward "future medicine".
PMID- 25123731
TI - Big data and smart health strategies: findings from the health information
systems perspective.
AB - OBJECTIVES: To summarize excellent current research in the field of Health
Information Systems. METHOD: Creation of a synopsis of the articles selected for
the 2014 edition of the IMIA Yearbook. RESULTS: Four papers from international
peer reviewed journals were selected and are summarized. CONCLUSIONS: Selected
articles illustrate current research regarding the impact and the evaluation of
health information technology and the latest developments in health information
exchange.
PMID- 25123728
TI - "Big data" and the electronic health record.
AB - OBJECTIVES: Implementation of Electronic Health Record (EHR) systems continues to
expand. The massive number of patient encounters results in high amounts of
stored data. Transforming clinical data into knowledge to improve patient care
has been the goal of biomedical informatics professionals for many decades, and
this work is now increasingly recognized outside our field. In reviewing the
literature for the past three years, we focus on "big data" in the context of EHR
systems and we report on some examples of how secondary use of data has been put
into practice. METHODS: We searched PubMed database for articles from January 1,
2011 to November 1, 2013. We initiated the search with keywords related to "big
data" and EHR. We identified relevant articles and additional keywords from the
retrieved articles were added. Based on the new keywords, more articles were
retrieved and we manually narrowed down the set utilizing predefined inclusion
and exclusion criteria. RESULTS: Our final review includes articles categorized
into the themes of data mining (pharmacovigilance, phenotyping, natural language
processing), data application and integration (clinical decision support,
personal monitoring, social media), and privacy and security. CONCLUSION: The
increasing adoption of EHR systems worldwide makes it possible to capture large
amounts of clinical data. There is an increasing number of articles addressing
the theme of "big data", and the concepts associated with these articles vary.
The next step is to transform healthcare big data into actionable knowledge.
PMID- 25123733
TI - What Does Big Data Mean for Wearable Sensor Systems? Contribution of the IMIA
Wearable Sensors in Healthcare WG.
AB - OBJECTIVES: The aim of this paper is to discuss how recent developments in the
field of big data may potentially impact the future use of wearable sensor
systems in healthcare. METHODS: The article draws on the scientific literature to
support the opinions presented by the IMIA Wearable Sensors in Healthcare Working
Group. RESULTS: The following is discussed: the potential for wearable sensors to
generate big data; how complementary technologies, such as a smartphone, will
augment the concept of a wearable sensor and alter the nature of the monitoring
data created; how standards would enable sharing of data and advance scientific
progress. Importantly, attention is drawn to statistical inference problems for
which big datasets provide little assistance, or may hinder the identification of
a useful solution. Finally, a discussion is presented on risks to privacy and
possible negative consequences arising from intensive wearable sensor monitoring.
CONCLUSIONS: Wearable sensors systems have the potential to generate datasets
which are currently beyond our capabilities to easily organize and interpret. In
order to successfully utilize wearable sensor data to infer wellbeing, and enable
proactive health management, standards and ontologies must be developed which
allow for data to be shared between research groups and between commercial
systems, promoting the integration of these data into health information systems.
However, policy and regulation will be required to ensure that the detailed
nature of wearable sensor data is not misused to invade privacies or prejudice
against individuals.
PMID- 25123732
TI - Are electronic cardiac devices still evolving?
AB - OBJECTIVES: The goal of this paper is to review some important issues occurring
during the past year in Implantable devices. METHODS: First cardiac implantable
device was proposed to maintain an adequate heart rate, either because the
heart's natural pacemaker is not fast enough, or there is a block in the heart's
electrical conduction system. During the last forty years, pacemakers have
evolved considerably and become programmable and allow to configure specific
patient optimum pacing modes. Various technological aspects (electrodes,
connectors, algorithms diagnosis, therapies, ...) have been progressed and
cardiac implants address several clinical applications: management of
arrhythmias, cardioversion / defibrillation and cardiac resynchronization
therapy. RESULTS: Observed progress was the miniaturization of device, increased
longevity, coupled with efficient pacing functions, multisite pacing modes,
leadless pacing and also a better recognition of supraventricular or ventricular
tachycardia's in order to deliver appropriate therapy. Subcutaneous implant, new
modes of stimulation (leadless implant or ultrasound lead), quadripolar lead and
new sensor or new algorithm for the hemodynamic management are introduced and
briefly described. Each times, the main result occurring during the two past
years are underlined and repositioned from the history, remaining limitations are
also addressed. CONCLUSION: Some important technological improvements were
described. Nevertheless, news trends for the future are also considered in a
specific session such as the remote follow-up of the patient or the treatment of
heart failure by neuromodulation.
PMID- 25123730
TI - A Review and Framework for Categorizing Current Research and Development in
Health Related Geographical Information Systems (GIS) Studies.
AB - OBJECTIVES: The application of GIS in health science has increased over the last
decade and new innovative application areas have emerged. This study reviews the
literature and builds a framework to provide a conceptual overview of the domain,
and to promote strategic planning for further research of GIS in health. METHOD:
The framework is based on literature from the library databases Scopus and Web of
Science. The articles were identified based on keywords and initially selected
for further study based on titles and abstracts. A grounded theory-inspired
method was applied to categorize the selected articles in main focus areas.
Subsequent frequency analysis was performed on the identified articles in areas
of infectious and non-infectious diseases and continent of origin. RESULTS: A
total of 865 articles were included. Four conceptual domains within GIS in health
sciences comprise the framework: spatial analysis of disease, spatial analysis of
health service planning, public health, health technologies and tools. Frequency
analysis by disease status and location show that malaria and schistosomiasis are
the most commonly analyzed infectious diseases where cancer and asthma are the
most frequently analyzed non-infectious diseases. Across categories, articles
from North America predominate, and in the category of spatial analysis of
diseases an equal number of studies concern Asia. CONCLUSION: Spatial analysis of
diseases and health service planning are well-established research areas. The
development of future technologies and new application areas for GIS and data
gathering technologies such as GPS, smartphones, remote sensing etc. will be
nudging the research in GIS and health.
PMID- 25123734
TI - Big data, smart homes and ambient assisted living.
AB - OBJECTIVES: To discuss how current research in the area of smart homes and
ambient assisted living will be influenced by the use of big data. METHODS: A
scoping review of literature published in scientific journals and conference
proceedings was performed, focusing on smart homes, ambient assisted living and
big data over the years 2011-2014. RESULTS: The health and social care market has
lagged behind other markets when it comes to the introduction of innovative IT
solutions and the market faces a number of challenges as the use of big data will
increase. First, there is a need for a sustainable and trustful information chain
where the needed information can be transferred from all producers to all
consumers in a structured way. Second, there is a need for big data strategies
and policies to manage the new situation where information is handled and
transferred independently of the place of the expertise. Finally, there is a
possibility to develop new and innovative business models for a market that
supports cloud computing, social media, crowdsourcing etc. CONCLUSIONS: The
interdisciplinary area of big data, smart homes and ambient assisted living is no
longer only of interest for IT developers, it is also of interest for decision
makers as customers make more informed choices among today's services. In the
future it will be of importance to make information usable for managers and
improve decision making, tailor smart home services based on big data, develop
new business models, increase competition and identify policies to ensure
privacy, security and liability.
PMID- 25123735
TI - Sensor, signal, and imaging informatics: big data and smart health technologies.
AB - OBJECTIVES: This synopsis presents a selection for the IMIA (International
Medical Informatics Association) Yearbook 2014 of excellent research in the broad
field of Sensor, Signal, and Imaging Informatics published in the year 2013, with
a focus on Big Data and Smart Health Technologies Methods: We performed a
systematic initial selection and a double blind peer review process to find the
best papers in this domain published in 2013, from the PubMed and Web of Science
databases. A set of MeSH keywords provided by experts was used. RESULTS: Big Data
are collections of large and complex datasets which have the potential to capture
the whole variability of a study population. More and more innovative sensors are
emerging, allowing to enrich these big databases. However they become more and
more challenging to process (i.e. capture, store, search, share, transfer,
exploit) because traditional tools are not adapted anymore. CONCLUSIONS: This
review shows that it is necessary not only to develop new tools specifically
designed for Big Data, but also to evaluate their performance on such large
datasets.
PMID- 25123736
TI - IBM's Health Analytics and Clinical Decision Support.
AB - OBJECTIVES: This survey explores the role of big data and health analytics
developed by IBM in supporting the transformation of healthcare by augmenting
evidence-based decision-making. METHODS: Some problems in healthcare and
strategies for change are described. It is argued that change requires better
decisions, which, in turn, require better use of the many kinds of healthcare
information. Analytic resources that address each of the information challenges
are described. Examples of the role of each of the resources are given. RESULTS:
There are powerful analytic tools that utilize the various kinds of big data in
healthcare to help clinicians make more personalized, evidenced-based decisions.
Such resources can extract relevant information and provide insights that
clinicians can use to make evidence-supported decisions. There are early
suggestions that these resources have clinical value. As with all analytic tools,
they are limited by the amount and quality of data. CONCLUSION: Big data is an
inevitable part of the future of healthcare. There is a compelling need to manage
and use big data to make better decisions to support the transformation of
healthcare to the personalized, evidence-supported model of the future. Cognitive
computing resources are necessary to manage the challenges in employing big data
in healthcare. Such tools have been and are being developed. The analytic
resources, themselves, do not drive, but support healthcare transformation.
PMID- 25123737
TI - A 2014 medical informatics perspective on clinical decision support systems: do
we hit the ceiling of effectiveness?
AB - OBJECTIVE: To summarize recent research and propose a selection of best papers
published in 2013 in the field of computer-based decision support in health care.
METHOD: Two literature reviews were performed by the two section editors from
bibliographic databases with a focus on clinical decision support systems (CDSSs)
and computer provider order entry in order to select a list of candidate best
papers to be peer-reviewed by external reviewers. RESULTS: The full review
process highlighted three papers, illustrating current trends in the domain of
clinical decision support. The first trend is the development of theoretical
approaches for CDSSs, and is exemplified by a paper proposing the integration of
family histories and pedigrees in a CDSS. The second trend is illustrated by well
designed CDSSs, showing good theoretical performances and acceptance, while
failing to show a clinical impact. An example is given with a paper reporting on
scorecards aiming to reduce adverse drug events. The third trend is represented
by research works that try to understand the limits of CDSS use, for instance by
analyzing interactions between general practitioners, patients, and a CDSS.
CONCLUSIONS: CDSSs can achieve good theoretical results in terms of sensibility
and specificity, as well as a good acceptance, but evaluations often fail to
demonstrate a clinical impact. Future research is needed to better understand the
causes of this observation and imagine new effective solutions for CDSS
implementation.
PMID- 25123738
TI - Managing free text for secondary use of health data.
AB - OBJECTIVE: To summarize the best papers in the field of Knowledge Representation
and Management (KRM). METHODS: A comprehensive review of medical informatics
literature was performed to select some of the most interesting papers of KRM and
natural language processing (NLP) published in 2013. RESULTS: Four articles were
selected, one focuses on Electronic Health Record (EHR) interoperability for
clinical pathway personalization based on structured data. The other three focus
on NLP (corpus creation, de-identification, and co-reference resolution) and
highlight the increase in NLP tools performances. CONCLUSION: NLP tools are close
to being seriously concurrent to humans in some annotation tasks. Their use could
increase drastically the amount of data usable for meaningful use of EHR.
PMID- 25123739
TI - Transforming health care delivery through consumer engagement, health data
transparency, and patient-generated health information.
AB - OBJECTIVE: Address current topics in consumer health informatics. METHODS:
Literature review. RESULTS: Current health care delivery systems need to be more
effective in the management of chronic conditions as the population turns older
and experiences escalating chronic illness that threatens to consume more health
care resources than countries can afford. Most health care systems are positioned
poorly to accommodate this. Meanwhile, the availability of ever more powerful and
cheaper information and communication technology, both for professionals and
consumers, has raised the capacity to gather and process information, communicate
more effectively, and monitor the quality of care processes. CONCLUSION: Adapting
health care systems to serve current and future needs requires new streams of
data to enable better self-management, improve shared decision making, and
provide more virtual care. Changes in reimbursement for health care services,
increased adoption of relevant technologies, patient engagement, and calls for
data transparency raise the importance of patient-generated health information,
remote monitoring, non-visit based care, and other innovative care approaches
that foster more frequent contact with patients and better management of chronic
conditions.
PMID- 25123740
TI - Big Data: Are Biomedical and Health Informatics Training Programs Ready?
Contribution of the IMIA Working Group for Health and Medical Informatics
Education.
AB - OBJECTIVE: The growing volume and diversity of health and biomedical data
indicate that the era of Big Data has arrived for healthcare. This has many
implications for informatics, not only in terms of implementing and evaluating
information systems, but also for the work and training of informatics
researchers and professionals. This article addresses the question: What do
biomedical and health informaticians working in analytics and Big Data need to
know? METHODS: We hypothesize a set of skills that we hope will be discussed
among academic and other informaticians. RESULTS: The set of skills includes:
Programming - especially with data-oriented tools, such as SQL and statistical
programming languages; Statistics - working knowledge to apply tools and
techniques; Domain knowledge - depending on one's area of work, bioscience or
health care; and Communication - being able to understand needs of people and
organizations, and articulate results back to them. CONCLUSION: Biomedical and
health informatics educational programs must introduce concepts of analytics, Big
Data, and the underlying skills to use and apply them into their curricula. The
development of new coursework should focus on those who will become experts, with
training aiming to provide skills in "deep analytical talent" as well as those
who need knowledge to support such individuals.
PMID- 25123741
TI - Engaging Patients through Mobile Phones: Demonstrator Services, Success Factors,
and Future Opportunities in Low and Middle-income Countries.
AB - OBJECTIVES: Evolving technology and infrastructure can benefit patients even in
the poorest countries through mobile health (mHealth). Yet, what makes mobile
phone-based services succeed in low and middle-income countries (LMIC) and what
opportunities does the future hold that still need to be studied. We showcase
demonstrator services that leverage mobile phones in the hands of patients to
promote health and facilitate health care. METHODS: We surveyed the recent
biomedical literature for demonstrator services that illustrate well-considered
examples of mobile phone interventions for consumer health. We draw upon those
examples to discuss enabling factors, scalability, reach, and potential of
mHealth as well as obstacles in LMIC. RESULTS: Among the 227 articles returned by
a PubMed search, we identified 55 articles that describe services targeting
health consumers equipped with mobile phones. From those articles, we showcase 19
as demonstrator services across clinical care, prevention, infectious diseases,
and population health. Services range from education, reminders, reporting, and
peer support, to epidemiologic reporting, and care management with phone
communication and messages. Key achievements include timely adherence to
treatment and appointments, clinical effectiveness of treatment reminders,
increased vaccination coverage and uptake of screening, and capacity for
efficient disease surveillance. We discuss methodologies of delivery and
evaluation of mobile-phone-based mHealth in LMIC, including service design,
social context, and environmental factors to success. CONCLUSION: Demonstrated
promises using mobile phones in the poorest countries encourage a future in which
IMIA takes a lead role in leveraging mHealth for citizen empowerment through
Consumer Health Informatics.
PMID- 25123742
TI - Social media and patient health outcomes. Findings from the yearbook 2014 section
on consumer health informatics.
AB - OBJECTIVES: To provide a review of the current excellent research published in
the field of Consumer Health Informatics. METHOD: We searched MEDLINE(r) and WEB
OF SCIENCE(r) databases for papers published in 2013 in relation with Consumer
Health Informatics. The authors identified 16 candidate best papers, which were
then reviewed by four reviewers. RESULTS: Five out of the 16 candidate papers
were selected as best papers. One paper presents the key features of a system to
automate the collection of web-based social media content for subsequent semantic
annotation. This paper emphasizes the importance of mining social media to
collect novel data from which new findings in drug abuse research were uncovered.
The second paper presents a practical method to predict how a community structure
would impact the spreading of information within the community. The third paper
presents a method for improving the quality of online health communities. The
fourth presents a new social network to allow the monitoring of the evolution of
individuals' health status and diagnostic deficiencies, difficulties or barriers
in rehabilitation. The last paper reports on teenage patients' perception on
privacy and social media. CONCLUSION: Selected papers not only show the value of
using social media in the medical field but how to use these media to detect
emergent diseases or risks, inform patients, promote disease prevention, and
follow patients' opinion on healthcare resources.
PMID- 25123744
TI - EHR Big Data Deep Phenotyping. Contribution of the IMIA Genomic Medicine Working
Group.
AB - OBJECTIVES: Given the quickening speed of discovery of variant disease drivers
from combined patient genotype and phenotype data, the objective is to provide
methodology using big data technology to support the definition of deep
phenotypes in medical records. METHODS: As the vast stores of genomic information
increase with next generation sequencing, the importance of deep phenotyping
increases. The growth of genomic data and adoption of Electronic Health Records
(EHR) in medicine provides a unique opportunity to integrate phenotype and
genotype data into medical records. The method by which collections of clinical
findings and other health related data are leveraged to form meaningful
phenotypes is an active area of research. Longitudinal data stored in EHRs
provide a wealth of information that can be used to construct phenotypes of
patients. We focus on a practical problem around data integration for deep
phenotype identification within EHR data. The use of big data approaches are
described that enable scalable markup of EHR events that can be used for semantic
and temporal similarity analysis to support the identification of phenotype and
genotype relationships. CONCLUSIONS: Stead and colleagues' 2005 concept of using
light standards to increase the productivity of software systems by riding on the
wave of hardware/processing power is described as a harbinger for designing
future healthcare systems. The big data solution, using flexible markup, provides
a route to improved utilization of processing power for organizing patient
records in genotype and phenotype research.
PMID- 25123745
TI - Managing large-scale genomic datasets and translation into clinical practice.
AB - OBJECTIVE: To summarize excellent current research in the field of Bioinformatics
and Translational Informatics with application in the health domain. METHOD: We
provide a synopsis of the articles selected for the IMIA Yearbook 2014, from
which we attempt to derive a synthetic overview of current and future activities
in the field. A first step of selection was performed by querying MEDLINE with a
list of MeSH descriptors completed by a list of terms adapted to the section.
Each section editor evaluated independently the set of 1,851 articles and 15
articles were retained for peer-review. RESULTS: The selection and evaluation
process of this Yearbook's section on Bioinformatics and Translational
Informatics yielded three excellent articles regarding data management and genome
medicine. In the first article, the authors present VEST (Variant Effect Scoring
Tool) which is a supervised machine learning tool for prioritizing variants found
in exome sequencing projects that are more likely involved in human Mendelian
diseases. In the second article, the authors show how to infer surnames of male
individuals by crossing anonymous publicly available genomic data from the Y
chromosome and public genealogy data banks. The third article presents a
statistical framework called iCluster+ that can perform pattern discovery in
integrated cancer genomic data. This framework was able to determine different
tumor subtypes in colon cancer. CONCLUSIONS: The current research activities
still attest the continuous convergence of Bioinformatics and Medical
Informatics, with a focus this year on large-scale biological, genomic, and
Electronic Health Records data. Indeed, there is a need for powerful tools for
managing and interpreting complex data, but also a need for user-friendly tools
developed for the clinicians in their daily practice. All the recent research and
development efforts are contributing to the challenge of impacting clinically the
results and even going towards a personalized medicine in the near future.
PMID- 25123747
TI - Information technology for clinical, translational and comparative effectiveness
research. Findings from the section clinical research informatics.
AB - OBJECTIVE: To select and summarize key contributions to current research in the
field of Clinical Research Informatics (CRI). METHOD: A bibliographic search
using a combination of MeSH and free terms search over PubMed was performed
followed by a blinded review. RESULTS: The review process resulted in the
selection of four papers illustrating various aspects of current research efforts
in the area of CRI. The first paper tackles the challenge of extracting accurate
phenotypes from Electronic Healthcare Records (EHRs). Privacy protection within
shared de-identified, patient-level research databases is the focus of the second
selected paper. Two other papers exemplify the growing role of formal
representation of clinical data - in metadata repositories - and knowledge - in
ontologies - for supporting the process of reusing data for clinical research.
CONCLUSIONS: The selected articles demonstrate how concrete platforms are
currently achieving interoperability across clinical research and care domains
and have reached the evaluation phase. When EHRs linked to genetic data have the
potential to shift the research focus from research driven patient recruitment to
phenotyping in large population, a key issue is to lower patient re
identification risks for biomedical research databases. Current research
illustrates the potential of knowledge engineering to support, in the coming
years, the scientific lifecycle of clinical research.
PMID- 25123748
TI - Cardiovascular disease: the leap towards translational and clinical proteomics.
PMID- 25123749
TI - Prof. Michael (Mike) J. Dunn--paying forward.
PMID- 25123746
TI - Clinical research informatics and electronic health record data.
AB - OBJECTIVES: The goal of this survey is to discuss the impact of the growing
availability of electronic health record (EHR) data on the evolving field of
Clinical Research Informatics (CRI), which is the union of biomedical research
and informatics. RESULTS: Major challenges for the use of EHR-derived data for
research include the lack of standard methods for ensuring that data quality,
completeness, and provenance are sufficient to assess the appropriateness of its
use for research. Areas that need continued emphasis include methods for
integrating data from heterogeneous sources, guidelines (including explicit
phenotype definitions) for using these data in both pragmatic clinical trials and
observational investigations, strong data governance to better understand and
control quality of enterprise data, and promotion of national standards for
representing and using clinical data. CONCLUSIONS: The use of EHR data has become
a priority in CRI. Awareness of underlying clinical data collection processes
will be essential in order to leverage these data for clinical research and
patient care, and will require multi-disciplinary teams representing clinical
research, informatics, and healthcare operations. Considerations for the use of
EHR data provide a starting point for practical applications and a CRI research
agenda, which will be facilitated by CRI's key role in the infrastructure of a
learning healthcare system.
PMID- 25123743
TI - Surveying Recent Themes in Translational Bioinformatics: Big Data in EHRs, Omics
for Drugs, and Personal Genomics.
AB - OBJECTIVE: To provide a survey of recent progress in the use of large-scale
biologic data to impact clinical care, and the impact the reuse of electronic
health record data has made in genomic discovery. METHOD: Survey of key themes in
translational bioinformatics, primarily from 2012 and 2013. RESULT: This survey
focuses on four major themes: the growing use of Electronic Health Records (EHRs)
as a source for genomic discovery, adoption of genomics and pharmacogenomics in
clinical practice, the possible use of genomic technologies for drug repurposing,
and the use of personal genomics to guide care. CONCLUSION: Reuse of abundant
clinical data for research is speeding discovery, and implementation of genomic
data into clinical medicine is impacting care with new classes of data rarely
used previously in medicine.
PMID- 25123754
TI - Reply to magnetic resonance imaging-based diagnosis of progressive multifocal
leukoencephalopathy in a patient with non-Hodgkin lymphoma after therapy with
cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab.
PMID- 25123753
TI - The neuroprotective potential of sinapic acid in the 6-hydroxydopamine-induced
hemi-parkinsonian rat.
AB - Parkinson's disease (PD) is a neurodegenerative movement disorder due to
selective loss of dopaminergic neurons of mesencephalic substantia nigra pars
compacta (SNC) with debilitating motor symptoms. Current treatments for PD afford
symptomatic relief with no prevention of disease progression. Due to the
antioxidant and neuroprotective potential of sinapic acid, this study was
conducted to evaluate whether this agent could be of benefit in an experimental
model of early PD in rat. Unilateral intrastriatal 6-hydroxydopamine (6-OHDA)
lesioned rats were pretreated p.o. with sinapic acid at doses of 10 or 20 mg/kg.
One week after surgery, apomorphine caused significant contralateral rotations, a
significant reduction in the number of Nissl-stained and tyrosine hydroxylase
(TH)-positive neurons and a significant increase of iron reactivity on the left
side of SNC. Meanwhile, malondialdehyde (MDA) and nitrite levels in midbrain
homogenate significantly increased and activity of superoxide dismutase (SOD)
significantly reduced in the 6-OHDA-lesioned group. In addition, sinapic acid at
a dose of 20 mg/kg significantly improved turning behavior, prevented loss of SNC
dopaminergic neurons, lowered iron reactivity, and attenuated level of MDA and
nitrite. These results indicate the neuroprotective potential of sinapic acid
against 6-OHDA neurotoxicity that is partially due to the attenuation of
oxidative stress and possibly lowering nigral iron level.
PMID- 25123758
TI - Implant therapy: 40 years of experience.
AB - Implant placement has become a well-established and highly successful therapy in
the rehabilitation of partially and fully edentulous patients. The 'original'
treatment protocol, which aimed to demonstrate implant 'biocompatibility' and the
achievement of osseointegration, has evolved over the past 40 years into a
broader treatment approach in which the esthetic and patient-related objectives
have become the main focus. This volume of Periodontology 2000 summarizes, via
narrative reviews, the advantages and disadvantages of this evolution in
implantology and offers recommendations on where and when to apply the new
therapeutic protocols, without jeopardizing the outcome for the patient. It also
discusses current treatments of the most common implant-associated complications.
Many of the implant innovations and new therapeutic protocols are supported by
evidence-based knowledge and have provided clear benefits for both the patient
and the clinician.
PMID- 25123756
TI - Comment on 'Genetic evidence and new morphometric data as essential tools to
identify the Patagonian seahorse Hippocampus patagonicus (Pisces, Syngnathidae)
by Gonzalez et al. (2014)'.
PMID- 25123757
TI - Genotypic alteration and competitive nodulation of Mesorhizobium muleiense
against exotic chickpea rhizobia in alkaline soils.
AB - Mesorhizobium muleiense, Mesorhizobium mediterraneum and Mesorhizobium ciceri are
chickpea (Cicer arietinum L.) rhizobia that share a high similarity of the
symbiotic genes nodC and nifH, but they have different geographic distributions.
M. muleiense has been isolated and found only in alkaline soils of Xinjiang,
China, whereas the other two strains have been found in the Mediterranean and
India. To investigate the species stability of M. muleiense during natural
evolution and its capability of competitive nodulation against the other two
exotic species, re-sampling of nodules in the field and competition experiments
between the three species were conducted. The results showed that the predominant
microsymbiont associated with chickpea grown in Xinjiang was still M. muleiense,
but the predominant genotypes of M. muleiense had changed significantly during
the four years since a previous survey. The data also showed that M.
mediterraneum and M. ciceri were more competitive than the residential strain of
M. muleiense CCBAU 83963(T) in sterilized vermiculite or soils from Xinjiang.
However, in non-sterilized soils, M. muleiense was the predominant nodule
occupier. These results indicated that natural or adapting evolution of M.
muleiense was occurring in fields subjected to changing environmental factors. In
addition, the biogeography and symbiotic associations of rhizobia with their host
legumes were also influenced by biological factors in the soil, such as
indigenous rhizobia and other organisms.
PMID- 25123755
TI - The degree of retinopathy is equally predictive for renal and macrovascular
outcomes in the ACCORD Trial.
AB - AIMS: Diabetic retinopathy (DR) is associated with a higher risk of renal and
cardiovascular events. We sought to compare the risk for renal versus
cardiovascular (CV) outcomes, stratified by retinopathy severity. METHODS: ACCORD
was a randomized trial of people with type 2 diabetes, at high-risk for CV
disease. A subgroup (n=3,369 from 71 clinics) had stereoscopic fundus photographs
graded centrally. Participants were stratified at baseline to moderate/severe DR
or no/mild DR and were monitored for renal and CV outcomes at follow-up visits
over 4 years. The composite renal outcome was composed of serum creatinine
doubling, macroalbuminuria, or end-stage renal disease. The composite CV outcome
was the ACCORD trial primary outcome. Competing risk techniques were used to
estimate the relative risk (RR) of renal versus CV composite outcomes within each
DR stratum. RESULTS: The hazards ratio for doubling of serum creatinine and
incident CV event in the moderate/severe DR versus no/mild DR strata were: 2.31
(95% CI: 1.25-4.26) and 1.98 (95% CI: 1.49-2.62), respectively. The RR of the two
composite outcomes was highly similar in the no/mild DR stratum (adjusted RR at 4
years for CV versus renal events=0.96, 95% CI: 0.72-1.28) and the moderate/severe
DR stratum (adjusted RR=0.92, 95% CI: 0.64-1.31). CONCLUSIONS: Thus, in people
with type 2 diabetes at high risk for cardiovascular disease, incident CV versus
renal events was similar, irrespective of the severity of the DR. Further
evaluation of the specificity of DR for microvascular versus macrovascular events
in other populations is warranted.
PMID- 25123759
TI - Horizontal bone augmentation by means of guided bone regeneration.
AB - The development of bone augmentation procedures has allowed placement of dental
implants into jaw bone areas lacking an amount of bone sufficient for standard
implant placement. Thus, the indications for implants have broadened to include
jaw regions with bone defects and those with a bone anatomy that is unfavorable
for implant anchorage. Of the different techniques, the best documented and the
most widely used method to augment bone in localized alveolar defects is guided
bone regeneration. A large body of evidence has demonstrated the successful use
of guided bone regeneration to regenerate missing bone at implant sites with
insufficient bone volume and the long-term success of implants placed
simultaneously with, or after, guided bone regeneration. However, the influence
of guided bone regeneration on implant survival and success rates, and the long
term stability of the augmented bone, remain unknown. Many of the materials and
techniques currently available for bone regeneration of alveolar ridge defects
were developed many years ago. Recently, various new materials and techniques
have been introduced. Many of them have, however, not been sufficiently
documented in clinical studies. The aim of this review was to present the
scientific basis of guided bone regeneration and the accepted clinical
procedures. A classification of bone defects has been presented, aiming at
simplifying the decision-making process regarding the choice of strategy for bone
augmentation. Finally, an outlook into actual research and the possible future
options related to bone augmentation has been provided.
PMID- 25123760
TI - Zygomatic implants: indications, techniques and outcomes, and the zygomatic
success code.
AB - The zygoma implant has been an effective option in the management of the atrophic
edentulous maxilla as well as for maxillectomy defects. Branemark introduced the
zygoma implant not only as a solution to obtain posterior maxillary anchorage but
also to expedite the rehabilitation process. The zygoma implant is a therapeutic
option that deserves consideration in the treatment-planting process. This paper
reviews the indications for zygoma implants and the surgical and prosthetic
techniques (including new developments) and also reports on the clinical outcome
of the zygomatic anatomy-guided approach. An overview of conventional grafting
procedures is also included. Finally, a Zygoma Success Code, describing specific
criteria to score the success of rehabilitation anchored on zygomatic implants,
is proposed.
PMID- 25123762
TI - Short implant in limited bone volume.
AB - Rehabilitation of severely resorbed jaws with dental implants remains a surgical
and prosthetic challenge for clinicians. The purpose of this review was to
evaluate the available data on short-length implants and discuss their
indications and limitations in daily clinical practice. A structured review of
MEDLINE and a manual search were conducted. Thirty-two case series devoted to
short-length implants, 14 reviews and 3 randomized controlled trials were
identified. Of this group of papers, we can conclude that short-length implants
can be successfully used to support single and multiple fixed reconstructions in
posterior atrophied jaws, even in those with increased crown-to-implant ratios.
The use of short-length implants allows treatment of patients who are unable to
undergo complex surgical techniques for medical, anatomic or financial reasons.
Moreover, the use of short-length implants in daily clinical practice reduces the
need for complex surgeries, thus reducing morbidity, cost and treatment time. The
use of short implants promotes the new concept of stress-minimizing surgery,
allowing the surgeon to focus more on the correct three-dimensional positioning
of the implant.
PMID- 25123763
TI - Critical buccal bone dimensions along implants.
AB - The buccal bone plate is a component of the alveolar process tightly related to
the tooth it supports. A plethora of physiological and pathological events can
induce its remodeling. Understanding this remodeling process and its extent is of
major importance for the practitioner as it can affect the functional and
esthetic outcome of implant surgery at the involved sites. Bone remodeling and
resorption of the buccal bone plate are inevitable after tooth loss or
extraction. To limit resorption, several ridge-preservation techniques of varying
efficacy have been described. Bone resorption is equally found to occur upon
implant placement and is thought to be a result of the surgical trauma inflicted
as well as an adaptation process of the tissues to the new foreign body. Because
of the implications of bone resorption on the soft-tissue levels and the general
esthetic outcome, it is of primary importance for the practitioner to be able to
evaluate the hard tissues and the inherent resorption risks in an effort to
optimize the treatment strategies. Based on limited short-term data, the present
general opinion advises the need for a 2-mm-thick buccal bone plate in order to
avoid vertical bone resorption.
PMID- 25123761
TI - Sinus floor elevation utilizing the transalveolar approach.
AB - A transalveolar approach for sinus floor elevation with subsequent placement of
dental implants was first suggested by Tatum in 1986. In 1994, Summers described
a different transalveolar approach using a set of tapered osteotomes with
increasing diameters. The transalveolar approach of sinus floor elevation, also
referred to as 'osteotome sinus floor elevation', the 'Summers technique' or the
'Crestal approach', may be considered as being more conservative and less
invasive than the conventional lateral window approach. This is reflected by the
fact that more than nine out of 10 patients who experienced the surgical
procedure would be willing to undergo it again. The main indication for
transalveolar sinus floor elevation is reduced residual bone height, which does
not allow standard implant placement. Contraindications for transalveolar sinus
floor elevation may be intra-oral, local or medical. The surgical approach
utilized over the last two decades is the technique described by Summers, with or
without minor modifications. The surgical care after implant placement using the
osteotome technique is similar to the surgical care after standard implant
placement. The patients are usually advised to take antibiotic prophylaxis and to
utilize antiseptic rinses. The main complications reported after performing a
transalveolar sinus floor elevation were perforation of the Schneiderian membrane
in 3.8% of patients and postoperative infections in 0.8% of patients. Other
complications reported were postoperative hemorrhage, nasal bleeding, blocked
nose, hematomas and benign paroxysmal positional vertigo. Whether it is necessary
to use grafting material to maintain space for new bone formation after elevating
the sinus membrane utilizing the osteotome technique is still controversial.
Positive outcomes have been reported with and without using grafting material. A
prospective study, evaluating both approaches, concluded that significantly more
bone gain was seen when grafting material was used (4.1 mm mean bone gain
compared with 1.7 mm when no grafting material was utilized). In a systematic
review, including 19 studies reporting on 4388 implants inserted using the
transalveolar sinus floor elevation technique, the 3-year implant survival rate
was 92.8% (95% confidence interval: 87.4-96.0%). Furthermore, a subject-based
analysis of the same material revealed an annual failure rate of 3.7%. Hence, one
in 10 subjects experienced implant loss over 3 years. Several of the included
studies demonstrated that transalveolar sinus floor elevation was most
predictable when the residual alveolar bone height was >= 5 mm and the sinus
floor anatomy was relatively flat.
PMID- 25123764
TI - Critical soft-tissue dimensions with dental implants and treatment concepts.
AB - Dental implants have proven to be a successful treatment option in fully and
partially edentulous patients, rendering long-term functional and esthetic
outcomes. Various factors are crucial for predictable long-term peri-implant
tissue stability, including the biologic width; the papilla height and the
mucosal soft-tissue level; the amounts of soft-tissue volume and keratinized
tissue; and the biotype of the mucosa. The biotype of the mucosa is congenitally
set, whereas many other parameters can, to some extent, be influenced by the
treatment itself. Clinically, the choice of the dental implant and the position
in a vertical and horizontal direction can substantially influence the
establishment of the biologic width and subsequently the location of the buccal
mucosa and the papilla height. Current treatment concepts predominantly focus on
providing optimized peri-implant soft-tissue conditions before the start of the
prosthetic phase and insertion of the final reconstruction. These include refined
surgical techniques and the use of materials from autogenous and xenogenic
origins to augment soft-tissue volume and keratinized tissue around dental
implants, thereby mimicking the appearance of natural teeth.
PMID- 25123765
TI - Implant-assisted complete prostheses.
AB - The current review was undertaken to obtain a better understanding of the
knowledge base of implant-assisted complete dental prostheses (fixed and
removable) in the treatment of the completely edentulous maxilla or mandible.
Indications, advantages and disadvantages, complications and maintenance issues,
as well as the cost-effectiveness of both treatments, are discussed to help
clinicians in their therapeutic decision-making. In summary, when indicated and
depending on the patients' needs, both removable and fixed implant-assisted
prostheses are highly safe, reliable and satisfactory treatment modalities for
the rehabilitation of edentulous jaws. Careful and precise treatment planning is
highly recommended to assist the clinician in preventing potential prosthetic
failures. The review also reveals that there is still a need for data, generated
using robust research methods, on some patient-based and clinical outcomes.
PMID- 25123766
TI - Immediate implants at fresh extraction sockets: from myth to reality.
AB - In recent years, immediate implant placement has become a common clinical
therapeutic protocol representing an alternative to the classical delayed
surgical protocol of implant placement. This protocol, however, has not been
fully validated, either in terms of fully understanding the influence of implant
placement on the socket-healing process or on the clinical outcomes. This
narrative review evaluates the different experimental studies in humans and
animals assessing the bone-healing dynamics of the socket after tooth extraction
and the dimensional changes occurring at the socket bone walls. These
experimental studies describe, in detail, the hard- and soft-tissue healing of
implants placed into fresh extraction sockets, demonstrating that marked
morphological changes of the alveolar ridge will occur, independently of the
implant installation, thus demonstrating that postextraction bone loss is an
inevitable biological process. This evidence has also been corroborated in
clinical studies in humans, demonstrating the risk of significant peri-implant
tissue loss, mainly in the areas of high esthetic demand. There is a lack of long
term evidence on the impact of this protocol on the preservation of the peri
implant tissues. In conclusion, despite the obvious advantages of this surgical
protocol, it also has limitations and is more technically demanding than placing
an implant into a healed crest. When selecting this protocol, clinicians should
always consider: (a) the gingival biotype of the patient; (b) the thickness and
integrity of the socket bony walls; (c) the implant selection as well as the
adequate vertical and horizontal position of the implant; and (d) the ideal
patient (a nonsmoker with good plaque control).
PMID- 25123767
TI - Immediate loading in partially and completely edentulous jaws: a review of the
literature with clinical guidelines.
AB - The introduction of immediate loading was a paradigm shift in implant dentistry
as it was previously believed that an unloaded period was essential for bone
healing in order to promote osseointegration. However, this belief could not be
confirmed by clinical studies or by human histology. Hitherto, numerous reports
have been published on immediate loading in various indications. An important
factor for success is primary implant stability. The latter can be improved by
adapting drilling protocols to enhance lateral compression of the bone and by
using tapered implant designs with apical thread fixation. To some extent, the
use of implants with a microrough surface and rigid splinting may compensate for
suboptimal stability. It is important to avoid fracture of the provisional
restoration at all times as this may result in local overloading and implant
failure. Also, unevenly distributed occlusal contacts may contribute to failure
and therefore occlusion ought to be evaluated at every occasion, especially
during the early phase of healing. Taking these aspects into account, immediate
loading in the fully edentulous mandible by means of an overdenture has been
shown to be predictable in terms of implant survival (94.4-100%). However, the
procedure may result in additional costs as a result of the need for repeated
relining. In addition, the scientific basis for this treatment concept in the
maxilla is very scarce. Immediate loading in the fully edentulous jaw by means of
a fixed prosthesis is a well-documented treatment concept. In the mandible, three
implants have been shown to be insufficient, given the failure rate of up to 10%.
With at least four implants a failure rate of 0-3.3% may be expected. In the
maxilla, four to six implants could be too limited, given the failure rate up to
7.2%. Increasing the number of implants may reduce implant failure to 3.3%.
Provisional fixed prostheses are particularly prone to fracture in the maxilla
and hence reinforcement is warranted. Immediately loaded single implants have
lower survival rates, of 85.7-100%, with no clear impact of occlusal contact. In
fact, a meta-analysis demonstrated a five times higher risk of failure for
immediately loaded single implants when compared with delayed loading. No study
showed superior soft-tissue preservation or esthetics following immediate loading
of single implants compared with other loading protocols. However, this finding
may not imply that a provisional implant crown becomes redundant when soft-tissue
conditioning is deemed necessary. Taking into account earlier factors for
success, immediate loading in the partially edentulous jaw by means of a fixed
prosthesis seems predictable in terms of implant survival (95.5-100%). However,
there are no studies with data on soft-tissue parameters, esthetic aspects or
patient-centered outcomes, and the available studies mainly relate to the load
carrying part of the dentition. Clinical studies focusing on these aspects of
treatment outcome are clearly needed. High patient satisfaction is the most
important advantage of immediate loading, especially during the early healing
phase. In this context, one should also realize that studies have revealed
comparable patient satisfaction in patients following delayed loading once their
prosthesis is in place. In the decision-making process, this aspect should be
properly discussed with the patient along with other advantages and disadvantages
of immediate loading.
PMID- 25123768
TI - Neurovascular disturbances after implant surgery.
AB - With a steadily increasing impact of oral implant placement in daily practice,
the number of reported surgical complications has also been growing. Recent
studies reveal significant variation in the occurrence and morphology of
neurovascular canal structures in the jaw bone. All those structures contain a
neurovascular bundle, the diameter of which may be large enough to cause
clinically significant damage. Therefore, it has become obvious that presurgical
radiographic planning of jaw-bone surgery should pay attention to the
neurovascular structures and their likely variations, in addition to examining
many other factors, such as jaw-bone morphology and volume, bone trabecular
structure and the absence of bone or tooth pathology. A critical review is
accomplished to explore the potential risks for neurovascular complications after
implant placement, with evidence derived from histologic, anatomic, clinical and
radiologic studies. In this respect, cross-sectional imaging can often be
advocated, as it is obvious that the inherent three-dimensional nature of jaw
bone anatomy may clearly benefit from a detailed spatial image analysis. Although
this could initially be realized by conventional computed tomography, in current
practice, dentomaxillofacial cone beam computed tomography might be used, as it
offers high-quality images at low radiation dose levels and costs.
PMID- 25123769
TI - Dental cone beam computed tomography: justification for use in planning oral
implant placement.
AB - Intra-oral and panoramic radiographs are most frequently used in oral health
care. Yet, the inherent nature of jaws and teeth renders three-dimensional
diagnosis essential, especially in relation to oral surgery. Nowadays, this can
be accomplished by dental cone beam computed tomography, which provides high
quality images at low radiation doses and low costs. Nonetheless, the effective
dose ranges of cone beam computed tomography machines may easily vary from 10 to
1000 MUSv, this being equivalent to two to 200 panoramic radiographs, even for
similar presurgical indications. Moreover, the diagnostic image quality varies
massively among available machines and parameter settings. Apart from the
radiodiagnostic possibilities, dental cone beam computed tomography may offer a
vast therapeutic potential, including opportunities for surgical guidance and
further prosthetic rehabilitation via computer-aided design/computer-aided
manufacturing solutions. These additional options may definitely explain part of
the success of cone beam computed tomography for oral implant placement. In
conclusion, dental cone beam computed tomography imaging could be justified for
oral implant-related diagnosis, planning and transfer to surgical and further
prosthetic treatment, but guidelines for justification and cone beam computed
tomography optimization remain mandatory.
PMID- 25123770
TI - Different techniques of static/dynamic guided implant surgery: modalities and
indications.
AB - For computer-guided surgery a static surgical guide is used that transfers the
virtual implant position from computerized tomographic data to the surgical site.
These guides are produced by computer-aided design/computer-assisted manufacture
technology, such as stereolithography, or manually in a dental laboratory (using
mechanical positioning devices or drilling machines). With computer-navigated
surgery the position of the instruments in the surgical area is constantly
displayed on a screen with a three-dimensional image of the patient. In this way,
the system allows real-time transfer of the preoperative planning and visual
feedback on the screen. A workflow of the different systems is presented in this
review.
PMID- 25123771
TI - Guided surgery: accuracy and efficacy.
AB - Different computer-assisted implant-placement procedures are currently available.
These differ in software, template manufacture, guiding device, stabilization and
fixation. The literature seems to indicate that one has to accept a certain
inaccuracy of +/-2.0 mm, which seems large initially but is clearly smaller than
for nonguided surgery. A reduction of accuracy to below 0.5 mm seems extremely
difficult. A common shortcoming identified in the studies included in this review
is inconsistency in how clinical data and outcome variables are reported. Another
limitation is the small number of comparative clinical studies. In order to find
the best guiding system or the most important parameters for optimal accuracy,
more randomized clinical trials are necessary. Information on cost-effectiveness
and patient-centered evaluations (i.e. questionnaires and interviews) must also
be included.
PMID- 25123772
TI - Etiology and treatment of periapical lesions around dental implants.
AB - The widespread use of oral implants in recent years has resulted in various types
of complications. One of those complications is the periapical implant lesion.
Different factors have been proposed to play a role in the development and
emergence of a periapical implant lesion. To date, there is no consensus on the
etiology and therefore periapical lesions around dental implants are considered
to have a multifactorial etiology. The diagnosis of an implant periapical lesion
should be based on both clinical and radiological findings. Additionally, in
order to apply the best treatment strategy the evolution of the lesion should be
taken into account. The treatment of this kind of lesion, however, is still
empiric. Data, primarily from case reports, seem to indicate that the removal of
all granulation tissue is a first step to arrest the progression of the bone
destruction. The removal of the apical part of the implant seems a valuable
treatment strategy.
PMID- 25123773
TI - Management of peri-implant mucositis and peri-implantitis.
AB - Peri-implant diseases are defined as inflammatory lesions of the surrounding peri
implant tissues and include peri-implant mucositis (an inflammatory lesion
limited to the surrounding mucosa of an implant) and peri-implantitis (an
inflammatory lesion of the mucosa that affects the supporting bone with resulting
loss of osseointegration). This review aims to describe the different approaches
to manage both entities and to provide a critical evaluation of the evidence
available on their efficacy. Therapy of peri-implant mucositis and nonsurgical
therapy of peri-implantitis usually involve mechanical debridement of the implant
surface using curettes, ultrasonic devices, air-abrasive devices or lasers, with
or without the adjunctive use of local antibiotics or antiseptics. The efficacy
of these therapies has been demonstrated for mucositis: controlled clinical
trials show an improvement in clinical parameters, especially in bleeding on
probing. For peri-implantitis, the results are limited, especially in terms of
probing pocket-depth reduction. Surgical therapy of peri-implantitis is indicated
when nonsurgical therapy fails to control the inflammatory changes. Selection of
the surgical technique should be based on the characteristics of the peri-implant
lesion. In the presence of deep circumferential and intrabony defects, surgical
interventions should aim to provide thorough debridement, implant-surface
decontamination and defect reconstruction. In the presence of defects without
clear bony walls or with a predominant suprabony component, the aim of the
surgical intervention should be the thorough debridement and the repositioning of
the marginal mucosa to enable the patient to perform effective oral-hygiene
practices, although this aim may compromise the esthetic result of the implant
supported restoration.
PMID- 25123774
TI - Optimizing multiple-choice tests as tools for learning.
AB - Answering multiple-choice questions with competitive alternatives can enhance
performance on a later test, not only on questions about the information
previously tested, but also on questions about related information not previously
tested-in particular, on questions about information pertaining to the previously
incorrect alternatives. In the present research, we assessed a possible
explanation for this pattern: When multiple-choice questions contain competitive
incorrect alternatives, test-takers are led to retrieve previously studied
information pertaining to all of the alternatives in order to discriminate among
them and select an answer, with such processing strengthening later access to
information associated with both the correct and incorrect alternatives.
Supporting this hypothesis, we found enhanced performance on a later cued-recall
test for previously nontested questions when their answers had previously
appeared as competitive incorrect alternatives in the initial multiple-choice
test, but not when they had previously appeared as noncompetitive alternatives.
Importantly, however, competitive alternatives were not more likely than
noncompetitive alternatives to be intruded as incorrect responses, indicating
that a general increased accessibility for previously presented incorrect
alternatives could not be the explanation for these results. The present
findings, replicated across two experiments (one in which corrective feedback was
provided during the initial multiple-choice testing, and one in which it was
not), thus strongly suggest that competitive multiple-choice questions can
trigger beneficial retrieval processes for both tested and related information,
and the results have implications for the effective use of multiple-choice tests
as tools for learning.
PMID- 25123775
TI - Israel-Gaza conflict.
PMID- 25123776
TI - Israel-Gaza conflict.
PMID- 25123777
TI - Letter in support of Richard Horton.
PMID- 25123778
TI - Risk factors and early origins of chronic obstructive pulmonary disease.
AB - Chronic obstructive pulmonary disease is mainly a smoking-related disorder and
affects millions of people worldwide, with a large effect on individual patients
and society as a whole. Although the disease becomes clinically apparent around
the age of 40-50 years, its origins can begin very early in life. Different risk
factors in very early life--ie, in utero and during early childhood--drive the
development of clinically apparent chronic obstructive pulmonary disease in later
life. In discussions of which risk factors drive chronic obstructive pulmonary
disease, it is important to realise that the disease is very heterogeneous and at
present is largely diagnosed by lung function only. In this Review, we will
discuss the evidence for risk factors for the various phenotypes of chronic
obstructive pulmonary disease during different stages of life.
PMID- 25123779
TI - Concordance and discordance in patient and provider perceptions of dizziness.
AB - PURPOSE: The purpose of the present investigation was to determine whether there
are significant differences in patient/healthcare provider perceptions of
patient's dizziness severity, dizziness disability/handicap, anxiety, and signs
of autonomic system activation. MATERIALS AND METHODS: This was a prospective
investigation of 30 patient-provider dyads drawn as a sample of convenience from
an otology clinic in a large, tertiary care, medical center. Patients completed
both the Dizziness Handicap Inventory (DHI) and the Vestibular Symptom Scale
(VSS) prior to vestibular function testing. Providers were instructed to complete
the same measures following the patient's clinic visit from what they estimated
was the patient's point of view. The two measures were analyzed for concordance
and discordance. RESULTS: Patient/provider differences in DHI and VSS vertigo
subscale scores were not significantly different. However, difference scores on
the VSS anxiety/autonomic subscale indicated that providers significantly under
estimated patient anxiety and symptoms of autonomic system activation.
CONCLUSIONS: The results suggest that providers may be missing information
pertinent to the role anxiety and autonomic system activation may play in patient
visits for complaints of dizziness. We suggest that this problem can be mitigated
by administrating to patients prior to their clinic visit a standardized measure
that quantifies patient self-report dizziness, vertigo, anxiety and autonomic
system arousal. Patterns of response by patients on these measures can enable
providers to diagnose correctly dizziness disorders that are rooted in clinically
significant anxiety either related to, or unrelated to, a history of vestibular
system impairment.
PMID- 25123780
TI - Pediatric mandibular reconstruction following resection of oral squamous cell
carcinoma: a case report.
AB - PURPOSE: Squamous cell carcinoma is a common entity among adult head and neck
cancer patients, with many requiring reconstruction post resection. Conversely,
this entity is rare among children with major reconstruction even more unique.
This case and the concomitant review of literature highlight the intricacies of
pediatric facial reconstruction. METHODS: The case described is of a 6-year-old
African-American boy with poor dentition and a painful, 1.5 cm epiphytic lesion
on the alveolar ridge of the left mandible. Incisional biopsy and computerized
tomography were employed to obtain diagnosis and extent of disease. Surgical
resection and reconstruction followed. RESULTS: Incisional biopsy confirmed the
diagnosis of squamous cell carcinoma. Maxillofacial computerized tomography
confirmed the extent of the mandibular lesion. After interdisciplinary discussion
and weighing options with the family, a segmental mandibulectomy, neck
dissection, and right fibula free flap reconstruction with titanium 2.0 mm metal
plate fixation was performed. Re-examination post-operatively showed complete
coverage of the defect and the ability to restore excised dentition. CONCLUSION:
Squamous cell carcinoma within the pediatric population occurs less often than
sarcomas, but may necessitate major reconstruction. Without rigid reconstruction,
contracture may result. The current consensus favors microvascular bone
reconstruction. However, a lack of consensus exists regarding the timing of
dental rehabilitation.
PMID- 25123781
TI - The AGREE Enterprise: a decade of advancing clinical practice guidelines.
AB - BACKGROUND: The original AGREE (Appraisal of Guidelines for REsearch and
Evaluation) Instrument was published in 2003, and its revision, the AGREE II, in
2009. Together, they filled an important gap in the guideline and quality of care
fields. Ten years later, the AGREE Enterprise reflects on a trajectory of
projects and international collaboration that have contributed to advancing the
science and quality of practice guidelines and the uptake of AGREE/AGREE II.
FINDINGS: The AGREE Enterprise has undertaken activities to improve the tool and
to develop resources to support its use. Since 2003, the uptake and adoption of
AGREE by the international community has been swift and broad. A total of 33
language translations of the original AGREE Instrument and the current AGREE II
are available and were initiated by the international community. A recent scan of
the published literature identified over 600 articles that referenced the AGREE
tools. The AGREE tools have been widely received and applied, with several
organizations having incorporated the AGREE as part of their formal practice
guideline programs. Since its redevelopment in 2010, the AGREE Enterprise website
(www.agreetrust.org) continues to experience steady increases in visitors per
month and currently has over 10,000 registered users. CONCLUSIONS: The AGREE
Enterprise has contributed to the advancements of guidelines through research
activities and international participation by scientific and user communities. As
we enter a new decade, we look forward to ongoing collaborations and contributing
to further advancements to improve quality of care and health care systems.
PMID- 25123783
TI - An ab initio study of the thermoelectric enhancement potential in nano-grained
TiNiSn.
AB - Novel approaches for the development of highly efficient thermoelectric materials
capable of a direct conversion of heat into electricity, are being constantly
investigated. TiNiSn based half-Heusler alloys exhibit a high thermoelectric
potential for practical, renewable power generation applications. The main
challenge of further enhancement of the thermoelectric efficiency of these alloys
lies in the reduction of the associated high lattice thermal conductivity values
without adversely affecting the electronic transport properties. The current
manuscript theoretically investigates two possible routes for overcoming this
limitation in TiNiSn alloys. On the one hand, the influence of nano-grained
structure of TiNiSn on the electronic structure of the material is theoretically
demonstrated. On the other hand, the potential for thermal conductivity reduction
upon increasing the Ni fraction in the intermetallic TiNiSn compound via the
formation of metallic TiNi2Sn nanoparticles is also shown. Using the applied
approach, a useful route for optimizing both the electronic and thermal
properties of half-Heusler TiNiSn, for practical thermoelectric applications, is
demonstrated.
PMID- 25123782
TI - Differentiation of bland from neoplastic thrombus of the portal vein in patients
with hepatocellular carcinoma: application of susceptibility-weighted MR imaging.
AB - BACKGROUND: Neoplastic and bland portal vein thrombi (PVT) are both common in
patients with hepatocellular carcinoma (HCC). The correct discrimination of them
is essential for therapeutic strategies planning and survival predicting. The
current study aims to investigate the value of susceptibility-weighted imaging
(SWI) in differentiating bland from neoplastic PVT in HCC patients. METHODS: 20
HCC patients with bland PVT and 22 HCC patients with neoplastic PVT were imaged
with non-contrast SWI at 3.0 Tesla MRI. The signal intensity (SI) of the PVT and
HCC lesions in the same patients was compared on SW images. The phase values of
the PVT were compared between neoplastic and bland thrombi cohorts. Receiver
operator characteristics (ROC) analysis was conducted to evaluate the diagnostic
ability of the phase values for neoplastic and bland thrombi discrimination.
RESULTS: 20 of 22 neoplastic PVT were judged similar SI and 2 were judged lower
SI than their HCC. For 20 bland PVT, 19 were judged lower SI and 1 was judged
similar SI as their HCC (P<0.001). The average phase values (0.361 +/- 0.224) of
the bland PVT were significantly higher than those of the neoplastic PVT (-0.328
+/- 0.127, P<0.001). The AUC for phase values in differentiating bland from
neoplastic PVT was 0.989. The best cut-off value was -0.195, which gave a
sensitivity of 95% and a specificity of 95.5%. CONCLUSIONS: SW imaging appears to
be a promising new method for distinguishing neoplastic from bland PVT. The high
sensitivity and specificity suggest its high value in clinical practice.
PMID- 25123784
TI - Weight loss after participation in a national VA weight management program among
veterans with or without PTSD.
AB - OBJECTIVE: This evaluation compared the effectiveness of MOVE!, a U.S. Veterans
Health Administration (VHA) weight management program, among veterans with
posttraumatic stress disorder (PTSD), other mental conditions, or no mental
health diagnoses. METHODS: VHA administrative data from 2008 to 2012 were used to
estimate adjusted six- and 12-month weight change and >=5% weight loss among
20,819 veterans with "intense and sustained" MOVE! participation (14% of 148,963
MOVE! participants, regardless of mental health status). RESULTS: Compared with
veterans with no mental health diagnoses, veterans with PTSD lost significantly
less weight at six and 12 months (p<.05) and were less likely to lose >=5% body
weight at six months (OR=.89, p<.05). At six months, those with other mental
conditions lost significantly less weight than those with no mental health
diagnoses (p<.05). CONCLUSIONS: MOVE! may need adaptation to increase overall
engagement and enhance weight loss for veterans with mental conditions,
especially PTSD.
PMID- 25123785
TI - Morphological and thermodynamic comparison of the lesions created by 4 open
irrigated catheters in 2 experimental models.
AB - INTRODUCTION: New generation open-irrigated catheters aim to improve irrigation
efficiency. This may change lesion patterns, challenging operators. Indeed,
safety issues have recently arisen. We aimed to experimentally assess 4 open
irrigated catheters, comparing lesion size, safety, and heat transfer. METHODS:
The thigh lesion model was employed in 6 anesthetized pigs to assess the
morphology of perpendicular and tangential lesions (n = 140) created by the newer
catheters ThermoCool(r) SF, CoolFlexTM, and BlazerTM Open-Irrigated, and the
standard ThermoCool(r), at a constant power of 30 W (60 seconds). To evaluate the
propensity for deep-tissue overheating, a set of 120 applications were performed
at 50 W (180 seconds) comparing pop rates. Thermal assessment of the lesion
generation process (20 W, 60 seconds, n = 32) was performed with an infrared
camera on bovine ventricular tissue. RESULTS: At 30 W, the newer catheters showed
lower temperature readings compared with the ThermoCool(r). No major efficacy or
safety differences were found at tangential applications; however, at
perpendicular applications: (1) the SF at 17 mL/min better preserved the
superficial layers and focused its maximum thermal effect deeper, but at
recommended flow rates (8 mL/min) it generated the largest superficial lesions;
(2) CoolFlexTM created smaller lesions than SF and readily induced steam pops at
50 W without temperature control; and (3) no major differences were found
comparing BlazerTM Open-Irrigated and ThermoCool(r). CONCLUSIONS: The lower
temperature readings in the newer catheters make them more prone to deliver the
maximum programmed power. Under experimental conditions, the SF catheter focuses
its maximum effect deeper and the CoolFlexTM can be more prone to induce steam
pops at high power settings.
PMID- 25123786
TI - Stricter indications are recommended for fenestration surgery in intracranial
arachnoid cysts of children.
AB - PURPOSE: The indication of surgical treatment for intracranial arachnoid cysts
(ACs) is a controversial issue. In this study, we reviewed surgical outcomes of
intracranial ACs that were treated with endoscopic fenestration or microscopic
fenestration, which are currently standard practices for surgical treatment of
AC. In addition, we also evaluated the validity of current surgical indications.
METHODS: We analyzed pediatric patients under 18 years of age who underwent
surgical management for intracranial AC between January 2000 and December 2011.
Patients with a follow-up period of less than 1 year were excluded. A total of 75
patients were enrolled in this study. These patients were assessed by subjective
symptoms and by a clinician's objective evaluation. The radiological assessment
of AC after surgery was also evaluated. RESULTS: The median age of patients at
the initial operation was 5 years. The median follow-up period was 38 months. The
goal of surgery was achieved in 28% (21/75) of patients. The radiological
alteration of AC after initial fenestration surgery was diverse. The results of
the clinical and radiological assessments did not always coincide. A total of 35
complications occurred in 28 patients. Subdural fluid collection was the most
common unexpected radiological complication. CONCLUSIONS: Our study showed that
the fenestration procedure for AC produced unsatisfactory clinical improvements
compared to the relatively high complication rate. Therefore, surgical treatment
for AC should be strictly limited to patients who have symptoms directly related
to AC.
PMID- 25123788
TI - Effects of dispersant used for oil spill remediation on nitrogen cycling in
Louisiana coastal salt marsh soil.
AB - On April 20, 2010, the BP Deepwater Horizon (DWH) offshore oil platform
experienced an explosion which triggered the largest marine oil spill in US
history. Approximately 7.9 million liters of dispersant, Corexit EC9500A, was
used during the spill between May 15th and July 12th. Marsh soil samples were
collected from an unimpacted marsh site proximal to coastal areas that suffered
light to heavy oiling for a laboratory evaluation to determine the effect of
Corexit on the wetland soil microbial biomass as well as N-mineralization and
denitrification rates. Microbial biomass nitrogen (N) values were below detection
for the 1:10, 1:100 and 1:1000 Corexit:wet soil treatments. The potentially
mineralizable N (PMN) rate correlated with microbial biomass with significantly
lower rates for the 1:10 and 1:100 Corexit:wet soil additions. Potential
denitrification rates for Corexit:wet soil ratios after immediate dispersant
exposure were below detection for the 1:10 treatment, while the 1:100 was 7.6+/
2.7% of the control and the 1:1000 was 33+/-4.3% of the control. The 1:10000
treatment was not significantly different from the control. Denitrification rates
measured after 2 weeks exposure to the surfactant found the 1:10 treatment still
below detection limit and the 1:100 ratio was 12+/-2.6% of the control. Results
from this lab study suggest that chemical dispersants have the potential to
negatively affect the wetland soil microbial biomass and resultant microbial
activity. Consequences of exposure led to reductions in several important
microbial-regulated ecosystem services including water quality improvement
(denitrification) and ecosystem primary productivity (N-mineralization). Future
studies should investigate the longer-term impacts of dispersant exposure on the
microbial consortia to determine if microbial activity recovers over time.
PMID- 25123787
TI - Alternative polyadenylation regulates CELF1/CUGBP1 target transcripts following T
cell activation.
AB - Alternative polyadenylation (APA) is an evolutionarily conserved mechanism for
regulating gene expression. Transcript 3' end shortening through changes in
polyadenylation site usage occurs following T cell activation, but the
consequences of APA on gene expression are poorly understood. We previously
showed that GU-rich elements (GREs) found in the 3' untranslated regions of
select transcripts mediate rapid mRNA decay by recruiting the protein
CELF1/CUGBP1. Using a global RNA sequencing approach, we found that a network of
CELF1 target transcripts involved in cell division underwent preferential 3' end
shortening via APA following T cell activation, resulting in decreased inclusion
of CELF1 binding sites and increased transcript expression. We present a model
whereby CELF1 regulates APA site selection following T cell activation through
reversible binding to nearby GRE sequences. These findings provide insight into
the role of APA in controlling cellular proliferation during biological processes
such as development, oncogenesis and T cell activation.
PMID- 25123789
TI - Mangiferin treatment inhibits hepatic expression of acyl-coenzyme
A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive
rats: a link to amelioration of fatty liver.
AB - Mangiferin, a xanthone glucoside, and its associated traditional herbs have been
demonstrated to improve abnormalities of lipid metabolism. However, its
underlying mechanisms remain largely unclear. This study investigated the anti
steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat
(SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)
1. The results showed that co-administration of mangiferin (15 mg/kg, once daily,
by oral gavage) over 7 weeks dramatically diminished fructose-induced increases
in hepatic triglyceride content and Oil Red O-stained area in SHRs. However,
blood pressure, fructose and chow intakes, white adipose tissue weight and
metabolic parameters (plasma concentrations of glucose, insulin, triglyceride,
total cholesterol and non-esterified fatty acids) were unaffected by mangiferin
treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme
A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein
levels in the liver. In contrast, mangiferin treatment was without effect on
hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response
element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA
carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase
2, microsomal triglyceride transfer protein, peroxisome proliferator-activated
receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase.
Collectively, our results suggest that mangiferin treatment ameliorates fatty
liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final
step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may
occur independently of the hepatic signals associated with de novo fatty acid
synthesis and oxidation.
PMID- 25123790
TI - Tetrachloro-p-benzoquinone induces hepatic oxidative damage and inflammatory
response, but not apoptosis in mouse: the prevention of curcumin.
AB - This study investigated the protective effects of curcumin on tetrachloro-p
benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes
significant liver injury (the elevation of serum AST and ALT activities,
histopathological changes in liver section including centrilobular necrosis and
inflammatory cells), oxidative stress (the elevation of TBAR level and the
inhibition of SOD and catalase activities) and inflammation (up-regulation of
iNOS, COX-2, IL-1beta, IL-6, TNF-alpha and NF-kappaB). However, these changes
were alleviated upon pretreatment with curcumin. Interestingly, TCBQ has no
effect on caspase family genes or B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X
(Bax) protein expressions, which implied that TCBQ-induced hepatotoxicity is
independent of apoptosis. Moreover, curcumin was shown to induce phase II
detoxifying/antioxidant enzymes HO-1 and NQO1 through the activation of nuclear
factor erythroid-derived 2-like 2 (Nrf2). In summary, the protective mechanisms
of curcumin against TCBQ-induced hepatoxicity may be related to the attenuation
of oxidative stress, along with the inhibition of inflammatory response via the
activation of Nrf2 signaling.
PMID- 25123791
TI - Designed modulation of sex steroid signaling inhibits telomerase activity and
proliferation of human prostate cancer cells.
AB - The predominant estrogen-receptor (ER)-beta signaling in normal prostate is
countered by increased ER-alpha signaling in prostate cancer (CaP), which in
association with androgen-receptor (AR) signaling results in pathogenesis of the
disease. However CaP treatments mostly target AR signaling which is initially
effective but eventually leads to androgen resistance, hence simultaneous
targeting of ERs has been proposed. A novel series of molecules were designed
with multiple sex-steroid receptor modulating capabilities by coalescing the
pharmacophores of known anti-CaP molecules that act via modulation of
ER(alpha/beta) and/or AR, viz. 3,3'diindolylmethane (DIM), mifepristone,
toremifene, tamoxifen and raloxifene. N,N-diethyl-4-((2-(4-methoxyphenyl)-1H
indol-3-yl)methyl) aniline (DIMA) was identified as the most promising structure
of this new series. DIMA increased annexin-V labelling, cell-cycle arrest and
caspase-3 activity, and decreased expression of AR and prostate specific antigen
in LNCaP cells, in vitro. Concurrently, DIMA increased ER-beta, p21 and p27
protein levels in LNCaP cells and exhibited ~5 times more selective binding for
ER-beta than ER-alpha, in comparison to raloxifene. DIMA exhibited a dose
dependent ER-beta agonism and ER-alpha antagonism in classical gene reporter
assay and decreased hTERT (catalytic subunit of telomerase) transcript levels in
LNCaP at 3.0 MUM (P<0.05). DIMA also dose-dependently decreased telomerase enzyme
activity in prostate cancer cells. It is thus concluded that DIMA acts as a multi
steroid receptor modulator and effectively inhibits proliferation of prostate
cancer cells through ER-beta mediated telomerase inhibition, by countering
actions of ER-alpha and AR. Its unique molecular design can serve as a lead
structure for generation of potent agents against endocrine malignancies like the
CaP.
PMID- 25123792
TI - Acute kidney injury in critical care: experience of a conservative strategy.
AB - PURPOSE: Renal replacement therapy (RRT) is a major supportive treatment of acute
kidney injury (AKI) in intensive care unit (ICU), but the timing of its
initiation remains open to debate. MATERIALS AND METHODS: We retrospectively
analyzed ICU patients who had AKI associated with at least one usual RRT
criteria: serum creatinine concentration greater than 300 MUmol/L, serum urea
concentration greater than 25 mmol/L, serum potassium concentration greater than
6.5 mmol/L, severe metabolic acidosis (arterial blood pH<7.2), oliguria (urine
output<135 mL/8 hours or <400 mL/24 hours), overload pulmonary edema. To estimate
the risk of death associated with RRT adjusted for risk factors, we performed a
marginal structural Cox model with inverse-probability-of-treatment-weighted
estimator. RESULTS: Among 4173 patients admitted to the ICU, 203 patients
fulfilled potential RRT criteria. Ninety-one patients (44.8%) received RRT and
112 (55.2%) did not. Non-RRT and RRT patients differed in terms of severity of
illness: Simplified Acute Physiology Score II (55+/-17 vs 60+/-19, respectively;
P<.05) and Sequential Organ Failure Assessment score (8 [5-10] vs 9 [7-11],
respectively; P=.01). Crude analysis indicated a lower ICU mortality for non-RRT
compared with RRT patients (18% vs 45%; P<.001). In the marginal structural Cox
model, RRT was associated with increased mortality (P<.01). CONCLUSION: A
conservative approach of AKI was not associated with increased mortality.
PMID- 25123793
TI - Neurocritical care complications of pregnancy and puerperum.
AB - Neurocritical care complications of pregnancy and puerperum such as
preeclampsia/eclampsia, hemolysis, elevated liver enzymes, low platelets
syndrome, thrombotic thrombocytopenic purpura, seizures, ischemic and hemorrhagic
stroke, postpartum angiopathy, cerebral sinus thrombosis, amniotic fluid emboli,
choriocarcinoma, and acute fatty liver of pregnancy are rare but can be
devastating. These conditions can present a challenge to physicians because
pregnancy is a unique physiologic state, most therapeutic options available in
the intensive care unit were not studied in pregnant patients, and in many
situations, physicians need to deliver care to both the mother and the fetus,
simultaneously. Timely recognition and management of critical neurologic
complications of pregnancy/puerperum can be life saving for both the mother and
fetus.
PMID- 25123794
TI - Intensivist perceptions of family-centered rounds and its impact on physician
comfort, staff involvement, teaching, and efficiency.
AB - PURPOSE: Our goal was to examine intensivists' perception of comfort, staff
satisfaction, teaching, and efficiency with family-centered rounds (FCR).
MATERIALS AND METHODS: Surveys were sent to intensivists at Emory University.
Responses of physicians that participate in FCR were compared with those who do
not. Survey questions were developed using a 5-point Likert scale with 1
representing a negative response and 5 being positive. RESULTS: Of 46 surveys
sent, there were 31 responses (response rate, 67%). Seventeen responses were from
adult intensivists and 14 from pediatric. Sixteen respondees (52%) participate in
FCR, whereas 15 respondents (48%) do not. There is a significant difference in
physician comfort with the practice with an average score of 4.4+1.0 for those
who participate and 2.7+1.7 for those who do not (P=.002). There is also a
significant difference in the perception of the impact of FCR on staff. Those who
participate feel that it has a significantly greater positive impact on staff's
involvement during rounds with an average score of 3.6+1.2 vs an average score of
2.3+1.2 for those who do not practice FCR (P=.003). Those who participate in FCR
have significantly more positive perception on its impact on patient outcomes
with an average score of 3.8+1.1 compared with an average score of 2.9+1.3 for
those who do not participate in FCR (P=.05). There are no significant differences
in perceptions on teaching and efficiency among participants and nonparticipants
in FCR. CONCLUSIONS: Participation in FCR is associated with an increase in
perceived physician comfort, positive impact on staff involvement, and positive
impact on patient outcome. Concerns over teaching and efficiency remain.
PMID- 25123798
TI - The relationship between revascularization extent and the long-term prognosis of
patients with stable angina pectoris and three-vessel disease treated by
percutaneous coronary intervention in the era of drug-eluting stents.
AB - BACKGROUND: The effects of revascularization extent (RE) on the long-term
prognosis of patients with stable angina pectoris and 3-vessel disease who
underwent percutaneous coronary intervention were unknown. HYPOTHESIS: The study
was aimed at evaluating whether there was an effect of RE on patients presenting
with stable angina pectoris and 3-vessel disease. METHODS: RE, which was
calculated by baseline SYNTAX (Synergy Between Percutaneous Coronary Intervention
With Taxus and Cardiac Surgery) score minus residue SYNTAX score divided by
baseline SYNTAX score, was initially used in our study. Five hundred fifty-eight
patients presenting with stable angina pectoris and 3-vessel disease were
assigned to and compared among tertiles according to RE and clinical outcomes.
The primary end point was the major adverse cardiovascular event (MACE), a
composite of cardiac death, nonfatal myocardial infarction (MI), and any repeat
revascularization. RESULTS: The median follow-up period was 56.9 months
(interquartile range, 52.1-63.6). The incidence of MACE increased significantly
as RE increased (13.3%, 31.4%, and 44.1%, log-rank P < 0.001). The same tendency
was observed in occurrences of target-vessel failure (TVF) (a composite of
cardiac death, MI, or target-vessel revascularization) (8.8%, 20.3%, and 28.4%,
log-rank P < 0.001), repeat revascularization (11.8%, 26.2%, and 35.6%, log-rank
P < 0.001), and MI (1.1%, 2.9%, and 12.6%, log-rank P < 0.001). Multivariate
analysis confirmed the tendencies mentioned above. CONCLUSIONS: For patients
presenting with stable angina pectoris and 3-vessel disease, the increasing
extent of revascularization resulted in a less favorable prognosis.
PMID- 25123799
TI - [Laparoscopic liver surgery].
AB - Liver resection remains the method of choice for curative treatment for liver
tumors. Development in diagnostic and surgical techniques has improved operative
results as well as long-term outcomes. In the last decade minimally invasive
laparoscopic (LAP) surgery has been increasingly adopted by liver units. The
trend in LAP liver resection has been moving from limited resections towards
major hepatectomy. This process, however, is relatively slow, which can be due to
technical difficulties of the procedure and fear of haemorrhage. Despite having a
hard time at the start, major resections become more common. Up to now
approximately 6000 LAP liver resections were performed worldwide, number of major
hepatectomies is estimated between 700-800. LAP liver resections are feasible
with significant benefits for patients consisting of less blood loss, less
narcotic requirements, and shorter hospital stay with comparable postoperative
morbidity and mortality to open liver resections. It is an accepted management of
both benign and malignant liver lesions. There is no difference between LAP and
open surgery in late survival after resection for colorectal liver metastases.
Overall survival of LAP resected hepatocellular carcinoma cases seems to be
superior compared with open surgery.
PMID- 25123797
TI - Differential infection outcome of Chlamydia trachomatis in human blood monocytes
and monocyte-derived dendritic cells.
AB - BACKGROUND: Chlamydia trachomatis is an intracellular bacteria which consist of
three biovariants; trachoma (serovars A-C), urogenital (serovars D-K) and
lymphogranuloma venereum (L1-L3), causing a wide spectrum of disease in humans.
Monocytes are considered to disseminate this pathogen throughout the body while
dendritic cells (DCs) play an important role in mediating immune response against
bacterial infection. To determine the fate of C. trachomatis within human
peripheral blood monocytes and monocyte-derived DCs, these two sets of immune
cells were infected with serovars Ba, D and L2, representative of the three
biovariants of C. trachomatis. RESULTS: Our study revealed that the different
serovars primarily infect monocytes and DCs in a comparable fashion, however
undergo differential infection outcome, serovar L2 being the only candidate to
inflict active infection. Moreover, the C. trachomatis serovars Ba and D become
persistent in monocytes while the serovars predominantly suffer degradation
within DCs. Effects of persistence gene Indoleamine 2, 3-dioxygenase (IDO) was
not clearly evident in the differential infection outcome. The heightened levels
of inflammatory cytokines secreted by the chlamydial infection in DCs compared to
monocytes seemed to be instrumental for this consequence. The immune genes
induced in monocytes and DCs against chlamydial infection involves a different
set of Toll-like receptors, indicating that distinct intracellular signalling
pathways are adopted for immune response. CONCLUSION: Our results demonstrate
that the host pathogen interaction in chlamydia infection is not only serovar
specific but manifests cell specific features, inducing separate immune response
cascade in monocytes and DCs.
PMID- 25123800
TI - [Is daily chest X-ray necessary after lung resection? Evidence-based decision
making].
AB - OBJECTIVES: The 'gold standard' practice following insertion of a chest tube
after lobectomy is daily chest radiography (CXR), but this is not always
followed. We compared the outcomes associated with the use of these two methods
in our practice. METHODS: Data from 148 patients who underwent uncomplicated
lobectomies with insertion of one chest drain were analysed. In the routine CXR
group (R-CXR) (50 patients), an immediate postoperative CXR, daily routine
radiography during the drainage period, and one after surgical drain removal were
performed. In the symptomatic CXR group (S-CXR) (98 patients), a CXR was
performed only for symptomatic patients (fever, hypoxia, subcutaneous emphysema,
air leak) and/or a single radiograph was taken after surgical drain removal. The
following postoperative data were compared: fever, CXR abnormalities
(pneumothorax, fluid, atelectasis, subcutaneous emphysema, haematoma), number of
radiographs, drainage time, and new drain insertion. RESULTS: The mean chest tube
duration was 3.7 and 3.8 days in the R-CXR and S-CXR groups, respectively.
Abnormal CXRs after surgical drain removal were reported in 50% (25/50) and 46.9%
(46/96) (p = 0.724) of patients in the R-CXR and S-CXR groups, respectively, but
new drain insertion was only necessary in 3/25 (12%) and 7/46 (15.2%) of these
cases. The mean number of CXRs for each patient was 5.0 and 2.3 (p = 0.0001) in
the R-CXR and S-CXR groups, respectively. CONCLUSIONS: If CXRs are limited to
symptomatic patients then the number of radiographs can be reduced by around 50%.
There were no more postoperative complications or abnormal final CXR findings if
the CXR was only ordered for symptomatic patients instead of as 'daily routine'
during the postoperative period. Only 12-15% of the CXR abnormalities required
surgical intervention.
PMID- 25123801
TI - [Outcomes following rectal and recto-sigmoid cancer resections: comparison of the
laparoscopic and open techniques].
AB - BACKGROUND/AIMS: Surgical technique and experience are considered as significant
determinants of the successful treatment of recto-sigmoid malignancies. METHODS:
Two hundred patients operated on between 2005 and 2009 were prospectively
followed with an average of 39.8 months. Patients with rectosigmoid or rectal
cancer were included, either with primary resection or resection after
neoadjuvant therapy. The primary aim was to assess the average survival in the
two groups; secondary outcomes were stage specific survival and the incidence of
loco-regional recurrence and distant metastases. Intra- and postoperative
complications, operating time, onco-pathological specimen quality and length of
stay were also analysed. RESULTS: During the follow-up comparable rates for 3
year survival and recurrence rates were found without statistical difference.
Hospital stay in the laparoscopic group was significantly shorter and the mid
term survival rates were also better in the more advanced stages. Incisional
hernia rate was significantly lower in the laparoscopic group. CONCLUSIONS: The
results of laparoscopic rectal and recto-sigmoid resections were not inferior,
and - in some aspects - they were even better compared to open procedures. Adding
the properties of the minimally invasive technique (shorter recovery, reduced
surgical stress reaction) this should be the preferred method of operative
approach.
PMID- 25123802
TI - [Massive localized lymphoedema (MLL) in the mons pubis].
AB - Massive localized lymphoedema (MLL) is a relatively frequent complication in
obesity. MLL is present as a giant swelling and associated with characteristic
skin changes. Due to the pathologic and morphologic similarity to sarcoma, MLL is
also called "pseudosarcoma". MLL can degenerate into angiosarcoma without
surgery. We present a case of MLL of the mons pubis in a 54-year-old man with a
BMI of 48.6.
PMID- 25123803
TI - [Treatment of pregnancy-associated breast cancer].
AB - CASE REPORT: A 25-year-old primipara, in the thirty-second week of her pregnancy
observed a nodule in the upper outer quadrant of her left breast during self
examination. Complex breast examination revealed calcification with 4 cm of
diameter. Ductal malignant cells (C5) were identified by fine-needle aspiration
biopsy, while core biopsy verified invasive ductal carcinoma, grade III (B5b). No
manifestations of metastases were presented. After pregnancy termination wide
excision with additional axillary sentinel lymph node biopsy was performed.
Because of its positivity block dissection of axillary lymph nodes was carried
out. The surgical therapy was followed by adjuvant chemo-, radio- and hormonal
therapy. Later an angiomyxoma appeared in the right inguinal region, which was
excised in toto. DISCUSSION: The incidence of pregnancy related malignant
diseases is increasing, of which breast cancer predominates. Breast cancer, which
is diagnosed during pregnancy or within the first year of delivery is called
pregnancy-associated breast cancer. Because of the physiological changes in
pregnancy the recognition of the disease is difficult. Therapy is complex, as
besides the treatment of the mother, the safety of the fetus should be
emphasized. The treatment strategies are different in the three trimesters. The
surgical treatment can be performed during the whole pregnancy. The use of
radiotherapy is controversial, because of teratogenic effects, while chemotherapy
is permitted in the second and third trimesters. Nearly three years after the
operation, our patient does not have any symptoms, her son is healthy.
PMID- 25123807
TI - Introduction: celebrating the international year of crystallography:
introduction.
PMID- 25123806
TI - Induced sputum eicosanoids during aspirin bronchial challenge of asthmatic
patients with aspirin hypersensitivity.
AB - BACKGROUND: Altered metabolism of eicosanoids is a characteristic finding in
aspirin-exacerbated respiratory disease (AERD). Bronchial challenge with lysyl
aspirin can be used as a confirmatory diagnostic test for this clinical
condition. Induced sputum allows to measure mediators of asthmatic inflammation
in bronchial secretions. OBJECTIVES: To investigate the influence of inhaled
lysyl-aspirin on sputum supernatant concentration of eicosanoids during the
bronchial challenge test. Subjects with asthma hypersensitive to nonsteroidal
anti-inflammatory drugs were compared with aspirin-tolerant asthmatic controls.
METHODS: Induced sputum was collected before and following bronchial challenge
with lysyl-aspirin. Sputum differential cell count and sputum supernatant
concentrations of selected lipoxygenases products: 5-,12-,15
hydroxyeicosatetraenoic acid, cysteinyl leukotrienes, leukotriene B4 , 11-dehydro
thromboxane B2 , and prostaglandins E2 , D2 , and F2alpha and their metabolites,
were measured using validated methods of chromatography-mass spectrometry.
RESULTS: Aspirin precipitated bronchoconstriction in all AERD subjects, but in
none of the aspirin-tolerant asthmatics. Phenotypes of asthma based on the sputum
cytology did not differ between the groups. Baseline sputum eosinophilia
correlated with a higher leukotriene D4 (LTD4 ) and leukotriene E4 (LTE4 )
concentrations. LTC4 , PGE2 , and 11-dehydro-TXB2 did not differ between the
groups, but levels of LTD4 , LTE4 , and PGD2 were significantly higher in AERD
group. Following the challenge, LTD4 and LTE4 increased, while PGE2 and LTB4
decreased in AERD subjects only. CONCLUSIONS: During the bronchial challenge,
decrease in PGE2 and its metabolite is accompanied by a surge in
bronchoconstrictory cysteinyl leukotrienes produced at the expense of LTB4 in
AERD subjects. Bronchial PGE2 inhibition in AERD seems specific and sensitive to
a low dose of aspirin.
PMID- 25123808
TI - Characterisation of a collection of Streptococcus pneumoniae isolates from
patients suffering from acute exacerbations of chronic bronchitis: in vitro
susceptibility to antibiotics and biofilm formation in relation to antibiotic
efflux and serotypes/serogroups.
AB - The correlation between Streptococcus pneumoniae serotypes, biofilm production,
antibiotic susceptibility and drug efflux in isolates from patients suffering
from acute exacerbations of chronic bronchitis (AECB) remains largely unexplored.
Using 101 isolates collected from AECB patients for whom partial (n=51) or full
(n=50) medical details were available, we determined serotypes (ST)/serogroups
(SG) (Quellung reaction), antibiotic susceptibility patterns [MIC (microdilution)
using EUCAST and CLSI criteria] and ability to produce biofilm in vitro (10-day
model; crystal violet staining). The majority of patients were 55-75 years old
and <5% were vaccinated against S. pneumoniae. Moreover, 54% showed high severity
scores (GOLD 3-4), and comorbidities were frequent including hypertension (60%),
cancer (24%) and diabetes (20%). Alcohol and/or tobacco dependence was >30%.
Isolates of SG6-11-15-23, known for large biofilm production and causing chronic
infections, were the most prevalent (>15% each), but other isolates also produced
biofilm (SG9-18-22-27 and ST8-20 being most productive), except SG7, SG29 and ST5
(<2% of isolates each). Resistance (EUCAST breakpoints) was 8-13% for amoxicillin
and cefuroxime, 35-39% for macrolides, 2-8% for fluoroquinolones and 2% for
telithromycin. ST19A isolates showed resistance to all antibiotics, ST14 to all
except moxifloxacin, and SG9 and SG19 to all except telithromycin, moxifloxacin
and ceftriaxone (SG19 only). Solithromycin and telithromycin MICs were similar.
No correlation was observed between biofilm production and MIC or efflux
(macrolides, fluoroquinolones). S. pneumoniae serotyping may improve AECB
treatment by avoiding antibiotics with predictable low activity, but it is not
predictive of biofilm production.
PMID- 25123809
TI - Emergence of Klebsiella pneumoniae co-producing NDM-1, OXA-48, CTX-M-15, CMY-16,
QnrA and ArmA in Switzerland.
AB - Extensively drug-resistant (XDR) Klebsiella pneumoniae isolates usually carry a
single carbapenemase (e.g. KPC, NDM, OXA-48-like). Here we describe an XDR K.
pneumoniae of sequence type 101 that was detected in the screening rectal swab of
a patient transferred from the intensive care unit of a hospital located in
Belgrade (Serbia) to Bern University Hospital (Switzerland). The isolate was
resistant to all antibiotics with the exception of colistin [minimum inhibitory
concentration] (MIC <= 0.125 MUg/mL), tigecycline (MIC = 0.5 MUg/mL) and
fosfomycin (MIC = 2 MUg/mL). The isolate co-possessed class B (NDM-1) and class D
(OXA-48) carbapenemases, class A extended-spectrum beta-lactamase (CTX-M-15),
class C cephalosporinase (CMY-16), ArmA 16S rRNA methyltransferase, substitutions
in GyrA and ParC, loss of OmpK35 porin, as well as other genes conferring
resistance to quinolones (qnrA), tetracyclines [tet(A)], sulfonamides (sul1,
sul2), trimethoprim (dfrA12, dfrA14), rifampicin (arr-1), chloramphenicol (cmlA1,
floR) and streptomycin (aadA1). The patient was placed under contact isolation
precautions preventing the spread of this nearly untreatable pathogen.
PMID- 25123810
TI - Reversal of meticillin resistance in Staphylococcus aureus by the anthelmintic
avermectin.
PMID- 25123811
TI - Antifungal prophylaxis in lung transplantation.
AB - Lung transplant (LTx) patients have an increased risk of developing invasive
fungal infections (IFIs), particularly invasive aspergillosis. Rapid
identification of the causative fungal pathogen, to allow for early
administration of appropriate initial antifungal therapy, in LTx patients has
been challenging due to the limited sensitivity and specificity of the diagnostic
tools. Hence, there is increasing emphasis on antifungal prophylaxis in the LTx
setting, given the high mortality rates and substantial cost of treating IFIs.
Evidence for the optimal antifungal prophylactic approach in this setting,
however, remains scant and inconsistent. This review will briefly discuss the
epidemiology, risk factors, timing and clinical manifestations of fungal
infections in LTx patients and will focus primarily on the available evidence
related to the efficacy, safety and practicality of current prophylactic
strategies in LTx recipients as well as challenges and gaps for future research.
PMID- 25123812
TI - The relationships among dyspnoea, health-related quality of life and
psychological factors in sarcoidosis.
AB - BACKGROUND AND OBJECTIVES: Dyspnoea is a common symptom in sarcoidosis and is not
predictably related to pulmonary function or radiology. A subjective symptom of
dyspnoea is likely to be influenced by patient perception and experience. The aim
of this study was to determine the prevalence and nature of dyspnoea in
sarcoidosis and describe the relationship of dyspnoea to psychological factors
and health-related quality of life (HRQL). METHODS: Fifty-six subjects (31 men,
mean age 51 years) with sarcoidosis completed an HRQL measure, St George's
Respiratory Questionnaire (SGRQ), Hospital Anxiety and Depression Scale (HADS)
and Nijmegen questionnaire. The presence of symptoms of dyspnoea was noted and
qualitative descriptors for dyspnoea were chosen at peak exercise. Resting
pulmonary function was performed. RESULTS: Sixty-four per cent of the subjects
reported dyspnoea. Those with symptoms were older, had a longer duration of
disease and with lower forced expiratory volume in 1 s (FEV1 ) and FEV1 /forced
vital capacity (FVC) (all P < 0.05). Symptoms of dyspnoea were associated with
worse HRQL (P < 0.005) and higher scores on the Nijmegen questionnaire (P <
0.05). Anxiety was not associated with dyspnoea and only a trend to greater
depression was observed (P = 0.066). In multivariate analysis, SGRQ and Nijmegen
scores predicted dyspnoea independent of demographic factors and resting
pulmonary function. CONCLUSION: Dyspnoea is common in sarcoidosis and is
associated with worse HRQL irrespective of baseline pulmonary function.
Hyperventilation appears to be a factor contributing to dyspnoea and the Nijmegen
questionnaire may be helpful in assessing dyspnoea and hyperventilation in
sarcoidosis patients.
PMID- 25123813
TI - Micropapillary urothelial carcinoma in a renal transplant recipient: a case
report on urine cytomorphology emphasizing differentiation from high-grade
urothelial carcinoma.
PMID- 25123815
TI - An holistic approach to beach erosion vulnerability assessment.
AB - Erosion is a major threat for coasts worldwide, beaches in particular, which
constitute one of the most valuable coastal landforms. Vulnerability assessments
related to beach erosion may contribute to planning measures to counteract
erosion by identifying, quantifying and ranking vulnerability. Herein, we present
a new index, the Beach Vulnerability Index (BVI), which combines simplicity in
calculations, easily obtainable data and low processing capacity. This approach
provides results not only for different beaches, but also for different sectors
of the same beach and enables the identification of the relative significance of
the processes involved. It functions through the numerical approximation of
indicators that correspond to the mechanisms related to the processes that
control beach evolution, such as sediment availability, wave climate, beach
morhodynamics and sea level change. The BVI is also intended to be used as a
managerial tool for beach sustainability, including resilience to climate change
impact on beach erosion.
PMID- 25123814
TI - High incidence of spontaneous cataracts in aging laboratory rabbits of an inbred
strain.
AB - OBJECTIVE: To investigate the occurrence of spontaneous cataracts in a breeding
colony of the inbred EIII/JC strain of New Zealand White rabbits (Oryctolagus
cuniculi) and the congenic strain of EIII/JC-HLA-A2.1transgenic rabbits.
PROCEDURE: A retrospective study was conducted by collecting and analyzing data
from clinical records for individual rabbits filed between January 2011 and
October 2013. RESULTS: Thirteen cases (eight females and five males) of cataract
were identified in a group of 51 EIII/JC inbred rabbits with a morbidity of
25.5%. The median age of the rabbits identified with unilateral or bilateral
cataracts was 43 months in contrast to the median age of 23 months of the entire
group of 51 rabbits. Additionally, seven cases (five females and two males) of
cataracts were identified in a group of 21 EIII/JC-HLA-A2.1 transgenic rabbits.
The EIII/JC-HLA-A2.1 transgenic rabbits showed similar morbidity (33.3%) and
median age (41 months) for the development of cataracts as the EIII/JC rabbits.
In both groups, none of the rabbits younger than 37 months developed cataracts
while 13 (93%) of 14 EIII/JC rabbits aged 37-49 months and seven (63.6%) of 11
EIII/JC-HLA-A2.1 transgenic rabbits aged 37-43 months developed cataracts. In
contrast, none of 78 outbred rabbits with a median age of 26 months (10-67
months) developed cataracts. CONCLUSION: Results of this study indicate that the
occurrence and high incidence of spontaneous cataracts in this inbred strain
(EIII/JC) of rabbits were strictly age related and consistently transmitted
through inbreeding.
PMID- 25123816
TI - Lipase-mediated lipid removal from propolis extract and its antiradical and
antimicrobial activity.
AB - BACKGROUND: Propolis contains many antioxidants such as polyphenols and
flavonoids. However, propolis-derived lipid components interrupt an efficient
isolation of antioxidants from propolis extract. We examined the effectiveness of
various lipase treatments for the removal of lipids from propolis extract and
evaluated the biological features of the extract. RESULTS: Lipase OF and Novozyme
435 treatments did not reduce fatty acid level in propolis extract. However,
Lipozyme TL IM-treated propolis extract showed a significant decrease in fatty
acid level, suggesting the removal of lipids. Lipozyme RM IM also significantly
decreased the fatty acid level of the extract, but was accompanied by the
reduction of polyphenols and flavonoids, which are antioxidants. In Lipozyme TL
IM treatment, an increase in active flavonoids, such as Artepillin C and
kaempferide, was observed, with a slight increase of ferric reducing/antioxidant
power (FRAP) radical-scavenging activity. In addition, antimicrobial activity
towards skin health-related bacteria such as Staphylococcus epidermidis and
Propionibacterium acnes was enhanced by Lipozyme TL IM treatment. CONCLUSION:
Lipozyme TL IM treatment effectively removes lipids from propolis extract and
enhances antibacterial activity. Therefore, we suggest that Lipozyme TL IM is a
useful lipase for lipid removal of propolis extract.
PMID- 25123817
TI - Continuation and effectiveness of tadalafil once daily during a 6-month
observational study in erectile dysfunction: the EDATE study.
AB - AIMS: This was the first observational study evaluating treatment continuation,
effectiveness and tolerability of tadalafil 5 mg once daily (TAD-OaD) in patients
who chose and paid for treatment of erectile dysfunction (ED) in routine clinical
practice. METHODS: Men >= 18 years with ED, treated previously with
phosphodiesterase type 5 (PDE5)-inhibitor on-demand (PRN) or treatment-naive,
were enrolled at 59 sites. For patients prescribed TAD-OaD at baseline (T1),
change in erectile function (IIEF-EF and GAQ) was documented after 1-3 (T2) and 4
6 (T3) months. The primary outcome was the probability to switch/discontinue from
TAD-OaD, estimated by Kaplan-Meier (KM) product-limit method. Changes in IIEF-EF
were evaluated using a mixed model for repeated measures adjusting for patient
baseline characteristics. RESULTS: Of 975 men enrolled (median age 56.8 years,
33.7% with previous PDE5-inhibitor use), 778 were prescribed TAD-OaD, 135 TAD-PRN
and 62 sildenafil or vardenafil PRN. During the 6-month longitudinal observation,
107 patients (13.8% of 778) switched or discontinued TAD-OaD-treatment. KM-rates
(95%CI) for continuing TAD-OaD at 2, 4 and 6 months were 94.0% (92.3, 95.7),
88.3% (85.9, 90.6) and 86.3% (83.7, 88.9), respectively. The 25th percentile of
time to switch/discontinuation of TAD-OaD was estimated as 31.1 weeks (lower
95%CI 30.3 weeks). At T3, IIEF-EF scores had increased by 7.1 (LSmean; 95%CI 5.8,
8.5) points; 91.3% of patients reported improved erections. The most frequently
reported AE was headache (10 patients; 1.3%); no new/unexpected safety signals
were observed. CONCLUSION: Under routine conditions, and when patients were
involved in treatment decision-making, more than 86% of men starting/switching to
tadalafil once daily (OaD) at baseline continued tadalafil OaD treatment for >= 6
months.
PMID- 25123818
TI - TRAIL expression levels in human hepatocellular carcinoma have implications for
tumor growth, recurrence and survival.
AB - The proapoptotic molecule TNF-related apoptosis-inducing ligand (TRAIL) has
earned attention because of its ability to induce apoptosis in liver cancer cells
without damaging normal liver cells. It may play an important role in preventing
the development and outgrowth of hepatocellular carcinoma (HCC). TRAIL expression
was investigated in a large series of human HCCs. We analyzed liver tissue from
108 patients undergoing partial liver resection (PLR) or liver transplantation
(LT) because of either HCC or other indications. TRAIL expression was correlated
with the cause of liver disease, demographic and clinical variables and
pathologic properties. Our analysis found that in 66% of HCCs TRAIL expression
was significantly lower than in the surrounding non-cancerous liver tissue
(p<=0.012). Separation by cause of disease showed that HCC TRAIL mRNA expression
was lower in almost all groups than in non-cancerous tissue but most
significantly lower in NASH-associated liver tumors. Interestingly, low HCC TRAIL
expression was found to correlate with tumor size (p<=0.007) and stage, as well
as with tumor recurrence after resection and poor survival rates. The results of
this study suggest that low TRAIL mRNA levels may be both a dominant feature in
HCC development and growth and a predictor of tumor recurrence and poorer
survival rates.
PMID- 25123820
TI - Comparison of in vivo and in vitro properties of capsulated and noncapsulated
variants of Mycoplasma mycoides subsp. mycoides strain Afade: a potential new
insight into the biology of contagious bovine pleuropneumonia.
AB - Mycoplasma mycoides subsp. mycoides (Mmm) strain Afade had previously been shown
to undergo spontaneous phase variations between an opaque capsulated variant and
a translucent (TR) variant devoid of a capsule but able to secrete cell-free
exopolysaccharides. This phase variation is associated with an ON/OFF genetic
switch in a glucose permease gene. In this study, in vivo and in vitro assays
were conducted to compare the virulence of the two variants and their abilities
to resist host defence. Capsulated variants were shown, in a mouse model, to
induce longer bacteraemia that was correlated with better serum resistance in
vitro. In contrast, TR variants displayed better ability to adhere to an inert
support, linked to the absence of a capsule, changes in cell surface
hydrophobicity and increased resistance to antimicrobial peptide and hydrogen
peroxide. The switch from one variant population to another, which was observed
both in vivo and in vitro under stress conditions, is further discussed as a
means for Mmm to modulate its interactions with animal hosts during different
stages of the disease.
PMID- 25123821
TI - N8 (-) polynitrogen stabilized on multi-wall carbon nanotubes for oxygen
reduction reactions at ambient conditions.
AB - Polynitrogen (PN) species (Nn , n from 3 to 8) as highly energetic materials have
attracted many theoretical calculations and predictions. N3 , N4 , N5 or their
ions were experimentally detected under high-pressure and high-temperature
conditions. Herein, a N8 (-) PN stabilized on the positively charged sidewalls of
multi-walled carbon nanotubes (MWNTs) has been synthesized using cyclic
voltammetry (CV) under ambient conditions. ATR-FTIR and Raman spectroscopic data
assigned on the basis of density functional theory (DFT) calculations support the
successful synthesis of a C2h symmetry chain structure of the N8 anion stabilized
as MWNT(+) N8 (-) . Temperature programmed desorption (TPD) data show that
MWNT(+) N8 (-) is thermally stable up to 400 degrees C. Oxygen-reduction
reaction (ORR) experiments carried out using MWNT(+) N8 (-) as the cathodic
catalyst shows that it is very active for ORR with an even higher current density
than that of a commercial Pt/carbon catalyst.
PMID- 25123822
TI - A randomized comparative trial of two decision tools for pregnant women with
prior cesareans.
AB - OBJECTIVE: Evaluate tools to help pregnant women with prior cesareans make
informed decisions about having trials of labor. DESIGN: Randomized comparative
trial. SETTING: A research assistant with a laptop met the women in quiet
locations at clinics and at health fairs. PARTICIPANTS: Pregnant women (N = 131)
who had one prior cesarean and were eligible for vaginal birth after cesarean
(VBAC) participated one time between 2005 and 2007. METHODS: Women were
randomized to receive either an evidence-based, interactive decision aid or two
evidence-based educational brochures about cesarean delivery and VBAC. Effect on
the decision-making process was assessed before and after the interventions.
RESULTS: Compared to baseline, women in both groups felt more informed (F = 23.8,
p < .001), were more clear about their birth priorities (F = 9.7, p = .002), felt
more supported (F = 9.8, p = .002, and overall reported less conflict (F = 18.1,
p < 0.001) after receiving either intervention. Women in their third trimesters
reported greater clarity around birth priorities after using the interactive
decision aid than women given brochures (F = 9.8, p = .003). CONCLUSION: Although
both decision tools significantly reduced conflict around the birth decision
compared to baseline, more work is needed to understand which format, the
interactive decision aid or paper brochures, are more effective early and late in
pregnancy.
PMID- 25123819
TI - Can we unlock the potential of IGF-1R inhibition in cancer therapy?
AB - IGF-1R inhibitors arrived in the clinic accompanied by optimism based on
preclinical activity of IGF-1R targeting, and recognition that low IGF
bioactivity protects from cancer. This was tempered by concerns about toxicity to
normal tissue IGF-1R and cross-reactivity with insulin receptor (InsR). In fact,
toxicity is not a show-stopper; the key issue is efficacy. While IGF-1R
inhibition induces responses as monotherapy in sarcomas and with chemotherapy or
targeted agents in common cancers, negative Phase 2/3 trials in unselected
patients prompted the cessation of several Pharma programs. Here, we review
completed and on-going trials of IGF-1R antibodies, kinase inhibitors and ligand
antibodies. We assess candidate biomarkers for patient selection, highlighting
the potential predictive value of circulating IGFs/IGFBPs, the need for
standardized assays for IGF-1R, and preclinical evidence that variant InsRs
mediate resistance to IGF-1R antibodies. We review hypothesis-led and unbiased
approaches to evaluate IGF-1R inhibitors with other agents, and stress the need
to consider sequencing with chemotherapy. The last few years were a tough time
for IGF-1R therapeutics, but also brought progress in understanding IGF biology.
Even failed studies include patients who derived benefit; they should be
investigated to identify features distinguishing the tumors and host environment
of responders from non-responders. We emphasize the importance of incorporating
biospecimen collection into trial design, and wording patient consents to allow
post hoc analysis of trial material as new data become available. Such
information represents the key to unlocking the potential of this approach, to
inform the next generation of trials of IGF signalling inhibitors.
PMID- 25123823
TI - Costs of care for persons with opioid dependence in commercial integrated health
systems.
AB - BACKGROUND: When used in general medical practices, buprenorphine is an effective
treatment for opioid dependence, yet little is known about how use of
buprenorphine affects the utilization and cost of health care in commercial
health systems. METHODS: The objective of this retrospective cohort study was to
examine how buprenorphine affects patterns of medical care, addiction medicine
services, and costs from the health system perspective. Individuals with two or
more opioid-dependence diagnoses per year, in two large health systems (System A:
n = 1836; System B: n = 4204) over the time span 2007-2008 were included.
Propensity scores were used to help adjust for group differences. RESULTS:
Patients receiving buprenorphine plus addiction counseling had significantly
lower total health care costs than patients with little or no addiction treatment
(mean health care costs with buprenorphine treatment = $13,578; vs. mean health
care costs with no addiction treatment = $31,055; p < .0001), while those
receiving buprenorphine plus addiction counseling and those with addiction
counseling only did not differ significantly in total health care costs (mean
costs with counseling only: $17,017; p = .5897). In comparison to patients
receiving buprenorphine plus counseling, those with little or no addiction
treatment had significantly greater use of primary care (p < .001), other medical
visits (p = .001), and emergency services (p = .020). Patients with counseling
only (compared to patients with buprenorphine plus counseling) used less
inpatient detoxification (p < .001), and had significantly more PC visits (p =
.001), other medical visits (p = .005), and mental health visits (p = .002).
CONCLUSIONS: Buprenorphine is a viable alternative to other treatment approaches
for opioid dependence in commercial integrated health systems, with total costs
of health care similar to abstinence-based counseling. Patients with
buprenorphine plus counseling had reduced use of general medical services
compared to the alternatives.
PMID- 25123825
TI - Haemolytic anaemia associated with Theileria sp. in an orphaned platypus.
AB - CASE REPORT: The clinical and laboratory findings in an orphaned juvenile female
platypus (Ornithorhynchus anatinus) that presented with a severe anaemia and tick
infestation are reported. The animal developed a terminal septicaemia and died.
Antemortem clinical pathology, postmortem histopathology and 18S rDNA sequencing
supported a diagnosis of extravascular haemolytic anaemia secondary to Theileria
ornithorhynchi infection. CONCLUSION: Although T. ornithorhynchi infection is
common in the platypus, this is the first case in which it has been shown to
cause a haemolytic anaemia in this species and molecular characterisation of the
organism has been described. A review of the previous literature concerning T.
ornithorhynchi and possible treatment options for future cases are discussed.
PMID- 25123824
TI - TLR4-dependent activation of dendritic cells by an HMGB1-derived peptide
adjuvant.
AB - High mobility group box protein 1 (HMGB1) acts as an endogenous danger molecule
that is released from necrotic cells and activated macrophages. We have
previously shown that peptide Hp91, whose sequence corresponds to an area within
the B-Box domain of HMGB1, activates dendritic cells (DCs) and acts as an
adjuvant in vivo. Here we investigated the underlying mechanisms of Hp91-mediated
DC activation. Hp91-induced secretion of IL-6 was dependent on clathrin- and
dynamin-driven endocytosis of Hp91 and mediated through a MyD88- and TLR4
dependent pathway involving p38 MAPK and NFkappaB. Endosomal TLR4 has been shown
to activate the MyD88-independent interferon pathway. Hp91-induced activation of
pIRF3 and IL-6 secretion was reduced in IFNalphabetaR knockout DCs, suggesting an
amplification loop via the IFNalphabetaR. These findings elucidate the mechanisms
by which Hp91 acts as immunostimulatory peptide and may serve as a guide for the
future development of synthetic Th1-type peptide adjuvants for vaccines.
PMID- 25123826
TI - Performance of central venous catheterization by medical students: a
retrospective study of students' logbooks.
AB - BACKGROUND: Medical students often learn the skills necessary to perform a
central venous catheterization in the operating room after simulator training. We
examined the performance of central venous catheterization by medical students
from the logbooks during their rotation in department of anesthesiology. METHODS:
From the logbooks of medical students rotating in our department between January
2011 and June 2012, we obtained the kind and the number of central venous
catheterization students had done, the results of the procedures whether they
were success or failed, the reasons of the failures, complications, and the
student self-reported confidence and satisfaction of their performance. RESULTS:
There were 93 medical students performed 875 central venous catheterizations with
landmark guidance on patients in the operating theater, and the mean number of
catheterizations performed per student was 9.4 +/- 2.0, with a success rate of
67.3%. Adjusted for age, sex, body mass index, surgical category, ASA score and
insertion site, the odds of successful catherization improved with cumulative
practice (odds ratio 1.10 per additional central venous catheterization
performed; 95% confidence interval 1.05-1.15). The major challenge students
encountered during the procedure was the difficulty of finding the central veins,
which led to 185 catheterizations failed. The complication rate of central venous
catheterization by the students was 7.8%, while the most common complication was
puncture of artery. The satisfaction and confidence of students regarding their
performance increased with each additional procedure and decreased significantly
if failure or complications had occurred. CONCLUSION: A student logbook is a
useful tool for recording the actual procedural performance of students. From the
logbooks, we could see the students' performance, challenges, satisfaction and
confidence of central venous catheterization were improved through cumulative
clinical practice of the procedure.
PMID- 25123829
TI - Isolated hepatic tuberculosis mimicking liver tumors in a dialysis patient.
AB - Cases of isolated hepatic tuberculosis (TB) are rare. The diagnosis is often
delayed or missed because of nonspecific symptoms and laboratory findings.
Besides, the disease is extremely rare even in a country where TB is an alarming
public health problem. This report demonstrates the difficulty in correctly
diagnosing local hepatic TB. We report the case of a 62-year-old male patient
with end-stage renal disease treated with hemodialysis, who developed 2 months of
abdominal distension and general anorexia, with hyperechoic hepatic lesions on
ultrasound. Computed tomography suspected multiple liver tumors. The liver biopsy
finally led to the diagnosis of TB of the liver without other involvements. We
conclude that isolated hepatic TB is one of the rare forms of extrapulmonary TB
in dialysis patients. A greater awareness of this rare clinical entity may
prevent needless surgical interventions.
PMID- 25123827
TI - Surface tailoring of nanoparticles via mixed-charge monolayers and their
biomedical applications.
AB - The recent convergence of nanomaterials and medicine has provided an expanding
horizon for people to achieve encouraging advances in many biomedical
applications such as cancer diagnosis and therapy. However, to realize desirable
functions in the rather complex biological systems, a suitable surface coating is
greatly in need for nanoparticles (NPs), regardless of the species. In this
review, a recently developed surface modification strategy is highlighted--mixed
charge monolayers--with an emphasis on the nanointerfaces of inorganic NPs. Two
typical mixed-charge gold NPs (AuNPs) prepared from surface modifications with
different combinations of oppositely charged alkanethiols are shown as detailed
examples to discuss how the mixed-charge monolayer can help NPs meet the criteria
for in vitro and in vivo biomedical applications, including those critical issues
like colloidal stability, nonfouling properties, and smart responses (pH
sensitivity) for tumor targeting.
PMID- 25123828
TI - [Scaphoid surgery].
AB - Fracture of the scaphoid is the second most common fracture of the wrist. It
requires a precise diagnosis and an individual therapy tailored to the patient.
Computed tomography has assumed the central role in diagnostics and is obligatory
to perform both verification and planning of treatment. Stable fractures can be
treated conservatively while unstable fractures should be surgically stabilized.
For this procedure different countersink compression screws are available. The
fracture of the proximal pole must be considered separately because it is
associated a very high rate of nonunion. No and incorrect treatment of fresh
scaphoid fractures are the most common reasons for developing scaphoid nonunion.
Depending on the location and perfusion, different surgical procedures including
transplantation of avascular or vascularized bone grafts can be performed for
treatment of scaphoid nonunion.
PMID- 25123830
TI - Analytic power and sample size calculation for the genotypic
transmission/disequilibrium test in case-parent trio studies.
AB - Case-parent trio studies considering genotype data from children affected by a
disease and their parents are frequently used to detect single nucleotide
polymorphisms (SNPs) associated with disease. The most popular statistical tests
for this study design are transmission/disequilibrium tests (TDTs). Several types
of these tests have been developed, for example, procedures based on alleles or
genotypes. Therefore, it is of great interest to examine which of these tests
have the highest statistical power to detect SNPs associated with disease.
Comparisons of the allelic and the genotypic TDT for individual SNPs have so far
been conducted based on simulation studies, since the test statistic of the
genotypic TDT was determined numerically. Recently, however, it has been shown
that this test statistic can be presented in closed form. In this article, we
employ this analytic solution to derive equations for calculating the statistical
power and the required sample size for different types of the genotypic TDT. The
power of this test is then compared with the one of the corresponding score test
assuming the same mode of inheritance as well as the allelic TDT based on a
multiplicative mode of inheritance, which is equivalent to the score test
assuming an additive mode of inheritance. This is, thus, the first time the power
of these tests are compared based on equations, yielding instant results and
omitting the need for time-consuming simulation studies. This comparison reveals
that these tests have almost the same power, with the score test being slightly
more powerful.
PMID- 25123831
TI - Neuroendocrine mechanisms for immune system regulation during stress in fish.
AB - In the last years, the aquaculture crops have experienced an explosive and
intensive growth, because of the high demand for protein. This growth has
increased fish susceptibility to diseases and subsequent death. The constant
biotic and abiotic changes experienced by fish species in culture are challenges
that induce physiological, endocrine and immunological responses. These changes
mitigate stress effects at the cellular level to maintain homeostasis. The
effects of stress on the immune system have been studied for many years. While
acute stress can have beneficial effects, chronic stress inhibits the immune
response in mammals and teleost fish. In response to stress, a signaling cascade
is triggered by the activation of neural circuits in the central nervous system
because the hypothalamus is the central modulator of stress. This leads to the
production of catecholamines, corticosteroid-releasing hormone,
adrenocorticotropic hormone and glucocorticoids, which are the essential
neuroendocrine mediators for this activation. Because stress situations are
energetically demanding, the neuroendocrine signals are involved in metabolic
support and will suppress the "less important" immune function. Understanding the
cellular mechanisms of the neuroendocrine regulation of immunity in fish will
allow the development of new pharmaceutical strategies and therapeutics for the
prevention and treatment of diseases triggered by stress at all stages of fish
cultures for commercial production.
PMID- 25123832
TI - Gender-specific metabolic responses in hepatopancreas of mussel Mytilus
galloprovincialis challenged by Vibrio harveyi.
AB - Mussel Mytilus galloprovincialis is a marine aquaculture shellfish and frequently
studied in shellfish immunology. In this work, the gender-specific metabolic
responses induced by Vibrio harveyi in hepatopancreas from M. galloprovincialis
were characterized using NMR-based metabolomics. In details, V. harveyi challenge
increased the levels of amino acids including (valine, leucine, isoleucine,
threonine, alanine, arginine and tyrosine) and ATP, and decreased the level of
glucose in male mussel hepatopancreas. In V. harveyi-challenged female mussel
hepatopancreas, both threonine and AMP were significantly elevated, and choline,
phoshphocholine, sn-glycero-3-phosphocholine, taurine, betaine and ATP were
depleted. Obviously, only threonine was similarly altered to that in V. harveyi
challenged male mussel hepatopancreas. These findings confirmed the gender
specific metabolic responses in mussels challenged by V. harveyi. Overall, V.
harveyi induced an enhanced energy demand through activated glycolysis and immune
response indicated by increased BCAAs in male mussel hepatopancreas. In female
mussel hepatopancreas, V. harveyi basically caused disturbances in both osmotic
regulation and energy metabolism through the metabolic pathways of conversions of
phosphocholine and ADP to choline and ATP, and sn-glycero-3-phosphocholine and
H2O into choline and sn-glycerol 3-phosphate. The altered mRNA expression levels
of related genes (Cu/Zn-SOD, HSP90, lysozyme and defensin) suggested that V.
harveyi induced obvious oxidative and immune stresses in both male and female
mussel hepatopancreas. This work demonstrated that V. harveyi could induce gender
specific metabolic responses in mussel M. galloprovincialis hepatopancreas using
NMR-based metabolomics.
PMID- 25123835
TI - The National Institutes of Health Physician-Scientist Workforce Working Group
report: a roadmap for preserving the physician-scientist.
PMID- 25123833
TI - Cloning and expression analysis of three novel CC chemokine genes from Japanese
flounder (Paralichthys olivaceus).
AB - Chemokines are small cytokines secreted by various cell types. They not only
function in cell activation, differentiation and trafficking, but they also have
influences on many biological processes. In this study, three novel CC chemokine
genes Paol-SCYA105, 106 and 107 in Japanese flounder (Paralichthys olivaceus)
were cloned and characterized. Paol-SCYA105 was mainly detected in gill, kidney
and spleen, Paol-SCYA106 was detected in all tissues examined and Paol-SCYA107
was mainly detected in the spleen and kidney. Paol-SCYA105 and Paol-SCYA106 gene
expressions peaked in kidney at day 3 after viral hemorrhagic septicemia virus
infection and decreased at day 6, but Paol-SCYA106 still remained at a high level
at day 6. Paol-SCYA107 gene expression was significantly up-regulated in kidney
at day 6 after viral hemorrhagic septicemia virus infection. In response to
infection by Gram-negative Edwardsiella tarda and Gram-positive Streptococcus
iniae in kidney, only Paol-SCYA106 gene expression significantly increased.
Together, these results indicate that these three novel CC chemokines are
involved in the immune response against pathogen infections.
PMID- 25123838
TI - The correlation of contrast-enhanced ultrasound and MRI perfusion quantitative
analysis in rabbit VX2 liver cancer.
AB - Our objective is to explore the value of liver cancer contrast-enhanced
ultrasound (CEUS) and MRI perfusion quantitative analysis in liver cancer and the
correlation between these two analysis methods. Rabbit VX2 liver cancer model was
established in this study. CEUS was applied. Sono Vue was applied in rabbits by
ear vein to dynamically observe and record the blood perfusion and changes in the
process of VX2 liver cancer and surrounding tissue. MRI perfusion quantitative
analysis was used to analyze the mean enhancement time and change law of maximal
slope increasing, which were further compared with the pathological examination
results. Quantitative indicators of liver cancer CEUS and MRI perfusion
quantitative analysis were compared, and the correlation between them was
analyzed by correlation analysis. Rabbit VX2 liver cancer model was successfully
established. CEUS showed that time-intensity curve of rabbit VX2 liver cancer
showed "fast in, fast out" model while MRI perfusion quantitative analysis showed
that quantitative parameter MTE of tumor tissue increased and MSI decreased: the
difference was statistically significant (P < 0.01). The diagnostic results of
CEUS and MRI perfusion quantitative analysis were not significantly different (P
> 0.05). However, the quantitative parameter of them were significantly
positively correlated (P < 0.05). CEUS and MRI perfusion quantitative analysis
can both dynamically monitor the liver cancer lesion and surrounding liver
parenchyma, and the quantitative parameters of them are correlated. The combined
application of both is of importance in early diagnosis of liver cancer.
PMID- 25123837
TI - Y-chromosome analysis in a Northwest Iberian population: unraveling the impact of
Northern African lineages.
AB - OBJECTIVES: To provide new clues about the genetic origin, composition and
structure of the population of the Spanish province of Zamora, with an emphasis
on the genetic impact of the period of Islamic rule in the Iberian Peninsula.
METHODS: Polymorphisms in the paternally inherited Y-chromosome, Single
Nucleotide Polymorphisms and Short Tandem Repeats, were analyzed in 235 unrelated
males born in six different regions in the Zamora province. RESULTS: A relatively
homogenous Y-chromosome haplogroup composition was observed in the Zamora
province. Haplogroups R1b1-P25 and I-M170, widespread in European populations,
accounted for 64.9% of the total sample. Moreover, all of the observed African
lineages, accounting for 10.2% of the total variability, belonged to haplogroups
having Northwest African origin (E1b1b1b-M81, E1b1b1a-beta-M78, and J1-M267).
CONCLUSIONS: No differences between regions or sub-structure due to geographical
boundaries were detected. The specific Northwest African male lineages observed
contrast with the mitochondrial DNA data, where the majority of African lineages
were found to be sub-Saharan. This work made it possible to study the impact of
recent historical events in the male gene pool in the province of Zamora in
Spain.
PMID- 25123839
TI - Effects of tirofiban on platelet activation and endothelial function in patients
with ST-elevation myocardial infarction undergoing primary percutaneous coronary
intervention.
AB - This pilot study examined, for the first time, the effect of intracoronary
administration of tirofiban, an inhibitor of platelet aggregation, on platelet
activation and endothelial dysfunction in patients with ST-segment-elevated
myocardial infarction (STEMI) undergoing percutaneous coronary intervention
(PCI). A total of 119 STEMI patients were randomized into either tirofiban group
(n = 72, intracoronary injection of 10 MUg/kg tirofiban prior to PCI, followed by
intravenous infusion at 0.15 MUg/kg min) or a control group (n = 47), which did
not receive tirofiban. Periprocedural administration of tirofiban was associated
with significantly reduced levels of platelet activation (lower levels of CD62P
and PAC-1) and endothelial dysfunction (reduced levels of endothelial
microparticles, VCAM-1, and ICAM-1) 48 h after PCI. At 10 days after PCI,
patients in the tirofiban group had a higher incidence of complete STR (78.7 vs.
65.0%) and higher left ventricular ejection fractions (47.8 vs. 44.2) compared to
those in the control group. The clinical outcomes between two groups did not
differ significantly two weeks after treatment. The results demonstrated that
periprocedural administration of tirofiban is associated with significantly
attenuated platelet activation and endothelial dysfunction in STEMI patients
undergoing PCI. This may have contributed to the improved myocardial reperfusion
and preservation of left ventricular systolic function in these patients.
PMID- 25123841
TI - Unraveling cell populations in tumors by single-cell mass cytometry.
AB - The development of new biotechnologies for the analysis of individual cells in
heterogeneous populations is an important direction of life science research.
This review provides a critical overview of relevant and recent advances in the
field of single-cell mass cytometry, focusing on the latest applications in the
study of cell heterogeneity. New approaches for multiparameter single-cell
imaging, alongside advanced computational tools for deep mining of high
dimensional mass cytometric data, are facilitating the visualization of specific
cell types and their interactions in complex cellular assemblies, such as tumors,
potentially revealing new insights into cancer biology.
PMID- 25123840
TI - Analysis of volatile organic compounds liberated and metabolised by human
umbilical vein endothelial cells (HUVEC) in vitro.
AB - Gas chromatography with mass spectrometric detection combined with head-space
needle trap extraction as the pre-concentration technique was applied to identify
and quantify volatile organic compounds released or metabolised by human
umbilical vein endothelial cells. Amongst the consumed species there were eight
aldehydes (2-methyl 2-propenal, 2-methyl propanal, 2-methyl butanal, 3-methyl
butanal, n-hexanal, benzaldehyde, n-octanal and n-nonanal) and n-butyl acetate.
Further eight compounds (ethyl acetate, ethyl propanoate, ethyl butyrate, 3
heptanone, 2-octanone, 2-nonanone, 2-methyl-5-(methylthio)-furan and toluene)
were found to be emitted by the cells under study. Possible metabolic pathways
leading to the uptake and release of these compounds by HUVEC are proposed and
discussed. The uptake of aldehydes by endothelial cells questions the reliability
of species from this chemical class as breath or blood markers of disease
processes in human organism. The analysis of volatiles released or emitted by
cell lines is shown to have a potential for the identification and assessment of
enzymes activities and expression.
PMID- 25123842
TI - Adaptive finite-time stabilization for a class of uncertain high order
nonholonomic systems.
AB - In this paper, the adaptive finite-time stabilization problem is investigated for
a class of high order nonholonomic systems in power chained form with strong
nonlinear drifts and nonlinear parameterization. By skillfully using finite-time
stability theorem, parameter separation technique and adding a power integrator
method, an adaptive state feedback controller is obtained. To overcome the
obstacle that x-subsystem is uncontrollable when the control input u0=0, a novel
switching control strategy is given. Based on this, the designed controller
renders that the states of closed-loop system are regulated to zero in a finite
time. Two illustrative examples are also provided to demonstrate the
effectiveness of the proposed controller.
PMID- 25123844
TI - Neurodevelopmental delays and macrocephaly in 17p13.1 microduplication syndrome.
AB - Microduplication of chromosome 17p13.1 is a rarely reported chromosome
abnormality associated with neurodevelopmental delays. We describe two unrelated
patients with overlapping microduplications of chromosome 17p13.1. The first
patient is a 2-year-old male who presented with neurodevelopmental delays and
macrocephaly. He was found to have a de novo 788 kb copy gain of 17p13.2p13.1 and
a de novo 134 kb copy gain of 17p13.1. These duplications include multiple
candidate genes, including EFNB3, NLGN2, DLG4, GABARAP, and DULLARD, which may be
responsible for neurodevelopmental delays in affected individuals. The second
patient is a 29-year-old female with mild intellectual disability and relative
macrocephaly. She was found to have a 62.5 kb copy gain of chromosome 17p13.1
that includes the DLG4, GABARAP, and DULLARD genes. The DLG4, GABARAP, and
DULLARD genes included in the microduplications of both our patients appear to be
candidate genes for neurodevelopmental delays and macrocephaly in individuals
with 17p13.1 microduplication syndrome.
PMID- 25123843
TI - Hypoalbuminaemia is associated with mortality in patients undergoing
cytoreductive nephrectomy.
AB - OBJECTIVE: To evaluate whether poor nutrition is associated with mortality in
patients undergoing cytoreductive nephrectomy (CN) for metastatic renal cell
carcinoma (mRCC). PATIENTS AND METHODS: A multi-institutional review of
prospective databases identified 246 patients meeting inclusion criteria who
underwent CN for mRCC from 1993 to 2012. Nutritional markers evaluated were: body
mass index <18.5 kg/m(2) , serum albumin <3.5 g/dL, or preoperative weight loss
of >=5% of body weight. Primary outcomes were overall (OS) and disease-specific
survival (DSS). Secondary outcome was 'early mortality' defined as death at <=6
months of surgery. Survival curves were estimated using the Kaplan-Meier product
limit method and multivariate analysis using logistic regression was used to test
associations between nutritional markers and survival outcomes. RESULTS: In all,
119 patients (median follow-up 17 months) were categorised as having any abnormal
nutrition parameter (48%). Hypoalbuminaemia was the only independent predictor of
OS and DSS (OS: median 8 vs 23 months, P < 0.001; DSS: 11 vs 33 months, P <
0.001). On multivariate analysis, hypoalbuminaemia remained a significant
predictor of death for both overall [hazard ratio (HR) 2, 95% confidence interval
(CI) 1.4-2.8; P < 0.001) and disease-specific mortality (HR 2.2, 95% CI 1.4-3.3;
P < 0.001). Hypoalbuminaemia was also associated with early mortality (overall: P
< 0.001 and disease specific: P = 0.002). CONCLUSION: Patients with mRCC and
hypoalbuminaemia undergoing CN have decreased OS and CSS, and increased risk of
all-cause and disease-specific early mortality. As such, serum albumin may help
risk stratify patients selected as candidates for CN. Furthermore, future work
should evaluate whether nutritional depletion is a modifiable risk factor.
PMID- 25123845
TI - Penta-O-galloyl-beta-D-glucose suppresses EGF-induced eIF3i expression through
inhibition of the PI3K/AKT/mTOR pathway in prostate cancer cells.
AB - Approximately 70% of prostate cancer patients will develop bone metastasis in
axial and other regions of the skeleton. Epidermal growth factor (EGF) generated
from bone tissue contributes to prostate cancer metastasis. In a previous study,
penta-O-galloyl-beta-D-glucose (PGG) suppressed androgen-independent prostate
cancer bone metastasis by transcriptionally repressing EGF-induced MMP-9
expression. This study utilized proteomics to analyze the effects of PGG in EGF
induced prostate cancer bone metastasis. This study showed that PGG suppressed
EGF-induced eIF3i expression in PC-3 cells. By transfection of eIF3i shRNA, it
was observed that reduced eIF3i expression suppressed the invasion of PC-3 cells
in vitro. PGG reduced EGF-induced eIF3i expression through inhibition of the
PI3K/AKT/mTOR pathway. Therefore, PGG may be able to be used as a potential new
therapeutic drug for prostate cancer bone metastasis.
PMID- 25123847
TI - Volatility of serum creatinine relative to tacrolimus levels predicts kidney
transplant rejection.
AB - BACKGROUND: We hypothesized that greater volatility of creatinine (SCr) relative
to tacrolimus levels [Tac] (VCT) is associated with an increased risk of
rejection. MATERIAL AND METHODS: Retrospective chart review was performed of all
single-kidney-only transplants in our Renal Transplant Program from March 2004 to
March 2010 (n=117) whose immunosuppressive regimen included tacrolimus (n=81). We
collected all available SCr and [Tac] over the first 2 years post-transplant and
calculated the VCT for each patient. SCr and [Tac] values were excluded from the
first month and from the rise that occurred immediately preceding a rejection
episode. RESULTS: Univariate analysis revealed that VCT was associated with
increased odds of biopsy-proven rejection. A logistic regression model including
donor type and HLA matches revealed that VCT (OR=1.16 [1.07, 1.26], p=0.0004) was
strongly associated with rejection. ROC curve analysis yielded an AUC=0.823
(p<0.0001). CONCLUSIONS: Increased volatility of SCr relative to [Tac] is
associated with an increased risk of rejection. Whereas increased variation in
[Tac] levels has been shown to indicate reduced adherence, increased VCT may
signal 'immunologic unrest' in the graft. Further studies are warranted to
determine if intervention at the time when volatility increases can lower the
risk of an acute rejection episode.
PMID- 25123849
TI - Polypyrrole-derived nitrogen and oxygen co-doped mesoporous carbons as efficient
metal-free electrocatalyst for hydrazine oxidation.
AB - We demonstrate that polypyrrole-derived nitrogen and oxygen co-doped mesoporous
carbons can serve as efficient, metal-free electrocatalysts for hydrazine
oxidation reaction, with low overpotential and high current density. The
materials' structures and the nature and type of their included dopants, which
can be controlled by varying the synthetic conditions, can affect the
electrocatalytic properties of the materials.
PMID- 25123848
TI - [60]Fullerene derivative modulates adenosine and metabotropic glutamate receptors
gene expression: a possible protective effect against hypoxia.
AB - BACKGROUND: Glutamate, the main excitatory neurotransmitter, is involved in
learning and memory processes but at higher concentration results excitotoxic
causing degeneration and neuronal death. Adenosine is a nucleoside that exhibit
neuroprotective effects by modulating of glutamate release. Hypoxic and related
oxidative conditions, in which adenosine and metabotropic glutamate receptors are
involved, have been demonstrated to contribute to neurodegenerative processes
occurring in certain human pathologies. RESULTS: Human neuroblastoma cells (SH
SY5Y) were used to evaluate the long time (24, 48 and 72 hours) effects of a
[60]fullerene hydrosoluble derivative (t3ss) as potential inhibitor of hypoxic
insult. Low oxygen concentration (5% O2) caused cell death, which was avoided by
t3ss exposure in a concentration dependent manner. In addition, gene expression
analysis by real time PCR of adenosine A1, A2A and A2B and metabotropic glutamate
1 and 5 receptors revealed that t3ss significantly increased A1 and mGlu1
expression in hypoxic conditions. Moreover, t3ss prevented the hypoxia-induced
increase in A2A mRNA expression. CONCLUSIONS: As t3ss causes overexpression of
adenosine A1 and metabotropic glutamate receptors which have been shown to be
neuroprotective, our results point to a radical scavenger protective effect of
t3ss through the enhancement of these neuroprotective receptors expression.
Therefore, the utility of these nanoparticles as therapeutic target to avoid
degeneration and cell death of neurodegenerative diseases is suggested.
PMID- 25123850
TI - Up-regulated expression of Dicer reveals poor prognosis in laryngeal squamous
cell carcinoma.
AB - CONCLUSIONS: Increased expression of Dicer may be a prognostic biomarker for
patients with laryngeal squamous cell carcinoma (LSCC). OBJECTIVES: Recent
studies have shown that many microRNAs (miRNAs) play an important role in the
development and progression of human cancers. Dicer, one of the most important
enzymes of the miRNA machinery, performs the final step of biogenesis of miRNAs.
This study aimed to investigate the impact of Dicer expression on patient
survival in human LSCC. METHODS: We detected the expression of Dicer in larynx
tissue specimens from 76 LSCC samples and 26 polyps by immunohistochemistry. The
clinicopathological and prognostic significance of Dicer expression was
investigated in LSCC. RESULTS: Our data showed that the expression of Dicer was
significantly higher in the LSCC than in the polyp tissue specimens. Moreover,
the expression level of Dicer was significantly associated with the pTNM stage
and tumor lymph node metastasis. Kaplan-Meier survival analyses revealed a strong
association between tumor Dicer expression and the survival of the patients with
LSCC.
PMID- 25123851
TI - Comparability of single measurements of serum testosterone to the 24-hour C(avg)
in patients using testosterone 2% solution.
AB - INTRODUCTION: Efficacy of testosterone replacement therapy is determined by the
proportion of men with 24-hour average serum testosterone concentration (Cavg )
in the normal range. In clinical practice, monitoring and dose adjustments are
based on single testosterone measurements; however, how single measurements
reflect Cavg is unclear. AIM: This post-hoc analysis evaluated whether single
serum testosterone measurements and Cavg from the same day are both in the normal
range in men receiving testosterone replacement therapy. METHODS: In an open
label, multicenter, titration trial, androgen-deficient men (N = 155) were
started on 60-mg daily morning dose of testosterone 2% solution (Axiron(r), Eli
Lilly and Company, Indianapolis, Indiana, USA) applied to axillae (30 mg/axilla).
Serum testosterone Cavg was determined on Days 15, 60, and 120. If necessary,
dose was adjusted to maintain Cavg in the normal range (300-1,050 ng/dL). This
analysis included subjects (n = 105) whose Cavg was within the normal range on
Days 15, 60, and 120. MAIN OUTCOME MEASURES: Proportion of men with normal serum
testosterone levels at 2, 4, or 8 hours post-dose on Days 15, 60, and 120.
RESULTS: Greater than 93% of subjects had testosterone serum levels within the
normal range 2, 4, or 8 hours post-dose on at least 1 day. In subjects with blood
samples available from Days 15 and 60 or Days 15 and 120, 71.1% to 79.8% had
normal levels at 2, 4, or 8 hours post-dose on both days, and in subjects with
blood samples available from Days 15, 60, and 120, 63.9% to 68.8% had normal
levels at 2, 4, or 8 hours post-application on all 3 days. CONCLUSION: Less than
70% of single testosterone measurements made on 3 separate days were concordant
with same-day Cavg for all 3 days. These findings, which are specific for
testosterone 2% solution, indicate that single measurements do not always reflect
the 24-hour Cavg , and may possibly lead to inappropriate dose adjustments.
PMID- 25123852
TI - The pros and cons of funnel plots as an aid to risk communication and patient
decision making.
AB - Funnel plots, which simultaneously display a sample statistic and the
corresponding sample size for multiple cases, have a range of applications. In
medicine, they are used to display treatment outcome rates and caseload volume by
institution, which can inform strategic decisions about health care delivery. We
investigated lay people's understanding of such plots and explored their
suitability as an aid to individual treatment decisions. In two studies, 172
participants answered objective questions about funnel plots representing the
surgical outcomes (survival or mortality rates) of institutions varying in
caseload, and indicated their preferred institutions. Accuracy for extracting
objective information was high, unless question phrasing was inconsistent with
the plot's survival/mortality framing, or participants had low numeracy levels.
Participants integrated caseload-volume and outcome-rate data when forming
preferences, but were influenced by reference lines on the plot to make
inappropriate discriminations between institutions with similar outcome rates.
With careful choice of accompanying language, funnel plots can be readily
understood and are therefore a useful tool for communicating risk. However, they
are less effective as a decision aid for individual patient's treatment
decisions, and we recommend refinements to the standard presentation of the plots
if they are to be used for that purpose.
PMID- 25123853
TI - 'The thieving magpie'? No evidence for attraction to shiny objects.
AB - It is widely accepted in European culture that magpies (Pica pica) are
unconditionally attracted to shiny objects and routinely steal small trinkets
such as jewellery, almost as a compulsion. Despite the long history of this
folklore, published accounts of magpies collecting shiny objects are rare and
empirical evidence for the behaviour is lacking. The latter is surprising
considering that an attraction to bright objects is well documented in some bird
species. The present study aims to clarify whether magpies show greater
attraction to shiny objects than non-shiny objects when presented at the same
time. We did not find evidence of an unconditional attraction to shiny objects in
either captive or free-living birds. Instead, all objects elicited responses
indicating neophobia in free-living birds. We suggest that humans notice when
magpies occasionally pick up shiny objects because they believe the birds find
them attractive, while it goes unnoticed when magpies interact with less eye
catching items. The folklore may therefore result from observation bias and
cultural inflation of orally transmitted episodic events.
PMID- 25123854
TI - [Neglected infectious diseases in the tropics].
PMID- 25123846
TI - A systematic review of causes of sudden and severe headache (Thunderclap
Headache): should lists be evidence based?
AB - BACKGROUND: There are many potential causes of sudden and severe headache
(thunderclap headache), the most important of which is aneurysmal subarachnoid
haemorrhage. Published academic reviews report a wide range of causes. We sought
to create a definitive list of causes, other than aneurysmal subarachnoid
haemorrhage, using a systematic review. METHODS: Systematic Review of EMBASE and
MEDLINE databases using pre-defined search criteria up to September 2009. We
extracted data from any original research paper or case report describing a case
of someone presenting with a sudden and severe headache, and summarized the
published causes. RESULTS: Our search identified over 21,000 titles, of which
1224 articles were scrutinized in full. 213 articles described 2345 people with
sudden and severe headache, and we identified 6 English language academic review
articles. A total of 119 causes were identified, of which 46 (38%) were not
mentioned in published academic review articles. Using capture-recapture
analysis, we estimate that our search was 98% complete. There is only one
population-based estimate of the incidence of sudden and severe headache at 43
cases per 100,000. In cohort studies, the most common causes identified were
primary headaches or headaches of uncertain cause. Vasoconstriction syndromes are
commonly mentioned in case reports or case series. The most common cause not
mentioned in academic reviews was pneumocephalus. 70 non-English language
articles were identified but these did not contain additional causes.
CONCLUSIONS: There are over 100 different published causes of sudden and severe
headache, other than aneurysmal subarachnoid haemorrhage. We have now made a
definitive list of causes for future reference which we intend to maintain. There
is a need for an up to date population based description of cause of sudden and
severe headache as the modern epidemiology of thunderclap headache may require
updating in the light of research on cerebral vasoconstriction syndromes.
PMID- 25123855
TI - [Leptospirosis seroprevalence and associated features in rice farmers of tropical
region of Peru].
AB - OBJECTIVES: To estimate the seroprevalence of leptospirosis in rice farmers of
the Alto Mayo Valley in the Peruvian region of San Martin and to identify factors
associated with infection. MATERIALS AND METHODS: A cross-sectional study was
conducted between October and November of 2010 on a sample of 254 farmers from
eleven irrigation committees in the Alto Mayo Valley. A blood sample was
collected as well as sociodemographic, household and labor characteristics in the
form of a questionnaire. The presence of antibodies against leptospira was
determined using the microscopic agglutination test and the IgM ELISA. RESULTS:
The seroprevalence by agglutination was 64.6% (95% CI: 58.6-70.6). The IgM ELISA
test was reactive in 15,0% (95% CI: 10.5-19.5). The most frequent serovar were
Icterohaemorrhagiae, Autumnalis, Australis, Panama and Grippotyphosa.
Independently associated factors were handling rodents (adjusted OR (aOR): 7.9;
95% CI: 1.6-37.9), working barefoot (aOR: 2.9; 95% CI: 1.2-6.8) and male sex
(aOR: 4.5; 95% CI: 1.3-15.3). CONCLUSIONS: The Alto Mayo Valley is a hyperendemic
for leptospirosis. The most important factors were associated with working
barefoot and handling rodents in crop fields. Consequently, it is recommended to
implement interventions that affect these two factors in order to reduce the risk
of infection in rice farmers.
PMID- 25123856
TI - [Prevalence of hepatitis B infection in children under 5 years old on indigenous
communities of the Peruvian Amazonia after immunization interventions].
AB - OBJECTIVES: To determine the prevalence of hepatitis B virus (HVB) infection and
seroprotection in indigenous children living in three draining basins of the
Peruvian Amazon. MATERIALS AND METHODS: A cross sectional study was conducted in
three draining basins (Pastaza, Morona and Lower Urubamba rivers), home to six
indigenous populations: shapra, candoshi, machiguenga, yine, ashaninka and nanti.
Children under 5 years were included. A survey and review of the vaccination card
was applied, and a serum sample was processed with ELISA for HBsAg, total anti
HBc and anti-HBs was obtained, defining "seroprotected children" if they were
reactive to anti-HBs and non-reactive to anti-HBc. RESULTS: A total of 742
children under 5 years old residents in six indigenous communities were included
in the study. 380 (51.2%) were male and 169 (22.9%) one year old or younger.
Regarding recorded HVB vaccination on the card, only 434 (58.5%) had received
three doses; 208 (38.8%) received the first dose within 24 hours. No cases were
detected with HBsAg. 88.8% of children had seroconverted, varying between 67-100%
across the populations. CONCLUSIONS: No cases of chronic HBV infection were
detected. The vaccination coverage by card revision is low, contrasting with high
seroconversion rates.
PMID- 25123857
TI - [Gestational syphilis and associated factors in public hospitals of Peru during
2000-2010].
AB - OBJECTIVES: To determine the epidemiological profile of gestational syphilis and
associated factors in a Peruvian population. MATERIALS AND METHODS: The study is
a secondary analysis of data obtained from public hospitals in Peru for the 2000
2010 period. 652,636 pregnant women were included from 37 cities and 45 health
centers in Peru. RESULTS: The prevalence of gestational syphilis was 0.7%, while
80.7% reported screening for gestational syphilis. The highest prevalence of
maternal syphilis is found in the lowland rainforest followed by the highland
rainforest. In the three regions of Peru decreased prevalence of gestational
syphilis has been seen throughout the years. The prevalence for 2010 are 0.2% on
the coast, in the highlands 0.23% and 0.47% in the jungle. The lack of education
and prenatal care, high parity, cohabiting or single, and living in the jungle,
are associated with having a positive syphilis test. CONCLUSIONS: The results
suggests that prevalence of gestational syphilis has declined over the decade
2000-2010.
PMID- 25123858
TI - [Comparing two protocols of DNA extraction of Trypanosoma cruzi cultured in
axenic medium].
AB - OBJECTIVES: To compare two extraction protocols of Trypanosoma cruzi DNA for use
in DNA amplification of kinetoplast minicircles (kDNA) through the technique of
Polymerase Chain Reaction (PCR). MATERIALS AND METHODS: Epimastigotes of T. cruzi
were cultured in axenic conditions and masses from 1.5 to 100 x 106 parasites
were obtained. DNA extraction was performed using two protocols: extraction with
organic solvents (phenol/chloroform), and with resin (Chelex100), from different
parasitic sediments. Concentration and purity of DNA was determined by
spectrophotometry, and integrity was assessed by agarose gel electrophoresis.
Analysis of variance and comparisons of means were performed through Tukey's
test, using the Statistix 8.0 software. RESULTS: Ten DNA extractions were done of
each one of the different amounts of parasitic sediments. In the DNA extraction
with Chelex100 resin, a higher performance was obtained but a lower purity and
integrity compared to the extraction with organic solvents. However, it allowed a
product amplification of 330 bp of T. cruzi kDNA. CONCLUSIONS: Although the
technique of Chelex100 provided less purity and integrity of DNA, it allowed a
successful amplification of kDNA by PCR, avoiding the use of laborious techniques
and toxic organic solvents.
PMID- 25123859
TI - [Neonatal mortality, analysis of surveillance registers, and neonatal medical
histories of 2011 in Huanuco and Ucayali, Peru].
AB - OBJECTIVES: To estimate the rate of neonatal mortality and to describe neonatal
deaths in 2011 in hospitals of the Ministry of Health at Huanuco and Ucayali
(Peru). MATERIALS AND METHODS: Cross-sectional study from September to November
2012 in Huanuco and Ucayali. Records of neonatal deaths in 2011 were reviewed
from provincial municipalities, regional health directorates and four referral
hospitals. To calculate mortality rates, we used the most reliable information
sources by region. Reviewing 185 medical records in hospitals allowed us to
describe the root causes of neonatal deaths. RESULTS: In 2011, 10,886 live births
and 158 neonatal deaths were reported in Huanuco, with a rate of 14.5 deaths per
1000 live births. In Ucayali, 11,441 live births and 138 neonatal deaths were
reported, with a rate of 12.1 deaths per 1000 live births. Most hospital neonatal
deaths occurred in the first 7 days of life (87%), in preterm infants (73.9%) and
with low birth weight (67%). The most common underlying causes of neonatal deaths
were infection (31.4%), congenital malformation (22.2%) and prematurity (18.9%).
CONCLUSIONS: Neonatal mortality rate in the studied regions was higher than the
national average. The results suggest the need for effective and comprehensive
interventions during pregnancy, childbirth and the early postnatal period; this
last period is the most vulnerable in the neonate.
PMID- 25123860
TI - [Prevalence and demographic factors associated with ferritin deficiency in
Colombian children, 2010].
AB - OBJECTIVES: To determine prevalence and socio-demographic factors associated with
ferritin deficiency in a representative sample of children in Colombia. MATERIALS
AND METHODS: Cross sectional secondary data analysis of the National Survey on
the Nutritional Situation (ENSIN) conducted in 2010 in Colombia in 3542 children
between 12 and 59 months. Plasma ferritin levels were determined by
chemiluminescence and values <12 ug/L were considered as deficit ferritin.
Sociodemographic factors (sex, age, ethnicity, socioeconomic status, and
geographical region) were collected using a structured questionnaire. All
analyses were performed taking into account the complex nature of the sample.
RESULTS: It was found that the average value of ferritin was 32.1 g/L, (CI 95%:
30.7-35.6).10.6% (CI 95%: 9.3-12.0) of the children had ferritin levels less than
12.0 ug/L. The multivariate logistic regression shows that children aged 12 to 23
(OR 5.1, CI 95%: 3.3-8.0) and 24 to 35 months (OR 2.4, CI 95%: 1.5-3.7),
belonging to the indigenous ethnic group (OR 1.8, CI 95%: 1.1-2.8), living in the
Atlantic region (OR 2.0, CI 95%: 1.1 -3.6), or Pacific area (OR 2.0, CI 95%: 1.1
3.6) were associated with a higher probability of ferritin deficiencies.
CONCLUSIONS: A significant prevalence of anemia caused by ferritin deficiency was
found as well as various sociodemographic factors that contributed to the
likelihood of increasing this problem. Comprehensive interventions are
recommended in which nutritional and educational components are involved.
PMID- 25123861
TI - [Evaluating maternal child care practices in extreme poverty areas in Peru,
2012].
AB - OBJECTIVES: To evaluate maternal and child care practices in areas with extreme
poverty in Peru. MATERIALS AND METHODS: Cross-sectional study conducted between
August and September 2012; with probabilistic, three-stage stratification by
"department" (geographic region) sampling. 540 households were selected that had
at least one child younger than 36 months (475 households) and/or a pregnant
women (80 households), in rural areas of Cajamarca, Amazonas, Huanuco, Ayacucho,
Huancavelica, Apurimac, Cusco, Puno and Ucayali. RESULTS: Regarding the last
pregnancy, 69.0% of the mothers reported having had their first prenatal care in
the first trimester; 65.3% reported having completed more than six check-ups
throughout the pregnancy; 81.1% reported having given birth in a health facility,
and only 31.0% chose a method of family planning within 42 days postpartum. With
regard to the last child under 3 years old, 64.1% had early mother-infant
contact, and 62.8% initiated breastfeeding within one hour of birth. In addition,
89.6% of children under 6 months old exclusively received breastfeeding and 89.1%
of children aged 6-8 months old already had received complementary feeding.
Fever, diarrhea, vomiting and breathing difficulty were the most mentioned
warning signs for seeking care for children. CONCLUSIONS: Through this study, a
baseline has been established on which a strategy can be designed and implemented
to improve best practices for maternal and child care as part of the "Programa de
Apoyo" within the Health Sector Reform.
PMID- 25123862
TI - [Study of correlation between diagnostic hypertriglyceridemic waist and metabolic
syndrome in adults in Trujillo, Peru].
AB - OBJECTIVES: To determine the correlation between hypertriglyceridemic waist
(HTGW) and metabolic syndrome (MS) in adults of Trujillo according to diagnostic
criteria. MATERIALS AND METHODS: Observational, prospective and cross-sectional
study with a sample of 500 adults in Trujillo, selected by probability sampling
and stratified by sex and age. Information on anthropometric measurements, blood
pressure and biochemical tests was collected; Criteria proposed by the ATP III
and Joint Interim Statement (JIS) for MS, as well as Gomez and JIS for HTGW were
applied. EPIDAT software was used to calculate Z test, Student t test and the
Kappa (k) with a confidence interval (CI) of 95%. RESULTS: Information regarding
239 men and 261 women were collected. The frequency of HTGW according to Gomez
criteria was 30% in the total sample, 29.7% in men and 30.3% women. According to
JIS criteria the frequency was 34% in the total sample, 38.1% in men and 30.3%
women. Metabolic Syndrome with JIS criteria had good agreement with HTGW
according to Gomez criteria with k = 0.63 and according to JIS criteria with k =
0.66. CONCLUSIONS: Good agreement was evidenced between the HTGW according to
Gomez and JIS criteria and MS according to JIS.
PMID- 25123863
TI - [Effect of extracts of Geranium ayavacense W. (Pasuchaca) on glycemia on rats
with experimental diabetes mellitus].
AB - OBJECTIVES: To determine if the lyophilized aqueous extract of Geranium
ayavacense (Pasuchaca) has any effect on glycemia in rats with experimental
diabetes mellitus. MATERIALS AND METHODS: Experimental diabetes was induced with
alloxan. Rats included in the study met the following criteria: glycemia greater
than 200 mg/dL post administration of alloxan, and with a weight greater than 200
g. Rats with experimental diabetes were divided into six groups of eight rats
each. Group I received 3 mL of distilled water (control); group II received
Geranium ayavacense 12.7 mg/kg; group III received Geranium ayavacense 100 mg/kg;
group IV received Geranium ayavacense 200 mg/kg; group V received Geranium
ayavacense 300 mg/kg; group VI received Geranium ayavacense 500 mg/kg. Basal
glycemia was determined. Glycemia evaluations were performed at the 1st, 3rd,
6th, 12th and 24th hour after administrating the different interventions.
RESULTS: Geranium ayavacense groups of 300 and 500 mg/kg decreased glycemia
significantly (p <0.01) in every hour assessed after administration of the
extract, when compared with the control group. Geranium ayavacense group of 300
mg/kg decreased their blood glucose 8.14; 10.68; 14.87; 19.36 and 23.7% in the
1st, 3rd, 6th, 12th and 24th hour respectively. CONCLUSIONS: Under experimental
conditions, the aqueous extract of Geranium ayavacense has hypoglycemic effects
in rats.
PMID- 25123864
TI - [Epidemiological profile of traffic-related disability in Peru, 2012].
AB - OBJECTIVES: To describe the epidemiological profile of people living with
disabilities due to traffic accidents (TA) in Peru. MATERIALS AND METHODS:
Secondary analysis of the National Survey Specialized on Disability (ENEDIS) of
2012 and an ecological analysis of TA records of the Ministry of Transportation
and Communications was done. RESULTS: Disability by traffic accidents (DAT) was
reported by 49,036 persons; 81.3% of whom live in urban areas. The most frequent
disability was limited locomotion and skill (77.4%), followed by visual
impairment (22.9%). Dependence for activities was reported in 44.7% of persons
with disabilities. The regions with the highest prevalence of TA have a higher
prevalence of disability by traffic accidents (Spearman coefficient: 0.426,
p=0.034). CONCLUSIONS: Most of disability due to TA is found in urban areas,
correspond to males and consist of persons in economically productive age. The
most common form of disability is in locomotion. Most of individuals do not
receive any form of rehabilitation, which accentuates health inequity related to
traffic accidents.
PMID- 25123865
TI - [Bartonella henselae in children with regional adenitis treated in a Peruvian
national hospital, 2012].
AB - In order to determine the frequency of seropositive cases of Bartonella henselae
in children with regional adenitis treated in a national hospital in Peru, a
cross-sectional study was conducted in 106 children with regional adenitis
greater than 1 cm in diameter. The sample was selected from patients aged 5-11
years seen at the National Institute of Child Health for acute onset of regional
adentitis, with more than five days of symptoms. B. henselae seropositivity was
defined by indirect immunofluorescence test. We found that 86 children (81.1%)
were positive for B.henselae. The median age of the patients was 7 years. In the
bivariate analysis, the following associated factors were found: aged 5 years,
history of fever, lymphadenopathy greater than 4 cm and reported contact with
cat. In conclusion, children with regional adenitis treated in this national
referral hospital showed a high frequency of positive serology for B. henselae.
PMID- 25123866
TI - [Specificity of the intradermal Montenegro test in patients infected by
Trypanosoma cruzi from different regions of Peru].
AB - In order to assess the specificity of the leishmanin skin test in Chagas disease
patients without clinical history of leishmaniasis, present or former. A sample
of 102 persons infected with Trypanosoma cruzi (14 acute cases with
parasitological diagnosis and 88 chronic cases) through the demonstration of IgG
antibodies by ELISA and indirect immunofluorescence (IIF) were evaluated with
leishmanin soluble antigen which contained Leishmania (Viannia) peruviana
concentration of 25-30 ug/mL. Only five people showed cutaneous hypersensitivity
reaction to the application of the antigen between hours 48 and 72. The
Leishmanin skin test evaluated was negative in 97 people infected with T. cruzi,
thus specificity of 95.1% was achieved. In conclusion, the intradermal Montenegro
test is a simple and effective diagnostic tool that also could be used to
discriminate infections by Leishmania or T. cruzi, in Peruvian geographic areas
where both parasites are present.
PMID- 25123867
TI - [Mutant alleles associated to chloroquine and sulfadoxine-pyrimethanime
resistance in Plasmodium falciparum of the Ecuador-Peru and Ecuador-Colombia
borders].
AB - The frequency of mutations in pfCRT and DHFR/DHPS genes of Plasmodium falciparum
associated with resistance to chloroquine and sulfadoxine-pyrimethamine was
evaluated in 83 strains from the districts of Esmeralda and Machala, located on
the borders of Ecuador-Peru and Ecuador-Colombia in 2002. Polymerase chain
reaction (PCR), conventional and its variants, was used. Mutations in the pfCRT
gene were found in more than 90% of the samples from Esmeralda and Machala. For
the DHFR gene, 90% of the strains were mutant samples from Esmeralda, 3 were
double mutations and 1 was a triple mutation. In Machala, 25% were simple mutant
forms and 75% mixed mutant forms (wild forms/mutant). In conclusion, resistance
to chloroquine has been fixed in strains carrying K76T pfCRT mutation, whereas
genetic imprinting for resistance to pyrimethamine is evolving, particularly in
the district of Esmeralda.
PMID- 25123868
TI - [Purification of antigenic fraction 27-28 kDa from the metabolic antigen from
metabolic secreted-excreted from Fasciola hepatica].
AB - Antigenic fractions of 27-28 kDa from Fasciola hepatica were purified by size
exclusion chromatography for use in the diagnosis of human fasciolosis. Excretion
and secretion antigens were obtained from living adult flukes collected from
sheep and cattle liver, and cultured in minimum essential medium. The reactivity
of the purified antigen and efficacy were assessed by immunoblot test using four
sera with human fascioliasis; four sera with other parasites, and two negative
sera. We conclude that the purified antigenic fractions do not cross-react with
other parasites by immunoblot. Therefore, purified proteins are considered as
potential candidates to be used for the diagnosis of human fascioliasis.
PMID- 25123869
TI - [Publication of research projects for certification as medical specialists at a
Peruvian university, 2007-2010].
AB - In order to determine the frequency of publication in a scientific journal of the
research projects done for medical specialty certification, a search was
conducted in Google Scholar, Pubmed, biomedical databases and Peruvian medical
society journals. These publications were research projects carried out by
medical residents graduated from the Faculty of Medicine at the Universidad
Peruana Cayetano Heredia, to obtain the certification of medical specialist. Of
351 medical residents graduated between the years 2007-2010, 199 (65.5%)
completed their research project and 47 (23.6%) published it in a scientific
journal. The "medicine" (non-surgical) specialty area had the highest frequency
of publications. All publications were in Spanish journals, the majority in
indexed journals in regional databases. We conclude that 23.6% of the research
projects for certification as medical specialists are published, most often in
low visibility journals.
PMID- 25123870
TI - [Assessment of dot blot tests and latex agglutination for cysticercosis
diagnostic in Peru].
AB - In order to evaluate dot blot tests and latex agglutination for the detection of
human cysticercosis with liquid antigen of Taenia solium cysticerci, 125 human
sera were used, of which 60 were from people with cysticercosis confirmed by
Western Blot, 45 with other parasitic diseases and 20 apparently healthy. The
optimal concentration of antigen to impregnate dot blot strips was 0.01 ug/uL,
and to impregnate the latex particles was 0.092 ug/uL. For the dot blot test, a
sensitivity of 100% and specificity of 87.7% was found. For latex agglutination,
a sensitivity of 93.3% and specificity of 89.2% was found. Both tests may be
useful and feasible to implement alternatives of serological diagnosis in
laboratories in endemic areas of Peru.
PMID- 25123871
TI - [Hematophagous bats as reservoirs of rabies].
AB - Rabies continues to be a challenge for public health authorities and a constraint
to the livestock industry in Latin America. Wild and domestic canines and vampire
bats are the main transmitter species and reservoirs of the disease. Currently,
variations observed in the epidemiological profile of rabies, where the species
of hematophagous bat Desmodus rotundus constitutes the main transmitting species.
Over the years, knowledge has accumulated about the ecology, biology and behavior
of this species and the natural history of rabies, which should lead to
continuous development of methods of population control of d. Rotundus as well as
prevention and diagnostic tools for rabies. Ecological relationships of this
species with other hematophagous and non-hematophagous bats is unknown, and there
is much room for improvement in reporting systems and surveillance, as well as
creating greater awareness among the farming community. Understanding the impact
of human-induced environmental changes on the rabies virus in bats should be
cause for further investigation. This will require a combination of field studies
with mathematical models and new diagnostic tools. This review aims to present
the most relevant issues on the role of hematophagous bats as reservoirs and
transmitters of the rabies virus.
PMID- 25123872
TI - [Historical review of the distribution of Anopheles (Nyssorhynchus) darlingi
(Diptera: Culicidae) in the Peruvian Amazon].
AB - Anopheles (Nyssorhynchus) darlingi has been reported since 1931 in border areas
of the department of Loreto, mainly along the borders with Brazil and Colombia.
In 1994, during an outbreak of malaria, An. darlingi was found in neighboring
towns to Iquitos. At present, its distribution has expanded considerably in
Loreto. This paper reviews literature available for all possible information on
the distribution of mosquitoes, particularly anopheline in the Amazon region of
the country, with special emphasis on An darlingi. Entomological collections were
also conducted in the departments of Madre de Dios and Ucayali in order to know
and verify the distribution of An. darlingi. At present, the distribution of the
species is confined to localities in southeastern Peru with Bolivia border towns,
in a town near the Abujao River in the department of Ucayali, and widely in the
northeastern region of the Amazon basin of Loreto in Peru.
PMID- 25123873
TI - [The road to elimination: an overview of neglected infectious diseases in Latin
America and the Caribbean].
AB - Neglected infectious diseases (NID) affect mainly isolated populations living in
isolation and in poor socioeconomic conditions. These diseases, by their chronic
and silent nature, often affect communities with a weak political voice. This
translates into very little attention or political priority; which is reflected
in minimal and insufficient preventive measures, monitoring and control. However,
there is evidence this situation is changing favorably in some countries of the
Americas. In recent years, several resolutions (official agreement of the member
countries of the Pan American Health Organization / World Health Organization
PAHO / WHO), regional and global agreements on public health; with a greater
commitment from the pharmaceutical industry, and other donors and international
partners in combination with the development and use of integrated action plans
have allowed countries to intensify public interventions to control these
diseases and thus achieve target elimination of NID. Onchocerciasis, lymphatic
filariasis, Chagas disease, leprosy and trachoma blindness, among others, have
been eliminated in several countries and endemic areas, regardless of the level
of development of the country or geographical area where they are located. The
political decision reflected in adequate financial resources in the next decade
will be crucial to achieving the goals of elimination of NID (regional and
national).
PMID- 25123874
TI - [Neglected infectious diseases: an ongoing challenge for public health and equity
in Peru].
AB - Neglected Infectious Diseases (NID) affect more than one billion people
worldwide, and are associated with poverty, geographic isolation of populations,
social stigma, lack of precise data on estimates on both the global and local
burden of disease (underreporting of the diseases), inadequate financial and
political resources to effective control measures, lack of lobbying on behalf of
the most vulnerable population, as well as scarce drug and diagnostic methods
development. In this article we describe the relationship between NID, poverty
and inequality, we propose a new concept of disease in the tropics, expanding the
list of diseases that share characteristics with NID in the Peruvian context,
discuss the limited availability of drugs and diagnostic tests to properly deal
with these diseases, as well as highlight the contributions by the Peruvian
National Institute of Health, and as final thoughts, we state that the solution
for the prevention and control of NID must include an integrated approach,
including the social determinants of health in the context of the fight against
poverty and inequality.
PMID- 25123875
TI - [Critical appraisal about control programs and elimination of leprosy in Peru,
and its consequences for Peru and America].
AB - A critical analysis of health control measures that historically took place in
Peru to the present which has led Peru to officially consider leprosy as an
"eliminated" public health problem. We will also discuss the validity of the
status given the neglect of health surveillance, disbanded specialized control
entities, health medical staff forgetting to account for leprosy in early stages,
the presence of undiagnosed smear-positive leprosy in Lima and the undeniable
hidden prevalence, suggest that there is a danger to the country and the region
that a re-emergence of leprosy will occur, if relevant and appropriate sanitary
measures are not taken.
PMID- 25123876
TI - [Urbanization of Chagas disease in Peru: experiences in prevention and control].
AB - In Peru, Chagas disease has an epidemiological significance in three macro
regions, one of them is the southern macro-region formed by the departments of
Arequipa, Moquegua and Tacna. In 1965 a successful control was performed by house
spraying insecticides, however, the persistence of the vector made it necessary
for a second control plan that was implemented in 2000 and followed the
guidelines of CONAL Plan, based on the elimination of Triatoma infestans and
screening in blood banks.This plan was successful in Tacna and Moquegua,
therefore these departments were considered free of vectorial transmission by the
Pan American Health Organization. A ssimilar situation has not been achieved in
the department of Arequipa because of the presence, among other factors, of rural
migration to the city, in this way the urbanization of Chagas disease is a new
epidemiological scenario of which we need to know more.
PMID- 25123877
TI - [Experiences in the prevention and control of Carrion's disease in Peru].
AB - Carrion's disease, the iconic disease in Peruvian medicine has been found in the
mountains of Ecuador, Colombia and the Andean valleys of Peru. In the 1990s, the
phenomenon of El Nino was associated with significantly increased risk of disease
in Ancash, Cajamarca and Cusco. In Cusco in 1998 there was an acute phase
epidemic in various Andean provinces and the jungle area. Between 2001 and 2005
the disease has spread or reactivated in different regions such as Ancash,
Cajamarca, Amazonas, Piura, Cusco, La Libertad, Puno, and Ayacucho. In 2004 a
major outbreak of the disease in all of Peru was presented, reporting more than
11 164 cases, and therefore diverse strategies based vector susceptibility
studies was applied, lowering significantly the number of cases.
PMID- 25123878
TI - [Sporotrichosis and paracoccidioidomycosis in Peru: experiences in prevention and
control].
AB - The epidemiological picture of sporotrichosis and paracoccidioidomycosis in Peru
and Latin America is sporadic, fragmented, and geographically limited, mainly due
to lack of mandatory reporting and limited diagnostic coverage. However, research
contributions related to understanding the interaction of these fungi, the
response of the host and the environment, the use of spatial analysis that
relates the distribution of these mycoses, population density and climate,
contributes to the design of prevention and control strategies of these mycosis
and suggest epidemiological risk maps management, based on the habitat of the
fungus. This information will be used by doctors, tourists and people living in
rural areas where mycoses are endemic. The aim of the paper is to present a
review of the topic through research findings that contribute to the prevention
and control of these mycosis.
PMID- 25123880
TI - [Creutzfeldt-Jakob disease in Peru: report of eleven cases].
AB - Creutzfeldt-Jakob disease (CJD) is a fatal neurological disease caused by
pathological isoform of the human prion protein. Clinical features of six cases
of the sporadic form of CJD with definitive diagnosis by histopathology, and five
cases with probable diagnosis were reported in patients treated at the Peruvian
National Institute of Neurological Sciences. The average age of onset in definite
cases was 55.8 years and in probable cases was 59.6, mostly males. The average
disease duration was 8.8 months. A typical EEG was found in 50% of definite cases
and in 80% of probable. The 14-3-3 protein in cerebrospinal fluid was positive in
a probable case, and typical MRI findings were observed in two probable cases.
All cases studied had a typical clinical course of the disease, and it is
considered as the first report of CJD in Peru.
PMID- 25123881
TI - [Disseminated cysticercosis: report of a case in Peru].
AB - Cysticercosis is a neglected and endemic disease in Peru that commonly affects
the central nervous system (CNS), causing neurocysticercosis (NCC). However, only
a few reports of disseminated cysticercosis (DCC) exist in the world. In this
article we present a case report of a male, 82 year old patient from the
department of Junin (Peru). He presented a sudden loss of consciousness
associated with generalized tonic-clonic seizures. CT scan and brain MRI showed
multiple cystic lesions with scolex presence inside and compatible with massive
NCC. Thoracic, abdominal and pelvic MRI showed multi-organ dissemination of
cysticerci. Although there is little therapeutic experience in cases of DCC, the
patient received deworming treatment with albendazole and corticoids, in this way
a favorable clinical outcome was achieved without complications during
hospitalization.
PMID- 25123879
TI - [Unifying criteria for late neonatal sepsis: proposal for an algorithm of
diagnostic surveillance].
AB - Infections are a major cause of death in neonates. Diagnosis of neonatal sepsis
is a major challenge because newborns have very nonspecific clinical signs and
auxiliary tests have low sensitivity. In order to improve the correct diagnosis
of this condition, we propose an algorithm of diagnostic surveillance for late
neonatal sepsis in Peru and countries of the region. The algorithm classifies the
episodes as confirmed, probable or possible sepsis, and especially seeks to
identify those episodes that do not correspond to sepsis, preventing other
diseases to be qualified as "sepsis". Better diagnostics will enable more
realistic rates of neonatal sepsis, improve the use of antibiotics and avoid
their negative effects on newborns, as well as provide a more accurate view of
their impact on public health.
PMID- 25123882
TI - [Acute arterial occlusion associated disseminated hydatidosis].
AB - Hydatidosis or echinococcosis are terms used to denote the zoonotic infestation
caused by adult and larval stages (metacestode) of the cestode from the genus
Echinococcus (family tenidae). The term hydatidosis should be applied to the
infestation caused by the metacestode while echinococcosis for the larval and
adult stages. In Peru there is a high prevalence of this infection, liver and
lung being the most affected organs. There are factors from the host and from the
infectious agent that contribute to this infection, with the immune component of
the host as an important infection and dissemination point. A case of acute
arterial occlusion associated with disseminated hydatidosis in a 54 years old
patient, born and from Huancavelica, with sudden onset of an acute arterial
obstruction is reported. The patient did not improve after surgery and died
within 48 hours of presentation.
PMID- 25123883
TI - [Carrion's disease complicated with severe acute leptospirosis: a case report].
AB - The case of an adult, 56 year old male is reported, from Sihuas (Ancash) who
presented at Hospital Nacional Dos de Mayo with fever, jaundice and anemia. In
three days of hospitalization, he developed severe anemia (Hb: 11.8 to 6.7 g /
dL) and generalized myalgias associated with a sudden worsening jaundice
correlated with elevated bilirubin (TB 3.2 to 19.6 mg / dL direct dominance) and
general deterioration. Microbiological smear and culture were positive for
Bartonella bacilliformis. Subsequent serology (microagglutination) was positive
for Lesptospira serovar Pomona. The patient was given specific antibiotic therapy
(ceftriaxone and ciprofloxacin), transfused two units of packed red blood cells,
improved clinically and was discharged.
PMID- 25123884
TI - [Human bartonellosis: before and after Daniel Alcides Carrion].
AB - This is a review of bibliographic aspects associated to the knowledge about human
bartonelosis before and after the death of Daniel Alcides Carrion. Emphasis is
placed on stimulus in the development of medical research in Peru by the self
inoculation and subsequent death of Carrion especially in relation to human
bartonellosis, conducted by Peruvian researchers and others around the world. The
review includes the basic area of knowledge about the bacteria that causes the
illness, the host response to infection as well as the biphasic behavior of the
disease. The revised bibliography includes contributions to the knowledge of the
disease in the last 100 years, now known with the eponym "Carrion's disease".
PMID- 25123885
TI - [Life cycle of Strongyloides fuelleborni: images and videos].
PMID- 25123886
TI - [Financing for rare or orphan diseases: a thing to do].
PMID- 25123887
TI - [Monge's disease: a forgotten eponym?].
PMID- 25123888
TI - [Epidemiological surveillance, molecular biology and dengue 5].
PMID- 25123889
TI - [Scientific production of members of the National Academy of Sciences].
PMID- 25123890
TI - [Tuberculosis and diabetes comorbidity in a hospital of Colombia].
PMID- 25123891
TI - [Environmental health in Peru].
PMID- 25123892
TI - [Analysis of complex survey in population data].
PMID- 25123893
TI - [Stroke in Peru: a forgotten and unattended prevalent disease].
PMID- 25123894
TI - Direct hydrogenation of biomass-derived butyric acid to n-butanol over a
ruthenium-tin bimetallic catalyst.
AB - Catalytic hydrogenation of organic carboxylic acids and their esters, for
example, cellulosic ethanol from fermentation of acetic acid and hydrogenation of
ethyl acetate is a promising possibility for future biorefinery concepts. A
hybrid conversion process based on selective hydrogenation of butyric acid
combined with fermentation of glucose has been developed for producing
biobutanol. ZnO-supported Ru-Sn bimetallic catalysts exhibits unprecedentedly
superior performance in the vapor-phase hydrogenation of biomass-derived butyric
acid to n-butanol (>98% yield) for 3500 h without deactivation.
PMID- 25123896
TI - Have the New GP Contract and NICE guidelines improved the clinical care of people
with epilepsy?
AB - PURPOSE: This retrospective audit was to assess the effect of the New General
Practitioner (GP) Contract and National Institute for Health and Care Excellence
(NICE) guidelines on the care and management of people with epilepsy (PWE) during
the period of observation from April 2004 to April 2009. METHOD: The case notes
of 540 people on anti-epilepsy drugs (AEDs) aged 16 years were reviewed in 13
general practices serving Ellesmere Port and Neston. RESULTS: Forty-nine percent
of people with poorly controlled epilepsy were not under shared care. Diagnostic
doubt existed in 25 (5%) people. There was no evidence that the original
diagnosis had been actively reviewed by the GP in any case. There were 98 (18%)
women of childbearing age, in 21 of whom there was no evidence of pre-conceptual
counselling ever having taken place, and 61 (62%) were not receiving folic acid
routinely. Thirty-nine (7%) people were demonstrably non-compliant, whilst 74
(14%) people had prescription anomalies consisting mainly of inappropriate multi
dose regimens. CONCLUSION: Despite marked improvements in review rates after the
introduction of the New GP Contract five years previously, there are still
significant unmet needs in this patient group. Clinical Commissioning Groups
(CCGs) should consider funding an intermediate tier of care incorporating GPs
with a special interest in epilepsy (GPwSIes) and Epilepsy Nurse Specialists
(ENS) for PWE to improve and maintain existing and future primary care, as
epilepsy is phased out of the Quality and Outcomes Framework (QOF).
PMID- 25123895
TI - Cloning and expression of A. oryzae beta-glucosidase in Pichia pastoris.
AB - A beta-glucosidase gene (bgl) from Aspergillus oryzae GIF-10 was cloned,
sequenced and expressed. Its full-length DNA sequence was 2,903 bp and included
three introns. The full-length cDNA sequence contained an open reading frame of
2,586 nucleotides, encoding 862 amino acids with a potential secretion signal.
The A. oryzae GIF-10 bgl was functionally expressed in Pichia pastoris. After 7
day induction, protein yield reached 321 mg/mL. Using salicin as the substrate,
the specific activity of the purified enzyme reached 215 U/mg. The purified
recombinant beta-glucosidase was a 110-kDa glycoprotein with optimum catalytic
activity at pH 5.0 and 50 degrees C. The enzyme was stable between 20 and 60
degrees C, and retained 65% of its activity after being held at 60 degrees C for
30 min. The recombinant beta-glucosidase was relatively stable in a broad range
of pHs, from 4.0 to 6.5. It showed broad specific activity, hydrolyzing a range
of (1-4)-beta-diglycosides and (1-4)-alpha-diglycosides, and Mn(2+) stimulated
its activity significantly.
PMID- 25123897
TI - Can the syndrome of transient epileptic amnesia be the first feature of
Alzheimer's disease?
PMID- 25123898
TI - MindTheGap: integrated detection and assembly of short and long insertions.
AB - MOTIVATION: Insertions play an important role in genome evolution. However, such
variants are difficult to detect from short-read sequencing data, especially when
they exceed the paired-end insert size. Many approaches have been proposed to
call short insertion variants based on paired-end mapping. However, there remains
a lack of practical methods to detect and assemble long variants. RESULTS: We
propose here an original method, called MindTheGap, for the integrated detection
and assembly of insertion variants from re-sequencing data. Importantly, it is
designed to call insertions of any size, whether they are novel or duplicated,
homozygous or heterozygous in the donor genome. MindTheGap uses an efficient k
mer-based method to detect insertion sites in a reference genome, and
subsequently assemble them from the donor reads. MindTheGap showed high recall
and precision on simulated datasets of various genome complexities. When applied
to real Caenorhabditis elegans and human NA12878 datasets, MindTheGap detected
and correctly assembled insertions >1 kb, using at most 14 GB of memory.
PMID- 25123899
TI - NetComm: a network analysis tool based on communicability.
AB - MOTIVATION: Set-based network similarity metrics are increasingly used to
productively analyze genome-wide data. Conventional approaches, such as mean
shortest path and clique-based metrics, have been useful but are not well suited
to all applications. Computational scientists in other disciplines have developed
communicability as a complementary metric. Network communicability considers all
paths of all lengths between two network members. Given the success of previous
network analyses of protein-protein interactions, we applied the concepts of
network communicability to this problem. Here we show that our communicability
implementation has advantages over traditional approaches. Overall, analyses
suggest network communicability has considerable utility in analysis of large
scale biological networks. AVAILABILITY AND IMPLEMENTATION: We provide our method
as an R package for use in both human protein-protein interaction network
analyses and analyses of arbitrary networks along with a tutorial at
http://www.shawlab.org/NetComm/.
PMID- 25123900
TI - READemption-a tool for the computational analysis of deep-sequencing-based
transcriptome data.
AB - RNA-Seq has become a potent and widely used method to qualitatively and
quantitatively study transcriptomes. To draw biological conclusions based on RNA
Seq data, several steps, some of which are computationally intensive, have to be
taken. Our READemption pipeline takes care of these individual tasks and
integrates them into an easy-to-use tool with a command line interface. To
leverage the full power of modern computers, most subcommands of READemption
offer parallel data processing. While READemption was mainly developed for the
analysis of bacterial primary transcriptomes, we have successfully applied it to
analyze RNA-Seq reads from other sample types, including whole transcriptomes and
RNA immunoprecipitated with proteins, not only from bacteria but also from
eukaryotes and archaea. AVAILABILITY AND IMPLEMENTATION: READemption is
implemented in Python and is published under the ISC open source license. The
tool and documentation is hosted at http://pythonhosted.org/READemption
(DOI:10.6084/m9.figshare.977849).
PMID- 25123901
TI - gCUP: rapid GPU-based HIV-1 co-receptor usage prediction for next-generation
sequencing.
AB - SUMMARY: Next-generation sequencing (NGS) has a large potential in HIV
diagnostics, and genotypic prediction models have been developed and successfully
tested in the recent years. However, albeit being highly accurate, these
computational models lack computational efficiency to reach their full potential.
In this study, we demonstrate the use of graphics processing units (GPUs) in
combination with a computational prediction model for HIV tropism. Our new model
named gCUP, parallelized and optimized for GPU, is highly accurate and can
classify >175 000 sequences per second on an NVIDIA GeForce GTX 460. The
computational efficiency of our new model is the next step to enable NGS
technologies to reach clinical significance in HIV diagnostics. Moreover, our
approach is not limited to HIV tropism prediction, but can also be easily adapted
to other settings, e.g. drug resistance prediction. AVAILABILITY AND
IMPLEMENTATION: The source code can be downloaded at http://www.heiderlab.de
CONTACT: d.heider@wz-straubing.de.
PMID- 25123902
TI - Cross-validation under separate sampling: strong bias and how to correct it.
AB - MOTIVATION: It is commonly assumed in pattern recognition that cross-validation
error estimation is 'almost unbiased' as long as the number of folds is not too
small. While this is true for random sampling, it is not true with separate
sampling, where the populations are independently sampled, which is a common
situation in bioinformatics. RESULTS: We demonstrate, via analytical and
numerical methods, that classical cross-validation can have strong bias under
separate sampling, depending on the difference between the sampling ratios and
the true population probabilities. We propose a new separate-sampling cross
validation error estimator, and prove that it satisfies an 'almost unbiased'
theorem similar to that of random-sampling cross-validation. We present two case
studies with previously published data, which show that the results can change
drastically if the correct form of cross-validation is used. AVAILABILITY AND
IMPLEMENTATION: The source code in C++, along with the Supplementary Materials,
is available at: http://gsp.tamu.edu/Publications/supplementary/zollanvari13/.
PMID- 25123903
TI - HapMuC: somatic mutation calling using heterozygous germ line variants near
candidate mutations.
AB - MOTIVATION: Identifying somatic changes from tumor and matched normal sequences
has become a standard approach in cancer research. More specifically, this
requires accurate detection of somatic point mutations with low allele
frequencies in impure and heterogeneous cancer samples. Although haplotype
phasing information derived by using heterozygous germ line variants near
candidate mutations would improve accuracy, no somatic mutation caller that uses
such information is currently available. RESULTS: We propose a Bayesian
hierarchical method, termed HapMuC, in which power is increased by using
available information on heterozygous germ line variants located near candidate
mutations. We first constructed two generative models (the mutation model and the
error model). In the generative models, we prepared candidate haplotypes,
considering a heterozygous germ line variant if available, and the observed reads
were realigned to the haplotypes. We then inferred the haplotype frequencies and
computed the marginal likelihoods using a variational Bayesian algorithm.
Finally, we derived a Bayes factor for evaluating the possibility of the
existence of somatic mutations. We also demonstrated that our algorithm has
superior specificity and sensitivity compared with existing methods, as
determined based on a simulation, the TCGA Mutation Calling Benchmark 4 datasets
and data from the COLO-829 cell line. AVAILABILITY AND IMPLEMENTATION: The HapMuC
source code is available from http://github.com/usuyama/hapmuc.
PMID- 25123904
TI - Cordova: web-based management of genetic variation data.
AB - Cordova is an out-of-the-box solution for building and maintaining an online
database of genetic variations integrated with pathogenicity prediction results
from popular algorithms. Our primary motivation for developing this system is to
aid researchers and clinician-scientists in determining the clinical significance
of genetic variations. To achieve this goal, Cordova provides an interface to
review and manually or computationally curate genetic variation data as well as
share it for clinical diagnostics and the advancement of research. AVAILABILITY
AND IMPLEMENTATION: Cordova is open source under the MIT license and is freely
available for download at https://github.com/clcg/cordova.
PMID- 25123905
TI - SCDFinder, a web-based tool for the identification of putative novel ATM and ATR
targets.
AB - MOTIVATION: The S/TQ cluster domain (SCD) constitutes a new type of protein
domain that is not defined by sequence similarity but by the presence of multiple
S/TQ motifs within a variable stretch of amino acids. SCDs are recognized targets
for DNA damage response (DDR) kinases like ATM and ATR. Characterizing DDR
targets is of significant interest. The aim of this work was to develop a web
based tool to allow for easy identification and visualization of SCDs within
specific proteins or in whole proteome sets, a feature not supported by current
domain and motif search tools. RESULTS: We have developed an algorithm that (i)
generates a list of all proteins in an organism containing at least one user
defined SCD within their sequence, or (ii) identifies and renders a visual
representation of all user-defined SCDs present in a single sequence or batch of
sequences. AVAILABILITY AND IMPLEMENTATION: The application was developed using
Pearl and Python, and is available at the following URL:
http://ustbioinfo.webfactional.com/scd/.
PMID- 25123906
TI - Response to: Reflections on competency-based education and training for surgical
residents.
PMID- 25123908
TI - The power of approximate degrees of freedom tests in heteroscedastic factorial
designs.
AB - Several viable approaches have been proposed for conducting factorial analysis
when the homogeneous variances assumption is violated. Although robust type I
error control and excellent power performance are desirable properties of a test
procedure for making statistical inferences, the corresponding power calculations
must also be considered to extend its applicability in planning research studies.
This article presents the power functions of two approximate degrees of freedom
tests within the context of two-way factorial designs. Both theoretical
examination and empirical investigation are performed to demonstrate the
underlying features of the two approaches. Simulation results showed that the
suggested procedures provide remarkably good approximations over a wide range of
model configurations. In view of the overall accuracy, the power functions are
recommended for enhancing the usefulness of the associated test procedures. To
facilitate the adoption of the suggested methodology in factorial research
designs, computer code is presented for implementing the described power
calculations.
PMID- 25123907
TI - Letter to the editor response.
PMID- 25123909
TI - POLYMAT-C: a comprehensive SPSS program for computing the polychoric correlation
matrix.
AB - We provide a free noncommercial SPSS program that implements procedures for (a)
obtaining the polychoric correlation matrix between a set of ordered categorical
measures, so that it can be used as input for the SPSS factor analysis (FA)
program; (b) testing the null hypothesis of zero population correlation for each
element of the matrix by using appropriate simulation procedures; (c) obtaining
valid and accurate confidence intervals via bootstrap resampling for those
correlations found to be significant; and (d) performing, if necessary, a
smoothing procedure that makes the matrix amenable to any FA estimation
procedure. For the main purpose (a), the program uses a robust unified procedure
that allows four different types of estimates to be obtained at the user's
choice. Overall, we hope the program will be a very useful tool for the applied
researcher, not only because it provides an appropriate input matrix for FA, but
also because it allows the researcher to carefully check the appropriateness of
the matrix for this purpose. The SPSS syntax, a short manual, and data files
related to this article are available as Supplemental materials that are
available for download with this article.
PMID- 25123910
TI - Magnetic resonance imaging-based diagnosis of progressive multifocal
leukoencephalopathy in a patient with non-Hodgkin lymphoma after therapy with
cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab.
PMID- 25123911
TI - Reply to Luzzatto et al. (2014): "Comment on 'Genetic evidence and new
morphometric data as essential tools to identify the Patagonian seahorse
Hippocampus patagonicus (Pisces, Syngnathidae), Gonzalez et al. (2014)'".
PMID- 25123912
TI - Surface free energy of the human skin and its critical surface tension of wetting
in the skin/surfactant aqueous solution/air system.
AB - BACKGROUND/PURPOSE: The purpose of these studies was to determine the surface
free energy of the human skin and its critical surface tension of wetting in the
skin--surfactant aqueous solution--air system in relation to different types of
surfactants. METHODS: The surface free energy of the skin and its components was
calculated using the equilibrium advancing contact angle values of water,
formamide, and diiodomethane on the forearm skin surface. Next, taking into
account the measured values of the contact angle of aqueous solutions of SDDS,
CTAB, TX-100 and TX-114 on the skin surface and data of their surface tension,
the critical surface tension of the skin wetting was determined. RESULTS: We can
classify the skin surface as low-energetic one. The critical surface tension of
the skin wetting depends on the type of surfactant. CONCLUSION: It is possible to
determine the critical surface tension of the human skin wetting on the basis of
the values of the contact angle of aqueous solutions of surfactants and their
surface tension. In this respect, nonionic surfactants seem to be the most
appropriate.
PMID- 25123920
TI - The chloridomolybdenum(III) cluster in [BMIm]4[AgMo10Cl35] with infinite chains
of Ag(+)-linked [Mo10Cl35](5-) wheels.
AB - [BMIm]4[AgMo10Cl35] is prepared by reaction of MoCl5 and elemental silver in the
ionic liquid [BMIm][AlCl4] ([BMIm(+)]: 1-butyl-4-methylimidazolium).
Surprisingly, elemental silver is oxidized under these conditions. The title
compound contains a new wheel-shaped [Mo10Cl35](5-) chlorido molybdenum(iii)
species with five pairs of Mo-Mo bonds. The Mo-Mo distances are found to be 263
pm on average. The [Mo10Cl35](5-) wheels exhibit a maximum opening of 558 pm in
diameter. They are interlinked via Ag(+) to form infinite [AgMo10Cl35](4-)
chains. The title compound is characterized by single crystal structure analysis,
EDX, FT-IR and UV-Vis spectroscopy. The wheel-type structure and Ag(+) linkage to
infinite chains are a new aspect of halogenido metalates and low-valence
molybdenum compounds.
PMID- 25123919
TI - A simple technique for reconstruction of medial patellofemoral ligament with bone
fascia tunnel fixation at the medial margin of the patella: a 6-year-minimum
follow-up study.
AB - BACKGROUND: Medial patellofemoral ligament (MPFL) reconstruction has become an
accepted technique to treat patellofemoral instability, and numerous surgical
techniques have been described to reconstruct the MPFL. We describe a MPFL
reconstruction procedure where bone-fascia tunnel fixation occurs at the medial
margin of the patella for recurrent patellar dislocation. OBJECTIVE: MPFL
reconstruction is the preferred operative treatment for recurrent patellar
dislocation. The purpose of this study was to report a simple technique for
reconstruction of medial patellofemoral ligament with bone-fascia tunnel fixation
at the medial margin of the patella for recurrent patellar dislocation and to
evaluate the results at 6-year-minimum follow-up. METHODS: The study included 65
patients (28 males, 37 females; mean age, 29.4 +/- 5.6 years) who underwent MPFL
reconstruction using the bone-fascia tunnel fixation at the medial margin of the
patella technique and who were followed for a mean duration of 78.5 +/- 3.8
months. Objective assessment, Kujala scale, Lysholm score, and Tegner activity
score were obtained preoperatively and at the time of final follow-up. RESULTS:
There were no patellar complications, including redislocation, in the present
study. The congruence angle had significant improvement from 19.2 degrees +/-
6.3 degrees before surgery to -6.03 degrees +/- 0.50 degrees at the last
follow-up. The lateral patellar angle had significant improvement from -6.9
degrees +/- 3.5 degrees before surgery to 5.1 degrees +/- 2.4 degrees at the
last follow-up. The patellar tilt angle had significant improvement from 24.5
degrees +/- 5.2 degrees before surgery to 12.30 degrees +/- 1.90 degrees at
the last follow-up. The Kujala score was significantly increased from 52.9 +/-
3.2 points preoperatively to 90.1 +/- 5.8 points postoperatively (P < 0.05). The
mean Lysholm score was significantly increased from 47.2 +/- 5.2 to 92.5 +/- 6.2
points postoperatively (P < 0.05). The Tegner activity score improved overall
from 3.1 +/- 0.6 points to 5.8 +/- 0.9 points at follow-up. CONCLUSION: We have
done a simple technique where the MPFL is reconstructed safely to avoid patella
fracture, anatomically to restore physiological kinematics and stability, and
economically to reduce costs with bone-fascia tunnel fixation at the medial
margin of the patella.
PMID- 25123918
TI - Genetic architecture of ALS in Sardinia.
AB - Conserved populations, such as Sardinians, displaying elevated rates of familial
or sporadic amyotrophic lateral sclerosis (ALS) provide unique information on the
genetics of the disease. Our aim was to describe the genetic profile of a
consecutive series of ALS patients of Sardinian ancestry. All ALS patients of
Sardinian ancestry, identified between 2008 and 2013 through the Italian ALS
Genetic Consortium, were eligible to be included in the study. Patients and
controls underwent the analysis of TARDBP, C9ORF72, SOD1, and FUS genes. Genetic
mutations were identified in 155 out of 375 Sardinian ALS cases (41.3%), more
commonly the p.A382T and p.G295S mutations of TARDBP and the GGGGCC
hexanucleotide repeat expansion of C9ORF72. One patient had both p.G295S and
p.A382T mutations of TARDBP and 8 carried both the heterozygous p.A382T mutation
of TARDBP and a repeat expansion of C9ORF72. Patients carrying the p.A382T and
the p.G295S mutations of TARDBP and the C9ORF72 repeat expansion shared distinct
haplotypes across these loci. Patients with cooccurrence of C9ORF72 and TARDBP
p.A382T missense mutation had a significantly lower age at onset and shorter
survival. More than 40% of all cases on the island of Sardinia carry a mutation
of an ALS-related gene, representing the highest percentage of ALS cases
genetically explained outside of Scandinavia. Clinical phenotypes associated with
different genetic mutations show some distinctive characteristics, but the
heterogeneity between and among families carrying the same mutations implies that
ALS manifestation is influenced by other genetic and nongenetic factors.
PMID- 25123921
TI - Cell responses to metallic nanostructure arrays with complex geometries.
AB - Metallic nanopillar/nanowires are emerging as promising platforms for biological
applications, as they allow for the direct characterization and regulation of
cell function. Herein we study the response of cells to a versatile nanopillar
platform. Nanopillar arrays of various shape, size, and spacing and different
nanopillar-substrate interfacial strengths were fabricated and interfaced with
fibroblasts and several unique cell-nanopillar interactions were observed using
high resolution scanning electron microscopy. Nanopillar penetration, engulfment,
tilting, lift off and membrane thinning, were observed by manipulating nanopillar
material, size, shape and spacing. These unique cell responses to various
nanostructures can be employed for a wide range of applications including the
design of highly sensitive nano-electrodes for single-cell probing.
PMID- 25123917
TI - Neurofeedback in children with attention-deficit/hyperactivity disorder (ADHD)--a
controlled multicenter study of a non-pharmacological treatment approach.
AB - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is the most common
neurobehavioral disorder of childhood and has often a chronic course persisting
into adulthood. However, up to 30% of children treated with stimulants either
fail to show an improvement or suffer adverse side effects, including decreased
appetite, insomnia and irritability and there is no evidence of long term
efficacy of stimulants for ADHD. A series of studies has shown that neurofeedback
is an effective additional or alternative treatment for children with ADHD,
leading to e.g. significant and stable improvement in behavior, attention and IQ.
Significant treatment effects of neurofeedback have also been verified in meta
analyses. Most of the trials, however, have been criticized for methodological
difficulties, particularly lacking appropriate control conditions and number of
patients included. This randomized study examines the efficacy of slow cortical
potentials (SCP) -neurofeedback, controlling unspecific effects of the setting by
comparing two active treatment modalities. METHODS/DESIGN: A total of 144
patients with ADHD, older than six and younger than ten years, in some cases with
additional pharmacological treatment, are included in this trial. In five trial
centres patients are treated either with SCP-feedback or electromyographic (EMG)
feedback in 25 sessions within 3 months. A comprehensive test battery is
conducted before and after treatment and at follow-up 6 month later, to assess
core symptoms of ADHD, general psychopathology, attentional performance, comorbid
symptoms, intelligence, quality of life and cortical arousal. DISCUSSION: The
efficacy of SCP-feedback training for children with ADHD is evaluated in this
randomized controlled study. In addition to behavior ratings and psychometric
tests neurophysiological parameters serve as dependent variables. Further, the
choice of EMG-biofeedback as an active control condition is debated. TRIALS
REGISTRATION: Current Controlled Trials ISRCTN76187185. Registered 5 February
2009.
PMID- 25123922
TI - Surface chemistry dependent immunostimulative potential of porous silicon
nanoplatforms.
AB - Nanoparticles (NPs) have been suggested for immunotherapy applications in order
to optimize the delivery of immuno-stimulative or -suppressive molecules.
However, low attention towards the impact of the NPs' physicochemical properties
has presented a major hurdle for developing efficient immunotherapeutic agents.
Here, the effects of porous silicon (PSi) NPs with different surface chemistries
were evaluated on human monocyte-derived dendritic cells (MDDCs) and lymphocytes
in order to highlight the importance of the NPs selection in immuno-stimulative
or -suppressive treatment. Although all the PSi NPs showed high biocompatibility,
only thermally oxidized PSi (TOPSi) and thermally hydrocarbonized PSi (THCPSi)
NPs were able to induce very high rate of immunoactivation by enhancing the
expression of surface co-stimulatory markers of the MDDCs (CD80, CD83, CD86, and
HLA-DR), inducing T-cell proliferation, and also the secretion of interleukins
(IL-1beta, IL-4, IL-6, IL-10, IL-12, IFN-gamma, and TNF-alpha). These results
indicated a balanced increase in the secretion of Th1, Th2, and Treg cytokines.
Moreover, undecylenic acid functionalized THCPSi, as well as poly(methyl vinyl
ether-alt-maleic acid) conjugated to (3-aminopropyl)triethoxysilane
functionalized thermally carbonized PSi and polyethyleneimine conjugated
undecylenic acid functionalized THCPSi NPs showed moderate immunoactivation due
to the mild increase in the above-mentioned markers. By contrast, thermally
carbonized PSi (TCPSi) and (3-aminopropyl)triethoxysilane functionalized TCPSi
NPs did not induce any immunological responses, suggesting that their application
could be in the delivery of immunosuppressive molecules. Overall, our findings
suggest all the NPs containing more nitrogen or oxygen on the outermost backbone
layer have lower immunostimulatory effect than NPs with higher C-H structures on
the surface.
PMID- 25123923
TI - The osteogenic differentiation of SSEA-4 sub-population of human adipose derived
stem cells using silicate nanoplatelets.
AB - How to surpass in vitro stem cell differentiation, reducing cell manipulation,
and lead the in situ regeneration process after transplantation, remains to be
unraveled in bone tissue engineering (bTE). Recently, we showed that the
combination of human bone marrow stromal cells with bioactive silicate
nanoplatelets (sNPs) promotes the osteogenic differentiation without the use of
standard osteogenic inductors. Even more, using SSEA-4(+) cell-subpopulations
(SSEA-4(+)hASCs) residing within the adipose tissue, as a single-cellular source
to obtain relevant cell types for bone regeneration, was also proposed. Herein,
sNPs were used to promote the osteogenic differentiation of SSEA-4(+)hASCs. The
interactions between SSEA-4(+)hASCs and sNPs, namely the internalization pathway
and effect on cells osteogenic differentiation, were evaluated. SNPs below 100
MUg/mL showed high cytocompatibility and fast internalization via clathrin
mediated pathway. SNPs triggered an overexpression of osteogenic-related markers
(RUNX2, osteopontin, osteocalcin) accompanied by increased alkaline phosphatase
activity and deposition of a predominantly collagen-type I matrix. Consequently,
a robust matrix mineralization was achieved, covering >90% of the culturing
surface area. Overall, we demonstrated the high osteogenic differentiation
potential of SSEA-4(+)hASCs, further enhanced by the addition of sNPs in a dose
dependent manner. This strategy endorses the combination of an adipose-derived
cell-subpopulation with inorganic compounds to achieve bone matrix-analogs with
clinical relevance.
PMID- 25123924
TI - Multiscale patterned transplantable stem cell patches for bone tissue
regeneration.
AB - Stem cell-based therapy has been proposed as an enabling alternative not only for
the treatment of diseases but also for the regeneration of tissues beyond complex
surgical treatments or tissue transplantation. In this study, we approached a
conceptual platform that can integrate stem cells into a multiscale patterned
substrate for bone regeneration. Inspired by human bone tissue, we developed
hierarchically micro- and nanopatterned transplantable patches as synthetic
extracellular matrices by employing capillary force lithography in combination
with a surface micro-wrinkling method using a poly(lactic-co-glycolic acid)
(PLGA) polymer. The multiscale patterned PLGA patches were highly flexible and
showed higher tissue adhesion to the underlying tissue than did the single
nanopatterned patches. In response to the anisotropically multiscale patterned
topography, the adhesion and differentiation of human mesenchymal stem cells
(hMSCs) were sensitively controlled. Furthermore, the stem cell patch composed of
hMSCs and transplantable PLGA substrate promoted bone regeneration in vivo when
both the micro- and nanotopography of the substrate surfaces were synergistically
combined. Thus, our study concludes that multiscale patterned transplantable stem
cell patches may have a great potential for bone regeneration as well as for
various regenerative medicine approaches.
PMID- 25123925
TI - Effective ovarian stimulation in a patient with resistant ovary syndrome and
antigonadotrophin antibodies.
AB - PROBLEM: We report on a successful ovarian stimulation and pregnancy in a patient
with 'resistant ovary syndrome' (ROS) and antigonadotrophin antibodies. ROS is
characterized by high endogenous gonadotrophins, low estradiol, normal ovarian
antral follicle counts and normal antimuellerian hormone values. METHOD OF STUDY:
After cyclical hormone treatment, downregulation with GnRH analogue and ICSI
procedure followed. Granulosa cells were treated with LH, FSH or hMG and
expression of receptors for FSH, LH, oestrogen receptor beta (ERb) and
progesterone receptor A (PR-A) was determined. Serum of the patient was analysed
for antibodies directed against hMG. RESULTS: After fertilization of ten
metaphase II oocytes and transfer of two blastocysts, a singleton pregnancy was
established. Stimulation of granulosa cells with FSH, LH and hMG upregulated ERb
and PR-A. Dot blot analysis showed strong reactivity with hMG but not with
recFSH. CONCLUSION: This patient with normal expression of gonadotrophin
receptors showed antibodies directed to hMG but not to recFSH.
PMID- 25123926
TI - Cerebellar abnormalities in Huntington's disease: a role in motor and psychiatric
impairment?
AB - The cerebellum has received limited attention in Huntington's disease (HD),
despite signs of possible cerebellar dysfunction, including motor incoordination
and impaired gait, which are currently attributed to basal ganglia atrophy and
disrupted fronto-striatal circuits. This study is the first to investigate a
potential contribution of macro- and microstructural cerebellar damage to
clinical manifestations of HD. T1- and diffusion-weighted 3T magnetic resonance
imaging (MRI) scans were obtained from 12 controls and 22 early-stage HD
participants. Manual delineation and voxel-based morphometry were used to assess
between-group differences in cerebellar volume, and diffusion metrics were
compared between groups within the cerebellar gray and white matter. Associations
between these imaging measures and clinical scores were examined within the HD
group. Reduced paravermal volume was detected in HD compared with controls using
voxel-based morphometry (P < 0.05), but no significant volumetric differences
were found using manual delineation. Diffusion abnormalities were detected in
both cerebellar gray matter and white matter. Smaller cerebellar volumes,
although not significantly reduced, were significantly associated with impaired
gait and psychiatric morbidity and of borderline significance with
pronate/supinate-hand task performance. Abnormal cerebellar diffusion was
associated with increased total motor score, impaired saccade initiation, tandem
walking, and timed finger tapping. In conclusion, atrophy of the paravermis,
possibly encompassing the cerebellar nuclei, and microstructural abnormalities
within the cerebellum may contribute to HD neuropathology. Aberrant cerebellar
diffusion and reduced cerebellar volume together associate with impaired motor
function and increased psychiatric symptoms in stage I HD, potentially
implicating the cerebellum more centrally in HD presentation than previously
recognized.
PMID- 25123927
TI - [Nostalgia and the functions of autobiographical memory].
AB - BACKGROUND: Current research on autobiographical memory distinguishes between a
self function, a directive function, and a social function of autobiographical
memory. From a lifespan perspective, the use of autobiographical memory for these
functions is expected to decrease with age. The present study extended these
functions by the function of nostalgia: Often triggered by negative emotions,
remembering personal and positive experiences might, among others, enhance
positive effects. This emotion-regulating function is expected to become more
important in old age. MATERIAL AND METHODS: In the present study 273 adults (aged
between 19 and 90 years) completed the Thinking About Life Experiences
Questionnaire (TALE) as well as 11 newly developed items to assess the nostalgia
function. RESULTS: Exploratory and confirmatory factor analyses supported a four
factor model reflecting the presumed self, directive, social, and nostalgia
functions of autobiographical memory. The results showed a decrease in the use of
autobiographical memory for self, directive and social functions with increasing
age, whereas the nostalgia function followed a U-shaped pattern.
PMID- 25123928
TI - Geographic and racial-ethnic differences in satisfaction with and perceived
benefits of mental health services.
AB - OBJECTIVE: This study examined whether racial-ethnic differences in satisfaction
with and perceived benefits from mental health services vary by geographic region
among U.S. adults. METHODS: Drawn from the Collaborative Psychiatric Epidemiology
Surveys (CPES), selected samples consisted of 2,160 adults age 18 and older from
diverse racial-ethnic groups (Asian, black, Hispanic/Latino, and white) who had
used mental health services in the past 12 months. Generalized linear model
analysis was conducted for the United States as a whole and separately by
geographic region (Northeast, South, Midwest, and West) after adjustment for
covariates. RESULTS: In the national sample, no significant main effects of race
ethnicity and geographic region were found in either satisfaction with or
perceived benefits from mental health services. In the stratified analyses for
geographic regions, however, significant racial-ethnic differences were observed
in the West; blacks in the West were significantly more likely to report higher
satisfaction and perceived benefits, whereas Hispanics/Latinos in the West were
significantly less likely to do so. CONCLUSIONS: The findings suggest that there
are regional variations of racial-ethnic differences in satisfaction with and
perceived benefits from mental health services among U.S. adults and that
addressing needs of Hispanics/Latinos in the West may help reduce racial-ethnic
disparities in mental health care. Clinical and policy implications are
discussed.
PMID- 25123929
TI - Mitotic DNA damages induced by carbon-ion radiation incur additional chromosomal
breaks in polyploidy.
AB - Compared with low linear energy transfer (LET) radiation, carbon-ion radiation
has been proved to induce high frequency of more complex DNA damages, including
DNA double strands (DSBs) and non-DSB clustered DNA lesions. Chemotherapeutic
drug doxorubicin has been reported to elicit additional H2AX phosphorylation in
polyploidy. Here, we investigated whether mitotic DNA damage induced by high-LET
carbon-ion radiation could play the same role. We demonstrate that impairment of
post-mitotic G1 and S arrest and abrogation of post-mitotic G2-M checkpoint
failed to prevent mis-replication of damaged DNA and mis-separation of
chromosomes. Meanwhile, mitotic slippage only nocodazole-related, cytokinesis
failure and cell fusion collectively contributed to the formation of binucleated
cells. Chk1 and Cdh1 activation was inhibited when polyploidy emerged in force,
both of which are critical components for mitotic exit and cytokinesis. Carbon
ion radiation irrelevant of nocodazole incurred additional DNA breaks in
polyploidy, manifesting as structural and numerical karyotype changes. The
proliferation of cells given pre-synchronization and radiation was completely
inhibited and cells were intensely apoptotic. Since increased chromosomal damage
resulted in extensive H2AX phosphorylation during polyploidy, we propose that the
additional gamma-H2AX during polyploidy incurred by carbon-ion radiation provides
a final opportunity for these dangerous and chromosomally unstable cells to be
eliminated.
PMID- 25123930
TI - Molecular differentiation of Central European blowfly species (Diptera,
Calliphoridae) using mitochondrial and nuclear genetic markers.
AB - A challenging step in medical, veterinary and forensic entomology casework is the
rapid and accurate identification of insects to estimate the period of insect
activity (PIA), which usually approximates the post-mortem interval (PMI). The
morphological identification of insect evidence is hampered by species
similarities, especially at the early larval stages. However, DNA-based species
identification is more accurate and reliable. In this study, we improved the
suitability and efficacy of the standard mitochondrial cytochrome c oxidase
subunit I (COI) barcode region of 658 bp combined with an additional region of
616 bp of the same gene. We also tested the usefulness of other mitochondrial and
nuclear loci, such as the non-coding region included in mitochondrial Cyt-b
tRNA(ser)-ND1 (495-496 bp) and the second internal transcribed spacer (ITS2)
region of nuclear ribosomal DNA (rDNA) (310-337 bp). We classified a total of 54
specimens from five blowfly species belonging to three Calliphoridae genera
commonly found in Central Europe: Phormia (P. regina), Calliphora (C. vicina) and
Lucilia (L. sericata, L. ampullacea and L. caesar). Additionally included were
the Cyt-b (307 bp) sequences for P. regina species and GenBank recorded
information about the studied loci for select species. The results revealed the
robustness of COI (616 bp) and ITS2 (310-337 bp) as diagnostic tools to be added
to the widely established COI barcode (658 bp). Their higher discriminatory power
allows for more precise and reliable identifications, even within more complex
genera (Lucilia). This work also contributes new nucleotide sequences that are
useful for accurate species diagnosis and new sequence data of Calliphoridae
interspecific variability in the European Westphalia region (Germany).
PMID- 25123932
TI - Pyridoxine-derived organoselenium compounds with glutathione peroxidase-like and
chain-breaking antioxidant activity.
AB - One of the vitamin B6 vitamers, pyridoxine, was modified to incorporate selenium
in various oxidation states in place of the methyl group in position 2. Such
compounds were conveniently accessed by treatment of bis-4,5-(carboethoxy)-2-iodo
3-pyridinol with disodium diselenide and LiAlH4 -reduction. After work-up, selone
7 was isolated in good yield as an air-stable crystalline material. Hydrogen
bonding to the neighboring hydroxyl group, as revealed by the short
intramolecular Se???H distance in the crystal structure is likely to provide
extra stabilization to the compound. Computational studies showed that selone 7
is more stable than the corresponding selenol tautomer by 12.2 kcal mol(-1) .
Hydrogen peroxide oxidation of the selone 7 afforded diselenide 12, and, on
further oxidation, seleninic acid 13. Treatment of the seleninic acid with
thiophenol provided an isolable selenosulfide 14. The glutathione peroxidase-like
properties of the pyridoxine-derived compounds were assessed by using the coupled
reductase method. Seleninic acid 13 was found to be twofold more active than
ebselen. The chain-breaking capacity of the pyridoxine compounds were studied in
a water/chlorobenzene membrane model containing linoleic acid as an oxidizable
substrate and N-acetylcysteine as a thiol reducing agent. Diselenide 15 could
match alpha-tocopherol when it comes to reactivity towards peroxyl radicals and
inhibition time.
PMID- 25123933
TI - The Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) survey: provider
practices and beliefs about allergen immunotherapy.
AB - BACKGROUND: The practices and beliefs of the provider specialties that treat
allergic rhinoconjunctivitis (ARC) with allergen immunotherapy (AIT) may vary.
METHODS: A telephone survey of 500 randomly selected health care practitioners in
7 specialties, conducted in 2012. RESULTS: AIT was provided as a subcutaneous
injection (SCIT) by 91% of allergist/immunologists, 54% of otolaryngologists, and
18% to 24% of other specialties. Otolaryngologists were the most frequent
providers of sublingual drops of AIT (SLIT; 33%), compared to 2% to 10% of other
specialties. AIT was recommended for adults with allergic rhinoconjunctivitis by
100% of allergist/immunologists vs 62% to 84% of the other specialties (p <
0.001). The primary reason for recommending AIT for adults (52%) or children
(46%) was that other therapies did not work. Between 48% (nurse
practitioners/physician assistants) and 93% (allergist/immunologists) of
practitioners always or often decreased symptomatic medications over the course
of AIT treatment. Most practitioners in all specialties (82-100%) thought that
AIT was appropriate for patients with severe allergy symptoms. Significantly more
allergist/immunologists and otolaryngologists than other specialists thought AIT
was appropriate for mild allergy symptoms (p < 0.001 and p = 0.004, respectively,
vs other specialties). Significantly more allergist/immunologists than other
specialists thought that AIT was more effective than symptomatic medications (p <
0.001), could reduce the further development of allergies (p = 0.03), and could
prevent the development of asthma. CONCLUSION: SCIT was more frequently provided
than SLIT by all the specialties. Otolaryngologists were the most likely to offer
SLIT, while very few allergist/immunologists offered SLIT.
Allergist/immunologists differed from other specialties in some beliefs about the
effectiveness of AIT.
PMID- 25123931
TI - Helicobacter pylori targets cancer-associated apical-junctional constituents in
gastroids and gastric epithelial cells.
AB - OBJECTIVE: Helicobacter pylori strains that express the oncoprotein CagA augment
risk for gastric cancer. However, the precise mechanisms through which cag(+)
strains heighten cancer risk have not been fully delineated and model systems
that recapitulate the gastric niche are critical for understanding pathogenesis.
Gastroids are three-dimensional organ-like structures that provide unique
opportunities to study host-H. pylori interactions in a preclinical model. We
used gastroids to inform and direct in vitro studies to define mechanisms through
which H. pylori modulates expression of the cancer-associated tight junction
protein claudin-7. DESIGN: Gastroids were infected by luminal microinjection, and
MKN28 gastric epithelial cells were cocultured with H. pylori wild-type cag(+)
strains or isogenic mutants. beta-catenin, claudin-7 and snail localisation was
determined by immunocytochemistry. Proliferation was assessed using 5-ethynyl-2'
deoxyuridine, and levels of claudin-7 and snail were determined by western blot
and flow cytometry. RESULTS: Gastroids developed into a self-organising
differentiation axis and H. pylori induced mislocalisation of claudin-7 and
increased proliferation in a CagA- and beta-catenin-dependent manner. In MKN28
cells, H pylori-induced suppression of claudin-7 was regulated by beta-catenin
and snail. Similarly, snail expression was increased and claudin-7 levels were
decreased among H. pylori-infected individuals. CONCLUSIONS: H. pylori increase
proliferation in a strain-specific manner in a novel gastroid system. H. pylori
also alter expression and localisation of claudin-7 in gastroids and human
epithelial cells, which is mediated by beta-catenin and snail activation. These
data provide new insights into molecular interactions with carcinogenic potential
that occur between H. pylori and epithelial cells within the gastric niche.
PMID- 25123934
TI - Towards elucidating the stability, dynamics and architecture of the nucleosome
remodeling and deacetylase complex by using quantitative interaction proteomics.
AB - The nucleosome remodeling and deacetylase (NuRD) complex is an evolutionarily
conserved chromatin-associated protein complex. Although the subunit composition
of the mammalian complex is fairly well characterized, less is known about the
stability and dynamics of these interactions. Furthermore, detailed information
regarding protein-protein interaction surfaces within the complex is still
largely lacking. Here, we show that the NuRD complex interacts with a number of
substoichiometric zinc finger-containing proteins. Some of these interactions are
salt-sensitive (ZNF512B and SALL4), whereas others (ZMYND8) are not. The
stoichiometry of the core subunits is not affected by high salt concentrations,
indicating that the core complex is stabilized by hydrophobic interactions.
Interestingly, the RBBP4 and RBBP7 proteins are sensitive to high nonionic
detergent concentrations during affinity purification. In a subunit exchange
assay with stable isotope labeling by amino acids in cell culture (SILAC)-treated
nuclear extracts, RBBP4 and RBBP7 were identified as dynamic core subunits of the
NuRD complex, consistent with their proposed role as histone chaperones. Finally,
using cross-linking MS, we have uncovered novel features of NuRD molecular
architecture that complement our affinity purification-MS/MS data. Altogether,
these findings extend our understanding of MBD3-NuRD structure and stability.
STRUCTURED DIGITAL ABSTRACT: MBD3 physically interacts with ZNF512B, HDAC1,
ZMYND8, GATAD2B, SALL4, GATAD2A, ZNF592, MTA3, ZNF687, CDK2AP1, CHD3, ZNF532,
HDAC2, MTA2, CHD4, MTA1, KPNA2, CHD5, RBBP4 and RBBP7 by pull down (View
interaction) CDK2AP1 physically interacts with MBD3, MTA3, HDAC2, GATAD2A, CHD4,
CDK2AP1, MTA2, HDAC1, MTA1, CHD3, GATAD2B, MBD2, RBBP4 and RBBP7 by pull down
(View interaction) MBD3 physically interacts with MTA2, MTA3, RBBP4, RBBP7,
HDAC2, HDAC1, CHD4, CHD3 and MTA1 by cross-linking study (View interaction).
PMID- 25123936
TI - Detection of cyanobacterial neurotoxin beta-N-methylamino-l-alanine within
shellfish in the diet of an ALS patient in Florida.
AB - Cyanobacteria produce the neurotoxic amino acid beta-N-methylamino-l-alanine
(BMAA), which in contaminated marine waters has been found to accumulate in
shellfish. Exposure to BMAA has been associated with an increased risk of
neurodegenerative disease. Analysis of blinded samples found BMAA to be present
in neuroproteins of individuals who died from ALS and ALS/PDC, but generally not
in the brains of patients who died of causes unrelated to neurodegeneration or
Huntington's disease, an autosomal dominant neurodegenerative disease. We here
report support for a link between a patient with ALS and chronic exposure to the
cyanobacterial neurotoxin BMAA via shellfish consumption. The patient had
frequently eaten lobsters collected in Florida Bay for approximately 30 years. LC
MS/MS analysis of two lobsters which this ALS patient had placed in his freezer
revealed BMAA at concentrations of 27 and 4 MUg/g, respectively, as well as the
presence of 2,4-diaminobutyric acid (DAB), a BMAA isomer. Two additional lobsters
recently collected from Florida Bay also contained the neurotoxins BMAA and DAB.
These data suggest that invertebrates collected in water where cyanobacterial
blooms are present, if consumed, may result in direct human exposure to these
neurotoxic amino acids. The data support the assertion that prolonged exposure to
BMAA may have played a role in the etiology of ALS in this patient.
PMID- 25123935
TI - The necrotrophic effector protein SnTox3 re-programs metabolism and elicits a
strong defence response in susceptible wheat leaves.
AB - BACKGROUND: The fungus Stagonospora nodorum is a necrotrophic pathogen of wheat.
It causes disease by secreting proteinaceous effectors which interact with
proteins encoded by dominant susceptibility genes in the host. The outcome of
these interactions results in necrosis, allowing the fungus to thrive on dead
plant material. The mechanisms of these effectors though are poorly understood.
In this study, we undertake a comprehensive transcriptomics, proteomic and
metabolomic approach to understand how a susceptible wheat cultivar responds to
exposure to the Stagonospora nodorum effector protein SnTox3. RESULTS: Microarray
and proteomic studies revealed that SnTox3 strongly induced responses consistent
with those previously associated with classical host defence pathways including
the expression of pathogenicity-related proteins and the induction of cell death.
Collapse of the photosynthetic machinery was also apparent at the transcriptional
and translational level. SnTox3-infiltrated wheat leaves also showed a strong
induction of enzymes involved in primary metabolism consistent with increases in
hexoses, amino acids and organic acids as determined by primary metabolite
profiling. Methionine and homocysteine metabolism was strongly induced upon
exposure to SnTox3. Pathogenicity in the presence of homocysteine was inhibited
confirming that the compound has a role in plant defence. Consistent with the
strong defence responses observed, secondary metabolite profiling revealed the
induction of several compounds associated with plant defence, including the
phenylpropanoids chlorogenic acid and feruloylquinic acid, and the cyanogenic
glucoside dhurrin. Serotonin did not accumulate subsequent to SnTox3
infiltration. CONCLUSIONS: These data support the theory that the SnTox3 effector
protein elicits a host cell death response to facilitate the pathogen's
necrotrophic infection cycle. Our data also demonstrate that the mechanism of
SnTox3 appears distinct from the previously characterised Stagonospora nodorum
effector SnToxA. Collectively, this comprehensive analysis has advanced our
understanding of necrotrophic effector biology and highlighted the complexity of
effector-triggered susceptibility.
PMID- 25123937
TI - Complex formation of Sn(II) with glycine: an IR, DTA/TGA and DFT investigation.
AB - The novel Sn(Gly)2?H2O complex compound has been synthesized and characterized by
TGA, IR and Raman spectroscopy. Molecular spectroscopy and ab initio simulation
have given the evidence of glycine molecule being coordinated to Sn(II) as
bidentate chelating ligand by oxygen atom of carboxyl group and nitrogen atom of
amino group. Water molecule is bonded with amino and carboxylic groups by
hydrogen bonds in the out sphere. The M06, TPSS, TPSSm, TPSSh and revTPSS density
functionals have been tested for calculation of structural and vibrational data.
The vibrational assignment of experimental IR and Raman and simulated spectra has
been carried out. The TPSS and TPSSm density functionals and Def2-TZVP basis set
have provided the most accurate results.
PMID- 25123938
TI - Charge-transfer complexes of 4-methylpiperidine with sigma- and pi-acceptors.
AB - The solid charge-transfer (CT) molecular complexes formed in the reaction of the
electron donor 4-methylpiperidine (4MP) with the sigma-electron acceptor iodine
and pi-acceptors 7,7,8,8-tetracyanoquinodimethane (TCNQ), 2,3-dichloro-5,6
dicyano-1,4-benzoquinone (DDQ) and 2,4,4,6-tetrabromo-2,5-cyclohexadienone
(TBCHD) have been investigated spectrophotometrically in chloroform at 25
degrees C. These were characterized through electronic and infrared spectra as
well as elemental and thermal analysis. The obtained results showed that the
formed solid CT-complexes have the formulas [(4MP) I](+)I(-)3, [(4MP)(DDQ)2] and
[(4MP)(TBCHD)] and with TCNQ the adduct [TCMPQDM] is obtained through N
substitution reaction in full agreement with the known reaction stoichiometries
in solution as well as the elemental measurements. The formation constant KCT,
molar extinction coefficient epsilonCT, free energy change DeltaG(0), CT energy
ECT and the ionization potential Ip have been calculated for the CT-complexes
[(4MP) I](+)I(-)3, [(4MP)(DDQ)2] and [(4MP)(TBCHD)].
PMID- 25123939
TI - Determination of trace amount of formaldehyde base on a bromate-Malachite Green
system.
AB - A novel catalytic kinetic spectrophotometric method for determination of trace
amount of formaldehyde (FA) has been established, based on catalytic effect of
trace amount of FA on the oxidation of Malachite Green (MG) by potassium bromate
in presence of sulfuric acid medium, and was reported for the first time. The
method was monitored by measuring the decrease in absorbance of MG at 617 nm and
allowed a precise determination of FA in the range of 0.003-0.08 MUg mL(-1), with
a limit of detection down to 1 ng mL(-1). The relative standard deviation of 10
replicate measurements was 1.63%. The method developed was approved to be
sensitive, selective and accurate, and adopted to determinate free FA in samples
directly with good accuracy and reproducibility.
PMID- 25123940
TI - Spectroscopic analyses and studies on respective interaction of cyanuric acid and
uric acid with bovine serum albumin and melamine.
AB - In this work, the fluorescence quenching was used to study the interaction of
cyanuric acid (CYA) and uric acid (UA) with bovine serum albumin (BSA) at two
different temperatures (283 K and 310 K). The bimolecular quenching constant
(Kq), apparent quenching constant (Ksv), effective binding constant (KA) and
corresponding dissociation constant (KD), binding site number (n) and binding
distance (r) were calculated by adopting Stern-Volmer, Lineweaver-Burk, Double
logarithm and overlap integral equations. The results show that CYA and UA are
both able to obviously bind to BSA, but the binding strength order is
BSA+CYA3 months) in patients having external mesh support as part of CABG. METHODS:
From October 25, 2010 through February 13, 2012, 21 patients had external mesh
support of SVG grafts in addition to internal thoracic artery grafting to the
Anterior Descending artery. Patients were invited to return for patency
evaluation using Computerized Tomographic angiography (CTA) an average of 7.2
months post-operative (R = 3-14 months). RESULTS: 21 male patients (age 57+/- 9
years) underwent on-pump surgery. The eSVS Mesh was successfully placed on all
SVGs. All grafts were determined patent intra-operative by transit time Doppler
measurement and there were no operative revisions. There was no operative
mortality. 12 of the 21 contacted patients returned for CTA, 8 non-returning
patients contacted were alive and asymptomatic but refused to return due to
travel restrictions or cost. One patient was lost to follow up. 11 returning
patients underwent CTA. One patient was excluded (asymptomatic) due to elevated
creatinine. Of the 23 anastomoses in 11 patients(Average: 2.09 grafts/patient)
using SVG available for examination, 21 were patent (92%). CONCLUSIONS: In this
retrospective non-randomized experience, the external mesh supported grafts
displayed excellent intermediate patency.
PMID- 25123949
TI - Role of BRAF molecular analysis in the management of papillary thyroid carcinoma:
analysis of cytological and histological samples.
AB - BACKGROUND: Although fine needle aspiration (FNA) is the standard diagnostic test
for the characterization of a suspicious thyroid nodule, in some cases
cytological evaluation is inconclusive. The aim of this study was to determine
the role of BRAF mutation in aiding diagnosis and to verify whether archival
cytological samples could be suitable for molecular analysis. METHODS: Eighty
five patients with suspicious (Thy4) or follicular (Thy3) lesions on cytology
were resubmitted to a second FNA for BRAF mutation analysis. Of these, 56
subsequently underwent surgery. The usefulness of archival samples for molecular
analysis was also studied in a second cohort of 42 patients with a confirmed
diagnosis of papillary thyroid carcinoma for whom both archived paraffin-embedded
histological samples and cytological smears were available. A further 15 patients
with paired fresh FNA and archived cytological and histological samples were
recruited. RESULTS: BRAF mutation was found in the fresh FNA samples from 10 of
56 patients who had surgery with previous inconclusive cytology (4/45, 9%, Thy3
and 6/11, 55%, Thy4). The BRAF test showed a specificity and positive predictive
value of 100% (26/26 and 10/10, respectively), sensitivity of 33% (10/30) and
negative predictive value of 57% (26/46). There was absolute concordance between
the BRAF results obtained with 42 histological and cytological archived samples.
BRAF analysis on 15 archived cytological samples showed absolute concordance with
histology, whereas there was one false negative on the matched fresh FNA.
CONCLUSION: BRAF analysis is a highly specific test that can facilitate
cytological diagnosis in some cases and can also be performed on archived
cytological samples.
PMID- 25123950
TI - Level of adherence to the GOLD strategy document for management of patients
admitted to hospital with an acute exacerbation of COPD.
AB - BACKGROUND AND OBJECTIVE: The Global initiative for chronic Obstructive Lung
Disease (GOLD) strategy document has been available since 2001. Little is known
about level of adherence to the GOLD document among hospital-based health
professionals assessing and managing inpatients admitted with an acute
exacerbation of chronic obstructive pulmonary disease (AECOPD). The primary aim
of the study was to evaluate the level of adherence among health professionals to
GOLD. METHODS: A retrospective audit of medical histories was completed on a
random sample of 240 patients admitted to hospital with a primary diagnosis of
AECOPD within a calendar year. The audit evaluated adherence to GOLD
recommendations on appropriateness of hospital and intensive care unit admissions
as well as pharmacological and non-pharmacological management. RESULTS: High
levels of adherence to indications for hospital admissions (97%), indications for
intensive care unit admissions (100%) and prescription of bronchodilators (100%)
were observed. However, antibiotics (45%) and oxygen therapy (68%) were over
prescribed. Adherence to non-pharmacological management was poor in areas such as
smoking cessation (25%) and pulmonary rehabilitation referrals (16%). Patients
admitted under the care of the respiratory team were more likely (odds ratio =
2.6, 95% confidence interval: 1.3-5.4) to be referred to pulmonary rehabilitation
than patients admitted under the general medicine team. CONCLUSIONS: Health
professionals in the respiratory team had better adherence to GOLD as compared to
health professionals in other teams. Nonetheless, pharmacological interventions
were both appropriately prescribed and also over-prescribed, whereas non
pharmacological interventions were used rarely, suggesting a need for practice
review in these areas.
PMID- 25123951
TI - Optimizing Rubisco and its regulation for greater resource use efficiency.
AB - Rubisco catalyses the carboxylation of ribulose-1,5-bisphosphate (RuBP), enabling
net CO2 assimilation in photosynthesis. The properties and regulation of Rubisco
are not optimal for biomass production in current and projected future
environments. Rubisco is relatively inefficient, and large amounts of the enzyme
are needed to support photosynthesis, requiring large investments in nitrogen.
The competing oxygenation of RuBP by Rubisco decreases photosynthetic efficiency.
Additionally, Rubisco is inhibited by some sugar phosphates and depends upon
interaction with Rubisco activase (Rca) to be reactivated. Rca activity is
modulated by the chloroplast redox status and ADP/ATP ratios, thereby mediating
Rubisco activation and photosynthetic induction in response to irradiance. The
extreme thermal sensitivity of Rca compromises net CO2 assimilation at moderately
high temperatures. Given its central role in carbon assimilation, the improvement
of Rubisco function and regulation is tightly linked with irradiance, nitrogen
and water use efficiencies. Although past attempts have had limited success,
novel technologies and an expanding knowledge base make the challenge of
improving Rubisco activity in crops an achievable goal. Strategies to optimize
Rubisco and its regulation are addressed in relation to their potential to
improve crop resource use efficiency and climate resilience of photosynthesis.
PMID- 25123952
TI - Massive open online courses on health and medicine: review.
AB - BACKGROUND: Massive open online courses (MOOCs) have become immensely popular in
a short span of time. However, there is very little research exploring MOOCs in
the discipline of health and medicine. OBJECTIVE: We aim to provide a review of
MOOCs related to health and medicine offered by various MOOC platforms in 2013,
by analyzing and comparing the various offerings, their target audience, typical
length of course, and credentials offered. We also discuss opportunities and
challenges presented by MOOCs in health and medicine. METHODS: Health and
medicine-related MOOCs were gathered using several methods to ensure the richness
and completeness of data. Identified MOOC platform websites were used to gather
the lists of offerings. In parallel, these MOOC platforms were contacted to
access official data on their offerings. Two MOOC aggregator sites (Class Central
and MOOC List) were also consulted to gather data on MOOC offerings. Eligibility
criteria were defined to concentrate on the courses that were offered in 2013 and
primarily on the subject of health and medicine. All language translations in
this paper were done using Google Translate. RESULTS: The search identified 225
courses, of which 98 were eligible for the review. Over half (58%, 57/98) of the
MOOCs considered were offered on the Coursera platform, and 94% (92/98) of all
the MOOCs were offered in English. Universities offered 90 MOOCs, and the John
Hopkins University offered the largest number of MOOCs (12/90). Only three MOOCs
were offered by developing countries (China, West Indies, and Saudi Arabia). The
duration of MOOCs varied from 3-20 weeks with an average length of 6.7 weeks. On
average, MOOCs expected a participant to work on the material for 4.2 hours a
week. Verified certificates were offered by 14 MOOCs, while three others offered
other professional recognition. CONCLUSIONS: The review presents evidence to
suggest that MOOCs can be used as a way to provide continuous medical education.
It also shows the potential of MOOCs as a means of increasing health literacy
among the public.
PMID- 25123954
TI - Current management of papillary thyroid microcarcinoma in Canada.
AB - INTRODUCTION: The detection of papillary thyroid microcarcinoma (PTMC) is on the
rise and its optimal management remains controversial. Our aim was to determine
the current self-reported management of PTMC amongst Canadian otolaryngologist
head and neck surgeons (OHNS) and endocrinologists and to identify factors
influencing their management decisions. METHODS: A nine item web-based
questionnaire was distributed to Canadian OHNS and endocrinologists. The three
main domains were demographics, current management of PTMC scenarios, and factors
influencing the decisions. RESULTS: One hundred and thirteen OHNS and
endocrinologists completed the survey. Respondents were closely divided between
recommending hemithyroidectomy (47%) or total thyroidectomy (43%) for a newly
diagnosed PTMC in a low risk patient. Observation was the preferred method for
managing PTMC detected incidentally after hemithyroidectomy (76%). Respondents
chose more aggressive treatment for male patients compared to female patients. A
positive history of thyroid cancer or previous radiation exposure was the most
important factor influencing the management of PTMC. CONCLUSION: The current
practices of Canadian OHNS and endocrinologist largely coincide with available
guidelines. The slight variation in practice might be explained by the opposing
evidence supporting different management options. Given the dramatic increase in
the incidence of PTMC we suggest future guidelines address the management of PTMC
independently.
PMID- 25123955
TI - The problem with generic immunosuppressants.
PMID- 25123953
TI - Co-inoculation of Glomus intraradices and Trichoderma atroviride acts as a
biostimulant to promote growth, yield and nutrient uptake of vegetable crops.
AB - BACKGROUND: The application of beneficial microorganisms at transplanting can
promote rapid transplant establishment (starter effect) for achieving early and
high yields. The aim of this study was to evaluate the biostimulant effects of
Glomus intraradices BEG72 (G) and Trichoderma atroviride MUCL 45632 (T) alone or
in combination on plant growth parameters, yield, chlorophyll index (SPAD),
chlorophyll fluorescence and mineral composition of several vegetable crops.
RESULTS: The T. atroviride strain was capable of producing siderophores and auxin
like compounds under a wide range of substrate pH conditions (5.5-8.0). The
highest shoot, root dry weight, SPAD and chlorophyll fluorescence in lettuce,
tomato and zucchini was observed in the G + T combination, followed by a single
inoculation of G or T, whereas the lowest values were recorded in the
uninoculated plants. Under greenhouse conditions, the shoot dry weight was
significantly increased by 167%, 56%, 115%, 68% and 58% in lettuce, melon,
pepper, tomato and zucchini, respectively, when supplied with both beneficial
microorganisms in comparison with the control. This increase in root and shoot
weight was associated with an increased level of nutrient uptake (e.g. P, Mg, Fe,
Zn and B). Under open field conditions, the lettuce shoot and root dry weight
increased by 61% and 57%, respectively, with biostimulant microorganism
application in field conditions. For zucchini, early and total yields were
significantly increased by 59% and 15%, respectively, when plants were inoculated
with both microorganisms. CONCLUSION: The application of the biostimulant tablet
containing both G and T can promote transplant establishment and vegetable crop
productivity in a sustainable way.
PMID- 25123956
TI - Role for biological meshes for delayed abdominal wall closure after pediatric
liver transplantation?
PMID- 25123957
TI - Elucidating the nature of transformation in the adolescent transplant patient:
time to move from knowledge to action.
PMID- 25123958
TI - Factors responsible for incomplete linkage to care after HIV diagnosis:
preliminary results from the Test and Keep in Care (TAK) project.
AB - OBJECTIVES: Linkage to care after HIV diagnosis remains underinvestigated in
Europe, yet delays in linkage to care are an important obstacle to controlling
the HIV epidemic. The Test and Keep in Care (TAK) project aims to determine the
prevalence of HIV-positive persons who are lost or late to care and factors
associated with this. METHODS: Data from community-based voluntary counselling
and testing that occurred in 2010-2011 were linked with data from HIV clinics
using unique test numbers. Persons not registered in HIV clinics were considered
lost to care (LTC). For statistical analysis, nonparametric tests were used for
comparison, and a multivariable logistic regression model was developed that
included all variables with P<0.1 from the univariable models. RESULTS: A total
of 110 persons were diagnosed as HIV-positive: 91% lived in central Poland, 5%
were female and 71% were men who have sex with men (MSM). Forty-seven (42%)
persons were LTC, seven of whom did not collect their enzyme-linked immunosorbent
assay (ELISA) test result. Of those who registered, 75% registered within 1 month
from HIV diagnosis, and 54% were late presenters. LTC individuals were more
likely to have heterosexual or bisexual orientation, to have >20 sexual partners,
to not be in a relationship with an HIV-positive partner, to not use condoms, and
to be taking their first HIV test. In a logistic regression model, after
adjusting for these factors, using condoms in a stable relationship decreased the
odds of LTC by 72% (odds ratio 0.28; confidence interval 0.11-0.67). CONCLUSIONS:
Integration into care after HIV diagnosis requires improvement. Our results
suggest that broadening awareness and counselling about sexual risks may have a
positive impact.
PMID- 25123959
TI - Polycystin-1 and polycystin-2 are involved in the acquisition of aggressive
phenotypes in colorectal cancer.
AB - The polycystins PC1 and PC2 are emerging as major players in mechanotransduction,
a process that influences all steps of the invasion/metastasis cascade. We
hypothesized that PC1 and PC2 facilitate cancer aggressiveness. Immunoblotting,
RT-PCR, semi-quantitative and quantitative real-time PCR and FACS analyses were
employed to investigate the effect of polycystin overexpression in colorectal
cancer (CRC) cells. The impact of PC1 inhibition on cancer-cell proliferation was
evaluated through an MTT assay. In vitro data were analyzed by Student's t-test.
HT29 human xenografts were treated with anti-PC1 (extracellular domain)
inhibitory antibody and analyzed via immunohistochemistry to determine the in
vivo role of PC1 in CRC. Clinical significance was assessed by examining PC1 and
PC2 protein expression in CRC patients (immunohistochemistry). In vivo and
clinical data were analyzed by non-parametric tests, Kaplan-Meier curves, log
rank test and Cox model. All statistical tests were two-sided. PC1 overexpression
promotes epithelial-to-mesenchymal transition (EMT) in HCT116 cells, while PC2
overexpression results in upregulation of the mTOR pathway in SW480 cells. PC1
inhibition causes reduced cell proliferation in CRC cells inducing tumor necrosis
and suppressing EMT in HT29 tumor xenografts. In clinical study, PC1 and PC2
overexpression associates with adverse pathological parameters, including
invasiveness and mucinous carcinomas. Moreover, PC1 overexpression appears as an
independent prognostic factor of reduced recurrence-free survival (HR = 1.016, p
= 0.03) and lowers overall survival probability, while aberrant PC2 expression
predicts poor overall survival (p = 0.0468). These results support, for the first
time, a direct link between mechanosensing polycystins (PC1 and PC2) and CRC
progression.
PMID- 25123960
TI - FeCr2S4 in magnetic fields: possible evidence for a multiferroic ground state.
AB - We report on neutron diffraction, thermal expansion, magnetostriction,
dielectric, and specific heat measurements on polycrystalline FeCr2S4 in external
magnetic fields. The ferrimagnetic ordering temperatures TC ~ 170 K and the
transition at TOO ~ 10 K, which has been associated with orbital ordering, are
only weakly shifted in magnetic fields up to 9 T. The cubic lattice parameter is
found to decrease when entering the state below TOO. The magnetic moments of the
Cr- and Fe-ions are reduced from the spin-only values throughout the magnetically
ordered regime, but approach the spin-only values for fields >5.5 T. Thermal
expansion in magnetic fields and magnetostriction experiments indicate a
contraction of the sample below about 60 K. Below TOO this contraction is
followed by a moderate expansion of the sample for fields larger than ~4.5 T. The
transition at TOO is accompanied by an anomaly in the dielectric constant. The
dielectric constant depends on both the strength and orientation of the external
magnetic field with respect to the applied electric field for T < TOO. A linear
correlation of the magnetic-field-induced change of the dielectric constant and
the magnetic-field dependent magnetization is observed. This behaviour is
consistent with the existence of a ferroelectric polarization and a multiferroic
ground state below 10 K.
PMID- 25123961
TI - N-heterocyclic carbene, high oxidation state molybdenum alkylidene complexes:
functional-group-tolerant cationic metathesis catalysts.
AB - We synthesized the first N-heterocyclic carbene (NHC) complexes of Schrock's
molybdenum imido alkylidene bis(triflate) complexes. Unlike existing
bis(triflate) complexes, the novel 16-electron complexes represent metathesis
active, functional-group-tolerant catalysts. Single-crystal X-ray structures of
two representatives of this novel class of Schrock catalysts are presented and
reactivity is discussed in view of their structural peculiarities. In the
presence of monomer (substrate), these catalysts form cationic species and can be
employed in ring-closing metathesis (RCM), ring-opening metathesis polymerization
(ROMP), as well as in the cyclopolymerization of alpha,omega-diynes. Monomers
containing functional groups, which are not tolerated by the existing variations
of Schrock's catalyst, e.g., sec-amine, hydroxy, and carboxylic acid moieties,
can be used. These catalysts therefore hold great promise in both organic and
polymer chemistry, where they allow for the use of protic monomers.
PMID- 25123962
TI - Safe management of chronic pain in pregnancy in an era of opioid misuse and
abuse.
AB - Safe and effective management of chronic pain in pregnancy is challenging. Use of
over-the-counter analgesics, opioids, opioid substitution therapies,
complementary and alternative therapies, antidepressants, and anxiolytics each
have benefits and risks for the mother and neonate that must be considered.
Because of their potency, opioids are often used despite associated risks for
adverse effects, abuse, diversion, and addiction. Development of a pain
management protocol for the counsel and care of pregnant women with pain is
necessary.
PMID- 25123963
TI - Molecular profiling in fresh tissue with high tumor cell content promotes
enrichment for aggressive adenocarcinomas in cervix.
AB - Many emerging tools for comprehensive molecular profiling of malignant lesions
demand fresh frozen tissue with a high tumor purity. Often, a tumor epithelial
content of at least 80% is recommended. This approach may lead to a systematic
bias, and therefore we explore if this introduces a selection of cases with a
certain phenotype in cervical cancer. Clinicopathologic data for a population
based cohort of 328 patients have been studied. Fresh frozen tumor specimens were
available for 151 of these patients and investigated for epithelial tumor cell
portion in hematoxylin-stained frozen sections by light microscopy. The estimated
tumor purity in the samples was compared with FIGO stage, histopathologic
characteristics and survival. High tumor purity was significantly more often
found in squamous cell carcinoma (SCC) compared to adenocarcinoma (AC) (P=0.03).
For the subgroup of AC (n=40), there was a significant association between high
tumor purity in the fresh frozen samples and later occurrence of recurrent
disease (P=0.04). In SCC, no significant associations between tumor purity and
disease stage, grade or outcome were found. Apparently in line with this, grade
was found to influence prognosis in AC, but not in SCC. Our findings suggest that
selection of samples based on high tumor purity in fresh frozen tissue may
introduce a selection bias toward aggressive disease for the subgroup of AC, but
not for SCC of the cervix. Thus, the prevalence of potential molecular biomarkers
identified in AC in particular should be validated in a population-based setting
to further explore clinical relevance. Also, molecular biomarkers only prevalent
in subgroups with low tumor purity may go undetected in sample collections
enriched for high tumor purity.
PMID- 25123965
TI - Complete Genome Sequence of the Siphoviral Bacteriophage YMC/09/04/R1988 MRSA BP:
A lytic phage from a methicillin-resistant Staphylococcus aureus isolate.
AB - Methicillin-resistant Staphylococcus aureus (MRSA) is an increasing cause of
serious infection, both in the community and hospital settings. Despite
sophisticated strategies and efforts, the antibiotic options for treating MRSA
infection have been narrowed due to the limited number of newly developed
antimicrobials. Herein, we analyze the completely sequenced genome of a novel
virulent phage YMC/09/04/R1988 MRSA BP as a potential alternative anti-MRSA
agent, which lysed clinical isolates from a patient admitted to the hospital due
to hip disarticulation. The phage contains a linear double-stranded DNA genome of
44,459 bp in length, with 33.37% GC content, 62 predicted open reading frames
(ORFs), and annotated functions of only 23 ORFs that are associated with
structural assembly, host lysis, DNA replication, and modification. It showed a
broad host range (17 of 30 strains) against MRSA strains in clinical isolates.
This article is protected by copyright. All rights reserved.
PMID- 25123964
TI - Limited reliability of five non-invasive biomarkers in predicting hepatic
fibrosis in chronic HCV mono-infected patients opposed to METAVIR scoring.
AB - BACKGROUND: Liver biopsy is gold standard for fibrosis assessment in hepatitis C
virus (HCV) infection but its limitations led to the identification of non
invasive biomarkers. This study assesses the reliability of five biomarkers in
estimating the stage of liver fibrosis/cirrhosis in chronic HCV patients versus
METAVIR scoring. METHODS: One hundred HCV monoinfected patients who underwent
liver biopsy and blood sampling were included. Liver fibrosis was staged (F0-4)
and required laboratory tests were performed. AAR, API, APRI, FIB-4 and Pohl
score were calculated and their receiver operating curves (ROCs), sensitivities,
specificities, predictive values and accuracies were evaluated. RESULTS: There
were 27, 44, and 29 patients at F0-F1, F2-F3, and F4 groups. Significant
statistical differences were found regarding AST, vireamia, platelet count,
prothrombin time and all biomarkers. From ROCs only Pohl score predicted
significant fibrosis and cirrhosis but with low accuracy. AAR, API and APRI
showed moderate performance at low cut-offs, but had limited predictive values or
accuracies at higher cut-offs. FIB-4 was the least accurate test. The diagnostic
reliability of these biomarkers was limited to patients with suspected
insignificant fibrosis. CONCLUSIONS: This study verified the limited reliability
for AAR, API, APRI, FIB-4 and Pohl score in estimating the stage of hepatic
fibrosis in HCV infected patients opposed to METAVIR scoring.
PMID- 25123966
TI - Confounder selection via penalized credible regions.
AB - When estimating the effect of an exposure or treatment on an outcome it is
important to select the proper subset of confounding variables to include in the
model. Including too many covariates increases mean square error on the effect of
interest while not including confounding variables biases the exposure effect
estimate. We propose a decision-theoretic approach to confounder selection and
effect estimation. We first estimate the full standard Bayesian regression model
and then post-process the posterior distribution with a loss function that
penalizes models omitting important confounders. Our method can be fit easily
with existing software and in many situations without the use of Markov chain
Monte Carlo methods, resulting in computation on the order of the least squares
solution. We prove that the proposed estimator has attractive asymptotic
properties. In a simulation study we show that our method outperforms existing
methods. We demonstrate our method by estimating the effect of fine particulate
matter (PM2.5) exposure on birth weight in Mecklenburg County, North Carolina.
PMID- 25123967
TI - Dry-processable carbon nanotubes for functional devices and composites.
AB - Assembly of carbon nanotubes (CNTs) in effective and productive ways is of vital
importance to their application. Recent progress in synthesis of CNTs has
inspired new strategies for utilizing the unique physiochemical properties of
CNTs in macroscale materials and devices. Assembling CNTs by dry processes (e.g.,
directly collecting CNTs in the form of freestanding films followed by pressing,
stretching, and multilayer stacking instead of dispersing them in solution) not
only considerably simplifies the processes but also avoids structural damage to
the CNTs. Various dry-processable CNTs are reviewed, focusing on their synthesis,
properties, and applications. The synthesis techniques are organized in terms of
aggregative morphologies and microstructure control of CNTs. Important
applications such as functional thin-film devices, strong CNT films, and
composites are included. The opportunities and challenges in the synthesis
techniques and fabrication of advanced composites and devices are discussed.
PMID- 25123969
TI - [Update pediatric orthopedics].
PMID- 25123970
TI - [Orthopedics update: tumor orthopedics].
PMID- 25123968
TI - The validity of a behavioural multiple-mini-interview within an assessment centre
for selection into specialty training.
AB - BACKGROUND: Entry into specialty training was determined by a National Assessment
Centre (NAC) approach using a combination of a behavioural Multiple-Mini
Interview (MMI) and a written Situational Judgement Test (SJT). We wanted to know
if interviewers could make reliable and valid decisions about the non-cognitive
characteristics of candidates with the purpose of selecting them into general
practice specialty training using the MMI. Second, we explored the concurrent
validity of the MMI with the SJT. METHODS: A variance components analysis
estimated the reliability and sources of measurement error. Further modelling
estimated the optimal configurations for future MMI iterations. We calculated the
relationship of the MMI with the SJT. RESULTS: Data were available from 1382
candidates, 254 interviewers, six MMI questions, five alternate forms of a 50
item SJT, and 11 assessment centres. For a single MMI question and one assessor,
28% of the variance between scores was due to candidate-to-candidate variation.
Interviewer subjectivity, in particular the varying views that interviewer had
for particular candidates accounted for 40% of the variance in scores. The
generalisability co-efficient for a six question MMI was 0.7; to achieve 0.8
would require ten questions. A disattenuated correlation with the SJT (r = 0.35),
and in particular a raw score correlation with the subdomain related to clinical
knowledge (r = 0.25) demonstrated evidence for construct and concurrent validity.
Less than two per cent of candidates would have failed the MMI. CONCLUSION: The
MMI is a moderately reliable method of assessment in the context of a National
Assessment Centre approach. The largest source of error relates to aspects of
interviewer subjectivity, suggesting enhanced interviewer training would be
beneficial. MMIs need to be sufficiently long for precise comparison for ranking
purposes. In order to justify long term sustainable use of the MMI in a
postgraduate assessment centre approach, more theoretical work is required to
understand how written and performance based test of non-cognitive attributes can
be combined, in a way that achieves acceptable generalizability, and has
validity.
PMID- 25123971
TI - [springermedizin.de -- the editor recommends].
PMID- 25123972
TI - Lineage-specific evolution of cnidarian Wnt ligands.
AB - We have studied the evolution of Wnt genes in cnidarians and the expression
pattern of all Wnt ligands in the hydrozoan Hydractinia echinata. Current views
favor a scenario in which 12 Wnt sub-families were jointly inherited by
cnidarians and bilaterians from their last common ancestor. Our phylogenetic
analyses clustered all medusozoan genes in distinct, well-supported clades, but
many orthologous relationships between medusozoan Wnts and anthozoan and
bilaterian Wnt genes were poorly supported. Only seven anthozoan genes, Wnt2,
Wnt4, Wnt5, Wnt6, Wnt 10, Wnt11, and Wnt16 were recovered with strong support
with bilaterian genes and of those, only the Wnt2, Wnt5, Wnt11, and Wnt16 clades
also included medusozoan genes. Although medusozoan Wnt8 genes clustered with
anthozoan and bilaterian genes, this was not well supported. In situ
hybridization studies revealed poor conservation of expression patterns of
putative Wnt orthologs within Cnidaria. In polyps, only Wnt1, Wnt3, and Wnt7 were
expressed at the same position in the studied cnidarian models Hydra,
Hydractinia, and Nematostella. Different expression patterns are consistent with
divergent functions. Our data do not fully support previous assertions regarding
Wnt gene homology, and suggest a more complex history of Wnt family genes than
previously suggested. This includes high rates of sequence divergence and lineage
specific duplications of Wnt genes within medusozoans, followed by functional
divergence over evolutionary time scales.
PMID- 25123973
TI - Association of creative achievement with cognitive flexibility by a combined
voxel-based morphometry and resting-state functional connectivity study.
AB - Although researchers generally concur that creativity involves the production of
novel and useful products, the neural basis of creativity remains elusive due to
the complexity of the cognitive processes involved. Recent studies have shown
that highly creative individuals displayed more cognitive flexibility. However,
direct evidence supporting the relationship between creativity and cognitive
flexibility has rarely been investigated using both structural and functional
neuroimaging techniques. We used a combined voxel-based morphometry and resting
state functional connectivity (rsFC) analysis to investigate the relationship
between individual creativity ability assessed by the creative achievement
questionnaire (CAQ), and regional gray matter volume (GMV), as well as intrinsic
functional connectivity. Results showed that CAQ scores negatively correlated
with GMV in the rostral anterior cingulate cortex (ACC) and the bilateral dorsal
ACC (dACC) extending to supplementary motor area, but positively correlated with
GMV in the bilateral superior frontal gyrus and ventral medial prefrontal cortex
(vmPFC). Further functional connectivity analysis revealed that higher creative
achievement was inversely associated with the strength of rsFC between the dACC
and medial superior frontal gyrus (mSFG), right middle frontal gyrus, and left
orbito-frontal insula. Moreover, the association between the dACC-mSFG
connectivity and CAQ scores was mediated by cognitive flexibility, assessed by a
task-switching paradigm. These findings indicate that individual differences in
creative achievement are associated with both brain structure and corresponding
intrinsic functional connectivity involved in cognitive flexibility and
deliberate creative processing. Furthermore, dACC-mSFG connectivity may affect
creative achievement through its impact on cognitive flexibility.
PMID- 25123974
TI - Repetition probability effects for inverted faces.
AB - It has been shown, that the repetition related reduction of the blood-oxygen
level dependent (BOLD) signal is modulated by the probability of repetitions
(P(rep)) for faces (Summerfield et al., 2008), providing support for the
predictive coding (PC) model of visual perception (Rao and Ballard, 1999).
However, the stage of face processing where repetition suppression (RS) is
modulated by P(rep) is still unclear. Face inversion is known to interrupt higher
level configural/holistic face processing steps and if modulation of RS by P(rep)
takes place at these stages of face processing, P(rep) effects are expected to be
reduced for inverted when compared to upright faces. Therefore, here we aimed at
investigating whether P(rep) effects on RS observed for face stimuli originate at
the higher-level configural/holistic stages of face processing by comparing these
effects for upright and inverted faces. Similarly to previous studies, we
manipulated P(rep) for pairs of stimuli in individual blocks of fMRI recordings.
This manipulation significantly influenced repetition suppression in the
posterior FFA, the OFA and the LO, independently of stimulus orientation. Our
results thus reveal that RS in the ventral visual stream is modulated by P(rep)
even in the case of face inversion and hence strongly compromised
configural/holistic face processing. An additional whole-brain analysis could not
identify any areas where the modulatory effect of probability was orientation
specific either. These findings imply that P(rep) effects on RS might originate
from the earlier stages of face processing.
PMID- 25123975
TI - Comparison of long-term outcomes following traumatic injury: what is the unique
experience for those with brain injury compared with orthopaedic injury?
AB - OBJECTIVE: Whilst it has been well-demonstrated that traumatic brain injury (TBI)
results in long-term cognitive, behavioural and emotional difficulties, less is
understood about how these outcomes differ from those following traumatic
orthopaedic injury (TOI). The aim of this study was to compare self-reported
outcomes at 5-10 years post-injury for those with TBI, TOI, and uninjured
controls. It was hypothesised that participants with TBI would have greater
cognitive difficulties; participants with TOI and TBI would have similar
functional and physical outcomes, both being poorer than controls; and
participants with TBI would have poorer psychosocial outcomes than those with
TOI. PARTICIPANTS AND METHODS: Eighty-eight individuals with complicated mild to
severe TBI and 96 with TOI recruited during inpatient rehabilitation were
followed up 5-10 years post-injury, together with 48 controls followed over a
similar period. Self-report measures of global functioning (GOS-E), quality of
life (SF-36), psychological wellbeing (SCL-90-R, HADS, PCL-S), psychosocial
difficulties (SIP), cognitive difficulties (SF-36 COG), pain (BPI), and fatigue
(FSS) were administered. RESULTS: Outcomes for individuals with TBI and TOI
differed significantly from controls, with poorer global functioning, and greater
psychological distress and interference from pain. Only participants with TBI
reported greater cognitive difficulties and anxiety than controls, and were less
likely to be employed or in a relationship. Participants with TBI reported
greater anxiety, PTSD, psychological distress and psychosocial difficulties than
those with TOI. CONCLUSIONS: Both TOI and TBI cause long-term disability,
interference from pain, and psychological distress. However, cognitive
impairments, unemployment, lack of long-term relationships, anxiety and PTSD are
more substantial long-term problems following TBI. Findings from this study have
implications for managing risks associated with these injury groups and tailoring
rehabilitation to improve long-term outcomes.
PMID- 25123976
TI - Central 22q11.2 deletions.
AB - 22q11.2 deletion syndrome is one of the most common microdeletion syndromes. Most
patients have a deletion resulting from a recombination of low copy repeat blocks
LCR22-A and LCR22-D. Loss of the TBX1 gene is considered the most important cause
of the phenotype. A limited number of patients with smaller, overlapping
deletions distal to the TBX1 locus have been described in the literature. In
these patients, the CRKL gene is deleted. Haploinsufficiency of this gene has
also been implicated in the pathogenesis of 22q11.2 deletion syndrome. To
distinguish these deletions (comprising the LCR22-B to LCR22-D region) from the
more distal 22q11.2 deletions (located beyond LCR22-D), we propose the term
"central 22q11.2 deletions". In the present study we report on 27 new patients
with such a deletion. Together with information on previously published cases, we
review the clinical findings of 52 patients. The prevalence of congenital heart
anomalies and the frequency of de novo deletions in patients with a central
deletion are substantially lower than in patients with a common or distal 22q11.2
deletion. Renal and urinary tract malformations, developmental delays, cognitive
impairments and behavioral problems seem to be equally frequent as in patients
with a common deletion. None of the patients had a cleft palate. Patients with a
deletion that also encompassed the MAPK1 gene, located just distal to LCR22-D,
have a different and more severe phenotype, characterized by a higher prevalence
of congenital heart anomalies, growth restriction and microcephaly. Our results
further elucidate genotype-phenotype correlations in 22q11.2 deletion syndrome
spectrum.
PMID- 25123977
TI - Potential role of cinacalcet hydrochloride in sporadic primary
hyperparathyroidism without surgery indication.
PMID- 25123978
TI - Enzalutamide in European and North American men participating in the AFFIRM
trial.
AB - OBJECTIVE: To explore any differences in efficacy and safety outcomes between
European (EU) (n = 684) and North American (NA) (n = 395) patients in the AFFIRM
trial (NCT00974311). PATIENTS AND METHODS: Phase III, double-blind, placebo
controlled, multinational AFFIRM trial in men with metastatic castration
resistant prostate cancer (mCRPC) after docetaxel. Participants were randomly
assigned in a 2:1 ratio to receive oral enzalutamide 160 mg/day or placebo. The
primary end point was overall survival (OS) in a post hoc analysis. RESULTS:
Enzalutamide significantly improved OS compared with placebo in both EU and NA
patients. The median OS in EU patients was longer than NA patients in both
treatment groups. However, the relative treatment effect, expressed as hazard
ratio and 95% confidence interval, was similar in both regions: 0.64 (0.50, 0.82)
for EU and 0.63 (0.47, 0.83) for NA. Significant improvements in other end points
further confirmed the benefit of enzalutamide over placebo in patients from both
regions. The tolerability profile of enzalutamide was comparable between EU and
NA patients, with fatigue and nausea the most common adverse events. Four EU
patients (4/461 enzalutamide-treated, 0.87%) and one NA patient (1/263
enzalutamide-treated, 0.38%) had seizures. The difference in median OS was
related in part to the timing of development of mCRPC and baseline demographics
on study entry. CONCLUSION: This post hoc exploratory analysis of the AFFIRM
trial showed a consistent OS benefit for enzalutamide in men with mCRPC who had
previously progressed on docetaxel in both NA- and EU-treated patients, although
the median OS was higher in EU relative to NA patients. Efficacy benefits were
consistent across end points, with a comparable safety profile in both regions.
PMID- 25123980
TI - Cadmium and lead in chocolates commercialized in Brazil.
AB - Cadmium (Cd) and lead (Pb) concentrations and their relationship to the cocoa
content of chocolates commercialized in Brazil were evaluated by graphite furnace
atomic absorption spectrometry (GF AAS) after microwave-assisted acid digestion.
Several chemical modifiers were tested during method development, and analytical
parameters, including the limits of detection and quantification as well as the
accuracy and precision of the overall procedure, were assessed. The study
examined 30 chocolate samples, and the concentrations of Cd and Pb were in the
range of <1.7-107.6 and <21-138.4 ng/g, respectively. The results indicated that
dark chocolates have higher concentrations of Cd and Pb than milk and white
chocolates. Furthermore, samples with five different cocoa contents (ranging from
34 to 85%) from the same brand were analyzed, and linear correlations between the
cocoa content and the concentrations of Cd (R(2) = 0.907) and Pb (R(2) = 0.955)
were observed. The results showed that chocolate might be a significant source of
Cd and Pb ingestion, particularly for children.
PMID- 25123979
TI - Comparison of ARIMA and Random Forest time series models for prediction of avian
influenza H5N1 outbreaks.
AB - BACKGROUND: Time series models can play an important role in disease prediction.
Incidence data can be used to predict the future occurrence of disease events.
Developments in modeling approaches provide an opportunity to compare different
time series models for predictive power. RESULTS: We applied ARIMA and Random
Forest time series models to incidence data of outbreaks of highly pathogenic
avian influenza (H5N1) in Egypt, available through the online EMPRES-I system. We
found that the Random Forest model outperformed the ARIMA model in predictive
ability. Furthermore, we found that the Random Forest model is effective for
predicting outbreaks of H5N1 in Egypt. CONCLUSIONS: Random Forest time series
modeling provides enhanced predictive ability over existing time series models
for the prediction of infectious disease outbreaks. This result, along with those
showing the concordance between bird and human outbreaks (Rabinowitz et al.
2012), provides a new approach to predicting these dangerous outbreaks in bird
populations based on existing, freely available data. Our analysis uncovers the
time-series structure of outbreak severity for highly pathogenic avain influenza
(H5N1) in Egypt.
PMID- 25123981
TI - Increased ethanol production from sweet sorghum juice concentrated by a membrane
separation process.
AB - The aim of this investigation was to attain high ethanol concentration by
concentrating sweet sorghum juice using a two-step membrane separation process.
Ultrafiltration permeation of the juice was used to remove residues, followed by
nanofiltration concentration to increase the sugar concentration. The
concentrated juice containing 180.0 g L(-1) sucrose, 59.3 g L(-1) glucose and
49.3 g L(-1) fructose supplemented with nitrogen sources (10 and 20 g L(-1) of
yeast extract and polypeptone, respectively) was fermented by Saccharomyces
cerevisiae BY4741 to produce 133.5 g L(-1) of ethanol (87.6% of theoretical
yield) after 48 h fermentation. Importantly, the addition of lower concentrations
of exogenous nitrogen sources (3 and 6 g L(-1) of yeast extract and polypeptone,
respectively) or no exogenous nitrogen sources resulted in the production of
131.4 and 132.8 g L(-1) of ethanol (84.8% and 86.0% of theoretical yield),
respectively, after 48 h fermentation.
PMID- 25123982
TI - Physical pretreatments of wastewater algae to reduce ash content and improve
thermal decomposition characteristics.
AB - Previous study showed high ash content in wastewater algae (WA) has a negative
effect on bio-crude oil formation in hydrothermal liquefaction (HTL). This study
explored the effect of different pretreatments on ash reduction and the thermal
decomposition of WA. Single-stage (e.g. centrifugation) and two-stage
pretreatments (e.g. centrifugation followed by ultrasonication, C+U) were used.
The apparent activation energy of the thermal decomposition (E(a)) of pretreated
algae was determined. HTL was conducted to study how different pretreatments may
impact on bio-crude oil formation. Compared to untreated samples, the ash content
of algae with centrifugation was reduced from 28.6% to 18.6%. With C+U
pretreatments, E(a) was decreased from 50.2 kJ/mol to 35.9 kJ/mol and the bio
crude oil yield was increased from 30% to 55%. These results demonstrate that
pretreatments of C+U can improve the thermal decomposition behavior of WA and
enhance the bio-crude oil conversion efficiency.
PMID- 25123984
TI - Self-powered energy fiber: energy conversion in the sheath and storage in the
core.
AB - A high-performance, self-powered, elastic energy fiber is developed that consists
of an energy conversion sheath and an energy storage core. The coaxial structure
and the aligned nanostructures at the electrode interface enable a high total
energy-conversion and energy-storage performance that is maintained under bending
and after stretching.
PMID- 25123983
TI - Influence of health-related quality of life on health service utilization in
Chinese rural-to-urban female migrant workers.
AB - BACKGROUND: Rural-to-urban migrant workers have been increasing rapidly in China
over recent decades. Health related quality of life (HRQOL) may affect health
service utilization. There is a lack of data on HRQOL in relation to health
service utilization in Chinese rural-to-urban migrant workers. This study was
aimed to explore the influence of HRQOL on health service utilization in Chinese
rural-to-urban female migrant workers. METHODS: This was a cross-sectional survey
of 1,438 female rural-to-urban migrant workers in Shenzhen-Dongguan economic
zone, China in 2013. HRQOL was assessed by the 36-items Health Survey Short Form
(SF-36). Health service utilization was measured by any physician visit over the
recent two weeks and any hospitalization over the last 1-year (annual
hospitalization). Clustered logistic regression was used to analyze the influence
of HRQOL on health service utilization. RESULTS: Lower scores in three HRQOL
domains (bodily pain, general health, role physical) were associated with more
frequent health service utilization in female rural-to-urban migrant workers.
Bodily pain and general health were associated with an independent influence of
15.6% on the risk of recent two-week physician visit, while role physical and
general health were associated with an independent influence of 21.2% on the risk
of annual hospitalization. The independent influence of HRQOL on health service
utilization was smaller than that of socio-demographic and health-related
variables. CONCLUSIONS: HRQOL may have a modest influence on health service
utilization in Chinese rural-to-urban female migrant workers - an underprivileged
population in urban China.
PMID- 25123985
TI - Rates and risk factors associated with depressive symptoms during pregnancy and
with postpartum onset.
AB - The objectives of this study were to evaluate the prevalence of depressive
symptoms in the third trimester of pregnancy and at 3 months postpartum and to
prospectively identify risk factors associated with elevated depressive symptoms
during pregnancy and with postpartum onset. About 364 women attending antenatal
clinics or at the time of their ultrasound were recruited and completed
questionnaires in pregnancy and 226 returned their questionnaires at 3 months
postpartum. Depressed mood was assessed by the Edinburgh Postnatal Depression
Scale (EPDS; score of >= 10). The rate of depressed mood during pregnancy was
28.3% and 16.4% at 3 months postpartum. Among women with postpartum depressed
mood, 6.6% were new postpartum cases. In the present study, belonging to a non
Caucasian ethnic group, a history of emotional problems (e.g. anxiety and
depression) or of sexual abuse, comorbid anxiety, higher anxiety sensitivity and
having experienced stressful events were associated with elevated depressed mood
during pregnancy. Four risk factors emerged as predictors of new onset elevated
depressed mood at 3 months postpartum: higher depressive symptomatology during
pregnancy, a history of emotional problems, lower social support during pregnancy
and a delivery that was more difficult than expected. The importance of
identifying women at risk of depressed mood early in pregnancy and clinical
implications are discussed.
PMID- 25123986
TI - Reliability and validity of three shortened versions of the State Anxiety
Inventory scale during the perinatal period.
AB - The screening for anxiety in obstetric settings has been challenging due to time
and knowledge constraints. Brief, valid, and reliable instruments can provide
health care professionals with a quick and easy method to assess anxiety. Three
six-item forms of the State Anxiety Inventory scale have been constructed. The
purpose of this study was to evaluate and compare the psychometric properties of
these short versions in the perinatal period. Data were drawn from a longitudinal
pregnancy cohort in Alberta, Canada. Internal consistency of the shortened
versions was assessed. Confirmatory factor analysis was conducted to estimate and
compare indicators of fit during pregnancy and at 4 and 12 months postpartum. All
shortened scales demonstrated high internal consistency and reliability, with
alphas ranging from 0.81 to 0.85. All fit indices were greater than 0.93,
implying a good fit between each model and our data. In the model comparisons,
the Marteau and Bekker scale provided a more robust fit to data obtained during
pregnancy and the early postpartum period. At 12 months postpartum, the Chlan et
al. form demonstrated the best fit of the three versions. The shortened scales
appear to have acceptable psychometric properties. Brief scales have the
potential to provide an economical means of assessing perinatal anxiety and can
be considered as equivalent alternatives to the full-scale version.
PMID- 25123988
TI - Effect of deodorant and antiperspirant use and presence or absence of axillary
hair on absorption of testosterone 2% solution applied to men's axillae.
AB - INTRODUCTION: Testosterone 2% solution is applied to axillae and is indicated for
testosterone replacement therapy in males deficient in endogenous testosterone.
AIM: This open-label crossover study evaluated the effect of
deodorant/antiperspirant use and presence or absence of axillary hair on
absorption of testosterone solution. METHODS: Healthy males (N = 30; >=50 years
of age with baseline testosterone <400 ng/dL) were randomized to one of four
treatment sequences involving six treatments. Each treatment consisted of one 1.5
mL dose of testosterone 2% solution (30 mg of testosterone) applied to each
axilla. Axillae were unshaved or shaved, and were untreated or pretreated with
deodorant/antiperspirant. MAIN OUTCOME MEASURES: Blood samples were taken over 72
hours after each dose for measuring serum testosterone concentrations. RESULTS:
Profiles of mean testosterone concentrations were similar across treatments. For
all treatments, area under the concentration-time curve through 24 hours (AUC[0
24] ) and 72 hours (AUC[0-72] ), and maximum total testosterone concentration
(Cmax ) were similar except for 15% lower Cmax when treatment was applied after
deodorant/antiperspirant to shaved vs. unshaved axillae (least squares mean, 531
ng/dL vs. 626 ng/dL, respectively; P = 0.011). This difference is not considered
clinically significant. The 95% confidence intervals for AUC(0-24) , AUC(0-72) ,
and Cmax fell within the traditional bioequivalence limits of 0.8 to 1.25.
Incidence of treatment-emergent adverse events (TEAEs) was low (<15%) in each
treatment arm, and most TEAEs were mild. CONCLUSIONS: Absorption of testosterone
2% solution was unaffected by use of deodorant/antiperspirant or by the presence
or absence of axillary hair. Testosterone solution was generally well tolerated.
PMID- 25123987
TI - Speech perception and production by sequential bilingual children: a longitudinal
study of voice onset time acquisition.
AB - The majority of bilingual speech research has focused on simultaneous bilinguals.
Yet, in immigrant communities, children are often initially exposed to their
family language (L1), before becoming gradually immersed in the host country's
language (L2). This is typically referred to as sequential bilingualism. Using a
longitudinal design, this study explored the perception and production of the
English voicing contrast in 55 children (40 Sylheti-English sequential bilinguals
and 15 English monolinguals). Children were tested twice: when they were in
nursery (52-month-olds) and 1 year later. Sequential bilinguals' perception and
production of English plosives were initially driven by their experience with
their L1, but after starting school, changed to match that of their monolingual
peers.
PMID- 25123989
TI - The impact of an antimicrobial stewardship programme on the use of antimicrobials
and the evolution of drug resistance.
AB - Misuse of antibiotics can provoke increased bacterial resistance. There are no
immediate prospects of any new broad-spectrum antibiotics, especially any with
activity against enterobacteria, coming onto the market. Therefore, programmes
should be implemented to optimise antimicrobial therapy. In a quasi-experimental
study, the results for the pre-intervention year were compared with those for the
3 years following the application of an antimicrobial stewardship programme. We
describe 862 interventions carried out as part of the stewardship programme at
the Hospital Costa del Sol from 2009 to 2011. We examined the compliance of the
empirical antimicrobial treatment with the programme recommendations and the
treatment optimisation achieved by reducing the antibiotic spectrum and adjusting
the dose, dosing interval and duration of treatment. In addition, we analysed the
evolution of the sensitivity profile of the principal microorganisms and the
financial savings achieved. 93 % of the treatment recommendations were accepted.
The treatment actions taken were to corroborate the empirical treatment (46 % in
2009 and 31 % in 2011) and to reduce the antimicrobial spectrum taking into
account the antibiogram results (37 % in 2009 and 58 % in 2011). The main drugs
assessed were imipenem/meropenem, used in 38.6 % of the cases, and cefepime (20.1
%). The sensitivity profile of imipenem against Pseudomonas aeruginosa increased
by 10 % in 2011. Savings in annual drug spending (direct costs) of 30,000 Euros
were obtained. Stewardship programmes are useful tools for optimising
antimicrobial therapy. They may contribute to preventing increased bacterial
resistance and to reducing the long-term financial cost of antibiotic treatment.
PMID- 25123990
TI - Design of a metal-promoted oxide catalyst for the selective synthesis of
butadiene from ethanol.
AB - The synthesis of buta-1,3-diene from ethanol has been studied over metal
containing (M=Ag, Cu, Ni) oxide catalysts (MO(x)=MgO, ZrO2, Nb2O5, TiO2, Al2O3)
supported on silica. Kinetic study of a wide range of ethanol conversions (2-90%)
allowed the main reaction pathways leading to butadiene and byproducts to be
determined. The key reaction steps of butadiene synthesis were found to involve
ethanol dehydrogenation, acetaldehyde condensation, and the reduction of
crotonaldehyde with ethanol into crotyl alcohol. Catalyst design included the
selection of active components for each key reaction step and merging of these
components into multifunctional catalysts and adjusting the catalyst functions to
achieve the highest selectivity. The best catalytic performance was achieved over
the Ag/ZrO2/SiO2 catalyst, which showed the highest selectivity towards butadiene
(74 mol%).
PMID- 25123991
TI - Investigation of the immunogenicity of different types of aggregates of a murine
monoclonal antibody in mice.
AB - PURPOSE: The potential contribution of protein aggregates to the unwanted
immunogenicity of protein pharmaceuticals is a major concern. In the present
study a murine monoclonal antibody was utilized to study the immunogenicity of
different types of aggregates in mice. Samples containing defined types of
aggregates were prepared by processes such as stirring, agitation, exposure to
ultraviolet (UV) light and exposure to elevated temperatures. METHODS: Aggregates
were analyzed by size-exclusion chromatography, light obscuration, turbidimetry,
infrared (IR) spectroscopy and UV spectroscopy. Samples were separated into
fractions based on aggregate size by asymmetrical flow field-flow fractionation
or by centrifugation. Samples containing different types and sizes of aggregates
were subsequently administered to C57BL/6 J and BALB/c mice, and serum was
analyzed for the presence of anti-IgG1, anti-IgG2a, anti-IgG2b and anti-IgG3
antibodies. In addition, the pharmacokinetic profile of the murine antibody was
investigated. RESULTS: In this study, samples containing high numbers of
different types of aggregates were administered in order to challenge the in vivo
system. The magnitude of immune response depends on the nature of the aggregates.
The most immunogenic aggregates were of relatively large and insoluble nature,
with perturbed, non-native structures. CONCLUSION: This study shows that not all
protein drug aggregates are equally immunogenic.
PMID- 25123993
TI - Smoking, behavioral factors and familial environment: a population based study
with Brazilian adolescents.
AB - OBJECTIVE: The aim of the present study was to assess the association between
smoking and both behavioral and environmental factors among adolescents in the
public school system in the city of Campina Grande (northeastern Brazil).
METHODS: An analytical cross-sectional study was carried out involving 574
schoolchildren between 10 and 19 years, with the use of a structured
questionnaire addressing behavioral factors, environmental factors and smoking.
The chi-squared test and Fisher's exact test were used for the statistical
analysis (5 % level of significance). RESULTS: The prevalence of smoking was de
3.3 %. The lowest age regarding the use of tobacco for the first time was eight
years and the age group with the greatest frequency of initiation into this habit
was 11 to 14 years (44.3 %). A total of 84.3 % of tobacco users smoked between
one and 10 cigarettes per day. Smoking was associated with delays in schooling
(p=0.047), gender (p=0.016), alcohol use and frequency of alcohol use (p<0.001)
and the relationship with one's father (p=0.014) and mother (p=0.004).
CONCLUSIONS: Despite the low prevalence, an early initiation into smoking was
found, suggesting that educational campaigns should be directed at earlier ages.
Alcohol use stood out among the variables studied, suggesting that smoking is
influenced by both the use and intensity of this substance.
PMID- 25123992
TI - [Labour factors associated with post-traumatic stress in uniformed workers in
Medellin].
AB - OBJECTIVE: Determining the labor factors associated with post-traumatic stress in
uniformed workers in Medellin. METHOD: A cross-sectional study was made of 124
uniformed workers aged 20 to 48 years-old. A survey was made using an adults'
post-traumatic stress instrument which had been validated in Medellin.
Statistical analysis was carried out. RESULTS: Post-traumatic stress disorder
risk prevalence was 52.2 %. Multivariate analysis showed that the highest risk
situations were those related to previous mental health diagnosis (PR=7.67),
working schedule (4.24), violent episodes (PR=3.59) and community relationships
(PR=2.73). CONCLUSIONS: A person's current labor situation seemed to be a risk
factor for developing post-traumatic stress in the target population.
PMID- 25123994
TI - [The 20th century legal framework regarding risk at work and occupational health
in Colombia].
AB - OBJECTIVE: Analyzing the 20th century Colombian legal framework from the point of
view of labor law, social security and public health for identifying concepts
regarding occupational health and professional risk and trying to establish
convergence and differences between such foci and whether they fulfilled a
complementary view. METHOD: This work involved documentary research by means of
thematic categorical analysis of the laws and statutes promulgated in 20th
century Colombia, considering the main element or entity which should have
regulated that related to professional risk or occupational health. RESULTS: The
development of the 20th century Colombian legal framework regarding health at
work was periodized, revealing the predominance of a view of social law focused
on protecting dependent workers' work-related risks, as part of a tendency
extending to the Colombian Sistema General de Riesgos Laborales. CONCLUSIONS: The
proposed stages used for organizing the legal framework concerning social
security regarding professional risk and occupational health facilitated some
important elements being recognized concerning the social, legal and
institutional context from which workers' health laws emerged. Tension was noted
concerning statutes orientated towards redress and compensation regarding
accidents at work and legislation emphasizing prevention.
PMID- 25123995
TI - [A case study regarding the technical and public health feasibility of collecting
water from fog].
AB - OBJECTIVES: Evaluating the collection of water for human consumption from fog
nets in San Antonio (Cundinamarca department). METHOD: Water was collected from
fog using a prototype 6 m2sensor unit which was installed In the area for 53
days; this water was analysed to assess its quality regarding human consumption.
RESULTS: The collection area's average daily volume was 43.26 L/day and the
parameters evaluated met the minimum values established by local regulations for
drinking water (RAS 2000), except for pH. CONCLUSION: This technique represents
an alternative for obtaining water fit for human consumption and can be scaled-up
to produce the quantity needed for communities living in low rainfall areas. It
can thereby lead to improving such populations' health conditions. Its economic
feasibility should thus be assessed regarding its implementation and
sustainability.
PMID- 25123996
TI - [Factors associated with exclusive breastfeeding until the sixth month in teenage
mothers. Medellin, 2010].
AB - OBJECTIVE: Ascertaining factors associated with exclusive breastfeeding until the
sixth month in teenage mothers included in SISBEN system levels I and II in the
city of Medellin. METHODOLOGY: This was a case-control study which included 323
teenage mothers, involving 197 cases and 126 controls for the "Buen comienzo
habia una vez -BCHV" (good start) strategy. Univariate analysis involved using
descriptive statistics; a correspondence analysis was also made. Qualitative
variables were compared using contingency tables and the Mann-Whitney U test was
used for quantitative variables having non-normal distribution. Logistic
regressions was used to identify factors associated with exclusive breastfeeding
until the sixth month. Kapplan-Meier curves were made for the duration of
breastfeeding and for the significant variable in the model. The attributable
risk to which the population was exposed was calculated, as were population
attributable risks. RESULTS: 27.9% of teenage mothers in the sample managed
exclusive breastfeeding until the sixth month. Average maternal age was 17.56
years. Logistic regression analysis revealed that the time spent involved in the
strategy and education following the birth of a child for those belonging to a
nuclear family were associated with a longer duration of breastfeeding.
CONCLUSIONS: The duration of exclusive breastfeeding in the teenage mother
population could be extended, emphasizing continuity and the type of education
received by being in the program.
PMID- 25123997
TI - [Validating abbreviated developmental scale (ADS-1) criterion in the language
hearing domain].
AB - OBJECTIVE: Establishing the validity of abbreviated developmental scale (ADS
1)criterion, regarding the language and hearing domain for 4- to 5-year-old
children in the city of Popayan(2012). METHODS: This work involved a validation
study of diagnostic tests for 96 children whose language and hearing were
assessed by ADS-1 within a growth and development program and through speech
therapy assessment as gold standard (Reynell norm-referenced test for measuring
expressive and receptive language skills and tone audiometry and otoacoustic
emissions for assessing hearing). The validity of the scale?s criterion was
determined as was the correlation between both tests using the Kappa value. SPSS
19 was used for analyzing the results. RESULTS: The ADS-1 scale had 54 %
sensitivity, 42 % specificity, 87 %positive predictive value, 11 % negative
predictive value and K=-0.0 concordance. CONCLUSIONS: The ADS-1 scale has little
predictive ability for correctly classifying a patient as being really ill and/or
the healthy as being really sound. This value did not coincide with the
prevalence found (87.5%). Poor agreement between both methods did not allow it to
be classified as a valid instrument for use as a screening test for the early
detection of language and hearing disorders in children aged 4 to 5 years old.
PMID- 25123998
TI - Health risk represented by inhaling polycyclic aromatic hydrocarbons (PAH) during
daily commuting involving using a high traffic flow route in Bogota.
AB - OBJECTIVE: Assessing the risk to health by inhaling particles and particle-bound
PAH during daily commuting along a high traffic flow route/corridor in Bogota.
METHODS: A van was equipped with a PAS2000 photo-electric sensor for real-time
measurement of particle-bound PAH and a Dust Trakfor monitoring PM10
concentration; it drove along typical commuting routes in the city. Exposure to
particles and particle-bound PAH was assessed by using an inhalation intake
model. RESULTS: A similar trend was observed for both PM10 and PAH concentration,
indicating that traffic was the same source for both contaminants. Extreme PM10
and PAH inhalation concentrations were recorded every time direct bus and
microbus emissions were measured by the van. Inhalation model results indicated
that exposure was significantly greater when using a venues having mixed traffic
use (i.e. buses, microbuses, passenger vehicles, motorcycles) compared to using
roads where the TransMilenio system (articulated buses) had been implemented.
CONCLUSIONS: The results may support evaluating bus drivers, commuters and bike
users' exposure to toxic compounds in the city.
PMID- 25123999
TI - [Respiratory disease risk factors in the 5-14 year-old population in an area of
Bogota, 2012-2013].
AB - OBJECTIVE: Establishing the prevalence of respiratory symptoms, asthma and
rhinitis, possibly associated with air pollution, in 5- to 14-year-old children
in Bosa (a conurbation of Bogota), between 2012 and 2013. METHODS: A sample was
taken of 553 children living in the conurbation. RESULTS: The results indicated
that when a child lives with people who smoke there was a 1.5 times risk of
coughing at night (compared to living in a non-smoking home) such night-time
coughing being different to that produced by respiratory infections such as
colds, bronchitis and pneumonia. Children living in homes having fireplaces/open
cooking areas located less than 100 m apart had 1.6 times greater probability of
presenting symptoms. Children attending schools having greater PM10 exposure and
living near buildings being constructed or having roads in a poor state of repair
less than 100 meters from their homes were 2.5 times more likely to suffer
respiratory disease. Children living in damp rooms were 4 times more likely to
have wheezed during the past year. The risk of wheezing became increased by 80 %
when a child lived within 100 meters of buildings being constructed or near
unpaved roads and attended a school having greater exposure. CONCLUSION:
Government intervention is critical for changing respiratory disease-associated
extramural risk factors, such as improvements benefitting children which should
be carried out in urban areas.
PMID- 25124000
TI - [The lack of water and its implications regarding feeding practice in Turbo,
Antioquia].
AB - OBJECTIVE: Describing water-related perceptions and practice and how slum
dwellers lacking public service coverage in the town of Turbo in the Antioquia
Department, Colombia, approach this. METHODS: This study involved qualitative
research from an ethnographic approach. Data was collected by means of interviews
with slum dwellers and observing water-related activities. The information was
encoded; empirical categories were initially constructed, followed by analytical
ones. RESULTS: The families had established daily dynamics for facing life
without water, investing time, money and effort and, according to their
perceptions and possibilities, defining practice and uses for the water which
they had access to. The available water sources consisted of a piped water supply
which had to be paid for or was collected from other neighborhoods (considered
unsuitable for drinking), rain water (appreciated for its taste and alleged
quality) and bought bottled water (considered suitable for drinking and cooking,
but more expensive than the piped water). Less suitable water sources were
resorted to at critical moments during shortage. Regarding such deficiency,
feeding practice became modified by replacing preparations requiring more water
and making adjustments, thereby limiting what could be considered as suitable
feeding. CONCLUSIONS: The lack of water affected the target families' food
security, quality of life and welfare. Water-related practice corresponded to
living conditions, meaning that biological and social aspects must be reconciled
and recognized. The importance of the right to water and taking those suffering
such deficiency in to consideration when making public health policy was thus
highlighted.
PMID- 25124001
TI - [The congenital syphilis protocol used at the Instituto Materno Infantil-Hospital
la Victoria, Bogota].
AB - OBJECTIVES: Examining a cohort of women having a reactive venereal disease
research laboratory (VDRL) test on delivery (and their newborn) to describe
adherence to the Colombian treatment regime to prevent congenital syphilis and
identify adverse clinical outcomes. METHODOLOGY: A descriptive study of 73
pregnant women and their new born was carried out at the Instituto Materno
Infantil-Hospital La Victoria during 2008. RESULTS: Syphilis was detected in 50
women during their pregnancy and 23 when giving birth; 34 % became re-infected.
29 % were drug addicts, 19 % indigent and 23% had a history of syphilis. 7 cases
were considered successful regarding antenatal treatment. Congenital syphilis
frequency at the institution was 1 case per 46 births; there were 8 fetal deaths
(12 %) and 58 cases of congenital syphilis in the newborn (27 symptomatic and 31
asymptomatic). 7 newborn had neurosyphilis, 17 suffered growth restriction and 6
were premature. Attending antenatal care, detecting syphilis during pregnancy and
providing some type of treatment were related to decreased mortality, fewer
symptomatic newborn and fewer infants having IUGR. Pregnant female drug addicts
did not attend or lacked prenatal care and had a greater number of symptomatic
newborn, involving growth restriction and being premature. CONCLUSIONS: It is
recommended that pregnant women be encouraged to attend prenatal care and that
health personnel should become involved in detecting the disease, verifying
treatment in couples (i.e. including the sexual partner)and training in the
institution's maternal and neonatal care programs.
PMID- 25124002
TI - [Pharmacosurveillance regarding Colombian patients being treated with stavudine].
AB - OBJECTIVES: Reducing the occurrence of negative stavudine use-associated outcomes
by reporting such risk to doctors responsible for the care of HIV/AIDS patients
in Colombia as stavudine has been associated with cumulative and irreversible
toxicity. METHODS: All stavudine users were identified from Audifarma S.A. (drug
suppliers) databases (covering about 4.5 million people). The risk was then
reported to health service providers and the substitution of stavudine for
zidovudine or tenofovir was recommended. RESULTS: It was found that 1,410
patients registered in the afore mentioned databases were receiving
antiretroviral therapy during 2010, of whom 109 (7.5 %) were receiving stavudine;
these patients were living in 20 cities and being attended by 19 institutions.
Stavudine use became reduced by 94.6 % during the 28 months following the
intervention. Zidovudine was the most commonly used replacement drug. DISCUSSION:
Stavudine was successfully replaced following World Health Organization
recommendations aimed at preventing the occurrence of lipodystrophy and the
peripheral neuropathy associated with its use.
PMID- 25124003
TI - [Argentinean general practitioners' practice and counseling regarding physical
activity].
AB - OBJECTIVE: Investigating general practitioners' (GP) physical activity and to
what extent their own physical activity affects counselling their patients in
clinical practice. METHODOLOGY: This was a cross-sectional, exploratory study;
sample size was 115 (82 women and 33 men). The survey involved using a self
administered questionnaire at the GPs' annual congress in 2011, using a specially
designed, on-line questionnaire. RESULTS: This questionnaire revealed that about
76% of the female GPs did give advice concerning physical activity to their
patients while the respective prevalence in men was 33 %. Regarding advice
concerning physical activity to patients having non-communicable diseases, 73 %
of women GPs always seemed to recommend physical activity for them while the
corresponding prevalence in men was 27 %. Around 97 % (n=62) of the female GPs
and 93 % (n=25) of male GPs asked their patients about their physical activity
pattern; however, this study revealed that only 35 % (n=23) of male and 46 %
(n=12) of female GPS were actually familiar with the latest recommendations
concerning physical activity. CONCLUSION: No relationship was found between GPs'
physical activity level and their counselling in practice concerning physical
activity or their current knowledge of the topic. The study showed that GPs
stated that physical activity was important for their patients, although few of
them engaged in types of physical activity during their leisure-time. There would
thus seem to be an urgent need for training GPs in prescribing physical activity
at primary healthcare level to increase their patients' involvement in some form
of physical activity.
PMID- 25124004
TI - [A glossary for health care promoting universities (an HPU glossary)].
AB - The health promotion in the university context emerges as an important initiative
to facilitate the development of healthy lifestyle behaviors in this environment
where students, faculty and university staff spend and share a significant part
of their lives. The movement of Health Promoting Universities (HPU) has over 20
years of experience, but still lacks a common language that allows effective
communication between those who are interested in its planning and
implementation. The purpose of this paper is to develop the most relevant
concepts in the context of the international movement of UPS. This document is
organized into five anchor dimensions: [1]The university and health promotion,
[2] The University and its social responsibility, [3] The University, inequality
and inequity, [4] The University and evidence in health promotion, and [5]
Strategies to develop a HPU. It is hoped that this glossary for HPU encourages
the development of a common language between those who promote this initiative
and come from different disciplines, and at the same time serve as a guide for
practice.
PMID- 25124005
TI - [Causes of diabetic patients' indifference towards treatment, diet and monitoring
and possible factors associated with such disease].
AB - OBJECTIVES: Analyze the causes of detachment to diet and treatment of patients
with diabetes and factors associated with disease such as family history of
diabetes and hypertension, in patients from one municipality of San Luis Potosi,
Mexico, and surrounding areas. METHODS: Descriptive study of variables such as
age, sex, schooling level, occupation, family history of diabetes and
hypertension, causes of detachment to diet and treatment; analytic for groups in
terms of the risk of diabetes according to socio demographic and family history.
RESULTS: Of the 156 patients included main causes of detachment or abandonment of
the indicated treatment and/or were the oblivion and insistence on restricted
food intake. Patients with a family history of hypertension in both parents had
5.8 times the risk of Diabetes Mellitus, compared to those without this history
(p<0.01). Those patients with a maternal history of diabetes had 4.76 times the
risk of suffering it too, compared to those with only paternal history (p<0.001).
For patients with a history of obesity, they had 2.4 times higher risk of
developing diabetes than those who had not (p<0.05). CONCLUSIONS: Main causes,
reported by patients, for detachment to treatment and diet were the oblivion and
the insistence on restricted food intake, and the degree of association of
Diabetes Mellitus with family history of this disease and hypertension is 2.4 to
5.8 times, with p<0.05.
PMID- 25124007
TI - The heart of the matter: prime time E/e' prime!
PMID- 25124006
TI - Determination of glutamate dehydrogenase activity and its kinetics in mouse
tissues using metabolic mapping (quantitative enzyme histochemistry).
AB - Glutamate dehydrogenase (GDH) catalyses the reversible conversion of glutamate
into alpha-ketoglutarate with the concomitant reduction of NAD(P)(+) to NAD(P)H
or vice versa. GDH activity is subject to complex allosteric regulation including
substrate inhibition. To determine GDH kinetics in situ, we assessed the effects
of various glutamate concentrations in combination with either the coenzyme
NAD(+) or NADP(+) on GDH activity in mouse liver cryostat sections using
metabolic mapping. NAD(+)-dependent GDH V(max) was 2.5-fold higher than NADP(+)
dependent V(max), whereas the K(m) was similar, 1.92 mM versus 1.66 mM, when
NAD(+) or NADP(+) was used, respectively. With either coenzyme, V(max) was
determined at 10 mM glutamate and substrate inhibition was observed at higher
glutamate concentrations with a K(i) of 12.2 and 3.95 for NAD(+) and NADP(+) used
as coenzyme, respectively. NAD(+)- and NADP(+)-dependent GDH activities were
examined in various mouse tissues. GDH activity was highest in liver and much
lower in other tissues. In all tissues, the highest activity was found when
NAD(+) was used as a coenzyme. In conclusion, GDH activity in mice is highest in
the liver with NAD(+) as a coenzyme and highest GDH activity was determined at a
glutamate concentration of 10 mM.
PMID- 25124008
TI - Coronary involvement in lupus patients: getting sharper pictures with advanced
vascular imaging?
PMID- 25124009
TI - Contrast-enhanced CMR imaging of ventricular tachycardia isthmus sites to guide
ablation: an approach in evolution.
PMID- 25124010
TI - Does neointimal characterization following DES implantation predict long-term
outcomes?
PMID- 25124011
TI - Robot-assisted remote echocardiographic examination and teleconsultation: a
randomized comparison of time to diagnosis with standard of care referral
approach.
AB - The strategy using cardiological consultation in addition to the robot-assisted
remote echocardiography at a distance was tested in a prospective, randomized
open-label trial to evaluate its feasibility and to define its clinical value in
a rural area. The present study involved 1 primary healthcare center in the north
of Sweden, 135 miles from the hospital where the echocardiograms and the
cardiology teleconsultation were performed long distance in real time. Nineteen
patients were randomized to remote consultation and imaging, and 19 to the
standard of care consultation. The total process time was significantly reduced
in the former arm (median 114 days vs. 26.5 days; p < 0.001). The time from
randomization until attaining a specialist consultation was also significantly
reduced (p < 0.001). The patients' satisfaction was reassuring; they considered
that the remote consultation strategy offered an increased rapidity of diagnosis
and the likelihood of receiving faster management compared with the standard of
care at the primary healthcare center.
PMID- 25124012
TI - Feasibility of intercity and trans-Atlantic telerobotic remote ultrasound:
assessment facilitated by a nondedicated bandwidth connection.
AB - We discuss the concept of ultrasound imaging at a distance by presenting the
evaluation of a customized, lightweight, human-safe robotic arm for low-force,
long-distance, telerobotic ultrasonography. We undertook intercity and trans
Atlantic telerobotic ultrasound simulation from master stations located in New
York, New York and Munich, Germany, and imaged a phantom and a human volunteer
located at a slave station in Burlington, Massachusetts, using standard Internet
bandwidth <100 Mbps and <50 Mbps, respectively. The data from the robotic arm
were tracked for understanding the time efficiency of the human interactions at
the master stations. Comparison of a beginner in ultrasound operation with a
professional sonographer revealed that although proficiency in using ultrasound
was not a prerequisite for operating the robotic arm, previous experience in
using clinical ultrasound was associated with progressively lower probe
maneuvering time and speed due to an enhanced ability of the veteran operator in
adjusting the finer angular motions of the probe. These results suggest that long
distance telerobotic echocardiography over a local nondedicated Internet
bandwidth is feasible and can be rapidly learned by sonographers for cost
effective resource utilization.
PMID- 25124013
TI - Remote ultrasound: new opportunities.
PMID- 25124014
TI - Ultrafast cardiac ultrasound imaging: technical principles, applications, and
clinical benefits.
AB - Several recent technical advances in cardiac ultrasound allow data to be acquired
at a very high frame rate. Retrospective gating, plane/diverging wave imaging,
and multiline transmit imaging all improve the temporal resolution of the
conventional ultrasound system. The main drawback of such high frame rate data
acquisition is that it typically has reduced image quality. However, for given
clinical applications, the acquisition of temporally-resolved data might outweigh
the reduction in image quality. It is the aim of this paper to provide an
overview of the technical principles behind these new ultrasound imaging
modalities, to review the current evidence of their potential clinical added
value, and to forecast how they might influence daily clinical practice.
PMID- 25124016
TI - FDG PET/CT imaging for LVAD associated infections.
PMID- 25124017
TI - OCT imaging for the management of pulmonary hypertension.
PMID- 25124018
TI - Delayed disruption of a bioresorbable vascular scaffold.
PMID- 25124015
TI - Noninvasive imaging of cardiovascular injury related to the treatment of cancer.
AB - The introduction of multiple treatments for cancer, including chemotherapeutic
agents and radiation therapy, has significantly reduced cancer-related morbidity
and mortality. However, these therapies can promote a variety of toxicities,
among the most severe being the ones involving the cardiovascular system.
Currently, for many surviving cancer patients, cardiovascular (CV) events
represent the primary cause of morbidity and mortality. Recent data suggest that
CV injury occurs early during cancer treatment, creating a substrate for
subsequent cardiovascular events. Researchers have investigated the utility of
noninvasive imaging strategies to detect the presence of CV injury during and
after completion of cancer treatment because it starts early during cancer
therapy, often preceding the development of chemotherapy or cancer therapeutics
related cardiac dysfunction. In this State-of-the-Art Paper, we review the
utility of current clinical and investigative CV noninvasive modalities for the
identification and characterization of cancer treatment-related CV toxicity.
PMID- 25124019
TI - Integrated 3D Echo-X-Ray navigation to predict optimal angiographic deployment
projections for TAVR.
PMID- 25124021
TI - Reply: Effects of blood T1 on extracellular volume calculation.
PMID- 25124020
TI - Effects of blood T1 on extracellular volume calculation.
PMID- 25124022
TI - Why, when, and how often?: The next steps after defining the right tools for
noninvasive imaging of cardiotoxicity.
PMID- 25124023
TI - Adapting to a changing health care environment.
PMID- 25124024
TI - Stochastic population forecasting based on combinations of expert evaluations
within the Bayesian paradigm.
AB - This article suggests a procedure to derive stochastic population forecasts
adopting an expert-based approach. As in previous work by Billari et al. (2012),
experts are required to provide evaluations, in the form of conditional and
unconditional scenarios, on summary indicators of the demographic components
determining the population evolution: that is, fertility, mortality, and
migration. Here, two main purposes are pursued. First, the demographic components
are allowed to have some kind of dependence. Second, as a result of the existence
of a body of shared information, possible correlations among experts are taken
into account. In both cases, the dependence structure is not imposed by the
researcher but rather is indirectly derived through the scenarios elicited from
the experts. To address these issues, the method is based on a mixture model,
within the so-called Supra-Bayesian approach, according to which expert
evaluations are treated as data. The derived posterior distribution for the
demographic indicators of interest is used as forecasting distribution, and a
Markov chain Monte Carlo algorithm is designed to approximate this posterior.
This article provides the questionnaire designed by the authors to collect expert
opinions. Finally, an application to the forecast of the Italian population from
2010 to 2065 is proposed.
PMID- 25124025
TI - Is tissue oxygen saturation related with complete blood parameters in ED
patients?
PMID- 25124026
TI - Cardiology clinic follow-up did not decrease return visits to the ED for chest
pain patients.
AB - BACKGROUND: We initiated a program to rapidly rule out myocardial infarction and
make an appointment (with no co-payment) with a cardiologist within 72 hours for
patients with low-risk chest pain. OBJECTIVE: The objectives of this study were
to determine if the rate of return emergency department (ED) visits for chest
pain decreased among patients who kept their appointments and to evaluate factors
that impacted clinic no-show rates. METHODS: The study was conducted at a safety
net facility with 65 000 adult patient visits per year. This study was a
retrospective review of patients with chest pain discharged from the ED with a
scheduled cardiology clinic appointment between October 2008 and December 2009.
We compared those who kept their clinic appointment with those who did not for
repeat ED visits for 6 months after the study period. Multivariate analysis
evaluated factors associated with keeping appointments. RESULTS: Of 381 patients,
265 (70%) kept their appointments. Show rates did not differ based on age, sex,
race, or language. Patients with commercial insurance were more likely to keep
appointments than Medicare, Medicaid, and uninsured (OR, 51.3; 95% confidence
interval [CI], 2.53-1041.64; P = .010). The 116 no-show patients averaged 0.39
return ED visits (95% CI, 0.15-0.63), and the 265 patients who kept their
appointments averaged 0.28 (95% CI, 0.17-0.39). Two hundred twenty-nine patients
who kept their appointment had no return ED visits, but 36 patients had 74 return
ED visits. There was no difference in return ED visits between the 18 who had
diagnostic cardiac testing (mean, 1.78; 95% CI, 1.60-3.06) and the 18 who did not
(mean, 2.33; 95% CI, 1.20-2.36; P = .251). CONCLUSIONS: This program did not
reduce repeat ED visits. Patients with insurance were more likely to keep follow
up appointments.
PMID- 25124027
TI - Computed tomography scan as a diagnostic tool for supraglottitis in adults.
PMID- 25124029
TI - Effects of familiar contingencies on infants' vocal behavior in new communicative
contexts.
AB - Recently, there has been a growing interest in understanding the mechanisms
underlying vocal learning in songbirds and human infants. Research has
demonstrated how contingent social feedback from social partners to immature
vocalizations can play a role during vocal learning in both brown-headed cowbirds
and prelinguistic infants. Contingencies in social interactions, particularly
familiar contingencies, are important in developing preferences for social
partners and shaping social exchanges Bigelow and Birch [1999]. Infant Behavior &
Development 22:367-382]; however, little is known about how familiar
contingencies that individuals experience during communicative exchanges play a
role in new contexts. The current study examined differences in caregiver
response patterns to infant vocal behavior and assessed how familiar
contingencies influenced infant vocal behavior in novel communicative exchanges
with caregivers. Infants were systematically exposed to high and low social
feedback schedules during a play session. Results revealed the frequency of
caregiver responsiveness to which infants were accustomed to affected infant
vocal production during novel communicative situations. Infants with high
responding caregivers vocalized with more mature vocalizations and used their
vocalizations differently than infants with low responding caregivers during the
high, but not low, response period. Specifically, infants with high responding
caregivers directed more of their vocalizations at their caregiver and looked
more at their caregiver after vocalizing, an indication of anticipating
contingent responding. These results suggest that infants with high responding
caregivers learned the association between vocalizing and contingent responses
during the novel communicative interaction. This study demonstrates the need to
understand how infants who experience a variety of contingencies in everyday
interactions with caregivers carry over to other interactive situations.
PMID- 25124028
TI - Patient factors associated with identification of sepsis in the ED.
PMID- 25124030
TI - The effect of spine postures on the hydrodynamic drag in Epinephelus ongus
larvae.
AB - Laboratory behavioural observation and computational fluid dynamics (CFD)
analysis were conducted to examine whether the movement of the elongated dorsal
and pelvic spines changed the hydrodynamic drag in white-streaked grouper
Epinephelus ongus larvae. The behavioural observation in the tank revealed that
the larvae extended the dorsal and pelvic spines during passive transport and
retracted during swimming; the angles of the dorsal and pelvic spines in relation
to the anteroposterior axis were larger during the passive transport (mean +/-
S.D. = 28.84 +/- 14.27 and 20.35 +/- 15.05 degrees ) than those during the
swimming (mean +/- S.D. = 2.59 +/- 5.55 and 0.32 +/- 6.49 degrees ). The CFD
analysis indicated that the relative hydrodynamic drag acting on the larvae was
approximately 1.25 times higher when the spines were extended (passive transport)
than when the spines were retracted (swimming), suggesting that the E. ongus
larvae have an ability to adjust their hydrodynamic drag depending on the
behavioural context.
PMID- 25124031
TI - Astrocytic inclusions in progressive supranuclear palsy and corticobasal
degeneration.
AB - Tufted astrocytes (TAs) in progressive supranuclear palsy (PSP) and astrocytic
plaques (APs) in corticobasal degeneration (CBD) have been regarded as the
pathological hallmarks of major sporadic 4-repeat tauopathies. To better define
the astrocytic inclusions in PSP and CBD and to outline the pathological features
of each disease, we reviewed 95 PSP cases and 30 CBD cases that were confirmed at
autopsy. TAs exhibit a radial arrangement of thin, long, branching accumulated
tau protein from the cytoplasm to the proximal processes of astrocytes. APs show
a corona-like arrangement of tau aggregates in the distal portions of astrocytic
processes and are composed of fuzzy, short processes. Immunoelectron microscopic
examination using quantum dot nanocrystals revealed filamentous tau accumulation
of APs located in the immediate vicinity of the synaptic structures, which
suggested synaptic dysfunction by APs. The pathological subtypes of PSP and CBD
have been proposed to ensure that the clinical phenotypes are in accordance with
the pathological distribution and degenerative changes. The pathological features
of PSP are divided into 3 representative subtypes: typical PSP type, pallido
nigro-luysian type (PNL type), and CBD-like type. CBD is divided into three
pathological subtypes: typical CBD type, basal ganglia- predominant type, and PSP
like type. TAs are found exclusively in PSP, while APs are exclusive to CBD,
regardless of the pathological subtypes, although some morphological variations
exist, especially with regard to TAs. The overlap of the pathological
distribution of PSP and CBD makes their clinical diagnosis complicated, although
the presence of TAs and APs differentiate these two diseases. The characteristics
of tau accumulation in both neurons and glia suggest a different underlying
mechanism with regard to the sites of tau aggregation and fibril formation
between PSP and CBD: proximal-dominant aggregation of TAs and formation of
filamentous NFTs in PSP in contrast to the distal-dominant aggregation of APs and
formation of less filamentous pretangles in CBD.
PMID- 25124032
TI - Ca2+-mediated mitochondrial reactive oxygen species metabolism augments Wnt/beta
catenin pathway activation to facilitate cell differentiation.
AB - Emerging evidence suggests that reactive oxygen species (ROS) can stimulate the
Wnt/beta-catenin pathway in a number of cellular processes. However, potential
sources of endogenous ROS have not been thoroughly explored. Here, we show that
growth factor depletion in human neural progenitor cells induces ROS production
in mitochondria. Elevated ROS levels augment activation of Wnt/beta-catenin
signaling that regulates neural differentiation. We find that growth factor
depletion stimulates the release of Ca(2+) from the endoplasmic reticulum stores.
Ca(2+) subsequently accumulates in the mitochondria and triggers ROS production.
The inhibition of mitochondrial Ca(2+) uptake with simultaneous growth factor
depletion prevents the rise in ROS metabolism. Moreover, low ROS levels block the
dissociation of the Wnt effector Dishevelled from nucleoredoxin. Attenuation of
the response amplitudes of pathway effectors delays the onset of the Wnt/beta
catenin pathway activation and results in markedly impaired neuronal
differentiation. Our findings reveal Ca(2+)-mediated ROS metabolic cues that fine
tune the efficiency of cell differentiation by modulating the extent of the
Wnt/beta-catenin signaling output.
PMID- 25124033
TI - Degradation of Tiam1 by casein kinase 1 and the SCFbetaTrCP ubiquitin ligase
controls the duration of mTOR-S6K signaling.
AB - Tiam1 (T-cell lymphoma invasion and metastasis 1) is a guanine nucleotide
exchange factor that specifically controls the activity of the small GTPase Rac,
a key regulator of cell adhesion, proliferation, and survival. Here, we report
that in response to mitogens, Tiam1 is degraded by the ubiquitin-proteasome
system via the SCF(betaTrCP) ubiquitin ligase. Mitogenic stimulation triggers the
binding of Tiam1 to the F-box protein betaTrCP via its degron sequence and
subsequent Tiam1 ubiquitylation and proteasomal degradation. The proteolysis of
Tiam1 is prevented by betaTrCP silencing, inhibition of CK1 and MEK, or mutation
of the Tiam1 degron site. Expression of a stable Tiam1 mutant that is unable to
interact with betaTrCP results in sustained activation of the mTOR/S6K signaling
and increased apoptotic cell death. We propose that the SCF(betaTrCP)-mediated
degradation of Tiam1 controls the duration of the mTOR-S6K signaling pathway in
response to mitogenic stimuli.
PMID- 25124034
TI - Interfacial partitioning of a loop hinge residue contributes to diacylglycerol
affinity of conserved region 1 domains.
AB - Conventional and novel isoenzymes of PKC are activated by the membrane-embedded
second messenger diacylglycerol (DAG) through its interactions with the C1
regulatory domain. The affinity of C1 domains to DAG varies considerably among
PKCs. To gain insight into the origin of differential DAG affinities, we
conducted high-resolution NMR studies of C1B domain from PKCdelta (C1Bdelta) and
its W252Y variant. The W252Y mutation was previously shown to render C1Bdelta
less responsive to DAG (Dries, D. R., Gallegos, L. L., and Newton, A. C. (2007) A
single residue in the C1 domain sensitizes novel protein kinase C isoforms to
cellular diacylglycerol production. J. Biol. Chem. 282, 826-830) and thereby
emulate the behavior of C1B domains from conventional PKCs that have a conserved
Tyr at the equivalent position. Our data revealed that W252Y mutation did not
perturb the conformation of C1Bdelta in solution but significantly reduced its
propensity to partition into a membrane-mimicking environment in the absence of
DAG. Using detergent micelles doped with a paramagnetic lipid, we determined that
both the residue identity at position 252 and complexation with diacylglycerol
influence the geometry of C1Bdelta-micelle interactions. In addition, we
identified the C-terminal helix alpha1 of C1Bdelta as an interaction site with
the head groups of phosphatidylserine, a known activator of PKCdelta. Taken
together, our studies (i) reveal the identities of C1Bdelta residues involved in
interactions with membrane-mimicking environment, DAG, and phosphatidylserine, as
well as the affinities associated with each event and (ii) suggest that the
initial ligand-independent membrane recruitment of C1B domains, which is greatly
facilitated by the interfacial partitioning of Trp-252, is responsible, at least
in part, for the differential DAG affinities.
PMID- 25124035
TI - Systematic analysis of bacterial effector-postsynaptic density 95/disc
large/zonula occludens-1 (PDZ) domain interactions demonstrates Shigella OspE
protein promotes protein kinase C activation via PDLIM proteins.
AB - Diseases caused by many Gram-negative bacterial pathogens depend on the
activities of bacterial effector proteins that are delivered into eukaryotic
cells via specialized secretion systems. Effector protein function largely
depends on specific subcellular targeting and specific interactions with cellular
ligands. PDZ domains are common domains that serve to provide specificity in
protein-protein interactions in eukaryotic systems. We show that putative PDZ
binding motifs are significantly enriched among effector proteins delivered into
mammalian cells by certain bacterial pathogens. We use PDZ domain microarrays to
identify candidate interaction partners of the Shigella flexneri effector
proteins OspE1 and OspE2, which contain putative PDZ-binding motifs. We
demonstrate in vitro and in cells that OspE proteins interact with PDLIM7, a
member of the PDLIM family of proteins, which contain a PDZ domain and one or
more LIM domains, protein interaction domains that participate in a wide variety
of functions, including activation of isoforms of protein kinase C (PKC). We
demonstrate that activation of PKC during S. flexneri infection is attenuated in
the absence of PDLIM7 or OspE proteins and that the OspE PDZ-binding motif is
required for wild-type levels of PKC activation. These results are consistent
with a model in which binding of OspE to PDLIM7 during infection regulates the
activity of PKC isoforms that bind to the PDLIM7 LIM domain.
PMID- 25124036
TI - Human trefoil factor 2 is a lectin that binds alpha-GlcNAc-capped mucin glycans
with antibiotic activity against Helicobacter pylori.
AB - Helicobacter pylori infection is the major cause of gastric cancer and remains an
important health care challenge. The trefoil factor peptides are a family of
small highly conserved proteins that are claimed to play essential roles in
cytoprotection and epithelial repair within the gastrointestinal tract. H. pylori
colocalizes with MUC5AC at the gastric surface epithelium, but not with MUC6
secreted in concert with TFF2 by deep gastric glands. Both components of the
gastric gland secretome associate non-covalently and show increased expression
upon H. pylori infection. Although blood group active O-glycans of the Lewis-type
form the basis of H. pylori adhesion to the surface mucin layer and to epithelial
cells, alpha1,4-GlcNAc-capped O-glycans on gastric mucins were proposed to
inhibit H. pylori growth as a natural antibiotic. We show here that the gastric
glycoform of TFF2 is a calcium-independent lectin, which binds with high
specificity to O-linked alpha1,4-GlcNAc-capped hexasaccharides on human and
porcine stomach mucin. The structural assignments of two hexasaccharide isomers
and the binding active glycotope were based on mass spectrometry, linkage
analysis, (1)H nuclear magnetic resonance spectroscopy, glycan inhibition, and
lectin competition of TFF2-mucin binding. Neoglycolipids derived from the C3/C6
linked branches of the two isomers revealed highly specific TFF2 binding to the 6
linked trisaccharide in GlcNAcalpha1-4Galbeta1-4GlcNAcbeta1-6(Fucalpha1-2Galbeta1
3)GalNAc-ol(Structure 1). Supposedly, lectin TFF2 is involved in protection of
gastric epithelia via a functional relationship to defense against H. pylori
launched by antibiotic alpha1,4-GlcNAc-capped mucin glycans. Lectin-carbohydrate
interaction may have also an impact on more general functional aspects of TFF
members by mediating their binding to cell signaling receptors.
PMID- 25124037
TI - Control of Toll-like receptor-mediated T cell-independent type 1 antibody
responses by the inducible nuclear protein IkappaB-zeta.
AB - Antibody responses have been classified as being either T cell-dependent or T
cell-independent (TI). TI antibody responses are further classified as being
either type 1 (TI-1) or type 2 (TI-2), depending on their requirement for B cell
mediated antigen receptor signaling. Although the mechanistic basis of antibody
responses has been studied extensively, it remains unclear whether different
antibody responses share similarities in their transcriptional regulation. Here,
we show that mice deficient in IkappaB-zeta, specifically in their B cells, have
impaired TI-1 antibody responses but normal T cell-dependent and TI-2 antibody
responses. The absence of IkappaB-zeta in B cells also impaired proliferation
triggered by Toll-like receptor (TLR) activation, plasma cell differentiation,
and class switch recombination (CSR). Mechanistically, IkappaB-zeta-deficient B
cells could not induce TLR-mediated induction of activation-induced cytidine
deaminase (AID), a class-switch DNA recombinase. Retroviral transduction of AID
in IkappaB-zeta-deficient B cells restored CSR activity. Furthermore, acetylation
of histone H3 in the vicinity of the transcription start site of the gene that
encodes AID was reduced in IkappaB-zeta-deficient B cells relative to IkappaB
zeta-expressing B cells. These results indicate that IkappaB-zeta regulates TLR
mediated CSR by inducing AID. Moreover, IkappaB-zeta defines differences in the
transcriptional regulation of different antibody responses.
PMID- 25124038
TI - Biochemical characterization of mutants in chaperonin proteins CCT4 and CCT5
associated with hereditary sensory neuropathy.
AB - Hereditary sensory neuropathies are a class of disorders marked by degeneration
of the nerve fibers in the sensory periphery neurons. Recently, two mutations
were identified in the subunits of the eukaryotic cytosolic chaperonin TRiC, a
protein machine responsible for folding actin and tubulin in the cell. C450Y CCT4
was identified in a stock of Sprague-Dawley rats, whereas H147R CCT5 was found in
a human Moroccan family. As with many genetically identified mutations associated
with neuropathies, the underlying molecular basis of the mutants was not defined.
We investigated the biochemical properties of these mutants using an expression
system in Escherichia coli that produces homo-oligomeric rings of CCT4 and CCT5.
Full-length versions of both mutant protein chains were expressed in E. coli at
levels approaching that of the WT chains. Sucrose gradient centrifugation
revealed chaperonin-sized complexes of both WT and mutant chaperonins, but with
reduced recovery of C450Y CCT4 soluble subunits. Electron microscopy of
negatively stained samples of C450Y CCT4 revealed few ring-shaped species,
whereas WT CCT4, H147R CCT5, and WT CCT5 revealed similar ring structures. CCT5
complexes were assayed for their ability to suppress aggregation of and refold
the model substrate gammad-crystallin, suppress aggregation of mutant huntingtin,
and refold the physiological substrate beta-actin in vitro. H147R CCT5 was not as
efficient in chaperoning these substrates as WT CCT5. The subtle effects of these
mutations are consistent with the homozygous disease phenotype, in which most
functions are carried out during development and adulthood, but some selective
function is lost or reduced.
PMID- 25124039
TI - The mitochondrial ADP/ATP carrier associates with the inner membrane presequence
translocase in a stoichiometric manner.
AB - The majority of mitochondrial proteins are synthesized with amino-terminal signal
sequences. The presequence translocase of the inner membrane (TIM23 complex)
mediates the import of these preproteins. The essential TIM23 core complex
closely cooperates with partner protein complexes like the presequence
translocase-associated import motor and the respiratory chain. The inner
mitochondrial membrane also contains a large number of metabolite carriers, but
their association with preprotein translocases has been controversial. We
performed a comprehensive analysis of the TIM23 interactome based on stable
isotope labeling with amino acids in cell culture. Subsequent biochemical studies
on identified partner proteins showed that the mitochondrial ADP/ATP carrier
associates with the membrane-embedded core of the TIM23 complex in a
stoichiometric manner, revealing an unexpected connection of mitochondrial
protein biogenesis to metabolite transport. Our data indicate that direct TIM23
AAC coupling may support preprotein import into mitochondria when respiratory
activity is low.
PMID- 25124040
TI - Biosynthesis and translocation of unsulfated acyltrehaloses in Mycobacterium
tuberculosis.
AB - A number of species-specific polymethyl-branched fatty acid-containing trehalose
esters populate the outer membrane of Mycobacterium tuberculosis. Among them, 2,3
diacyltrehaloses (DAT) and penta-acyltrehaloses (PAT) not only play a structural
role in the cell envelope but also contribute to the ability of M. tuberculosis
to multiply and persist in the infected host, promoting the intracellular
survival of the bacterium and modulating host immune responses. The nature of the
machinery, topology, and sequential order of the reactions leading to the
biosynthesis, assembly, and export of these complex glycolipids to the cell
surface are the object of the present study. Our genetic and biochemical evidence
corroborates a model wherein the biosynthesis and translocation of DAT and PAT to
the periplasmic space are coupled and topologically split across the plasma
membrane. The formation of DAT occurs on the cytosolic face of the plasma
membrane through the action of PapA3, FadD21, and Pks3/4; that of PAT occurs on
the periplasmic face via transesterification reactions between DAT substrates
catalyzed by the acyltransferase Chp2 (Rv1184c). The integral membrane
transporter MmpL10 is essential for DAT to reach the cell surface, and its
presence in the membrane is required for Chp2 to be active. Disruption of mmpL10
or chp2 leads to an important build-up of DAT inside the cells and to the
formation of a novel form of unsulfated acyltrehalose esterified with polymethyl
branched fatty acids normally found in sulfolipids that is translocated to the
cell surface.
PMID- 25124041
TI - Allosteric regulation of a protein acetyltransferase in Micromonospora aurantiaca
by the amino acids cysteine and arginine.
AB - ACT domains (amino acid-binding domains) are linked to a wide range of metabolic
enzymes that are regulated by amino acid concentration. Seventy proteins with ACT
GCN5-related N-acetyltransferase (GNAT) domain organization were found in
actinomycetales. In this study, we investigate the ACT-containing GNAT
acetyltransferase, Micau_1670 (MaKat), from Micromonospora aurantiaca ATCC 27029.
Arginine and cysteine were identified as ligands by monitoring the conformational
changes that occur upon amino acids binding to the ACT domain in the MaKat
protein using FRET assay. It was found that MaKat is an amino acid-regulated
protein acetyltransferase, whereas arginine and cysteine stimulated the activity
of MaKat with regard to acetylation of acetyl-CoA synthetase (Micau_0428). Our
research reveals the biochemical characterization of a protein acetyltransferase
that contains a fusion of a GNAT domain with an ACT domain and provides a novel
signaling pathway for regulating cellular protein acetylation. These findings
indicate that acetylation of proteins and acetyltransferase activity may be
tightly linked to cellular concentrations of some amino acids in actinomycetales.
PMID- 25124042
TI - Crystal structure of the ubiquitin-like domain-CUT repeat-like tandem of special
AT-rich sequence binding protein 1 (SATB1) reveals a coordinating DNA-binding
mechanism.
AB - SATB1 is essential for T-cell development and growth and metastasis of multitype
tumors and acts as a global chromatin organizer and gene expression regulator.
The DNA binding ability of SATB1 plays vital roles in its various biological
functions. We report the crystal structure of the N-terminal module of SATB1.
Interestingly, this module contains a ubiquitin-like domain (ULD) and a CUT
repeat-like (CUTL) domain (ULD-CUTL tandem). Detailed biochemical experiments
indicate that the N terminus of SATB1 (residues 1-248, SATB1((1-248))), including
the extreme 70 N-terminal amino acids, and the ULD-CUTL tandem bind specifically
to DNA targets. Our results show that the DNA binding ability of full-length
SATB1 requires the contribution of the CUTL domain, as well as the CUT1-CUT2
tandem domain and the homeodomain. These findings may reveal a multiple-domain
coordinated mechanism whereby SATB1 recognizes DNA targets.
PMID- 25124044
TI - Newborn screening for pompe disease? a qualitative study exploring professional
views.
AB - BACKGROUND: Developments in enzyme replacement therapy have kindled discussions
on adding Pompe disease, characterized by progressive muscle weakness and
wasting, to neonatal screening. Pompe disease does not fit traditional screening
criteria as it is a broad-spectrum phenotype disorder that may occur in lethal
form in early infancy or manifest in less severe forms from infancy to late
adulthood. Current screening tests cannot differentiate between these forms.
Normally, expanding screening is discussed among experts in advisory bodies.
While advisory reports usually mention the procedures and outcome of
deliberations, little is known of the importance attached to different arguments
and the actual weighing processes involved. In this research we aim to explore
the views of a wide range of relevant professionals to gain more insight into the
process of weighing pros and cons of neonatal screening for Pompe disease, as an
example of the dilemmas involved in screening for broad-spectrum phenotype
disorders. METHODS: We conducted 24 semi-structured interviews with medical, lab,
insurance and screening professionals, and executive staff of patient
organisations. They were asked about their first reaction to neonatal screening
for Pompe disease, after which benefits and harms and requirements for screening
were explored in more detail. RESULTS: Advantages included health gain by timely
intervention, avoiding a diagnostic quest, having a reproductive choice and
gaining more knowledge about the natural course and treatment. Being prepared was
mentioned as an advantage for the later manifesting cases. Disadvantages included
treatment costs and uncertainties about its effect, the timing of treatment in
later manifesting cases, the psychological burden for the patient-in-waiting and
the family. Also the downsides of having prior knowledge as well as having to
consider a reproductive option were mentioned as disadvantages. CONCLUSION: When
weighing pros and cons, interviewees attach different importance to different
arguments, based on personal and professional views. Professionals expect
benefits from neonatal screening for Pompe disease, especially for early-onset
cases. Some interviewees valued screening in later manifesting cases as well,
while stressing the need for adequate support of pre-symptomatic patients and
their families. Others considered the psychological burden and uncertainties
regarding treatment as reasons not to screen.
PMID- 25124043
TI - Shutdown of achaete-scute homolog-1 expression by heterogeneous nuclear
ribonucleoprotein (hnRNP)-A2/B1 in hypoxia.
AB - The basic helix-loop-helix transcription factor hASH1, encoded by the ASCL1 gene,
plays an important role in neurogenesis and tumor development. Recent findings
indicate that local oxygen tension is a critical determinant for the progression
of neuroblastomas. Here we investigated the molecular mechanisms underlying the
oxygen-dependent expression of hASH1 in neuroblastoma cells. Exposure of human
neuroblastoma-derived Kelly cells to 1% O2 significantly decreased ASCL1 mRNA and
hASH1 protein levels. Using reporter gene assays, we show that the response of
hASH1 to hypoxia is mediated mainly by post-transcriptional inhibition via the
ASCL1 mRNA 5'- and 3'-UTRs, whereas additional inhibition of the ASCL1 promoter
was observed under prolonged hypoxia. By RNA pulldown experiments followed by
MALDI/TOF-MS analysis, we identified heterogeneous nuclear ribonucleoprotein
(hnRNP)-A2/B1 and hnRNP-R as interactors binding directly to the ASCL1 mRNA 5'-
and 3'-UTRs and influencing its expression. We further demonstrate that hnRNP
A2/B1 is a key positive regulator of ASCL1, findings that were also confirmed by
analysis of a large compilation of gene expression data. Our data suggest that a
prominent down-regulation of hnRNP-A2/B1 during hypoxia is associated with the
post-transcriptional suppression of hASH1 synthesis. This novel post
transcriptional mechanism for regulating hASH1 levels will have important
implications in neural cell fate development and disease.
PMID- 25124045
TI - Prospective study of ultrasound-guided percutaneous renal cryotherapy: case
selection as an optimization factor for a technique.
AB - OBJECTIVE: To evaluate the technical and oncological effectiveness of ultrasound
guided percutaneous renal cryotherapy (PRC) in a selected group of patients with
renal cancer. MATERIAL AND METHODS: We conducted a prospective study of 28
patients with posterior-facing T1a renal tumors with middle and inferior external
borders. All patients underwent ultrasound-guided PRC. Follow-up was conducted
with computed tomography at 1 month and then every 6 months, with a good result
defined as the total absence of contrast incorporation. We performed a
descriptive and survival study using the Kaplan-Meier estimator. RESULTS: The 28
patients had a mean age (SD) of 68.3 (10.1) years, and the group underwent 28
procedures. The mean (SD) size of the tumors was 25.5 (7.5) mm, the mean
nephrometry score was 1.41 (0.52) and the mean preoperative creatinine level was
133.5 (144.1) mmol/L. There were no intraoperative complications. In terms of
postoperative complications, there was only 1 case (3.5%) of a skin lesion
resulting from treating a tumor in a transplanted kidney (Clavien II). The median
follow-up was 25 months, and the mean (SD) postoperative creatinine level was
135.5 (110.3) mmol/L. Two cases presented radiological recurrence (93% efficacy),
with a mean time to recurrence of 12 and 19 months, respectively. There were no
tumor-related deaths. CONCLUSIONS: Our series (the largest on PRC in our country
to date) shows that, with an appropriate selection of tumors, PRC is a safe
technique with minimal morbidity. Ultrasonography enables the controlled
performance of the procedure and saves the patient from radiation and reduces
costs.
PMID- 25124046
TI - Opisthorchis viverrini: analysis of the sperm-specific rhophilin associated tail
protein 1-like.
AB - Concurrent deficiency of rhophilin associated tail protein (ROPN1) and ROPN1-like
(ROPN1L) in mice causes structural abnormalities and immotility of sperm and
thereby infertility. In the present research, ROPN1L of the human liver fluke
Opisthorchis viverrini was molecularly characterized and showed unexpected
potential as a diagnostic tool. ROPN1L transcripts were detected in 2-week-old
juveniles by RT-PCR. Immunohistochemical analysis of the adult worm localized the
protein in testis lobes, seminal vesicle and receptacle and immunoelectron
microscopic analysis revealed its location on the tail of spermatozoa.
Interestingly, sera of experimentally infected hamsters and sera of individuals
suffering from opisthorchiasis showed reactivity to recombinant OvROPN1L
(rOvROPN1L). The protein shows modest conservation to the human homolog at 47.2%
sequence identity and a mouse anti-rOvROPN1L antiserum was not reactive with
sperm protein extracts from hamsters, mice and rats. Unsurprisingly, conservation
is higher in trematodes, e.g. 78.4% and 71.2% identity to Fasciola gigantica and
Schistosoma haematobium, respectively and evaluation of diagnostic specificity is
required using sera of individuals suffering from different trematodiases in
Thailand.
PMID- 25124048
TI - A-site sub-stoichiometry and oxygen vacancies as the origin of the electrical
properties of Sr2-yLuNb1-xTixO6-delta perovskite-like materials.
AB - Aliovalent substitution of Nb(5+) by Ti(4+) in Sr2LuNbO6 is limited to 10% of Nb
atoms. A full structural determination by NPD confirms this and reveals that the
structure is better described as a superstructure of the simple cubic perovskite
(as previously reported) with the monoclinic cell 2(1/2)ap* 2(1/2)ap* 2ap and
beta~ 90 degrees (S.G. P21/n). The substituted materials present both oxygen
vacancies induced by charge compensation and Sr-deficiency. Therefore, their
formula should be given as Sr2-yLuNb1-xTixO6-delta. Electrical properties can be
fully understood considering these compositional defects. The parent compound
Sr2LuNbO6 presents low electrical conductivity in air, which improves by more
than one order of magnitude upon Ti substitution. In any case, the title oxides
show low electrical conductivity in a wide oxygen partial pressure (pO2) range
(10(-25) atm <=pO2<= 10(-1) atm). At high pO2 the conductivity increases with pO2
due to oxygen-vacancy annihilation and hole creation, according to a general p
type semiconducting mechanism; A-site substoichiometry and Ti-substitution are
the origin of this behaviour. In the low pO2 region, the conductivity increases
as the oxygen partial pressure decreases. Reduction of cations, Nb(5+) or Ti(4+),
supports n-type conduction by electrons and oxygen vacancy creation. For the
intermediate pO2 range a low ionic conduction contribution is observed. Although
the estimated ionic conductivity is not high in the substituted compounds, the
strategy seems to be valid since a significant enhancement of ionic conduction is
observed upon aliovalent substitution.
PMID- 25124047
TI - A meta-analysis of external fixator versus intramedullary nails for open tibial
fracture fixation.
AB - BACKGROUND: To compare the clinical outcomes of external fixator (EF) and
intramedullary nails (IN) in the treatment of open tibial fractures. METHODS: We
searched seven electronic databases (PubMed, MEDLINE, EMBASE, OVID, Cochrane
library, CNKI, and CBM) for trials of tibial fracture fixation published from
1980 to 2013. The indicators including postoperative infection, malunion,
nonunion, soft tissue injury, delayed healing, and healing time were used for
quantitative outcome assessments. RESULTS: A total of nine trials involving 532
patients (EF, n = 253; IN, n = 279) with open tibia fractures were included in
this meta-analysis. The results indicated that the patients undergoing IN had
lower incidence of postoperative infection (risk radio [RR] = 3.85; 95%
confidence intervals [CI], 2.67-5.54; P < 0.0001), malunion (RR = 2.31; 95% CI,
1.40-3.81; P = 0.001), nonunion (RR = 1.41; 95% CI, 1.06-1.88; P = 0.02) and less
healing time (weighted mean difference [WMD] = 6.19; 95% CI, 1.42-10.96; P =
0.01) compared with EF. However, regarding to the soft tissue injury (RR = 0.74;
95% CI, 0.34-1.62; P = 0.45) and delayed healing (RR = 1.38; 95% CI, 0.79-2.43; P
= 0.26), there is no significantly difference between EF and IN approach.
CONCLUSION: In conclusion, the use of IN is more effective than EF and may be
considered as first-line approach in fixation of open tibial fractures.
PMID- 25124049
TI - The solid-state continuum: a perspective on the interrelationships between
different solid-state forms in drug substance and drug product.
AB - OBJECTIVE: The objective of the review is to provide an overview of the
nomenclature used in the solid-state continuum and relate these to the
development of drug substances and drug products. KEY FINDINGS: The importance of
a rational approach to solid-state form selection, including integrated decision
making (ensuring equal weight is given to the needs of the drug substance and the
drug product), is vital for the effective development of a drug candidate. For
example, how do secondary processing considerations influence the selection of
drug substance solid-state form and resulting formulation, and how can drug
substance solid-state form be used to optimise secondary processing? Further, the
potential use of 'crystal' engineering to optimise stability, purity and optical
resolutions, and the linked regulatory requirements, will be discussed. SUMMARY:
The nomenclature used in the solid-state continuum, which contains a large number
of different crystalline and non-crystalline forms, for example, amorphous
systems, was reviewed. Further, the significant role of the drug substance within
the solid oral dose form from a physicochemical perspective was covered.
PMID- 25124050
TI - Childhood trauma and eating psychopathology: a mediating role for dissociation
and emotion dysregulation?
AB - The present study examined the relationship between different forms of childhood
trauma and eating psychopathology using a multiple mediation model that included
emotion dysregulation and dissociation as hypothesised mediators. 142 female
undergraduate psychology students studying at two British Universities
participated in this cross-sectional study. Participants completed measures of
childhood trauma (emotional abuse, physical abuse, sexual abuse, emotional
neglect and physical neglect), eating psychopathology, dissociation and emotion
dysregulation. Multiple mediation analysis was conducted to investigate the
study's proposed model. Results revealed that the multiple mediation model
significantly predicted eating psychopathology. Additionally, both emotion
dysregulation and dissociation were found to be significant mediators between
childhood trauma and eating psychopathology. A specific indirect effect was
observed between childhood emotional abuse and eating psychopathology through
emotion dysregulation. Findings support previous research linking childhood
trauma to eating psychopathology. They indicate that multiple forms of childhood
trauma should be assessed for individuals with eating disorders. The possible
maintaining role of emotion regulation processes should also be considered in the
treatment of eating disorders.
PMID- 25124051
TI - Exploring policies for the reduction of child physical abuse and neglect.
AB - Policies can be powerful tools for prevention given their potential to affect
conditions that can improve population-level health. Given the dearth of
empirical research on policies' impacts on child maltreatment, this article (a)
identifies 37 state policies that might have impacts on the social determinants
of child maltreatment; (b) identifies available data sources documenting the
implementation of 31 policies; and (c) utilizes the available data to explore
effects of 11 policies (selected because they had little missing data) on child
maltreatment rates. These include two policies aimed at reducing poverty, two
temporary assistance to needy families policies, two policies aimed at increasing
access to child care, three policies aimed at increasing access to high quality
pre-K, and three policies aimed at increasing access to health care. Multi-level
regression analyses between within-state trends of child maltreatment
investigation rates and these 11 policies, controlling for states' childhood
poverty, adults without a high school diploma, unemployment, child burden, and
race/ethnicity, identified two that were significantly associated with decreased
child maltreatment rates: lack of waitlists to access subsidized child care and
policies that facilitate continuity of child health care. These findings are
correlational and are limited by the quality and availability of the data. Future
research might focus on a reduced number of states that have good quality
administrative data or population-based survey data on child maltreatment or
reasonable proxies for child maltreatment and where data on the actual
implementation of specific policies of interest can be documented.
PMID- 25124052
TI - Computed tomographic findings in 15 dogs with eosinophilic bronchopneumopathy.
AB - Eosinophilic bronchopneumopathy is a disease characterized by the infiltration of
the lung and bronchial mucosa by eosinophils. The aim of the present study was to
describe the CT findings in a large series of dogs with confirmed diagnosis of
eosinophilic bronchopneumopathy. Computed tomographic scans of 15 dogs with
confirmed diagnosis of eosinophilic bronchopneumopathy were evaluated
retrospectively by two boarded radiologists who reached a consensus.
Abnormalities were identified in 14/15 (93%) dogs, including pulmonary
parenchymal abnormalities in 14/15 (93%) dogs, bronchial wall thickening in 13
(87%) dogs, which was considered marked in eight (53%), plugging of the bronchial
lumen by mucus/debris in 11 (73%) dogs, and bronchiectasis in nine (60%) dogs.
Pulmonary nodules were identified in 5/15 (33%) dogs including one dog with a
mass. All dogs with a nodular lung pattern had additional abnormalities.
Lymphadenopathy was present in 10 dogs (67%). Lesions associated with
eosinophilic bronchopneumopathy are variable and heterogeneous and encompass a
wider variety of computed tomographic features than reported previously. Computed
tomographic images were abnormal in the majority of affected dogs, hence CT is a
useful modality to characterize the nature and distribution of thoracic lesions
in dogs with eosinophilic bronchopneumopathy.
PMID- 25124053
TI - VMAT2 and Parkinson's disease: old dog, new tricks.
PMID- 25124055
TI - Cytostatic drugs and metabolites in municipal and hospital wastewaters in Spain:
filtration, occurrence, and environmental risk.
AB - Concerns about cytostatic anticancer drugs in the environment are increasing,
mainly due to the lack of knowledge about the fate and impact of these cytotoxic
compounds in the water cycle. In this context, the present work investigated the
occurrence of 13 cytostatics and 4 metabolites in wastewater samples from various
wastewater treatment plants (WWTPs) and from a large hospital from Spain. The
target compounds belong to five different classes according to the Anatomical
Therapeutic Classification (ATC), namely, alkylating agents, antimetabolites,
plant alkaloids and other natural products, cytotoxic antibiotics and related
substances, and other antineoplastic agents. Some of them have been classified as
carcinogens in humans by the International Agency for Research on Cancer (IARC).
These compounds were determined by an automated on line solid-phase extraction
liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) method. Results
showed the presence of methotrexate (MET), ifosfamide (IF), cyclophosphamide
(CP), irinotecan (IRI), doxorubicin (DOX), capecitabine (CAP), tamoxifen (TAM)
and the metabolites endoxifen (OH-D-TAM), hydroxytamoxifen (OH-TAM) and
hydroxypaclitaxel (OH-PAC) at levels ranging from 2 ng L(-1) (for MET) to 180 ng
L(-1) (for TAM). Some of these compounds were found to be efficiently removed
after wastewater treatment, e.g. MET, DOX and IRI, whereas other compounds, such
as TAM, CP and IF remained largely unaltered. The behaviour of the target
compounds during the common filtration step of the water samples was also
investigated with the finding that some compounds are strongly adsorbed to nylon
filters, while cellulose acetate appears as the best choice for the filter
material. The aquatic environmental risk associated to the detected compounds was
also assessed. To the best of the authors' knowledge, this is the first report of
the presence of the metabolites OH-D-TAM and OH-TAM in the water cycle.
PMID- 25124054
TI - Correlation between optical coherence tomography-derived intraluminal parameters
and fractional flow reserve measurements in intermediate grade coronary lesions:
a comparison between diabetic and non-diabetic patients.
AB - BACKGROUND: Fractional flow reserve (FFR) measurements accurately assess
functional relevance in intermediate grade coronary lesions. A significant
relationship between hemodynamic stenosis severity and optical coherence
tomography (OCT)-derived intraluminal dimensions has recently been demonstrated.
However, morphologic thresholds to identify significant stenoses are variable and
exploration of this correlation in patients with diabetes mellitus (DM) remains
currently incomplete. This study aimed at comparing the diagnostic value of
intraluminal parameters as determined by OCT to predict FFR <=0.8 in lesions of
patients with versus without DM. METHODS: In 100 patients (DM = 56, non-DM = 44)
with 142 coronary de novo lesions (DM = 80, non-DM = 62) of intermediate grade as
determined by quantitative coronary angiography, we performed OCT and FFR.
Stenoses were defined functionally relevant if FFR was <=0.8. RESULTS: FFR
measurements in the overall study cohort, the DM and the non-DM group correlated
significantly with minimal lumen area (MLA) [overall: r (2) = 0.339, DM: r (2) =
0.341, non-DM: r (2) = 0.355 (all p < 0.001)], percent area stenosis [overall: r
(2) = 0.352, DM: r (2) = 0.376, non-DM: r (2) = 0.351 (all p < 0.001)] and
minimal lumen diameter [overall: r (2) = 0.333, DM: r (2) = 0.277, non-DM: r (2)
= 0.417 (all p < 0.001)] without differing statistically between diabetic and non
diabetic patients (p = ns). Receiver operating characteristic analysis
demonstrated that among OCT-derived parameters, MLA predicted FFR <=0.8 with the
best diagnostic efficiency and with similar cut-off values for all patients [area
under the curve (AUC) = 0.836, 95% confidence interval (CI) = 0.772-0.901, cut
off value = 1.64 mm(2)] as well as for diabetic (AUC = 0.840, 95% CI = 0.754
0.927, cut-off value = 1.59 mm(2)) and non-diabetic subjects (AUC = 0.833, 95% CI
= 0.734-0.932, cut-off value = 1.64 mm(2)). CONCLUSION: In both, diabetic and non
diabetic patients, FFR and OCT-derived intraluminal measurements are
significantly correlated and OCT predicts hemodynamically relevant coronary
stenosis with moderate diagnostic efficiency.
PMID- 25124056
TI - Effects of nano-ZnO on the agronomically relevant Rhizobium-legume symbiosis.
AB - The impact of nano-ZnO (nZnO) on Rhizobium-legume symbiosis was studied with
garden pea and its compatible bacterial partner Rhizobium leguminosarum bv.
viciae 3841. Exposure of peas to nZnO had no impact on germination, but
significantly affected root length. Chronic exposure of plant to nZnO impacted
its development by decreasing the number of the first- and the second-order
lateral roots, stem length, leaf surface area, and transpiration. The effect of
nZnO dissolution on phytotoxicity was also examined. Results showed that Zn(2+)
had negative impact on plant development. Exposure of R. leguminosarum bv. viciae
3841 to nZnO brought about morphological changes by rendering the microbial cells
toward round shape and damaging the bacterial surface. Furthermore, the presence
of nZnO in the rhizosphere affected root nodulation, delayed the onset of
nitrogen fixation, and caused early senescence of nodules. Attachment of
nanoparticles on the root surface and dissolution of Zn(2+) are important factors
affecting the phytotocity of nZnO. Hence, the presence of nZnO in the environment
is potentially hazardous to the Rhizobium-legume symbiosis system.
PMID- 25124057
TI - Foster care, externalizing disorders, and antipsychotic use among Medicaid
enrolled youths.
AB - OBJECTIVES: The authors investigated the extent to which clinical diagnoses of
externalizing disorders explain higher rates of antipsychotic use by foster care
youths. METHODS: Medicaid claims data from 44 states for 2009 for youths in
foster care (N=301,894) and those not in foster care (N=5,092,574) were analyzed,
excluding those with schizophrenia, bipolar disorder, autism, and major
depressive disorder. Logistic regressions assessed the relationship between
foster care, externalizing disorders, and antipsychotic use. RESULTS: Foster care
youths had higher rates of externalizing disorders than the comparison group
(attention-deficit hyperactivity disorder, 17.3% versus 6.5%; disruptive behavior
disorder, 7.2% versus 2.5%; conduct disorder, 2.3% versus .5%) and greater
antipsychotic use (7.4% versus 1.4%). Foster care remained a significant
predictor of antipsychotic use after control for demographic and diagnostic
covariates, including externalizing disorders (adjusted odds ratio=2.59, 95%
confidence interval=2.54-2.63). CONCLUSIONS: High rates of externalizing disorder
diagnoses only partially explained elevated levels of antipsychotic use in this
vulnerable population.
PMID- 25124058
TI - Granulation of increasingly hydrophobic formulations using a twin screw
granulator.
AB - The application of twin screw granulation in the pharmaceutical industry has
generated increasing interest due to its suitability for continuous processing.
However, an understanding of the impact of formulation properties such as
hydrophobicity on intermediate and finished product quality has not yet been
established. Hence, the current work investigated the granulation behaviour of
three formulations containing increasing amounts of hydrophobic components using
a ConsigmaTM-1 twin screw granulator. Process conditions including powder feed
rate, liquid to solid ratio, granulation liquid composition and screw
configuration were also evaluated. The size of the wet granules was measured in
order to enable exploration of granulation behaviour in isolation without
confounding effects from downstream processes such as drying. The experimental
observations indicated that the granulation process was not sensitive to the
powder feed rate. The hydrophobicity led to heterogeneous liquid distribution and
hence a relatively large proportion of un-wetted particles. Increasing numbers of
kneading elements led to high shear and prolonged residence time, which acted to
enhance the distribution of liquid and feeding materials. The bimodal size
distributions considered to be characteristic of twin screw granulation were
primarily ascribed to the breakage of relatively large granules by the kneading
elements.
PMID- 25124059
TI - Amphiphilic chitosan-grafted-functionalized polylactic acid based nanoparticles
as a delivery system for doxorubicin and temozolomide co-therapy.
AB - The aim of this work was to investigate the potential of an amphiphilic system
comprising chitosan-grafted polylactide and carboxyl-functionalized polylactide
acid as a carrier for the controlled release and co-release of two DNA alkylating
drugs: doxorubicin and temozolomide. Polylactide and carboxyl-functionalized
polylactide acid were obtained through direct melt polycondensation reaction,
using methanesulfonic acid as a non-toxic initiator, and subsequently these were
grafted to the chitosan backbone through a coupling reaction, utilizing 1-ethyl-3
(3-dimethylaminopropyl) carbodiimide as a condensing agent. ATR-FTIR analysis and
conductometric titration confirmed that a reaction between CS and PLA, PLACA2%
and PLACA5% occurred. Chitosan-grafted-polylactide and polylactide-citric acid
nanoparticles were prepared via the polyelectrolyte complex technique, applying
dextran sulphate as a polyanion, and loaded with doxorubicin and temozolomide.
The diameter of particles, zeta-potential and their relationship to temperature
and pH were analysed in all formulations. Encapsulation, co-encapsulation
efficiency and release studies were conducted in different physiological
simulated environments and human serum. Results showed the continuous release of
drugs without an initial burst in different physiological media.
PMID- 25124060
TI - Test performance of PET-CT for mediastinal lymph node staging of pulmonary
carcinoid tumours.
AB - Positron emission tomography-CT (PET-CT) is one of the initial mediastinal
staging modality for non-small cell lung cancer; however, the clinical utility in
carcinoid tumours is uncertain. We sought to determine the test performance of
PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumours. We
collated data from seven institutions, performing a retrospective search on
pathological databases for a consecutive series of patients who underwent
thoracic surgery (with lymph nodal dissection) for carcinoid tumours with
preoperative PET-CT staging. PET-CT results were compared with the reference
standard of pathologic results obtained from lymph node dissection and test
performance reported using sensitivity and specificity. From November 1999 to
January 2013, 247 patients from seven institutions underwent surgery for
carcinoid tumours with a corresponding preoperative PET-CT scan. The mean age of
the patients was 61 (SD 15, range 73) and 84 were male patients (34%). The
pathologic subtype was typical carcinoid in 217 patients (88%) and atypical
carcinoid in 30 patients (12%). Results from lymph node dissection were obtained
in 207 patients. The calculated sensitivity and specificity of PET-CT to identify
mediastinal lymph node disease was 33% (95% CI 4% to 78%) and 94% (95% CI 89% to
97%), respectively. Our results indicate that PET-CT has a poor sensitivity but
good specificity to detect the presence of mediastinal lymph node metastases in
pulmonary carcinoid tumours. Mediastinal lymph node metastases cannot be ruled
out with negative PET-CT uptake, and if the absence of mediastinal lymph node
disease is a prerequisite for directing management, tissue sampling should be
undertaken.
PMID- 25124063
TI - An unusual stacking transformation in liquid-crystalline columnar assemblies of
clicked molecular propellers with tunable light emissions.
AB - The columnar liquid-crystalline (LC) and fluorescence properties of three
dimensional molecular propellers based on tetraphenylethylene is reported. X-ray
scattering studies reveal an unusual transition from a rectangular (Colrec ) to a
hexagonal columnar (Colhex ) phase. In contrast to second-order intercolumnar
transitions based on a common tilt mechanism, the transition is first order and
involves an unprecedented zigzag stacking of aromatic propellers in the Colrec
phase. A sudden change in emission color from sky blue to green occurs rapidly
and reversibly at this transition, which is due to the planarization of the
propeller mesogen.
PMID- 25124061
TI - Prevention of infections during primary immunodeficiency.
AB - Because infectious diseases are a major source of morbidity and mortality in the
majority of patients with primary immunodeficiencies (PIDs), the application of a
prophylactic regimen is often necessary. However, because of the variety of PIDs
and pathogens involved, and because evidence is scarce, practices are
heterogeneous. To homogenize practices among centers, the French National
Reference Center for PIDs aimed at elaborating recommendations for anti
infectious prophylaxis for the most common PIDs. We performed a literature review
of infectious complications and prophylactic regimens associated with the most
frequent PIDs. Then, a working group including different specialists
systematically debated about chemoprophylaxis, immunotherapy, immunization, and
recommendations for patients. Grading of prophylaxis was done using strength of
recommendations (decreasing from A to D) and evidence level (decreasing from I to
III). These might help infectious diseases specialists in the management of PIDs
and improving the outcome of patients with PIDs.
PMID- 25124064
TI - The impact of genetic heterogeneity on biomarker development in kidney cancer
assessed by multiregional sampling.
AB - Primary clear cell renal cell carcinoma (ccRCC) genetic heterogeneity may lead to
an underestimation of the mutational burden detected from a single site
evaluation. We sought to characterize the extent of clonal branching involving
key tumor suppressor mutations in primary ccRCC and determine if genetic
heterogeneity could limit the mutation profiling from a single region assessment.
Ex vivo core needle biopsies were obtained from three to five different regions
of resected renal tumors at a single institution from 2012 to 2013. DNA was
extracted and targeted sequencing was performed on five genes associated with
ccRCC (von-Hippel Lindau [VHL], PBRM1, SETD2, BAP1, and KDM5C). We constructed
phylogenetic trees by inferring clonal evolution based on the mutations present
within each core and estimated the predictive power of detecting a mutation for
each successive tumor region sampled. We obtained 47 ex vivo biopsy cores from 14
primary ccRCC's (median tumor size 4.5 cm, IQR 4.0-5.9 cm). Branching patterns of
various complexities were observed in tumors with three or more mutations. A VHL
mutation was detected in nine tumors (64%), each time being present ubiquitously
throughout the tumor. Other genes had various degrees of regional mutational
variation. Based on the mutations' prevalence we estimated that three different
tumor regions should be sampled to detect mutations in PBRM1, SETD2, BAP1, and/or
KDM5C with 90% certainty. The mutational burden of renal tumors varies by region
sampled. Single site assessment of key tumor suppressor mutations in primary
ccRCC may not adequately capture the genetic predictors of tumor behavior.
PMID- 25124066
TI - Targeted genome regulation and modification using transcription activator-like
effectors.
AB - Transcription activator-like effectors (TALEs) are immensely powerful new tools
for genome engineering that can be directed to bind to almost any DNA sequence of
choice. They originate from the Xanthomonas species of plant pathogenic bacteria
and, in nature, these proteins increase the virulence of Xanthomonas. However, in
2009, the DNA binding code of TALEs was deciphered and, subsequently, TALE
proteins have been exploited for many diverse applications. Custom TALEs that
target almost any required DNA sequence can be readily constructed in < 1 week.
One major application is gene editing: TALEs fused with the Fok I endonuclease
catalytic domain can induce double-stranded breaks at a chosen genomic location,
similar to zinc finger nucleases. Designer TALE transcription factors have also
been developed by linking TALEs to a transcription AD, such as VP64. More
recently, TALEs have been developed that can repress transcription, bind
methylated DNA or act as fluorescent chromatin probes. In the present review, we
describe the assembly of designer TALEs, their expanding range of current and
potential future applications, and briefly discuss alternatives, namely, zinc
finger nucleases and clustered regularly interspaced short palindromic
repeat/clustered regularly interspaced short palindromic repeat associated
protein 9.
PMID- 25124065
TI - Novel GALT variations and mutation spectrum in the Korean population with
decreased galactose-1-phosphate uridyltransferase activity.
AB - BACKGROUND: Classic galactosemia (OMIM #230400) is an autosomal recessive
metabolic disorder caused by a deficiency of the galactose-1-phosphate
uridyltransferase (GALT, EC2.7.7.12) protein due to mutations in the GALT gene.
The aim of this study was to provide a comprehensive and updated mutation
spectrum of GALT in a Korean population. METHODS: Thirteen unrelated patients
screened positive for galactosemia in a newborn screening program were included
in this study. They showed a reduced GALT enzyme activity in red blood cells.
Direct sequencing of the GALT gene and in silico analyses were done to evaluate
the impact of novel variations upon GALT enzyme activity. We also reviewed
previous reports for GALT mutations in Koreans. RESULTS: We identified six novel
likely pathogenic variations including three missense (p.Ala101Asp, p.Tyr165His,
and p.Pro257Thr), one small deletion/insertion [c.826_827delinsAA (p.Ala276Asn)],
one frameshift (p.Asn96Serfs*5), and one splicing (c.378-1G > C) likely
pathogenic variations. The most frequent variation was the Duarte variant (c.940A
> G, 35.3%), followed by c.507G > C (p.Gln169His, 9.6%), among 34 Korean
patients. Other mutations were widely scattered. None of the eight common
mutations used for targeted mutation analysis in Western countries including
p.Gln188Arg, p.Ser135Leu, p.Lys285Asn, p.Leu195Pro, p.Tyr209Cys, p.Phe171Ser,
c.253-2A > G, and a 5 kb deletion, had been found in Koreans until this study.
CONCLUSIONS: Considering the mutation spectrum in Koreans, direct sequence
analysis of entire GALT exons is recommended for accurate diagnosis. The
mutations responsible for GALT deficiency in the Korean population were clearly
different from those of other populations.
PMID- 25124067
TI - Living cardiac tissue slices: an organotypic pseudo two-dimensional model for
cardiac biophysics research.
AB - Living cardiac tissue slices, a pseudo two-dimensional (2D) preparation, have
received less attention than isolated single cells, cell cultures, or Langendorff
perfused hearts in cardiac biophysics research. This is, in part, due to
difficulties associated with sectioning cardiac tissue to obtain live slices.
With moderate complexity, native cell-types, and well-preserved cell-cell
electrical and mechanical interconnections, cardiac tissue slices have several
advantages for studying cardiac electrophysiology. The trans-membrane potential
(Vm) has, thus far, mainly been explored using multi-electrode arrays. Here, we
combine tissue slices with optical mapping to monitor Vm and intracellular Ca(2+)
concentration ([Ca(2+)]i). This combination opens up the possibility of studying
the effects of experimental interventions upon action potential (AP) and calcium
transient (CaT) dynamics in 2D, and with relatively high spatio-temporal
resolution. As an intervention, we conducted proof-of-principle application of
stretch. Mechanical stimulation of cardiac preparations is well-established for
membrane patches, single cells and whole heart preparations. For cardiac tissue
slices, it is possible to apply stretch perpendicular or parallel to the dominant
orientation of cells, while keeping the preparation in a constant focal plane for
fluorescent imaging of in-slice functional dynamics. Slice-to-slice comparison
furthermore allows one to assess transmural differences in ventricular tissue
responses to mechanical challenges. We developed and tested application of axial
stretch to cardiac tissue slices, using a manually-controlled stretching device,
and recorded Vm and [Ca(2+)]i by optical mapping before, during, and after
application of stretch. Living cardiac tissue slices, exposed to axial stretch,
show an initial shortening in both AP and CaT duration upon stretch application,
followed in most cases by a gradual prolongation of AP and CaT duration during
stretch maintained for up to 50 min. After release of sustained stretch, AP
duration (APD) and CaT duration reverted to shorter values. Living cardiac tissue
slices are a promising experimental model for the study of cardiac mechano
electric interactions. The methodology described here can be refined to achieve
more accurate control over stretch amplitude and timing (e.g. using a computer
controlled motorised stage, or by synchronising electrical and mechanical events)
and through monitoring of regional tissue deformation (e.g. by adding motion
tracking).
PMID- 25124068
TI - Mathematical modeling for evolution of heterogeneous modules in the brain.
AB - Modular architecture has been found in most cortical areas of mammalian brains,
but little is known about its evolutionary origin. It has been proposed by
several researchers that maximizing information transmission among subsystems can
be used as a principle for understanding the development of complex brain
networks. In this paper, we study how heterogeneous modules develop in coupled
map networks via a genetic algorithm, where selection is based on maximizing
bidirectional information transmission. Two functionally differentiated modules
evolved from two homogeneous systems with random couplings, which are associated
with symmetry breaking of intrasystem and intersystem couplings. By exploring the
parameter space of the network around the optimal parameter values, it was found
that the optimum network exists near transition points, at which the incoherent
state loses its stability and an extremely slow oscillatory motion emerges.
PMID- 25124069
TI - Memories as bifurcations: realization by collective dynamics of spiking neurons
under stochastic inputs.
AB - How the neural system proceeds from sensory stimuli to generate appropriate
behaviors is a basic question that has not yet been fully answered. In contrast
to the conventional viewpoint, in which the external stimulus dominantly drives
the response behavior, recent studies have revealed that not only external
stimuli, but also intrinsic neural dynamics, contribute to the generation of
response behavior. In particular, spontaneous activity, which is neural activity
without extensive external stimuli, has been found to exhibit similar patterns to
those evoked by external inputs, from time to time. In order to further
understand the role of this spontaneous activity on the response, we propose a
viewpoint, memories-as-bifurcations, that differs from the traditional memories
as-attractors viewpoint. According to this viewpoint, memory is recalled when
spontaneous neural activity is changed to an appropriate output activity upon the
application of an input. After reviewing the previous rate-coding model embodying
this viewpoint, we employ a model of a spiking neuron network that can embed
input/output associations, and study the dynamics of collective neural activity.
The organized neural activity, which matched the target pattern, is shown to be
generated even under application of stochastic input, while the spontaneous
activity, which apparently shows noisy dynamics, is found to exhibit selectively
higher similarity with evoked activities corresponding to embedded target
patterns. These results suggest that such an intrinsic structure in the
spontaneous activity might play a role in generating the higher response. The
relevance of these results to biological neural processing is also discussed.
PMID- 25124070
TI - Bronchoscopic interventions for chronic obstructive pulmonary disease.
AB - Over the past decade, several non-surgical and minimally invasive bronchoscopic
lung volume reduction (BLVR) techniques have been developed to treat patients
with severe chronic obstructive pulmonary disease (COPD). BLVR can be
significantly efficacious, suitable for a broad cohort of patients, and
associated with a solid safety profile at a reasonable expense. The introduction
of BLVR is also expected to accelerate the further development of interventional
pulmonology worldwide. Recently, results from clinical studies on BLVR techniques
have been published, providing valuable information about the procedure's
indications, contraindications, patient-selection criterion and outcomes. BLVR
utilizing one-way endobronchial valves is gaining momentum as an accepted
treatment in regular medical practice because of the identification of best
responders. Patients with a heterogeneous emphysema distribution and without
inter-lobar collateral ventilation show encouraging results. Furthermore, for
patients with collateral ventilation, who are not considered candidates for valve
treatment, and for patients with homogeneous emphysema, the introduction of lung
volume reduction coil treatment is a promising solution. Moreover, with the
development of newer treatment modalities, that is, biochemical sealant and
thermal water vapor, the potential to treat emphysema irrespective of collateral
flow, may be further increased. Nevertheless, patient selection for BLVR
treatment will be crucial for the procedure's success and should be performed
using a multidisciplinary team approach. Consequently, BLVR needs to be
concentrated in high-volume centres that will offer better quality and experience
with treatment challenges and adverse events. This review gives a general
overview of BLVR from an expert and scientific perspective.
PMID- 25124071
TI - Bullet points from SHOT: key messages and recommendations from the Annual SHOT
Report 2013.
PMID- 25124072
TI - Seroepidemiology of human T-cell lymphotropic virus among Iranian adult
thalassemic patients.
AB - BACKGROUND: A large number of transfusion-dependent thalassemic patients is at a
substantial risk for transfusion-transmitted infections. Human T-cell
lymphotropic virus (HTLV) is a blood-borne pathogen and can be transmitted via
cellular products. We aimed to evaluate the seroprevalence of HTLV in transfusion
dependent thalassemic patients referred to Tehran Adult Thalassemia Clinic.
METHODS: From 2008 to 2010, 257 transfusion-dependent thalassemic patients who
referred to Tehran Adult Thalassemia Clinic were enrolled. The seroprevalence of
HTLV, hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV were assessed
using enzyme-linked immunosorbant assay (ELISA). Also, the samples with positive
result for anti-HTLVAb (by ELISA) were reassessed using Western blot for HTLV.
RESULTS: Among the 257 transfusion-dependent thalassemic patients who were tested
for anti-HTLVAb, 29 (11.3%, 95% CI = 7.8-15.6%) were found to be anti-HTLVAb
positive by ELISA and Western blot. No case was detected to be HBsAg positive,
whereas 16% had HBV seroconversion criteria, and more than 95% had anti-HBsAb in
their sera. Also, 103 (40.1%) patients were HCV seropositive, 13 (5.1%) patients
of which were co-infected with HCV/HTLV. Among the HTLV-infected patients, 44.8%
were co-infected with HCV, whereas 39.5% of HTLV-seronegative individuals were
HCV mono-infected (P > 0.05). CONCLUSION: This study showed that transfusion
dependent thalassemic patients were in higher risk for transmission of different
blood-borne pathogens such as HTLV. The screening of HTLV in Iranian blood donors
is recommended.
PMID- 25124073
TI - Pulsed-high-dose dexamethasone as a treatment for pure red cell aplasia following
ABO-incompatible allogeneic stem cell transplantation.
PMID- 25124074
TI - Two cases of platelet transfusion refractoriness and one case of possible FNAIT
caused by antibodies against CD36 in China.
PMID- 25124075
TI - Chaperone network composition in Solanum lycopersicum explored by transcriptome
profiling and microarray meta-analysis.
AB - Heat shock proteins (Hsps) are molecular chaperones primarily involved in
maintenance of protein homeostasis. Their function has been best characterized in
heat stress (HS) response during which Hsps are transcriptionally controlled by
HS transcription factors (Hsfs). The role of Hsfs and Hsps in HS response in
tomato was initially examined by transcriptome analysis using the massive
analysis of cDNA ends (MACE) method. Approximately 9.6% of all genes expressed in
leaves are enhanced in response to HS, including a subset of Hsfs and Hsps. The
underlying Hsp-Hsf networks with potential functions in stress responses or
developmental processes were further explored by meta-analysis of existing
microarray datasets. We identified clusters with differential transcript profiles
with respect to abiotic stresses, plant organs and developmental stages. The
composition of two clusters points towards two major chaperone networks. One
cluster consisted of constitutively expressed plastidial chaperones and other
genes involved in chloroplast protein homeostasis. The second cluster represents
genes strongly induced by heat, drought and salinity stress, including HsfA2 and
many stress-inducible chaperones, but also potential targets of HsfA2 not related
to protein homeostasis. This observation attributes a central regulatory role to
HsfA2 in controlling different aspects of abiotic stress response and tolerance
in tomato.
PMID- 25124076
TI - Vascular endothelial growth factor A polymorphism and risk of Kaposi's sarcoma
herpesvirus viremia in kidney allograft recipients.
AB - BACKGROUND: Kaposi's sarcoma herpesvirus (KSHV) causes Kaposi's sarcoma (KS),
primary effusion lymphoma, and multicentric Castleman's disease in
immunocompromised patients including allograft recipients. Detection of KSHV DNA
in blood, as well as host genetic polymorphisms has been found to be associated
with an increased risk for KS. We investigated an association between single
nucleotide polymorphisms (SNPs) in vascular endothelial growth factor A (VEGFA)
gene region and KSHV viremia in kidney transplant recipients (KTR) in Saudi
Arabia. METHODS: In total, 152 KTR who have survived kidney transplantation for
at least 6 months were included in the study. KSHV viremia was determined by real
time polymerase chain reaction (PCR). Genotyping of SNPs in the VEGFA region was
performed by PCR and direct sequencing, as well as by restriction fragment length
polymorphism. RESULTS: KSHV DNA was detected in 28.9% (n = 44) of the study
population. The A-allele at position C172A VEGFA gene promoter region was found
to be associated with KSHV viremia (odd ratio [OR] = 4.8, P = 0.005). In
addition, the G-allele at position C+405G in the 5'-untranslated region was
associated with KSHV viremia in women, but not in men (OR = 3.98, P = 0.004).
CONCLUSIONS: Our results suggest an association of VEGFA polymorphisms with KSHV
viremia among KTR in this study population. A limitation of our study is that the
results can only be predicated for patients 6 months after kidney transplantation
and should be validated in another cohort with larger sample size.
PMID- 25124077
TI - Study of the usability of spaced retrieval exercise using mobile devices for
Alzheimer's disease rehabilitation.
AB - BACKGROUND: Alzheimer's disease (AD) is an irreversible brain disease that slowly
destroys memory and thinking skills, and eventually the ability to carry out the
simplest daily tasks. Recent studies showed that people with AD might actually
benefit from physical exercises and rehabilitation processes. Studies show that
rehabilitation would also add value in making the day for an individual with AD a
little less foggy, frustrating, isolated, and stressful for as long as possible.
OBJECTIVE: The focus of our work was to explore the use of modern mobile
technology to enable people with AD to improve their abilities to perform
activities of daily living, and hence to promote independence and participation
in social activities. Our work also aimed at reducing the burden on caregivers by
increasing the AD patients' sense of competence and ability to handle behavior
problems. METHODS: We developed ADcope, an integrated app that includes several
modules that targeted individuals with AD, using mobile devices. We have
developed two different user interfaces: text-based and graphic-based. To
evaluate the usability of the app, 10 participants with early stages of AD were
asked to run the two user interfaces of the spaced retrieval memory exercise
using a tablet mobile device. RESULTS: We selected 10 participants with early
stages of AD (average age: 75 years; 6/10, 60% males, 4/10, 40% females). The
average elapsed time per question between the text-based task (14.04 seconds) and
the graphic-based task (12.89 seconds) was significantly different (P=.047).
There was also a significant difference (P<.001) between the average correct
answer score between the text-based task (7.60/10) and the graphic-based task
(8.30/10), and between the text-based task (31.50/100) and the graphic-based task
(27.20/100; P<.001). Correlation analysis for the graphic-based task showed that
the average elapsed time per question and the workload score were negatively
correlated (-.93, and -.79, respectively) to the participants' performance
(P<.001 and P=.006, respectively). CONCLUSIONS: We found that people with early
stages of AD used mobile devices successfully without any prior experience in
using such devices. Participants' measured workload scores were low and posttask
satisfaction in fulfilling the required task was conceivable. Results indicate
better performance, less workload, and better response time for the graphic-based
task compared with the text-based task.
PMID- 25124078
TI - Evaluation of treatment outcomes for patients on first-line regimens in US
President's Emergency Plan for AIDS Relief (PEPFAR) clinics in Uganda: predictors
of virological and immunological response from RV288 analyses.
AB - OBJECTIVES: Viral load (VL) monitoring is recommended, but seldom performed, in
resource-constrained countries. RV288 is a US President's Emergency Plan for AIDS
Relief (PEPFAR) basic programme evaluation to determine the proportion of
patients on treatment who are virologically suppressed and to identify predictors
of virological suppression and recovery of CD4 cell count. Analyses from Uganda
are presented here. METHODS: In this cross-sectional, observational study,
patients on first-line antiretroviral therapy (ART) (efavirenz or
nevirapine+zidovudine/lamivudine) from Kayunga District Hospital and Kagulamira
Health Center were randomly selected for a study visit that included
determination of viral load (HIV-1 RNA), CD4 cell count and clinical chemistry
tests. Subjects were recruited by time on treatment: 6-12, 13-24 or >24 months.
Logistic regression modelling identified predictors of virological suppression.
Linear regression modelling identified predictors of CD4 cell count recovery on
ART. RESULTS: We found that 85.2% of 325 subjects were virologically suppressed
(viral load<47 HIV-1 RNA copies/ml). There was no difference in the proportion of
virologically suppressed subjects by time on treatment, yet CD4 counts were
higher in each successive stratum. Women had higher median CD4 counts than men
overall (406 vs. 294 cells/MUL, respectively; P<0.0001) and in each time-on
treatment stratum. In a multivariate logistic regression model, predictors of
virological suppression included efavirenz use [odds ratio (OR) 0.47; 95%
confidence interval (CI) 0.22-1.02; P=0.057], lower cost of clinic visits (OR
0.815; 95% CI 0.66-1.00; P=0.05), improvement in CD4 percentage (OR 1.06; 95% CI
1.014-1.107; P=0.009), and care at Kayunga vs. Kangulamira (OR 0.47; 95% CI 0.23
0.92; P=0.035). In a multivariate linear regression model of covariates
associated with CD4 count recovery, time on highly active antiretroviral therapy
(ART) (P<0.0001), patient satisfaction with care (P=0.038), improvements in total
lymphocyte count (P<0.0001) and haemoglobin concentration (P=0.05) were
positively associated, whereas age at start of ART (P=0.0045) was negatively
associated with this outcome. CONCLUSIONS: High virological suppression rates are
achievable on first-line ART in Uganda. The odds of virological suppression were
positively associated with efavirenz use and improvements in CD4 cell percentage
and total lymphocyte count and negatively associated with the cost of travel to
the clinic. CD4 cell reconstitution was positively associated with CD4 count at
study visit, time on ART, satisfaction with care at clinic, haemoglobin
concentration and total lymphocyte count and negatively associated with age.
PMID- 25124079
TI - Stigma and the perpetuation of obesity.
AB - Even as obesity rates reach new highs, the social stigmatization of obesity seems
to be strengthening and globalizing. This review identifies at least four
mechanisms by which a pervasive environment of fat stigma could reinforce high
body weights or promote weight gain, ultimately driving population-level obesity.
These are direct effects through behavior change because of feeling judged, and
indirect effects of social network changes based on stigmatizing actions and
decisions by others, psychosocial stress from feeling stigmatized, and the
structural effects of discrimination. Importantly, women and children appear
especially vulnerable to these mechanisms. The broader model provides an improved
basis to investigate the role of stigma in driving the etiology of obesity, and
explicates how individual, interpersonal, and structural dimensions of stigma are
connected to variation in health outcomes, including across generations.
PMID- 25124080
TI - Effects of the exercise-inducible myokine irisin on malignant and non-malignant
breast epithelial cell behavior in vitro.
AB - Exercise has been shown to reduce risk and improve prognosis of several types of
cancers. Irisin is a myokine linked to exercise and lean body mass, which is
thought to favorably alter metabolism systemically, potentially providing benefit
for metabolic disease (including cancer). We evaluated the effects of various
concentrations of irisin (with and without post-translational modifications) on
malignant and non-malignant breast epithelial cell number, migration and
viability. Irisin significantly decreased cell number, migration and viability in
malignant MDA-MB-231 cells, without affecting non-malignant MCF-10a cells.
Moreover, irisin enhanced the cytotoxic effect of doxorubicin (Dox) when added to
a wide spectrum of irisin concentrations in the malignant cell type (with
simultaneous reduction in Dox uptake), which was not observed in non-malignant
MCF-10a cells. Additionally, we found that irisin decreases malignant cell
viability in part through stimulation of caspase activity leading to apoptotic
death. Interestingly, we found that irisin suppresses NFkappaB activation, an
opposite effect of other myokines such as tumor necrosis factor alpha (TNF
alpha). Our observations suggest that irisin may offer therapeutic benefits for
breast cancer prevention and treatment possibly through an anti-inflammatory
response, induction of apoptotic cell death, or through enhanced tumor
sensitivity to common antineoplastic agents such as Dox.
PMID- 25124081
TI - Resmethrin, the first modern pyrethroid insecticide.
AB - The discovery of resmethrin almost five decades ago was the seminal event in the
development of pyrethroid insecticides as important pest management tools, the
value of which endures to this day. This brief review considers the development
of pyrethroids from the perspective of the discovery of resmethrin. I describe
the pathway to the discovery of resmethrin and the unique properties that
differentiated it from the pyrethrins and earlier synthetic pyrethroids is
described. I also summarize information on metabolic fate and mechanisms of
selective toxicity, first elucidated with resmethrin, that have shaped our
understanding of pyrethroid toxicology since that time. Finally, I review the
discovery pathway that led from resmethrin to the development of the first
photostable, agriculturally useful pyrethroids that established the importance of
this insecticide class.
PMID- 25124082
TI - In vivo magnetic resonance imaging of tumor protease activity.
AB - Increased expression of cathepsins has diagnostic as well as prognostic value in
several types of cancer. Here, we demonstrate a novel magnetic resonance imaging
(MRI) method, which uses poly-L-glutamate (PLG) as an MRI probe to map cathepsin
expression in vivo, in a rat brain tumor model. This noninvasive, high-resolution
and non-radioactive method exploits the differences in the CEST signals of PLG in
the native form and cathepsin mediated cleaved form. The method was validated in
phantoms with known physiological concentrations, in tumor cells and in an animal
model of brain tumor along with immunohistochemical analysis. Potential
applications in tumor diagnosis and evaluation of therapeutic response are
outlined.
PMID- 25124083
TI - Community-based family-style group homes for children orphaned by AIDS in rural
China: an ethnographic investigation.
AB - As the number of children orphaned by AIDS (Acquired Immunodeficiency Syndrome)
has reached 17.3 million, most living in resource-poor settings, interest has
grown in identifying and evaluating appropriate care arrangements for them. In
this study, we describe the community-based family-style group homes ('group
homes') in rural China. Guided by an ecological framework of children's
wellbeing, we conducted a series of ethnographic observations, in-depth
interviews and group discussions in the rural areas of Henan Province, which has
been severely impacted by the AIDS endemic through commercial blood collection.
Based on our observations and discussions, group homes appear to provide stable
and safe living environments for children orphaned by AIDS. Adequate financial
support from non-government organizations (NGOs) as well as the central and
provincial governments has ensured a low child-caregiver ratio and attention to
the basic needs of the children at group homes. The foster parents were selected
from the local community and appear to have adequate qualifications and
dedication. They receive a monthly stipend, periodical evaluation and parenting
consultation from supporting NGOs. The foster parents and children in the group
homes have formed strong bonds. Both children and foster parents reported
positively on health and education. Characteristics of community-based group
homes can be replicated in other care arrangements for AIDS orphans in resource
poor settings for the optimal health outcomes of those vulnerable children. We
also call for capacity building for caregivers and communities to provide
sustainable and supportive living environment for these children.
PMID- 25124084
TI - African stakeholders' views of research options to improve nutritional status in
sub-Saharan Africa.
AB - BACKGROUND: Setting research priorities for improving nutrition in Africa is
currently ad hoc and there is a need to shift the status quo in the light of slow
progress in reducing malnutrition. This study explored African stakeholders'
views on research priorities in the context of environmental and socio
demographic changes that will impact on nutritional status in Africa in the
coming years. METHODS: Using Multi-Criteria Mapping, quantitative and qualitative
data were gathered from 91 stakeholders representing 6 stakeholder groups (health
professionals, food Industry, government, civil society, academics and research
funders) in Benin, Mozambique, South Africa, Tanzania, Togo and Uganda.
Stakeholders appraised six research options (ecological nutrition, nutritional
epidemiology, community nutrition interventions, behavioural nutrition, clinical
nutrition and molecular nutrition) for how well they could address malnutrition
in Africa. RESULTS: Impact (28.3%), research efficacy (23.6%) and social
acceptability (22.4%) were the criteria chosen the most to evaluate the
performance of research options. Research on the effectiveness of community
interventions was seen as a priority by stakeholders because they were perceived
as likely to have an impact relatively quickly, were inexpensive and cost
effective, involved communities and provided direct evidence of what works.
Behavioural nutrition research was also highly appraised. Many stakeholders,
particularly academics and government were optimistic about the value of
ecological nutrition research (the impact of environmental change on nutritional
status). Research funders did not share this enthusiasm. Molecular nutrition was
least preferred, considered expensive, slow to have an impact and requiring
infrastructure. South Africa ranked clinical and molecular nutrition the highest
of all countries. CONCLUSION: Research funders should redirect research funds in
Africa towards the priorities identified by giving precedence to develop the
evidence for effective community nutrition interventions. Expanding research
funding in behavioural and ecological nutrition was also valued and require multi
disciplinary collaborations between nutritionists, social scientists,
agricultural and climate change scientists.
PMID- 25124086
TI - The role of environmental context, faith, and patient satisfaction in HIV
prevention among African American women.
PMID- 25124085
TI - Asymmetric gold-catalyzed lactonizations in water at room temperature.
AB - Asymmetric gold-catalyzed hydrocarboxylations are reported that show broad
substrate scope. The hydrophobic effect associated with in situ-formed aqueous
nanomicelles gives good to excellent ee's of product lactones. In-flask product
isolation, along with the recycling of the catalyst and the reaction medium, are
combined to arrive at an especially environmentally friendly process.
PMID- 25124087
TI - Posttraumatic disease of the palmar fascia.
PMID- 25124088
TI - Peripheral nerve injuries: advancing the field through research, collaboration,
and education.
AB - The Andrew J. Weiland Medal is presented each year by the American Society for
Surgery of the Hand and the American Foundation for Surgery of the Hand for a
body of work related to hand surgery research. This essay, awarded the Weiland
Medal in 2013, focuses on advancing the field of peripheral nerve injuries
through research, collaboration, and education.
PMID- 25124089
TI - Identifying optimal biomarker combinations for treatment selection via a robust
kernel method.
AB - Treatment-selection markers predict an individual's response to different
therapies, thus allowing for the selection of a therapy with the best predicted
outcome. A good marker-based treatment-selection rule can significantly impact
public health through the reduction of the disease burden in a cost-effective
manner. Our goal in this article is to use data from randomized trials to
identify optimal linear and nonlinear biomarker combinations for treatment
selection that minimize the total burden to the population caused by either the
targeted disease or its treatment. We frame this objective into a general problem
of minimizing a weighted sum of 0-1 loss and propose a novel penalized
minimization method that is based on the difference of convex functions algorithm
(DCA). The corresponding estimator of marker combinations has a kernel property
that allows flexible modeling of linear and nonlinear marker combinations. We
compare the proposed methods with existing methods for optimizing treatment
regimens such as the logistic regression model and the weighted support vector
machine. Performances of different weight functions are also investigated. The
application of the proposed method is illustrated using a real example from an
HIV vaccine trial: we search for a combination of Fc receptor genes for
recommending vaccination in preventing HIV infection.
PMID- 25124090
TI - Norwegian nursing and medical students' perception of interprofessional teamwork:
a qualitative study.
AB - BACKGROUND: Little is known about the ways in which nursing and medical students
perceive and understand their roles in interprofessional teamwork. A 2010 report
by the World Health Organization highlights the importance of students'
understanding of teamwork in healthcare, and their ability to be effective team
players. This study aims at describing nursing and medical students' perceptions
of interprofessional teamwork, focusing on experiences and recommendations that
can be used to guide future educational efforts. METHODS: The study uses a
qualitative research design. Data were collected from four focus group
interviews: two homogenous groups (one with medical students, one with nursing
students) and two mixed groups (medical and nursing students). RESULTS: The
results show that traditional patterns of professional role perception still
prevail and strongly influence students' professional attitudes about taking
responsibility and sharing responsibility across disciplinary and professional
boundaries. It was found that many students had experienced group cultures
detrimental to team work. Focusing on clinical training, the study found a
substantial variation in perception with regard to the different arenas for
interprofessional teamwork, ranging from arenas with collaborative learning to
arenas characterized by distrust, confrontation, disrespect and hierarchical
structure. CONCLUSIONS: This study underlines the importance of a stronger focus
on interprofessional teamwork in health care education, particularly in clinical
training. The study results suggest that the daily rounds and pre-visit
"huddles," or alternatively psychiatric wards, offer arenas suitable for
interprofessional training, in keeping with the students' assessments and
criteria proposed in previous studies.
PMID- 25124091
TI - Voiding diaries: adherence in the clinical setting.
AB - INTRODUCTION AND HYPOTHESIS: The objective was to document adherence with 24-h
voiding diaries in the evaluation of routine urogynecology patients. METHODS:
This was a cross-sectional study of 200 patients presenting for initial
urogynecological consultation. All were mailed a standardized packet prior to
their visit, including a 24-h voiding diary. Upon arrival, subjects were asked to
complete a brief survey. Eight questions targeted those that completed the diary
("completers"); 3 targeted those that did not ("noncompleters"). "Completers"
were further sub-classified based on survey responses. Those recording each void
immediately were termed "appropriate completers." Others were considered
"inappropriate completers." Demographics and other data were obtained from the
medical records. RESULTS: Eleven women were excluded for recording more than 24 h
of data. Of the 189 remaining subjects, 157 (83 %) completed the diary. Many
"noncompleters" were unaware of the diary (54 %). Others chose not to complete
it, most commonly citing "don't think it applies" (25 %). On univariate analysis
"completers" were older (p = 0.049), with more complaints of mixed incontinence
(p = 0.001). Fifty-four percent of "completers" were deemed "appropriate."
"Appropriate completers" voided more frequently (p = 0.024) than "inappropriate
completers." After multivariate analyses, however, only lower parity and
unemployed status were associated with appropriate diary completion.
Reassuringly, the majority, 77 %, believed that the diary responses were
reflective of their typical behavior, and voiding frequency on the diary
correlated with self-report during their medical history (rs = 0.483, p < 0.001).
CONCLUSIONS: Although compliance with voiding diaries is reasonably high in the
office setting, adherence to instructions is less optimal. Strategies to improve
ease of use could benefit future patient care.
PMID- 25124092
TI - Pelvic organ prolapse surgical management in Portugal and FDA safety
communication have an impact on vaginal mesh.
AB - INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) surgery has lately
gained importance in gynecological practice. This study aims to characterize the
evolution of POP surgical procedures conducted in Portugal in the last decade and
the impact of an FDA 2011 safety communication on mesh POP surgeries. METHODS:
Trends in the surgical management of POP were assessed using the Portuguese
National Medical Registry. We considered all records of women with diagnosis of
genital prolapse from 1 January 2000 to 31 December 2012. Additionally, we also
conducted a survey among members of the Portuguese Society of Urogynecology to
evaluate current practices in the surgical management of POP. RESULTS: From 2000
to 2012, 46,819 diagnoses of genital prolapse were registered, with a 105 %
increase during the study period (2,368 in 2000 to 4,941 in 2012). POP mesh
surgery represented only 6 % of total prolapse diagnoses, but mesh use greatly
increased up to 2011, when only a slight increase was registered. Among
gynecologists who responded to the questionnaire, there was considerable
variability on the procedures of choice to treat POP. Fifty-seven per cent of
respondents performed vaginal mesh POP surgery, but only 27 % of those actually
reported having changed their practice after the FDA 2011 safety communication.
CONCLUSIONS: Surgical procedures for POP conducted in Portugal greatly increased
over the last decade. The use of surgical meshes is still limited, but despite
FDA safety communication it has increased over the years, with a slight increase
in 2012, which illustrates the need for further analyses in the coming years.
PMID- 25124093
TI - The genetic control of aposematic black pigmentation in hemimetabolous insects:
insights from Oncopeltus fasciatus.
AB - Variations in body pigmentation, encompassing both the range of specific colors
as well as the spatial arrangement of those colors, are among the most noticeable
and lineage-specific insect features. However, the genetic mechanisms responsible
for generating this diversity are still limited to several model species that are
primarily holometabolous insects. To address this lack of knowledge, we utilize
Oncopeltus fasciatus, an aposematic hemimetabolous insect, as a new model to
study insect pigmentation. First, to determine the genetic regulation of black
pigment production in Oncopeltus, we perform an RNAi analysis on three core genes
involved in the melanin pathway, tyrosine hydroxylase (TH), dopa decarboxylase
(DDC), and laccase 2 (lac2). The black pigmentation is affected in all instances,
showing that the black pigments in this species are derived from the melanin
pathway. The results of the DDC RNAi are particularly informative because they
reveal that it is Dopamine melanin, not DOPA melanin, which is the predominant
component of black pigments in Oncopeltus. Second, we test whether pigmentation
follows a two-step model where the spatial pre-mapping of enzymatic activity is
followed by vein-dependent transportation of melanin substances. We confirm the
existence of the first step by observing that premature wings develop black
pigmentation when exposed to melanin precursors. In addition, we provide evidence
for the second step by showing that wing melanin patterning is disrupted when
vein transportation is halted. These findings bring novel insights from a
hemimetabolous species and establish a framework for subsequent studies on the
mechanisms of pigment production and patterning responsible for variations in
insect coloration.
PMID- 25124094
TI - Regulatory volume increase in astrocytes exposed to hypertonic medium requires
beta1 -adrenergic Na(+) /K(+) -ATPase stimulation and glycogenolysis.
AB - The cotransporter of Na(+) , K(+) , 2Cl(-) , and water, NKKC1, is activated under
two conditions in the brain, exposure to highly elevated extracellular K(+)
concentrations, causing astrocytic swelling, and regulatory volume increase in
cells shrunk in response to exposure to hypertonic medium. NKCC1-mediated
transport occurs as secondary active transport driven by Na(+) /K(+) -ATPase
activity, which establishes a favorable ratio for NKCC1 operation between
extracellular and intracellular products of the concentrations of Na(+) , K(+) ,
and Cl(-) * Cl(-) . In the adult brain, astrocytes are the main target for NKCC1
stimulation, and their Na(+) /K(+) -ATPase activity is stimulated by elevated
K(+) or the beta-adrenergic agonist isoproterenol. Extracellular K(+)
concentration is normal during regulatory volume increase, so this study
investigated whether the volume increase occurred faster in the presence of
isoproterenol. Measurement of cell volume via live cell microscopic imaging
fluorescence to record fluorescence intensity of calcein showed that this was the
case at isoproterenol concentrations of >=1 uM in well-differentiated mouse
astrocyte cultures incubated in isotonic medium with 100 mM sucrose added. This
stimulation was abolished by the beta1 -adrenergic antagonist betaxolol, but not
by ICI118551, a beta2 -adrenergic antagonist. A large part of the beta1
adrenergic signaling pathway in astrocytes is known. Inhibitors of this pathway
as well as the glycogenolysis inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol
hydrochloride and the NKCC1 inhibitors bumetanide and furosemide abolished
stimulation by isoproterenol, and it was weakened by the Na(+) /K(+) -ATPase
inhibitor ouabain. These observations are of physiological relevance because
extracellular hypertonicity occurs during intense neuronal activity. This might
trigger a regulatory volume increase, associated with the post-excitatory
undershoot.
PMID- 25124095
TI - Relationship between mid-trimester ultrasound fetal liver length measurements and
gestational diabetes mellitus.
AB - BACKGROUND: The aim of the present study was to investigate the relationship
between mid-trimester ultrasound fetal liver length (FLL) and gestational
diabetes mellitus (GDM) in a high-risk population. METHODS: A prospective study
was performed in 331 women with singleton pregnancies who were at high risk of
GDM and were undergoing a mid-trimester ultrasound examination. The ultrasound
scan at 23 weeks gestation was followed by a 100-g oral glucose tolerance test
(OGTT) at 24 weeks gestation. Correlations between FLL and OGTT results at
different time points were tested. Receiver operating characteristic (ROC)
analysis of FLL as a potential prognostic factor for GDM was also performed.
RESULTS: In GDM patients, there was a significant positive correlation (P < 0.01)
between FLL and OGTT glycemia immediately before and 60, 120, and 180 min after
glucose intake. Mean FLL in GDM was significantly higher than in healthy subjects
(41.04 vs 31.09 mm, respectively; P < 0.001). When tested as a potential
prognostic factor for GDM, fetal liver measurements showed excellent diagnostic
performance. The ROC analysis established a cut-off value of FLL of 39 mm for the
prediction GDM, with sensitivity of 71.76%, specificity 97.56%, positive
predictive value 91.0%, and negative predictive value 90.9%. The usefulness of
FLL measurements was supported by a high area under the ROC curve (90.5%).
CONCLUSION: In conclusion, there is a strong correlation between FLL and OGTT
results, with FLL possibly serving as a valid marker for the prediction of GDM in
high-risk populations.
PMID- 25124096
TI - A transcriptome approach to ecdysozoan phylogeny.
AB - The monophyly of Ecdysozoa, which comprise molting phyla, has received strong
support from several lines of evidence. However, the internal relationships of
Ecdysozoa are still contended. We generated expressed sequence tags from a
priapulid (penis worm), a kinorhynch (mud dragon), a tardigrade (water bear) and
five chelicerate taxa by 454 transcriptome sequencing. A multigene alignment was
assembled from 63 taxa, which comprised after matrix optimization 24,249 amino
acid positions with high data density (2.6% gaps, 19.1% missing data).
Phylogenetic analyses employing various models support the monophyly of
Ecdysozoa. A clade combining Priapulida and Kinorhyncha (i.e. Scalidophora) was
recovered as the earliest branch among Ecdysozoa. We conclude that Cycloneuralia,
a taxon erected to combine Priapulida, Kinorhyncha and Nematoda (and others), are
paraphyletic. Rather Arthropoda (including Onychophora) are allied with Nematoda
and Tardigrada. Within Arthropoda, we found strong support for most clades,
including monophyletic Mandibulata and Pancrustacea. The phylogeny within the
Euchelicerata remained largely unresolved. There is conflicting evidence on the
position of tardigrades: While Bayesian and maximum likelihood analyses of only
slowly evolving genes recovered Tardigrada as a sister group to Arthropoda,
analyses of the full data set, and of subsets containing genes evolving at fast
and intermediate rates identified a clade of Tardigrada and Nematoda. Notably,
the latter topology is also supported by the analyses of indel patterns.
PMID- 25124097
TI - Evolutionary relationships in the medicinally important genus Fritillaria L.
(Liliaceae).
AB - Fritillaria (Liliaceae) is a genus of approximately 140 species of bulbous
perennial plants that includes taxa of both horticultural and medicinal
importance. As well as being commercially valuable, Fritillaria species have
attracted attention because of their exceptionally large genome sizes, with all
values recorded to date in excess of 30Gb. Despite such interest in the genus,
phylogenetic relationships between the majority of species have remained
untested. Here we present the first phylogenetic reconstruction of relationships
to encompass most of the currently recognised species diversity in the genus.
Three regions of the plastid genome were sequenced in 117 individuals of
Fritillaria, representing 92 species (c. 66% of the genus) and in representatives
of nine other genera of Liliaceae. Eleven low-copy nuclear gene regions were also
screened in selected species for their potential utility. Phylogenetic analysis
of a combined plastid dataset using maximum parsimony and Bayesian inference
provided support for the monophyly of the majority of currently recognised
subgenera. However, subgenus Fritillaria, which is by far the largest of the
subgenera and includes the most important species used in traditional Chinese
medicine, is found to be polyphyletic. Moreover, several taxa that were
represented by multiple individuals show evidence of species non-monophyly. The
Japanese endemic subgenus Japonica, which contains the species with the largest
recorded genome size for any diploid plant, is resolved as sister to the
predominantly Middle Eastern and Central Asian subgenus Rhinopetalum. Whilst
relationships between most of the major Fritillaria lineages can now be resolved,
our results also highlight the need for data from additional independently
evolving loci; an endeavour that may be particularly challenging in light of the
huge nuclear genomes found in these plants.
PMID- 25124098
TI - Should genes with missing data be excluded from phylogenetic analyses?
AB - Phylogeneticists often design their studies to maximize the number of genes
included but minimize the overall amount of missing data. However, few studies
have addressed the costs and benefits of adding characters with missing data,
especially for likelihood analyses of multiple loci. In this paper, we address
this topic using two empirical data sets (in yeast and plants) with well-resolved
phylogenies. We introduce varying amounts of missing data into varying numbers of
genes and test whether the benefits of excluding genes with missing data outweigh
the costs of excluding the non-missing data that are associated with them. We
also test if there is a proportion of missing data in the incomplete genes at
which they cease to be beneficial or harmful, and whether missing data
consistently bias branch length estimates. Our results indicate that adding
incomplete genes generally increases the accuracy of phylogenetic analyses
relative to excluding them, especially when there is a high proportion of
incomplete genes in the overall dataset (and thus few complete genes). Detailed
analyses suggest that adding incomplete genes is especially helpful for resolving
poorly supported nodes. Given that we find that excluding genes with missing data
often decreases accuracy relative to including these genes (and that decreases
are generally of greater magnitude than increases), there is little basis for
assuming that excluding these genes is necessarily the safer or more conservative
approach. We also find no evidence that missing data consistently bias branch
length estimates.
PMID- 25124099
TI - Selective adsorption of metoprolol enantiomers using 2-hydroxypropyl-beta
cyclodextrin cross-linked multiwalled carbon nanotube.
AB - This study investigates the ability of functionalized multiwalled carbon
nanotubes (MWCNTs) for enantio-separation of metoprolol chiral forms.
2Hydroxypropyl-beta-cyclodextrin (2HP-beta-CD) was applied as a chiral selector
to functionalize carbon nanotubes (CNTs). The modified multiwalled CNT samples
were characterized using scanning electron microscopy and Fourier transform
infrared spectroscopy. The results of analyses showed that CNTs were successfully
cross-linked with 2HP-beta-CD. To evaluate the enantio-separation property of the
products, the separation of metoprolol chiral forms on the initial and final
products was examined. Further, UV-visible spectroscopy and polarimeter analyses
were used for characterization. The results indicate that MWCNT does not have any
intrinsic enantio-separation ability, although its selectivity for enantio
separation can be enhanced by cross-linking it to 2HP-beta-CD. Moreover, the
optimal mass of adsorbent as well as optimal mass of functional groups is
estimated to achieve maximum enantio-separation efficiency. The results indicate
that applying large amounts of 2HP-beta-CD to CNTs functionalization decreases
the cross-linking efficiency, which consequently reduces enantio-separation
efficiency.
PMID- 25124100
TI - The advantage of professional organizations as advocates for improved funding of
maternal and child health services in Uganda.
AB - The attainment of United Nations Millennium Development Goal 5 has proven elusive
for many countries. Efforts to reduce maternal mortality require concerted
evidence-based efforts from all key players, including professional
organizations. The Association of Obstetricians and Gynaecologists of Uganda used
the results of maternal and perinatal death review to develop and pilot advocacy
programs with parliamentarians, media, and government that aimed to improve
maternal and newborn health in Uganda. This work translated to further
parliamentary debate on the topic, increased resource allocation by government,
and improved media-related public education.
PMID- 25124101
TI - One-year evaluation of the impact of an emergency obstetric and neonatal care
training program in Western Kenya.
AB - OBJECTIVE: To determine the impact of introducing an emergency obstetric and
neonatal care training program on maternal and perinatal morbidity and mortality
at Moi Teaching and Referral Hospital, Eldoret, Kenya. METHODS: A prospective
chart review was conducted of all deliveries during the 3-month period (November
2009 to January 2010) before the introduction of the Advances in Labor and Risk
Management International Program (AIP), and in the 3-month period (August
November 2011) 1 year after the introduction of the AIP. All women who were
admitted and delivered after 28 weeks of pregnancy were included. The primary
outcome was the direct obstetric case fatality rate. RESULTS: A total of 1741
deliveries occurred during the baseline period and 1812 in the postintervention
period. Only one mother died in each period. However, postpartum hemorrhage rates
decreased, affecting 59 (3.5%) of 1669 patients before implementation and 40
(2.3%) of 1751 afterwards (P=0.029). The number of patients who received oxytocin
increased from 829 (47.6%) to 1669 (92.1%; P<0.001). Additionally, the number of
neonates with 5-minute Apgar scores of less than 5 reduced from 133 (7.7%) of
1717 to 95 (5.4%) of 1745 (P=0.006). CONCLUSION: The introduction of the AIP
improved maternal outcomes. There were significant differences related to use of
oxytocin and postpartum hemorrhage.
PMID- 25124102
TI - A chromosomal 5q31.1 gain involving PITX1 causes Liebenberg syndrome.
PMID- 25124103
TI - Increased blood glucose is related to disturbed cerebrovascular pressure
reactivity after traumatic brain injury.
AB - BACKGROUND: Increased blood glucose and impaired pressure reactivity (PRx) after
traumatic brain injury (TBI) are both known to correlate with unfavorable patient
outcome. However, the relationship between these two variables is unknown.
METHODS: To test the hypothesis that increased blood glucose leads to increased
PRx, we retrospectively analyzed data from 86 traumatic brain injured patients
admitted to the Neurocritical Care Unit. Data analyzed included arterial glucose
concentration, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and
end-tidal CO2. PRx was calculated as the moving correlation coefficient between
averaged (10 seconds) arterial blood pressure and ICP. One arterial glucose
concentration and one time-aligned PRx value were obtained for each patient,
during each day until the fifth day after ictus. RESULTS: Mean arterial glucose
concentrations during the first 5 days since ictus were positively correlated
with mean PRx (Pearson correlation coefficient = 0.25, p = 0.02). The correlation
was strongest on the first day after injury (Pearson correlation coefficient =
0.47, p = 0.008). CONCLUSION: Our preliminary findings indicate that increased
blood glucose may impair cerebrovascular reactivity, potentially contributing to
a mechanistic link between increased blood glucose and poorer outcome after TBI.
PMID- 25124104
TI - Plasmapheresis may be an option in urgent management of heparin-induced
thrombocytopenia in the setting of acute intracerebral hemorrhage.
AB - BACKGROUND: We report a case of heparin-induced thrombocytopenia (HIT) that was
complicated by acute intracerebral hemorrhage (ICH) and bilateral adrenal
hemorrhage. In the setting of worsening thrombocytopenia, the risk of expansion
of ICH and additional thrombotic events is concerning; hence, we employed
plasmapheresis to reduce thrombotic risk. METHODS: We followed serial daily
heparin antibody enzyme-linked immunosorbent assay (ELISA) optical density
measurements as well as heparin-induced platelet aggregation (HIPA) assays on
both pre- and post-pheresis samples in order to objectively determine when
thrombotic risk was sufficiently decreased. RESULTS: After four cycles of
plasmapheresis, both heparin antibody ELISA and HIPA assays became negative.
CONCLUSION: This case helps illustrate the utility of plasmapheresis in
management of HIT when anticoagulation is contraindicated.
PMID- 25124106
TI - Ventriculostomy-Associated Infection (VAI): In Search of a Definition.
PMID- 25124105
TI - Accuracy of nimodipine gel extraction.
AB - INTRODUCTION: Until recently, use of nimodipine in aneurysmal subarachnoid
hemorrhage patients unable to swallow required extraction of gel from inside the
commercially available capsule. Despite the Black-Box warning against inadvertent
intravenous administration, bedside extraction of the gel from the capsule
continues to be a common practice in some institutions. The accuracy of bedside
extraction has not been formally evaluated. METHODS: Twenty-eight nurses from the
neurology and neurosurgical ICUs at a single center attempted to extract
nimodipine gel from 2 capsules, each using the method currently approved by the
US FDA. The primary outcome was mean weight of extracted gel per capsule, which
was compared to both gel weight from batch compounded pharmacy syringes and a pre
calculated appropriate weight for 30 mg nimodipine gel. RESULTS: Simulated
bedside extraction provided lower yield than pharmacy-compounded syringes (22.6
+/- 4.6 mg vs 30.4 +/- 0.59 mg, p = 0.001). Bedside extraction provided
inconsistent and low yield (75.4 +/- 15.32 % of possible dose extracted, p =
0.0001 for comparison of means between bedside extraction syringes and predicted
gel weight). Pharmacy-compounded syringes provided consistent high yield (101.3
+/- 2.0 % of possible dose extracted, p = 0.14 for comparison of means between
pharmacy syringes and predicted gel weight). CONCLUSION: Combined with reports of
significant patient harm and death with inadvertent intravenous administration,
this study suggests that there is no role for bedside extraction of nimodipine in
clinical practice.
PMID- 25124107
TI - Prostate cancer mortality outcomes and patterns of primary treatment for
Aboriginal men in New South Wales, Australia.
AB - OBJECTIVE: To compare prostate cancer mortality for Aboriginal and non-Aboriginal
men and to describe prostate cancer treatments received by Aboriginal men.
PATIENTS AND METHODS: We analysed cancer registry records for all men diagnosed
with prostate cancer in New South Wales (NSW) in 2001-2007 linked to hospital
inpatient episodes and deaths. More detailed information on androgen-deprivation
therapy and radiotherapy was obtained from medical records for 87 NSW Aboriginal
men diagnosed in 2000-2011. The main outcomes were primary treatment for, and
death from, prostate cancer. Analysis included Cox proportional hazards
regression and logistic regression. RESULTS: There were 259 Aboriginal men among
35,214 prostate cancer cases diagnosed in 2001-2007. Age and spread of disease at
diagnosis were similar for Aboriginal and non-Aboriginal men. Prostate cancer
mortality 5 years after diagnosis was higher for Aboriginal men (17.5%, 95%
confidence interval (CI) 12.4-23.3) than non-Aboriginal men (11.4%, 95% CI 11.0
11.8). Aboriginal men were 49% more likely to die from prostate cancer (hazard
ratio 1.49, 95% CI 1.07-1.99) after adjusting for differences in demographic
factors, stage at diagnosis, health access and comorbidities. Aboriginal men were
less likely to have a prostatectomy for localised or regional cancer than non
Aboriginal men (adjusted odds ratio 0.60, 95% CI 0.40-0.91). Of 87 Aboriginal men
with full staging and treatment information, 60% were diagnosed with localised
disease. Of these, 38% had a prostatectomy (+/- radiotherapy), 29% had
radiotherapy only and 33% had neither. CONCLUSION: More research is required to
explain differences in treatment and mortality for Aboriginal men with prostate
cancer compared with non-Aboriginal men. In the meantime, ongoing monitoring and
efforts are needed to ensure Aboriginal men have equitable access to best care.
PMID- 25124109
TI - Strong anisotropic dynamics of ultra-confined water.
AB - Dynamics of water confined in ~5 A diameter channels of beryl and cordierite
single crystals were studied by using inelastic (INS) and quasielastic (QENS)
neutron scattering. The INS spectra for both samples were similar and showed that
there are no hydrogen bonds acting on water molecule, which experiences strong
anisotropic potential, steep along the channels and very soft perpendicular to
it. The high-resolution (3.4 MUeV) QENS data revealed gradual freezing out of the
water molecule dynamics for both minerals at temperatures below about 80 K when
the scattering momentum transfer was parallel to the channels, but not when it
was perpendicular to the channels. The QENS study with medium energy resolution
(0.25 meV) of the beryl with the scattering momentum transfer along the channels
showed gradual freezing out of water molecule dynamics at temperatures below
about 200 K, whereas at higher temperatures the data could be described as 2-fold
rotational jumps about the axis coinciding with the direction of the dipole
moment (that is, perpendicular to the channels), with a residence time of 5.5 ps
at 225 K. The energy resolution dependence of the apparent dynamics freezing
temperature suggests gradual slowing down of the rotational jumps as the
temperature is decreased, until the associated QENS broadening can no longer be
detected, rather than actual freezing.
PMID- 25124108
TI - CRF-based models of protein surfaces improve protein-protein interaction site
predictions.
AB - BACKGROUND: The identification of protein-protein interaction sites is a
computationally challenging task and important for understanding the biology of
protein complexes. There is a rich literature in this field. A broad class of
approaches assign to each candidate residue a real-valued score that measures how
likely it is that the residue belongs to the interface. The prediction is
obtained by thresholding this score.Some probabilistic models classify the
residues on the basis of the posterior probabilities. In this paper, we introduce
pairwise conditional random fields (pCRFs) in which edges are not restricted to
the backbone as in the case of linear-chain CRFs utilized by Li et al. (2007). In
fact, any 3D-neighborhood relation can be modeled. On grounds of a generalized
Viterbi inference algorithm and a piecewise training process for pCRFs, we
demonstrate how to utilize pCRFs to enhance a given residue-wise score-based
protein-protein interface predictor on the surface of the protein under study.
The features of the pCRF are solely based on the interface predictions scores of
the predictor the performance of which shall be improved. RESULTS: We performed
three sets of experiments with synthetic scores assigned to the surface residues
of proteins taken from the data set PlaneDimers compiled by Zellner et al.
(2011), from the list published by Keskin et al. (2004) and from the very recent
data set due to Cukuroglu et al. (2014). That way we demonstrated that our pCRF
based enhancer is effective given the interface residue score distribution and
the non-interface residue score are unimodal.Moreover, the pCRF-based enhancer is
also successfully applicable, if the distributions are only unimodal over a
certain sub-domain. The improvement is then restricted to that domain. Thus we
were able to improve the prediction of the PresCont server devised by Zellner et
al. (2011) on PlaneDimers. CONCLUSIONS: Our results strongly suggest that pCRFs
form a methodological framework to improve residue-wise score-based protein
protein interface predictors given the scores are appropriately distributed. A
prototypical implementation of our method is accessible at
http://ppicrf.informatik.uni-goettingen.de/index.html.
PMID- 25124110
TI - Development of the Japanese version of the Minneapolis-Manchester Quality of Life
Survey of Health - Adolescent Form (MMQL-AF) and investigation of its reliability
and validity.
AB - BACKGROUND: There are very few reliable and valid measures in Japan assessing
health-related quality of life (HRQOL) in children with cancer. The present study
aimed to develop a Japanese version of the Minneapolis-Manchester Quality of Life
Survey of Health Adolescent Form (MMQL-AF), which is a measure for assessing the
HRQOL of childhood cancer survivors, and investigate its reliability and
validity. METHODS: Participants were 141 children with cancer who had been off
therapy for more than one year and 183 healthy controls. The reliability and
internal consistency of the measure were assessed through test-retest methods
using Cronbach's coefficient alpha and intra-class correlation coefficients
(ICCs). For validation of the measure, factorial validity, concurrent validity
using the Japanese version of PedsQL 4.0 Generic Core Scales (PedsQL-J), and
discriminant validity using comparisons between children with cancer and healthy
controls were investigated. RESULTS: Of the 46 items in the original version, 44
items were determined to comprise the Japanese version of the MMQL-AF. Cronbach's
coefficient alphas for each subscale were high ranging from 0.83 to 0.89. Test
retest reliability ranged between ICC 0.79 to 0.96. Investigation of concurrent
validity using the PedsQL-J demonstrated strong correlations in physical
functions and moderate correlations for other factors. A significant difference
was observed between children with cancer and healthy controls. CONCLUSIONS:
Thus, the Japanese version of the MMQL-AF served as a self-evaluation
questionnaire that allowed for practical, comprehensive, and multidimensional
measurement of HRQOL specific to childhood cancer survivors.
PMID- 25124111
TI - Electrochemical synthesis on nanoparticle chains to couple semiconducting rods:
coulomb blockade modulation using photoexcitation.
AB - Hybrid nanostructures are made by coupling a room temperature coulomb blockade
device with photoexcitable nano-rods. Direct electrochemical synthesis on
nanoparticle chain arrays leads to the formation of semiconducting rods that are
in direct contact with the nanoparticles and also spatial confined by them. This
direct interfacing leads to mutual intermodulation between the two systems.
PMID- 25124112
TI - Synthesis and biological evaluation of novel thiadiazole amides as potent Cdc25B
and PTP1B inhibitors.
AB - A series of novel thiadiazole amide derivatives have been synthesized and
evaluated for inhibitory activities against Cdc25B and PTP1B. Most of them showed
inhibitory activities against Cdc25B (IC50=1.18-8.01 MUg/mL) and PTP1B (IC50=0.85
8.75 MUg/mL), respectively. Moreover, compounds 5b and 4l were most potent with
IC50 values of 1.18 and 0.85 MUg/mL for Cdc25B and PTP1B, respectively, compared
with reference drugs Na3VO4 (IC50=0.93 MUg/mL) and oleanolic acid (IC50=0.85
MUg/mL). The results of selectivity experiments showed that the target compounds
were selective inhibitors against PTP1B and Cdc25B. Enzyme kinetic experiments
demonstrated that compound 5k was a specific inhibitor with the typical
characteristics of a mixed inhibitor.
PMID- 25124113
TI - Cytotoxic activity of butane type of 1,7-seco-2,7'-cyclolignanes and apoptosis
induction by Caspase 9 and 3.
AB - All stereoisomers of methoxybutane and fluorobutane type of 1,7-seco-2,7'
cyclolignane were synthesized and cytotoxic activities of these compounds were
compared with those of all stereoisomers of butane and butanol type compounds.
Both enantiomers of butane type secocyclolignane showed higher cytotoxic activity
(IC50=16-20 MUM) than methoxy type compounds, whereas none was observed for all
the stereoisomers of butanol type secocyclolignane, however, (-)-Kadangustin J
showed stereospecific cytotoxic activity (IC50=47-67 MUM). Since (R)-9'-fluoro
derivative 23 was most potent (IC50=19 MUM) among the corresponding fluoro
stereoisomers, (R)-9'-alkyl derivatives were synthesized, hydrophobic 9'-heptyl
derivative 27 showing highest activity (IC50=3.7 MUM against HL-60, IC50=3.1 MUM
against HeLa) in this experiment. Apoptosis induction caused by Caspase 3 and 9
for (R)-9'-heptyl derivative 27 was observed in the research on the mechanism. A
degradation of DNA into small fragments was also shown by DNA ladder assay.
PMID- 25124114
TI - Phorbaketals L-N, cytotoxic sesterterpenoids isolated from the marine sponge of
the genus Phorbas.
AB - Three new sesterterpenoids, phorbaketals L-N (1-3), were isolated from a marine
sponge of the genus Phorbas and their complete structures were elucidated via
analysis of HRFABMS and NMR spectroscopic data. Phorbaketal N (3) showed potent
cytotoxicity against human pancreas cancer cells (IC50=11.4 MUM).
PMID- 25124116
TI - 4-Substituted quinazoline derivatives as novel EphA2 receptor tyrosine kinase
inhibitors.
AB - Erythropoietin-producing hepatocellular receptor tyrosine kinase subtype A2
(EphA2) is an attractive therapeutic target for suppressing tumor progression. In
our efforts to discover novel small molecules to inhibit EphA2, a class of
compound based on 4-substituted quinazoline containing 7-(morpholin-2-ylmethoxy)
group was identified as a novel hit by high throughput screening campaign.
Structural modification of parent quinazoline scaffolds by introducing
substituents on aniline displayed potent inhibitory activities toward EphA2.
PMID- 25124115
TI - Design, synthesis and evaluation of benzoisothiazolones as selective inhibitors
of PHOSPHO1.
AB - We report the discovery and characterization of a series of benzoisothiazolone
inhibitors of PHOSPHO1, a newly identified soluble phosphatase implicated in
skeletal mineralization and soft tissue ossification abnormalities. High
throughput screening (HTS) of a small molecule library led to the identification
of benzoisothiazolones as potent and selective inhibitors of PHOSPHO1. Critical
structural requirements for activity were determined, and the compounds were
subsequently derivatized and measured for in vitro activity and ADME parameters
including metabolic stability and permeability. On the basis of its overall
profile the benzoisothiazolone analogue 2q was selected as MLPCN probe ML086.
PMID- 25124118
TI - Affective and cognitive determinants of women's sexual response to erotica.
AB - INTRODUCTION: The specific cognitive-affective mechanisms involved in the
activation and regulation of the subjective and genital components of sexual
arousal are not fully understood yet. AIM: The aim of the present study was to
investigate the contribution of self-reported thoughts and affect to the
prediction of women's subjective and genital responses to erotica. METHODS:
Twenty-eight sexually functional women (mean age = 32, SD = 6.29) were presented
with sexually explicit and nonexplicit romantic films. Genital responses,
subjective sexual arousal, state affect, and self-reported thoughts were
assessed. MAIN OUTCOME MEASURES: Vaginal pulse amplitude was measured using a
vaginal photoplethysmograph. Subjective sexual arousal, thoughts, and affective
responses were assessed through self-report scales. RESULTS: Correlations between
subjective and physiological sexual arousal were low (r = -0.05, P > 0.05). Self
reported thoughts and affect were significant predictors of subjective sexual
arousal. The strongest single predictor of subjective arousal was sexual arousal
thoughts (e.g., "I'm getting excited") (beta = 0.63, P < 0.01). None of the
cognitive or affective variables predicted women's genital responses.
CONCLUSIONS: Overall, results support the role of cognitive (self-reported
thoughts) and affective dimensions in women's subjective sexual arousal to
erotica and, consistent with previous findings, suggest that subjective and
physiological sexual arousal may be impacted by different processes.
PMID- 25124117
TI - Complotype affects the extent of down-regulation by Factor I of the C3b feedback
cycle in vitro.
AB - Sera from a large panel of normal subjects were typed for three common
polymorphisms, one in C3 (R102G) and two in Factor H (V62I and Y402H), that
influence predisposition to age-related macular degeneration and to some forms of
kidney disease. Three groups of sera were tested; those that were homozygous for
the three risk alleles; those that were heterozygous for all three; and those
homozygous for the low-risk alleles. These groups vary in their response to the
addition of exogenous Factor I when the alternative complement pathway is
activated by zymosan. Both the reduction in the maximum amount of iC3b formed and
the rate at which the iC3b is converted to C3dg are affected. For both reactions
the at-risk complotype requires higher doses of Factor I to produce similar down
regulation. Because iC3b reacting with the complement receptor CR3 is a major
mechanism by which complement activation gives rise to inflammation, the
breakdown of iC3b to C3dg can be seen to have major significance for reducing
complement-induced inflammation. These findings demonstrate for the first time
that sera from subjects with different complement alleles behave as predicted in
an in-vitro assay of the down-regulation of the alternative complement pathway by
increasing the concentration of Factor I. These results support the hypothesis
that exogenous Factor I may be a valuable therapeutic aid for down-regulating
hyperactivity of the C3b feedback cycle, thereby providing a treatment for age
related macular degeneration and other inflammatory diseases of later life.
PMID- 25124119
TI - An open trial of group metacognitive therapy for depression in Norway.
AB - BACKGROUND: Preliminary data support the implementation of individual
metacognitive therapy (MCT) for depression. Given the focus of MCT on
transpersonal processes, we hypothesized that this treatment should translate
well to a group format. In this study, the effects and feasibility associated
with group MCT for depression are reported. METHODS: Eleven patients who were
consecutively referred by general practitioners to a specialist psychiatric
practice in Norway participated in an open trial of the effects and feasibility
associated with group MCT for depression. All of the patients met the DSM-IV
criteria for major depressive disorder (MDD) and were monitored in a baseline
period before attending 90-min weekly treatment sessions of group MCT for 10
weeks. The primary symptom outcome measure was severity of depression whilst
secondary outcome measures included levels of anxiety, rumination and
metacognitive beliefs. We also assessed recovery rates and changes in comorbid
Axis I and Axis II diagnoses. RESULTS: Large clinically significant improvements
across all measures were detected at post-treatment and these were maintained at
follow-up. Based on objectively defined recovery criteria, all patients were
classified as recovered at post-treatment and 91% at 6 months follow-up. The
intervention was also associated with significant reductions in comorbid
diagnoses. CONCLUSIONS: These preliminary data indicate that group MCT in the
treatment of depression is effective, well accepted and it extends clinical
application of MCT for depression to group formats as a potential cost-effective
intervention.
PMID- 25124120
TI - Methanol steam reforming promoted by molten salt-modified platinum on alumina
catalysts.
AB - We herein describe a straight forward procedure to increase the performance of
platinum-on-alumina catalysts in methanol steam reforming by applying an alkali
hydroxide coating according to the "solid catalyst with ionic liquid layer"
(SCILL) approach. We demonstrate by diffuse reflectance infrared Fourier
transform spectroscopy (DRIFTS) and temperature-programmed desorption (TPD)
studies that potassium doping plays an important role in the catalyst activation.
Moreover, the hygroscopic nature and the basicity of the salt modification
contribute to the considerable enhancement in catalytic performance. During
reaction, a partly liquid film of alkali hydroxides/carbonates forms on the
catalyst/alumina surface, thus significantly enhancing the availability of water
at the catalytically active sites. Too high catalyst pore fillings with salt
introduce a considerable mass transfer barrier into the system as indicated by
kinetic studies. Thus, the optimum interplay between beneficial catalyst
modification and detrimental mass transfer effects had to be identified and was
found on the applied platinum-on-alumina catalyst at KOH loadings around 7.5
mass%.
PMID- 25124121
TI - Subtypes of non-suicidal self-injury based on childhood adversity.
AB - The aim of this study was to examine the latent clusters in non-suicidal self
injury (NSSI) based on childhood adversity. Data were derived from Waves I (2001
2002) and II (2004-2005) of the National Epidemiologic Survey on Alcohol and
Related Conditions, a nationally representative sample of U.S. adults.
Individuals engaging in NSSI (N = 672) comprised the analytic sample. Latent
class statistical analysis was undertaken to elucidate the latent structure of
NSSI based on child experiences of physical and sexual abuse, neglect, and family
violence. Four-classes of respondents were identified vis-a-vis childhood
adversities. A low abuse/neglect class (35.7% of respondents, 91.1% male)
demonstrated less mental health and substance use comorbidity and antisocial
behavior. A sexual abuse class (43.1% of respondents, 98.6% female) evinced
somewhat lower levels of antisocial behavior than the other classes but similarly
high levels of mental health disorder and a non-sexual abuse/neglect class (8.3%
of respondents, 91.5% male) characterized by varied and intensive forms of
antisocial and externalizing behaviors. Finally, a severe high
abuse/neglect/family violence class (12.95% of respondents, 100% female)
demonstrated high levels of clinical psychiatric and personality disorders. The
current project is a nationally representative study of NSSI latent clusters and
extends and validates the existence of NSSI subtypes revealed by prior research.
PMID- 25124122
TI - [Medical consultation concerning the productive aged population and air pollution
in Bogota: 2008 and 2010].
AB - OBJECTIVE: Exploring the relationship of current air pollution levels in Bogota
for breathable particulate matter (<10 microns) PM10 and medical consultation
during productive age (18 to 65 years old). METHODS: Data regarding Bogota's air
quality monitoring network for 2008 to 2010 was reviewed, specifically PM10
levels and diagnosis arising from medical consultations in Bogota's public
hospitals during this time. RESULTS: According to the air quality monitoring
network's results there was an 8 MUg/m3 decrease in annual average PM10 from 2008
to 2010 (11.9 %) and, although consultations on grounds relating to air pollution
increased by 58.7 % from 2008 to 2010, an overall 1.2 % decrease was observed
when comparing this to the total of medical consultations each year. CONCLUSIONS:
A significant percentage of medical attention provided in Bogota may be related
to its air quality; the set of control policies developed in Bogota for some time
now have led to a significant reduction in PM10 levels.
PMID- 25124123
TI - [Air pollution and respiratory illness in children aged less than 5 years-old in
Bogota, 2007].
AB - OBJECTIVES: Determining the relationship between indoor and outdoor air pollution
caused by particulate matter PM10 and respiratory symptoms in children aged
younger than 5 years-old in three locations in Bogota. METHODS: This was a cohort
study, involving 315 children in kindergartens located in the area of greatest
exposure to PM10, and 304 in kindergartens located in an area of less exposure.
The cohort was followed-up for 19 weeks considering respiratory symptoms.
Particulate matter was intramurally and extramurally measured in the
kindergartens. Prevalence and association between variables were determined.
RESULTS: There was a difference regarding average intramural PM between higher
and lower exposure (85.6 ug/m3cf 61.8 g/m3; p<0.05); 74.3 % of the children had
suffered wheezing during the last year, difference between greater and lesser
exposure being 79.6 % cf 69.0 % (p<0.05). Wheezing and coughing were associated
with greater exposure to PM10 (RR 1.39 and 1.30). Factors associated with
respiratory symptoms concerned passive smoking, having a history of low birth
weight, a history of wheezing, a child's kindergarten or home being within 100
meters of (industrial) chimneys, high traffic flow routes, roads in disrepair and
bed-sharing. DISCUSSION: A child aged less than 5 years-old exposed to PM10 had a
1.7 times higher risk of truancy due to acute respiratory illness; a decrease in
PM10 reduced such truancy by 41.1 %.
PMID- 25124124
TI - [Constructing a tool for certifying handicap / disability in Colombia].
AB - OBJECTIVE: Describing how a tool was created/constructed for certifying Colombian
people's disability status. METHOD: This was a descriptive study involving a five
phase, multi-method design. It sought to identify needs, background, categories
and procedures from differing view points, using participatory methodology, for
identifying and certifying disabled people in Colombia. RESULTS: The study led to
an international classification of functioning, disability and health (ICF)-based
certification tool which can be used by a multi-professional team in healthcare
institution settings to guarantee access to benefits approved by Colombian
disability law. CONCLUSIONS: Certification (even when voluntary) can be the key
to enjoying all the benefits designed for Colombian people suffering disability;
such people are not the subjects of mercy and compassion anymore. Certification
seeks to identify people suffering disabilities as holders of rights under
Colombian law, as clear evidence of Colombian state commitment to ensuring an
inclusive society.
PMID- 25124125
TI - [Inequality regarding maternal mortality in Colombian departments in 2000-2001,
2005-2006 and 2008-2009].
AB - OBJECTIVE: Describing inequality regarding maternal mortality in Colombia for
2000-2001, 2005-2006 and 2008-2009. METHODS: This was an ecological study. The
maternal mortality rate (MMR) was estimated, adjusted for maternal age, Colombian
department and causes of maternal mortality. The main causes of mortality were
described for 2000-2001, 2005-2006 and 2008-2009. The excess of risk of maternal
death in Colombia was calculated regarding the best external referent using the
attributable fraction (AF). The AF was correlated with the indicator of
unsatisfied basic needs (UBN) by department. RESULTS: The highest MMR in Colombia
was between 81 and 161 per 100,000 live births and the lowest between 3 and 5;
the lowest MMR in the world was between 2 and 4 per 100,000 live births for the
same periods. The main causes of maternal mortality in Colombia were hypertension
during pregnancy, unclassified obstetric conditions and complications when giving
birth. An excess of risk of maternal mortality in Colombia was found (on average
86 %) when compared to an external referent. A correlation was found between AF
and UBN. CONCLUSIONS: Great inequality was found regarding maternal mortality in
Colombia and when comparing Colombia to developed countries. Inequality regarding
maternal mortality persists in spite of advances having been made regarding
reform of the healthcare system, thereby suggesting that this has not been
effective in reducing maternal mortality and its inequalities.
PMID- 25124126
TI - [Socio-demographic and healthcare conditions regarding maternal self
sufficiency/effectiveness concerning preventing diarrhea during childhood].
AB - OBJECTIVE: Investigating the correlation between socio-demographic conditions,
health and maternal self-efficacy to prevent childhood diarrhoea. METHODS: This
was a quantitative cross-sectional study which was conducted in Fortaleza, in
north-eastern Brazil; it involved 448 mothers of children aged less than 5 years
old. Data was collected through interviews held in the family healthcare centres
using an in-house maternal self-efficacy for childhood diarrhoea prevention scale
and a form for collecting information about the mothers' socio-demographic
profile. RESULTS: The self-sufficiency/effectiveness in preventing diarrhoea
during childhood interview data revealed a statistically significant association
with maternal age (p=0.018), per capita income (p=0.023), type of housing
(p=0.032), garbage disposal from the dwelling (p=0.000), origin of the water
drunk by the children (p=0.002), type of sanitary installation (p=0.001) and its
location (p=0.023), type of drainage (p=0.046) and the resources used by the
mothers regarding their personal hygiene (p=0.002). CONCLUSIONS: Healthcare staff
should advance strategies for improving self-sufficiency/effectiveness regarding
maternal care for children, especially regarding preventative measures concerning
diarrhoea during childhood.
PMID- 25124127
TI - [IMCI and the maternal practice of African descendants' living on the Colombian
Caribbean coast regarding the common cold and diarrhea].
AB - OBJECTIVE: Evaluating maternal practice regarding diarrhoea and the common cold.
METHOD: This was a cross-sectional descriptive study which was conducted on the
island of Baru, near Cartagena, Colombia. It involved 127 mothers of African
descent and their 138 children aged less than 5 years of age; convenience
sampling was used. The Integrated Management of Childhood Illness (IMCI)
instrument was used for the survey during a one-day healthcare session. The
prevalence of diarrhoea and the common cold during the 7 days immediately before
the survey were estimated, as were maternal practice regarding these and the
occurrence of other risks and protective factors; a history of breastfeeding,
complementary feeding and vaccination was compiled. Descriptive statistics were
used and the chi2 test was used for ascertaining the significance of the
relationships between variables. RESULTS: Diarrhoea prevalence was 71.7 % (64-79
95 % CI), this being lower for girls aged 2 months to 5 years-old (p = 0,02) and
common cold prevalence was 99.2 % (97-100 95 % CI), this being higher in girls
aged older than 2 months (p=0.004). 86.9 % (81-92 95 % CI) of the mothers did not
know how to identify warning signs for these diseases, 84.9 % (78-90 95 % CI) of
the practices were inadequate and 73.3% of the mothers took their children to a
doctor as their first line medical practice (p=0.05). CONCLUSIONS: Efforts must
be increased regarding the implementation of the IMCI strategy in vulnerable
communities, through effective channels of communication and innovative ways to
reduce child morbidity and mortality indices, thereby promoting the island's
social development.
PMID- 25124129
TI - [An analysis of low birth weight in Colombia, 2005-2009].
AB - OBJECTIVE: Analysing Colombia's low birth weight pattern over a five-year period
(2005 to 2009) and identifying the determinants and risk factors associated with
such low birth weight rate. METHODS: This was a retrospective descriptive study
which used the information contained in live birth certificates. Ratios were
calculated for each selected variable and a multivariate logistic regression
model was used for determining the associated predictors. RESULTS: The low birth
weight rate was 8.6 % on average, this being higher in urban areas (8.9 %) and in
the new born of mothers affiliated to the Colombian social security health
insurance system's contributory regime (9.2 %). The low birth weight rate was
higher in mothers lacking education (9.7 %) and those having a university or
higher level of education (9.1 %). The predictors associated with the full-term
newborn were caesarean delivery (OR 1.49), being female (OR 1.47), having
attended less than four prenatal visits (OR 1.32), those being pregnant for the
first time (OR 1.28) and being a single mother (OR 1.17). CONCLUSIONS: The low
birth weight rate has increased each year and is linked to factors such as type
of delivery, a child's gender, the number of prenatal visits, the number of
previous live births, marital status, educational level and maternal age. These
factors should form the target for Colombian public health policy and
intervention.
PMID- 25124128
TI - [Nutritional state associated with social determinants in Arhuaco children aged
less than 5 years-old].
AB - OBJECTIVES: Misinformation concerning indigenous communities is an obstacle to
ascertaining their healthcare status; however, the role of malnutrition
concerning their morbidity and mortality is unquestionable. The aim of this study
was to ascertain food security levels and identify social determinants and their
association with the nutritional status of children aged less than five years
old. METHODOLOGY: This was a cross-sectional, analytical study of an Arhuaco
population which used non-probability sampling for convenience. Anthropometry
included analyzing weight, length and head circumference based on WHO 2006
references for nutritional diagnosis. Social determinants were obtained using an
instrument adapted from the Pan American Health Organization (PAHO). Relevant
ethical considerations were taken into account. RESULTS: 169 children were
evaluated and 132 surveys conducted. Growth delay regarding size was less
frequent in children aged less than 6 months (p=0.03)and acute malnutrition was
higher in those who went to see a traditional doctor first (p=0.01) and whose
mothers had no formal schooling (p=0.05); the latter association was also found
regarding obesity (p=0.00) and in those having risk factors concerning
neurodevelopment too (p=0.00). Nutritional transition was higher in males
(p=0.03), in children lacking complete vaccination (p=0.03) and in those whose
mothers had 4 or fewer children (p=0.00). CONCLUSIONS: Strategies aimed at taking
action regarding acute malnutrition and being overweight must be formulated,
plans for monitoring growth in this population must be promoted and communication
between traditional and Western medicine must be optimized, involving mothers as
the main actors.
PMID- 25124130
TI - Effect of biomass smoke on chronic obstructive pulmonary disease in rural
localities of Colombia.
AB - OBJECTIVES: The aim of this study was to assess the differences associated to the
change of biofuel used to cook as a way to estimate the proportion of respiratory
abnormalities of respiratory function associated to biomass exposure. METHODS: A
cross-sectional study was designed to evaluate the respiratory function through
spirometry in subjects cooking with biomass or natural gas. All patients were
evaluated by a general physician and a pulmonologist. We compared the prevalence
of spirometry abnormalities across those cooking with natural gas versus those
cooking with biofuel. A multivariable logistic regression and multiple linear
regression were used to adjust differences by potential confounding factors.
RESULTS: 203 subjects were studied. There was a significant increase in the
prevalence of severe obstructive pattern (OR 5.50; 95 % CI 1.17-25.79) in
subjects who cook with biomass compared with natural gas users. Values of forced
expired volume in one second (FEV1) and forced vital capacity (FVC) were
statistically lower among those cooking with biomass. The prevalence of
respiratory morbidity and symptoms were not statistically significant between
both groups. CONCLUSIONS: These findings suggest that replacing biomass fuel by
natural gas may be an important public health intervention in Colombia, because
it can reduce the prevalence of abnormal patterns of pulmonary function.
PMID- 25124131
TI - [Muscular strength training does not increase human adults' arterial stiffness or
improve body toning].
AB - OBJECT: Determining the influence of three weekly strength training (ST)
sessions, over a ten-week period, on arterial stiffness (AS) and taking the
associated anthropometric measurements. METHODS: This was a before-and-after
intervention trial, involving a sample of 17 individuals. Participants were
adults from both genders aged 18 and 40 years-old who had been sedentary for at
least three months previously. Anthropometric measurements were taken, together
with pulse wave velocity (PWV) before and immediately after the experimental
sessions. RESULTS: Independent variables (age and gender) were considered for
determining their influence on final PWV and anthropometric measurements.
Comparing initial PWV (mean=9.00) with final PWV (mean=9.00) for subjects
involved in the proposed ST revealed no significant difference between them
(p=0.469). Regarding anthropometric measurement, individuals' body fat (p<0.001)
and body fat mass percentages (p<0.001) became significantly reduced, accompanied
by an increase in lean mass (p<0.001). However, no changes were recorded
regarding waist-to-hip ratio (WHR) (p= 0.777), body mass (p=0.226) or body mass
index (BMI) (p =0.212). CONCLUSION: This study's findings suggested that the
proposed ST did not increase AS. Devotees of such type of training may therefore
safely enjoy all its benefits without risk to the cardiovascular system. Further
controlled and randomized research is needed to confirm these results.
PMID- 25124132
TI - [An occupational assessment of disabled people in Colombia: an exploratory
analysis of ongoing practice].
AB - OBJECTIVE: This paper analyses a study of the current state of occupational
assessment of disabled people; it took place in 14 public and private
institutions involved in promoting the inclusion of this population in the
workforce. The study was aimed at providing definitions, demonstrating the
pertinent processes, instruments, professionals, stages of the process and
support involved in helping disabled people to become included in the workforce.
METHODOLOGY: The study involved a group of experts adopting a methodology which
designed, implemented and analysed a data collection instrument seeking
qualitative and quantitative data concerning target populations, assessment
purposes, the instruments used, timing and other relevant factors for programmes
aimed at disabled people becoming included in the workforce. The 14 Colombian
institutions having most experience regarding this topic participated in the
study (the oldest having 40 years' experience and the most recent 8 years in this
field). RESULTS: The results indicated widespread heterogeneity regarding the
occupational assessment components explored. It was found that the objectives
proposed for each process differed, depending on each institution's philosophy
and structure, the model's characteristics and those of the intraprofessional
teams. They also highlighted the broad range of instruments and timing (i.e. 1 to
180 days) of sub-processes used as tools for occupational assessment (of the
disabled). CONCLUSIONS: These findings constitute a foundation justifying the
compilation of a Manual for the Occupational Assessment of Disabled People in
Colombia, recognising accumulated cognitive, social and professional capital
(i.e. established tradition in this field).
PMID- 25124134
TI - [Modelling respiratory syncytial virus (RSV) transmission children aged less than
five years-old].
AB - OBJECTIVES: Studying respiratory syncytial virus (RSV) transmission dynamics in a
population of children aged less than 5 years-old using deterministic models.
METHOD: A deterministic susceptible-infected-removed(SIR) mathematical model with
seasonal forcing was used for the simulation. RESULTS: A mathematical
epidemiological model (SIRS) with seasonal forcing was proposed which explained
RSV dynamics between 2005 and 2010 in a population of children aged less than
five years-old in Bogota. CONCLUSIONS: The mathematical model (SIRS) with
seasonal forcing explained the cyclical pattern of cases of children aged less
than five years old infected with RSV in Bogota, Colombia during the target
period.
PMID- 25124133
TI - [Knowledge about dengue and cardio-cerebrovascular disease in a town in
Colombia].
AB - OBJECTIVE: This study aimed at describing a low-income population's knowledge and
perception concerning dengue and cardio-cerebrovascular disease in a town in
Colombia. METHOD: The study involved qualitative research; data from 16 semi
structured individual and 3 focus groups was collected through questionnaires
addressing 3 low-income sectors and then interpreted. Deductive categorisation of
data was based on the questions and inductive analysis to establish such
population's knowledge for studying their perceptions regarding dengue and cardio
cerebrovascular disease. RESULTS: It was evident that the target population knew
about the agents, the forms of acquiring such diseases, the risk factors and
action to be taken for preventing and controlling both diseases; however, such
knowledge did not represent (i.e. had not led to) changes in their daily practice
or lifestyles. CONCLUSIONS: Local health centre actions needs to be supported by
theory or models and must go beyond single interventions based essentially on the
transmission of information.
PMID- 25124135
TI - Pain and inflammation in hidradenitis suppurativa correspond to morphological
changes identified by high-frequency ultrasound.
AB - BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory skin disease with a
chronic intermittent course. The current classification systems used to
categorize disease severity provide limited insight into the degree of
inflammation and pain, which are key symptoms of the disease. OBJECTIVE: We
sought to investigate the correlation and validity of simple patient- and
investigator-assessed items related to inflammation with morphological changes
identified by high-frequency ultrasound in HS. METHODS: Twenty patients with the
clinical diagnosis of HS were enrolled in this study. All patients underwent
clinical examinations during which one representative inflammatory nodule was
selected in each patient based on the anamnestic information, patient experience
and clinical presentation. Tenderness and flare activity of the representative
nodule were graded by the patients and erythema by the investigator.
Subsequently, all patients underwent high-resolution ultrasound scanning of their
representative nodule. RESULTS: We found significant associations between the
size of the representative nodule (the diameter in the transverse plane) and
patient assessments of flare activity and tenderness. Moreover, we found a marked
association between the size of the nodules and investigator assessment of
erythema. CONCLUSION: Patient assessments of flare activity and pain, and
investigator assessment of erythema are strongly associated with morphological
changes identified using ultrasound, suggesting that these patient- and
investigator-assessed items might be strong indicators of the degree of present
inflammation in HS.
PMID- 25124136
TI - Comparison of the microbiological quality of environmentally friendly and
conventionally grown vegetables sold at retail markets in Korea.
AB - Fresh produce is usually eaten raw without cooking or heating, which may increase
the probability of foodborne infection. The microbiological quality of 11 types
of fresh, raw vegetables (romaine lettuce, sesame leaves, crown daisy, garlic
chives, iceberg lettuce, cabbage, broccoli, leek, chili pepper, capsicum, and
zucchini) purchased at retail markets in Iksan, Korea as affected by cultivation
method (environmentally friendly vegetables [organic, pesticide-free, and low
pesticide vegetables] and conventionally grown vegetables) and harvest season was
determined. Escherichia coli O157:H7 and Salmonella were not detected in all
samples of vegetables tested. Aerobic mesophiles (>6 log cfu/g) were detected in
environmentally friendly romaine lettuce and crown daisy and environmentally
friendly and conventionally grown garlic chives, which also contained coliforms
(>3 log cfu/g). Sesame leaf and crown daisy (regardless of cultivation method),
as well as conventionally grown romaine lettuce and leek, contained >1 log cfu/g
of E. coli. The overall microbiological quality of environmentally friendly and
conventionally grown vegetables was not significantly different (P > 0.05).
However, there were seasonal effects on populations of coliforms and generic E.
coli on vegetables. The greatest numbers of microorganisms were isolated from
environmentally friendly or conventionally grown vegetables purchased in winter.
The vegetables, regardless of cultivation method or season, should be subjected
to appropriate antimicrobial treatment to enhance their microbial safety.
PMID- 25124137
TI - Optimizing oxygen delivery in the critically ill: the utility of lactate and
central venous oxygen saturation (ScvO2) as a roadmap of resuscitation in shock.
AB - BACKGROUND: Resuscitation of any critically ill patient is aimed at restoration
of oxygen delivery to maintain aerobic metabolism. Thus, "endpoints" of
resuscitation have been sought after as a measure of evaluating the adequacy of
resuscitation. This review article describes the most commonly used endpoints,
central venous oxygen saturation (ScvO2) and lactate, and provides a clinically
useful paradigm for utilizing these endpoints during resuscitation of critically
ill patients in the emergency department (ED). OBJECTIVE: This review article
will summarize the pathophysiology of cellular shock, describe the available
research regarding lactate and ScvO2, and provide an approach to utilizing these
endpoints during resuscitation in the ED. DISCUSSION: ScvO2 and lactate each have
been shown to be useful for the assessment of shock, yet each has inherent
limitations. When used together, ScvO2 and lactate provide the emergency
physician with a glimpse of the underlying pathophysiologic state, allowing
targeted therapy to restore oxygen delivery. CONCLUSION: ScvO2 and lactate are
useful endpoints of resuscitation, and when used together, provide a metabolic
framework for guiding targeted therapy for critically ill patients in the ED with
shock.
PMID- 25124138
TI - Entrustable professional activities: making sense of the emergency medicine
milestones.
AB - BACKGROUND: The Next Accreditation System (NAS) is being implemented by the
Accreditation Council for Graduate Medical Education with seven specialties,
including Emergency Medicine (EM), which began in July 2013. The NAS represents a
more structured method of accreditation, with dependence on outcomes and less
emphasis on educational process. A key component of the NAS is the individual
resident semiannual reporting of the Milestone proficiency levels for all sub
competencies, which are more specific areas of domain for the general
competencies. All specialties are struggling to some extent with developing
assessment mechanisms for the Milestones. At the heart of this struggle is the
conceptualization of the Milestones themselves-descriptors of the individual. In
practice, faculty assess clinical care provided to the patient by the resident.
This creates difficulty for faculty to assign a resident to a specific sub
competency proficiency level when their focus has been on assessment of clinical
care. OBJECTIVES: The objectives of this article include the discussion of
whether Entrustable Professional Activities (EPAs) could be defined and linked to
milestones in a way that, once implemented, could inform Clinical Competency
Committees of the Milestone proficiency reporting. DISCUSSION: EPAs are units of
professional work, or clinical care that may help translate aspects of clinical
care into Milestone proficiencies. This article explores EPAs in depth, and
discusses how EPAs may be used within EM as one method of assigning proficiency
levels to residents. CONCLUSIONS: EPAs may be a useful tool to inform Milestone
proficiency placement of residents. Because EPAs are based on clinical
descriptions rather than individual physician descriptions, there may be less
faculty development needed for Milestone sub-competency assessment.
PMID- 25124139
TI - [Sedation in endoscopic procedures performed by intensivists].
PMID- 25124140
TI - HIV testing preferences in Tanzania: a qualitative exploration of the importance
of confidentiality, accessibility, and quality of service.
AB - BACKGROUND: HIV counseling and testing (HCT), an effective preventive strategy
and an entry point for care, remains under-utilized in Tanzania. Limited uptake
of HCT, despite the widespread availability of varied testing options, suggests
that existing options may not align well with population preferences for testing.
METHODS: Between October and December 2011, we conducted an exploratory study in
the Kilimanjaro Region to develop a conceptual framework for understanding which
characteristics of HIV testing are associated with preferences for testing. Forty
individuals (55% women, 53% never having tested) participated in in-depth
interviews and focus groups to identify factors that influence whether and where
people test for HIV. RESULTS: A variety of discrete characteristics of testing
venues, test providers, and testing procedures (e.g. distance to testing,
counselor experience, type of HIV test, and availability of antiretroviral
therapy) mapped conceptually to three domains: confidentiality of testing and
test results, quality of HCT, and accessibility and availability of ancillary
services. We noted heterogeneous preferences and demonstrate that while some test
characteristics overlap and reinforce across multiple domains, others demand
clients to make trade-offs between domains. CONCLUSION: Testing decisions appear
to be influenced by an array of often inter-linked factors across multiple
domains, including quality, confidentiality, and accessibility; perceptions of
these factors varied greatly across participants and across available testing
options. HCT interventions that jointly target barriers spanning the three
domains have the potential to increase uptake of HIV testing and deserve further
exploration.
PMID- 25124142
TI - Uranium incorporation into aluminum-substituted ferrihydrite during iron(ii)
induced transformation.
AB - Uranium retention processes (adsorption, precipitation, and incorporation into
host minerals) exert strong controls on U mobility in the environment, and
understanding U retention is therefore crucial for predicting the migration of U
within surface and groundwater. Uranium can be incorporated into Fe (hydr)oxides
during Fe(ii)-induced transformation of ferrihydrite to goethite. However,
ferrihydrite seldom exists as a pure phase within soils or sediments, and
structural impurities such as Al alter its reactivity. The presence of Al in
ferrihydrite, for example, decreases the rate of transformation to goethite, and
thus may impact the retention pathway, or extent of retention, of U. Here, we
investigate the extent and pathways of U(vi) retention on Al-ferrihydrite during
Fe(ii)-induced transformation. Ferrihydrite containing 0%, 1%, 5%, 10%, and 20%
Al was reacted with 10 MUM U and 300 MUM Fe(ii) in the presence of 0 mM and 4 mM
Ca(2+) and 3.8 mM carbonate at pH 7.0. Solid reaction products were characterized
using U L3-edge EXAFS spectroscopy to differentiate between adsorbed U and U
incorporated into the goethite lattice. Uranium incorporation into Al
ferrihydrite declined from ~70% of solid-phase U at 0% and 1% Al to ~30% of solid
phase U at 20% Al content. The decrease in U incorporation with increasing Al
concentration was due to two main factors: (1) decreased transformation of
ferrihydrite to goethite; and, (2) a decrease of the goethite lattice with
increasing Al, making the lattice less compatible with large U atoms. However,
uranium incorporation can occur even with an Al-substituted ferrihydrite
precursor in the presence or absence of Ca(2+). The process of U incorporation
into Al-goethite may therefore be a potential long-term sink of U in subsurface
environments where Al-substituted iron oxides are common, albeit at lower levels
of incorporation with increasing Al content.
PMID- 25124141
TI - Follow-up on pediatric patients with bronchiolitis obliterans treated with
corticosteroid pulse therapy.
AB - BACKGROUND: Bronchiolitis obliterans (BO) is a rare but severe disease in
children. Currently, there is no consensus on the treatment for BO with respect
to the systemic use of corticosteroids. Here we report on the follow-up of
children with a diagnosis of BO who were treated with corticosteroid pulse
therapy. METHODS: Forty patients fulfilling the BO diagnosis criteria were
treated with methylprednisolone pulse therapy in monthly cycles until clinical
improvement. After the pulse therapy began, we analyzed the clinical and
laboratory data at intervals. Statistical analyses were performed using non
parametric tests to compare repeated measures (Friedman, Wilcoxon) or paired
nominal data (McNemar) (alpha = 5%). RESULTS: The frequency of wheezing
exacerbations and hospitalizations was reduced (p = 0.0042 and p < 0.0001,
respectively) and oxygen saturation improved (p = 0.0002) in the pulse therapy
treated patients. Prolonged oral corticosteroid therapy was discontinued in 83%
of these patients. The mean Z-score length for age improved from -1.08 to -0.63,
and the mean Z-score weight for age improved from -0.91 to -0.59. The adverse
effects during the infusion were temporary and none were serious. CONCLUSIONS:
Our data suggest that pulse corticotherapy could be a safe alternative to
prolonged systemic oral corticotherapy in children with BO, thus minimizing the
adverse effects of the oral therapy. New prospective controlled studies are
required to confirm this proposition.
PMID- 25124143
TI - The macropod type 2 interferon gene shares important regulatory and functionally
relevant regions with eutherian IFN-gamma.
AB - Interferon-gamma (IFN-gamma) is an important immune regulatory molecule that
plays a significant role in internal and external modulation of the mammalian
immune response to intracellular pathogens. Herein, we report the 492 nt
expressed sequence for the coding domain of IFN-gamma from the immune tissues of
two Australian macropod marsupial species: the tammar wallaby (Macropus eugenii)
and the vulnerable rufous hare-wallaby (Lagorchestes hirsutus). Both 5' and 3'
untranslated regions and the coding domain of M. eugenii IFN-gamma revealed the
presence of motifs responsible for transcriptional regulation, mRNA regulation,
post-translational modifications, and receptor binding in other mammals. Since
diagnostic kits for mycobacterial disease commonly rely on the assessment of
interferon levels, we can now use this information to develop reagents that can
be applied in clinical and laboratory settings to further our understanding of
marsupial responses to disease.
PMID- 25124144
TI - ISA virus regulates the generation of reactive oxygen species and p47phox
expression in a p38 MAPK-dependent manner in Salmo salar.
AB - Several viruses, including Orthomyxovirus, utilize cellular reactive oxygen
species (ROS) for viral genomic replication and survival within host cells.
However, the role of ROS in early events of viral entry and signal induction has
not been elucidated. Here, we show that ISA virus (ISAV) induces ROS production
very early during infection of CHSE-214 and SHK-1Ycells, and that production is
sustained over the observed 24h post-infection. The mitogen-activated protein
kinase (MAPK) family is responsible for important signaling pathways. In this
study, we report that ISAV activates ERK and p38 in Salmo salar. In salmonid
macrophages, while ERK was required for SOD, GLURED, p47phox expression, p38
regulated the ROS production by the NADPH oxidase complex activation. These
results, together with the presence of several consensus target motifs for p38
MAPK in the promoter of the S. salar p47phox gene, suggest that p38 MAPK
regulates p47phox gene expression in fish through the activation of this key
transcription factor.
PMID- 25124145
TI - Complement activation-related pseudoallergy: a stress reaction in blood triggered
by nanomedicines and biologicals.
AB - Intravenous injection of a variety of nanotechnology enhanced (liposomal,
micellar, polymer-conjugated) and protein-based (antibodies, enzymes) drugs can
lead to hypersensitivity reactions (HSRs), also known as infusion, or
anaphylactoid reactions. The molecular mechanism of mild to severe allergy
symptoms may differ from case to case and is mostly not known, however, in many
cases a major cause, or contributing factor is activation of the complement (C)
system. The clinical relevance of C activation-related HSRs, a non-IgE-mediated
pseudoallergy (CARPA), lies in its unpredictability and occasional lethal
outcome. Accordingly, there is an unmet medical need to develop laboratory assays
and animal models that quantitate CARPA. This review provides basic information
on CARPA; a short history, issues of nomenclature, incidence, classification of
reactogenic drugs and symptoms, and the mechanisms of C activation via different
pathways. It is pointed out that anaphylatoxin-induced mast cell release may not
entirely explain the severe reactions; a "second hit" on allergy mediating cells
may also contribute. In addressing the increasing requirements for CARPA testing,
the review evaluates the available assays and animal models, and proposes a
possible algorithm for the screening of reactogenic drugs and hypersensitive
patients. Finally, an analogy is proposed between CARPA and the classic stress
reaction, suggesting that CARPA represents a "blood stress" reaction, a systemic
fight of the body against harmful biological and chemical agents via the
anaphylatoxin/mast-cell/circulatory system axis, in analogy to the body's fight
of physical and emotional stress via the hypothalamo/pituitary/adrenal axis. In
both cases the response to a broad variety of noxious effects are funneled into a
uniform pattern of physiological changes.
PMID- 25124146
TI - Global biogeography of Alnus-associated Frankia actinobacteria.
AB - Macroecological patterns of microbes have received relatively little attention
until recently. This study aimed to disentangle the determinants of the global
biogeographic community of Alnus-associated actinobacteria belonging to the
Frankia alni complex. By determining a global sequence similarity threshold for
the nitrogenase reductase (nifH) gene, we separated Frankia into operational
taxonomic units (OTUs) and tested the relative effects of Alnus phylogeny,
geographic relatedness, and climatic and edaphic variables on community
composition at the global scale. Based on the optimal nifH gene sequence
similarity threshold of 99.3%, we distinguished 43 Frankia OTUs from root systems
of 22 Alnus species on four continents. Host phylogeny was the main determinant
of Frankia OTU-based community composition, but there was no effect on the
phylogenetic structure of Frankia. Biogeographic analyses revealed the strongest
cross-continental links over the Beringian land bridge. Despite the facultative
symbiotic nature of Frankia, phylogenetic relations among Alnus species play a
prominent role in structuring root-associated Frankia communities and their
biogeographic patterns. Our results suggest that Alnus species exert strong
phylogenetically determined selection pressure on compatible Actinobacteria.
PMID- 25124147
TI - Congenital abnormalities of the vertebral column in ferrets.
AB - Vertebral column pathologies requiring surgical intervention have been described
in pet ferrets, however little information is available on the normal vertebral
formula and congenital variants in this species. The purpose of this
retrospective study was to describe vertebral formulas and prevalence of
congenital vertebral anomalies in a sample of pet ferrets. Radiographs of 172 pet
ferrets (96 males and 76 females) were included in this retrospective study. In
143 ferrets (83.14%), five different formulas of the vertebral column were
recorded with normal morphology of vertebrae (rib attachment included) but with a
variable number of thoracic (Th), lumbar (L), and sacral (S) vertebrae. The
number of cervical (C) vertebrae was constant in all examined animals. Observed
vertebral formulas were C7/Th14/L6/S3 (51.74%), C7/Th14/L6/S4 (22.10%),
C7/Th14/L7/S3 (6.98%), C7/Th15/L6/S3 (1.74%), and C7/Th15/L6/S4 (0.58%). Formula
C7/Th14/L6/S4 was significantly more common in males than in females (P < 0.05).
Congenital spinal abnormalities were found in 29 ferrets (16.86%), mostly
localized in the thoracolumbar and lumbosacral regions. The cervical region was
affected in only one case. Transitional vertebrae represented the most common
congenital abnormalities (26 ferrets) in the thoracolumbar (13 ferrets) and
lumbosacral regions (10 ferrets) or simultaneously in both regions (three
ferrets). Other vertebral anomalies included block (two ferrets) and wedge
vertebra (one ferret). Spina bifida was not detected. Findings from the current
study indicated that vertebral formulas may vary in ferrets and congenital
abnormalities are common. This should be taken into consideration for surgical
planning.
PMID- 25124149
TI - Expression of microRNA miR-126 and miR-200c is associated with prognosis in
patients with non-small cell lung cancer.
AB - MicroRNAs (miRNAs) are short non-coding RNAs that exert a critical influence on
tumorigenesis through post-transcriptional modification and are considered to be
potential biomarkers for the diagnosis or prognosis of various cancers. Although
several miRNAs have been proposed as relevant biomarkers for non-small cell lung
cancer (NSCLC), detailed working mechanisms and validated prognostic significance
of these miRNAs remain controversial. In this study, we evaluated expression
levels of miRNA-126 (miR-126) and miR-200c in 72 NSCLCs and 30 benign lung
tissues by quantitative reverse transcription polymerase chain reaction (qRT-PCR)
and analyzed the correlation of miRNA expression with a variety of
clinicopathological factors and patient survival. Compared with the benign
control group, miR-126 expression was significantly downregulated in NSCLCs (p <
0.001), while miR-200c expression was significantly upregulated in NSCLCs (p <
0.001). The expression of miR-126 was significantly higher in NSCLCs with a tumor
size of <=3 cm than in those with a tumor size of >3 cm (p = 0.026). There were
no other significant associations between miRNA expression and
clinicopathological features. In univariate survival analysis for all NSCLC
patients, high miR-200c expression (p = 0.037), large tumor size (p = 0.026), and
lymphovascular invasion (p = 0.012) were significantly correlated with worse
overall survival. High miR-126 expression was significantly associated with
favorable prognosis only in patients with adenocarcinoma (p = 0.033). In
multivariate analysis, miR-200c and tumor size remained as independent prognostic
factors. Our results suggest that miR-126 might play tumor-suppressive and miR
200c an oncogenic role, and these miR's are potential prognostic biomarkers for
NSCLC.
PMID- 25124148
TI - Pallidal gap junctions-triggers of synchrony in Parkinson's disease?
AB - Although increased synchrony of the neural activity in the basal ganglia may
underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this
synchrony arises, propagates through the basal ganglia, and changes under
dopamine replacement remains unknown. Gap junctions could play a major role in
modifying this synchrony, because they show functional plasticity under the
influence of dopamine and after neural injury. In this study, confocal imaging
was used to detect connexin-36, the major neural gap junction protein, in
postmortem tissues of PD patients and control subjects in the putamen,
subthalamic nucleus (STN), and external and internal globus pallidus (GPe and
GPi, respectively). Moreover, we quantified how gap junctions affect synchrony in
an existing computational model of the basal ganglia. We detected connexin-36 in
the human putamen, GPe, and GPi, but not in the STN. Furthermore, we found that
the number of connexin-36 spots in PD tissues increased by 50% in the putamen,
43% in the GPe, and 109% in the GPi compared with controls. In the computational
model, gap junctions in the GPe and GPi strongly influenced synchrony. The basal
ganglia became especially susceptible to synchronize with input from the cortex
when gap junctions were numerous and high in conductance. In conclusion, connexin
36 expression in the human GPe and GPi suggests that gap junctional coupling
exists within these nuclei. In PD, neural injury and dopamine depletion could
increase this coupling. Therefore, we propose that gap junctions act as a
powerful modulator of synchrony in the basal ganglia.
PMID- 25124150
TI - High users of emergency departments in Quebec among patients with both
schizophrenia and a substance use disorder.
AB - OBJECTIVE: The study assessed factors associated over time with high use of
emergency departments by patients in Quebec who had schizophrenia and a co
occurring substance use disorder. METHODS: The cohort study included 2,921
patients who received a diagnosis of schizophrenia in 2006 and had at least one
emergency department visit during fiscal year 2006-2007. Generalized estimating
equations were used to estimate predictors of high use of emergency departments
over time. RESULTS: After adjustment for all covariates, predictors of high use
over time were as follows: living in either a university medical region (OR=2.10)
or a peripheral medical region (OR=2.10), frequent hospitalization (OR=1.16), and
greater number of psychiatric (OR=1.64) or physical comorbidities (OR=1.23).
CONCLUSIONS: Because high use of emergency departments is a strong indicator of
poor care continuity, identified associated factors could help develop and offer
new programs to be deployed in the community to better support these patients
with greater needs.
PMID- 25124151
TI - Cochlear length determination using Cone Beam Computed Tomography in a clinical
setting.
AB - Indications for cochlear implants are determined by audiological and medical
considerations. Clinical imaging is therefore an integral element for anatomical
evaluation in terms of medical considerations. Several authors have discussed the
variability of cochlear shape, especially cochlear length. Cochlear length is,
however, an increasingly recognized parameter in terms of preoperative
evaluation. This study introduces a methodology to determine individual cochlear
length in clinical setting by using Cone Beam Computed Tomography. Cochlear
length determination was performed retrospectively with an OsiriX curved 3D
Multiplanar Reconstruction tool on subjects who underwent temporal bone imaging
from January 2011 to February 2013. Cochlear length was defined as the spiral
route from the center-distal point of the bony round window along the lateral
wall towards the helicotrema, which is the endpoint of the measurement. Cochlear
length was measured in 436 temporal bones (218 left ears, 218 right ears, 218
subjects). The mean cochlear length was 37.6 mm (SD: +/- 1.93 mm), median was
37.6 mm, range 32-43.5 mm. The cochlear length had a normal distribution. A
significant difference was found between cochlear length by gender (p < .0001),
but not between the left and right cochlea (p = .301) or according to age.
Consideration of the cochlear length in clinical data may be an insufficiently
represented parameter in cochlear implant treatment. Literature shows the impact
of electrode insertion depth on residual hearing preservation and speech
performance. Individual evaluation of the cochlear implant electrode choice may
be the next step in personalized cochlear implant treatment as a valuable
addition to existing audiological and surgical evaluation. The cochlear length
determination methodology presented herein is a reproducible and clinically
available parameter. Indeed, revealing a significant cochlear length span width,
especially according to gender differences, may be assumed as hardly ignorable.
PMID- 25124152
TI - Abnormal intelligibility of speech in competing speech and in noise in a
frequency region where audiometric thresholds are near-normal for hearing
impaired listeners.
AB - The ability to identify syllables in the presence of speech-shaped noise and a
single-talker background was measured for 18 normal-hearing (NH) listeners, and
for eight hearing-impaired (HI) listeners with near-normal audiometric thresholds
for frequencies up to 1.5 kHz and a moderate to severe hearing loss above 2 kHz.
The stimulus components were restricted to the low-frequency (<=1.5 kHz) region,
where audiometric thresholds were classified clinically as normal or near normal
for all listeners. Syllable identification in a speech background was measured as
a function of the fundamental-frequency (F0) difference between competing voices
(ranging from 1 semitone to ~1 octave). HI listeners had poorer syllable
intelligibility than NH listeners in all conditions. Intelligibility decreased by
about the same amount for both groups when the F0 difference between competing
voices was reduced. The results suggest that the ability to identify speech
against noise or an interfering talker was disrupted in frequency regions of near
normal hearing for HI listeners, but that the ability to benefit from the tested
F0 differences was not disrupted. This deficit was not predicted by the elevated
absolute thresholds for speech in speech, but it was for speech in noise. It may
result from supra-threshold auditory deficits associated with aging.
PMID- 25124153
TI - Differential modulation of auditory responses to attended and unattended speech
in different listening conditions.
AB - This study investigates how top-down attention modulates neural tracking of the
speech envelope in different listening conditions. In the quiet conditions, a
single speech stream was presented and the subjects paid attention to the speech
stream (active listening) or watched a silent movie instead (passive listening).
In the competing speaker (CS) conditions, two speakers of opposite genders were
presented diotically. Ongoing electroencephalographic (EEG) responses were
measured in each condition and cross-correlated with the speech envelope of each
speaker at different time lags. In quiet, active and passive listening resulted
in similar neural responses to the speech envelope. In the CS conditions,
however, the shape of the cross-correlation function was remarkably different
between the attended and unattended speech. The cross-correlation with the
attended speech showed stronger N1 and P2 responses but a weaker P1 response
compared to the cross-correlation with the unattended speech. Furthermore, the N1
response to the attended speech in the CS condition was enhanced and delayed
compared with the active listening condition in quiet, while the P2 response to
the unattended speaker in the CS condition was attenuated compared with the
passive listening in quiet. Taken together, these results demonstrate that top
down attention differentially modulates envelope-tracking neural activity at
different time lags and suggest that top-down attention can both enhance the
neural responses to the attended sound stream and suppress the responses to the
unattended sound stream.
PMID- 25124154
TI - Inner ear stem cells derived feeder layer promote directional differentiation of
amniotic fluid stem cells into functional neurons.
AB - Intact spiral ganglion neurons are required for cochlear implantation or
conventional hearing amplification as an intervention for sensorineural hearing
loss. Treatment strategies to replace the loss of spiral ganglion neurons are
needed. Recent reports have suggested that amniotic fluid-derived stem cells are
capable of differentiating into neuron-like cells in response to cytokines and
are not tumorigenic. Amniotic fluid stem cells represent a potential resource for
cellular therapy of neural deafness due to spiral ganglion pathology. However,
the directional differentiation of amniotic fluid stem cells is undetermined in
the absence of cytokines and the consequence of inner ear supporting cells from
the mouse cochlea organ of Corti on the differentiation of amniotic fluid stem
cells remains to be defined. In an effort to circumvent these limitations, we
investigated the effect of inner ear stem cells derived feeder layer on amniotic
fluid stem cells differentiation in vitro. An inner ear stem cells derived feeder
layer direct contact system was established to induce differentiation of amniotic
fluid stem cells. Our results showed that inner ear stem cells derived feeder
layer successfully promoted directional differentiation of amniotic fluid stem
cells into neurons with characteristics of functionality. Furthermore, we showed
that Wnt signaling may play an essential role in triggering neurogenesis. These
findings indicate the potential use of inner ear stem cells derived feeder layer
as a nerve-regenerative scaffold. A reliable and effective amniotic fluid stem
cell differentiation support structure provided by inner ear stem cells derived
feeder layer should contribute to efforts to translate cell-based strategies to
the clinic.
PMID- 25124155
TI - NIR spectroscopic method for the in-line moisture assessment during drying in a
six-segmented fluid bed dryer of a continuous tablet production line: Validation
of quantifying abilities and uncertainty assessment.
AB - This study focuses on the thorough validation of an in-line NIR based moisture
quantification method in the six-segmented fluid bed dryer of a continuous from
powder-to-tablet manufacturing line (ConsiGmaTM 25, GEA Pharma Systems nv,
Wommelgem, Belgium). The moisture assessment ability of an FT-NIR spectrometer
(MatrixTM-F Duplex, Bruker Optics Ltd, UK) equipped with a fiber-optic Lighthouse
ProbeTM (LHP, GEA Pharma Systems nv, Wommelgem, Belgium) was investigated.
Although NIR spectroscopy is a widely used technique for in-process moisture
determination, a minority of NIR spectroscopy methods is thoroughly validated. A
moisture quantification PLS model was developed. Twenty calibration experiments
were conducted, during which spectra were collected at-line and then regressed
versus the corresponding residual moisture values obtained via Karl Fischer
measurements. The developed NIR moisture quantification model was then validated
by calculating the accuracy profiles on the basis of the analysis results of
independent in-line validation experiments. Furthermore, as the aim of the NIR
method is to replace the destructive, time-consuming Karl Fischer titration, it
was statistically demonstrated that the new NIR method performs at least as good
as the Karl Fischer reference method.
PMID- 25124156
TI - Flow cytometric enumeration of bacteria using TO-PRO(r)-3 iodide as a single
stain viability dye.
AB - Quantification of bacteria using conventional viable plate counting (VPC) is
labor-intensive and time-consuming. Flow cytometry (FCM) can be proposed as a
faster alternative. This study aimed to develop a flow cytometric, single-stain
approach using TO-PRO(r)-3 iodide (TP3) for the quantification of Staphylococcus
aureus, Escherichia coli, and Bacillus subtilis cells. Live or dead bacterial
suspensions were stained with TP3 and analyzed using a FACSCalibur flow
cytometer. After optimization of staining parameters and instrument settings, an
excellent separation of viable and dead cells was achieved for all species. The
quantitative performance of the technique was assessed by analyzing serial
dilutions of bacterial suspensions using FCM and VPC. A highly linear correlation
(r2 > 0.99) was observed between the colony forming units (CFU)/mL as determined
by FCM and by VPC over a concentration range of about 104 to 108 CFU/mL. As such,
FCM quantification of viable bacteria using TP3 can be considered as an accurate
and reliable alternative for VPC. The monostain procedure is easy to apply and
cost-effective, and it allows bacterial enumeration in a broad variety of
samples.
PMID- 25124157
TI - Laboratory automation in a functional programming language.
AB - After some years of use in academic and research settings, functional languages
are starting to enter the mainstream as an alternative to more conventional
programming languages. This article explores one way to use Haskell, a functional
programming language, in the development of control programs for laboratory
automation systems. We give code for an example system, discuss some programming
concepts that we need for this example, and demonstrate how the use of functional
programming allows us to express and verify properties of the resulting code.
PMID- 25124158
TI - Reactions of rac-(ebthi)M(eta(2) -Me3 SiC2 SiMe3 ) (M=Ti, Zr) with aryl nitriles.
AB - The reactions of the Group 4 metallocene alkyne complexes rac-(ebthi)M(eta(2)
Me3 SiC2 SiMe3 ) (1 a: M=Ti, 1 b: M=Zr; rac-(ebthi)=rac-1,2-ethylene-1,1'
bis(eta(5) -tetrahydroindenyl)) with Ph?C?N were investigated. For 1 a, an
unusual nitrile-nitrile coupling to 1-titana-2,5-diazacyclopenta-2,4-diene (2) at
ambient temperature was observed. At higher temperature, the C?C coupling of two
nitriles resulted in the formation of a dinuclear complex with a four-membered
diimine bridge (3). The reaction of 1 b with Ph?C?N afforded dinuclear compound 4
and 2,4,6-triphenyltriazine. Additionally, the reactivity of 1 b towards other
nitriles was investigated.
PMID- 25124159
TI - A novel COL4A1 gene mutation results in autosomal dominant non-syndromic
congenital cataract in a Chinese family.
AB - BACKGROUND: Almost one-third of congenital cataracts are primarily autosomal
dominant disorders, which are also called autosomal dominant congenital cataract,
resulting in blindness and clouding of the lens. The purpose of this study was to
identify the disease-causing mutation in a Chinese family affected by bilateral,
autosomal dominant congenital cataract. METHODS: The detection of candidate gene
mutation and the linkage analysis of microsatellite markers were performed for
the known candidate genes. Molecular mapping and cloning of candidate genes were
used in all affected family members to screen for potential genetic mutations and
the mutation was confirmed by single enzyme digestion. RESULTS: The proband was
diagnosed with isolated, congenital cataract without the typical clinical
manifestations of cataract, which include diabetes, porencephaly, sporadic
intracerebral hemorrhage, and glomerulopathy. A novel mutation, c.2345 G > C
(Gly782Ala), in exon 31 of the collagen type IV alphalpha1 (COL4A1) gene, which
encodes the collagen alpha-1(IV) chain, was found to be associated with autosomal
dominant congenital cataract in a Chinese family. This mutation was not found in
unaffected family members or in 200 unrelated controls. Sequence analysis
confirmed that the Gly782 amino acid residue is highly conserved. CONCLUSIONS:
The novel mutation (c.2345 G > C) of the COL4A1 gene is the first report of a non
syndromic, autosomal dominant congenital cataract, thereby highlighting the
important role of type IV collagen in the physiological and optical properties of
the lens.
PMID- 25124160
TI - Real-time near-infrared fluorescence guided surgery in gynecologic oncology: a
review of the current state of the art.
AB - Near-infrared (NIR) fluorescence imaging has emerged as a promising complimentary
technique for intraoperative visualization of tumor tissue, lymph nodes and vital
structures. In this review, the current applications and future opportunities of
NIR fluorescence imaging in gynecologic oncology are summarized. Several studies
indicate that intraoperative sentinel lymph node identification in vulvar cancer
using NIR fluorescence imaging outperforms blue dye staining and provides real
time intraoperative imaging of sentinel lymph nodes. NIR fluorescence imaging can
penetrate through several millimeters of tissue, revealing structures just below
the tissue surface. Hereby, iatrogenic damage to vital structures, such as the
ureter or nerves may be avoided by identification using NIR fluorescence imaging.
Tumor-targeted probes are currently being developed and have the potential to
improve surgical outcomes of cytoreductive and staging procedures, in particular
in ovarian cancer. Research in the near future will be necessary to determine
whether this technology has additional value in order to facilitate the surgical
procedure, reduce morbidity and improve disease-free and overall survival.
PMID- 25124162
TI - SGO guidance document for clinical trial designs in ovarian cancer: a changing
paradigm.
AB - OBJECTIVE: To explore and facilitate the multifaceted process of drug development
and regulatory approval in ovarian cancer. METHODS: The Society of Gynecologic
Oncology (SGO) recently sought and received input from multiple stakeholders
including the National Cancer Institute's (NCI) Clinical Therapy Evaluation
Program (CTEP), the Food and Drug Administration (FDA), pharmaceutical industry,
and patient advocates. This whitepaper is the work product and opinion solely of
the SGO. RESULTS: This document summarizes the SGO's interpretation of these
meetings and the current regulatory environment where there has been a paucity of
recent approvals in the United States. It provides guidance in clinical trial
design with the express purpose of encouraging novel drug development in ovarian
cancer. Points of emphasis include: ovarian cancer heterogeneity (histologic
subtypes and molecular genetic alterations), clinical trial design elements,
surrogate as well as composite endpoints, and the four principles of clinical
drug development (unmet medical need, discovery, safety, and efficacy).
CONCLUSIONS: There has been an evolution in the acceptance of surrogate endpoints
depending upon the clinical setting in ovarian cancer. While overall survival
(OS) remains the most objective clinical trial endpoint, there is now realization
that demanding OS as the primary endpoint has many obstacles. Ovarian cancer is a
heterogeneous disease that is now divided by histologic subtypes. Future
registration strategies will need to address disease heterogeneity. The
exploration of currently acceptable clinical trial endpoints and alternative
regulatory strategies will hopefully stimulate interest in novel drug development
for patients with ovarian cancer.
PMID- 25124161
TI - Neratinib shows efficacy in the treatment of HER2/neu amplified uterine serous
carcinoma in vitro and in vivo.
AB - OBJECTIVES: Uterine serous carcinoma (USC) represents an aggressive variant of
endometrial cancer and accounts for a large proportion of deaths annually.
HER2/neu amplification is associated with USC in approximately 30-35% of cases.
The objective of this study was to determine the sensitivity of a panel of
primary USC cell lines to the small tyrosine kinase inhibitor neratinib, an ErbB1
and HER2 inhibitor, both in vitro and in vivo. METHODS: HER2/neu amplification
was determined by immunohistochemistry (IHC) and fluorescence in situ
hybridization (FISH) in 24 USC cell lines. Flow cytometry was used to determine
the effects of neratinib on cell viability, cell cycle distribution and signaling
in vitro. Mice harboring HER2/neu amplified xenografts were treated with
neratinib to assess the efficacy of the drug in vivo. RESULTS: HER2/neu
amplification was noted in 8/24 primary cell lines. Data regarding the efficacy
of neratinib was determined using 4 HER2 amplified cell lines and 4 non-amplified
cell lines with similar growth rates. Data revealed that cell lines with HER2/neu
amplification were exquisitely more sensitive to neratinib compared to non
amplified cell lines (mean +/- SEM IC50: 0.011MUM +/- 0.0008 vs. 0.312MUM +/-
0.0456 p<0.0001). Neratinib caused arrest in the G0/G1 phase of the cell cycle
and resulted in decreased autophosphorylation of HER2 and activation of S6.
Neratinib treated mice harboring xenografts of HER2/neu amplified USC showed
delayed tumor growth and improved overall survival compared to vehicle
(p=0.0019). CONCLUSIONS: Neratinib may be a potential treatment option for
patients harboring HER2/neu amplified USC. Clinical trials for this subset of
endometrial cancer patients are warranted.
PMID- 25124164
TI - Vitamin E and wound healing: an evidence-based review.
AB - Vitamin E has been demonstrated to modulate cellular signalling, gene expression
and affect wounds infected with methicillin-resistant Staphylococcus aureus
(MRSA), thus influencing wound healing. This evidence-based review aimed to
identify and evaluate current research assessing the properties of vitamin E in
relation to wound healing, through its role as an antioxidant and its influence
on connective tissue growth factor (CTGF), MRSA and gene transcription.
Literature dated from 1996 to 2012, published in English, involving either
animals or adult humans with an acute or chronic wound were included. The
databases that contained relevant articles were narrowed down to four, and a
total of 33 identified studies were included. The literature review revealed that
there is a significant dearth of robust studies establishing the effects of
vitamin E on wound healing, and further research is clearly warranted.
PMID- 25124163
TI - Mutations in POLE and survival of colorectal cancer patients--link to disease
stage and treatment.
AB - Recent molecular profiling studies reported a new class of ultramutated
colorectal cancers (CRCs), which are caused by exonuclease domain mutations
(EDMs) in DNA polymerase epsilon (POLE). Data on the clinical implications of
these findings as to whether these mutations define a unique CRC entity with
distinct clinical outcome are lacking. We performed Sanger sequencing of the POLE
exonuclease domain in 431 well-characterized patients with microsatellite stable
(MSS) CRCs of a population-based patient cohort. Mutation data were analyzed for
associations with major epidemiological, clinical, genetic, and pathological
parameters including overall survival (OS) and disease-specific survival (DSS).
In 373 of 431 MSS CRC, all exons of the exonuclease domain were analyzable. Fifty
four mutations were identified in 46 of these samples (12.3%). Besides already
reported EDMs, we detected many new mutations in exons 13 and 14 (corresponding
to amino acids 410-491) as well as in exon 9 and exon 11 (corresponding to aa 268
303 and aa 341-369). However, we did not see any significant associations of EDMs
with clinicopathological parameters, including sex, age, tumor location and tumor
stage, CIMP, KRAS, and BRAF mutations. While with a median follow-up time of 5.0
years, survival analysis of the whole cohort revealed nonsignificantly different
adjusted hazard ratios (HRs) of 1.35 (95% CI: 0.82-2.25) and 1.44 (0.81-2.58) for
OS and DSS indicating slightly impaired survival of patients with EDMs, subgroup
analysis for patients with stage III/IV disease receiving chemotherapy revealed a
statistically significantly increased adjusted HR (1.87; 95%CI: 1.02-3.44). In
conclusion, POLE EDMs do not appear to define an entirely new clinically distinct
disease entity in CRC but may have prognostic or predictive implications in CRC
subgroups, whose significance remains to be investigated in future studies.
PMID- 25124165
TI - Quantifying the influence of the tobacco industry on EU governance: automated
content analysis of the EU Tobacco Products Directive.
AB - OBJECTIVE: The tobacco industry spends large sums lobbying the European Union
(EU) institutions, yet whether such lobbying significantly affects tobacco policy
is not well understood. We used novel quantitative text mining techniques to
evaluate the impact of industry pressure on the contested EU Tobacco Products
Directive revision. DESIGN: Policy positions of 18 stakeholders including the
tobacco industry, health NGOs and tobacco retailers were evaluated using their
text submissions to EU consultations and impact assessments. Using Wordscores to
calculate word frequencies, we developed a scale ranging from 0-tobacco industry
to 1-public health organisations, which was then used to track changes in the
policy position of the European Commission's 2010 consultation document, its 2012
final proposal and the European Parliament and Council's approved legislation in
March 2014. RESULTS: Several stakeholders' positions were closer to the tobacco
industry than that of health NGOs, including retailers (omega=0.35), trade unions
(omega=0.34) and publishers (omega=0.33 and omega=0.40). Over time the European
Commission's position shifted towards the tobacco industry from omega=0.52 (95%
CI 0.50 to 0.54) to omega=0.40 (95% CI 0.39 to 0.42). This transition reflected
an increasing use of words pertaining to business and the economy in the
Commission's document. Our findings were robust to alternative methods of scoring
policy positions in EU documents. CONCLUSIONS: Using quantitative text mining
techniques, we observed that tobacco industry lobbying activity at the EU was
associated with significant policy shifts in the EU Tobacco Products Directive
legislation towards the tobacco industry's submissions. In the light of the
Framework Convention on Tobacco Control, additional governance strategies are
needed to prevent undue influence of the tobacco industry on EU policy making.
PMID- 25124166
TI - Mental health/illness and prisons as place: frontline clinicians' perspectives of
mental health work in a penal setting.
AB - This article takes mental health and prisons as its two foci. It explores the
links between social and structural aspects of the penal setting, the provision
of mental healthcare in prisons, and mental health work in this environment. This
analysis utilises qualitative interview data from prison-based fieldwork
undertaken in Her Majesty's Prison Service, England. Two themes are discussed:
(1) the desire and practicalities of doing mental health work and (2) prison
staff as mental health work allies. Concepts covered include equivalence,
training, ownership, informal communication, mental health knowledge, service
gatekeepers, case identification, and unmet need. Implications for practice are
(1) the mental health knowledge and understanding of prison wing staff could be
appraised and developed to improve mental healthcare and address unmet need.
Their role as observers and gatekeepers could be considered. (2) The realities of
frontline mental health work for clinicians in the penal environment should be
embraced and used to produce and implement improved policy and practice guidance,
which is in better accord with the actuality of the context - both socially and
structurally.
PMID- 25124167
TI - Sample size importantly limits the usefulness of instrumental variable methods,
depending on instrument strength and level of confounding.
AB - OBJECTIVES: Instrumental variable (IV) analysis is promising for estimation of
therapeutic effects from observational data as it can circumvent unmeasured
confounding. However, even if IV assumptions hold, IV analyses will not
necessarily provide an estimate closer to the true effect than conventional
analyses as this depends on the estimates' bias and variance. We investigated how
estimates from standard regression (ordinary least squares [OLS]) and IV (two
stage least squares) regression compare on mean squared error (MSE). STUDY
DESIGN: We derived an equation for approximation of the threshold sample size,
above which IV estimates have a smaller MSE than OLS estimates. Next, we
performed simulations, varying sample size, instrument strength, and level of
unmeasured confounding. IV assumptions were fulfilled by design. RESULTS:
Although biased, OLS estimates were closer on average to the true effect than IV
estimates at small sample sizes because of their smaller variance. The threshold
sample size above which IV analysis outperforms OLS regression depends on
instrument strength and strength of unmeasured confounding but will usually be
large given the typical moderate instrument strength in medical research.
CONCLUSION: IV methods are of most value in large studies if considerable
unmeasured confounding is likely and a strong and plausible instrument is
available.
PMID- 25124170
TI - Graphical fault tree analysis for fatal falls in the construction industry.
AB - The current study applied a fault tree analysis to represent the causal
relationships among events and causes that contributed to fatal falls in the
construction industry. Four hundred and eleven work-related fatalities in the
Taiwanese construction industry were analyzed in terms of age, gender,
experience, falling site, falling height, company size, and the causes for each
fatality. Given that most fatal accidents involve multiple events, the current
study coded up to a maximum of three causes for each fall fatality. After the
Boolean algebra and minimal cut set analyses, accident causes associated with
each falling site can be presented as a fault tree to provide an overview of the
basic causes, which could trigger fall fatalities in the construction industry.
Graphical icons were designed for each falling site along with the associated
accident causes to illustrate the fault tree in a graphical manner. A graphical
fault tree can improve inter-disciplinary discussion of risk management and the
communication of accident causation to first line supervisors.
PMID- 25124171
TI - Editorial. Veterinary dermatology over 25 years.
PMID- 25124168
TI - Side effects are incompletely reported among systematic reviews in
gastroenterology.
AB - OBJECTIVES: Systematic reviews are an integral component of evidence-based health
care. However, little is known on how well they report the potential harms of
interventions. We assessed the reporting of harms in recently published
systematic reviews of interventions relevant to clinical gastroenterology. STUDY
DESIGN: We identified all systematic reviews of randomized trials of
gastroenterology interventions published from 2008 to 2012 in highly cited
gastroenterology and general medical journals. We adapted the Consolidated
Standards of Reporting Trials guidelines for harms and assessed qualitative and
quantitative parameters of harms reporting. Regression analyses determined
predictors of more comprehensive harms reporting. RESULTS: In total, 78
systematic reviews were identified, with 72 published in gastroenterology
journals and six in general medical journals. Overall, one in three systematic
reviews (26/78, 33%) did not refer to harms of the intervention anywhere in the
article. Less than half of the studies included adverse events as an outcome
measure, and data on absolute rates of adverse events were only provided in 28%.
Most (65%) did not include any figures or tables on adverse event; however, all
included these on efficacy outcomes (mean, 3 and range, 1-7). Regression analyses
indicated that the use of reporting guidelines was significantly associated with
better harms reporting (P = 0.04). CONCLUSION: The reporting of harms in
gastroenterology systematic reviews is largely inadequate and highly asymmetrical
compared with the reporting of benefits. We suggest that review authors routinely
assess both efficacy and harms outcomes of an intervention and that reporting
guidelines specifically targeting harms reporting be developed.
PMID- 25124172
TI - Keratinocyte biology and pathology.
PMID- 25124173
TI - Veterinary dermatology and dermatopathology.
PMID- 25124169
TI - Intratracheal co-administration of antioxidants and ceftriaxone reduces pulmonary
injury and mortality rate in an experimental model of sepsis.
AB - BACKGROUND AND OBJECTIVE: Recent studies showed that both sepsis and antibiotic
therapy are associated with cell death and linked to reactive oxygen species
generation. This study investigated the effects of intratracheal administration
of combinations of antioxidants (n-acetyl cysteine (NAC), vitamins C and E) in
the treatment of sepsis-induced lung injury. METHODS: Ninety-six male Wistar rats
subjected to sepsis were treated with ceftriaxone plus NAC with or without
vitamins C and E and compared to appropriate controls. As an index of oxidative
damage protein carbonyls, sulfhydryl groups, lipid peroxidation and superoxide
anion were measured, as well as superoxide dismutase and catalase.
Histopathological alterations and mortality rate were also analyzed. RESULTS:
Twenty-four hours after sepsis induction, markers of oxidative stress increased
in all lungs examined. Ceftriaxone plus intratracheal combination of NAC,
vitamins C and E decreased lung injury in infected animals by reducing superoxide
anion production (54%), lipid peroxidation (53%) and protein carbonyl (58%) and
restored the redox status (7.5 times). This therapy also reduced the imbalance of
antioxidant enzymes activities and attenuated the alveolar architectural
disorganization, inflammatory cell infiltration and pulmonary oedema. Survival
increased from 66.6% with ceftriaxone to 83.2% with ceftriaxone plus
antioxidants. CONCLUSIONS: Ceftriaxone plus intratracheal co-administration of
antioxidants provides better protection, by decreasing pulmonary oxidative
stress, limiting histophatological alterations and improving survival.
Antioxidants should be explored as a co-adjuvant in the treatment of severe lung
injury.
PMID- 25124175
TI - The 'spore of Malassez' as a canine skin pathogen: lessons from history?
PMID- 25124174
TI - Pyoderma, the march of the staphylococci.
PMID- 25124176
TI - Insights into immunoglobulin E-mediated late-phase reactions in dogs.
PMID- 25124177
TI - An autoimmune subepidermal blistering skin disease in a dog? The odds are that it
is not bullous pemphigoid.
PMID- 25124178
TI - The secret sits.
PMID- 25124179
TI - Orf.
PMID- 25124180
TI - Equine dermatology - past, present and future.
PMID- 25124181
TI - Systemic signalling in photosynthetic induction of Rumex K-1 (Rumex patientia *
Rumex tianschaious) leaves.
AB - The rapid induction of photosynthesis is critical for plants under light-fleck
environment. Most previous studies about photosynthetic induction focused upon
single leaf, but they did not consider the systemic integrity of plant. Here, we
verified whether systemic signalling is involved in photosynthetic induction.
Rumex K-1 (Rumex patientia * Rumex tianschaious) plants were grown under light
fleck condition. After whole night dark adaptation, different numbers of leaves
(system leaf or SL) were pre-illuminated with light, and then the photosynthetic
induction of other leaves (target leaf or TL) was investigated. This study showed
that the pre-illumination of SL promoted photosynthetic induction in TL. This
promotion was independent of the number of SL, the light intensity on SL and the
distance between SL and TL, indicating that this systemic signalling is non-dose
dependent. More interestingly, the photosynthetic induction was promoted by only
the pre-illumination of morphological upper leaf rather than the pre-illumination
of morphological lower leaf, indicating that the transfer of this signal is
directional. The results showed that the transfer of this systemic signalling
depends upon the phloem. This systemic signalling helps plants to use light
energy more efficiently under light flecks.
PMID- 25124182
TI - Motor and cognitive deficits in aged tau knockout mice in two background strains.
AB - BACKGROUND: We recently reported that Parkinsonian and dementia phenotypes emerge
between 7-12 months of age in tau-/- mice on a Bl6/129sv mixed background. These
observations were partially replicated by another group using pure Bl6 background
tau-/- mice, but notably they did not observe a cognitive phenotype. A third
group using Bl6 background tau-/- mice found cognitive impairment at 20-months of
age. RESULTS: To reconcile the observations, here we considered the genetic,
dietary and environmental variables in both studies, and performed an extended
set of behavioral studies on 12-month old tau+/+, tau+/-, and tau-/- mice
comparing Bl6/129sv to Bl6 backgrounds. We found that tau-/- in both backgrounds
exhibited reduced tyrosine hydroxylase-positive nigral neuron and impaired motor
function in all assays used, which was ameliorated by oral treatment with L-DOPA,
and not confounded by changes in body weight. Tau-/- in the C57BL6/SV129
background exhibited deficits in the Y-maze cognition task, but the mice on the
Bl6 background did not. CONCLUSIONS: These results validate our previous report
on the neurodegenerative phenotypes of aged tau-/- mice, and show that genetic
background may impact the extent of cognitive impairment in these mice. Therefore
excessive lowering of tau should be avoided in therapeutic strategies for AD.
PMID- 25124184
TI - Comparison of five-year outcomes of coronary artery bypass grafting versus
percutaneous coronary intervention in patients with left ventricular ejection
fractions<=50% versus >50% (from the CREDO-Kyoto PCI/CABG Registry Cohort-2).
AB - Coronary heart disease is a major risk factor for left ventricular (LV) systolic
dysfunction. However, limited data are available regarding long-term benefits of
percutaneous coronary intervention (PCI) in the era of drug-eluting stent or
coronary artery bypass grafting (CABG) in patients with LV systolic dysfunction
with severe coronary artery disease. We identified 3,584 patients with 3-vessel
and/or left main disease of 15,939 patients undergoing first myocardial
revascularization enrolled in the CREDO-Kyoto PCI/CABG Registry Cohort-2. Of
them, 2,676 patients had preserved LV systolic function, defined as an LV
ejection fraction (LVEF) of >50% and 908 had impaired LV systolic function
(LVEF<=50%). In patients with preserved LV function, 5-year outcomes were not
different between PCI and CABG regarding propensity score-adjusted risk of all
cause and cardiac deaths. In contrast, in patients with impaired LV systolic
function, the risks of all-cause and cardiac deaths after PCI were significantly
greater than those after CABG (hazard ratio 1.49, 95% confidence interval 1.04 to
2.14, p=0.03 and hazard ratio 2.39, 95% confidence interval 1.43 to 3.98,
p<0.01). In both patients with moderate (35%= 3. After controlling for
age, preoperative hemoglobin, preoperative albumin, cancer stage, and adverse
pathologic features, transfusion of >= 3 (versus 0 to 2) units was associated
with poorer OS (P = 0.0006; hazard ratio [HR] = 2.96) and RFS (P = 0.003; HR =
2.35). The rates of wound infection in patients who received 0, 1, 2, or >= 3
units were 13.3%, 21.2%, 33.3%, and 31.2%, respectively. There was a
statistically significant difference in wound infection rates between those
patients receiving 0 to 1 versus >= 2 units (P = 0.04). CONCLUSIONS: Patients who
receive >= 3 units of blood after free tissue transfer for HNC had a
significantly increased risk of death after controlling for age, preoperative
hemoglobin and albumin, cancer stage, and adverse pathologic features. Increased
transfusions are also associated with higher wound infection rates. The increased
tendency to transfuse free flap patients in order to maintain a threshold
hematocrit may have a detrimental impact on survival and wound infections and
should be revisited.
PMID- 25124185
TI - An intervention to address secondhand tobacco smoke exposure among nonsmokers
hospitalized with coronary heart disease.
AB - Secondhand tobacco smoke (SHS) exposure increases nonsmokers' risk of coronary
heart disease and worsens outcomes after hospitalization for acute coronary
syndrome, but it is rarely addressed in inpatient cardiac care. We developed and
assessed a hospital-based intervention to increase nonsmokers' awareness of SHS
as a cardiovascular risk factor. Nonsmokers admitted to 2 cardiac units of a
large Boston, Massachusetts, hospital were surveyed before (May 2010 to January
2011) and after (November 2011 to March 2012) a system-level nurse-delivered
intervention was implemented in October 2011. It consisted of a revised admission
form that prompted nurses to document SHS exposure at admission, provide a
pamphlet about SHS risks, and advise nonsmokers to make their home and car smoke
free. The primary outcome was patients' short-term recall of advice to keep their
home and car smoke free. The secondary outcome was patients' awareness of the
cardiovascular risk of SHS exposure. We enrolled 190 nonsmokers before and 142
nonsmokers after implementation. Adjusting for group differences, patients
admitted after the system change were more likely to recall being asked if a
household member smokes (24% vs 10%, adjusted odds ratio [AOR] 3.6, 95%
confidence interval [CI] 1.8 to 7.1, p=0.0002) and being advised to keep their
home and car smoke free (28% vs 2%, AOR 27.3, 95% CI 7.8 to 95.7, p<0.0001).
After the intervention, more patients believed that SHS exposure increased
cardiovascular risk for nonsmokers (42% vs 21%, AOR 2.6, 95% CI 1.6 to 4.4) and
for themselves (39% vs 22%, AOR 2.2, 95% CI 1.3 to 3.8). In conclusion, a system
level intervention in cardiac units successfully increased hospitalized
nonsmokers' awareness of the cardiovascular risk of SHS exposure.
PMID- 25124187
TI - Frequency and clinical outcomes of ESKAPE bacteremia in solid organ
transplantation and the risk factors for mortality.
AB - BACKGROUND: Although bacteremias caused by the 6 ESKAPE pathogens (Enterococcus
faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii,
Pseudomonas aeruginosa, and Enterobacter species) have recently been highlighted
as a serious complication in solid organ transplant (SOT), more information is
urgently needed. We sought to investigate the frequency and clinical outcomes of
ESKAPE bacteremia in SOT and determine the risk factors for mortality. METHODS: A
retrospective analysis of bacteremia after SOT was reviewed. Risk factors for
mortality caused by ESKAPE bacteremia were identified. RESULTS: Eighty-four
episodes of bacteremia were caused by ESKAPE strains. Of these strains, 41 were
caused by resistant ESKAPE (rESKAPE) organisms. The only factor for bacteremia
related mortality independently associated with ESKAPE was septic shock (odds
ratio [OR] = 21.017, 95% confidence interval [CI] = 5.038-87.682, P < 0.001). The
factors for bacteremia-related mortality independently associated with rESKAPE
bacteremia were septic shock (OR = 16.558, 95% CI = 6.620-104.668, P = 0.003) and
age >=40 years (OR = 7.521, 95% CI = 1.196-47.292, P = 0.031). CONCLUSIONS: To
improve the outcomes of transplantation, more effective therapeutic treatments
are of paramount importance when older SOT recipients with bacteremia due to
ESKAPE/rESKAPE organisms present with septic shock.
PMID- 25124188
TI - What does your neighbourhood say about you? A study of life expectancy in 1.3
million Swiss neighbourhoods.
AB - BACKGROUND: Switzerland had the highest life expectancy at 82.8 years among the
Organisation for Economic Co-operation and Development (OECD) countries in 2011.
Geographical variation of life expectancy and its relation to the socioeconomic
position of neighbourhoods are, however, not well understood. METHODS: We
analysed the Swiss National Cohort, which linked the 2000 census with mortality
records 2000-2008 to estimate life expectancy across neighbourhoods. A
neighbourhood index of socioeconomic position (SEP) based on the median rent,
education and occupation of household heads and crowding was calculated for 1.3
million overlapping neighbourhoods of 50 households. We used skew-normal
regression models, including the index and additionally marital status,
education, nationality, religion and occupation to calculate crude and adjusted
estimates of life expectancy at age 30 years. RESULTS: Based on over 4.5 million
individuals and over 400,000 deaths, estimates of life expectancy at age 30 in
neighbourhoods ranged from 46.9 to 54.2 years in men and from 53.5 to 57.2 years
in women. The correlation between life expectancy and neighbourhood SEP was
strong (r=0.95 in men and r=0.94 women, both p values <0.0001). In a comparison
of the lowest with the highest percentile of neighbourhood SEP, the crude
difference in life expectancy from skew-normal regression was 4.5 years in men
and 2.5 years in women. The corresponding adjusted differences were 2.8 and 1.9
years, respectively (all p values <0.0001). CONCLUSIONS: Although life expectancy
is high in Switzerland, there is substantial geographical variation and life
expectancy is strongly associated with the social standing of neighbourhoods.
PMID- 25124186
TI - Comparison of stenting and surgical revascularization strategy in non-ST
elevation acute coronary syndromes and complex coronary artery disease (from the
Milestone Registry).
AB - The optimal revascularization strategy in patients with complex coronary artery
disease and non-ST-segment elevation acute coronary syndromes is undetermined. In
this multicenter, prospective registry, 4,566 patients with non-ST-segment
elevation myocardial infarctions, unstable angina, and multivessel coronary
disease, including left main disease, were enrolled. After angiography, 3,033
patients were selected for stenting (10.3% received drug-eluting stents) and
1,533 for coronary artery bypass grafting. Propensity scores were used for
baseline characteristic matching and result adjustment. Patients selected for
percutaneous coronary intervention (PCI) were younger (mean age 64.4+/-10 vs
65.2+/-9 years, p=0.03) and more frequently presented with non-ST-segment
elevation myocardial infarctions (32.0% vs 14.5%, p=0.01), cardiogenic shock
(1.5% vs 0.7%, p<0.01), and history of PCI (13.1% vs 5.5%, p<0.01) or coronary
artery bypass grafting (10.6% vs 4.6%, p<0.01). European System for Cardiac
Operative Risk Evaluation scores were higher in PCI patients (5.4+/-2 vs 5.2+/-2,
p<0.01). Patients referred for coronary artery bypass grafting more often
presented with triple-vessel disease and left main disease (82.2% vs 33.8% and
13.7% vs 2.4%, respectively, p<0.01). After adjustment, 929 well-matched pairs
were chosen. Early mortality was lower after PCI before matching (2.1% vs 3.1%,
p<0.01), whereas after balancing, there was no difference (2.5% vs 2.8%, p=0.62).
Three-year survival was in favor of PCI compared with surgery before (87.5% vs
82.8%, hazard ratio 1.44, 95% confidence interval 1.2 to 1.7, p<0.01) and after
(86.4% vs 82.3%, hazard ratio 1.33, 95% confidence interval 1.05 to 1.7, p=0.01).
Stenting was associated with improved outcomes in the following subgroups:
patients aged >65 years, women, patients with unstable angina, those with
European System for Cardiac Operative Risk Evaluation scores>5, those with
Thrombolysis In Myocardial Infarction (TIMI) risk scores >4, those receiving drug
eluting stents, and those with 2-vessel disease. In conclusion, in patients
presenting with non-ST-segment elevation acute coronary syndromes and complex
coronary artery disease, immediate stenting was associated with lower mortality
risk in the long term compared with surgical revascularization, especially in
subgroups at high clinical risk.
PMID- 25124189
TI - Risk relativism and physical law.
AB - In two 1959 papers, one coauthored, Jerome Cornfield asserts that 'relative'
measures are more useful for causal inference while 'absolute' measures are more
useful for public health purposes. In one of these papers (the single-authored
one), he asks how epidemiology should respond to the fact that its domain is not
a highly 'articulated' one-it is not susceptible to being subsumed under general
laws. What is the connection between these issues? There has recently been some
backlash against 'risk relativism', and Charles Poole has recently dismantled the
mathematical argument for the first claim. However the problem with 'Cornfield's
Principle' seems to go much deeper. The whole attempt to partition measures into
absolute and relative is fundamentally mistaken. Why, then, has it seemed so
appealing? Perhaps one reason is the influence that early education in the
physical sciences continues to exert on the way epidemiologists think, and their
response to the low articulation of their domain of study.
PMID- 25124190
TI - Educational differences in mortality and the relative importance of different
causes of death: a 7-year follow-up study of Spanish adults.
AB - BACKGROUND: The evidence on mortality patterns by education in Spain comes from
regional areas. This study aimed to estimate these patterns in the whole Spanish
population. METHODS: All citizens aged 25 years and over and residing in Spain in
2001 were followed during 7 years to determine their vital status, resulting in a
total of 196,470,401 person-years and 2,379,558 deaths. We estimated the age
adjusted total and cause-specific mortality by educational level-primary, lower
secondary, upper secondary and university education-and then calculated the
relative and absolute measures of inequality in mortality and contribution of the
leading causes of death to absolute inequalities. RESULTS: Except for some cancer
sites, the mortality rate for the leading causes of death shows an inverse
gradient with educational level. The leading causes of death with the highest
relative index of inequality ratios were HIV disease (9.81 in women and 11.61 in
men), diabetes in women (4.02) and suicide in men (3.52). The leading causes of
death that contribute most to the absolute inequality in mortality are
cardiovascular diseases (48.8%), respiratory diseases (9.3%) and diabetes
mellitus (8.8%) in women, and cardiovascular diseases (20.8%), respiratory
diseases (19.8%) and cancer (19.6%) in men. CONCLUSIONS: Although the causes of
death with the strongest gradient in mortality rate are HIV disease in both
sexes, diabetes mellitus in women and suicide in men, most of the absolute
education-related inequalities in total mortality are due to cardiovascular
diseases, respiratory diseases and diabetes mellitus in women and to
cardiovascular diseases, respiratory diseases and cancer in men.
PMID- 25124191
TI - Collective-efficacy as a mediator of the relationship of leaders' personality
traits and team performance: A cross-level analysis.
AB - The relationship between a leader's personality and his team's performance has
been established in organisational research, but the underlying process and
mechanism responsible for this effect have not been fully explored. Both the
traditional multiple linear regression and the multilevel structural equation
model approaches were used in this study to test a proposed mediating model of
subordinates' perception of collective efficacy between leader personality and
team performance. The results show that the team leader's extraversion and
conscientiousness personality traits were related positively to both the team
average (individual) perception of collective efficacy and team performance, and
the collective efficacy mediated the relationship of the leader's personality
traits and team performance. This study also discusses how Chinese cultural
elements play a role in such a mediating model.
PMID- 25124192
TI - Identification and characterisation of multiple glutathione S-transferase genes
from the diamondback moth, Plutella xylostella.
AB - BACKGROUND: The diamondback moth (DBM), Plutella xylostella, is one of the most
harmful insect pests on crucifer crops worldwide. In this study, 19 cDNAs
encoding glutathione S-transferases (GSTs) were identified from the genomic and
transcriptomic database for DBM (KONAGAbase) and further characterized. RESULTS:
Phylogenetic analysis showed that the 19 GSTs were classified into six different
cytosolic classes, including four in delta, six in epsilon, three in omega, two
in sigma, one in theta and one in zeta. Two GSTs were unclassified. RT-PCR
analysis revealed that most GST genes were expressed in all developmental stages,
with higher expression in the larval stages. Six DBM GSTs were expressed at the
highest levels in the midgut tissue. Twelve purified recombinant GSTs showed
varied enzymatic properties towards 1-chloro-2,4-dinitrobenzene and glutathione,
whereas rPxGSTo2, rPxGSTz1 and rPxGSTu2 had no activity. Real-time quantitative
PCR revealed that expression levels of the 19 DBM GST genes were varied and
changed after exposure to acephate, indoxacarb, beta-cypermethrin and spinosad.
PxGSTd3 was significantly overexpressed, while PxGSTe3 and PxGSTs2 were
significantly downregulated by all four insecticide exposures. CONCLUSION: The
changes in DBM GST gene expression levels exposed to different insecticides
indicate that they may play individual roles in tolerance to insecticides and
xenobiotics.
PMID- 25124194
TI - The use of chaperones during sensitive examinations and treatments.
PMID- 25124195
TI - Harvesting solar light with crystalline carbon nitrides for efficient
photocatalytic hydrogen evolution.
AB - Described herein is the photocatalytic hydrogen evolution using crystalline
carbon nitrides (CNs) obtained by supramolecular aggregation followed by ionic
melt polycondensation (IMP) using melamine and 2,4,6-triaminopyrimidine as a
dopant. The solid state NMR spectrum of (15)N-enriched CN confirms the triazine
as a building unit. Controlling the amount and arrangements of dopants in the CN
structure can dramatically enhance the photocatalytic performance for H2
evolution. The polytriazine imide (PTI) exhibits the apparent quantum efficiency
(AQE) of 15% at 400 nm. This method successfully enables a substantial amount of
visible light to be harvested for H2 evolution, and provides a promising route
for the rational design of a variety of highly active crystalline CN
photocatalysts.
PMID- 25124193
TI - Implications of the Wnt5a/CaMKII pathway in retinoic acid-induced myogenic tongue
abnormalities of developing mice.
AB - Although proper tongue development is relevant to other structures in the
craniofacial region, the molecular details of muscle development in tongue remain
poorly understood. Here, we report that pregnant mice treated with retinoic acid
(+RA) produce embryos with tongue malformation and a cleft palate. Histological
analyses revealed that at E14.5, the tongues of +RA fetuses failed to descend and
flatten. Ultrastructural analysis showed that at perinatal stage E18.5, the
myofilaments failed to form normal structures of sarcomeres, and arranged
disorderly in the genioglossus. The proliferation and levels of myogenic
determination markers (Myf5 and MyoD) and myosin in the genioglossus were
profoundly reduced. Wnt5a and Camk2d expressions were down-regulated, while
levels of Tbx1, Ror2, and PKCdelta were up-regulated in the tongues of +RA
fetuses. In mock- and Wnt5a-transfected C2C12 (Wnt5a-C2C12) cells, Wnt5a
overexpression impaired proliferation, and maintained Myf5 at a relative high
level after RA treatment. Furthermore, Wnt5a overexpression positively correlated
with levels of Camk2d and Ror2 in C2C12 cells after RA exposure. These data
support the hypothesis that the Wnt5a/CaMKII pathway is directly involved in RA
induced hypoplasia and disorder of tongue muscles.
PMID- 25124196
TI - [Prevalence of uterine fibroids in France and impact on quality of life: results
of a survey among 2500 women between 30-55 years].
AB - OBJECTIVES: To evaluate the prevalence of symptomatic uterine fibroid in France,
related symptoms and its impact on quality of life. MATERIALS AND METHODS: Online
prospective survey from December 2012 to February 2013 using two questionnaires
on 2498 women aged between 30 and 55 years old and representatives of the
feminine population. RESULTS: On the studied population, 220 women presented a
symptomatic uterine fibroid representing a prevalence of 8.8%. 163 women (73.7%)
presented bleedings associated or not with pain, and 58 (26.3%) suffered from
pain only. For 77 (34.9%) women, the symptoms preceded the diagnostic and the
mean delay between first symptoms and diagnostic was 2.22 years (ET : 3.56). At
the time of the survey, 144 (65%) women with symptomatic uterine fibroid were
followed by a physician (a gynecologist in 91.6% (n=132)), and 110 (49.7%)
evaluated their pain as severe or extremely severe and 178 (80.6%) were bothered
by their symptoms in their everyday life. CONCLUSION: This analysis shows a
strong prevalence for symptomatic uterine fibroid with a major impact on the
quality of life.
PMID- 25124197
TI - Score test variable screening.
AB - Variable screening has emerged as a crucial first step in the analysis of high
throughput data, but existing procedures can be computationally cumbersome,
difficult to justify theoretically, or inapplicable to certain types of analyses.
Motivated by a high-dimensional censored quantile regression problem in multiple
myeloma genomics, this article makes three contributions. First, we establish a
score test-based screening framework, which is widely applicable, extremely
computationally efficient, and relatively simple to justify. Secondly, we propose
a resampling-based procedure for selecting the number of variables to retain
after screening according to the principle of reproducibility. Finally, we
propose a new iterative score test screening method which is closely related to
sparse regression. In simulations we apply our methods to four different
regression models and show that they can outperform existing procedures. We also
apply score test screening to an analysis of gene expression data from multiple
myeloma patients using a censored quantile regression model to identify high-risk
genes.
PMID- 25124198
TI - Rapid separation and characterization of diterpenoid alkaloids in processed roots
of Aconitum carmichaeli using ultra high performance liquid chromatography
coupled with hybrid linear ion trap-Orbitrap tandem mass spectrometry.
AB - The lateral root of Aconitum carmichaeli, a popular traditional Chinese medicine,
has been widely used to treat rheumatic diseases. For decades, diterpenoid
alkaloids have dominated the phytochemical and biomedical research on this plant.
In this study, a rapid and sensitive method based on ultra high performance
liquid chromatography coupled with linear ion trap-Orbitrap tandem mass
spectrometry was developed to characterize the diterpenoid alkaloids in Aconitum
carmichaeli. Based on an optimized chromatographic condition, more than 120
diterpenoid alkaloids were separated with good resolution. Using a systematic
strategy that combines high resolution separation, highly accurate mass
measurements and a good understanding of the diagnostic fragment-based
fragmentation patterns, these diterpenoid alkaloids were identified or
tentatively identified. The identification of these chemicals provided essential
data for further phytochemical studies and toxicity research of Aconitum
carmichaeli. Moreover, the ultra high performance liquid chromatography with
linear ion trap-Orbitrap mass spectrometry platform was an effective and accurate
tool for rapid qualitative analysis of secondary metabolite productions from
natural resources.
PMID- 25124200
TI - Adolescent health care maintenance in a teen-friendly clinic.
AB - Adolescence is marked by complex physical, cognitive, social, and emotional
development, which can be stressful for families and adolescents. Before the
onset of puberty, providers should clearly lay the groundwork for clinical care
and office visits during the adolescent years. This article addresses the
guidelines and current legal standards for confidentiality in adolescent care,
the most frequently used psychosocial screening tools, and current
recommendations for preventive health services and immunizations. Through the
creation of teen-friendly clinics, primary care providers are well positioned to
offer guidance and support to teens and their parents during this time of
transition and growth.
PMID- 25124199
TI - Knowing who to trust: exploring the role of 'ethical metadata' in mediating risk
of harm in collaborative genomics research in Africa.
AB - BACKGROUND: The practice of making datasets publicly available for use by the
wider scientific community has become firmly integrated in genomic science. One
significant gap in literature around data sharing concerns how it impacts on
scientists' ability to preserve values and ethical standards that form an
essential component of scientific collaborations. We conducted a qualitative
sociological study examining the potential for harm to ethnic groups, and
implications of such ethical concerns for data sharing. We focused our empirical
work on the MalariaGEN Consortium, one of the first international collaborative
genomics research projects in Africa. METHODS: We conducted a study in three
MalariaGEN project sites in Kenya, the Gambia, and the United Kingdom. The study
entailed analysis of project documents and 49 semi-structured interviews with
fieldworkers, researchers and ethics committee members. RESULTS: Concerns about
how best to address the potential for harm to ethnic groups in MalariaGEN
crystallised in discussions about the development of a data sharing policy.
Particularly concerning for researchers was how best to manage the sharing of
genomic data outside of the original collaboration. Within MalariaGEN, genomic
data is accompanied by information about the locations of sample collection, the
limitations of consent and ethics approval, and the values and relations that
accompanied sample collection. For interviewees, this information and context
were of important ethical value in safeguarding against harmful uses of data, but
is not customarily shared with secondary data users. This challenged the ability
of primary researchers to protect against harmful uses of 'their' data.
CONCLUSION: We identified three protective mechanisms--trust, the existence of a
shared morality, and detailed contextual understanding--which together might play
an important role in preventing the use of genomic data in ways that could harm
the ethnic groups included in the study. We suggest that the current practice of
sharing of datasets as isolated objects rather than as embedded within a
particular scientific culture, without regard for the normative context within
which samples were collected, may cause ethical tensions to emerge that could
have been prevented or addressed had the 'ethical metadata' that accompanies
genomic data also been shared.
PMID- 25124201
TI - Adolescent growth and development.
AB - Adolescence is a developmental stage defined by physical and psychosocial
maturation. This article reviews normal pubertal development and the evaluation
and management of adolescents with suspected pubertal abnormalities and provides
an overview of adolescent psychosocial development.
PMID- 25124202
TI - Parents and family matter: strategies for developing family-centered adolescent
care within primary care practices.
AB - Healthy adolescent development and successful transition to adulthood begins in
the family. Supporting families in their communities and cultures ultimately
makes this support system stronger. Parenting adolescents is described as the
most challenging life stage for parents. Primary care providers are in an ideal
position to support families with teens. This article reviews stressors,
recommends strength-based strategies, describes how health care delivery systems
can be organized to address the needs of adolescents and their families, shares a
case study of a family-oriented, youth-friendly primary care clinic, and provides
practical strategies for developing family-centered adolescent care within
primary care practices.
PMID- 25124203
TI - Primary care for adolescents with developmental disabilities.
AB - Disability is a natural part of the human experience. To maximize potential,
adolescents with disabilities require multidisciplinary transition planning and
life-skill training. Health care professionals can reduce barriers to accessing
health care. They can encourage self-determination and connect patients to self
advocacy organizations. They can facilitate smooth transitions to adult health
care services. Careful descriptions of a patient's baseline traits and function
are critical, not only to assist in person centered planning processes, but to
ensure that new caregivers and clinicians have the information they need to
recognize changes in function or behavior that can signal illness.
PMID- 25124204
TI - Body image and health: eating disorders and obesity.
AB - Eating behavior in adolescents can be as high risk as other behaviors that arise
during this period and can have serious health consequences. This article
presents a framework for screening and treatment of abnormal adolescent eating
behavior by the primary care provider. A review of the types of disordered eating
is presented along with suggested ways to screen. Indications for subspecialty
eating disorder referrals and key aspects of screening and intervention in
adolescent obesity and eating disorders are also reviewed. Specific attention is
paid to the aspects of care that can be provided in primary care and
multidisciplinary care.
PMID- 25124206
TI - Teens, technology, and health care.
AB - Teens are avid users of new technologies and social media. Nearly 95% of US
adolescents are online at least occasionally. Health care professionals and
organizations that work with teens should identify online health information that
is both accurate and teen friendly. Early studies indicate that some of the new
health technology tools are acceptable to teens, particularly texting, computer
based psychosocial screening, and online interventions. Technology is being used
to provide sexual health education, medication reminders for contraception, and
information on locally available health care services. This article reviews early
and emerging studies of technology use to promote teen health.
PMID- 25124205
TI - Common issues encountered in adolescent sports medicine: guide to completing the
preparticipation physical evaluation.
AB - Participation in athletic activities among children and adolescents is on the
rise in the United States. Approximately 35 million children ages 5 to 18 play
organized sports each year. High school athletes suffer approximately 2 million
injuries per year, resulting in 500,000 doctor visits and 30,000
hospitalizations. In addition, early specialization in sports has led to
increased incidence of overuse injury in adolescents. Head injuries among
adolescents are also on the rise. Primary care providers are called on to
complete preparticipation evaluations and to see adolescents with acute injuries.
The goal of this article is to discuss these issues common to adolescent
athletes.
PMID- 25124207
TI - Adolescent substance involvement use and abuse.
AB - Substance use in adolescence is common, but not all use indicates a substance use
disorder. The primary care provider has an essential role in screening for
substance involvement, assessing the level of substance use and its impact on
function, and engaging in a brief intervention to encourage and support
behavioral change related to substance use. This article summarizes the
literature on adolescent vulnerability to substance use disorders and their
impact on adolescent health and well-being. Practical concrete suggestions for
approaches to screening, brief interventions, and referral to treatment provide a
stepwise approach to adolescent substance use assessment and intervention.
PMID- 25124208
TI - Mood disorders in adolescents: diagnosis, treatment, and suicide assessment in
the primary care setting.
AB - The primary care setting is considered the entry point of adolescents with mental
illness in the health care system. This article informs primary care providers
about the diagnostic features and differential of mood disorders in adolescents,
screening and assessment, as well as evidence-based psychosocial and
psychopharmacologic therapies. The article also provides a framework for decision
making regarding initiating treatment in the primary care setting and referral to
mental health services. Furthermore, the article highlights the importance of the
collaboration between primary care and mental health providers to facilitate
engagement of adolescents with mood disorders and adherence to treatment.
PMID- 25124209
TI - Adolescent pregnancy and contraception.
AB - 7% of US teen women became pregnant in 2008, totaling 750,000 pregnancies
nationwide. For women ages 15 to 19, 82% of pregnancies are unintended.
Adolescents have a disproportionate risk of medical complications in pregnancy.
Furthermore, adolescent parents and their infants both tend to suffer poor
psychosocial outcomes. Preventing unintended and adolescent pregnancies are key
public health objectives for Healthy People 2020. Screening for sexual activity
and pregnancy risk should be a routine part of all adolescent visits. Proven
reductions in unintended pregnancy in teens are attained by providing access to
contraception at no cost and promoting the most-effective methods.
PMID- 25124210
TI - Common sexually transmitted infections in adolescents.
AB - Adolescents are often at higher risk for acquiring sexually transmitted
infections (STIs). Medical providers should be alert for both asymptomatic and
symptomatic STIs, and follow appropriate screening guidelines. Moreover,
providers need to know how to best administer adolescent-friendly confidential
care, treatment, and health education in the primary care setting. This article
addresses the most common adolescent STIs and pertinent recommendations for
screening, diagnosis, and management of infections, in addition to a brief
focused discussion on human immunodeficiency virus and adolescents.
PMID- 25124211
TI - Sexual minority youth.
AB - This article provides an overview of the medical and mental health needs of the
lesbian, gay, bisexual, and transgender (LGBT) youth population. Information is
reviewed regarding both primary medical care and the special health risks that
these youth face. Providers are introduced to the concept that societal and
internalized homophobia lead directly to certain health disparities, including
substance use, school and family rejection, depression, and increased sexually
transmitted infection acquisition. This article familiarizes the primary care
practitioner with the health care needs of the LGBT population and the research
behind the various recommendations for caring for these youth.
PMID- 25124212
TI - Adolescent interpersonal violence: implications for health care professionals.
AB - Violence involvement is a leading cause of morbidity and mortality among
adolescents. This review provides a summary of the burden of adolescent violence
and violence-related behavior, risk, and protective factors for violence
outcomes. The importance of screening for violence involvement in the primary
care setting and examples of online resources to support providers in advocating,
assessing, and intervening on behalf of youth are also reviewed. The article
draws attention to bullying and dating/relationship violence, not as new forms of
violence-related behavior, but as behaviors with health outcomes that have
recently received increased attention.
PMID- 25124213
TI - Health care for youth involved with the correctional system.
AB - Adolescents with involvement in the correctional system have significant health
risks and needs. Professional guidelines and policies related to health services
in correctional settings can help health care providers who work in youth
detention facilities and those who see youth for follow-up care after
incarceration. Several challenges exist to providing care in detention
facilities, but overcoming these barriers to optimally serve youth is critical.
When youth are released to their homes, community providers must understand the
extent of care offered in detention facilities, the unique considerations for
youth on probation, and the aspects of follow-up care that should be addressed.
PMID- 25124214
TI - Know your audience. Adolescent medicine.
PMID- 25124215
TI - Adolescent medicine. Preface.
PMID- 25124216
TI - Axial level-specific regulation of neuronal development: lessons from PITX2.
AB - Transcriptional regulation of gene expression is vital for proper control of
proliferation, migration, differentiation, and survival of developing neurons.
Pitx2 encodes a homeodomain transcription factor that is highly expressed in the
developing and adult mammalian brain. In humans, mutations in PITX2 result in
Rieger syndrome, characterized by defects in the development of the eyes,
umbilicus, and teeth and variable abnormalities in the brain, including
hydrocephalus and cerebellar hypoplasia. Alternative splicing of Pitx2 in the
mouse results in three isoforms, Pitx2a, Pitx2b, and Pitx2c, each of which is
expressed symmetrically along the left-right axis of the brain throughout
development. Here, we review recent evidence for axial and brain region-specific
requirements for Pitx2 during neuronal migration and differentiation,
highlighting known isoform contributions.
PMID- 25124217
TI - The ontogenetic origins of skull shape disparity in the Triturus cristatus group.
AB - Comparative studies of ontogenies of closely related species provide insights
into the mechanisms responsible for morphological diversification. Using
geometric morphometrics, we investigated the ontogenetic dynamics of postlarval
skull shape and disparity in three closely related crested newt species. The
skull shapes of juveniles just after metamorphosis (hereafter metamorphs) and
adult individuals were sampled by landmark configurations that describe the shape
of the dorsal and ventral side of the newt skull, and analyzed separately. The
three species differ in skull size and shape in metamorphs and adults. The
ontogenies of dorsal and ventral skull differ in the orientation but not lengths
of the ontogenetic trajectories. The disparity of dorsal skull shape increases
over ontogeny, but that of ventral skull shape does not. Thus, modifications of
ontogenetic trajectories can, but need not, increase the disparity of shape. In
species with biphasic life-cycles, when ontogenetic trajectories for one stage
can be decoupled from those of another, increases and decreases in disparity are
feasible, but our results show that they need not occur.
PMID- 25124218
TI - Cardiac magnetic resonance versus transthoracic echocardiography for the
assessment and quantification of aortic regurgitation in patients undergoing
transcatheter aortic valve implantation.
AB - BACKGROUND: The transthoracic echocardiographic (TTE) evaluation of the severity
of residual aortic regurgitation (AR) following transcatheter aortic valve
implantation (TAVI) has been controversial and lacks validation. OBJECTIVES: This
study sought to compare TTE and cardiac magnetic resonance (CMR) for assessment
of AR in patients undergoing TAVI with a balloon-expandable valve. METHODS: TTE
and CMR exams were performed pre-TAVI in 50 patients and were repeated
postprocedure in 42 patients. All imaging data were analysed in centralised core
laboratories. RESULTS: The severity of native AR as determined by multiparametric
TTE approach correlated well with the regurgitant volume and regurgitant fraction
determined by CMR prior to TAVI (Rs=0.79 and 0.80, respectively; p<0.001 for
both). However, after TAVI, the correlation between the prosthetic AR severity
assessed by TTE and regurgitant volume and fraction measured by CMR was only
modest (Rs=0.59 and 0.59, respectively; p<0.001 for both), with an
underestimation of AR severity by TTE in 61.9% of patients (1 grade in 59.5%).
The TTE jet diameter in parasternal view and the multiparametric approach
(Rs=0.62 and 0.59, respectively; both with p<0.001) showed the best correlation
with CMR regurgitant fraction post-TAVI. The circumferential extent of prosthetic
paravalvular regurgitation showed a poor correlation with CMR regurgitant volume
and fraction (Rs=0.32, p=0.084; Rs=0.36, p=0.054, respectively). CONCLUSIONS: The
severity of AR following TAVI with a balloon-expandable valve was underestimated
by echocardiography as compared with CMR. The jet diameter, but not the
circumferential extent of the leaks, and the multiparametric echocardiography
integrative approach best correlated with CMR findings. These results provide
important insight into the evaluation of AR severity post-TAVI.
PMID- 25124219
TI - Age-related differences in the activity of arterial mineral deposition and
regional bone metabolism: a 18F-sodium fluoride positron emission tomography
study.
AB - Functional (18)F-fluoride PET demonstrated an inverse relationship between the
activity of arterial mineral deposition and regional bone metabolism. While bone
metabolism decreases with age, the activity of arterial mineral deposition
increases. INTRODUCTION: The extent of arterial calcification increases with age,
whereas bone mineral density decreases, evidencing a well-known inverse
correlation on morphological basis. The aim of this study was to evaluate the
functional relationship between the activity of arterial mineral deposition and
regional bone metabolism as assessed by (18)F-sodium fluoride (NaF) PET/CT.
METHODS: Three hundred four subjects were examined by (18)F-NaF PET/CT. Tracer
accumulation in the femoral arteries was analyzed both qualitatively and
semiquantitatively by measuring the blood-pool-corrected standardized uptake
value (target-to-background ratio). Uptake was compared with cardiovascular risk
factors (RFs), calcified plaque burden, and regional bone metabolism as assessed
by PET/CT. RESULTS: The activity of arterial mineral deposition significantly
increased with age (p < 0.001), whereas regional bone metabolism significantly
decreased (p < 0.001). There was a significant inverse correlation between bone
metabolism and arterial mineral deposition (unadjusted, p < 0.001); that
association was not significant (p = 0.79) when controlled for age and other RFs.
Both high activity of arterial mineral deposition and low bone metabolism were
significantly associated with cardiovascular events and other RFs. CONCLUSION:
(18)F-NaF PET/CT provides a tool to visualize and quantify the activity of
arterial mineral deposition and regional bone metabolism. In this study, we
observed an inverse correlation between the activity of arterial mineral
deposition and regional bone metabolism. While the activity of arterial mineral
deposition significantly increases with age, regional bone metabolism decreases.
PMID- 25124220
TI - Utility of an Australasian registry for children undergoing radiation treatment.
AB - INTRODUCTION: The aim of this study was to evaluate the utility of an
Australasian registry ('the Registry') for children undergoing radiation
treatment (RT). METHODS: Children under the age of 16 years who received a course
of radiation between January 1997 and December 2010 and were enrolled on the
Registry form the subjects of this study. RESULTS: A total of 2232 courses of RT
were delivered, predominantly with radical intent (87%). Registrations fluctuated
over time, but around one-half of children diagnosed with cancer undergo a course
of RT. The most prevalent age range at time of RT was 10-15 years, and the most
common diagnoses were central nervous system tumours (34%) and acute
lymphoblastic leukaemia (20%). CONCLUSIONS: The Registry provides a reflection of
the patterns of care of children undergoing RT in Australia and a mechanism for
determining the resources necessary to manage children by RT (human, facilities
and emerging technologies, such as proton therapy). It lacks the detail to
provide information on radiotherapy quality and disease outcomes which should be
the subject of separate audit studies. The utility of the Registry has been
hampered by its voluntary nature and varying needs for consent. Completion of
registry forms is a logical requirement for inclusion in the definition of a
subspecialist in paediatric radiation oncology.
PMID- 25124221
TI - Site-directed delivery of nitric oxide to cancers.
AB - Nitric oxide (NO) is a reactive gaseous free radical which mediates numerous
biological processes. At elevated levels, NO is found to be toxic to cancers and
hence, a number of strategies for site-directed delivery of NO to cancers are in
development during the past two decades. More recently, the focus of research has
been to, in conjunction with other cancer drugs deliver NO to cancers for its
secondary effects including inhibition of cellular drug efflux pumps. Among the
various approaches toward site-selective delivery of exogenous NO sources, enzyme
activated nitric oxide donors belonging to the diazeniumdiolate category afford
unique advantages including exquisite control of rates of NO generation and
selectivity of NO production. For this prodrug approach, enzymes including
esterase, glutathione/glutathione S-transferase, DT-diaphorase, and
nitroreductase are utilized. Here, we review the design and development of
various approaches to enzymatic site-directed delivery of NO to cancers and their
potential.
PMID- 25124224
TI - Ocular pterygium--digital keloid dysplasia.
AB - We describe an adolescent Peruvian male with marked, aggressive ingrowth of
conjunctiva (pterygium-like) over the cornea associated with keloid formation on
his distal limbs. He has in addition camptodactyly of all fingers and to some
extent of his toes, and unusual skin pigmentations. He resembles an earlier
described family from Norway in which a mother and two children showed a similar
combination of signs. We present the follow-up of the Norwegian family. The
entity resembles the Penttinen syndrome but can be differentiated due to the
early aging in the latter, which is lacking in the presently reported entity. We
suggest naming this entity ocular pterygium-digital keloid dysplasia. The
condition follows likely an autosomal dominant pattern of inheritance.
PMID- 25124225
TI - Molecularly imprinted polymer as in-line concentrator in capillary
electrophoresis coupled with mass spectrometry for the determination of
quinolones in bovine milk samples.
AB - In this work molecularly imprinted polymers have been evaluated as sorbent for
the construction of an in-line solid phase extraction analyte concentrator in
capillary electrophoresis coupled with mass spectrometry for the determination of
the eight regulated veterinary quinolones in bovine milk samples. Different
parameters affecting the analyte concentrator performance, such as sample pH,
volume and composition of the elution plug and injection time, were studied.
Sample volumes of 22MUL (2bar for 15min) were loaded on the MISPE microcartridge
and the retained analytes were eluted by injecting a plug of MeOH/H2O/NH3
(60/37/3 by volume) for 125s at 50mbar (60nL). The proposed method is simple for
the monitoring of these antibiotic residues in milk samples, allowing the direct
injection of the samples with minimum sample pretreatment, achieving limits of
detection between 3.8 and 4.7MUgkg(-1) and unequivocal identification of the
compounds working in tandem mass spectrometry. Recoveries ranging from 70.0 to
102.3% were obtained and satisfactory intra-day and inter-day RSDs were achieved
(<=12% and 15% respectively). Reproducibility among different constructed analyte
concentrators showed RSD<=11%.
PMID- 25124226
TI - Simultaneous determination of nickel, cobalt and mercury ions in water samples by
solid phase extraction using multiwalled carbon nanotubes as adsorbent after
chelating with sodium diethyldithiocarbamate prior to high performance liquid
chromatography.
AB - Multiwalled carbon nanotubes (MWNTs) have been widely used for the enrichment of
trace important pollutants in environment because of its large specific surface
area, high extraction efficiency, and easy operation. In this study, a solid
phase extraction method was established to determine nickel (Ni(2+)), cobalt
(Co(2+)) and mercury (Hg(2+)) ions using MWNTs as the adsorbent and sodium
diethyldithiocarbamate (DDTC) as the chelating agent. The final analysis was
performed on a high performance liquid chromatography (HPLC). The factors that
may influence the extraction efficiency were optimized in detail including the
type and volume of elution solvent, sample pH, volume of chelating agent
solution, and volume of sample solution, etc. The experimental results indicated
that good linear relationship between peak area and the concentration of the ions
was achieved in the range of 0.1-100MUgL(-1), 0.1-50MUgL(-1), and 2.7-300MUgL(-1)
for Ni(2+), Co(2+), and Hg(2+), respectively. The precision was determined by
calculating the relative standard deviation (R.S.D.) values that were in the
range of 6.2-11.7% under the optimal conditions. The detection limits of Ni(2+),
Co(2+), and Hg(2+) were in the range of 0.04-0.9MUgL(-1) (S/N=3). The presented
method was applied for the determination of the metal ions mentioned above in
real water samples, and satisfied results were achieved. All these indicated that
proposed method will be a good alternative tool for monitoring the target ions in
environmental samples in the future.
PMID- 25124227
TI - Ionic liquid-assisted liquid-phase microextraction based on the solidification of
floating organic droplets combined with high performance liquid chromatography
for the determination of benzoylurea insecticide in fruit juice.
AB - A green, simple, and efficient method, ionic liquid-assisted liquid-liquid
microextraction based on the solidification of floating organic droplets (ILSFOD
LLME) collected via a bell-shaped collection device (BSCD) coupled to high
performance liquid chromatography with a variable-wavelength detector, was
developed for the preconcentration and analysis of seven benzoylurea insecticides
(BUs) in fruit juice. In the proposed method, the low-density solvent 1-dodecanol
and the ionic liquid trihexyl(tetradecyl)phosphonium hexafluorophosphate ([P14,
6, 6, 6]PF6) were used as extractant. The extraction solvent droplet was easily
collected and separated by the BSCD without centrifugation. The experimental
parameters were optimized by the one-factor-at-a-time approach and were followed
using an orthogonal array design. The results indicated the different effects of
each parameter for extraction efficiency. Under the optimal conditions in the
water model, the limits of detection for the analytes varied from 0.03 to
0.28MUgL(-1). The enrichment factors ranged from 160 to 246. Linearities were
achieved for hexaflumuron and flufenoxuron in the range of 0.5-500MUgL(-1), for
triflumuron, lufenuron and diafenthiuron in the range of 1-500MUgL(-1), and for
diflubenzuron and chlorfluazuron in the range of 5-500MUgL(-1); the correlation
coefficients for the BUs ranged from 0.9960 to 0.9990 with recoveries of 75.6
113.9%. Finally, the developed technique was successfully applied to real fruit
juice with acceptable results. The relative standard deviations (RSDs) of the
seven BUs at two spiked levels (50 and 200MUgL(-1)) varied between 0.1% and 7.3%.
PMID- 25124228
TI - Determination of levamisole and tetramisole in seized cocaine samples by
enantioselective high-performance liquid chromatography and circular dichroism
detection.
AB - Levamisole, an anthelmintic drug, has been increasingly employed as an adulterant
of illicit street cocaine over the last decade; recently, the use of tetramisole,
the racemic mixture of levamisole and its enantiomer dexamisole, was also
occasionally observed. A new enantioselective high-performance liquid
chromatography (HPLC) method, performed on cellulose tris(3,5
dimethylphenylcarbamate) chiral stationary phases in normal-phase mode, was
validated to determine the enantiomeric composition of tetramisole enantiomers in
seized cocaine samples. Furthermore, the hyphenation of the validated HPLC method
with a circular dichroism (CD) detection system allowed the direct determination
of elution order and a selective monitoring of levamisole and dexamisole in the
presence of possible interferences. The method was applied to the identification
and quantitation of the two enantiomers of tetramisole in seized street cocaine
samples.
PMID- 25124229
TI - Chiral chromatography-tandem mass spectrometry applied to the determination of
pro-resolving lipid mediators.
AB - Pro-resolving lipid mediators are a class of endogenously synthesized molecules
derived from different fatty acids, such as arachidonic, docosahexaenoic or
eicosapentaenoic acid, which are derived into four different product families:
lipoxins, resolvins, maresins and protectins. For quantitation of these
compounds, a sensitive, selective and robust liquid chromatography-tandem mass
spectrometry method was developed and validated for the simultaneous quantitation
of lipoxin A4, 6-epi-lipoxin A4, lipoxin B4 and lipoxin A5, the D-series
resolvins D1 and D2 as well as aspirin-triggered lipoxin A4 and resolvin D1,
maresin and protectin and the pathway markers 17(S)-hydroxy-docosahexaenoic acid
and 17(R)-hydroxy-docosahexaenoic acid in cell culture supernatants. For this
purpose, a chiral column was connected in series with a reversed-phase column to
achieve efficient analyte separation and high sensitivity. Sample pre-treatment
included a fast and simple liquid-liquid extraction procedure. Limits of
quantitation in the range of 0.1-0.5ng/mL cell culture media, absolute recoveries
between 90 and 115%, intra- and interday precision of less than 13% and an
accuracy of less than 11% were obtained. Stability of the samples after 60 days
storage at -80 degrees C, three freeze/thaw cycles and 4h at room temperature has
been demonstrated for all analytes. Sample extracts can be stored at 7 degrees C
for 24h without degradation of the analytes. Deviations of less than 13% in the
accuracy, evaluated in terms of relative error, were obtained. The suitability of
the method has been demonstrated in cell culture supernatants of human
polymorphonuclear leukocytes, stimulated with 15R-hydroxy-eicosatetraenoic acid
and in cell culture media of human polymorphonuclear leukocytes co-incubated with
human platelets. From all studied analytes, lipoxin A4 and 6-epi-lipoxin A4 were
found in cell culture media under both incubation conditions, while 15-epi
lipoxin A4 was additionally detected in cell culture supernatants of
polymorphonuclear leukocytes stimulated with 15R-hydroxy-eicosatetraenoic acid.
PMID- 25124231
TI - Survival disparities between Maori and non-Maori men with prostate cancer in New
Zealand.
AB - OBJECTIVE: To examine temporal trends and current survival differences between
Maori and non-Maori men with prostate cancer in New Zealand (NZ). PATIENTS AND
METHODS: A cohort of 37,529 men aged >= 40 years diagnosed with prostate cancer
between 1996 and 2010 was identified from the New Zealand Cancer Registry and
followed until 25 May 2011. Cause of death was obtained from the Mortality
Collection by data linkage. Survival for Maori compared with non-Maori men was
estimated using the Kaplan-Meier method, and Cox proportional hazard regression
models, adjusted for age, year of diagnosis, socioeconomic deprivation and
rural/urban residence. RESULTS: The probability of surviving was significantly
lower for Maori compared with non-Maori men at 1, 5 and 10 years after diagnosis.
Maori men were more likely to die from any cause [adjusted hazard ratio (aHR)
1.84, 95% confidence interval (CI) 1.72-1.97] and from prostate cancer (aHR 1.94,
95% CI 1.76- 2.14). The aHR of prostate cancer death for Maori men diagnosed with
regional extent was 2.62-fold (95% CI 1.60-4.31) compared with non-Maori men. The
survival gap between Maori and non-Maori men has not changed throughout the study
period. CONCLUSION: Maori men had significantly poorer survival than non-Maori,
particularly when diagnosed with regional prostate cancer. Despite improvements
in survival for all men diagnosed after 2000, the survival gap between Maori and
non-Maori men has not been reduced with time. Differences in prostate cancer
detection and management, partly driven by higher socioeconomic deprivation in
Maori men, were identified as the most likely contributors to ethnic survival
disparities in NZ.
PMID- 25124232
TI - Equivalent input produces different output in the UniFrac significance test.
AB - BACKGROUND: UniFrac is a well-known tool for comparing microbial communities and
assessing statistically significant differences between communities. In this
paper we identify a discrepancy in the UniFrac methodology that causes
semantically equivalent inputs to produce different outputs in tests of
statistical significance. RESULTS: The phylogenetic trees that are input into
UniFrac may or may not contain abundance counts. An isomorphic transform can be
defined that will convert trees between these two formats without altering the
semantic meaning of the trees. UniFrac produces different outputs for these
equivalent forms of the same input tree. This is illustrated using metagenomics
data from a lake sediment study. CONCLUSIONS: Results from the UniFrac tool can
vary greatly for the same input depending on the arbitrary choice of input
format. Practitioners should be aware of this issue and use the tool with caution
to ensure consistency and validity in their analyses. We provide a script to
transform inputs between equivalent formats to help researchers achieve this
consistency.
PMID- 25124233
TI - Simulations of potentials of mean force for separating a leucine zipper dimer and
the basic region of a basic region leucine zipper dimer.
AB - Basic region leucine zipper (bZIP) transcription factors involved in DNA
recognition are dimeric proteins. The monomers consist of two subdomains, a
leucine zipper sequence responsible for dimerization and a highly basic DNA
recognition sequence. Leucine zippers are strongly dimerized, and in a bZIP, the
basic region can, in the absence of DNA, undergo extensive relative monomer-to
monomer fluctuations. In this work, LZ and bZIP potentials of mean force (PMFs),
which provide free energies along reaction coordinates, are simulated with a
distance replica exchange method. The method uses restraint potentials to provide
sampling along a reaction coordinate and enhances configuration space exploration
by exchanging information between neighboring restraint potential configurations.
Restraint potentials that are constructed from sums over a number of atom
distances are employed. Their use requires a modification of the Weighted
Histogram Analysis Method (WHAM) procedure to combine and unbias the data from
the different restraint-potential-biased window densities to provide a PMF. These
methods are first used to obtain a PMF for separating a leucine zipper (GCN4-p1)
of the yeast transcriptional activator GCN4. The PMF indicates a very strong
binding free energy that only weakens when the monomers are separated by about 12
A, which is about 6 A beyond their bound, dimer equilibrium distance. PMFs are
also obtained for separating the basic subdomain monomer parts of the GCN4 bZIP
transcriptional factor, in the absence of DNA. In a monomer separation range
spanning the open, crystal-based structure to closer configurations, the basic
subdomain PMF is quite flat, implying essentially thermal sampling in this
distance range. A PMF generated starting from a "collapsed" state, taken from a
previous simulation ( J. Phys. Chem. B 2012 , 116 , 6071 ), where collapsed
refers to the feature that the basic subdomain monomers are also effectively
dimerized, shows that this state is bound in free energy, though much less so
than the leucine zipper dimer.
PMID- 25124230
TI - A study on the mechanism by which MDMA protects against dopaminergic dysfunction
after minimal traumatic brain injury (mTBI) in mice.
AB - Driving under methylenedioxymethamphetamine (MDMA) influence increases the risk
of being involved in a car accident, which in turn can lead to traumatic brain
injury. The behavioral deficits after traumatic brain injury (TBI) are closely
connected to dopamine pathway dysregulation. We have previously demonstrated in
mice that low MDMA doses prior to mTBI can lead to better performances in
cognitive tests. The purpose of this study was to assess in mice the changes in
the dopamine system that occurs after both MDMA and minimal traumatic brain
injury (mTBI). Experimental mTBI was induced using a concussive head trauma
device. One hour before injury, animals were subjected to MDMA. Administration of
MDMA before injury normalized the alterations in tyrosine hydroxylase (TH) levels
that were observed in mTBI mice. This normalization was also able to lower the
elevated dopamine receptor type 2 (D2) levels observed after mTBI. Brain-derived
neurotrophic factor (BDNF) levels did not change following injury alone, but in
mice subjected to MDMA and mTBI, significant elevations were observed. In the
behavioral tests, haloperidol reversed the neuroprotection seen when MDMA was
administered prior to injury. Altered catecholamine synthesis and high D2
receptor levels contribute to cognitive dysfunction, and strategies to normalize
TH signaling and D2 levels may provide relief for the deficits observed after
injury. Pretreatment with MDMA kept TH and D2 receptor at normal levels, allowing
regular dopamine system activity. While the beneficial effect we observe was due
to a dangerous recreational drug, understanding the alterations in dopamine and
the mechanism of dysfunction at a cellular level can lead to legal therapies and
potential candidates for clinical use.
PMID- 25124234
TI - MOF-derived porous ZnO/ZnFe2O4/C octahedra with hollow interiors for high-rate
lithium-ion batteries.
AB - Novel porous ZnO/ZnFe2O4/C octahedra with hollow interiors are fabricated by a
facile self-sacrificing template method involving the refluxing synthesis of
hollow, metal-organic framework octahedra in solution and subsequent thermal
annealing in N2 . When evaluated as an anode material for lithium-ion batteries,
these porous hollow ZnO/ZnFe2O4/C octahedra exhibit significantly enhanced
electrochemical performances with high rate capability, high capacity, and
excellent cycling stability.
PMID- 25124235
TI - The significance of circulating tumour cells in breast cancer: a review.
AB - Haematogenous spread of circulating tumour cells (CTCs) is the principle
mechanism for development of metastases. Research into the enumeration and
characterisation of CTCs, particularly in the last decade, has allowed the
introduction of semi-automated CTC assessment in the clinical setting. In breast
cancer, CTC enumeration is being used as a prognostic biomarker, a predictive
biomarker of treatment response and is being assessed to guide treatment in both
the early and metastatic setting. CTC characterisation has the potential to
direct targeted therapies, such as HER2 therapies in HER2 negative primary breast
tumour patients. However, CTC assessment has considerable challenges. Capture and
identification of these very rare cells is currently largely dependent on a
presumed homogeneity of phenotype. In addition, high throughput assays are
lacking. The clinical significance of CTCs is incompletely understood. A large
proportion of CTC positive patients have no evidence of metastases, raising the
issue of either inconsequential tumour dormancy or non-viable CTCs. CTCs may have
additional clinical sequelae such as promoting venous thrombosis. However CTCs
provide a real-time liquid biopsy of the tumour and represent an exciting,
minimally invasive method of assessing disease status and also a novel
therapeutic target for malignancy.
PMID- 25124236
TI - The net clinical benefit of personalized antiplatelet therapy in patients
undergoing percutaneous coronary intervention.
AB - This was a prospective study comparing two groups: personalized and non
personalized treatment with P2Y12 receptor blockers during a 12-month follow-up.
We aimed to investigate whether personalized antiplatelet treatment in patients
with high on-treatment platelet reactivity (HTPR) improves clinical outcome.
Platelet reactivity was assessed by adenosine diphosphate induced aggregation
using a multiple electrode aggregometry (MEA) in 798 patients with coronary
artery disease undergoing percutaneous coronary intervention (PCI). Patients with
HTPR received up to four repeated loading doses of clopidogrel or prasugrel in
the personalized treatment group (n=403), whereas no change in the treatment
strategy was undertaken in patients with HTPR in the non-personalized treatment
group (n=395). There were fewer major adverse cardiac events (MACE) in the
personalized treatment group than in the non-personalized treatment group (7.4%
compared with 15.3% respectively; P<0.001). The multivariate Cox regression
analysis showed that the relative risk to develop MACE was 51% lower in the
personalized treatment group as compared with the non-personalized treatment
group [hazard ratio (HR)=0.49; 95% confidence interval (CI): 0.31-0.77; P<0.001].
Similarly, there was a clear net benefit of the personalized antiplatelet
treatment over the non-personalized treatment (ischemic and bleedings events:
8.2% versus 18.7% respectively; HR=0.46; 95%CI: 0.29-0.70; P<0.001). Further
analysis indicated that patients with aggregation values within the therapeutic
window (21-49 units) experienced the lowest event rates (stent thrombosis and
major bleeding: 2.5%) as compared with poor responders (>=50 units: 5.4%) or
ultra-responders (0-20 units: 5.2%). In conclusion, personalized antiplatelet
treatment might improve patients' outcome without increasing bleeding
complications compared with the non-personalized treatment during a 12-month
follow-up.
PMID- 25124237
TI - Impact of the quadrivalent HPV vaccine on disease recurrence in men exposed to
HPV Infection: a randomized study.
AB - INTRODUCTION: Human papillomavirus (HPV) is one of the most common sexually
transmitted infections and is the cause of several different diseases in men and
women. Although little is known about HPV infection in men, they are also in the
risk group of HPV infection and play an important role in transmitting the virus
to women. AIM: To define the efficacy of the HPV vaccine through cross
immunization and its role in clearance of HPV infection, and to assess infection
associated factors in men. METHODS: This prospective randomized clinical study
enrolled 171 evaluable men with genital warts between June 2009 and October 2013.
After the initial treatment intervention, 91 patients were randomly assigned to
receive HPV vaccine in three doses. Eighty patients were in the control
(unvaccinated) group. One hundred-eleven men were single and 60 men were married.
Patients who had previous treatment for pre-existing warts and medical disorders
that needed chronic treatment or immunosuppression were not included in the
randomization. Also 29 men with follow-up less than 12 months and incomplete
vaccination were not included. MAIN OUTCOME MEASURES: The patients were assessed
regarding age, condom use, marital status, number of visible genital warts, and
smoking status. Post-treatment follow-up was monthly up to 12th month. RESULTS:
Mean age was 34 +/- 7.6. One hundred fifteen patients were smokers. For the
recurrence of warts, age, smoking, vaccination status were insignificant and
marital status was significant in the univariable analysis; only marital status
preserved significance (HR: 2.0 CI:1.29-3.12 P = 0.002) in the multivariable
analysis including vaccination status, marital status, and smoking. CONCLUSION:
Among the investigated factors vaccination status was not but marital status
significantly influenced wart recurrence. Married men had more recurrences in our
population. Larger multicenter randomized clinical trials are lacking and
seriously required to investigate the therapeutic effect of current quadrivalent
HPV vaccine in genital warts.
PMID- 25124238
TI - Pregnancy does not increase the local recurrence rate after surgical resection of
desmoid-type fibromatosis.
AB - BACKGROUND: Pregnancy has been reported as a risk factor for promoting growth and
progression of desmoid-type fibromatosis because of the presumed role of
estrogens in stimulating desmoid growth. In this study, the clinical outcomes of
females who were pregnant 5 years or less before resection of desmoid tumor or
who became pregnant after resection were compared to nulliparous females or
females who were pregnant more than 5 years before resection. METHODS: Obstetric
histories of desmoid tumor patients were abstracted from medical records.
Patients were grouped by pregnancy status as either: pregnancy-associated
(pregnant up to 5 years before primary desmoid tumor resection or pregnant after
resection) or not pregnancy-associated (nulliparous or pregnant more than 5 years
before resection of desmoid tumor). Cox proportional hazards regression was used
to evaluate pregnancy status as a predictor of desmoid tumor recurrence. RESULTS:
There were 15 females who had pregnancy-associated desmoids (33%) and 31 females
who had non-pregnancy-associated desmoids (67%). There were no differences in
clinicopathologic features or recurrence-free survival between females of
different pregnancy status in univariate or multivariate survival analyses.
CONCLUSION: Recurrence-free survival rates among women recently pregnant before
or pregnant after resection of desmoid tumor and nulliparous women or those with
a remote history of pregnancy are comparable after adjusting for patient age,
anatomic location, and completeness of surgical resection. Subsequent pregnancy
should not be discouraged for reproductive-aged women after resection of desmoid
type fibromatosis.
PMID- 25124239
TI - A combinatorial approach towards water-stable metal-organic frameworks for highly
efficient carbon dioxide separation.
AB - A library of 20 UiO-66-derived metal-organic frameworks (MOFs) is synthesized in
a combinatorial approach involving mixed ligand copolymerization and two post
synthetic modifications (PSMs) in tandem. Mixed ligand co-polymerization of
benzene-1,4-dicarboxylic acid (BDC) and sodium 2-sulfoterephthalate (SS-BDC) with
zirconium tetrachloride (ZrCl4 ) was used to prepare 5 groups of MOFs with the
same UiO-66 topology but differing amounts of sulfate groups. These MOFs exhibit
excellent water stabilities in a pH range of 1 to 12, together with high CO2
uptake capacities and selectivities.
PMID- 25124240
TI - The state of epidemiological knowledge in the 21st century.
PMID- 25124241
TI - [Disease transmission dynamics according to complexity theory].
AB - OBJECTIVE: Illustrating disease transmission as a complex system according to
complexity theory. METHODS: A SIR mathematical model (S=number susceptible,
I=number infectious, and R=number recovered or immune) reflecting disease
transmission from the connection between states of susceptibility, infection,
disease, recovery and nonlinearity in the interaction between susceptible and
infected was simulated. Infection rate temporal fluctuations were described by
logistic mapping. RESULTS: Transmission occurs with the reduction of susceptible
states as people become infected and sick, followed by an increase in
individuals' recovery following diagnosis and treatment. Small increases in
infection rate value led to fluctuations in the number of susceptible and exposed
people and randomness in the relationship between being susceptible and infected,
until converging towards a regular pattern. CONCLUSION: The model reflected the
connection between states of susceptibility, nonlinearity and chaotic behavior
following small increases in infection rate. A historical and trans-disciplinary
perspective could help in understanding transmission complexity and coordinating
control options.
PMID- 25124242
TI - [The contribution of epidemiology to disease control: malaria].
AB - Despite the number of cases and attributable mortality having become reduced,
malaria continues to be an important public health problem. This report presents
some examples of epidemiology's contribution to malaria control; it also
motivates reflexion to the contrary, i.e. malaria's contribution to the
development of epidemiology. Attempting to identify methods for measuring
epidemiology's contribution to malaria control led to an in-depth analysis of
what exactly does epidemiology consist of, whether all its contributions could be
considered positive and to what extent they might have been due just to
epidemiology.
PMID- 25124244
TI - [The role of research-based evidence in health system policy decision-making].
AB - Different models may be used for explaining how research-based evidence is used
in healthcare system policy-making. It is argued that models arising from a
clinical setting (i.e. evidence-based policy-making model) could be useful
regarding some types of healthcare system decision-making. However, such models
are "silent" concerning the influence of political contextual factors on
healthcare policy-making and are thus inconsistent with decision-making regarding
the modification of healthcare system arrangements. Other political science-based
models would seem to be more useful for understanding that research is just one
factor affecting decision-making and that different types of research-based
evidence can be used instrumentally, conceptual or strategically during different
policy-making stages.
PMID- 25124243
TI - [Colombian experience regarding skin cancer: healthcare-related barriers to
access to healthcare and bureaucratic itineraries].
AB - OBJECTIVES: Describing and understanding the experiences of people suffering non
melanoma skin cancer in their struggles to recuperate, deciphering their
itinerary regarding their health-seeking behavior, describing the relationship
between patients and the Colombian healthcare system by referring to the number
of pertinent writs and the percentage of denied services, and documenting the
determinants which are related to timely diagnosis. METHODS: This was a mixed
methods study, combining epidemiology and critical medical anthropology; the
study involved a retrospective cohort of 369 people, 3 focus groups including 48
participants and in-depth interviews regarding 20 cases. RESULTS: The data
revealed specific healthcare system-related barriers to access to healthcare,
intermediate barriers (work-related and geographical) and structural barriers
(economic-, income-, purchasing power-, social cohesion- and education-related).
Timely diagnosis was made in 32.5% of the reported cases. Related determinants
consisted of educational level equal to or above technical training (OR 4.4),
home ownership (OR 4.8), living in an urban area (OR3.5) and contributory regime
affiliation (OR 1.9); 28% of the people involved in the study reported that they
had been denied access to a service (biopsy, surgery) and the rate of resorting
to legal means (i.e. writs) was 5 out of every 100 new cases per year. The
itinerary from the time of the appearance of a particular disease to definitive
resolution was established. DISCUSSION: People living in unfavorable social
conditions were involved in the severest cases and, paradoxically, faced the
largest set of barriers to access to healthcare in Colombia. Such barriers extend
beyond the healthcare system and will not become resolved solely through
healthcare reform.
PMID- 25124245
TI - [Evidence-based public health decision-making tools which can also be used for
prioritising disease].
AB - He use of research-based evidence has been promoted during recent years, due to
the increasing development of evidence-based medicine,and it has been reported
that transferring the concept of "evidence-based" from clinical to public health
practice has not been as straight forward as expected.Much research-based
evidence for supporting public health recommendations has come from studies whose
evidence has been qualified as being low or very low quality in the medical
hierarchy based on classic evidence and the grading of recommendations,
assessment, development and evaluation (GRADE)approach. This paper was aimed at
presenting two methods of rating evidence, as well as their limitations and
applications as public health decision-making tools.
PMID- 25124246
TI - [The background, development and perspectives of modern epidemiology].
AB - Epidemiology is an ongoing discipline (i.e. still being constructed) and many of
the foundations of the theory and methods now in use were mostly developed during
the second half of the twentieth century, arising from what is known today as
"modern epidemiology". This paper summary the history and main ideas which guided
epidemiology at that time, the debates and divisions that characterized such
advance and presents a "biased" point of view concerning the perspectives which
could help thinking about the disciplinary development of epidemiology.
PMID- 25124247
TI - [A Latin-American perspective regarding the past, present and future of
epidemiology].
AB - This article addresses three questions. Concerning the past, why was there no pre
Columbian epidemiology? What are the origins of modern epidemiology (including
its South American roots)? A surrealistic title has been chosen regarding the
future to emphasise the fact that making predictions is not easy. Why are complex
phenomena the dark object of epidemiological desire?
PMID- 25124248
TI - [Latin-American public policy regarding social determinants of health].
AB - The study was aimed at identifying Latin-American countries' public policy which
has been related to the social determinants of health. A topic review was thus
made of papers kept in the 22 Latin-American countries' databases and official
documents issued by their multilateral organisations and ministries of health.
The World Health Organization's concept of the social determinants of health has
been summarised and a history given of the pertinent work developed worldwide in
regions such as Europe and Latin-America. Public policy regarding the field of
study in Argentina, Brazil, Bolivia, Chile, Colombia, Costa Rica, Mexico and
Venezuela has been described. It was concluded that Latin-America provides a
panorama of inequality regarding the application of policy concerning the social
determinants of health and that there was segmented intervention, mainly
regarding intermediate determinants of health, without taking an integrated
approach from different entrance points into account, according to the stated
conceptual framework.
PMID- 25124249
TI - [Ascertaining a Venezuelan oil town's health conditions].
AB - Objective Analysing health conditions in the town of Carirubana in Falcon State,
Venezuela, as a prior study to the construction of a gas conditioning plant
there. Methods This study formed part of a field research project which involved
consulting primary and secondary sources. The former consisted of evaluating
public and private health-centres and those in the Barrio Adentro system; the
aforementioned health centres' medical staff were interviewed to determine
current health-disease status and the factors determining health for the town
being studied. Likewise, both situations (health-disease and factors determining
health) were evaluated and analysed in the secondary sources at national, state
and municipal level. Results Deficits were observed at national level regarding
public health infrastructure; there were 1.3 beds per thousand inhabitants, this
being less than half that recommended by the World Health Organization (WHO)
(i.e. three to four beds per thousand inhabitants). State and municipal cancer
mortality rates were relatively stable over a four-year period (2001-2004).
Conclusions The mortality rate in Carirubana was characteristic of a low-income
area. The poverty and pollution directly produced by the oil refining plants were
the key determinants for this town's morbidity and mortality rates.
PMID- 25124251
TI - [An occupational evaluation of disabled people from a human abilities'
viewpoint].
AB - OBJECTIVE: Describing how a tool was designed for assessing disabled people in
Colombia (called "Occupational evaluation of handicapped people in Colombia").
METHOD: This was a multi-method study which consisted of five phases and a
stakeholder participation-based strategy. The first stage of the multi-method
research involved a literature review followed by expert judgment and then peer
assessment of the tool; the fourth stage involved a pilot study and and a basic
training course in occupational assessment involved the tool's socialisation with
actors working in the field of occupational assessment, taking their suggestions
into account for final adjustment of the tool. RESULTS: A tool was developed for
the occupational assessment of disabled people in Colombia which was based on
identifying their capabilities in terms of performance and general work skills to
promote their inclusion in the workforce. CONCLUSIONS: Considering the Colombian
state's responsibility for ensuring disabled people's right to work and their
inclusion in the workforce (Law 1346/2009, Law 1618/2013 and Convention on the
Rights of People with Disabilities (CRPD)), this tool will not replace existing
ones but will promote a more favourable perception of disabled people, thereby
facilitating their inclusion in the workforce.
PMID- 25124250
TI - [A study concerning how much weight schoolchildren carry in their bags, involving
four schools in the metropolitan area of Buenos Aires, Argentina].
AB - OBJECTIVE: Determining the weight children carry in their bags to school
(absolute and relative values) and the distance walked during home-school routes,
involving students from four schools in the metropolitan area of Buenos Aires.
METHOD: The study involved 751 primary (4th to 6th grades) and secondary (1st to
3rd years) level students who were attending three private schools and one public
one. Body and bag weights were measured and the children were asked about the
distance (in blocks) they walked from school to home. The study involved a
descriptive analysis and contrasted the students by gender, educational level,
type of school and grade or year. Possible associations between variables were
ascertained. The group was divided into those carrying bags weighing less than
10% of their body weight and those who carrying 10% (considered a critical value)
and more; frequencies were calculated by the type of bag being used. RESULTS: 68%
of the sample were carrying 10% or more of their body weight (P42=10.13%): 66% in
male (P44=10.12%) and 60% in female children (P40=10.2%). Private school students
carried more weight than public school children (p<0.05) and younger students
carried a greater weight than older students (p<0.05) in both educational levels.
CONCLUSIONS: Most children were carrying relative weights well above that
recommended and female students were most affected. Younger students carried
higher absolute and relative weights.
PMID- 25124252
TI - [The characterization of biosolids produced by the San Fernando wastewater
treatment plant in Itagui, Antioquia, Colombia].
AB - ABSTRACT Objective This study was aimed at evaluating pertinent physicochemical
and microbiological (bacteria and parasites) parameters regarding the biosolids
produced by the San Fernando wastewater treatment plant (WWTP) in Itagui,
Antioquia, Colombia. Methods Twelve samples were collected and evaluated every
month from January to December during 2010. The chemical, physical and
microbiological tests followed the protocol described in Colombian technical
guideline 5167. The protocol described in Mexican official Norm 004 (with some
modifications) was used for identifying helminth ova and assessing their
viability. Results All samples proved positive for Ascarislumbricoides, viable
ova count ranging from 4 to 22 eggs/2gTS. Both Salmonella and Enterobacteriawere
detected in all samples evaluated, the latter having 3,000 colony forming unit
(CFU)/g minimum concentration. Biosolid sample values met the heavy metal
concentration requirement established by national guidelines. There was no
statistical association between rainfall and the pathogen's presence in the
biosolids. Conclusion Our results suggested that the biosolids being produced by
the San Fernando wastewater treatment plant (WWTP) could be used as organic
fertilizer; however they should be treated/sanitized to meet the stipulations in
Colombian technical guideline 5167.
PMID- 25124253
TI - Comparison of pre- and post-operative health-related quality of life and length
of stay after primary total hip replacement in matched English and German patient
cohorts.
AB - PURPOSE: We compare pre- and post-operative health-related quality of life
(HRQoL) and length of stay after total hip replacement (THR) in matched German
and English patient cohorts to test for differences in admission thresholds,
clinical effectiveness and resource utilisation between the healthcare systems.
METHODS: German data (n = 271) were collected in a large orthopaedic hospital in
Munich, Germany; English data (n = 26,254) were collected as part of the national
patient-reported outcome measures programme. HRQoL was measured using the EuroQoL
5D instrument. Propensity score matching was used to construct two patient
cohorts that are comparable in terms of preoperative patient characteristics.
RESULTS: Before matching, patients in England showed lower preoperative EQ-5D
scores (0.35 vs 0.52, p < 0.001) and experienced a larger improvement in HRQoL
(0.43 vs 0.33, p < 0.001) than German patients. Patients in the German cohort
were more likely to report no or only moderate problems with mobility and pain
preoperatively than their English counterparts. After matching, improvements in
HRQoL were comparable (0.32 vs 0.33, p = 0.638); post-operative scores were
slightly higher in the German cohort (0.82 vs 0.85, p = 0.585). Length of stay
was substantially lower in England than in Germany (4.5 vs 9.0 days, p < 0.001).
CONCLUSIONS: Our results highlight differences in preoperative health status
between countries, which may arise due to different admission thresholds and
access to surgery. In terms of quality of life, THR surgery is equally effective
in both countries when performed on similar patients, but hospital stay is
shorter in England.
PMID- 25124256
TI - Preparation of thermally stable microcapsules with a chitosan-silica hybrid.
AB - Addition of microcapsules with a high dielectric constant and low specific heat
capacity to a battered layer was designed to create a higher temperature in the
crust than in the prefried fish nuggets to prevent the water vapor in the fish
nuggets from migrating to the crust during microwave heating. Therefore, chitosan
silica hybrids and soybean oil were utilized to prepare the shell and core of the
thermally stable microcapsules (MC(CS)), respectively. The MC(CS) were prepared
by sol-gel coacervation from an oil-in-water emulsion. The sodium silicate was
hydrolyzed and coacervated through polymerization for 24 h at pH 5. The zeta
potential analysis indicated that chitosan with a positive charge and silica with
a negative charge interacted through electrostatic attraction to form a hybrid
shell. The volume mean particle size and encapsulation efficiency of the MC(CS)
were 9.6 +/- 0.2 MUm and 75.6% +/- 1.3%, respectively, when oil/chitosan = 0.2
and chitosan/silica = 0.5 (w/w). In addition to H-bonding and electrostatic
attraction, Si-O-N bonds were formed between chitosan and silica. Dehydration of
the bound water in the MC(CS) was observed in the range of 25 to 250 degrees C
in the differential scanning calorimetry thermal analysis, with the lack of
apparent thermal peaks indicating its high thermal stability. The decrease of
force to cut the crust observed by texture analysis as well as the increase of
hedonic score by consumer acceptance test revealed the addition of 1% MC(CS)
significantly improved the crispness of the crust in the microwave-reheated
nuggets.
PMID- 25124254
TI - Arginase activity in alternatively activated macrophages protects PI3Kp110delta
deficient mice from dextran sodium sulfate induced intestinal inflammation.
AB - Alternatively activated or M2 macrophages have been reported to protect mice from
intestinal inflammation, but the mechanism of protection has not been elucidated.
In this study, we demonstrate that mice deficient in the p110delta catalytic
subunit activity of class I phosphatidylinositol 3-kinase (PI3Kp110delta) have
increased clinical disease activity and histological damage during dextran sodium
sulfate (DSS) induced colitis. Increased disease severity in PI3Kp110delta
deficient mice is dependent on professional phagocytes and correlates with
reduced numbers of arginase I+ M2 macrophages in the colon and increased
production of inflammatory nitric oxide. We further demonstrate that
PI3Kp110delta-deficient macrophages are defective in their ability to induce
arginase I when skewed to an M2 phenotype with IL-4. Importantly, adoptive
transfer of IL-4-treated macrophages derived from WT mice, but not those from
PI3Kp110delta-deficient mice, protects mice during DSS-induced colitis. Moreover,
M2 macrophages mediated protection is lost when mice are cotreated with
inhibitors that block arginase activity or during adoptive transfer of arginase I
deficient M2 macrophages. Taken together, our data demonstrate that arginase I
activity is required for M2 macrophages mediated protection during DSS-induced
colitis in PI3Kp110delta-deficient mice.
PMID- 25124255
TI - Rare benign tumours of the nipple.
AB - BACKGROUND: Benign lesions of the breast in total are much more frequent than
malignant ones. However, there are no epidemiologic data on the prevalence of
benign or malignant tumours of the nipple, and the bibliography on benign nipple
tumours in general is limited. AIMS: To present some rare cases of benign nipple
tumours and review the literature. MATERIALS AND METHODS: Four cases of rare
benign nipple tumours: neurofibromas, wart, leiomyoma and milium are presented.
The literature search on benign nipple tumours was performed using MEDLINE,
Pubmed, and Cochrane databases with limits: English language, human species and
available abstract. The keyword used was 'benign nipple tumours'. RESULTS: The
initial search retrieved 337 articles. The papers were reviewed and the articles
that referred to benign lesions that appeared at the nipple specifically were
identified. Different entities that were described included: neurofibroma,
leiomyoma, milium, florid papillomatosis, syringomatous adenoma, nevoid
hyperkeratosis, fibroma, pseudolymphoma and haemangioma. DISCUSSION: Differential
diagnosis of benign tumours of the nipple can be demanding for the physicians.
Many of the symptoms and signs like pruritus, serosanguinous discharge,
lichenification, erosion and nodular enlargement are produced by either malignant
or benign nipple lesions. Radiology can be unclear in the diagnosis of nipple
abnormalities. CONCLUSION: Histological examination of the lesion can be the only
definite answer in these cases.
PMID- 25124257
TI - A therapeutic workplace for the long-term treatment of drug addiction and
unemployment: eight-year outcomes of a social business intervention.
AB - This study evaluated the long-term effects of a therapeutic workplace social
business on drug abstinence and employment. Pregnant and postpartum women (N =
40) enrolled in methadone treatment were randomly assigned to a therapeutic
workplace or usual care control group. Therapeutic workplace participants could
work weekdays in training and then as employees of a social business, but were
required to provide drug-free urine samples to work and maintain maximum pay.
Three-year outcomes were reported previously. This paper reports 4- to 8-year
outcomes. During year 4 when the business was open, therapeutic workplace
participants provided significantly more cocaine- and opiate-negative urine
samples than controls; reported more days employed, higher employment income, and
less money spent on drugs. During the 3 years after the business closed,
therapeutic workplace participants only reported higher income than controls. A
therapeutic workplace social business can maintain long-term abstinence and
employment, but additional intervention may be required to sustain effects.
PMID- 25124258
TI - Injection and sexual HIV/HCV risk behaviors associated with nonmedical use of
prescription opioids among young adults in New York City.
AB - Prevalence of nonmedical prescription opioid (PO) use has increased markedly in
the U.S. This qualitative study explores the drug-use and sexual experiences of
nonmedical PO users as they relate to risk for HIV and HCV transmission. Forty
six New York City young adult nonmedical PO users (ages 18-32) completed in
depth, semi-structured interviews. Despite initial perceptions of POs as less
addictive and safer than illegal drugs, PO misuse often led to long-term opioid
dependence and transition to heroin use and drug injection. Injectors in the
sample reported sporadic syringe-sharing, frequent sharing of non-syringe
injection paraphernalia and selective sharing with fellow injectors who are
presumed "clean" (uninfected). Participants reported little knowledge of HCV
injection-related risks and safer injection practices. They also reported
engaging in unprotected sex with casual partners, exchange sex and group sex, and
that PO misuse increases the risk of sexual violence. Prevention efforts
addressing HIV/HCV risk should be targeted to young nonmedical PO users.
PMID- 25124260
TI - The clustering of psychopathology among adults seeking treatment for alcohol and
drug addiction.
AB - Beyond the high prevalence of co-occurring mental and substance use disorders,
little is known about more complex patterns of psychopathology and
multimorbidity, particularly in treatment populations. We sought to identify a
parsimonious set of latent classes to describe the structure of mental disorder
comorbidity among adults entering outpatient addiction treatment, and explore
differences in the structure and prevalence of classes across sociodemographic
characteristics. Participants (N=544) completed the Psychiatric Diagnostic
Screening Questionnaire at treatment admission. We used latent class analysis to
identify classes of clients with specific patterns of co-occurring mental
disorders. The best-fitting solution identified 3 classes, characterized by no
comorbidity (i.e., substance use disorders only), co-occurring major depression,
and multimorbidity or a high degree of psychopathology. Older age was associated
with lower probability of being in the class with co-occurring major depression,
women were more likely than men to be in the multimorbid class, and being married
or partnered was associated with a lower probability of being in either of the
comorbid classes. These results are consistent with general population research
on the patterning of psychiatric disorders, implying that while clients in
addiction treatment may have extraordinarily high levels of psychopathology, the
patterns of symptoms and the groups most affected are not markedly different than
in other settings. By capturing the complexity of interrelationships among the
many factors that are known to influence prognosis and outcomes, latent class
analysis offers a useful way to examine and represent case-mix in clinical
populations.
PMID- 25124262
TI - Comment on: "Current status and trends in performance-based risk-sharing
arrangements between healthcare payers and medical product manufacturers".
PMID- 25124259
TI - Do improvements in substance use and mental health symptoms during treatment
translate to long-term outcomes in the opposite domain?
AB - Providers who treat adolescents with co-occurring substance use and mental health
issues may prioritize treatment of one set of symptoms believing that
improvements in one domain will result in improvements of the other. However,
limited empirical data for adolescents provide evidence of such "spillover
effects." Using data from 2900 youth in an outpatient treatment, we examined
whether during-treatment changes in substance use or mental health symptoms
predicted 12-month outcomes in the analogous and opposite domains. There was very
little evidence of spillover effects, only that youth with no internal distress
at 0 and 3 months reported lower levels of substance use problems at 12-months
relative to youth with internal distress that stayed the same from 0 to 3 months.
These findings suggest that providers treat both sets of substance use and mental
health symptoms in an integrated manner given that these symptoms commonly co
occur among youth with either set.
PMID- 25124261
TI - The influence of treatment attendance on subsequent aggression among severely
mentally ill substance abusers.
AB - The interrelationships between severe mental illness, substance use, and
aggression are of longstanding importance with implications for community
treatment programs, treatment research and public policy. Through the analysis of
longitudinal data collected from 278 patients over a 6-month period following
admission to an outpatient dual diagnosis treatment program, this study examined
the association between dual diagnosis treatment attendance and subsequent
aggression among individuals diagnosed with both a severe mental illness and a
substance use disorder. We also tested substance use and psychiatric symptoms as
mediators of this treatment-aggression relationship. The results of structural
equation modeling analyses indicated that dual diagnosis treatment was associated
with lower levels of subsequent aggression. Mediational analyses indicated that
greater treatment involvement was associated with reduced substance use, which
was associated with lower levels of aggression; thus, substance use was found to
mediate the relationship between dual diagnosis treatment and aggression.
Surprisingly, severity of psychiatric symptoms did not predict later aggression.
These findings suggest that targeting substance use reduction in treatment may
have the additional benefit of reducing the risk of later aggression among dual
diagnosis patients.
PMID- 25124263
TI - Authors' reply to Curto and Garattini: "Current status and trends in performance
based risk-sharing arrangements between healthcare payers and medical product
manufacturers".
PMID- 25124264
TI - Clinical outcomes in cytomegalovirus-positive Posner-Schlossman syndrome patients
treated with topical ganciclovir therapy.
AB - PURPOSE: To evaluate the clinical characteristics and therapeutic outcomes of
cytomegalovirus (CMV)-positive Posner-Schlossman syndrome patients undergoing
topical ganciclovir treatment. DESIGN: Retrospective, comparative, and
interventional case series. METHODS: One eye of each of 126 consecutive Posner
Schlossman syndrome patients was investigated using aqueous polymerase chain
reaction (PCR) between January 2006 and June 2013. The initial presentations and
follow-up data of the CMV-positive patients (68 eyes) and CMV-negative patients
(58 eyes) were compared. RESULTS: Severe endothelial cell loss (P < .001) and a
higher number of eyes requiring glaucoma filtering surgery (P = .017) were
observed in CMV-positive Posner-Schlossman syndrome patients. All CMV-infected
eyes treated with continual topical 2% ganciclovir exhibited an undetectable CMV
level at the following taps. During follow-up, the average number of
antiglaucomatous agents decreased, and a similar frequency of intraocular
pressure (IOP) spikes was observed in both groups (P = .358). Patients with CMV
positive eyes with a disease duration over 5 years were likely to require
glaucoma surgery (P = .024, log-rank test). All patients receiving surgery
exhibited CMV-negative PCR during the IOP attack, but experienced severe
peripheral anterior synechiae and pigment clogging. Both groups exhibited a
similar endothelial cell decrease (P = .243) and probability of progressive
endothelial cell loss (P = .219, log-rank test). CONCLUSION: Ganciclovir
treatment was effective for clearing the viral load, assisting the IOP control,
and preserving the corneal endothelium of CMV-positive Posner-Schlossman syndrome
patients. Early diagnosis and proper treatment could decrease the risk of
advanced glaucoma and avoid glaucoma surgery in long-lasting cases.
PMID- 25124265
TI - Dome-shaped macular configuration: longitudinal changes in the sclera and choroid
by swept-source optical coherence tomography over two years.
AB - PURPOSE: To study longitudinal changes in the posterior pole in eyes with dome
shaped macular configuration within the staphyloma. DESIGN: Prospective,
longitudinal study. METHODS: We prospectively examined the macular area in 35
eyes (26 patients) with dome-shaped macular configuration and high myopia (mean
spherical equivalent, -14.83 +/- 4.50 diopters) using swept-source optical
coherence tomography. Scleral and choroidal thicknesses were measured at the
fovea and at 4 parafoveal locations 2000 MUm from the foveal center. Height of
the macular bulge was measured as well. RESULTS: During the mean follow-up of
24.8 +/- 2.5 months, the scleral thickness significantly decreased at the fovea
from 496.1 +/- 95.7 MUm to 484.7 +/- 96.2 MUm (P < .001) and at all 4 parafoveal
locations (P < .001, respectively). The scleral thinning was asymmetric, with an
estimated decrease per year of 5.6 MUm at the foveal center, 11.1 MUm superiorly,
12.1 MUm inferiorly, 10.4 MUm temporally, and 5.8 MUm nasally. The ocular
concavities deepened over time, and mean macular bulge height increased from
136.5 +/- 60.9 MUm to 157.6 +/- 67.0 MUm (P < .001). The choroid within the
staphyloma showed generalized thinning during follow-up. Mean choroidal thickness
decreased significantly at the fovea from 28.3 +/- 17.2 MUm at baseline to 22.9
+/- 17.2 MUm (P < .001). CONCLUSIONS: Progressive asymmetric scleral thinning
occurred in the macular region of eyes with dome-shaped macular configuration.
The scleral thinning was more pronounced in the parafoveal area than at the
foveal center, resulting in an increase of the macular bulge height.
PMID- 25124266
TI - [Annular pancreas: a potentially overlooked congenital pancreatic anomaly].
PMID- 25124267
TI - South Africans with recent pregnancy rarely know partner's HIV serostatus:
implications for serodiscordant couples interventions.
AB - BACKGROUND: Implementation of safer conception strategies requires knowledge of
partner HIV-serostatus. We recruited women and men in a high HIV-prevalence
setting for a study to assess periconception risk behavior among individuals
reporting HIV-serodiscordant partnerships. We report screening data from that
study with the objective of estimating the proportion of individuals who are
aware that they are in an HIV-serodiscordant relationship at the time of
conception. METHODS: We screened women and men attending antenatal and
antiretroviral clinics in Durban, South Africa for enrollment in a study of
periconception risk behavior among individuals with serodiscordant partners.
Screening questionnaires assessed for study eligibility including age 18-45 years
(for women) or at least 18 years of age (for men), pregnancy in past year (women)
or partner pregnancy in the past 3 years (men), HIV status of partner for recent
pregnancy, participant's HIV status, and infected partner's HIV status having
been known before the referent pregnancy. RESULTS: Among 2620 women screened,
2344 (90%) met age and pregnancy criteria and knew who fathered the referent
pregnancy. Among those women, 963 (41%) did not know the pregnancy partner's HIV
serostatus at time of screening. Only 92 (4%) reported knowing of a
serodiscordant partnership prior to pregnancy. Among 1166 men screened, 225 (19%)
met age and pregnancy criteria. Among those men, 71 (32%) did not know the
pregnancy partner's HIV status and only 30 (13%) reported knowing of a
serodiscordant partnership prior to pregnancy. CONCLUSIONS: In an HIV-endemic
setting, awareness of partner HIV serostatus is rare. Innovative strategies to
increase HIV testing and disclosure are required to facilitate HIV prevention
interventions for serodiscordant couples.
PMID- 25124268
TI - Cardiovascular changes after administration of aerosolized salbutamol in horses:
five cases.
AB - Prevention and treatment of intraoperative hypoxemia in horses is difficult and
both efficacy and safety of therapeutic maneuvers have to be taken into account.
Inhaled salbutamol has been suggested as treatment of hypoxia in horses during
general anesthesia, due to safety and ease of the technique. The present report
describes the occurrence of clinically relevant unwanted cardiovascular effects
(i.e. tachycardia and blood pressure modifications) in 5 horses undergoing
general anesthesia in dorsal recumbency after salbutamol inhalation. Balanced
anesthesia based on inhalation of isoflurane in oxygen or oxygen and air and
continuous rate infusion (CRI) of lidocaine, romifidine, or combination of
lidocaine and guaifenesine and ketamine was provided. Supportive measures were
necessary to restore normal cardiovascular function in all horses but no long
term adverse effects were noticed in any of the cases.
PMID- 25124269
TI - Organic aerosols and inorganic species from post-harvest agricultural-waste
burning emissions over northern India: impact on mass absorption efficiency of
elemental carbon.
AB - Atmospheric PM2.5 (particulate matter with aerodynamic diameter of <= 2.5 MUm),
collected from a source region [Patiala: 30.2 degrees N; 76.3 degrees E; 250 m
above mean sea level] of emissions from post-harvest agricultural-waste (paddy
residue) burning in the Indo-Gangetic Plain (IGP), North India, has been studied
for its chemical composition and impact on regional atmospheric radiative
forcing. On average, organic aerosol mass accounts for 63% of PM2.5, whereas the
contribution of elemental carbon (EC) is ~3.5%. Sulphate, nitrate and ammonium
contribute up to ~85% of the total water-soluble inorganic species (WSIS), which
constitutes ~23% of PM2.5. The potassium-to-organic carbon ratio from paddy
residue burning emissions (KBB(+)/OC: 0.05 +/- 0.01) is quite similar to that
reported from Amazonian and Savanna forest-fires; whereas non-sea-salt-sulphate
to-OC ratio (nss-SO4(2-)/OC: 0.21) and nss-SO4(2-)/EC ratio of 2.6 are
significantly higher (by factor of 5 to 8). The mass absorption efficiency of EC
(3.8 +/- 1.3 m(2) g(-1)) shows significant decrease with a parallel increase in
the concentrations of organic aerosols and scattering species (sulphate and
nitrate). A cross plot of OC/EC and nss-SO4(2-)/EC ratios show distinct
differences for post-harvest burning emissions from paddy-residue as compared to
those from fossil-fuel combustion sources in south-east Asia.
PMID- 25124270
TI - Comparison of phloem and xylem hydraulic architecture in Picea abies stems.
AB - The hydraulic properties of xylem and phloem differ but the magnitude and
functional consequences of the differences are not well understood. Phloem and
xylem functional areas, hydraulic conduit diameters and conduit frequency along
the stems of Picea abies trees were measured and expressed as allometric
functions of stem diameter and distance from stem apex. Conductivities of phloem
and xylem were estimated from these scaling relations. Compared with xylem,
phloem conduits were smaller and occupied a slightly larger fraction of
conducting tissue area. Ten times more xylem than phloem was annually produced
along the stem. Scaling of the conduit diameters and cross-sectional areas with
stem diameter were very similar in phloem and xylem. Phloem and xylem conduits
scaled also similarly with distance from stem apex; widening downwards from the
tree top, and reaching a plateau near the base of the living crown. Phloem
conductivity was estimated to scale similarly to the conductivity of the
outermost xylem ring, with the ratio of phloem to xylem conductivity being c. 2%.
However, xylem conductivity was estimated to increase more than phloem
conductivity with increasing tree dimensions as a result of accumulation of xylem
sapwood. Phloem partly compensated for its smaller conducting area and narrower
conduits by having a slightly higher conduit frequency.
PMID- 25124271
TI - Effects of two different anesthetic protocols on cardiac flow measured by two
dimensional phase contrast magnetic resonance imaging.
AB - Companion animals are routinely anesthetized or heavily sedated for cardiac MRI
studies, however effects of varying anesthetic protocols on cardiac function
measurements are incompletely understood. The purpose of this prospective study
was to compare effects of two anesthetic protocols (Protocol A: Midazolam,
fentanyl; Protocol B: Dexmedetomidine) on quantitative and qualitative blood flow
values measured through the aortic, pulmonic, mitral, and tricuspid valves using
two-dimensional phase contrast magnetic resonance imaging (2D PC MRI) in healthy
dogs. Mean flow per heartbeat values through the pulmonary artery (Qp) and aorta
(Qs) were compared to right and left ventricular stroke volumes (RVSV, LVSV)
measured using a reference standard of 2D Cine balanced steady-state free
precession MRI. Pulmonary to systemic flow ratio (Qp/Qs) was also calculated.
Differences in flow and Qp/Qs values generated using 2D PC MRI did not differ
between the two anesthetic protocols (P = 1). Mean differences between Qp and
RVSV were 3.82 ml/beat (95% limits of agreement: 3.62, -11.26) and 1.9 ml/beat (
7.86, 11.66) for anesthesia protocols A and B, respectively. Mean differences
between Qs and LVSV were 1.65 ml/beat (-5.04, 8.34) and 0.03 ml/beat (-4.65,
4.72) for anesthesia protocols A and B, respectively. Mild tricuspid or mitral
reflux was seen in 2/10 dogs using 2D PC MRI. No aortic or pulmonic insufficiency
was observed. Findings from the current study indicated that these two anesthetic
protocols yield similar functional measures of cardiac blood flow using 2D PC MRI
in healthy dogs. Future studies in clinically affected patients are needed.
PMID- 25124272
TI - Closed-globe injuries of the ocular surface associated with combat blast
exposure.
AB - PURPOSE: To describe closed-globe conjunctival and corneal injuries and
endothelial cell abnormalities associated with blast exposure and their
relationships to other closed-globe injuries and blast-event characteristics.
DESIGN: Observational cross-sectional study. PARTICIPANTS: Veterans with a
history of blast-related traumatic brain injury (TBI). METHODS: History and
ocular examination, including slit-lamp biomicroscopy, gonioscopy, specular
microscopy. MAIN OUTCOME MEASURES: Type and location of blast injuries to the
conjunctiva and cornea. RESULTS: Ocular surface injuries were present in 25% (16
of 65) of blast-exposed veterans with TBI. Injuries included partial-thickness
anterior stromal corneal scars (15 eyes), Descemet membrane ruptures (6 eyes),
and conjunctival or corneal foreign bodies (7 eyes). Based on normative
information from an age-matched comparison group, endothelial cell abnormalities
were identified in 37% of participants. Eyes with ocular surface injury were more
likely to have lower endothelial cell density, higher coefficient of variation of
cell area, and lower percentage of hexagonal cells compared with eyes without
injury. Presence of ocular surface injury or endothelial cell abnormalities was
associated with elevated rates of other anterior and posterior segment injuries,
as well as impairment of visual acuity. We found no relationship between
ballistic eyewear use or severity level of TBI and presence of ocular surface
injuries from blast. CONCLUSIONS: Independent of TBI severity or use of
protective eyewear, ocular surface injuries and endothelial cell abnormalities
were found in significant numbers of veterans with blast-related brain injury.
Descemet membrane ruptures from blast exposure were described. Ocular surface
trauma was associated with other ocular injuries throughout the globe. Potential
mechanisms for the types and locations of ocular injuries seen were discussed.
Any corneal or conjunctival injury in a blast survivor should prompt a thorough
ocular trauma examination, including gonioscopy and specular microscopy, with
appropriate follow-up for associated injuries. Longitudinal studies are required
to determine long-term visual outcomes after blast exposure.
PMID- 25124274
TI - Stimulation of the subthalamic nucleus engages the cerebellum for motor function
in parkinsonian rats.
AB - Deep brain stimulation (DBS) is effective in managing motor symptoms of
Parkinson's disease in well-selected individuals. Recently, research has shown
that DBS in the basal ganglia (BG) can alter neural circuits beyond the
traditional basal ganglia-thalamus-cortical (BG-TH-CX) loop. For instance,
functional imaging showed alterations in cerebellar activity with DBS in the
subthalamic nucleus (STN). However, these imaging studies revealed very little
about how cell-specific cerebellar activity responds to STN stimulation or if
these changes contribute to its efficacy. In this study, we assess whether STN
DBS provides efficacy in managing motor symptoms in Parkinson's disease by
recruiting cerebellar activity. We do this by applying STN-DBS in
hemiparkinsonian rats and simultaneously recording neuronal activity from the
STN, brainstem and cerebellum. We found that STN neurons decreased spiking
activity by 55% during DBS (P = 0.038), which coincided with a decrease in most
pedunculopontine tegmental nucleus and Purkinje neurons by 29% (P < 0.001) and
28% (P = 0.003), respectively. In contrast, spike activity in the deep cerebellar
nuclei increased 45% during DBS (P < 0.001), which was likely from reduced
afferent activity of Purkinje cells. Then, we applied STN-DBS at sub-therapeutic
current along with stimulation of the deep cerebellar nuclei and found similar
improvement in forelimb akinesia as with therapeutic STN-DBS alone. This suggests
that STN-DBS can engage cerebellar activity to improve parkinsonian motor
symptoms. Our study is the first to describe how STN-DBS in Parkinson's disease
alters cerebellar activity using electrophysiology in vivo and reveal a potential
for stimulating the cerebellum to potentiate deep brain stimulation of the
subthalamic nucleus.
PMID- 25124275
TI - A web-based platform to support an evidence-based mental health intervention:
lessons from the CBITS web site.
AB - OBJECTIVE: To explore the role of Web-based platforms in behavioral health, the
study examined usage of a Web site for supporting training and implementation of
an evidence-based intervention. METHODS: Using data from an online registration
survey and Google Analytics, the investigators examined user characteristics and
Web site utilization. RESULTS: Site engagement was substantial across user
groups. Visit duration differed by registrants' characteristics. Less experienced
clinicians spent more time on the Web site. The training section accounted for
most page views across user groups. Individuals previously trained in the
Cognitive-Behavioral Intervention for Trauma in Schools intervention viewed more
implementation assistance and online community pages than did other user groups.
CONCLUSIONS: Web-based platforms have the potential to support training and
implementation of evidence-based interventions for clinicians of varying levels
of experience and may facilitate more rapid dissemination. Web-based platforms
may be promising for trauma-related interventions, because training and
implementation support should be readily available after a traumatic event.
PMID- 25124273
TI - Metabolism in HD: still a relevant mechanism?
AB - The polyglutamine expansion within huntingtin is the causative factor in the
pathogenesis of Huntington's disease (HD). Although the underlying mechanisms by
which mutant huntingtin causes neuronal dysfunction and degeneration have not
been fully elucidated, compelling evidence suggests that mitochondrial
dysfunction and compromised energy metabolism are key players in HD pathogenesis.
Longitudinal studies of HD subjects have shown reductions in glucose utilization
before the disease clinical onset. Preferential striatal neurodegeneration, a
hallmark of HD pathogenesis, also has been associated with interrupted energy
metabolism. Data from genetic HD models indicate that mutant huntingtin disrupts
mitochondrial bioenergetics and prevents adenosine triphosphate (ATP) generation,
implying altered energy metabolism as an important component of HD pathogenesis.
Here we revisit the evidence of abnormal energy metabolism in the central nervous
system of HD patients, review our current understanding of the molecular
mechanisms underlying abnormal metabolism induced by mutant huntingtin, and
discuss the promising therapeutic development by halting abnormal metabolism in
HD.
PMID- 25124277
TI - Quantification of polyphenols and evaluation of antimicrobial, analgesic and anti
inflammatory activities of aqueous and acetone-water extracts of Libidibia
ferrea, Parapiptadenia rigida and Psidium guajava.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Vast numbers of plant species from northeastern
Brazil have not yet been phytochemically or biologically evaluated. AIM OF THE
STUDY: The goal of this work was to obtain, characterize and show the
antimicrobial, analgesic and anti-inflammatory activities of aqueous and acetone
water extracts of Libidibia ferrea, Parapiptadenia rigida and Psidium guajava.
MATERIALS AND METHODS: The plant material (100g) was dried, and the crude
extracts were obtained by using turbo-extraction (10%; w/v) with water or
acetone:water (7:3, v/v) as the extraction solvent. High-performance liquid
chromatography (HPLC) methods were used to screen the crude extracts for
hydrolysable tannins (gallic acid) and condensed tannins (catechins). The
antibacterial activity was evaluated by agar-diffusion and microdilution methods
against Gram-positive strains (Staphylococcus aureus ATCC 25923, Staphylococcus
epidermidis INCQS 00016, Enterococcus faecalis ATCC 29212 and a clinical isolate
of methicillin-resistant Staphylococcus aureus) as well as Gram-negative strains
(Escherichia coli ATCC 25922, Salmonella enteritidis INCQS 00258, Shigella
flexneri and Klebsiella pneumoniae). To evaluate the anti-inflammatory activity,
a leukocyte migration model was used. Analgesic activity was determined by the
hot plate test and the acetic acid-induced abdominal writhing test. Data were
analyzed by analysis of variance (ANOVA) at a significance level of 5%. RESULTS:
Parapiptadenia rigida presented the highest amount of total polyphenols (35.82 +/
0.20%), while the greatest catechin content was found in the acetone-water
extract of Psidium guajava (EAWPg; 1.04 MUg/g). The largest amounts of catechins
were found in the aqueous extract of Libidibia ferrea (EALf; 1.07 MUg/g) and the
acetone-water extract of Parapiptadenia rigida (EAWPr; 1.0 MUg/g). All extracts
showed activity against Gram-positive bacteria. The aqueous and acetone-water
extracts of Psidium guajava showed the greatest inhibition zones in the agar
diffusion tests. In the evaluation of the minimum inhibitory concentration (MIC),
the most susceptible Gram-positive bacterium was Staphylococcus epidermidis and
the most susceptible Gram-negative bacterium was Shigella flexneri. EAPg and
EAWPg showed the greatest MIC values. All extracts were significant inhibitors of
leukocyte migration (p<0.05). Using the writhing test, significant analgesic
activity was found for EAPr (50 mg/kg), EAWPr (100 mg/kg and 200 mg/kg) and EAWPg
(50 mg/kg) (p<0.05). CONCLUSIONS: Thus, the appropriate extraction procedure
preserves the chemical components such as gallic acid and catechin, and showed
antimicrobial, anti-inflammatory and analgesic properties.
PMID- 25124276
TI - Attenuation of inflammatory mediators, oxidative stress and toxic risk evaluation
of Aporosa lindleyana Baill bark extract.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, Aporosa lindleyana Baill. has been
used against various ailments viz. jaundice, fever, headache, seminal loss and
insanity. The present study aims to evaluate the anti-inflammatory and anti
oxidant activity of the ethanolic extract of Aporosa lindleyana Baill. bark and
its fractions. METHOD: The anti-inflammatory activity of ethanolic extract of
Aporosa lindleyana Baill. bark and its various fractions at doses of 200mg/kg and
300mg/kg b.w. has been carried out by a carrageenan induced hind paw edema
method. To establish the probable mechanism of action, TNF-alpha and NO levels
have been estimated by an ELISA method and the effect of active fraction on COX-2
and NF-kappaB expressions has been evaluated. The effect on the levels of anti
oxidative enzymes (CAT, SOD & GPX) by the ethanolic extract and its fractions has
also been investigated. Furthermore, peptic ulcer and hepatotoxic risk evaluation
has also been carried out at three times higher dose than that used in
inflammatory in vivo model. RESULTS: Among the extract and its various fractions
tested for anti-inflammatory activity, the methanolic fraction at a dose of
300mg/kg showed significant inhibition in paw edema by 73% as compared to
Indomethacin which showed 77% inhibition after 5h. The same dose of methanolic
fraction also caused significant reduction in TNF-alpha (59.27%) and NO
concentration (57.12%) while Indomethacin showed inhibition of 63.91% and 60.12%.
The active methanolic fraction was also found to inhibit the expression of NF
kappaB and COX-2 induced by carrageenan. Histological studies showed that the
ethanolic extract and its fractions did not cause any damage to the stomach as
well as to liver. Moreover, the active fractions also decreased lipid
peroxidation levels and increased the antioxidant enzyme activities (SOD, CAT,
GPX). CONCLUSION: The results of present study demonstrated that significant anti
inflammatory activity of methanolic fraction of Aporosa lindleyana may be
attributed to the modulation of pro-inflammatory mediators. Same fraction was
also found to be effective against oxidative stress as it was found to elevate
the levels of anti-oxidative enzymes. It can therefore be concluded that the
methanolic fraction could be explored as a disease modifying agent against
inflammation and oxidative stress.
PMID- 25124278
TI - Expression of the vascular endothelial growth factor receptor system in porcine
oviducts after induction of ovulation and superovulation.
AB - This study was performed to determine the influence of insemination as well as
treatment with human chorionic gonadotropin (hCG) and equine chorionic
gonadotropin (eCG) on expression of the vascular endothelial growth factor (VEGF)
system in porcine oviducts. In the first experiment, 10 gilts were assigned to 2
groups: cyclic (treated with phosphate-buffered saline; n = 5) and inseminated (n
= 5). In experiment II, 15 gilts were assigned to 3 groups: inseminated (control;
n = 5), induced ovulation and inseminated (750 IU eCG, 500 IU hCG; n = 5), and
superovulated and inseminated (1500 IU eCG, 1000 IU hCG; n = 5). Oviducts
(isthmus and ampulla) were collected 3 days after phosphate-buffered saline
treatment (experiment I) or insemination. Blood samples were collected during
slaughter for E2 (estradiol) and P4 (progesterone) analysis. Levels of messenger
RNA (mRNA) of the VEGF system were analyzed by real-time polymerase chain
reaction and protein by Western blot and E2 and P4 using radioimmunoassays.
Insemination by itself decreased VEGF120 mRNA expression and VEGF-A protein level
in the oviductal isthmus (P < 0.05) but did not alter VEGF164 mRNA. Expression of
Flt-1 (c-fms-like tyrosine kinase VEGFR-1) mRNA increased in the isthmus of
inseminated relative to cyclic gilts (P < 0.05), whereas KDR (fetal liver kinase
1 VEGFR-2) mRNA levels decreased in both the oviductal isthmus (P < 0.05) and
ampulla (P < 0.001). Superovulation decreased VEGF120 and VEGF164 mRNA expression
in the isthmus compared with the inseminated group (P < 0.05), and lowered
protein levels of VEGF-A in the isthmus of both stimulated groups (P < 0.001).
Expression of Flt-1 mRNA was affected by hCG and eCG treatment in both
gonadotropin-stimulated groups in the isthmus as well as in the ampulla (P <
0.001) and protein levels in the ampulla of superovulated gilts (P < 0.05).
Protein levels of KDR were reduced in the oviductal ampulla of gilts in both the
induced ovulation and superovulated groups (P < 0.05). The concentrations of both
E2 and P4 increased significantly in superovulated group of gilts (P < 0.01 and P
< 0.05 for E2 and P4, respectively). Our study showed that insemination alone as
well as ovarian stimulation affected the mRNA and protein profiles of the VEGF
system in the porcine oviduct. Disrupted VEGF system expression may be crucial to
many events occurring during the periovulatory period and consequently could lead
to deprivation of VEGF-dependent factors that are necessary for proper
fertilization, gamete transport, and embryo development.
PMID- 25124280
TI - The cost-effectiveness of installing sidewalks to increase levels of transport
walking and health.
AB - OBJECTIVE: This study investigated the cost-effectiveness of installing sidewalks
to increase levels of transport-walking. METHODS: Secondary analysis using
logistic regression established the association of sidewalks with transport
walking using two transport-walking thresholds of 150 and 60 min/week using
Western Australian data (n=1394) from 1995 to 2000. Minimum, moderate and maximum
interventions were defined, associated respectively with one sidewalk, at least
one sidewalk and sidewalks on both sides of the street. Costs, average and
incremental cost-effectiveness ratios were calculated for each intervention and
expressed as 'the cost per person who walks for transport for more than 150
min/week (60 min/week) after the installation of new sidewalks'. A sensitivity
analysis examined the robustness of the incremental cost-effectiveness ratios to
varying model inputs. Costs are in 2012 Australian dollars. RESULTS: A positive
relationship was found between the presence of sidewalks and transport-walking
for both transport-walking thresholds of 150 and 60 min/week. The minimum
intervention was found to be the most cost-effective at $2330/person and
$674/person for the 150 and 60 min/week transport-walking thresholds
respectively. Increasing the proportion of people transport-walking and
increasing population density by 50% improved the cost-effectiveness of
installing side-walks to $346/person. CONCLUSIONS: To increase levels of
transport-walking, retrofitting streets with one sidewalk is most cost-effective.
PMID- 25124279
TI - Using electronic health record data to evaluate preventive service utilization
among uninsured safety net patients.
AB - OBJECTIVE: This study compared the preventive service utilization of uninsured
patients receiving care at Oregon community health centers (CHCs) in 2008 through
2011 with that of continuously insured patients at the same CHCs in the same
period, using electronic health record (EHR) data. METHODS: We performed a
retrospective cohort analysis, using logistic mixed effects regression modeling
to calculate odds ratios and rates of preventive service utilization for patients
without insurance, or with continuous insurance. RESULTS: CHCs provided many
preventive services to uninsured patients. Uninsured patients were less likely
than continuously insured patients to receive 5 of 11 preventive services,
ranging from OR 0.52 (95% CI: 0.35-0.77) for mammogram orders to 0.75 (95% CI:
0.66-0.86) for lipid panels. This disparity persisted even in patients who
visited the clinic regularly. CONCLUSION: Lack of insurance is a barrier to
preventive service utilization, even in patients who can access care at a CHC.
Policymakers in the United States should continue to address this significant
prevention disparity.
PMID- 25124281
TI - Online reports of foodborne illness capture foods implicated in official
foodborne outbreak reports.
AB - OBJECTIVE: Traditional surveillance systems capture only a fraction of the
estimated 48 million yearly cases of foodborne illness in the United States. We
assessed whether foodservice reviews on Yelp.com (a business review site) can be
used to support foodborne illness surveillance efforts. METHODS: We obtained
reviews from 2005 to 2012 of 5824 foodservice businesses closest to 29 colleges.
After extracting recent reviews describing episodes of foodborne illness, we
compared implicated foods to foods in outbreak reports from the U.S. Centers for
Disease Control and Prevention (CDC). RESULTS: Broadly, the distribution of
implicated foods across five categories was as follows: aquatic (16% Yelp, 12%
CDC), dairy-eggs (23% Yelp, 23% CDC), fruits-nuts (7% Yelp, 7% CDC), meat-poultry
(32% Yelp, 33% CDC), and vegetables (22% Yelp, 25% CDC). The distribution of
foods across 19 more specific food categories was also similar, with Spearman
correlations ranging from 0.60 to 0.85 for 2006-2011. The most implicated food
categories in both Yelp and CDC were beef, dairy, grains-beans, poultry and vine
stalk. CONCLUSIONS: Based on observations in this study and the increased usage
of social media, we posit that online illness reports could complement
traditional surveillance systems by providing near real-time information on
foodborne illnesses, implicated foods and locations.
PMID- 25124283
TI - Versatile iridicycle catalysts for highly efficient and chemoselective transfer
hydrogenation of carbonyl compounds in water.
AB - Cyclometalated iridium complexes are shown to be highly efficient and
chemoselective catalysts for the transfer hydrogenation of a wide range of
carbonyl groups with formic acid in water. Examples include alpha-substituted
ketones (alpha-ether, alpha-halo, alpha-hydroxy, alpha-amino, alpha-nitrile or
alpha-ester), alpha-keto esters, beta-keto esters and alpha,beta-unsaturated
aldehydes. The reduction was carried out at substrate/catalyst ratios of up to 50
000 at pH 4.5 and required no organic solvent. The protocol provides a practical,
easy and efficient way for the synthesis of beta-functionalised secondary
alcohols, such as beta-hydroxyethers, beta-hydroxyamines and beta-hydroxyhalo
compounds, which are valuable intermediates in pharmaceutical, fine chemical,
perfume and agrochemical synthesis.
PMID- 25124285
TI - Fungal surgical site infections.
PMID- 25124282
TI - Poly (ADP) ribose polymerase enzyme inhibitor, veliparib, potentiates
chemotherapy and radiation in vitro and in vivo in small cell lung cancer.
AB - Poly (ADP) ribose polymerase (PARP) plays a key role in DNA repair and is highly
expressed in small cell lung cancer (SCLC). We investigated the therapeutic
impact of PARP inhibition in SCLC. In vitro cytotoxicity of veliparib, cisplatin,
carboplatin, and etoposide singly and combined was determined by MTS in 9 SCLC
cell lines (H69, H128, H146, H526, H187, H209, DMS53, DMS153, and DMS114).
Subcutaneous xenografts in athymic nu/nu mice of H146 and H128 cells with
relatively high and low platinum sensitivity, respectively, were employed for in
vivo testing. Mechanisms of differential sensitivity of SCLC cell lines to PARP
inhibition were investigated by comparing protein and gene expression profiles of
the platinum sensitive and the less sensitive cell lines. Veliparib showed
limited single-agent cytotoxicity but selectively potentiated (>= 50% reduction
in IC50 ) cisplatin, carboplatin, and etoposide in vitro in five of nine SCLC
cell lines. Veliparib with cisplatin or etoposide or with both cisplatin and
etoposide showed greater delay in tumor growth than chemotherapy alone in H146
but not H128 xenografts. The potentiating effect of veliparib was associated with
in vitro cell line sensitivity to cisplatin (CC = 0.672; P = 0.048) and DNA-PKcs
protein modulation. Gene expression profiling identified differential expression
of a 5-gene panel (GLS, UBEC2, HACL1, MSI2, and LOC100129585) in cell lines with
relatively greater sensitivity to platinum and veliparib combination. Veliparib
potentiates standard cytotoxic agents against SCLC in a cell-specific manner.
This potentiation correlates with platinum sensitivity, DNA-PKcs expression and a
5-gene expression profile.
PMID- 25124284
TI - Clinical, lifestyle, socioeconomic determinants and rate of asymptomatic
intracranial atherosclerosis in stroke free Pakistanis.
AB - BACKGROUND: Intracranial Atherosclerotic Disease (ICAD) is the most frequent
etiology of stroke with high prevalence among Asians. Despite this, early
determinants of ICAD have not been described from this region. METHODS: The study
is an analytical prospective cross-sectional study of 200 adults from Radiology
Departments of two diagnostic centers in Karachi. Eligible participants confirmed
the absence of stroke symptoms via the Questionnaire for Verifying Stroke Free
Status (QVSFS) and underwent an interview covering medical, socio demographic,
lifestyle and anthropometric evaluation using locally validated and standardized
definitions. Magnetic Resonance Images (MRI) were centrally reviewed to detect
ICAD using the criterion used in the Warfarin-Aspirin Symptomatic Intracranial
Disease study. The risk factors associated with asymptomatic ICAD are reported
along with prevalence ratios. RESULTS: Of the 200 participants, ICAD was found in
34.5% (n = 69) of the participants. Mean age was 37.1 (S.D 15.1) years with 62%
younger than 45 years. Self-reported hypertension was found in 26.5% subjects,
diabetes in 9%, dyslipidemia in 5% and depression in 60%. Smokeless tobacco
(Adjusted PR 3.27 (1.07-6.05)), Western diet, high socioeconomic status (Adjusted
PR 2.26 (1.99-5.62)) and dyslipidemia (Adjusted PR 1.88 (1.25-2.21)) had
significant associations with ICAD after multivariable analysis. Age, gender,
diabetes, hypertension, depression and physical activity did not have a
significant association. CONCLUSION: ICAD was found on MRI in one in three
asymptomatic Pakistanis and was associated with modifiable risks. Initiatives
targeting primary prevention may be able to decrease the burden of disease caused
by stroke due to ICAD. STUDY REGISTRATION NUMBER: NCT02072876 2/25/2014.
PMID- 25124287
TI - Moving stem cell therapy to patients with idiopathic pulmonary fibrosis.
PMID- 25124286
TI - An image processing approach to analyze morphological features of microscopic
images of muscle fibers.
AB - We present an image processing approach to automatically analyze duo-channel
microscopic images of muscular fiber nuclei and cytoplasm. Nuclei and cytoplasm
play a critical role in determining the health and functioning of muscular fibers
as changes of nuclei and cytoplasm manifest in many diseases such as muscular
dystrophy and hypertrophy. Quantitative evaluation of muscle fiber nuclei and
cytoplasm thus is of great importance to researchers in musculoskeletal studies.
The proposed computational approach consists of steps of image processing to
segment and delineate cytoplasm and identify nuclei in two-channel images.
Morphological operations like skeletonization is applied to extract the length of
cytoplasm for quantification. We tested the approach on real images and found
that it can achieve high accuracy, objectivity, and robustness.
PMID- 25124289
TI - Acute renal failure as a form of presentation of sarcoidosis in a young adult: a
case report.
AB - INTRODUCTION: Sarcoidosis is a systemic granulomatous disease. Renal involvement
is a rare initial presentation of this disease. Few articles on renal involvement
as an initial presentation of sarcoidosis have been published in the literature.
CASE PRESENTATION: A 26-year-old Caucasian woman presented with acute renal
failure as an initial manifestation of sarcoidosis. CONCLUSIONS: Renal
involvement is an uncommon feature of sarcoidosis and it is essential to
establish a fast and correct diagnosis because early therapy avoids progression
to terminal renal failure.
PMID- 25124288
TI - Physiological and proteomic analyses of salt stress response in the halophyte
Halogeton glomeratus.
AB - Very little is known about the adaptation mechanism of Chenopodiaceae Halogeton
glomeratus, a succulent annual halophyte, under saline conditions. In this study,
we investigated the morphological and physiological adaptation mechanisms of
seedlings exposed to different concentrations of NaCl treatment for 21 d. Our
results revealed that H. glomeratus has a robust ability to tolerate salt; its
optimal growth occurs under approximately 100 mm NaCl conditions. Salt crystals
were deposited in water-storage tissue under saline conditions. We speculate that
osmotic adjustment may be the primary mechanism of salt tolerance in H.
glomeratus, which transports toxic ions such as sodium into specific salt-storage
cells and compartmentalizes them in large vacuoles to maintain the water content
of tissues and the succulence of the leaves. To investigate the molecular
response mechanisms to salt stress in H. glomeratus, we conducted a comparative
proteomic analysis of seedling leaves that had been exposed to 200 mm NaCl for 24
h, 72 h and 7 d. Forty-nine protein spots, exhibiting significant changes in
abundance after stress, were identified using matrix-assisted laser desorption
ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS/MS) and
similarity searches across EST database of H. glomeratus. These stress-responsive
proteins were categorized into nine functional groups, such as photosynthesis,
carbohydrate and energy metabolism, and stress and defence response.
PMID- 25124290
TI - The ability to suppress macrophage-mediated inflammation in orbital fat stem
cells is controlled by miR-671-5p.
AB - INTRODUCTION: Our previous works demonstrated that systemic orbital fat-derived
stem cell (OFSC) transplantation was effective in ameliorating lipopolysaccharide
(LPS)-induced extensive acute lung injury (ALI) in vivo mainly through paracrine
regulation of macrophage-mediated cytokine-storm. In this study, we explore the
molecular mechanism(s) of OFSCs regulating macrophage activity in a cytokine
inducible fashion. METHODS: LPS (100 ng/ml)-activated macrophages were treated by
conditioned medium from OFSCs (OFSCs-CM) or non-contact cultured with OFSCs for 6
hours. The potency of OFSCs on macrophage proliferation and pro-inflammation
ability were determined. Expression levels of pro-inflammatory cytokines in
macrophages, inducible immuno-modulatory factors in OFSCs, were investigated.
Deep sequencing analysis as well as interaction between microRNA (miRNA) and
genes of immuno-modulators in OFSCs induced by activated macrophages was
predicted by miRTar. Transfection of miRNA inhibitor into OFSCs was performed.
Real-time RT-PCR and transplantation of OFSCs into mice with LPS-induced ALI
confirmed the in vitro and in vivo mechanism. RESULTS: The paracrine effect of
OFSCs on inhibition of macrophage pro-inflammatory cytokine release was more
potent than induction of macrophage G0/G1 cell cycle arrest. OFSCs-CM suppressed
LPS-induced inducible nitric oxide synthetase and the pro-inflammatory cytokines
such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 alpha, and IL
1 beta expression in macrophages. Under non-contact culture, LPS-activated
macrophages effectively triggered the expression of soluble immuno-modulating
factors in OFSCs, i.e., IL-10, IL-1 receptor antagonist (IL-1 RA), indoleamine
2,3-dioxygenase, and soluble TNF receptor type II (sTNF RII). Under miRTar
prediction, miR-671-5p was identified as a critical microRNA in regulation of
multiple immune-modulating factors in OFSCs response to macrophages. The baseline
level of miR-671-5p was high in OFSCs, and down-regulation of miR-671-5p upon co
culture with activated macrophages was observed. MiR-671-5p inhibitor
transfection into OFSCs selectively enhanced the IL-1 RA and sTNF RII
expressions. In addition, inhibition of miR-671-5p in OFSCs enhanced the anti
inflammatory ability against LPS-induced ALI. CONCLUSION: The paracrine effect of
OFSCs inhibits the pro-inflammatory ability and proliferation of macrophages. The
immune-modulation capacity of OFSCs can be triggered by activated macrophages,
and down-regulation of miR-671-5p enhances OFSC immuno-modulation ability by up
regulating IL-1 RA and sTNF RII expression.
PMID- 25124291
TI - Switching to emtricitabine, tenofovir and rilpivirine as single tablet regimen in
virologically suppressed HIV-1-infected patients: a cohort study.
AB - OBJECTIVES: Emtricitabine/tenofovir/rilpivirine as a single-tablet regimen (STR)
is widely used without licence in treatment-experienced patients. The purpose of
this retrospective observational study was to assess viral suppression of ART
experienced patients switching to STR. METHODS: We assessed 131 pretreated
patients switching to STR with HIV RNA <400 HIV-1 RNA copies/mL. The primary
outcome measure was the proportion of patients at week 24 with HIV RNA <40
copies/mL. RESULTS: By week 24, eight patients had stopped STR: four because of
adverse events and four for other reasons. Three virological failures were
observed; among these, at least one patient developed cross-resistance to
nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse
transcriptase inhibitors (NNRTIs), in particular with the E138K pattern. In
intent-to-treat analysis, 92% of participants (120 of 131) achieved HIV RNA <40
copies/mL. Only grade 1 to 2 adverse events were observed, mainly consisting of
increased liver enzymes (n=33). Systemic exposure to rilpivirine was above the
usually observed steady-state levels for the 18 measurements assessed.
CONCLUSIONS: Efficacy and tolerability are similar to those in treatment-naive
patients.
PMID- 25124293
TI - Psychological factors predicting outcome after traumatic injury: the role of
resilience.
AB - BACKGROUND: Increasingly, studies have examined the psychological impact on
individuals who survive a traumatic physical injury. The primary aim of this
study was to determine the stability of resilience and its association with
depressive symptoms. METHODS: This study included 110 adults admitted to a Level
I trauma center. Resilience and depression were measured at baseline and 12
months. Injury-related variables included Glasgow Coma Scale, Injury Severity
Score, etiology of injury, and type of injury. RESULTS: Analysis revealed that
resilience remained stable over 12 months regardless of injury severity,
etiology, or type. Negative correlations were found between baseline resilience
and 12-month depression (P < .01), as well as Glasgow Coma Scale and depression
(P = .001). CONCLUSIONS: Injured individuals with low resilience are more likely
to be depressed at 12 months. Assessing resilience at the time of injury may be
useful in identifying those at risk for depression 1 year later.
PMID- 25124294
TI - Perihilar cholangiocarcinoma: paradigms of surgical management.
AB - Cholangiocarcinoma is a lethal disease with increasing incidence worldwide.
Perihilar cholangiocarcinoma represents the most common type of
cholangiocarcinoma. Despite major development on surgical strategies over the
past 20 years, the 5-year survival rate after surgery has remained below 40%,
often in the vicinity of 20%. Most perihilar cholangiocarcinomas, however, are
unresectable at the time of the diagnosis. The recent use of aggressive
approaches based on better image modality, specific perioperative management, and
a multidisciplinary approach have enabled to convert the use of palliative
therapies to more radical surgery. This review focuses on the recent advances in
surgical treatment for perihilar cholangiocarcinoma including liver
transplantation with their respective impact on patient survival.
PMID- 25124292
TI - Does intramesorectal excision for ulcerative colitis impact bowel and sexual
function when compared with total mesorectal excision?
AB - BACKGROUND: Proctectomy for ulcerative colitis (UC) can be performed via
intramesorectal (IME) or total mesorectal excision (TME). METHODS: We compared
patient-reported bowel and sexual function among IME versus TME UC patients
(September 2000 to March 2011) using the Memorial Sloan-Kettering Cancer Center
Bowel Function scale, Fecal Incontinence Quality of Life, Fecal Incontinence
Severity Index, Female Sexual Function Instrument, and International Index of
Erectile Dysfunction surveys. RESULTS: Eighty-nine IME versus TME patients (35 +/
2 years, 57% male, 62% IME) had similar baseline characteristics, although IME
patients had more open procedures (P <= .03). IME patients reported better fecal
continence (P = .009) but similar fecal incontinence-related quality of life (P
>= .44). For sexual function, there were no differences for either women (Female
Sexual Function Instrument; P >= .20) or men (International Index of Erectile
Dysfunction; P >= .22). CONCLUSIONS: IME appears to be associated with better
fecal continence but no difference in overall bowel or sexual function compared
with TME in patients with UC.
PMID- 25124296
TI - Triple opportunistic pulmonary cavitary disease after cord blood transplantation.
AB - Opportunistic infectious diseases in patients are variable and depend on the host
as well as the type of immunosuppression. Cord blood transplant recipients appear
to be particularly vulnerable to infectious complications. Sequential or
concurrent opportunistic infectious diseases can be particularly difficult to
manage and have increased mortality. We present a young patient, status post cord
blood transplantation for acute myelogenous leukemia, who developed a large
pulmonary mass-like infection with Aspergillus, cytomegalovirus, and
Mycobacterium avium complex. Radiological, surgical, and pathological features
are described.
PMID- 25124295
TI - The effect of antecolic versus retrocolic reconstruction on delayed gastric
emptying after classic non-pylorus-preserving pancreaticoduodenectomy.
AB - BACKGROUND: Delayed gastric emptying (DGE) after pancreaticoduodenectomy
increases length of hospital stay and costs, and may be influenced by surgical
techniques. METHODS: We retrospectively compared 400 patients with antecolic
gastrojejunostomy with 400 patients with retrocolic gastrojejunostomy for the
occurrence of DGE. RESULTS: The prevalence of DGE was 15% in the antecolic group
and 21% in the retrocolic group (P = .021), and median length of stay was shorter
for the former (8 vs. 10 days, P = .001). The difference was statistically
significant with grade A DGE (9% vs. 14%, P = .038), but not B or C. In a
multivariate analysis, DGE was influenced by retrocolic reconstruction, as well
as older age, chronic pancreatitis, preoperative bilirubin level, a history of
previous upper abdominal surgery, and postoperative pancreatic fistula.
CONCLUSIONS: An antecolic gastrojejunostomy for classic non-pylorus-preserving
pancreaticoduodenectomy is associated with a lower incidence of mild DGE (grade
A) and a shorter length of stay.
PMID- 25124297
TI - Review: Bone conduction devices and contralateral routing of sound systems in
single-sided deafness.
AB - OBJECTIVES/HYPOTHESIS: Systematically review the literature on the clinical
outcome of bone conduction devices (BCD) and contralateral routing of sound
systems (CROSS) for patients with single-sided deafness (SSD). DATA SOURCES:
PubMed, Embase, Cochrane Library, and CINAHL databases were searched up to April
7, 2014. REVIEW METHODS: All studies investigating BCD and CROSS for patients
with SSD on speech perception in noise, sound localization, or quality of life
were selected and critically appraised. RESULTS: In total, 46 articles were
retrieved, of which six satisfied the eligibility criteria. Critical appraisal
showed that five studies (n = 91) carried a moderate to high directness of
evidence and a low to moderate risk of bias. Subsequently, study characteristics
and outcome measurements were extracted. Due to large heterogeneity between
studies, pooling of data was not feasible. Studies did not show a clear advantage
of BCD or CROSS on speech perception in noise. BCD and CROSS lead to the same
sound localization ability as the unaided condition. Quality of life did not
differ significantly between conditions; however, subjective speech communication
did improve. CONCLUSION: No high level of evidence studies compare BCD and CROSS
in patients with SSD. Literature showed no beneficial effect of BCD or CROSS
regarding speech perception in noise and sound localization. Subjective speech
communication demonstrated a moderate improvement with BCD and CROSS. High
evidence studies comparing all treatment options for single-sided deafness should
be conducted.
PMID- 25124298
TI - An evaluation of interactive computer training to teach instructors to implement
discrete trials with children with autism.
AB - Discrete-trial instruction (DTI) is a teaching strategy that is often
incorporated into early intensive behavioral interventions for children with
autism. Researchers have investigated time- and cost-effective methods to train
staff to implement DTI, including self-instruction manuals, video modeling, and
interactive computer training (ICT). ICT combines the best components of self
instruction manuals and video models, and have the same benefits; however, there
is limited research on this training method. Therefore, the purpose of this study
was to investigate ICT to teach university students to implement DTI with
children with autism. All participants' teaching fidelity increased during both
role-plays with an adult and instructional sessions with a child with autism. In
addition, participants demonstrated an increase in teaching fidelity with
untrained instructional programs. All participants were able to complete training
in an average of 2 hr, and social validity ratings were high.
PMID- 25124299
TI - Diaphragmatic hernia after liver transplantation in children: case series and
review of the literature.
AB - A diaphragmatic hernia (DH) is a rare complication of pediatric liver
transplantation (LT), with multiple factors implicated in the pathophysiology. It
is a potentially life-threatening condition in the absence of early recognition
and surgical treatment. A DH after LT has been reported in 16 patients in 7 case
series. We report 10 cases from our institution and review the published
literature to understand the underlying pathophysiology. The study sample
included all children (<18 years of age) who underwent LT from October 1989 to
August 2013 at our center and subsequently presented with a DH. Among 4433 LT
procedures performed in this time period, 1032 were for children. Ten DH cases
were recognized, and risk factors were assessed. The mean age at diagnosis was
4.9 years, all patients with a DH received left lateral segment split grafts, and
the mean graft weight was 248 +/- 41 g with a mean graft-to-recipient body weight
ratio (GBWR) of 3% +/- 1.22% (range = 1.7%-5.0%). The mean cold ischemia time was
510.7 +/- 307.6 minutes (range = 60-900 minutes). Six patients had a primary
abdominal muscle closure, 3 had a temporary Silastic mesh closure, and 1 had a
skin closure only. Postoperative ascites and pleural effusion did not appear to
be significant risk factors. All 10 children presented with a right
posterolateral DH, with 1 also having a left DH. The small bowel was herniated in
the majority. All patients underwent prompt surgical intervention without
complications. An early age, a split graft, and a high GBWR may be risk factors
for a DH. A high index of suspicion and prompt surgical intervention minimize
complications.
PMID- 25124300
TI - Vertically-aligned BCN nanotube arrays with superior performance in
electrochemical capacitors.
AB - Electrochemical capacitors (EC) have received tremendous interest due to their
high potential to satisfy the urgent demand in many advanced applications. The
development of new electrode materials is considered to be the most promising
approach to enhance the EC performance substantially. Herein, we present a high
capacity capacitor material based on vertically-aligned BC2N nanotube arrays (VA
BC2NNTAs) synthesized by low temperature solvothermal route. The obtained VA
BC2NNTAs display the good aligned nonbuckled tubular structure, which could
indeed advantageously enhance capacitor performance. VA-BC2NNTAs exhibit an
extremely high specific capacitance, 547 Fg(-1), which is about 2-6 times larger
than that of the presently available carbon-based materials. Meanwhile, VA
BC2NNTAs maintain an excellent rate capability and high durability. All these
characteristics endow VA-BC2NNTAs an alternative promising candidate for an
efficient electrode material for electrochemical capacitors (EC).
PMID- 25124301
TI - Conjugate umpolung of beta,beta-disubstituted enals by dual catalysis with an N
heterocyclic carbene and a Bronsted acid: facile construction of contiguous
quaternary stereocenters.
AB - A sterically hindered homoenolate has been generated by the NHC-catalyzed
conjugate umpolung of beta,beta-disubstituted enals and successfully employed in
a facile stereoselective annulation with isatins. The strategy provides efficient
access to spirocyclic oxindoles bearing two highly congested contiguous
quaternary carbon centers. The use of a Bronsted acid cocatalyst was found to be
crucial for guaranteeing both excellent reactivity and high stereoselectivity.
PMID- 25124302
TI - The effect of environment on nursing and health promotion for women.
PMID- 25124306
TI - Nasal reconstruction: a dermatological surgeon's approach to recreating the
'aesthetic king' of the central face.
PMID- 25124303
TI - Correlates of polysomnographic sleep changes in cocaine dependence: self
administration and clinical outcomes.
AB - BACKGROUND: Abstinence from chronic cocaine use is associated with abnormal sleep
architecture. As sleep abnormalities are associated with clinical outcome in
alcohol dependence, we hypothesized a similar relationship in cocaine dependence.
METHODS: We report data from a cocaine self-administration study (N=12) and the
placebo arm of a randomized clinical trial (N=20). Self-administration
participants underwent three cocaine self-administration sessions during a three
week inpatient stay. Treatment participants underwent two weeks of inpatient
followed by six weeks of outpatient treatment including once-weekly cognitive
behavioral therapy. Measurements included polysomnography from early and late in
abstinence during the inpatient stays. Clinical outcomes included amount of
cocaine self-administered, urine tests, and self-reported use and withdrawal
symptoms. RESULTS: Change in slow-wave sleep from early to late abstinence
(DeltaSWS; p=0.05), late abstinence rapid eye movement sleep (REM; p=0.002), and
late abstinence total sleep time (p=0.02) were negatively correlated with the
amount of cocaine self-administered. Early abstinence REM was positively
correlated with withdrawal symptoms (p=0.02). Late abstinence REM was positively
correlated with percent negative urines and maximum consecutive number of days
abstinent (both p<0.001). DeltaSWS was positively correlated with percent
negative urines (p=0.03) and participants with increased SWS had greater percent
negative urines (p=0.008) and maximum consecutive number of days abstinent
(p=0.009). CONCLUSIONS: Correlations between sleep deficits and amount of cocaine
self-administered, clinical outcomes, and severity of withdrawal symptoms
underscore the relevance of sleep in clinical outcomes in the treatment of
cocaine dependence.
PMID- 25124304
TI - Smoking, MATRICS consensus cognitive battery and P50 sensory gating in a Han
Chinese population.
AB - BACKGROUND: The effects of smoking on cognitive performance have long been
studied, with mixed results. P50 sensory gating has been used as endophenotype
for studying nicotinic systems genetics, and P50 gating deficits have been
reported to be a sensitive biomarker for cognitive impairment in schizophrenia.
This study examined the inter-relationship between P50 suppression, cognitive
function, and smoking in a healthy Han Chinese population, which has not been
reported before. METHODS: We recruited 82 healthy male subjects, including 48
smokers and 34 non-smokers who were matched for age and education. The authors
measured P50 sensory gating and administered the Chinese-language version of the
MATRICS consensus cognitive battery (MCCB) and Stroop tests. RESULTS: The results
showed that the smokers scored lower than nonsmokers on the MCCB brief
visuospatial memory test (BVMT) index and the STROOP test. Furthermore, the MCCB
total score was negatively associated with number of cigarettes smoked per day in
the smoker group. However, P50 sensory gating was not associated with either
smoking status or any cognitive performance. CONCLUSIONS: Our results show that
smoking is associated with cognitive impairment, but not with P50 sensory gating.
PMID- 25124308
TI - Reconstructing the nasal dorsum.
AB - The skin of the nasal dorsum and bridge is more forgiving in terms of
reconstructive options. Individual differences in skin laxity, nasal length and
sebaceous composition impact on reconstructive choice as do the size, depth and
exact location of the surgical defect. For many, if not all, defects in this area
there are multiple different reconstructive options available all of which can
result in equivalent and excellent results. Oftentimes there is no clear
advantage of one repair over another and the choice becomes one of personal
preference based on experience. No proscriptive approach or algorithm can be
usefully applied in this setting. Key considerations include the location of the
defect (distal vs. proximal nasal dorsum), the position of the defect (midline or
off-centre) and the texture of the skin involved (sebaceous vs. non-sebaceous).
Defects may be considered complex if they border on, or cross onto adjacent
cosmetic units. Examples include defects extending onto the nasal tip, tip-ala
junction, sidewall, nasal root-glabella and medial canthus. The adjacent
reservoirs of tissue redundancy that can be utilized in flap reconstruction
include the nasal sidewall, the nasal dorsum itself, the glabella, the
midline/paramedian forehead and the medial cheek. Nearly all flaps on the nasal
dorsum require subnasalis muscle dissection to effect sufficient movement and to
ensure adequate flap vascularity and viability. The nasal bridge and glabella
have much thicker skin and it is usually sufficient to dissect in the
subcutaneous plane rather than disrupting the deeper procerus and corrugator
muscles. Thick sebaceous skin is generally stiffer, moves less easily and
closures may result in greater wound tension. These factors together with a
tendency for sutures to tear through easily potentially increases the risk of
complications. Greater consideration should be given to the exact type of flap or
graft chosen in these patients.
PMID- 25124305
TI - Separate and combined effects of the GABAA positive allosteric modulator diazepam
and Delta9-THC in humans discriminating Delta9-THC.
AB - BACKGROUND: Our previous research suggested the involvement of gamma-aminobutyric
acid (GABA), in particular the GABAB receptor subtype, in the interoceptive
effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC). The aim of the present
study was to determine the potential involvement of the GABAA receptor subtype by
assessing the separate and combined effects of the GABAA positive allosteric
modulator diazepam and Delta(9)-THC using pharmacologically selective drug
discrimination procedures. METHODS: Ten cannabis users learned to discriminate 30
mg oral Delta(9)-THC from placebo and then received diazepam (5 and 10mg),
Delta(9)-THC (5, 15 and 30 mg) and placebo, alone and in combination. Self
report, task performance and physiological measures were also collected. RESULTS:
Delta(9)-THC functioned as a discriminative stimulus, produced subjective effects
typically associated with cannabinoids (e.g., High, Stoned, Like Drug) and
elevated heart rate. Diazepam alone impaired performance on psychomotor
performance tasks and increased ratings on a limited number of self-report
questionnaire items (e.g., Any Effect, Sedated), but did not substitute for the
Delta(9)-THC discriminative stimulus or alter the Delta(9)-THC discrimination
dose-response function. Similarly, diazepam had limited impact on the other
behavioral effects of Delta(9)-THC. CONCLUSIONS: These results suggest that the
GABAA receptor subtype has minimal involvement in the interoceptive effects of
Delta(9)-THC, and by extension cannabis, in humans.
PMID- 25124307
TI - Nasal anatomy for the dermatological surgeon.
AB - The nose is an important site of skin pathology and skin cancer in particular,
underlining the importance of the nose to the practice of dermatology. This
article is intended to serve as an overview of the anatomy of the nose for
dermatologists and dermatological surgeons. Areas of clinical relevance are
emphasized with examples.
PMID- 25124310
TI - Reconstructing the nasal tip.
AB - Given the intricate contours of adjacent concavities and convexities, the limited
area from which to recruit similar skin, and variable areas of skin thickness,
elasticity and adnexal density, reconstruction of the nasal tip is a challenging
process. When approaching nasal reconstruction we have often found it helpful to
partition defects into two subgroups: those that fall within the upper two-thirds
of the nose and those that fall within the lower third. Within this framework of
the lower third, we present our reconstructive approach to surgical defects of
the nasal tip.
PMID- 25124309
TI - Repair of the nasal sidewall.
AB - Repair of the nasal sidewall after skin cancer excision is generally best
approached with the use of local flaps for aesthetic reasons. The sidewall may be
divided into upper and lower sections and defects described as small, medium or
large. In this section I will review the flaps that I feel make best use of
adjacent tissue reservoirs allowing aesthetic placement of incisions while
protecting free margins and function, and that reward the operator with reliably
superior results for the patient.
PMID- 25124311
TI - The reconstruction of the nasal ala with interpolated flaps from the cheek and
forehead: design and execution modifications to improve surgical outcomes.
AB - The nasal ala, critically important in the function and appearance of the central
face, has significant reconstructive demands given the lack of suitable adjacent
donor tissue that can be used to repair all but the smallest surgical defects in
this area. Interpolated flaps from the forehead and cheek have long been ideal
reconstructive alternatives for the repair of larger or more difficult alar
wounds, and with the design and execution modifications described here, the
dermatological surgeon can offer more appropriate restoration of this critically
important aesthetic unit.
PMID- 25124312
TI - Multiresidue determination of UV filters in water samples by solid-phase
extraction and liquid chromatography with tandem mass spectrometry analysis.
AB - UV filters, contained in sunscreens and other cosmetic products, as well as in
some plastics and industrial products, are nowadays considered contaminants of
emerging concern because their widespread and increasing use has lead to their
presence in the environment. Furthermore, some UV filters are suspected to have
endocrine disruption activity. In the present work, we developed an analytical
method based on liquid chromatography with tandem mass spectrometry for the
determination of UV filters in tap and lake waters. Sixteen UV filters were
extracted from water samples by solid-phase extraction employing graphitized
carbon black as adsorbent material. Handling 200 mL of water sample, satisfactory
recoveries were obtained for almost all the analytes. The limits of detection and
quantification of the method were comparable to those reported in other works,
and ranged between 0.7-3.5 and 1.9-11.8 ng/L, respectively; however in our case
the number of investigated compounds was larger. The major encountered problem in
method development was to identify the background contamination sources and
reduce their contribution. UV filters were not detected in tap water samples,
whereas the analyses conducted on samples collected from three different lakes
showed that the swimming areas are most subject to UV filter contamination.
PMID- 25124313
TI - Primary myelofibrosis: 2014 update on diagnosis, risk-stratification, and
management.
AB - DISEASE OVERVIEW: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm
characterized by stem cell-derived clonal myeloproliferation, abnormal cytokine
expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary
hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and
shortened survival. DIAGNOSIS: DIAGNOSIS is based on bone marrow morphology. The
presence of JAK2, CALR, or MPL mutation is supportive but not essential for
diagnosis; approximately 90% of patients carry one of these mutations and 10% are
"triple-negative." None of these mutations are specific to PMF and are also seen
in essential thrombocythemia (ET). Prefibrotic PMF mimics ET in its presentation
and the distinction, enabled by careful bone marrow morphological examination, is
prognostically relevant. Differential diagnosis also includes chronic myeloid
leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute
myeloid leukemia. RISK STRATIFICATION: The Dynamic International Prognostic
Scoring System-plus (DIPSS-plus) uses eight predictors of inferior survival: age
>65 years, hemoglobin <10 g/dL, leukocytes >25 * 10(9) /L, circulating blasts
>=1%, constitutional symptoms, red cell transfusion dependency, platelet count
<100 * 10(9) /L, and unfavorable karyotype (i.e., complex karyotype or sole or
two abnormalities that include +8, -7/7q-, i(17q), inv(3), -5/5q-, 12p-, or 11q23
rearrangement). The presence of 0, 1, "2 or 3," and >=4 adverse factors defines
low, intermediate-1, intermediate-2, and high-risk disease with median survivals
of approximately 15.4, 6.5, 2.9, and 1.3 years, respectively. High risk disease
is also defined by CALR(-) /ASXL1(+) mutational status. RISK-ADAPTED THERAPY:
Observation alone is adequate for asymptomatic low/intermediate-1 risk disease,
especially with CALR(+) /ASXL1(-) mutational status. Stem cell transplant is
considered for DIPSS-plus high risk disease or any risk disease with CALR(-)
/ASXL1(+) mutational status. Investigational drug therapy is reasonable for
symptomatic intermediate-1 or intermediate-2 risk disease. Splenectomy is
considered for drug-refractory splenomegaly. Involved field radiotherapy is most
useful for post-splenectomy hepatomegaly, non-hepatosplenic EMH, PMF-associated
pulmonary hypertension, and extremity bone pain.
PMID- 25124314
TI - Response to the Letter-to-the-Editor Regarding "The Two Year Cost Effectiveness
of Three Options to Treat Lumbar Spinal Stenosis Patients".
PMID- 25124316
TI - Geometric accuracy in three-dimensional coordinates of Leksell stereotactic skull
frame with wide-bore 1.5-T MRI compared with conventional 1.5-T MRI.
AB - The use of 1.5-tesla (T) magnetic resonance (MR) imaging with a wide and
simultaneously short bore enhances patient comfort compared with traditional 1.5
T MR imaging and is becoming increasingly available in stereotactic radiosurgery
treatment planning. However, the geometric accuracy seems unavoidably worse in
wide-bore MR imaging than in conventional MR imaging. We assessed the geometric
distortion of the stereotactic image attached on a Leksell skull frame in
conventional and wide-bore 1.5-T MR imaging. Two kinds of acrylic phantoms were
placed on the skull frame and were scanned using computed tomography (CT) and
conventional and wide-bore 1.5-T MR imaging. The three-dimensional coordinates on
both MR imaging were compared with those on CT. Deviations of measured
coordinates at selected points (x = 50, 100, 150 mm; y = 50, 100, 150 mm) were
indicated on different axial planes (z = 50, 75, 100, 125, 150 mm). The
differences of coordinates were less than 1.0 mm in the entire treatable area for
conventional MR imaging. With the large bore system, the differences of the
coordinates were less than 1.0 mm around the center but substantially exceeded
1.0 mm in the peripheral regions. Further study is needed to increase the
geometric accuracy of wide-bore MR imaging for stereotactic radiosurgery
treatment planning.
PMID- 25124315
TI - A single exposure to cocaine during development elicits regionally-selective
changes in basal basic Fibroblast Growth Factor (FGF-2) gene expression and
alters the trophic response to a second injection.
AB - RATIONALE: During adolescence, the brain is maturing and more sensitive to drugs
of abuse that can influence its developmental trajectory. Recently, attention has
been focused on basic fibroblast growth factor (FGF-2) given that its
administration early in life enhances the acquisition of cocaine self
administration and sensitization at adulthood (Turner et al. (Pharmacol Biochem
Behav 92:100-4, 2009), Clinton et al. (Pharmacol Biochem Behav103:6-17, 2012)).
Additionally, we found that abstinence from adolescent cocaine exposure long
lastingly dysregulates FGF-2 transcription (Giannotti et al. (Psychopharmacology
(Berl) 225:553-60, 2013 ). OBJECTIVES: The objectives of the study are to
evaluate if (1) a single injection of cocaine (20 mg/kg) at postnatal day 35
alters FGF-2 messenger RNA (mRNA) levels and (2) the first injection influences
the trophic response to a second injection (10 mg/kg) provided 24 h or 7 days
later. RESULTS: We found regional differences in the FGF-2 expression pattern as
either the first or the second injection of cocaine by themselves upregulated FGF
2 mRNA in the medial prefrontal cortex and nucleus accumbens while downregulating
it in the hippocampus. The first injection influences the trophic response of the
second. Of note, 24 h after the first injection, accumbal and hippocampal FGF-2
changes produced by cocaine in saline-pretreated rats were prevented in cocaine
pretreated rats. Conversely, in the medial prefrontal cortex and hippocampus 7
days after the first injection, the cocaine-induced FGF-2 changes were modified
by the subsequent exposure to the psychostimulant. CONCLUSIONS: These findings
show that a single cocaine injection is sufficient to produce enduring changes in
the adolescent brain and indicate that early cocaine priming alters the
mechanisms regulating the trophic response in a brain region-specific fashion.
PMID- 25124317
TI - A detailed view on sulphur metabolism at the cellular and whole-plant level
illustrates challenges in metabolite flux analyses.
AB - Understanding the dynamics of physiological process in the systems biology era
requires approaches at the genome, transcriptome, proteome, and metabolome
levels. In this context, metabolite flux experiments have been used in mapping
metabolite pathways and analysing metabolic control. In the present review,
sulphur metabolism was taken to illustrate current challenges of metabolic flux
analyses. At the cellular level, restrictions in metabolite flux analyses
originate from incomplete knowledge of the compartmentation network of metabolic
pathways. Transport of metabolites through membranes is usually not considered in
flux experiments but may be involved in controlling the whole pathway. Hence,
steady-state and snapshot readings need to be expanded to time-course studies in
combination with compartment-specific metabolite analyses. Because of species
specific differences, differences between tissues, and stress-related responses,
the quantitative significance of different sulphur sinks has to be elucidated;
this requires the development of methods for whole-sulphur metabolome approaches.
Different cell types can contribute to metabolite fluxes to different extents at
the tissue and organ level. Cell type-specific analyses are needed to
characterize these contributions. Based on such approaches, metabolite flux
analyses can be expanded to the whole-plant level by considering long-distance
transport and, thus, the interaction of roots and the shoot in metabolite fluxes.
However, whole-plant studies need detailed empirical and mathematical modelling
that have to be validated by experimental analyses.
PMID- 25124318
TI - Roles of melatonin in abiotic stress resistance in plants.
AB - In recent years melatonin has emerged as a research highlight in plant studies.
Melatonin has different functions in many aspects of plant growth and
development. The most frequently mentioned functions of melatonin are related to
abiotic stresses such as drought, radiation, extreme temperature, and chemical
stresses. This review mainly focuses on the regulatory effects of melatonin when
plants face harsh environmental conditions. Evidence indicates that environmental
stress can increase the level of endogenous melatonin in plants. Overexpression
of the melatonin biosynthetic genes elevates melatonin levels in transgenic
plants. The transgenic plants show enhanced tolerance to abiotic stresses.
Exogenously applied melatonin can also improve the ability of plants to tolerate
abiotic stresses. The mechanisms by which melatonin alleviates abiotic stresses
are discussed.
PMID- 25124319
TI - Elevated levels of cyclooxygenase 1 and 2 in human cyclosporine induced gingival
overgrowth.
AB - OBJECTIVE: This study was carried out to immuno-localize and estimate the levels
of cyclooxygenase 1 and 2 in human gingival tissue samples from healthy
individuals, chronic periodontitis patients and patients with cyclosporine
induced gingival overgrowth. METHODS: Group I consisted of individuals with
healthy gingiva (n=6), Group II - cyclosporine induced gingival overgrowth (n=9)
and Group III - chronic periodontitis patients (n=6). Gingival tissue samples
were collected from subjects of all the three groups. COX-1, COX-2 levels were
estimated in tissue homogenates by enzyme activity assay. Immuno-localization for
COX-1 and COX-2 was also done in sections of gingival tissue. RESULTS: The study
results demonstrated a significantly higher mean levels of COX-1 and 2 in drug
induced gingival overgrowth samples (p<0.05). COX-1 and COX-2 was localized to
epithelium and connective tissue in human gingival tissue sections from
cyclosporine induced gingival overgrowth. CONCLUSION: Cyclooxygenase enzymes
appear to be potential mediators involved in the pathogenesis of cyclosporine
induced gingival overgrowth.
PMID- 25124320
TI - Dynamic contrast enhanced MR imaging for rectal cancer response assessment after
neo-adjuvant chemoradiation.
AB - BACKGROUND: Patient selection for organ sparing treatment after good response to
neo-adjuvant chemoradiation (CRT) for locally advanced rectal cancer is
challenging as no optimal restaging modality is available after CRT. In this
study, we assessed the value of dynamic contrast enhanced magnetic resonance
imaging (DCE-MRI) for rectal cancer pathological response prediction. METHODS: In
51 patients with locally advanced rectal cancer, the tumor volume and volume
transfer constant (Ktrans) were obtained at 3 Tesla before CRT and surgery. The
predictive potential for pathological complete response (pCR) and good response
(GR) was assessed. GR was defined as pCR and near-pCR based on the tumor
regression grade. RESULTS: The GR group consisted of 10 patients (19.6%) with six
pCR (11.8%). Both the post-CRT tumor volume and post-CRT Ktrans values and the
relative change in volume (DeltaVolume) and Ktrans (DeltaKtrans) were predictive
for pathological response. DeltaKtrans showed the best predictive potential with
a positive predictive value (PPV) of 100% for GR using a cutoff value of 32%
reduction in Ktrans. For pCR the best PPV was 80% with a multiparameter model
containing DeltaVolume and DeltaKtrans. CONCLUSION: DCE-MRI has predictive
potential for pathological response after CRT in rectal cancer with the relative
DeltaKtrans being the most predictive parameter.
PMID- 25124321
TI - Peeking into a cool future: genome editing to delete PCSK9 and control
hypercholesterolemia in a single shot.
PMID- 25124324
TI - Deepak Srivastava: follows his heart to study the heart.
PMID- 25124323
TI - Study of exonic variation identifies incremental information regarding lipid
related and coronary heart disease genes.
PMID- 25124325
TI - Correction.
PMID- 25124322
TI - Ceramide signaling in the coronary microcirculation: a double-edged sword?
PMID- 25124326
TI - A novel variant in GABRB2 associated with intellectual disability and epilepsy.
AB - The gamma-aminobutyric acid type A (GABAA ) receptor is one of the three main
classes of receptors activated by GABA, the principal inhibitory neurotransmitter
in the central nervous system. Mutations in genes encoding various subunits of
this receptor (GABRA1, GABRA2, GABRA4, GABRA5, GABRA6, GABRB1, GABRB3, GABRG1,
GABRG2, GABRG3, and GABRD) are implicated in a number of neurological and
developmental disorders, including epilepsy and autism. To date, no human
genetics studies have implicated mutations in GABRB2, encoding the beta2 subunit
of the GABAA receptor, with neurodevelopmental disorders. Here we present a 12
year-old girl with intellectual disability and epilepsy, who was discovered by
whole exome sequencing to have a de novo heterozygous missense variant in exon 4
of GABRB2 (c.236T>C; p.M79T). This variant is likely pathogenic, based on in
silico analyses, as well as the fact that it results in the non-conservative
substitution of a non-polar amino acid with a polar amino acid at a position that
is evolutionarily conserved across multiple species. Our findings underscore the
need for further investigation into the mechanisms by which mutations in GABRB2
contribute to neurological and developmental dysfunction.
PMID- 25124327
TI - CDC Kerala 3: At-risk baby clinic service using different screening tools-
outcome at 12 months using Developmental Assessment Scale for Indian Infants.
AB - OBJECTIVES: To describe CDC Kerala experience of establishing an at-risk baby
clinic and the comparison of different developmental screening tools at 12 mo
against the gold standard Developmental Assessment Scale for Indian Infants
(DASII). METHODS: At risk baby clinic of CDC, Kerala was established as a
facility for follow up of NICU graduates from Sree Avittam Thirunal Hospital at
2, 4, 6, 8 and 12 mo corrected age and during each visit the mother is taught the
CDC model early stimulation by developmental therapists and encouraged to
continue to do the same at home. At 12 mo, assessment results of four simple
developmental tools were compared with the gold standard DASII administered by a
senior developmental therapist. RESULTS: Out of a total of 800 babies, outcome
measurements at 12 mo were available for 604 infants. The prevalence of
developmental delay using the screening tools, CDC grading for standing, Amiel
Tison angles and DDST II (Denver II) gross motor were 24.8, 24 and 24.3%
respectively and using DASII, a diagnostic tool (13.3%). Also the combination of
Amiel Tison angles, CDC standing grading and DDST gross motor against DASII motor
DQ had high specificity (94.15%) and negative predictive value (NPV) (70.18%) but
with a very low sensitivity of 14.58% and low positive predictive value (PPV) of
53.85%. It was observed that a significant odds ratio for DASII mental deviation
quotient (DQ) was seen for neonatal seizures (2.34) and low birth weight (1.49).
CONCLUSION: The prevalence of developmental delay using the screening tools, CDC
grading for standing, Amiel Tison angles and DDST II (Denver II) gross motor were
24.8, 24 and 24.3% respectively and together they had a high specificity, NPV and
accuracy against DASII motor DQ as gold standard at one year assessment.
PMID- 25124328
TI - CDC Kerala 5: Developmental therapy clinic experience--use of Child Development
Centre grading for motor milestones.
AB - OBJECTIVES: To document the experiences of the intervention given to children who
attended the developmental therapy clinic of Child Development Centre (CDC)
Kerala, a specialized clinic for providing developmental intervention/therapy for
babies less than two years with developmental delay/disability. METHODS: All the
babies referred to this speciality clinic from developmental screening/evaluation
clinics of CDC were registered in the clinic and re-evaluation was done using CDC
grading for head holding, sitting, standing, Amiel Tison passive angles, and
Trivandrum Developmental Screening Chart (TDSC) 0-2 y. RESULTS: Out of a total of
600 consecutive babies below 2 y with developmental delay/disability referred to
developmental therapy clinic, on comparing the test results at enrollment and
after 6 mo of intervention, a statistically significant reduction was observed
(i) in the 2-4 mo age group with regard to abnormal TDSC (25.5%), (ii) in the 4-8
mo age group with regard to abnormal head holding grade (87.1%) and abnormal TDSC
(19.4%), (iii) in the 8-12 mo age group, with regard to abnormal sitting grade
(71.7%) and (iv) in the above 12 mo age group with regard to abnormal sitting
grade (35.3%) and abnormal standing grade (78.8%). CONCLUSIONS: The experience of
organizing the developmental intervention/therapy clinic at CDC Kerala has shown
that therapy services by developmental therapists in a centre and supportive
therapy by mother at home is useful in improving the developmental status of
children with developmental delay.
PMID- 25124329
TI - Recent advances in neonatal seizures.
AB - Neonatal seizures are the most important indicators of underlying brain injury.
Seizures in a neonate are different from seizures in older children in many
aspects including clinical presentation and etiology. The neonatal brain is
immature and tends to have a decreased seizure threshold. Neonatal seizures are
classified, based on their presentation as, clinical seizures, electroclinical
seizures and electroencephalographic seizures; based on the pathophysiology as
epileptic and nonepileptic seizures; and also on the basis of the etiology.
Hypoxic ischemic encephalopathy is the leading cause of neonatal seizures,
followed by intracranial hemorrhage, metabolic causes such as hypoglycemia and
hypocalcemia, intracranial infections and strokes. Neonatal epilepsy syndromes
are rare. Electroencephalography (EEG) is the gold standard for diagnosis.
Amplitude integrated EEG (aEEG) is also used for continuous monitoring. The
approach to management consists of initial stabilization of the neonate followed
by treatment of potentially correctable injurious processes such as hypocalcemia,
hypoglycemia and electrolyte disturbances, etiology specific therapies and
antiepileptic drug (AED) therapy. Phenobarbital remains the first line AED
therapy. Pharmacokinetic data on newer drugs is limited. Prognosis depends on the
etiology, seizure type, neurological examination at discharge and EEG. Long term
neurodevelopmental follow up is essential for babies with neonatal seizures.
PMID- 25124330
TI - Protective effects of intranasal immunization with recombinant glycoprotein d in
pregnant BALB/c mice challenged with different strains of equine herpesvirus 1.
AB - Equine herpesvirus (EHV)-1 induces respiratory infection, neurological disorders
and abortion in horses. Most of the currently available attenuated or inactivated
vaccines against this infection are administered intramuscularly and only provide
partial protection against the respiratory disease. The present study examines
the effect of intranasal immunization with purified EHV-1 recombinant
glycoprotein D (gD) in BALB/c mice followed by challenge with three different EHV
1 strains during early to mid-pregnancy. The induced viral infection was
evaluated by virus isolation, DNA detection by polymerase chain reaction,
histopathology and immunohistochemical localization of antigen in the lung,
placenta and uterus. Non-immunized mice showed clinical signs of infection,
positive virus isolation from lungs and uteri, and abortion induced by one of the
virus strains. Endometrial lesions developed in some of these animals that have
been described previously only in horses. Immunized mice and their offspring had
no viral infection or typical lesions. Intranasally administered gD therefore
induced partial or complete protection against three different EHV-1 strains in
BALB/c mice.
PMID- 25124331
TI - Oxidative modification, inflammation and amyloid in the normal and diabetic cat
pancreas.
AB - The pathogenesis of beta-cell dysfunction leading to pancreatic beta-cell failure
seen in type 2 diabetes mellitus is incompletely understood. Pancreatic tissues
were collected from nine control cats and nine diabetic cats and labelled
immunohistochemically to examine expression of interleukin (IL)-1beta, insulin,
islet amyloid polypeptide (IAPP) and 4-hydroxynonenal (4-HNE). Thioflavin-S was
used to stain for amyloid. All control cats showed positive labelling for IL
1beta and 4-HNE. Diabetic cats showed varying degrees of inflammation and
oxidative modification, owing in large part to the very small amount of islet
structure remaining in the typical diabetic cat pancreas. Amyloid deposition was
identified in 8/9 diabetic cats and 1/9 control cats. In order to validate these
findings, paired biopsy samples taken from an additional group of cats enrolled
in a study of obesity and hyperglycaemia (sampling at baseline and after 8-16
weeks of obesity and hyperglycaemia) were labelled for IL-1beta and 4-HNE. A
similar pattern of labelling was identified in the baseline samples to that seen
in control cats. A significant increase in IL-1beta and 4-HNE expression was seen
after a period of hyperglycaemia and obesity. Taken together, these findings
suggest that while present in normal cats, markers of inflammation and oxidative
modification increase very early during the development of disease. Future
studies focusing on these earlier time points are needed to understand the
factors that function in protection of the islet beta cell and the development of
islet pathology in type 2 diabetes mellitus in the cat.
PMID- 25124332
TI - Candidate selection for quadrant-based focal ablation through a combination of
diffusion-weighted magnetic resonance imaging and prostate biopsy.
AB - OBJECTIVES: To identify prostatic quadrants that could be preserved without
intervention, using diffusion-weighted magnetic resonance imaging (DWI) and
extended core biopsy, as a step toward implementation of quadrant-based focal
ablation with potential preservation of erectile and ejaculatory functions, based
on comparisons with unilateral hemi-gland ablation. PATIENTS AND METHODS: We
conducted a prebiopsy DWI study including 648 quadrants in 162 men who underwent
14-core biopsy including anterior sampling and radical prostatectomy (RP) for
localised cancer. Imaging and pathology were analysed on a quadrant basis. Each
quadrant was assessed through four-core sampling. Predictive performance of DWI
and biopsy for quadrant status was analysed. RESULTS: On RP specimens, 170
anterior (52.5%) and 172 posterior quadrants (53.1%) harboured significant
cancer. Negative predictive values of DWI, biopsy, and their combination for
significant cancer were 79.7%, 70.6%, and 91.1%, respectively, in anterior
quadrants, and 78.5%, 81.3%, and 91.7%, respectively, in posterior quadrants. DWI
incrementally improved the negative predictive values of biopsy in anterior (P <
0.001) and posterior quadrants (P = 0.025), without untoward impacts on positive
predictive values. Negative findings on both DWI and biopsy were identified in
posterior quadrants of 109 sides (33.6%), but in entire hemi-glands of 54 sides
(16.7%). CONCLUSIONS: The combination of DWI and 14-core biopsy including
anterior sampling efficiently identifies quadrants without significant cancer in
men with localised prostate cancer; the remaining quadrants, therefore, could be
potential candidate areas for focal ablation. Focal therapy designed based on
quadrant-based assessment could be superior to unilateral hemi-gland ablation for
preservation of posterior quadrants and retaining of sexual function in more
sides.
PMID- 25124334
TI - Progress toward the total synthesis of N-methylwelwitindolinone B isothiocyanate.
AB - Progress toward the welwitindolinone alkaloid N-methylwelwitindolinone B
isothiocyanate is reported. A key reaction to synthesize the [4.3.1] bicycle
embedded in the core of the molecule is a furan type 2 intramolecular Diels-Alder
reaction with a tetrasubstituted dienophile, which sets the two vicinal
quaternary centers present in the natural product. The sterically encumbered
cycloaddition precursor was synthesized using a Horner-Wadsworth-Emmons reaction
followed by a Suzuki cross-coupling reaction. Finally, introduction of the
secondary alkyl chloride was achieved by a regio- and diastereoselective opening
of a [2.2.1] oxobicycloheptane functionality.
PMID- 25124333
TI - Association of G-quadruplex forming sequences with human mtDNA deletion
breakpoints.
AB - BACKGROUND: Mitochondrial DNA (mtDNA) deletions cause disease and accumulate
during aging, yet our understanding of the molecular mechanisms underlying their
formation remains rudimentary. Guanine-quadruplex (GQ) DNA structures are
associated with nuclear DNA instability in cancer; recent evidence indicates they
can also form in mitochondrial nucleic acids, suggesting that these non-B DNA
structures could be associated with mtDNA deletions. Currently, the multiple
types of GQ sequences and their association with human mtDNA stability are
unknown. RESULTS: Here, we show an association between human mtDNA deletion
breakpoint locations (sites where DNA ends rejoin after deletion of a section)
and sequences with G-quadruplex forming potential (QFP), and establish the
ability of selected sequences to form GQ in vitro. QFP contain four runs of
either two or three consecutive guanines (2G and 3G, respectively), and we
identified four types of QFP for subsequent analysis: intrastrand 2G, intrastrand
3G, duplex derived interstrand (ddi) 2G, and ddi 3G QFP sequences. We analyzed
the position of each motif set relative to either 5' or 3' unique mtDNA deletion
breakpoints, and found that intrastrand QFP sequences, but not ddi QFP sequences,
showed significant association with mtDNA deletion breakpoint locations.
Moreover, a large proportion of these QFP sequences occur at smaller distances to
breakpoints relative to distribution-matched controls. The positive association
of 2G QFP sequences persisted when breakpoints were divided into clinical
subgroups. We tested in vitro GQ formation of representative mtDNA sequences
containing these 2G QFP sequences and detected robust GQ structures by UV-VIS and
CD spectroscopy. Notably, the most frequent deletion breakpoints, including those
of the "common deletion", are bounded by 2G QFP sequence motifs. CONCLUSIONS: The
potential for GQ to influence mitochondrial genome stability supports a high
priority investigation of these structures and their regulation in normal and
pathological mitochondrial biology. These findings emphasize the potential
importance of helicases that subsequently resolve GQ to maintain the stability of
the mitochondrial genome.
PMID- 25124335
TI - Incidence of retinopathy of prematurity in southwestern China and analysis of
risk factors.
AB - BACKGROUND: The aim of this study was to screen for retinopathy of prematurity
(ROP) in southwestern China and understand the prevalence and risk factors of
ROP, which may provide evidence useful in the prevention and treatment of ROP.
MATERIAL/METHODS: 1864 preterm infants (gestational age of <37 weeks and birth
weight of <=2500 g) underwent ROP screening from January 2009 to November 2012 in
Southwest China. The medical information of infants during perinatal period was
reviewed, and risk factors of ROP were determined. A total of 1614 infants were
recruited for final analysis. RESULTS: Incidence of ROP was 12.8%. The first,
second, third, and fourth stage of ROP was found in 64.6%, 29.6%, 3.4%, and 0.5%
of infants, respectively. No fifth stage of ROP was observed. In addition, 7.7%
of infants required surgical intervention. In our Department of Neonatology, the
incidence of ROP was 20.0%, which was significantly higher than in non
hospitalized patients (9.9%). The incidence of ROP remained unchanged over the
years. Independent risk factors of ROP included low birth weight (p=0.049), low
gestational age (p=0.008), days of oxygen supplementation (p=0.008), and
myocardial injury after birth (p=0.001). CONCLUSIONS: The prevalence of ROP in
preterm infants is relatively high in Southwest China, and low birth weight, low
gestational age, days of oxygen supplementation, and myocardial injury after
birth are independent risk factors for ROP.
PMID- 25124337
TI - Carbazole-based hole-transport materials for efficient solid-state dye-sensitized
solar cells and perovskite solar cells.
AB - Two carbazole-based small molecule hole-transport materials (HTMs) are
synthesized and investigated in solid-state dye-sensitized solar cells (ssDSCs)
and perovskite solar cells (PSCs). The HTM X51-based devices exhibit high power
conversion efficiencies (PCEs) of 6.0% and 9.8% in ssDSCs and PSCs, respectively.
These results are superior or comparable to those of 5.5% and 10.2%,
respectively, obtained for the analogous cells using the state-of-the-art HTM
Spiro-OMeTAD.
PMID- 25124336
TI - Sedentary behaviors, physical activity behaviors, and body fat in 6-year-old
children: the generation R study.
AB - BACKGROUND: Childhood overweight and obesity is a major public health concern.
Knowledge on modifiable risk factors is needed to design effective intervention
programs. This study aimed to assess associations of children's sedentary
behaviors (television viewing and computer game use) and physical activity
behaviors (sports participation, outdoor play, and active transport to/from
school) with three indicators of body fat, i.e., percent fat mass, body mass
index (BMI) standard deviation scores, and weight status (normal weight,
overweight). METHODS: Cross-sectional data from 5913 6-year-old ethnically
diverse children were analyzed. Children's weight and height were objectively
measured and converted to BMI. Weight status was defined according to age- and
sex-specific cut-off points of the International Obesity Task Force. BMI standard
deviation scores were created, based on Dutch reference growth curves. Fat mass
was measured my dual-energy X-ray absorptiometry (DXA). Sedentary and physical
activity behaviors were assessed by parent-reported questionnaires. Series of
logistic and linear regression analyses were performed, controlling for
confounders (i.e., socio-demographic factors, family lifestyle factors, and other
sedentary behaviors and physical activity behaviors). RESULTS: Sports
participation was inversely associated with fat mass (p < 0.001), even after
adjustment for socio-demographic factors, family lifestyle factors, and other
sedentary behaviors and physical activity behaviors. No other independent
associations were observed. CONCLUSIONS: The results of this study indicate that
sports participation is inversely associated with percent body fat among
ethnically diverse 6-year-old children. More research in varied populations
including objective measurements and longitudinal designs are needed to confirm
these current results.
PMID- 25124338
TI - Adult neurogenesis: bridging the gap between mice and humans.
AB - Neural stem/progenitor cells (NSPCs) generate new neurons in the mammalian brain
throughout life. Over the past two decades, substantial progress has been made in
deciphering the cellular and molecular mechanisms underlying adult neurogenesis
and in understanding the role played by new neurons in brain function in animal
models of health and disease. By contrast, knowledge regarding the extent and
relevance of neurogenesis in the adult human brain remains scant. Here we review
new concepts about how new neurons shape adult brain circuits, discuss
fundamental, unanswered questions about stem cell-associated neural plasticity,
and illustrate how the gap between the animal-based basic research and current
efforts to analyze life-long neuronal development of the human brain may be
overcome by using novel experimental strategies.
PMID- 25124339
TI - Association between mental health disorders and sexual dysfunction in patients
suffering from rheumatic diseases.
AB - INTRODUCTION: Sexual functioning may be notoriously affected in patients
suffering from rheumatic diseases, yet the extent to which physical and/or
psychological factors contribute to sexual dysfunction in this particular group
of patients remains underinvestigated. AIM: This cross-sectional study aimed at
investigating whether an association exists between psychological status
(anxiety, depression) and sexual dysfunction, independently of other physical
factors, in patients with rheumatic disorders. METHODS: A total of 509
consecutive rheumatologic patients, aged 54.7 +/- 14.2 years, 423 female and 86
male, were studied. Female and male sexual function was evaluated with the Female
Sexual Dysfunction Index (FSFI) and the International Index of Erectile Function
(IIEF) questionnaire, respectively. The Hamilton Anxiety Scale and the Zung Self
Rating Depression Scale were used to detect presence of anxiety and depression,
respectively. MAIN OUTCOME MEASURES: Sexual dysfunction affected 69.9%, anxiety
37.5%, and depression 22% of our patients. RESULTS: A strong and negative
correlation was found between anxiety and both FSFI (r = -0.169, P < 0.001) and
IIEF score (r = -0.304, P = 0.004). Similarly, depressive symptomatology was
strongly and negatively correlated with both FSFI (r = -0.178, P < 0.001) and
IIEF score (r = -0.222, P = 0.04). In the logistic regression analysis, apart
from increasing age and female sex, depression (P = 0.027) and anxiety (P =
0.049) were identified as the only predictors of sexual dysfunction, even after
adjustment for a variety of physical factors. CONCLUSIONS: Mental distress and
sexual dysfunction are extremely common in rheumatologic patients. Sexual
dysfunction is significantly associated with anxiety and depression in both men
and women and may be independently predicted by their presence in this group of
patients. Physicians dealing with rheumatologic patients should be aware of these
results and incorporate screening and treatment of the above comorbidities in the
global assessment of their patients, in order to alleviate the disease-emerging
mental and physical burden and improve their quality of life.
PMID- 25124340
TI - Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids,
gabapentinoids and their combinations: a topical review.
AB - In contemporary post-operative pain management, patients are most often treated
with combinations of non-opioid analgesics, to enhance pain relief and to reduce
opioid requirements and opioid-related adverse effects. A diversity of
combinations is currently employed in clinical practice, and no well-documented
'gold standards' exist. The aim of the present topical, narrative review is to
provide an update of the evidence for post-operative analgesic efficacy with the
most commonly used, systemic non-opioid drugs, paracetamol, non-steroidal anti
inflammatory drugs (NSAIDs)/COX-2 antagonists, glucocorticoids, gabapentinoids,
and combinations of these. The review is based on data from previous systematic
reviews with meta-analyses, investigating effects of non-opioid analgesics on
pain, opioid-requirements, and opioid-related adverse effects. Paracetamol,
NSAIDs, COX-2 antagonists, and gabapentin reduced 24 h post-operative morphine
requirements with 6.3 (95% confidence interval: 3.7 to 9.0) mg, 10.2 (8.7, 11.7)
mg, 10.9 (9.1, 12.8) mg, and >= 13 mg, respectively, when administered as
monotherapy. The opioid-sparing effect of glucocorticoids was less convincing,
2.33 (0.26, 4.39) mg morphine/24 h. Trials of pregabalin > 300 mg/day indicated a
morphine-sparing effect of 13.4 (4, 22.8) mg morphine/24 h. Notably, though, the
available evidence for additive or synergistic effects of most combination
regimens was sparse or lacking. Paracetamol, NSAIDs, selective COX-2 antagonists,
and gabapentin all seem to have well-documented, clinically relevant analgesic
properties. The analgesic effects of glucocorticoids and pregabalin await further
clarification. Combination regimens are sparsely documented and should be further
investigated in future studies.
PMID- 25124341
TI - Comparison of the ocular characteristics of anterior uveitis caused by herpes
simplex virus, varicella-zoster virus, and cytomegalovirus.
AB - PURPOSE: To compare the clinical characteristics of anterior uveitis (AU) caused
by herpes simplex virus (HSV), varicella-zoster virus (VZV), or cytomegalovirus
(CMV). METHODS: The medical records were reviewed of 46 patients whose diagnoses
were based on their clinical characteristics [e.g., unilateral involvement,
presence of keratic precipitates (KPs), and elevation of intraocular pressure
(IOP)] and on PCR detection of herpes virus DNA in the aqueous humor. The
demographics, chief complaints, and clinical characteristics of the three types
of herpetic AU were compared. RESULTS: Of the 46 patients with AU, eight had HSV
AU, 20 had VZV-AU, and 18 had CMV-AU. HSV-AU and VZV-AU shared common features,
i.e., a relatively acute disease process and the presence of large KPs. Among the
three groups of patients, the characteristic features of those with VZV-AU were
severe intraocular inflammation, as shown by severe aqueous flare, highest viral
load in the aqueous humor, and presence of segmental iris atrophy. In comparison,
patients with CMV-AU had the mildest intraocular inflammation, lowest corneal
endothelial cell density, and highest IOP. CONCLUSIONS: Although the AU caused by
each of the three types of herpes viruses has a number of common features, each
disease also has distinct features that should facilitate an accurate diagnosis.
PMID- 25124344
TI - [A quantitative approach to sports training-adapted social determinants
concerning sport].
AB - OBJECTIVE: Identifying and quantitatively analysing social determinants affecting
disabled teenagers' inclusion/exclusion in high-performance sports. METHOD: This
was a descriptive cross-sectional study involving 19 12- to 19-year-old athletes
suffering physical and sensory disability and 17 staff from the District
Institute of Recreation and Sport. Likert-type rating scales were used, based on
four analysis categories, i.e. social structure, socio-economic, educational and
living condition determinants. RESULTS: Social inequity pervades the national
paralympic sports' system. This is because 74 % of individuals only become
recognised as sportspeople when they have obtained meritorious results in set
competition without appropriate conditions having been previously provided by
such paralympic sports institution to enable them to overcome structural and
intermediate barriers. CONCLUSIONS: The social structure imposed on district
based paralympic sport stigmatises individuals regarding their individual
abilities, affects their empowerment and freedom due to the discrimination
experienced by disabled teenagers regarding their competitive achievements.
PMID- 25124343
TI - Genetics of metabolic syndrome.
AB - Metabolic syndrome (MetS) is a cluster of metabolic traits associated with an
increased risk of cardiovascular disease and type 2 diabetes mellitus. Central
obesity and insulin resistance are thought to play key roles in the pathogenesis
of the MetS. The MetS has a significant genetic component, and therefore linkage
analysis, candidate gene approach, and genome-wide association (GWA) studies have
been applied in the search of gene variants for the MetS. A few variants have
been identified, located mostly in or near genes regulating lipid metabolism. GWA
studies for the individual components of the MetS have reported several loci
having pleiotropic effects on multiple MetS-related traits. Genetic studies have
provided so far only limited evidence for a common genetic background of the
MetS. Epigenetic factors (DNA methylation and histone modification) are likely to
play important roles in the pathogenesis of the MetS, and they might mediate the
effects of environmental exposures on the risk of the MetS. Further research is
needed to clarify the role of genetic variation and epigenetic mechanisms in the
development of the MetS.
PMID- 25124345
TI - [The association between socioeconomic indicators andadolescents'physical
activity and health-related fitness].
AB - OBJECTIVE: This study was aimed at analysing the association between
socioeconomic indicators and adolescents' physical activity and health-related
fitness. METHODS: The study involved 716 adolescents from both genders whose age
ranged from 10 to 18 years-old (46.8% male) who answered a questionnaire for
estimating their habitual physical activity, socioeconomic status; two health
related physical fitness tests were also performed. The socioeconomic indicators
analysed concerned their parents' educational level and the number of bathrooms,
TVs, cars, housemaids, refrigerators and freezers in their homes. RESULTS: A
positive association was found between paternal education (PR=1.61 (range 1.27
2.10) and 1.41 (1.10-1.83)) and housemaids (PR=1.97 (1.04-3.81) and 1.92 (1.05
3.52)) with recommended physical activity and leisure time physical activity,
respectively. The number of cars (PR=1.48: 1.02-2.19) and freezers (PR=1.88: 1.12
3.18) was positively associated with leisure time physical activity and the
number of TVs negatively so (PR=0.75: 0.63-0.89). The number of TVs (PR=0.80:
0.67-0.96) and cars (PR=0.70: 0.55-0.89) was negatively associated with
cardiorespiratory fitness whilst paternal education (PR=1.17: 1.00-1.37) and the
number of bathrooms in the home (PR=1.25: 1.02-1.54) were positively associated
with muscular strength. CONCLUSION: Physical activity and health-related physical
fitness were associated with socioeconomic status. However, such association
depended on the socioeconomic indicator being analysed. Caution should be taken
when analysing studies which use different socioeconomic indicators.
PMID- 25124346
TI - [Conceptual differences and praxiological implications concerning social
determination or social determinants].
AB - The differences between the social determination of health approach adopted by
the Latin-American Social Medicine and Collective Health movement and the WHO's
social determinants of health approach are not merely conceptual but involve
ethical and political considerations. Different notions of causality and risk are
implied in the aforementioned approaches and shape how concepts regarding health
illness and health inequity are understood and how they may be confronted. This
article attempts to clarify the praxiological implications of such approaches and
contextualise the approaches' socio-historical construction, address
epistemological, methodological and ontological differences and propose some
considerations regarding the praxiological implications.
PMID- 25124342
TI - Association of the degree of adiposity and duration of obesity with measures of
cardiac structure and function: the CARDIA study.
AB - OBJECTIVE: Examine whether there are independent influences of a greater degree
of adiposity and longer duration of obesity on cardiac structure and function.
METHODS: Participants of CARDIA were 18-30 years when they underwent a baseline
examination in 1985-86. Seven follow-up examinations were conducted every 2-5
years. RESULTS: Among 2,547 participants who underwent an echocardiogram at the
year 25 examination and were not obese at baseline, 34.4 and 35.5% were overall
(BMI >= 30 kg m(-2) ) and abdominally obese (waist circumference: men: >102 cm;
women: >88 cm) at year 25, respectively. A greater degree of overall and
abdominal adiposity at year 25 were each associated with a greater left
ventricular (LV) mass (P < 0.001), LV volume (P < 0.001), LV mass-to-volume ratio
(P < 0.001), left atrial dimension (P < 0.001), and ejection fraction (P < 0.05)
after adjustment for duration of obesity and other risk factors. In contrast, a
longer duration of overall obesity was associated with a greater LV mass (P =
0.003) and a trend for a lower ejection fraction (P = 0.07). CONCLUSIONS: A
greater degree of adiposity is strongly associated with concentric LV remodeling
in midlife, while the cumulative effects of a longer duration of overall obesity
during young adulthood contribute to concentric remodeling predominantly by
increasing LV mass.
PMID- 25124347
TI - [The relationship-based meaning of teenage pregnancy in Bogota regarding the
family system].
AB - OBJECTIVES: Ascertaining the meaning of teenage pregnancy for teenagers and their
immediate families. METHODOLOGY: This was an analytical, cross-sectional,
exploratory, qualitative study. Data was obtained through in-depth interviews
with 10 pregnant teenagers and their immediate families, plus a focus group
involving another 12 pregnant teenagers. RESULTS: Analysis by category revealed a
tenuous limit between adolescents' narrative identity and a lack of such identity
and identity based on the concept of family. Pregnancy provokes a series of
responses within families, including fear in a pregnant adolescent and her
partner, disappointment on the part of the parents, social isolation and eventual
acceptance and redefinition of such pregnancy. CONCLUSIONS: Pregnancy can provide
the means for an adolescent to redress a deficit in her emotional needs, such
condition keeping the family together at the expense of a teenager's emancipation
and may represent an intergenerational legacy.
PMID- 25124348
TI - [Elderly people's level of participation in social and recreational activities in
Barranquilla, Colombia].
AB - OBJECTIVE: Determining elderly people's level of participation in social and
recreational activities in Barranquilla, Colombia. METHODS: This was a
descriptive cross-sectional study involving 469 elderly people; a basic
activities of daily living scale, which had been adapted to the ongoing
activities being carried out in the pertinent scenarios, was used for evaluating
their level of participation in social and recreational activities. Bivariate
analysis was used for estimating the relationship between level of participation
and age-range and coexistence, using OR and chi2 tests. RESULTS: The scale
categorized 40.9 % of the subjects as having low participation and only 20.2 % as
actively and voluntarily participating in the activities being offered. There was
an increased risk of non-participation in social and recreational activities
regarding adults being over 80 years of age (OR 3.3: (2.2-4.9) 95 % CI) and those
living alone (OR 1.75: (1.09-2.82) 95 % CI). CONCLUSION: A clear trend towards
less participation was shown as aged increased; this is why social isolation
becomes a risk factor for this group of people's quality of life. It is
recommended that social networks promoting the elderly's health and quality of
life should thus be strengthened.
PMID- 25124349
TI - [Public schoolstudents' body composition and motor performance].
AB - OBJECTIVE: Analysing the influence of body composition on female public school
students' motor performance. METHODS: This was a cross-sectional study which
involved a sample 371 female public school system students aged seven to 16 years
old; they were placed ingroup 1 (G1), group 2 (G2) orgroup 3 (G3). Weight and
height were measured for evaluating the body mass index (BMI), triceps and
subscapular skinfold thickness for assessing the percentage of body fat (%BF).Sit
and reach and 20 meters displacement speed tests were also used. RESULTS:
Significant differences were found regarding all anthropometric variables
considered. It was found that 41.1% of the 371 female students were overweight or
obese (66.1 % in G1, 34.5% in G2 and 25.3 % in G3). Regarding % BF, 29.1% of the
students had percentages above suitable levels (23.3 % in G1, 23.8 % in G2 and
35.2 % in G3). Significant differences between G1 and G2 and between G2 and G3
were also found in the motor tests regarding the sit and reach test, as well as
between G1 and G3 in the speed test. CONCLUSION: Adiposity may have interfered
with the students' motor performance, especially regarding the 20 meters'
displacement speed test.
PMID- 25124350
TI - [Dental caries in young adults regarding saliva's microbiological and physical
chemical characteristics].
AB - OBJECTIVE: Determining the relationship between saliva's physicochemical
properties, cariogenic microorganism count, facultative anaerobic and gram
negative bacteria based on caries' experience in young adults. MATERIALS AND
METHODS: Stimulated whole saliva was collected from 120 students aged 17 to 34
years old for analysing salivary flow rate, pH, calcium and phosphate ion
concentration, lactic acid, cariogenic microorganism count and facultative and
gram-negative bacteria. RESULTS: Salivary flow rate was included in the
biological reference interval but was not found to be associated with caries; the
same thing happened regarding lactic acid. A direct relationship was found
between calcium and phosphate concentration and dental cavities. Streptococcus
mutans was associated with white spot lesion whereas Lactobacillus spp.,
facultative anaerobic and gram-negative bacteria were associated with advanced
cavities. CONCLUSIONS: Saliva's physicochemical and microbiological
characteristics in the young adult group evaluated here were differentially
related to caries in different degrees of progress.
PMID- 25124351
TI - [The relationship between the oral health and socioeconomic characteristics of
chronic kidney disease patients undergoing haemodialysis treatment or kidney
transplant].
AB - OBJECTIVE: Characterising the oral health of patients undergoing different types
of dialysis or kidney transplant. MATERIALS AND METHODS: This was a descriptive
study which involved multivariate analysis of information taken from an initial
database regarding 336 patients; 49 % were receiving haemodialysis, 34 %
peritoneal dialysis, 7 % pre-dialysis and 10 % kidney transplant. Illustrative
variables were age, gender, marital status, occupation, education, oral hygiene
and gingival indexes, flossing, decayed, missing, and filled teeth (DMFT) index,
renal disease aetiology and type of dialysis being received. A hierarchical
clustering method was used. RESULTS: Four groups of patients were identified.
Class 1 (37.8 %) consisted of unmarried men having had secondary education and
having good oral hygiene, very high DMFT, with haemodialysis but no
stomatological pathology. Class 2 (20.24 %) included haemodialysis patients who
had received elementary education, were unemployed, had inadequate oral hygiene,
severe gingivitis, very high DMF rate and high Candida frequency. Class 3 (31.2
%) included women undergoing peritoneal dialysis who were over 70 years old, had
received elementary education, were housewives, edentulous and who had loss of
vertical dimension. Class 4 (10.7 %) included men who had received renal
transplant, secondary education and were employees; one third of them were
edentulous and had soft tissue alterations. CONCLUSION: Multivariate analysis
indicated a possible relationship between the type of dialysis received and
patients' socioeconomic characteristics regarding oral health status.
PMID- 25124352
TI - Occupational exposure to air pollutants: particulate matter and respiratory
symptoms affecting traffic-police in Bogota.
AB - OBJECTIVES: Quantifying personal exposure to particles less than 10 micrometres
in diameter (PM10) and determining the prevalence of respiratory symptoms in
traffic-police officers working in Bogota's metropolitan area. METHODS: This was
a cross-sectional study of 574 traffic-police officers divided into two groups
(477 traffic-police and 97 police working in an office). They were given a
questionnaire inquiring about respiratory symptoms, toxicological medical
evaluation, lung function tests and personal PM10 monitoring. The differences
between groups were found using stratified analysis (i.e. comparing odds ratios).
Multivariate analysis of factors related to symptoms and diagnosis of respiratory
alteration was also performed. RESULTS: Respiratory symptoms concerned a higher
prevalence of cough, expectoration and rhinosinusitis in the traffic-police
group. Medical examination revealed that the traffic-police group had higher
nasal irritation prevalence; lung function tests showed no difference. Mean PM10
levels were higher for the traffic-police group (139.4 MUg/m3), compared to the
office work group (86.03 MUg/m3). DISCUSSION: PM10 values in both groups did not
exceed allowable limits for respirable particles in the workplace according to
ACGIH standards. Traffic-police exposed to air pollution had an increased risk of
developing respiratory symptoms and signs, thereby agreeing with the results of
this and other studies. Personal monitoring is a valuable tool when quantifying
the concentration of PM10to which an individual has been exposed during a normal
workday. This study contributes towards further research in to the effects of
PM10 in populations at risk.
PMID- 25124353
TI - [Population exposure to mercury in the municipality of San Marcos (Sucre
department) due to eating contaminated rice (Oryza sativa)].
AB - OBJECTIVE: Determining the magnitude of mercury exposure in the population living
in the municipality of San Marcos due to eating contaminate drice (Oryza sativa).
METHODS: Twenty people (representative of the population) were selected, as were
food (raw rice) and hair samples for determining total mercury and methyl mercury
by cold vapour atomic absorption spectrophotometry. Student's t-test was used for
comparing different samples (p<0.05 significance level) and correlation was
analysed for determining the relationship between consumption habits and mercury
concentration in humans. RESULTS: Rice sold loose (i.e. unpackaged San Marcos
white rice) was the only sample having 0.021 mg/g minimum total mercury
concentration, whilst rice sold in packaged form yielded no measurable value.
Only 5% of the population sample exceeded the US Environmental Protection
Agency's (EPA) 0.1 mg/kg bw/day reference dose (RfD) for Me Hg ingestion (RfD).
CONCLUSIONS: The HgT exposure of people living in and around San Marcos
concerning rice consumption was low and did not involve great risks to their
health. However, frequent consumption of other types of contaminated food could
pose a potential threat to the consumers' health, meaning that ongoing
environmental monitoring is necessary.
PMID- 25124354
TI - [Central venous catheter-related complications in critically ill children].
AB - OBJECTIVE: Placing central venous catheters is essential when managing critically
ill children. This paper was thus aimed at identifying the major complications
involved in this and determining the incidence of mechanical and infection
related complications associated with central venous catheterization in
critically ill children. MATERIAL AND METHODS: A descriptive study was undertaken
between October 2011 and March 2012 of all new central venous catheters inserted
in critically ill children. The definition of central venous catheter infection
was based on CDC criteria. RESULTS: During the study period 200 central venous
catheters were placed, 51 % in male patients, mostly infants; 71 % required
mechanical ventilation and 56.5 % medication for hemodynamic support. Respiratory
tract infections were the leading diagnosis on admission in 33 % of the cases.
Complications were reported in 8.5 % of the children (52 % of these being due to
mechanical complication and 48 % to infection). Mechanical complication incidence
was 4.5% and eight central venous catheters fulfilled CDC criteria for central
line associated blood stream infection (4 % incidence, i.e. 5 per 1,000
catheter/day rate). CONCLUSIONS: Despite some complications arising from its use,
central venous catheter placement is a safe procedure. Mechanical and infection
incidence associated with central venous catheter placement should be known, not
only because it differs from that regarding adult patients but also because this
can help to establish preventative measures for reducing such complications and
improving the care of critically ill children.
PMID- 25124355
TI - [HIV/AIDS prevalence in Medellin and presumptive test diagnostic accuracy (2006
2012)].
AB - OBJECTIVE: Determining HIV/AIDS prevalence in Medellin, Colombia, and its
association with demographic factors2006-2012,as well as exploring screening test
performance. METHODS: This was a cross-sectional study involving 5,851subjects.
Descriptive statistics were used to describe the population (i.e. frequencies and
summary measures); infection prevalence was calculated and its association with
demographic factors identified by using parametric and non-parametric statistical
tests, prevalence ratios and odds ratios. Predictive values were calculated, as
were the percentage of false results and percentage of subjects correctly
diagnosed. RESULTS: Mean age was 27 years old (0 to 94 year range); 70.5% of the
population were female. HIV/AIDS prevalence was found to be 1.8% during the study
period (0.32% annually). A statistical association was found with gender and age,
a higher prevalence being found in males and adults. The false positive rate was
0.7%, negative predictive value100%, positive predictive value 71% and there was
99% overall efficiency. CONCLUSION: HIV/AIDS prevalence found in this study was
significantly higher than that found in other studies in the Antioquia department
and for Colombia overall. The male and female infection prevalence ratio revealed
increased diagnosis in women. The screening test performed well in areas having
less than 1% infection prevalence.
PMID- 25124356
TI - [Mathematical modelling of an infectious disease in a prison setting and optimal
preventative control strategies].
AB - A mathematical model was constructed for modelling transmission dynamics and the
evolution of an infectious disease in a prison setting, considering asymptomatic
infectious people, symptomatic infectious people and isolated infectious people.
The model was proposed as a nonlinear differential equation system for describing
disease epidemiology. The model's stability was analysed for including a
preventative control strategy which would enable finding a suitable basic
reproduction number-based control protocol. A cost function related to the system
of differential equations was formulated to minimise infectious populations and
intervention costs; such function was minimised by using the Pontryagin maximum
principle which determines optimum preventative control strategies by minimising
both infectious populations and associated costs. A numerical analysis of the
model was made, considering preventative control effectiveness levels and
different control weighting constants. Conclusions were drawn. The basic
reproduction number characterises system stability and leads to determining clear
control criteria; a preventative control threshold was defined, based on the
controlled basic reproduction number which enabled deducing that disease control
requires uniform preventative control involving high rates of effectiveness.
PMID- 25124357
TI - Iron speciation in beans (Phaseolus vulgaris) biofortified by common breeding.
AB - The iron storage protein ferritin is a potential vehicle to enhance the iron
content of biofortified crops. With the aim of evaluating the potential of
ferritin iron in plant breeding, we used species-specific isotope dilution mass
spectrometry to quantify ferritin iron in bean varieties with a wide range of
total iron content. Zinc, phytic acid, and polyphenols were also measured. Total
iron concentration in 21 bean varieties ranged from 32 to 115 ppm and was
positively correlated with concentrations of zinc (P = 0.001) and nonferritin
bound iron (P < 0.001). Ferritin iron ranged from 13% to 35% of total iron and
increased only slightly in high iron beans (P = 0.007). Concentrations of
nonferritin bound iron and phytic acid were correlated (P = 0.001), although
phytic acid:iron molar ratio decreased with increasing iron concentration (P =
0.003). Most iron in high iron beans was present as nonferritin bound iron, which
confirms our earlier finding showing that ferritin iron in beans was lower than
previously published. As the range of ferritin iron content in beans is
relatively narrow, there is less opportunity for breeders to breed for high
ferritin. The relevance of these findings to the extent of iron absorption
depends on resolving the question of whether ferritin iron is absorbed or not to
a greater extent than nonferritin bound iron.
PMID- 25124358
TI - Comparatively examining of the apelin-13 levels in the Capoeta trutta (Heckel,
1843) and Cyprinus carpio (Linnaeus, 1758).
AB - Apelin is a recently discovered peptide produced by several tissues in the
various vertebrates and fish. Apelin has been suggested to have role in
regulation of many diverse physiological functions including food intake, energy
homoeostasis, immunity, osmoregulation and reproduction. In this study, apelin-13
levels in the blood serum of Cyprinus carpio and Capoetta trutta were determined.
Then the results were compared between two species and sexes of each species.
Apelin-13 level was analysed using the enzyme-linked immunoassay (ELISA) kit (Rat
apelin-13 ELISA kit, catalog no: CSB-E14367r). Apelin-13 level in the blood serum
of C. trutta was significantly higher than those of the C. carpio (p < 0.05).
However, its levels were observed to be no significant difference (p > 0.05) that
compared to between sexes of each species. There was a significant negative
correlation (r = -0.829, p = 0.0001) between the apelin-13 level and body weight
of C. carpio. However, no significant correlation (r = -0.022, p = 0.924) between
the apelin-13 level and weight of C. trutta observed.
PMID- 25124360
TI - Antiplatelet therapy before, during, and after extremity revascularization.
AB - Peripheral arterial disease (PAD) is well recognized as a marker for systemic
atherosclerosis. Platelets play an essential role in all stages of the disease,
contributing to both thrombosis and the development of atherosclerosis.
Medication regimens to optimize outcomes in both patients who are to undergo
revascularization and those who will be managed without interventional therapy
must address antiplatelet therapy. Given the common cardiovascular and
cerebrovascular comorbidities in patients with PAD, antiplatelet therapy has the
potential to decrease thromboembolic events in addition to improving patency
after interventions. This clinical update reviews the current literature and
recommendations for antiplatelet therapy in patients with PAD.
PMID- 25124359
TI - Preoperative dietary restriction reduces intimal hyperplasia and protects from
ischemia-reperfusion injury.
AB - OBJECTIVE: Whereas chronic overnutrition is a risk factor for surgical
complications, long-term dietary restriction (reduced food intake without
malnutrition) protects in preclinical models of surgical stress. Building on the
emerging concept that acute preoperative dietary perturbations can affect the
body's response to surgical stress, we hypothesized that short-term high-fat diet
(HFD) feeding before surgery is detrimental, whereas short-term nutrient/energy
restriction before surgery can reverse negative outcomes. We tested this
hypothesis in two distinct murine models of vascular surgical injury, ischemia
reperfusion (IR) and intimal hyperplasia (IH). METHODS: Short-term overnutrition
was achieved by feeding mice a HFD consisting of 60% calories from fat for 2
weeks. Short-term dietary restriction consisted of either 1 week of restricted
access to a protein-free diet (protein/energy restriction) or 3 days of water
only fasting immediately before surgery; after surgery, all mice were given ad
libitum access to a complete diet. To assess the impact of preoperative nutrition
on surgical outcome, mice were challenged in one of two fundamentally distinct
surgical injury models: IR injury to either kidney or liver, or a carotid focal
stenosis model of IH. RESULTS: Three days of fasting or 1 week of preoperative
protein/energy restriction attenuated IH development measured 28 days after focal
carotid stenosis. One week of preoperative protein/energy restriction also
reduced plasma urea, creatinine, and damage to the corticomedullary junction
after renal IR and decreased aspartate transaminase, alanine transaminase, and
hemorrhagic necrosis after hepatic IR. However, exposure to a HFD for 2 weeks
before surgery had no significant impact on kidney or hepatic function after IR
or IH after focal carotid stenosis. CONCLUSIONS: Short-term dietary restriction
immediately before surgery significantly attenuated the vascular wall
hyperplastic response and improved IR outcome. The findings suggest plasticity in
the body's response to these vascular surgical injuries that can be manipulated
by novel yet practical preoperative dietary interventions.
PMID- 25124361
TI - Standard endovascular treatment of abdominal aortic aneurysms in patients with
very short proximal necks using the Endurant stent graft.
AB - OBJECTIVE: This study evaluated and compared the midterm results of endovascular
aortic aneurysm repair with the Endurant (Medtronic Inc, Santa Rosa, Calif) stent
graft system in off-label use in patients with short (<10 mm) proximal aortic
necks and in patients treated according to device-specific instructions for use.
METHODS: This was a case-control (2:1) single-center retrospective analysis of
prospectively collected data performed between September 2008 and December 2012.
Analysis identified 19 elective patients with short (<10 mm) proximal necks and
mild angulations (<=45 degrees ) treated with the Endurant stent graft and 38
patients matched for age, sex, and aneurysm diameter with proximal aortic necks
>=10 mm in length who met the instructions for use. End points included technical
and clinical success and freedom from any secondary intervention, any type of
endoleak, and aneurysm-related death. RESULTS: The short-neck group was a mean +/
standard deviation age of 71.7 +/- 8.9 years, 84% were men, and their mean
infrarenal aortic neck length was 6.1 +/- 1.2 mm. Mean suprarenal and infrarenal
angles were 110 degrees +/- 10.4 degrees and 170 degrees +/- 15.4 degrees ,
respectively. Aortic neck diameters were similar between the groups (26.6 +/- 3.8
vs 25.7 +/- 3.7 mm; P = .36). Primary technical success was achieved in all
cases. Off-label patients were more likely to require additional proximal cuff
deployment to successfully obtain a seal (21% vs 3%; P = .04). The two patient
groups were similar in rates of perioperative mortality, morbidity, and
complications. Mean follow-up of 24 +/- 12 months revealed no differences in
clinical success, freedom from reintervention, and aneurysm-related death. No
type I endoleaks were observed in either group during the follow-up period.
CONCLUSIONS: The Endurant stent graft system applied off-label in patients with
very short aneurysm necks (<10 mm) with mild angulation showed acceptable
treatment results. These midterm results might suggest its use in carefully
selected patients with very short neck anatomy. Long-term data are needed to
verify the observed durability of the Endurant stent graft.
PMID- 25124362
TI - Glucose-lowering effect of insulin degludec is independent of subcutaneous
injection region.
AB - BACKGROUND AND OBJECTIVES: Patients with diabetes mellitus inject insulin in
different regions of the body. This study investigated the pharmacokinetic and
pharmacodynamic properties of insulin degludec (IDeg), a new-generation once
daily basal insulin with an ultra-long duration of action, after subcutaneous
(SC) administration in different injection regions. METHODS: In this study, 20
healthy subjects received single SC doses of IDeg (0.4 U/kg; separated by 13-21
days) in the thigh, abdomen and deltoid in a randomised, open-label, single
centre, single-dose, complete crossover trial. Each dose was followed by a 24-h
euglycaemic clamp and 120-h pharmacokinetic blood sampling. The obtained
pharmacokinetic/pharmacodynamic profiles were extrapolated to steady state by
simulation using a pharmacokinetic/pharmacodynamic model. RESULTS: Total IDeg
exposure [area under the IDeg serum concentration-time curve 0-120 h after a
single dose (AUCIDeg,0-120h,SD)] and maximum serum concentration [maximum IDeg
serum concentration after a single dose (C max,IDeg,SD)] were higher (6-7 and 23
27 %, respectively) following a single SC dose in the deltoid or abdomen,
compared with the thigh, as also observed with other insulin preparations. No
statistical difference was observed in these measures between deltoid and
abdominal administration. No pronounced differences were observed in the glucose
lowering effect of IDeg [area under the glucose infusion rate (GIR) curve 0-24 h
after a single dose (AUCGIR,0-24h,SD) and maximum GIR after a single dose
(GIRmax,SD)] when injected in the thigh, abdomen or deltoid (AUCGIR,0-24h,SD
2,572, 2,833 and 2,960 mg/kg, respectively). Simulated mean steady-state
pharmacokinetic and pharmacodynamic profiles supported a flat and stable IDeg
exposure and effect regardless of injection region, with comparable total glucose
lowering effects [area under the GIR curve at steady state (AUCGIR,tau,SS)]
between the thigh, abdomen and deltoid. CONCLUSIONS: These findings support
administering IDeg SC in the thigh, upper arm or abdominal wall without affecting
IDeg absorption or effect at steady state.
PMID- 25124364
TI - [How can we improve the care of patients with benign anorectal diseases?].
PMID- 25124363
TI - Cross-platform comparison of nucleic acid hybridization: toward quantitative
reference standards.
AB - Measuring interactions between biological molecules is vitally important to both
basic and applied research as well as development of pharmaceuticals. Although a
wide and growing range of techniques is available to measure various kinetic and
thermodynamic properties of interacting biomolecules, it can be difficult to
compare data across techniques of different laboratories and personnel or even
across different instruments using the same technique. Here we evaluate relevant
biological interactions based on complementary DNA and RNA oligonucleotides that
could be used as reference standards for many experimental systems. We measured
thermodynamics of duplex formation using isothermal titration calorimetry,
differential scanning calorimetry, and ultraviolet-visible (UV-vis) monitored
denaturation/renaturation. These standards can be used to validate results,
compare data from disparate techniques, act as a teaching tool for laboratory
classes, or potentially to calibrate instruments. The RNA and DNA standards have
many attractive features, including low cost, high purity, easily measurable
concentrations, and minimal handling concerns, making them ideal for use as a
reference material.
PMID- 25124366
TI - Properties of starch from potatoes differing in glycemic index.
AB - Potatoes are a popular source of dietary carbohydrate worldwide and are generally
considered to be a high glycemic index (GI) food. Potato starch characteristics
play a key role in determining their rate of digestion and resulting glycemic
response. Starches isolated from seven potato cultivars with different GI values,
including a low GI cultivar (Carisma), were examined for relative crystallinity,
granule size distribution, amylopectin chain length, and thermal and pasting
properties. Starch from the Carisma cultivar was more thermally stable and more
resistant to gelatinization, with significantly higher (p < 0.05) pasting
temperature and differential scanning calorimetry (DSC) gelatinization onset,
peak and conclusion temperatures, compared to the other cultivars. Differences
between the potatoes in the other properties measured did not align with the GI
ranking. Thermal analysis and starch pasting properties may be useful indicators
for preliminary identification of potato cultivars that are digested slowly and
have a lower GI.
PMID- 25124365
TI - How immigrants adapt their smoking behaviour: comparative analysis among Turkish
immigrants in Germany and the Netherlands.
AB - BACKGROUND: Smoking behaviour among immigrants is assumed to converge to that of
the host country's majority population with increasing duration of stay. We
compared smoking prevalence among Turkish immigrants residing in two different
countries (Germany (DE)/the Netherlands (NL)) between and within countries by
time spent in Turkey and DE/NL. METHODS: The German 2009 micro-census and the
Dutch POLS database (national survey, 1997-2004) were analysed. An interaction
variable with dichotomised length of stay (LOS) in Turkey (age: 0-17; 18+) and
categorised LOS in the host country (immigration year: 1979 and earlier, 1980
1999, 2000-2009; the latter only for Germany) was generated. Age standardised
smoking prevalences and sex-specific logistic regression models were calculated.
RESULTS: 6,517 Turkish participants were identified in Germany, 2,106 in the
Netherlands. Age-standardised smoking prevalences were higher among Turkish
immigrants in the Netherlands compared to those in Germany: 62.3% vs. 53.1%
(men/lower education); 30.6% vs. 23.0% (women/lower education). A similar trend
was observed for the majority population of both countries. The chance of being a
smoker was lower among Turkish men with short LOS in Turkey and middle LOS in
Germany/the Netherlands compared to those with short LOS in Turkey and long LOS
in Germany/the Netherlands (NL: OR = 0.57[95% CI = 0.36-0.89]; DE: OR = 0.73[95%
CI = 0.56-0.95]). Contrary to that, the chance of being a smoker was higher among
Turkish men with long LOS in Turkey and middle LOS in Germany/the Netherlands
compared to those with long LOS in Turkey and long LOS in Germany/the Netherlands
(NL: OR = 1.35[95% CI = 0.79-2.33]; DE: OR = 1.44[95% CI = 1.03-2.02]). The
effects for Turkish women were similar, but smaller and often non-significant.
CONCLUSION: Turkish immigrants adapt their smoking behaviour towards that of the
Dutch/German majority population with increasing duration of stay. This was
particularly obvious among those who left Turkey before the age of 18 years - a
group that needs tailored interventions to prevent further increases in smoking.
Those who left Turkey as adults and spent a short time in the host countries show
'imported' smoking patterns. A limitation of this study is the use of cross
sectional data: a cohort effect cannot be ruled out. Our findings have to be
confirmed with longitudinal data.
PMID- 25124368
TI - On selection for flowering time plasticity in response to density.
AB - Different genotypes often exhibit opposite plastic responses in the timing of the
onset of flowering with increasing plant density. In experimental studies,
selection for accelerated flowering is generally found. By contrast, game
theoretical studies predict that there should be selection for delayed flowering
when competition increases. Combining different optimality criteria, the
conditions under which accelerated or delayed flowering in response to density
would be selected for are analysed with a logistic growth simulation model. To
maximize seed production at the whole-stand level (simple optimization),
selection should lead to accelerated flowering at high plant density, unless very
short growing seasons select for similar onset of flowering at all densities. By
contrast, selection of relative individual fitness will lead to delayed flowering
when season length is long and/or growth rates are high. These different results
give a potential explanation for the observed differences in direction of the
plastic responses within and between species, including homeostasis, as a result
of the effect of the variation in season length on the benefits of delayed
flowering. This suggests that limited plasticity can evolve without the costs and
limits that are currently thought to constrain the evolution of plasticity.
PMID- 25124367
TI - Improvement of arterial oxygenation in free-ranging moose (Alces alces)
immobilized with etorphine-acepromazine-xylazine.
AB - BACKGROUND: The effect of intranasal oxygen and/or early reversal of xylazine
with atipamezole on arterial oxygenation in free-ranging moose (Alces alces)
immobilized with etorphine-acepromazine-xylazine with a cross-sectional clinical
study on 33 adult moose was evaluated. RESULTS: Before treatment the mean+/-SD
(range) partial pressure of arterial oxygen (PaO2) was 62+/-17 (26-99) mmHg.
Twenty-six animals had a PaO2<80 mmHg. Ten had a PaO2 of 40-60 mmHg and three
animals had a PaO2<40 mmHg. Intranasal oxygen and intravenous administration of
atipamezole significantly increased the mean PaO2, as did the combination of the
two. In contrast, atipamezole administered intramuscularly at the evaluated dose
had no significant effect on arterial oxygenation. CONCLUSIONS: This study shows
that intranasal oxygen effectively improved arterial oxygenation in immobilized
moose, and that early intravenous reversal of the sedative component, in this
case xylazine, in an opioid-based immobilization drug-protocol significantly
improves arterial oxygenation.
PMID- 25124369
TI - Limitations of beta-lactam therapy for infections caused by susceptible Gram
positive bacteria.
AB - Penicillin and related beta-lactam agents have been the most widely used and most
important antimicrobials in medical history, and remain the recommended therapy
for many infectious diseases 85 years after the discovery of penicillin by
Alexander Fleming. Yet the efficacy of these agents has been undermined by two
factors - the emergence of clinically significant resistance to the antimicrobial
activity of these agents, and clinical situations in which these drugs may be
suboptimal (even though the bacterial pathogens are not "resistant" to the
drugs). Observations in experimental infection models in animals (group A
streptococcal myositis, pneumococcal meningitis and pneumonia, group B
streptococcal sepsis) and in some cases clinical studies suggest that monotherapy
with beta-lactam antibiotics may be inferior to treatment with other types of
antibiotics, alone or in combination with beta-lactams - even in situations where
the bacterial pathogens remain fully "susceptible" to beta-lactams in vitro.
PMID- 25124371
TI - Monocytes and Parkinson's disease: invaders from outside?
PMID- 25124372
TI - Reengagement of high-need individuals with serious mental illness after
discontinuation of services.
AB - OBJECTIVE: The study determined rates of reengagement in services for individuals
with serious mental illness who had discontinued services. METHODS: As part of a
quality assurance program in New York City involving continuous review of
Medicaid claims and other administrative data, clinician care monitors identified
2,834 individuals with serious mental illness who were apparently in need of care
but disengaged from services. The care monitors reviewed monthly updates of
Medicaid claims, encouraged outreach from providers who had previously worked
with identified individuals, and determined whether individuals had reengaged in
services. RESULTS: Reengagement rates over a 12-month follow-up period were low,
particularly for individuals who had been incarcerated or for whom no service
provider was available to provide outreach. CONCLUSIONS: Subgroups of disengaged
individuals with serious mental illness have different rates of reengagement.
Active outreach by providers might benefit some, but such targeting is
inefficient when the individual cannot be located.
PMID- 25124373
TI - Combined use of NGF/BDNF/bFGF promotes proliferation and differentiation of
neural stem cells in vitro.
AB - Neurotrophic factors can promote the proliferation and differentiation of neural
stem cells (NSCs). Here we report that the possibility of using bFGF in
combination with BDNF and NGF to promote proliferation and differentiation of
NSCs in vitro. C57BL/6 mouse NSCs were cultured, passaged and stained by
immunofluorescence for nestin and GFP. According to different neurotrophic
factors added to NSCs, seven experiment groups (NGF, BDNF, bFGF, bFGF+NGF,
bFGF+BDNF, NGF+BDNF and NGF+BDNF+bFGF) and a blank control group were
established. One week after induction and differentiation, results showed that
there was significant difference in the percentage of NSCs differentiating into
neurons among the experiment groups. The percentage in the multi-factor groups
was significantly higher than that in the single-factor groups (p<0.05), among
which the percentage was the highest in NGF+BDNF+bFGF group. In the two-factor
groups, the percentage in bFGF+NGF and bFGF+BDNF groups was significantly higher
than that in NGF+BDNF group (p<0.05). The NSCs growth curves showed that cells
proliferated continuously with the time of culture prolonging, but there was
significant difference between the group containing bFGF and that without bFGF.
Our results demonstrate that combined use of NGF/BDNF/bFGF significantly improved
the ability of NSCs proliferation and differentiation.
PMID- 25124374
TI - Developmental and degenerative modulation of brain-derived neurotrophic factor
transcript variants in the mouse hippocampus.
AB - Brain-derived neurotrophic factor (BDNF) is regarded as an important factor for
neurogenesis, synaptic plasticity, and neuronal network organization in brain
circuits. However, little is known about the regulation of BDNF transcript
variants in the hippocampus during postnatal development and following chemically
induced neurotoxicity. In the present study, we examined the expression of
individual BDNF transcript variants in the mouse hippocampus on postnatal day
(PD) 3, 7, 14, 21, and 56, as well as in the adult hippocampus 1, 2, 4, and 8
days after trimethyltin (TMT) treatment. During postnatal development, the
expression levels of common BDNF-coding transcripts and BDNF transcript variants
increased gradually in the hippocampus, but the temporal patterns of each exon
transcript showed significant differences. In the TMT-treated hippocampus, the
levels of common BDNF-coding transcripts and exon I, IIC, III, VII, VIII, and IXA
transcripts were significantly increased 1 day post-treatment. These observations
suggest that the differential regulation of BDNF exon transcripts may be
associated with neuronal and synaptic maturation during postnatal development,
and neuronal survival and synaptic plasticity in chemically induced
neurodegeneration.
PMID- 25124375
TI - Aminoglycoside-induced nephrotoxicity--a focus on monitoring: a review of
literature.
AB - The use of aminoglycoside (AG) antibiotics has declined over the past 15 years
primarily due to comparable potency of other antimicrobials and the
nephrotoxicity potential of AG drugs. However, resurgence in the use of AG
antimicrobials is occurring due to multidrug-resistant gram-negative nosocomial
infections. Multidrug-resistant Pseudomonas and Acinetobacter isolates as well as
extended-spectrum beta-lactamase-producing Enterobacteriaceae continue to force
clinicians to consider AG therapy for nosocomial infections in hospitalized
patients and enterococcal endocarditis. Additionally, AGs are still indicated in
the treatment of pulmonary exacerbations of cystic fibrosis. Along with the use
of AG antibiotics is the associated renal insufficiency complication. This review
discusses the mechanism for AG-induced nephrotoxicity. Patient- and drug-related
risk factors are discussed to help identify patients at increased risk. The issue
of serum-level monitoring is discussed relative to the development of
nephrotoxicity.
PMID- 25124377
TI - A Retrospective Evaluation of Response to Vitamin D Supplementation in Obese
Versus Nonobese Patients.
AB - OBJECTIVE: To evaluate the impact of body mass index (BMI) on vitamin D status
following ergocalciferol therapy. METHODS: A retrospective evaluation of patients
aged 18 years and older with a baseline serum 25(OH)D < 30 ng/mL who received
prescription ergocalciferol 50 000 IU at any dose between July 2009 and November
2011 was conducted. Patients were included if pre- and posttreatment 25(OH)D
levels were available within 3 months of therapy. RESULTS: Two hundred and
thirteen patients were included in the study with 52% having a BMI >=30 kg/m(2).
Thirty-eight different ergocalciferol regimens were prescribed, and the majority
of patients (66.2%) received a regimen consisting of 50 000 IU once weekly for
variable durations. Mean 25(OH)D levels increased from 18.8 +/- 6.6 ng/mL at
baseline to 35.0 +/- 13.8 ng/mL with 61.0% (n = 130) of patients having attained
vitamin D sufficiency, 25(OH)D >= 30 ng/mL, with their prescribed ergocalciferol
regimen. Obese patients with a BMI >=30 were less likely to attain vitamin D
sufficiency following replacement than patients with a BMI <30 kg/m(2) (52% vs
71%; P = .0161). CONCLUSION: Our study demonstrated an overall moderate response
rate to replacement therapy with ergocalciferol and considerable variability in
vitamin D replacement strategies initiated by primary care providers. Based on
our findings, elevated BMI >=30 kg/m(2) may impact the likelihood of attaining
vitamin D sufficiency with ergocalciferol.
PMID- 25124376
TI - Stress, Drugs, and Alcohol Use Among Health Care Professional Students: A Focus
on Prescription Stimulants.
AB - OBJECTIVE: To contrast the characteristics of pharmacy, medicine, and physician
assistant (PA) students regarding the prevalence of drug, alcohol, and tobacco
use and to identify risk factors associated with prescription stimulant use.
PARTICIPANTS: Five hundred eighty nine students were recruited to complete a 50
item Web-based survey. MAIN OUTCOME MEASURES: Demographics, nonmedical
prescription medication use, illicit drug and alcohol use, Diagnostic and
Statistical Manual of Mental Disorders (Fourth Edition, Text Revision; DSM-IV-TR)
psychiatric diagnoses, and perceived stress scale (PSS) scores. RESULTS: Medicine
and PA students reported greater nonmedical prescription stimulant use than
pharmacy students (10.4% vs 14.0% vs 6.1%; P < .05). Medicine and PA students
were more likely to report a history of an anxiety disorder (12.1% vs 18.6% vs
5.9%; P < .05), major depressive disorder (9.4% vs 8.1% vs 3.3%; P < .05), and
attention-deficit hyperactivity disorder (ADHD; 4.0% vs 9.3% vs 0.7%; P < .001)
than pharmacy students. PSS scores for all 3 groups (21.9-22.3) were roughly
twice as high as the general adult population. CONCLUSION: Illicit drug and
prescription stimulant use, psychiatric disorders, and elevated stress levels are
prevalent among health care professional students. Health care professional
programs may wish to use this information to better understand their student
population which may lead to a reassessment of student resources and
awareness/prevention programs.
PMID- 25124378
TI - Angioedema related to Angiotensin inhibitors.
AB - Angiotensin inhibitors have been extensively evaluated in clinical trials and
have demonstrated significant reductions in morbidity and mortality following
myocardial infarction and stroke, as well as in patients with heart failure or
who are at risk of cardiovascular disease. Further, both angiotensin-converting
enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are frequently
prescribed for the treatment of hypertension and to preserve renal function in
patients with diabetes mellitus and chronic kidney disease. Angioedema is a
known, but rare, adverse effect of ACEIs and ARBs. Therefore, it is important for
clinicians to have a thorough understanding of risks and benefits of prescribing
these medications, particularly in patients with a history of angioedema. This
review describes the literature evaluating the incidence and cross-reactivity of
angioedema with ACEIs and ARBs in order to provide guidance for clinical decision
making.
PMID- 25124380
TI - Beta-lactam hypersensitivity and cross-reactivity.
AB - Penicillin is the most frequently reported cause of drug allergy, and cross
reactivity of penicillins with other beta-lactam antibiotics is an area of
debate. This review evaluates the available data on immunoglobulin E-mediated
penicillin hypersensitivity and cross-reactivity with cephalosporin, carbapenem,
and monobactam antibiotics. A MEDLINE search was conducted from 1950 to October
2013, and selected references from review articles were also evaluated. There is
a wide variety in reported incidences of cross-reactivity between penicillins and
cephalosporins or carbapenems, with early retrospective studies suggesting up to
41.7% and 47.4% cross-reactivity, respectively. Conversely, the use of monobactam
antibiotics is frequently employed in the case of a penicillin allergy, as
prescribers believe that there is no cross-reactivity between the 2 drug classes.
More recent prospective studies suggest that the rates of cross-reactivity with
cephalosporins and carbapenems are <5% and <1%, respectively. Similarities in
penicillin and cephalosporin side chains may play a role in cross-reactivity
between these classes. Cross-reactivity with monobactams is essentially
negligible; however, there are some clinical data to support an interaction
between ceftazidime and aztreonam, due to the similarity of their side chains.
The data reviewed suggest that avoidance of other beta-lactams in patients with
type 1 hypersensitivity to penicillins should be reconsidered.
PMID- 25124379
TI - Nonchemotherapy drug-induced neutropenia and agranulocytosis: could medications
be the culprit?
AB - Drug-induced agranulocytosis is a severe complication that has been implicated
with most classes of medications. Medications such as clozapine, trimethoprim
sulfamethoxazole and methimazole have been more commonly associated with
agranulocytosis than other agents. Although the pathogenesis isn't fully
elucidated, it appears to be two-fold with a direct toxicity to the myeloid cell
line and immune-mediated destruction. Patients may be asymptomatic at the time
neutropenia is discovered or may present with more severe complications such as
sepsis. In approximately 5% of cases drug-induced agranulocytosis may be fatal.
Management of drug-induced agranulocytosis includes the immediate discontinuation
of the offending medication, initiation of broad-spectrum antibiotics and
consideration of the use of granulocyte colony-stimulating factors in high-risk
patients.
PMID- 25124381
TI - Links between patterns of racial socialization and discrimination experiences and
psychological adjustment: a cluster analysis.
AB - This study used a person-oriented analytic approach to identify meaningful
patterns of barriers-focused racial socialization and perceived racial
discrimination experiences in a sample of 295 late adolescents. Using cluster
analysis, three distinct groups were identified: Low Barrier Socialization-Low
Discrimination, High Barrier Socialization-Low Discrimination, and High Barrier
Socialization-High Discrimination clusters. These groups were substantively
unique in terms of the frequency of racial socialization messages about bias
preparation and out-group mistrust its members received and their actual
perceived discrimination experiences. Further, individuals in the High Barrier
Socialization-High Discrimination cluster reported significantly higher
depressive symptoms than those in the Low Barrier Socialization-Low
Discrimination and High Barrier Socialization-Low Discrimination clusters.
However, no differences in adjustment were observed between the Low Barrier
Socialization-Low Discrimination and High Barrier Socialization-Low
Discrimination clusters. Overall, the findings highlight important individual
differences in how young people of color experience their race and how these
differences have significant implications on psychological adjustment.
PMID- 25124382
TI - Methylenetetrahydrofolate reductase C667T polymorphism is associated with
increased risk of coronary artery disease in a Chinese population.
AB - Coronary artery disease (CAD) is a complex disease resulting from a combination
of environmental and genetic factors. We hypothesized that polymorphisms in
methylenetetrahydrofolate reductase (MTHFR) rs1801133 C/T, matrix
metalloproteinases (MMPs)-2, tumour necrosis factor (TNF)-alpha, macrophage
migration inhibitory factor (MIF) rs755622 G/C and cyclin D1 (CCND1) rs678653 G/C
contribute to CAD susceptibility. We examined the association between the five
polymorphisms and the risk of CAD in a Chinese population of 435 CAD patients and
480 controls. Genotyping was performed using matrix-assisted laser desorption
ionization/time-of-flight mass spectrometry (MALDI/TOF MS). When the MTHFR
rs1801133 CC homozygote genotype was used as the reference group, the TT or CT/TT
genotypes were associated with a significantly increased risk for CAD. The CT
heterozygote genotype was not associated with the risk for CAD. Logistic
regression analyses revealed that MMP-2 rs243865 C/T, TNF-alpha rs1800629 A/G,
MIF rs755622 G/C and CCND1 rs678653 G/C polymorphisms were not associated with
the risk of CAD. These findings suggest that the MTHFR rs1801133 C/T polymorphism
is associated with CAD development. Future larger studies with other ethnic
populations are required to confirm current findings.
PMID- 25124383
TI - Protective effect of chemically modified SOD on lipid peroxidation and
antioxidant status in diabetic rats.
AB - Reactive oxygen species mediated oxidative stress play an important role on the
injury of tissue damage and increased attention has been focused on the role of
free radicals in diabetes mellitus (DM). In the present study firstly superoxide
dismutase (SOD) enzyme was chemically modified with two different polymer and
physicochemical properties of these conjugates clearly analyzed. Then, the
stability of carboxymethylcellulose-SOD (CMC-SOD) and poly methyl vinyl ether-co
maleic anhydride-SOD (PMVE/MA-SOD) conjugates was investigated against
temperature and externally added H2O2. Moreover, we investigated the effect of
chemically modified SOD enzyme on lipid peroxidation and antioxidant status in
streptozotocin (STZ)-induced diabetic rats. PMVE/MA-SOD conjugate treatment
significantly reduced MDA level compared with the control groups, native and CMC
SOD conjugate treated groups in brain, kidney and liver tissue. GSH and SOD
enzyme activity in diabetic groups was significantly increased by treatment of
CMC-SOD and PMVE/MA-SOD conjugates. The protective effects on degenerative
changes in diabetic rats were also further confirmed by histopathological
examination. This study provides the preventative activity of SOD-polymer
conjugates against complication of oxidative stress in experimentally induced
diabetic rats. These results suggest that chemically modified SOD is effective on
the oxidative stress-associated disease and offer a therapeutic advantage in
clinical use.
PMID- 25124384
TI - Template-free synthesis and mechanistic study of porous three-dimensional
hierarchical uranium-containing and uranium oxide microspheres.
AB - A novel type of uranium-containing microspheres with an urchin-like hierarchical
nano/microstructure has been successfully synthesized by a facile template-free
hydrothermal method with uranyl nitrate hexahydrate, urea, and glycerol as the
uranium source, precipitating agent, and shape-controlling agent, respectively.
The as-synthesized microspheres were usually a few micrometers in size and porous
inside, and their shells were composed of nanoscale rod-shaped crystals. The
growth mechanism of the hydrothermal reaction was studied, revealing that
temperature, ratios of reactants, solution pH, and reaction time were all
critical for the growth. The mechanism study also revealed that an intermediate
compound of 3 UO3 ?NH3 ?5 H2 O was first formed and then gradually converted into
the final hydrothermal product. These uranium-containing microspheres were
excellent precursors to synthesize porous uranium oxide microspheres. With a
suitable calcination temperature, very uniform microspheres of uranium oxides
(UO2+x , U3 O8 , and UO3 ) were successfully synthesized.
PMID- 25124386
TI - The mobile phone compatible burns dressing.
PMID- 25124385
TI - Withdrawal of antiepileptic drugs in glioma patients after long-term seizure
freedom: design of a prospective observational study.
AB - BACKGROUND: Epilepsy is common in patients with a glioma. Antiepileptic drugs
(AEDs) are the mainstay of epilepsy treatment, but may cause side effects and may
negatively impact neurocognitive functioning and quality of life. Besides
antiepileptic drugs, anti-tumour treatment, which currently consists of surgery,
radiotherapy and/or chemotherapy, may contribute to seizure control as well. In
glioma patients with seizure freedom after anti-tumour therapy the question
emerges whether AEDs should be continued, particularly in the case where anti
tumour treatment has been successful. We propose to explore the possibility of
AED withdrawal in glioma patients with long-term seizure freedom after anti
tumour therapy and without signs of tumour progression. METHODS/DESIGN: We
initiate a prospective, observational study exploring the decision-making process
on the withdrawal or continuation of AEDs in low-grade and anaplastic glioma
patients with stable disease and prolonged seizure freedom after anti-tumour
treatment, and the effects of AED withdrawal or continuation on seizure freedom.
We recruit participants through the outpatient clinics of three tertiary referral
centers for brain tumour patients in The Netherlands. The patient and the
treating physician make a shared decision to either withdraw or continue AED
treatment. Over a one-year period, we aim to include 100 glioma patients. We
expect approximately half of the participants to be willing to withdraw AEDs. The
primary outcome measures are: 1) the outcome of the shared-decision making on AED
withdrawal or continuation, and decision related arguments, and 2) seizure
freedom at 12 months and 24 months of follow-up. We will also evaluate seizure
type and frequency in case of seizure recurrence, as well as neurological
symptoms, adverse effects related to AED treatment or withdrawal, other anti
tumour treatments and tumour progression. DISCUSSION: This study addresses two
issues that are currently unexplored. First, it will explore the willingness to
withdraw AEDs in glioma patients, and second, it will assess the risk of seizure
recurrence in case AEDs are withdrawn in this specific patient population. This
study aims to contribute to a more tailored AED treatment, and prevent
unnecessary and potentially harmful use of AEDs in glioma patients.
PMID- 25124387
TI - Reconstitution of cytoskeletal protein assemblies for large-scale membrane
transformation.
AB - Membranes determine two-dimensional and three-dimensional biochemical reaction
spaces in living systems. Defining size and shape of surfaces and volumes
encompassed by membrane is of key importance for cellular metabolism and
homeostasis, and the maintenance and controlled transformation of membrane shapes
are coordinated by a large number of different protein assemblies. The
orchestration of spatial elements over distances orders of magnitudes larger than
protein molecules, as required for cell division, is a particularly challenging
task, requiring large-scale ordered protein filaments and networks. The structure
and function of these networks, particularly of cytoskeletal elements, have been
characterized extensively in cells and reconstituted systems. However, their co
reconstitution with membranes from the bottom-up under defined conditions, to
elucidate their mode of action in detail, is still a relatively new field of
research. In this short review, we discuss recent approaches and achievements
with regard to the study of cytoskeletal protein assemblies on model membranes,
with specific focus on contractile elements as those based on the bacterial
division FtsZ protein and eukaryotic actomyosin structures.
PMID- 25124388
TI - Combining quantitative trait loci analysis with physiological models to predict
genotype-specific transpiration rates.
AB - Transpiration is controlled by evaporative demand and stomatal conductance (gs ),
and there can be substantial genetic variation in gs . A key parameter in
empirical models of transpiration is minimum stomatal conductance (g0 ), a trait
that can be measured and has a large effect on gs and transpiration. In
Arabidopsis thaliana, g0 exhibits both environmental and genetic variation, and
quantitative trait loci (QTL) have been mapped. We used this information to
create a genetically parameterized empirical model to predict transpiration of
genotypes. For the parental lines, this worked well. However, in a recombinant
inbred population, the predictions proved less accurate. When based only upon
their genotype at a single g0 QTL, genotypes were less distinct than our model
predicted. Follow-up experiments indicated that both genotype by environment
interaction and a polygenic inheritance complicate the application of genetic
effects into physiological models. The use of ecophysiological or 'crop' models
for predicting transpiration of novel genetic lines will benefit from
incorporating further knowledge of the genetic control and degree of independence
of core traits/parameters underlying gs variation.
PMID- 25124389
TI - Clear cell urothelial carcinoma of the urinary bladder: a case report and review
of the literature.
AB - INTRODUCTION: The occurrence of clear cell tumors in the bladder is not uncommon.
Clear cell dysplasia is well-described and characterized by focal replacement of
transitional mucosa by cells with abundant clear cytoplasm, nuclear enlargement,
and a granular chromatin pattern. Clear cells can also be seen in clear cell
adenocarcinoma, which is rare, comprising 0.5% to 2.0% of the reported bladder
carcinomas. Other clear cell tumors found in the bladder to be considered in the
differential diagnosis are tumors of Mullerian origin and metastatic lesions,
such as renal cell carcinoma, clear cell sarcoma, and malignant melanoma. Clear
cell urothelial carcinoma is exceedingly rare, with only nine clinical cases
described in the literature. CASE PRESENTATION: We report the case of a 75-year
old Caucasian man who presented with intermittent hematuria, in whom a bladder
tumor was identified. A final histopathology examination of a cystoprostatectomy
specimen revealed a pT3b, G3 urothelial carcinoma of clear cell type (>90% clear
cells) and a prostatic adenocarcinoma of Gleason grade 3+3 (score=6). The bladder
tumor consisted of sheets of malignant cells with severe nuclear atypia and
abundant clear cytoplasm; no glandular or tubular structures were identified.
Tumor cells were periodic acid-Schiff positive and negative after diastase
treatment; additional mucicarmine and oil red O stains were negative.
Immunohistochemical stains showed the tumor cells positive for cytokeratin 7
(CK7), p63 (>80% nuclei), p53 (about 30% nuclei), vimentin, E-cadherin, cluster
of differentiation (CD10), and Ki-67 (>70% nuclei). Stains for cell adhesion
molecule 5.2 (CAM 5.2), CD117, cytokeratin 20 (CK20), human melanoma black 45
(HMB-45), paired box protein (PAX 8), placental alkaline phosphatase (PLAP),
prostate specific antigen (PSA), renal cell carcinoma (RCC), cancer antigen 25
(CA25), leukocyte common antigen (LC), S-100 protein, and uroplakin III were all
negative. CONCLUSIONS: The tumor marker profile was consistent with clear cell
type carcinoma of urothelial origin. Within the differential diagnoses, we ruled
out other possible tumor types such as urothelial carcinoma with focal clear cell
differentiation, clear cell adenocarcinoma, Mullerian tumors, and metastatic
disease.
PMID- 25124390
TI - Finite element evaluation of three methods of stable fixation of condyle base
fractures.
AB - The surgical treatment of mandibular condyle fractures currently offers several
possibilities for stable internal fixation. In this study, a finite element model
evaluation was performed of three different methods for osteosynthesis of low
subcondylar fractures: (1) two four-hole straight plates, (2) one seven-hole
lambda plate, and (3) one four-hole trapezoidal plate. The finite element model
evaluation considered a load applied to the first molar on the contralateral side
to the fracture. Results showed that, although the three methods are capable of
withstanding functional loading, the lambda plate displayed a more homogeneous
stress distribution for both osteosynthesis material and bone and may be a better
method when single-plate fixation is the option.
PMID- 25124391
TI - Palatal osteotomy with vestibuloplasty for the treatment of severe maxillary
atrophy: a new twist on an old technique.
AB - Nowadays, upper denture instability secondary to severe maxillary atrophy is
treated, in most cases, with dental implants. However, a significant number of
patients cannot afford this procedure. Palatal bone deepening through a U-shaped
osteotomy has been described previously. The procedure increases retention by
improving the suction effect of the palate and prevents anteroposterior and
lateral movement of the denture. By combining this procedure with a secondary
epithelialization vestibuloplasty, the labial aspect of the ridge is also
extended and it does not require a skin graft. This article describes a
modification of the palatal vault osteotomy through the presentation of a case.
PMID- 25124392
TI - UDP-galactose 4'-epimerase from the liver fluke, Fasciola hepatica: biochemical
characterization of the enzyme and identification of inhibitors.
AB - Leloir pathway enzyme uridine diphosphate (UDP)-galactose 4'-epimerase from the
common liver fluke Fasciola hepatica (FhGALE) was identified and characterized.
The enzyme can be expressed in, and purified from, Escherichia coli. The
recombinant enzyme is active: the K(m) (470 MUM) is higher than the corresponding
human enzyme (HsGALE), whereas the k(cat) (2.3 s(-1)) is substantially lower.
FhGALE binds NAD(+) and has shown to be dimeric by analytical gel filtration.
Like the human and yeast GALEs, FhGALE is stabilized by the substrate UDP
galactose. Molecular modelling predicted that FhGALE adopts a similar overall
fold to HsGALE and that tyrosine 155 is likely to be the catalytically critical
residue in the active site. In silico screening of the National Cancer Institute
Developmental Therapeutics Program library identified 40 potential inhibitors of
FhGALE which were tested in vitro. Of these, 6 showed concentration-dependent
inhibition of FhGALE, some with nanomolar IC50 values. Two inhibitors (5
fluoroorotate and N-[(benzyloxy)carbonyl]leucyltryptophan) demonstrated
selectivity for FhGALE over HsGALE. These compounds also thermally destabilized
FhGALE in a concentration-dependent manner. Interestingly, the selectivity of 5
fluoroorotate was not shown by orotic acid, which differs in structure by 1
fluorine atom. These results demonstrate that, despite the structural and
biochemical similarities of FhGALE and HsGALE, it is possible to discover
compounds which preferentially inhibit FhGALE.
PMID- 25124394
TI - Multi-stakeholder collaboration in the redesign of family-centered rounds
process.
AB - A human factors approach to healthcare system redesign emphasizes the involvement
of multiple healthcare stakeholders (e.g., patients and families, healthcare
providers) in the redesign process. This study explores the experience of
multiple stakeholders with collaboration in a healthcare system redesign project.
Interviews were conducted with ten stakeholder representatives who participated
in the redesign of the family-centered rounds process in a pediatric hospital.
Qualitative interview data were analyzed using a phenomenological approach. A
model of collaborative healthcare system redesign was developed, which defined
four phases (i.e., setup of the redesign team, preparation for meetings,
collaboration in meetings, follow-up after meetings) and two outcomes (i.e., team
outcomes, redesign outcomes) of the collaborative process. Challenges to multi
stakeholder collaboration in healthcare system redesign, such as need to
represent all relevant stakeholders, scheduling of meetings and managing
different perspectives, were identified.
PMID- 25124395
TI - Supraglottitis due to group B streptococcus in an adult with IgG4 and C2
deficiency: a case report and review of the literature.
AB - Acute supraglottitis is a medical emergency as it can rapidly lead to airway
compromise. With routine pediatric immunization for Hemophilus influenzae
serotype b, supraglottitis is now more prevalent in adults, with a shift in the
causative organisms and a change in the natural history of this disease. Here, we
present a case of supraglottitis due to group B streptococcus that occurred in an
adult with previously undetected immunoglobulin 4 (IgG4) and complement protein
C2 deficiency.
PMID- 25124396
TI - Effects of data sampling on graphical depictions of learning.
AB - Continuous and discontinuous data-collection methods were compared in the context
of discrete-trial programming. Archival data sets were analyzed using trial
sampling (1st 5 trials, 1st 3 trials, and 1st trial only) and session sampling
(every other session, every 3rd session, and every 5th session). Results showed
that trial sampling systematically underestimated the number of sessions and days
to mastery and overestimated the number of sessions and days to the 1st
independent response. Session sampling systematically overestimated both sessions
and days to mastery and sessions and days to the 1st independent response. A time
savings analysis was included to evaluate empirically how much time would be
saved by using each sampling method. Results suggested that data sampling would
produce relatively minimal time savings.
PMID- 25124393
TI - Influence of noninjecting and injecting drug use on mortality, retention in the
cohort, and antiretroviral therapy, in participants in the Swiss HIV Cohort
Study.
AB - OBJECTIVES: We studied the influence of noninjecting and injecting drug use on
mortality, dropout rate, and the course of antiretroviral therapy (ART), in the
Swiss HIV Cohort Study (SHCS). METHODS: Cohort participants, registered prior to
April 2007 and with at least one drug use questionnaire completed until May 2013,
were categorized according to their self-reported drug use behaviour. The
probabilities of death and dropout were separately analysed using multivariable
competing risks proportional hazards regression models with mutual correction for
the other endpoint. Furthermore, we describe the influence of drug use on the
course of ART. RESULTS: A total of 6529 participants (including 31% women) were
followed during 31 215 person-years; 5.1% participants died; 10.5% were lost to
follow-up. Among persons with homosexual or heterosexual HIV transmission,
noninjecting drug use was associated with higher all-cause mortality [subhazard
rate (SHR) 1.73; 95% confidence interval (CI) 1.07-2.83], compared with no drug
use. Also, mortality was increased among former injecting drug users (IDUs) who
reported noninjecting drug use (SHR 2.34; 95% CI 1.49-3.69). Noninjecting drug
use was associated with higher dropout rates. The mean proportion of time with
suppressed viral replication was 82.2% in all participants, irrespective of ART
status, and 91.2% in those on ART. Drug use lowered adherence, and increased
rates of ART change and ART interruptions. Virological failure on ART was more
frequent in participants who reported concomitant drug injections while on opiate
substitution, and in current IDUs, but not among noninjecting drug users.
CONCLUSIONS: Noninjecting drug use and injecting drug use are modifiable risks
for death, and they lower retention in a cohort and complicate ART.
PMID- 25124398
TI - Bipolar stacked quasi-all-solid-state lithium secondary batteries with output
cell potentials of over 6 V.
AB - Designing a lithium ion battery (LIB) with a three-dimensional device structure
is crucial for increasing the practical energy storage density by avoiding
unnecessary supporting parts of the cell modules. Here, we describe the superior
secondary battery performance of the bulk all-solid-state LIB cell and a
multilayered stacked bipolar cell with doubled cell potential of 6.5 V, for the
first time. The bipolar-type solid LIB cell runs its charge/discharge cycle over
200 times in a range of 0.1-1.0 C with negligible capacity decrease despite their
doubled output cell potentials. This extremely high performance of the bipolar
cell is a result of the superior battery performance of the single cell; the bulk
all-solid-state cell has a charge/discharge cycle capability of over 1500
although metallic lithium and LiFePO4 are employed as anodes and cathodes,
respectively. The use of a quasi-solid electrolyte consisting of ionic liquid and
Al2O3 nanoparticles is considered to be responsible for the high ionic
conductivity and electrochemical stability at the interface between the
electrodes and the electrolyte. This paper presents the effective applications of
SiO2, Al2O3, and CeO2 nanoparticles and various Li(+) conducting ionic liquids
for the quasi-solid electrolytes and reports the best ever known cycle
performances. Moreover, the results of this study show that the bipolar stacked
three-dimensional device structure would be a smart choice for future LIBs with
higher cell energy density and output potential. In addition, our report presents
the advantages of adopting a three-dimensional cell design based on the solid
state electrolytes, which is of particular interest in energy-device engineering
for mobile applications.
PMID- 25124399
TI - Misfolding of luciferase at the single-molecule level.
AB - The folding of complex proteins can be dramatically affected by misfolding
transitions. Directly observing misfolding and distinguishing it from aggregation
is challenging. Experiments with optical tweezers revealed transitions between
the folded states of a single protein in the absence of mechanical tension.
Nonfolded chains of the multidomain protein luciferase folded within seconds to
different partially folded states, one of which was stable over several minutes
and was more resistant to forced unfolding than other partially folded states.
Luciferase monomers can thus adopt a stable misfolded state and can do so without
interacting with aggregation partners. This result supports the notion that
luciferase misfolding is the cause of the low refolding yields and aggregation
observed with this protein. This approach could be used to study misfolding
transitions in other large proteins, as well as the factors that affect
misfolding.
PMID- 25124397
TI - Use of a murine embryonic stem cell line that is sensitive to high glucose
environment to model neural tube development in diabetic pregnancy.
AB - BACKGROUND: Neural tube defects (NTDs) are significantly increased by maternal
diabetes. Embryonic stem cells (ESC) that can differentiate into neuroepithelium
and can sense supraphysiological glucose concentrations would be very valuable to
simulate the effects of maternal diabetes on molecular and cellular processes
during neural tube formation. METHODS: LG-ESC, a recently established ESC line
that expresses the glucose transporter, Scl2a2, and is sensitive to elevated
glucose concentrations, were grown for up to 8 days in a three-dimensional
culture to form neural cysts. We tested whether high glucose media inhibits
expression of Pax3, a gene that is required for neural tube closure and whose
expression is inhibited in embryos of diabetic mice, and inhibits formation of
neural cysts. RESULTS: Pax3 expression was detected after 4 days of culture and
increased with time. Pax3 expression was inhibited by high glucose media, but not
if cells had been cultured in low glucose media for the first 4 days of culture.
Pax7, which is also expressed in dorsal neural tube, was not detected. Pax6,
which is expressed in the ventral neural tube, was detected only after 8 days of
culture, but was not inhibited by high glucose. High glucose media did not
inhibit formation of neural cysts. CONCLUSION: LG-ESC can be used as a model of
embryonic exposure to a diabetic environment during neural tube development.
While high glucose exposure inhibits expression of a gene required for neural
tube closure, it may not inhibit all of the processes involved in formation of a
neural tube-like structure.
PMID- 25124400
TI - Predicting the conservation status of data-deficient species.
AB - There is little appreciation of the level of extinction risk faced by one-sixth
of the over 65,000 species assessed by the International Union for Conservation
of Nature. Determining the status of these data-deficient (DD) species is
essential to developing an accurate picture of global biodiversity and
identifying potentially threatened DD species. To address this knowledge gap, we
used predictive models incorporating species' life history, geography, and threat
information to predict the conservation status of DD terrestrial mammals. We
constructed the models with 7 machine learning (ML) tools trained on species of
known status. The resultant models showed very high species classification
accuracy (up to 92%) and ability to correctly identify centers of threatened
species richness. Applying the best model to DD species, we predicted 313 of 493
DD species (64%) to be at risk of extinction, which increases the estimated
proportion of threatened terrestrial mammals from 22% to 27%. Regions predicted
to contain large numbers of threatened DD species are already conservation
priorities, but species in these areas show considerably higher levels of risk
than previously recognized. We conclude that unless directly targeted for
monitoring, species classified as DD are likely to go extinct without notice.
Taking into account information on DD species may therefore help alleviate data
gaps in biodiversity indicators and conserve poorly known biodiversity.
PMID- 25124402
TI - Science for lasting peace.
PMID- 25124401
TI - The interrelationship between anti-Mullerian hormone, ovarian follicular
populations and age in mares.
AB - REASONS FOR PERFORMING STUDY: Anti-Mullerian hormone (AMH) is a granulosa-cell
derived glycoprotein, which plays an important inhibitory role during
folliculogenesis. Concentrations of AMH are highly correlated with antral
follicle counts (AFCs) in other species, which in turn are related to follicular
reserve. Relatively little is known about AMH and AFC in the mare. OBJECTIVES: To
determine plasma AMH concentrations and AFCs in mares of different ages, to
measure the repeatability of AMH concentrations and AFCs within and across
oestrous cycles and to assess the relationship between plasma AMH concentrations
and AFCs with regard to mare age and follicle size. STUDY DESIGN: An
observational study examining the relationship between AMH, AFC and age in 45
mares. METHODS: Young (3-8 years), middle-aged (9-18 years) and old mares (19-27
years) were examined by transrectal ultrasonography over 2 or 3 oestrous cycles.
Plasma AMH concentrations and AFCs were determined, and antral follicles were
classified by size into different groups. RESULTS: Plasma AMH concentrations
varied widely between mares within similar age groups. Antral follicle counts
were significantly lower in old mares than in young and middle-aged mares, and
AMH concentrations were significantly lower in old than in middle-aged mares. A
positive relationship was detected between AFC and AMH, and this relationship
varied by mare age with a strong correlation in older mares (rho = 0.86;
P<0.0001), a moderate correlation in middle-aged mares (rho = 0.60; P = 0.01) and
no correlation in young mares (rho = 0.40, P<0.4). The AMH concentrations were
significantly related to the number of antral follicles between 6 and 20 mm in
diameter, and the repeatability of AFCs and AMH concentrations was high within
and between oestrous cycles. CONCLUSIONS: Our findings indicate that the
relationship between AMH and AFC varies across age groups, and concentrations of
AMH might be a better reflection of reproductive age than calendar age.
PMID- 25124405
TI - Nuclear weapons. Firing of Los Alamos researcher draws criticism.
PMID- 25124404
TI - Infectious diseases. Debate erupts on 'repurposed' drugs for Ebola.
PMID- 25124406
TI - Earth science. A boom in boomless seismology.
PMID- 25124407
TI - The rising toll.
PMID- 25124408
TI - Civilian casualties in Afghanistan.
PMID- 25124409
TI - Mother of all lodes.
PMID- 25124410
TI - Information technology. Technology's limited role in resolving debates over
digital surveillance.
PMID- 25124411
TI - Medicine. Letting go of mucus.
PMID- 25124412
TI - Chemistry. Self-assembled RNA nanostructures.
PMID- 25124414
TI - Water treatment. Replace contamination, not the pipes.
PMID- 25124413
TI - Epigenetics. You are what you eat, but what about your DNA?
PMID- 25124415
TI - Biochemistry. One step closer to O2.
PMID- 25124416
TI - HIV cover ill-advised.
PMID- 25124417
TI - HIV cover ill-advised--response.
PMID- 25124418
TI - Climate change: time to navigate.
PMID- 25124419
TI - Fossil fuels' future.
PMID- 25124420
TI - Sharing ideas too soon.
PMID- 25124421
TI - Outside the Tower. Kids' questions transcend conflict.
PMID- 25124422
TI - Parenting. A legacy that transcends genes. Introduction.
PMID- 25124423
TI - Unsettled questions trail IVF's success.
PMID- 25124424
TI - Nature's first functional food.
PMID- 25124425
TI - The taste of things to come.
PMID- 25124426
TI - An experiment in zero parenting.
PMID- 25124427
TI - Maternal mental illness.
PMID- 25124428
TI - Parenting from before conception.
AB - At fertilization, the gametes endow the embryo with a genomic blueprint, the
integrity of which is affected by the age and environmental exposures of both
parents. Recent studies reveal that parental history and experiences also exert
effects through epigenomic information not contained in the DNA sequence,
including variations in sperm and oocyte cytosine methylation and chromatin
patterning, noncoding RNAs, and mitochondria. Transgenerational epigenetic
effects interact with conditions at conception to program the developmental
trajectory of the embryo and fetus, ultimately affecting the lifetime health of
the child. These insights compel us to revise generally held notions to
accommodate the prospect that biological parenting commences well before birth,
even prior to conception.
PMID- 25124429
TI - Preterm labor: one syndrome, many causes.
AB - Preterm birth is associated with 5 to 18% of pregnancies and is a leading cause
of infant morbidity and mortality. Spontaneous preterm labor, a syndrome caused
by multiple pathologic processes, leads to 70% of preterm births. The prevention
and the treatment of preterm labor have been long-standing challenges. We
summarize the current understanding of the mechanisms of disease implicated in
this condition and review advances relevant to intra-amniotic infection, decidual
senescence, and breakdown of maternal-fetal tolerance. The success of progestogen
treatment to prevent preterm birth in a subset of patients at risk is a cause for
optimism. Solving the mystery of preterm labor, which compromises the health of
future generations, is a formidable scientific challenge worthy of investment.
PMID- 25124432
TI - The evolution of flexible parenting.
AB - Parenting behaviors, such as the provisioning of food by parents to offspring,
are known to be highly responsive to changes in environment. However, we
currently know little about how such flexibility affects the ways in which
parenting is adapted and evolves in response to environmental variation. This is
because few studies quantify how individuals vary in their response to changing
environments, especially social environments created by other individuals with
which parents interact. Social environmental factors differ from nonsocial
factors, such as food availability, because parents and offspring both contribute
and respond to the social environment they experience. This interdependence leads
to the coevolution of flexible behaviors involved in parenting, which could,
paradoxically, constrain the ability of individuals to rapidly adapt to changes
in their nonsocial environment.
PMID- 25124430
TI - Neural control of maternal and paternal behaviors.
AB - Parental care, including feeding and protection of young, is essential for the
survival as well as mental and physical well-being of the offspring. A large
variety of parental behaviors has been described across species and sexes,
raising fascinating questions about how animals identify the young and how brain
circuits drive and modulate parental displays in males and females. Recent
studies have begun to uncover a striking antagonistic interplay between brain
systems underlying parental care and infant-directed aggression in both males and
females, as well as a large range of intrinsic and environmentally driven neural
modulation and plasticity. Improved understanding of the neural control of
parental interactions in animals should provide novel insights into the complex
issue of human parental care in both health and disease.
PMID- 25124431
TI - The biology of mammalian parenting and its effect on offspring social
development.
AB - Parents know the transformative nature of having and caring for a child. Among
many mammals, giving birth leads from an aversion to infant stimuli to
irresistible attraction. Here, we review the biological mechanisms governing this
shift in parental motivation in mammals. Estrogen and progesterone prepare the
uterus for embryo implantation and placental development. Prolactin stimulates
milk production, whereas oxytocin initiates labor and triggers milk ejection
during nursing. These same molecules, interacting with dopamine, also activate
specific neural pathways to motivate parents to nurture, bond with, and protect
their offspring. Parenting in turn shapes the neural development of the infant
social brain. Recent work suggests that many of the principles governing parental
behavior and its effect on infant development are conserved from rodent to
humans.
PMID- 25124434
TI - Interstellar medium. Pseudo-three-dimensional maps of the diffuse interstellar
band at 862 nm.
AB - The diffuse interstellar bands (DIBs) are absorption lines observed in visual and
near-infrared spectra of stars. Understanding their origin in the interstellar
medium is one of the oldest problems in astronomical spectroscopy, as DIBs have
been known since 1922. In a completely new approach to understanding DIBs, we
combined information from nearly 500,000 stellar spectra obtained by the massive
spectroscopic survey RAVE (Radial Velocity Experiment) to produce the first
pseudo-three-dimensional map of the strength of the DIB at 8620 angstroms
covering the nearest 3 kiloparsecs from the Sun, and show that it follows our
independently constructed spatial distribution of extinction by interstellar dust
along the Galactic plane. Despite having a similar distribution in the Galactic
plane, the DIB 8620 carrier has a significantly larger vertical scale height than
the dust. Even if one DIB may not represent the general DIB population, our
observations outline the future direction of DIB research.
PMID- 25124435
TI - Robotics. Programmable self-assembly in a thousand-robot swarm.
AB - Self-assembly enables nature to build complex forms, from multicellular organisms
to complex animal structures such as flocks of birds, through the interaction of
vast numbers of limited and unreliable individuals. Creating this ability in
engineered systems poses challenges in the design of both algorithms and physical
systems that can operate at such scales. We report a system that demonstrates
programmable self-assembly of complex two-dimensional shapes with a thousand
robot swarm. This was enabled by creating autonomous robots designed to operate
in large groups and to cooperate through local interactions and by developing a
collective algorithm for shape formation that is highly robust to the variability
and error characteristic of large-scale decentralized systems. This work advances
the aim of creating artificial swarms with the capabilities of natural ones.
PMID- 25124433
TI - Interstellar dust. Evidence for interstellar origin of seven dust particles
collected by the Stardust spacecraft.
AB - Seven particles captured by the Stardust Interstellar Dust Collector and returned
to Earth for laboratory analysis have features consistent with an origin in the
contemporary interstellar dust stream. More than 50 spacecraft debris particles
were also identified. The interstellar dust candidates are readily distinguished
from debris impacts on the basis of elemental composition and/or impact
trajectory. The seven candidate interstellar particles are diverse in elemental
composition, crystal structure, and size. The presence of crystalline grains and
multiple iron-bearing phases, including sulfide, in some particles indicates that
individual interstellar particles diverge from any one representative model of
interstellar dust inferred from astronomical observations and theory.
PMID- 25124436
TI - RNA nanostructures. A single-stranded architecture for cotranscriptional folding
of RNA nanostructures.
AB - Artificial DNA and RNA structures have been used as scaffolds for a variety of
nanoscale devices. In comparison to DNA structures, RNA structures have been
limited in size, but they also have advantages: RNA can fold during transcription
and thus can be genetically encoded and expressed in cells. We introduce an
architecture for designing artificial RNA structures that fold from a single
strand, in which arrays of antiparallel RNA helices are precisely organized by
RNA tertiary motifs and a new type of crossover pattern. We constructed RNA tiles
that assemble into hexagonal lattices and demonstrated that lattices can be made
by annealing and/or cotranscriptional folding. Tiles can be scaled up to 660
nucleotides in length, reaching a size comparable to that of large natural
ribozymes.
PMID- 25124437
TI - Photosynthesis. Electronic structure of the oxygen-evolving complex in
photosystem II prior to O-O bond formation.
AB - The photosynthetic protein complex photosystem II oxidizes water to molecular
oxygen at an embedded tetramanganese-calcium cluster. Resolving the geometric and
electronic structure of this cluster in its highest metastable catalytic state
(designated S3) is a prerequisite for understanding the mechanism of O-O bond
formation. Here, multifrequency, multidimensional magnetic resonance spectroscopy
reveals that all four manganese ions of the catalyst are structurally and
electronically similar immediately before the final oxygen evolution step; they
all exhibit a 4+ formal oxidation state and octahedral local geometry. Only one
structural model derived from quantum chemical modeling is consistent with all
magnetic resonance data; its formation requires the binding of an additional
water molecule. O-O bond formation would then proceed by the coupling of two
proximal manganese-bound oxygens in the transition state of the cofactor.
PMID- 25124438
TI - Plant science. Genomic-scale exchange of mRNA between a parasitic plant and its
hosts.
AB - Movement of RNAs between cells of a single plant is well documented, but cross
species RNA transfer is largely unexplored. Cuscuta pentagona (dodder) is a
parasitic plant that forms symplastic connections with its hosts and takes up
host messenger RNAs (mRNAs). We sequenced transcriptomes of Cuscuta growing on
Arabidopsis and tomato hosts to characterize mRNA transfer between species and
found that mRNAs move in high numbers and in a bidirectional manner. The mobile
transcripts represented thousands of different genes, and nearly half the
expressed transcriptome of Arabidopsis was identified in Cuscuta. These findings
demonstrate that parasitic plants can exchange large proportions of their
transcriptomes with hosts, providing potential mechanisms for RNA-based
interactions between species and horizontal gene transfer.
PMID- 25124439
TI - Water engineering. Reducing sewer corrosion through integrated urban water
management.
AB - Sewer systems are among the most critical infrastructure assets for modern urban
societies and provide essential human health protection. Sulfide-induced concrete
sewer corrosion costs billions of dollars annually and has been identified as a
main cause of global sewer deterioration. We performed a 2-year sampling campaign
in South East Queensland (Australia), an extensive industry survey across
Australia, and a comprehensive model-based scenario analysis of the various
sources of sulfide. Aluminum sulfate addition during drinking water production
contributes substantially to the sulfate load in sewage and indirectly serves as
the primary source of sulfide. This unintended consequence of urban water
management structures could be avoided by switching to sulfate-free coagulants,
with no or only marginal additional expenses compared with the large potential
savings in sewer corrosion costs.
PMID- 25124440
TI - Place cells. Large environments reveal the statistical structure governing
hippocampal representations.
AB - The rules governing the formation of spatial maps in the hippocampus have not
been determined. We investigated the large-scale structure of place field
activity by recording hippocampal neurons in rats exploring a previously
unencountered 48-meter-long track. Single-cell and population activities were
well described by a two-parameter stochastic model. Individual neurons had their
own characteristic propensity for forming fields randomly along the track, with
some cells expressing many fields and many exhibiting few or none. Because of the
particular distribution of propensities across cells, the number of neurons with
fields scaled logarithmically with track length over a wide, ethological range.
These features constrain hippocampal memory mechanisms, may allow efficient
encoding of environments and experiences of vastly different extents and
durations, and could reflect general principles of population coding.
PMID- 25124444
TI - Outside my comfort zone.
PMID- 25124442
TI - Transdifferentiation. Sequential histone-modifying activities determine the
robustness of transdifferentiation.
AB - Natural interconversions between distinct somatic cell types have been reported
in species as diverse as jellyfish and mice. The efficiency and reproducibility
of some reprogramming events represent unexploited avenues in which to probe
mechanisms that ensure robust cell conversion. We report that a conserved
H3K27me3/me2 demethylase, JMJD-3.1, and the H3K4 methyltransferase Set1 complex
cooperate to ensure invariant transdifferentiation (Td) of postmitotic
Caenorhabditis elegans hindgut cells into motor neurons. At single-cell
resolution, robust conversion requires stepwise histone-modifying activities,
functionally partitioned into discrete phases of Td through nuclear degradation
of JMJD-3.1 and phase-specific interactions with transcription factors that have
conserved roles in cell plasticity and terminal fate selection. Our results draw
parallels between epigenetic mechanisms underlying robust Td in nature and
efficient cell reprogramming in vitro.
PMID- 25124443
TI - Synthetic biology. Programmable on-chip DNA compartments as artificial cells.
AB - The assembly of artificial cells capable of executing synthetic DNA programs has
been an important goal for basic research and biotechnology. We assembled two
dimensional DNA compartments fabricated in silicon as artificial cells capable of
metabolism, programmable protein synthesis, and communication. Metabolism is
maintained by continuous diffusion of nutrients and products through a thin
capillary, connecting protein synthesis in the DNA compartment with the
environment. We programmed protein expression cycles, autoregulated protein
levels, and a signaling expression gradient, equivalent to a morphogen, in an
array of interconnected compartments at the scale of an embryo. Gene expression
in the DNA compartment reveals a rich, dynamic system that is controlled by
geometry, offering a means for studying biological networks outside a living
cell.
PMID- 25124441
TI - Impaired mucus detachment disrupts mucociliary transport in a piglet model of
cystic fibrosis.
AB - Lung disease in people with cystic fibrosis (CF) is initiated by defective host
defense that predisposes airways to bacterial infection. Advanced CF is
characterized by a deficit in mucociliary transport (MCT), a process that traps
and propels bacteria out of the lungs, but whether this deficit occurs first or
is secondary to airway remodeling has been unclear. To assess MCT, we tracked
movement of radiodense microdisks in airways of newborn piglets with CF.
Cholinergic stimulation, which elicits mucus secretion, substantially reduced
microdisk movement. Impaired MCT was not due to periciliary liquid depletion;
rather, CF submucosal glands secreted mucus strands that remained tethered to
gland ducts. Inhibiting anion secretion in non-CF airways replicated CF
abnormalities. Thus, impaired MCT is a primary defect in CF, suggesting that
submucosal glands and tethered mucus may be targets for early CF treatment.
PMID- 25124446
TI - Serum protein profiles, circulating immune complexes and proteinuria in dogs
naturally infected with Anaplasma phagocytophilum.
AB - Alterations in serum protein profile, presence of circulating immune complexes
(CIC) and proteinuria were investigated in a large group of dogs naturally
infected with the Anaplasma phagocytophilum bacterium. Our aim was to evaluate
the presence of hypergammaglobulinaemia, CIC and proteinuria as a possible result
of an immune-mediated disease following infection by or exposure to A.
phagocytophilum. Dogs were divided into three groups - IFA positive (188 dogs
with confirmed exposure to A. phagocytophilum), PCR positive (31 dogs with
confirmed infection), and control (IFA and PCR negative) (19 dogs). Serum and
urine protein patterns were determined by electrophoresis and CIC concentrations
by absorbance nephelometry. No significant differences in hypergammaglobulinaemia
were observed between the different groups, as shown by the presence of acute
phase proteins alpha2 and beta1-2 globulins. CIC concentrations in the IFA and
PCR positive groups were, on average, higher than in controls by 151.3MUg/ml,
though the differences were not significant. The proportion of dogs with
proteinuria did not differ significantly between groups. Our results confirm the
assumption that anaplasmosis in dogs is most probably a disease with an acute
course, with a good prognosis under the right treatment.
PMID- 25124447
TI - Molecular detection and genotyping of Aphanomyces astaci directly from preserved
crayfish samples uncovers the Norwegian crayfish plague disease history.
AB - Aphanomyces astaci causes crayfish plague in European freshwater crayfish, but
most historical epizootics lack agent isolation and identification. Although
declared as crayfish plague outbreaks by the Norwegian Competent Authorities,
only presumptive diagnoses without agent isolation exist from Norwegian
epizootics until 2005. Molecular methods now allow both A. astaci detection and
genotype determination from preserved samples. We therefore aimed to (1)
investigate molecularly if A. astaci was involved in a selection of mass
mortality events in Norwegian noble crayfish populations from 1971 to 2004, and
(2) determine the eventually involved A. astaci genotype groups both from these
historical and also more recent mass-mortality events. DNA was extracted directly
from presumptively infected crayfish tissues, and screened by A. astaci specific
qPCR. A representative selection of positive samples was confirmed by ITS
sequencing. Finally, genotype determination was performed with microsatellite
markers that distinguish all known A. astaci genotype groups. The molecular
examination detected A. astaci in crayfish materials from all examined mass
mortality events. The first event in 1971-1974 was caused by the A. astaci
genotype group A, presumably the first genotype group that entered Europe more
than 150 years ago. All later outbreaks were caused by the A. astaci genotype
group B which was introduced to Europe by importation of signal crayfish in the
1960s. The results suggest that molecular methods can verify the involvement of
A. astaci in the vast majority of observed crayfish mass mortalities in Europe
whenever preserved materials exist. Moreover, microsatellite genotyping can
reveal at least parts of the underlying epidemiology.
PMID- 25124448
TI - Development of an APP Helpful to Manage Patients with Low Back Pain.
PMID- 25124450
TI - Evaluation of sphingomyelin, cholester, and phosphatidylcholine-based immobilized
artificial membrane liquid chromatography to predict drug penetration across the
blood-brain barrier.
AB - Over the past decades, several in vitro methods have been tested for their
ability to predict drug penetration across the blood-brain barrier. So far, in
high-performance liquid chromatography, most attention has been paid to micellar
liquid chromatography and immobilized artificial membrane (IAM) LC. IAMLC has
been described as a viable approach, since the stationary phase emulates the
lipid environment of a cell membrane. However, research in IAMLC has almost
exclusively been limited to phosphatidylcholine (PC)-based stationary phases,
even though PC is only one of the lipids present in cell membranes. In this
article, sphingomyelin and cholester stationary phases have been tested for the
first time towards their ability to predict drug penetration across the blood
brain barrier. Upon comparison with the PC stationary phase, the sphingomyelin-
and cholester-based columns depict similar predictive performance. Combining data
from the different stationary phases did not lead to improvements of the models.
PMID- 25124453
TI - Nephrotic syndrome in hand, foot and mouth disease caused by coxsackievirus A16:
a case report.
AB - Some viruses, including certain members of the enterovirus genus, have been
reported to cause nephrotic syndrome. However, no case of coxsackievirus A16
(CVA16)-related nephrotic syndrome has been reported so far. We describe a case
of CVA16-related hand, foot and mouth disease presenting with nephrotic syndrome
in a 3-year-old boy. This is the first report of CVA16-related nephrotic
syndrome.
PMID- 25124454
TI - On confirmation bias in imaging research.
PMID- 25124452
TI - The absence of exanthema is related with death and illness severity in acute
enterovirus infection.
AB - OBJECTIVE: To clarify whether exanthema is related to illness severity in acute
enterovirus infection in children. METHODS: The data of pediatric inpatients at
Zhujiang Hospital during 2009-2012 with an acute enterovirus infection were
reviewed retrospectively. Enterovirus infection was determined by real-time
reverse transcription PCR. Clinical data were summarized and compared between
cases with and without exanthema. RESULTS: A total of 780 pediatric inpatients
with an acute enterovirus infection were included in this study, of whom 83
(10.6%) presented no exanthema. The percentage of deaths in the group of patients
without exanthema was significantly higher than that in the group with exanthema
(7.2% vs. 1.1%; p = 0.002). Central nervous system involvement (41.0% vs. 30.0%;
p = 0.041), severe central nervous system (CNS) involvement (21.7% vs. 11.0%; p =
0.005), severe CNS involvement with cardiopulmonary failure (9.6% vs. 2.3%; p =
0.002), an altered level of consciousness (15.7% vs. 7.6%; p = 0.013), and
convulsions (14.4% vs. 6.3%; p = 0.007) occurred significantly more frequently in
the group without exanthema. CONCLUSIONS: A considerable proportion of children
with an acute enterovirus infection in Guangdong Province, China during 2009-2012
presented no exanthema, and the absence of exanthema was found to be related to
death and illness severity for these acute enterovirus infections. Clinicians in
China should consider enterovirus as the possible pathogen when treating children
with an acute pathogen infection without exanthema.
PMID- 25124451
TI - Absence of plastin 1 causes abnormal maintenance of hair cell stereocilia and a
moderate form of hearing loss in mice.
AB - Hearing relies on the mechanosensory inner and outer hair cells (OHCs) of the
organ of Corti, which convert mechanical deflections of their actin-rich
stereociliary bundles into electrochemical signals. Several actin-associated
proteins are essential for stereocilia formation and maintenance, and their
absence leads to deafness. One of the most abundant actin-bundling proteins of
stereocilia is plastin 1, but its function has never been directly assessed.
Here, we found that plastin 1 knock-out (Pls1 KO) mice have a moderate and
progressive form of hearing loss across all frequencies. Auditory hair cells
developed normally in Pls1 KO, but in young adult animals, the stereocilia of
inner hair cells were reduced in width and length. The stereocilia of OHCs were
comparatively less affected; however, they also showed signs of degeneration in
ageing mice. The hair bundle stiffness and the acquisition of the
electrophysiological properties of hair cells were unaffected by the absence of
plastin 1, except for a significant change in the adaptation properties, but not
the size of the mechanoelectrical transducer currents. These results show that in
contrast to other actin-bundling proteins such as espin, harmonin or Eps8,
plastin 1 is dispensable for the initial formation of stereocilia. However, the
progressive hearing loss and morphological defects of hair cells in adult Pls1 KO
mice point at a specific role for plastin 1 in the preservation of adult
stereocilia and optimal hearing. Hence, mutations in the human PLS1 gene may be
associated with relatively mild and progressive forms of hearing loss.
PMID- 25124455
TI - Refinement of the critical region in a new 7p22.1 microduplication syndrome
including craniofacial dysmorphism and speech delay.
PMID- 25124457
TI - Intimacy motivations and pre-exposure prophylaxis (PrEP) adoption intentions
among HIV-negative men who have sex with men (MSM) in romantic relationships.
AB - BACKGROUND: In the USA, men who have sex with men (MSM) in primary partnerships
are at elevated risk for human immunodeficiency virus (HIV) infection. Pre
exposure prophylaxis (PrEP), a new biomedical prevention strategy, has potential
to reduce HIV transmission. This study examined predictors of PrEP adoption
intentions among HIV-negative MSM in primary partnerships. METHODS: The sample
included HIV-negative MSM (n = 164) who participated in an ongoing cross
sectional study with an in-person interview examining PrEP adoption intentions.
RESULTS: Higher HIV risk perception, intimacy motivations for condomless sex,
recent condomless anal sex with outside partners, education, and age were each
independently associated with PrEP adoption intentions. In a multivariate model,
only age, education, and intimacy motivations for condomless sex were
significantly associated with PrEP adoption intentions. CONCLUSIONS: Intimacy
motivations may play a central role in PrEP adoption for MSM couples.
Incorporating relationship dynamics into biomedical strategies is a promising
avenue for research and intervention.
PMID- 25124456
TI - Randomized controlled trial of Qigong/Tai Chi Easy on cancer-related fatigue in
breast cancer survivors.
AB - BACKGROUND: Many breast cancer survivors experience fatigue, mood, and sleep
disturbances. PURPOSE: This study aims to compare a meditative movement practice,
Qigong/Tai Chi Easy (QG/TCE) with sham Qigong (SQG), testing effects of
meditation/breath aspects of QG/TCE on breast cancer survivors' persistent
fatigue and other symptoms. METHODS: This double-blind, randomized controlled
trial tested 12 weeks of QG/TCE versus SQG on fatigue, depression, and sleep
among 87 postmenopausal, fatigued breast cancer survivors, stages 0-III, age 40
75. RESULTS: Fatigue decreased significantly in the QG/TCE group compared to
control at post-intervention (p = 0.005) and 3 months follow-up (p = 0.024), but
not depression and sleep quality. Improvement occurred over time for both
interventions in depression and sleep quality (all p < 0.05). CONCLUSIONS: QG/TCE
showed significant improvement over time compared to SQG for fatigue, but not
depression or sleep. Both QG/TCE and SQG showed improvement for two prevalent
symptoms among breast cancer survivors, depression and sleep dysfunction.
PMID- 25124459
TI - The conservative management of renal trauma: a literature review and practical
clinical guideline from Australia and New Zealand.
AB - OBJECTIVE: To review the literature and make practical recommendations regarding
the conservative management of renal trauma. PATIENTS AND METHODS: Relevant
articles and guidelines published between 1980 and 2014 were reviewed. Graded
recommendations were constructed by a multi-disciplinary panel consisting of
urologists, radiologists, and infectious disease physicians. These
recommendations underwent formal review and debate at the Western Australian
USANZ 2013 state conference, and were presented at the USANZ 2014 annual
scientific meeting. RESULTS: The literature on the conservative management of
renal trauma is reviewed within the framework of the American Association for the
Surgery of Trauma (AAST) kidney injury severity scale. Graded recommendations are
made regarding several key topics including: imaging, inpatient management,
antibiotics, return to activity, and follow-up. Grade IV injuries and
intraoperative consults are examined separately in view of the difficulties these
groups cause in making appropriate treatment decisions. CONCLUSION: A practical
clinical guideline is provided regarding the conservative management of renal
trauma.
PMID- 25124458
TI - Microtubules provide directional information for core PCP function.
AB - Planar cell polarity (PCP) signaling controls the polarization of cells within
the plane of an epithelium. Two molecular modules composed of
Fat(Ft)/Dachsous(Ds)/Four-jointed(Fj) and a 'PCP-core' including Frizzled(Fz) and
Dishevelled(Dsh) contribute to polarization of individual cells. How polarity is
globally coordinated with tissue axes is unresolved. Consistent with previous
results, we find that the Ft/Ds/Fj-module has an effect on a MT-cytoskeleton.
Here, we provide evidence for the model that the Ft/Ds/Fj-module provides
directional information to the core-module through this MT organizing function.
We show Ft/Ds/Fj-dependent initial polarization of the apical MT-cytoskeleton
prior to global alignment of the core-module, reveal that the anchoring of apical
non-centrosomal MTs at apical junctions is polarized, observe that directional
trafficking of vesicles containing Dsh depends on Ft, and demonstrate the
feasibility of this model by mathematical simulation. Together, these results
support the hypothesis that Ft/Ds/Fj provides a signal to orient core PCP
function via MT polarization.
PMID- 25124463
TI - Assembling ellipsoidal particles at fluid interfaces using switchable dipolar
capillary interactions.
AB - How to dynamically tune an assembly of anisotropic colloidal particles adsorbed
at fluid-fluid interfaces using dipolar capillary interactions is demonstrated. A
previously discovered first-order phase transition is exploited and it is shown
how to spontaneously turn off these dipolar capillary interactions by exceeding a
critical field strength, providing unprecedented control of the bottom-up
fabrication of soft materials.
PMID- 25124462
TI - Time trends of physical activity and television viewing time in Brazil: 2006
2012.
AB - BACKGROUND: Despite recent advances in surveillance of physical activity, data on
time trends of physical activity in low and middle-income countries are lacking.
This study describes time trends in physical activity and television viewing
between 2006 and 2012 among Brazilian adults. METHODS: Data from 371,271 adult
participants (18 + years) in the Surveillance System for Risk and Protective
Factors for Chronic Illnesses using Telephone Survey (VIGITEL) were analysed.
Time trends in leisure-time physical activity (>= 5 days/wk; >= 30 min/day),
transportation physical activity (using bicycle or walking for >= 30 minutes per
day as a means of transportation to/from work) and proportion of participants
spending more than three hours per day watching television were analysed. Annual
changes according to sex, age and years of schooling were calculated. RESULTS:
There was an increase in leisure-time physical activity from 12.8% in 2006 to
14.9% in 2012 (annual increase of 1.9%; p < 0.001). This increase was more marked
in younger participants and those with high-school education. Transportation
physical activity decreased 12.9% per year (p < 0.001) from 2006 to 2008 and 5.8%
per year from 2009 to 2012 (p < 0.001). The annual decline in television viewing
time was 5% (p < 0.001) between 2006 and 2009 and 2% (p = 0.16) between 2010 and
2012. CONCLUSION: National survey data from Brazil indicate that leisure-time
physical activity appears to be increasing, while television viewing time appears
to be decreasing in recent years. However, transportation physical activity has
been declining. These data are important for informing national public health
policies.
PMID- 25124461
TI - Alteration of lipid profile in subclinical hypothyroidism: a meta-analysis.
AB - BACKGROUND: Previous studies yielded controversial results about the alteration
of lipid profiles in patients with subclinical hypothyroidism. We performed a
meta-analysis to investigate the association between subclinical hypothyroidism
and lipid profiles. MATERIAL AND METHODS: We searched PubMed, Cochrane Library,
and China National Knowledge Infrastructure articles published January 1990
through January 2014. Dissertation databases (PQDT and CDMD) were searched for
additional unpublished articles. We included articles reporting the relationship
between subclinical hypothyroidism and at least 1 parameter of lipid profiles,
and calculated the overall weighted mean difference (WMD) with a random effects
model. Meta-regression was used to explore the source of heterogeneity among
studies, and the Egger test, Begg test, and the trim and fill method were used to
assess potential publication bias. RESULTS: Sixteen observational studies were
included in our analysis. Meta-analysis suggested that the serum total
cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and total
triglyceride levels were significantly increased in patients with subclinical
hypothyroidism compared with euthyroidism individuals; the WMD were 12.17 mg/dl,
7.01 mg/dl, and 13.19 mg/dl, respectively (P<0.001 for all). No significant
difference was observed for serum high-density lipoprotein cholesterol (HDL-C).
Match strategy was the main source of heterogeneity among studies in TC and LDL-C
analysis. Potential publication bias was found in TC and LDL-C analysis by the
Egger test or Begg test and was not confirmed by the trim and fill method.
CONCLUSIONS: Subclinical hypothyroidism may correlate with altered lipid profile.
Previous studies had limitations in the control of potential confounding factors
and further studies should consider those factors.
PMID- 25124464
TI - Microbial priming of plant and animal immunity: symbionts as developmental
signals.
AB - The functional similarity between root and gut microbiota, both contributing to
the nutrition and protection of the host, is often overlooked. A central
mechanism for efficient protection against pathogens is defense priming, the
preconditioning of immunity induced by microbial colonization after germination
or birth. Microbiota have been recruited several times in evolution as
developmental signals for immunity maturation. Because there is no evidence that
microbial signals are more relevant than endogenous ones, we propose a neutral
scenario for the evolution of this dependency: any hypothetic endogenous signal
can be lost because microbial colonization, reliably occurring at germination or
birth, can substitute for it, and without either positive selection or the
acquisition of new functions. Dependency of development on symbiotic signals can
thus evolve by contingent irreversibility.
PMID- 25124465
TI - Letter to the editor.
PMID- 25124466
TI - Association study of ERbeta, AR, and CYP19A1 genes and MtF transsexualism.
AB - INTRODUCTION: The etiology of male-to-female (MtF) transsexualism is unknown.
Both genetic and neurological factors may play an important role. AIM: To
investigate the possible influence of the genetic factor on the etiology of MtF
transsexualism. METHODS: We carried out a cytogenetic and molecular analysis in
442 MtFs and 473 healthy, age- and geographical origin-matched XY control males.
The karyotype was investigated by G-banding and by high-density array in the
transsexual group. The molecular analysis involved three tandem variable regions
of genes estrogen receptor beta (ERbeta) (CA tandem repeats in intron 5),
androgen receptor (AR) (CAG tandem repeats in exon 1), and CYP19A1 (TTTA tandem
repeats in intron 4). The allele and genotype frequencies, after division into
short and long alleles, were obtained. MAIN OUTCOME MEASURES: We investigated the
association between genotype and transsexualism by performing a molecular
analysis of three variable regions of genes ERbeta, AR, and CYP19A1 in 915
individuals (442 MtFs and 473 control males). RESULTS: Most MtFs showed an
unremarkable 46,XY karyotype (97.96%). No specific chromosome aberration was
associated with MtF transsexualism, and prevalence of aneuploidy (2.04%) was
slightly higher than in the general population. Molecular analyses showed no
significant difference in allelic or genotypic distribution of the genes examined
between MtFs and controls. Moreover, molecular findings presented no evidence of
an association between the sex hormone-related genes (ERbeta, AR, and CYP19A1)
and MtF transsexualism. CONCLUSIONS: The study suggests that the analysis of
karyotype provides limited information in these subjects. Variable regions
analyzed from ERbeta, AR, and CYP19A1 are not associated with MtF transsexualism.
Nevertheless, this does not exclude other polymorphic regions not analyzed.
PMID- 25124467
TI - Are end-of-life practices in Norway in line with ethics and law?
AB - BACKGROUND: End-of-life decisions, including limitation of life prolonging
treatment, may be emotionally, ethically and legally challenging. Euthanasia and
physician-assisted suicide (PAS) are illegal in Norway. A study from 2000
indicated that these practices occur infrequently in Norway. METHODS: In 2012, a
postal questionnaire addressing experience with limitation of life-prolonging
treatment for non-medical reasons was sent to a representative sample of 1792
members of the Norwegian Medical Association (7.7% of the total active doctor
population of 22,500). The recipients were also asked whether they, during the
last 12 months, had participated in euthanasia, PAS or the hastening of death of
non-competent patients. RESULTS: Seventy-one per cent of the doctors responded.
Forty-four per cent of the respondents reported that they had terminated
treatment at the family's request not knowing the patient's own wish, doctors
below 50 and anaesthesiologists more often. Anaesthesiologists more often
reported to have terminated life-prolonging treatment because of resource
considerations. Six doctors reported having hastened the death of a patient the
last 12 months, one by euthanasia, one by PAS and four had hastened death without
patient request. Male doctors and doctors below 50 more frequently reported
having hastened the death of a patient. CONCLUSION: Forgoing life-prolonging
treatment at the request of the family may be more frequent in Norway that the
law permits. A very small minority of doctors has hastened the death of a
patient, and most cases involved non-competent patients. Male doctors below 50
seem to have a more liberal end-of-life practice.
PMID- 25124468
TI - Ambient temperature and prevalence of obesity in the Spanish population: The
Di@bet.es study.
AB - OBJECTIVE: The aim of this study was to examine possible associations between
ambient temperature and obesity in the Spanish population using an ecological
focus. METHODS: The Di@bet.es study is a national, cross-sectional, population
based survey of cardiometabolic risk factors and their association with
lifestyle. SAMPLE: 5,061 subjects in 100 clusters. VARIABLES: Clinical,
demographic and lifestyle survey, physical examination, and blood sampling. The
mean annual temperature ( degrees C) for each study site was collected from the
Spanish National Meteorology Agency (1971-2000). RESULTS: The prevalence rates of
obesity in the different geographical areas divided according to mean annual
temperature quartiles were 26.9% in quartile 1 (10.4-14.5 degrees C), 30.5% in
quartile 2 (14.5-15.5 degrees C), 32% in quartile 3 (15.5-17.8 degrees C), and
33.6% in quartile 4 (17.8-21.3 degrees C) (P = 0.003). Logistic regression
analyses including multiple socio-demographic (age, gender, educational level,
marital status) and lifestyle (physical activity, Mediterranean diet score,
smoking) variables showed that, as compared with quartile 1, the odd ratios for
obesity were 1.20 (1.01-1.42), 1.35 (1.12-1.61), and 1.38 (1.14-1.67) in
quartiles 2, 3, and 4, respectively (P = 0.001 for difference, P < 0.001 for
trend). CONCLUSIONS: Our study reports an association between ambient temperature
and obesity in the Spanish population controlled for known confounders.
PMID- 25124469
TI - Clinical significance of surgical resection for the recurrence of esophageal
cancer after radical esophagectomy.
AB - BACKGROUND: This study aimed to clarify the clinical significance of surgical
resection for recurrent lesions after esophagectomy for esophageal cancer.
METHODS: Recurrence was detected in 113 of 365 consecutive patients who underwent
surgical resection for esophageal cancer, and some treatment was performed for
recurrence in 100 of the 113 patients. The treatments were classified into two
groups: chemotherapy and/or radiation with surgery (surgery group, n = 14) and
chemotherapy and/or radiation without surgery (no surgery group, n = 86). The
outcomes were retrospectively analyzed. RESULTS: Of the 14 patients in the
surgery group, 3 underwent repeated resection. Thus, a total of 22 resections
were performed for these patients. The resected organs were the lymph nodes in
nine patients, the lungs in six patients, local recurrence in two patients,
subcutaneous recurrence in two patients, the liver in one patient, the brain in
one patient, and the parotid gland in one patient. Among the 22 recurrent cases,
20 involved solitary lesions or multiple lesions located in a small resectable
region. When the two groups were compared, the surgery group showed a more
favorable prognosis in terms of both survival after esophagectomy (median
survival time, 103.3 vs 23.1 months; p = 0.0060) and survival after initial
recurrence (92.1 vs 12.2 months; p = 0.0057). CONCLUSIONS: Multimodal treatment
provides a significant benefit for patients with recurrence after esophagectomy
for esophageal cancer. Surgical intervention should be aggressively included in
the treatment strategy when the recurrent lesion is solitary or localized.
PMID- 25124470
TI - Diagnostic performance of multidetector row computed tomography for assessment of
lymph node metastasis in patients with distal rectal cancer.
AB - BACKGROUND: The accurate preoperative diagnosis of depth of tumor invasion and
nodal status in distal rectal cancer is important because neoadjuvant
chemotherapy or lateral pelvic lymph node dissection is indicated for patients
with T3-T4 tumor or nodal involvement. This study aimed to determine the optimal
cutoff value for predicting lymph node metastasis in patients with distal rectal
cancer using multidetector row computed tomography (MDCT). METHODS: The study
investigated 77 patients who had undergone surgery for distal rectal cancer at a
single institution between 2008 and 2011. Diagnostic performance for depth of
tumor invasion and mesorectal and lateral pelvic lymph node metastases was
evaluated. The optimal cutoff value was determined by receiver operating
characteristic curve analysis. RESULTS: For predicting mesorectal and lateral
pelvic lymph node metastasis, MDCT had a sensitivity of 0.36 and 0.89 and a
specificity of 0.78 and 0.97, respectively. The optimal cutoff values of major
and minor axes lengths for predicting mesorectal lymph node metastasis were 6.5
mm and 5.7 mm, respectively. The areas under the curve (AUCs) were 0.82 and 0.88,
respectively. For predicting lateral lymph node metastasis, the optimal cutoff
values were 9 mm for the major axis and 6 mm for the minor axis. Both AUCs were
1. CONCLUSIONS: Using MDCT, the optimal cutoff value of minor axis length for
predicting mesorectal and lateral pelvic lymph node metastases in patients with
distal rectal cancer was 6 mm. The accuracy of MDCT was satisfactory for
predicting lateral pelvic lymph node metastasis.
PMID- 25124471
TI - Intraperitoneal chemotherapy at the time of surgery is not associated with
increased 30-day morbidity and mortality following colorectal resection.
AB - BACKGROUND: In the absence of large randomized trials, the independent
contribution of intraperitoneal chemotherapy (IPC) to morbidity and mortality
(M+M) from cytoreductive surgery remains uncertain. In a multi-institutional
cohort of colorectal surgery patients, we examined the association between M+M
and the use of IPC. METHODS: Patients undergoing an open colorectal resection for
cancer with and without administration of IPC were identified using the American
College of Surgeons National Surgical Quality Improvement Program database (2005
2012). Multivariate logistic regression identified factors associated with 30-day
M+M. Using a propensity score matching method, patients undergoing IPC were
matched 1:3 to non-IPC patients. M+M within the matched cohort was compared using
the chi (2) test. RESULTS: Of the 33,912 patients identified, 188 had concurrent
IPC. The M+M rates were 41 and 30 % with and without IPC, respectively (p =
0.002). In multivariate analysis, IPC was not associated with M+M (odds ratio
0.92; p = 0.62). Using a propensity score match to control for patient and
operative factors, patients who received IPC (n = 188) were matched to patients
who did not receive IPC (n = 365). The M+M rates in the matched cohort did not
significantly differ (41 % with IPC and 45 % without IPC; p = 0.34). Similarly,
mortality (1.1 vs. 2.5 %; p = 0.26) and length of stay (12 vs. 11 days; p = 0.27)
were not affected by IPC status. CONCLUSIONS: After controlling for patient and
operative factors, IPC was not associated with increased M+M following colorectal
resection. The high morbidity observed in patients receiving IPC appears to be
driven by operative factors other than the use of IPC.
PMID- 25124472
TI - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant
peritoneal mesothelioma: a systematic review and meta-analysis.
AB - BACKGROUND: Due to the increased adoption of cytoreductive surgery (CRS) and
hyperthermic intraperitoneal chemotherapy (HIPEC), patients with malignant
peritoneal mesothelioma (MPM) have seen improved outcomes. We aimed to evaluate
and synthesize the recent published literature. METHODS: The review was conducted
according to the recommendation of the Meta-Analysis of Observational Studies in
Epidemiology group with prespecified inclusion and exclusion criteria. The DEALE
method was used to combine mortality rates, and imputation techniques were used
to calculate standard errors. Meta-regression techniques were used to synthesize
data. Publication bias was assessed using funnel plots. RESULTS: Of 6,528
citations collected, 20 articles reporting on 1,047 patients were included in the
analysis. The median age was 51 years (interquartile range 49-55), with 59 % (54
67) female. The median peritoneal carcinomatosis index score was 19 (16-23).
Complete cytoreduction (CC0, 1) was performed in 67 % (46-93 %) of patients.
Pooled estimates of survival yielded a 1-, 3- and 5-year survival of 84, 59, and
42 %, respectively. Patients receiving early postoperative intraperitoneal
chemotherapy [EPIC] (44 %) and those receiving cisplatin intraperitoneal
chemotherapy alone (48 %) or in combination (44 %) had an improved 5-year
survival. CONCLUSIONS: While CRS + HIPEC has led to an improved survival for
patients with MPM compared to historic data, heterogeneity of studies precludes
generalizable inferences. EPIC chemotherapy and cisplatin chemoperfusion may
infer survival benefit.
PMID- 25124460
TI - The Babesia bovis gene and promoter model: an update from full-length EST
analysis.
AB - BACKGROUND: Babesia bovis is an apicomplexan parasite that causes babesiosis in
infected cattle. Genomes of pathogens contain promising information that can
facilitate the development of methods for controlling infections. Although the
genome of B. bovis is publically available, annotated gene models are not highly
reliable prior to experimental validation. Therefore, we validated a preproposed
gene model of B. bovis and extended the associated annotations on the basis of
experimentally obtained full-length expressed sequence tags (ESTs). RESULTS: From
in vitro cultured merozoites, 12,286 clones harboring full-length cDNAs were
sequenced from both ends using the Sanger method, and 6,787 full-length cDNAs
were assembled. These were then clustered, and a nonredundant referential data
set of 2,115 full-length cDNA sequences was constructed. The comparison of the
preproposed gene model with our data set identified 310 identical genes, 342
almost identical genes, 1,054 genes with potential structural inconsistencies,
and 409 novel genes. The median length of 5' untranslated regions (UTRs) was 152
nt. Subsequently, we identified 4,086 transcription start sites (TSSs) and 2,023
transcriptionally active regions (TARs) by examining 5' ESTs. We identified
ATGGGG and CCCCAT sites as consensus motifs in TARs that were distributed around
50 bp from TSSs. In addition, we found ACACA, TGTGT, and TATAT sites, which were
distributed periodically around TSSs in cycles of approximately 150 bp. Moreover,
related periodical distributions were not observed in mammalian promoter regions.
CONCLUSIONS: The observations in this study indicate the utility of integrated
bioinformatics and experimental data for improving genome annotations. In
particular, full-length cDNAs with one-base resolution for TSSs enabled the
identification of consensus motifs in promoter sequences and demonstrated clear
distributions of identified motifs. These observations allowed the illustration
of a model promoter composition, which supports the differences in
transcriptional regulation frameworks between apicomplexan parasites and mammals.
PMID- 25124473
TI - FOXC1 is a critical mediator of EGFR function in human basal-like breast cancer.
AB - BACKGROUND: Human basal-like breast cancer (BLBC) has a poor prognosis and is
often identified by expression of the epidermal growth factor receptor (EGFR).
BLBC remains a major clinical challenge because its pathogenesis is not well
understood, thus hindering efforts to develop targeted therapies. Recent data
implicate the forkhead box C1 (FOXC1) transcription factor as an important
prognostic biomarker and functional regulator of BLBC, but its regulatory
mechanism and impact on BLBC tumorigenesis remain unclear. METHODS: The
association between FOXC1 and EGFR expression in human breast cancer was examined
by immunohistochemistry in formalin-fixed tissues and analysis of the TCGA
database. The regulation of FOXC1 by EGFR activation was investigated in MDA-MB
468 cells using immunoblotting, qRT-PCR, and luciferase activity assays. This
EGFR effect on FOXC1 expression was confirmed using the MDA-MB-468 xenograft
model. RESULTS: Both FOXC1 mRNA and protein levels significantly correlated with
EGFR expression in human breast tumors. EGFR activation induced FOXC1
transcription through the ERK and Akt pathways in BLBC. EGFR inhibition in vivo
reduced FOXC1 expression in xenograft tumors. We also found that FOXC1 knockdown
impaired the effects of EGF on BLBC cell proliferation, migration, and invasion.
CONCLUSIONS: Our findings uncover a novel EGFR-FOXC1 signaling axis critical for
BLBC cell functions, supporting the notion that intervention in the FOXC1 pathway
may provide potential modalities for BLBC treatment.
PMID- 25124475
TI - The impact of a pulsing groundwater table on greenhouse gas emissions in riparian
grey alder stands.
AB - Floods control greenhouse gas (GHG) emissions in floodplains; however, there is a
lack of data on the impact of short-term events on emissions. We studied the
short-term effect of changing groundwater (GW) depth on the emission of (GHG)
carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) in two riparian grey
alder (Alnus incana) stands of different age in Kambja, southern Estonia, using
the opaque static chamber (five replicates in each site) and gas chromatography
methods. The average carbon and total nitrogen content in the soil of the old
alder (OA) stand was significantly higher than in the young alder (YA) stand. In
both stands, one part was chosen for water table manipulation (Manip) and another
remained unchanged with a stable and deeper GW table. Groundwater table
manipulation (flooding) significantly increases CH4 emission (average: YA-Dry
468, YA-Manip 8,374, OA-Dry 468, OA-Manip 4,187 MUg C m(-2) h(-1)) and decreases
both CO2 (average: OA-Dry 138, OA-Manip 80 mg C m(-2) h(-1)) and N2O emissions
(average: OA-Dry 23.1, OA-Manip 11.8 MUg N m(-2) h(-1)) in OA sites. There was no
significant difference in CO2 and CH4 emissions between the OA and YA sites,
whereas in OA sites with higher N concentration in the soil, the N2O emission was
significantly higher than at the YA sites. The relative CO2 and CH4 emissions
(the soil C stock-related share of gaseous losses) were higher in manipulated
plots showing the highest values in the YA-Manip plot (0.03 and 0.0030 % C day(
1), respectively). The soil N stock-related N2O emission was very low achieving
0.000019 % N day(-1) in the OA-Dry plot. Methane emission shows a negative
correlation with GW, whereas the 20 cm depth is a significant limit below which
most of the produced CH4 is oxidized. In terms of CO2 and N2O, the deeper GW
table significantly increases emission. In riparian zones of headwater streams,
the short-term floods (e.g. those driven by extreme climate events) may
significantly enhance methane emission whereas the long-term lowering of the
groundwater table is a more important initiator of N2O fluxes from riparian gley
soils than flood pulses.
PMID- 25124474
TI - Distribution of PCDD/Fs in the fly ash and atmospheric air of two typical
hazardous waste incinerators in eastern China.
AB - Distribution of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) in the fly
ash and atmospheric air of one medical waste incinerator (MWI) and one industrial
hazardous waste incinerator (IHWI) plants were characterized. The PCDD/F
concentrations of the stack gas (fly ash) produced from MWI and IHWI were 17.7
and 0.7 ng international toxic equivalent (I-TEQ)/Nm(3) (4.1 and 2.5 ng I-TEQ/g),
respectively. For workplace air, the total concentrations of PCDD/Fs were 11.32
and 0.28 pg I-TEQ/Nm(3) (819.5 and 15.3 pg/Nm(3)). We assumed that the large
differences of PCDD/F concentrations in workplace air were due to the differences
in chlorine content of the waste, combustion conditions, and other contamination
sources. With respect to the homologue profiles, the concentrations of PCDFs
decreased with the increase of the substituted chlorine number for each site.
Among all of the PCDD/F congeners, 2,3,4,7,8-PeCDF was the most important
contributor to the I-TEQ value accounting for ca. 43 % of two sites. The
gas/particle partition of PCDD/Fs in the atmosphere of the workplace in the MWI
was also investigated, indicating that PCDD/Fs were more associated in the
particle phase, especially for the higher chlorinated ones. Moreover, the ratio
of the I-TEQ values in particle and gas phase of workplace air was 11.0. At last,
the relationship between the distribution of PCDD/Fs in the workplace air and
that from stack gas and fly ash was also analyzed and discussed. The high
correlation coefficient might be a sign for diffuse gas emissions at transient
periods of fumes escaping from the incinerator.
PMID- 25124476
TI - Recent insights into the biology of neuroblastoma.
AB - Neuroblastoma (NB) is an embryonal tumor of the sympathetic nervous system which
accounts for 8-10% of pediatric cancers. It is characterized by a broad spectrum
of clinical behaviors from spontaneous regression to fatal outcome despite
aggressive therapies. Considerable progress has been made recently in the
germline and somatic genetic characterization of patients and tumors. Indeed,
predisposition genes that account for a significant proportion of familial and
syndromic cases have been identified and genome-wide association studies have
retrieved a number of susceptibility loci. In addition, genome-wide sequencing,
copy-number and expression studies have been conducted on tumors and have
detected important gene modifications, profiles and signatures that have strong
implications for the therapeutic stratification of patients. The identification
of major players in NB oncogenesis, including MYCN, ALK, PHOX2B and LIN28B, has
enabled the development of new animal models. Our review focuses on these recent
advances, on the insights they provide on the mechanisms involved in NB
development and their applications for the clinical management of patients.
PMID- 25124477
TI - Anterolateral thigh adipofascial flap in mucosal reconstruction.
AB - IMPORTANCE: This study describes a reliable technique for mucosal reconstruction
of large defects using components of a common free flap technique. OBJECTIVE: To
review the harvest technique and the varied scenarios in which the anterolateral
thigh adipofascial flap (ALTAF) can be used for mucosal restoration in oral
cavity and nasal reconstruction. DESIGN, SETTING, AND PARTICIPANTS: A
retrospective review of the medical records of 51 consecutive patients was
conducted. The patients had undergone ALTAF head and neck reconstruction between
January 2009 and June 2013. Each case was reviewed, and flap survival and goal
oriented results were evaluated. RESULTS: Thirty patients met the inclusion
criteria and were included in the analysis. The mean patient age was 60.6 years.
Reconstruction sites included the tongue, palate, gingiva, floor of the mouth,
and nasal mucosa. All mucosal reconstructions maintained function and form of
replaced and preserved tissues. One patient (3%) experienced flap failure that
was reconstructed with a contralateral adipofascial flap with excellent outcome.
Three patients (10%) required minor flap revisions. There were no other
complications. CONCLUSIONS AND RELEVANCE: The ALTAF is a versatile flap easily
harvested for use in several types of mucosal reconstructions.
PMID- 25124478
TI - Flavor-enhancing properties of mushrooms in meat-based dishes in which sodium has
been reduced and meat has been partially substituted with mushrooms.
AB - The effects of beef substitution with crimini or white mushrooms (Agaricus
bisporus) on the flavor profiles of carne asada and beef taco blends were
measured with a descriptive analysis panel. Sensory mitigation of sodium
reduction through the incorporation of mushrooms was also investigated in the
taco blends. The substitution of beef with mushrooms in the carne asada did not
alter the overall flavor strength of the dish, but the incorporation of 50% or
80% ground mushroom in the beef taco blend did enhance its overall flavor as well
as mushroom, veggie, onion, garlic and earthy flavors, and umami and sweet
tastes. Overall flavor intensity of the 25% reduced-salt version of the 80%
mushroom taco blend matched that of the full-salt versions of the 100% and 50%
beef formulations, thus indicating that the substitution of 80% of the meat with
mushrooms did mitigate the 25% sodium reduction in terms of the overall flavor
impact of the dish, even if it did not quite compensate for the reduction in
salty taste. This proof-of-concept study for the Healthy Flavors Research
Initiative indicates that because of their flavor-enhancing umami principles,
mushrooms can be used as a healthy substitute for meat and a mitigating agent for
sodium reduction in meat-based dishes without loss of overall flavor.
PMID- 25124479
TI - The relation between FoxP3+ regulatory T cells and fungal density in oral
paracoccidioidomycosis: a preliminary study.
AB - Regulatory T (Treg) cells may play an important role in the pathogenesis of
paracoccidioidomycosis (PCM), but data on the role of Treg cells in the context
of oral PCM are still scarce. The objectives of this study were to investigate
the density of FoxP3(+) T regulatory cells in oral PCM and to correlate the
results with the density of Paracoccidioides brasiliensis in the lesions. Cases
of chronic oral PCM seen between 2000 and 2008 were included in this study. The
diagnosis of all lesions was confirmed with histopathological examination and
Grocott-Gomori staining. The quantitative analysis of the viable fungi was
conducted in all cases with Grocott-stained slides. Treg cells were identified
using antibodies against FoxP3. Pearson correlation coefficient was used to test
the correlation between the density of fungi and Treg cells. Results were
considered significant when P < 0.05. A total of 11 cases of oral PCM were
obtained. There was a positive correlation between fungal density and FoxP3(+)
Treg cells density in oral lesions, however, without statistical significance. A
positive relation between Treg cells and fungal density was seen in oral PCM.
Further studies are required to further elucidate the role of these cells in the
pathogenesis of oral PCM, as well the clinical significance of these findings.
PMID- 25124480
TI - The Segond fracture: a bony injury of the anterolateral ligament of the knee.
AB - PURPOSE: The purpose of this study was to investigate the relation of the Segond
fracture with the anterolateral ligament (ALL) of the knee. METHODS: To identify
the soft-tissue structure causative for the Segond fracture, a study was set up
to compare anatomic details of the tibial insertion of the recently characterized
ALL in cadaveric knees (n = 30) with radiologic data obtained from patients (n =
29) with a possible Segond fracture based on an imaging protocol search. The
spatial relation of the ALL footprint with well-identifiable anatomic landmarks
at the lateral aspect of the knee was determined, and this was repeated for the
Segond fracture bed. RESULTS: In all of the included cadaveric knees, a well
defined ALL was found as a distinct ligamentous structure connecting the lateral
femoral epicondyle with the anterolateral proximal tibia. The mean distance of
the center of the tibial ALL footprint to the center of the Gerdy tubercle (GT
ALL distance) measured 22.0 +/- 4.0 mm. The imaging database search identified 26
patients diagnosed with a Segond fracture. The mean GT-Segond distance measured
22.4 +/- 2.6 mm. The observed difference of 0.4 mm (95% confidence interval, -1.5
to 2.2 mm) between the GT-ALL distance and GT-Segond distance was neither
statistically significant (P = .70) nor clinically relevant. CONCLUSIONS: The
results of this study confirmed the hypothesis that the ALL inserts in the region
on the proximal tibia from where Segond fractures consistently avulse, thus
suggesting that the Segond fracture is actually a bony avulsion of the ALL.
CLINICAL RELEVANCE: Although the Segond fracture remains a useful radiographic
clue for indirect detection of anterior cruciate ligament injuries, the Segond
fracture should be considered a frank ligamentous avulsion itself.
PMID- 25124481
TI - Transtibial versus anteromedial portal anterior cruciate ligament reconstruction
using soft-tissue graft and expandable fixation.
AB - PURPOSE: To compare clinical outcomes between transtibial drilling and
anteromedial portal techniques for anterior cruciate ligament (ACL)
reconstruction using soft-tissue grafts secured with expandable fixation.
METHODS: Patients undergoing soft-tissue ACL reconstruction using expandable
fixation between 2007 and 2011 were reviewed for inclusion in this study.
Revision ACL cases were excluded. All surgeries were performed by 1 of 2 sports
medicine fellowship-trained surgeons (T.S.D., K.D.M.). A total of 128 patients
(67 comprising transtibial cohort and 61 comprising anteromedial portal cohort)
had a minimum of 24 months' follow-up (mean, 27 months) and met the inclusion
criteria. The patients were divided into 2 groups based on the method used for
creation of the femoral tunnel. At final follow-up, outcomes were assessed with
KT-1000 (MEDmetric, San Diego, CA) measurements, as well as International Knee
Documentation Committee, Lysholm, and Tegner scores. Data were screened for
normality and skew before use of parametric statistics and were transformed if
necessary. Data were analyzed by 1-way analysis of variance with post hoc paired
comparisons using the Bonferroni approximation. RESULTS: No differences in
demographic characteristics were observed between the 2 groups. There was no
significant difference in postoperative KT-1000 measurements between the 2
cohorts (1.571 +/- 0.2275 mm in transtibial cohort [n = 35] and 1.246 +/- 0.09249
mm in anteromedial cohort [n = 61], P = .1259). A significant improvement in
International Knee Documentation Committee scores was observed in the
anteromedial cohort, increasing from 41 +/- 16 to 89 +/- 7.4 (mean +/- SD) (P <
.0001). Similar changes were observed for the Lysholm score. There was no
significant difference between cohorts for any postoperative scores measured (P >
.2). CONCLUSIONS: Our data show comparable KT-1000 measurements for both
anteromedial and transtibial femoral drilling techniques when using a soft-tissue
graft with expandable fixation. LEVEL OF EVIDENCE: Level IV, therapeutic case
series.
PMID- 25124482
TI - International knee documentation committee knee survey use after anterior
cruciate ligament reconstruction: a 2005-2012 systematic review and world region
comparison.
AB - PURPOSE: The purpose of this review was to evaluate International Knee
Documentation Committee (IKDC) survey use after anterior cruciate ligament
reconstruction compared with other surveys and determine evidence levels and
methodologic study quality by world region. METHODS: The Medline database was
searched from January 2005 through December 2012. RESULTS: We identified 421
studies and 33 surveys. Europe and Australia had more objective and subjective
IKDC form use (chi(2) = 9.6, P = .047). Europe and Asia had more objective IKDC
form use (chi(2) = 19.4, P = .001). Asia had more Lysholm knee scale use (chi(2)
= 29.9, P < .0001). Europe had more Tegner Activity Level scale (chi(2) = 31.7, P
< .0001) and Knee Injury and Osteoarthritis Outcome Score (chi(2) = 20.5, P <
.0001) use. North America and Australia had more Cincinnati or Noyes knee rating
scale use (chi(2) = 21, P < .0001). Asia and Australia had more studies with
greater than 60 subjects (chi(2) = 24.4, P = .018). Europe had more studies with
greater than 24 months' follow-up (chi(2) = 18.4, P = .018). Asia had more
studies with adequate surgical descriptions (chi(2) = 33.2, P < .0001). North
America had more studies with well-described rehabilitation (chi(2) = 18.2, P =
.02). Europe had more studies with confirmed recruitment (chi(2) = 12.9, P =
.012). Australia and North America had more studies with confirmed independent
investigators (chi(2) = 11.1, P = .026). Europe had more studies with greater
than 80% recruitment (chi(2) = 16.0, P = .04). Methodologically stronger studies
used the objective IKDC survey (P < .0001), the objective and subjective IKDC
survey (P = .002), or the Cincinnati or Noyes scale (P = .002). This group also
made greater use of the Tegner scale (P = .013). CONCLUSIONS: Objective and
subjective IKDC form use is comparable with Lysholm and Tegner scale use.
Objective and subjective IKDC form use in combination with the Tegner Activity
Level scale is recommended. LEVEL OF EVIDENCE: Level IV, systematic review of
Level I-IV studies.
PMID- 25124483
TI - Cardiovascular effects of methylphenidate, amphetamines and atomoxetine in the
treatment of attention-deficit hyperactivity disorder: an update.
AB - Several million children and a growing number of adults are currently being
treated for attention-deficit hyperactivity disorder (ADHD) worldwide. Concerns
have been expressed about possible cardiac effects of the common treatments,
namely methylphenidate, amphetamines and atomoxetine. Small increases in mean
heart rate (HR) and mean blood pressure (BP) have been reported for all three
drugs, but most of the studies have not yielded statistically significant
results. These studies also have limitations, particularly regarding the lack of
accepted and standardised measurement methods. Several large studies of the very
rare phenomenon of sudden death in children have failed to show any convincing
association with ADHD treatment. Whether minor increases in HR and BP have a
cumulative effect over many years and have a long-term adverse effect on
cardiovascular health remains undetermined.
PMID- 25124484
TI - Ciona intestinalis NADH dehydrogenase NDX confers stress-resistance and extended
lifespan on Drosophila.
AB - An assembled cDNA coding for the putative single-subunit NADH dehydrogenase (NDX)
of Ciona intestinalis was introduced into Drosophila melanogaster. The encoded
protein was found to localize to mitochondria and to confer rotenone-insensitive
substrate oxidation in organello. Transgenic flies exhibited increased resistance
to menadione, starvation and temperature stress, and manifested a sex and diet
dependent increase in mean lifespan of 20-50%. However, NDX was able only weakly
to complement the phenotypes produced by the knockdown of complex I subunits.
PMID- 25124486
TI - [Invasive pneumococcal disease in the Community of Valencia. Six years of
surveillance (2007-2012)].
AB - INTRODUCTION: The introduction of conjugated anti-pneumonia vaccines has led to a
change in the epidemiology of Invasive Pneumococcal Disease (IPD). The aim of
this study is to describe the trends in IPD in the Community of Valencia during
the period 2007-2012. MATERIAL AND METHODS: A retrospective, descriptive and
longitudinal study was conducted on IPD in the Community of Valencia during the
period 2007-2012, The information sources used were the Epidemiological
Surveillance Analysis (Analisis de la Vigilancia Epidemiologica (AVE)) and the
Valencian Microbiology Network (Red Microbiologica Valenciana (RedMIVA)) of the
Valencia Health Department. RESULTS: The incidence of IPD decreased between 2007
and 2012 in all age groups, mainly in the under 5 year-olds, dropping from 30.5
cases to 12.3 cases per 10(5) inhabitants (p< .001). Pneumonia was the principal
presentation of the disease, with a decrease in its rates from 6.9 to 4.1 cases
per 10(5) inhabitants (p< .001). A gradual, non-significant, reduction from 26%
to 12% (p=.23) was observed in the proportion of cases due to the serotypes
contained in the heptavalent vaccine (PCV7), mainly in the under 5 year-olds. The
cases due to additional serotypes in 13-valent conjugated vaccine (1, 3, 5, 6A,
7F and 19A) also showed a decreasing trend, mainly in vaccinated under 5 year
olds (52.6% vs 14.3%; p=.03), while the cases due to non-vaccine serotypes
significantly increased from 42.3% to 56.7% in the general population (p=.002),
and from 47.4% to 78.6% in vaccinated under 5 year-olds (p=.08). CONCLUSIONS: The
results of this study show a reduction in the incidence of IPD, with a decrease
in the proportion of cases produced by vaccine serotypes, and an increase in the
proportion of those not vaccinated. Epidemiological Surveillance is necessary to
monitor the trends in the disease.
PMID- 25124485
TI - A multicentre sero-behavioural survey for hepatitis B and C, HIV and HTLV among
people who inject drugs in Germany using respondent driven sampling.
AB - BACKGROUND: People who inject drugs are at high risk for hepatitis B, hepatitis C
and HIV. HTLV was reported by neighboring countries to be prevalent in this
population, but the situation for Germany is unclear. To generate seroprevalence
and related behavioural data and to enhance prevention efforts against these
infections for drug users in Germany, a multicentre sero- and behavioural survey
was initiated. People who inject drugs are not well reached by services for
testing and counselling for blood-borne infections in Germany. An interventional
part of the study is intended to prove feasibility and acceptance of testing and
counselling in low-threshold drop-in settings. METHODS/DESIGN: Between May 2011
and March 2015, eligible participants (persons having injected drugs within the
last 12 months, aged 16 years+, and living in the study city) are recruited by
respondent driven sampling, using low-threshold drop-in facilities as study-sites
in eight German cities with large drug scenes. Calculated sample size is 2,033
participants. Capillary blood samples collected as dried blood spots are
anonymously tested for serological and molecular markers of hepatitis B and C,
HIV, and HTLV I and II. A detailed face-to-face-interview about hepatitis- and
HIV-related knowledge, former testing, imprisonment, sexual and injecting risk
behaviour is conducted with participants. Staff is trained to offer pre- and post
test-counselling of blood-borne infections and HIV rapid testing to participants.
DISCUSSION: We chose respondent driven sampling for recruitment of participants
to improve representativeness of results. Persons, who are not reached by the
facility where the study is conducted, are aimed to be included by recruitment
through their personal social network of injecting drug users. To reduce
differential biases in the questions on knowledge of transmission and prevention
of infections, we present true statements on hepatitis B, C and HIV, their
possible routes of transmission and measures of prevention to participants.
Participants are told that the statements are true and are asked to answer if
they knew this fact already or if it is new to them. In case of knowledge gaps
they are offered free targeted counselling as well as free HIV rapid testing and
post-test counselling of HIV and hepatitis test results.
PMID- 25124487
TI - [Does the prescribing of antibiotics in paediatrics improve after a
multidisciplinary intervention?].
AB - Antibiotics overuse is linked to elevated antimicrobial resistance. In Aragon,
Spain, the highest antibiotic prescription rates occur among children from 1 to 4
years old. The rate of use in this age group is over 60%. AIM: To evaluate the
effect of multi-faceted intervention on Primary Care paediatricians to reduce
antibiotic use and to improve antibiotic prescribing for paediatric outpatients.
METHODS: Outpatient antimicrobial prescribing was analysed before and after an
intervention in paediatricians. The intervention included a clinical education
session about diagnosis and treatment in the most prevalent paediatric infectious
diseases, a clinical interview and communication skills, a workshop on rapid
Streptococcus antigen detection test and patient information leaflets and useful
internet websites for parents. The control group included paediatricians without
this educational intervention on antibiotics. RESULTS: Antibiotic prescribing
decreased from 19.17 defined daily doses per 1000 inhabitants/day (DID) to 14.36
DID among intervention paediatricians vs 19.84 DID to 16.02 DID in controls. The
decreasing was higher in the intervention group, but the effect was not
statistically significant. Macrolides and broad-spectrum penicillins prescribing
decreased in both groups. CONCLUSION: Antibiotic prescribing decreased, but there
were no statistically significant differences between the two groups. The high
satisfaction of paediatricians in the intervention group makes it necessary to
continue with these kinds of strategies to improve antibiotic use in outpatients.
PMID- 25124488
TI - [Procedure for the marketing authorization of an antibacterial agent].
AB - The marketing authorization of a new medicinal product is the first step before
being placed on the market, and includes the full investigation programme. In
order to ensure their quality, safety and efficacy, medicinal products are
closely regulated from their initial phases of investigation to their use in
clinical practice. For registration purposes, the results of all the clinical and
preclinical studies, along with quality data and the description of the
manufacturing process should be submitted. All information collected is presented
for review by the competent authority. The European Medicines Agency regulates
the registration of medicines in Europe, and national agencies in each EU member
state are responsible for the assessment of the marketing authorisation
application. To facilitate the development of clinical programmes, there is a
common framework for the evaluation of an antibacterial, which includes
guidelines and an addendum, detailing the specific requirements that must be
carried out in clinical trials to assess the efficacy and safety for most of the
infections.
PMID- 25124490
TI - Beneficial effect of Oligonol supplementation on sweating response under heat
stress in humans.
AB - Oligonol is a low-molecular weight polyphenol that possesses antioxidant and anti
inflammatory properties. However, nothing is known regarding the impact of
Oligonol on sudomotor activity. This study investigated the effects of Oligonol
supplementation on sudomotor activity during heat load in humans. Initially, we
conducted a placebo-controlled, cross-over trial where participants took a daily
dose of Oligonol 200 mg or placebo for one week. After a 2 week washout period,
the subjects were switched to the other study arm. As a heat load, half-body
immersion into hot water (42 +/- 0.5 degrees C for 30 min) was performed in an
automated climate chamber. Tympanic and skin temperatures were measured.
Sudomotor activity, including onset time, sweat rate (SR) and volume (SV), active
sweat gland density (ASGD), and sweat gland output (SGO), was tested in four or
eight areas of skin. When compared with placebo, Oligonol attenuated increases in
tympanic and skin temperatures after the heat load. There was an increasing trend
in local sweat onset time, but there was a decrease in local SR, SV, ASGD, and
SGO for Oligonol compared to placebo. The mean ASGD was significantly higher in
the Oligonol group than in the placebo group for 10, 20, and 30 min. This study
demonstrates that Oligonol appears to be worthy of consideration as a natural
supplement to support more economical use of body fluids against heat stress.
PMID- 25124489
TI - [Acute outbreak of hepatitis C in human immunodeficiency virus-infected
patients].
AB - BACKGROUND: Recent studies suggest an increased incidence of acute infection with
hepatitisC virus (AHC) in men who have sex with men (MSM) co-infected with HIV.
Early treatment with interferon-alpha, alone or in combination with ribavirin,
significantly reduces the risk of chronic evolution. METHODS: This retrospective
study includes all HIV patients with AHC in our centre from 2003 to March 2013.
AHC was defined by seroconversion of HCV antibodies and detection of serum HCV
RNA. RESULTS: 93 episodes of AHC were diagnosed in 89 patients. All but three
were MSM with a history of unprotected sex. Thirty-seven (40%) patients had other
associated sexually transmitted disease. The 29% (27) had any symptoms suggestive
of AHC. HCV genotype 4 was the most common (41%), followed by genotype1. Seventy
patients started treatment with interferon-alfa and weight-adjusted ribavirin.
Currently 46 have completed treatment and follow-up, reaching 26 of them (56.5%)
sustained viral response. CONCLUSIONS: The incidence of AHC in HIV MSM patients
from our centre has increased exponentially in recent years; sexual transmission
remains the main route of infection. Early treatment with interferon-alpha and
ribavirin achieved a moderate response in these patients.
PMID- 25124491
TI - Monitoring fetal immune development in human pregnancies: current concepts and
future goals.
AB - The vast majority of the current knowledge on immune development in the fetal
period has been gained from animal studies, particularly from mouse models. This
has led to a great improvement in our current understanding of immune ontogeny.
However, it has also become clear that in many ways the mouse model of pregnancy
differs from the situation in human pregnancy, such as the degree and importance
of trophoblast invasion, the kind of MHC class repertoire of the extravillous
trophoblast cells, and differences concerning the development and regulation of T
cells. It will be of paramount importance to develop non-invasive screening
methods to assess fetal immune development in humans. The focus of this mini
review is to discuss how prenatal ultrasound evaluation can be used as a tool to
monitor fetal immune development in human pregnancies. To identify the fetuses at
risk of immune disorders could be the first step to developing prevention
strategies in the future.
PMID- 25124498
TI - Seclusion and restraint as measures of the quality of hospital care: any
exceptions?
AB - The Joint Commission has recently included seclusion and restraint as quality-of
care indicators for hospital-based inpatient psychiatric services. Their
inclusion is the result of abuse of these practices, wide variation across
hospitals, and cultural influences, including the consumer and recovery
movements. Over the next few years, these indicators will increasingly influence
treatment modalities available to hospitalized patients. This Open Forum provides
a brief history of changing attitudes toward use of seclusion and restraint. It
describes three clinical scenarios that highlight appropriate and humane use of
seclusion and restraint and that illustrate the clinical complexities associated
with their use. Potential unforeseen consequences of the reduction or elimination
of seclusion and restraint are described.
PMID- 25124495
TI - Circulating omega-6 polyunsaturated fatty acids and total and cause-specific
mortality: the Cardiovascular Health Study.
AB - BACKGROUND: Although omega-6 polyunsaturated fatty acids (n-6 PUFA) have been
recommended to reduce coronary heart disease (CHD), controversy remains about
benefits versus harms, including concerns over theorized proinflammatory effects
of n-6 PUFA. We investigated associations of circulating n-6 PUFA including
linoleic acid (the major dietary PUFA), gamma-linolenic acid, dihomo-gamma
linolenic acid, and arachidonic acid, with total and cause-specific mortality in
the Cardiovascular Health Study, a community-based U.S. cohort. METHODS AND
RESULTS: Among 2792 participants(aged >=65 years) free of cardiovascular disease
at baseline, plasma phospholipid n-6 PUFA were measured at baseline using
standardized methods. All-cause and cause-specific mortality, and total incident
CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA
with risk were assessed by Cox regression. During 34 291 person-years of follow
up (1992-2010), 1994 deaths occurred (678 cardiovascular deaths), with 427 fatal
and 418 nonfatal CHD, and 154 fatal and 399 nonfatal strokes. In multivariable
models, higher linoleic acid was associated with lower total mortality, with
extreme-quintile hazard ratio =0.87 (P trend=0.005). Lower death was largely
attributable to cardiovascular disease causes, especially nonarrhythmic CHD
mortality (hazard ratio, 0.51; 95% confidence interval, 0.32-0.82; P
trend=0.001). Circulating gamma-linolenic acid, dihomo-gamma-linolenic acid, and
arachidonic acid were not significantly associated with total or cause-specific
mortality (eg, for arachidonic acid and CHD death, the extreme-quintile hazard
ratio was 0.97; 95% confidence interval, 0.70-1.34; P trend=0.87). Evaluated
semiparametrically, linoleic acid showed graded inverse associations with total
mortality (P=0.005). There was little evidence that associations of n-6 PUFA with
total mortality varied by age, sex, race, or plasma n-3 PUFA. Evaluating both n-6
and n-3 PUFA, lowest risk was evident with highest levels of both. CONCLUSIONS:
High circulating linoleic acid, but not other n-6 PUFA, was inversely associated
with total and CHD mortality in older adults.
PMID- 25124497
TI - Maintenance of the nutritional prognostic index predicts survival in patients
with unresectable metastatic colorectal cancer.
AB - PURPOSE: Nutrition and immunity significantly affect the progression of cancer in
cancer patients. Therefore, the evaluation of the nutritional and immune status
would be useful as a prognostic factor and to determine the optimal treatment
strategy for patients with unresectable metastatic colorectal cancer who are
receiving chemotherapy. The aim of this retrospective study was to evaluate the
prognostic significance of the nutritional and immune status in patients with
unresectable metastatic colorectal cancer treated with chemotherapy. METHODS: We
retrospectively reviewed 80 patients with colorectal cancer. A total of 22
patients had metachronous unresectable cancer, and 58 patients had synchronous
unresectable cancer. All patients underwent combination chemotherapy with
oxaliplatin or irinotecan plus 5-fluorouracil/leucovorin as first-line
chemotherapy. We then examined the correlations between the Onodera's prognostic
nutritional index (OPNI) and the patients' clinicopathological features. The OPNI
was calculated as follows: 10 * serum albumin (g/dl) + 0.005 * total lymphocyte
count (per mm(3)). According to the receiver operating characteristic (ROC) curve
analysis, the cutoff value for OPNI was 44.5. RESULTS: Patients with a
pretreatment OPNI of ?44.5 demonstrated a longer OS than those with a
pretreatment OPNI of <44.5. Moreover, we categorized these patients into four
groups according to the combination of the pre- and post-treatment OPNI. The
patients in the group with both OPNIs >=44.5 exhibited a better prognosis
compared to the other group (p = 0.001). CONCLUSION: The OPNI is considered to be
a useful marker for predicting the long-term outcome in patients who receive
chemotherapy for unresectable metastatic colorectal cancer.
PMID- 25124499
TI - Exploring the genome-wide relation between copy number status and microRNA
expression.
AB - The deregulation of miRNAs has been associated with several different cancer
types. Deregulation occurs in several ways, but generally little is known about
the basis for the distorted expression of miRNAs. We investigated the relation
between copy number status and miRNA expression at the genome-wide level using
cytogenetic and array-based methods to characterize genomic aberrations in
hematopoietic cell lines. For the same cell lines, we obtained global miRNA
expression profiles, and analyzed the genome-wide correlation using the
Spearman's rank test. This analysis showed that the expression of only a two
miRNAs (miR-324-5p encoded by MIR324 at 17p13.1 and miR-660 encoded by MIR660 at
Xp11.23) was influenced by copy number status. Our data imply that no direct
relation between copy number status and miRNA expression exists in the
investigated cell lines.
PMID- 25124496
TI - Cardiac CaM Kinase II genes delta and gamma contribute to adverse remodeling but
redundantly inhibit calcineurin-induced myocardial hypertrophy.
AB - BACKGROUND: Ca(2+)-dependent signaling through CaM Kinase II (CaMKII) and
calcineurin was suggested to contribute to adverse cardiac remodeling. However,
the relative importance of CaMKII versus calcineurin for adverse cardiac
remodeling remained unclear. METHODS AND RESULTS: We generated double-knockout
mice (DKO) lacking the 2 cardiac CaMKII genes delta and gamma specifically in
cardiomyocytes. We show that both CaMKII isoforms contribute redundantly to
phosphorylation not only of phospholamban, ryanodine receptor 2, and histone
deacetylase 4, but also calcineurin. Under baseline conditions, DKO mice are
viable and display neither abnormal Ca(2+) handling nor functional and structural
changes. On pathological pressure overload and beta-adrenergic stimulation, DKO
mice are protected against cardiac dysfunction and interstitial fibrosis. But
surprisingly and paradoxically, DKO mice develop cardiac hypertrophy driven by
excessive activation of endogenous calcineurin, which is associated with a lack
of phosphorylation at the auto-inhibitory calcineurin A site Ser411. Likewise,
calcineurin inhibition prevents cardiac hypertrophy in DKO. On exercise
performance, DKO mice show an exaggeration of cardiac hypertrophy with increased
expression of the calcineurin target gene RCAN1-4 but no signs of adverse cardiac
remodeling. CONCLUSIONS: We established a mouse model in which CaMKII's activity
is specifically and completely abolished. By the use of this model we show that
CaMKII induces maladaptive cardiac remodeling while it inhibits calcineurin
dependent hypertrophy. These data suggest inhibition of CaMKII but not
calcineurin as a promising approach to attenuate the progression of heart
failure.
PMID- 25124500
TI - Psychometric properties of the social phobia and social interaction anxiety
scales: evidence of construct equivalence in an African American sample.
AB - This study evaluated the psychometric properties of the Social Phobia Scale and
Social Interaction Anxiety scale in a community sample of African Americans. We
conducted a confirmatory factor analysis of the combined scales comparing the
data to 2- and 3-factor solutions commonly reported in the literature. The
results indicated that neither solution produce an adequate fit to the data in
this study. We then proceeded to conduct an exploratory factor analysis within a
confirmatory framework of both scales. While we were able to extract a 2-factor
solution from the data, the item composition of the factors was somewhat
different for African Americans than what is typically reported in non-Hispanic
White samples. While we conclude that use of the two social anxiety scales is
warranted, we make recommendations regarding the interpretation of both scales
with African Americans.
PMID- 25124494
TI - Integrating genetic, transcriptional, and functional analyses to identify 5 novel
genes for atrial fibrillation.
AB - BACKGROUND: Atrial fibrillation (AF) affects >30 million individuals worldwide
and is associated with an increased risk of stroke, heart failure, and death. AF
is highly heritable, yet the genetic basis for the arrhythmia remains
incompletely understood. METHODS AND RESULTS: To identify new AF-related genes,
we used a multifaceted approach, combining large-scale genotyping in 2 ethnically
distinct populations, cis-eQTL (expression quantitative trait loci) mapping, and
functional validation. Four novel loci were identified in individuals of European
descent near the genes NEURL (rs12415501; relative risk [RR]=1.18; 95% confidence
interval [CI], 1.13-1.23; P=6.5*10(-16)), GJA1 (rs13216675; RR=1.10; 95% CI, 1.06
1.14; P=2.2*10(-8)), TBX5 (rs10507248; RR=1.12; 95% CI, 1.08-1.16; P=5.7*10(
11)), and CAND2 (rs4642101; RR=1.10; 95% CI, 1.06-1.14; P=9.8*10(-9)). In
Japanese, novel loci were identified near NEURL (rs6584555; RR=1.32; 95% CI, 1.26
1.39; P=2.0*10(-25)) and CUX2 (rs6490029; RR=1.12; 95% CI, 1.08-1.16; P=3.9*10(
9)). The top single-nucleotide polymorphisms or their proxies were identified as
cis-eQTLs for the genes CAND2 (P=2.6*10(-19)), GJA1 (P=2.66*10(-6)), and TBX5
(P=1.36*10(-5)). Knockdown of the zebrafish orthologs of NEURL and CAND2 resulted
in prolongation of the atrial action potential duration (17% and 45%,
respectively). CONCLUSIONS: We have identified 5 novel loci for AF. Our results
expand the diversity of genetic pathways implicated in AF and provide novel
molecular targets for future biological and pharmacological investigation.
PMID- 25124502
TI - Comparison of the Penn State Worry Questionnaire (PSWQ) and abbreviated version
(PSWQ-A) in a clinical and non-clinical population of older adults.
AB - The Penn State Worry Questionnaire (PSWQ) is a widely used measure of worry
severity. An 8-item abbreviated version (PSWQ-A) has been developed as a brief
screening measure, although there are limited studies assessing the psychometric
properties of this measure in a large geriatric population. The aim of this study
was to assess the utility of the PSWQ-A compared to the full PSWQ, to identify
pathological worry in an older adult sample (N=108) of clinically anxious and
depressed older adults, compared to a non-clinical sample (N=53). The PSWQ and
PSWQ-A were found to have similarly adequate reliability and validity. The factor
structure of the PSWQ-A was replicated, but not for the PSWQ. Both measures
accurately distinguished between clinical and non-clinical status with similar
sensitivity and specificity. These findings indicate the PSWQ-A is a useful
measure for screening or epidemiological studies assessing worry in geriatric
populations.
PMID- 25124501
TI - PTSD symptom severity and psychiatric comorbidity in recent motor vehicle
accident victims: a latent class analysis.
AB - We conducted a latent class analysis (LCA) on 249 recent motor vehicle accident
(MVA) victims to examine subgroups that differed in posttraumatic stress disorder
(PTSD) symptom severity, current major depressive disorder and alcohol/other drug
use disorders (MDD/AoDs), gender, and interpersonal trauma history 6-weeks post
MVA. A 4-class model best fit the data with a resilient class displaying
asymptomatic PTSD symptom levels/low levels of comorbid disorders; a mild
psychopathology class displaying mild PTSD symptom severity and current MDD; a
moderate psychopathology class displaying severe PTSD symptom severity and
current MDD/AoDs; and a severe psychopathology class displaying extreme PTSD
symptom severity and current MDD. Classes also differed with respect to gender
composition and history of interpersonal trauma experience. These findings may
aid in the development of targeted interventions for recent MVA victims through
the identification of subgroups distinguished by different patterns of
psychiatric problems experienced 6-weeks post-MVA.
PMID- 25124503
TI - Parental changes after involvement in their anxious child's cognitive behavior
therapy.
AB - OBJECTIVE: Specific parental behaviors and cognitions are associated with child
anxiety. Studies informing us of the directionality of the associations are
lacking. We investigated the effect of parental involvement in children's anxiety
treatment on parental behaviors and cognitions. METHOD: Children (N=54, 7-12
years) and parents were randomly allocated to different treatment groups
(involved, not involved). Observed behavior, self-reported behavior and
cognitions were assessed separately for mothers and fathers at pre-,
posttreatment and follow-up. RESULTS: There were no differences over time for
self-reported parental efficacy and observed negativity, but self-reported
autonomy granting increased for both groups over time. Differential effects were
found between groups for observed paternal over-involvement (fathers involved in
treatment showed a more rapid decrease) and self-reported maternal autonomy
granting (non-involved mothers showed a greater increase). CONCLUSION: Our
findings suggest that child anxiety significantly influences parental behaviors
and cognitions. Child therapy may successfully change the family system.
PMID- 25124504
TI - Implicit affective evaluation bias in hypochondriasis: findings from the Affect
Misattribution Procedure.
AB - Cognitive theories of hypochondriasis (HYP) suggest that catastrophic
misinterpretations of benign body sensations are a core feature for the
maintenance of the disorder. There is tentative support from an analog sample
that the interpretation of illness-related information also involves an implicit
affective component. This is the first study to examine this negative affective
evaluation bias implicitly in patients with HYP. An adapted version of the Affect
Misattribution Procedure (AMP) with illness, symptom and neutral primes was used
in 80 patients with HYP, and compared to 83 patients with an anxiety disorder
(AD), as well as 90 healthy controls (CG). The HYP group showed significantly
more negative affective reactions in illness prime trials, compared to both
control groups, as well as more negative implicit evaluations on symptom prime
trials, compared to the CG. Significant inverse relationships were observed only
between the implicit evaluations of illness words and health anxiety
questionnaires. Thus, an implicit negative affective evaluation bias of serious
illnesses rather than symptoms is a unique feature of HYP.
PMID- 25124505
TI - Peeking into the black box: mechanisms of action for anger management treatment.
AB - We investigated potential mechanisms of action for anger symptom reductions,
specifically, the roles of anger regulation skills and therapeutic alliance on
changes in anger symptoms, following group anger management treatment (AMT) among
combat veterans with posttraumatic stress disorder (PTSD). Data were drawn from a
published randomized controlled trial of AMT conducted with a racially diverse
group of 109 veterans with PTSD and anger symptoms residing in Hawaii. Results of
latent growth curve models indicated that gains in calming skills predicted
significantly larger reductions in anger symptoms at post-treatment, while the
development of cognitive coping and behavioral control skills did not predict
greater symptom reductions. Therapeutic alliance had indirect effects on all
outcomes mostly via arousal calming skills. Results suggest that generalized
symptom reduction may be mediated by development of skills in calming
physiological arousal. In addition, arousal reduction skills appeared to enhance
one's ability to employ other anger regulation skills.
PMID- 25124506
TI - The relationship between the alternative exon 7 splice variant of the BF gene and
MHC-related Marek's disease resistance in chickens.
AB - The study was to analyse the relationship between the alternative exon 7 splice
variant of the BF gene and MHC-related Marek's disease (MD) resistance in
chickens. The experiment first determined whether or not the cocks of Xiayan
chickens have alternative splicing-out of the exon 7 of the BF gene from
peripheral blood leucocytes (PBLs). Then, selected two groups: Group K included
the offspring of the selected cocks which have no alternative splicing-out of the
exon 7 of the BF gene; Group Y included the offspring of the selected cocks which
have alternative splicing-out of the exon 7 of the BF gene. All hens used in the
cross-breeding were non-selected. The experimental chickens were challenged with
a very virulent strain of Marek's disease virus (MDV) at 4 days old and were
raised for 12 weeks. At this time, all the surviving chickens were killed and
necropsy was also performed during the experiment whenever chickens died from the
infection. Tumour incidence and mortality were calculated using SPSS, and the
tissues were collected to detect MDV by PCR. The results showed that the
mortalities of Group K and Y were 52.75% and 70.65%, respectively; and that the
tumour incidences of non-alternative splicing-out of the exon 7 of the BF for
Groups K and Y were 15.38% and 38.89%, respectively; the tumour incidences for
the alternative splicing-out of the exon 7 were 46.15% and 56.76%, respectively.
The results demonstrated the tumour incidence was highly related with the
alternative exon 7 splice variant of the BF gene (P < 0.05).
PMID- 25124507
TI - Cognitive Risk Factors for Specific Learning Disorder: Processing Speed, Temporal
Processing, and Working Memory.
AB - High comorbidity rates between reading disorder (RD) and mathematics disorder
(MD) indicate that, although the cognitive core deficits underlying these
disorders are distinct, additional domain-general risk factors might be shared
between the disorders. Three domain-general cognitive abilities were investigated
in children with RD and MD: processing speed, temporal processing, and working
memory. Since attention problems frequently co-occur with learning disorders, the
study examined whether these three factors, which are known to be associated with
attention problems, account for the comorbidity between these disorders. The
sample comprised 99 primary school children in four groups: children with RD,
children with MD, children with both disorders (RD+MD), and typically developing
children (TD controls). Measures of processing speed, temporal processing, and
memory were analyzed in a series of ANCOVAs including attention ratings as
covariate. All three risk factors were associated with poor attention. After
controlling for attention, associations with RD and MD differed: Although
deficits in verbal memory were associated with both RD and MD, reduced processing
speed was related to RD, but not MD; and the association with RD was restricted
to processing speed for familiar nameable symbols. In contrast, impairments in
temporal processing and visuospatial memory were associated with MD, but not RD.
PMID- 25124508
TI - Acid/base switching of the tautomerism and conformation of a dioxoporphyrin for
integrated binary subtraction.
AB - Compared with most of the reported logic devices based on the supramolecular
approach, systems based on individual molecules can avoid challenging
construction requirements. Herein, a novel dioxoporphyrin DPH22 was synthesized
and two of its tautomers were characterized by single-crystal X-ray diffraction
studies. Compound DPH22 exhibits multichannel controllable stepwise
tautomerization, protonation, and deprotonation processes through interactions
with H(+) and F(-) ions. By using the addition of H(+) and F(-) ions as inputs
and UV/Vis absorption values at lambda=412, 510, 562, and 603 nm as outputs, the
controlled tautomerism of DPH22 has been successfully used for the construction
of an integrated molecular level half-subtractor and comparator. In addition,
this acid/base-switched tautomerism is reversible, thus endowing the system with
ease of reset and recycling; consequently, there is no need to modulate
complicated intermolecular interactions and electron-/charge-transfer processes.
PMID- 25124509
TI - Neuroimaging in social anxiety disorder-a meta-analytic review resulting in a new
neurofunctional model.
AB - Social anxiety disorder (SAD) is one of the most frequent anxiety disorders. The
landmark meta-analysis of functional neuroimaging studies by Etkin and Wager
(2007) revealed primarily the typical fear circuit as overactive in SAD. Since
then, new methodological developments such as functional connectivity and more
standardized structural analyses of grey and white matter have been developed. We
provide a comprehensive update and a meta-analysis of neuroimaging studies in SAD
since 2007 and present a new model of the neurobiology of SAD. We confirmed the
hyperactivation of the fear circuit (amygdala, insula, anterior cingulate and
prefrontal cortex) in SAD. In addition, task-related functional studies revealed
hyperactivation of medial parietal and occipital regions (posterior cingulate,
precuneus, cuneus) in SAD and a reduced connectivity between parietal and limbic
and executive network regions. Based on the result of this meta-analysis and
review, we present an updated model of SAD adopting a network-based perspective.
The disconnection of the medial parietal hub in SAD extends current frameworks
for future research in anxiety disorders.
PMID- 25124511
TI - The need of continuous focus on improved mentoring of trainees and young
investigators in the field of andrology: highlights of current programs and
opportunities for the future.
PMID- 25124512
TI - Lessons learned in andrology: learning from experience - getting it wrong is
alright.
PMID- 25124510
TI - Mindfulness-based cognitive therapy versus psychoeducational intervention in
bipolar outpatients with sub-threshold depressive symptoms: a randomized
controlled trial.
AB - BACKGROUND: The presence of depressive subsyndromal symptoms (SS) in bipolar
disorder (BD) increases the risk of affective relapse and worsens social,
cognitive functioning, and quality of life. Nonetheless, there are limited data
on how to optimize the treatment of subthreshold depressive symptoms in BD.
Mindfulness-Based Cognitive Therapy (MBCT) is a psychotherapeutic intervention
that has been shown effective in unipolar depression. The assessment of its
clinical effectiveness and its impact on biomarkers in bipolar disorder patients
with subsyndromal depressive symptoms and psychopharmacological treatment is
needed. METHODS/DESIGN: A randomized, multicenter, prospective, versus active
comparator, evaluator-blinded clinical trial is proposed. Patients with BD and
subclinical or mild depressive symptoms will be randomly allocated to: 1) MBCT
added to psychopharmacological treatment; 2) a brief structured group
psychoeducational intervention added to psychopharmacological treatment; 3)
standard clinical management, including psychopharmacological treatment.
Assessments will be conducted at screening, baseline, post-intervention (8 weeks)
and 4 month follow-up post-intervention. The aim is to compare MBCT intervention
versus a brief structured group psychoeducation. Our hypothesis is that MBCT will
be more effective in reducing the subsyndromal depressive symptoms and will
improve cognitive performance to a higher degree than the psychoeducational
treatment. It is also hypothesized that a significant increase of BDNF levels
will be found after the MBCT intervention. DISCUSSION: This is the first
randomized controlled trial to evaluate the effects of MBCT compared to an active
control group on depressive subthreshold depressive symptoms in patients with
bipolar disorder. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02133170. Registered
04/30/2014.
PMID- 25124513
TI - Validation of a laser-assisted wound measurement device in a wound healing model.
AB - In the treatment and monitoring of a diabetic or chronic wound, accurate and
repeatable measurement of the wound provides indispensable data for the patient's
medical record. This study aims to measure the accuracy of the laser-assisted
wound measurement (LAWM) device against traditional methods in the measurement of
area, depth and volume. We measured four 'healing' wounds in a Play-Doh((r))
based model over five subsequent states of wound healing progression in which the
model was irregularly filled in to replicate the healing process. We evaluated
the LAWM device against traditional methods including digital photograph
assessment with National Institutes of Health ImageJ software, measurements of
depth with a ruler and weight-to-volume assessment with dental paste. Statistical
analyses included analysis of variance (ANOVA) and paired t-tests. We demonstrate
that there are significantly different and nearly statistically significant
differences between traditional ruler depth measurement and LAWM device
measurement, but there are no statistically significant differences in area
measurement. Volume measurements were found to be significantly different in two
of the wounds. Rate of percentage change was analysed for volume and depth in the
wound healing model, and the LAWM device was not significantly different than the
traditional measurement technique. While occasionally inaccurate in its absolute
measurement, the LAWM device is a useful tool in the clinician's arsenal as it
reliably measures rate of percentage change in depth and volume and offers a
potentially aseptic alternative to traditional measurement techniques.
PMID- 25124514
TI - Sub-chronically exposing mice to a polycyclic aromatic hydrocarbon increases
lipid accumulation in their livers.
AB - The potential for exposing humans and wildlife to environmental polycyclic
aromatic hydrocarbons (PAHs) has increased. Risk assessments describing how PAHs
disturb lipid metabolism and induce hepatotoxicity have only received limited
attention. In the present study, seven-week-old male ICR mice received
intraperitoneal injections of 0, 0.01, 0.1 or 1mg/kg body weight 3
methylcholanthrene (3MC) per week for 10 weeks. A high-fat diet was provided
during the exposure. Histopathological lipid accumulation and lipid metabolism
related genes were measured. We observed that sub-chronic 3MC exposure
significantly increased lipid droplet and triacylglycerol (TG) levels in the
livers. A low dose of 3MC activated the aryl hydrocarbon receptor, which
negatively regulated lipid synthesis in the livers. The primary genes including
acetyl-CoA carboxylase (Acc), fatty acid synthase (Fas) and stearoyl-CoA
desaturase 1 (Scd1) decreased significantly when compared with those in the
control group, indicating that de novo fatty acid synthesis in the hepatocytes
was significantly inhibited by the sub-chronic 3MC exposure. However, the free
fatty acid (FFA) synthesis in the adipose tissue was greatly enhanced by up
regulating the expression of peroxisome proliferator-activated receptor gamma
(PPARgamma) and sterol regulatory element binding protein-1c (SREBP1C) and target
genes including Acc, Fas and Scd1. The synthesized FFA was released into the
blood and then transported into the liver by the up-regulation of Fat and Fatp2,
which resulted in the gradual accumulation of lipids in the liver. In conclusion,
histological examinations and molecular level analyses highlighted the
development of lipid accumulation and confirmed that 3MC significantly impaired
lipid metabolism in mice.
PMID- 25124515
TI - Investigation on the relationship between bioconcentration factor and
distribution coefficient based on class-based compounds: The factors that affect
bioconcentration.
AB - Bioconcentration factor (BCF) is one of the most important parameters in the
assessment of the potential hazard of new compounds in aquatic ecosystems.
However, the factors that influence the estimation of BCFs for a large variety of
chemicals have not been systemically investigated in the literature. In this
paper, a large BCF data set containing 1088 nonionic and ionic organic compounds
was used to study the relationship between BCF and molecular descriptors and
influencing factors. Step-by-step analysis on the class-based compounds showed
that nonlinear Gaussian and Sigmoid equations could well describe relationships
between logBCF and distribution coefficient for the compounds over a wide range
of structures and chloro or/and bromo substituted aromatics, respectively. The
quality of fit from the nonlinear models is better than the BCFBAF method from
the Epi Suite program for the class-based compounds. Systemic prediction
deviations have been observed for some types of compounds. The reasons for
systemic deviations for these compounds can be attributed to the difference in
bioconcentration mechanism for hydrophilic compounds, transformation for
hydroxyphenols and three-membered rings, physical barrier for long chain and
large polycyclic compounds, difference in determining methods of BCF (kinetic and
steady-state), bioavailability for highly hydrophobic compounds and accuracy of
BCF measurements for compounds with extremely high or low BCFs. These factors are
important and should be considered in any reliable bioconcentration prediction.
PMID- 25124516
TI - Filariasis asymptomatically infected donors have lower levels of disialylated IgG
compared to endemic normals.
AB - Helminths induce strong regulatory and T helper 2-type responses, whereby
antibody-derived host protection and regulation are essential components.
Lymphatic filariasis is an immune-mediated spectral disease that manifests as two
main clinical outcomes: chronic pathology or asymptomatic infection. These
outcomes depend on a multitude of factors, including parasite-induced
immunoregulation and host genetic background; antibody responses contribute to
this outcome. N-glycosylation of the Fc region of antibodies is a post
translational modification required for the structure and molecular function,
influencing host inflammatory and regulatory responses. Altered IgG glycosylation
correlates with disease, whereby decreased galactosylation is associated with
inflammation while increased sialylation is associated with anti-inflammatory
responses. We purified N-linked glycans from the Fc region of total IgG from
Wuchereria bancrofti-infected patients characterizing the two clinical
manifestations (chronic pathology and asymptomatic infection) and compared them
to infection-free endemic normals. Using capillary electrophoresis, we found that
there was no difference in galactosylation of total IgG between the three groups;
however, asymptomatically infected patients had significantly lower levels of
disialylated IgG compared to endemic normals and patients with pathology. These
data suggest that while galactosylation does not contribute to disease outcome,
sialylation may be involved in asymptomatic infection.
PMID- 25124517
TI - Identification of differential selection traces in two Polish cattle breeds.
AB - Genetic improvement of animals based on artificial selection is leading to
changes in the frequency of genes related to desirable production traits. The
changes are reflected by the neutral, intergenic single nucleotide polymorphims
(SNPs) being in long-range linkage disequilibrium with functional polymorphisms.
Genome-wide SNP analysis tools designed for cattle, allow for scanning
divergences in allelic frequencies between distinct breeds and thus for
identification of genomic regions which were divergently selected in breeds'
histories. In this study, by using Bovine SNP50 assay, we attempted to identify
genomic regions showing the highest differences in allele frequencies between two
distinct cattle breeds - preserved, unselected Polish Red breed and highly
selected Holstein cattle. Our study revealed 19 genomic regions encompassing 55
protein-coding genes and numerous quantitative trait loci which potentially may
underlie some of the phenotypic traits distinguishing the breeds.
PMID- 25124518
TI - Identification of a novel COL2A1 mutation (c.1744G>A) in a Japanese family: a
case report.
AB - INTRODUCTION: Mutations in the gene encoding the type II collagen gene (COL2A1)
have been found to affect the entire skeletal system. Recently, inheritable
skeletal dysplasia caused by novel COL2A1 mutations has been linked to an
inherited disease of the hip joint that neither involves the entire skeletal
system nor is characterized by the presence of concomitant disorders, such as
spinal or ocular abnormalities. CASE PRESENTATION: A 27-year-old Japanese woman
previously diagnosed with avasucular necrosis (AVN) of the femoral head on the
basis of radiological findings was referred to the study site for surgical
management of a painful hip joint. She had no history of disease but suffered
from bilateral hip joint lesions. Analysis of her pedigree revealed that
bilateral hip joint lesions affected more than three generations of her family.
Based on these findings, haplotype analysis of her and her family members was
performed by examining select candidate genes from the critical interval for
epiphyseal dysplasia of the femoral head on 12q13 and sequencing the promoter and
exonic regions of COL2A1. CONCLUSION: A novel COL2A1 mutation (c.1744G>A) was
identified within one Japanese family.
PMID- 25124519
TI - Neuroimmune biomarkers in schizophrenia.
AB - Schizophrenia is a heterogeneous psychiatric disorder with a broad spectrum of
clinical and biological manifestations. Due to the lack of objective tests, the
accurate diagnosis and selection of effective treatments for schizophrenia
remains challenging. Numerous technologies have been employed in search of
schizophrenia biomarkers. These studies have suggested that neuroinflammatory
processes may play a role in schizophrenia pathogenesis, at least in a subgroup
of patients. The evidence indicates alterations in both pro- and anti
inflammatory molecules in the central nervous system, which have also been found
in peripheral tissues and may correlate with schizophrenia symptoms. In line with
these findings, certain immunomodulatory interventions have shown beneficial
effects on psychotic symptoms in schizophrenia patients, in particular those with
distinct immune signatures. In this review, we evaluate these findings and their
potential for more targeted drug interventions and the development of companion
diagnostics. Although currently no validated markers exist for schizophrenia
patient stratification or the prediction of treatment efficacy, we propose that
utilisation of inflammatory markers for diagnostic and theranostic purposes may
lead to novel therapeutic approaches and deliver more effective care for
schizophrenia patients.
PMID- 25124520
TI - Cortical thinning and caudate abnormalities in first episode psychosis and their
association with clinical outcome.
AB - First episode psychosis (FEP) has been associated with structural brain changes,
largely identified by volumetric analyses. Advances in neuroimaging processing
have made it possible to measure geometric properties that may identify subtle
structural changes not appreciated by a measure of volume alone. In this study we
adopt complementary methods of assessing the structural integrity of grey matter
in FEP patients and assess whether these relate to patient clinical and
functional outcome at 3 year follow-up. 1.5 Tesla T1-weighted Magnetic Resonance
(MR) images were acquired for 46 patients experiencing their first episode of
psychosis and 46 healthy controls. Cerebral cortical thickness and local
gyrification index (LGI) were investigated using FreeSurfer software. Volume and
shape of the hippocampus, caudate and lateral ventricles were assessed using
manual tracing and spherical harmonics applied for shape description. A cluster
of cortical thinning was identified in FEP compared to controls; this was located
in the right superior temporal gyrus, sulcus, extended into the middle temporal
gyrus (lateral temporal cortex - LTC). Bilateral caudate volumes were
significantly lower in FEP relative to controls and the right caudate also
displayed regions of shape deflation in the FEP group. No significant structural
abnormalities were identified in cortical LGI or hippocampal or lateral ventricle
volume/shape. Neither LTC nor caudate abnormalities were related to change in
symptom severity or global functioning 3 years later. LTC and caudate
abnormalities are present at the first episode of psychosis but do not appear to
directly affect clinical or functional outcome.
PMID- 25124522
TI - A simplified procedure for gram-scale production of sialylglycopeptide (SGP) from
egg yolks and subsequent semi-synthesis of Man3GlcNAc oxazoline.
AB - Heterogeneity of glycan structures in native glycoconjugates always hampers
precise studies on carbohydrate-involved biological functions. To construct
homogeneous glycoconjugates from natural resource of homogeneous glycans is
therefore a practical approach to solve this problem. We report here an optimized
procedure for gram-scale production of sialylglycopeptide (SGP) containing a
disialyl biantennary complex-type N-glycan from egg yolks. Our new procedure
simplified the extraction process by treating the egg yolk powder with 40%
acetone, avoiding massive emulsification, high-speed centrifugation, and
sophisticated chromatography in reported methods. Subsequent semi-synthesis of
the N-glycan core Man3GlcNAc oxazoline from SGP was accomplished for the first
time via glyco-trimming and successive oxazoline formation. This efficient semi
synthesis provides an alternative to the pure chemical approach that involves
multi-step total synthesis and facilitates the application of endo-glycosidase
enabled chemoenzymatic synthesis of various homogeneous glycoconjugates.
PMID- 25124521
TI - Replication of previous genome-wide association studies of psychiatric diseases
in a large schizophrenia case-control sample from Spain.
AB - Genome wide association studies (GWAS) has allowed the discovery of some
interesting risk variants for schizophrenia (SCZ). However, this high-throughput
approach presents some limitations, being the most important the necessity of
highly restrictive statistical corrections as well as the loss of statistical
power inherent to the use of a Single Nucleotide Polymorphism (SNP) analysis
approach. These problems can be partially solved through the use of a polygenic
approach. We performed a genotyping study in SCZ using 86 previously associated
SNPs identified by GWAS of SCZ, bipolar disorder (BPD) and autistic spectrum
disorder (ASD) patients. The sample consisted of 3063 independent cases with DSM
IV-TR diagnosis of SCZ and 2847 independent controls of European origin from
Spain. A polygenic score analysis was also used to test the overall effect on the
SCZ status. One SNP, rs12290811, located in the ODZ4 gene reached statistical
significance (p=1.7*10(-4), Allelic odds ratio=1.21), a value very near to those
reported in previous GWAS of BPD patients. In addition, 4 SNPs were close to the
significant threshold: rs3850333, in the NRXN1 gene; rs6932590, at MHC;
rs2314398, located in an intergenic region on chromosome 2; and rs1006737, in the
CACNA1C gene. We also found that 74% of the studied SNPs showed the same tendency
(risk or protection alleles) previously reported in the original GWAS (p<0.001).
Our data strengthen the polygenic component of susceptibility to SCZ. Our
findings show ODZ4 as a risk gene for SCZ, emphasizing the existence of common
vulnerability in psychosis.
PMID- 25124523
TI - Otolaryngology--head and neck surgery in undergraduate medical education:
advances and innovations.
AB - OBJECTIVES/HYPOTHESIS: Medical students graduate with the knowledge and skills to
be undifferentiated general physicians. Otolaryngology-head and neck surgery
(OtoHNS) is an essential component of primary healthcare, but is
disproportionately under-represented in undergraduate medical education (UME).
Advances and innovations in educational technology may represent an exciting and
creative solution to this important problem. Failure to meet this educational
need will result in substantial downstream effects in primary healthcare
delivery. The objectives of this study were to 1) demonstrate current deficits in
OtoHNS teaching at the UME level; 2) develop, validate, and critically appraise
educational innovations that may enrich OtoHNS teaching in medical school
curricula; and 3) propose a process for standardization of learning objectives
for OtoHNS in UME as it relates to development and deployment of such educational
tools. STUDY DESIGN: A white paper, prepared as a Triological Society thesis,
which consolidates a prospective 10-year investigation of the problem of and
potential solutions for under-representation of OtoHNS in UME. Cited datasets
include multicenter surveys, cohort studies, and prospective, randomized
controlled trials. METHODS: A series of published and unpublished data were
synthesized that addresses the following: 1) the current state of OtoHNS teaching
at the UME level with respect to content, volume, structure, and methods; and 2)
educational innovations including e-learning and simulation with emphasis on
validity and learning effectiveness. Educational innovations specific to
postgraduate (residency) training were excluded. RESULTS: Data support the
observation that there is uniformly disproportionate under-representation of
OtoHNS within UME curricula. Medical school graduates, especially those pursuing
primary care specialties, report poor overall comfort levels in managing OtoHNS
problems. A series of novel teaching methods were developed and validated using e
learning and simulation. Selected technologies may have a role in medical student
teaching. It has been shown that e-learning has limited value in teaching complex
spatial anatomy to novice learners, but good value in teaching basic clinical
knowledge and selected technical skills. The role of simulation as it pertains to
the novice learner is evolving. Important factors to consider during development
of these tools include: 1) knowledge base and learning style of the learner, 2)
complexity and nature of the learning objectives, 3) understanding the features
and limitations of different technological genres, and 4) a team approach to
module development. There remains a role for traditional teaching paradigms such
as lectures, labs, and standardized patients; however, the choice of
instructional genre should be fundamentally tailored to the nature of the
learning outcomes. CONCLUSIONS: Enriching OtoHNS teaching in medical school is
essential optimize primary care delivered to patients. Although e-learning and
simulation are broadly accepted and desirable by today's medical students, these
technologies should be woven into the fabric of UME pedagogical principles
judiciously, and only after empiric assessment. Foundational to the development
and implementation of these technologies is the framework of standardized
competency-based learning objectives, common to all graduating medical students.
LEVEL OF EVIDENCE: NA
PMID- 25124524
TI - Effects of serial and concurrent training on acquisition and generalization.
AB - Despite a large body of research demonstrating that generalization to novel
stimuli can be produced by training sufficient exemplars, the methods by which
exemplars can be trained remain unclear. The purpose of the current study was to
evaluate 2 methods, serial and concurrent presentation of stimuli, to train
sufficient exemplars. Five preschool children with developmental delays were
taught to identify letters or letter sounds using serial and concurrent
presentation. Generalization to untrained exemplars was evaluated for targets
trained using each method. Participants reached the mastery criterion in fewer
training sessions, on average, using the concurrent method of presentation than
the serial method, and the concurrent method also resulted in greater
generalization to untrained exemplars.
PMID- 25124526
TI - Should we adjust for a confounder if empirical and theoretical criteria yield
contradictory results? A simulation study.
AB - Confounders can be identified by one of two main strategies: empirical or
theoretical. Although confounder identification strategies that combine empirical
and theoretical strategies have been proposed, the need for adjustment remains
unclear if the empirical and theoretical criteria yield contradictory results due
to random error. We simulated several scenarios to mimic either the presence or
the absence of a confounding effect and tested the accuracy of the exposure
outcome association estimates with and without adjustment. Various criteria
(significance criterion, Change-in-estimate(CIE) criterion with a 10% cutoff and
with a simulated cutoff) were imposed, and a range of sample sizes were trialed.
In the presence of a true confounding effect, unbiased estimates were obtained
only by using the CIE criterion with a simulated cutoff. In the absence of a
confounding effect, all criteria performed well regardless of adjustment. When
the confounding factor was affected by both exposure and outcome, all criteria
yielded accurate estimates without adjustment, but the adjusted estimates were
biased. To conclude, theoretical confounders should be adjusted for regardless of
the empirical evidence found. The adjustment for factors that do not have a
confounding effect minimally effects. Potential confounders affected by both
exposure and outcome should not be adjusted for.
PMID- 25124527
TI - Pentacoordinate phosphorus in a high-pressure polymorph of phosphorus nitride
imide P4N6(NH).
AB - Coordination numbers higher than usual are often associated with superior
mechanical properties. In this contribution we report on the synthesis of the
high-pressure polymorph of highly condensed phosphorus nitride imide P4 N6 (NH)
representing a new framework topology. This is the first example of phosphorus in
trigonal-bipyramidal coordination being observed in an inorganic network
structure. We were able to obtain single crystals and bulk samples of the
compound employing the multi-anvil technique. gamma-P4 N6 (NH) has been
thoroughly characterized using X-ray diffraction, solid-state NMR and FTIR
spectroscopy. The synthesis of gamma-P4 N6 (NH) gives new insights into the
coordination chemistry of phosphorus at high pressures. The synthesis of further
high-pressure phases with higher coordination numbers exhibiting intriguing
physical properties seems within reach.
PMID- 25124525
TI - Maternal periconceptional occupational pesticide exposure and neural tube
defects.
AB - BACKGROUND: Adverse associations between maternal pesticide exposure and neural
tube defects (NTDs) have been suggested but not consistently observed. This study
used data from the multisite National Birth Defects Prevention Study to examine
associations between maternal periconceptional (1 month preconception through 2
months postconception) occupational pesticide exposure and NTDs. METHODS: Mothers
of 502 NTD cases and 2950 unaffected live-born control infants with estimated
delivery dates from 1997 through 2002 were included. Duration, categorical
intensity scores, and categorical frequency scores for pesticide classes (e.g.,
insecticides) were assigned using a modified, literature-based job-exposure
matrix and maternal-reported occupational histories. Adjusted odds ratios (aORs)
and 95% confidence intervals were estimated based on fitted multivariable
logistic regression models that described associations between maternal
periconceptional occupational pesticide exposure and NTDs. The aORs were
estimated for pesticide exposure (any [yes/no] and cumulative exposure [intensity
* frequency * duration] to any pesticide class, each pesticide class, or
combination of pesticide classes) and all NTD cases combined and NTD subtypes.
RESULTS: Positive, but marginally significant or nonsignificant, aORs were
observed for exposure to insecticides + herbicides for all NTD cases combined and
for spina bifida alone. Similarly, positive aORs were observed for any exposure
and cumulative exposure to insecticides + herbicides + fungicides and anencephaly
alone and encephalocele alone. All other aORs were near unity. CONCLUSION:
Pesticide exposure associations varied by NTD subtype and pesticide class.
Several aORs were increased, but not significantly. Future work should continue
to examine associations between pesticide classes and NTD subtypes using a
detailed occupational pesticide exposure assessment and examine pesticide
exposures outside the workplace.
PMID- 25124528
TI - Cost-effectiveness of using small vertebrates as indicators of disturbance.
AB - In species-rich tropical forests, effective biodiversity management demands
measures of progress, yet budgetary limitations typically constrain capacity of
decision makers to assess response of biological communities to habitat change.
One approach is to identify ecological-disturbance indicator species (EDIS) whose
monitoring is also monetarily cost-effective. These species can be identified by
determining individual species' responses to disturbance across a gradient;
however, such responses may be confounded by factors other than disturbance. For
example, in mountain environments the effects of anthropogenic habitat alteration
are commonly confounded by elevation. EDIS have been identified with the
indicator value (IndVal) metric, but there are weaknesses in the application of
this approach in complex montane systems. We surveyed birds, small mammals, bats,
and leaf-litter lizards in differentially disturbed cloud forest of the
Ecuadorian Andes. We then incorporated elevation in generalized linear (mixed)
models (GL(M)M) to screen for EDIS in the data set. Finally, we used rarefaction
of species accumulation data to compare relative monetary costs of identifying
and monitoring EDIS at equal sampling effort, based on species richness. Our
GL(M)M generated greater numbers of EDIS but fewer characteristic species
relative to IndVal. In absolute terms birds were the most cost-effective of the 4
taxa surveyed. We found one low-cost bird EDIS. In terms of the number of
indicators generated as a proportion of species richness, EDIS of small mammals
were the most cost-effective. Our approach has the potential to be a useful tool
for facilitating more sustainable management of Andean forest systems.
PMID- 25124529
TI - Comparison of sub-bandage pressures achieved by 3 abdominal bandaging techniques
in horses.
AB - REASONS FOR PERFORMING STUDY: Clinicians frequently place post operative
abdominal bandages on horses undergoing laparotomies. Presently, no information
exists on the amount of incisional support provided by these bandages.
Determination of sub-bandage pressure provides a means of comparing the ability
of different bandages to support incisions. OBJECTIVES: Determination of sub
bandage pressure over a 24 h period using 3 bandaging techniques. STUDY DESIGN: A
randomised, crossover design using 9 healthy horses. METHODS: Horses were
randomly assigned to a treatment regimen consisting of placement of 3 abdominal
bandage types, namely an elastic bandage (ELA), the CM(TM) Hernia Heal Belt (CM)
or a nylon binder (NYL). The sub-bandage pressures for each bandage were measured
with the Picopress(r) compression-measuring system at 0, 2, 4, 6, 8, 12, 16, 20
and 24 h after application. RESULTS: No time and treatment interactions were
observed, and bandage pressures were maintained within each treatment group over
the 24 h period. Mean sub-bandage pressures were different between all treatment
groups (P < 0.001) at 39 (95% confidence interval, 36.7-40.5 mmHg), 25 (95%
confidence interval, 23.9-27.7 mmHg) and 5 mmHg (95% confidence interval, 4.1-7.8
mmHg) for CM, ELA and NYL bandages, respectively. Horses were more likely to lie
down with the CM (P = 0.02) and ELA treatments (P = 0.0002) when compared with
the NYL treatment. The ELA bandages were more likely to displace caudally
compared with both CM and NYL bandages. CONCLUSIONS: The CM bandage was superior
to both ELA and NYL bandages with regard to measured sub-bandage pressure over
the 24 h period. The clinical significance of the differences in sub-bandage
pressure between treatments cannot be determined by this study.
PMID- 25124530
TI - Hedonic tone is associated with left supero-lateral medial forebrain bundle
microstructure.
AB - BACKGROUND: The medial forebrain bundle (MFB) is an important pathway of the
reward system. Two branches have been described using diffusion magnetic
resonance imaging (MRI)-based tractography: the infero-medial MFB (imMFB) and the
supero-lateral MFB (slMFB). Previous studies point to white-matter
microstructural alterations of the slMFB in major depressive disorder (MDD)
during acute episodes. To extend this finding, this study investigates whether
white-matter microstructure is also altered in MDD patients that are in
remission. Further, we explore associations between diffusion MRI-based metrics
of white-matter microstructure of imMFB, slMFB and hedonic tone, the ability to
derive pleasure. METHOD: Eighteen remitted depressed (RD) and 22 never depressed
(ND) participants underwent high angular resolution diffusion-weighted imaging
(HARDI) scans. To reconstruct the two pathways of the MFB (imMFB and slMFB) we
used the damped Richardson-Lucy (dRL) algorithm. Mean fractional anisotropy (FA)
was sampled along the tracts. RESULTS: Mean FA of imMFB, slMFB and a comparison
tract (the middle cerebellar peduncle) did not differ between ND and RD
participants. Hedonic capacity correlated negatively with mean FA of the left
slMFB, explaining 21% of the variance. CONCLUSIONS: Diffusion MRI-based metrics
of white-matter microstructure of the MFB in RD do not differ from ND. Hedonic
capacity is associated with altered white-matter microstructure of the slMFB.
PMID- 25124531
TI - Microstructural trabecular bone from patients with osteoporotic hip fracture or
osteoarthritis: its relationship with bone mineral density and bone remodelling
markers.
AB - Osteoporosis (OP) and osteoarthritis (OA) are the most prevalent musculoskeletal
disorders in the elderly but the relationship between them is unclear. The
purposes of this study are to analyze the bone turnover markers (BTM), bone
mineral density (BMD) and the structural and mechanical properties of trabecular
bone in patients with OP and OA, and to explore the relationship between these
two diseases. We studied 12 OP patients and 13 OA patients. We analyzed BTM (beta
CrossLaps and PINP), BMD and microstructural and biomechanical parameters (micro
CT). Our results were: OP group has higher levels of beta-CrossLaps and lower BMD
at the femoral neck. Also, OP patients have a decreased volume of trabecular bone
and less trabecular number, with architecture showing prevalence of rod-like
trabeculae and worse connectivity than OA patients. The biomechanical parameters
were worse in OP patients. BMD was correlated with almost all the structural and
biomechanical parameters. Moreover, beta-CrossLaps was negatively correlated with
hip BMD and with bone surface density and positively with trabecular separation.
BTM, BMD and bone microstructural changes in osteoporosis are opposite to those
of OA. These findings justify a less resistant bone with higher risk of fragility
fractures in OP patients. These histomorphometric and biomechanical changes may
be suspected by measuring of BMD and beta-CrossLaps levels.
PMID- 25124532
TI - Use of FRAX(r)-based fracture risk assessments to identify patients who will
benefit from osteoporosis therapy.
AB - Several pharmacological interventions, including selective estrogen receptor
modulators (SERMs), bisphosphonates, denosumab, and strontium ranelate have
demonstrated efficacy in reducing the incidence of osteoporotic fractures, the
most severe consequence of postmenopausal osteoporosis. Until recently, bone
mineral density (BMD) was the primary factor used to determine which
postmenopausal women may require osteoporosis treatment. However, clinical
guidelines now recommend the use of the Fracture Risk Assessment Tool
(FRAX((r))), a computer-based algorithm introduced by the World Health
Organization, to help primary care physicians identify postmenopausal women who
may be candidates for pharmacological osteoporosis therapy based on the level of
fracture risk. Beyond its utility as a resource for determining whether or not to
initiate osteoporosis treatment, clinical studies have begun to evaluate the
correlation between FRAX((r))-based 10-year fracture probability and efficacy of
different osteoporosis treatments. Bazedoxifene, clodronate, and denosumab have
shown greater fracture risk reduction at higher FRAX((r))-based 10-year fracture
probabilities, but the efficacy of raloxifene, alendronate, and strontium
ranelate were relatively stable regardless of fracture probability. In summary,
these data suggest that the relationship between FRAX((r))-based fracture
probability and efficacy of different osteoporosis treatments varies depending
upon the agent in question.
PMID- 25124533
TI - Mass spectrometry based quantitative proteomics and integrative network analysis
accentuates modulating roles of annexin-1 in mammary tumorigenesis.
AB - Annexin-1 (ANXA1) is known to be involved in important cellular processes and
implicated in cancer. Our previous study showed its roles in cell migration and
DNA-damage response processes in breast cancer initiation. In order to understand
its roles in tumorigenesis, we extended our studies to analyze tumors derived
from polyomavirus middle T-antigen ANXA1 heterozygous (ANXA1(+/-) ) and ANXA1
null (ANXA1(-/-) ) mice. We performed quantitative comparison of ANXA1(+/-) and
ANXA1(-/-) tumors employing reductive dimethyl labeling quantitative proteomics.
We observed 253 differentially expressed proteins (DEPs) with high statistical
significance among over 5000 quantified proteins. Combinatorial use of pathway
and network-based computational analyses of the DEPs revealed that ANXA1
primarily modulates processes related to cytoskeletal remodeling and immune
responses in these mammary tumors. Of particular note, ANXA1(-/-) tumor showed
reduced expression of a known epithelial-to-mesenchymal transition (EMT) marker
vimentin, as well as myosin light-chain kinase, which has been reported to induce
Rho-kinase mediated assembly of stress fibers known to be implicated in EMT.
Integrative network analysis of established interactome of ANXA1 alongside with
DEPs further highlights the involvement of ANXA1 in EMT. Functional role of ANXA1
in tumorigenesis was established in invasion assay where knocking down ANXA1 in
murine mammary tumor cell line 168FARN showed lower invasive capability.
Altogether, this study emphasizes that ANXA1 plays modulating roles contributing
to invasion-metastasis in mammary tumorigenesis, distinctive to its roles in
cancer initiation.
PMID- 25124534
TI - Self-excising integrative yeast plasmid vectors containing an intronated
recombinase gene.
AB - Site-specific recombinases are widely used for selectable marker recycling in
molecular-genetic manipulations with eukaryotic cells. This usually involves the
use of two genetic constructs, one of which possesses a selectable marker flanked
by the recombinase recognition sequences, while the other one bears the
recombinase gene. Combining the recombinase gene with its recognition sequences
in one plasmid is usually avoided, as it may lead to undesirable recombination
due to promoter leakage, while the plasmid is maintained in Escherichia coli
cells. Here, we describe yeast vectors possessing Cre recombinase genes under
control of regulatable yeast promoters and loxP sequences for the in vivo vector
backbone excision. The plasmid stability in E. coli is ensured by the presence of
an intron in the recombinase gene. Applicability of these vectors was validated
by disruptions of the Hansenula polymorpha PMC1 and Saccharomyces cerevisiae
HSP104 and PRB1 genes.
PMID- 25124536
TI - Hooked on UVR.
PMID- 25124535
TI - Impact of high-sensitivity Troponin T on hospital admission, resources
utilization, and outcomes.
AB - AIMS: The use of high-sensitivity cardiac Troponin T (hs-cTnT) assay might lead
to overdiagnosis and overtreatment of Acute Coronary Syndromes (ACS). This study
assessed the epidemiological, clinical and prognostic impact of introducing hs
cTnT in the everyday clinical practice of an Emergency Department. METHODS AND
RESULTS: We compared all consecutive patients presenting with suspected ACS at
the Emergency Department, for whom troponin levels were measured. In particular,
we considered 597 patients presenting during March 2010, when standard cardiac
Troponin T (cTnT) assay was used, and 629 patients presenting during March 2011,
when hs-cTnT test was used. Patients with suspected ACS and troponin levels above
the 99th percentile (Upper Reference Limit, URL) significantly increased when
using an hs-cTnT assay (17.2% vs. 37.4%, p< 0.001). Accordingly, also the mean
GRACE risk score increased (124.2 +/- 37.2 vs. 136.7 +/- 32.2; p< 0.001).
However, the final diagnosis of Acute Myocardial Infarction (AMI) did not change
significantly (8.7% vs. 6.8%, p=0.263) by using a rising and/or falling pattern
of hs-cTnT (change >= 50% or >= 20% depending on baseline values). In addition,
no significant differences were found between the two study groups with respect
to in-hospital (2.7% vs. 1.9%, p=0.366) and 1-year mortality (9.8% vs. 7.6%,
p=0.216). CONCLUSIONS: We did not observe overdiagnosis and overtreatment issues
in presenters with suspected ACS managed by appropriate changes in hs-cTnT
levels, despite the increase in the number of patients presenting with abnormal
troponin levels. This occurred without a rise in short-term and mid-term
mortality.
PMID- 25124542
TI - Antibody response to dengue virus.
AB - In this review, we discuss the current knowledge of the role of the antibody
response against dengue virus and highlight novel insights into targets
recognized by the human antibody response. We also discuss how the balance of
pathological and protective antibody responses in the host critically influences
clinical aspects of the disease.
PMID- 25124540
TI - IFN-gamma and TNF associated with severe falciparum malaria infection in Saudi
pregnant women.
AB - BACKGROUND: Tumour necrosis factor (TNF) and interferon gamma (IFN-gamma),
encoded by TNF-836 C/A (rs 1800630) and IFN-gamma -1616 C/T (rs2069705) genes,
are key immunological mediators that are believed to both play protective and
pathological roles in malaria. The aim of this study was to investigate the
relationship between TNF-836 C/A and IFN-gamma-1616 C/T polymorphism and
susceptibility to severe malaria in pregnant women. METHODS: A prospective cohort
(cross-sectional) study was conducted in pregnant women attending the out-patient
clinic in King Fahad Specialist Hospital in Jazan (KFSHJ), with a clinical
diagnosis of malaria. A total of one hundred and eighty six pregnant women were
genotyped for single nucleotide polymorphism (SNP) for TNF and IFN-gamma using
Taqman(r) MGB Probes. Serum cytokine concentrations were measured by sandwich
ELISA method. RESULTS: A hospital case-control study of severe malaria in a Saudi
population identified strong associations with individual single-nucleotide
polymorphisms in the TNF and IFN-gamma genes, and defined TNF-836 C and IFN-gamma
1616 T genotypes and alleles which were statistically significantly associated
with severe malaria infection. Furthermore, TNF-836 CC and IFN-gamma-1616 TT
genotypes were associated with higher serum concentration of TNF and IFN-gamma,
respectively, and with susceptibility to severe malaria. CONCLUSIONS: This data
provides a starting point for functional and genetic analysis of the TNF and IFN
gamma genomic region in malaria infection affecting Saudi populations.
PMID- 25124541
TI - Efficacy and safety of canagliflozin in subjects with type 2 diabetes: systematic
review and meta-analysis.
AB - PURPOSE: To assess the efficacy and safety of the novel sodium glucose co
transporter 2 (SGLT2) inhibitor-canagliflozin for type 2 diabetes (T2DM).
METHODS: A search of Medline (1946-January 2014), Embase (1950-January 2014), and
The Cochrane Library for randomized controlled trials of canagliflozin compared
to placebo or active comparator in T2DM was performed. Clinical Trials website
and unpublished U.S. Food and Drug Administration data were also searched.
RESULTS: Ten trials including 6,701 patients were analyzed. Compared with
placebo, canagliflozin produced absolute reductions in glycated hemoglobin A1c
levels when used as monotherapy (weighted mean difference (WMD) -1.08%, 95%
confidence interval (CI) [-1.25 to -0.90], p < 0.00001) or add-on treatment (WMD
0.73%, 95%CI [-0.84 to -0.61], p < 0.00001). When compared with other active
comparators, canagliflozin significantly reduced HbA1c by -0.21% (WMD, 95%CI [
0.33 to -0.08], p = 0.001). Canagliflozin led to greater body weight loss (vs.
placebo, WMD -2.81 kg, 95%CI [-3.26 to -2.37]; vs. active comparators, WMD -3.49
kg, 95%CI [-4.86 to -2.12]). Hypoglycemia with canagliflozin was similar to
placebo or sitagliptin, and was lower than glimepiride (risk ratio (RR) 0.15,
95%CI [0.10 to 0.22]). Genital tract infections were more common with
canagliflozin (vs. placebo, RR 3.76, 95%CI [2.23 to 6.35]; vs. active
comparators, RR 4.95, 95%CI [3.25 to 7.52]). Similar incidences of urinary tract
infections were noted with canagliflozin compared with control groups.
CONCLUSION: Canagliflozin led to improvements in reducing glycated hemoglobin A1c
levels and body weight with low risk of hypoglycemia in patients with T2DM.
Common adverse effects including genital tract infections and osmotic diuresis
related AEs were identified and reviewed. Risks of cardiovascular events are even
less certain, and more data on long-term effects are needed.
PMID- 25124543
TI - Flatland goes 3D.
PMID- 25124545
TI - Manifold learning based ECG-free free-breathing cardiac CINE MRI.
AB - PURPOSE: To present and validate a manifold learning (ML)-based method that can
estimate both cardiac and respiratory navigator signals from electrocardiogram
(ECG)-free free-breathing cardiac magnetic resonance imaging (MRI) data to
achieve self-gated retrospective CINE reconstruction. MATERIALS AND METHODS: In
this work the use of the ML method is demonstrated for 2D cardiac CINE to achieve
both cardiac and respiratory self-gating without the need of an external
navigator or ECG signal. This is achieved by sequentially applying ML to two sets
of retrospectively reconstructed real-time images with differing temporal
resolutions. A 1D cardiac signal is estimated by applying ML to high temporal
resolution real-time images reconstructed from the acquired data. Using the
estimated cardiac signal, a 1D respiratory signal was obtained by applying the ML
method to low temporal resolution images reconstructed from the same acquired
data for each cardiac cycle. Data were acquired in five volunteers with a 2D
golden angle radial trajectory in a balanced steady-state free precession (b
SSFP) acquisition. The accuracy of the estimated cardiac signal was calculated as
the standard deviation of the temporal difference between the estimated signal
and the recorded ECG. The correlation between the estimated respiratory signal
and standard pencil beam navigator signal was evaluated. Gated CINE
reconstructions (20 cardiac phases per cycle, temporal resolution ~30 msec) using
the estimated cardiac and respiratory signals were qualitatively compared against
conventional ECG-gated breath-hold CINE acquisitions. RESULTS: Accurate cardiac
signals were estimated with the proposed method, with an error standard deviation
in comparison to ECG lower than 20 msec. Respiratory signals estimated with the
proposed method achieved a mean cross-correlation of 94% with respect to standard
pencil beam navigator signals. Good quality visual scores of 2.80 +/- 0.45
(scores from 0, bad, to 4, excellent quality) were observed for the proposed
approach in comparison with the conventional ECG-gated breath-hold images (visual
score: 3.00 +/- 0.71). CONCLUSION: Accurate respiratory and cardiac navigator
signals can be estimated using the proposed framework from the acquired data
itself, resulting in retrospective self-gated CINE reconstruction with high
spatial and temporal quality.
PMID- 25124544
TI - Prophylactic effect of human lactoferrin against Streptococcus mutans bacteremia
in lactoferrin knockout mice.
AB - Streptococcus mutans is the primary agent of dental caries, which is often
detected in transient bacteremia. Lactoferrin is a multifunctional glycoprotein
showing antibacterial activities against several Streptococcus species. We
reported here the prophylactic effect of human lactoferrin (hLF) in a lactoferrin
knockout mouse (LFKO-/-) bacteremic model. The hLF treatment significantly
cleared S. mutans from the blood and organs of bacteremic mice when compared to
the non-hLF treated mice. Further, analysis of serum cytokines, spleen and liver
cytokine mRNA levels revealed that hLF prophylaxis modulates their release
differently when compared to the non-hLF treated group. C-reactive protein level
(P = 0.003) also decreased following hLF prophylaxis in S. mutans induced
bacteremic mice. Additional quantitative RT-PCR analysis revealed that hLF
prophylaxis significantly decreased the expression level of IFN-gamma, TNF-alpha,
IL-1beta, IL-6, MPO and iNOS in spleen and liver. These results suggested that
the hLF protects the host against S. mutans-induced experimental bacteremia.
PMID- 25124546
TI - Segmental uniparental isodisomy of chromosome 6 causing transient diabetes
mellitus and merosin-deficient congenital muscular dystrophy.
AB - Segmental uniparental isodisomy (iUPD) is a rare genetic event that may cause
aberrant expression of imprinted genes, and reduction to homozygosity of a
recessive mutation. Transient neonatal diabetes mellitus (TNDM) is typically
caused by imprinting aberrations in chromosome 6q24 TNDM differentially
methylated region (DMR). Approximately, 15.12 Mb upstream in 6q22-q23 is located
LAMA2, the gene responsible of merosin-deficient congenital muscular dystrophy
type 1A (MDC1A). We investigated a patient diagnosed both with TNDM and MDC1A,
born from a twin dichorionic discordant pregnancy. Parents are first-degree
cousins. Methylation sensitive-PCR of the imprinted 6q24 TNDM CpG island showed
only the non-methylated (paternal) allele. Microsatellite markers and SNP array
profiling disclosed normal biparental inheritance at 6p and a segmental paternal
iUPD, between 6q22.33 and 6q27. Sequencing of LAMA2 exons showed a homozygous
frameshift mutation, c.7490_7493dupAAGA, which predicts p.Asp2498GlufsX4, in exon
54. Her father, but not her mother, was a carrier of the mutation. While
segmental paternal iUPD6 causing TNDM was reported twice, there are no previous
reports of MDC1A caused by this event. This is a child with two genetic
disorders, yet neither is caused by the parental consanguinity, which reinforces
the importance of considering different etiological mechanisms in the genetic
clinic.
PMID- 25124547
TI - Retrospective data analysis and proposal of a practical acceptance criterion for
inter-laboratory cross-validation of bioanalytical methods using liquid
chromatography/tandem mass spectrometry.
AB - The purpose of this study is to conduct a retrospective data analysis for inter
laboratory cross-validation studies to set a reasonable and practical acceptance
criterion based on a number of cross-validation results. From the results of
cross-validation studies for 16 compounds and their metabolites, analytical bias
and variation were evaluated. The accuracy of cross-validation samples was
compared with that of quality control (QC) samples with statistical comparison of
the analytical variation. An acceptance criterion was derived with a confidential
interval approach. As the results, while a larger bias was observed for the cross
validation samples, the bias was not fully caused by analytical variation or bias
attributable to the analytical methods. The direction of the deviation between
the cross-validation samples and QC samples was random and not concentration
dependent, suggesting that inter-laboratory variability such as preparation
errors could be a source of bias. A derived acceptance criterion corresponds to
one prescribed in the Guideline on bioanalytical method validation from the
Ministry of Health, Labour and Welfare in Japan and is a little wider than one in
the European Medical Agency. In conclusion, thorough retrospective data analysis
revealed potential causes of larger analytical bias in inter-laboratory cross
validation studies. A derived acceptance criterion would be practical and
reasonable for the inter-laboratory cross-validation study.
PMID- 25124548
TI - Behavioral extremes of trait anxiety in mice are characterized by distinct
metabolic profiles.
AB - No comprehensive metabolic profile of trait anxiety is to date available. To
identify metabolic biosignatures for different anxiety states, we compared mice
selectively inbred for ~ 40 generations for high (HAB), normal (NAB) or low (LAB)
anxiety-related behavior. Using a mass spectrometry-based targeted metabolomics
approach, we quantified the levels of 257 unique metabolites in the cingulate
cortex and plasma of HAB, NAB and LAB mice. We then pinpointed affected molecular
systems in anxiety-related behavior by an in silico pathway and network
prediction analysis followed by validation of in silico predicted alterations
with molecular assays. We found distinct metabolic profiles for different trait
anxiety states and detected metabolites with altered levels both in cingulate
cortex and plasma. Metabolomics data revealed common candidate biomarkers in
cingulate cortex and plasma for anxiety traits and in silico pathway analysis
implicated amino acid metabolism, pyruvate metabolism, oxidative stress and
apoptosis in the regulation of anxiety-related behavior. We report characteristic
biosignatures for trait anxiety states and provide a network map of pathways
involved in anxiety-related behavior. Pharmacological targeting of these pathways
will enable a mechanism-based approach for identifying novel therapeutic targets
for anxiety disorders.
PMID- 25124549
TI - Suicide in children and young adolescents: a 25-year database on suicides from
Northern Finland.
AB - Despite the large amount of research on adolescent suicidality, there are few
detailed studies illustrating the characteristics of child and adolescent
completed suicide. Our study presents the characteristics of child and adolescent
suicides occurring over a period of 25 years within a large geographical area in
Northern Finland, with a special focus on gender differences. The study sample
included all 58 suicides among children and adolescents (<18 years) occurring in
the province of Oulu in Finland between 1988 and 2012. The data is based on
documents pertaining to establish the cause of death from forensic autopsy
investigations. A register linkage to the data from the Finnish Hospital
Discharge Register (FHDR) was also made. 79% of the suicide victims were male.
Violent suicide methods predominated in both genders (males 98%, females 83%).
While symptoms of mental illness were common, only a minority (15% of males and
17% of females) had a previous history of psychiatric hospitalization. 17% of
females but none of the males had been hospitalized previously due to self
poisoning. A greater proportion of females than males had a history of self
cutting (33% vs. 7%) and previous suicide attempts (25% vs. 4%). 48% of males and
58% of females were under the influence of alcohol at the time of their suicide,
and alcohol intoxication was related to suicides during the night. One fifth of
the adolescents screened positive for substances other than alcohol. The results
of this study indicate that there are similarities but also some differences in
the characteristics of male and female suicides in adolescents.
PMID- 25124550
TI - Zolpidem and the risk of Parkinson's disease: a nationwide population-based
study.
AB - BACKGROUND: This nationwide population-based study investigated the risk of
Parkinson's disease (PD) after zolpidem use in patients with sleep disturbance
using the National Health Insurance Research Database (NHIRD) in Taiwan. MATERIAL
AND METHODS: In total, 59,548 adult patients newly diagnosed with sleep
disturbance and who used zolpidem were recruited as the study cohort, along with
42,171 subjects who did not use zolpidem as a comparison cohort from 2002 to
2009. Each patient was monitored for 5 years, and those who subsequently had PD
were identified. A Cox proportional hazards model was used to compare the risk of
PD between the study and comparison cohorts after adjusting for possible
confounding risk factors. RESULTS: The patients who received zolpidem had a
higher cumulative rate of PD than those who did not receive zolpidem during the 5
year follow-up period (1.2% vs. 0.5%, P < 0.001). The adjusted hazard ratios were
1.10 (95% CI, 0.88-1.37), 1.41 (95% CI, 1.17-1.72), and 1.27 (95% CI, 1.05-1.55)
for zolpidem use with 28-90, 91-365, and more than 365 cumulative defined daily
doses (cDDDs), respectively, compared to those who did not use zolpidem.
CONCLUSIONS: Among the patients with sleep disturbance, zolpidem use increased
the risk of PD after 5 years of follow-up. Further mechanistic research of
zolpidem effect in PD is needed.
PMID- 25124551
TI - Real-time in vivo periprostatic nerve tracking using multiphoton microscopy in a
rat survival surgery model: a promising pre-clinical study for enhanced nerve
sparing surgery.
AB - OBJECTIVES: To assess the ability of multiphoton microscopy (MPM) to visualise,
differentiate and track periprostatic nerves in an in vivo rat model, mimicking
real-time imaging in humans during RP and to investigate the tissue toxicity and
reproducibility of in vivo MPM on prostatic glands in the rat after imaging and
final histological correlation study. MATERIALS AND METHODS: In vivo prostatic
rat imaging was carried out using a custom-built bench-top MPM system generating
real-time three-dimensional histological images, after performing survival
surgery consisting of mini-laparotomies under xylazine/ketamine anaesthesia
exteriorising the right prostatic lobe. The acquisition time and the depth of
anaesthesia were adjusted for collecting multiple images in order to track the
periprostatic nerves in real-time. The rats were then monitored for 15 days
before undergoing a new set of imaging under similar settings. After humanely
killing the rats, their prostates were submitted for routine histology and
correlation studies. RESULTS: In vivo MPM images distinguished periprostatic
nerves within the capsule and the prostatic glands from fresh unprocessed
prostatic tissue without the use of exogenous contrast agents or biopsy sample.
Real-time nerve tracking outlining the prostate was feasible and acquisition was
not disturbed by motion artefacts. No serious adverse event was reported during
rat monitoring; no tissue damage due to laser was seen on the imaged lobe
compared with the contralateral lobe (control) allowing comparison of their
corresponding histology. CONCLUSIONS: For the first time, we have shown that in
vivo tracking of periprostatic nerves using MPM is feasible in a rat model.
Development of a multiphoton endoscope for intraoperative use in humans is
currently in progress and must be assessed.
PMID- 25124552
TI - Comparative genomics highlights the unique biology of Methanomassiliicoccales, a
Thermoplasmatales-related seventh order of methanogenic archaea that encodes
pyrrolysine.
AB - BACKGROUND: A seventh order of methanogens, the Methanomassiliicoccales, has been
identified in diverse anaerobic environments including the gastrointestinal
tracts (GIT) of humans and other animals and may contribute significantly to
methane emission and global warming. Methanomassiliicoccales are phylogenetically
distant from all other orders of methanogens and belong to a large evolutionary
branch composed by lineages of non-methanogenic archaea such as
Thermoplasmatales, the Deep Hydrothermal Vent Euryarchaeota-2 (DHVE-2,
Aciduliprofundum boonei) and the Marine Group-II (MG-II). To better understand
this new order and its relationship to other archaea, we manually curated and
extensively compared the genome sequences of three Methanomassiliicoccales
representatives derived from human GIT microbiota, "Candidatus
Methanomethylophilus alvus", "Candidatus Methanomassiliicoccus intestinalis" and
Methanomassiliicoccus luminyensis. RESULTS: Comparative analyses revealed
atypical features, such as the scattering of the ribosomal RNA genes in the
genome and the absence of eukaryotic-like histone gene otherwise present in most
of Euryarchaeota genomes. Previously identified in Thermoplasmatales genomes,
these features are presently extended to several completely sequenced genomes of
this large evolutionary branch, including MG-II and DHVE2. The three
Methanomassiliicoccales genomes share a unique composition of genes involved in
energy conservation suggesting an original combination of two main energy
conservation processes previously described in other methanogens. They also
display substantial differences with each other, such as their codon usage, the
nature and origin of their CRISPRs systems and the genes possibly involved in
particular environmental adaptations. The genome of M. luminyensis encodes
several features to thrive in soil and sediment conditions suggesting its larger
environmental distribution than GIT. Conversely, "Ca. M. alvus" and "Ca. M.
intestinalis" do not present these features and could be more restricted and
specialized on GIT. Prediction of the amber codon usage, either as a termination
signal of translation or coding for pyrrolysine revealed contrasted patterns
among the three genomes and suggests a different handling of the Pyl-encoding
capacity. CONCLUSIONS: This study represents the first insights into the genomic
organization and metabolic traits of the seventh order of methanogens. It
suggests contrasted evolutionary history among the three analyzed
Methanomassiliicoccales representatives and provides information on conserved
characteristics among the overall methanogens and among Thermoplasmata.
PMID- 25124553
TI - Bim controls IL-15 availability and limits engagement of multiple BH3-only
proteins.
AB - During the effector CD8+ T-cell response, transcriptional differentiation
programs are engaged that promote effector T cells with varying memory potential.
Although these differentiation programs have been used to explain which cells die
as effectors and which cells survive and become memory cells, it is unclear if
the lack of cell death enhances memory. Here, we investigated effector CD8+ T
cell fate in mice whose death program has been largely disabled because of the
loss of Bim. Interestingly, the absence of Bim resulted in a significant
enhancement of effector CD8+ T cells with more memory potential. Bim-driven
control of memory T-cell development required T-cell-specific, but not dendritic
cell-specific, expression of Bim. Both total and T-cell-specific loss of Bim
promoted skewing toward memory precursors, by enhancing the survival of memory
precursors, and limiting the availability of IL-15. Decreased IL-15 availability
in Bim-deficient mice facilitated the elimination of cells with less memory
potential via the additional pro-apoptotic molecules Noxa and Puma. Combined,
these data show that Bim controls memory development by limiting the survival of
pre-memory effector cells. Further, by preventing the consumption of IL-15, Bim
limits the role of Noxa and Puma in causing the death of effector cells with less
memory potential.
PMID- 25124554
TI - Liver X receptor beta activation induces pyroptosis of human and murine colon
cancer cells.
AB - Liver X receptors (LXRs) have been proposed to have some anticancer properties,
through molecular mechanisms that remain elusive. Here we report for the first
time that LXR ligands induce caspase-1-dependent cell death of colon cancer
cells. Caspase-1 activation requires Nod-like-receptor pyrin domain containing 3
(NLRP3) inflammasome and ATP-mediated P2 * 7 receptor activation. Surprisingly,
LXRbeta is mainly located in the cytoplasm and has a non-genomic role by
interacting with pannexin 1 leading to ATP secretion. Finally, LXR ligands have
an antitumoral effect in a mouse colon cancer model, dependent on the presence of
LXRbeta, pannexin 1, NLRP3 and caspase-1 within the tumor cells. Our results
demonstrate that LXRbeta, through pannexin 1 interaction, can specifically induce
caspase-1-dependent colon cancer cell death by pyroptosis.
PMID- 25124557
TI - A smart "sense-act-treat" system: combining a ratiometric pH sensor with a near
infrared therapeutic gold nanocage.
AB - Herein, we design a "sense-act-treat" system via the combination of a ratiometric
pH sensor with a therapeutic gold nanocage. Our design could "sense" the tumor
through two-state switching of fluorescence and further provide chemotherapy and
hyperthermia for "treating" the tumor, showing the potential for future
biomedical applications.
PMID- 25124556
TI - GRP78 clustering at the cell surface of neurons transduces the action of
exogenous alpha-synuclein.
AB - Mutation or multiplication of the alpha-synuclein (Syn)-encoding gene is frequent
cause of early onset Parkinson's disease (PD). Recent evidences point to the
pathogenic role of excess Syn also in sporadic PD. Syn is a cytosolic protein,
which has been shown to be released from neurons. Here we provide evidence that
extracellular Syn induces an increase in surface-exposed glucose-related protein
of 78 kDa (GRP78), which becomes clustered in microdomains of the neuronal plasma
membrane. Upon interacting with Syn, GRP78 activates a signaling cascade leading
to cofilin 1 inactivation and stabilization of microfilaments, thus affecting
morphology and dynamics of actin cytoskeleton in cultured neurons. Downregulation
of GRP78 abolishes the activity of exogenous Syn, indicating that it is the
primary target of Syn. Inactivation of cofilin 1 and stabilization of actin
cytoskeleton are present also in fibroblasts derived from genetic PD patients,
which show a dramatic increase in stress fibers. Similar changes are displayed by
control cells incubated with the medium of PD fibroblasts, only when Syn is
present. The accumulation of Syn in the extracellular milieu, its interaction
with the plasma membrane and Syn-driven clustering of GRP78 appear, therefore,
responsible for the dysregulation of actin turnover, leading to early deficits in
synaptic function that precede neurodegeneration.
PMID- 25124558
TI - Descriptive epidemiology of colorectal cancer in University Malaya Medical
Centre, 2001 to 2010.
AB - BACKGROUND: Colorectal cancer is the second most frequent cancer in Malaysia.
Nevertheless, there is little information on treatment and outcomes nationally.
We aimed to determine the demographic, clinical and treatment characteristics of
colorectal cancer patients treated at the University Malaya Medical Centre (UMMC)
as part of a larger project on survival and quality of life outcomes. MATERIALS
AND METHODS: Medical records of 1,212 patients undergoing treatment in UMMC
between January 2001 and December 2010 were reviewed. A retrospective-prospective
cohort study design was used. Research tools included the National Cancer Patient
Registration form. Statistical analysis included means, standard deviations (SD),
proportions, chi square, t-test/ ANOVA. P-value significance was set at 0.05.
RESULTS: The male: female ratio was 1.2:1. The mean age was 62.1 (SD12.4) years.
Patients were predominantly Chinese (67%), then Malays (18%), Indians (13%) and
others (2%). Malays were younger than Chinese and Indians (mean age 57 versus 62
versus 62 years, p<0.001). More females (56%) had colon cancers compared to males
(44%) (p=0.022). Malays (57%) had more rectal cancer compared to Chinese (45%)
and Indians (49%) (p=0.004). Dukes' stage data weres available in 67%, with
Dukes' C and D accounting for 64%. Stage was not affected by age, gender,
ethnicity or tumor site. Treatment modalities included surgery alone (40%),
surgery and chemo/radiotherapy 32%, chemo and radiotherapy (8%) and others (20%).
CONCLUSIONS: Significant ethnic differences in age and site distribution, if
verified in population-based settings, would support implementation of preventive
measures targeting those with the greatest need, at the right age.
PMID- 25124559
TI - Review of the molecular pathogenesis of osteosarcoma.
AB - Treating the osteosarcoma (OSA) remains a challenge. Current strategies focus on
the primary tumor and have limited efficacy for metastatic OSA. A better
understanding of the OSA pathogenesis may provide a rational basis for innovative
treatment strategies especially for metastases. The aim of this review is to give
an overview of the molecular mechanisms of OSA tumorigenesis, OSA cell
proliferation, apoptosis, migration, and chemotherapy resistance, and how
improved understanding might contribute to designing a better treatment target
for OSA.
PMID- 25124560
TI - TRAIL mediated signaling in pancreatic cancer.
AB - Research over the years has progressively shown substantial broadening of the
tumor necrosis factor alpha- related apoptosis-inducing ligand (TRAIL)-mediated
signaling landscape. Increasingly it is being realized that pancreatic cancer is
a multifaceted and genomically complex disease. Suppression of tumor suppressors,
overexpression of oncogenes, epigenetic silencing, and loss of apoptosis are some
of the extensively studied underlying mechanisms. Rapidly accumulating in vitro
and in vivo evidence has started to shed light on the resistance mechanisms in
pancreatic cancer cells. More interestingly a recent research has opened new
horizons of miRNA regulation by DR5 in pancreatic cancer cells. It has been shown
that DR5 interacts with the core microprocessor components Drosha and DGCR8, thus
impairing processing of primary let-7. Xenografting DR5 silenced pancreatic
cancer cells in SCID-mice indicated that there was notable suppression of tumor
growth. There is a paradigm shift in our current understanding of TRAIL mediated
signaling in pancreatic cancer cells that is now adding new layers of concepts
into the existing scientific evidence. In this review we have attempted to
provide an overview of recent advances in TRAIL mediated signaling in pancreatic
cancer as evidenced byfindings of in vitro and in vivo analyses. Furthermore, we
discuss nanotechnological advances with emphasis on PEG-TRAIL and four-arm PEG
cross-linked hyaluronic acid (HA) hydrogels to improve availability of TRAIL at
target sites.
PMID- 25124555
TI - KMTase Set7/9 is a critical regulator of E2F1 activity upon genotoxic stress.
AB - During the recent years lysine methyltransferase Set7/9 ((Su(var)-3-9, Enhancer
of-Zeste, Trithorax) domain containing protein 7/9) has emerged as an important
regulator of different transcription factors. In this study, we report a novel
function for Set7/9 as a critical co-activator of E2 promoter-binding factor 1
(E2F1)-dependent transcription in response to DNA damage. By means of various
biochemical, cell biology, and bioinformatics approaches, we uncovered that cell
cycle progression through the G1/S checkpoint of tumour cells upon DNA damage is
defined by the threshold of expression of both E2F1 and Set7/9. The latter
affects the activity of E2F1 by indirectly modulating histone modifications in
the promoters of E2F1-dependent genes. Moreover, Set7/9 differentially affects
E2F1 transcription targets: it promotes cell proliferation via expression of the
CCNE1 gene and represses apoptosis by inhibiting the TP73 gene. Our biochemical
screening of the panel of lung tumour cell lines suggests that these two factors
are critically important for transcriptional upregulation of the CCNE1 gene
product and hence successful progression through cell cycle. These findings
identify Set7/9 as a potential biomarker in tumour cells with overexpressed E2F1
activity.
PMID- 25124561
TI - Emerging and established global life-style risk factors for cancer of the upper
aero-digestive tract.
AB - INTRODUCTION: Upper aero-digestive tract cancer is a multidimensional problem,
international trends showing complex rises and falls in incidence and mortality
across the globe, with variation across different cultural and socio-economic
groups. This paper seeks some explanations and identifies some research and
policy needs. METHODOLOGICAL APPROACH: The literature illustrates the
multifactorial nature of carcinogenesis. At the cellular level, it is viewed as a
multistep process involving multiple mutations and selection for cells with
progressively increasing capacity for proliferation, survival, invasion, and
metastasis. Established and emerging risk factors, in addition to changes in
incidence and prevalence of cancers of the upper aero-digestive tract, were
identified. RISK FACTORS: Exposure to tobacco and alcohol, as well as diets
inadequate in fresh fruits and vegetables, remain the major risk factors, with
persistent infection by particular so-called "high risk" genotypes of human
papillomavirus increasingly recognised as also playing an important role in a
subset of cases, particularly for the oropharynx. Chronic trauma to oral mucosa
from poor restorations and prostheses, in addition to poor oral hygiene with a
consequent heavy microbial load in the mouth, are also emerging as significant
risk factors. CONCLUSIONS: Understanding and quantifying the impact of individual
risk factors for these cancers is vital for health decision-making, planning and
prevention. National policies and programmes should be designed and implemented
to control exposure to environmental risks, by legislation if necessary, and to
raise awareness so that people are provided with the information and support they
need to adopt healthy lifestyles.
PMID- 25124562
TI - Functional roles of long non-coding RNA in human breast cancer.
AB - The discovery of long noncoding RNA (LncRNA) changes our view of transcriptional
and posttranscriptional regulation of gene expression. With application of new
research techniques such as high-throughput sequencing, the biological functions
of LncRNAs are gradually becoming to be understood. Multiple studies have shown
that LncRNAs serve as carcinogenic factors or tumor suppressors in breast cancer
with abnormal expression, prompts the question of whether they have potential
value in predicting the stages and survival rate of breast cancer patients, and
also as therapeutic targets. Focusing on the latest research data, this review
mainly summarizes the tumorigenic mechanisms of certain LncRNAs in breast cancer,
in order to provide a theoretical basis for finding safer, more effective
treatment of breast cancer at the LncRNA molecular level.
PMID- 25124563
TI - Critical review on the carcinogenic potential of pesticides used in Korea.
AB - Pesticides used in Korea are grouped by four classes of hazard (extremely,
highly, moderately and slightly hazardous) based on acute oral and dermal
toxicity in the rat. However, there is little information of carcinogenic
effects. The aim of this study was to evaluate potential carcinogenicity for
active ingredients of pesticides used in Korea. A total of 1,283 pesticide items
were registered under the Pesticide Control Act of which 987 were commercially
available. Of these 987 items, 360 active ingredients not duplicated were
evaluated for carcinogenicity using the carcinogen list established by the US
Environmental Protection Agency (EPA). Some 25 out of 360 ingredients were
classified as likely to be carcinogenic (probable) to humans and 52 had
suggestive evidence of carcinogenic potential (suspected) based on the US EPA
classification. Some 31% of 987 items contained probable or suspected human
carcinogenic ingredients. Carcinogenic pesticides accounted for 24% (5,856/24,795
tons) of the total volume of consumption in Korea. Interestingly, pesticides with
lower acute toxicity were found to have higher carcinogenic potential. Based on
these findings, the study suggests that it is important to provide information on
long-term toxicity to farmers, in addition to acute toxicity data.
PMID- 25124564
TI - Comparison of recurrence rates with contour-loop excision of the transformation
zone (C-LETZ) and large loop excision of the transformation zone (LLETZ) for CIN.
AB - AIM: To compare recurrence rates of large loop excision of the transformation
zone (LLETZ) with those of contour-loop excision of the transformation zone (C
LETZ) in the management of cervical intraepithelial neoplasia (CIN). MATERIALS
AND METHODS: The medical records of 177 patients treated consecutively by LLETZ
and C-LETZ for CIN at Rajavithi Hospital between 2006 and 2009 were
retrospectively reviewed. RESULTS: Of the 87 women in the C-LETZ group, 2 cases
(2.30%) had recurrence compared with 13 cases (14.4%) of the 90 women in the
LLETZ group, the higher recurrence rate in the latter being statistically
significant (p<0.05). Median times of follow up in the C-LETZ and LLETZ groups
were 12 months and 14 months respectively (p>0.05). The C-LETZ group showed less
intraoperative bleeding compared to the LLETZ group, but the rate of achievement
of single specimens and positive margins were similar in the two groups.
CONCLUSIONS: The present study demonstrated the superiority of C-LETZ over LLETZ
in terms of efficacy; C-LLETZ is associated with a lower recurrence rate and also
carries a smaller risk of intraoperative bleeding than LLETZ. The rotating
technique still has a potential role in treating precancerous lesions of the
cervix.
PMID- 25124565
TI - Impact of cellular immune function on prognosis of lung cancer patients after
cytokine-induced killer cell therapy.
AB - AIMS: To investigate changes in cellular immune function of patients with lung
cancer before and after cytokine- induced killer (CIK) cell therapy and to
identify variation effects on overall survival (OS) and progression-free survival
(PFS). MATERIALS AND METHODS: A total of 943 lung cancer patients with immune
dysfunction were recruited from January 2002 to January 2010, 532 being allocated
to conventional therapy and 411 to CIK therapy after a standard treatment
according to the NCCN Clinical Practice Guidelines. All the patients were
investigated for cellular immune function before and after therapy every three
months. and clinical prognostic outcomes were analyzed. RESULTS: After six
courses of treatment, immune function was much improved in patients receiving CIK
cells therapy as compared to controls. The percentages of recurrence and/or
metastases for patients undergoing CIK cell therapy was 56.2% and 49.1%
respectively but 78.6% and 70.3% among controls (p<0.001). The median OS times
for CIK cell therapy and control groups were 48 and 36 months respectively. The
OS rates at 12, 36, 60, 84 months in CIK treated patients were 97.8%, 66.9%,
27.7%, and 4.1% while they were 92.3%, 44.5%, 9.2%, and 1.5% in controls. OS and
PFS were significantly different by log rank test between the two groups and
across the three immune improvement classes. CONCLUSIONS: The immune function of
lung cancer patients was improved by CIK cell therapy, associated with an
increase in the OS rate and extension of the time to recurrence and/or
metastasis.
PMID- 25124566
TI - Prognostic role of circulating tumor cells in patients with pancreatic cancer: a
meta-analysis.
AB - BACKGROUND: Isolation and characterization of circulating tumor cells (CTCs) in
patients suffering from a variety of different cancers have become hot biomarker
topics. In this study, we evaluated the prognostic value of CTCs in pancreatic
cancer. MATERIALS AND METHODS: Initial literature was identified using Medline
and EMBASE. The primary data were hazard ratios (HRs) with 95% confidence
intervals (CIs) of survival outcomes, including overall survival (OS) and
progression free survival/recurrence free survival (PFS/RFS). RESULTS: A total of
9 eligible studies were included in this meta-analysis, published between 2002
and 2013. The estimated pooled HR and 95%CI for OS for all studies was 1.64
(95%CI 1.39-1.94, p<0.00001) and the pooled HR and 95%CI for RFS/DFS was 2.36
(95%CI 1.41-3.96, p<0.00001). The HRs and 95%CIs for OS and RFS/ DFS in patients
before treatment were 1.93 (95%CI 1.26-2.96, p=0.003) and 1.82 (95%CI 1.22-2.72,
p=0.003), respectively. In patients receiving treatment, the HRs and 95%CI for OS
and RFS/DFS were 1.37 (95%CI 1.00- 1.86, p=0.05) and 1.89 (95%CI 1.01-3.51,
p=0.05), respectively. Moreover, the pooled HR and 95%CI for OS in the post
treatment group was 2.20 (95%CI 0.80-6.02, p=0.13) and the pooled HR for RFS/DFS
was 8.36 (95%CI 3.22-21.67, p<0.0001). CONCLUSIONS: The meta-analysis provided
strong evidence supporting the proposition that CTCs detected in peripheral blood
have a fine predictive role in pancreatic patients especially on the time point
of post-treatment.
PMID- 25124567
TI - Upregulation of STK15 in esophageal squamous cell carcinomas in a Mongolian
population.
AB - BACKGROUND: The STK15 gene located on chromosome 20q13.2 encodes a centrosome
associated kinase critical for regulated chromosome segregation and cytokinesis.
Recent studies have demonstrated STK15 to be significantly associated with many
tumors, with aberrant expression obseved in many human malignancies. The purpose
of this study was to investigate expression of STK15 in esophageal squamous cell
carcinomas (ESCCs) in a Mongolian population. METHODS: Two non-synonymous single
nucleotide polymorphisms in the coding region of STK15, rs2273535 (Phe31Ile) and
rs1047972 (Val57Ile) were assessed in 380 ESCC patients and 380 healthy controls.
We also detected STK15 mRNA expression in 39 esophageal squamous cell carcinomas
and corresponding adjacent tissues by real time PCR. RESULTS: rs2273535 showed a
significant association with ESCC in our Mongolian population (rs227353, P
allele=0.0447, OR (95%CI)=1.259 (1.005~1.578)). Real time PCR analysis of ESCC
tissues showed that expression of STK15 mRNA in cancer tissues was higher than in
normal tissues (p=0.013). CONCLUSIONS: Our study showed that functional SNPs in
the STK15 gene are associated with ESCC in a Mongolian population and up
regulation of STK15 mRNAoccurs in ESCC tumors compared adjacent normal tissues.
STK15 may thus have an important role in the prognosis of ESCC and be a potential
therapeutic target.
PMID- 25124568
TI - Survival analysis of biliary tract cancer cases in Turkey.
AB - BACKGROUND: Because of the relative rarity of biliary tract cancers (BTCs),
defining long term survival results is difficult. In the present study, we aimed
to evaluate the survival of a series of cases in Turkey. MATERIALS AND METHODS: A
totally of 47 patients with billiary tract cancer from Mersin Goverment Hospital,
Acibadem Kayseri Hospital and Kayseri Training and Research Hospital were
analyzed retrospectively using hospital records between 2006-2012. RESULTS: The
median overall survival was 19.3+/-3.9 months for all patients. The median
disease free and overall survivals were 24.3+/-5.3 and 44.1+/-12.9 months in
patients in which radical surgery was performed , but in those with with
inoperable disease they were only 5.3+/-1.5 and 10.7+/-3.2 months, respectively.
CONCLUSIONS: BTCs have a poor prognosis. Surgery with a microscopic negative
margin is still the only curative treatment.
PMID- 25124569
TI - Comparison of survival rates between Chinese and Thai patients with breast
cancer.
AB - BACKGROUND: The burden and severity of a cancer can be reflected by patterns of
survival. Breast cancer prognosis between two countries with a different
socioeconomic status and cultural beliefs may exhibit wide variation. This study
aimed to describe survival in patients with breast cancer in China and Thailand
in relation to demographic and clinical prognostic information. MATERIALS AND
METHODS: We compared the survival of 1,504 Chinese women in Yunnan province and
929 Thai women in Songkhla with breast cancer from 2006 to 2010. Descriptive
prognostic comparisons between the Chinese and Thai women were performed by
relative survival analysis. A Cox regression model was used to calculate the
hazard ratios of death, taking into account the age, disease stage, period of
diagnosis and country. RESULTS: The overall 5-year survival proportion for
patients diagnosed with breast cancer for Yunnan province (0.72) appeared
slightly better than Songkhla (0.70) without statistical significance. Thai women
diagnosed with distant and regional breast cancer had poorer survival than
Chinese women. Disease stage was the most important determinant of survival from
the results of Cox regression model. CONCLUSIONS: Breast cancer patients in
Kunming had slightly greater five-year survival rate than patients in Songkhla.
Both Chinese and Thai women need improvement in prognosis, which could
conceivably be attained through increased public education and awareness
regarding early detection and compliance to treatment protocols.
PMID- 25124570
TI - Parathyroid hormone gene rs6256 and calcium sensing receptor gene rs1801725
variants are not associated with susceptibility to colorectal cancer in Iran.
AB - BACKGROUND: Substantial evidence from epidemiological studies has suggested that
increased levels of calcium may play a protective role against colorectal cancer
(CRC). Given the vital role of calcium sensing receptor (CaSR) and parathyroid
hormone (PTH) in the maintenance of calcium homeostasis, we explored whether the
rs1801725 (A986S) variant located in exon 7 of the CaSR gene and the rs6256
variant located in exon 3 of PTH gene might be associated with CRC risk.
MATERIALS AND METHODS: In this study 860 subjects including 350 cases with CRC
and 510 controls were enrolled and genotyped using PCR-RFLP methods. RESULTS: We
observed no significant difference in genotype or allele frequencies between the
cases with CRC and controls for both CaSR and PTH genes either before or after
adjustment for confounding factors including age, BMI, sex, smoking status, and
family history of CRC. Furthermore, no evidence for effect modification of any
association of rs1801725 and rs6256 variants and CRC by BMI, sex, or tumor site
was observed. In addition, there was no significant difference in genotype and
allele frequencies between the normal weight (BMI<25 kg/m2) cases and overweight/
obese (BMI>=25 kg/m2) cases for the two SNPs. CONCLUSIONS: These data indicated
that the CaSR gene A986S variant is not a genetic contributor to CRC risk in the
Iranian population. Furthermore, our results suggest for the first time that PTH
gene variant does not affect CRC risk. Nonetheless, further studies with larger
sample size are needed to validate these findings.
PMID- 25124572
TI - Weight loss correlates with macrophage inhibitory cytokine-1 expression and might
influence outcome in patients with advanced esophageal squamous cell carcinoma.
AB - BACKGROUND: Weight loss during chemotherapy has not been exclusively
investigated. Macrophage inhibitory cytokine-1 (MIC-1) might play a role in its
etiology. Here, we investigated the prognostic value of weight loss before
chemotherapy and its relationship with MIC-1 concentration and its occurrence
during chemotherapy in patients with advanced esophageal squamous cell carcinoma
(ESCC). MATERIALS AND METHODS: We analyzed 157 inoperable locally advanced or
metastatic ESCC patients receiving first-line chemotherapy. Serum MIC-1
concentrations were assessed before chemotherapy. Patients were assigned into two
groups according to their weight loss before or during chemotherapy: >5% weight
loss group and<=5% weight loss group. RESULTS: Patients with weight loss>5%
before chemotherapy had shorter progression-free survival period (5.8 months vs.
8.7 months; p=0.027) and overall survival (10.8 months vs. 20.0 months; p=0.010).
Patients with weight loss>5% during chemotherapy tended to have shorter
progression-free survival (6.0 months vs. 8.1 months; p=0.062) and overall
survival (8.6 months vs. 18.0 months; p=0.022), and if weight loss was reversed
during chemotherapy, survival rates improved. Furthermore, serum MIC-1
concentration was closely related to weight loss before chemotherapy (p=0.001)
CONCLUSIONS: Weight loss both before and during chemotherapy predicted poor
outcome in advanced ESCC patients, and MIC-1 might be involved in the development
of weight loss in such patients.
PMID- 25124571
TI - Computed tomography manifestations of histologic subtypes of retroperitoneal
liposarcoma.
AB - OBJECTIVE: Liposarcoma (LPS) is the most common soft tissue sarcoma and accounts
for approximately 20% of all mesenchymal malignancies, often occurring in deep
soft tissue of retroperitoneal space. Accurate preoperative diagnosis is
therefore necessary. We explored whether computed tomography (CT) could be used
to differentiate between the various types of retroperitoneal liposarcoma (RPLS).
METHOD: Forty-seven cases of RPLS, diagnosed surgically and histologically, were
analyzed retrospectively. CT features were correlated with postoperative
pathological appearance. RESULTS: The study radiologist identified 29, 11, 2, 2
and 3 RPLS as atypical lipomatous tumor/well-differentiated liposarcoma
(ALT/WDL), dedifferentiated liposarcoma (DDL), myxoid/round cell liposarcoma
(ML/RCL), pleomorphic liposarcoma (PL) and mixed-type liposarcoma. Analysis of CT
scans revealed the following typical findings of the different subtypes of RPLS:
ALT/WDL was mainly visible as a well-delineated fatty hypodense tumor with
uniform density and integrity margin; DDL was marked by the combination of focal
nodular density and hypervascularity. ML/RCL, PL and mixed liposarcoma showed
malignant biological behaviour and CT findings need further studies. CONCLUSIONS:
CT scanning can reveal important details including internal components, margins
and surrounding tissues. Based on CT findings, tumor type can be roughly
evaluated and biopsy location and therapeutic scheme guided.
PMID- 25124573
TI - Utility of frozen section pathology with endometrial pre-malignant lesions.
AB - AIM: To determine utility of the frozen section (FS) in the operative management
of endometrial pre-malignant lesions. MATERIALS AND METHODS: We retrospectively
analyzed patients who underwent abdominal hysterectomy with preoperative
diagnosis of complex atypical endometrial hyperplasia (CAEH) and simple
endometrial hyperplasia (SEH) between May 2007 and December 2013. Frozen and
paraffin section (PS) results were compared. Sensitivity, specificity, the
positive predictive value (PPV), the negative predictive value (NPV) and the
accuracy in predicting EC on FS were evaluated with 95% confidence intervals
(CIs) for each parameter. The correlation between FS and PS was calculated as an
kappa coefficient. RESULTS: Among 143 preoperatively diagnosed CAEH cases, 60
(42%) were malignant and 83 (58%) were benign in PS; and among 60 malignant cases
diagnosed in PS, 43 (71%) were "malignant" in FS. Sensitivity, specificity, PPV
and NPV for FS were 76%, 100%, 100% and 87.5%, respectively. CONCLUSIONS: We
found that FS is reliable and applicable in the management of endometrial
hyperplasias. It is important that the pathologist should be experienced because
FS for endometrial pre-malignant lesions has significant inter-observer
variability. The other conclusion is that patients with the diagnosis of EH,
especially those who are postmenopausal, should undergo surgery where FS
investigation is available.
PMID- 25124574
TI - SLC35B2 expression is associated with a poor prognosis of invasive ductal breast
carcinoma.
AB - BACKGROUND: Breast cancer is the most common malignancy in women worldwide,
including Thailand, and is a major cause of mortality and morbidity, despite
advances in diagnosis and treatment. Novel gene expression in breast cancer is a
focus in searches for prognostic biomarkers and new therapeutic targets.
MATERIALS AND METHODS: The mRNA expression of novel B4GALT4, SLC35B2, and WDHD1
genes in breast cancer were examined in invasive ductal breast carcinoma (IDC)
patients using quantitative real-time reverse transcription polymerase chain
reaction (QRT-PCR). RESULTS: Among these genes, increased expression of SLC35B2
mRNA was significantly associated with TNM stage III+IV of IDC (p<0.001). Hence,
up-regulation of SLC35B2 may serve as a prognostic biomarker for poor prognosis,
and is also a potential therapeutic target in breast cancer.
PMID- 25124576
TI - Distinct pro-apoptotic properties of Zhejiang saffron against human lung cancer
via a caspase-8-9-3 cascade.
AB - Lung cancer is the leading cause of cancer-related death worldwide. Here we
investigated the antitumor effect and mechanism of Zhejiang (Huzhou and Jiande)
saffron against lung cancer cell lines, A549 and H446. Using high performance
liquid chromatography (HPLC), the contents of crocin I and II were determined. In
vitro, MTT assay and annexin-V FITC/PI staining showed cell proliferation
activity and apoptosis to be changed in a dose- and time-dependent manner. The
inhibition effect of Jiande saffron was the strongest. In vivo, when mice were
orally administered saffron extracts at dose of 100mg/kg/d for 28 days, xenograft
tumor size was reduced, and ELISA and Western blotting analysis of caspase-3, -8
and -9 exhibited stronger expression and activity than in the control. In
summary, saffron from Zhejiang has significant antitumor effects in vitro and in
vivo through caspase-8-caspase-9-caspase-3 mediated cell apoptosis. It thus
appears to have more potential as a therapeutic agent.
PMID- 25124575
TI - Association of Rs11615 (C>T) in the excision repair cross-complementing group 1
gene with ovarian but not gynecological cancer susceptibility: a meta-analysis.
AB - BACKGROUND: Evidence suggests that the rs11615 (C>T) polymorphism in the ERCC1
gene may be a risk factor for gynecological tumors. However, results have not
been consistent. Therefore we performed this meta- analysis. METHODS: Eligible
studies were identified by search of PubMed, MEDLINE and Chinese National
Knowledge Infrastructure (CNKI). Odds ratios (ORs) and 95% confidence intervals
(CIs) were applied to assess associations between rs11615 (C>T) and gynecological
tumor risk. Heterogeneity among studies was tested and sensitivity analysis was
applied. RESULTS: A total of 6 studies were identified, with 1,766 cases and
2,073 controls. No significant association was found overall between the rs11615
(C>T) polymorphism and gynecological tumor susceptibility in any genetic model.
In further analysis stratified by cancer type, significantly elevated ovarian
cancer risk was observed in the homozygote and recessive model comparison (TT vs
CC: OR=1.69, 95% CI=1.03-2.77, heterogeneity=0.876; TT vs CT/CC: OR=1.72, 95%
CI=1.07-2.77, heterogeneity=0.995). CONCLUSION: The results of the present meta
analysis suggest that there is no significant association between the rs11615
(C>T) polymorphism and gynecological tumor risk, but it had a increased risk in
ovarian cancer.
PMID- 25124577
TI - Effectiveness of the Microlux/DLTM chemiluminescence device in screening of
potentially malignant and malignant oral lesions.
AB - BACKGROUND: To evaluate the effectiveness of Microlux/DL with and without
toluidine blue in screening of potentially malignant and malignant oral lesions.
MATERIALS AND METHODS: In this diagnostic clinical trial clinical examination was
carried out by two teams: 1) two oral medicine consultants, and 2) two general
dentists. Participants were randomly and blindly allocated for each examining
team. A total of 599 tobacco users were assessed through conventional oral
examination (COE); the examination was then repeated using Microlux/DL device and
toluidine blue. Biopsy of suspicious lesions was performed. Also clinicians
opinions regarding the two tools were obtained. RESULTS: The sensitivity and,
specificity and positive predictive value (PVP) of Microlux/DL for visualization
of suspicious premalignant lesions considering COE as a gold standard (i.e
screening device) were 94.3%, 99.6% and 96.2% respectively, while they were 100%,
32.4% and 17.9% when considering biopsy as a gold standard. Moreover, Microlux/DL
enhanced detection of the lesion and uncovered new lesions compared to COE,
whereas it did not alter the provisional clinical diagnosis, or alter the biopsy
site. On the other hand, adding toluidine blue dye did not improve the
effectiveness of the Microlux/DL system. CONCLUSIONS: The Microlux/DL seems to be
a promising adjunctive screening device.
PMID- 25124578
TI - Impact of prognostic factors on survival rates in patients with ovarian
carcinoma.
AB - PURPOSE: The aim of the present study was to invesitigate the impact of
significant clinico-pathological prognostic factors on survival rates and to
identify factors predictive of poor outcome in patients with ovarian carcinoma.
MATERIALS AND METHODS: A retrospective chart review of 74 women with
pathologically proven ovarian carcinoma who were treated between January 2006 and
April 2011 was performed. Patients were investigated with respect to survival to
find the possible effects of age, gravida, parity, menstruel condition, pre
operative Ca-125, treatment period, cytologic washings, presence of ascites,
tumor histology, stage and grade, maximal tumor diameter, adjuvan chemotherapy
and cytoreductive success. Also 55 ovarian carcinoma patients were investigated
with respect to prognostic factors for early 2-year survival. RESULTS: The two
year survival rate was 69% and the 5-year survival rate was 25.5% for the whole
study population. Significant factors for 2-year survival were preoperative CA
125 level, malignant cytology and FIGO clinical stage. Significant factors for 5
year survival were age, preoperative CA-125 level, residual tumor, lymph node
metastases, histologic type of tumor, malignant cytology and FIGO clinical stage.
Logistic regression revealed that independent prognostic factors of 5-year
survival were patient age, lymph node metastasis and malignant cytology.
CONCLUSIONS: We consider quality registries with prospectively collected data to
be one important tool in monitoring treatment effects in population-based cancer
research.
PMID- 25124579
TI - Perception and practices on screening and vaccination for carcinoma cervix among
female healthcare professional in tertiary care hospitals in Bangalore, India.
AB - BACKGROUND: Cervical cancer is potentially the most preventable and treatable
cancer. Despite the known efficacy of cervical screening, a significant number of
women do not avail themselves of the procedure due to lack of awareness.
OBJECTIVES: This study was conducted to elicit information on the knowledge,
attitude and practice (KAP) regarding screening (Pap test) and vaccination for
carcinoma cervix among female doctors and nurses in a tertiary care hospital in
Bangalore and to assess barriers to acceptance of the Pap test. MATERIALS AND
METHODS: A cross-sectional, descriptive study was conducted with semi-structured,
self-administered questionnaire among female health professionals. The study
subjects were interviewed for KAP regarding risk factors for cancer cervix, Pap
test and HPV vaccination for protection against carcinoma cervix. RESULTS: Higher
proportion of doctors 45 (78.9%) had very good knowledge as compared to only 13
(13.3%) of the nurses, about risk factors for cancer cervix and Pap test
(p=0.001). As many as 138(89.6%) of the study subjects had favorable attitude
towards Pap test and vaccination, but 114 (73.6%) of the study subjects never had
a Pap test and the most common reason 35 (31%) for not practicing was absence of
disease symptoms. CONCLUSIONS: In spite of good knowledge and attitudes towards
cancer cervix and Pap test being good, practice remained low among the study
subjects and most common reasons for not undergoing Pap test was absence of
disease symptoms. The independent predictors of ever having a Pap test done was
found to be the occupation and duration of married life above 9 yrs. Hence there
is a strong need to improve uptake of Pap test by health professionals by
demystifying the barriers.
PMID- 25124580
TI - Elevated serum ferritin levels in patients with hematologic malignancies.
AB - PURPOSE: To retrospectively analyze variability and clinical significance of
serum ferritin levels in Chinese patients with hematologic malignancies.
MATERIALS AND METHODS: Serum ferritin were measured by radioimmunoassay, using a
kit produced by the Beijing Institute of Atomic Energy. Patients with hematologic
malignancies, and treated in the Department of Hematology in Nanjing First
Hospital and fulfilled study criteria were recruited. RESULTS: Of 473 patients
with hematologic malignancies, 262 patients were diagnosed with acute leukemia,
131 with lymphoma and 80 with multiple myeloma. Serum ferritin levels of newly
diagnosed and recurrent patients were significantly higher than those entering
complete remission stage or in the control group (p<0.001). CONCLUSIONS: Serum
ferritin lever in patients with hematologic malignancies at early stage and
recurrent stage are significantly increased, so that detection and surveillance
of changes of serum ferritin could be helpful in assessing conditions and
prognosis of this patient cohort.
PMID- 25124581
TI - Prognostic significance of beta-catenin expression in patients with esophageal
carcinoma: a meta-analysis.
AB - Many studies have reported beta-catenin involvement in the development of
esophageal carcinoma (EC), but its prognostic significance for EC patients
remains controversial. Therefore, we conducted this meta-analysis to explore the
issue in detail. After searching PubMed, EMBASE, Web of Science, and Chinese
Biomedical Literature Database, we included a total of ten relevant studies. We
pooled the overall survival (OS) data using RevMan 5.2 software. The results
showed that aberrant expression of beta-catenin was associated with a significant
increase of mortality risk (hazard ratio 1.71, 95%CI 1.46-2.01; p<0.00001).
Subgroup analyses further suggested that aberrant expression of beta-catenin
resulted in poor OS of EC patients regardless of histological type of EC, study
location or criteria for aberrant expression of beta-catenin, and the sensitivity
analyses revealed that the result was robust. The meta-analysis revealed that
aberrant expression of beta-catenin could be a predicative factor of poor
prognosis for EC patients.
PMID- 25124582
TI - Clinicopathological features of indonesian breast cancers with different
molecular subtypes.
AB - BACKGROUND: Breast cancer is a heterogeneous disease with molecular subtypes that
have biological distinctness and different behavior. They are classified into
luminal A, luminal B, Her-2 and triple negative/basal-like molecular subtypes.
Most of breast cancers reported in Indonesia are already large size, with high
grade or late stage but the clinicopathological features of different molecular
subtypes are still unclear. They need to be better clarified to determine proper
treatment and prognosis. AIM: To elaborate the clinicopathological features of
molecular subtypes of breast cancers in Indonesian women. MATERIALS AND METHODS:
A retrospective cross-sectional study of 84 paraffin-embedded tissues of breast
cancer samples from Dr. Sardjito General Hospital in Central Java, Indonesia was
performed. Expression of ER, PR, Her-2 and Ki-67 was analyzed to classify
molecular subtypes of breast cancer by immunohistochemistry. The relation of
clinicopathological features of breast cancers with molecular subtypes of luminal
A, luminal B, Her-2 and triple negative/basal-like were analyzed using Pearson's
Chi-Square test. A p-value of <0.05 was considered statistically significant.
RESULTS: Case frequency of luminal A, Luminal B, Her-2+ and triple negative/basal
like subtypes were 38.1%, 16.7%, 20.2% and 25%, respectively. Significant
difference was found in breast cancer molecular subtypes in regard to age,
histological grade, lymph node status and staging. However it showed
insignificant result in regard to tumor size. Luminal A subtype of breast cancer
was commonly found in >50 years old women (p:0.028), low grade cancer (p:0.09),
negative lymph node metastasis (p:0.034) and stage III (p:0.017). Eventhough the
difference was insignificant, luminal A subtype breast cancer was mostly found in
small size breast cancer (p:0.129). Her-2+ subtype breast cancer was more
commonly diagnosed with large size, positive lymph node metastasis and poor
grade. Triple negative/basal-like cancer was mostly diagnosed among <50 years old
women. CONCLUSIONS: This study suggests that immunohistochemistry-based subtyping
is essential to classify breast carcinoma into subtypes that vary in
clinicopathological features, implying different therapeutic options and
prognosis for each subtype.
PMID- 25124583
TI - Comparisons between the KKU-model and conventional rectal tubes as markers for
checking rectal doses during intracavitary brachytherapy of cervical cancer.
AB - BACKGROUND: To compare the KKU-model rectal tube (KKU-tube) and the conventional
rectal tube (CRT) for checking rectal doses during high-dose-rate intracavitary
brachytherapy (HDR-ICBT) of cervical cancer. MATERIALS AND METHODS: Between
February 2010 and January 2011, thirty -two patients with cervical cancer were
enrolled and treated with external beam radiotherapy (EBRT) and intracavitary
brachytherapy (ICBT). The KKU-tube and CRT were applied intrarectally in the same
patients at alternate sessions as references for calculation of rectal doses
during ICBT. The gold standard references of rectum anatomical markers which are
most proximal to radiation sources were anterior rectal walls (ARW) adjacent to
the uterine cervix demonstrated by barium sulfate suspension enema. The
calculated rectal doses derived from actual anterior rectal walls, CRT and the
anterior surfaces of the KKU-tubes were compared by using the paired t-test. The
pain caused by insertion of each type of rectal tube was assessed by the visual
analogue scale (VAS). RESULTS: The mean dose of CRT was lower than the mean dose
of ARW (Dmean0-Dmean1) by 80.55+/-47.33 cGy (p-value<0.05). The mean dose of the
KKU-tube was lower than the mean dose of ARW (Dmean0-Dmean2) by 30.82+/-24.20 cGy
(p-value<0.05). The mean dose difference [(Dmean0-Dmean1)-(Dmean0-Dmean2)] was
49.72+/-51.60 cGy, which was statistically significant between 42.32 cGy -57.13
cGy with the t-value of 13.24 (p-value<0.05). The maximum rectal dose by using
CRT was higher than the KKU-tube as much as 75.26 cGy and statistically
significant with the t-score of 7.55 (p-value<0.05). The mean doses at the
anterior rectal wall while using the CRTs and the KKU-tubes were not
significantly different (p-value=0.09). The mean pain score during insertion of
the CRT was significantly higher than the KKU-tube by a t-score of 6.15 (p
value<0.05) CONCLUSIONS: The KKU-model rectal tube was found to be an easily
producible, applicable and reliable instrument as a reference for evaluating the
rectal dose during ICBT of cervical cancer without negative effects on the
patients.
PMID- 25124584
TI - Prostate-specific antigen levels in relation to background factors: are there
links to endocrine disrupting chemicals and AhR expression?
AB - BACKGROUND: Prostate-specific antigen (PSA) is a potential biomarker for early
detection of prostate cancer (PCa) but its level is known to be affected by many
background factors and roles of ubiquitous toxicants have not been determined.
Endocrine disrupting chemicals (EDCs) are ubiquitous reproductive toxicants used
in consumer products, which promote tumor formation in some reproductive model
systems by binding to AhR, but human data on its expression in prostate cancer as
well as its association with PSA levels are not clear. This study aimed to
evaluate the expression levels of AhR and its association with serological levels
of PSA and to detect possible effects of background factors and EDC exposure
history on PSA levels in PCa cases. MATERIALS AND METHODS: A cross-sectional
study was conducted on the tissue levels of AhR and serum levels of PSA in 53 PCa
cases from 2008-2011 and associations between each and background and lifestyle
related factors were determined. RESULTS: Although the AhR was overexpressed in
PCa and correlated with the age of patients, it did not correlate with PSA
levels.Of nutritional factors, increased intake of polysaturated fats and fish in
the routine regimen of PCa cases increased the PSA levels significantly.
CONCLUSIONS: AhR overexpression in PCa pontws to roles of EDCs in PCa but without
any direct association with PSA levels. However, PSA levels are affected by
exposure to possible toxicants in foods whichneed to be assessed as possible risk
factors of PCa in future studies.
PMID- 25124585
TI - Allogeneic hemopietic stem cell transplants for the treatment of B cell acute
lymphocytic leukemia.
AB - OBJECTIVE: Explore the feasibility of allo- hemopietic stem cell transplants in
treating patients with B cell acute lymphocytic leukemia. METHODS: Between
september 2006 and February 2011, fifteen patients with B cell acute lymphocytic
leukemia (ALL) were treated by allo-hemopietic stem cell transplants (HSCT). Stem
cell sources were peripheral blood. Six patients were conditioned by busulfan
(BU) and cyclophosphamide (CY) and nine patients were conditioned with TBI and
cyclophosphamide (CY). Graft versus host disease (GVHD) prophylaxis regimen
consisted of cyclosporine A (CSA), methotrex ate (MTX) and mycophenolatemofetil
(MMF). RESULTS: Patients received a median of 7.98*108.kg-1 (5.36-12.30*108.kg-1)
mononuclear cells (MNC). The median time of ANC>0.5*109/L was day 12 (10-15), and
PLT>20.0*109/L was day 13 (11-16). Extensive acute GVHD occurred in 6 (40.0%)
patients, and extensive chronic GVHD was recorded in 6 (40.0%) patients. Nine
patients were alive after 2.5-65 months follow-up. CONCLUSION: Allogeneic stem
cell transplant could be effective in treating patients with B cell acute
lymphocytic leukemia.
PMID- 25124586
TI - Lack of any association of GST genetic polymorphisms with susceptibility to
ovarian cancer--a meta-analysis.
AB - OBJECTIVE: Epidemiology studies have reported conflicting results between
glutathione S-transferase Mu-1 (GSTM1), glutathione S-transferase theta-1 (GSTT1)
and glutathione S-transferase pi-1 (GSTP1) and ovarian cancer (OC)
susceptibility. In this study, an updated meta-analysis was applied to determine
whether the deletion of GSTM1, GSTT1 and GSTP1 has an influence on OC
susceptibility. METHODS: A published literature search was performed through
PubMed, Embase, Cochrane Library, and Science Citation Index Expanded database
for articles published in English. Pooled odds ratios (ORs) and 95% confidence
intervals (95%CIs) were calculated using random or fixed effects models.
Heterogeneity between studies was assessed using the Cochrane Q test and I2
statistics. Sub-group analysis was conducted to explore the sources of
heterogeneity. Sensitivity analysis was employed to evaluate the respective
influence of each study on the overall estimate. RESULTS: In total, 10 published
studies were included in the final analysis. The combined analysis revealed that
there was no significant association between GSTM1 null genotype and OC risk
(OR=1.01, 95%CI: 0.91-1.12). Additionally, there was no significant association
between GSTT1 genetic polymorphisms and OC risk (OR=0.98, 95% CI: 0.85-1.13).
Similalry, no significant associations were found concerning the GSTP1 rs1695
locus and OC risk. Meanwhile, subgroup analysis did not show a significant
increase in eligible studies with low heterogeneity. However, sensitivity
analysis, publication bias and cumulative analysis demonstrated the reliability
and stability of the current meta-analysis. CONCLUSIONS: These findings suggest
that GSTs genetic polymorphisms may not contribute to OC susceptibility. Large
epidemiological studies with the combination of GSTM1 null, GSTT1 null and GSTP1
Ile105Val polymorphisms and more specific histological subtypes of OC are needed
to prove our findings.
PMID- 25124587
TI - Serum adiponectin but not leptin at diagnosis as a predictor of breast cancer
survival.
AB - Limited numbers of epidemiological studies have examined the relationship between
adipokines and breast cancer survival. Preoperative serum levels of obesity
related adipokines (leptin and adiponectin) were here measured in 370 breast
cancer patients, recruited from two hospitals in Korea. We examined the
association between those adipokines and disease-free survival (DFS). The TNM
stage, ER status and histological grade were aslo assessed in relation to breast
cancer survival. Elevated adiponectin levels were associated with reduced DFS of
breast cancer (Ptrend=0.03) among patients with normal body weight, predominantly
in postmenopausal women. There was no association of leptin with breast cancer
survival. In conclusion, our study suggests that high levels of adiponectin at
diagnosis are associated with breast cancer survival among women with normal body
weight.
PMID- 25124588
TI - Expression of Toll-like receptor 9 increases with progression of cervical
neoplasia in Tunisian women--a comparative analysis of condyloma, cervical
intraepithelial neoplasia and invasive carcinoma.
AB - Toll-like receptors (TLRs) are expressed in immune and tumor cells and recognize
pathogen-associated molecular patterns. Cervical cancer (CC) is directly linked
to a persistent infection with high risk human papillomaviruses (HR-HPVs) and
could be associated with alteration of TLRs expression. TLR9 plays a key role in
the recognition of DNA viruses and better understanding of this signaling pathway
in CC could lead to the development of novel immunotherapeutic approaches. The
present study was undertaken to determine the level of TLR9 expression in
cervical neoplasias from Tunisian women with 53 formalin-fixed and paraffin
embedded specimens, including 22 samples of invasive cervical carcinoma (ICC), 18
of cervical intraepithelial neoplasia (CIN), 7 of condyloma and 6 normal cervical
tissues as control cases. Quantification of TLR9 expression was based on scoring
four degrees of extent and intensity of immunostaining in squamous epithelial
cells. TLR9 expression gradually increased from CIN1 (80% weak intensity) to CIN2
(83.3% moderate), CIN3 (57.1% strong) and ICC (100% very strong). It was absent
in normal cervical tissue and weak in 71.4% of condyloma. The mean scores of TLR9
expression were compared using the Kruskall-Wallis test and there was a
statistical significance between normal tissue and condyloma as well as between
condyloma, CINs and ICC. These results suggest that TLR9 may play a role in
progression of cervical neoplasia in Tunisian patients and could represent a
useful biomarker for malignant transformation of cervical squamous cells.
PMID- 25124589
TI - Prevalence and genotype distribution of HPV among women attending a cervical
cancer screening mobile unit in Lampang, Thailand.
AB - A growing body of literature is evidence that identifying subtypes of high-risk
human papillomavirus (HR-HPV) has impacted on various steps of cervical cancer
prevention.Thus, it is mandatory to determine the background prevalence and
distribution of HPV subtypes for designing and implementing area-specific
management. The present study was conducted to evaluate prevalence and
distribution of HPV subtypes among women aged 30-70 years living in Lampang, an
area with a high incidence of cervical cancer, through use of a mobile screening
unit. Of 2,000 women recruited in this study, 108 (5.40%, 95%CI: 4.45-6.48) were
found to have HR-HPV infection. Risk was significantly correlated with age and
number of partners. Singly or in combination, the most common genotype was HPV 52
(17.6%), followed by HPV 16 (14.81%), HPV 58 (13.89%), HPV 33 (11.11%), HPV 51
(11.11%), and HPV 56 (9.26%). HPV 18 was found in only 5.6% of cases. Together,
HPV 16/18 were noted in approximately 20.4% of cases. Eighteen(16.67%) women were
positive with multiple subtypes of HR-HPV. Co-infection most frequently involved
HPV 16 or HPV 58. These findings have obvious implications for vaccine policy.
PMID- 25124590
TI - Diffusion-weighted imaging for the left hepatic lobe has higher diagnostic
accuracy for malignant focal liver lesions.
AB - BACKGROUND: This study was conducted to investigate whether apparent diffusion
coefficient (ADC) measurements by dividing the liver into left and right hepatic
lobes may be utilized to improve the accuracy of differential diagnosis of benign
and malignant focal liver lesions. MATERIALS AND METHODS: A total of 269
consecutive patients with 429 focal liver lesions were examined by 3-T magnetic
resonance imaging that included diffusion-weighted imaging. For 58 patients with
focal liver lesions of the same etiology in left and right hepatic lobes, ADCs of
normal liver parenchyma and focal liver lesions were calculated and compared
using the paired t-test. For all 269 patients, ADC cutoffs for focal liver
lesions and diagnostic accuracy in the left hepatic lobe, right hepatic lobe and
whole liver were evaluated by receiver operating characteristic curve analysis.
RESULTS: For the group of 58 patients, mean ADCs of normal liver parenchyma and
focal liver lesions in the left hepatic lobe were significantly higher than those
in the right hepatic lobe. For differentiating malignant lesions from benign
lesions in all patients, the sensitivity and specificity were 92.6% and 92.0% in
the left hepatic lobe, 94.4% and 94.4% in the right hepatic lobe, and 90.4% and
94.7% in the whole liver, respectively. The area under the curve of the right
hepatic lobe, but not the left hepatic lobe, was higher than that of the whole
liver. CONCLUSIONS: ADCs of normal liver parenchyma and focal liver lesions in
the left hepatic lobe were significantly higher than those in the right hepatic
lobe. Optimal ADC cutoff for focal liver lesions in the right hepatic lobe, but
not in the left hepatic lobe, had higher diagnostic accuracy compared with that
in the whole liver.
PMID- 25124591
TI - Radiation induces phosphorylation of STAT3 in a dose- and time-dependent manner.
AB - BACKGROUND: We have reported the radiation could activate STAT3, which
subsequently promotes the invasion of A549 cells. We here explored the dose- and
time-response of STAT3 to radiation and the effect of radiation on upstream
signaling molecules. MATERIALS AND METHODS: A549 cells were irradiated with
different doses of gamma-rays. The expression of and nucleus translocation of p
STAT3 in A549 cells were detected by immunoblotting and immunofluorescence,
respectively. The level of phosphorylated EGFR was also assessed by
immunoblotting, and IL-6 expression was detected by real time PCR and ELISA.
RESULTS: Radiation promoted the phosphorylation of STAT3 at Y705 in a dose- and
time-dependent manner and nuclear translocation. The level of phosphorylated EGFR
in A549 cells increased after radiation. In additional, the mRNA and protein
levels of IL-6 in A549 cells were also up regulated by radiation. CONCLUSIONS:
STAT3 is activated by radiation in a dose-and time-dependent manner, probably due
to radiation-induced activation of EGFR or secretion of IL-6 in A549 cells.
PMID- 25124592
TI - Intra-peritoneal cisplatin combined with intravenous paclitaxel in optimally
debulked stage 3 ovarian cancer patients: an Izmir Oncology Group study.
AB - BACKGROUND: The advantage of intra-peritoneal (IP) chemotherapy (CT) in the
initial management of ovarian cancer after cytoreductive surgery is well known.
The feasibility and toxicity of a treatment regimen with an IP+intravenous CT
(IPIVCT) for optimally debulked stage III ovarian cancer were here evaluated
retrospectively. MATERIALS AND METHODS: A total of 30 patients were treated in
our institution between October 2006 and February 2011. Patients received IV
paclitaxel 175 mg/m2 over 3 hours followed by IP cisplatin 75 mg/m2 on day 1;
they also received IP paclitaxel 60 mg/m2 on day 8. They were also scheduled to
receive 6 courses of CT every 21 days. RESULTS: The median age of the patients
was 55 years (35-77), and the majority had papillary serous ovarian cancer
(63.3%). The patients completed a total of 146 cycles of IPIVCT. Twenty-eight
were able to receive at least three cycles of IPIVCT and 18 (60%) completed the
scheduled 6 cycles. Two patients discontinued the IPIVCT because of toxicity of
chemotherapy agents and 6 had to stop treatment due to intolerable abdominal pain
during IP drug administration, obstruction and impaired access. Grade 3/4
toxicities included neutropenia (6 patients; 20%), anemia (2 patients; 6.7%) and
nausea-vomiting (2 patients; 6.7%). Doses were delayed in 12 cycles (8%) for
neutropenia (n=6), thrombocytopenia (n=3) and elevated creatinine (n=3). Drug
doses were not reduced. The median duration of progression-free survival (PFS)
was 47.7 months (95%CI, 38.98-56.44) and overall survival (OS) was 51.7 months
(95%CI, 44.13-59.29). Two and five-year overall survival rates were 75.6 % and
64.8%, respectively. CONCLUSIONS: IPIVCT is feasible and well-tolerated in this
setting. Its clinically proven advantages should be taken into consideration and
more efforts should be made to administer IPIVCT to suitable patients.
PMID- 25124593
TI - In whom do cancer survivors trust online and offline?
AB - BACKGROUND: In order to design effective educational intervention for cancer
survivors, it is necessary to identify most-trusted sources for health-related
information and the amount of attention paid to each source. OBJECTIVE: The
objective of our study was to explore the sources of health information used by
cancer survivors according to their access to the internet and levels of trust in
and attention to those information sources. MATERIALS AND METHODS: We analyzed
sources of health information among cancer survivors using selected questions
adapted from the 2012 Health Information National Trends Survey (HINTS). RESULTS:
Of 357 participants, 239 (67%) had internet access (online survivors) while 118
(33%) did not (offline survivors). Online survivors were younger (p<0.001), more
educated (p<0.001), more non-Hispanic whites (p<0.001), had higher income
(p<0.001), had more populated households (p<0.001) and better quality of life
(p<0.001) compared to offline survivors. Prevalence of some disabilities was
higher among offline survivors including serious difficulties with walking or
climbing stairs (p<0.001), being blind or having severe visual impairment
(p=0.001), problems with making decisions (p<0.001), doing errands alone
(p=0.001) and dressing or bathing (p=0.001). After adjusting for socio-
demographic status, cancer survivors who were non-Hispanic whites (OR=3.49,
p<0.01), younger (OR=4.10, p<0.01), more educated (OR=2.29, p=0.02), with greater
income (OR=4.43, p<0.01), and with very good to excellent quality of life
(OR=2.60, p=0.01) had higher probability of having access to the internet, while
those living in Midwest were less likely to have access (OR=0.177, p<0.01).
Doctors (95.5%) were the most and radio (27.8%) was the least trusted health
related information source among all cancer survivors. Online survivors trusted
internet much more compared to those without access (p<0.001) while offline
cancer survivors trusted health-related information from religious groups and
radio more than those with internet access (p<0.001 and p=0.008). Cancer
survivors paid the most attention to health information on newsletters (63.8%)
and internet (60.2%) and the least to radio (19.6%). More online survivors paid
attention to internet than those without access (68.5% vs 39.1%, p<0.001) while
more offline survivors paid attention to radio compared to those with access
(26.8% vs 16.5%, p=0.03). CONCLUSIONS: Our findings emphasize the importance of
improving the access and empowering the different sources of information.
Considering that the internet and web technologies are continuing to develop,
more attention should be paid to improve access to the internet, provide guidance
and maintain the quality of accredited health information websites. Those without
internet access should continue to receive health-related information via their
most trusted sources.
PMID- 25124594
TI - HPV vaccination for cervical cancer prevention is not cost-effective in Japan.
AB - BACKGROUND: Our study objectives were to evaluate the medical economics of
cervical cancer prevention and thereby contribute to cancer care policy decisions
in Japan. METHODS: Model creation: we created presence- absence models for
prevention by designating human papillomavirus (HPV) vaccination for primary
prevention of cervical cancer. Cost classification and cost estimates: we divided
the costs of cancer care into seven categories (prevention, mass-screening,
curative treatment, palliative care, indirect, non-medical, and psychosocial
cost) and estimated costs for each model. Cost-benefit analyses: we performed
cost-benefit analyses for Japan as a whole. RESULTS: HPV vaccination was
estimated to cost $291.5 million, cervical cancer screening $76.0 million and
curative treatment $12.0 million. The loss due to death was $251.0 million and
the net benefit was -$128.5 million (negative). CONCLUSION: Cervical cancer
prevention was not found to be cost-effective in Japan. While few cost-benefit
analyses have been reported in the field of cancer care, these would be essential
for Japanese policy determination.
PMID- 25124596
TI - Knowledge, perceptions and acceptability of HPV vaccination among medical
students in Chongqing, China.
AB - OBJECTIVES: To evaluate medical students' knowledge of HPV and HPV related
diseases and assess their attitudes towards HPV vaccination. METHODS: A total of
605 medical undergraduates from Chongqing Medical University in China were
surveyed using a structured and pretested questionnaire on HPV related knowledge.
RESULTS: Some 68.9% of the medical students were females, and mean age was 21.6
(+/-1.00) years. Only 10.6% correctly answered more than 11 out of 14 questions
on HPV related knowledge, 71.8% being willing to receive/ advise on HPV
vaccination. Female students (OR: 2.69; 95% CI: 1.53-4.72) and students desiring
more HPV education (OR: 4.24; 95% CI: 1.67-10.8) were more willing to accept HPV
vaccination. HPV vaccination acceptability was observed to show a positive
association with HPV related knowledge. CONCLUSIONS: Our survey found low levels
of HPV related knowledge and HPV vaccination acceptability among participating
medical students. HPV education should be systematically incorporated into
medical education to increase awareness of HPV vaccination.
PMID- 25124595
TI - Lack of associations of the COMT Val158Met polymorphism with risk of endometrial
and ovarian cancer: a pooled analysis of case-control studies.
AB - This meta-analysis was conducted to examine whether the genotype status of
Val158Met polymorphism in catechol-O-methyltransferase (COMT) is associated with
endometrial and ovarian cancer risk. Eligible studies were identified by
searching several databases for relevant reports published before January 1,
2014. Pooled odds ratios (ORs) were appropriately derived from fixed-effects or
random-effects models. In total, 15 studies (1,293 cases and 2,647 controls for
ovarian cancer and 2,174 cases and 2,699 controls for endometrial cancer) were
included in the present meta-analysis. When all studies were pooled into the meta
analysis, there was no evidence for significant association between COMT
Val158Met polymorphism and ovarian cancer risk (Val/Met versus Val/Val: OR=0.91,
95% CI=0.76-1.08; Met/Met versus Val/Val: OR=0.90, 95% CI=0.73-1.10; dominant
model: OR=0.90, 95% CI=0.77-1.06; recessive model: OR=0.95, 95% CI=0.80-1.13).
Similarly, no associations were found in all comparisons for endometrial cancer
(Val/Met versus Val/Val: OR 0.97, 95% CI=0.77-1.21; Met/Met versus Val/Val:
OR=1.02, 95% CI=0.73-1.42; dominant model: OR=0.98, 95% CI=0.77-1.25; recessive
model: OR=1.02, 95% CI=0.87-1.20). In the subgroup analyses by source of control
and ethnicity, no significant associations were found in any subgroup of
population. This meta-analysis strongly suggests that COMT Val158Met polymorphism
is not associated with increased endometrial and ovarian cancer risk.
PMID- 25124597
TI - Pattern of tobacco use and its correlates among older adults in India.
AB - PURPOSE: We examined tobacco use pattern and its correlates among older adults.
MATERIALS AND METHODS: We used data of 9,852 older adults (>=60 years) (men 47%
mean age 68 years) collected by the United Nations Population Fund on Ageing from
seven Indian states. Logistic regression analysis was used to assess the
correlates of tobacco use. RESULTS: Current use of any form of tobacco was
reported by 27.8% (men 37.9%, women 18.8%); 9.2% reported only smoking tobacco,
16.9% smokeless tobacco only and 1.7% used both forms. Alcohol users (OR:5.20,
95% CI:4.06-6.66), men (OR:2.92, CI :2.71-3.47), those reporting lower income
(OR:2.74, CI:2.16- 3.46), rural residents (OR 1.34, CI 1.17-1.54) and lower
castes (OR:1.29, CI:1.13-1.47) were more likely to use any form of tobacco
compared to their counterparts. CONCLUSIONS: Tobacco cessation interventions are
warranted in this population focusing on alcohol users, men, those from lower
income, rural residents and those belonging to a lower caste.
PMID- 25124598
TI - The MMP-2 -735 C allele is a risk factor for susceptibility to breast cancer.
AB - BACKGROUND: The expression of MMP genes has been demonstrated to be associated
with tumor invasion, metastasis and survival rate for a variety of cancers. The
functional promoter polymorphism MMP-2 C-735T is associated with decreased
expression of the MMP-2 gene. The aim of present study was to detect any
association between MMP-2 C-735T and susceptibility to breast cancer. MATERIALS
AND METHODS: The MMP-2 C-735T polymorphism was studied in 233 women (98 with
breast cancer and 135 healthy controls). All studied women were from Kermanshah
and Ilam provinces of Western Iran. The MMP-2 C-735T polymorphism was detected
using a polymerase chain reaction-restriction fragment length polymorphism (PCR
RFLP) method. RESULTS: The frequencies of MMP-2 CC, CT and TT genotypes in
healthy individuals were 59.3, 38.5 and 2.2%, respectively. However, in breast
cancer patients, only CC (71.4%) and CT (28.6%) genotypes were observed
(p=0.077). In patients the frequency of the MMP-2 C allele was significantly
higher (85.7%) compared to that in controls (78.5 %, p=0.048). The presence of C
allele of MMP-2 increased the risk of breast cancer by 1.64-fold [OR=1.64 (95%CI
1.01-2.7, p=0.049)]. The frequency of MMP-2 C allele was also higher in
patients<=40 years (88.9%) than those aged >=41 years (67.5%, p=0.07). In
addition, the frequency of MMP-2 C allele tended to be higher in patients with a
family history of cancer in first-degree relatives (76.6%) compared to that
without a family history of cancer (67.3%, p=0.31). CONCLUSIONS: Our findings
indicate that the C allele of MMP-2 C-735T polymorphism is associated with
increased risk of breast cancer. Also, the MMP-2 C allele might increase the risk
of young onset breast cancer in our population.
PMID- 25124599
TI - Iranian cancer patient perceptions of prognosis and the relationship to hope.
AB - BACKGROUND: The aim of this study was to investigate Iranian cancer patient
perceptions of their prognosis, factors that influence perceptions of prognosis
and the effect this has on patient level of hope. MATERIALS AND METHODS: Iranian
cancer patients (n=200) completed self-report measures of their perceptions of
their prognosis and level of hope, in order to assess the relationship between
the two and identify factors predictive of perceptions by multiple linear
regression analysis. RESULTS: Cancer patients perceived of their prognosis
positively (mean 11.4 out of 15), believed their disease to be curable, and
reported high levels of hope (mean 40.4 out of 48.0). Multiple linear regression
analyses demonstrated that participants who were younger, perceived they had
greater family support, and had higher levels of hope reported more positive
perceptions of their cancer prognosis. CONCLUSIONS: Positive perceptions of
prognosis and its positive correlation with hope in Iranian cancer patients
highlights the importance of cultural issues in the disclosure of cancer related
information.
PMID- 25124600
TI - Associations between AT-rich interactive domain 5B gene polymorphisms and risk of
childhood acute lymphoblastic leukemia: a meta-analysis.
AB - Previous genome-wide association studies (GWAS) have implicated several single
nucleotide polymorphisms (SNPs) in the AT-rich interactive domain 5B (ARID5B)
gene with childhood acute lymphoblastic leukemia (ALL). However, replicated
studies reported some inconsistent results in different populations. Using meta
analysis, we here aimed to clarify the nature of the genetic risks contributed by
the two polymorphisms (rs10994982, rs7089424) for developing childhood ALL.
Through searches of PubMed, EMBASE, and manually searching relevant references, a
total of 14 articles with 16 independent studies were included. Odds ratios (ORs)
with 95% confidence intervals (95%CI) were calculated to assess the associations.
Both SNPs rs10994982 and rs7089424 showed significant associations with childhood
ALL risk in all genetic models after Bonferroni correction. Furthermore, subtype
analyses of B-lineage ALL provided strong evidence that SNP rs10994982 is highly
associated with the risk of developing B-hyperdiploid ALL. These results indicate
that SNPs rs10994982 and rs7089424 are indeed significantly associated with
increased risk of childhood ALL.
PMID- 25124601
TI - Anti-metastasis activity of black rice anthocyanins against breast cancer:
analyses using an ErbB2 positive breast cancer cell line and tumoral xenograft
model.
AB - BACKGROUND: Increasing evidence from animal, epidemiological and clinical
investigations suggest that dietary anthocyanins have potential to prevent
chronic diseases, including cancers. It is also noteworthy that human epidermal
growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene
amplification has been included as an indicator for metastasis and higher risk of
recurrence for breast cancer. MATERIALS AND METHODS: The present experiments
investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on
ErbB2 positive breast cancer cells in vivo and in vitro. RESULTS: Oral
administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth,
inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude
mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The
capacity for migration, adhesion, motility and invasion was also inhibited by
BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by
decreased activity of a transfer promoting factor, urokinase-type plasminogen
activator (u-PA). CONCLUSIONS: Together, our results indicated that BRACs possess
anti-metastasis potential against ErbB2 positive human breast cancer cells in
vivo and in vitro through inhibition of metastasis promoting molecules.
PMID- 25124602
TI - Novel DOX-MTX nanoparticles improve oral SCC clinical outcome by down regulation
of lymph dissemination factor VEGF-C expression in vivo: oral and IV modalities.
AB - BACKGROUND: Oral squamous cell carcinoma (OSCC) remains as one of the most
difficult malignancies to control because of its high propensity for local
invasion and cervical lymph node dissemination. The aim of present study was to
evaluate the efficacy of novel pH and temperature sensitive doxorubicin
methotrexate- loaded nanoparticles (DOX-MTX NP) in terms of their potential to
change the VEGF-C expression profile in a rat OSCC model. MATERIALS AND METHODS:
120 male rats were divided into 8 groups of 15 animals administrated with 4
nitroquinoline-1-oxide to induce OSCCs. Newly formulated doxorubicin-methotrexate
loaded nanoparticles (DOX-MTX NP) and free doxorubicin were IV and orally
administered. RESULTS: RESULTS indicated that both oral and IV forms of DOX-MTX-
nanoparticle complexes caused significant decrease in the mRNA level of VEGF-C
compared to untreated cancerous rats (p<0.05) . Surprisingly, the VEGF-C mRNA was
not affected by free DOX in both IV and oral modalities (p>0.05). Furthermore, in
DOX-MTX NP treated group, less tumors characterized with advanced stage and VEGF
C mRNA level paralleled with improved clinical outcome (p<0.05). In addition,
compared to untreated healthy rats , the VEGF-C expression was not affected in
healthy groups that were treated with IV and oral dosages of nanodrug (p>0.05).
CONCLUSIONS: VEGF-C is one of the main prognosticators for lymph node metastasis
in OSCC. Down-regulation of this lymph-angiogenesis promoting factor is a new
feature acquired in group treated with dual action DOX-MTX-NPs. Beside the
synergic apoptotic properties of concomitant use of DOX and MTX on OSCC, DOX-MTX
NPs possessed anti-angiogenesis properties which was related to the improved
clinical outcome in treated rats. Taking together, we conclude that our
multifunctional doxorubicin-methotrexate complex exerts specific potent apoptotic
and anti-angiogenesis properties that could ameliorate the clinical outcome
presumably via down-regulating dissemination factor-VEGF-C expression in a rat
OSCC model.
PMID- 25124603
TI - Roles for paraoxonase but not ceruloplasmin in peritoneal washing fluid in
differential diagnosis of gynecologic pathologies.
AB - BACKGROUND: Intraperitoneal spread of gynecologic cancers is a major cause of
mortality and morbidity and often presents with malignant ascites. Microscopic
tumor spread can be demonstrated by a peritoneal wash cytology and help assess
the prognosis of the disease. In our study, the roles of paraoxonase and
ceruloplasmin, measured in peritoneal washing fluid of patients operated for
gynecologic pathologies in differential diagnosis was investigated. MATERIALS AND
METHODS: Patients operated for malign or benign gynecologic pathologies in
Antalya Education and Research Hospital Gynecology Clinic between 2010-2012 were
included in the study. Samples were obtained during surgery. RESULTS: A
statistically significant difference was detected between patients with benign
and malign diseases with regards to PON1 levels measured in peritoneal washing
fluid (p:0.044), the average values being 64.2+/-30.8 (Range 10.8-187.2) and
41.4+/-21.4 (Range 10.4-95.5), respectively. No significant variation was evident
for ceruloplasmin. CONCLUSIONS: Paraoxonase levels measured in peritoneal washing
fluid may contribute to the differentiation of malign-benign diseases in
gynecologic pathologies.
PMID- 25124604
TI - Comparison of neutrophil/lymphocyte and platelet/ lymphocyte ratios for
predicting malignant potential of suspicious ovarian masses in gynecology
practice.
AB - PURPOSE: To compare the diagnostic accuracy of the neutrophil/lymphocyte ratio
(NLR) with the platelet/lymphocyte ratio (PLR) in predicting malignancy of pelvic
masses which are pre-operatively malignant suspicious. MATERIALS AND METHODS: In
this retrospective study we evaluated the clinical features of patients with
ovarian masses which had pre-operatively been considered suspicious for
malignancy. The patients whose intraoperative frozen sections were malign were
classified as the study group, while those who had benign masses were the control
group. Data recorded were age of the patient, diameter of the mass, pre-operative
serum Ca 125 levels, platelet count, neutrophil/lymphocyte ratio and
platelet/lymphocyte ratio. RESULTS: There was statistically significantly
difference between the groups in terms of age, diameter of the mass, serum Ca 125
levels, platelet number and platelet/lymphocyte ratio. Mean neutrophil/lymphocyte
ratios showed no difference between the groups. ROC curve analysis showed that
age, serum Ca 125 levels, platelet number and PLR were discriminative markers in
predicting malignancy in adnexal masses. CONCLUSIONS: According to the current
study, serum Ca 125 levels, pre-operative platelet number and PLR may be good
prognostic factors, while NLR is an ineffective marker in predicting the
malignant characteristics of a pelvic mass.
PMID- 25124605
TI - miRNA-1297 induces cell proliferation by targeting phosphatase and tensin homolog
in testicular germ cell tumor cells.
AB - To investigate the role of miR-1297 and the tumor suppressor gene PTEN in cell
proliferation of testicular germ cell tumors (TGCT). MTT assays were used to test
the effect of miR-1297 on proliferation of the NCCIT testicular germ cell tumor
cell line. In NCCIT cells, the expression of PTEN was assessed by Western
blotting further. In order to confirm target association between miR-1297 and 3'
UTR of PTEN, a luciferase reporter activity assay was employed. Moreover, roles
of PTEN in proliferation of NCCIT cells were evaluated by transfection of PTEN
siRNA. Proliferation of NCCIT cells was promoted by miR-1297 in a concentration
dependent manner. In addition, miR-1297 could bind to the 3'-UTR of PTEN based on
luciferase reporter activity assay, and reduced expression of PTEN at protein
level was found. Proliferation of NCCIT cells was significantly enhanced after
knockdown of PTEN by siRNA. miR-1297 as a potential oncogene could induce cell
proliferation by targeting PTEN in NCCIT cells.
PMID- 25124606
TI - Emodin inhibits breast cancer cell proliferation through the ERalpha-MAPK/Akt
cyclin D1/Bcl-2 signaling pathway.
AB - BACKGROUND: The aim of the present study was to investigate the involvement of
emodin on the growth of human breast cancer MCF-7 and MDA-MB-231 cells and the
estrogen (E2) signal pathway in vitro. MATERIALS AND METHODS: MTT assays were
used to detect the effects of emodin on E2 induced proliferation of MCF-7 and MDA
MB-231 cells. Flow cytometry (FCM) was applied to determine the effect of emodin
on E2-induced apoptosis of MCF-7 cells. Western blotting allowed detection of the
effects of emodin on the expression of estrogen receptor alpha, cyclin D1 and B
cell lymphoma-2 (Bcl-2), mitogen-activated protein kinases (MAPK) and
phosphatidylinostiol 3-kinases (PI3K). Luciferase assays were emplyed to assess
transcriptional activity of ERalpha. RESULTS: Emodin could inhibit E2-induced MCF
7 cell proliferation and anti-apoptosis effects, and arrest the cell cycle in
G0/G1 phase, further blocking the effect of E2 on expression and transcriptional
activity of ERalpha. Moreover, Emodin influenced the ER alpha genomic pathway via
downregulation of cyclin D1 and Bcl-2 protein expression, and influenced the non
genomic pathway via decreased PI3K/Akt protein expression. CONCLUSIONS: These
findings indicate that emodin exerts inhibitory effects on MCF-7 cell
proliferation via inhibiting both non-genomic and genomic pathways.
PMID- 25124607
TI - Survival of colorectal cancer patients in the presence of competing-risk.
AB - BACKGROUND: Colorectal cancer (CRC) is considered to be a main cause of
malignancy-related death in the world, being commonly diagnosed in both men and
women. It is the third leading cause of cancer dependent death in the world and
there are one million new cases diagnosed per year. In Iran the incidence of
colorectal cancer has increased during the last 25 years and it is the fifth
cause of cancer in men and the third in women. MATERIALS AND METHODS: In this
article we analyzed the survival of 475 colorectal patients of Taleghani hospital
in Tehran with the semi-parametric competing-risks model. RESULTS: There were 55%
male cases and at the time of the diagnosis most of the patients were between 48
and 67 years old. The probability of a patient death from colorectal cancer with
survival of more than 25 years was about 0.4. Body mass index, height, tumour
site and gender had no influence. CONCLUSIONS: According to these data and by
using semi-parametric competing-risks method, we found out that only age at
diagnosis has a significant effect on these patient survival time.
PMID- 25124608
TI - Development of in-house multiplex real time PCR for human papillomavirus
genotyping in Iranian women with cervical cancer and cervical intraepithelial
neoplasia.
AB - BACKGROUND: HPV related cervical cancer as one of the most common women cancers
in developing countries. Regarding accessibility of commercial vaccines, any long
or short term modality for integrating preventive immunization against HPV in a
national program needs comprehensive information about HPV prevalence and its
genotypes. The important role of selecting most accurate diagnostic technologies
for obtaining relevant data is underlined by different assays proposed in the
literature. The main objective of the present study was to introduce an in-house
HPV typing assay using multiplex real time PCR with reliable results and
affordable cost for molecular epidemiology surveys and diagnosis. MATERIALS AND
METHODS: 112 samples of formalin fixed paraffin embedded tissues and liquid based
cytology specimens from patients with known different grades of cervical
dysplasia and invasive cancer, were examined by this method and the result were
verified by WHO HPV LabNet proficiency program in 2013. RESULTS: HPV was detected
in 105 (93.7%) out of 112 samples. The dominant types were HPV 18 (61.6%) and HPV
16 (42.9%). Among the mixed genotypes, HPV 16 and 18 in combination were seen in
12.4% of specimens. CONCLUSIONS: According to acceptable performance, easy access
to primers, probes and other consumables, affordable cost per test, this method
can be used as a diagnostic assay in molecular laboratories and for further
planning of cervical carcinoma prevention programs.
PMID- 25124609
TI - Timing of thoracic radiotherapy in limited stage small cell lung cancer: results
of early versus late irradiation from a single institution in Turkey.
AB - BACKGROUND: It is standard treatment to combine chemotherapy (CT) and thoracic
radiotherapy (TRT) in treating patients with limited stage small cell lung cancer
(LS-SCLC). However, optimal timing of TRT is unclear. We here evaluated the
survival impact of early versus late TRT in patients with LS-SCLC. MATERIALS AND
METHODS: Follow-up was retrospectively analyzed for seventy consecutive LS-SCLC
patients who had successfully completed chemo-TRT between January 2006 and
January 2012. Patients received TRT after either 1 to 2 cycles of CT (early TRT)
or after 3 to 6 cycles of CT (late TRT). Survival and response rates were
evaluated using the Kaplan-Meier method and comparisons were made using the
multivariate Cox regression test. RESULTS: Median follow-up was 24 (5 to 57)
months. Carboplatin+etoposide was the most frequent induction CT (59%). Median
overall, disease free, and metastasis free survivals in all patients were 15 (5
to 57), 5 (0 to 48) and 11 (3 to 57) months respectively. Late TRT was superior
to early TRT group in terms of response rate (p=0.05). 3 year overall survival
(OS) rates in late versus early TRT groups were 31% versus 17%, respectively
(p=0.03). Early TRT (p=0.03), and incomplete response to TRT (p=0.004) were
negative predictors of OS. Significant positive prognostic factors for distant
metastasis free survival were late TRT (p=0.03), and use of PCI (p=0.01). Use of
carboplatin versus cisplatin for induction CT had no significant impact on OS
(p=0.634), DFS (p=0.727), and MFS (p=0.309). CONCLUSIONS: Late TRT appeared to be
superior to early TRT in LS-SCLC treatment in terms of complete response, OS and
DMFS. Carboplatin or cisplatin can be combined with etoposide in the induction CT
owing to similar survival outcomes.
PMID- 25124610
TI - MiR-150-5p suppresses colorectal cancer cell migration and invasion through
targeting MUC4.
AB - Growing evidence suggests that miR-150-5p has an important role in regulating
genesis of various types of cancer. However, the roles and the underlying
mechanisms of miR-150-5p in development of colorectal cancer (CRC) remain largely
unknown. Transwell chambers were used to analyze effects on cell migration and
invasion by miR-150-5p. Quantitative real-time PCR (qRT-PCR), Western blotting
and dual-luciferase 3' UTR reporter assay were carried out to identify the target
genes of miR-150-5p. In our research, miR-150-5p suppressed CRC cell migration
and invasion, and MUC4 was identified as a direct target gene. Its effects were
partly blocked by re-expression of MUC4. In conclusiomn, miR-150-5p may suppress
CRC metastasis through directly targeting MUC4, highlighting its potential as a
novel agent for the treatment of CRC metastasis.
PMID- 25124611
TI - Efficacy and tolerance of pegaspargase-based chemotherapy in patients with nasal
type extranodal NK/T-cell lymphoma: a pilot study.
AB - Nasal-type extranodal natural killer (NK)/T-cell lymphoma (ENKL) is a highly
invasive cancer with a poor prognosis. More effective and safer treatment
regimens for ENKL are needed. Pegaspargase (PEG-Asp) has a similar mechanism of
action to L-asparaginase (L-Asp), but presents lower antigenicity. The aim of the
present research was to evaluate the safety profile and the latent efficacy of a
PEG-Asp-based treatment regimen in patients with ENKL. Data collected from 20
patients with histologically confirmed ENKL, admitted to the Third Affiliated
Hospital of Sun Yat-Sen University from January 2009 to August 2013, were
included in the study. All patients received 2500 IU/m2/IM PEG-Asp on day 1 of
every 21-day treatment cycle. Patients received combination chemotherapy with
CHOP (n=5), EPOCH (n=7), GEMOX (n=7) or CHOP with bleomycin (n=1). After 2-5
treatment cycles (median, 4 cycles) of PEG-Asp-based chemotherapy, five patients
(25%) showed a complete response (CR), and the overall response rate (ORR) was
60%. Grade 3/4 neutropenia occurred in fourteen patients (70%). Grade 3 alanine
aminotransferase (ALT) elevation was observed in two. Grade 1-2 non-hematological
toxicity consisted of activated partial thromboplastin time (APTT) elongation
(n=9), hypofibrinogenemia (n=6), hypoproteinemia (n=17), hyperglycemia (n=3), and
nausea (n=6). No allergic reactions were detected. No treatment related death was
reported. Our results suggested that PEG-Asp-based chemotherapy presented an
acceptable tolerance and a potential short-term outcome in patients with nasal
type ENKL.
PMID- 25124612
TI - Identification of patients with microscopic hematuria who are at greater risk for
the presence of bladder tumors using a dedicated questionnaire and point of care
urine test--a study by the members of Association of Urooncology, Turkey.
AB - In patients with microscopic hematuria there is a need for better identification
of those who are at greater risk of harbouring bladder tumors. The RisikoCheck(r)
questionnaire has a strong correlation with the presence of urothelial carcinoma
(UC) of the bladder and in combination with other available tests may help
identify patients who require detailed clinical investigations due to increased
risk of presence of bladder tumors. This study aimed to evaluate the efficacy of
RisikoCheck(r) questionnaire together with NMP-22(r) (BladderChek(r)) as a point
of-care urine test in predicting the presence of bladder tumors in patients
presenting with microscopic hematuria as the sole finding. In this multi
institutional prospective evaluation of 303 consecutive patients without a
history of urothelial carcinoma (UC), RisikoCheck(r) risk group assessment,
urinary tract imaging and cystourethroscopy as well as urine cytology and Nuclear
Matrix Protein-22 (NMP-22 BladderChek) testing were performed where available.
The sensitivity, specificity, negative predictive value (NPV), and positive
predictive values (PPV) for the risk adapted approach were calculated. All
patients underwent cystoscopy, and tumors were detected in 18 (5.9%). Urine
cytology and NMP-22 was positive for malignancy in 9 (3.2%) and 12 (7.5%) of
patients, respectively. A total of 43 (14%) patients were in the high risk group
according to the RisikoCheck(r) questionnaire. The sensitivity and specificity of
the questionnaire in detecting a bladder tumor was 61.5 % and 84.0 % in the high
risk group. In patients with either a positive NMP-22 test or high risk category
RisikoCheck(r), 23.6% had bladder tumors with a corresponding sensitivity of
54.2% and specificity of 88.6%. If both tests were negative only 3.3% of the
patients had bladder tumors. The results of our study suggest that the efficacy
of diagnostic evaluation of patients with microscopic hematuria may be further
enhanced by combining RisikoCheck(r) questionnaire with NMP-22.
PMID- 25124613
TI - Effect of lymphangiogenesis and lymphovascular invasion on the survival pattern
of breast cancer patients.
AB - BACKGROUND: Invasion of breast cancer cells into blood and lymphatic vessels is
one of the most important steps for metastasis. In this study the prognostic
relevance of lymphangiogenesis and lymphovascular invasion (LVI) in breast cancer
patients was evaluated in terms of survival. MATERIALS AND METHODS: This
retrospective study concerned 518 breast cancer patients who were treated at
Department of Surgical Oncology, Saroj Gupta Cancer Centre and Research
Institute, Kolkata-700063, West Bengal, India, a reputed cancer centre and
research institute of eastern India between January 2006 and December 2007.
RESULTS: The median overall survival and disease free survival of the patients
were 60 months and 54 months respectively. As per Log-rank test, poor overall as
well as disease free survival pattern was observed for LVI positive patients as
compared with LVI negative patients (p<0.01). Also poor overall as well as
disease free survival pattern was observed for perineural invasion (PNI) positive
patients as compared to PNI negative patients (p<0.01). CONCLUSIONS: From this
study it is evident that LVI and PNI are strongly associated with outcome in
terms of disease free as well as overall survival in breast cancer patients. Thus
LVI and PNI constitute potential targets for treatment of breast cancer patients.
We advocate incorporating their status into breast cancer staging systems.
PMID- 25124614
TI - Combined detection of CEA, CA 19-9, CA 242 and CA 50 in the diagnosis and
prognosis of resectable gastric cancer.
AB - Our aim was to investigate the value of combined detection of serum
carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, CA 242 and CA 50
in diagnosis and assessment of prognosis in consecutive gastric cancer patients.
Clinical data including preoperative serum CEA, CA 19-9, CA 242, and CA 50 values
and information on clinical pathological factors were collected and analyzed
retrospectively. Univariate and multivariate survival analyses were used to
explore the relationship between tumor markers and survival. Positive rates of
tumor markers CEA, CA 19-9, CA 242 and CA 50 in the diagnosis of gastric cancer
were 17.7, 17.1, 20.4 and 13.8%, respectively, and the positive rate for all four
markers combined was 36.6%. Patients with elevated preoperative serum
concentrations of CEA, CA 19-9, CA 242 and CA 50, had late clinical tumor stage
and significantly poorer overall survival. Five-year survival rates in patients
with elevated CEA, CA 19-9, CA 242 and CA 50 were 28.1, 25.8, 27.0 and 24.1%,
respectively, compared with 55.0, 55.4, 56.4 and 54.5% in patients with these
markers at normal levels (p<0.01). In multivariate Cox proportional hazards
analyses, an elevated CA 242 level was determined to be an independent prognostic
marker in gastric cancer patients. Combined detection of four tumor markers
increased the positive rate for gastric cancer diagnosis. CA 242 showed higher
diagnostic value and CA 50 showed lower diagnostic value. In resectable gastric
carcinoma, preoperative CA 242 level was associated with disease stage, and was
found to be a significant independent prognostic marker in gastric cancer
patients.
PMID- 25124615
TI - Preliminary evaluation of the in vitro efficacy of 1, 2-di (quinazolin-4-yl)
diselane against SiHa cervical cancer cells.
AB - Cervical cancer is one the most common malignancies among females. In recent
years, its incidence rate has shown a rising trend in some countries so that
development of anticancer drugs for cervical cancer is an urgent priority. In our
recent anticancer drug discovery screen, 1, 2-di (quinazolin-4-yl)diselane
(LG003) was found to possess wide spectrum anticancer efficacy. In the present
work, the in vitro anticancer activity of LG003 was evaluated in the SiHa
cervical cancer cell line. Compared with commercial anticancer drugs 10
hydroxycamptothecin, epirubicin hydrochloride, taxol and oxaliplatin, LG003
showed better anticancer activity. Furthermore, inhibition effects were time- and
dose-dependent. Morphological observation exhibited LG003 treatment results in
apoptosis like shrinking and blebbing, and cell membrane damage. Lactate
dehydrogenase release assay revealed that LG003 exerts such effects in SiHa cells
through a physiology pathway rather than cytotoxicity, which suggests that title
compound LG003 can be a potential candidate agent for cervical cancer.
PMID- 25124616
TI - Are women in Kuwait aware of breast cancer and its diagnostic procedures?
AB - The aim of this study was to examine the knowledge and awareness of women in
Kuwait with regard to risk factors, symptoms and diagnostic procedures of breast
cancer. A total of 521 questionnaires were distributed among women in Kuwait.
Results showed that 72% of respondents linked breast cancer factors to family
history, while 69.7% scored abnormal breast enlargement as the most detectable
symptom of the disease. Some 84% of participants had heard about self
examination, but knowledge about mammograms was limited to 48.6% and only 22.2%
were familiar with diagnostic procedures. Some 22.9% of respondents identified
the age over 40 years as the reasonable age to start mammogram screening. Risk
factor awareness was independent on age groups (p>0.05), but both high education
and family history increased the likelihood of postivie answers; the majority
knew about a few factors such as aging, pregnancy after age 30, breast feeding
for short time, menopause after age of 50, early puberty, and poor personal
hygiene. In conclusion, 43.1% of participants had an overall good knowledge of
breast cancer with regards to symptoms, risk factors and breast examination. Very
highly significant associations (p<0.005) were evident for all groups except for
respondents distributed by nationality (p=0.444). Early campaigns for screening
the breast should be recommended to eliminate the confusion of wrong perceptions
about malignant mammary disease.
PMID- 25124617
TI - Expression of neuronal markers, NFP and GFAP, in malignant astrocytoma.
AB - BACKGROUND: Immunohistochemical markers are considered as important factors in
diagnosis of malignant astrocytomas. The aim of the current study was to
investigate the frequency of the immunohistochemical markers neurofilament
protein (NFP) and glial fibrillary acidic protein (GFAP) in malignant astrocytoma
tumors in Firoozgar and Rasool-Akram hospitals from 2005 to 2010. MATERIALS AND
METHODS: In this cross-sectional study, immunohistochemical analysis of NFP and
GFAP was performed on 79 tissue samples of patients with the diagnosis of
anaplastic and glioblastoma multiform (GBM) astrocytomas. RESULTS: The obtained
results demonstrated that all patients were positive for GFAP and only 3.8% were
positive for NFP. There was no significant association between these markers and
clinical, demographic, and prognostic features of patients (p>0.05). CONCLUSIONS:
NFP was expressed only in GBMs and not in anaplastic astrocytomas. It would be
crucial to confirm the present findings in a larger number of tumors, especially
in high grade gliomas.
PMID- 25124618
TI - Activation of JNK/p38 pathway is responsible for alpha-methyl-n-butylshikonin
induced mitochondria-dependent apoptosis in SW620 human colorectal cancer cells.
AB - alpha-Methyl-n-butylshikonin (MBS), one of the active components in the root
extracts of Lithospermum erythrorhizon, posses antitumor activity. In this study,
we assess the molecular mechanisms of MBS in causing apoptosis of SW620 cells.
MBS reduced the cell viability of SW620 cells in a dose-and time-dependent manner
and induced cell apoptosis. Treatment of SW620 cells with MBS down-regulated the
expression of Bcl-2 and up-regulated the expression of Bak and caused the loss of
mitochondrial membrane potential. Additionally, MBS treatment led to activation
of caspase-9, caspase-8 and caspase-3, and cleavage of PARP, which was abolished
by pretreatment with the pan-caspase inhibitor Z-VAD-FMK. MBS also induced
significant elevation in the phosphorylation of JNK and p38. Pretreatment of
SW620 cells with specific inhibitors of JNK (SP600125) and p38 (SB203580)
abrogated MBS-induced apoptosis. Our results demonstrated that MBS inhibited
growth of colorectal cancer SW620 cells by inducing JNK and p38 signaling
pathway, and provided a clue for preclinical and clinical evaluation of MBS for
colorectal cancer therapy.
PMID- 25124619
TI - Patterns and trends with cancer incidence and mortality rates reported by the
China National Cancer Registry.
AB - National cancer registration reports provide a huge potential for identifying
patterns and trends of important policy, research, prevention and treatment
significance. As summary reports written on an annual basis, the China Cancer
Registry Annual Reports (CCRARs) fall short from fully addressing their
potential. This paper attempts to explore part of the patterns and trends hidden
behind published CCRARs. It extracted data for cancer incidence rates (IRs) and
mortality rates (MRs) for 2004, 2006 and 2009 from relevant CCRARs and portrayed
4 kinds of indicators in line graphs. The study showed that: a) all of the line
graphs of age-specific IRs and MRs characterized typical "growth curves or
histogram"; b) graphs of IRs and MRs for males and urban areas had higher peaks
than that for females and rural regions; c) most of the line graphs of IR/MR
ratios comprised a starting peak, a secondary peak and a decreasing tail and the
secondary peaks for females and urban areas were higher than those for males and
rural areas; d) most of the urban versus rural IR ratios valued above one, but
most the urban versus rural MR ratios, below one; e) the accumulative IRs and MRs
showed a stable increasing trend from 2004 to 2009 for urban areas, but mixed for
rural regions.
PMID- 25124620
TI - Lack of association between the MTHFRC677T polymorphism and lung cancer in a
Turkish population.
AB - BACKGROUND: In this case-control study, we aimed to investigate the relationship
between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and
lung cancer. MATERIALS AND METHODS: Total 200 individuals including 100 patients
with lung cancer and 100 controls were analyzed. Genotyping of MTHFR C677T was
performed using PCR and RFLP methods. RESULTS: The majority of the patients were
men and 90% were smokers. We found that the risk ratio for development of LC was
13-times higher in smokers compared with non-smokers between patient and control
groups in our study (OR:13.5, 95%CI:6.27-29.04, p:0.0001). Besides, the risk
ratio for development of LC was nine times higher in individuals with cancer
history in their family than those without cancer history (OR:9.65, 95%CI: 2.79
33.36; p:0.0001). When genotype distributions and allele frequencies were
analyzed in the study groups, no significant difference was apparent (chi2:0.53,
p=0.76). In addition, no correlation between genotypes of MTHFRC677T polymorphism
and histological type of LC was found (chi2:0.99, p=0.60). CONCLUSIONS: These
results suggest that there was no association between the MTHFR C677T
polymorphism and lung cancer in the Turkish population.
PMID- 25124621
TI - Outcome of rectal cancer in patients aged 30 years or less in the Pakistani
population.
AB - BACKGROUND: The incidence of rectal cancer is increasing in younger age groups.
Limited data is available regarding survival outcome in younger patients with
conflicting results from western world. The goal of this study was to determine
survival in patients with rectal cancer<30 years of age and compare it with their
older counterparts in the Pakistani population. MATERIALS AND METHODS: A
retrospective chart review of patients operated for rectal adenocarcinoma between
January 2005 and December 2010 was performed. Patients were divided into two
groups, Group 1 aged <=30 years and Group 2 aged >30 years. Patient
characteristics, surgical procedure, histopathological details and number of loco
regional and distant failures were compared. Expected 5 year survival was
calculated using Kaplan Meier curves and significance was determined using the
Log rank test. RESULTS: There were 38 patients in group 1 and 144 in group 2. A
significantly high number of younger patients presented with poorly
differentiated histology (44.7% vs 9.7%) (p=0.0001) and advanced pathological
stage (63.1% vs 38.1%) (p=0.04). Predicted overall 5 year survival was 38% versus
57% in groups I and II, respectively (p=0.05). Disease free survival was 37%
versus 52% and was significantly different (p=0.007). CONCLUSIONS: Early onset
rectal cancer is associated with poor pathological features and a worse outcome
in Pakistani population.
PMID- 25124622
TI - Preparation and antitumor activity of a tamibarotene-furoxan derivative.
AB - Multi-target drug design, in which drugs are designed as single molecules to
simultaneously modulate multiple physiological targets, is an important strategy
in the field of drug discovery. QT-011, a tamibarotene-furoxan derivative, was
here prepared and proposed to exert synergistic effects on antileukemia by
releasing nitric oxide and tamibarotene. Compared with tamibarotene itself, QT
011 displayed stronger antiproliferative effects on U937 and HL-60 cells and was
more effective evaluated in a nude mice U937 xenograft model in vivo. In
addition, QT-011 could release nitric oxide which might contribute to the
antiproliferative activity. Autodocking assays showed that QT-011 fits well with
the hydrophobic pocket of retinoic acid receptors. Taken together, these results
suggest that QT-011 might be a highly effective derivative of tamibarotene and a
potential candidate compound as antileukemia agent.
PMID- 25124623
TI - Insulin promotes proliferation and migration of breast cancer cells through the
extracellular regulated kinase pathway.
AB - The present study was undertaken to determine the roles of insulin in the growth
of transplanted breast cancer in nude mice, and the proliferation and migration
of MCF-7 human breast cancer cells and assess its influence on downstream
signaling pathways. In a xenograft mouse model with injection of MCF-7 human
breast cancer cells, tumor size was measured every other day. The insulin level
and insulin receptor (IR) were increased in the breast cancer patient tissues.
Insulin injected subcutaneously around the tumor site in mice caused increase in
the size and weight of tumor masses, and promoted proliferation and migration of
MCF-7 cells. The effects of insulin on the increase in the proliferation and
migration of MCF-7 human breast cancer cells were abolished by pretreatment with
the extracellular regulated kinase (ERK) inhibitor PD98059. Insulin increased the
phosphorylation of ERK in the MCF-7 cells. These results indicate that insulin
promotes the growth of breast cancer in nude mice, and increases the
proliferation and migration of MCF-7 human breast cancer cells via the ERK
pathway.
PMID- 25124624
TI - Risk factors of lymph node metastases with endometrial carcinoma.
AB - BACKGROUND: The purpose of this study was to investigate and evaluate risk
factors for lymph node metastases (LNM) in cases of endometrial cancer (EC).
MATERIALS AND METHODS: A retrospective single institution analysis of patients
surgically staged for EC at Ankara Oncology Education and Research Hospital from
1996 to 2010 was performed. Roles of prognostic factors, such as age,
histological type, grade, depth of myometrial invasion, cervical involvement,
peritoneal cytology, and tumor size, in the prediction of LNM were evaluated.
Fisher's exact test and logistic regression analysis were used to assess the
effects of various factors on LNM. RESULTS: LNM was observed in 22 out of 247
patients (8.9%) and was significantly more common in the presence of tumors of
higher grade, deep myometrial invasion (DMI), cervical involvement, size>2 cm,
and with positive peritoneal cytology. Logistic regression analysis revealed that
DMI remained the only independent risk factor for LNM. NPV, PPV, sensitivity, and
specificity for satisfying LNM risk were 98.0, 19.5, 86.3, and 65.3%,
respectively for DMI. CONCLUSIONS: The incidence of LNM is influenced
independently by DMI. If data support a conclusion of DMI, LND should be
seriously considered.
PMID- 25124625
TI - Cancers of the young population in Brunei Darussalam.
AB - BACKGROUND: Globally, the overall incidence of cancer is increasing as a result
of ageing populations and changing lifestyles. Cancer is one of the leading
causes of death, especially in the developed nations. Cancers affecting the young
population are generally considered uncommon. This study assessed the demography
and trends of cancers of the young in Brunei Darussalam, a small and developing
Southeast Asia nation. MATERIALS AND METHODS: All patients diagnosed with cancers
between 2000 and 2012 were identified from the cancer registry maintained by the
State Histopathology Laboratory. Cancers of the young was defined as any cancers
diagnosed under the age of 40 years. Demographic data and the type of cancers
were collected and analysed using SPSS Statistics 17.0. RESULTS: Among the 6,460
patients diagnosed with cancer over the study period, 18.7% (n=1,205) were
categorized as young with an overall decline in the proportion from 26.6% in 2000
to 18.8% in 2012 (p<0.001 for trend). Among all cancers of the young, the most
common systems affected were gynecological (24.1%), hematological/lymphatic
(15.8%), subcutaneous/dermatological/ musculoskeletal (10.5%), breast (10.5%) and
gastrointestinal (9.9%). Overall, among the different systems, neurological
(54.9%) had the highest proportion of cancers of the young followed by
gynecological/reproductive (30.6%), hematological/ lymphatic (39.9%), endocrine
(38.7%), subcutaneous/dermatological/ musculoskeletal (22.3%) and the head and
neck region (20.1%). There was a female predominance (66.9%) and the incidence
was significantly higher among the Malays (20.1%) and expatriates (25.1%) groups
compared to the Chinese (10.7%) and indigenous (16.8%) groups (p<0.001 for
trend). CONCLUSIONS: Cancers of the young (<40 years) accounted for almost a
fifth of all cancers in Brunei Darussalam with certain organ systems more
strongly affected. There was a female preponderance in all racial groups. Over
the years, there has been a decline in the overall proportion of cancers of the
young. Selective screening programs should nevertheless be considered.
PMID- 25124626
TI - Preventive effect of Actinidia valvata Dunn extract on N-methyl-N'-nitro-N
nitrosoguanidine-induced gastrointestinal cancer in rats.
AB - PURPOSE: This study was conducted to assess the preventive effect of Actinidia
valvata Dunn (AVD) extract on an animal model of gastrointestinal carcinogenesis
on the basis of changes in tumor incidence, cell proliferation, and apoptosis.
MATERIALS AND METHODS: Seventy-five male Wistar rats were divided into five
different treatment groups with 15 rats in each group. Group I was given normal
feed, whereas Groups II to IV were treated with 10% sodium chloride in the first
six weeks and 100 ug/mL of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in
drinking water for 24 weeks. Group II was then given normal feed, whereas Group
III was given AVD extract (0.24 g/kg/day) for 12 weeks. Group IV was given AVD
extract from the first week to the 36th week, whereas Group V was treated with
AVD extract alone for 36 weeks. All rats were sacrificed at the end of the 36
week experiment and assessed for the presence of gastrointestinal tumors. The
occurrence of cancer was evaluated by histology. Bax, Bcl-2, Caspase-3, and
cyclinD1 were determined by immunohistochemical staining and Western blotting.
RESULTS: The incidences of gastric cancer were 0% in Group I, 73.3% in Group II,
33.3% in Group III, 26.7% in Group IV, and 0% in Group V. Bcl-2 and cyclinD1
expression was decreased in AVD extract treated groups, whereas Bax and Caspase-3
expression was increased. Comparison with group II revealed significant
differences (p<0.01). CONCLUSIONS: AVD extract exhibits an obvious preventive
effect on gastrointestinal carcinogenesis induced by MNNG in rats through the
regulation of cell proliferation and apoptosis.
PMID- 25124627
TI - Circulating tumor cells are associated with bone metastasis of lung cancer.
AB - Lung cancer (LC) is the leading cause of cancer mortality worldwide,
predominantly due to the difficulty of early diagnosis and its high metastatic
potential. Recently, increasing evidence suggests that circulating tumour cells
(CTCs) are responsible for cancer metastatic relapse, and CTCs have attracted
interest in cancer metastasis detection and quantification. In present study, we
collected blood samples from 67 patients with bone metastasis, and 30 patients
without such metastasis, and searched for CTCs. Then the association of CTC
numbers with bone metastasis and other clinico-pothological variants was
analyzed. Results demonstrated that when 5 or 1 was taken as a threshhold for the
CTC number, there were significantly higher positivity of CTCs in the bone
metastasis group than in the non-metastasis group. While the increase in CTC
number was not significantly associated with any other clinicopathological
factor, including age, gender, pathological type, intrapulmonary metastasis and
lymph node metastasis, the CTC number in patients with positivity of the last
above mentioned variants was obviously higher than in patients with negativity of
the two variants. Taken together, the CTC number appears to be significantly
associated with the bone metastasis from lung cancer.
PMID- 25124629
TI - Descriptive report on pattern of variation in cancer cases within selected ethnic
groups in Kamrup Urban District of Assam, 2009-2011.
AB - BACKGROUND: The global burden of cancer is continuously increasing. According to
recent report of the National Cancer Registry Programme (NCRP) on time trends it
is estimated that future burden of cancer cases for India in 2020 will be
1,320,928. It is well known that knowledge of the incidence of cancer is a
fundamental requirement of rational planning and monitoring of cancer control
programs. It would help health planners to formulate public health policy if
relevant ethnic groups were considered. North East-India alone contains over 160
Scheduled Tribes and 400 other sub-tribal communities and groups, whose cancer
incidence rates are high compared to mainland India. As since no previous study
was done focusing on ethnicity, the present investigation was performed.
MATERIALS AND METHODS: In this paper PBCR-Guwahati data on all cancer
registrations from January 2009 to December 2011 for residents of the Kamrup
Urban District, comprising an area of 261.8 sq. km with a total population of
900,518, including individual records with information on sex, age, ethnicity and
cancer site are provided. Descriptive statistics including age adjusted rates
(AARs) were taken as provided by NCRP. For comparison of proportional incidence
ratios (PIR) the Student's t test was used, with p<0.05 considered as
statistically significant. RESULTS AND CONCLUSIONS: Differences in leading sites
of Kamrup Urban District since from the beginning of the PBCR-Guwahati were
revealed among different ethnic groups by this study. The results should help
policy makers to formulate different strategies to control the level of burden as
well as for treatment planning. This study also suggests that age is an important
factor of cancer among different ethnic populations as well as for overall
population of Kamrup District of Assam.
PMID- 25124628
TI - Is the neutrophil-lymphocyte ratio an indicator of progression in patients with
benign prostatic hyperplasia?
AB - PURPOSE: The aim of this study was to evaluate inflammation parameters and assess
the utility of the neutrophil- lymphocyte ratio (NLR) as a simple and readily
available predictor for clinical disease activity in patients with nenign
prostate hyperplasia BPH. We also aimed to investigate the relationship between
inflammatory parameters with alpha-blocker therapy response, and evaluate the
potential association between NLR and the progression of benign prostatic
hyperplasia (BPH). MATERIALS AND METHODS: We examined 320 consecutive patients
(July 2013-December 2013) admitted to our outpatient clinic with symptoms of the
lower urinary tract at Bozok University. The mean age was 60 (range, 51-75)
years. Complete blood count (CBC), prostate-specific antigen (PSA), erythrocyte
sedimentation rate (ESR), and C-reactive protein (CRP) were assessed.
Correlations between PSA, CRP, ESR, prostate volume, International Prostate
Symptom Score (IPPS), maximum urinary flow rate (Qmax), and NLR were assessed
statistically. Patients were divided into two groups: high and low risk of
progression. RESULTS: NLR was positively correlated with IPSS (p=0.001, r=0.265),
PSA (p=0.001, r=0.194), and negatively correlated with Qmax (p<0.001, r=-0.236).
High-risk patients a had a higher NLR compared with low-risk patients, based on
IPSS (p<0.001), PSA (p=0.013), and Qmax (p<0.001); however, there were no
significant differences between the groups in terms of age (p>0.05), and prostate
volume (p>0.05). CONCLUSIONS: NLR can predict BPH progression. We propose that
increased inflammation is negatively associated with clinical status in BPH
patients and suggest that NLR can give information along with LUTS severity which
may be used as a readikly accessible marker for patient follow-up.
PMID- 25124630
TI - Prognostic significance of the peripheral blood absolute monocyte count in
patients with locally advanced or metastatic hepatocellular carcinoma receiving
systemic chemotherapy.
AB - BACKGROUND: The prognostic significance of the circulating absolute monocyte
count (AMC) in patients with locally advanced hepatocellular carcinoma (HCC) is
uncertain. This study was designed to assess the association of circulating AMC
with survival outcomes in patients diagnosed with locally advanced or metastatic
HCC receiving systemic chemotherapy. MATERIALS AND METHODS: Between January 1,
2005 and December 30, 2012, locally advanced or metastatic HCC patients who had
Child-Pugh stage A or B disease and received systemic chemotherapy were
retrospectively enrolled. Patient features including gender, age, extrahepatic
metastasis, Child-Pugh stage, serum alpha-fetoprotein(AFP) level and AMC were
collected to investigate their prognostic impact on overall survival(OS).
RESULTS: A total of 216 patients were eligible for the study. The optimal cut-off
value of AMC for OS analysis was 0.38*109/L. Median OS was 5.84 months in low-AMC
group (95% confidence interval [CI], 5.23 to 6.45), and 5.21 months in high-AMC
group (95% CI, 4.37 to 6.04; p=0.003). In COX multivariate analysis, elevated AMC
remained as an independent prognostic factor for worse OS (HR, 1.578; 95% CI,
1.120 to 2.223, p=0.009). CONCLUSIONS: Our results indiicate that circulating AMC
is confirmed to be an independent prognostic factor for OS in patients with
locally advanced or metastatic HCC receiving systemic chemotherapy.
PMID- 25124631
TI - Aquaporin 8 involvement in human cervical cancer SiHa migration via the EGFR
Erk1/2 pathway.
AB - Overexpression of aquaporins (AQPs) has been reported in several human cancers.
Epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinases
1/2 (Erk1/2) are associated with tumorigenesis and cancer progression and may
upregulate AQP expression. In this study, we demonstrated that EGF (epidermal
growth factor) induces SiHa cells migration and AQP8 expression. Wound healing
results showed that cell migration was increased by 2.79-1.50-fold at 24 h and 48
h after EGF treatment. AQP8 expression was significantly increased (3.33-fold) at
48 h after EGF treatment in SiHa cells. An EGFR kinase inhibitor, PD153035,
blocked EGF-induced AQP8 expression and cell migration and AQP8 expression was
decreased from 1.59-fold (EGF-treated) to 0.43-fold (PD153035-treated) in SiHa.
Furthermore, the MEK (MAPK (mitogen-activated protein kinase)/Erk (extracellular
signal regulated kinase)/Erk inhibitor U0126 also inhibited EGF-induced AQP8
expression and cell migration. AQP8 expression was decreased from 1.21-fold (EGF
treated) to 0.43-fold (U0126-treated). Immunofluorescence microscopy further
confirmed the results. Collectively, our findings show that EGF induces AQP8
expression and cell migration in human cervical cancer SiHa cells via the
EGFR/Erk1/2 signal transduction pathway.
PMID- 25124632
TI - Loss of expression and aberrant methylation of the CDH1 (E-cadherin) gene in
breast cancer patients from Kashmir.
AB - BACKGROUND: Aberrant promoter hypermethylation has been recognized in human
breast carcinogenesis as a frequent molecular alteration associated with the loss
of expression of a number of key regulatory genes and may serve as a biomarker.
The E-cadherin gene (CDH1), mapping at chromosome 16q22, is an intercellular
adhesion molecule in epithelial cells, which plays an important role in
establishing and maintaining intercellular connections. The aim of our study was
to assess the methylation pattern of CDH1 and to correlate it with the expression
of E-cadherin, clinicopathological parameters and hormone receptor status in
breast cancer patients of Kashmir. MATERIALS AND METHODS: Methylation specific
PCR (MSP) was used to determine the methylation status of CDH1 in 128 invasive
ductal carcinomas (IDCs) paired with the corresponding normal tissue samples.
Immunohistochemistry was used to study the expression of E-cadherin, ER and PR.
RESULTS: CDH1 hypermethylation was detected in 57.8% of cases and 14.8% of normal
adjacent controls. Reduced levels of E-cadherin protein were observed in 71.9% of
our samples. Loss of E-cadherin expression was significantly associated with the
CDH1 promoter region methylation (p<0.05, OR=3.48, CI: 1.55-7.79).
Hypermethylation of CDH1 was significantly associated with age at diagnosis
(p=0.030), tumor size (p=0.008), tumor grade (p=0.024) and rate of node
positivity or metastasis (p=0.043). CONCLUSIONS: Our preliminary findings suggest
that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast
cancers associated with a decrease in E-cadherin expression. We found significant
differences in tumor-related CDH1 gene methylation patterns relevant to tumor
grade, tumor size, nodal involvement and age at diagnosis of breast tumors, which
could be extended in future to provide diagnostic and prognostic information.
PMID- 25124633
TI - Prevalence of abnormal anal cytology in HIV-infected women: a hospital-based
study.
AB - BACKGROUND: To study the prevalence of abnormal anal cytology by Papanicolaou
(Pap) technique in HIV- infected women who attended a HIV clinic at Prapokklao
Hospital, Chanthaburi, Thailand. MATERIALS AND METHODS: HIV-infected women who
attended a HIV clinic at Prapokklao Hospital from March 2013 to February 2014
were recruited for anal Pap smears. Participants who had abnormal results of
equally or over "abnormal squamous/glandular cells of undetermined significance"
(ASC-US) were classified as abnormal anal cytology. RESULTS: A total of 590 anal
Pap smears were performed at HIV clinic of Prapokklao Hospital during the study
period. There were only 13 patients who had abnormal Pap tests, which were: 11
ASC-US and 2 HSIL (high grade squamous intraepithelial lesion). The prevalence of
abnormal anal Pap smears in HIV-infected women who attended HIV clinic at
Prapokklao Hospital was 2.2 percent. Percentage of high risk HPV in patients who
had abnormal Pap test was 88.9 (8/9). CONCLUSIONS: The prevalence of abnormal
anal Papanicolaou smears in HIV-infected women who attended the HIV clinic at
Prapokklao hospital was quite low in comparison to the earlier literature.
PMID- 25124634
TI - Analysis of mammographic breast density in a group of screening chinese women and
breast cancer patients.
AB - BACKGROUND: A dense breast not only reduces the sensitivity of mammography but
also is a moderate independent risk factor for breast cancer. The percentage of
Western women with fat breast tissue is higher aged 40 years or older. To a
certain extent, mammography as a first choice of screening imaging method for
Western women of this group is reasonable. Hitherto, the frequency and age
distribution of mammographic breast density patterns among Chinese women had not
been characterized. The purpose of this study was to investigate the frequency
and age distribution of mammographic breast density patterns among a group of
Chinese screening women and breast cancer patients in order to provide useful
information for age-specific guidelines for breast cancer screening in Chinese
women. METHODS: A retrospective review of a total of 3,394 screening women
between August and December 2009 and 2,527 breast cancer patients between July
2011 and June 2012 was conducted. Descriptive analyses were used to examine the
association between age and breast density. The significance of differences of
breast density between the screening women and the breast cancer patients was
examined using nonparametric tests. RESULTS: There was a significant inverse
relationship between age and breast density overall (r=-0.37, p<0.01). Breast
density of the breast cancer patients in the subgroups of 40-49 years old was
greater compared with that of the screening women, the same in those aged 50-54
years and in those 55 years old or older, less than in the screening group.
CONCLUSIONS: With regard to the Chinese women younger than 55 years old, the
diagnostic efficiency of breast cancer screening imaging examinations may be
potentially improved by combining screening mammography with ultrasound.
PMID- 25124635
TI - Relationship between the SER treatment period and prognosis of patients with
small cell lung cancer.
AB - PURPOSE: To explore the relationship between SER (time between the start of any
treatment and the end of radiation therapy) and the survival of patients with
limited-stage small cell lung cancer. MATERIALS AND METHODS: Between 2008 and
2013, 135 cases of limited-stage small cell lung cancer (LS-SCLC) treated with
consecutively curative chemoradiotherapy were included in this retrospective
analysis. In terms of SER, patients were divided into early radiotherapy group
(SER<30 days, n=76) and late radiotherapy group (SER>=30 days, n=59) with a cut-
off of SER 30 days. Outcomes of the two groups were compared for overall
survival. RESULTS: For all analyzable patients, median follow-up time was 23.8
months and median overall survival time was 16.8 months. Although there was no
significant differences in distant metastasis free survival between the two
groups, patients in early radiotherapy group had a significantly better PFS
(p=0.003) and OS (p=0.000). CONCLUSIONS: A short SER may be a good prognostic
factor for LD-SCLC patients treated with concurrent chemoradiotherapy.
PMID- 25124636
TI - Mean platelet volume as a prognostic marker in metastatic colorectal cancer
patients treated with bevacizumab-combined chemotherapy.
AB - BACKGROUND: Recent studies have revealed a prognostic impact of the MPV (mean
platelet volume)/platelet count ratio in terms of survival in advanced non-small
cell lung cancer. However, there has been no direct analysis of the survival
impact of MPV in patients with mCRC. The aim of the study is to evaluate the
pretreatment MPV of patients with metastatic and non-metastatic colorectal cancer
(non-mCRC) and also the prognostic significance of pretreatment MPV to
progression in mCRC patients treated with bevacizumab-combined chemotherapy.
MATERIALS AND METHODS: Fifty-three metastatic and ninety-five non-metastatic
colorectal cancer patients were included into the study. Data on sex, age, lymph
node status, MPV, platelet and platecrit (PCT) levels were obtained
retrospectively from the patient medical records. RESULTS: The MPV was
significantly higher in the patients with mCRC compared to those with non-mCRC
(7.895+/-1.060 versus 7.322+/-1.136, p=0.013). The benefit of bevacizumab on PFS
was significantly greater among the patients with low MPV than those with high
MPV. The hazard ratio (HR) of disease progression was 0.41 (95%CI, 0.174-0.986;
p=0.04). In conclusion, despite the retrospective design and small sample size,
MPV can be considered a prognostic factor for mCRC patients treated with
bevacizumab-combined chemotherapy.
PMID- 25124638
TI - Dimethylnitrosamine-induced reduction in the level of poly-ADP-ribosylation of
histone proteins of blood lymphocytes--a sensitive and reliable biomarker for
early detection of cancer.
AB - Poly-ADP-ribosylation (PAR) is a post-translational modification of mainly
chromosomal proteins. It is known to be strongly involved in several molecular
events, including nucleosome-remodelling and carcinogenesis. In this
investigation, it was attempted to evaluate PAR level as a reliable biomarker for
early detection of cancer in blood lymphocyte histones. PAR of isolated histone
proteins was monitored in normal and dimethylnitrosamine (DMN)-exposed mice
tissues using a novel ELISA-based immuno-probe assay developed in our laboratory.
An inverse relationship was found between the level of PAR and period of DMN
exposure in various histone proteins of blood lymphocytes and spleen cells. With
the increase in the DMN exposure period, there was reduction in the PAR level of
individual histones in both cases. It was also observed that the decrease in the
level of PAR of histones resulted in progressive relaxation of genomic DNA,
perhaps triggering activation of genes that are involved in initiation of
transformation. The observed effect of carcinogen on the PAR of blood lymphocyte
histones provided us with a handy tool for monitoring biochemical or
physiological status of individuals exposed to carcinogens without obtaining
biopsies of cancerous tissues, which involves several medical and ethical issues.
Obtaining blood from any patient and separating blood lymphocytes are routine
medical practices involving virtually no medical intervention, post-procedure
medical care or trauma to a patient. Moreover, the immuno-probe assay is very
simple, sensitive, reliable and cost-effective. Therefore, combined with the ease
of preparation of blood lymphocytes and the simplicity of the technique, immuno
probe assay of PAR has the potential to be applied for mass screening of cancer.
It appears to be a promising step in the ultimate goal of making cancer detection
simple, sensitive and reliable in the near future.
PMID- 25124637
TI - Overexpression of HER-2/neu in patients with prostatic adenocarcinoma.
AB - BACKGROUND: Prostatic adenocarcinoma is one of the main causes of cancer death,
and its timely diagnosis and preventing its progression dramatically helps
improve life indexes. Given the high disease recurrence rate, today, research is
more inclined toward exploring causes of recurrence and development, and
innovation of modern treatment methods. Several studies have explored over
expression of human epidermal growth factor receptor 2 (HER-2/neu) in prostatic
cancer so far, with different results. Thus, it was decided to investigate HER
2/neu overexpression in patients with prostatic adenocarcinoma in Iran. MATERIALS
AND METHODS: A sample size of 40 patients with prostate cancer entered the study,
using a cross-sectional, non-randomized sampling method. Parameters studied
included patient age at surgery, Gleason score, serum prostatic specific antigen
(PSA) before surgery, and positive sample rate after immunohistochemical staining
to investigate HER-2/neu overexpression. RESULTS: In terms of HER-2/neu receptor
staining rate, of 40 slides, 16 (40%) scored 0, 13 (32.5%) 1+, 7 (17.5%) 2+, and
4 (10%) 3+. In total 27.5% of slides showed HER-2/neu overexpression. In terms of
age, an inverse correlation was found (-0.181), but without significance
(p=0.263). In terms of serum PSA, the correlation coefficient was 0.449
(p=0.004). With respect to Gleason score, the coefficient was 0.190 (p=0.240).
CONCLUSIONS: In this study, HER-2/neu overexpression occurred in 27.5% of
prostate cancer cases, which is a relatively high figure, compared to similar
studies elsewhere. While, we failed to reveal any relationship between HER-2/neu
expression status with progression and prognosis of disease, it was demonstrated
that the serum PSA level was significantly higher in cases with increased
receptor expression.
PMID- 25124639
TI - Downregulation of Cdk1 and cyclinB1 expression contributes to oridonin-induced
cell cycle arrest at G2/M phase and growth inhibition in SGC-7901 gastric cancer
cells.
AB - BACKGROUND: Oridonin isolated from Rabdosia rubescens, a plant used to treat
cancer in Chinese folk medicine, is one of the most important antitumor active
ingredients. Previous studies have shown that oridonin has anti- tumor activities
in vivo and in vitro, but little is known about cell cycle effects of oridonin in
gastric cancer. MATERIALS AND METHODS: MTT assay was adopted to detect the
proliferation inhibition of SGC-7901 cells, the cell cycle was assessed by flow
cytometry and protein expression by Western blotting. RESULTS: Oridonin could
inhibit SGC-7901 cell proliferation, the IC50 being 15.6 MUM, and blocked SGC
7901 cell cycling in the G2/M phase. The agent also decreased the protein
expression of cyclinB1 and CDK1. CONCLUSIONS: Oridonin may inhibit SGC-7901
growth and block the cells in the G2/M phase by decreasing Cdk1 and cyclinB1
proteins.
PMID- 25124640
TI - Baseline stimulated thyroglobulin level as a good predictor of successful
ablation after adjuvant radioiodine treatment for differentiated thyroid cancers.
AB - BACKGROUND: To determine the predictive value of the baseline stimulated
thyroglobulin (STg) level for ablation outcome in patients undergoing adjuvant
remnant radioiodine ablation (RRA) for differentiated thyroid carcinoma (DTC).
MATERIALS AND METHODS: This retrospective study accrued 64 patients (23 male and
41 female; mean age of 40+/-14 years) who had total thyroidectomy followed by RRA
for DTC from January 2012 till April 2014. Patients with positive anti-Tg
antibodies and distant metastasis on post-ablative whole body iodine scans
(TWBIS) were excluded. Baseline STg was used to predict successful ablation
(follow-up STg<2 ng/ml, negative diagnostic WBIS and negative ultrasound neck) at
7-12 months follow-up. RESULTS: Overall, successful ablation was noted in 37
(58%) patients while ablation failed in 27 (42%). Using the ROC curve, a cut-off
level of baseline STg level of <=14.5 ng/ml was found to be most sensitive and
specific for predicting successful ablation. Successful ablation was thus noted
in 25/28 (89%) of patients with baseline STg<=14.5 ng/ml and 12/36 (33%) patients
with baseline STg>14.5 ng/ml ((p value<0.05). Age>40 years, female gender, PTS>2
cm, papillary histopathology, positive cervical nodes and positive TWBIS were
significant predictors of ablation failure. CONCLUSIONS: We conclude that in
patients with total thyroidectomy followed by I-131 ablation for DTC, the
baseline STg level is a good predictor of successful ablation based on a
stringent triple negative criteria (i.e. follow-up STg <2 ng/ ml, a negative
DWBIS and a negative US neck).
PMID- 25124641
TI - Albumin-globulin ratio for prediction of long-term mortality in lung
adenocarcinoma patients.
AB - BACKGROUND: Prior studies showed a relationship between serum albumin and the
albumin to globulin ratio with different types of cancer. We aimed to evaluate
the predictive value of the albumin-globulin ratio (AGR) for survival of patients
with lung adenocarcinoma. MATERIALS AND METHODS: This retrospective study
included 240 lung adenocarcinoma patients. Biochemical parameters before
chemotherapy were collected and survival status was obtained from the hospital
registry. The AGR was calculated using the equation AGR=albumin/ (total protein
albumin) and ranked from lowest to highest, the total number of patients being
divided into three equal tertiles according to the AGR values. Furthermore, AGR
was divided into two groups (low and high tertiles) for ROC curve analysis. Cox
model analysis was used to evaluate the prognostic value of AGR and AGR tertiles.
RESULTS: The mean survival time for each tertile was: for the 1st 9.8 months
(95%CI:7.765-11.848), 2nd 15.4 months (95%CI:12.685-18.186), and 3rd 19.9 months
(95%CI:16.495-23.455) (p<0.001). Kaplan-Meier curves showed significantly higher
survival rates with the third and high tertiles of AGR in comparison with the
first and low tertiles, respectively. At multivariate analysis low levels of
albumin and AGR, low tertile of AGR and high performance status remained an
independent predictors of mortality. CONCLUSIONS: Low AGR was a significant
predictor of long-term mortality in patients with lung adenocarcinoma. Serum
albumin measurement and calculation of AGR are easily accessible and cheap to use
for predicting mortality in patients with lung adenocarcinoma.
PMID- 25124643
TI - Stathmin 1, a therapeutic target in esophageal carcinoma?
PMID- 25124642
TI - Five-year survival and median survival time of nasopharyngeal carcinoma in
Hospital Universiti Sains Malaysia.
AB - BACKGROUND: Nasopharyngeal carcinoma (NPC) is the fourth most common cancer in
Malaysia. The objective of this study was to determine the five-year survival
rate and median survival time of NPC patients in Hospital Universiti Sains
Malaysia (USM). METHODS: One hundred and thirty four NPC cases confirmed by
histopathology in Hospital USM between 1st January 1998 and 31st December 2007
that fulfilled the inclusion and exclusion criteria were retrospectively
reviewed. Survival time of NPC patients were estimated by Kaplan-Meier survival
analysis. Log-rank tests were performed to compare survival of cases among
presenting symptoms, WHO type, TNM classification and treatment modalities.
RESULTS: The overall five-year survival rate of NPC patients was 38.0% (95%
confidence interval (CI): 29.1, 46.9). The overall median survival time of NPC
patients was 31.30 months (95%CI: 23.76, 38.84). The significant factors that
altered the survival rate and time were age (p=0.041), cranial nerve involvement
(p=0.012), stage (p=0.002), metastases (p=0.008) and treatment (p<0.001).
CONCLUSION: The median survival of NPC patients is significantly longer for
age<=50 years, no cranial nerve involvement, and early stage and is dependent on
treatment modalities.
PMID- 25124644
TI - Fast cell cycle analysis for intraoperative characterization of brain tumor
margins and malignancy.
AB - Flow cytometry, although indispensable for the characterization of hematologic
malignancies, has not been extensively evaluated in solid tumors. To date
intraoperative pathology evaluation of frozen sections of tissue obtained during
surgery is the gold standard for intraoperative diagnosis. We investigated the
value of a modified rapid protocol for cell cycle analysis for the intraoperative
characterization of intracranial lesions and their surgical margins. We
investigated patients who underwent surgery for an intracranial lesion suspicious
for a tumor. DNA analysis and frozen sections were performed on tumor samples
that were taken during surgery. Thirty-one patients met the inclusion criteria
for the study. There was a significant difference in G0/G1 phase between high
grade and low-grade tumors. Receiver operating characteristic (ROC) analysis
provided 75% of G0/G1 fraction as the optimal cutoff value thresholding the
discrimination between low and high-grade tumors. There was a significant
difference in S-phase and mitoses fraction between high-grade and low-grade
tumors. ROC analysis indicated 6% of S-phase and 9.7% of mitoses as the optimal
cutoff values thresholding the discrimination between these two groups. In the
glioblastoma patients, we also analyzed the perilesional tissue and found
significant differences between tumor mass and margins regarding the G0/G1 phase,
the S-phase and mitoses fraction. In conclusion rapid cell cycle analysis is a
method capable of differentiating low from high-grade tumors and delineating
tumor margins in gliomas. Thus, the role of cell cycle analysis in brain tumors
warrants further investigation.
PMID- 25124645
TI - Coccidioides parenchymal cerebral abscess in the setting of lymphoma.
AB - Coccidioides immitis is a dimorphic fungus endemic to southwestern United States
of America. When symptomatic, infection usually results in a subacute respiratory
infection. Disseminated coccidioidomycosis occurs in less than 1% of all cases.
We report a patient with follicular lymphoma and recent travel to Arizona, who
underwent resection of a cerebral Coccidioides abscess. Serology testing was
negative. This case highlights the importance of clinical suspicion in patients
with neurologic symptoms and travel to an endemic location.
PMID- 25124646
TI - Obsessive compulsive disorder due to a cavernous malformation hemorrhage in the
dominant caudate head.
AB - Structural lesions of the basal ganglia may lead to obsessive compulsive disorder
(OCD). We report a 31-year-old woman who developed OCD after a previously
asymptomatic left caudate intracerebral cavernous malformation (ICM) hemorrhaged.
Her neurologic examination was normal. Her OCD required hospitalization and
improved with medication and therapy. The pathophysiology of this psychiatric
disorder probably reflects a frontal cortex deafferentation mechanism. In
patients with known ICM, any abrupt change in neurologic or psychiatric symptoms
should prompt repeat imaging to assess for hemorrhage.
PMID- 25124647
TI - Weight and fat distribution in patients taking valproate: a valproate-discordant
gender-matched twin and sibling pair study.
AB - OBJECTIVES: Chronic treatment with valproate (VPA) is commonly associated with
weight gain, which potentially has important health implications, in particular
increased central fat distribution. We utilized a VPA-discordant same-sex, twin
and matched sibling pair study design to primarily examine for differences in fat
distribution between patients with epilepsy treated with VPA compared to their
matched twin or sibling control. Weight, blood pressure, and leptin levels were
assessed. METHODS: Height, weight, waist and hip measurements, exercise, blood
pressure (BP), and serum leptin levels were measured. Body composition was
measured using dual-energy x-ray absorptiometry (DXA). Abdominal fat was
expressed as a percentage of the abdominal region (AFat%); and of whole body fat
(WBF); (AFat%WBF). Mean within-pair differences were assessed (VPA-user and
nonuser). Restricted maximum likelihood (REML) linear mixed model analysis was
fitted to examine associations of anthropometrics, zygosity, gender, menopausal
status, VPA dose and duration, with weight and AFat%. RESULTS: We studied 19
pairs of VPA-discordant, gender-matched (five male, 14 female) twins and
siblings. Mean (standard deviation, SD) duration of therapy for VPA users was
11.0 (7.4) years. There were no statistically significant within-pair differences
in age, height, weight, body mass index (BMI), BP, leptin level, WBF, AFat%, or
AFat%WBF. For pairs in which VPA-user was treated for >11 years there were
statistically significant mean within-pair differences in AFat%, (+7.1%, p =
0.03, n = 10 pairs), mean BP (+11.0 mm Hg, p = 0.006, n = 8 pairs); but not in
AFat%WBF. VPA duration was positively associated with weight (estimate +0.98
kg/per year of VPA, p = 0.03); VPA treatment duration and dose were not
significantly associated with AFat%. SIGNIFICANCE: This study demonstrated a
relationship between long-term VPA use and abdominal adiposity (AFat%), which
could have significant health implications. We recommend ongoing monitoring of
weight, BMI, and blood pressure for patients taking VPA.
PMID- 25124648
TI - Prevalence and predictors of genito-pelvic pain in pregnancy and postpartum: the
prospective impact of fear avoidance.
AB - INTRODUCTION: There is limited knowledge regarding the symptom profile of genito
pelvic pain in pregnancy and postpartum, and potential psychosocial predictors of
this pain. Prior studies have reported a positive association between
prepregnancy pain and postpartum genito-pelvic pain. Greater fear avoidance has
been associated with increased genital pain intensity in women, unrelated to
childbirth. This relationship has not been examined prospectively in a postpartum
population. AIMS: The study aims were to examine the symptom profile of genito
pelvic pain during pregnancy and at 3 months postpartum, and the impact of
prepregnancy nongenito-pelvic pain and fear avoidance in pregnancy on genito
pelvic pain at 3 months postpartum. METHODS: First-time expectant mothers (N =
150) completed measures of fear avoidance (pain-related anxiety, catastrophizing,
hypervigilance to pain), prepregnancy nongenito-pelvic pain, childbirth-related
risk factors (e.g., episiotomy), and breastfeeding. MAIN OUTCOME MEASURES: Those
reporting genito-pelvic pain in pregnancy and/or at 3 months postpartum answered
questions about the onset (prepregnancy, during pregnancy, postpartum) and
location (genital, pelvic, or both) of the pain and rated the intensity and
unpleasantness of the pain on numerical rating scales. RESULTS: Of 150 women, 49%
reported genito-pelvic pain in pregnancy. The pain resolved for 59% of women,
persisted for 41%, and 7% of women reported a new onset of genito-pelvic pain
after childbirth. Prepregnancy nongenito-pelvic pain was associated with an
increased likelihood of postpartum onset of genito-pelvic pain. Greater pain
related anxiety was associated with greater average genito-pelvic pain intensity
at 3 months postpartum. CONCLUSIONS: Results suggest that about half of women may
develop genito-pelvic pain during pregnancy, which will persist for about a
third, and a subset will develop this pain after childbirth. Prior recurrent
nongenito-pelvic pain may enhance the risk of developing genito-pelvic pain
postpartum, while greater pain-related anxiety in pregnancy may increase the risk
for greater intensity of postpartum genito-pelvic pain.
PMID- 25124649
TI - EEG feature pre-processing for neonatal epileptic seizure detection.
AB - Aim of our project is to further optimize neonatal seizure detection using
support vector machine (SVM). First, a Kalman filter (KF) was used to filter both
feature and classifier output time series in order to increase temporal
precision. Second, EEG baseline feature correction (FBC) was introduced to reduce
inter patient variability in feature distributions. The performance of the
detection methods is evaluated on 54 multi channel routine EEG recordings from 39
both term and pre-term newborns. The area under the receiver operating
characteristics curve (AUC) as well as sensitivity and specificity are used to
evaluate the performance of the classification method. SVM without KF and FBC
achieves an AUC of 0.767 (sensitivity 0.679, specificity 0.707). The highest AUC
of 0.902 (sensitivity 0.801, specificity 0.831) is achieved on baseline corrected
features with a Kalman smoother used for training data pre-processing and a KF
used to filter the classifier output. Both FBC and KF significantly improve
neonatal epileptic seizure detection. This paper introduces significant
improvements for the state of the art SVM based neonatal epileptic seizure
detection.
PMID- 25124650
TI - An experimental and numerical investigation of head dynamics due to stick impacts
in girls' lacrosse.
AB - A method of investigating head acceleration and intracranial dynamics from stick
impacts in girls' and women's lacrosse was developed using headform impact
experiments and a finite element head model. Assessing the likelihood of head
injury due to stick-head impacts is of interest in girls' and women's lacrosse
due to the current lack of head protection during play. Experimental and
simulation data were compared to characterize the head acceleration caused by
stick-head impacts. Validation against cadaver head impact experiments ensures
that the finite element model, with its relatively simple material properties,
can provide means to develop a better understanding of the intracranial dynamics
during lacrosse stick impacts. Our numerical results showed the peak acceleration
at the center of gravity increased linearly with impact force, and was generally
in agreement with the experimental data. von Mises stresses and peak principal
strains, two common literature injury indicators, were examined within the finite
element model, and peak values were below the previously reported thresholds for
mild traumatic brain injury. By reconstructing typical in-game, unprotected stick
head impacts, this investigation lays the foundation for a quantitative
methodology of injury prediction in girls' and womens' lacrosse.
PMID- 25124651
TI - Individual and community-level determinants of mental and physical health after
the deepwater horizon oil spill: findings from the gulf States population survey.
AB - The 2010 Deepwater Horizon oil spill had enormous consequences on the
environment. Prevalence of mental and physical health conditions among Gulf
residents after the disaster, however, are still being assessed. The Gulf State
Population Survey (GSPS) was a representative survey of 38,361 residents in four
Gulf States and was conducted from December 2010 to December 2011. Analysis of
the GSPS data showed that differences in individual characteristics and direct or
indirect exposure to the disaster drove the individual-level variation in health
outcomes (mental distress, physical distress, and depression). Direct exposure to
the disaster itself was the most important determinant of health after this
event. Selected county-level characteristics were not found to be significantly
associated with any of our health indicators of interest. This study suggests
that in the context of an overwhelming event, persons who are most directly
affected through direct exposure should be the primary focus of any public health
intervention effort.
PMID- 25124653
TI - Oncometabolites-driven tumorigenesis: From genetics to targeted therapy.
AB - Although the alteration of cellular metabolism in cancer was reported by Warburg
in the early 1930s, a regain of interest in cancer metabolism has more recently
followed the discovery of germline or somatic mutations in genes coding for
metabolic enzymes (succinate dehydrogenase, fumarate hydratase and isocitrate
dehydrogenase) that are associated with tumor susceptibility. Mutations in these
genes are found in numerous tumor types including paragangliomas, kidney cancers,
leiomyomas, glioblastomas and acute myeloid leukemia. They lead to the
accumulation of so-called oncometabolites that behave as competitors of 2
oxoglutarate-dependent dioxygenases, involved in a broad spectrum of pathways
such as hypoxic response and epigenetic reprogramming. Here, we review the
diverse pathways affected by oncometabolites, their potential role in cancer
formation, maintenance, metastasis and sensitivity to chemotherapies, as well as
emerging new therapeutic strategies.
PMID- 25124654
TI - Reversal of toxic manifestations of chlorpromazine.
PMID- 25124652
TI - Differential Effects of Mental Health Problems Among Truant Youths.
AB - Research indicates at-risk youth are more likely to experience emotional and
psychological problems. Young people who are often truant from school represent a
group of at-risk youth, but one for which mental health issues are understudied.
This study examined heterogeneity of mental health problems among a sample of 300
truant adolescents using latent class analysis (LCA). LCA indicated the sample of
truants was best represented by four latent subgroups of youth with low mental
health problems; high depression, low mania; high mania, low depression; and high
depression and mania. These subgroups were examined in relation to
sociodemographic and psychosocial measures at baseline and after truancy
offenses. Results indicated general and unique differences in these covariates
across the four latent classes. Service and practice implications of better
understanding mental health issues of truant youth are discussed.
PMID- 25124655
TI - Sensory differences between beet and cane sugar sources.
AB - Research concerning the sensory properties of beet and cane sugars is lacking in
the scientific literature. Therefore, the objectives of this research were to
determine whether a sensory difference was perceivable between beet and cane
sugar sources in regard to their (1) aroma-only, (2) aroma and taste without nose
clips, and (3) taste-only with nose clips, and to characterize the difference
between the sugar sources using descriptive analysis. One hundred panelists
evaluated sugar samples using a tetrad test. A significant difference (P < 0.05)
was identified between beet and cane sugar sources when evaluated by aroma-only
and taste and aroma without nose clips. However, there was no difference when
tasted with nose clips. To characterize the observed differences, ten trained
panelists identified and quantified key sensory attributes of beet and cane
sugars using descriptive analysis. Analysis of variance indicated significant
differences (P < 0.05) between sugar samples for 8 of the 10 attributes
including: off-dairy, oxidized, earthy, and barnyard aroma, fruity and burnt
sugar aroma-by-mouth, sweet aftertaste, and burnt sugar aftertaste. The sensory
profile of beet sugar was characterized by off-dairy, oxidized, earthy, and
barnyard aromas and by a burnt sugar aroma-by-mouth and aftertaste, whereas cane
sugar was characterized by a fruity aroma-by-mouth and sweet aftertaste. This
study shows that beet and cane sugar sources can be differentiated by their aroma
and provides a sensory profile characterizing the differences. As sugar is used
extensively as a food ingredient, sensory differences between beet and cane sugar
sources once incorporated into different product matrices should be studied as a
next step.
PMID- 25124656
TI - Identification of Malassezia species in the facial lesions of Chinese seborrhoeic
dermatitis patients based on DNA sequencing.
AB - The genus Malassezia is important in the aetiology of facial seborrhoeic
dermatitis (FSD), which is the most common clinical type. The purpose of this
study was to analyse the distribution of Malassezia species in the facial lesions
of Chinese seborrhoeic dermatitis (SD) patients and healthy individuals. Sixty
four isolates of Malassezia were isolated from FSD patients and 60 isolates from
healthy individuals. Sequence analysis of the internal transcribed spacer (ITS)
region was used to identify the isolates. The most frequently identified
Malassezia species associated with FSD was M. furfur (76.56%), followed by M.
sympodialis (12.50%) and M. japonica (9.38%). The most frequently isolated
species in healthy individuals were M. furfur (61.67%), followed by M.
sympodialis (25.00%), M. japonica (6.67%), M. globosa (3.33%), and M. obtusa
(3.33%). Overall, our study revealed that while M. furfur is the predominant
Malassezia species in Chinese SD patients, there is no significant difference in
the distribution of Malassezia species between Chinese SD patients and healthy
individuals.
PMID- 25124658
TI - Duelling letters: which one would you sign?
PMID- 25124657
TI - New less invasive ventricular reconstruction technique in the treatment of
ischemic heart failure.
AB - Ischemic cardiomyopathy is the leading cause of heart failure. In patients with
left ventricular (LV) dilatation, low ejection fraction, and transmural scar in
an anteroseptal distribution, surgical ventricular reconstruction (SVR) is a
treatment option. We describe our first experience with the Less Invasive
Ventricular Enhancement (LIVE) technique using the ReviventTM system (Bioventrix
Inc., San Ramon, CA), in the treatment of a large anteroapical aneurysm.
PMID- 25124661
TI - Epigenetic epidemiology of cancer.
AB - Epigenetic epidemiology includes the study of variation in epigenetic traits and
the risk of disease in populations. Its application to the field of cancer has
provided insight into how lifestyle and environmental factors influence the
epigenome and how epigenetic events may be involved in carcinogenesis.
Furthermore, it has the potential to bring benefit to patients through the
identification of diagnostic markers that enable the early detection of disease
and prognostic markers that can inform upon appropriate treatment strategies.
However, there are a number of challenges associated with the conduct of such
studies, and with the identification of biomarkers that can be applied to the
clinical setting. In this review, we delineate the challenges faced in the design
of epigenetic epidemiology studies in cancer, including the suitability of blood
as a surrogate tissue and the capture of genome-wide DNA methylation. We describe
how epigenetic epidemiology has brought insight into risk factors associated with
lung, breast, colorectal and bladder cancer and review relevant research. We
discuss recent findings on the identification of epigenetic diagnostic and
prognostic biomarkers for these cancers.
PMID- 25124662
TI - Over-expression of Oct4 and Sox2 transcription factors enhances differentiation
of human umbilical cord blood cells in vivo.
AB - Gene and cell-based therapies comprise innovative aspects of regenerative
medicine. Even though stem cells represent a highly potential therapeutic
strategy, their wide-spread exploitation is marred by ethical concerns, potential
for malignant transformation and a plethora of other technical issues, largely
restricting their use to experimental studies. Utilizing genetically modified
human umbilical cord blood mono-nuclear cells (hUCB-MCs), this communication
reports enhanced differentiation of transplants in a mouse model of amyotrophic
lateral sclerosis (ALS). Over-expressing Oct4 and Sox2 induced production of
neural marker PGP9.5, as well as transformation of hUCB-MCs into micro-glial and
endothelial lines in ALS spinal cords. In addition to producing new nerve cells,
providing degenerated areas with trophic factors and neo-vascularisation might
prevent and even reverse progressive loss of moto-neurons and skeletal muscle
paralysis.
PMID- 25124664
TI - Epistasis effects of COMT and MTHFR on inter-individual differences in mental
health: under the inverted U-shaped prefrontal dopamine model.
AB - Higher cognitive performance, maintenance of mental health and psychological well
being require adequate prefrontal cortex (PFC) function. "Inverted U-shaped"
dopamine model indicates optimal PFC dopamine level is important to attain its
function while high or low levels have adverse effects. Catechol-O
methyltransferase (COMT) and methylenetetrahydrofolate reductase (MTHFR) may be
involved in this complex non-linear PFC dopamine regulation. We addressed whether
genetic variation reflecting COMT and MTHFR activities can explain the inter
individual mental health differences in healthy Japanese men (n=188). The mental
health was measured by Mental Health Inventory (MHI)-5 score. The rs4633-rs4818
rs4680 haplotypes were used to represent the multilevel COMT activities, while
for MTHFR, the functional single polymorphism, rs1801133 (C677T), was used. We
examined the effectiveness of haplotype-based association analysis of COMT on
mental health together with studying its interaction with MTHFR-C677T. As a
result, the relation between activity-ranked COMT genotype and MHI-5 score showed
a tendency to fit into an "inverted U-shaped" quadratic curve (P=0.054). This
curvilinear correlation was significant in the subjects with MTHFR-CC (P<0.001),
but not with MTHFR T-allele carriers (P=0.793). Our pilot study implies a
potential influence of COMT and MTHFR genotypic combination on normal variation
of mental health.
PMID- 25124665
TI - Nascent histamine induces alpha-synuclein and caspase-3 on human cells.
AB - Histamine (Hia) is the most multifunctional biogenic amine. It is synthetized by
histidine decarboxylase (HDC) in a reduced set of mammalian cell types. Mast
cells and histaminergic neurons store Hia in specialized organelles until the
amine is extruded by exocytosis; however, other immune and cancer cells are able
to produce but not store Hia. The intracellular effects of Hia are still not well
characterized, in spite of its physiopathological relevance. Multiple functional
relationships exist among Hia metabolism/signaling elements and those of other
biogenic amines, including growth-related polyamines. Previously, we obtained the
first insights for an inhibitory effect of newly synthetized Hia on both growth
related polyamine biosynthesis and cell cycle progression of non-fully
differentiated mammalian cells. In this work, we describe progress in this line.
HEK293 cells were transfected to express active and inactive versions of GFP
human HDC fusion proteins and, after cell sorting by flow cytometry, the relative
expression of a large number of proteins associated with cell signaling were
measured using an antibody microarray. Experimental results were analyzed in
terms of protein-protein and functional interaction networks. Expression of
active HDC induced a cell cycle arrest through the alteration of the levels of
several proteins such as cyclin D1, cdk6, cdk7 and cyclin A. Regulation of alpha
synuclein and caspase-3 was also observed. The analyses provide new clues on the
molecular mechanisms underlying the regulatory effects of intracellular newly
synthetized Hia on cell proliferation/survival, cell trafficking and protein
turnover. This information is especially interesting for emergent and orphan
immune and neuroinflammatory diseases.
PMID- 25124663
TI - Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions
between tumor cells and stromal fibroblasts through IL-1alpha in ameloblastoma.
AB - Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which
invades bone and reoccurs locally. This tumor is treated by wide surgical
excision and causes various problems, including changes in facial countenance and
mastication disorders. Ameloblastomas have abundant tumor stroma, including
fibroblasts and immune cells. Although cell-to-cell interactions are considered
to be involved in the pathogenesis of many diseases, intercellular communications
in ameloblastoma have not been fully investigated. In this study, we examined
interactions between tumor cells and stromal fibroblasts via soluble factors in
ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma
cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts
from human ameloblastoma tissues, and analyzed the effect of ameloblastoma
associated cell-to-cell communications on gene expression, cytokine secretion,
cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher
levels of interleukin (IL)-1alpha than HFF-2 fibroblasts. Treatment with
conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and
secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast
cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8
in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1alpha
antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3
ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8
dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts
behave interactively via these cytokines to create a microenvironment that leads
to the extension of ameloblastomas.
PMID- 25124666
TI - Expression and localization of aquaporin-4 in sensory ganglia.
AB - Aquaporin-4 (AQP4) is a water channel protein that is predominantly expressed in
astrocytes in the CNS. The rapid water flux through AQP4 may contribute to
electrolyte/water homeostasis and may support neuronal activities in the CNS. On
the other hand, little is known about the expression of AQP4 in the peripheral
nervous system (PNS). Using AQP4(-/-) mice as a negative control, we demonstrated
that AQP4 is also expressed in sensory ganglia, such as trigeminal ganglia and
dorsal root ganglia in the PNS. Immunohistochemistry revealed that AQP4 is
exclusively localized to satellite glial cells (SGCs) surrounding the cell bodies
of the primary afferent sensory neurons in the sensory ganglia. Biochemical
analyses revealed that the expression levels of AQP4 in sensory ganglia were
considerably lower than those in astrocytes in the CNS. Consistently, behavioral
analyses did not show any significant difference in terms of mechanical and cold
sensitivity between wild type and AQP4(-/-) mice. Overall, although the
pathophysiological relevance of AQP4 in somatosensory perception remains unclear,
our findings provide new insight into the involvement of water homeostasis in the
peripheral sensory system.
PMID- 25124667
TI - Human decidual stromal cells secrete soluble pro-apoptotic factors during
decidualization in a cAMP-dependent manner.
AB - STUDY QUESTION: Is there a relationship between decidualization and apoptosis of
decidual stromal cells (DSC)? SUMMARY ANSWER: Decidualization triggers the
secretion of soluble factors that induce apoptosis in DSC. WHAT IS KNOWN ALREADY:
The differentiation and apoptosis of DSC during decidualization of the receptive
decidua are crucial processes for the controlled invasion of trophoblasts in
normal pregnancy. Most DSC regress in a time-dependent manner, and their removal
is important to provide space for the embryo to grow. However, the mechanism that
controls DSC death is poorly understood. STUDY DESIGN, SIZE, DURATION: The
apoptotic response of DSC was analyzed after exposure to different exogenous
agents and during decidualization. The apoptotic potential of decidualized DSC
supernatants and prolactin (PRL) was also evaluated. PARTICIPANTS/MATERIALS,
SETTING, METHODS: DSC lines were established from samples of decidua from first
trimester pregnancies. Apoptosis was assayed by flow cytometry. PRL production,
as a marker of decidualization, was determined by enzyme-linked immunosorbent
assay. MAIN RESULTS AND THE ROLE OF CHANCE: DSCs were resistant to a variety of
apoptosis-inducing substances. Nevertheless, DSC underwent apoptosis during
decidualization in culture, with cAMP being essential for both apoptosis and
differentiation. In addition, culture supernatants from decidualized DSC induced
apoptosis in undifferentiated DSC, although paradoxically these supernatants
decreased the spontaneous apoptosis of decidual lymphocytes. Exogenously added
PRL did not induce apoptosis in DSC and an antibody that neutralized the PRL
receptor did not decrease the apoptosis induced by supernatants. LIMITATIONS,
REASONS FOR CAUTIONS: Further studies are needed to examine the involvement of
other soluble factors secreted by decidualized DSC in the induction of apoptosis.
WIDER IMPLICATIONS OF THE FINDINGS: The present results indicate that apoptosis
of DSC occurs in parallel to differentiation, in response to decidualization
signals, with soluble factors secreted by decidualized DSC being responsible for
triggering cell death. These studies are relevant in the understanding of how the
regression of decidua, a crucial process for successful pregnancy, takes place.
STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Consejeria de
Economia, Innovacion y Ciencia, Junta de Andalucia (Grant CTS-6183, Proyectos de
Investigacion de Excelencia 2010 to C.R.-R.) and the Instituto de Salud Carlos
III, Ministerio de Economia y Competitividad, Spain (Grants PS09/00339 and
PI12/01085 to E.G.O.). E.L.-D. was supported by fellowships from the Ministerio
de Educacion y Ciencia, Spain and the University of Granada. The authors have no
conflict of interest.
PMID- 25124669
TI - Endometrial signals improve embryo outcome: functional role of vascular
endothelial growth factor isoforms on embryo development and implantation in
mice.
AB - STUDY QUESTION: Does vascular endothelial growth factor (VEGF) have important
roles during early embryo development and implantation? SUMMARY ANSWER: VEGF
plays key roles during mouse preimplantation embryo development, with beneficial
effects on time to cavitation, blastocyst cell number and outgrowth, as well as
implantation rate and fetal limb development. WHAT IS KNOWN ALREADY: Embryo
implantation requires synchronized dialog between maternal cells and those of the
conceptus. Following ovulation, secretions from endometrial glands increase and
accumulate in the uterine lumen. These secretions contain important mediators
that support the conceptus during the peri-implantation phase. Previously, we
demonstrated a significant reduction of VEGFA in the uterine cavity of women with
unexplained infertility. Functional studies demonstrated that VEGF significantly
enhanced endometrial epithelial cell adhesive properties and embryo outgrowth.
STUDY DESIGN, SIZE, DURATION: Human endometrial lavages (n = 6) were obtained
from women of proven fertility. Four-week old Swiss mice were superovulated and
mated with Swiss males to obtain embryos for treatment with VEGF in vitro.
Preimplantation embryo development was assessed prior to embryo transfer (n = 19
30/treatment group/output). Recipient F1 female mice (8-12 weeks of age) were
mated with vasectomized males to induce pseudopregnancy and embryos were
transferred. On Day 14.5 of pregnancy, uterine horns were collected for analysis
of implantation rates as well as placental and fetal development (n = 14
19/treatment). PARTICIPANTS/MATERIALS, SETTING, METHODS: Lavage fluid was
assessed by western immunoblot analysis to determine the VEGF isoforms present.
Mouse embryos were treated with either recombinant human (rh)VEGF, or VEGF
isoforms 121 and 165. Preimplantation embryo development was quantified using
time-lapse microscopy. Blastocysts were (i) stained for cell number, (ii)
transferred to wells coated with fibronectin to examine trophoblast outgrowth or
(iii) transferred to pseudo pregnant recipients to analyze implantation rates,
placental and fetal development. MAIN RESULTS AND THE ROLE OF CHANCE: Western
blot analysis revealed the presence of VEGF121 and 165 isoforms in human uterine
fluid. Time-lapse microscopy analysis revealed that VEGF (n = 22) and VEGF121 (n
= 23) treatment significantly reduced the preimplantation mouse embryo time to
cavitation (P < 0.05). VEGF and VEGF165 increased both blastocyst cell number
(VEGF n = 27; VEGF165 n = 24: P < 0.001) and outgrowth (n = 15/treatment: 66 h, P
< 0.001; 74, 90, 98 and 114 h, P < 0.01) on fibronectin compared with control.
Furthermore, rhVEGF improved implantation rates and enhanced fetal limb
development (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: Due to the nature of
this work, embryo development and implantation was only examined in the mouse.
WIDER IMPLICATIONS OF THE FINDINGS: The absence or reduction in levels of VEGF
during the preimplantation period likely affects key events during embryo
development, implantation and placentation. The potential for improvement of
clinical IVF outcomes by the addition of VEGF to human embryo culture media needs
further investigation. STUDY FUNDING/COMPETING INTERESTS: This study was
supported by a University of Melbourne Early Career Researcher Grant #601040, the
NHMRC (L.A.S., Program grant #494802; Fellowship #1002028; N.J.H., Fellowship #
628927; J.E.; project grant #1047756) and L.A.S., Monash IVF Research and
Education Foundation. N.K.B. was supported by an Australian Postgraduate Award.
Work at PHI-MIMR Institute was also supported by the Victorian Government's
Operational Infrastructure Support Program. There are no conflicts of interest to
declare.
PMID- 25124668
TI - Clinically relevant enhancement of human sperm motility using compounds with
reported phosphodiesterase inhibitor activity.
AB - STUDY QUESTION: Can we identify compound(s) with reported phosphodiesterase
inhibitor (PDEI) activity that could be added to human spermatozoa in vitro to
enhance their motility without compromising other sperm functions? SUMMARY
ANSWER: We have identified several compounds that produce robust and effective
stimulation of sperm motility and, importantly, have a positive response on
patient samples. WHAT IS KNOWN ALREADY: For >20 years, the use of non-selective
PDEIs, such as pentoxifylline, has been known to influence the motility of human
spermatozoa; however, conflicting results have been obtained. It is now clear
that human sperm express several different phosphodiesterases and these are
compartmentalized at different regions of the cells. By using type-specific
PDEIs, differential modulation of sperm motility may be achieved without
adversely affecting other functions such as the acrosome reaction (AR). STUDY
DESIGN, SIZE, DURATION: This was a basic medical research study examining sperm
samples from normozoospermic donors and subfertile patients attending the
Assisted Conception Unit (ACU), Ninewells Hospital Dundee for diagnostic semen
analysis, IVF and ICSI. Phase 1 screened 43 commercially available compounds with
reported PDEI activity to identify lead compounds that stimulate sperm motility.
Samples were exposed (20 min) to three concentrations (1, 10 and 100 uM) of
compound, and selected candidates (n = 6) progressed to Phase 2, which provided a
more comprehensive assessment using a battery of in vitro sperm function tests.
PARTICIPANTS/MATERIALS, SETTING, METHODS: All healthy donors and subfertile
patients were recruited at the Medical Research Institute, University of Dundee
and ACU, Ninewells Hospital Dundee (ethical approval 08/S1402/6). In Phase 1,
poor motility cells recovered from the 40% interface of the discontinuous density
gradient were used as surrogates for patient samples. Pooled samples from three
to four different donors were utilized in order to reduce variability and
increase the number of cells available for simultaneous examination of multiple
compounds. During Phase 2 testing, semen samples from 23 patients attending for
either routine diagnostic andrology assessment or IVF/ICSI were prepared and
exposed to selected compounds. Additionally, 48 aliquots of prepared samples,
surplus to clinical use, were examined from IVF (n = 32) and ICSI (n = 16)
patients to further determine the effects of selected compounds under clinical
conditions of treatment. Effects of compounds on sperm motility were assessed by
computer-assisted sperm analysis. A modified Kremer test using methyl cellulose
was used to assess sperm functional ability to penetrate into viscous media.
Sperm acrosome integrity and induction of apoptosis were assessed using the
acrosomal content marker PSA-FITC and annexin V kit, respectively. MAIN RESULTS
AND THE ROLE OF CHANCE: In Phase 1, six compounds were found to have a strong
effect on poor motility samples with a magnitude of response of >= 60% increase
in percentage total motility. Under capacitating and non-capacitating conditions,
these compounds significantly (P <= 0.05) increased the percentage of total and
progressive motility. Furthermore, these compounds enhanced penetration into a
cervical mucus substitute (P <= 0.05). Finally, the AR was not significantly
induced and these compounds did not significantly increase the externalization of
phosphatidylserine (P = 0.6, respectively). In general, the six compounds
maintained the stimulation of motility over long periods of time (180 min) and
their effects were still observed after their removal. In examinations of
clinical samples, there was a general observation of a more significant
stimulation of sperm motility in samples with lower baseline motility. In ICSI
samples, compounds #26, #37 and #38 were the most effective at significantly
increasing total motility (88, 81 and 79% of samples, respectively) and
progressive motility (94, 93 and 81% of samples, respectively). In conclusion,
using a two-phased drug discovery screening approach including the examination of
clinical samples, 3/43 compounds were identified as promising candidates for
further study. LIMITATIONS, REASONS FOR CAUTION: This is an in vitro study and
caution must be taken when extrapolating the results. Data for patients were from
one assessment and thus the robustness of responses needs to be established. The
n values for ICSI samples were relatively small. WIDER IMPLICATIONS OF THE
FINDINGS: We have systematically screened and identified several compounds that
have robust and effective stimulation (i.e. functional significance with
longevity and no toxicity) of total and progressive motility under clinical
conditions of treatment. These compounds could be clinical candidates with
possibilities in terms of assisted reproductive technology options for current or
future patients affected by asthenozoospermia or oligoasthenozoospermia. STUDY
FUNDING/COMPETING INTERESTS: This study was funded primarily by the MRC (DPFS)
but with additional funding from the Wellcome Trust, Tenovus (Scotland),
University of Dundee, NHS Tayside and Scottish Enterprise. The authors have no
competing interests. A patent (#WO2013054111A1) has been published containing
some of the information presented in this manuscript.
PMID- 25124671
TI - Effect of socioeconomic level on knowledge of stroke in the general population: A
social inequality gradient.
AB - OBJECTIVES: Socioeconomic status is a factor that influences health-related
behaviour in individuals as well as health conditions in entire populations. The
objective of the present study was to analyse the sociodemographic factors that
may influence knowledge of stroke. METHOD: Cross-sectional study. A
representative sample was selected by double randomisation. Face-to-face
interviews were carried out by previously trained medical students using a
structured questionnaire with open- and closed-ended questions. Adequate
knowledge was previously defined. The Mantel-Haenszel test and adjusted logistic
regression analysis were used to assess the association between knowledge of
stroke and the study variables. RESULTS: 2411 subjects were interviewed (59.9%
women; mean age 49.0 [SD 17.3] years) Seventy-three per cent were residents of
urban areas, 24.7% had a university education, and 15.2% had a low level of
schooling. Only 2.1% reported earning more than 40 000 euros/year, with 29.9%
earning less than 10 000. Nearly 74% reported having an excellent or good state
of health. The unemployment rate was 17.0%. Prevalence of "adequate knowledge"
was 39.7% (95% CI: 37.7%-41.6%). Trend analysis showed an association between
knowledge of stroke and income (z=10.14, P<0.0001); educational level (z=15.95,
P<0.0001); state of health (z=7.92, P<0.0001); and employment status (z=8.98,
P<0.0001). CONCLUSIONS: Educational level, income, employment status, and state
of health are independent factors for adequate knowledge of stroke. Public
awareness campaigns should present material using simple language and efforts
should be directed toward the most disadvantaged social strata in particular.
PMID- 25124670
TI - Use and acceptance of long lasting insecticidal net screens for dengue prevention
in Acapulco, Guerrero, Mexico.
AB - BACKGROUND: Dengue, recognized by the WHO as the most important mosquito-borne
viral disease in the world, is a growing problem. Currently, the only effective
way of preventing dengue is vector control. Standard methods have shown limited
effect, and there have been calls to develop new integrated vector management
approaches. One novel tool, protecting houses with long lasting insecticidal
screens on doors and windows, is being trialled in a cluster randomised
controlled trial by a joint UADY/WHO TDR/IDRC study in various districts of
Acapulco, Mexico, with exceptionally high levels of crime and insecurity.This
study investigated the community's perspectives of long lasting insecticidal
screens on doors and windows in homes and in schools, in order to ascertain their
acceptability, to identify challenges to further implementation and opportunities
for future improvements. METHODS: This was a sequential mixed-methods study. The
quantitative arm contained a satisfaction survey administered to 288 houses that
had received the intervention examining their perspectives of both the
intervention and dengue prevention in general. The qualitative arm consisted of
Focus Group Discussions (FGDs) with those who had accepted the intervention and
key informant interviews with: schoolteachers to discuss the use of the screens
in schools, program staff, and community members who had refused the
intervention. RESULTS: Overall satisfaction and acceptance of the screens was
very high, with only some operational and technical complaints relating to screen
fragility and the installation process. However, the wider social context of
urban violence and insecurity was a major barrier to screen acceptance. Lack of
information dissemination and community collaboration were identified as project
weaknesses. CONCLUSIONS: The screens are widely accepted by the population, but
the project implementation could be improved by reassuring the community of its
legitimacy in the context of insecurity. More community engagement and better
information sharing structures are needed.The screens could be a major new dengue
prevention tool suitable for widespread use, if further research supports their
entomological and epidemiological effectiveness and their acceptability in
different social and environmental contexts. Further research is needed looking
at the impact of insecurity of dengue prevention programmes.
PMID- 25124672
TI - Regarding emergency department consultations with neurologists. Author's reply.
PMID- 25124673
TI - Financial costs and personal consequences of research misconduct resulting in
retracted publications.
AB - The number of retracted scientific articles has been increasing. Most retractions
are associated with research misconduct, entailing financial costs to funding
sources and damage to the careers of those committing misconduct. We sought to
calculate the magnitude of these effects. Data relating to retracted manuscripts
and authors found by the Office of Research Integrity (ORI) to have committed
misconduct were reviewed from public databases. Attributable costs of retracted
manuscripts, and publication output and funding of researchers found to have
committed misconduct were determined. We found that papers retracted due to
misconduct accounted for approximately $58 million in direct funding by the NIH
between 1992 and 2012, less than 1% of the NIH budget over this period. Each of
these articles accounted for a mean of $392,582 in direct costs (SD $423,256).
Researchers experienced a median 91.8% decrease in publication output and large
declines in funding after censure by the ORI.
PMID- 25124675
TI - Systemic lupus erythematosus complicated with liver cirrhosis in a patient with
Papillon-Lefevre syndrome.
AB - We report the first case of a girl who presented with Papillon-Lefevre syndrome
(PLS) and subsequently developed systemic lupus erythematosus and liver
cirrhosis. This indicates that autoimmune diseases can be a complication in
patients with PLS. Cathepsin C gene mutations were not found in our patient or
her mother. Thus, other genetic factors may have been involved in this patient.
PMID- 25124674
TI - Considerations when investigating lncRNA function in vivo.
AB - Although a small number of the vast array of animal long non-coding RNAs
(lncRNAs) have known effects on cellular processes examined in vitro, the extent
of their contributions to normal cell processes throughout development,
differentiation and disease for the most part remains less clear. Phenotypes
arising from deletion of an entire genomic locus cannot be unequivocally
attributed either to the loss of the lncRNA per se or to the associated loss of
other overlapping DNA regulatory elements. The distinction between cis- or trans
effects is also often problematic. We discuss the advantages and challenges
associated with the current techniques for studying the in vivo function of
lncRNAs in the light of different models of lncRNA molecular mechanism, and
reflect on the design of experiments to mutate lncRNA loci. These considerations
should assist in the further investigation of these transcriptional products of
the genome.
PMID- 25124677
TI - Urine beta2-microglobulin is associated with clinical disease activity and renal
involvement in female patients with systemic lupus erythematosus.
AB - OBJECTIVE: We investigated the association of serum and urine beta2-microglobulin
(beta2MG) with renal involvement and clinical disease activity in systemic lupus
erythematosus (SLE). METHODS: Sixty-four female patients with SLE were enrolled.
We assessed SLE disease activity (SLEDAI)-2K and measured serum and urine beta2MG
levels, as well as complement (C3 and C4) and anti-dsDNA levels. According to the
SLEDAI scores, two groups were categorized: low (0-5 of SLEDAI) and high (6-19 of
SLEDAI) disease activity groups. The presence of renal involvement was determined
by renal SLEDAI score. Statistical analysis was performed using Spearman's
correlation analysis, Mann-Whitney U test, multivariate regression analysis, and
logistic regression analysis. RESULTS: Urine beta2MG levels were significantly
different between low and high SLEDAI groups (p = 0.001), but not for serum
beta2MG levels (p = 0.579). Patients with renal involvement showed higher urine
beta2MG levels compared to those without renal involvement (p < 0.001), but again
there was not a difference in serum beta2MG levels (p = 0.228). Urine beta2MG was
closely associated with SLEDAI (r = 0.363, p = 0.003), renal SLEDAI (r = 0.479, p
< 0.001), urine protein/Cr (r = 0.416, p = 0.001), and ESR (r = 0.347, p =
0.006), but not serum beta2MG (r = 0.245, p = 0.051). Urine beta2MG level was
identified as a surrogate for renal involvement (p = 0.009, OR = 1.017, 95% CI
1.004-1.030) and overall disease activity (p = 0.009, OR = 1.020, 95% CI 1.005
1.036). CONCLUSIONS: We demonstrated that urine beta2MG levels are associated
with renal involvement and overall clinical disease activity in SLE.
PMID- 25124678
TI - Elucidation of epithelial-mesenchymal transition-related pathways in a triple
negative breast cancer cell line model by multi-omics interactome analysis.
AB - In life sciences, and particularly biomedical research, linking aberrant pathways
exhibiting phenotype-specific alterations to the underlying physical condition or
disease is an ongoing challenge. Computationally, a key approach for pathway
identification is data enrichment, combined with generation of biological
networks. This allows identification of intrinsic patterns in the data and their
linkage to a specific context such as cellular compartments, diseases or
functions. Identification of aberrant pathways by traditional approaches is often
limited to biological networks based on either gene expression, protein
expression or post-translational modifications. To overcome single omics
analysis, we developed a set of computational methods that allow a combined
analysis of data collections from multiple omics fields utilizing hybrid
interactome networks. We apply these methods to data obtained from a triple
negative breast cancer cell line model, combining data sets of gene and protein
expression as well as protein phosphorylation. We focus on alterations associated
with the phenotypical differences arising from epithelial-mesenchymal transition
in two breast cancer cell lines exhibiting epithelial-like and mesenchymal-like
morphology, respectively. Here we identified altered protein signaling activity
in a complex biologically relevant network, related to focal adhesion and
migration of breast cancer cells. We found dysregulated functional network
modules revealing altered phosphorylation-dependent activity in concordance with
the phenotypic traits and migrating potential of the tested model. In addition,
we identified Ser267 on zyxin, a protein coupled to actin filament
polymerization, as a potential in vivo phosphorylation target of cyclin-dependent
kinase 1.
PMID- 25124679
TI - Distribution and accumulation of hexachlorobutadiene in soils and terrestrial
organisms from an agricultural area, East China.
AB - Hexachlorobutadiene (HCBD) is a potential persistent organic pollutant that has
been found in abiotic environments and organisms. However, information on HCBD in
soils and its accumulation in terrestrial food chains is scarce. This study
investigated the accumulation of HCBD in soils, plants, and terrestrial fauna in
a typical agricultural area in Eastern China, and drew comparisons with
organochlorine pesticides (OCPs). The HCBD concentrations in soils were <0.02
3.1ng/g dry weight, which were similar to alpha-endosulfan concentrations but
much lower than the concentrations of some other OCPs. The HCBD soil-plant
accumulation factors, 8.5-38.1, were similar to those of o,p'-DDT and higher than
those of HCHs and p,p'-DDT, indicating that HCBD is strongly bioaccumulated by
rice and vegetables. HCBD concentrations of 1.3-8.2ng/g lipid weight were found
in herbivorous insects, earthworms, and Chinese toads. The biomagnification
factor, the ratio between the lipid-normalized concentrations in the predator and
the prey, was found to be 0.16-0.64 for different food chains of Chinese toads,
so HCBD was found not to biomagnify, which is in contrast with OCPs. Further
research into whether HCBD is biomagnified in high trophic level organisms or
through the entire terrestrial food web is required.
PMID- 25124676
TI - Anti-C1q antibodies in systemic lupus erythematosus.
AB - OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE)
and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE
(vs rheumatic disease controls) and the association with SLE manifestations in an
international multicenter study. METHODS: Information and blood samples were
obtained in a cross-sectional study from patients with SLE (n = 308) and other
rheumatologic diseases (n = 389) from 25 clinical sites (84% female, 68%
Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the
collagen-like region was measured by ELISA. RESULTS: Prevalence of anti-C1q was
28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI:
1.8-4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI:
1.7-5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2-5.4, p = 0.015), anti
dsDNA (OR = 3.4, 95% CI: 1.9-6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI:
1.5-5.0, p = 0.01). Anti-C1q was independently associated with renal involvement
after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3,
95% CI: 1.3-4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low
complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8
38.4, p < 0.01). CONCLUSIONS: Anti-C1q was more common in patients with SLE and
those of Asian race/ethnicity. We confirmed a significant association of anti-C1q
with renal involvement, independent of demographics and other serologies. Anti
C1q in combination with anti-dsDNA and low complement was the strongest
serological association with renal involvement. These data support the usefulness
of anti-C1q in SLE, especially in lupus nephritis.
PMID- 25124680
TI - Proteomics study of silver nanoparticles toxicity on Oryza sativa L.
AB - The increasing use of silver nanoparticles, (AgNPs), will inevitably result in
their release into the environment and thereby cause the exposure to plants. It
was claimed that using AgNPs is a safe and efficient method to preserve and treat
agents of disease in agriculture. This study tries to understand the protein
populations and sub-populations and follow up environmental AgNPs stresses. To
accomplish these, the action of homemade spherical AgNPs colloidal suspension
against Oryza sativa L. was investigated by a proteomic approach (2-DE and
NanoLC/FT-ICR MS identification). Twenty-eight responsive (decrement/increment in
abundance) proteins were identified. Proteomic results revealed that an exposure
of O. sativa L., root with different concentrations of AgNPs resulted in an
accumulation of protein precursors, indicative of the dissipation of a proton
motive force. The identified proteins are involved in oxidative stress tolerance,
Ca(2+) regulation and signaling, transcription and protein degradation, cell wall
and DNA/RNA/protein direct damage, cell division and apoptosis. The expression
pattern of these proteins and their possible involvement in the nontoxicity
mechanisms were discussed.
PMID- 25124682
TI - Mild to Moderate Renal Impairment Is Associated With No-Reflow Phenomenon After
Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction.
AB - We investigated whether admission estimated glomerular filtration rate (eGFR)
values are associated with no-reflow phenomenon in patients with ST-segment
elevation myocardial infarction (STEMI) treated with primary percutaneous
coronary intervention (pPCI). Patients (n = 673; 59 +/- 13 years; 77.1% men) were
stratified into 3 groups according to eGFR at admission: normal renal function
(eGFR >= 90 mL/min/1.73 m2), mild renal impairment (eGFR 60-89 mL/min/1.73 m2),
and moderate renal impairment (eGFR 30-59 mL/min/1.73 m2). No-reflow phenomenon
was defined as thrombolysis in myocardial infarction flow grade <3 after pPCI.
The rate of no-reflow gradually increased from the normal renal function group to
the moderate impaired renal function group (P < .001). Multivariate analysis
showed that eGFR (odds ratio [OR] 0.942, P < .001), Killip >=2 class (OR 3.968, P
= .008), left ventricular ejection fraction (OR 0.959, P = .034), and early
patency of infarct vessel (OR 0.186, P < .001) were independent predictors of no
reflow phenomenon. Mild to moderate renal impairment at admission is
independently associated with no-reflow phenomenon after pPCI.
PMID- 25124681
TI - The miR-379/miR-410 cluster at the imprinted Dlk1-Dio3 domain controls neonatal
metabolic adaptation.
AB - In mammals, birth entails complex metabolic adjustments essential for neonatal
survival. Using a mouse knockout model, we identify crucial biological roles for
the miR-379/miR-410 cluster within the imprinted Dlk1-Dio3 region during this
metabolic transition. The miR-379/miR-410 locus, also named C14MC in humans, is
the largest known placental mammal-specific miRNA cluster, whose 39 miRNA genes
are expressed only from the maternal allele. We found that heterozygote pups with
a maternal--but not paternal--deletion of the miRNA cluster display partially
penetrant neonatal lethality with defects in the maintenance of energy
homeostasis. This maladaptive metabolic response is caused, at least in part, by
profound changes in the activation of the neonatal hepatic gene expression
program, pointing to as yet unidentified regulatory pathways that govern this
crucial metabolic transition in the newborn's liver. Not only does our study
highlight the physiological importance of miRNA genes that recently evolved in
placental mammal lineages but it also unveils additional layers of RNA-mediated
gene regulation at the Dlk1-Dio3 domain that impose parent-of-origin effects on
metabolic control at birth and have likely contributed to mammal evolution.
PMID- 25124683
TI - The effect of bupropion XL and escitalopram on memory and functional outcomes in
adults with major depressive disorder: results from a randomized controlled
trial.
AB - Decrements in cognitive function are a common feature of Major Depressive
Disorder (MDD), and whether distinct classes of antidepressants differentially
affect memory in these individuals has not been sufficiently evaluated. In this
study we sought to determine the effect of escitalopram and bupropion XL on
memory and psychosocial function. Forty-one individuals (18-50 years) with MDD
were enrolled in an 8-week, double-blind, double-dummy, randomized controlled
comparative trial of bupropion XL and escitalopram. Thirty-six participants
completed pre and post memory assessments. Verbal, non-verbal and working memory
were evaluated with a comprehensive neuropsychological battery. Psychosocial
function was assessed with the Sheehan Disability Scale and Endicott Work
Productivity Scale. Escitalopram and bupropion XL significantly improved
immediate as well as delayed verbal and nonverbal memory, global function (all
p<=0.001), and work productivity (p=0.045), with no significant between-group
differences. Improvement in immediate verbal memory exerted a direct influence on
improvement in global function (p=0.006). Treatment with either escitalopram or
bupropion XL was associated with improvement in memory and psychosocial function
in adults with MDD.
PMID- 25124684
TI - Daily life evidence of environment-incongruent emotion in schizophrenia.
AB - Researchers have recently hypothesized that negative emotion in positive
situations may be one mechanism for understanding emotion dysfunction in
schizophrenia. Using ecological momentary assessment, we examined the
relationship between emotion experience and environmental context in the daily
lives of participants with and without schizophrenia. Participants with (n=47)
and without schizophrenia (n=41) were provided a cellular telephone and called
four times a day for one week. During each call participants rated their emotion
experiences, described their current activities, and rated enjoyment from those
activities. In line with previous research, participants with schizophrenia
reported higher negative emotion overall relative to participants without
schizophrenia, but equivalent levels of positive emotion and activity enjoyment.
In line with the environment-incongruent negative emotion hypothesis,
participants with schizophrenia evidenced a weaker relationship between reported
enjoyment of current activities and current negative emotion compared to
participants without schizophrenia. In addition, lower neurocognition predicted
this weak relationship between negative emotion and context in the schizophrenia
group. These findings provide ecologically valid support for environment
incongruent negative emotion in schizophrenia, and suggest that people with
schizophrenia with more impaired neurocognition may have more difficulties
regulating negative emotion.
PMID- 25124686
TI - Low PIAS3 expression in malignant mesothelioma is associated with increased STAT3
activation and poor patient survival.
AB - PURPOSE: Deregulation of STAT3 activation is a hallmark of many cancer cells, and
the underlying mechanisms are subject to intense investigation. We examined the
extent of PIAS3 expression in mesothelioma cells and human tumor samples and
determined the functional effects of PIAS3 expression on STAT3 signaling.
EXPERIMENTAL DESIGN: We evaluated the expression of PIAS3 in mesothelioma tumors
from patients and correlated the expression levels with the course of the
disease. We also measured the effects of enhanced PIAS3 activity on STAT3
signaling, cellular growth, and viability in cultured mesothelioma cells.
RESULTS: Gene expression databases revealed that mesotheliomas have the lowest
levels of PIAS3 transcripts among solid tumors. PIAS3 expression in human
mesothelioma tumors is significantly correlated with overall survival intervals
(P = 0.058). The high expression of PIAS3 is predictive of a favorable prognosis
and decreases the probability of death within one year after diagnosis by 44%.
PIAS3 expression is functionally linked to STAT3 activation in mesothelioma cell
lines. STAT3 downregulation with siRNA or enhanced expression of PIAS3 both
inhibited mesothelioma cell growth and induced apoptosis. Mesothelioma cells are
sensitive to curcumin and respond by the induction of PIAS3. Corroborative
evidence has been obtained from STAT3 inhibition experiments. Exposure of the
cells to a peptide derived from the PIAS3 protein that interferes with STAT3
function resulted in apoptosis induction and the inhibition of cell growth.
CONCLUSION: These results suggest that PIAS3 protein expression impacts survival
in patients with mesothelioma and that PIAS3 activation could become a
therapeutic strategy. Clin Cancer Res; 20(19); 5124-32. (c)2014 AACR.
PMID- 25124687
TI - Prolongation of overall survival in advanced lung adenocarcinoma patients with
the XAGE1 (GAGED2a) antibody.
AB - PURPOSE: The cancer/testis antigen XAGE1 (GAGED2a) is expressed in approximately
40% of advanced lung adenocarcinomas. We investigated the clinical relevance of
the XAGE1 (GAGED2a) immune responses in patients with advanced lung
adenocarcinoma. EXPERIMENTAL DESIGN: The XAGE1 (GAGED2a) antigen expression and
EGFR mutation were determined with tumor tissues. The XAGE1 (GAGED2a) antibody
and T-cell immune responses, as well as immune cell phenotypes, were analyzed
with blood samples. Patients with EGFR wild-type (EGFRwt) tumors were treated
with conventional platinum-based doublet chemotherapy and patients with EGFR
mutated (EGFRmt) tumors were treated with EGFR-TKI and conventional chemotherapy.
The overall survival (OS) rates of the antibody-positive and -negative patients
were investigated. RESULTS: The results showed that the OS of antibody-positive
patients was prolonged significantly compared with that of antibody-negative
patients with either XAGE1 (GAGED2a) antigen-positive EGFRwt (31.5 vs. 15.6
months, P = 0.05) or EGFRmt (34.7 vs. 11.1 months, P = 0.001) tumors.
Multivariate analysis showed that the presence of the XAGE1 (GAGED2a) antibody
was a strong predictor for prolonged OS in patients with XAGE1 (GAGED2a) antigen
positive tumors and in patients with either EGFRwt or EGFRmt tumors. On the other
hand, XAGE1 (GAGED2a) antigen expression was a worse predictor in patients with
EGFRmt tumors. Phenotypic and functional analyses of T cells indicated immune
activation in the antibody-positive patients. CONCLUSIONS: The findings suggest
that production of the XAGE1 (GAGED2a) antibody predicts good prognosis for
patients with lung adenocarcinoma as an immune biomarker and the protective
effect of this naturally occurring immune response supports the concept of
immunotherapy.
PMID- 25124685
TI - Clinical implications of phosphorylated STAT3 expression in De Novo diffuse large
B-cell lymphoma.
AB - PURPOSE: Activated signal transducer and activator of transcription 3 (STAT3)
regulates tumor growth, invasion, cell proliferation, angiogenesis, immune
response, and survival. Data regarding expression of phosphorylated (activated)
STAT3 in diffuse large B-cell lymphoma (DLBCL) and the impact of phosphorylated
STAT3 (pSTAT3) on prognosis are limited. EXPERIMENTAL DESIGN: We evaluated
expression of pSTAT3 in de novo DLBCL using immunohistochemistry, gene expression
profiling (GEP), and gene set enrichment analysis (GSEA). Results were analyzed
in correlation with cell-of-origin (COO), critical lymphoma biomarkers, and
genetic translocations. RESULTS: pSTAT3 expression was observed in 16% of DLBCL
and was associated with advanced stage, multiple extranodal sites of involvement,
activated B-cell-like (ABC) subtype, MYC expression, and MYC/BCL2 expression.
Expression of pSTAT3 predicted inferior overall survival (OS) and progression
free survival (PFS) in patients with de novo DLBCL. When DLBCL cases were
stratified according to COO or MYC expression, pSTAT3 expression did not predict
inferior outcome, respectively. Multivariate analysis showed that the prognostic
predictability of pSTAT3 expression was due to its association with the ABC
subtype, MYC expression, and adverse clinical features. GEP demonstrated
upregulation of genes, which can potentiate function of STAT3. GSEA showed the
JAK-STAT pathway to be enriched in pSTAT3(+) DLBCL. CONCLUSIONS: The results of
this study provide a rationale for the ongoing successful clinical trials
targeting the JAK-STAT pathway in DLBCL.
PMID- 25124689
TI - Matrix metalloproteinase (MMP)-2 and MMP-9 as inflammation markers of Trichinella
spiralis and Trichinella pseudospiralis infections in mice.
AB - Trichinella spiralis and Trichinella pseudospiralis exhibit differences in the
host-parasite relationship such as the inflammatory response in parasitized
muscles. Several studies indicate that matrix metalloproteinases (MMPs) represent
a marker of inflammation since they regulate inflammation and immunity. The aim
of this study was to evaluate the serum levels of gelatinases (MMP-9 and MMP-2)
in mice experimentally infected with T. spiralis or T. pseudospiralis, to
elucidate the involvement of these molecules during the inflammatory response to
these parasites. Gelatin zymography on SDS polyacrilamide gels was used to assess
the serum levels and in situ zymography on muscle histological sections to show
the gelatinase-positive cells. In T. spiralis infected mice, the total MMP-9
serum level increased 6 days post-infection whereas, the total MMP-2 serum level
increased onward. A similar trend was observed in T. pseudospiralis infected mice
but the MMP-9 level was lower than that detected in T. spiralis infected mice.
Significant differences were also observed in MMP-2 levels between the two
experimental groups. The number of gelatinase positive cells was higher in T.
spiralis than in T. pseudospiralis infected muscles. We conclude that MMP-9 and
MMP-2 are markers of the inflammatory response for both T. spiralis and T.
pseudospiralis infections.
PMID- 25124688
TI - A recombinant modified vaccinia ankara vaccine encoding Epstein-Barr Virus (EBV)
target antigens: a phase I trial in UK patients with EBV-positive cancer.
AB - PURPOSE: Epstein-Barr virus (EBV) is associated with several cancers in which the
tumor cells express EBV antigens EBNA1 and LMP2. A therapeutic vaccine comprising
a recombinant vaccinia virus, MVA-EL, was designed to boost immunity to these
tumor antigens. A phase I trial was conducted to demonstrate the safety and
immunogenicity of MVA-EL across a range of doses. EXPERIMENTAL DESIGN: Sixteen
patients in the United Kingdom (UK) with EBV-positive nasopharyngeal carcinoma
(NPC) received three intradermal vaccinations of MVA-EL at 3-weekly intervals at
dose levels between 5 * 10(7) and 5 * 10(8) plaque-forming units (pfu). Blood
samples were taken at screening, after each vaccine cycle, and during the post
vaccination period. T-cell responses were measured using IFNgamma ELISpot assays
with overlapping EBNA1/LMP2 peptide mixes or HLA-matched epitope peptides.
Polychromatic flow cytometry was used to characterize functionally responsive T
cell populations. RESULTS: Vaccination was generally well tolerated. Immunity
increased after vaccination to at least one antigen in 8 of 14 patients (7/14,
EBNA1; 6/14, LMP2), including recognition of epitopes that vary between EBV
strains associated with different ethnic groups. Immunophenotypic analysis
revealed that vaccination induced differentiation and functional diversification
of responsive T-cell populations specific for EBNA1 and LMP2 within the CD4 and
CD8 compartments, respectively. CONCLUSIONS: MVA-EL is safe and immunogenic
across diverse ethnicities and thus suitable for use in trials against different
EBV-positive cancers globally as well as in South-East Asia where NPC is most
common. The highest dose (5 * 10(8) pfu) is recommended for investigation in
current phase IB and II trials.
PMID- 25124690
TI - PI3P phosphatase activity is required for autophagosome maturation and
autolysosome formation.
AB - Autophagosome formation is promoted by the PI3 kinase complex and negatively
regulated by myotubularin phosphatases, indicating that regulation of local
phosphatidylinositol 3-phosphate (PtdIns3P) levels is important for this early
phase of autophagy. Here, we show that the Caenorhabditis elegans myotubularin
phosphatase MTM-3 catalyzes PtdIns3P turnover late in autophagy. MTM-3 acts
downstream of the ATG-2/EPG-6 complex and upstream of EPG-5 to promote
autophagosome maturation into autolysosomes. MTM-3 is recruited to autophagosomes
by PtdIns3P, and loss of MTM-3 causes increased autophagic association of ATG-18
in a PtdIns3P-dependent manner. Our data reveal critical roles of PtdIns3P
turnover in autophagosome maturation and/or autolysosome formation.
PMID- 25124691
TI - Identification of previously undiagnosed diabetes and prediabetes in the
inpatient setting using risk factor and hemoglobin A1C screening.
AB - BACKGROUND: Identifying diabetes early in its progression can present
opportunities to intervene with education and medical management to prevent
diabetes-related complications. OBJECTIVE: The primary objective was to determine
the incidence of diabetes in hospitalized patients without insurance or routine
outpatient care using recommendations by the American Diabetes Association (ADA)
Standards of Medical Care in Diabetes for diabetes risk screening and diagnosis.
METHODS: This study was conducted at a community hospital in Abilene, Texas.
Hospitalized patients were screened if they had self-payer status and did not
have a primary care physician. If patients met screening criteria based on risk
factors listed in the ADA guidelines, a hemoglobin A1C test and fasting plasma
glucose test were completed during hospitalization. Patients found to have
diabetes were referred for outpatient education and management of diabetes. Data
to determine the incidence of diabetes diagnosis were collected retrospectively.
RESULTS: A total of 460 patients were screened for inclusion. Of the 92 patients
included in the analysis, 8.7% (n=8) were identified as having diabetes and 39.1%
(n=36) with prediabetes. Age and hypertension were independently positively
correlated with increased risk for diabetes (P=0.002; P=0.045). CONCLUSIONS:
Using risk factor screening based on ADA recommendations in the inpatient setting
did not identify a significant number of patients with diabetes. This study found
specific risk factors to be correlated with diagnosis of diabetes. Rather than
using routine screening based on the number of risk factors, the presence of
highly correlated risk factors may be an indication for diabetes screening.
PMID- 25124692
TI - Long-term effectiveness of supported employment: 5-year follow-up of a randomized
controlled trial.
AB - OBJECTIVE: The individual placement and support model of supported employment has
been shown to be more effective than other vocational approaches in improving
competitive work over 1-2 years in persons with severe mental illness. The
authors evaluated the longer-term effects of the model compared with traditional
vocational rehabilitation over 5 years. METHOD: A randomized controlled trial
compared supported employment to traditional vocational rehabilitation in 100
unemployed persons with severe mental illness. Competitive work and hospital
admissions were tracked for 5 years, and interviews were conducted at 2 and 5
years to assess recovery attitudes and quality of life. A cost-benefit analysis
compared program and total treatment costs to earnings from competitive
employment. RESULTS: The beneficial effects of supported employment on work at 2
years were sustained over the 5-year follow-up period. Participants in supported
employment were more likely to obtain competitive work than those in traditional
vocational rehabilitation (65% compared with 33%), worked more hours and weeks,
earned more wages, and had longer job tenures. Reliance on supported employment
services for retaining competitive work decreased from 2 years to 5 years for
participants in supported employment. Participants were also significantly less
likely to be hospitalized, had fewer psychiatric hospital admissions, and spent
fewer days in the hospital. The social return on investment was higher for
supported employment participants, whether calculated as the ratio of work
earnings to vocational program costs or of work earnings to total vocational
program and mental health treatment costs. CONCLUSIONS: The results demonstrate
that the greater effectiveness of supported employment in improving competitive
work outcomes is sustained beyond 2 years and suggest that supported employment
programs contribute to reduced hospitalizations and produce a higher social
return on investment.
PMID- 25124693
TI - Extranodal natural killer/T-cell lymphoma nasal type: detection by computed
tomography features.
AB - OBJECTIVES/HYPOTHESIS: Nasal natural killer/T-cell lymphoma (NKTL) often has an
infiltrative pattern in computed tomography that makes them difficult to
distinguish from benign inflammatory diseases. This study aimed to design a
method of measuring the thickness of the nasal floor and nasal septum, determine
the critical value of mucosal thickness that may implicate these NKTL cases from
benign inflammatory disease, and finally make a complete flowchart to detect NKTL
with minimal mistake. STUDY DESIGN: Thirty-two patients with nasal NKTL and 173
patients with severe chronic rhinosinusitis with or without polyposis were
enrolled. The patients' data were collected retrospectively. METHODS: All
patients underwent standard computed tomography of the paranasal sinuses. The
coronal section near the vertical part of the ground lamina was chosen for
measurement, and the thickest points along the nasal floor and septum were
measured. RESULTS: Patients with NKTL had thicker nasal floors and/or septa than
those with chronic rhinosinusitis, recurrent sinusitis, or pansinusitis (P <
.001). If the cutoff points of the nasal floor and nasal septum thickness were
set at 2.0 mm and 2.5 mm, respectively, the probability of being thicker than the
corresponding points in the CRS group was <2%, and the possibility of other
diagnoses should be considered. CONCLUSIONS: Nasal floor mucosal thickness >2.0
mm or nasal septum mucosal thickness >2.5 mm may be indicators serving as one of
several important hints for implicit NKTL. Finally, we established a diagnostic
flowchart to include all of these important hints. LEVEL OF EVIDENCE: 4.
PMID- 25124694
TI - Dynamic behaviors of approximately ellipsoidal microbubbles photothermally
generated by a graphene oxide-microheater.
AB - Thermal microbubbles generally grow directly from the heater and are spherical to
minimize surface tension. We demonstrate a novel type of microbubble indirectly
generated from a graphene oxide-microheater. Graphene oxide's photothermal
properties allowed for efficient generation of a thermal gradient field on the
microscale. A series of approximately ellipsoidal microbubbles were generated on
the smooth microwire based on heterogeneous nucleation. Other dynamic behaviors
induced by the microheater such as constant growth, directional transport and
coalescence were also investigated experimentally and theoretically. The results
are not only helpful for understanding the bubble dynamics but also useful for
developing novel photothermal bubble-based devices.
PMID- 25124695
TI - Prevention of behavior problems in a selected population: Stepping stones triple
P for parents of young children with disabilities.
AB - Because young children with disabilities are at elevated risk for development of
challenging behaviors, and caregivers of these children typically lack access to
evidence-based parenting interventions, two randomized trials were conducted to
examine the impact of an evidence-based parenting intervention, Stepping Stones
Triple P (SSTP), as a selective preventive intervention. Both studies targeted
parents of children under two with a variety of disabilities who were enrolled in
the IDEA Part C Early Intervention (EI) system in one state. SSTP was delivered
in family homes. In Study One, 49 families were randomly assigned to EI services
as usual, with or without SSTP; a 52% attrition rate from treatment was seen. No
significant between-group differences were seen aside from a trend toward reduced
symptoms of parental depression at follow-up. Intervention group children
demonstrated significant decline in behavior problems from post treatment to
follow-up, and there was a trend toward improved parenting style in the
intervention group during this same time frame. Study Two incorporated a separate
workforce intervention for EI service coordinators; 40 families on their
caseloads were then randomly assigned to receive EI services as usual with or
without SSTP. Attrition from treatment was limited to 20%. No differential impact
was seen on child behavior; a trend was noted post-treatment on parent symptoms
of depression and on the observed parent-child relationship. At 12-month follow
up, there was a trend favoring improvement in the intervention group in parenting
style; statistically significant impact was also seen on the observed quality of
the parent-child relationship. SSTP shows promise as a selective preventive
intervention for an early intervention population. Reasons for the differential
findings between the two studies are explored and suggestions for future research
are provided.
PMID- 25124696
TI - Recent insights into genotype-phenotype relationships in patients with Rett
syndrome using a fine grain scale.
AB - Mutations in MECP2 gene cause Rett syndrome (RTT), a neurodevelopmental disorder
affecting around 1 in 10,000 female births. The clinical picture of RTT appears
quite heterogeneous for each single feature. Mutations in MECP2 gene have been
associated with the onset of RTT. The most known gene function consists of
transcriptional repression of specific target genes, mainly by the binding of its
methyl binding domain (MBD) to methylated CpG nucleotides and recruiting co
repressors and histone deacetylase binding to DNA by its transcription repressor
domain (TRD). This study aimed at evaluating a cohort of 114 Rett syndrome (RTT)
patients with a detailed scale measuring the different kinds of impairments
produced by the syndrome. The sample included relatively large subsets of the
most frequent mutations, so that genotype-phenotype correlations could be tested.
Results revealed that frequent missense mutations showed a specific profile in
different areas of impairment. The R306C mutation, considered as producing mild
impairment, was associated to a moderate phenotype in which behavioural
characteristics were mainly affected. A notable difference emerged by comparing
mutations truncating the protein before and after the nuclear localization
signal; such a difference concerned prevalently the motor-functional and autonomy
skills of the patients, affecting the management of everyday activities.
PMID- 25124698
TI - Arithmetic strategy development and its domain-specific and domain-general
cognitive correlates: a longitudinal study in children with persistent
mathematical learning difficulties.
AB - Deficits in arithmetic fact retrieval constitute the hallmark of children with
mathematical learning difficulties (MLD). It remains, however, unclear which
cognitive deficits underpin these difficulties in arithmetic fact retrieval. Many
prior studies defined MLD by considering low achievement criteria and not by
additionally taking the persistence of the MLD into account. Therefore, the
present longitudinal study contrasted children with persistent MLD (MLD-p; mean
age: 9 years 2 months) and typically developing (TD) children (mean age: 9 years
6 months) at three time points, to explore whether differences in arithmetic
strategy development were associated with differences in numerical magnitude
processing, working memory and phonological processing. Our longitudinal data
revealed that children with MLD-p had persistent arithmetic fact retrieval
deficits at each time point. Children with MLD-p showed persistent impairments in
symbolic, but not in nonsymbolic, magnitude processing at each time point. The
two groups differed in phonological processing, but not in working memory. Our
data indicate that both domain-specific and domain-general cognitive abilities
contribute to individual differences in children's arithmetic strategy
development, and that the symbolic processing of numerical magnitudes might be a
particular risk factor for children with MLD-p.
PMID- 25124699
TI - To evaluate the effects of a simplified hand washing improvement program in
schoolchildren with mild intellectual disability: a pilot study.
AB - A quasi-experimental study using a pretest-posttest design with a control group
was used to evaluate the effects of a simplified 5-step multimedia visualization
hand hygiene improvement program by schoolchildren with mild intellectual
disability (MID). A total of twenty schoolchildren aged 6-12 years old with MID
(12 males) were recruited and they were assigned into intervention (n=10) and
control (n=10) groups. To evaluate the quality of their hand washing, Glow gel,
which contains plastic simulated germs that are visible under an ultra-violet
lamp, was applied to participants' hands to assess the quality of hand washing by
comparing the amount of visible Glow gel before and after hand washing using a 4
point scale. Four raters used this 4-point scale to assess the quality of hand
washing through digital photo images of the participants' hands. A total of eight
digital photos per participant were taken. A fifteen-minute hand washing training
session was conducted every school day for 4 weeks for the intervention group.
Those in the control group received no training. A multimedia visual package on
steps of hand washing was presented together with a reward system, whereby a
number of stars were earned each week depending on the quality of hand washing.
Results showed encouraging findings, as the schoolchildren in the intervention
group showed significant improvement in hand washing (p<0.001) and the
improvement was stronger than that of the control group (p=0.02). To conclude, a
systematic instruction emphasizing multimedia visualization in a hand washing
improvement program can be successfully implemented in a special school, and the
effect of integrating multimedia visuals in the hand hygiene program could
improve hand hygiene among schoolchildren with MID.
PMID- 25124697
TI - Metabolomic (anthropometric and biochemical) indexes and metabolic syndrome in
adolescents and young adults with intellectual disabilities.
AB - The aim of the present study was to describe the use of combination of
international standardized anthropometric parameters, along with biochemical
parameters (metabolomic indexes) to identify metabolic syndrome (MetS), in
persons with intellectual disabilities. We conducted a cross-sectional study of
42 adolescents and young adults with intellectual disabilities (aged 13-30years)
who attend special schools in Ciudad Juarez, Chihuahua, Mexico. The study
included anthropometric (using the International Society for the Advancement of
Kineanthropometry recommendations) and biochemical measures, and their
combinations as metabolomic-indexes, that can significantly predict MetS
occurrence in this vulnerable population. Waist circumference (WC) and relaxed
arm circumference, both adjusted for height, have the highest correlation with
MetS (R2=0.23-0.47, p<0.01). Besides body mass index (BMI) and WC we propose
other indicators such as, skinfolds, hip circumference and relaxed arm
circumference, all of them adjusted by height in order to better define the
presence of MetS in persons with intellectual disabilities.
PMID- 25124700
TI - A computer-aided program for helping patients with moderate Alzheimer's disease
engage in verbal reminiscence.
AB - This study assessed a simple computer-aided program for helping patients with
moderate Alzheimer's disease engage in verbal reminiscence. In practice, the
program was aimed at fostering the patient's verbal engagement on a number of
life experiences/topics previously selected for him or her and introduced in the
sessions through a friendly female, who appeared on the computer screen. The
female asked the patient about the aforementioned experiences/topics, and
provided him or her with positive attention, and possibly verbal guidance (i.e.,
prompts/encouragements). Eight patients were involved in the study, which was
carried out according to non-concurrent multiple baseline designs across
participants. Seven of them showed clear improvement during the intervention
phase (i.e., with the program). Their mean percentages of intervals with verbal
engagement/reminiscence ranged from close to zero to about 15 during the baseline
and from above 50 to above 75 during the intervention. The results were discussed
in relation to previous literature on reminiscence therapy, with specific
emphasis on the need for (a) replication studies and (b) the development of new
versions of the technology-aided program to improve its impact and reach a wider
number of patients.
PMID- 25124702
TI - Effects of 1,25-dihydroxyvitamin D3 on human epidermal melanocytes and
melanoblasts.
PMID- 25124701
TI - A pilot study of angiogenin in heart failure with preserved ejection fraction: a
novel potential biomarker for diagnosis and prognosis?
AB - Characteristics of heart failure with preserved ejection fraction (HFPEF) have
not yet been fully understood. The objectives of this pilot study are to detect
protein expression profile in the sera of HFPEF patients, and to identify
potential biomarkers for the disease. Five hundred and seven proteins were
detected in the sera of healthy volunteers and patients with either HFPEF or
hypertension using antibody microarrays (three in each group). The results showed
that the serum concentrations of 17 proteins (e.g. angiogenin, activin A and
artemin) differed considerably between HFPEF and non-HFPEF patients (hypertensive
patients and healthy controls), while a protein expression pattern distinct from
that in non-HFPEF patients was associated with HFPEF patients. The up-regulation
of angiogenin in both HFPEF patients with LVEF >=50% (P = 0.004) and a subset of
HFPEF patients with LVEF = 41-49% (P < 0.001) was further validated in 16 HFPEF
patients and 16 healthy controls. Meanwhile, angiogenin distinguished HFPEF
patients from controls with a mean area under the receiver operating
characteristic curve of 0.88 (P < 0.001) and a diagnostic cut-off point of 426
ng/ml. Moreover, the angiogenin levels in HFPEF patients were positively
correlated with Lg(N-terminal pro-B-type natriuretic peptide, NT-proBNP) (P <
0.001). In addition, high angiogenin level (>=426 ng/ml) was a predictor of all
cause death within a short-term follow-up duration, but not in the longer term of
36 months. This pilot study indicates that the aforementioned 17 potential
biomarkers, such as angiogenin, may hold great promise for both diagnosis and
prognosis assessment of HFPEF.
PMID- 25124703
TI - Identification and characterization of human Rad51 inhibitors by screening of an
existing drug library.
AB - Homologous Recombination (HR) plays an essential role in cellular proliferation
and in maintaining genomic stability by repairing DNA double-stranded breaks that
appear during replication. Rad51, a key protein of HR in eukaryotes, can have an
elevated expression level in tumor cells, which correlates with their resistance
to anticancer therapies. Therefore, targeted inhibition of Rad51 through
inhibitor may improve the tumor response to these therapies. In order to identify
small molecules that inhibit Rad51 activity, we screened the Prestwick Library
(1120 molecules) for their effect on the strand exchange reaction catalyzed by
Rad51. We found that Chicago Sky Blue (CSB) is a potent inhibitor of Rad51,
showing IC50 values in the low nanomolar range (400 nM). Biochemical analysis
demonstrated that the inhibitory mechanism probably occurs by disrupting the
Rad51 association with the single-stranded DNA, which prevents the nucleoprotein
filament formation, the first step of the protein activity. Structure Activity
Relationship analysis with a number of compounds that shared structure homology
with CSB was also performed. The sensitivity of Rad51 inhibition to CSB
modifications suggests specific interactions between the molecule and Rad51
nucleofilament. CSB and some of its analogs open up new perspectives in the
search for agents capable of potentiating chemo- and radio-therapy treatments for
cancer. Moreover, these compounds may be excellent tools to analyze Rad51
cellular functions. Our study also highlights how CSB and its analogs, which are
frequently used in colorants, stains and markers, could be responsible of
unwanted side effects by perturbing the DNA repair process.
PMID- 25124705
TI - Local anesthetic versus forced coughing at colposcopic-guided biopsy: a
prospective study.
AB - OBJECTIVE: To evaluate whether the administration of local anesthetic (LA)
reduces pain in comparison with forced coughing (FC) for the execution of
colposcopically guided biopsies (CGBs). STUDY DESIGN: Data of 100 consecutive
patients undergoing CGBs with the use of LA or FC were prospectively evaluated.
Procedure-related pain was assessed with the use of a 100-mm visual analogue
scale. RESULTS: Fifty-one and 49 patients had CGBs using LA and FC, respectively.
No between-group differences were observed in terms of pain related to speculum
insertion, CGBs and pain recorded after the procedures (p>0.05). However,
patients in the LA group experienced pain related to cervical injection for
administration of anesthesia (mean (+/-SD): 12.4 (+/-1.6)). Operative time was
longer in the LA than in the FC group (7.2 (+/-0.2) vs. 5.0 (+/-0.1)min;
p<0.001). CONCLUSIONS: FC should be preferred over LA. Although CGB-related pain
levels do not differ, the omission of intracervical injection is associated with
undoubted advantages.
PMID- 25124706
TI - A review of stroke and pregnancy: incidence, management and prevention.
AB - Stroke, defined as a focal or global disturbance of cerebral function lasting
over 24h resulting from disruption of its blood supply, is a devastating event
for a pregnant woman. This can result in long-term disability or death, and
impact on her family and unborn child. In addition to pre-existing patient risk
factors, the hypercoagulable state and pre-eclampsia need to be taken into
account. The patterns and types of stroke affect pregnant women differ from the
non-pregnant female population of child-bearing age. Like other thrombo-embolic
diseases in pregnancy, stroke is essentially a disease of the puerperium.
Population studies have estimated the risk of stroke at between 21.2 and 46.2 per
100,000. The US Nationwide Inpatient Sample, identified 2850 pregnancies
complicated by stroke in the United States in 2000-2001, for a rate of 34.2 per
100,000 deliveries. There were 117 deaths, a mortality rate of 1.4 per 100,000.
Both the mortality and disability rates were higher than previously reported,
with 10-13% of women dying. With the increasing prevalence of obesity,
hypertension and cardiac disease amongst women of child-bearing age, so is the
incidence of stroke during pregnancy and the puerperium. In the United States, an
alarming trend toward higher numbers of stroke hospitalizations during the last
decade was demonstrated in studies from 1995 to 1996 and 2006 to 2007. The rate
of all types of stroke increased by 47% among antenatal hospitalizations, and by
83% among post-partum hospitalizations. Hypertensive disorders, obesity and heart
disease complicated 32% of antenatal admissions and 53% of post-partum
admissions. In addition to pre-existing patient risk factors, the hypercoagulable
state and pre-eclampsia need to be taken into account. The patterns and types of
stroke affect pregnant women differ from the non-pregnant female population of
child-bearing age. Like other thrombo-embolic diseases in pregnancy, stroke is
essentially a disease of the puerperium.
PMID- 25124707
TI - The influence of prolonged preterm premature rupture of the membranes on neonatal
outcome of the presenting and non-presenting twin.
AB - OBJECTIVE: To compare the neonatal outcome in twin gestations complicated by
prolonged preterm premature rupture of membranes (PPROM). STUDY DESIGN: Between
the years 2000 and 2010 we identified 48 women with twin pregnancies who were
diagnosed as having PPROM and a latency period to delivery >24h. We compared the
neonatal morbidity and mortality between the presenting and non-presenting twins,
assuming that the rupture occurred in the lower sac. Importantly, in 30 women we
were able to identify the location of the ruptured sac by ultrasound examination
demonstrating oligohydramnion. In these 30 cases, neonatal outcome of fetuses in
the ruptured sac and those in the intact sac were compared. RESULTS: The median
gestational age was 31 weeks (range 28-33) with a median latency period between
PPROM and delivery of 9 days (range 1-18). Of the identified ruptures 90% (27/30)
occurred in the lower sac (presenting twin). There was no significant difference
between the presenting and non-presenting twin in terms of neonatal morbidity and
mortality. Moreover, no difference was found when fetuses with ruptured sac were
compared to those with intact membrane sac. Importantly, the outcomes were not
affected by the length of the latency period. CONCLUSION: The current study
results demonstrated that the outcome of fetuses exposed to prolonged preterm
rupture of membranes is similar to that of fetuses with intact membranes. Our
data suggest that rupture of membranes per se did not cause any deleterious
clinical manifestations or lead to clinical discordant inflammation and poor
neonatal outcome, supporting a conservative management of twin pregnancies with
PPROM.
PMID- 25124708
TI - Vitamin C attenuates detrimental effects of diabetes mellitus on sperm
parameters, chromatin quality and rate of apoptosis in mice.
AB - OBJECTIVES: The main goal was to examine the protective effects of vitamin C on
sperm parameters, sperm chromatin condensation and apoptosis in experimentally
induced diabetic mice. STUDY DESIGN: 28 adult Syrian mice were divided into 4
groups. In Group1, the mice were diabetic that received a single dose of
Streptozocin (STZ) (200mg/kg) intra-peritoneally (ip). Group 2 was included
diabetic mice that received vitamin C (10mg/kg/daily, ip). Mice in group 3 were
received vitamin C and group 4 was considered as control. After 35 days, sperm
analysis was done accordingly. To asses sperm chromatin and DNA quality, we used
aniline blue (AB), toluidine blue (TB), chromomycin A3 (CMA3), acridine orange
(AO) and terminal transferase mediated deoxyuridine triphosphate biotin end
labeling (TUNEL) tests. RESULTS: All of the sperm parameters (count, motility,
morphology and viability) had significant reduction in diabetic mice but, the
data showed a significant increase in all of the sperm parameters in
diabetic+vitamin C when compared with diabetic and control animals (P<0.05).
There were significant differences (P<0.001) between groups regarding to TB
staining (48.8+/-5.92 vs 34.3+/-4.13), AO test (35.9+/-6.11 vs 20.8+/-2.89) and
TUNEL test (39.42+/-7.18 vs 22.00+/-3.65) in diabetic and diabetic+vitamin C
groups, respectively. Nevertheless, in CMA3 and AB staining assays, there were
not any significant differences between different groups. CONCLUSION: Vitamin C,
as a potent antioxidant, can attenuate detrimental effects of diabetes mellitus
on the sperm parameters, chromatin quality and apoptosis in an experimental
model.
PMID- 25124704
TI - Novel third-generation water-soluble noscapine analogs as superior microtubule
interfering agents with enhanced antiproliferative activity.
AB - Noscapine, an opium-derived 'kinder-gentler' microtubule-modulating drug is in
Phase I/II clinical trials for cancer chemotherapy. However, its limited water
solubility encumbers its development into an oral anticancer drug with clinical
promise. Here we report the synthesis of 9 third-generation, water-soluble
noscapine analogs with negatively charged sulfonato and positively charged
quaternary ammonium groups using noscapine, 9-bromonoscapine and 9-aminonoscapine
as scaffolds. The predictive free energy of solvation was found to be lower for
sulfonates (6a-c; 8a-c) compared to the quaternary ammonium-substituted
counterparts, explaining their higher water solubility. In addition, sulfonates
showed higher charge dispersability, which may effectively shield the
hydrophobicity of isoquinoline nucleus as indicated by hydrophobicity mapping
methods. These in silico data underscore efficient net charge balancing, which
may explain higher water solubility and thus enhanced antiproliferative efficacy
and improved bioavailability. We observed that 6b, 8b and 8c strongly inhibited
tubulin polymerization and demonstrated significant antiproliferative activity
against four cancer cell lines compared to noscapine. Molecular simulation and
docking studies of tubulin-drug complexes revealed that the brominated compound
with a four-carbon chain (4b, 6b, and 8b) showed optimal binding with tubulin
heterodimers. Interestingly, 6b, 8b and 8c treated PC-3 cells resulted in
preponderance of mitotic cells with multipolar spindle morphology, suggesting
that they stall the cell cycle. Furthermore, in vivo pharmacokinetic evaluation
of 6b, 8b and 8c revealed at least 1-2-fold improvement in their bioavailability
compared to noscapine. To our knowledge, this is the first report to demonstrate
novel water-soluble noscapine analogs that may pave the way for future pre
clinical drug development.
PMID- 25124709
TI - Toxoplasma gondii and anxiety disorders in a community-based sample.
AB - A growing body of literature suggests that exposure to the neurotropic parasite
Toxoplasma gondii (T. gondii) is associated with increased risk of mental
disorders, particularly schizophrenia. However, a potential association between
T. gondii exposure and anxiety disorders has not been rigorously explored. Here,
we examine the association of T. gondii infection with both anxiety and mood
disorders. Participants (n=484) were drawn from the Detroit Neighborhood Health
Study, a population-representative sample of Detroit residents. Logistic
regression was used to examine the associations between T. gondii exposure
(defined by seropositivity and IgG antibody levels) and three mental disorders:
generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD) and
depression. We found that T. gondii seropositivity was associated with a 2 times
greater odds of GAD (odds ratio (OR), 2.25; 95% confidence interval (CI), 1.11
4.53) after adjusting for age, gender, race, income, marital status, and
medication. Individuals in the highest antibody level category had more than 3
times higher odds of GAD (OR, 3.35; 95% CI, 1.41-7.97). Neither T. gondii
seropositivity nor IgG antibody levels was significantly associated with PTSD or
depression. Our findings indicate that T. gondii infection is strongly and
significantly associated with GAD. While prospective confirmation is needed, T.
gondii infection may play a role in the development of GAD.
PMID- 25124710
TI - A role for inflammatory metabolites as modulators of the glutamate N-methyl-D
aspartate receptor in depression and suicidality.
AB - BACKGROUND: Patients with depression and suicidality suffer from low-grade
neuroinflammation. Pro-inflammatory cytokines activate indoleamine 2,3
dioxygenase, an initial enzyme of the kynurenine pathway. This pathway produces
neuroactive metabolites, including quinolinic- and kynurenic acid, binding to the
glutamate N-methyl-d-aspartate-receptor, which is hypothesized to be part of the
neural mechanisms underlying symptoms of depression. We therefore hypothesized
that symptoms of depression and suicidality would fluctuate over time in patients
prone to suicidal behavior, depending on the degree of inflammation and
kynurenine metabolite levels in the cerebrospinal fluid (CSF). METHODS: We
measured cytokines and kynurenine metabolites in CSF, collected from suicide
attempters at repeated occasions over 2 years (total patient samples n=143,
individuals n=30) and healthy controls (n=36). The association between the
markers and psychiatric symptoms was assessed using the Montgomery Asberg
Depression Rating Scale and the Suicide Assessment Scale. RESULTS: Quinolinic
acid was increased and kynurenic acid decreased over time in suicidal patients
versus healthy controls. Furthermore, we found a significant association between
low kynurenic acid and severe depressive symptoms, as well as between high
interleukin-6 levels and more severe suicidal symptoms. CONCLUSIONS: We
demonstrate a long-term dysregulation of the kynurenine pathway in the central
nervous system of suicide attempters. An increased load of inflammatory cytokines
was coupled to more severe symptoms. We therefore suggest that patients with a
dysregulated kynurenine pathway are vulnerable to develop depressive symptoms
upon inflammatory conditions, as a result the excess production of the NMDA
receptor agonist quinolinic acid. This study provides a neurobiological framework
supporting the use of NMDA-receptor antagonists in the treatment of suicidality
and depression.
PMID- 25124711
TI - Explaining person identification: an inquiry into the tracking of human agents.
AB - To introduce the issue of the tracking and identification of human agents, I
examine the ability of an agent ("a tracker") to track a human person ("a
target") and distinguish this target from other individuals: The ability to
perform person identification. First, I discuss influential mechanistic models of
the perceptual recognition of human faces and people (the face-recognition
program). Such models propose detailed hypotheses about the parts and activities
of the mental mechanisms that control the perceptual recognition of persons.
However, models based on perceptual recognition are incomplete theories of person
identification because they do not explain several identification behaviors that
are fundamental to human social interactions (e.g., identifying unobservable
persons and imposters). Furthermore, recognition-based models tend to appeal to
the controversial concept of the "identity" of a person without explaining what
determines personal identity and persistence. To overcome these limitations, I
propose to integrate the face-recognition program into a broader causal
historical theory of identification. The causal-historical theory of
identification complements models focused on perceptual recognition because it
can account for the types of non-perceptual identification overlooked by the face
recognition program. Moreover, it can decompose the identification behaviors into
tracking processes that succeed or fail to be sensitive to causal characteristics
of a target. I illustrate these advantages with a discussion of the difference
between the tracking of a person understood as either a causally continuous
biological organism (organism-based tracking) or a psychologically continuous
mind (psychological tracking). Finally, I argue that the causal-historical theory
provides a theoretical framework for investigating the tracking of relations
between a target and its contextual and historical attributes, such as a target's
possessions.
PMID- 25124712
TI - Self medicated antibiotics in Bangladesh: a cross-sectional health survey
conducted in the Rajshahi City.
AB - BACKGROUND: Antibiotic self medication is highly prevalent in the developing
countries due to easy availability and poor regulatory controls for selling these
drugs. The purpose of this study was to evaluate the prevalence of self
medication with antibiotics for the treatment of various diseases by the peoples
of Rajshahi city in Bangladesh. METHODS: A cross-sectional survey was conducted
to the patient's (n = 1300) at eight locations of Rajshahi city in Bangladesh
from March to April, 2014. The locations were selected by convenience and the
study population within each study area was randomly selected. The survey was
self-administered and included questions pertaining to self medicated drugs and
antibiotic usage patterns as well. Data were analyzed using descriptive
statistics. RESULTS: It was found that 347 (26.69%) out of 1300 participants
experienced self medication with antibiotics. Over fifty percent of the patients
studied were between the ages of 21-30 years with 83.57% of them being males and
16.43% females. The highest percentage of self medicated antibiotics was
metronidazole (50.43%) followed by azithromycin (20.75%), ciprofloxacin (11.53%),
amoxicillin (10.37%) and tetracycline (7.49%) respectively. The key reasons for
the self medication of antibiotics was the pre-experience (45.82%), suggestions
from others (28.24%) and knowledgeable of the antibiotics (16.14%). The perceived
symptoms to purchase the antibiotics independently was dysentery, diarrhea and
food poisoning (36.02%), cold, cough and fever (28.24%), infection (12.97%),
dental carries and toothache (9.22%), irritable bowel syndrome (3.46%), acne
(4.32%), ear and throat pain (2.31%). The duration of maximum antibiotics usage
was ranges between 0-10 years. Only 4.32% patient's used self medicated
antibiotics longer than 10 years. The patient's compliance for self medication of
antibiotics varies from excellent to no comments whereas only 6.92% patients
reported side effects for the self medication of antibiotics. CONCLUSIONS: The
results of this study confirm that antibiotic self-medication is a relatively
frequent problem in Bangladesh. Drug Administration of Bangladesh should
implement the regulatory controls immediately on the distribution and selling of
antibiotics in order to reduce the frequency of antibiotic misuse.
PMID- 25124713
TI - Non-eosinophilic airway hyper-reactivity in mice, induced by IFN-gamma producing
CD4(+) and CD8(+) lung T cells, is responsive to steroid treatment.
AB - Non-eosinophilic asthma is characterized by infiltration of neutrophils into the
lung and variable responsiveness to glucocorticoids. The pathophysiological
mechanisms have not been characterized in detail. Here, we present an
experimental asthma model in mice associated with non-eosinophilic airway
inflammation and airway hyper-responsiveness (AHR). For this, BALB/c mice were
sensitized by biolistic DNA immunization with a plasmid encoding the model
antigen beta-galactosidase (pFascin-betaGal mice). For comparison, eosinophilic
airway inflammation was induced by subcutaneous injection of betaGal protein
(betaGal mice). Intranasal challenge of mice in both groups induced AHR to a
comparable extent as well as recruitment of inflammatory cells into the airways.
In contrast to betaGal mice, which exhibited extensive eosinophilic infiltration
in the lung, goblet cell hyperplasia and polarization of CD4(+) T cells into Th2
and Th17 cells, pFascin-betaGal mice showed considerable neutrophilia, but no
goblet cell hyperplasia and a predominance of Th1 and Tc1 cells in the airways.
Depletion studies in pFascin-betaGal mice revealed that CD4(+) and CD8(+) cells
cooperated to induce maximum inflammation, but that neutrophilic infiltration was
not a prerequisite for AHR induction. Treatment of pFascin-betaGal mice with
dexamethasone before intranasal challenge did not affect neutrophilic
infiltration, but significantly reduced AHR, infiltration of monocytes and
lymphocytes as well as content of IFN-gamma in the bronchoalveolar fluid. Our
results suggest that non-eosinophilic asthma associated predominantly with
Th1/Tc1 cells is susceptible to glucocorticoid treatment. pFascin-betaGal mice
might represent a mouse model to study pathophysiological mechanisms proceeding
in the subgroup of asthmatics with non-eosinophilic asthma that respond to
inhaled steroids.
PMID- 25124715
TI - Structure and development of 'witches' broom' galls in reproductive organs of
Byrsonima sericea (Malpighiaceae) and their effects on host plants.
AB - Galls are anomalies in plant development of parasitic origin that affect the
cellular differentiation or growth and represent a remarkable plant-parasite
interaction. Byrsonima sericea DC. (Malpighiaceae) is a super host of several
different types of gall in both vegetative and reproductive organs. The existence
of galls in reproductive organs and their effects on the host plant are seldom
described in the literature. In this paper, we present a novel study of galls in
plants of the Neotropical region: the 'witches' broom' galls developed in floral
structures of B. sericea. The unaffected inflorescences are characterised by a
single indeterminate main axis with spirally arranged flower buds. The flower
buds developed five unaffected brownish hairy sepals and five pairs of elliptical
yellow elaiophores, five yellow fringed petals, 10 stamens and a pistil with
superior tricarpellar and trilocular ovary. The affected inflorescences showed
changes in architecture, with branches arising from the main axis and flower
buds. The flower buds exhibited several morphological and anatomical changes. The
sepals, petals and carpels converted into leaf-like structures after
differentiation. Stamens exhibited degeneration of the sporogenous tissue and
structures containing hyphae and spores. The gynoecium did not develop, forming a
central meristematic region, from which emerges the new inflorescence. In this
work, we discuss the several changes in development of reproductive structures
caused by witches' broom galls and their effects on reproductive success of the
host plants.
PMID- 25124714
TI - ADAM10 correlates with uveal melanoma metastasis and promotes in vitro invasion.
AB - Uveal melanoma (UM) is a rare ocular tumor that may lead to deadly metastases in
50% of patients. A disintegrin and metalloproteinase (ADAM)10, ADAM17, and the
HGF-receptor c-Met support invasiveness in different tumors. Here, we report that
high ADAM10, MET, and, to a lesser extent, ADAM17 gene expression correlates with
poor progression-free survival in UM patients (hazard ratio 2.7, 2.6, and 1.9,
respectively). About 60% of primary UM expresses c-Met and/or ADAM10 proteins.
Four UM cell lines display high levels of ADAM10 and ADAM17, which constitutively
cleave c-Met, inducing the release of soluble c-Met. ADAM10/17 pharmacological
inhibition or gene silencing reduces c-Met shedding, but has limited impact on
surface c-Met, which is overexpressed. Importantly, ADAM10 silencing inhibits UM
cell invasion driven by FCS or HGF, while ADAM17 silencing has a limited effect.
Altogether our data indicate that ADAM10 has a pro-invasive role and may
contribute to UM progression.
PMID- 25124716
TI - Induced self-assembly of platinum(II) alkynyl complexes through specific
interactions between citrate and guanidinium for proof-of-principle detection of
citrate and an assay of citrate lyase.
AB - Water-soluble alkynylplatinum(II) terpyridine complexes appended with guanidinium
moieties, [Pt(tpy)(C=C-Ar)][OTf]2 (tpy=terpyridine;
OTf=trifluoromethanesulfonate; Ar=C6 H4-{NHC(=NH2(+))(NH2)}-4 (1), C6 H4-{CH2
NHC(=NH2(+))(NH2)}-4 (2)), and [Pt(tBu3 tpy)(C=CC6H4-{NHC(=NH2(+))(NH2)}
4)][OTf]2 (3; tBu3 tpy=4,4',4''-tri-tert-butyl-2,2':6',2''-terpyridine), have
been synthesized and characterized. The photophysical properties of the complexes
have been studied. Based on the results of UV/Vis absorption, resonance light
scattering, and dynamic light scattering experiments, in aqueous buffer solutions
complexes 1 and 2 undergo aggregation in the presence of citrate through strong
and specific electrostatic and hydrogen-bonding interactions with citrate. The
emergence of a triplet metal-metal-to-ligand charge transfer ((3 MMLCT) emission
in the near-infrared (NIR) region brought on by the induced self-assembly of
complex 1 has been demonstrated for proof-of-principle detection of citrate with
good sensitivity and selectivity over other mono- and dicarboxylate substrates in
the tricarboxylic acid (TCA) cycle as well as phosphate and lactate anions. Such
a good selectivity toward citrate has been rationalized by the high charge
density of citrate under physiological conditions and specific interactions
between the guanidinium moiety on complex 1 and citrate. Extension of the work to
citrate detection in fetal bovine serum and real-time monitoring of the activity
of citrate lyase by the NIR emission of complex 1 have also been demonstrated.
PMID- 25124717
TI - The cross-sectional area changes in digital flexor tendons and suspensory
ligament in foals by ultrasonographic examination.
AB - REASONS FOR PERFORMING STUDY: Flexural deformities are common conditions of
growing horses and are suggested to have a relationship with the contraction of
musculotendinous units. However, limited studies have documented the changes in
each tendon and ligament in the metacarpal region with age. OBJECTIVES: To
investigate the changes in the cross-sectional area (CSA) of each tendon and
ligament in the metacarpal region with age by ultrasonographic examination. STUDY
DESIGN: Longitudinal study of foals from Day 1 to age 24 months. METHODS: The CSA
of the superficial digital flexor tendon, deep digital flexor tendon, accessory
ligament of the deep digital flexor tendon and suspensory ligament was measured
by ultrasonographic examination at monthly intervals from Day 1 to age 24 months
in 7 Thoroughbred foals. RESULTS: Changes in superficial digital flexor CSA in
all regions were larger than those of other structures from 10 months to 15
months. The suspensory ligament CSA was significantly larger than those of other
structures on Day 1 in both the region of suspensory origin (RSO) and region of
suspensory body (RSBO). This condition continued until 2 months in the RSO and
until 5 months in the RSBO. The changes in deep digital flexor CSA were larger
than those of other structures from 2 to 5 months in both the RSO and RSBO.
CONCLUSIONS: The rate of change in each structure varies with age. Thus, the
functional adaptation with age that takes place may differ among structures
because the primary function of each structure differs.
PMID- 25124719
TI - Insights into the influence of dispersion correction in the theoretical treatment
of guanidine-quinoline copper(I) complexes.
AB - For the description of steric effects, dispersion correction is important in
density functional theory. By investigation of sterically encumbered guanidine
quinoline copper bis(chelate) complexes, we could show that the correct
description requires modern dispersion correction using Becke-Johnson (BJ)
damping and that earlier dispersion corrections are not sufficient. The triple
zeta basis set def2-TZVP of the Ahlrichs series is balanced and converged for the
structural description. With regard to functionals, the best structural
description is obtained with the TPSSh functional but B3LYP is very suited as
well. Cutting of ligand substituents leads to distortions which limit the
predictive ability of such calculations. We recommend the calculation of "full"
chemical systems with inclusion of dispersion correction using BJ damping. In the
further analysis of the regarded copper bis(chelate) complexes, we found that the
theoretical description of optical and Raman spectra is not much affected by the
dispersion although charge transfer excitations come into play and that
B3LYP/def2-TZVP is the best choice. Hence, we can derive the result that the
correct structural description with dispersion serves as crucial basis for
subsequent calculation steps.
PMID- 25124720
TI - Combined semilunar valve stenoses in neonates: management approaches and
literature review.
AB - Combination of right and left ventricular outflow tracts obstruction is extremely
rare. Neonates with combined aortic stenosis (AS) and pulmonary stenosis (PS)
present in critical condition and required urgent treatment. The management
approach is not well defined. We report five female neonates with combined AS and
PS presented to our institute in the last 5 years, age (1-18 days), weight (2.2
3.4 kg). Two had associated muscular ventricular septal defects. The mean Doppler
gradient across the aortic valve (AV) was 73 mmHg (53-105 mmHg) and across the
pulmonary valve was 62 mmHg (44-76 mmHg). Three had balloon dilatation and one
surgical repair. The fifth patient was managed conservatively, but had sudden
cardiac death at age of 3 months. One patient arrived in shock and sepsis,
underwent emergency balloon dilation of the AV in the ICU. Despite decreasing the
gradient, she died next day after the procedure. The surviving children were well
at median follow-up age of 3.4 years. This is an extremely rare combination which
needs early intervention. The management approach is not well defined.
Interventional catheterization is possibly the better option.
PMID- 25124718
TI - Proteomic analysis of the Plasmodium male gamete reveals the key role for
glycolysis in flagellar motility.
AB - BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria
transmission. While male gametes are thought to be amongst the simplest
eukaryotic cells and are proven targets of transmission blocking immunity, little
is known about their molecular organization. For example, the pathway of energy
metabolism that power motility, a feature that facilitates gamete encounter and
fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified
and analysed by whole-cell proteomic analysis for the first time. Data are
available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins
were recovered, they included all male gamete proteins described thus far.
Amongst them were the 11 enzymes of the glycolytic pathway. The hexose
transporter was localized to the gamete plasma membrane and it was shown that
microgamete motility can be suppressed effectively by inhibitors of this
transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the
first whole-cell proteomic analysis of the malaria male gamete. It identifies
glycolysis as the likely exclusive source of energy for flagellar beat, and
provides new insights in original features of Plasmodium flagellar organization.
PMID- 25124721
TI - Cumulative radiation exposure in pediatric patients with congenital heart
disease.
AB - Certain pediatric patients undergoing surgery for the most severe forms of
congenital heart disease are exposed to high doses of ionizing radiation. The
amount of cumulative radiation exposure from all modalities has not yet been
evaluated. The purpose of our study was to evaluate the cumulative radiation
exposure in a contemporary cohort of patients with congenital heart disease
undergoing single-ventricle palliation. This is a single-center, retrospective
study of pediatric patients undergoing Fontan completion between May 2005 and May
2010. Radiation exposure from all procedures including cardiac catheterizations,
computed tomography (CT) scans, plain film radiography, and nuclear medicine
scans was evaluated. Radiation dose was calculated as the dose area product (MUGy
m(2)) and was measured in all cardiac catheterizations, CT scans, and other
imaging modalities. Seventy patients who underwent Fontan completion at a mean
age of 3.6 +/- 1.5 years (range 1.4-8 years) were included in the study. Mean
number of chest X-rays was 32 +/- 8 (range 10-285) with a mean cumulative total
exposure of 1,320 MUGy m(2) (range 480-12,960) per patient. Mean number of
cardiac catheterizations was 2.45 +/- 1.3 (range 1-8), and mean fluoroscopy and
cine angiography exposures per case were 1,103 +/- 245 and 1,412 +/- 273 MUGy
m(2) giving a mean cumulative exposure of 9,054 MUGy m(2) (range 2,515-201,200)
per patient for all catheterizations. Mean number of CT scans performed was 0.44
+/- 0.4 (0-11), and the mean exposure was 352 MUGy m(2), giving a mean cumulative
total of 154 MUGy m(2) (range 0-3,872) per person. A total of five lung perfusion
scans were carried out. Radiation exposure in patients with congenital heart
disease undergoing single-ventricle palliation is quite variable. Most of the
exposure to ionizing radiation occurs during cardiac catheterization. Strategies
to utilize other imaging modalities such as MRI would decrease exposure in this
particular group of patients who may be particularly vulnerable to its side
effects.
PMID- 25124722
TI - Synthesis of pyridazinones through the copper(I)-catalyzed multicomponent
reaction of aldehydes, hydrazines, and alkynylesters.
AB - The copper-catalyzed multicomponent cyclization reaction, which combined
aldehydes, hydrazines, and alkynylesters, was applied in the synthesis of
pyridazinones. The reaction was regioselective and gave only six-membered
pyridazinones in the complete absence of five-membered pyrazoles or a
regioisomeric mixture. During this investigation, the use of 2-halobenzaldehyde
as the starting material, under identical reaction conditions, gave 6-(2
ethoxyphenyl)pyridazinones after sequential Michael addition/1,2-addition/Ullmann
cross-coupling reactions.
PMID- 25124723
TI - SLC19A1, SLC46A1 and SLCO1B1 polymorphisms as predictors of methotrexate-related
toxicity in Portuguese rheumatoid arthritis patients.
AB - Methotrexate (MTX) is used for rheumatoid arthritis (RA) treatment showing a wide
toxicity profile. This study aimed to evaluate the influence of single nucleotide
polymorphisms (SNPs) in genes encoding for MTX transporters with the occurrence
of MTX-related toxicity (overall and gastrointestinal). A total of 233 Portuguese
RA patients were genotyped for 23 SNPs. Haplotype analyses were performed and a
toxicogenetic risk index (TRI) was created for SNPs that revealed to be
statistically significant. Regarding MTX overall toxicity, an increased risk was
associated to SLC19A1 rs7499 G carriers (p = 0.017), SLC46A1 rs2239907 GG (p =
0.030) and, SLCO1B1 rs4149056 T carriers (p = 0.040) and TT (p = 0.019). TRI
revealed that patients with Index 3 were 18-fold more likely to present an
adverse drug reaction when compared to those with Index 1 (p = 0.001). For MTX
gastrointestinal toxicity, results demonstrated an increased risk associated with
SLC19A1 rs7499 G carriers (p = 0.012) and GG (p = 0.045), SLC19A1 rs1051266 G
carriers (p = 0.034), SLC19A1 rs2838956 A carriers (p = 0.049) and, SLCO1B1
rs4149056 T carriers (p = 0.042) and TT (p = 0.025). Haplotype analyses showed
association between GGAG haplotype for SLC19A1 rs7499, rs1051266, rs2838956 and
rs3788200 with MTX gastrointestinal toxicity (p = 0.029). TRI revealed that
patients with Index 4 were 9-fold more likely to present a gastrointestinal
disorder when compared to those with Index 1 (p = 0.020). This study demonstrated
that SLC19A1, SLC46A1 and SLCO1B1 genotypes may help to identify patients with
increased risk of MTX-related overall toxicity and that SLC19A1 and SLCO1B1
genotypes, and SLC19A1 haplotypes may help to identify patients with increased
risk of MTX-related gastrointestinal toxicity.
PMID- 25124725
TI - The BSD2 ortholog in Chlamydomonas reinhardtii is a polysome-associated chaperone
that co-migrates on sucrose gradients with the rbcL transcript encoding the
Rubisco large subunit.
AB - The expression of the CO2 -fixation enzyme ribulose-bisphosphate
carboxylase/oxygenase (Rubisco), which is affected by light, involves the
cysteine-rich protein bundle-sheath defective-2 (BSD2) that was originally
identified in maize bundle-sheath cells. We identified the BSD2 ortholog in
Chlamydomonas reinhardtii as a small protein (17 kDa) localized to the
chloroplast. The algal BSD2-ortholog contains four CXXCXGXG DnaJ-like elements,
but lacks the other conserved domains of DnaJ. BSD2 co-migrated with the rbcL
transcript on heavy polysomes, and both BSD2 and rbcL mRNA shifted to the lighter
fractions under oxidizing conditions that repress the translation of the Rubisco
large subunit (RbcL). This profile of co-migration supports the possibility that
BSD2 is required for the de novo synthesis of RbcL. Furthermore, BSD2 co-migrated
with the rbcL transcript in a C. reinhardtii premature-termination mutant that
encodes the first 60 amino acids of RbcL. In both strains, BSD2 shared its
migration profile with the rbcL transcript but not with psbA mRNA. The chaperone
activity of BSD2 was exemplified by its ability to prevent the aggregation of
both citrate synthase (CS) and RbcL in vitro following their chemical
denaturation. This activity did not depend on the presence of the thiol groups on
BSD2. In contrast, the activity of BSD2 in preventing the precipitation of
reduced beta-chains in vitro in the insulin turbidity assay was thiol-dependent.
We conclude that BSD2 combines a chaperone 'holdase' function with the ability to
interact with free thiols, with both activities being required to protect newly
synthesized RbcL chains.
PMID- 25124727
TI - Cavity-induced microstreaming for simultaneous on-chip pumping and size-based
separation of cells and particles.
AB - We present a microfluidic platform for simultaneous on-chip pumping and size
based separation of cells and particles without external fluidic control systems
required for most existing platforms. The device utilizes an array of
acoustically actuated air/liquid interfaces generated using dead-end side
channels termed Lateral Cavity Acoustic Transducers (LCATs). The oscillating
interfaces generate local streaming flow while the angle of the LCATs relative to
the main channel generates a global bulk flow from the inlet to the outlet. The
interaction of these two competing velocity fields (i.e. global bulk velocity vs.
local streaming velocity) is responsible for the observed separation. It is shown
that the separation of 5 MUm and 10 MUm polystyrene beads is dependent on the
ratio of these two competing velocity fields. The experimental and simulation
results suggest that particle trajectories based only on Stokes drag force cannot
fully explain the separation behavior and that the impact of additional forces
due to the oscillating flow field must be considered to determine the trajectory
of the beads and ultimately the separation behavior of the device. To demonstrate
an application of this separation platform with cellular components, smaller red
blood cells (7.5 +/- 0.8 MUm) are separated from larger K562 cells (16.3 +/- 2.0
MUm) with viabilities comparable to those of controls based on a trypan blue
exclusion assay.
PMID- 25124724
TI - Autoantibodies associated with prenatal and childhood exposure to environmental
chemicals in Faroese children.
AB - Methylmercury, polychlorinated biphenyls (PCBs), and perfluorinated compounds
(PFCs) are ubiquitous and persistent environmental chemicals with known or
suspected toxic effects on the nervous system and the immune system. Animal
studies have shown that tissue damage can elicit production of autoantibodies.
However, it is not known if autoantibodies similarly will be generated and
detectable in humans following toxicant exposures. Therefore, we conducted a
pilot study to investigate if autoantibodies specific for neural and non-neural
antigens could be detected in children at age 7 years who have been exposed to
environmental chemicals. Both prenatal and age-7 exposures to mercury, PCBs, and
PFCs were measured in 38 children in the Faroe Islands who were exposed to widely
different levels of these chemicals due to their seafood-based diet.
Concentrations of IgM and IgG autoantibodies specific to both neural
(neurofilaments, cholineacetyltransferase, astrocyte glial fibrillary acidic
protein, and myelin basic protein) and non-neural (actin, desmin, and keratin)
antigens were measured and the associations of these autoantibody concentrations
with chemical exposures were assessed using linear regression. Age-7 blood
mercury concentrations were positively associated with titers of multiple neural-
and non-neural-specific antibodies, mostly of the IgM isotype. Additionally,
prenatal blood-mercury and -PCBs were negatively associated with anti-keratin IgG
and prenatal PFOS was negatively associated with anti-actin IgG. These
exploratory findings demonstrate that autoantibodies can be detected in the
peripheral blood following exposure to environmental chemicals. The unexpected
association of exposures with antibodies specific for non-neural antigens
suggests that these chemicals may have toxicities that have not yet been
recognized.
PMID- 25124726
TI - Molecular characterization of SjBIRP, another apoptosis inhibitor, from
Schistosoma japonicum.
AB - Inhibitor of apoptosis proteins (IAP) play an important role in the regulation of
apoptotic processes and are defined by the presence of baculoviral IAP repeat
(BIR) domains. Here, we characterized a cDNA fragment (SjBIRP) synthesized from
the RNA of Schistosoma japonicum, which was found to contain the BIR domain,
suggesting that it could encode a potential IAP. Real-time PCR analyses indicated
that SjBIRP transcription was detected at several stages of the schistosome's
lifecycle, with increased levels present in schistosomula (7 days). In addition,
the SjBIRP was highly expressed in adult females as compared to adult males. A
functional assay showed that SjBIRP could inhibit caspase3/7 activity in both
HeLa cells and schistosome lysates. Furthermore, SjBIRP expression profiles
varied between different hosts of S. japonicum. Taken together, our preliminary
studies suggest that SjBIRP may play a functional role in the regulation of
apoptosis in schistosomes, and that it could be a potential drug target for
schistosomiasis control.
PMID- 25124728
TI - Modeling large-scale dynamic processes in the cell: polarization, waves, and
division.
AB - The past decade has witnessed significant developments in molecular biology
techniques, fluorescent labeling, and super-resolution microscopy, and together
these advances have vastly increased our quantitative understanding of the cell.
This detailed knowledge has concomitantly opened the door for biophysical
modeling on a cellular scale. There have been comprehensive models produced
describing many processes such as motility, transport, gene regulation, and
chemotaxis. However, in this review we focus on a specific set of phenomena,
namely cell polarization, F-actin waves, and cytokinesis. In each case, we
compare and contrast various published models, highlight the relevant aspects of
the biology, and provide a sense of the direction in which the field is moving.
PMID- 25124729
TI - Quality of measurements of acute surgical and traumatic wounds using a digital
wound-analysing tool.
AB - The aim of this study was to assess the reliability of measurements using a wound
analysing tool and their interpretability. Wound surface areas and tissue types,
such as granulation, slough and necrosis, in twenty digital photographs were
measured using a specific software program. The ratio of these tissue types in a
wound was calculated using a wound profile. We calculated the intraclass
coefficient or kappa for reliability, standard error of measurement (SEM) and
smallest detectable change (SDC). The inter-rater reliability intraclass
correlation coefficient (ICC) was 0.99 for surface area, 0.76 for granulation,
0.67 for slough and 0.22 for necrosis. The profiles gave an overall kappa of
0.16. For test-retest reliability, the ICC was 0.99 for surface area, 0.81 for
granulation, 0.80 for slough and 0.97 for necrosis. The agreement of the applied
profiles in the test-retest was 66% (40-100). SEM and SDC for surface area were
0.10/0.27; for granulation, 6.88/19.08; for slough, 7.17/19.87; and for necrosis,
0.35/0.98, respectively. Measuring wound surface area and tissue types by means
of digital photo analysis is a reliable and applicable method for monitoring
wound healing in acute wounds in daily practice as well as in research.
PMID- 25124730
TI - Hospitalizations and associated costs in a population-based study of children
with Down syndrome born in Florida.
AB - BACKGROUND: Our objective was to examine differences in hospital resource usage
for children with Down syndrome by age and the presence of other birth defects,
particularly severe and nonsevere congenital heart defects (CHDs). METHODS: This
was a retrospective, population-based, statewide study of children with Down
syndrome born 1998 to 2007, identified by the Florida Birth Defects Registry
(FBDR) and linked to hospital discharge records for 1 to 10 years after birth. To
evaluate hospital resource usage, descriptive statistics on number of
hospitalized days and hospital costs were calculated. Results were stratified by
isolated Down syndrome (no other coded major birth defect); presence of severe
and nonsevere CHDs; and presence of major FBDR-eligible birth defects without
CHDs. RESULTS: For 2552 children with Down syndrome, there were 6856 inpatient
admissions, of which 68.9% occurred during the first year of life (infancy). Of
the 2552 children, 31.7% (n = 808) had isolated Down syndrome, 24.0% (n = 612)
had severe CHDs, 36.3% (n = 927) had nonsevere CHDs, and 8.0% (n = 205) had a
major FBDR-eligible birth defect in the absence of CHD. Infants in all three
nonisolated DS groups had significantly higher hospital costs compared with those
with isolated Down syndrome. From infancy through age 4, children with severe
CHDs had the highest inpatient costs compared with children in the other sub
groups. CONCLUSION: Results support findings that for children with Down syndrome
the presence of other anomalies influences hospital use and costs, and children
with severe CHDs have greater hospital resource usage than children with other
CHDs or major birth defects without CHDs.
PMID- 25124732
TI - Identification of loci associated with late-onset psoriasis using dense
genotyping of immune-related regions.
AB - BACKGROUND: Chronic plaque psoriasis can be subdivided into two groups according
to the age of onset: type 1 (early onset, before 40 years) and type 2 (late
onset, at or beyond 40 years). So far, 36 genetic loci have been associated with
early-onset psoriasis in genome-wide association studies of white populations,
while few studies have investigated genetic susceptibility to late-onset
psoriasis. OBJECTIVES: To characterize the genetics underpinning late-onset
psoriasis. METHODS: We genotyped 543 cases of late-onset psoriasis and 4373
healthy controls using the Immunochip array, a dense genotyping chip containing
single-nucleotide polymorphisms previously associated with autoimmune diseases.
Imputation using SNP2HLA and stepwise logistic regression analysis was performed
for markers spanning the human leucocyte antigen gene region. RESULTS: Two loci
(HLA-C and IL12B) previously associated with early-onset psoriasis showed
significant association at a genome-wide threshold in the current study (P < 5 *
10(-8)). Six more loci (TRAF3IP2, IL23R, RNF114, IFIH1, IL23A and HLA-A) showed
study-wide significant association (P < 2.3 * 10(-5); calculated using Genetic
type 1 error calculator). Additionally, we identified an association at IL1R1 on
chromosome 2q13, which is not associated with early-onset disease. CONCLUSIONS:
This is the largest study to date of genetic loci in late-onset psoriasis, and
demonstrates the overlap that exists with early-onset psoriasis. It also suggests
that some loci are associated exclusively with late-onset psoriasis.
PMID- 25124731
TI - Phytolatex synthesized gold nanoparticles as novel agent to enhance sun
protection factor of commercial sunscreens.
AB - OBJECTIVE: To study the potential of phytolatex (latex of Jatropha gossypifolia)
fabricated gold nanoparticles as promising candidate in sunscreen formulations
for enhancement in sun protection factor. METHODS: In this study, plant latex was
used as reducing and capping agent to synthesize gold nanoparticles. Latex
fabricated gold nanoparticles were characterized by different analytical
techniques such as UV-Vis spectroscopy, Fourier transforms infrared spectroscopy,
dynamic light scattering, zeta potential, transmission electron microscopy and X
ray diffraction. Potential of sunscreen preparations containing gold
nanoparticles to protect skin from UV radiation was investigated by in vitro sun
protection factor analysis. Transmission electron microscopy and UV-Vis
spectroscopy techniques were used to get insight into mechanism by which AuNPs
enhance sun protection factor of sunscreen. RESULTS: Monodisperse gold
nanoparticles were synthesized using plant latex without need of hazardous
chemical reducing and capping agents. Gold nanoparticles showed surface plasmon
resonance peak at 550 nm in UV-Vis spectroscopic study. Gold nanoparticles were
spherical and triangular in shape with size range of 30-50 nm. The zeta potential
of gold nanoparticles was found to be -9.39 +/- 0.19 mV. XRD analysis confirmed
face-centred cubic (fcc) structure of gold nanoparticles. Incorporation of latex
synthesized gold nanoparticles (2 and 4 [% w/w]) into commercial sunscreens
increased the sun protection factor from 2.43 +/- 0.74 to 24.11 +/- 0.46% than
sunscreen devoid of gold nanoparticles. From UV-Vis absorption spectroscopy and
TEM analysis, it was observed that gold nanoparticles enhance the sun protection
factor of commercial sunscreens due to reflection and scattering of UV radiation.
CONCLUSION: Phytolatex synthesized gold nanoparticle is novel agent to enhance
sun protection factor of commercial sunscreens. Gold nanoparticles aggregation in
commercial sunscreen was the main factor behind SPF enhancement. This study
showed that gold nanoparticles are potent alternative to traditionally used
hazardous titanium dioxide and zinc oxide nanoparticles in sunscreen.
PMID- 25124733
TI - Influence of repeated infusion of capsaicin-contained red pepper sauce on
esophageal secondary peristalsis in humans.
AB - BACKGROUND: The transient receptor potential vanilloid 1 has been implicated as a
target mediator for heartburn perception and modulation of esophageal secondary
peristalsis. Our aim was to determine the effect of repeated esophageal infusion
of capsaicin-contained red pepper sauce on heartburn perception and secondary
peristalsis in healthy adults. METHODS: Secondary peristalsis was performed with
mid-esophageal injections of air in 15 healthy adults. Two separate protocols
including esophageal infusion with saline and capsaicin-contained red pepper
sauce and 2 consecutive sessions of capsaicin-contained red pepper sauce were
randomly performed. KEY RESULTS: After repeated infusion of capsaicin-contained
red pepper sauce, the threshold volume to activate secondary peristalsis was
significantly increased during slow (p < 0.001) and rapid air injections (p =
0.004). Acute infusion of capsaicin-contained red pepper sauce enhanced heartburn
perception (p < 0.001), but the intensity of heartburn perception was
significantly reduced after repeated capsaicin-contained red pepper sauce
infusion (p = 0.007). Acute infusion of capsaicin-contained red pepper sauce
significantly increased pressure wave amplitudes of distal esophagus during slow
(p = 0.003) and rapid air injections (p = 0.01), but repeated infusion of
capsaicin-contained red pepper sauce significantly decreased pressure wave
amplitude of distal esophagus during slow (p = 0.0005) and rapid air injections
(p = 0.003). CONCLUSIONS & INFERENCES: Repeated esophageal infusion of capsaicin
appears to attenuate heartburn perception and inhibit distension-induced
secondary peristalsis in healthy adults. These results suggest capsaicin
sensitive afferents in modulating sensorimotor function of secondary peristalsis
in human esophagus.
PMID- 25124735
TI - TiO2 hollow spheres composed of highly crystalline nanocrystals exhibit superior
lithium storage properties.
AB - While the synthesis of TiO2 hollow structures is well-established, in most cases
it is particularly difficult to control the crystallization of TiO2 in solution
or by calcination. As a result, TiO2 hollow structures do not really exhibit
enhanced lithium storage properties. Herein, we report a simple and cost
effective template-assisted method to synthesize anatase TiO2 hollow spheres
composed of highly crystalline nanocrystals, in which carbonaceous (C) spheres
are chosen as the removable template. The release of gaseous species from the
combustion of C spheres may inhibit the growth of TiO2 crystallites so that
instead small TiO2 nanocrystals are generated. The small size and high
crystallinity of primary TiO2 nanoparticles and the high structural integrity of
the hollow spheres gives rise to significant improvements in the cycling
stability and rate performance of the TiO2 hollow spheres.
PMID- 25124734
TI - First case of multidrug-resistant blaNDM-1- and blaOXA-232-carrying Klebsiella
pneumoniae and its probable cross-transmission in a French hospital.
PMID- 25124737
TI - More-frequent extreme northward shifts of eastern Indian Ocean tropical
convergence under greenhouse warming.
AB - The Intertropical Convergence Zone (ITCZ) in the tropical eastern Indian Ocean
exhibits strong interannual variability, often co-occurring with positive Indian
Ocean Dipole (pIOD) events. During what we identify as an extreme ITCZ event, a
drastic northward shift of atmospheric convection coincides with an anomalously
strong north-minus-south sea surface temperature (SST) gradient over the eastern
equatorial Indian Ocean. Such shifts lead to severe droughts over the maritime
continent and surrounding islands but also devastating floods in southern parts
of the Indian subcontinent. Understanding future changes of the ITCZ is therefore
of major scientific and socioeconomic interest. Here we find a more-than-doubling
in the frequency of extreme ITCZ events under greenhouse warming, estimated from
climate models participating in the Coupled Model Intercomparison Project phase 5
that are able to simulate such events. The increase is due to a mean state change
with an enhanced north-minus-south SST gradient and a weakened Walker
Circulation, facilitating smaller perturbations to shift the ITCZ northwards.
PMID- 25124736
TI - Epigallocatechin-3-gallate functions as a physiological regulator by modulating
the jasmonic acid pathway.
AB - Flavonoids, a class of plant polyphenols derived from plant secondary metabolism,
play important roles in plant development and have beneficial effects on human
health. Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol, and
its molecular and biochemical mechanism have been followed with interest. The
shared signaling heritage or convergence of organisms has allowed us to extend
this research into the model plant, Arabidopsis thaliana. Here, we showed that
EGCG could promote jasmonic acid (JA) signaling in A. thaliana. EGCG not only
inhibited seed germination but also elevated the resistance to necrotrophic
Botrytis cinerea, partly by altering the relative strength of JA signaling.
Accordingly, JA marker gene induction, seed germination inhibition and the
increased resistance to B. cinerea were attenuated in the JA-insensitive coi1-2
mutant. The coi1-2 mutant was partially insensitive to the treatment of EGCG,
further implicating the function of EGCG in JA signaling and/or perception. Our
results indicate that EGCG, a member of the flavonoid class of polyphenols,
affects signal processing in seed development and disease susceptibility via
modulation of JA signaling.
PMID- 25124738
TI - Neurotoxicology and development: human, environmental and social impacts.
AB - The 12th International symposium of the Scientific Committee on Neurotoxicology
and Psychophysiology, International Commission on Occupational Health was held in
Cape Town, South Africa on March 24-27, 2013. Reflecting the meeting aiming to
build greater focus on challenges facing working populations and communities in
developing countries, the Symposium theme was Neurotoxicology and Development:
Human, Environmental and Social Impacts. A total of 23 countries were represented
with strong participation from 5 African countries. In addition to the more
traditional topics of these Symposia, like metal, solvents and pesticides
neurotoxicity, the conference embraced several new themes including affective
disorders arising from chemical exposure, neurodevelopmental impacts in early
life and novel approaches to genetic and epigenetic biomarkers for the assessment
of neurotoxic impact. The theme of the conference prompted extensive discussions,
which have laid the basis for a number of new directions for research, advocacy
and capacity building to prevent and manage chemical neurotoxicity in workplace
and community settings across the globe.
PMID- 25124739
TI - Prenatal and postnatal lead exposure and cognitive development of infants
followed over the first three years of life: a prospective birth study in the
Pearl River Delta region, China.
AB - PURPOSE: Our pilot studies showed that there was a significant relationship
between low cord blood levels and scores of neonatal behavioral neurological
assessment. The study was further to probe the adverse cognitive effects induced
by low-level lead exposure during prenatal and postnatal period. METHOD: Totally
362 mothers with their infants located the PRD, Guangdong, China participated in
the study during their stay in these center: 141 in the high lead group
[umbilical-cord blood lead levels (UCBLLs)>=3.92MUg/dl] and 102 in the low lead
group (UCBLLs<=1.89MUg/dl). The other 137 subjects failed to complete the study
for a variety of reasons. Blood Lead levels (BLLs) were measured by atomic
absorption spectrophotometry, equipped with a graphite furnace. The developmental
functioning of infants and children was assessed with BSID-II. The children's
birth outcome and the rest of information were obtained from their medical
records or a comprehensive questionnaire from their parents, which contained
demographic characteristics, lifestyle, mother's IQ and environmental lead
sources, etc. RESULTS: Of 380, 243 newborns (63.95%) had complete data collection
for all variables included at 6, 12, 24 and 36 months of age. The mean UCBLLs for
high and low lead group were 5.63+/-0.32MUg/dl and 1.35+/-0.26MUg/dl,
respectively. Significant inverse associations have been found between the UCBLLs
and the MDI and the PDI. The associations might attenuate over subsequent years.
BLLs at 24 months were significantly associated, in an inverse direction, with
MDI at 24 and 36 months. The observed trend of cognitive deficit beginning at 6
months of life might persist, and even develop over the coming years. A positive
significant effect of home nurture environment was observed on MDI scores at 12,
24, 36 months of age and PDI scores at 24 and 36 months of age. CONCLUSION: Our
study demonstrates that prenatal and postnatal lead exposure as low as 5MUg/dl
has an adverse effect on neurodevelopment, best arrested by measuring UCBLLs and
BLLs at 24 months of age, and suggest a reference for a blood lead critical value
below 5MUg/dL. The collective evidence indicate that low lead exposure must be
addressed appropriately by health policy makers and argues for an improvement of
home nurture environment, i.e., reduce the burden of Pb on children and,
strengthen the training of cognitive ability.
PMID- 25124740
TI - Dramatic decrease in fluoroquinolones in the pediatric population in Korea.
AB - PURPOSE: This study was performed to evaluate the change of prescribing patterns
after the regulatory action regarding fluoroquinolones in pediatric patients.
METHODS: We conducted a time series analysis using the Korea Health Insurance
Review and Assessment Service National Patients Sample database. Study subjects
consisted of pediatric patients under 18 years of age who were prescribed
antibiotics at least once (ATC code, J01) before (January 2009-December 2009) and
after implementation (January 2010-December 2011) of the regulation. The use of
fluoroquinolones was defined as the use of the following antibiotics for at least
once in pediatric patients: ofloxacin, ciprofloxacin, norfloxacin, lomefloxacin,
levofloxacin, and gemifloxacin. We calculated the number of pediatric
fluoroquinolone users for each month. The difference between proportions before
and after the regulation was estimated as relative and absolute reduction of
fluoroquinolone use. We calculated 95% confidence intervals (CI). RESULTS: We
identified 4, 945, 169 antibiotic prescriptions in 484, 914 pediatric patients.
During the 12-month period before implementation, percentage of fluoroquinolone
use was 4.81% (95% CI: 4.70-4.91%, N = 8001). We observed a rapid decrease in the
monthly number of fluoroquinolone users in pediatric population after the
implementation of regulatory action. In the year after regulatory action, the
percentage of fluoroquinolone use was only 0.26% (95% CI: 0.24-0.28%, N = 834).
Overall, there was a 94.55% relative reduction (95% CI: 88.02-101.56%) in the use
of fluoroquinolones. CONCLUSION: Korean regulatory actions regarding
fluoroquinolones had an effect of reducing use in pediatric population.
PMID- 25124741
TI - Simultaneous high-resolution detection of multiple transcripts combined with
localization of proteins in whole-mount embryos.
AB - BACKGROUND: Whole-mount in situ hybridization (WISH) is a fundamental tool for
studying the spatio-temporal expression pattern of RNA molecules in intact
embryos and tissues. The available methodologies for detecting mRNAs in embryos
rely on enzymatic activities and chemical reactions that generate diffusible
products, which are not fixed to the detected RNA, thereby reducing the spatial
resolution of the technique. In addition, current WISH techniques are time
consuming and are usually not combined with methods reporting the expression of
protein molecules. RESULTS: The protocol we have developed and present here is
based on the RNAscope technology that is currently employed on formalin-fixed,
paraffin-embedded and frozen tissue sections for research and clinical
applications. By using zebrafish embryos as an example, we provide a robust and
rapid method that allows the simultaneous visualization of multiple transcripts,
demonstrated here for three different RNA molecules. The optimized procedure
allows the preservation of embryo integrity, while exhibiting excellent signal-to
noise ratios. Employing this method thus allows the determination of the spatial
expression pattern and subcellular localization of multiple RNA molecules
relative to each other at high resolution, in the three-dimensional context of
the developing embryo or tissue under investigation. Lastly, we show that this
method preserves the function of fluorescent proteins that are expressed in
specific cells or cellular organelles and conserves antigenicity, allowing
protein detection using antibodies. CONCLUSIONS: By fine-tuning the RNAscope
technology, we have successfully redesigned the protocol to be compatible with
whole-mount embryo samples. Using this robust method for zebrafish and extending
it to other organisms would have a strong impact on research in developmental,
molecular and cell biology. Of similar significance would be the adaptation of
the method to whole-mount clinical samples. Such a protocol would contribute to
biomedical research and clinical diagnostics by providing information regarding
the three-dimensional expression pattern of clinical markers.
PMID- 25124742
TI - Retronasal odor of dried bonito stock induces umami taste and improves the
palatability of saltiness.
AB - A traditional Japanese umami-rich stock, dried bonito stock, was reported to
improve the palatability of a low-salt diet due to its characteristic aroma. Two
pathways are available for the presentation of odors: the orthonasal and
retronasal pathways. Aroma is perceived through the orthonasal pathway. In
contrast, retronasal application of odors is thought to evoke different
sensations from the orthonasal pathway, which is typically perceived as taste and
modifies taste. Therefore, the effect of retronasal odor on salt-reduction might
be different from that of aroma, that is, orthonasal odor. Thus, the effects of
the retronasal odor of dried bonito stock on the enhancement and improvement of
palatability upon salt reduction were examined using sensory evaluation.
Moreover, the contributions to flavor expression and palatability of dried bonito
stock were also investigated. Although the retronasal odor of dried bonito did
not enhance saltiness, it improved the palatability of saltiness. In the presence
of no tastants except 0.68% NaCl, a content 15% less than that of Japanese
traditional soup, the retronasal odor of dried bonito generated umami, enhanced
the suitability for dried bonito stock, and increased palatability. This
indicates that the retronasal odor of dried bonito stock could improve the
palatability of a salt-reduced diet. These findings can be applied to the
development of new seasonings for improving the palatability of salt-reduced
foods.
PMID- 25124744
TI - Isoflurane reduces the ischemia reperfusion injury surge: a longitudinal study
with MRI.
AB - BACKGROUND: Recent studies show neuroprotective benefits of isoflurane (ISO)
administered during cerebral ischemia. However, the available studies evaluated
cerebral injury only at a single time point following the intervention and thus
the longitudinal effect of ISO on ischemic tissues remains to be investigated.
OBJECTIVE: The objective of the present study was to investigate the longitudinal
effect of ISO treatment in counteracting the deleterious effect of ischemia by
evoking the transcription factor, hypoxia inducible factor-1 (HIF-1), and
vascular endothelial growth factor (VEGF). METHODS: Focal cerebral ischemia was
induced in 70 rats by filament medial cerebral artery occlusion (MCAo) method.
MCAo rats were randomly assigned to control (90 min ischemia) and MCAo+ISO (90
min ischemia+2% ISO) groups. Infarct volume, edema, intracerebral hemorrhage
(ICH), and regional cerebral blood flow (rCBF) were measured in eight in vivo
sequential MR imaging sessions for 3 weeks. Western blot analysis and
immunofluorescence were used to determine the expression level of HIF-1alpha (the
regulatable subunit of HIF-1) and VEGF proteins. RESULTS: ISO inhalation during
ischemia significantly decreased the surge of infarct volume, edema, ICH, and
reduced the mortality rate (p<0.01). ISO transiently altered the rCBF,
significantly enhanced the expression of HIF-1alpha and VEGF, and decreased the
immune cell infiltration. Locomotor dysfunction was ameliorated at a
significantly faster pace, and the benefit was seen to persist up to three weeks.
CONCLUSION: Treatment with ISO during ischemia limits the deadly surge in the
dynamics of ischemia reperfusion injury with no observed long-term inverse
effect.
PMID- 25124743
TI - Enhanced neurocognitive functioning and positive temperament in twins discordant
for bipolar disorder.
AB - OBJECTIVE: Based on evidence linking creativity and bipolar disorder, a model has
been proposed whereby factors influencing liability to bipolar disorder confer
certain traits with positive effects on reproductive fitness. The authors tested
this model by examining key traits known to be associated with evolutionary
fitness, namely, temperament and neurocognition, in individuals carrying
liability for bipolar disorder. Schizophrenia probands and their co-twins were
included as psychiatric controls. METHOD: Twin pairs discordant for bipolar
disorder and schizophrenia and control pairs were identified through the Swedish
Twin Registry. The authors administered a neuropsychological test battery and
temperament questionnaires to samples of bipolar probands, bipolar co-twins,
schizophrenia probands, schizophrenia co-twins, and controls. Multivariate mixed
model analyses of variance were conducted to compare groups on temperament and
neurocognitive scores. RESULTS: Bipolar co-twins showed elevated scores on a
"positivity" temperament scale compared with controls and bipolar probands, while
bipolar probands scored higher on a "negativity" scale compared with their co
twins and controls, who did not differ. Additionally, bipolar co-twins showed
superior performance compared with controls on tests of verbal learning and
fluency, while bipolar probands showed performance decrements across all
neurocognitive domains. In contrast, schizophrenia co-twins showed attenuated
impairments in positivity and overall neurocognitive functioning relative to
their ill proband counterparts. CONCLUSIONS: These findings suggest that supra
normal levels of sociability and verbal functioning may be associated with
liability for bipolar disorder. These effects were specific to liability for
bipolar disorder and did not apply to schizophrenia. Such benefits may provide a
partial explanation for the persistence of bipolar illness in the population.
PMID- 25124746
TI - Use of cholesterol-loaded cyclodextrin in donkey semen cryopreservation improves
sperm viability but results in low fertility in mares.
AB - The use of cholesterol-loaded cyclodextrin (CLC) on semen cryopreservation has
been related with better sperm viability in several species; however, the effect
on fertility is not known in donkey semen. Ejaculates (n = 25) from five donkeys
were diluted in S-MEDIUM with 0, 1, 2 or 3 mg of CLC/120 * 10(6) spermatozoa.
Semen was frozen, and thawed samples were evaluated by computer-assisted sperm
analyser system (CASA), supravital test, hyposmotic swelling test and fluorescent
dyes to assess the integrity of sperm membranes. Mares (n = 60) were inseminated
with frozen-thawed semen treated with the doses of 0 or 1 mg CLC. Percentages of
sperm with progressive motility and with functional plasma membrane were greater
(p < 0.05) in the CLC-treated groups than in the control. Percentages of intact
plasma membrane and intact plasma membrane and acrosome detected by fluorescent
dyes were also greater (p < 0.05) in CLC-treated groups. Although no difference
(p > 0.05) in conception rates was detected between groups (control, 3/30, 10%;
CLC-treated, 1/30, 3.3%), fertility was low for artificial insemination programs
in mares. Therefore, we firstly demonstrated that frozen semen treated with CLC
in S-MEDIA extender before freezing improves the in vitro sperm viability, but
semen treated or not with CLC in S-MEDIUM extender results in a very low
conception rate in mares inseminated with thawed donkey semen.
PMID- 25124747
TI - Evaluating disease-modifying agents: a simulation framework for Alzheimer's
disease.
AB - BACKGROUND: Considerable advances have been made in modeling Alzheimer's disease
(AD), with a move towards individual-level rather than cohort models and
simulations that consider multiple dimensions when evaluating disease severity.
However, the possibility that disease-modifying agents (DMAs) may emerge requires
an update of existing modeling frameworks. OBJECTIVES: The aim of this study was
to develop a simulation allowing for economic evaluation of DMAs in AD. METHODS:
The model was developed based on a previously published, well-validated, discrete
event simulation which measures disease severity on the basis of cognition,
behaviour, and function, and captures the interrelated changes in these measures
for individuals. The updated model adds one more domain, patient dependence, in
addition to cognition, behaviour, and function to better characterize disease
severity. Furthermore, the model was modified to have greater flexibility in
assessing the impact of various important assumptions, such as the long-term
effectiveness of DMAs and their impact on survival, on model outcomes. A
validation analysis was performed to examine how well the model predicted change
in disease severity among patients not receiving DMA treatment by comparing model
results to those observed in two recent phase III clinical trials of
bapineuzumab. In addition, various hypothetical scenarios were tested to
demonstrate the improved features of the model. RESULTS: Validation results show
that the model closely predicts the mean changes in disease severity over 18
months. Results from different hypothetical scenarios show that the model allows
for credible assessment of those major uncertainties surrounding the long-term
effectiveness of DMAs, including the potential impact of improved survival with
DMA treatment. They also indicate that varying these assumptions could have a
major impact on the value of DMAs. CONCLUSIONS: The updated economic model has
good predictive power, but validation against longer-term outcomes is still
needed. Our analyses also demonstrate the importance of designing a model with
sufficient flexibility such that the model allows for assessment of the impact of
key sources of uncertainty on the value of DMAs.
PMID- 25124748
TI - Typology of individuals with substance dependence based on a Montreal
longitudinal catchment area study.
AB - This study sought to develop a typology of individuals with substance dependence
(ISD) based on a longitudinal survey (n = 2,434) and 121 ISD. The latter were
divided into three groups: newly abstinent individuals, chronic dependents and
acute dependents. Individuals' typology was developed by cluster analysis. Newly
abstinent individuals had fewer emotional problems and mental disorders in the
previous 12 months. Four classes of ISD were identified, labelled respectively
"chronic multi-substance consumption and mental disorders comorbidities," "multi
substance consumption," "alcohol and marijuana consumption" and "alcohol
consumption only." Strategies adapted to each of these profiles could be promoted
for more effective treatment.
PMID- 25124750
TI - Implementing a medical screening and referral program for rural emergency
departments.
AB - CONTEXT: Emergency Department (ED) overcrowding due to nonemergent use is an
ongoing concern. In 2011, a regional health system that primarily serves rural
communities in Texas instituted a new program to medically screen and refer
nonemergent patients to nearby affiliated rural health clinics (RHCs). PURPOSE:
This formative evaluation describes the program goals, process, and early
implementation experiences at 2 sites that adopted the program before wider
implementation within the rural health system. METHODS: Primary data collection
including document review, internal stakeholder interviews, and direct
observation of program processes were used for this formative evaluation of
program implementation in light of program goals and objectives. Fourteen key
informants were asked questions related to the program concept, structure, and
implementation. RESULTS: The program, as implemented, aligned with initial
program goals, but it was dependent on ED screening staff and RHC availability.
Some adjustments to the program were needed, including RHC hours, consistency
among staff in making referrals, patient education, and improving patient uptake
on the referral. Stakeholders reported lessons learned related to training, staff
buy-in, Emergency Medical Treatment and Labor Act (EMTALA), and
intraorganizational cooperation. DISCUSSION: The system was able to leverage
excess capacity of affiliated RHCs to accommodate low-acuity patients referred
from the ED and may lead to improvements in Triple Aim goals of increased patient
satisfaction, better population health and outcomes, and lower per capita costs.
Lessons learned from this program may inform similar processes aimed to reduce
nonemergency ED utilization by other rural health systems.
PMID- 25124749
TI - Complement factor C5a induces atherosclerotic plaque disruptions.
AB - Complement factor C5a and its receptor C5aR are expressed in vulnerable
atherosclerotic plaques; however, a causal relation between C5a and plaque
rupture has not been established yet. Accelerated atherosclerosis was induced by
placing vein grafts in male apoE(-/-) mice. After 24 days, when advanced plaques
had developed, C5a or PBS was applied locally at the lesion site in a pluronic
gel. Three days later mice were killed to examine the acute effect of C5a on late
stage atherosclerosis. A significant increase in C5aR in the plaque was
detectable in mice treated with C5a. Lesion size and plaque morphology did not
differ between treatment groups, but interestingly, local treatment with C5a
resulted in a striking increase in the amount of plaque disruptions with
concomitant intraplaque haemorrhage. To identify the potential underlying
mechanisms, smooth muscle cells and endothelial cells were treated in vitro with
C5a. Both cell types revealed a marked increase in apoptosis after stimulation
with C5a, which may contribute to lesion instability in vivo. Indeed, apoptosis
within the plaque was seen to be significantly increased after C5a treatment. We
here demonstrate a causal role for C5a in atherosclerotic plaque disruptions,
probably by inducing apoptosis. Therefore, intervention in complement factor C5a
signalling may be a promising target in the prevention of acute atherosclerotic
complications.
PMID- 25124752
TI - Impulsive exponential synchronization of randomly coupled neural networks with
Markovian jumping and mixed model-dependent time delays.
AB - In this paper, the exponential synchronization problem for an array of N randomly
coupled neural networks with Markovian jump and mixed model-dependent time delays
via impulsive control is investigated. The jump parameters are determined by a
continuous-time, discrete-state Markovian chain, and the mixed time delays under
consideration comprise both discrete and continuous distributed delays. By making
use of the Kronecker product and some useful techniques, a novel Lyapunov
Krasovskii functional suitable for handling distributed delays was proposed and
then we show that the addressed synchronization problem is solvable if a set of
linear matrix inequalities (LMIs) are feasible. The results presented in this
paper generalize and improve many known results. Two numerical examples are also
given to show the effectiveness of the theoretical results.
PMID- 25124753
TI - Global exponential almost periodicity of a delayed memristor-based neural
networks.
AB - In this paper, the existence, uniqueness and stability of almost periodic
solution for a class of delayed memristor-based neural networks are studied. By
using a new Lyapunov function method, the neural network that has a unique almost
periodic solution, which is globally exponentially stable is proved. Moreover,
the obtained conclusion on the almost periodic solution is applied to prove the
existence and stability of periodic solution (or equilibrium point) for delayed
memristor-based neural networks with periodic coefficients (or constant
coefficients). The obtained results are helpful to design the global exponential
stability of almost periodic oscillatory memristor-based neural networks. Three
numerical examples and simulations are also given to show the feasibility of our
results.
PMID- 25124751
TI - Isotopic ratio based source apportionment of children's blood lead around coking
plant area.
AB - Lead exposure in the environment is a major hazard affecting human health,
particularly for children. The blood lead levels in the local children living
around the largest coking area in China were measured, and the source of blood
lead and the main pathways of lead exposure were investigated based on lead
isotopic ratios ((207)Pb/(206)Pb and (208)Pb/(206)Pb) in blood and in a variety
of media, including food, airborne particulate matter, soil, dust and drinking
water. The children's blood lead level was 5.25 (1.59 to 34.36 as range) MUg dL(
1), lower than the threshold in the current criteria of China defined by the US
Centers for Disease Control (10 MUg dL(-1)). The isotopic ratios in the blood
were 2.111+/-0.018 for (208)Pb/(206)Pb and 0.864+/-0.005 for (207)Pb/(206)Pb,
similar to those of vegetables, wheat, drinking water, airborne particulate
matter, but different from those of vehicle emission and soil/dust, suggesting
that the formers were the main pathway of lead exposure among the children. The
exposure pathway analysis based on the isotopic ratios and the human health risk
assessment showed that dietary intake of food and drinking water contributed
93.67% of total exposed lead. The study further indicated that the coal used in
the coking plant is the dominant pollution source of lead in children's blood.
PMID- 25124745
TI - Vector platforms for gene therapy of inherited retinopathies.
AB - Inherited retinopathies (IR) are common untreatable blinding conditions. Most of
them are inherited as monogenic disorders, due to mutations in genes expressed in
retinal photoreceptors (PR) and in retinal pigment epithelium (RPE). The retina's
compatibility with gene transfer has made transduction of different retinal cell
layers in small and large animal models via viral and non-viral vectors possible.
The ongoing identification of novel viruses as well as modifications of existing
ones based either on rational design or directed evolution have generated vector
variants with improved transduction properties. Dozens of promising proofs of
concept have been obtained in IR animal models with both viral and non-viral
vectors, and some of them have been relayed to clinical trials. To date,
recombinant vectors based on the adeno-associated virus (AAV) represent the most
promising tool for retinal gene therapy, given their ability to efficiently
deliver therapeutic genes to both PR and RPE and their excellent safety and
efficacy profiles in humans. However, AAVs' limited cargo capacity has prevented
application of the viral vector to treatments requiring transfer of genes with a
coding sequence larger than 5 kb. Vectors with larger capacity, i.e.
nanoparticles, adenoviral and lentiviral vectors are being exploited for gene
transfer to the retina in animal models and, more recently, in humans. This
review focuses on the available platforms for retinal gene therapy to fight
inherited blindness, highlights their main strengths and examines the efforts to
overcome some of their limitations.
PMID- 25124756
TI - Early embryonic specification of vertebrate cranial placodes.
AB - Cranial placodes contribute to many sensory organs and ganglia of the vertebrate
head. The olfactory, otic, and lateral line placodes form the sensory receptor
cells and neurons of the nose, ear, and lateral line system; the lens placode
develops into the lens of the eye; epibranchial, profundal, and trigeminal
placodes contribute sensory neurons to cranial nerve ganglia; and the
adenohypophyseal placode gives rise to the anterior pituitary, a major endocrine
control organ. Despite these differences in fate, all placodes are now known to
originate from a common precursor, the preplacodal ectoderm (PPE). The latter is
a horseshoe-shaped domain of ectoderm surrounding the anterior neural plate and
neural crest and is defined by expression of transcription factor Six1, its
cofactor Eya1, and other members of the Six and Eya families. Studies in
zebrafish, Xenopus, and chick reveal that the PPE is specified together with
other ectodermal territories (epidermis, neural crest, and neural plate) during
early embryogenesis. During gastrulation, domains of ventrally (e.g., Dlx3/Dlx5,
GATA2/GATA3, AP2, Msx1, FoxI1, and Vent1/Vent2) and dorsally (e.g., Zic1, Sox3,
and Geminin) restricted transcription factors are established in response to a
gradient of BMP and help to define non-neural and neural competence territories,
respectively. At neural plate stages, the PPE is then induced in the non-neural
competence territory by signals from the adjacent neural plate and mesoderm
including FGF, BMP inhibitors, and Wnt inhibitors. Subsequently, signals from
more localized signaling centers induce restricted expression domains of various
transcription factors within the PPE, which specify multiplacodal areas and
ultimately individual placodes. For further resources related to this article,
please visit the WIREs website. CONFLICT OF INTEREST: The author has declared no
conflicts of interest for this article.
PMID- 25124757
TI - Cell-intrinsic timing in animal development.
AB - In certain instances we can witness cells controlling the sequence of their
behaviors as they divide and differentiate. Striking examples occur in the
nervous systems of animals where the order of differentiated cell types can be
traced to internal changes in their progenitors. Elucidating the molecular
mechanisms underlying such cell fate succession has been of interest for its role
in generating cell type diversity and proper tissue structure. Another well
studied instance of developmental timing occurs in the larva of the nematode
Caenorhabditis elegans, where the heterochronic gene pathway controls the
succession of a variety of developmental events. In each case, the identification
of molecules involved and the elucidation of their regulatory relationships is
ongoing, but some important factors and dynamics have been revealed. In
particular, certain homologs of worm heterochronic factors have been shown to
work in neural development, alerting us to possible connections among these
systems and the possibility of universal components of timing mechanisms. These
connections also cause us to consider whether cell-intrinsic timing is more
widespread, regardless of whether multiple differentiated cell types are produced
in any particular order. For further resources related to this article, please
visit the WIREs website. CONFLICT OF INTEREST: The authors have declared no
conflicts of interest for this article.
PMID- 25124759
TI - Arterial tortuosity in patients with Filamin A- associated vascular aneurysms.
PMID- 25124755
TI - Developmental programs of lung epithelial progenitors: a balanced progenitor
model.
AB - The daunting task of lung epithelium development is to transform a cluster of
foregut progenitors into a three-dimensional (3D) tubular network with distinct
cell types distributed at their appropriate locations. A complete understanding
of lung development needs to address not only how, but also where, different cell
types form. We propose that the lung epithelium forms through regulated
deployment of three developmental programs: branching morphogenesis to expand
progenitors and build a tree-like tubular network, airway differentiation to
specify cells for the proximal conducting airways, and alveolar differentiation
to specify cells for the peripheral gas exchange region. Each developmental
program has its unique morphological features and molecular control mechanisms;
their spatiotemporal coordination can be accounted for in a balanced progenitor
model where progenitors balance between alternative developmental programs in
response to spatiotemporal cues. This model integrates progenitor morphogenesis
and differentiation, and provides new insights to lung immaturity in preterm
birth and lung evolution. Advanced gene targeting and 3D imaging tools are needed
to achieve a comprehensive understanding of lung epithelial progenitors on
molecular, cellular, and morphological levels. For further resources related to
this article, please visit the WIREs website. CONFLICT OF INTEREST: The authors
have declared no conflicts of interest for this article.
PMID- 25124761
TI - The movement of the non-cell-autonomous transcription factor, SHORT-ROOT relies
on the endomembrane system.
AB - Plant cells are able to convey positional and developmental information between
cells through the direct transfer of transcription factors. One well studied
example of this is the SHORT-ROOT (SHR) protein, which moves from the stele into
the neighboring ground tissue layer to specify endodermis. While it has been
shown that SHR trafficking relies on plasmodesmata (PD), and interaction with the
SHR INTERACTING EMBRYONIC LETHAL (SIEL) protein, little information is known
about how SHR trafficking is controlled or how SIEL promotes the movement of SHR.
Here we show that SHR can move from multiple different cell types in the root.
Analysis of subcellular localization indicates that in the cytoplasm of root or
leaf cells, SHR localizes to endosomes in a SIEL-dependent manner. Interference
of early and late endosomes disrupts intercellular movement of SHR. Our findings
reveal an essential role for the plant endomembrane, independent of secretion, in
the intercellular trafficking of SHR.
PMID- 25124754
TI - Maternal control of the Drosophila dorsal-ventral body axis.
AB - The pathway that generates the dorsal-ventral (DV) axis of the Drosophila embryo
has been the subject of intense investigation over the previous three decades.
The initial asymmetric signal originates during oogenesis by the movement of the
oocyte nucleus to an anterior corner of the oocyte, which establishes DV polarity
within the follicle through signaling between Gurken, the Drosophila Transforming
Growth Factor (TGF)-alpha homologue secreted from the oocyte, and the Drosophila
Epidermal Growth Factor Receptor (EGFR) that is expressed by the follicular
epithelium cells that envelop the oocyte. Follicle cells that are not exposed to
Gurken follow a ventral fate and express Pipe, a sulfotransferase that
enzymatically modifies components of the inner vitelline membrane layer of the
eggshell, thereby transferring DV spatial information from the follicle to the
egg. These ventrally sulfated eggshell proteins comprise a localized cue that
directs the ventrally restricted formation of the active Spatzle ligand within
the perivitelline space between the eggshell and the embryonic membrane. Spatzle
activates Toll, a transmembrane receptor in the embryonic membrane. Transmission
of the Toll signal into the embryo leads to the formation of a ventral-to-dorsal
gradient of the transcription factor Dorsal within the nuclei of the syncytial
blastoderm stage embryo. Dorsal controls the spatially specific expression of a
large constellation of zygotic target genes, the Dorsal gene regulatory network,
along the embryonic DV circumference. This article reviews classic studies and
integrates them with the details of more recent work that has advanced our
understanding of the complex pathway that establishes Drosophila embryo DV
polarity. For further resources related to this article, please visit the WIREs
website. CONFLICT OF INTEREST: The authors have declared no conflicts of interest
for this article.
PMID- 25124760
TI - Structural insights for HIV-1 therapeutic strategies targeting Vif.
AB - HIV-1 viral infectivity factor (Vif) is a viral accessory protein that is
required for HIV-1 infection due largely to its role in recruiting antiretroviral
factors of the APOBEC3 (apolipoprotein B editing catalytic subunit-like 3) family
to an E3 ubiquitin ligase complex for polyubiquitylation and proteasomal
degradation. The crystal structure of the (near) full-length Vif protein in
complex with Elongin (Elo)B/C, core-binding factor (CBF)beta and Cullin (Cul)5
revealed that Vif has a novel structural fold. In our opinion the structural data
revealed not only the protein-protein interaction sites that determine Vif
stability and interaction with cellular proteins, but also motifs driving Vif
homodimerization, which are essential in Vif functionality and HIV-1 infection.
Vif-mediated protein-protein interactions are excellent targets for a new class
of antiretroviral therapeutics to combat AIDS.
PMID- 25124762
TI - A mathematical model of the human metabolic system and metabolic flexibility.
AB - In healthy subjects some tissues in the human body display metabolic flexibility,
by this we mean the ability for the tissue to switch its fuel source between
predominantly carbohydrates in the postprandial state and predominantly fats in
the fasted state. Many of the pathways involved with human metabolism are
controlled by insulin and insulin-resistant states such as obesity and type-2
diabetes are characterised by a loss or impairment of metabolic flexibility. In
this paper we derive a system of 12 first-order coupled differential equations
that describe the transport between and storage in different tissues of the human
body. We find steady state solutions to these equations and use these results to
nondimensionalise the model. We then solve the model numerically to simulate a
healthy balanced meal and a high fat meal and we discuss and compare these
results. Our numerical results show good agreement with experimental data where
we have data available to us and the results show behaviour that agrees with
intuition where we currently have no data with which to compare.
PMID- 25124763
TI - Modelling the impact of marine reserves on a population with depensatory
dynamics.
AB - In this study, we use a spatially implicit, stage-structured model to evaluate
marine reserve effectiveness for a fish population exhibiting depensatory (strong
Allee) effects in its dynamics. We examine the stability and sensitivity of the
equilibria of the modelled system with regards to key system parameters and find
that for a reasonable set of parameters, populations can be protected from a
collapse if a small percentage of the total area is set aside in reserves.
Furthermore, the overall abundance of the population is predicted to achieve a
maximum at a certain ratio A of reserve area to fished area, which depends
heavily on the other system parameters such as the net export rate of fish from
the marine reserves to the fished areas. This finding runs contrary to the
contested "equivalence at best" result when comparing fishery management through
traditional catch or effort control and management through marine reserves.
Lastly, we analyse the problem from a bioeconomics perspective by computing the
optimal harvesting policy using Pontryagin's Maximum Principle, which suggests
that the value for A which maximizes the optimal equilibrium fishery yield also
maximizes population abundance when the cost per unit harvest is constant, but
can increase substantially when the cost per unit harvest increases with the area
being harvested.
PMID- 25124764
TI - Age trajectories of mortality from all diseases in the six most populated
countries of the South America during the last decades.
AB - Age trajectories of total mortality represent an irreplaceable source of
information about aging. In principle, age affects mortality from all diseases
differently than it affects mortality from external causes. External causes
(accidents) are excluded here from all causes, and the resultant category "all
diseases" is tested as a helpful tool to better understand the relationship
between mortality and age. Age trajectories of all-diseases mortality are studied
in the six most populated countries of the South America during 1996-2010. The
numbers of deaths for specific causes of death are extracted from the database of
WHO, where the ICD-10 revision is used. The all-diseases mortality shows a strong
minimum, which is hidden in total mortality. Two simple deterministic models fit
the age trajectories of all-diseases mortality. The inverse proportion between
mortality and age fits the mortality decreases up to minimum value in all six
countries. All previous models describing mortality decline after birth are
discussed. Theoretical relationships are derived between the parameter in the
first model and standard mortality indicators: Infant mortality, Neonatal
mortality, and Postneonatal mortality. The Gompertz model extended with a small
positive quadratic element fit the age trajectories of all-diseases mortality
after the age of 10 years.
PMID- 25124765
TI - Dynamics of a producer-grazer model incorporating the effects of excess food
nutrient content on grazer's growth.
AB - Modeling under the framework of ecological stoichiometric allows the
investigation of the effects of food quality on food web population dynamics.
Recent discoveries in ecological stoichiometry suggest that grazer dynamics are
affected by insufficient food nutrient content (low phosphorus (P)/carbon (C)
ratio) as well as excess food nutrient content (high P:C). This phenomenon is
known as the "stoichiometric knife edge." While previous models have captured
this phenomenon, they do not explicitly track P in the producer or in the media
that supports the producer, which brings questions to the validity of their
predictions. Here, we extend a Lotka-Volterra-type stoichiometric model by
mechanistically deriving and tracking P in the producer and free P in the
environment in order to investigate the growth response of Daphnia to algae of
varying P:C ratios. Bifurcation analysis and numerical simulations of the full
model, that explicitly tracks phosphorus, lead to quantitative different
predictions than previous models that neglect to track free nutrients. The full
model shows that the fate of the grazer population can be very sensitive to
excess nutrient concentrations. Dynamical free nutrient pool seems to induce
extreme grazer population density changes when total nutrient is in an
intermediate range.
PMID- 25124766
TI - Ecohydrology of agroecosystems: quantitative approaches towards sustainable
irrigation.
AB - Irrigation represents one of the main strategies to enhance and stabilize
agricultural productivity, by mitigating the effects of rainfall vagaries. In the
face of the projected growth in population and in biofuel demands, as well as
shifts in climate and dietary habits, a more sustainable management of water
resources in agroecosystems is needed. The field of ecohydrology, traditionally
focusing on natural ecosystems, has the potential to offer the necessary
quantitative tools to assess and compare agricultural enterprises across
climates, soil types, crops, and irrigation strategies, accounting for the
unpredictability of the hydro-climatic forcing. Here, agricultural sustainability
and productivity are assessed with reference to water productivity (defined as
the ratio between yield and total supplied water), yields, water requirements,
and their variability-a crucial element for food security and resource allocation
planning. These synthetic indicators are quantified by means of a probabilistic
description of the soil water balance and crop development. The model results
allow the interpretation of patterns of water productivity observed in Zea mays
(maize) and Triticum aestivum (wheat), grown under a variety of soils, climates,
and irrigation strategies. Employing the same modeling framework, the impact of
rainfall pattern and irrigation strategy on yield and water requirements is
further explored. The obtained standard deviations of yield and water
requirements suggest the existence of a nonlinear tradeoff between yield
stabilization and variability of water requirements, which in turn is strongly
impacted by irrigation strategy. Moreover, intermediate rainfall amounts are
associated to the highest variability in yields and irrigation requirements,
although allowing the maximum water productivity. The existence of these
tradeoffs between productivity, reliability, and sustainability poses a problem
for water management, in particular in mesic climates.
PMID- 25124767
TI - When learners surpass their models: mathematical modeling of learning from an
inconsistent source.
AB - It has been reported in the literature that both adults and children can, to a
different degree, modify and regularize the often-inconsistent linguistic input
they receive. We present a new algorithm to model and investigate the learning
process of a learner mastering a set of (grammatical or lexical) forms from an
inconsistent source. The algorithm is related to reinforcement learning and drift
diffusion models of decision making, and possesses several psychologically
relevant properties such as fidelity, robustness, discounting, and computational
simplicity. It demonstrates how a learner can successfully learn from or even
surpass its imperfect source. We use the data collected by Singleton and Newport
(Cognit Psychol 49(4):370-407, 2004) on the performance of a 7-year-boy Simon,
who mastered the American Sign Language (ASL) by learning it from his parents,
both of whom were imperfect speakers of ASL. We show that the algorithm possesses
a frequency boosting property, whereby the frequency of the most common form of
the source is increased by the learner. We also explain several key features of
Simon's ASL.
PMID- 25124768
TI - Serum LDL cholesterol levels and new onset of arterial hypertension: an 8-year
follow-up.
AB - BACKGROUND: Serum cholesterol has been demonstrated to correlate with blood
pressure values; therefore, abnormal levels of serum cholesterol might contribute
to the development of hypertension. The aim of this study was to assess the new
onset of hypertension over a period of 8 years in a pharmacologically untreated
population sample in normo- and hypercholesterolemic individuals. DESIGN: 1864
Caucasian subjects with baseline blood pressure values <140/90 mmHg were
subdivided into two different groups, according to LDL cholesterol changes
observed over a period of 8 years. Group 1 included subjects whose LDL
cholesterol levels remained or decreased within the normal range, while Group 2
included those whose LDL cholesterol levels were persistently increased above the
normal range. The 8-year incidence of new-onset hypertension was 7.1% in Group 1
and 13.8% in Group 2 (P = 0.02), after adjustment for the main confounding risk
factors. The difference between Groups 1 and 2 was confirmed in men (8.2 vs.
13.1%, P = 0.04) and women (6.1. vs. 14.5%, P = 006), as well as in subjects
younger than 65 years (5.7 vs. 10.9%; P = 0.011), but not in older ones.
CONCLUSIONS: Baseline serum LDL cholesterol levels are related to the rate of new
onset hypertension in patients with normal or marginally elevated blood pressure
values.
PMID- 25124769
TI - Cervical internal carotid artery pseudoaneurysm complicating malignant otitis
externa: first case report.
AB - Pseudoaneurysm of the internal carotid artery (ICA) is a rare complication of
head and neck infections. To date, three cases of petrous ICA pseudoaneurysm have
been described as a complication of otogenic infection, including only one
secondary to malignant otitis externa. We present here the first case of cervical
ICA pseudoaneurysm as a complication of malignant otitis externa, and stress the
importance of timely diagnosis to avoid fatal outcomes.
PMID- 25124771
TI - Are 20 human papillomavirus types causing cervical cancer?
AB - In 2012, the International Agency for Research on Cancer concluded that there was
consistent and sufficient epidemiological, experimental and mechanistic evidence
of carcinogenicity to humans for 12 HPV types (HPV16, HPV18, HPV31, HPV33, HPV35,
HPV39, HPV45, HPV51, HPV52, HPV56, HPV58 and HPV59) for cervical cancer.
Therefore, these types were considered as 1A carcinogens. They all belong to the
family of the alpha-Papillomaviridae, in particular to the species alpha5
(HPV51), alpha6 (HPV56), alpha7 (HPV18, HPV39, HPV45, HPV59) and alpha9 (HPV16,
HPV31, HPV33, HPV35, HPV52, HPV58). Less evidence is available for a thirteenth
type (HPV68, alpha7), which is classified as a 2A carcinogen (probably
carcinogenic). Moreover, seven other phylogenetically related types (HPV26,
HPV53, HPV66, HPV67, HPV68, HPV70 and HPV73) were identified as single HPV
infections in certain rare cases of cervical cancer and were considered possibly
carcinogenic (2B carcinogens). Recently, Halec et al [7] demonstrated that the
molecular signature of HPV-induced carcinogenesis (presence of type-specific
spliced E6*| mRNA; increased expression of p16; and decreased expression of
cyclin D1, p53 and Rb) was similar in cervical cancers containing single
infections with one of the eight afore-mentioned 2A or 2B carcinogens to those in
cancers with single infections with group 1 carcinogens. Ninety six percent of
cervical cancers are attributable to one of the 13 most common HPV types (groups
1 and 2A). Including the additional seven HPV types (group 2B) added 2.6%, to
reach a total of 98.7% of all HPV-positive cervical cancers. From recently
updated meta-analyses, it was shown that HPV68, HPV26, HPV66, HPV67, HPV73 and
HPV82 were significantly more common in cancer cases than in women with normal
cervical cytology, suggesting that for these HPV types, an upgrading of the
carcinogen classification could be considered. However, there is no need to
include them in HPV screening tests or vaccines, given their rarity in cervical
cancers.
PMID- 25124770
TI - Differential expression of Toll-like receptors and inflammatory cytokines in
ovine interdigital dermatitis and footrot.
AB - Footrot is a common inflammatory bacterial disease affecting the health and
welfare of sheep worldwide. The pathogenesis of footrot is complex and
multifactorial. The primary causal pathogen is the anaerobic bacterium
Dichelobacter nodosus, with Fusobacterium necrophorum also shown to play a key
role in disease. Since immune-mediated pathology is implicated, the aim of this
research was to investigate the role of the host response in interdigital
dermatitis (ID) and footrot. We compared the expression of Toll-like receptors
(TLRs) and pro-inflammatory cytokines and the histological appearance of
clinically normal in comparison to ID and footrot affected tissues. Severe ID and
footrot were characterised by significantly increased transcript levels of pro
inflammatory cytokines TNFalpha and IL1beta and the pattern recognition receptors
TLR2 and TLR4 in the interdigital skin. This was reflected in the
histopathological appearance, with ID and footrot presenting progressive chronic
active pododermatitis with a mixed lymphocytic and neutrophilic infiltration,
gradually increasing from a mild form in clinically normal feet, to moderate in
ID and to a focally severe form with frequent areas of purulence in footrot.
Stimulation with F. necrophorum and/or D. nodosus extracts demonstrated that
dermal fibroblasts, the resident cell type of the dermis, also contribute to the
inflammatory response to footrot bacteria by increased expression of TNFalpha,
IL1beta and TLR2. Overall, ID and footrot lead to a local inflammatory response
given that expression levels of TLRs and IL1beta were dependent on the disease
state of the foot not the animal.
PMID- 25124772
TI - Different distributions of preproMCH and hypocretin/orexin in the forebrain of
the pig (Sus scrofa domesticus).
AB - Neurons producing melanin-concentrating hormone (MCH) or hypocretin/orexin (Hcrt)
have been implicated in the sleep/wake cycle and feeding behavior. Sleep and
feeding habits vary greatly among mammalian species, depending in part of the
prey/predatory status of animals. However, the distribution of both peptides has
been described in only a limited number of species. In this work, we describe the
distribution of MCH neurons in the brain of the domestic pig. Using in situ
hybridization and immunohistochemistry, their cell bodies are shown to be located
in the posterior lateral hypothalamic area (LHA), as expected. They form a dense
cluster ventro-lateral to the fornix while only scattered cells are present
dorsal to this tract. By comparison, Hcrt cell bodies are located mainly dorsal
to the fornix. Therefore, the two populations of neurons display complementary
distributions in the posterior LHA. MCH projections are, as indicated by MCH
positive axons, very abundant in all cortical fields ventral to the rhinal
sulcus, as well as in the lateral, basolateral and basomedial amygdala. In
contrast, most of the isocortex is sparsely innervated. To conclude, the
distribution of MCH cell bodies and projections shows some very specific features
in the pig brain, that are clearly different of that described in the rat, mouse
or human. In contrast, the Hcrt pattern seems more similar to that in these
species, i.e. more conserved. These results suggest that the LHA anatomic
organization shows some very significant interspecies differences, which may be
related to the different behavioral repertoires of animals with regard to feeding
and sleep/wake cycles.
PMID- 25124773
TI - Radiographic analysis of the restoration of hip joint center following open
reduction and internal fixation of acetabular fractures: a retrospective cohort
study.
AB - BACKGROUND: Unfavorable reduction is considered one of the key factors leading to
joint degeneration and compromised clinical outcome in acetabular fracture
patients. Besides the columns, walls, and superior dome, the postoperative
position of hip joint center (HJC), which is reported to affect hip biomechanics,
should be considered during the assessment of quality of reduction. We aimed to
evaluate the radiographic restoration of HJC in acetabular fractures treated with
open reduction and internal fixation. METHODS: Patients with a displaced
acetabular fracture that received open reduction and internal fixation in the
authors' institution during the past five years were identified from the trauma
database. The horizontal and vertical shifts of HJC were measured in the standard
anteroposterior view radiographs taken postoperatively. The radiographic quality
of fracture reduction was graded according to Matta's criteria. The relationships
between the shift of HJC and the other variables were evaluated. RESULTS: Totally
127 patients with 56 elementary and 71 associated-type acetabular fractures were
included, wherein the majority showed a medial (89.0%) and proximal (93.7%) shift
of HJC postoperatively. An average of 2.8 mm horizontal and 2.2 mm vertical shift
of HJC were observed, which correlated significantly with the quality of fracture
reduction (P < 0.001 for both). The horizontal shift of HJC correlated with the
fracture type (P = 0.022). CONCLUSIONS: The restoration of HJC correlates with
the quality of reduction in acetabular fractures following open reduction and
internal fixation. Further studies are required to address the effects of HJC
shift on the biomechanical changes and clinical outcomes of hip joint, especially
in poorly reduced acetabular fractures.
PMID- 25124776
TI - The neural correlates of cognitive behavioral therapy: recent progress in the
investigation of patients with panic disorder.
AB - Cognitive behavioral therapy (CBT) is an evidence-based treatment for mental
disorders. Several meta-analytical reviews supported its efficacy and
effectiveness in the treatment of panic disorder with agoraphobia (PD/AG).
Recently, it has been shown that neurobiological changes are associated with the
process and outcome of CBT. However, the general and specific neurobiological
effects of CBT are still widely unknown. Therefore, the potential of applying
neuroscience to clinical practice and optimizing CBT is still limited. The
current review summarizes recent findings about the neural correlates of CBT in
PD/AG measured with fMRI. Furthermore, the current review will focus on neural
activation patterns predicting and moderating therapeutic success of CBT, due to
its potential application in personalized treatment in the future. Finally, we
will discuss some future perspectives of the neurosciences in CBT research.
PMID- 25124777
TI - Novel insights related to CF neutrophils.
PMID- 25124778
TI - Oral therapy for multiple myeloma: ixazomib arriving soon.
PMID- 25124780
TI - Old and new news in CLL: "It's the pathway, stupid!".
PMID- 25124779
TI - First do no harm: infectious deaths in pediatric ALL.
PMID- 25124781
TI - A common progenitor cell in LCH and ECD.
PMID- 25124782
TI - Is JAK2V617F finally off the hook?
PMID- 25124783
TI - A step forward back to (induced) fetal.
PMID- 25124784
TI - Less (bacterial diversity) is more (deaths).
PMID- 25124786
TI - Activation of TRKB receptor in murine hematopoietic stem/progenitor cells induced
mastocytosis.
PMID- 25124785
TI - Blood collection methods affect cellular protein integrity: implications for
clinical trial biomarkers and ZAP-70 in CLL.
PMID- 25124787
TI - Engraftment of donor cells with germ-line integration of HHV6 mimics HHV6
reactivation following cord blood/haplo transplantation.
PMID- 25124788
TI - Inhibition of neutrophil-dependent cytotoxicity for human endothelial cells by
ACE inhibitors.
AB - Angiotensin-converting enzyme inhibitors (ACEi) have immunomodulating properties
and have been suggested to protect against endothelial injury, for example
myocardial infarction and reperfusion injury. We tested whether two ACEi
(captopril and enalapril), differing in a thiol group, protected human umbilical
vein endothelial cells (HUVEC) from cytotoxicity induced by polymorphonuclear
neutrophils (PMN) in vitro, when cells were activated by tumour necrosis factor
alpha (TNFalpha) or the arachidonate derivative lipoxin-A4 (LXA4 ), using
separate cytotoxicity pathways. When (51) Cr labelled HUVEC were treated with
captopril (0-500 MUm) or enalapril (0-100 MUm) for 2 h and then activated by
TNFalpha (100 ng/ml) for 24 h, a significant, dose-dependent reduction of (51) Cr
release was observed. Similarly, captopril reduced (51) Cr release when LXA4 (0.1
MUm) was used to stimulate PMN for 4 h. Among previously defined mechanisms of
significance for the cytotoxic reaction, expression of ICAM-1, but not
intracellular Ca(2+) changes in PMN or PMN adherence to HUVEC, were reduced by
ACEi treatment. Moreover, both ACEi inhibited HUVEC surface expression of
TNFalpha receptor I (but not II). Thus, these ACEi, particularly captopril,
interfere with PMN-induced cytotoxicity for endothelial cells by modulating pro
inflammatory surface receptors, which is a novel effect that might be explored
for further therapeutic approaches.
PMID- 25124789
TI - Environmental costs and renewable energy: re-visiting the Environmental Kuznets
Curve.
AB - The environmental costs of economic development have received increasing
attention during the last years. According to the World Energy Outlook (2013)
sustainable energy policies should be promoted in order to spur economic growth
and environmental protection in a global context, particularly in terms of
reducing greenhouse gas emissions that contribute to climate change. Within this
framework, the European Union aims to achieve the "20-20-20" targets, including a
20% reduction in EU greenhouse gas emissions from 1990 levels, a raise in the
share of EU energy consumption produced from renewable resources to 20% and a 20%
improvement in the EU's energy efficiency. Furthermore, the EU "Energy Roadmap
2050" has been recently adopted as a basis for developing a long-term European
energy framework, fighting against climate change through the implementation of
energy efficiency measures and the reduction of emissions. This paper focuses on
the European context and attempts to explain the impact of economic growth on CO2
emissions through the estimation of an Environmental Kuznets Curve (EKC) using
panel data. Moreover, since energy seems to be at the heart of the environmental
problem it should also form the core of the solution, and therefore we provide
some extensions of the EKC by including renewable energy sources as explanatory
variables in the proposed models. Our data sets are referred to the 27 countries
of the European Union during the period 1996-2010. With this information, our
empirical results provide some interesting evidence about the significant impacts
of renewable energies on CO2 emissions, suggesting the existence of an extended
EKC.
PMID- 25124790
TI - Capturing multiple values of ecosystem services shaped by environmental
worldviews: a spatial analysis.
AB - Two related approaches to valuing nature have been advanced in past research
including the study of ecosystem services and psychological investigations of the
factors that shape behavior. Stronger integration of the insights that emerge
from these two lines of enquiry can more effectively sustain ecosystems,
economies, and human well-being. Drawing on survey data collected from outdoor
recreationists on Santa Cruz Island within Channel Islands National Park, U.S.,
our study blends these two research approaches to examine a range of tangible and
intangible values of ecosystem services provided to stakeholders with differing
biocentric and anthropocentric worldviews. We used Public Participation
Geographic Information System methods to collect survey data and a Social Values
for Ecosystem Services mapping application to spatially analyze a range of values
assigned to terrestrial and aquatic ecosystems in the park. Our results showed
that preferences for the provision of biological diversity, recreation, and
scientific-based values of ecosystem services varied across a spatial gradient.
We also observed differences that emerged from a comparison between survey
subgroups defined by their worldviews. The implications emanating from this
investigation aim to support environmental management decision-making in the
context of protected areas.
PMID- 25124791
TI - Candida glabrata endophthalmitis transmitted from graft to host after descemet
stripping automated endothelial keratoplasty.
PMID- 25124792
TI - Exploring the relationship between socioeconomic status and dog-bite injuries
through spatial analysis.
AB - INTRODUCTION: Despite a reported socioeconomic gradient in health, little is
known about relationship between socioeconomic status (SES) and frequency of dog
bite injuries. The primary objective of this study was to compare the frequency
of dog-bite injuries, using data on dog-bite injury hospitalizations (DBIH),
across different SES areas in Manitoba, Canada. The secondary objective of the
study was to assess if frequency and pattern of DBIHs are similar to those of non
canine bite injury hospitalizations (NCBIH) and rabies post-exposure prophylaxis
(PEP). SES grouping in this study was defined through rurality and area-wide
income quintile groups. METHODS: Rural and urban Manitoba neighbourhoods were
ranked according to average area-level incomes into five levels (quintiles) with
equal numbers of people in each income level. Prevalence was defined as the
number of cases of hospitalizations (whether dog-bite injury or non-canine bite
injury) or PEP reported in the years 1984-2006, divided by the total population
during the same time period and expressed as the number of cases per 100 000
population per SES grouping. The 95% confidence intervals (CI) were calculated
using the approach for Poisson distribution. RESULTS: During 1984-2006,
Manitoba's prevalence (CI) of DBIH (3.19 (2.97, 3.41) per 100 000 population) was
lower than prevalence of NCBIH (4.08 (3.84, 4.32)) and PEP (7.24 (6.92, 7.57)).
Prevalence of DBIH was higher in rural than in urban areas (DBIH: 3.58 (3.24,
3.92) vs 2.87 (2.59, 3.15), p<0.01) and higher in the lowest income quintile
areas than in the highest, whether rural (5.18 (4.24, 6.26) vs 3.29 (2.55, 4.17),
p<0.0001) or urban (3.65 (2.97, 4.44) vs 2.24 (1.73, 2.87), p<0.01). The patterns
of relationship between SES (rurality and income levels) and prevalence of NCBIH
and PEP were similar to those between SES and DBIH. CONCLUSIONS: Although only a
descriptive study, the results suggest that policies for control of dog-bite
injuries should be area-specific. Prevention efforts could perhaps be improved by
focussing not only on families, but also on neighbourhood regions.
PMID- 25124793
TI - Dynamic respiratory endoscopic findings pre- and post laryngoplasty in
Thoroughbred racehorses.
AB - REASONS FOR PERFORMING STUDY: To investigate laryngeal function in cases of
recurrent laryngeal neuropathy pre- and post laryngoplasty (LP) using dynamic
respiratory endoscopy (DRE). OBJECTIVES: To compare the rima glottidis area
during DRE pre- and post LP; document all forms of dynamic upper airway
obstruction (DUAO) pre- and post LP and investigate the relationship between post
operative abduction at rest and exercise. STUDY DESIGN: Prospective case series.
METHODS: Thoroughbred racehorses with pre- and post LP DRE were included. Left-to
right arytenoid cartilage angle ratios and rima glottidis area ratios were used
to quantify laryngeal function during rest and exercise, pre- and post LP.
RESULTS: In 35 horses, mean pre-LP ratios were greater during rest (left-to-right
quotient angle ratio [LRQ] 0.76 +/- 0.13; left-to-right arytenoid ratio [LRR]
0.72 +/- 0.14; rima glottidis area ratio [RGA] 0.40 +/- 0.10) than exercise (LRQ
0.39 +/- 0.16, P < 0.001; LRR 0.38 +/- 0.16, P < 0.001; RGA 0.15 +/- 0.05, P <
0.001). Exercising ratios were larger post LP (LRQ 0.61 +/- 0.13; LRR 0.60 +/-
0.12; RGA 0.30 +/- 0.08) than pre-LP (LRQ 0.39 +/- 0.16, P < 0.001; LRR 0.38 +/-
0.16, P < 0.001; RGA 0.15 +/- 0.05, P < 0.001). A positive linear relationship
was found between post LP resting and exercising ratios (R(2) = 0.48; P < 0.001)
and post operative abduction grades (R(2) = 0.63; P < 0.001). Pre-LP all horses
demonstrated left arytenoid cartilage collapse with bilateral vocal cord collapse
and 37% had aryepiglottic fold collapse. Post LP 13 horses (37%) developed
additional DUAOs and these horses had smaller RGAs (0.25 +/- 0.08) than horses
that did not develop DUAOs (0.32 +/- 0.07, P = 0.01). CONCLUSIONS: Multiple forms
of DUAO occurred pre-LP and additional forms often developed post LP. Post LP the
degree of arytenoid cartilage abduction at rest was useful to predict the degree
of abduction during exercise.
PMID- 25124795
TI - Intriguing manipulation of metal-enhanced fluorescence for the detection of
Cu(II) and cysteine.
AB - Commercially available salicylaldehyde, in alkaline medium, exhibits strong
fluorescence after one hour of UV exposure in the presence of Ag(I) . The
phenolic group of salicylaldehyde is converted into the quinone form under
alkaline conditions in the presence of AgNO3 , resulting in aggregated Ag(0),
which causes approximately 250 times fluorescence enhancement of the in situ
produced quinone. Such high silver-enhanced-fluorescence (SEF) is selectively
quenched by cysteine, arginine, histidine, methionine, and tryptophan. In
contrast to the other amino acids, ageing brings selectivity of the cysteine
induced quenching effect. Interestingly, Cu(II) is found to be the only metal ion
that exclusively regenerates the lost fluorescence. Thus, quenching and recovery
of fluorescence (Turn Off/On) can be used for the selective and sensitive
detection of cysteine as well as Cu(II) ions in one pot. Alteration of the
electric field density around the fluorophore (lightening rod effect) and
scattering/absorption cross-section have been proposed to account for the Off/On
fluorescence.
PMID- 25124794
TI - Serum immunoglobulin E and interleukin-13 levels in children with idiopathic
nephrotic syndrome.
AB - Serum IgE and IL-13 levels were estimated in 40 idiopathic nephrotic syndrome and
16 controls. There were 15 first episode nephrotic syndrome (FENS), 15 infrequent
relapsing nephrotic syndrome (IRNS) and 10 patients belonged to frequent
relapsing nephrotic syndrome (FRNS). Serum IgE and IL-13 levels were
significantly increased in active nephrotic syndrome and its sub-groups as
compared to controls and remission (p < 0.001). IgE levels did not differ
significantly among different subgroups, while Il-13 was significantly higher in
FRNS in comparison with FENS (p = 0.041). Both IgE and IL-13 levels were
comparable in nephrotic patients with and without bronchial asthma. Serum IL-13
had significant positive correlation with IgE (r = 0.605, p < 0.001). Thus,
raised levels of IgE and IL-13 are found in nephrotic syndrome and could have a
role in the pathogenesis of disease.
PMID- 25124797
TI - Plane-wave density functional theory investigation of adsorption of 2,4,6
trinitrotoluene on Al-hydroxylated (0001) surface of (4 * 4) alpha-alumina.
AB - This article reports the results of the theoretical investigation of adsorption
of 2,4,6-trinitrotoluene (TNT) on Al-hydroxylated (0001) surface of (4 * 4) alpha
alumina (alpha-Al2O3) using plane-wave Density Functional Theory. Sixteen water
molecules were used to hydroxylate the alumina surface. The Perdew-Burke
Ernzerhof functional and the recently developed van der Waals functional (vdW
DF2) were used. The interaction of electron with core was accounted using the
Vanderbilt ultrasoft pseudopotentials. It was found that hydroxylation has
significant influence on the geometry of alumina and such changes are prominent
up to few layers from the surface. Particularly, due to the Al-hydroxylation the
oxygen layers are decomposed into sublayers and such partitioning becomes
progressively weaker for interior layers. Moreover, the nature of TNT adsorption
interaction is changed from covalent type on the pristine alumina surface to
hydrogen-bonding interaction on the Al-hydroxylated alumina surface. TNT in
parallel orientation forms several hydrogen bonds compared to that in the
perpendicular orientation with hydroxyl groups of the Al-hydroxylated alumina
surface. Therefore, the parallel orientation will be present in the adsorption of
TNT on Al-hydroxylated (0001) surface of alpha-alumina. Further, the vdW-DF2 van
der Waals functional was found to be most suitable and should be used for such
surface adsorption investigation.
PMID- 25124796
TI - Snail regulated by PKC/GSK-3beta pathway is crucial for EGF-induced epithelial
mesenchymal transition (EMT) of cancer cells.
AB - Cancer metastasis is considered a major challenge in cancer therapy. Recently,
epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR) signaling
has been shown to induce epithelial-mesenchymal transition (EMT) and thereby to
promote cancer metastasis. However, the underlying mechanism has not been fully
elucidated. We demonstrate that EGF can induce EMT in human prostate and lung
cancer cells and thus promote invasion and migration. EGF-induced EMT has been
characterized by the cells acquiring mesenchymal spindle-like morphology and
increasing their expression of N-cadherin and fibronectin, with a concomitant
decrease of E-cadherin. Both protein and mRNA expression of transcription factor
Snail rapidly increases after EGF treatment. The knockdown of Snail significantly
attenuates EGF-induced EMT, suggesting that Snail is crucial for this process. To
determine the way that Snail is accumulated, we demonstrate (1) that EGF promotes
the stability of Snail via inhibiting the activity of glycogen synthase kinase 3
beta (GSK-3beta), (2) that protein kinase C (PKC) rather than the
phosphatidylinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is
responsible for GSK-3beta inhibition and (3) that GSK-3beta inhibition promotes
the transcription of Snail. Taken together, these results reveal that the PKC/GSK
3beta signaling pathway controls both the stability and transcription of Snail,
which is crucial for EMT induced by EGF in PC-3 and A549 cells. Our study
suggests a novel signaling pathway for Snail regulation and provides a better
understanding of growth-factor-induced tumor EMT and metastasis.
PMID- 25124801
TI - Advanced drug delivery systems for therapeutic applications.
PMID- 25124804
TI - Phenotypic plasticity and similarity among gall morphotypes on a superhost,
Baccharis reticularia (Asteraceae).
AB - Understanding factors that modulate plant development is still a challenging task
in plant biology. Although research has highlighted the role of abiotic and
biotic factors in determining final plant structure, we know little of how these
factors combine to produce specific developmental patterns. Here, we studied
patterns of cell and tissue organisation in galled and non-galled organs of
Baccharis reticularia, a Neotropical shrub that hosts over ten species of galling
insects. We employed qualitative and quantitative approaches to understand
patterns of growth and differentiation in its four most abundant gall
morphotypes. We compared two leaf galls induced by sap-sucking Hemiptera and stem
galls induced by a Lepidopteran and a Dipteran, Cecidomyiidae. The hypotheses
tested were: (i) the more complex the galls, the more distinct they are from
their non-galled host; (ii) galls induced on less plastic host organs, e.g.
stems, develop under more morphogenetic constraints and, therefore, should be
more similar among themselves than galls induced on more plastic organs. We also
evaluated the plant sex preference of gall-inducing insects for oviposition.
Simple galls were qualitative and quantitatively more similar to non-galled
organs than complex galls, thereby supporting the first hypothesis. Unexpectedly,
stem galls had more similarities between them than to their host organ, hence
only partially supporting the second hypothesis. Similarity among stem galls may
be caused by the restrictive pattern of host stems. The opposite trend was
observed for host leaves, which generate either similar or distinct gall
morphotypes due to their higher phenotypic plasticity. The Relative Distance of
Plasticity Index for non-galled stems and stem galls ranged from 0.02 to 0.42.
Our results strongly suggest that both tissue plasticity and gall inducer
identity interact to determine plant developmental patterns, and therefore, final
gall structure.
PMID- 25124805
TI - Assessment of 5-fluorouracil and 4-nitroquinoline-1-oxide in vivo genotoxicity
with Pig-a mutation and micronucleus endpoints.
AB - Genotoxicity assessments were conducted on male Sprague Dawley rats treated with
5-fluorouracil (5-FU) and 4-nitroquinoline-1-oxide (4NQO) as part of an
international validation trial of the Pig-a mutant phenotype assay. Rats were
orally exposed to 0, 11.5, 23, or 46 mg/kg/day 5-FU for three consecutive days
(Days 1-3); blood was sampled on Days -1, 4, 15, 29, and 45. Pig-a mutant
phenotype reticulocyte (RET(CD59-)) and mutant phenotype erythrocyte (RBC(CD59-))
frequencies were determined on Days -1, 15, 29, and 45, and percent
micronucleated reticulocytes (%MN-RET) were measured on Day 4. Rats were treated
with 4NQO for 28 consecutive days by oral gavage, at doses of 1.5, 3, or 6
mg/kg/day. RBC(CD59-) and RET(CD59-) frequencies were determined on Days -1, 15,
and 29, and MN-RET were quantified on Day 29. Whereas 5-FU was found to increase
%MN-RET, no significant increases were observed for RBC(CD59-) or RET(CD59-) at
any of the time points studied. The high dose of 4NQO (6 mg/kg/day) was observed
to markedly increase RBC(CD59-) and RET(CD59-) frequencies, and this same dose
level caused a weak but significantly elevated increase in MN-RET (approximately
twofold). Collectively, the results provide additional support for the
combination of Pig-a mutation and MN-RET into acute and 28-day repeat-dose
studies.
PMID- 25124806
TI - Feasibility study to assess clinical applications of 3-T cine MRI coupled with
synchronous audio recording during speech in evaluation of velopharyngeal
insufficiency in children.
AB - BACKGROUND: In the past decade, there has been increased utilization of magnetic
resonance imaging (MRI) in evaluating and understanding velopharyngeal
insufficiency (VPI). To our knowledge, none of the prior studies with MRI has
simultaneously linked the audio recordings of speech during cine MRI acquisition
with the corresponding images and created a video for evaluating VPI. OBJECTIVE:
To develop an MRI protocol with static and cine sequences during phonation to
evaluate for VPI in children and compare the findings to nasopharyngoscopy and
videofluoroscopy. MATERIALS AND METHODS: Five children, ages 8-16 years, with
known VPI, who had previously undergone nasopharyngoscopy and videofluoroscopy,
were included. MRI examination was performed on a 3-T Siemens scanner. Anatomical
data was obtained using an isotropic T2-weighted 3-D SPACE sequence with
multiplanar reformation capability. Dynamic data was obtained using 2-D FLASH
cine sequences of the airway in three imaging planes during phonation. Audio
recordings were captured by a MRI compatible optical microphone. RESULTS: All
five cases had MRI and nasopharyngoscopy and four had videofluoroscopy performed.
VPI was identified by MRI in all five patients. The location and severity of the
velopharyngeal gap, closure pattern, velar size and shape and levator veli
palatini (LVP) muscle were identified in all patients. MRI was superior in
visualizing the integrity of the LVP muscle. MRI was unable to identify
hemipalatal weakness in one case. In a case of stress-induced VPI, occurring only
during clarinet playing, cine MRI demonstrated discordant findings of a
velopharyngeal gap during phonatory tasks but not with instrument playing.
Overall, there was satisfactory correlation among MRI, nasopharyngoscopy and
videofluoroscopy findings. CONCLUSION: Cine MRI of the airway during speech is a
noninvasive, well-tolerated diagnostic imaging tool that has the potential to
serve as a guide prior to and after surgical correction of VPI. MRI provided
superior anatomical detail of the levator musculature. The creation of a video
with recorded phonation allowed correlation between palatal movements and
specific phonatory tasks.
PMID- 25124808
TI - 8-Azapurines as isosteric purine fluorescent probes for nucleic acid and
enzymatic research.
AB - The 8-azapurines, and their 7-deaza and 9-deaza congeners, represent a unique
class of isosteric (isomorphic) analogues of the natural purines, frequently
capable of substituting for the latter in many biochemical processes.
Particularly interesting is their propensity to exhibit pH-dependent room
temperature fluorescence in aqueous medium, and in non-polar media. We herein
review the physico-chemical properties of this class of compounds, with
particular emphasis on the fluorescence emission properties of their neutral
and/or ionic species, which has led to their widespread use as fluorescent probes
in enzymology, including enzymes involved in purine metabolism,
agonists/antagonists of adenosine receptors, mechanisms of catalytic RNAs, RNA
editing, etc. They are also exceptionally useful fluorescent probes for
analytical and clinical applications in crude cell homogenates.
PMID- 25124809
TI - Unexpected positive intraoperative cultures in aseptic revision arthroplasty.
AB - Unexpected positive intraoperative cultures (UPIC) in presumed aseptic revision
arthroplasty can be difficult to interpret. The purpose of this retrospective
study was to compare the incidence of subsequent periprosthetic joint infection
(PJI) in patients who received antibiotic therapy according to an institutional
protocol with those who did not and whether they meet Musculoskeletal Infection
Society (MSIS) criteria for PJI. In patients who were treated with antibiotic
according to institutional criteria, the incidence of PJI after revision was
higher in those who did not meet MSIS criteria (22%) than in those that met MSIS
criteria (14%; P > 0.71). UPIC in aseptic revision arthroplasty are not uncommon.
PJI cannot be excluded in patients that do not meet MSIS definition.
PMID- 25124812
TI - Multiple populations of pantropical spotted dolphins in Hawaiian waters.
AB - Understanding gene flow and dispersal patterns is important for predicting
effects of natural events and anthropogenic activities on animal populations. In
Hawaii, most species of odontocetes are managed as single populations. Recent
exceptions include false killer whales, spinner dolphins, and common bottlenose
dolphins, for which studies have shown fidelity to individual islands or groups
of islands. Our study focused on pantropical spotted dolphins. We analyzed
mitochondrial control region and 11 microsatellite loci from 101 individuals from
4 areas: Hawaii, Maui/Lanai, Oahu, and Kauai/Niihau. We examined F ST, F' ST, R
ST, Jost's D, and PhiST and used TESS to estimate number of populations and
assignment probabilities. Our results support genetic differentiation among
Hawaii, Maui/Lanai, and Oahu and suggest that pantropical spotted dolphins near
Kauai/Niihau are likely transient and in low numbers. Between island regions, F
ST for microsatellites ranged from 0.016 to 0.045 and for mtDNA, from 0.011 to
0.282. F ' ST, ranged from 0.098 to 0.262 for microsatellites and 0.019 to 0.415
for mtDNA. R ST and PhiST showed similar results to F ST for microsatellites and
mtDNA respectively, and Jost's D fell between F ST and F ' ST. TESS supported 3
populations, and greatest mean assignment probability by island region ranged
from 0.50 to 0.72. The private alleles method indicated migration rates among
regions from 1.49 to 3.45, and effective population size of the island of Hawaii
was estimated to be 220. There was no strong evidence to support sex-biased
dispersal or group fidelity. Considering this study in the larger context of
other odontocete population studies and studies of connectivity, we suggest
genetic differentiation may be mediated by behavior adapted to differing habitat
types and niches.
PMID- 25124813
TI - Contrasting levels of clonal and within-population genetic diversity between the
2 ecologically different herbs Polygonatum stenophyllum and Polygonatum inflatum
(Liliaceae).
AB - Comparative studies on clonal and genetic structure between ecologically
contrasting congeners may provide valuable insights into the mechanisms promoting
the maintenance of genetic diversity in clonal plant species. Polygonatum
stenophyllum has long rhizomes (ca. 30-40 cm long) and largely occurs on sandy
soils in open river banks, whereas its congener Polygonatum inflatum has short
ones (ca. 5-10 cm long) and occurs on humic soils under deciduous forests. Using
21 allozyme loci, we comparatively assessed levels of clonal and genetic
diversity in the 2 clonal species. Seven populations of P. stenophyllum consisted
of single clones, and levels of within-population clonal and genetic variation
were considerably lower than those of P. inflatum. However, when samples were
pooled, P. stenophyllum harbored higher genetic variation than P. inflatum, which
is due to higher among-population genetic differentiation in the former species
compared with the latter (FST=0.636 vs. FST=0.165). Our data suggest that
populations of P. stenophyllum have been mainly founded by a single seed or
rhizome (through river water) or by a few seeds, whereas populations of P.
inflatum would have been established through multiple, repeated seedling
recruitment. Moderate levels of genetic diversity in a population of P.
stenophyllum located at the foot of the Baekdudaegan Mountains and in all the
populations of P. inflatum are consistent with the previous hypothesis that these
mountains served as a glacial refugium for many boreal species of the Korean
Peninsula.
PMID- 25124814
TI - Outcomes of Fukushima: biological effects of radiation on nonhuman species.
PMID- 25124807
TI - Cerebrospinal fluid markers of neuroinflammation in delirium: a role for
interleukin-1beta in delirium after hip fracture.
AB - OBJECTIVE: Exaggerated central nervous system (CNS) inflammatory responses to
peripheral stressors may be implicated in delirium. This study hypothesised that
the IL-1beta family is involved in delirium, predicting increased levels of
interleukin-1beta (IL-1beta) and decreased IL-1 receptor antagonist (IL-1ra) in
the cerebrospinal fluid (CSF) of elderly patients with acute hip fracture. We
also hypothesised that Glial Fibrillary Acidic Protein (GFAP) and interferon
gamma (IFN-gamma) would be increased, and insulin-like growth factor 1 (IGF-1)
would be decreased. METHODS: Participants with acute hip fracture aged >60 (N=43)
were assessed for delirium before and 3-4 days after surgery. CSF samples were
taken at induction of spinal anaesthesia. Enzyme-linked immunosorbent assays
(ELISA) were used for protein concentrations. RESULTS: Prevalent delirium was
diagnosed in eight patients and incident delirium in 17 patients. CSF IL-1beta
was higher in patients with incident delirium compared to never delirium
(incident delirium 1.74 pg/ml (1.02-1.74) vs. prevalent 0.84 pg/ml (0.49-1.57)
vs. never 0.66 pg/ml (0-1.02), Kruskal-Wallis p=0.03). CSF:serum IL-1beta ratios
were higher in delirious than non-delirious patients. CSF IL-1ra was higher in
prevalent delirium compared to incident delirium (prevalent delirium 70.75 pg/ml
(65.63-73.01) vs. incident 31.06 pg/ml (28.12-35.15) vs. never 33.98 pg/ml (28.71
43.28), Kruskal-Wallis p=0.04). GFAP was not increased in delirium. IFN-gamma and
IGF-1 were below the detection limit in CSF. CONCLUSION: This study provides
novel evidence of CNS inflammation involving the IL-1beta family in delirium and
suggests a rise in CSF IL-1beta early in delirium pathogenesis. Future larger CSF
studies should examine the role of CNS inflammation in delirium and its sequelae.
PMID- 25124811
TI - In vivo growth suppression of CT-26 mouse colorectal cancer cells by adenovirus
expressed small hairpin RNA specifically targeting thymosin beta-4 mRNA.
AB - Thymosin beta-4 (Tbeta4) is known to be involved in tumorigenesis. Overexpression
of this polypeptide has been observed in a wide variety of cancers, including
colorectal carcinoma (CRC). Accordingly, Tbeta4 has been proposed to be a novel
therapeutic target for CRC, especially in its metastatic form. Although in vitro
tumor-suppressive effects of Tbeta4 gene silencing mediated by small hairpin RNA
(shRNA) have already been demonstrated, the in vivo efficacy of such an approach
has not yet been reported. Herein, we demonstrated that infection with
recombinant adenovirus expressing an shRNA targeting Tbeta4 markedly reduced the
growth of and robustly induced apoptosis in CT-26 mouse CRC cells in culture.
Additionally, tumors grown in nude mice from the CT-26 cells whose Tbeta4
expression already been downregulated by virus infection were also drastically
reduced. Most importantly, significant growth arrest of tumors derived from the
parental CT-26 cells was observed after multiple intratumoral injections of these
viruses. Together, our results show for the first time that in vivo silencing of
Tbeta4 expression by its shRNA generated after adenoviral infection can suppress
CRC growth. These results further demonstrate the feasibility of treating CRC by
a Tbeta4 knockdown gene therapeutic approach.
PMID- 25124815
TI - Genetic and ecological studies of animals in Chernobyl and Fukushima.
AB - Recent advances in genetic and ecological studies of wild animal populations in
Chernobyl and Fukushima have demonstrated significant genetic, physiological,
developmental, and fitness effects stemming from exposure to radioactive
contaminants. The few genetic studies that have been conducted in Chernobyl
generally show elevated rates of genetic damage and mutation rates. All major
taxonomic groups investigated (i.e., birds, bees, butterflies, grasshoppers,
dragonflies, spiders, mammals) displayed reduced population sizes in highly
radioactive parts of the Chernobyl Exclusion Zone. In Fukushima, population
censuses of birds, butterflies, and cicadas suggested that abundances were
negatively impacted by exposure to radioactive contaminants, while other groups
(e.g., dragonflies, grasshoppers, bees, spiders) showed no significant declines,
at least during the first summer following the disaster. Insufficient information
exists for groups other than insects and birds to assess effects on life history
at this time. The differences observed between Fukushima and Chernobyl may
reflect the different times of exposure and the significance of multigenerational
mutation accumulation in Chernobyl compared to Fukushima. There was considerable
variation among taxa in their apparent sensitivity to radiation and this reflects
in part life history, physiology, behavior, and evolutionary history.
Interestingly, for birds, population declines in Chernobyl can be predicted by
historical mitochondrial DNA base-pair substitution rates that may reflect
intrinsic DNA repair ability.
PMID- 25124816
TI - Fukushima's biological impacts: the case of the pale grass blue butterfly.
AB - To evaluate the effects of the Fukushima nuclear accident on the surrounding
area, we studied the pale grass blue butterfly Zizeeria maha, the most common
butterfly in Japan. We here review our important findings and their implications.
We found forewing size reduction, growth retardation, high mortality rates, and
high abnormality rates in the field and reared samples. The abnormality rates
observed in September 2011 were higher than those observed in May 2011 in almost
all localities, implying transgenerational accumulation of genetic damage. Some
of the abnormal traits in the F1 generation were inherited by the F2 generation.
In a particular cross, the F2 abnormality rate scored 57%. The forewing size
reduction and high mortality and abnormality rates were reproduced in external
and internal exposure experiments conducted in our laboratory using Okinawa
larvae. We observed the possible real-time evolution of radiation resistance in
the Fukushima butterflies, which, in retrospect, indicates that field sampling
attempts at the very early stages of such accidents are required to understand
the ecodynamics of polluted regions. We propose, as the postulates of pollutant
induced biological impacts, that the collection of phenotypic data from the field
and their relevant reproduction in the laboratory should be the basis of
experimental design to demonstrate the biological effects of environmental
pollutants and to investigate the molecular mechanisms responsible for these
effects.
PMID- 25124817
TI - Unraveling low-level gamma radiation--responsive changes in expression of early
and late genes in leaves of rice seedlings at Iitate Village, Fukushima.
AB - In the summer of 2012, 1 year after the nuclear accident in March 2011 at the
Fukushima Daiichi nuclear power plant, we examined the effects of gamma radiation
on rice at a highly contaminated field of Iitate village in Fukushima, Japan. We
investigated the morphological and molecular changes on healthy rice seedlings
exposed to continuous low-dose gamma radiation up to 4 uSv h(-1), about 80 times
higher than natural background level. After exposure to gamma rays, expression
profiles of selected genes involved in DNA replication/repair, oxidative stress,
photosynthesis, and defense/stress functions were examined by RT-PCR, which
revealed their differential expression in leaves in a time-dependent manner over
3 days (6, 12, 24, 48, and 72 h). For example, OsPCNA mRNA rapidly increased at
6, 12, and 24 h, suggesting that rice cells responded to radiation stress by
activating a gene involved in DNA repair mechanisms. At 72 h, genes related to
the phenylpropanoid pathway (OsPAL2) and cell death (OsPR1oa) were strongly
induced, indicating activation of defense/stress responses. We next profiled the
transcriptome using a customized rice whole-genome 4*44K DNA microarray at early
(6h) and late (72 h) time periods. Low-level gamma radiation differentially
regulated rice leaf gene expression (induced 4481 and suppressed 3740 at 6 h and
induced 2291 and suppressed 1474 genes at 72 h) by at least 2-fold. Using the
highly upregulated and downregulated gene list, MapMan bioinformatics tool
generated diagrams of early and late pathways operating in cells responding to
gamma ray exposure. An inventory of a large number of gamma radiation-responsive
genes provides new information on novel regulatory processes in rice.
PMID- 25124824
TI - Exploring associations between lower urinary tract symptoms (LUTS) and
gastrointestinal (GI) problems in women: a study in women with urological and GI
problems vs a control population.
AB - OBJECTIVES: To study the prevalence of self-reported lower urinary tract symptoms
(LUTS) in women consulting a Gastroenterology clinic with complaints of
functional constipation (FC), fecal incontinence (FI) or both, compared with a
female control population. Also, to study the influence of FC, FI, or both on
self-reported LUTS in women attending a Urology clinic. PATIENTS AND METHODS: We
present a retrospective study of data collected through a validated self
administered bladder and bowel symptom questionnaire in a tertiary referral
hospital from three different female populations: 104 controls, 159
gastroenterological patients and 410 urological patients. Based on the reported
bowel symptoms, patients were classified as having FC, FI, a combination of both,
or, no FC or FI. LUTS were compared between the control population and the
gastroenterological patients, and between urological patients with and without
concomitant gastroenterological complaints. Results were corrected for possible
confounders through logistic regression analysis. RESULTS: The prevalence of LUTS
in the control population was similar to large population-based studies. Nocturia
was significantly more prevalent in gastroenterological patients with FI compared
with the control population [odds ratio (OR) 9.1]. Female gastroenterological
patients with FC more often reported straining to void (OR 10.3), intermittency
(OR 5.5), need to immediately re-void (OR 3.7) and feeling of incomplete emptying
(OR 10.5) compared with the control population. In urological patients, urgency
(94%) and urgency urinary incontinence (UUI, 54% of UI) were reported more often
by patients with FI than by patients without gastroenterological complaints (58%
and 30% of UI respectively), whereas intermittency (OR 3.6), need to immediately
re-void (OR 2.2) and feeling of incomplete emptying (OR 2.2) were reported more
often by patients with FC than by patients without gastroenterological
complaints. CONCLUSION: As LUTS are reported significantly more often by female
gastroenterological patients than by a control population, and as there is a
difference in self-reported LUTS between female urological patients with
different concomitant gastroenterological complaints, we suggest that general
practitioners, gastroenterologists and urologists should always include the
assessment of symptoms of the other pelvic organ system in their patient
evaluation. The clinical correlations between bowel symptoms and LUTS may be
explained by underlying neurological mechanisms.
PMID- 25124823
TI - Pachyonychia congenita cornered: report on the 11th Annual International
Pachyonychia Congenita Consortium Meeting.
AB - This is a report of the research presented at the 11th Annual Meeting of the
International Pachyonychia Congenita Consortium, held on 6 May 2014 in
Albuquerque, NM, U.S.A. This year's meeting was divided into five corners
concerning pachyonychia congenita (PC) research: (i) 'PC Pathogenesis Cornered',
an overview of recent keratin research, for PC and other skin disorders; (ii)
'From All Corners of ...', an outline of other genetic disorders that we can
learn from; (iii) 'Fighting For Our Corner', an outline of National Institutes of
Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases
programmes and U.S. funding opportunities applicable to rare skin disorders; (iv)
'The PC Corner', focusing on recent clinical studies related to PC; and (v)
'Clinical Corners: Turning the Corner?', an update on ongoing PC clinical trials.
PMID- 25124825
TI - The effect of beta blocker withdrawal on adenosine myocardial perfusion imaging.
AB - BACKGROUND: The effect of beta blockers on myocardial blood flow (MBF) under
vasodilators has been studied in several SPECT and PET myocardial perfusion
imaging (MPI) studies with divergent results. The present study evaluated the
effect of a beta blocker withdrawal on quantitative adenosine MBF and on MPI
results. METHODS: Twenty patients with beta blockers and CAD history were studied
with quantitative adenosine N-13 ammonia PET. The first study was performed under
complete medication and the second after beta blocker withdrawal. The PET studies
were independently read with respect to MPI result and clinical decision making.
RESULTS: Global MBF showed an increase from 180.2 +/- 59.9 to 193.6 +/- 60.8
mL.minute(-1)/100 g (P = .02) after beta blocker withdrawal. The segmental
perfusion values were closely correlated (R(2) = 0.82) over the entire range of
perfusion values. An essentially different interpretation after beta blocker
discontinuation was found in two cases (10%). CONCLUSION: A beta blocker
withdrawal induces an increase in adenosine MBF. In the majority of cases, MPI
interpretation and decision making are independent of beta blocker intake. If a
temporary beta blocker withdrawal before MPI is not possible or was not realized
by the patient, it is appropriate to perform adenosine stress testing without
loss of the essential MPI result.
PMID- 25124828
TI - Does risk for major adverse cardiac events in patients undergoing vasodilator
stress with adjunctive exercise differ from patients undergoing either standard
exercise or vasodilator stress with myocardial perfusion imaging?
AB - BACKGROUND: In patients with functional limitations, the use of adjunctive
exercise with vasodilator stress has advantages over vasodilator stress alone in
single photon emission computed tomography myocardial perfusion imaging (MPI) for
technical reasons and with regards to more effective cardiac risk stratification.
Whether patients who undergo vasodilator with adjunctive exercise stress MPI
possess clinical characteristics and cardiac risk that differs from those who
undergo standard exercise or vasodilator stress MPI is unknown. METHODS:
Prospectively collected data on 19,367 consecutive patients referred for stress
MPI to a tertiary care center (9,331 [48%] underwent exercise-only, 3,793 [20%]
underwent vasodilator plus exercise, and 6,243 [32%] underwent vasodilator-only)
were analyzed. Perfusion data were scored using the ASNC 17-segment with a summed
stress score (SSS) < 4 = normal, 4-8 = mildly abnormal, and > 8 = moderate to
severely abnormal. Patients were followed a mean of 1.96 +/- 0.95 years.
Demographics, clinical characteristics, and the occurrence of major adverse
cardiac events (cardiac death or nonfatal myocardial infarction) were compared
between the three stress modality groups. RESULTS: Comparison of demographics and
clinical characteristics revealed significant differences in gender, age, cardiac
risk factors, and stress MPI between the three stress modality groups (P < .001).
In follow-up, cardiac event-free survival of patients in the vasodilator plus
exercise stress group was significantly higher than those in the vasodilator-only
group but lower than those in the exercise-only group (P < .001). Annualized
cardiac event rates of patients in the vasodilator plus exercise stress group
were significantly lower than those in the vasodilator-only group for all three
categories of the SSS (P < .001). After multivariable adjustment, with exercise
only as reference category, vasodilator plus exercise and vasodilator-only stress
emerged as independent predictors (more likely occurrence) of cardiac death,
while vasodilator-only stress emerged as an independent predictor (more likely
occurrence) of cardiac death or nonfatal myocardial infarction. With vasodilator
only as the reference category, exercise-only and vasodilator plus exercise
stress emerged as independent predictors (less likely occurrence) of cardiac
death as well as of cardiac death or nonfatal myocardial infarction. CONCLUSIONS:
Patients undergoing vasodilator plus exercise stress MPI possess clinical
characteristics and cardiac risk that differs significantly from those undergoing
either standard exercise or vasodilator stress MPI and places them in a lower
risk category compared to vasodilator stress alone.
PMID- 25124826
TI - Comparison of Tc-99m tetrofosmin myocardial perfusion scintigraphy and exercise
F18-FDG imaging in detection of myocardial ischemia in patients with coronary
artery disease.
AB - BACKGROUND: Direct ischemia imaging with F18-FDG can potentially overcome many
limitations of SPECT-MPS inherent to "cold imaging". We compared SPECT-MPS with
exercise F18-FDG PET in detection of ischemia in patients with suspected CAD.
METHODS: 45 patients with clinical suspicion of CAD without the history of
myocardial infarction were prospectively included. All patients underwent Tc-99m
tetrofosmin SPECT-MPS and exercise F18-FDG PET imaging within 7 days of SPECT
MPS, and both modalities were compared with coronary angiography for detecting
ischemia. RESULTS: 27 patients had an abnormal coronary angiography (at least one
coronary artery with stenosis >50%). Exercise F18-FDG performed better than SPECT
MPS in LAD and LCX territory with comparably good performance in RCA territory.
Exercise F18-FDG performed better in single-vessel disease and equally good in
multi-vessel disease compared to SPECT-MPS. Performance of exercise 18F-FDG study
was significantly better than SPECT-MPS (P = .0014) in the analysis of the 81
vascular territories in the 27 patients with abnormal coronary angiography.
Performance of exercise F18-FDG was significantly better than SPECT-MPS in
detecting ischemia in suspected CAD patients. CONCLUSION: Exercise F18-FDG
imaging is a potentially useful ischemia imaging modality which offers the
advantages of direct ischemia imaging in CAD patients.
PMID- 25124827
TI - Molecular imaging of plaque vulnerability.
AB - Over the past decade, significant progress has been made in the development of
novel imaging strategies focusing on the biology of the vessel wall for
identification of vulnerable plaques. While the majority of these studies are
still in the pre-clinical stage, few techniques (e.g., (18)F-FDG and (18)F-NaF
PET imaging) have already been evaluated in clinical studies with promising
results. Here, we will briefly review the pathobiology of atherosclerosis and
discuss molecular imaging strategies that have been developed to target these
events, with an emphasis on mechanisms that are associated with atherosclerotic
plaque vulnerability.
PMID- 25124830
TI - Synthesis of highly active and stable spinel-type oxygen evolution
electrocatalysts by a rapid inorganic self-templating method.
AB - Composition-adjustable spinel-type metal oxides, Mnx Co3-x O4-delta (x=0.8-1.4),
were synthesized in ethanol solutions by a rapid inorganic self-templating
mechanism using KCl nanocrystals as the structure-directing agent. The Mnx Co3?x
O4?delta materials showed ultrahigh oxygen evolution activity and strong
durability in alkaline solutions, and are capable of delivering a current density
of 10 mA cm(-2) at 1.58 V versus the reversible hydrogen electrode in 0.1 M KOH
solution, which is superior in comparison to IrO2 catalysts under identical
experimental conditions, and comparable to the most active noble-metal and
transition-metal oxygen evolution electrocatalysts reported so far. The high
performance for catalytic oxygen evolution originates from both compositional and
structural features of the synthesized materials. The moderate content of Mn
doping into the spinel framework led to their improved electronic conductivity
and strong oxidizing ability, and the well-developed porosity, accompanied with
the high affinity between OH(-) reactants and catalyst surface, contributed to
the smooth mass transport, thus endowing them with superior oxygen evolution
activity.
PMID- 25124829
TI - Treatment failure in cognitive-behavioural therapy: therapeutic alliance as a
precondition for an adherent and competent implementation of techniques.
AB - OBJECTIVES: Treatment failure is a common phenomenon, but little is known about
the reasons. Therapeutic alliance, therapist adherence, and therapist competence
are considered important aspects of treatment success and formed the focus of the
current investigation. DESIGN: Three randomized controlled trials for the
treatment of depression, social phobia, and hypochondriasis were the basis of the
current study. METHODS: The role of therapeutic alliance, as well as therapist
adherence and competence, were investigated in 61 patients, which were classified
either as treatment failure or as treatment success. Process variables were
evaluated by independent raters on the basis of videotapes of the first three
treatment sessions. RESULTS: Therapists' adherence and therapeutic alliance
differed significantly between successful treatments and those classified as
failures, whereas therapists' competence did not. In cross-sectional analysis, we
found a moderating effect of adherence with alliance on treatment outcome,
indicating that the better the therapeutic alliance, the stronger the effect of
adherence on treatment outcome. Moreover, higher therapists' competence was found
to affect treatment outcome positively, only mediated by therapeutic alliance.
Higher therapists' adherence affected treatment outcome positively, only mediated
by the competence-alliance relationship. In additional longitudinal analyses, we
found evidence that the therapeutic alliance within one session influences
therapists' adherence and competence in the subsequent session, but not the other
way around. CONCLUSIONS: Therapeutic alliance proved to be an important variable
for the prediction of treatment failure. Furthermore, in our longitudinal
analyses, we found evidence that the therapeutic alliance is a precondition for
the adherent and competent implementation of therapeutic techniques, which
questions the results of our cross-sectional analysis and of previous research.
PRACTITIONER POINTS: Clinical implications Treatment failure is associated with a
lower therapeutic alliance in cognitive-behavioural treatment. Therapeutic
alliance seems to be an important precondition for the adherent and competent
implementation of therapeutic techniques. Therapeutic alliance should be
monitored during psychotherapeutic treatment. Cautions or limitations Results are
limited to cognitive-behavioural therapy and may not be representative for other
treatment approaches. Process analyses are based on highly standardized
randomized controlled trials and may not be generalizable to routine care.
PMID- 25124831
TI - Socio-economic determinants of ownership and use of treated bed nets in Nigeria:
results from a cross-sectional study in Cross River and Bauchi States in 2011.
AB - BACKGROUND: Poor people bear a disproportionate burden of malaria and prevention
measures may not reach them well. A study carried out to examine the socio
economic factors associated with ownership and use of treated bed nets in Cross
River and Bauchi States of Nigeria took place soon after campaigns to distribute
treated bed nets. METHODS: A cross-sectional household survey about childhood
illnesses among mothers of children less than four years of age and focus group
discussions in 90 communities in each of the two states asked about household
ownership of treated bed nets and their use for children under four years old.
Bivariate and multivariate analyses examined associations between socio-economic
and other variables and these outcomes in each state. RESULTS: Some 72% of 7,685
households in Cross River and 87% of 5,535 households in Bauchi State had at
least one treated bed net. In Cross River, urban households were more likely to
possess bed nets, as were less-poor households (enough food in the last week),
those with a male head, and those from communities with a formal health facility.
In Bauchi, less-poor households and those with a more educated head were more
likely to possess nets. In households with nets, only about half of children
under four years old always slept under a net: 54% of 11,267 in Cross River and
57% of 11,277 in Bauchi. Factors associated with use of nets for young children
in Cross River were less-poor households, fewer young children in the household,
more education of the father, antenatal care of the mother, and younger age of
the child, while in Bauchi the factors were a mother with more education and
antenatal care, and younger age of the child. Some focus groups complained of
distribution difficulties, and many described misconceptions about adverse
effects of nets as an important reason for not using them. CONCLUSION: Despite a
recent campaign to distribute treated bed nets, disadvantaged households were
less likely to possess them and to use them for young children. Efforts are
needed to reach these households and to dispel fears about dangers of using
treated nets.
PMID- 25124832
TI - Is the incidence of temporomandibular disorder increased in polycystic ovary
syndrome?
AB - The prevalence of temporomandibular disorders is higher among women than men
(ratio 3:1 -9:1). Polycystic ovary syndrome(PCOS) is the most common endocrine
disorder in women, which is characterised by chronic low-grade inflammation and
excess of androgenic hormones that lead to metabolic aberrations and ovarian
dysfunction. Increased activities of various matrix metalloproteinases
(particularly MMP-2 and 9) in the serum of these patients has been reported, and
it has been hypothesised that high activities of MMP may contribute to loss of
matrix and chronic inflammation of the fibrocartilage in temporomandibular
disorders. Our aim was to evaluate the incidence of temopormandibular dysfunction
in women with PCOS compared with an age-matched, disease-free, control group. We
studied 50 patients with previously diagnosed PCOS and 50 volunteers who had
normal menstrual cycles. We made a comprehensive clinical examination of the
temporomandibular joint (TMJ) and muscles of mastication in both groups and
recorded the Visual Analogue Scores (VAS) for pain. There were significant
differences (p<0.001) in the incidence of temporomandibular disorders (n=43 (86%)
in the PCOS group compared with n=12 24% in the control group), muscle
tenderness(n=32 (64%) in the PCOS group compared with n=14 (28%) in the control
group) and pain in the TMJ (mean (SD) VAS 2.9 (2.61) compared with 0.3 (1.56). We
confirm the higher incidence and severity of disorders of the TMJ in patients
with PCOS and suspect that chronic low-grade inflammation may play a part in the
aetiology of the disease.
PMID- 25124833
TI - Attitudes towards pressure ulcer prevention: a psychometric evaluation of the
Swedish version of the APuP instrument.
AB - The primary aim was to conduct a psychometric evaluation of the Attitude towards
Pressure ulcer Prevention (APuP) instrument in a Swedish context. A further aim
was to describe and compare attitudes towards pressure ulcer prevention between
registered nurses (RNs), assistant nurses (ANs) and student nurses (SNs). In
total, 415 RNs, ANs and SNs responded to the questionnaire. In addition to
descriptive and comparative statistics, confirmatory factor analyses were
performed. Because of a lack of support for the instrument structure, further
explorative and consecutive confirmatory tests were conducted. Overall, positive
attitudes towards pressure ulcer prevention were identified for all three groups,
but SNs reported lower attitude scores on three items and a higher score on one
item compared to RNs and ANs. The findings indicated no support in this Swedish
sample for the previously reported five-factor model of APuP. Further explorative
and confirmative factor analyses indicated that a four-factor model was most
interpretable: (i) Priority (five items), (ii) Competence (three items), (iii)
Importance (three items) and (iv) Responsibility (two items). The five-factor
solution could not be confirmed. Further research is recommended to develop a
valid and reliable tool to assess nurses' attitudes towards pressure ulcer
prevention working across different settings on an international level.
PMID- 25124834
TI - Membrane protein resistance of oligo(ethylene oxide) self-assembled monolayers.
AB - As part of an effort to develop biointerfaces for structure-function studies of
integral membrane proteins (IMPs) a series of oligo(ethylene oxide) self
assembled monolayers (OEO-SAMs) were evaluated for their resistance to protein
adsorption (RPA) of IMPs on Au and Pt. Spectroscopic ellipsometry (SE) was used
to determine SAM thicknesses and compare the RPA of HS(CH2)3O(CH2CH2O)6CH3 (1),
HS(CH2)3O(CH2CH2O)6H (2), [HS(CH2)3]2CHO(CH2CH2O)6CH3 (3) and
[HS(CH2)3]2CHO(CH2CH2O)6H (4), assembled from water. For both substrates, SAM
thicknesses for 1 to 4 were found to be comparable indicating SAMs with similar
surface coverages and OEO chain order and packing densities. Fibrinogen (Fb), a
soluble plasma protein, and rhodopsin (Rd), an integral membrane G-protein
coupled receptor, adsorbed to the SAMs of 1, as expected from previous reports,
but not to the hydroxy-terminated SAMs of 2 and 4. The methoxy-terminated SAMs of
3 were resistant to Fb but, surprisingly, not to Rd. The stark difference between
the adsorption of Rd to the SAMs of 3 and 4 clearly indicate that a hydroxy
terminus of the OEO chain is essential for high RPA of IMPs. The similar
thicknesses and high RPA of the SAMs of 2 and 4 show the conditions of protein
resistance (screening the underlying substrate, packing densities, SAM order, and
conformational mobility of the OEO chains) defined from previous studies on Au
are applicable to Pt. In addition, the SAMs of 4, exhibiting the highest
resistance to Fb and Rd, were placed in contact with undiluted fetal bovine serum
for 2h. Low protein adsorption (~12.4ng/cm(2)), obtained under these more
challenging conditions, denote a high potential of the SAMs of 4 for various
applications requiring the suppression of non-specific protein adsorption.
PMID- 25124835
TI - Promising dissolution enhancement effect of soluplus on crystallized celecoxib
obtained through antisolvent precipitation and high pressure homogenization
techniques.
AB - Poor solubility and dissolution of hydrophobic drugs have become a major
challenge in pharmaceutical development. Drug nanoparticles have been widely
accepted to overcome this problem. The aim of this study was to manufacture
celecoxib nanoparticles using antisolvent precipitation and high pressure
homogenization techniques in the presence of varying concentrations of
soluplus((r)) as a hydrophilic stabilizer. Antisolvent crystallization followed
by freeze drying (CRS-FD) and antisolvent crystallization followed by high
pressure homogenization and freeze drying (HPH-FD) were used to obtain celecoxib
nanoparticles. The obtained nanoparticles were analyzed in terms of particle
size, saturation solubility, morphology (optical and scanning electron
microscopy), solid state (DSC, XRPD and FT-IR) and dissolution behavior. The
results showed that celecoxib nanoparticle can be obtained when soluplus was
added to the crystallization medium. In addition, the results showed that the
concentration of soluplus and the method used to prepare nanoparticles can
control the size and dissolution of celecoxib. Samples obtained in the presence
of 5% soluplus through HPH technique showed an excellent dissolution (90%) within
4min. It is interesting to note that celecoxib samples with high crystallinity
showed better dissolution than those celecoxib samples with high amorphous
content, although they had the same concentration of soluplus. DSC and XRPD
proved that samples obtained via HPH technique are more crystalline than the
samples obtained through only antisolvent crystallization technique.
PMID- 25124836
TI - Effect of exopolysaccharides on photocatalytic activity of ZnO nanoparticles.
AB - Zinc oxide nanoparticles (ZnO NPs) are largely used in consumer products and
industrial applications. The increased use of such materials may lead to its
release into the environment. The study used chemically synthesized ZnO NPs and
characterized by using UV-visible spectrophotometer, scanning electron
microscopy, particle size analyzer and X-ray diffraction (XRD) analysis. The mean
diameter of the particles was found to be 55+/-1.2nm. The XRD patterns exhibited
hexagonal structure for ZnO NPs. The photocatalytic property of ZnO NPs was
evaluated based on the UV-vis spectra changes of the methylene blue solution as a
function of reaction time in the presence of ZnO NPs under visible light. The
study suggests that ZnO NPs can be used as an efficient photocatalyst and the
environmental factor such as exopolysaccharides could mask the photocatalytic
activity of NPs.
PMID- 25124837
TI - Evaluation of esophagogastric junction relaxation by 4-second Integrated
Relaxation Pressure in achalasia using High Resolution Manometry with water
perfused catheters.
AB - BACKGROUND: Relaxation of the esophagogastric junction (EGJ) is now evaluated
calculating 4-second integrated relaxation pressure (4-s IRP) by high resolution
manometry (HREPT). Solid-state catheters have been used to define abnormal
values. Our aim was to evaluate 4-s IRP in esophageal achalasia using HREPT with
perfused catheters. METHODS: From June 2009 to June 2013, 936 HREPT studies have
been performed in our unit. Of these, 194 patients having treated achalasia were
excluded. Control group was constituted by 695 patients without achalasia, and 47
patients with untreated achalasia constituted the study group. HREPT was
performed with water-perfused catheters. To establish the cut-off value for 4-s
IRP that better discriminate patients with achalasia from all other patients, a
receiver operating characteristic (ROC) analysis was performed. KEY RESULTS:
Twenty three of 47 achalasia patients (49%) showed a 4-s IRP under 15 mmHg; and
seven (15%) had a value under modified Chicago criteria. A cut-off value for 4-s
IRP of 6.5 mmHg, calculated by ROC analysis, highly discriminates achalasia from
the rest of the patients and especially from scleroderma patients (area under the
curve: 0.997, 95% CI: 0.995-1.000; p < 0.001). CONCLUSIONS & INFERENCES: Cut-off
values for 4-s IRP defined using HREPT with solid-state catheters are not
adequate for diagnosing esophageal achalasia with water-perfused systems. A lower
value, i.e., 6.5 mmHg, is suggested for this equipment. The diagnostic criteria
of esophageal achalasia should be modified for HREPT performed with water
perfused systems.
PMID- 25124838
TI - Charles W. Vaughan, MD, 1926-2014.
PMID- 25124839
TI - Xenograft model for therapeutic drug testing in recurrent respiratory
papillomatosis.
AB - OBJECTIVE: Identifying effective treatment for papillomatosis is limited by a
lack of animal models, and there is currently no preclinical model for testing
potential therapeutic agents. We hypothesized that xenografting of papilloma may
facilitate in vivo drug testing to identify novel treatment options. METHODS: A
biopsy of fresh tracheal papilloma was xenografted into a NOD-scid
IL2Rgamma(null) (NSG) mouse. RESULTS: The xenograft began growing after 5 weeks
and was serially passaged over multiple generations. Each generation showed a
consistent log-growth pattern, and in all xenografts, the presence of the human
papillomavirus (HPV) genome was confirmed by polymerase chain reaction (PCR).
Histopathologic analysis demonstrated that the squamous architecture of the
original papilloma was maintained in each generation. In vivo drug testing with
bevacizumab (5 mg/kg i.p. twice weekly for 3 weeks) showed a dramatic therapeutic
response compared to saline control. CONCLUSION: We report here the first
successful case of serial xenografting of a tracheal papilloma in vivo with a
therapeutic response observed with drug testing. In severely immunocompromised
mice, the HPV genome and squamous differentiation of the papilloma can be
maintained for multiple generations. This is a feasible approach to identify
therapeutic agents in the treatment of recurrent respiratory papillomatosis.
PMID- 25124840
TI - Longitudinal voice outcomes following laryngeal reinnervation via vagus-to
recurrent laryngeal nerve anastomosis after vagal nerve sacrifice: a case series.
AB - OBJECTIVE: This study aimed to describe longitudinal voice outcomes of vagus-to
recurrent laryngeal nerve anastomosis following operative vagal nerve sacrifice.
METHODS: Two patients who underwent anastomosis were assessed by a
multidisciplinary voice team at 1, 4, 9, 12, and 18 months after vagal sacrifice.
RESULTS: Long-term changes in voice function based on auditory perceptual
measures of voice quality and visual perceptual changes in glottal closure were
observed and maintained for 18 months after vagus-to-recurrent laryngeal nerve
anastomosis in 2 patients with proximal vagal nerve sacrifice. Patients achieved
acceptable voice outcomes and elected not to undergo further treatment, which was
supported by Voice Handicap Index scores. CONCLUSION: Gradual restoration of
voice following operative vagal sacrifice can be achieved over an 18-month period
using vagus-to-recurrent laryngeal nerve anastomosis and warrants further
investigation in appropriately selected patients.
PMID- 25124841
TI - Facial palsy in Melkersson-Rosenthal syndrome and Bell's palsy: familial history
and recurrence tendency.
AB - OBJECTIVE: The aim of this study was to compare genetic predilection and
recurrence tendency between facial palsy in Melkersson-Rosenthal syndrome (MRS)
and Bell's palsy METHODS: We carried out an investigation on patients with facial
palsy in MRS and those with Bell's palsy who visited the outpatient department in
our hospital between February 2009 and February 2013. They were asked about
familial history and whether it was the first episode, with the results recorded
and compared. RESULTS: There were 16 patients with facial palsy in MRS and 860
patients with Bell's palsy involved in the study. Familial history was positive
in 5 of 16 patients (31.3%) with facial palsy in MRS and 56 of 860 patients
(6.5%) with Bell's palsy (P < .01). Twelve of 16 cases (75%) with facial palsy in
MRS and 88 of 860 cases (10.2%) with Bell's palsy had a history of facial palsy
in the past (P < .01). CONCLUSION: Compared to Bell's palsy, facial palsy in MRS
has an obvious genetic predilection and recurrence tendency.
PMID- 25124842
TI - Fluxionally chiral DMAP catalysts: kinetic resolution of axially chiral biaryl
compounds.
AB - Can organocatalysts that incorporate fluxional groups provide enhanced
selectivity in asymmetric transformations? To address this issue, we have
designed chiral 4-dimethylaminopyridine (DMAP) catalysts with fluxional
chirality. These catalysts were found to be efficient in promoting the acylative
kinetic resolution of secondary alcohols and axially chiral biaryl compounds with
selectivity factors of up to 37 and 51, respectively.
PMID- 25124844
TI - Evaluating degradation of silk's fibroin by attenuated total reflectance infrared
spectroscopy: case study of ancient banners from Polish collections.
AB - In this study a part of research where artificially aged model samples were used
as a guideline to the mechanism of degradation is presented. In previous work
Bombyx Mori silk samples were exposed to various environments such as different
oxygen, water vapour and volatile organic products content, all at the
temperature of 150 degrees C [11]. Based on those results gathered with by
Attenuated Total Reflectance/Fourier Transform Infrared Spectroscopy (ATR-FTIR)
the degradation estimators were proposed and classified as follows: (1) Primary
functional groups estimators EAmideI/II - intensity ratios of Amide I C=O
stretching vibration to Amide II N-H in-plane bending and C-N stretching
vibrations A1620/A1514. ECOOH - band 1318 cm(-1) integral to band integral of CH3
bending vibration band located at 1442 cm(-1)P1318/P1442. (2) Secondary
conformational estimators EcC=O2 - intensity ratios within Amide I C=O stretching
vibration of parallel beta-sheet to antiparallel beta-sheet A1620/A1699. In this
work estimators were verified against estimators calculated from spectra of silk
samples from 8 museum objects: 3 from 19th, 2 from 18th, 1 from 17th and 2 from
16th century including 3 banners from the storage resources of the Wawel Royal
Castle in Cracow, Poland.
PMID- 25124843
TI - Expression quantitative trait loci infer the regulation of isoflavone
accumulation in soybean (Glycine max L. Merr.) seed.
AB - BACKGROUND: Mapping expression quantitative trait loci (eQTL) of targeted genes
represents a powerful and widely adopted approach to identify putative regulatory
variants. Linking regulation differences to specific genes might assist in the
identification of networks and interactions. The objective of this study is to
identify eQTL underlying expression of four gene families encoding isoflavone
synthetic enzymes involved in the phenylpropanoid pathway, which are
phenylalanine ammonia-lyase (PAL; EC 4.3.1.5), chalcone synthase (CHS; EC
2.3.1.74), 2-hydroxyisoflavanone synthase (IFS; EC1.14.13.136) and flavanone 3
hydroxylase (F3H; EC 1.14.11.9). A population of 130 recombinant inbred lines
(F5:11), derived from a cross between soybean cultivar 'Zhongdou 27' (high
isoflavone) and 'Jiunong 20' (low isoflavone), and a total of 194 simple sequence
repeat (SSR) markers were used in this study. Overlapped loci of eQTLs and
phenotypic QTLs (pQTLs) were analyzed to identify the potential candidate genes
underlying the accumulation of isoflavone in soybean seed. RESULTS: Thirty three
eQTLs (thirteen cis-eQTLs and twenty trans-eQTLs) underlying the transcript
abundance of the four gene families were identified on fifteen chromosomes. The
eQTLs between Satt278-Sat_134, Sat_134-Sct_010 and Satt149-Sat_234 underlie the
expression of both IFS and CHS genes. Five eQTL intervals were overlapped with
pQTLs. A total of eleven candidate genes within the overlapped eQTL and pQTL were
identified. CONCLUSIONS: These results will be useful for the development of
marker-assisted selection to breed soybean cultivars with high or low isoflavone
contents and for map-based cloning of new isoflavone related genes.
PMID- 25124845
TI - Synthesis, characterization and biological activity of 2-acetylpyridine-alpha
naphthoxyacetylhydrazone and its metal complexes [corrected].
AB - A new series of complexes of Ni(II), Co(II), Cu(II), Cd(II), Mn(II), Hg(II) and
UO2(2+) derived from 2-acetylpyridine-alpha-naphthoxyacetylhydrazone (HA2PNA)
have been prepared and characterized by elemental analyses, spectral (IR, UV
visible, ESR and (1)H NMR) as well as magnetic and thermal measurements. The data
revealed that the ligand acts as neutral NO, NN and NNO or mono-negative NNO
chelate. On the basis of electronic spectral and magnetic moment data, an
octahedral geometry is suggested for Mn(II), Co(II), Ni(II) and UO2(2+) complexes
and a square planar arrangement for Cu(II) complex. The bond length, bond angle,
HOMO, LUMO, dipole moment and charges on the atoms have been calculated to
confirm the geometry of the ligand and the investigated complexes. The kinetic
parameters were determined for thermal degradation stages of some complexes using
Coats-Redfern and Horowitz-Metzger methods. Also, the ligand and its complexes
were screened against antibacterial, antioxidant using DPPH radical and antitumor
activities using in vitro Ehrlich ascites assay.
PMID- 25124846
TI - Synthesis, structural and vibrational investigation on 2-phenyl-N-(pyrazin-2
yl)acetamide combining XRD diffraction, FT-IR and NMR spectroscopies with DFT
calculations.
AB - The optimized molecular structure, vibrational frequencies, corresponding
vibrational assignments of 2-phenyl-N-(pyrazin-2-yl)acetamide have been
investigated experimentally and theoretically using Gaussian09 software package.
The title compound was optimized by using the HF/6-31G(6D,7F) and B3LYP/6
31G(6D,7F) calculations. The geometrical parameters are in agreement with the XRD
data. The stability of the molecule arising from hyper-conjugative interaction
and charge delocalization has been analyzed using NBO analysis. Gauge-including
atomic orbital (1)H-NMR chemical shifts calculations were carried out and
compared with experimental data. The HOMO and LUMO analysis is used to determine
the charge transfer within the molecule. Molecular electrostatic potential was
performed by the DFT method. First hyperpolarizability is calculated in order to
find its role in non linear optics. From the XRD data, in the crystal, molecules
are held together by strong C-H?O and N-H?O intermolecular interactions.
PMID- 25124847
TI - Spectroscopic properties and the catalytic activity of new organo-lead
supramolecular coordination polymer containing quinoxaline.
AB - The 3D-supramolecular coordination polymer (SCP) (3)infinity[
Cu2(CN)3(Me3Pb)(qox)], 1, as the first example of the CuCN SCP containing the
(Me3Pb) fragment, was explored to investigate its catalytic and photo-catalytic
activities. The structure of 1 contains two chemically identical but
crystallographically different [Cu2(CN)3?Me3Pb?qox]2 units with four Cu(I) sites
assuming distorted TP-3 geometry. Two non-linear chains of equal abundance are
formed producing corrugated parallel chains which are connected laterally by
quinoxaline creating 2D-layers which are arranged parallel in an (AB?AB?AB)n
fashion forming 3D-network. IR, mass, electronic absorption and fluorescence
spectra are also investigated. The SCP 1 is diamagnetic and exhibits good
catalytic and photo-catalytic activities for the degradation of methylene blue
(MB). The reaction is first order with respect to MB dye. The irradiation of the
reaction with UV-light enhanced the rate of MB mineralization. The efficiency of
recycled the 1 and the mechanism of degradation of MB dye were investigated.
PMID- 25124848
TI - SABRE is required for stabilization of root hair patterning in Arabidopsis
thaliana.
AB - Patterned differentiation of distinct cell types is essential for the development
of multicellular organisms. The root epidermis of Arabidopsis thaliana is
composed of alternating files of root hair and non-hair cells and represents a
model system for studying the control of cell-fate acquisition. Epidermal cell
fate is regulated by a network of genes that translate positional information
from the underlying cortical cell layer into a specific pattern of differentiated
cells. While much is known about the genes of this network, new players continue
to be discovered. Here we show that the SABRE (SAB) gene, known to mediate
microtubule organization, anisotropic cell growth and planar polarity, has an
effect on root epidermal hair cell patterning. Loss of SAB function results in
ectopic root hair formation and destabilizes the expression of cell fate and
differentiation markers in the root epidermis, including expression of the
WEREWOLF (WER) and GLABRA2 (GL2) genes. Double mutant analysis reveal that wer
and caprice (cpc) mutants, defective in core components of the epidermal
patterning pathway, genetically interact with sab. This suggests that SAB may act
on epidermal patterning upstream of WER and CPC. Hence, we provide evidence for a
role of SAB in root epidermal patterning by affecting cell-fate stabilization.
Our work opens the door for future studies addressing SAB-dependent functions of
the cytoskeleton during root epidermal patterning.
PMID- 25124849
TI - Non-verbal communication in meetings of psychiatrists and patients with
schizophrenia.
AB - OBJECTIVE: Recent evidence found that patients with schizophrenia display non
verbal behaviour designed to avoid social engagement during the opening moments
of their meetings with psychiatrists. This study aimed to replicate, and build
on, this finding, assessing the non-verbal behaviour of patients and
psychiatrists during meetings, exploring changes over time and its association
with patients' symptoms and the quality of the therapeutic relationship. METHOD:
40-videotaped routine out-patient consultations, involving patients with
schizophrenia, were analysed. Non-verbal behaviour of patients and psychiatrists
was assessed during three fixed, 2-min intervals using a modified Ethological
Coding System for Interviews. Symptoms, satisfaction with communication and the
quality of the therapeutic relationship were also measured. RESULTS: Over time,
patients' non-verbal behaviour remained stable, whilst psychiatrists' flight
behaviour decreased. Patients formed two groups based on their non-verbal
profiles, one group (n = 25) displaying pro-social behaviour, inviting
interaction and a second (n = 15) displaying flight behaviour, avoiding
interaction. Psychiatrists interacting with pro-social patients displayed more
pro-social behaviours (P < 0.001). Patients' pro-social profile was associated
reduced symptom severity (P < 0.05), greater satisfaction with communication (P <
0.001) and positive therapeutic relationships (P < 0.05). CONCLUSION: Patients'
non-verbal behaviour during routine psychiatric consultations remains unchanged,
and is linked to both their psychiatrist's non-verbal behaviour and the quality
of the therapeutic relationship.
PMID- 25124850
TI - An improved and validated sample cleanup method for analysis of ethyl carbamate
in Chinese liquor.
AB - Ethyl carbamate (EC) is a potential human carcinogen widely existing in fermented
foods and alcoholic beverages. The solid-phase extraction (SPE) coupled to gas
chromatography mass spectrometry is a widely-used method to determine EC levels,
but the accuracy varies with sample matrix and the effects of operation
parameters are rarely examined. In this study, the influence factors involved in
EC determination were investigated using Chinese liquor as sample matrix, and the
improved method was further applied. Three types of SPE columns, including
diatomite, Florisil, and primary-secondary amine, were compared in extraction
efficiency, and the diatomite column exhibited the highest extraction efficiency.
The optimal volumes of elution solvents with diatomite column were 15 mL for 3-mL
samples solution loaded. In addition, the alcoholic strength for EC determination
should be diluted below 20% (v/v) to avoid the enhancement of matrix-induced
chromatographic response. Moreover, the pH neutralization could help improve EC
recovery and peak resolution, reducing interfering effects. Based on these
results, the improved method showed that the limit of detection, the limit of
quantification, and average recoveries were 1.10 MUg/L, 3.65 MUg/L, and 93.06%,
respectively. To further elucidate the underlying factors related to EC
accumulation, partial least square regression analysis was conducted, and the
results suggested that EC levels had the closest relationship with alcoholic
strength among the remaining precursors.
PMID- 25124852
TI - Neurite-J: an image-J plug-in for axonal growth analysis in organotypic cultures.
AB - BACKGROUND: Previous studies in our lab proposed a method of dorsal root ganglia
(DRG) and spinal cord slice (SC) organotypic 3D cultures to study motor and
sensory axonal regeneration. Although these models are useful to test how
different factors affect axonal growth, manual sample analysis can be inaccurate
and time-consuming. Thus, we designed and set-up a plug-in to quantify axonal
growth in 3D organotypic cultures. NEW METHOD: DRG and SC were cultured in a 3D
collagen matrix. Explants were maintained in culture medium (control condition)
or in culture medium supplemented with neurotrophins. Neurites were immunolabeled
against RT-97 and pictures were obtained using an epifluorescence microscope. To
quantify axonal growth we adapted the Sholl method of concentric rings to our
cultures and the algorithm was implemented as an ImageJ plug-in. COMPARISON WITH
EXISTING METHOD(S): Our method and plug-in was compared with standard Sholl
method demonstrating better accuracy. In comparison with Neurite-J, manual
measures of axonal growth in organotypic cultures require more time and provide
fewer data than our proposed method. RESULTS: Neurite-J gives a reliable
quantitative analysis of neurite growth, providing counts of neurite number and
neurite area at different distances from the explant. Moreover, this plug-in
follows lineal and semi-logarithmic analysis of the Sholl method, yielding a
numerical value of neurite outgrowth useful for comparing different experimental
conditions. CONCLUSION: Neurite-J provides a quantification method of neurite
arbors in 3D organotypic cultures that gives the researcher an easy, fast and
reliable tool to study axonal growth.
PMID- 25124851
TI - Skull-stripping with machine learning deformable organisms.
AB - BACKGROUND: Segmentation methods for medical images may not generalize well to
new data sets or new tasks, hampering their utility. We attempt to remedy these
issues using deformable organisms to create an easily customizable segmentation
plan. We validate our framework by creating a plan to locate the brain in 3D
magnetic resonance images of the head (skull-stripping). NEW METHOD: Our method
borrows ideas from artificial life to govern a set of deformable models. We use
control processes such as sensing, proactive planning, reactive behavior, and
knowledge representation to segment an image. The image may have landmarks and
features specific to that dataset; these may be easily incorporated into the
plan. In addition, we use a machine learning method to make our segmentation more
accurate. RESULTS: Our method had the least Hausdorff distance error, but
included slightly less brain voxels (false negatives). It also had the lowest
false positive error and performed on par to skull-stripping specific method on
other metrics. COMPARISON WITH EXISTING METHOD(S): We tested our method on 838 T1
weighted images, evaluating results using distance and overlap error metrics
based on expert gold standard segmentations. We evaluated the results before and
after the learning step to quantify its benefit; we also compare our results to
three other widely used methods: BSE, BET, and the Hybrid Watershed algorithm.
CONCLUSIONS: Our framework captures diverse categories of information needed for
brain segmentation and will provide a foundation for tackling a wealth of
segmentation problems.
PMID- 25124855
TI - Sexual precocity of Nellore bulls that are offspring of super precocious,
precocious and normal cows in extensive farming conditions.
AB - The objective of this work was to verify that mothers classified as super
precocious (M1) and precocious (M2) produce more precocious bulls than females
classified as normal (M3). This study included 21,186 animals with an average age
of 21.29 +/- 1.77 months that underwent a breeding soundness evaluation from 1999
to 2008. Of these animals, 2019, 6059 and 13,108 were offspring of M1, M2 and M3
females, respectively. In the breeding soundness examination, the animals were
classified as sound for reproduction, sound under a natural mating regime,
unsound for reproduction and discarded. To compare the averages obtained for each
category of mother within the individual breeding soundness classes, a chi-square
test with a 5% error probability was used, considering the effects of year and
month of birth and farm. For the three classes of mothers (M1, M2 and M3), 67.26,
67.22 and 64.16% of bull calves were considered sound for reproduction and 19.71,
19.46 and 21.90% were considered unsound for reproduction, respectively. There
was no difference in the frequency of animals that were sound for reproduction
under the natural breeding regime between the three classes of mothers (8.87,
9.31 and 9.19%, respectively). There was a difference between the numbers of
precocious and normal females that were discarded, with frequencies of 4.01 and
4.75%, respectively (p < 0.05). There were differences in year and month of birth
and farm between super precocious and precocious cows in relation to the breeding
soundness classification of the animals. It was concluded that the bull offspring
of super precocious and precocious cows presented a higher percentage of approval
in the breeding soundness examination than the bull offspring of normal cows,
demonstrating that the selection for precocity of females has contributed to an
increase in the sexual precocity of the herd in relation to the sexual maturity
of bulls.
PMID- 25124853
TI - Long noncoding RNA associated-competing endogenous RNAs in gastric cancer.
AB - Some long noncoding RNAs (lncRNAs) play important roles in the regulation of gene
expression by acting as competing endogenous RNAs (ceRNAs). However, the roles of
lncRNA associated-ceRNAs in oncogenesis are not fully understood. Here, based on
lncRNA microarray data of gastric cancer, bioinformatic algorithm miRcode and
microRNA (miRNA) targets database TarBase, we first constructed an lncRNA-miRNA
mRNA network. Then, we confirmed it by data of six types of other cancer
including head and neck squamous cell carcinoma, prostate cancer, papillary
thyroid carcinoma, pituitary gonadotrope tumors, ovarian cancer, and chronic
lymphocytic leukemia. The results showed a clear cancer-associated ceRNA network.
Eight lncRNAs (AC009499.1, GACAT1, GACAT3, H19, LINC00152, AP000288.2, FER1L4,
and RP4-620F22.3) and nine miRNAs (miR-18a-5p, miR-18b-5p, miR-19a-3p, miR-20b
5p, miR-106a-5p, miR-106b-5p, miR-31-5p, miR-139-5p, and miR-195-5p) were
involved. For instance, through its miRNA response elements (MREs) to compete for
miR-106a-5p, lncRNA-FER1L4 regulates the expression of PTEN, RB1, RUNX1, VEGFA,
CDKN1A, E2F1, HIPK3, IL-10, and PAK7. Furthermore, cellular experimental results
indicated that FER1L4-small interfering RNA (siRNA) simultaneously suppressed
FER1L4 and RB1 mRNA level. These results suggest that lncRNAs harbor MREs and
play important roles in post-transcriptional regulation in cancer.
PMID- 25124854
TI - Association of gene variants of the renin-angiotensin system with accelerated
hippocampal volume loss and cognitive decline in old age.
AB - OBJECTIVE: Genetic factors confer risk for neuropsychiatric phenotypes, but the
polygenic etiology of these phenotypes makes identification of genetic culprits
challenging. An approach to this challenge is to examine the effects of genetic
variation on relevant endophenotypes, such as hippocampal volume loss. A smaller
hippocampus is associated with gene variants of the renin-angiotensin system
(RAS), a system implicated in vascular disease. However, no studies to date have
investigated longitudinally the effects of genetic variation of RAS on the
hippocampus. METHOD: The authors examined the effects of polymorphisms of AGTR1,
the gene encoding angiotensin-II type 1 receptor of RAS, on longitudinal
hippocampal volumes of older adults. In all, 138 older adults (age >=60 years)
were followed for an average of about 4 years. The participants underwent
repeated structural MRI and comprehensive neurocognitive testing, and they were
genotyped for four AGTR1 single-nucleotide polymorphisms (SNPs) with low pairwise
linkage disequilibrium values and apolipoprotein E (APOE) genotype. RESULTS:
Genetic variants at three AGTR1 SNPs (rs2638363, rs1492103, and rs2675511) were
independently associated with accelerated hippocampal volume loss over the 4-year
follow-up period in the right but not left hemisphere. Intriguingly, these AGTR1
risk alleles also predicted worse episodic memory performance but were not
related to other cognitive measures. Two risk variants (rs2638363 and rs12721331)
interacted with the APOE4 allele to accelerate right hippocampal volume loss.
CONCLUSIONS: Risk genetic variants of the RAS may accelerate memory decline in
older adults, an effect that may be conferred by accelerated hippocampal volume
loss. Molecules involved in this system may hold promise as early therapeutic
targets for late-life neuropsychiatric disorders.
PMID- 25124856
TI - Helminths in feline coprolites up to 9000 years in the Brazilian Northeast.
AB - The identification of parasites in animal coprolites has been an important tool
to promote knowledge about parasites infecting different zoological groups in the
past. It also helps the understanding of parasites causing zoonoses, which is
especially important for animals that were part of the diet of prehistoric human
groups. Nevertheless, the study of feline coprolites is still scarce. This study
analyzed 30 feline coprolites from southeastern Piaui taken from archeological
sites used by human groups in the past. Eggs of Spirometra sp., Toxocara cati,
Spirurida, Oxyuroidea Calodium cf. hepaticum, Trichuris cf. muris, Trichuris sp.,
and other Trichuridae, Oncicola sp., and nematode larvae were found. Some of
these findings reflect the consumption of infected prey. The role of felines in
the transmission of helminthes causing zoonoses in the region is discussed.
PMID- 25124857
TI - The antimicrobial and antibiofilm activities of copper(II) complexes.
AB - Biofilm-related bacterial infections pose a significant problem, as they are
generally more tolerant to antibiotics and the immune system. Development of
novel compounds with antibiofilm activity is therefore paramount. In this study
we have analysed metal complexes of the general structure [M(IL)(AL)](2+) (where
IL represents functionalised 1,10-phenanthrolines and AL represents 1S,2S- or
1R,2R-diaminocyclohexane) and [Cu(IL)3](2+). Antimicrobial activity was tested on
a number of bacterial strains, showing that copper(II) compounds were active
against both Gram-positive and Gram-negative bacteria, albeit that activity was
generally higher for the former. The antibiofilm activity was then determined
against a clinical isolate of meticillin-resistant Staphylococcus aureus (MRSA).
Strikingly, the copper complexes tested showed significant activity against
biofilms, and were better in the removal of biofilms than vancomycin, an
antibiotic that is currently used in the treatment of MRSA infections.
PMID- 25124858
TI - Electrospun P34HB fibres: a scaffold for tissue engineering.
AB - OBJECTIVES: Amongst the fourth generation of PHAs is bio-plasticpoly3
hydroxybutyrate4-hydroxybutyrate (P34HB); it is thus appropriate to perform novel
research on its uses and applications. The main objective of this study was to
determine whether electrospun P34HB fibres would accommodate viability, growth
and differentiation of mouse adipose-derived stem cells (mASCs). MATERIALS AND
METHODS: In the present study, we looked at P34HB in two forms, electrospun P34HB
fibres and P34HB film. Morphology of electrospun P34HB fibres and P34HB film were
characterized using scanning electron microscopy, fluorescence microscopy and
confocal laser scanning microscopy, after cell seeding. Cell adhesion,
proliferation and cytotoxicity tests were conducted on both by MTT and CCK-8
assays, respectively. After being cultured with osteogenic induction, expression
of adipogenic genes Runx2, OPN and OCN, were examined by real-time PCR. RESULTS:
By scanning electron microscopy, light microscopy and confocal laser scanning
microscopy, we observed that the mASCs grew well associated with the P34HB
materials. After MTT and CCK-8 assay, we concluded that P34HB would, indeed, be a
material suitable for further cell adhesion and proliferation studies. More
importantly, we found that the P34HB matrices promoted expression of Runx2, OPN
and OCN with osteogenic induction. CONCLUSIONS: In this investigation, we can
confirm that the electrospun P34HB fibres accommodated survival, proliferation
and differentiation of mASCs, and we have been able to draw the conclusion that
fibre scaffolds produced by the electrospinning process are promising for
application of bone tissue engineering.
PMID- 25124860
TI - Interaction Between Words and Symbolic Gestures as Revealed By N400.
AB - What happens if you see a person pronouncing the word "go" after having gestured
"stop"? Differently from iconic gestures, that must necessarily be accompanied by
verbal language in order to be unambiguously understood, symbolic gestures are so
conventionalized that they can be effortlessly understood in the absence of
speech. Previous studies proposed that gesture and speech belong to a unique
communication system. From an electrophysiological perspective the N400
modulation was considered the main variable indexing the interplay between two
stimuli. However, while many studies tested this effect between iconic gestures
and speech, little is known about the capability of an emblem to modulate the
neural response to subsequently presented words. Using high-density EEG, the
present study aimed at evaluating the presence of an N400 effect and its
spatiotemporal dynamics, in terms of cortical activations, when emblems primed
the observation of words. Participants were presented with symbolic gestures
followed by a semantically congruent or incongruent verb. A N400 modulation was
detected, showing larger negativity when gesture and words were incongruent. The
source localization during N400 time window evidenced the activation of different
portions of temporal cortex according to the gesture and word congruence. Our
data provide further evidence of how the observation of an emblem influences
verbal language perception, and of how this interplay is mainly instanced by
different portions of the temporal cortex.
PMID- 25124861
TI - Stereoselective synthesis of lanthionine derivatives in aqueous solution and
their incorporation into the peptidoglycan of Escherichia coli.
AB - The three diastereoisomers-(R,R), (S,S) and meso-of lanthionine were synthesized
in aqueous solution with high diastereoselectivity (>99%). The (S) and (R)
enantiomers of two differently protected sulfamidates were opened by nucleophilic
attack of (R) or (S)-cysteine. Acidification and controlled heating liberated the
free lanthionines. Using the same chemistry, an alpha-benzyl lanthionine was also
prepared. The proposed method, which avoids the need of enrichment by
recrystallization, opens the way to the labelling of these compounds with (35)S.
Furthermore, in vivo bioincorporation into Escherichia coli W7 was studied. No
incorporation of alpha-benzyl lanthionine was observed. In contrast, meso
lanthionine can effectively replace meso-diaminopimelic acid in vivo, while in
the presence of (R,R)-lanthionine the initial increase of bacterial growth was
followed by cell lysis. In the future, meso-[(35)S]lanthionine could be used to
study the biosynthesis of peptidoglycan and its turnover in relation to cell
growth and division.
PMID- 25124859
TI - Plasticity versus specificity in RTK signalling modalities for distinct
biological outcomes in motor neurons.
AB - BACKGROUND: Multiple growth factors are known to control several aspects of
neuronal biology, consecutively acting as morphogens to diversify neuronal fates,
as guidance cues for axonal growth, and as modulators of survival or death to
regulate neuronal numbers. The multiplicity of neuronal types is permitted by the
combinatorial usage of growth factor receptors, each of which is expressed in
distinct and overlapping subsets of neurons, and by the multitasking role of
growth factor receptors, which recruit multiple signalling cascades
differentially required for distinct biological outcomes. We have explored
signalling robustness in cells where a given receptor tyrosine kinase (RTK)
elicits qualitatively distinct outcomes. As the HGF/Met system regulates several
biological responses in motor neurons (MN) during neuromuscular development, we
have investigated the signalling modalities through which the HGF/Met system
impacts on MN biology, and the degree of robustness of each of these functions,
when challenged with substitutions of signalling pathways. RESULTS: Using a set
of mouse lines carrying signalling mutations that change the Met phosphotyrosine
binding preferences, we have asked whether distinct functions of Met in several
MN subtypes require specific signalling pathways, and to which extent signalling
plasticity allows a pleiotropic system to exert distinct developmental outcomes.
The differential ability of signalling mutants to promote muscle migration versus
axonal growth allowed us to uncouple an indirect effect of HGF/Met signalling on
nerve growth through the regulation of muscle size from a direct regulation of
motor growth via the PI3 kinase (PI3K), but not Src kinase, pathway. Furthermore,
we found that HGF/Met-triggered expansion of Pea3 expression domain in the spinal
cord can be accomplished through several alternative signalling cascades,
differentially sensitive to the Pea3 dosage. Finally, we show that the regulation
of MN survival by HGF/Met can equally be achieved in vitro and in vivo by
alternative signalling cascades involving either PI3K-Akt or Src and Mek
pathways. CONCLUSIONS: Our findings distinguish MN survival and fate
specification, as RTK-triggered responses allowing substitutions of the
downstream signalling routes, from nerve growth patterning, which depends on a
selective, non-substitutable pathway.
PMID- 25124863
TI - Reliability and validity testing of automated scoring in obstructive sleep apnea
diagnosis with the Embletta X100.
AB - OBJECTIVES/HYPOTHESIS: To verify the reliability and validity of automated
scoring and compare it to that of manual scoring for diagnosing obstructive sleep
apnea using an Embletta X100 level 2 portable device. STUDY DESIGN: Retrospective
study. METHODS: A total of 116 patients with suspected obstructive sleep apnea
who had successfully received portable polysomnography with the Embletta X100
were examined. All polysomnography data were analyzed by automated and manual
methods. Manual scoring was performed according to the revised American Academy
of Sleep Medicine 2012 criteria. Automated scoring was analyzed using the
automatic algorithm, which was updated with the American Academy of Sleep
Medicine 2012 criteria. All parameters were evaluated statistically using
correlation analysis and paired t tests. RESULTS: The apnea-hypopnea index for
automated scoring and manual scoring with the Embletta X100 were moderately
correlated (r = 0.76, P < .001). However, there was poor agreement (Bland-Altman
plot, kappa = 0.34, 0.33, and 0.26; cutoff value = 5, 15, and 30), and the apnea
hypopnea index data were generally excessively underestimated based on diagnostic
agreement and disagreement criteria. Furthermore, the apnea-hypopnea index
severity (Kendall tau-b = 0.62) between automated and manual scoring lacked good
concordance. CONCLUSIONS: Automated scoring using the Embletta X100 was
statistically moderately related to the manual scoring results. However,
automated scoring tended to excessively underestimate the apnea-hypopnea index
data compared to manual scoring. Thus, manual scoring by a sleep expert is
essential for obstructive sleep apnea diagnosis with the Embletta X100. LEVEL OF
EVIDENCE: 4.
PMID- 25124864
TI - Get a Life? The Impact of the European Working Time Directive: The Case of UK
Senior Doctors.
AB - This paper seeks to identify the effect of the implementation of the European
Working Time Directive on the working hours of UK doctors. The Labour Force
Survey is used to compare the working hours of doctors with a variety of control
groups before and after the implementation of the directive. The controls include
those unconstrained by the directive and doctor counterparts working in Europe.
We use differences-in-differences and matching methods to estimate the impact of
this natural experiment, distinguishing between the anticipation and enactment of
the European Working Time Directive. We find that the legislation reduced the
hours of senior doctors by around 8 hours in total including the component
attributable to anticipation effects and allowing for (exogenously set) rising
wages. Copyright (c) 2014 John Wiley & Sons, Ltd.
PMID- 25124862
TI - Ricinine: a pyridone alkaloid from Ricinus communis that activates the Wnt
signaling pathway through casein kinase 1alpha.
AB - Wnt signaling plays important roles in proliferation, differentiation,
development of cells, and various diseases. Activity-guided fractionation of the
MeOH extract of the Ricinus communis stem led to the isolation of four compounds
(1-4). The TCF/beta-catenin transcription activities of 1 and 3 were 2.2 and 2.5
fold higher at 20 and 30MUM, respectively. Cells treated with ricinine (1) had
higher beta-catenin and lower of p-beta-catenin (ser 33, 37, 45, Thr 41) protein
levels, whereas glycogen synthase kinase 3beta (GSK3beta) and casein kinase
1alpha (CK1alpha) protein levels remained unchanged. Cells treated with
pyrvinium, an activator of CK1alpha, had lower beta-catenin levels. However, the
combined treatment of pyrvinium and 1 led to higher beta-catenin levels than
those in cells treated with pyrvinium alone, which suggested that 1 inhibited
CK1alpha activity. Furthermore, 1 increased beta-catenin protein levels in
zebrafish embryos. These results indicated that 1 activated the Wnt signaling
pathway by inhibiting CK1alpha.
PMID- 25124865
TI - Ionic liquids as novel solvents for the synthesis of sugar fatty acid ester.
AB - Sugar fatty acid esters are bio-surfactants known for their non-toxic, non-ionic,
and high biodegradability . With great emulsifying and conditioning effects,
sugar fatty acids are widely used in the food, pharmaceutical, and cosmetic
industries. Biosynthesis of sugar fatty acid esters has attracted growing
attention in recent decades. In this study, the enzymatic synthesis of sugar
fatty acid esters in ionic liquids was developed, optimized, and scaled up.
Reaction parameters affecting the conversion yield of lipase-catalyzed synthesis
of glucose laurate from glucose and vinyl laurate (i.e. temperature, vinyl
laurate/glucose molar ratio, and enzyme loads) were optimized by response surface
methodology (RSM). In addition, production was scaled up to 2.5 L, and recycling
of enzyme and ionic liquids was investigated. The results showed that under
optimal reaction conditions (66.86 degrees C, vinyl laurate/glucose molar ratio
of 7.63, enzyme load of 73.33 g/L), an experimental conversion yield of 96.4% was
obtained which is close to the optimal value predicted by RSM (97.16%). A similar
conversion yield was maintained when the reaction was carried out at 2.5 L.
Moreover, the enzymes and ionic liquids could be recycled and reused effectively
for up to 10 cycles. The results indicate the feasibility of ionic liquids as
novel solvents for the biosynthesis of sugar fatty acid esters.
PMID- 25124866
TI - Risk of ischemic stroke in primary aldosteronism patients.
AB - BACKGROUND: High aldosterone concentrations are associated with the risk of
stroke that is independent of blood pressure levels. We investigated the risk of
ischemic stroke in primary aldosteronism (PA) patients. METHODS: This
retrospective case-control study was based on the Taiwan Primary Aldosteronism
Investigation (TAIPAI) database from 2004 to 2010. The study group comprised the
patients who developed ischemic stroke after the diagnosis of PA. The PA patients
who did not develop stroke were matched according to age and sex as the control
group. A multivariate logistic regression model was performed to determine the
risk factors of ischemic stroke. RESULTS: Of 339 patients diagnosed with PA, 22
patients (6.5%) developed de novo ischemic stroke. The PA patients with stroke
suffered from a longer hypertensive period (11.0+/-6.5 vs 7.8+/-8.3, P=.007) and
a higher prevalence of proteinuria than those who did not develop stroke (40.9%
vs 12.9%, P=.002). A multivariate logistic regression model showed that PA
patients with proteinuria (HR 3.58, P=.02), preexisting coronary artery disease
(HR 11.12, P<.001) or left ventricular hypertrophy (HR 3.09, P=.047) were
associated with an increased risk of ischemic stroke. CONCLUSIONS: Proteinuria, a
medical history of coronary artery disease or left ventricular hypertrophy, was
associated with an increased risk of ischemic stroke in PA patients. Our results
suggest that a public health initiative is necessary to enhance the follow-up of
proteinuria and to manage subsequent stroke among patients with aldosteronism.
PMID- 25124867
TI - Effects of the ABCG2 and ABCB1 drug transporter polymorphisms on the
pharmacokinetics of bicalutamide in humans.
AB - BACKGROUNDS: Bicalutamide is an oral non-steroidal anti-androgen used in the
treatment of prostate cancer. Drug transporters P-glycoprotein encoded by ABCB1
and breast cancer resistance protein (BCRP) encoded by ABCG2 are involved in the
transportation of bicalutamide and its treatment failure. We evaluated the roles
of ABCB1 and ABCG2 genetic polymorphisms in the pharmacokinetics of bicalutamide
in humans. METHODS: After a single oral dose of 150mg bicalutamide was
administered, plasma concentrations of bicalutamide were measured, and
pharmacokinetic analyses were performed in 27 healthy subjects according to ABCB1
(c.1236C>T, c.2677G>T/A, and c.3435C>T) and ABCG2 (c.34G>A and c.421C>A).
RESULTS: ABCB1 polymorphisms did not affect the plasma levels of bicalutamide and
the pharmacokinetic parameters did not differ among ABCB1 genotype groups.
However, the ABCG2 c.421C>A polymorphism significantly influenced the plasma
levels and pharmacokinetics of bicalutamide gene dose-dependently. CONCLUSIONS:
The ABCB1 genetic polymorphisms did not influence the pharmacokinetics of
bicalutamide. However, ABCG2 c.421C>A significantly and gene dose-dependently
influenced its pharmacokinetics, but c.34G>A did not.
PMID- 25124868
TI - Effect of JEZTC, a synthetic compound, on proliferation and phenotype maintenance
of rabbit articular chondrocytes in vitro.
AB - Antioxidant may provide anti-arthritic effect that contributes to resolution of
inflammation. Gallic acid (GA) and its derivatives were reported to be effective
in treatment of arthritis. But GA-suppressed cell proliferation may compromise
its effect on chondro-protection. In this study, we synthesized sulfonamido-based
gallate-JEZTC and investigated its effect on rabbit articular chondrocytes
through examination of the cell proliferation, morphology, viability,
glycosaminoglycan (GAG) synthesis, and cartilage-specific gene expression.
Results showed that JEZTC could effectively promote chondrocyte growth and
enhance secretion and synthesis of cartilage extracellular matrix (ECM) by
upregulating expression levels of aggrecan, collagen II, and Sox9 genes.
Expression of collagen I which marked chondrocyte dedifferentiation was
effectively downregulated by JEZTC. In addition, hypertrophy that may lead to
chondrocyte ossification could not be detected in JEZTC groups. The results
indicated JEZTC can well preserve the phenotype of chondrocytes. Range of 2.344
to 9.375 MUg/ml is the recommended dose of JEZTC, which showed increased cell
proliferation. Especially, JEZTC of 4.688 MUg/ml showed the best performance.
This study might provide a basis for development of a novel agent for the
treatment of symptomatic chondral and osteochondral lesions.
PMID- 25124869
TI - Recellularization potential assessment of Wharton's Jelly-derived endothelial
progenitor cells using a human fetal vascular tissue model.
AB - Mesenchymal stem cells isolated from Wharton's Jelly have demonstrated an
excellent differentiation potential into the endothelial lineage. We hypothesize
that endothelial progenitor cells differentiated from Wharton's Jelly-derived
mesenchymal stem cells have the potential to repopulate a decellularized vascular
bed employed as a biological scaffold. For this purpose, we aimed at
investigating the behavior of the endothelial progenitor cells in the
decellularized matrix and their potential to repopulate decellularized human
vascular tissue. Our main objectives were to differentiate Wharton's Jelly
derived mesenchymal stem cells into endothelial progenitor cells and to obtain a
human vascular tissue slice experimental model using the umbilical cord arteries.
We employed a decellularization method using enzymatic treatment of the umbilical
cord arteries and a recellularization method with the endothelial progenitor
cells differentiated from Wharton's Jelly mesenchymal cells in a co-culture
system, in order to investigate our hypothesis. The cellular integration within
the biological scaffold was determined by using flow cytometry analysis and
confirmed by visualization of histological staining as well as fluorescence
microscopy. The morphological observations of the recellularized scaffolds
revealed the presence of endothelial progenitor cells within the decellularized
tissue slices, displaying no degradation of the scaffold's extracellular matrix.
The flow cytometry analysis revealed the presence of Wharton's Jelly-derived
endothelial progenitor cells population in the decellularized fetal blood vessel
scaffold after recellularization. In conclusion, our results have shown that an
in vitro human vascular tissue slice experimental model using decellularized
human fetal arteries is able to sustain an adequate scaffold for cellular
implants.
PMID- 25124871
TI - Improved efficiency of definitive endoderm induction from human induced
pluripotent stem cells in feeder and serum-free culture system.
AB - Improvement of methods to produce endoderm-derived cells from pluripotent stem
cells is important to realize high-efficient induction of endodermal tissues such
as pancreas and hepatocyte. Difficulties hampering such efforts include the low
efficiency of definitive endoderm cell induction and establishing appropriate
defined culture conditions to ensure a safe cell source for human
transplantation. Based on previous studies, we revised the experimental condition
of definitive endoderm induction in feeder- and serum-free culture. Our results
suggested that CHIR99021 is more effective than Wnt3A ligand in feeder- and serum
free conditions. In addition, keeping cell density low during endoderm induction
is important for the efficiency. On the other hand, we showed that overtreatment
with CHIR99021 converted the cells into BRACHYURY-expressing posterior mesoderm
cells rather than endoderm, indicating strict CHIR99021 treatment requirements
for endoderm differentiation. Nevertheless, these results should enable better
control in the production of definitive endoderm-derived cells.
PMID- 25124872
TI - Meiotic maturation of oocytes recovered from the ovaries of Indian big cats at
postmortem.
AB - In order to increase the available sources of genetic material for endangered
members of the great cat family, this study was designed to assess the meiotic
competence of oocytes recovered from postmortem ovaries of the Indian leopard,
tiger and lion. The average number of oocytes that were recovered per ovary was
11.0 +/- 5.0, 11.0 +/- 3.5 and 21.3 +/- 8.8 for tiger, lion and leopard,
respectively. The proportion of culture grade oocytes for tiger, lion and leopard
were 72.7, 78.8 and 71.9%, respectively. The culture grade oocytes were matured
in tissue culture medium 199 modified with sodium bicarbonate supplemented with
0.3% BSA (fatty acid-free) (w/v), 10 MUg/ml FSH, 6 IU/ml LH, 1 MUg/ml 17beta
estradiol, 0.36 mM pyruvate, 2.2 mM calcium lactate, 2.0 mM L-glutamine, 100
IU/ml penicillin and 0.1 mg/ml streptomycin in an incubator with 5% CO2 under
humidified air at 38.5 degrees C for 36 h. After in vitro maturation, 56.3, 53.8
and 58.7% of the tiger, lion and leopard oocytes, respectively, were matured. The
proportion of oocytes that extruded first polar body was significantly higher
when the oocytes were collected from the animals of less than 15 yr of age
compared to above 15 yr. These findings suggest that the oocytes recovered from
ovaries of tiger, lion and leopard immediately postmortem can be successfully
matured to MII stage.
PMID- 25124870
TI - Hyaluronan in aged collagen matrix increases prostate epithelial cell
proliferation.
AB - The extracellular matrix (ECM) of the prostate, which is comprised primarily of
collagen, becomes increasingly disorganized with age, a property that may
influence the development of hyperplasia and cancer. Collageous ECM extracted
from the tails of aged mice exhibits many characteristics of collagen in aged
tissues, including the prostate. When polymerized into a 3-dimensional (3D) gel,
these collagen extracts can serve as models for the study of specific cell-ECM
interactions. In the present study, we examined the behaviors of human prostatic
epithelial cell lines representing normal prostate epithelial cells (PEC), benign
prostatic hyperplasia (BPH-1), and adenocarcinoma (LNCaP) cultured in contact
with 3D gels made from collagen extracts of young and aged mice. We found that
proliferation of PEC, BPH-1, and LNCaP cells were all increased by culture on
aged collagen gels relative to young collagen gels. In examining age-associated
differences in the composition of the collagen extracts, we found that aged and
young collagen had a similar amount of several collagen-associated ECM
components, but aged collagen had a much greater content of the glycosaminoglycan
hyaluronan (HA) than young collagen. The addition of HA (of similar size and
concentration to that found in aged collagen extracts) to cells placed in young
collagen elicited significantly increased proliferation in BPH-1 cells, but not
in PEC or LNCaP cells, relative to controls not exposed to HA. Of note,
histochemical analyses of human prostatic tissues showed significantly higher
expression of HA in BPH and prostate cancer stroma relative to stroma of normal
prostate. Collectively, these results suggest that changes in ECM involving
increased levels of HA contribute to the growth of prostatic epithelium with
aging.
PMID- 25124873
TI - Repression of multiple CYP2D genes in mouse primary hepatocytes with a single
siRNA construct.
AB - The Cyp2d subfamily is the second most abun-dant subfamily of hepatic drug
metabolizing CYPs. In mice, there are nine Cyp2d members that are believed to
have redundant catalytic activity. We are testing and optimizing the ability of
one short interfering RNA (siRNA) construct to knockdown the expression of
multiple mouse Cyp2ds in primary hepatocytes. Expression of Cyp2d10, Cyp2d11,
Cyp2d22, and Cyp2d26 was observed in the primary male mouse hepatocytes. Cyp2d9,
which is male-specific and growth hormone-dependent, was not expressed in male
primary hepatocytes, potentially because of its dependence on pulsatile growth
hormone release from the anterior pituitary. Several different siRNAs at
different concentrations and with different reagents were used to knockdown Cyp2d
expression. siRNA constructs designed to repress only one construct often mildly
repressed several Cyp2d isoforms. A construct designed to knockdown every Cyp2d
isoform provided the best results, especially when incubated with transfection
reagents designed specifically for primary cell culture. Interestingly, a
construct designed to knockdown all Cyp2d isoforms, except Cyp2d10, caused a 2.5*
increase in Cyp2d10 expression, presumably because of a compensatory response.
However, while RNA expression is repressed 24 h after siRNA treatment, associated
changes in Cyp2d-mediated metabolism are tenuous. Overall, this study provides
data on the expression of murine Cyp2ds in primary cell lines, valuable
information on designing siRNAs for silencing multiple murine CYPs, and potential
pros and cons of using siRNA as a tool for repressing Cyp2d and estimating
Cyp2d's role in murine xenobiotic metabolism.
PMID- 25124874
TI - Electronic medical record adoption in Oklahoma practices: rural-urban differences
and the role of broadband availability.
AB - PURPOSE: Most recent research has not found significant differences in electronic
medical record (EMR) adoption rates between rural and urban physicians. However,
few studies have assessed rural/urban differences at a lower level--for instance,
by specialty or size of practice. Determinants of EMR adoption by physician
practices in Oklahoma are explored, including the potential role of broadband
availability (which is required for EMR interoperability). METHODS: Surveys of
2,800 unique Oklahoma physician practices in 2011 were meshed with data from the
National Broadband Map for that same year. Summary statistics from the survey
data allowed for comparison of EMR adoption rates by sub category. Logistic
regressions were used to tease out the impact of location, specialty, and
broadband availability on the EMR adoption decision. FINDINGS: Similar overall
EMR adoption rates in rural and urban practices masked significant differences
among specific subcategories. In particular, solo practices in rural areas are
much more likely to adopt EMRs than are their urban counterparts (41% vs 33%, P <
.01); rural psychiatric practices also have measurably higher adoption rates (59%
vs 25%, P < .01). Logistic regression results demonstrate that determinants of
adoption do vary between rural and urban practices. No statistical relationship
between EMR adoption and measures of broadband availability was found.
CONCLUSIONS: Measurable differences in EMR adoption rates do exist between rural
and urban practices for specific physician categories in Oklahoma. Targeted
policies may be important for increasing EMR adoption, but policy efforts
focusing solely on broadband availability for private practices are likely
misguided.
PMID- 25124876
TI - Flexible sigmoidoscopy screening reduces colorectal cancer incidence and deaths,
study shows.
PMID- 25124877
TI - Unusually severe hypophosphatemic rickets caused by a novel and complex re
arrangement of the PHEX gene.
AB - X-linked hypophosphatemia (XLH) is caused by mutations in PHEX. Several other
genetic forms of hypophosphatemia have also been described. These disorders share
variable clinical presentation ranging from mild hypophosphatemia to severe lower
extremity bowing. We report on a 43-year-old woman with short stature, painful
leg deformities, and poor dentation. Her biochemical profile showed
hypophosphatemia with renal phosphate wasting. Due to unusually severe clinical
presentation and absence of mutations in Sanger sequencing of the PHEX gene,
quantitative multiplex ligation-dependent probe amplification was performed. A
large deletion within the PHEX gene encompassing exons 8 to 11 was identified. We
generated a specific junction fragment using long-range PCR and sequenced the
junction fragment to determine the exact deletion breakpoints. We found a
heterozygous novel complex re-arrangement involving gross deletions, insertions,
and inversion of PHEX
(hg19:g.22,115,003_22,141,395del;g:22,145,536_22,150,789delinsCins22,114,640_22,1
4,698invinsA). Thus, the complex re-arrangement including a deletion of coding
exons 8 to 11 of the PHEX can be regarded as the cause of XLH in the patient
reported here. Phosphate and active vitamin D treatment was initiated with
subsequent relief in bone pain and physical improvement. This report expands the
spectrum of clinical severity underlying genetic defects in XLH and highlights
the importance of conventional medical therapy even at adult age. Furthermore,
our findings underscore the importance of search for gene deletions in patients
with suspected XLH.
PMID- 25124878
TI - Impact of the information age on residency training: communication, access to
public information, and clinical care.
AB - Access to technology in practice helps physicians manage information,
communicate, and research topics; however, those in training receive almost no
formal preparation for integrating web-based technologies into practice. One
reason for this is that many faculty-aside from junior faculty or those in recent
generations-did not grow up using Internet communication, may use it minimally,
if at all, in their own practices, and may know little about its forms and
varieties. This report presents a case to illustrate how these disparities may
play out in the supervisory situation and makes suggestions about helping
supervisors integrate technology-awareness into their teaching.
PMID- 25124879
TI - Improved Attitudes to Psychiatry: A Global Mental Health Peer-to-Peer E-Learning
Partnership.
AB - OBJECTIVE: Health links aim to strengthen healthcare systems in low and middle
income countries through mutual exchange of skills, knowledge, and experience.
However, student participation remains limited despite growing educational
emphasis upon global health. Medical students continue to report negative
attitudes to psychiatry in high-income countries, and in Somaliland, the lack of
public sector psychiatrists limits medical students' awareness of mental
healthcare. The authors describe the design, implementation, and mixed-methods
analysis of a peer-to-peer psychiatry e-learning partnership between UK and
Somaliland students arising from a global mental health link between the two
countries. METHODS: Medical students at King's College London and Hargeisa and
Amoud universities, Somaliland, were grouped into 24 pairs. Participants aimed to
complete ten fortnightly meetings to discuss psychiatry topics via the website
MedicineAfrica. Students completed initial and final evaluations including
Attitudes toward Psychiatry (ATP-30) questions, a stigma questionnaire, and brief
evaluations after each meeting. RESULTS: Quantitative findings demonstrated that
enjoyment, interest, and academic helpfulness were rated highly by students in
Somaliland and moderately by students in the UK. Somaliland students' attitudes
to psychiatry were significantly more positive post-participation, whereas UK
students' attitudes remained stable. Qualitative findings identified more gains
in factual knowledge for Somaliland students, whereas UK students reported more
cross-cultural learning. Reasons for non-completion and student-suggested
improvements emphasized the need to ensure commitment to the program by
participants. CONCLUSIONS: This partnership encouraged students to consider
global mental health outside the standard medical education environment, through
an e-learning format solely utilizing existing resources. This new approach
demonstrates potential benefits to students in contrasting locations of brief,
focused online peer-to-peer education partnerships, expanding the scope of health
links to the medical professionals of the future.
PMID- 25124881
TI - General psychiatric residents and corrections: moving forensic education beyond
the classroom.
AB - Mental illness in the criminal justice system is one of the most important and
underserved public health challenges in psychiatry today, but few general
psychiatry residency programs offer clinical education in correctional
psychiatry. Developing such rotations might seem intimidating to educational
leaders unfamiliar with the criminal justice system, but a variety of potential
solutions exist for residency programs to offer this increasingly important
clinical training.
PMID- 25124880
TI - Understanding the dynamics of change and the impact on psychiatric education.
AB - Academic departments of psychiatry are experiencing unprecedented changes that
are difficult and challenging for faculty and administrators. This article
examines the factors that influence change and the barriers to effective change.
The author reviewed the business literature on change in organizations and
examined the psychodynamic factors that mediate individual and organizational
response to change. Several business models for effective change management exist
and can be utilized by psychiatric educators. The psychodynamic models of change
are useful for understanding the psychological impact of change on organizations
and individuals. Effective management of change requires careful attention to the
goals of the organization, development of a detailed plan to implement change,
adequate resources to carry out the change, effective leadership and
communication, and contingency plans for unforeseen events. Individual and
organizational needs must also be considered. A model for dealing with change in
education is presented.
PMID- 25124875
TI - MicroRNA-145: a potent tumour suppressor that regulates multiple cellular
pathways.
AB - MicroRNAs are endogenous, small (18-25 nucleotides) non-coding RNAs, which
regulate genes expression by directly binding to the 3'-untranslated regions of
the target messenger RNAs. Emerging evidence shows that alteration of microRNAs
is involved in cancer development. MicroRNA-145 is commonly down-regulated in
many types of cancer, regulating various cellular processes, such as the cell
cycle, proliferation, apoptosis and invasion, by targeting multiple oncogenes.
This review aims to summarize the recent published literature on the role of
microRNA-145 in regulating tumourigenesis and progression, and explore its
potential for cancer diagnosis, prognosis and treatment.
PMID- 25124883
TI - No chromosome but image duplication.
PMID- 25124882
TI - Abdominal injuries in a low trauma volume hospital--a descriptive study from
northern Sweden.
AB - BACKGROUND: Abdominal injuries occur relatively infrequently during trauma, and
they rarely require surgical intervention. In this era of non-operative
management of abdominal injuries, surgeons are seldom exposed to these patients.
Consequently, surgeons may misinterpret the mechanism of injury, underestimate
symptoms and radiologic findings, and delay definite treatment. Here, we
determined the incidence, diagnosis, and treatment of traumatic abdominal
injuries at our hospital to provide a basis for identifying potential hazards in
non-operative management of patients with these injuries in a low trauma volume
hospital. METHODS: This retrospective study included prehospital and in-hospital
assessments of 110 patients that received 147 abdominal injuries from an isolated
abdominal trauma (n = 70 patients) or during multiple trauma (n = 40 patients).
Patients were primarily treated at the University Hospital of Umea from January
2000 to December 2009. RESULTS: The median New Injury Severity Score was 9
(range: 1-57) for 147 abdominal injuries. Most patients (94%) received computed
tomography (CT), but only 38% of patients with multiple trauma were diagnosed
with CT < 60 min after emergency room arrival. Penetrating trauma caused injuries
in seven patients. Solid organ injuries constituted 78% of abdominal injuries.
Non-operative management succeeded in 82 patients. Surgery was performed for 28
patients, either immediately (n = 17) as result of operative management or later
(n = 11), due to non-operative management failure; the latter mainly occurred
with hollow viscus injuries. Patients with multiple abdominal injuries, whether
associated with multiple trauma or an isolated abdominal trauma, had
significantly more non-operative failures than patients with a single abdominal
injury. One death occurred within 30 days. CONCLUSIONS: Non-operative management
of patients with abdominal injuries, except for hollow viscus injuries, was
highly successful in our low trauma volume hospital, even though surgeons receive
low exposure to these patients. However, a growing proportion of surgeons lack
experience in decision-making and performing trauma laparotomies. Quality
assurance programmes must be emphasized to ensure future competence and quality
of trauma care at low trauma volume hospitals.
PMID- 25124885
TI - The effect of the laryngeal tie-forward procedure and soft palate cautery on
nasopharyngeal diameter in horses.
AB - The laryngeal tie-forward (LTF) procedure has been shown to move the larynx
rostrally and dorsally whilst repositioning the basihyoid bone caudally and
dorsally. Other studies have shown that the position of the hyoid bones
influences the size of the nasopharynx. The effect of the LTF procedure on the
size of the nasopharynx is unknown. It was hypothesised that the LTF procedure
would result in a decrease in dorsoventral nasopharyngeal diameter. Twenty-five
thoroughbred horses which underwent LTF with or without soft palate cautery
(LTF+/-SPC) for treatment of dorsal displacement of the soft palate were included
in this study. Preoperative and postoperative lateral radiographs were used to
determine changes in laryngohyoid position and nasopharyngeal diameter. The LTF+/
SPC procedure resulted in a significant reduction (14-17 per cent) in
dorsoventral nasopharyngeal diameter (P<0.001). The LTF procedure decreases
nasopharyngeal diameter. The impact on upper respiratory tract function during
exercise remains unclear.
PMID- 25124884
TI - Qualitative and quantitative analysis of a group of volatile organic compounds in
biological samples by HS-GC/FID: application in practical cases.
AB - A simple and sensitive procedure, using n-propanol as internal standard (IS), was
developed and validated for the qualitative and quantitative analysis of a group
of 11 volatile organic substances with different physicochemical properties (1
butanol, 2-propanol, acetaldehyde, ethyl acetate, acetone, acetonitrile,
chloroform, diethyl ether, methanol, toluene and p-xylene) in whole blood, urine
and vitreous humor. Samples were prepared by dilution with an aqueous solution of
internal standard followed by Headspace Gas Chromatography with a Flame
ionization Detector (HS GC-FID) analysis. Chromatographic separation was
performed using two capillary columns with different polarities (DB-ALC2:
30m*0.320mm*1.2MUm and DB-ALC1: 30m*0.320mm*1.8MUm), thus providing a change in
the retention and elution order of volatiles. This dual column confirmation
increases the specificity, since the risk of another substance co-eluting at the
same time in both columns is very small. The method was linear from 5 to 1000mg/L
for toluene and p-xylene, 50-1000mg/L for chloroform, and 50-2000mg/L for the
remaining substances, with correlation coefficients of over 0.99 for all
compounds. The limits of detection (LOD) ranged 1 to 10mg/L, while the limits of
quantification (LOQ) ranged from 2 to 31mg/L. The intra-day precision (CV<6.4%),
intermediate precision (CV<7.0%) and accuracy (relative error +/-10%) of the
method were in conformity with the criteria normally accepted in bioanalytical
method validation. The method developed has been applied to forensic cases, with
the advantages that it uses a small sample volume and does not require any
extraction procedure as it makes use of a headspace injection technique.
PMID- 25124887
TI - Putative candidate genes for canine hypoadrenocorticism (Addison's disease) in
multiple dog breeds.
PMID- 25124886
TI - Weather and soil type affect incidence of fasciolosis in dairy cow herds.
AB - Fasciolosis caused by Fasciola hepatica is generally a subclinical infection of
dairy cows and can result in marked economic losses on Irish dairy farms. This
study investigated the exposure to F hepatica in 237 dairy cow herds, using an in
house antibody-detection ELISA applied to bulk tank milk (BTM) samples collected
in the autumn of 2012. A total of 364 BTM samples were collected from 237
different herds, with 127 farmers submitting BTM samples in two consecutive
months. Analysis of the BTM samples indicated that 67 per cent (n= 159) of the
dairy herds had been exposed to F hepatica. Rainfall, temperature and soil types
were significantly different between the exposed and non-exposed herds (P<0.05),
highlighting the role of these variables to the exposure to F hepatica. Among the
127 herds that provided two monthly milk samples, 83 herds were exposed to F
hepatica and 82 increased their F hepatica antibody levels at the later sampling
time (P<0.01).The findings of this study confirm the high prevalence of F
hepatica antibodies in Irish dairy herds and show the rise in antibody levels
during autumn. This study is the first step towards assessing the spatiotemporal
pattern of fasciolosis in dairy herds in Ireland.
PMID- 25124889
TI - Seeking a measure of clinically meaningful change in ALS.
AB - We sought to identify a method to assess 'clinically meaningful change' perceived
by patients, caregivers and clinical raters in relation to changes in ALSFRS-R
scores at three-month intervals. In this five-site study, 81 patient-caregiver
dyads were interviewed at baseline, three, and six months to assess changes in
ALSFRS-R in relation to perceived occurrence of change, its magnitude and impact.
Ratings by patients, caregivers and clinical raters were analyzed over three
month intervals within and between respondent groups. We found that patients,
clinical raters, and caregivers agreed about 80% of the time about whether change
occurred, and in what direction, on each of three visits. The perceived magnitude
of change for the four domains measured by the ALSFRS-R was correlated with
ratings of impact within respondent groups and across time. We also found
moderate associations between changes in ALSFRS-R domain scores and judgments of
symptom impact as rated by patient, caregiver and clinical rater. Independent
measures (Quality of Life, Goal Assessment Scaling) showed no consistent
correlations with ALSFRS-R change scores. In conclusion, the use of scales to
assess the perceived magnitude and impact of change corresponding with the
domains of the ALSFRS-R may be a step towards understanding of the clinical
meaning of changes in that measure.
PMID- 25124888
TI - Comparison of clinical outcomes for 40 necrotic immature permanent incisors
treated with calcium hydroxide or mineral trioxide aggregate
apexification/apexogenesis.
AB - BACKGROUND/PURPOSE: Traumatic injury often results in pulp necrosis of immature
permanent incisors in children. This study compared clinical outcomes for 40
necrotic immature permanent incisors treated with calcium hydroxide [Ca(OH)2] or
mineral trioxide aggregate (MTA) apexification/apexogenesis. METHODS: Forty
necrotic open-apex incisors from 40 children aged 6.5-10 years were divided
evenly into four groups with each group containing teeth of similar type and
similar root apex width in patients of similar age. Group 1 incisors were treated
with ultrasonic filing and MTA placement; Group 2 were treated with ultrasonic
filing and Ca(OH)2 medication; Group 3 were treated with hand filing and MTA
placement; and Group 4 were treated with hand filing and Ca(OH)2 medication.
RESULTS: Group 1 incisors needed the shortest mean duration (5.4 +/- 1.1 weeks)
for apical hard tissue barrier formation, followed by Group 3 incisors (7.8 +/-
1.8 weeks), Group 2 incisors (11.3 +/- 1.3 weeks), and Group 4 incisors (13.1 +/-
1.5 weeks). Group 1 incisors had a significantly shorter mean elongated root
length (2.1 +/- 0.2 mm) after treatment than Group 2 incisors (3.5 +/- 0.3 mm, p
< 0.001), and Group 3 incisors had a significantly shorter mean elongated root
length (2.1 +/- 0.1 mm) after treatment than Group 4 incisors (3.7 +/- 0.3 mm, p
< 0.001). CONCLUSION: Necrotic open-apex incisors treated with ultrasonic filing
plus MTA placement need the shortest mean duration for apical hard tissue barrier
formation. For elongation of apical root length, Ca(OH)2
apexification/apexogenesis is better than MTA apexification/apexogenesis,
regardless if either ultrasonic or hand filing are used.
PMID- 25124890
TI - A genomic profile of the immune response to stroke with implications for stroke
recovery.
AB - OBJECTIVES: The objectives of this study were to determine the change in gene
expression between two time points following stroke and to identify biomarkers of
stroke recovery through gene expression profiling and pathway analysis. METHODS:
Peripheral blood was collected from 34 ischemic stroke patients (confirmed by
magnetic resonance imaging) >=18 years of age, within 24 hr of symptom onset and
24-48 hr later, and from healthy controls. The Modified Rankin Scale (MRS) was
used to determine 30-day recovery. Total RNA was extracted from whole blood in
Paxgene RNA tubes, amplified, and hybridized to Illumina HumanRef-8v2 bead chips.
Gene expression was compared in a univariate manner between stroke patients at
both time points and good versus bad outcome using t-test in GeneSpring.
Inflation of Type 1 error was corrected by false discovery rate (FDR), and
Ingenuity Systems Pathway analysis (IPA) was performed. A secondary validation
cohort was recruited from a local hospital. RESULTS: Three genes were
significantly downregulated over time (LY96, IL8, and SDPR; FDR corrected p <
.05). This finding was confirmed in a validation cohort of stroke patients (n =
8). IPA revealed cytotoxic T-lymphocyte antigen 4 (CTLA4) signaling was the most
significant pathway present in the peripheral whole blood of stroke patients 24
48 hr after onset. When controlling for age and National Institutes of Health
Stroke Scale score, high baseline expression of TLR2 and TLR4 significantly
predicted worse scores on the MRS. CONCLUSION: CTLA4 signaling is a novel pathway
for the study of stroke-induced immune suppression. Markers of immune dysfunction
early after stroke may prove useful for identifying patients with increased risk
of poor recovery.
PMID- 25124891
TI - Association of androgen-deprivation therapy with excess cardiac-specific
mortality in men with prostate cancer.
AB - OBJECTIVES: To determine if androgen-deprivation therapy (ADT) is associated with
excess cardiac-specific mortality (CSM) in men with prostate cancer and no
cardiovascular comorbidity, coronary artery disease risk factors, or congestive
heart failure (CHF) or past myocardial infarction (MI). PATIENTS AND METHODS: In
all, 5077 men (median age 69.5 years) with cT1c-T3N0M0 prostate cancer were
treated with brachytherapy with or without neoadjuvant ADT (median duration 4
months) between 1997 and 2006. Fine and Gray competing risks analysis evaluated
the association of ADT with CSM, adjusting for age, year of brachytherapy, and
ADT treatment propensity score among men in groups defined by cardiac
comorbidity. RESULTS: After a median follow-up of 4.8 years, no association was
detected between ADT and CSM in men with no cardiac risk factors (1.08% at 5
years for ADT vs 1.27% at 5 years for no ADT, adjusted hazard ratio (AHR) 0.83;
95% confidence interval (CI), 0.39-1.78; P = 0.64; n = 2653) or in men with
diabetes mellitus, hypertension, or hypercholesterolaemia (2.09% vs 1.97%, AHR
1.33; 95% CI 0.70-2.53; P = 0.39; n = 2168). However, ADT was associated with
significantly increased CSM in men with CHF or MI (AHR 3.28; 95% CI 1.01-10.64; P
= 0.048; n = 256). In this subgroup, the 5-year cumulative incidence of CSM was
7.01% (95% CI 2.82-13.82%) for ADT vs 2.01% (95% CI 0.38-6.45%) for no ADT.
CONCLUSION: ADT was associated with a 5% absolute excess risk of CSM at 5 years
in men with CHF or prior MI, suggesting that administering ADT to 20 men in this
potentially vulnerable subgroup could result in one cardiac death.
PMID- 25124892
TI - Estimation of contaminant subslab concentration in petroleum vapor intrusion.
AB - In this study, the development and partial validation are presented for an
analytical approximation method for prediction of subslab contaminant
concentrations in PVI. The method involves combining an analytic approximation to
soil vapor transport with a piecewise first-order biodegradation model (together
called the Analytic Approximation Method, including Biodegradation, AAMB), the
result of which calculation provides an estimate of contaminant subslab
concentrations, independent of building operation conditions. Comparisons with
three-dimensional (3-D) simulations and another PVI screening tool, BioVapor,
show that the AAMB is suitable for application in a scenario involving a building
with an impermeable foundation surrounded by open ground surface, where the
atmosphere is regarded as the primary oxygen source. Predictions from the AAMB
can be used to determine the required vertical source-building separation, given
a subslab screening concentration, allowing identification of buildings at risk
for PVI. This equation shows that the "vertical screening distance" suggested by
U.S. EPA is sufficient in most cases, as long as the total petroleum hydrocarbon
(TPH) soil gas concentration at the vapor source does not exceed 50-100mg/L. When
the TPH soil gas concentration of the vapor source approaches a typical limit,
i.e. 400mg/L, the "vertical screening distance" required would be much greater.
PMID- 25124894
TI - Characterization of a novel intrinsic luminescent room-temperature ionic liquid
based on [P6,6,6,14 ][ANS].
AB - Intrinsically luminescent room-temperature ionic liquids (RTILs) can be prepared
by combining a luminescent anion (more common) or cation with appropriate counter
ions, rendering new luminescent soft materials. These RTILs are still new, and
many of their photochemical properties are not well known. A novel intrinsic
luminescent RTIL based on the 8-anilinonaphthalene-1-sulfonate ([ANS]) anion
combined with the trihexyltetradecylphosphonium ([P6,6,6,14 ]) cation was
prepared and characterized by spectroscopic techniques. Detailed photophysical
studies highlight the influence of the ionic liquid environment on the ANS
fluorescence, which together with rheological and (1) H NMR experiments
illustrate the effects of both the viscosity and electrostatic interactions
between the ions. This material is liquid at room temperature and possesses a
glass transition temperature (Tg ) of 230.4 K. The fluorescence is not highly
sensitive to factors such as temperature, but owing to its high viscosity,
dynamic Stokes shift measurements reveal very slow components for the IL
relaxation.
PMID- 25124893
TI - Parallel evolution of a self-signal: humans and new world monkeys independently
lost the cell surface sugar Neu5Gc.
AB - Human sialic acid biology is unusual and thought to be unique among mammals.
Humans lack a functional cytidine monophosphate-N-acetylneuraminic acid
hydroxylase (CMAH) protein and cannot synthesize the sugar Neu5Gc, an innate
mammalian signal of self. Losing this sugar changed how humans interact with some
of our deadliest pathogens: malaria, influenza, and streptococcus among others.
We show that the New World monkeys, comprising the third of all primate species,
have human-like sialic acid biology. They have lost Neu5Gc because of an
independent CMAH inactivation ~30 million years ago (mya) (compared to ~3 mya in
hominids). This parallel loss of Neu5Gc opens sialic acid biology to comparative
phylogenetic analysis and reveals an unexpected conservation priority. New World
monkeys risk infection by human pathogens that can recognize cells in the absence
of Neu5Gc. This striking molecular convergence provides a mechanism that could
explain the long-standing observation that New World monkeys are susceptible to
some human diseases that cannot be transmitted to other primates.
PMID- 25124895
TI - Molecular signals regulating translocation and toxicity of graphene oxide in the
nematode Caenorhabditis elegans.
AB - Both in vitro and in vivo studies have demonstrated the toxic effects of graphene
oxide (GO). However, the molecular basis for the translocation and toxicity of GO
is still largely unclear. In the present study, we employed an in vivo
Caenorhabditis elegans assay system to identify molecular signals involved in the
control of the translocation and toxicity of GO. We identified 7 genes whose
mutations altered both the translocation and toxicity of GO. Mutations of the hsp
16.48, gas-1, sod-2, sod-3, and aak-2 genes caused greater GO translocation into
the body and toxic effects on both primary and secondary targeted organs compared
with wild type; however, mutations of the isp-1 and clk-1 genes resulted in
significantly decreased GO translocation into the body and toxicity on both
primary and secondary targeted organs compared with wild-type. Moreover,
mutations of the hsp-16.48, gas-1, sod-2, sod-3, and aak-2 genes caused increased
intestinal permeability and prolonged mean defecation cycle length in GO-exposed
nematodes, whereas mutations of the isp-1 and clk-1 genes resulted in decreased
intestinal permeability in GO-exposed nematodes. Therefore, for the underlying
mechanism, we hypothesize that both intestinal permeability and defecation
behavior may have crucial roles in controlling the functions of the identified
molecular signals. The molecular signals may further contribute to the control of
transgenerational toxic effects of GO. Our results provide an important insight
into understanding the molecular basis for the in vivo translocation and toxicity
of GO.
PMID- 25124898
TI - [Analysis of the curative effect of ABO-incompatible liver transplantation in the
treatment in patients with acute severe liver disease].
AB - OBJECTIVE: To analyze and evaluate the clinical effect of ABO-incompatible liver
transplantation in the treatment of acute severe liver disease. METHODS: A
retrospective clinical study was conducted. The clinical data of 4 136 patients
undergoing orthotopic liver transplantation in Organ Transplantation Center of
Tianjin First Center Hospital from September 1999 to December 2013 were analyzed.
The criteria of patients enrolled were as following: model for end-stage liver
disease (MELD) score >= 20, the donor's and recipient's blood types were
different, age 18-70 years, and undergone primary non-bypass orthotopic liver
transplantation. According to the rate of compliance with the principles of blood
transfusion, the cases were divided into two groups: ABO-compatible group (ABO-C
group, n=41), ABO-incompatible group (ABO-I group, n=22). The patients in ABO-I
group received basiliximab + methylprednisolone for immune induction therapy
during operation, basiliximab + tacrolimus + mycophenolate + cortisol as
quadruple immunosuppressive regimen after operation. They also received
subcutaneous injection of low molecular heparin for anticoagulant therapy after
operation, and oral warfarin or aspirin and clopidogrel bisulfate instead after 7
days. They also received routine alprostadil after operation. The remaining
treatment was the same as that of ABO-C group. The clinical data, postoperative
complications, rejection and survival rates of two groups were statistically
analyzed. RESULTS: There were no significant differences in gender, age, MELD
score, complicated with tumor, quality of donor liver, length of cold
preservation of donor liver, duration of operation, and blood loss during
operation between ABO-C and ABO-I groups. Number of splenectomy during operation
was significantly higher in ABO-I group than that in ABO-C group (5 cases vs. 1
case, chi2 = 4.687, P=0.030). The 3-month, 6-month, 1-year, 3-year and 5-year
survival rates of ABO-C group were 89.5%, 78.3%, 72.5%, 69.1% and 61.8%,
respectively, while those of ABO-I group were 78.9%, 72.9%, 65.6%, 56.2% and
46.8%, respectively. There was no significant difference in the cumulative
survival rate between two groups (Log Rank, chi2 = 0.647, df=1, P=0.421). The
postoperative infection rate in ABO-I group was significantly higher than that of
ABO-C group [63.6% (14/22) vs. 31.7% (13/41), chi2 = 5.960, P=0.015]. There were
no significant difference in postoperative complications of biliary tract [22.7%
(5/22) vs. 12.2% (5/41), chi2 = 0.531, P=0.466], vascular complications [31.8%
(7/22) vs. 12.2% (5/41), chi2 = 2.416, P=0.120], or rejection as diagnosed by
pathology [22.7% (5/22) vs. 9.8% (4/41), chi2 = 1.051, P=0.305] between ABO-I and
ABO-C groups. CONCLUSIONS: Although ABO-incompatible liver transplantation was
followed by higher postoperative infection rate and perioperative mortality, ABO
incompatible liver transplantation can still be used to save the patient with
acute severe liver disease as there is a shortage of compatible donor at present.
PMID- 25124896
TI - P2X7 is involved in the anti-inflammation effects of levobupivacaine.
AB - BACKGROUND: We sough to elucidate whether purinergic P2X7 receptor is actively
involved in the effects of levobupivacaine on inhibiting microglia activation.
MATERIALS AND METHODS: Microglia were treated with lipopolysaccharide (LPS, 50
ng/mL), LPS plus levobupivacaine (50 MUM), or LPS plus levobupivacaine plus the
P2X7 receptor agonist Bz-ATP (100 MUM) and denoted as the LPS, LPS + Levo, and
LPS + Levo + Bz-ATP group, respectively. Microglia activation was measured by
assaying inflammatory molecules expression. Microglia activation was also
measured by assaying neuronal cell viability using coculture of microglia and
neurons, as activated microglia may cause neuron injury. We also measured the
levels of P2X7 receptor activation in microglia using ethidium uptake assay.
RESULTS: Our data confirmed the effects of levobupivacaine on inhibiting
inflammatory molecules upregulation in activated microglia, as the concentrations
of interleukin (IL)-1beta, tumor necrosis factor alpha, IL-6, and macrophage
inflammatory protein 2, of the LPS + Levo group were significantly lower than
those of the LPS group (all P < 0.05). Moreover, Bz-ATP significantly abrogated
the inhibitory effects of levobupivacaine, as concentrations of IL-1beta, tumor
necrosis factor alpha, IL-6, and macrophage inflammatory protein 2 of the LPS +
Levo + Bz-ATP group were significantly higher than those of the LPS + Levo group
(all P < 0.05). In contrast, neuronal cell viability of the LPS + Levo group was
significantly higher than those of the LPS and LPS + Levo + Bz-ATP groups (P =
0.012 and 0.002). Moreover, levels of P2X7 receptor activation of the LPS and LPS
+ Levo + Bz-ATP groups were significantly higher than that of the LPS + Levo
group (P = 0.003 and 0.006). CONCLUSIONS: P2X7 receptor is involved in the
effects of levobupivacaine on inhibiting microglial activation.
PMID- 25124897
TI - Prophylactic fasciotomy in a porcine model of extremity trauma.
AB - BACKGROUND: Extremity injury, with concomitant hemorrhagic shock, can result in
ischemia-reperfusion injury and the formation of compartment syndrome requiring
fasciotomy. As the benefit of prophylactic fasciotomy is unclear, the objective
of this study is to determine the functional recovery of an ischemic limb with
hemorrhagic shock after prophylactic fasciotomy. MATERIAL AND METHODS: Yorkshire
swine underwent 35% blood volume hemorrhage, followed by 1, 3, and 6 h of
ischemia (n = 17; 1HR, 3HR, and 6HR) via iliac artery occlusion followed by
repair and reperfusion. A second cohort (n = 18) underwent fasciotomy of the
anterior compartment of the hind limb following vascular repair (1HR-F, 3HR-F,
and 6HR-F). Compartment pressures, measures of electromyographic (EMG) recovery,
and a validated gait score (modified Tarlov) were performed throughout a 14-d
survival period. RESULTS: Increasing ischemic intervals resulted in incremental
increases in compartment pressure (P < 0.05), although the mean did not exceed 30
mm Hg. EMG studies did not show a significant improvement comparing the 3HR with
6HR groups. There was a significant improvement in the EMG studies within the 3HR
F, when compared with 6HR-F. There was a trend toward sensory improvement between
the 3HR-F and 3HR groups. However, this did not translate to a difference in
functional outcome as measured by the Tarlov gait score. CONCLUSIONS: Within this
swine model of hemorrhagic shock and hind limb ischemia, the use of prophylactic
fasciotomies did not improve functional outcome.
PMID- 25124899
TI - [Recombinant Trichinella spiralis-53000 protein alleviates liver damage due to
lipopolysaccharides via M2 macrophage activation].
AB - OBJECTIVE: To evaluate if recombinant Trichinella spiralis-53 000 protein
(rTsP53) could alleviate liver damage caused by lipopolysaccharides (LPS) via M2
macrophage activation. METHODS: Sixty male BALB/c mice were randomly divided into
LPS group, LPS + phosphate buffer saline (PBS) group and rTsP53 intervention
group by random number table, with 20 mice in each group. Intraperitoneal
injection of 15 MUg/kg LPS was performed for all the mice in the three groups
after 8 hours of fasting. The mice in LPS + PBS group were injected with PBS
after 1 hour of LPS injection. The mice in the rTsP53 intervention group were
injected with rTsP53 (5 mg/kg) after 1 hour of LPS injection. After 48 hours all
the mice were sacrificed. Peritoneal macrophages were harvested and flow
cytometry (FCM) was used to detect markers CCR7 (M1) and CD206 (M2) of
macrophages. Hepatic tissue was harvested for pathological study after
hematoxylin-eosin (HE) staining, and double staining immunofluorescence was used
to detect F4/80+ HLA-DR+ and F4/80+ CD163+. Peripheral blood serum was harvested
to detect the levels of aspartate transaminase (AST) and alanine transaminase
(ALT). RESULTS: Compared with LPS and LPS + PBS groups, survival rate of mice of
rTsP53 intervention group was significantly elevated (90% vs. 25%, 30%, both
P<0.01), and the pathological injury of the liver was significantly ameliorated,
and the hepatic structure was better preserved. The transaminase in rTsP53
intervention group was significantly lower than that of LPS and LPS + PBS groups
(ALT: 97.7 +/- 8.5 U/L vs. 181.7 +/- 19.5 U/L, 173.7 +/- 17.2 U/L; AST: 142.7 +/-
12.1 U/L vs. 235.7 +/- 9.9 U/L, 213.7 +/- 6.7 U/L, all P<0.05), FITC-CD206+
proportion of peritoneal macrophage was significantly higher [(17.75 +/- 0.30)%
vs. (1.38 +/- 0.13)%, (1.36 +/- 0.05)%, both P<0.05] while PE-CCR7(+) proportion
[(6.89 +/- 0.11)% vs. (15.30 +/- 0.64)%, (14.96 +/- 0.93)%, both P<0.05] was
significantly lower. Fluorescence intensity of macrophages with F4/80+ CD163+
double staining for liver sections was significantly increased (0.36 +/- 0.01 vs.
0.29 +/- 0.02, 0.31 +/- 0.01, both P<0.05), while there was no significant
difference in the fluorescence intensity of macrophages with F4/80+ HLA-DR+
double staining (0.30 +/- 0.01 vs. 0.30 +/- 0.02, 0.31 +/-0.01, both P>0.05).
There was no significant difference of above results between LPS group and LPS +
PBS group (all P>0.05). CONCLUSIONS: rTsP53 could ameliorate liver damage caused
by LPS and improve animal's survival via the activation of M2 macrophage.
PMID- 25124900
TI - [The value of the baseline MELD scores, MELD-Na scores and iMELD scores in short
term prognosis in hepatitis B virus related acute-on-chronic liver failure
patients].
AB - OBJECTIVE: To explore the function of the baseline model for end-stage liver
disease (MELD) scores, MELD-Na scores and iMELD scores in short-term prognosis in
the initial treatment of hepatitis B virus (HBV) related acute-on-chronic liver
failure (ACLF) patients. METHODS: 232 HBV-related ACLF patients who received
initial treatment in 302 Military Hospital of China from January 2011 to January
2013 were enrolled in this prospective clinical follow-up. The relationship
between the baseline MELD scores, MELD-Na scores, iMELD scores and clinical
outcomes were analyzed, and the value of these three models for short term
prognosis was assessed. RESULTS: Finally the 12-week clinical follow-up was
completed in 191 patients, with the completion rate of 82.33%. Eighty-five
patients died, with the fatality rate of 44.50%. Compared with the survival
group, in non-survival group, the baseline of MELD scores (26.65 +/- 7.75 vs.
21.19 +/- 5.42, t=-5.720, P=0.000), MELD-Na scores (29.16 +/- 11.35 vs. 21.72 +/-
6.33, t=-5.729, P=0.000), iMELD scores (47.19 +/- 10.96 vs. 38.02 +/- 7.01, t=
7.011, P=0.000), total bilirubin (TBil: 374.3 +/- 150.1 MUmol/L vs. 305.5 +/-
147.1 MUmol/L, t=-3.182, P=0.002), creatinine (Cr: 110.7 +/- 90.1 MUmol/L vs.
71.1 +/- 35.1 MUmol/L, t=-4.157, P=0.000) and international normalized ratio
(INR: 2.3 +/- 0.9 vs. 2.0 +/- 0.6, t=-2.754, P=0.006) were significantly
increased, but the baseline of serum Na+ (132.8 +/- 6.1 mmol/L vs. 136.7 +/- 5.1
mmol/L, t=4.861, P=0.000) was significantly lowered. It was shown by Spearman
correlation analysis that the baseline MELD scores, MELD-Na scores and iMELD
scores all had positive correlation with the short-term prognosis of patients (r
value was 0.398, 0.404, and 0.470, respectively, all P=0.000), the baseline of
serum Na+ had a negative correlation with the short-term prognosis of patients
(r=-0.365, P=0.000). It was shown by receiver operating characteristic curve (ROC
curve) that the cut-off scores of the baseline of MELD scores, MELD-Na scores and
iMELD scores were 25.07, 25.43 and 43.11 respectively, and the area under ROC
curve (AUC) of the baseline of MELD scores, MELD-Na scores and iMELD scores were
0.731, 0.735 and 0.773, respectively. The sensitivity of the three models was
55.3%, 57.7%, 63.5%, and the specificity was 84.9%, 84.0%, 84.9% respectively.
The value of the three models had no difference in short-term prognostic
prediction. According to the respective cut-off score, the three prediction
models were divided into four groups, and all of them had differences in fatality
rate on the whole (chi2 for MELD scores was 34.740, P=0.000; chi2 for MELD-Na
scores was 36.861, P=0.000; chi2 for iMELD scores was 50.127, P=0.000). The
mortality was elevated gradually as the equation scores increased. CONCLUSIONS:
The baseline of MELD scores, MELD-Na scores and iMELD scores can predict well the
short-term prognosis of the initial treatment in HBV-related ACLF patients, and
have relatively good clinical value for guiding therapy.
PMID- 25124901
TI - [Ventilator bundle treatment of acute respiratory distress syndrome and its
correlation with biomarkers of inflammation].
AB - OBJECTIVE: To observe the levels of blood soluble urokinase plasminogen activator
receptor (suPAR), receptor of advanced glycation end products (RAGE),
procalcitonin (PCT) and C-reactive protein (CRP), and to investigate the effect
of ventilator bundle (VB) on prognosis of patients with acute respiratory
distress syndrome (ARDS). METHODS: A prospective controlled study was conducted.
A total of 54 cases of ARDS patients admitted to Department of Critical Care
Medicine of the Second Hospital of Lanzhou University who received treatment of
invasive mechanical ventilation between January 2013 and December 2013 were
enrolled. All of the patients were given VB, and then divided into completely
dependent group (VB group, n=29) and non-completely dependent group (NVB group,
n=25) according to the dependence. The mechanical ventilation time, intensive
care unit (ICU) length of stay, the incidence of ventilator associated pneumonia
(VAP), the incidence of complications and 28-day mortality rate were compared
between two groups. The blood suPAR, RAGE, PCT and CRP levels before and after
treatment were determined. The correlations between oxygenation index
(PaO(2)/FiO(2)) and other variables were analyzed by Pearson correlation and
linear regression analysis. RESULTS: (1) There was no significant difference in
gender, age, acute physiology and chronic health evaluationII (APACHE II) score
and PaO(2)/FiO(2), as well as other basic state between two groups. (2) There was
no obvious difference in suPAR, RAGE, PCT and CRP levels before treatment between
two groups. The levels of above parameters were significantly decreased after
treatment. The blood suPAR and RAGE levels in VB group were significantly
decreased compared with those in NVB group [suPAR: 189.87 (135.57) ng/L vs.
309.38 (278.00) ng/L, RAGE: 2.17 (0.75) MUg/L vs. 3.17 (2.64) MUg/L, both
P<0.01]. (3) Compared with NVB group, the mechanical ventilation time, ICU length
of stay, and the incidence of VAP in VB group were significantly reduced
(mechanical ventilation time: 131.52 +/- 44.94 hours vs. 166.28 +/- 38.09 hours,
t=-3.039, P=0.004; ICU length of hospital stay: 171.14 +/- 74.25 hours vs. 210.92
+/- 54.89 hours, t=-2.208, P=0.032; incidence of VAP: 17.24% vs. 44.00%, chi2 =
4.611, P=0.041), but 28-day mortality rate (27.59% vs. 36.00%, chi2 = 0.441,
P=0.566) and rates of other related complication showed no significant difference
between VB group and NVB group. (4) Correlation analysis showed that
PaO(2)/FiO(2) was negatively correlated with age (r=-0.290, P=0.033), suPAR (r=
0.898, P=0.000), RAGE (r=-0.898, P=0.000), PCT (r=-0.486, P=0.000) and CRP (r=
0.280, P=0.040). (5) The linear regression analysis showed PaO(2)/FiO(2) and
suPAR (t=2.645, P=0.011), RAGE (t=-2.885, P=0.006), PCT (t=2.649, P=0.011) were
significantly negatively co-related. CONCLUSIONS: Blood suPAR, RAGE, PCT and CRP
levels were correlated with the severity of ARDS patients. Compliance of VB can
affect the prognosis of patients with ARDS. The high compliance of patients can
significantly decrease the levels of blood pro-inflammatory markers, shorten the
mechanical ventilation time and ICU length of stay, reduce the incidence of VAP,
and it showed a positive impact on patients' prognosis.
PMID- 25124902
TI - [The effect of calpeptin on injury and atrophy of diaphragm under mechanical
ventilation in rats].
AB - OBJECTIVE: To investigate the effect of calpeptin on diaphragmatic injury and
atrophy under controlled mechanical ventilation in rats. METHODS: A total of 24
SPF Sprague-Dawley (SD) rats were randomly divided into anesthetized control
group (CON group), 24-hour controlled mechanical ventilation group (CMV group),
and 24-hour CMV + treatment with calpeptin group (CMVC group), with 8 rats in
each group. Animals in the CON group received an intraperitoneal injection of
pentobarbital sodium without CMV and continuous infusion of pentobarbital sodium.
A small-animal ventilator was used for 24 hours in rats of CMV group. Rats of
CMVC were treated with a specific calpain inhibitor calpeptin (4 mg/kg). The drug
was injected subcutaneously 2 hours before and 8, 15 and 23 hours after
mechanical ventilation. Changes in diaphragm ultrastructure, light microscopic
picture, and myosin heavy chain (MHC) expression were observed. RESULTS: (1)
Alignment of myofilaments and normal Z-band, and the shape of mitochondria were
maintained in CON group as revealed by electron microscope. The signs of
misalignment of myofibrils, disruption of Z-band and vacuolar mitochondria were
found in CMV group, and they were obviously improved in CMVC group. The density
of muscle injury (* 10-2/MUm2) in CMV group was significantly higher than that in
control group (36.8 +/- 13.7 vs. 6.4 +/- 6.3, t=6.373, P=0.001), and that in CMVC
group was significantly lowered (17.6 +/- 9.1 vs. 36.8 +/- 13.7, t=3.694,
P=0.002).(2) In CON group, the diaphragm fibers appeared regular in cross section
without pathologic change under light microscopy. Fuzzy muscle striations,
irregular muscle fibers, centralized nuclei and swelling of capillary endothelial
cells were observed in CMV group, while pathological changes in the CMVC group
were milder significantly. (3) In CMV group, the density of MHCslow and MHCfast
was lower compared with that of CON group, and the gray value was lowered by
61.1% (t=8.138, P=0.001) and 77.1% (t=8.844, P=0.001), respectively, especially
in MHCfast. However, the gray values of MHCslow and MHCfast were increased by
1.51 folds (t=4.601, P=0.010), and 1.33 folds (t=2.859, P=0.011), respectively,
after treatment with calpeptin, and the elevation was more significantly in
MHCslow. CONCLUSIONS: Diaphragmatic injury and atrophy were found after CMV for
24 hours. Calpeptin could reverse the detrimental effects of CMV, and it
suggested that calpain plays an important role in modulating the ventilator
induced dysfunction of the diaphragm.
PMID- 25124903
TI - [Effect of unilateral lung recruitment maneuver on hemodynamics and dead space
ratio in pigs with unilateral acute respiratory distress syndrome].
AB - OBJECTIVE: To compare unilateral lung and traditional lung recruitment maneuver
(RM) in animals with unilateral acute respiratory distress syndrome (ARDS) by
implementing independent lung ventilation, and to explore the rational mechanical
ventilation strategy for unilateral lung lesions. METHODS: Healthy hybrid pigs
were used as experimental animals, and they were divided into two groups
according to random number table method (sealed concealed envelope). There were
20 pigs in each group. According to different methods of lung RM, the
conventional mechanical ventilation (i.e. implementing ventilation for both lung
by using a ventilator) was performed as control group; the individual lung
ventilation (that was, implementing ventilation for both lung individually by
using two ventilators) as independent lung ventilation group. The model of left
lung ARDS was reproduced, and the respective RM was implemented according to
respective method of the two groups. The differences in hemodynamic parameters
and dead space ratio (VD/VT) between two groups under the RM pressure of 20, 40,
60 cmH2O (1 cmH2O=0.098 kPa) were observed. RESULTS: (1) Hemodynamics parameters
changes: with the increase in RM pressure, the heart rate (HR) in control group
showed a tendency of gradual increase, and the level at 60 cmH2O was
significantly higher than that at 20 cmH2O (192.65 +/- 22.99 bpm vs. 178.20 +/-
18.25 bpm, P<0.05). Mean arterial pressure (MAP) showed a tendency of gradual
decrease, and that at 60 cmH2O was lower significantly than that at 20 cmH2O and
40 cmH2O (78.55+/-25.77 mmHg (1 mmHg=0.133 kPa) vs. 112.40 +/- 10.84 mmHg, 106.15
+/- 13.54 mmHg, both P<0.01). Cardiac output (CO) gradually lowered, and the
differences at 20, 40, 60 cmH2O were logistically significant (11.14 +/- 2.65
L/min, 9.56 +/- 2.17 L/min, 6.01 +/- 1.39 L/min, P<0.05 or P<0.01). With an
increase in RM pressure, the difference in HR, MAP, CO in independent lung
ventilation group were not significant, and the HR at 60 cmH2O was significantly
lower than that of the control group (178.20 +/- 18.26 bpm vs. 192.65 +/- 22.99
bpm, P<0.05), and MAP and CO were significantly higher than those of the control
group (MAP: 110.80 +/- 11.60 mmHg vs. 78.55 +/- 25.77 mmHg, CO: 9.68 +/- 2.08
L/min vs. 6.01 +/- 1.39 L/min, both P<0.01). (2) VD/VT changes: with an increase
in RM pressure, the oxygenation index (PaO2/FiO2) in control group showed a
tendency of gradual decrease, and the level at 60 cmH2O was significantly lower
than that at 20 cmH2O and 40 cmH2O (126.40 +/- 37.55 mmHg vs. 187.40 +/- 21.66
mmHg, 175.20 +/- 23.00 mmHg, both P<0.01). On the right side, VD/VT showed a
tendency of gradual increase, and there was statistical significance in paired
comparison among 20, 40, 60 cmH2O (0.52 +/- 0.12, 0.60 +/- 0.15, 0.72 +/- 0.12,
P<0.05 or P<0.01). There was no obvious change on the left side. Along with the
increase in RM pressure, the PaO2/FiO2 of independent lung ventilation group
showed a tendency of gradual increase, and that at 40 cmH2O and 60 cmH2O were
significantly higher than that at 20 cmH2O (244.45 +/- 53.93 mmHg, 270.05 +/-
53.42 mmHg vs. 205.65 +/- 31.33 mmHg, P<0.05 and P<0.01), and the level at 20,
40, 60 cmH2O was higher than that of the control group (205.65+/-31.33 vs. 187.40
+/- 21.66, P<0.05; 244.45 +/- 53.93 vs. 175.20 +/- 23.00, P<0.01; 270.05 +/-
53.42 vs. 126.40 +/- 37.55, P<0.01). There were no changes in VD/VT on both
sides, and VD/VT on the right side was significantly lower than that of the
control group when the inflation pressure was 20, 40, 60 cmH2O (0.38 +/- 0.14 vs.
0.52 +/- 0.12, 0.43 +/- 0.11 vs. 0.60 +/- 0.15, 0.50 +/- 0.13 vs. 0.72 +/- 0.12,
all P<0.01). CONCLUSIONS: For severe ARDS caused by single lung injury,
implementation of independent lung RM on the basis of independent lung mechanical
ventilation for individual lung was significantly superior to the traditional
lung RM for the improvement of hemodynamic parameters and VD/VT.
PMID- 25124904
TI - [The clinical value of bedside lung ultrasound in the diagnosis of chronic
obstructive pulmonary disease and cardiac pulmonary edema].
AB - OBJECTIVE: To study the diagnostic accuracy of bedside lung ultrasound
examination in chronic obstructive pulmonary disease (COPD) and cardiac pulmonary
edema. METHODS: A prospective pilot and single-blind trial was conducted. A total
of 89 patients with respiratory failure admitted to the Department of Critical
Care Medicine of Anhui Provincial Hospital from September 2012 to September 2013
were enrolled. There were 32 patients with COPD, 31 patients with cardiac
pulmonary edema, 8 patients with interstitial lung disease, 12 with lung
infection, and 6 patients with other diseases. Another group of 30 patients
without respiratory disease were enrolled as the control group. Bedside lung
ultrasound examinations were performed in all patients within 24 hours, and chest
radiograph was performed at the same time. The signs to be revealed were the "A"
lines or horizontal lines arising from the pleural line, and the comet-tail
artifact ("B" lines) arising from the lung wall interface. RESULTS: Of 89
patients, 33 patients were shown a mean of 2.94 +/- 1.87 "A" lines per case with
the bedside lung ultrasound, and 38 patients with a mean of 3.27 +/- 1.72 "B"
lines per patient. 1.94 +/- 0.96 "A" lines a case and 1.74 +/- 0.82 "B" lines a
case in control group. There were significant difference between the test group
and control group ("A"line: t=3.835, P=0.000; "B" line: t=6.540, P=0.000). Among
32 cases with COPD, 28 patients had a positive result of "A" line with a
coincidence rate of 81.2%. In the 31 patients with cardiac pulmonary edema, 25
patients presented "B" line, with a coincidence rate of 80.6%. The "A" lines or
horizontal lines arising from the pleural line showed a sensitivity of 81.30% and
a specificity of 87.70% with a positive predictive value (PPV) 78.80% and a
negative predictive value (NPV) 89.30% of in the diagnosis of COPD, and the "B"
lines showed a sensitivity of 80.60% and a specificity of 77.60% with a PPV of
65.80% and a NPV of 88.20% in the diagnosis of cardiac pulmonary edema. However,
X-ray examination showed a sensitivity of 65.50%, a specificity of 86.00%, a PPV
of 72.40% and a NPV of 81.70% in the diagnosis of COPD, and it showed a
sensitivity of 74.20%, a specificity of 69.00%, a PPV of 56.10% and a NPV of
83.30% in the diagnosis of cardiac pulmonary edema. Bedside ultrasound was highly
consistent with X-ray in diagnosis of COPD [area under receiver operating
characteristic curve (AUC): 0.833 vs. 0.816, P>0.05], but Kappa value of
ultrasound technology "A" line in the diagnosis of COPD was greater than the
value of X-ray imaging techniques (0.685 vs. 0.527). There was little diagnostic
value of ultrasound "A" line in cardiac pulmonary edema(AUC was 0.305), while the
"B" line was superior to X-ray (AUC: 0.888 vs. 0.747, P<0.001), and had a higher
Kappa value than the value of X-ray imaging techniques (0.553 vs. 0.481) in
cardiac pulmonary edema. CONCLUSIONS: We conclude that bedside ultrasound is cost
effective, easy for repeated examination, and suitable for differential diagnosis
of lung diseases. It might be useful in screening for COPD and cardiac pulmonary
edema.
PMID- 25124905
TI - [The protective effect of valproic acid on myocardium in rats with lethal scald
injury and its mechanism].
AB - OBJECTIVE: To investigate the protective effects of valproic acid (VPA) on
myocardium in rats following lethal burn injury and its mechanism. METHODS:
Seventy-eight Sprague-Dawley (SD) rats were randomly assigned to four groups:
sham-scald group (n=10), sham-scald + VPA group (n=10), scald group (n=29), and
scald + VPA group (n=29). Rats in the latter two groups were subjected to 55%
total body surface area (TBSA) third-degree burns by immersing the back of the
trunk for 15 seconds, both lower extremities for 15 seconds, and the abdomen for
8 seconds in 80 centigrade water. Sham-scald rats were immersed in 37 centigrade
water instead. Rats were then subcutaneously injected with VPA (300 mg/kg) or
normal saline as control. Blood of 5 rats in each group was with drawn from the
abdominal aorta at 6 hours after injury for measurement of plasma creatine kinase
MB (CK-MB) activities; then the rats were sacrificed and heart tissues were
harvested for the measurement of acetylated histone H3 and activated caspase-3 by
Western Blot. The remaining rats were used for 12-hour survival analysis.
RESULTS: Compared with sham-scald group, there was a significant increase in
plasma CK-MB activities (5 438.0 +/- 413.6 U/L vs. 2 881.0 +/- 324.8 U/L, P<0.05)
and activated caspase-3 protein levels in heart tissue (gray value: 1.75 +/- 0.25
vs. 1.00 +/- 0.18, P<0.05) and an significant decline in the acetylation levels
of histone H3 (gray value: 0.55 +/- 0.18 vs. 1.00 +/- 0.20, P<0.05) after major
burn injury. VPA treatment significantly reduced the plasma CK-MB activities [(4
018.0 +/- 388.3) U/L], activated caspase-3 protein levels in heart tissue (gray
value: 1.33 +/- 0.20), and raised the acetylation levels of histone H3 (gray
value: 2.20 +/- 0.23, all P<0.05). Survival analysis by Kaplan-Meier curves
showed that the survival was improved after VPA treatment, and the survival rate
was increased from 0 to 50% at 12 hours (P<0.05). CONCLUSIONS: VPA can attenuate
cardiac injury and improve survival in a rodent model of lethal burn injury.
These protective effects may be due to its inhibitory effects on histone
deacetylase and caspase-3 activation.
PMID- 25124906
TI - [Testify patient's blood electrolyte concentration a tendency to approach that of
replacement-fluid in continuous renal replacement therapy].
AB - OBJECTIVE: To prove with mathematical formula that the patient's blood
electrolyte concentration shows a tendency to approach that of replacement-fluid
after continuous renal replacement therapy (CRRT). METHODS: Electrolyte
concentration of plasma, replacement-fluid and returning fluid were compared, and
they were labeled as C(blood), C(norm), and C(return) respectively. The
"C(return)" was calculated, and the relationship among them was demonstrated with
comparison by mathematical formula. At last, according to their relationship,
plasma change towards to the replacement fluid was analyzed. RESULTS: It was
showed that "C(blood)C(return)>C(norm)", and
according the relationship, it was derive that the trend of change in "C(blood)"
after circulation for m unit time was "C(blood)1>C(blood)2>C(blood)3> ...
>C(blood)m>C(norm)" or "C(blood)1 < C(blood)2 < C(blood)3 < ... < C(blood)m <
C(norm)". The plasma electrolyte concentration would close to that of replacement
fluid infinitely with the continue of CRRT. CONCLUSIONS: With mathematical model,
it is proved that the replacement fluid electrolyte concentration is the final
target of the plasma. We must make up the replacement fluid correctly. And this
results provide the basis for CRRT treatment of electrolyte disorder.
PMID- 25124907
TI - [The clinical application of pulse indicator continuous cardiac output monitoring
in early fluid resuscitation for patients with severe acute pancreatitis].
AB - OBJECTIVE: To evaluate the therapeutic effect of early fluid resuscitation under
the guidance of pulse indicator continuous cardiac output (PiCCO) on patients
with severe acute pancreatitis (SAP). METHODS: Clinical data of 18 SAP patients
(research group), who had undergone fluid resuscitation under the guidance of
PiCCO in the Department of Critical Care Medicine of the Second Affiliated
Hospital of Anhui Medical University from October 2011 to October 2013, were
analyzed prospectively. At the same time, clinical data of 25 cases (control
group) that had undergone fluid resuscitation without the guidance of PiCCO from
January 2009 to September 2011 were collected retrospectively. The volume of
fluid and clinical data were compared between two groups. RESULTS: During the
first 6 hours, 0-24 hours, 24-48 hours, and 0-72 hours after intensive care unit
(ICU) admission, the research group received larger volume of fluid than that of
the control group (2 133 +/- 1 593 mL vs. 1 024 +/- 421 mL, t=3.337, P=0.002; 5
960 +/- 2 951 mL vs. 3 767 +/- 854 mL, t=3.531, P=0.001; 4 709 +/- 1 508 mL vs. 3
863 +/- 1 122 mL, t=2.112, P=0.031; 14 601 +/- 5 095 mL vs. 11 409 +/- 2 667 mL,
t=2.673, P=0.007). Compared with the control group, the incidence of application
of blood purification was lowered [5.56% (1/18) vs. 44.00% (11/25), chi2 = 7.688,
P=0.006], the duration of the systemic inflammatory response syndrome (SIRS) was
shortened (3.54 +/- 2.44 days vs. 5.62 +/- 3.62 days, t=2.113, P=0.041), acute
physiology and chronic health II (APACHEII) score was significantly declined at
24 hours after admission (11 +/- 4 vs. 14 +/- 5, t=2.104, P=0.042), the blood
lactic acid was decreased more significantly after 72 hours (3.10 +/- 0.55 mmol/L
vs. 2.40 +/- 1.12 mmol/L, t=2.442, P=0.019), and the length of ICU stay was
shortened (10 +/- 9 days vs. 20 +/- 10 days, t=3.371, P=0.002) in research group.
But there was no significant difference in the percentage of the use of
vasoactive drugs [16.67% (3/18) vs. 24.00% (6/25), chi2 =0.340, P=0.560], the
incidence of invasive mechanical ventilation [50.00% (9/18) vs. 52.00% (13/25),
chi2 = 0.017, P=0.897], 72-hour urea nitrogen changes (-0.33 +/- 4.71 mmol/L vs.
0.09 +/- 5.37 mmol/L, t=0.152, P=0.880), and the percentage of abdominal
infection[16.67% (3/18) vs. 16.00% (4/25), chi2 = 0.003, P=0.953] between
research group and control group. The mortality in research group was lower than
that in control group [5.56% (1/18) vs. 20.00% (5/25)] without statistical
difference (chi2 = 1.819, P=0.178). According to the 2012 Atlanta classification,
patients were re-evaluated after 48 hours fluid resuscitation. Six patients in
research group developed moderately severe acute pancreatitis, and the incidence
was significantly higher than that in control group [33.33% (6/18) vs. 8.00%
(2/25), chi2 = 4.435, P=0.034]. The time of mean PiCCO installation was 4.5 days
in 18 cases of the research group, and no related complications occurred.
CONCLUSIONS: The PiCCO device may be a useful adjunct for fluid resuscitation
monitoring in patients with SAP within 72 hours. Early fluid resuscitation under
the guidance of PiCCO may be helpful in improving tissue perfusion, reducing the
application of blood purification, as well as shortening length of ICU stay. This
program did not increase the risk of invasive mechanical ventilation, and no
obvious change in mortality rate was observed.
PMID- 25124908
TI - [The effects of fluid resuscitation on oxygenation index and prognosis in early
stage of severe acute pancreatitis].
AB - OBJECTIVE: To analyze the correlation between fluid equilibrium and oxygen index
in patients at early stage (within 2 weeks) of severe acute pancreatitis (SAP),
and to discuss the effects of fluid equilibrium after resuscitation on the
prognosis. METHODS: A clinical study was conducted. Ninety-seven patients with
SAP admitted into Shengjing Hospital of China Medical University directly or
transferred into intensive care unit (ICU) in 24 hours after admission between
March 2011 to October 2013 were studied. Finally, 65 patients were enrolled in
statistical analysis, and those with termination of treatment prematurely were
excluded. The patients received treatment protocol formulated by the same
physician in ICU. Patients were divided into improved group and death group
according to the outcome. The differences in fluid equilibrium on 1, 2, 3, 7, 14
days after admission of ICU between the two groups were compared. The correlation
between fluid equilibrium and oxygen index was analyzed with curve fitting.
RESULTS: Among 65 patients enrolled, 53 of them were improved after intensive
care and were transferred into ordinary wards. However, 12 patients died in ICU.
Patients in the improved group showed delayed positive fluid equilibrium, and
some patients even showed negative fluid equilibrium. Patients in death group
needed more fluid to achieve fluid equilibrium. There was a significant
difference in the need of fluid to reach an equilibrium between improved group
and death group [1 day: 1 814.5 (905.2, 2 152.8) mL vs. 3 891.0 (2 524.2, 5
714.5) mL, Z=-3.303, P=0.001; 2 days: 2 469.0 (1 456.0, 3 696.0) mL vs. 6 498.0
(4 617.8, 8 763.5) mL, Z=-4.431, P<0.001; 3 days: 3 234.0 (1 098.0, 4 295.5) mL
vs. 9 533.5 (6 748.8, 10 689.0) mL, Z=-4.684, P<0.001; 7 days: 3 234.0 (1 033.0,
5 162.0) mL vs. 13 986.5 (8 045.8, 14 518.0) mL, Z=-4.718, P<0.001; 14 days: 3
234.0 (978.5, 4 924.0) mL vs. 13 436.5 (8 045.8, 14 518.0) mL, Z=-4.769,
P<0.001]. There was no correlation between fluid equilibrium and oxygen index in
improved patients within 3 days of ICU admission (R2 = 0.000, P=0.827), and it
fit the logistic curve in a relatively low level after 3 days of ICU admission
(R2 = 0.036, P<0.001). CONCLUSIONS: Early fluid resuscitation could help maintain
hemodynamics stability in SAP patients. Those SAP patients who showed a negative
equilibrium in early stage showed a better prognosis, and the fluid equilibrium
and oxygen index in improved patients fit the logistic curve after 3 days of ICU
admission.
PMID- 25124909
TI - [Comparison of the performance of three prehospital trauma scores in evaluation
of injury severity among Lushan earthquake victims].
AB - OBJECTIVE: To investigate the performance of revised trauma score (RTS), CRAMS
score (circulation, respiration, abdomen, motor and speech) and prehospital index
(PHI) on evaluation of injury severity in earthquake victims. METHODS: Data of
victims admitted to West China Hospital of Sichuan University during the Lushan
earthquake from April 20th, 2013, to April 27th were retrospectively analyzed.
The clinical information at admission was recorded, and the injury severity score
(ISS), RTS, CRAMS and PHI were calculated. The optimal cut-off values were looked
for, the comparability between the three scores and ISS score were figured out by
receiver operator characteristic curve (ROC curve), and the correlation between
ISS and three scores was analyzed by linear regression analysis. RESULTS: There
was a total of 263 victims included in the study. ISS >= 16 was found in 86
cases, and ISS<16 in 177 victims, and there were significant statistic
differences in male ratio (67.4% vs. 50.8%, chi2 = 6.477, P=0.011), RTS score
[7.55 (0.29) vs. 7.84 (0), U=6 825, P=0.013] and CRAMS scores [8 (1) vs. 9 (1),
U=3 977, P=0.000] between two groups. It was showed by ROC curve analysis that
the area under the ROC curve (AUC) of RTS, CRAMS and PHI was 0.547 (P=0.220),
0.734 (P=0.000) and 0.544 (P=0.250), and the Youden indexes of the three scores
were 0.093, 0.443, and 0.119, respectively. Moreover, the best cut-off values of
them were 4.9, 9.5 and 3.5. Linear regression analysis showed that RTS and CRAMS
score showed negative correlation with ISS score (r1=-0.139, P1=0.024; r2=-0.413,
P2=0.000), while PHI showed no relationship with it (r=0.071, P=0.250).
CONCLUSIONS: Of these three scoring systems, CRAMS has the best correlation with
ISS, and it can be used in the prompt assessment of trauma severity in earthquake
victims.
PMID- 25124910
TI - [Effect of Sheshang capsule on platelet function of rabbits bitten by
Trimeresurus stejnegeri and its mechanism].
AB - OBJECTIVE: To investigate the effect of the Sheshang capsule on coagulation of
the rabbits bitten by Trimeresurus stejnegeri and its mechanism. METHODS: The
changes in platelet aggregation rate was observed after the establishment of
rabbits model by subcutaneously injection with 0.75, 1.50, 2.25, and 3.00 mL/kg
of Trimeresurus stejnegeri venom for 72 hours. Fifty New Zealand white rabbits
were randomly divided into five groups, 10 rabbits in each group. Rabbit model
was reproduced by subcutaneously injection with 0.75 mL/kg of Trimeresurus
stejnegeri venom. The rabbits in sham group were injected with 0.75 mL/kg normal
saline(NS). The rabbits were gavaged with 5, 10, 15 mL * kg-1 * d-1 of the
Sheshang concoction to the low, intermediate and high dose groups respectively
after 6 hours, and 10 mL * kg-1 * d-1 NS was fed in the sham group and model
group. The platelet aggregation rate, platelet count (PLT), mean platelet volume
(MPV), plateletcrit (PCT), platelet distribution width (PDW), cyclic adenosine
monophosphate (cAMP) and protein kinase A (PKA) were determined after 1 week.
RESULTS: (1) With the increase in the concentration of Trimeresurus stejnegeri
venom, 1-min, 3-min, 5-min and maximum platelet aggregation rates showed a
gradual declining trends. (2) Compared with the sham group, 5-min and maximum
platelet aggregation rate in the model group were significantly decreased [35.5
(24.2, 42.5)% vs. 43.0 (38.2, 58.5)%, 39.5 (29.0, 45.0)% vs. 46.5 (39.2, 60.2)%,
both P<0.05]. Compared with the model group, 5-min and maximum platelet
aggregation rate in the intermediate dose group were significantly increased
[44.0 (39.8, 45.0) % vs. 35.5 (24.2, 42.5) %, 45.5 (43.5, 46.2) % vs. 39.5 (29.0,
45.0) %, both P<0.05]. There was no significant difference in platelet
aggregation rate among the other groups. Compared with the sham group, PLT count
in model group was obviously reduced (410.3 +/- 155.3 * 109/L vs. 724.5 +/- 220.7
* 109/L, P<0.01), so as MPV and PCT done [MPV: 5.11 +/- 1.09 fl vs. 6.34 +/- 1.16
fl, P<0.01; PCT: 21.9 (18.6, 26.8) % vs. 34.8 (24.8, 45.4) %, P<0.05]. Compared
with the model group, PLT and PCT in the low, intermediate and high dose groups
were significantly increased [PLT: 702.4 +/- 166.3 * 109/L, 648.5 +/- 160.2 *
109/L, 789.3 +/- 86.2 * 109/L vs. 410.3 +/- 155.3 * 109/L, PCT: 38.8 (35.7,
42.9)%, 36.0 (29.8, 44.4)%, 43.1 (40.5, 48.8)% vs. 21.9 (18.6, 26.8)%, all
P<0.01], and MPV in the intermediate dose group was significantly increased (6.26
+/- 1.05 fl vs. 5.11 +/- 1.09 fl, P<0.01). There was no significant difference in
PDW among groups (P>0.05). Compared with the sham group, cAMP (47.57 +/- 12.76
nmol/L vs. 36.67 +/- 10.54 nmol/L) and PKA (14.68 +/- 5.80 MUg/L vs. 9.23 +/-
4.05 MUg/L) in the model group were significantly increased (both P<0.05).
Compared with the model group, cAMP and PKA of each dose group were decreased,
while cAMP in low dose group [(36.33 +/- 11.08) nmol/L] and PKA in the
intermediate dose group [(10.21 +/- 5.31) MUg/L] were significant decreased (both
P<0.05). CONCLUSIONS: In the range of experimental concentration (0-3 mL/kg), the
higher the concentration, and the stronger the inhibition of platelet aggregation
rate was. The Sheshang capsule can raise platelet aggregation rate and PLT,
increase MPV and PCT, and act against inhibition of platelet aggregation effect
of the venom, thus improve the haemostatic function of platelet. Sheshang capsule
can be used to treat the coagulopathy induced by Trimeresurus stejnegeri venom
through regulating cAMP/PKA pathways.
PMID- 25124911
TI - [Effects of hypertonic sodium chloride hydroxyethyl starch solution on cerebral
vasospasm following subarachnoid hemorrhage and its mechanism].
AB - OBJECTIVE: To investigate the protective effect and potential mechanisms of
hypertonic sodium chloride hydroxyethyl starch solution (HSH) against the
cerebral vasospasm (CVS) following subarachnoid hemorrhage (SAH). METHODS: Twenty
four male Sprague-Dawley (SD) rats were randomly assigned to four groups
according to the random number table, with 6 rats in each group. The SAH-CVS
model was reproduced by injection of the blood twice through the cisterna magna.
Rats in both model and HSH treatment groups received 8 mL/kg normal saline (NS)
or HSH treatment everyday via caudal vein. Rats in sham group were injected with
1.5 mL/kg NS into cisterna magna followed by 8 mL/kg NS treatment. Rats in normal
group received no treatment. Rats were sacrificed to harvest basilar artery after
7 days. The thickness of vessel wall and lumen area were measured using
hematoxylin-eosin (HE) staining. The rate of apoptosis of vascular smooth muscle
cell (VSMC) was assessed using flow cytometry. Caspase-3 activity was measured by
a fluorometric assay. The expressions of Bax and Bcl-2 were determined by Western
Blot. Intracellular reactive oxygen species (ROS) was detected by H2DCFDA.
RESULTS: Compared with normal group, increased thickness of vessel wall (27.72 +/
1.94 MUm vs. 18.30 +/- 1.10 MUm, P<0.05), decreased lumen area (26 115 +/- 1 991
MUm2 vs. 55 080 +/- 2 091 MUm2, P<0.05), and elevation of rate of apoptosis of
VSMCs [(35.05 +/- 5.54) % vs. (5.93 +/- 1.53) %, P<0.05] were found in model
group. Compared with model group, decreased thickness of vessel wall (22.55 +/-
1.50 MUm vs. 27.72 +/- 1.94 MUm, P<0.05), increase of lumen area (48 115 +/- 2
460 MUm2 vs. 26 115 +/- 1 991 MUm2, P<0.05), and depressed rate of apoptosis of
VSMCs [(16.54 +/- 5.94) % vs. (35.05 +/- 5.54) %, P<0.05] were found in HSH
treatment group. Caspase-3 activity, intracellular ROS level, Bax and Bcl-2
expressions in model group were (188.40 +/- 19.35)%, (163.50 +/- 17.02)%, (208.71
+/- 26.04)% and (44.52 +/- 9.61) % of those of normal group, and the differences
of these parameters between model and normal groups were statistically
significant (all P<0.05). Caspase-3 activity, intracellular ROS level, Bax and
Bcl-2 expressions in HSH treatment group were (135.05 +/- 19.52)%, (119.44 +/-
11.50)%, (139.20 +/- 18.04)% and (85.35 +/- 13.12)% of those of normal group,
respectively, and the differences of these parameters between HSH treatment and
model groups were statistically significant (all P<0.05). The differences of all
measurements between sham and normal groups were not statistically significant.
CONCLUSIONS: The current results demonstrate that HSH attenuates the SAH-induced
CVS, alleviates thickness of vessel wall, and increases lumen area via inhibition
of VSMCs apoptosis.
PMID- 25124912
TI - [The change in auditory evoked potentials of brainstem in patients with skull
base fracture and hypoacusia].
PMID- 25124913
TI - [Diagnosis and treatment of a patient with serous Q-fever, a case report].
PMID- 25124914
TI - [Analysis of 2 cases of pulmonary embolism].
PMID- 25124915
TI - [Application of dexmedetomidine sedation in treatment of continuous state of
asthma, a case report].
PMID- 25124916
TI - [Nuclear factor-KappaB pathway and acute lung injury in hemorrhagic shock].
PMID- 25124917
TI - [An experience of the clinical features and treatment patients of the acute snake
bite around Shaanxi Guanzhong area].
PMID- 25124918
TI - [Glycocalyx and fluid management in patients with sepsis].
PMID- 25124919
TI - [Value of lung ultrasonography in the diagnosis of acute respiratory distress
syndrome].
PMID- 25124920
TI - The independent association of plateletcrit with long-term outcomes in patients
undergoing primary percutaneous coronary intervention.
AB - PURPOSE: Platelets play a key role in the genesis of thrombosis. Plateletcrit
(PCT) provides complete information on total platelet mass. The relationship
between PCT values and long-term outcomes in patients with ST-segment elevation
myocardial infarction (STEMI) who undergo primary angioplasty is not known. We
sought to determine the effect of PCT values on the outcomes of primary
angioplasty for STEMI. METHODS: Overall, 2572 consecutive STEMI patients (mean
age, 56.6+/-11.8 years) undergoing primary percutaneous coronary intervention
were enrolled retrospectively into the present study. Plateletcrit at admission
was measured as part of the automated complete blood count. Patients were
classified into 2 groups: high PCT (>0.237, n=852) and nonhigh PCT (<0.237,
n=1720). Clinical characteristics and in-hospital and long-term (median, 21
months) outcomes of primary angioplasty were analyzed. RESULTS: A higher in
hospital shock rate was observed among patients with high PCT values compared
with those with nonhigh PCT values (6.5 vs 3.8%, respectively; P=.003). The long
term cardiovascular prognosis was worse for patients with high PCT values (Kaplan
Meier, log-rank test; P=.007). We used Cox proportional hazard models to examine
the association between PCT and adverse clinical outcomes. High PCT values were
also an independent predictor of cardiovascular mortality (hazard ratio, 1.85;
95% confidence interval, 1.061-3.22; P=.03). CONCLUSION: High PCT values on
admission are independently associated with long-term adverse outcomes in
patients with STEMI who undergo primary angioplasty.
PMID- 25124922
TI - Thoracic pedicle classification determined by inner cortical width of pedicles on
computed tomography images: its clinical significance for posterior vertebral
column resection to treat rigid and severe spinal deformities-a retrospective
review of cases.
AB - BACKGROUND: Posterior vertebral column resection (PVCR) is an effective
alternative for treating rigid and severe spinal deformities. Accurate placement
of pedicle screws, especially apically, is crucial. As morphologic evaluations of
thoracic pedicles have not provided objective criteria, we propose a thoracic
pedicle classification for treating rigid and severe spinal deformities. METHODS:
A consecutive series of 56 patients with severe and rigid spinal deformities who
underwent PVCR at a single institution were reviewed retrospectively. Altogether,
1098 screws were inserted into thoracic pedicles at T2-T12. Based on the inner
cortical width of the thoracic pedicles, the patients were divided into four
groups: group 1 (0-1.0 mm), group 2 (1.1-2.0 mm), group 3 (2.1-3.0 mm), group 4
(>=3.1 mm). The proportion of screws accurately inserted in thoracic pedicles for
each group was calculated. Statistical analysis was also performed regarding
types of thoracic pedicles classified by Lenke et al. (SPINE 35:1836-1842, 2010)
using a morphological method. RESULTS: There were statistically significant
differences in the rates of screws inserted in thoracic pedicles between the
groups (P < 0.008) except groups 3 and 4 (P > 0.008), which were then combined.
The accuracies for the three new groups were 35.05%, 65.34%, and 88.32%,
respectively, with statistically significant differences between the groups (P <
0.017). Rates of screws inserted in thoracic pedicles classified by Lenke et al.
(SPINE 35:1836-1842, 2010) were 82.31%, 83.40%, 80.00%, and 30.28% for types A,
B, C, and D, respectively. There was no statistically significant difference (P >
0.008) between these types except between type D and the other three types (P <
0.008). CONCLUSIONS: The inner cortical width of thoracic pedicles is the sole
factor crucial for accurate placement of thoracic pedicle screws. We propose a
computed tomography-based classification of the pedicle's inner cortical width:
type I thoracic pedicle: absent channel, inner cortical width of 0-1 mm; type II:
presence of a channel of which type IIa has an inner cortical width of 1.1-2.0 mm
and type IIb a width of >=2.1 mm. The proposed classification can help surgeons
predict whether screws can be inserted into the thoracic pedicle, thus guiding
instrumentation when PVCR is performed.
PMID- 25124921
TI - Glutathione peroxidase's reaction intermediate selenenic acid is stabilized by
the protein microenvironment.
AB - Selenenic acids are highly reactive intermediates of selenoproteins' enzymatic
reactions. Knowledge of how the protein environment protects and stabilizes them
is fundamental not only to descriptions of selenoproteins' reactivity but also
potentially for proteomics and therapeutics. However, selenenic acids are
considered particularly short-lived and are not yet identified in wild-type
selenoproteins. Here, we report trapping the selenenic acid in glutathione
peroxidase, an antioxidant enzyme that efficiently eliminates hydroperoxides. It
has long been thought that selenium-containing glutathione peroxidases form a
selenenic acid intermediate. However, this putative species has eluded detection.
Here, we report its identification. The selenenic acid in bovine glutathione
peroxidase 1 was chemically trapped using dimedone, an alkylating agent specific
to sulfenic and selenenic acids. The alkylation of the catalytic selenocysteine
was verified by electrospray ionization mass spectrometry. In the presence of
glutathione, the selenocysteine was not alkylated because the selenenic acid
condenses faster with glutathione than the alkylation reaction. In the absence of
thiols, the selenenic acid was surprisingly long-lived with 95% of the protein
still able to react with dimedone 10 min after hydrogen peroxide was removed,
indicating that the protein environment stabilizes the selenenic acid by
shielding it from reactive groups in the protein. After 30 min, the
selenocysteine was no longer modified but became accessible once the protein was
exposed to reducing agents. This suggests that the selenenic acid reacted with a
protein's amide or amine to form a selenylamide bond. Such a modification may
play a role in protecting glutathione peroxidase'' reactivity.
PMID- 25124923
TI - Small metastasizing choroidal melanomas.
AB - PURPOSE: Small choroidal melanomas have a better prognosis than large tumours.
However, these small tumours can spread, often late in their course. The aim of
the study was to analyse survival and tumour characteristics of six cases of late
metastatic diseases after conservative treatment. METHODS: A retrospective study
was conducted at the Croix-Rousse University Hospital of Lyon among 523 patients
treated between 1991 and 2010 by proton beam therapy (508) or brachytherapy with
106 (Ru/Rh) (15) for uveal melanomas. We have selected patients with small
choroidal melanoma (thickness<=3 mm and diameter<=9 mm) (59 patients), who have
developed hepatic metastases (six of 59). RESULTS: At the time of diagnosis,
median age was 57 years (range, 37-82 years). The mean tumour thickness was 2.9
mm (range 2.5-3 mm), and the mean diameter was 7 mm (5-8 mm). Orange pigment was
observed in four cases, subretinal fluid was observed in two cases, and one
tumour touched the optic disc. Five patients had proton beam therapy. One patient
had beta brachytherapy (106 Ru/106 Rh). Average follow-up was 8.3 years (range
4.2-11.8 years). None of the six patients developed local tumour recurrence. The
mean survival time after diagnosis of melanoma was 9.8 years (range, 4.9-14.6
years). The average time from treatment of primary tumour to detection of liver
metastasis was 7 years (range 3.9-12 years). The mean survival time from the
diagnosis of metastasis was 35.2 months (range 9-101 months). Small melanoma
related death was 0% at 3 years, 1.7% at 5 years, 5.1% at 10 years and 10.2% at
15 years in our series. CONCLUSIONS: Despite a small tumoral size and an early
and effective local treatment, six of 59 small choroidal melanomas have developed
metastasis after local treatment. Small tumours represent a significant risk of
metastasis.
PMID- 25124924
TI - Prolyl isomerase Pin1 in cancer.
AB - Proline-directed phosphorylation is a posttranslational modification that is
instrumental in regulating signaling from the plasma membrane to the nucleus, and
its dysregulation contributes to cancer development. Protein interacting with
never in mitosis A1 (Pin1), which is overexpressed in many types of cancer,
isomerizes specific phosphorylated Ser/Thr-Pro bonds in many substrate proteins,
including glycolytic enzyme, protein kinases, protein phosphatases,
methyltransferase, lipid kinase, ubiquitin E3 ligase, DNA endonuclease, RNA
polymerase, and transcription activators and regulators. This Pin1-mediated
isomerization alters the structures and activities of these proteins, thereby
regulating cell metabolism, cell mobility, cell cycle progression, cell
proliferation, cell survival, apoptosis and tumor development.
PMID- 25124925
TI - Hydrogen peroxide primes heart regeneration with a derepression mechanism.
AB - While the adult human heart has very limited regenerative potential, the adult
zebrafish heart can fully regenerate after 20% ventricular resection. Although
previous reports suggest that developmental signaling pathways such as FGF and
PDGF are reused in adult heart regeneration, the underlying intracellular
mechanisms remain largely unknown. Here we show that H2O2 acts as a novel
epicardial and myocardial signal to prime the heart for regeneration in adult
zebrafish. Live imaging of intact hearts revealed highly localized H2O2 (~30 MUM)
production in the epicardium and adjacent compact myocardium at the resection
site. Decreasing H2O2 formation with the Duox inhibitors diphenyleneiodonium
(DPI) or apocynin, or scavenging H2O2 by catalase overexpression markedly
impaired cardiac regeneration while exogenous H2O2 rescued the inhibitory effects
of DPI on cardiac regeneration, indicating that H2O2 is an essential and
sufficient signal in this process. Mechanistically, elevated H2O2 destabilized
the redox-sensitive phosphatase Dusp6 and hence increased the phosphorylation of
Erk1/2. The Dusp6 inhibitor BCI achieved similar pro-regenerative effects while
transgenic overexpression of dusp6 impaired cardiac regeneration. H2O2 plays a
dual role in recruiting immune cells and promoting heart regeneration through two
relatively independent pathways. We conclude that H2O2 potentially generated from
Duox/Nox2 promotes heart regeneration in zebrafish by unleashing MAP kinase
signaling through a derepression mechanism involving Dusp6.
PMID- 25124928
TI - Domestic incense burning and nasopharyngeal carcinoma: a case-control study in
Hong Kong Chinese.
AB - Incense burning is a powerful producer of carcinogens and has been considered as
a risk factor for nasopharyngeal carcinoma (NPC). We conducted a case-control
study and case-only analyses to investigate the effect of incense burning and its
interaction with genetic background on NPC risk among Hong Kong Chinese. Between
June 2010 and December 2012, we recruited 352 incident cases of NPC and 410
controls. We collected information on lifelong practice of domestic incense
burning via interviews and genotyped 80 single nucleotide polymorphisms (SNPs) in
DNA repair genes. We observed an increased NPC risk associated with daily burning
in women [Adjusted OR = 2.49, 95% confidence interval (CI): 1.33, 4.66] but not
in men. The adjusted OR for daily burning with poor ventilation was 2.08 (95% CI:
1.02, 4.24), while that with good ventilation was 1.35 (95% CI: 0.92, 1.98).
Interactions between 2 SNPs (rs2074517 and rs4771436) and incense burning were
significantly associated with NPC risk and tended to have a SNP exposure-response
effect. Evidence for gene-environment interactions supported the knowledge that
NPC is a multi-factorial disease resulting from the joint effects of
environmental exposures and inherited susceptibility.
PMID- 25124926
TI - Arginase I, polyamine, and prostaglandin E2 pathways suppress the inflammatory
response and contribute to diffuse cutaneous leishmaniasis.
AB - Diffuse cutaneous leishmaniasis (DCL) is a rare clinical manifestation of
tegumentary leishmaniasis. The molecular mechanisms underlying DCL pathogenesis
remain unclear, and there is no efficient treatment available. This study
investigated the systemic and in situ expression of the inflammatory response
that might contribute to suppression in DCL. The plasma levels of arginase I,
ornithine decarboxylase (ODC), transforming growth factor beta (TGF-beta), and
prostaglandin E2 (PGE2) were higher in patients with DCL, compared with patients
with localized cutaneous leishmaniasis (LCL) or with controls from an area of
endemicity. In situ transcriptomic analyses reinforced the association between
arginase I expression and enzymes involved in prostaglandin and polyamine
synthesis. Immunohistochemistry confirmed that arginase I, ODC, and
cyclooxygenase2 expression was higher in lesion biopsy specimens from patients
with DCL than in those from patients with LCL. Inhibition of arginase I or ODC
abrogates L. amazonensis replication in infected human macrophages. Our data
implicate arginase I, ODC, PGE2, and TGF-beta in the failure to mount an
efficient immune response and suggest perspectives in the development of new
strategies for therapeutic intervention for patients with DCL.
PMID- 25124927
TI - Characterization of drug-resistant influenza A(H7N9) variants isolated from an
oseltamivir-treated patient in Taiwan.
AB - BACKGROUND: Patients contracting influenza A(H7N9) infection often developed
severe disease causing respiratory failure. Neuraminidase (NA) inhibitors (NAIs)
are the primary option for treatment, but information on drug-resistance markers
for influenza A(H7N9) is limited. METHODS: Four NA variants of
A/Taiwan/1/2013(H7N9) virus containing a single substitution (NA-E119V, NA-I222K,
NA-I222R, or NA-R292K) recovered from an oseltamivir-treated patient were tested
for NAI susceptibility in vitro; their replicative fitness was evaluated in cell
culture, mice, and ferrets. RESULTS: NA-R292K led to highly reduced inhibition by
oseltamivir and peramivir, while NA-E119V, NA-I222K, and NA-I222R caused reduced
inhibition by oseltamivir. Mice infected with any virus showed severe clinical
signs with high mortality rates. NA-I222K virus was the most virulent in mice,
whereas virus lacking NA change (NA-WT) and NA-R292K virus seemed the least
virulent. Sequence analysis suggests that PB2-S714N increased virulence of NA
I222K virus in mice; NS1-K126R, alone or in combination with PB2-V227M, produced
contrasting effects in NA-WT and NA-R292K viruses. In ferrets, all viruses
replicated to high titers in the upper respiratory tract but produced only mild
illness. NA-R292K virus, showed reduced replicative fitness in this animal model.
CONCLUSIONS: Our data highlight challenges in assessment of the replicative
fitness of H7N9 NA variants that emerged in NAI-treated patients.
PMID- 25124930
TI - Role of sleep duration as a risk factor for Type 2 diabetes among adults of
different ages in Japan: the Niigata Wellness Study.
AB - AIM: To compare the role of short sleep duration as a risk factor for diabetes
among adults of different ages. METHODS: The study enrolled 38987 Japanese
individuals without diabetes, and the 8-year risk of developing diabetes
attributable to different sleep durations (< 5.5 h, 5.5 to < 6.5 h, 6.5 to < 7.0
h, 7.0-7.5 h, > 7.5-8.0 h, or > 8.0 h) was assessed among individuals aged <= 45,
46-59 or >= 60 years. RESULTS: During the 8-year follow-up period, 2085
individuals developed diabetes. Overall, individuals with a short sleep duration
of < 5.5 h or 5.5 to < 6.5 h had, respectively, a 1.53-fold (95% CI 1.19, 1.97)
or 1.25-fold (95% CI 1.10, 1.42) increased risk of diabetes as compared with
those who had 7.0-7.5 h of sleep. A sleep duration of < 5.5 h or 5.5 to < 6.5 h
was predictive of the development of diabetes among individuals aged <= 45 years,
but not among those aged >= 60 years. With increasing age, the effect of short
sleep duration on the risk of diabetes was attenuated. CONCLUSIONS: Short sleep
duration was predictive of diabetes among young or middle-aged Japanese adults
but not among elderly individuals after age was considered. Managing habitual
short sleep and the possible reasons for having such short sleep duration could
be particularly important for young or middle-aged adults in the development of
future diabetes.
PMID- 25124933
TI - Diagnosis and treatment of dynamic collapse of the cricotracheal ligament in
thoroughbred racehorses.
AB - OBJECTIVE: To describe (1) diagnosis of dynamic collapse of the cricotracheal
ligament in a group of horses and (2) treatment and outcome of affected horses.
STUDY DESIGN: Retrospective case series. ANIMALS: Thoroughbred horses (n = 8).
METHODS: Of 600 over ground dynamic endoscopic examinations performed, 8
Thoroughbred horses had cricotracheal ligament collapse (CTLC); 5 were 2 years
old and in early training and 2 were mature horses in full work. CTLC was
diagnosed if circumferential collapse of the cricotracheal ligament was
identified during exercise. Seven horses had repeat endoscopic examination. Two
horses unresponsive to conservative management were treated surgically. RESULTS:
Multiple abnormalities of the upper portion of the respiratory tract were
identified along with CTLC in all five 2-year-old horses and resolution of CTLC
was observed after treatment for upper airway inflammation. No concurrent
respiratory abnormality was identified in the 2 mature horses. Surgical reduction
of the cricotracheal space and imbrication of the cricotracheal ligament of these
2 horses resulted in resolution of clinical signs of CTLC. CONCLUSIONS: CTLC is a
rare cause of dynamic obstruction in Thoroughbred racehorses. Resolution may
occur after adaptation to training and after inflammation of the respiratory
tract is resolved, but for horses with persistent CTLC, surgical reduction of the
cricotracheal space and imbrication of the cricotracheal ligament may result in
resolution of clinical signs.
PMID- 25124932
TI - Complete response of sunitinib therapy for renal cell cancer recurrence in the
native kidney after renal transplantation: a case report.
AB - BACKGROUND: No case report has yet shown that sunitinib therapy for the
postoperative recurrence of renal cancer in a native kidney after renal
transplantation can achieve complete response (CR). CASE PRESENTATION: A tumor
was detected in the right native kidney of a 35-year-old Japanese male 10 years
after renal transplantation. A tumor thrombus that reached the atrium was
detected, which suggested cT3cN0M0. Because of the risk of perioperative
complications, preoperative therapy with sunitinib was selected and 8 courses
were administered. The size of the primary tumor was reduced by 33%, while that
of the tumor thrombus was decreased by 39.5%. Right nephrectomy and removal of
the tumor thrombus were then performed. Contrast-enhanced computed tomography
(CT) four months after surgery suggested local relapse. Sunitinib was
administered for 9 months, which led to complete response (CR). CONCLUSIONS: This
study presented the case of sunitinib therapy for renal cancer in the native
kidney after renal transplantation. The therapeutic efficacy and safety for such
cases should be discussed.
PMID- 25124929
TI - Functionalized nanoscale micelles with brain targeting ability and intercellular
microenvironment biosensitivity for anti-intracranial infection applications.
AB - Due to complication factors such as blood-brain barrier (BBB), integrating high
efficiency of brain target ability with specific cargo releasing into one
nanocarrier seems more important. A brain targeting nanoscale system is developed
using dehydroascorbic acid (DHA) as targeting moiety. DHA has high affinity with
GLUT1 on BBB. More importantly, the GLUT1 transportation of DHA represents a "one
way" accumulative priority from blood into brain. The artificial micelles are
fabricated by a disulfide linkage, forming a bio-responsive inner barrier, which
can maintain micelles highly stable in circulation and shield the leakage of
entrapped drug before reaching the targeting cells. The designed micelles can
cross BBB and be further internalized by brain cells. Once within the cells, the
drug release can be triggered by high intracellular level of glutathione (GSH).
Itraconazole (ITZ) is selected as the model drug because of its poor brain
permeability and low stability in blood. It demonstrates that the functionalized
nanoscale micelles can achieve highly effective direct drug delivery to targeting
site. Based on the markedly increased stability in blood circulation and improved
brain delivery efficiency of ITZ, DHA-modified micelles show highly effective in
anti-intracranial infection. Therefore, this smart nanodevice shows a promising
application for the treatment of brain diseases.
PMID- 25124931
TI - Phenotypic overlap between familial exudative vitreoretinopathy and microcephaly,
lymphedema, and chorioretinal dysplasia caused by KIF11 mutations.
AB - IMPORTANCE: Retinal detachment with avascularity of the peripheral retina,
typically associated with familial exudative vitreoretinopathy (FEVR), can result
from mutations in KIF11, a gene recently identified to cause microcephaly,
lymphedema, and chorioretinal dysplasia (MLCRD) as well as chorioretinal
dysplasia, microcephaly, and mental retardation (CDMMR). Ophthalmologists should
be aware of the range of presentations for mutations in KIF11 because the
phenotypic distinction between FEVR and MLCRD/CDMMR portends management
implications in patients with these conditions. OBJECTIVE: To identify gene
mutations in patients who present with a FEVR phenotype and explore the spectrum
of ocular and systemic abnormalities caused by KIF11 mutations in a cohort of
patients with FEVR or microcephaly in conjunction with chorioretinopathy or FEVR.
DESIGN, SETTING, AND PARTICIPANTS: Clinical data and DNA were collected from each
participant between 1998 and 2013 from the clinical practices of ophthalmologists
and clinical geneticists internationally. Twenty-eight FEVR probands with
diagnoses made by the referring physician and without a known FEVR gene mutation,
and 3 with microcephaly and chorioretinopathy, were included. At least 1 patient
in each pedigree manifested 1 or more of the following: macular dragging, partial
retinal detachment, falciform folds, or total retinal detachment. EXPOSURES:
Whole-exome sequencing was conducted on affected members in multiplex pedigrees,
and Sanger sequencing of the 22 exons of the KIF11 gene was performed on
singletons. Clinical data and history were collected and reviewed. MAIN OUTCOMES
AND MEASURES: Identification of mutations in KIF11. RESULTS: Four novel
heterozygous KIF11 mutations and 1 previously published mutation were identified
in probands with FEVR: p.A218Gfs*15, p.E470X, p.R221G, c.790-1G>T, and the
previously described heterozygous p.R47X. Documentation of peripheral avascular
areas on intravenous fluorescein angiography was possible in 2 probands with
fibrovascular proliferation demonstrating phenotypic overlap with FEVR.
CONCLUSIONS AND RELEVANCE: Mutations in KIF11 cause a broader spectrum of ocular
disease than previously reported, including retinal detachment. The KIF11 gene
likely plays a role in retinal vascular development and mutations in this gene
can lead to clinical overlap with FEVR. Cases of FEVR should be carefully
inspected for the presence of microcephaly as a marker for KIF11-related disease
to enhance the accuracy of the prognosis and genetic counseling.
PMID- 25124934
TI - Biofilms formed by the archaeon Haloferax volcanii exhibit cellular
differentiation and social motility, and facilitate horizontal gene transfer.
AB - BACKGROUND: Archaea share a similar microbial lifestyle with bacteria, and not
surprisingly then, also exist within matrix-enclosed communities known as
biofilms. Advances in biofilm biology have been made over decades for model
bacterial species, and include characterizations of social behaviors and cellular
differentiation during biofilm development. Like bacteria, archaea impact
ecological and biogeochemical systems. However, the biology of archaeal biofilms
is only now being explored. Here, we investigated the development, composition
and dynamics of biofilms formed by the haloarchaeon Haloferax volcanii DS2.
RESULTS: Biofilms were cultured in static liquid and visualized with fluorescent
cell membrane dyes and by engineering cells to express green fluorescent protein
(GFP). Analysis by confocal scanning laser microscopy showed that H. volcanii
cells formed microcolonies within 24 h, which developed into larger clusters by
48 h and matured into flake-like towers often greater than 100 MUm in height
after 7 days. To visualize the extracellular matrix, biofilms formed by GFP
expressing cells were stained with concanavalin A, DAPI, Congo red and thioflavin
T. Stains colocalized with larger cellular structures and indicated that the
extracellular matrix may contain a combination of polysaccharides, extracellular
DNA and amyloid protein. Following a switch to biofilm growth conditions, a sub
population of cells differentiated into chains of long rods sometimes exceeding
25 MUm in length, compared to their planktonic disk-shaped morphology. Time-lapse
photography of static liquid biofilms also revealed wave-like social motility.
Finally, we quantified gene exchange between biofilm cells, and found that it was
equivalent to the mating frequency of a classic filter-based experimental method.
CONCLUSIONS: The developmental processes, functional properties and dynamics of
H. volcanii biofilms provide insight on how haloarchaeal species might persist,
interact and exchange DNA in natural communities. H. volcanii demonstrates some
biofilm phenotypes similar to bacterial biofilms, but also has interesting
phenotypes that may be unique to this organism or to this class of organisms,
including changes in cellular morphology and an unusual form of social motility.
Because H. volcanii has one of the most advanced genetic systems for any
archaeon, the phenotypes reported here may promote the study of genetic and
developmental processes in archaeal biofilms.
PMID- 25124935
TI - Inverse associations of total and decaffeinated coffee with liver enzyme levels
in National Health and Nutrition Examination Survey 1999-2010.
AB - Coffee may have hepatoprotective effects and higher coffee consumption has been
associated inversely with levels of liver enzymatic markers. However, it is
unclear whether decaffeinated coffee is also associated with liver enzymes. The
study population included 27,793 participants, age 20 or older, in the U.S.
National Health and Nutrition Examination Survey (1999-2010). Coffee intake was
evaluated by 24-hour dietary recall. Serum levels of alanine aminotransferase
(ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma
glutamyl transaminase (GGT) were measured. We examined the relationship between
coffee intake and enzymatic levels using weighted multiple variable logistic
(abnormally elevated levels of enzymes) and linear regression (continuous
enzymatic levels). Total coffee consumption was inversely associated with
abnormal levels of all four liver enzymes and continuous levels of AST, ALP, and
GGT. Compared to those reporting no coffee consumption, participants reporting >=
3 cups per day had an odds ratio (OR; 95% confidence interval [CI]) of 0.75
(0.63, 0.89), 0.82 (0.68, 0.98), 0.73 (0.55, 0.95), and 0.69 (0.57, 0.83) for
abnormal levels of ALT, AST, ALP, and GGT, respectively. Similar inverse
associations were found with decaffeinated coffee intake and abnormal levels of
ALT (OR (>= 2 vs 0 cup/d): 0.62 [0.41, 0.94]), AST (0.74 [0.49, 1.11]), and GGT
(0.70 [0.49-1.00]). CONCLUSION: Higher intakes of coffee, regardless of its
caffeine content, were associated with lower levels of liver enzymes.
PMID- 25124937
TI - High-level conversion of L-lysine into 5-aminovalerate that can be used for nylon
6,5 synthesis.
AB - L-Lysine is a potential feedstock for the production of bio-based precursors for
engineering plastics. In this study, we developed a microbial process for high
level conversion of L-lysine into 5-aminovalerate (5AVA) that can be used as a
monomer in nylon 6,5 synthesis. Recombinant Escherichia coli WL3110 strain
expressing Pseudomonas putida delta-aminovaleramidase (DavA) and lysine 2
monooxygenase (DavB) was grown to high density in fed-batch culture and used as a
whole cell catalyst. High-density E. coli WL3110 expressing DavAB, grown to an
optical density at 600 nm (OD600 ) of 30, yielded 36.51 g/L 5AVA from 60 g/L L
lysine in 24 h. Doubling the cell density of E. coli WL3110 improved the
conversion yield to 47.96 g/L 5AVA from 60 g/L of L-lysine in 24 h. 5AVA
production was further improved by doubling the L-lysine concentration from 60 to
120 g/L. The highest 5AVA titer (90.59 g/L; molar yield 0.942) was obtained from
120 g/L L-lysine by E. coli WL3110 cells grown to OD600 of 60. Finally, nylon 6,5
was synthesized by bulk polymerization of epsilon-caprolactam and delta
valerolactam prepared from microbially synthesized 5AVA. The hybrid system
demonstrated here has promising possibilities for application in the development
of industrial bio-nylon production processes.
PMID- 25124938
TI - Selective episiotomy vs. implementation of a non episiotomy protocol: a
randomized clinical trial.
AB - BACKGROUND: World Health Organization (WHO) recommends that the episiotomy rate
should be around 10%, which is already a reality in many European countries.
Currently the use of episiotomy should be restricted and physicians are
encouraged to use their clinical judgment to decide when the procedure is
necessary. There is no clinical evidence corroborating any indication of
episiotomy, so until the present moment it is not yet known whether episiotomy is
indeed necessary in any context of obstetric practice. OBJECTIVES: To compare
maternal and perinatal outcomes in women undergoing a protocol of not performing
episiotomy versus selective episiotomy. METHODS/DESIGN: An open label randomized
clinical trial will be conducted including laboring women with term pregnancy,
maximum dilation of 8 cm, live fetus in cephalic vertex presentation. Women with
bleeding disorders of pregnancy, indication for caesarean section and those
without capacity to consent and without legal guardians will be excluded. Primary
outcomes will be frequency of episiotomy, delivery duration, frequency of
spontaneous lacerations and perineal trauma, frequency of instrumental delivery,
postpartum blood loss, need for perineal suturing, number of sutures, Apgar
scores at one and five minutes, need for neonatal resuscitation and pH in cord
blood. As secondary outcomes frequency complications of perineal suturing,
postpartum perineal pain, maternal satisfaction, neonatal morbidity and admission
newborn in NICU will be assessed. Women will be invited to participate and those
who agree will sign the consent form and will be then assigned to a protocol of
not conducting episiotomy (experimental group) or to a group that episiotomy is
performed selectively according to the judgment of the provider of care delivery
(control Group). The present study was approved by IMIP's Research Ethics
Committee. TRIAL REGISTRATION: Clinical Trials Register under the number and was
registered in ClinicalTrials.gov under the number NCT02178111.
PMID- 25124936
TI - Antimicrobial and antibiofilm potential of biosurfactants isolated from
lactobacilli against multi-drug-resistant pathogens.
AB - BACKGROUND: Biosurfactants (BS) are amphiphilic compounds produced by microbes,
either on the cell surface or secreted extracellularly. BS exhibit strong
antimicrobial and anti-adhesive properties, making them good candidates for
applications used to combat infections. In this study, our goal was to assess the
in vitro antimicrobial, anti-adhesive and anti-biofilm abilities of BS produced
by Lactobacillus jensenii and Lactobacillus rhamnosus against clinical Multidrug
Resistant (MDR) strains of Acinetobacter baumannii, Escherichia coli, and
Staphylococcus aureus (MRSA). Cell-bound BS from both L. jensenii and L.
rhamnosus were extracted and isolated. The surface activities of crude BS samples
were evaluated using an oil spreading assay. The antimicrobial, anti-adhesive and
anti-biofilm activities of both BS against the above mentioned MDR pathogens were
determined. RESULTS: Surface activities for both BS ranged from 6.25 to 25 mg/ml
with clear zones observed between 7 and 11 cm. BS of both L. jensenii and L.
rhamnosus showed antimicrobial activities against A. baumannii, E. coli and S.
aureus at 25-50 mg/ml. Anti-adhesive and anti-biofilm activities were also
observed for the aforementioned pathogens between 25 and 50 mg/ml. Finally,
analysis by electron microscope indicated that the BS caused membrane damage for
A. baumannii and pronounced cell wall damage in S. aureus. CONCLUSION: Our
results indicate that BS isolated from two Lactobacilli strains has antibacterial
properties against MDR strains of A. baumannii, E. coli and MRSA. Both BS also
displayed anti-adhesive and anti-biofilm abilities against A. baumannii, E. coli
and S. aureus. Together, these capabilities may open up possibilities for BS as
an alternative therapeutic approach for the prevention and/or treatment of
hospital-acquired infections.
PMID- 25124939
TI - Lack of activity of betulin-based Oleogel-S10 in the treatment of actinic
keratoses: a randomized, multicentre, placebo-controlled double-blind phase II
trial.
AB - BACKGROUND: Betulinic acid and other triterpenes have shown strong antitumour
activity in vitro and in vivo. A triterpene extract of birch bark formed the base
of Oleogel-S10 and allowed topical application. Two previous trials have shown
efficacy and tolerability in the treatment of actinic keratoses (AKs) with
betulin-based Oleogel-S10. OBJECTIVES: To confirm the efficacy and
tolerability/safety of Oleogel-S10 in the treatment of AKs in a multicentre
placebo-controlled study. METHODS: Patients (n = 165) were treated topically for
3 months in a four-arm parallel study design, randomly allocated to A (n = 53)
Oleogel-S10 once daily, B (n = 51) Oleogel-S10 twice daily, or C (n = 25) or D (n
= 28) placebo (petroleum jelly) once or twice daily, respectively. Clinical
efficacy in this double-blind study was assessed by the investigators. Final and
baseline biopsies were evaluated by central histopathology. RESULTS: Complete
clearance of the target lesions was seen in 4% of patients in group A and 7% in
group B, but not in the placebo groups. A clearance rate of > 75% was seen for
15% and 18% of patients in groups A and B, respectively, and for 13% in the
placebo groups. These differences were not statistically significant.
Histopathologically, 43.9% of patients showed a downgrading or clearance of the
marker AK with no significant differences between the groups. Treatment with
Oleogel-S10 was well tolerated. The tolerability as assessed by the investigator
was mostly 'very good' (78.8%), followed by 'good' (18.2%) and only 1.2% assessed
it as 'intolerable'. Patient-assessed tolerability was graded mostly 'very good'
(56.4%) or 'good' (34.5%). CONCLUSIONS: Treatment with Oleogel-S10 was well
tolerated during a treatment period of 3 months, yet was no better than placebo
in terms of efficacy in the treatment of AKs.
PMID- 25124940
TI - Sensitivity testing of trypanosome detection by PCR from whole blood samples
using manual and automated DNA extraction methods.
AB - Automated extraction of DNA for testing of laboratory samples is an attractive
alternative to labour-intensive manual methods when higher throughput is
required. However, it is important to maintain the maximum detection sensitivity
possible to reduce the occurrence of type II errors (false negatives; failure to
detect the target when it is present), especially in the biomedical field, where
PCR is used for diagnosis. We used blood infected with known concentrations of
Trypanosoma copemani to test the impact of analysis techniques on trypanosome
detection sensitivity by PCR. We compared combinations of a manual and an
automated DNA extraction method and two different PCR primer sets to investigate
the impact of each on detection levels. Both extraction techniques and
specificity of primer sets had a significant impact on detection sensitivity.
Samples extracted using the same DNA extraction technique performed substantially
differently for each of the separate primer sets. Type I errors (false positives;
detection of the target when it is not present), produced by contaminants, were
avoided with both extraction methods. This study highlights the importance of
testing laboratory techniques with known samples to optimise accuracy of test
results.
PMID- 25124941
TI - A Fasciola hepatica-derived fatty acid binding protein induces protection against
schistosomiasis caused by Schistosoma bovis using the adjuvant adaptation (ADAD)
vaccination system.
AB - Several efforts have been made to identify anti-schistosomiasis vaccine
candidates and new vaccination systems. The fatty acid binding protein (FAPB) has
been shown to induce a high level of protection in trematode infection. The
adjuvant adaptation (ADAD) vaccination system was used in this study, including
recombinant FABP, a natural immunomodulator and saponins. Mice immunised with the
ADAD system were able to up-regulate proinflammatory cytokines (IL-1 and IL-6)
and induce high IgG2a levels. Moreover, there was a significant reduction in worm
burden, egg liver and hepatic lesion in vaccinated mice in two independent
experiments involving Schistosoma bovis infected mice. The foregoing data shows
that ADAD system using FABP provide a good alternative for triggering an
effective immune response against animal schistosomiasis.
PMID- 25124942
TI - Thermochromic luminescent nest-like silver thiolate cluster.
AB - A novel discrete open high-nuclearity nest-like silver thiolate cluster complex,
[Ag33 S3 (StBu)16 (CF3 COO)9 (NO3 )(CH3 CN)2 ](NO3 ) (1), has been isolated with
nitrate and S(2-) anions acting as structure-directing templates. Its similar
nest-like structure has been assembled into an extended layer [Ag31 S3 (StBu)16
(NO3 )9 ]n (2) by adjustment of auxiliary ligand. More interestingly, both
complexes exhibit temperature-dependent luminescence of high sensitivity with a
large fluorescence enhancement (12-fold for 1, 21-fold for 2), which can be
easily recognized by the naked-eye (dramatic red-shift Delta=104 nm for 1, larger
Delta=113 nm for 2 at 77 K compared to those at 298 K). The correlation between
luminescent thermochromism and temperature-dependent variation of the
coordination modes of template NO3 (-) anion, Ag???S and Ag???Ag distances are
also elucidated through variable-temperature single-crystal X-ray crystal
structure (VT-SCXRD) analyses.
PMID- 25124943
TI - Pro re nata prescribing in a population receiving palliative care: a prospective
consecutive case note review.
AB - OBJECTIVES: To document pro re nata (PRN) prescribing practices and to identify
patterns with respect to clinical characteristics and the medications prescribed.
DESIGN: Prospective consecutive case note review. SETTING: Two interrelated
consultative hospice and palliative care services in regional Victoria,
Australia. PARTICIPANTS: Terminally ill inpatients and community-based
individuals (N = 203) at the time of referral to a hospice or palliative care
service. MEASUREMENTS: Number of medications that the referring physician
prescribed on a PRN basis and on a regular basis for symptom control; comorbid
disease, performance status, comorbidity burden, disease phase, and survival.
RESULTS: Mean number of PRN medications prescribed was 3.0, with significantly
higher rates in the last week of life (rate ratio (RR) = 1.30, 95% confidence
interval (CI) = 1.07-1.59) and during the terminal phase of disease (RR = 1.36,
95% CI = 1.09-1.68). One-quarter of prescriptions were for medications that met
the Beers consensus criteria for potentially inappropriate medication use in
elderly persons. CONCLUSION: These descriptive baseline data are new. A mean of
three different medications allows responsiveness to a variety of fluctuating
symptoms, but there was a large range within the sample, indicating that some
individuals and their caregivers have a high burden of administration-related
decision-making.
PMID- 25124944
TI - In vitro and in vivo anti-malarial activity of limonoids isolated from the
residual seed biomass from Carapa guianensis (andiroba) oil production.
AB - BACKGROUND: Carapa guianensis is a cultivable tree used by traditional health
practitioners in the Amazon region to treat several diseases and particularly
symptoms related to malaria. Abundant residual pressed seed material (RPSM)
results as a by-product of carapa or andiroba oil production. The objective of
this study was to evaluate the in vitro and in vivo anti-malarial activity and
cytotoxicity of limonoids isolated from C. guaianensis RPSM. METHODS: 6alpha
acetoxyepoxyazadiradione (1), andirobin (2), 6alpha-acetoxygedunin (3) and 7
deacetoxy-7-oxogedunin (4) (all isolated from RPSM using extraction and
chromatography techniques) and 6alpha-hydroxy-deacetylgedunin (5) (prepared from
3) were evaluated using the micro test on the multi-drug-resistant Plasmodium
falciparum K1 strain. The efficacy of limonoids 3 and 4 was then evaluated orally
and subcutaneously in BALB/c mice infected with chloroquine-sensitive Plasmodium
berghei NK65 strain in the 4-day suppressive test. RESULTS: In vitro, limonoids 1
5 exhibited median inhibition concentrations (IC50) of 20.7-5.0 MUM,
respectively. In general, these limonoids were not toxic to normal cells (MRC-5
human fibroblasts). In vivo, 3 was more active than 4. At oral doses of 50 and
100 mg/kg/day, 3 suppressed parasitaemia versus untreated controls by 40 and 66%,
respectively, evidencing a clear dose-response. CONCLUSION: 6alpha-acetoxygedunin
is an abundant natural product present in C. guianensis residual seed materials
that exhibits significant in vivo anti-malarial properties.
PMID- 25124945
TI - Predictors in adolescence of ESRD in middle-aged men.
AB - BACKGROUND: Identification of predictors of end-stage renal disease (ESRD) in
adolescence could provide intervention targets and improve understanding of the
cause. STUDY DESIGN: Register-based nested case-control study. SETTING &
PARTICIPANTS: A cohort of all Swedish male residents born from 1952 through 1956
who attended mandatory military conscription examinations in late adolescence was
used to identify 534 cases and 5,127 controls matched by birth year, county, and
vital status. PREDICTOR: Erythrocyte sedimentation rate (ESR), proteinuria, blood
pressure, and body mass index (BMI) in late adolescence. OUTCOMES: ESRD (defined
here as dialysis therapy, kidney transplantation, surgical procedures creating
long-term access for dialysis therapy, or chronic kidney disease stage 5) from
1985 through 2009. MEASUREMENTS: Physical working capacity and cognitive function
score in late adolescence. Head of household's occupation and household crowding
measured as person-per-room ratio from the 1960 census when participants were
children. RESULTS: Proteinuria is associated notably with future ESRD, with an
adjusted OR of 7.72 (95% CI, 3.94-15.14; P<0.001) for trace or positive dipstick
findings. ESR has a dose-dependent association with ESRD with an adjusted OR of
2.07 (95%CI, 1.14-3.75; P=0.02) for ESR >15mm/h. Hypertension is associated
strongly with future ESRD with an OR of 3.97 (95%CI, 2.08-7.59; P<0.001) for
grade 2 hypertension and higher. Elevated BMI is associated statistically
significantly with increased ESRD risk with an OR of 3.53 (95%CI, 2.04-6.11;
P<0.001) for BMI >=30 compared with 18.5-<25kg/m(2). LIMITATIONS: The study was
limited to men, with no initial estimation of glomerular filtration rate, and
information on smoking was unavailable. CONCLUSIONS: ESR, proteinuria, BMI, and
blood pressure in late adolescence are independent predictors of ESRD in middle
aged men. This highlights the long natural history and importance of adopting a
life-course approach when considering the cause of chronic kidney disease.
PMID- 25124949
TI - Numbness of the forehead.
PMID- 25124946
TI - Bottom-up impact on the cecidomyiid leaf galler and its parasitism in a tropical
rainforest.
AB - The relative importance of host-plant resources, natural enemies or their
interactions in controlling the population of galling insects and their
parasitism is poorly known for tropical gallers. In this study, we assessed the
impacts of plant quality and density of host trees in regulating the densities of
a galler species, the cecidomyiid leaf galler (Cecidomyiini sp. 1EJV) and its
parasitoids and inquilines on Neoboutonia macrocalyx trees in Uganda. We
manipulated the nutritional quality (or vigour) and the resource concentration
with four levels each of fertilization and the group size of host tree. We then
recorded the effects of these treatments on the growth rate and total leaf area
of host plants, the density of gallers and their mortality by parasitoids and
inquilines. Higher levels of fertilization and host density resulted in
significantly higher total leaf area than did ambient nutrient levels, and lowest
tree densities, respectively. Fertilization also caused significant change in the
growth rate of leaf area. Both higher fertilization and host density caused
higher density of gallers. Total leaf area was positively associated with galler
density, but within galled replicates, the galled leaves were larger than the
ungalled leaves. Although highest levels of fertilization and density of host
trees caused significant change in the densities of parasitoids, the rate of
parasitism did not change. However, tree-density manipulations increased the rate
of inquilinism, but on a very low level. Our results demonstrate a trophic
cascade in the tropical galler and its parasitoids as a response to bottom-up
effects.
PMID- 25124950
TI - Shimmering lights.
PMID- 25124951
TI - Accelerometer-assessed physical activity and diabetic retinopathy in the United
States.
PMID- 25124952
TI - Effect of topical rebamipide on human conjunctival goblet cells.
PMID- 25124953
TI - Tethered vitreous seeds following intravitreal melphalan for retinoblastoma.
PMID- 25124954
TI - Follow-up on anterior chamber angiostrongyliasis.
PMID- 25124955
TI - Vulnerable populations in the underuse of the US Health Care System by persons
with diabetes mellitus and diabetic macular edema.
PMID- 25124956
TI - Vulnerable populations in the underuse of the US Health Care System by persons
with diabetes mellitus and diabetic macular edema-reply.
PMID- 25124957
TI - Making sense of the evidence from the age-related eye disease study 2 randomized
clinical trial.
PMID- 25124958
TI - Making sense of the evidence from the age-related eye disease study 2 randomized
clinical trial-reply.
PMID- 25124960
TI - Melatonin heals the gut.
PMID- 25124959
TI - Uric acid and clinical correlates of endothelial function in kidney transplant
recipients.
AB - Uric acid is associated with increased mortality in kidney transplant recipients
(KTRs), but it is uncertain if this involves endothelial dysfunction. We
hypothesized, first, that there was an association between uric acid and
endothelial function, and second, that there were associations between
endothelial function and cardiac and mortality risk scores. METHODS: One hundred
and fifty-two patients were examined 10 wk after kidney transplantation by two
measures of endothelial function, the brachial artery flow-mediated dilatation
(FMD) expressed as percent dilatation (FMD%), and fingertip peripheral arterial
tone (PAT) expressed as log-reactive hyperemia index (LnRHI). Risk scores were
calculated from a recently validated formula. Other clinical correlates of
endothelial function were described in stepwise linear regression models.
RESULTS: Uric acid was associated negatively with FMD% in an age- and gender
adjusted model, while not in the multivariable model. No association was shown
between uric acid and LnRHI. FMD% was associated negatively with risk scores in
both crude and age- and gender-adjusted models (p < 0.01). LnRHI was associated
negatively with risk scores in the latter model only (p < 0.05). CONCLUSIONS:
Uric acid was neither associated with FMD% nor LnRHI in KTRs. There were
significant associations between endothelial function indices and cardiac and
mortality risk scores.
PMID- 25124961
TI - Introduction to special issue on microbiome influences on host immunity.
PMID- 25124962
TI - MyD88 acts as an adaptor protein for inflammatory signalling induced by amyloid
beta in macrophages.
AB - Neuroinflammation is the complex innate immune response of neural tissue to
control infection, and Toll-like receptors (TLRs), a major family of pattern
recognition receptors (PRRs), have a key role in Alzheimer's disease (AD)
progression. Innate immune cells, including macrophages, govern tailored
inflammatory gene expression to regulate inflammatory responses, however the role
of macrophages in AD pathogenesis is not clear. All TLRs, with the exception of
TLR3, recruit the MyD88 adaptor, and evidence indicates a role for this adaptor
in inflammatory and cognitive changes in mouse AD models, in addition to amyloid
beta (Abeta)-induced inflammatory signalling at a cellular level. In the present
study, we employed the use of Abeta to induce inflammatory signalling in
immortalized macrophages. Data presented herein demonstrate that Abeta promoted
the nuclear sequestration of NF-kappaB, and polarized macrophages to an M1
phenotype with downstream consequences on pro-inflammatory cytokine expression.
Importantly, Abeta-induced TNF-alpha production was exacerbated in macrophages
lacking MyD88, while MyD88 deficiency promoted NF-kappaB activation, enhanced M1
and M2 polarization, and compromised macrophage viability. We demonstrate that in
the absence of MyD88, mitogen-activated protein kinase (MAPKs) act as upstream
signalling intermediates targeted by Abeta in the cascade leading to TNF-alpha
expression. Our findings offer a new role for MyD88 in cellular mechanisms
underlying AD pathogenesis, indicating that MyD88 adaptors are key in regulating
Abeta-induced inflammatory signalling in macrophages.
PMID- 25124963
TI - Involvement of IL-6 and IL-1 receptor antagonist on intellectual disability.
AB - Imbalances in the regulation of pro-inflammatory cytokines have been increasingly
correlated with several neurodevelopmental disorders and their role in neuronal
development is being investigated. To assess the possible influence of cytokines
on the onset of intellectual disability (ID), we studied the polymorphisms of
thirteen proinflammatory cytokine genes in 81 patients and 61 healthy controls.
We demonstrated a significant association of interleukin-6 (IL-6) single
nucleotide polymorphism (SNP) (-174 G/C and nt565 G/A), and interleukin-1
receptor antagonist (IL-1RA) (Mspa-I 11100) SNP with ID. Moreover, the IL-6 SNPs
is an unfavorable genetic predisposition for females. The evaluation of
circulating levels of IL-6 and IL-1RA showed that the serum concentrations of IL
6 were significantly higher in ID patients than in controls. These data suggest
that functional cytokine gene polymorphisms may influence the development of ID.
PMID- 25124964
TI - The growth of human scalp hair in females using visible red light laser and LED
sources.
AB - BACKGROUND AND OBJECTIVES: Low level laser (light) therapy (LLLT) has been
demonstrated to promote hair growth in males. A double-blind randomized
controlled trial was undertaken to define the safety and physiologic effects of
LLLT on females with androgenic alopecia. METHODS: Forty-seven females (18-60
years old, Fitzpatrick I-IV, and Ludwig-Savin Baldness Scale I-2, I-3, I-4, II-1,
II-2 baldness patterns) were recruited. A transition zone scalp site was
selected; hairs were trimmed to 3 mm height; the area was tattooed and
photographed. The active group received a "TOPHAT655" unit containing 21, 5 mW
diode lasers (655 +/- 5 nm) and 30 LEDS (655 +/- 20 nm), in a bicycle-helmet like
apparatus. The placebo group unit appeared identical, containing incandescent red
lights. Patients treated at home every other day * 16 weeks (60 treatments, 67
J/cm(2) irradiance/25 minute treatment, 2.9 J dose), with follow up and
photography at 16 weeks. A masked 2.85 cm(2) photographic area was evaluated by
another blinded investigator. The primary endpoint was the percent increase in
hair counts from baseline. RESULTS: Forty-two patients completed the study (24
active, 18 sham). No adverse events or side effects were reported. Baseline hair
counts were 228.2 +/- 133.4 (N = 18) in the sham and 209.6 +/- 118.5 (N = 24) in
the active group (P = 0.642). Post Treatment hair counts were 252.1 +/- 143.3 (N
= 18) in the sham group and 309.9 +/- 166.6 (N = 24) in the active group (P =
0.235). The change in hair counts over baseline was 23.9 +/- 30.1 (N = 18) in the
sham group and 100.3 +/- 53.4 (N = 24) in the active group (P < 0.0001). The
percent hair increase over the duration of the study was 11.05 +/- 48.30 (N = 18)
for the sham group and 48.07 +/- 17.61 (N = 24) for the active group (P < 0.001).
This demonstrates a 37% increase in hair growth in the active treatment group as
compared to the placebo group. CONCLUSIONS: LLLT of the scalp at 655 nm
significantly improved hair counts in women with androgenetic alopecia at a rate
similar to that observed in males using the same parameters.
PMID- 25124965
TI - Using virtual human technology to provide immediate feedback about participants'
use of demographic cues and knowledge of their cue use.
AB - Demographic characteristics have been found to influence pain management
decisions, but limited focus has been placed on participants' reactions to
feedback about their use of sex, race, or age to make these decisions. The
present study aimed to examine the effects of providing feedback about the use of
demographic cues to participants making pain management decisions. Participants
(N = 107) viewed 32 virtual human patients with standardized levels of pain and
provided ratings for virtual humans' pain intensity and their treatment
decisions. Real-time lens model idiographic analyses determined participants'
decision policies based on cues used. Participants were subsequently informed
about cue use and completed feedback questions. Frequency analyses were conducted
on responses to these questions. Between 7.4 and 89.4% of participants indicated
awareness of their use of demographic or pain expression cues. Of those
individuals, 26.9 to 55.5% believed this awareness would change their future
clinical decisions, and 66.6 to 75.9% endorsed that their attitudes affect their
imagined clinical practice. Between 66.6 and 79.1% of participants who used cues
reported willingness to complete an online tutorial about pain across demographic
groups. This study was novel because it provided participants feedback about
their cue use. Most participants who used cues indicated willingness to
participate in an online intervention, suggesting this technology's utility for
modifying biases. PERSPECTIVE: This is the first study to make individuals aware
of whether a virtual human's sex, race, or age influences their decision making.
Findings suggest that a majority of the individuals who were made aware of their
use of demographic cues would be willing to participate in an online
intervention.
PMID- 25124966
TI - Suture granuloma mimicking a recurrent sacro-coccygeal pilonidal sinus after
Limberg flap.
AB - Sacro-coccygeal pilonidal sinus disease is classified as an asymptomatic, acutely
abscess-forming or chronic subcutaneous inflammation in the sacro-coccygeal
region featuring characteristic pits in the bottom cleft. Due to high rates of
recurrence, two flap techniques have been established in the course of the past
three decades. One of them is the Karydakis operation, the other option is a
rotation flap named Limberg procedure. We report about a case of suture granuloma
in the area of a Limberg flap after recurrent pilonidal sinus with extrusion of
the suture material, thus mimicking recurrence. In case of recurrent pilonidal
sinus following plastic coverage or primary closure, respectively, the
differential diagnosis of suture granuloma should be considered.
PMID- 25124968
TI - Predictive findings of allergic disease in fiberoptic nasolaryngoscopy.
AB - OBJECTIVES/HYPOTHESIS: To determine whether findings on fiberoptic
nasolaryngoscopy beyond the nasal cavity can aid in diagnosis of atopy. STUDY
DESIGN: Case control analysis of patients undergoing fiberoptic nasolaryngoscopy
and allergy testing at a single academic institution. METHODS: Patients who
underwent flexible nasolaryngoscopy for either laryngeal or nasal symptoms and
allergy testing by in vitro methods were divided into an atopic group and a
nonatopic control group based on results of allergy testing. Three board
certified otolaryngologists who were blinded to the atopic status and symptoms
viewed 88 patient videos and filled out an 8-item endoscopic rating questionnaire
for each. Correlation between rater scores, endoscopic findings, and atopic
status was calculated using Randolph's multirater kappa values and Mann-Whitney
test. RESULTS: Intrarater reliability was moderate to perfect for all physicians
on all questions (kappa 0.545-1.0). Inter-rater reliability was slight to fair
(kappa 0.143-0.399) for all questions and the overall impression of atopic
disease. Abnormalities of the torus tubarius (P = .007) and increased
nasopharyngeal secretions (P = .038) were predictive of atopic disease, whereas
the presence of an adenoid (P = .08) and impression of atopic disease (P = .15)
approached significance. All other endoscopic measures were not predictive of
atopic status. CONCLUSIONS: Fiberoptic nasolaryngeal findings within the
nasopharynx rather than the larynx are predictive of a positive atopic status.
LEVEL OF EVIDENCE: 3b.
PMID- 25124967
TI - The FGF-1-specific single-chain antibody scFv1C9 effectively inhibits breast
cancer tumour growth and metastasis.
AB - Immunotherapy mediated by recombinant antibodies is an effective therapeutic
strategy for a variety of cancers. In a previous study, we demonstrated that the
fibroblast growth factor 1 (FGF-1)-specific recombinant antibody scFv1C9 arrests
the cell cycle at the G0/G1 transition by blocking the intracrine FGF-1 pathway
in breast cancer cells. Here, we further show that the overexpression of scFv1C9
in MCF-7 and MDA-MB-231 breast cancer cells by lentiviral infection resulted in
decreased tumourigenicity, tumour growth and lung metastasis through FGF-1
neutralization. We found that scFv1C9 resulted in the up-regulation of p21, which
in turn inhibited the expression of CDK2 and blocked cell cycle progression. To
explore the potential role of scFv1C9 in vivo, we delivered the gene into solid
tumours by electroporation, which resulted in significant inhibition of tumour
growth. In tumour tissue sections, immunohistochemical staining of the cellular
proliferation marker Ki-67 and the microvessel marker CD31 showed a reduction in
the proliferative index and microvessel density, respectively, upon expression of
scFv1C9 compared with the appropriate controls. Thus, our data indicate a central
role for scFv1C9 in blocking the intracrine pathway of FGF-1, therefore, scFv1C9
could be developed in an effective therapeutic for breast cancer.
PMID- 25124969
TI - Dosage individualization in children: integration of pharmacometrics in clinical
practice.
AB - BACKGROUND: Children are in a continuous and dynamically changing state of growth
and development. A thorough understanding of developmental pharmacokinetics (PK)
and pharmacodynamics (PD) is required to optimize drug therapy in children. DATA
SOURCES: Based on recent publications and the experience of our group, we present
an outline on integrating pharmacometrics in pediatric clinical practice to
develop evidence-based personalized pharmacotherapy. RESULTS: Antibiotics in
septic neonates and immunosuppressants in pediatric transplant recipients are
provided as proof-of-concept to demonstrate the utility of pharmacometrics in
clinical practice. Dosage individualization based on developmental PK-PD model
has potential benefits of improving the efficacy and safety of drug therapy in
children. CONCLUSION: The pharmacometric technique should be better developed and
used in clinical practice to personalize drug therapy in children in order to
decrease variability of drug exposure and associated risks of overdose or
underdose.
PMID- 25124970
TI - The role of surfactant and non-invasive mechanical ventilation in early
management of respiratory distress syndrome in premature infants.
AB - BACKGROUND: Surfactant replacement therapy has been used for few decades for the
treatment of respiratory distress syndrome (RDS) and has significantly improved
morbidity and mortality in premature infants. Non-invasive respiratory support
has recently emerged as a strategy in the early management of RDS. In this
review, we discuss the different strategies of early management of RDS. DATA
SOURCES: A literature search of PubMed database was conducted to review the
subject. The quality of evidence of key clinical studies was graded according to
a modified grading system of the international GRADE group. RESULTS: Continuous
positive airway pressure (CPAP) with selective surfactant is a safe alternative
to routine intubation, surfactant and mechanical ventilation in preterm infants
with spontaneous breathing, and such an approach has been associated with
decreased risk of death and bronchopulmonary dysplasia. There is a risk of
pneumothorax when using a high pressure of CPAP (>=8 cm of H2O), a high partial
pressure of carbon dioxide (PCO2 >75 mm of Hg), and a high fraction of inspired
oxygen (FiO2 >0.6) as a threshold for intubation while on CPAP. CONCLUSION: Not
all preterm infants need surfactant treatment, and non-invasive respiratory
support is a safe and effective approach.
PMID- 25124971
TI - Bilirubin nomograms for identification of neonatal hyperbilirubinemia in healthy
term and late-preterm infants: a systematic review and meta-analysis.
AB - BACKGROUND: Hyperbilirubinemia occurs in most healthy term and late-preterm
infants, and must be monitored to identify those who might develop severe
hyperbilirubinemia. Total serum bilirubin (TSB) or transcutaneous bilirubin (TcB)
nomograms have been developed and validated to identify neonatal
hyperbilirubinemia. This study aimed to review previously published studies and
compare the TcB nomograms with the TSB nomogram, and to determine if the former
has the same predictive value for significant hyperbilirubinemia as TSB nomogram
does. METHODS: A predefined search strategy and inclusion criteria were set up.
We selected studies assessing the predictive ability of TSB/TcB nomograms to
identify significant hyperbilirubinemia in healthy term and late-preterm infants.
Two independent reviewers assessed the quality and extracted the data from the
included studies. Meta-Disc 1.4 analysis software was used to calculate the
pooled sensitivity, specificity, and positive likelihood ratio of TcB/TSB
nomograms. A pooled summary of the receiver operating characteristic of the
TcB/TSB nomograms was created. RESULTS: After screening 187 publications from
electronic database searches and reference lists of eligible articles, we
included 14 studies in the systematic review and meta-analysis. Eleven studies
were of medium methodological quality. The remaining three studies were of low
methodological quality. Seven studies evaluated the TcB nomograms, and seven
studies assessed TSB nomograms. There were no differences between the predictive
abilities of the TSB and TcB nomograms (the pooled area under curve was 0.819 vs.
0.817). CONCLUSIONS: This study showed that TcB nomograms had the same predictive
value as TSB nomograms, both of which could be used to identify subsequent
significant hyperbilirubinemia. But this result should be interpreted cautiously
because some methodological limitations of these included studies were identified
in this review.
PMID- 25124973
TI - No relationship between mode of delivery and neonatal mortality and
neurodevelopment in very low birth weight infants aged two years.
AB - BACKGROUND: To compare neonatal mortality and neurodevelopmental outcomes at two
years of age in very low birth weight infants (<=1500 g) born by cesarean with
those by vaginal delivery. METHODS: In this retrospective, case-control study, we
evaluated neonatal mortality, medical conditions and neurodevelopmental outcomes
at two years of corrected age in 710 very low birth weight (VLBW) infants born
between January 2005 and December 2010. Of the 710 infants, 351 were born by the
cesarean and 359/710 by vaginal route. RESULTS: There were no significant
differences in neonatal mortality between the cesarean delivery group and vaginal
delivery group [56/351 (15.9%) vs. 71/359 (19.8%), P=0.20]. VLBW infants
delivered by the cesarean procedure had a higher incidence of respiratory
distress syndrome than those born by the vaginal route [221/351 (63.0%) vs.
178/359 (49.6%), P<0.001]. There were no differences in other neonatal
morbidities, including intraventricular hemorrhage [126/351 (35.9%) vs. 134/359
(37.3%), P=0.69], bronchopulmonary dysplasia [39/351 (11%) vs. 31/359 (8.6%),
P=0.38] and necrotising enterocolitis [40/351 (11.4%) vs. 32/359 (8.9%), P=0.32]
between the two groups. The incidence of poor neurodevelopment after cesarean
delivery was similar to that after vaginal delivery [105/351 (29.9) vs. 104/359
(29.0%), P=0.78]. CONCLUSIONS: In neither neurodevelopment nor neonatal mortality
did cesarean birth offered significant advantages to VLBW infants. Moreover, the
operation might be associated with an increased risk of respiratory distress
syndrome for VLBW infants. The mode of delivery of VLBW infants should be largely
based on obstetric indications and maternal considerations rather than perceived
better outcomes for the neonate.
PMID- 25124972
TI - QDPR gene mutation and clinical follow-up in Chinese patients with
dihydropteridine reductase deficiency.
AB - BACKGROUND: This study aimed to investigate the mutation spectrum of the QDPR
gene, to determine the effect of mutations on dihydropteridine reductase (DHPR)
structure/function, to discuss the potential genotypephenotype correlation, and
to evaluate the clinical outcome of Chinese patients after treatment. METHODS:
Nine DHPR-deficient patients were enrolled in this study and seven of them
underwent neonatal screening. QDPR gene mutations were analyzed and confirmed by
routine methods. The potential pathogenicity of missense variants was analyzed
using Clustal X, PolyPhen program and Swiss-PDB Viewer 4.04_OSX software,
respectively. The clinical outcomes of the patients were evaluated after long
term treatment. RESULTS: In 10 mutations of the 9 patients, 4 were novel
mutations (G20V, V86D, G130S and A175R), 4 were reported by us previously, and 2
known mutations were identified. R221X was a hotspot mutation (27.7%) in our
patients. Eight missense mutations probably had damage to protein. Six patients
in this series were treated with a good control of phenylalanine level. The
height and weight of the patients were normal at the age of 4 months to 7.5
years. Four patients, who underwent a neonatal screening and were treated early,
showed a normal mental development. In 2 patients diagnosed late, neurological
symptoms were significantly improved. CONCLUSIONS: The mutation spectrum of the
QDPR gene is different in the Chinese population. Most mutations are related to
severe phenotype. The determination of DHPR activity should be performed in
patients with hyperphenylalaninemia. DHPR-deficient patients who were treated
below the age of 2 months may have a near normal mental development.
PMID- 25124974
TI - Effect of pravastatin on endothelial dysfunction in children with medium to giant
coronary aneurysms due to Kawasaki disease.
AB - BACKGROUND: Ongoing low-grade inflammation and endothelial dysfunction persist in
children with coronary lesions diagnosed with Kawasaki disease (KD). Statins,
frequently used in the management of high cholesterol, have also shown to improve
surrogate markers of inflammation and endothelial dysfunction. This study was
undertaken to investigate the efficacy and safety of pravastatin in children with
coronary artery aneurysms due to KD. METHODS: The study enrolled 14 healthy
children and 13 male children, aged 2-10 years, with medium-to-giant coronary
aneurysms for at least 12 months after the onset of KD. Pravastatin was given
orally to the KD group at a dose of 5 mg/day for children under 5 and 10 mg/day
for children older than 5 years. To determine the effects of pravastatin on
endothelial function, high-frequency ultrasound was performed before the start of
the study and 6 months after pravastatin therapy. The parameters measured were
brachial artery flow-mediated dilation (FMD), non-flow mediated dilation (NMD),
and carotid artery stiffness index (SI). High sensitive C-reactive protein (hs
CRP) levels, the circulating endothelial progenitor cells (EPCs) number, and
serum lipid profiles were also determined at baseline and after 6 months of
pravastatin treatment. RESULTS: Before treatment, the KD group had significantly
decreased FMD (P<0.05) and increased SI and hs-CRP levels (P<0.05) compared with
controls. After 6 months of pravastatin therapy, FMD improved significantly
compared to the baseline KD group (3.16+/-6.49 to 10.05+/-7.74, P<0.05), but
remained significantly less than that in the control group with no significant
changes in NMD and SI. There were significant decreases in markers of
inflammation after treatment. The hs-CRP levels decreased significantly from
2.93+/-0.81 mmol/L to 2.14+/-0.82 mmol/L (P<0.05) and the serum apo-B and apo
B/apo-A1 ratio were also reduced (P<0.05) in the KD group. However, the
circulating EPC number was not significantly different between baseline and that
following pravastatin treatment in the KD group and the control group (P>0.05).
No significant complications were noted with paravastatin therapy. CONCLUSIONS:
Pravastatin improves endothelial function and reduces low-grade chronic
inflammation in patients with coronary aneurysms due to KD. Children with
coronary aneurysms due to KD may benefit from statin therapy.
PMID- 25124975
TI - Congenital duodenal obstruction in neonates: a decade's experience from one
center.
AB - BACKGROUND: Congenital duodenal obstruction (CDO) is one of the most common
anomalies in newborns, and accounting for nearly half of all cases of neonatal
intestinal obstruction. This study aimed to review our single-center experience
in managing congenital duodenal obstruction while evaluate the outcomes. METHODS:
We conducted a retrospective analysis of the records of all neonates dianogsed
with congenital duodenal obstruction admitted to our center between January 2003
and December 2012. We analyzed demographic criteria, clinical manifestations,
associated anomalies, radiologic findings, surgical methods, postoperative
complications, and final outcomes. RESULTS: The study comprised 287 newborns (193
boys and 94 girls). Birth weight ranged from 950 g to 4850 g. Fifty-three
patients were born prematurely between 28 and 36 weeks' gestation. Malrotation
was diagnosed in 174 patients, annular pancreas in 66, duodenal web in 55,
duodenal atresia or stenosis in 9, preduodenal portal vein in 2, and congenital
band compression in 1. Twenty patients had various combinations of these
conditions. Presenting symptoms included bilious vomiting, dehydration, and
weight loss. X-rays of the upper abdomen demonstrated the presence of a typical
double-bubble sign or air-fluid levels in 68.64% of patients, and confirmatory
upper and/or lower gastrointestinal contrast studies were obtained in 64.11%.
Multiple associated abnormalities were observed in 50.52% of the patients.
Various surgical approaches were used, including Ladd's procedure, duodenoplasty,
duodenoduodenostomy, duodenojejunostomy, or a combination of these. Seventeen
patients died postoperatively and 14 required re-operation. CONCLUSIONS:
Congenital duodenal obstruction is a complex entity with various etiologies and
often includes multiple concomitant disorders. Timely diagnosis and aggressive
surgery are key to improving prognosis. Care should be taken to address all of
the causes of duodenal obstruction and/or associated alimentary tract anomalies
during surgery.
PMID- 25124976
TI - Somatic growth of lean children: the potential role of sleep.
AB - BACKGROUND: Despite the current obesity pandemic, childhood malnutrition remains
an urgent, public health concern. Similar to the obesity pandemic, childhood
malnutrition is influenced by genetic and a number of social, environmental and
biological factors. In this study, we investigated the association between sleep
duration and somatic growth in lean children. METHODS: A stratified, randomly
clustered sampling design was used to select fifth grade students from 10 primary
schools in Shanghai. Based on a body mass index below the 15th percentile a
subsample of 143 lean children aged 10-11 years old was defined. Sleep duration
and other potential confounders were surveyed through parental or self-report
questionnaires. Body measurements were collected and used to calculate the Z
score of weight, height, body mass index as well as body fat percentage. RESULTS:
Compared with children who slept <9 hours, those who slept for >=10 hours grew
taller and gained more weight after adjusting for confounding factors. When
children slept 9-10 hours, they had significantly higher Z score of weight and
body mass index. CONCLUSIONS: Prolonged sleep not only benefits weight gain but
also improves height in lean children. Our findings might provide important
public health advice such that prolonged sleep may be an effective modifier of
nutritional problems in childhood.
PMID- 25124977
TI - Improved outcomes of transported neonates in Beijing: the impact of strategic
changes in perinatal and regional neonatal transport network services.
AB - BACKGROUND: Infants born outside perinatal centers may have compromised outcomes
due to the transfer speed and efficiency to an appropriate tertiary center. This
study aimed to evaluate the impact of regional coordinated changes in perinatal
supports and retrieval services on the outcome of transported neonates in
Beijing, China. METHODS: Information about transported newborns between phase 1
(July 1, 2004 to June 30, 2006) and phase 2 (July 1, 2007 to June 30, 2009) was
collected. The strategic changes during phase 2 included standardized neonatal
transport procedures, skilled attendants, a perinatal consulting service, and
preferential admission of transported neonates to the intensive care unit of the
tertiary care center. Data from phase 2 (after-strategic changes) were compared
with those of phase 1 (the period of pre-strategic changes) after a 12-month
washout period, especially regarding the reduction in mortality and selected
morbidity. RESULTS: There was a large increase in the number of transported
infants in phase 2 compared with phase 1 (2797 vs. 567 patients). The average
monthly rate of increase of transported infants was 383.3% (from 24 infants per
month to 116 infants per month). The mortality rate of transported neonates
reduced significantly from phase 1 to phase 2 (5.11% vs. 2.82%; P=0.005),
particularly for preterm infants (8.47% vs. 4.34%; P=0.006). In addition,
transported neonates during phase 2 had significantly decreased morbidities.
CONCLUSIONS: Regional coordinated strategies optimizing the perinatal services
and transport of outborn sick and preterm infants to tertiary care centers
improved survival outcomes considerably. These findings have vital implications
for health outcomes and resource planning.
PMID- 25124978
TI - Placental growth factor expression is reversed by antivascular endothelial growth
factor therapy under hypoxic conditions.
AB - BACKGROUND: Clinical trials have revealed that the antivascular endothelial
growth factor (VEGF) therapies are effective in retinopathy of prematurity (ROP).
But the low level of VEGF was necessary as a survival signal in healthy
conditions, and endogenous placental growth factor (PIGF) is redundant for
development. The purpose of this study was to elucidate the PIGF expression under
hypoxia as well as the influence of anti-VEGF therapy on PIGF. METHODS: CoCl2
induced hypoxic human umbilical vein endothelial cells (HUVECs) were used for an
in vitro study, and oxygen-induced retinopathy (OIR) mice models were used for an
in vivo study. The expression patterns of PIGF under hypoxic conditions and the
influence of anti-VEGF therapy on PIGF were evaluated by quantitative reverse
transcription-polymerase chain reaction (RTPCR). The retinal avascular areas and
neovascularization (NV) areas of anti-VEGF, anti-PIGF and combination treatments
were calculated. Retina PIGF concentration was evaluated by ELISA after
treatment. The vasoactive effects of exogenous PIGF on HUVECs were investigated
by proliferation and migration studies. RESULTS: PIGF mRNA expression was reduced
by hypoxia in OIR mice, in HUVECs under hypoxia and anti-VEGF treatment. However,
PIGF expression was reversed by anti-VEGF therapy in the OIR model and in HUVECs
under hypoxia. Exogenous PIGF significantly inhibited HUVECs proliferation and
migration under normal conditions, but it stimulated cell proliferation and
migration under hypoxia. Anti-PIGF treatment was effective for neovascular tufts
in OIR mice (P<0.05). CONCLUSION: The finding that PIGF expression is
iatrogenically up-regulated by anti-VEGF therapy provides a consideration to
combine it with anti-PIGF therapy.
PMID- 25124979
TI - Clinical characteristics and mutation analysis of three Chinese children with
autosomal recessive polycystic kidney disease.
AB - BACKGROUND: There are few studies on the genotypes and phenotypes of autosomal
recessive polycystic kidney disease in Chinese patients. METHODS: PKHD1 mutations
in three children were detected with PCR and direct sequencing, and their
clinical data were retrospectively reviewed. RESULTS: All of the children had
bilateral enlarged polycystic kidneys, congenital hepatic fibrosis and
intrahepatic bile duct dilatation. One of three children had classical multiple
small cysts throughout the kidneys, and the other two children had bilateral
multiple renal cysts of various sizes. Two children had abnormally shaped livers,
portal hypertension and splenomegaly. Two heterozygous mutations (p.T36M, and
p.P137S) were detected in Patient 1 and two were detected in Patient 2 (p.L2658X
and p.V836A). One heterozygous mutation (p.L1425R) was detected in Patient 3.
CONCLUSIONS: The study shows that renal and liver phenotypes of the Chinese
children varied. Five mutations were identified in the three children, three of
which were novel mutations.
PMID- 25124980
TI - A novel CLCN5 mutation in a Chinese boy with Dent's disease.
AB - BACKGROUND: Dent's disease is a rare X-linked recessive hereditary disease caused
by mutations in either the CLCN5 or OCRL1 genes. This disease is characterized by
manifestations of proximal renal tubule dysfunction associated with low molecular
weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, nephrolithiasis, and
progressive renal failure. METHODS: We report a Chinese boy with Dent's disease,
clinically diagnosed by LMWP and hypercalciuria. Genetic analysis was made of the
CLCN5 and OCRL1 genes. Related studies were also reviewed. RESULTS: A splice site
mutation IVS6, +2T>C of the CLCN5 gene was revealed in this case, and it was not
reported previously. CONCLUSIONS: Clinical and genetic analysis is valuable for
the diagnosis of Dent's disease. A novel mutation in the CLCN5 gene was
identified in our patient.
PMID- 25124981
TI - GATA3 mutation in a family with hypoparathyroidism, deafness and renal dysplasia
syndrome.
AB - BACKGROUND: The hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome
is an autosomal dominant disorder primarily caused by GATA3 gene mutation. We
report here a case that both of a Chinese boy and his father had HDR syndrome
which caused by a novel mutation of GATA3. METHODS: Polymerase chain reaction and
DNA sequencing was performed to detect the exons of the GATA3 gene for mutation
analysis. RESULTS: Sequence analysis of GATA3 revealed a heterozygous nonsense
mutation in this family: a mutation of GATA3 at exon 2 (c.515C >A) that resulted
in a premature stop at codon 172 (p.S172X) with a loss of two zinc finger
domains. CONCLUSION: We identified a novel nonsense mutation which will expand
the spectrum of HDR-associated GATA3 mutations.
PMID- 25124982
TI - Impact of caffeine and coffee on our health.
AB - Coffee is the most frequently consumed caffeine-containing beverage. The caffeine
in coffee is a bioactive compound with stimulatory effects on the central nervous
system and a positive effect on long-term memory. Although coffee consumption has
been historically linked to adverse health effects, new research indicates that
coffee consumption may be beneficial. Here we discuss the impact of coffee and
caffeine on health and bring attention to the changing caffeine landscape that
includes new caffeine-containing energy drinks and supplements, often targeting
children and adolescents.
PMID- 25124984
TI - Reconceptualising the doctor-patient relationship: recognising the role of trust
in contemporary health care.
AB - The conception of the doctor-patient relationship under Australian law has
followed British common law tradition whereby the relationship is founded in a
contractual exchange. By contrast, this article presents a rationale and
framework for an alternative model-a "Trust Model"-for implementation into law to
more accurately reflect the contemporary therapeutic dynamic. The framework has
four elements: (i) an assumption that professional conflicts (actual or
perceived) with patient safety, motivated by financial or personal interests,
should be avoided; (ii) an onus on doctors to disclose these conflicts; (iii) a
proposed mechanism to contend with instances where doctors choose not to
disclose; and (iv) sanctions for non-compliance with the regime.
PMID- 25124985
TI - Cytometric analysis of surface molecules of leucocytes and phagocytic activity of
granulocytes and monocytes/macrophages in cows with pyometra.
AB - Pyometra is a serious problem in dairy cow herds, causing large economic losses
due to infertility. The development of pyometra depends mainly on the
immunological status of the cow. The aim of the study was a comparative
evaluation of selected indicators involving non-specific and specific immunity in
cows with pyometra and in cows without inflammation of the uterus. The study was
performed in 20 cows, which were divided into two groups: pyometra group and
healthy group, each comprising 10 cows, based on the results of cytological and
ultrasonographic tests. A flow cytometric analysis was performed for the surface
molecules CD4, CD8, CD14, CD21, CD25 and CD4(+) CD25(+) on leucocytes, and the
phagocytic activity was determined from granulocytes and monocytes/macrophages in
the peripheral blood and uterine washings, respectively. It was demonstrated that
the percentage of phagocytic granulocytes and monocytes/macrophages in both the
peripheral blood and uterine washings was significantly lower in cows with
pyometra compared with the healthy group (p < 0.001). Significantly (p <= 0.001)
lower percentage of CD4(+) , CD14(+) , CD25(+) and CD4(+) CD25(+) phenotype
leucocytes was also observed in the peripheral blood of cows from the pyometra
group, along with a significantly higher (p < 0.001) percentage of CD8(+) and
CD21(+) lymphocytes as compared to the healthy group. The results of work
indicate that disfunction of cell immunity coexisting with pyometra may be caused
by a bacterial infection and the presence of blocking agents (IL-10), released by
the increasing number of CD8(+) lymphocytes what leads to the advanced
inflammation of uterus.
PMID- 25124986
TI - Oxygen reduction reaction in a droplet on graphite: direct evidence that the edge
is more active than the basal plane.
AB - Carbon-based metal-free electrocatalysts for the oxygen reduction reaction (ORR)
in alkaline medium have been extensively investigated with the aim of replacing
the commercially available, but precious platinum-based catalysts. For the proper
design of carbon-based metal-free electrocatalysts for the ORR, it would be
interesting to identify the active sites of the electrocatalyst. The ORR was now
studied with an air-saturated electrolyte solution droplet (diameter ca. 15 MUm),
which was deposited at a specified position either on the edge or on the basal
plane of highly oriented pyrolytic graphite. Electrochemical measurements suggest
that the edge carbon atoms are more active than the basal-plane ones for the ORR.
This provides a direct way to identify the active sites of carbon materials for
the ORR. Ball-milled graphite and carbon nanotubes with more exposed edges were
also prepared and showed significantly enhanced ORR activity. DFT calculations
elucidated the mechanism by which the charged edge carbon atoms result in the
higher ORR activity.
PMID- 25124983
TI - Questions and answers on the Belgian model of integral end-of-life care:
experiment? Prototype? : "Eu-euthanasia": the close historical, and evidently
synergistic, relationship between palliative care and euthanasia in Belgium: an
interview with a doctor involved in the early development of both and two of his
successors.
AB - This article analyses domestic and foreign reactions to a 2008 report in the
British Medical Journal on the complementary and, as argued, synergistic
relationship between palliative care and euthanasia in Belgium. The earliest
initiators of palliative care in Belgium in the late 1970s held the view that
access to proper palliative care was a precondition for euthanasia to be
acceptable and that euthanasia and palliative care could, and should, develop
together. Advocates of euthanasia including author Jan Bernheim, independent from
but together with British expatriates, were among the founders of what was
probably the first palliative care service in Europe outside of the United
Kingdom. In what has become known as the Belgian model of integral end-of-life
care, euthanasia is an available option, also at the end of a palliative care
pathway. This approach became the majority view among the wider Belgian public,
palliative care workers, other health professionals, and legislators. The legal
regulation of euthanasia in 2002 was preceded and followed by a considerable
expansion of palliative care services. It is argued that this synergistic
development was made possible by public confidence in the health care system and
widespread progressive social attitudes that gave rise to a high level of
community support for both palliative care and euthanasia. The Belgian model of
so-called integral end-of-life care is continuing to evolve, with constant
scrutiny of practice and improvements to procedures. It still exhibits several
imperfections, for which some solutions are being developed. This article
analyses this model by way of answers to a series of questions posed by Journal
of Bioethical Inquiry consulting editor Michael Ashby to the Belgian authors.
PMID- 25124987
TI - Smoking ban is upheld at Scotland's State Hospital despite patient's earlier
victory.
PMID- 25124988
TI - Identification of promoter polymorphisms in the cytochrome P450 CYP6AY1 linked
with insecticide resistance in the brown planthopper, Nilaparvata lugens.
AB - Imidacloprid resistance in the brown planthopper, Nilaparvata lugens, is
primarily the result of the over-expression of cytochrome P450 monooxygenases.
Here, a field-collected strain of N. lugens was shown to be highly resistant to
both imidacloprid and buprofezin. Insecticide exposure and quantitative real-time
PCR revealed that its resistance was mainly associated with a cytochrome P450
gene, CYP6AY1. CYP6AY1 is known to metabolize imidacloprid but its effect on
buprofezin is unclear. In the 5'-untranslated region of CYP6AY1, a novel
alternative splicing was detected. After a 1990-bp promoter region was cloned,
its basal luciferase activity was assessed. Furthermore, genotyping studies
identified 12 variations in the promoter region that discriminated between the
field-collected and control strain. Finally, survival bioassays revealed a single
nucleotide polymorphism and an insertion-deletion polymorphism linked to
buprofezin and imidacloprid resistance. Mutagenesis of these sites enhanced the
promoter activity of CYP6AY1. These results suggest that promoter polymorphisms
may affect P450-mediated multiple insecticide resistance of pests.
PMID- 25124989
TI - Breaking the trade-off between thermal and electrical conductivities in the
thermoelectric material of an artificially tilted multilayer.
AB - Breaking the trade-off between thermoelectric (TE) parameters has long been
demanded in order to highly enhance its performance. Here, we report the 'trade
off-free' interdependence between thermal conductivity (kappa) and resistivity
(rho) in a TE/metal tilted multilayer and significant enhancement of TE power
generation based on the off-diagonal thermoelectric (ODTE) effect, which
generates transverse electrical current in response to vertical thermal current.
rho and kappa can be simultaneously decreased by setting charge flow along more
electrically conductive layer and thermal flow across less-thermally conductive
perpendicular direction by decreasing the tilting angle. Moreover, introducing
porosity in the metal layer enables to decrease in kappa without changing rho,
because the macroscopic rho and kappa of the tilted multilayer is respectively
governed by the properties of the TE material and the metal with large
dissimilarity. The obtained results reveal new strategies for developing trade
off-free TE materials, which will stimulate practical use of TE conversion for
waste-heat recovery.
PMID- 25124990
TI - Spatial and temporal analysis of land cover changes and water quality in the Lake
Issaqueena watershed, South Carolina.
AB - Monitoring changes in land cover and the subsequent environmental responses are
essential for water quality assessment, natural resource planning, management,
and policies. Over the last 75 years, the Lake Issaqueena watershed has
experienced a drastic shift in land use. This study was conducted to examine the
changes in land cover and the implied changes in land use that have occurred and
their environmental, water quality impacts. Aerial photography of the watershed
(1951, 1956, 1968, 1977, 1989, 1999, 2005, 2006, and 2009) was analyzed and
classified using the geographic information system (GIS) software. Seven land
cover classes were defined: evergreen, deciduous, bare ground, pasture/grassland,
cultivated, and residential/other development. Water quality data, including
sampling depth, water temperature, dissolved oxygen content, fecal coliform
levels, inorganic nitrogen concentrations, and turbidity, were obtained from the
South Carolina (SC) Department of Health and Environmental Control (SCDHEC) for
two stations and analyzed for trends as they relate to land cover change. From
1951 to 2009, the watershed experienced an increase of tree cover and bare ground
(+17.4 % evergreen, +62.3 % deciduous, +9.8 % bare ground) and a decrease of
pasture/grassland and cultivated land (-42.6 % pasture/grassland and -57.1 %
cultivated). From 2005 to 2009, there was an increase of 21.5 % in
residential/other development. Sampling depth ranged from 0.1 to 0.3 m. Water
temperature fluctuated corresponding to changing air temperatures, and dissolved
oxygen content fluctuated as a factor of water temperature. Inorganic nitrogen
content was higher from December to April possibly due to application of
fertilizers prior to the growing season. Turbidity and fecal coliform bacteria
levels remained relatively the same from 1962 to 2005, but a slight decline in pH
can be observed at both stations. Prior to 1938, the area consisted of single
crop cotton farms; after 1938, the farms were abandoned, leaving large bare areas
with highly eroded soil. Starting in 1938, Clemson reforested almost 30 % of the
watershed. Currently, three fourths of the watershed is forestland, with a
limited coverage of small farms and residential developments. Monitoring water
quality is essential in maintaining adequate freshwater supply. Water quality
monitoring focuses mainly on the collection of field data, but current water
quality conditions depend on the cumulative impacts of land cover change over
time.
PMID- 25124991
TI - The role of subscapularis muscle denervation in the pathogenesis of shoulder
internal rotation contracture after neonatal brachial plexus palsy: a study in a
rat model.
AB - We assessed the role of subscapularis muscle denervation in the development of
shoulder internal rotation contracture in neonatal brachial plexus injury.
Seventeen newborn rats underwent selective denervation of the subscapular muscle.
The rats were evaluated at weekly intervals to measure passive shoulder external
rotation. After 4 weeks, the animals were euthanized. The subscapularis thickness
was measured using 7.2T MRI axial images. The subscapularis muscle was then
studied grossly, and its mass was registered. The fiber area and the area of
fibrosis were measured using collagen-I inmunostained muscle sections.
Significant progressive decrease in passive shoulder external rotation was noted
with a mean loss of 58 degrees at four weeks. A significant decrease in
thickness and mass of the subscapularis muscles in the involved shoulders was
also found with a mean loss of 69%. Subscapularis muscle fiber size decreased
significantly, while the area of fibrosis remained unchanged. Our study shows
that subscapularis denervation, per se, could explain shoulder contracture after
neonatal brachial plexus injury, though its relevance compared to other
pathogenic factors needs further investigation.
PMID- 25124992
TI - Indocyanine green and fluorescence lymphangiography for sentinel lymph node
identification in cutaneous melanoma.
AB - BACKGROUND AND OBJECTIVES: Sentinel lymph node (SLN) biopsy has become the
standard method of determining regional lymph node involvement in cutaneous
melanoma. Although traditionally performed via injection of radioisotope tracers
and blue dyes, fluorescent lymphangiography with indocyanine green (ICG) is an
attractive alternative. METHODS: Fifty two consecutive patients with cutaneous
melanoma of the trunk or extremities underwent SLNB. Preoperative
lymphoscintigraphy was performed with technetium-99m sulfur colloid (TSC).
Peritumoral intradermal injection of isosulfan blue (ISB) and ICG was then
performed. Successful identification of a sentinel lymph node via each modality
was then assessed. RESULTS: A total of 77 lymph nodes were identified from the 52
patients (range 1-3). The majority of melanomas were extremity-based, superficial
spreading type, and had SLN localized to the axilla. There were no complications
related to IcG administration. Rates of SLN detection were 96.2% for TSC, 59.6%
for ISB, and 88.5% for IcG (P < 0.05 for ICG vs ISB). On univariate logistic
regression analysis, no factors were found to be associated with failure of ICG.
CONCLUSIONS: Fluorescent lymphangiography using ICG is an effective method of SLN
identification in patients with cutaneous melanoma of the trunk and extremities.
When ICG and TSC are used in combination, ISB offers no additional advantage and
may be safely omitted.
PMID- 25124993
TI - The use of decision trees and naive Bayes algorithms and trace element patterns
for controlling the authenticity of free-range-pastured hens' eggs.
AB - This article aims to evaluate 2 machine learning algorithms, decision trees and
naive Bayes (NB), for egg classification (free-range eggs compared with battery
eggs). The database used for the study consisted of 15 chemical elements (As, Ba,
Cd, Co, Cs, Cu, Fe, Mg, Mn, Mo, Pb, Se, Sr, V, and Zn) determined in 52 eggs
samples (20 free-range and 32 battery eggs) by inductively coupled plasma mass
spectrometry. Our results demonstrated that decision trees and NB associated with
the mineral contents of eggs provide a high level of accuracy (above 80% and 90%,
respectively) for classification between free-range and battery eggs and can be
used as an alternative method for adulteration evaluation.
PMID- 25124994
TI - Further evidence of the importance of RIT1 in Noonan syndrome.
AB - Noonan syndrome (NS) is an autosomal dominant disorder consisting of short
stature, short and/or webbed neck, distinctive facial features, cardiac
abnormalities, cryptorchidism, and coagulation defects. NS exhibits genetic
heterogeneity, associated with mutated genes that participate in RAS-mitogen
activated protein kinase signal transduction. Recently, a new gene (RIT1) was
discovered as the causative gene in 17 of 180 Japanese individuals who were
negative for the previously known genes for NS and were studied using exome
sequencing (four patients), followed by Sanger sequencing (13 patients). The
present study used the same technique in 70 Brazilian patients with NS and
identified six with RIT1 missense mutations. Thus, we confirm that RIT1 is
responsible for approximately 10% of the patients negative for mutations in the
previously known genes. The phenotype includes a high frequency of high birth
weight, relative macrocephaly, left ventricular hypertrophy, and ectodermal
findings, such as curly hair, hyperpigmentation, and wrinkled palms and soles.
Short stature and pectus deformity were less frequent. The majority of patients
with a RIT1 mutation did not show apparent intellectual disability. Because of
the relatively high frequency of mutations in RIT1 among patients with NS and its
occurrence in different populations, we suggest that it should be added to the
list of genes included in panels for the molecular diagnosis of NS through
targeted next-generation sequencing.
PMID- 25124995
TI - Increased expression of cystatin C and transforming growth factor beta-1 in
calcific aortic valves.
PMID- 25124996
TI - The impact of anatomical remodeling of the left atrium and pulmonary vein on the
recurrence of paroxysmal atrial fibrillation after catheter ablation.
PMID- 25124997
TI - YOUng Football Italian amateur players Remote electrocardiogram Screening with
Telemedicine (YOU FIRST) study: preliminary results.
PMID- 25124999
TI - Variability of right ventricular angiography in arrhythmogenic right ventricular
cardiomyopathy.
PMID- 25124998
TI - Circulating miR-323-3p and miR-652: candidate markers for the presence and
progression of acute coronary syndromes.
AB - BACKGROUND: The prognostic utility of circulating plasma microRNA in patients
with acute coronary syndromes (ACS) has been proposed but not yet demonstrated.
We set out to investigate circulating microRNA levels in patients incurring
recent ACS and examined associations with neurohormones, cardiac structure and
function, and survival over 5 years of follow-up. METHODS: An initial screen of
375 microRNAs was performed in 35 ACS patients and 16 healthy controls.
Candidates identified from the initial screen (miR-323-3p, miR-652, miR-27b, miR
103 and miR-208a) were validated in a further cohort of 200 patients at baseline
(~ 30 days post-ACS) and at 4 and 12 months post-ACS, and compared with 100
controls. RESULTS: In the validation cohort, significantly higher levels in
patients were replicated for miR-323-3p, miR-652 and miR-27b (10-fold, 2.3-fold
and 2.3-fold, respectively, adjusted p<0.05). Lower levels of miR-103 were not
replicated and miR-208a was undetectable. From baseline to 4 months post
admission, miR-323-3p and miR-652 remained elevated in patients compared to
controls (adjusted p<0.01), with no further change in levels between 4 and 12
months; whereas miR-27b fell to control levels by 4 months. Baseline levels of
miR-652 in the lowest tertile were significantly associated with readmission for
heart failure (log-rank p<0.001). In combination with NT-proBNP and LVEF, miR-652
significantly improved risk stratification (p<0.001). CONCLUSIONS: Our study
identifies miR-652 as a novel candidate biomarker for post-ACS prognosis beyond
existing biomarkers of LVEF and NT-proBNP. Moreover circulating miR-323-3p was
markedly elevated in patients for at least a year post-ACS and may be a stable
biomarker for ACS.
PMID- 25125000
TI - Strenuous exercise and the heart: are we not seeing the wood for the trees?
PMID- 25125002
TI - Gender differences in quality of life after PCI attenuate after a 10 year follow
up.
PMID- 25125001
TI - Reduced functionality in everyday activities of patients with self-reported heart
failure hospitalization--population-based study results.
AB - AIM: To assess daily functioning and geriatric conditions of older subjects
suffering from heart failure (HF) as compared to the general population. METHODS
AND RESULTS: The data were collected as part of the nationwide PolSenior project
(2007-2011). Of 4979 individuals (age range 65-104 years), data on self-reported
HF hospitalization were available for 4795 subjects (96%). Geriatric assessment
(GA) included functional status (ADL, Activities of Daily Living and IADL,
Instrumental ADL scales), cognitive function, mood disorders, sensory organ
impairment, falls and comorbidity. Mean age +/- SD of the study population was
73.8 +/- 6.5 years; 62% were female. The proportion of subjects with HF
hospitalizations increased from 8% in subjects aged 65-69 years up to 13% in the
age group of 85-89 years, and decreased in nonagenarians (11%). Subjects with the
HF hospitalization were older, used more drugs, and were characterized by a
higher prevalence of comorbid conditions, mood disorders, hearing impairment and
functional limitations. In logistic regression, HF hospitalization increased the
age-sex adjusted risk of disability by 40%, both in ADL and IADL. After
adjustment to other clinical and geriatric conditions, HF hospitalization
remained an independent predictor of disability in both ADL (OR=1.36, 95%CI: 1.00
1.84) and IADL (OR=1.40, 95%CI: 1.01-1.93). CONCLUSIONS: Older people who
reported HF admissions had a higher number of comorbidities and geriatric
conditions: mood disorders, hearing impairment and functional limitations.
Besides, in our study, HF hospitalization independently and significantly
increased the risk of limitations in IADL and ADL. Therefore, further studies are
needed to evaluate the benefits of GA in patients with HF.
PMID- 25125003
TI - Is acute respiratory failure requiring mechanical ventilation associated with
development of takotsubo cardiomyopathy in the critical care setting?
PMID- 25125004
TI - Androgen attenuates cardiac fibroblasts activations through modulations of
transforming growth factor-beta and angiotensin II signaling.
AB - BACKGROUND: Androgen deficiency produces heart failure, which can be ameliorated
by testosterone supplementation. Cardiac fibrosis plays a critical role in the
pathophysiology of heart failure. This study aimed to evaluate whether
testosterone can attenuate cardiac fibroblast activity through modulating
transforming growth factor (TGF)-beta and angiotensin (Ang) II signaling.
METHODS: Migration, proliferation, myofibroblast differentiation, collagen
production, and transcription signaling were evaluated in adult male rat
(weighing 300-350 g) cardiac fibroblasts with and without incubation with
testosterone (10nM) and co-administration of TGF-beta1 (10 ng/ml) or Ang II (100
nM) by cell migration analysis, proliferation assay, soluble collagen
measurement, zymographic analysis, immunofluorescence microscopy, real-time PCR
and Western blot. RESULTS: Compared to those without testosterone, testosterone
treated fibroblasts exhibited less collagen production. Testosterone-treated
fibroblasts also had less migration, proliferation, myofibroblast
differentiation, and collagen production in the presence of TGF-beta1, or had
less collagen production with Ang II. Testosterone-treated fibroblasts had
decreased phosphorylated Akt, mammalian target of rapamycin, and 4E binding
protein-1 irrespective of TGF-beta1 treatment and had increased matrix
metalloproteinase (MMP)-2 in the presence of TGF-beta1 treatment, and had
decreased phosphorylated P38 and Smad 2/3 levels in the presence of Ang II.
Cardiac fibroblasts with and without testosterone had similar mRNA and protein
expressions of total Akt and total Smad 2/3 irrespective of TGF-beta1 or Ang II
treatment. CONCLUSION: Physiological level of testosterone attenuated Akt and
Smad 2/3 phosphorylation mediated by TGF-beta1 and angiotensin II respectively,
which can result in decreased cardiac fibroblast activation and potentially
contribute to beneficial effects in heart failure.
PMID- 25125005
TI - Secondary prevention of sudden cardiac death in a 65 year untreated ALCAPA
patient.
PMID- 25125006
TI - Left ventricular or Bi-ventricular assist device? How dobutamine stress
echocardiography can untie the dilemma of right ventricular dysfunction.
PMID- 25125007
TI - Prognostic significance of mitral regurgitation in long-term all-cause mortality
in patients aged >= 80 years with acute coronary syndrome.
AB - BACKGROUND: Mitral regurgitation (MR) has been shown to be associated with a poor
prognosis in the patients with acute myocardial infarction, whether or not
percutaneous coronary intervention (PCI) is employed. However, the long-term
prognostic significance of MR in octogenarian patients with acute coronary
syndrome (ACS) remains unknown. We sought to determine the impact of MR on long
term all-cause mortality and to further reveal whether PCI could influence the
prognosis in octogenarian MR patients with ACS. METHODS: In this study, we
included a total of 353 consecutive hospitalized patients, aged >= 80 years, with
ACS during the period of 5-year follow-up. Association between MR and long-term
all-cause mortality was analyzed both in a overall cohort and in a matched cohort
developed from a propensity score analysis. RESULTS: MR was independently
associated with long-term all-cause mortality in the overall and matched cohorts
(hazard ratio (HR) 1.58, 95% CI 1.01-2.47, P=0.043; HR 1.90, 95% CI 1.15-3.13,
P=0.013). In the subgroup treated with PCI, MR also exhibited higher long-term
all-cause mortality, PCI remained an independent determinant of improving long
term survival rate by reducing the mortality by 15.1% in ACS patients with MR
aged >= 80 years. CONCLUSIONS: Our study demonstrates that MR is independently
associated with long-term all-cause mortality, and PCI is an independent
determinant for improving the long-term survival rate in the octogenarian ACS
patients with MR.
PMID- 25125008
TI - Relationship between fractional flow reserve and residual plaque volume and
clinical outcomes after optimal drug-eluting stent implantation: insight from
intravascular ultrasound volumetric analysis.
AB - BACKGROUND: The underlying cause of FFR reduction and prognostic impact of FFR
after optimal DES implantation remain unknown. The study aims were to use
intravascular ultrasound (IVUS) to investigate the mechanism responsible for
reduced fractional flow reserve (FFR) after optimal drug-eluting stent (DES)
implantation and to evaluate FFR effect on clinical outcomes after optimal
percutaneous coronary intervention with DES. METHODS: Ninety-seven patients
treated with optimal DES implantation under IVUS and pullback FFR guidance were
followed clinically (median 17.8 months). Post-stenting IVUS examination and
pullback FFR recording were performed, and angiographic and IVUS parameters
associated with reduced FFR were evaluated. The composite of major adverse
cardiac events (MACE), including cardiac death, myocardial infarction, stent
thrombosis, and target vessel revascularization, was analyzed. RESULTS:
Regression analysis showed inverse correlations between post-stent FFR and
residual plaque volume index (r=-0.40, p<0.01) and residual percent plaque volume
(r=-0.68, p<0.01) in IVUS but no correlation of minimal lesion diameter with
quantitative coronary angiography (r=0.07, p=0.50) or IVUS-derived minimal stent
area (r=0.02, p=0.84). MACE was observed in 10 patients (10.3%), and FFR after
optimal stenting was significantly lower in this group (0.86 +/- 0.04 vs 0.91 +/-
0.04, p<0.01). The optimal FFR threshold for predicting MACE was 0.90, identified
by the receiver operating characteristic curve. CONCLUSIONS: Reduced FFR after
optimal DES implantation was associated with residual plaque volume identified by
IVUS and future adverse cardiac events.
PMID- 25125009
TI - Neoatherosclerosis--a cause of late stent thrombosis?
PMID- 25125010
TI - Postconditioning or preconditioning, which should be promoted in the protection
of ischemic reperfusion injury?
PMID- 25125011
TI - Reply: Comments on hypertonic saline with furosemide for the treatment of acute
congestive heart failure: a systematic review and meta-analysis.
PMID- 25125012
TI - Edentulism associates with poor cardiovascular health. Results from the Atahualpa
Project.
PMID- 25125013
TI - Switching from ticagrelor to prasugrel: a warning.
PMID- 25125014
TI - Cerebral microemboli and neurocognitive change after carotid artery stenting with
different embolic protection devices.
AB - OBJECTIVES: Proximal cerebral protection devices have been developed as an
alternative to filter protection devices for reducing neurological complications
during carotid artery stenting (CAS). The aim of the present study was to
evaluate the frequency of silent cerebral embolism after CAS using different
cerebral embolic protection devices and the impact of silent cerebral embolism on
neurocognitive function. METHODS: One hundred consecutive patients who underwent
CAS were enrolled. The patients were randomized to either proximal balloon
occlusion or filter protection. Neurocognitive tests were performed before and
six months after CAS. Cerebral embolisms were evaluated with diffusion-weighted
magnetic resonance imaging (DW-MRI). RESULTS: The number and volume of new
ischemic lesions found with DW-MRI were higher in the filter protection group
than in the proximal balloon occlusion group. According to our definition, nine
(21%) patients in the balloon occlusion group and 16 (36%) patients in the filter
protection group showed neurocognitive decline, and ten (23%) patients in the
balloon occlusion group and four (9%) patients in the filter protection group
showed neurocognitive improvement (NS). Regarding the group of patients with new
cerebral ischemic lesions on DW-MRI, neurocognitive decline occurred in 14 (31%)
of 45 patients with DW-MRI lesions and 11 (26%) of 43 patients without DW-MRI
lesions (NS). CONCLUSION: Neurocognitive outcome after CAS is unpredictable; both
neurocognitive decline and improvement can occur. In this study, the proximal
balloon occlusion system significantly decreased cerebral microemboli during CAS
compared to filter protection. Cerebral microembolism was not found to be
associated with neurocognitive decline.
PMID- 25125015
TI - Incidence and clinical characteristics of takotsubo cardiomyopathy post
aneurysmal subarachnoid hemorrhage.
PMID- 25125016
TI - Depression among cardiovascular patients living in a Middle Eastern country-
preliminary findings from a cross-sectional survey.
PMID- 25125017
TI - Glucagon-like peptide-1 levels on admission for acute myocardial infarction with
or without acute hyperglycemia.
PMID- 25125018
TI - Low plasma renin level is associated with the occurrence of angiographic radial
artery spasm in patients undergoing transradial coronary procedures.
PMID- 25125019
TI - Validation of a risk scoring model for prediction of acute cardiac complications
in chest pain patients presenting to the Emergency Department.
PMID- 25125020
TI - Chronic obstructive pulmonary disease and hypertrophic obstructive
cardiomyopathy: two antagonistic obstructions.
PMID- 25125021
TI - Inappropriate implantable cardioverter-defibrillator shocks and signal jammers:
first report of a new interference.
PMID- 25125022
TI - Quantifying subtle changes in cardiovascular mechanics in acromegaly: a Doppler
myocardial imaging study.
AB - AIM OF THE STUDY: To describe morphological and functional cardiovascular changes
in acromegaly (ACM) patients, as well as to investigate the ability of Doppler
based myocardial deformation imaging (DMI) to characterize subtle dysfunction in
ACM. METHODS: 69 patients (pts) with ACM (mean age 47 +/- 10 years, 27 men) and
31 controls (mean age 43 +/- 16 years, matched for age and gender) were
recruited. Standard echocardiography and DMI data were obtained for all patients.
Peak systolic longitudinal strain values (S) were determined for the left and
right ventricles. Radial S was measured at the level of the mid inferolateral
segment. Using a high-resolution echo-tracking system, the main indices of
arterial stiffness were measured. RESULTS: Of the ACM subjects, 57 had active
disease (group A), and 12 controlled ACM (group B). All pts with ACM presented
structural changes: a higher LV indexed mass (112 +/- 36, 118 +/- 23 vs 74 +/- 18
g/m(2), p < 0.001) and a higher relative wall thickness (0.45 +/- 0.09, 0.50 +/-
0.07 vs 0.40 +/- 0.07, p = 0.003) compared to controls. Also, ACM pts had
functional changes: reduced LV ejection fraction (57 +/- 5, 55 +/- 5 vs 64 +/-
4%, p < 0.001) and altered diastolic function (E/A 1.0 +/- 0.4, 1.1 +/- 0.1 vs
1.3 +/- 0.3, p = 0.005) compared to controls. Both longitudinal and radial LV S
values were lower in ACM compared to controls: -16.5 +/- 3.5, -16.8 +/- 4.3 vs
21.5 +/- 3.8%, p < 0.001 for longitudinal and 38.3 +/- 12.3, 35.6 +/- 11.8 vs
52.2 +/- 11.7%, p = 0.002 for radial strain. CONCLUSIONS: ACM pts present LV
concentric hypertrophy and LV systolic and diastolic dysfunction, even in
controlled disease. Altered global LV systolic function appears to be due both to
longitudinal and radial dysfunction.
PMID- 25125023
TI - A review of the effects of Nigella sativa L. and its constituent, thymoquinone,
in metabolic syndrome.
AB - BACKGROUND: Metabolic syndrome is an important risk factor for cardiovascular
disease (CVD) occurrence and mortality. CVDs are leading cause of death
worldwide. Recently, there has been an increasing interest in the use of herbal
medicines with more efficiency and minimal undesirable effects than chemical
drugs for a variety of disorders including CVD. Nigella sativa and its active
constituent, thymoquinone, have been documented to exhibit antidiabetic,
antiobesity, hypotensive and hypolipidemic properties. AIM: In this review, we
discussed the most relevant articles to find out the role of N. sativa in
different components of metabolic syndrome and CVD risk factors including high
blood pressure, obesity, dyslipidemia and high blood glucose. CONCLUSIONS: This
review suggests a potential role of N. sativa and TQ in the management of
metabolic syndrome, however more studies should be conducted to evaluate their
effectiveness.
PMID- 25125024
TI - Psychosocial, behavioural, pedagogical, and nutritional proposals about how to
encourage eating a healthy breakfast.
AB - BACKGROUND: Even if more and more evidences have highlighted the importance of
breakfast in the growth and development of children, from 10 to 30% of US and
European children and adolescents regularly skip breakfast. Thus, there is still
a lot to be done before breakfast becomes a daily habit. The aim of this paper is
to try and understand how it is possible to overcome the real or imaginary
difficulties associated with skipping breakfast by psychosocial, behavioural,
pedagogical and nutritional proposals. DISCUSSION: Schools are the best context
where perform healthy interventions because it is here that children learn about
the importance of good health at an age when the school still plays a major role
in their education. Some school interventions, based on solid theories as the
Self Determination Theory and the Behaviour Analysis, have been implemented in
the last years to promote health behaviour such as intake of fruit and vegetables
and physical activities. Cognitive behaviour therapy is the most closely
monitored type of treatment/cure for obesity in randomised controlled trials.
Moreover some associations such as the National Association of Food Science
Specialists have drawn an own method to encourage food education at school and
promote the importance of prevention. These projects could be used as starting
point to perform interventions focus on breakfast. SUMMARY: Increase the
consumption of breakfast between children is very important. Efforts should be
done to drawn new school projects based on scientific-evidences.
PMID- 25125026
TI - Glial Asthenia and Functional Paralysis: A New Perspective on Neurodegeneration
and Alzheimer's Disease.
AB - Neuroglia are represented by several population of cells heterogeneous in
structure and function that provide for the homeostasis of the brain and the
spinal cord. Neuroglial cells are also central for neuroprotection and defence of
the central nervous system against exo- and endogenous insults. At the early
stages of neurodegenerative diseases including Alzheimer's disease neuroglial
cells become asthenic and lose some of their homeostatic, neuroprotective, and
defensive capabilities. Astroglial reactivity, for example, correlates with
preservation of cognitive function in patients with mild cognitive impairment and
prodromal Alzheimer's disease. Here, we overview the experimental data indicating
glial paralysis in neurodegeneration and argue that loss of glial function is
fundamental for defining the progression of neurodegenerative diseases.
PMID- 25125025
TI - Metabolism-related pharmacokinetic drug-drug interactions with tyrosine kinase
inhibitors: current understanding, challenges and recommendations.
AB - Drug-drug interactions (DDIs) occur when a patient's response to the drug is
modified by administration or co-exposure to another drug. The main cytochrome
P450 (CYP) enzyme, CYP3A4, is implicated in the metabolism of almost all of the
tyrosine kinase inhibitors (TKIs). Therefore, there is a substantial potential
for interaction between TKIs and other drugs that modulate the activity of this
metabolic pathway. Cancer patients are susceptible to DDIs as they receive many
medications, either for supportive care or for treatment of toxicity. Differences
in DDI outcomes are generally negligible because of the wide therapeutic window
of common drugs. However for anticancer agents, serious clinical consequences may
occur from small changes in drug metabolism and pharmacokinetics. Therefore, the
objective of this review is to highlight the current understanding of DDIs among
TKIs, with a focus on metabolism, as well as to identify challenges in the
prediction of DDIs and provide recommendations.
PMID- 25125027
TI - The spatiotemporal segregation of GAD forms defines distinct GABA signaling
functions in the developing mouse olfactory system and provides novel insights
into the origin and migration of GnRH neurons.
AB - Gamma-aminobutyric acid (GABA) has a dual role as an inhibitory neurotransmitter
in the adult central nervous system (CNS) and as a signaling molecule exerting
largely excitatory actions during development. The rate-limiting step of GABA
synthesis is catalyzed by two glutamic acid decarboxylase isoforms GAD65 and
GAD67 coexpressed in the GABAergic neurons of the CNS. Here we report that the
two GADs show virtually nonoverlapping expression patterns consistent with
distinct roles in the developing peripheral olfactory system. GAD65 is expressed
exclusively in undifferentiated neuronal progenitors confined to the
proliferative zones of the sensory vomeronasal and olfactory epithelia In
contrast GAD67 is expressed in a subregion of the nonsensory
epithelium/vomeronasal organ epithelium containing the putative Gonadotropin
releasing hormone (GnRH) progenitors and GnRH neurons migrating from this region
through the frontonasal mesenchyme into the basal forebrain. Only GAD67+, but not
GAD65+ cells accumulate detectable GABA. We further demonstrate that GAD67 and
its embryonic splice variant embryonic GAD (EGAD) concomitant with GnRH are
dynamically regulated during GnRH neuronal migration in vivo and in two
immortalized cell lines representing migratory (GN11) and postmigratory (GT1-7)
stage GnRH neurons, respectively. Analysis of GAD65/67 single and double knock
out embryos revealed that the two GADs play complementary (inhibitory) roles in
GnRH migration ultimately modulating the speed and/or direction of GnRH
migration. Our results also suggest that GAD65 and GAD67/EGAD characterized by
distinct subcellular localization and kinetics have disparate functions during
olfactory system development mediating proliferative and migratory responses
putatively through specific subcellular GABA pools.
PMID- 25125028
TI - A dual-task design of corrosion-controlling and osteo-compatible
hexamethylenediaminetetrakis- (methylene phosphonic acid) (HDTMPA) coating on
magnesium for biodegradable bone implants application.
AB - Magnesium as well as its alloys appears increasingly as a revolutionary bio-metal
for biodegradable implants application but the biggest challenges exist in its
too fast bio-corrosion/degradation. Both corrosion-controllable and bio
compatible Mg-based bio-metal is highly desirable in clinic. In present work,
hexamethylenediaminetetrakis (methylenephosphonic acid) [HDTMPA, (H2 O3 P-CH2 )2
N-(CH2 )6 -N-(CH2 -PO3 H2 )2 ], as a natural and bioactive organic substance, was
covalently immobilized and chelating-deposited onto Mg surface by means of
chemical conversion process and dip-coating method, to fullfill dual-task
performance of corrosion-protective and osteo-compatible functionalities. The
chemical grafting of HDTMPA molecules, by participation of functional groups on
pretreated Mg surface, ensured a firmly anchored base layer, and then sub
sequential chelating reactions of HDTMPA molecules guaranteed a homogenous and
dense HDTMPA coating deposition on Mg substrate. Electrochemical corrosion and
immersion degradation results reveal that the HDTMPA coated Mg provides a
significantly better controlled bio-corrosion/degradation behavior in phosphate
buffer saline solution as compared with untreated Mg from perspective of clinic
requirement. Moreover, the HDTMPA coated Mg exhibits osteo-compatible in that it
induces not only bioactivity of bone-like apatite precipitation but also promotes
osteoblast cells adhesion and proliferation. Our well-controlled biodegradable
and biocompatible HDTMPA modified Mg might bode well for next generation bone
implant application.
PMID- 25125029
TI - Functionalized fullerene (C60) as a potential nanomediator in the fabrication of
highly sensitive biosensors.
AB - Designing a biosensor for versatile biomedical applications is a sophisticated
task and how dedicatedly functionalized fullerene (C60) can perform on this stage
is a challenge for today and tomorrow's nanoscience and nanotechnology. Since the
invention of biosensor, many ideas and methods have been invested to upgrade the
functionality of biosensors. Due to special physicochemical characteristics, the
novel carbon material "fullerene" adds a new dimension to the construction of
highly sensitive biosensors. The prominent aspects of fullerene explain its
outstanding performance in biosensing devices as a mediator, e.g. fullerene in
organic solvents exhibits five stages of reversible oxidation/reduction, and
hence fullerene can work either as an electrophile or nucleophile. Fullerene is
stable and its spherical structure produces an angle strain which allows it to
undergo characteristic reactions of addition to double bonds (hybridization which
turns from sp(2) to sp(3)). Research activities are being conducted worldwide to
invent a variety of methods of fullerene functionalization with a purpose of
incorporating it effectively in biosensor devices. The different types of
functionalization methods include modification of fullerene into water soluble
derivatives and conjugation with enzymes and/or other biomolecules, e.g. urease,
glucose oxidase, hemoglobin, myoglobin (Mb), conjugation with metals e.g. gold
(Au), chitosan (CS), ferrocene (Fc), etc. to enhance the sensitivity of
biosensors. The state-of-the-art research on fullerene functionalization and its
application in sensor devices has proven that fullerene can be implemented
successfully in preparing biosensors to detect glucose level in blood serum, urea
level in urine solution, hemoglobin, immunoglobulin, glutathione in real sample
for pathological purpose, to identify doping abuse, to analyze pharmaceutical
preparation and even to detect cancer and tumor cells at an earlier stage.
Employing fullerene-metal matrix for the detection of tumor and cancer cells is
also possible by the inclusion of fullerene in single-walled carbon nanotubes
(SWCNTs) known as peapods as well as in double-walled carbon nanotubes (DWCNTs),
to augment the effectiveness of biosensors. This review discusses various
approaches that have been reported for functionalizing fullerene (C60)
derivatives and their application in different types of biosensor fabrication.
PMID- 25125031
TI - [A rare cause of cyanosis in a pre-term infant].
PMID- 25125030
TI - [Thrombopenia and the nature of the microorganism in infected critically ill
children].
AB - BACKGROUND: Thrombopenia is correlated with sepsis and mortality in pediatric
intensive care units. The purpose of this study was to find an association
between thrombopenia and the microorganism type to guide the choice of empiric
antibiotic therapy in infected critically ill children. MATERIALS AND METHODS: We
conducted a prospective descriptive study, including all newborns, infants, and
children admitted to a pediatric surgical intensive care unit from 1st January to
31st December 2009. We identified patients who developed an infection and/or
thrombopenia (platelet count less than 100,000/mm(3)) during hospitalization.
RESULTS: One hundred ninety-seven patients were included (57 newborns, 41
infants, 99 children). Ninety patients developed 100 infectious episodes during
the study period. Of the 57 newborns enrolled in the study, 31 (54%) developed 37
infections. Seventy-six microorganisms (55 Gram-negative bacilli [GNB], 17 Gram
positive cocci, two Gram-negative cocci, two fungal pathogens) were identified
during 65 infectious episodes in 55 patients. Thirty-four episodes of
thrombopenia were observed in 30 patients. Thrombopenia was observed only in
infected patients (P<0.001). Thrombopenia was associated with infections caused
by GNB (26/28 vs 20/37, P=0.001) and by Klebsiella (16/28 vs 6/37, P=0.001) and
may be associated with infections caused by GNB producing extended-spectrum beta
lactamases (P=0.07). Gram-positive cocci infections were correlated to the non
occurrence of thrombopenia (P=0.02). Postoperative peritonitis was also
significantly associated with thrombopenia (P=0.03). The mortality rate in our
patients was 12.7% (22.8% in neonates). There was an association between
thrombopenia and death in univariate analysis (11/25 vs 19/172, P<0.001).
Multivariate logistic regression analysis did not confirm thrombopenia as an
independent predictive factor of mortality in children. CONCLUSION: Because of
the relatively high proportion of resistant GNB, an empiric antibiotic therapy
combining a carbapenem and an aminoglycoside may be indicated in infected
critically ill children developing thrombopenia.
PMID- 25125032
TI - [Efficacy and safety of intravenous immunoglobulins in the management of neonatal
hyperbilirubinemia due to ABO incompatibility: a meta-analysis].
AB - OBJECTIVES: ABO fetomaternal red blood cell incompatibility (ABO FMI) induces an
immune hemolysis after fetal transfer of hemolyzing maternal anti-A or anti-B.
ABO hemolytic disease (ABO HD) remains the most frequent cause of severe and
early jaundice in newborns. High levels of unconjugated hyperbilirubinemia may
induce acute and chronic neurological complications. Severe hyperbilirubinemia
can be prevented by first-line phototherapy (PT) treatment, but exchange
transfusion (ET) is required if treatment is not effective, even if ET is linked
with high hemodynamic, infectious, gastrointestinal, and/or biological morbidity.
Intravenous human polyclonal immunoglobulins (IVIg) have been proposed in
concomitant use with PT in order to avoid the requirement for ET in ABO FMI.
METHODS: Electronic databases of all published clinical trials in neonatal
hyperbilirubinemia due to ABO incompatibility were systematically queried for
randomized controlled clinical trials comparing PT alone to PT associated with
IVIg based on the requirement for ET. Duration of PT and adverse events were
optional criteria. A meta-analysis of the selected data was performed on six
selected trials out of 28 found. RESULTS: IVIg doses ranged from 0.5 to 1.5 g/Kg
in one to three administrations. Requirement for ET was lower in the IgIV+PT
group, with a relative risk of 0.27 [CI 95% 0.17-0.42; P<0.00001], expressed as a
number needed to treat of five neonates to avoid one ET. The mean duration of PT
was 4 days in the PT group and association of PT with IVIg significantly reduced
the duration of PT treatment by 0.84 days. The tolerance of the IVIg and PT
association was good with no reported cases of ulcerative enterocolitis in 265
treated newborns. CONCLUSION: IVIG associated with PT reduces the need for ET and
the duration of PT in newborns with hyperbilirubinemia due to ABO hemolytic
disease. Their efficacy and good tolerance prompt consideration of IVIg as a
therapeutic adjuvant to PT in severe hemolytic hyperbilirubinemia due to ABO
incompatibility.
PMID- 25125033
TI - [Lacidipine efficacy and safety for high blood pressure treatment in pediatric
oncohematology].
AB - In adults, lacidipine seems to have no CYP3A4-inhibiting action. This particular
characteristic makes it advantageous when combined with drugs metabolized by
CYP3A4, such as cyclosporine. Until now, no data on the efficacy or safety of
this calcium antagonist have been available in children. Thirty-nine hypertensive
children (age: 0.13-14 years) receiving lacidipine in oncohematology for a mean
of 75 days were included in this retrospective study. The causes of high blood
pressure were renal tumor (n=7), catecholamine-secreting tumor (n=4), corticoid
treatment (n=5), and cyclosporine treatment (n=23). An initial dosage of 0.05
mg/kg/day was sufficient for 41% of the patients. The remaining patients needed
to increase the dosage, by steps of 0.03 mg/kg/day, until reaching an average
effective dosage of 0.1 mg/kg/day. Lacidipine significantly decreased blood
pressure by 30 (+/-14) mmHg for systolic blood pressure and by 26 (+/-13) mmHg
for diastolic blood pressure. A medication plan with twice-daily administration
was not significantly more effective than a single administration per day.
Lacidipine was well tolerated, and no toxicity-related withdrawal of treatment
occurred. For 22 patients treated with both cyclosporine and lacidipine, renal
function was not disturbed over time, suggesting its preservation by lacidipine.
No significant increase in cyclosporine blood concentration was detected.
Lacidipine seems to be an effective calcium antagonist in pediatric
oncohematology, is well tolerated, has a kidney-protector effect and no drug
interaction when combined with cyclosporine.
PMID- 25125034
TI - [Lactic acidosis in a child with acute severe asthma].
AB - Lactic acidosis is a recognized event in adult patients with acute severe asthma
(ASA). Only a few cases have been reported in children. Hereinafter is reported
the case of a 2-year-old girl hospitalized in the pediatric intensive care unit
for ASA, which was treated with high-flow oxygen therapy and intravenous
methylprednisolone and salbutamol. During hospitalization, she had metabolic
acidosis with a 7.29 pH, a 26mmHg hypocapnia, and a decrease in bicarbonates to
12 mmol/L. The anion gap was increased to 20 mmol/L and lactates to 8 mmol/L. The
work-up for a congenital metabolic disease was normal. Progression was propitious
with spontaneous improvement of lactic acidosis, and the child was discharged
from the intensive care unit after 72 h. The origin of lactic acidosis during ASA
seems to be multifactorial. Although its recovery can be spontaneous, it is
important to know how to identify it because it can worsen respiratory symptoms
and can lead to incongruous therapeutic escalation.
PMID- 25125036
TI - A silenced spring?
PMID- 25125035
TI - A post hoc analysis of subgroup outcomes and creatinine in the phase III clinical
trial (EMPOWER) of dexpramipexole in ALS.
AB - Our objective was to compare the phase II and phase III (EMPOWER) studies of
dexpramipexole in ALS and evaluate potential EMPOWER responder subgroups and
biomarkers based on significant inter-study population differences. In a post hoc
analysis, we compared the baseline population characteristics of both
dexpramipexole studies and analyzed EMPOWER efficacy outcomes and laboratory
measures in subgroups defined by significant inter-study differences. Results
showed that, compared with phase II, the proportion of El Escorial criteria (EEC)
definite participants decreased (p = 0.005), riluzole use increased (p = 0.002),
and mean symptom duration increased (p = 0.037) significantly in EMPOWER.
Baseline creatinine (p < 0.001) and on-study creatinine change (p < 0.001)
correlated significantly with ALSFRS-R in EMPOWER. In the EMPOWER subgroup
defined by EEC-definite ALS, riluzole use, and < median symptom duration (15.3
months), dexpramipexole-treated participants had reduced ALSFRS-R slope decline
(p = 0.015), decreased mortality (p = 0.011), and reduced creatinine loss (p =
0.003). In conclusion, significant differences existed between the phase II and
EMPOWER study populations in ALS clinical trials of dexpramipexole. In a post hoc
analysis of EMPOWER subgroups defined by these differences, potential clinical
benefits of dexpramipexole were identified in the subgroup of riluzole-treated,
short-symptom duration, EEC-definite ALS participants. Creatinine loss correlated
with disease progression and was reduced in dexpramipexole-treated participants,
suggesting it as a candidate biomarker.
PMID- 25125038
TI - Biofouling ecology as a means to better understand membrane biofouling.
AB - Despite more than a decade of worldwide research on membrane fouling in membrane
bioreactors, many questions remain to be answered. Biofouling, which is referred
to as the unwanted deposition and growth of biofilms, remains the main problem.
Due to its complexity, most of the existing anti-biofouling strategies are not
completely successful. To unravel this complexity and finally to developed well
adapted control strategies, a microbial-based description of the biofouling
development is needed. Therefore, in this review, the biofouling formation will
be described as a typical biofilm formation in five steps including the formation
of a conditioning film, the bacterial attachment, the production of extracellular
polymeric substances, the biofilm maturation, and the bacterial detachment.
Moreover, important processes such as hydrodynamics and bacterial communication
or quorum sensing will be taken into account. It is finally discussed whether
biofouling formation is an active or inactive biofilm process together with
suggestion for further research.
PMID- 25125037
TI - Degradation of off-gas toluene in continuous pyrite Fenton system.
AB - Degradation of off-gas toluene from a toluene reservoir and a soil vapor
extraction (SVE) process was investigated in a continuous pyrite Fenton system.
The removal of off-gas toluene from the toluene reservoir was >95% by 8h in the
pyrite Fenton system, while it was ~97 % by 3h in classic Fenton system and then
rapidly decreased to initial level by 8h. Continuous consumption of low Fe(II)
concentration dissolved from pyrite surface (0.05-0.11 mM) was observed in the
pyrite Fenton system, which can lead to the effective and successful removal of
the gas-phase toluene due to stable production of OH radical (OH). Inhibitor and
spectroscopic test results showed that OH was a dominant radical that degraded
gas-phase toluene during the reaction. Off-gas toluene from the SVE process was
removed by 96% in the pyrite Fenton system, and remnant toluene from rebounding
effect was treated by 99%. Main transformation products from toluene oxidation
were benzoic acid (31.4%) and CO2 (38.8%) at 4h, while traces of benzyl alcohol
(1.3%) and benzaldehyde (0.7%) were observed. Maximum operation time of
continuous pyrite Fenton system was estimated to be 56-61 d and its optimal
operation time achieving emission standard was 28.9 d.
PMID- 25125039
TI - Escherichia coli W shows fast, highly oxidative sucrose metabolism and low
acetate formation.
AB - Sugarcane is the most efficient large-scale crop capable of supplying sufficient
carbon substrate, in the form of sucrose, needed during fermentative feedstock
production. However, sucrose metabolism in Escherichia coli is not well
understood because the two most common strains, E. coli K-12 and B, do not grow
on sucrose. Here, using a sucrose utilizing strain, E. coli W, we undertake an in
depth comparison of sucrose and glucose metabolism including growth kinetics,
metabolite profiling, microarray-based transcriptome analysis, labelling-based
proteomic analysis and (13)C-fluxomics. While E. coli W grew comparably well on
sucrose and glucose integration of the omics, datasets showed that during growth
on each carbon source, metabolism was distinct. The metabolism was generally
derepressed on sucrose, and significant flux rearrangements were observed in
central carbon metabolism. These included a reduction in the flux of the
oxidative pentose phosphate pathway branch, an increase in the tricarboxylic acid
cycle flux and a reduction in the glyoxylate shunt flux due to the
dephosphorylation of isocitrate dehydrogenase. But unlike growth on other sugars
that induce cAMP-dependent Crp regulation, the phosphoenol-pyruvate-glyoxylate
cycle was not active on sucrose. Lower acetate accumulation was also observed in
sucrose compared to glucose cultures. This was linked to induction of the acetate
catabolic genes actP and acs and independent of the glyoxylic shunt. Overall, the
cells stayed highly oxidative. In summary, sucrose metabolism was fast, efficient
and led to low acetate accumulation making it an ideal carbon source for
industrial fermentation with E. coli W.
PMID- 25125040
TI - Cellular fatty acid profile and H(+)-ATPase activity to assess acid tolerance of
Bacillus sp. for potential probiotic functional attributes.
AB - The present study has been focused widely on comparative account of probiotic
qualities of Bacillus spp. for safer usage. Initially, 170 heat resistant flora
were isolated and selected for non-pathogenic cultures devoid of cytK, hblD, and
nhe1 virulence genes. Subsequently, through biochemical tests along with 16S rRNA
gene sequencing and fatty acid profiling, the cultures were identified as
Bacillus megaterium (AR-S4), Bacillus subtilis (HR-S1), Bacillus licheniformis
(Csm1-1a and HN-S1), and Bacillus flexus (CDM4-3c and CDM3-1). The selected
cultures showed 70-80 % survival under simulated gastrointestinal condition which
was also confirmed through H(+)-ATPase production. The amount of H(+)-ATPase
increased by more than 2-fold when grown at pH 2 which support for the acid
tolerance ability of Bacillus isolates. The study also examined the influence of
acidic pH on cellular fatty acid composition of Bacillus spp. A remarkable shift
in the fatty acid profile was observed at acidic pH through an increased amount
of even numbered fatty acid (C16 and C18) in comparison with odd numbered (C15
and C17). Additionally, the cultures exhibited various probiotic functional
properties. Overall, the study increases our understanding of Bacillus spp. and
will allow both industries and consumers to choose for well-defined probiotic
with possible health benefits.
PMID- 25125041
TI - Differential contributions of two SARP family regulatory genes to indigoidine
biosynthesis in Streptomyces lavendulae FRI-5.
AB - The Streptomyces antibiotic regulatory protein (SARP) family regulators have been
shown to control the production of secondary metabolites in many Streptomyces
species as the most downstream regulators in the regulatory cascade. Streptomyces
lavendulae FRI-5 produces a blue pigment (indigoidine) together with two types of
antibiotics: D-cycloserine and the nucleoside antibiotics. The production of
these secondary metabolites is governed by a signaling system consisting of a
gamma-butyrolactone, IM-2 [(2R,3R,1'R)-2-1'-hydroxybutyl-3-hydroxymethyl-gamma
butanolide], and its cognate receptor, FarA. Here, we characterized two
regulatory genes of the SARP family, farR3 and farR4, which are tandemly located
in the proximal region of farA. farR3 is transcribed both as a monocistronic RNA
and as a bicistronic farR4-farR3 mRNA, and the expression profile is tightly
controlled by the IM-2/FarA system. Loss of farR3 delayed and decreased the
production of indigoidine without any changes in the transcriptional profile of
other far regulatory genes, indicating that FarR3 positively controls the
biosynthesis of indigoidine and is positioned in the downstream region of the IM
2/FarA signaling system. Meanwhile, loss of farR4 induced the early production of
IM-2 by increasing transcription of an IM-2 biosynthetic gene, farX, indicating
that FarR4 negatively controls the biosynthesis of IM-2. Thus, our results
suggested differential contributions of the SARP family regulators to the
regulation of secondary metabolism in S. lavendulae FRI-5. This is the first
report to show that an SARP family regulator is involved in the biosynthesis of a
signaling molecule functioning at the most upstream region of the regulatory
cascade for Streptomyces secondary metabolism.
PMID- 25125042
TI - C7-prenylation of tryptophanyl and O-prenylation of tyrosyl residues in
dipeptides by an Aspergillus terreus prenyltransferase.
AB - During our search for novel prenyltransferases, a putative gene ATEG_04218 from
Aspergillus terreus raised our attention and was therefore amplified from strain
DSM 1958 and expressed in Escherichia coli. Biochemical investigations with the
purified recombinant protein and different aromatic substrates in the presence of
dimethylallyl diphosphate revealed the acceptance of all the tested tryptophan
containing cyclic dipeptides. Structure elucidation of the main enzyme products
by NMR and MS analyses confirmed the attachment of the prenyl moiety to C-7 of
the indole ring, proving the identification of a cyclic dipeptide C7
prenyltransferase (CdpC7PT). For some substrates, reversely C3- or N1-prenylated
derivatives were identified as minor products. In comparison to the known
tryptophan-containing cyclic dipeptide C7-prenyltransferase CTrpPT from
Aspergillus oryzae, CdpC7PT showed a much higher substrate flexibility. It also
accepted cyclo-L-Tyr-L-Tyr as substrate and catalyzed an O-prenylation at the
tyrosyl residue, providing the first example from the dimethylallyltryptophan
synthase (DMATS) superfamily with an O-prenyltransferase activity towards
dipeptides. Furthermore, products with both C7-prenyl at tryptophanyl and O
prenyl at tyrosyl residue were detected in the reaction mixture of cyclo-L-Trp-L
Tyr. Determination of the kinetic parameters proved that (S)-benzodiazepinedione
consisting of a tryptophanyl and an anthranilyl moiety was accepted as the best
substrate with a K M value of 204.1 MUM and a turnover number of 0.125 s(-1).
Cyclo-L-Tyr-L-Tyr was accepted with a K M value of 1,411.3 MUM and a turnover
number of 0.012 s(-1).
PMID- 25125043
TI - Two-photon-induced fluorescence in new pi-expanded diketopyrrolopyrroles.
AB - Structurally unique pi-expanded diketopyrrolopyrroles (EDPP) were designed and
synthesized. Strategic placement of a fluorene scaffold at the periphery of a
diketopyrrolopyrrole through tandem Friedel-Crafts-dehydration reactions resulted
in dyes with supreme solubility. The structure of the dyes was confirmed by X-ray
crystallography verifying a nearly flattened arrangement of the ten fused rings.
Despite the extended ring system, the dye still preserved good solubility and was
further functionalized by using Pd-catalyzed coupling reactions, such as the
Buchwald-Hartwig amination. Photophysical studies of these new functional dyes
revealed that they possess enhanced properties when compared with expanded DPPs
in terms of two-photon absorption cross-section. It is further demonstrated that
in addition to the initial diacetals, the final electrophilic cyclization step
can also be applied to diketones. By placing two amine groups at peripheral
positions of the resulting dyes, values of two-photon absorption cross-section on
the level of 2000 GM around 1000 nm were achieved, which in combination with high
fluorescence quantum yield (Phifl ), generated a two-photon brightness of
approximately 1600 GM. These characteristics in combination with strong red
emission (665 nm) make these new pi-expanded diketopyrrolopyrroles of major
promise as two-photon dyes for bioimaging applications. Finally, the
corresponding N-alkylated DPPs displayed a solid-state fluorescence.
PMID- 25125044
TI - An enhanced photocatalytic response of nanometric TiO2 wrapping of Au
nanoparticles for eco-friendly water applications.
AB - We propose a ground-breaking approach by an upside-down vision of the Au/TiO2
nano-system in order to obtain an enhanced photocatalytic response. The system
was synthesized by wrapping Au nanoparticles (~8 nm mean diameter) with a thin
layer of TiO2 (~4 nm thick). The novel idea of embedding Au nanoparticles with
titanium dioxide takes advantage of the presence of metal nanoparticles, in terms
of electron trapping, without losing any of the TiO2 exposed surface, so as to
favor the photocatalytic performance of titanium dioxide. A complete structural
characterization was made by scanning electron microscopy, transmission electron
microscopy and X-ray diffraction. The remarkable photocatalytic performance
together with the stability of the nano-system was demonstrated by degradation of
the methylene blue dye in water. The non-toxicity of the nano-system was
established by testing the effect of the material on the reproductive cycle of
Mytilus galloprovincialis in an aquatic environment. The originally synthesized
material was also compared to conventional TiO2 with Au nanoparticles on top. The
latter system showed a dispersion of Au nanoparticles in the liquid environment,
due to their instability in the aqueous solution that clearly represents an
environmental contamination issue. Thus, the results show that nanometric TiO2
wrapping of Au nanoparticles has great potential in eco-friendly water/wastewater
purification.
PMID- 25125045
TI - In vitro assessment of the direct effect of laquinimod on basic functions of
human neural stem cells and oligodendrocyte progenitor cells.
AB - Laquinimod is an orally active immunomodulatory small molecule that has shown
clear clinical benefit in trials for relapsing-remitting multiple sclerosis and
in experimental rodent models that emulate multiple sclerosis (MS). Studies in
healthy mice, and in mice with experimental autoimmune encephalomyelitis, have
demonstrated that laquinimod is capable of entering the central nervous system.
It is therefore important to determine if laquinimod is capable of a direct
influence on basic functions of neural stem cells (NSC) or oligodendrocyte
progenitor cells (OPC)--cells critical for myelin repair in MS. In order to
address this question, a series of experiments was conducted to determine the
effect of exogenous laquinimod on viability, proliferation, migration and
differentiation of human NSC and OPC in vitro. These data show, for the first
time in cells of human origin, that direct, short-term interaction between
laquinimod and NSC or OPC, in an isolated in vitro setting, is not detrimental to
the basic cellular function of these cells.
PMID- 25125046
TI - Longitudinally extensive optic neuritis in neuromyelitis optica spectrum
disorder.
AB - BACKGROUND: Neuomyelitis optica, sarcoid, and multiple sclerosis can all cause
optic neuritis. Further means of distinguishing the causes of optic neuritis
among these etiologies would be valuable for the clinician. METHODS: This is a
retrospective, cohort study from a single university based hospital and neuro
ophthalmology clinic. Blinded interpretation of orbit MRIs was performed on
patients with acute optic neuritis from multiple sclerosis (n=25), sarcoid (n=5)
and neuromyelitis optica spectrum disorder (n=6). RESULTS: A length of >40 mm
anterior visual pathway enhancement distinguished neuromyelitis optica spectrum
disorder from multiple sclerosis (p=0.0376). No statistically significant
differences were found for presence of pain or papillitis, however there was a
trend for bilateral involvement and chiasmal involvement in neuromyelitis optica
spectrum disorder compared to multiple sclerosis. CONCLUSIONS: In acute optic
neuritis, enhancing anterior visual pathway lesion length >40 mm helps
differentiate neuromyelitis optica spectrum disorder from multiple sclerosis.
This degree of involvement can be considered longitudinally extensive optic
neuritis. Further characterization is necessary as this degree of enhancement
occurs in other clinical syndromes besides neuromyelitis optica.
PMID- 25125047
TI - Does early verbal fluency decline after STN implantation predict long-term
cognitive outcome after STN-DBS in Parkinson's disease?
AB - BACKGROUNDS: An early and transient verbal fluency (VF) decline and impairment in
frontal executive function, suggesting a cognitive microlesion effect may
influence the cognitive repercussions related to subthalamic nucleus deep brain
stimulation (STN-DBS). METHODS: Neuropsychological tests including semantic and
phonemic verbal fluency were administered both before surgery (baseline), the
third day after surgery (T3), at six months (T180), and at an endpoint multiple
years after surgery (Tyears). RESULTS: Twenty-four patients (mean age, 63.5 +/-
9.5 years; mean disease duration, 12 +/- 5.8 years) were included. Both semantic
and phonemic VF decreased significantly in the acute post-operative period (44.4
+/- 28.2% and 34.3 +/- 33.4%, respectively) and remained low at 6 months compared
to pre-operative levels (decrease of 3.4 +/- 47.8% and 10.8 +/- 32.1%) (P <
0.05). Regression analysis showed phonemic VF to be an independent factor of
decreased phonemic VF at six months. Age was the only independent predictive
factor for incident Parkinson's disease dementia (PDD) (F (4,19)=3.4, P<0.03).
CONCLUSION: An acute post-operative decline in phonemic VF can be predictive of a
long-term phonemic VF deficit. The severity of this cognitive lesion effect does
not predict the development of dementia which appears to be disease-related.
PMID- 25125048
TI - Meta-analysis of the association between two neprilysin gene polymorphisms and
Alzheimer's disease.
AB - OBJECTIVE: The aim of this study is to evaluate the association between two
neprilysin variants (rs989692 and rs3736187) and Alzheimer's disease (AD).
METHODS: All eligible studies were searched in PubMed and Embase from inception
to July 2014. Data was extracted by two investigators independently. The complete
overdominant model (CC+TT vs. CT) and co-dominant model (GG vs. AA and GA vs. AA)
were used for rs989692 and rs3736187, respectively. A comparison of allele
frequencies was also conducted. RESULTS: Six studies containing 2555 AD patients
and 1914 controls were included for rs989692 polymorphisms. The pooled odds ratio
(OR) and confidence interval (CI) suggested that rs989692 polymorphisms were not
associated with AD based on the current published studies (C vs. T, OR = 1.01,
95% CI = 0.85-1.19; CC+TT vs. CT, OR = 0.89, 95% CI = 0.78-1.01). Five studies
containing 2438 AD patients and 1452 controls were identified for rs3736187
polymorphisms (G vs. A, OR = 0.77, 95% CI = 0.66-0.91; GG vs. AA, OR = 0.38, 95%
CI = 0.19-0.77; GA vs. AA, OR = 0.81, 95% CI = 0.61-0.99). The result showed that
rs3736187 polymorphisms were likely associated with the decreased risk of AD.
CONCLUSIONS: This meta-analysis indicates that rs3736187 (A/G) polymorphisms may
be a potential beneficial single nucleotide polymorphism (SNP), which are
associated with a decreased risk in AD. Further larger scale studies are
necessary to validate gene-to-gene interactions and to define the association of
neprilysin polymorphisms with AD.
PMID- 25125049
TI - Expression of suppressor of cytokine signaling 3 in cerebrospinal fluid after
subarachnoid hemorrhage.
AB - BACKGROUND: IL-6 is a proinflammatory cytokine reported to play an important role
in the induction of cerebral vasospasm after subarachnoid hemorrhage (SAH).
Suppressor of cytokine signaling 3 (SOCS3) is known to act as an inhibitor of
signal transduction of IL-6. However, there have been no reports on the
expression of SOCS3 in cerebrospinal fluid (CSF) after SAH. FINDINGS: The
concentration of IL-6 was measured serially up until day 10, in CSF of eight
patients with SAH. CSF samples obtained from patients suffering from an
unruptured aneurysm were used as controls. The expression of SOCS3 in CSF was
further examined by immunoprecipitation methods. Concentrations of IL-6 in CSF
increased immediately after the onset of SAH and remained chronically elevated
over control values. SOCS3 was significantly expressed in CSF on days 1 to 3
after SAH. CONCLUSIONS: Our findings suggest that SOCS3 regulates IL-6 signaling
as an antagonist in CSF, immediately following SAH. As the expression of SOCS3
decreases after day 5, IL-6 signals might then be more easily transmitted,
presumably resulting in cerebral vasospasm.
PMID- 25125051
TI - Apixaban versus enoxaparin in elective major orthopedic surgery: a clinical
review.
AB - Despite current guidelines recommendations about anticoagulant prophylaxis, many
studies have shown an high venous thromboembolism (VTE) incidence in patients
undergoing total hip and knee arthroplasty. A number of anticoagulants are
currently available, but they have some limitations that affect their
applicability and consequently their effectiveness. Several new oral
anticoagulants (NOACs) have been developed in an attempt to overcome these
limitations. Apixaban is a NOAC that selectively inhibits the coagulation factor
Xa; it is approved for the prevention of VTE after total hip replacement and
total knee replacement surgery. This review examines the results of main trials
designed to test efficacy and safety of apixaban in major elective orthopedic
surgery.
PMID- 25125050
TI - Amyloid-beta(1-42) protofibrils stimulate a quantum of secreted IL-1beta despite
significant intracellular IL-1beta accumulation in microglia.
AB - Neuroinflammation is a characteristic feature of the Alzheimer's disease (AD)
brain. Significant inflammatory markers such as activated microglia and cytokines
can be found surrounding the extracellular senile plaques predominantly composed
of amyloid-beta protein (Abeta). Several innate immune pathways, including Toll
like receptors (TLRs) and the NLRP3 inflammasome, have been implicated in AD
inflammation. Abeta plays a primary role in activating these pathways which
likely contributes to the progressive neurodegeneration in AD. In order to better
understand the complexities of this interaction we investigated the inflammatory
response of primary microglia to Abeta(1-42) protofibrils. Abeta(1-42)
protofibrils triggered a time- and MyD88-dependent process that produced tumor
necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) mRNA, and
intracellular pro and mature forms of IL-1beta protein. The accumulation of both
IL-1beta forms indicated that Abeta(1-42) protofibrils were able to prime and
activate the NLRP3 inflammasome. Surprisingly, Abeta-induced accumulation of
intracellular mature IL-1beta did not translate into greater IL-1beta secretion.
Instead, we found that Abeta elicited a quantized burst of secreted IL-1beta and
this process occurred even prior to Abeta priming of the microglia suggesting a
basal level of either pro or mature IL-1beta in the cultured primary microglia.
The IL-1beta secretion burst was rapid but not sustained, yet could be re-evoked
with additional Abeta stimulation. The findings from this study demonstrated
multiple sites of IL-1beta regulation by Abeta(1-42) protofibrils including
TLR/MyD88-mediated priming, NLRP3 inflammasome activation, and modulation of the
IL-1beta secretory process. These results underscore the wide-ranging effects of
Abeta on the innate immune response.
PMID- 25125052
TI - [Magnesium, diabetes and metabolic syndrome].
PMID- 25125053
TI - [Reduction of omalgia in laparoscopic cholecystectomy: clinical randomized trial
ketorolac vs ketorolac and acetazolamide].
AB - BACKGROUND: Laparoscopy cholecystectomy for the surgical treatment of
cholelithiasis has been considered the gold standard. The referred pain to the
shoulder (omalgia) may be present to 63% of the patients and limits outpatient
management. OBJECTIVE: The study was to evaluate the usefulness of acetazolamide
associated with ketorolac for reduction of the omalgia to minimally invasive
treatment. METHODS: We performed a clinical trial, randomized, double blind in
patients undergoing laparoscopic cholecystectomy to assess the reduction of post
operative omalgia comparing ketorolac and ketorolaco+acetazolamida. 31 patients
in each group were studied. The study group: 250 mg of acetazolamide before
anesthetic induction and 30 mg of ketorolac in the immediate postoperative
period. CONTROL GROUP: one tablet of placebo prior to the anesthetic induction
and 30 mg of ketorolac in the immediate postoperative. The presence of omalgia
was assessed using the analog visual scale. The variables recorded included: age,
sex, flow of carbon dioxide intra-abdominal pressure, surgical time, urgent or
elective surgery, omalgia, severity of pain evaluated by analog visual scale,
addition analgesia. RESULTS: Both groups were homogeneous and statistical
analysis showed no differences in the variables studied. The omalgia in the study
group was presented at 9.67% and in the group control was the 58.06% (p < 0.001).
CONCLUSION: 250 mg oral acetazolamide associated 30 mg of ketorolac reduces
significantly the development of omalgia in patients undergoing laparoscopic
cholecystectomy.
PMID- 25125054
TI - [Bile duct lesions repaired with peritoneal tube grafts].
AB - BACKGROUND: A significant number of people suffer iatrogenic bile duct injury
during laparoscopic cholescystectomy. Biliary-digestive bypass may be complicated
by stenosis and biliary sepsis, affecting both quality of life and life
expectancy. To avoid bypass synthetic grafts have been used, which are expensive.
OBJECTIVE: Evaluating autologous implantation of peritoneus as alternative of
bile duct repair. METHODS: Under general anesthesia, ten New Zealand adult
rabbits were operated, common bile duct approached and sectioned underneath the
cystic duct followed by a liver biopsy. An autologous graft was built of
peritoneum and graft-bile duct proximal and distal end-to-end anastomosis done.
Animals were followed-up by weekly bilirrubin and transferases. Rabbits were
scheduled euthanized and a liver biopsy done for histological examinations.
RESULTS: Autologous graft was easy to create and all rabbits survived. They did
not develop jaundice or alterations in their normal habits. At necropsy,
autologous grafts were removed and no signs of occlusion were noticed. Moderate
short-term liver damage was observed but long-term damage was negligible. Bileoma
and pyogenic liver abscess were observed in two animals, respectively.
DISCUSSION: Our results favourably match well-known procedures used for bile duct
repair, especially in cases of severe injury (Bismuth-Strasberg E1-3): it seems
less complicated than biliary-digestive bypass, not as expensive as synthetic
grafts, and much easier to build than human amnion graft. CONCLUSION: Interposing
an autologous graft of peritoneum is an easy-to-create surgical procedure and
circumferential bile duct injuries were adequately repaired.
PMID- 25125055
TI - [Analgesic efficacy of the incisional infiltration of ropivacaine vs ropivacaine
with dexamethasone in the elective laparoscopic cholecystectomy].
AB - BACKGROUND: Incisional pain is the main obstacle for elective laparoscopic
cholecystectomy as an outpatient. We evaluated the analgesic efficacy of local
infiltration of ropivacaine with dexamethasone (Rop/Dx), compared with
ropivacaine (Rop) alone, during the first 24 hours postoperative of this surgery.
Our hypothesis is that incisional pain intensity will be lower in patients of the
group Rop/Dx. METHODS: In a randomized, controlled, double-blind trial clinical,
80 patients were divided into two groups. Group Rop (n= 40) received pre and post
incisional infiltration with 150 mg of ropivacaine in 8 mL of 0.9% saline, while
group Rop/Dx (n= 40) received 150 mg of ropivacaine with 8 mg of dexamethasone in
6 mL of 0.9% saline. The intensity of pain at rest and movement was assessed at
2, 4, 8, 12 and 24 hours postoperatively by a numerical rating scale of 11
points. RESULTS: Incisional pain scores in group Rop/Dx were significantly lower,
compared to the group Rop, at 12 hours (p= 0.05) and 24 hours (p= 0.01) at rest
and at 12 hours (p= 0.04) and 24 hours (p= 0.01) during movement postoperatively.
CONCLUSIONS: We found initial evidence that ropivacaine with dexamethasone for
local infiltration decreased incisional pain intensity after 12 hours post
elective laparoscopic cholecystectomy with a good safety profile.
PMID- 25125056
TI - [Risk factors and evolution of enterocutaneous fistula after terminal ostomy
takedown].
AB - BACKGROUND: End-ileostomy or colostomies are constructed for source control in
patients with severe abdominal sepsis. After takedown, enterocutaneous fistula
represents one of the most feared complications. METHODS: A prospective base was
created with all patients that underwent, during a 90 month period, end-ileostomy
or colostomy takedown after abdominal sepsis. Pre-, intra- and postoperative data
were obtained to identify the factors related to enterocutaneous fistula.
RESULTS: There were 293 patients. Thirty patients (10%) developed enterocutaneous
fistulas. In twenty-four patients the site was at the anastomosis. Identified
risk factors related to enterocutaneous fistula were ASA score III or higher (p<
0.01), ostomy takedown >365 days after its creation (p< 0.05), reoperation (p<
0.001) and anastomotic dehiscence (p< 0.001). Of these patients, twenty (67%) had
spontaneous closure of the fistula, and three more (10%) had surgical closure,
and three patients (10%) died. CONCLUSIONS: Ten percent of patients develop
enterocutaneous fistula after end-ileostomy or colostomy takedown. Patient
selection and delaying time of surgery to obtain complete recovery of the patient
are the most important factors to avoid this complication. Prognosis is related
to the characteristics of the fistula (output and site) and medical treatment.
PMID- 25125057
TI - [Financial expenses incurred by herniated disk in health professionals].
AB - BACKGROUND: Long-term sick leave by illeness is cause of financial expences and
worker's loss of productivity. OBJECTIVE: To evaluate the financial expense
incurred by spinal disk herniation in health professionals. METHODS: 3000 health
professionals of the Instituto Mexicano del Seguro Social work in Tecate, Tijuana
and Rosarito, cities of Baja California, Mexico. During 2009-2011, 1070 health
professionals had long sick leave certificates and 48 had a cervical or lumbar
disk herniation. We evaluated the total days of absenteeism in comparison with
the absenteeism days suggested by the Medical Disability Advisor. RESULTS: Of the
48 spinal herniated disks, 54% were cervical and 65% had surgical management. The
mean (+/- SD) days of absence was 125 +/- 84 and 24 (50%) of the spinal herniated
disks exceeded the Medical Disability Advisor disability duration parameters, in
6 (26%), 12 (52%), and 5 (22%) patients due to no diagnostic concordance,
diagnosis delay and residual pain, respectively. The total cost of the spinal
herniated disks that extended outside of the Medical Disability Advisor
disability duration parameters was 683,026 pesos versus 367,081 pesos of the
spinal herniated disks that did not exceed the Medical Disability Advisor
disability duration parameters. After 12 months of follow-up, 9 (18.8%) continue
with sick leave and 2 (4%) had permanent disability. CONCLUSIONS: In patients
with a spinal herniated disk, the costs of subsidies were two-fold more due
principally to a not diagnostic agreement.
PMID- 25125058
TI - [Temporary disability in operated spine patients. Preliminary report].
AB - BACKGROUND: The spinal injuries in workers have become a large scale health
problem. The purpose of this study is to review the differences in the spine
pathologies from incapacity to work, as well as factors that could alter the
recovery time and the possibility of returning the patient to work. METHODS:
Statistical preliminary review study in 37 patients enrolled in the Instituto
Mexicano del Seguro Social, workers, undertaken to spinal pathology surgery,
comparing days of incapacity with proposed internationally, as well as his return
to work. RESULTS: The results show that 37% of the patients studied are still
active in the social security, 2 years after surgery. The days of disability
generated by the pathology in this study group (212.3 days) are significantly
higher than what is set on the Medical Disability Advisor (56 days, almost 4
times more). CONCLUSION: The study shows the need to develop the same analysis in
other hospitals, comparing the proportion of cases that return to the work and
total disability times for diagnostics.
PMID- 25125059
TI - [New technologies in minimally invasive surgery training: what do surgeons
demand?].
AB - BACKGROUND: Minimally invasive surgery might greatly benefit from the Information
and Communications Technologies. The objective of this work is to determine the
better approach to include those technologies, in particular an e-Learning
platform, into an in-person training course. METHODS: An online survey was sent
to all participants in any of the laparoscopic training courses at Jesus Uson
Minimally Invasive Surgery Centre. This survey included questions regarding new
technologies used for training. Once all data were gathered, a descriptive
analysis was performed. RESULTS: 382 questionnaires were sent of which 102 were
correctly received back. This means a response rate equal to 30%. Current
theoretical training means are watching surgical videos (85-83.3%) and assisting
to in-person training courses (77-75.5%). Participants rated as useful the use of
new technologies for training (4.1 +/- 0.9) and they would mainly use it both
before and after assisting to an in-person training course (80-78.4%).
CONCLUSIONS: It is proposed a methodology that provides participants with
didactic resources based on surgical videos, both before and after assisting to
an in-person training course. Through the application of this methodology, an
improvement and reduction of the time that surgeons expend in training is aimed.
PMID- 25125060
TI - [Pyramid training model in laparoscopic surgery].
AB - BACKGROUND: Minimally invasive surgery implementation requires a regulated and
orderly learning process. METHODS: Jesus Uson Minimally Invasive Surgery Centre
promotes a pyramid training model structured into four levels: training of basic
and advanced skills in physical simulator (level 1), training of anatomical
protocols and advanced skills with animal models (level 2) training advanced
procedural skills with tele-surgical applications (level 3), and training in the
operating room (level 4). Training provided at levels 1 and 2 is described and
evaluated. RESULTS: 4284 participants have been trained in laparoscopy at our
institution. 95.5% surgeons: 49% gastroenterologists, 30% urologists, and 14%
gynecologist (14%). 77% of celebrated courses consisted of 20 hours training (8
at level 1 and 12 at level 2). 94.37% of participants considered pyramid model as
highly suitable, scoring 9.5 on a scale 1-10 for the model and for the simulation
quality. 82.7% perceived the improvement in their laparoscopic skills and 99.56%
recommend this training program to other surgeons. DISCUSSION: There are no
unified criteria between different training programs but most of them measure
laparoscopic skills based on time of execution, quality or mistakes of the
exercise, and the student satisfaction test. CONCLUSION: The pyramid training
model lead to the acquisition of necessary laparoscopic skills to perform safely
advanced minimally invasive techniques.
PMID- 25125061
TI - [Intracranial tumor behavior of plasma cell neoplasms. Report of 2 cases and
literature review].
AB - BACKGROUND: Multiple myeloma is a plasmatic cell neoplasm that is characterized
by skeletal destruction, renal failure, anemia and hypercalcemia. The skull
plasmacytomas represent less than 1% of the head and neck tumors, they can be the
primary lesion or occur as a secondary manifestation of multiple myeloma in 20
30% of the patients, or they can even manifest several years later after the
diagnosis of plasmacytoma. Although some of the lesions may be surgically
accessible, the aggressive natural behavior will complicate the evolution of the
patients. We present two cases of Mexican women with intracranial plasmacytomas,
one of them associated with multiple myeloma. CLINICAL CASES: The first case was
a 24 year-old woman diagnosed with a multiple myeloma with plasmacytic
plasmablastic bone infiltration that was removed in 90%. She presented a local
recurrence that required a second intervention for removal. The second case was a
62 year-old female with a malignant intracranial tumor of plasma cells that was
totally resected. Both patients received adjuvant treatment based on chemotherapy
and radiation therapy with favorable results. The patients died at 5 and 1.5
years respectively due to renal failure secondary to systemic disease.
CONCLUSIONS: We propose chemotherapy and radiation therapy as an essential part
of treatment for this condition, as the aggressive behavior of the neoplasms can
complicate the evolution, despite being surgically accessible.
PMID- 25125062
TI - [Adnexal neoplasms in the context of skin cancer: trichilemmal carcinoma. Apropos
of a case].
AB - BACKGROUND: The trichilemmal carcinoma is a rare malignant neoplasm, whose origin
lies in the annexes of the skin, because of its low prevalence often confused
with other dermal tumors, the differential diagnosis is not easy and is usually
made by exclusion; in theory, its behavior is slow with little tendency to send
both regional lymph node metastasis and systemic. Due to the limited number of
cases there is no consensus on the prognosis, although it is generally considered
good. The aim of this report is to show a case that, contrary to previous
reports, the clinical presentation is aggressive with large soft tissue tumor
infiltration around the site of origin in a patient without risk factors for skin
cancer. CLINICAL CASE: Male patient, 65 years old with cytologic diagnosis of
carcinoma in a preprarotideal facial tumor, characteristics at diagnosis were
infiltration of the facial skin, ear, and parotid gland. Complete block resection
was performed, radical parotiroidectomy and radical neck dissection; the soft
tissue defect was covered with a pediculated flap. The evolution was satisfactory
it follow-up short though. We evaluated the experience in the literature
regarding the prognosis and treatment of these patients. CONCLUSION: Trichilemmal
carcinoma can be fully invasive behavior prognosis is difficult to know and
probably depends on the clinical stage at diagnosis.
PMID- 25125063
TI - [Acute pancreatitis and afferent loop syndrome. Case report].
AB - BACKGROUND: The afferent syndrome loop is a mechanic obstruction of the afferent
limb before a Billroth II or Roux-Y reconstruction, secondary in most of case to
distal or subtotal gastrectomy. Clinical case: Male 76 years old, with antecedent
of cholecystectomy, gastric adenocarcinoma six years ago, with subtotal
gastrectomy and Roux-Y reconstruction. Beginning a several abdominal pain, nausea
and vomiting, abdominal distension, without peritoneal irritation sings. Amylase
1246 U/L, lipase 3381 U/L. Computed Tomography with thickness wall and dilatation
of afferent loop, pancreas with diffuse enlargement diagnostic of acute
pancreatitis secondary an afferent loop syndrome. CONCLUSION: The afferent loop
syndrome is presented in 0.3%-1% in all cases with Billroth II reconstruction,
with a mortality of up to 57%, the obstruction lead accumulation of bile,
pancreatic and intestinal secretions, increasing the pressure and resulting in
afferent limb, bile conduct and Wirsung conduct dilatation, triggering an
inflammatory response that culminates in pancreatic inflammation. The severity of
the presentation is related to the degree and duration of the blockage.
PMID- 25125064
TI - [Sigmoid diverticulitis in adolescent. Case report].
AB - BACKGROUND: Few cases have been reported in children and adolescents of sigmoid
diverticulitis. Most of the case reports in medical literature are associated
with true congenital diverticula and genetic diseases of collagen synthesis.
CLINICAL CASE: 13 year-old female who was admitted to General and Endoscopic
Surgery service with diagnosis of complicated appendicitis. Laparotomy was
performed finding complicated sigmoid diverticular disease. Lavage, sigmoidectomy
and primary anastomosis were performed. The histopathological findings reported a
perforated pseudo-diverticulum of the sigmoid colon with peritonitis. The patient
was discharged 72 hours after surgery and no complications were reported.
CONCLUSION: There are only case reports about colonic diverticulitis in children
and adolescents, and its etiology has not yet been well established. This patient
had sigmoid pseudo-diverticula and did not present genetic concomitant disease.
This case is an exception to data reported on literature about diverticular
disease in this population.
PMID- 25125065
TI - [Experience in kidney transplantation without blood transfusion: kidney
transplantation transfusion-free in Jehovah's Witnesses. First communication in
Mexico].
AB - BACKGROUND: Jehovah's Witness refuse blood transfusion, but they accept organ
transplantation, albumin, immunoglobulin, vaccines and clotting factors. CLINICAL
CASES: We present 3 kidney transplants in Jehovah's Witness patients (two male
and one female) without blood transfusion, with a mean age of 31.33 years and a
mean body mass index of 20.99 kg/m(2). All patients underwent pretransplant
peritoneal dialysis for an average of 52.3 months. Two transplants came from
living donors and one from a deceased donor with a cold ischemia of 23 hours. The
donors were two females and one male, with a mean age of 34.33 years. All
patients received pretransplant erythropoietin and iron dextran and an
intraoperative cell saver was used. Hemoglobin, hematocrit, red blood cells and
serum creatinine levels, as well as the glomerular filtration at 24 months
postransplant were stable. All patients received induction with basiliximab and
initial immunosuppression with calcineurin inhibitors. One of the patients had a
perirenal hematoma as a complication, which required a surgery 20 days post
transplant. At 5, 26 and 36 months postransplant the three patients are alive and
with functional grafts. CONCLUSION: It is possible to perform kidney
transplantation without transfusion in Jehovah's Witness, obtaining an acceptable
global survival without acute rejection.
PMID- 25125066
TI - [Vascular injury as a complication of knee arthroscopic surgery. Report of two
cases and review of the literature].
AB - BACKGROUND: Arthroscopy of the knee is a surgical performed world-wide considered
extremely safe, rates of complication ranging from 0.56 to 8.2%. Vascular
complications are even more rare (0.0032%), and generally related to the
popliteal artery injury. CLINICAL CASE: We are reporting the cases of two
patients who had unsuspected vascular complications after arthroscopy. Both cases
presented vascular injuries after elective knee arthroscopy. First case was a
patient with thrombosed pseudoaneurysm in the popliteal artery and total section
of the popliteal vein, unfortunately the diagnosis was done 72 hrs after knee
arthroscopy and finally required amputation, the 2nd case presented popliteal
arteriovenous fistula, the diagnosis was done 3 weeks after knee arthroscopy, the
patient was successfully treated by resection of the fistula and direct repair of
the artery and vein. CONCLUSIONS: Although extremely infrequent, the vascular
injury after knee arthroscopy should be remembered as a surgical complication, a
low index of suspicion may have caused an unfortunate and untimely delay in
diagnosis and treatment with potential risk of leg amputation and death.
PMID- 25125067
TI - [Caloric restriction: about its positive metabolic effects and cellular impact].
AB - Caloric restriction, as a 30 to 60% decrease of ad libitum balanced caloric
intake, without malnutrition, is the non-genetic strategy that has consistently
extended the average and maximum lifespan of most living beings, and it has been
tested from unicellular organisms like yeast Saccharomyces cerevisiae to Rhesus
primates. In addition, various genetic and pharmacological caloric restriction
models have shown to protect against cancer, cardiovascular and neurodegenerative
diseases. Primate studies suggest that this intervention delays the onset of age
related diseases; in humans, it has physiological, biochemical and metabolic
effects decreasing diabetes and cardiovascular disease risk factor. Although
currently the mechanism by which caloric restriction has its positive effects at
the cellular level is unknown, it has been reported to decrease oxidative stress
and increase in mitochondrial biogenesis.
PMID- 25125069
TI - Follicular lymphoma of the ocular adnexal region: a nation-based study.
AB - PURPOSE: To characterize the clinicopathological features of follicular lymphoma
of the ocular adnexal region. METHODS: Retrospective nation-based study of Danish
patients with ocular adnexal follicular lymphoma from January 1st 1980 through
December 31st 2009. RESULTS: Twenty-four patients with ocular adnexal follicular
lymphoma were identified. Fourteen (58%) of the patients were females. The median
age was 63 years (range: 42-96 years). Eleven (46%) of the patients had primary
ocular adnexal lymphoma, seven (29%) had an ocular adnexal lesion in conjunction
with a concurrent systemic lymphoma and six patients (25%) presented with an
ocular adnexal relapse. The most frequently affected sites were the lacrimal
gland (38%) and the orbit (33%). Thirteen patients (54%) presented with Ann Arbor
stage IE lymphoma, four (17%) had stage IIE, two patients (8%) stage IIIE, and
five patients (21%) had stage IV lymphoma. Radiotherapy was primarily used in
patients with primary lymphoma and those with a stage IE/IIE relapse (82%), while
stage IIIE/IV lymphomas most frequently received alkylating chemotherapy (67%).
Complete remission was observed in 19 of the patients (79%), but of these 11(58%)
had a relapse. The 10-year overall survival for the entire cohort was 59%. The
translocation t(14;18) was detected in 16 patients (16/24, 76%). Recurrence was
only observed in patients with the t(14;18) (p=0.05, log-rank). CONCLUSIONS:
Ocular adnexal follicular lymphoma is more commonly found in elderly female
patients. The lacrimal gland is relatively frequently involved. Radiotherapy is
the treatment of choice for localized ocular adnexal follicular lymphoma
providing a favourable prognosis for majority of patients.
PMID- 25125068
TI - Internet-mediated physiotherapy and pain coping skills training for people with
persistent knee pain (IMPACT - knee pain): a randomised controlled trial
protocol.
AB - BACKGROUND: Persistent knee pain in people over 50 years of age is often
attributable to knee osteoarthritis (OA), a common joint condition that causes
physical and psychological dysfunction. Exercise and pain coping skills training
(PCST) can help reduce the impact of persistent knee pain, however, access to
health professionals who deliver these services can be challenging. With
increasing access to the Internet, remotely delivered Internet-based treatment
approaches may provide alternatives for healthcare delivery. This pragmatic
randomised controlled trial will investigate whether an Internet-delivered
intervention that combines PCST and physiotherapist-guided exercise (PCST + Ex)
is more effective than online educational material (educational control) in
people with persistent knee pain. METHODS/DESIGN: We will recruit 148 people over
50 years of age with self-reported persistent knee pain consistent with knee OA
from the Australian community. Following completion of baseline questionnaires,
participants will be randomly allocated to access a 3-month intervention of
either (i) online educational material, or (ii) the same online material plus an
8-module (once per week) Internet-based PCST program and seven Internet-delivered
physiotherapy sessions with a home exercise programs to be performed 3 times per
week. Outcomes will be measured at baseline, 3 months and 9 months with the
primary time point at 3 months. Primary outcomes are average knee pain on walking
(11-point numeric rating scale) and self-reported physical function (Western
Ontario and McMaster Universities Osteoarthritis Index subscale). Secondary
outcomes include additional measures of knee pain, health-related quality-of
life, perceived global change in symptoms, and potential moderators and mediators
of outcomes including self-efficacy for pain management and function, pain coping
attempts and pain catastrophising. Other measures of adherence, adverse events,
harms, use of health services/co-interventions, and process measures including
appropriateness and satisfaction of the intervention, will be collected at 3, 6
and 9 months. DISCUSSION: The findings will help determine the effectiveness and
acceptability of Internet access to a combination of interventions that are known
to be beneficial to people with persistent knee pain. This study has the
potential to guide clinical practice towards innovative modes of healthcare
provision. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
reference: ACTRN12614000243617.
PMID- 25125071
TI - Posterior sclera reinforcement and phakic intraocular lens implantation for
highly myopic amblyopia in children: a 3-year follow-up.
AB - PURPOSE: To study the safety and efficacy of posterior scleral reinforcement
(PSR) combined with phakic intraocular lens (PIOLs) implantation for highly
myopic amblyopia in children. METHODS: This study included eight highly myopic
children (11 eyes) who failed in conventional therapy for amblyopia using various
combination of spectacles, contact lenses, and intensive patching before
enrollment into this study. They were treated sequentially with PSR and PIOL
implantation, and were followed up for 3 years after surgery. Uncorrected visual
acuity (UCVA) and best corrected visual acuity (BCVA) in LogMAR, spherical
equivalent power (SE), and complications were evaluated. RESULTS: Before surgery,
the mean UCVA was 1.59+/-0.33, BCVA, 0.74+/-0.37, SE, -17.57+/-5.56D, the axial
length (AL), 30.09+/-2.18 mm. After PSR, BCVA improved one line in three
patients, the rest were unchanged, and AL was unchanged among all cases. Six eyes
of three patients were implanted with an iris-claw PIOL and five eyes of five
patients were implanted with a posterior PIOL. After completion of treatment, the
mean UCVA was 0.44+/-0.21, BCVA 0.38+/-0.24, SE -0.54+/-0.74 D, and AL 30.35+/
2.29 mm. No patient experienced complications. CONCLUSION: Combined PSR and PIOL
implantation treatment for highly myopic amblyopia in children is safe and
effective.
PMID- 25125070
TI - Prevalence of glaucoma in patients with moderate to severe obstructive sleep
apnea: ocular morbidity and outcomes in a 3 year follow-up study.
AB - PURPOSE: This study was conducted to investigate the prevalence and progression
of glaucoma in patients receiving treatment for obstructive sleep apnea (OSA). We
also investigated whether there is an association between severity of OSA and the
incidence of glaucoma. METHODS: A total of 39 patients aged >30 years who had
been diagnosed with moderate and severe OSA in the sleep clinic at Hamad General
Hospital were assessed for the presence of glaucoma. The severity of OSA was
graded as mild, moderate, or severe based on American Association of Sleep
Medicine (AASM) criteria using the apnea hypopnea index. Before enrollment, all
patients underwent a complete ophthalmic examination including serial visual
field tests, optical coherence tomography (OCT) with fundus photographs, and
pachymetry. Enrolled patients were followed up in the ophthalmology outpatient
clinic and sleep clinic for a period of 3 years. RESULTS: Examinations found that
8 (20.5%; 95% confidence interval (CI) 9.9-37%) of the 39 patients with OSA had
glaucoma. Six (75%; 95% CI 36-96%) of these patients had normal-tension glaucoma
(NTG) and two (25%; 95% CI 4.5-64.4%) patients had high-tension glaucoma. Among
the 27 patients with severe OSA, 7 (25.9%; 95% CI 8-34%) had glaucoma, and among
12 patients with moderate OSA, 1 (8.3%; 95% CI 0.1-15%) had glaucoma. During the
course of follow-up, two patients who previously did not have glaucoma were
reclassified as NTG and two patients with glaucoma deteriorated. A higher
prevalence of glaucoma in the severe OSA group compared with the moderate OSA
group was found, albeit a statistically significant difference could not be
attained (P=0.4). CONCLUSIONS: Our study showed that severe OSA is an important
risk factor for developing glaucoma. Adequate treatment of OSA, along with
optimal ophthalmic care, resulted in better control of glaucoma.
PMID- 25125073
TI - Combinatorial gene therapy accelerates bone regeneration: non-viral dual delivery
of VEGF and BMP2 in a collagen-nanohydroxyapatite scaffold.
AB - Vascularization and bone repair are accelerated by a series of gene-activated
scaffolds delivering both an angiogenic and an osteogenic gene. Stem cell
mediated osteogenesis in vitro, in addition to increased vascularization and bone
repair by host cells in vivo, is enhanced using all systems while the use of the
nanohydroxyapatite vector to deliver both genes markedly enhances bone healing.
PMID- 25125074
TI - Johann Vesling (1598-1649): seventeenth century anatomist of Padua and his
Syntagma Anatomicum.
AB - Johann Vesling (1598-1649) was a German anatomist and surgeon who belonged to the
golden period of the illustrious University of Padua. He made significant
contributions to the advancement of anatomical knowledge during the 17th century
and is remembered most for his remarkable anatomical work, the Syntagma
Anatomicum, which was published in 1641. He was the first to describe the soleus
muscle and to emphasize its resemblance to the sole fish. He produced the
earliest illustrations of the human lymphatic system and was one of the first to
document observations about the thoracic duct. He was also the first to report
the bifurcation of the human hepatic portal vein on entering the fissure of the
liver. His observations from embryological experiments were critical for
understanding the development of the four-chambered heart. He was one of the
first authors to state that four pulmonary veins empty into the left atrium of
the heart. Syntagma Anatomicum (1641) was the most widely used anatomical text in
Europe for almost a century and was republished a number of times with editions
in Latin, German, Dutch, and English. Syntagma was the first illustrated western
anatomical text to reach Japan and laid the foundation for the development of
European medicine there. The illustrations used in it deviated from the artistic
convention that had characterized anatomical figures from the time of Vesalius,
and focused instead on representing anatomical details to make them helpful for
medicine and surgery. Clin. Anat. 27:1122-1127, 2014. (c) 2014 Wiley Periodicals,
Inc.
PMID- 25125072
TI - Optical quality of the diabetic eye: a review.
AB - Diabetes mellitus is a metabolic disorder characterized by the presence of
chronic hyperglycaemia. Several structural, morphological, and physiological
changes in each of ocular component have been described in detail during the past
decades. Due to these abnormalities, the diabetic patient undergoes a degradation
of the retinal image by an increase of higher ocular aberrations and ocular
scattering coming from mainly tear film, cornea, and crystalline lens. This
review aims to provide an overview of current knowledge about the effects of
diabetes mellitus in these optical phenomena and its consequence on the visual
quality of the diabetic patient.
PMID- 25125075
TI - Prevalence of and risk factors for diabetic macular edema in the United States.
AB - IMPORTANCE: Diabetic macular edema (DME) is a leading cause of vision loss in
persons with diabetes mellitus. Although there are national estimates for the
prevalence of diabetic retinopathy and its risk factors among persons with
diabetes, to our knowledge, no comparable estimates are available for DME
specifically. OBJECTIVES: To estimate the prevalence of DME in the US population
and to identify associated risk factors. DESIGN, SETTING, AND PARTICIPANTS: A
cross-sectional analysis of 1038 participants aged 40 years or older with
diabetes and valid fundus photographs in the 2005 to 2008 National Health and
Nutrition Examination Survey. MAIN OUTCOMES AND MEASURES: The overall prevalence
of DME and its prevalence according to age, race/ethnicity, and sex. RESULTS: Of
the 1038 persons with diabetes analyzed for this study, 55 had DME, for an
overall weighted prevalence of 3.8% (95% CI, 2.7%-4.9%) or approximately 746, 000
persons in the US 2010 population aged 40 years or older. We identified no
differences in the prevalence of DME by age or sex. Multivariable logistic
regression analysis showed that the odds of having DME were higher for non
Hispanic blacks than for non-Hispanic whites (odds ratio [OR], 2.64; 95% CI, 1.19
5.84; P = .02). Elevated levels of glycosylated hemoglobin A1c (OR, 1.47; 95% CI,
1.26-1.71 for each 1%; P < .001) and longer duration of diabetes (OR, 8.51; 95%
CI, 3.70-19.54 for >= 10 vs <10 years; P < .001) were also associated with DME
prevalence. CONCLUSIONS AND RELEVANCE: These results suggest a greater burden of
DME among non-Hispanic blacks, individuals with high levels of hemoglobin A1c,
and those with longer duration of diabetes. Given recent treatment advances in
reducing vision loss and preserving vision in persons with DME, it is imperative
that all persons with diabetes receive early screening; this recommendation is
even more important for those at higher risk for DME.
PMID- 25125076
TI - Use of three-dimensional time-resolved phase-contrast magnetic resonance imaging
with vastly undersampled isotropic projection reconstruction to assess renal
blood flow in a renal cell carcinoma patient treated with sunitinib: a case
report.
AB - BACKGROUND: New imaging modalities to assess the efficacy of drugs that have
molecular targets remain under development. Here, we describe for the first time
the use of time-resolved three-dimensional phase-contrast magnetic resonance
imaging to monitor changes in blood supply to a tumor during sunitinib treatment
in a patient with localized renal cell carcinoma. CASE PRESENTATION: A 43-year
old Japanese woman with a tumor-bearing but functional single kidney presented at
our hospital in July 2012. Computed tomography and magnetic resonance imaging
revealed a cT1aN0M0 renal cell carcinoma embedded in the upper central region of
the left kidney. She was prescribed sunitinib as neoadjuvant therapy for 8
months, and then underwent partial nephrectomy. Tumor monitoring during this time
was done using time-resolved three-dimensional phase-contrast magnetic resonance
imaging, a recent technique which specifically measures blood flow in the various
vessels of the kidney. This imaging allowed visualization of the redistribution
of renal blood flow during treatment, and showed that flow to the tumor was
decreased and flows to other areas increased. Of note, this change occurred in
the absence of any change in tumor size. CONCLUSION: The ability of time-resolved
three-dimensional phase-contrast magnetic resonance imaging to provide
quantitative information on blood supply to tumors may be useful in monitoring
the efficacy of sunitinib treatment.
PMID- 25125077
TI - Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD
after up to 33 years of follow-up.
AB - Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the
Western world, strongly associated with insulin resistance and the metabolic
syndrome. Nonalcoholic steatohepatitis, i.e., fatty liver accompanied by
necroinflammatory changes, is mostly defined by the NAFLD activity score (NAS).
The aim of the current study was to determine disease-specific mortality in
NAFLD, and evaluate the NAS and fibrosis stage as prognostic markers for overall
and disease-specific mortality. In a cohort study, data from 229 well
characterized patients with biopsy-proven NAFLD were collected. Mean follow-up
was 26.4 (+/-5.6, range 6-33) years. A reference population was obtained from the
National Registry of Population, and information on time and cause of death were
obtained from the Registry of Causes of Death. NAFLD patients had an increased
mortality compared with the reference population (hazard ratio [HR] 1.29,
confidence interval [CI] 1.04-1.59, P = 0.020), with increased risk of
cardiovascular disease (HR 1.55, CI 1.11-2.15, P = 0.01), hepatocellular
carcinoma (HR 6.55, CI 2.14-20.03, P = 0.001), infectious disease (HR 2.71, CI
1.02-7.26, P = 0.046), and cirrhosis (HR 3.2, CI 1.05-9.81, P = 0.041). Overall
mortality was not increased in patients with NAS 5-8 and fibrosis stage 0-2 (HR
1.41, CI 0.97-2.06, P = 0.07), whereas patients with fibrosis stage 3-4,
irrespective of NAS, had increased mortality (HR 3.3, CI 2.27-4.76, P < 0.001).
CONCLUSION: NAFLD patients have increased risk of death, with a high risk of
death from cardiovascular disease and liver-related disease. The NAS was not able
to predict overall mortality, whereas fibrosis stage predicted both overall and
disease-specific mortality.
PMID- 25125078
TI - PTEN regulates plasma membrane expression of glucose transporter 1 and glucose
uptake in thyroid cancer cells.
AB - Glucose represents an important source of energy for the cells. Proliferating
cancer cells consume elevated quantity of glucose, which is converted into
lactate regardless of the presence of oxygen. This phenomenon, known as the
Warburg effect, has been proven to be useful for imaging metabolically active
tumours in cancer patients by (18)F-fluorodeoxyglucose positron emission
tomography (FDG-PET). Glucose is internalised in the cells by glucose
transporters (GLUTs) belonging to the GLUT family. GLUT1 (SLC2A1) is the most
prevalent isoform in more aggressive and less differentiated thyroid cancer
histotypes. In a previous work, we found that loss of expression of PTEN was
associated with increased expression of GLUT1 on the plasma membrane (PM) and
probability of detecting thyroid incidentalomas by FDG-PET. Herein, we
investigated the molecular pathways that govern the expression of GLUT1 on the PM
and the glucose uptake in WRO (expressing WT PTEN) and FTC133 (PTEN null)
follicular thyroid cancer cells cultured under glucose-depleted conditions. The
membrane expression of GLUT1 was enhanced in glucose-deprived cells. Through
genetic manipulations of PTEN expression, we could demonstrate that the lack of
this oncosuppressor has a dominant effect on the membrane expression of GLUT1 and
glucose uptake. We conclude that loss of function of PTEN increases the
probability of cancer detection by FDG-PET or other glucose-based imaging
diagnosis.
PMID- 25125080
TI - Recent advances in the discovery of N-myristoyltransferase inhibitors.
AB - N-Myristoyltransferase (NMT) is a cytosolic monomeric enzyme present in
eukaryotes such as fungi and protozoa, but is not found in prokaryotes. The
attachment of a 14-carbon saturated fatty acid, myristate, from myristoyl-CoA
(14:0 CoA) to the N-terminal glycine residue in a specific set of cellular
proteins is commonly called protein N-myristoylation. The myristoylation reaction
catalyzed by the enzyme myristoyl CoA:NMT is both necessary for the growth of
various organisms and conclusive for cellular proliferation. Therefore, NMT has
been identified as a novel and promising target for antifungal, antiparasitic,
and anticancer agents, and a large number of potent NMT inhibitors with
antifungal, antiparasitic, and anticancer activities have been reported. Herein
we describe recent advances in the discovery of NMT inhibitors. We introduce not
only the functions of NMT, but also some representative natural and synthetic
inhibitors, with a focus on their biological activity, selectivity, and structure
activity relationship (SAR) information. In particular, inspiration from NMT
inhibitor structures and the future direction of these compounds are highlighted.
PMID- 25125081
TI - Requests for dermatology specialist consultations show an inverse correlation
with waiting time: an analysis of waiting time to access dermatology specialist
health care in Bolzano, South Tyrol, Italy.
PMID- 25125079
TI - Clopidogrel discontinuation within the first year after coronary drug-eluting
stent implantation: an observational study.
AB - BACKGROUND: The impact of adherence to the recommended duration of dual
antiplatelet therapy after first generation drug-eluting stent implantation is
difficult to assess in real-world settings and limited data are available.
METHODS: We followed 4,154 patients treated with coronary drug-eluting stents in
Western Denmark for 1 year and obtained data on redeemed clopidogrel
prescriptions and major adverse cardiovascular events (MACE, i.e., cardiac death,
myocardial infarction, or stent thrombosis) from medical databases. RESULTS:
Discontinuation of clopidogrel within the first 3 months after stent implantation
was associated with a significantly increased rate of MACE at 1-year follow-up
(hazard ratio (HR) 2.06; 95% confidence interval (CI): 1.08-3.93).
Discontinuation 3-6 months (HR 1.29; 95% CI: 0.70-2.41) and 6-12 months (HR 1.29;
95% CI: 0.54-3.07) after stent implantation were associated with smaller, not
statistically significant, increases in MACE rates. Among patients who
discontinued clopidogrel, MACE rates were highest within the first 2 months after
discontinuation. CONCLUSIONS: Discontinuation of clopidogrel was associated with
an increased rate of MACE among patients treated with drug-eluting stents. The
increase was statistically significant within the first 3 months after drug
eluting stent implantation but not after 3 to 12 months.
PMID- 25125084
TI - Physiological flexibility in an avian range expansion.
AB - The mechanisms that enable animals to colonize new areas are little known, but
growing evidence indicates that the regulation of stress hormones is important.
Stress hormones probably influence invasions because they enable organisms to
adjust their phenotypes depending on environmental context. Often, studies of
stress hormones are based on single or a few samples from individuals even though
the flexibility in the regulation of such hormones is what enables them to
achieve homeostasis and facilitate performance. Here, we asked whether
flexibility in the regulation of one stress hormone, corticosterone, was related
to colonization success in one of the world's most successful avian invaders, the
house sparrow (Passer domesticus). We studied Kenyan house sparrows, as the
species was recently introduced there (around 1950) and has since expanded
northwestward. Previous work in this system revealed that younger populations
released more corticosterone during a restraint stressor than older populations.
Our first goal was to discern whether such population differences were fixed or
flexible in adulthood; our second goal was to determine whether individual
identity explained any variation in corticosterone regulation. As before, we
found that corticosterone responses to short-term restraint (i.e., stress
responses), but not baseline corticosterone, were larger in younger populations.
We also found that both baseline and stress-induced corticosterone measures were
flexible; both metrics became similar among sites after one week of captivity.
For stress responses, we also found that individual identity was important.
Altogether, the present data suggest that the colonization of Kenya by house
sparrows might have been facilitated by stress hormone regulatory flexibility.
PMID- 25125083
TI - Neuroendocrine gene expression reveals a decrease in dopamine D2B receptor with
no changes in GnRH system during prepubertal metamorphosis of silvering in wild
Japanese eel.
AB - Silvering is a prepubertal metamorphosis preparing the eel to the oceanic
reproductive migration. A moderate gonad development occurs during this
metamorphosis from the sedentary yellow stage to the migratory silver stage. The
aim of this study was to elucidate the molecular aspects of various endocrine
parameters of BPG axis at different ovarian developmental stages in wild yellow
and silver female Japanese eels. The GSI of the sampled female eels ranged
between 0.18 and 2.3%, corresponding to yellow, pre-silver and silver stages.
Gonad histology showed changes from previtellogenic oocytes in yellow eels to
early vitellogenic oocytes in silver eels. Both serum E2 and T concentrations
significantly increased with ovarian development indicating a significant
activation of steroidogenesis during silvering. In agreement with previous
studies, significant increases in pituitary gonadotropin beta subunits FSH-beta
and LH-beta transcripts were also measured by qPCR, supporting that the
activation of pituitary gonadotropin expression is likely responsible for the
significant ovarian development observed during silvering. We investigated for
the first time the possible brain neuroendocrine mechanisms involved in the
activation of the pituitary gonadotropic function during silvering. By analyzing
the expression of genes representative of the stimulatory GnRH control and the
inhibitory dopaminergic control. The transcript levels of mGnRH and the three
GnRH receptors did not change in the brain and pituitary between yellow and
silver stages, suggesting that gene expression of the GnRH system is not
significantly activated during silvering. The brain transcript levels of tyrosine
hydroxylase, limiting enzyme of DA synthesis did not change during silvering,
indicating that the DA synthesis activity was maintained. In contrast, a
significant decrease in DA-D2B receptor expression in the forebrain and pituitary
was observed, with no changes in DA-D2A receptor. The decrease in the pituitary
expression of DA-D2BR during silvering would allow a reduced inhibitory effect of
DA. We may raise the hypothesis that this regulation of D2BR gene expression is
one of the neuroendocrine mechanisms involved in the slight activation of the
pituitary gonadotropin and gonadal activity that occur at silvering.
PMID- 25125085
TI - Impact of platelet transfusion on toxicity and mortality after hematopoietic
progenitor cell transplantation.
AB - BACKGROUND: Thrombocytopenia occurs commonly after hematopoietic progenitor cell
transplantation (HPCT) and is associated with potential morbidity and mortality.
Few studies have examined the impact of platelet (PLT) transfusion on clinical
outcomes in HPCT while optimal PLT transfusion strategies after HSCT remain
uncertain. STUDY DESIGN AND METHODS: A retrospective single-center cohort study
was conducted on 522 patients undergoing HPCT between January 2002 and December
2007. Associations between PLT transfusion events and clinical characteristics
with transplant-related outcomes were assessed using univariate and multivariate
analysis. RESULTS: Mean number of PLT transfusion events before Day +60
posttransplant was 7.5 (95% confidence interval, 6.7-8.4) with greater number of
events after allogeneic compared with autologous HPCT (p < 0.01). Univariate and
multivariate analysis confirmed that the number of PLT transfusion events was
associated with increased 100-day nonrelapse mortality (p < 0.01), posttransplant
length of hospital stay (p < 0.01), need for intensive care unit admission (p <
0.01), and number of organs affected by severe toxicity (p < 0.01). CONCLUSION:
HPCT-related toxicity and mortality are associated with increased PLT transfusion
events. Alternative strategies to reduce PLT transfusions after HPCT may warrant
future study.
PMID- 25125082
TI - Metabolic stressors and signals differentially affect energy allocation between
reproduction and immune function.
AB - Most free-living animals have finite energy stores that they must allocate to
different physiological and behavioral processes. In times of energetic stress,
trade-offs in energy allocation among these processes may occur. The
manifestation of trade-offs may depend on the source (e.g., glucose, lipids) and
severity of energy limitation. In this study, we investigated energetic trade
offs between the reproductive and immune systems by experimentally limiting
energy availability to female Siberian hamsters (Phodopus sungorus) with 2-deoxy
d-glucose, a compound that disrupts cellular utilization of glucose. We observed
how glucoprivation at two levels of severity affected allocation to reproduction
and immunity. Additionally, we treated a subset of these hamsters with leptin, an
adipose hormone that provides a direct signal of available fat stores, in order
to determine how increasing this signal of fat stores influences glucoprivation
induced trade-offs. We observed trade-offs between the reproductive and immune
systems and that these trade-offs depended on the severity of energy limitation
and exogenous leptin signaling. The majority of the animals experiencing mild
glucoprivation entered anestrus, whereas leptin treatment restored estrous
cycling in these animals. Surprisingly, virtually all animals experiencing more
severe glucoprivation maintained normal estrous cycling throughout the
experiment; however, exogenous leptin resulted in lower antibody production in
this group. These data suggest that variation in these trade-offs may be mediated
by shifts between glucose and fatty acid utilization. Collectively, the results
of the present study highlight the context-dependent nature of these trade-offs,
as trade-offs induced by the same metabolic stressor can manifest differently
depending on its intensity.
PMID- 25125086
TI - Manganese-mediated intermolecular arylation of H-phosphinates and related
compounds.
AB - The intermolecular radical functionalization of arenes with aryl and alkyl H
phosphinate esters, as well as diphenylphosphine oxide and H-phosphonate
diesters, is described. The novel catalytic Mn(II) /excess Mn(IV) system is a
convenient and inexpensive solution to directly convert Csp2 ?H into C?P bonds.
The reaction can be employed to functionalize P-stereogenic H-phosphinates since
it is stereospecific. With monosubstituted aromatics, the selectivity for para
substitution increases in the order (RO)2 P(O)H=30 LPD)
and smaller (<=29 LPD) series. Pathology demonstrated ductal adenocarcinoma in
30.6 % of the specimens, other malignant tumors in 51.7 %, and benign
tumor/disease in 17.5 %. The mean number of lymph nodes examined was 14.4 (7-32),
and the rate of microscopically positive tumor margin was 4.4 %. CONCLUSIONS: In
selected patients, operated on by expert laparoscopic pancreatic surgeons, LPD is
feasible and safe.
PMID- 25125093
TI - Incidence and risk factors of incisional hernia formation following abdominal
organ transplantation.
AB - BACKGROUND: Hernia formation is common following abdominal operations, and
transplant patients are at increased risk due to postoperative immunosuppression.
The purpose of this study was to estimate the incidence of incisional hernia
formation following primary abdominal solid organ transplantation and identify
clinical risk factors for hernia formation. METHODS: We performed a single
institution retrospective review of a prospectively collected database to
evaluate all patients who underwent primary liver, kidney, or pancreas
transplantation between 2000 and 2011. The primary outcome was hernia formation
at the transplant incision. Univariate and multivariate Cox proportional hazards
models were used to identify risk factors for incisional hernia formation.
RESULTS: A total of 3,460 transplants were performed during the study period:
2,247 kidney only, 718 liver only, and 495 pancreas or simultaneous pancreas and
kidney (pancreas group). The overall incisional hernia rate was 7.5 %. The Kaplan
Meier rates of hernia formation at 1, 5, and 10 years were 2.5, 4.9, and 7.0 %
for kidney; 4.5, 13.6, and 19.0 % for liver; and 2.5, 12.7, and 21.8 % for the
pancreas groups. On univariate analysis, surgical site infection (SSI), body mass
index (BMI) >25, delayed graft function, and withholding a calcineurin inhibitor
or mycophenolate mofetil (MMF) were associated with hernia formation in the
kidney group. SSI and BMI >25 were associated with hernia formation in the liver
group. In the pancreas group, SSI, cyclosporine, and withholding MMF were all
associated with hernia formation. On multivariate analysis, SSI was strongly
associated with hernia formation in all groups. Hazard ratio: kidney = 24.71
(13.00-46.97); liver = 12.0 (6.40-22.52); pancreas = 12.95 (2.78-60.29).
CONCLUSION: Incisional hernias are common following abdominal organ transplant
with nearly one in five patients developing an incisional hernia 5 years after
liver or pancreas transplantation. Strategies focusing on prevention and early
treatment of SSI may help to decrease the risk of incisional hernia formation
following abdominal organ transplantation.
PMID- 25125094
TI - Differences in gaze behaviour of expert and junior surgeons performing open
inguinal hernia repair.
AB - INTRODUCTION: Various fields have used gaze behaviour to evaluate task
proficiency. This may also apply to surgery for the assessment of technical
skill, but has not previously been explored in live surgery. The aim was to
assess differences in gaze behaviour between expert and junior surgeons during
open inguinal hernia repair. METHODS: Gaze behaviour of expert and junior
surgeons (defined by operative experience) performing the operation was recorded
using eye-tracking glasses (SMI Eye Tracking Glasses 2.0, SensoMotoric
Instruments, Germany). Primary endpoints were fixation frequency (steady eye gaze
rate) and dwell time (fixation and saccades duration) and were analysed for
designated areas of interest in the subject's visual field. Secondary endpoints
were maximum pupil size, pupil rate of change (change frequency in pupil size)
and pupil entropy (predictability of pupil change). NASA TLX scale measured
perceived workload. Recorded metrics were compared between groups for the entire
procedure and for comparable procedural segments. RESULTS: Twenty-five cases were
recorded, with 13 operations analysed, from 9 surgeons giving 630 min of data,
recorded at 30 Hz. Experts demonstrated higher fixation frequency (median[IQR]
1.86 [0.3] vs 0.96 [0.3]; P = 0.006) and dwell time on the operative site during
application of mesh (792 [159] vs 469 [109] s; P = 0.028), closure of the
external oblique (1.79 [0.2] vs 1.20 [0.6]; P = 0.003) (625 [154] vs 448 [147] s;
P = 0.032) and dwelled more on the sterile field during cutting of mesh (716
[173] vs 268 [297] s; P = 0.019). NASA TLX scores indicated experts found the
procedure less mentally demanding than juniors (3 [2] vs 12 [5.2]; P = 0.038). No
subjects reported problems with wearing of the device, or obstruction of view.
CONCLUSION: Use of portable eye-tracking technology in open surgery is feasible,
without impinging surgical performance. Differences in gaze behaviour during open
inguinal hernia repair can be seen between expert and junior surgeons and may
have uses for assessment of surgical skill.
PMID- 25125095
TI - A comparative study of survival after minimally invasive and open oesophagectomy.
AB - BACKGROUND: Oesophageal cancer is increasing in incidence worldwide. Minimally
invasive techniques have been used to perform oesophagectomy, but concerns
regarding these techniques remain. Since its description by Cuschieri in 1992,
the use of minimally invasive oesophagectomy (MIO) has increased, but still only
used in a minority of resections in the UK in 2009. In particular, there has been
reluctance to use minimally invasive (thoracoscopic and laparoscopic) techniques
in more advanced cancers for fears regarding the adequacy of the oncological
resection. In order to identify any factors that could affect survival, we
undertook a retrospective analysis on all patients who underwent surgery in our
department over an 8-year period. METHODS: A retrospective data analysis was
undertaken on all patients who underwent oesophagectomy in a tertiary upper
gastrointestinal surgery unit, from 2005 to 2012 inclusive. Data were collected
from the departmental database and case note review, with follow-up and survival
data to time of data collection. The survival data were analysed using univariate
and multivariate Cox proportional hazard regression models to determine which
variables affected survival. Variables examined included age, tumour position,
tumour stage (T0, 1, 2 vs T3, 4), nodal stage (N0 vs N1), tumour histology,
completeness of resection (R0 vs R1), use of neoadjuvant chemotherapy and
operative technique (thoracoscopic/laparoscopic (MIO) vs laparoscopic
abdomen/open chest (Lap assisted) vs Open. RESULTS: 334 patients underwent
oesophagectomy between 2005 and 2012. Male to female ratio was 3.75:1, with a
mean age of 64 years (range 36-87). There were 83 open oesophagectomies, 187
laparoscopically assisted oesophagectomies and 64 minimally invasive
oesophagectomies. Following univariate regression analysis the following factors
were found to be correlated to survival: use of neoadjuvant chemotherapy (Hazard
Ratio 2.889, 95 % CI 1.737-4.806), T stage 3 or 4 (3.749, 2.475-5.72), Node
positive (5.225, 3.561-7.665), R1 resection (2.182, 1.425-3.341), type of
operation (MIO compared to open oesophagectomy) (0.293, 0.158-0.541). There was
no significant relationship between age, tumour position or tumour histology and
length of survival. When these factors were entered into a multivariate model,
the independently significant factors correlated to survival were found to be T
stage 3 or 4 (HR 1.969, 1.248-3.105), Node positive (3.833, 2.548-5.766) and type
of operation (MIO compared to open) (0.5186, 0.277-0.972). CONCLUSION: Multiple
small studies have found reduced pulmonary complication rates and duration of
hospital stay when using a minimally invasive approach compared to open. Concerns
in the literature over long-term outcomes, however, have led to limited
utilisation of this method, especially in advanced disease. The data from this
large study show significantly better survival following operations performed
using minimally invasive techniques compared to open, however, we have not
adjusted for some known or unknown confounding factors. International and
national RCTs, however, will provide more information in due course.
PMID- 25125096
TI - Laparoscopy in the diagnosis and repair of diaphragmatic injuries in left-sided
penetrating thoracoabdominal trauma: laparoscopy in trauma.
AB - BACKGROUND: Diaphragmatic injuries from penetrating thoracoabdominal trauma are
notoriously difficult to detect with clinical and radiological evaluation. The
aim of this study was to establish the incidence of diaphragmatic injury from
penetrating thoracoabdominal trauma, clinical and radiological features
predictive of a diaphragmatic injury and the feasibility of laparoscopic repair.
METHODS: This is a prospective consecutive case series conducted in a
metropolitan hospital complex. Fifty five patients were enrolled into the study
and underwent a standardized laparoscopic procedure. Only stable patients were
selected and right-sided penetrating thoracoabdominal injuries were excluded. The
patients' clinical details, radiological findings, operative procedure, treatment
of the diaphragmatic injury and complications were collected and analysed.
RESULTS: There were a total of 55 patients, of whom, 22 (40 %) had diaphragmatic
injuries. The mean age was 26.3 +/- 7.8 years (range 15-44) with a male:female
ratio of 10:1. The causes of injury were stab in 54 (98.2 %) patients and firearm
in one (1.8 %). Twenty six (47.3 %) patients had positive radiological findings,
of which 10 (38.5 %) had a diaphragmatic injury. There were 6 (27.3 %) associated
intra-abdominal injuries. Twenty one (95.5 %) of 22 patients with diaphragmatic
injuries were successfully repaired laparoscopically. Mean duration of procedure
with diaphragmatic repair was 74.9 +/- 22.5 min compared to 38.3 +/- 16.9 min
without diaphragmatic repair. Six patients (10.9 %) had minor intra-operative
complications. There were no deaths. Hospital stay was 2.9 +/- 3.4 days.
CONCLUSIONS: Diaphragmatic injury was present in 40 % of patients with left-sided
thoracoabdominal injury. Radiological findings were not reliable in predicting
diaphragmatic injury. The majority of these injuries can be safely repaired
laparoscopically.
PMID- 25125097
TI - Neuromuscular blockade improves surgical conditions (NISCO).
AB - BACKGROUND: We examined the impact of muscle relaxation on surgical conditions
and patients' postoperative outcome during elective laparoscopic cholecystectomy
under balanced anaesthesia. METHODS: After approval and consent, 57 anaesthetized
patients were randomly assigned to group no neuromuscular blockade (No NMB) and
deep neuromuscular blockade (Deep NMB), i.e. no twitch response to train-of-four
nerve stimulation. Laparoscopic cholecystectomy was performed using the 4-trocar
technique with a CO2-pneumoperitoneum. Surgical conditions were assessed using a
Visual Analogue Scale. Movement of diaphragm or abdominal muscles, inadequate
visibility, or breathing and coughing against the ventilator were documented as
events reflecting inadequate muscle relaxation. Independently, surgeons could
request 0.3 mg/kg rocuronium to improve surgical conditions. Workflow variables
were obtained as a surrogate of surgical conditions. Data are presented as mean
(95 % confidence interval). The trial is registered at ClinicalTrials.gov
(NCT00895778). RESULTS: While in 12 of 25 patients of group "No NMB" one or more
adverse events impaired the surgical procedure (p < 0.001), only 1 of 25 patients
of group "Deep NMB" showed an adverse event. Deep NMB resulted in an absolute
risk reduction of 0.44 (0.23-0.65) and a number needed to treat of 2.3 (1.5-4.4),
respectively. Surgeons requested 0.3 mg/kg rocuronium in 10 of 25 cases (40 %) of
group "No NMB" only. This dose significantly improved surgical conditions by an
average 62 of 100 possible points. All further variables did not differ between
groups. CONCLUSIONS: Deep NMB ameliorates surgical conditions for laparoscopic
cholecystectomy by improved visibility and reduction of involuntary movements.
PMID- 25125098
TI - The efficacy of prophylactic IVC filters in gastric bypass surgery.
AB - BACKGROUND: Patients undergoing gastric bypass surgery have a high risk for
thromboembolic events. Over the last decade, the use of prophylactic IVC filters
(IVCF) has drastically increased for patients who are considered high risk.
However, the role and efficacy of prophylactic IVCF placement remain
controversial, and the literature is limited to a few retrospective studies.
METHODS: We conducted a systematic review of the literature. A total of 21
articles were analyzed, and eight relevant retrospective studies were chosen for
review of data. Data from laparoscopic gastric bypass surgery were compared to
open gastric bypass surgery RESULTS: The relevant eight retrospective studies
included a total of 597 patients. Patients had IVCFs before laparoscopic gastric
bypass (41 %) and before open gastric bypass (59 %). There were 5 postoperative
pulmonary emboli (PE) (0.84 %), 21 DVTs (3.52 %), 5 minor IVCF-related
complications (0.84 %), 2 major IVCF-related complications (0.34 %), and 10
deaths (1.68 %). The rate of postoperative PE was the same in the laparoscopic
group and the open group (0.84 %). The rate of DVT in the laparoscopic group was
5.02 %, and in the open group, it was 2.23 %. CONCLUSION: It is estimated that 55
% of bariatric surgeons use IVCF in high-risk patients. Prospective research that
supports the use of IVCF is very limited, and individualized placement relies on
retrospective studies only. In addition, patient characteristics associated with
high risk vary between different studies. Our review showed that most of the
published studies support the use of prophylactic IVCF and found it to be safe.
On the other hand, the largest and most recent retrospective cohort study does
not support their use. The efficacy of prophylactic IVCFs before gastric bypass
surgery in high-risk patients has not been established.
PMID- 25125099
TI - Comparative analysis of the functionality of simulators of the da Vinci surgical
robot.
AB - BACKGROUND: The implementation of robotic technology in minimally invasive
surgery has led to the need to develop more efficient and effective training
methods, as well as assessment and skill maintenance tools for surgical
education. Multiple simulators and procedures are available for educational and
training purposes. A need for comparative evaluations of these simulators exists
to aid users in selecting an appropriate device for their purposes. METHODS: We
conducted an objective review and comparison of the design and capabilities of
all dedicated simulators of the da Vinci robot, the da Vinci Skill Simulator
(DVSS) (Intuitive Surgical Inc., Sunnyvale, CA, USA), dV-Trainer (dVT) (Mimic
Technologies Inc., Seattle, WA, USA), and Robotic Surgery Simulator (RoSS)
(Simulated Surgical Skills, LLC, Williamsville, NY, USA). This provides base
specifications of the hardware and software, with an emphasis on the training
capabilities of each system. RESULTS: Each simulator contains a large number of
training exercises, DVSS = 40, dVT = 65, and RoSS = 52 for skills development.
All three offer 3D visual images but use different display technologies. The DVSS
leverages the real robotic surgeon's console to provide visualization, hand
controls, and foot pedals. The dVT and RoSS created simulated versions of all of
these control systems. They include systems management services which allow
instructors to collect, export, and analyze the scores of students using the
simulators. CONCLUSIONS: This study is the first to provide comparative
information of the three simulators functional capabilities with an emphasis on
their educational skills. They offer unique advantages and capabilities in
training robotic surgeons. Each device has been the subject of multiple
validation experiments which have been published in the literature. But those do
not provide specific details on the capabilities of the simulators which are
necessary for an understanding sufficient to select the one best suited for an
organization's needs.
PMID- 25125100
TI - Transoral periosteal thyroidectomy: cadaver to human.
AB - BACKGROUND: Although endoscopic thyroid surgery is gaining wide acceptance,
existing endoscopic methods for thyroidectomy are blamed for the increased
frequency of flap dissections and longer surgical times. More recently, transoral
endoscopic thyroidectomy has overcome the limitations of previous approaches.
Herein, we present our initial experience with transoral periosteal thyroidectomy
(TOPOT) in cadaver and porcine models. Using these models, the surgical view was
improved and had greater freedom of motion; the technique was then performed in
human subjects using robotic TOPOT, which has not previously been reported.
METHOD: TOPOTs were performed in seven fresh human cadavers and ten live pigs.
Total thyroidectomies were performed in all cadavers and pigs. After the cadaver
and animal trials, four human patients underwent robotic TOPOT performed using
the da Vinci(r) surgical system at Korea University Anam Hospital. Recurrent
laryngeal nerve function, intra- and postoperative complications, and
postoperative outcomes were assessed in all patients. RESULT: One left lobectomy
for follicular adenoma, two right lobectomies for nodular hyperplasia, and one
left lobectomy with a central neck dissection for papillary thyroid
microcarcinoma were performed in the human subjects using a robotic transoral
periosteal approach. In three cases, paresthesia occurred in the mental nerve,
but this improved within 4 weeks in all cases. No local infections occurred at
the incision site or anterior neck, and no recurrent laryngeal nerve cord palsies
occurred postoperatively. CONCLUSION: TOPOT may be an effective and safe approach
for robotic thyroid surgery.
PMID- 25125101
TI - Laparoscopic Roux-en-Y gastric bypass in the elderly: feasibility, short-term
safety, and impact on comorbidity and weight in 250 cases.
AB - INTRODUCTION: In the elderly obese population, frequently suffering from multiple
comorbidities, laparoscopic Roux-en-Y gastric bypass (LRYGB) is considered a high
risk procedure. The aim of this study was to evaluate short-term safety (30-day
hospital morbidity and mortality) of this procedure and its impact on weight and
associated comorbidities in the medium term (type-two diabetes, hypertension,
sleep apnea, hypercholesterolemia, and joint pain). METHODS: This study
represents a retrospective analysis of all our Belgian patients older than 60
years of age who underwent a LRYGB between October 2004 and October 2012. Patient
files were reviewed and patients were contacted by formal consultation or by
phone for an update of their clinical status. Demographics, operative details,
postoperative course, and the evolution of weight and associated comorbidities
were registered. RESULTS: A total of 280 patients were included. A complete
follow-up was available for 250 patients (89 %), of whom 161 were female and 89
male. Mean age, BMI, and hospital stay were 64.1 years (60-78 years), 41.9
kg/m(2) (27.4-68 kg/m(2)), and 4.3 days (2-19 days), respectively. There was no
in-hospital mortality, 27 (10.8 %) patients suffered from early postoperative
complications and 5 (2 %) patients needed to be readmitted. After a mean follow
up of 31.5 months, the mean excess weight loss was 59.3 % (range 21.9-120.1 %).
Resolution or improvement of diabetes, hypertension, sleep apnea,
hypercholesterolemia, and joint pain was seen in 94.6, 77.6, 88.0, 77.1 and 57.6
% respectively. CONCLUSION: LRYGB has an acceptable complication rate in the
elderly. Since all obesity-related comorbidities improved during follow-up, there
is a plea not to exclude this subgroup of patients from the well-known benefits
of gastric bypass surgery.
PMID- 25125102
TI - Retention of fundamentals of laparoscopic surgery (FLS) proficiency with a
biannual mandatory training session.
AB - BACKGROUND: The fundamentals of laparoscopic surgery (FLS) program was developed
by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) in
1997 with the goal of teaching surgeons the fundamental knowledge, judgment, and
technical skills specific to laparoscopic surgery (Peters et al., Surgery JH
135:21-27, 2004; Soper et al., Bull Am College Surg NJ 93:30-32, 2008). This
single academic institution observational study aimed to assess the effectiveness
of a biannual FLS training curriculum on Post-Graduate Year [PGY] 1-5 proficiency
levels, with a focus on one FLS task (PEG transfer). Previous studies have shown
that obtaining expert FLS proficiency correlates with retaining proficiency in
the future (Castellvi et al., Surgery 146:387-393, 2009). METHODS: PGY 1-5
residents (n = 28) at an academic general surgery residency program performed two
timed PEG transfer tasks biannually. Participants were monitored by FLS certified
examiners and standard FLS rules applied. Residents were expected to meet or
exceed standards set by SAGES and FLS in consecutive timed PEG transfer trials
(proficiency: <48 s). RESULTS: Twenty-eight residents participated (PGY 1-5).
Participants showed proficiency if they completed the PEG transfer task in less
than 48 s on two consecutive trials. None of the PGY 1 or PGY 2 residents
completed two consecutive trials within the stated proficiency time, while the
majority of the PGY 3-5 residents showed proficiency in the PEG transfer task.
CONCLUSION: A biannual training session for FLS retains expert proficiency by PGY
levels 4-5. Previous reports from our institution demonstrated that 95 % of the
residents did not practice this task between mandatory biannual sessions. This
suggests that, in combination with standard residency training, biannual FLS
sessions confer retained expert skills by PGY 4-5. As the FLS exam is generally
taken by PGY 4 and 5 residents and is required for board certification, general
surgery residents that participate in biannual training sessions will likely
retain expert proficiency and achieve FLS certification.
PMID- 25125104
TI - Rotating ring-disk electrode with dual dynamic potential control: theory and
practice.
AB - Using the LabVIEWTM graphical programming language designed by National
Instruments(r), a digital simulation model has been developed in order to
describe electrochemical processes occurring at rotating ring-disk electrodes.
The model allows for taking into consideration independent potential control of
the two working electrodes, homogeneous electrode reactions, as well as spatial
inhomogeneities of the working electrode surfaces. The main programming concepts,
as well as the operation of the simulation software is presented. Several test
simulations have been carried out in order to evaluate the accuracy of the
calculations.
PMID- 25125103
TI - Interactions of divalent calcium ions with head groups of zwitterionic
phosphatidylcholine liposomal membranes.
AB - The interaction of the divalent calcium ions with the zwitterionic lipid
membranes was studied by measuring the lipid order parameter which is inversely
proportional to the membrane fluidity. Small unilamellar lipid vesicles were
prepared from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and then treated
with different concentrations of divalent calcium ions. An increase in the order
parameter and decrease in the fluidity of the liposomal membranes were observed
after treatment with the calcium ions. The presence of positively charged iron
oxide nanoparticles in the suspension of liposomes negligibly changed the
results. The results of experiments were discussed theoretically within modified
Langevin-Poisson-Boltzmann (MLPB) model leading to the conclusion that the
membrane fluidity and ordering of the membrane lipids are primarily altered by
the accumulation of calcium ions in the region of negatively charged phosphate
groups within the head groups of the membrane lipids.
PMID- 25125105
TI - Electrochemical reduction of perchlorate ions on ruthenium.
AB - The reduction of perchlorate ions at ruthenium electrodes was investigated by
voltammetry, chronoamperometry, impedance spectroscopy, and by measuring changes
of interfacial stress changes using the cantilever bending method as functions of
electrode potential, and concentrations of perchloric acid and HCl. The cyclic
voltammograms recorded at a rotating (Ru) disc electrode were highly asymmetric
with respect to the electrode potential axis, and a negative current could be
observed even during the positive sweep. Chloride ions decrease the interfacial
stress and exert an inhibiting effect on the reduction process indicating the
role of competitive adsorption. The desorption rate of Cl(-) depends strongly on
the hydrodynamic conditions, probably through desorption/diffusion coupling.
These results serve as a warning that in perchlorate-containing solutions in
contact with Ru the adsorption of chloride ions may also influence the rate of
other electrochemical processes.
PMID- 25125106
TI - Relative permittivity in stern and diffuse layers.
AB - Stern layer and outer Helmholtz plane (i.e. the distance of closest approach) are
considered within electric double layer models, where the orientational ordering
of water dipoles is explicitly taken into account. It is shown that permittivity
of the Stern layer is not independent of the surface charge density as it is
frequently assumed in different theoretical models and simulations, but strongly
depends on the magnitude of the surface charge density. Therefore, to predict the
behaviour and realistic values of the surface potential and electric field, in
the electrolyte solution near the charged surface, requires a surface charge
density dependent permittivity of the Stern layer.
PMID- 25125107
TI - Mechanism of electroreduction of the Henry reaction products. Electrochemically
initiated degradation of 1-phenyl-2-nitroethanol.
AB - Electroreduction of the Henry reaction product - i.e. 1-phenyl-2-nitroethanol
(PNE) - in 0.1 M Bu(4)NClO(4) solution in MeCN has been investigated by a set of
experimental (cyclic voltammetry, chronoamperometry, and controlled potential
electrolysis) and theoretical (digital simulation and quantum chemical
calculations) methods. The results obtained show that cathodically generated
radical anion of PNE undergoes C-C bond cleavage reaction resulting in the
formation of the free radical of benzyl alcohol and nitromethane anion. The
proton transfer between these species affords nitromethane and benzaldehyde
radical anion. Electron transfer from the last to PNE initiates the cyclic
process of the PNE degradation.
PMID- 25125108
TI - Permittivity spectroscopy - an insight into materials properties.
AB - Permittivity Spectroscopy is a branch of the Impedance Spectroscopy specially
tuned for measurements and analyses of dielectrics permittivity properties. The
present paper presents experimental results on permittivity properties of
composite objects in which a polarizable dielectric is distributed in a fine non
polarizable matrix (solid or liquid) measured in frequency range 1 MHz down to
0.01 Hz. Two types of objects are studied - water in porous functional ceramics
and lubricating oils. In both systems gigantic enhancement of the effective
capacitance is observed. The first series of experiments was performed on porous
membranes of yttrium doped barium cerate, which is a proton conducting ceramics
with hydrophilic properties. At a given level of watering the measured
capacitance is sharply increasing (3 to 5 orders of magnitude) in the lower
frequency range. The second example covers permittivity study of lubricating
oils, where the increase is 2-3 orders of magnitude. The phenomenon of gigantic
enhancement of the effective capacitance could be related to a formation of
dipole volume structures induced by the external alternating electrical field.
PMID- 25125109
TI - Electrodeposition of Co/CoO nanoparticles onto graphene for ORR electrocatalysis:
a study based on micro-X-ray absorption spectroscopy and X-ray fluorescence
mapping.
AB - Electrodeposition of graphene-supported Co for ORR electrocatalysts from an
acetonitrile solution has been studied by a multi-technique approach, combining a
suite of spectroscopic methods with electrochemical measurements, allowing a
molecular-level understanding of potentiostatic and pulsed-potential plating
processes from the organic solvent onto a freestanding graphene film. The
formation of the graphene film by the light-scribe approach has been monitored by
Raman spectroscopy; the electrodeposition process has been clarified by cyclic
voltammetry and the compositional and chemical-state distribution of Co have been
investigated ex situ by soft X-ray absorption spectroscopy and fluorescence
mapping, showing that both spatial distribution and valence state are homogeneous
and independent of the local current density. The deposit consists in micrometric
aggregates of Co/CoO nanoparticles with diameter ca. 30 nm (pulsed) and 200 nm
(potentiostatic deposition). Potentiostatic deposition allows to obtain better
ORR electrocatalytic perfomance in terms of nnumber of transferred electrons,
onset/ half-wave potential and current density.
PMID- 25125110
TI - Some factors influencing power and energy capabilities of RuO2 supercapacitors.
AB - Ruthenium oxide electrodes prepared by different routes were studied and the
results discussed in terms of the possibility of using these electrodes in high
power/high energy supercapacitors. The supercapacitor electrodes were prepared by
mixing RuO(2) particles with a binder (Nafion((r)) or polyvinilydenfluoride) in
various ratios. The results show that charging/discharging reaction of RuO(2)
consists of at least two redox reactions taking place simultaneously at different
rates. The contribution of each reaction in the overall process depends on the
hydration of RuO(2) as well as on the type of binder and binder/RuO(2) ratio.
From both energy and power capability of supercapacitors the best electrode
composition would be hydrous RuO(2) with ~20% Nafion((r)) as a binder. Asymmetric
supercapacitors assembled with RuO(2) and activated carbon as a counter electrode
gave 26 and 12 W h kg(-1) at average specific power of 5 W g(-1) for
RuO(2)/Nafion((r)) and RuO(2)/polyvinylidene fluoride, respectively.
PMID- 25125111
TI - Stability of commercial Pt/C low temperature fuel cell catalyst: electrochemical
IL-SEM study.
AB - Platinum catalyst stability has been investigated under potentiostatic and
potentiodynamic conditions with and without the presence of chloride anions. The
combination of rotating disc electrode (RDE) and identical location scanning
electron microscopy (IL-SEM) methods reveals that potentiodynamic degradation is
much more severe compared to the potentiostatic and that chloride enhances
platinum dissolution thus catalyst degradation. IL-SEM method nicely shows the
platinum dissolution and redeposition on the top of a catalyst film.
PMID- 25125112
TI - An innovative hybrid 3D analytic-numerical model for air breathing parallel
channel counter-flow PEM fuel cells.
AB - The parallel straight channel PEM fuel cell model presented in this paper extends
the innovative hybrid 3D analytic-numerical (HAN) approach previously published
by the authors with capabilities to address ternary diffusion systems and counter
flow configurations. The model's core principle is modelling species transport by
obtaining a 2D analytic solution for species concentration distribution in the
plane perpendicular to the cannel gas-flow and coupling consecutive 2D solutions
by means of a 1D numerical pipe-flow model. Electrochemical and other nonlinear
phenomena are coupled to the species transport by a routine that uses derivative
approximation with prediction-iteration. The latter is also the core of the
counter-flow computation algorithm. A HAN model of a laboratory test fuel cell is
presented and evaluated against a professional 3D CFD simulation tool showing
very good agreement between results of the presented model and those of the CFD
simulation. Furthermore, high accuracy results are achieved at moderate
computational times, which is owed to the semi-analytic nature and to the
efficient computational coupling of electrochemical kinetics and species
transport.
PMID- 25125113
TI - Rigid- and polarizable-ion potentials for modeling Ru-polyoxometalate catalysts
for water oxidation.
AB - This work assesses the predictive power and capabilities of classical interatomic
potentials for describing the atomistic structure of a fully inorganic water
oxidation catalyst in the gas phase and in solution. We address a Ru
polyoxometalate molecule (Ru-POM) that is presently one of the most promising
catalysts for water oxidation due to its efficiency and stability under reaction
conditions. The Ru-POM molecule is modeled with two interatomic potentials, the
rigid ion model and the shell model potentials, which are used to perform
molecular dynamics simulations. The predictions of these two approaches are
discussed and compared to the available ab-initio data. These results allow us to
establish the suitable level of theory to model complex heterogeneous interfaces
between the Ru-POM and electrodes in solution.
PMID- 25125114
TI - Corrosion evaluation of zirconium doped oxide coatings on aluminum formed by
plasma electrolytic oxidation.
AB - The plasma electrolytic oxidation (PEO) of aluminum in sodium tungstate
(Na(2)WO(4) . (2)H(2)O) and Na(2)WO(4) . (2)H(2)O doped with Zr was analyzed in
order to obtain oxide coatings with improved corrosion resistance. The influence
of current density in PEO process and anodization time was investigated, as well
as the influence of Zr, with the aim to find out how they affect the chemical
content, morphology, surface roughness, and corrosion stability of oxide
coatings. It was shown that the presence of Zr increases the corrosion stability
of oxide coatings for all investigated PEO times. Evolution of EIS spectra during
the exposure to 3% NaCl, as a strong corrosive agent, indicated the highest
corrosion stability for PEO coating formed on aluminum at 70 mA/cm(2) for 2 min
in a zirconium containing electrolyte.
PMID- 25125115
TI - Structure and dielectric properties of electrochemically grown ZrO2 films.
AB - The dielectric properties of electrochemically grown zirconium oxide films by
anodisation of zirconium in 1.0 mol dm-3 phosphoric acid solution were
investigated in a 3 to 30 V potential range with a view to inducing surface
modifications for eventual use in biomedical and electronic applications. The
oxide films grown at different potentials were characterised by Atomic Force
Microscopy, X-ray photoelectron and Raman spectroscopies; the latter demonstrated
the incorporation of phosphate ions into the passive films. Flat band potentials
calculated from the Mott-Shottky analysis of the oxides semiconducting properties
confirm the bilayer structure of the films. The oxide dielectric permittivity was
evaluated from impedance spectroscopy measurements and the film oxide model
proposed gave values independent of the oxide growth potential.
PMID- 25125116
TI - Optimizing the preparation procedure of self-assembled monolayer of stearic acid
for protection of cupronickel alloy.
AB - The aim of this work is to examine the possibility of CuNi protection in chloride
media by self-assembled monolayers (SAMs) of stearic acid (SA). In order to
obtain a compact, well ordered monolayer, that will provide long term protection,
different SAM preparation procedures are studied. The influence of CuNi
pretreatment, SA solution temperature and temperature of the drying period
followed after the SA treatment on the protective properties of stearic acid self
assembled layer are examined by electrochemical methods and surface analysis
techniques. The obtained results show that for complete self-assembled film
formation it is necessary to have a drying period after exposing the sample to
the stearic acid solution. Heating of the SA solution and drying period at higher
temperatures result in layers with better stability in chloride media. The most
compact surface layer, that provides long lasting and efficient protection to the
underlying alloy, is obtained when prior to SA solution exposure an oxide layer
on CuNi surface was formed at elevated temperatures.
PMID- 25125117
TI - Molecular modeling of organic corrosion inhibitors: why bare metal cations are
not appropriate models of oxidized metal surfaces and solvated metal cations.
AB - The applicability of various models of oxidized metal surfaces - bare metal
cations, clusters of various size, and extended (periodic) slabs - that are used
in the field of quantum-chemical modeling of corrosion inhibitors is examined and
discussed. As representative model systems imidazole inhibitor, MgO surface, and
solvated Mg(2+) ion are considered by means of density-functional-theory
calculations. Although the results of cluster models are prone to cluster size
and shape effects, the clusters of moderate size seem useful at least for
qualitative purposes. In contrast, the bare metal cations are useless not only as
models of oxidized surfaces but also as models of solvated cations, because they
bind molecules several times stronger than the more appropriate models. In
particular, bare Mg(2+) binds imidazole by 5.9 eV, while the slab model of
MgO(001) by only 0.35 eV. Such binding is even stronger for 3+ cations, e.g.,
bare Al(3+) binds imidazole by 17.9 eV. The reasons for these fantastically
strong binding energies are discussed and it is shown that the strong bonding is
predominantly due to electron charge transfer from molecule to metal cation,
which stems from differences between molecular and metal ionization potentials.
PMID- 25125118
TI - Correlation between electronic and corrosion properties of the passive oxide film
on nitinol.
AB - The oxide film (TiO(2)) was formed on Nitinol potentiostatically in an acetic
acid solution. Deep understanding of electronic properties of this film is needed
to predict long-term corrosion properties of Nitinol implant material in
simulated body fluid conditions. The capacitance measurements were performed
under depletion conditions to study electronic (semiconducting) properties. The
space charge, formed at the solid|liquid interface, creates the barrier for the
corrosion processes in aggressive (bio)environment. According to the results of
electrochemical impedance spectroscopy (EIS) and Mott-Schottky analysis (MS), the
passive film on Nitinol behaves as amorphous highly-doped n-type semiconductor.
The values of electronic structure parameters (the flat-band potential, E(fb) and
the carrier (donor) density, N(D)) were corrected for frequency dispersion.
PMID- 25125119
TI - Preparation and characterization of poly(5-aminoindole) by using electrochemical
quartz crystal nanobalance technique.
AB - The electrochemical quartz crystal nanobalance (EQCN) was employed to study the
electropolymerization of 5-aminoindole on platinum electrodes in acidic media.
Potentiostatic or potential cycling electrooxidation of 5-aminoindole below 0.62
V vs. SCE leads to the formation of uniform, yellow, electrochemically active
polymeric films. A scheme of the redox transformations of poly(5-aminoindole)
which involves protonation-deprotonation steps accompanying the electron transfer
is suggested. At higher positive potentials, further oxidation takes place
resulting in different blue-purple, indigo-type materials which remain attached
to the metal surface but show decreased or no redox activity.
PMID- 25125120
TI - Impedance of electrochemically modified graphite.
AB - Electrochemical impedance spectroscopy, EIS, has been applied for
characterization of electrochemically modified graphite electrodes in the
sulphuric acid solution. Graphite modifications were performed by potential
cyclization between potentials of graphite oxide formation/reduction, different
number of cycles, and prolonged reduction steps after cyclization. Impedance
spectra measured at two potential points within double-layer region of graphite
have been successfully modeled using the concept of porous electrodes involving
two different electrolyte diffusion paths, indicating existence of two classes of
pores. The evaluated impedance parameter values show continuous changes with
stages of graphite modification, indicating continuous structural changes of
pores by number of potential cycles applied. Differences of impedance parameter
values at two potential values indicate the potential induced changes of solution
properties within the pores of modified graphite.
PMID- 25125121
TI - Incorporation of cobalt-ferrite nanoparticles into a conducting polymer in
aqueous micellar medium: strategy to get photocatalytic composites.
AB - In this study an easy strategy for conducting polymer based nanocomposite
formation is presented through the deposition of cobalt-ferrite (CoFe(2)O(4))
containing poly(3,4-ethylenedioxythiophene) (PEDOT) thin layers. The
electrochemical polymerization has been performed galvanostatically in an aqueous
micellar medium in the presence of the nanoparticles and the surface active
Triton X-100. The nanoparticles have been characterized by Transmission electron
microscopy (TEM), the thin layers has been studied by applying Scanning electron
microscopy (SEM), and X-ray diffraction (XRD), and the basic electrochemical
properties have been also determined. Moreover, electrocatalytic activity of the
composite was demonstrated in the electrooxidation reaction of dopamine (DA). The
enhanced sensitivity - related to the cobalt-ferrite content - and the
experienced photocatalyitic activity are promising for future application.
PMID- 25125122
TI - Electronic absorption spectra and nonlinear optical properties of ruthenium
acetylide complexes: a DFT study toward the designing of new high NLO response
compounds.
AB - In this study we have used density functional theory (DFT) to calculate nonlinear
optical properties and simulate the UV-VIS absorption spectra of ruthenium
acetylide complexes.Among the studied systems, system 4 has shown highest non
linear optical properties (a = 72.92 * 10(-24)esu and b = 76.32 * 10(-30)esu).New
compounds have been theoretically designed by the extension of conjugation length
and substitution of electron withdrawing atom/groups as acceptor on system 4. All
designed compounds show intense band due to metal-to-ligand charge transfer
(MLCT).Second-order polarizabilityof new design compounds was remarkablyhigh as
compared to system 4 (123.35 * 10(-30)to 360.23 * 10(-30)esu). Effect of
acceptors was more prominent than pi-spacers. Results of theoretical
investigation indicate that all systems should be excellent non-linear optical
materials.
PMID- 25125123
TI - Effects of different gas phases and gas bubbles on the nucleation kinetics.
AB - In this study, the effects of different gas phases and gas bubbles on the
Induction time were investigated. In the first step, the effects of different
kinds of gases (N(2), Ar, dry air-N(2) and dry air-Ar) which are fed into
solution-gas interphase and into the solution were determined. After determining
the most effective gas upon the Induction time, the next step was to use this gas
in the presence of the seed crystals, to specify variation in the Induction time.
The experimental results show that gassing and the presence of seed crystal tend
to shorten the Induction time as compared to the normal crystallization
condition.
PMID- 25125125
TI - Photodegradation of 4-methylphenol on palladium phthalocyaninesulfonate
functionalized mesopolymer under visible light irradiation.
AB - A versatile photocatalyst has been prepared by grafting palladium
phthalocyaninesulfonate (PdPcS) onto the FDU-14 mesopolymer with 3-D cubic
mesostructure (FDU-14-PdPcS) via multi-step chemical modification processes. The
FDU-14-PdPcS was characterized by the X-ray diffraction (XRD), diffuse
reflectance UV-vis spectroscopy and inductively coupled plasma (ICP) techniques.
In the photodegradation studies of 4-methylphenol, the FDU-14-PdPcS catalyst
exhibited excellent visible light photocatalytic activity and reusability in the
present of H(2)O(2). The photodegradation intermediate of 4-methylphenol was
investigated by gas chromatoghraphy-mass spectrometry (GC-MS) technique.
Quenching experiments with isopropanol, sodium azide and benzoquinone suggested
that (1)O(2) and O(2)(*-) were the prominent active species during the
photodegradation process. A possible mechanism involved in the photodegradation
of 4-methylphenol has also been discussed.
PMID- 25125124
TI - Adsorptive stripping voltammetry of antibiotics rifamycin SV and rifampicin at
renewable pencil electrodes.
AB - Adsorptive stripping voltammetry of antibiotics of rifamycin SV (RSV) and
rifampicin (RIF) was investigated by cyclic voltammetry and differential pulse
voltammetry using a renewable pencil graphite electrode (PGE). The nature of the
oxidation process of RSV and RIF taking place at the PGE was characterized. The
results show that the determination of highly sensitive oxidation peak current is
the basis of a simple, accurate and rapid method for quantification of RSV and
RIF in bulk forms, pharmaceutical formulations and biological fluids by
differential pulse adsorptive stripping voltammetry (DPASV). Factors influencing
the trace measurement of RSV and RIF at PGE are assessed. The limits of detection
for the determination of RSV and RIF in bulk forms are 6.0 * 10(-8) mol/L and 1.3
* 10(-8) mol/L, respectively. Moreover, the proposed procedure was successfully
applied to assay both RSV and RIF in pharmaceutical formulations and in
biological fluids. The capability of the proposed procedure for simultaneous
assay of antibiotics RSV-isoniazid and RIF-isoniazid was achieved. The
statistical analysis and calibration curve data for trace determination of RSV
and RIF are reported.
PMID- 25125126
TI - Polymer nanoparticles containing 2,4,6-triiodophenol: a potential contrast medium
for medical imaging.
AB - Contrast agents have been utilized for x-ray imaging to visualize blood vessels.
Triiodobenzene derivatives are known contrast agents yet have not been formulated
in a nanoparticle form for the purpose of enhancing the contrast of cancer
tissues. In this study, experiments to encapsulate 2,4,6-triiodophenol in a
polymer matrix were designed. Spherical NPs made of PLA, PLGA, PLA-TPGS, PLGA
TPGS and TPGS-FOL, were synthesized and characterized. Using the oil-in-water
single-emulsion technique, the effect of several experimental parameters such as
sonication power, ratio of 2,4,6-triiodophenol/polymer, type and concentration of
emulsifier, and polymer type has been studied. A good morphology of polymer NPs
with entrapped 2,4,6-triiodophenol was successfully obtained however the
encapsulated iodine was in the range of 5 to 26%.
PMID- 25125127
TI - Synthesis of 3',4'-dihydro-2H,2'H,5H-spiro [imidazolidine-4,1'-naphthalene]-2,5
dione and its derivatives.
AB - The synthesis of two novel compounds, 1-amino-3',4'-dihydro-2H,2'H,5H
spiro[imidazolidine-4,1'-naphthalene]-2,5-dione and 1,3-bis(hydroxymethyl)-3',4'
dihydro-2H,2'H,5H-spiro[imidazolidine-4,1'-naphthalene]-2,5-dione, was reported.
The structures of the compounds were verified by (1)H, (13)C NMR and IR
spectroscopy and quantum-chemical calculations at DFT level.
PMID- 25125128
TI - Colchicine levels in chronic kidney diseases and kidney transplant recipients
using tacrolimus.
AB - BACKGROUND: Tacrolimus is a CYP3A4 inhibitor and can alter colchicine metabolism.
In this study, we aimed to evaluate plasma colchicine levels in different stages
of kidney disease as well as in kidney transplant (KTx) recipients using
tacrolimus. METHOD: This study included six familial Mediterranean fever (FMF)
patients with normal glomerular filtration rate (GFR) as controls, three patients
with low GFR, six FMF patients on hemodialysis (HD), and six FMF patients who
were KTx recipients using tacrolimus. After a three-d washout period, plasma
colchicine levels were measured at 0 (pre-dose), one, two, four, eight, and 24 h
post-dose of 1 mg oral colchicine. Area under the curve 0-24 h (AUC0-24 ) and
maximum concentration (Cmax ) were evaluated and compared between the groups.
RESULTS: Colchicine AUC0-24 was six-fold higher in HD (p < 0.001) and three-fold
higher in KTx recipients (p < 0.001) when compared to the control. The low GFR
group had mildly higher AUC0-24 than the control group. Cmax levels were also
higher in HD (p = 0.011) and KTx recipient (p = 0.06) groups and mildly elevated
in low GFR patients in comparison with controls. CONCLUSION: Colchicine AUC0-24
and Cmax were significantly increased in HD patients and KTx recipients using
tacrolimus. Therefore, dose adjustments are needed to avoid toxicity in both
circumstances.
PMID- 25125129
TI - Flow cytometry-based assay to study HIV-1 gp120 specific antibody-dependent
cellular cytotoxicity responses.
AB - Increased attention on the role of Fc-mediated effector functions against HIV-1
has led to renewed interest into the role that antibody-dependent cellular
cytotoxicity (ADCC) could play in controlling viral transmission and/or the rate
of disease progression. While (51)Chromium release assays have traditionally been
used to study ADCC responses against HIV-1, a number of alternative flow
cytometry-based assays were recently developed. In this study, an alternative
flow-cytometry-based assay was established to allow non-radioactive measurement
of ADCC-mediated elimination of HIV-1 gp120 envelope glycoprotein (Env)-coated
target cells. This assay relies on staining target and effector cells with
different dyes, which allows precise gating and permits the calculation of the
number of surviving target cells by normalization to flow-cytometry particles. By
using small concentrations of recombinant gp120 Env, suitable targets cells that
recapitulate the ADCC response mediated against HIV-1-infected cells were
generated. Finally, this method was applied successfully to screen human sera for
ADCC activity directed against HIV-1 gp120 Env.
PMID- 25125131
TI - Guest editorial: sleepers awake! Older people are our future (or beige is the new
black).
PMID- 25125130
TI - Optimal transfection methods and comparison of PK-15 and Dulac cells for rescue
of chimeric porcine circovirus type 1-2.
AB - A chimeric porcine circovirus type 1-2 (PCV1-2) infectious DNA clone has low
transfection efficiency and exhibits low levels of proliferation. Electroporation
and lipofection parameters were optimized for PK-15 and Dulac cells with the
purpose of increasing the efficiency for rescuing infectious PCV1-2. Titers of
PCV1-2 in Dulac cells were 100-fold higher than those in PK-15 cells following
transfection. The electroporation efficiency into Dulac cells was high when three
400 MUs pulses at 250 V with 6 MUg of plasmid DNA was used, lipofection
efficiency was high when the ratio of DNA to transfection reagent was 1:3. The
proportion of infected cells was 55.6% compared with 44.2%, for the
electroporation and lipofection techniques respectively. Virus titers were higher
in Dulac cells, from 10(4.44) to 10(5.32)TCID50/mL compared with 10(1.90)
10(3.38)TCID(50)/mL for PK-15 cells. Dulac cells were more permissive to PCV1-2
than PK-15 cells regardless of the transfection technique.
PMID- 25125132
TI - Laser all-ceramic crown removal-a laboratory proof-of-principle study-phase 1
material characteristics.
AB - BACKGROUND AND OBJECTIVES: The removal of all-ceramic crowns is a time consuming
and destructive procedure in the dental office. The removal of all-ceramic crowns
using Er:YAG lasers has not been previously described in the scientific
literature. The objective of this laboratory proof-of-principle study was to
evaluate whether with regards to absorption and transmission characteristics of
bonding cements and ceramics all-ceramic crowns can be removed from natural teeth
using an Erbium laser. STUDY DESIGN/MATERIALS AND METHODS: The Fourier Transform
Infrared Spectroscopy (FTIR) was used on flat ceramic samples (IPS Empress
Esthetic (EE), E.max CAD, and E.max ZirCAD) to assess which infrared laser
wavelengths transmit through the ceramics. Additionally, FTIR spectra for four
bonding cements (Variolink Veneer, Variolink II, Multilink Automix, and SpeedCEM)
were obtained. The Er:YAG laser energy transmission (wavelength 2,940 nm, 10 Hz
repetition rate, pulse duration 100 us at 126 mJ/pulse to 300 us at 508 mJ/pulse)
through different ceramic thicknesses was measured. Ablation thresholds for
bonding cements were determined. Cement samples were directly irradiated or laser
light was transmitted through ceramic samples. RESULTS: While the ceramics did
not show any characteristic water absorption bands in the FTIR, all bonding
cements showed a broad H2 O/OH absorption band. Some cements exhibited a distinct
absorption peak at the Er:YAG laser emission wavelength. Depending on the ceramic
thickness, EE and E.max CAD ceramics transmitted between 21 and 60% of the
incident Er:YAG energy, with E.max CAD transmitting more energy than EE at
comparable thicknesses. In contrast, E.max ZirCAD transmitted only 5-10% of the
incident energy. Initial signs of cement deterioration occurred at 1.3-2.6
J/cm(2) . Multilink Automix, SpeedCEM, and Variolink II started ablation at 4.4
4.7 J/cm(2) . Variolink Veneer needed 44% less energy for ablation. CONCLUSION:
Er:YAG laser energy can be transmitted through all-ceramic materials and those
transmitted energies are sufficient for ablation of bonding cements.
PMID- 25125133
TI - The effect of IL-17 on the production of proinflammatory cytokines and matrix
metalloproteinase-1 by human periodontal ligament fibroblasts.
AB - OBJECTIVES: To investigate the effects of IL-17 on IL-6, IL-1beta, and matrix
metalloproteinase (MMP-1) production, and to compare the MMP-1 production between
the individual and combined effects of IL-1beta and IL-6 in human periodontal
ligament fibroblasts (HPDLF). MATERIALS AND METHODS: Human periodontal ligament
fibroblasts were cultured with IL-17 for 0.5, 1, 4, 24, 48, and 72 h, and were
cultured with IL-1beta, IL-6/sIL-6R, or a combination of IL-1beta and IL-6/sIL-6R
for 24 h. To measure the mRNA levels of IL-6, IL-1beta, and MMP-1, total RNA was
extracted from the cultured HPDLF, and a real-time PCR analysis was performed.
The protein levels of IL-6, IL-1beta, and MMP-1 in supernatants were measured
using enzyme-linked immunosorbent assays (ELISAs). RESULTS: IL-17 significantly
increased the expression of IL-6 and MMP-1 mRNA and protein, while IL-17
transiently increased the expression of IL-1beta mRNA. The combination of IL
1beta and IL-6/sIL-6R induced significantly higher levels of MMP-1 protein than
IL-1beta alone. CONCLUSIONS: IL-17 upregulated the production of IL-6 and MMP-1
sequentially in HPDLF. IL-6/sIL-6R may enhance the effects of IL-1beta on MMP-1
production. The present results suggest that IL-17 induces MMP-1 production not
only directly, but also indirectly by promoting IL-6 production, thus resulting
in the degradation of collagens in the PDL.
PMID- 25125134
TI - An extrafacial amelanotic lentigo maligna of the leg: a case report.
PMID- 25125135
TI - Prevalence of sinonasal disease in children with Juvenile idiopathic arthritis.
AB - OBJECTIVES/HYPOTHESIS: Juvenile idiopathic arthritis (JIA) is the most common
chronic rheumatic disease in children and is caused by a multitude of well
studied disorders. However, the association between JIA and/or its treatment and
sinonasal inflammatory disease (SNID) has never been studied. We therefore
investigated this relationship to gain more insight into burdening pathologies
connected to JIA. STUDY DESIGN: Retrospective evaluation. METHODS: A
retrospective evaluation according to the Lund-Mackay score of cone-beam computed
tomography scans (CBCT) performed in 70 children affected by JIA and compared to
CBCT scans of 124 healthy controls was conducted. The prevalence of sinonasal
opacification and adenoid hypertrophy in patients affected with JIA was compared
with findings obtained in unaffected children. RESULTS: JIA was significantly
associated with SNID (P = .030). Of patients with JIA, 18.6% had SNID, whereas in
children without JIA, only 8.1% had SNID. The odds ratio values were 5.38 (95%
confidence interval [CI]: 1.90-15.26) for treated and 0.92 (95% CI: 0.18-4.83)
for untreated JIA. No clear difference was found depending on the duration of
JIA. No association was found between adenoid hypertrophy and SNID (P = .816).
CONCLUSIONS: Our data suggest that JIA patients, especially when undergoing
immunosuppressive therapy, should be subjected to an ear, nose, and throat
evaluation. A prospective study including clinical evaluation would be of the
utmost importance to provide evidence on which to base comprehensive healthcare
for these patients. LEVEL OF EVIDENCE: 3b.
PMID- 25125136
TI - Identification and characterization of a pesticide degrading flavobacterium
species EMBS0145 by 16S rRNA gene sequencing.
AB - Organophosphates (OPs) like chlorpyrifos, diazinon, or malathion have become most
common and indisputably most toxic pest-control agents that adversely affects the
human nervous system even at low levels of exposure. Because of their relatively
low cost and ability to be applied on a wide range of target insects and crop,
organophosphorus pesticides account for a large share of all insecticides used in
India, this in turn raises severe health concerns. In this view, the present
investigation was aimed to identify novel species of Flavobacterium bacteria
which is bestowed with the capacity to degrade pesticides like chlorpyrifos,
diazinon or malathion. The bacterium was isolated from agricultural soil
collected from Guntur District, Andhra Pradesh, India. The samples were serially
diluted and the aliquots were incubated for a suitable time following which the
suspected colony was subjected to 16S rRNA gene sequencing. The sequence thus
obtained was aligned pairwise against Flavobacterium species, which resulted in
identification of novel species of Flavobacterium later which was named as
EMBS0145 and sequence was deposited in GenBank with accession number JN794045.
PMID- 25125137
TI - Association between TNF-alpha-308 G/A gene polymorphism and gastric cancer risk:
a systematic review and meta-analysis.
AB - OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) has been found to be
associated with gastric carcinogenesis, but individually published results have
been inconclusive. The aim of this study was to explore the relationship between
the TNF-alpha-308 G/A polymorphism and gastric cancer risk. METHODS: MEDLINE,
EMBASE and the COCHRANE library databases were searched for relevant articles to
identify all available data. The odds ratios (ORs) with 95% confidence intervals
(95% CIs) from each study were used to assess the association between the TNF
alpha-308 G/A polymorphism and gastric cancer risk. RESULTS: This meta-analysis
included 30 studies (32 datasets) involving 7009 gastric cancer cases and 12,119
control subjects. Overall, a significant association was found between the TNF
alpha-308 G/A polymorphism and gastric cancer in AA+GA vs. GG (dominant contrast
model) (OR=1.20, 95% CI=1.07-1.34, p=0.001). With stratification based on
ethnicity, the TNF-alpha-308 G/A polymorphism was correlated with gastric cancer
risk in Caucasians, using the dominant contrast model (OR=0.74, 95% CI=0.57-0.96,
p=0.02), but not in East Asians and other ethnic groups. In the comprehensive
subgroup analysis, a significant association was also found in recent articles
(published after 2005), population-based high-quality studies, hospital-based
high-quality studies, studies using the TaqMan method and non-cardia subgroups.
However, the TNF-alpha-308 G/A polymorphism was not associated with specific
histological types of gastric cancer risk. CONCLUSIONS: The TNF-alpha-308 G/A
polymorphism may contribute to susceptibility to gastric cancer in Caucasians,
especially for non-cardia gastric cancer, as most strongly demonstrated in high
quality studies and in studies using the TaqMan genotyping method. Furthermore,
we recommend the TaqMan method as the preferred genotyping method in DNA
polymorphism studies.
PMID- 25125139
TI - Influence of gonadotrophin-induced first oestrus on gilt fertility.
AB - The aim of this study was to determine the association between the oestrous
response of pre-pubertal gilts to gonadotrophin injection or boar exposure and
their subsequent farrowing rate and litter size. At 154 days of age, randomly
selected pre-pubertal gilts received an intramuscular injection of 400 IU equine
chorionic gonadotrophin plus 200 IU human chorionic gonadotrophin (PG600((r)) ;
Merck Animal Health; n = 181). From the remaining pool of animals not treated
with hormones, the first gilts showing signs of oestrus were selected to act as
controls (n = 201). Boar exposure began at 155 days of age for both groups, and
gilts were bred at a weight of approximately 130 kg. Comparisons were made
between PG600((r)) -treated gilts exhibiting oestrus or not within 7 days post
injection (early and late responders, respectively) and control gilts exhibiting
oestrus or not within 30 days after beginning of boar exposure (select and non
select control gilts, respectively). By 162 days, oestrus was detected in 67.5%
of PG600((r)) -treated gilts compared with 5.7% of control gilts (p < 0.0001).
The proportion of animals observed in oestrus at least three times before
breeding was greater for select control gilts compared with early and late
responder PG600((r)) -treated gilts (p <= 0.001). There were no significant
differences in farrowing rate and litter size between the four treatment groups.
These data indicate that PG600((r)) is an effective tool to induce an earlier
oestrus in gilts, that subsequent farrowing rate and born alive litter size
compare favourably to that of select gilts and that gilts failing to respond
promptly to hormonal stimulation do not exhibit compromised fertility.
PMID- 25125140
TI - A structured blood conservation programme reduces transfusions and costs in
cardiac surgery.
AB - OBJECTIVES: Transfusions of blood products can be lifesaving, but they are also
associated with considerable risks and adverse effects, including immune response
and infections. In cardiac surgery, transfusions have also been associated with
increased mortality. We prospectively studied the effects of a structured
programme to reduce transfusions and transfusion-associated costs in cardiac
surgery. METHODS: The programme included: (i) education of all staff about the
risks and benefits of blood transfusions; (ii) revised guidelines for
transfusions; and (iii) a transfusion log where indication for transfusion,
status of the patient and prescribing physician were registered. Transfusion
prevalence, complications and costs for blood products were registered for all
acute and elective cardiac operations during a 12-month period before (n = 1128)
and after (n = 1034) the programme was started. The two time periods were
compared. In addition, the prevalence of transfusions was registered for 2 more
years after the programme was initiated. RESULTS: The first year after the
programme was initiated the proportion of patients transfused with red blood cell
concentrate decreased by 21.8% (from 58.2 to 45.5%, P <0.001), plasma by 37.4%
(from 30.8 to 19.3%, P <0.001) and platelets by 21.0% (from 20.5 to 16.2%, P =
0.010). Reoperations for bleeding (5.8 vs 5.0%), early complication rate and 30
day mortality (2.5 vs 2.6%) were not significantly different before and after the
start date. Based on the 2009 institutional prices for red blood cell concentrate
(102 ?/unit), plasma (35 ?/unit) and platelets (290 ?/unit), the savings on blood
products were ?161,623 during the first 12 months after the programme was
launched. The proportion of patients transfused with any blood product was 60.9%
before the programme was started and 48.3, 54.0 and 50.7% 1-3 years after its
start (all P <0.001), respectively. CONCLUSIONS: A structured blood conservation
programme reduces transfusions and costs for blood products in cardiac surgery,
without any signs of compromised medical safety. The effects of introducing such
a programme are maintained over at least 3 years.
PMID- 25125138
TI - Maternal and perinatal outcomes after bariatric surgery: a Spanish multicenter
study.
AB - BACKGROUND: Bariatric surgery (BS) has become more frequent among women of child
bearing age. Data regarding the underlying maternal and perinatal risks are
scarce. The objective of this nationwide study is to evaluate maternal and
perinatal outcomes after BS. METHODS: We performed a retrospective observational
study of 168 pregnancies in 112 women who underwent BS in 10 tertiary hospitals
in Spain over a 15-year period. Maternal and perinatal outcomes, including
gestational diabetes mellitus (GDM), pregnancy-associated hypertensive disorders
(PAHD), pre-term birth cesarean deliveries, small and large for gestational age
births (SGA, LGA), still births, and neonatal deaths, were evaluated. Results
were further compared according to the type of BS performed: restrictive
techniques (vertical-banded gastroplasty, sleeve gastrectomy, and gastric
banding), Roux-en-Y gastric bypass (RYGB), and biliopancreatic diversion (BPD).
RESULTS: GDM occurred in five (3 %) pregnancies and there were no cases of PAHD.
Women whose pregnancies occurred before 1 year after BS had a higher pre
gestational body mass index (BMI) than those who got pregnant 1 year after BS
(34.6 +/- 7.7 vs 30.4 +/- 5.3 kg/m(2), p = 0.007). In pregnancies occurring
during the first year after BS, a higher rate of stillbirths was observed
compared to pregnancies occurring after this period of time (35.5 vs 16.8 %, p =
0.03). Women who underwent BPD delivered a higher rate of SGA babies than women
with RYGB or restrictive procedures (34.8, 12.7, and 8.3 %, respectively).
CONCLUSIONS: Pregnancy should be scheduled at least 1 year after BS.
Malabsorptive procedures are associated to a higher rate of SGA births.
PMID- 25125142
TI - Rhodium(III)-catalyzed C-C and C-O coupling of quinoline N-oxides with alkynes:
combination of C-H activation with O-atom transfer.
AB - [Cp*Rh(III)]-catalyzed C-H activation of arenes assisted by an oxidizing N-O or N
N directing group has allowed the construction of a number of hetercycles. In
contrast, a polar N-O bond is well-known to undergo O-atom transfer (OAT) to
alkynes. Despite the liability of N-O bonds in both C-H activation and OAT, these
two important areas evolved separately. In this report, [Cp*Rh(III)] catalysts
integrate both areas in an efficient redox-neutral coupling of quinoline N-oxides
with alkynes to afford alpha-(8-quinolyl)acetophenones. In this process the N-O
bond acts as both a directing group for C-H activation and as an O-atom donor.
PMID- 25125141
TI - Oesophageal pyomyositis in an intravenous drug user.
AB - An inflammatory or infectious disease of the oesophagus occurring in tissue
layers beneath but sparing the mucosa may pose a diagnostic challenge. Bacterial
pyomyositis has been previously reported occurring mostly in the skeletal muscle.
Pyomyositis involving the gastrointestinal tract is extremely rare, and may
easily be misdiagnosed due to its nonspecific clinical features. We report a case
of an intravenous drug user who presented with oesophageal pyomyositis. Early
computed tomography facilitated accurate diagnosis. Adequate drainage followed by
antibiotic treatment was effective and the oesophagus was preserved. To the best
of our knowledge, this is the first report of a case of oesophageal myositis in
an intravenous drug user.
PMID- 25125143
TI - Highly efficient and excitation tunable two-photon luminescence platform for
targeted multi-color MDRB imaging using graphene oxide.
AB - Multiple drug-resistance bacteria (MDRB) infection is one of the top three
threats to human health according to the World Health Organization (WHO). Due to
the large penetration depth and reduced photodamage, two-photon imaging is an
highly promising technique for clinical MDRB diagnostics. Since most commercially
available water-soluble organic dyes have low two-photon absorption cross-section
and rapid photobleaching tendency, their applications in two-photon imaging is
highly limited. Driven by the need, in this article we report extremely high two
photon absorption from aptamer conjugated graphene oxide (sigma2PA = 50800 GM)
which can be used for highly efficient two-photon fluorescent probe for MDRB
imaging. Reported experimental data show that two-photon photoluminescence
imaging color, as well as luminescence peak position can be tuned from deep blue
to red, just by varying the excitation wavelength without changing its chemical
composition and size. We have demonstrated that graphene oxide (GO) based two
photon fluorescence probe is capable of imaging of multiple antibiotics
resistance MRSA in the first and second biological transparency windows using 760
1120 nm wavelength range.
PMID- 25125144
TI - Chromosomal rearrangements directly cause underdominant F1 pollen sterility in
Mimulus lewisii-Mimulus cardinalis hybrids.
AB - Chromosomal rearrangements can contribute to the evolution of postzygotic
reproductive isolation directly, by disrupting meiosis in F1 hybrids, or
indirectly, by suppressing recombination among genic incompatibilities. Because
direct effects of rearrangements on fertility imply fitness costs during their
spread, understanding the mechanism of F1 hybrid sterility is integral to
reconstructing the role(s) of rearrangements in speciation. In hybrids between
monkeyflowers Mimulus cardinalis and Mimulus lewisii, rearrangements contain all
quantitative trait loci (QTLs) for both premating barriers and pollen sterility,
suggesting that they may have facilitated speciation in this model system. We
used artificial chromosome doubling and comparative mapping to test whether
heterozygous rearrangements directly cause underdominant male sterility in M.
lewisii-M. cardinalis hybrids. Consistent with a direct chromosomal basis for
hybrid sterility, synthetic tetraploid F1 s showed highly restored fertility
(83.4% pollen fertility) relative to diploids F1 s (36.0%). Additional mapping
with Mimulus parishii-M. cardinalis and M. parishii-M. lewisii hybrids
demonstrated that underdominant male sterility is caused by one M. lewisii
specific and one M. cardinalis specific reciprocal translocation, but that
inversions had no direct effects on fertility. We discuss the importance of
translocations as causes of reproductive isolation, and consider models for how
underdominant rearrangements spread and fix despite intrinsic fitness costs.
PMID- 25125145
TI - Transcription activator-like effector nuclease (TALEN)-mediated female-specific
sterility in the silkworm, Bombyx mori.
AB - Engineering sex-specific sterility is critical for developing transgene-based
sterile insect technology. Targeted genome engineering achieved by customized
zinc-finger nuclease, transcription activator-like effector nuclease (TALEN) or
clustered, regularly interspaced, short palindromic repeats/Cas9 systems has been
exploited extensively in a variety of model organisms; however, screening mutated
individuals without a detectable phenotype is still challenging. In addition,
genetically recessive mutations only detectable in homozygotes make the
experiments time-consuming. In the present study, we model a novel genetic system
in the silkworm, Bombyx mori, that results in female-specific sterility by
combining transgenesis with TALEN technologies. This system induces sex-specific
sterility at a high efficiency by targeting the female-specific exon of the B.
mori doublesex (Bmdsx) gene, which has sex-specific splicing isoforms regulating
somatic sexual development. Transgenic animals co-expressing TALEN left and right
arms targeting the female-specific Bmdsx exon resulted in somatic mutations and
female mutants lost fecundity because of lack of egg storage and abnormal
external genitalia. The wild-type sexual dimorphism of abdominal segment was not
evident in mutant females. In contrast, there were no deleterious effects in
mutant male moths. The current somatic TALEN technologies provide a promising
approach for future insect functional genetics, thus providing the basis for the
development of attractive genetic alternatives for insect population management.
PMID- 25125147
TI - Influence of minimally invasive total hip replacement on hip reaction forces and
their orientations.
AB - Minimally invasive surgery (MIS) is becoming increasingly popular. Supporters
claim that the main advantages of MIS total hip replacement (THR) are less pain
and a faster rehabilitation and recovery. Critics claim that safety and efficacy
of MIS are yet to be determined. We focused on a biomechanical comparison between
surgical standard and MIS approaches for THR during the early recovery of
patients. A validated, parameterized musculoskeletal model was set to perform a
squat of a 50th percentile healthy European male. A bilateral motion was chosen
to investigate effects on the contralateral side. Surgical approaches were
simulated by excluding the incised muscles from the computations. Resulting hip
reaction forces and their symmetry and orientation were analyzed. MIS THR seemed
less influential on the symmetry index of hip reaction forces between the
operated and nonoperated leg when compared to the standard lateral approach. Hip
reaction forces at peak loads of the standard transgluteal approach were 24%
higher on the contralateral side when compared to MIS approaches. Our results
suggest that MIS THR contributes to a greater symmetry of hip reaction forces in
absolute value as well as force-orientation following THR.
PMID- 25125148
TI - Enlightened oncologists can provide quality cancer care at reduced costs.
PMID- 25125146
TI - Relevance of the myeloid differentiation factor 88 (MyD88) on RANKL, OPG, and nod
expressions induced by TLR and IL-1R signaling in bone marrow stromal cells.
AB - The myeloid differentiation factor 88 (MyD88) plays a pivotal role in Toll-like
receptor (TLR)- and interleukin-1 receptor (IL-1R)-induced osteoclastogenesis. We
examined the role of MyD88 on p38 mitogen-activated protein kinase (MAPK) and
nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kappaB)
activation and nucleotide-binding oligomerization domain (Nod) induction by
lipopolysaccharide (LPS) and IL-1 beta, and their effect on receptor activator of
NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) production in bone marrow
stromal cell (BMSC). RANKL, Nod1, Nod2, NF-kappaB, and p38 protein levels were
determined by Western blot. Nod2 was stimulated with muramyl dipeptide (MDP)
prior to TLR4 stimulation with LPS. MyD88 deficiency markedly inhibited RANKL
expression after LPS stimulation and increased OPG messenger RNA (mRNA)
production. Also, MyD88 was necessary for NF-kappaB and p38 MAPK activation. MDP
alone did not induce RANKL and OPG expressions; however, when combined with LPS,
their expressions were significantly increased (p < 0.05). Our results support
that MyD88 signaling has a pivotal role in osteoclastogenesis thought NF-kappaB
and p38 activation. Nod2 and especially Nod1 levels were influenced by MyD88.
PMID- 25125149
TI - The variability of ecstasy tablets composition in Brazil.
AB - The content of ecstasy tablets has been changing over the years, and nowadays 3,4
methylenedioxymethamphetamine (MDMA) is not always present in the tablets. The
aim of this study was to investigate the chemical composition in the seized
tablets labeled as ecstasy. We analyzed samples from 150 different seizures made
by Sao Paulo's State Police by gas chromatography-mass spectrometry. MDMA was
present in 44.7% of the analyzed samples, and another twenty different active
substances were identified in these tablets, such as caffeine, 2C-B, piperazines,
amphetamines, phencyclidine, and others. Methamphetamine was present in 22% of
these samples. The results demonstrate a huge shift in the pattern of trafficking
of synthetic drugs, where MDMA has been replaced in tablets mostly by illicit
psychoactive substances, in a clear attempt to bypass the law. The great
variability in the tablets composition may lead to an increased risk of drug
poisoning.
PMID- 25125151
TI - Next-generation therapeutics.
PMID- 25125152
TI - Nepal may have enough doctors but they're in the wrong place.
PMID- 25125150
TI - NDST1 missense mutations in autosomal recessive intellectual disability.
AB - NDST1 was recently proposed as a candidate gene for autosomal recessive
intellectual disability in two families. It encodes a bifunctional GlcNAc N
deacetylase/N-sulfotransferase with important functions in heparan sulfate
biosynthesis. In mice, Ndst1 is crucial for embryonic development and homozygous
null mutations are perinatally lethal. We now report on two additional unrelated
families with homozygous missense NDST1 mutations. All mutations described to
date predict the substitution of conserved amino acids in the sulfotransferase
domain, and mutation modeling predicts drastic alterations in the local protein
conformation. Comparing the four families, we noticed significant overlap in the
clinical features, including both demonstrated and apparent intellectual
disability, muscular hypotonia, epilepsy, and postnatal growth deficiency.
Furthermore, in Drosophila, knockdown of sulfateless, the NDST ortholog, impairs
long-term memory, highlighting its function in cognition. Our data confirm NDST1
mutations as a cause of autosomal recessive intellectual disability with a
distinctive phenotype, and support an important function of NDST1 in human
development.
PMID- 25125154
TI - [The evolution of national health and the development of the nursing practice in
Taiwan].
AB - Nursing is an applied science. While there is a wide range of nursing theories
and nursing care models, resolving the health problems and meeting the health
needs of clients is the common objective of all in the nursing profession. The
nursing profession may be subdivided into hospital clinical nursing and community
health nursing (CHN). CHN is further subdivided into public health nursing,
school health nursing, and industrial health nursing. The past 60 years has been
a period of significant growth and improvement in Taiwan that has enhanced the
nation's socioeconomic condition, general living standards, and general public
health. The nursing profession has seen profound progress as well, not only in
terms of content but also in terms of nursing care models, which are increasingly
framed around core public health needs and take into consideration different
health perspectives. Nursing in Taiwan has gradually established its own
professional function and autonomy.
PMID- 25125155
TI - [The Taiwan Nurses Association and professional diplomacy].
AB - The Taiwan Nurses Association (TWNA) is publishing a special centenary issue to
commemorate the 100th anniversary of the association in 2014. For this issue,
TWNA invited the author to write a review article that addresses the involvement
of the TWNA in professional diplomacy and international exchange over the past
century. The author reviews the history of both TWNA and the International
Council of Nurses and introduces the contributions of the association in the
field of professional diplomacy and the positive contributions of many Taiwan
nursing leaders to global healthcare and society. The purpose of the paper is to
convey the traditions and experiences of TWNA forward to the next generation.
PMID- 25125156
TI - ["Scholar officials": thoughts on the involvement of professional nurses in the
political process].
AB - A growing number of nurses are concerned with / participate in public affairs,
politics, and policymaking processes. In particular, nursing leaders are actively
leveraging their collective power to create interdisciplinary alliances aimed at
encouraging the media and government to confront key nursing issues and implement
healthcare reform. This article highlights the political participation and policy
making process to address the meaning and essence of politics, politics and
nursing, training and strategies of public affairs and political participation,
the shift from academia to health policy, and facilitation of important health
policies. It is hoped that nurses may appropriately use their status and
influence to actively participate in political campaigns and the policymaking
process. By using their professional knowledge and skills, nurses may not only
protect patient safety and public health but also facilitate nursing professional
development and promote the professional image of nursing.
PMID- 25125153
TI - Hypertonic sodium lactate improves fluid balance and hemodynamics in porcine
endotoxic shock.
AB - INTRODUCTION: Based on the potential interest in sodium lactate as an energy
substrate and resuscitative fluid, we investigated the effects of hypertonic
sodium lactate in a porcine endotoxic shock. METHODS: Fifteen anesthetized,
mechanically ventilated pigs were challenged with intravenous infusion of E. coli
endotoxin. Three groups of five animals were randomly assigned to receive 5
mL/kg/h of different fluids: a treatment group received hypertonic sodium lactate
11.2% (HSL group); an isotonic control group receiving 0.9% NaCl (NC group); a
hypertonic control group with the same amount of osmoles and sodium than HSL
group receiving hypertonic sodium bicarbonate 8.4% (HSB group). Hemodynamic and
oxygenation variables, urine output and fluid balance were measured at baseline
and at 30, 60, 120, 210 and 300 min. Skin microvascular blood flow at rest and
during reactive hyperemia was obtained using a laser Doppler flowmetry technique.
Results were given as median with interquartile ranges. RESULTS: Endotoxin
infusion resulted in hypodynamic shock. At 300 min, hemodynamics and oxygenation
were significantly enhanced in HSL group: mean arterial pressure (103 [81-120]
mmHg vs. 49 [41-62] in NC group vs. 71 [60-78] in HSB group), cardiac index (1.6
[1.2-1.8] L/min/m2 vs. 0.9 [0.5-1.1] in NC group vs. 1.3 [0.9-1.6] in HSB group)
and partial pressure of oxygen (366 [308-392] mmHg vs. 166 [130-206] in NC group
vs. 277 [189-303] in HSB group). At the same time, microvascular reactivity was
significantly better in HSL group with a lower venoarterial CO2 tension
difference (5.5 [4-10] mmHg vs. 17 [14-25] in NC group vs. 14 [12-15] in HSB
group). The cumulative fluid balance was lower in HSL group (-325 [-655; -150]
mL) compared to NC (+560 [+230; +900] mL, p = 0.008) and HSB (+185 [-110; +645]
mL, p = 0.03) groups. CONCLUSIONS: In our hypodynamic model of endotoxic shock,
infusion of hypertonic sodium lactate improves hemodynamic and microvascular
reactivity with a negative fluid balance and a better oxygenation.
PMID- 25125157
TI - [Centennial retrospective on the evolution and development of the nursing
practice environment in Taiwan].
AB - The practice environment for nurses has seen tremendous change over the past
century due to the dedication and trailblazing work of nursing pioneers. This
article describes how the nursing practice environment in Taiwan has evolved over
this period. References used include nursing narratives, hospital accreditation
standards, standard operating procedures, workplace safety standards, and
worksite-related values and expectations. The efforts of the professional nursing
community to realize a positive practice environment are further discussed. Over
this century of change, the only thing that has remained unchanged is the
commitment of nurses to "treat patients as one's own family". In the current as
well as the previous periods of manpower shortages in nursing, the nursing
community has managed to turn crisis into opportunity by using the situation to
enhance pay and benefits. Nursing professionalism is widely respected and
recognized throughout Taiwan society. The rapidly changing needs of the 21st
century in aspects such as the advancement of high technology, the rapid growth
of the elderly population, and the fast rate of social change seriously impact
the development of the nursing profession. How to effectively apply high
technology, simplify workflows, provide high quality and humanistic nursing care,
build safe and quality workplaces, attract bright nursing students, and provide
healthcare for the entire population will remain the responsibilities of nursing
for generations to come.
PMID- 25125158
TI - [Centennial retrospective on the evolution and development of nursing research in
Taiwan].
AB - Nursing is a distinct branch of science. Nursing research is not only key to
developing professional knowledge and but also to promoting nursing as an
independent discipline. This paper describes the development and outcomes of
nursing research over the past 100 years and then explores the factors that have
influenced the focus of nursing research in the past. Findings may be applied to
future efforts to promote nursing research. The authors hope that nurses
integrate the best research evidence, the best clinical judgment, and the
expectations of patients in order to provide the best quality of nursing care
through reflection and praxis in nursing research.
PMID- 25125159
TI - [Centennial retrospective on the evolution and development of the nursing
profession in Taiwan].
AB - This article explores the evolution and development of the Taiwanese nursing
profession. After introducing the origins of nursing, this article proceeds to
introduce nursing during various periods in Taiwan, including the early-Qing
Dynasty, foreign missionary nursing, the Japanese Colonial Era, and the
Nationalist Chinese Era following World War Two up to the present. The authors
then present the current situation in the Taiwanese nursing profession in terms
of gender issues, high-technology developments, educational issues, the nursing
licensing examination, hiring and training, multiple role functions, and the
skill-mix care model. Finally, the authors make recommendations for the further
development and improvement of the nursing profession in Taiwan.
PMID- 25125160
TI - [Centennial retrospective on the evolution and development of nursing education
in Taiwan].
AB - Nursing education in Taiwan has developed significantly over the past one hundred
years. Throughout the first half of the 20th century, nursing education in Taiwan
ended at the high school level. However, over the most recent 50 years, this
level has been gradually raised, and nursing doctoral programs are now offered
today. Changes in the nursing profession over the past century have been
influenced by social and political factors, war, the health care policies, and
national education policies. Areas of nursing education that have presented key
challenges to change and innovation include the nursing faculty, curriculum,
teaching materials, and quality of teaching. Today, key future goals for nursing
education in Taiwan are: Raising the entry level of generic nursing education
from junior high to the high-school level, improving the curricula for master's
and doctoral students, cultivating advanced practice nurses, improving the
quality of nursing faculties, and establishing a mechanism to ensure the
consistent quality of nursing education.
PMID- 25125161
TI - [Centennial retrospective on the role expansion of the nursing profession in
Taiwan].
AB - Advanced practice nurses were introduced in Taiwan to address increasingly
complex public healthcare needs, reimbursement reform in the National Health Care
Insurance system, and healthcare organization changes and to ensure high-quality
care for patients. This article discusses the role and the function of nurses;
the expansion and extension of nursing responsibilities; the specific roles of
the advanced practice nurse, the nurse practitioner, the case manager, and the
care manager; the affect of advanced practice on nursing identity and
effectiveness; and key current issues in advanced practice. Suggestions are
provided to improve the professional development of nurses in the future.
PMID- 25125162
TI - [A new vision of nursing: the evolution and development of nursing informatics].
AB - Technology development trends in the 21st century are increasingly focused on the
development of interdisciplinary applications. Advanced information technology
may be applied to integrate nursing care information, simplify nursing processes,
and reduce the time spent on work tasks, thereby increasing the amount of time
that clinical personnel are available to care for patients and ensuring that
patients are provided with high-quality and personalized care services. The
development of nursing information began in Taiwan in 2003 and has since expanded
and thrived. The ability of nursing information to connect formerly insular
national nursing communities promotes the international visibility of Taiwan. The
rapid development of nursing information in Taiwan, resulting in the production
of informative and outstanding results, has received worldwide attention. The
Taiwan Nursing Informatics Association was established in 2006 to nurture nursing
information professionals, develop and apply information technology in the health
care domain, and facilitate international nursing information exchanges. The
association actively promotes nursing information in the areas of administration,
education, research, and clinical practice, thereby integrating nursing with
empirical applications to enhance the service quality and management of nursing
and increase the benefits of nursing teaching and research. To convert
information into knowledge, the association develops individualized strategies
for managing mobile care and employs an interagency network to exchange and
reintegrate resources, establishing active, intelligent nursing based on network
characteristics and an empirical foundation. The mid- and long-term objectives of
the association involve introducing cloud computing and facilitating the
meaningful use of nursing information in both public and government settings,
thereby creating a milestone of developing and expanding nursing information
unique to Taiwan.
PMID- 25125163
TI - [A new vision of nursing: the evolution and development of evidence-based
nursing].
AB - The concept and principles of evidence-based medicine (EBM), first introduced in
1996 in the UK and Canada, have greatly impacted healthcare worldwide. Evidence
based care is a new approach to healthcare that works to reduce the gap between
evidence and practice in order to further the scientific credentials and
practices of the nursing profession. The revolution in healthcare has perhaps
most noticeably impacted the nursing sciences. Today, new methodologies are
increasingly synthesizing knowledge, while expanded access to publication
resources is creating a new era in evidence-based nursing. Therefore, we expect
to see in Taiwan the increased sharing of innovative implementations of evidence
based nursing practice and promotion campaigns and the exploration of a new
evidence-based nursing paradigm for incorporating evidence-based concepts into
the policymaking process, nursing practice, and nursing education. All scientists
in clinical care, education, and research are responsible to establish scientific
nursing knowledge in support of the evidence-based nursing practice.
PMID- 25125164
TI - Metastatic intramucosal colorectal adenocarcinoma: a case to support review of
current concepts (and staging) of early colorectal cancer.
PMID- 25125165
TI - Does early identification of low-grade glioma growth impact outcome?
PMID- 25125166
TI - Special issue: recent advances in muscle research.
PMID- 25125167
TI - Recent advances in muscle research.
PMID- 25125168
TI - Memories of Annemarie Weber.
PMID- 25125170
TI - The formin FHOD1 in cardiomyocytes.
AB - Members of the formin family are known to be involved in the regulation of the
actin cytoskeleton. We have recently identified a muscle specific splice variant
of the formin FHOD3 and demonstrated its role in the maintenance of the
contractile filaments of cardiomyocytes. Here, we characterize the expression and
subcellular localization of FHOD3's closest relative, FHOD1, in the heart.
Confocal microscopy shows that FHOD1 is mainly located at the intercalated disc,
the special type of cell-cell contact between cardiomyocytes, but also partially
associated with the myofibrils. Subcellular targeting of FHOD1 is probably
mediated by its N-terminal domain, since expression constructs lacking this
domain show aberrant localization in primary cultures of neonatal rat
cardiomyocytes. Finally, we show that in contrast to FHOD3, FHOD1 shows increased
expression levels in dilated cardiomyopathy, suggesting that the two formins play
distinct roles and are differentially regulated in cardiomyocytes.
PMID- 25125171
TI - Localization of sarcomeric proteins during myofibril assembly in cultured mouse
primary skeletal myotubes.
AB - It is important to understand how muscle forms normally in order to understand
muscle diseases that result in abnormal muscle formation. Although the structure
of myofibrils is well understood, the process through which the myofibril
components form organized contractile units is not clear. Based on the staining
of muscle proteins in avian embryonic cardiomyocytes, we previously proposed that
myofibrils formation occurred in steps that began with premyofibrils followed by
nascent myofibrils and ending with mature myofibrils. The purpose of this study
was to determine whether the premyofibril model of myofibrillogenesis developed
from studies developed from studies in avian cardiomyocytes was supported by our
current studies of myofibril assembly in mouse skeletal muscle. Emphasis was on
establishing how the key sarcomeric proteins, F-actin, nonmuscle myosin II,
muscle myosin II, and alpha-actinin were organized in the three stages of
myofibril assembly. The results also test previous reports that nonmuscle myosins
II A and B are components of the Z-bands of mature myofibrils, data that are
inconsistent with the premyofibril model. We have also determined that in mouse
muscle cells, telethonin is a late assembling protein that is present only in the
Z-bands of mature myofibrils. This result of using specific telethonin antibodies
supports the approach of using YFP-tagged proteins to determine where and when
these YFP-sarcomeric fusion proteins are localized. The data presented in this
study on cultures of primary mouse skeletal myocytes are consistent with the
premyofibril model of myofibrillogenesis previously proposed for both avian
cardiac and skeletal muscle cells.
PMID- 25125172
TI - Translational control of tropomyosin expression in vertebrate hearts.
AB - The tropomyosin (TM) gene family produces a set of related TM proteins with
important functions in striated and smooth muscle, and nonmuscle cells. In
vertebrate striated muscle, the thin filament consists largely of actin, TM, the
troponin (Tn) complex (Tn-I, Tn-C and Tn-T), and tropomodulin (Tmod) and is
responsible for mediating Ca(2+) control of muscle contraction and relaxation.
There are four known genes (designated as TPM1, TPM2, TPM3, and TPM4) for TM in
vertebrates. The four TM genes generate a multitude of tissue- and developmental
specific isoforms through the use of different promoters, alternative mRNA
splicing, different 3'-end mRNA processing and tissue-specific translational
control. In this review, we have focused mainly on the regulation of TM
expression in striated muscles, primarily in vertebrate hearts with special
emphasis on translational control using mouse and Mexican axolotl animal models.
PMID- 25125169
TI - Regulation of structure and function of sarcomeric actin filaments in striated
muscle of the nematode Caenorhabditis elegans.
AB - The nematode Caenorhabditis elegans has been used as a valuable system to study
structure and function of striated muscle. The body wall muscle of C. elegans is
obliquely striated muscle with highly organized sarcomeric assembly of actin,
myosin, and other accessory proteins. Genetic and molecular biological studies in
C. elegans have identified a number of genes encoding structural and regulatory
components for the muscle contractile apparatuses, and many of them have
counterparts in mammalian cardiac and skeletal muscles or striated muscles in
other invertebrates. Applicability of genetics, cell biology, and biochemistry
has made C. elegans an excellent system to study mechanisms of muscle
contractility and assembly and maintenance of myofibrils. This review focuses on
the regulatory mechanisms of structure and function of actin filaments in the C.
elegans body wall muscle. Sarcomeric actin filaments in C. elegans muscle are
associated with the troponin-tropomyosin system that regulates the actin-myosin
interaction. Proteins that bind to the side and ends of actin filaments support
ordered assembly of thin filaments. Furthermore, regulators of actin dynamics
play important roles in initial assembly, growth, and maintenance of sarcomeres.
The knowledge acquired in C. elegans can serve as bases to understand the basic
mechanisms of muscle structure and function.
PMID- 25125174
TI - A Titan but not necessarily a ruler: assessing the role of titin during thick
filament patterning and assembly.
AB - The sarcomeres of striated muscle are among the most elaborate and dynamic
eukaryotic cellular protein machinery, and the mechanisms by which these
semicrystalline filament networks are initially patterned and assembled remain
contentious. In addition to the acto-myosin filaments that provide motor
function, the sarcomere contains titin filaments, comprised of individual
molecules of the giant Ig- and fibronectin domain-rich protein titin. Titin is
the largest known protein, containing many structurally distinct domains with a
variety of proposed functions, including sarcomere stabilization, the prevention
of over-stretching, and returning to resting length after contraction. One
molecule of titin, which binds to both the Z-disk and the M-line, spans a half
sarcomere, and is proposed to serve as a "molecular ruler" that dictates the
spacing of sarcomeres. The semirigid rod-like A-band region of titin has also
been proposed to act as a scaffold for thick filament formation during muscle
development, but despite decades of research, this hypothesis has not been
rigorously tested. Recent studies in zebrafish have brought into question the
necessity for the A-band region of titin during the early stages of sarcomere
patterning. In this review, we give an overview of the many different roles of
titin in the development and function of striated muscle, and address the
validity of the "molecular ruler" model of myofibrillogenesis in light of the
current literature.
PMID- 25125173
TI - Expression of myotilin during chicken development.
AB - Several missense mutations in the Z-band protein, myotilin, have been implicated
in human muscle diseases such as myofibrillar myopathy, spheroid body myopathy,
and distal myopathy. Recently, we have reported the cloning of chicken myotilin
cDNA. In this study, we have investigated the expression of myotilin in cross
striated muscles from developing chicken by qRT-PCR and in situ hybridizations.
In situ hybridization of embryonic stages shows myotilin gene expression in
heart, somites, neural tissue, eyes and otocysts. RT-PCR and qRT-PCR data,
together with in situ hybridization results point to a biphasic transcriptional
pattern for MYOT gene during early heart development with maximum expression
level in the adult. In skeletal muscle, the expression level starts decreasing
after embryonic day 20 and declines in the adult skeletal muscles. Western blot
assays of myotilin in adult skeletal muscle reveal a decrease in myotilin protein
compared with levels in embryonic skeletal muscle. Our results suggest that MYOT
gene may undergo transcriptional activation and repression that varies between
tissues in developing chicken. We believe this is the first report of the
developmental regulation on myotilin expression in non-mammalian species.
PMID- 25125175
TI - Probing muscle ankyrin-repeat protein (MARP) structure and function.
AB - Muscle ankyrin-repeat proteins (MARPs) have been shown to serve diverse functions
within cardiac and skeletal muscle cells. Apart from their interactions with
sarcomeric proteins like titin or myopalladin that locate them along
myofilaments, MARPs are able to shuttle to the nucleus where they act as
modulators for a variety of transcription factors. The deregulation of MARPs in
many cardiac and skeletal myopathies contributes to their use as biomarkers for
these diseases. Many of their functions are attributed to their domain
composition. MARPs consist of an N-terminal coiled-coil domain responsible for
their dimerization. The C-terminus contains a series of ankyrin repeats, whose
best-characterized function is to bind to the N2A region of the giant sarcomeric
protein titin. Here we investigate the nature of their dimerization and their
interaction with titin more closely. We demonstrate that the coiled-coil domain
in all MARPs enables their homo- and hetero-dimerization in antiparallel fashion.
Protein complementation experiments indicate further antiparallel binding of the
ankyrin repeats to titin's N2A region. Binding of MARP to titin also affects its
PKA mediated phosphorylation. We demonstrate further that MARPs themselves are
phosphorylated by PKA and PKC, potentially altering their structure or function.
These studies elucidate structural relationships within the stretch-responsive
MARP/titin complex in cross-striated muscle cells, and may relate to disease
relevant posttranslational modifications of MARPs and titin that alter muscle
compliance.
PMID- 25125178
TI - SMYD proteins: key regulators in skeletal and cardiac muscle development and
function.
AB - Muscle fibers are composed of myofibrils, one of the most highly ordered
macromolecular assemblies in cells. Recent studies demonstrate that members of
the Smyd family play critical roles in myofibril assembly of skeletal and cardiac
muscle during development. The Smyd family consists of five members including
Smyd1, Smyd2, Smyd3, Smyd4, and Smyd5. They share two highly conserved structural
and functional domains, namely the SET and MYND domains involved in lysine
methylation and protein-protein interaction, respectively. Smyd1 is specifically
expressed in muscle cells under the regulation of myogenic transcriptional
factors of the MyoD and Mef2 families and the serum responsive factor. Loss of
function studies reveal that Smyd1 is required for cardiomyogenesis and sarcomere
assembly in skeletal and cardiac muscles. Smyd2, on another hand, is dispensable
for heart development in mice. However, Smyd2 appears to play a role in
myofilament organization in both skeletal and cardiac muscles via Hsp90
methylation. A Drosophila Smyd4 homologue is a muscle-specific transcriptional
modulator involved in the development or function of adult muscle. The molecular
mechanisms by which Smyd family proteins function in muscle cells are not well
understood. It has been suggested that members of the Smyd family may use
multiple mechanisms to control muscle development and cell differentiation,
including transcriptional regulation, epigenetic regulation via histone
methylation, and methylation of proteins other than histones, such as molecular
chaperone Hsp90.
PMID- 25125176
TI - Protein arginylation, a global biological regulator that targets actin
cytoskeleton and the muscle.
AB - Posttranslational addition of Arg to proteins, mediated by arginyltransferase
ATE1 has been first observed in 1963 and remained poorly understood for decades
since its original discovery. Recent work demonstrated the global nature of
arginylation and its essential role in multiple physiological pathways during
embryogenesis and adulthood and identified over a hundred of proteins arginylated
in vivo. Among these proteins, the prominent role belongs to the actin
cytoskeleton and the muscle, and follow up studies strongly suggests that
arginylation constitutes a novel biological regulator of contractility. This
review presents an overview of the studies of protein arginylation that led to
the discovery of its major role in the muscle.
PMID- 25125180
TI - Structural implications of beta-cardiac myosin heavy chain mutations in human
disease.
AB - Over 500 disease-causing point mutations have been found in the human beta
cardiac myosin heavy chain, many quite recently with modern sequencing
techniques. This review shows that clusters of these mutations occur at critical
points in the sequence and investigates whether the many studies on these mutants
reveal information about the function of this protein.
PMID- 25125177
TI - Getting folded: chaperone proteins in muscle development, maintenance and
disease.
AB - Chaperone proteins are critical for protein folding and stability, and hence are
necessary for normal cellular organization and function. Recent studies have
begun to interrogate the role of this specialized class of proteins in muscle
biology. During development, chaperone-mediated folding of client proteins
enables their integration into nascent functional sarcomeres. In addition to
assisting with muscle differentiation, chaperones play a key role in the
maintenance of muscle tissues. Furthermore, disruption of the chaperone network
can result in neuromuscular disease. In this review, we discuss how chaperones
are involved in myofibrillogenesis, sarcomere maintenance, and muscle disorders.
We also consider the possibilities of therapeutically targeting chaperones to
treat muscle disease.
PMID- 25125179
TI - Cell biology of sarcomeric protein engineering: disease modeling and therapeutic
potential.
AB - The cardiac sarcomere is the functional unit for myocyte contraction. Ordered
arrays of sarcomeric proteins, held in stoichiometric balance with each other,
respond to calcium to coordinate contraction and relaxation of the heart. Altered
sarcomeric structure-function underlies the primary basis of disease in multiple
acquired and inherited heart disease states. Hypertrophic and restrictive
cardiomyopathies are caused by inherited mutations in sarcomeric genes and result
in altered contractility. Ischemia-mediated acidosis directly alters sarcomere
function resulting in decreased contractility. In this review, we highlight the
use of acute genetic engineering of adult cardiac myocytes through stoichiometric
replacement of sarcomeric proteins in these disease states with particular focus
on cardiac troponin I. Stoichiometric replacement of disease causing mutations
has been instrumental in defining the molecular mechanisms of hypertrophic and
restrictive cardiomyopathy in a cellular context. In addition, taking advantage
of stoichiometric replacement through gene therapy is discussed, highlighting the
ischemia-resistant histidine-button, A164H cTnI. Stoichiometric replacement of
sarcomeric proteins offers a potential gene therapy avenue to replace mutant
proteins, alter sarcomeric responses to pathophysiologic insults, or neutralize
altered sarcomeric function in disease.
PMID- 25125183
TI - Myosin VI localization and expression in striated muscle pathology.
AB - Myosin VI (MVI) is a unique unconventional myosin translocating, unlike other
myosins, towards the minus end of actin filaments. It is involved in numerous
cellular processes such as endocytosis, intracellular trafficking, cell
migration, and transcription. In mammalian skeletal muscles it localizes mainly
to sarcoplasmic reticulum and is also present within the muscle nuclei and at the
neuromuscular junction (Karolczak et al. Histochem Cell Biol 2013; 23:219-228).
We have also shown that in denervated rat hindlimb muscle the MVI expression
level is significantly increased and its localization is changed, indicating an
important role of MVI in striated muscle pathology. Here, we addressed this
problem by examining the distribution and expression levels of myosin VI in
biopsies of skeletal muscles from patients with different myopathies. We found
that, particularly in myopathies associated with fiber atrophy, the amount of MVI
was enhanced and its localization in affected fibers was changed. Also, since a
mutation within the human MVI gene was shown to be associated with
cardiomyopathy, we assessed MVI localization and expression level in cardiac
muscle using wild type and MLP(-/-) mice, a dilated cardiomyopathy model. No
significant difference in MVI expression level was observed for both types of
animals. MVI was found at intercalated discs and also at the sarcoplasmic
reticulum. In the knockout mice, it was also present in ring-like structures
surrounding the nuclei. The data indicate that in striated muscle MVI could be
engaged in sarcoplasmic reticulum maintenance and/or functioning, vesicular
transport, signal transmission and possibly in gene transcription.
PMID- 25125184
TI - The pathway for force transmission in the rat anococcygeus muscle: a tale of two
tendons.
AB - Smooth muscles forming the wall of tissues having conduit and reservoir functions
(including blood vessels, intestinal tract, and stomach, gall bladder, urinary
bladder, respectively) are organized into sheets or layers. The pathway for force
transmission emanates from myosin interaction with actin filaments attached to
intracellular dense bodies linked by the cytoskeleton to plasma membrane dense
bodies which are adhesion sites for the extracellular matrix. The extracellular
matrix is continuous throughout and between muscle layers, facilitating their
coordinated function. There are a few instances where smooth muscles are
organized in small longitudinal bundles with elastic tendinous ends, such as the
pilomotor muscles of skin, the ciliary muscle of the eye, and costo-uterine
muscle. In this study, we examine ultrastructure of two tendons that tether the
anococcygeus muscle of the rat from the spine to the colon, the former a true
tendon (myotendinous junction) and the latter a layer of connective tissue
(intramuscular tendon). These regions show morphological specializations in the
distribution and thickness of dense bodies, basement membrane, fiber shape and
quantity of extracellular matrix. At the plasma membrane between dense bodies are
caveolae, flask shaped structures primarily responsible for signal transduction,
proliferation and electromechanical coupling. Changes also occur in caveolar
regions, where the basement membrane is thickened and attachments to
extracellular matrix are seen. Together, both regions of the plasma membrane are
designed to facilitate force transmission.
PMID- 25125181
TI - Understanding cardiac sarcomere assembly with zebrafish genetics.
AB - Mutations in sarcomere genes have been found in many inheritable human diseases,
including hypertrophic cardiomyopathy. Elucidating the molecular mechanisms of
sarcomere assembly shall facilitate understanding of the pathogenesis of
sarcomere-based cardiac disease. Recently, biochemical and genomic studies have
identified many new genes encoding proteins that localize to the sarcomere.
However, their precise functions in sarcomere assembly and sarcomere-based
cardiac disease are unknown. Here, we review zebrafish as an emerging vertebrate
model for these studies. We summarize the techniques offered by this animal model
to manipulate genes of interest, annotate gene expression, and describe the
resulting phenotypes. We survey the sarcomere genes that have been investigated
in zebrafish and discuss the potential of applying this in vivo model for larger
scale genetic studies.
PMID- 25125186
TI - Tenascin-C in development and disease of blood vessels.
AB - Tenascin-C (TNC) is an extracellular glycoprotein categorized as a matricellular
protein. It is highly expressed during embryonic development, wound healing,
inflammation, and cancer invasion, and has a wide range of effects on cell
response in tissue morphogenesis and remodeling including the cardiovascular
system. In the heart, TNC is sparsely detected in normal adults but transiently
expressed at restricted sites during embryonic development and in response to
injury, playing an important role in myocardial remodeling. Although TNC in the
vascular system appears more complex than in the heart, the expression of TNC in
normal adult blood vessels is generally low. During embryonic development,
vascular smooth muscle cells highly express TNC on maturation of the vascular
wall, which is controlled in a way that depends on the embryonic site of cell
origin. Strong expression of TNC is also linked with several pathological
conditions such as cerebral vasospasm, intimal hyperplasia, pulmonary artery
hypertension, and aortic aneurysm/ dissection. TNC synthesized by smooth muscle
cells in response to developmental and environmental cues regulates cell
responses such as proliferation, migration, differentiation, and survival in an
autocrine/paracrine fashion and in a context-dependent manner. Thus, TNC can be a
key molecule in controlling cellular activity in adaptation during normal
vascular development as well as tissue remodeling in pathological conditions.
PMID- 25125182
TI - Finding the sweet spot: assembly and glycosylation of the dystrophin-associated
glycoprotein complex.
AB - The dystrophin-associated glycoprotein complex (DGC) is a collection of
glycoproteins that are essential for the normal function of striated muscle and
many other tissues. Recent genetic studies have implicated the components of this
complex in over a dozen forms of muscular dystrophy. Furthermore, disruption of
the DGC has been implicated in many forms of acquired disease. This review aims
to summarize the current state of knowledge regarding the processing and assembly
of dystrophin-associated proteins with a focus primarily on the dystroglycan
heterodimer and the sarcoglycan complex. These proteins form the transmembrane
portion of the DGC and undergo a complex multi-step processing with proteolytic
cleavage, differential assembly, and both N- and O-glycosylation. The enzymes
responsible for this processing and a model describing the sequence and
subcellular localization of these events are discussed.
PMID- 25125185
TI - Smooth muscle-protein translocation and tissue function.
AB - Smooth muscle (SM) tissue is a complex organization of multiple cell types and is
regulated by numerous signaling molecules (neurotransmitters, hormones,
cytokines, etc.). SM contractile function can be regulated via expression and
distribution of the contractile and cytoskeletal proteins, and activation of any
of the second messenger pathways that regulate them. Spatial-temporal changes in
the contractile, cytoskeletal or regulatory components of SM cells (SMCs) have
been proposed to alter SM contractile activity. Ca(2+)
sensitization/desensitization can occur as a result of changes at any of these
levels, and specific pathways have been identified at all of these levels.
Understanding when and how proteins can translocate within the cytoplasm, or to
and-from the plasmalemma and the cytoplasm to alter contractile activity is
critical. Numerous studies have reported translocation of proteins associated
with the adherens junction and G protein-coupled receptor activation pathways in
isolated SMC systems. Specific examples of translocation of vinculin to and from
the adherens junction and protein kinase C (PKC) and 17 kDa PKC-potentiated
inhibitor of myosin light chain phosphatase (CPI-17) to and from the plasmalemma
in isolated SMC systems but not in intact SM tissues are discussed. Using both
isolated SMC systems and SM tissues in parallel to pursue these studies will
advance our understanding of both the role and mechanism of these pathways as
well as their possible significance for Ca(2+) sensitization in intact SM tissues
and organ systems.
PMID- 25125188
TI - Is sarcomere lattice geometry optimal? Analysis of several potential virtual
polygon cross-sectional patterns for actin and myosin myofilaments in muscle.
AB - The hexagonal arrangement of actin filaments in skeletal muscle is not the
fundamental geometrical or functioning myofilament unit. This analysis of several
possible sarcomere lattice geometries for the arrangement of the actin and myosin
filaments identifies several geometrical constraints that can be compared for
their effect on muscle sarcomere functioning and efficiency. Three distinct
virtual polygons, with myosins at their vertices and that tessellate the plane,
are compared for both centered actin and perimeter actin arrangements. The
analysis evaluates the optimal ratio of myosin to actin filaments, the packing
density, and the effect on new myofilament formation in muscle hypertrophy for
the various lattice geometries. The results support the view that no single
measure of geometrical effectiveness can evaluate definitively the efficiency of
any particular arrangement of the myofilaments. The analysis provides
quantitative measures of several parameters that, taken overall, support the
effectiveness of the myofilament arrangement in Nature. It provides a new
definition of the fundamental myofilament unit (FMU). It is possible to calculate
the number of actin and myosin myofilaments that need to be added to each polygon
arrangement of the myofilaments to create a new FMU for that specific geometry.
This leads to useful conclusions about the biochemical efficiency involved in
where such units arise in the course of muscle hypertrophy. It supports the idea
that the evolutionary endpoint for optimizing muscle's force-generating function
can be better understood via the concepts of a FMU and the polygon arrangement of
the sarcomere lattice geometry.
PMID- 25125189
TI - Myosin VIIA is a marker for the cone accessory outer segment in zebrafish.
AB - The accessory outer segment, a cytoplasmic structure running alongside the
photoreceptor outer segment, has been described in teleost fishes, excluding the
model organism zebrafish. So far, the function of the accessory outer segment is
unknown. Here, we describe the ultrastructure of the zebrafish cone accessory
outer segment by electron microscopy. Starting at the connecting cilium, the
accessory outer segment runs parallel alongside the cone outer segment (COS). A
thin plasma bridge connects the outer segment with the accessory outer segment,
whose surface is enlarged by foldings and invaginations. Beside the morphological
descriptions, we demonstrate that the Usher protein myosin VIIa (Myo7a) is a
specific marker for the zebrafish cone accessory outer segment. Zebrafish cone
photoreceptors possess a large and well-differentiated accessory outer segment,
in which the unconventional motor protein Myo7a is highly enriched. The direct
cytoplasmic contact with the COS as well as the surface enlargement of the
accessory outer segment suggests an important role of this structure in transport
and exchange of metabolites between the COS and the surrounding retinal pigment
epithelium. In future studies of the outer retina, more attention should be paid
to this often neglected structure.
PMID- 25125191
TI - Pre-clinical research in small animals using radiotherapy technology--a
bidirectional translational approach.
AB - For translational cancer research, pre-clinical in-vivo studies using small
animals have become indispensable in bridging the gap between in-vitro cell
experiments and clinical implementation. When setting up such small animal
experiments, various biological, technical and methodical aspects have to be
considered. In this work we present a comprehensive topical review based on
relevant publications on irradiation techniques used for pre-clinical cancer
research in mice and rats. Clinical radiotherapy treatment devices for the
application of external beam radiotherapy and brachytherapy as well as dedicated
research irradiation devices are feasible for small animal irradiation depending
on the animal model and the experimental goals. In this work, appropriate
solutions for the technological transfer of human radiation oncology to small
animal radiation research are summarised. Additionally, important information
concerning the experimental design is provided such that reliable and clinically
relevant results can be attained.
PMID- 25125187
TI - The role of mechanotransduction on vascular smooth muscle myocytes' [corrected]
cytoskeleton and contractile function.
AB - Smooth muscle (SM) exhibits a highly organized structural hierarchy that extends
over multiple spatial scales to perform a wide range of functions at the
cellular, tissue, and organ levels. Early efforts primarily focused on
understanding vascular SM (VSM) function through biochemical signaling. However,
accumulating evidence suggests that mechanotransduction, the process through
which cells convert mechanical stimuli into biochemical cues, is requisite for
regulating contractility. Cytoskeletal proteins that comprise the extracellular,
intercellular, and intracellular domains are mechanosensitive and can remodel
their structure and function in response to external mechanical cues.
Pathological stimuli such as malignant hypertension can act through the same
mechanotransductive pathways to induce maladaptive remodeling, leading to changes
in cellular shape and loss of contractile function. In both health and disease,
the cytoskeletal architecture integrates the mechanical stimuli and mediates
structural and functional remodeling in the VSM.
PMID- 25125192
TI - Improving perfusion quantification in arterial spin labeling for delayed arrival
times by using optimized acquisition schemes.
AB - OBJECTIVE: The improvement in Arterial Spin Labeling (ASL) perfusion
quantification, especially for delayed bolus arrival times (BAT), with an
acquisition redistribution scheme mitigating the T1 decay of the label in multi
TI ASL measurements is investigated. A multi inflow time (TI) 3D-GRASE sequence
is presented which adapts the distribution of acquisitions accordingly, by
keeping the scan time constant. MATERIAL AND METHODS: The MR sequence increases
the number of averages at long TIs and decreases their number at short TIs and
thus compensating the T1 decay of the label. The improvement of perfusion
quantification is evaluated in simulations as well as in-vivo in healthy
volunteers and patients with prolonged BATs due to age or steno-occlusive
disease. RESULTS: The improvement in perfusion quantification depends on BAT. At
healthy BATs the differences are small, but become larger for longer BATs
typically found in certain diseases. The relative error of perfusion is improved
up to 30% at BATs>1500ms in comparison to the standard acquisition scheme.
CONCLUSION: This adapted acquisition scheme improves the perfusion measurement in
comparison to standard multi-TI ASL implementations. It provides relevant benefit
in clinical conditions that cause prolonged BATs and is therefore of high
clinical relevance for neuroimaging of steno-occlusive diseases.
PMID- 25125193
TI - Bacteria-mediated aerobic degradation of hexacosane in vitro conditions.
AB - In vitro degradation of hexacosane (C26H54), a HMW n-alkane, was studied in MSM
by two bacterial strains i.e., Pseudomonas sp. BP10 and Stenotrophomonas
nitritireducens E9, isolated from petroleum sludge, in isolation and combination.
The results revealed that both the strains were able to metabolize hexacosane by
82% in isolation and 98% in their consortium after 7days. An enhancement of 16%
in hexacosane degradation by the consortium indicated an additive action of
bacterial strains. However, in control, a degradation of 21% was attributed to
abiotic factors. During incubation with hexacosane, both the bacteria continued
to multiply in isolation and consortium, which reflected that hexacosane was
utilized by bacteria as a carbon and energy source. Activities of alkane
hydroxylase and alcohol dehydrogenase were differentially expressed in isolation
and combination, indicating their involvement in hexacosane degradation. Enhanced
cell surface hydrophobicity and emulsification index and reduced surface tension
also supported the degradation process.
PMID- 25125194
TI - Biodiesel from wet microalgae: extraction with hexane after the microwave
assisted transesterification of lipids.
AB - A chloroform-free novel process for the efficient production of biodiesel from
wet microalgae is proposed. Crude biodiesel is produced through extraction with
hexane after microwave-assisted transesterification (EHMT) of lipids in wet
microalgae. Effects of different parameters, including reaction temperature,
reaction time, methanol dosage, and catalyst dosage, on fatty acids methyl esters
(FAMEs) yield are investigated. The yield of FAME extracted into the hexane from
the wet microalgae is increased 6-fold after the transesterification of lipids.
The yield of FAME obtained through EHMT of lipids in wet microalgae is comparable
to that obtained through direct transesterification of dried microalgae biomass
with chloroform; however, FAME content in crude biodiesel obtained through EHMT
is 86.74%, while that in crude biodiesel obtained through the chloroform-based
process is 75.93%. EHMT ensures that polar pigments present in microalgae are not
extracted into crude biodiesel, which leads to a 50% reduction in nitrogen
content in crude biodiesel.
PMID- 25125195
TI - Characterization of corncob-derived biochar and pyrolysis kinetics in comparison
with corn stalk and sawdust.
AB - In this study, thermal and physicochemical characterization results of corncob
(CC) and its derived biochars were analyzed and differentiated from sawdust (SD)
and cornstalk (CS). The pyrolysis temperature shows the largest effect on the
yield of biochar produced compare with residing time, heating rate, and feedstock
particle size. The CC-derived biochars produced at temperatures ranging from 300
to 600 degrees C were analyzed. The CC was thermochemically altered to a stable
biochar when the pyrolysis temperature was set to over 500 degrees C. To deduce
the reaction mechanism of the CC during the major thermal decomposition stage, 16
mechanisms in solid-state reactions were applied. The reaction order and
nucleation mechanisms described the thermal decomposition of the CC. By using the
best-fitted mechanisms, the kinetic parameters were calculated. The weight active
energy of the CC was 122.42kJ/mol, which was the lowest value compared to those
of CS and SD.
PMID- 25125196
TI - Biocapture of CO2 from biogas by oleaginous microalgae for improving methane
content and simultaneously producing lipid.
AB - This study aimed to use oleaginous microalgae to capture CO2 from biogas for
improving methane content and simultaneously producing lipid. Several microalgae
were screened for their ability to grow and produce lipid using CO2 in biogas. A
marine Chlorella sp. was the most suitable strain for capturing CO2 and producing
lipid using biogas (50% v/v CO2 in methane) as well as using 50% v/v CO2 in air.
The medium and operating conditions were optimized through response surface
methodology (RSM). The optimal concentrations of KNO3 and K2HPO4 were 0.80gL(-1)
and 0.06gL(-1), respectively. The optimal operating conditions were: initial pH
of 7.8, initial cell concentration of 10(7.5)cellsmL(-1), light intensity of
4500lux and gas flow rate of 0.03Lmin(-1). After optimization, 89.3% of CO2 was
removed from biogas and the methane content was increased up to 94.7%. The lipid
productivity was 94.7mgL(-1)day(-1).
PMID- 25125197
TI - Application of hydrothermal treatment to affect the fermentability of Pinus
radiata pulp mill effluent sludge.
AB - A hybrid technique incorporating a wet oxidation stage and secondary fermentation
step was used to process Pinus radiata pulp mill effluent sludge. The effect of
hydrothermal oxidation at high temperature and pressure on the hydrolysis of
constituents of the waste stream was studied. Biochemical acidogenic potential
assays were conducted to assess acid production resulting from anaerobic
hydrolysis of the wet oxidised hydrolysate under acidogenic conditions.
Significant degradation of the lignin, hemicellulose, suspended solids,
carbohydrates and extractives were observed with wet oxidation. In contrast,
cellulose showed resistance to degradation under the experimental conditions.
Extensive degradation of biologically inhibitory compounds by wet oxidation did
not show a beneficial impact on the acidogenic or methanogenic potential compared
to untreated samples.
PMID- 25125198
TI - High cell density lipid rich cultivation of a novel microalgal isolate Chlorella
sorokiniana FC6 IITG in a single-stage fed-batch mode under mixotrophic
condition.
AB - A single-stage mixotrophic cultivation strategy was developed with a novel
microalgal isolate Chlorella sorokiniana FC6 IITG for high cell density lipid
rich biomass generation. The strain was evaluated for growth and lipid content
under different physico-chemical parameters, nutritional conditions and trophic
modes. Finally, a single-stage mixotrophic fed-batch cultivation strategy was
demonstrated with intermittent feeding of key nutrients along with dynamic
increase in light intensity for high cell density biomass and sodium acetate as
elicitor for lipid enrichment. The key findings: (i) glucose and sodium acetate
was identified as growth supporting and lipid inducing nutrients, respectively;
(ii) mixotrophic batch cultivation resulted in maximum biomass and lipid
productivity (mgL(-1)day(-1)) of 455.5 and 111.85, respectively; (iii) single
stage mixotrophic fed-batch cultivation showed maximum biomass productivity of
1.93gL(-1)day(-1) (biomass titer 15.81gL(-1)) and lipid productivity of 550mgL(
1)day(-1); (iv) biodiesel properties were in accordance with international
standards.
PMID- 25125199
TI - Brait-Fahn-Schwarz disease: the missing link between ALS and Parkinson's disease.
PMID- 25125200
TI - Topographic determinants of mobile vertebrate predator hotspots: current
knowledge and future directions.
AB - Despite being identified as a driver of mobile predator aggregations (hotspots)
in both marine and terrestrial environments, topographic complexity has long
remained a challenging concept for scientists to visualise and a difficult
parameter to estimate. It is only with the advent of high-speed computers and the
recent popularisation of geographical information systems (GIS) that terrain
attributes have begun to be quantitatively measured in three-dimensional space
and related to wildlife dynamics, making the well-established field of
geomorphometry (or 'digital terrain modelling') a discipline of growing appeal to
biologists. Although a diverse array of numerical metrics is now available to
describe the shape, geometry and physical properties of natural habitats, few of
these are known to, or adequately used by, ecologists. In this review, we examine
the nature and usage of 56 geomorphometrics extracted from the ecological
modelling literature over a period of 32 years (1979-2011). We show that, in
studies of mobile predators, numerous topographic variables have largely been
overlooked in favour of single basic metrics that do not, on their own, fully
capture the complexity of continuous landscapes. Based on a simulation approach,
we assess the redundancy and correlation structure of these metrics and
demonstrate that a majority are highly collinear. We highlight a suite of 7-8
complementary metrics which best explain topographic patterns across a
bathymetric grid of the west Australian seafloor, and contend that field and
analytical protocols should prioritise variables of these types, particularly
when the responses of predator populations to physical habitat features are of
interest. We suggest that prominent structures such as canyons, seamounts or
mountain chains can serve as useful proxies for predator hotspots, especially in
remote locations where access to high-resolution biological data is often
limited.
PMID- 25125201
TI - Minimally invasive surgical instruments with an accessory channel capable of
integrating fibre-optic cable for optical biopsy: a review of the state of the
art.
AB - This review article provides a comprehensive overview and classification of
minimally invasive surgical instruments with an accessory channel incorporating
fibreoptics or another auxiliary device for various purposes. More specifically,
this review was performed with the focus on the newly emerging field of optical
biopsy, its objective being to discuss primarily the instruments capable of
carrying out the optical biopsy and subsequent tissue resection. Instruments
housing the fibreoptics for other uses, as well as instruments with an accessory
channel capable of housing the fibreoptics instead of their original auxiliary
device after relevant design modifications, supplement the review. The entire
Espacenet and Scopus databases were searched, yielding numerous patents and
articles on conceptual and existing instruments satisfying the criteria. The
instruments were categorised based on the function the fibreoptics or the
auxiliary device serves. On the basis of their geometrical placement with respect
to the tissue resector or manipulator, the subcategories were further defined.
This subdivision was used to identify the feasibility of performing the optical
biopsy and the tissue resection in an accurate and successive fashion. In
general, the existing concepts or instruments are regarded as limited with regard
to such a functionality, either due to the placement of their accessory channel
with or without the fibreoptics or due to the operational restrictions of their
tissue manipulators. A novel opto-mechanical biopsy harvester, currently under
development at Delft University of Technology, is suggested as a promising
alternative, ensuring a fast and accurate succession of the optical and the
mechanical biopsies of a flat superficial tissue.
PMID- 25125203
TI - Computational study of van der Waals complexes between borylenes and
hydrocarbons.
AB - The addition of borylenes (RB) to prototypical carbon-carbon multiple bonds
(ethyne, ethene) and the insertion into a C-H bond of methane involves weakly
bound van der Waals complexes of the reaction partners according to computational
chemistry methods. Geometries of all complexes were optimized using spin
component scaled second-order Moller-Plesset perturbation theory (SCS-MP2) in
combination with a quadruple-zeta (def2-QZVP) basis set. Energies were further
refined using the coupled-cluster (CCSD(T)) method in combination with basis sets
up to quadruple-zeta quality (def2-QZVP and aug-cc-pVTZ). All of the complexes of
borylenes studied correspond to shallow minima on their potential-energy
surfaces. Borylene complexes with ethyne are the most stable and those with
methane are the least stable ones. Aminoborylene complexes BNHR with ethyne and
ethene are stabilized mainly by NH???pi interactions. Symmetry-adapted
perturbation theory (SAPT) was performed to analyze the nature of the interaction
between borylene molecules and hydrocarbons. Most of the ethyne complexes are
dominated by electrostatic interactions, whereas for most of the ethene and all
of the methane complexes the interaction is mainly dispersive.
PMID- 25125202
TI - Peptide receptor chemoradionuclide therapy in small cell carcinoma: from bench to
bedside.
AB - PURPOSE: Small cell cancers (SmCC), whether pulmonary (SCLC) or extrapulmonary,
have a poor prognosis unless localised at diagnosis. Given a proportion of these
cancers express somatostatin receptor subtype 2 (SSTR2), we aimed to investigate
the efficacy of targeted peptide receptor chemoradionuclide therapy (PRCRT).
METHODS: In this preclinical study, we used a SCLC xenograft mouse model with
high expression of SSTR2 to investigate the effect of peptide receptor
radionuclide therapy (PRRT) with chemotherapy compared to either alone. We
subsequently explored the clinical utility in a patient with SmCC with high SSTR
expression treated with PRCRT. RESULTS: Robust expression of SSTR2 in NCI-H69
SCLC xenografts was documented by (68)Ga-DOTA-octreotate (GaTate) (tumour to
background uptake ratio = 35). The combination of PRRT using (177)Lu-DOTA
octreotate (LuTate) with carboplatin/etoposide (C/E) chemotherapy was more
effective than either LuTate or C/E alone for regression of the NCI-H69 model (p
value < 0.05). PRCRT was associated with significantly prolonged survival versus
PRRT (p value = 0.0001) or chemotherapy alone (p value = 0.0058). In the
subsequent case study, a patient with relapsed SmCC with high SSTR2 expression on
GaTate PET underwent PRCRT with radiosensitising etoposide with evidence of a
complete metabolic response for 4 months. CONCLUSION: Given the limited treatment
options in this setting, PRCRT is a promising therapeutic option for SSTR2
expressing SmCC.
PMID- 25125204
TI - Rationally synthesized five-fold twinned core-shell Pt3Ni@Rh nanopentagons,
nanostars and nanopaddlewheels for selective reduction of a phenyl ring of
phthalimide.
AB - Surface-energy fine-tuned five-fold twinned nanostructures with a core-shell
Pt3Ni@Rh structural motif, namely, a core-shell Pt3Ni@Rh pentagon, a core-shell
Pt3Ni@Rh starfish, and a paddlewheel with a Pt3Ni crankshaft and two Rh five-fold
starfish wheels, are prepared by rationally designed stepwise heteroepitaxial
growth. Unusual selective hydrogenation of the phenyl ring in phthalimide is
accomplished with moderately active core-shell Pt3Ni@Rh pentagons and starfish
like nanoparticles. The most active paddlewheel structure proceeds to further
reduce one carbonyl group, indicating the sequential nature of phthalimide
reduction by Rh nanoparticle catalysis.
PMID- 25125205
TI - Hypothermia and operative mortality during on-pump coronary artery bypass
grafting.
AB - OBJECTIVE: Controversy surrounds the effect of hypothermia on operative mortality
during cardiac surgery. The present study accessed a large clinical database of
coronary artery bypass graft operations to address the issue. METHODS: A
retrospective review of the Society of Thoracic Surgeons Adult Cardiac Surgery
Database identified patients treated with isolated, nonemergency, on-pump
coronary artery bypass grafting from July 2011 to December 2012. The patients
were divided into 3 groups according to their lowest core temperature during the
procedure: moderate hypothermia (<= 34 degrees C), mild hypothermia (>34
degrees C but <= 36 degrees C), and normothermia (>36 degrees C). The primary
endpoint of the study was operative mortality, defined according to the Database
criteria. RESULTS: During the study period, 142,541 patients were available for
analysis; 94,777 (66.5%) received moderate hypothermia, 42,750 (30.3%) mild
hypothermia, and 5014 (3.5%) normothermia. Operative mortality occurred in 1394
patients (1.5%) in the moderate hypothermia, 534 (1.3%) in the mild hypothermia,
and 105 (2.1%) in the normothermia group. Multivariate analysis identified
hypothermia (both mild [odds ratio, 0.66; 95% confidence interval, 0.54-0.81; P <
.0001] and moderate [odds ratio, 0.73; 95% confidence interval, 0.60-0.89; P =
.0015]) was protective against operative mortality compared with normothermia. No
incremental benefit was noted between the different hypothermia grades (P =
.0827). CONCLUSIONS: Most patients receive hypothermia during on-pump coronary
artery bypass grafting. Hypothermia is protective against operative mortality
compared with normothermia in such patients. Moderate hypothermia does not
provide additional survival benefit.
PMID- 25125208
TI - Successful aortic valve repair after trauma-induced aortic regurgitation.
PMID- 25125207
TI - Pilot study of pulmonary arterial branch sealing using energy devices in an ex
vivo model.
AB - OBJECTIVE: Vascular endostaplers are bulky and can be dangerous when dividing
small pulmonary arterial (PA) branch vessels during video-assisted thoracoscopic
lobectomy. We aimed to evaluate and compare the immediate efficacy of modern
energy sealing devices in an ex vivo PA sealing model. METHODS: Patients
undergoing anatomical lung resection or lung transplantation were recruited for a
prospective cohort pilot study. Four devices were evaluated: Harmonic Ace
(Ethicon, Cincinnati, Ohio), Thunderbeat (Olympus, Tokyo, Japan), LigaSure
(Covidien, Boulder, Colo), and Enseal (Ethicon; Cincinnati, Ohio). After
anatomical lung resection, the PA branches were dissected in vitro. Sealing was
then performed with 1 of the sealing devices, the vessel was slowly pressurized,
and the bursting pressure was recorded. RESULTS: Forty-nine PA branches were
sealed in 14 patients. The mean PA branch diameter was 7.4 mm (1.8-14.5 mm). Ten
patients had normal PA pressure and 3 had PA hypertension. The mean bursting
pressure in each was as follows: Harmonic Ace group, 415.5 mm Hg (137.1-1388.4 mm
Hg), Thunderbeat group, 875 mm Hg (237.1-2871.3 mm Hg); LigaSure group, 214.7 mm
Hg (0-579.6 mm Hg); Enseal group, 133.7 mm Hg (0-315.38 mm Hg). There were 2
complete sealing failures: LigaSure (diameter 6.78 mm) and Enseal (diameter 8.3
mm). CONCLUSIONS: In this pilot study to examine energy sealing of PA branches in
a simulated ex vivo model, vascular sealing using energy was effective and was
able to sustain high intraluminal bursting pressures. Further research is needed
to determine the in vivo and long-term safety of PA branch energy sealing.
PMID- 25125206
TI - Contemporary outcomes of complete atrioventricular septal defect repair: analysis
of the Society of Thoracic Surgeons Congenital Heart Surgery Database.
AB - OBJECTIVE: Contemporary outcomes data for complete atrioventricular septal defect
(CAVSD) repair are limited. We sought to describe early outcomes of CAVSD repair
across a large multicenter cohort, and explore potential associations with
patient characteristics, including age, weight, and genetic syndromes. METHODS:
Patients in the Society of Thoracic Surgeons Congenital Heart Surgery Database
having repair of CAVSD (2008-2011) were included. Preoperative, operative, and
outcomes data were described. Univariate associations between patient factors and
outcomes were described. RESULTS: Of 2399 patients (101 centers), 78.4% had Down
syndrome. Median age at surgery was 4.6 months (interquartile range, 3.5-6.1
months), with 11.8% (n = 284) aged <= 2.5 months. Median weight at surgery was
5.0 kg (interquartile range, 4.3-5.8 kg) with 6.3% (n = 151) < 3.5 kg. Pulmonary
artery band removal at CAVSD repair was performed in 122 patients (4.6%). Major
complications occurred in 9.8%, including permanent pacemaker implantation in
2.7%. Median postoperative length of stay (PLOS) was 8 days (interquartile range,
5-14 days). Overall hospital mortality was 3.0%. Weight < 3.5 kg and age <= 2.5
months were associated with higher mortality, longer PLOS, and increased
frequency of major complications. Patients with Down syndrome had lower rates of
mortality and morbidities than other patients; PLOS was similar. CONCLUSIONS: In
a contemporary multicenter cohort, most patients with CAVSD have repair early in
the first year of life. Prior pulmonary artery band is rare. Hospital mortality
is generally low, although patients at extremes of low weight and younger age
have worse outcomes. Mortality and major complication rates are lower in patients
with Down syndrome.
PMID- 25125209
TI - Results of type II hybrid arch repair with zone 0 stent graft deployment for
complex aortic arch pathology.
AB - OBJECTIVE: To review the early results of a less invasive, single-stage hybrid
arch procedure involving replacement of the ascending aorta, arch debranching,
and zone 0 antegrade stent graft deployment. METHODS: Between May 2007 and
January 2012, 20 patients with both acute and chronic aortic pathology were
managed at 2 institutions with a type 2 hybrid arch procedure. Indications
included diffuse atherosclerotic aneurysm, false lumen expansion of chronic
aortic dissections, penetrating atherosclerotic ulcer, and acute type A
dissection. Mean age was 67 +/- 16.8 years with a mean European System for
Cardiac Operative Risk Evaluation II score of 29.5 +/- 19.4. Postoperative
clinical and imaging follow-up was complete to a mean 18.5 +/- 15.3 months.
RESULTS: Successful zone 0 stent graft deployment was achieved in all cases.
There was 1 in-hospital mortality (5%). A second death occurred at 40 days
postoperation. Other complications included a permanent neurologic deficit in 1
patient (5%), transient paraplegia in 4 patients (20%), and 3 patients had
respiratory complications (15%). There were no cases of renal failure requiring
dialysis. Stent-related complications were identified in 4 patients (20%),
including 3 type I endoleaks, none of which were at zone 0. There was 1 type II
endoleak and a case of stent infolding. Two patients required a second successful
endografting procedure. CONCLUSIONS: This single-stage hybrid arch procedure
offers an alternative approach to complex diffuse aortic pathology involving the
arch. Replacement of the ascending aorta provides a safe location for zone 0
stent graft deployment, eliminating complications of proximal deployment in a
native diseased aorta.
PMID- 25125211
TI - Solid self-emulsifying phospholipid suspension (SSEPS) with diatom as a drug
carrier.
AB - We report the application of diatom as a solid carrier for water insoluble drugs
applied in oral drug delivery system based on the self-emulsifying drug delivery
system (SEDDS) caprylocaproyl macrogol-8 glycerides/lecithin/propylene
glycol/caprylic/capric triglyceride. Diatoms are fossilized skeletons of
photosynthetic algae with complex 3-dimensional (3D), porous structure consisting
of amorphous silica, obtained by purification of diatomaceous earth. Different
solid samples of carbamazepine (CBZ) suspension in SEDDS, called solid self
emulsifying phospholipid suspension (SSEPS), were prepared using two methods:
adsorption of CBZ dispersion in SEDDS by gentle mixing with diatoms in mortar
with pestle (Method A) or dispersion of diatoms in ethanol solution of CBZ and
SEDDS components, followed by ethanol evaporation (Method B). Release rate of CBZ
from SSEPS was significantly higher in comparison to pure drug, physical mixture
of diatoms and CBZ as well as solid dispersion of pure CBZ and diatoms obtained
by ethanol evaporation. The dissolution of CBZ from SSEPS sample prepared using
method B was faster than from the sample prepared by the method A. Higher
dissolution for sample prepared by the method B can be attributed to the partial
adsorption (deeper localization) of liquid material inside the pores of diatoms.
Upon storage of the samples under accelerated conditions (40 degrees C and 70%
RH) for 10 weeks no significant changes in CBZ crystallinity and dissolution was
in case of SSEPS, contrary to solid dispersion with increased crystallinity,
indicating that diatoms with adsorbed liquid CBZ-loaded SEPS can maintain initial
CBZ characteristics.
PMID- 25125212
TI - Systematic review to identify and appraise outcome measures used to evaluate
childhood obesity treatment interventions (CoOR): evidence of purpose,
application, validity, reliability and sensitivity.
AB - BACKGROUND: Lack of uniformity in outcome measures used in evaluations of
childhood obesity treatment interventions can impede the ability to assess
effectiveness and limits comparisons across trials. OBJECTIVE: To identify and
appraise outcome measures to produce a framework of recommended measures for use
in evaluations of childhood obesity treatment interventions. DATA SOURCES: Eleven
electronic databases were searched between August and December 2011, including
MEDLINE; MEDLINE In-Process and Other Non-Indexed Citations; EMBASE; PsycINFO;
Health Management Information Consortium (HMIC); Allied and Complementary
Medicine Database (AMED); Global Health, Maternity and Infant Care (all Ovid);
Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCOhost);
Science Citation Index (SCI) [Web of Science (WoS)]; and The Cochrane Library
(Wiley) - from the date of inception, with no language restrictions. This was
supported by review of relevant grey literature and trial databases. REVIEW
METHODS: Two searches were conducted to identify (1) outcome measures and
corresponding citations used in published childhood obesity treatment evaluations
and (2) manuscripts describing the development and/or evaluation of the outcome
measures used in the childhood intervention obesity evaluations. Search 1 search
strategy (review of trials) was modelled on elements of a review by Luttikhuis et
al. (Oude Luttikhuis H, Baur L, Jansen H, Shrewsbury VA, O'Malley C, Stolk RP, et
al. Interventions for treating obesity in children. Cochrane Database Syst Rev
2009;1:CD001872). Search 2 strategy (methodology papers) was built on Terwee et
al.'s search filter (Terwee CB, Jansma EP, Riphagen II, de Vet HCW. Development
of a methodological PubMed search filter for finding studies on measurement
properties of measurement instruments. Qual Life Res 2009;18:1115-23). Eligible
papers were appraised for quality initially by the internal project team. This
was followed by an external appraisal by expert collaborators in order to agree
which outcome measures should be recommended for the Childhood obesity Outcomes
Review (CoOR) outcome measures framework. RESULTS: Three hundred and seventy-nine
manuscripts describing 180 outcome measures met eligibility criteria. Appraisal
of these resulted in the recommendation of 36 measures for the CoOR outcome
measures framework. Recommended primary outcome measures were body mass index
(BMI) and dual-energy X-ray absorptiometry (DXA). Experts did not advocate any
self-reported measures where objective measurement was possible (e.g. physical
activity). Physiological outcomes hold potential to be primary outcomes, as they
are indicators of cardiovascular health, but without evidence of what constitutes
a minimally importance difference they have remained as secondary outcomes
(although the corresponding lack of evidence for BMI and DXA is acknowledged). No
preference-based quality-of-life measures were identified that would enable
economic evaluation via calculation of quality-adjusted life-years. Few measures
reported evaluating responsiveness. LIMITATIONS: Proposed recommended measures
are fit for use as outcome measures within studies that evaluate childhood
obesity treatment evaluations specifically. These may or may not be suitable for
other study designs, and some excluded measures may be more suitable in other
study designs. CONCLUSIONS: The CoOR outcome measures framework provides clear
guidance of recommended primary and secondary outcome measures. This will enhance
comparability between treatment evaluations and ensure that appropriate measures
are being used. Where possible, future work should focus on modification and
evaluation of existing measures rather than development of tools de nova. In
addition, it is recommended that a similar outcome measures framework is produced
to support evaluation of adult obesity programmes. FUNDING: The National
Institute for Health Research Health Technology Assessment programme.
PMID- 25125214
TI - Direct superior tibiofibular joint arthrography demonstrates consistent
communication with the tibiofemoral joint.
PMID- 25125213
TI - Embolus characterization in branch retinal artery occlusion by optical coherence
tomography.
PMID- 25125210
TI - Single genome analysis reveals genetic characteristics of Neuroadaptation across
HIV-1 envelope.
AB - BACKGROUND: The widespread use of highly effective, combination antiretroviral
therapy (cART) has led to a significant reduction in the incidence of HIV
associated dementia (HAD). Despite these advances, the prevalence of HIV-1
associated neurocognitive disorders (HANDs) has been estimated at approximately
40%-50%. In the cART era, the majority of this disease burden is represented by
asymptomatic neurocognitive impairment and mild neurocognitive disorder (ANI and
MND respectively). Although less severe than HAD, these diagnoses carry with them
substantial morbidity. RESULTS: In this cross-sectional study, single genome
amplification (SGA) was used to sequence 717 full-length HIV-1 envelope (env)
clade B variants from the paired cerebrospinal fluid (CSF) and blood plasma
samples of fifteen chronically infected HIV-positive individuals with normal
neurocognitive performance (NCN), ANI and MND. Various degrees of
compartmentalization were found across disease states and history of cART
utilization. In individuals with compartmentalized virus, mean HIV-1 env
population diversity was lower in the CSF than plasma-derived variants. Overall,
mean V1V2 loop length was shorter in CSF-derived quasispecies when compared to
contemporaneous plasma populations, and this was found to correlate with a lower
mean number of N-linked glycosylation sites in this region. A number of discrete
amino acid positions that correlate strongly with compartmentalization in the CSF
were identified in both variable and constant regions of gp120 as well as in
gp41. Correlated mutation analyses further identified that a subset of amino acid
residues in these compartmentalization "hot spot" positions were strongly
correlated with one another, suggesting they may play an important, definable
role in the adaptation of viral variants to the CSF. Analysis of these hot spots
in the context of a well-supported crystal structure of HIV-1 gp120 suggests
mechanisms through which amino acid differences at the identified residues might
contribute to viral compartmentalization in the CSF. CONCLUSIONS: The detailed
analyses of SGA-derived full length HIV-1 env from subjects with both normal
neurocognitive performance and the most common HAND diagnoses in the cART era
allow us to identify novel and confirm previously described HIV-1 env genetic
determinants of neuroadaptation and relate potential motifs to HIV-1 env
structure and function.
PMID- 25125215
TI - Vitamin D supplementation for treatment of seasonal affective symptoms in
healthcare professionals: a double-blind randomised placebo-controlled trial.
AB - BACKGROUND: Low serum 25-hydroxyvitamin D levels (25(OH)D) have been associated
with a higher likelihood of seasonal affective disorder (SAD) and poor mental
well-being, yet firm evidence for either remains lacking. Thus, vitamin D
supplementation may alleviate symptoms associated with SAD. METHODS: This study
was a randomized, single-centre, double-blind, placebo-controlled trial including
healthcare professionals employed in psychiatric and somatic hospitals. 3345
healthcare professionals were invited to participate, 50 participants were
screened, and 34 were able to complete the study. The main inclusion criterion
was 8 points or more on question no. 2 of the Seasonal Pattern Assessment
Questionnaire (SPAQ-SAD). During a 3-month period, the participants received a
daily dose of 70 MUg vitamin D or placebo. The primary outcome was the sum of the
self-reported questionnaire Structured Interview Guide for the Hamilton
Depression Rating Scale, Seasonal Affective Disorders (SIGH-SAD). The secondary
outcome was World Health Organization-Five Well-Being Index (WHO-5) of the
healthcare professionals during the winter period and the exploratory outcome
measures were weight, waist circumference, blood pressure, absenteeism from work
and 25(OH)D. RESULTS: There were no significant between-group differences in SIGH
SAD sums at 12 weeks (p = 0.7 (CI: - 3.27 to 4.81)). However, there was a
significant improvement of primary SIGH-SAD over time from inclusion (autumn
winter) to the completion of the study (winter-spring) for all participants. The
secondary and exploratory outcome measures were all insignificant between
groups.The sums of the SIGH-SAD at 12 weeks were not significantly different [p =
0.701 (CI: 4.81-3.27)] between the groups. There was, however, a significant
improvement in primary SIGH-SAD sums over time from inclusion (autumn-winter) to
the completion of the study (winter-spring) in both groups. The secondary and
explorative outcome measures were not significantly different between groups.
CONCLUSIONS: There were no significant between-group differences in the primary
(SIGH-SAD) and secondary (WH0-5) as well as the exploratory outcome measures
(weight, waist circumference, blood pressure, absenteeism from work and 25(OH)D.
Thus, the study failed to demonstrate an effect of vitamin D on SAD symptoms, but
our findings may be limited by confounders. Furthermore, the study was
underpowered and did not allow us to assess the ability of vitamin D to improve
mood in those with low 25(OH)D. TRIAL REGISTRATION: (
http://www.clinicaltrials.gov registration number: NCT01462058).
PMID- 25125216
TI - Uveitis in patients with late-stage cutaneous melanoma treated with vemurafenib.
AB - IMPORTANCE: This case series highlights the risk of uveitis in patients treated
with vemurafenib for unresectable or metastatic cutaneous melanoma. OBJECTIVE: To
assess the occurrence and severity of uveitis as an adverse effect of vemurafenib
therapy. DESIGN, SETTING, AND PATIENTS: In this observational small case series,
data were collected successively from May 1, 2012, through February 31, 2013,
from patients with clinical signs of ocular inflammation treated with vemurafenib
at the Department of Ophthalmology, Cochin-Hotel-Dieu Hospital. MAIN OUTCOMES AND
MEASURES: Patients' demographics, vemurafenib dosages, and the intervals between
the onset of treatment and the first ocular symptoms were recorded. The
characteristics of ocular inflammatory manifestations were analyzed. The effect
of the discontinuation of vemurafenib therapy on ocular manifestations was
assessed, as well as the effect of rechallenging when vemurafenib was
reintroduced. RESULTS: Seven patients (mean [SD] age, 74.7 [4.0] years) had
uveitis. The vemurafenib dose was 960 mg twice per day in 6 patients and a half
dose in 1 patient. The mean (SD) time until the appearance of ocular signs was
5.6 (2.3) months (range, 19 days to 7 months), and inflammation ranged from mild
or low-grade anterior uveitis to severe explosive panuveitis complicated by
retinal detachment. Signs of ocular inflammation were always bilateral. Optical
coherence tomography revealed a macular edema in only 1 of the 7 patients.
Clinical improvement occurred when vemurafenib therapy was stopped in 5 of 7
patients. The rechallenge at treatment reintroduction was positive in 2 of 7
patients. CONCLUSIONS AND RELEVANCE: This small case series highlights that
uveitis can be a noteworthy adverse effect of vemurafenib therapy in patients
with metastatic cutaneous melanoma. However, these cases of uveitis were usually
restricted to the anterior segment and manageable with local corticosteroid
therapy, which justified the continuation of vemurafenib therapy because the
benefits regarding the patients' survival were greater than the risk to their
vision.
PMID- 25125217
TI - Refractometer assessment of colostral and serum IgG and milk total solids
concentrations in dairy cattle.
AB - BACKGROUND: Estimation of the quantity of colostral IgG or serum IgG absorbed
following ingestion of colostrum by calves is essential for monitoring the
effectiveness of colostrum feeding practices on dairy farms. Milk total solids
concentrations determination is a critical part of quality assessment of
nonsaleable whole milk prior to feeding to calves. To date, on-farm methods to
assess colostral IgG, serum IgG or milk total solids concentrations have been
performed separately with various instruments. The objective of this study was to
evaluate the diagnostic performance of a single electronic, hand-held
refractometer for assessing colostral and serum IgG concentrations and milk total
solids in dairy cattle. Colostral IgG, serum IgG and milk total solids
concentrations were determined by the refractometer. Corresponding analysis of
colostral and serum IgG concentrations were determined by radial immunodiffusion
(RID) while milk total solids were determined by spectrophotometry. Sensitivity
and specificity of the refractometer for colostrum and serum samples were
calculated as determined by RID. Sensitivity and specificity of the refractometer
for milk samples was calculated as determined by spectrophotometry. RESULTS: The
sensitivity of the refractometer was 1 for colostral IgG, serum IgG and milk
total solids determinations. Specificity of the refractometer was 0.66, 0.24 and
0 for colostral IgG, serum IgG and milk total solids determinations,
respectively. The refractometer underestimated colostral IgG, serum IgG and milk
total solids concentrations compared to the concentrations determined by RID or
spectrophotometry. CONCLUSIONS: The refractometer was an acceptable, rapid,
convenient on-farm method for determining colostral IgG and milk total solids.
The refractometer was not an acceptable method for determination of serum IgG
concentrations as it severely underestimated the serum IgG concentrations.
PMID- 25125218
TI - Circulating microRNAs as a marker for liver injury in human immunodeficiency
virus patients.
AB - Human immunodeficiency virus (HIV) and hepatitis virus coinfection amplify and
accelerate hepatic injury. MicroRNAs (miRNAs) are small regulatory RNAs suggested
as biomarkers for liver injury. We analyzed the circulating levels of miRNAs in
HIV patients with regard to the extent and etiology of liver injury. Total RNA
was extracted from 335 serum samples of HIV patients and 22 healthy control
participants using Qiazol. Comprehensive polymerase chain reaction (PCR) array
analyses (768 miRNA) were performed in serum samples of eight HIV, eight HIV/HCV
(hepatitis C virus), six HCV patients, and three healthy controls. Reverse
transcription (RT)-PCR measured levels of miRNA-122, miRNA-22, and miRNA-34a in
serum samples of 335 patients and 19 healthy control participants. Liver injury
and fibrosis in these patients were defined using aspartate aminotransferase
(AST) levels, fibrosis-4 (FIB-4) index and AST-to-platelet ratio index (APRI)
score. The miRNA pattern of HIV/HCV samples showed altered expression of 57 and
33 miRNA compared to HCV and HIV infection, respectively. miRNA-122, miRNA-22,
and miRNA-34a were highly up-regulated in HIV/HCV patients. Analyzing the entire
cohort, these miRNAs were correlated with liver function tests and were
independent predictors of liver injury (AST >2 * ULN). miRNA-122 and miRNA-22
were associated with relevant fibrosis (FIB-4 >1.45; APRI >1). Circulating levels
of miRNA-122 were independent predictors for relevant fibrosis in HIV patients.
Interestingly, miRNA-122 and miRNA-34a levels were higher in HIV/HCV patients,
miRNA-22 levels were highest in HIV/HBV patients, and circulating levels of miRNA
34a correlated positively with illicit drug use and ethanol consumption.
CONCLUSION: Circulating miRNA-122, miRNA-22, and miRNA-34a correlates with the
etiology of liver injury in HIV patients. These biomarkers not only mirror
different mechanisms of hepatic injury, but also are independent predictors of
liver injury in HIV patients.
PMID- 25125220
TI - Ribonuclease A inhibition by carboxymethylsulfonyl-modified xylo- and
arabinopyrimidines.
AB - A group of acidic nucleosides were synthesized to develop a new class of
ribonuclease A (RNase A) inhibitors. Our recent study on carboxymethylsulfonyl
modified nucleosides revealed some interesting results in RNase A inhibition.
This positive outcome triggered an investigation of the role played by secondary
sugar hydroxy groups in inhibiting RNase A activity. Uridines and cytidines
modified with ?SO2 CH2 COOH groups at the 2'- and 3'-positions show good
inhibitory properties with low inhibition constant (Ki ) values in the range of
109-17 MUM. The present work resulted in a set of inhibitors that undergo more
effective interactions with the RNase A active site, as visualized by docking
studies.
PMID- 25125221
TI - Improved psoriasis with weight loss: the role of behavioural factors.
PMID- 25125219
TI - Dietary guideline adherence for gastroesophageal reflux disease.
AB - BACKGROUND: Gastroesophageal reflux disease (GERD) is the most common
gastrointestinal disease, and the cost of health care and lost productivity due
to GERD is extremely high. Recently described side effects of long-term acid
suppression have increased the interest in nonpharmacologic methods for
alleviating GERD symptoms. We aimed to examine whether GERD patients follow
recommended dietary guidelines, and if adherence is associated with the severity
and frequency of reflux symptoms. METHODS: We conducted a population-based cross
sectional study within the Kaiser Permanente Northern California population,
comparing 317 GERD patients to 182 asymptomatic population controls. All analyses
adjusted for smoking and education. RESULTS: GERD patients, even those with
moderate to severe symptoms or frequent symptoms, were as likely to consume
tomato products and large portion meals as GERD-free controls and were even more
likely to consume soft drinks and tea [odds ratio (OR) = 2.01 95% confidence
interval (CI) 1.12-3.61; OR = 2.63 95% CI 1.24-5.59, respectively] and eat fried
foods and high fat diet. The only reflux-triggering foods GERD patients were less
likely to consume were citrus and alcohol [OR = 0.59; 95% CI: 0.35-0.97 for
citrus; OR = 0.41 95% CI 0.19-0.87 for 1 + drink/day of alcohol]. The
associations were similar when we excluded users of proton pump inhibitors.
CONCLUSIONS: GERD patients consume many putative GERD causing foods as frequently
or even more frequently than asymptomatic patients despite reporting symptoms.
These findings suggest that, if dietary modification is effective in reducing
GERD, substantial opportunities for nonpharmacologic interventions exist for many
GERD patients.
PMID- 25125222
TI - Sex steroids as pheromones in mammals: the exceptional role of estradiol.
AB - This article is part of a Special Issue (Chemosignals and Reproduction). Whether
from endogenous or exogenous sources, 17beta-estradiol (E2) has very powerful
influences over mammalian female reproductive physiology and behavior. Given its
highly lipophilic nature and low molecular mass, E2 readily enters excretions and
can be absorbed from exogenous sources via nasal, cutaneous, and other modes of
exposure. Indeed, systemic injection of tritiated estradiol ((3)H-E2) into a male
mouse or bat has been shown to produce significant levels of radioactivity in the
reproductive tissues and brain of cohabiting female conspecifics. Bioactive E2
and other steroids are naturally found in male mouse urine and other excretions,
and males actively direct their urine at proximate females. Very low doses of E2
can mimic the Bruce effect (disruption of peri-implantation pregnancy by novel
males), the Vandenbergh effect (early reproductive maturation induced by novel
males), and male-induced estrus and ovulation. Males' capacities to induce the
Bruce and Vandenbergh effects can both be diminished by manipulations that reduce
their urinary E2. Uterine dynamics during the Bruce and Vandenbergh effects are
consistent with the actions of E2. Collectively, these data demonstrate a
critical role of male-sourced E2 in these major mammalian pheromonal effects.
PMID- 25125223
TI - What is the meaning of a nonresolved viral nucleic acid test-reactive minipool?
AB - BACKGROUND: This study aimed at analyzing the prevalence of hepatitis B virus
(HBV) DNA among hepatitis B surface antigen (HBsAg)-negative donations by cobas
TaqScreen MPX test (Roche Molecular Systems) and discussing the meaning of a
reactive minipool (MP) that does not resolve to an individual donation (ID)
reactive result. STUDY DESIGN AND METHODS: Nucleic acid amplification testing
(NAT) was performed in 12 Chinese blood centers on 826,044 serologic negative
donations in MPs of six. MP-reactive pools that were resolved to ID-reactive
donations were confirmed by Roche TaqMan viral load assays. Antibody to hepatitis
B surface antigen and antibody to hepatitis B core antigen (anti-HBc) results
were also analyzed. Cycle threshold (Ct) values of reactive MPs were analyzed in
relation to the probability of pool resolution. RESULTS: A total of 1267 of
137,674 pools were reactive, of which 839 donations were reactive by ID-NAT. The
MP6 HBV NAT-yield rate lay between 1 in 1600 and 1 in 1000. At MP Ct values equal
or below 37, the probability of pool resolution was approximately 80%. The
prevalence of anti-HBc in ID-reactive donations was 81%. The proportion of
reactive pools that could not be resolved was 36%. The prevalence of anti-HBc in
donations implicated in nonresolved MPs was significantly higher than those in
nonreactive MPs (48% vs. 37%, p = 0.016). CONCLUSION: The anti-HBc data suggest
that approximately 10% of nonresolved MPs contain HBV DNA from a low-viral-load
occult carrier. We consider ID-NAT resolution testing in duplicate to minimize
HBV transmission risk associated with transfusing nonreactive donations
implicated in reactive MPs.
PMID- 25125224
TI - Quantification of the triglyceride fatty acid composition with 3.0 T MRI.
AB - The aim of this work was to validate a sequential method for quantifying the
triglyceride fatty acid composition with 3.0 T MRI. The image acquisition was
performed with a 3D spoiled gradient multiple echo sequence. A specific phase
correction algorithm was implemented to correct the native phase images for wrap,
zero- and first-order phase and rebuild the real part images. Then, using a model
of a fat (1)H MR spectrum integrating nine components, the number of double bonds
(ndb) and the number of methylene-interrupted double bonds (nmidb) were derived.
The chain length (CL) was obtained from these parameters using heuristic
approximation. Validations were performed on different vegetable oils whose
theoretical fatty acid composition was used as reference and in five human
subjects. In vivo measurements were made in the liver and in the subcutaneous and
visceral adipose tissues. Linear regressions showed strong correlations between
ndb and nmidb quantified with MRI and the theoretical values calculated using oil
composition. Mean ndb/nmidb/CL were 1.80 +/- 0.25/0.51 +/- 0.21/17.43 +/- 0.07,
2.72 +/- 0.31/0.94 +/- 0.16/17.47 +/- 0.08 and 2.53 +/- 0.21/0.84 +/- 0.14/17.43
+/- 0.07 in the liver, subcutaneous and visceral adipose tissues respectively.
The results suggest that the triglyceride fatty acid composition can be assessed
in human fatty liver and adipose tissues with a clinically relevant MRI method at
3.0 T.
PMID- 25125227
TI - Designing technology to meet the therapeutic demands of acute renal injury in
neonates and small infants.
AB - Within paediatric intensive care units (PICU), clinicians face an increasing
demand to support neonates and small infants with acute renal injury or
medication-resistant oedema. Of all PICU admissions, fluid overload or a
requirement for renal replacement therapy (RRT) is a poor prognostic factor,
resulting in death in 25-50 % of such babies. For those who survive, RRT is
supportive until kidney recovery, but up to 30 % of babies may have chronic
kidney sequelae. Owing to their size, neonates and small infants present specific
challenges for dialysis. Dialysis technology was designed for use in adults and
had to be adapted for pediatric use, creating a less than ideal treatment
environment fraught with complications. Consequently, wherever possible, the vast
majority of physicians default to peritoneal dialysis. Clinicians now have access
to two new dialysis systems with technology specifically designed for use in
babies ranging from 800 g to 8 kg: the CARPEDIEM and Nidus exhibit preliminary
data that demonstrates both purification and ultrafiltration capability, with
safety records that exceed any existing systems presently in practice. These are
truly exciting times, as these systems have the potential to revolutionise how
such babies in the PICU are treated.
PMID- 25125226
TI - Viral surveillance and subclinical viral infection in pediatric kidney
transplantation.
AB - The more potent immunosuppressive therapy that has successfully reduced the
incidence of acute rejection and improved graft outcomes has also resulted in a
higher incidence of viral complications. Sensitive molecular methods now allow
for the detection of subclinical viral infection, which is increasingly
recognized due to the adoption of routine post-transplant viral surveillance
protocols. The goal of viral surveillance is the detection of subclinical viral
infection that triggers an intervention; one that either prevents progression to
viral disease or leads to early diagnosis of viral disease, which is associated
with improved outcomes. Knowledge of the epidemiology and natural history of
subclinical viral infection and viral disease, as well as patient-specific risk
factors, is required to establish the optimal surveillance schedule which
achieves the goal of early diagnosis. Evidence that detection of subclinical
viral infection can impact viral disease is variable depending on the virus. This
review will summarize the current data on the role of viral surveillance for BK
virus (BKV), cytomegalovirus (CMV), and the Epstein-Barr virus (EBV) in the
pediatric kidney transplant population.
PMID- 25125228
TI - A 2-year-old presents following methanol ingestion with serum creatinine of 8.6
mg/dl: Questions.
PMID- 25125225
TI - Higher levels of cystatin C are associated with worse cognitive function in older
adults with chronic kidney disease: the chronic renal insufficiency cohort
cognitive study.
AB - OBJECTIVES: To determine the association between cognition and levels of cystatin
C in persons with chronic kidney disease (CKD). DESIGN: Prospective observational
study. SETTING: Chronic Renal Insufficiency Cohort Cognitive Study. PARTICIPANTS:
Individuals with a baseline cognitive assessment completed at the same visit as
serum cystatin C measurement (N = 821; mean age 64.9, 50.6% male, 48.6% white).
MEASUREMENTS: Levels of serum cystatin C were categorized into tertiles;
cognitive function was assessed using six neuropsychological tests. Scores on
these tests were compared across tertiles of cystatin C using linear regression
and logistic regression to examine the association between cystatin C level and
cognitive performance (1 standard deviation difference from the mean). RESULTS:
After multivariable adjustment for age, race, education, and medical
comorbidities in linear models, higher levels of cystatin C were associated with
worse cognition on the modified Mini-Mental State Examination, Buschke Delayed
Recall, Trail-Making Test Part (Trails) A and Part B, and Boston Naming (P < .05
for all). This association remained statistically significant for Buschke Delayed
Recall (P = .01) and Trails A (P = .03) after additional adjustment for estimated
glomerular filtration rate (eGFR). The highest tertile of cystatin C was
associated with greater likelihood of poor performance on Trails A (odds ratio
(OR) = 2.17, 95% confidence interval (CI) = 1.16-4.06), Trails B (OR = 1.89, 95%
CI = 1.09-3.27), and Boston Naming (OR = 1.85, 95% CI = 1.07-3.19) than the
lowest tertile after multivariate adjustment in logistic models. CONCLUSION: In
individuals with CKD, higher serum cystatin C levels were associated with worse
cognition and greater likelihood of poor cognitive performance on attention,
executive function, and naming. Cystatin C is a marker of cognitive impairment
and may be associated with cognition independent of eGFR.
PMID- 25125229
TI - Haemodialysing babies weighing <8 kg with the Newcastle infant dialysis and
ultrafiltration system (Nidus): comparison with peritoneal and conventional
haemodialysis.
AB - BACKGROUND: To compare the efficacy of the Newcastle infant dialysis and
ultrafiltration system (Nidus) with peritoneal dialysis (PD) and conventional
haemodialysis (HD) in infants weighing <8 kg. METHODS: We compared the urea,
creatinine and phosphate clearances, the ultrafiltration precision, and the
safety of the Nidus machine with PD in 7 piglets weighing 1-8 kg, in a planned
randomised cross-over trial in babies, and in babies for whom no other therapy
existed, some of whom later graduated to conventional HD. RESULTS: Two babies
entered the randomised trial; 1 recovered rapidly on PD, the other remained on
the Nidus as PD failed. Additionally, 9 babies were treated on the Nidus on
humanitarian grounds: 3 because of failed PD, and 3 with permanent kidney failure
later converted to conventional HD. We haemodialysed 10 babies weighing between
1.8 and 5.9 kg for 2,475 h during 354 Nidus sessions without any clinically
important incidents, and without detectable haemolysis. Single-lumen vascular
access was used with no blood priming of circuits. The urea, creatinine and
phosphate clearances using the Nidus were around 1.5 to 2.0 ml/min in piglets and
babies, and were consistently higher than PD clearances, which ranged from about
0.2 to 0.8 ml/min (p <= 0.0002 for each chemical). Ultrafiltration was achieved
to microlitre precision by the Nidus, but varied widely with PD. Fluid removal
using conventional HD was imprecise and resulted in some hypovolaemic episodes
requiring correction. CONCLUSION: The Nidus can provide HD in the Pediatric
Intensive Care Unit (PICU) and outpatient intermittent HD without blood priming
for babies weighing <8 kg, It generates higher dialysis clearances than PD, and
delivers more precise ultrafiltration control than either PD or conventional HD.
PMID- 25125231
TI - Global and cyp19a1a gene specific DNA methylation in gonads of adult rare minnow
Gobiocypris rarus under bisphenol A exposure.
AB - As a weak estrogenic chemical, bisphenol A (BPA) has been extensively studied for
reproductive toxicity and the effects on the steroidogenesis. In the present
study, we aim to explore the effects of BPA on epigenetic modification in rare
minnow Gobiocypris rarus. We have detected the global and cyp19a1a gene specific
DNA methylation in gonads of adult G. rarus under BPA exposure. The global DNA
methylation level was significantly increased in testis of the male fish exposed
to BPA for 7 days, and it was significantly increased in the ovary following 35
days exposure. DNA methyltransferases (DNMTs) catalyze the transfer of a methyl
moiety from S-adenosyl-l-methionine to the cytosine of a CpG dinucleotide. The
alteration of the detected dnmts mRNA expression could affect the global DNA
methylation levels following 15MUg/L BPA exposure. Cytochrome P450 aromatase
(CYP19A1A), is responsible for the conversion of androgens into estrogens, which
plays a vital role in estrogen synthesis in gonads. In the present study, the
methylation level of ovarian cyp19a1a gene was significantly suppressed and
stimulated by 7- and 35-day BPA exposure, respectively. There was a significant
negative correlation between cyp19a1a mRNA expression and methylation levels of
the four CpGs at the 5' flanking region in the ovary of adult G. rarus following
BPA exposure. So we hypothesize that there are some association between the
reproductive toxicity of BPA and the global DNA methylation under BPA exposure.
And the alteration of cyp19a1a expression in female G. rarus by BPA might
attribute to the change of its DNA methylation status.
PMID- 25125232
TI - From a "perfect storm" to "smooth sailing": policymaker perspectives on
implementation and sustainment of an evidence-based practice in two states.
AB - Policymakers shape implementation and sustainment of evidence-based practices
(EBPs), whether they are developing or responding to legislation and policies or
negotiating public sector resource constraints. As part of a large mixed-method
study, we conducted qualitative interviews with 24 policymakers involved in
delivery of the same EBP in two U.S. states. We analyzed transcripts via open and
focused coding techniques to identify the commonality, diversity, and complexity
of implementation challenges; approaches to overcoming those challenges; and the
importance of system-level contextual factors in ensuring successful
implementation. Key findings centered on building support and leadership for
EBPs; funding and contractual strategies; partnering with stakeholders; tackling
challenges via proactive planning and problem solving; and the political, legal,
and systemic pressures affecting EBP longevity. The policymaker perspectives
offer guidance on nurturing system and organizational practice environments to
achieve positive outcomes and for optimally addressing macro-level influences
that bear upon the instantiation of EBPs in public sector child welfare systems.
PMID- 25125233
TI - The relationship between child maltreatment and substance abuse treatment
outcomes among emerging adults and adolescents.
AB - Emerging adulthood is the period of greatest risk for problematic substance use.
The primary aim of the current study was to examine the relationship between a
broad measure of child maltreatment and several key outcomes for a large clinical
sample of emerging adults (n = 858) and adolescents (n = 2,697). The secondary
aim was to examine the extent to which the relationship between child
maltreatment and treatment outcomes differed between emerging adults and
adolescents. Multilevel latent growth curve analyses revealed emerging adults and
adolescents who experienced child maltreatment reported significantly greater
reductions over time on several treatment outcomes (e.g., substance use,
substance-related problems, and emotional problems). Overall, analyses did not
support differential relationships between child maltreatment and changes over
time in these substance use disorder treatment outcomes for emerging adults and
adolescents. The one exception was that although emerging adults with child
maltreatment did reduce their HIV risk over time, their improvements were not as
great as were the improvements in HIV risk reported by adolescents who had
experienced child maltreatment.
PMID- 25125234
TI - [Acute on chronic respiratory failure in interstitial pneumonias].
AB - BACKGROUND: Acute exacerbations of idiopathic interstitial pneumonias and
exacerbations of pleuropulmonary disease in connective tissue diseases are
associated with a high mortality. DIAGNOSTIC PROCEDURES: They have to be
differentiated from respiratory failure in patients with interstitial lung
disease as a result of infections, pulmonary embolism, cardiac failure and drug
toxicity, because the latter can be treated causally. The extent and the
invasivity of diagnostic procedures have to be adopted to the patient's
situation. A rapid diagnosis is important in order to initiate therapies
(antibiotics, anticoagulation, immunosuppression) in treatable causes of
exacerbations. IMPORTANCE OF VENTILATION: The prognosis for patients who are
under invasive mechanical ventilation in acute exacerbations of interstitial lung
disease is poor. Especially in acute exacerbations of idiopathic pulmonary
fibrosis (IPF), there is no general recommendation for either invasive or for
noninvasive ventilation. In acute exacerbations of other subtypes of interstitial
pneumonia, either idiopathic or as a pulmonary manifestation of connective tissue
disease, and in all secondary exacerbations of idiopathic interstitial pneumonias
which offer further treatment options, the decision about mechanical ventilation
requires a differentiated assessment. LUNG TRANSPLANTATION: In younger patients
with interstitial lung disease and a progressive disease, indication for lung
transplantation should be made early and before an exacerbation. If patients
listed for lung transplantation experience an acute exacerbation, bridging-to
transplant has to be discussed with the transplant unit. In cases without further
causal treatment options palliative care must be initiated.
PMID- 25125235
TI - [Physiotherapy in intensive care medicine].
AB - BACKGROUND: A high amount of recently published articles and reviews have already
focused on early mobilisation in intensive care medicine. However, in the
clinical setting the problem of its practicability remains as each professional
group in the mobility team has its own expectations concerning the interventions
made by physiotherapy. Even though there are as yet no standard operation
procedures (SOP), there do exist distinctive mobilisation concepts that are well
implemented in certain intensive care units
(http://www.fruehmobilisierung.de/Fruehmobilisierung/Algorithmen.html). AIM: Due
to these facts and the urgent need for SOPs this article presents the
physiotherapeutic concept for the treatment of patients in the intensive care
unit which has been developed by the author: First the patients' respiratory and
motor functions have to be established in order to classify the patients and
allocate them to their appropriate group (one out of three) according to their
capacities; additionally, the patients are analysed by checking their so-called
"surrounding conditions". Following these criteria a therapy regime is developed
and patients are treated accordingly. By constant monitoring and re-evaluation of
the treatment in accordance with the functions of the patient a dynamic system
evolves. "Keep it simple" is one of the key features of that physiotherapeutic
concept. Thus, a manual for the classification and the physiotherapeutic
treatment of an intensive care patient was developed. METHODS: In this article it
is demonstrated how this concept can be implemented in the daily routine of an
intensive care unit. Physiotherapy in intensive care medicine has proven to play
an important role in the patients' early rehabilitation if the therapeutic
interventions are well adjusted to the needs of the patients. A team of nursing
staff, physiotherapists and medical doctors from the core facility for medical
intensive care and emergency medicine at the medical university of Innsbruck
developed the "Mobilisation Concept for the Multidisciplinary Treatment of the
Intensive Care Patient" following the principles of the physiotherapeutic concept
mentioned above and published it online on the homepage of the German network for
early mobilisation
(http://www.fruehmobilisierung.de/Fruehmobilisierung/Algorithmen.html) in spring
2012. The biggest challenge was to find one common language for all professional
groups to define the aims of mobilisation. RESULTS: The success of the
implementation becomes apparent in a well structured and coordinated procedure of
early mobilisation, as all partners of the rehabilitation team apply adequate
treatments. As a result the patients receive the appropriate treatment at the
appropriate time which greatly supports their convalescence.
PMID- 25125237
TI - Organ donation video messaging: differential appeal, emotional valence, and
behavioral intention.
AB - Video narratives increasingly are used to draw the public's attention to the need
for more registered organ donors. We assessed the differential impact of donation
messaging videos on appeal, emotional valence, and organ donation intentions in
781 non-registered adults. Participants watched six videos (four personal
narratives, one informational video without personal narrative, and one unrelated
to donation) with or without sound (subtitled), randomly sequenced to minimize
order effects. We assessed appeal, emotional valence, readiness to register as
organ donors, and donation information-seeking behavior. Compared to other video
types, one featuring a pediatric transplant recipient (with or without sound)
showed more favorable appeal (p < 0.001), generated more positive emotional
valence (p < 0.01), and had the most favorable impact on organ donor willingness
(p < 0.001). Ninety-five (12%) participants clicked through to a donation website
after viewing all six videos. Minority race (OR = 1.94, 95% CI = 1.20, 3.13, p =
0.006), positive change in organ donor readiness (OR = 0.26, 95% CI = 0.14, 0.48,
p < 0.001), and total positive emotion (OR = 1.05, 95% CI = 1.03, 1.07, p <
0.001) were significant multivariable predictors of clicking through to the
donation website. Brief, one-min videos can have a very dramatic and positive
impact on willingness to consider donation and behavioral intentions to register
as an organ donor.
PMID- 25125238
TI - BDNF val66met genotype and schizotypal personality traits interact to influence
probabilistic association learning.
AB - The brain derived neurotrophic factor (BDNF) val66met polymorphism rs6265
influences learning and may represent a risk factor for schizophrenia. Healthy
people with high schizotypal personality traits display cognitive deficits that
are similar to but not as severe as those observed in schizophrenia and they can
be studied without confounds of antipsychotics or chronic illness. How genetic
variation in BDNF may impact learning in individuals falling along the
schizophrenia spectrum is unknown. We predicted that schizotypal personality
traits would influence learning and that schizotypal personality-based
differences in learning would vary depending on the BDNF val66met genotype.
Eighty-nine healthy adults completed the Schizotypal Personality Questionnaire
(SPQ) and a probabilistic association learning test. Blood samples were genotyped
for the BDNF val66met polymorphism. An ANOVA was performed with BDNF genotype
(val homozygotes and met-carriers) and SPQ score (high/low) as grouping variables
and probabilistic association learning as the dependent variable. Participants
with low SPQ scores (fewer schizotypal personality traits) showed significantly
better learning than those with high SPQ scores. BDNF met-carriers displaying few
schizotypal personality traits performed best, whereas BDNF met-carriers
displaying high schizotypal personality traits performed worst. Thus, the BDNF
val66met polymorphism appears to influence probabilistic association learning
differently depending on the extent of schizotypal personality traits displayed.
PMID- 25125239
TI - The role of serotonin in adult hippocampal neurogenesis.
AB - Serotonin is probably best known for its role in conveying a sense of
contentedness and happiness. It is one of the most unique and pharmacologically
complex monoamines in both the peripheral and central nervous system (CNS).
Serotonin has become in focus of interest for the treatment of depression with
multiple serotonin-mimetic and modulators of adult neurogenesis used clinically.
Here we will take a broad view of serotonin from development to its physiological
role as a neurotransmitter and its contribution to homeostasis of the adult
rodent hippocampus. This chapter reflects the most significant findings on
cellular and molecular mechanisms from neuroscientists in the field over the last
two decades. We illustrate the action of serotonin by highlighting basic receptor
targeting studies, and how receptors impact brain function. We give an overview
of recent genetically modified mouse models that differ in serotonin availability
and focus on the role of the monoamine in antidepressant response. We conclude
with a synthesis of the most recent data surrounding the role of serotonin in
activity and hippocampal neurogenesis. This synopsis sheds light on the
mechanisms and potential therapeutic model by which serotonin plays a critical
role in the maintenance of mood.
PMID- 25125240
TI - Spontaneous recovery from extinction in the infant rat.
AB - Within the Pavlovian conditioning framework, extinction is a procedure in which,
after conditioning, the conditioned stimulus (CS) is repeatedly presented without
the unconditioned stimulus (US). During this procedure the conditioned response
(CR) is gradually attenuated. It has been suggested that extinction during the
early stages of ontogeny is a qualitatively different process from extinction in
adulthood: during infancy, extinction may result in erasure of the memory, while
during adulthood extinction involves new learning. This conclusion was supported
by studies showing that renewal, reinstatement or spontaneous recovery procedures
were not effective during infancy for recovering the CR once it had been
extinguished. These studies used the freezing response as the only behavioral
index, although some recent evidence indicates that the absence of freezing after
conditioning or after extinction does not necessarily imply a deficit in memory,
and that other behavioral indexes may be more sensitive to detecting conditioning
effects. The goal of the present study was to analyze extinction in preweanling
rats by examining the possibility of the spontaneous recovery of a conditioned
fear response, measured through a different set of mutually-exclusive behaviors
that constitute an exhaustive ethogram, and including control groups (Experiment
1: US-Only and CS-Only; Experiment 2: US-Only, CS-Only and Unpaired) in order to
examine whether non-associative learning may explain quantitative or qualitative
changes in the frequency of specific responses during extinction or recovery.
Extinction produced changes in the expression of freezing, grooming and
exploration, and the clearest evidence of spontaneous recovery came from the
analysis of freezing behavior. The pattern of behavior observed during extinction
is compatible with theoretical approaches which consider different dynamic
behavioral systems, and it also fit in well with a molar approach to the analysis
of behavior, which considers that extinction involves a transition from one
allocation of time among behaviors to another allocation, rather than a loss of
strength in any particular discrete response. These results have implications for
the study of extinction during infancy, since they are compatible with the
hypothesis that the original memory survives extinction, and highlight the
importance of control conditions for detecting this effect during this
ontogenetic period.
PMID- 25125241
TI - Patient expectations in day surgery unit: our experience.
PMID- 25125242
TI - Laser all-ceramic crown removal-a laboratory proof-of-principle study-phase 2
crown debonding time.
AB - BACKGROUND AND OBJECTIVES: The removal of all-ceramic crowns is a time consuming
procedure in the dental office. Little research has been done in alternative
removal techniques for all-ceramic crowns. The objective of the second phase of
this proof-of-principle laboratory pilot study was to evaluate whether Ivoclar
Vivadent all-ceramic crowns can be efficiently removed from natural teeth without
damage to the underlying tooth structure using an Erbium laser. STUDY
DESIGN/MATERIALS AND METHODS: The ceramic materials used were IPS E.max CAD
Lithium-disilicate (LS2 ) (E.max CAD) and IPS E.max ZirCAD Zirconium-oxide (ZrO2
) (ZirCAD) (Ivoclar, Vivadent, Liechtenstein). Molars, either as stand-alone
teeth or placed in an artificial row of teeth, were prepared to receive all
ceramic crowns. Copings and full contour crowns with either featheredge or
regular margins were produced. The all-ceramic crowns were bonded to the teeth
with Ivoclar Multilink Automix. The time for Er:YAG laser debonding of each crown
was then measured. The Er:YAG (LiteTouch, Syneron, Yokneam, Israel) was used with
an 1,100 um diameter fiber tip with energies up to 600 mJ per pulse (wavelength
2,940 nm, 10 Hz repetition rate, pulse duration 100 us at 126 mJ/pulse, and 400
us at 590 mJ/pulse). The irradiation was applied at a distance of 10 mm from the
crown surface following a defined pattern. Air-water spray was applied to the
crowns at a rate of 67 ml/minute. RESULTS: All of the all-ceramic crowns were
successfully debonded with the laser. On average, an all-ceramic E.max CAD crown
was debonded in 190 +/- 92 seconds (average +/- SD). The debonding time for
ZirCAD featheredge crowns was 226 +/- 105 seconds and for ZirCAD crowns with
regular margins it was 312 +/- 102 seconds. No crowns fractured and no damage to
the underlying dentin was detected. The bonding cement deteriorated due to the
Er:YAG irradiation. Additionally, no carbonization at the dentin/cement interface
was observed. CONCLUSION: Er:YAG laser energy can successfully be used to
efficiently debond all-ceramic full contour crowns from natural teeth without
damage to the underlying tooth structure. Lasers Surg. Med. 46:636-643, 2014. (c)
2014 Wiley Periodicals, Inc.
PMID- 25125236
TI - Genetic heterogeneity in Cornelia de Lange syndrome (CdLS) and CdLS-like
phenotypes with observed and predicted levels of mosaicism.
AB - BACKGROUND: Cornelia de Lange syndrome (CdLS) is a multisystem disorder with
distinctive facial appearance, intellectual disability and growth failure as
prominent features. Most individuals with typical CdLS have de novo heterozygous
loss-of-function mutations in NIPBL with mosaic individuals representing a
significant proportion. Mutations in other cohesin components, SMC1A, SMC3, HDAC8
and RAD21 cause less typical CdLS. METHODS: We screened 163 affected individuals
for coding region mutations in the known genes, 90 for genomic rearrangements, 19
for deep intronic variants in NIPBL and 5 had whole-exome sequencing. RESULTS:
Pathogenic mutations [including mosaic changes] were identified in: NIPBL 46 [3]
(28.2%); SMC1A 5 [1] (3.1%); SMC3 5 [1] (3.1%); HDAC8 6 [0] (3.6%) and RAD21 1
[0] (0.6%). One individual had a de novo 1.3 Mb deletion of 1p36.3. Another had a
520 kb duplication of 12q13.13 encompassing ESPL1, encoding separase, an enzyme
that cleaves the cohesin ring. Three de novo mutations were identified in ANKRD11
demonstrating a phenotypic overlap with KBG syndrome. To estimate the number of
undetected mosaic cases we used recursive partitioning to identify discriminating
features in the NIPBL-positive subgroup. Filtering of the mutation-negative group
on these features classified at least 18% as 'NIPBL-like'. A computer composition
of the average face of this NIPBL-like subgroup was also more typical in
appearance than that of all others in the mutation-negative group supporting the
existence of undetected mosaic cases. CONCLUSIONS: Future diagnostic testing in
'mutation-negative' CdLS thus merits deeper sequencing of multiple DNA samples
derived from different tissues.
PMID- 25125243
TI - Abdominal ultrasound-guided transvaginal myometrial core needle biopsy for the
definitive diagnosis of suspected adenomyosis in 1032 patients: a retrospective
study.
AB - STUDY OBJECTIVE: To assess the results of abdominal ultrasound-guided
transvaginal myometrial core needle biopsy (CNB) for the definitive diagnosis of
adenomyosis. DESIGN: Retrospective study (Canadian Task Force classification II
3). SETTING: Private practice. PATIENTS: A total of 1032 consecutive
premenopausal women aged 22 to 53 years who had undergone myometrial CNB and
uterine-preserving surgery to treat adenomyosis, which was preliminarily
diagnosed on the basis of symptoms and ultrasonographic findings. INTERVENTION:
Transvaginal myometrial CNB under abdominal ultrasound guidance. MEASUREMENTS AND
MAIN RESULTS: The mean age of the 1032 patients was 41.4 years (range, 22-53
years); 61% were aged 40 to 49 years, and 33% were aged 30 to 39 years. The mean
Pictorial Blood Loss Assessment Chart (PBAC) score was 271.1, and total pain
score was 11.79. The mean anterior myometrial thickness was 2.79 cm (range, 0.7
8.7 cm), and the posterior myometrial thickness was 3.72 cm (range, 1.1-9.4 cm).
A total of 2596 myometrial tissue cores were obtained from thickened myometrium
via abdominal ultrasound-guided transvaginal myometrial CNB. At histopathologic
examination the tissue cores demonstrated adenomyosis in 2167, myometrial
hypertrophy in 343, and leiomyoma in 86. Patients were classified into a
concordant group (adenomyosis only, adenomyosis plus hypertrophy, and adenomyosis
plus leiomyoma; n = 951) and a discordant group (hypertrophy and leiomyoma; n =
81), depending on conformance between the pathologic result and the preliminary
ultrasonographic diagnosis. The study showed a 92.26% concordance rate of
adenomyosis between the transvaginal myometrial CNB and ultrasonographic
diagnoses. The mean number of tissue cores in the discordant (n = 2.12) and
concordant (n = 2.55) groups differed significantly (p < .05). CONCLUSION:
Abdominal ultrasound-guided transvaginal myometrial CNB can be used in the
definitive diagnosis of clinically and/or sonographically suspected adenomyosis
in patients undergoing uterine-preserving surgery. Future research should focus
on improving the definitive diagnostic rate of adenomyosis by using transvaginal
myometrial CNB.
PMID- 25125244
TI - Incisional negative pressure wound therapy after hemiarthroplasty for femoral
neck fractures - reduction of wound complications.
AB - The aim of the study was to evaluate the use of incisional negative pressure
wound therapy (iNPWT) in wound healing after femoral neck fracture (FNF) treated
with hip hemiarthroplasty (HA) and its influence on postoperative seromas, wound
secretion, as well as time and material consumption for dressing changes. The
study is a prospective randomised evaluation of iNPWT in patients with large
surgical wounds after FNF. Patients were randomised either to be treated by iNPWT
(group A) or a standard wound dressing (group B). Follow-up included ultrasound
measurements of seroma volumes on postoperative days 5 and 10, duration of wound
secretion, and time and material spent for wound dressing changes. For comparison
of the means, we used the t-test for independent samples, P > 0.05 was considered
significant. There were 21 patients randomised in this study. Group A (11
patients, 81.6 +/- 5.2 years of age) developed a seroma of 0.257 +/- 0.75 cm(3)
after 5 days and had a secretion of 0.9 +/- 1.0 days, and the total time for
dressing changes was 14.8 +/- 3.9 minutes, whereas group B (ten patients, 82.6 +/
8.6 years of age) developed a seroma of 3.995 +/- 5.01 cm(3) after 5 days and
had a secretion of 4.3 +/- 2.45 days, and the total time for dressing changes was
42.9 +/- 11.0 minutes. All mentioned differences were significant. iNPWT has been
used on many different types of traumatic and non-traumatic wounds. This
prospective, randomised study has demonstrated decreased development of
postoperative seromas, reduction of total wound secretion days and reduction of
needed time for dressing changes.
PMID- 25125245
TI - Laryngoscopic characteristics in vocal leukoplakia: inter-rater reliability and
correlation with histology grading.
AB - OBJECTIVES/HYPOTHESIS: Vocal cord leukoplakia is a clinical diagnosis that
comprises a spectrum of benignities, premalignancies, and malignancies. Accurate
recordings of the visual characteristics of the affected area are important for
communication between physicians and are helpful in further management. The
objective of this study was to determine the laryngoscopic characteristics among
patients with vocal cord leukoplakia and the reliability of examinations between
different raters. STUDY DESIGN: Retrospective chart review conducted in a
tertiary referral center in Taiwan. METHODS: From January 2010 to April 2013, 107
consecutive patients with vocal leukoplakia who had accepted excisional biopsy
were recruited and classified into two groups according to histologic findings.
The patients without clear preoperative flexible laryngoscope images stored in
the picture archiving and communication system were excluded. There were 68
patients who met the inclusion criteria, and the preoperative laryngoscope images
were reviewed by two laryngologists. The inter-rater reliabilities of the
recordings were assessed. Correlation between the variables and histologic
classification was also performed. RESULTS: The inter-rater reliability of the
assessment was significant in the recordings of color, texture, size, hyperemia,
thickness, and symmetry (kappa = 0.267 to 0.573, P < .05) but not in vocal cord
edema. The laryngoscopic findings including color, texture, size, and hyperemia
were associated with the grade of dysplasia (P < .05). CONCLUSIONS: The specific
proposed laryngoscopic characteristics are consistent in the recordings between
raters and can be potentially used for stratifying patients' risk. LEVEL OF
EVIDENCE: 4.
PMID- 25125247
TI - Guide for bougie as an adjunct for an anterior larynx.
PMID- 25125248
TI - Accuracy of manual entry of drug administration data into an anesthesia
information management system.
AB - PURPOSE: Data on drug administration are entered manually into anesthesia
information management systems (AIMS). This study examined whether these data are
accurate regarding drug name, dose administered, and time of administration, and
whether the stage of anesthesia influences data accuracy. METHODS: Real-time
observational data on drug administration during elective operations were
compared with computerized information on drug administration entered by
anesthesiologists. A trained observer (K.D.) performed the observations. RESULTS:
Data were collected during 57 operations which included 596 separate occasions of
drug administration by 22 anesthesiologists. No AIMS records were found for 90
(15.1%) occasions of drug administration (omissions), while there were 11 (1.8%)
AIMS records where drug administration was not observed. The AIMS and observer
data matched for drug name on 495 of 596 (83.1%) occasions, for dose on 439 of
495 (92.5%) occasions, and for time on 476 of 495 (96.2%) occasions. Amongst the
90 omitted records, 34 (37.8%) were for vasoactive drugs with 24 (27.7%) for
small doses of hypnotics. Omissions occurred mostly during maintenance: 50 of 153
(24.6%), followed by induction: 30 of 325 (9.2%) and emergence: 10 of 57 (17.5%)
(P < 0.001). Time and dose inaccuracies occurred mainly during induction,
followed by maintenance and emergence; time inaccuracies were 7/325 (8.3%),
10/203 (4.9%), and 0/57 (0%), respectively (P = 0.07), and dose inaccuracies were
15/325 (4.6%), 3/203 (1.5%), and 1/57 (1.7%), respectively (P = 0.11).
CONCLUSION: The range of accuracy varies when anesthesiologists manually enter
drug administration data into an AIMS. Charting omissions represent the largest
cause of inaccuracy, principally by omissions of records for vasopressors and
small doses of hypnotic drugs. Manually entered drug administration data are not
without errors. Accuracy of entering drug administration data remains the
responsibility of the anesthesiologist.
PMID- 25125250
TI - From the Journal archives: gastric fluid volume and pH in elective patients
following unrestricted oral fluid until three hours before surgery.
PMID- 25125249
TI - Reversal of high spinal anesthesia with cerebrospinal lavage after inadvertent
intrathecal injection of local anesthetic in an obstetric patient.
AB - PURPOSE: High or total spinal anesthesia commonly results from accidental
placement of an epidural catheter in the intrathecal space with subsequent
injection of excessive volumes of local anesthetic. Cerebrospinal lavage has been
shown to be effective at reversing the effects of high/total spinal anesthesia
but is rarely considered in obstetric cases. Here, we describe the use of
cerebrospinal lavage to prevent potential complications from high/total spinal
anesthesia after unintentional placement of an intrathecal catheter in a
labouring obstetric patient. CLINICAL FEATURES: A 34-yr-old female presented to
the labour and delivery unit in active labour. Epidural anesthesia was initiated,
and after the first bolus dose, the patient experienced lower extremity motor
block and shortness of breath. A high spinal was confirmed, and cerebrospinal
lavage was performed. In total, 40 mL of cerebrospinal fluid (CSF) were exchanged
for an equal volume of normal saline. The patient's breathing difficulties and
motor block resolved quickly, and a new epidural catheter was placed after
removal of the spinal catheter. Pain control was effective, and the patient
delivered a healthy baby. CONCLUSION: We show that exchange of CSF for normal
saline can be used successfully to manage a high spinal in an obstetric patient.
Our results suggest that CSF lavage could potentially be an important and helpful
adjunct to the conventional supportive management of obstetric patients in the
event of inadvertent high or total spinal anesthesia.
PMID- 25125246
TI - Lingual traction to facilitate fibreoptic intubation in patients with difficult
airways under general anesthesia.
PMID- 25125251
TI - Blind nasal intubation: teaching a dying art.
PMID- 25125252
TI - Providing quality in anesthesia care in low- and middle-income countries.
PMID- 25125254
TI - Addressing variant pathogenicity: the TorsinA (TOR1A) gene as a model.
PMID- 25125257
TI - CHK it out! Blocking WEE kinase routs TP53 mutant cancer.
AB - Mutations in TP53, encoding the master tumor suppressor p53, have posed a
developmental therapeutic dilemma due to inability to target loss of function.
Inhibition of WEE1 or CHK1 kinase, negative regulators of the G2-M checkpoint,
selectively sensitizes p53-deficient cells to exogenous DNA damage, abrogating G2
arrest and precipitating mitotic catastrophe.
PMID- 25125258
TI - Design of phase I combination trials: recommendations of the Clinical Trial
Design Task Force of the NCI Investigational Drug Steering Committee.
AB - Anticancer drugs are combined in an effort to treat a heterogeneous tumor or to
maximize the pharmacodynamic effect. The development of combination regimens,
while desirable, poses unique challenges. These include the selection of agents
for combination therapy that may lead to improved efficacy while maintaining
acceptable toxicity, the design of clinical trials that provide informative
results for individual agents and combinations, and logistic and regulatory
challenges. The phase I trial is often the initial step in the clinical
evaluation of a combination regimen. In view of the importance of combination
regimens and the challenges associated with developing them, the Clinical Trial
Design (CTD) Task Force of the National Cancer Institute Investigational Drug
Steering Committee developed a set of recommendations for the phase I development
of a combination regimen. The first two recommendations focus on the scientific
rationale and development plans for the combination regimen; subsequent
recommendations encompass clinical design aspects. The CTD Task Force recommends
that selection of the proposed regimens be based on a biologic or pharmacologic
rationale supported by clinical and/or robust and validated preclinical evidence,
and accompanied by a plan for subsequent development of the combination. The
design of the phase I clinical trial should take into consideration the potential
pharmacokinetic and pharmacodynamic interactions as well as overlapping toxicity.
Depending on the specific hypothesized interaction, the primary endpoint may be
dose optimization, pharmacokinetics, and/or pharmacodynamics (i.e., biomarker).
PMID- 25125264
TI - High variability of atmospheric mercury in the summertime boundary layer through
the central Arctic Ocean.
AB - The biogeochemical cycles of mercury in the Arctic springtime have been
intensively investigated due to mercury being rapidly removed from the
atmosphere. However, the behavior of mercury in the Arctic summertime is still
poorly understood. Here we report the characteristics of total gaseous mercury
(TGM) concentrations through the central Arctic Ocean from July to September,
2012. The TGM concentrations varied considerably (from 0.15 ng/m(3) to 4.58
ng/m(3)), and displayed a normal distribution with an average of 1.23 +/- 0.61
ng/m(3). The highest frequency range was 1.0-1.5 ng/m(3), lower than previously
reported background values in the Northern Hemisphere. Inhomogeneous
distributions were observed over the Arctic Ocean due to the effect of sea ice
melt and/or runoff. A lower level of TGM was found in July than in September,
potentially because ocean emission was outweighed by chemical loss.
PMID- 25125265
TI - Caries experience and use of dental services in rural and urban adults and older
adults from central Chile.
AB - OBJECTIVE: To determine whether there is a relationship between the use of dental
services and caries experience in adults and older adults from central Chile.
MATERIALS AND METHODS: A sample of 453 adults, 35-44 years of age, and 438 older
adults, 65-74 years of age, was interviewed and examined using World Health
Organisation (WHO) methods. Sociodemographic variables were also registered.
Caries experience was assessed using the Decayed, Missing and Filled teeth (DMFT)
index. Multiple linear regression models were used to determine whether there was
an association between the independent variables and caries experience. RESULTS:
Caries prevalence was 99.6% for adults [DMFT score = 14.89 (+/-6.16)] and 99.8%
for older adults [DMFT score = 25.68 (+/-6.49)]. Less than half of the population
- 41.7% of adults and 31.5% of older adults - received dental care. Regardless of
the age group, there were no differences in the DMFT score between those who
received and those who did not receive attention (P > 0.05). When the DMFT
findings were analysed in greater detail, people who received dental care and
urban participants had more fillings (P < 0.05) than did those who were not
provided with attention or lived in rural areas, who, in turn, had more missing
teeth (P < 0.05). A higher educational level was associated with a decrease of
1.15 DMFT points (P = 0.003) in the group of older adults. CONCLUSIONS: Adults
and older adults from the Maule Region showed severe dental damage from caries.
Although rurality and use of services do not seem to affect caries experience,
they are associated with differences in fillings and missing teeth.
PMID- 25125259
TI - Functional kinomics identifies candidate therapeutic targets in head and neck
cancer.
AB - PURPOSE: To identify novel therapeutic drug targets for p53-mutant head and neck
squamous cell carcinoma (HNSCC). EXPERIMENTAL DESIGN: RNAi kinome viability
screens were performed on HNSCC cells, including autologous pairs from primary
tumor and recurrent/metastatic lesions, and in parallel on murine squamous cell
carcinoma (MSCC) cells derived from tumors of inbred mice bearing germline
mutations in Trp53, and p53 regulatory genes: Atm, Prkdc, and p19(Arf). Cross
species analysis of cell lines stratified by p53 mutational status and metastatic
phenotype was used to select 38 kinase targets. Both primary and secondary RNAi
validation assays were performed on additional HNSCC cell lines to credential
these kinase targets using multiple phenotypic endpoints. Kinase targets were
also examined via chemical inhibition using a panel of kinase inhibitors. A
preclinical study was conducted on the WEE1 kinase inhibitor, MK-1775. RESULTS:
Our functional kinomics approach identified novel survival kinases in HNSCC
involved in G2-M cell-cycle checkpoint, SFK, PI3K, and FAK pathways. RNAi
mediated knockdown and chemical inhibition of the WEE1 kinase with a specific
inhibitor, MK-1775, had a significant effect on both viability and apoptosis.
Sensitivity to the MK-1775 kinase inhibitor is in part determined by p53
mutational status, and due to unscheduled mitotic entry. MK-1775 displays single
agent activity and potentiates the efficacy of cisplatin in a p53-mutant HNSCC
xenograft model. CONCLUSIONS: WEE1 kinase is a potential therapeutic drug target
for HNSCC. This study supports the application of a functional kinomics strategy
to identify novel therapeutic targets for cancer.
PMID- 25125263
TI - Lower subcortical gray matter volume in both younger smokers and established
smokers relative to non-smokers.
AB - Although established adult smokers with long histories of nicotine dependence
have lower neural tissue volume than non-smokers, it is not clear if lower
regional brain volume is also observed in younger, less established smokers. The
primary goal of this study was to investigate neural tissue volume in a large
group of smokers and non-smokers, with a secondary goal of measuring the impact
of age on these effects. We used voxel-based morphometry to compare regional gray
matter volume in 118 individuals (59 smokers, 59 age- and gender-matched non
smokers). Younger smokers had significantly lower gray matter volume in the left
thalamus and the left amygdala than their non-smoking peers (family-wise error
corrected clusters, P < 0.05). There was no correlation between smoking use
variables and tissue volume among younger smokers. Established smokers had
significantly lower gray matter volume than age-matched non-smokers in the
insula, parahippocampal gyrus and pallidum. Medial prefrontal cortex gray matter
volume was negatively correlated with pack-years of smoking among the established
smokers, but not the younger smokers. These data reveal that regional tissue
volume differences are not limited exclusively to established smokers. Deficits
in young adults indicate that cigarette smoking may either be deleterious to the
thalamus and amygdala at an earlier age than previously reported, or that pre
existing differences in these areas may predispose individuals to the development
of nicotine dependence.
PMID- 25125266
TI - Chondroprotective effect of high-dose zoledronic acid: An experimental study in a
rabbit model of osteoarthritis.
AB - To address the need to impact the subchondral bone-articular cartilage
interaction for the treatment of degenerative osteoarthritis (OA),
bisphosphonates may be used as a means to inhibit the subchondral bone
resorption. The purpose of the present study is to evaluate the chondroprotective
effect of zoledronic acid (ZOL) in a model of OA. Eighteen adult male rabbits
underwent an anterior cruciate ligament transection and were separated into two
groups: ZOL group (n=10) received 0.6 mg/kg intravenous injection of ZOL on day
1, 15, and 29 and placebo group (n=8) received saline. The animals were
euthanized at 8 weeks. Macroscopically, the ZOL group had significantly milder
ulcerations, cartilage softening and fibrillation compared to the placebo group.
Microscopically, morphology of the articular cartilage was better in the ZOL
treated group compared with the placebo group, without complete disorganization
in any section of the ZOL group. Furthermore, the chondrocytes in the ZOL treated
group were mainly cloning, indicating cartilage repairing and regeneration
process, while in the placebo group hypocellularity predominated. Additionally,
subchondral necrosis was evident in some specimens of the placebo group.
Zoledronic acid, in a high-dose regimen, proved to be chondroprotective in a well
established animal model of OA.
PMID- 25125267
TI - Resurgence: Response competition, stimulus control, and reinforcer control.
AB - Resurgence is the relapse of a previously reinforced and then extinguished target
response when extinguishing a more recently reinforced alternative response. We
designed the present study to assess the contribution of stimulus-control and
reinforcer-control processes in determining resurgence. In a modified resurgence
procedure, we removed the alternative discriminative stimulus signaling
alternative reinforcement when extinguishing the alternative response. This
produced more abrupt resurgence of target responding than in a typical resurgence
procedure maintaining the alternative discriminative stimulus when extinguishing
the alternative response. The overall amount of resurgence did not differ.
Importantly, a "renewal" control added and removed the alternative stimulus
during extinction, identically as in the modified resurgence procedure. However,
alternative responding was never reinforced, which produced no relapse of target
responding. Therefore, the more abrupt resurgence with the modified procedure
than with the typical procedure suggests removing the alternative stimulus
reduced the competition between alternative and target responding. These findings
revealed the importance of adding and removing alternative reinforcement in
producing resurgence (reinforcer control) but little influence of simply adding
and removing the alternative stimulus (stimulus control). These data suggest that
clinicians should consider the long-term availability of the alternative response
option when developing differential-reinforcement interventions.
PMID- 25125268
TI - Chronic fistula after laparoscopic vertical gastrectomy.
PMID- 25125269
TI - Homozygosity for a novel deletion downstream of the SHOX gene provides evidence
for an additional long range regulatory region with a mild phenotypic effect.
AB - Leri-Weill dyschondrosteosis is caused by heterozygous mutations in SHOX or its
flanking sequences, including whole or partial gene deletions, point mutations
within the coding sequence, and deletions of downstream regulatory elements. The
same mutations when biallelic cause the more severe Langer Mesomelic dysplasia.
Here, we report on a consanguineous family with a novel deletion downstream of
SHOX in which homozygously deleted individuals have a phenotype intermediate
between Leri-Weill dyschondrosteosis and Langer Mesomelic dysplasia while
heterozygously deleted individuals are mostly asymptomatic. The deleted region is
distal to all previously described 3' deletions, suggesting the presence of an
additional regulatory element, deletions of which have a milder, variable
phenotypic effect.
PMID- 25125270
TI - Diagnostic value of S100B protein in the differential diagnosis of acute vertigo
in the emergency department.
AB - OBJECTIVES: Vertigo is a common presenting complaint resulting from central or
peripheral etiologies. Because central causes may be life-threatening,
ascertaining the nature of the vertigo is crucial in the emergency department
(ED). With a broad range of potential etiologies, distinguishing central causes
from benign peripheral causes is a diagnostic challenge. Cranial magnetic
resonance imaging (MRI) is the recommended neuroimaging method when clinical
findings are ambiguous. However, MRI scanning for every patient with an uncertain
diagnosis may not be efficient or possible. Therefore, to improve ED resource
utilization for patients with vertigo, there is a need to identify the subset
most likely to have MRI abnormalities. It has previously been shown that S100B
protein provides a useful serum marker of stroke, subarachnoid hemorrhage, and
traumatic brain injury. This study evaluated whether S100B levels could predict
central causes of vertigo as identified by cranial MRI in the ED. METHODS: This
prospective, observational study was conducted with adult patients with acute
onset vertigo (within 6 hours) in the ED of a teaching hospital in Kocaeli,
Turkey. Patients with nausea or dizziness complaints without previously known
vertigo or cranial pathology, and who agreed to participate in the study, were
included. Patients with trauma or with neurologic findings that developed
concurrent with their symptoms were excluded. Serum levels of S100B were measured
with an electrochemiluminescence immunoassay kit. All subjects underwent cranial
MRI. The predictors of positive MRI results were evaluated using logistic
regression analysis. Sensitivity and specificity of S100B levels for identifying
subjects with central causes of vertigo on MRI were calculated with receiver
operating characteristic (ROC) curve. RESULTS: Of the 82 subjects included in the
study, 48 (58.5%) were female, and the mean (+/-SD) age was 51 (+/-16) years.
Thirty-one (37.8%) subjects had positive MRI results. Median (with interquartile
range [IQR]) serum S100B levels were significantly different between MRI-negative
and MRI-positive groups (median = 27.00 pg/mL, IQR = 10.00 to 44.60 vs. median =
60.94 pg/mL, IQR = 38.25 to 77.95, respectively; p = 0.04). In logistic
regression analysis, subjective "he or she is spinning" (p = 0.030, odds ratio
[OR] = 1.63, 95% confidence interval [CI] = 1.38 to 2.49), systolic blood
pressure (sBP; p = 0.045, OR = 1.044, 95% CI = 1.021 to 1.080), and serum S100B
level (p = 0.042, OR = 1.22, 95% CI = 1.018 to 1.445) were found to be
independent predictors of MRI abnormalities. In the ROC analysis, S100B > 30
pg/mL predicted the clinical outcome with 83.9% sensitivity (95% CI = 66.3% to
94.5%) and 51.0% specificity (95% CI = 36.6% to 65.2%). The area under the ROC
curve was 0.774 (95% CI = 0.666 to 0.881). CONCLUSIONS: To the best of our
knowledge this is the first study assessing the utility of serum S100B levels for
diagnosis of acute-onset vertigo. Serum S100B levels are associated with the
presence of central causes of vertigo on cranial MRI. However, serum S100B levels
are not sufficiently sensitive to exclude candidates from cranial MRI.
PMID- 25125273
TI - Go team!
PMID- 25125274
TI - Interprofessional education and collaboration: a call to action for emergency
medicine.
PMID- 25125271
TI - Brief intervention to increase emergency department uptake of combined rapid
human immunodeficiency virus and hepatitis C screening among a drug misusing
population.
AB - OBJECTIVES: In this study, Increasing Viral Testing in the Emergency Department
(InVITED), the authors investigated if a brief intervention about human
immunodeficiency virus (HIV) and hepatitis C virus (HCV) risk-taking behaviors
and drug use and misuse in addition to a self-administered risk assessment,
compared to a self-administered risk assessment alone, increased uptake of
combined screening for HIV and HCV, self-perception of HIV/HCV risk, and impacted
beliefs and opinions on HIV/HCV screening. METHODS: InVITED was a randomized,
controlled trial conducted at two urban emergency departments (EDs) from February
2011 to March 2012. ED patients who self-reported drug use within the past 3
months were invited to enroll. Drug misuse severity and need for a brief or more
intensive intervention was assessed using the Alcohol, Smoking and Substance
Involvement Screening Test (ASSIST). Participants were randomly assigned to one
of two study arms: a self-administered HIV/HCV risk assessment alone (control
arm) or the assessment plus a brief intervention about their drug misuse and
screening for HIV/HCV (intervention arm). Beliefs on the value of combined
HIV/HCV screening, self-perception of HIV/HCV risk, and opinions on HIV/HCV
screening in the ED were measured in both study arms before the HIV/HCV risk
assessment (pre), after the assessment in the control arm, and after the brief
intervention in the intervention arm (post). Participants in both study arms were
offered free combined rapid HIV/HCV screening. Uptake of screening was compared
by study arm. Multivariable logistic regression models were used to evaluate
factors related to uptake of screening. RESULTS: Of the 395 participants in the
study, the median age was 28 years (interquartile range [IQR] = 23 to 38 years),
44.8% were female, 82.3% had ever been tested for HIV, and 67.3% had ever been
tested for HCV. Uptake of combined rapid HIV/HCV screening was nearly identical
by study arm (64.5% vs. 65.2%; Delta = -0.7%; 95% confidence interval [CI] =
10.1% to 8.7%). Of the 256 screened, none had reactive HIV antibody tests, but
seven (2.7%) had reactive HCV antibody tests. Multivariable logistic regression
analysis results indicated that uptake of screening was not related to study arm
assignment, total ASSIST drug scores, need for an intervention for drug misuse,
or HIV/HCV sexual risk assessment scores. However, uptake of screening was
greater among participants who indicated placing a higher value on combined rapid
HIV/HCV screening for themselves and all ED patients and those with higher levels
of perceived HIV/HCV risk. Uptake of combined rapid HIV/HCV screening was not
related to changes in beliefs regarding the value of combined HIV/HCV screening
or self-perceived HIV/HCV risk (post- vs. pre-risk assessment with or without a
brief intervention). Opinions regarding the ED as a venue for combined rapid
HIV/HCV screening were not related to uptake of screening. CONCLUSIONS: Uptake of
combined rapid HIV/HCV screening is high and considered valuable among drug using
and misusing ED patients with little concern about the ED as a screening venue.
The brief intervention investigated in this study does not appear to change
beliefs regarding screening, self-perceived risk, or uptake of screening for
HIV/HCV in this population. Initial beliefs regarding the value of screening and
self-perceived risk for these infections predict uptake of screening.
PMID- 25125272
TI - Emergency physicians' attitudes and preferences regarding computed tomography,
radiation exposure, and imaging decision support.
AB - OBJECTIVES: Although computerized decision support for imaging is often
recommended for optimizing computed tomography (CT) use, no studies have
evaluated emergency physicians' (EPs') preferences regarding computerized
decision support in the emergency department (ED). In this needs assessment, the
authors sought to determine if EPs view overutilization as a problem, if they
want decision support, and if so, the kinds of support they prefer. METHODS: A 42
item, Web-based survey of EPs was developed and used to measure EPs' attitudes,
preferences, and knowledge. Key contacts at local EDs sent letters describing the
study to their physicians. Exploratory principal components analysis (PCA) was
used to determine the underlying factor structure of multi-item scales,
Cronbach's alpha was used to measure internal consistency of items on a scale,
Spearman correlations were used to describe bivariate associations, and
multivariable linear regression analysis was used to identify variables
independently associated with physician interest in decision support. RESULTS: Of
235 surveys sent, 155 (66%) EPs responded. Five factors emerged from the PCA. EPs
felt that: 1) CT overutilization is a problem in the ED (alpha = 0.75); 2) a
patient's cumulative CT study count affects decisions of whether and what type of
imaging study to order only some of the time (alpha = 0.75); 3) knowledge that a
patient has had prior CT imaging for the same indication makes EPs less likely to
order a CT (alpha = 0.42); 4) concerns about malpractice, patient satisfaction,
or insistence on CTs affect CT ordering decisions (alpha = 0.62); and 5) EPs want
decision support before ordering CTs (alpha = 0.85). Performance on knowledge
questions was poor, with only 18% to 39% correctly responding to each of the
three multiple-choice items about effective radiation doses of chest radiograph
and single-pass abdominopelvic CT, as well as estimated increased risk of cancer
from a 10-mSv exposure. Although EPs wanted information on patients' cumulative
exposures, they feel inadequately familiar with this information to make use of
it clinically. If provided with patients' cumulative radiation exposures from CT,
87% of EPs said that they would use this information to discuss imaging options
with their patients. In the multiple regression model, which included all
variables associated with interest in decision support at p < 0.10 in bivariate
tests, items independently associated with EPs' greater interest in all types of
decision support proposed included lower total knowledge scores, greater
frequency that cumulative CT study count affects EP's decision to order CTs, and
greater agreement that overutilization of CT is a problem and that awareness of
multiple prior CTs for a given indication affects CT ordering decisions.
CONCLUSIONS: Emergency physicians view overutilization of CT scans as a problem
with potential for improvement in the ED and would like to have more information
to discuss risks with their patients. EPs are interested in all types of imaging
decision support proposed to help optimize imaging ordering in the ED and to
reduce radiation to their patients. Findings reveal several opportunities that
could potentially affect CT utilization.
PMID- 25125275
TI - Patient safety training in pediatric emergency medicine: a national survey of
program directors.
AB - OBJECTIVES: The Accreditation Council for Graduate Medical Education requires
training in patient safety and medical errors but does not provide specification
for content or methods. Pediatric emergency medicine (EM) fellowship directors
were surveyed to characterize current training of pediatric EM fellows in patient
safety and to determine the need for additional training. METHODS: From June 2013
to August 2013, pediatric EM fellowship directors were surveyed via e-mail.
RESULTS: Of the 71 eligible survey respondents, 57 (80.3%) completed surveys. A
formal curriculum was present in 24.6% of programs, with a median of 6 hours
(range = 1 to 18 hours) dedicated to the curriculum. One program evaluated the
efficacy of the curriculum. Nearly 91% of respondents without formal programs
identified lack of local faculty expertise or interest as the primary barrier to
implementing patient safety curricula. Of programs without formal curricula,
93.6% included at least one component of patient safety training in their
fellowship programs. The majority of respondents would implement a standardized
patient safety curriculum for pediatric EM if one was available. CONCLUSIONS:
Despite the importance of patient safety training and requirements to train
pediatric EM fellows in patient safety and medical errors, there is a lack of
formal curriculum and local faculty expertise. The majority of programs have
introduced components of patient safety training and desire a standardized
curriculum.
PMID- 25125278
TI - Microanatomy of the medial collateral ligament enthesis in the bovine knee.
AB - This study applied transmission and differential interference contrast light
microscopy imaging methodologies to revisit the microanatomy of the ligament-bone
junction of the medial collateral ligament, with the aim of providing new
insights into the mechanostructural significance of the enthesis. The data show
that the microscale structural features of the enthesis are more complex than the
conventional description of "direct versus indirect," or "fibrous versus
nonfibrous" insertions. From a materials perspective the enthesis may be viewed
as a specialised functionally graded structural continuum whose unique microlevel
structural adaptation contributes to maintaining both the local tissue
micromechanical environment and joint function at the macrolevel.
PMID- 25125279
TI - Evaluation of metals, metalloids, and ash mixture toxicity using sediment
toxicity testing.
AB - In December 2008, a release of 4.1 million m(3) of coal ash from the Tennessee
Valley Authority Kingston Fossil Plant occurred. Ash washed into the Emory River
and migrated downstream into the Clinch and Tennessee Rivers. A Baseline
Ecological Risk Assessment evaluated risks to ecological receptors from ash in
the river system post-dredging. This article describes the approach used and
results from sediment toxicity tests, discussing any causal relationships between
ash, metals, and toxicity. Literature is limited in the realm of aquatic coal
combustion residue (CCR) exposures and the potential magnitude of effects on
benthic invertebrates. Sediment samples along a spectrum of ash content were used
in a tiered toxicity testing approach and included a combination of 10 day
sediment toxicity acute tests and longer-term, partial life cycle "definitive"
tests with 2 species (Hyalella azteca and Chironomus dilutus). Arsenic, and to a
lesser extent Se, in the ash was the most likely toxicant causing observed
effects in the laboratory toxicity tests. Sites in the Emory River with the
greatest statistical and biologically significant effects had As concentrations
in sediments twice the probable effects concentration of 33 mg/kg. These sites
contained greater than 50% ash. Sites with less than approximately 50% ash in
sediments exhibited fewer significant toxic responses relative to the reference
sediment in the laboratory. The results discussed here present useful evidence of
only limited effects occurring from a worst-case exposure pathway. These results
provided a valuable line of evidence for the overall assessment of risks to
benthic invertebrates and to other ecological receptors, and were crucial to risk
management and development of project remediation goals.
PMID- 25125281
TI - Young slow-progressing ALS patients are at higher risk of inappropriate and
disease-quickening surgeries.
PMID- 25125280
TI - Anatomical structure and ultrastructure of the endocarp cell walls of Argania
spinosa (L.) Skeels (Sapotaceae).
AB - The anatomical and histochemical study of young and adult endocarps of Argania
spinosa (sampled from Tindouf; Algeria) shows a general structure that is similar
to that of majority of stone fruits. These samples consist of tissues that
contain lignified and cellulosic cell walls. The majority of the tissues are
composed of sclerenchyma cells; with very thick lignified cell walls and
conducting tissues. Coniferyl lignins are abundant in the majority of the
lignified tissues. However, the coniferyl lignins appear at the primary xylem
during lignification. Syringyl lignins are present in small quantities. The
electron microscopy observation of the sclerenchyma cell walls of the young
endocarp shows polylamellate strates and, cellular microfibrils in arced
patterns. This architecture is observed in the cell walls of the adult endocarp
only after the incubation of the tissue in methylamine. These configurations
(arcs) are the result of a regular and complete rotation with a 180 degrees
variation in the microfibril angle; the complete and symmetrical arcs show a
helicoidal mode of construction. The observation of the sclerenchyma cells
revealed the capacity of helicoidal morphogenesis to adjust itself under the
influence of topological constraints, such as the presence of a large number of
pit canals, which maintain symplastic transport.
PMID- 25125282
TI - Biogeography and speciation of terrestrial fauna in the south-western Australian
biodiversity hotspot.
AB - The south-western land division of Western Australia (SWWA), bordering the
temperate Southern and Indian Oceans, is the only global biodiversity hotspot
recognised in Australia. Renowned for its extraordinary diversity of endemic
plants, and for some of the largest and most botanically significant temperate
heathlands and woodlands on Earth, SWWA has long fascinated biogeographers. Its
flat, highly weathered topography and the apparent absence of major geographic
factors usually implicated in biotic diversification have challenged attempts to
explain patterns of biogeography and mechanisms of speciation in the region.
Botanical studies have always been central to understanding the biodiversity
values of SWWA, although surprisingly few quantitative botanical analyses have
allowed for an understanding of historical biogeographic processes in both space
and time. Faunistic studies, by contrast, have played little or no role in
defining hotspot concepts, despite several decades of accumulating quantitative
research on the phylogeny and phylogeography of multiple lineages. In this review
we critically analyse datasets with explicit supporting phylogenetic data and
estimates of the time since divergence for all available elements of the
terrestrial fauna, and compare these datasets to those available for plants. In
situ speciation has played more of a role in shaping the south-western Australian
fauna than has long been supposed, and has occurred in numerous endemic lineages
of freshwater fish, frogs, reptiles, snails and less-vagile arthropods. By
contrast, relatively low levels of endemism are found in birds, mammals and
highly dispersive insects, and in situ speciation has played a negligible role in
generating local endemism in birds and mammals. Quantitative studies provide
evidence for at least four mechanisms driving patterns of endemism in south
western Australian animals, including: (i) relictualism of ancient Gondwanan or
Pangaean taxa in the High Rainfall Province; (ii) vicariant isolation of lineages
west of the Nullarbor divide; (iii) in situ speciation; and (iv) recent
population subdivision. From dated quantitative studies we derive four testable
models of historical biogeography for animal taxa in SWWA, each explicit in
providing a spatial, temporal and topological perspective on patterns of
speciation or divergence. For each model we also propose candidate lineages that
may be worthy of further study, given what we know of their taxonomy,
distributions or relationships. These models formalise four of the strongest
patterns seen in many animal taxa from SWWA, although other models are clearly
required to explain particular, idiosyncratic patterns. Generating numerous new
datasets for suites of co-occurring lineages in SWWA will help refine our
understanding of the historical biogeography of the region, highlight gaps in our
knowledge, and allow us to derive general postulates from quantitative (rather
than qualitative) results. For animals, this process has now begun in earnest, as
has the process of taxonomically documenting many of the more diverse
invertebrate lineages. The latter remains central to any attempt to appreciate
holistically biogeographic patterns and processes in SWWA, and molecular
phylogenetic studies should - where possible - also lead to tangible taxonomic
outcomes.
PMID- 25125283
TI - Trisphosphine-chelate-substituted molybdenum and tungsten nitrosyl hydrides as
highly active catalysts for olefin hydrogenations.
AB - Reaction of [M(NO)Cl3 (NCMe)2 ] (M=Mo, W) with (iPr2 PCH2 CH2 )2 PPh (etp(i) p)
at room temperature afforded the syn/anti-[M(NO)Cl3 (mer-etp(i) p)] complexes
(M=Mo, a; W, b; 3 a,b(syn,anti); syn and anti refer to the relative position of
Ph(etp(i) p) and NO). Reduction of 3 a,b(syn,anti) produced [M(NO)Cl2 (mer-etp(i)
p)] (4 a,b(syn)), [M(NO)Cl(NCMe)(mer-etp(i) p)] (5 a,b(syn,anti)), and
[M(NO)Cl(eta(2) -ethylene)(mer-etp(i) p)] (6 a,b(syn,anti)) complexes. The
hydrides [M(NO)H(eta(2) -ethylene)(mer-etp(i) p)] (7 a,b(syn,anti)) were obtained
from 6 a,b(syn,anti) using NaHBEt3 (75 degrees C, THF) or LiBH4 (80 degrees C,
Et3 N), respectively. 7 a,b(syn,anti) were probed in olefin hydrogenations in the
absence or presence of a hydrosilane/B(C6 F5 )3 mixture. The 7 a,b(syn,anti)/Et3
SiH/B(C6 F5 )3 co-catalytic systems were highly active in various olefin
hydrogenations (60 bar H2 , 140 degrees C), with maximum TOFs of 5250 h(-1) (7
a(syn,anti)) and 8200 h(-1) (7 b(syn,anti)) for 1-hexene hydrogenation. The Et3
SiH/(B(C6 F5 )3 co-catalyst is anticipated to generate a [Et3 Si](+) cation
attaching to the ONO atom. This facilitates NO bending and accelerates catalysis
by providing a vacant site. Inverse DKIE effects were observed for the 7
a(syn,anti)/Et3 SiH/(B(C6 F5 )3 (kH /kD =0.55) and the 7 b(syn,anti)/Et3
SiH/(B(C6 F5 )3 (kH /kD =0.65) co-catalytic mixtures (20 bar H2 /D2 , 140
degrees C).
PMID- 25125284
TI - Postnatal depression.
PMID- 25125285
TI - ALien Biotic IndEX (ALEX) - a new index for assessing impacts of alien species on
benthic communities.
AB - Biotic indices are mainly aimed at assessing levels of deterioration caused by
chemical or organic pollution. However, no biotic index to date has been
developed to detect impacts of alien species on benthic communities. In this
paper, a new biotic index, namely ALEX, is proposed to address the objectives of
the Water Framework Directive and was tested in Mersin Bay (Levantine Sea,
Turkey). Species were divided into four biogeographic groups, namely native
species, casual species, established species and invasive species, and the metric
considers the relative importance of these groups in samples. The index
classified the ecological status of some stations which are shallow, and close to
harbor and river mouths as bad or poor in February and October. The ALEX values
were positively and significantly correlated with total nitrogen, silicate and
silt percentage in sediment, and negatively correlated with depth and the
distance from the harbor.
PMID- 25125286
TI - Simulation of the potential effects of CO2 leakage from carbon capture and
storage activities on the mobilization and speciation of metals.
AB - One of the main risks associated with carbon capture and storage (CCS) activities
is the leakage of the stored CO2, which can result in several effects on the
ecosystem. Laboratory-scale experiments were performed to provide data on the
possible effects of CO2 leakage from CCS on the mobility of metals previously
trapped in sediments. Metal-contaminated sediments were collected and submitted
to acidification by means of CO2 injection using different pH treatments. The
test lasted 10 days, and samples were collected at the beginning and at the end
of the experiment for metal analysis. The results revealed increases in the
mobility of metals such as Co, Cu, Fe, Pb and Zn due to pH decreases. Geochemical
modeling demonstrated that acidification influenced the speciation of the metals,
increasing the concentrations of their free forms. These data suggest the
possible sediment contamination consequences of accidental CO2 leakage during CCS
activities.
PMID- 25125287
TI - Marine litter ensemble transport simulations in the southern North Sea.
AB - The drift of marine litter in the southern North Sea was simulated with the
offline Lagrangian transport model PELETS-2D. Assuming different source regions,
passive tracer particles were released every 28 h within a nine-year period.
Based on pre-calculated hourly wind and ocean current data, drift simulations
were carried out forward and backward in time with and without the assumption of
extra wind forces influencing particle movement. Due to strong variability of
currents, backward simulations did not allow for the identification of particular
source regions influencing given monitoring sites. Neither accumulation regions
at open sea could be identified by forward simulations. A seasonal signal,
however, could be identified in the number of tracer particles that reached the
coastal areas. Both particle drift velocity and variability of drift paths
further increased when an extra wind drift was assumed.
PMID- 25125288
TI - Rapid, repeated, low-dose challenges with SIVmac239 infect animals in a condensed
challenge window.
AB - BACKGROUND: Simian immunodeficiency virus (SIV) infection of nonhuman primates is
the predominant model for preclinical evaluation of human immunodeficiency virus
(HIV) vaccines. These studies frequently utilize high-doses of SIV that ensure
infection after a single challenge but do not recapitulate critical facets of
sexual HIV transmission. Investigators are increasingly using low-dose challenges
in which animals are challenged once every week or every two weeks in order to
better replicate sexual HIV transmission. Using this protocol, some animals
require over ten challenges before SIV infection is detectable, potentially
inducing localized immunity. Moreover, the lack of certainty over which challenge
will lead to productive infection prevents tissue sampling immediately
surrounding the time of infection. FINDINGS: Here we challenged Mauritian
cynomolgus macaques with 100 50% tissue culture infectious doses (TCID50) of
SIVmac239 intrarectally three times a day for three consecutive days. Ten of
twelve animals had positive plasma viral loads after this challenge regimen.
CONCLUSIONS: This approach represents a straightforward advance in SIV challenge
protocols that may avoid induction of local immunity, avoid inconsistent timing
between last immunization and infection, and allow sampling immediately after
infection using low-dose challenge protocols.
PMID- 25125289
TI - Local vasotocin modulation of the pacemaker nucleus resembles distinct electric
behaviors in two species of weakly electric fish.
AB - The neural bases of social behavior diversity in vertebrates have evolved in
close association with hypothalamic neuropeptides. In particular, arginine
vasotocin (AVT) is a key integrator underlying differences in behavior across
vertebrate taxa. Behavioral displays in weakly electric fish are channeled
through specific patterns in their electric organ discharges (EODs), whose rate
is ultimately controlled by a medullary pacemaker nucleus (PN). We first explored
interspecific differences in the role of AVT as modulator of electric behavior in
terms of EOD rate between the solitary Gymnotus omarorum and the gregarious
Brachyhypopomus gauderio. In both species, AVT IP injection (10MUg/gbw) caused a
progressive increase of EOD rate of about 30%, which was persistent in B.
gauderio, and attenuated after 30min in G. omarorum. Secondly, we demonstrated by
in vitro electrophysiological experiments that these behavioral differences can
be accounted by dissimilar effects of AVT upon the PN in itself. AVT
administration (1MUM) to the perfusion bath of brainstem slices containing the PN
produced a small and transient increase of PN activity rate in G. omarorum vs the
larger and persistent increase previously reported in B. gauderio. We also
identified AVT neurons, for the first time in electric fish, using
immunohistochemistry techniques and confirmed the presence of hindbrain AVT
projections close to the PN that might constitute the anatomical substrate for
AVT influences on PN activity. Taken together, our data reinforce the view of the
PN as an extremely plastic medullary central pattern generator that not only
responds to higher influences to adapt its function to diverse contexts, but also
is able to intrinsically shape its response to neuropeptide actions, thus adding
a hindbrain target level to the complexity of the global integration of central
neuromodulation of electric behavior.
PMID- 25125291
TI - Blood volume measurement by hemodilution: association with valve disease and re
evaluation of the Allen Formula.
AB - BACKGROUND: Total blood volume (TBV) assessment is central to the management of
cardiac surgical patients with cardiopulmonary bypass (CPB). The widely accepted
Allen Formula lacks accuracy in estimating TBV in these patients. Moreover, the
impact of commonly encountered cardiac disease states on TBV has not been
systematically investigated. The aim of this study was to determine TBV by
hemodilution (TBVHD) for patients with valve disease, compare TBVHD to algorithms
frequently used during cardiac surgery and to modify the Allen Formula to better
fit today's patient population. METHODS: TBVHD was prospectively measured upon
initiation of CPB. Ninety-six patients were grouped into 4 cohorts by
preoperative diagnosis and compared to Allen and weight-based formulae in a
univariate analysis: mitral regurgitation (MR), coronary artery disease requiring
bypass surgery (CABG) and aortic stenosis (AS) +/- CABG. The independent effects
of height and weight on TBV were correlated to the original Allen Formula by
multiple linear regression. RESULTS: Patients with MR had significantly larger
TBVHD compared to patients with AS, CABG or both. The smallest TBVHD was found in
the patients with AS and CABG. The modified Allen Formula had an excellent model
fit (R(2) = 0.88 and R(2) = 0.95 for males and females, respectively; p<0.001)
while the classic formula overestimated TBV by 30% in males and females. For
males, height impacted TBV calculations the most whereas weight was the
predominant determinant in females. CONCLUSION: Blood volume assessment via the
Allen Formula or bodyweight overestimated TBV in cardiac surgical patients, with
potential implications on their management. The assumption that MR frequently
presents with increased intravascular volume was confirmed whereas AS patients
with coronary disease had a relatively smaller TBV. Lastly, a modified Allen
Formula to better reflect today's patient population was derived to reproducibly
improve accuracy in mathematical estimates of TBV.
PMID- 25125292
TI - Anatomic assessment of sympathetic peri-arterial renal nerves in man.
AB - BACKGROUND: Although renal sympathetic denervation therapy has shown promising
results in patients with resistant hypertension, the human anatomy of peri
arterial renal nerves is poorly understood. OBJECTIVES: The aim of our study was
to investigate the anatomic distribution of peri-arterial sympathetic nerves
around human renal arteries. METHODS: Bilateral renal arteries were collected
from human autopsy subjects, and peri-arterial renal nerve anatomy was examined
by using morphometric software. The ratio of afferent to efferent nerve fibers
was investigated by dual immunofluorescence staining using antibodies targeted
for anti-tyrosine hydroxylase and anti-calcitonin gene-related peptide. RESULTS:
A total of 10,329 nerves were identified from 20 (12 hypertensive and 8
nonhypertensive) patients. The mean individual number of nerves in the proximal
and middle segments was similar (39.6 +/- 16.7 per section and 39.9 +/- 1 3.9 per
section), whereas the distal segment showed fewer nerves (33.6 +/- 13.1 per
section) (p = 0.01). Mean subject-specific nerve distance to arterial lumen was
greatest in proximal segments (3.40 +/- 0.78 mm), followed by middle segments
(3.10 +/- 0.69 mm), and least in distal segments (2.60 +/- 0.77 mm) (p < 0.001).
The mean number of nerves in the ventral region (11.0 +/- 3.5 per section) was
greater compared with the dorsal region (6.2 +/- 3.0 per section) (p < 0.001).
Efferent nerve fibers were predominant (tyrosine hydroxylase/calcitonin gene
related peptide ratio 25.1 +/- 33.4; p < 0.0001). Nerve anatomy in hypertensive
patients was not considerably different compared with nonhypertensive patients.
CONCLUSIONS: The density of peri-arterial renal sympathetic nerve fibers is lower
in distal segments and dorsal locations. There is a clear predominance of
efferent nerve fibers, with decreasing prevalence of afferent nerves from
proximal to distal peri-arterial and renal parenchyma. Understanding these
anatomic patterns is important for refinement of renal denervation procedures.
PMID- 25125290
TI - Efficient and cost effective production of active-form human PKB using silkworm
larvae.
AB - Protein kinase B (PKB) also known as Akt is involved in many signal transduction
pathways. As alterations of the PKB pathway are found in a number of human
malignancies, PKB is considered an important drug target for cancer therapy.
However, production of sufficient amounts of active PKB for biochemical and
structural studies is very costly because of the necessity of using a higher
organism expression system to obtain phosphorylated PKB. Here, we report
efficient production of active PKBalpha using the BmNPV bacmid expression system
with silkworm larvae. Following direct injection of bacmid DNA, recombinant
PKBalpha protein was highly expressed in the fat bodies of larvae, and could be
purified using a GST-tag and then cleaved. A final yield of approximately 1 mg
PKBalpha/20 larvae was recorded. Kinase assays showed that the recombinant
PKBalpha possessed high phosphorylation activity. We further confirmed
phosphorylation on the activation loop by mass spectrometric analysis. Our
results indicate that the silkworm expression system is of value for preparation
of active-form PKBalpha with phosphorylation on the activation loop. This
efficient production of the active protein will facilitate further biochemical
and structural studies and stimulate subsequent drug development.
PMID- 25125293
TI - Catheter-based renal denervation is no simple matter: lessons to be learned from
our anatomy?
PMID- 25125294
TI - Paroxysmal AF catheter ablation with a contact force sensing catheter: results of
the prospective, multicenter SMART-AF trial.
AB - BACKGROUND: Catheter ablation is important for treatment of paroxysmal atrial
fibrillation (PAF). Limited animal and human studies suggest a correlation
between electrode-tissue contact and radiofrequency lesion generation.
OBJECTIVES: The study sought to assess the safety and effectiveness of an
irrigated, contact force (CF)-sensing catheter in the treatment of drug
refractory symptomatic PAF. METHODS: A prospective, multicenter, nonrandomized
study was conducted. Enrollment criteria included: >=3 symptomatic episodes of
PAF within 6 months of enrollment and failure of >=1 antiarrhythmic drug (Class I
to IV). Ablation included pulmonary vein isolation with confirmed entrance block
as procedural endpoint. RESULTS: A total of 172 patients were enrolled at 21
sites, where 161 patients had a study catheter inserted and 160 patients
underwent radiofrequency application. Procedural-related serious adverse events
occurring within 7 days of the procedure included tamponade (n = 4), pericarditis
(n = 3), heart block (n = 1, prior to radiofrequency application), and vascular
access complications (n = 4). By Kaplan-Meier analyses, 12-month freedom from
atrial fibrillation/atrial flutter/atrial tachycardia recurrence was 72.5%. The
average CF per procedure was 17.9 +/- 9.4 g. When the CF employed was between
investigator selected working ranges >=80% of the time during therapy, outcomes
were 4.25 times more likely to be successful (p = 0.0054; 95% confidence
interval: 1.53 to 11.79). CONCLUSIONS: The SMART-AF trial demonstrated that this
irrigated CF-sensing catheter is safe and effective for the treatment of drug
refractory symptomatic PAF, with no unanticipated device-related adverse events.
The increased percent of time within investigator-targeted CF ranges correlates
with increased freedom from arrhythmia recurrence. Stable CF during
radiofrequency application increases the likelihood of 12-month success.
(THERMOCOOL(r) SMARTTOUCH(r) Catheter for Treatment of Symptomatic Paroxysmal
Atrial Fibrillation; NCT01385202).
PMID- 25125295
TI - When it comes to radiofrequency catheter ablation of atrial fibrillation, have
all of our wishes been granted? A perspective on the SMART-AF trial.
PMID- 25125297
TI - Outcomes with digoxin in atrial fibrillation: more data, no answers.
PMID- 25125296
TI - Increased mortality associated with digoxin in contemporary patients with atrial
fibrillation: findings from the TREAT-AF study.
AB - BACKGROUND: Despite endorsement of digoxin in clinical practice guidelines, there
exist limited data on its safety in atrial fibrillation/flutter (AF). OBJECTIVES:
The goal of this study was to evaluate the association of digoxin with mortality
in AF. METHODS: Using complete data of the TREAT-AF (The Retrospective Evaluation
and Assessment of Therapies in AF) study from the U.S. Department of Veterans
Affairs (VA) healthcare system, we identified patients with newly diagnosed,
nonvalvular AF seen within 90 days in an outpatient setting between VA fiscal
years 2004 and 2008. We used multivariate and propensity-matched Cox proportional
hazards to evaluate the association of digoxin use with death. Residual
confounding was assessed by sensitivity analysis. RESULTS: Of 122,465 patients
with 353,168 person-years of follow-up (age 72.1 +/- 10.3 years, 98.4% male),
28,679 (23.4%) patients received digoxin. Cumulative mortality rates were higher
for digoxin-treated patients than for untreated patients (95 vs. 67 per 1,000
person-years; p < 0.001). Digoxin use was independently associated with mortality
after multivariate adjustment (hazard ratio [HR]: 1.26, 95% confidence interval
[CI]: 1.23 to 1.29, p < 0.001) and propensity matching (HR: 1.21, 95% CI: 1.17 to
1.25, p < 0.001), even after adjustment for drug adherence. The risk of death was
not modified by age, sex, heart failure, kidney function, or concomitant use of
beta-blockers, amiodarone, or warfarin. CONCLUSIONS: Digoxin was associated with
increased risk of death in patients with newly diagnosed AF, independent of drug
adherence, kidney function, cardiovascular comorbidities, and concomitant
therapies. These findings challenge current cardiovascular society
recommendations on use of digoxin in AF.
PMID- 25125298
TI - Prevalence and characteristics of TCFA and degree of coronary artery stenosis: an
OCT, IVUS, and angiographic study.
AB - BACKGROUND: The relationship between features of vulnerable plaque and
angiographic coronary stenosis is unknown. OBJECTIVES: The purpose of this study
was to systematically investigate the absolute number, relative prevalence, and
characteristics of thin-cap fibroatheroma (TCFA) at different degrees of stenosis
using optical coherence tomography (OCT), intravascular ultrasound, and coronary
angiography. METHODS: We identified 643 plaques from 255 subjects who underwent
OCT imaging in all 3 coronary arteries. They were divided into 3 groups on the
basis of angiographic diameter stenosis: Group A (30% to 49%, n = 325), Group B
(50% to 69%, n = 227), and Group C (>70%, n = 91). RESULTS: OCT showed that the
absolute number of TCFA was greatest in Group A (n = 58), followed by Groups B (n
= 40) and C (n = 33). However, the relative prevalence of TCFA was higher in
Group C (36%) than in Groups A (18%) or B (18%) (p = 0.003 and p = 0.002,
respectively). Fibrous cap of TCFA was thinner in Group C than in Groups A (p <
0.001) or B (p = 0.001). intravascular ultrasound showed that the plaque burden
of TCFA was largest in Group C (80.1 +/- 7.4%), compared with Groups B (67.5 +/-
9.4%) and A (58.1 +/- 8.4%). TCFA in Group C had a higher remodeling index than
those in Group A (p = 0.002). CONCLUSIONS: The absolute number of TCFA is 3 times
greater in nonsevere stenosis than in severe stenosis. It is, however, twice as
likely for a lesion to be TCFA in cases of severe stenosis than in nonsevere
stenosis. Moreover, TCFA in severely-stenotic areas had more features of plaque
vulnerability.
PMID- 25125299
TI - Putting TCFA in clinical perspective.
PMID- 25125301
TI - The Fermi paradox and coronary artery disease.
PMID- 25125300
TI - High-risk plaque detected on coronary CT angiography predicts acute coronary
syndromes independent of significant stenosis in acute chest pain: results from
the ROMICAT-II trial.
AB - BACKGROUND: It is not known whether high-risk plaque, as detected by coronary
computed tomography angiography (CTA), permits improved early diagnosis of acute
coronary syndromes (ACS) independently to the presence of significant coronary
artery disease (CAD) in patients with acute chest pain. OBJECTIVES: The primary
aim of this study was to determine whether high-risk plaque features, as detected
by CTA in the emergency department (ED), may improve diagnostic certainty of ACS
independently and incrementally to the presence of significant CAD and clinical
risk assessment in patients with acute chest pain but without objective evidence
of myocardial ischemia or myocardial infarction (MI). METHODS: We included
patients randomized to the coronary CTA arm of the ROMICAT-II (Rule Out
Myocardial Infarction/Ischemia Using Computer-Assisted Tomography II) trial.
Readers assessed coronary CTA qualitatively for the presence of nonobstructive
CAD (1% to 49% stenosis), significant CAD (>=50% or >=70% stenosis), and the
presence of at least 1 of the high-risk plaque features (positive remodeling, low
<30 Hounsfield units plaque, napkin-ring sign, spotty calcium). In logistic
regression analysis, we determined the association of high-risk plaque with ACS
(MI or unstable angina pectoris) during the index hospitalization and whether
this was independent of significant CAD and clinical risk assessment. RESULTS:
Overall, 37 of 472 patients who underwent coronary CTA with diagnostic image
quality (mean age 53.9 +/- 8.0 years; 52.8% men) had ACS (7.8%; MI n = 5;
unstable angina pectoris n = 32). CAD was present in 262 patients (55.5%;
nonobstructive CAD in 217 patients [46.0%] and significant CAD with >=50%
stenosis in 45 patients [9.5%]). High-risk plaques were more frequent in patients
with ACS and remained a significant predictor of ACS (odds ratio [OR]: 8.9; 95%
CI: 1.8 to 43.3; p = 0.006) after adjustment for >=50% stenosis (OR: 38.6; 95%
CI: 14.2 to 104.7; p < 0.001) and clinical risk assessment (age, sex, number of
cardiovascular risk factors). Similar results were observed after adjustment for
>=70% stenosis. CONCLUSIONS: In patients presenting to the ED with acute chest
pain but negative initial electrocardiogram and troponin, presence of high-risk
plaques on coronary CTA increased the likelihood of ACS independent of
significant CAD and clinical risk assessment (age, sex, and number of
cardiovascular risk factors). (Multicenter Study to Rule Out Myocardial
Infarction by Cardiac Computed Tomography [ROMICAT-II]; NCT01084239).
PMID- 25125303
TI - Glycogen synthase kinase-3 and the heart.
PMID- 25125302
TI - Cardiomyocyte-specific deletion of Gsk3alpha mitigates post-myocardial infarction
remodeling, contractile dysfunction, and heart failure.
AB - BACKGROUND: Injury due to myocardial infarction (MI) is largely irreversible.
Once an infarct has occurred, the clinical goal becomes limiting remodeling,
preserving left ventricular function, and preventing heart failure. Although
traditional approaches (e.g., beta-blockers) partially preserve left ventricular
function, novel strategies are needed to limit ventricular remodeling post-MI.
OBJECTIVES: The aim of this study was to determine the role of glycogen synthase
kinase-3alpha (GSK-3alpha) in post-MI remodeling. METHODS: Mice with
cardiomyocyte-specific conditional deletion of Gsk3alpha and littermate controls
underwent sham or MI surgery. Heart function was assessed using serial M-mode
echocardiography. RESULTS: Gsk3alpha deletion in the heart markedly limits
remodeling and preserves left ventricular function post-MI. This is due at least
in part to dramatic thinning and expansion of the scar in the control hearts,
which was less in the heart of knockout (KO) mice. In contrast, the border zone
in the KO mice demonstrated a much thicker scar, and there were more viable
cardiomyocytes within the scar/border zone. This was associated with less
apoptosis and more proliferation of cardiomyocytes in the KO mice.
Mechanistically, reduced apoptosis was due, at least in part, to a marked
decrease in the Bax/Bcl-2 ratio, and increased cardiomyocyte proliferation was
mediated through cyclin E1 and E2F-1 in the hearts of the KO mice. CONCLUSIONS:
Taken together, these findings show that reducing GSK-3alpha expression in
cardiomyocytes limits ventricular remodeling and preserves cardiac function post
MI. Specifically targeting GSK-3alpha could be a novel strategy to limit adverse
remodeling and heart failure.
PMID- 25125305
TI - Carotid artery stenting.
AB - Carotid artery stenting (CAS) has achieved clinical equipoise with carotid
endarterectomy (CEA), as evidenced by 2 large U.S. randomized clinical trials,
multiple pivotal registry trials, and 2 multispecialty guideline documents
endorsed by 14 professional societies. The largest randomized trial conducted in
patients at average surgical risk of CEA, CREST (Carotid Revascularization
Endarterectomy Versus Stenting Trial) found no difference between CAS and CEA for
the combined endpoint of stroke, death, and myocardial infarction (MI) after 4
years of follow-up. The largest randomized trial comparing CAS and CEA in
patients at increased surgical risk, SAPPHIRE (Stenting and Angioplasty with
Protection in Patients at High Risk for Endarterectomy), looked at 1-year stroke,
death, and MI incidence and found no difference in symptomatic patients, but a
significantly better outcome in asymptomatic patients for CAS (9.9% vs. 21.5%; p
= 0.02). Given that >70% of carotid revascularization procedures are performed in
asymptomatic patients for primary prevention of stroke, it is incumbent upon
clinicians to demonstrate that revascularization has an incremental benefit over
highly effective modern medical therapy alone.
PMID- 25125304
TI - Rhythm control in heart failure patients with atrial fibrillation: contemporary
challenges including the role of ablation.
AB - Because nonpharmacological interventions likely alter the risks and benefits
associated with rhythm control, this paper reviews the role of current rhythm
control strategies in atrial fibrillation. This report also focuses on the
specific limitations of pharmacological interventions and the utility of
percutaneous ablation in this growing population of patients with concomitant
atrial fibrillation and heart failure.
PMID- 25125306
TI - Revolutionizing cardiology and health care: a shared purpose makes all the
difference.
PMID- 25125307
TI - Pregnancy in fellowship: building a career and family.
PMID- 25125308
TI - Urinary hyaluronic acid as an early predictor of acute kidney injury after
cardiac surgery.
PMID- 25125309
TI - Would a modified Lewis index be more specific, without marked reduction of
sensitivity, in ECG diagnosis of RVH?
PMID- 25125310
TI - Reply: would a modified Lewis index be more specific, without marked reduction of
sensitivity, in ECG diagnosis of RVH?
PMID- 25125311
TI - A commentary on the SPARC study.
PMID- 25125312
TI - Coronary CT angiography again results in better patient outcomes.
PMID- 25125313
TI - Reply: a commentary on the SPARC study.
PMID- 25125314
TI - Recovery of left ventricular mechanics after transcatheter aortic valve
implantation: effects of baseline ventricular function and postprocedural aortic
regurgitation.
AB - BACKGROUND: Impaired left ventricular (LV) myocardial deformation is associated
with adverse outcome in patients with severe aortic stenosis (AS). The aim of
this retrospective study was to assess the impact of transcatheter aortic valve
implantation (TAVI) on the recovery of myocardial mechanics and the influence of
postprocedural aortic regurgitation (AR). METHODS: Speckle-tracking
echocardiography was used to assess multidirectional myocardial deformation
(longitudinal and circumferential strain) and rotational mechanics (apical
rotation and twist) before and at midterm follow-up after TAVI. Predictors of
myocardial recovery, defined as a >=20% relative increase in the magnitude of
global longitudinal strain compared with baseline, were examined. RESULTS: Sixty
four patients (median age, 83 years; interquartile range, 77-86 years) with
severe AS and high surgical risk (mean European System for Cardiac Operative Risk
Evaluation score, 20 +/- 13%) were evaluated. Overall, LV longitudinal
deformation was impaired at baseline compared with controls. At 5 +/- 3 months
after TAVI, LV longitudinal deformation had significantly improved only in the
group of patients with baseline LV ejection fractions (LVEF) <= 55%: global
longitudinal strain from -9.7 +/- 3.7% to -11.8 +/- 3.2% (P = .05), longitudinal
strain rate from -0.44 +/- 0.14 sec(-1) to -0.57 +/- 0.16 sec(-1) (P = .001), and
early diastolic strain rate from 0.38 +/- 0.17 sec(-1) to 0.49 +/- 0.18 sec(-1)
(P = .01). In patients with normal LVEFs, LV twist was supraphysiologic at
baseline and normalized after TAVI (from 16.1 +/- 6.9 degrees to 11.9 +/- 6.2
degrees , P = .004). In patients with baseline LVEFs <= 55%, circumferential
deformation was impaired before TAVI and improved after TAVI. Baseline LVEF (odds
ratio, 0.56 per 10% increment; P = .02) and global longitudinal strain (odds
ratio, 0.65 per absolute 1% increment; P < .001) were significant predictors of
myocardial recovery. LV mass, volumes, and longitudinal strain failed to
favorably remodel in patients with post-TAVI important AR (defined as new mild
post-TAVI AR or moderate or severe post-TAVI AR [either preexisting or new AR]).
CONCLUSIONS: TAVI restores LV function toward more physiologic myocardial
mechanics in both normal- and depressed-LVEF groups. Patients with lower systolic
function derive the most benefit in terms of longitudinal reverse remodeling.
Postprocedural AR adversely affects LV structural and functional remodeling.
PMID- 25125315
TI - The human meniscus: a review of anatomy, function, injury, and advances in
treatment.
AB - Meniscal injuries are recognized as a cause of significant musculoskeletal
morbidity. The menisci are vital for the normal function and long-term health of
the knee joint. The purpose of this review is to provide current knowledge
regarding the anatomy and biomechanical functions of the menisci, incidence,
injury patterns and the advancements in treatment options of meniscal injury. A
literature search was performed by a review of PubMed, Google Scholar, MEDLINE,
and OVID for all relevant articles published between 1897 and 2014. This study
highlights the anatomical and biomechanical characteristics of the menisci, which
may be relevant to injury patterns and treatment options. An understanding of the
normal anatomy and biomechanical functions of the knee menisci is a necessary
prerequisite to understanding pathologies associated with the knee.
PMID- 25125316
TI - Endophthalmitis prophylaxis for cataract surgery: are intracameral antibiotics
necessary?
PMID- 25125317
TI - Interventions to reduce haemorrhage during myomectomy for fibroids.
AB - BACKGROUND: Benign smooth muscle tumours of the uterus, known as fibroids or
myomas, are often symptomless. However, about one-third of women with fibroids
will present with symptoms that are severe enough to warrant treatment. The
standard treatment of symptomatic fibroids is hysterectomy (that is surgical
removal of the uterus) for women who have completed childbearing, and myomectomy
for women who desire future childbearing or simply want to preserve their uterus.
Myomectomy, the surgical removal of myomas, can be associated with life
threatening bleeding. Excessive bleeding can necessitate emergency blood
transfusion. Knowledge of the effectiveness of the interventions to reduce
bleeding during myomectomy is essential to enable evidence-based clinical
decisions. This is an update of the review published in The Cochrane Library
(2011, Issue 11). OBJECTIVES: To assess the effectiveness, safety, tolerability
and costs of interventions to reduce blood loss during myomectomy. SEARCH
METHODS: In June 2014, we conducted electronic searches in the Cochrane Menstrual
Disorders and Subfertility Group Specialised Register, the Cochrane Central
Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO,
and trial registers for ongoing and registered trials. SELECTION CRITERIA: We
selected randomised controlled trials (RCTs) that compared potential
interventions to reduce blood loss during myomectomy to placebo or no treatment.
DATA COLLECTION AND ANALYSIS: The two authors independently selected RCTs for
inclusion, assessed the risk of bias and extracted data from the included RCTs.
The primary review outcomes were blood loss and need for blood transfusion. We
expressed study results as mean differences (MD) for continuous data and odds
ratios for dichotomous data, with 95% confidence intervals (CI). We assessed the
quality of evidence using GRADE methods. MAIN RESULTS: Eighteen RCTs with 1250
participants met our inclusion criteria. The studies were conducted in hospital
settings in low, middle and high income countries.Blood lossWe found significant
reductions in blood loss with the following interventions: vaginal misoprostol (2
RCTs, 89 women: MD -97.88 ml, 95% CI -125.52 to -70.24; I(2) = 43%; moderate
quality evidence); intramyometrial vasopressin (3 RCTs, 128 women: MD -245.87 ml,
95% CI -434.58 to -57.16; I(2) = 98%; moderate-quality evidence); intramyometrial
bupivacaine plus epinephrine (1 RCT, 60 women: MD -68.60 ml, 95% CI -93.69 to
43.51; low-quality evidence); intravenous tranexamic acid (1 RCT, 100 women: MD
243 ml, 95% CI -460.02 to -25.98; low-quality evidence); gelatin-thrombin matrix
(1 RCT, 50 women: MD -545.00 ml, 95% CI -593.26 to -496.74; low-quality
evidence); intravenous ascorbic acid (1 RCT, 102 women: MD -411.46 ml, 95% CI
502.58 to -320.34; low-quality evidence); vaginal dinoprostone (1 RCT, 108 women:
MD -131.60 ml, 95% CI -253.42 to -9.78; low-quality evidence); loop ligation of
the myoma pseudocapsule (1 RCT, 70 women: MD -305.01 ml, 95% CI -354.83 to
255.19; low-quality evidence); and a fibrin sealant patch (1 RCT, 70 women: MD
26.50 ml, 95% CI -44.47 to -8.53; low-quality evidence). We found evidence of
significant reductions in blood loss with a polyglactin suture (1 RCT, 28 women:
MD -1870.0 ml, 95% CI -2547.16 to 1192.84) or a Foley catheter (1 RCT, 93 women:
MD -240.70 ml, 95% CI -359.61 to -121.79) tied around the cervix. However,
pooling data from these peri-cervical tourniquet RCTs revealed significant
heterogeneity of the effects (2 RCTs, 121 women: MD (random) -1019.85 ml, 95% CI
2615.02 to 575.32; I(2) = 95%; low-quality evidence). There was no good evidence
of an effect on blood loss with oxytocin, morcellation or clipping of the uterine
artery.Need for blood transfusion We found significant reductions in the need for
blood transfusion with vasopressin (2 RCTs, 90 women: OR 0.15, 95% CI 0.03 to
0.74; I(2) = 0%; moderate-quality evidence); peri-cervical tourniquet (2 RCTs,
121 women: OR 0.09, 95% CI 0.01 to 0.84; I(2) = 69%; low-quality evidence);
gelatin-thrombin matrix (1 RCT, 100 women: OR 0.01, 95% CI 0.00 to 0.10; low
quality evidence) and dinoprostone (1 RCT, 108 women: OR 0.17, 95% CI 0.04 to
0.81; low-quality evidence), but no evidence of effect on the need for blood
transfusion with misoprostol, oxytocin, tranexamic acid, ascorbic acid, loop
ligation of the myoma pseudocapsule and a fibrin sealant patch.There were
insufficient data on the adverse effects and costs of the different
interventions. AUTHORS' CONCLUSIONS: At present there is moderate-quality
evidence that misoprostol may reduce bleeding during myomectomy, and low-quality
evidence that bupivacaine plus epinephrine, tranexamic acid, gelatin-thrombin
matrix, a peri-cervical tourniquet, ascorbic acid, dinoprostone, loop ligation
and a fibrin sealant patch may reduce bleeding during myomectomy. There is no
evidence that oxytocin, morcellation and temporary clipping of the uterine artery
reduce blood loss. Further well designed studies are required to establish the
effectiveness, safety and costs of different interventions for reducing blood
loss during myomectomy.
PMID- 25125319
TI - Which one is associated with nonalcoholic fatty liver disease? Small muscle mass
or large fat mass.
PMID- 25125318
TI - Complete remission of paraneoplastic vanishing bile duct syndrome after the
successful treatment of Hodgkin's lymphoma: a case report and review of the
literature.
AB - BACKGROUND: Vanishing bile duct syndrome has been associated with different
pathologic conditions (adverse drug reactions, autoimmune diseases, graft versus
host disease, and cancer). Though its causes are unknown, an immune-related
pathogenesis is the most likely one. Vanishing bile duct syndrome can evolve to
hepatic failure and, eventually, to death. The treatment is uncertain, but it
needs the resolution of the underlying pathologic condition. CASE PRESENTATION:
We describe the association of Hodgkin's lymphoma with a syndrome characterized
by cholestasis, aminotransferase elevation and an histological picture of bile
duct loss. All other causes of hepatic function impairment were excluded (in
particular, drugs, viral and autoimmune related diseases) eventually leading to
the diagnosis of vanishing bile duct syndrome. Despite the fact that the
dysfunction is not caused by hepatic Hodgkin's lymphoma involvement, liver
impairment can limit the optimal therapy of Hodgkin's lymphoma. A treatment
consisting of ursodeoxycholic acid, prednisone, and full dose chemotherapy
restored hepatic function and achieved complete and long-lasting remission of
Hodgkin's lymphoma. CONCLUSION: We reviewed all case reports showing that
vanishing bile duct syndrome is a dismal paraneoplastic syndrome being fatal in a
high proportion of patients if not adequately treated. Indeed, this syndrome
requires both an early recognition and an appropriate aggressive treatment
consisting of full dose upfront chemotherapy which is the only way to achieve a
resolution of the vanishing bile duct syndrome. Delayed or reduced intensity
treatments unfavorably correlate with survival.
PMID- 25125321
TI - Perception of e-cigarette harm and its correlation with use among U.S.
adolescents.
AB - INTRODUCTION: U.S. adolescents increasingly use e-cigarettes. The perceived harm
of e-cigarettes has not been described, nor has the correlation between harm
perception and e-cigarette use been assessed. This study examines correlates of e
cigarette harm perception and use of e-cigarettes in a national survey. METHODS:
We used cross-sectional nationally representative data from the 2012 National
Youth Tobacco Survey (n = 24,658). Cross-tabulations and multivariate ordered
probit and logistic regression models were employed to assess relative harm
perception and e-cigarette use. RESULTS: Half of U.S. adolescents had heard of e
cigarettes. Of these, 13.2% (95% confidence interval [CI] = 11.7-14.9) and 4.0%
(95% CI = 3.4-4.7) reported ever or currently using e-cigarettes, respectively.
Of those aware of e-cigarettes, 34.2% (95% CI = 32.8-35.6) believed e-cigarettes
were less harmful than cigarettes. Among those trying e-cigarettes, 71.8% (95% CI
= 69.0-74.5) believed e-cigarettes were comparatively less harmful. Females and
those >= 17 years old were more likely to perceive e-cigarettes as more harmful
relative to cigarettes, while on average Whites, users of other tobacco products,
and those with family members who used tobacco were more likely to perceive e
cigarettes as comparatively safer. Among cigarette-naive e-cigarette users, use
of other tobacco products and perceived harm reduction by e-cigarettes were,
respectively, on average associated with 1.6 and 4.1 percentage-point increases
in e-cigarette use. CONCLUSIONS: Perception of e-cigarettes as less harmful than
conventional cigarettes was associated with increased e-cigarette use, including
among cigarette-naive e-cigarette users. These findings should prompt further
scientific investigation and merit attention from regulators.
PMID- 25125323
TI - One-pot consecutive catalysis by integrating organometallic catalysis with
organocatalysis.
AB - The present study integrates two types of catalysis, namely, organometallic
catalysis and organocatalysis in one reaction pot. In this process, the product
of the first catalytic cycle acts as catalytic component for next catalytic
cycle. The abnormal N-heterocyclic carbene-copper-based organometallic catalyst
acts as an efficient catalyst for a click reaction to provide triazole, which, in
turn, acts as an efficient organocatalyst for different organic transformations,
for example, aza-Michael addition and multicomponent reactions, in a consecutive
fashion in the same reaction pot.
PMID- 25125320
TI - Off-treatment virologic relapse and outcomes of re-treatment in chronic hepatitis
B patients who achieved complete viral suppression with oral nucleos(t)ide
analogs.
AB - BACKGROUND: The durability of off-treatment virologic responses has not been
fully elucidated in chronic hepatitis B (CHB) patients who have previously
achieved complete virologic suppression with nucleos(t)ide analog (NA) therapy.
This study aimed to assess off-treatment virologic relapse rates and to
characterize the outcomes of subsequent re-treatment in CHB patients who have
discontinued oral NA following complete virologic suppression. METHODS: Ninety
five CHB patients who showed complete virologic suppression were withdrawn from
NAs: entecavir, lamivudine, and clevudine in 67, 15, and 13 patients,
respectively. Consolidation therapy was given for 6 and 12 months for HBeAg
positive and -negative CHB, respectively, before cessation. Virologic relapse was
managed with the same NA that had induced complete virologic response before
discontinuation. RESULTS: The cumulative rates of virologic relapse at 12 and 24
months were 73.8% and 87.1%, respectively. The relapse rates were independent of
HBeAg positivity, HBeAg seroconversion, and type of oral NA. In a multivariate
analysis, duration of oral NA therapy was the only significant predicting factor
associated with off-treatment virologic relapse. Although the majority of
patients regained complete virologic suppression, some patients did not respond
to re-treatment with the initial NA and developed genotypic resistance.
CONCLUSIONS: NA consolidation therapy for 6 and 12 months is associated with high
off-treatment virologic relapse in HBeAg-positive and -negative CHB patients,
respectively. Drugs with high genetic barriers to resistance should be considered
as a rescue therapy for off-treatment relapse in CHB.
PMID- 25125322
TI - Prevalence and determinants of secondhand smoke exposure among women in
Bangladesh, 2011.
AB - BACKGROUND AND OBJECTIVES: The population of Bangladesh is highly susceptible to
secondhand smoke (SHS) exposure due to high smoking rates and low awareness about
the harmful effects of SHS. This study aims to determine the prevalence of SHS
exposure and highlight the essential determinants in developing successful
strategies to prevent adverse health effects in Bangladesh. METHODS: The analysis
is based on the Bangladesh Demographic Health Survey 2011, in which 17,749 women
in the reproductive age group (12-49 years) were included. The information
regarding SHS exposure at home was derived from the question: "How often does
anyone smoke inside your house?" The variable was recoded into 3 groups: daily
exposure, low exposure (exposed weekly, monthly, or less than monthly), and no
SHS exposure. We performed descriptive and bivariable analyses and multinomial
logistic regression. RESULTS: A total of 46.7% of the women reported high
exposure to SHS at home. According to the multinomial logistic regression model,
relatively lower education and lower wealth index were significantly associated
with daily SHS exposure at home. The exposure differed significantly between the
divisions of Bangladesh. Having children at home (vs. not) and being Islamic
(compared to other religious affiliations) were protective factors. CONCLUSIONS:
The study indicates that women from socioeconomically disadvantaged households
are more likely to experience daily exposure to SHS at home. Therefore,
especially these groups have to be targeted to reduce tobacco consumption. In
addition to aspects of legislation, future strategies need to focus educational
aspects to improve the population's health status in Bangladesh.
PMID- 25125328
TI - How are we managing sudden sensorineural hearing loss in the United Kingdom?: our
experience.
PMID- 25125325
TI - MRS water resonance frequency in childhood brain tumours: a novel potential
biomarker of temperature and tumour environment.
AB - (1)H MRS thermometry has been investigated for brain trauma and hypothermia
monitoring applications but has not been explored in brain tumours. The proton
resonance frequency (PRF) of water is dependent on temperature but is also
influenced by microenvironment factors, such as fast proton exchange with
macromolecules, ionic concentration and magnetic susceptibility. (1)H MRS has
been utilized for brain tumour diagnostic and prognostic purposes in children;
however, the water PRF measure may provide complementary information to further
improve characterization. Water PRF values were investigated from a repository of
MRS data acquired from childhood brain tumours and children with apparently
normal brains. The cohort consisted of histologically proven glioma (22),
medulloblastoma (19) and control groups (28, MRS in both the basal ganglia and
parietal white matter regions). All data were acquired at 1.5 T using a short TE
(30 ms) single voxel spectroscopy (PRESS) protocol. Water PRF values were
calculated using methyl creatine and total choline. Spectral peak amplitude
weighted averaging was used to improve the accuracy of the measurements. Mean PRF
values were significantly larger for medulloblastoma compared with glioma, with a
difference in the means of 0.0147 ppm (p < 0.05), while the mean PRF for glioma
was significantly lower than for the healthy cohort, with a difference in the
means of 0.0061 ppm (p < 0.05). This would suggest the apparent temperature of
the glioma group was ~1.5 degrees C higher than the medulloblastomas and ~0.7
degrees C higher than a healthy brain. However, the PRF shift may not reflect a
change in temperature, given that alterations in protein content, microstructure
and ionic concentration contribute to PRF shifts. Measurement of these effects
could also be used as a supplementary biomarker, and further investigation is
required. This study has shown that the water PRF value has the potential to be
used for characterizing childhood brain tumours, which has not been reported
previously.
PMID- 25125326
TI - Probing the size limit for nanomedicine penetration into Burkholderia multivorans
and Pseudomonas aeruginosa biofilms.
AB - Encapsulation of antibiotics into nanoparticles is a potential strategy to
eradicate biofilms. To allow further optimization of nanomedicines for biofilm
eradication, the influence of the nanoparticle size on the penetration into dense
biofilm clusters needs to be investigated. In the present study, the penetration
of nanoparticles with diameters ranging from 40 to 550 nm into two biofilms,
Burkholderia multivorans LMG 18825 and Pseudomonas aeruginosa LMG 27622, was
evaluated using confocal microscopy. Through image analysis, the percentage of
particles able to penetrate into dense biofilm clusters was calculated. The size
cut off for optimal penetration into biofilm clusters was located around 100-130
nm for both biofilms. The mesh size of the biofilm matrix and the size of the
channels in between the bacteria of the clusters are two factors which likely
play a role in the exclusion of the larger particles. For B. multivorans, a sharp
drop in the penetration into the clusters is seen for particles larger than 130
nm while for P. aeruginosa, a more gradual decrease in penetration could be
observed. The overall penetration of the nanoparticles was slightly lower for P.
aeruginosa than for B. multivorans. Based on these results, it could be concluded
that nanocarriers of about 100 nm and smaller are good candidates to improve the
treatment of chronic pulmonary biofilms in CF patients. Furthermore, the confocal
microscopy method demonstrated here is a useful tool to assess the penetration of
nanomedicines in biofilm clusters. Such information is important to optimize
nanomedicine formulations for the treatment of biofilm infections.
PMID- 25125327
TI - Lysosomal capturing of cytoplasmic injected nanoparticles by autophagy: an
additional barrier to non viral gene delivery.
AB - Autophagy or 'self-eating' is a process by which defective organelles and foreign
material can be cleared from the cell's cytoplasm and delivered to the lysosomes
in which degradation occurs. It remains an open question, however, whether
nanoparticles that did not enter the cell through endocytosis can also be
captured from the cytoplasm by autophagy. We demonstrate that nanoparticles that
are introduced directly in the cytoplasm of the cells by microinjection, can
trigger an autophagy response. Moreover, both polystyrene beads and plasmid DNA
containing poly-ethylene-imine complexes colocalize with autophagosomes and
lysosomes, as was confirmed by electron microscopy. This indicates that
cytoplasmic capturing of nanoparticles can occur by an autophagy response. The
capturing of nanoparticles from the cytoplasm most likely limits the time frame
in which efficient nucleic acid delivery can be obtained. Hence, autophagy forms
an additional barrier to non-viral gene delivery, a notion that was not often
taken into account before. Furthermore, these findings urge us to reconsider the
idea that a single endosomal escape event is sufficient to have the long-lasting
presence of nanoparticles in the cytoplasm of the cells.
PMID- 25125329
TI - Effect of labor on plasma concentrations and postpartum clearance of cell-free,
pregnancy-associated, placenta-specific microRNAs.
AB - OBJECTIVE: This study aimed to investigate the effect of labor on plasma
concentrations of cell-free, pregnancy-associated, placenta-specific microRNAs
(miRNAs) before and after delivery. METHOD: In the non-labor group (32 women),
cesarean section (C/S) was performed before the beginning of labor. In the labor
group (32 women), C/S was performed after the beginning of labor. Plasma
concentrations of cell-free, pregnancy-associated, placenta-specific miRNAs (miR
515-3p, miR-517a, miR-517c, and miR-518b) were measured by real-time quantitative
PCR. Each miRNA concentration was compared between the non-labor and labor
groups. RESULTS: Before C/S, plasma concentrations of cell-free, pregnancy
associated, placenta-specific miRNAs in the labor group were significantly higher
than those in the non-labor group (P = 0.001 for 515-3p, P = 0.002 for 517a, P =
0.001 for 517c, and P = 0.003 for 518b). Twenty-four hours after delivery, plasma
concentrations of cell-free, pregnancy-associated, placenta-specific miRNAs in
the labor group were significantly higher than those in the non-labor group (P =
0.002 for 515-3p, P = 0.017 for 517a, P = 0.043 for 517c, and P = 0.009 for
518b). CONCLUSION: The presence of labor affects cell-free, pregnancy-associated,
placenta-specific miRNA levels in maternal plasma. Labor also affects postpartum
clearance of these miRNAs 24 h after delivery.
PMID- 25125330
TI - Neural drive to respiratory muscles in the spontaneously breathing rat pup.
AB - The neonatal rodent serves as useful and appropriate model within which to study
respiratory system development. Despite an extensive literature that documents
respiratory control in vitro, in vivo studies have relied upon whole body
plethysmography to determine measures of respiratory frequency and tidal volume.
However, plethysmography restricts access to the animal and thus, respiratory
muscle electromyographic (EMG) activities have not been recorded in these studies
previously. Electromyography yields accurate information about neural respiratory
center output to the musculature and therefore, about the control of breathing in
the intact animal. In this case, we documented neural drive to respiratory pump
and upper airway muscles, electrocardiogram (ECG) and chest wall motions in rat
pups up to 10 days of age noting sighs, spontaneous central apneas and hypopneas
in room air and with successive increments in fractional inspired CO2 (FICO2).
Our findings underscore the advantages of EMG recordings for purposes of
determining the magnitude and distribution of neural drive to respiratory muscles
and for characterizing the full range of breathing behaviors exhibited by rats in
the early postnatal period.
PMID- 25125331
TI - In reference to Snoring and carotid artery intima-media thickness.
PMID- 25125333
TI - Practical aspects of monochromators developed for transmission electron
microscopy.
AB - A few practical aspects of monochromators recently developed for transmission
electron microscopy are briefly reviewed. The basic structures and properties of
four monochromators, a single Wien filter monochromator, a double Wien filter
monochromator, an omega-shaped electrostatic monochromator and an alpha-shaped
magnetic monochromator, are outlined. The advantages and side effects of these
monochromators in spectroscopy and imaging are pointed out. A few properties of
the monochromators in imaging, such as spatial or angular chromaticity, are also
discussed.
PMID- 25125332
TI - Trehalose alleviates PC12 neuronal death mediated by lipopolysaccharide
stimulated BV-2 cells via inhibiting nuclear transcription factor NF-kappaB and
AP-1 activation.
AB - Inflammation is implicated in the pathogenesis of Parkinson's disease (PD).
Trehalose is a disaccharide which exhibits a variety of effects like anti
aggregation, autophagy enhancement in PD. It has also been known to suppress
inflammation in many experimental models, involving endotoxin shock, murine dry
eye and subarachnoid hemorrhage. However, whether trehalose has an anti
inflammation effect on PD is largely unknown. In the present study, we found
trehalose inhibited generation of interleukin-1beta, interleukin-6, tumor
necrosis factor-alpha, and nitric oxide in the conditioned medium released from
lipopolysaccharide (LPS)-stimulated BV-2 cells. LPS-induced nuclear transcription
factors of NF-kappaB and AP-1 activation were also inhibited by trehalose. Then
the conditioned medium of BV-2 cells was applied to PC12 neurons. As a result,
both MTT and LDH indicated that trehalose decreased PC12 neuronal death. TUNEL
assay showed that trehalose suppressed apoptosis of PC12 neurons. These results
implied that trehalose exerted a protective effect on PC12 neurons against the
neurotoxic effect triggered by BV-2 microglial activation through inhibiting NF
kappaB and AP-1 activation and inflammatory mediators and cytokines production in
BV-2 cells.
PMID- 25125335
TI - Proteasome inhibitors with photocontrolled activity.
AB - Proteasome inhibitors are widely used in cancer treatment as chemotherapeutic
agents. However, their employment often results in severe side effects, due to
their non-specific cytotoxicity towards healthy tissue. This problem might be
overcome by using a photopharmacological approach, that is, by attaining
external, dynamic, spatiotemporal photocontrol over the activity of a cytotoxic
agent, achieved by the introduction of a photoswitchable moiety into its
molecular structure. Here we describe the design, synthesis, and activity of
photoswitchable proteasome inhibitors. Substantial differences in proteasome
inhibitory activity in cell extracts were observed before and after irradiation
with light. The presented results show potential for the development of
chemotherapeutic agents that can be switched on and off with light, constituting
a new strategy for spatiotemporally modulating proteasomal activity.
PMID- 25125334
TI - Functional characterization and categorization of missense mutations that cause
methylmalonyl-CoA mutase (MUT) deficiency.
AB - Methylmalonyl-CoA mutase (MUT) is an essential enzyme in propionate catabolism
that requires adenosylcobalamin as a cofactor. Almost 250 inherited mutations in
the MUT gene are known to cause the devastating disorder methylmalonic aciduria;
however, the mechanism of dysfunction of these mutations, more than half of which
are missense changes, has not been thoroughly investigated. Here, we examined 23
patient missense mutations covering a spectrum of exonic/structural regions,
clinical phenotypes, and ethnic populations in order to determine their influence
on protein stability, using two recombinant expression systems and a
thermostability assay, and enzymatic function by measuring MUT activity and
affinity for its cofactor and substrate. Our data stratify MUT missense mutations
into categories of biochemical defects, including (1) reduced protein level due
to misfolding, (2) increased thermolability, (3) impaired enzyme activity, and
(4) reduced cofactor response in substrate turnover. We further demonstrate the
stabilization of wild-type and thermolabile mutants by chemical chaperones in
vitro and in bacterial cells. This in-depth mutation study illustrates the tools
available for MUT enzyme characterization, guides future categorization of
further missense mutations, and supports the development of alternative,
chaperone-based therapy for patients not responding to current treatment.
PMID- 25125336
TI - Osteoclast inhibition impairs chondrosarcoma growth and bone destruction.
AB - Because Chondrosarcoma is resistant to available chemotherapy and radiation
regimens, wide resection is the mainstay in treatment, which frequently results
in high morbidity and which may not prevent local recurrence. There is a clear
need for improved adjuvant treatment of this malignancy. We have observed the
presence of osteoclasts in the microenvironment of chondrosarcoma in human
pathological specimens. We utilized the Swarm rat chondrosarcoma (SRC) model to
test the hypothesis that osteoclasts affect chondrosarcoma pathogenesis. We
implanted SRC tumors in tibia of Sprague-Dawley rats and analyzed bone
histologically and radiographically for bone destruction and tumor growth. At
three weeks, tumors invaded local bone causing cortical disruption and trabecular
resorption. Bone destruction was accompanied by increased osteoclast number and
resorbed bone surface. Treatment of rats with the zoledronic acid prevented
cortical destruction, inhibited trabecular resorption, and resulted in decreased
tumor volume in bone. To confirm that inhibition of osteoclasts per se, and not
off-target effects of drug, was responsible for the prevention of tumor growth
and bone destruction, we implanted SRC into osteopetrotic rat tibia. SRC-induced
bone destruction and tumor growth were impaired in osteopetrotic bone compared
with control bone. The results from our animal model demonstrate that osteoclasts
contribute to chondrosarcoma-mediated bone destruction and tumor growth and may
represent a therapeutic target in particular chondrosarcoma patients.
PMID- 25125337
TI - Novel MTCYB mutation in a young patient with recurrent stroke-like episodes and
status epilepticus.
AB - The acronym "MELAS" (mitochondrial encephalomyopathy with lactic acidosis and
stroke-like episodes) denotes patients with histological, biochemical and/or
molecular evidence of mitochondrial disease who experience stroke-like episodes.
Here we report on a girl with repeated stroke-like episodes and status
epilepticus, who was diagnosed with MELAS due to a novel mitochondrial cytochrome
b gene (MTCYB) mutation (m.15092G>A, which predicts p.G116S). Western blotting
and in silico analyses suggested that this mutation could affect the stability of
complex III. Cytochrome b is the only mtDNA-encoded subunit of respiratory chain
complex III. Mutations in MTCYB have been associated with isolated mitochondrial
myopathy and exercise intolerance, and rarely with multisystem and/or central
nervous system involvement. If the m.3243A>G and other common MELAS mutations are
absent in several tissues, MTCYB should be sequenced from muscle in patients with
stroke-like episodes, especially if muscle histology does not support a
mitochondrial myopathy and lactic acidosis is absent.
PMID- 25125338
TI - Type 1 diabetes mellitus. Comparison between the association with PTPN22 genotype
and the association with ACP1-ADA1 joint genotype.
AB - AIMS: T1D has been found associated with PTPN22 and with ACP1-ADA1 joint
genotype. In the present note we have collected further data to evaluate the
relative importance of the two systems and to search for possible interaction of
PTPN22 with ACP1-ADA1 joint genotype. METHODS: We have studied 314 children with
T1D and 770 controls from the White population of Central Italy. ACP1, ADA1 and
PTPN22 genotypes were determined by DNA analysis. Chi square test of independence
was performed by SPSS program and three way contingency analysis by a log-linear
model. RESULTS: Both carriers of *T allele of PTPN22 and subjects with ACP1 *A/*A
and *A/*B genotypes carrying ADA1 *2 allele show an increase of susceptibility to
T1D. There is evidence of additive effect (p=0.0002) but not of epistatic
interaction. The association of T1D with ACP1-ADA1 joint genotype is stronger
(OR=2.494, 95% C.I. 1.509-4.122) as compared to that with PTPN22 (OR=1.825, 95%
C.I. 1.951-2.859). CONCLUSIONS: It has been suggested that the *T variant of
PTPN22 inhibits T cell receptor signaling leading to failure to delete
autoreactive T cells during intrathymic selection resulting in increased
susceptibility to autoimmune disorders. The joint genotype ACP1 *A/*A and *A/*B
carrying the ADA1 *2 allele shows a decreased activity of ACP1 resulting in a
lowering of Zap70 activity that may decrease T cell receptor signaling with an
additive effects to the inhibition due to the *T variant of PTPN22.
PMID- 25125340
TI - Isolated hepatic perfusion with oxaliplatin combined with 100 mg melphalan in
patients with metastases confined to the liver: A phase I study.
AB - AIM: To improve isolated hepatic perfusion (IHP), we performed a phase I dose
escalation study to determine the optimal oxaliplatin dose in combination with a
fixed melphalan dose. METHODS: Between June 2007 and July 2008, 11 patients,
comprising of 8 colorectal cancer and 3 uveal melanoma patients and all with
isolated liver metastases, were treated with a one hour IHP with escalating doses
of oxaliplatin combined with 100 mg melphalan. Samples of blood and perfusate
were taken during IHP treatment for pharmacokinetic analysis of both drugs and
patients were monitored for toxicity, response and survival. RESULTS: Dose
limiting sinusoidal obstruction syndrome (SOS) occurred at 150 mg oxaliplatin.
The areas under the concentration-time curves (AUC) of oxaliplatin at the maximal
tolerated dose (MTD) of 100 mg oxaliplatin ranged from 11.9 mg/L h to 16.5 mg/L
h. All 4 patients treated at the MTD showed progressive disease 3 months after
IHP. CONCLUSIONS: In view of similar and even higher doses of oxaliplatin applied
in both systemic treatment and hepatic artery infusion (HAI), applying this dose
in IHP is not expected to improve treatment results in patients with isolated
hepatic metastases.
PMID- 25125339
TI - The DEXLIFE study methods: identifying novel candidate biomarkers that predict
progression to type 2 diabetes in high risk individuals.
AB - The incidence of type 2 diabetes (T2D) is rapidly increasing worldwide and T2D is
likely to affect 592 million people in 2035 if the current rate of progression is
continued. Today, patients are diagnosed with T2D based on elevated blood
glucose, either directly or indirectly (HbA1c). However, the information on
disease progression is limited. Therefore, there is a need to identify novel
early markers of glucose intolerance that reflect the underlying biology and the
overall physiological, metabolic and clinical characteristics of progression
towards diabetes. In the DEXLIFE study, several clinical cohorts provide the
basis for a series of clinical, physiological and mechanistic investigations in
combination with a range of--omic technologies to construct a detailed metabolic
profile of high-risk individuals across multiple cohorts. In addition, an
exercise and dietary intervention study is conducted, that will assess the impact
on both plasma biomarkers and specific functional tissue-based markers. The
DEXLIFE study will provide novel diagnostic and predictive biomarkers which may
not only effectively detect the progression towards diabetes in high risk
individuals but also predict responsiveness to lifestyle interventions known to
be effective in the prevention of diabetes.
PMID- 25125341
TI - A comparison of fibrin sealant versus standard closure in the reduction of
postoperative morbidity after groin dissection: A systematic review and meta
analysis.
AB - BACKGROUND: Groin dissection is commonly performed in patients with lower limb
malignant conditions such as malignant melanoma, vulvar, penile, anal and scrotal
carcinomas with an associated high complication rate. Numerous surgical
strategies have been suggested to reduce morbidity. We aimed to systematically
review one of those methods - fibrin sealant (FS) - in comparison to standard
closure (SC) in reducing postoperative morbidity from groin dissection. METHODS:
A systematic search of the literature, study selection and data extraction using
an independent screening process, assessment of risk of bias and statistical data
analysis was performed. Only randomised controlled trials (RCTs) comparing fibrin
sealant to standard care in patients with malignant disease undergoing groin
dissection reporting at least one outcome measure relating to postoperative
complications were included in the review. RESULTS: A total of 6 RCTs were
included. There were no statistically significant differences in postoperative
surgical site infection (SSI) rates between FS and SC. The overall incidence of
wound infection in the FS group was 32% (43/133) compared to 34% (45/132) in the
SC group. (Pooled risk ratio = 0.0.94 [0.68, 1.32]; 95% CI; P = 0.74). The
incidence of seroma for the FS group (30/133) and the SC group (30/132) did not
differ (Pooled risk ratio = 1.03 [0.67, 1.58]; 95% CI; P value = 0.90).
Complication rates were similar between groups. CONCLUSION: Based on current
evidence, fibrin sealant does not significantly reduce morbidity in patients
undergoing groin dissection for the management of malignant disease when compared
to standard closure techniques.
PMID- 25125343
TI - Next-generation sequence testing expands research into causes of hearing loss:
scientists examine role of multiple mutations in individual cases.
PMID- 25125344
TI - Newborn bloodspot retention reinstated in Minnesota: practice expected to benefit
larger newborn screening studies, public health, disease research.
PMID- 25125342
TI - Anatomy and ontogeny of a novel hemodynamic organ in zebrafish.
AB - The zebrafish maxillary barbel can protract and retract in response to stimuli,
and appears connected to a prominent blood sinus on the lateral aspect of the
maxillary bone. However, the mechanism of barbel movement is not described. Using
whole-mount phalloidin staining of the sinus region, we observed long filamentous
actin cables, suggesting highly organized vascular smooth muscle cells,
surrounding an endothelial chamber. Although the chamber is variably filled by
erythrocytes in vivo, cardiac injection of fluorescent dextrans shows that it
consistently contains plasma. Full-thickness confocal imaging of dextran-injected
adults containing EGFP(+) endothelial cells revealed a vascular complex with
three compartments, here named the distal bulb, central chamber, and accessory
chamber. The early ontogeny of all three compartments was confirmed in a whole
mount series of Tg(fli1a:EGFP) juveniles. In wild type adults, the fine structure
of each chamber was studied using paraffin- and plastic-section histochemistry
and transmission electron microscopy. The distal bulb and central chamber have
smooth muscle coats with luminally-elongated septa, forming semi-detached blood
filled lacunae. The central chamber walls and septa are extensively innervated by
small, unmyelinated axons, as confirmed by immunohistochemical detection of
acetylated tubulin, a component of axonal cytoplasm. The accessory chamber
appears neither innervated nor muscularized, but is an endothelial cul-de-sac
with a thickened elastic adventitia, suggesting an extensible fluid reservoir. We
propose that we have identified a new organ in zebrafish, the maxillary barbel
blood sinus, whose neurovascular specializations may contribute to zebrafish
sensory biology and appendage control.
PMID- 25125346
TI - May the thyroid gland and thyroperoxidase participate in nitrosylation of serum
proteins and sporadic Parkinson's disease?
AB - The research group has detected nitrosative stress and a singular version of
nitrosylated serum alpha-synuclein in serum of Parkinson's disease (PD) patients.
Dysfunction of the thyroid gland has been proposed to be linked to this disease.
The aim of the study was to know if the thyroid gland is involved in idiopathic
PD and nitrosative stress. We studied 50 patients (early and advanced disease
patients), 35 controls, and 6 subjects with thyroidectomy. Clinical
characteristics, serum thyroperoxidase levels, and 3-nitrotyrosine proteins were
analyzed. Enzyme-linked immunosorbent assay and immunoblotting methods were
employed. The findings indicated that the prevalence of two thyroid dysfunctions
(hyper- or hypothyroidism) was not found to be different in patients relative to
controls. However, the levels of the enzyme thyroperoxidase were found to be
elevated in early disease patients (p<0.006), not in advanced disease subjects,
and these levels were negatively correlated with serum 3-nitrotyrosine proteins
(p<0.05), the indicators of nitrosative stress. The thyroidectomized subjects
showed very low levels of serum 3-nitrotyrosine proteins (78% reduction vs.
controls) and, among these proteins, the nitrosylated serum alpha-synuclein was
nearly absent. These observations lead to the hypothesis that the thyroid gland
and thyroperoxidase participate in nitrosylation of serum proteins and they could
influence Parkinsonian nitrosative stress as well as nitrosylation of serum alpha
synuclein, a potentially pathogenic factor.
PMID- 25125347
TI - Combining serum carbohydrate-deficient transferrin and hair ethyl glucuronide to
provide optimal information on alcohol use.
PMID- 25125348
TI - Detoxifying polyhalogenated catechols through a copper-chelating agent by forming
stable and redox-inactive hydrogen-bonded complexes with an unusual perpendicular
structure.
AB - The use of selective metal chelating agents with preference for binding of a
specific metal ion to investigate its biological role is becoming increasingly
common. We found recently that a well-known copper-specific chelator 2,9-dimethyl
1,10-phenanthroline (2,9-Me2OP) could completely inhibit the synergistic toxicity
induced by tetrachlorocatechol (TCC) and sodium azide (NaN3). However, its
underlying molecular mechanism is still not clear. Here, we show that the
protection by 2,9-Me2OP is not due to its classic copper-chelating property, but
rather due to formation of a multiple hydrogen-bonded complex between 2,9-Me2OP
and TCC, featuring an unusual perpendicular arrangement of the two binding
partners. The two methyl groups at the 2,9 positions in 2,9-Me2OP were found to
be critical to stabilize the 2,9-Me2OP/TCC complex due to steric hindrance, and
therefore completely prevents the generation of the reactive and toxic
semiquinone radicals by TCC/NaN3. This represents the first report showing that
an unexpected new protective mode of action for the copper "specific" chelating
agent 2,9-Me2OP by using its steric hindrance effect of the two CH3 groups not
only to chelate copper, but also to "chelate" a catechol through multiple H
bonding. These findings may have broad biological implications for future
research of this widely used copper-chelating agent and the ubiquitous catecholic
compounds.
PMID- 25125350
TI - Controlled release of therapeutic antibody formats.
AB - The local administration of antibodies can represent in many cases a significant
improvement for antibody-based therapies. The benefits of local delivery include
high drug concentrations at the target site, the possibility of lower drug dosing
and less systemic drug exposure. Currently, the most relevant delivery sites for
therapeutic antibodies are the posterior segments of the eye, mucosal surfaces,
the articular joints and the central nervous system (CNS). In addition, the oral
and pulmonary route may enable non-invasive systemic antibody delivery. However,
local antibody delivery to these sites is characterized by short drug residence
times and a low compliance of administration. Controlled release (CR) systems can
address these limitations and, thereby, enable and improve local delivery
applications by achieving long lasting local drug concentrations, improved
efficacy-dosing ratios and reduced treatment-associated side effects. The
requirements for CR antibody formulations are more complex compared to
conventional CR systems for small molecules, and their development poses an
enormous technical challenge. Therefore, the review highlights experiences and
challenges gathered in the development of the different CR systems for antibodies
to date. Additionally, the unmet technological needs encountered in the field are
described. This includes a critical evaluation of the limited capability of
various CR systems to preserve antibody stability, delivery site specific
considerations, as well as the processability of a CR system with a particular
focus on drug loading and injectability. We believe that the success of CR and
local delivery approaches could create an enormous added value for patients in
the future.
PMID- 25125349
TI - Effects of a eucaloric reduced-carbohydrate diet on body composition and fat
distribution in women with PCOS.
AB - OBJECTIVE: To determine if consumption of a reduced-carbohydrate (CHO) diet would
result in preferential loss of adipose tissue under eucaloric conditions, and
whether changes in adiposity were associated with changes in postprandial insulin
concentration. METHODS: In a crossover-diet intervention, 30 women with PCOS
consumed a reduced-CHO diet (41:19:40% energy from CHO:protein:fat) for 8 weeks
and a standard diet (55:18:27) for 8 weeks. Body composition by DXA and fat
distribution by CT were assessed at baseline and following each diet phase.
Insulin AUC was obtained from a solid meal test (SMT) during each diet phase.
RESULTS: Participants lost 3.7% and 2.2% total fat following the reduced-CHO diet
and STD diet, resp. (p<0.05 for difference between diets). The reduced-CHO diet
induced a decrease in subcutaneous-abdominal, intra-abdominal, and thigh
intermuscular adipose tissue (-7.1%, -4.6%, and -11.5%, resp.), and the STD diet
induced a decrease in total lean mass. Loss of fat mass following the reduced CHO
diet arm was associated with lower insulin AUC (p<0.05) during the SMT.
CONCLUSIONS: In women with PCOS, consumption of a diet lower in CHO resulted in
preferential loss of fat mass from metabolically harmful adipose depots, whereas
a diet high in CHO appeared to promote repartitioning of lean mass to fat mass.
PMID- 25125351
TI - The key role of caregiver confidence in the caregiver's contribution to self-care
in adults with heart failure.
AB - BACKGROUND: Caregivers play an important role in contributing to heart failure
(HF) patients' self-care but no prior studies have examined the caregivers'
contributions to HF patients' self-care and no prior studies have examined
potential determinants of the caregivers' contribution to HF patients' self-care.
AIMS: The purpose of this study was to describe the caregivers' contribution to
HF patients' self-care and identify its determinants. METHODS: The study design
involved a secondary analysis of cross-sectional data. Caregivers' contributions
were measured with the Caregiver's Contribution to Self-care of HF Index (CC
SCHFI) which measures the caregiver's contribution to self-care maintenance and
management and caregiver confidence in contributing to HF patient's self-care.
Potential determinants were measured using a socio-demographic questionnaire
completed by caregivers and patients, and patient clinical data was obtained from
the medical record. RESULTS: Data from 515 caregiver/patient dyads were analyzed.
Most (55.5%) patients were male (mean age 75.6 years) and most (52.4%) caregivers
were female (mean age, 56.6 years). The caregivers' contribution to patients'
self-care maintenance was low in weight monitoring and physical activity but
higher in checking ankles, advising on low-salt foods and taking medicines. The
caregivers' contribution to patients' self-care management was low in symptom
recognition. When symptoms were recognized, caregivers advised patients to reduce
fluids and salt and call the provider but rarely advised to take an extra
diuretic. Caregiver confidence in the ability to contribute to patient self-care
explained a significant amount of variance in the caregiver's contribution.
CONCLUSION: These findings suggest that caregivers in this sample did not
contribute meaningfully to HF self-care. Providers should educate both HF
patients and caregivers. Interventions that improve caregiver confidence have the
potential to successfully increase the caregivers' contribution to patients' self
care.
PMID- 25125352
TI - The caregiver role in thromboprophylaxis management in atrial fibrillation: a
literature review.
AB - BACKGROUND: Atrial fibrillation is a common arrhythmia and a risk factor for
adverse events including stroke. People living with atrial fibrillation are
commonly elderly and have multiple comorbidities. The role of a caregiver in
supporting the individual to manage a chronic and complex condition has received
limited attention. OBJECTIVES: This review aims to summarize available
information on the caregiver role in atrial fibrillation, specifically in
promoting adherence to thromboprophylaxis and evidence for strategies to support
and enable the caregiver. DATA SOURCES: A review of electronic databases and
search engines was undertaken including Medline, Scopus and CINAHL. The search
terms 'atrial fibrillation', 'anticoagulation', 'carer', 'caregiver', 'family
support' were used. Dates searched were from January 1990 to November 2012.
RESULTS: The review found limited original clinical research studies. The
majority of the literature identified in the initial search included review
papers and work which recommends the inclusion of the caregiver in the care of
patients with atrial fibrillation but limited empirical evidence. CONCLUSIONS:
Caregivers have an essential role to play in advocacy, family centred care and
shared decision-making. This may influence thromboprophylaxis treatment choices
and potentially adherence. Assessment of caregiver needs and support should be
central to patient assessment and care planning. There is a need for clinical
intervention studies which more target and address the caregiver role.
PMID- 25125354
TI - Liquid scintillation spectrometry: a technique with future.
PMID- 25125353
TI - Post-discharge electrocardiogram Holter monitoring in recently hospitalised
individuals with chronic atrial fibrillation to enhance therapeutic monitoring
and identify potentially predictive phenotypes.
AB - BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia
managed in clinical practice. Maintenance of intended rate or rhythm control
following hospitalisation is a key therapeutic goal. AIMS: The purpose of this
study was to assess post-discharge maintenance of intended AF control and
classify potentially predictive heart rate (HR) phenotypes via electrocardiogram
(ECG) Holter monitoring. METHODS: In a sub-study of a multicentre randomised
controlled trial comparing AF-specific management with usual care, 24-hour ECG
Holter monitoring was undertaken in 133 patients 7-14 days post-discharge.
Intended rate and rhythm control were compared to Holter data. Analysis of the
frequency distribution of mean hour-to-hour differences identified those with
labile HRs. RESULTS: Mean age was 71 +/- 10 years, 67 (50%) were male and mean HR
was 72 +/- 14 bpm. Most (89%) had persistent AF (median time in AF=39% (IQR 0
100%)). Uncontrolled HR (>90 bpm for >10% of recording) occurred in 35 (26%)
patients and 49 (37%) patients did not achieve their intended rate (n=26) or
rhythm control (n=23). Patients in the upper quartile of mean hour-to-hour HR
variability were identified as persistently labile (n=33). A further group (n=22)
with periodically labile HRs was identified. Those with coronary artery disease
(OR 0.34; 95% CI 0.13-0.91, p=0.033) or renal disease/dysfunction (OR 0.24; 95%
CI 0.06-0.98, p=0.047) were less likely to demonstrate HR stability (n=78).
CONCLUSION: Post-discharge ECG Holter monitoring of AF patients represents a
valuable tool to identify deviations in intended rhythm/rate control and adjust
therapeutic management accordingly. It may also identify individuals who
demonstrate labile HRs.
PMID- 25125355
TI - Response to invited commentary: Methods to address control for confounding and
nonperfect randomization when using outcome distribution curves to estimate the
population-level impact of a public health intervention.
PMID- 25125359
TI - Hong Kong: an R&D hub in Asia for materials science and engineering.
PMID- 25125364
TI - Interdependencies among clinical research funders.
PMID- 25125365
TI - More ethical and more efficient clinical research: multiplex trial design.
AB - BACKGROUND: Today's clinical research faces challenges such as a lack of clinical
equipoise between treatment arms, reluctance in randomizing for multiple
treatments simultaneously, inability to address interactions and increasingly
restricted resources. Furthermore, many trials are biased by extensive exclusion
criteria, relatively small sample size and less appropriate outcome measures.
FINDINGS: We propose a 'Multiplex' trial design that preserves clinical equipoise
with a continuous and factorial trial design that will also result in more
efficient use of resources. This multiplex design accommodates subtrials with
appropriate choice of treatment arms within each subtrial. Clinical equipoise
should increase consent rates while the factorial design is the best way to
identify interactions. CONCLUSION: The multiplex design may evolve naturally from
today's research limitations and challenges, while principal objections seem
absent. However this new design poses important infrastructural, organisational
and psychological challenges that need in depth consideration.
PMID- 25125366
TI - Transcriptional activation of Fsp27 by the liver-enriched transcription factor
CREBH promotes lipid droplet growth and hepatic steatosis.
AB - Fat-specific protein 27 (Fsp27) is a lipid droplet-associated protein that
promotes lipid droplet (LD) growth and triglyceride (TG) storage in white
adipocytes. Fsp27 is also highly expressed in the steatotic liver and contributes
to TG accumulation. In this study we discovered that the liver produces
Fsp27beta, an alternative Fsp27 isoform, which contains 10 additional amino acids
at the N-terminus of the original Fsp27 (Fsp27alpha). White adipose tissue (WAT)
and the liver specifically expressed Fsp27alpha and Fsp27beta transcripts,
respectively, which were driven by distinct promoters. The Fsp27beta promoter was
activated by the liver-enriched transcription factor cyclic-AMP-responsive
element-binding protein H (CREBH) but not by peroxisome proliferator-activated
receptor gamma (PPARgamma), which activated the Fsp27alpha promoter. Enforced
expression of the constitutively active CREBH strongly induced Fsp27beta and the
human ortholog CIDEC2 in mouse hepatocytes and HepG2 cells, respectively. In
contrast, loss of CREBH decreased hepatic Fsp27beta in fasted mice, suggesting
that CREBH plays a critical role in Fsp27beta expression in the liver. Similar to
Fsp27alpha, Fsp27beta localized on the surface of lipid droplets and suppressed
lipolysis. Consequently, enforced expression of Fsp27beta or CREBH promoted lipid
droplet enlargement and TG accumulation in the liver. CONCLUSION: The CREBH
Fsp27beta axis is important for regulating lipid droplet dynamics and TG storage
in the liver.
PMID- 25125367
TI - Intratumor distribution and test-retest comparisons of physiological parameters
quantified by dynamic contrast-enhanced MRI in rat U251 glioma.
AB - The distribution of dynamic contrast-enhanced MRI (DCE-MRI) parametric estimates
in a rat U251 glioma model was analyzed. Using Magnevist as contrast agent (CA),
17 nude rats implanted with U251 cerebral glioma were studied by DCE-MRI twice in
a 24 h interval. A data-driven analysis selected one of three models to estimate
either (1) plasma volume (vp), (2) vp and forward volume transfer constant
(K(trans)) or (3) vp, K(trans) and interstitial volume fraction (ve),
constituting Models 1, 2 and 3, respectively. CA distribution volume (VD) was
estimated in Model 3 regions by Logan plots. Regions of interest (ROIs) were
selected by model. In the Model 3 ROI, descriptors of parameter distributions-
mean, median, variance and skewness--were calculated and compared between the two
time points for repeatability. All distributions of parametric estimates in Model
3 ROIs were positively skewed. Test-retest differences between population
summaries for any parameter were not significant (p >= 0.10; Wilcoxon signed-rank
and paired t tests). These and similar measures of parametric distribution and
test-retest variance from other tumor models can be used to inform the choice of
biomarkers that best summarize tumor status and treatment effects.
PMID- 25125370
TI - Alternative splicing regulation of APP exon 7 by RBFox proteins.
AB - RBFox proteins are well-known alternative splicing regulators. We have shown
previously that during neuronal differentiation of P19 cells induced by all-trans
retinoic acid and cell aggregation, RBFox1 shows markedly increased temporal
expression. To find its key splicing regulation, we examined the effect of RBFox1
on 33 previously reported and validated neuronal splicing events of P19 cells. We
observed that alternative splicing of three genes, specifically, amyloid
precursor protein (APP), disks large homolog 3 (DLG3), and G protein, alpha
activating activity polypeptide O (GNAO1), was altered by transient RBFox1
expression in HEK293 and HeLa cells. Moreover, an RBFox1 mutant (RBFox1FA) that
was unable to bind the target RNA sequence ((U)GCAUG) did not induce these
splicing events. APP generates amyloid beta peptides that are involved in the
pathology of Alzheimer's disease, and therefore we examined APP alternative
splicing regulation by RBFox1 and other splicing regulators. Our results
indicated that RBFox proteins promote the skipping of APP exon 7, but not the
inclusion of exon 8. We made APP6789 minigenes and observed that two (U)GCAUG
sequences, located upstream of exon 7 and in exon 7, functioned to induce
skipping of exon 7 by RBFox proteins. Overall, RBFox proteins may shift APP from
exon 7 containing isoforms, APP770 and APP751, toward the exon 7 lacking isoform,
APP695, which is predominant in neural tissues.
PMID- 25125369
TI - Astrocytic control of neural circuit formation: highlights on TGF-beta signaling.
AB - Brain function depends critically on the coordinated activity of presynaptic and
postsynaptic signals derived from both neurons and non-neuronal elements such as
glial cells. A key role for astrocytes in neuronal differentiation and circuitry
formation has emerged within the last decade. Although the function of glial
cells in synapse formation, elimination and efficacy has greatly increased, we
are still very far from deeply understanding the molecular and cellular mechanism
underlying these events. The present review discusses the mechanisms driving
astrocytic control of excitatory and inhibitory synapse formation in the central
nervous system, especially the mechanisms mediated by soluble molecules,
particularly those from the TGF-beta family. Further, we discuss whether and how
human astrocytes might contribute to the acquisition of human cognition. We argue
that understanding how astrocytic signals regulate synaptic development might
offer new insights into human perception, learning, memory, and cognition and,
ultimately, provide new targets for the treatment of neurological diseases.
PMID- 25125371
TI - Reference ranges for the volumes of fetal cardiac ventricular walls by three
dimensional ultrasound using spatiotemporal image correlation and virtual organ
computer-aided analysis and its validation in fetuses with congenital heart
diseases.
AB - OBJECTIVE: To establish reference values for the volumes of fetal cardiac
ventricular walls using three-dimensional ultrasonography (3DUS) and perform data
validation using fetuses with confirmed congenital heart disease (CHD). METHODS:
This prospective, cross-sectional study analyzed 371 singleton pregnancies
between 20w0d and 33w6d of gestation. Ventricular volumes were assessed using
spatiotemporal image correlation (STIC) and virtual organ computer-aided analysis
(VOCAL). We calculated the polynomial regressions, adjusted by the coefficient of
determination (R(2) ). To assess intra-observer concordance, the intraclass
correlation coefficient (ICC) was used. To validate the curves, the ventricular
wall volumes of 22 fetuses with CHD were evaluated. RESULTS: There was a good
correlation between these mean volumes and gestational age, and this correlation
was best represented by linear equations. Intra-observer concordance in assessing
the volumes of the right (ICC = 0.90) and left ventricular walls (ICC = 0.97) was
good. We observed that the volumes of the right and left ventricular walls were
altered (<5(th) percentile and/or >95(th) percentile) in 8/22 fetuses presenting
with CHD. CONCLUSION: The reference ranges for the volumes of the right and left
ventricular walls by 3DUS using STIC and VOCAL between 20w0d and 33w6d of
gestation were determinate, and they exhibited good intra-observer concordance.
PMID- 25125372
TI - Elongation of amyloid fibrils through lateral binding of monomers revealed by
total internal reflection fluorescence microscopy.
AB - Amyloid fibrils are fibrillar aggregates of denatured proteins associated with a
large number of amyloidoses. The formation of amyloid fibrils has been considered
to occur by nucleation and elongation. Real-time imaging of the elongation as
well as linear morphology of amyloid fibrils suggests that all elongation events
occur at the growing ends of fibrils. On the other hand, we suggested that
monomers also bind to the lateral sides of preformed fibrils during the seed
dependent elongation, diffuse to the growing ends, and finally make further
conformation changes to the mature amyloid fibrils. To examine lateral binding
during the elongation of fibrils, we used islet amyloid polypeptide (IAPP), which
has been associated with type II diabetes, and prepared IAPP modified with the
fluorescence dye, Alexa532. By monitoring the elongation process with amyloid
specific thioflavin T and Alexa532 fluorescence, we obtained overlapping images
of the two fluorescence probes, which indicated lateral binding. These results
are similar to the surface diffusion-dependent growth of crystals, further
supporting the similarities between amyloid fibrillation and the crystallization
of substances.
PMID- 25125373
TI - pH-dependent antigen-binding antibodies as a novel therapeutic modality.
AB - Monoclonal antibodies have become a general modality in therapeutic development.
However, even with infinite binding affinity to an antigen, a conventional
antibody is limited in that it can bind to the antigen only once, and this
results in antigen-mediated antibody clearance when the a membrane-bound antigen
is targeted, or in antibody-mediated antigen accumulation when a soluble antigen
is targeted. Recently, a pH-dependent antigen-binding antibody that binds to an
antigen in plasma at neutral pH and dissociates from the antigen in endosome at
acidic pH has been reported to overcome this limitation and to reduce antigen
mediated antibody clearance and antibody-mediated antigen accumulation. A pH
dependent binding antibody against a soluble antigen can be further improved by
Fc engineering to enhance the Fc receptor binding. Various approaches, including
histidine-based engineering, direct cloning from immunized animals, and synthetic
and combinatorial libraries, have been successfully applied to generate pH
dependent binding antibodies against various antigens. This review discusses the
features, approaches, advantages, and challenges of developing a pH-dependent
binding antibody as a novel therapeutic modality. This article is part of a
Special Issue entitled: Recent advances in molecular engineering of antibody.
PMID- 25125368
TI - A new look at social support: a theoretical perspective on thriving through
relationships.
AB - Close and caring relationships are undeniably linked to health and well-being at
all stages in the life span. Yet the specific pathways through which close
relationships promote optimal well-being are not well understood. In this
article, we present a model of thriving through relationships to provide a
theoretical foundation for identifying the specific interpersonal processes that
underlie the effects of close relationships on thriving. This model highlights
two life contexts through which people may potentially thrive (coping
successfully with life's adversities and actively pursuing life opportunities for
growth and development), it proposes two relational support functions that are
fundamental to the experience of thriving in each life context, and it identifies
mediators through which relational support is likely to have long-term effects on
thriving. This perspective highlights the need for researchers to take a new look
at social support by conceptualizing it as an interpersonal process with a focus
on thriving.
PMID- 25125374
TI - Effectiveness of laser Doppler perfusion monitoring in the assessment of
microvascular function in patients undergoing on-pump coronary artery bypass
grafting.
AB - OBJECTIVES: To evaluate the effectiveness of single-point laser Doppler perfusion
monitoring (LDPM) in the assessment of microvascular reactivity in the skin
during cardiopulmonary bypass (CPB). DESIGN: Cross-sectional observational study.
SETTING: Government-affiliated teaching hospital. PARTICIPANTS: Twenty male
patients aged 60 +/- 2 years who underwent coronary artery bypass grafting under
CPB. INTERVENTIONS: The authors assessed the endothelium-dependent vasodilation
of the skin microcirculation at the forehead and forearm using LDPM coupled with
thermal hyperemia. This measurement was performed before and after the induction
of anesthesia, during and after CPB, and 24 h after the end of the surgical
procedure. RESULTS: The basal values of microvascular flow before the induction
of anesthesia were significantly higher in the skin of the forehead compared with
that of the forearm. There were no significant alterations in microvascular
reactivity throughout the recording periods for both recording sites, as assessed
by the vasodilation range expressed as cutaneous vascular conductance (arbitrary
perfusion units/mean arterial pressure). CONCLUSIONS: Using LDPM, the authors
showed that the microcirculatory bed of the skin of the forehead, which is
readily accessible during cardiac surgery, is a suitable model for the study of
microvascular reactivity and tissue perfusion in cardiovascular surgical
procedures using CPB. This technique could, thus, be suitable for evaluating the
effects of drugs or technical procedures on tissue perfusion during cardiac
surgery under cardiopulmonary bypass.
PMID- 25125375
TI - Influence of light curing units and fluoride mouthrinse on morphological surface
and color stability of a nanofilled composite resin.
AB - Composite resin is a dental material susceptible to color change over time which
limits the longevity of restorations made with this material. The influence of
light curing units and different fluoride mouthrinses on superficial morphology
and color stability of a nanofilled composite resin was evaluated. Specimens (N =
150) were prepared and polished. The experimental groups were divided according
to the type of light source (halogen and LED) and immersion media (artificial
saliva, 0.05% sodium fluoride solution-manipulated, Fluordent Reach, Oral B,
Fluorgard). Specimens remained in artificial saliva for 24-h baseline. For 60
days, they were immersed in solutions for 1 min. Color readout was taken at
baseline and after 60 days of immersion. Surface morphology was analyzed by
Scanning Electron Microscopy (SEM) after 60 days of immersion. Color change data
were submitted to two-way Analysis of Variance and Tukey tests (alpha = 0.05).
Surface morphology was qualitatively analyzed. The factor light source presented
no significant variability (P = 0.281), the immersion media, significant
variability (P < 0.001) and interaction between factors, no significant
variability (P = 0.050). According to SEM observations, no difference was noted
in the surface of the specimens polymerized by different light sources,
irrespective of the immersion medium. It was concluded that the light source did
not influence the color stability of composite, irrespective of the immersion
media, and among the fluoride solutions analyzed, Fluorgard was the one that
promoted the greatest color change, however, this was not clinically perceptible.
The immersion media did not influence the morphology of the studied resin.
PMID- 25125377
TI - Santiago Ramon y Cajal: The Cajal Institute and the Spanish Histological School.
AB - Santiago Ramon y Cajal was a self-taught researcher. He almost always worked
alone, usually in the solitude of his private laboratory installed at his home.
He was also a university professor and therefore taught histology and pathology
to many students. But because research laboratories were scarce and poorly
equipped, he preferred to organize courses and tutor at home as well. For this
reason, Cajal left a faint trace of disciples in the three academic chairs that
he came to occupy. It may be argued that Cajal formed the histological school
when the Spanish government decided to support his investigations and created a
scientific laboratory for him, with funding to cover the cost of journals,
instruments, materials, personnel, and so forth. This support occurred in the
year 1902, after Cajal received the Moscow Prize. Some of his former students
accompanied Cajal to the new laboratory. Upon receipt of new awards, including
the Gold Medal of von Helmholtz (1905) and the Nobel Prize in Physiology or
Medicine (1906), Cajal's popularity increased and a large number of students
wanted to learn about the laboratory and work with the great Cajal. This review
tells this history. But we realize that this is not an easy task because to be
fair to all the people that formed the Spanish Histological School, we would need
to write a book. This is not practical. Instead, selection of contributors to the
formation of the Spanish Histological School is provided. At the same time, some
brushstrokes of the story extend to and include the Cajal Institute, which ran in
parallel with the Spanish Histological School.
PMID- 25125378
TI - Impact of environmental and personality factors upon adolescents before and after
psychotherapeutic intervention.
AB - It is important to understand the risk factors and resilience factors that
contribute to psychological distress or to a sense of well-being in adolescents.
This study focuses on life events and social support from an external
environmental aspect. The focus from an internal-personality aspect is on self
criticism and self-disclosure. In this study, 155 adolescents, ages 12-18 years,
were divided into two groups. The experimental group included 70 adolescents
requesting psychotherapy for emotional disorders. The control group included 85
adolescents without emotional disorders. Participants in the experimental group
were followed up to the completion of six months of psychotherapy. Adolescents in
the experimental group had undergone more negative life events and a
significantly smaller number of positive life events compared to the control
group [F(4, 143)=9.77, p<0.001, Eta(2)=.22]. The experimental group was
characterized by a diminished degree of social support compared to the control
group [F(2, 144)=7.27, p<0.01, Eta(2)=.09]. Regarding self-criticism and self
disclosure, no differences were found between the control and experimental groups
[F(3, 148)=2.18, p>0.05, Eta(2)=.04]. The prospective analysis following six
months of psychotherapy indicated a significant improvement in distress variables
reported by the parents but not by the subjects themselves, pointing to the
importance of family intervention as part of adolescent psychotherapy. A decrease
in the level of self-criticism after psychotherapeutic intervention was found
[F(1, 18)=4.41, p<0.05, Eta(2)=.20], altering self-criticism from a factor that
needs to be neutralized to a factor that can be improved during psychotherapy.
PMID- 25125376
TI - Functional chromatography reveals three natural products that target the same
protein with distinct mechanisms of action.
AB - Access to lead compounds with defined molecular targets continues to be a barrier
to the translation of natural product resources. As a solution, we developed a
system that uses discrete, recombinant proteins as the vehicles for natural
product isolation. Here, we describe the use of this functional chromatographic
method to identify natural products that bind to the AAA+ chaperone, p97, a
promising cancer target. Application of this method to a panel of fungal and
plant extracts identified rheoemodin, 1-hydroxydehydroherbarin, and
phomapyrrolidone A as distinct p97 modulators. Excitingly, each of these
molecules displayed a unique mechanism of p97 modulation. This discovery provides
strong support for the application of functional chromatography to the discovery
of protein modulators that would likely escape traditional high-throughput or
phenotypic screening platforms.
PMID- 25125379
TI - Diagnostic and clinical characteristics of early-manifesting females with
Duchenne or Becker muscular dystrophy.
AB - Manifestations of Duchenne and Becker muscular dystrophy (DBMD) are present in up
to 40% of heterozygous females, but there are few reports of females who exhibit
skeletal muscle symptoms in childhood. From the Muscular Dystrophy Surveillance
Tracking and Research Network, a multi-site population-based surveillance network
for dystrophinopathy, nine symptomatic female heterozygotes with onset of
symptoms prior to age 9 years were identified. The median age at diagnosis was
8.3 years, and the median interval from first symptoms to diagnosis was 1.35
years. Of the nine female heterozygotes, four had a positive family history,
seven had intellectual disability and five had at least one mental health
disorder. Mental health concerns included attention deficit hyperactivity
disorder (ADHD), autism spectrum features, bipolar disorder, and depression. The
frequency of intellectual and mental health problems in this group is higher than
previously reported for affected males and for symptomatic females. These
findings may have implications for diagnosis of early manifesting heterozygotes
and for their health supervision.
PMID- 25125380
TI - Injury to the suprascapular nerve during superior labrum anterior and posterior
repair: is a rotator interval portal safer than an anterosuperior portal?
AB - PURPOSE: The purpose of this study was to compare the risk of injury to the
suprascapular nerve during suture anchor placement in the glenoid when using an
anterosuperior portal versus a rotator interval portal. METHODS: Ten bilateral
fresh human cadaveric shoulders were randomized to anchor placement through the
anterosuperior portal on one shoulder and the rotator interval portal on the
contralateral shoulder. Standard 3 * 14 mm suture anchors were placed in the
glenoid rim (1 o'clock, 11 o'clock, and 10 o'clock positions for the right
shoulder). The suprascapular nerve was dissected. When glenoid perforation
occurred, the distance from the anchor tip to the suprascapular nerve, the
distance from the glenoid rim to the suprascapular nerve, and the drill-hole
depth at each entry site were recorded. RESULTS: All far-posterior anchors
perforated the glenoid rim when using the anterosuperior or rotator interval
portal. The distance from the far-posterior anchor tip to the suprascapular nerve
averaged 8 mm (range, 3.4 to 14 mm) for the anterosuperior portal and 2.1 mm
(range, 0 to 5.5 mm) for the rotator interval portal (P <= .001). CONCLUSIONS:
Using an anterosuperior or rotator interval portal results in consistent
penetration of 1 o'clock and 2 o'clock posterior anchors and might place the
suprascapular nerve at risk of iatrogenic injury. Based on closer proximity of
the anchor tip to the suprascapular nerve, the risk of injury is significantly
greater with a rotator interval portal. CLINICAL RELEVANCE: Using a rotator
interval portal for suture anchor placement in the posterior aspect of the
glenoid rim can lead to a higher likelihood of suprascapular nerve injury.
PMID- 25125381
TI - Ligamentum teres injuries of the hip: a systematic review examining surgical
indications, treatment options, and outcomes.
AB - PURPOSE: Hip arthroscopy is becoming a common technique for the diagnosis and
treatment of ligamentum teres pathologic conditions. This systematic review aims
to determine the indications/contraindications, treatments, and surgical outcomes
for management of ligamentum teres injuries. METHODS: We searched EMBASE,
MEDLINE, and PubMed databases from 1946 to November 28, 2013 for all relevant
English articles pertaining to surgical treatment of the ligamentum teres. A hand
search of the reference sections of included articles was performed, and all
relevant articles were systematically screened in duplicate, with agreement and
descriptive statistics presented. RESULTS: We identified 1,016 studies, 9 of
which (4 case series and 5 case reports) met our eligibility criteria. These
studies had a total of 87 patients (89 hips) who had undergone either
arthroscopic debridement (81 patients, 83 hips) or reconstruction with
autografting, allografting, or synthetic grafting (6 patients) of a torn
ligamentum teres. Major qualifications for surgery included persistent hip pain
despite conservative treatment and mechanical symptoms or instability symptoms
(e.g., clicking or locking). Advanced arthritis (i.e., radiographic joint space <
2 mm) was the only reported contraindication. Patients were followed
postoperatively for 1.5 to 60 months and were assessed using subjective methods
(i.e., modified Harris Hip Score [mHHS] and Non-Arthritic Hip Score [NAHS]).
Overall, both debridement and reconstruction improved the condition of patients,
with a 40% increase in reported postoperative functional scores as well as a
reported 89% of patients who were able to return to regular activity/sport.
CONCLUSIONS: Ligamentum teres debridement is indicated for short-term relief of
hip pain caused by partial-thickness tears (type 2) failing conservative
management, whereas reconstruction with autografts, allografts, or synthetic
grafts may be indicated for type 1 (full-thickness) ligamentum teres tears that
are deemed "reparable," cause instability, have failed previous debridement, or a
combination of these conditions. LEVEL OF EVIDENCE: Level IV, systematic review
of Level IV and Level V studies.
PMID- 25125382
TI - Arthroscopy-assisted surgery for tibial plateau fractures.
AB - PURPOSE: This study aimed to summarize the recent clinical outcomes of patients
undergoing arthroscopy-assisted reduction and internal fixation (ARIF) for tibial
plateau fractures. METHODS: A systematic electronic search of the PubMed and
Cochrane databases was performed in January 2014. All English-language clinical
studies on tibial plateau fractures treated with ARIF that were published after
January 1, 2000 were eligible for inclusion. Basic information related to the
surgery was collected. RESULTS: The search criteria initially identified 141
articles, and 19 studies were included in this systematic review. There were 2
retrospective comparative studies, 16 case series studies, and one clinical
series based on a technique note. There were a total of 609 patients in this
systematic review, with a mean follow-up time of 52.5 months. The most common
fracture types were Schatzker types II and III. Concomitant injuries were common:
42.2% of the patients had meniscal injuries, and 21.3% had anterior cruciate
ligament (ACL) injuries. In addition, the status of 90.5% of the patients was
classified as good or excellent according to the clinical Rasmussen scoring
system, and 90.9% of the patients were satisfied with the treatment. Only 6
severe complications were reported, including one case of compartment syndrome.
CONCLUSIONS: ARIF is a reliable, effective, and safe method for the treatment of
tibial plateau fractures, especially when they present with concomitant injuries.
LEVEL OF EVIDENCE: Level IV, systematic review of Level III and Level IV studies.
PMID- 25125385
TI - Hydroxychloroquine's Efficacy as an Antiplatelet Agent Study in Healthy
Volunteers: A Proof of Concept Study.
AB - BACKGROUND: With the inflammatory model of atherosclerosis taking center stage,
anti-inflammatory drugs hold a promising place in the therapy of cardiovascular
disease (CVD). Recent studies showed that hydroxychloroquine (HCQ) was protective
against thrombovascular events in lupus erythematosus and traditional
cardiovascular risk factors in patients with rheumatoid arthritis. Some
preliminary experimental data have shown that it may prevent platelet activation
too. OBJECTIVE: To evaluate the antiplatelet activity of HCQ when given alone and
in combination with aspirin (ASA) and compare it with ASA alone and ASA plus
clopidogrel (CLOP) in healthy human volunteers. METHODS: In part 1 of the study,
8 volunteers were given HCQ for 7 days. In part 2, 12 volunteers were randomly
assigned in a 1:1:1 ratio to the 3 groups in which 2 of the 3 treatments, ASA,
ASA plus CLOP, and ASA plus HCQ, were given in the 2 treatment periods separated
by a 14-day washout period using the incomplete block design. Inhibition of
platelet aggregation (IPA) was measured by light transmission aggregometry.
RESULTS: When arachidonic acid (AA) was used as agonist, HCQ given alone showed a
significant reduction in platelet aggregation (11.0% +/- 4.2%, P = .03). The IPA
was significantly increased when ASA plus HCQ was compared with ASA alone (31.2%
+/- 8.1%, P = .002). This synergistic effect was not seen with adenosine
diphosphate and collagen as agonists. Levels of serum 11-dehydrothromboxane B2, a
stable marker of thromboxane A2 production, were not significantly different
between the groups. There was also a significant decrease in fibrinogen and
erythrocyte sedimentation rate values when HCQ was used alone or in combination
with ASA. CONCLUSION: This study suggests that HCQ has antiplatelet properties
possibly through the AA pathway (downstream to thromboxane A2 production). With
possible additional beneficial effects over the traditional CVD risk factors,
larger studies in the future might explore HCQ's potential as an antiplatelet
agent.
PMID- 25125383
TI - Detection of C3d-binding donor-specific anti-HLA antibodies at diagnosis of
humoral rejection predicts renal graft loss.
AB - Antibody-mediated rejection (AMR) is a major cause of kidney graft loss, yet
assessment of individual risk at diagnosis is impeded by the lack of a reliable
prognosis assay. Here, we tested whether the capacity of anti-HLA antibodies to
bind complement components allows accurate risk stratification at the time of AMR
diagnosis. Among 938 kidney transplant recipients for whom a graft biopsy was
performed between 2004 and 2012 at the Lyon University Hospitals, 69 fulfilled
the diagnosis criteria for AMR and were enrolled. Sera banked at the time of the
biopsy were screened for the presence of donor-specific anti-HLA antibodies
(DSAs) and their ability to bind C1q and C3d using flow bead assays. In contrast
with C4d graft deposition, the presence of C3d-binding DSA was associated with a
higher risk of graft loss (P<0.001). Despite similar trend, the difference did
not reach significance with a C1q-binding assay (P=0.06). The prognostic value of
a C3d-binding assay was further confirmed in an independent cohort of 39 patients
with AMR (P=0.04). Patients with C3d-binding antibodies had worse eGFR and higher
DSA mean fluorescence intensity. In a multivariate analysis, only eGFR <30 ml/min
per 1.73 m(2) (hazard ratio [HR], 3.56; 95% confidence interval [CI], 1.46 to
8.70; P=0.005) and the presence of circulating C3d-binding DSA (HR, 2.80; 95% CI,
1.12 to 6.95; P=0.03) were independent predictors for allograft loss at AMR
diagnosis. We conclude that assessment of the C3d-binding capacity of DSA at the
time of AMR diagnosis allows for identification of patients at risk for allograft
loss.
PMID- 25125384
TI - Sex differences and attitudes toward living donor kidney transplantation among
urban black patients on hemodialysis.
AB - BACKGROUND AND OBJECTIVES: Living donor kidney transplantation, the treatment of
choice for ESRD, is underused by women and blacks. To better understand sex
differences in the context of potential barriers to living donor kidney
transplantation, the Dialysis Patient Transplant Questionnaire was administered
in two urban, predominantly black hemodialysis units. DESIGN, SETTING,
PARTICIPANTS, & MEASUREMENTS: The Dialysis Patient Transplant Questionnaire was
designed to study barriers to kidney transplantation from previously validated
questions. Between July of 2008 and January of 2009, the Dialysis Patient
Transplant Questionnaire was administered to 116 patients on hemodialysis,
including potentially eligible and ineligible living donor kidney transplantation
candidates. Of 101 patients who self-identified as black or African American, 50
(49.5%) patients had the questionnaire entirely administered by the researcher or
assistant, 25 (24.8%) patients required some assistance, and 26 (25.7%) patients
completed the Dialysis Patient Transplant Questionnaire entirely by themselves.
Multiple logistic regression methods were used to determine if the observed
bivariate associations and differences persisted when controlled for potential
confounders. RESULTS: Women were less likely to want living donor kidney
transplantation compared with men (58.5% versus 87.5%, P=0.003), despite being
nearly two times as likely as men to receive unsolicited offers for kidney
transplant (73.2% versus 43.2%, P=0.02). They were also less likely to have been
evaluated for a kidney transplant (28.3% versus 52.2%, P=0.01). The multiple
logistic regression analysis showed that sex was a statistically significant
predictor of wanting living donor kidney transplantation (women versus men odds
ratio, 0.13; 95% confidence interval, 0.04 to 0.46), controlling for various
factors known to influence transplant decisions. A sensitivity analysis indicated
that mode of administration did not bias these results. CONCLUSIONS: In contrast
to previous studies, the study found that black women were less likely to want
living donor kidney transplantation compared with black men. Black women were
also less likely to be evaluated for a kidney transplant, although they were more
likely to receive an unsolicited living donor kidney transplantation offer.
PMID- 25125387
TI - East Kent trust is placed in special measures after being rated inadequate.
PMID- 25125386
TI - Comparison of referrals for lumbar spine magnetic resonance imaging from
physiotherapists, primary care and secondary care: how should referral pathways
be optimised?
AB - OBJECTIVE: To compare sensitivity of pathology on imaging between referrals from
primary care, physiotherapists, spinal surgeons and other secondary care
providers. DESIGN AND SETTING: A retrospective review of 200 consecutive magnetic
resonance imaging (MRI) scans of patients' first presentations to radiology for
MR lumbar scanning at a tertiary orthopaedic centre. A scan report was defined as
positive if there was any evidence of neural compromise. Fisher's exact 2*2
contingency analyses were performed. RESULTS: Eighty-seven (44%) scans were
positive and 113 (57%) were negative. Forty-four percent of scans requested by
general practitioners (GPs) were reported as positive compared with 57% of scans
requested by physiotherapists. Only 40% and 20% of scans requested by specialist
spinal surgeons and non-spinal team secondary care providers were positive,
respectively. Physiotherapist referrals for MRI lumbar spine scans were
significantly more likely to be positive compared with GPs (P=0.05), spinal
surgeons (P=0.03) and others (P=0.004). CONCLUSION: When appropriate, referrals
via the extended physiotherapy service should be encouraged, rather than
referrals directly from GPs. With appropriate training and in the appropriate
clinical context, extended physiotherapy services could include inpatients and
could accept outpatient referrals from other secondary care providers and not
just from GPs; this would improve efficiency and reduce the workload of the
radiology department and the spinal surgical unit.
PMID- 25125388
TI - G-protein alphaq participates in the steroid hormone 20-hydroxyecdysone
nongenomic signal transduction.
AB - The nuclear receptor-mediated genomic pathways of the animal steroid hormones are
well known. However, the cell membrane receptor-mediated nongenomic pathways of
the animal steroid hormones are little understood. In this study, we report the
participation of a G-protein alpha q (Galphaq)(1) subunit in the 20E nongenomic
pathway in the cell membrane and regulating gene expression during molting and
metamorphosis in a lepidopteran insect, Helicoverpa armigera. 20E-induced
phosphorylation of Galphaq was detected using two-dimensional electrophoresis
techniques. Knockdown of Galphaq by injecting double-stranded RNA suppressed the
development of larvae, delayed metamorphosis, and inhibited 20E-induced gene
expression. Galphaq was distributed throughout the cell, and migrated toward the
plasma membrane upon 20E induction. Galphaq was necessary in the 20E-induced
intracellular Ca(2+) release and extracellular Ca(2+) influx. The protein kinase
C (PKC) inhibitor could repress 20E-induced phosphorylation of cyclin-dependent
kinase 10 (CDK10) and transcription factor ultraspiracle (USP1). PKC inhibitor
could repress the Galphaq phosphorylation and membrane trafficking. These results
suggest that Galphaq participates in 20E signaling in the cell membrane at the
pre-genomic stage by modulating the increase of the intracellular Ca(2+) and
phosphorylation of CDK10 and USP1 in 20E transcription complex to regulate gene
transcription.
PMID- 25125389
TI - DHEA - a precursor of ERbeta ligands.
AB - What is DHEA and why is there so much public interest in this steroid which has
been touted as the fountain of youth and is supposed to have all kinds of health
benefits? Endocrinologists have been fascinated with DHEA for a long time because
of its high production in the fetal adrenals and its continued high levels until
the 7th decade of life. Yet there is still little agreement about its
physiological functions. In its simplest terms endocrinology is the communication
between at least three organs: one sends a message, one releases a hormone into
the blood in response to the message and one responds to the hormone. DHEA is
produced by a specific zone of the adrenal cortex, the zona reticularis, whose
sole function is to produce this steroid. Glucocorticoids and mineralocorticoids
which are C21 steroids are produced in two other zones of the adrenal cortex
called the zona fasicularis and the zona glomerulosa, respectively. Being C21
steroids, they cannot be synthesized from DHEA which is a C19 steroid. To date
there is no known hormone which specifically stimulates the zona reticularis and
there is no known specific receptor for DHEA. Thus DHEA does not qualify as a
hormone. DHEA could have autocrine or paracrine effects but, so far, there is no
known effect of DHEA on either the cells of the zona glomerulosa or the zona
fasicularis. Of course DHEA could have functions as a local precursor of
androgens or estrogens and many studies have reported on the beneficial effects
of transdermal or transvaginal administration of DHEA in postmenopausal women.
This review will consider two of the potential functions of DHEA as a precursor
of estrogen receptor beta (ERbeta) ligands.
PMID- 25125390
TI - Testosterone decreases fluid and chloride secretions in the uterus of adult
female rats via down-regulating cystic fibrosis transmembrane regulator (CFTR)
expression and functional activity.
AB - OBJECTIVES: Estrogen is known to stimulate uterine fluid and Cl(-) secretion via
CFTR. This study investigated testosterone effect on these changes in a rat
model. METHODS: Ovariectomized adult female rats received estrogen for five days
or estrogen for three days followed by two days peanut oil or testosterone either
alone or in the presence of flutamide or finasteride. At the end of treatment,
uteri were perfused with perfusate containing CFTRinh-172. The rate of fluid and
Cl(-) secretion were determined. Dose-dependent effect of testosterone and effect
of forskolin on fluid secretion rate were measured. Animals were sacrificed and
uteri were removed for CFTR protein and mRNA expression analyses, histology and
cAMP measurement. Morphology of uterus, levels of expression of CFTR protein and
mRNA and distribution of CFTR protein were observed. RESULTS: Estrogen causes
increase while testosterone causes decrease in uterine fluid and Cl(-)
secretions. The effects of estrogen but not testosterone were antagonized by
CFTRinh-172. Luminal fluid volume and apical expression of CFTR in the luminal
epithelia were highest under estrogen and lowest under testosterone influences.
Similar changes were observed in CFTR protein and mRNA expressions. Uterine cAMP
level was highest under estrogen and lowest under testosterone influence.
Forskolin increases fluid secretion rate in estrogen but not in testosterone
treated animals. Testosterone effects were dose-dependent and were antagonized by
flutamide however, not finasteride. CONCLUSIONS: Testosterone inhibition of
estrogen-induced uterine fluid and Cl(-) secretion occurs via inhibition of CFTR
expression and functional activities. These changes could explain the adverse
effects of testosterone on fertility.
PMID- 25125391
TI - Assessment of psychiatric disorders among sex offenders: Prevalence and
associations with criminal history.
AB - BACKGROUND: Much of the research on the prevalence of psychiatric disorders among
sex offenders has been conducted in the USA or Europe. Less is known about it in
other regions, particularly in Asia. AIMS: The objective of this study is to
determine the prevalence of psychiatric disorders among sex offenders in Taiwan
and their associations with offender characteristics and criminal history.
METHODS: Participants were randomly selected from men serving sentences in
Taiwan's prison for serious sex offenders. Consenting men were assessed using the
structured clinical interviews for DSM-IV-TR Axis I and II disorders.
Demographics and criminal history were also recorded. RESULTS: Over two-thirds of
the 68 participants met criteria for one or more lifetime Axis I disorders, and
nearly 60% met criteria for one or more Axis II disorder. The higher the number
of Axis I and cluster B personality disorders, the higher was the total number of
convictions. CONCLUSIONS: Our study adds to the literature that suggests that
psychiatric assessment is likely to have an important role in the management and
treatment of sex offenders. The finding that multiple disorders are common in
this group and associated with more convictions for sex offences suggests that
failure to include psychiatric assessment in planning the management of sex
offenders may increase the risk of recidivism.
PMID- 25125393
TI - Fertility-sparing management combined with photodynamic therapy for endometrial
stromal sarcoma: a case report.
AB - BACKGROUND AND OBJECTIVES: Low-grade endometrial sarcoma (LGESS) has a favorable
prognosis after standard surgical treatment. The conservative fertility-sparing
treatments in young patients with LGESS have been reported; however, the role of
conservative therapy is not well defined. STUDY DESIGN/PATIENT AND METHODS: A 31
year-old nulliparous woman was diagnosed with LGESS after resection of a cervical
polyp with resection margin positive for malignancy. She underwent fertility
sparing surgery including laparoscopic pelvic lymph node dissection,
hysteroscopic endometrial polypectomy, endocervical curettage, and photodynamic
therapy (PDT) on the endometrium and uterine cervix. And she had received
adjuvant therapy with a non-steroidal aromatase inhibitor. RESULTS: She conceived
by in vitro fertilization and delivered twins at 32+2 weeks gestation by Cesarean
section 32 months after conservative treatment. She has no evidence of recurrence
after 99 months of follow-up. CONCLUSION: Conservative management of LGESS may be
attempted in selected patients who want to preserve fertility. Conservative
surgery combined with PDT has shown effective results in long-term follow-up.
PMID- 25125392
TI - Cumulative dietary exposure to a selected group of pesticides of the triazole
group in different European countries according to the EFSA guidance on
probabilistic modelling.
AB - The practicality was examined of performing a cumulative dietary exposure
assessment according to the requirements of the EFSA guidance on probabilistic
modelling. For this the acute and chronic cumulative exposure to triazole
pesticides was estimated using national food consumption and monitoring data of
eight European countries. Both the acute and chronic cumulative dietary exposures
were calculated according to two model runs (optimistic and pessimistic) as
recommended in the EFSA guidance. The exposures obtained with these model runs
differed substantially for all countries, with the highest exposures obtained
with the pessimistic model run. In this model run, animal commodities including
cattle milk and different meat types, entered in the exposure calculations at the
level of the maximum residue limit (MRL), contributed most to the exposure. We
conclude that application of the optimistic model run on a routine basis for
cumulative assessments is feasible. The pessimistic model run is laborious and
the exposure results could be too far from reality. More experience with this
approach is needed to stimulate the discussion of the feasibility of all the
requirements, especially the inclusion of MRLs of animal commodities which seem
to result in unrealistic conclusions regarding their contribution to the dietary
exposure.
PMID- 25125394
TI - The development of a high-throughput measurement method of octanol/water
distribution coefficient based on hollow fiber membrane solvent microextraction
technique.
AB - This paper describes the development of a novel high-throughput hollow fiber
membrane solvent microextraction technique for the simultaneous measurement of
the octanol/water distribution coefficient (logD) for organic compounds such as
drugs. The method is based on a designed system, which consists of a 96-well
plate modified with 96 hollow fiber membrane tubes and a matching lid with 96
center holes and 96 side holes distributing in 96 grids. Each center hole was
glued with a sealed on one end hollow fiber membrane tube, which is used to
separate the aqueous phase from the octanol phase. A needle, such as microsyringe
or automatic sampler, can be directly inserted into the membrane tube to deposit
octanol as the accepted phase or take out the mixture of the octanol and the
drug. Each side hole is filled with aqueous phase and could freely take in/out
solvent as the donor phase from the outside of the hollow fiber membranes. The
logD can be calculated by measuring the drug concentration in each phase after
extraction equilibrium. After a comprehensive comparison, the
polytetrafluoroethylene hollow fiber with the thickness of 210 MUm, an extraction
time of 300 min, a temperature of 25 degrees C and atmospheric pressure without
stirring are selected for the high throughput measurement. The correlation
coefficient of the linear fit of the logD values of five drugs determined by our
system to reference values is 0.9954, showed a nice accurate. The -8.9% intra-day
and -4.4% inter-day precision of logD for metronidazole indicates a good
precision. In addition, the logD values of eight drugs were simultaneously and
successfully measured, which indicated that the 96 throughput measure method of
logD value was accurate, precise, reliable and useful for high throughput
screening.
PMID- 25125395
TI - Simultaneous quantification of 5-hydroxyindoleacetic acid and 5-hydroxytryptamine
by capillary electrophoresis with quantum dot and horseradish peroxidase enhanced
chemiluminescence detection.
AB - A capillary electrophoresis (CE) with chemiluminescence (CL) detection method was
developed for the simultaneous quantification of 5-hydroxyindoleacetic acid (5
HIAA) and 5-hydroxytryptamine (5-HT). In this method, CdTe quantum dot (QD) and
horseradish peroxidase (HRP) were used as enhancing reagents to co-catalyze the
post-column CL reaction between luminol and hydrogen peroxide, achieving highly
efficient CL emission. 5-HIAA and 5-HT inhibit the CL emission resulting to the
formation of negative peaks in electropherogram. The degree of CL suppression is
proportional to the concentration of 5-HT and 5-HIAA. The linear ranges for the
determination of 5-HIAA and 5-HT were 2.5*10(-8)-2.5*10(-6) M and 2.5*10(-8)
5.0*10(-6) M with detection limits (signal/noise=3) of 7.0*10(-9) M and 6.0*10(
9) M, respectively. Intraday precision do not exceed 5.0%. The accuracy was
confirmed by the recoveries ranged from 98% to 104%. The present method was
successfully applied for the quantification of 5-HIAA and 5-HT in human urine.
The concentrations of 5-HT and 5-HIAA in human urine were found to be in the
range of 0.78-1.2 MUM and 3.2-5.1 MUM, respectively.
PMID- 25125396
TI - Overestimation of 25-hydroxyvitamin D3 by increased ionisation efficiency of 3
epi-25-hydroxyvitamin D3 in LC-MS/MS methods not separating both metabolites as
determined by an LC-MS/MS method for separate quantification of 25-hydroxyvitamin
D3, 3-epi-25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 in human serum.
AB - BACKGROUND: An LC-MS/MS method was developed for simultaneous quantification of
25-hydroxyvitamin D3 (25(OH)D3), 3-epi-25(OH)D3, and 25(OH)D2 in human serum.
METHODS: Sample preparation consisted of protein precipitation followed by off
line SPE. Calibration curves for each vitamin D metabolite were constructed in
phosphate-buffered saline with 60 g/L albumin including its corresponding stable
isotope labelled (SIL) internal standard. A pentafluorophenyl (PFP) analytical
column was used to resolve 25(OH)D3 from 25(OH)D2 and 3-epi-25(OH)D3, followed by
SRM registration using positive ESI-MS/MS. Accuracy was assessed from measurement
of samples with NIST reference method procedure (RMP) assigned values. The PFP LC
MS/MS method was compared to an in-house C18 column LC-MS/MS method, not
resolving 25(OH)D3 from 3-epi-25(OH)D3, using adult and newborn samples. RESULTS:
Intra-assay and inter-assay coefficients of variation were less than 4% and 7.5%,
respectively for all three vitamin D metabolites; lower limits of quantification
were 1, 1 and 2 nmol/L and linearity of methods were 1-500, 1-200 and 2-500
nmol/L for 25(OH)D3, 3-epi-25(OH)D3 and 25(OH)D2, respectively. The PFP LC-MS/MS
method showed minimal bias to the NIST RMP. Method comparison revealed that in
the C18 LC-MS/MS method, the 3-epi-25(OH)D3 concentration is overestimated
inadvertently not only from co-elution of both analytes, but also by an
additional 30-40% higher ionisation efficiency of 3-epi-25(OH)D3 when compared to
25(OH)D3. CONCLUSION: This accurate LC-MS/MS method allows the simultaneous
measurement of 25(OH)D3, 3-epi-25(OH)D3, and 25(OH)D2 in human serum. Due to
increased ionisation efficiency, the contribution of the 3-epi-25(OH)D3
metabolite to the total 25(OH)D3 concentration is significantly overestimated in
MS methods that do not resolve 3-epi-25(OH)D3 from 25(OH)D3 and may compromise
its use in infant samples known to have significant amounts of 3-epi-25(OH)D3.
PMID- 25125397
TI - Performance characterization of a quantitative liquid chromatography-tandem mass
spectrometric method for 12 macrolide and lincosamide antibiotics in salmon,
shrimp and tilapia.
AB - This paper describes an extension and performance characterization of a
quantitative confirmatory multi-residue liquid chromatography-tandem mass
spectrometric method for residues of macrolide and lincosamide antibiotics,
originally validated for application to bovine kidney tissues, to tissues of
salmon, shrimp and tilapia. The 12 analytes include clindamycin, erythromycin A,
gamithromycin, josamycin, lincomycin, neospiramycin 1, oleandomycin, pirlimycin,
spiramycin 1, tildipirosin, tilmicosin and tylosin A. The limit of detection was
0.5 MUg/kg. Within-laboratory precision evaluated over the analytical range of
5.0-50.0 MUg/kg ranged from 4 to 17%. The accuracy of the method ranged from 80
to 112%. Recoveries ranged from 47 to 99% with all but one recovery above 60%.
This is the first report of a quantitative confirmatory method for gamithromycin,
pirlimycin and tildipirosin in fish and shrimp.
PMID- 25125398
TI - Development of an LC-MS/MS method for high throughput quantification of metformin
uptake in transporter inhibition assays.
AB - A high throughput LC-MS/MS method for quantification of metformin substrate
uptake enables conversion of radiometric transporter inhibition assays for
multidrug and toxin extrusion transporters (MATE 1 and 2) and organic cation
transporter 2 (OCT2) to a nonradioactive format. Such conversion greatly
simplifies assay complexity and reduces assay costs. The development of a
quantitative LC-MS/MS method for metformin in support of the high throughput
transporter inhibition assays faced specific challenges of achieving both
adequate chromatographic retention and rapid analytical turnaround. Here we
report a method that circumvents both challenges. The utilization of a porous
graphitic carbon column (Hypercarb) ensured adequate retention of highly polar
metformin in biological samples. The combined employment of a ballistic gradient
on a 3 mm * 30 mm, 5 MUm Hypercarb column, and dual staggered chromatography
coupled with multiple injection chromatography acquisition, yielded a fast
injection-to-injection cycle time of 30s. The method demonstrated good accuracy,
precision and excellent robustness for high throughput applications, and has been
successfully implemented in the development and validation of the nonradioactive
transporter inhibition assays for MATEs and OCT2.
PMID- 25125400
TI - Treat sickest hepatitis C patients first, new US guidelines recommend.
PMID- 25125402
TI - Combined animal and plant health agency to be created.
PMID- 25125401
TI - EFSA assesses the impact of scrapie eradication policies.
PMID- 25125403
TI - FSA releases first results from Campylobacter survey.
PMID- 25125404
TI - Bristol academic recognised for contributions to feline medicine.
PMID- 25125405
TI - Celebrating success in statutory membership exam.
PMID- 25125406
TI - BVA steps up non-stun slaughter campaign.
PMID- 25125399
TI - Cargo sorting in the endocytic pathway: a key regulator of cell polarity and
tissue dynamics.
AB - The establishment and maintenance of polarized plasma membrane domains is
essential for cellular function and proper development of organisms. Epithelial
cells polarize along two fundamental axes, the apicobasal and the planar, both
depending on finely regulated protein trafficking mechanisms. Newly synthesized
proteins destined for either surface domain are processed along the biosynthetic
pathway and segregated into distinct subsets of transport carriers emanating from
the trans-Golgi network or endosomes. This exocytic trafficking has been
identified as essential for proper epithelial polarization. Accumulating evidence
now reveals that endocytosis and endocytic recycling play an equally important
role in epithelial polarization and the appropriate localization of key polarity
proteins. Here, we review recent work in metazoan systems illuminating the
connections between endocytosis, postendocytic trafficking, and cell polarity,
both apicobasal and planar, in the formation of differentiated epithelial cells,
and how these processes regulate tissue dynamics.
PMID- 25125407
TI - New partnership a first for the AWF.
PMID- 25125408
TI - Views sought on global standard for animal welfare in vet schools.
PMID- 25125409
TI - Private Members Bill proposes regulation of commercial cat breeding.
PMID- 25125410
TI - WSAVA advises on companion animal vaccination in Asia.
PMID- 25125411
TI - Helping farmers choose the best livestock for tropical climates.
PMID- 25125412
TI - FVE seeks views on recommendations for improving aquatic animal health.
PMID- 25125413
TI - 'Tour de Yorkshire' raises funds for Indian animal welfare charity.
PMID- 25125414
TI - MERS infection in animals to be reported as an emerging disease.
PMID- 25125415
TI - Responding to concerns about complaints.
AB - When the RCVS asked members of the profession and public about its complaints and
disciplinary system, it received a great deal of feedback - some positive, but
much of it critical. Here, Luke Bishop, RCVS communications officer, describes
how the process has now been overhauled with the aim of making it quicker, more
efficient and a more satisfactory experience for all involved.
PMID- 25125416
TI - Unusual cases of blackleg in cattle.
PMID- 25125417
TI - Impact of Schmallenberg virus on British farms.
PMID- 25125418
TI - Angiostrongylus vasorum infection in Cornwall.
PMID- 25125419
TI - PDSA to expand its charitable objects.
PMID- 25125420
TI - Fungal ingestion in companion animals.
PMID- 25125421
TI - A validation study of the Hong Kong version of Montreal Cognitive Assessment (HK
MoCA) in Chinese older adults in Hong Kong.
AB - OBJECTIVE: To validate the Hong Kong version of Montreal Cognitive Assessment (HK
MoCA) in identification of mild cognitive impairment and dementia in Chinese
older adults. DESIGN: Cross-sectional study. SETTING: Cognition clinic and memory
clinic of a public hospital in Hong Kong. PARTICIPANTS: A total of 272
participants (dementia, n=130; mild cognitive impairment, n=93; normal controls,
n=49) aged 60 years or above were assessed using HK-MoCA. The HK-MoCA scores were
validated against expert diagnosis according to the Diagnostic and Statistical
Manual of Mental Disorders (4th ed) criteria for dementia and Petersen's criteria
for mild cognitive impairment. Statistical analysis was performed using receiver
operating characteristic curve and regression analyses. Additionally, comparison
was made with the Cantonese version of Mini-Mental State Examination and Global
Deterioration Scale. RESULTS: The optimal cutoff score for the HK-MoCA to
differentiate cognitive impaired persons (mild cognitive impairment and dementia)
from normal controls was 21/22 after adjustment of education level, giving a
sensitivity of 0.928, specificity of 0.735, and area under the curve of 0.920.
Moreover, the cutoff to detect mild cognitive impairment was 21/22 with a
sensitivity of 0.828, specificity of 0.735, and area under the curve of 0.847.
Score of the Cantonese version of the Mini-Mental State Examination to detect
mild cognitive impairment was 26/27 with a sensitivity of 0.785, specificity of
0.816, and area under the curve of 0.857. At the optimal cutoff of 18/19, HK-MoCA
identified dementia from controls with a sensitivity of 0.923, specificity of
0.918, and area under the curve of 0.971. CONCLUSION: The HK-MoCA is a useful
cognitive screening instrument for use in Chinese older adults in Hong Kong. A
score of less than 22 should prompt further diagnostic assessment. It has
comparable sensitivity with the Cantonese version of Mini-Mental State
Examination for detection of mild cognitive impairment. It is brief and feasible
to conduct in the clinical setting, and can be completed in less than 15 minutes.
Thus, HK-MoCA provides an attractive alternative screening instrument to Mini
Mental State Examination which has ceiling effect (ie may fail to detect
mild/moderate cognitive impairment in people with high education level or
premorbid intelligence) and needs to be purchased due to copyright issues.
PMID- 25125422
TI - Investigation of availability and accessibility of community automated external
defibrillators in a territory in Hong Kong.
AB - OBJECTIVE: To evaluate the availability and accessibility of community automated
external defibrillators in a territory in Hong Kong. DESIGN: Cross-sectional
study. SETTING: Two public hospitals in New Territories West Cluster in Hong
Kong. PARTICIPANTS: Information about the locations of community automated
external defibrillators was obtained from automated external defibrillator
suppliers and through community search. Data on locations of out-of-hospital
cardiac arrests from August 2010 to September 2013 were obtained from the local
cardiac arrest registry of the emergency departments of two hospitals. Sites of
both automated external defibrillators and out-of-hospital cardiac arrests were
geographically coded and mapped. The number of out-of-hospital cardiac arrests
within 100 m of automated external defibrillators per year and the proportion of
out-of-hospital cardiac arrests with accessible automated external defibrillators
(100 m) were calculated. The number of community automated external
defibrillators per 10,000 population and public access defibrillation rate were
also calculated and compared with those in other countries. RESULTS: There were a
total of 207 community automated external defibrillators in the territory. The
number of automated external defibrillators per 10,000 population was 1.942. All
facilities with automated external defibrillators in this territory had more than
0.2 out-of-hospital cardiac arrests per automated external defibrillator per year
within 100 m. Among all out-of-hospital cardiac arrests, 25.2% could have an
automated external defibrillator reachable within 100 m. The public access
defibrillation rate was 0.168%. CONCLUSIONS: The number and accessibility of
community automated external defibrillators in this territory are comparable to
those in other developed countries. The placement site of community automated
external defibrillators is cost-effective. However, the public access
defibrillation rate is low.
PMID- 25125423
TI - Clinical applications of age-related macular degeneration genetics.
AB - Understanding genetic causes of age-related macular degeneration (AMD) will
eventually yield effective discoveries and improvements in predictive/prognostic
methods. These include, but are not limited to, reliable disease prediction
(screening for increased discrimination of clinical risk), differential
classification of AMD subtypes with biomarkers (development of risk-linked
molecular taxonomies), selection of optimal preventive and therapeutic
interventions (guided by a biologically meaningful understanding of treatment
response), and drug dosing. In this review, we discuss clinical applications
informed by key findings in AMD genetics, and provide commentary on leveraging
extant and forthcoming evidence to improve AMD risk prediction, AMD
classification, and knowledge on the genetic basis of drug activity and toxicity.
Advances in translating AMD genetics findings for AMD risk prediction require
development of a genetics-based causality for AMD incidence and progression.
Molecular subtyping of AMD phenotypes requires a set of dynamic biomarkers
presenting prognostic value; although these have yet to be identified, the
formation of multidisciplinary teams and their participation in large-scale
consortia may yield promising results. Drugs targeting complement and vascular
endothelial growth factor (VEGF) systems are under evaluation, and forthcoming
work on rare variants and noncoding DNA in AMD pathogenesis will likely reveal
biochemical pathways enriched with AMD-associated genetic variants. Pharmacologic
targets in these pathways may inform a rational and effective therapeutic
approach to preventing and treating this sight-threatening disease.
PMID- 25125426
TI - Early experience affects the strength of vigilance for threat in rhesus monkey
infants.
AB - Both human and nonhuman primates exhibit a cognitive bias to social threat, but
little is known about how this bias develops. We investigated the development of
threat bias in free-ranging infant rhesus macaques (Macaca mulatta) at 3 months
(n = 45) and 9 months (n = 46) of age. Three-month-olds did not display bias, but
9-month-olds exhibited increased maintenance of attention to threatening social
stimuli. To examine whether the social environment affected this increased
vigilance for threat, we collected behavioral data on maternal rank and
protectiveness across the first 12 weeks of life for infants tested at 9 months.
Among 9-month-olds, those of high-ranking and more protective mothers displayed
greater vigilance for threat than those of lower-ranking and less protective
mothers. These results demonstrate that infant social cognition is shaped by
mothers both directly (via protectiveness) and indirectly (through social rank).
PMID- 25125427
TI - Gaze following is accelerated in healthy preterm infants.
AB - Gaze following is an essential human communication cue that orients the attention
of two interacting people to the same external object. This capability is
robustly observed after 7 months of age in full-term infants. Do healthy preterm
infants benefit from their early exposure to face-to-face interactions with other
humans to acquire this capacity sooner than full-term infants of the same
chronological age, despite their immature brains? In two different experiments,
we demonstrated that 7-month-old preterm infants performed like 7-month-old full
term infants (with whom they shared the same chronological age) and not like 4
month-old full-term infants (with whom they shared the same postmenstrual age).
The duration of exposure to visual experience thus appears to have a greater
impact on the development of early gaze following than does postmenstrual age.
PMID- 25125424
TI - Lower urinary tract symptoms in men.
AB - Benign prostatic hyperplasia (BPH) is a highly prevalent and costly condition
that affects older men worldwide. Many affected men develop lower urinary tract
symptoms, which can have a negative impact on their quality of life. In the past,
transurethral resection of the prostate (TURP) was the mainstay of treatment.
However, several efficacious drug treatments have been developed, which have
transformed BPH from an acute surgical entity to a chronic medical condition.
Specifically, multiple clinical trials have shown that alpha adrenoceptor
antagonists can significantly ameliorate lower urinary tract symptoms. Moreover,
5alpha reductase inhibitors, alone or combined with an alpha adrenoceptor
antagonist, can reverse the natural course of BPH, reducing the risk of urinary
retention and the need for surgical intervention. Newer medical regimens
including the use of antimuscarinic agents or phosphodiesterase type 5
inhibitors, have shown promise in men with predominantly storage symptoms and
concomitant erectile dysfunction, respectively. For men who do not adequately
respond to conservative measures or pharmacotherapy, minimally invasive surgical
techniques (such as transurethral needle ablation, microwave thermotherapy, and
prostatic urethral lift) may be of benefit, although they lack the durability of
TURP. A variety of laser procedures have also been introduced, whose improved
hemostatic properties abrogate many of the complications associated with
traditional surgery.
PMID- 25125429
TI - [We can do better to prevent head injuries].
PMID- 25125428
TI - Perceiving crowd attention: ensemble perception of a crowd's gaze.
AB - In nearly every interpersonal encounter, people readily gather socio-visual cues
to guide their behavior. Intriguingly, social information is most effective in
directing behavior when it is perceived in crowds. For example, the shared gaze
of a crowd is more likely to direct attention than is a single person's gaze. Are
people equipped with mechanisms to perceive a crowd's gaze as an ensemble? Here,
we provide the first evidence that the visual system extracts a summary
representation of a crowd's attention; observers rapidly pooled information from
multiple crowd members to perceive the direction of a group's collective gaze.
This pooling occurred in high-level stages of visual processing, with gaze
perceived as a global-level combination of information from head and pupil
rotation. These findings reveal an important and efficient mechanism for
assessing crowd gaze, which could underlie the ability to perceive group
intentions, orchestrate joint attention, and guide behavior.
PMID- 25125430
TI - [Research at Landspitali University Hospital - comparison with the Nordic
countries and new opportunities].
PMID- 25125431
TI - [Visits to an emergency department due to head injuries].
AB - INTRODUCTION: Head injury is a common consequence of accidents and violence. It
can result in permanent disability and is one of the leading causes of premature
death worldwide. Our aim was to review all visits to Landspitali University
Hospital (LUH) from head injuries, to study the incidence, nature and severity of
head injuries. MATERIAL AND METHODS: A retrospective study on all visits of
Reykjavik's inhabitants to LUH for head injuries in the years 2000-2005 and 2008
2009. Data were collected from patient records at LUH. One main diagnosis was
used if head injury diagnoses were many. They were categorised into 5 groups;
soft tissue injury, eye injury, injury to cranium, intracranial- and cranial
nerve injury and multiple trauma. RESULTS: During the study period 35.031
patients presented with head injuries to LUH. Males were 67%. Mean age was 26
years (0-107). The highest rate was among infants and children aged 0-4 years
(20.8%), followed by 5-9 years (11,5%) and 20-24 years (9.4%). The annual
incidence decreased between the study periods from 4.2% to 3.3%. The annual
incidence for admitted head injury patients decreased from 181/year/100.000
inhabitants to 110/year/100.000 inhabitants. Most often injuries were caused by
accidents (80,5%) and violence (12.7%). Soft tissue injury was the most common
injury (65%), followed by eye injury (15%) and intracranial- and cranial nerve
injury (14%). The injuries that most frequently led to hospital admission were
intracranial bleeding (90.1%), followed by skull fracture (79.2%). CONCLUSION:
Accidents and violence caused most head injuries and they are more common among
men than women. Patients with intracranial haemorrhage were usually admitted.
Incidence of hospital visits and admissions because of head injuries in Reykjavik
has decreased over the last decade. Key words: Head injury, accident, violence,
brain injury, intracranial bleeding.
PMID- 25125432
TI - [Giant thymoma - case report].
AB - Thymomas are usually benign tumors and are most often found in the anterior
mediastinum. We report a rare case of a giant tumor in the right hemithorax that
originated in the thymus. The tumor was 15x8 cm and histology revealed a type AB
thymoma. The tumor was removed and the patient is doing well and is without
symptoms two years after the operation. Key words: Thymoma, abdominal pain, giant
tumor, mediastinum.
PMID- 25125433
TI - [We are only human - reflection on nurse prosecution].
PMID- 25125434
TI - ["Shame and blame" threatens patient safety].
PMID- 25125435
TI - [Needle exchange programs are a cost-effective preventative measure against HIV
in Iceland].
AB - OBJECTIVE: In 2007 there was a sudden increase in HIV cases among intravenous
drug users (IDUs) in Iceland. In 2007 - 2011 there were 34 new HIV cases among
IDUs compared to four in the previous four year period. The purpose of this study
was to assess whether needle exchange programs (NEPs) were cost-effective in
preventing the spread of HIV among IDUs in Iceland. MATERIALS AND METHODS: Cost
utility analysis was conducted from a societal perspective. Costs are presented
at the 2011 price level and values were discounted using a 3% discount rate. A
ten year period, 2011 - 2020 was compared with and without NEPs. The Incremental
Cost-Utility Ratio (ICUR) was calculated as societal cost per quality adjusted
life year (QALY). Sensitivity analysis was performed on study assumptions.
RESULTS: The estimated societal costs associated with HIV infections among IDUs
from 2011 - 2020 was 914.369.621 ISK without NEP and 947.653.758 ISK with NEP.
Excess societal cost due to NEP was 33.284.137 ISK. Societal utility from NEP was
7,39 QALYs. Additionally, NEP prevented 4-5 HIV infections. The ICUR of providing
NEP was 4.506.720 ISK. CONCLUSION: According to WHO an intervention is considered
cost-effective if the ICUR is less than three-fold national GDP per capita. In
2011 the GDP per capita in Iceland was 15.315.000 ISK. Sensitivity analysis on
study assumptions yielded a societal cost within the WHO limit. Therefore, the
results indicate that NEPs are cost-effective in preventing the spread of HIV
among IDUs in Iceland.
PMID- 25125436
TI - [Patient satisfaction with care and interaction with staff in the Acute Cardiac
Unit at Landspitali - The National University Hospital of Iceland].
AB - INTRODUCTION: The Icelandic health care system ranks favourably in international
comparison but patients' experience of interaction with the health service has
not been well studied. The goal of this study was to examine the satisfaction of
patients admitted to the Acute Cardiac Unit (ACU) at Landspitali - The National
University Hospital of Iceland. METHODS: A questionnaire based on the Patient
Satisfaction Questionnaire III was mailed to patients admitted to the ACU between
1 January and 29 February 2012. Questions were presented as statements and
participants asked to respond how strongly on a scale from 1 to 5 they agreed or
disagreed with each statement. Data analysis was performed using descriptive
statistics, Cronbach's alpha for internal consistency of scales and principal
components analysis, Wilcoxon-Mann-Whitney and Kruskal-Wallis tests for
comparison of groups and Pearson and Spearman correlation coefficients for
correlation between variables. RESULTS: The questionnaire was mailed to 485
individuals of whom 275 (57%) responded. The median age of the participants was
62 (range, 19-95) years and 132 (48%) were women. Internal consistency of the
scales was mostly high (Cronbach's alpha 0.62-0.91) and principal components
analysis revealed one main factor. The mean score of the questionnaire was 6.8 +/
1.0 and 91%, and 86% of the participants were pleased with their interaction with
physicians and nurses, respectively. Similarly, 88% were pleased with the care
they recieved but 25% felt they received insufficient explanations of their
symptoms or that follow-up care was lacking. CONCLUSION: Patients of the ACU
generally appear to be satisfied with their care. However, our results suggest
that improvement is needed in several areas, including information provided at
discharge and follow-up care.
PMID- 25125437
TI - [Cerebral ischemia/infarction - diagnosis and treatment].
AB - Four hundred individuals suffer from ischemic stroke every year in Iceland, more
than one daily. Cerebral ischemia is an emergency. Around two million brain cells
die every minute after an occlusion of a cerebral artery. Therefore, it is of
utmost importance that the patient is transported quickly to hospital, not least
to receive thrombolytic treatment. Even though thrombolytic treatment can be
given up to four and a half hours after the ictal event, time is brain and the
effect of thombolysis reduces dramatically as times passes. For every two
patients who are treated inside one hour, one recovers fully. When the treatment
is administred between three and four and a half hours only one in 14 recovers
fully. All patients with an acute stroke should be admitted to a stroke unit
where a multidisciplinary focus on stroke causation and treatment is present,
with emphasis on early rehabilitation. Secondary preventive treatment focusing on
anti-thrombotic, hypertensive, diabetic, cholesterol lowering treatment, carotic
endarterectomy and life style changes should be initiated as soon as possible.
PMID- 25125438
TI - Use patient power to tackle medical corruption in India.
PMID- 25125439
TI - A prospective interrupted time series study of interventions to improve the
quality, rating, framing and structure of goal-setting in community-based brain
injury rehabilitation.
AB - OBJECTIVE: To investigate whether the introduction of an electronic goals system
followed by staff training improved the quality, rating, framing and structure of
goals written by a community-based brain injury rehabilitation team. DESIGN:
Interrupted time series design. INTERVENTION: Two interventions were introduced
six months apart. The first intervention comprised the introduction of an
electronic goals system. The second intervention comprised a staff goal training
workshop. METHODS: An audit protocol was devised to evaluate the goals. A random
selection of goal statements from the 12 months prior to the interventions (Time
1 baseline) were compared with all goal statements written after the introduction
of the electronic goals system (Time 2) and staff training (Time 3). All goals
were de-identified for client and time-period, and randomly ordered. RESULTS: A
total of 745 goals (Time 1 n = 242; Time 2 n = 283; Time 3 n = 220) were
evaluated. Compared with baseline, the introduction of the electronic goals
system alone significantly increased goal rating, framing and structure (chi(2)
tests 144.7, 18.9, 48.1, respectively, p < 0.001). The addition of staff training
meant that the improvement in goal quality, which was only a trend at Time 2, was
statistically significant at Time 3 (chi(2) 15.0, p <= 001). The training also
led to a further significant increase in the framing and structuring of goals
over the electronic goals system (chi(2) 11.5, 12.5, respectively, p <= 0.001).
CONCLUSION: An electronic goals system combined with staff training improved the
quality, rating, framing and structure of goal statements.
PMID- 25125440
TI - Effectiveness of constraint-induced movement therapy on upper-extremity function
in children with cerebral palsy: a systematic review and meta-analysis of
randomized controlled trials.
AB - OBJECTIVE: To systematically examine the research literature on the effectiveness
of constraint-induced movement therapy on improving arm function in children with
cerebral palsy, and to assess the association between the study effect size and
the characteristics of the patients and intervention protocol. DATA SOURCES: A
systematic literature search was conducted in PubMed, PsycINFO, Cochrane, CINAHL,
Web of Science, and TRIP Database up to May 2014. REVIEW METHODS: Studies
employing randomized controlled trial design, children with cerebral palsy,
comparing constraint-induced movement therapy with another intervention with a
focus on arm function, and upper-extremity measures were included in this review.
Methodological quality was evaluated using the Physiotherapy Evidence-based
Database (PEDro) scale. RESULTS: The literature search resulted in 27 randomized
controlled trial studies with good methodological quality that compared
constraint-induced movement therapy with other intervention therapy. Overall,
constraint-induced movement therapy provided a medium beneficial effect (d =
0.546; p < 0.001) when compared with conventional therapy. For the subgroup
analyses, presence of a dose-equivalent comparison group, intervention location,
and time of follow-up were significant factors. Studies examining constraint
induced movement therapy effect without a dose-equivalent comparison group showed
a large effect in children with cerebral palsy, but studies with a dose
equivalent group only showed a small effect. Children who received home-based
constraint-induced movement therapy had a better improvement in arm function than
those who received constraint-induced movement therapy elsewhere. CONCLUSION: The
research literature supports constraint-induced movement therapy as an effective
intervention to improve arm function in children with cerebral palsy.
PMID- 25125441
TI - Efficacy of electrical stimulation as an adjunct to repetitive task practice
therapy on skilled hand performance in hemiparetic stroke patients: a randomized
controlled trial.
AB - OBJECTIVE: To assess the effects of additional electrical stimulation to hand
muscles combined with repetitive task practice therapy on skilled hand
performance in stroke patients. DESIGN: A randomized controlled study. SETTING:
Neurological physical therapy outpatient clinic. SUBJECTS: Forty stroke patients
of both sexes (45-65 years - 16 females and 24 males). METHODS: Participants were
randomly assigned into two equal groups: experimental and control groups. All
patients received repetitive task practice. Those in the experimental group
received additional electrical stimulation for specific hand muscles and patients
in the control group received sham electrical stimulation. Treatment was provided
three times/week for two months. MAIN OUTCOME MEASURES: Patients received
baseline and post-treatment assessments using three-dimensional motion analysis
(to evaluate range of motion of fingers abduction and extension), motor
assessment scale (to assess hand motor function) and time to complete Jebsen
Taylor Test (to assess hand skills). RESULTS: Patients in the experimental group
showed a significant improvement as compared with those in the control group.
Motor assessment scale score was 4.25+/-0.63 for the experimental group and
3.35+/-0.74 for the control group (t=-3.50 and p= 0.0001). Time to complete
Jebsen Taylor Test was 180.90+/-7.04 for the experimental group and 192.80+/-6.87
for the control group (t=4.50 and p= 0.0001). There was a significant improvement
in fingers abduction and extension in both groups (in favor to the experimental
group). CONCLUSION: Repetitive task practice therapy combined with electrical
stimulation can improve skilled hand performance in terms of hand motor function,
skills and range of motion in stroke patients.
PMID- 25125442
TI - Participant and caregiver experience of the Nintendo Wii SportsTM after stroke:
qualitative study of the trial of WiiTM in stroke (TWIST).
AB - OBJECTIVE: To understand stroke survivors and their caregivers' experience and
acceptability of using the Nintendo Wii SportsTM games (WiiTM) as a home-based
arm rehabilitation tool. DESIGN: A qualitative study within a randomized
controlled trial investigating the effectiveness of using the WiiTM for arm
rehabilitation. Data were analysed using thematic analysis. SETTINGS:
Participants and carers were interviewed in their homes. SUBJECTS: Eleven male
and seven female participants and 10 caregivers who were taking part in the
randomized controlled trial within six months of stroke. Median age 65.
INTERVENTION: All participants were using the WiiTM for arm rehabilitation. MAIN
MEASURES: Semi-structured interviews. RESULTS: Five themes were identified:
diligence of play, perceived effectiveness, acceptability, caregiver and social
support, and the set-up and administration of the WiiTM. Participants appreciated
the ability to maintain a social role and manage other comorbidities around the
use of the WiiTM. A small number of participants found the Mii characters too
childlike for adult rehabilitation. The most popular game to start the
rehabilitation programme was bowling. As confidence grew, tennis was the most
popular, with baseball and boxing being the least popular games. Caregivers
provided some practical support and encouragement to play the WiiTM. CONCLUSIONS:
The WiiTM may provide an engaging and flexible form of rehabilitation with
relatively high reported usage rates in a home setting. The WiiTM was acceptable
to this sample of patients and their caregivers in home-based rehabilitation of
the arm following stroke.
PMID- 25125444
TI - LeishMicrosatDB: open source database of repeat sequences detected in six fully
sequenced Leishmania genomes.
AB - A Leishmania Microsatellite Database (LeishMicrosatDB) is reported for genome
wise mining of microsatellites in six Leishmania species, using in silico
techniques. This was created to provide parasitologists a platform to understand
the genome characterization, mapping, phylogeny and evolutionary analysis. The
present version of the database contains 1,738,669 simple sequence repeats of
which 181 s756 repeats are present in compound form. The repeats can be sought in
a chromosome using input parameters such as repeat type (mono- hexa), coding
status, repeat unit length and repeat sequence motif. The genic repeats have been
further hyperlinked with their corresponding locus id, and the database is
appended with primer3 plus for primer designing of selected repeats with left and
right flanking sequences up to 250 bp. Information on clustering and polymorphic
repeats can also be retrieved. This database may also be adopted as a tool to
study the relative occurrence and distribution of microsatellites across the
parasitic genome. The database can enable a biologist to select markers at
desired intervals over the chromosomes, and can be accessed as an open source
repository at http://biomedinformri.com/leishmicrosat. DATABASE URL:
http://biomedinformri.com/leishmicrosat.
PMID- 25125443
TI - Mechanically-compliant intracortical implants reduce the neuroinflammatory
response.
AB - OBJECTIVE: The mechanisms underlying intracortical microelectrode encapsulation
and failure are not well understood. A leading hypothesis implicates the role of
the mechanical mismatch between rigid implant materials and the much softer brain
tissue. Previous work has established the benefits of compliant materials on
reducing early neuroinflammatory events. However, recent studies established late
onset of a disease-like neurodegenerative state. APPROACH: In this study, we
implanted mechanically-adaptive materials, which are initially rigid but become
compliant after implantation, to investigate the long-term chronic
neuroinflammatory response to compliant intracortical microelectrodes. MAIN
RESULTS: Three days after implantation, during the acute healing phase of the
response, the tissue response to the compliant implants was statistically similar
to that of chemically matched stiff implants with much higher rigidity. However,
at two, eight, and sixteen weeks post-implantation in the rat cortex, the
compliant implants demonstrated a significantly reduced neuroinflammatory
response when compared to stiff reference materials. Chronically implanted
compliant materials also exhibited a more stable blood-brain barrier than the
stiff reference materials. SIGNIFICANCE: Overall, the data show strikingly that
mechanically-compliant intracortical implants can reduce the neuroinflammatory
response in comparison to stiffer systems.
PMID- 25125446
TI - A brain-computer interface based on self-regulation of gamma-oscillations in the
superior parietal cortex.
AB - OBJECTIVE: Brain-computer interface (BCI) systems are often based on motor-
and/or sensory processes that are known to be impaired in late stages of
amyotrophic lateral sclerosis (ALS). We propose a novel BCI designed for patients
in late stages of ALS that only requires high-level cognitive processes to
transmit information from the user to the BCI. APPROACH: We trained subjects via
EEG-based neurofeedback to self-regulate the amplitude of gamma-oscillations in
the superior parietal cortex (SPC). We argue that parietal gamma-oscillations are
likely to be associated with high-level attentional processes, thereby providing
a communication channel that does not rely on the integrity of sensory- and/or
motor-pathways impaired in late stages of ALS. MAIN RESULTS: Healthy subjects
quickly learned to self-regulate gamma-power in the SPC by alternating between
states of focused attention and relaxed wakefulness, resulting in an average
decoding accuracy of 70.2%. One locked-in ALS patient (ALS-FRS-R score of zero)
achieved an average decoding accuracy significantly above chance-level though
insufficient for communication (55.8%). SIGNIFICANCE: Self-regulation of gamma
power in the SPC is a feasible paradigm for brain-computer interfacing and may be
preserved in late stages of ALS. This provides a novel approach to testing
whether completely locked-in ALS patients retain the capacity for goal-directed
thinking.
PMID- 25125445
TI - PlantCAZyme: a database for plant carbohydrate-active enzymes.
AB - PlantCAZyme is a database built upon dbCAN (database for automated carbohydrate
active enzyme annotation), aiming to provide pre-computed sequence and annotation
data of carbohydrate active enzymes (CAZymes) to plant carbohydrate and bioenergy
research communities. The current version contains data of 43,790 CAZymes of 159
protein families from 35 plants (including angiosperms, gymnosperms, lycophyte
and bryophyte mosses) and chlorophyte algae with fully sequenced genomes. Useful
features of the database include: (i) a BLAST server and a HMMER server that
allow users to search against our pre-computed sequence data for annotation
purpose, (ii) a download page to allow batch downloading data of a specific
CAZyme family or species and (iii) protein browse pages to provide an easy access
to the most comprehensive sequence and annotation data. DATABASE URL:
http://cys.bios.niu.edu/plantcazyme/
PMID- 25125447
TI - Clinical research: the future of the molecular imaging technologist-a white paper
presented by members of the graduate stakeholders committee of the SNMMI
technologist section.
PMID- 25125448
TI - Detection of Aberrant Right Subclavian Artery by PET/CT.
AB - An aberrant right subclavian artery can be diagnosed by PET/CT, as demonstrated
in this case of a 70-y-old man undergoing PET/CT for staging of squamous cell
carcinoma of the right lung. It is important to report this finding during the
evaluation of oncologic patients, to prevent severe complications that may arise
from various oncologic interventions.
PMID- 25125449
TI - Remote-controlled automatic injection versus manual injection in ictal SPECT of
seizure patients: experience from a children's hospital.
PMID- 25125450
TI - Bisphosphonate-associated atypical subtrochanteric femur fracture.
AB - Bisphosphonates help prevent progressive bone mineralization loss and subsequent
osteoporotic fractures. However, long-term bisphosphonate therapy paradoxically
increases the risk of a unique injury called an atypical subtrochanteric femur
fracture. Despite this, the benefits of bisphosphonates outweigh the risks,
because far more pathologic fractures are prevented than induced. The early
identification of atypical subtrochanteric femur fractures is important as there
is high associated morbidity and mortality. We describe a case of a 76-y-old
woman with a completed bisphosphonate-associated atypical subtrochanteric femur
fracture.
PMID- 25125451
TI - Examining the nuclear medicine advanced associate: past, present, and future-a
white paper presented by members of the graduate stakeholders committee of the
SNMMI technologist section.
PMID- 25125452
TI - Frailty modeling for clustered competing risks data with missing cause of
failure.
AB - Competing risks data often occur within a center in multi-center clinical trials
where the event times within a center may be correlated due to unobserved factors
across individuals. In this paper, we consider the cause-specific proportional
hazards model with a shared frailty to model the association between the event
times within a center in the framework of competing risks. We use a hierarchical
likelihood approach, which does not require any intractable integration over the
frailty terms. In a clinical trial, cause of death information may not be
observed for some patients. In such a case, analyses through exclusion of cases
with missing cause of death may lead to biased inferences. We propose a
hierarchical likelihood approach for fitting the cause-specific proportional
hazards model with a shared frailty in the presence of missing cause of failure.
We use multiple imputation methods to address missing cause of death information
under the assumption of missing at random. Simulation studies show that the
proposed procedures perform well, even if the imputation model is misspecified.
The proposed methods are illustrated with data from EORTC trial 30791 conducted
by European Organization for Research and Treatment of Cancer (EORTC).
PMID- 25125453
TI - Sample size determinations for group-based randomized clinical trials with
different levels of data hierarchy between experimental and control arms.
AB - We derived sample size formulae for detecting main effects in group-based
randomized clinical trials with different levels of data hierarchy between
experimental and control arms. Such designs are necessary when experimental
interventions need to be administered to groups of subjects whereas control
conditions need to be administered to individual subjects. This type of trial,
often referred to as a partially nested or partially clustered design, has been
implemented for management of chronic diseases such as diabetes and is beginning
to emerge more commonly in wider clinical settings. Depending on the research
setting, the level of hierarchy of data structure for the experimental arm can be
three or two, whereas that for the control arm is two or one. Such different
levels of data hierarchy assume correlation structures of outcomes that are
different between arms, regardless of whether research settings require two or
three level data structure for the experimental arm. Therefore, the different
correlations should be taken into account for statistical modeling and for sample
size determinations. To this end, we considered mixed-effects linear models with
different correlation structures between experimental and control arms to
theoretically derive and empirically validate the sample size formulae with
simulation studies.
PMID- 25125455
TI - Comprehensive data on ionising radiation from Fukushima Daiichi nuclear power
plant in the town of Miharu, Fukushima Prefecture: The Misho Project.
AB - Data related to radioactivity released from the Fukushima Daiichi Nuclear Power
Plant (FDNPP) accident on 15 March 2011 gathered by residents of Miharu,
Fukushima Prefecture, and by Tohoku University are presented. These data sets
consist of (1) the earliest radiation monitoring by a Geiger counter in the town,
(2) ratios of radioactivity between (132)Te and (137)Cs for a wide area between
Fukushima and Tokyo, (3) radiation measurement of soil samples collected from 18
school grounds, and (4) external radiation exposure of 1400 students using OSL
badges. By combining and analysing these various data sets, a curve for the
cumulative total external exposure as a function of time, with 16 : 00 h on 15
March 2011 being time zero, is obtained. The average cumulative external dosage
is estimated to be 10 mSv (sigma = 4.2 mSv) over 10 years. In addition, the
initiative that the residents of Miharu took in response to the FDNPP accident,
which became known as The Misho Project (MP), is documented; in particular, the
time at which the municipality instructed the immediate ingestion of iodine
tablets by those under the age of 40, 13 : 00 h on 15 March 2011, is assessed.
PMID- 25125454
TI - Continuous glucose monitoring in insulin-treated patients in non-ICU settings.
AB - Inpatient hyperglycemia, in patients with and without a history of diabetes, is
associated with increased risk of complications, mortality, and longer hospital
stay in medicine and surgical patients. Bedside capillary point of care testing
is widely recommended as the preferred method for glucose monitoring and for
guiding glycemic management of individual patients; however, the accuracy of most
handheld glucose meters is far from optimal. Recent studies in the hospital
setting have reported that the use of continuous glucose monitoring (CGM) can
provide real-time information about glucose concentration, direction, and rate of
change over a period of several days. Because it provides glucose values every 5
10 minutes 24 hours a day, CGM may have an advantage over point of care testing
with respect to reducing the incidence of severe hypoglycemia in acute care. Real
time CGM technology may facilitate glycemic control and to reduce hypoglycemia in
insulin-treated patients. Recent guidelines, however, have recommended deferring
the use of CGM in the adult hospital setting until further data on accuracy and
safety become available. In this study, we review the advantages and
disadvantages of the use of real-time CGM in the management of dysglycemia in the
hospital setting.
PMID- 25125456
TI - Foundations for literacy: An early literacy intervention for deaf and hard-of
hearing children.
AB - The present study evaluated the efficacy of a new preschool early literacy
intervention created specifically for deaf and hard-of-hearing (DHH) children
with functional hearing. Teachers implemented Foundations for Literacy with 25
DHH children in 2 schools (intervention group). One school used only spoken
language, and the other used sign with and without spoken language. A "business
as usual" comparison group included 33 DHH children who were matched on key
characteristics with the intervention children but attended schools that did not
implement Foundations for Literacy. Children's hearing losses ranged from
moderate to profound. Approximately half of the children had cochlear implants.
All children had sufficient speech perception skills to identify referents of
spoken words from closed sets of items. Teachers taught small groups of
intervention children an hour a day, 4 days a week for the school year. From fall
to spring, intervention children made significantly greater gains on tests of
phonological awareness, letter-sound knowledge, and expressive vocabulary than
did comparison children. In addition, intervention children showed significant
increases in standard scores (based on hearing norms) on phonological awareness
and vocabulary tests. This quasi-experimental study suggests that the
intervention shows promise for improving early literacy skills of DHH children
with functional hearing.
PMID- 25125457
TI - Cognitive and functional decline and their relationship in patients with mild
Alzheimer's dementia.
AB - BACKGROUND: In patients with Alzheimer's disease (AD), the relationship between
cognitive and functional progression is not fully understood; however, functional
decline has been postulated to follow cognitive decline. OBJECTIVE: To assess the
relationship between cognitive and functional treatment effects in mild AD
dementia patients. METHODS: Data of patients with mild AD were pooled from two
multicenter, double-blind, Phase 3 studies. Patients were randomized to infusions
of 400-mg solanezumab (n = 654), or placebo (n = 660) every 4 weeks for 18
months. Cognitive and functional outcome measures were assessed using the AD
Assessment Scale-Cognitive subscale (ADAS-Cog) and the AD Cooperative Study
Activities of Daily Living (ADCS-ADL), respectively. Analyses included
comparisons among normalized scales, correlations between outcome measures, and
path analyses to model the relationship of treatment effect on cognition and
function. RESULTS: Normalized ADAS-Cog and ADCS-ADL scales showed cognitive
impairment was more evident than functional impairment in mild AD. The
correlation between cognition and function increased over time. Path analyses
demonstrated that 87% of the treatment effect on function was driven by the
treatment effect on cognition, with the remaining 13% due to direct treatment
effect. CONCLUSION: Findings from this study are consistent with the hypothesis
that functional impairment is primarily driven by and follows cognitive decline
in mild AD dementia. The cognitive treatment effect appeared to explain the
majority of the functional treatment effect. It is possible that a cognitive
treatment effect may be considered as a leading indicator for functional outcomes
in an 18-month clinical trial for milder stages of AD.
PMID- 25125459
TI - Is brain copper deficiency in Alzheimer's, Lewy body, and Creutzfeldt Jakob
diseases the common key for a free radical mechanism and oxidative stress-induced
damage?
AB - In Alzheimer's (AD), Lewy body (LBD), and Creutzfeldt Jakob (CJD) diseases,
similar pathological hallmarks have been described, one of which is brain
deposition of abnormal protease-resistant proteins. For these pathologies, copper
bound to proteins is able to protect against free radicals by reduction from
cupric Cu++ to cupreous Cu+. We have previously demonstrated in bovine brain
homogenate that free radicals produce proteinase K-resistant prion after
manganese is substituted for copper. Since low brain copper levels have been
described in transmissible spongiform encephalopathies, in substantia nigra in
Parkinson's disease, and in various brain regions in AD, LBD, and CJD, a
mechanism has been proposed that may underlie the neurodegenerative processes
that occur when copper protection against free radicals is impaired. In peptide
sequences, the alpha acid proton near the peptide bond is highly mobile and can
be pulled out by free radicals. It will produce a trivalent alpha-carbon radical
and induce a free radical chain process that will generate a D-amino acid
configuration in the peptide sequence. Since only L-amino acids are
physiologically present in mammalian (human) proteins, it may be supposed that
only physiological L-peptides can be recycled by physiological enzymes such as
proteases. If a D-amino acid is found in the peptide sequence subsequent to
deficient copper protection against free radicals, it will not be recognized and
might alter the proteasome L-amino acid recycling from brain peptides. In the
brain, there will result an accumulation of abnormal protease-resistant proteins
such as those observed in AD, LBD, and CJD.
PMID- 25125460
TI - Awareness of disease is different for cognitive and functional aspects in mild
Alzheimer's disease: a one-year observation study.
AB - Awareness of disease can be compromised to some degree in a proportion of people
with dementia, with evident differences across domains. We designed this study to
determine the factors associated with the impairment of awareness over a period
of time. Using a longitudinal design, 69 people with mild Alzheimer's disease and
their family caregivers completed the Assessment Scale of Psychosocial Impact of
the Diagnosis of Dementia, the Quality of Life in Alzheimer's Disease Scale, the
Mini-Mental State Examination, the Clinical Dementia Rating Scale, the Cornell
Scale for Depression in Dementia, the Pfeffer Functional Activities
Questionnaire, the Neuropsychiatric Inventory, and the Zarit Burden Interview.
Univariate and logistic regression analyses were conducted to examine the
contribution of the various factors. The level of awareness of disease was
significantly lower (p <= 0.001) between baseline and at follow up. At follow up,
there was no change in the level of awareness of disease in 61.8%, whereas 25.4%
worsened. However, the level of awareness improved in 12.3%. Logistic regression
demonstrated that functional deficits (OR = 1.12, 95% CI: (1.03-1.22), p <=
0.01), and caregivers' quality of life (OR = 0.83, 95% CI: (0.70-0.98), p <=
0.05) were a significant predictor of impaired awareness of disease. The results
confirmed that awareness and cognition are relatively independent, and showed
that in people with mild dementia, unawareness is mainly manifested by poor
recognition of changes in the activities of daily living, and decrease in quality
of life.
PMID- 25125458
TI - Global N-acetylaspartate in normal subjects, mild cognitive impairment and
Alzheimer's disease patients.
AB - BACKGROUND: Mild cognitive impairment (MCI) is an intermediary state on the way
to Alzheimer's disease (AD). Little is known about whole brain concentration of
the neuronal marker, N-acetylaspartate (NAA) in MCI patients. OBJECTIVE: To test
the hypothesis that since MCI and AD are both neurodegenerative, quantification
of the NAA in their whole brain (WBNAA) could differentiate them from cognitively
intact matched controls. METHODS: Proton MR spectroscopy to quantify the WBNAA
was applied to 197 subjects (86 females) 72.6 +/- 8.4 years old (mean +/-
standard deviation). Of these, 102 were cognitively intact, 42 diagnosed as MCI,
and 53 as probable AD. Their WBNAA amounts were converted into absolute
concentration by dividing with the brain volume segmented from the MRI that also
yielded the fractional brain volume (fBPV), an atrophy metric. RESULTS: WBNAA
concentration of MCI and AD patients (10.5 +/- 3.0 and 10.1 +/- 2.9 mM) were not
significantly different (p = 0.85). They were, however, highly significantly 25
29% lower than the 14.1 +/- 2.4 mM of normal matched controls (p < 10-4). The
fBPV of MCI and AD patients (72.9 +/- 4.9 and 69.9 +/- 4.7%) differed
significantly from each other (4%, p = 0.02) and both were significantly lower
than the 74.6 +/- 4.4% of normal elderly (2%, p = 0.003 for MCI; 6%, p < 10-4 for
AD). ROC curve analysis has shown WBNAA to have 70.5% sensitivity and 84.3%
specificity to differentiate MCI or AD patients from normal elderly versus just
68.4 and 65.7% for fBPV. CONCLUSION: Low WBNAA in MCI patients compared with
cognitively normal contemporaries may indicate early neuronal damage accumulation
and supports the notion of MCI as an early stage of AD. It also suggests WBNAA as
a potential marker of early AD pathology.
PMID- 25125461
TI - Differences between mild cognitive impairment subtypes as indicated by event
related potential correlates of cognitive and motor processes in a Simon task.
AB - Mild cognitive impairment (MCI) may represent a prodromal stage of Alzheimer's
disease (AD), although the clinical manifestations of MCI are heterogeneous.
Consequently, MCI subtypes are differentiated since amnestic decline
(particularly when combined with decline on multiple cognitive domains) increases
the probability of progression to AD. In the present study, event-related
potential (ERP) correlates of stimulus evaluation (N2), visuospatial attention
(negativity posterior-contralateral, N2pc), stimulus categorization (P3b),
executive control (pre-response positivity, PP, and medial frontal negativity),
and motor (lateralized readiness potential, LRP) processes were studied in 53
participants while they performed a Simon task. Participants were divided into
control group (CG), multiple-domain non-amnestic MCI (mdnaMCI), single-domain
amnestic MCI (sdaMCI), and multiple-domain amnesic MCI (mdaMCI). Although there
were no differences in reaction times and percentage of errors in the performed
Simon-type task, a differential pattern of electrophysiological correlates was
observed in MCI compared to CG. Concretely, amnestic MCI (sdaMCI and mdaMCI)
showed reduced motor activity (LRP amplitude; AUC: 0.84); impairment in executive
control (PP amplitude; AUC: 0.80) was observed in multiple-domain MCI (mdaMCI and
mdnaMCI); finally, stimulus evaluation (N2 latency; AUC: 0.86) and visuospatial
attention (N2pc amplitude; AUC: 0.78) was affected in mdaMCI. Overall, results
linked the poorer prognosis of the mdaMCI subtype with a greater number of
differences in ERP correlates regarding CG. Therefore, the present results enable
us to suggest possible ERP biomarkers for specific MCI subtypes.
PMID- 25125462
TI - Closing-in is related to apathy in Alzheimer's disease patients.
AB - BACKGROUND: Apathy and depression are behavioral manifestations that may occur
often in Alzheimer's disease (AD) patients. AD patients may also show Closing-in
(CI) phenomenon, in graphic copying tasks. Recent evidence would suggest that
apathetic symptoms are related to frontal dysfunctions in AD patients, whereas
the cognitive bases of depressive symptoms in AD are still unclear. Recent
studies demonstrated that frontal dysfunctions are also involved in the genesis
of CI in AD patients. OBJECTIVE: Since frontal dysfunctions are thought to be
more strongly related to apathetic than depressive symptoms, here we tested the
hypothesis that CI is significantly associated with apathy in AD patients.
METHODS: Forty-four AD patients were enrolled for this study. All patients
completed a neuropsychological evaluation of visuo-spatial, frontal/executive,
visuo-constructional, and memory skills. Moreover, graphic copying tasks were
employed to detect CI, and behavioral scales to assess apathetic and depressive
symptoms. RESULTS: CI and apathetic and depressed symptoms occurred in more than
half of the present AD sample, but regression models revealed that the number of
CI was significantly related to apathy only. The number of CI was also
significantly correlated with severity of apathetic but not of depressive
symptoms. CONCLUSION: The present study demonstrated that CI and apathy are
correlated with each other in mild to moderate AD, likely because they share
common pathogenic mechanisms related to frontal/executive dysfunctions.
PMID- 25125463
TI - Cerebrospinal fluid alpha-synuclein and Lewy body-like symptoms in normal
controls, mild cognitive impairment, and Alzheimer's disease.
AB - BACKGROUND: Reduced cerebrospinal fluid (CSF) alpha-synuclein has been described
in synucleinopathies, including dementia with Lewy bodies (DLB). Common symptoms
of DLB include visual hallucinations and visuospatial and executive deficits. Co
occurrence of Lewy body pathology is common in Alzheimer's disease (AD) patients,
but it is unknown if reduced CSF alpha-synuclein is associated with Lewy body
like symptomatology in AD. OBJECTIVE: Determine associations between CSF alpha
synuclein and Lewy body-like symptomatology. METHODS: We included 73 controls
(NC), 121 mild cognitive impairment (MCI) patients, and 61 AD patients (median
follow-up 3.5 years, range 0.6-7.8). We tested associations between baseline CSF
alpha-synuclein and visual hallucinations and (longitudinal) cognition. Models
were tested with and without co-varying for CSF total tau (T-tau), which is
elevated in AD patients, and believed to reflect neurodegeneration. RESULTS:
Hallucinations were reported in 20% of AD patients, 13% of MCI patients, and 8%
of NC. In AD, low CSF alpha-synuclein was associated with hallucinations. When
adjusting for CSF T-tau, low CSF alpha-synuclein was associated with accelerated
decline of executive function (NC, MCI, and AD), memory (MCI and AD), and
language (MCI). CONCLUSION: The associations of low CSF alpha-synuclein with
hallucinations and poor executive function, which are hallmarks of DLB,
indirectly suggest that this biomarker may reflect underlying synuclein
pathology. The associations with memory and language in MCI and AD suggests
either that reduced CSF alpha-synuclein also partly reflects global impaired
neuronal/synaptic function, or that non-specific overall cognitive deterioration
is accelerated in the presence of synuclein related pathology. The findings will
require autopsy verification.
PMID- 25125465
TI - ABCA5 regulates amyloid-beta peptide production and is associated with
Alzheimer's disease neuropathology.
AB - Brain cholesterol homeostasis is regulated by a group of proteins called ATP
binding cassette subfamily A (ABCA) transporters. Certain ABCA transporters
regulate amyloid-beta protein precursor (AbetaPP) processing to generate amyloid
beta peptides (Abeta) and are associated with an increased risk for late-onset
Alzheimer's disease (AD). ABCA5 is a little-known member of the ABCA subfamily
with no known function. In this study we undertook a comprehensive analysis of
ABCA5 expression in the human and mouse brains. We explored the potential role of
ABCA5 in AbetaPP processing associated with AD pathology. ABCA5 was
differentially expressed in multiple regions of both human and mouse brains. It
was strongly expressed in neurons with only weak expression in microglia,
astrocytes, and oligodendrocytes. ABCA5 was able to stimulate cholesterol efflux
in neurons. ABCA5 expression was specifically elevated in the hippocampus of AD
brains. Using two in vitro cell systems we demonstrated that ABCA5 reduces Abeta
production, both Abeta40 and Abeta42, without altering AbetaPP mRNA and protein
levels, indicating that the decrease in the Abeta levels was due to changes in
AbetaPP processing and not AbetaPP expression. This report represents the first
extensive expression and functional study of ABCA5 in the human brain and our
data suggest a plausible function of ABCA5 in the brain as a cholesterol
transporter associated with Abeta generation, information that may offer a
potential new target for controlling Abeta levels in the brain.
PMID- 25125466
TI - Cerebrospinal fluid apolipoprotein E concentration and progression of Alzheimer's
disease.
AB - BACKGROUND/OBJECTIVE: Apolipoprotein E plays a role in the pathogenesis of
Alzheimer's disease (AD). Cerebrospinal fluid (CSF) and plasma level alterations
have been reported in AD patients. In search of a potential biomarker, which
would be predictive of cognitive, functional, or motor decline, we analyzed CSF
apolipoprotein E (ApoE) levels of AD patients in this regard. METHODS: Subjects
with newly diagnosed AD enrolled into an observational study were followed up
longitudinally. Neuropsychological testing and physical examination were
performed annually. In a sub-cohort of patients, where baseline CSF ApoE
concentration values were available, multiple regression analyses were used to
determine possible associations of CSF ApoE concentration and speed of decline on
different cognitive, functional, and motor scales (MMSE, iADL, bADL, GDS,
UPDRSIII) adjusting for possible confounders. RESULTS: No association of CSF ApoE
levels and speed of decline on the various scales could be established (p = 0.09
to 0.88). Nevertheless, the use of neuroleptic drugs could be linked to higher
velocity of global and extrapyramidal deterioration (p = 0.04 and 0.05 for GDS
and UPDRSIII, respectively), but not to other outcomes (MMSE, bADL, and iADL).
CONCLUSION: Herein, CSF ApoE at time of AD diagnosis could not be shown to be a
viable biomarker for future cognitive, functional, or motor decline. Expectedly,
the use of neuroleptic drugs was associated with detrimental effects.
PMID- 25125464
TI - Increased tau phosphorylation and aggregation in the hippocampus of mice
overexpressing corticotropin-releasing factor.
AB - Clinical and basic science research suggests that stress and/or changes in
central stress signaling intermediates may be involved in Alzheimer's disease
(AD) pathogenesis. Although the links between stress and AD remain unsettled,
data from our group and others have established that stress exposure in rodents
may confer susceptibility to AD pathology by inducing hippocampal tau
phosphorylation (tau-P). Work in our laboratory has shown that stress-induced tau
P requires activation of the type-1 corticotropin-releasing factor receptor
(CRFR1). CRF overexpressing (CRF-OE) mice are a model of chronic stress that
display cognitive impairment at 9-10 month of age. In this study we used 6-7
month old CRF-OE mice to examine whether sustained exposure to CRF and stress
steroids would impact hippocampal tau-P and kinase activity in the presence or
absence of the CRFR1-specific antagonist, R121919, given daily for 30 days. CRF
OE mice had significantly elevated tau-P compared to wild type (WT) mice at the
AT8 (S202/T204), PHF-1 (S396/404), S262, and S422 sites. Treating CRF-OE mice
with R121919 blocked phosphorylation at the AT8 (S202/T204) and PHF-1 (S396/404)
sites, but not at the S262 and S422 sites and reduced phosphorylation of c-Jun N
Terminal Kinase (JNK). Examination of hippocampal extracts from CRF-OE mice at
the ultrastructural level revealed negatively stained round/globular aggregates
that were positively labeled by PHF-1. These data suggest critical roles for CRF
and CRFR1 in tau-P and aggregation and may have implications for the development
of AD cognitive decline.
PMID- 25125467
TI - Serum MHPG strongly predicts conversion to Alzheimer's disease in behaviorally
characterized subjects with Down syndrome.
AB - BACKGROUND: Down syndrome (DS) is the most prevalent genetic cause of
intellectual disability. Early-onset Alzheimer's disease (AD) frequently develops
in DS and is characterized by progressive memory loss and behavioral and
psychological signs and symptoms of dementia (BPSD). Predicting and monitoring
the progression of AD in DS is necessary to enable adaptive caretaking.
OBJECTIVE: Reliable blood biomarkers that aid the prediction of AD are necessary,
since cerebrospinal fluid sampling is rather burdensome, particularly for people
with DS. Here, we investigate serum levels of eight biogenic amines and their
metabolites in relation to dementia staging and probable BPSD items. METHODS:
Using RP-HPLC with electrochemical detection, (nor)adrenergic (NA/A and MHPG),
serotonergic (5-HT and 5-HIAA), and dopaminergic (DA, HVA, and DOPAC) compounds
were quantified in the serum of DS subjects with established AD at baseline (n =
51), DS subjects without AD (n = 50), non-demented DS individuals that converted
to AD over time (n = 50), and, finally, healthy non-DS controls (n = 22).
RESULTS: Serum MHPG levels were significantly lower in demented and converted DS
subjects (p < 0.0001) compared to non-demented DS individuals and healthy
controls. Those subjects with MHPG levels below median had a more than tenfold
increased risk of developing dementia. Furthermore, significant correlations were
observed between monoaminergic serum values and various probable BPSD items
within each DS group. CONCLUSION: Decreased serum MHPG levels show great
potential as biomarker to monitor and predict conversion to AD in DS. Moreover,
significant monoaminergic alterations related to probable BPSD items, suggesting
that monoaminergic dysregulation is an underlying biological mechanism, and
demonstrating the need to develop a validated rating scale for BPSD in DS.
PMID- 25125469
TI - The microbiome and disease: reviewing the links between the oral microbiome,
aging, and Alzheimer's disease.
AB - This review, gathered from diverse sources, shows how our microbiome influences
health and ultimately how well we age. Evidence linking oral bacteria to
Alzheimer's disease (AD) is discussed in the context of aging, drawing together
data from epidemiological, experimental, genetic, and environmental studies.
Immunosenescence results in increased bacterial load as cell-mediated and humoral
immune responses wane. The innate immune system gradually takes over;
contributing to the rise in circulating proinflammatory cytokines such as
TNFalpha. Maintaining the integrity of the blood-brain barrier (BBB) against a
backdrop of increasing bacterial load is important. Aging may favor the
proliferation of anaerobes in the mouth eliciting a robust TNFalpha response from
the oral epithelium. Prolonged exposure to high levels of circulating TNFalpha
compromises the integrity of the BBB. Sensitive techniques now detect the
"asymptomatic" presence of bacteria in areas previously thought to be sterile,
providing new insights into the wider distribution of components of the
microbiome. These "immune-tolerated" bacteria may slowly multiply elsewhere until
they elicit a chronic inflammatory response; some are now considered causal in
instances of atherosclerosis and back pain. Inflammatory processes have long been
associated with AD. We propose for a subset of AD patients, aging favors the
overgrowth of oral anaerobes established earlier in life provoking a pro
inflammatory innate response that weakens the BBB allowing bacteria to spread and
quietly influence the pathogenesis of AD. Finally, we suggest that human
polymorphisms considered alongside components of the microbiome may provide new
avenues of research for the prevention and treatment of disease.
PMID- 25125468
TI - Restoration of lipoxin A4 signaling reduces Alzheimer's disease-like pathology in
the 3xTg-AD mouse model.
AB - The initiation of an inflammatory response is critical to the survival of an
organism. However, when inflammation fails to reach resolution, a chronic
inflammatory state may occur, potentially leading to bystander tissue damage.
Accumulating evidence suggests that chronic inflammation contributes to the
progression of Alzheimer's disease (AD), and identifying mechanisms to resolve
the pro-inflammatory environment stimulated by AD pathology remains an area of
active investigation. Previously, we found that treatment with the pro-resolving
mediator aspirin-triggered lipoxin A4 (ATL), improved cognition, reduced Abeta
levels, and enhanced microglia phagocytic activity in Tg2576 transgenic AD mice.
Here, we evaluated the effect of aging on brain lipoxin A4 (LXA4) levels using
non-transgenic and 3xTg-AD mice. Additionally, we investigated the effect of ATL
treatment on tau pathology in 3xTg-AD mice. We found that LXA4 levels are reduced
with age, a pattern significantly more impacted in 3xTg-AD mice. Moreover, ATL
delivery enhanced the cognitive performance of 3xTg-AD mice and reduced Abeta
levels, as well as decreased the levels of phosphorylated-tau (p-tau). The
decrease in p-tau was due in part to an inhibition of the tau kinases GSK-3beta
and p38 MAPK. In addition, microglial and astrocyte reactivity was inhibited by
ATL treatment. Our results suggest that the inability to resolve the immune
response during aging might be an important feature that contributes to AD
pathology and cognitive deficits. Furthermore, we demonstrate that activation of
LXA4 signaling could serve as a potential therapeutic target for AD-related
inflammation and cognitive dysfunction.
PMID- 25125470
TI - Direct visualization of fungal infection in brains from patients with Alzheimer's
disease.
AB - Recently, we have reported the presence of fungal infections in patients with
Alzheimer's disease (AD). Accordingly, fungal proteins and DNA were found in
brain samples, demonstrating the existence of infection in the central nervous
system. In the present work, we raised antibodies to specific fungal species and
performed immunohistochemistry to directly visualize fungal components inside
neurons from AD patients. Mice infected with Candida glabrata were initially used
to assess whether yeast can be internalized in mammalian tissues. Using
polyclonal rabbit antibodies against C. glabrata, rounded immunopositive cells
could be detected in the cytoplasm of cells from liver, spleen, and brain samples
in infected, but not uninfected, mice. Immunohistochemical analyses of tissue
from the frontal cortex of AD patients revealed the presence of fungal material
in a small percentage (~10%) of cells, suggesting the presence of infection.
Importantly, this immunopositive material was absent in control samples. Confocal
microscopy indicated that this fungal material had an intracellular localization.
The specific morphology of this material varied between patients; in some
instances, disseminated material was localized to the cytoplasm, whereas small
punctate bodies were detected in other patients. Interestingly, fungal material
could be revealed using different anti-fungal antibodies, suggesting multiple
infections. In summary, fungal infection can only be observed using specific anti
fungal antibodies and only a small percentage of cells contain fungi. Our
findings provide an explanation for the hitherto elusive detection of fungi in AD
brains, and are consistent with the idea that fungal cells are internalized
inside neurons.
PMID- 25125471
TI - Medication cost of persons with dementia in primary care in Germany.
AB - BACKGROUND: Results of cost-of-illness studies in dementia have shown a
considerable divergence in costs of medication for persons with dementia.
However, detailed economic analyses of medication costs for community-dwelling
persons with dementia are currently still missing, especially on the basis of
primary data. OBJECTIVE: To determine medication cost, cost per drug, and number
of drugs taken of community-dwelling persons with dementia and analyze their
associated factors; to estimate the current price reduction of anti-dementia
drugs due to implementation of low-priced generics. METHOD: The present analysis
included 205 patients screened positive for dementia. Medication data were
assessed within a medication review. To estimate the cost effect of implementing
generics, the most favorable equivalent generic was assigned to each anti
dementia drug. Factors associated with medication cost, cost per drug, and number
of drugs taken were evaluated using multiple regression models. RESULTS:
Medication cost and cost per drug were higher and the number of taken drugs lower
in advanced stages of cognitive impairment. Prescription of anti-dementia
generics could decrease overall medication cost by 28%. Medication cost was
associated with number of diagnoses, deficits in activities of daily living, and
age. Dementia severity was related to cost per drug and number of drugs taken.
CONCLUSION: Medication cost increases with the number of diagnoses and growing
deficits in activities of daily living and decreases with age. Severely
cognitively impaired persons are treated with a small number of high-priced
drugs, which could suggest inadequate medication of multimorbid persons.
PMID- 25125472
TI - Rice bran extract compensates mitochondrial dysfunction in a cellular model of
early Alzheimer's disease.
AB - Mitochondrial dysfunction plays an important role in brain aging and has emerged
to be an early event in Alzheimer's disease (AD), contributing to
neurodegeneration and the loss of physical abilities seen in patients suffering
from this disease. We examined mitochondrial dysfunction in a cell culture model
of AD (PC12APPsw cells) releasing very low amyloid-beta (Abeta40) levels and thus
mimicking early AD stages. Our data show that these cells have impaired energy
metabolism, low ATP levels, and decreased endogenous mitochondrial respiration.
Furthermore, protein levels of PGC1alpha as well as of Mitofusin 1 were
decreased. PC12APPsw cells also showed increased mitochondrial content, probably
due to an attempt to compensate the impaired mitochondrial function. Recent data
showed that stabilized rice bran extract (RBE) protects from mitochondrial
dysfunction in vivo Pharmacol Res. (2013) 76C, 17-27. To assess the effect of RBE
on mitochondrial function, we treated PC12APPsw cells for 24 h with RBE. Key
components of RBE are oryzanols, tocopherols, and tocotrienols, all substances
that have been found to exert beneficial effects on mitochondrial function. RBE
incubation elevated ATP production and respiratory rates as well as PGC1alpha
protein levels in PC12APPsw cells, thus improving the impaired mitochondrial
function assessed in our cell culture AD model. Therefore, RBE represents to be a
promising nutraceutical for the prevention of AD.
PMID- 25125473
TI - Phosphodiesterase inhibition in cognitive decline.
AB - Understanding the cellular and molecular processes involved in learning and
memory will help in the development of safe and effective cognitive enhancers.
The cAMP response element-binding (CREB) may be a universal modulator of
processes required for memory formation, and increasing the levels of second
messengers like cAMP and cGMP could ultimately lead to CREB activation.
Phosphodiesterase (PDE) inhibitors regulate signaling pathways by elevating cAMP
and/or cGMP levels, and they have been demonstrated to improve learning and
memory in a number of rodent models of impaired cognition. The aim of this review
is to summarize the outstanding progress that has been made in the application of
PDE inhibitors for memory dysfunction. In addition, we have introduced some
recent data we generated demonstrating that tadalafil could be considered as an
optimal candidate for drug re-positioning and as a good candidate to enhance
cognition.
PMID- 25125474
TI - Enhanced neurite outgrowth and branching precede increased amyloid-beta-induced
neuronal apoptosis in a novel Alzheimer's disease model.
AB - Though it is widely accepted that amyloid-beta (Abeta) is a key factor in
Alzheimer's disease (AD) pathology, its underlying mechanism remains unclear. In
order to study the association between Abeta and neural circuitry dysfunction, we
developed a primary culture preparation derived from the nervous system of
transgenic Drosophila melanogaster larvae expressing human Abeta1-42 (Abeta42).
Cultured neurons undergo a consistent developmental process, culminating in an
elaborate neuronal network with distinct functional and morphological
characteristics. Throughout this development, a time-dependent increase in
intracellular expression levels of Abeta42 was detected, followed by
extracellular staining at a later time point. When compared to controls, Abeta42
cultures exhibited enhanced levels of apoptosis, resulting in reduced cell
viability. Moreover, as primary culture preparations enable high resolution
monitoring of neuronal phenotypes, we were able to detect subtle morphological
changes in neurons expressing Abeta42, namely an enhancement in neurite outgrowth
and arborization, which preceded the effect of neurodegeneration. Our results
establish D. melanogaster primary neuronal cultures as a rapid, accessible and
cost-effective platform for AD molecular studies and drug screening, and suggest
a possible role for Abeta42 in the organization of neuronal processes.
PMID- 25125475
TI - Cannabis-based medicine reduces multiple pathological processes in AbetaPP/PS1
mice.
AB - Several recent findings suggest that targeting the endogenous cannabinoid system
can be considered as a potential therapeutic approach to treat Alzheimer's
disease (AD). The present study supports this hypothesis demonstrating that delta
9-tetrahydrocannabinol (THC) or cannabidiol (CBD) botanical extracts, as well as
the combination of both natural cannabinoids, which are the components of an
already approved cannabis-based medicine, preserved memory in AbetaPP/PS1
transgenic mice when chronically administered during the early symptomatic stage.
Moreover, THC + CBD reduced learning impairment in AbetaPP/PS1 mice. A
significant decrease in soluble Abeta42 peptide levels and a change in plaques
composition were also observed in THC + CBD-treated AbetaPP/PS1 mice, suggesting
a cannabinoid-induced reduction in the harmful effect of the most toxic form of
the Abeta peptide. Among the mechanisms related with these positive cognitive
effects, the anti-inflammatory properties of cannabinoids may also play a
relevant role. Here we observed reduced astrogliosis, microgliosis, and
inflammatory-related molecules in treated AbetaPP/PS1 mice, which were more
marked after treatment with THC + CBD than with either THC or CBD. Moreover,
other cannabinoid-induced effects were uncovered by a genome-wide gene expression
study. Thus, we have identified the redox protein thioredoxin 2 and the signaling
protein Wnt16 as significant substrates for the THC + CBD-induced effects in our
AD model. In summary, the present findings show that the combination of THC and
CBD exhibits a better therapeutic profile than each cannabis component alone and
support the consideration of a cannabis-based medicine as potential therapy
against AD.
PMID- 25125476
TI - Impaired lysosomal cobalamin transport in Alzheimer's disease.
AB - Cobalamin (vitamin B12) is required for erythrocyte formation and DNA synthesis
and it plays a crucial role in maintaining neurological function. As a coenzyme
for methionine synthase and methylmalonyl-CoA mutase, cobalamin utilization
depends on its efficient transit through the intracellular lysosomal compartment
and subsequent delivery to the cytosol and mitochondria. Lysosomal function
deteriorates in Alzheimer's disease (AD). Lysosomal acidification is defective in
AD and lysosomal proteolysis is disrupted by AD-related presenilin 1 mutation. In
this study, we propose that AD related lysosomal dysfunction may impair lysosomal
cobalamin transport. The experiments use in vitro and in vivo models of AD to
define how lysosomal dysfunction directly affects cobalamin utilization. SH-SY5Y
AbetaPP mutant cells were treated with a proteasome inhibitor to induce lysosomal
amyloid-beta accumulation. We metabolically labeled these cells with [57Co]
cobalamin and isolated purified lysosomes, mitochondria, and cytosol fractions.
The results indicated that proteasome inhibition was associated with lysosomal
amyloid-beta accumulation and a doubling of lysosomal [57Co] cobalamin levels. We
also used AbetaPPxPS1 transgenic AD mice that were intraperitoneally injected
with [57Co] cobalamin. The amount of [57Co] cobalamin in the major organs of
these mice was measured and the subcellular [57Co] cobalamin distribution in the
brain was assessed. The results demonstrated that lysosomal [57Co] cobalamin
level was significantly increased by 56% in the AbetaPPxPS1 AD mouse brains as
compared to wild type control mice. Together these data provide evidence that
lysosomal cobalamin may be impaired in AD in association with amyloid-beta
accumulation.
PMID- 25125477
TI - PKCepsilon deficits in Alzheimer's disease brains and skin fibroblasts.
AB - In Alzheimer's disease (AD) transgenic mice, activation of synaptogenic protein
kinase C epsilon (PKCepsilon) was found to prevent synaptotoxic amyloid-beta
(Abeta)-oligomer elevation, PKCepsilon deficits, early synaptic loss, cognitive
deficits, and amyloid plaque formation. In humans, to study the role of
PKCepsilon in the pathophysiology of AD and to evaluate its possible use as an
early AD-biomarker, we examined PKCepsilon and Abeta in the brains of autopsy
confirmed AD patients (n = 20) and age-matched controls (AC, n = 19), and in skin
fibroblast samples from AD (n = 14), non-AD dementia patients (n = 14), and AC (n
= 22). Intraneuronal Abeta levels were measured immunohistochemically (using an
Abeta-specific antibody) in hippocampal pyramidal cells of human autopsy brains.
PKCepsilon was significantly lower in the hippocampus and temporal pole areas of
AD brains, whereas Abeta levels were significantly higher. The ratio of
PKCepsilon to Abeta in individual CA1 pyramidal cells was markedly lower in the
autopsy AD brains versus controls. PKCepsilon was inversely correlated with Abeta
levels in controls, whereas in AD patients, PKCepsilon showed no significant
correlation with Abeta. In autopsy brains, PKCepsilon decreased as the Braak
score increased. Skin fibroblast samples from AD patients also demonstrated a
deficit in PKCepsilon compared to controls and an AD-specific change in the Abeta
oligomer effects on PKCepsilon. Together, these data demonstrate that the
relationship between Abeta levels and PKCepsilon is markedly altered in AD
patients' brains and skin fibroblasts, reflecting a loss of protective effect of
PKCepsilon against toxic Abeta accumulation. These changes of PKCepsilon levels
in human skin fibroblasts may provide an accurate, non-invasive peripheral AD
biomarker.
PMID- 25125478
TI - The multiple lifestyle modification for patients with prehypertension and
hypertension patients: a systematic review protocol.
AB - INTRODUCTION: The objective of this systematic review is to investigate the
effectiveness, efficacy and safety of multiple concomitant lifestyle modification
therapies for patients with hypertension or prehypertension. METHODS AND
ANALYSIS: Electronic searches will be performed in the Cochrane Library, OVID,
EMBASE, etc, along with manual searches in the reference lists of relevant papers
found during electronic search. We will identify eligible randomised controlled
trials utilising multiple lifestyle modifications to lower blood pressure. The
control could be drug therapy, single lifestyle change or no intervention.
Changes in systolic blood pressure and diastolic blood pressure constitute
primary end points, and secondary end points include the number of patients
meeting the office target blood pressure, the number of patients reporting
microvascular or macrovascular complications, etc. We will extract descriptive,
methodological and efficacy data from identified randomised controlled trials
(RCTs). We will calculate the relative risk for proportion of patients with a
normal blood pressure in the experimental group. Dichotomous data will be
analysed using risk difference and continuous data using weighted mean
differences, both with 95% CI. We will use the chi(2) test and the I(2) statistic
to assess heterogeneity. We will use the fixed effects model to compute the
efficacy unless there is evidence of heterogeneity. If heterogeneity of effect
size persists with respect to blood pressure change, further metaregression will
be performed within groups. We will examine the potential for publication bias by
using a funnel plot. DISSEMINATION: We will synthesise results from RCTs which
provide more precise and accurate information on the effect of multiple lifestyle
changes on blood pressure. The results of this review will increase the
understanding of multiple lifestyle modifications for patients with hypertension
or prehypertension. TRAIL REGISTRATION NUMBER: Our protocol is registered on
PROSPERO (CRD42013006476), http://www.crd.your.ac.uk/PROSPERO.
PMID- 25125479
TI - Potential risk of TNF inhibitors on the progression of interstitial lung disease
in patients with rheumatoid arthritis.
AB - OBJECTIVES: Biological therapy represents important advances in alleviating
rheumatoid arthritis (RA), but the effect on interstitial lung disease (ILD) has
been controversial. The objective of this study was to assess the risk of such
treatment for patients with ILD. DESIGN: Case-control cohorts. SETTING: Single
centre in Japan. PARTICIPANTS: This study included 163 patients with RA who
underwent biological therapy. OUTCOME MEASURED: We assessed chest CT before
initiation of biological therapy and grouped 163 patients according to the
presence of ILD (with (n=58) and without pre-existing ILD (n=105)). Next, we
evaluated serial changes of chest CT after treatment and visually assessed the
emergence of ILD or its progression, which was referred to as an 'ILD event'.
Then, we also classified the patients according to the presence of ILD events and
analysed their characteristics. RESULTS: Tumour necrosis factor (TNF) inhibitors
were administered to more patients with ILD events than those without ILD events
(88% vs 60%, p<0.05), but recipients of tocilizumab or abatacept did not differ
in this respect. Of 58 patients with pre-existing ILD, 14 had ILD events, and
that proportion was greater than for those without pre-existing ILD (24% vs 3%,
p<0.001). Of these 14 patients, all were treated with TNF inhibitors. Four
patients developed generalised lung disease and two died from ILD progression.
Baseline levels of KL-6 were similar in both groups, but increased in patients
with ILD events. CONCLUSIONS: TNF inhibitors have the potential risk of ILD
events, particularly for patients with pre-existing ILD, and KL-6 is a valuable
surrogate marker for detecting ILD events. Our data suggest that non-TNF
inhibitors are a better treatment option for these patients.
PMID- 25125480
TI - Reduction in stillbirths at term after new birth induction paradigm: results of a
national intervention.
AB - OBJECTIVE: The risk of fetal death increases steeply after 42 gestational weeks.
Since 2009, Denmark has had a more proactive policy including prevention of
prolonged pregnancy, and early intervention in women with diabetes, preeclampsia,
high body mass index and of a higher age group. The aim of this study was to
describe the development in fetal deaths with this more proactive birth induction
practice, and to identify and quantify contributing factors for this development.
DESIGN: National cohort study. SETTING: Denmark. PARTICIPANTS: Delivering women
in Denmark, 1 January 2000 to 31 December 2012. OUTCOME MEASURES: Stillbirths per
1000 women at risk (prospective risk of stillbirth) and per 1000 newborn from 37
and 40 gestational weeks, respectively, through the study period. RESULTS: During
the study period, 829,165 children were live born and 3770 (0.45%) stillborn.
Induction of labour increased from 12.4% in year 2000 to 25.1% in 2012 (p<0.001),
and the percentage of children born at or after 42 weeks decreased from 8.0% to
1.5% (p<0.001). Through the same period, the prospective risk of stillbirth after
37 weeks fell from 0.70 to 0.41/1000 ongoing pregnancies (p<0.001), and from 2.4
to 1.4/1000 newborn (p<0.001). The regression analysis confirmed the inverse
association between year of birth and risk of stillbirth. The lowest risk was
observed in the years 2011-2012 as compared with years 2000-2002 with a fully
adjusted HR of 0.69 (95% CI 0.57 to 0.83). The general earlier induction, the
focused earlier induction of women with body mass index >30, twins, and of women
above 40 years and a halving of smoking pregnant women were all independent
contributing factors for the decrease. CONCLUSIONS: A gradually more proactive
and differential earlier labour induction practice is likely to have mainly been
responsible for the substantial reduction in stillbirths in Denmark.
PMID- 25125482
TI - Preclinical characterization of 5-amino-4-oxo-[6-11C]hexanoic acid as an imaging
probe to estimate protoporphyrin IX accumulation induced by exogenous
aminolevulinic acid.
AB - Preoperative noninvasive imaging to estimate the quantity and spatial
distribution of protoporphyrin IX (PpIX) accumulation in tumors induced by 5
aminolevulinic acid (ALA) administration is expected to improve the efficacy of
ALA-based fluorescence-guided resection and photo- and sonodynamic therapies.
PpIX synthesis from exogenous ALA has been reported to be regulated by ALA influx
or ALA dehydratase (ALAD) activity, which catalyzes the first step of the
synthesis. In this study, we characterized the properties of a (11)C-labeled ALA
analog, 5-amino-4-oxo-[6-(11)C]hexanoic acid ((11)C-MALA), as a PET tracer to
estimate PpIX accumulation. METHODS: In vitro uptake of (11)C-MALA and (3)H-ALA
was determined in 5 tumor cell lines after 10-min incubation with each tracer at
37 degrees C. The expression levels of ALAD were determined by Western blot
analysis. In vivo distribution and dynamic PET studies were conducted in tumor
bearing mice. In vitro and in vivo accumulation of ALA-induced PpIX was
determined by measuring fluorescence in extracts of cells or tumors. RESULTS: In
vitro uptake of (11)C-MALA in 5 tumor cell lines was correlated with ALAD
expression levels and PpIX accumulation. In vivo biodistribution and dynamic PET
studies showed that (11)C-MALA was rapidly incorporated into tumors, and the
tumor-to-muscle ratio of (11)C-MALA at 1 min after injection was significantly
correlated with that of (3)H-ALA. (11)C-MALA in tumors was continuously decreased
thereafter, and the elimination rate of (11)C-MALA from AsPC-1 tumors with the
highest ALAD expression level was slower than from other tumors with lower
expression levels. These results suggest that the influx and intracellular
retention of (11)C-MALA reflect ALA influx and ALAD expression levels,
respectively. Tumor accumulation of (11)C-MALA at 60 min after injection was
strongly correlated with PpIX accumulation in tumor tissues. CONCLUSION: (11)C
MALA PET has the potential to noninvasively estimate the quantitative and spatial
accumulation of exogenous ALA-induced PpIX.
PMID- 25125481
TI - Comparison of the amino acid tracers 18F-FET and 18F-DOPA in high-grade glioma
patients.
AB - High-grade gliomas (HGGs) are the most common malignant primary tumors of the
central nervous system. PET probes of amino acid transport such as O-(2-(18)F
fluoroethyl)-l-tyrosine ((18)F-FET), 3,4-dihydroxy-6-(18)F-fluoro-l-phenylalanine
((18)F-DOPA), and (11)C-methionine ((11)C-MET) detect primary and recurrent
tumors with a high accuracy. (18)F-FET is predominantly used in Europe, whereas
amino acid transport imaging is infrequently done in the United States. The aim
of this study was to determine whether (18)F-FET and (18)F-DOPA PET/CT provide
comparable information in HGG. METHODS: Thirty (18)F-FET and (18)F-DOPA PET/CT
scans were obtained before surgery or biopsy in 27 patients with high clinical
suspicion for primary or recurrent HGG (5 primary, 22 recurrent tumors). (18)F
FET and (18)F-DOPA PET/CT images were compared visually and semiquantitatively
(maximum standardized uptake value [SUV(max)], mean SUV [SUV(mean)]). Background
(SUV(max) and SUV(mean)) and tumor-to-background ratios (TBRs) were calculated
for both PET probes. The degree of (18)F-DOPA uptake in the basal ganglia
(SUV(mean)) was also assessed. RESULTS: Visual analysis revealed no difference in
tumor uptake pattern between the 2 PET probes. The SUV(mean) and SUV(max) for
(18)F-FET were higher than those of (18)F-DOPA (4.0 +/- 2.0 and 4.9 +/- 2.3 vs.
3.5 +/- 1.6 and 4.3 +/- 2.0, respectively; all P < 0.001). TBRs for SUV(mean) but
not for SUV(max) were significantly higher for (18)F-FET than (18)F-DOPA (TBR
SUV(mean): 3.8 +/- 1.7 vs. 3.4 +/- 1.2, P = 0.004; TBR SUV(max): 3.3 +/- 1.6 and
3.0 +/- 1.1, respectively; P = 0.086). (18)F-DOPA uptake by the basal ganglia was
present (SUV(mean), 2.6 +/- 0.7) but did not affect tumor visualization.
CONCLUSION: Whereas visual analysis revealed no significant differences in uptake
pattern for (18)F-FET and (18)F-DOPA in patients with primary or recurrent HGG,
both SUVs and TBRs for SUV(mean) were significantly higher for (18)F-FET.
However, regarding tumor delineation, both tracers performed equally well and
seem equally feasible for imaging of primary and recurrent HGG. These findings
suggest that both PET probes can be used based on availability in multicenter
trials.
PMID- 25125483
TI - Iatrogenic parkinsonism: the role of flunarizine and cinnarizine.
AB - We performed a clinical report based, descriptive and retrospective study, aimed
at comparing Flunarizine/Cinnarizine-induced parkinsonism (FCIP) patients and
Parkinson's disease (PD) patients. The FCIP group (n = 30) presented a lower
frequency of rigidity and unilateral tremor than the PD group (n = 70). All FCIP
patients improved, 13 after dopaminergic treatment. FCIP patients who improved
spontaneously presented lower frequency of rigidity, compared with the other FCIP
subgroup and PD group. FCIP patients who did not improve spontaneously showed a
clinical pattern similar to PD patients.
PMID- 25125484
TI - Medio-lateral balance impairment differentiates between Parkinson's disease and
atypical parkinsonism.
AB - In early disease stages, it can be difficult to differentiate clinically between
Parkinson's disease and the various forms of atypical parkinsonism, like multiple
system atrophy or progressive supranuclear palsy. Balance impairment in the medio
lateral plane (i.e. sideways) is often seen in patients with a form of atypical
parkinsonism, but not in patients with Parkinson's disease. This is reflected by
the distance between the feet during gait, which is typically normal (or even
narrow) in Parkinson's disease, but widened in atypical parkinsonism. Estimating
this stance width depends on subjective judgement, and is difficult to quantify
in clinical practice. Here, we emphasize that this medio-lateral balance
impairment can also be revealed using two simple tests: (1) inability to perform
tandem gait (taking one or more side steps being abnormal); and (2) self-report
by patients who have lost the ability to ride a bicycle. Both tests have a good
diagnostic yield in differentiating between Parkinson's disease and atypical
parkinsonism, even early in the course of the disease.
PMID- 25125485
TI - Tumor-associated macrophages as major players in the tumor microenvironment.
AB - During tumor progression, circulating monocytes and macrophages are actively
recruited into tumors where they alter the tumor microenvironment to accelerate
tumor progression. Macrophages shift their functional phenotypes in response to
various microenvironmental signals generated from tumor and stromal cells. Based
on their function, macrophages are divided broadly into two categories: classical
M1 and alternative M2 macrophages. The M1 macrophage is involved in the
inflammatory response, pathogen clearance, and antitumor immunity. In contrast,
the M2 macrophage influences an anti-inflammatory response, wound healing, and
pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble
the M2-polarized macrophages and are critical modulators of the tumor
microenvironment. Clinicopathological studies have suggested that TAM
accumulation in tumors correlates with a poor clinical outcome. Consistent with
that evidence, experimental and animal studies have supported the notion that
TAMs can provide a favorable microenvironment to promote tumor development and
progression. In this review article, we present an overview of mechanisms
responsible for TAM recruitment and highlight the roles of TAMs in the regulation
of tumor angiogenesis, invasion, metastasis, immunosuppression, and
chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a
promising novel strategy for an indirect cancer therapy.
PMID- 25125486
TI - Distinct networks of leptin- and insulin-sensing neurons regulate thermogenic
responses to nutritional and cold challenges.
AB - Defense of core body temperature (Tc) can be energetically costly; thus, it is
critical that thermoregulatory circuits are modulated by signals of energy
availability. Hypothalamic leptin and insulin signals relay information about
energy status and are reported to promote thermogenesis, raising the possibility
that they interact to direct an appropriate response to nutritional and thermal
challenges. To test this idea, we used an Nkx2.1-Cre driver to generate
conditional knockouts (KOs) in mice of leptin receptor (L(2.1)KO), insulin
receptor (I(2.1)KO), and double KOs of both receptors (D(2.1)KO). L(2.1)KOs are
hyperphagic and obese, whereas I(2.1)KOs are similar to controls. D(2.1)KOs
exhibit higher body weight and adiposity than L(2.1)KOs, solely due to reduced
energy expenditure. At 20-22 degrees C, fed L(2.1)KOs maintain a lower baseline
Tc than controls, which is further decreased in D(2.1)KOs. After an overnight
fast, some L(2.1)KOs dramatically suppress energy expenditure and enter a torpor
like state; this behavior is markedly enhanced in D(2.1)KOs. When fasted mice are
exposed to 4 degrees C, L(2.1)KOs and D(2.1)KOs both mount a robust thermogenic
response and rapidly increase Tc. These observations support the idea that
neuronal populations that integrate information about energy stores to regulate
the defense of Tc set points are distinct from those required to respond to a
cold challenge.
PMID- 25125487
TI - Loss-of-function mutations in ABCA1 and enhanced beta-cell secretory capacity in
young adults.
AB - Loss-of-function mutations affecting the cholesterol transporter ATP-binding
cassette transporter subfamily A member 1 (ABCA1) impair cellular cholesterol
efflux and are associated with reduced HDL-cholesterol (HDL-C) levels. ABCA1 may
also be important in regulating beta-cell cholesterol homeostasis and insulin
secretion. We sought to determine whether loss-of-function ABCA1 mutations affect
beta-cell secretory capacity in humans by performing glucose-potentiated arginine
tests in three subjects homozygous for ABCA1 mutations (age 25 +/- 11 years),
eight heterozygous subjects (28 +/- 7 years), and eight normal control subjects
pair-matched to the heterozygous carriers. To account for any effect of low HDL-C
on insulin secretion, we studied nine subjects with isolated low HDL-C with no
ABCA1 mutations (age 26 +/- 6 years) and nine pair-matched control subjects.
Homozygotes for ABCA1 mutations exhibited enhanced oral glucose tolerance and
dramatically increased beta-cell secretory capacity that was also greater in
ABCA1 heterozygous subjects than in control subjects, with no differences in
insulin sensitivity. Isolated low HDL-C subjects also demonstrated an increase in
beta-cell secretory capacity but in contrast to those with ABCA1 mutations,
exhibited impaired insulin sensitivity, supporting beta-cell compensation for
increased insulin demand. These data indicate that loss-of-function mutations in
ABCA1 in young adults may be associated with enhanced beta-cell secretory
capacity and normal insulin sensitivity and support the importance of cellular
cholesterol homeostasis in regulating beta-cell insulin secretion.
PMID- 25125489
TI - Public service stress and burnout over 12 months.
AB - BACKGROUND: Research indicates that workplace stress has the potential to harm
employee health with stress and stress-related absence increasing significantly
during economic recession and times of organizational change. AIMS: To explore
whether psychosocial hazards and burnout changed over a 12 month period in a
public sector organization during a period of severely reduced organizational
finances. METHODS: The Management Standards Indicator Tool (MSIT) and the Maslach
Burnout Inventory-General Scale (MBI-GS) were administered to employees of one
local government department in July 2011 and July 2012. RESULTS: A total of 128
employees completed the questionnaires in July 2011 (response rate 67%) and 57 in
July 2012 (response rate 54%). MSIT factor scores of demands, peer support and
role worsened significantly over the period of study. Furthermore, all
psychosocial hazards scored worse than the recommended level set by Health and
Safety Executive. Two burnout dimensions, 'demands' and 'cynicism', significantly
worsened over the 12 month period but professional efficacy increased.
CONCLUSIONS: The MSIT and MBI-GS appeared to have utility in this comparison.
Psychosocial hazards appeared to worsen over the 12 months of the study, as
'demands' and 'cynicism' increased. However, an increase in professional efficacy
was also seen, which requires further investigation.
PMID- 25125490
TI - Integrating attachment and depression in the confluence model of sexual assault
perpetration.
AB - This study sought to extend the confluence model of sexual assault perpetration
by examining attachment insecurity and depression as additional predictors of
sexual aggression. Male college students (N = 193) completed an online
questionnaire assessing confluence model constructs in addition to attachment and
history of depression. Overall, the model fit the data well, chi(2)(11, 193) =
19.43, p = ns; root mean square error of approximation = .063; comparative fit
index = .94. Attachment and depression demonstrated both direct and indirect
relationships with perpetration severity. The results contribute to elucidating
the process by which certain men become susceptible to perpetrating sexual
assault. Implications are discussed.
PMID- 25125488
TI - Mineralocorticoid receptor blockade improves coronary microvascular function in
individuals with type 2 diabetes.
AB - Reduced coronary flow reserve (CFR), an indicator of coronary microvascular
dysfunction, is seen in type 2 diabetes mellitus (T2DM) and predicts cardiac
mortality. Since aldosterone plays a key role in vascular injury, the aim of this
study was to determine whether mineralocorticoid receptor (MR) blockade improves
CFR in individuals with T2DM. Sixty-four men and women with well-controlled
diabetes on chronic ACE inhibition (enalapril 20 mg/day) were randomized to add
on therapy of spironolactone 25 mg, hydrochlorothiazide (HCTZ) 12.5 mg, or
placebo for 6 months. CFR was assessed by cardiac positron emission tomography at
baseline and at the end of treatment. There were significant and similar
decreases in systolic blood pressure with spironolactone and HCTZ but not with
placebo. CFR improved with treatment in the spironolactone group as compared with
the HCTZ group and with the combined HCTZ and placebo groups. The increase in CFR
with spironolactone remained significant after controlling for baseline CFR,
change in BMI, race, and statin use. Treatment with spironolactone improved
coronary microvascular function, raising the possibility that MR blockade could
have beneficial effects in preventing cardiovascular disease in patients with
T2DM.
PMID- 25125491
TI - Interview interruption and responses to questions about domestic violence in
India.
AB - This article uses the National Family Health Survey 2005-2006 (NFHS-3) of India
to examine the relationship between interview interruption and the reporting of
domestic violence. A sample of 65,610 currently married women was used to compare
reported acts of physical and sexual violence among women who had been
interrupted during their interview and those who had not. Logistic regression
analyses indicated that women whose interviews were interrupted by either an
adult man or woman were significantly more likely to report intimate partner
violence.
PMID- 25125492
TI - The explanatory role of relationship power and control in domestic violence
against women in Nicaragua: a feminist psychology analysis.
AB - This study offers a feminist psychology analysis of various aspects of
relationship power and control and their relative explanatory contribution to
understanding physical, psychological, and sexual violence against women.
Findings from structured interviews with 345 women from rural Nicaragua (M age =
44) overwhelmingly demonstrate that measures of power and control reflecting
interpersonal relationship dynamics have the strongest predictive power for
explaining violence when compared in multivariate analyses to several of the more
commonly used measures. These findings have implications for future research and
the evaluation of interventions designed to decrease levels of violence against
women.
PMID- 25125493
TI - Evaluation of the Green Dot Bystander Intervention to Reduce Interpersonal
Violence Among College Students Across Three Campuses.
AB - Evidence suggests that interventions to engage bystanders in violence prevention
increase bystander intentions and efficacy to intervene, yet the impact of such
programs on violence remains unknown. This study compared rates of violence by
type among undergraduate students attending a college campus with the Green Dot
bystander intervention (n = 2,768) with students at two colleges without
bystander programs (n = 4,258). Violent victimization rates were significantly (p
< .01) lower among students attending the campus with Green Dot relative to the
two comparison campuses. Violence perpetration rates were lower among males
attending the intervention campus. Implications of these results for research and
practice are discussed.
PMID- 25125494
TI - Extending Johnson's intimate partner violence typology: lessons from an
adolescent sample.
AB - Johnson's intimate partner violence (IPV) typology-categorizing IPV by both use
and receipt of physical violence and controlling behaviors-effectively predicts
IPV consequences among adults. His typology has not yet been applied to
adolescents, an important population for early IPV intervention. Therefore, in
analyzing IPV covariates among 493 female urban high school students, we used as
key predictors both Johnson's original typology and, for enhanced clarity, a
relationship-level extension. Preliminary evidence suggests that the pattern of
adolescent IPV differs substantially from that of adult IPV and that a
relationship-level typology provided additional clarity in categorizing this
pattern.
PMID- 25125495
TI - miR-1, miR-133a/b, and miR-208a in human fetal hearts correlate to the apoptotic
and proliferation markers.
AB - The heart is the first organ to function in the developing embryo. MicroRNAs
(miRNAs) are small non-coding RNAs involved in the translational regulation of
gene expression, which is beside transcriptional regulation crucial for the
morphologic development of muscle tissue. The aim of our study was to test the
hypothesis that the expression of miR-1, miR-133a/b, and miR-208a correlates with
gestational age as well as with an apoptotic and proliferative index in the
developing human heart. Our study included normal heart tissue samples obtained
at autopsy from 46 fetuses, 12 children, and 15 adults. Proliferation and
apoptosis were measured by the immunohistochemical detection of Ki67 and cleaved
CK18. Expression of miR-1, miR-133a, miR-133b, and miR-208a was measured using
real-time PCR. We found a similar level of expression of miR-133a/b in fetal and
children hearts that was different from the levels in healthy adults. We also
found a correlation between a miR-208a expression to the gestational age of
fetuses. We observed an inverse correlation between Ki67 expression and
gestational age. Expression of Ki67 was positively correlated to the expression
of miR-208a and miR-1, but inversely correlated to the expression of miR-133a/b.
Expression of cleaved-CK18 was also inversely correlated to the expression of miR
133a/b. Our results showed a general decrease in the expression of miR-1 and an
increase of miR-133a/b with increasing gestational age. We also found a general
decrease in the expression of miR-208a, mimicking the expression of its host
gene. Our results also suggest the involvement of miR-208a and miR-1 in the
proliferation as well as anti-proliferative and anti-apoptotic roles of miR
133a/b.
PMID- 25125496
TI - Combination of honokiol and magnolol inhibits hepatic steatosis through AMPK
SREBP-1 c pathway.
AB - Honokiol and magnolol, as pharmacological biphenolic compounds of Magnolia
officinalis, have been reported to have antioxidant and anti-inflammatory
properties. Sterol regulatory element binding protein-1 c (SREBP-1 c) plays an
important role in the development and processing of steatosis in the liver. In
the present study, we investigated the effects of a combination of honokiol and
magnolol on SREBP-1 c-dependent lipogenesis in hepatocytes as well as in mice
with fatty liver due to consumption of high-fat diet (HFD). Liver X receptor
alpha (LXRalpha) agonists induced activation of SREBP-1 c and expression of
lipogenic genes, which were blocked by co-treatment of honokiol and magnolol
(HM). Moreover, a combination of HM potently increased mRNA of fatty acid
oxidation genes. HM induced AMP-activated protein kinase (AMPK), an inhibitory
kinase of the LXRalpha-SREBP-1 c pathway. The role of AMPK activation induced by
HM was confirmed using an inhibitor of AMPK, Compound C, which reversed the
ability of HM to both inhibit SREBP-1 c induction as well as induce genes for
fatty acid oxidation. In mice, HM administration for four weeks ameliorated HFD
induced hepatic steatosis and liver dysfunction, as indicated by plasma
parameters and Oil Red O staining. Taken together, our results demonstrated that
a combination of HM has beneficial effects on inhibition of fatty liver and SREBP
1 c-mediated hepatic lipogenesis, and these events may be mediated by AMPK
activation.
PMID- 25125497
TI - Dengue virus infection induces broadly cross-reactive human IgM antibodies that
recognize intact virions in humanized BLT-NSG mice.
AB - The development of small animal models that elicit human immune responses to
dengue virus (DENV) is important since prior immunity is a major risk factor for
developing severe dengue disease. This study evaluated anti-DENV human antibody
(hAb) responses generated from immortalized B cells after DENV-2 infection in NOD
scid IL2rgamma(null) mice that were co-transplanted with human fetal thymus and
liver tissues (BLT-NSG mice). DENV-specific human antibodies predominantly of the
IgM isotype were isolated during acute infection and in convalescence. We found
that while a few hAbs recognized the envelope protein produced as a soluble
recombinant, a number of hAbs only recognized epitopes on intact virions. The
majority of the hAbs isolated during acute infection and in immune mice were
serotype-cross-reactive and poorly neutralizing. Viral titers in immune BLT-NSG
mice were significantly decreased after challenge with a clinical strain of
dengue. DENV-specific hAbs generated in BLT-NSG mice share some of the
characteristics of Abs isolated in humans with natural infection. Humanized BLT
NSG mice provide an attractive preclinical platform to assess the immunogenicity
of candidate dengue vaccines.
PMID- 25125498
TI - Phosphodiesterase 5 inhibitors augment UT-15C-stimulated ATP release from
erythrocytes of humans with pulmonary arterial hypertension.
AB - Both prostacyclin analogs and phosphodiesterase 5 (PDE5) inhibitors are effective
treatments for pulmonary arterial hypertension (PAH). In addition to direct
effects on vascular smooth muscle, prostacyclin analogs increase cAMP levels and
ATP release from healthy human erythrocytes. We hypothesized that UT-15C, an
orally available form of the prostacyclin analog, treprostinil, would stimulate
ATP release from erythrocytes of humans with PAH and that this release would be
augmented by PDE5 inhibitors. Erythrocytes were isolated and the effect of UT-15C
on cAMP levels and ATP release were measured in the presence and absence of the
PDE5 inhibitors, zaprinast or tadalafil. In addition, the ability of a soluble
guanylyl cyclase inhibitor to prevent the effects of tadalafil was determined.
Erythrocytes of healthy humans and humans with PAH respond to UT-15C with
increases in cAMP levels and ATP release. In both groups, UT-15C-induced ATP
release was potentiated by zaprinast and tadalafil. The effect of tadalafil was
prevented by pre-treatment with an inhibitor of soluble guanylyl cyclase in
healthy human erythrocytes. Importantly, UT-15C-induced ATP release was greater
in PAH erythrocytes than in healthy human erythrocytes in both the presence and
the absence of PDE5 inhibitors. The finding that prostacyclin analogs and PDE5
inhibitors work synergistically to enhance release of the potent vasodilator ATP
from PAH erythrocytes provides a new rationale for the co-administration of these
drugs in this disease. Moreover, these results suggest that the erythrocyte is a
novel target for future drug development for the treatment of PAH.
PMID- 25125499
TI - Ursodeoxycholyl lysophosphatidylethanolamide inhibits cholestasis- and hypoxia
induced apoptosis by upregulating antiapoptosis proteins.
AB - An increase of toxic bile acids such as glycochenodeoxycholic acid occurs during
warm ischemia reperfusion causing cholestasis and damage in hepatocytes and
intrahepatic biliary epithelial cells. We aim to test antiapoptosis effects of
ursodeoxycholyl lysophosphatidylethanolamide under cholestatic induction by
glycochenodeoxycholic acid treatment of mouse hepatocytes and hypoxia induction
by cobalt chloride treatment of intrahepatic biliary epithelial cancer Mz-ChA
1cell line. Such treatments caused marked increases in apoptosis as evidenced by
activation of caspase 3, caspase 8 and poly (ADP-ribose) polymerase-1. Co
treatment with ursodeoxycholyl lysophosphatidylethanolamide significantly
inhibited these increases. Interestingly, ursodeoxycholyl
lysophosphatidylethanolamide was able to increase expression of antiapoptotic
cellular FLICE-inhibitory protein in both cell types. Ursodeoxycholyl
lysophosphatidylethanolamide also prevented the decreases of myeloid cell
leukemia sequence-1 protein in both experimental systems, and this protection was
due to ursodeoxycholyl lysophosphatidylethanolamide's ability to inhibit
ubiquitination-mediated degradation of myeloid cell leukemia sequence-1, and to
increase the phosphorylation of GSK-3beta. In addition, ursodeoxycholyl
lysophosphatidylethanolamide was able to prevent the decreased expression of
another antiapoptotic cellular inhibitor of apoptosis 2 in cobalt chloride
treated Mz-ChA-1 cells. Hence, ursodeoxycholyl lysophosphatidylethanolamide
mediated cytoprotection against apoptosis during toxic bile-acid and ischemic
stresses by a mechanism involving accumulation of cellular FLICE-inhibitory
protein, myeloid cell leukemia sequence-1 and cellular inhibitor of apoptosis 2
proteins. Ursodeoxycholyl lysophosphatidylethanolamide may thus be used as an
agent to prevent hepatic ischemia reperfusion.
PMID- 25125500
TI - Preparation and antitumor effect of a toxin-linked conjugate targeting vascular
endothelial growth factor receptor and urokinase plasminogen activator.
AB - The aberrant signaling activation of vascular endothelial growth factor receptor
(VEGFR) and urokinase plasminogen activator (uPA) is a common characteristic of
many tumors, including lung cancer. Accordingly, VEGFR and uPA have emerged as
attractive targets for tumor. KDR (Flk-1/VEGFR-2), a member of the VEGFR family,
has been recognized as an important target for antiangiogenesis in tumor. In this
study, a recombinant immunotoxin was produced to specifically target KDR
expressing tumor vascular endothelial cells and uPA-expressing tumor cells and
mediate antitumor angiogenesis and antitumor effect. Based on its potent
inhibitory effect on protein synthesis, Luffin-beta (Lbeta) ribosome-inactivating
protein was selected as part of a recombinant fusion protein, a single-chain
variable fragment against KDR (KDRscFv)-uPA cleavage site (uPAcs)-Lbeta-KDEL
(named as KPLK). The KDRscFv-uPAcs-Lbeta-KDEL (KPLK) contained a single-chain
variable fragment (scFv) against KDR, uPAcs, Lbeta, and the retention signal for
endoplasmic reticulum proteins KDEL (Lys-Asp-Glu-Leu). The KPLK-expressing vector
was expressed in Escherichia coli, and the KPLK protein was isolated with nickel
affinity chromatography and gel filtration chromatography. Sodium dodecyl sulfate
polyacrylamide gel electrophoresis test demonstrated KPLK was effectively
expressed. Result of in vitro cell viability assay on non-small cell lung cancer
(NSCLC) H460 cell line (uPA-positive cell) revealed that KPLK significantly
inhibited cell proliferation, induced apoptosis, and accumulated cells in S and
G2/M phases, but the normal cell line (human submandibular gland cell) was
unaffected. These effects were enhanced when uPA was added to digest KPLK to
release Lbeta. For in vivo assay of KPLK, subcutaneous xenograft tumor model of
nude mice were established with H460 cells. Growth of solid tumors was
significantly inhibited in animals treated with KPLK up to 21 days, tumor weights
were decreased, and the expression of angiogenesis marker CD31 was downregulated;
meanwhile, the apoptosis-related protein casspase-3 was upregulated. These
results suggested that the recombinant KPLK may have therapeutic applications on
tumors, especially uPA-overexpressing ones.
PMID- 25125502
TI - Effect of perceived stress on cytokine production in healthy college students.
AB - Chronic psychological stress impairs antibody synthesis following influenza
vaccination. Chronic stress also increases circulating levels of proinflammatory
cytokines and glucocorticoids in elders and caregivers, which can impair antibody
synthesis. The purpose of this study was to determine whether psychological
stress increases ex vivo cytokine production or decreases glucocorticoid
sensitivity (GCS) of peripheral blood leukocytes from healthy college students. A
convenience sample of Reserve Officer Training Corps (ROTC) students completed
the Perceived Stress Scale (PSS). Whole blood was incubated in the presence of
influenza vaccine and dexamethasone to evaluate production of interleukin-6 (IL
6), interleukin-1-beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and
interferon-gamma (IFN-gamma). Multiple regression models controlling for age,
gender, and grade point average revealed a negative relationship between PSS and
GCS for vaccine-stimulated production of IL-1beta, IL-6, and TNF-alpha. These
data increase our understanding of the complex relationship between chronic
stress and immune function.
PMID- 25125501
TI - Telmisartan induces apoptosis and regulates Bcl-2 in human renal cancer cells.
AB - It has been well-characterized that the renin-angiotensin system (RAS)
physiologically regulates systemic arterial pressure. However, RAS signaling has
also been shown to increase cell proliferation during malignancy, and angiotensin
receptor blockers (ARBs) are able to decrease pro-survival signaling by
inhibiting anti-apoptotic molecules and suppressing caspase activity. In this
study, the apoptotic effects of telmisartan, a type of ARB, was evaluated using a
non-cancerous human renal cell line (HEK) and a human renal cell carcinoma (RCC)
cell line (786). Both types of cells were treated with telmisartan for 4 h, 24 h,
and 48 h, and then were assayed for levels of apoptosis, caspase-3, and Bcl-2
using MTT assays, flow cytometry, and immunostaining studies. Analysis of
variance was used to identify significant differences between these data (P <
0.05). Following the treatment of 786 cells with 100 uM and 200 uM telmisartan, a
marked inhibition of cell proliferation was observed. 50 uM cisplatin also caused
high inhibition of these cells. Moreover, these inhibitions were both
concentration- and time-dependent (P < 0.05). Various apoptotic effects were also
observed compared with control cells at the 24 h and 48 h timepoints assayed (P <
0.001). Furthermore, positive caspase-3 staining and down-regulation of Bcl-2
were detected, consistent with induction of cell death. In contrast, treatment of
HEK cells with telmisartan did not produce an apoptotic effect compared with
control cells at the 24 h timepoint (P > 0.05). Treatment with cisplatin promoted
in HEK cells high index of apoptosis (P < 0.001). Taken together, these results
suggest that telmisartan induces apoptosis via down-regulation of Bcl-2 and
involvement of caspase-3 in human RCC cells.
PMID- 25125503
TI - Tomato fruit chromoplasts behave as respiratory bioenergetic organelles during
ripening.
AB - During tomato (Solanum lycopersicum) fruit ripening, chloroplasts differentiate
into photosynthetically inactive chromoplasts. It was recently reported that
tomato chromoplasts can synthesize ATP through a respiratory process called
chromorespiration. Here we show that chromoplast oxygen consumption is stimulated
by the electron donors NADH and NADPH and is sensitive to octyl gallate (Ogal), a
plastidial terminal oxidase inhibitor. The ATP synthesis rate of isolated
chromoplasts was dependent on the supply of NAD(P)H and was fully inhibited by
Ogal. It was also inhibited by the proton uncoupler carbonylcyanide m
chlorophenylhydrazone, suggesting the involvement of a chemiosmotic gradient. In
addition, ATP synthesis was sensitive to 2,5-dibromo-3-methyl-6-isopropyl-p
benzoquinone, a cytochrome b6f complex inhibitor. The possible participation of
this complex in chromorespiration was supported by the detection of one of its
components (cytochrome f) in chromoplasts using immunoblot and immunocytochemical
techniques. The observed increased expression of cytochrome c6 during ripening
suggests that it could act as electron acceptor of the cytochrome b6f complex in
chromorespiration. The effects of Ogal on respiration and ATP levels were also
studied in tissue samples. Oxygen uptake of mature green fruit and leaf tissues
was not affected by Ogal, but was inhibited increasingly in fruit pericarp
throughout ripening (up to 26% in red fruit). Similarly, Ogal caused a
significant decrease in ATP content of red fruit pericarp. The number of
energized mitochondria, as determined by confocal microscopy, strongly decreased
in fruit tissue during ripening. Therefore, the contribution of chromoplasts to
total fruit respiration appears to increase in late ripening stages.
PMID- 25125505
TI - Beneficial effect of pistachio consumption on glucose metabolism, insulin
resistance, inflammation, and related metabolic risk markers: a randomized
clinical trial.
AB - OBJECTIVE: To examine whether a pistachio-rich diet reduces the prediabetes stage
and improves its metabolic risk profile. RESEARCH DESIGN AND METHODS: Prediabetic
subjects were recruited to participate in this Spanish randomized clinical trial
between 20 September 2011 and 4 February 2013. In a crossover manner, 54 subjects
consumed two diets, each for 4 months: a pistachio-supplemented diet (PD) and a
control diet (CD). A 2-week washout period separated study periods. Diets were
isocaloric and matched for protein, fiber, and saturated fatty acids. A total of
55% of the CD calories came from carbohydrates and 30% from fat, whereas for the
PD, these percentages were 50 and 35%, respectively (including 57 g/day of
pistachios). RESULTS: Fasting glucose, insulin, and HOMA of insulin resistance
decreased significantly after the PD compared with the CD. Other cardiometabolic
risk markers such as fibrinogen, oxidized LDL, and platelet factor 4
significantly decreased under the PD compared with the CD (P < 0.05), whereas
glucagon-like peptide-1 increased. Interleukin-6 mRNA and resistin gene
expression decreased by 9 and 6%, respectively, in lymphocytes after the
pistachio intervention (P < 0.05, for PD vs. CD). SLC2A4 expression increased by
69% in CD (P = 0.03, for PD vs. CD). Cellular glucose uptake by lymphocytes
decreased by 78.78% during the PD (P = 0.01, PD vs. CD). CONCLUSIONS: Chronic
pistachio consumption is emerging as a useful nutritional strategy for the
prediabetic state. Data suggest that pistachios have a glucose- and insulin
lowering effect, promote a healthier metabolic profile, and reverse certain
metabolic deleterious consequences of prediabetes.
PMID- 25125504
TI - Beyond the barrier: communication in the root through the endodermis.
AB - The root endodermis is characterized by the Casparian strip and by the suberin
lamellae, two hydrophobic barriers that restrict the free diffusion of molecules
between the inner cell layers of the root and the outer environment. The presence
of these barriers and the position of the endodermis between the inner and outer
parts of the root require that communication between these two domains acts
through the endodermis. Recent work on hormone signaling, propagation of calcium
waves, and plant-fungal symbiosis has provided evidence in support of the
hypothesis that the endodermis acts as a signaling center. The endodermis is also
a unique mechanical barrier to organogenesis, which must be overcome through
chemical and mechanical cross talk between cell layers to allow for development
of new lateral organs while maintaining its barrier functions. In this review, we
discuss recent findings regarding these two important aspects of the endodermis.
PMID- 25125506
TI - Efficacy and safety of oral methazolamide in patients with type 2 diabetes: a 24
week, placebo-controlled, double-blind study.
AB - OBJECTIVE: To evaluate the safety and efficacy of methazolamide as a potential
therapy for type 2 diabetes. RESEARCH DESIGN AND METHODS: This double-blind,
placebo-controlled study randomized 76 patients to oral methazolamide (40 mg
b.i.d.) or placebo for 24 weeks. The primary efficacy end point for methazolamide
treatment was a placebo-corrected reduction in HbA1c from baseline after 24 weeks
(DeltaHbA1c). RESULTS: Mean +/- SD baseline HbA1c was 7.1 +/- 0.7% (54 +/- 5
mmol/mol; n = 37) and 7.4 +/- 0.6% (57 +/- 5 mmol/mol; n = 39) in the
methazolamide and placebo groups, respectively. Methazolamide treatment was
associated with a DeltaHbA1c of -0.39% (95% CI -0.82, 0.04; P < 0.05) (-4.3
mmol/mol [-9.0, 0.4]), an increase in the proportion of patients achieving HbA1c
<=6.5% (48 mmol/mol) from 8 to 33%, a rapid reduction in alanine aminotransferase
(~10 units/L), and weight loss (2%) in metformin-cotreated patients. CONCLUSIONS:
Methazolamide is the archetype for a new intervention in type 2 diabetes with
clinical benefits beyond glucose control.
PMID- 25125507
TI - Brain iron overload, insulin resistance, and cognitive performance in obese
subjects: a preliminary MRI case-control study.
AB - OBJECTIVE: The linkage among the tissue iron stores, insulin resistance (IR), and
cognition remains unclear in the obese population. We aimed to identify the
factors that contribute to increased hepatic iron concentration (HIC) and brain
iron overload (BIO), as evaluated by MRI, and to evaluate their impact on
cognitive performance in obese and nonobese subjects. RESEARCH DESIGN AND
METHODS: We prospectively recruited 23 middle-aged obese subjects without
diabetes (13 women; age 50.4 +/- 7.7 years; BMI 43.7 +/- 4.48 kg/m2) and 20
healthy nonobese volunteers (10 women; age 48.8 +/- 9.5 years; BMI 24.3 +/- 3.54
kg/m2) in whom iron load was assessed in white and gray matter and the liver by
MRI. IR was measured from HOMA-IR and an oral glucose tolerance test. A battery
of neuropsychological tests was used to evaluate the cognitive performance.
Multivariate regression analysis was used to identify the independent
associations of BIO and cognitive performance. RESULTS: A significant increase in
iron load was detected at the caudate nucleus (P < 0.001), lenticular nucleus (P
= 0.004), hypothalamus (P = 0.002), hippocampus (P < 0.001), and liver (P <
0.001) in obese subjects. There was a positive correlation between HIC and BIO at
caudate (r = 0.517, P < 0.001), hypothalamus (r = 0.396, P = 0.009), and
hippocampus (r = 0.347, P < 0.023). The area under the curve of insulin was
independently associated with BIO at the caudate (P = 0.001), hippocampus (P =
0.028), and HIC (P = 0.025). BIOs at the caudate (P = 0.028), hypothalamus (P =
0.006), and lenticular nucleus (P = 0.012) were independently associated with
worse cognitive performance. CONCLUSIONS: Obesity and IR may contribute to
increased HIC and BIO being associated with worse cognitive performance. BIO
could be a potentially useful MRI biomarker for IR and obesity-associated
cognitive dysfunction.
PMID- 25125508
TI - Impact of a community health workers-led structured program on blood glucose
control among latinos with type 2 diabetes: the DIALBEST trial.
AB - OBJECTIVE: Latinos with type 2 diabetes (T2D) face major healthcare access and
disease management disparities. We examined the impact of the Diabetes Among
Latinos Best Practices Trial (DIALBEST), a community health worker (CHW)-led
structured intervention for improving glycemic control among Latinos with T2D.
RESEARCH DESIGN AND METHODS: A total of 211 adult Latinos with poorly controlled
T2D were randomly assigned to a standard of healthcare (n = 106) or CHW (n = 105)
group. The CHW intervention comprised 17 individual sessions delivered at home by
CHWs over a 12-month period. Sessions addressed T2D complications, healthy
lifestyles, nutrition, healthy food choices and diet for diabetes, blood glucose
self-monitoring, and medication adherence. Demographic, socioeconomic, lifestyle,
anthropometric, and biomarker (HbA1c, fasting blood glucose, and lipid profile)
data were collected at baseline and 3, 6, 12, and 18 months (6 months
postintervention). Groups were equivalent at baseline. RESULTS: Participants had
high HbA1c at baseline (mean 9.58% [81.2 mmol/mol]). Relative to participants in
the control group, CHWs had a positive impact on net HbA1c improvements at 3
months (-0.42% [-4.62 mmol/mol]), 6 months (-0.47% [-5.10 mmol/mol]), 12 months (
0.57% [-6.18 mmol/mol]), and 18 months (-0.55% [-6.01 mmol/mol]). The overall
repeated-measures group effect was statistically significant (mean difference
0.51% [-5.57 mmol/mol], 95% CI -0.83, -0.19% [-9.11, -2.03 mmol/mol], P = 0.002).
CHWs had an overall significant effect on fasting glucose concentration that was
more pronounced at the 12- and 18-month visits. There was no significant effect
on blood lipid levels, hypertension, and weight. CONCLUSIONS: DIALBEST is an
effective intervention for improving blood glucose control among Latinos with
T2D.
PMID- 25125511
TI - The role of non-governmental organizations in residential solid waste management:
a case study of Puducherry, a coastal city of India.
AB - Poorly planned and uncontrolled urbanization in India has caused a variety of
negative, often irreversible, environmental impacts. The impacts appear to be
unavoidable and not easily mitigable due to the mounting public health problems
caused by non-segregation of solid wastes at source and their subsequent improper
management. Recently in India, non-governmental organizations (NGOs) and other
civil society organizations have increasingly started to get involved in
improving waste management services. Municipal solid waste management being a
governmental function, the contribution of NGOs in this field has not been well
documented. This study highlights the activities and services of Shuddham, an NGO
functioning in the town of Puducherry within the Union Territory of Puducherry in
South India. The NGO program promoted much needed awareness and education,
encouraged source separation, enhanced door-to-door collection, utilized wastes
as raw materials and generated more job opportunities. Even though source
separation prior to door-to-door collection is a relatively new concept, a
significant percentage of residents (39%) in the study area participated fully,
while a further 48% participated in the collection service. The average amount of
municipal solid waste generated by residential units in the Raj Bhavan ward was
8582 kg/month of which 47% was recovered through active recycling and composting
practices. The study describes the features and performance of NGO-mediated solid
waste management, and evaluates the strengths and weaknesses as well as the
opportunities and threats of this system to see whether this model can
sustainably replace the low-performance conventional solid waste management in
practice in the town of Puducherry. The experiences from this case study are
expected to provide broad guidelines to better understand the role of NGOs and
their contributions towards sustainable waste management practices in urban
areas.
PMID- 25125510
TI - Enhancing biogas production from anaerobic biodegradation of the organic fraction
of municipal solid waste through leachate blending and recirculation.
AB - Leachate recirculation has a profound advantage on biodegradation of the organic
fraction of municipal solid waste in landfills. Mature leachate from older
sections of landfills (>10 years) and young leachate were blended and added to
organic fraction of municipal solid waste in a series of biomethane potential
assay experiments with different mixing ratios of mature and young leachate and
their effect on biogas production was monitored. The improvement in biogas
production was in the range of 19%-41% depending on the ratio of mixing old and
new leachate. The results are conclusive that the biogas generation could be
improved by blending the old and new leachate in a bioreactor landfill system as
compared with a conventional system employed in bioreactor landfills today for
recirculating the same age leachate.
PMID- 25125512
TI - Calcaneal "Z" osteotomy effect on hindfoot varus after triple arthrodesis in a
cadaver model.
AB - BACKGROUND: Triple arthrodesis involves subtalar, talonavicular, and
calcaneocuboid joint fusion and is performed to relieve pain and correct
deformity. Complications include malunion resulting in equinovarus and lateral
column overload, which can lead to painful callosities and stress fractures. This
study quantified the effectiveness of a closing-wedge calcaneal "Z" osteotomy for
correction of the varus condition and reduction of abnormal loading of the
lateral border of the foot. METHODS: Ten fresh-frozen feet were used. Angle
meters were attached to the calcaneus and second cuneiform to measure hindfoot
and midfoot varus, and pressure sensors were placed under the first and fifth
metatarsal heads to document loading of the borders of the foot. Tensile loads
were applied to ten extrinsic tendons and the Achilles tendon while an 1187 N
axial foot load was applied. Calcaneus and second cuneiform coronal plane angles
and medial and lateral plantar pressures were measured initially, after triple
fusion-induced varus, and after "Z" osteotomy. RESULTS: The calcaneal "Z"
osteotomy had no significant corrective effect, with hindfoot alignment virtually
identical before and after the procedure under the described foot loading
conditions. Similarly, second cuneiform inclination, representative of midfoot
alignment, showed no change from the osteotomy. Medial and lateral peak plantar
pressures after calcaneal "Z" osteotomy did not differ from those measured after
varus triple fusion. CONCLUSION: In this cadaver model of varus malunited triple
arthrodesis, the closing-wedge calcaneal "Z" osteotomy was ineffective for
correction of bone alignment and lateral forefoot overloading under the tested
conditions. CLINICAL RELEVANCE: The results provide additional information on
which to base treatment after triple arthrodesis with varus malunion.
PMID- 25125513
TI - Comparison of nonlocking plates and locking plates for intraarticular calcaneal
fracture.
AB - BACKGROUND: The optimal treatment of displaced intraarticular calcaneal fractures
remains challenging. Currently, there is no uniform method to treat such
fractures. The purpose of this study was to compare the radiographic and clinical
outcome of nonlocking plates and locking plates in the treatment of
intraarticular calcaneal fractures. METHODS: A retrospective comparative study
was performed including 42 patients with intraarticular calcaneal fractures that
were treated by nonlocking plate (n = 18) or locking plates (n = 24) between
January 2010 and June 2012. Radiological and functional outcomes were compared
between the 2 groups. RESULTS: At the final follow-up, all fractures were healed,
and the patients with a locking plate had a significantly better Bohler's angle
and Gissane's angle compared with the nonlocking plate group (P < .05). No
complications occurred for the patients in the locking plate group, and 3
patients in the nonlocking plate group had implant loosening that led to loss of
reduction (P < .05). The average American Orthopaedic Foot and Ankle Society
hindfoot score in the locking plate group was significantly higher than that in
the nonlocking plate group (P < .05). No statistically significant difference
between the 2 groups was found regarding SF-36 (P > .05). CONCLUSION: This study
supports the view that locking plates may provide better stability and functional
recovery in the treatment of intraarticular calcaneal fractures. LEVEL OF
EVIDENCE: Level III, comparative case series.
PMID- 25125509
TI - Molecular architecture of mammalian nitric oxide synthases.
AB - NOSs are homodimeric multidomain enzymes responsible for producing NO. In
mammals, NO acts as an intercellular messenger in a variety of signaling
reactions, as well as a cytotoxin in the innate immune response. Mammals possess
three NOS isoforms--inducible, endothelial, and neuronal NOS--that are composed
of an N-terminal oxidase domain and a C-terminal reductase domain. Calmodulin
(CaM) activates NO synthesis by binding to the helical region connecting these
two domains. Although crystal structures of isolated domains have been reported,
no structure is available for full-length NOS. We used high-throughput single
particle EM to obtain the structures and higher-order domain organization of all
three NOS holoenzymes. The structures of inducible, endothelial, and neuronal NOS
with and without CaM bound are similar, consisting of a dimerized oxidase domain
flanked by two separated reductase domains. NOS isoforms adopt many conformations
enabled by three flexible linkers. These conformations represent snapshots of the
continuous electron transfer pathway from the reductase domain to the oxidase
domain, which reveal that only a single reductase domain participates in electron
transfer at a time, and that CaM activates NOS by constraining rotational motions
and by directly binding to the oxidase domain. Direct visualization of these
large conformational changes induced during electron transfer provides
significant insight into the molecular underpinnings governing NO formation.
PMID- 25125515
TI - European Restart a Heart Day.
PMID- 25125514
TI - Transdermal glyceryl trinitrate in the treatment of ischemia following toe
deformity correction: a case series.
PMID- 25125517
TI - Towards evidence-based emergency medicine: best BETs from the Manchester Royal
Infirmary . BET 1: Do patients with an asymptomatic sub-segmental pulmonary
embolism need anticoagulation therapy?
AB - A short cut review was carried out to establish whether therapeutic
anticoagulation is required for patients who have an incidental diagnosis of
subsegmental pulmonary embolism (PE), which is asymptomatic. 4 studies were
relevant to the three-part question. The author, date and country of publication,
patient group studied, study type, relevant outcomes, results and study
weaknesses of these papers are tabulated. The evidence suggests that patients
with clinically unsuspected PE may have better prognostic outcomes than those
with symptomatic presentations, especially if the PE is at the sub-segmental
level. The only direct comparison of anti-coagulation versus no anti-coagulation
in patients with an asymptomatic, unsuspected PE suggests a survival benefit from
anti-coagulation. However, this study included patients with cancer and was not
restricted to patients with subsegmental PE. Consequently, the clinical bottom
line is that level 1 evidence is required to answer this question. In the
meantime decisions must continue to be informed by clinical judgment.
PMID- 25125516
TI - Chinese bystanders in medical emergencies: apathetic or bewildered?
PMID- 25125519
TI - Towards evidence-based emergency medicine: best BETs from the Manchester Royal
Infirmary. BET 2: the use of local anaesthetic lubrication for the
catheterisation of males.
AB - A short cut review was carried out to establish whether local anaesthetic
lubrication is necessary for urethral catheterisation in men. Two studies were
directly relevant to the question. The author, date and country of publication,
patient group studied, study type, relevant outcomes, results and study
weaknesses of these papers are tabulated. The clinical bottom line is that the
use of local anaesthetic is effective in this population and should form part of
the procedure.
PMID- 25125551
TI - Moving the worksite health promotion profession forward: is the time right for
requiring standards? A review of the literature.
AB - Standards in any profession are adopted to assure that the individuals hired are
adequately trained and the programs that they oversee are of the highest quality.
Worksite health promotion should be no different from any other field. A review
of the research conducted by experts in worksite health promotion is examined,
along with an assessment of skills needed to ensure that wellness programs are
effective and employees, their families, and even their communities are educated
on the ways to best prevent chronic diseases and occupational incidences through
healthy and safe behaviors. This article is consistent with Health Promotion
Practice's mission and focuses on the exploration of the processes used to plan
effective worksite health promotion programs, and it suggests initial discussions
on whether these processes should become standards for professionals in the
worksite health promotion field.
PMID- 25125552
TI - When 4.5 million people become patients.
PMID- 25125553
TI - Relvar Ellipta for asthma.
AB - ?Relvar Ellipta (GSK) is a dry powder inhaler that contains a corticosteroid
(fluticasone furoate) and a long-acting beta2 agonist (vilanterol trifenatate).
It is licensed for once-daily use as maintenance therapy for chronic obstructive
pulmonary disease (COPD) and asthma. In a previous article we considered its use
in the management of COPD.1 Here we review the evidence for Relvar Ellipta in the
treatment of patients with asthma.
PMID- 25125554
TI - 'Evolution-proofing' antibacterials.
PMID- 25125556
TI - Any detectable thyroglobulin in lymph node biopsy washouts suggests local
recurrence in differentiated thyroid cancer.
AB - The sensitivity of local recurrence detection in differentiated thyroid cancer
(DTC) is increased by measuring thyroglobulin in needle washouts from lymph node
fine-needle aspiration biopsies (FNA-Tg). Recent studies have proposed minimum
diagnostic threshold values for FNA-Tg and have reported interference from Tg
antibodies (Tg Ab), leading to low or false-negative results. The aim of this
study was to assess the utility of FNA-Tg in the diagnosis of local DTC
recurrence in patients referred to a single pathology service used by our
tertiary teaching hospital, the first such study in an Australian cohort. Data
were collected from the pathology service database for FNA-Tg over an 18-month
period, and the results of 69 FNA-Tg samples from 57 patients were obtained. FNA
Tg findings were compared with cytology and histology when patients proceeded to
surgery. Using the functional sensitivity as the cut-off, detectable FNA-Tg
(>=0.9 MUg/l) had a sensitivity of 95.7%, specificity of 50% and positive
predictive value of 95.7%. Our results suggest that detectable FNA-Tg leads to
histological confirmation of local nodal DTC recurrence and would support a
decision to proceed to surgery. Serum Tg Ab can, however, interfere with FNA-Tg
measurements. Thus, we now recommend routine use of FNA-Tg washouts in all lymph
node FNA biopsies for the detection of DTC recurrence.
PMID- 25125555
TI - Management of insulin pump therapy in children with type 1 diabetes.
AB - Insulin pump therapy is a current treatment option for children and adolescents
with type 1 diabetes. Insulin pumps can provide a greater flexibility in insulin
administration and meal planning, as compared with multiple insulin injections,
and they may be particularly suitable for the paediatric age group. Many young
people with diabetes have integrated insulin pumps into their daily practice. The
use of insulin pumps can also be supplemented by the information retrieved from
continuous glucose monitoring in the sensor-augmented pump therapy, which may
improve glycaemic control. In this review, we describe the principles of pump
therapy and summarise features of commercially available insulin pumps, with
focus on practical management and the advantages and disadvantages of this
technology.
PMID- 25125557
TI - Corticosterone metabolites in laying hen droppings-Effects of fiber enrichment,
genotype, and daily variations.
AB - There is growing interest and concern for animal welfare in commercial poultry
production. To evaluate stress and welfare in an objective and noninvasive way,
fecal corticosterone metabolites (FCM) in droppings can be analyzed. However, the
influence of diet, genotype, and daily variations in FCM and production of
droppings in laying hens has been poorly investigated. This study examined the
effect of insoluble fiber by adding 3% ground straw pellets to the feed to
Lohmann Selected Leghorn (LSL) and Lohmann Brown (LB) hens housed in furnished
cages between 20 and 40 wk of age. In total, 960 hens were included in the study.
Droppings were collected 4 times per day for 3 consecutive days and analyzed by
corticosterone immunoassay. Biological validation confirmed the ability of the
assay to detect changes in FCM levels. Inclusion of straw pellets in the feed
increased FCM concentration in both hen genotypes and increased excretion rate of
FCM in LB hens. The LB hens also produced greater amounts of droppings than LSL
hens. Both FCM levels and production of droppings varied during the day, although
no distinct diurnal rhythm was found. These findings demonstrate that when using
FCM to evaluate stress and welfare in laying hens, many factors (e.g., diet,
genotype used, and so on) need to be taken into account to allow accurate
interpretation of the results. In addition, under certain conditions, excretion
rate of FCM might be more appropriate to use compared with FCM concentration.
PMID- 25125558
TI - The effect of perch availability during pullet rearing and egg laying on the
behavior of caged White Leghorn hens.
AB - Enriched cages, compared with conventional cages, allow egg laying strains of
chickens to meet some behavioral needs, including a high motivation to perch. The
objective of this study was to determine if perch availability during rearing
affected perch use as adults and if perch presence affected eating and drinking
in caged White Leghorn hens. Chickens were assigned to 14 cages each with and
without 2 round metal perches from hatch to 16.9 wk of age. At 17 wk of age,
pullets were assigned to laying cages consisting of 1 of 4 treatments. Treatment
1 chickens never had access to perches (controls). Treatment 2 chickens only had
access to 2 round metal perches during the laying phase (17 to 71 wk of age).
Treatment 3 chickens only had access to 2 round perches during the pullet phase
(0 to 16.9 wk of age). Treatment 4 chickens had access to the perches during both
the pullet and laying phase. Each treatment during the adult phase consisted of 9
cages with 9 birds/cage for a total of 36 cages. Automatic infrared cameras were
used to monitor behavior of hens in each cage for a 24-h period at 19, 24, 29,
34, 39, 44, 49, 54, 59, 64, and 69 wk of age. Behavior was also recorded twice
weekly by an observer in the room where the hens were housed during photophase
from 25 to 68 wk of age. Behavioral data were analyzed using ANOVA with repeated
measures and the MIXED model procedure. A greater proportion of hens without
perches as pullets used the rear perch more during both photophase and scotophase
than hens with prior pullet perching experience. Eating and drinking activities
of caged adult Leghorns were not impaired by their prior experience to perches as
pullets or by the presence of perches in laying cages. It is concluded that
providing perches in cages to White Leghorns during pullet rearing did not
facilitate use of perches as adults.
PMID- 25125559
TI - Enhanced immune responses of chickens to oral vaccination against infectious
bursal disease by ginseng stem-leaf saponins.
AB - Infectious bursal disease (IBD), caused by infectious bursal disease virus
(IBDV), is an immunosuppressive infectious disease of global economic importance
in poultry. This study was designed to evaluate the effect of oral administration
of ginseng stem-leaf saponins (GSLS) on humoral and gut mucosal immunity in
chickens vaccinated with live IBDV vaccine, and furthermore, to test its
protective efficacy against virulent IBDV challenge following vaccination. In
experiment 1, chickens were orally administered with GSLS at 5 mg/kg of BW for 7
d, and then immunized with live IBDV vaccine via the oral route. Serum was
sampled on 0, 1, 2, 3, 4, and 5 wk postvaccination for detecting antibody titers
by ELISA, and intestinal tissues were collected on 0, 1, 3, and 5 wk
postvaccination for measurement of IgA-positive cells and intestinal
intraepithelial lymphocytes by immunohistochemical and hematoxylin-eosin
staining, respectively. Result showed that antibody titers, IgA-positive cells
and intestinal intraepithelial lymphocytes were significantly higher in chickens
drinking GSLS than the control, suggesting an enhanced effect of GSLS on humoral
and gut mucosal immune responses. In experiment 2, chickens were delivered with
GSLS and then vaccinated in the same way as in experiment 1. The birds were
challenged with virulent IBDV at wk 3 postvaccination. Then the birds were
weighed, bled, and necropsied at d 3 postchallenge and the bursae were sampled
for gross and histopathological examination. Results demonstrated that GSLS
provided a better protection against virulent IBDV challenge following
vaccination than the control. In conclusion, oral administration of GSLS enhances
both humoral and gut mucosal immune responses to IBDV and offers a better
protection against virulent IBDV challenge. Considering its immunomodulatory
properties to IBDV vaccine, GSLS might be a promising oral adjuvant for
vaccination against infectious diseases in poultry.
PMID- 25125560
TI - Nutrient analysis, metabolizable energy, and digestible amino acids of soybean
meals of different origins for broilers.
AB - Nutrient composition, ileal amino acid (AA) digestibility, and AME of 55 soybean
meal (SBM) samples from the United States (US; n = 16), Argentina (ARG; n = 16),
Brazil (BRA; n = 10), and India (IND; n = 13), collected from commercial mills in
Southeast Asia, were compared using laboratory analyses and animal studies. There
were significant (P < 0.05 to 0.001) differences due to origin in CP, fat, ash,
fiber, and nonstarch polysaccharide (NSP) contents of SBM. The average CP content
of US, ARG, BRA, and IND samples was determined to be 47.3, 46.9, 48.2, and 46.4%
(as-fed basis), respectively. Compared with SBM from other origins, crude fiber
and NSP contents were lower (P < 0.05) and sucrose content was higher (P < 0.05)
in the US samples. The IND samples had the highest (P < 0.05) contents of fiber,
ash, and NSP, and lowest (P < 0.05) contents of fat and sucrose. Differences (P <
0.0001) were observed among origins for in vitro protein quality measures (urease
index, KOH protein solubility, and trypsin inhibitor activity). Significant (P <
0.001) effects due to origin were observed for all minerals. Soybean meal from
the US and IND had higher (P < 0.05) calcium contents (0.45%) compared with those
from ARG and BRA (0.28-0.31%). Phosphorus and potassium contents were lowest (P <
0.05) in SBM from IND, and no differences (P > 0.05) were observed in SBM from
other origins. Iron content was markedly high (928 mg/kg) in SBM from IND
compared with those from other origins (103-134 mg/kg). Major origin-related
differences (P < 0.0001) were observed in the AME of SBM. The average AME content
of US, ARG, BRA, and IND samples was 2,375, 2,227, 2,317, and 2,000 kcal/kg (as
fed basis), respectively. Total AA contents of US, ARG, BRA, and IND samples were
similar (P > 0.05) for 9 of the 17 amino acids. Major differences (P < 0.05 to P
< 0.001) due to origin were determined for the digestibility of all AA. The IND
samples had the lowest (P < 0.05) digestibility and no differences (P > 0.05)
between samples from other 3 origins. However, the digestible CP content of US
SBM was higher (P < 0.05) than those of ARG and IND, but similar (P > 0.05) to
that from BRA. The digestible CP contents of SBM from the US, ARG, BRA, and IND
were 40.0, 38.6, 39.8, and 36.7%, respectively. Digestible contents of
indispensable AA, in general, followed the same trend as that of digestible CP.
In conclusion, the present evaluation showed that major differences in nutritive
value do exist between SBM from different origins in terms of nutrient contents,
AME, and digestible AA. Overall, SBM originating from the US had better nutritive
value compared with those from ARG and IND, on the basis of AME and contents of
digestible CP and digestible AA.
PMID- 25125561
TI - Effects of alkaline concentration, temperature, and additives on the strength of
alkaline-induced egg white gel.
AB - Egg whites can undergo gelation at extreme pH. In this paper, the effects of NaOH
concentration (1.5, 2, 2.5, and 3%), temperature (10, 20, 30, and 40 degrees C),
and additives (metallic compounds, carbohydrates, stabilizers, and coagulants) on
the strength of alkaline-induced egg white gel were investigated. Results showed
that NaOH concentration and induced temperature significantly affected the rate
of formation and peak strength of the egg white gel. Of the 6 metallic compounds
used in this experiment, CuSO4exhibited the optimal effect on the strength of
alkaline-induced egg white gel, followed by MgCl2, ZnSO4, PbO, and CaCl2. When
CuSO4concentration was 0.2%, the gel strength increased by 31.92%. The effect of
Fe2(SO4)3was negligible. Of the 5 carbohydrate additives, xanthan gum (0.2%)
caused the highest increase (54.31%) in the strength of alkaline-induced egg
white gel, followed by sodium alginate, glucose, starch, and sucrose. Meanwhile,
propylene glycol (0.25%) caused the highest improvement (15.78%) in the strength
of alkaline-induced egg white gel among the 3 stabilizing agents and coagulants
used, followed by Na2HPO4and glucono-delta-lactone.
PMID- 25125562
TI - Neopterin and biopterin as biomarkers of immune system activity associated with
crating in broiler chickens.
AB - Neopterin and biopterin belong to a group of unconjugated pterin derivates. These
biomolecules are present in many animal species and perform several functions.
Pterin concentrations may provide additional information on the effect of stress
on immune system activity. This study focused on an investigation of the effect
of crating on plasma concentrations of neopterin and biopterin in broilers. The
effects of 2 crating periods (2 and 4 h) were monitored in Hubbard broilers (n =
90) aged 42 d. After a given crating period, randomly selected chickens from each
group were sampled immediately and the remaining chickens were sampled after 24
h. Plasma corticosterone increased (P < 0.001) immediately after 2 and 4 h
crating, but no difference between the crated and the control noncrated broilers
was found 24 h later. Immediately after crating, neopterin in 2- and 4-h broilers
did not differ from the control, but 24 h later a decrease (P = 0.011) in plasma
neopterin was found in 4-h broilers compared with the control. Simultaneously, 24
h after crating, neopterin levels in 2- and 4-h broilers decreased (P < 0.001) in
comparison with the levels immediately after crating. Plasma biopterin was higher
(P < 0.001) in 4-h broilers than in the control immediately after the crating. A
time of sampling effect (P = 0.016) was found for the heterophil-to-lymphocyte
ratio, with heterophil-to-lymphocyte ratio higher 24 h after crating in
comparison with its level immediately after the crating. This study shows that
crating may significantly affect the immune system of broiler chickens. This is
corroborated by the increase in plasma biopterin concentrations in broilers
immediately after crating and the decrease in plasma neopterin concentrations in
broilers 24 h after crating. The correlations were found for widely used
indicators of acute and chronic stress in birds [i.e., plasma corticosterone
concentrations (biopterin) and the heterophil-to-lymphocyte ratio (neopterin),
respectively].
PMID- 25125563
TI - Single nucleotide polymorphism variants within tva and tvb receptor genes in
Chinese chickens.
AB - Avian leukosis is an immunosuppressive neoplastic disease caused by avian
leukosis viruses (ALV), which causes tremendous economic losses in the worldwide
poultry industry. The susceptibility or resistance of chicken cells to subgroup A
ALV and subgroup B, D, and E ALV are determined by the receptor genes tumor virus
locus A (tva) and tumor virus locus B (tvb), respectively. Four genetic resistant
loci (tva(r1), tva(r2), tva(r3), and tva(r4)) in tva receptor gene and a genetic
resistant locus tvb(r) in the tvb receptor gene have been identified in inbred
lines of White Leghorn. To evaluate the genetic resistance to subgroup A, B, D,
and E ALV, genetic variations within resistant loci in tva and tvb genes were
screened in Chinese local chicken breeds and commercial broiler lines. Here, the
heterozygote tva(s1/r1) and the resistant genotype tva(r2/r2), tva(r3/r3), and
tva(r4/r4) were detected in Chinese chickens by direct sequencing. The
heterozygote tva(s1/r1) was detected in Huiyang Bearded chicken (HYBC), Rizhaoma
chicken, and commercial broiler line 13 to 15 (CB13 to CB15), with the
frequencies at 0.08, 0.18, 0.17, 0.25, and 0.15, respectively. The resistant
genotype tva(r2/r2) was detected in Jiningbairi chicken (JNBRC), HYBC, and CB15,
with the frequencies at 0.03, 0.08, and 0.06, respectively, whereas tva(r3/r3)
and tva(r4/r4) were detected in 19 and 17 of the 25 Chinese chickens tested, with
the average frequencies at 0.13 and 0.20, respectively. Furthermore, the
resistant genotype tvb(r/r) was detected in JNBRC, CB07, CB12, CB14, and CB15 by
pyrosequencing assay, with the frequencies at 0.03, 0.03, 0.11, 0.09, and 0.15,
respectively. These results demonstrated that the potential for genetic
improvement of resistance to subgroup A, B, D, and E ALV were great both in
Chinese local chickens and commercial broilers. This study provides valuable
insight into the selective breeding for chickens genetically resistant to ALV.
PMID- 25125564
TI - Urea cycle disorders: a life-threatening yet treatable cause of metabolic
encephalopathy in adults.
AB - Urea cycle disorders are inborn errors of metabolism that, in rare cases, can
present for the first time in adulthood. We report a perplexing presentation in a
woman 4 days postpartum of bizarre and out-of-character behaviour interspersed
with periods of complete normality. Without any focal neurological signs or
abnormality on initial investigations, the diagnosis became clear with the
finding of a significantly elevated plasma ammonia level, just as she began to
deteriorate rapidly. She improved following intravenous dextrose and lipid
emulsion, together with sodium benzoate, arginine and a protein-restricted diet.
She remains well 12 months later with no permanent sequelae. Whilst this is a
rare presentation of an uncommon disease, it is a treatable disorder and its
early diagnosis can prevent a fatal outcome.
PMID- 25125565
TI - HIV-1 clinical isolates with the E138A substitution in reverse transcriptase show
full susceptibility to emtricitabine and other nucleoside reverse transcriptase
inhibitors.
PMID- 25125567
TI - eComment. Experimental controversy regarding the role of adipose-derived stem
cells in surgical oncology.
PMID- 25125568
TI - eComment. Underestimated occurrence of mesenteric ischaemia after cardiac
surgery.
PMID- 25125570
TI - Sustained ventricular tachycardia and coved-type electrocardiogram in peripheral
leads: a particularly malignant phenotype of Brugada syndrome?
PMID- 25125571
TI - Endocardial left ventricular lead placement from the left subclavian vein
approach.
AB - AIMS: In up to 10-15% of cases, the traditional epicardial approach for left
ventricular (LV) lead placement is not feasible and surgical implantation is
considered the alternative. We present the implantation of a transseptal LV lead
through a left subclavian access. METHODS AND RESULTS: Through the left
subclavian vein access and using a system which includes a guiding catheter, a
puncture screw catheter and a puncture stylet, access to the LV was achieved and
the LV stimulation lead was successfully implanted. CONCLUSION: We describe the
implantation of a transseptal LV stimulation lead through a left subclavian
access.
PMID- 25125572
TI - Unsuitability of the epidemiological approach to bicycle transportation injuries
and traffic engineering problems.
AB - Bicyclists and transportation professionals would do better to decline advice
drawn from characteristically epidemiological studies. The faults of epidemiology
are both accidental (unpreparedness for the task) and essential (unsuitability of
the methods). Characteristically epidemiological methods are known to be error
prone, and when applied to bicycle transportation suffer from diversion bias,
inappropriately broad-brush categorisations, a focus on undifferentiated risk
rather than on danger, a bias towards unsafe behaviour, and an overly narrow
perspective. To the extent that there is a role for characteristically
epidemiological methods, it should be the same as anywhere else: as a preliminary
or adjunct to the scientific method, for which there is no substitute.
PMID- 25125573
TI - Signalling at tight junctions during epithelial differentiation and microbial
pathogenesis.
AB - Tight junctions are a component of the epithelial junctional complex, and they
form the paracellular diffusion barrier that enables epithelial cells to create
cellular sheets that separate compartments with different compositions. The
assembly and function of tight junctions are intimately linked to the actomyosin
cytoskeleton and, hence, are under the control of signalling mechanisms that
regulate cytoskeletal dynamics. Tight junctions not only receive signals that
guide their assembly and function, but transmit information to the cell interior
to regulate cell proliferation, migration and survival. As a crucial component of
the epithelial barrier, they are often targeted by pathogenic viruses and
bacteria, aiding infection and the development of disease. In this Commentary, we
review recent progress in the understanding of the molecular signalling
mechanisms that drive junction assembly and function, and the signalling
processes by which tight junctions regulate cell behaviour and survival. We also
discuss the way in which junctional components are exploited by pathogenic
viruses and bacteria, and how this might affect junctional signalling mechanisms.
PMID- 25125574
TI - Thinness in the era of obesity: trends in children and adolescents in The
Netherlands since 1980.
AB - BACKGROUND: Although children both at the upper and lower tail of the body mass
index (BMI) distribution are at greater health risk, relatively little is known
about the development of thinness prevalence rates in developed countries over
time. We studied trends in childhood thinness and assessed changes in the BMI
distribution since the onset of the obesity epidemic. METHODS: Growth data from
54 814 children aged 2-18 years of Dutch, Turkish and Moroccan origin living in
The Netherlands were used. Anthropometric measurements were performed during
nationwide cross-sectional growth studies in 1980 (only Dutch), 1997 and 2009.
Prevalence rates of thinness grades I, II and III were calculated according to
international cut-offs. BMI distributions for 1980, 1997 and 2009 were compared.
RESULTS: Since 1980, thinness (all grades combined) reduced significantly from
14.0% to 9.8% in children of Dutch origin, but the proportion of extremely thin
children (grade III) remained constant. Thinness in children of Moroccan origin
decreased significantly from 8.8% to 6.2% between 1997 and 2009. No significant
difference was observed in children of Turkish origin (5.4% in 1997 vs. 5.7% in
2009). Thinness occurred most often in children aged 2-5 years. There were no
differences between boys and girls. The BMI distribution widened since 1980,
mainly due to an upward shift of the upper centiles. CONCLUSION: Since the onset
of the obesity epidemic, prevalence rates of thinness decreased. However, we
found a small but persistent group of extremely thin children. More research is
needed to gain insight into their health status.
PMID- 25125575
TI - 'By failing to prepare you are preparing to fail': lessons from the 2009 H1N1
'swine flu' pandemic.
AB - BACKGROUND: Pandemic influenza has the potential to cause widespread death and
destruction. Communications with the public have a vital role in the prevention
of pandemic influenza by promoting the effective uptake of behaviours that can
delay the spread of infection. This study explored the development and
implementation of communications in the pandemic influenza outbreak of H1N1
('swine flu') in 2009 in three European countries. METHODS: In-depth interviews
were conducted with senior policy and communication officials involved in the
planning and delivery of communications programmes in England, Italy and Hungary.
RESULTS: The study found a lack of planning and a low value attached to the
skills required to produce effective communications. In all case study countries
there was a dearth of good quality audience research to inform the development of
communications. Little thought had been given to the tone, targeting or
channelling of messages. Instead, communications were characterized by a 'one
size fits all' and a 'top down', expert-led response. There was also little
effort to evaluate the impact of communications, but where this was done, very
low levels of public compliance and engagement with key behavioural messages were
found. CONCLUSIONS: Policy makers should prioritize investment in the skills and
expertise required to achieve desired behaviour changes. Audience research should
be conducted throughout the planning cycle to inform national communications
strategies. This should include insights to inform the segmentation of public
audiences, targeting of messages and consideration of content and emotional tone
most likely to achieve desired behavioural outcomes.
PMID- 25125576
TI - Mapping the denominator: spatial demography in the measurement of progress.
AB - Measuring progress towards international health goals requires a reliable
baseline from which to measure change and recent methodological advancements have
advanced our abilities to measure, model and map the prevalence of health issues
using sophisticated tools. The provision of burden estimates generally requires
linking these estimates with spatial demographic data, but for many resource-poor
countries data on total population sizes, distributions, compositions and
temporal trends are lacking, prompting a reliance on uncertain estimates. Modern
technologies and data archives are offering solutions, but the huge range of
uncertainties that exist today in spatial denominator datasets will still be
around for many years to come.
PMID- 25125577
TI - 'A living death': a qualitative assessment of quality of life among women with
trichiasis in rural Niger.
AB - BACKGROUND: Prior to blindness, trachoma is thought to profoundly affect women's
abilities to lead normal lives, but supporting evidence is lacking. To better
understand the effects of trichiasis, we asked women to define quality of life,
how trichiasis affects this idea and their perceptions of eyelid surgery.
METHODS: Operated and unoperated women were purposively selected for in-depth
interviews. These were audio-recorded and transcribed, and codes were identified
and applied to the transcripts. Overarching themes, commonalities and differences
were identified and matched to quotations. RESULTS: Twenty-three women were
interviewed. Quality of life was defined as health, security, family, social
status and religious participation. Trichiasis caused severe pain and loss of
health, leading to loss of security. This affected social, economic and religious
activities and caused burden on their families. Surgery improved quality of life,
even in cases of surgical failure or recurrent disease. CONCLUSIONS: Trichiasis
disables most women, even those reporting fewer or less-severe symptoms. While
women in rural Niger often live in extreme poverty, trichiasis exacerbates the
situation, making women unable to work and undermining their social status. It
adds to family burden, as women lose the ability to meaningfully contribute to
the household and require additional family resources for their care.
PMID- 25125578
TI - Factors associated with physical therapists' implementation of physical activity
interventions in The Netherlands.
AB - BACKGROUND: Physical therapists play an important role in the promotion of
physical activity (PA) and the effectiveness of PA interventions. However, little
is known about the extent to which they implement PA interventions following the
intervention protocol and about the factors influencing their implementation
behaviors. OBJECTIVE: The study objective was to investigate physical therapists'
implementation fidelity regarding PA interventions, including completeness and
quality of delivery, and influencing factors with a Theoretical Domains Framework
based questionnaire. DESIGN: The study was based on a cross-sectional design.
METHODS: A total of 268 physical therapists completed the Determinants of
Implementation Behavior Questionnaire. Questions about completeness and quality
of delivery were based on components and tasks of PA interventions as described
by the Royal Dutch Society for Physical Therapy. Multilevel regression analyses
were used to identify factors associated with completeness and quality of
delivery. RESULTS: High implementation fidelity was found for the physical
therapists, with higher scores for completeness of delivery than for quality of
delivery. Physical therapists' knowledge, skills, beliefs about capabilities and
consequences, positive emotions, behavioral regulation, and the automaticity of
PA intervention delivery were the most important predictors of implementation
fidelity. Together, the Theoretical Domains Framework accounted for 23% of the
variance in both total completeness and total quality scores. LIMITATIONS: The
cross-sectional design precluded the determination of causal relationships. Also,
the use of a self-report measure to assess implementation fidelity could have led
to socially desirable responses, possibly resulting in more favorable ratings for
completeness and quality. CONCLUSIONS: This study enhances the understanding of
how physical therapists implement PA interventions and which factors influence
their behaviors. Knowledge about these factors may assist in the development of
strategies to improve physical therapists' implementation behaviors.
PMID- 25125580
TI - Inhibition of TRPM8 channels reduces pain in the cold pressor test in humans.
AB - The transient receptor potential (subfamily M, member 8; TRPM8) is a nonselective
cation channel localized in primary sensory neurons, and is a candidate for cold
thermosensing, mediation of cold pain, and bladder overactivity. Studies with
TRPM8 knockout mice and selective TRPM8 channel blockers demonstrate a lack of
cold sensitivity and reduced cold pain in various rodent models. Furthermore,
TRPM8 blockers significantly lower body temperature. We have identified a
moderately potent (IC50 = 103 nM), selective TRPM8 antagonist, PF-05105679 [(R)-3
[(1-(4-fluorophenyl)ethyl)(quinolin-3-ylcarbonyl)amino]methylbenzoic acid]. It
demonstrated activity in vivo in the guinea pig bladder ice water and menthol
challenge tests with an IC50 of 200 nM and reduced core body temperature in the
rat (at concentrations >1219 nM). PF-05105679 was suitable for acute
administration to humans and was evaluated for effects on core body temperature
and experimentally induced cold pain, using the cold pressor test. Unbound plasma
concentrations greater than the IC50 were achieved with 600- and 900-mg doses.
The compound displayed a significant inhibition of pain in the cold pressor test,
with efficacy equivalent to oxycodone (20 mg) at 1.5 hours postdose. No effect on
core body temperature was observed. An unexpected adverse event (hot feeling) was
reported, predominantly periorally, in 23 and 36% of volunteers (600- and 900-mg
dose, respectively), which in two volunteers was nontolerable. In conclusion,
this study supports a role for TRPM8 in acute cold pain signaling at doses that
do not cause hypothermia.
PMID- 25125579
TI - Anaplerotic metabolism of alloreactive T cells provides a metabolic approach to
treat graft-versus-host disease.
AB - T-cell activation requires increased ATP and biosynthesis to support
proliferation and effector function. Most models of T-cell activation are based
on in vitro culture systems and posit that aerobic glycolysis is employed to meet
increased energetic and biosynthetic demands. By contrast, T cells activated in
vivo by alloantigens in graft-versus-host disease (GVHD) increase mitochondrial
oxygen consumption, fatty acid uptake, and oxidation, with small increases of
glucose uptake and aerobic glycolysis. Here we show that these differences are
not a consequence of alloactivation, because T cells activated in vitro either in
a mixed lymphocyte reaction to the same alloantigens used in vivo or with
agonistic anti-CD3/anti-CD28 antibodies increased aerobic glycolysis. Using
targeted metabolic (13)C tracer fate associations, we elucidated the metabolic
pathway(s) employed by alloreactive T cells in vivo that support this phenotype.
We find that glutamine (Gln)-dependent tricarboxylic acid cycle anaplerosis is
increased in alloreactive T cells and that Gln carbon contributes to ribose
biosynthesis. Pharmacological modulation of oxidative phosphorylation rapidly
reduces anaplerosis in alloreactive T cells and improves GVHD. On the basis of
these data, we propose a model of T-cell metabolism that is relevant to activated
lymphocytes in vivo, with implications for the discovery of new drugs for immune
disorders.
PMID- 25125581
TI - Commentary: Does mortality from smoking have implications for future Mendelian
randomization studies?
PMID- 25125582
TI - Auditing documentation on delivery room management using video and physiological
recordings.
AB - OBJECTIVE: Neonatal resuscitation is often retrospectively documented, which can
lead to inaccuracy and incomplete recording of delivery room management. In this
study, we assessed the accuracy and completeness of neonatal resuscitation
documentation in our neonatal intensive care unit. METHODS: Recordings of
physiological parameters and video data were performed in the delivery room and
used to deduct the clinical condition of the infant, the interventions done and
their effect on the infant's condition. The data from the recordings were
compared with the documentation on neonatal stabilisation in the medical records
(paper or digital). RESULTS: Recordings of 54 infants were compared with the
documentation in their medical records. In 93% of the medical records delivery
room management was documented. The clinical condition of the infant at birth was
documented in 76% and 1 min Apgar scores in 98%. Respiratory support was
correctly documented in 83%, heart rate in 37% and oxygen saturation in 13%. In
57% use of supplemental oxygen and its indication were correctly reported. Seven
infants were intubated and this was correctly documented in 57%. Apgar scores
were compared between the recordings and the medical records. At 1 min, 5 min and
10 min after birth the Apgar score, given by the researcher using the recordings,
was similar to the scores in the medical records in 33%, 44% and 53%,
respectively. CONCLUSIONS: Accurate and complete documentation of neonatal
resuscitation continues to be a challenge. Recordings of physiological parameters
and video imaging can improve documentation by providing detailed information.
PMID- 25125583
TI - Brain. Editorial.
PMID- 25125584
TI - 'Idiopathic' no more! Abnormal interaction of large-scale brain networks in
generalized epilepsy.
PMID- 25125585
TI - Hereditary dystonia and parkinsonism: two sides of the same coin?
PMID- 25125586
TI - Neuronal substrate of cognitive impairment in post-stroke dementia.
PMID- 25125587
TI - The next step in modern brain lesion analysis: multivariate pattern analysis.
PMID- 25125588
TI - Psoriatic arthritis: current therapy and future approaches.
AB - PsA is a systemic inflammatory condition that affects 20-30% of patients with
psoriasis. It is characterized by potential involvement of diverse tissues,
including peripheral and axial joints, enthesitis, dactylitis and skin and nail
disease. The degree of involvement in each domain can vary over time in
individual patients and can differ substantially between PsA patients. The
clinical heterogeneity along with the varying extent of severity and activity can
pose significant challenges to treatment. Although some studies had suggested
immunopathophysiological similarities between PsA and RA, more recently important
distinctions have been defined. Similarly, although some immunomodulatory
therapies have proved effective for both PsA and RA, recent data suggest distinct
responses to certain targeted therapies. Herein, current DMARDs and biologic
agents as well as the potential role of emerging therapeutics will be reviewed.
PMID- 25125589
TI - Impact of musculoskeletal pain on insomnia onset: a prospective cohort study.
AB - OBJECTIVE: Pain, the most common manifestation of rheumatological conditions, is
highly prevalent among older adults, with worse health outcomes found in those
with co-morbid insomnia. Proactive prevention of insomnia may reduce the overall
disease burden of pain and rheumatological conditions. To inform such
development, this study examined the role of pain, physical limitation and
reduced social participation in predicting and mediating insomnia onset. METHODS:
A prospective cohort study was conducted involving 6676 individuals >=50 years of
age who completed questionnaires at baseline and a 3-year follow-up. Participants
were classified into none, some and widespread pain according to the ACR
criteria. Logistic regression was used to examine the relationship between
baseline pain and insomnia onset at 3 years. Path analysis was used to test for
the mediating role of physical limitation and social participation restriction.
RESULTS: Some [adjusted odds ratio (AOR) 1.57 (95% CI 1.15, 2.13)] and widespread
[2.13 (1.66, 3.20)] pain increased the risk of insomnia onset at 3 years, after
adjusting for age, gender, socio-economic class, education, anxiety, depression,
sleep and co-morbidity at baseline. The combination of physical limitation and
reduced social participation explained up to 68% of the effect of some pain on
insomnia onset and 66% of the effect of widespread pain on insomnia onset.
CONCLUSION: There was a dose-response association between the extent of pain at
baseline and insomnia onset at 3 years that was substantially mediated by
physical limitation and reduced social participation. Targeting physical
limitation and social participation in older people with pain may buffer co
morbid insomnia, reducing the overall disease burden.
PMID- 25125590
TI - Comparison between three systems of classification criteria in juvenile systemic
lupus erythematous.
AB - OBJECTIVE: The most widely used classification criteria for SLE are those derived
and validated in adult patients by the ACR. Alternatives include the Boston
weighted (BW) and SLICC criteria. The aim of this study was to compare the
performance of BW and SLICC criteria with the 1997 ACR criteria in a JSLE cohort.
METHODS: Cases were JSLE patients and controls were patients with other rheumatic
diseases attending a tertiary centre in the past 10 years. Data were
retrospectively collected to establish the ACR, BW and SLICC criteria fulfilled
at the first visit and within the first year of follow-up. A consensus diagnosis
of JSLE established by the same group of highly experienced paediatric
rheumatologists was chosen as the standard of reference. RESULTS: One hundred and
seventy-three patients were included: 81 JSLE and 92 controls. There was a sharp
increase in sensitivity and prevalence of all criteria within the first year of
follow-up. The BW criteria had higher sensitivity than the ACR criteria (81.5% vs
58%, P < 0.001) at the first visit, but lower specificity in both periods. SLICC
criteria had higher sensitivity (82.7% vs 58%, P < 0.001) at the first visit, but
similar specificity in both periods. CONCLUSION: In this JSLE population, the
SLICC criteria performed best in terms of sensitivity and accuracy at the first
visit and within the first year of follow-up.
PMID- 25125591
TI - Factors influencing work disability in psoriatic arthritis: first results from a
large UK multicentre study.
AB - OBJECTIVE: The aim of this study was to determine the extent to which structural
damage, clinical disease activity, demographic and social factors are associated
with work disability (WD) in PsA. METHODS: Four hundred patients fulfilling
CASPAR (Classification Criteria for Psoriatic Arthritis) criteria for PsA were
recruited from 23 hospitals across the UK. Demographic, socio-economic, work,
clinical and radiographic data were collected. WD was assessed with the Work
Productivity and Activity Impairment Specific Health Problem (WPAI-SHP)
questionnaire reporting WD as a percentage of absenteeism (work time missed),
presenteeism (impairment at work/reduced effectiveness) and work productivity
loss (overall work impairment/absenteeism plus presenteeism). Logistic and linear
regressions were conducted to investigate associations with WD. RESULTS: Two
hundred and thirty-six participants of any age were in work. Absenteeism,
presenteeism and productivity loss rates were 14% (s.d. 29.0), 39% (s.d. 27.2)
and 46% (s.d. 30.4), respectively. Ninety-two (26%) participants of working age
were unemployed. Greater age, disease duration of 2-5 years and worse physical
function were associated with unemployment. Patients reported that employer
awareness and helpfulness exerted a strongly positive influence on remaining in
employment. Higher levels of global and joint-specific disease activity and worse
physical function were associated with greater levels of presenteeism and
productivity loss among those who remained in work. CONCLUSION: Reduced
effectiveness at work was associated with measures of disease activity, whereas
unemployment, considered the endpoint of WD, was associated with employer
factors, age and disease duration. A longitudinal study is under way to determine
whether treatment to reduce disease activity ameliorates WD in the real-world
setting.
PMID- 25125592
TI - Interferon gene expression signature in rheumatoid arthritis neutrophils
correlates with a good response to TNFi therapy.
AB - OBJECTIVE: The aim of this study was to use whole transcriptome sequencing (RNA
Seq) of RA neutrophils to identify pre-therapy gene expression signatures that
correlate with disease activity or response to TNF inhibitor (TNFi) therapy.
METHODS: Neutrophils were isolated from the venous blood of RA patients (n = 20)
pre-TNFi therapy and from healthy controls (n = 6). RNA was poly(A) selected and
sequenced on the Illumina HiSeq 2000 platform. Reads were mapped to the human
genome (hg19) using TopHat and differential expression analysis was carried out
using edgeR (5% false discovery rate). Signalling pathway analysis was carried
out using Ingenuity Pathway Analysis (IPA) software. IFN signalling was confirmed
by western blotting for phosphorylated signal transducer and activator of
transcription (STAT) proteins. Response to TNFi was measured at 12 weeks using
change in the 28-item DAS (DAS28). RESULTS: Pathway analysis with IPA predicted
activation of IFN signalling in RA neutrophils, identifying 178 IFN-response
genes regulated by IFN-alpha, IFN-beta or IFN-gamma (P < 0.01). IPA also
predicted activation of STAT1, STAT2 and STAT3 transcription factors in RA
neutrophils (P < 0.01), which was confirmed by western blotting. Expression of
IFN-response genes was heterogeneous and patients could be categorized as IFN
high or IFN-low. Patients in the IFN-high group achieved a better response to
TNFi therapy [DeltaDAS28, P = 0.05, odds ratio (OR) 1.4 (95% CI 1.005, 1.950)]
than patients in the IFN-low group. The level of expression of IFN-response genes
(IFN score) predicted a good response [European League Against Rheumatism (EULAR)
criteria] to TNFi using receiver operating characteristic curve analysis (area
under the curve 0.76). CONCLUSION: IFN-response genes are significantly up
regulated in RA neutrophils compared with healthy controls. Higher IFN-response
gene expression in RA neutrophils correlates with a good response to TNFi
therapy.
PMID- 25125593
TI - Tumour necrosis factor inhibitor therapy and infection risk in axial
spondyloarthritis: results from a longitudinal observational cohort.
AB - OBJECTIVES: Long-term data on infection risk in axial SpA (axSpA) are sparse. TNF
inhibitors (TNFis) are increasingly being used in axSpA, with infection being the
most important adverse event. We aimed to investigate the frequency of infections
in axSpA and to identify factors predisposing to infection. METHODS: Data were
extracted from a longitudinal observational cohort of patients with axSpA.
Infection rates were calculated and multivariate analysis was performed to
investigate the association of independent variables with infection. RESULTS:
Data were analysed for 440 patients followed for a total of 1712 patient-years
(pys). A total of 259 infections, of which 23 were serious, were recorded in 185
patients. The overall rate of any infection was 15 (95% CI 13, 17)/100 pys and
the serious infection rate was 1.3 (95% CI 0.9, 2.0)/100 pys. There was no
significant difference in the rate of any infection or serious infection in
patients on TNFis compared with patients never on biologic agents. In the
multivariate analysis, DMARD treatment, but not TNFi treatment, was associated
with risk of infection. Age, disease duration, smoking status, BASFI, BASDAI, co
morbidity score and hospitalization were not associated with an increased risk of
infection. CONCLUSION: The serious infection rate in axSpA in this observational
cohort is low when compared with rates reported in other rheumatic diseases.
Biologic use was not a significant risk factor for serious infection.
PMID- 25125596
TI - In situ exposure assessment of intermediate frequency fields of diverse devices.
AB - In this study, in situ exposure assessment of both electric and magnetic fields
of different intermediate frequency (IF) sources is investigated. The authors
investigated smart boards and touchscreens, energy-saving bulbs, fluorescent
lamps, a portable hearing unit and an electrosurgical unit (ESU). For most of
these sources, the electric field is the dominating quantity. International
Commission on Non-Ionizing Radiation Protection reference levels are exceeded for
touchscreens (44 kHz: up to 155.7 V m(-1) at 5 cm), energy-saving bulbs (38-52
kHz: up to 117.3 V m(-1)), fluorescent lamps (52 kHz: up to 471 V m(-1) at 5 cm)
and ESUs (up to 920 kHz: 792 V m(-1) at 0.5 cm). Magnetic field strengths up to
1.8 and 10.5 A m(-1) were measured close to the ESU and portable hearing unit (69
V m(-1)), respectively. Large differences of measured field values exist among
the various operating modes of the IF equipment. Compliance distances for general
public range from 15.3 cm (touchscreen) to 25 cm (fluorescent lamps).
PMID- 25125594
TI - Twenty-two points to consider for clinical trials in systemic sclerosis, based on
EULAR standards.
AB - OBJECTIVE: SSc is clinically and aetiopathogenically heterogeneous. Consensus
standards for more uniform trial design and selection of outcome measures are
needed. The objective of this study was to develop evidence-based points to
consider (PTCs) for future clinical trials in SSc. METHODS: Thirteen
international SSc experts experienced in SSc clinical trial design were invited
to participate. One researcher with experience in systematic literature review
and three trainees were also included. A systematic review using PubMed and the
Cochrane Central Register of Controlled Trials was conducted and PTCs when
designing clinical trials in SSc were developed. As part of that development we
conducted an Internet-based Delphi exercise regarding the main points to be made
in the consensus statement. Consensus was defined as achieving a median score of
>=7 of 9. RESULTS: By consensus, the experts decided to develop PTCs for each
individual organ system. The current document provides a unifying outline on PTCs
regarding general trial design, inclusion/exclusion criteria and analysis.
Consensus was achieved regarding all the main points of the PTCs. CONCLUSION:
Using European League Against Rheumatism suggestions for PTCs, a general outline
for PTCs for controlled clinical trials in SSc was developed. Specific outlines
for individual organ systems are to be published separately. This general outline
should lead to more uniform and higher-quality trials and clearly delineate areas
where further research is needed.
PMID- 25125597
TI - Effects of pupil center shift on ocular aberrations.
AB - PURPOSE: We investigated effects of pupil shifts, occurring with changes in
luminance and accommodation stimuli, on refraction components and higher-order
aberrations. METHODS: Participants were young and older groups (n = 20; 22 +/- 2
years; age range, 18-25 years; and n = 19, 49 +/- 4 years, 45-58 years,
respectively). Aberrations/refractions at 4- and 3-mm diameters were compared
between centered and decentered pupils for low (background, 0.01 cd/m(2), 0
diopters [D]), and high (6100 cd/m(2), 4 or 6 D) stimuli. Decentration was the
difference between pupil centers for low and high stimuli. Clinical important
changes with decentration were: M at +/- 0.50 or +/- 0.25 D, J180 and J45 at +/-
0.25 or +/- 0.125 D, HORMS at +/- 0.05 MUm, C(3, 1) at +/- 0.05 MUm, and C(4, 0)
at +/- 0.05 MUm. RESULTS: Because of small pupil shifts in most participants
(mean 0.26 mm), there were few important changes in most refraction components
and higher-order aberration terms. However, M changed by >0.25 D for a third of
participants with 4-mm pupils. When determining refractions from second to sixth
order aberration coefficients, the more stringent criteria gave 76/534 (14%)
possible important changes. Some participants had large pupil shifts with
considerable aberration changes. Comparisons at the high stimulus were possible
for only 11 participants because of small pupils. When refractions were
determined from second order aberration coefficients only, only 35 (7%) had
important changes for the more stringent criteria. CONCLUSIONS: Usually pupil
shifts with changes in stimulus conditions have little influence on aberrations,
but they can with high shifts. The number of aberrations orders that are
considered as contributing to refraction influences the proportion of cases that
might be considered clinically important.
PMID- 25125595
TI - A cluster of methylations in the domain IV of 25S rRNA is required for ribosome
stability.
AB - In all three domains of life ribosomal RNAs are extensively modified at
functionally important sites of the ribosome. These modifications are believed to
fine-tune the ribosome structure for optimal translation. However, the precise
mechanistic effect of modifications on ribosome function remains largely unknown.
Here we show that a cluster of methylated nucleotides in domain IV of 25S rRNA is
critical for integrity of the large ribosomal subunit. We identified the elusive
cytosine-5 methyltransferase for C2278 in yeast as Rcm1 and found that a combined
loss of cytosine-5 methylation at C2278 and ribose methylation at G2288 caused
dramatic ribosome instability, resulting in loss of 60S ribosomal subunits.
Structural and biochemical analyses revealed that this instability was caused by
changes in the structure of 25S rRNA and a consequent loss of multiple ribosomal
proteins from the large ribosomal subunit. Our data demonstrate that individual
RNA modifications can strongly affect structure of large ribonucleoprotein
complexes.
PMID- 25125598
TI - The combined effect of azithromycin and insulin-like growth factor-1 on cultured
human meibomian gland epithelial cells.
AB - PURPOSE: Meibomian gland dysfunction (MGD) is the leading cause of dry eye
disease, a prevalent disorder severely affecting patients' quality of life but
has no cure. We have discovered that azithromycin, a topical antibiotic used off
label to treat MGD-associated posterior blepharitis, directly acts on the human
meibomian gland epithelial cells (HMGECs) to promote their differentiation, and
in doing so, reduces cell proliferation. We have also found that insulin-like
growth factor-1 (IGF-1), a drug approved by the Food and Drug Administration
primarily used to treat dwarfism, stimulates the proliferation and lipid
accumulation in these cells. We hypothesize that the combination of azithromycin
and IGF-1 will promote cellular differentiation and lipid accumulation, while
preserving the normal proliferation of HMGECs. METHODS: We cultured immortalized
HMGECs with vehicle, 10 nM IGF-1, 10 MUg/mL azithromycin, or a combination of IGF
1 and azithromycin for 5 to 13 days. Cells were evaluated for intracellular
neutral lipids and lysosome accumulation by different staining methods; lipid
composition of cell lysates were analyzed using high-performance thin-layer
chromatography; proteins of interest (sterol regulatory element binding protein-1
[SREBP-1], cyclins B1 and D1) were measured by immunoblotting, and cell numbers
were counted using a hemocytometer. RESULTS: Our findings demonstrate that the
combination of azithromycin and IGF-1 promotes the differentiation and lipid
accumulation of HMGECs, while preserving their normal proliferation rate. This
combined treatment also increased the levels of neutral lipids, phospholipids,
and SREBP-1, and restored cyclin B1 content to control amounts. CONCLUSIONS: Our
results support our hypothesis, and this combination regime may represent a
unique and effective treatment of MGD.
PMID- 25125599
TI - Long-term therapeutic effects of mesenchymal stem cells compared to dexamethasone
on recurrent experimental autoimmune uveitis of rats.
AB - PURPOSE: We tested the long-term effects of different regimens of mesenchymal
stem cell (MSC) administration in a recurrent experimental autoimmune uveitis
(rEAU) model in rats, and compared the efficacy of MSC to that of dexamethasone
(DEX). METHODS: One or two courses of MSC treatments were applied to R16-specific
T cell-induced rEAU rats before or after disease onsets. The DEX injections were
given for 7 or 50 days continuously after disease onsets. Clinical appearances
were observed until the 50th day after transfer. On the 10th day, T cells from
control and MSC groups were analyzed by flow cytometry. Supernatants from the
proliferation assay and aqueous humor were collected for cytokine detection.
Functions of T cells and APCs in spleens also were studied by lymphocyte
proliferation assays. RESULTS: One course of MSC therapy, administered after
disease onset, led to a lasting therapeutic effect, with a decreased incidence,
reduced mean clinical score, and reduced retinal impairment after 50 days of
observation, while multiple courses of treatment did not improve the therapeutic
benefit. Although DEX and MSCs equally reduced the severity of the first episode
of rEAU, the effect of DEX was shorter lasting, and DEX therapy failed to control
the disease even with long periods of treatment. The MSCs significantly decreased
T helper 1 (Th1) and Th17 responses, suppressed the function of antigen
presenting cells, and upregulated T regulatory cells. CONCLUSIONS: These results
suggested that MSCs might be new corticosteroid spring agents, while providing
fewer side effects and longer lasting suppressive effects for recurrent uveitis.
PMID- 25125600
TI - Transgenic mice expressing mutated Tyr437His human myocilin develop progressive
loss of retinal ganglion cell electrical responsiveness and axonopathy with
normal iop.
AB - PURPOSE: To characterize age-related changes of retinal ganglion cell (RGC)
function, IOP, and anatomical markers of axon/glia integrity in a transgenic
mouse expressing Tyr437His mutant of human myocilin protein. METHODS: Retinal
ganglion cell electrical responsiveness was tested with pattern electroretinogram
(PERG) in 11 transgenic mice expressing mutated myocilin at different ages over
18 months under ketamine/xylazine anesthesia. Twelve age-matched C57BL/6J mice
also were tested as controls. Intraocular pressure was measured with a Tonolab
tonometer. Immunohistochemistry for GFAP and neurofilament was performed on
dissected optic nerve heads. RESULTS: In transgenic mice expressing mutated
myocilin, the PERG amplitude progressively decreased with increasing age by
approximately 50%, whereas the PERG peak latency increased by approximately 40 ms
(ANOVA, P < 0.05). In contrast, PERGs of young and old control mice had similar
amplitudes and peak latencies. In transgenic mice, GFAP staining was more intense
and extended than in control mice, and increased with increasing age;
neurofilament staining showed swollen and partially degenerated axons in old
transgenic mice. The IOP of young transgenic mice was similar to that of control
mice and did not significantly change with increasing age. CONCLUSIONS:
Transgenic mice expressing mutated human myocilin display progressive age-related
changes in RGC electrical responsiveness that are not associated with IOP
elevation but are associated with marked astrogliosis and axonopathy. Our results
support the view that MYOC expression in the optic nerve may impact structural,
metabolic, or neurotrophic support to RGC axons, thereby influencing their
susceptibility to glaucomatous damage independently of IOP.
PMID- 25125601
TI - Pseudomonas aeruginosa infectious keratitis in a high oxygen transmissible rigid
contact lens rabbit model.
AB - PURPOSE: To establish a rabbit model of infectious Pseudomonas aeruginosa
keratitis using ultrahigh oxygen transmissible rigid lenses and characterize the
frequency and severity of infection when compared to a non-oxygen transmissible
lens material. METHODS: Rabbits were fit with rigid lenses composed of ultrahigh
and non-oxygen transmissible materials. Prior to wear, lenses were inoculated
with an invasive corneal isolate of P. aeruginosa stably conjugated to green
fluorescent protein (GFP). Corneas were examined before and after lens wear using
a modified Heidelberg Rostock Tomograph in vivo confocal microscope. Viable
bacteria adherent to unworn and worn lenses were assessed by standard plate
counts. The presence of P. aeruginosa-GFP and myeloperoxidase-labeled neutrophils
in infected corneal tissue was evaluated using laser scanning confocal
microscopy. RESULTS: The frequency and severity of infectious keratitis was
significantly greater with inoculated ultrahigh oxygen transmissible lenses.
Infection severity was associated with increasing neutrophil infiltration and in
severe cases, corneal melting. In vivo confocal microscopic analysis of control
corneas following lens wear confirmed that hypoxic lens wear was associated with
mechanical surface damage, whereas no ocular surface damage was evident in the
high-oxygen lens group. CONCLUSIONS: These data indicate that in the absence of
adequate tear clearance, the presence of P. aeruginosa trapped under the lens
overrides the protective effects of oxygen on surface epithelial cells. These
findings also suggest that alternative pathophysiological mechanisms exist
whereby changes under the lens in the absence of frank hypoxic damage result in
P. aeruginosa infection in the otherwise healthy corneal epithelium.
PMID- 25125602
TI - Constitutive and LPS-induced expression of MCP-1 and IL-8 by human uveal
melanocytes in vitro and relevant signal pathways.
AB - PURPOSE: Melanocytes are one of the major cellular components in the uvea.
Interleukin-8/CXCL8 and monocyte chemoattractant protein-1 (MCP-1/CCL2) are the
two most important proinflammatory chemokines. We studied the constitutive and
lipopolysaccharide (LPS)-induced expression of IL-8 and MCP-1 in cultured human
uveal melanocytes (UM) and explored the relevant signal pathways. METHODS:
Conditioned media and cells were collected from UM cultured in medium with and
without stimulation of LPS. Interleukin-8 and MCP-1 proteins and mRNAs were
measured using an ELISA kit and RT-PCR, respectively. Nuclear factor (NF)-kappaB
in nuclear extracts and phosphorylated p38 mitogen-activated protein kinase
(MAPK), extracellular signal-regulated kinases1/2 (ERK1/2), and c-Jun N-terminal
kinase1/2 (JNK1/2) in cells cultured with and without LPS were measured by ELISA
kits. Inhibitors of p38 (SB203580), ERK1/2 (UO1026), JNK1/2 (SP600125), and NF
kappaB (BAY11-7082) were added to the cultures to evaluate their effects.
RESULTS: Low levels of IL-8 and MCP-1 proteins were detected in the conditioned
media in UM cultured without serum. Lipopolysaccharide (0.01-1 MUg/mL) increased
IL-8 and MCP-1 mRNAs and proteins levels in a dose- and time-dependent manner,
accompanied by a significant increase of phosphorylated JNK1/2 in cell lysates
and NF-kappaB in nuclear extracts. Nuclear factor-kappaB and JNK1/2 inhibitors
significantly blocked LPS-induced expression of IL-8 and MCP-1. CONCLUSIONS: This
is the first report on the expression and secretion of chemokines by UM. The data
suggest that UM may play a role in the pathogenesis of ocular inflammatory
diseases.
PMID- 25125604
TI - The staining pattern of brilliant blue G during macular hole surgery: a
clinicopathologic study.
AB - PURPOSE: To describe the intraoperative staining pattern of the internal limiting
membrane (ILM)-specific dye Brilliant Blue G (BBG) in a cohort of patients with
idiopathic macular holes; to analyze the associations of the staining pattern
with pre- and postoperative variables and to correlate the staining pattern with
transmission electron microscopy (TEM) of the excised ILM. METHODS: Fifty-five
consecutive patients were studied. The staining pattern was divided into three
subtypes based on the intraoperative appearance. The presence of a narrow rim of
nonstaining around the macular hole (MH) edge was noted and measured. In the
final 21 patients, the excised ILM was examined with TEM. RESULTS: The pattern of
staining observed was categorized as uniform in 33 patients (60%), patchy
nonstaining in 17 (31%), and no visible staining in 5 (9%). The staining pattern
correlated with the MH stage. In the patients with uniform or patchy staining, a
nonstaining rim was observed in 26 (52%) of the 50. The presence of a rim was
associated with a greater hole diameter and lower postoperative visual acuity.
The stain pattern correlated significantly with the amount of cellular tissue on
the vitreous side of the ILM on TEM, with a greater proportion of multicellular
layer membranes and new collagen in the incomplete staining groups. CONCLUSIONS:
A variety of nonstaining patterns around macular holes can be observed using BBG,
and these patterns correlate to the amount of cellular tissue on the vitreous
side of the ILM seen histologically. These patterns could be used to guide the
ILM peeling requirement or extent in future studies.
PMID- 25125603
TI - Sunlight exposure, pigmentation, and incident age-related macular degeneration.
AB - PURPOSE: Examine potential effects of sunlight exposure, hair color, eye color,
and selected gene single-nucleotide polymorphisms (SNPs) on incidence of AMD.
METHODS: Subjects participated in up to five examinations over a 20-year period.
Eye color, self-reported hair color as a teenager, and sunlight exposure were
ascertained at the baseline examination. Presence and severity of AMD and its
lesions were determined via fundus photographs. Genetic data were available on a
subset of participants. The SNPs CFH Y402H rs1061170 and ARMS2 A69S rs10490924
were used to analyze genetic risk of AMD; OCA2 rs4778241 and HERC2 rs12913832
represented genetic determinants of eye color. RESULTS: Incidence of early AMD
was higher in blond/red-haired persons compared with brown/black-haired persons
(hazard ratio [HR] 1.25, P = 0.02) and in persons with high sun exposure in their
thirties (HR 1.41, P = 0.02). However, neither was significant after adjustment
for multiple comparisons. Eye (HR 1.36, P = 0.006) and hair color (HR 1.42, P =
0.003) were associated with incidence of any retinal pigmentary abnormalities
(RPAs). Both remained significant after adjustment for multiple comparisons.
Neither presence of alleles for light-colored eyes nor those associated with high
risk of late AMD altered the association of eye or hair color with early AMD.
None of the characteristics studied were significantly associated with late AMD.
CONCLUSIONS: Modest associations of eye color, hair color, and HERC2 genotype
with any RPAs were found. Genes for AMD did not affect these associations. Eye
color phenotype was more strongly associated with outcomes than HERC2 or OCA2
genotype.
PMID- 25125605
TI - Comparative transcriptomic analysis of cultivated limbal epithelium and donor
corneal tissue reveals altered wound healing gene expression.
AB - PURPOSE: The improved surgical outcomes associated with transplantation of
cultivated amniotic membrane expanded limbal epithelium (AMLE) compared to
traditional donor methods has led to substantial adoption of this technique for
treatment of limbal stem cell deficiency. METHODS: The mRNA expression profiles
of AMLE and CE were assayed using microarrays. Transcripts with a 1.5-fold change
in either direction in addition to a Bonferroni adjusted P value < 0.05 were
considered to be differentially expressed. Expression changes detected by
microarray profiling and important corneal-limbal markers were assessed using
quantitative real-time PCR (qRT-PCR) and immunofluorescence staining. RESULTS: A
total of 487 probe sets (319 upregulated and 168 downregulated) were found to be
differentially expressed between AMLE and CE. Enrichment analysis revealed
significant overrepresentation of multiple biological processes (e.g., response
to wounding, wound healing, and regulation of cell morphogenesis) within the
differentially expressed gene list. The expression of a number of genes that were
upregulated (ABCG2, S100A9, ITGA5, TIMP2, FGF5, PDGFC, SEMA3A) and downregulated
(KLF4, P63alpha) in AMLE was confirmed using qRT-PCR. Immunofluorescence
confirmed that AMLE cultures were P63alpha, ABCG2, CK3, CK12, and E-cadherin (E
cad) positive. CONCLUSIONS: In this study, we have shown that genes associated
with wound healing processes are upregulated in AMLE. These gene expression
changes may contribute to corneal restoration and the positive outcomes
associated with transplantation.
PMID- 25125606
TI - Wnt and extraocular muscle sparing in amyotrophic lateral sclerosis.
AB - PURPOSE: The extraocular muscles (EOM) and their motor neurons are spared in
amyotrophic lateral sclerosis (ALS). In limb muscle, axon retraction from the
neuromuscular junctions occurs early in the disease. Wnts, a conserved family of
secreted signaling molecules, play a critical role in neuromuscular junction
formation. This is the first study to examine Wnt signaling for its potential
involvement in maintenance of normal morphology in EOM in ALS. METHODS:
Extraocular muscle and limb muscle axons, neuromuscular junctions, and myofibers
from control, aging, and ALS subjects and the SOD1(G93A) mouse model of ALS were
quantified for their expression of Wnt1, Wnt3a, Wnt5a, Wnt7a, and beta-catenin.
RESULTS: All four Wnt isoforms were expressed in most axon profiles in all human
EOM. Significantly fewer were positive for Wnt1, Wnt3a, and Wnt7a in the human
limb muscles. Similar differential patterns in Wnt myofiber expression were also
seen except in the case of Wnt7a, where expression was elevated. In the
SOD1(G93A) mouse, all four Wnt isoforms were significantly decreased in the
neuromuscular junctions at the terminal stage compared to values in age-matched
controls. beta-Catenin was activated in a subset of myofibers in EOM and limb
muscle in all subjects. CONCLUSIONS: The differences in expression of Wnts in EOM
and limb muscle, particularly at the neuromuscular junction level, suggest that
they play a role in the pathophysiology of ALS. Collectively, the data support a
role for signaling of Wnts in the preservation of the EOM in ALS and their
dysregulation and the subsequent development of pathology in the ALS limb
muscles.
PMID- 25125608
TI - Association between blood cadmium level and age-related macular degeneration in a
representative Korean population.
AB - PURPOSE: To investigate the association between blood cadmium level and AMD.
METHODS: This population-based, cross-sectional study using a nationwide,
systemically stratified, multistage, clustered sampling method included 4933
subjects older than 40 years who participated in the Korean National Health and
Nutrition Examination Survey (KNHANES) between 2008 and 2012 and had fundus
photographs taken. All participants underwent a standardized interview,
evaluation of blood cadmium concentrations, and comprehensive ophthalmic
examination. A 45 degrees digital fundus photograph was taken from both eyes
under physiologic mydriasis, and were graded using the international
classification and grading system for AMD. RESULTS: Mean blood cadmium levels
were 1.47 MUg/L in women and 1.19 MUg/L in men. After adjusting for potential
confounders, including age, sex, and smoking status, the odds ratio (OR) for AMD
was significantly increased in the highest quintile blood cadmium group (OR,
1.96; 95% confidence interval [CI], 1.17-3.29; P for trend = 0.017). This
association between blood cadmium level and AMD was significant in men (OR, 2.11;
95% CI, 1.11-4.02; P for trend = 0.024), but not in women (OR, 1.29; 95% CI, 0.70
2.52; P for trend = 0.158). CONCLUSIONS: This study provides the first
epidemiologic evidence that higher blood cadmium level is associated with AMD.
Results of the present study indicate that an elevated cadmium burden may
increase the risk of AMD development.
PMID- 25125607
TI - Loss of Raf-1 kinase inhibitory protein delays early-onset severe retinal
ciliopathy in Cep290rd16 mouse.
AB - PURPOSE: Mutations in the cilia-centrosomal protein of centrosomal protein of 290
kDa (CEP290) result in severe ciliopathies, including autosomal recessive early
onset childhood blindness disorder Leber congenital amaurosis (LCA). The
Cep290(rd16) (retinal degeneration 16) mouse model of CEP290-LCA exhibits
accumulation of CEP290-interacting protein Raf-1 kinase inhibitory protein (RKIP)
prior to onset of retinal degeneration (by postnatal day P14). We hypothesized
that reducing RKIP levels in the Cep290(rd16) mouse will delay or improve retinal
phenotype. METHODS: We generated double mutant mice by combining the Cep290(rd16)
and Rkip(ko) alleles (Cep290(rd16):Rkip(+/ko) and Cep290(rd16):Rkip(ko/ko)).
Retinal function was assessed by ERG and retinal morphology and protein
trafficking were assessed by histology, transmission electron microscopy (TEM),
and immunofluorescence analysis. Cell death was examined by apoptosis. RESULTS:
Prior to testing our hypothesis, we examined ERG and retinal morphology of
Rkip(ko/ko) mice and did not find any detectable differences compared with wild
type mice. The Cep290(rd16):Rkip(+/ko) mice exhibited similar retinopathy as
Cep290(rd16); however, Cep290(rd16): Rkip(ko/ko) double knockout mice
demonstrated a substantial improvement (>9-fold) in photoreceptor function and
structure at P18 as of Cep290(rd16) mice. We consistently detected transient
preservation of photoreceptors at P18 and polarized trafficking of opsins to
sensory cilia in the double mutant mice; however, retinal degeneration ensued by
P30. CONCLUSIONS: Our studies implicate CEP290-RKIP pathway in CEP290-retinal
degeneration and suggest that targeting RKIP levels can delay photoreceptor
degeneration, assisting in extending the time-window for treating such rapidly
progressing blindness disorder.
PMID- 25125609
TI - A novel mutation in VCP causes Charcot-Marie-Tooth Type 2 disease.
AB - Mutations in VCP have been reported to account for a spectrum of phenotypes that
include inclusion body myopathy with Paget's disease of the bone and
frontotemporal dementia, hereditary spastic paraplegia, and 1-2% of familial
amyotrophic lateral sclerosis. We identified a novel VCP mutation (p.Glu185Lys)
segregating in an autosomal dominant Charcot-Marie-Tooth disease type 2 family.
Functional studies showed that the Glu185Lys variant impaired autophagic function
leading to the accumulation of immature autophagosomes. VCP mutations should thus
be considered for genetically undefined Charcot-Marie-Tooth disease type 2.
PMID- 25125610
TI - Neuroanatomical precursors of dyslexia identified from pre-reading through to age
11.
AB - Developmental dyslexia is a common reading disorder that negatively impacts an
individual's ability to achieve literacy. Although the brain network involved in
reading and its dysfunction in dyslexia has been well studied, it is unknown
whether dyslexia is caused by structural abnormalities in the reading network
itself or in the lower-level networks that provide input to the reading network.
In this study, we acquired structural magnetic resonance imaging scans
longitudinally from 27 Norwegian children from before formal literacy training
began until after dyslexia was diagnosed. Thus, we were able to determine that
the primary neuroanatomical abnormalities that precede dyslexia are not in the
reading network itself, but rather in lower-level areas responsible for auditory
and visual processing and core executive functions. Abnormalities in the reading
network itself were only observed at age 11, after children had learned how to
read. The findings suggest that abnormalities in the reading network are the
consequence of having different reading experiences, rather than dyslexia per se,
whereas the neuroanatomical precursors are predominantly in primary sensory
cortices.
PMID- 25125611
TI - ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting
valine metabolism.
AB - Two siblings with fatal Leigh disease had increased excretion of S-(2
carboxypropyl)cysteine and several other metabolites that are features of 3
hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency, a rare defect in the valine
catabolic pathway associated with Leigh-like disease. However, this diagnosis was
excluded by HIBCH sequencing and normal enzyme activity. In contrast to HIBCH
deficiency, the excretion of 3-hydroxyisobutyryl-carnitine was normal in the
children, suggesting deficiency of short-chain enoyl-CoA hydratase (ECHS1 gene).
This mitochondrial enzyme is active in several metabolic pathways involving fatty
acids and amino acids, including valine, and is immediately upstream of HIBCH in
the valine pathway. Both children were compound heterozygous for a c.473C > A
(p.A158D) missense mutation and a c.414+3G>C splicing mutation in ECHS1. ECHS1
activity was markedly decreased in cultured fibroblasts from both siblings, ECHS1
protein was undetectable by immunoblot analysis and transfection of patient cells
with wild-type ECHS1 rescued ECHS1 activity. The highly reactive metabolites
methacrylyl-CoA and acryloyl-CoA accumulate in deficiencies of both ECHS1 and
HIBCH and are probably responsible for the brain pathology in both disorders.
Deficiency of ECHS1 or HIBCH should be considered in children with Leigh disease.
Urine metabolite testing can detect and distinguish between these two disorders.
PMID- 25125612
TI - Does dominant pedunculopontine nucleus exist?
PMID- 25125613
TI - Reply: Does dominant pedunculopontine nucleus exist?
PMID- 25125615
TI - Learning to be a consultant: what should be taught.
PMID- 25125616
TI - An analysis of clinical consultation activities in clinical pathology: who
requests help and why.
AB - OBJECTIVES: To examine the distribution of callers who made consultation requests
and to identify associations between caller categories and consultation topics.
METHODS: Review of prospectively collected database of consultations. RESULTS:
Direct care personnel made more consultation requests than non-direct care
personnel. Consultation topics varied by caller type. Direct care personnel
requested more consultations on test interpretation and few consultations on test
selection than laboratory personnel. Differences in consultation requests by
primary care physicians and specialists were significant. CONCLUSIONS: At our
laboratory, consultation requests primarily originate from primary care
physicians. Consultation requests vary by caller type.
PMID- 25125614
TI - Diffusion tensor imaging and neurocognition in survivors of childhood acute
lymphoblastic leukaemia.
AB - Survivors of childhood acute lymphoblastic leukaemia are at risk for
neurocognitive impairment, though little information is available on its
association with brain integrity, particularly for survivors treated without
cranial radiation therapy. This study compares neurocognitive function and brain
morphology in long-term adult survivors of childhood acute lymphoblastic
leukaemia treated with chemotherapy alone (n = 36) to those treated with cranial
radiation therapy (n = 39) and to healthy control subjects (n = 23). Mean
(standard deviation) age at evaluation was 24.9 (3.6) years for the chemotherapy
group and 26.7 (3.4) years for the cranial radiation therapy group, while time
since diagnosis was 15.0 (1.7) and 23.9 (3.1) years, respectively. Brain grey and
white matter volume and diffusion tensor imaging was compared between survivor
groups and to 23 healthy controls with a mean (standard deviation) age of 23.1
(2.6) years. Survivors treated with chemotherapy alone had higher fractional
anisotropy in fibre tracts within the left (P < 0.05), but not in the right,
hemisphere when compared to controls. Survivors of acute lymphoblastic leukaemia,
regardless of treatment, had a lower ratio of white matter to intracranial volume
in frontal and temporal lobes (P < 0.05) compared with control subjects.
Survivors of acute lymphoblastic leukaemia treated with chemotherapy alone
performed worse in processing speed (P < 0.001), verbal selective reminding (P =
0.01), and academics (P < 0.05) compared to population norms and performed better
than survivors treated with cranial radiation therapy on verbal selective
reminding (P = 0.02), processing speed (P = 0.05) and memory span (P = 0.009).
There were significant associations between neurocognitive performance and brain
imaging, particularly for frontal and temporal white and grey matter volume.
Survivors of acute lymphoblastic leukaemia treated with chemotherapy alone
demonstrated significant long-term differences in neurocognitive function and
altered neuroanatomical integrity. These results suggest substantial region
specific white matter alterations in survivors of acute lymphoblastic leukaemia
possibly resulting in restricted radial diffusion due to the compaction of
neuronal fibres.
PMID- 25125617
TI - Loss of blast heterogeneity in myelodysplastic syndrome and other chronic myeloid
neoplasms.
AB - OBJECTIVES: Flow cytometry immunophenotyping has been suggested as an adjunctive
technique in the evaluation of myeloid malignancies, especially in the
myelodysplastic syndromes. However, its use has been limited due to complexity
and cost restraints. The goal of this study is to attempt a simpler approach to
flow cytometry immunophenotyping in myeloid neoplasms. METHODS: We analyzed bone
marrow specimens of 45 selected patients and an additional 99 consecutive random
patients using a limited antibody panel. RESULTS: Normal CD34-positive blasts
show a characteristic pattern of CD13/HLA-DR expression, with three readily
identifiable subpopulations. In contrast, myeloid neoplasms frequently show loss
of this heterogeneity. CONCLUSIONS: Analysis of a limited antibody panel with a
focus on CD13/HLA-DR expression provides relatively high specificity and
sensitivity for the detection of myeloid neoplasms.
PMID- 25125619
TI - Rapid detection of the active cardiac glycoside convallatoxin of lily of the
valley using LOCI digoxin assay.
AB - OBJECTIVES: To explore the luminescent oxygen channeling technology-based digoxin
immunoassay (LOCI digoxin assay) for rapid detection of lily of the valley
extract and convallatoxin. The potential in vitro binding of convallatoxin with
Digibind was also evaluated. METHODS: Aliquots of a drug-free serum pool and a
digoxin serum pool were supplemented with lily of the valley extract or
convallatoxin, and then apparent digoxin concentrations were measured using the
LOCI digoxin assay. Mice were administered lily of the valley extract or 50 MUg
of convallatoxin, and digoxin concentrations in serum specimens were measured 1
and 2 hours after gavage. Aliquots of a serum pool supplemented with
convallatoxin or lily of the valley extract were further supplemented with
various concentrations of Digibind and free apparent digoxin concentrations were
measured. RESULTS: Apparent digoxin concentrations were observed when aliquots of
a drug-free serum pool were supplemented with convallatoxin or lily of the valley
extract, and also with convallatoxin or herbal extract. Bidirectional
interference of convallatoxin and lily of the valley extract with serum digoxin
measurement using the LOCI assay was also observed. Digibind was capable of
binding convallatoxin in vitro. CONCLUSIONS: LOCI digoxin assay can be used for
rapid detection of convallatoxin, and Digibind can bind convallatoxin in vitro.
PMID- 25125618
TI - Comparison between invasive breast cancer with extensive peritumoral vascular
invasion and inflammatory breast carcinoma: a clinicopathologic study of 161
cases.
AB - OBJECTIVES: Extensive peritumoral neoplastic lymphovascular invasion (ePVI) is a
marker of aggressiveness in invasive breast carcinoma (BC). METHODS: We explored
the impact of ePVI on different BC subtypes. In a total of 2,116 BCs, 91 ePVI
BCs, 70 inflammatory breast carcinomas (IBCs), and 114 casual BCs as a control
group (CG-BC) were recruited. RESULTS: Patients affected by ePVI-BC were younger,
had larger tumors, higher histologic grade, elevated Ki-67 score, Her2/neu
overexpressed, and more lymph node metastases compared with CG-BC (P < .001).
Interestingly, only younger mean age at diagnosis differentiated patients with
ePVI-BC from patients affected by IBC. ePVI-BC showed a clinical outcome
intermediate between the prognoses of IBC and CG-BC. CONCLUSIONS: Results suggest
that ePVI-BC and IBC may share some pathologic processes, providing a novel
perspective on the heterogeneity of BC. Epidemiologic data and molecular studies
on gene expression features are needed to rationally classify these tumors into
their identified subtypes.
PMID- 25125620
TI - Mesothelin expression in pancreatic mucinous cysts.
AB - OBJECTIVES: Mesothelin (MSLN) is a differentiation antigen found to be
overexpressed in intraductal papillary mucinous neoplasms (IPMNs) and is a
potential treatment target in pancreatic ductal adenocarcinoma. METHODS: From
institutional archives, 114 cases of resected pancreatic mucinous cysts were
identified, including IPMN and mucinous cystic neoplasm (MCN).
Immunohistochemical analysis of MSLN was performed on representative sections.
RESULTS: MSLN was seen more frequently in neoplastic epithelial cells from IPMN
(39/52; P < .0005) and MCN (9/14; P < .0001) compared with unremarkable adjacent
pancreatic and bile ducts (0/57) and benign foveolar and duodenal epithelium
(0/21). When present, MSLN was diffusely expressed in neoplastic epithelium and
only focally expressed in adjacent ducts (8/57). No significant difference was
seen (P = .26) in MLSN expression between IPMN (79%) and MCN (83%) when only
presence or absence was considered. CONCLUSION: Our findings suggest that MLSN
can be used as a marker of neoplastic transformation of epithelial cells in
pancreatic mucinous cysts. The findings can help identify neoplastic mucinous
epithelium.
PMID- 25125621
TI - Evaluation of napsin A, TTF-1, p63, p40, and CK5/6 immunohistochemical stains in
pulmonary neuroendocrine tumors.
AB - OBJECTIVE: A panel of immunohistochemical (IHC) stains frequently used to
subclassify non-small cell lung cancers (NSCLCs) includes napsin A, TTF-1, CK5/6,
p40, and p63. The expression profiles of these stains in neuroendocrine tumors
have not been systematically evaluated. METHOD: Sixty-eight resected pulmonary
neuroendocrine tumors, including 52 typical carcinoids (TCs), eight atypical
carcinoids (ACs), seven small cell carcinomas (SCLCs) and one large cell
neuroendocrine carcinoma (LCNEC), were stained for napsin A, TTF-1, p63, p40, and
CK5/6. Tumors were scored as positive (>1% tumor cells reactive) or negative, and
percentage of reactive tumor cells was recorded. RESULTS: Napsin A, p63, p40, and
CK5/6 were consistently negative in neuroendocrine tumors. TTF-1 was positive in
17 of 52 TCs, 4 of 8 ACs, 5 of 7 SCLCs, and 0 of 1 LCNECs. CONCLUSION: Pulmonary
neuroendocrine tumors have a distinct but nonspecific profile on IHC panel
commonly applied to subclassify NSCLCs. They are napsin A-/p40-/p63-/CK5/6-/TTF
1+/-. Recognizing this profile may have value in separating neuroendocrine tumors
from NSCLCs.
PMID- 25125623
TI - Platelet mapping assay interference due to platelet activation in heparinized
samples.
AB - OBJECTIVES: Thromboelastography Platelet Mapping (TEGPM) is an assay designed to
detect platelet inhibition due to aspirin or clopidogrel-like drugs. The purpose
of this study was to evaluate potential causes of error in the design or
operation of the assay. METHODS: We evaluated percent inhibition of platelets due
to aspirin or clopidogrel using TEGPM, which measures clot viscoelastic maximum
amplitude (MA) after activation with adenosine diphosphate (ADP) or arachidonic
acid (AA) and subtraction of MA due to fibrin (MAFibrin). RESULTS: MAFibrin
measured in heparinized blood showed an unstable increasing pattern in 28% of
samples (16 of 58). The platelet aggregation inhibitor eptifibatide corrected
increasing MAFibrin in 14 of 16 cases, while the thrombin inhibitor argatroban
corrected increasing MAFibrin in six of 16 cases, suggesting that unanticipated
platelet activation/ aggregation was a more important cause of unstable rising
MAFibrin than uninhibited thrombin. The unstable increased MAFibrin falsely
increased percent ADP inhibition on average from 19% to 38% and percent AA
inhibition from 29% to 58%. Heparinized samples showed platelet clumping and had
procoagulant platelet microvesicle levels double those in citrate anticoagulant.
CONCLUSIONS: Unanticipated platelet activation/aggregation occurring in the
heparinized TEGPM samples lead to erroneous percent inhibition results.
PMID- 25125622
TI - A dual-fixed neutrophil substrate improves interpretation of antineutrophil
cytoplasmic antibodies by indirect immunofluorescence.
AB - OBJECTIVES: To determine whether the addition of a formalin-fixed neutrophil
substrate could improve interpretation and prediction of autoantigenic
specificity in antineutrophil cytoplasmic antibody (ANCA) testing. METHODS:
Routine diagnostic samples sent for ANCA testing were analyzed prospectively on a
dual substrate of both ethanol- and formalin-fixed neutrophils. Positive samples
on ethanol-fixed neutrophils were deemed "typical" if formalin-fixed neutrophils
also stained, and "atypical" if not. Indirect immunofluorescence (IIF) results
were correlated with antimyeloperoxidase (MPO) and anti-proteinase 3 (PR3)
results with an enzyme-linked immunosorbent assay (ELISA). RESULTS: Of 1,426
samples, 201 from unique patients were ANCA-positive (200 on IIF, 1 on ELISA
alone). Thirty-two (45%) of 71 typical ANCA staining patterns were positive for
either an anti-MPO or anti-PR3 antibodies, whereas only one (0.8%) of 129
atypical patterns was ELISA-positive, in a patient without systemic vasculitis.
Only one (3%) of 34 ELISA-positive samples had a negative IIF-ANCA (1/1,426
patients, 0.07%), and this patient did not have vasculitis. CONCLUSIONS:
Concomitant staining on formalin fixation of IIF-positive ethanol-fixed ANCA
samples improves the interpretation of ANCA testing and is predictive of
vasculitis autoantigens MPO and PR3.
PMID- 25125624
TI - Aggressive B-cell lymphomas with translocations involving BCL6 and MYC have
distinct clinical-pathologic characteristics.
AB - OBJECTIVES: Recently described, aggressive B-cell lymphomas with genetic
abnormalities involving MYC and BCL2 have been shown to have a poor prognosis
when treated with regimens for diffuse large B-cell lymphomas. Similar data on
cases with concurrent MYC and BCL6 translocation are still scant. Moreover,
little is known regarding the morphologic and immunophenotypic characteristics of
these cases, which further complicates their identification. This study describes
six cases of aggressive B-cell lymphoma with translocations involving MYC and
BCL6. METHODS: Six cases of large B-cell lymphoma with translocation involving
MYC and BCL6 confirmed by fluorescence in situ were identified. The morphologic,
immunophenotypic, and clinical features of the cases were examined. RESULTS: All
the patients were older women, and in 50% of cases, the presentation was
extranodal. In two cases, the liver was involved at presentation. A starry-sky
pattern was a constant feature of the cases in which the morphology could be
reliably assessed. Five of six cases had an immunophenotype corresponding to the
germinal center B cells, and only one was positive for BCL2, an immunophenotype
reminiscent of that of Burkitt lymphoma. CONCLUSIONS: B-cell lymphomas with
translocations involving MYC and BCL6 have morphologic and immunophenotypic
features suggestive of Burkitt lymphoma or gray zone lymphoma, and they tend to
be diagnosed mainly in women, often in extranodal locations.
PMID- 25125626
TI - Recognition and discrimination of tissue-marking dye color by surgical
pathologists: recommendations to avoid errors in margin assessment.
AB - OBJECTIVES: A variety of tissue-marking dye (TMD) colors can be used to indicate
surgical pathology specimen margins; however, the ability of pathologists to
differentiate between specific microscopic margin colors has not been assessed
systematically. This study aimed to evaluate pathologists' accuracy in
identifying TMD color and determine the least ambiguous combinations of colors
for use in surgical pathology. METHODS: Seven colors of TMD were obtained from
three manufacturers and applied to excess formalin-fixed uterine tissue. Study
blocks contained multiple tissue pieces, each marked with a different color from
the same manufacturer. Slides were assessed by eight participants for color and
color distinctness of each piece of tissue. RESULTS: Black, green, red, and blue
TMDs were accurately identified by most participants, but participants had
difficulty identifying violet, orange, and yellow TMDs. Black, green, and blue
TMDs were most commonly rated as "confidently discernable." CONCLUSIONS:
Pathologists have difficulty identifying and distinguishing certain colors of
TMDs. The combined use of certain colors of TMDs (yellow/orange/red, blue/violet,
and red/violet) within the same specimen should be avoided to decrease the risk
of inaccurately reporting specimen margins.
PMID- 25125625
TI - Aberrations of MYC are a common event in B-cell prolymphocytic leukemia.
AB - OBJECTIVES: B-cell prolymphocytic leukemia (B-PLL) remains a controversial
entity, and its molecular pathogenesis is largely unknown. Patients are older,
typically having marked lymphocytosis and splenomegaly in the absence of
lymphadenopathy. It is defined as a mature B-cell leukemia with more than 55%
circulating prolymphocytes. Leukemic mantle cell lymphoma and chronic lymphocytic
leukemia in prolymphocytic transformation must be excluded. METHODS: Case
archives were retrospectively reviewed for B-PLL in patients without a previous
diagnosis of chronic lymphocytic leukemia or other B-cell neoplasm. RESULTS: We
identified six cases of B-PLL with available cytogenetic data, five of which
showed evidence of aberrations in MYC. Three cases showed additional signals for
the MYC gene by fluorescence in situ hybridization (FISH), and two cases
demonstrated t(8;14)MYC/IGH by karyotyping or FISH. High levels of MYC protein
expression were detected in all cases tested with MYC aberrations. CONCLUSIONS:
These results suggest that deregulation of MYC plays an important role in the
pathogenesis of B-PLL and expands the spectrum of B-cell neoplasms associated
with aberrations of MYC.
PMID- 25125628
TI - Utility of immunofluorescence testing for vascular IgA in adult patients with
leukocytoclastic vasculitis.
AB - OBJECTIVES: The purpose of this study was to examine the utility of
immunofluorescence (IF) testing in patients with leukocytoclastic vasculitis
(LCV), particularly with regard to usefulness in the diagnosis of Henoch
Schonlein purpura (HSP). METHODS: We retrospectively analyzed the results of IF
testing in 96 patients with LCV and compared results with clinical criteria and
clinical impression at the time of biopsy by review of the medical record.
RESULTS: Sensitivity and specificity of vascular immunoglobulin A (IgA) for the
diagnosis of HSP were 0.86 and 0.84, respectively. Positive predictive value was
0.48 and negative predictive value was 0.97. Of the 53 patients with LCV who did
not meet clinical criteria for HSP and carried a low clinical suspicion for the
disease at the time of biopsy, seven had moderate to strong staining for vascular
IgA. Only one of these patients was determined to have HSP. CONCLUSIONS: Our data
confirm that vascular IgA is nonspecific and also demonstrate that the utility of
IF studies for vasculitis is influenced by the clinical presentation and the
clinician's level of suspicion for HSP. Our data show that the clinical features
and the overall clinical impression are helpful in selecting which patients are
most likely to benefit from IF testing.
PMID- 25125627
TI - Significant histologic features differentiating cellular fibroadenoma from
phyllodes tumor on core needle biopsy specimens.
AB - OBJECTIVES: Cellular fibroepithelial lesions (CFELs) are a heterogeneous group of
tumors encompassing cellular fibroadenoma (CFA) and phyllodes tumor (PT).
Distinction between the two is challenging on core needle biopsy (CNB) specimens.
The objective of this study was to evaluate histologic features that can help
distinguish PT from CFA on CNB specimens. METHODS: Records of all patients
diagnosed with CFELs on CNB specimens with follow-up excision between January
2002 and December 2012 were retrieved. Histopathologic stromal features were
evaluated on CNB specimens, including mitoses per 10 high-power fields (hpf),
overgrowth, increased cellularity, fragmentation, adipose tissue infiltration,
heterogeneity, subepithelial condensation, and nuclear pleomorphism. RESULTS:
Twenty-seven (42.2%) of 64 were diagnosed as PT (24 benign PTs and three
borderline PTs) and 37 (57.8%) as CFA on excision. All features except for
increased stromal cellularity were statistically significant. The average number
of histologic features seen in PT and CFA was 3.9 and 1.4, respectively (odds
ratio [OR], 7.27; 95% confidence interval [CI], 2.44-21.69; P = .0004). The
average number of mitoses per 10 hpf was 3.0 for PT compared with 0.8 for CFA
(OR, 2.14; 95% CI, 1.18-3.86; P = .01). CONCLUSIONS: The presence of mitoses
(three or more) and/or total histologic features of three or more on CNB
specimens were the most helpful features in predicting PT on excision.
PMID- 25125629
TI - Micropapillary pattern and poorly differentiated clusters represent the same
biological phenomenon in colorectal cancer: a proposal for a change in
terminology.
AB - OBJECTIVES: Colorectal carcinomas (CRCs) with a micropapillary pattern and those
showing high counts of poorly differentiated clusters (PDCs) are characterized by
a higher probability to develop nodal metastases and have a worse prognosis. In
light of the morphologic similarity to the micropapillary component, we aimed to
verify whether PDCs also display an inverted secretory pattern. METHODS: The
immunohistochemical expression of MUC1 and E-cadherin was assessed in a cohort of
CRCs with PDCs and compared with that observed in CRCs without PDCs. RESULTS:
PDCs in our cases always displayed an inverted MUC1 pattern. In addition, we
found abnormal (lost or cytoplasmic) expression of E-cadherin in PDCs.
CONCLUSIONS: The altered expression of MUC1 and E-cadherin may account for the
aggressive behavior and higher metastatic potential of CRCs with high PDC counts
and indicate an epithelial-mesenchymal transition. Our findings suggest that
regardless of the morphologic aspect, PDCs and the micropapillary component may
reflect the same biological phenomenon in CRCs. Thus, we wonder whether the
micropapillary areas should be considered a variant of CRCs or more objectively
counted as PDCs to predict prognosis. We also believe that the term PDC better
describes the biological phenomena underlying this peculiar morphologic aspect in
comparison with the misnomer micropapillary.
PMID- 25125630
TI - Performance characteristics of nested polymerase chain reaction vs real-time
polymerase chain reaction methods for detecting Mycobacterium tuberculosis
complex in paraffin-embedded human tissues.
AB - OBJECTIVES: Nucleic acid amplification tests on formalin-fixed, paraffin-embedded
(FFPE) tissue specimens enable Mycobacterium tuberculosis complex (MTB) detection
and rapid tuberculosis diagnosis in the absence of microbiologic culture tests.
We aimed to evaluate the efficacy of different polymerase chain reaction (PCR)
methods for detecting Mycobacterium species in FFPE tissues. METHODS: We examined
110 FFPE specimens (56 nonmycobacterial cases, 32 MTB, and 22 nontuberculous
mycobacteria [NTM] determined by acid-fast bacilli [AFB] culture) to assess five
PCR methods: nested PCR (N-PCR) (Seeplex MTB Nested ACE Detection; Seegene,
Seoul, South Korea), an in-house real-time PCR (RT-PCR) method, and three
commercial RT-PCR methods (AccuPower MTB RT-PCR [Bioneer, Seoul, Korea], artus M
tuberculosis TM PCR [Qiagen, Hilden, Germany], and AdvanSure tuberculosis/NTM RT
PCR [LG Life Sciences, Seoul, Korea]). RESULTS: The results of N-PCR, in-house RT
PCR, and AdvanSure RT-PCR correlated well with AFB culture results (concordance
rates, 94.3%, 87.5%, and 89.5%, respectively). The sensitivity of N-PCR (87.5%)
was higher than that of the RT-PCR methods, although these differences were not
statistically significant between N-PCR and the in-house and AdvanSure RT-PCR
methods (68.8% and 80.0%, respectively). All the PCR methods had high
specificities, ranging from 98.2% to 100%. Only two NTM cases were detected by
AdvanSure RT-PCR, implying a very low sensitivity. CONCLUSIONS: Well-designed RT
PCR and N-PCR can effectively identify MTB in FFPE specimens.
PMID- 25125631
TI - Correlation between biological marker expression and fluorine-18
fluorodeoxyglucose uptake in hepatocellular carcinoma.
AB - OBJECTIVES: This study investigated the association between several biological
markers and fluorine-18 fluorodeoxyglucose (FDG) uptake in patients with
hepatocellular carcinoma. METHODS: Forty-two patients with hepatocellular
carcinoma who underwent FDG positron emission tomography were included in the
study. Tumor sections were immunohistochemically stained for phosphorylated
signal transducer and activator of transcription 3 (pSTAT3), hypoxia-inducible
factor 1alpha (HIF1alpha), glucose transporter 1 (GLUT1), GLUT2, GLUT3, and
GLUT4. RESULTS: The high standardized uptake value (SUV) group showed larger
tumor size, more frequent vascular invasion, and poorer differentiation compared
with the low SUV group. The high SUV group also showed significantly higher
immunohistochemical expression of pSTAT3, HIF1alpha, and GLUT1. The GLUT1 high
expression group showed higher alpha-fetoprotein (a tumor marker) and poorer
differentiation than did the GLUT1 low-expression group. CONCLUSIONS: Our study
indicates that FDG uptake is associated with the expression of pSTAT3, HIF1alpha,
and GLUT1 in hepatocellular carcinoma. The expression of these proteins shows a
correlation with poor differentiation and vascular invasion.
PMID- 25125632
TI - Utility of nine-color, 11-parameter flow cytometry for detection of plasma cell
neoplasms: a comparison with bone marrow morphologic findings and concurrent M
protein studies in serum and urine.
AB - OBJECTIVES: Multiparameter flow cytometry (MFC) is a widely available laboratory
platform for the evaluation of plasma cell (PC) neoplasms. We assess the
performance of a nine-color MFC assay that uses stain-lyse-fix processing of bone
marrow aspirates, minimal wash steps, and high acquisition rates with analysis of
up to 1.8 * 10(6) cells. METHODS: MFC results were compared with microscopic
examinations, immunohistochemical studies, and serum/urine M-protein measurements
from patients with documented or suspected PC neoplasms. RESULTS: Sensitivity
exceeded that of microscopic examinations, with or without immunohistochemistry.
In patients with PC myeloma, clonal PC detection by MFC fell in concert with M
protein levels. However, in a subset of patients, MFC detected clonal PCs after
serum/urine studies turned negative. CONCLUSIONS: The nine-color analytic
cocktail eliminates duplication of PC gating reagents required for evaluation of
the same epitopes using a five- or six-color approach. Fewer analytic cocktails
result in lower instrument acquisition times per case, a significant factor for
the large data sets required for optimal residual disease assessment. Finally,
concurrent analysis of nine epitopes and two light scatter parameters aids
detection of residual disease, particularly when it is mixed with polyclonal PCs.
PMID- 25125633
TI - Value-based flow testing of chronic lymphoproliferative disorders: a quality
improvement project to develop an algorithm to streamline testing and reduce
costs.
AB - OBJECTIVES: Flow cytometry is essential for the evaluation of lymphoproliferative
disorders (LPDs) and their classification. Flow panels routinely incorporate a
large array of antibodies, making testing complex and expensive; such panels are
likely unnecessary in benign cases or those with straightforward diagnoses. Our
aim was to develop a more cost-effective testing strategy based on a
retrospective analysis of flow studies for possible LPDs in blood. METHODS: We
identified LPD frequencies and types, as well as associated results with patient
age and absolute lymphocyte count. RESULTS: We found that the likelihood of LPDs
increased with patient age and absolute lymphocyte count and that CD5-positive
LPD was the most common LPD diagnosed in our institution (71% of LPDs). Using
these data, we devised flow-testing algorithms with a screening test for patients
at low risk of disease and a focus on CD5-positive LPD detection, with reflexing
as needed. CONCLUSIONS: We project this approach will result in a 40% decrease in
antibody utilization.
PMID- 25125635
TI - Long-term effects of continuous positive airway pressure on blood pressure and
prognosis in hypertensive patients with coronary heart disease and obstructive
sleep apnea: a randomized controlled trial.
AB - BACKGROUND: Obstructive sleep apnea (OSA) can result in hypertension and
significantly increase cardiovascular morbidity and mortality. There are few
reports on the long-term effects of continuous positive airway pressure (CPAP) on
blood pressure in patients with uncontrolled hypertension with coronary heart
disease (CHD) and OSA. METHODS: We conducted a prospective, long-term follow-up
study in 83 patients with uncontrolled hypertension, CHD, and OSA randomized to
control or CPAP groups. Daytime systolic blood pressure (SBP), diastolic blood
pressure (DBP), and severe cardiovascular and cerebrovascular events (SCCEs) were
recorded at baseline and follow-up. RESULTS: Seventy-three patients completed the
study with a median follow-up of 36 (interquartile range = 24-54) months. The 2
groups had similar characteristics at baseline. CPAP was used for 4.5+/-1.1
hour/night. SBP in the CPAP group was significantly reduced at follow-up (143+/-7
mm Hg vs. 139+/-7 mm Hg, P = 0.04), and SBP decreased by 8mm Hg (95% confidence
interval = 1.4-9.9; P = 0.01). Hypertension control was improved (CPAP, 69.4% for
CPAP users vs. 43.2% for control subjects; P = 0.02); however, DBP did not reach
statistical difference between the groups (81+/-10 mm Hg vs. 79+/-8 mm Hg; P =
0.49). In the CPAP group, the Epworth Sleepiness Scale was markedly reduced
(7.0+/-3.4 vs. 3.7+/-2.3; P < 0.001). There was 1 SCCE in the CPAP group (heart
failure), and 5 SCCEs in the control group (acute myocardial infarction: 2 (with
1 death); stroke: 3), but there was no significant difference identified.
CONCLUSIONS: Long-term CPAP application in uncontrolled hypertension with CHD and
OSA significantly reduced daytime SBP, improved hypertension control and daytime
sleepiness, and decreased the trend in SCCEs compared with control subjects.
CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02059993.
PMID- 25125636
TI - Association between invasively measured central aortic pressure and left
ventricular diastolic function in patients undergoing coronary angiography.
AB - BACKGROUND: Because of the invasive nature of catheterization, limited
information is available on hemodynamic interaction between the left ventricle
and aorta using invasive aortic pressure monitoring. Our aim was to investigate
whether parameters of invasively measured central aortic pressure waveform were
related with those of left ventricular (LV) diastolic function. METHODS: A total
of 153 consecutive stable patients (mean age = 64+/-11 years; 62% men) undergoing
invasive coronary angiography (ICA) and transthoracic echocardiography (TTE) were
prospectively evaluated. Central aortic pressure waveform was obtained at the
ascending aorta using a pigtail catheter before ICA. We calculated pulse pressure
(PP), fractional PP (FPP; the ratio of PP to mean pressure), pulsatility index
(PI; the ratio of PP to diastolic pressure), augmentation index, wave reflection
time, and ejection duration and analyzed their associations with parameters of LV
diastolic function in TTE. RESULTS: Most patients (n = 135/153; 88.2%) had
significant stenosis (>=50%) of >=1 epicardial coronary arteries. In multiple
linear regression analyses, e' and E/e' were significantly correlated with PP,
FPP, and PI even after adjustment for potential confounders. There were no
significant correlations between other parameters of LV diastolic function,
including E/A, deceleration time, and left atrial volume index and parameters of
central aortic pressure wave. CONCLUSIONS: Invasively measured central aortic PP,
FPP, and PI were independently associated with e' and E/e' in patients undergoing
ICA. This result adds to the evidence of a close interaction between LV diastolic
function and aortic stiffness in this population.
PMID- 25125637
TI - Complete Nucleotide Sequence of pVv01, a P1-Like Plasmid Prophage of Vibrio
vulnificus.
AB - We report here the 79,263-bp plasmid pVv01 isolated from Vibrio vulnificus. pVv01
is closely related to the Vibrio plasmid p0908 and shows some similarities to
phage P1. Unlike p0908, pVv01 represents an intact prophage inducible by
mitomycin C. PVv01 phage particles revealed a myoviridal morphology and lytic
activity.
PMID- 25125638
TI - Draft Genome Sequences of Propionibacterium acnes Type Strain ATCC6919 and
Antibiotic-Resistant Strain HL411PA1.
AB - Propionibacterium acnes is a major skin commensal and is associated with acne
vulgaris, the most common skin disease. Here we report the draft genome sequences
of two P. acnes strains, the type strain ATCC6919 and an antibiotic-resistant
strain, HL411PA1.
PMID- 25125639
TI - Complete genome sequence of porcine epidemic diarrhea virus in Vietnam.
AB - Porcine epidemic diarrhea virus (PEDV) has emerged in Vietnam since 2009. Herein,
full-length genome sequences are reported for three PEDV isolates from pigs
displaying severe diarrhea from farms located in northern and southern provinces
of Vietnam. The results provide more understanding of the molecular
characteristics of PEDV in Vietnam.
PMID- 25125640
TI - Complete Genome Sequence of an Alkane Degrader, Alcanivorax sp. Strain NBRC
101098.
AB - Alcanivorax sp. strain NBRC 101098 was isolated from seawater in Japan. Strain
NBRC 101098 is able to degrade various types of n-alkanes. Here, we report the
complete genome of strain NBRC 101098.
PMID- 25125641
TI - Whole-Genome Sequence of Streptococcus suis Serotype 4 Reference Strain 6407.
AB - We report here the second complete genome sequence of Streptococcus suis serotype
4 (strain 6407). The genome is 2,292,360 bp in length, covering 2,239 coding
sequences, 58 tRNAs, and 4 rRNA loci.
PMID- 25125642
TI - Integrated metagenomics and metatranscriptomics analyses of root-associated soil
from transgenic switchgrass.
AB - The benefits of using transgenic switchgrass with decreased levels of caffeic
acid 3-O-methyltransferase (COMT) as biomass feedstock have been clearly
demonstrated. However, its effect on the soil microbial community has not been
assessed. Here we report metagenomic and metatranscriptomic analyses of root
associated soil from COMT switchgrass compared with nontransgenic counterparts.
PMID- 25125643
TI - Draft Genome Sequence of Microbacterium sp. Strain CH12i, Isolated from Shallow
Groundwater in Cape Hallett, Antarctica.
AB - The Antarctic continent is largely covered by an expansive ice sheet, but it
harbors diverse terrestrial and aquatic habitats in the coastal ice-free
continental margins. Here we present the draft genome of Microbacterium sp.
CH12i, which was isolated from hypersaline, alkaline, and nutrient-rich
groundwater from Cape Hallett, northern Victoria Land, Antarctica.
PMID- 25125644
TI - Draft Genome Sequence of Nonlabens ulvanivorans, an Ulvan-Degrading Bacterium.
AB - Here we report the draft genome sequence of the bacterium Nonlabens ulvanivorans,
which was recently isolated. To our knowledge, this is the first published genome
of a characterized ulvan-degrading bacterium. Revealing the ulvan utilization
pathways may provide access to a vast marine biomass source that has yet to be
exploited.
PMID- 25125645
TI - High-Quality Draft Genomes of Two Vibrio parahaemolyticus Strains Aid in
Understanding Acute Hepatopancreatic Necrosis Disease of Cultured Shrimps in
Mexico.
AB - The high-quality draft genomes of two Vibrio parahaemolyticus strains, one that
causes the acute hepatopancreatic necrosis disease (AHPND) in cultured shrimps
(FIM-S1708(+)), and another that does not (FIM-S1392(-)) are reported. A
chromosome-scale assembly for the FIM-S1392(-) genome is reported here. The
analysis of the two genomes gives some clues regarding the genomic differences
between the strains.
PMID- 25125646
TI - Whole-genome sequences of three symbiotic endozoicomonas strains.
AB - Members of the genus Endozoicomonas associate with a wide range of marine
organisms. Here, we report on the whole-genome sequencing, assembly, and
annotation of three Endozoicomonas type strains. These data will assist in
exploring interactions between Endozoicomonas organisms and their hosts, and it
will aid in the assembly of genomes from uncultivated Endozoicomonas spp.
PMID- 25125647
TI - Whole-Genome Sequence of a Multidrug-Resistant Mycobacterium tuberculosis Beijing
Sequence Type 10 Isolate from an Outbreak in Thailand.
AB - Infections with the Beijing family of Mycobacterium tuberculosis occur worldwide
and are endemic in Asian countries. We present the draft genome sequence of
DS6701, a multidrug-resistant M. tuberculosis Beijing strain of sequence type 10.
The isolate is a representative of strains isolated from a multidrug-resistant
tuberculosis outbreak in Thailand.
PMID- 25125648
TI - Draft Genome Sequence of Burkholderia sordidicola S170, a Potential Plant Growth
Promoter Isolated from Coniferous Forest Soil in the Czech Republic.
AB - Burkholderia species are key players in the accumulation of carbon from cellulose
decomposition in coniferous forest ecosystems. We report here the draft genome of
Burkholderia sordidicola strain S170, containing features associated with known
genes involved in plant growth promotion, the biological control of plant
diseases, and green remediation technologies.
PMID- 25125649
TI - Draft Genome Sequence of Haloferax sp. Strain ATB1, Isolated from a Semi-Arid
Region in the Brazilian Caatinga.
AB - Organisms in the Haloferax genus are extreme halophiles that grow in environments
with pH values between 4 and 12, and temperatures between 0 degrees C and 60
degrees C. In the present study, a draft of the first Haloferax sp. strain ATB1
genome isolated from the region of Cariri (in Paraiba State, Brazil) is
presented.
PMID- 25125650
TI - A Gapless, Unambiguous Genome Sequence of the Enterohemorrhagic Escherichia coli
O157:H7 Strain EDL933.
AB - Escherichia coli EDL933 is the prototypic strain for enterohemorrhagic E. coli
serotype O157:H7, associated with deadly food-borne outbreaks. Because the
publicly available sequence of the EDL933 genome has gaps and >6,000 ambiguous
base calls, we here present an updated high-quality, unambiguous genome sequence
with no assembly gaps.
PMID- 25125651
TI - Draft Genome Sequence of an Atypical Strain of Streptococcus pneumoniae Isolated
from a Respiratory Infection.
AB - Next-generation sequencing was used to investigate an unknown clinical
respiratory infection. This new strain of Streptococcus pneumoniae, ASVL_JC_0001,
was isolated from a clinical specimen from a patient with bronchitis and
pulmonary inflammation. The draft genome sequence, obtained with an Illumina
MiSeq sequencing system, consists of 83 large contigs, a total of 2,092,532 bp
long, and has a GC content of 40.3%.
PMID- 25125652
TI - Draft Genome Sequence of Staphylococcus chromogenes Strain MU 970, Isolated from
a Case of Chronic Bovine Mastitis.
AB - Coagulase-negative staphylococcal species are a common cause of subclinical
bovine mastitis, with Staphylococcus chromogenes being one of the most frequently
identified species in these cases. The draft genome sequence of an S. chromogenes
isolate (MU 970) recovered from the milk of a cow with a chronic intramammary
infection is reported here.
PMID- 25125653
TI - Draft Genome Sequence of Rifamycin Derivatives Producing Amycolatopsis
mediterranei Strain DSM 46096/S955.
AB - Amycolatopsis mediterranei DSM 46096 produces antibiotics of the rifamycin
family, 27-demethoxy-27-hydroxyrifamycin B, 25-desacetyl-27-demethoxy-27
hydroxyrifamycin, and 27-demethoxy-27-hydroxyrifamycin SV, which are effective
against Gram-negative bacteria. Here, we present the draft genome of A.
mediterranei 46096 (approx. 10.2 Mbp) having 104 contigs with a GC content of
71.3% and 9,382 coding sequences.
PMID- 25125654
TI - Draft Genome Sequence of Haloalkaliphilic Exiguobacterium sp. Strain AB2 from
Manleluag Ophiolitic Spring, Philippines.
AB - Exiguobacterium sp. AB2 is a haloalkaliphilic bacterium isolated from a
hyperalkaline spring in Manleluag, Pangasinan, Philippines. Sequencing of
bacterial DNA assembled a 2.85 MB draft genome. Analysis suggests the presence of
genes for tolerance to stresses such as elevated pH and salt concentrations and
toxic metals.
PMID- 25125655
TI - EGFR blockade enriches for lung cancer stem-like cells through Notch3-dependent
signaling.
AB - Mutations in the epidermal growth factor receptor (EGFR) are the most common
actionable genetic abnormalities yet discovered in lung cancer. However,
targeting these mutations with kinase inhibitors is not curative in advanced
disease and has yet to demonstrate an impact on potentially curable, early-stage
disease, with some data suggesting adverse outcomes. Here, we report that
treatment of EGFR-mutated lung cancer cell lines with erlotinib, while showing
robust cell death, enriches the ALDH(+) stem-like cells through EGFR-dependent
activation of Notch3. In addition, we demonstrate that erlotinib treatment
increases the clonogenicity of lung cancer cells in a sphere-forming assay,
suggesting increased stem-like cell potential. We demonstrate that inhibition of
EGFR kinase activity leads to activation of Notch transcriptional targets in a
gamma secretase inhibitor-sensitive manner and causes Notch activation, leading
to an increase in ALDH high(+) cells. We also find a kinase-dependent physical
association between the Notch3 and EGFR receptors and tyrosine phosphorylation of
Notch3. This could explain the worsened survival observed in some studies of
erlotinib treatment at early-stage disease, and suggests that specific dual
targeting might overcome this adverse effect.
PMID- 25125657
TI - Cytokine-like molecule CCDC134 contributes to CD8+ T-cell effector functions in
cancer immunotherapy.
AB - CCDC134 is a poorly characterized secreted protein that may act as an immune
cytokine. Here, we show that CCDC134 is differentially expressed on resting and
activated immune cells and that it promotes CD8(+) T-cell activation,
proliferation, and cytotoxicity by augmenting expression of the T-cell effector
molecules IFNgamma, TNFalpha, granzyme B, and perforin. CCDC134 facilitated
infiltration of CD8(+) T cells with enhanced cytolytic activity into tumors,
demonstrating strong antitumor effects in a CD8(+) T-cell-dependent manner.
Mechanistically, in CD8(+) T cells, exposure to CCDC134 promoted cell
proliferation through the JAK3-STAT5 pathway, a classic feature of many cytokines
of the common gamma-chain (gamma(c)) cytokine receptor family. Overall, our
results provide evidence that CCDC134 may serve as a member of the gamma(c)
cytokine family and illustrate its potent antitumor effects by augmenting CD8(+)
T-cell-mediated immunity.
PMID- 25125656
TI - Vaccine-elicited CD8+ T cells cure mesothelioma by overcoming tumor-induced
immunosuppressive environment.
AB - Eradicating malignant tumors by vaccine-elicited host immunity remains a major
medical challenge. To date, correlates of immune protection remain unknown for
malignant mesothelioma. In this study, we demonstrated that antigen-specific
CD8(+) T-cell immune response correlates with the elimination of malignant
mesothelioma by a model PD-1-based DNA vaccine. Unlike the nonprotective tumor
antigen WT1-based DNA vaccines, the model vaccine showed complete and long
lasting protection against lethal mesothelioma challenge in immunocompetent
BALB/c mice. Furthermore, it remained highly immunogenic in tumor-bearing animals
and led to therapeutic cure of preexisting mesothelioma. T-cell depletion and
adoptive transfer experiments revealed that vaccine-elicited CD8(+) T cells
conferred to the protective efficacy in a dose-dependent way. Also, these CD8(+)
T cells functioned by releasing inflammatory IFNgamma and TNFalpha in the
vicinity of target cells as well as by initiating TRAIL-directed tumor cell
apoptosis. Importantly, repeated DNA vaccinations, a major advantage over live
vectored vaccines with issues of preexisting immunity, achieve an active
functional state, not only preventing the rise of exhausted PD-1(+) and Tim-3(+)
CD8(+) T cells but also suppressing tumor-induced myeloid-derived suppressive
cells and Treg cells, with the frequency of antigen-specific CD8(+) T cells
inversely correlating with tumor mass. Our results provide new insights into
quantitative and qualitative requirements of vaccine-elicited functional CD8(+) T
cells in cancer prevention and immunotherapy.
PMID- 25125659
TI - AXL inhibition sensitizes mesenchymal cancer cells to antimitotic drugs.
AB - Molecularly targeted drug therapies have revolutionized cancer treatment;
however, resistance remains a major limitation to their overall efficacy.
Epithelial-to-mesenchymal transition (EMT) has been linked to acquired resistance
to tyrosine kinase inhibitors (TKI), independent of mutational resistance
mechanisms. AXL is a receptor tyrosine kinase associated with EMT that has been
implicated in drug resistance and has emerged as a candidate therapeutic target.
Across 643 human cancer cell lines that were analyzed, elevated AXL was strongly
associated with a mesenchymal phenotype, particularly in triple-negative breast
cancer and non-small cell lung cancer. In an unbiased screen of small-molecule
inhibitors of cancer-relevant processes, we discovered that AXL inhibition was
specifically synergistic with antimitotic agents in killing cancer cells that had
undergone EMT and demonstrated associated TKI resistance. However, we did not
find that AXL inhibition alone could overcome acquired resistance to EGFR TKIs in
the EMT setting, as previously reported. These findings reveal a novel
cotreatment strategy for tumors displaying mesenchymal features that otherwise
render them treatment refractory.
PMID- 25125658
TI - NQO1 suppresses NF-kappaB-p300 interaction to regulate inflammatory mediators
associated with prostate tumorigenesis.
AB - NADPH reductase NAD(P)H: quinone oxidoreductase 1 (NQO1) is needed to maintain a
cellular pool of antioxidants, and this enzyme may contribute to tumorigenesis on
the basis of studies in NQO1-deficient mice. In this work, we sought deeper
insights into how NQO1 contributes to prostate carcinogenesis, a setting in which
oxidative stress and inflammation are established contributors to disease
development and progression. In the TRAMP mouse model of prostate cancer, NQO1
was highly expressed in tumor cells. NQO1 silencing in prostate cancer cells
increased levels of nuclear IKKalpha and NF-kappaB while decreasing the levels of
p53, leading to interactions between NF-kappaB and p300 that reinforce survival
signaling. Gene expression analysis revealed upregulation of a set of immune
associated transcripts associated with inflammation and tumorigenesis in cells in
which NQO1 was attenuated, with IL8 confirmed functionally in cell culture as one
key NQO1-supported cytokine. Notably, NQO1-silenced prostate cancer cells were
more resistant to androgen deprivation. Furthermore, NQO1 inhibition increased
migration, including under conditions of androgen deprivation. These results
reveal a molecular link between NQO1 expression and proinflammatory cytokine
signaling in prostate cancer. Furthermore, our results suggest that altering
redox homeostasis through NQO1 inhibition might promote androgen-independent cell
survival via opposing effects on NF-kappaB and p53 function.
PMID- 25125660
TI - PAK1 tyrosine phosphorylation is required to induce epithelial-mesenchymal
transition and radioresistance in lung cancer cells.
AB - The p21-activated Ser/Thr kinase 1 (PAK1) kinase has an essential role in
tumorigenesis and cell survival in many cancers, but its regulation is not fully
understood. In this study, we showed that in response to irradiation of lung
cancer cells, PAK1 was upregulated, tyrosine phosphorylated, and translocated to
the nucleus. Tyrosine phosphorylation relied upon JAK2 kinase activity and was
essential for PAK1 protein stability and binding to Snail. This radiation-induced
JAK2-PAK1-Snail signaling pathway increased epithelial-mesenchymal transition
(EMT) by regulating epithelial and mesenchymal cell markers. Notably, JAK2
inhibitors mediated radiosensitization and EMT blockade in a mouse xenograft
model of lung cancer. Taken together, our findings offered evidence that JAK2
phosphorylates and stabilizes functions of PAK1 that promote EMT and
radioresistance in lung cancer cells, with additional implications for the use of
JAK2 inhibitors as radiosensitizers in lung cancer treatment.
PMID- 25125661
TI - Transcriptional dynamics in colorectal carcinogenesis: new insights into the role
of c-Myc and miR17 in benign to cancer transformation.
AB - Colorectal cancer develops in a sequential, evolutionary process, leading to a
heterogenic tumor. Comprehensive molecular studies of colorectal cancer have been
previously performed; still, the process of carcinogenesis is not fully
understood. We utilized gene expression patterns from 94 samples including
normal, adenoma, and adenocarcinoma colon biopsies and performed a coexpression
network analysis to determine gene expression trajectories of 8,000 genes across
carcinogenesis. We found that the majority of gene expression changes occur in
the transition from normal tissue to adenoma. The upregulated genes, known to be
involved in cellular proliferation, included c-Myc along with its targets. In a
cellular model system, we show that physiologic upregulation of c-Myc can lead to
cellular proliferation without DNA replication stress. Our analysis also found
that carcinogenesis involves a progressive downregulation of genes that are
markers of colonic tissue and propose that this reflects a perturbed
differentiation of colon cells during carcinogenesis. The analysis of miRNAs
targets pointed toward the involvement of miR17 in the regulation of colon cell
differentiation. Finally, we found that copy-number variations (CNV) enriched in
colon adenocarcinoma tend to occur in genes whose expression changes already in
adenoma, with deletions occurring in genes downregulated and duplications in
genes upregulated in adenomas. We suggest that the CNVs are selected to reinforce
changes in gene expression, rather than initiate them. Together, these findings
shed new light into the molecular processes that underlie the transformation of
colon tissue from normal to cancer and add a temporal context that has been
hitherto lacking.
PMID- 25125662
TI - Translesion polymerase eta is upregulated by cancer therapeutics and confers
anticancer drug resistance.
AB - DNA repair processes are a key determinant of the sensitivity of cancer cells to
DNA-damaging chemotherapeutics, which may induce certain repair genes as a
mechanism to promote resistance. Here, we report the results of a screen for
repair genes induced in cancer cells treated with DNA crosslinking agents, which
identified the translesion polymerase eta (PolH) as a p53-regulated target acting
as one defense against interstrand crosslink (ICL)-inducing agents. PolH was
induced by fotemustine, mafosfamide, and lomustine in breast cancer, glioma, and
melanoma cells in vitro and in vivo, with similar inductions observed in normal
cells such as lymphocytes and diploid fibroblasts. PolH contributions to the
protection against ICL-inducing agents were evaluated by its siRNA-mediated
attenuation in cells, which elevated sensitivity to these drugs in all tumor cell
models. Conversely, PolH overexpression protected cancer cells against these
drugs. PolH attenuation reduced repair of ICL lesions as measured by host cell
reactivation assays and enhanced persistence of gammaH2AX foci. Moreover, we
observed a strong accumulation of PolH in the nucleus of drug-treated cells along
with direct binding to damaged DNA. Taken together, our findings implicated PolH
in ICL repair as a mechanism of cancer drug resistance and normal tissue
protection.
PMID- 25125663
TI - Evaluation of a metal artifacts reduction algorithm applied to postinterventional
flat panel detector CT imaging.
AB - BACKGROUND AND PURPOSE: Flat panel detector CT images are degraded by streak
artifacts caused by radiodense implanted materials such as coils or clips. A new
metal artifacts reduction prototype algorithm has been used to minimize these
artifacts. The application of this new metal artifacts reduction algorithm was
evaluated for flat panel detector CT imaging performed in a routine clinical
setting. MATERIALS AND METHODS: Flat panel detector CT images were obtained from
59 patients immediately following cerebral endovascular procedures or as
surveillance imaging for cerebral endovascular or surgical procedures previously
performed. The images were independently evaluated by 7 physicians for metal
artifacts reduction on a 3-point scale at 2 locations: immediately adjacent to
the metallic implant and 3 cm away from it. The number of visible vessels before
and after metal artifacts reduction correction was also evaluated within a 3-cm
radius around the metallic implant. RESULTS: The metal artifacts reduction
algorithm was applied to the 59 flat panel detector CT datasets without
complications. The metal artifacts in the reduction-corrected flat panel detector
CT images were significantly reduced in the area immediately adjacent to the
implanted metal object (P = .05) and in the area 3 cm away from the metal object
(P = .03). The average number of visible vessel segments increased from 4.07 to
5.29 (P = .1235) after application of the metal artifacts reduction algorithm to
the flat panel detector CT images. CONCLUSIONS: Metal artifacts reduction is an
effective method to improve flat panel detector CT images degraded by metal
artifacts. Metal artifacts are significantly decreased by the metal artifacts
reduction algorithm, and there was a trend toward increased vessel-segment
visualization.
PMID- 25125664
TI - High-resolution CT findings in children with a normal pinna or grade I microtia
and unilateral mild stenosis of the external auditory canal.
AB - SUMMARY: A subset of patients presents with unilateral conductive hearing loss, a
normal pinna or grade I microtia, and mild external auditory canal stenosis. The
physical findings of microtia and a small external canal are commonly absent or
subtle in this group of patients, who are being commonly referred for imaging to
evaluate isolated conductive hearing loss. We present a case series of patients
with unilateral conductive hearing loss and characteristic ossicular
abnormalities, commonly anterior fixation of the malleus. All patients had a
significantly increased distance from the cochlear promontory to the handle of
the malleus and an abnormal incudostapedial angle, indicative of an abnormal
ossicular position and/or morphology. Successful surgical reconstruction of the
ossicular chain was attempted and accomplished in 3 patients.
PMID- 25125665
TI - One-year MR angiographic and clinical follow-up after intracranial mechanical
thrombectomy using a stent retriever device.
AB - BACKGROUND AND PURPOSE: Little is known about the consequences of arterial wall
damage that may be due to mechanical endovascular thrombectomy. Our aim was to
perform 1-year MR angiographic and clinical follow-up of patients treated with
mechanical endovascular thrombectomy using the Solitaire device. MATERIALS AND
METHODS: Patients with stroke treated between August 2010 and July 2012 were
prospectively evaluated with a minimum follow-up of 1 year after mechanical
endovascular thrombectomy. Angiographic follow-up was performed on a 3T MR
imaging scanner and included intracranial artery TOF MRA and supra-aortic artery
gadolinium-enhanced MRA. Images were assessed to detect arterial abnormalities
(stenosis, occlusion, dilation) and were compared with the final post-mechanical
endovascular thrombectomy run to differentiate delayed and pre-existing
abnormalities. Clinical evaluation was performed with the mRS and the 36-Item
Short-Form Health Survey questionnaire quality-of-life scale. RESULTS: Thirty
nine patients were angiographically assessed at the mean term of 19 +/- 4 months.
MRA showed intracranial artery abnormalities in 10 patients, including 5 delayed
intracranial artery abnormalities in 4 patients (4 stenoses and 1 dilation), 4
cases of pre-existing intracranial artery stenosis, and 2 occlusions. Pre
existing etiologic cervical artery stenosis or occlusion was observed in 2
patients. All these patients remained asymptomatic during the follow-up period. A
significant clinical improvement was observed at 1-year follow-up in comparison
with 3-month follow-up (P < .0001), with a good outcome achieved in 62.5% of
patients and an acceptable quality of life restored. CONCLUSIONS: One-year follow
up identifies delayed asymptomatic arterial abnormalities in patients treated
with the Solitaire device.
PMID- 25125666
TI - Surpass flow diverter in the treatment of intracranial aneurysms: a prospective
multicenter study.
AB - BACKGROUND AND PURPOSE: Incomplete occlusion and recanalization of large and wide
neck brain aneurysms treated by endovascular therapy remains a challenge. We
present preliminary clinical and angiographic results of an experimentally
optimized Surpass flow diverter for treatment of intracranial aneurysms in a
prospective, multicenter, nonrandomized, single-arm study. MATERIALS AND METHODS:
At 24 centers, 165 patients with 190 intracranial aneurysms of the anterior and
posterior circulations were enrolled. The primary efficacy end point was the
percentage of intracranial aneurysms with 100% occlusion on 6-month DSA. The
primary safety end point was neurologic death and any stroke through a minimum
follow-up of 6 months. RESULTS: Successful flow-diverter delivery was achieved in
161 patients with 186 aneurysms (98%); the mean number of devices used per
aneurysm was 1.05. Clinical follow-up (median, 6 months) of 150 patients (93.2%),
showed that the primary safety end point occurred in 18 subjects. Permanent
neurologic morbidity and mortality were 6% and 2.7%, respectively. Morbidity
occurred in 4% and 7.4% of patients treated for aneurysms of the anterior and
posterior circulation, respectively. Neurologic death during follow-up was
observed in 1.6% and 7.4% of patients with treated intracranial aneurysms of the
anterior and posterior circulation, respectively. Ischemic stroke at <=30 days,
SAH at <=7 days, and intraparenchymal hemorrhage at <=7 days were encountered in
3.7%, 2.5%, and 2.5% of subjects, respectively. No disabling ischemic strokes at
>30 days or SAH at >7 days occurred. New or worsening cranial nerve deficit was
observed in 2.7%. Follow-up angiography available in 158 (86.8%) intracranial
aneurysms showed 100% occlusion in 75%. CONCLUSIONS: Clinical outcomes of the
Surpass flow diverter in the treatment of intracranial aneurysms show a safety
profile that is comparable with that of stent-assisted coil embolization.
Angiographic results showed a high rate of intracranial aneurysm occlusion.
PMID- 25125667
TI - Middle cerebral artery stenosis in patients with acute ischemic stroke and TIA in
Israel.
AB - BACKGROUND AND PURPOSE: Middle cerebral artery stenosis is not frequent but a
well-established cause of first and recurrent ischemic stroke. Our aim was to
investigate middle cerebral artery stenosis in the biethnic (Jewish and Arab)
population of patients with acute ischemic stroke and transient ischemic attack
in northern Israel. MATERIALS AND METHODS: The study population included 1344
patients from the stroke data registry who had been hospitalized in the
neurologic department because of acute ischemic stroke (1041) or TIA (303) and
had undergone transcranial Doppler sonographic examination during the
hospitalization. RESULTS: Of the 1344 patients, 120 (8.9%) were found to have MCA
stenosis. The patients with intracranial stenosis were older and had more
vascular risk factors (hypertension, diabetes, and hyperlipidemia) and vascular
diseases (ischemic heart and peripheral vascular disease) than those without
intracranial stenosis. Logistic regression analysis revealed that diabetes (P =
.002) and peripheral vascular disease (P = .01), but not ethnicity, were
independent and significant predictors for the presence of MCA stenosis.
CONCLUSIONS: An independent and significant correlation was found between MCA
stenosis and vascular risk factors (diabetes mellitus) and vascular diseases,
thus emphasizing the similarity of intracranial MCA stenosis and other vascular
diseases originating from atherosclerosis. There was no influence of ethnicity on
intracranial stenosis in our population.
PMID- 25125669
TI - Expanding minimally invasive innovation to complex mitral reoperations.
PMID- 25125670
TI - Nitric oxide (NO): an emerging target for the treatment of glaucoma.
AB - The predominant risk factor for the progression of glaucoma is an increase in
IOP, mediated via a reduction in aqueous outflow through the conventional
(trabecular meshwork and Schlemm's canal) outflow pathway. Current IOP lowering
pharmacological strategies target the uveoscleral (nonconventional) outflow
pathway or aqueous humor production; however, to date no therapy that primarily
targets the conventional pathway exists. Nitric oxide (NO) is an intracellular
signaling molecule produced by endogenous NO synthases, well-known for its key
role in vasodilation, through its action on smooth muscle cells. Under
physiological conditions, NO mediates a multitude of diverse ocular effects,
including maintenance of IOP. Nitric oxide donors have been shown to mediate IOP
lowering effects in both preclinical models and clinical studies, primarily
through cell volume and contractility changes in the conventional outflow
tissues. This review is focused on evaluating the current knowledge of the role
and mechanism of action of endogenous NO and NO donors in IOP regulation. Data on
key additional functions of NO in glaucoma pathology (i.e., ocular blood flow and
effects on optic neuropathy) are also summarized. The potential for future
therapeutic application of NO in the treatment of glaucoma is then discussed.
PMID- 25125671
TI - Choroidal thickness and axial length.
PMID- 25125672
TI - Author response: Choroidal thickness and axial length.
PMID- 25125673
TI - Anterior segment parameters during unilateral acute primary angle closure.
PMID- 25125674
TI - Author response: Anterior segment parameters during unilateral acute primary
angle closure.
PMID- 25125676
TI - Aspergillus fumigatus harbouring the sole Y121F mutation shows decreased
susceptibility to voriconazole but maintained susceptibility to itraconazole and
posaconazole.
AB - OBJECTIVES: Voriconazole, itraconazole and posaconazole are members of the azole
family and widely used for the treatment of aspergillosis. They act by inhibiting
the activity of the fungal Cyp51A enzyme. The emergence of environmental azole
resistant Aspergillus fumigatus strains raises major concerns for human health.
METHODS: Recently, a new cyp51A-mediated resistance mechanism (namely
TR46/Y121F/T289A) was described in clinical samples and patient-frequented
environmental sites. In an azole-naive patient, we isolated an A. fumigatus
strain that was not susceptible to voriconazole but was susceptible to
itraconazole and posaconazole. RESULTS: A molecular analysis indicated a single
Y121F substitution without the TR46 or T289A alterations, which to our knowledge
has never been reported. Structure modelling and molecular dynamics offered an
explanation for the resistance profile consistent with the structural differences
between the three azoles. CONCLUSIONS: Taken together, these observations suggest
an original mechanism conferring resistance to azoles mediated by cyp51A of
environmental origin. This uncommon susceptibility pattern might represent a
'missing link' between the wild-type A. fumigatus and the fully azole-resistant
strain harbouring the TR46/Y121F/T289A mutations.
PMID- 25125677
TI - Vancomycin plus ceftaroline shows potent in vitro synergy and was successfully
utilized to clear persistent daptomycin-non-susceptible MRSA bacteraemia.
PMID- 25125675
TI - Inhibition of endoglin-GIPC interaction inhibits pancreatic cancer cell growth.
AB - Endoglin, a 180-kDa disulfide-linked homodimeric transmembrane receptor protein
mostly expressed in tumor-associated endothelial cells, is an endogenous binding
partner of GAIP-interacting protein, C terminus (GIPC). Endoglin functions as a
coreceptor of TbetaRII that binds TGFbeta and is important for vascular
development, and consequently has become a compelling target for antiangiogenic
therapies. A few recent studies in gastrointestinal stromal tumor (GIST), breast
cancer, and ovarian cancer, however, suggest that endoglin is upregulated in
tumor cells and is associated with poor prognosis. These findings indicate a
broader role of endoglin in tumor biology, beyond angiogenic effects. The goal of
our current study is to evaluate the effects of targeting endoglin in pancreatic
cancer both in vitro and in vivo. We analyzed the antiproliferative effect of
both RNAi-based and peptide ligand-based inhibition of endoglin in pancreatic
cancer cell lines, the latter yielding a GIPC PDZ domain-targeting lipopeptide
with notable antiproliferative activity. We further demonstrated that endoglin
inhibition induced a differentiation phenotype in the pancreatic cancer cells and
sensitized them against conventional chemotherapeutic drug gemcitabine. Most
importantly, we have demonstrated the antitumor effect of both RNAi-based and
competitive inhibitor-based blocking of endoglin in pancreatic cancer xenograft
models in vivo. To our knowledge, this is the first report exploring the effect
of targeting endoglin in pancreatic cancer cells.
PMID- 25125678
TI - Monotherapy versus combination therapy for sepsis due to multidrug-resistant
Acinetobacter baumannii: analysis of a multicentre prospective cohort--authors'
response.
PMID- 25125679
TI - Improvement in bone mineral density after switching from tenofovir to abacavir in
HIV-1-infected patients with low bone mineral density: two-centre randomized
pilot study (OsteoTDF study).
AB - BACKGROUND: Tenofovir has been associated with a decrease in bone mineral density
(BMD). However, data on changes in BMD after discontinuing tenofovir are lacking.
METHODS: We performed a two-centre randomized pilot study in virologically
suppressed HIV-infected patients receiving tenofovir with osteopenia/osteoporosis
(OsteoTDF study, ClinicalTrials.gov number NCT 01153217). Fifty-four patients
were randomly assigned to switch from tenofovir to abacavir (n = 26) or to
continue with tenofovir (n = 28). Changes in lumbar and total hip BMD were
evaluated at Week 48 from baseline. RESULTS: Five patients discontinued the study
(three from the tenofovir group and two from the abacavir group). No significant
differences were detected between the groups at Week 48 (P = 0.229 for total hip
and P = 0.312 for lumbar spine). However, hip BMD improved by 2.1% (95% CI -0.6
to 4.7) (P = 0.043) in the abacavir group and 0.7% (95% CI -0.9 to 2.4) (P =
0.372) in the tenofovir group. Lumbar spine BMD varied by -0.7% (95% CI -3.8 to
3.3) (P <= 0.001) in the abacavir group and -1.2% (95% CI -3.8 to 0.4) (P <
0.001) in the tenofovir group. CONCLUSIONS: Switching from tenofovir to abacavir
led to a slight improvement in femoral BMD although no differences were detected
between groups. Larger studies are necessary before firm recommendations can be
made on the discontinuation of tenofovir in patients with a low BMD.
PMID- 25125682
TI - NSAID use reduces breast cancer recurrence in overweight and obese women: role of
prostaglandin-aromatase interactions.
AB - Obesity is associated with a worse breast cancer prognosis and elevated levels of
inflammation, including greater cyclooxygenase-2 (COX-2) expression and activity
in adipose-infiltrating macrophages. The product of this enzyme, the
proinflammatory eicosanoid prostaglandin E2 (PGE2), stimulates adipose tissue
aromatase expression and subsequent estrogen production, which could promote
breast cancer progression. This study demonstrates that daily use of a
nonsteroidal anti-inflammatory drug (NSAID), which inhibits COX-2 activity, is
associated with reduced estrogen receptor alpha (ERalpha)-positive breast cancer
recurrence in obese and overweight women. Retrospective review of data from
ERalpha-positive patients with an average body mass index of >30 revealed that
NSAID users had a 52% lower recurrence rate and a 28-month delay in time to
recurrence. To examine the mechanisms that may be mediating this effect, we
conducted in vitro studies that utilized sera from obese and normal-weight
patients with breast cancer. Exposure to sera from obese patients stimulated
greater macrophage COX-2 expression and PGE2 production. This was correlated with
enhanced preadipocyte aromatase expression following incubation in conditioned
media (CM) collected from the obese-patient, sera-exposed macrophages, an effect
neutralized by COX-2 inhibition with celecoxib. In addition, CM from
macrophage/preadipocyte cocultures exposed to sera from obese patients stimulated
greater breast cancer cell ERalpha activity, proliferation, and migration
compared with sera from normal-weight patients, and these differences were
eliminated or reduced by the addition of an aromatase inhibitor during CM
generation. Prospective studies designed to examine the clinical benefit of NSAID
use in obese patients with breast cancer are warranted.
PMID- 25125681
TI - AEG-1 regulates retinoid X receptor and inhibits retinoid signaling.
AB - Retinoid X receptor (RXR) regulates key cellular responses such as cell growth
and development, and this regulation is frequently perturbed in various
malignancies, including hepatocellular carcinoma (HCC). However, the molecule(s)
that physically govern this deregulation are mostly unknown. Here, we identified
RXR as an interacting partner of astrocyte-elevated gene-1 (AEG-1)/metadherin
(MTDH), an oncogene upregulated in all cancers. Upon interaction, AEG-1
profoundly inhibited RXR/retinoic acid receptor (RAR)-mediated transcriptional
activation. Consequently, AEG-1 markedly protected HCC and acute myelogenous
leukemia (AML) cells from retinoid- and rexinoid-induced cell death. In
nontumorigenic cells and primary hepatocytes, AEG-1/RXR colocalizes in the
nucleus in which AEG-1 interferes with recruitment of transcriptional
coactivators to RXR, preventing transcription of target genes. In tumor cells and
AEG-1 transgenic hepatocytes, overexpressed AEG-1 entraps RXR in cytoplasm,
precluding its nuclear translocation. In addition, ERK, activated by AEG-1,
phosphorylates RXR that leads to its functional inactivation and attenuation of
ligand-dependent transactivation. In nude mice models, combination of all-trans
retinoic acid (ATRA) and AEG-1 knockdown synergistically inhibited growth of
human HCC xenografts. The present study establishes AEG-1 as a novel homeostatic
regulator of RXR and RXR/RAR that might contribute to hepatocarcinogenesis.
Targeting AEG-1 could sensitize patients with HCC and AML to retinoid- and
rexinoid-based therapeutics.
PMID- 25125683
TI - Targeting EphA3 inhibits cancer growth by disrupting the tumor stromal
microenvironment.
AB - Eph receptor tyrosine kinases are critical for cell-cell communication during
normal and oncogenic tissue patterning and tumor growth. Somatic mutation
profiles of several cancer genomes suggest EphA3 as a tumor suppressor, but its
oncogenic expression pattern and role in tumorigenesis remain largely undefined.
Here, we report unexpected EphA3 overexpression within the microenvironment of a
range of human cancers and mouse tumor xenografts where its activation inhibits
tumor growth. EphA3 is found on mouse bone marrow-derived cells with mesenchymal
and myeloid phenotypes, and activation of EphA3(+)/CD90(+)/Sca1(+)
mesenchymal/stromal cells with an EphA3 agonist leads to cell contraction, cell
cell segregation, and apoptosis. Treatment of mice with an agonistic alpha-EphA3
antibody inhibits tumor growth by severely disrupting the integrity and function
of newly formed tumor stroma and microvasculature. Our data define EphA3 as a
novel target for selective ablation of the tumor microenvironment and demonstrate
the potential of EphA3 agonists for anticancer therapy.
PMID- 25125684
TI - Enteric neural progenitors are more efficient than brain-derived progenitors at
generating neurons in the colon.
AB - Gut motility disorders can result from an absent, damaged, or dysfunctional
enteric nervous system (ENS). Cell therapy is an exciting prospect to treat these
enteric neuropathies and restore gut motility. Previous studies have examined a
variety of sources of stem/progenitor cells, but the ability of different sources
of cells to generate enteric neurons has not been directly compared. It is
important to identify the source of stem/progenitor cells that is best at
colonizing the bowel and generating neurons following transplantation. The aim of
this study was to compare the ability of central nervous system (CNS) progenitors
and ENS progenitors to colonize the colon and differentiate into neurons.
Genetically labeled CNS- and ENS-derived progenitors were cocultured with aneural
explants of embryonic mouse colon for 1 or 2.5 wk to assess their migratory,
proliferative, and differentiation capacities, and survival, in the embryonic gut
environment. Both progenitor cell populations were transplanted in the postnatal
colon of mice in vivo for 4 wk before they were analyzed for migration and
differentiation using immunohistochemistry. ENS-derived progenitors migrated
further than CNS-derived cells in both embryonic and postnatal gut environments.
ENS-derived progenitors also gave rise to more neurons than their CNS-derived
counterparts. Furthermore, neurons derived from ENS progenitors clustered
together in ganglia, whereas CNS-derived neurons were mostly solitary. We
conclude that, within the gut environment, ENS-derived progenitors show superior
migration, proliferation, and neuronal differentiation compared with CNS
progenitors.
PMID- 25125685
TI - Transforming consumer health informatics through a patient work framework:
connecting patients to context.
AB - Designing patient-centered consumer health informatics (CHI) applications
requires understanding and creating alignment with patients' and their family
members' health-related activities, referred to here as 'patient work'. A patient
work approach to CHI draws on medical social science and human factors
engineering models and simultaneously attends to patients, their family members,
activities, and context. A patient work approach extends existing approaches to
CHI design that are responsive to patients' biomedical realities and personal
skills and behaviors. It focuses on the embeddedness of patients' health
management in larger processes and contexts and prioritizes patients'
perspectives on illness management. Future research is required to advance (1)
theories of patient work, (2) methods for assessing patient work, and (3)
techniques for translating knowledge of patient work into CHI application design.
Advancing a patient work approach within CHI is integral to developing and
deploying consumer-facing technologies that are integrated with patients'
everyday lives.
PMID- 25125686
TI - Reducing caregiver stress with internet-based interventions: a systematic review
of open-label and randomized controlled trials.
AB - OBJECTIVE: The high level of stress associated with caring for others with
medical conditions has been recognized for some time. Reducing caregiver stress
can improve caregiver quality of life as well as improve the care they provide to
loved ones. This systematic review assesses the effectiveness of internet-based
interventions to decrease caregiver stress. MATERIALS AND METHODS: A
comprehensive literature search of Ovid MEDLINE (1946-2013), Embase (1988-2013),
PsycINFO (1987-2013), and CINAHL was conducted using terms related to caregiver
and internet-based interventions. Internet-based interventions involving informal
caregivers in an open-label or randomized controlled trial setting were included.
A pair of raters independently reviewed all published abstracts. Data regarding
participants, interventions, and outcomes were extracted and, for randomized
trials, methodology quality was also reviewed. RESULTS: Eight open-label trials
met the review criteria: three showed positive benefit in reducing caregiver
stress, four were partially positive (some outcomes positive, others negative),
and one was a negative study. Sixteen randomized trials met the review criteria:
six showed positive benefit, five were partially positive, and five were
negative. There were no clear patterns as to the variables (such as study
duration and complexity of intervention) associated with better outcomes,
although earlier studies typically had more negative outcomes. DISCUSSION:
Internet-based interventions were mostly effective in reducing aspects of
caregiver stress and improving their well-being. Further studies to assess
outcomes for caregivers and their recipients' health, different technology
delivery methods, and the cost of such interventions are needed.
PMID- 25125687
TI - Registration of whole immunohistochemical slide images: an efficient way to
characterize biomarker colocalization.
AB - BACKGROUND AND OBJECTIVE: Extracting accurate information from complex biological
processes involved in diseases, such as cancers, requires the simultaneous
targeting of multiple proteins and locating their respective expression in tissue
samples. This information can be collected by imaging and registering adjacent
sections from the same tissue sample and stained by immunohistochemistry (IHC).
Registration accuracy should be on the scale of a few cells to enable protein
colocalization to be assessed. METHODS: We propose a simple and efficient method
based on the open-source elastix framework to register virtual slides of adjacent
sections from the same tissue sample. We characterize registration accuracies for
different types of tissue and IHC staining. RESULTS: Our results indicate that
this technique is suitable for the evaluation of the colocalization of biomarkers
on the scale of a few cells. We also show that using this technique in
conjunction with a sequential IHC labeling and erasing technique offers improved
registration accuracies. DISCUSSION: Brightfield IHC enables to address the
problem of large series of tissue samples, which are usually required in clinical
research. However, this approach, which is simple at the tissue processing level,
requires challenging image analysis processes, such as accurate registration, to
view and extract the protein colocalization information. CONCLUSIONS: The method
proposed in this work enables accurate registration (on the scale of a few cells)
of virtual slides of adjacent tissue sections on which the expression of
different proteins is evidenced by standard IHC. Furthermore, combining our
method with a sequential labeling and erasing technique enables cell-scale
colocalization.
PMID- 25125688
TI - Effects of computer-aided clinical decision support systems in improving
antibiotic prescribing by primary care providers: a systematic review.
AB - OBJECTIVE: To assess the effectiveness of computer-aided clinical decision
support systems (CDSS) in improving antibiotic prescribing in primary care.
METHODS: A literature search utilizing Medline (via PubMed) and Embase (via
Embase) was conducted up to November 2013. Randomized controlled trials (RCTs)
and cluster randomized trials (CRTs) that evaluated the effects of CDSS aiming at
improving antibiotic prescribing practice in an ambulatory primary care setting
were included for review. Two investigators independently extracted data about
study design and quality, participant characteristics, interventions, and
outcomes. RESULTS: Seven studies (4 CRTs, 3 RCTs) met our inclusion criteria. All
studies were performed in the USA. Proportions of eligible patient visits that
triggered CDSS use varied substantially between intervention arms of studies
(range 2.8-62.8%). Five out of seven trials showed marginal to moderate
statistically significant effects of CDSS in improving antibiotic prescribing
behavior. CDSS that automatically provided decision support were more likely to
improve prescribing practice in contrast to systems that had to be actively
initiated by healthcare providers. CONCLUSIONS: CDSS show promising effectiveness
in improving antibiotic prescribing behavior in primary care. Magnitude of
effects compared to no intervention, appeared to be similar to other moderately
effective single interventions directed at primary care providers. Additional
research is warranted to determine CDSS characteristics crucial to triggering
high adoption by providers as a perquisite of clinically relevant improvement of
antibiotic prescribing.
PMID- 25125689
TI - Cross-sectional comparison of coronary artery calcium scores between Caucasian
men in the United States and Japanese men in Japan: the multi-ethnic study of
atherosclerosis and the Shiga epidemiological study of subclinical
atherosclerosis.
AB - The incidence of coronary heart disease in the United States has declined, and
prevalences of several coronary disease risk factors have become comparable to
those in Japan. Therefore, the burden of coronary atherosclerosis may be closer
among younger persons in the 2 countries. We aimed to compare prevalences of
coronary atherosclerosis, measured with coronary artery calcium scores, between
men in the 2 countries by age group (45-54, 55-64, or 65-74 years). We used
community-based samples of Caucasian men in the United States (2000-2002; n =
1,067) and Japanese men in Japan (2006-2008; n = 832) aged 45-74 years,
stratifying them into groups with 0, 1, 2, or >=3 of the following risk factors:
current smoking, overweight, diabetes, dyslipidemia, and hypertension. We
calculated adjusted odds ratios of US Caucasian men's having Agatston scores of
>=10, >=100, and >=400 with reference to Japanese men. Overall, the odds of
Caucasian men having each Agatston cutoff point were greater. The ethnic
difference, however, became smaller in younger age groups. For example, adjusted
odds ratios for Caucasian men's having an Agatston score of >=100 were 2.05,
2.43, and 3.86 among those aged 45-54, 55-64, and 65-74 years, respectively.
Caucasian men in the United States had a higher burden of coronary
atherosclerosis than Japanese men, but the ethnic difference was smaller in
younger age groups.
PMID- 25125690
TI - Validation of self-reported smokeless tobacco use by measurement of serum
cotinine concentration among US adults.
AB - Although investigators have assessed the relationship between self-reported
cigarette smoking and biomarker levels, the validity of self-reported information
on smokeless tobacco (SLT) use is uncertain. We used aggregated data from the
2003-2004, 2005-2006, 2007-2008, and 2009-2010 administrations of the National
Health and Nutrition Examination Survey (NHANES) to compare self-reported SLT use
with serum concentrations of cotinine, a metabolite of nicotine, among US adults
aged >=18 years. Receiver operating characteristic analysis was used to determine
the optimal serum cotinine cutpoint for discriminating SLT users from nonusers of
tobacco, and concordance analysis was used to compare self-reported SLT use with
cotinine levels. Among the 30,298 adult respondents who completed the NHANES
during 2003-2010, 418 reported having exclusively used SLT and no other type of
tobacco (cigarettes, cigars, or pipes) during the past 5 days, while 23,457
reported not using any tobacco. The optimal cotinine cutpoint for discriminating
SLT users from non-tobacco users was 3.0 ng/mL (sensitivity=97.0%,
specificity=93.0%), which was comparable to a revised cutpoint recommended for
identifying adult cigarette smokers. Concordance with cotinine was 96.4% and
93.7% for self-reported SLT use and tobacco nonuse, respectively. These findings
indicate that self-reported SLT use among adults correlates highly with serum
cotinine levels and that the optimal cutpoint for minimizing misclassification of
self-reported use is a serum cotinine concentration of 3.0 ng/mL.
PMID- 25125692
TI - Stress ultrasound evaluation of medial elbow instability in a cadaveric model.
AB - BACKGROUND: An injury of the ulnar collateral ligament (UCL) is potentially
career threatening for elite overhead-throwing athletes. Stress ultrasonography
(SUS) allows for a rapid, cost-effective, and noninvasive evaluation of the UCL
and elbow joint both at rest and with applied stress. PURPOSE/HYPOTHESIS: To
determine the amount of cadaveric elbow valgus gapping with sequential sectioning
of medial elbow structures as measured by SUS. It was hypothesized that the
greatest increase in ulnohumeral joint gapping would be noted with release of the
anterior bundle of the UCL. STUDY DESIGN: Descriptive laboratory study. METHODS:
Twelve cadaveric elbows were divided into 2 groups and dissected in reverse
sequences under the direct supervision of an experienced orthopaedic surgeon.
Baseline ultrasound and SUS with applied valgus loads were performed by an
experienced radiologist. A valgus load was applied at each sectioning interval
using a standardized device. Ulnohumeral joint gapping in millimeters was
measured by SUS for each step as the width of the medial joint from the trochlea
to the sublime tubercle. The mean increases in joint gapping (Delta) between each
step were calculated to quantify the additional gapping achieved with release of
each sequential stabilizer. RESULTS: Release of the anterior band of the anterior
bundle resulted in a mean Delta of 2.0 mm (95% CI, 1.1-2.8 mm). Release of the
posterior band of the anterior bundle resulted in a mean Delta of 1.4 mm (95% CI,
0.6-2.2 mm). Release of the entire anterior bundle caused a mean increase in
ulnohumeral valgus joint gapping of 3.4 mm (95% CI, 2.4-4.3 mm). Release of the
remaining individual structures each resulted in a mean increase in valgus joint
gapping of <=0.8 mm. CONCLUSION: The results of the current cadaveric study
suggest that different amounts of gapping are seen on SUS with sectioning of the
medial elbow stabilizers. The hypothesis was confirmed with release of the
anterior bundle of the UCL resulting in the greatest increase in joint gapping as
measured by SUS. CLINICAL RELEVANCE: This study illustrates that SUS can identify
the contributions of each anatomic portion of the UCL and the flexor-pronator
mass to ulnohumeral joint stability in a cadaveric model.
PMID- 25125693
TI - Cost-effectiveness analyses in orthopaedic sports medicine: a systematic review.
AB - BACKGROUND: As increasing attention is paid to the cost of health care delivered
in the United States (US), cost-effectiveness analyses (CEAs) are gaining in
popularity. Reviews of the CEA literature have been performed in other areas of
medicine, including some subspecialties within orthopaedics. Demonstrating the
value of medical procedures is of utmost importance, yet very little is known
about the overall quality and findings of CEAs in sports medicine. PURPOSE: To
identify and summarize CEA studies in orthopaedic sports medicine and to grade
the quality of the available literature. STUDY DESIGN: Systematic review.
METHODS: A systematic review of the literature was performed to compile findings
and grade the methodological quality of US-based CEA studies in sports medicine.
The Quality of Health Economic Studies (QHES) instrument and the checklist by the
US Panel on Cost-effectiveness in Health and Medicine were used to assess study
quality. One-sided Fisher exact testing was performed to analyze the predictors
of high-quality CEAs. RESULTS: Twelve studies met inclusion criteria. Five
studies examined anterior cruciate ligament reconstruction, 3 studies examined
rotator cuff repair, 2 examined autologous chondrocyte implantation, 1 study
examined hip arthroscopic surgery, and 1 study examined the operative management
of shoulder dislocations. Based on study findings, operative intervention in
sports medicine is highly cost-effective. The quality of published evidence is
good, with a mean quality score of 81.8 (range, 70-94). There is a trend toward
higher quality in more recent publications. No significant predictor of high
quality evidence was found. CONCLUSION: The CEA literature in sports medicine is
good; however, there is a paucity of studies, and the available evidence is
focused on a few procedures. More work needs to be conducted to quantify the cost
effectiveness of different techniques and procedures within sports medicine. The
QHES tool may be useful for the evaluation of future CEAs.
PMID- 25125694
TI - Drug selection and dosing in pregnant cancer patients: insights from clinical
pharmacokinetics.
PMID- 25125691
TI - Marginal structural models in occupational epidemiology: application in a study
of ischemic heart disease incidence and PM2.5 in the US aluminum industry.
AB - Marginal structural models (MSMs) and inverse probability weighting can be used
to estimate risk in a cohort of active workers if there is a time-varying
confounder (e.g., health status) affected by prior exposure-a feature of the
healthy worker survivor effect. We applied Cox MSMs in a study of incident
ischemic heart disease and exposure to particulate matter with aerodynamic
diameter of 2.5 MUm or less (PM2.5) in a cohort of 12,949 actively employed
aluminum workers in the United States. The cohort was stratified by work process
into workers in smelting facilities, herein referred to as "smelters" and workers
in fabrication facilities, herein referred to as "fabricators." The outcome was
assessed by using medical claims data from 1998 to 2012. A composite risk score
based on insurance claims was treated as a time-varying measure of health status.
Binary PM2.5 exposure was defined by the 10th-percentile cutoff for each work
process. Health status was associated with past exposure and predicted the
outcome and subsequent exposure in smelters but not in fabricators. In smelters,
the Cox MSM hazard ratio comparing those always exposed above the cutoff with
those always exposed below the cutoff was 1.98 (95% confidence interval: 1.18,
3.32). In fabricators, the hazard ratio from a traditional Cox model was 1.34
(95% confidence interval: 0.98, 1.83). Results suggest that occupational PM2.5
exposure increases the risk of incident ischemic heart disease in workers in both
aluminum smelting and fabrication facilities.
PMID- 25125696
TI - Evaluation of blood perfusion by laser speckle contrast analysis in different
areas of hands and face in patients with systemic sclerosis.
PMID- 25125697
TI - Phytic acid in green leaves of herbaceous plants-temporal variation in situ and
response to different nitrogen/phosphorus fertilizing regimes.
AB - Phytic acid is the major storage compound for phosphorus (P) in plants. While
accounting for up to 90 % in many seeds, usually only <10 % of total P is found
in phytic acid in green leaves. This study follows up on the findings of a recent
review of the occurrence of phytic acid in green leaves which revealed that (i)
the current knowledge of phytic acid in leaves is mostly based on data from
(fertilized) crop plants and (ii) the proportion of total P in phytic acid seems
to decrease with improved P status in leaves in contrast to an increase in seeds
and fruit. We studied five species of wild herbaceous plants in the field and
under controlled conditions. Foliar P concentrations were much lower than those
of the crops of earlier studies, but the proportion of P in phytic acid was
similar, with little variation during the observation period. Both the field data
and the experimental data showed a statistically indistinguishable negative
correlation of phytic acid-P/total P and total P. In contrast to our expectation,
this negative relationship was not related to differences in relative growth
rates. We conclude that (i) our data of phytic acid concentrations in leaves of
wild plants are in line with earlier observations on crops, and (ii) the trend
towards lower proportions of phytic acid-P with increasing P status is probably a
general phenomenon. Currently lacking a convincing explanation for the second
observation, the role of phytic acid in foliar P metabolism is still unclear.
PMID- 25125695
TI - FHL2 regulates the resolution of tissue damage in chronic inflammatory arthritis.
AB - OBJECTIVE: We analysed the role of the adaptor molecule four-and-a-half Lin11,
Isl-1 & Mec-3 (LIM) domain protein 2 (FHL2) in the activation of fibroblast-like
synoviocytes in human rheumatoid arthritis (RA) and tumour necrosis factor alpha
(TNFalpha)-dependent animal models of the disease. METHODS: Synovial tissues of
patients with RA and osteoarthritis (OA) as well as hind paw sections from
arthritic human TNFalpha transgenic (hTNFtg) mice and synovial fibroblasts from
these were analysed. The effects of cytokines on the expression of FHL2 and
disease-relevant matrixmetalloproteases (MMPs) were determined. Analyses of human
tissue specimens from patients treated with anti-TNFalpha as well as anti
TNFalpha treatment of hTNFtg mice were performed to substantiate the TNFalpha
effects on FHL2 levels. FHL2(-/-) mice and hTNFtg mice (with constitutive or
inducible transgene expression) were crossbred to generate TNFalpha
overexpressing FHL2-deficient animals. Signalling pathways were analysed in cells
from these mice and in human cells after knock down of FHL2 by western blot.
RESULTS: FHL2 levels were higher in RA than in OA and in hTNFtg than in wild-type
mice. Surprisingly, while transforming growth factor (TGF)beta-induced FHL2
expression, TNFalpha suppressed FHL2. In vivo, anti-TNFalpha treatment led to
higher FHL2 levels both in RA patients and hTNFtg mice. The loss of FHL2
increased joint destruction in hTNFtg mice, which was accompanied by elevated MMP
13. In vitro, TNFalpha-mediated MMP-13 was significantly higher in FHL2(-/-)
cells and after knock down of FHL2, which was caused by prolonged p38 MAPK
activation. CONCLUSIONS: These data suggest that FHL2 serves as a protective
factor and that, rather than promoting the pathology, the upregulation of FHL2 in
RA occurs in frame of a regenerative attempt.
PMID- 25125699
TI - Adult Child Migration and the Health of Elderly Parents Left Behind in Mexico.
PMID- 25125698
TI - Manipulating the antioxidant capacity of halophytes to increase their cultural
and economic value through saline cultivation.
AB - Halophytes, salt-tolerant plants, are a source of valuable secondary metabolites
with potential economic value. The steady-state pools of many stress-related
metabolites are already enhanced in halophytes when compared with glycophytes,
but growth under conditions away from the optimum can induce stress and
consequently result in changes to secondary metabolites such as antioxidants.
However, direct evidence for increasing the concentration of valuable secondary
metabolites as a consequence of altering the salinity of the growing environment
still remains equivocal. To address this, we analysed a range of metabolites with
antioxidant capacity (including total phenols, flavonoids, ascorbate,
reduced/oxidized glutathione and reactive oxygen species scavenging enzymes) in
seedlings and plants from different families (Amaranthaceae, Brassicaceae,
Plantaginaceae and Rhizophoraceae) and habitats grown under different salt
concentrations. We show that it is possible to manipulate the antioxidant
capacity of plants and seedlings by altering the saline growing environment, the
length of time under saline cultivation and the developmental stage. Among the
species studied, the halophytes Tripolium pannonicum, Plantago coronopus,
Lepidium latifolium and Salicornia europaea demonstrated the most potential as
functional foods or nutraceuticals.
PMID- 25125700
TI - What Goes Up Must Come Down? Experimental Evidence on Intuitive Forecasting.
AB - Do laboratory subjects correctly perceive the dynamics of a mean-reverting time
series? In our experiment, subjects receive historical data and make forecasts at
different horizons. The time series process that we use features short-run
momentum and long-run partial mean reversion. Half of the subjects see a version
of this process in which the momentum and partial mean reversion unfold over 10
periods ('fast'), while the other subjects see a version with dynamics that
unfold over 50 periods ('slow'). Typical subjects recognize most of the mean
reversion of the fast process and none of the mean reversion of the slow process.
PMID- 25125701
TI - Electrical interactions in the cell: Asymmetric screening in a watery antiverse.
AB - The problem of electrostatics in biomolecular systems presents an excellent
opportunity for cross-disciplinary science and a context in which fundamental
physics is called for to answer complex questions. Due to the large density in
biological cells of charged biomacromolecules such as protein factors and DNA, it
is challenging to understand quantitatively the electric forces in these systems.
Two questions are especially puzzling. First, how is it that such a dense system
of charged molecules does not simply aggregate in random and non-functional ways?
Second, since some mechanism apparently prevents such aggregation, how is it that
binding of biomolecules still occurs so reliably? Recognizing the role of water
as a universal solvent in living systems is key to understanding these questions.
We present a simplified physical model in which water is regarded as a medium of
high dielectric constant that nevertheless exhibits the key features essential
for answering the two questions presented. The answer to the first question lies
in the strong screening ability of water, which reduces the energy scale of the
electrostatic interactions. Furthermore, our model reveals the existence of
asymmetric screening, a pronounced asymmetry between the screening for a system
with like charges and that for a system with opposite charges, and this provides
an answer to the second question.
PMID- 25125702
TI - An AFM Study of the Effects of Silanization Temperature, Hydration, and Annealing
on the Nucleation and Aggregation of Condensed OTS Domains on Mica.
AB - Partial monolayers of octadecyltrichlorosilane (OTS) were formed on mica under
different reaction conditions in which the silanization temperature, time, and
amount of water adsorbed on the mica substrates were varied. OTS surface coverage
increased with silanization time for all samples; however, the amount and
distribution of adsorbed OTS varied greatly under these different reaction
conditions. AFM analysis showed that OTS formed two phases on mica silanized at
25 degrees C: condensed "island-like" domains and expanded "liquid-like" domains.
Partially dehydrated mica silanized at 9 degrees C, however, displayed only
condensed domains which were of smaller size compared to those on the 25 degrees
C samples. The lateral diffusion and aggregation of small condensed OTS domains
to form larger aggregates was evident on all surfaces except the 25 degrees C
partially dehydrated mica. A uniform distribution of many small condensed domains
surrounded by expanded OTS phases was seen instead. Extended annealing resulted
in surface diffusion and aggregation of these domains and nucleation of new
condensed domains from the surrounding expanded OTS phases. These observations
are consistent with a deposition, diffusion, and aggregation model (DDA) which
allows for activated diffusion; however, rigorous modeling is not presented here.
PMID- 25125703
TI - Parents' Relationship Quality and Children's Behavior in Stable Married and
Cohabiting Families.
AB - Although an extensive literature has shown that family structure is linked with
child well-being, less well understood is how the dynamics within families affect
children, in particular the extent to which positive mother-father relationship
quality is linked with children's outcomes. In this study the authors used data
from the Fragile Families and Child Wellbeing Study (N = 773) to examine how
couple supportiveness in stable coresident families is related to children's
externalizing and internalizing behavioral problems over ages 3 through 9. Using
latent growth curve and fixed effects models, they found that parents' greater
supportiveness has a slight association with lower levels of children's
behavioral problems. Using cross-lagged structural equation models to examine the
direction of the association, they also found some evidence that parents'
relationship quality and children's behavioral problems are reciprocally related.
Overall, this study suggests that more positive couple interactions are
beneficial for children residing with both of their biological parents.
PMID- 25125704
TI - Single Motherhood, Living Arrangements, and Time With Children in Japan.
AB - The authors examined relationships between single parenthood and mothers' time
with children in Japan. Using data from the 2011 National Survey of Households
with Children (N = 1,926), they first demonstrate that time spent with children
and the frequency of shared dinners are significantly lower for single mothers
than for their married counterparts. For single mothers living alone, less time
with children reflects long work hours and work-related stress. Single mothers
coresiding with parents spend less time with children and eat dinner together
less frequently than either married mothers or their unmarried counterparts not
living with parents, net of (grand)parental support, work hours, income, and
stress. The findings suggest that rising divorce rates and associated growth in
single-mother families may have a detrimental impact on parents' time with
children in Japan and that the relatively high prevalence of intergenerational
coresidence among single mothers may do little to temper this impact.
PMID- 25125705
TI - Predictors of Self-reported Sexually Transmitted Diseases among Homeless and
Runaway Adolescents.
AB - Path analysis was used to investigate factors associated with self-reported
sexually transmitted diseases among 569 homeless and runaway adolescents in four
Midwestern states. Youth were interviewed by outreach workers directly on the
streets, in shelters, and in drop-in centers. Results indicated that family abuse
was positively related to substance use, affiliation with friends who sold sex,
and time on own. Early family abuse indirectly increased the likelihood of self
reported sexually transmitted diseases through time on own, substance use,
friends selling sex, and risky sexual behaviors. Finally, substance use and
affiliation with friends who sold sex was positively associated with risky sexual
behaviors, which in turn was related to self-reported sexually transmitted
diseases. No significant gender interactions were found for this model.
PMID- 25125706
TI - Weighted Area Under the Receiver Operating Characteristic Curve and Its
Application to Gene Selection.
AB - Partial area under the ROC curve (PAUC) has been proposed for gene selection in
Pepe et al. (2003) and thereafter applied in real data analysis. It was noticed
from empirical studies that this measure has several key weaknesses, such as an
inability to reflect nonuniform weighting of different decision thresholds,
resulting in large numbers of ties. We propose the weighted area under the ROC
curve (WAUC) in this paper to address the problems associated with PAUC. Our
proposed measure enjoys a greater flexibility to describe the discrimination
accuracy of genes. Nonparametric and parametric estimation methods are
introduced, including PAUC as a special case, along with theoretical properties
of the estimators. We also provide a simple variance formula, yielding a novel
variance estimator for nonparametric estimation of PAUC, which has proven
challenging in previous work. The proposed methods permit sensitivity analyses,
whereby the impact of differing weight functions on gene rankings may be assessed
and results may be synthesized across weights. Simulations and re-analysis of two
well-known microarray datasets illustrate the practical utility of WAUC.
PMID- 25125707
TI - Children in Institutional Care: Delayed Development and Resilience.
AB - Children exposed to institutional care often suffer from "structural neglect"
which may include minimum physical resources, unfavorable and unstable staffing
patterns, and social-emotionally inadequate caregiver-child interactions. This
chapter is devoted to the analysis of the ill effects of early institutional
experiences on resident children's development. Delays in the important areas of
physical, hormonal, cognitive, and emotional development are discussed. The
evidence for and against the existence of a distinctive set of co-occurring
developmental problems in institutionalized children is weighed and found to not
yet convincingly demonstrate a "post-institutional syndrome". Finally, shared and
non-shared features of the institutional environment and specific genetic,
temperamental, and physical characteristics of the individual child are examined
that might make a crucial difference in whether early institutional rearing
leaves irreversible scars.
PMID- 25125708
TI - Sensitive Periods.
AB - This chapter reviews sensitive periods in human brain development based on the
literature on children raised in institutions. Sensitive experiences occur when
experiences are uniquely influential for the development of neural circuitry.
Because in humans, we make inferences about sensitive periods from evaluations of
complex behaviors, we underestimate the occurrence of sensitive periods at the
level of neural circuitry. Although we are most interested in complex behaviors,
such as IQ or attachment or externalizing problems, many different sensitive
periods at the level of circuits probably underlie these complex behaviors.
Results from a number of studies suggest that across most, but not all, domains
of development, institutional rearing limited to the first 4-6 months of life is
associated with no significant increase risk for long-term adverse effects
relative to non-institutionalized children. Beyond that, evidence for sensitive
periods is less compelling, meaning that "the earlier the better" rule for
enhanced caregiving is a reasonable conclusion at the current state of the
science.
PMID- 25125709
TI - Tetrasubstituted pyrazinones derived from the reaction of praziquantel with N
bromosuccinimide.
AB - When praziquantel was exposed to N-bromosuccinimide in the presence of ethanol, a
tricyclic 3-bromo-1-ethoxy pyrazinone was formed. From this and the analogous 1,3
dibromopyrazinone, a small library of 3-alkylamino-1-ethoxy, 1,3-dialkoxy, 3
alkoxy-1-bromo, and 3-alkylamino-1-bromo substituted pyrazinones were synthesized
in high yields.
PMID- 25125710
TI - Enantioselective synthesis of decalin structures with all-carbon quaternary
centers via one-pot sequential Cope/Rauhut-Currier reaction.
AB - The first example of one-pot sequential Cope/Rauhut-Currier reactions are
reported and used to make functionalized decalin structures with all-carbon
quaternary stereocenters. The substrates for the new sequential reaction are
generated through a six-step sequence including an enantioselective Birch
reduction-allylation reaction which makes the overall process asymmetric.
PMID- 25125711
TI - Varying coefficient subdistribution regression for left-truncated semi-competing
risks data.
AB - Semi-competing risks data frequently arise in biomedical studies when time to a
disease landmark event is subject to dependent censoring by death, the
observation of which however is not precluded by the occurrence of the landmark
event. In observational studies, the analysis of such data can be further
complicated by left truncation. In this work, we study a varying co-efficient
subdistribution regression model for left-truncated semi-competing risks data.
Our method appropriately accounts for the specifical truncation and censoring
features of the data, and moreover has the flexibility to accommodate potentially
varying covariate effects. The proposed method can be easily implemented and the
resulting estimators are shown to have nice asymptotic properties. We also
present inference, such as Kolmogorov-Smirnov type and Cramer Von-Mises type
hypothesis testing procedures for the covariate effects. Simulation studies and
an application to the Denmark diabetes registry demonstrate good finite-sample
performance and practical utility of the proposed method.
PMID- 25125712
TI - Nativity Differences in Youths' Weight Trajectories: Foreign-Born Health
Integration during the Transition to Adulthood.
AB - Nativity differences in youths' health in the United States are striking, with
the children of foreign-born parents showing more favorable outcomes than those
of native-born parents. Very little is known about how inequalities evolve within
the same individuals over time, or more generally about life cycle aspects of the
health integration of youth with migration backgrounds. Using data from the
National Longitudinal Study of Adolescent Health, I examine nativity differences
in trajectories of weight gain during adolescence and early adulthood, as well as
the degree to which trajectories are stratified by race/ethnicity and
socioeconomic status. Do nativity differences converge, diverge or remain stable
over time, and how are patterns socially stratified within and across nativity
groups? I find that first-generation adolescents begin at a lower weight than
their third generation peers and gain weight at a significantly slower pace,
producing meaningful differences by early adulthood. More complex examination of
the relationship between nativity and weight gain reveals additional differences
by ethnicity: the foreign-born advantage over time does not extend as strongly to
Hispanic adolescents. The findings demonstrate how the health-related integration
of foreign-born youth is tied to race/ethnicity and socioeconomic circumstances,
and suggest the need to examine the ways in which social circumstances and health
change together.
PMID- 25125713
TI - Neighborhood Characteristics, Parental Practices and Children's Math Achievement
in Elementary School.
AB - : This paper investigates the relationships among neighborhood characteristics,
education-related parental practices, and children's academic achievement during
a critical but under-studied stage of children's educational trajectories - the
elementary school years. Using a large, nationally representative database of
American elementary school students - the Early Childhood Longitudinal Study -
Kindergarten Cohort (ECLS-K) - and contextual data from the 2000 U.S. Census, we
examine parental practices and neighborhood characteristics at the beginning of
children's school careers (grades K-1) and their associations with math
achievement through the end of the 5th grade. FINDINGS: Net of family-level
characteristics, higher levels of early education- oriented parental practices
were associated with higher mathematics achievement at the end of 5th grade,
while neighborhood disadvantage was associated with lower 5th grade math
achievement. Families residing in high poverty, high unemployment, low-education
neighborhoods employed fewer education- oriented practices with their
kindergarten- first grade children, but the positive effect of such parental
practices on children's mathematics achievement was stronger for children who
live in disadvantaged neighborhoods.
PMID- 25125714
TI - President's address: Mary Shelley, Frankenstein, and the dark side of medical
science.
PMID- 25125715
TI - A novel T cell evasion mechanism in persistent RNA virus infection.
AB - Hepatitis C virus (HCV) and GB virus type C (GBV-C) are associated with impaired
T cell function despite the fact that HCV replicates in hepatocytes and GBV-C in
a small proportion of lymphocytes. Recently, we showed that HCV and GBV-C E2
envelope proteins reduce T cell activation via the T cell receptor (TCR) by
competing for phosphorylation with a critical kinase in the TCR signaling cascade
(Lck). E2 interfered with TCR signaling in E2 expressing cells and in bystander
cells. The bystander effect was mediated by virus particles and extracellular
microvesicular particles (exosomes). Multiple kinase substrate sites are
predicted to reside on viral structural proteins and based on bioinformatic
predictions, many RNA virus pathogens may interfere with TCR signaling via a
similar mechanism. Identification of T cell inhibitory effects of virus
structural proteins may provide novel approaches to enhance the immunogenicity
and memory of viral vaccines.
PMID- 25125717
TI - Scanning the chronic disease terrain: prospects and opportunities.
AB - The disease burden in the United States has changed radically in the past 100
years. A striking decrease in infectious diseases as causes of morbidity and
mortality has been followed by a steady increase in morbidity and mortality rates
from chronic disease, which is now the dominant health issue facing the country,
at levels justifying considering chronic disease as having reached epidemic
proportions. Research in recent years has shown that many of the common chronic
diseases are malleable, i.e., susceptible to therapeutic or preventive efforts
aimed at risk factors and susceptible age eras and populations. Although clinical
and population-oriented interventions have been increasingly successful in recent
decades, more intensive and coordinated preventive efforts will be required,
including effective partnerships between clinical medicine and other sectors,
particularly at-risk individuals, government, and public health. Robust joint
efforts are not only needed, but are likely to be successful.
PMID- 25125716
TI - Translational studies in older men using testosterone to treat sarcopenia.
AB - Sarcopenia is the loss of skeletal muscle mass and strength that occurs with
aging. Our research group has found an efficacious administration paradigm using
testosterone to combat sarcopenia in humans. In addition, our research has
uncovered an important regulatory enzyme of inflammation, nuclear factor-kappaB
inducing kinase that may regulate human skeletal muscle catabolism, and that
appears to be counter-regulated by administration of standard doses of
testosterone. This is important because a number of age-related clinical
circumstances trigger acute and chronic muscle loss including cancer, chronic
obstructive pulmonary disease, hospitalization, acute and chronic illness, and
diseases in which systemic inflammation occurs. Moreover, it is often the
treatment itself that can induce muscle loss. For example, glucocorticoids are
tremendously effective at reducing inflammation and are a frontline therapy for
many inflammatory-based diseases, yet paradoxically trigger muscle loss. We will
discuss our research findings and the clinical significance of our human clinical
translational research with testosterone.
PMID- 25125718
TI - "Reverse genomics" and human endogenous retroviruses.
AB - Over millions of years, actively replicating retroviruses entered the human
genome and through time became a stable and substantial part of the inherited
genetic material. A remarkable 8% of the human genome is accounted for by
endogenous retroviruses, whose biological importance has not yet been elucidated.
In studying the RNA of these endogenous retroviruses in the blood of living human
subjects with HIV infection, we have discovered a whole new family of these
viruses that had been hidden in the centromeres of specific human chromosomes.
These retroviruses have specific sequences that can elucidate their chromosome of
origin. As centromeres represent the most substantial remaining frontier of human
genomics, these viral sequences can provide a "bar-code" that can be used to
study the role of centromeres in biology and in disease. This work also
highlights the efficacy of using "reverse genomics" to understand and annotate
the human genome.
PMID- 25125720
TI - The natural history of acute dilated cardiomyopathy.
AB - INTRODUCTION: Acute dilated cardiomyopathy (ADCM) is a frequent cause for
referral for cardiac transplantation yet its prognosis and natural history on
contemporary therapy remain uncertain. METHODS: The Multicenter Intervention in
Myocarditis and Acute Cardiomyopathy (IMAC)-2 trial enrolled 373 patients at 12
academic medical centers with left ventricular ejection fraction (LVEF) <= 40%,
heart failure symptoms < 6 months duration, and a diagnostic evaluation
consistent with idiopathic cardiomyopathy or acute myocarditis. The natural
history of ADCM in an earlier era (1975-2000) was also examined via a MEDLINE
search of published observational studies. RESULTS: Mean age of the IMAC-2 study
cohort was 45 +/- 4 years and 38% were female. Mean initial LVEF was 24% +/- 8%
and increased to 40% +/- 12% during treatment with ACE-I/ARB (82%), and a beta
blocker (94%). Transplantation-free survival at 1, 2, and 4 years was 94%, 92%,
and 86%, respectively. This survival rate was substantially higher than the prior
era. Multivariate predictors of improvement in LVEF were smaller LV dimension and
higher systolic blood pressure whereas black race and higher initial New York
Heart Association functional class were associated with lower final LVEF.
Genotypic variation did not correlate with response to pharmacological therapy.
CONCLUSION: Earlier diagnosis and aggressive pharmacologic and device-based
therapy of ADCM has led to improved prognosis.
PMID- 25125719
TI - Bitter taste receptors in the wrong place: novel airway smooth muscle targets for
treating asthma.
AB - There is a need to expand the classes of drugs used to treat obstructive lung
diseases to achieve better outcomes. With only one class of direct
bronchodilators (beta-agonists), we sought to find receptors on human airway
smooth muscle (ASM) that act via a unique mechanism to relax the muscle, have a
diverse agonist binding profile to enhance the probability of finding new
therapeutics, and relax ASM with equal or greater efficacy than beta-agonists. We
have found that human and mouse ASM express six bitter taste receptor (TAS2R)
subtypes, previously thought only to exist in taste buds of the tongue. Agonists
acting at TAS2Rs evoke profound bronchodilation via a Ca(2+)-dependent mechanism.
TAS2R function is not altered in asthma models, undergoes minimal tachyphylaxis
upon repetitive dosing, and relaxes even under extreme desensitization of
relaxation by beta-agonists. Taken together, TAS2Rs on ASM represent a novel
pathway to consider for development of agonists in the treatment of asthma and
chronic obstructive lung disease.
PMID- 25125721
TI - Teaching evidence-based medicine in the former Soviet Union: lessons learned.
AB - Between 2009 and 2012, I taught principles of evidence-based medicine and
clinical research in Russia, Tatarstan, Moldova, and Kazakhstan. The Soviet Union
left a medical legacy characterized by balkanization of top tier medicine in
highly specialized centers, so there was little capability for multidiscipinary
care. In addition, the authoritarian government led to a persistently top-down
tradition of medical education and practice, which one of my Russian colleagues
aptly named "eminence-based medicine." After the fall of the Soviet Union,
funding for science and medical research was drastically cut, leading to a
struggle for resources and politicization of resource decisions. At present,
prejudices and beliefs about disease and treatment persist untested, limited
English language competency impedes acquisition of new knowledge, and restriction
of resources cripples innovation. Yet none of these conditions are unknown to us
in the United States. Physicians may resist evidence that challenges long-held
beliefs, and patients want us to make decisions based on their individual case,
not evidence arising from studying other people. As physicians, we need to
understand how to communicate with and frame our arguments so that they can be
understood and received favorably. Can we draw lessons from trying to teach
evidence-based medicine in the former Soviet Union?
PMID- 25125724
TI - Gordon Wilson lecture: opening doors worldwide through medical science: personal
reflections.
PMID- 25125725
TI - Curing genetic disease with gene therapy.
AB - Development of viral vectors that allow high efficiency gene transfer into
mammalian cells in the early 1980s foresaw the treatment of severe monogenic
diseases in humans. The application of gene transfer using viral vectors has been
successful in diseases of the blood and immune systems, albeit with several
curative studies also showing serious adverse events (SAEs). In children with X
linked severe combined immunodeficiency (SCID-X1), chronic granulomatous disease,
and Wiskott-Aldrich syndrome, these SAEs were caused by inappropriate activation
of oncogenes. Subsequent studies have defined the vector sequences responsible
for these transforming events. Members of the Transatlantic Gene Therapy
Consortium [TAGTC] have collaboratively developed new vectors that have proven
safer in preclinical studies and used these vectors in new clinical trials in
SCID-X1. These trials have shown evidence of early efficacy and preliminary
integration analysis data from the SCID-X1 trial suggest an improved safety
profile.
PMID- 25125726
TI - The immune system in hypertension.
AB - Hypertension is generally attributed to perturbations of the vasculature, the
kidney, and the central nervous system. During the past several years, it has
become apparent that cells of the innate and adaptive immune system also
contribute to this disease. Macrophages and T cells accumulate in the kidneys and
vasculature of humans and experimental animals with hypertension, and likely
contribute to end-organ damage. We have shown that mice lacking lymphocytes, such
as recombinase-activating gene-deficient (RAG-1(-/-)) mice, have blunted
hypertension in response to angiotensin II, increased salt levels, and
norepinephrine. Adoptive transfer of T cells restores the blood pressure response
to these stimuli. Others have shown that mice with severe combined
immunodeficiency have blunted hypertension in response to angiotensin II.
Deletion of the RAG gene in Dahl salt-sensitive rats reduces the hypertensive
response to salt feeding. The central nervous system seems to orchestrate immune
cell activation. We produced lesions of the anteroventral third ventricle and
showed that these block T cell activation in response to angiotensin II.
Likewise, we showed that genetic manipulation of reactive oxygen species in the
subfornical organ modulates both hypertension and T cell activation. Current
evidence indicates that production of cytokines including tumor necrosis factor
alpha, interleukin 17, and interleukin 6 contribute to hypertension, likely by
promoting vasoconstriction, production of reactive oxygen species, and sodium
reabsorption in the kidney. We propose a working hypothesis linking the
sympathetic nervous system, immune cells, the production of cytokines, and
ultimately vascular and renal dysfunction, leading to augmentation of
hypertension.
PMID- 25125727
TI - Impact of denervated myocardium on improving risk stratification for sudden
cardiac death.
AB - Between 184,000 and 462,000 Americans die suddenly each year. Fifty percent to
70% of these deaths are due to ventricular tachycardia/fibrillation (VT/VF). We
tested whether hibernating myocardium or myocardial sympathetic denervation
identifies patients at high-risk for developing VT/VF independently of ejection
fraction (EF). Positron emission tomography (PET) was used to quantify myocardial
sympathetic denervation ((11)C-meta-hydroxyephedrine [(11)C-HED]), perfusion
((13)N-ammonia), and viability (insulin-stimulated (18)F-2-deoxyglucose
[(18)FDG]) in patients with ischemic cardiomyopathy (EF < 35%) eligible for a
primary prevention implantable cardioverter defibrillator (ICD). The primary end
point was sudden cardiac arrest (SCA) defined as arrhythmic death or ICD
discharge for VT/VF > 240 bpm. Volumes of total denervated (P = .001) and viable
denervated myocardium ((11)C-HED-(18)FDG mismatch, P = .03) predicted SCA,
whereas hibernating and infarcted myocardium did not. Multivariate analysis
identified four independent predictors of SCA: denervated myocardium > 37.6% of
left ventricule (LV), LV end-diastolic volume > 98 mL/m(2), creatinine level >
1.49 mg/dL, and no angiotensin- inhibition therapy. Denervated myocardium had a
hazard ratio of 3.5 for SCA (10.3%/year vs. 3.0%/year, p=0.001). Absence of all
four factors predicted low risk (44% of cohort; SCA <1%/y) whereas two or more
factors identified subjects at high-risk (20% of cohort; SCA 12%/y). Denervated
myocardium quantified using PET strongly predicts risk of SCA, and is independent
of EF, infarct volume, and other clinical variables.
PMID- 25125728
TI - Back to the beginning for the Eighth Evacuation Hospital in Morocco during World
War II 70 years ago.
PMID- 25125731
TI - Three ways to die suddenly: do they all require calcium calmodulin-dependent
protein kinase II?
AB - Sudden cardiac death occurs due to a limited number of pathological events. The
heart can beat too fast or too slow to maintain adequate cardiac output or the
heart can rupture. Here we survey recent evidence that excessive activation of
calcium calmodulin-dependent protein kinase II by three core neurohumoral
pathways or by oxidant stress can lead to sudden cardiac death due to sinus node
dysfunction and bradycardia, ventricular tachycardia or fibrillation, and cardiac
rupture.
PMID- 25125734
TI - The endemic mimic: blastomycosis an illness often misdiagnosed.
AB - One of the endemic fungi, Blastomyces dermatitidis, can cause epidemics of
infection with multiple persons involved in a point source outbreak but more
commonly causes sporadic cases of infection within the areas of endemicity.
Blastomycosis can present as an acute pneumonia which is often misdiagnosed as
acute pneumococcal pneumonia or the infection may present as a chronic pneumonia
along with weight loss, night sweats, hemoptysis, and a lung mass suggesting
tuberculosis or carcinoma of the lung. Extrapulmonary infection with B.
dermatitidis is protean with many different manifestations. Most commonly, skin
or subcutaneous lesions are found with either a verrucous or warty appearance or
in an ulcerative form. Cases have been misidentified as keratoacanthoma, pyoderma
gangrenosum, carcinoma, or as Weber-Christian panniculitis if there are nodular
subcutaneous lesions. Essentially any site or organ can have lesions of
disseminated blastomycosis. In our series, cases of laryngeal carcinoma, adrenal
insufficiency, thyroid nodules, granulomatous hypercalcemia, abnormal mammograms
thought to represent breast carcinoma, otitis media with cranial extension,
immune thrombocytopenic purpura, and hemolytic anemia of unknown cause have been
misdiagnosed and blastomycosis subsequently identified as the cause. This
infection causes manifestations which mimic many other more commonly diagnosed
conditions and must always be considered by clinicians practicing in the endemic
region.
PMID- 25125735
TI - The role of pragmatic clinical trials in the evolution of learning health
systems.
AB - Pragmatic clinical trials (PCTs) test clinical interventions (eg, treatments,
diagnostic tests, delivery strategies) that are widely used in practice and for
which there is often clinical equipoise. Similar to traditional explanatory
trials of novel therapeutics, PCTs use randomization to decrease selection bias.
In contrast, PCTs rely on extant data sources (eg, electronic medical records
[EMRs]) and test interventions that can be implemented with minimal research
infrastructures. Thus, PCTs have drawn interest as vehicles for decreasing the
cost of clinical research and for creating learning health systems, which, as
articulated by the Institute of Medicine, seek to generate new knowledge as an
integral by-product of the delivery experience. However, realizing this vision
for PCTs will require innovative approaches for engaging clinicians, improving
the efficiency of subject recruitment, improving the reliability of EMR data, and
new paradigms for the regulatory review of low-risk trials to decrease unncessary
hurdles to practice-based knowledge generation.
PMID- 25125736
TI - Quantitative human phenotyping: the next frontier in medicine.
PMID- 25125741
TI - The Bert and Peggy Dupont lecture: prelude to war, a gentlemen's affair: the
story behind the Battle of Fort Sumter, April 1861.
PMID- 25125737
TI - Addressing the global burden of chronic kidney disease through clinical and
translational research.
AB - Worldwide, an estimated 200 million people have chronic kidney disease (CKD). In
the United States, African Americans (AAs) have a four-fold excess risk of CKD
compared to non-Hispanic white people and globally, people in the low-to-middle
income countries of Asia and Sub-Saharan Africa have the highest rates of CKD.
Annually, more than 500,000 individuals develop end-stage renal disease (or CKD
stage 5) in Sub-Saharan Africa alone and the vast majority of these patients
suffer premature mortality. The health care costs and economic burden of CKD are
huge and not sustainable even in advanced Western countries. A recent discovery
on the role of Apolipoprotein 1 (APOL1) G1 and G2 renal risk variants in AAs has
a huge potential to unravel the etiology of CKD in both AA and other black
populations. Under the National Institutes of Health (NIH)-sponsored Human
Heredity and Health in Africa (H3Africa) initiative, a large prospective genetic
study of CKD is being conducted in 8000 participants in four African countries
(Ethiopia, Ghana, Kenya, and Nigeria; for a total population of 320 million).
This and other basic research studies in the United States could potentially shed
great insight into the genetics and biologic mechanisms involved in the excess
predilection of Africans and AAs to CKD.
PMID- 25125744
TI - The Jeremiah Metzger lecture: new additions to the toolbox for global malaria
eradication.
PMID- 25125745
TI - Mechanisms of hypoglycemia and exercise-associated autonomic dysfunction.
AB - It is well established that diabetes can lead to multiple microvascular and
macrovascular complications. Several large scale randomized multicenter studies
have shown that intensifying glucose control decreases microvascular and, to a
certain extent, macrovascular complications of diabetes. However, intensifying
glucose control in both type 1 and type 2 diabetes increases the risk of
developing hypoglycemia, one of the most feared complications of people with the
disease. The mechanisms responsible for intensive therapy causing increased
hypoglycemia in patients with diabetes have been extensively investigated. It is
now known that a single episode of hypoglycemia can blunt the body's normal
counterregulatory defenses against subsequent hypoglycemia or exercise.
Similarly, a single bout of exercise can also blunt counterregulatory responses
against subsequent hypoglycemia. Both neuroendocrine and autonomic nervous system
responses are reduced by prior hypoglycemia and/or exercise. Work from several
laboratories has identified multiple physiologic mechanisms involved in the
pathogenesis of this hypoglycemia and exercise-associated counterregulatory
failure. By continuing to study these mechanisms, some promising approaches to
amplify counterregulatory responses to hypoglycemia are being discovered.
PMID- 25125746
TI - Kidney injury molecule-1: a translational journey.
AB - Kidney injury molecule-1 (KIM-1, also named TIM-1 and HAVCR-1) was identified as
the most highly upregulated protein in the proximal tubule of the kidney after
injury. This protein is present with injury in multiple species including man,
and also after a large number of acute and chronic insults to the kidney. It is a
type-1 membrane protein whose ectodomain is released into the lumen of the
tubule. The ectodomain is heavily glycosylated and stable and appears in the
urine after injury. It has been qualified by the United States Food and Drug
Administration and the European Medicines Agency for preclinical assessment of
nephrotoxicity and on a case-by-case basis for clinical evaluation. As a
biomarker in humans, its utility has been demonstrated in acute and chronic
injury and in renal cell carcinoma, a condition similar to injury, where there is
dedifferentiation of the epithelial cell. KIM-1 is a phosphatidylserine receptor
which recognizes apoptotic cells directing them to lysosomes. It also serves as a
receptor for oxidized lipoproteins and hence is important for uptake of
components of the tubular lumen which may be immunomodulatory and/or toxic to the
cell. KIM-1 is unique in being the first molecule, not also present on myeloid
cells, that transforms kidney proximal epithelial cells into semi-professional
phagocytes. Data suggest that KIM-1 expression is protective during early injury,
whereas in chronic disease states, prolonged KIM-1 expression may be maladaptive
and may represent a target for therapy of chronic kidney disease.
PMID- 25125748
TI - "An aristocracy of talent": the South Carolina physician-naturalists and their
times.
AB - During the natural history movement of the 18th and early 19th centuries,
Charleston as a center was rivaled in the United States only by Philadelphia, New
York, and Boston. Prominent physician-naturalists included Alexander Garden (for
whom the gardenia is named), John Edwards Holbrook ("father of American
herpetology"), and Francis Peyre Porcher (whose Resources of Southern Fields and
Forests helped Confederates compensate for drug shortages). The Charleston
physician-naturalists belonged to an "aristocracy of talent" as distinguished
from the "aristocracy of wealth" of lowcountry planters, who probably did more
than any other group to perpetuate slavery and propel the South toward a
disastrous civil war. None of the physician-naturalists actively opposed slavery
or secession, a reminder that we are all prisoners of the prevailing paradigms
and prejudices of our times.
PMID- 25125747
TI - TGFBR1 and cancer susceptibility.
AB - Transforming growth factor beta (TGF-beta) is a potent inhibitor of cell growth.
TGFBR1 6A is a polymorphism consisting of a 9-base pair in-frame deletion within
exon 1 of the type I TGF-beta receptor (TGFBR1), which results in a receptor with
decreased TGF-beta signaling capability. The discovery of an association between
TGFBR1*6A and cancer susceptibility led to the hypothesis that hypomorphic
variants of the TGF-beta signaling pathway may predispose to the development of
cancer. This hypothesis was tested in vivo with the development of a mouse model
of Tgfbr1 haploinsufficiency. Tgfbr1 (+/-) mice developed twice as many
intestinal tumors as Tgfbr1 (+/+). Tgfbr1 haploinsufficiency was also associated
with early onset adenocarcinoma and increased tumor cell proliferation. A case
control study identified two haplotypes associated with constitutively decreased
TGFBR1 and substantially increased colorectal cancer risk indicating that TGFBR1
may act as a potent modifier of cancer risk.
PMID- 25125749
TI - Can visual arts training improve physician performance?
AB - Clinical educators use medical humanities as a means to improve patient care by
training more self-aware, thoughtful, and collaborative physicians. We present
three examples of integrating fine arts - a subset of medical humanities - into
the preclinical and clinical training as models that can be adapted to other
medical environments to address a wide variety of perceived deficiencies. This
novel teaching method has promise to improve physician skills, but requires
further validation.
PMID- 25125756
TI - Secretary-Treasurer's report: the 126(th) meeting held at The Charleston Place
Hotel Charleston, South Carolina October 17(th) through October 20(th), 2013.
PMID- 25125757
TI - Accountants' compilation report to the board of trustees: American Clinical and
Climatological Association, Baton Rouge, Louisiana.
PMID- 25125750
TI - Using 2-photon microscopy to understand albuminuria.
AB - Intravital 2-photon microscopy, along with the development of fluorescent probes
and innovative software, has rapidly advanced the study of intracellular and
intercellular processes at the organ level. Researchers can quantify the
distribution, behavior, and dynamic interactions of up to four labeled chemical
probes and proteins simultaneously and repeatedly in four dimensions (3D + time)
with subcellular resolution in real time. Transgenic fluorescently labeled
proteins, delivery of plasmids, and photo-activatable probes enhance these
possibilities. Thus, multi-photon microscopy has greatly extended our ability to
understand cell biology intra-vitally at cellular and subcellular levels. For
example, evaluation of rat surface glomeruli and accompanying proximal tubules
has shown the long held paradigm regarding limited albumin filtration under
physiologic conditions is to be questioned. Furthermore, the role of proximal
tubules in determining albuminuria under physiologic and disease conditions was
supported by direct visualization and quantitative analysis.
PMID- 25125751
TI - Role of inflammation and inflammatory mediators in colorectal cancer.
AB - Chronic inflammation is a risk factor for several different cancers including
colorectal cancer (CRC). However, the mechanisms underlying the contribution of
inflammation to cancer remain elusive. Pro-inflammatory mediators such as
cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2) contribute to cancer
progression. Here, we show that COX-2 is an immediate-early response gene induced
by growth factors and pro-inflammatory cytokines and its levels are elevated in
human CRCs. Furthermore, we show that COX-2-derived PGE2 promotes colonic tumor
growth via silencing certain tumor suppressors and DNA repair genes by DNA
methylation in colonic epithelial tumor cells. We also report that C-X-C motif
chemokine receptor 2 accelerates colonic inflammation and colitis-associated
tumorigenesis by mediating myeloid-derived suppressor cell recruitment to the
tumor microenvironment. These findings not only support a rationale to target
these pro-inflammatory pathways for cancer prevention and treatment but also
provide support for developing new therapeutic approaches to subvert chronic
inflammation- and tumor-induced immunosuppression.
PMID- 25125767
TI - Adaptive Multivariate Global Testing.
AB - We present a methodology for dealing with recent challenges in testing global
hypotheses using multivariate observations. The proposed tests target situations,
often arising in emerging applications of neuroimaging, where the sample size n
is relatively small compared with the observations' dimension K. We employ
adaptive designs allowing for sequential modifications of the test statistics
adapting to accumulated data. The adaptations are optimal in the sense of
maximizing the predictive power of the test at each interim analysis while still
controlling the Type I error. Optimality is obtained by a general result
applicable to typical adaptive design settings. Further, we prove that the
potentially high-dimensional design space of the tests can be reduced to a low
dimensional projection space enabling us to perform simpler power analysis
studies, including comparisons to alternative tests. We illustrate the
substantial improvement in efficiency that the proposed tests can make over
standard tests, especially in the case of n smaller or slightly larger than K.
The methods are also studied empirically using both simulated data and data from
an EEG study, where the use of prior knowledge substantially increases the power
of the test. Supplementary materials for this article are available online.
PMID- 25125768
TI - Differences by mother's education in the effect of childcare on child obesity.
AB - Previous studies have found adverse effects of maternal employment on child
obesity for higher educated mothers. Using a quasi-structural model, we find
additionally a lower risk of obesity for children of less educated mothers with
increased time in non-parental childcare.
PMID- 25125766
TI - Alcohol Environment, Perceived Safety, and Exposure to Alcohol, Tobacco, and
Other Drugs in Early Adolescence.
AB - This study examined the association between the count of alcohol outlets around
children's homes and opportunities to use alcohol, tobacco, and other drugs
(ATOD) during pre-adolescence. Data were collected in 2007 from 394 Baltimore
City children aged 8-13 (86% African American). Participants' residential address
and alcohol outlet data were geocoded with quarter mile (i.e., walking distance)
buffers placed around each participant's home to determine the number of outlets
within walking distance. The unadjusted logistic regression models revealed that
each unit increase in the number of alcohol outlets was associated with a 14%
increase in the likelihood of children seeing people selling drugs (OR=1.14,
p=.04) and a 15% increase in the likelihood of seeing people smoking marijuana
(OR=1.15, p<.01). After adjusting for neighborhood physical disorder, the
relationship between alcohol outlets and seeing people selling drugs and seeing
people smoking marijuana was fully attenuated. These results suggest that alcohol
outlets are one aspect of the larger environmental context that is related to
ATOD exposure in children. Future studies should examine the complex relationship
between neighborhood physical disorder and the presence of alcohol outlets.
PMID- 25125769
TI - Permanency Outcomes for Toddlers in Child Welfare Two Years After a Randomized
Trial of a Parenting Intervention.
AB - This study reports on child welfare outcomes of a community based, randomized
control trial of Promoting First Relationships(r) (PFR; Kelly, Sandoval,
Zuckerman, & Buehlman, 2008), a 10-week relationship-based home visiting program,
on stability of children's placements and permanency status two years after
enrollment into the study. Toddlers 10 - 24 months (N = 210) with a recent
placement disruption were randomized, along with their birth or foster/kin
parents, to PFR (n = 105) or a comparison condition (n = 105). A stable placement
had no interruptions or disruptions. A permanent placement was a stable placement
ending with a legal discharge to the study caregiver. Logistic regression models
predicting the dichotomous stability and permanency variables, controlling for
caregiver type, child welfare variables, and caregiver commitment, were
conducted. There was no difference by intervention group on stability or
permanency, but there was a significant interaction between caregiver type (birth
parent vs. foster/kin) and intervention group. More foster/kin caregivers who
received the PFR intervention provided stable, uninterrupted care and eventually
adopted or became the legal guardians of the toddlers in their care, compared to
foster/kin caregivers randomized to the comparison condition.
PMID- 25125770
TI - Psychology and the Rationality of Emotion.
AB - Questions addressed by recent psychological research on emotion include questions
about how thought shapes emotion and how emotion, in turn, shapes thought.
Research on emotion and cognition paints a somewhat different picture than that
seen in traditional discussions of passion and reason. This article reviews
several aspects of this research, concentrating specifically on three views of
rationality: Rationality as Process, Rationality as Product, and Rationality as
Outcome.
PMID- 25125771
TI - Perceptual and cognitive biases in individuals with body dysmorphic disorder
symptoms.
AB - Given the extreme focus on perceived physical defects in body dysmorphic disorder
(BDD), we expected that perceptual and cognitive biases related to physical
appearance would be associated with BDD symptomology. To examine these
hypotheses, participants (N = 70) high and low in BDD symptoms completed tasks
assessing visual perception and cognition. As expected, there were significant
group differences in self-, but not other-, relevant cognitive biases. Perceptual
bias results were mixed, with some evidence indicating that individuals high
(versus low) in BDD symptoms literally see themselves in a less positive light.
Further, individuals high in BDD symptoms failed to demonstrate a normative self
enhancement bias. Overall, this research points to the importance of assessing
both cognitive and perceptual biases associated with BDD symptoms, and suggests
that visual perception may be influenced by non-visual factors.
PMID- 25125772
TI - Emotion expression among abusive mothers is associated with their children's
emotion processing and problem behaviours.
AB - The current study evaluated the quality of facial and vocal emotional expressions
in abusive and non-abusive mothers, and assessed whether mothers' emotional
expression quality was related to their children's cognitive processing of
emotion and behavioural problems. Relative to non-abusive mothers, abusive
mothers produced less prototypical angry facial expressions, and less
prototypical angry, happy, and sad vocal expressions. The intensity of mothers'
facial and vocal expressions of anger was related to their children's
externalising and internalising symptoms. Additionally, children's cognitive
processing of their mothers' angry faces was related to the quality of mothers'
facial expressions. Results are discussed with respect to the impact of early
emotional learning environments on children's socioemotional development and risk
for psychopathology.
PMID- 25125773
TI - Equilibrium Conformations of Concentric-tube Continuum Robots.
AB - Robots consisting of several concentric, preshaped, elastic tubes can work
dexterously in narrow, constrained, and/or winding spaces, as are commonly found
in minimally invasive surgery. Previous models of these "active cannulas" assume
piecewise constant precurvature of component tubes and neglect torsion in curved
sections of the device. In this paper we develop a new coordinate-free energy
formulation that accounts for general preshaping of an arbitrary number of
component tubes, and which explicitly includes both bending and torsion
throughout the device. We show that previously reported models are special cases
of our formulation, and then explore in detail the implications of torsional
flexibility for the special case of two tubes. Experiments demonstrate that this
framework is more descriptive of physical prototype behavior than previous
models; it reduces model prediction error by 82% over the calibrated bending-only
model, and 17% over the calibrated transmissional torsion model in a set of
experiments.
PMID- 25125774
TI - The Knowledge Broker's "Fit" in the World of Knowledge Translation.
PMID- 25125775
TI - Lower-limb kinematics of single-leg squat performance in young adults.
AB - PURPOSE: To determine the kinematic parameters that characterize good and poor
single-leg squat (SLS) performance. METHODS: A total of 22 healthy young adults
free from musculoskeletal impairment were recruited for testing. For each SLS,
both two-dimensional video and three-dimensional motion analysis data were
collected. Pelvis, hip, and knee angles were calculated using a reliable and
validated lower-limb (LL) biomechanical model. Two-dimensional video clips of
SLSs were blindly assessed in random order by eight musculoskeletal
physiotherapists using a 10-point ordinal scale. To facilitate between-group
comparisons, SLS performances were stratified by tertiles corresponding to poor,
intermediate, and good SLS performance. RESULTS: Mean ratings of SLS performance
assessed by physiotherapists were 8.3 (SD 0.5), 6.8 (SD 0.7), and 4.0 (SD 0.8)
for good, intermediate, and poor squats, respectively. Three-dimensional analysis
revealed that people whose SLS performance was assessed as poor exhibited
increased hip adduction, reduced knee flexion, and increased medio-lateral
displacement of the knee joint centre compared to those whose SLS performance was
assessed as good (p<=0.05). CONCLUSIONS: Overall, poor SLS performance is
characterized by inadequate knee flexion and excessive frontal plane motion of
the knee and hip. Future investigations of SLS performance should consider
standardizing knee flexion angle to illuminate other influential kinematic
parameters.
PMID- 25125776
TI - Understanding physiotherapists' roles in ontario primary health care teams.
AB - PURPOSE: To understand physiotherapists' roles and how they are enacted within
Ontario primary health care (PHC) teams. METHODS: Following a pragmatic grounded
theory approach, 12 physiotherapists practising within Ontario PHC teams
participated in 18 semi-structured in-depth in-person interviews. All interviews
were audiotaped and transcribed verbatim, then entered into NVIVO-8. Coding
followed three progressive analytic stages and was iterative in nature, guided by
grounded theory. An explanatory scheme was developed. RESULTS: Physiotherapists
negotiate their place within the PHC teams through five interrelated roles: (1)
manager; (2) evaluator; (3) collaborator; (4) educator; and (5) advocate. These
five roles are influenced by three contextual layers: (1) inter-professional
team; (2) community and population served; and (3) organizational structure and
funding. Canada's PHC mandate (access, teams, information, and healthy living)
frame the contexts that influence role enactment. CONCLUSIONS: To fulfill the PHC
mandate, physiotherapists carry out multiple roles that are based on a broad
holistic perspective of health, within the context of a collaborative inter
professional team and the community, through an evidenced-informed approach to
care. There appear to be multiple ways of successfully integrating
physiotherapists within PHC teams, provided that role enactment is context
sensitive and congruent with the mandate of PHC.
PMID- 25125777
TI - Reliability and validity of two versions of the upper extremity functional index.
AB - PURPOSE: To examine the reliability, validity, and sensitivity to change of the
20-item version and the Rasch-refined 15-item version of the Upper Extremity
Functional Index (UEFI-20 and UEFI-15, respectively) and to determine the impact
of arm dominance on the positive minimal clinically important difference (pMCID).
METHODS: Adults with upper-extremity (UE) dysfunction completed the UEFI-20,
Upper Extremity Functional Scale (UEFS), Pain Limitation Scale, and Pain
Intensity Scale at their initial physiotherapy assessment (Time 1); 24-48 hours
later (Time 2); and 3 weeks into treatment or at discharge, whichever came first
(Time 3). Demographics, including working status, were obtained at Time 1. Global
ratings of change (GRC) were provided by the treating physiotherapist and patient
at Time 3. The UEFI-15 was calculated from relevant items in the UEFI-20. The
intra-class correlation coefficient (ICC) and minimal detectable change (MDC)
quantified test-retest reliability (Time 1-Time 2). Cross-sectional convergent
validity was determined by the association (Pearson's r) between Time 1 measures
of function and pain. Known-groups validity was evaluated with a one-way ANOVA
across three levels of working status. Longitudinal validity was determined by
the association (Pearson's r) between function and pain change scores (Time 1
Time 3). Receiver operating characteristic (ROC) curves estimated the pMCID using
Time 1-Time 3 change scores and average patient/therapist GRC. RESULTS:
Reliability for the UEFI-20 and UEFI-15 was the same (ICC=0.94 for both
measures). MDC values were 9.4/80 for the UEFI-20 and 8.8/100 for the UEFI-15.
Cross-sectional, known-groups, and longitudinal validity were confirmed for both
UEFI measures. pMCID values were 8/80 for the UEFI-20 and 6.7/100 for the UEFI
15; pMCID was higher for people whose non-dominant arm was affected. CONCLUSIONS:
Both UEFI measures show acceptable reliability and validity. Arm dominance
affects pMCID. The UEFI-15 is recommended because it measures only one dimension:
UE function.
PMID- 25125778
TI - Physiotherapists' perceptions of and experiences with the discharge planning
process in acute-care general internal medicine units in ontario.
AB - PURPOSE: To examine discharge planning of patients in general internal medicine
units in Ontario acute-care hospitals from the perspective of physiotherapists.
METHODS: A cross-sectional study using an online questionnaire was sent to
participants in November 2011. Respondents' demographic characteristics and
ranking of factors were analyzed using descriptive statistics; t-tests were
performed to determine between-group differences (based on demographic
characteristics). Responses to open-ended questions were coded to identify
themes. RESULTS: Mobility status was identified as the key factor in determining
discharge readiness; other factors included the availability of social support
and community resources. While inter-professional communication was identified as
important, processes were often informal. Discharge policies, timely availability
of other discharge options, and pressure for early discharge were identified as
affecting discharge planning. Respondents also noted a lack of training in
discharge planning; accounts of ethical dilemmas experienced by respondents
supported these themes. CONCLUSIONS: Physiotherapists consider many factors
beyond the patient's physical function during the discharge planning process. The
improvement of team communication and resource allocation should be considered to
deal with the realities of discharge planning.
PMID- 25125779
TI - Patients' perceptions of navigating "the system" for arthritis management: are
they able to follow our recommendations?
AB - PURPOSE: To understand whether a visit to a Hip/Knee Arthritis Assessment Centre
(AC), where non-surgical candidates with arthritis are directed toward community
resources and provided with a conservative treatment "prescription," contributes
to patients' self-management and ability to access community resources. METHODS:
A purposive sample of non-surgical patients was contacted 3-10 months after their
AC visit. Three focus groups (n=20) and 20 semi-structured telephone interviews
were conducted. Transcripts were systematically coded and analyzed using a
qualitative descriptive research methodology. RESULTS: While participants
generally reported that the AC visit improved self-management, analysis
identified an emergent theme about the inadequacy of conservative management in
general, subdivided into two sub-themes related to (1) limited access to high
quality, non-surgical treatment, such as physiotherapy and (2) health care
providers' attitudes and approaches, which do not embrace chronic disease
prevention and management. CONCLUSIONS: An AC visit contributes to arthritis self
management; however, the current health care system does not adequately support
conservative treatment of chronic conditions. Treatment guidelines need to be
tailored to the local health care context in which they are applied.
PMID- 25125780
TI - Clinician's Commentary on Winter Di Cola et al.(1.).
PMID- 25125783
TI - Clinician's Commentary on Duong et al.(1.).
PMID- 25125782
TI - Developing a physiotherapy-specific preliminary clinical decision-making tool for
oxygen titration: a modified delphi study.
AB - PURPOSE: To develop and evaluate a preliminary clinical decision-making tool
(CDMT) to assist physiotherapists in titrating oxygen for acutely ill adults in
Ontario. METHODS: A panel of 14 experienced cardiorespiratory physiotherapists
was recruited. Factors relating to oxygen titration were identified using a
modified Delphi technique. Four rounds of questionnaires were conducted, during
which the goals were to (1) generate factors, (2) reduce factors and debate
contentious factors, (3) finalize factors and develop the preliminary CDMT, and
(4) evaluate the usability of the tool in a clinical context. RESULTS: The panel
reached consensus on a total of 89 factors, which were compiled to create the
preliminary CDMT. The global tool reached consensus for sensibility, receiving a
mean score of 6/7 on a 7-point Likert-type scale (1=unacceptable; 7=excellent).
Five of the nine individual components of evaluation of the tool achieved scores
>=6.0; the remaining four had mean scores between 5.4 and 5.9. CONCLUSION: This
study produced a preliminary CDMT for oxygen titration, which the panel agreed
was highly comprehensible and globally sensible. Further research is necessary to
evaluate the sensibility and applicability of the tool in a clinical setting.
PMID- 25125781
TI - A survey of physiotherapists' experience using outcome measures in total hip and
knee arthroplasty.
AB - PURPOSE: To identify physiotherapists' familiarity with and experience using
outcome measures (OMs) along the care continuum for patients undergoing total
joint arthroplasty (TJA) of the hip and knee. Views on future use and barriers
were also captured. METHODS: A stratified random sample of physiotherapists in
one Canadian province completed a questionnaire about 19 standardized and
clinically feasible OMs. Analyses included descriptive statistics and chi-square
and McNemar tests to compare use of OMs for clinical decision making and program
evaluation. RESULTS: Of 694 physiotherapists surveyed, 298 (43%) responded. Of
these, 172 (58%) treated TJA clients and completed the full questionnaire. A
majority worked in public practice settings and >1 care phase (e.g., pre-op,
acute, rehab). All physiotherapists reported using >=1 OM and having greater
experience using performance-based measures than patient-reported OMs. OMs were
used more often for clinical decision making than for program evaluation.
Dissatisfaction with available tools was evident from respondents' comments.
Several barriers to using OMs were identified in varied clinical settings and
care phases. CONCLUSIONS: While physiotherapists use a variety of OMs along the
TJA continuum, there remain challenges to routine use across clinical settings,
care phases, and patient sub-groups.
PMID- 25125784
TI - Contact with Young Adults with Disability Led to a Positive Change in Attitudes
toward Disability among Physiotherapy Students.
AB - PURPOSE: To determine whether contact over 8 weeks with a person with disability
benefits physiotherapy students' attitudes toward disability and their
development of professional behaviours and skills. METHODS: Sixteen adults with
Down syndrome were matched with 16 physiotherapy students (13 women, 3 men; mean
age 22.5 [SD 3.0] years) and randomized to either an 8-week, twice-weekly walking
programme or an 8-week, once-weekly social activities programme. Students
completed the Interaction with Disabled Persons scale, the Community Living
Attitudes scale, and the Barriers to Exercise scale and rated their competency in
professional behaviours and skills. RESULTS: There were no differences between
the groups for any outcome. Across both groups, students showed positive changes
in attitudes toward disability, self-ratings of professional behaviours, and
confidence in working with people with disability. CONCLUSIONS: After an 8-week
programme, physiotherapy students reported being more comfortable with and having
more confidence in working with people with disability. These data support the
idea that contact with people with disability in community settings has positive
benefits for physiotherapy students, regardless of the content of the experience.
PMID- 25125785
TI - Clinicians' commentary on shields and taylor(1.).
PMID- 25125786
TI - An Improvised "Blow Glove" Device Produces Similar PEP Values to a Commercial PEP
Device: An Experimental Study.
AB - BACKGROUND: Postoperative positive expiratory pressure (PEP) therapy promotes
increased lung volume, secretion clearance, and improved oxygenation. Several
commercial devices exist that produce recommended PEP values (10-20 cmH2O) when
the patient breathes through a fixed orifice resistor. It was hypothesized that
an inexpensive, improvised "blow glove" device would produce similar PEP values
over a wider range of expiration volumes and flow rates. METHODS: PEP for
different expiration volumes (400-2000 mL) and expiratory flow rates (10-80
L/min) was compared between a commercial PEP device (Resistex, Mercury Medical,
Clearwater, FL) and an improvised "blow glove" device, recorded by a Vela
ventilator (CareFusion, San Diego, CA). Dynamics in positive end expiratory
pressure (PEEP) values were evaluated following five consecutive expirations. The
"blow glove" device was evaluated using various glove compositions and sizes.
RESULTS: The improvised "blow glove" device produced a significantly higher rate
of PEP values in the recommended range than the Resistex device (88.9% vs. 20%,
p<0.0001). No significant difference was observed between small and large glove
sizes (88.9% vs. 82.9%, p>0.05), but the powdered latex glove showed a
significantly higher rate of PEP values in the recommended range than the powder
free latex glove (88.9% vs. 44.4%, p<0.001). CONCLUSIONS: A "blow glove" PEP
device using a powdered latex glove produces PEP values in the recommended range
over a wider spectrum of expiratory flow rates and expiration volumes than a
commercial PEP device.
PMID- 25125789
TI - Clinician's Commentary on Anderson et al.(1.).
PMID- 25125788
TI - What clinical instructors want: perspectives on a new assessment tool for
students in the clinical environment.
AB - PURPOSE: Many Canadian physical therapy education programs use the 1997 version
of the Physical Therapist Clinical Performance Instrument (PT-CPI) to evaluate
students in their clinical placements. Recent evidence that clinical instructors
(CIs) are unsatisfied with the PT-CPI, however, suggests a need to develop a new
assessment tool. The purpose of this study was to gather Canadian CIs'
perspectives on rating scales, preferred training methods, and format for future
tool development. METHODS: This qualitative descriptive study involved five focus
groups from across Canada. English-speaking CIs who had supervised at least one
Canadian student in clinical practice were eligible for the study. RESULTS:
Participants identified concerns with the PT-CPI and indicated a preference for
(1) more objective rating scales with clearly defined anchors, (2) both in-person
and online training methods for CIs, and (3) a tool that could be completed and
reviewed on paper or online. CONCLUSIONS: CIs affirmed the need to develop a new
assessment tool. RESULTS of the study will be used to inform the development of a
new assessment tool to better evaluate Canadian physical therapy students'
performance in the clinical setting.
PMID- 25125787
TI - The Development and Testing of a Checklist to Study Behaviour Change Techniques
used in a Treatment Programme for Canadian Armed Forces Members with Chronic Non
specific Low Back Pain.
AB - PURPOSE: There are reports of increased use of a variety of behaviour change
techniques (BCT) by physiotherapists and findings of beneficial effects of use.
However, there is a lack of physiotherapy-specific definitions of these
techniques, as well as a sense of how physiotherapists use them in practice.
Through this study, the authors created and field tested a preliminary
nomenclature and description for BCT in patients with chronic non-specific low
back pain (CNSLBP). METHODS: Items for the Physiotherapy Behaviour Change
Technique (PT-BCT) checklist were derived from a nomenclature created for use in
psychology and also from publications of studies using cognitive behaviour
therapy-based approaches in physiotherapy. Content validity was tested via survey
of clinical and research experts. Videotapes of a 6-week patient self-management
rehabilitation programme were used for training, reliability testing, and field
testing of the PT-BCT checklist. RESULTS: Checklist items were endorsed by the
majority of experts surveyed; intra- and inter-rater reliability were moderate to
high. In the field study, a broad range of BCT types (behavioural, cognitive, and
motivational) were observed in both classroom and gym settings. CONCLUSIONS: The
BCT nomenclature arising from this study and the PT-BCT checklist will be useful
to further explore behaviour change in physiotherapy practice. The observation in
this study that BCT were integrated into physiotherapists' practice illustrates
how physiotherapists can play a role in changing behaviour, specifically in the
presence of CNSLBP.
PMID- 25125790
TI - What Does the Cochrane Collaboration Say about Exercises for Osteoarthritis?
PMID- 25125791
TI - Frustrated Freedom: The Effects of Agency and Wealth on Wellbeing in Rural
Mozambique.
AB - In Sen's capability view of poverty, wellbeing is threatened by both deficits of
wealth and deficits of individual agency. Sen further predicts that "unfreedom,"
or low levels of agency will suppress the wellbeing effects of higher levels of
wealth. The current paper extends Sen's view to include a condition, labeled
"frustrated freedom," in which relatively higher levels of agency can heighten
the poverty effects of relatively low levels of material wealth. Applying data
from a large scale population study of female heads of household in rural
Mozambique, the paper empirically tests Sen's view and the proposed extension. As
predicted, agency is found to moderate the relationship between agency, wealth,
and wellbeing, uncovering evidence of both unfreedom and frustrated freedom in
the population. Further research into the complex dynamics of wellbeing and
poverty are called for by the authors.
PMID- 25125792
TI - Adhesion Force Measurements Using an Atomic Force Microscope Upgraded with a
Linear Position Sensitive Detector.
AB - The atomic force microscope (AFM), in addition to providing images on an atomic
scale, can be used to measure the forces between surfaces and the AFM probe. The
potential uses of mapping the adhesive forces on the surface include a spatial
determination of surface energy and a direct identification of surface proteins
through specific protein-ligand binding interactions. The capabilities of the AFM
to measure adhesive forces can be extended by replacing the four-quadrant
photodiode detection sensor with an external linear position sensitive detector
and by utilizing a dedicated user-programmable signal generator and acquisiton
system. Such an upgrade enables the microscope to measure in the larger dynamic
range of adhesion forces, improves the sensitivity and linearity of the
measurement, and eliminates the problems inherent to the multiple repetitious
contacts between the AFM probe and the specimen surface.
PMID- 25125793
TI - Effects of Discrete Protein-Surface Interactions in Scanning Force Microscopy
Adhesion Force Measurements.
AB - The potential for measuring specific molecular recognition forces between probe
bound ligands and surface-bound proteins using a scanning force microscope (SFM)
has recently gained much attention. Generally, observed discontinuities in the
SFM force-displacement curves are attributed to the breaking of discrete,
specific affinity bonds. The present study on the molecular recognition system
composed of surface-immobilized antifluorescyl IgG molecules and SFM probe-bound
fluorescein ligands has demonstrated that similar intermittent discontinuities in
the SFM force-displacement curves may in fact be largely due to nonspecific
discrete interactions between the protein and the SFM probe. The mechanical
behavior of the cantilever-spherical bead system used in this study is discussed,
as it appears to cause a false indication of the separation distance between the
surface and probe. The strong lateral interactions which result in "stick and
slip"-like discontinuities seen in the adhesion curves are likely the result of
localized adhesion due to the heterogeneous nature of proteins and the lack of
molecular mobility allowed in the experimental system. The effect is magnified
with increasing contact time between the protein and probe. Factors which may
cause such anomalous behavior in a specific ligand-protein system are discussed
in order to avoid misinterpretation of SFM adhesion measurements.
PMID- 25125794
TI - In-Situ Atomic Force Microscope Imaging of Calcite Etch Pit Morphology Changes in
Undersaturated and 1-Hydroxyethylidene-1,1-diphosphonic Acid Poisoned Solutions.
AB - Morphology changes in etch pits formed on the (1014) cleavage plane of calcite
were induced by varying the ratio of [Ca2+] to [CO32-] in the bulk solution as
well as through the addition of the crystal poison 1-hydroxyethylidene-1,1
diphosphonic acid (HEDP). Three distinct morphologies were noted: symmetric
rhombic, asymmetric rhombic, and triangular with a rough curved hypotenuse. The
latter represents a transient morphology which is only observed during the actual
dissolution process, while the former morphologies persist after dissolution is
halted.
PMID- 25125795
TI - Human Growth Hormone Adsorption Kinetics and Conformation on Self-Assembled
Monolayers.
AB - The adsorption process of the recombinant human growth hormone on organic films,
created by self-assembly of octadecyltrichlorosilane, arachidic acid, and
dipalmitoylphosphatidylcholine, is investigated and compared to adsorption on
silica and methylated silica substrates. Information on the adsorption process of
human growth hormone (hGH) is obtained by using total internal reflection
fluorescence (TIRF). The intensity, spectra, and quenching of the intrinsic
fluorescence emitted by the growth hormone's single tryptophan are monitored and
related to adsorption kinetics and protein conformation. For the various
alkylated hydrophobic surfaces with differences in surface density and
conformational freedom it is observed that the adsorbed amount of growth hormone
is relatively large if the alkyl chains are in an ordered structure while the
amounts adsorbed are considerably lower for adsorption onto less ordered alkyl
chains of fatty acid and phospholipid layers. Adsorption on methylated surfaces
results in a relatively large conformational change in the growth hormone's
structure, as displayed by a 7 nm blue shift in emission wavelength and a large
increase in the effectiveness of fluorescence quenching. Conformational changes
are less evident for hGH adsorption onto the fatty acid and phospholipid alkyl
chains. Adsorption kinetics on the hydrophilic head groups of the self-assembled
monolayers are similar to those on solid hydrophilic surfaces. The relatively
small conformational changes in the hGH structure observed for adsorption on
silica are even further reduced for adsorption on fatty acid head groups.
PMID- 25125796
TI - Validation of a flow-structure-interaction computation model of phonation.
AB - Computational models of vocal fold (VF) vibration are becoming increasingly
sophisticated, their utility currently transiting from exploratory research to
predictive research. However, validation of such models has remained largely
qualitative, raising questions over their applicability to interpret clinical
situations. In this paper, a computational model with a segregated implementation
is detailed. The model is used to predict the fluid-structure interaction (FSI)
observed in a physical replica of the VFs when it is excited by airflow. Detailed
quantitative comparisons are provided between the computational model and the
corresponding experiment. First, the flow model is separately validated in the
absence of VF motion. Then, in the presence of flow-induced VF motion,
comparisons are made of the flow pressure on the VF walls and of the resulting VF
displacements. Self-similarity of spatial distributions of flow pressure and VF
displacements is highlighted. The self-similarity leads to normalized pressure
and displacement profiles. It is shown that by using linear superposition of
average and fluctuation components of normalized computed displacements, it is
possible to determine displacements in the physical VF replica over a range of VF
vibration conditions. Mechanical stresses in the VF interior are related to the
VF displacements, thereby the computational model can also determine VF stresses
over a range of phonation conditions.
PMID- 25125797
TI - Novel procedure for thermal equilibration in molecular dynamics simulation.
AB - We describe a simple novel procedure for achieving thermal equilibration between
a protein and a surrounding solvent during molecular dynamics (MD) simulation.
The method uniquely defines the length of simulation time required to achieve
thermal equilibrium over a broad range of parameters, thus removing ambiguities
associated with the traditional heuristic approaches. The proposed protocol saves
simulation time and avoids bias introduced by the inclusion of non-equilibrium
events. The key element of the procedure involves coupling only the solvent atoms
to a standard heat bath. Measuring progress towards thermal equilibration
involves simply monitoring the difference in temperature between the solvent and
the protein. Here, we report that the results of MD simulations using the above
procedure are measurably improved relative to the traditional approaches in terms
of root-mean-square deviations and principal components analysis both indicating
significantly less undesirable divergence.
PMID- 25125798
TI - Testing Scientific Software: A Systematic Literature Review.
AB - CONTEXT: Scientific software plays an important role in critical decision making,
for example making weather predictions based on climate models, and computation
of evidence for research publications. Recently, scientists have had to retract
publications due to errors caused by software faults. Systematic testing can
identify such faults in code. OBJECTIVE: This study aims to identify specific
challenges, proposed solutions, and unsolved problems faced when testing
scientific software. METHOD: We conducted a systematic literature survey to
identify and analyze relevant literature. We identified 62 studies that provided
relevant information about testing scientific software. RESULTS: We found that
challenges faced when testing scientific software fall into two main categories:
(1) testing challenges that occur due to characteristics of scientific software
such as oracle problems and (2) testing challenges that occur due to cultural
differences between scientists and the software engineering community such as
viewing the code and the model that it implements as inseparable entities. In
addition, we identified methods to potentially overcome these challenges and
their limitations. Finally we describe unsolved challenges and how software
engineering researchers and practitioners can help to overcome them. CONCLUSIONS:
Scientific software presents special challenges for testing. Specifically,
cultural differences between scientist developers and software engineers, along
with the characteristics of the scientific software make testing more difficult.
Existing techniques such as code clone detection can help to improve the testing
process. Software engineers should consider special challenges posed by
scientific software such as oracle problems when developing testing techniques.
PMID- 25125799
TI - Print-to-Pattern Dry Film Photoresist Lithography.
AB - Here we present facile microfabrication processes, referred to as Print-to
Pattern dry film photoresist (DFP) lithography, that utilize the combined
advantages of wax printing and DFP to produce micropatterned substrates with high
resolution over a large surface area in a non-cleanroom setting. The Print-to
Pattern methods can be performed in an out-of-cleanroom environment making
microfabrication much more accessible to minimally equipped laboratories. Two
different approaches employing either wax photomasks or wax etchmasks from a
solid ink desktop printer have been demonstrated that allow the DFP to be
processed in a negative tone or positive tone fashion, respectively, with
resolutions of 100 MUm. The effect of wax melting on resolution and as a bonding
material was also characterized. In addition, solid ink printers have the
capacity to pattern large areas with high resolution which was demonstrated by
stacking DFP layers in a 50 mm * 50 mm woven pattern with 1 mm features. By using
an office printer to generate the masking patterns, the mask designs can be
easily altered in a graphic user interface to enable rapid prototyping.
PMID- 25125802
TI - Rapid on-site cytological evaluation of transbronchial needle aspiration: Why
not?
PMID- 25125800
TI - Opposing roles of leptin and ghrelin in the equine corpus luteum regulation: an
in vitro study.
AB - Metabolic hormones have been associated with reproductive function modulation.
Thus, the aim of this study was: (i) to characterize the immunolocalization, mRNA
and protein levels of leptin (LEP), Ghrelin (GHR) and respective receptors LEPR
and Ghr-R1A, throughout luteal phase; and (ii) to evaluate the role of LEP and
GHR on progesterone (P4), prostaglandin (PG) E2 and PGF2alpha , nitric oxide
(nitrite), tumor necrosis factor-alpha (TNF); macrophage migration inhibitory
factor (MIF) secretion, and on angiogenic activity (BAEC proliferation), in
equine corpus luteum (CL) from early and mid-luteal stages. LEPR expression was
decreased in late CL, while GHR/Ghr-R1A system was increased in the same stage.
Regarding secretory activity, GHR decreased P4 in early CL, but increased
PGF2alpha , nitrite and TNF in mid CL. Conversely, LEP increased P4, PGE2,
angiogenic activity, MIF, TNF and nitrite during early CL, in a dose-dependent
manner. The in vitro effect of LEP on secretory activity was reverted by GHR,
when both factors acted together. The present results evidence the presence of
LEP and GHR systems in the equine CL. Moreover, we suggest that LEP and GHR play
opposing roles in equine CL regulation, with LEP supporting luteal establishment
and GHR promoting luteal regression. Finally, a dose-dependent luteotrophic
effect of LEP was demonstrated.
PMID- 25125801
TI - Cholecystokinin inhibits inducible nitric oxide synthase expression by
lipopolysaccharide-stimulated peritoneal macrophages.
AB - Cholecystokinin (CCK) was first described as a gastrointestinal hormone. However,
apart from its gastrointestinal effects, studies have described that CCK also
plays immunoregulatory roles. Taking in account the involvement of inducible
nitric oxide synthase- (iNOS-) derived NO in the sepsis context, the present
study was undertaken to investigate the role of CCK on iNOS expression in LPS
activated peritoneal macrophages. Our results revealed that CCK reduces NO
production and attenuates the iNOS mRNA expression and protein formation.
Furthermore, CCK inhibited the nuclear factor- (NF-) kappaB pathway reducing
IkappaBalpha degradation and minor p65-dependent translocation to the nucleus.
Moreover, CCK restored the intracellular cAMP content activating the protein
kinase A (PKA) pathway, which resulted in a negative modulatory role on iNOS
expression. In peritoneal macrophages, the CCK-1R expression, but not CCK-2R, was
predominant and upregulated by LPS. The pharmacological studies confirmed that
CCK-1R subtype is the major receptor responsible for the biological effects of
CCK. These data suggest an anti-inflammatory role for the peptide CCK in
modulating iNOS-derived NO synthesis, possibly controlling the macrophage
activation through NF-kappaB, cAMP-PKA, and CCK-1R pathways. Based on these
findings, CCK could be used as an adjuvant agent to modulate the inflammatory
response and prevent systemic complications commonly found during sepsis.
PMID- 25125803
TI - Mycobacterium and sarcoidosis: Old wine in a new bottle.
PMID- 25125804
TI - Diagnostic utility of conventional transbronchial needle aspiration without rapid
on-site evaluation in patients with lung cancer.
AB - BACKGROUND: Endobronchial involvement is frequently absent in many patients with
bronchogenic carcinoma. Malignant involvement may be confined to lymph
nodes/peribronchial locations only or may be present along with endobronchial
lesions. Transbronchial needle aspiration (TBNA) is a flexible bronchoscopic
technique which can be employed to obtain tissue samples from mediastinal lymph
nodes or peribronchial locations. Although a safe and cost effective
bronchoscopic modality, it is frequently underutilized owing to concerns
regarding its diagnostic utility and safety. Herein, we describe our experience
over 1 year on the diagnostic utility of TBNA without rapid on-site evaluation
(ROSE) in patients with suspected diagnosis of lung cancer. MATERIALS AND
METHODS: We retrospectively reviewed the cases in which conventional TBNA-without
ROSE was performed for suspected lung cancer, between January 2012 and December
2012. Each lymph node station from which aspiration was performed was sampled
thrice and smears were prepared on slides which were later examined by a
cytopathologist. RESULTS: Twenty-six cases were retrieved in which conventional
TBNA without ROSE for suspected lung cancer with mediastinal involvement was
performed during the study period. Adequate lymph node sampling could be achieved
in 57.7% cases. Conventional TBNA was diagnostic in 11 out of the 26 (42.3%)
patients. The diagnostic yield improved to 73.3% in patients in whom an adequate
lymph nodal sample could be obtained. TBNA was the sole diagnostic sample in six
(54.5%) patients. Alternative diagnoses (sarcoidosis and tuberculosis) were
obtained in two patients. CONCLUSION: Conventional TBNA without ROSE is a safe
and efficacious flexible bronchoscopic procedure which should be performed
routinely from bronchoscopically accessible locations in patients with a
suspected diagnosis of lung cancer.
PMID- 25125805
TI - Vitamin D status in adult critically ill patients in Eastern India: An
observational retrospective study.
AB - BACKGROUND: The prevalence of vitamin D deficiency in critically ill patients has
been reported to be as high as 80%. There is insufficient data regarding the
relationship between 25-hydroxyvitamin D [25(OH) D] levels and outcomes in
medical intensive care unit (MICU). The goal of this study was to evaluate the
prevalence of 25(OH) D deficiency in MICU and its relationship with outcomes.
SUBJECTS AND METHODS: This was a retrospective study in a MICU of a teaching
medical college hospital of Eastern India. All patients admitted to MICU, who had
levels of 25(OH) D available, were included in the study. The discriminative
powers of admission and lowest 25(OH) D values regarding day-30 mortality were
evaluated by producing receiver operating curves (ROC). Binary end points were
analyzed by means of a Fisher's exact test. Continuous variables were compared by
using unpaired t-tests, Welch's tests, or Wilcoxon ranksum tests. All odds ratios
and their corresponding 95% confidence intervals were calculated according to the
profile-likelihood method. The time from inclusion to death in the two groups was
compared with the use of the log-rank test, and the results are presented as
Kaplan-Meier curves. Hazard ratios for death from hypo 25(OH) D were calculated
by logistic regression model. All P values were 2-tailed and P < 0.05 was
considered statistically significant. RESULTS: Of the 300 patients admitted
during the study period, 25(OH) D levels were available in 152 patients (50.6%).
Of these 152 patients, 15 patients (9.8%) had 25(OH) D insufficiency (20-29.9
ng/dL), 79 (51.9%) had 25(OH) D deficiency (0-19.9 ng/dL), and the levels were
normal (>30 ng/dl) in 58 (38.2%) patients. Most of the patients with deficient
25(OH) D levels were females (P < 0.05). Higher mortality (P = 0.01), increased
length of MICU stay, and prolonged ventilation were observed in patients with
25(OH) D deficiency. CONCLUSIONS: Patients with 25(OH) D deficiency in MICU have
increased hospital mortality, longer mechanical ventilation, and longer MICU
stay.
PMID- 25125806
TI - Chronic obstructive pulmonary disease and low bone mass: A case-control study.
AB - BACKGROUND AND OBJECTIVE: Low bone mass (osteopenia and osteoporosis) is one of
the effects associated with chronic obstructive pulmonary disease (COPD). There
is very little data from Saudi Arabia on COPD and low bone mass. This
retrospective study was done to assess the prevalence of osteoporosis and
osteopenia in COPD patients attending King Fahd Hospital of the University
(KFHU), Alkhobar. PATIENTS AND METHODS: After obtaining the ethical approval from
the research committee, all patients seen between at the King Fahd Hospital of
the University between January 2010 and December 2012 were included. The
inclusion criteria included a follow up of a minimum 2 years, and the Medical
Records should have the details of forced expiratory volume in one second (FEV1),
blood bone profile and bone biomarkers and dual-energy X-ray absorptiometry
(DEXA) scan. Patients were labeled as osteopenia if the T score was -<1 to <-2.5
and osteoporosis of <-2.5 as per the WHO definition of osteopenia and
osteoporosis. RESULTS: Seventy-three patients were being followed in the clinics
and 49 patients satisfied the inclusion criteria. The average age was 60.6 +/-
10.47 years; males were 43 and females 6. Three (6.1%) were normal and the
remaining 46 (93.9%) were with low bone mass. Thirty-two (65.3%) were
osteoporotic and 14 (28.57%) were osteopenic. The average duration of COPD was
4.5 +/- 6.2 years. Majority (n = 36, 73.4%) of patients were in the Global
Initiative for COPD (GOLD) class II and III. FEV1 was significantly lower in the
patients with low bone mass 1.66 +/- 0.60 versus 3.61 +/- 0.58 (P < 0.001).
CONCLUSIONS: Our study shows that over 90% of Saudi Arabian patients with COPD
suffer from osteopenia and osteoporosis and unfortunately they remain under
diagnosed and undertreated.
PMID- 25125808
TI - Primary mediastinal large B-cell lymphoma: Clinical features, prognostic factors
and survival with RCHOP in Arab patients in the PET scan era.
AB - OBJECTIVE: PMBCL is a distinct type of nonhodgkins lymphoma with specific
clinicopathological features. To clarify clinical features, treatment
alternatives and outcomes, we evaluated 28 Arab patients treated with
chemotherapy or radiotherapy between 2006 and 2011. PATIENTS AND METHODS: PMBCL
lymphoma patients identified according to WHO classification and treated at KCCC
between 2006 and 2011 were included in this study. Demographic and clinical data
are presented as means or medians. Overall survival was estimated using the
Kaplan-Meier method. Survival rates were compared using the log-rank test. A P <
0.05 was considered significant. RESULTS: The median age of the patients was 31
years and the male to female ratio was 2:1. Majority of the patients (75%)
presented with stage I/II disease. Most had features of local extension like
pleural effusion (18%) and SVCO (39%). Only 11% of the patients had bone marrow
involvement at presentation. 96% of the patients required biopsy from the
mediastinal mass either by image guided core biopsy (75%) or by surgical biopsy.
Most patients were treated by RCHOP and involved field radiotherapy. Patients
with positive PET scan after RCHOP chemotherapy received salvage chemotherapy and
BEAM autologous marrow transplant. The five year OS for the entire group was 85%
while the PFS was 73%. Patients who had PET scan for response evaluation had
better OS [P = 0.013] and PFS [P = 0.039] when compared with those patients who
received only radiotherapy based on CT scan evaluation. CONCLUSION: PMBCL is a
specific lymphoma entity seen in the young with good survival. The role of PET
scan for response evaluation and the type of consolidation therapy needs to be
further clarified.
PMID- 25125807
TI - Prevalence and correlates of osteoporosis in chronic obstructive pulmonary
disease patients in India.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a syndrome of
progressive airflow limitation caused by the abnormal inflammatory reaction of
the airway and lung parenchyma. Osteoporosis is one of the major extrapulmonary
manifestations of COPD. The, prevalence of osteoporosis in COPD patients in
Indian population is unknown. OBJECTIVES: To study the prevalence of osteoporosis
in COPD and to define various risk factors associated with reduced bone mineral
density (BMD) in COPD. MATERIALS AND METHODS: The study was done in the
department of Pulmonary Medicine of a tertiary care hospital. All the diagnosed
cases of COPD according to the Global Initiative for Obstructive Lung Disease
(GOLD) guidelines were included in this study. The present study was a
prospective study in for a period of 1 year. A brief history of the patients was
taken, especially regarding duration of illness, number of exacerbations in the
past 3 years, smoking in pack years, and history of steroid use (both systemic
and inhaled steroids) after which cumulative dose of steroids was calculated.
Spirometry was done in all these patients to stage the severity of COPD according
to GOLD criteria. DEXA scan of the lumbar spine was done using bone densitometer
to determine osteoporosis. A world Health Organization (WHO) criterion for
definition of osteoporosis was applied and patients with T-score of > -2.5
standard deviation (SD) were diagnosed to have osteoporosis, -1 SD to -2.5 SD
were diagnosed to have osteopenia and < -1 SD as normal. Statistical analysis for
association of COPD with osteoporosis was done using chi-square test. Risk
factors for osteoporosis were identified by univariate and multivariate logistic
regression analysis. RESULTS: A total of 102 COPD patients were included in the
study. Among these, 68 patients (66.6%) had osteoporosis and 20 patients (19.6%)
had osteopenia. Majority (64.7%) of the patients who had osteoporosis had stage
III and stage IV COPD disease. It was observed that as the severity grade of COPD
increased, the risk of osteoporosis also increased. The bone mineral density
(BMD) showed a significant difference among different stages of COPD. As the
severity of the stage of COPD increased, BMD decreased. It was also observed that
patients with lower body mass index (BMI) had higher prevalence of osteoporosis
(37.3%) as compared to overweight patients. On univariate analysis, it was
observed that risk factors for osteoporosis were female sex, higher number of
exacerbations, BMI, and severity of COPD. After using multivariate logistic
regression analysis, stage IV COPD (odds ratio (OR): 34.48, 95% confidence
interval (CI): 1.59-1,000, P < 0.02), number of acute exacerbations >3 (OR: 30.3,
95% CI: 4.74-200, P < 0.01), and steroid cumulative dose >1,000 mg (OR: 7.35, 95%
CI: 0.92-58.5, P < 0.04) were observed to be significant risk factors for
osteoporosis in COPD patients. CONCLUSIONS: In the present study, the prevalence
of osteoporosis was 66.6% and another 19.6% had osteopenia. As the severity of
COPD increased, the risk of osteoporosis increased. GOLD stage III and stage IV
patient had significantly lower BMD as compared to stage I and stage II of COPD
disease. Stage IV COPD disease, use of oral or parenteral glucocorticoids, and
repeated number of exacerbations were found to be independent risk factors for
osteoporosis in COPD patients. Thus, high clinical suspicion and early diagnosis
and treatment is required in the evaluation of osteoporosis in COPD patients so
that the quality of life can be improved in these patients.
PMID- 25125809
TI - A questionnaire-based study on the role of environmental factors in allergic
bronchopulmonary aspergillosis.
AB - BACKGROUND AND AIMS: Allergic bronchopulmonary aspergillosis (ABPA) is an
immunological disorder caused by hypersensitivity against Aspergillus fumigatus.
The pathogenesis of ABPA remains unknown. Few studies have investigated the role
of environmental factors in pathogenesis of ABPA. Herein, we investigate the role
of environmental factors in ABPA. MATERIALS AND METHODS: In this prospective case
control study, consecutive patients with asthma (Aspergillus sensitized and
unsensitized) and ABPA were investigated using a standardized questionnaire to
enquire into their demographic characteristics, clinical details, exposure to
organic matter and living conditions (home environment, presence of moisture in
the walls, and others). Asthma severity and control was assessed using the 2002
The Global Initiative for Asthma (GINA) recommendations and asthma control test,
respectively. RESULTS: During the study period, 202 subjects of asthma (103 and
99 Aspergillus unsensitized and sensitized asthma, respectively) and 101 ABPA
with a mean (SD) age of 35.3 (14.7) years were included. The baseline
characteristics were similar in the two groups except for a higher prevalence of
severe persistent asthma in the ABPA group (79% vs. 44%, P = 0.0001). No
significant differences in environmental factors were noted in the ABPA
population compared to asthmatic patients except for a higher rural residence in
ABPA (47% vs. 66%, P = 0.007). CONCLUSIONS: The study found no significant
environmental differences in ABPA compared to asthmatic patients. It is likely
that environmental factors are not the primary pathogenetic factors in causation
of ABPA.
PMID- 25125811
TI - Effect of type II diabetes mellitus on treatment outcomes of tuberculosis.
AB - CONTEXT: There is conflicting evidence of effect of diabetes on treatment of
tuberculosis (TB). There is a need to investigate effect of diabetes on outcomes
of TB treatment under field conditions in India. AIMS: To compare treatment
outcomes among TB patients with diabetes with those without diabetes. SETTING AND
DESIGN: Study was conducted in Cuddalore, Tamil Nadu, among patients registered
with Revised National TB Control Programme. Prospective observational study
design was used. MATERIALS AND METHODS: Registered TB patients aged 30 and above
were invited to participate in the study. Those who were not aware of their
diabetic status were diagnosed using oral glucose tolerance test. A total of 89
diabetic and 120 non-diabetic patients were recruited in the study. They were
followed up till the end of treatment and outcomes were recorded. STATISTICAL
ANALYSIS USED: Treatment outcomes in the two groups were compared using bi
variate and multi-variate analysis. RESULTS: Bi-variate (unadjusted) analysis
showed similar treatment success rates in the two groups. But, the adjusted odds
ratios for successful treatment among diabetic patients were significantly lower
(0.191, 95% CI 0.04-0.90) for pulmonary TB patients and for smear positive
pulmonary TB patients (odds ration 0.099, 0.013-0.761). Diabetes was found to be
predictor for sputum positivity at end of treatment. CONCLUSIONS: Diabetes
increases risk of poor treatment outcomes among pulmonary TB patients. The study
highlights need of screening of TB patients for diabetes. There is need to see
the effect of glycemic control on treatment outcomes among diabetics.
PMID- 25125810
TI - Prevalence of water pipe smoking in the city of Mashhad (North East of Iran) and
its effect on respiratory symptoms and pulmonary function tests.
AB - BACKGROUND: The prevalence of water pipe (WP) smoking was studied using a
standard questionnaire. Pulmonary function tests were also compared between WP
smokers and non-smokers. MATERIALS AND METHODS: The prevalence of WP smoking was
studied using a standard questionnaire. Pulmonary function tests including forced
vital capacity (FVC), forced expiratory volume in one second (FEV1), maximal mid
expiratory flow (MMEF), peak expiratory flow (PEF), maximal expiratory flow at
75%, 50%, and 25% of the FVC (MEF75,50,25) were compared between WP smokers and
non-smokers. RESULTS: A total of 673 individuals including 372 males and 301
females were interviewed. The number of WP smokers was 58 (8.6%) including 24
males (6.5%) and 34 females (11.3%). All pulmonary functional test (PFT) values
in WP smokers were lower as compared to the non-smokers (P < 0.05 to P < 0.001).
The prevalence and severity of respiratory symptoms (RS) in WP smokers were
higher than non-smokers (P < 0.05 to P < 0.001). There were negative correlations
between PFT values and positive correlation between RS and duration, rate, as
well as total smoking (duration X rate) (P < 0.05 to P < 0.001). CONCLUSION: In
this study the prevalence of WP smoking in Mashhad city was evaluated for the
first time. The results also showed a significant effect of WP smoking on PFT
values and respiratory symptoms.
PMID- 25125812
TI - Usage patterns of biomarkers in non-small-cell lung cancer patients in India:
Findings from a systematic review and survey.
AB - INTRODUCTION: Personalized medicine has facilitated improved management of non
small cell lung cancer (NSCLC) patients by identifying predictive and prognostic
biomarkers for enhanced efficiency of detection and efficacy of treatment. This
systematic review and survey assessed the patterns of biomarker usage, molecular
testing techniques to diagnose patients with NSCLC in India and testing
techniques recommended by cancer societies. MATERIALS AND METHODS: Studies were
retrieved from Embase, PubMed, and Cochrane databases for the last 12 years,
using relevant search strategies as per the Cochrane methodology for systematic
reviews. Outcomes of interest were biomarkers for NSCLC, patterns of biomarker
testing, diagnostic methods, guidelines and cost of biomarker testing. RESULTS:
In all, 499 studies were identified for screening and 17 primary publications
were included in the review. Epidermal growth factor receptor (EGFR) expression
and epithelial markers (particularly cytokeratins (CK)) were the most commonly
reported biomarkers (7/17) and immunohistochemical (IHC) staining was the most
common technique for detection of biomarkers. The frequency of EGFR mutations was
higher among women than men. Significantly elevated levels of CK-18 were observed
in patients with squamous cell carcinoma and of CK-19 in patients with
adenocarcinoma, squamous cell carcinoma, and NSCLC (P < 0.001). Prognostic or
predictive role of cytokines and angiogenic markers as well as DNA expression
were evaluated. The survey also showed that IHC was the most common technique for
detection of biomarkers. CONCLUSIONS: This systematic review and survey provides
valuable information on biomarker usage in the Indian population, and highlights
the need for initiatives required for future biomarker testing in India.
PMID- 25125813
TI - Incidental detection of a tumour on 68-Gallium DOTANOC PET/CT.
PMID- 25125814
TI - Hydatid cyst of lung: An uncommon cause of chest pain in young.
AB - Echinococcosis can involve any organ. The liver is the most common organ
involved, followed by the lungs. Depending on the location of involvement it can
have varied presentation. We describe a young adult presenting with chest pain
secondary to a pulmonary giant hydatid cyst. A pulmonary hydatid cyst should be
considered in the differential diagnosis of patients presenting with chest pain
without conventional risk factors of coronary artery disease, especially in a
tropical region.
PMID- 25125815
TI - Anaplastic thyroid carcinoma presenting as bilateral pleural effusion.
AB - Anaplastic thyroid cancer presenting as bilateral malignant pleural effusion is
rarely reported. We present a case who presented solely with respiratory symptoms
and subsequently found to be having bilateral malignant pleural effusion
secondary to anaplastic thyroid cancer.
PMID- 25125816
TI - Single-stage management of large pulmonary and hepatic hydatid cysts in pediatric
age group: Report of two cases.
AB - Two patients presented to us with very similar clinical and radiological
presentation of huge hydatid cysts in the lung and liver. The first patient was
an 11-year-old female child and the second one was a 9-year-old male child. The
clinical features in both were breathlessness on exertion, pain abdomen, and
abdominal distension. Chest Roentgenogram along with computed tomogram of the
chest and abdomen revealed presence of thin-walled homogenous large cysts, one in
the right lung and two in the liver, in both the cases. Although the liver cysts
were of larger size and occupying most of the right lobe of the liver and part of
the left lobe, liver function tests were normal. All three cysts were enucleated
in the same sitting by a combined thoracic and abdominal approach (thoracotomy
followed by laparotomy). After enucleation of the cyst, capitonnage of the cavity
in the lung was done and the liver cavities were filled with omentum to prevent
collection of fluid and abscess formation. Both patients recovered well, although
the second patient required abdominal drain for a long period of 1 month for bile
leakage which decreased gradually and eventually stopped.
PMID- 25125817
TI - Secondary pleural hydatidosis: Complication of intrapulmonary echinococcosis.
AB - Hydatid disease has a wide geographic distribution around the world. In human,
the liver is the most commonly affected organ, followed by the lungs.
Intrathoracic extrapulmonary locations are generally the mediastinum, pleura,
pericardium and chest wall. Pleural involvement usually follows the rupture of a
pulmonary or hepatic cyst inside the pleural space causing secondary pleural
hydatidosis. We report four cases of patients who were referred to our hospital
for management of pleural hydatid disease as a complication of intrapulmonary
echinococcosis.
PMID- 25125818
TI - Bronchial mucous gland adenoma presenting as massive hemoptysis: A diagnostic
dilemma.
AB - Mucous gland adenoma of the lung is an uncommon benign tumor that histologically
resembles the mucus-secreting component of tracheobronchial gland. The majority
arises within the main, lobar, or segmental bronchi but parenchymal involvement
had also been reported. We herein present a case of mucous gland adenoma arising
from the left lower lobe bronchus. The 32-year-old female presented with massive
hemoptysis, productive cough, and dyspnoea and was clinically misdiagnosed as
tuberculosis. Radiology proved to be inconclusive. This case highlights the
importance of a complete lung work up in patients presenting with signs of
respiratory tract infections.
PMID- 25125819
TI - Primary synovial sarcoma of lung.
AB - A synovial sarcoma (SS) is a rare form of cancer which usually occurs near the
joints of the arm, neck, or leg, but has been documented in most human tissues
and organs, including the brain, prostate, and heart. Primary pulmonary SS is an
extremely rare tumor. We report a case of primary SS of lung who presented with
severe chest pain and a large right lung mass with right-sided pleural effusion
in computed tomography (CT) scan of thorax. The diagnosis was made on the basis
of CT-guided core biopsy and immunohistochemistry. On immunohistochemistry, tumor
cell expressed epithelial membrane antigen, bcl 2, Vimentin and smooth muscle
actin and were immunonegative for S100 and cytokeratin. So, the final diagnosis
was primary SS.
PMID- 25125820
TI - Is femoral uptake of Tc99m-methylene diphosphonate on bone scintigraphy in
bronchogenic carcinoma an alarming sign: A case report and brief review of
literature?
AB - Detection of skeletal metastasis in patients with lung cancer is important from
management point of view. We report the bone scan finding in a patient with non
small cell lung carcinoma showing isolated abnormal tracer in femur and having a
characteristic appearance in computed tomography, highlighting the importance of
bone scan in patients with bronchogenic carcinoma.
PMID- 25125821
TI - Pulmonary alveolar proteinosis due to mycophenolate and cyclosporine combination
therapy in a renal transplant recipient.
AB - Pulmonary alveolar proteinosis (PAP) is an orphan disease characterized by the
accumulation of excess of surfactant within alveoli and bronchioles. The primary
form of PAP (P-PAP; also referred to as idiopathic or autoimmune) is the most
common form. It is mediated through a circulating neutralizing antibody against
granulocyte-macrophage colony-stimulating factor. Secondary PAP (S-PAP) can be
induced by a host of inciting agents and is far more liable to progress to
terminal respiratory failure. We describe a rare case of S-PAP occurring in a
renal transplant recipient due to mycophenolate and cyclosporine combination
therapy, which resolved spontaneously following withdrawal of these drugs.
PMID- 25125822
TI - Miliary nodules: An unusual presentation of allergic bronchopulmonary
aspergillosis.
AB - Allergic bronchopulmonary aspergillosis (ABPA) is an immune-mediated inflammatory
disease caused by hypersensitivity to Aspergillus fumigatus. A wide spectrum of
plain radiographic appearances has been described in ABPA, though none are
pathognomonic of ABPA. The common radiological abnormalities encountered are
fleeting pulmonary opacities, bronchiectasis, and mucoid impaction. Uncommon
radiological findings encountered in ABPA include pulmonary masses, perihilar
opacities simulating hilar adenopathy, and pleural effusions. However, miliary
nodules as a radiological presentation of ABPA are very rare and only one case
has been reported in literature. It is often misdiagnosed and mismanaged as
tuberculosis; thus, the clinician should be vigilant enough to diagnose this very
rare entity.
PMID- 25125823
TI - Community acquired Roseomonas infection in a pre-existing Tubercular lung lesion.
AB - Roseomonas are nonfermenting opportunistic Gram-negative bacilli belonging to the
newly established genus of Roseomonas. The clinical experience with the species
is limited and is difficult to diagnose because of limited expertise and lack of
commercially available identification kits with any of the automated systems.
This is a first ever reported case of secondary bacterial infection due to
Roseomonas genomospecies 6 in a patient of pulmonary tuberculosis from the Indian
subcontinent.
PMID- 25125824
TI - A 55 years old man with pulmonary alveolar microlithiasis.
AB - Pulmonary alveolar microlithiasis (PAM) is a very rare diffuse chronic lung
disease characterized by deposition of small spherules of calcium phosphate
within the alveolar cavity. The disease is usually seen from birth up to 40 years
of age and is usually diagnosed incidentally during radiography of the chest for
other reasons. Most of patients are asymptomatic or having very mild symptoms and
the majority of patients either have normal or restrictive pulmonary function
test. Clinically, the course of the disease is different; it remains static in
few patients or it may progress to pulmonary fibrosis, respiratory failure and
cor pulmonale in others. In this case report, we present a 55-year-old man who
presented with moderate shortness of breath which has progressed from mild
symptoms with in the previous years. His chest high-resolution CT scan showed
diffusely scattered, ill-defined little shadowy micronodules which involve the
left lung; lingula and left lower lobe in particular. A lung biopsy confirmed the
diagnosis of PAM. He was followed up for 1 year with treatment by steroid and
alendronate, and no progression was noticed in fact improvement in pulmonary
function test noticed. This is the first case report of PAM in Kurdistan.
PMID- 25125826
TI - Vitamin D status in critical care: Contributor or marker of poor health?
PMID- 25125825
TI - An unusual cause of recurrent pneumonia in adults.
AB - Selective IgM deficiency is a rare primary immunodeficiency defined as isolated
low levels of IgM. It presents with recurrent infections and has been described
as first presenting in adulthood with recurrent respiratory tract infections.
Unlike its better known counterpart of IgA deficiency, this particular
immunodeficiency is often overlooked. We present a case of selective IgM
deficiency who presented with recurrent respiratory infections.
PMID- 25125827
TI - Usher's syndrome: Can primarily be a primary ciliary disorder?
PMID- 25125828
TI - Congenital lobar emphysema presenting at late childhood: A rare case report.
PMID- 25125829
TI - Remarkable computed tomography findings in Boerhaave's syndrome.
PMID- 25125830
TI - Long-term doxycycline and lung function in chronic obstructive pulmonary disease:
A pilot observation.
PMID- 25125831
TI - Spontaneous resolution of pulmonary inflammatory pseudotumor.
PMID- 25125832
TI - Mucormycosis masquerading as an endobronchial tumor.
PMID- 25125833
TI - Extensive unilateral tuberculosis lung with segmental atresia of principal
bronchus.
PMID- 25125834
TI - Subclinical airflow obstruction in allergic rhinitis.
PMID- 25125835
TI - A letter in response to recurrent subcutaneous emphysema in a treated
tuberculosis patient: Is there any association?
PMID- 25125836
TI - Planning in case control studies: A comment on the relationship between lung
function and indoor air pollution among rural women in the Niger Delta region of
Nigeria.
PMID- 25125837
TI - Comments on pathogenesis of acquired tracheobronchoesophageal fistula following
blunt chest trauma.
PMID- 25125838
TI - Authors' reply.
PMID- 25125839
TI - CRIS Guidelines (Checklist for Reporting In-vitro Studies): A concept note on the
need for standardized guidelines for improving quality and transparency in
reporting in-vitro studies in experimental dental research.
AB - In vitro studies form a pivotal role in dental research contribution to a
substantial evidence base. The reporting standards of these studies are not
uniform thus resulting in lacunae in evidence reported. The effort of this
concept note is to propose a Checklist for Reporting in vitro Studies (CRIS
guidelines) that would promote quality and transparency in reporting in vitro
studies.
PMID- 25125841
TI - C-shaped root canal configuration: A review of literature.
AB - The aim is to review and discuss the etiology, incidence, anatomic features,
classification, diagnosis and management of the C-shaped canal configuration. C
shaped canal configuration is a variation that has a racial predilection and is
commonly seen in mandibular second molars. The intricacies present in this
variation of canal morphology can pose a challenge to the clinician during
negotiation, debridement and obturation. Manual and electronic searches of
literature were performed from 1979 to 2012, in Pub Med by crossing the keywords:
C-shaped canals, mandibular second molar, mandibular first premolar, root canal
morphology. Knowledge of the C-shaped canal configuration is essential to achieve
success in endodontic therapy. Radiographic and clinical diagnoses can aid in
identification and negotiation of the fan-shaped areas and intricacies of the C
shaped anatomy. Effective management of this anomalous canal configuration can be
achieved with rotary and hand instrumentation assisted with sonics and
ultrasonics. Modifications in the obturation techniques will ensure a 3
dimensional fill of the canal system and chamber retained restorations like
amalgam or composites, serve as satisfactory post endodontic restorations.
PMID- 25125840
TI - Validity of bond strength tests: A critical review: Part I.
AB - Adhesive systems are selected based on their bond strengths achieved while
testing in laboratories. These bond strengths can predict the longevity of a
restoration to some extent. There were several discrepancies in the reported bond
strengths. To critically review the reliability of macro-bond strength tests used
to evaluate resin-tooth interface. Relevant literature published between January
1983 and May 2013 was collected from PubMed database, Google scholar, and hand
searched journals of Conservative Dentistry, Endodontics and Dental materials.
Variables that influence the test outcome are categorized into substrate-related
factors, factors related to specimen properties, preparation of specimens, and
test methodology. Impact of these variables on the test outcome is critically
analyzed. There is lack of a standard format for reporting the bond strength
tests, which could lead to misinterpretation of the data and bonding abilities of
adhesives.
PMID- 25125843
TI - Effects of sports beverages and polishing systems on color stability of different
resin composites.
AB - BACKGROUND: Consumption of certain acidic beverages may alter the physical and
esthetic properties of resin composites. AIM: The aim of this study was to
evaluate the effects of two sports beverages on color stability of two different
types of resin composites polished with different composite polishing systems.
MATERIALS AND METHODS: A total of 96 disk-shaped specimens (diameter: 8-mm and
thickness: 2-mm) were made from two different resin composites (Cavex Quadrant
Universal-LC, and Clearfil-APX). All of the specimens were stored in distilled
water for 24 h at 37 degrees C. Color measurements of each specimen were
performed using a colorimeter according to the CIEL*a*b* color scale at baseline
and after seven days of immersion in two different sports beverages (Powerade and
Buzzer). STATISTICAL ANALYSIS USED: The data were evaluated using Kruskal Wallis
and Mann-Whitney U tests. RESULTS: Significant differences were found between the
mean DeltaE values of the groups after seven days of immersion (P < 0.05). The
highest level of the mean color change was observed in the Clearfil APX specimens
immersed in Powerade (DeltaE = 3.5 +/- 0.9). Control groups stored in distilled
water for both composites exhibited small color changes (DeltaE-Cavex-bur = 2.1
+/- 1; DeltaE-Clearfil APX-bur = 2.1 +/- 0.4). CONCLUSION: Sport beverages caused
discoloration in the resin composites after seven days.
PMID- 25125842
TI - Comparison of shear bond strength of composite resin to enamel surface with laser
etching versus acid etching: An in vitro evaluation.
AB - INTRODUCTION: The aim of the study is in vitro evaluation of the shear bond
strength of composite resin bonded to enamel which is pretreated using acid
etchant and Er,Cr:Ysgg. MATERIALS AND METHODS: 40 extracted human teeth were
divided in two groups of 20 each (Groups A and B). In Group A, prepared surface
of enamel was etched using 37% phosphoric acid (Scotchbond, 3M). In Group B,
enamel was surface treated by a an Er, Cr: YSGG laser system (Waterlase MD,
Biolase Technology Inc., San Clemente, CA, USA) operating at a wavelength of
2,780 nm and having a pulse duration of 140-200 microsecond with a repetition
rate of 20 Hz and 40 Hz. Bonding agent ((Scotchbond Multipurpose, 3M) was applied
over the test areas on 20 samples of Groups A and B each, and light cured.
Composite resin (Ceram X duo Nanoceramic restorative, Densply) was applied onto
the test areas as a 3 * 3 mm diameter bid, and light cured. The samples were
tested for shear bond strength. RESULTS: Mean shear bond strength for acid-etched
enamel (26.41 +/- 0.66MPa, range 25.155 to 27.150 MPa) was significantly higher
(P < 0.01) than for laser-etched enamel (16.23 +/- 0.71MPa, range 15.233 to
17.334 MPa). CONCLUSIONS: For enamel surface, mean shear bond strength of bonded
composite obtained after laser etching were significantly lower than those
obtained after acid etching.
PMID- 25125844
TI - Evaluation of smear layer removal from ultrasonically prepared retrocavities by
three agents.
AB - OBJECTIVES: To evaluate the efficacy of 35% orthophosphoric acid, 24%
ethylenediaminetetraacetic acid (EDTA) and 10% citric acid in the removal of
smear layer from retrocavities prepared with ultrasonic retro-tips using scanning
electron microscopy. MATERIALS AND METHODS: Root canals of fifty single-rooted
teeth were cleaned, shaped, and obturated with gutta-percha and AH plus sealer.
The apical 3 mm of each root was sectioned with a diamond disc and retrograde
cavities were prepared with Kis # 1 ultrasonic retro-tips to a depth of 3 mm.
Retro cavities in Group I were treated with a gel of 35% orthophosphoric acid for
15 seconds, Group II were treated with a gel of 24% EDTA at neutral pH for 2
minutes, and Group III were treated with a gel of 10% citric acid for 2 minutes,
followed by 1 minute rinsing with distilled water for all groups. The samples
were prepared for scanning electron microscopic observation. Scoring was
performed for the presence of the smear layer on the walls of the retrocavity.
RESULTS: In the orthophosphoric acid group, it was observed that all dentinal
tubules were open in 70% of the samples. The majority of analyzed samples in EDTA
and citric acid group showed dentinal tubules covered with the smear layer.
CONCLUSIONS: Application of 35% orthophosphoric acid gel for 15 seconds on
retrocavities prepared with ultrasonic retro-tips is the most effective means for
removal of smear layer.
PMID- 25125845
TI - Comparative evaluation of antimicrobial efficacy of triple antibiotic paste and
calcium hydroxide using chitosan as carrier against Candida albicans and
Enterococcus faecalis: An in vitro study.
AB - AIM: To analyze the sustained release of intracanal medicaments with or without a
carrier and testing their antimicrobial efficacy in root canal against Candida
albicans and Enterococcus faecalis. MATERIALS AND METHODS: A total of 80 single
rooted anterior teeth were selected, root canal preparation was done, and teeth
were divided into two halves and contaminated with C. albicans and E. faecalis,
which were further divided into four test groups each according to intracanal
medicaments used. Chitosan was used as vehicle for triple antibiotic paste (TAP)
and calcium hydroxide and antimicrobial assessment was performed on second and
seventh day. Dentine samples were collected after each. RESULTS: All four
medicaments used in this study showed antifungal and antibacterial activity.
Group II (TAP + chitosan) and Group III (Ca(OH)2 + chitosan) had the higher
antifungal and antibacterial activity compared with two other groups. CONCLUSION:
Combination of TAP + chitosan and Ca(OH)2 + chitosan produced better results
compared with the combination of medicaments with saline.
PMID- 25125846
TI - "Evaluation of sealing ability of MM-MTA, Endosequence, and biodentine as
furcation repair materials: UV spectrophotometric analysis".
AB - AIM: To evaluate the sealing ability of MICRO-MEGA Mineral Trioxide Aggregate,
Endosequence, Biodentine as furcation repair materials using a dye extraction
leakage method. MATERIALS AND METHODS: Forty mandibular molars were randomly
divided according to the material used for perforation repair. Group I- (left
unsealed) control, Group II-MICRO-MEGA Mineral Trioxide Aggregate, Group III -
Endosequence, Group IV - Biodentine. All samples were subjected to orthograde and
retrograde methylene blue dye challenge followed by dye extraction with 65%
nitric acid. Samples were then analyzed using Ultra violet (UV) Visible
Spectrophotometer. RESULTS: Biodentine showed highest dye absorbance, whereas
Endosequence showed lowest dye absorbance when compared with other repair
materials. CONCLUSION: Within the limitations of this study, it was observed that
Endosequence showed better sealing ability when compared with other root repair
materials.
PMID- 25125847
TI - Comparative evaluation of microleakage in Class II restorations using open vs.
closed centripetal build-up techniques with different lining materials.
AB - BACKGROUND: Evaluation of microleakage is important for assessing the success of
new restorative materials and methods. AIM AND OBJECTIVES: Comparative evaluation
of microleakage in Class II restorations using open vs. closed centripetal build
up techniques with different lining materials. MATERIALS AND METHODS:
Standardized mesi-occlusal (MO) and distoocclusal (DO) Class II tooth
preparations were preparedon 53 molars and samples were randomly divided into six
experimental groups and one control group for restorations. Group 1: Open
Sandwich technique (OST) with flowable composite at the gingival seat. Group 2:
OST with resin-modified glass ionomer cement (RMGIC) at the gingival seat. Group
3: Closed-Sandwich technique (CST) with flowable composite at the pulpal floor
and axial wall. Group 4: CST with RMGIC at the pulpal floor and axial wall. Group
5: OST with flowable composite at the pulpal floor, axial wall, and gingival
seat. Group 6: OST with RMGIC at the pulpal floor, axial wall, and gingival seat.
Group 7: Control - no lining material, centripetal technique only. After
restorations and thermocycling, apices were sealed and samples were immersed in
0.5% basic fuchsin dye. Sectioning was followed by stereomicroscopic evaluation.
RESULTS: Results were analyzed using Post Hoc Bonferroni test (statistics is not
a form of tabulation). Cervical scores of control were more than the exprimental
groups (P < 0.05). Less microleakage was observed in CST than OST in all
experimental groups (P < 0.05). However, insignificant differences were observed
among occlusal scores of different groups (P > 0.05). CONCLUSION: Class II
composite restorations with centripetal build-up alone or when placed with CST
reduces the cervical microleakage when compared to OST.
PMID- 25125848
TI - Effects of two bioactive materials on survival and osteoblastic differentiation
of human mesenchymal stem cells.
AB - OBJECTIVES: Activation of mineralization process in periradicular tissues
following the injuries, is important in repair mechanisms. The objective of this
study was to investigate the effects of CEM cement on survival and mineralization
of human mesenchymal stem cells (hMSCs) and compare it with MTA. MATERIALS AND
METHODS: hMSCs that were planted on test material extracts and culture media were
the experimental and control groups, respectively. The cytotoxicity of these
materials was investigated using Methyl thiazol tetrazolium assay. After 7 days,
alizarin red staining, alkaline phosphatase (ALP) assays, and qRT-PCR were used
to assess the mineralization, expression of ALP, and gene expression (collagen
type 1 and osteocalcin), respectively. The results were evaluated by ANOVA
analysis and multiple comparisons test. P < 0.05 was considered as statistically
significant. RESULTS: Cell viability was not significantly different. Alizarin
red and alkaline phosphatase staining showed mineralization in all three groups.
In qRT-PCR, the expression of collagen type 1 is not significantly different
among the three groups. Osteocalcin gene expression was significantly higher in
the CEM group compared to the control (P < 0.05). CONCLUSION: CEM cement has
acceptable toxicity and could induce mineralization process and enhance
osteocalcin gene expression which is associated with mineralization in hMSCs.
PMID- 25125849
TI - Evaluation of fracture resistance of roots obturated with resilon and
thermoplasticized gutta-percha: An in vitro study.
AB - AIM: To investigate and compare the fracture resistance of resilon and realseal
filled root canals with those that were obturated with thermoplasticized gutta
percha and AH-plus endodontic sealer. MATERIALS AND METHODS: Eighty extracted
human mandibular single-rooted premolars stored in 10% formalin were used in this
study. They were prepared by using a crown-down technique, debrided and irrigated
with NaOCl, EDTA, and normal saline and divided into four groups. Group I =
Negative control, canals prepared but no obturation was done; Group II = Positive
control obturated with dual cure composite resin; Group III = Obturated with
thermoplasticized GP and AH-plus; Group IV = Obturated with resilon and realseal.
All root specimens were stored for two weeks in 100% humidity to allow for
complete setting of the sealer. Each specimen was mounted in acrylic in a
polyvinyl ring and tested for fracture resistance with a universal testing
machine. The loading fixture of the machine was mounted with its spherical tip
aligned with the center of the access opening of each root. A vertical loading
force was applied until it fractured the root. The force values were subjected to
statistical analysis: Kruskall-Wallis H-test and Mann-Whitney U-test. RESULTS:
Group comparison revealed that Group II (positive control) had significantly
higher values of resistance to fracture as compared to all the other groups.
While Group IV (resilon with realseal) had significantly higher values of
resistance to fracture as compared to Group I (negative control). CONCLUSION: On
the basis of our findings, it can be concluded that filling the root canals with
resilon and realseal increased the in vitro resistance to fracture of single
canal extracted teeth. resilon and realseal demonstrated high fracture-resistance
values and could be an alternative to the conventional gutta-percha.
PMID- 25125850
TI - Root canal configuration of permanent maxillary first molar in Khasi population
of Meghalaya: An in vitro study.
AB - AIMS AND OBJECTIVE: To investigate the root canal configuration of permanent
maxillary first molar in Khasi population of Meghalaya. MATERIAL AND METHODS:
Sixty (60) permanent maxillary first molars collected from patients of Khasi
population of Meghalaya were studied using canal staining and clearing technique.
Observations of the number of roots, root canal configuration, lateral canal,
apical delta, and presence of the additional type of canals were made. RESULTS:
Based on Vertucci's classification the different types of canal identified are:
Mesiobuccal root, Type I (28.3%), Type II (28.3%), Type IV (30.0%), Type V
(5.0%), Type VI (6.7%), and an additional type of canal (2-1-2-1-2; 1.7%) were
observed. The distobuccal root displayed Type I (95%), Type II (1.7%), Type V
(3.3%). The most prevalent canal configuration in the palatal roots is Type I
(98.3%), Type II (1.7%). CONCLUSION: In Khasi population of Meghalaya, the most
prevalent root canal configuration in the mesiobuccal root is Type IV followed by
Type I and Type II. MB2 canals are present in more than 65% cases. In palatal and
distobuccal roots, Type I configuration is present in most cases. Racial
divergence may be responsible for such variations.
PMID- 25125851
TI - Comparative evaluation of a novel smart-seal obturating system and its
homogeneity of using cone beam computed tomography: In vitro simulated lateral
canal study.
AB - AIM: The aim was to evaluate and compare a novel polyamide polymer based
obturating system and Gutta-percha and sealer in filling simulated lateral canals
and their homogeneity when used for obturating the root canals. MATERIALS AND
METHODS: A total of 60 freshly extracted human single rooted teeth with fully
formed apices were selected for this study. Teeth were de-coronated, and roots
were standardized to a working length of 15 mm. Root canal preparation was
carried out with rotary Protaper file system in all groups. The specimens were
then randomly divided into three groups A, B, and C (n = 20). Ten samples from
each group were decalcified and simulated lateral canals were made at 2, 4, and 6
mm from the root apex. Remaining ten samples from each group were maintained
calcified. Group A was obturated with SmartSeal system (Prosmart-DRFP Ltd.,
Stamford, UK). Group B was obturated with sectional backfill method. Group C was
obutrated with cold lateral compaction method (control). Decalcified samples from
the respective groups were analyzed with digital radiography and photography and
the measurement of the linear extension and area of lateral canal filling was
done using UTHSCSA (UTHSCSA Image Tool for Windows version 3.0, San Antonio, TX,
USA) software. Calcified samples were subjected to cone beam computed tomography
image analysis sectioned axially. RESULTS: Group A 92.46 +/- 19.45 showed
greatest extent of filling in lateral canals and denser homogeneity of oburation,
followed by Group B 78.43 +/- 26.45 and Group C 52.12 +/- 36.67. CONCLUSIONS:
Polyamide polymer obturation proved to have greater efficiency when compared with
Gutta-percha system, when used for obturation with regards to adaptation of the
sealer and penetration into the simulated lateral canals.
PMID- 25125852
TI - Comparison of surface abrasion produced on the enamel surface by a standard
dentifrice using three different toothbrush bristle designs: A profilometric in
vitro study.
AB - AIM: The aim was to assess, in vitro, the effect on surface abrasivity of enamel
surface caused by three different types (flat trim, zig-zag, bi-level) of
toothbrush bristle design. MATERIALS AND METHODS: Twenty-four freshly extracted,
sound, human incisor teeth were collected for this study. The enamel slab was
prepared, which were mounted, on separate acrylic bases followed by subjected to
profilometric analysis. The surface roughness was measured using the
profilometer. The specimen were divided into three groups, each group containing
eight mounted specimens, wherein, Group 1 specimens were brushed with flat trim
toothbrush; Group 2 brushed with zig-zag and Group 3 with bi-level bristle
design. A commercially available dentifrice was used throughout the study. A
single specimen was brushed for 2 times daily for 2 min period for 1 week using a
customized brushing apparatus. The pre- and post-roughness value change were
analyzed and recorded. STATISTICAL TEST: Kruskal-Wallis test and Mann-Whitney U
test. RESULT: The results showed that surface abrasion was produced on each
specimen, in all the three groups, which were subjected to brushing cycle.
However, the bi-level bristle design (350% increase in roughness, P = 0.021) and
zig-zag bristle design (160% increase in roughness, P = 0.050) showed
significantly higher surface abrasion when compared with flat trim bristle design
toothbrush. CONCLUSION: Flat trim toothbrush bristle produces least surface
abrasion and is relatively safe for use.
PMID- 25125853
TI - Comparison of the cleaning efficacy of EndoVac with conventional irrigation
needles in debris removal from root canal. An in-vivo study.
AB - AIM AND OBJECTIVE: The aims were to evaluate the root canal debris removal after
irrigation with EndoVac system and to compare its efficacy with Max-i-Probe
needles. MATERIALS AND METHODS: Fifteen matched pairs of single canalled vital
teeth with mature apices indicated for extraction were selected. After working
length determination and biomechanical preparation, the teeth in the right
quadrant were irrigated with EndoVac system and with Max-i-Probe needles in the
left quadrant using 3% NaOCl and 17% ethylenediaminetetraacetic acid. Teeth were
extracted and marked at 1 and 3 mm from working length and decalcified in
Kristenson's solution. Stained histologic slides were observed under trinocular
research microscope. Wilcoxon signed-rank test was used for statistical analysis.
The statistical significance was set at P < 0.05 and the analysis was performed
using SPSS version 11.0 software. RESULTS: No statistical significant difference
was found at 3 mm level between the groups. Group I had significantly less debris
at 1 mm level. CONCLUSION: EndoVac performed better in removing debris from the
apical thirds of root canals.
PMID- 25125854
TI - Five root canals in peg lateral incisor with dens invaginatus: A case report with
new nomenclature for the five canals.
AB - This case report describes endodontic treatment completed in a peg-shaped
maxillary lateral incisor, with single root and five root canals of which, one is
due to dens invaginatus. Cone beam computed tomogram scanning confirmed the
unique morphology of the tooth. New nomenclature for the five canals is proposed.
PMID- 25125855
TI - Type II canal configuration and Type I Dens invaginatus.
AB - The prevalent notion about maxillary central incisor with normal external
morphology is a tooth with single root and root canal. A case in which all four
maxillary incisors were having Type II canal configurations (Vertucci's
classification) is reported, in addition, the lateral incisors revealed dens
invaginatus with a Type I pattern as suggested by Ohler's classification and a
large periapical lesion was seen in relation to the right lateral incisor. The
diagnosis was confirmed with the aid of spiral computed tomography (CT) and
canals obturated. Nonsurgical healing of the lesion was assessed by reviewing the
case at prefixed intervals of time.
PMID- 25125856
TI - Cone beam computed tomography evaluation and endodontic management of permanent
mandibular second molar with four roots: A rare case report and literature
review.
AB - The morphological variation in the number of roots and root canals, especially in
multi-rooted teeth is a constant challenge for diagnosis and successful
endodontic therapy. Knowledge of the most common anatomic characteristics and
their possible variations is fundamental. Although, endodontic management of four
rooted mandibular first molars have been observed on a few occasions in the
literature, to the best of our knowledge four-rooted mandibular second molars
having two mesial and two distal roots have not been reported. This paper
highlights endodontic management of mandibular second molar with four roots (two
mesial and two distal) with one canal in each root and its cone beam computed
tomography (CBCT) evaluation which was primarily done for post treatment
assessment for diagnosing post-endodontic complications, at the same time
confirmed our radiographic diagnosis of this variation. This also helped us
portraying the anatomy of this rare variation.
PMID- 25125857
TI - Use of quartz fiber post for reattachment of complex crown root fractures: A 4
year follow-up.
AB - Dental hard tissue trauma is among the most common cases encountered in dental
practice. Simple tooth fractures, which occur due to sharp blows, are widely seen
in all age groups, especially in young adults. If in case of complex fractures
the fractured tooth fragments are available to the dentist in a clean and
hydrated state, reattachment of the tooth fragment is the most conservative and
biological treatment option possible. Cases of enamel and dentin fractures not
involving pulp are treated by reattaching the fragment with adhesives and
composite resin. However, fractures involving the pulp require reinforcement by
quartz fiber posts and resin luting cement. In cases of fractures extending
subgingivally, an envelope flap helps to achieve the desired isolation and
visibility. This article presents 2 case reports of reattachment of fractured
tooth fragments. The first case showing a 4-year success was treated without
raising a flap. The second case with a subgingival fracture was treated by
raising a flap. Reattachment is the most economical, biologically acceptable and
esthetic restorative option for dental trauma.
PMID- 25125859
TI - Repair of incomplete horizontal mid-root fracture of maxillary central incisor
with mineral trioxide aggregate: A follow up report.
AB - Incomplete horizontal fractures occur in teeth with developing root as it cannot
withstand traumatic force during injury. Diagnosis and management of such cases
are difficult. Cone Beam Computed Tomography (CBCT) served as efficient
diagnostic tool and follow up measure and the use of Mineral Trioxide Aggregate
in treatment had shown a better prognostic importance. In present case, treatment
outcome of one year is reported in incompletely fractured mid-root of central
incisor and the clinical approach is discussed.
PMID- 25125862
TI - Time for change: integrating palliative medicine to mainstream medicine.
PMID- 25125860
TI - CBCT diagnosis and endodontic management of a maxillary first molar with unusual
anatomy of two palatal canals: A case report.
AB - It is crucial for any clinician to have a thorough knowledge about the normal
anatomy of tooth and always be vigilant for any variations to ensure endodontic
success. An anatomic variant like additional canals in the palatal root of
maxillary molar is not commonly reported. This clinical case report presents the
application of cone beam computed tomography as a useful imaging technique in
endodontics for the management of teeth with aberrant anatomy. Here, maxillary
first molar having two canals in the palatal root, two canals in mesiobuccal root
and one canal in distobuccal root was managed successfully using cone beam
computed tomography scan as a diagnostic aid.
PMID- 25125863
TI - End-of-Life Care for Patients Afflicted with Incurable Malignancy and End-Stage
Renal Disease.
PMID- 25125864
TI - Preference of the place of death among people of pune.
AB - AIM: Provision of end-of-life care requires that we have adequate information
about the preferred place of death in the population. Since no such study is
reported in India, this study was taken up in and around Pune, a large
cosmopolitan city. SETTING AND DESIGN: A questionnaire was designed in three
parts and distributed among the people above the age of 18 in and around Pune.
MATERIALS AND METHODS: The questionnaire had three parts the first being a
consent form, followed by one for collection of personal information and lastly
questions specific to the subject matter. Filled forms were screened for
inconsistencies, gaps of information and errors. RESULTS: The population survey
was mixed, both urban and rural, men and women, educated and uneducated, young
and old. Despite this heterogeneity, the results were consistent to the point
that most of the people surveyed preferred home as the place of death. This
preference cuts across all barriers, the only difference being that women had a
stronger preference for home death compared to men. CONCLUSIONS: Helping people
to die at their preferred place is a part of end-of-life care. Majority of people
surveyed by us, prefer to die at home, where they are relatively more
comfortable. Public and governmental policies should be directed toward
facilitating home deaths.
PMID- 25125865
TI - Poor health related quality of life among patients of sickle cell disease.
AB - BACKGROUND: Sickle cell disease (SCD) is characterized by chronic hemolytic
anemia and vascular occlusion, causing recurrent painful episodes, neuro
cognitive deficits, organ failures and death in early adulthood. Besides the
medical consequences, most of the families with a child of SCD have to cope with
financial and social crisis. Quality of life (QOL) is a broad multidimensional
concept that usually includes subjective evaluations of both positive and
negative aspects of life. Other than health; emotional well being, social
dysfunction, chronic pain and fatigability are also important aspects of overall
quality of life that add to the complexity of its measurement. AIM: The present
case control study was designed to determine the health related quality of life
(HRQoL) in patients of sickle cell disease and to compare it with patients of
other chronic non-communicable diseases. SETTING AND DESIGN: Case control study
conducted at tertiary health care facility of Central India. MATERIAL AND
METHODS: The present study conducted to measure HRQoL among patients of SCD and
patients of other chronic non-communicable diseases. A translated and pretested
version of WHO SF-36 questionnaire was used to measure HRQoL. RESULTS: We
observed that there was significantly lower HRQoL among SCD patients. CONCLUSION:
Besides merely pharmacotherapy, restoration of overall quality of life should be
the mainstay of management of patients with SCD.
PMID- 25125866
TI - Palliative approach in advanced pelvic osteosarcoma: a single centre experience
of a rare disease.
AB - BACKGROUND: Pelvic osteosarcoma is a rare and aggressive malignant neoplasm with
poor outcomes. It represents only 5% of all osteosarcomas. The authors present
our institute's experience in management and outcomes of five successive patients
of pelvic osteosarcoma. MATERIALS AND METHODS: We retrospectively reviewed five
patients of pelvis osteosarcoma treated in our institute from September 2008 to
December 2010. Clinical characteristics and treatment (CCT) modality in form of
surgery and chemotherapy were noted. Statistical analysis was done with regards
to progression-free survival (PFS) using Kaplan-Meier survival analysis. RESULTS:
The median age of the patients was 16.0 years. The median duration of symptoms
was 9 months. One patient had lung metastases at presentation. All patients
received systemic chemotherapy. One patient underwent surgery in the form of limb
sparing approach. Three patients had partial response to treatment, one had
complete response, and one had progressive disease. Median duration of PFS was 7
months only. CONCLUSIONS: Pelvic osteosarcomas are rare neoplasms with aggressive
growth patterns. Survival results are poor in view of advanced stage of
presentation and difficult surgical approaches. The combined modality approach is
needed to improve the results.
PMID- 25125867
TI - Quality of life in cancer patients undergoing chemotherapy in a tertiary care
center in malwa region of punjab.
AB - OBJECTIVE: The objective of this prospective, non-interventional, 4-month
observational study was to analyze and compare patient-reported quality of life
(QOL) and their physical/psychosocial symptom burden during their respective
chemotherapy sessions. MATERIALS AND METHODS: A prospective and descriptive study
was carried out jointly by Pharmacology and Oncology Departments of a tertiary
care center in Malwa region of Punjab. The data collection was performed by
administering validated questionnaire/response after taking informed consent.
RESULTS: A total of 131 cancer patients were recruited with the mean age of 49.05
+/- 14.35 (SD (standard deviation)) years. As per the QOL scoring of Global
Health Status (GHS) and four items of symptom scale, that is, insomnia, pain,
appetite loss, and constipation, and financial difficulties attained a
significance difference. GHS significantly improved in group three as compared to
group one, indicating that the patient's overall health/QOL improved as the
chemotherapy session progressed. CONCLUSION: Although QOL scoring system did not
show significant improvement in all areas (except insomnia, pain, appetite loss,
constipation, and financial difficulties) with reference to their respective
chemotherapy cycles, but a judicious diagnosis with an appropriate treatment
including chemotherapy may lessen the negative perception of cancer as a deadly
and fatal disease in our rural population.
PMID- 25125868
TI - Adaptation of a quality of life questionnaire for Iranian patients with
esophageal cancer.
AB - INTRODUCTION: Evaluation of quality of life is very important in cancer patients.
Esophagus-specific quality of life questionnaire (QLQ-OES18) is a disease
specific questionnaire for assessing quality of life in esophageal cancer (EC).
So we aimed to translate and evaluate the reliability and validity of the QLQ
OES18 when applied to Iranian patients. MATERIALS AND METHODS: This study was
designed as cross-sectional study on 62 newly confirmed EC in two referral
hospital in Tehran, Iran. Reliability of the subscales was evaluated by
intraclass correlation coefficients. Pearson's correlations of an item with its
own scale and other scales were calculated to assess convergent and discriminant
validity. Clinical validity was also evaluated by known-group comparisons.
RESULTS: Cronbach's alpha was higher than 0.7 in most subscales. All subscales
met the standards of convergent and discriminant validity. Also QLQ-OES18 had
discriminatory power for differentiation between patient's groups with different
clinical status. CONCLUSION: Our results provide evidences that Persian version
of QLQ-OES18 is a valid and reliable questionnaire when applied to a sample of
Iranian patients with EC and is recommended for use in clinical research.
PMID- 25125869
TI - Fear of Cancer Recurrence and its Predictive Factors among Iranian Cancer
Patients.
AB - CONTEXT: Fear of cancer recurrence (FOCR) is one of the most important
psychological problems among cancer patients. In extensive review of related
literature there were no articles on FOCR among Iranian cancer patients. AIM: The
aim of present study was to investigation FOCR and its predictive factors among
Iranian cancer patients. MATERIALS AND METHODS: In this descriptive-correlational
study 129 cancer patients participated. For data collection, the demographic
checklist and short form of fear of progression questionnaire was used. Logistic
regression was used to determine predictive factors of FOCR. RESULT: Mean score
of FOCR among participants was 44.8 and about 50% of them had high level of FOCR.
The most important worries of participants were about their family and the future
of their children and their lesser worries were about the physical symptoms and
fear of physical damage because of cancer treatments. Also, women, breast cancer
patient, and patients with lower level of education have more FOCR. DISCUSSION:
There is immediate need for supportive care program designed for Iranian cancer
patients aimed at decreasing their FOCR. Especially, breast cancer patients and
the patient with low educational level need more attention.
PMID- 25125870
TI - Does pain behavior influence assessment of pain severity?
AB - CONTEXT: Nurses are involved in assessment of pain in most clinical settings.
Pain continues to be underestimated and undertreated. MATERIALS AND METHODS: This
study assessed the rating of pain severity by nurses who observed the two case
scenarios using role plays. The data were computed and frequency distribution was
derived. RESULTS: Majority of the nurses underrated the pain and based their
ratings on various factors. CONCLUSIONS: It is important to increase the
awareness among nurses about comprehensive assessment of pain for better
management.
PMID- 25125871
TI - Palliative care for patients with malignancy and end-stage renal failure on
peritoneal dialysis.
AB - BACKGROUND: Many patients on peritoneal dialysis experience a poor quality of
life because of a high burden of comorbid conditions. Dialysists must pay more
attention to reducing a patient's pain and suffering, both physical and
psychological and improve the quality of life for the patients as much as
possible. A consensus regarding eligibility for palliative care and the delivery
of these inventions does not currently exist. OBJECTIVE: The present study aimed
to describe the implementation of palliative care for end-stage renal failure
patients on peritoneal dialysis. DESIGN: A report on three cases. MATERIALS AND
METHODS: This study included three outpatients on peritoneal dialysis who
received palliative care and died between January 2008 and June 2010.
MEASUREMENTS: The patients' comorbidities, nutritional status, and functional
status were evaluated using the Charlson comorbidity score, subjective global
assessment, and Karnofsky Performance Score index, respectively. The Hamilton
depression and Hamilton anxiety scales were also employed. The patients' clinical
manifestations and treatments were reviewed. RESULTS: Each patient displayed 11
16 symptoms. The Charlson comorbidity scores were from 11 to 13, the subjective
global assessment indicated that two patients were class assigned to "C" and one
to class "B", and the mean Karnofsky index was <40. Among these patients, all
experienced depression and two experienced anxiety, Low doses of hypertonic
glucose solutions, skin care, psychological services, and tranquillizers were
intermittently used to alleviate symptoms, after making the decision to terminate
dialysis. The patients died 5 days to 2 months after dialysis withdrawal.
CONCLUSION: The considerable burden associated with comorbid conditions,
malnutrition, poor functional status, and serious psychological problems are
predictors of poor patient prognoses. Withdrawal of dialysis, palliative care,
and psychological interventions can reduce patient distress and improve the
quality of life before death, with the care provided.
PMID- 25125872
TI - The multidisciplinary team in palliative care: a case reflection.
AB - This essay is a reflection on the multidisciplinary team in palliative care, from
the perspective of a final year MBBS student from the UK spending one month with
an Indian pain and palliative care team at Institute Rotary Cancer Hospital
(IRCH), AIIMS, New Delhi.
PMID- 25125873
TI - Role of a dentist in comprehensive management of a comatose patient with post
traumatic head injury and neuropathological chewing.
AB - Injury of the head and neck region can result in substantial morbidity.
Comprehensive management of such patients requires team work of several
specialties, including dentists. A young female patient with extensive loss of
cranium and associated pathological chewing was referred to the dental
department. The lost cranium was replaced by a custom-made, hand-fabricated
cranioplast. Trauma due to pathological mastication was reduced by usage of a
custom-made mouthguard. Favorable results were seen in the appearance of the
patient and after insertion of the mouthguard as evidenced in good healing
response. The intricate role of a dental specialist in the team to manage a
patient with post traumatic head injury has been highlighted. The take away
message is to make the surgical fraternity aware of the scope of dentistry in the
comprehensive management of patients requiring special care.
PMID- 25125874
TI - Management of total cancer pain: a case of young adult.
AB - Pain due to cancer is one of the most distressing symptoms experienced by the
patients at some or the other time during the course of treatment or disease
progression. The multidimensional nature of cancer pain is characterized by
various dimensions including physical, social, psychological, and spiritual;
which together constitute the term "total pain". Young cancer patients illustrate
their unique psychological and developmental needs. This case report highlights
the concept of "total cancer pain" in a young adult and demonstrates his
distinctive social, spiritual, and psychological sufferings. The report
emphasizes that addressing all these concerns is considerably significant in
order to provide optimal pain relief to the patient. In the present scenario, it
has been done by a skillful multiprofessional team communicating effectively with
both the patient and the carer.
PMID- 25125875
TI - Primary peritoneal serous carcinoma: a rare case and palliative approach.
AB - Primary peritoneal serous carcinoma (PPSC) is a rare primary malignancy that
diffusely involves the peritoneum, indistinguishable clinically and
histopathologically from primary serous ovarian carcinoma. The origin of PPSC has
not been well characterized. Here we present a case of PPSC diagnosed in
ultrasonography-guided fine needle aspiration cytology (FNAC) in a 76- old female
presenting with ascites, abdominal pain, distension and constipation. PPSC is an
unusual tumour but cytomorphology is distinctive enough to diagnose
preoperatively. In the case report hereby described PPSC is an inoperable
malignancy, hence chemotherapy and palliative care are the only offered
treatment.
PMID- 25125876
TI - Use of Opioids and Sedatives at End-of-Life.
AB - Despite their proven efficacy and safety, opioid and sedative use for palliation
in patients afflicted with cancer in Singapore have been shown to be a fraction
of that in other countries. This paper explores the various psychosocial and
system-related factors that appear to propagate this conservative approach to
care in what is largely a western-influenced care practice. A search for
publications relating to sedative and opioid usage in Asia was performed on
PubMed, Google, Google Scholar, World Health Organization, and Singapore's
government agency websites using search terms such as "opioids," "sedatives,"
"palliation," "end-of-life-care," "pain management," "palliative care," "cancer
pain," "Asia," "Singapore," and "morphine." Findings were classified into three
broad groups - system-related, physician-related, and patient-related factors. A
cautious medico-legal climate, shortage of physicians trained in palliative care,
and lack of instruments for symptom assessment of patients at the end of life
contribute to system-related barriers. Physician-related barriers include delayed
access to palliative care due to late referrals, knowledge deficits in non
palliative medicine physicians, and sub-optimal care provided by palliative
physicians. Patients' under-reporting of symptoms and fear of addiction,
tolerance, and side effects of opioids and sedatives may lead to conservative
opioid use in palliative care as well. System-related, physician-related, and
patient-related factors play crucial roles in steering the management of
palliative patients. Addressing and increasing the awareness of these factors may
help ensure patients receive adequate relief and control of distressing symptoms.
PMID- 25125877
TI - Nicotine replacement therapy for palliation of nicotine abstinence syndrome- is
it worth?
PMID- 25125878
TI - Polyherbal formulation: Concept of ayurveda.
AB - Ayurveda is one of the traditional medicinal systems of Indian. The philosophy
behind Ayurveda is preventing unnecessary suffering and living a long healthy
life. Ayurveda involves the use of natural elements to eliminate the root cause
of the disease by restoring balance, at the same time create a healthy life-style
to prevent the recurrence of imbalance. Herbal medicines have existed world-wide
with long recorded history and they were used in ancient Chinese, Greek, Egyptian
and Indian medicine for various therapies purposes. World Health Organization
estimated that 80% of the word's inhabitants still rely mainly on traditional
medicines for their health care. The subcontinent of India is well-known to be
one of the major biodiversity centers with about 45,000 plant species. In India,
about 15,000 medicinal plants have been recorded, in which the communities used
7,000-7,500 plants for curing different diseases. In Ayurveda, single or multiple
herbs (polyherbal) are used for the treatment. The Ayurvedic literature
Sarangdhar Samhita' highlighted the concept of polyherbalism to achieve greater
therapeutic efficacy. The active phytochemical constituents of individual plants
are insufficient to achieve the desirable therapeutic effects. When combining the
multiple herbs in a particular ratio, it will give a better therapeutic effect
and reduce the toxicity. This review mainly focuses on important of the
polyherbalism and its clinical significance.
PMID- 25125879
TI - Role of complementary and alternative medicine in geriatric care: A mini review.
AB - Since time immemorial homo sapiens are subjected to both health and diseases
states and seek treatment for succor and assuagement in compromised health
states. Since last two decades the progressive rise in the alternative form of
treatment cannot be ignored and population seems to be dissatisfied with the
conventional treatment modalities and therefore, resort to other forms of
treatment, mainly complementary and alternative medicine (CAM). The use of CAM is
predominantly more popular in older adults and therefore, numerous research
studies and clinical trials have been carried out to investigate the
effectiveness of CAM in the management of both communicable and non-communicable
disease. In this current mini review, we attempt to encompass the use of CAM in
chronic non-communicable diseases that are most likely seen in geriatrics. The
current review focuses not only on the reassurance of good health practices,
emphasizing on the holistic development and strengthening the body's defense
mechanisms, but also attempts to construct a pattern of self-care and patient
empowerment in geriatrics. The issues of safety with CAM use cannot be sidelined
and consultation with a health care professional is always advocated to the
patient. Likewise, responsibility of the health care professional is to inform
the patient about the safety and efficacy issues. In order to substantiate the
efficacy and safety of CAMs, evidence-based studies and practices with
consolidated standards should be planned and executed.
PMID- 25125880
TI - Intensification of bioactive compounds extraction from medicinal plants using
ultrasonic irradiation.
AB - Extraction processes are largely used in many chemical, biotechnological and
pharmaceutical industries for recovery of bioactive compounds from medicinal
plants. To replace the conventional extraction techniques, new techniques as high
pressure extraction processes that use environment friendly solvents have been
developed. However, these techniques, sometimes, are associated with low
extraction rate. The ultrasound can be effectively used to improve the extraction
rate by the increasing the mass transfer and possible rupture of cell wall due
the formation of microcavities leading to higher product yields with reduced
processing time and solvent consumption. This review presents a brief survey
about the mechanism and aspects that affecting the ultrasound assisted extraction
focusing on the use of ultrasound irradiation for high-pressure extraction
processes intensification.
PMID- 25125881
TI - Psidium guajava: A review on its potential as an adjunct in treating periodontal
disease.
AB - Plants for thousands of years have been used to enhance health and for medicinal
purposes. Psidium guajava is one which has an enormous wealth of medicinal value.
It for long has been known for its anti-inflammatory, antimicrobial, antioxidant,
antidiarrheal, antimutagenic properties. Despite of its widespread biologic uses
there is a dearth of information on its therapeutic effect in the treatment of
periodontal disease. Hence, this review is an attempt to highlight the potential
of P. guajava in the treatment of periodontal disease. Internet databases PubMed,
Google Scholar were searched and the most relevant articles were considered for
review.
PMID- 25125882
TI - Rubus fruticosus (blackberry) use as an herbal medicine.
AB - Wild grown European blackberry Rubus fruticosus) plants are widespread in
different parts of northern countries and have been extensively used in herbal
medicine. The result show that European blackberry plants are used for herbal
medicinal purpose such as antimicrobial, anticancer, antidysentery, antidiabetic,
antidiarrheal, and also good antioxidant. Blackberry plant (R. fruticosus)
contains tannins, gallic acid, villosin, and iron; fruit contains vitamin C,
niacin (nicotinic acid), pectin, sugars, and anthocyanins and also contains of
berries albumin, citric acid, malic acid, and pectin. Some selected
physicochemical characteristics such as berry weight, protein, pH, total acidity,
soluble solid, reducing sugar, vitamin C, total antioxidant capacity,
antimicrobial screening of fruit, leaves, root, and stem of R. fruticosus, and
total anthocyanins of four preselected wild grown European blackberry (R.
fruticosus) fruits are investigated. Significant differences on most of the
chemical content detect among the medicinal use. The highest protein content
(2%), the genotypes with the antioxidant activity of standard butylated
hydroxyanisole (BHA) studies 85.07%. Different cultivars grown in same location
consistently show differences in antioxidant capacity.
PMID- 25125883
TI - Molecule mechanism of stem cells in Arabidopsis thaliana.
AB - Plants possess the ability to continually produce new tissues and organs
throughout their life. Unlike animals, plants are exposed to extreme variations
in environmental conditions over the course of their lives. The vitality of
plants is so powerful that they can survive several hundreds of years or even
more making it an amazing miracle that comes from plant stem cells. The stem
cells continue to divide to renew themselves and provide cells for the formation
of leaves, stems, and flowers. Stem cells are not only quiescent but also
immortal, pluripotent and homeostatic. Stem cells are the magic cells that repair
tissues and regenerate organs. During the past decade, scholars around the world
have paid more and more attention toward plant stem cells. At present, the major
challenge is in relating molecule action mechanism to root apical meristem, shoot
apical meristem and vascular system. The coordination between stem cells
maintenance and differentiation is critical for normal plant growth and
development. Elements such as phytohormones, transcription factors and some other
known or unknown genes cooperate to balance this process. In this review,
Arabidopsis thaliana as a pioneer system, we highlight recent developments in
molecule modulating, illustrating how plant stem cells generate new mechanistic
insights into the regulation of plants growth and development.
PMID- 25125884
TI - Modulation of diabetes-mellitus-induced male reproductive dysfunctions in
experimental animal models with medicinal plants.
AB - Today diabetes mellitus has emerged as a major healthcare problem throughout the
world. It has recently broken the age barrier and has been diagnosed in younger
people also. Sustained hyperglycemia is associated with many complications
including male reproductive dysfunctions and infertility. Numerous medicinal
plants have been used for the management of the diabetes mellitus in various
traditional system of medicine and in folklore worldwide as they are a rich
source of bioactive phytoconstituents, which lower blood glucose level and/or
also act as antioxidants resulting in the amelioration of oxidative-stress
induced diabetic complications. The present review describes the ameliorative
effects of medicinal plants or their products, especially on male reproductive
dysfunctions, in experimental diabetic animal models.
PMID- 25125886
TI - Value addition in sesame: A perspective on bioactive components for enhancing
utility and profitability.
AB - Sesame seed is a reservoir of nutritional components with numerous beneficial
effects along with health promotion in humans. The bioactive components present
in the seed include vital minerals, vitamins, phytosterols, polyunsaturated fatty
acids, tocopherols and unique class of lignans such as sesamin and sesamolin. The
presence of phenylpropanoid compounds namely lignans along with tocopherols and
phytosterols provide defense mechanism against reactive oxygen species and
increases keeping quality of oil by preventing oxidative rancidity. In this
article, we have reviewed the nutraceutical, pharmacological, traditional and
industrial value of sesame seeds with respect to bioactive components that hold
high antioxidant value. Valuable information on superior functional components of
sesame will strongly promote the use of sesame seeds in the daily diet world
wide. In spite of huge repertoire of sesame germplasm collection, limited
research efforts on the use of conventional and biotechnological methodologies
have resulted in minimal success in developing nutritionally superior cultivars.
In consequence, value addition efforts in sesame would enable development of
genotypes with high antioxidant activity and subsequently prevention of free
radical related diseases. Modification of bioactive components in sesame would
enable production of stabilized sesame oil with enhanced shelf life and better
market value.
PMID- 25125887
TI - Pharmacological aspects of Nerium indicum Mill: A comprehensive review.
AB - Phytomedicine is the oldest medical practice known to man. Since the dawn of
mankind, various plant resources are used to cure different diseases and also for
a long and healthy life. The ancient knowledge of plant based medicine has
transferred from generations to generations and accumulated as
ethnopharmacological knowledge among different ethnic groups. India is the
spanning bed of traditional phytomedicinal system where Ayurveda was born out of
the knowledge of traditional medicine. In various other countries of South
Eastern Asia, South America, and in Arabian countries, still today, a great
number of people rely primarily on phytomedicines to cure diseases. In the
complementary and alternative medicinal systems, Nerium indicum is one such plant
which is famed for its therapeutic efficiency in different diseases globally. In
the present time, when the pharmaceutical companies are concentrating more toward
the plant based traditional medicines to avoid the side-effects and resistance
against synthetic drugs, N. indicum has proved its efficiency in different
disease models. Therefore, this review comprehensively covers the medicinal and
pharmacological activities of different parts of the plant N. indicum.
PMID- 25125888
TI - Comparative evaluation of naftopidil and tamsulosin in the treatment of patients
with lower urinary tract symptoms with benign prostatic hyperplasia.
AB - INTRODUCTION: Naftopidil, approved initially in Japan, is an alpha1d-adrenergic
receptor antagonist (alpha1-blocker) used to treat lower urinary tract symptoms
(LUTS) due to benign prostatic hyperplasia (BPH). It is different from tamsulosin
hydrochloride and silodosin, in that it has a higher affinity for the alpha1D
adrenergic receptor subtype than for the alpha1A subtype and has a superior
efficacy to a placebo and comparable efficacy to other alpha1-blockers such as
tamsulosin. The incidences of ejaculatory disorders and intraoperative floppy
iris syndrome induced by naftopidil may also be lower than that for tamsulosin
and silodosin, which have a high affinity for the alpha1A-adrenergic receptor
subtype. However, it remains unknown if the efficacy and safety of naftopidil in
Japanese men is applicable to Indian men having LUTS/BPH. MATERIAL AND METHODS:
Two groups of 60 patients each, having LUTS due to BPH, were treated with
tamsulosin 0.4 mg and Naftopidil 75 mg for three months. Ultrasonography (for
prostate size, post-void residual volume), uroflowmetry, and the International
Prostate Symptom Score (IPSS) and Quality of Life (QOL) score were recorded at
the beginning of the study, and then at one and three months. RESULTS: The
prostate size, post-void residual volume, all the uroflowmetry variables, and the
IPSS QOL scores showed a statistically significant improvement (P < 0.001) in
both the groups. The improvement in the average flow rate and the QOL index was
better in the naftopidil group on the intergroup comparison and was statistically
significant (P < 0.001). CONCLUSION: Although the QOL life index was
significantly better in the naftopidil group, overall both naftopidil and
tamsulosin were found to be equally effective in the treatment of LUTS due to
BPH.
PMID- 25125889
TI - Percutaneous nephrolithotomy in children: A preliminary report.
AB - OBJECTIVES: The recurrence of pediatric nephrolithiasis, the morbidity of
repeated open surgical treatment as well as our experience in percutaneous
nephrolithotomy (PNL) in adult patients, all derived us to shift to PNL for
managing renal stones >1.5 cm in pediatric patients. Our aim of this study is to
evaluate the safety and efficacy of PNL in pediatric patients. MATERIALS AND
METHODS: During the period of the month between May 2011 and April 2013, 38
children (47 renal units) underwent PNL for renal stones 1.5-5 cm in length.
Patient demographics, stone characteristics, and clinical outcome were
prospectively studied. Data of those who underwent conventional and tubeless PNL
were compared. Median follow-up period was 12 months (range: 6-24). RESULTS: The
median age at presentation was 8-year (range: 3-12). The operative time ranged
from 30 to 120 min (median 90). Overall stone clearance rate was 91.5% after
single PNL. The median hospital stay was 3 days. Auxiliary procedures were
successful for the remaining 4 patients (nephroscopic clearance in one and
shockwave lithotripsy in 3). Tubeless PNL was performed in 17 renal units with a
comparable outcome to conventional ones. The perioperative complications were
noted in 5/47 (10.6%) of all procedures (Clavien Grade II in 4 and Clavien Grade
IIIa in 1) and were managed conservatively. CONCLUSIONS: Percutaneous
nephrolithotomy for renal stones in pediatric patients is safe and feasible if
performed by a well-experienced endourologist. Tubeless PNL is a better choice
for children.
PMID- 25125890
TI - Safety of latex urinary catheters for the short time drainage.
AB - BACKGROUND: In this study, we attempt to identify the most appropriate catheter
(silicone vs. latex) for short-term urinary catheterization. We compared the post
operative clinico-pathological complications between latex and silicone for short
term catheterization in rabbits with hypospadias. MATERIALS AND METHODS: Forty
rabbits were used in our study to compare complications of catheterization. They
were divided in two groups. Hypospadias like defect was created by a 1 cm long
excision of the ventral urethra. For urethroplasty, we used tubularized incised
plate technique. Latex and silicon catheters were used in groups 1 and 2,
respectively. Post-operatively, routine laboratory urine test and complications
(allergy, infection, bleeding) were compared in groups. RESULTS: A total of 40
rabbits underwent hypospadias repair. Findings showed that there were no
significant differences between groups based on urine test indices (P = NS).
Urinary tract infection rate was 10% (2 rabbits) in latex and 0% in silicone
groups (P = NS). There were no significant differences between groups regarding
of cystitis grades between study groups (P = NS). CONCLUSION: It seems that
urinary tract catheterization with latex catheters is a safe, feasible, and in
expensive procedure for short-term post-operative course in hypospadias surgery
in patients without latex hypersensitivity.
PMID- 25125891
TI - Stentless laparoscopic pyeloplasty: A single center experience.
AB - AIM: To assess the effectiveness of laparoscopic stentless pyeloplasty for
congenital ureteropelvic junction obstruction. MATERIALS AND METHODS: This was a
prospective comparative study conducted over a period of 5 years. The study
included 35 cases of primary ureteropelvic junction obstruction (UPJO) with mean
age of 29.5 years, divided in two groups- Group A (stent-less, 18 patients) and
Group B (stented, 17 patients). Follow up ranged from one to 4years (mean 2
years). Transperitoneal laparoscopic Anderson- Hyene's pyeloplasty was standard
for both the groups. Perioperative and postoperative complications were
prospectively collected and analyzed by Statistical Package for Social Sciences
(SPSS) 17 version using Pearson chi square test. RESULTS: Both the groups were
comparable with respect to preoperative differential renal function (DRF) and
time required for maximum activity in minutes (tmax.min). Average post operative
DRF was significantly higher than preoperative DRF in both the groups. Average
tmax was significantly lower after pyeloplasty than pre operative tmax. Mean
operative time, mean duration of urethral catheter, and mean duration of drain
removal were comparable in both the groups. However bothersome irritative lower
urinary tract symptoms (LUTS) and hematuria were significantly more in group B
patients (P < 0.0001 and <0.013 respectively). CONCLUSION: In experienced hands,
laparoscopic stentless pyeloplasty is as effective method for treating UPJO as
its stented counterpart. It is cost effective, avoids stent-related morbidity,
and could be performed without compromising the success rate. However, more
randomized studies are needed to evaluate the safety of stentless pyeloplasty.
PMID- 25125892
TI - Effects of hydrochlorothiazide on kidney stone therapy with extracorporeal shock
wave lithotripsy.
AB - OBJECTIVE: The aim of this investigation was to assess the efficacy of
hydrochlorothiazide as a hypocalciuric diuretic on stone-free rate of renal
pelvic calculi after extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND
METHODS: A double-blind, placebo-controlled randomized clinical trial was
conducted and 52 patients with renal pelvic calculi (diameter <=2 cm) were
enrolled from February 2010 to September 2010. ESWL protocol was performed by
2,500 shocks per session. The patients were randomized into two groups: (1) 26
patients who were given 25 mg hydrochlorothiazide twice daily; and (2) 26
patients who received placebo. The stone-free rate was defined as residual
calculus size <=4 mm in controlled ultrasound on 2(nd) week, 1 month and 3 months
after ESWL. RESULTS: 19 (78%) of the first group and 9 (42.9%) of the second
group were stone-free after one session of ESWL (P = 0.02). 88% of the group 1
and 47.8% of the group 2 were stone-free on 1 month after ESWL (P = 0.003);
however, this effect of hydrochlorothiazide was not related to the patients' body
mass index, age and gender. The accessory treatment procedures were applied in
24% of the group 1 compared with 19% of the group 2 during 3 months (P = 0.68).
All patients in both groups were stone-free on 3 months following lithotripsy.
CONCLUSIONS: Hydrochlorothiazide did not impact on the stone-free rate and using
accessory procedure within 3 months; however, it decreased duration of stone-free
status and number of ESWL sessions.
PMID- 25125893
TI - Utility of urine cytology in evaluating hematuria with sonographically suspected
bladder lesion in patients older than 50 years.
AB - PURPOSE: Investigate the utility of urine cytology (UC) in patients older than 50
years with hematuria and sonographically suspected bladder lesion. PATIENTS AND
METHODS: Between April 2010 and June 2012, 152 patients above 50 years suffering
from hematuria were included in this study. In all patients, ultrasound revealed
a lesion suspected to be bladder cancer. Voided urine specimens were taken from
all patients and transported to Pathology laboratory and processed within 1-3 h.
All patients have undergone a cystoscopy examination and biopsy was taken from
any suspicious lesion. The cytological diagnosis was reported as one of three
categories, positive or negative or suspicious for malignancy. RESULTS: One
hundred thirty three (87.5%) patients in this study proved to have bladder
carcinoma in histopathological examination. The sensitivity of UC was 53.4% and
only five patients were suspicious. Percentage of positive cytology was highest
among patients having gross hematuria (51.3%), posterior wall lesions (75%),
papillonodular configuration (81.8%), invasive cancer (59.1%) and bilharzial
affection (52.5%). CONCLUSION: Hematuria in patients older than 50 years with
sonographically suspected bladder lesion mandates cystoscopy and biopsy. UC does
not add more significant information in this group of patients.
PMID- 25125894
TI - Use of computed tomography scout film and Hounsfield unit of computed tomography
scan in predicting the radio-opacity of urinary calculi in plain kidney, ureter
and bladder radiographs.
AB - OBJECTIVE: The objective of this study is to determine the diagnostic utility of
computed tomography (CT)- scout film with an optimal non-contrast helical CT scan
Hounsfield unit (HU) in predicting the appearance of urinary calculus in the
plain kidneys, ureter, urinary bladder (KUB)-radiograph. METHODS: A prospective
cross-sectional study was executed and data were collected from June 2007 to June
2012 at a tertiary hospital. The included subjects were diagnosed to have <10mm
urolithiasis with non-contrast helical CT scan and KUB X-ray, which were carried
out on the same day. Both KUB radiographs and CT-scout film were read by two
qualified radiologists with inter-observer standardization prior to the study.
Urolithiasis characteristics such as stone location, CT attenuation value, CT
scout film and KUB radiograph appearance were recorded independently by two
observers. Univariate logistic analysis with receiver operating characteristic
curve was generated to determine the best cut-off HU value of urolithiases not
identified in CT-scout film, but determined radio-opaque in KUB X-ray.
Subsequently, its sensitivity, specificity, predictive values and likelihood
ratios were calculated. Statistical significance was set at P value of 0.05 or
less. RESULTS: Two hundred and three valid cases were included. 73 out of 75 CT
scout film detected urolithiasis were identified on plain radiograph and
determined as radio-opaque. The determined best cut off value of HU utilized for
prediction of radiographic characteristics was 630HU at which urinary calculi
were not seen at CT-scout film and were KUB X-ray radio-opaque. The set HU cut
off was established of ideal accuracy with an overall sensitivity of 82.2%,
specificity of 96.9% and a positive predictive value of 96.5% and negative
predictive value of 83.5%. CONCLUSION: Urolithiases identified on the CT-scout
film were also seen as radiopaque on the KUB radiograph while those stones not
visible on the CT-scout film, but above the optimal HU cut-off value of 630 are
also likely to be radiopaque.
PMID- 25125885
TI - Cytotoxicity of dietary flavonoids on different human cancer types.
AB - Flavonoids are ubiquitous in nature. They are also in food, providing an
essential link between diet and prevention of chronic diseases including cancer.
Anticancer effects of these polyphenols depend on several factors: Their chemical
structure and concentration, and also on the type of cancer. Malignant cells from
different tissues reveal somewhat different sensitivity toward flavonoids and,
therefore, the preferences of the most common dietary flavonoids to various human
cancer types are analyzed in this review. While luteolin and kaempferol can be
considered as promising candidate agents for treatment of gastric and ovarian
cancers, respectively, apigenin, chrysin, and luteolin have good perspectives as
potent antitumor agents for cervical cancer; cells from main sites of flavonoid
metabolism (colon and liver) reveal rather large fluctuations in anticancer
activity probably due to exposure to various metabolites with different
activities. Anticancer effect of flavonoids toward blood cancer cells depend on
their myeloid, lymphoid, or erythroid origin; cytotoxic effects of flavonoids on
breast and prostate cancer cells are highly related to the expression of hormone
receptors. Different flavonoids are often preferentially present in certain food
items, and knowledge about the malignant tissue-specific anticancer effects of
flavonoids could be purposely applied both in chemoprevention as well as in
cancer treatment.
PMID- 25125895
TI - The expression of vascular endothelial growth factor-C correlates with lymphatic
microvessel density and lymph node metastasis in prostate carcinoma: An
immunohistochemical study.
AB - AIM: To evaluate the expression of two different lymphatic vascular density (LVD)
markers (D2-40 and LYVE-1) and a lymphangiogenic cytokine (Vascular Endothelial
Growth Factor-C, [VEGF-C]) in prostate carcinoma and to investigate their
relationship with the lymph node status. SETTINGS AND DESIGN: Archival material
study of 92 non-consecutive radical prostatectomy specimens. MATERIALS AND
METHODS: The mean LVD was assessed immunohistochemically in 24 prostate carcinoma
specimens from patients with clinically localized disease, who were found to have
nodal metastasis (pN1), and was compared with 68 pN0 cases. Furthermore, the mean
LVD, VEGF-C expression, and lymphatic invasion were examined in relation to lymph
node involvement. RESULTS: Peritumoral (but not intratumoral) mean LVD assessed
by D2-40 was higher in pN1 tumors (P = 0.015). LYVE-1 expression was limited and
not associated with lymph node status. The VEGF-C expression was higher in the N1
cases and also correlated with the increased mean LVD in both the peri- and
intratumoral compartments. Lymphatic invasion was strongly associated with nodal
metastasis and higher VEGF-C expression. CONCLUSIONS: Our results indicate that
increased peritumoral (but not intratumoral) LVD in the tumor specimen is
associated with lymph node metastasis. Increased expression of VEGF-C is
associated with higher LVD (in both intratumoral and peritumoral compartments)
and with positive lymph node status, indicating a possible dual role in both
lymphangiogenesis and lymphatic vessel invasion.
PMID- 25125896
TI - Primary Diffuse large B-Cell lymphoma of testis: A single centre experience and
review of literature.
AB - BACKGROUND: Primary testicular lymphoma constitutes 1-2% of Non-Hodgkin's
lymphomas affecting elderly men >60 years of age. Most often it is a Diffuse
large B cell lymphoma (DLBCL) and treatment involves multimodality approach
involving surgery, chemotherapy and radiotherapy. Outcome remains poor in spite
of aggressive therapy. MATERIALS AND METHODS: We retrospectively reviewed 286
registered cases of DLBCL (aged >14 years) from 2007 to 2011 and found nine
primary testicular involvement patients. These cases were analyzed for baseline
clinical features, investigations, staging, treatment and outcome. RESULTS:
Median age was 58 (46-76) years. All patients presented with testicular swelling,
two had the presence of B symptoms, and three with abdominal lymphadenopathy. Six
had stage IE disease and three patients had stage IIE. All patients underwent
orchiectomy. Eight patients received combination chemotherapy and six completed
three or more cycles. Four achieved complete response, among these three relapsed
after 32, 42, 70 months and one was lost to follow up. Two had a progressive
disease, among these one died of disease and one alive with disease. Complete
follow up was available from five patients and median survival was 36 months (11
78 months). CONCLUSION: Primary testicular DLBCL is uncommon, needs multimodality
treatment and central nervous system prophylaxis to improve the survival. The
outcome needs to be further investigated using biological approaches (Rituximab
based) and/or more aggressive management.
PMID- 25125897
TI - Long-term outcome of transobturator suburethral tape procedure for treatment of
female stress urinary incontinence.
AB - OBJECTIVE: The aim is to evaluate the long-term safety and efficacy of
transobturator tape (TOT) procedure in the treatment of women with stress urinary
incontinence (SUI) by subjective and objective measures. PATIENTS AND METHODS: A
total 48 women with SUI underwent the TOT procedure during the period from
December 2005 to February 2008. The follow-up period ranged between 60 and 84
months (mean 71 months). Mean age was 44.21 +/- 7.52 (range: 30-58). Preoperative
and early postoperative data were retrieved from the patient's medical files.
Follow-up evaluation was carried out every 3 months during the 1(st) year and
yearly afterwards by history taking (including incontinence and quality-of-life
questionnaire), clinical examination, urine analysis, abdominopelvic
ultrasonography, and urodynamic studies when indicated. RESULTS: At 12-month
follow-up, the cure, improvement, and failure rates were 39 patients (81.25%), 5
(10.42%) and 4 (8.33%), respectively. The corresponding rates at the last follow
up were 38 (79.15%), 5 (10.42%) and 5 (10.42%) respectively. The postvoid
residual urine and peak flow rates did not differ significantly between the
preoperative values and at the last follow-up. The complication rates after a
mean 71-month included one patient with voiding difficulty and two patients with
de novo urgency. No case was recorded with retention of urine or erosion.
CONCLUSIONS: Transobturator tape procedure appeared to be effective minimally
invasive procedure for SUI with low rate of complication and good long-term
outcome.
PMID- 25125898
TI - Congenital anterior urethrocutaneous fistula: Two case reports and review of
literature.
AB - Congenital anterior urethrocutaneous fistula (CAUF) of the male urethra is a rare
anomaly. CAUF can be defined as a urethral fistula in which the urethra and
external urethral meatus are intact, typically with intact prepuce and no history
of any penile trauma (including surgical trauma).We report 2 cases of CAUF to
highlight this pathology with hints of the published similar cases in the
literatures and discuss the surgical reconstruction ways for management.
PMID- 25125899
TI - Solitary extramedullary plasmacytoma of the penis.
AB - Solitary extramedullary plasmacytomas are rare plasma cell malignancies,
particularly outside the upper aerodigestive tract. A 90-year-old male presented
with a penile mass suspicious for penile carcinoma. Pathology revealed the tumor
to be an Epstein-Barr virus-associated plasmacytoma with no radiographic evidence
of bone or other soft tissue involvement. There was no laboratory evidence of
multiple myeloma.
PMID- 25125900
TI - Simple cyst of urinary bladder.
AB - Simple cysts are rare in the urinary bladder and can pose a diagnostic dilemma to
both the urologist and the histopathologist. No case study was found in the
database of Elsevier Science Direct, Spring-Link, or PubMed. We present two cases
of subserous cyst in the bladder and discuss the diagnosis and treatment of the
condition. The cystic lesion at bladder dome was detected by radiologic
examination and confirmed by cystoscopy. In case 1, transurethral resection was
first performed which was followed by partial cystectomy; In case 2, the cyst was
removed with the urachus using laparoscopic surgery. The patients recovered
uneventfully and the histopathology showed cysts in subserous layer of urinary
bladder. The bladder cyst should be distinguished from urachal tumor, and
laparoscopic partial cystectomy is the preferred operative procedure.
PMID- 25125901
TI - Urinary bladder radiotherapy-related chondroblastic osteosarcoma: Rare case
report and review of literature.
AB - Radiation-related osteosarcomas are well described malignant mesenchymal
neoplasms, yet their pathogenesis is not fully understood. They are generally
classified into either skeletal osteosarcomas, or their and rare soft tissue
counterpart. The occurrence of osteosarcoma in the urinary bladder (UB) following
radiotherapy is exceedingly rare. To the best of our knowledge, only two cases of
radiation-related urinary bladder osteosarcoma have been published; we herein
describe another case of an 85-year-old man who developed post radiotherapy
chondroblastic osteosarcoma of the urinary bladder four years following initial
surgical resection and radiotherapy for bladder urothelial carcinoma. We believe
that this is the first case of radiation-related chondroblastic osteosarcoma
arising in the urinary bladder. In addition, we review the literature and explore
the possible histogenesis of this rare neoplasm.
PMID- 25125902
TI - Radiation induced sarcoma: Everything comes with a price.
PMID- 25125904
TI - Renal cell carcinoma and plasma cell myeloma: Coincidence or true association?
PMID- 25125903
TI - Renal cell carcinoma and plasma cell myeloma: Unique association and clinical
implications.
AB - Several case series, in the recent past, have postulated an association between
plasma cell myeloma (MM) and renal cell carcinoma (RCC). Population-based data
have revealed a bi-directional association between these two malignancies, which
points to shared risk factors, similar cytokine (Interleukin-6, IL-6)
requirements for growth and survival, and overlapping clinical presentation. The
presence of lytic lesions in a patient with prior RCC may simulate bone
metastasis; thus, leading to a diagnostic pitfall with potentially adverse
clinical implications. Besides these, therapeutic strategies employed for MM have
been tried for RCCs with partial success. We aimed to describe two patients, aged
64 and 54 years, with RCC-MM association, with review of relevant literature; and
create awareness among pathologists/hematologists, and oncologists. Elucidating a
common genetic basis might throw some light in understanding the pathobiology of
these tumors and development of newer targeted therapies.
PMID- 25125905
TI - Dermatofibrosarcoma protuberans of penis: Case report and literature review.
AB - Dermatofibrosarcoma protuberans (DFSP) is a rare mesenchymal skin tumor with
intermediate to low grade malignancy and occasional distant metastasis and high
rate of recurrence locally. It mostly involves trunk, extremities, scalp, and
neck. This article describes a middle-aged married male with a DFSP lesion
involving ventral aspect of glans and distal shaft of penis who underwent local
excision and primary closure. The patient was tumor-free at three years of follow
up.
PMID- 25125906
TI - Rectourethral fistula: A rare complication of injection sclerotherapy.
AB - In the modern era, the incidence of rectourethral fistula (RUF) has been on a
rise due to an increasing number of surgeries being performed for prostatic
carcinoma. Other causes of this condition still remain rare and their management
differs from that of post prostatectomy RUF. We report a rare case of a young man
who presented with leakage of urine per rectum 4 weeks after injection
sclerotherapy for haemorrhoids. A Micturating Cystourethrogram/Retrograde
Cystourethrogram revealed the presence of RUF arising at the level of prostrato
membranous urethra and the urine examination did not show any fecal contamination
of urine. A fistula at the level or verumontanum along with stricture of the
distal penile urethra was demonstrated on urethroscopy. The patient was
successfully managed by dilatation of the stricture segment and urethral
catheterization. RUF can rarely result from injection sclerotherapy and must be
thoroughly evaluated. Cases which present early and have minimal contamination of
urine by fecal contents can be conservatively managed with a simple Foleys
catheterization for 4-6 weeks after ruling out any obstruction distal to the
fistulous tract.
PMID- 25125907
TI - Recurrent dermatomyositis manifesting as a sign of recurrent transitional cell
carcinoma of urinary bladder: Long-term survival.
AB - The association between urological malignancies and paraneoplastic syndromes has
been well documented. We report a case of recurrent dermatomyositis manifesting
as a sign of metastatic recurrence of non-muscle-invasive transitional cell
carcinoma of the bladder, a relationship which has only been referred to in a few
reports. The case highlights a few important clinical challenges; firstly, the
importance of thorough investigation for underlying malignancy in patients with
dermatomyositis, as successful treatment of such malignancy can lead to
resolution of paraneoplastic symptoms, and secondly, a high index of suspicion of
recurrence in cases where paraneoplastic manifestations recur. Metastatic
pulmonary recurrence without local evidence of disease at a follow-up of 4 years
makes this case unique. Moreover, in the light of our experience and reported
literature, a framework is suggested to approach such a diagnostic dilemma in the
future. Description of the case will guide clinicians in the future, in case they
encounter such an unusual clinical scenario. This could also serve as a
hypothesis-generating source for designing future research as well.
PMID- 25125908
TI - Renal allograft transplant recipient with ruptured hydatid native kidney.
AB - Echinococcosis of the kidneys in a renal transplant recipient is extremely rare
and its occurrence being related to immunosuppression is a possibility which
needs further characterisation. Ruptured renal hydatid in a renal transplant
recipient is not reported so far to our best knowledge. We present a 42-year-old
renal allograft receipient who presented one year after transplant with left
flank pain, palpable left lumbar mass and gross hydatiduria. Investigations
revealed a ruptured native hydatid kidney. Patient was managed with a combination
of chemotherapy and left native nephrectomy and discharged in a satisfactory
condition.
PMID- 25125910
TI - Hemorrhagic cystitis: A rare manifestation of organophosphate poisoning.
PMID- 25125909
TI - Atypical isolated urethral tuberculosis associated with inflammatory stenosis and
fistulas.
PMID- 25125911
TI - Estimation of age from development and eruption of teeth.
AB - The developing dentition is used to assess maturity and estimate the age in many
disciplines including anthropology, archeology, forensic science, pediatric
dentistry and orthodontics. There is evidence that dental development is less
effected than skeletal development by malnutrition and hormonal disorders. There
are two methods of dental age assessment, radiographically and by clinically
visualization of eruption of teeth. The clinical method to assess dental age is
based on the emergence of teeth in the mouth. This method is more suitable since
it does not require any special equipment, expertise and is more economical.
Tooth formation is the best choice for estimating the age as variations are less
as compared to other development factors. Eruption of teeth is one of the changes
observed easily among the various dynamic changes that occur from the formation
of teeth to the final shedding of teeth. The times of eruption of teeth are
fairly constant and this can be made use of in ascertaining the average age of
eruption of the tooth. Assessment of age of an individual by examination of teeth
is one of the accepted methods of age determination.
PMID- 25125912
TI - Pulp tissue in sex determination: A fluorescent microscopic study.
AB - AIMS: To determine and compare the reliability of pulp tissue in determination of
sex and to analyze whether caries have any effect on fluorescent body test.
MATERIALS AND METHODS: This study was carried on 50 maxillary and mandibular
teeth (25 male teeth and 25 female teeth), which were indicated for extraction.
The teeth are categorized into 5 groups, 10 each (5 from males and 5 from
females) on the basis of caries progression. The pulp cells are stained with
quinacrine hydrochloride and observed with fluorescent microscope for fluorescent
body. Gender is determined by identification of Y chromosome fluorescence in
dental pulp. RESULTS: Fluorescent bodies were found to be more in sound teeth in
males as the caries increase the mean percentage of fluorescent bodies observed
decreases in males. We also observed the fluorescent spots in females, and the
value of the spot increases in female as the caries progresses, thereby giving
false positive results in females. CONCLUSION: Sex determination by fluorescent
staining of the Y chromosome is a reliable technique in teeth with healthy pulps
or caries with enamel or up to half way of dentin. Teeth with caries involving
pulp cannot be used for sex determination.
PMID- 25125913
TI - Quantitative and qualitative assessment of DNA extracted from saliva for its use
in forensic identification.
AB - Saliva has long been known for its diagnostic value in several diseases. It also
has a potential to be used in forensic science. OBJECTIVE: The objective of this
study is to compare the quantity and quality of DNA samples extracted from saliva
with those extracted from blood in order to assess the feasibility of extracting
sufficient DNA from saliva for its possible use in forensic identification.
MATERIALS AND METHODS: Blood and saliva samples were collected from 20 volunteers
and DNA extraction was performed through Phenol Chloroform technique. The
quantity and quality of isolated DNA was analyzed by spectrophotometery and the
samples were then used to amplify short tandem repeat (STR) F13 using the
polymerase chain reaction. RESULTS: Mean quantity of DNA obtained in saliva was
48.4 +/- 8.2 MUg/ml and in blood was 142.5 +/- 45.9 MUg/ml. Purity of DNA
obtained as assessed by the ratio of optical density 260/280, was found to be
optimal in 45% salivary samples while remaining showed minor contamination.
Despite this positive F13 STR amplification was achieved in 75% of salivary DNA
samples. CONCLUSION: Results of this study showed that saliva may prove to be a
useful source of DNA for forensic purpose.
PMID- 25125914
TI - Comparison of hard tissue interrelationships at the cervical region of teeth
based on tooth type and gender difference.
AB - CONTEXT: Cementoenamel junction (CEJ) represents the anatomic limit between the
crown and root surface. With advancing age and continuous eruption, this area
becomes exposed in the oral media. Consequently, CEJ will be subjected to the
action of various physical and chemical factors that might alter its morphology,
with the cementum being affected in most cases. AIM: To identify the frequency of
hard tissue interrelationships present at the CEJ in relation to different
genders, positions and aspects of tooth using a light microscope. MATERIALS AND
METHODS: The cervical regions of 80 permanent teeth (40 male and 40 female),
extracted for orthodontic or periodontal reasons, were analyzed after
longitudinal ground sections were made in the mesio-distal plane. The CEJ of the
prepared sections was then studied and their frequencies were categorized as:
cementum overlapping enamel, enamel overlapping cementum, edge-to-edge
relationship and the presence of gap junctions. STATISTICAL ANALYSIS: Chi-square
test performed using SPSS 15 software. RESULTS: Edge-to-edge contact of the
cementum and enamel was most frequent, followed by gap junction and cementum
overlapping the enamel, respectively. Chi-square test revealed no statistically
significant differences with respect to the gender and tooth aspect, whereas the
result was significant when the position of the tooth was studied. CONCLUSION:
The observations of the study indicate a considerable morphological diversity in
the anatomical pattern of CEJ. It can be concluded that the region should be
protected against dentinal sensitivity, erosion, abrasion, abfraction and
resorption, as it is more prone to cervical pathologies.
PMID- 25125915
TI - A comparative study to evaluate the vertical position of maxillary central
incisor and canine in relation to incisive papilla line.
AB - OBJECTIVES: The aim of the study was to determine the vertical distance of
maxillary central incisor (CI) and maxillary canine (CA) from the incisive
papilla (IP) line and their variation with age and sex. MATERIALS AND METHODS: A
total of 120 dentulous subjects following the inclusion and exclusion criteria
were randomly selected from the local population. On the basis of gender and age,
subjects were divided into four groups: Ma, Mb, Fa and Fb . Maxillary impressions
of selected subjects were made and corresponding casts were retrieved. The cast
was positioned on the surveyor and the center of IP was transferred to the labial
side of maxillary right CI and CA regions with the help of analyzing rod of the
surveyor and a line was drawn in this region which was referred to as "IP line".
The measurements were made from the IP line to the mesio-incisal line angle of
right maxillary CI-IP and cusp tip of right maxillary CA with the help of digital
vernier caliper (CA to IP). RESULT: The mean vertical distance of maxillary CI-IP
ranged from 6.31 +/- 0.74 mm to 7.04 +/- 0.87 mm and the mean vertical distance
of maxillary CA-IP ranged from 5.83 +/- 0.80 mm to 6.30 +/- 0.82 mm. CONCLUSION:
The CA position in relation to the IP line is more stable to its position than
the CI position irrespective of age and sex.
PMID- 25125916
TI - A call for a new speciality: Forensic odontology as a subject.
AB - BACKGROUND: Forensic science is defined as a discipline concerned with the
application of science and technology to the detection and investigation of crime
and administration of justice, requiring the coordinated efforts of a
multidisciplinary team. Dental identification remains one of the most reliable
and frequently applied methods of identification. Hence, it can be defined as the
science that deals with evidence from the dental and oral structures and is a
specialty in itself. OBJECTIVES: To analyze the level of awareness of Forensic
Odontology amongst the individuals from the field of dentistry with the help of a
survey. MATERIALS AND METHODS: A questionnaire was prepared and a survey was
conducted with a sample size of 200 divided in four groups. RESULTS: Revealed
inadequate knowledge, poor attitude, and lack of practice of forensic odontology
prevailing among the dentists. CONCLUSION: Our study reflects the current
situation of our country in the field of forensic odontology, which could be
improved by introducing forensic odontology as a subject in the dental curriculum
at both the undergraduate and the post-graduate levels.
PMID- 25125917
TI - Stature and gender determination and their correlation using odontometry and
skull anthropometry.
AB - BACKGROUND: When the body has been mutilated, it is common to have the
extremities or head amputated from the trunk. In concern with forensic
odontology, an estimate must have been made based on the correlation of
osteometry along with odontometry in determining sex, race and stature.
OBJECTIVE: The objective of this study is to investigate and correlate height and
gender from odontometry and anthropometric data of the skull. MATERIALS AND
METHODS: The study was conducted in the Department of Oral and Maxillofacial
Pathology and Microbiology, I.T.S Center for Dental studies and Research,
Muradnagar, Ghaziabad (UP) with the representative study subjects of 60 patients
as 30 males and 30 females in the age group of 15-25 years. The selected
parameters were measured and then correlated to investigate stature and gender
from odontometry and anthropometric data of the skull. RESULTS: On linear
regression analysis, the selected parameters were found to be statistically
significant predictor of height. It was also established by Karl Pearson's
coefficient correlation that the left mandibular canine index for female was
statistically significant to show sexual dimorphism. CONCLUSION: In the emerging
field of forensic odontology, skull anthropometry, odontometry exhibits stature
determination and strong sexual dimorphism.
PMID- 25125918
TI - Gender determination from pulpal tissue.
AB - OBJECTIVE: To evaluate the diagnostic performance of X (Barr body [BB]) and Y (F
body [FB]) chromosomes observed in dental pulp tissue for gender determination of
an individual. MATERIALS AND METHODS: The study was carried out on 100 teeth (50
male and 50 female), which were indicated for extraction. The teeth were
sectioned at various intervals (within 12 h to 49 days post-extraction), and the
pulpal tissue was obtained. Two slides for each pulp tissue were prepared, one
for 5% Quinacrine dihydrochloride stain (FB) and the other for Hemotoxylin and
Eosin stain (BB). The slides were then observed under the fluorescent microscope
for FB and under the light microscope for the BB respectively. RESULTS: Gender
determination from human pulp is possible up to 7 weeks. The percentage of FB and
BB decrease gradually as the time interval increases. Further, an equation was
derived from the data based on the canonical discriminant function coefficients.
CONCLUSION: The determination of gender based on a joint search for the presence
or absence of X (BB) and Y (FB) Chromosome is a reliable and cost-effective
technique.
PMID- 25125919
TI - Age estimation from physiological changes of teeth: A reliable age marker?
AB - BACKGROUND: Age is an essential factor in establishing the identity of a person.
Teeth are one of the most durable and resilient part of skeleton. Gustafson
(1950) suggested the use of six retrogressive dental changes that are seen with
increasing age. AIM: The aim of the study was to evaluate the results and to
check the reliability of modified Gustafson's method for determining the age of
an individual. MATERIALS AND METHODS: Total 70 patients in the age group of 20-65
years, undergoing extraction were included in this present work. The ground
sections of extracted teeth were prepared and examined under the microscope.
Modified Gustafson's criteria were used for the estimation of age. Degree of
attrition, root translucency, secondary dentin deposition, cementum apposition,
and root resorption were measured. A linear regression formula was obtained using
different statistical equations in a sample of 70 patients. RESULTS: The mean age
difference of total 70 cases studied was +/-2.64 years. Difference of actual and
calculated age was significant and was observed at 5% level of significance, that
is, t-cal > t-tab (t-cal = 7.72). P < 0.05, indicates that the results were
statistically significant. CONCLUSION: The present study concludes that
Gustafson's method is a reliable method for age estimation with some proposed
modifications.
PMID- 25125920
TI - Rugae pattern in a sample of population of Meerut - An institutional study.
AB - CONTEXT: Many studies on rugae pattern have been done on various samples of
population, but no study has so far been done to assess the rugae pattern of
population of western Uttar radesh, especially Meerut. AIMS: This study was aimed
to assess the rugae pattern in males and females of a sample of population of
Meerut, which may be an additional method of determining gender when dealing with
any crime or with mutilated bodies that have undergone damage beyond recognition.
SETTINGS AND DESIGN: A total of 100 Class I dentulous subjects, 50 male and 50
female patients reporting to the outpatient department of Kalka Dental College,
Meerut, Uttar Pradesh were randomly selected with an age range between 20-30
years. Exclusion criteria were subjects >14 years of age, congenital
malformations, previous orthognathic surgery, allergy to impression material,
bony and soft tissue protuberances, active lesions, deformity or scars and trauma
of the palate. Prior approval from the Institutional Ethical Committee was taken.
SUBJECTS AND METHODS: Alginate impressions of palate of selected patients were
poured in dental stone and rugae pattern was identified and analyzed by a single
rater employing Thomas and Kotze's (1983) method. STATISTICAL ANALYSIS USED: Two
sample t-test and Chi-Square tests were used for comparison of means and
relationship between the attributes. A significance level of 5% was considered as
critical value. RESULTS: No significant difference was noted in total number or
length of rugae between the genders. However, statistically significant
difference in the circular type in males and converge type in females was
observed. CONCLUSION: Rugae pattern can be used as a method of differentiation
between males and females to corroborate the findings of other methods such as
anthropometric evaluation of the cranium and dental characteristics.
PMID- 25125921
TI - Experimental model of developing and analysis of lip prints in atypical surface:
A metallic straw (bombilla).
AB - BACKGROUND: The interaction between the offender and the victim produces visible
or latent prints on objects and utensils. The study of lip prints has reportedly
stayed away from the basic cinematic concept of the lip-to-surface relationship.
MATERIALS AND METHODS: Three regular powders were used to reveal the latent lip
prints on a typical metallic straw called bombilla, and the revealed prints were
photographed, preserved, and analyzed. RESULTS: Better definition was observed in
the lower lip print, and nine anatomical patterns were identified, but a higher
definition of wrinkles was observed with indestructible white powder. CONCLUSION:
Knowledge of labial dynamics, the real value of the processed surfaces, and the
need for testing in field conditions are discussed.
PMID- 25125922
TI - Molecular sex identification of dry human teeth specimens from Sokoto,
Northwestern Nigeria.
AB - BACKGROUND: The advent of molecular techniques has revolutionized the ability of
scientists to estimate the sex of individuals. Forensic odontology plays an
important role in establishing the sex of victims with bodies mutilated beyond
recognition due to major disaster. The genetic difference between males and
females is defined by the presence or absence of the Y-chromosome. The use of
alphoid-repeat primers in sex estimation was first applied on dried blood.
Generally, the X, Y alphoid repeats blind test attest to the accuracy of genetic
testing, and also point the potential for occasional error in morphometric
sexing. AIM: To estimate genetic sex of dry human teeth specimens from Sokoto,
Northwestern Nigeria, using polymerase chain reaction (PCR). MATERIALS AND
METHODS: A single-blind study of DNA analysis for sex estimation of nine dry
human teeth specimens from Sokoto, Northwestern Nigeria, through PCR, using
alphoid repeats primers, was undertaken. RESULTS: The genetic sex of each group
of the teeth samples were accurately (100%) identified. For each group of teeth,
PCR Sensitivity = 100%, Specificity = 0%, Predictive value of positive test =
100%, Predictive value of negative test = 0%, False positive rate = 0%, False
negative rate = 0%, Efficiency of test = 100%. Fisher's exact probability test P
= 1. Z-test: z- and P values were invalid. CONCLUSION: This study has
demonstrated the successful use of alphoid-repeat primers in genetic sex
identification of human dry teeth samples from Sokoto, Northwestern Nigeria. This
is the first known study estimating the sex of human dry teeth specimens by means
of PCR in Nigeria. There is need for further studies in Nigeria to complement the
findings of this study.
PMID- 25125924
TI - Role of dental implants in forensic identification.
PMID- 25125923
TI - Volume analysis of heat-induced cracks in human molars: A preliminary study.
AB - CONTEXT: Only a few methods have been published dealing with the visualization of
heat-induced cracks inside bones and teeth. AIMS: As a novel approach this study
used nondestructive X-ray microtomography (micro-CT) for volume analysis of heat
induced cracks to observe the reaction of human molars to various levels of
thermal stress. MATERIALS AND METHODS: Eighteen clinically extracted third molars
were rehydrated and burned under controlled temperatures (400, 650, and 800
degrees C) using an electric furnace adjusted with a 25 degrees C increase/min.
The subsequent high-resolution scans (voxel-size 17.7 MUm) were made with a
compact micro-CT scanner (SkyScan 1174). In total, 14 scans were automatically
segmented with Definiens XD Developer 1.2 and three-dimensional (3D) models were
computed with Visage Imaging Amira 5.2.2. The results of the automated
segmentation were analyzed with an analysis of variance (ANOVA) and uncorrected
post hoc least significant difference (LSD) tests using Statistical Package for
Social Sciences (SPSS) 17. A probability level of P < 0.05 was used as an index
of statistical significance. RESULTS: A temperature-dependent increase of heat
induced cracks was observed between the three temperature groups (P < 0.05, ANOVA
post hoc LSD). In addition, the distributions and shape of the heat-induced
changes could be classified using the computed 3D models. CONCLUSION: The
macroscopic heat-induced changes observed in this preliminary study correspond
with previous observations of unrestored human teeth, yet the current
observations also take into account the entire microscopic 3D expansions of heat
induced cracks within the dental hard tissues. Using the same experimental
conditions proposed in the literature, this study confirms previous results, adds
new observations, and offers new perspectives in the investigation of forensic
evidence.
PMID- 25125928
TI - Effect of Silver Coating on Barium Titanium Oxide Nanoparticle Toxicity.
AB - Nanoparticles are presently being studied for optical and biomedical applications
such as medical imaging and drug delivery. Nanoparticles impact the cellular
environment due to many variables such as size, shape, and composition. How these
factors affect cell viability is not fully understood. The purpose of this study
is to test the toxicity effects of silver coating (Ag@) Barium Titanium Oxide
(BaTiO3) nanoparticles on Rhesus Monkey Retinal Endothelial cells (RhREC's) in
culture. The addition of silver to the nanoparticles increases their nonlinear
optical properties significantly, making the Ag@BaTiO3 nanoparticles good
candidates for nonlinear microscopy contrast agents. We hypothesize that by
silver coating nanoparticles, there will be an increase in cell viability at
higher concentrations when compared to non-silver coated nanoparticles. RhREC's
were treated with BaTiO3 and Ag@BaTiO3 at concentrations of 0, 1.0, 10.0, and
100ug/ml for 24 hours at 37 degrees C + 5%CO2. After 24 hour incubation with
respective nanoparticles, cell viability was determined using the trypan blue dye
exclusion method. Treatment with 0, 1.0 and 10.0ug/ml of Ag@BaTiO3 had minimal
effect on cell viability, with 90% viable cells remaining at the end of the 24
hours treatment period. However, cells treated with 100ug/ml of Ag@BaTiO3
resulted in a decrease to 51% viable cells. Comparatively, cells treated with 0,
1.0 and 10ug/ml of BaTiO3 had no significant effect on cell viability (90% viable
cells after treatment) while the 100ug/ml treatment resulted in a decrease to 29%
viable cells. These results show that silver coating of BaTiO3 nanoparticles has
a protective effect on cellular toxicity at high concentrations.
PMID- 25125929
TI - SUPPORT FOR THE CONTINUATION OF FEMALE GENITAL MUTILATION AMONG ADOLESCENTS IN
JIMMA ZONE, SOUTHWEST ETHIOPIA.
AB - BACKGROUND: Female genital mutilation/cutting is a harmful practice which has
effect on female's wellbeing. However, the practice has continued to prevail in
many cultures. Research on the social determinants of the practice and its
continuation are scarce. The objective of this study was to assess whether
attitude towards the continuation of female genital mutilation is predicted by
gender role perception among adolescents in Jimma zone. METHODS: This study used
data collected in the first round of Jimma Longitudinal Family Survey of Youth. A
total of 2084 adolescents were identified from 3700 households and one adolescent
were interviewed from each household using structured questionnaire. Data on the
socio-demographic characteristics, religiosity, access to electronic media,
perception of gender role, attitude towards continuation of Female circumcision
was collected. Descriptive and multivariate statistical techniques were used to
analyze the data using SPSS for windows version 16.0. Statically tests were
performed at the level of significance of 5%. RESULTS: Of the 2084 adolescents,
1146 (55.0%) were aged 12-14 years, 1025 (49.2%) females and 749 (35.9%) from
rural areas. The majority, 1289 (61.9%) were Muslims and 1351 (64.8%) Oromo. Five
hundred seventy three (28.1%) of the male youth did not agree to the importance
of marrying a circumcised girl. However, 149 (13.8%) and 258 (12.7%) agreed that
it is very important and important, to marry a circumcised girl, respectively. On
multivariate logistic regression analysis, perception of gender role, sex, place
of residence, highest education in the household and religion remained to be
important predictors of attitude towards the continuation of female genital
mutilation after adjustment for age and ethnicity. Adolescents who had low gender
role perception were 1.4 times more likely to have a positive attitude towards
the continuation of the female genital mutilation (OR: 95%CI, 1.41: 1.02-1.94).
Female adolescents were 36% less likely to support (P<0.01) the continuation of
FGM compared to their male counter parts (OR: 0.64; 95%CI: 0.49, 0.83). Compared
to urban youth, those who live in semi urban and rural areas were 1.46 and 1.52
times more likely to have a positive attitude towards the continuation of the FGM
practice, respectively (P<0.05). Similarly the Probability of having positive
attitude towards the continuation of the FGM practice decreased steadily as the
highest educational level in the household increased. CONCLUSION: One-fifth of
the youth support the continuation of the practice. Low gender roles perception,
being from the rural areas, household's lower level of education and being Muslim
were strong predictors of the attitude towards the continuation of female genital
mutilation. Improving perception of adolescents towards gender roles through
effective behavior change communication, and involving religious leaders in the
campaign against the practice of female genital mutilation is recommended as a
useful strategy to ban the practice.
PMID- 25125930
TI - Substance Use as a Risk Factor for Intimate Partner Violence Overlap:
Generational Differences Among Hispanic Young Adults.
AB - Intimate partner violence (IPV) research often focuses on either the victims of
IPV or the perpetrators of IPV. Recent studies have documented the existence of a
group of victim-perpetrators, for example, they perpetrate IPV and are also the
victims of IPV. The current study examines this overlap in IPV perpetration and
victimization among a nationally representative, longitudinal sample of 1,488
Hispanics with a focus on generational status. Results from group-based
trajectory models and survey multinomial regression techniques suggest that
alcohol and marijuana use over time are salient risk factors for IPV
perpetration, IPV victimization, and IPV overlap. Study limitations and
implications are discussed.
PMID- 25125931
TI - Moral Violations Reduce Oral Consumption.
AB - Consumers frequently encounter moral violations in everyday life. They watch
movies and television shows about crime and deception, hear news reports of
corporate fraud and tax evasion, and hear gossip about cheaters and thieves. How
does exposure to moral violations influence consumption? Because moral violations
arouse disgust and because disgust is an evolutionarily important signal of
contamination that should provoke a multi-modal response, we hypothesize that
moral violations affect a key behavioral response to disgust: reduced oral
consumption. In three experiments, compared with those in control conditions,
people drank less water and chocolate milk while (a) watching a film portraying
the moral violations of incest, (b) writing about moral violations of cheating or
theft, and (c) listening to a report about fraud and manipulation. These findings
imply that "moral disgust" influences consumption in ways similar to core
disgust, and thus provide evidence for the associations between moral violations,
emotions, and consumer behavior.
PMID- 25125932
TI - The influence of spinal manipulation on the practitioner-something to consider in
our instruction of manual therapy?
PMID- 25125934
TI - The relationship between various anatomical landmarks used for localizing the
first rib during surface palpation.
AB - OBJECTIVES: To assess the relationship between anatomical landmarks used to
locate the first rib during surface palpation. One currently cited technique
suggests locating the width of the transverse processes (TPs) of the first
cervical vertebrae (C1) to determine the estimated width of the first thoracic
vertebrae (T1) TP, allowing for subsequent palpation of the first rib laterally
to the transverse process of T1. Based on anatomical structural relationships,
the authors propose an additional method of locating the first rib, lateral to T1
TP, by palpating through the trapezius muscle at the width of the mastoid process
(MP). METHODS: Overlying tissue of the bilateral MP, C1 TPs, and T1 TPs of 28
cadavers were removed. Measurements of the left to right spans at the following
structures were collected using a digital caliper: mastoid process, C1 TP, and T1
TP. Measurements were used to determine the agreement between each anatomical
structural span. RESULTS: The mean absolute difference (standard deviation, SD)
between C1 TP span versus T1 TP span was 3.9 (+/-2.58) mm with an intraclass
correlation coefficient (ICC) of 0.88 (95% CI = 2.9-4.9). The mean absolute
difference between MP span and T1 TP span was 35.4 (+/-6.46) mm with an ICC of
0.71 (95% CI = 33.0-37.8). DISCUSSION: This study confirms the anatomical
accuracy and feasibility of using the C1 TP span to determine the general width
of the T1 TP span while palpating for the first rib just lateral to the T1 TP.
Additionally, this study demonstrates that the more easily palpated mastoid
process serves as an effective landmark to identify a width sufficiently lateral
to the T1 TP, appropriate for first rib palpation through the trapezius muscle.
PMID- 25125933
TI - The effectiveness of strain counterstrain in the treatment of patients with
chronic ankle instability: A randomized clinical trial.
AB - STUDY DESIGN: Randomized clinical trial. OBJECTIVE: To determine the effect of
strain counterstrain (SCS) on dynamic balance and subjective sense of instability
in individuals with chronic ankle instability (CAI). Although many studies have
been published on CAI, the cause for this common clinical dysfunction remains
inconclusive. No studies have assessed the effectiveness of SCS on CAI. METHODS:
At baseline all participants completed a demographic questionnaire, the star
excursion balance test (SEBT), and the foot and ankle ability measure (FAAM).
Following the baseline evaluation, participants were randomized into the SCS
experimental group (EG) (n = 13) or the sham SCS group (SG) (n = 14). All
participants received the assigned treatment once a week for 4 weeks and
participated in a prescribed exercise program. At week 4, all participants
repeated the outcome measures and completed a global rating of change (GROC)
form. The primary aim was examined with a two-way analysis of variance (ANOVA).
RESULTS: A significant group-by-time interaction was found for seven directions
in the SEBT (P<0.031). For subjective measures, no significant group-by-time
interaction was found for the FAAM (P>0.548), but the GROC revealed a significant
difference (P = 0.014) in the mean score for the EG (3.92+/-1.66) when compared
to the SG (2.43+/-1.66). DISCUSSION: Although SCS may not have an effect on
subjective ankle function in individuals with CAI, preliminary evidence suggests
that SCS may lead to an improvement in dynamic ankle stability and the subjective
sense of ankle instability. LEVEL OF EVIDENCE: Therapy, Level 1b.
PMID- 25125935
TI - Adverse events following trigger point dry needling: a prospective survey of
chartered physiotherapists.
AB - OBJECTIVES: Trigger point dry needling (TrP-DN) is commonly used to treat persons
with myofascial pain, but no studies currently exist investigating its safety.
The aim of this study was to determine the incidence of Adverse Events (AEs)
associated with the use of TrP-DN by a sample of physiotherapists in Ireland.
METHODS: A prospective survey was undertaken consisting of two forms recording
mild and significant AEs. Physiotherapists who had completed TrP-DN training with
the David G Simons Academy (DGSA) were eligible to take part in the study. Data
were collected over a ten-month period. RESULTS: In the study, 39
physiotherapists participated and 1463 (19.18%) mild AEs were reported in 7629
treatments with TrP-DN. No significant AEs were reported giving an estimated
upper risk rate for significant AEs of less than or equal to (<=) 0.04%. Common
AEs included bruising (7.55%), bleeding (4.65%), pain during treatment (3.01%),
and pain after treatment (2.19%). Uncommon AEs were aggravation of symptoms
(0.88%), drowsiness (0.26%), headache (0.14%), and nausea (0.13%). Rare AEs were
fatigue (0.04%), altered emotions (0.04%), shaking, itching, claustrophobia, and
numbness, all 0.01%. DISCUSSION: While mild AEs were very commonly reported in
this study of TrP-DN, no significant AEs occurred. For the physiotherapists
surveyed, TrP-DN appeared to be a safe treatment.
PMID- 25125936
TI - Thoracic manipulation versus mobilization in patients with mechanical neck pain:
a systematic review.
AB - OBJECTIVES: Thoracic manipulation is widely used in physical therapy and has been
shown to be effective at addressing mechanical neck pain. However, thoracic
mobilization may produce similar effects. The purpose of this systematic review
was to evaluate the current literature regarding the effectiveness of thoracic
manipulation versus mobilization in patients with mechanical neck pain. METHODS:
ProQuest, NCBI-PubMed, APTA's Hooked on Evidence, Cochrane Library, CINAHL and
SPORTDiscus were searched to identify relevant studies. Fourteen studies meeting
the inclusion criteria were analyzed using the Physiotherapy Evidence Database
(PEDro) scale and the GRADE approach. RESULTS: The literature as assessed by the
PEDro scale was fair and the GRADE method showed overall quality ranging from
very low to moderate quality. The 14 included studies showed positive outcomes on
cervical pain levels, range of motion, and/or disability with the use of thoracic
manipulation or mobilization. There was a paucity of literature directly
comparing thoracic manipulation and mobilization. DISCUSSION: Current limitations
in the body of research, specifically regarding the use of thoracic mobilization,
limit the recommendation of its use compared to thoracic manipulation for
patients with mechanical neck pain. There is, however, a significant amount of
evidence, although of varied quality, for the short-term benefits of thoracic
manipulation in treating patients with this condition. Further high quality
research is necessary to determine which technique is more effective in treating
patients with mechanical neck pain.
PMID- 25125937
TI - Accuracy of physical therapists' prognosis of low back pain from the clinical
examination: a prospective cohort study.
AB - OBJECTIVES: To investigate, in patients with chronic or recurrent low back pain
(LBP), the predictive validity of history items, demographic variables, outcome
measure questionnaire scores, clinical examination items, and physical
therapists' (PTs') summative estimation of prognosis on a four-point scale.
Little is known about the ability of PTs to predict functional outcomes for
patients with LBP. METHODS: This was a multi-centre prospective cohort study of
138 patients with LBP. We used backward stepwise linear regression modelling to
estimate the predictive validity of the baseline variables. The endpoint outcome
measure was the 18-item Roland-Morris Disability Questionnaire (RM18) at 1 year.
RESULTS: Of 138 patients with LBP recruited, 89 (64%) completed follow-up at one
year. Univariate analysis indicated that PTs' opinion of prognosis (P = 0.01) and
eleven other baseline variables were significantly associated with RM18 at 12
months. In the final multivariate model PTs' opinion of prognosis (P = 0.022;
beta = 0.73, CI 0.55, 0.95), an abnormality detected by passive physiological
flexion testing (P = 0.043, beta = 1.61, CI 1.02, 2.57), heavy work (P = 0.069,
beta = 0.80, CI 0.62, 1.01), and age (P = 0.079, beta = 1.01 CI 0.99, 1.04) were
independent prognostic factors for RM18 outcome, explaining 24% of the variance
in the model. CONCLUSIONS: Musculoskeletal PTs' summative clinical impression
regarding prognosis, following a clinical examination, provides a valid
predictive estimation of functional outcome at 1 year in patients with chronic or
recurrent LBP.
PMID- 25125938
TI - Metastatic cancer mimicking mechanical low back pain: a case report.
AB - OBJECTIVE AND IMPORTANCE: The purpose of this report is to describe the clinical
course of a patient referred to physiotherapy (PT) for the treatment of low back
pain who was subsequently diagnosed with metastatic non-small cell carcinoma of
the lung. CLINICAL PRESENTATION: A 48-year old woman was referred to PT for the
evaluation and treatment of an insidious onset of low back pain of 2 month
duration. The patient did not have a history of cancer, recent weight changes, or
general health concerns. The patient's history and physical examination were
consistent with a mechanical neuromusculoskeletal dysfunction and no red flag
findings were present that warranted immediate medical referral. INTERVENTION:
Short-term symptomatic improvements were achieved using the treatment-based
classification approach. However, despite five PT sessions over the course of 5
weeks, the patient did not experience long-term symptomatic improvement. On the
sixth session, the patient reported a 2-day history of left hand weakness and
headaches. This prompted the physiotherapist to refer the patient to the
emergency department where she was diagnosed with lung cancer. CONCLUSION:
Differential diagnosis is a key component of PT practice. The ability to
reproduce symptoms or achieve short-term symptomatic gains is not sufficient to
rule out sinister pathology. This case demonstrates how extra caution should be
taken in patients who are smokers with thoracolumbar region pain of unknown
origin. The need for caution is magnified when one can achieve no more than short
term improvements in the patient's symptoms.
PMID- 25125939
TI - Clinical Correlates of Autosomal Chromosomal Abnormalities in an Electronic
Medical Record-Linked Genome-Wide Association Study: A Case Series.
AB - Although mosaic autosomal chromosomal abnormalities are being increasingly
detected as part of high-density genotyping studies, the clinical correlates are
unclear. From an electronic medical record (EMR)-based genome-wide association
study (GWAS) of peripheral arterial disease, log-R-ratio and B-allele-frequency
data were used to identify mosaic autosomal chromosomal abnormalities including
copy number variation and loss of heterozygosity. The EMRs of patients with
chromosomal abnormalities and those without chromosomal abnormalities were
reviewed to compare clinical characteristics. Among 3336 study participants,
0.75% (n = 25, mean age = 74.8 +/- 10.7 years, 64% men) had abnormal intensity
plots indicative of autosomal chromosomal abnormalities. A hematologic malignancy
was present in 8 patients (32%), of whom 4 also had a solid organ malignancy
while 2 patients had a solid organ malignancy only. In 50 age- and sex-matched
participants without chromosomal abnormalities, there was a lower rate of
hematologic malignancies (2% vs 32%, P < .001) but not solid organ malignancies
(20% vs 24%, P = .69). We also report the clinical characteristics of each
patient with the observed chromosomal abnormalities. Interestingly, among 5
patients with 20q deletions, 4 had a myeloproliferative disorder while all 3 men
in this group had prostate cancer. In summary, in a GWAS of 3336 adults, 0.75%
had autosomal chromosomal abnormalities and nearly a third of them had
hematologic malignancies. A potential novel association between 20q deletions,
myeloproliferative disorders, and prostate cancer was also noted.
PMID- 25125941
TI - Cu(II) Catalytic Reduction of Cr(VI) by Tartaric Acid Under the Irradiation of
Simulated Solar Light.
AB - Cu(II) catalytic reduction of Cr(VI) by tartaric acid under the irradiation of
simulated solar light was investigated through batch experiments at pHs from 3 to
6 and at temperatures from 15 degrees C to 35 degrees C. Results demonstrated
that introduction of Cu(II) could markedly improve reduction of Cr(VI) in
comparison with tartaric acid alone. Optimal removal of Cr(VI) was achieved at pH
4. Reduction of Cr(VI) increased with increasing temperatures and initial
concentrations of Cu(II) and tartaric acid. The catalytic role of Cu(II) in the
reduction of Cr(VI) was ascribed to the formation of Cu(II)-tartaric acid
complex, which generated active reductive intermediates, including Cu(I) and
tartaric acid radicals through a pathway of metal-ligand-electron transfer with
light. Cu(II) photocatalytic reduction of Cr(VI) by tartaric acid followed pseudo
zero-order kinetics with regard to Cr(VI), and the activation energy was
calculated to be 21.48 kJ/mol. To date, such a role of Cu(II) has not been
reported. The results from the present study are helpful in fully understanding
the photochemical reductive behavior of Cr(VI) in the presence of both tartaric
acid and Cu(II) in soil and aquatic environments.
PMID- 25125940
TI - Social-Cognitive Moderators of the Relationship between Peer Victimization and
Suicidal Ideation among Psychiatrically Hospitalized Adolescents.
AB - Peer victimization among children and adolescents is a major public health
concern, given its widespread individual and societal ramifications. Victims of
peer aggression often face significant levels of psychological distress and
social difficulties, such as depression, suicidal ideation, suicide attempts, and
social rejection. The purpose of the present study was to examine whether
cognitive distortions and perceptions of social support moderate the association
between peer victimization and suicidal thoughts among psychiatrically
hospitalized adolescents. Participants included 183 psychiatrically hospitalized
adolescents (ages 13-18). In multiple regression analyses that controlled for
gender, social and cognitive factors served as significant resources factors.
Cognitive factors also moderated the relationship between peer victimization and
suicidal ideation.
PMID- 25125942
TI - A Multistep Chaotic Model for Municipal Solid Waste Generation Prediction.
AB - In this study, a univariate local chaotic model is proposed to make one-step and
multistep forecasts for daily municipal solid waste (MSW) generation in Seattle,
Washington. For MSW generation prediction with long history data, this
forecasting model was created based on a nonlinear dynamic method called phase
space reconstruction. Compared with other nonlinear predictive models, such as
artificial neural network (ANN) and partial least square-support vector machine
(PLS-SVM), and a commonly used linear seasonal autoregressive integrated moving
average (sARIMA) model, this method has demonstrated better prediction accuracy
from 1-step ahead prediction to 14-step ahead prediction assessed by both mean
absolute percentage error (MAPE) and root mean square error (RMSE). Max error,
MAPE, and RMSE show that chaotic models were more reliable than the other three
models. As chaotic models do not involve random walk, their performance does not
vary while ANN and PLS-SVM make different forecasts in each trial. Moreover, this
chaotic model was less time consuming than ANN and PLS-SVM models.
PMID- 25125943
TI - Greek financial crisis: consequences in the healthcare of diabetes and its
complications.
PMID- 25125944
TI - Functional hyposplenism.
AB - Functional hyposplenism is a condition accompanying many diseases such as sickle
cell disease, celiac disease, alcoholic liver disease, hepatic cirrhosis,
lymphomas and autoimmune disorders. It is characterised mostly by defective
immune responses against infectious agents, especially encapsulated organisms,
since the spleen is thought to play an important role in the production and
maturation of B-memory lymphocytes and other substances like opsonins, both of
which are considered crucial elements of the immune system for fighting
infections. It is also associated with thrombocytosis, which might lead to
thromboembolic events. Functional hyposplenism is diagnosed by the presence of
Howell-Jolly bodies and pitted erythrocytes in the peripheral blood smear, and by
nuclear imaging modalities such as spleen scintigraphy with the use of Technetium
99m and/or spleen scintigraphy with the use of heat-damaged Technetium-99m
labeled erythrocytes. Severe infections accompanying functional hyposplenism can
lead to the overwhelming post infection syndrome, which can often be fatal.
Identifying patients with functional hyposplenism is important because simple
measures such as vaccination against common infective microorganisms (e.g.
Streptococcus pneumonia, Neisseria meningitides and Haemophilous influenzae) and
antibiotic therapy when needed are considered beneficial in diminishing the
frequency and gravity of the infections accompanying the syndrome.
PMID- 25125945
TI - Wall shear stress oscillation and its gradient in the normal left coronary artery
tree bifurcations.
AB - BACKGROUND: It is known that blood flow properties such as low/ oscillatory wall
shear stress (WSS), high blood viscosity, low blood velocity and high
concentration of low density lipoprotein (LDL) macromolecules, are some of the
main flow parameters causing atherosclerosis. Limited research has been
undertaken on the pulsatile WSS and WSS gradient (WSSG) analysis focusing in the
differentiation between the bifurcation itself and the lateral to it walls in a
normal left coronary artery (LCA). The results obtained show the flow
characteristics and qualify the spatial and temporal distribution of WSS ant its
gradient in regions close to the LCA tree flow dividers and in opposite to them
areas. METHODS: A 3D computer generated model of the LCA tree based on averaged
human data extracted from angiographies was developed for computational fluid
dynamics analysis. Physiological phasic flow velocity is incorporated as entrance
boundary condition. RESULTS: The instantaneous min wall shear stress oscillates
from 0.45 to 2.84 N/m(2) at the flow divider and from 0.25 to 1.28 N/m(2) at the
lateral walls of the main bifurcation. However, for the D1-S1 bifurcation (first
diagonal-first septal), the instantaneous min wall shear stress oscillates from
0.6 to 3.85 N/m(2) at the flow divider and from 0.6 to 2.65 N/m(2) at the lateral
walls. Mean wall shear stress, from max systole to max diastole, experiences a
129.0 % increase at the main bifurcation flow divider. The difference between max
and min wall shear stress for the flow divider of the main bifurcation, as it is
compared with the max wall shear stress over the entire cardiac pulse, attains a
maximum value of 81.1 % for the lateral walls and 60.0 % at the peak of diastole.
At the D1-S1 bifurcation, the corresponding difference values are 69.0% and 57.0
% for the lateral walls and flow divider, respectively. The mean wall shear
stress gradient experiences a 123.0 % increase from max systole to max diastole
at the main bifurcation flow divider and 153.0 % at main bifurcation lateral
walls. CONCLUSIONS: Proximal LCA bifurcation exhibit lower spatial wall shear
stress and lower wall shear stress gradient values compared to distal
bifurcations. The lateral walls compared to the bifurcation itself are exposed to
low WSS and WSSG. With regards to the temporal variation, wall shear stress and
its gradient exhibited lower values throughout systole as compared to diastole,
suggesting a possible atherogenic effect of both the systolic phase by itself as
well as the phasic oscillation of wall shear stress and its gradient from systole
to diastole.
PMID- 25125946
TI - N-acetylcycsteine attenuates the deleterious effects of radiation therapy on inci
sional wound healing in rats.
AB - BACKGROUND: During preoperative radiotherapy, effective doses of ionizing
radiation occasionally cause wound complications after subsequent surgery. This
study was designed to determine the effects of intraperitoneally or orally
administered N-acetylcysteine (NAC) on anastomotic healing of irradiated rats.
MATERIAL & METHODS: Forty Wistar albino rats were randomized into four groups
containing 10 rats each. A 3 cm long surgical full-thickness midline laparotomy
was performed to all groups (Groups 1-4). Group 1 was designed as a control group
without radiation therapy and NAC treatment. Groups 2, 3 and 4 received a single
abdominal dose of 10 Gy irradiation before laparotomy and groups 3 and 4 received
oral and intraperitoneal NAC, respectively. RESULTS: Group comparisons
demonstrated that breaking strength was significantly higher in NAC treated rats.
A statistically significant difference was determined in terms of superoxide
dismutase (SOD), malondealdehyde (MDA) and glutation (GSH) values between groups
(p<0.001). Nevertheless, advanced oxidation protein products (AOPP) levels were
found to be similar between groups (p=0.163). Serum GSH and SOD levels were
significantly higher in groups 3 and 4 when compared to group 2 (p < 0.05).
Similarly, there was a significant increase in serum MDA concentration,
predicting lipid peroxidation, in group 2 when compared to groups 1, 3 and 4 (p <
0.05). There was not a significant difference between Groups 3 and 4 regarding
GSH, MDA, SOD, and AOPP levels. Histopathological analysis revealed that NAC
administration, either orally or intraperitoneally, leads to a better incisional
healing in terms of inflammation, granulation, collagen deposition,
reepithelization and neovascularization. CONCLUSION: The present study supports
the hypothesis that NAC administration alleviates the negative effects of
radiotherapy on incisional wound healing by means of reducing oxidative stress
markers and improving histologic parameters independent of the route of
administration.
PMID- 25125947
TI - Prevalence and molecular epidemiology of methicillin-resistant Staphylococcus
aureus in a tertiary Greek hospital.
AB - BACKGROUND/AIM: Methicillin-resistant Staphylococcus aureus (MRSA) is a major
cause of health- and community-associated infections; its prevalence in Greece is
among the highest in Europe. We investigated the prevalence and molecular
epidemiology of MRSA in a tertiary Greek hospital. MATERIAL AND METHODS: Spa
typing and random polymorphic DNA analysis were used to investigate the molecular
epidemiology of 28 MRSA isolates during May 2010 to May 2011 in a tertiary
hospital in Northern Greece. RESULTS: Nine spa types were detected; t003 was the
predominant (32.1%) one, detected in various wards and throughout the study
period, while t037 was recovered only from intensive care unit patients, and only
in April 2011, suggestive of an epidemic. Additional rare types were detected for
the first time in Greece. CONCLUSIONS: Spa typing and random polymorphic DNA
analysis gave an insight into the epidemiology of MRSA in a Northern Greece
hospital. Concerning the distribution in the hospital, the predominant spa type
t003 was present in various wards, and was constantly detected throughout the
study period, very suggestive of an epidemic, while other types were detected
only in specific wards. Our data underline the need for surveillance, typing and
constant reassessment of existing strategies to control MRSA.
PMID- 25125948
TI - Comparison of analgesic efficiency between wound site infiltration and ultra
sound-guided transversus abdominis plane block after cesarean delivery under
spinal anaesthesia.
AB - BACKGROUND: [corrected] Local anesthetic infiltration applied on the wound site
or abdominal wall may be used for relieving postoperative pain after delivery by
caesarean section. The aim of this study was to compare the analgesic efficiency
of ultrasound (USG)-guided transversus abdominis plane (TAP) block with local
anesthetic infiltration on a wound site. METHODS: This study was designed as a
prospective randomized trial, and consisted of 70 pregnant women of American
Society of Anesthesiologists (ASA) class I-II. Patients were randomized into
Group I (wound site infiltration, n=35) and Group T (TAP block, n=35). Spinal
anaesthesia was administered to all patients. In Group I, wound site infiltration
was applied by the surgical team. In Group T, a USG-guided bilateral TAP block
was applied. Patients' numeric pain scale (NPS) levels at 2, 6, 12 and 24(th)
hours, after the operation (NPS0) and during mobilization were assessed.
Postoperative complications, time to first analgesic request and patient
satisfaction were recorded. RESULTS: The NPS0 values of Group T were found to
higher and time to first analgesic request longer than those of Group I. The NPS
values of Group I at 2, 6, 12, and 24(th) hours were found to be statistically
significantly higher than those of Group T. CONCLUSIONS: According to our
results, USG-guided TAP block might be superior to infiltration anaesthesia for
postoperative pain management of patients who have had caesarean section and it
provided longer-lasting and more efficient analgesia.
PMID- 25125949
TI - Ultrastructural aspects of the effects of L-carnitine administration on
epithelial cells in the aging rat tongue.
AB - BACKGROUND: The investigators hypothesized that degenerative changes accumulate
in epithelial cells in the aging rat tongue and that carnitine administration is
effective at reversing these alterations. MATERIAL AND METHODS: To gain insights
into the effects of carnitine on epithelial cells of the tongue, the
investigators used 15 Wistar rats [3 experimental groups: 5- (A), 12- (B) and 18-
(C) month old rats] with 4 rats per group and 1 control group with 1 rat per age
group). L-carnitine was administered intraperitoneally to animals of the
experimental group for 35 days. Samples of the tongue were processed for electron
microscopy. RESULTS: Degeneration of epithelial cells of the rat tongue was shown
to begin early in life (5 months) and alterations were shown to accumulate while
aging. L-carnitine administration eliminated degenerative changes when
administered in the first age group A, while in the older rats the regeneration
was only partial for the epithelium (groups B and C). CONCLUSIONS: The results of
this study suggest that profound ultrastructural alterations commence in the
degenerating rat tongue and that L-carnitine administration results into partial
regeneration of epithelial cells.
PMID- 25125950
TI - Effect of exhaust emissions on carbon monoxide levels in employees working at
indoor car wash facilities.
AB - BACKGROUND: Exhaust emissions from motor vehicles threaten the environment and
human health. Carbon monoxide (CO) poisoning, especially the use of exhaust gas
CO in suicidal attempts is well known in the literature. Recently, indoor car
wash facilities established in large shopping malls with closed parking, lots is
a new risk area that exposes car wash employees to prolonged periods of high
level CO emissions from cars. The aim of this study was to investigate how
carboxyhemoglobin (COHb) blood levels of employees get affected in confined areas
with relatively poor air circulation. METHODS: Twenty male volunteers working in
indoor parking car wash facilities were included in the study. Participants were
informed about the aim of this study and their consent was obtained. Their pulse
COHb levels were measured twice, at the beginning and at the end of the working
day using Rad-57 pulse CO-oximeter device, allowing non-invasive measurement of
COHb blood levels to compare the changes in their COHb levels before and after
work. RESULTS: The mean age of the male volunteers was 29.8 +/- 11.9 (range 18
55). While the mean COHb levels measured at the start of the working day was 2.1
+/- 2.0 (range 0-9), it was increased to 5.2 +/- 3.3 (range 1-15) at the end of
work shift (Wilcoxon test, p <0.001). There was a statistically significant
difference in COHb levels between the beginning and the end of the work shift in
smoker subjects, while the difference was not significant in the non-smoking
group (Wilcoxon test, p=0.001, p=0.102, respectively). CONCLUSION: The COHb blood
levels of indoor car wash facility employees is directly impacted and gets
elevated by motor vechile exhaust emissions. For the health of the employees at
indoor parking car wash facilities, stricter precautions are needed and the
government should not give permit to such operations.
PMID- 25125951
TI - Complications of automated spring fired biopsy gun technique. A retrospective
analysis of 230 cases.
AB - BACKGROUND: Renal biopsy (RB) is a procedure which allows obtaining kidney tissue
for a morphological diagnosis. As an invasive procedure, RB could lead to some
complications. The aim of the study was to assess the incidence and the severity
of various complications of renal biopsy(RB) performed by automated spring fired
biopsy gun with needles 16 and 18G. MATERIAL AND METHODS: A total number of 230
RB obtained from patients over 18 years of age, within the period from January
2009 to July 2013, were analyzed retrospectively. All RB were performed by a
standartized technique using an automated spring fired biopsy gun, with 16, and
18 G disposable needle. The average age of the patients was 45.5 +/- 22.3 years,
119 male and 111 female. As many as 170 biopsies were performed with 16 G needle
and 60 with 18G. The assessment of the early post-biopsy complications was done
by renal ultrasound (US). RESULTS: Of all RB, 92.7% were successfully performed.
In 60% of the failed RB 18 G needle was used. No post-biopsy complications were
noted in 93.4%. Hematomas were observed in 15 out of 230 cases (6.6%). Of those,
80% were assessed as minor hematomas (12/15) with an average size of 20.4mm +/-
11mm and they appeared to be asymptomatic.While 8 cases (66%) of all 12 minor
hematomas were obtained by two passes (66%), only 4 cases (34%) of hematoma were
observed after one pass <0.01. The cases of hematomas obtained with 16 G needle
were significantly higher than those in the group with 18G (8 to 4, p<0,05).
However, when the number of hematomas in both groups referred to the number of
all biopsies in the corresponding group, no significant difference of this
complication was observed, p > 0.05. The incidence of major complications was
1.3%. CONCLUSION: The optimal period for US examination of the kidneys for early
diagnosis of complications is up to 24 hours after RB. The experience of the
physician performing the procedure is of great importance for reducing the risk
of complications as well as the RB technique used. An automated spring fired
biopsy gun with needle 16G is recommended.
PMID- 25125952
TI - Postoperative analgesic effect of epidural neostigmine following caesarean
section.
AB - AIM: The aim of this study was to evaluate the analgesic effects of postoperative
epidural administration of neostigmine and morphine in patients scheduled for
caesarean section under epidural anaesthesia. MATERIAL AND METHODS: Sixty ASA I
II patients, scheduled for caesarean section under epidural anaesthesia, were
randomly allocated into three groups. Neostigmine (10 MUg/kg), morphine (3 mg),
and saline (6 mL) were administered to the neostigmine, morphine, and control
groups, respectively, 30 minutes after the surgery via the epidural catheter.
Afterwards, postoperative pain treatment was administered to all patients with a
patient-controlled epidural analgesia (PCEA) device, using 0.125% bupivacaine.
The patients were followed up for 24 hours. The total volume of local
anaesthetics used, the time to first analgesic requirement, analgesic
requirements, VAS scores, analgesia quality, first passage of bowel gas,
ambulation times, haemodynamic parameters and side effects were evaluated.
RESULTS: The time to first analgesic requirement was significantly longer in the
morphine group than in the neostigmine and control groups (p<0.01), and in the
neostigmine group compared to the control group (p<0.05). The total local
anaesthetic consumption and the number of bolus injections were significantly
higher in the control group than in the other groups (p<0.01). The first passage
of bowel gas occurred significantly sooner in the neostigmine group than in the
morphine (p<0.01) and the control (p<0.05) groups. Itching frequency was
significantly higher in the morphine group than in the other two groups (p<0.05).
VAS scores were similar in the morphine and neostigmine groups. CONCLUSION:
Postoperative single-dose epidural neostigmine reduced the 24-hour analgesic
requirements but in the chosen doses presented an analgesic effect significantly
lower than morphine. Hippokratia 2014; 18 (1): 44-48.
PMID- 25125953
TI - Effects of methylene blue in acute lung injury induced by blunt chest trauma.
AB - BACKGROUND: We studied whether methylene blue (MB) treatment blunts chest trauma
induced lung injury in rats. MATERIAL AND METHODS: Forty male Sprague-Dawley
rats, 200-300g, were used. The rats were divided into five groups (n=8): control,
early contusion (EC), early contusion + methylene blue (2 mg/kg, EC+MB), late
contusion (LC), and late contusion + methylene blue (2 mg/kg, LC+MB). RESULTS:
Histopathological analysis showed increased hemorrhage, alveolar wall thickness,
edema, and inflammatory cell infiltrates in the EC and LC rats, which decreased
upon MB treatment. Immunohistochemical studies revealed that MB reduced
activation of inducible nitric oxide synthase (iNOS) and the number of active
terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive
cells. A significant increase was observed in the malondialdehyde (MDA) and
nitric oxide (NO) levels in the EC group compared to the control group (p<0.05).
In addition, a significant decrease was reported in the glutathione (GSH),
superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels (p<0.01), but
no significant difference was observed in the catalase (CAT) levels among the
groups. The MDA level was significantly higher in the LC group compared to the
control group, whereas the GSH level was significantly lower compared to the
control group. The NO level in the EC+MB group was significantly lower when
compared to the NO level in the EC group (p<0.05). CONCLUSION: The present study
provides evidence that MB might serve as a therapeutic treatment for blunt chest
trauma.
PMID- 25125955
TI - Cricotracheal separation with multiple cricoid fractures after blunt neck injury:
a case report.
AB - BACKGROUND/AIM: Cricotracheal separation is a rare injury with fatal results in
most cases. Clear guidelines are not available and several dilemmas are to be
faced during patient management in such cases. DESCRIPTION OF CASE: We present a
case of cricotracheal separation with multiple cricoid fractures in a 16-year-old
male with blunt neck trauma. CONCLUSION: Early recognition based on an index of
clinical suspicion is necessary in order to establish this rare diagnosis.
Intervention should preserve the laryngeal function as much as possible.
PMID- 25125954
TI - Genotype 4 HCV infection is difficult to cure with pegylated interferon and
ribavirin. Results from a Greek Nationwide Cohort Study.
AB - BACKGROUND AND AIM: Patients with genotype 4 (G4) chronic hepatitis C (CHC) are
considered a difficult to treat population, although current data on G4 treatment
responsiveness and duration are controversial. Greece represents a country with
an intermediate prevalence of G4 infections, offering an opportunity to compare
treatment outcomes by genotype and to identify potential prognostic factors for
sustained virologic response (SVR). METHODS: All CHC patients from the
HepNet.Greece, an ongoing nationwide cohort study on viral hepatitis, with known
hepatitis C virus (HCV) genotype who received treatment with Peg-IFNa and
ribavirin were analyzed. RESULTS: From 4443 patients, 951 (61.7% males, 78.4%
Greeks, median age 40.6 years, 10% cirrhosis) fulfilled the inclusion criteria.
G4 was found in 125 (13.1%) patients. Genotype distribution was not significantly
different between Greeks and immigrants. Patients with G4 had similar odds of SVR
compared to G1 but significantly lower compared to G2/G3. Age, treatment
discontinuation, presence of cirrhosis and previous history of HCV-treatment were
associated with lower probabilities of SVR. Ethnicity did not affect SVR for all
genotypes while response to treatment was similar between Greek and Egyptian
patients groups (35.7% vs 40.9%, p=0.660%) with G4 infection. The relation
between SVR and genotype did not substantially change after adjustment for age,
gender, cirrhosis, treatment interruption and history of HCV-treatment.
CONCLUSIONS: The findings of this large cohort of CHC patients with a well
balanced genotype distribution further supports the idea of considering G4 as a
difficult to treat genotype. Further investigation is needed to identify genotype
specific prognostic factors.
PMID- 25125956
TI - Systemic thrombolysis with the use of tenecteplase for segmental acute renal in
farction potentially associated with multiple thrombophilic gene polymorphisms.
AB - BACKGROUND/AIM: The potential association of acute renal infarction with multiple
thrombophilic gene polymorphisms and the experience of treatment with
tenecteplase are described for the first time in the international literature.
DESCRIPTION OF THE CASE: The case of a 50-year old male with segmental acute
renal infarction potentially associated with multiple thrombophilic gene
polymorphisms is presented. He was thrombolysed with a single intravenous bolus
of tenecteplase in a weight-adjusted dose (0.53mg/Kg bodyweight). Within 30
minutes after drug administration, the patient's symptoms were completely
relieved. Patient's clinical course was uneventful with an acceptable renal
function outcome eight weeks post-treatment. The following gene polymorphisms
were identified: G455A (b-fibrinogen); C677T; A1298C (methylenetetrahydropholate
reductase); T196C (platelet glycoprotein IIIa); 4G/5G (plasminogen activator
inhibitor-1). CONCLUSION: Tenecteplase is a safe and simple to use thrombolytic,
with favourable pharmacokinetic profile, which might be useful if administered
early, especially when local thrombolysis is impossible or unavailable and
therefore warrants further investigation in clinical trials. Hippokratia 2014; 18
(1): 67-70.
PMID- 25125957
TI - A survival case of severe liver failure caused by acetylsalicylic acid that was
treated with living donor liver transplantation.
AB - BACKGROUND: Severe liver dysfunction caused by acetylsalicylic acid (ASA) is
quite rare. The purpose is to describe a patient with severe liver dysfunction
due to excessive intake of ASA in a suicide attempt, who was successfully treated
with living donor liver transplantation (LDLT). DESCRIPTION OF CASE: We report a
20-year-old woman who took 66 g of ASA in a suicide attempt. She was admitted to
our hospital and received forced alkaline diuresis. However, her liver and renal
functions worsened after admission. On the 6th day after intake of ASA, she was
transferred to the intensive care unit, and plasma exchange (PE) and continuous
hemodiafiltration were performed. Since her liver function did not recover
despite repeated PE, she was transferred to another hospital for LDLT on the 8th
day. She underwent LDLT with a portion of the liver donated from her mother on
the 11(th) day. After the operation, her renal dysfunction continued. Her renal
parameters gradually improved, and she was discharged on the 44th post-operative
day without renal dysfunction. CONCLUSION: PE is effective in removing ASA from
blood. Liver transplantation is the only effective treatment if liver function
does not recover in spite of repeated PE.
PMID- 25125958
TI - Complicated acute appendicitis within a right inguinal hernia sac (Amyand's
hernia): report of a case.
AB - BACKGROUND: The term Amyand's hernia refers to a rare clinical situation
characterized by the presence of a normal or inflammed appendix within the sac of
an inguinal hernia. The situation may be asymptomatic or may present as an
incarcerated hernia in case of strangulation or acute appendicitis occurring
inside the hernia sac. DESCRIPTION OF THE CASE: We present the case of a right
Amyand's hernia on a 88-years-old male that presented to our emergency department
with a severely tender and swollen inguinal mass that was diagnosed as a
strangulated inguinal hernia - inguinal abcess and underwent emergency operation.
The intraoperative findings included a severely inflamed and perforated appendix
along with healthy part of the caecum inside the sac. Appendectomy with
subsequent primary hernia repair without mesh was performed with excellent
outcome. CONCLUSION: Because of the fact that most of such rare cases are managed
by urgent surgery with no preoperative diagnosis, every surgeon should be
prepared for the possibility of coping with such an unexpected situation.
PMID- 25125959
TI - A case of surgical instrument left in the abdomen and taken out of the transverse
colon.
AB - BACKGROUND: Foreign bodies cause an aseptic reaction that does not have specific
symptoms and may also result in peritonitis, acute abdominal pain, an
intraperitoneal abscess, or intestinal obstruction or perforation. We present a
case of a surgical instrument left in the abdomen that passed into the transverse
colon via migration after a surgery. CASE DESCRIPTION: A 36-year-old female
patient was operated upon, with a diagnosis of a hydatid cyst in her liver.
Approximately 3 years after the surgery, she excreted part of a surgical forceps
with her stool while she was defecating. In upright direct abdominal radiography,
a surgical instrument was observed in the abdomen. The patient was operated to
remove the foreign body from the abdomen. The surgical instrument that was taken
out had corroded and turned black. It was observed that the material that had
dropped out of the anus and the material that was taken out during the operation
were parts of the same surgical instrument. The ascending colon and the abdomen
were stitched anatomically. Follow-ups were conducted after the operation, and
the patient was discharged with recovery. CONCLUSIONS: It should be noted that a
surgical instrument may be left inside the body of patients who have a history of
surgery and that it can migrate.
PMID- 25125960
TI - A case report of retroperitoneal extrahepatic hepatocellular carcinoma presented
with elevated level of Alpha fetoprotein.
AB - BACKGROUND: High level of alpha-fetoprotein is usually associated with testis
cancer or hepatocellular carcinoma a primary tumor of the liver. CASE: We report
the case of a 72-year-old male patient with chronic renal failure who presented
with a high alpha-fetoprotein (AFP) level and a retroperitoneal mass, which was
subsequently diagnosed to be an extrahepatic hepatocellular carcinoma.
CONCLUSION: A retroperitoneal mass with elevated AFP level and no detected liver
lesions is not always caused by a testicular cancer.
PMID- 25125961
TI - Unusual histological patterns and hyaline ring granulomas in a unicystic
ameloblastoma.
AB - BACKGROUND: Unicystic ameloblastoma (UA) is a distinct variant of ameloblastoma
displaying a large cystic cavity lining by ameloblastomatous epithelium and can
present a wide variety of histologic patterns. CASE REPORT: We herein reported an
unusual UA occurring in the mandible of a 23-year-old male patient who exhibited
luminal, intraluminal and mural patterns, as well as acanthomatous, basal cells
and granular cell variants. In addition, hyaline ring granulomas, an
extraordinary finding in ameloblastoma, were found. The nature of several
microscopic variants in this tumor and the possible significance of their
presence have also been discussed. CONCLUSIONS: We believe this to be the first
case reported in which a UA displayed multiplicity of histopathological patterns
in a single lesion.
PMID- 25125962
TI - De Quervain thyroiditis in the course of H1N1 influenza infection.
AB - BACKGROUND/AIM: Viral infections have been frequently associated with subacute
(De Quervain) thyroiditis and autoimmune thyroid diseases. In the present case
report we document a rare case of De Quervain thyroiditis in the course of H1N1
influenza infection. DESCRIPTION OF THE CASE: A 17-year-old previously healthy
female that was treated in the General Hospital of Kalamata developed an
influenza-like syndrome that was accompanied by palpitations, thyroid
enlargement, and increased C-reactive protein. Polymerase chain reaction assay
confirmed the diagnosis of H1N1 virus infection. Serum thyroid-stimulating
hormone was suppressed to zero while the levels of free thyroxine and
triiodothyronine were increased. The patient was treated with non-steroidal anti
inflammatory drugs and thyroid function was gradually restored without evolving
to a hypothyroid phase. CONCLUSION: To our knowledge this is the second case
described in the literature of De Quervain thyroiditis associated with H1N1
influenza infection.
PMID- 25125963
TI - Cystic lymphangioma of the inguinal and scrotal regions in childhood - report of
three cases.
AB - BACKGROUND: [corrected] Cystic lymphangiomas are congenital lymphatic
malformations that most commonly develop in the neck, axilla, mediastinum and
retroperitoneum. Inguinal and scrotal lymphangiomas are extremely rare. CASES
REPORT: We present the cases of three children with cystic lymphangiomas that
were treated in our department during a two year period. The patients were all
boys, aged 3.5, 9 and 13 years, and the location of the cystic lymphangioma was
the scrotum, the inguinal region and the epididymis respectively. Clinical
examination and ultrasonography described the lesions as cystic. Surgical
excision of the lesions with a testis-sparing approach was performed in all three
cases and histopathology set the diagnosis of cystic lymphangiomas. Complementary
imaging of the regions adjacent to the excised lesions, excluded any extension or
co-existing lesions. Post-operative period was uneventful and during a follow-up
period of six months all patients were well with no signs of recurrence.
CONCLUSIONS: Scrotal and inguinal cystic lymphangiomas are treated with surgical
excision with care to preserve the intra-scrotal structures and the structures of
the inguinal canal. Complete excision is necessary to prevent recurrence.
Complementary imaging of the adjacent regions is necessary to identify any
possible extension or co-existing lesions.
PMID- 25125964
TI - Purple Urine Bag Syndrome: a case report of an alarming phenomenon.
AB - BACKGROUND: Purple urine bag syndrome is an uncommon phenomenon where the plastic
urinary catheter bag and tubing turn purple. It occurs in some elderly
constipated chronic urinary catheterization patients. The phenomenon is
attributed to the presence of metabolites of tryptophan in the presence of
urinary tract infection.This urine discoloration may lead to misdiagnosis and
also cause great concern to patients and their relatives. CASE REPORT: We present
the clinical case of a 83-year-old female patient with dementia and
hypothyroidism, chronically catheterized, who presented with purple-color urine
initially misdiagnosed as having haematuria.
PMID- 25125965
TI - Alpha heavy chain disease: a rare lymphoma hard to diagnose.
PMID- 25125966
TI - Osteosarcoma in an adolescent previously treated for Hodgkin's Disease.
PMID- 25125967
TI - An In-depth Analysis of a Multilocus Phylogeny Identifies leuS As a Reliable
Phylogenetic Marker for the Genus Pantoea.
AB - Partial sequences of six core genes (fusA, gyrB, leuS, pyrG, rlpB, and rpoB) of
37 strains of Pantoea species were analyzed in order to obtain a comprehensive
view regarding the phylogenetic relationships within the Pantoea genus and
compare tree topologies to identify gene(s) for reliable species and subspecies
differentiation. All genes used in this study were effective at species-level
delineation, but the internal nodes represented conflicting common ancestors in
fusA- and pyrG-based phylogenies. Concatenated gene phylogeny gave the expected
DNA relatedness, underscoring the significance of a multilocus sequence analysis.
Pairwise comparison of topological distances and percent similarities indicated a
significant differential influence of individual genes on the concatenated tree
topology. leuS- and fusA-inferred phylogenies exhibited, respectively, the lowest
(4) and highest (52) topological distances to the concatenated tree. These
correlated well with high (96.3%) and low (64.4%) percent similarities of leuS-
and fusA-inferred tree topologies to the concatenated tree, respectively. We
conclude that the concatenated tree topology is strongly influenced by the gene
with the highest number of polymorphic and non-synonymous sites in the absence of
significant recombination events.
PMID- 25125968
TI - iteRates: An R Package for Implementing a Parametric Rate Comparison on
Phylogenetic Trees.
AB - Patterns of diversification rate variation detected in phylogenetic hypotheses
are frequently used to infer historical, ecological, and evolutionary processes.
The parametric rate comparison (PRC) is a method for detecting rate variation in
trees that models branch lengths as random variables drawn from familiar
statistical distributions. iteRates is a library of functions for the R
statistical computing environment for implementing PRC on phylogenetic trees.
Here, we describe some of the functions in iteRates for subtree identification,
tree manipulation, applying the PRC and K-clades PRC analyses, and conducting a
whole-tree randomization test.
PMID- 25125969
TI - Integrative Pathway Analysis Using Graph-Based Learning with Applications to TCGA
Colon and Ovarian Data.
AB - Recent method development has included multi-dimensional genomic data algorithms
because such methods have more accurately predicted clinical phenotypes related
to disease. This study is the first to conduct an integrative genomic pathway
based analysis with a graph-based learning algorithm. The methodology of this
analysis, graph-based semi-supervised learning, detects pathways that improve
prediction of a dichotomous variable, which in this study is cancer stage. This
analysis integrates genome-level gene expression, methylation, and single
nucleotide polymorphism (SNP) data in serous cystadenocarcinoma (OV) and colon
adenocarcinoma (COAD). The top 10 ranked predictive pathways in COAD and OV were
biologically relevant to their respective cancer stages and significantly
enhanced prediction accuracy and area under the ROC curve (AUC) when compared to
single data-type analyses. This method is an effective way to simultaneously
predict binary clinical phenotypes and discover their biological mechanisms.
PMID- 25125970
TI - Hydroxyproline, a serum biomarker candidate for gastric ulcer in rats: a
comparison study of metabolic analysis of gastric ulcer models induced by
ethanol, stress, and aspirin.
AB - Gastrointestinal symptoms are a common manifestation of adverse drug effects. Non
steroid anti-inflammatory drugs (NSAIDs) are widely prescribed drugs that induce
the serious side effect of gastric mucosal ulceration. Biomarkers for these side
effects have not been identified and ulcers are now only detectable by endoscopy.
We previously identified five metabolites as biomarker candidates for NSAID
induced gastric ulcer using capillary electrophoresis-mass spectrometry (CE-MS)
based metabolomic analysis of serum and stomach from rats. Here, to clarify
mechanism of changes and limitations of indications of biomarker candidates, we
performed CE-MS-based metabolomic profiling in stomach and serum from rats with
gastric ulcers induced by ethanol, stress, and aspirin. The results suggest that
a decrease in hydroxyproline reflects the induction of gastric injury and may be
useful in identifying gastric ulcer induced by multiple causes. While
extrapolation to humans requires further study, hydroxyproline can be a new serum
biomarker of gastric injury regardless of cause.
PMID- 25125971
TI - Molecular and Kinetic Characterization of Babesia microti Gray Strain Lactate
Dehydrogenase as a Potential Drug Target.
AB - Babesia microti is an emerging zoonotic protozoan organism that causes "malaria
like" symptoms that can be fatal in immunocompromised people. Owing to lack of
specific therapeutic regiment against the disease, we cloned and characterized B.
microti lactate dehydrogenase (BmLDH) as a potential molecular drug receptor. The
in vitro kinetic properties of BmLDH enzyme was evaluated using nicotinamide
adenine dinucleotide (NAD(+)) as a co-factor and lactate as a substrate.
Inhibitory assay was also done using gossypol as BmLDH inhibitor to determine the
inhibitory concentration 50 (IC50). The result showed that the 0.99 kbp BmLDH
gene codes for a barely soluble 36 kDa protein (332 amino acids) localized in
both the cytoplasm and nucleus of the parasite. In vitro enzyme kinetic studies
further revealed that BmLDH is an active enzyme with a high catalytic efficiency
at optimal pH of 10.2. The K m values of NAD(+) and lactate were 8.7 +/- 0.57 mM
and 99.9 +/- 22.33 mM, respectively. The IC50 value for gossypol was 0.345 MUM,
while at 2.5 MUM, gossypol caused 100% inhibition of BmLDH catalytic activity.
These findings, therefore, provide initial evidence that BmLDH could be a
potential drug target, although further in vivo studies are needed to validate
the practical application of lactate dehydrogenase inhibitors against B. microti
infection.
PMID- 25125972
TI - Memory Decline in Peri- and Post-menopausal Women: The Potential of Mind-Body
Medicine to Improve Cognitive Performance.
AB - Cognitive decline is a frequent complaint during the menopause transition and
among post-menopausal women. Changes in memory correspond with diminished
estrogen production. Further, many peri- and post-menopausal women report sleep
concerns, depression, and hot flashes, and these factors may contribute to
cognitive decline. Hormone therapy can increase estrogen but is contraindicated
for many women. Mind-body medicine has been shown to have beneficial effects on
sleep, mood, and hot flashes, among post-menopausal women. Further, mind-body
medicine holds potential in addressing symptoms of cognitive decline post
menopause. This study proposes an initial framework for how mind-body
interventions may improve cognitive performance and inform future research
seeking to identify the common and specific factors associated with mind-body
medicine for addressing memory decline in peri- and post-menopausal women. It is
our hope that this article will eventually lead to a more holistic and
integrative approach to the treatment of cognitive deficits in peri- and post
menopausal women.
PMID- 25125973
TI - Subcutaneously administered methotrexate for rheumatoid arthritis, by prefilled
syringes versus prefilled pens: patient preference and comparison of the self
injection experience.
AB - PURPOSE: This multicenter, randomized, crossover study compared preference, ease
of use, acceptability, satisfaction, and safety of repeated subcutaneous (SC)
self-administrations with prefilled pens and prefilled syringes delivering
methotrexate (MTX), in patients with rheumatoid arthritis (RA). PATIENTS AND
METHODS: The study (ClinicalTrials.gov number NCT01793259) enrolled 120 patients
requiring initiation or intensification of MTX therapy for RA. Patients were
randomized to receive the test drug, a prefilled pen (Metex((r))
PEN/Metoject((r)) PEN), or the reference drug, a prefilled syringe
(Metex((r))/Metoject((r))), at doses of 15, 17.5, or 20 mg MTX SC once a week for
3 weeks. This was followed by receipt of the reference drug (prefilled syringe)
or the test drug (prefilled pen) in a crossover design, with each patient serving
as his/her own control. Questionnaires regarding patient preference, the Self
Injection Assessment Questionnaire (SIAQ), and diaries regarding local
tolerability were used to document outcomes. RESULTS: Overall patient preference
for the MTX prefilled pen was 75% (P<0.0001). In a six-item questionnaire, 73% to
76% of the patients preferred the prefilled pen in relation to use,
acceptability, and satisfaction, and 67% of the patients confirmed that it did
not take much effort to overcome SC self-injection with the pen. The SIAQ showed
no clinical differences, in any domain scores, between both devices. Overall
patient attitude towards self-injection at baseline was positive, as was patient
experience with both devices during the study. As well, 92% of physicians and
study nurses indicated that they would recommend the MTX prefilled pen to
patients for future MTX treatment. The formulations were generally well
tolerated. CONCLUSION: SC self-injection of MTX with a prefilled pen was
generally preferred, by patients with RA, over a prefilled syringe with regard to
use, acceptability, and satisfaction. This is supported by the strong
appreciation of their attending study nurses and physicians, for its convenience.
PMID- 25125975
TI - Serum cytokine profiling and enrichment analysis reveal the involvement of
immunological and inflammatory pathways in stable patients with chronic
obstructive pulmonary disease.
AB - Chronic obstructive pulmonary disease (COPD) is a major global health problem. It
results from chronic inflammation and causes irreversible airway damage. Levels
of different serum cytokines could be surrogate biomarkers for inflammation and
lung function in COPD. We aimed to determine the serum levels of different
biomarkers in COPD patients, the association between cytokine levels and various
prognostic parameters, and the key pathways/networks involved in stable COPD. In
this study, serum levels of 48 cytokines were examined by multiplex assays in 30
subjects (control, n=9; COPD, n=21). Relationships between serum biomarkers and
forced expiratory volume in 1 second, peak oxygen uptake, body mass index,
dyspnea score, and smoking were assessed. Enrichment pathways and network
analyses were implemented, using a list of cytokines showing differential
expression between healthy controls and patients with COPD by Cytoscape and
GeneGo MetacoreTM software (Thomson-Reuters Corporation, New York, NY, USA).
Concentrations of cutaneous T-cell attracting chemokine, eotaxin, hepatocyte
growth factor, interleukin 6 (IL-6), IL-16, and stem cell factor are
significantly higher in COPD patients compared with in control patients. Notably,
this study identifies stem cell factor as a biomarker for COPD. Multiple
regression analysis predicts that cutaneous T-cell-attracting chemokine, eotaxin,
IL-6, and stem cell factor are inversely associated with forced expiratory volume
in 1 second and peak oxygen uptake change, whereas smoking is related to eotaxin
and hepatocyte growth factor changes. Enrichment pathways and network analyses
reveal the potential involvement of specific inflammatory and immune process
pathways in COPD. Identified network interaction and regulation of different
cytokines would pave the way for deeper insight into mechanisms of the disease
process.
PMID- 25125974
TI - Influence of diet and obesity on COPD development and outcomes.
AB - The global increase in the prevalence and incidence of obesity has called serious
attention to this issue as a major public health concern. Obesity is associated
with many chronic diseases, including cardiovascular disease and diabetes, and
recently the role of overweight and obesity in lung disease has received new
interest. Independently of obesity, diet also plays a role as a risk factor for
many chronic diseases, and evidence is accumulating to support a role for diet in
the prevention and management of several lung diseases. Chronic obstructive lung
disease is the third-leading cause of death globally, and both obesity and diet
appear to play roles in its pathophysiology. Obesity has been associated with
decreased lung-function measures in population-based studies, with increased
prevalence of several lung diseases and with compromised pulmonary function. In
contrast, obesity has a protective effect against mortality in severe chronic
obstructive pulmonary disease (COPD). Nutrient intake and dietary patterns have
also been associated with lung-function measures and the development and
progression of COPD. Taken together, this suggests that a focus on obesity and
diet should be part of public health campaigns to reduce the burden of lung
disease, and could have important implications for clinicians in the management
of their patients. Future research should also focus on elucidating these
relationships in diverse populations and age-groups, and on understanding the
complex interaction between behavior, environment, and genetics in the
development and progression of COPD. The goal of this article is to review
current evidence regarding the role that obesity and diet play in the development
of COPD, and in COPD-related outcomes.
PMID- 25125978
TI - Support for the initial attachment, growth and differentiation of MG-63 cells: a
comparison between nano-size hydroxyapatite and micro-size hydroxyapatite in
composites.
AB - Hydroxyapatite (HA) is considered to be a bioactive material that favorably
influences the adhesion, growth, and osteogenic differentiation of osteoblasts.
To optimize the cell response on the hydroxyapatite composite, it is desirable to
assess the optimum concentration and also the optimum particle size. The aim of
our study was to prepare composite materials made of polydimethylsiloxane,
polyamide, and nano-sized (N) or micro-sized (M) HA, with an HA content of 0%,
2%, 5%, 10%, 15%, 20%, 25% (v/v) (referred to as N0-N25 or M0-M25), and to
evaluate them in vitro in cultures with human osteoblast-like MG-63 cells. For
clinical applications, fast osseointegration of the implant into the bone is
essential. We observed the greatest initial cell adhesion on composites M10 and
N5. Nano-sized HA supported cell growth, especially during the first 3 days of
culture. On composites with micro-size HA (2%-15%), MG-63 cells reached the
highest densities on day 7. Samples M20 and M25, however, were toxic for MG-63
cells, although these composites supported the production of osteocalcin in these
cells. On N2, a higher concentration of osteopontin was found in MG-63 cells. For
biomedical applications, the concentration range of 5%-15% (v/v) nano-size or
micro-size HA seems to be optimum.
PMID- 25125979
TI - High-sensitivity C-reactive protein, lipoprotein-related phospholipase A2, and
acute ischemic stroke.
AB - BACKGROUND: Serum biomarkers may be useful for early diagnosis of acute ischemic
stroke, exclusion of other diseases that may mimic stroke, and prediction of
infarct volume. We evaluated serum high-sensitivity C-reactive protein (hs-CRP)
and lipoprotein-related phospholipase A2 (Lp-PLA2) in patients who had acute
ischemic stroke. METHODS: In 200 patients who presented to an emergency service
(acute ischemic stroke, 102 patients; control with no stroke, 98 patients),
stroke patients were evaluated with the Canadian neurological scale and diffusion
weighted magnetic resonance imaging, and all patients were evaluated with the
Glasgow coma scale and their serum hs-CRP level and Lp-PLA2 activity were
assessed. The volume of stroke lesions was calculated from magnetic resonance
images. RESULTS: Patients who had stroke had higher mean serum hs-CRP level
(stroke, 7+/-6 mg/dL; control, mean +/- standard deviation 1+/-1 mg/dL; P<=0.001)
and Lp-PLA2 activity (stroke, mean +/- standard deviation 113+/-86 nmol/min/mL;
control, mean +/- standard deviation 103+/-50 nmol/min/mL; P<=0.001) than control
patients who did not have stroke. The mean hs-CRP level and Lp-PLA2 activity were
higher in patients who had greater stroke severity (lower Canadian neurological
scale score) and were higher in patients who had larger volume strokes.
CONCLUSION: Higher hs-CRP level and Lp-PLA2 activity are significantly associated
with more severe neurologic impairment and larger infarct size in patients who
have acute ischemic stroke. These biomarkers may be useful for rapid diagnosis
and prediction of ischemic tissue volume in the early stage of ischemic stroke.
These findings may be important for health care facilities that have limited
access to emergency computed tomography scanning for the diagnosis of stroke.
PMID- 25125976
TI - Update on the pathological processes, molecular biology, and clinical utility of
N-acetylcysteine in chronic obstructive pulmonary disease.
AB - Chronic obstructive pulmonary disease (COPD) is a common and morbid disease
characterized by high oxidative stress. Its pathogenesis is complex, and involves
excessive oxidative stress (redox imbalance), protease/antiprotease imbalance,
inflammation, apoptosis, and autoimmunity. Among these, oxidative stress has a
pivotal role in the pathogenesis of COPD by initiating and mediating various
redox-sensitive signal transduction pathways and gene expression. The protective
physiological mechanisms of the redox balance in the human body, their role in
the pathogenesis of COPD, and the clinical correlation between oxidative stress
and COPD are reviewed in this paper. N-acetylcysteine (NAC) is a mucolytic agent
with both antioxidant and anti-inflammatory properties. This paper also reviews
the use of NAC in patients with COPD, especially the dose-dependent properties of
NAC, eg, its effects on lung function and the exacerbation rate in patients with
the disease. Earlier data from BRONCUS (the Bronchitis Randomized on NAC Cost
Utility Study) did not suggest that NAC was beneficial in patients with COPD,
only indicating that it reduced exacerbation in an "inhaled steroid-naive"
subgroup. With regard to the dose-dependent properties of NAC, two recent
randomized controlled Chinese trials suggested that high-dose NAC (1,200 mg
daily) can reduce exacerbations in patients with COPD, especially in those with
an earlier (moderately severe) stage of disease, and also in those who are at
high risk of exacerbations. However, there was no significant effect on symptoms
or quality of life in patients receiving NAC. Further studies are warranted to
investigate the effect of NAC at higher doses in non-Chinese patients with COPD.
PMID- 25125980
TI - Breast cancer characteristics and survival in a Hispanic population of costa
rica.
AB - BACKGROUND: Breast cancer characteristics may vary according to the patient's
ethnic group. The goal of this cohort study was to evaluate the characteristics
of a group of Costa Rican breast cancer patients and their relationship with
survival. METHODS: Age, stage, tumor grade, immunohistochemistry, lymphovascular
invasion, recurrence, and survival data on 199 Hispanic patients with breast
cancer diagnosis, treated between January 2009 and May 2010, were collected from
a single institution in San Jose, Costa Rica. The data were statistically
analyzed for significance. RESULTS: Median age at diagnosis was 53 years. With a
median follow-up of 46.5 months, there was an 88% overall survival rate. Thirty
seven percent of the patients (p < 0.001) were at stages III and IV during
diagnosis. The hormone receptor human epidermal receptor negative phenotype (HR
HER2-) (p < 0.001) was present in 17% of the cases. In a multivariate analysis,
local (risk ratio, RR: 7.2; confidence interval, CI 95%: 3.8-7.6; p = 0.06) and
distant recurrence (RR: 14.9; CI 95%: 7.7-28.9; p = 0.01) showed the strongest
association with the probability of death from the disease. Patients with HR-HER2
phenotype tumors reported more local recurrences (p = 0.04), a higher tumor
grade (p < 0.01), and lower overall survival than patients with other breast
cancer phenotypes (p = 0.01). CONCLUSIONS: Although this study analyzes a modest
number of cases, it is an initial insight into factors that may contribute to
differences in breast cancer outcomes among Hispanic women in Costa Rica. The
higher proportion of triple negative tumors, advanced stage, and younger median
age at diagnosis could contribute to the inferior prognostic described among
Hispanic women. There may be a different distribution of tumor subtypes compared
to non-Hispanic white women. Further studies are necessary to confirm such
findings.
PMID- 25125977
TI - Cellular trafficking and anticancer activity of Garcinia mangostana extract
encapsulated polymeric nanoparticles.
AB - Garcinia mangostana Linn extract (GME) is a natural product that has received
considerable attention in cancer therapy, and has the potential to reduce side
effects of chemotherapeutics and improve efficacy. We formulated GME-encapsulated
ethyl cellulose (GME-EC) and a polymer blend of ethyl cellulose and methyl
cellulose (GME-EC/MC) nanoparticles. We achieved high drug-loading and
encapsulation efficiency using a solvent-displacement method with particle sizes
around 250 nm. Cellular uptake and accumulation of GME was higher for GME
encapsulated nanoparticles compared to free GME. In vitro cytotoxicity analysis
showed effective anticancer activity of GME-EC and GME-EC/MC nanoparticles in
HeLa cells in a dose-dependent manner. GME-EC/MC nanoparticles showed
approximately twofold-higher anticancer activity compared to GME-EC
nanoparticles, likely due to their enhanced bioavailability. GME-encapsulated
nanoparticles primarily entered HeLa cells by clathrin-mediated endocytosis and
trafficked through the endolysosomal pathway. As far as we know, this is the
first report on the cellular uptake and intracellular trafficking mechanism of
drug-loaded cellulose-based nanoparticles. In summary, encapsulation of GME using
cellulose-derivative nanoparticles - GME-EC and GME-EC/MC nanoparticles -
successfully improved the bioavailability of GME in aqueous solution, enhanced
cellular uptake, and displayed effective anticancer activity.
PMID- 25125982
TI - Breast Positioning during Mammography: Mistakes to be Avoided.
AB - AIMS AND OBJECTIVES: Breast positioning is the key factor affecting a mammogram.
If care is taken during positioning, it maximizes the amount of breast tissue
being imaged, eliminates most of the artifacts, and increases sensitivity of the
mammogram. This retrospective study was carried out in our department to assess
correctness, and also the incorrectness of breast positioning, which need to be
avoided to obtain an ideal mammogram. MATERIAL AND METHODS: A total of 1369
female patients were included in this study. Mammography was performed on full
field detector digital mammography equipment. Craniocaudal (CC) view and
mediolateral oblique (MLO) view were carried out for each breast. Four views were
done for 1322 patients. The remaining 47 patients had undergone a mastectomy and
underwent two views for the other breast. Mistakes in improperly positioned
mammogram were assessed with respect to proper visualization of nipple, position
of pectoralis major, pectoral-nipple distance (PND), inframammary fold, and
adequate coverage of all breast quadrants. RESULTS: As per prescribed guidelines,
mistakes in positioning were recognized in 2.879% of total mammograms. Improper
positioning of the nipple was the commonest problem, seen in 3.827% of
mammograms, CC view. On MLO view, bilaterally, pectoralis shadow was not seen in
0.520% mammograms, its margin was not straight/convex in 0.706%, lower edge of
pectoralis was above pectoralis-nipple line in 2.081%, and inframammary fold was
not seen in 1.189%. There was inadequate coverage of lower quadrants in 2.787%,
and mismatch in PND was seen in 3.864%. In few of the patients, the shortcomings
as a result of improper positioning were noted on one view, the rest being
normal. CONCLUSION: Positioning is the most important factor affecting the
resultant mammography image. During mammography, many cases are improperly
positioned and as a result the examination is inconclusive, which reduces the
sensitivity of mammography.
PMID- 25125981
TI - Current Approaches and Emerging Directions in HER2-resistant Breast Cancer.
AB - Human epidermal growth factor receptor-2 (HER2) is overexpressed in up to 30% of
breast cancers; HER2 overexpression is indicative of poor prognosis. Trastuzumab,
an anti-HER2 monoclonal antibody, has led to improved outcomes in patients with
HER2-positive breast cancer, including improved overall survival in adjuvant and
first-line settings. However, a large proportion of patients with breast cancer
have intrinsic resistance to HER2-targeted therapies, and nearly all become
resistant to therapy after initial response. Elucidation of underlying mechanisms
contributing to HER2 resistance has led to development of novel therapeutic
strategies, including those targeting HER2 and downstream pathways, heat shock
protein 90, telomerase, and vascular endothelial growth factor inhibitors.
Numerous clinical trials are ongoing or completed, including phase 3 data for the
mammalian target of rapamycin inhibitor everolimus in patients with HER2
resistant breast cancer. This review considers the molecular mechanisms
associated with HER2 resistance and evaluates the evidence for use of evolving
strategies in patients with HER2-resistant breast cancer.
PMID- 25125983
TI - Improvement of quality and safety in health care as a new interprofessional
learning module - evaluation from students.
AB - BACKGROUND: Interprofessional teamwork is in many ways a norm in modern health
care, and needs to be taught during professional education. DESCRIPTION: This
study is an evaluation of a newly introduced and mandatory learning module where
students from different health profession programs used Improvement of Quality
and Safety as a way to develop interprofessional competence in a real-life
setting. The intention of this learning module was to integrate interprofessional
teamwork within the students' basic education, and to give students a basic
knowledge about Improvement of Quality and Safety. This report focuses on
evaluations from the participating students (n=222), mainly medical and nursing
students. MATERIALS AND METHODS: To evaluate this new learning module, a
questionnaire was developed and analyzed using a mixed methods design,
integrating both qualitative and quantitative methods. The evaluation addressed
learning concepts, learning objectives, and interprofessional and professional
development. RESULTS AND CONCLUSION: A majority of students responded positively
to the learning module as a whole, but many were negative towards specific parts
of the learning module and its implementation. Medical students and male students
were less positive towards this learning module. Improvements and alterations
were suggested.
PMID- 25125984
TI - Pediatricians' perceptions of clinical practice guidelines.
AB - BACKGROUND: Clinical practice guidelines (CPGs) are propositions for health care
providers about the care of patients and are usually described as "systematically
developed statements to assist practitioners' and patients' decisions about
appropriate health care for specific circumstances". OBJECTIVES: The purpose of
this study was to investigate pediatricians' perceptions of clinical practice
guidelines at Hamad Medical Corporation (HMC) in Qatar. METHODS: A cross
sectional study was conducted at HMC between May 1 and August 31, 2013 using a
self-administered questionnaire that was distributed to 240 pediatricians.
RESULTS: A total of 169/240 questionnaires were completed for a response rate of
70.4%. Our main finding was that pediatricians at all levels are familiar with
CPGs and use them. In addition, our doctors believe that CPGs lead to good
quality of care, are practical, provide standardized patient care, will keep them
up-to-date, decrease the rate of litigation, are evidence-based, do not restrict
continuity of self-education, do not alter physician esteem, lead to improvement
of outcome, and are practical. However, barriers that might impede pediatricians'
use of CPGs are that CPGs affect their clinical judgment, do not match with their
practice style, and do not reduce health care costs. CONCLUSIONS: Pediatricians
at HMC have positive perceptions of CPGs. The results of our study suggest that
CPGs are likely to be implemented if more counseling and education are provided
to pediatricians regarding the usefulness of evidence-based guidelines. In
addition, a program should be initialized to remove barriers while simultaneously
addressing physicians' concerns.
PMID- 25125987
TI - Use of frameless intrauterine devices and systems in young nulliparous and
adolescent women: results of a multicenter study.
AB - BACKGROUND: The purpose of this study was to provide additional data on the
experience with frameless copper and levonorgestrel (LNG) intrauterine devices
(IUDs) in nulliparous and adolescent women. METHODS: Nulliparous and adolescent
women, 25 years of age or younger, using the frameless copper IUD or the
frameless LNG-releasing intrauterine system (IUS), were selected from previous
studies and a current multicenter post-marketing study with the frameless copper
IUD. The small copper-releasing GyneFix((r)) 200 IUD consists of four copper
cylinders, each 5 mm long and only 2.2 mm wide. The frameless FibroPlant((r)) LNG
IUS consists of a fibrous delivery system releasing the hormone levonorgestrel
(LNG-IUS). The main features of these intrauterine contraceptives are that they
are frameless, flexible, and anchored to the fundus of the uterus. RESULTS: One
hundred and fifty-four nulliparous and adolescent women participated in the
combined study. One pregnancy occurred with the GyneFix 200 IUD after unnoticed
early expulsion of the device (cumulative pregnancy rate 1.1 at one year). Two
further expulsions were reported, one with the GyneFix 200 IUD and the other with
the FibroPlant LNG-IUS. The cumulative expulsion rate at one year was 1.1 with
the copper IUD and 2.2 with the LNG-IUS. The total discontinuation rate at one
year was low (3.3 and 4.3 with the copper IUD and LNG-IUS, respectively) and
resulted in a high rate of continuation of use at one year (96.7 with the copper
IUD and 95.7 with the LNG-IUS, respectively). Continuation rates for both
frameless copper IUD and frameless LNG-IUS remained high at 3 years (>90%). There
were no cases of perforations or pelvic inflammatory disease reported during or
following insertion. CONCLUSION: This report confirms earlier studies with
frameless devices and suggests that the high user continuation rate is
attributable to the optimal relationship between the IUD and the uterine cavity.
IUD studies have shown that an IUD that does not fit well will often lead to side
effects (ie, pain, bleeding, embedment, expulsion) and subsequent removal of the
IUD. Early discontinuation is not the aim of long-acting reversible
contraception.
PMID- 25125986
TI - Hyperemesis gravidarum: current perspectives.
AB - Hyperemesis gravidarum is a complex condition with a multifactorial etiology
characterized by severe intractable nausea and vomiting. Despite a high
prevalence, studies exploring underlying etiology and treatments are limited. We
performed a literature review, focusing on articles published over the last 10
years, to examine current perspectives and recent developments in hyperemesis
gravidarum.
PMID- 25125988
TI - Incidence and risk of infection in egyptian patients with systemic lupus
erythematosus.
AB - BACKGROUND: Infection in systemic lupus erythematosus (SLE) is common and is one
of the leading causes of morbidity and mortality. OBJECTIVE: To study the risk
and occurrence of infection in Egyptian SLE patients and to determine its
characteristics. METHODS: A total of 200 SLE patients were followed up for 1 year
at monthly intervals, undergoing clinical and laboratory evaluation. Disease
activity was assessed by SLE disease activity measurement (SLAM) score.
Infections were diagnosed on basis of clinical findings, medical opinion,
positive blood and urine cultures, Gram stain results, and specific serological
assays as measurement of CMV and EBV antibodies. RESULTS: A total of 55% of
patients developed infection, 45% had one infection, and the rest had multiple
infection episodes. Total number of infections was 233 infections/year, 47.2%
were major and 52.8% were minor infections. Urinary tract was the most commonly
involved site with bacterial infection being the commonest isolated organism
(46.4%), and E. coli the commonest isolated bacteria (14.2%). There were 51
episodes caused by systemic viral infection (CMV in 25, EBV in 22, HCV in 3, and
1 in HBV). CONCLUSION: There is a high rate of infection among SLE patients.
Disease activity, leukopenia, high CRP level, positive anti-dsDNA, consumed C3,
and cyclophosphamide therapy are independent risk factors for infection in SLE.
PMID- 25125989
TI - Do we have to perform a renal biopsy? Clinical dilemmas in a case with nephrotic
syndrome.
AB - Renal biopsy is one of the pivotal diagnostic tools used in the field of
nephrology. A morphological analysis of the kidney may also be of value for the
overall management of patients with diabetic nephropathy. However, the
indications for renal biopsy differ considerably among nephrologists, and no
global consensus regarding performing this procedure among diabetic patients with
various renal manifestations has yet been achieved. In this report, we would like
to describe our serendipitous experience with a male type 2 diabetic patient
presenting with nephrotic syndrome complicated by concurrent gastric carcinoma.
We also discuss several conundrums that arose in the current case, which had an
impact on our diagnostic and therapeutic decisions.
PMID- 25125985
TI - Epidemiology of human African trypanosomiasis.
AB - Human African trypanosomiasis (HAT), or sleeping sickness, is caused by
Trypanosoma brucei gambiense, which is a chronic form of the disease present in
western and central Africa, and by Trypanosoma brucei rhodesiense, which is an
acute disease located in eastern and southern Africa. The rhodesiense form is a
zoonosis, with the occasional infection of humans, but in the gambiense form, the
human being is regarded as the main reservoir that plays a key role in the
transmission cycle of the disease. The gambiense form currently assumes that 98%
of the cases are declared; the Democratic Republic of the Congo is the most
affected country, with more than 75% of the gambiense cases declared. The
epidemiology of the disease is mediated by the interaction of the parasite
(trypanosome) with the vectors (tsetse flies), as well as with the human and
animal hosts within a particular environment. Related to these interactions, the
disease is confined in spatially limited areas called "foci", which are located
in Sub-Saharan Africa, mainly in remote rural areas. The risk of contracting HAT
is, therefore, determined by the possibility of contact of a human being with an
infected tsetse fly. Epidemics of HAT were described at the beginning of the 20th
century; intensive activities have been set up to confront the disease, and it
was under control in the 1960s, with fewer than 5,000 cases reported in the whole
continent. The disease resurged at the end of the 1990s, but renewed efforts from
endemic countries, cooperation agencies, and nongovernmental organizations led by
the World Health Organization succeeded to raise awareness and resources, while
reinforcing national programs, reversing the trend of the cases reported, and
bringing the disease under control again. In this context, sustainable
elimination of the gambiense HAT, defined as the interruption of the transmission
of the disease, was considered as a feasible target for 2030. Since rhodesiense
HAT is a zoonosis, where the animal reservoir plays a key role, the interruption
of the disease's transmission is not deemed feasible.
PMID- 25125990
TI - Schwannoma of the median nerve: diagnosis sometimes delayed.
AB - Schwannoma is a tumor that develops from nerve sheath. The authors report an
unusual case of schwannoma of the median nerve (MN) that remained asymptomatic
for four years. The diagnosis was based on MRI (magnetic resonance imaging) and
histopathological examination. Surgical removal is usually curative. The
asymptomatic character of the tumor and its slow evolution remain an essential
factor in diagnosis delays. This tumor has a good prognosis with a low recurrence
rate and potential for malignant transformation.
PMID- 25125993
TI - "When was the last tiame you do something for the first time" part 2.
PMID- 25125991
TI - Age and menopausal status affect osteoprotegerin and osteocalcin levels in women
differently, irrespective of thyroid function.
AB - Osteoprotegerin (OPG) and osteocalcin (OC) are essential bone proteins. Recent
studies have demonstrated that they are not secreted solely by bone cells; they
play roles in the vascular function and energy metabolism, and they are
influenced by multiple factors. The aim of the current study was to investigate
the influence of menopause and age on OPG and OC in women with different thyroid
stimulating hormone (TSH) levels. MATERIAL AND METHODS: We studied 49 women with
elevated TSH, 26 with suppressed TSH, and 67 age-matched euthyroid controls. Of
them 64 were menstruating and 78 postmenopausal. Body weight, height, waist
circumference (WC), body mass index (BMI), serum TSH, free thyroxin (FT4), OPG,
and OC were measured. RESULTS: Generally, both OPG and OC were higher in the
postmenopausal women than in the menstruating subjects (OPG 3.85 +/- 1.49 pmol/L
vs. 5.84 +/- 2.42 pmol/L, P < 0.001; OC 8.84 +/- 3.70 ng/dL vs. 12.87 +/- 6.45
ng/dL, P < 0.001), and within the two thyroid dysfunction subgroups and the
controls (all P < 0.05). OPG correlated with age (postmenopausal rho = 0.57, P <
0.001; premenopausal rho = 0.31, P = 0.015). Among the premenopausal subjects,
OPG was higher in those with low TSH than in the controls (P = 0.048). OC
correlated negatively with BMI and WC in the postmenopausal group (Spearman rho =
-0.25, P = 0.03 and rho = -0.42, P < 0.001 respectively). OC was higher in the
postmenopausal subjects with low TSH than in those with elevated TSH (P = 0.024),
and correlated positively with FT4 (rho = 0.40, P = 0.002) and negatively with
TSH (rho = -0.29, P = 0.013). CONCLUSIONS: In women, OPG and OC depended
differently on age and menopause and, to a lesser extent, on the thyroid function
and body composition.
PMID- 25125994
TI - Nuclear accident crisis and liver disease: a summary on evidences.
AB - The present global concern is on the adverse effect due to exposure to nuclides
expelled from the disrupted nuclear power plant accident in Japan. The exposure
can induce several adverse effects. In this specific brief review, the author
summarizes the evidences on the effect on liver. Discussion is focused on several
liver diseases.
PMID- 25125992
TI - Biomimetic electrospun nanofibrous structures for tissue engineering.
AB - Biomimetic nanofibrous scaffolds mimicking important features of the native
extracellular matrix provide a promising strategy to restore functions or achieve
favorable responses for tissue regeneration. This review provides a brief
overview of current state-of-the-art research designing and using biomimetic
electrospun nanofibers as scaffolds for tissue engineering. It begins with a
brief introduction of electrospinning and nanofibers, with a focus on issues
related to the biomimetic design aspects. The review next focuses on several
typical biomimetic nanofibrous structures (e.g. aligned, aligned to random,
spiral, tubular, and sheath membrane) that have great potential for tissue
engineering scaffolds, and describes their fabrication, advantages, and
applications in tissue engineering. The review concludes with perspectives on
challenges and future directions for design, fabrication, and utilization of
scaffolds based on electrospun nanofibers.
PMID- 25125995
TI - Tc-99m mebrofenin hepatobiliary scan in obstructive hepatobiliary disease:
determining causes with early and late delayed imaging.
AB - Hepatobiliary radionuclide imaging is typically performed to detect
cholecystitis. Infrequently, imaging reveals an obstructive pattern. Although
delayed hepatobiliary imaging is commonly used to differentiate between
intrahepatic (IH) and extrahepatic (EH) obstruction in the newborn; there is room
to clarify the use of delayed imaging in the adult population. A retrospective
review was performed of adult patients demonstrating a complete obstructive
pattern on initial Tc-99m mebrofenin hepatobiliary imaging. Delayed imaging was
divided into early delayed (ED) (<10 h) and late delayed (LD) (>=10 h) imaging.
Two physicians qualified the presence of intestinal radiotracer (negative, low to
high) on delayed images. Determination of EH or IH pathology was obtained from
chart review. A total of 24 patients demonstrated an obstructive pattern using
delayed Tc-99m mebrofenin hepatobiliary imaging, with delayed imaging ranging
from 4 to 30 h. EH pathologies (choledocholithiasis, stricture, other)
represented 63% of cases (n = 15), IH pathologies (cirrhosis, hepatitis, other)
represented 33% cases (n = 8) and 1 case was indeterminate. 67% of EH cases
showed intestinal activity on delayed imaging (67% on ED and 67% on LD imaging),
whereas 63% of IH cases showed intestinal activity on delayed imaging (67% on ED
imaging and 60% on LD imaging). The presence of intestinal activity on the both
the early and delayed images did not differentiate between the IH and EH
pathology groups. Subdividing the groups into ED imaging and LD imaging was also
not predictive of determining location of obstructive pattern on the initial 1 h
of imaging. This data suggests that delayed hepatobiliary scintigraphy has little
or no role in determining the cause of obstructive pathology.
PMID- 25125996
TI - Factors predicting treatment failure in patients treated with iodine-131 for
graves' disease.
AB - Treatment of Graves' disease with iodine-131 ((131)I) is well-known; however, all
patients do not respond to a single dose of (131)I and may require higher and
repeated doses. This study was carried out to identify the factors, which can
predict treatment failure to a single dose of (131)I treatment in these patients.
Data of 150 patients with Graves' disease treated with 259-370 MBq of (131)I
followed-up for at least 1-year were retrospectively analyzed. Logistic
regression analysis was used to predict factors which can predict treatment
failure, such as age, sex, duration of disease, grade of goiter, duration of
treatment with anti-thyroid drugs, mean dosage of anti-thyroid drugs used,
(99m)Tc-pertechnetate ((99m)TcO4 (-)) uptake at 20 min, dose of (131)I
administered, total triiodothyronine and thyroxine levels. Of the 150 patients,
25 patients required retreatment within 1 year of initial treatment with (131)I.
Logistic regression analysis revealed that male sex and (99m)TcO4 (-) uptake were
associated with treatment failure. On receiver operating characteristic (ROC)
curve analysis, area under the curve (AUC) was significant for (99m)TcO4 (-)
uptake predicting treatment failure (AUC = 0.623; P = 0.039). Optimum cutoff for
(99m)TcO4 (-) uptake was 17.75 with a sensitivity of 68% and specificity of 66%
to predict treatment failure. Patients with >17.75% (99m)TcO4 (-) uptake had odds
ratio of 3.14 (P = 0.014) for treatment failure and male patients had odds ratio
of 1.783 for treatment failure. Our results suggest that male patients and
patients with high pre-treatment (99m)TcO4 (-) uptake are more likely to require
repeated doses of (131)I to achieve complete remission.
PMID- 25125997
TI - Empiric Therapy with Low-Dose I-131 in Differentiated Cancer Thyroid: What is the
Magic Number?
AB - Low dose radioactive iodine-131 (RAI) has been widely reported in the treatment
of patients with differentiated thyroid cancer (DTC) since 1970's. However, the
clinical outcomes, dosage of I-131 and criteria for successful ablation are
different in various studies. The aim of this study was to assess clinical
outcome 18-month after RAI therapy in selected DTC patients and identify factors
associated with a good response. In this experimental study, among patients with
DTC referred to the Nuclear Medicine Department and had an indication for RAI
therapy in the period between December 2008 and January 2011, 108 subjects were
selected randomly. The patients were randomly divided into three groups and
empiric low dose therapy with 30, 50 or 75 mCi of I-131 was administered.
Patients were monitored closely clinically and with serum thyroglobulin assays
and I-131 whole-body scans at 6 monthly intervals for 18-month after treatment.
Among 105 patients who completed follow-up, 86% were successfully ablated with a
single low dose of I-131. There was no statistically significant difference in
ablation rates in the subgroups receiving 30.50 or 75 mCi of I-131. Cumulative
ablation rate was 99% in patients after the second dose of low dose therapy. If
appropriate selection criteria are used in DTC, successful remnant ablation can
be achieved with low doses of I-131 in the range of 30-75 mCi. No significant
differences were found in results achieved with 30.50 or 75 mCi of I-131. As the
majority of the DTC patients fall within the inclusion criteria of this study,
they can be treated on an ambulatory basis with associated low cost, convenience,
and low whole-body radiation-absorbed dose to the patients.
PMID- 25125998
TI - Autonomous Functioning Thyroid Nodule in a 4-year-old Male Child Treated with
Radioiodine (I-131).
AB - Autonomous functioning thyroid nodules that cause toxic manifestations (toxic
adenomas) are benign monoclonal tumors characterized by their capacity to grow
and produce thyroxine (T4) and triiodothyronine (T3) autonomously, i.e. in the
absence of thyrotropin thyroid stimulating hormone. Toxic adenomas are a rare
presentation of hyperthyroidism in the pediatric population. Radioiodine (I-131)
has been widely used for therapy of patients with toxic adenomas and is now
accepted as a safe and effective treatment even in the pediatric age group. The
authors here present a case of a 4-year-old boy with a solitary hyperfunctioning
thyroid nodule, who was successfully treated with radioiodine (I-131) and is
presently on follow-up.
PMID- 25125999
TI - F-18 fluorodeoxyglucose positron emission tomography/computed tomography in the
staging of linitis plastica caused by primary gastric adenocarcinoma.
AB - Diffuse infiltration by a primary or metastatic malignancy into the submucosa and
muscularis of the stomach (linitis plastica [LP]) has been described in
literature. The authors present a case of LP caused by primary adenocarcinoma of
the stomach, showing diffuse Fluorine-18 fluorodeoxyglucose uptake in the
thickened wall of the stomach.
PMID- 25126000
TI - Vesicoureteral Reflux Detected on Post-void Image of (99m)Tc MAG3 Renal
Scintigraphy.
AB - (99m)Tc MAG3 scintigraphic scan is sensitive at depicting focal parenchymal
abnormalities and can be used for the measurement of overall renal function. We
experienced a 5-year-old boy presenting with bilateral flank fain, intermittent
urinary stream and dysuria. On the post-void delayed image of (99m)Tc MAG3
scintigraphic scan vesicoureteral reflux was detected in left non-functioning
kidney, which was missed on voiding cystourethrography.
PMID- 25126002
TI - False-positive (111)In-pentetreotide Uptake in Gastritis.
AB - (111)In-pentetreotide [(111)In-octreoscan] is the most widely used radiolabeled
somatostatin analog for evaluating neuroendocrine tumor overexpression of
somatostatin receptors. False-positives studies of somatostatin receptor
scintigraphy have been reported and often the cause is unexplained but assumed to
be due to high number of somatostatin receptors in other pathologies. Causes of
false-positives include visualization of the gallbladder, nasal mucosa and
pulmonary hilar areas in respiratory infections, thyroid abnormalities, accessory
spleens, recent Cerebrovascular accidents (CVA's) and activity at the site of a
recent surgical incision. In infection or inflammation the cause of false
positive uptake is probably the result of tracer binding by somatostatin
receptors on the inflammatory leukocytes. In this case report, we report, a 44
year-old male patient with false-positive (111)In-pentetreotide uptake due to
gastritis.
PMID- 25126003
TI - Routine whole volume single photon emission tomography reconstruction in
comparison to cine raw data in the detection of extracardiac uptake.
PMID- 25126001
TI - Bone scanning in the adductor insertion avulsion syndrome.
AB - A thigh splint (adductor insertion avulsion syndrome) is a relatively uncommon
diagnosis analogous to shin splints. This article reports a 19-year-old female
patient NOT a regular athlete who presented with groin pain. Physical examination
was non-specific; magnetic resonance imaging pelvis did not reveal any
abnormality. Patient referred for whole body bone scan, especially to locate any
abnormality in the spine. This study highlights the role of whole body bone scan
in the evaluation of groin pain and importance of evaluation of whole lower
extremity.
PMID- 25126004
TI - The role of plasma gelsolin in cardiopulmonary bypass induced acute lung injury
in infants and young children: a pilot study.
AB - BACKGROUND: Acute lung injury (ALI) induced by cardiopulmonary bypass (CPB, CPB
ALI) is a common and serious complication after cardiac surgery. And infants and
young children are more prone to CPB-ALI. The purpose of this study was to
investigate the perioperative changes of plasma gelsolin (pGSN) in patients below
3 years of age with cardiac surgeries and CPB, and determine whether pGSN are
associated with the occurrence and severity of CPB-ALI. METHODS: Seventy-seven
consecutive patients <=3 years of age with congenital heart diseases (CHD)
performed on open heart surgery with CPB were finally enrolled, and assigned to
ALI and non-ALI groups according to the American-European Consensus Criteria.
Plasma concentrations of gelsolin and total protein were measured at following 8
time points: before CPB (a), after CPB (b), 2 hours after CPB (c), 6 hours after
CPB (d), 12 hours after CPB (e), 24 hours after CPB (f), 48 hours after CPB (g)
and 72 hours after CPB (h). RESULTS: Twenty-seven (35.1%) patients developed CPB
ALI in the study, including eleven (14.3%) patients with ARDS. The earliest
significant drop of pGSN and normalized pGSN (pGSNN) of ALI group both occurred
at 6 hours after CPB (p = 0.04 and p < 0.01), which was much earlier than those
of non-ALI group (48 hours, p = 0.03 and 24 hours, p < 0.01); PGSN of ALI group
before CPB and 6 hours after CPB were both significantly lower than those of non
ALI group (p < 0.01); PGSNN of ALI group before CPB and 6 hours after CPB were
both significantly lower than those of non-ALI group (p < 0.01, p = 0.04); PGSN
before CPB was the only independent risk factor predicting the occurrence of CPB
ALI (OR, 1.023; 95% CI, 1.007-1.039; p < 0.01) with an AUC of 0.753 (95% CI,
0.626-0.880); The optimal cutoff value of pGSN before CPB was 264.2 mg/L, with a
sensitivity of 58.3% and a specificity 94.7%. And lower pGSN before CPB was
significantly associated with the severity of CS-AKI (r = -0.45, p < 0.01).
CONCLUSIONS: Patients developing CPB-ALI had lower plasma gelsolin reservoir and
a much more amount and rapid consumption of plasma gelsolin early after
operation. PGSN before CPB was an early and sensitive predictor of CPB-ALI in
infants and young children undergoing cardiac surgery, and was negatively
correlated with the severity of CPB-ALI.
PMID- 25126006
TI - Combined hysterolaparoscopy for the diagnosis of female infertility: a
retrospective study of 132 patients in china.
AB - OBJECTIVES: To evaluate the effects and safeness of combined hysterolaparoscopy
on evaluation the causes of infertility. METHODS: This retrospective study was
conducted at the Department of Gynecology (The Third Affiliated Hospital of Sun
Yat-Sen University, Guangzhou, Guangdong, China) from January 2011 to April 2014.
Patients aged 21-43 years with infertility were included in this study. The
prevalence of different lesions was collected to analyze. RESULTS: 132 infertile
patients were included, 71 (53.8%) women had primary infertility and the rest 61
(46.2%) had secondary infertility. Laparoscopic abnormalites were more common
than hysteroscopy abnormalites both in primary infertility group and secondary
infertility group. Pelvic inflammatory disease (59.09 %) and endometriosis
(29.55%) were the most common abnormalities in two groups. The most common
intrauterine pathology was uterine polyps and the most common uterine
malformation was uterine septum in two groups. Out of 12 patients having
malformation uterus, only one was double uterus and double cervical with double
vagina. There was no major surgical or anesthetic complication in any of our
patients, other than mild abdominal pain. CONCLUSION: Hysterolaparoscopy is an
effective and safe tool in comprehensive evaluation of infertility to diagnosis
and treat the lesions of pelvic and uterus in the same time. Hysterolaparoscopy
may be recommended as the first and final procedure for evaluation of female
infertility.
PMID- 25126007
TI - Prevalence and factors associated with congenital malformations in tirana,
Albania, during 2011-2013.
AB - AIM: Congenital Malformations (CMs) represent a challenge especially for
developing countries. Data about CMs in Albania are rather scarce. In this
context, our aim was to assess the prevalence and factors associated with CMs in
Tirana, the capital of Albania. METHODS: Information on all CMs at birth during
2011-2013 was retrieved from the National CM Surveillance System. For each CM
case, three controls (babies born without CM) were retrieved as well. Overall,
831 cases and 2522 controls were included in this study. The prevalence was
calculated using the total number of live births in Tirana during the same
period. Binary logistic regression was used to determine the factors associated
with CMs adjusting for a number of covariates. RESULTS: The three-year prevalence
of CMs was 23.41 per 1,000 live births. The most affected body systems were the
musculoskeletal, cardiovascular and genital systems. CMs were more prevalent
among male babies. Advanced mothers' age, lower education, unemployment status
and lower gestational age were all positively associated with increased
likelihood of CMs. CONCLUSIONS: Socio-demographic factors of mothers are linked
to CMs in Albania. Future surveys are needed in Albania in order to establish
determinants of CMs at a national level.
PMID- 25126005
TI - Challenging dedifferentiated liposarcoma identified by MDM2-amplification, a
report of two cases.
AB - BACKGROUND: Liposarcoma is the most frequent soft tissue sarcoma. Well
differentiated liposarcoma may progress into dedifferentiated liposarcoma with
pleomorphic histology. A minority additionally features myogenic, osteo- or
chondrosarcomatous heterologous differentiation. Genomic amplification of the
Mouse double minute 2 homolog (MDM2) locus is characteristic for well
differentiated and dedifferentiated liposarcomas. Detection of MDM2 amplification
may supplement histopathology and aid to distinguish liposarcoma from other soft
tissue neoplasia. CASE PRESENTATION: Here we present two cases of
dedifferentiated liposarcoma with challenging presentation. Case 1 features a
myogenic component. As the tumour infiltrated the abdominal muscles and showed
immunohistochemical expression of myogenic proteins, rhabdomyosarcoma had to be
ruled out. Case 2 has an osteosarcomatous component resembling extraosseous
osteosarcoma. The MDM2 status was determined in both cases and helped making the
correct diagnosis. Overexpression of MDM2 and co-overexpression of Cyclin
dependent kinase 4 is demonstrated by immunohistochemistry. The underlying MDM2
amplification is shown by fluorescence in situ hybridisation. Since low grade
osteosarcoma may also harbour MDM2 amplification it is emphasised that the
amplification has to be present in the lipomatous parts of the tumour to
distinguish liposarcoma from extraosseous osteosarcoma. CONCLUSIONS: The two
cases exemplify challenges in the diagnoses of dedifferentiated liposarcoma.
Liposarcoma often has pleomorphic histology and additionally may feature
heterologous components that mimic other soft tissue neoplasms. Amplification of
MDM2 is characteristic for well differentiated and dedifferentiated liposarcomas.
Determination of the MDM2 status by in situ hybridisation may assist
histopathology and help to rule out differential diagnoses.
PMID- 25126008
TI - The Role of CT Angiography of Coronaries in Early Diagnosis of Coronary Artery
Plaques in Albanian People with No History of Cardiovascular Disease in
Correlation with Traditional Risk Factors.
AB - OBJECTIVE: To evaluate the role of CT angiography of coronaries (CTAC) in the
diagnosis of subclinical atherosclerosis by detection of coronary artery plaques
(CAP) in a group of consecutive albanian individuals with no history of coronary
artery disease (CAD) or acute coronary syndrome and to investigate the relation
between the prevalence of CAP, traditional risk factors and the expected 10-year
risk of fatal cardiovascular event (CVE) based on our own experience. METHOD AND
TECHNIQUE: This is a prospective study including 456 patients with no history of
CAD who underwent CTAC in our hospital from September 2009 to March 2013. Risk
estimation of fatal CVE was assessed using Systematic Coronary Risk Evaluation
(SCORE) and then CT scan was performed with a 64 detector CT, including Ca Score
and angiography of coronaries with iv contrast. RESULTS: From 456 patients 61.4%
were low risk and 32.9% were at intermediate risk according to SCORE. The
prevalence of CAP diagnosed by CTAC was calculated as 55.7 % overall. Though the
presence and severity of CAP increased significantly with the increase of SCORE,
it was found to be 44.1% in the low risk patients and 80% in the intermediate
risk group, with a presence of 17% and 25% of stenotic plaques (>50%)
respectively. Significant correlation was found between all traditional risk
factors and CAP. CONCLUSION: Although a direct relation between the prevalence of
CAP, risk factors and the related 10-year risk of fatal CVE was found, there was
a significant prevalence of CAP in low -intermediate risk group with a
considerable presence of stenotic lesions. Also 8.3% of patients with no risk
factors and 18% of the patients with Ca score 0 had CAP in CT angiography, one
resulting with severe stenosis. Our results suggest once more that CT angiography
is a reliable, very accurate noninvasive technique for the diagnosis of early
CAD, especially in the low-intermediate risk patients compared to the traditional
evaluation schemes and Ca score, thus should be considered in this group as a
diagnostic guide for optimal therapy planning.
PMID- 25126009
TI - An epidemiological study on trigger factors and quality of life in psoriatic
patients.
AB - OBJECTIVE: to evaluate the role of stress, tobacco, drugs, infections, allergies,
heredity, alcohol, hormones and skin aggressions as trigger factors and the
impact on quality of life in a sample of psoriasis patients. METHODS: a
transversal study performed in 90 patients affected by psoriasis between January
and November 2012 at the "Nene Tereza" University Hospital, Tirane, Albania,
based on two scored questionnaires. RESULTS: more than 70 % of patients reported
that stressful events caused a flare- up of their psoriasis (p< 0.05). More than
60% of males and 20% of females were smokers (p< 0.05). About 20% of our patients
were taking one or more of the medications listed in the questionnaire (p> 0.05).
About 20% of patients reported having had recurrent infections (p<0,05). About
80% of males patients consumed alcohol (p<0,05). More than 40% reported a
relative with psoriasis. Statistical comparison of the group that reported skin
aggressions with the group that did not revealed a significant difference
(p<0,05). Only a few of them reported to have allergies (p>0,05). About 36% of
females reported that hormonal changes (puberty and menopause) exacerbated their
psoriasis (p<0,05). More than 40% of patients reported that psoriasis seriously
affects their quality of life. CONCLUSION: stress, tobacco, infections, heredity,
alcohol, hormonal changes and skin aggressions were confirmed as trigger factors
for psoriasis in the present sample. Allergies and the investigated drugs seemed
not to have any influence in flare-ups. We found that psoriasis had a serious
impact in the quality of life in over of 40% of the patients interviewed.
PMID- 25126011
TI - Spatial analysis and geographic variation of fatal and injury crashes in
mazandaran province from 2006 to 2010.
AB - BACKGROUND: Road safety and traffic accidents change in time and space. Although,
time variations have always been considered the subject being focused by
researchers, the effect of spatial correlation and spatial components on the risk
of accident have been less investigated. Due to its specific geographical
position, Mazandaran Province is one of the highest traffic provinces. This study
aims to investigate the factors influencing suburban crashes of Mazandaran
province by considering the spatial correlation. METHODS: This study is
aggregated (descriptive -analytical) and the study period was 2006 to 2010.
Social and environmental factors effects on the risk of accidents have been
studied considering the correlation structure of the regions and regardless of
this structure with Poisson regression, negative binomial and Full Bayes
hierarchical models. Geographical pattern of risk distribution for the observed
values of SMRs and the estimated values after smoothing have been plotted and
analyzed. RESULTS: Comparing the measures of models goodness of fit indicates
that hierarchical Bayes model fits the data better. Plotting the geographical
pattern, the north central parts of the province have been identified as the high
risk areas. Human factors were identified as the important factors for the risk
of accident. CONCLUSIONS: The purpose of this procedure is to separate the random
effect of residuals correlation. Using this method, the measure of the model
goodness of fit got reduced reflecting a better model than the prototype model.
The significance of the structured spatial effect shows the existence of unknown
explanatory variables with correlated structure whose identification and control
can reduce the risk of accidents.
PMID- 25126010
TI - Analysis of effect of antiviral therapy on regression of liver fibrosis in
patient with HCV infection.
AB - BACKGROUND: HCV infection is characterized by a tendency towards chronicity.
Acute HCV infection progresses to chronic infection in 70% of cases. Hepatitis C
virus infection can cause progressive liver injury and lead to fibrosis and
eventually cirrhosis. The degree of histologic fibrosis is an important marker of
the stage of the disease. One of current standard treatment for CHC infection is
the combination of PEG-IFN alpha and ribavirin. OBJECTIVES: The aim of the study
was to investigate the effect of the therapy with Peginterferon alfa-2a or alfa
2b plus Ribavirin on evolution of liver fibrosis in patients with chronic
hepatitis C. Also, our aim was to examine whether there was a difference between
the genders in the efficacy of these antiviral therapy. Our goal also was to
determine effect of the therapy with Peginterferon alfa-2a or alfa-2b plus
Ribavirin on evolution of liver steatosis in patients with chronic hepatitis C.
PATIENTS AND METHODS: A retrospective study was made of chronic hepatitis C
patients who had been treated from 2005 to April 2014 at the Clinic of
Gastroenterohepatology, Clinical Center University of Sarajevo. We reviewed 40
patient medical records to collect demographic, epidemiological and clinical
information, as information on liver biopsies that was performed prior to the
antiviral therapy and FibroScan((r)) test that was performed after the antiviral
therapy. For the processing of data SPSS (Statistical Package for the Social
Sciences Program) for Windows, ver. 21.0 statistical software was used.
Comparisons between qualitative and quantitative variables were performed using
the Student t-test. Mann Whitney U test was used to compare differences in
variables such as fibrosis stage and steatosis grade. A value of p<0.05 was
considered as statistically significant. RESULTS: After treatment, there was a
statistically significant increase in the number of patients with no fibrosis
(p<0.05). There was no statistically significant reduction in the number of
patients with cirrhosis (F4) (p>0.05). There was significantly higher decrease of
fibrosis progression at the patients that were in an mild-to-moderate fibrosis
(F1/F2/F3), patients that were in advanced stage of fibrosis (F4) at the time of
the pre-treatment did not have a statistically significant fibrosis reduction. We
found significant association in evolution of fibrosis after treatment with PEG
IFN alpha2a (40) kD and PEG-IFNalpha2a (12,5) kD with ribavirin (p< 0.05). We
also found significant association in evolution of steatosis after treatment with
PEG-IFN alpha2a (40) kD and PEG-IFNalpha2a (12,5) kD with ribavirin (p < 0.05).
There was statistically significant differences (p<0.05) between genders within
fibrosis qualitative evolution. CONCLUSIONS: There were significant regression of
fibrosis especially at the patients that were in an mild-to-moderate fibrosis
(F1/F2/F3), patients that were in advanced stage of fibrosis (F4) at the time of
the pre-treatment did not have a statistically significant fibrosis reduction
after treatment with PEG-IFN alpha2a (40) kD and PEG-IFNalpha2b (12,5) kD with
ribavirin. Our results showed significant improvement in steatosis in patients
infected with HCV after treatment with PEG-IFN alpha2a (40) kD and PEG-IFNalpha2b
(12,5) kD with ribavirin. Those results provides further evidence for direct
involvement of HCV and antiviral therapy in the pathogenesis of hepatic
steatosis. Female gender showed a higher degree of fibrosis reduction.
PMID- 25126012
TI - A Cross-sectional Study of Midwives' Perspectives Towards their Professional
Educational Needs.
AB - BACKGROUND: Midwives are one of the most important health care providers and
meeting their professional educational needs can be effective in maternal and
child health promotion. AIM: The aim of this study was to investigate the
midwives' perspectives towards their educational needs. METHODS: In this cross
sectional study which was conducted in 2012 in Sari, North of Iran, 223 midwives
during a convenience sampling method expressed their educational needs. The
instrument of the data collection was a self-administered 64-question researcher-
made questionnaire about the participants' educational needs in 10 fields related
to midwifery profession. RESULTS: The mean age and employment record of the
participants were 33.87+/-10.49 and 10.09+/-8.14 years respectively, and the
majority (65.02%) of them was employed in the health care centers. Findings
showed that the highest score of midwives' educational need was related to need
to education about labor and delivery care (75.14+/-21.13%) which was followed by
the need to education about pre marriage counseling (74.04+/-19.95%) and pre
conception counseling (71.33+/-21.89%). CONCLUSIONS: Owing to the emergence of
new dimensions of tasks in midwifery practice and due to developing some changes
in the educational needs of midwives, it's necessary to implement an updated
educational package in order to deliver the recommended standards of care and to
increase midwives' participation in continuing education programs.
PMID- 25126013
TI - Effect of cigarette smoking in pregnancy on infants anthropometric
characteristics.
AB - AIM: The main goal of this research is to correlate anthropometric
characteristics of newborns in pregnant women who consume cigarettes during
pregnancy. The study was conducted at the Obstetrics Clinic of the Clinical
Center, University of Sarajevo. METHODS: The retrospective study covered a period
of two years. Main inclusion criteria for the study was that pregnant women
consume cigarettes during pregnancy. The research included respondents who had a
singleton pregnancy, without pathological conditions that can affect the outcome
and duration of pregnancy. RESULTS: At the Obstetrics Clinic, Clinical Center
University of Sarajevo in the period from January 1, 2012 to December 31, 2013.
In that period 393 pregnant women completed labor who in the personal history had
data on smoking during pregnancy. Of the total number of subjects enrolled in
this study 38.17% smoked up to 10 cigarettes a day, 33.08 % smoked up to 20
cigarettes a day, while up to 30 cigarettes per day smoked 28.75 % of
respondents. CONCLUSION: There was a significant difference in the average values
of all anthropometric parameters, in relation to the number of cigarettes
consumed by the subjects during the day. We also found negative correlation in
the average values of anthropometric measures and the number of cigarettes
consumed (p <0.05).
PMID- 25126014
TI - Rates and Indicators for Episiotomy in Modern Obstetrics - a study from Saudi
Arabia.
AB - BACKGROUND: This observational study aimed to describe the rates and indicators
for practice of episiotomy during normal labour and to compare them between women
who have had one pregnancy (PG) and women who have already delivered two or more
children (G2 and above). METHODS: The study was conducted at Mother and Child
Hospital, Buraidah from October- December 2013 as a descriptive cross sectional
study. RESULTS: Overall rate of Episiotomy was 51.20%. Amongst the Primigravidas
all went through episiotomies however in G2 and above only 7 patients (4.69%)
delivered with episiotomy. Proportions tests revealed that there were significant
differences between gravidity groups on two indications of episiotomy (vaginal
breech p <0.001 and previous history of perineal tear p < 0.001). G2 and above
had episiotomy for breech delivery (1 of 7 = 14.29%) significantly more often
than PG participants (0 of 142 = 0.0%). And G2 and above participants experienced
episiotomy for previous perineal tear (2 of 7 = 28.5% as compared to none in PG
No other significant differences were found on indications of episiotomy.
CONCLUSION: Episiotomy is a very common obstetric intervention (51.20%). The PG
experience episiotomy significantly more often than G2 and above women. Efforts
should be made to reduce its rates. This can be done by reviewing the indications
and rates at repeated intervals and setting guidelines for these indications.
PMID- 25126016
TI - Situational analysis of human resources in family physician program: survey from
iran.
AB - INTRODUCTION: Family physician is the increasing efforts to promote physician and
other human resources in the health care systems. GOAL: Investigate Human
resources situation of the family physician program in six pilot cities in
Khuzestan province in the southwest of Iran. METHODS: A cross-sectional
descriptive study was conducted to examine the family physician program in 2011.
In this study, 15 healthcare teams in six pilot cities in Iran were assessed.
Data was compiled from family physician officer document in vice treatment of
Ahwaz University of medical sciences. National instructions of family physician
was used to identify current gaps. RESULTS: The survey findings indicated that
there is a doctor's shortage about 36% in the health team that deployed in the
first level of referral system. Also on the team, the 34% shortage of nurses and
60% shortages of nutrition personnel are seen. Specialists with offices in cities
of second referral level, there have not welcomed the program. CONCLUSIONS: It
seems that to facilitate patient access to physicians under contract with family
physician program and the referral system in level two and level three, adopting
arrangements to attract specialists and improving their maintenance is necessary.
PMID- 25126017
TI - Siege of town and establishment of field hospital.
AB - INTRODUCTION: The degree of material and social development determines the basic
characteristics of warfare. There are various causes, means and goals of warfare.
From the standpoint of international war law, significant is the division between
international and non-international (civil) war. International law of war is a
part of public international law and constitutes a set of contractual and legal
rules governing the relations between the international recognized subjects in
times of armed conflict. The town of Konjic and Konjic municipalities are
geographically located in the northern part of Herzegovina-Neretva Canton. It is
the largest urban municipality in the state of Bosnia and Herzegovina. Distance
to some settlements in the northeast to the northwest or the villages are 186 km.
Municipality area is 1,101 km(2). According to the character of the mountainous
districts, inhabited by a sparse population, which amounts to 29.65 people per 1
km(2). A third of the population lives in the city and suburbs, and the other two
thirds is the rural population. GOAL: Our aim was to show that in an environment,
space, under the conditions imposed suddenly by all sorts of war blockade, the
successful in transformation from peacetime to war organization, with full
support to local personnel and material-technical resources can be achieved
successful results. MATERIAL AND METHODS: This research was conducted as a
clinical, descriptive and retrospective, by valid documentation of War Hospital
and already published thesis on a series of conferences, symposia and seminars at
home and abroad. In this paper we show our results achieved in the care and
treatment of injured and sick hospitalized in the War Hospital Konjic for the
period from April 1992 till December 1995. RESULTS AND DISCUSSION: Of the total
number of hospitalized at the surgical ward, 62% had an injury, a disease had
30.7%. Dominated by war injuries (78.9%). The total mortality in the surgical
ward was 4.5%. By localization were most often represented injuries of the
extremities (52.1%), followed by chest (22.4%), stomach (13.4%), head and neck
(12.1%), and multiple wounds (10.4%). In case of extremity injury in 64% of cases
it was a case of fracture of the bone and the skeleton, and 19.5% had an injury
of the neuro-vascular structures. In case of injuries to the abdomen, usually it
was a case of open injury (95%). CONCLUSION: War Hospital, in many cases of
illness and injury, due to the proximity of combat operations, and all manner of
constant blockade, uniting all four echelons of health care by war-surgical
doctrine. Start the application of the doctrine of original beginning of the
admission, triage departments and ending at the other hospital departments with
definitive cure in 90% of cases. In the meantime, patients went through all the
stages (diagnosis, resuscitation, surgical treatment, conservative treatment,
isolation, etc.).
PMID- 25126015
TI - Perception of Societal Stigma and Discrimination Towards People Living with
HIV/AIDS in Lagos, Nigeria: a Qualitative Study.
AB - INTRODUCTION: The perception of People Living with HIV/AIDS (PLWHAs) on how the
public feels about them could influence their willingness to seek medical care,
interaction with the society and their coping strategies. MATERIAL AND METHODS:
This study assessed the perception and behavior of PLWHAs towards societal stigma
and discrimination in Lagos, Nigeria. This was a qualitative, descriptive cross
sectional study among PLWHAs from three of the three senatorial districts in
Lagos State selected using simple random sampling. Six focus group discussions
(FGDs), consisting of eight eligible respondents each were held using structured
FGD guide. RESULTS: Collected data were analyzed using simple content analysis.
About three quarter of all the discussants said life had become miserable
following episodes of stigma and discrimination against their personality in
public, family, health care settings and the work-place. Some had feelings of
guilt and depression towards these actions. About three quarter had coped with
the situation by living a low-keyed lifestyle, dissociating themselves from the
public and avoiding seeking care in HIV care centers. Majority of respondents
were not willing to come out to publicly discuss their positive HIV status for
fear of discrimination. CONCLUSION: Discussants recommended continuous awareness
campaigns about HIV to further educate the general public towards reduction of
societal stigma and discrimination against PLWHAs.
PMID- 25126018
TI - Studying the rate and causes of discharge against medical advice in hospitals
affiliated to mazandaran university of medical sciences.
AB - INTRODUCTION: Discharge against medical advice from the hospital is an important
issue from point of view of treatment management, health costs as well as the
side effects of treatment stop on patients and their accompanying. Therefore,
health managers and planners should consider the predisposing factors that change
patient's mind in this regard. Since, there has been no study to carefully assess
the rate and causes of self-discharge in this province, so this study is aimed to
fill this gap. METHODS AND MATERIALS: This descriptive and cross-sectional study
was carried out in 6 months period, from 23 July 2010 till 20 January 2011 in all
public hospitals of Mazandaran province. A form was set out for data collection
and those patients willing to self-discharge were asked to participate in the
study. Patients' demographic information was filled using their medical record
and by the help of department personnel. Furthermore, the form was completed by
parents for patients over 18 year-old or by the help of first-rank relative for
those having psychiatric disorders or anybody who wasn't able to complete the
form. In order to identify the causes of self-discharge, 18 variables were
determined which were categorized in three general items and five main groups.
Data were entered into the SPSS15 and were analyzed using descriptive statistics
indices. RESULTS: According to the results, 94441 were discharged from the
university hospitals which 7967 patients (8.4 %) of them were self-discharged
during the 6 month study period. Regarding admission type, 269 (3.3 %), (54.5 %)
were admitted into the hospital by pre-determined appointment and as usual
patients, respectively, and the rest were admitted by emergency department. Also,
31.4%(2504) were hospitalized in surgery ward, 63% (5026) in medical ward, 4.6%
(374) in intensive care unit (ICU) and the rest were hospitalized in the
psychiatric ward. The most important reasons for self-discharge were related to:
1-factors affecting patient illness (54.3%), 2-environmental issues as well as
patients' accompanying (37.6%) and 3-managerial and medical reasons(7.9%),
respectively. CONCLUSION: Our study showed the same results for Discharge against
medical advice rate as the others. From the view point of treatment management,
its causes should be considered and practices should be done to improve the
conditions. Meanwhile, the current self-discharge form doesn't reflect the causes
of the problem and it should be revised.
PMID- 25126019
TI - Effects of lipoic Acid on acrylamide induced testicular damage.
AB - INTRODUCTION: Acrylamide is very toxic to various organs and associated with
significant increase of oxidative stress and depletion of antioxidants. Alpha
lipoic acid enhances cellular antioxidant defense capacity, thereby protecting
cells from oxidative stress. AIM OF THE STUDY: This study aimed to evaluate the
protective role of alpha-lipoic acid on the oxidative damage induced by
acrylamide in testicular and epididymal tissues. MATERIAL AND METHODS: Forty
adult male rats were divided into four groups (10 rats each). Control group;
acrylamide treated group administered acrylamide 0.05% (w/v) in drinking water
for 21 days; alpha-lipoic acid group received basal diet supplemented with 1%
alpha-lipoic acid and forth group was exposed to acrylamide and treated with
alpha-lipoic acid at the same doses and treatment regimen mentioned before.
RESULTS: The administration of acrylamide resulted in significant elevation in
testicular and epididymal malondialdehyde level (MDA) and significant reduction
in the level of reduced glutathione (GSH) and the activities of glutathione-S
transferase (GST), glutathione peroxidase (GPX) and glutathione reductase (GR).
Also, acrylamide significantly reduced serum total testosterone and progesterone
but increased estradiol (E2) levels. Treatment with alpha-lipoic acid prior to
acrylamide induced protective effects and attenuated these biochemical changes.
CONCLUSION: Alpha-lipoic acid has been shown to possess antioxidant properties
offering promising efficacy against oxidative stress induced by acrylamide
administration.
PMID- 25126020
TI - Correlates of hypertension among adult men and women in kosovo.
AB - AIM: We aimed to assess the independent socioeconomic, behavioral and
psychosocial correlates of hypertension among the adult population of Kosovo.
METHODS: This was a cross-sectional study carried out in Pristina in 2012-2013
which included a large representative sample of 1793 consecutive primary health
care users aged >=35 years (mean age: 51.2+/-6.7 years; 52.5% women; overall
response: 95%). Systolic and diastolic blood pressure was measured, whereas
demographic and socioeconomic characteristics (age, sex, marital status, place of
residence, education, employment status and income), lifestyle factors (smoking,
alcohol intake, physical exercise and dietary fat intake) and psychosocial
factors (hostility and reaction to transition) were assessed through a structured
questionnaire. Multivariable-adjusted binary logistic regression was used to
assess the independent "predictors" of hypertension. RESULTS: Upon simultaneous
adjustment in a backward stepwise elimination procedure for all socioeconomic
characteristics, lifestyle factors and psychosocial factors, significant positive
correlates of hypertension were older age (OR=1.03, 95%CI=1.01-1.05), male gender
(OR=1.41, 95%CI=1.19-1.58), a lower educational attainment (OR=1.36, 95%CI=1.08
1.67), smoking (OR=1.53, 95%CI=1.28-2.16), physical inactivity (OR=1.98,
95%CI=1.46-2.74) and hostility (OR=1.42, 95%CI=1.17-2.08). CONCLUSIONS: Findings
from this study conducted in transitional Kosovo are generally in line with
previous reports from the Western Balkan countries and beyond. Decision-makers
and policymakers should be aware of the rising trend and socioeconomic,
behavioral and psychosocial determinants of hypertension in post-war Kosovo.
PMID- 25126021
TI - Bidirectional Associations Among Sensitive Parenting, Language Development, and
Social Competence.
AB - Rapid changes in language skills and social competence, both of which are linked
to sensitive parenting, characterize early childhood. The present study examines
bidirectional associations among mothers' sensitive parenting and children's
language skills and social competence from 24 to 36 months in a community sample
of 174 families. In addition, this study examines how these developmental
pathways vary by child sex. Findings indicate stability across time in sensitive
parenting, expressive language skills, and social competence, as well as positive
main effects of sensitive parenting on expressive and receptive language skills
for girls and boys. We find mixed evidence over time of reciprocal links between
social competence and sensitive parenting. Further, boys' receptive language
skills at 24 months uniquely contribute to increases in mothers' observed
sensitive parenting from 24 to 36 months. These findings highlight the utility of
applying transactional frameworks to the study of sex-based differences in early
developmental processes.
PMID- 25126022
TI - What are we 'tweeting' about obesity? Mapping tweets with Topic Modeling and
Geographic Information System.
AB - Public health related tweets are difficult to identify in large conversational
datasets like Twitter.com. Even more challenging is the visualization and
analyses of the spatial patterns encoded in tweets. This study has the following
objectives: How can topic modeling be used to identify relevant public health
topics such as obesity on Twitter.com? What are the common obesity related
themes? What is the spatial pattern of the themes? What are the research
challenges of using large conversational datasets from social networking sites?
Obesity is chosen as a test theme to demonstrate the effectiveness of topic
modeling using Latent Dirichlet Allocation (LDA) and spatial analysis using
Geographic Information System (GIS). The dataset is constructed from tweets
(originating from the United States) extracted from Twitter.com on obesity
related queries. Examples of such queries are 'food deserts', 'fast food', and
'childhood obesity'. The tweets are also georeferenced and time stamped. Three
cohesive and meaningful themes such as 'childhood obesity and schools', 'obesity
prevention', and 'obesity and food habits' are extracted from the LDA model. The
GIS analysis of the extracted themes show distinct spatial pattern between rural
and urban areas, northern and southern states, and between coasts and inland
states. Further, relating the themes with ancillary datasets such as US census
and locations of fast food restaurants based upon the location of the tweets in a
GIS environment opened new avenues for spatial analyses and mapping. Therefore
the techniques used in this study provide a possible toolset for computational
social scientists in general and health researchers in specific to better
understand health problems from large conversational datasets.
PMID- 25126023
TI - Surface Mediated Structures: Stabilization of Metastable Polymorphs on the
Example of Paracetamol.
AB - The preparation of typically thermodynamically unstable polymorphic structures is
a challenge. However, solid surfaces are well established aids for the formation
and stabilization of polymorphic structures within, for instance, organic
electronics. In this study, we report the stabilization of a pharmaceutically
relevant substance via a solid surface at ambient conditions. Form III of
paracetamol, which is typically unstable in the bulk at standard conditions, can
be stabilized with a model silica surface by a standard spin coating procedure
followed by rapid heat treatment. Such a preparation technique allows the use of
atomic force microscopy and grazing incidence X-ray diffraction measurements
revealing detailed information on the morphology and structure of the polymorph.
Furthermore, the results exhibit that this polymorph is stable over a long period
of time revealing surface mediated stabilization. These findings demonstrate a
novel approach to provide thermodynamic stability when applied to similar
molecules with specific applications.
PMID- 25126025
TI - Joy in the practice of sleep medicine.
PMID- 25126026
TI - The case of simultaneous submission: "Flying too close to the sun".
PMID- 25126024
TI - Prevalence and correlates of HIV risk among adolescents and young adults
reporting drug use: Data from an urban Emergency Department in the U.S.
AB - Adolescents and young adults who use substances are at particularly high risk for
contracting Human Immunodeficiency Virus (HIV). The Emergency Department (ED) is
a critical location for HIV prevention for at-risk youth. To inform future
interventions in the ED, this study identifies correlates of HIV risk behaviors
among substance using youth seeking ED care. Among 600 14-24-year-olds with past
6-month drug use, bivariate correlates of HIV risk included: older age, female
gender, depressive symptoms, alcohol use, marijuana use, other drug use, and
dating, peer, and community violence. Regression analyses indicated that older
age, marijuana use, and dating violence were positively related to HIV risk.
Results suggest HIV prevention efforts for youth in the urban ED should address
marijuana use and dating violence as well as sexual risk behaviors.
PMID- 25126028
TI - Resistant hypertension and untreated severe sleep apnea: slowly gaining insight.
PMID- 25126027
TI - Association of severe obstructive sleep apnea and elevated blood pressure despite
antihypertensive medication use.
AB - RATIONALE: We hypothesized that untreated severe obstructive sleep apnea (OSA) is
associated with elevated ambulatory blood pressure (BP) in subjects with high
cardiovascular disease (CVD) risk despite medical management. METHODS: Data from
the baseline examination of the Heart Biomarker Evaluation in Apnea Treatment
(HeartBEAT) study, a 4-site randomized controlled trial were analyzed.
Individuals with moderate-severe OSA (apnea hypopnea index, AHI = 15-50) and
cardiovascular risk were recruited from cardiology practices. Those with
hypertension were included. Intensive antihypertensive regimen (IAR) was defined
as >= 3 antihypertensives including a diuretic. Definitions were: controlled BP
(BP < 130/80), uncontrolled elevated BP (BP >= 130/80 not on IAR) and resistant
elevated BP (BP >= 130/80 mm Hg despite IAR). Associations of untreated severe
OSA (AHI >= 30) and uncontrolled and resistant elevated BP were evaluated using
logistic regression analyses adjusted for age, sex, race, body mass index,
smoking status, diabetes, and CVD. RESULTS: Among the 284 participants (mean age
63.1 +/- 7.2 years, 23.6% with severe OSA), 61.6% had controlled BP, 28.5% had
uncontrolled elevated BP, and 9.9% had resistant elevated BP. Among participants
prescribed IAR, resistant elevated BP was more prevalent in those with severe
compared to moderate OSA (58.3% vs. 28.6%, p = 0.01). Participants with severe
OSA had a 4-fold higher adjusted odds of resistant elevated BP (OR 4.1, 95% CI:
1.7-10.2), a finding not reproduced in the absence of IAR use. CONCLUSIONS: Among
patients with increased cardiovascular risk and moderate to severe OSA, untreated
severe compared to moderate OSA was associated with elevated BP despite IAR
suggesting untreated severe OSA contributes to poor BP control despite aggressive
medication use. COMMENTARY: A commentary on this article appears in this issue on
page 845.
PMID- 25126030
TI - Effect of opioids on sleep and breathing in chronic pain patients.
PMID- 25126029
TI - Sleep disordered breathing and chronic respiratory failure in patients with
chronic pain on long term opioid therapy.
AB - STUDY OBJECTIVES: The use of opioid medication for chronic pain has been
increasing. The main aim of this study was to assess how many patients on opioids
for chronic pain had sleep disordered breathing (SDB) and the type of SDB. The
impact of these medications on daytime arterial blood gas (ABG) measurements and
psychomotor vigilance was also studied. METHODS: Twenty-four patients (aged 18-75
years) on long-term opioids were prospectively recruited. Patients underwent home
polysomnogram (PSG), psychomotor vigilance testing (PVT), and awake daytime ABG.
Overnight PSG findings were compared to those of patients matched for age, sex,
and BMI referred to our sleep service for evaluation of SDB. PVT results in the
patient cohort were compared to PVT in healthy controls. RESULTS: Forty-six
percent of opioid patients had severe SDB as defined by an apnea hypopnea index
(AHI) > 30/h. The severity of SDB was similar in opioid-treated pain clinic
patients and sleep clinic patients (mean +/- SD AHI: Opioid-treated patients 32.7
+/- 25.6; Sleep Study comparator group 28.9 +/- 24.6, p = 0.6). Opioid patients
had a higher frequency of central apneas and a lower arousal index (CAI: 3.9 +/-
8.3 vs. 0.3 +/- 0.5 events/h; p = 0.004, AI 8.0 +/- 4.1 vs. 20.1 +/- 13.8, p <
0.001). Pain clinic patients had impaired gas exchange during sleep and
wakefulness. Nine of 20 (45%) had daytime hypercapnia, indicating a surprising
number were in chronic respiratory failure. Morphine equivalent doses correlated
with the severity of SDB. PVT was impaired when compared to a healthy PVT
comparator group (RT: Opioid-treated patients 0.43 +/- 0.27: Healthy PVT
comparator group 0.28 +/- 0.03 sec; p < 0.001). CONCLUSIONS: Patients on long
term opioids frequently have severe SDB, which in part is central in origin. PVT
was markedly impaired. Half of the patients studied have evidence of chronic
ventilatory failure. COMMENTARY: A commentary on this article appears in this
issue on page 853
PMID- 25126031
TI - A novel adaptive servoventilation (ASVAuto) for the treatment of central sleep
apnea associated with chronic use of opioids.
AB - STUDY OBJECTIVES: To compare the efficacy and patient comfort of a new mode of
minute ventilation-targeted adaptive servoventilation (ASVAuto) with auto
titrating expiratory positive airway pressure (EPAP) versus bilevel with back-up
respiratory rate (bilevel-ST) in patients with central sleep apnea (CSA)
associated with chronic use of opioid medications. METHODS: Prospective,
randomized, crossover polysomnography (PSG) study. Eighteen consecutive patients
(age >= 18 years) who had been receiving opioid therapy (>= 6 months), and had
sleep disordered breathing with CSA (central apnea index [CAI] >= 5) diagnosed
during an overnight sleep study or positive airway pressure (PAP) titration were
enrolled to undergo 2 PSG studies-one with ASVAuto and one with bilevel-ST.
Patients completed 2 questionnaires after each PSG; Morning After Patient
Satisfaction Questionnaire and PAP Comfort Questionnaire. RESULTS: Patients had a
mean age of 52.9 +/- 15.3 years. PSG prior to randomization showed an apnea
hypopnea index (AHI) of 50.3 +/- 22.2 and CAI of 13.0 +/- 18.7. Titration with
ASVAuto versus bilevel-ST showed that there were significant differences with
respect to AHI and CAI. The AHI and CAI were significantly lower on ASVAuto than
bilevel-ST (2.5 +/- 3.5 versus 16.3 +/- 20.9 [p = 0.0005], and 0.4 +/- 0.8 versus
9.4 +/- 18.8 [p = 0.0002], respectively). Respiratory parameters were normalized
in 83.3% of patients on ASVAuto versus 33.3% on bilevel-ST. Patients felt more
awake and alert on ASVAuto than bilevel-ST based on scores from Morning After
Patient Satisfaction Questionnaire (p = 0.0337). CONCLUSIONS: The ASVAuto was
significantly more effective than bilevel-ST for the treatment of CSA associated
with chronic opioid use.
PMID- 25126032
TI - Assessment of a neck-based treatment and monitoring device for positional
obstructive sleep apnea.
AB - STUDY OBJECTIVES: A majority of patients diagnosed with obstructive sleep apnea
are position dependent whereby they are at least twice as severe when sleeping
supine (POSA). This study evaluated the accuracy and efficacy of a neck-worn
device designed to limit supine sleep. The study included nightly measurements of
snoring, sleep/wake, time supine, and the frequency and duration of feedback to
monitor compliance. METHODS: Thirty patients between ages 18 and 75 years, BMI <=
35 with an overall apnea-hypopnea index (AHI) >= 5 and an overall AHI >= 1.5
times the non-supine AHI, and an Epworth score >= 5 were prospectively studied.
Subjective reports and polysomnography were used to assess efficacy resulting
from 4 weeks of in-home supine-avoidance therapy and to measure device accuracy.
From 363 polysomnography reports, 209 provided sufficient positional data to
estimate one site's prevalence of positional OSA. RESULTS: In 83% of participants
exhibiting > 50% reduction in overall AHI, the mean and median reductions were
69% and 79%. Significant reductions in the overall and supine AHI, apnea index,
percent time SpO2 < 90%, and snoring contributed to significant improvements in
stage N1 and N2 sleep, reductions in cortical arousals and awakenings, and
improved depression scores. Supine position was under-detected by > 5% in 3% of
cases. Sleep efficiency by neck actigraphy was within 10% of polysomnography in
87% of the studies when position feedback was delivered. The prevalence of POSA
was consistently > 70% when the overall AHI was < 60. CONCLUSIONS: The neck
position therapy device is accurate and effective in restricting supine sleep,
improving AHI, sleep architecture and continuity, and monitoring treatment
outcomes.
PMID- 25126033
TI - Complete blood count alterations after six months of continuous positive airway
pressure treatment in patients with severe obstructive sleep apnea.
AB - STUDY OBJECTIVES: The cardiovascular complications caused by obstructive sleep
apnea (OSA) decrease after continuous positive airway pressure treatment (CPAP).
Mean platelet volume (MPV), platelet distribution width (PDW), and red cell
distribution width (RDW) are newly recognized tools for assessing cardiovascular
risk. METHODS: From a selection of patients with symptoms of nocturnal snoring
and/or excessive daytime sleepiness, 36 males with an apnea-hypopnea index (AHI)
> 30/h and 22 age-matched normal male controls with AHI < 5/h were included.
Patients with OSA underwent another night of CPAP titration, and 11 patients were
excluded at the 6-month evaluation due to poor compliance with the home CPAP
therapy. Complete blood count parameters of compliant patients and the control
group were evaluated. RESULTS: Compared to controls, MPV values were
significantly higher (p = 0.025) in OSA patients, but no significant differences
in PDW or RDW were found (p > 0.05). Six months of CPAP therapy resulted in
significantly lower MPV values but increased values of PDW and RDW in patients
with severe OSA (p = 0.001, p = 0.007, p = 0.001, respectively). CONCLUSION: Our
data suggest that complete blood count parameters in OSA patients such as MPV,
PDW and RDW change significantly after CPAP therapy.
PMID- 25126034
TI - Home-based diagnosis of obstructive sleep apnea in an urban population.
AB - STUDY OBJECTIVES: Home-based diagnosis of obstructive sleep apnea (OSA) with
portable monitoring (PM) is increasingly utilized, but remains understudied in
underserved and minority populations. We tested the feasibility of home PM in an
urban population at risk for OSA compared to in-laboratory polysomnography (PSG)
and examined patient preference with respect to home PM versus PSG. METHODS:
Randomized crossover study of home PM (WatchPAT200) and in-laboratory
simultaneous PSG and PM in 75 urban African Americans with high pre-test
probability of OSA, identified with the Berlin questionnaire. RESULTS: Fifty
seven of 75 participants were women, average age 45 +/- 11 years (mean +/- SD),
35% with <= high school education, and 76% with annual household income <
$50,000. Technical failure rates were 5.3% for home vs. 3.1% for in-laboratory
PM. There was good agreement between apnea hypopnea index on PSG; AHIPSG and AHI
on home PM (mean +/- 2 SD of the differences = 0.64 +/- 46.5 and intraclass
correlation coefficient; ICC = 0.73). The areas under the curve for the receiver
operator characteristic curves for home PM were 0.90 for AHIPSG >= 5, 0.95 for
AHIPSG >= 10, and 0.92 for AHIPSG >= 15. 62/75 (82%) participants preferred home
over in-laboratory testing. CONCLUSIONS: Home PM for diagnosis of OSA in a high
risk urban population is feasible, accurate, and preferred by patients. As home
PM may improve access to care, the cost-effectiveness of this diagnostic strategy
for OSA should be examined in underserved urban and rural populations. CLINICAL
TRIALS REGISTRATION: ClinicalTrials.gov, identifier: NCT01997723.
PMID- 25126035
TI - The efficacy of a chinstrap in treating sleep disordered breathing and snoring.
AB - STUDY OBJECTIVES: A previously published case report suggested that a chinstrap
alone might improve obstructive sleep apnea (OSA). We conducted this study to
determine whether a chinstrap was a feasible alternative to continuous positive
airway pressure (CPAP) in patients with OSA. METHODS: 26 adult patients with OSA
(apnea-hypopnea index [AHI] > 5/h on diagnostic polysomnogram [PSG]) underwent a
modified split-night PSG, using only a chinstrap for the first 2 hours of sleep,
followed by CPAP titration for the remainder of the night. Improvements in AHI,
arterial oxygen saturation (SpO2), and snoring with chinstrap use were compared
to results with optimal CPAP pressures. RESULTS: There was no significant
difference between the diagnostic PSG and the chinstrap portion of the split
night PSG in the following parameters: general AHI (median [IQR] 16.0/h [9.7
26.0] vs. 25.9/h [10.7-42.7]), SpO2 nadir (84.0% [80.5-87.5] vs. 87.0 [84.0
88.5]), AHI in REM sleep (26.7/h [16.8-43.7] vs. 42.4/h [21.3-57.7]), AHI in
supine sleep (24.9/h [11.9-51.5] vs. 29.8/h [11.7-55.5]), snoring index (253.2/h
[147.5-353.1] vs. 180.0/h [9.8-393.3]) or subjective snoring scale (3.0 [0.8-3.0]
vs. 2.5 [0.4-3.0]). The AHI and SpO2 nadir in the 13 patients with mild OSA also
did not improve with chinstrap use (9.6/h [8.1-12.2] vs. 10.6/h [6.8-35.4] and
87.0% [83.0-90.0] vs. 88.0% [87.0-89.0]). All these parameters showed significant
improvement with optimal CPAP titration (p < 0.05). CONCLUSIONS: A chinstrap
alone is not an effective treatment for OSA. It does not improve sleep disordered
breathing, even in mild OSA, nor does it improve the AHI in REM sleep or supine
sleep. It is also ineffective in improving snoring.
PMID- 25126036
TI - Effect of sensory stimuli on restless legs syndrome: a randomized crossover
study.
AB - STUDY OBJECTIVE: A variety of sensory stimuli relieve restless legs syndrome
symptoms. Because systematic evaluations of sensory stimulation in restless legs
syndrome are largely lacking, we performed a randomized crossover study to
evaluate the effect of external sensory stimulation on restless legs syndrome
symptoms. METHODS: Eighteen patients underwent 3 consecutive suggestive
immobilization tests with the order of the following 3 conditions randomly
assigned: no electrical stimulation (condition 1), tactile and proprioceptive
sensory stimulation (condition 2), and tactile sensory stimulation only
(condition 3). Restless legs syndrome symptoms were quantified by visual analog
scales, and periodic leg movements during wake were measured. RESULTS: Baseline
visual analogue scale score was 4.5 (range 0-60) in condition 1, 10.5 (range 0
96) in condition 2, and 8.5 in condition 3 (p = 0.21). There was a tendency
towards a higher maximum visual analogue scale score and visual analogue scale
score at the end of the suggested immobilization test in the conditions with
tactile sensory stimulation, though not significant (p = 0.74 and p = 0.29,
respectively). Fifteen patients suffered from periodic leg movements during wake.
Median indices were 18 (range 0-145) in condition 1, 26 (range 0-190) in
condition 2, and 49 (range 0-228) in condition 3 (p = 0.76). CONCLUSIONS: We
found a tendency towards less leg discomfort in the conditions in which an
external sensory input was applied. This potential benefit of sensory stimuli on
restless legs syndrome severity merits further investigation as this could open
new ways towards a better pathophysiological understanding and non
pharmacological treatments.
PMID- 25126037
TI - Drug testing in children with excessive daytime sleepiness during multiple sleep
latency testing.
AB - STUDY OBJECTIVE: To determine the incidence of positive drug screens in children
undergoing a multiple sleep latency test (MSLT) for evaluation of excessive
daytime sleepiness (EDS). METHODS: A retrospective analysis was performed in
children evaluated at the Boston Children's Hospital Sleep Center between 1998
and 2013 who underwent MSLT for EDS with a concurrent urine and/or serum drug
screen. RESULTS: A total of 210 MSLTs were accompanied by drug testing. Children
were 12.7 +/- 3.7 years old (mean +/- SD), 43% were female, and 24% had
narcolepsy. Positive tests were obtained in 32% for caffeine, 5% for prescription
medications, and 4% for over-the-counter drugs. No drugs of abuse were
identified. Children testing positive for caffeine were older (13.8 +/- 3.5 vs.
12.4 +/- 3.7) and more likely female (59% vs. 36%), but did not differ in MSLT or
overnight polysomnographic parameters compared to children without caffeine
detected. Overall, only 14% had specific documentation regarding caffeine intake,
though 90% were referred from a sleep clinic. Of the children testing positive
for caffeine, 5% acknowledged use, 3% denied use, and 92% did not have a
documented caffeine intake history during their sleep clinic visit. CONCLUSIONS:
Routine drug testing for drugs of abuse during an MSLT for EDS yielded no
positive results over a 15-year period, indicating that this routine practice is
unnecessary in our pediatric population without specific concerns. However,
objective evidence for caffeine exposure was found in 32% of tested children
undergoing an MSLT. Sleep physicians rarely documented the caffeine intake
history during clinic visits for EDS.
PMID- 25126038
TI - Do respiratory cycle-related EEG changes or arousals from sleep predict
neurobehavioral deficits and response to adenotonsillectomy in children?
AB - STUDY OBJECTIVES: Pediatric obstructive sleep apnea (OSA) is associated with
hyperactive behavior, cognitive deficits, psychiatric morbidity, and sleepiness,
but objective polysomnographic measures of OSA presence or severity among
children scheduled for adenotonsillectomy have not explained why. To assess
whether sleep fragmentation might explain neurobehavioral outcomes, we
prospectively assessed the predictive value of standard arousals and also
respiratory cycle-related EEG changes (RCREC), thought to reflect inspiratory
microarousals. METHODS: Washtenaw County Adenotonsillectomy Cohort II
participants included children (ages 3-12 years) scheduled for
adenotonsillectomy, for any clinical indication. At enrollment and again 7.2 +/-
0.9 (SD) months later, children had polysomnography, a multiple sleep latency
test, parent-completed behavioral rating scales, cognitive testing, and
psychiatric evaluation. The RCREC were computed as previously described for
delta, theta, alpha, sigma, and beta EEG frequency bands. RESULTS: Participants
included 133 children, 109 with OSA (apnea-hypopnea index [AHI] >= 1.5, mean 8.3
+/- 10.6) and 24 without OSA (AHI 0.9 +/- 0.3). At baseline, the arousal index
and RCREC showed no consistent, significant associations with neurobehavioral
morbidities, among all subjects or the 109 with OSA. At follow-up, the arousal
index, RCREC, and neurobehavioral measures all tended to improve, but neither
baseline measure of sleep fragmentation effectively predicted outcomes (all p >
0.05, with only scattered exceptions, among all subjects or those with OSA).
CONCLUSION: Sleep fragmentation, as reflected by standard arousals or by RCREC,
appears unlikely to explain neurobehavioral morbidity among children who undergo
adenotonsillectomy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, ID:
NCT00233194.
PMID- 25126039
TI - Feasibility of comprehensive, unattended ambulatory polysomnography in school
aged children.
AB - STUDY OBJECTIVES: Although unattended ambulatory polysomnography (PSG) is
frequently performed in adults, few studies have been performed in children. The
objective of this study was to evaluate the feasibility of comprehensive,
ambulatory PSG, including electroencephalography, in school-aged children in the
home environment. METHODS: A total of 201 children, born premature with birth
weights of 500-1,250 grams, currently aged 5-12 years and living in Canada and
Australia, underwent unattended ambulatory PSG. RESULTS: PSG was initially
technically satisfactory in 183 (91%) cases. Fourteen studies were satisfactory
when repeated, resulting in an overall satisfactory rate of 197 (98%). Artifact
free signals were obtained for >= 75% of recording time in more than 92% of
subjects, with the exception of nasal pressure, which was satisfactory for >= 75%
of recording time in only 67% of subjects. However, thermistry signals were
satisfactory for >= 75% of recording time in 92% of subjects, and some measure of
airflow was present for >= 75% of recording time in 96% of subjects. Children
slept very well, with a long total sleep time (534 +/- 73 [mean +/- SD] minutes),
high sleep efficiency (92% +/- 5%), and low arousal index (9 +/- 3/h). Parents
and children reported a high rate of satisfaction with the study. CONCLUSIONS:
This large, international study has shown that comprehensive, unattended,
ambulatory PSG is feasible, technically adequate and well-tolerated in school
aged children when performed under research conditions. Further studies regarding
the cost efficacy of this approach, and generalizability of the findings to a
clinical population, are warranted.
PMID- 25126041
TI - Adult NREM parasomnia associated with lancinating throat pain.
AB - We report the case of a 30-year-old woman presenting with dangerous nocturnal
NREM episodes with the clinical feature of lancinating throat pain. We
hypothesize that the pain may have represented sensory hallucination analogous to
commonly recognized visual images associated with NREM parasomnias. This case is
also unusual for probable psychological triggers that could play a role in the
pathogenesis of the disease, as evidenced by successful psychotherapy.
PMID- 25126040
TI - Assessing and predicting the likelihood of interventions during routine annual
follow-up visits for management of obstructive sleep.
AB - STUDY OBJECTIVES: Patients with obstructive sleep apnea (OSA) on established
positive airway pressure (PAP) treatment are often advised routine annual follow
up visits to assess ongoing effectiveness and address problems associated with
therapy. This study evaluates the clinical utility of annual face-to-face follow
up visits. DESIGN: We performed a retrospective chart review of OSA patients on
PAP who had completed a routine annual follow-up visit. Demographics,
polysomnography, PAP compliance, Epworth Sleepiness Scale (ESS), subjective
complaints (efficacy and interface issues, equipment malfunction, prescription
renewal), objective findings (efficacy or leak issues, equipment problems), and
visit-specific interventions were recorded. We determined relationships between
patient provided information and likelihood of therapeutic versus administrative
interventions. SETTING: Academic sleep center. MEASUREMENTS AND RESULTS: Among
716 patients who met study criteria, we abstracted data on 180 randomly selected
patients. On multivariate analyses, only subjective complaints or objective
findings by providers were associated with a therapeutic intervention (p <
0.0001). Though most patients (55 of 63 patients, 87.3%) who required therapeutic
interventions had objective findings, without subjective complaints, the odds of
such findings were only 0.12 (95% CI = 0.06-0.24, p < 0.0001). Without subjective
complaints, the likelihood of a therapeutic intervention was 0.07 (95% CI = 0.03
0.15, p < 0.001). CONCLUSION: Our data suggests that in the absence of a
subjective complaint, an annual follow-up is more likely to require
administrative rather than face-to-face clinical intervention. Designing a clinic
model to account for this might reduce resource utilization. However, the value
and optimal timing of "routine" annual follow-up visits requires further
evaluation.
PMID- 25126043
TI - Cognitive benefits of computer games for older adults.
AB - The purpose of this paper is to develop a basis for the hypothesis that digital
action games may produce cognitive benefits for older adults. First, a discussion
of the relationship between cognitive and physical health shows the increasing
weight given to the role of declines in cognition in the development of
dependency in older adult population studies. Second, evidence that cognitive
training produces 'far transfer' in elders is presented. The key issue is that
one approach, known as extended practice training, has been successful in
producing far transfer to memory and other processes. Its principles, which are
consistent with those associated with positive brain plasticity effects, are
identified. Those principles are then related to the mechanics of digital action
games, which also have the important added feature of producing the experiences
of presence, engagement, and flow, the subjective elements of game play that are
likely to sustain interest and emotional investment in the skills practiced so
that the play produces cognitive benefits. The specific cognitive abilities
proposed to be improved by different types of game genres are outlined, and
recent developments in game and interface design that may affect the willingness
of older adults to play are described.
PMID- 25126042
TI - Sleep-related violence and sexual behavior in sleep: a systematic review of
medical-legal case reports.
AB - OBJECTIVE: To review systematically medical-legal cases of sleep-related violence
(SRV) and sexual behavior in sleep (SBS). SEARCH METHODS: We searched Pubmed and
PsychINFO (from 1980 to 2012) with pre-specified terms. We also searched
reference lists of relevant articles. SELECTION CRITERIA: Case reports in which a
sleep disorder was purported as the defense during a criminal trial and in which
information about the forensic evaluation of the defendant was provided. DATA
EXTRACTION AND ANALYSIS: Information about legal issues, defendant and victim
characteristics, circumstantial factors, and forensic evaluation was extracted
from each case. A qualitative-comparative assessment of cases was performed.
RESULTS: Eighteen cases (9 SRV and 9 SBS) were included. The charge was murder or
attempted murder in all SRV cases, while in SBS cases the charge ranged from
sexual touching to rape. The defense was based on sleepwalking in 11 of 18 cases.
The trial outcome was in favor of the defendant in 14 of 18 cases. Defendants
were relatively young males in all cases. Victims were usually adult relatives of
the defendants in SRV cases and unrelated young girls or adolescents in SBS
cases. In most cases the criminal events occurred 1-2 hours after the defendant's
sleep onset, and both proximity and other potential triggering factors were
reported. The forensic evaluations widely differed from case to case. CONCLUSION:
SRV and SBS medical-legal cases did not show apparent differences, except for the
severity of the charges and the victim characteristics. An international
multidisciplinary consensus for the forensic evaluation of SRV and SBS should be
developed as an urgent priority.
PMID- 25126044
TI - The regulation of coenzyme q biosynthesis in eukaryotic cells: all that yeast can
tell us.
AB - Coenzyme Q (CoQ) is a mitochondrial lipid, which functions mainly as an electron
carrier from complex I or II to complex III at the mitochondrial inner membrane,
and also as antioxidant in cell membranes. CoQ is needed as electron acceptor in
beta-oxidation of fatty acids and pyridine nucleotide biosynthesis, and it is
responsible for opening the mitochondrial permeability transition pore. The yeast
model has been very useful to analyze the synthesis of CoQ, and therefore, most
of the knowledge about its regulation was obtained from the Saccharomyces
cerevisiae model. CoQ biosynthesis is regulated to support 2 processes: the
bioenergetic metabolism and the antioxidant defense. Alterations of the carbon
source in yeast, or in nutrient availability in yeasts or mammalian cells,
upregulate genes encoding proteins involved in CoQ synthesis. Oxidative stress,
generated by chemical or physical agents or by serum deprivation, modifies
specifically the expression of some COQ genes by means of stress transcription
factors such as Msn2/4p, Yap1p or Hsf1p. In general, the induction of COQ gene
expression produced by metabolic changes or stress is modulated downstream by
other regulatory mechanisms such as the protein import to mitochondria, the
assembly of a multi-enzymatic complex composed by Coq proteins and also the
existence of a phosphorylation cycle that regulates the last steps of CoQ
biosynthesis. The CoQ biosynthetic complex assembly starts with the production of
a nucleating lipid such as HHB by the action of the Coq2 protein. Then, the Coq4
protein recognizes the precursor HHB acting as the nucleus of the complex. The
activity of Coq8p, probably as kinase, allows the formation of an initial pre
complex containing all Coq proteins with the exception of Coq7p. This pre-complex
leads to the synthesis of 5-demethoxy-Q6 (DMQ6), the Coq7p substrate. When de
novo CoQ biosynthesis is required, Coq7p becomes dephosphorylated by the action
of Ptc7p increasing the synthesis rate of CoQ6. This critical model is needed for
a better understanding of CoQ biosynthesis. Taking into account that patients
with CoQ10 deficiency maintain to some extent the machinery to synthesize CoQ,
new promising strategies for the treatment of CoQ10 deficiency will require a
better understanding of the regulation of CoQ biosynthesis in the future.
PMID- 25126046
TI - Clinical presentations of coenzyme q10 deficiency syndrome.
AB - Coenzyme Q10 (CoQ10) deficiency is a clinically and genetically heterogeneous
syndrome which has been associated with 5 major clinical phenotypes: (1)
encephalomyopathy, (2) severe infantile multisystemic disease, (3) nephropathy,
(4) cerebellar ataxia, and (5) isolated myopathy. Of these phenotypes, cerebellar
ataxia and syndromic or isolated nephrotic syndrome are the most common. CoQ10
deficiency predominantly presents in childhood. To date, causative mutations have
been identified in a small proportion of patients, making it difficult to
identify a phenotype-genotype correlation. Identification of CoQ10 deficiency is
important because the disease, in particular muscle symptoms and nephropathy,
frequently responds to CoQ10 supplementation.
PMID- 25126047
TI - Biochemical diagnosis of coenzyme q10 deficiency.
AB - Coenzyme Q10 (CoQ10) deficiency appears to have a particularly heterogeneous
clinical presentation. However, there appear to be 5 recognisable clinical
phenotypes: encephalomyopathy, severe infantile multisystemic disease,
nephropathy, cerebellar ataxia, and isolated myopathy. However, although useful,
clinical symptoms alone are insufficient for the definitive diagnosis of CoQ10
deficiency which relies upon biochemical assessment of tissue CoQ10 status. In
this article, we review the biochemical methods used in the diagnosis of human
CoQ10 deficiency and indicate the most appropriate tissues for this evaluation.
PMID- 25126045
TI - Coenzyme q and the respiratory chain: coenzyme q pool and mitochondrial
supercomplexes.
AB - Two alternative models of organization of the mitochondrial electron transport
chain (mETC) have been alternatively favored or questioned by the accumulation
evidences of different sources, the solid model or the random collision model.
Both agree in the number of respiratory complexes (I-IV) that participate in the
mETC, but while the random collision model proposes that Complexes I-IV do not
interact physically and that electrons are transferred between them by coenzyme Q
and cytochrome c, the solid model proposes that all complexes super-assemble in
the so-called respirasome. Recently, the plasticity model has been developed to
incorporate the solid and the random collision model as extreme situations of a
dynamic organization, allowing super-assembly free movement of the respiratory
complexes. In this review, we evaluate the supporting evidences of each model and
the implications of the super-assembly in the physiological role of coenzyme Q.
PMID- 25126048
TI - Genetics of coenzyme q10 deficiency.
AB - Coenzyme Q10 (CoQ10) is an essential component of eukaryotic cells and is
involved in crucial biochemical reactions such as the production of ATP in the
mitochondrial respiratory chain, the biosynthesis of pyrimidines, and the
modulation of apoptosis. CoQ10 requires at least 13 genes for its biosynthesis.
Mutations in these genes cause primary CoQ10 deficiency, a clinically and
genetically heterogeneous disorder. To date mutations in 8 genes (PDSS1, PDSS2,
COQ2, COQ4, COQ6, ADCK3, ADCK4, and COQ9) have been associated with CoQ10
deficiency presenting with a wide variety of clinical manifestations. Onset can
be at virtually any age, although pediatric forms are more common. Symptoms
include those typical of respiratory chain disorders (encephalomyopathy, ataxia,
lactic acidosis, deafness, retinitis pigmentosa, hypertrophic cardiomyopathy),
but some (such as steroid-resistant nephrotic syndrome) are peculiar to this
condition. The molecular bases of the clinical diversity of this condition are
still unknown. It is of critical importance that physicians promptly recognize
these disorders because most patients respond to oral administration of CoQ10.
PMID- 25126049
TI - Pathomechanisms in coenzyme q10-deficient human fibroblasts.
AB - Primary coenzyme Q10 (CoQ10) deficiency is a rare mitochondrial disorder
associated with 5 major clinical phenotypes: (1) encephalomyopathy, (2) severe
infantile multisystemic disease, (3) cerebellar ataxia, (4) isolated myopathy,
and (5) steroid-resistant nephrotic syndrome. Growth retardation, deafness and
hearing loss have also been described in CoQ10-deficient patients. This
heterogeneity in the clinical presentations suggests that multiple
pathomechanisms may exist. To investigate the biochemical and molecular
consequences of CoQ10 deficiency, different laboratories have studied cultures of
skin fibroblasts from patients with CoQ10 deficiency. In this review, we
summarize the results obtained in these studies over the last decade.
PMID- 25126050
TI - Invertebrate models for coenzyme q10 deficiency.
AB - The human syndrome of coenzyme Q (CoQ) deficiency is a heterogeneous
mitochondrial disease characterized by a diminution of CoQ content in cells and
tissues that affects all the electron transport processes CoQ is responsible for,
like the electron transference in mitochondria for respiration and ATP production
and the antioxidant capacity that it exerts in membranes and lipoproteins.
Supplementation with external CoQ is the main attempt to address these
pathologies, but quite variable results have been obtained ranging from little
response to a dramatic recovery. Here, we present the importance of modeling
human CoQ deficiencies in animal models to understand the genetics and the
pathology of this disease, although the election of an organism is crucial and
can sometimes be controversial. Bacteria and yeast harboring mutations that lead
to CoQ deficiency are unable to grow if they have to respire but develop without
any problems on media with fermentable carbon sources. The complete lack of CoQ
in mammals causes embryonic lethality, whereas other mutations produce tissue
specific diseases as in humans. However, working with transgenic mammals is time
and cost intensive, with no assurance of obtaining results. Caenorhabditis
elegans and Drosophila melanogaster have been used for years as organisms to
study embryonic development, biogenesis, degenerative pathologies, and aging
because of the genetic facilities and the speed of working with these animal
models. In this review, we summarize several attempts to model reliable human CoQ
deficiencies in invertebrates, focusing on mutant phenotypes pretty similar to
those observed in human patients.
PMID- 25126051
TI - An overview of current mouse models recapitulating coenzyme q10 deficiency
syndrome.
AB - Coenzyme Q (CoQ), also known as ubiquinone, is an essential lipophilic molecule
present in all cellular membranes and involved in a variety of cellular
functions, in particular as an electron carrier in the mitochondrial respiratory
chain and as a potent antioxidant. CoQ is synthesized endogenously through a
complex metabolic pathway involving over 10 different components. Primary CoQ10
deficiency in humans, due to mutations in genes involved in CoQ biosynthesis, is
a heterogeneous group of rare disorders presenting severe and complex clinical
symptoms. The generation of mouse models deficient in CoQ is important to further
clarify the cellular function of CoQ and to unravel the complexity in the
pathophysiological consequences of CoQ deficiency. This review summarizes the
current knowledge on mouse models of primary CoQ deficiency.
PMID- 25126053
TI - Learning with repeated-game strategies.
AB - We use the self-tuning Experience Weighted Attraction model with repeated-game
strategies as a computer testbed to examine the relative frequency, speed of
convergence and progression of a set of repeated-game strategies in four
symmetric 2 * 2 games: Prisoner's Dilemma, Battle of the Sexes, Stag-Hunt, and
Chicken. In the Prisoner's Dilemma game, we find that the strategy with the most
occurrences is the "Grim-Trigger." In the Battle of the Sexes game, a cooperative
pair that alternates between the two pure-strategy Nash equilibria emerges as the
one with the most occurrences. In the Stag-Hunt and Chicken games, the "Win-Stay,
Lose-Shift" and "Grim-Trigger" strategies are the ones with the most occurrences.
Overall, the pairs that converged quickly ended up at the cooperative outcomes,
whereas the ones that were extremely slow to reach convergence ended up at non
cooperative outcomes.
PMID- 25126052
TI - Coenzyme q10 therapy.
AB - For a number of years, coenzyme Q10 (CoQ10) was known for its key role in
mitochondrial bioenergetics; later studies demonstrated its presence in other
subcellular fractions and in blood plasma, and extensively investigated its
antioxidant role. These 2 functions constitute the basis for supporting the
clinical use of CoQ10. Also, at the inner mitochondrial membrane level, CoQ10 is
recognized as an obligatory cofactor for the function of uncoupling proteins and
a modulator of the mitochondrial transition pore. Furthermore, recent data
indicate that CoQ10 affects the expression of genes involved in human cell
signaling, metabolism and transport, and some of the effects of CoQ10
supplementation may be due to this property. CoQ10 deficiencies are due to
autosomal recessive mutations, mitochondrial diseases, aging-related oxidative
stress and carcinogenesis processes, and also statin treatment. Many
neurodegenerative disorders, diabetes, cancer, and muscular and cardiovascular
diseases have been associated with low CoQ10 levels as well as different ataxias
and encephalomyopathies. CoQ10 treatment does not cause serious adverse effects
in humans and new formulations have been developed that increase CoQ10 absorption
and tissue distribution. Oral administration of CoQ10 is a frequent antioxidant
strategy in many diseases that may provide a significant symptomatic benefit.
PMID- 25126055
TI - Gender differences in the temporal voice areas.
AB - There is not only evidence for behavioral differences in voice perception between
female and male listeners, but also recent suggestions for differences in neural
correlates between genders. The fMRI functional voice localizer (comprising a
univariate analysis contrasting stimulation with vocal vs. non-vocal sounds) is
known to give robust estimates of the temporal voice areas (TVAs). However, there
is growing interest in employing multivariate analysis approaches to fMRI data
(e.g., multivariate pattern analysis; MVPA). The aim of the current study was to
localize voice-related areas in both female and male listeners and to investigate
whether brain maps may differ depending on the gender of the listener. After a
univariate analysis, a random effects analysis was performed on female (n = 149)
and male (n = 123) listeners and contrasts between them were computed. In
addition, MVPA with a whole-brain searchlight approach was implemented and
classification maps were entered into a second-level permutation based random
effects models using statistical non-parametric mapping (SnPM; Nichols and
Holmes, 2002). Gender differences were found only in the MVPA. Identified regions
were located in the middle part of the middle temporal gyrus (bilateral) and the
middle superior temporal gyrus (right hemisphere). Our results suggest
differences in classifier performance between genders in response to the voice
localizer with higher classification accuracy from local BOLD signal patterns in
several temporal-lobe regions in female listeners.
PMID- 25126054
TI - A comprehensive assessment of resting state networks: bidirectional modification
of functional integrity in cerebro-cerebellar networks in dementia.
AB - In resting state fMRI (rs-fMRI), only functional connectivity (FC) reductions in
the default mode network (DMN) are normally reported as a biomarker for
Alzheimer's disease (AD). In this investigation we have developed a comprehensive
strategy to characterize the FC changes occurring in multiple networks and
applied it in a pilot study of subjects with AD and Mild Cognitive Impairment
(MCI), compared to healthy controls (HC). Resting state networks (RSNs) were
studied in 14 AD (70 +/- 6 years), 12 MCI (74 +/- 6 years), and 16 HC (69 +/- 5
years). RSN alterations were present in almost all the 15 recognized RSNs;
overall, 474 voxels presented a reduced FC in MCI and 1244 in AD while 1627
voxels showed an increased FC in MCI and 1711 in AD. The RSNs were then ranked
according to the magnitude and extension of FC changes (gFC), putting in evidence
6 RSNs with prominent changes: DMN, frontal cortical network (FCN), lateral
visual network (LVN), basal ganglia network (BGN), cerebellar network (CBLN), and
the anterior insula network (AIN). Nodes, or hubs, showing alterations common to
more than one RSN were mostly localized within the prefrontal cortex and the
mesial-temporal cortex. The cerebellum showed a unique behavior where voxels of
decreased gFC were only found in AD while a significant gFC increase was only
found in MCI. The gFC alterations showed strong correlations (p < 0.001) with
psychological scores, in particular Mini-Mental State Examination (MMSE) and
attention/memory tasks. In conclusion, this analysis revealed that the DMN was
affected by remarkable FC increases, that FC alterations extended over several
RSNs, that derangement of functional relationships between multiple areas
occurred already in the early stages of dementia. These results warrant future
work to verify whether these represent compensatory mechanisms that exploit a pre
existing neural reserve through plasticity, which evolve in a state of lack of
connectivity between different networks with the worsening of the pathology.
PMID- 25126057
TI - Two distinct olfactory bulb sublaminar networks involved in gamma and beta
oscillation generation: a CSD study in the anesthetized rat.
AB - A prominent feature of olfactory bulb (OB) dynamics is the expression of
characteristic local field potential (LFP) rhythms, including a slow respiration
related rhythm and two fast alternating oscillatory rhythms, beta (15-30 Hz) and
gamma (40-90 Hz). All of these rhythms are implicated in olfactory coding. Fast
oscillatory rhythms are known to involve the mitral-granule cell loop. Although
the underlying mechanisms of gamma oscillation have been studied, the origin of
beta oscillation remains poorly understood. Whether these two different rhythms
share the same underlying mechanism is unknown. This study uses a quantitative
and detailed current-source density (CSD) analysis combined with multi-unit
activity (MUA) recordings to shed light on this question in freely breathing
anesthetized rats. In particular, we show that gamma oscillation generation
involves mainly the upper half of the external plexiform layer (EPL) and
superficial areas of granule cell layer (GRL). In contrast, the generation of
beta oscillation involves the lower part of the EPL and deep granule cells. This
differential involvement of sublaminar networks is neither dependent on odor
quality nor on the precise frequency of the fast oscillation under study.
Overall, this study demonstrates a functional sublaminar organization of the rat
OB, which is supported by previous anatomical findings.
PMID- 25126058
TI - Across-ear stimulus-specific adaptation in the auditory cortex.
AB - The ability to detect unexpected or deviant events in natural scenes is critical
for survival. In the auditory system, neurons from the midbrain to cortex adapt
quickly to repeated stimuli but this adaptation does not fully generalize to
other rare stimuli, a phenomenon called stimulus-specific adaptation (SSA). Most
studies of SSA were conducted with pure tones of different frequencies, and it is
by now well-established that SSA to tone frequency is strong and robust in
auditory cortex. Here we tested SSA in the auditory cortex to the ear of
stimulation using broadband noise. We show that cortical neurons adapt
specifically to the ear of stimulation, and that the contrast between the
responses to stimulation of the same ear when rare and when common depends on the
binaural interaction class of the neurons.
PMID- 25126056
TI - Frontiers in therapeutic development of allopregnanolone for Alzheimer's disease
and other neurological disorders.
AB - Allopregnanolone (Allo), a neurosteroid, has emerged as a promising promoter of
endogenous regeneration in brain. In a mouse model of Alzheimer's disease, Allo
induced neurogenesis, oligodendrogenesis, white matter generation and cholesterol
homeostasis while simultaneously reducing beta-amyloid and neuroinflammatory
burden. Allo activates signaling pathways and gene expression required for
regeneration of neural stem cells and their differentiation into neurons. In
parallel, Allo activates systems to sustain cholesterol homeostasis and reduce
beta-amyloid generation. To advance Allo into studies for chronic human
neurological conditions, we examined translational and clinical parameters: dose,
regimen, route, formulation, outcome measures, and safety regulations. A
treatment regimen of once per week at sub-sedative doses of Allo was optimal for
regeneration and reduction in Alzheimer's pathology. This regimen had a high
safety profile following chronic exposure in aged normal and Alzheimer's mice.
Formulation of Allo for multiple routes of administration has been developed for
both preclinical and clinical testing. Preclinical evidence for therapeutic
efficacy of Allo spans multiple neurological diseases including Alzheimer's,
Parkinson's, multiple sclerosis, Niemann-Pick, diabetic neuropathy, status
epilepticus, and traumatic brain injury. To successfully translate Allo as a
therapeutic for multiple neurological disorders, it will be necessary to tailor
dose and regimen to the targeted therapeutic mechanisms and disease etiology.
Treatment paradigms conducted in accelerated disease models in young animals have
a low probability of successful translation to chronic diseases in adult and aged
humans. Gender, genetic risks, stage and burden of disease are critical
determinants of efficacy. This review focuses on recent advances in development
of Allo for Alzheimer's disease (AD) that have the potential to accelerate
therapeutic translation for multiple unmet neurological needs.
PMID- 25126059
TI - The world according to zebrafish: how neural circuits generate behavior.
PMID- 25126061
TI - Ethical issues with brain-computer interfaces.
PMID- 25126062
TI - Mice with a naturally occurring DISC1 mutation display a broad spectrum of
behaviors associated to psychiatric disorders.
AB - Disrupted in schizophrenia-1 (DISC1) gene is associated with several
neuropsychiatric disorders as it is disrupted by a balanced translocation
involving chromosomes 1 and 11 in a large Scottish pedigree with high prevalence
of schizophrenia, bipolar disorder and major depression. Since its
identification, several mouse models with DISC1 genetic modifications have been
generated using different approaches. Interestingly, a natural deletion of 25bp
in the 129 mouse strain alters the DISC1 gene reading frame leading to a
premature stop codon very close to the gene breakpoint in the mutant allele of
the Scottish family. In the present study we confirmed that the 129DISC1(Del)
mutation results in reduced level of full length DISC1 in hippocampus of
heterozygous mice and we have characterized the behavioral consequences of
heterozygous 129DISC1(Del) mutation in a mixed B6129 genetic background. We found
alterations in spontaneous locomotor activity (hyperactivity in males and
hypoactivity in females), deficits in pre-pulse inhibition (PPI) and also
increased despair behavior in heterozygous 129DISC1(Del) mice, thus reproducing
typical behaviors associated to psychiatric disorders. Since this mouse strain is
widely and commercially available, we propose it as an amenable tool to study
DISC1-related biochemical alterations and psychiatric behaviors.
PMID- 25126060
TI - Best of both worlds: promise of combining brain stimulation and brain connectome.
AB - Transcranial current brain stimulation (tCS) is becoming increasingly popular as
a non-pharmacological non-invasive neuromodulatory method that alters cortical
excitability by applying weak electrical currents to the scalp via a pair of
electrodes. Most applications of this technique have focused on enhancing motor
and learning skills, as well as a therapeutic agent in neurological and
psychiatric disorders. In these applications, similarly to lesion studies, tCS
was used to provide a causal link between a function or behavior and a specific
brain region (e.g., primary motor cortex). Nonetheless, complex cognitive
functions are known to rely on functionally connected multitude of brain regions
with dynamically changing patterns of information flow rather than on isolated
areas, which are most commonly targeted in typical tCS experiments. In this
review article, we argue in favor of combining tCS method with other neuroimaging
techniques (e.g., fMRI, EEG) and by employing state-of-the-art connectivity data
analysis techniques (e.g., graph theory) to obtain a deeper understanding of the
underlying spatiotemporal dynamics of functional connectivity patterns and
cognitive performance. Finally, we discuss the possibilities of using these
combined techniques to investigate the neural correlates of human creativity and
to enhance creativity.
PMID- 25126063
TI - Differential effects of sertraline in a predator exposure animal model of post
traumatic stress disorder.
AB - Serotonin (5-HT), norepinephrine (NE), and other neurotransmitters are modulated
in post-traumatic stress disorder (PTSD). In addition, pro-inflammatory cytokines
(PIC) are elevated during the progression of the disorder. Currently, the only
approved pharmacologic treatments for PTSD are the selective-serotonin reuptake
inhibitors (SSRI) sertraline and paroxetine, but their efficacy in treating PTSD
is marginal at best. In combat-related PTSD, SSRIs are of limited effectiveness.
Thus, this study sought to analyze the effects of the SSRI sertraline on
inflammation and neurotransmitter modulation via a predator exposure/psychosocial
stress animal model of PTSD. We hypothesized that sertraline would diminish
inflammatory components and increase 5-HT but might also affect levels of other
neurotransmitters, particularly NE. PTSD-like effects were induced in male
Sprague-Dawley rats (n = 6/group * 4 groups). The rats were secured in Plexiglas
cylinders and placed in a cage with a cat for 1 h on days 1 and 11 of a 31-day
stress regimen. PTSD rats were also subjected to psychosocial stress via daily
cage cohort changes. At the conclusion of the stress regimen, treatment group
animals were injected intraperitoneally (i.p.) with sertraline HCl at 10 mg/kg
for 7 consecutive days, while controls received i.p. vehicle. The animals were
subsequently sacrificed on day 8. Sertraline attenuated inflammatory markers and
normalized 5-HT levels in the central nervous system (CNS). In contrast,
sertraline produced elevations in NE in the CNS and systemic circulation of SSRI
treated PTSD and control groups. This increase in NE suggests SSRIs produce a
heightened noradrenergic response, which might elevate anxiety in a clinical
setting.
PMID- 25126065
TI - Learning to perceive in the sensorimotor approach: Piaget's theory of
equilibration interpreted dynamically.
AB - LEARNING TO PERCEIVE IS FACED WITH A CLASSICAL PARADOX: if understanding is
required for perception, how can we learn to perceive something new, something we
do not yet understand? According to the sensorimotor approach, perception
involves mastery of regular sensorimotor co-variations that depend on the agent
and the environment, also known as the "laws" of sensorimotor contingencies
(SMCs). In this sense, perception involves enacting relevant sensorimotor skills
in each situation. It is important for this proposal that such skills can be
learned and refined with experience and yet up to this date, the sensorimotor
approach has had no explicit theory of perceptual learning. The situation is made
more complex if we acknowledge the open-ended nature of human learning. In this
paper we propose Piaget's theory of equilibration as a potential candidate to
fulfill this role. This theory highlights the importance of intrinsic
sensorimotor norms, in terms of the closure of sensorimotor schemes. It also
explains how the equilibration of a sensorimotor organization faced with novelty
or breakdowns proceeds by re-shaping pre-existing structures in coupling with
dynamical regularities of the world. This way learning to perceive is guided by
the equilibration of emerging forms of skillful coping with the world. We
demonstrate the compatibility between Piaget's theory and the sensorimotor
approach by providing a dynamical formalization of equilibration to give an
explicit micro-genetic account of sensorimotor learning and, by extension, of how
we learn to perceive. This allows us to draw important lessons in the form of
general principles for open-ended sensorimotor learning, including the need for
an intrinsic normative evaluation by the agent itself. We also explore
implications of our micro-genetic account at the personal level.
PMID- 25126064
TI - Parallel processing in the brain's visual form system: an fMRI study.
AB - We here extend and complement our earlier time-based, magneto-encephalographic
(MEG), study of the processing of forms by the visual brain (Shigihara and Zeki,
2013) with a functional magnetic resonance imaging (fMRI) study, in order to
better localize the activity produced in early visual areas when subjects view
simple geometric stimuli of increasing perceptual complexity (lines, angles,
rhombuses) constituted from the same elements (lines). Our results show that all
three categories of form activate all three visual areas with which we were
principally concerned (V1-V3), with angles producing the strongest and rhombuses
the weakest activity in all three. The difference between the activity produced
by angles and rhombuses was significant, that between lines and rhombuses was
trend significant while that between lines and angles was not. Taken together
with our earlier MEG results, the present ones suggest that a parallel strategy
is used in processing forms, in addition to the well-documented hierarchical
strategy.
PMID- 25126066
TI - Different corticospinal control between discrete and rhythmic movement of the
ankle.
AB - We investigated differences in corticospinal and spinal control between discrete
and rhythmic ankle movements. Motor evoked potentials (MEPs) in the tibialis
anterior and soleus muscles and soleus H-reflex were elicited in the middle of
the plantar flexion phase during discrete ankle movement or in the initial or
later cycles of rhythmic ankle movement. The H-reflex was evoked at an intensity
eliciting a small M-wave and MEPs were elicited at an intensity of 1.2 times the
motor threshold of the soleus MEPs. Only trials in which background EMG level,
ankle angle, and ankle velocity were similar among the movement conditions were
included for data analysis. In addition, only trials with a similar M-wave were
included for data analysis in the experiment evoking H-reflexes. Results showed
that H reflex and MEP amplitudes in the soleus muscle during discrete movement
were not significantly different from those during rhythmic movement. MEP
amplitude in the tibialis anterior muscle during the later cycles of rhythmic
movement was significantly larger than that during the initial cycle of the
rhythmic movement or during discrete movement. Higher corticospinal excitability
in the tibialis anterior muscle during the later cycles of rhythmic movement may
reflect changes in corticospinal control from the initial cycle to the later
cycles of rhythmic movement.
PMID- 25126067
TI - Analysis of sampling artifacts on the Granger causality analysis for topology
extraction of neuronal dynamics.
AB - Granger causality (GC) is a powerful method for causal inference for time series.
In general, the GC value is computed using discrete time series sampled from
continuous-time processes with a certain sampling interval length tau, i.e., the
GC value is a function of tau. Using the GC analysis for the topology extraction
of the simplest integrate-and-fire neuronal network of two neurons, we discuss
behaviors of the GC value as a function of tau, which exhibits (i) oscillations,
often vanishing at certain finite sampling interval lengths, (ii) the GC vanishes
linearly as one uses finer and finer sampling. We show that these sampling
effects can occur in both linear and non-linear dynamics: the GC value may vanish
in the presence of true causal influence or become non-zero in the absence of
causal influence. Without properly taking this issue into account, GC analysis
may produce unreliable conclusions about causal influence when applied to
empirical data. These sampling artifacts on the GC value greatly complicate the
reliability of causal inference using the GC analysis, in general, and the
validity of topology reconstruction for networks, in particular. We use idealized
linear models to illustrate possible mechanisms underlying these phenomena and to
gain insight into the general spectral structures that give rise to these
sampling effects. Finally, we present an approach to circumvent these sampling
artifacts to obtain reliable GC values.
PMID- 25126068
TI - Ventral-stream-like shape representation: from pixel intensity values to
trainable object-selective COSFIRE models.
AB - The remarkable abilities of the primate visual system have inspired the
construction of computational models of some visual neurons. We propose a
trainable hierarchical object recognition model, which we call S-COSFIRE (S
stands for Shape and COSFIRE stands for Combination Of Shifted FIlter REsponses)
and use it to localize and recognize objects of interests embedded in complex
scenes. It is inspired by the visual processing in the ventral stream (V1/V2 ->
V4 -> TEO). Recognition and localization of objects embedded in complex scenes is
important for many computer vision applications. Most existing methods require
prior segmentation of the objects from the background which on its turn requires
recognition. An S-COSFIRE filter is automatically configured to be selective for
an arrangement of contour-based features that belong to a prototype shape
specified by an example. The configuration comprises selecting relevant vertex
detectors and determining certain blur and shift parameters. The response is
computed as the weighted geometric mean of the blurred and shifted responses of
the selected vertex detectors. S-COSFIRE filters share similar properties with
some neurons in inferotemporal cortex, which provided inspiration for this work.
We demonstrate the effectiveness of S-COSFIRE filters in two applications: letter
and keyword spotting in handwritten manuscripts and object spotting in complex
scenes for the computer vision system of a domestic robot. S-COSFIRE filters are
effective to recognize and localize (deformable) objects in images of complex
scenes without requiring prior segmentation. They are versatile trainable shape
detectors, conceptually simple and easy to implement. The presented hierarchical
shape representation contributes to a better understanding of the brain and to
more robust computer vision algorithms.
PMID- 25126069
TI - Pydpiper: a flexible toolkit for constructing novel registration pipelines.
AB - Using neuroimaging technologies to elucidate the relationship between genotype
and phenotype and brain and behavior will be a key contribution to biomedical
research in the twenty-first century. Among the many methods for analyzing
neuroimaging data, image registration deserves particular attention due to its
wide range of applications. Finding strategies to register together many images
and analyze the differences between them can be a challenge, particularly given
that different experimental designs require different registration strategies.
Moreover, writing software that can handle different types of image registration
pipelines in a flexible, reusable and extensible way can be challenging. In
response to this challenge, we have created Pydpiper, a neuroimaging registration
toolkit written in Python. Pydpiper is an open-source, freely available software
package that provides multiple modules for various image registration
applications. Pydpiper offers five key innovations. Specifically: (1) a robust
file handling class that allows access to outputs from all stages of registration
at any point in the pipeline; (2) the ability of the framework to eliminate
duplicate stages; (3) reusable, easy to subclass modules; (4) a development
toolkit written for non-developers; (5) four complete applications that run
complex image registration pipelines "out-of-the-box." In this paper, we will
discuss both the general Pydpiper framework and the various ways in which
component modules can be pieced together to easily create new registration
pipelines. This will include a discussion of the core principles motivating code
development and a comparison of Pydpiper with other available toolkits. We also
provide a comprehensive, line-by-line example to orient users with limited
programming knowledge and highlight some of the most useful features of Pydpiper.
In addition, we will present the four current applications of the code.
PMID- 25126070
TI - An intraductal papillary neoplasm of the bile duct at the duodenal papilla.
AB - In recent years, the disease concept of intraductal papillary neoplasm of the
bile duct (IPNB) has been attracting attention as a biliary lesion that is
morphologically similar to intraductal papillary mucinous neoplasm (IPMN), which
is considered to be a counterpart of IPMN. However, there are few reports on
IPNB, and a consensus regarding the features of this disease is thus lacking. We
experienced an extremely rare case of IPNB occurring in the bile duct at the
duodenal papilla, which is a tumor presentation that has not previously been
reported. Herein, we report this interesting case and discuss the possible
association between IPMN and IPNB.
PMID- 25126071
TI - Asymptomatic pelvic metastasis from thymic carcinoma: a case report.
AB - Thymic epithelial tumors are rare and often occur somewhere local. Metastatic
sites of thymic carcinomas (Masaoka-Koga stage IVb) are mostly seen in the lung,
liver and brain. We report a 64-year-old female with an initial diagnosis of
thymoma B3 who first showed thoracic recurrences and then an asymptomatic
isolated pelvic metastasis from her thymic carcinoma.
PMID- 25126072
TI - A Report of Disseminated Carcinomatosis of the Bone Marrow Originating from
Transverse Colon Cancer Successfully Treated with Chemotherapy Using XELOX plus
Bevacizumab.
AB - A 61-year-old male, who had been admitted to another hospital due to disseminated
intravascular coagulation (DIC), was referred to our hospital. Total colonoscopy,
abdominal dynamic CT and positron-emission tomography revealed bone metastasis
and multiple lymphocytic metastases from transverse colon cancer in addition to
disseminated carcinomatosis of the bone marrow (DCBM). We immediately performed
chemotherapy with XELOX + bevacizumab and denosumab against DCBM from transverse
colon cancer in order to avoid radical surgery. In addition, we initiated the
administration of recombinant human soluble thrombomodulin for 1 week to treat
DIC. The patient was able to tolerate and receive 4 cycles of chemotherapy
without any severe side effects. After receiving the 4 cycles of treatment, he
recovered from DIC, and the bone and multiple lymphocytic metastases disappeared.
PMID- 25126074
TI - Repeat Descemetopexy after Descemet's Membrane Detachment following
Phacoemulsification.
AB - Descemet's membrane detachment (DMD) is an uncommon condition with a wide range
of possible etiologies. Probably the commonest cause is a localized detachment
occurring after cataract extraction surgery. Descemetopexy gives good anatomic
attachment rates and visual outcomes and has become the standard treatment for
DMD. However, in cases with failed initial descemetopexy, the next step in the
management of such cases remains unclear. Before initiating a complex surgical
procedure like keratoplasty, which requires good postoperative care and regular
follow-ups, repeat descemetopexy with a long-term tamponade using 14% C3F8 gas
for recurrent DMD is definitely a worthwhile attempt.
PMID- 25126075
TI - Hemorrhagic macular infarction after intravitreal bevacizumab for chronic
multifocal central serous chorioretinopathy.
AB - We hereby report a case of hemorrhagic macular infarction after intravitreal
bevacizumab for chronic multifocal central serous chorioretinopathy (CSC). Issues
regarding safety and adverse effects of bevacizumab are discussed. To the best of
our knowledge, this is the first reported case of hemorrhagic macular infarction
after intravitreal bevacizumab for chronic multifocal CSC.
PMID- 25126073
TI - A Prospective Phase I/II Study: Combination Chemotherapy with Docetaxel and
Pemetrexed as Second-Line Treatment in Patients with Stage IIIB/IV Non-Small Cell
Lung Cancer.
AB - INTRODUCTION: Two standard single-agent chemotherapy treatments (docetaxel and
pemetrexed) were combined in this trial and administered as second-line treatment
in patients with non-small cell lung cancer (NSCLC). The aim of this study was to
evaluate the safety and feasibility of combining docetaxel with pemetrexed.
METHODS: Six patients were enrolled between August 2007 and March 2009 with stage
IIIB/IV NSCLC. The dose-escalation model included a pemetrexed infusion on day 1
of 200-300 mg/m(2) followed by infusion of docetaxel on days 1, 8 and 15 at doses
from 20 to 30 mg/m(2). Primary study endpoints included efficacy and safety
variables, also progression-free, overall and 1-year survival and time to
progression. RESULTS: The study was abandoned due to adverse effects defined in
the protocol. The major toxicities were all of grade 3 and included fatigue,
stomatitis/mucositis, diarrhea and in one case, an episode of febrile
neutropenia. Two patients died during the study, but not as a direct result of
the treatment. CONCLUSIONS: We recommend that docetaxel or pemetrexed
monotherapies should continue to be considered the standard second-line
chemotherapy treatment against NSCLC. The results of this study warrant no
further investigation into this particular combination treatment due to the
severe toxicity effects encountered.
PMID- 25126076
TI - Haptic breakage after transscleral fixation of a single-piece acrylic intraocular
lens.
AB - PURPOSE: To report the case of a patient with a damaged haptic of an acrylic
intraocular lens (IOL) after transscleral IOL fixation. METHODS: This is a
retrospective and descriptive case report. RESULTS: A 40-year-old man presented
with sudden visual loss in the left eye. He had undergone
phacoemulsification/aspiration and IOL implantation 3 years previously and IOL
repositioning with transscleral fixation 2 years before the initial visit. His
visual acuity was 0.3 in the left eye due to corneal edema caused by a foreign
body, i.e., the severed haptic tip of the single-piece acrylic IOL, which was
surgically removed. The IOL itself was tilted and therefore explanted. The
surface of the tip of the haptic suggested that the monofilament suture thread
had exerted continuous force across the haptic. CONCLUSIONS: The haptics of
acrylic IOLs can be damaged after transscleral fixation.
PMID- 25126077
TI - A new clinical tool for assessing numerical abilities in neurological diseases:
numerical activities of daily living.
AB - The aim of this study was to build an instrument, the numerical activities of
daily living (NADL), designed to identify the specific impairments in numerical
functions that may cause problems in everyday life. These impairments go beyond
what can be inferred from the available scales evaluating activities of daily
living in general, and are not adequately captured by measures of the general
deterioration of cognitive functions as assessed by standard clinical instruments
like the MMSE and MoCA. We assessed a control group (n = 148) and a patient group
affected by a wide variety of neurological conditions (n = 175), with NADL along
with IADL, MMSE, and MoCA. The NADL battery was found to have satisfactory
construct validity and reliability, across a wide age range. This enabled us to
calculate appropriate criteria for impairment that took into account age and
education. It was found that neurological patients tended to overestimate their
abilities as compared to the judgment made by their caregivers, assessed with
objective tests of numerical abilities.
PMID- 25126078
TI - Lithium suppresses Abeta pathology by inhibiting translation in an adult
Drosophila model of Alzheimer's disease.
AB - The greatest risk factor for Alzheimer's disease (AD) is age, and changes in the
ageing nervous system are likely contributors to AD pathology. Amyloid beta
(Abeta) accumulation, which occurs as a result of the amyloidogenic processing of
amyloid precursor protein (APP), is thought to initiate the pathogenesis of AD,
eventually leading to neuronal cell death. Previously, we developed an adult
onset Drosophila model of AD. Mutant Abeta42 accumulation led to increased
mortality and neuronal dysfunction in the adult flies. Furthermore, we showed
that lithium reduced Abeta42 protein, but not mRNA, and was able to rescue
Abeta42-induced toxicity. In the current study, we investigated the mechanism/s
by which lithium modulates Abeta42 protein levels and Abeta42 induced toxicity in
the fly model. We found that lithium caused a reduction in protein synthesis in
Drosophila and hence the level of Abeta42. At both the low and high doses tested,
lithium rescued the locomotory defects induced by Abeta42, but it rescued
lifespan only at lower doses, suggesting that long-term, high-dose lithium
treatment may have induced toxicity. Lithium also down-regulated translation in
the fission yeast Schizosaccharomyces pombe associated with increased
chronological lifespan. Our data highlight a role for lithium and reduced protein
synthesis as potential therapeutic targets for AD pathogenesis.
PMID- 25126079
TI - RNA Transcription and Maturation in Skeletal Muscle Cells are Similarly Impaired
in Myotonic Dystrophy and Sarcopenia: The Ultrastructural Evidence.
PMID- 25126080
TI - Expression of the prostaglandin F synthase AKR1B1 and the prostaglandin
transporter SLCO2A1 in human fetal membranes in relation to spontaneous term and
preterm labor.
AB - BACKGROUND: Human labor is a complex series of cellular and molecular events that
occur at the materno-fetal and uterine levels. Many hypotheses have been proposed
for the initiation of human labor, one hypothesis suggests that maturation of the
fetus releases a signal in the amniotic fluid that will be transmitted to
myometrium via the fetal membranes and initiate uterine contractions. There is
strong evidence that prostaglandins (PGs) play a central role in initiation and
progression of human labor. OBJECTIVES: In this study we intended to investigate
the expression of prostaglandin F synthase and the prostaglandin transporter in
the human fetal membranes and to explore the relationship between cytokines and
PGs in the mechanism of human labor. METHODS: We used fetal membranes obtained
before labor at term and after spontaneous labor at term or preterm to identify
the changes in prostaglandin F synthase (AKR1B1) and human prostaglandin
transporter (SLCO2A1) proteins in relation to parturition. Using fetal membranes
explants we tested the effect of cytokines (interleukin-1 and tumor necrosis
factor alpha) on PG production and the concomitant changes in cyclooxygenase-2
(PTGS2), AKR1B1 and SLCO2A1 expression. RESULTS: Expression of PTGS2 and AKR1B1
was upregulated in the fetal membranes in association with term labor while
SLCO2A1 was downregulated with advancing gestation and during term labor. Before
labor, IL-1 increased the expression of PTGS2, however during labor TNF
upregulated PTGS2 and AKR1B1 proteins. CONCLUSIONS: The prostaglandin F synthase
AKR1B1 is upregulated while prostaglandin transporter is downregulated during
term labor. The amnion is more responsive than choriodecidua to stimulation with
pro-inflammatory cytokines. The mechanisms of term and preterm labor are
different.
PMID- 25126081
TI - Waves of visibility: probing the depth of inter-ocular suppression with transient
and sustained targets.
AB - In order to study non-conscious visual processing, researchers render otherwise
consciously perceived images into invisible stimuli. Through the years, several
psychophysical techniques have been developed for this purpose. Yet the
comparison of experimental results across techniques remains a difficult task as
the depth of suppression depends on the interactions between the type of stimuli
and the suppression methods employed. This poses a limit to the inferences that
researchers make about the extent of non-conscious processes. We investigated the
mechanisms underlying inter-ocular suppression during continuous flash
suppression (CFS) and dichoptic visual masking using a transient onset target
stimulus and a variety of stimulus/mask temporal manipulations. We show that
target duration, timing of target onset, and mask frequency are key aspects of
inter-ocular suppression during CFS with transient targets. The differences
between our results and sustained target CFS studies suggest that two distinct
mechanisms are involved in the detection of transient and prolonged target
stimuli during CFS. Our results provide insight into the dynamics of CFS together
with evidence for similarities between transient target CFS and dichoptic visual
masking.
PMID- 25126082
TI - The cortical microstructural basis of lateralized cognition: a review.
AB - The presence of asymmetry in the human cerebral hemispheres is detectable at both
the macroscopic and microscopic scales. The horizontal expansion of cortical
surface during development (within individual brains), and across evolutionary
time (between species), is largely due to the proliferation and spacing of the
microscopic vertical columns of cells that form the cortex. In the asymmetric
planum temporale (PT), minicolumn width asymmetry is associated with surface area
asymmetry. Although the human minicolumn asymmetry is not large, it is estimated
to account for a surface area asymmetry of approximately 9% of the region's size.
Critically, this asymmetry of minicolumns is absent in the equivalent areas of
the brains of other apes. The left-hemisphere dominance for processing speech is
thought to depend, partly, on a bias for higher resolution processing across
widely spaced minicolumns with less overlapping dendritic fields, whereas dense
minicolumn spacing in the right hemisphere is associated with more overlapping,
lower resolution, holistic processing. This concept refines the simple notion
that a larger brain area is associated with dominance for a function and offers
an alternative explanation associated with "processing type." This account is
mechanistic in the sense that it offers a mechanism whereby asymmetrical
components of structure are related to specific functional biases yielding
testable predictions, rather than the generalization that "bigger is better" for
any given function. Face processing provides a test case - it is the opposite of
language, being dominant in the right hemisphere. Consistent with the bias for
holistic, configural processing of faces, the minicolumns in the right-hemisphere
fusiform gyrus are thinner than in the left hemisphere, which is associated with
featural processing. Again, this asymmetry is not found in chimpanzees. The
difference between hemispheres may also be seen in terms of processing speed,
facilitated by asymmetric myelination of white matter tracts (Anderson et al.,
1999 found that axons of the left posterior superior temporal lobe were more
thickly myelinated). By cross-referencing the differences between the active
fields of the two hemispheres, via tracts such as the corpus callosum, the
relationship of local features to global features may be encoded. The emergent
hierarchy of features within features is a recursive structure that may
functionally contribute to generativity - the ability to perceive and express
layers of structure and their relations to each other. The inference is that
recursive generativity, an essential component of language, reflects an
interaction between processing biases that may be traceable in the microstructure
of the cerebral cortex. Minicolumn organization in the PT and the prefrontal
cortex has been found to correlate with cognitive scores in humans. Altered
minicolumn organization is also observed in neuropsychiatric disorders including
autism and schizophrenia. Indeed, altered interhemispheric connections correlated
with minicolumn asymmetry in schizophrenia may relate to language-processing
anomalies that occur in the disorder. Schizophrenia is associated with over
interpretation of word meaning at the semantic level and over-interpretation of
relevance at the level of pragmatic competence, whereas autism is associated with
overly literal interpretation of word meaning and under-interpretation of social
relevance at the pragmatic level. Both appear to emerge from a disruption of the
ability to interpret layers of meaning and their relations to each other. This
may be a consequence of disequilibrium in the processing of local and global
features related to disorganization of minicolumnar units of processing.
PMID- 25126083
TI - Publication bias and the limited strength model of self-control: has the evidence
for ego depletion been overestimated?
AB - Few models of self-control have generated as much scientific interest as has the
limited strength model. One of the entailments of this model, the depletion
effect, is the expectation that acts of self-control will be less effective when
they follow prior acts of self-control. Results from a previous meta-analysis
concluded that the depletion effect is robust and medium in magnitude (d = 0.62).
However, when we applied methods for estimating and correcting for small-study
effects (such as publication bias) to the data from this previous meta-analysis
effort, we found very strong signals of publication bias, along with an
indication that the depletion effect is actually no different from zero. We
conclude that until greater certainty about the size of the depletion effect can
be established, circumspection about the existence of this phenomenon is
warranted, and that rather than elaborating on the model, research efforts should
focus on establishing whether the basic effect exists. We argue that the evidence
for the depletion effect is a useful case study for illustrating the dangers of
small-study effects as well as some of the possible tools for mitigating their
influence in psychological science.
PMID- 25126084
TI - "Not in their right mind": the relation of psychopathology to the quantity and
quality of creative thought.
AB - The empirical link between psychopathology and creativity is often correlational
and fraught with suspiciously causal interpretations. In this paper, we review
research in favor of the position that certain forms of psychopathology that
profoundly affect the neural substrates for rule-based thought (e.g.,
schizophrenia, bipolar disorder) can significantly influence the quantity of
creative production. Because highly productive individuals, irrespective of
psychopathology, often produce work of greater quality, it seems that such an
increase in the quantity of one's output positively affects the likelihood of
generating those statistically rare acts and achievements identified and
celebrated as creative. We consider evidence that offers support for such a
claim. In addition, we explore findings from neuroscience that can address how a
neural mechanism, the flexibility of which relies on tradeoffs between rule-based
(e.g., prefrontal cortex) and stimulus-based (e.g., sensorimotor cortex) brain
regions, is influenced by psychopathology in ways that can alter dramatically the
quantity and quality of creative output.
PMID- 25126086
TI - The role of the immune system in the pathogenesis of diabetic complications.
PMID- 25126085
TI - How Much Should We Weigh for a Long and Healthy Life Span? The Need to Reconcile
Caloric Restriction versus Longevity with Body Mass Index versus Mortality Data.
AB - Total caloric restriction (CR) without malnutrition is a well-established
experimental approach to extend life span in laboratory animals. Although CR in
humans is capable of shifting several endocrinological parameters, it is not
clear where the minimum inflection point of the U-shaped curve linking body mass
index (BMI) with all-cause mortality lies. The exact trend of this curve, when
used for planning preventive strategies for public health is of extreme
importance. Normal BMI ranges from 18.5 to 24.9; many epidemiological studies
show an inverse relationship between mortality and BMI inside the normal BMI
range. Other studies show that the lowest mortality in the entire range of BMI is
obtained in the overweight range (25-29.9). Reconciling the extension of life
span in laboratory animals by experimental CR with the BMI-mortality curve of
human epidemiology is not trivial. In fact, one interpretation is that the CR
data are identifying a known: "excess fat is deleterious for health"; although a
second interpretation may be that: "additional leanness from a normal body weight
may add health and life span delaying the process of aging." This short review
hope to start a discussion aimed at finding the widest consensus on which weight
range should be considered the "healthiest" for our species, contributing in this
way to the picture of what is the correct life style for a long and healthy life
span.
PMID- 25126088
TI - Invited commentary: lubricating the rusty wheel, new insights into iron oxidizing
bacteria through comparative genomics.
PMID- 25126090
TI - Nitrate transporters in leaves and their potential roles in foliar uptake of
nitrogen dioxide.
AB - While plant roots are specialized organs for the uptake and transport of water
and nutrients, the absorption of gaseous or liquid mineral elements by aerial
plant parts has been recognized since more than one century. Nitrogen (N) is an
essential macronutrient which generally absorbed either as nitrate (NO(-) 3) or
ammonium (NH(+) 4) by plant roots. Gaseous nitrogen pollutants like N dioxide
(NO2) can also be absorbed by plant surfaces and assimilated via the NO(-) 3
assimilation pathway. The subsequent NO(-) 3 flux may induce or repress the
expression of various NO(-) 3-responsive genes encoding for instance, the
transmembrane transporters, NO(-) 3/NO(-) 2 (nitrite) reductase, or assimilatory
enzymes involved in N metabolism. Based on the existing information, the aim of
this review was to theoretically analyze the potential link between foliar NO2
absorption and N transport and metabolism. For such purpose, an overview of the
state of knowledge on the NO(-) 3 transporter genes identified in leaves or
shoots of various species and their roles for NO(-) 3 transport across the
tonoplast and plasma membrane, in addition to the process of phloem loading is
briefly provided. It is assumed that a NO2-induced accumulation of NO(-) 3/NO(-)
2 may alter the expression of such genes, hence linking transmembrane NO(-) 3
transporters and foliar uptake of NO2. It is likely that NRT1/NRT2 gene
expression and species-dependent apoplastic buffer capacity may be also related
to the species-specific foliar NO2 uptake process. It is concluded that further
work focusing on the expression of NRT1 (NRT1.1, NRT1.7, NRT1.11, and NRT1.12),
NRT2 (NRT2.1, NRT2.4, and NRT2.5) and chloride channel family genes (CLCa and
CLCd) may help us elucidate the physiological and metabolic response of plants
fumigated with NO2.
PMID- 25126089
TI - Clearance of Apoptotic Bodies, NETs, and Biofilm DNA: Implications for
Autoimmunity.
PMID- 25126091
TI - Next generation sequencing technologies for next generation plant breeding.
PMID- 25126087
TI - Podocyte pathology and nephropathy - sphingolipids in glomerular diseases.
AB - Sphingolipids are components of the lipid rafts in plasma membranes, which are
important for proper function of podocytes, a key element of the glomerular
filtration barrier. Research revealed an essential role of sphingolipids and
sphingolipid metabolites in glomerular disorders of genetic and non-genetic
origin. The discovery that glucocerebrosides accumulate in Gaucher disease in
glomerular cells and are associated with clinical proteinuria initiated intensive
research into the function of other sphingolipids in glomerular disorders. The
accumulation of sphingolipids in other genetic diseases including Tay-Sachs,
Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann-Pick, and
nephrotic syndrome of the Finnish type and its implications with respect to
glomerular pathology will be discussed. Similarly, sphingolipid accumulation
occurs in glomerular diseases of non-genetic origin including diabetic kidney
disease (DKD), HIV-associated nephropathy, focal segmental glomerulosclerosis
(FSGS), and lupus nephritis. Sphingomyelin metabolites, such as ceramide,
sphingosine, and sphingosine-1-phosphate have also gained tremendous interest. We
recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is
expressed in podocytes where it modulates acid sphingomyelinase activity and acts
as a master modulator of danger signaling. Decreased SMPDL3b expression in post
reperfusion kidney biopsies from transplant recipients with idiopathic FSGS
correlates with the recurrence of proteinuria in patients and in experimental
models of xenotransplantation. Increased SMPDL3b expression is associated with
DKD. The consequences of differential SMPDL3b expression in podocytes in these
diseases with respect to their pathogenesis will be discussed. Finally, the role
of sphingolipids in the formation of lipid rafts in podocytes and their
contribution to the maintenance of a functional slit diaphragm in the glomerulus
will be discussed.
PMID- 25126093
TI - Molecular targets of chromatin repressive mark H3K9me3 in primate progenitor
cells within adult neurogenic niches.
AB - Histone 3 Lysine 9 (H3K9) methylation is known to be associated with pericentric
heterochromatin and important in genomic stability. In this study, we show that
trimethylation at H3K9 (H3K9me3) is enriched in an adult neural stem cell niche-
the subventricular zone (SVZ) on the walls of the lateral ventricle in both
rodent and non-human primate baboon brain. Previous studies have shown that there
is significant correlation between baboon and human regarding genomic similarity
and brain structure, suggesting that findings in baboon are relevant to human. To
understand the function of H3K9me3 in this adult neurogenic niche, we performed
genome-wide analyses using ChIP-Seq (chromatin immunoprecipitation and deep
sequencing) and RNA-Seq for in vivo SVZ cells purified from baboon brain. Through
integrated analyses of ChIP-Seq and RNA-Seq, we found that H3K9me3-enriched genes
associated with cellular maintenance, post-transcriptional and translational
modifications, signaling pathways, and DNA replication are expressed, while genes
involved in axon/neuron, hepatic stellate cell, or immune-response activation are
not expressed. As neurogenesis progresses in the adult SVZ, cell fate restriction
is essential to direct proper lineage commitment. Our findings highlight that
H3K9me3 repression in undifferentiated SVZ cells is engaged in the maintenance of
cell type integrity, implicating a role for H3K9me3 as an epigenetic mechanism to
control cell fate transition within this adult germinal niche.
PMID- 25126094
TI - Does the Implant Surgical Technique Affect the Primary and/or Secondary Stability
of Dental Implants? A Systematic Review.
AB - Background. A number of surgical techniques for implant site preparation have
been advocated to enhance the implant of primary and secondary stability.
However, there is insufficient scientific evidence to support the association
between the surgical technique and implant stability. Purpose. This review aimed
to investigate the influence of different surgical techniques including the
undersized drilling, the osteotome, the piezosurgery, the flapless procedure, and
the bone stimulation by low-level laser therapy on the primary and/or secondary
stability of dental implants. Materials and methods. A search of PubMed, Cochrane
Library, and grey literature was performed. The inclusion criteria comprised
observational clinical studies and randomized controlled trials (RCTs) conducted
in patients who received dental implants for rehabilitation, studies that
evaluated the association between the surgical technique and the implant primary
and/or secondary stability. The articles selected were carefully read and
classified as low, moderate, and high methodological quality and data of interest
were tabulated. Results. Eight clinical studies were included then they were
classified as moderate or high methodological quality and control of bias.
Conclusions. There is a weak evidence suggesting that any of previously mentioned
surgical techniques could influence the primary and/or secondary implant
stability.
PMID- 25126095
TI - Successful management of coronary artery rupture with stent-graft: a case report.
AB - Perforation of coronary arteries is a relatively rare yet life-threatening
complication of percutaneus coronary interventions and is encountered in
approximately 0.5% of these procedures. According to the type of coronary
perforation, various methods of correction are employed, ranging from
conservative approach to emergency cardiac surgery. Coronary stent-grafts are
composed of two metal stents and a polytetrafluoroethylene layer between them.
Advent of such stents enabled efficient endovascular repair of coronary artery
perforation. We present a case of coronary artery perforation which had occurred
during stent implantation for the treatment of a bridged segment in the distal
portion of the left anterior descending artery. This perforation was successfully
managed by implanting a stent-graft.
PMID- 25126096
TI - Acute abdominal pain after intercourse: adrenal hemorrhage as the first sign of
metastatic lung cancer.
AB - Although the adrenal glands are a common site of cancer metastases, they are
often asymptomatic and discovered incidentally on CT scan or autopsy. Spontaneous
adrenal hemorrhage associated with metastatic lung cancer is an exceedingly rare
phenomenon, and diagnosis can be difficult due to its nonspecific symptoms and
ability to mimic other intra-abdominal pathologies. We report a case of a 65-year
old man with a history of right upper lobectomy seven months earlier for stage IB
non-small cell lung cancer who presented with acute abdominal pain after
intercourse. CT scan revealed a new right adrenal mass with surrounding
hemorrhage, and subsequent FDG-PET scan confirmed new metabolic adrenal
metastases. The patient's presentation of abdominal pain and adrenal hemorrhage
immediately after sexual intercourse suggests that exertion, straining, or
increased intra-abdominal pressure might be risk factors for precipitation of
hemorrhage in patients with adrenal metastases. Management includes pain control
and supportive treatment in mild cases, with arterial embolization or
adrenalectomy being reserved for cases of severe hemorrhage.
PMID- 25126092
TI - Unraveling plant hormone signaling through the use of small molecules.
AB - Plants have acquired the capacity to grow continuously and adjust their
morphology in response to endogenous and external signals, leading to a high
architectural plasticity. The dynamic and differential distribution of
phytohormones is an essential factor in these developmental changes. Phytohormone
perception is a fast but complex process modulating specific developmental
reprogramming. In recent years, chemical genomics or the use of small molecules
to modulate target protein function has emerged as a powerful strategy to study
complex biological processes in plants such as hormone signaling. Small molecules
can be applied in a conditional, dose-dependent and reversible manner, with the
advantage of circumventing the limitations of lethality and functional redundancy
inherent to traditional mutant screens. High-throughput screening of diverse
chemical libraries has led to the identification of bioactive molecules able to
induce plant hormone-related phenotypes. Characterization of the cognate targets
and pathways of those molecules has allowed the identification of novel
regulatory components, providing new insights into the molecular mechanisms of
plant hormone signaling. An extensive structure-activity relationship (SAR)
analysis of the natural phytohormones, their designed synthetic analogs and newly
identified bioactive molecules has led to the determination of the structural
requirements essential for their bioactivity. In this review, we will summarize
the so far identified small molecules and their structural variants targeting
specific phytohormone signaling pathways. We will highlight how the SAR analyses
have enabled better interrogation of the molecular mechanisms of phytohormone
responses. Finally, we will discuss how labeled/tagged hormone analogs can be
exploited, as compelling tools to better understand hormone signaling and
transport mechanisms.
PMID- 25126097
TI - One-year prevalence, comorbidities and cost of cachexia-related inpatient
admissions in the USA.
AB - BACKGROUND: Cachexia is a condition characterized as a loss in body mass or
metabolic dysfunction and is associated with several prevalent chronic health
conditions including many cancers, COPD, HIV, and kidney disease, with between 10
and 50% of patients with these conditions having cachexia. Currently there is
little research into cachexia and our objective is to characterize cachexia
patients, their healthcare utilization, and associated hospitalization costs.
Given the increasing prevalence of chronic diseases, it is important to better
understand cachexia so that the condition can be better diagnosed and managed.
METHODS: We utilized one year (2009) of the Nationwide Inpatient Sample (NIS).
The NIS represents all inpatient stays at a random 20% sample of all hospitals
within the United States. We grouped cachexia individuals by primary or secondary
discharge diagnosis and then compared those with cachexia to all others in terms
of length of stay (LOS) and total cost. Finally we looked into factors predicting
increased LOS using a negative binomial model. RESULTS: We estimated US
prevalence for cachexia-related inpatient admissions at 161,898 cases. Cachexia
patients were older, with an average age of 67.95 versus 48.10 years in their non
cachexia peers. Hospitalizations associated with cachexia had an increased LOS
compared to non-cachexia patients (6 versus 3 days), with average costs per stay
$4641.30 greater. Differences were seen in loss of function (LOF) with cachexia
patients, mostly in the major LOF category (52.60%), whereas non-cachexia
patients were spread between minor, moderate, and major LOF (36.28%, 36.11%, and
21.26%, respectively). Significant positive predictors of increased LOS among
cachexia patients included urban hospital (IRR=1.21, non-teaching urban;
IRR=1.23, teaching urban), having either major (IRR=1.41) or extreme (IRR=2.64)
LOF, and having a primary diagnosis of pneumonia (IRR=1.15). CONCLUSION: We have
characterized cachexia and seen it associated with increased length of stay,
increased cost, and more severe loss of function in patients compared to those
without cachexia.
PMID- 25126098
TI - Retrospective long-term comparison of naturopathic fasting therapy and weight
reduction diet in overweight patients.
AB - In a follow-up study overweight and obese patients fasting according to Buchinger
(modified) and a control group treated by a weight reduction diet in the context
of an inpatient naturopathic complex treatment were compared using a
questionnaire developed for a standardized phone interview 6.8 +/- 1.1 years
after inpatient treatment. During the inpatient treatment the fasting patients
significantly more body weight, but at the time of the interview significantly
more weight was gained again. 10.7% of the fasting patients and 31.9% of the
control group lowered their weight at least 5% of their initial weight up to the
interview. 42% of the fasting and 74% of the control group persistently changed
their diet. The control group followed a significantly higher number of trained
nutritional aspects. 21% of the fasting and 40% of the control group increased
their leisure activity permanently. Continued improvement in quality of life was
achieved by 16% of the fasting patients and 28% of the control group. The fasting
therapy, carried out as part of the inpatient naturopathic complex treatment,
turned out to be less suitable for the treatment of overweight and obesity
compared to standard therapy. One likely determinant is the minor poststationary
lifestyle modification.
PMID- 25126100
TI - Buyang huanwu decoction for healthcare: evidence-based theoretical
interpretations of treating different diseases with the same method and target of
vascularity.
AB - Buyang Huanwu Decoction (BHD) is a famous herbal prescription that has been used
to treat stroke for centuries. Recent studies reported that the use of BHD had
been extended to treat various kinds of disorders according to the TCM syndrome
theory of Treating Different Diseases with the Same Method (TDDSM). Here, an
overview of systematic reviews (SRs) of BHD for healthcare was conducted to
interpret the TCM theory of TDDSM and its target of vascularity in an evidence
based manner. Literature searches were carried out in 5 databases to search SRs
of BHD for any indication up to August 2013. Thirteen eligible SRs were
identified which reported a wide range of vascular conditions. Based on the
Overview Quality Assessment Questionnaire scores, the quality of included SRs was
varied, with an average score of 4 points. We found that there is premature
evidence for the use of BHD for healthcare, whereas BHD was well tolerable in all
patients. BHD can be used to treat many disorders with the same therapeutic
principle of invigorating Qi to activate blood circulation, which is essentially
a manifestation of the TDDSM and is likely to account for targeting the specific
pathogenesis of vascular diseases.
PMID- 25126101
TI - A unique electrical thermal stimulation system comparable to moxibustion of
subcutaneous tissue.
AB - Moxibustion strengthens immunity and it is an effective treatment modality, but,
depending on the material quantity, shape, and composition, the thermal strength
and intensity can be difficult to control, which may cause pain or epidermal
burns. To overcome these limitations, a heat stimulating system which is able to
control the thermal intensity was developed. The temperature distributions on
epidermis, at 5 mm and 10 mm of depth, in rabbit femoral tissue were compared
between moxibustion and the electric thermal stimulation system. The stimulation
system consists of a high radio frequency dielectric heating equipment (2 MHz
frequency, maximum power 200 W), isolation probe, isolation plate, negative
pressure generator, and a temperature assessment system. The temperature was
modulated by controlling the stimulation pulse duty ratio, repetition number, and
output. There were 95% and 91% temperature distribution correlations between
moxibustion and the thermal stimulus at 5 mm and 10 mm of depth in tissue,
respectively. Moreover, the epidermal temperature in thermal stimulation was
lower than that in moxibustion. These results showed that heat loss by the
electric thermal stimulation system is less than that by the traditional
moxibustion method. Furthermore, the proposed electric thermal stimulation did
not cause adverse effects, such as suppuration or blisters, and also provided
subcutaneous stimulation comparable to moxibustion.
PMID- 25126099
TI - Antileishmanial activity of medicinal plants used in endemic areas in
northeastern Brazil.
AB - This study investigates the leishmanicidal activity of five species of plants
used in folk medicine in endemic areas of the state of Alagoas, Brazil. Data were
collected in the cities of Colonia Leopoldina, Novo Lino, and Uniao dos Palmares,
Alagoas state, from patients with cutaneous leishmaniasis (Leishmania
amazonensis) who use medicinal plants to treat this disease. Plants extracts were
tested at a concentration of 1-100 MUg/mL in all experiments, except in an assay
to evaluate activity against amastigotes, when 10 MUg/mL was used. All plants
extracts did not show deleterious activity to the host cell evidenced by LDH
assay at 100, 10, and 1 MUg/mL after 48 h of incubation. The plants extracts
Hyptis pectinata (L.) Poit, Aloe vera L., Ruta graveolens L., Pfaffia glomerata
(Spreng.) Pedersen, and Chenopodium ambrosioides L. exhibited direct activity
against extracellular forms at 100 MUg/mL; these extracts inhibited growth by
81.9%, 82.9%, 74.4%, 88.7%, and 87.4%, respectively, when compared with
promastigotes. The plants extracts H. pectinata, A. vera, and R. graveolens also
significantly diminished the number of amastigotes at 10 MUg/mL, inhibiting
growth by 85.0%, 40.4%, 94.2%, and 97.4%, respectively, when compared with
control. Based on these data, we conclude that the five plants exhibited
considerable leishmanicidal activity.
PMID- 25126102
TI - Neurotrophic Signaling Factors in Brain Ischemia/Reperfusion Rats: Differential
Modulation Pattern between Single-Time and Multiple Electroacupuncture
Stimulation.
AB - Electroacupuncture (EA) treatment has been widely used for stroke-like disorders
in traditional Chinese medicine. However, the underlying mechanisms remain
unclear. Our previous studies showed that single-time EA stimulation at "Baihui"
(GV 20) and "Shuigou" (GV 26) after the onset of ischemia can protect the brain
against ischemic injury in rats with middle cerebral artery occlusion (MCAO).
Here, we further investigated the differential effects between multiple EA and
single-time EA stimulation on ischemic injury. In the present study, we found
that both single-time EA and multiple EA stimulation significantly reduced MCAO
induced ischemic infarction, while only multiple EA attenuated sensorimotor
dysfunctions. Also, with PCR array screening and ingenuity gene analysis, we
revealed that multiple EA and single-time EA stimulation could differentially
induce expression changes in neurotrophic signaling related genes. Meanwhile,
with western blotting, we demonstrated that the level of glia maturation factor
beta (GMFbeta) increased in the early stage (day 1) of reperfusion, and this
upregulation was suppressed only by single-time EA stimulation. These findings
suggest that the short-term effect of single-time EA stimulation differs from the
cumulative effect of multiple EA, which possibly depends on their differential
modulation on neurotrophic signaling molecules expression.
PMID- 25126103
TI - A novel nonparametric item response theory approach to measuring socioeconomic
position: a comparison using household expenditure data from a Vietnam health
survey, 2003.
AB - BACKGROUND: Measures of household socio-economic position (SEP) are widely used
in health research. There exist a number of approaches to their measurement, with
Principal Components Analysis (PCA) applied to a basket of household assets being
one of the most common. PCA, however, carries a number of assumptions about the
distribution of the data which may be untenable, and alternative, non-parametric,
approaches may be preferred. Mokken scale analysis is a non-parametric, item
response theory approach to scale development which appears never to have been
applied to household asset data. A Mokken scale can be used to rank order items
(measures of wealth) as well as households. Using data on household asset
ownership from a national sample of 4,154 consenting households in the World
Health Survey from Vietnam, 2003, we construct two measures of household SEP.
Seventeen items asking about assets, and utility and infrastructure use were
used. Mokken Scaling and PCA were applied to the data. A single item measure of
total household expenditure is used as a point of contrast. RESULTS: An 11 item
scale, out of the 17 items, was identified that conformed to the assumptions of a
Mokken Scale. All the items in the scale were identified as strong items (Hi >
.5). Two PCA measures of SEP were developed as a point of contrast. One PCA
measure was developed using all 17 available asset items, the other used the
reduced set of 11 items identified in the Mokken scale analaysis. The Mokken
Scale measure of SEP and the 17 item PCA measure had a very high correlation (r =
.98), and they both correlated moderately with total household expenditure: r =
.59 and r = .57 respectively. In contrast the 11 item PCA measure correlated
moderately with the Mokken scale (r = .68), and weakly with the total household
expenditure (r = .18). CONCLUSION: The Mokken scale measure of household SEP
performed at least as well as PCA, and outperformed the PCA measure developed
with the 11 items used in the Mokken scale. Unlike PCA, Mokken scaling carries no
assumptions about the underlying shape of the distribution of the data, and can
be used simultaneous to order household SEP and items. The approach, however, has
not been tested with data from other countries and remains an interesting, but
under researched approach.
PMID- 25126104
TI - Returning findings within longitudinal cohort studies: the 1958 birth cohort as
an exemplar.
AB - Population-based, prospective longitudinal cohort studies are considering the
issues surrounding returning findings to individuals as a result of genomic and
other medical research studies. While guidance is being developed for clinical
settings, the process is less clear for those conducting longitudinal research.
This paper discusses work conducted on behalf of The UK Cohort and Longitudinal
Study Enhancement Resource programme (CLOSER) to examine consent requirements,
process considerations and specific examples of potential findings in the context
of the 1958 British Birth cohort. Beyond deciding which findings to return, there
are questions of whether re-consent is needed and the possible impact on the
study, how the feedback process will be managed, and what resources are needed to
support that process. Recommendations are made for actions a cohort study should
consider taking when making vital decisions regarding returning findings. Any
decisions need to be context-specific, arrived at transparently, communicated
clearly, and in the best interests of both the participants and the study.
PMID- 25126105
TI - From spatial ecology to spatial epidemiology: modeling spatial distributions of
different cancer types with principal coordinates of neighbor matrices.
AB - BACKGROUND: Epidemiology and ecology share many fundamental research questions.
Here we describe how principal coordinates of neighbor matrices (PCNM), a method
from spatial ecology, can be applied to spatial epidemiology. PCNM is based on
geographical distances among sites and can be applied to any set of sites
providing a good coverage of a study area. In the present study, PCNM
eigenvectors corresponding to positive autocorrelation were used as explanatory
variables in linear regressions to model incidences of eight most common cancer
types in Finnish municipalities (n = 320). The dataset was provided by the
Finnish Cancer Registry and it included altogether 615,839 cases between 1953 and
2010. RESULTS: PCNM resulted in 165 vectors with a positive eigenvalue. The first
PCNM vector corresponded to the wavelength of hundreds of kilometers as it
contrasted two main subareas so that municipalities located in southwestern
Finland had the highest positive site scores and those located in midwestern
Finland had the highest negative scores in that vector. Correspondingly, the
165(th) PCNM vector indicated variation mainly between the two small
municipalities located in South Finland. The vectors explained 13 - 58% of the
spatial variation in cancer incidences. The number of outliers having
standardized residual > |3| was very low, one to six per model, and even lower,
zero to two per model, according to Chauvenet's criterion. The spatial variation
of prostate cancer was best captured (adjusted r (2) = 0.579). CONCLUSIONS: PCNM
can act as a complementary method to causal modeling to achieve a better
understanding of the spatial structure of both the response and explanatory
variables, and to assess the spatial importance of unmeasured explanatory
factors. PCNM vectors can be used as proxies for demographics and causative
agents to deal with autocorrelation, multicollinearity, and confounding
variables. PCNM may help to extend spatial epidemiology to areas with limited
availability of registers, improve cost-effectiveness, and aid in identifying
unknown causative agents, and predict future trends in disease distributions and
incidences. A large advantage of using PCNM is that it can create statistically
valid reflectors of real predictors for disease incidence models with only little
resources and background information.
PMID- 25126106
TI - Duplication of the NPHP1 gene in patients with autism spectrum disorder and
normal intellectual ability: a case series.
AB - Autism spectrum disorder is a neurodevelopmental disorder characterized by
impairments in social interactions, reduced verbal communication abilities,
stereotyped repetitive behaviors, and restricted interests. It is a complex
condition caused by genetic and environmental factors; the high heritability of
this disorder supports the presence of a significant genetic contribution. Many
studies have suggested that copy-number variants contribute to the etiology of
autism spectrum disorder. Recently, copy-number variants of the nephronophthisis
1 gene have been reported in patients with autism spectrum disorder. To the best
of our knowledge, only six autism spectrum disorder cases with duplications of
the nephronophthisis 1 gene have been reported. These patients exhibited
intellectual dysfunction, including verbal dysfunction in one patient, below
average verbal intellectual ability in one patient, and intellectual disability
in four patients. In this study, we identified nephronophthisis 1 duplications in
two unrelated Japanese patients with autism spectrum disorder using a high
resolution single-nucleotide polymorphism array. This report is the first to
describe a nephronophthisis 1 duplication in an autism spectrum disorder patient
with an average verbal intelligence quotient and an average performance
intelligence quotient. However, the second autism spectrum disorder patient with
a nephronophthisis 1 duplication had a below-average performance intelligence
quotient. Neither patient exhibited physical dysfunction, motor developmental
delay, or neurological abnormalities. This study supports the clinical
observation of nephronophthisis 1 duplication in autism spectrum disorder cases
and might contribute to our understanding of the clinical phenotype that arises
from this duplication.
PMID- 25126107
TI - Privacy-preserving self-helped medical diagnosis scheme based on secure two-party
computation in wireless sensor networks.
AB - With the continuing growth of wireless sensor networks in pervasive medical care,
people pay more and more attention to privacy in medical monitoring, diagnosis,
treatment, and patient care. On one hand, we expect the public health
institutions to provide us with better service. On the other hand, we would not
like to leak our personal health information to them. In order to balance this
contradiction, in this paper we design a privacy-preserving self-helped medical
diagnosis scheme based on secure two-party computation in wireless sensor
networks so that patients can privately diagnose themselves by inputting a health
card into a self-helped medical diagnosis ATM to obtain a diagnostic report just
like drawing money from a bank ATM without revealing patients' health information
and doctors' diagnostic skill. It makes secure self-helped disease diagnosis
feasible and greatly benefits patients as well as relieving the heavy pressure of
public health institutions.
PMID- 25126108
TI - Automatic blastomere recognition from a single embryo image.
AB - The number of blastomeres of human day 3 embryos is one of the most important
criteria for evaluating embryo viability. However, due to the transparency and
overlap of blastomeres, it is a challenge to recognize blastomeres automatically
using a single embryo image. This study proposes an approach based on least
square curve fitting (LSCF) for automatic blastomere recognition from a single
image. First, combining edge detection, deletion of multiple connected points,
and dilation and erosion, an effective preprocessing method was designed to
obtain part of blastomere edges that were singly connected. Next, an automatic
recognition method for blastomeres was proposed using least square circle
fitting. This algorithm was tested on 381 embryo microscopic images obtained from
the eight-cell period, and the results were compared with those provided by
experts. Embryos were recognized with a 0 error rate occupancy of 21.59%, and the
ratio of embryos in which the false recognition number was less than or equal to
2 was 83.16%. This experiment demonstrated that our method could efficiently and
rapidly recognize the number of blastomeres from a single embryo image without
the need to reconstruct the three-dimensional model of the blastomeres first;
this method is simple and efficient.
PMID- 25126109
TI - Computational and control methods in rehabilitation medicine.
PMID- 25126111
TI - Mathematical modelling of cerebral blood circulation and cerebral autoregulation:
towards preventing intracranial hemorrhages in preterm newborns.
AB - Impaired cerebral autoregulation leads to fluctuations in cerebral blood flow,
which can be especially dangerous for immature brain of preterm newborns. In this
paper, two mathematical models of cerebral autoregulation are discussed. The
first one is an enhancement of a vascular model proposed by Piechnik et al. We
extend this model by adding a polynomial dependence of the vascular radius on the
arterial blood pressure and adjusting the polynomial coefficients to experimental
data to gain the autoregulation behavior. Moreover, the inclusion of a Preisach
hysteresis operator, simulating a hysteretic dependence of the cerebral blood
flow on the arterial pressure, is tested. The second model couples the blood
vessel system model by Piechnik et al. with an ordinary differential equation
model of cerebral autoregulation by Ursino and Lodi. An optimal control setting
is proposed for a simplified variant of this coupled model. The objective of the
control is the maintenance of the autoregulatory function for a wider range of
the arterial pressure. The control can be interpreted as the effect of a
medicament changing the cerebral blood flow by, for example, dilation of blood
vessels. Advanced numerical methods developed by the authors are applied for the
numerical treatment of the control problem.
PMID- 25126110
TI - ProBLM web server: protein and membrane placement and orientation package.
AB - The 3D structures of membrane proteins are typically determined without the
presence of a lipid bilayer. For the purpose of studying the role of membranes on
the wild type characteristics of the corresponding protein, determining the
position and orientation of transmembrane proteins within a membrane environment
is highly desirable. Here we report a geometry-based approach to automatically
insert a membrane protein with a known 3D structure into pregenerated lipid
bilayer membranes with various dimensions and lipid compositions or into a
pseudomembrane. The pseudomembrane is built using the Protein Nano-Object
Integrator which generates a parallelepiped of user-specified dimensions made up
of pseudoatoms. The pseudomembrane allows for modeling the desolvation effects
while avoiding plausible errors associated with wrongly assigned protein-lipid
contacts. The method is implemented into a web server, the ProBLM server, which
is freely available to the biophysical community. The web server allows the user
to upload a protein coordinate file and any missing residues or heavy atoms are
regenerated. ProBLM then creates a combined protein-membrane complex from the
given membrane protein and bilayer lipid membrane or pseudomembrane. The user is
given an option to manually refine the model by manipulating the position and
orientation of the protein with respect to the membrane.
PMID- 25126112
TI - Challenges in predicting the evolutionary maintenance of a phage transgene.
AB - BACKGROUND: In prior work, a phage engineered with a biofilm-degrading enzyme
(dispersin B) cleared artificial, short-term biofilms more fully than the phage
lacking the enzyme. An unresolved question is whether the transgene will be lost
or maintained during phage growth - its loss would limit the utility of the
engineering. Broadly supported evolutionary theory suggests that transgenes will
be lost through a 'tragedy of the commons' mechanism unless the ecology of growth
in biofilms meets specific requirements. We test that theory here. RESULTS:
Functional properties of the transgenic phage were identified. Consistent with
the previous study, the dispersin phage was superior to unmodified phage at
clearing short term biofilms grown in broth, shown here to be an effect
attributable to free enzyme. However, the dispersin phage was only marginally
better than control phages on short term biofilms in minimal media and was no
better than control phages in clearing long term biofilms. There was little
empirical support for the tragedy of the commons framework despite a strong
theoretical foundation for its supposed relevance. The framework requires that
the transgene imposes an intrinsic cost, yet the transgene was intrinsically
neutral or beneficial when expressed from one part of the phage genome. Expressed
from a different part of the genome, the transgene did behave as if intrinsically
costly, but its maintenance did not benefit from spatially structured growth per
se - violating the tragedy framework. CONCLUSIONS: Overall, the transgene was
beneficial under many conditions, but no insight to its maintenance was
attributable to the established evolutionary framework. The failure likely
resides in system details that would be used to parameterize the models. Our
study cautions against naive applications of evolutionary theory to synthetic
biology, even qualitatively.
PMID- 25126113
TI - Minireactor-based high-throughput temperature profiling for the optimization of
microbial and enzymatic processes.
AB - BACKGROUND: Bioprocesses depend on a number of different operating parameters and
temperature is one of the most important ones. Unfortunately, systems for rapid
determination of temperature dependent reaction kinetics are rare. Obviously,
there is a need for a high-throughput screening procedure of temperature
dependent process behavior. Even though, well equipped micro-bioreactors are a
promising approach sufficient temperature control is quite challenging and rather
complex. RESULTS: In this work a unique system is presented combining an optical
on-line monitoring device with a customized temperature control unit for 96 well
microtiter plates. By exposing microtiter plates to specific temperature
profiles, high-throughput temperature optimization for microbial and enzymatic
systems in a micro-scale of 200 MUL is realized. For single well resolved
temperature measurement fluorescence thermometry was used, combining the
fluorescent dyes Rhodamin B and Rhodamin 110. The real time monitoring of the
microbial and enzymatic reactions provides extensive data output. To evaluate
this novel system the temperature optima for Escherichia coli and Kluyveromyces
lactis regarding growth and recombinant protein production were determined.
Furthermore, the commercial cellulase mixture Celluclast as a representative for
enzymes was investigated applying a fluorescent activity assay. CONCLUSION:
Microtiter plate-based high-throughput temperature profiling is a convenient tool
for characterizing temperature dependent reaction processes. It allows the
evaluation of numerous conditions, e.g. microorganisms, enzymes, media, and
others, in a short time. The simple temperature control combined with a
commercial on-line monitoring device makes it a user friendly system.
PMID- 25126114
TI - A new patient with a terminal de novo 2p25.3 deletion of 1.9 Mb associated with
early-onset of obesity, intellectual disabilities and hyperkinetic disorder.
AB - Terminal and interstitial deletions of 2p25.3 (size < Mb), detected by array-CGH
analysis, have been reported in about 18 patients sharing common clinical
features represented by early-onset obesity/ overweightness associated with
intellectual disabilities (ID) and behavioural troubles. This observations led to
hypothesize that 2p subtelomeric deletion should be associated with syndromic
obesity and MYT1L became the main candidate gene for ID and obesity since it is
deleted or disrupted in all hitherto published cases. Here we described a 2p25.3
de novo terminal deletion of 1.9 Mb, of paternal origin, detected by array-CGH
analysis in a girl of 4.4 years with a distinctive phenotype consisting of early
onset of obesity associated with moderate ID, and hyperkinetic disorder. The
deletion disrupted MYT1L and encompassed five other OMIM genes, ACP1, TMEM18,
SNTG2, TPO, and PXDN. Here, we discuss the combined functional effects of
additional haploinsufficient genes, that may concur with heterozygous deletion of
MYT1L, in the aetiology for syndromic obesity associated with 2p25.5 subtelomeric
deletion.
PMID- 25126115
TI - Association between Brachial-Ankle pulse wave velocity and cardiac autonomic
neuropathy in type 2 diabetes.
AB - BACKGROUND: Cardiac autonomic neuropathy (CAN) is a common complication of type 2
diabetes mellitus (T2DM). Brachial-ankle pulse wave velocity (baPWV) is known to
be a good surrogate marker of vascular damages. The goal of this study was to
investigate the relationship between BaPWV and CAN in T2DM. METHODS: A total of
148 patients who had no apparent history of cardiovascular condition were
enrolled consecutively in this study. The correlation between increased baPWV and
CAN was analyzed. CAN was evaluated by five standard cardiovascular reflex tests
(CARTs) according to the Ewing's protocol: 1) heart rate variation during deep
breathing, 2) heart rate response to standing, 3) Valsalva maneuver, 4) postural
systolic blood pressure (BP) change, 5) Sustained handgrip test. CAN was defined
as the presence of at least two abnormal tests. RESULTS: The mean age of patients
was 59.8 +/- 7.8 years. The mean duration of diabetes was 6.0(2.0-11.0) years.
The mean baPWV was 1665.5(1482.0-1940.0) cm/sec. Subjects with CAN were older and
had high BMI, baPWV compared with those without CAN. The proportion of patients
with diabetic peripheral neuropathy was higher in subjects with CAN. After
adjusting for other confounding risk factors, baPWV (odds ratio = 8.496, 95% CI:
1.216-59.348; P = 0.031) remained as independent risk factors for CAN. The number
of abnormal CARTs increased gradually with increasing baPWV (correlation
coefficient =0.255, p = 0.002). CONCLUSION: Increased baPWV was significantly
correlated with CAN in patients with type 2 diabetes.
PMID- 25126119
TI - Cerebral aspergilloma in a SLE patient: A case report with short literature
review.
AB - Aspergillosis of brain is very rare, and commonly seen in immunocompromised or
immunosuppressed patient. Here, we report a cerebral aspergillosis condition in a
late teen girl who is a Systemic Lupus Erythromatosis patient with steroid
therapy. She developed headaches, vomitings, and convulsions. On the basis of
clinical and neuroimaging, a diagnosis of cerebral tuberculoma was made, and she
was put on anti-TB therapy, but she did not respond. Later, surgical partial
excision biopsy confirmed the diagnosis. Her cerebral lesions responded with
antifungal itraconazole therapy. The case will be presented with short literature
review. Such a report in the literature is rare.
PMID- 25126118
TI - Complication avoidance in transcallosal transforaminal approach to colloid cysts
of the anterior third ventriclen: An analysis of 80 cases.
AB - OBJECT: The objective of the present study is to analyze the complications and
their avoidance in a series of 80 patients operated by transcallosal
transforaminal approach to colloid cysts of the anterior third ventricle.
MATERIALS AND METHODS: The surgical outcome and complications of 80 patients
operated by transcallosal transforaminal approach for colloid cysts in the
anterior third ventricle was analyzed. A detailed pre- and post-operative
neurological assessment was done in all patients. Neurocognitive assessment of
corpus callosal function was done in the last 22 cases. CT scan of the brain was
done in all patients, before and after surgery. RESULTS: All patients underwent
transcallosal transforaminal approach. Total excision of the lesion was achieved
in 79 patients and subtotal in one. The complications encountered were
postoperative seizures in six, acute hydrocephalus in four, venous cortical
infarct in four, transient hemiparesis in four, transient memory impairment,
especially for immediate recall in nine, mutism in one, subdural hematoma in one,
meningitis in three, and tension pneumocephalus in one patient. There were two
mortalities. There was no incidence of postoperative disconnection syndrome.
CONCLUSION: Colloid cyst is surgically curable. With good knowledge of the
regional anatomy and meticulous microsurgical techniques, there is a low
mortality and minimum morbidity, when compared to the natural history of the
disease. With increasing experience, most of the complications are avoidable. The
limited anterior callosotomy does not result in disconnection syndromes.
PMID- 25126116
TI - piRNA clusters and open chromatin structure.
AB - Transposable elements (TEs) are major structural components of eukaryotic
genomes; however, mobilization of TEs generally has negative effects on the host
genome. To counteract this threat, host cells have evolved genetic and epigenetic
mechanisms that keep TEs silenced. One such mechanism involves the Piwi-piRNA
complex, which represses TEs in animal gonads either by cleaving TE transcripts
in the cytoplasm or by directing specific chromatin modifications at TE loci in
the nucleus. Most Piwi-interacting RNAs (piRNAs) are derived from genomic piRNA
clusters. There has been remarkable progress in our understanding of the
mechanisms underlying piRNA biogenesis. However, little is known about how a
specific locus in the genome is converted into a piRNA-producing site. In this
review, we will discuss a possible link between chromatin boundaries and piRNA
cluster formation.
PMID- 25126120
TI - Impact of clinico-radiological parameters on the outcome of treatment in brain
tuberculosis.
AB - OBJECTIVES: The Aim of this study was to evaluate the impact of clinico
radiological parameters on the outcome of the treatment in brain tuberculosis.
MATERIALS AND METHODS: This study was conducted in the Department of Neurosurgery
and Neurology Skims Srinagar India for a period of two years from November 2009
to November 2011. A total of 61 patients presenting with brain tuberculosis
admitted at skims during these two years were included in the study. Patients
having clinical, laboratory and radiological findings suggestive of brain
tuberculosis were included in the study. On correlating the CT characteristics
tuberculomas, basal exudates and hydrocephalus with sequelae at 6,12 and 18
months - focal deficit, cognitive impairment, and diplopia. RESULTS: It was seen
that basal exudates correlated with all the three neurological sequelae i.e.;
with focal deficit (P = 0.001), cognitive impairment (P = 0.011), and diplopia (P
= 0.021). Hydrocephalus correlated well with cognitive impairment (P = 0.031) and
tuberculoma correlated with none of these clinical characteristics. CONCLUSION:
We concluded that the mortality and neurologic sequelae were directly related to
the clinical stage of disease at presentation. Correlating the CT characteristics
we concluded that basal exudates correlated with all the three sequelae i.e.;
with focal deficit, cognitive impairment, and diplopia. Hydrocephalous correlated
well with cognitive impairment and tuberculoma correlated with none of these
clinical characteristics.
PMID- 25126121
TI - Spinal dysraphism: A challenge continued to be faced by neurosurgeons in
developing countries.
AB - OBJECTIVES: The incidence of spinal dysraphism has significantly decreased over
the last few decades, all over the world; however, still the incidence is much
higher in developing countries with poor socioeconomic status. MATERIALS AND
METHODS: The present study includes all patients managed for spinal dysraphism
over a period of one year (January 2011-December 2011). Details including
demographics, antenatal care history, site and type of lesion, neurological
examination, imaging finding, associated congenital anomalies, management
offered, and outcome were recorded. RESULTS: A total of 27 children were operated
for spinal dysraphism during the study period (17 males and 11 females). Median
age was 120 days (age range, 1 day to 6 years). Mothers of 15 children did not
seek any regular antenatal checkup and only 13 mothers received folic acid
supplementation during pregnancy. Fourteen children were delivered at home and 13
were at hospital. The most common site was lumbosacral region (67.8%). Seven
patients had rupture of the sac at the time of presentation, one child had local
infection, and four patients had hydrocephalus (requiring shunt before surgical
repair). Two patients developed hydrocephalus at follow up, needing shunt
surgery. The mean hospital stay was 7 days (range, 5 days to 31 days; median, 10
days). CONCLUSION: Spinal dysraphism is still a major public health problem in
developing countries. Management of patients with spinal dysraphism is complex
and needs close coordination between pediatrician, neurologist, neurosurgeon, and
rehabilitation experts. A large number of factors influence the outcome.
PMID- 25126117
TI - Recent advances in the analysis of therapeutic proteins by capillary and
microchip electrophoresis.
AB - The development of therapeutic proteins and peptides is an expensive and time
intensive process. Biologics, which have become a multi-billion dollar industry,
are chemically complex products that require constant observation during each
stage of development and production. Post-translational modifications along with
chemical and physical degradation from oxidation, deamidation, and aggregation,
lead to high levels of heterogeneity that affect drug quality and efficacy. The
various separation modes of capillary electrophoresis (CE) are commonly utilized
to perform quality control and assess protein heterogeneity. This review attempts
to highlight the most recent developments and applications of CE separation
techniques for the characterization of protein and peptide therapeutics by
focusing on papers accepted for publication in the in the two-year period between
January 2012 and December 2013. The separation principles and technological
advances of CE, capillary gel electrophoresis, capillary isoelectric focusing,
capillary electrochromatography and CE-mass spectrometry are discussed, along
with exciting new applications of these techniques to relevant pharmaceutical
issues. Also included is a small selection of papers on microchip electrophoresis
to show the direction this field is moving with regards to the development of
inexpensive and portable analysis systems for on-site, high-throughput analysis.
PMID- 25126122
TI - Ventriculoperitoneal shunting: Laparoscopically assisted versus conventional open
surgical approaches.
AB - OBJECTIVES: Ventriculoperitoneal shunting (VPS) is a mainstay of hydrocephalus
therapy, but carries a significant risk of device malfunctioning. This study aims
to compare the outcomes of laparoscopic ventriculoperitoneal shunting versus open
ventriculoperitoneal shunting (OVPS) VPS-placement and reviews our findings in
the pertinent context of the literature from 1993 to 2012. MATERIALS AND METHODS:
Between 2003 and 2012, a total of 232 patients underwent first time VPS placement
at Beth Israel Deaconess Medical Center. Of those, 155 were laparoscopically
guided and 77 were done conventionally. We analyzed independent variables (age,
gender, medical history, clinical presentation, indication for surgery and
surgical technique) and dependent variables (operative time, post-operative
complications, length of stay in the hospital) and occurrence of shunt failure.
RESULTS: Mean operative time was 43.7 min (18.0-102.0) in the laparoscopic group
versus 63.0 min (30.0-151.0) in the open group, (P < 0.05). Length of stay was
similar, 5 days in the laparoscopic and in the open group, (P = 0.945). The
incidence of shunt failure during the entire follow-up period was not
statistically different between the two groups, occurring in 14.1% in the
laparoscopic group and 16.9% in the open group, (P = 0.601). Kaplan-Meier
analysis demonstrated no difference in shunt survival between the two groups (P =
0.868), with functionality in 85% at 6-months and 78.5% at 1-year. CONCLUSION:
According to our study, LVPS-placement results compare similarly to OVPS
placement in most aspects. Since laparoscopic placement is not routinely
indicated, we suggest a prospective study to assess its value as an alternate
technique especially suitable in obese patients and patients with previous
abdominal operations.
PMID- 25126124
TI - Bed wise cost analysis of in-patient treatment of brachial plexus injury at a
Level I trauma Center in India.
AB - AIM: The aim was to calculate, in monetary terms, total cost incurred by a Level
I trauma center in providing in-patient care to brachial plexus injury patients
during their preoperative and the postoperative stay. SUBJECTS AND METHODS: All
patients of brachial plexus injury admitted and discharged between January and
December 2010 were included in the study. Total cost per bed was calculated under
several cost heads in pre- and post-operative ward care. Intra-operative costs
were excluded. RESULTS: A total of 69 patients were admitted in the year 2010. Of
these 60 were operated and the rest were planned conservative management. The
total cost incurred by the trauma center in providing in-patient care to patients
admitted in the ward, excluding high dependency unit, came out to be Rs.
3,650.00/patient/bed/day. Of this Rs. 2,234.645, the maximum amount was incurred
in providing manpower alone. The average preoperative wait was 12 days (maximum
41 days and minimum 1-day). The average postoperative stay was 2 days. Total cost
incurred in the preoperative period was Rs. 2,975,125 (US$ 59392) or Rs.
43,117/patient (US$ 861). It was Rs. 386,948 (US$ 7724) in the postoperative
period (Rs. 6,449 or US$ 129/patient). Nine patients were not operated and had
waited from 2 to 12 days before finally being planned for observant treatment.
This itself cost the hospital Rs. 226,328 (US$ 4518). CONCLUSION: By just
reducing the preoperative length of stay to 1-day the cost can be brought down by
93% for brachial plexus injury patients alone and the beds can be used to admit
more critical patients.
PMID- 25126123
TI - EC-IC bypass for cavernous carotid aneurysms: An initial experience with twelve
patients.
AB - AIMS: Need for performing a bypass procedure prior to parent artery occlusion in
patients with good cerebral vascular reserve is controversial. We analyze our
experience of 12 giant internal carotid artery aneurysms treated with
extracranial-intracranial (EC-IC) bypass and proximal artery occlusion. MATERIALS
AND METHODS: Retrospective analysis of the case records of all complex carotid
aneurysms operated in our institute since January 2009. RESULTS: The study
included eleven cavernous carotid aneurysms and one large fusiform cervical
carotid aneurysm reaching the skull base. Preoperative assessment of cerebral
vascular reserve was limited to Balloon test occlusion with hypotensive
challenge. Eleven patients who successfully completed a Balloon test occlusion
(BTO) underwent low flow superficial temporal artery to middle cerebral artery
(STA-MCA) bypass, while one patient with a failed BTO underwent a high flow
bypass using a saphenous vein graft. Parent artery ligation was performed in all
patients following the bypass procedure. Check angiogram revealed thrombosis of
the aneurysm in all patients with a graft patency rate of 81.8%. We had one
operative mortality, probably related to a leak from the anastomotic site. The
only patient who had a high flow bypass developed contralateral hemispheric
infarcts and remained vegetative. All the other patients had a good recovery and
with a Glasgow outcome score of 5 at last follow-up. CONCLUSION: We feel that
combining EC-IC bypass prior to parent vessel occlusion helps in reducing the
risk of post operative ischemic complications especially in situations where a
complete mandated cerebral blood flow studies are not feasible.
PMID- 25126125
TI - Multicystic oligodendroglioma with calvarial destruction.
AB - CONTEXT: Calvarial erosion is known to occur with some superficially located
tumors. Very few case reports of calvarial erosion associated with
oligodendroglioma are reported in the literature, but calvarial destruction with
oligodendroglioma is very rare. AIM: To report an unusual case of multicystic
frontoparietal oligodendroglioma with destruction of the calvaria and scalp
involvement in the absence of prior surgery or radiation. MATERIALS AND METHODS:
A 30-year-old male presented with the history of left focal seizure with
secondary generalization for last three to four years along with left sided
weakness for the past one month. There was history of slowly progressive
decreased vision in both eyes leading to complete blindness in both eyes for the
past one month. On neurological examination, patient had left hemiparesis of
grade-2/5 with perception of light absent in both eyes. Fundus examination
revealed bilateral optic atrophy. Magnetic resonance imaging (MRI) of the brain
showed a large supratentorial heterogenous multicystic ring enhancing mass lesion
involving right frontal lobe, right frontotemporal opercular region, and
posteriorly abutting the central sulcus and anteriorly destroying the calvaria.
Patient underwent right frontoparietal craniotomy and near total excision of
tumor. Histopathological examination revealed oligodendroglioma WHO grade-2.
Patient received postoperative chemoradiotherapy. RESULTS: At nine month follow
up patient neurological status was same and his seizure was controlled on single
AED. There was no recurrence of seizure at nine month of follow-up. CONCLUSIONS:
Calvarial destruction in association with extra and intra axial neoplasm should
include oligodendroglioma especially in patients with long history of symptoms,
although calvarial destruction is very rare. However, the final diagnosis is
established by means of histopathological examination.
PMID- 25126126
TI - Intradural spinal granular cell tumor.
AB - Granular cell tumor is a rare, usually benign tumor with classical
histomorphology. Location of tumor varies widely within body, but spine is
distinctly a rare location for this tumor. We report a rare case of granular cell
tumor involving intradural extramedullary portion of lumbar region of spinal
cord. Knowledge of which is important as subsequent prognosis differs from other
tumor at same location.
PMID- 25126127
TI - Primary Ewing's sarcoma of cervical vertebra: An uncommon presentation.
AB - Ewing's sarcoma is a malignant primary bone tumor primarily seen in the long
bones. Primary Ewing's sarcoma of the cranium is quite uncommon occurring in 1%
of the cases. We report the occurrence of this rare lesion in a 24-year-old male
presenting with progressively increasing swelling in left mastoid region
mimicking a mastoid abscess which was later diagnosed on Fine needle aspiration
cytology (FNAC) as a small round cell tumor as Ewing's sarcoma. Contrast enhanced
computed tomography (CECT) revealed a typical moth eaten appearance in the first
and second cervical vertebra.
PMID- 25126128
TI - Thoracic cord compression by extramedullary hematopoiesis in thalassemia.
AB - Extramedullary hematopoiesis (EMH) refers to hematopoiesis occurring outside the
medulla of bone. It may be physiologic or due to pathological conditions like
hematopoietic disorders. EMH can involve liver, spleen, thorax, and lymph nodes.
It can involve paraspinal tissues with extension and involvement of spinal canal.
In our case, the diagnosis was confirmed by the history of the patient stating
underlying hematological condition and by magnetic resonance imaging (MRI)
findings showing large soft tissue masses in paraspinal areas with involvement of
spinal canal and leading to cord compression.
PMID- 25126129
TI - Aneurysmal bone cyst: An unusual presentation of back pain.
AB - Aneurysmal bone cyst (ABC) is a rare benign tumor comprising 1.4% of all primary
bone tumors. It commonly involves humerus, femur, tibia, and pelvic bones. Spinal
involvement is rare. The pathological appearance of the lesion is one of the
blown out distension with fluid filled cavities from which it gains the name
aneurysmal bone cyst. The World Health Organization has defined it as an
expanding lesion with blood filled cavities separated by septa of trabecular bone
or fibrous tissue containing osteoclast giant cells. We describe the case of a 20
year-old Asian male who presented with backache and pain in right leg. Radiology
was suggestive of an ABC involving the posterior elements of the lumbar vertebra.
Excision was performed. We discuss this unusual case, reviewing the current
literature on biological behavior and management of aneurysmal bone cyst.
PMID- 25126130
TI - Spheno-orbital encephalocele: A rare entity - A case report and review of
literature.
AB - OBJECTIVE: To report a rare case of basal encephalocele (spheno-orbital
encephalocele), managed successfully in our institute. This is one of the rarest
type of encephaloceles with very little literature available. In this case,
sphenoid dysplasia was not associated with type 1 Neurofibromatosis. SETTINGS:
Grant Medical College and Sir J.J Group of Hospitals, Byculla, Mumbai,
Maharashtra, India. METHODS: A 22 year old male presented with a history of
protrusion of right eye since the age of 7 years followed by progressive
diminution of vision in the same eye for 5 months. MRI scan was suggestive of
sphenoid dysplasia with herniation of right fronto-temporal lobe. The patient was
operated upon with right frontal craniotomy with excision of encephalocele and
repair of skull base. Subsequently, the patient underwent plastic surgery for
facial skin remodeling. RESULTS: Patient's encephalocele reduced completely after
excision and repair with good cosmetic results and no neurological deficits.
There is no evidence of recurrence till recent follow-up. CONCLUSION: Basal
encephaloceles are very rare. Complete excision of encephalocele with repair of
the defect should be the aim to achieve cure.
PMID- 25126131
TI - Epidural hematoma secondary to solitary skull metastasis from an ovarian
carcinoma.
AB - We report a rare case of an acute epidural hematoma (EDH) due to solitary skull
metastasis in a 60-year-old patient treated earlier for ovarian carcinoma. The
patient presented with head injury followed by unconsciousness and computerized
tomography showed a large EDH in the right parietal region along with a contusion
of left temporal-parietal lobe and subarachnoid hemorrhage in left sylvian
fissure. Emergency craniotomy and evacuation of the EDH was performed and the
hemorrhage was determined to be secondary to skull metastasis of ovarian
carcinoma; the patient recovered and received whole brain radiation therapy.
PMID- 25126132
TI - Designing and Developing Open Education Resources in Higher Education: A
Molecular Biology Project.
AB - Recent advances in internet technology have transformed how we gather and share
information in today's world and have provided us with a platform to access
educational resources and related information on the Internet. Every day, new
technologies are developed that are changing the when and where we access that
information. The capabilities of new technologies have allowed society to access
information and learn virtually anywhere. As technical ingenuity continues to
generate new technologies and paths of communication, we must look for
opportunities to collaborate, share and extend our educational resources in
higher education. Distributing Open Educational Resources (OER) in the form of
freely licensed materials is necessary in order to laterally influence current
advances in learning technologies. Online resources are being used in a variety
of contexts to supplement instruction and training at higher education
institutions. The aim of this Open Educational Resource project was to design and
develop a blended learning instructional program to assist online users in
developing familiarity with laboratory techniques prior to conducting molecular
biology research in an authentic laboratory setting. This paper will look at the
background of OER, describe the online materials that the Center for
Cardiovascular Research (CCR) developed for open use, and discuss the outcomes
and implications for use.
PMID- 25126133
TI - Mindful Parenting Assessed Further: Psychometric Properties of the Dutch Version
of the Interpersonal Mindfulness in Parenting Scale (IM-P).
AB - Psychometric properties of the Dutch version of the Interpersonal Mindfulness in
Parenting Scale (IM-P) were studied in a general population sample of mothers of
adolescents (n=866) (study 1). A six-factor structure (29 items) emerged using
exploratory factor analysis. A main difference from the original IM-P was that
aspects of compassion and emotional awareness were separated into different
factors for the self and the child, instead of combined into one factor. In a
second general population sample of mothers of adolescents (n=.99), the six
factor structure was confirmed using confirmatory factor analysis (study 2). The
proposed 29-item version of the IM-P and its subscales were shown to have good
internal consistencies, apart from the sixth factor. As expected, a high
correlation was found with general mindfulness questionnaires (FFMQ and FMI).
Furthermore, the IM-P correlated positively as expected with quality of life and
optimism and negatively with depression and dysfunctional parenting styles. These
expected indications of construct validity were found in study 2, as well as in
mothers (n=112) of adolescents with type 1 diabetes mellitus (study 3) which was
added to examine whether the Dutch version of the IM-P was also valid in a
pediatric population. Overall, these three studies present good psychometric
properties of the Dutch translation of the first measure of mindful parenting.
PMID- 25126135
TI - Impact of an educational intervention on steroid prescribing and dosing effect on
patient outcomes in COPD exacerbations.
AB - The increasing number of patients affected by chronic obstructive pulmonary
disease (COPD) and associated exacerbations has led to both rising hospital
admissions and significant economic impact. Evidence-based guidelines have been
formulated for COPD management recommending the use of low dose, oral
corticosteroid therapy in the treatment of exacerbations. However, fewer than 50%
of physicians' prescribing practices appropriately reflect the published clinical
guidelines on the use of systemic corticosteroids in these patients. OBJECTIVE:
The purpose of this study was to evaluate the impact of a pharmacist-led
educational intervention on prescribing practices and patient outcomes when using
systemic corticosteroids in patients with COPD exacerbations. METHODS: This
retrospective case-control study included patients admitted to an inpatient
family medicine service with a COPD exacerbation who received systemic
corticosteroids. Two pharmacist-led educational interventions were delivered to
prescribers to review current guidelines for managing COPD exacerbations with
systemic corticosteroids. Patients were retrospectively identified over a three
month span prior to and following the educational intervention. Data was
collected via chart review to evaluate prescribing practices prior to and
following the educational sessions. In addition, data was collected to evaluate
the effects of an educational intervention on length of stay, adverse events, and
cost of treatment. RESULTS: A total of 23 pre-intervention patients and 18 post
intervention patients met inclusion criteria. After pharmacist-led interventions,
guidelines were not more likely to be adhered to by prescribers when compared to
guideline adherence in the pre-intervention patients. Because no statistically
significant change in guideline adherence was observed, there was no impact on
secondary outcomes. CONCLUSION: Pharmacist-led didactic educational interventions
and guideline dissemination do not improve guideline adherence and prescribing
practices with respect to systemic corticosteroids in COPD exacerbations.
PMID- 25126134
TI - Medication adherence: a review of pharmacy education, research, practice and
policy in Finland.
AB - AIMS: To describe pharmacy education, research, practice and policy related to
medication adherence in Finland since the year 2000. METHODS: The three
universities that provide pharmacy education (Abo Akademi, University of Eastern
Finland, and University of Helsinki) completed a structured pro-forma
questionnaire regarding education related to medication adherence. A MEDLINE and
EMBASE literature search was performed to identify English language peer-reviewed
research that reported medication compliance, adherence or persistence. The
Ministry of Social Affairs and Health was invited to nominate policies and
documents related to medication adherence. A narrative review of medication
counselling practices and professional service delivery through Finnish community
pharmacies was undertaken. RESULTS: Medication adherence was a theme integrated
into obligatory and elective courses for bachelors and masters degree students.
The literature search identified 33 English language peer-reviewed research
articles reporting medication compliance, adherence or persistence published
since the year 2000. Policy documents of the Ministry of Social Affairs and
Health recognise that poor medication adherence may lead to suboptimal treatment
outcomes, and encourage patient participation in treatment decision making.
Adherence practice in Finnish pharmacies has been strongly linked to the
development of medication counselling services. CONCLUSIONS: Adherence research
and education has focused on understanding and addressing the contextual factors
that contribute to medication nonadherence. Adherence practice in community
pharmacies has tended to focus on medication counselling and programs specific to
particular disease states. Medication adherence is a topic that is integrated
into courses for bachelor's and master's level pharmacy students in Finland.
PMID- 25126136
TI - Physicians' generic drug prescribing behavior in district hospitals: a case of
Phitsanulok, Thailand.
AB - Generic prescribing is a sound approach to contain health care costs. However,
little is known about physicians' prescribing patterns in the Thai context.
OBJECTIVE: To explore physicians' generic prescription patterns in district
hospitals. METHODS: Data was collected from three of the eight district hospitals
between January and December 2008 (final response rate 37.5%). All participating
hospitals were between 30 and 60-bed capacity. The researchers reviewed 10% of
total outpatient prescriptions in each hospital. RESULTS: A total of 14,500
prescriptions were evaluated. The majority of patients were under universal
health coverage (4,367; 30.1%), followed by senior citizens' health insurance
(2,734; 18.9%), and civil servant medical benefit schemes (2,419; 16.7%). Ten
thousand six hundred and seventy-one prescriptions (73.6% of total prescriptions)
had at least one medication. Among these, each prescription contained 2.85
(SD=1.69) items. The majority of prescriptions (7,886; 73.9%) were prescribed by
generic name only. Drugs prescribed by brand names varied in their
pharmacological actions. They represented both innovator and branded-generic
items. Interestingly, a large number of them were fixed-dose combination drugs.
All brand name prescriptions were off patented. In addition, none of the brand
name drugs prescribed were categorized as narrow therapeutic range or any other
drug that had been reported to have had problems with generic substitution.
CONCLUSION: The majority of prescriptions in this sample were written by generic
names. There is room for improvement in brand name prescribing patterns.
PMID- 25126137
TI - Impact of emergency contraception status on unintended pregnancy: observational
data from a women's health practice.
AB - OBJECTIVE: This study aimed to determine if nonprescription emergency
contraception (EC) availability impacted self-reported unintended pregnancy rates
and to assess women's knowledge and awareness of EC prior to and after
nonprescription availability. METHODS: A survey regarding contraception use and
knowledge was verbally administered to a cross-sectional, convenience sample of
272 pregnant women receiving prenatal care at a large urban community women's
clinic between August 2003 and October 2008. Statistical analyses determined the
differences between two groups (before [BA] and after, [AA] non-prescription EC
availability in the U.S. drug market) in terms of self-reported unintended
pregnancy rates, knowledge and awareness of EC. RESULTS: The AA group reported
higher incidence of unintended pregnancy when compared to the BA group (90.7% vs.
72.7%, P = 0.0172). The majority of both groups reported that they were not using
any contraception at the time of conception (BA-84.4%; AA-83.3%). There was no
significant difference in the participants' awareness of EC between the two
groups (BA-46.8% vs. AA-43.0%) nor was there a significant difference between the
two groups in the self-reported willingness to use EC in the future (BA-53.1% vs.
AA-63.4%). However, among participants who were unaware of EC, 61% reported they
would consider using it in the future after receiving brief EC counseling from a
pharmacist or student pharmacist. Neither age nor pregnancy intention was
associated with self-reported EC awareness but there was an association with
income (P = 0.0410) and education (P = 0.0021). CONCLUSION: The change from
prescription-only to non-prescription status of EC in the U.S. drug market did
not impact the unintended pregnancy rate in this patient population. Lack of
knowledge and awareness is still a major barrier to widespread EC use.
PMID- 25126138
TI - Pattern and quality of scientific communications on drug safety produced by a
regional pharmacovigilance center in Nepal.
AB - Analyzing the pattern and quality of scientific communications on
pharmacovigilance can help the regional centers in Nepal and other developing
countries to develop approaches for communicating effectively medicine safety
issues. This kind of research is lacking in developing countries. OBJECTIVES: To
analyze the pattern and quality of scientific communications on drug safety
produced by the regional pharmacovigilance center at western Nepal. METHODOLOGY:
Various conference abstracts and journal publications produced by the center
during its initial four years of establishment (14th September 2004 till 13th
September 2008) were identified. These communications were categorized in to case
reports, review articles, conference presentations, short communications,
newsletter and bulletin articles, original research and case series. In addition,
the quality of the case reports were evaluated as per International Society of
Pharmacovigilance/International Society of Pharmacoepidemiology (ISoP/ISPE)
guidelines on the requirements for submitting case reports on adverse event
reports in biomedical journals. RESULTS: During the study period, 53 scientific
communications were produced by the staff of the regional pharmacovigilance
center in relation with drug safety. Among these, 18 (34%) were related to case
reports and letters. The median (interquartile range) age of the patients
described in the case reports was 46.5 (21.7-51.2) years. Among the total 18
ADRs, four were fixed drug eruptions, followed by contact dermatitis (n=2).
Majority of the published case reports were related to skin (n=13; 72.2%).
Antimicrobials were responsible for 27.8% (n=5) of the case reports. Among the 18
case reports published by the pharmacovigilance center, a majority followed the
ISoP/ISPE guidelines. Few parameters like physical examination of the patient
experiencing ADR, patient disposition, dosage and administration of the suspected
drugs, and drug-reaction interface were missing in few of the cases. CONCLUSION:
A high percentage of the scientific communications were 'case reports'. A high
proportion of the case reports produced by the center were of international
standards. There were lacunae in 'patient disposition' in few of the reports.
PMID- 25126139
TI - Patients' blood pressure knowledge, perceptions and monitoring practices in
community pharmacies.
AB - Hypertension is a modifiable risk factor for cardiovascular disease. Despite
this, patients often cannot or inaccurately estimate their risk factors.
OBJECTIVES: IN ORDER TO IMPROVE PHARMACIST INTERVENTIONS, WE SOUGHT TO: 1) find
out patients' knowledge about blood pressure (BP) and their self-monitoring
behaviors and 2) identify the relationships between these two elements.
Specifically, if evaluation of BP control were related to knowledge of one's BP
level and self-monitoring habits, and if knowledge of one's target and BP level
varied with monitoring habits. METHODS: Final year pharmacy students were trained
and interviewed patients in community pharmacies as a required exercise in their
pharmacy clerkship. Each student recruited a convenience sample of 5-10 patients
who were on hypertension medication, and surveyed them regarding their BP
targets, recent BP levels as well as monthly and home BP monitoring practices.
RESULTS: One third of the 449 patients interviewed were able to report a blood
pressure target with 26% reporting a JNC 7 recognized target. Three quarters of
patients who reported a blood pressure target were able to report a blood
pressure level, with 12% being at their self-reported target. Roughly two thirds
of patients perceived their BP to be "about right", and slightly less than a
third thought it to be "high". Sixty percent of patients monitor their BP
monthly, but less than 50% of patients practice home BP monitoring. CONCLUSIONS:
This study along with others before it point to the knowledge and self-management
gaps in patients with chronic conditions. Furthermore, pharmacy students were
able to use a brief intervention to screen patients during routine care.
Pharmacists can help improve patient understanding and promote increased self
management through regular BP monitoring.
PMID- 25126140
TI - Influence of population and general practice characteristics on prescribing of
minor tranquilisers in primary care.
AB - Prevalence of generalised anxiety disorders is widespread in Great Britain.
Previous small-scale research has shown variations in minor tranquiliser
prescribing, identifying several potential predictors of prescribing volume.
OBJECTIVE: This study aimed to investigate the relationship between general
practice minor tranquiliser prescribing rates and practice population and general
practice characteristics for all general practices in England. METHODS: Multiple
regression analysis of minor tranquiliser prescribing volumes during 2004/2005
for 8,291 English general practices with general practice and population
variables obtained from the General Medical Services (GMS) statistics, Quality
and Outcomes Framework (QOF), 2001 Census and 2004 Index of Multiple Deprivation
(IMD). RESULTS: The highest rates of minor tranquiliser prescribing were in areas
with the greatest local deprivation while general practices situated in areas
with larger proportions of residents of black ethnic origin had lower rates of
prescribing. Other predictors of increased prescribing were general practices
with older general practitioners and general practices with older registered
practice populations. CONCLUSION: Our findings show that there is wide variation
of minor tranquilisers prescribing across England which has implications
regarding access to treatment and inequity of service provision. Future research
should determine the barriers to equitable prescribing amongst general practices
serving larger populations of black ethnic origin.
PMID- 25126141
TI - Pattern of adverse drug reactions reported by the community pharmacists in Nepal.
AB - The pharmacovigilance program in Nepal is less than a decade old, and is hospital
centered. This study highlights the findings of a community based
pharmacovigilance program involving the community pharmacists. OBJECTIVES: To
collect the demographic details of the patients experiencing adverse drug
reactions (ADR) reported by the community pharmacists; to identify the common
drugs causing the ADRs, the common types of ADRs; and to carry out the causality,
severity and preventability assessments of the reported ADRs. METHODS: The
baseline Knowledge-Attitude-Practices (KAP) of 116 community pharmacists from
Pokhara valley towards drug safety was evaluated using a validated (Cronbach
alpha=0.61) KAP questionnaire having 20 questions [(knowledge 11, attitude 5 and
practice 4) maximum possible score 40]. Thirty community pharmacists with high
scores were selected for three training sessions, each session lasting for one to
two hours, covering the basic knowledge required for the community pharmacists
for ADR reporting. Pharmacist from the regional pharmacovigilance center visited
the trained community pharmacists every alternate day and collected the filled
ADR reporting forms. RESULTS: Altogether 71 ADRs, from 71 patients (37 males)
were reported. Antibiotics/ antibacterials caused 42% (n=37) of the total ADRs
followed by non steroidal anti-inflammatory drugs [25% (n=22)].
Ibuprofen/paracetamol combination accounted for ten ADRs. The most common type of
ADR was itching [17.2 % (n=20), followed by generalized edema [8.6 % (n=10)]. In
order to manage the ADRs, the patients needed medical treatment in 69% (n=49) of
the cases. Over two third (69%) of the ADRs had a 'possible' association with the
suspected drugs and a high percentage (70.4%) were of 'mild (level 2)' type.
Nearly two third [64.7 % (n=46)] of the ADRs were 'definitely preventable'.
CONCLUSION: The common class of drugs known to cause ADRs was antibacterial/
antibiotics. Ibuprofen/ Paracetamol combination use of the drug was responsible
for more number of ADRs and the most common ADRs were related to dermatological
system. Strengthening this program might improve safe use of medicines in the
community.
PMID- 25126142
TI - Adherence policy, education and practice - an international perspective.
AB - Nonadherence to chronic therapy has become a large burden on the healthcare
system of many countries. Community pharmacists are well positioned to address
nonadherence as part of their overall patient care activities, and contribute to
patients' quality use of medicines. Between 2008 and 2010, a series of narrative,
peer-reviewed articles were published in Pharmacy Practice which focused on
community pharmacists' activities in medication adherence, specifically in the
areas of the education they receive, their practice, the research conducted and
national or local policies. This editorial aims to summarise the key findings
presented in the series, and highlight the pertinent issues and gaps in the
literature. There is a need to implement global and long-term objectives
focussing on enhancing the quality of education and competencies of community
pharmacists and the research conducted in medication adherence, to develop
guidelines for pharmacists and enhance the uptake of adherence promoting services
in routine care.
PMID- 25126143
TI - Granulocyte colony-stimulating factor use in a large British hospital: comparison
with published experience.
AB - Granulocyte colony-stimulating factors (G-CSF) are high-cost agents recommended
as prophylaxis of febrile neutropenia or as adjunctive treatment of severe
neutropenic sepsis. Their use in high-risk situations such as acute myeloid
leukaemia, acute lymphocytic leukaemia, myelodysplastic syndrome and stem cell
transplantation is also indicated. OBJECTIVE: This audit assessed the use of G
CSF within the Oncology and Haematology Service Delivery Unit at Guy's and St.
Thomas' hospital (London, United Kingdom). METHODS: Patients who received G-CSF
in April-May 2008 were identified retrospectively from the pharmacy labelling
system, and chemotherapy front sheets, clinic letters and transplantation
protocols were reviewed. Patients on lenograstim, in clinical trials or under non
approved chemotherapy protocols were excluded. RESULTS: A total of 104 G-CSF
treatments were assessed. The most commonly treated malignancy was breast cancer
(41.3%), with docetaxel 100 mg/m (2) (34.6%) being the most frequent chemotherapy
regimen. The chemotherapy intent was curative in 66.3 % of cases. Pegfilgrastim
was used in 73.1 % of cases and primary prophylaxis was the most common
indication (54.8%). Stem cell transplantation was the first indication to meet
the audit criterion (93.3%), followed by primary prophylaxis (89.5%). There was a
considerable nonadherence for secondary prophylaxis (6.7%). CONCLUSION: The
overall level of compliance with the audit criteria was 72.1%. The results for
primary and secondary prophylaxis would have been different if FEC100
(fluorouracil, epirubicin, cyclophosphamide) and docetaxel 100 mg/m (2) had been
considered a single chemotherapy regimen. Also, the lack of access to medical
notes may have affected the reliability of the results for 'therapeutic' use.
PMID- 25126144
TI - Knowledge and use of folic acid among college women: a pilot health promotion
program led by pharmacy students and faculty.
AB - As pharmacists and pharmacy students are increasingly called upon to assume roles
in public health activities, it is important to recognize unique opportunities to
educate community members on health, wellness, and disease prevention. OBJECTIVE:
To evaluate the impact of a pilot health promotion program on college women's
knowledge regarding folic acid and prevention of neural tube defects (NTD) and
frequency of multivitamin use. METHODS: A health promotion program was developed
by a pharmacy student and two pharmacy faculty members that included an oral
presentation and reminder messages. A multiple-choice test assessing knowledge of
folic acid and NTD and frequency of multivitamin use was given to participants
before and immediately after the presentation. Participants then received a
reminder message regarding folic acid once a week for three weeks. Knowledge and
multivitamin use were reassessed four weeks post-intervention. RESULTS: Thirty
two college women voluntarily attended the oral presentation. Twenty-five women
(78.2%) completed the four-week post-test. Compared to the pre-test, there were
statistically significant increases in average test score (p<0.0001) and correct
responses to questions regarding folic acid and NTD (p<0.05 for each question).
Participants reported a statistically significant increase in regular (>=4
times/week) multivitamin use (p=0.023). CONCLUSION: Participants in the pilot
health promotion program demonstrated a statistically significant increase in
knowledge about folic acid and frequency of multivitamin use. A similarly-modeled
health promotion program may be an effective way of increasing folic acid and NTD
knowledge and changing behaviors of multivitamin use in college women.
PMID- 25126145
TI - Medication storage and self-medication behaviour amongst female students in
Malaysia.
AB - OBJECTIVES: The aims of this study are to determine the prevalence, attitudes and
behaviours of medication storage and self-medication amongst female students at
Universiti Sains Malaysia (USM). METHODS: A cross-sectional survey was conducted
and cluster random sampling technique was used for respondent selection. A pre
piloted questionnaire was administered to female respondents so as to collect the
data. Data was analyzed using SPSS version 12 and analysis was conducted using
descriptive analysis procedures. RESULTS: Of the 481 participants (mean age; SD
was 22.1; 3.3), 93.1% (n=448) students stated that they stored medicine in their
rooms, while 70.7% (n=340) stated that they stopped taking a prescribed medicine
without consulting a doctor. The prevalence of self-medication was 80.9% (n=389).
The most common reasons for self-medication were related to their knowledge of
their ailment and its treatment (58.0%), 14.4% thought it saved time and 8.5%
mentioned that medication given by provider was not effective. The most common
symptoms were otorhinolaryngology problems (22.5%), followed by respiratory
disease (19.6%), Gastro Intestinal Tract (GIT) disease (18.1%) and headache/fever
(16.8%). Commonly used medicines were analgesics & antipyretics (30.2%), ear,
nose & throat drugs (10.8%), vitamins & minerals (10.8%), GIT drugs (8.5%), anti
infections (7.3%) and herbal medicines (3.5%). Prevalence of medicine storage and
self-medication practice is high among educated female students in USM.
CONCLUSIONS: There is a need to educate the students to ensure safe practice by
increasing their awareness. Strict policies need to be implemented on the
unrestricted availability of medicines so as to prevent the wastage of medicines.
PMID- 25126146
TI - Self medication among hospitalized patients in selected secondary health
facilities in South Western Nigeria.
AB - Practice of self-medication has not been evaluated in hospitalized patients
especially in Nigerian hospitals. OBJECTIVES: To evaluate the practice of self
medication among hospitalized patients with an aim to unearth some of the reasons
for, and perceptions of benefits of this type of behaviour in secondary health
care facilities. METHODS: This study was carried out among 197 in-patients
admitted in three secondary health facilities in southwestern Nigeria using
structured questionnaire. Effects of variables such as age, gender and marital
status on the practice of self medication were also evaluated using the Fisher's
Exact test at p<0.05 as level of significance. RESULTS: Response rate of the
study was 93.8% with 174 respondents (88.3%) perceived that the medications
prescribed for them were efficacious. Almost 38% of the respondents were self
medicating, with herbal medicines (29.2%) and western medicines (37%) partly due
to side effects of the prescribed medicines. Thirty one (15.7%) respondents
obtained medicines for self medication through relatives and friends.
Prescription medicines used for self medication constituted 7.5%. Major reasons
given for self medication included habit, availability and necessity. Ninety
respondents (35.7%) had been informed by health care personnel about possible
side effects of the medications. Ninety six respondents (48.7%) experienced side
effects with the prescribed medications and was a major reason for self
medication. Seventy six respondents (79.2%) who had side effects or other
secondary symptoms informed healthcare personnel in the hospital while 16 (16.7%)
informed relatives and friends. There was statistically significant association
between age and the action taken on whom was informed (p=0.001). CONCLUSIONS:
There is need for extra vigilance from health personnel directly responsible for
care of hospitalized patients to look for incidences of self-medication and
patient education on the negative aspects of administering undisclosed medicines
to their health care givers especially while they are hospitalized.
PMID- 25126147
TI - New Zealand parent's perceptions of the use and safety of over the counter liquid
analgesics.
AB - OBJECTIVE: The objective of this study was to investigate the knowledge of
parents and caregivers with respect to the purchase, use and storage of liquid
analgesics purchased over the counter (OTC) from pharmacies. This would enable
specific strategies to be identified to increase awareness of the potential risks
of these products. METHODS: Questionnaires were developed and used a combination
of Likert Scales, open ended questions and yes/no answers. Randomly chosen New
Zealand pharmacies (463) were asked to approach a person purchasing liquid
analgesics and ask them to complete the questionnaire. Of the 105 pharmacies that
participated, 96 completed parent/caregiver questionnaires were returned.
RESULTS: When choosing a product there was a statistically significant difference
between the most important factors 'safety' and 'active ingredient' and the least
important factors 'cost' and if the parent/caregiver 'used it before'. All
parents/caregivers claim to have received verbal information from pharmacy staff,
with 40% stating that they 'always' receive information. The majority of
parents/caregivers store medicines in a high place (n=61), in a cupboard (n=56)
or a combination of these. Over half (52%) of the parents/caregivers thought that
children could 'never' open child resistant closures. CONCLUSION: Whilst parents
and caregivers choose products based on perceived safety, there is an over
estimation in the perception of the protection that a child resistant closure
actually offers. The general public needs to continually be vigilant in the use,
storage and administration when using medication in the vicinity of children.
PMID- 25126148
TI - Increasing use of artemisinin-based combination therapy for treatment of malaria
infection in Nigerian hospitals.
AB - OBJECTIVES: This study aimed at describing the pattern of outpatient antimalarial
drug prescribing in a secondary and a tertiary hospital, and to assess adherence
to the National Antimalarial Treatment Guideline (ATG). METHODS: An audit of
antimalarial prescription files from the two health facilities for a period of
six months in 2008 was conducted. Semi structured questionnaires were used to
collect information from the doctors and pharmacists on their awareness and
knowledge of the National Antimalarial Treatment Guideline. RESULTS: Artemisinin
based combination therapies (ACTs) were the most prescribed antimalarials.
Overall, 81.4% of the total prescriptions contained ACTs, out of which 56.8% were
artemetherlumefantrine. However, adherence to the drugs indicated by national
guideline within the DU90% was 38.5% for the tertiary and 66.7 % for the
secondary hospital. The standard practice of prescribing with generic name was
still not adhered to as evidenced in the understudied hospitals. The percentage
of health care providers that were aware of the ATG was 88.2% for doctors and
85.1% for pharmacists. However, 13.3% and 52.2% of doctors and pharmacists
respectively could not properly list the drugs specified in the guideline.
Amodiaquine was the most commonly preferred option for managing children aged 0 -
3 months with malaria infection against the indicated oral quinine. CONCLUSION:
This study showed an increased use of artemisinin-based combination therapy for
the treatment of uncomplicated malaria compared previous reports in Nigeria. This
study also highlights the need for periodic in-service quality assurance among
health professionals with monitoring of adherence to and assessment of knowledge
of clinical guidelines to ensure the practice of evidence based medicine.
PMID- 25126149
TI - Evaluation of a pharmacist-managed diabetes medication therapy adherence clinic.
AB - Patient adherence to prescribed medication regimens is important in diabetes care
to prevent or delay microvascular and macrovascular complications such as
retinopathy, nephropathy and myocardial infarction. In Penang Hospital, Malaysia,
pharmacists collaborate with physicians in diabetes care through a pharmacist
managed Diabetes Medication Therapy Adherence Clinic (DMTAC) in the Endocrine
Clinic, in operation since 2006. OBJECTIVE: To evaluate the effectiveness of the
pharmacist-managed DMTAC program in improving glycaemic control, lipid parameters
and patients' medication adherence. METHOD: A retrospective study among patients
enrolled in the DMTAC program was conducted between September 2007 and December
2008. Data was included from patients with a glycosylated haemoglobin (HbA1c) >8%
and who had completed eight visits with the pharmacists. Medical records and
DMTAC forms that provided patients' demographics, medication regimens, adherence
and laboratory parameters as well as pharmacists' interventions were reviewed.
HbA1c, fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL),
triglycerides (TG) and high-density lipoprotein cholesterol (HDL) were evaluated.
Documented data of patients' adherence to medication regimen [Modified Morisky
Medication Adherence Score (MMMAS); high adherence if score >8, medium adherence
if score 6 to <8 and low adherence if score <6] was also evaluated. RESULTS: A
total of 43 patients (53.5% females; 46.5% Malays, 44.2% Chinese and 9.3%
Indians) were included in the analysis. A mean reduction in HbA1c of 1.73%
(p<0.001), mean reduction in FBG of 2.65mmol/l (p=0.01) and mean reduction in LDL
cholesterol of 0.38mmol/l (p=0.007) were achieved. The difference in TG and HDL
cholesterol were not significant. Patients' adherence to medication regimens
improved significantly with an increase in the mean MMMAS score from 7.00 to
10.84 (p<0.001) after completion of the DMTAC program. CONCLUSION: The pharmacist
managed DMTAC program resulted in significant improvements in HbA1c, glucose and
LDL cholesterol levels as well as medication adherence in patients with diabetes.
PMID- 25126150
TI - Educational innovations: Categories of bulletin board postings designed to
increase awareness of contemporary pharmaceutical policy issues.
AB - OBJECTIVE: The goal of this project was to categorize and classify bulletin board
postings pertaining to pharmaceutical policy from both the professional and lay
press. METHODS: Bulletin board postings were used to supplement in-class
discussion to keep students, faculty and staff up-to-date on emerging trends. A
bulletin board located in the main classroom area of the College of Pharmacy
Building where students would pass by on the way to class and congregate during
break periods was used to display articles from various sources concerning topics
related to pharmaceutical policy. Information is presented about the primary
subject matters addressed in the articles, the types of publications from which
they were drawn, and the top ten sources of articles displayed. RESULTS: This
project showed that coverage of issues related to pharmacists is predominantly
seen in newspapers and most pertinent issues are business related. CONCLUSIONS:
It can be seen from this analysis that the issues facing pharmacists are varied.
The pharmaceutical policy field is transforming and many of these changes are
very relevant to the general population. This is seen from the coverage of all of
these issues in the lay press.
PMID- 25126151
TI - Pancreatic Lipomas - Prevalence in Patients Undergoing Abdominal CT.
AB - BACKGROUND: Pancreatic lipomas are reported to be rare but their prevalence is
unknown. This study examined the prevalence of pancreatic lipomas in a sample of
patients undergoing abdominal computed tomography. MATERIAL/METHODS:
Retrospective review of 100 abdominal computed tomographic scans. RESULTS: In 6
patients small pancreatic lipomas were found. There was no predominance in
location or gender. The lipomas measured between 4 and 12 mm. All lipomas were
incidental findings unrelated to patients' symptoms. CONCLUSIONS: Pancreatic
lipomas seem to be quite a common finding and can be found in 6% of patients
undergoing abdominal CT. Radiologists should be aware of this finding to
establish proper differential diagnosis.
PMID- 25126152
TI - Uncovering health literacy: Developing a remotely administered questionnaire for
determining health literacy levels in health disparate populations.
AB - INTRODUCTION: Low health literacy contributes to health disparities. We sought to
develop and evaluate a remotely administered tool to measure health literacy in
health disparate populations. The basic research design involved asking the
remotely administered questions in conjunction with an existing and valid measure
of health literacy, the S-TOFHLA, to a non-representative convenience sample of
individuals drawn from lower income communities. The measures of the remotely
administered questions were then correlated with the results of the S-TOFHLA to
determine if there was a connection between the two measures. We found a
statistically significant correlation between a single question in the remotely
administered survey and the validated S-TOFHLA measure. This research supports
previous work that points to the importance of just a single remotely
administered question in terms of correspondence with the S-TOFHLA. OBJECTIVE:
Develop a questionnaire that can be remotely administered to check for Health
Literacy. METHODS: Correlation analysis is conducted between various questions
and S-TOFHLA scores to determine criterion validity. RESULTS: A single question,
"How confident are you in filling out medical forms by yourself?" outperforms
other measures in correlating with the S-TOFHLA scores. CONCLUSIONS: Further
assessment of the confidence question both in isolation and in conjunction with
other literacy identifiers should be conducted. Also, this question should be
tested against other measures of health literacy beyond the S-TOFHLA.
PMID- 25126153
TI - A Fabry-Perot Interferometry Based MRI-Compatible Miniature Uniaxial Force Sensor
for Percutaneous Needle Placement.
AB - Robot-assisted surgical procedures, taking advantage of the high soft tissue
contrast and real-time imaging of magnetic resonance imaging (MRI), are
developing rapidly. However, it is crucial to maintain tactile force feedback in
MRI-guided needle-based procedures. This paper presents a Fabry-Perot
interference (FPI) based system of an MRI-compatible fiber optic sensor which has
been integrated into a piezoelectrically actuated robot for prostate cancer
biopsy and brachytherapy in 3T MRI scanner. The opto-electronic sensing system
design was minimized to fit inside an MRI-compatible robot controller enclosure.
A flexure mechanism was designed that integrates the FPI sensor fiber for
measuring needle insertion force, and finite element analysis was performed for
optimizing the correct force-deformation relationship. The compact, low-cost FPI
sensing system was integrated into the robot and calibration was conducted. The
root mean square (RMS) error of the calibration among the range of 0-10 Newton
was 0.318 Newton comparing to the theoretical model which has been proven
sufficient for robot control and teleoperation.
PMID- 25126154
TI - Steering Fluorescence Emission with Metal-Dielectric-Metal Structures of Au, Ag
and Al.
AB - Directional control over fluorescence emission is important for improving the
sensitivity of fluorescence based techniques. In recent years, plasmonic and
photonic structures have shown great promise in shaping the spectral and spatial
distribution of fluorescence, which otherwise is typically isotropic in nature
and independent of the observation direction. In this work we have explored the
potential of metal-dielectric-metal (MDM) structures composed of Au, Ag or Al in
steering the fluorescence emission from various probes emitting in the NIR,
Visible or UV/blue region. We show that depending on the optical properties of
the metal and the thickness of the dielectric layer, the emission from randomly
oriented fluorophores embedded within the MDM substrate is transformed into
beaming emission normal to the substrate. Agreement of the observed angular
emission patterns with reflectivity calculations reveals that the directional
emission is due to the coupling of the fluorescence with the electromagnetic
modes supported by the MDM structure.
PMID- 25126155
TI - Sensing Reversible Protein-Ligand Interactions with Single-Walled Carbon Nanotube
Field-Effect Transistors.
AB - We report on the reversible detection of CaptAvidin, a tyrosine modified avidin,
with single-walled carbon nanotube (SWNT) field-effect transistors (FETs)
noncovalently functionalized with biotin moieties using 1-pyrenebutyric acid as a
linker. Binding affinities at different pH values were quantified, and the
sensor's response at various ionic strengths was analyzed. Furthermore, protein
"fingerprints" of NeutrAvidin and streptavidin were obtained by monitoring their
adsorption at several pH values. Moreover, gold nanoparticle decorated SWNT FETs
were functionalized with biotin using 1-pyrenebutyric acid as a linker for the
CNT surface and (+/-)-alpha-lipoic acid linkers for the gold surface, and
reversible CaptAvidin binding is shown, paving the way for potential dual mode
measurements with the addition of surface enhanced Raman spectroscopy (SERS).
PMID- 25126156
TI - Effects of van der Waals Interactions in the Adsorption of Isooctane and Ethanol
on Fe(100) Surfaces.
AB - van der Waals (vdW) forces play a fundamental role in the structure and behavior
of diverse systems. Because of development of functionals that include nonlocal
correlation, it is possible to study the effects of vdW interactions in systems
of industrial and tribological interest. Here we simulated within the framework
of density functional theory (DFT) the adsorption of isooctane (2,2,4
trimethylpentane) and ethanol on an Fe(100) surface, employing various exchange
correlation functionals to take vdW forces into account. In particular, this
paper discusses the effect of vdW forces on the magnitude of adsorption energies,
equilibrium geometries, and their role in the binding mechanism. According to our
calculations, vdW interactions increase the adsorption energies and reduce the
equilibrium distances. Nevertheless, they do not influence the spatial
configuration of the adsorbed molecules. Their effect on the electronic density
is a nonisotropic, delocalized accumulation of charge between the molecule and
the slab. In conclusion, vdW forces are essential for the adsorption of isooctane
and ethanol on a bcc Fe(100) surface.
PMID- 25126157
TI - Stereotactic Ablative Radiotherapy (SABR): Impact on the Immune System and
Potential for Future Therapeutic Modulation.
AB - Stereotactic ablative radiotherapy (SABR) has been demonstrated to provide
excellent local control in several malignancies. Recent reports have suggested
that this ablative dose may impact disease outside of the radiated area.
Furthermore, these studies have implicated immune modulation as the primary
mechanism of disease response outside the irradiated area. More specifically, T
cell stimulation and tumor necrosis factor-alpha modulation following high dose
irradiation have been suggested as the responsible components of this phenomenon.
In addition, the "abscopal effect" may play a role in disease response outside of
the radiated area. We review the current literature regarding the effects of
ablative radiation therapy, the potential for immune modulation from it, and the
mechanisms of the distant effects it elicits.
PMID- 25126158
TI - Signal transductions and nonalcoholic fatty liver: a mini-review.
AB - Nonalcoholic fatty liver disease (NAFLD) is a common liver disease, and the
incidence increases year by year. The pathogenesis of NAFLD is correlated with
insulin resistant (IR), and oxidative stress which induces varied inflammatory
cytokines (TNF-alpha, IL-1, IL-6, etc). Different signal transductions such as
MAPK, NF-kappaB, AMPK, JAK2/STAT3, PPAR, PI3K/Akt, TLR were activated by the
pathogenic factors to regulate correlative reactions. Thus, in-depth study of the
signal transductions will probably provide new suitable solutions for the
prevention and therapy of NAFLD.
PMID- 25126159
TI - Oropharyngeal airway changes after rapid maxillary expansion: the state of the
art.
AB - The aim of this article is to elucidate the state of the art about how rapid
maxillary expansion (RME) produces changes in the oropharyngeal airways in terms
of CBCT (Cone Beam Computed Tomography) data during the growth period, according
to the available literature. Electronic search was done from January 2009 to
April 2014 on PubMed and Scopus databases; in addition manual search was
conducted as well. According to keywords, seven papers were eligible for our
purpose, but definitely five papers were selected in agreement with the
inclusion/exclusion criteria. The current literature suggests that the potential
relationship between RME and oropharyngeal airway changes is still unclear. In
fact, although the pharyngeal airway changes after the rapid palatal expansion
are evident clinically, current orthodontic literature does not provide
conclusive evidence about the nature of this relationship.
PMID- 25126160
TI - MicroRNA-132 silencing decreases the spontaneous recurrent seizures.
AB - OBJECTIVE: This study aimed to investigate the role of microRNA-132 in the
epileptogenesis. METHODS: Antagomir-132 (Ant-132) was used to silence the
expression of miR-132 and non-targeting scrambled sequence (Scr) as a control.
Rats were randomly divided into ant-132 group and Scr group in which rats were
pretreated with An-132 and Scr, respectively, and then induced temporal lobe
epilepsy (TLE) by Li-Pilo. Behavioral observation was done, and results showed
the changes in spontaneous recurrent seizures in the chronic phase between two
groups. Bax and Bcl-2 were detected aiming to evaluate the neuronal apoptosis.
NPY staining was done to investigate the mossy fiber sprouting (MFS). Golgi
staining was used to assess the changes in the dendritic morphology. RESULTS: Our
study showed that ant-132 induced miR-132 silencing in rats could increase the on
set epilepsy threshold and suppress the numbers of spontaneous recurrent
seizures. The number of apoptotic neurons and MFS reduced after miR-132
silencing. In addition, the dendrites of neurons were highly suppressed in the
CA3 region of the hippocampus. CONCLUSIONS: miR-132 silencing suppresses the
spontaneous seizures. The better outcome may result from the neuroprotective
effect and the inhibition of MFs-CA3 pathway following miR-132 silencing. Thus,
miR-132 may serve as a potential target for the development of anti-epileptic
drugs.
PMID- 25126161
TI - TREM-1 as a potential therapeutic target in neonatal sepsis.
AB - OBJECTIVE: Bacterial sepsis in neonates is associated with elevated morbidity and
mortality. A role for the pro-inflammatory Triggering Receptor Expressed on
Myeloid cells-1 (TREM-1) is suspected in the innate immune response to bacteria,
but little is known about its activities in infants. To begin exploring the
feasibility of treating neonatal sepsis by blocking leukocyte TREM-1, we compared
TREM-1 membrane expression and mRNA in newborns without clinical or
microbiological evidence of infection, to that of healthy adults. The
functionality of pro-inflammatory reactions in leukocyte TREM-1 of newborns was
also evaluated. METHODS: Twenty term newborns were enrolled in this study and
cord blood samples were collected at birth. For comparison, peripheral blood
specimens were collected from 20 healthy adults (control adult, CA). The
expression of TREM-1 protein and mRNA in leukocytes was detected with flow
cytometry and real-time qPCR, respectively. Whole cord blood was also stimulated
by Escherichia coli or blocked by the TREM-1-specific peptide LP17 to identify
changes in the secretion of pro-inflammatory cytokines interleukin (IL)-6, IL-8,
and tumor necrosis factor (TNF)-alpha, as well as soluble TREM-1 (sTREM-1) using
enzyme linked immunosorbent assay (ELISA). RESULTS: Mean fluorescence intensity
(MFI) of TREM-1 on leukocytes of newborns appeared comparable to healthy adults
[monocytes: 37.5 +/- 6.7 vs. 37.6 +/- 8.7; polymorphonuclear cells (PMNs): 32.9
+/- 6.6 vs. 33.6 +/- 5.8]. However, the percentage of PMNs positive for TREM-1
was lower in newborns than in healthy adults (82.3 +/- 7.1 vs. 98.6 +/- 4.8; P <
0.01); the percentage of TREM-1-positive CD14-positive monocytes was comparable
to that of healthy adults (97.1 +/- 8.3 vs. 97.5 +/- 7.4). Exposure of cord blood
to E. coli resulted in increased secretion of IL-6, IL-8, TNF-alpha, and sTREM-1.
In contrast, the concentrations of IL-6, IL-8, and TNF-alpha decreased by a
minimum of 15% when TREM-1 was blocked by LP17 then exposed to E. coli, versus E.
coli alone. In addition, the concentration of sTREM-1 was positively correlated
with the levels of TNF-alpha (r = 0.519, P < 0.05), IL-6 (r = 0.507, P < 0.05),
and IL-8 (r = 0.538, P < 0.05). CONCLUSIONS: Healthy newborns exhibit expression
of TREM-1 on monocytes similar to that in healthy adults, and most PMNs express
TREM-1 at the newborn stage. Detection of sTREM-1 in neonatal peripheral blood
should be further investigated as a potential method for the diagnosis of
neonatal infection. Finally, blocking the TREM-1 signal transduction pathway may
reduce inflammatory responses of neonate leukocytes and thereby provide a new
strategy for treatment of neonatal infection.
PMID- 25126162
TI - Camk2b protects neurons from homocysteine-induced apoptosis with the involvement
of HIF-1alpha signal pathway.
AB - In our previous study using iTRAQ technique we found that the level of calmodulin
dependent protein kinase 2b (Camk2b) was lower in rats with hyperhomocysteinemia.
We presumed that Camk2b might be involved in homocysteine-induced apoptosis and
tried to explore its role in this study through the transfection with Camk2b
gene. Results showed that neurons of HHcy group had lower activity measured by
MTT, higher percentage of apoptotic neurons, lower expression levels of Camk2b
mRNA and protein than those in normal group. Neurons with overexpression of
Camk2b (Camk2b group) had lower percentage of apoptosis and higher activity than
those in control group. After exposure to 2-Methoxyestradiol, the activity of
neurons with overexpression of Camk2b was suppressed with more apoptotic cells
observed. The expressions of BCL2, eNOS, EP300 and EPO were all elevated at both
mRNA and protein levels in neurons of CamK2b group compared with other three
groups. Thus, Camk2b protects neurons from Homocysteine-induced apoptosis with
the involvement of HIF-1alpha signal pathway.
PMID- 25126163
TI - Radiographical and clinical evaluation of critical size defects in rabbit
calvaria filled with allograft and autograft: a pilot study.
AB - Regeneration of resorbed edentulous sites can be induced by bone grafts from the
subject himself and/or by the use of biomaterials. At present, there has been an
extensive search for biomaterials that are evaluated by artificially creating one
or more critical defects. The aim of this work was to clinically and
radiographically analyze bone formation by the use of some biomaterials in
artificially created defects in the parietal bone of rabbits. Six rabbits were
used, creating defects of 8 mm in diameter in parietal bones. One defect was
maintained with coagulum only, and in others, freeze-dried bone allograft (FDBA),
autologous bone, and a combination of autologous bone with FDBA respectively,
were added. Animals were sacrificed at 15-90 days with 2 weeks interval each, and
calvaria were analyzed macroscopically, measuring by digital caliper the lack of
filling at the surface of defects, identifying limits at anteroposterior and
coronal view, realizing a digital photograph register of their external surfaces.
This was subsequently evaluated radiographically by occlusal film radiography
used to quantify its density through software. In conclusion, autologous bone
showed the best behavior, clinically as well as radiographically. However, FDBA
is a good option as an alternative to autologous bone as its behavior was
slightly lower over time. The combination of autologous bone and FDBA in the same
defect showed results considerably inferior to grafts used separately. Low
radiopacity and clear limits were observed through time for the control coagulum
filled defect.
PMID- 25126164
TI - Serum M30 and M65 levels and effects of Ankaferd blood stopper in cerulein
induced experimental acute pancreatitis model in rats.
AB - BACKGROUND AND AIM: The incidence of acute pancreatitis is increasing recently.
The aim of this study is to investigate the effect of Ankaferd Blood Stopper
(ABS) on experimental model of cerulein induced acute pancreatitis in rats.
MATERIALS AND METHODS: Forty Wistar Albino rats were divided into five groups.
Group 1: Sham (n = 8), Group 2: Control group (n = 8), Group 3: Treatment group
(n = 8), Group 4: Prophylaxis group (n = 8), Group 5: Prophylaxis treatment group
(n = 8). Any practice was not administered to Group 1. Rats were treated with
either 1 ml ABS or 1 ml saline via intraperitoneal route before and after
inducing acute pancreatitis. Pancreatic tissues were examined
histopathologically. Amylase, cytokines (tumor necrosis factor-alpha and
interleukin-1beta), and markers of apoptosis (M30 and M65) were also measured in
blood samples. Immunohistochemical staining was performed with caspase 3
antibody. RESULTS: We found a statistically significant improvement in
histopathological scores in treatment group and prophylaxis group compared with
controls. In treatment group, M30 and M65 levels were lower when compared with
controls. In prophylaxis group, there was not a statistically significant
difference in M30 levels, but M65 levels were lower when compared with controls.
CONCLUSION: In this experimental acute pancreatitis model, we found high
histopathological healing effects of ABS treatment and also prophylaxis. ABS
treatment and prophylaxis reduced apoptosis.
PMID- 25126166
TI - FRAS1 knockdown reduces A549 cells migration and invasion through downregulation
of FAK signaling.
AB - Distal metastasis is the major cause of death for the vast majority of lung
cancer patients. Many extracellular matrix (ECM)-related molecules are proposed
to be associated with the migration and invasion of cancer cells. FRAS1 encodes
an ECM protein, however, little is known about its function on tumorigenesis and
metastasis of lung cancer. In this work, FRAS1 was silenced by shRNA in non-small
cell lung cancer (NSCLC) A549 cell line. The capacities of A549 cells to migrate
and invade were decreased markedly after FRAS1 knockdown. The shRNA knockdown of
FRAS1 was found to be specific and had no effect on A549 cells proliferation.
Western blot experiments demonstrated that FRAS1 knockdown inhibited FAK
signaling but not Src signaling. Overall, we found that FRAS1 knockdown reduces
A549 cells migration and invasion ability through downregulation of FAK
signaling.
PMID- 25126165
TI - Celastrol may have an anti-atherosclerosis effect in a rabbit experimental
carotid atherosclerosis model.
AB - BACKGROUND: Celastrol may have an anti-atherosclerosis effect. This study aimed
to investigate if celastrol had an anti-AS effect using a rabbit experimental
carotid atherosclerosis model. METHODS: Forty male Japanese white rabbits were
divided into the sham group (normal diet), the model group (high fat diet), the
group treated with celastrol (high fat diet) and the group treated with
atorvastatin (high fat diet) randomly. The rabbits fed a high fat diet underwent
balloon injury of the right common carotid artery and were treated with dimethyl
sulfoxide (DMSO) (the model group, 3.5 ml/kg/d), celastrol and its dissolvent
DMSO (the celastrol group, 1 mg/kg/d and 3.5 ml/kg/d) and atorvastatin and its
dissolvent DMSO (the atorvastatin group, 2.5 mg/kg/d and 3.5 ml/kg/d) for 12
weeks by gavage. RESULTS: The ratio of the plaque area and the arterial wall
cross-section area in the celastrol group was significantly less than the model
group (P < 0.001), and there was no significant difference compared with the
atorvastatin group. The serum level of LDL-C of the celastrol group was
significantly lower than the model group (P = 0.014), and there was no
significant difference compared with the atorvastatin group. The expression of
VEGF in the celastrol group was significantly less compared with the model group
(P = 0.014), whereas the expression of VEGF in the atorvastatin group and the
model group showed no significant differences. CONCLUSION: Our findings suggest
that celastrol effectively reduced the plaque ratio, decreased the serum levels
of LDL and downregulated the expression of VEGF, suggesting an anti-AS effect of
celastrol.
PMID- 25126167
TI - Ameliorating effects of CAPE on oxidative damage caused by pneumoperitoneum in
rat lung tissue.
AB - We investigated the biochemical and histopathological effects of caffeic acid
phenethyl ester (CAPE) against oxidative stress causing lung injury induced by
pneumoperitoneum. Twenty-eight rats were selected at random and seven rats were
assigned to each of the following groups. The control group (S) was subjected to
a sham operation without pneumoperitoneum. The other groups were subjected to CO2
pneumoperitoneum 15 mmHg for 60 min. The laparoscopy group (L) had no additional
drugs administered, the laparoscopy + alcohol (LA) group had 1 ml of 70% ethyl
alcohol administered 1 h before the desufflation period, and the laparoscopy +
CAPE (LC) group had CAPE administered at 10 MUmol/kg 1 h before the desufflation
period. The total oxidative status levels of lung and plasma were significantly
increased in the LA group as compared with the LC and S group. When the LC group
was compared with the L group, there was a decrease in the level of total oxidant
status and increase in the levels of total antioxidant status and paraoxonase in
lung tissue. The level of total antioxidative status in the S group was increased
compared with the L group in lung tissue and bronchoalveolar lavage fluid. TNF
alpha and IL-6 were found significantly elevated in the L group compared with the
LC and S groups in bronchoalveolar lavage fluid. There was a similar increase in
plasma levels of IL-6. These results were supported by histopathological
examination. CAPE was found to considerably reduce oxidative stress and
inflammation induced by pneumoperitoneum.
PMID- 25126168
TI - L-3-n-butylphthalide improves cognitive impairment of APP/PS1 mice by
BDNF/TrkB/PI3K/AKT pathway.
AB - L-3-n-butylphthalide (L-NBP), an extract from seeds of Apium graveolens Linn
(Chinese celery), has been shown to have neuroprotective effects on cerebral
ischemic, vascular dementia and amyloid-beta (Abeta)-induced animal models by
inhibiting oxidative injury, neuronal apoptosis and glial activation, regulating
amyloid-beta protein precursor (AbetaPP) processing and reducing Abeta
generation. The objective of this study was to investigate the effects of L-3-n
butylphthalide on memory impairment and the expression of brain neurotrophic
derived factor (BNDF), kinaseB (TrkB), phosphatidylinositol 3 kinase (PI3K) and
Akt in APP/PS1 double transgenic mouse models. APP/PS1 double transgenic mice
were administered 30 mg/kg*d L-NBP and 10 mg/kg*d L-NBP for one month. The
learning and memory ability were studied using the water maze test. Protein
expression and transcript levels of genes in the mice hippocampus were evaluated
using western blot and quantitative reverse transcription-polymerase chain
reaction (qRT-PCR), respectively. The results demonstrated that both 30 mg/kg*d L
NBP and 10 mg/kg*d L-NBP doses of L-NBP significantly increased memory capability
and the expression of hippocampal BDNF/TrkB/PI3K/AKT in mice The results
suggested that L-NBP treatment may reverse memory impairment in APP/PS1
transgenic mice, and BDNF/TrkB/PI3K/AKT, may be involved in this process.
PMID- 25126169
TI - Occlusive barriers in combination with particulate Bio-Oss(r) graft: a pilot
study on rabbit calvaria.
AB - The aim of this study was to histologically evaluate the potential for vertical
bone augmentation of the Bio-Oss(r) graft compared to a blood clot in conjunction
with an occlusive barrier in the rabbit calvaria defect model. Metallic dome
shaped barriers with 4.5 mm width and 3.5 mm height were positioned in six adult
rabbit skulls. At the right side, the barrier was filled with Bio-Oss(r), and the
left side was filled with a blood clot. After a healing period of three months,
the animals were sacrificed, and the samples were prepared for histological and
histomorphometric analyses. The total mineralized area (TMA) as well as the newly
formed bone (NBA) was calculated as the percentage of the bone augmentation
inside the metallic barriers, and parametric statistical analysis was used to
describe the findings. The samples with blood clots exhibited significantly less
TMA formation than the Bio-Oss(r) group. However, the difference in the amount of
NBA was not statistically significant. Furthermore, the Bio-Oss(r) specimens
exhibited remaining graft particles within the sample. In conclusion, the
barriers filled with Bio-Oss(r) exhibited significantly higher TMA than those
with only blood clots, and the remaining Bio-Oss(r) particles were integrated
into newly formed bone tissue to fill the spaces and promote a greater volume
than the samples from the blood clot groups.
PMID- 25126170
TI - Antibacterial activity of leaf essential oil and its constituents from Cinnamomum
longepaniculatum.
AB - Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 and Salmonella
enteritidis CMCC (B) 50041, were used in the antibacterial tests of Cinnamomum
longepaniculatum leaf essential oil and its five chemical constituents. The
effect of 1, 8-cineole on the ultrastructural structure of the bacteria (S.
aureus and E. coli) was also investigated by transmission electron microscopy.
The C. longepaniculatum leaf essential oil and the five chemical constituents
showed variable levels of inhibition. Their MIC ( minimum inhibitory
concentration ) and MBC (minimal bacteriocidal concentration) values were all in
the range of 0.781 uL/mL~6.25 uL/mL and 0.781 uL/mL~12.5 uL/mL respectively
except gamma-terpinene. The MIC values of gamma-terpinene against E. coli and S.
aureus were all higher than 50 uL/mL, but the MIC and MBC values of gamma
terpinene against S. enteritidis was only 3.125 uL/mL. Among them, alpha
terpineol possessed the best antibacterial activity. Under the transmission
electron microscope, cell size of treated E. coli decreased, cell wall and cell
membrane ruptured, and nucleoplasm was reduced and gathered onto the side. After
the S. aureus was treated with 1, 8-cineole, the cell size and shape were damaged
and nucleus cytoplasm was concentrated or reduced or agglomerated on the side.
These results suggest that C. longepaniculatum leaf essential oil and its
constituents have excellent antibacterial activities, the antibacterial mechanism
of 1, 8-cineole against E. coli and S. aureus might attributable to its
hydrophobicity.
PMID- 25126172
TI - Methylation status of promoter 1 region of GDNF gene in human glioma cells.
AB - OBJECTIVE: This study aimed to investigate the methylation status of promoter 1
region of glial cell line-derived neurotrophic factor (GDNF) in human glioma
cells and to explore the effect of GDNF methylation on the expression of GDNF in
glioma. METHODS: GDNF gene mutation was detected by sequencing in 10 patients
with glioma and 5 healthy controls. Bisulfite modification for analysis of DNA
methylation was done to detect the methylation status of promoter 1 region of
GDNF in 20 patients with glioma (10 with poorly differentiated and 10 with well
differentiated) and 5 healthy controls. RESULTS: There was no mutation at the
promoter 1 region of GDNF gene in glioma. The incidence of methylation of GDNF
gene at the promoter 1 region in healthy control, patients with poorly
differentiated glioma and those with well differentiated glioma was 72.25%,
86.25% and 86.75%. The incidence of GDNF methylation in glioma was significantly
higher than that in the normal brain (P<0.05); while there was no significant
difference between well differentiated glioma and poorly differentiated glioma.
CONCLUSIONS: Hypermethylation occurs in the promoter 1 region of GDNF and may
influence the expression of GDNF in glioma.
PMID- 25126171
TI - Accuracy of pulse oximeter perfusion index in thoracic epidural anesthesia under
basal general anesthesia.
AB - OBJECTIVE: To observe the change of PVI after thoracic epidural block on the
basis of general anesthesia. METHODS: In 26 patients undergoing elective upper
abdominal operations, changes of SVI, PVI, SVV, PPV and CVP were monitored
immediately before and 10 minutes after T8-9 thoracic epidural anesthesia on the
basis of general anesthesia. The definition was that patients with DeltaSVI
greater than 10% belonged to response group to epidural block. RESULTS: Before
epidural block, the PVI, SVV and PPV baseline values in patients of response
group were significantly higher than those in patients of non-response group.
PVI, SVV and PPV after epidural block were significantly higher than immediately
before epidural block (P < 0.001). PVI, SVV and PPV baseline values immediately
before epidural block were positively correlated with DeltaSVI; the correlation
coefficients were 0.70, 0.71 and 0.63, respectively, P <= 0.001. The optimal
critical values for PVI, SVV and PPV to predict response to T8-9 gap epidural
block under general anesthesia were 16% (sensitivity 80%, specificity 92%), 13%
(sensitivity 90%, specificity 62%) and 12% (sensitivity 90%, specificity 77%),
respectively. CONCLUSION: PVI can be used as a noninvasive indictor to monitor
volume change after thoracic epidural block on the basis of general anesthesia.
PMID- 25126173
TI - Rosiglitazone accentuates the adipogenesis of hemangioma-derived mesenchymal stem
cells induced by adipogenic media.
AB - Hemangioma-derived mesenchymal stem cells (Hem-MSCs) expressed PPAR-gamma, the
key transcription factor in adipogenesis. We supposed that rosiglitazone, the
agonist of PPAR-gamma, may promote the adipogenesis of Hem-MSCs. In this study,
MSCs were isolated from proliferating hemangioma. Four groups were set up, which
were Group A (DMEM-LG/10% FBS), Group B (1 MUM rosiglitazone + DMEM-LG/10% FBS),
Group C (adipogenic media), and Group D (1 MUM rosiglitazone + adipogenic media).
Cells were cultured in the medium above. On the day 7 and 14, Oil Red "O"
staining and Western blot were performed to detect the cytoplasmic lipid and
perilipin A in the cells. The results showed that cytoplasmic lipid appeared in
Group C and D, and no cytoplasmic lipid in Group A and B on the day 7 and 14.
Analysis of Oil Red "O" staining showed the area of staining in Group D was
significantly larger than that in Group C. Analysis of western blot showed no
expression of perilipin A in Group A and B, and upregulated expression in Groups
C and D, with the greater upregulation in Group D. In conclusion, our study
demonstrated that rosiglitazone promoted the adipogenesis of Hem-MSCs initiated
by adipogenic media via the activation of PPAR-gamma pathway. The results may put
forward the possibility of treating hemangioma via PPAR-gamma pathway.
PMID- 25126174
TI - Confirming the brain death diagnosis using brain CT angiography: experience in
Tokat State Hospital.
AB - OBJECTIVE: Fourteen brain death cases diagnosed in Mart 2012-May 2013 period in
Tokat State Hospital were studied retrospectively. CT angiography experience
about those cases was shared, and use of CT angiography in confirmation of brain
death was discussed. MATERIAL AND METHODS: All 14 cases were patients on
mechanical ventilator, who did not respond to medical and surgical treatments at
intensive care unit and were diagnosed clinically with brain death. All of these
patients had CT angiography as a confirmatory test using a 4-slice CT scanner in
Radiology department in Tokat State Hospital. FINDINGS: Six of the patients were
female and eight were male. All of them were referred from intensive care unit
and had clinical brain death diagnosis before CT angiography. In the evaluation
of CTA, four-point scoring involving opacification loss in both ICVs and cortical
segments of MCA was used. CTA examinations confirmed brain death diagnoses in all
patients who had clinical brain death diagnoses, and no confliction between CTA
findings and clinical diagnoses was observed. CONCLUSION: Demonstrating the lack
of cerebral circulation is a necessity for confirmation of brain death diagnosis.
While conventional angiography remains the standard method, CTA emerged as an
alternative method. In parallel to increase in prevalence of organ implants, CTA,
a fast and efficient method, has been increasingly used in confirmation of brain
death diagnoses.
PMID- 25126175
TI - A novel approach to locate renal artery during retroperitoneal laparoendoscopic
single-site radical nephrectomy.
AB - OBJECTIVE: To verify the feasibility and safety of retroperitoneal
laparoendoscopic single-site radical nephrectomy and assess the value of our
proposed approach to search for renal artery. METHODS: A total of 60 cases of
retroperitoneal laparoendoscopic single-site radical nephrectomy were performed
using our homemade single-port multi-channel device. An incision of 5-6 cm was
cut forward from the posterior axillary line under the lower margin of the 12th
rib, and a single-port multi-channel device comprised of two control rings and a
No. 7 glove was placed into the incision. Retroperitoneal laparoendoscopic single
site radical nephrectomy was then performed via locating renal artery through
muscle and ligament on the posterior abdominal. RESULTS: The 60 cases were all
successful. None of the 60 patients developed surgical complications. CONCLUSION:
The application of homemade device is safe and feasible. Our proposed method is
of greater practical significance for the relatively narrow operating space in
retroperitoneal laparoendoscopic single-site surgery.
PMID- 25126176
TI - Primary malignant melanoma of the lung: a case report.
AB - Primary malignant melanoma of the lung is a very rare disease with about 40 cases
reported in English literature. We report a 49-year-old female with history of 2
month chest pain who was revealed to have a peripheral lung mass in left upper
lobe by chest CT scan. Left upper lobectomy was performed and post-operative
pathology revealed to be primary malignant melanoma of the lung. 4 months after
operation, a node in right breast was found by patient herself and needle
aspiration biopsy revealed to be breast cancer. The patient refused any
diagnostic and therapeutic procedure and died of extensive metastasis 3 months
later. Primary malignant melanoma of the lung is highly malignant disease with
poor prognosis in most patients.
PMID- 25126177
TI - Human umbilical cord mesenchymal stromal cells suppress MHC class II expression
on rat vascular endothelium and prolong survival time of cardiac allograft.
AB - BACKGROUND: Human umbilical cord mesenchymal stromal cells (UC-MSCs) have low
immunogenicity and immune regulation. To investigate immunomodulatory effects of
human UC-MSCs on MHC class II expression and allograft, we transplanted heart of
transgenic rats with MHC class II expression on vascular endothelium. METHODS: UC
MSCs were obtained from human umbilical cords and confirmed with flow cytometry
analysis. Transgenic rat line was established using the construct of human MHC
class II transactivator gene (CIITA) under mouse ICAM-2 promoter control. The
induced MHC class II expression on transgenic rat vascular endothelial cells
(VECs) was assessed with immunohistological staining. And the survival time of
cardiac allograft was compared between the recipients with and without UC-MSC
transfusion. RESULTS: Flow cytometry confirmed that the human UC-MSCs were
positive for CD29, CD44, CD73, CD90, CD105, CD271, and negative for CD34 and HLA
DR. Repeated infusion of human UC-MSCs reduced MHC class II expression on
vascular endothelia of transplanted hearts, and increased survival time of
allograft. The UC-MSCs increased regulatory cytokines IL10, transforming growth
factor (TGF)-beta1 and suppressed proinflammatory cytokines IL2 and IFN-gamma in
vivo. The UC-MSC culture supernatant had similar effects on cytokine expression,
and decreased lymphocyte proliferation in vitro. CONCLUSIONS: Repeated
transfusion of the human UC-MSCs reduced MHC class II expression on vascular
endothelia and prolonged the survival time of rat cardiac allograft.
PMID- 25126178
TI - Kinetic analysis of the immunity in a pregnant patient infected with avian
influenza H7N9.
AB - BACKGROUND: Human infection with avian influenza A H7N9 has emerged in China
since February, 2013. The immunologic changes in pregnant women infected with
H7N9 are not known. OBJECTIVE: To report the clinical data and kinetic changes of
immunity in a pregnant woman infected with H7N9 virus in Zhenjiang, Jiangsu,
China. METHODS: The clinical data were collected and immunity status was
monitored in this patient. RESULTS: H7N9 virus became undetectable in sputum from
14 days since onset of symptoms after effective antiviral therapy with
oseltamivir and symptomatic/supporting treatments. The symptoms and signs in this
patient gradually improved from 15 days since onset of symptoms. Peripheral
lymphocytes initially decreased and gradually increased. The percentage of CD4+ T
cells increased since 16 days after onset of symptoms. The kinetic changes of
cytokines including IFN-gamma, IFN-alpha, TNF-alpha, IL-10 and TGF-beta1 matched
the development and recovery of illness. Her family members, including her
parents exposed to H7N9 positive materials in poultry market, were H7N9 negative.
CONCLUSIONS: Our results indicate that pregnant women are susceptible to H7N9
virus and H7N9 infection in pregnant women is curable without significant impact
on fetus. Kinetic changes of pro-inflammatory and anti-inflammatory cytokines
play a role in the pathogenesis and clinical outcome in the pregnant patient with
H7N9 infection.
PMID- 25126179
TI - Application status of blood constituents during massive blood transfusion in some
regions of China.
AB - OBJECTIVE: This study aims to learn about the current situation of surgical
massive blood transfusion in China's Class III general hospitals, which could
provide the basis for the formulation of guidelines on massive blood transfusion.
METHODS: A multicenter retrospective research on the application status of blood
constituents during massive blood transfusion was conducted and a comparative
analysis on the distribution of the population infused with other blood
constituents and the transfusion volume at different periods of time when red
blood cells are infused in different units within 24 hours as well as on the
blood applied for both the death group and survival group was made in this study.
RESULTS: In China, during massive blood transfusion the ratio of the dosage of
fresh frozen plasma to the dosage of red blood cell suspension reached 1:1-2,
while the dosage of platelet and cryocepitate appeared to be very small.
CONCLUSION: During massive blood transfusion, clinicians in 20 Chinese hospitals
paid more attention to the infusion of fresh frozen plasma while making the
infusion of red blood cells. However, they paid little attention to the
supplement of platelet and cryocepitate.
PMID- 25126180
TI - Presence of FOXP3(+)Treg cells is correlated with colorectal cancer progression.
AB - The transcription factor FOXP3 is specifically expressed in regulatory T (Treg)
cells and appears to mediate immune surveillance. Indeed, FOXP3(+)Treg cells have
been linked to disease pathogenesis, including some cancers. This study
investigated the presence of FOXP3(+)Treg cells in colorectal cancer and the
relationship of FOXP3 expression with clinicopathological features of colorectal
cancer. Immunohistochemistry was used to detect expression of FOXP3 in 63 samples
of colorectal cancer and 20 samples of healthy colorectal tissue; flow cytometry
was used to detect FOXP3(+)Treg cells in peripheral blood. FOXP3 was more
commonly expressed in colorectal cancer tissues than in normal colorectal tissues
(P < 0.05). Similarly, the percentage of FOXP3(+)Treg cells in the peripheral
blood was higher in patients with colorectal cancer than in control individuals
(P < 0.05). The expression of FOXP3 was positively correlated with gender, Dukes
staging, and lymph node metastasis. Further, expression increased with the
increasing degree of malignancy (P < 0.05). Thus, FOXP3 expression may represent
a valuable index in evaluating the degree of malignancy, clinicopathologic
staging, and lymph node metastasis in colorectal cancer. Further, detection of
FOXP3(+)Treg cells may be useful in predicting invasion, metastasis, and
prognosis of patients with colorectal cancer.
PMID- 25126181
TI - Aberrant sonic hedgehog signaling pathway and STAT3 activation in papillary
thyroid cancer.
AB - The sonic hedgehog (SHH) and STAT3 signaling pathways play important roles during
carcinogenesis with possible interaction. To determine the association of the
activation of SHH signaling pathway and STAT3 pathway in carcinogenesis of human
papillary thyroid cancer (PTC), we examined the expression of SHH signaling
pathway molecules including SHH, Patched (PTCH), Smoothened (SMO) and GLI1
(glioma-associated oncogene homolog 1), as well as p-STAT3 (phosphorylation at
Tyr705) by immunohistochemistry in 164 cases of PTC. In PTC, 70.12%, 64.02%,
68.90%, 64.02%, and 56.71% and in the adjacent normal thyroid tissues, 18.29%,
18.90%, 26.83%, 14.63%, and 10.98% of the specimens stained positive for SHH,
PTCH, SMO, GLI1, and p-STAT3, respectively. Significant difference were found for
the positive rate of SHH, PTCH, SMO, and GLI1 as well as p-STAT3 expression
between PTC and adjacent normal thyroid tissues. There was a high accordance rate
between SHH, PTCH, SMO, and GLI1 expression and all of them positively correlated
with larger tumor size, the presence of ETE and LNM, and higher TNM stage. P
STAT3 expression positively correlated with the presence of ETE and LNM, and
higher TNM stage but not age, gender, tumor size of the PTC patients. Signifi
cant positive correlation between p-STAT3 and SHH, PTCH, SMO and GLI expression
was found in PTC. These findings suggest that the SHH and STAT3 signaling
pathways are frequently activated in PTC, interact with each other and may
therefore be indicators for prognosis or potential targets for therapy against
PTC.
PMID- 25126183
TI - Serum endocan levels in patients with chronic liver disease.
AB - BACKGROUND AND AIM: Early detection of fibrosis should be the main goal of
treatment in liver cirrhosis. Endocan, previously called endothelial cell
specific molecule-1, is expressed by endothelial cells, primarily in the lung,
liver and kidney. In this study, we aimed to examine the correlation of liver
fibrosis stage, histological activity and grade of steatosis between serum levels
of endocan in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC)
and non-alcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: This cross
sectional study includes a total of 146 subjects. 55 CHB patients, 19 CHC
patients, 38 NAFLD patients and 34 healthy controls were enrolled consecutively.
Liver biopsies were performed in all patients with chronic viral hepatitis. NAFLD
patients had either grade 2 or grade 3 steatosis on ultrasonography and elevated
liver enzymes above the upper normal limits. Serum endocan levels were assessed
from blood samples obtained at admission. RESULTS: Gender distribution was
similar among the groups (p=0.056). The mean age of the CHB patients was 45.8+/
12.1, CHC patients was 55.0+/-12.8 years, NAFLD patients was 42.8+/-10.8, while
control group was 39.4+/-13.6 years old. Patients with CHC were older than all
the others (p=0.001). Serum endocan levels were statistically significantly lower
in CHB, CHC and NAFLD groups when compared with controls. Although levels of
endocan were lower in CHB and CHC groups when compared with NAFLD group, the
difference was not statistically significant. CONCLUSION: Serum endocan
concentrations decrease in patients with liver disease. Unlike previous studies,
we showed a negative correlation between endocan levels and inflammation stage of
chronic hepatitis. However, further studies are needed to establish the
association between endocan levels, liver fibrosis and hepatic inflammation.
PMID- 25126182
TI - Association of epicardial adipose tissue, neutrophil-to-lymphocyte ratio and
platelet-to-lymphocyte ratio with diabetic nephropathy.
AB - BACKGROUND: The relationship between diabetic nephropathy, visceral adipose
tissue (VAT), and inflammation has been shown. The neutrophil-to-lymphocyte ratio
(NLR) and platelet-to-lymphocyte ratio (PLR) are simple, inexpensive, and useful
markers to determine inflammation. However, to date, in the literature, there
have been no studies demonstrating the relationship between epicardial adipose
tissue (EAT), inflammation, and albuminuria. AIMS: We aimed to investigate the
association between diabetic nephropathy, NLR, and PLR as inflammatory markers
and EAT thickness. METHODS: This was a cross-sectional study involving 200
diabetic patients. The patients were separated into three groups according to
their albuminuria levels. The NLR and PLR were calculated from a complete blood
count. EAT was measured by transthoracic echocardiography. The estimated
glomerular filtration rate (eGFR) was calculated by the modification of diet in
renal disease (MDRD) equation. RESULTS: Disease duration, EAT, creatinine, NLR,
PLR, absolute neutrophil, lymphocyte, and platelet count tended to increase with
increasing albuminuria while the eGFR decreased. When patients were separated
into two groups according to NLR and PLR medians, albuminuria levels increased
with an increase of the NLR (p = 0.003) and PLR (p = 0.009). A correlation
analysis showed that albuminuria was significantly correlated with EAT, disease
duration, creatinine, eGFR, PLR, and NLR levels. Additionally, in a binary
logistic regression analysis, EAT, NLR, and PLR were found to be independently
associated with albuminuria. CONCLUSIONS: Determining various inflammatory
cytokines and measuring abdominal VAT in diabetic patients is complex and
expensive. Simply measuring EAT and calculating NLR and PLR can predict
inflammation and albuminuria in patients with diabetes.
PMID- 25126184
TI - Clinical significance of methylation of E-cadherin and p14ARF gene promoters in
skin squamous cell carcinoma tissues.
AB - Epigenetic regulation of genes by DNA methylation contributes to cancer. The
present study sought to identify methylation changes in the promoters of E
cadherin and p14ARF, two genes with potential cancer roles promoting in skin
squamous cell carcinoma. Skin squamous cell carcinoma specimens were collected
from 40 patients and normal skin tissues were collected from 30 individuals as
controls. Promoter methylation was detected for E-cadherin and p14ARF by
methylation-specific PCR. Correlations between E-cadherin or p14ARF methylation
and clinicopathological parameters were analyzed by the Spearman rank test.
Methylation of E-cadherin (37.5%) and p14ARF (60.0%) was significantly more
common in skin squamous cell carcinoma than in normal skin tissue (10.0 and 6.7%,
respectively; P < 0.05). Additionally, E-cadherin and p14ARF methylation were
positively correlated within skin squamous cell carcinoma (r = 0.422, P = 0.007).
Furthermore, methylation of these gene promoters in skin squamous cell carcinoma
was correlated with differentiation, lymph node metastasis, and clinical stage (P
< 0.05). Aberrant methylation in promoters of E-cadherin and p14ARF may promote
occurrence and progression of skin squamous cell carcinoma.
PMID- 25126185
TI - An miR-143 promoter variant associated with essential hypertension.
AB - MicroRNAs like miR-143 are increasingly linked to disease pathogenesis. miR-143
is enriched in vascular smooth muscle, and several single nucleotide
polymorphisms have been identified in this miRNA. The aim of the current study
was to explore a potential correlation between a polymorphism in the miR-143
promoter region, rs4705342, and essential hypertension (EH). Genotyping for miR
143 rs4705342 was performed from blood samples of 156 EH patients (case group)
and 187 healthy individuals (control group) using a TaqMan assay. Participant
demographic and clinical characteristics were also collected. Logistic regression
was used to identify an association between genotype and EH, and odds ratios of
EH risk were also determined. Frequencies of the CC, CT, and TT genotypes
differed significantly between case (7.7%, 40.4%, 51.9%) and control (15.0%,
48.1%, 36.9%) groups (chi(2) = 9.400, P = 0.009). Further, the frequency of the C
allele was lower in the case group than in the control group (27.9% vs. 39.0%, P
= 0.002). Compared with those having the TT genotype, patients carrying the CC
and CT genotypes had a significantly reduced risk for EH (OR = 0.541, 95% CI =
0.351-0.834, P = 0.005), particularly for females, nonsmokers, and those not
consuming alcohol (P < 0.05). Thus, the rs4705342 polymorphism in the miR-143
appears to be associated with essential hypertension, and further study is needed
to understand the molecular mechanism producing this effect.
PMID- 25126186
TI - Responsibility and burden from the perspective of seniors' family caregivers: a
qualitative study in Shanghai, China.
AB - OBJECTIVES: This study aimed to explore the experience of seniors' family
caregivers with regarding the responsibility, burden and support needs during
caregiving in Shanghai, China. MATERIALS AND METHODS: An exploratory,
descriptive, qualitative design was used and a semi-structure interview was
conducted. A convenience sample of 11 participants in two community service
centers in Shanghai was recruited. Data saturation guided the size of the sample.
The Colaizzi method of empirical phenomenology was used for interviewing and
analyzing data obtained from 11 caregivers. RESULTS: Three major themes were
found: It is a hard work; It is my responsibility; Social support is not enough.
CONCLUSION: The findings of the study are practical and helpful for health care
providers to develop appropriate caregiver support services, to balance the
responsibility and burden of caregivers, and to consider the factors influencing
the utility of support services.
PMID- 25126187
TI - Prevalence of prostatitis-like symptoms in outpatients with four premature
ejaculation syndromes: a study in 438 men complaining of ejaculating prematurely.
AB - OBJECTIVE: To evaluate the incidence of prostatitis-like symptoms (PLS) in men
with or without PE, and the differences among the 438 outpatients with the four
PE syndromes. SUBJECTS AND METHODS: Between January 2012 and January 2013, 438
consecutive heterosexual men complaining of PE and another 493 male healthy
subjects without the complaint were included in this study. Each of them
completed a detailed face-to-face questionnaire for information of demographics,
National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), and
International Index of Erectile Function-5 (IIEF-5). Each patient was classified
as one of the four PE subtypes: lifelong PE (LPE), acquired PE (APE), natural
variable PE (NVPE), or premature-like ejaculatory dysfunction (PLED). RESULTS:
There were no significant difference between patients and control subjects
regarding demographics. In the PE group, the prevalence of PLS were 32%, showing
statistical significance compared with control subjects (15.8%, P<0.001). And the
NIH-CPSI score was 10.0+/-7.9, showing significant difference compared with
control subjects (6.0+/- 5.4, P<0.001). Among the four PE syndromes, patients
with PLED had the highest prevalence of PLS (42.3%, P<0.001), but the difference
of NIH-CPSI scores among the four PE syndromes was not significant (P=0.055).
CONCLUSIONS: PLS were more common in patients with PE. Also, patients had worse
NIH-CPSI scores than the control subjects. Therefore, patients with PLED had the
highest incidence of PLS.
PMID- 25126188
TI - Risk factors target in patients with post-thyroidectomy bleeding.
AB - As the highly blood flow of thyroid gland post-thyroidectomy bleeding (PTB) is a
serious and life-threatening complication. Our aim was to investigate factors
that influenced bleeding after thyroidectomy. Between February 2008 and September
2012, the data of 4449 consecutive patients with thyroid diseases undergoing
thyroidectomy were collected and analysed from the department of surgical
oncology retrospectively. During the study period, 88 (2.0%) patients were
identified to have clinically PTB. 6 risk factors were significantly related to
PTB: gender (OR 3.243; 95% CI 2.078-5.061; P < 0.001), age (OR 1.025; 95% CI
1.006-1.043; P = 0.009), tumor size (OR 4.495; 95% CI 2.462-8.208; P < 0.001),
postoperative hypertension (OR 2.195; 95% CI 1.006-1.043; P = 0.035), lymph node
dissection (OR 3.384; 95% CI 2.146-5.339; P < 0.001) and Graves' disease (OR
3.744; 95% CI 1.920-7.303; P < 0.001). We addressed the most common explicit
source of bleeding by reexploration: infrahyoid muscles (30/88), beside the
laryngeal recurrent nerve (22/88), subcutaneous tissue (10/88) and superior pole
(10/88). In our study, male gender, older age, tumor size > 3 cm, postoperative
hypertension (SP > 150 mmHg), lymph node dissection and Graves' disease were
independent risk factors for PTB. The sources of bleeding were identified more
frequently in the infrahyoid muscles and beside the laryngeal recurrent nerve. It
is helpful for surgeons to decide the potential bleeding points during the
reexploration of PTB.
PMID- 25126189
TI - Gene profiling analysis for patients with oral verrucous carcinoma and oral
squamous cell carcinoma.
AB - Oral verrucous carcinoma (OVC) is one malignant tumor which was carved out from
the oral squamous cell carcinoma (OSCC). However, the clinical and pathological
features as well as the treatment strategies of OVC are different from OSCC.
Here, global transcript abundance of tumor tissues from five patients with
primary OVC and six patients with primary OSCC including their matched adjacently
normal oral mucosa were profiled using the Affymetrix HGU133 Plus 2.0. Ingenuity
Systems IPA software was used to analyse the gene function and biological
pathways. There were 109 differentially expressed genes (more than 2-fold)
between OVC and the adjacently normal tissue, among them 66 were up-regulated and
43 were down-regulated; 1172 differentially expressed genes (2-fold) between OSCC
and the adjacently normal tissue, among them 608 were up-regulated and 564 were
down-regulated. There were 39 common differentially expressed genes in OVC and
OSCC compared with their matched normal oral mucosa, among them 22 up-regulated
and 17 down-regulated, and 8 of them different between OVC and OSCC. In addition,
the gene expression profile was further validated by quantitative real-time PCR
(Q-RT-PCR) analysis for four of those 39 selected genes.
PMID- 25126190
TI - Effect of lower than expected number of oocyte on the IVF results after oocyte
pickup.
AB - OBJECTIVES: To investigate whether a lower than expected number of oocyte after
>=14 mm follicle aspiration during OPU has any effect on pregnancy outcomes
Methods: This is a retrospective study done between 2010 and 2013 at the IVF Unit
of the Zeynep Kamil Women and Children Diseases Education and Research Hospital,
dealing with the medical records of infertile patients who underwent IVF cycle
and controlled ovarian stimulation with long agonist or fix antogonist protocol.
The patients included into the study were those diagnosed with a primary
infertility, aged between 23 and 39, at a BMI of 22-28 kg/m(2) and having
received the first or second IVF treatment. Male factor, presence of uterine
anomaly, patients with serious endometriosis and patients with low ovarian
reserve were all excluded from the study. Typically, oocyte pick-up was performed
in all the patients 35.5 hours after the hCG implementation. Single or double
embryo transfer was performed, where available. Patients were classified into two
groups. Group 1 consisted of those with no difference between >=14 mm aspirated
follicle number and expected number of oocyte or with 1 missing number of oocyte
at the most. Group 2 consisted of those with at least >=2 missing number of
oocyte between aspirated follicle number and expected number of oocyte.
Statistical analysis was performed using Student's t test for continuous
variables and chi-square test for categorical variables. Additionally, a Linear
regression analysis was conducted between the total number of oocyte and
pregnancy. RESULTS: In total, 387 treatment cycles were included into the study.
Group 1 consisted of 134 patients and Group 2 consisted of 252 patients. Antral
follicle number (12.8 +/- 4.3 and 14.5 +/- 4.1, P = 0.0007), hCG day E2 value
(1990.7 +/- 1056.4 and 2515.2 +/- 1332.7, P < 0.0001) and the the number of
aspirated follicle during OPU (9.1 +/- 4.4 and 13.7 +/- 5.5, P < 0.0001) were
significantly higher in Group 2; whereas on the other hand, daily gonadotropin
dose (290.9 +/- 79.9 and 273.4 +/- 74.4, P = 0.034) and total gonadotropin doses
(2545 +/- 1031.8 and 2247.7 +/- 901.9, P = 0.004) were significantly higher in
Group 1. The pregnancy rate was significantly higher in Group 1 (29.1% and 19.4%,
P = 0.041). No correlation was observed between the number of oocyte and
pregnancy (r = 0.082, P = 0.107). CONCLUSIONS: The number of aspirated follicles
during IVF treatment being higher than the collected number of oocyte leads to a
statistically significant fall in the pregnancy rates. There is no correlation
between the number of oocyte and pregnancy.
PMID- 25126191
TI - Effect of male hepatitis B virus infection on outcomes of in vitro fertilization
and embryo transfer treatment: insights from couples undergoing oocyte donation.
AB - It is common to see HBV infected couple seeking fertility treatment in
reproductive medical centers. However, it is still unclear whether HBV infection
has any relationship with IVF outcome. To assess the impact of male HVB infection
on the outcomes of IVF, we retrospectively analyzed data from two hundred and
seventy-seven subfertile couples undergoing oocyte donation cycles in our center.
Twenty men (7.2%) were HBV seropositive in 277 couples. 20 couples with
seropositive husbands had similar semen parameters and fertilization rate when
compared with their controls. Among the 215 couples undergoing their first oocyte
donation cycles, 19 couples with seropositive husbands/seronegative wives had
lower implantation rate (26.7% vs. 40.6%; P > 0.05), and lower clinical pregnancy
rate (42.1% vs. 63.8%; P > 0.05), but the difference was not statistically
significant. In binary regression model, male HBV infection had no association
with clinical pregnancy. Our study shows that male HBV infection has little
impact on IVF outcomes.
PMID- 25126192
TI - Injection of MTX for the treatment of cesarean scar pregnancy: comparison between
different methods.
AB - The aim of this study was to analyze clinical treatment and outcome of injection
MTX for Cesarean scar pregnancy (CSP). We use retrospective study to compare the
time in CSP of blood chorionic gonadotropin (beta-HCG) and progesterone drooped
to the normal, blood flow resistance and hospitalization days. 34 patients
diagnosed with CSP were reviewed in our department from 2000 to 2013, including
clinical characteristics, early diagnosis, treatment methods and treatment
outcome. All patients were divided into B ultrasound-guided gestational MTX
inject group (Group one), local intramuscular treatment group (Group two) and
uterine artery perfusion MTX group (Group three). All cases had responded well to
treatment. Except three cases of local intramuscular serum beta-HCG decreased
slowly MTX 10 mg intramuscular again, the average serum beta-HCG decline of 65%
the 4th day after treatment. In intramuscular group, the average length of stay
is 19 +/- 2.1 days. Serum beta-HCG, progesterone recovery time were 20 to 89
days, an average of 54.5 days. B ultrasound-guided group hospital stay were 15 +/
3.1 days, serum beta-HCG, progesterone recovery time were 18 to 71 days, an
average of 44.5 days. In Uterine artery embolization group, the average length of
stay is 16 +/- 2.4 days, serum beta-HCG, progesterone recovery time were 20 to 70
days, an average of 45 days. Statistical data results using T-test and chi-square
test analysis. Three groups of beta-HCG, progesterone decreased to normal days
the difference was statistically significant (P < 0.05), but uterine artery
embolization group and ultrasound-guided group B showed no significant difference
(P > 0.05). B ultrasound-guided gestational injection of MTX and uterine artery
embolization perfusion MTX are the better ways to treat uterine scar pregnancy.
PMID- 25126193
TI - Combined effects of astragalus soup and persistent Taiji boxing on improving the
immunity of elderly women.
AB - OBJECTIVE: To observe the combined effects of astragalus soup and persistent
Taiji boxing on improving the immunity of women of advanced years. DESIGN: 120
elderly women lacking daily exercise were chosen as the study subjects. By using
the table of random numbers, they were then divided into the control group and
the experiment group, consisting of 60 each. The control group practiced Taiji
boxing for 45 minutes twice a day. The experiment group did the same, and, in
addition, took astragalus soup after each boxing. Indexes related to physical
immunity of the two groups were observed and compared when they were first
chosen, when the alternative treatment was applied three, six and twelve months
later, respectively. RESULTS: The two groups demonstrated no significant
differences in general data and research indexes when chosen (P > 0.05). Three
months after the two groups were chosen and treated differently, the control
group demonstrated no significant improvement while most indexes of the
experiment group improved considerably (P > 0.05). After six months, the related
indexes of both groups improved substantially (P < 0.05) and the improvement with
the experiment was even clearer (P < 0.05). Twelve months later, the improvement
with the experiment group was more noticeable (P < 0.01 or P < 0.05).
CONCLUSIONS: In a relatively short period of three months, Taiji boxing produces
no noticeable effect on the improvement of immunity in elderly women. However,
when they resume the exercise for another three months and longer, Taiji boxing
has a noticeable advantage and the effect is the most favorable when it is
combined with astragalus soup.
PMID- 25126194
TI - Pentacam could be a useful tool for evaluating and qualifying the anterior
chamber morphology.
AB - OBJECTIVE: This study aims to investigate the changes of anterior chamber
morphology after laser peripheral iridotomy (LPI) in primary angle-closure (PAC)
patients using Pentacam. METHODS: 35 normal persons and 35 patients of PAC before
and 1 week after neodymium: yttrium: aluminum garnet (Nd: YAG) LPI were evaluated
with Pentacam. We measured the anterior chamber angle (ACA), central anterior
chamber depth (CACD), peripheral anterior chamber depth (PACD), anterior chamber
volume (ACV) and pupil diameter (PD). Paired t-test was used to investigate the
differences in anterior segment parameters before and after LPI. Independent
samples t-test was used to compare these parameters between PAC patients after
LPI and normal persons. RESULTS: There were significant differences between PAC
patients and control in nasal and temporal ACA, PACD, ACV (P < 0.05) except for
superior (P = 0.053) and inferior ACA (P = 0.389), CACD (P = 0.453) and PD (P =
0.221). ACV increased 56.5% in PAC patients after LPI whose ACV < 57 mm(3), which
was more greatly than those patients whose ACV > 57 mm(3) (P = 0.001).
CONCLUSIONS: The changes of anterior chamber parameters after LPI in PAC eyes can
be demonstrated by Pentacam objectively and quantitatively. LPI seems more
effective for PAC eyes with smaller ACV. The anterior chamber parameters in PAC
eyes after LPI are still significantly smaller than those of normal persons.
PMID- 25126195
TI - Respiratory symptoms and pulmonary function tests in security and safety products
plant workers.
AB - OBJECTIVE: Lock and key factory workers are under the risk of metal
pneumoconiosis and occupational asthma. In this cross-sectional study, it's aimed
to evaluate the relationship between metal dust exposure and respiratory
symptoms, pulmonary function tests of workers in different section of lock and
key factory. METHODS: 54 male workers (mean age, 32.8 +/- 5.4) in a security and
safety products plant were evaluated for respiratory symptoms, pulmonary function
tests and smoking habits. Results have been interpreted by comparison of the
painting (28/54) and grinding group workers (26/54). RESULTS: There was no
significant difference between painting (32.1 +/- 4.8) and grinding (33.6 +/-
6.1) groups regarding mean age (P > 0.05). Smokers were in significantly higher
in grinding group (18/26). Cough and sputum were reported 14.3% (4/28) in
painting and 3.8% (1/26) in grinding workers (P > 0.05). Chest tightness was seen
in 7.1% and 7.7% of painting and grinding workers, respectively (P > 0.05). But
no chest tightness was reported in both groups when they were away work.
Breathlessness was seen in 10.7% and 7.7% of painting and grinding workers,
respectively (P > 0.05). Breathlessness was similar in both groups (7.1% vs.
3.8%) when they were away work. When comparing painting and grinding workers
respiratory functions no significant difference observed. Chest radiography in
painting and grinding workers showed hyperlucency (3.6% vs.11.4%), respectively.
CONCLUSION: Painting groups in lock and key factory workers had more but
statistically insignificantrespiratory complaints. Interestingly, chest tightness
was only observed when both groups were at work. It was thought that ventilation
and using personal protective equipment in factory could provide significant
benefits.
PMID- 25126196
TI - Clinical efficacy of Xinkeshu Pian on coronary heart disease and mood disorder
complications after PCI.
AB - AIM: To assess the efficacy and safety of combining Xinkeshu tablet treatment
with routine Western medicine treatment for patients with coronary heart disease
(CHD) and mood disorders after PCI postoperative period. METHOD: 100 patients
were randomly divided into treatment group of 50 cases, and control group of 50
cases. The control group was given routine Western medical treatment, whereas the
treatment group was given routine Western medical treatment in combination with
Xinkeshu tablets. Eight weeks after treatment, the patients underwent SF-36 life
quality evaluation, self-rating depression scale (SDS) evaluation, and self
rating anxiety scale (SAS) evaluation. RESULT: After the eight-week treatment,
the SF-36 life quality scores, SAS scores, SDS score, as well as the reduction in
heart creatinine levels of the two groups were compared. The results show
statistical significance (P<0.05). CONCLUSION: Xinkeshu can effectively address
the PCI postoperative mood disorders in patients with coronary heart disease and
improve the quality of life.
PMID- 25126197
TI - Pulmonary epithelioid hemangioendothelioma coexisting with pulmonary nodular
amyloidosis: case discussion and review of the literature.
AB - A 38-year-old female was found to have multiple bilateral lung nodules in a
routine chest X-ray examination. Thoracoscopy was performed with biopsy of three
nodules from the right lower lobe and Congo red staining showed typical amyloid
pattern. Initial diagnosis of pulmonary nodular amyloidosis was made. However,
one nodule in the right upper lobe enlarged as detected by follow-up CT scan. The
patient underwent F-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG
PET)/CT and a significant high FDG uptake in the largest nodule in right upper
lobe was observed while the uptake was normal or mildly increased in the other
nodules. Meanwhile, right hilar and mediastinal lymph nodes adenopathy was noted.
Right upper lobe was resected by thoracotomy. Surprisingly, histopathological
findings showed pulmonary epithelioid hemangioendothelioma (PEH) with metastasis
of hilar and mediastinal lymph nodes. To our knowledge, this is the first
described case of PEH coexisting with pulmonary nodular amyloidosis.
PMID- 25126198
TI - Primary mediastinal adenocarcinoma originating from a calcified nodule.
AB - Primary mediastinal adenocarcinoma is rare, but its originating from a calcified
nodule is even more unusual. We present herein a 55-year-old female with a
superior mediastinal mass, first discovered 2 years prior that changed
dramatically from its original appearance as a calcified nodule. The mass was
completely resected, and histopathological examination revealed a primary
adenocarcinoma. The patient has been disease-free for over 13 months since
surgery. To the best of our knowledge, this is the first reported case of
mediastinal adenocarcinoma to demonstrate such a surprising course of
development.
PMID- 25126200
TI - Use of improved tracheal catheters in patient of tracheostomy tube-induced
tracheoesophageal fistula: a case report.
AB - Tracheostomy tube might cause tracheoesophageal fistula (TEF) due to high cuff
pressure or direct mechanical trauma. Surgical repair provides the ideal way to
deal with TEF but it necessitates the weaning the patient from mechanical
ventilation. Here we report a spontaneous closure of TEF by managing it with
improved tracheal catheters in a patient who is dependent on mechanical
ventilation.
PMID- 25126199
TI - Successful treatment of polymorphic post-transplant lymphoproliferative disorder
after allo-HSCT with reduction of immunosuppression.
AB - Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening
complication for recipients of solid organ transplantation (SOT) and allogeneic
hematopoietic stem cell transplantation (allo-HSCT). In SOT recipients, who
previously have a normal immune system that has been immunosuppressed, reduction
of immunosuppression (RI) shows favorable outcome. However, in HSCT recipients,
who have been profoundly immunosuppressed and for whom the tempo of immune
reconstitution cannot be fast enough to eliminate the lymphoproliferative
process, RI is ineffective in most patients. Therefore, cases of tumor regression
via RI alone are rare in the setting of HSCT. We present a case of 26-year-old
female developing a polymorphic B-cell PTLD 4 months after receiving allo-HSCT
for T cell lymphoblastic lymphoma. RI alone led to regression of the
nasopharyngeal tumor, and no sign or evidence of graft-versus-host disease (GVHD)
after RI was observed. The general condition of this patient was quite well just
before we submitted our draft. To our knowledge, this is the first case that
tumor of PTLD regressed upon RI alone with a favorable prognosis and without any
evidence of GVHD and relapse of PTLD after RI therapy in the setting of HSCT,
which justify the possible advantage of RI alone for low-risk patients.
PMID- 25126201
TI - Diagnostic and prognostic roles of DOG1 and Ki-67, in GIST patients with
localized or advanced/metastatic disease.
AB - AIM: Gastrointestinal stromal tumor is the most common mesenchymal neoplasia in
the gastrointestinal tract and has a broad spectrum of pathological patterns and
also clinical features changing from benign to malignant. Although the well
characterized parameters to predict the outcome have been the size and the
mitotic index of the tumor in the patients with early-staged disease, bulky
recurrent or metastatic tumor, resistance to medical treatment and mutation
analysis are the prognostic factors for advanced stage-GIST. The aim of this
study is to investigate new and more practical tissue markers, such as DOG1 and
Ki-67 to specify the GIST diagnosis and also to predict the outcome in GIST
patients with both localized and advanced staged disease. METHODS: For the last
14 years, from 1999 to 2013, 111 patients with a histopathological GIST diagnosis
from the hospital files were enrolled to the study. In their parafin-embedded
tissue samples, DOG1 and Ki-67 expressions were evaluated with
immunohistochemisty by two independent pathologists from Cukurova University
Medical Faculty. Patients were divided into two groups, the patients with
localized disease treated by surgery and the patients with advanced/metastatic
disease. DOG1 and Ki-67 expressions were corelated with other diagnostic and
prognostic histopathological markers and also the clinical outcome in these two
group of patients. RESULTS: The specificity and the sensitivity of DOG1 in GIST
diagnosis was found 94 and 43%, respectively. DOG1 expression was especially
important in the diagnosis of c-kit negative cases. Although Ki-67 was not found
a statistically significant prognostic factor for overall survival, it was
strongly corelated with mitotic index which is a well-known standart prognostic
factor for localized disease. DISCUSSION: DOG1 seems to be an important
diagnostic tool for clinically suspected GIST diagnosis in both advanced or early
staged patients whose tumours are c-kit expression negative. On the other hand,
Ki-67 can be a stronger candidate for prognostic factor instead of mitotic index
to identify the proliferative cells out of mitotic phase but this statement needs
be prospectively validated on studies with large number of patients.
PMID- 25126202
TI - Vitamin A supplementation alleviates extrahepatic cholestasis liver injury
through Nrf2 activation.
AB - AIM: To investigate the role of vitamin A in liver damage induced by bile duct
ligation (BDL) in rats. METHODS: Thirty male Wistar rats were randomly divided
into three groups: SHAM group, BDL group, and BDL + VitA group . The
concentrations of retinol and retinyl palmitate in the liver were analyzed using
HPLC, and liver function was evaluated by the level of TBIL, ALT, AST, and ALP in
serum. Hepatic oxidative status was estimated by measuring T-SOD, CAT, GSH, MDA,
and AOPP. Nrf2 expression was assessed using immunohistochemistry and western
blotting, and EMSA was performed to determine Nrf2 DNA-binding activity. The
expression of the downstream factors such as Ho1 and Nqo1 was also examined using
immunohistochemistry and western blotting assays. RESULTS: Vitamin A treatment
restored levels of retinoids in liver, improved liver function, alleviated
oxidative stress, and facilitated the translocation of Nrf2 to the nucleus in the
experimental obstructive jaundice. Vitamin A was also found to increase the
expression of Nrf2 downstream proteins such as Ho1 and Nqo1. CONCLUSION: Vitamin
A was here found to ameliorate cholestatic liver injury. This effect may be
related to the activation of Nrf2/ARE pathway in bile duct ligation rats.
PMID- 25126204
TI - What kind of healthcare debate do we want?
PMID- 25126205
TI - Welcome to our community.
PMID- 25126206
TI - Creating a 21st-century intelligent health system.
AB - In most areas of life, Americans enjoy the ease and convenience offered by
advances in technology, communications, and transportation. Every day we
experience the 21st-century model of America, which is one of effectiveness,
accuracy, speed, flexibility, efficiency, lower cost, more choices, and greater
achievement. We can shop online, compare prices for goods and services, and when
decisions need to be made, we have access to a wide array of information sources
to assist in making those decisions. In short, Americans enjoy great latitude in
our power to determine what is best for us. This is not, however, the case when
it comes to health and healthcare. In our current healthcare system, individuals
are dependent on a structure that has resisted the natural progress and
modernization achieved by market-oriented, 21st-century industries. The
information age has been leaving health behind. Although it is the nature of a
science- and technology-based entrepreneurial free market to provide more choices
of higher quality at lower cost, in the healthcare sector, prices continue to
rise, quality is inconsistent, and individuals lack the information, incentives,
and power to make choices.
PMID- 25126207
TI - Medicare Coverage Strategies: Impact of the MMA and PBMs.
AB - American Health & Drug Benefits TM has been created to act as an ideological
melting pot focusing on health and drug benefit decision makers, as well as those
who may affect or may be affected by those decisions. By engaging in
conversations with payors, regulators, employers, and other stakeholders, our
journal hopes to enable decision makers to view the impact of benefit designs
from as many perspectives as possible. Through this open dialogue, we hope that
better decisions may be made, and that the greater healthcare marketplace will be
positively impacted. In following our editorial mission, American Health & Drug
Benefits TM has sought thought leaders who have influenced and will continue to
influence the healthcare marketplace. During a fall visit to Washington, DC, Dr.
Joseph Antos was kind enough to host a visit to the American Enterprise Institute
and provide his thoughts to Robert Henry, editor-in-chief, on how the Centers for
Medicare & Medicaid Services (CMS) exerts its influence on drug coverage in the
wake of the Medicare Modernization Act (MMA) and in the face of evidence-based
medicine standards. Following a chronology of CMS's role from its inception to
current events, Dr. Antos offers a lively insight into CMS's strategy and its
tactical effects on the American healthcare system.
PMID- 25126208
TI - Role of NCCN in Integrating Cancer Clinical Practice Guidelines into the
Healthcare Debate.
AB - Many new drugs and drugs in the pipeline are referred to as targeted therapy.
Targeted therapies have revolutionized the care of certain cancers, such as
chronic myelogenous leukemia, but for other common malignancies, such as colon
cancer, the impact on survival has been more modest. These seemingly incremental
improvements coupled with the high cost of targeted therapy have focused the
debate about the cost of healthcare squarely on oncology. Clinical practice
guidelines are a common baseline starting point for this debate. Guidelines
reflect clinical evidence and expert judgment, which is necessary to fill in the
gaps when clinical evidence is not yet available or is evolving quickly. In
addition, clinical guidelines inform other key aspects of oncology care, such as
establishing a standard of care, which can then be translated into quality
measures. Guidelines can also be reformatted to create an oncology drug
compendium or rewritten to provide patient information.
PMID- 25126209
TI - Measuring the value of treatment to patients: patient-reported outcomes in drug
development.
AB - Patient-reported outcomes (PROs) can be important measures of the impact and
value of new drug treatments to patients. Recently, both multisector stakeholder
groups and the U.S. Food and Drug Administration have carefully considered and
issued guidance on best practices for the use of PROs in measuring treatment
impact. When best practices are followed and PRO data are appropriately included
in drug development strategy and clinical trials, these data can be part of the
evidence submitted for drug approval and included in drug labeling. One study
showed that PRO data were included in 30% of a sample of new drug labels and were
more concentrated in certain therapeutic areas, such as anti-inflammatory agents,
vaccines, gastrointestinal agents, and respiratory and urologic agents. PRO data
included in labeling, or generated in a similar scientific manner, may often then
be used in other communication vehicles, such as formulary submission dossiers,
journal or direct-to-consumer advertisements, publications, or continuing medical
education. Meaningful and reliable PRO results regarding the effects of new
treatments on how patients feel and function provide useful information to those
who must make decisions about the availability and utilization of such
treatments.
PMID- 25126210
TI - Approvable letters in 2007 and the outlook for 2008.
PMID- 25126203
TI - The beneficial effect of melatonin in brain endothelial cells against oxygen
glucose deprivation followed by reperfusion-induced injury.
AB - Melatonin has a cellular protective effect in cerebrovascular and
neurodegenerative diseases. Protection of brain endothelial cells against hypoxia
and oxidative stress is important for treatment of central nervous system (CNS)
diseases, since brain endothelial cells constitute the blood brain barrier (BBB).
In the present study, we investigated the protective effect of melatonin against
oxygen-glucose deprivation, followed by reperfusion- (OGD/R-) induced injury, in
bEnd.3 cells. The effect of melatonin was examined by western blot analysis, cell
viability assays, measurement of intracellular reactive oxygen species (ROS), and
immunocytochemistry (ICC). Our results showed that treatment with melatonin
prevents cell death and degradation of tight junction protein in the setting of
OGD/R-induced injury. In response to OGD/R injury of bEnd.3 cells, melatonin
activates Akt, which promotes cell survival, and attenuates phosphorylation of
JNK, which triggers apoptosis. Thus, melatonin protects bEnd.3 cells against
OGD/R-induced injury.
PMID- 25126211
TI - The 2007 Pharmaceutical and Biotech Pipeline Year-End Summary: What it Says About
the State of the Art of Discovery & Development.
PMID- 25126212
TI - Risk factors, subjectivity, and truth in healthcare.
PMID- 25126213
TI - Patent reform proposals raise the stakes for researchers, manufacturers of
biologics.
AB - When the founding fathers provided for patents in the American Constitution, they
could hardly have envisioned the 21st-century demands the U.S. Patents and
Trademarks Office (PTO) face today. The PTO is an institution that is, by
definition, concerned with the new-one essential element of a patent is novelty;
however, it is also struggling to fit the needs of modern biotech research and
development within a framework conceived by the young American government in the
18th century. In their new book Biotechnology and the Patent System (AEI Press,
Washington, DC, 2007), Claude Barfield, PhD, and John Calfee, PhD, both Resident
Scholars at the American Enterprise Institute, Washington, DC, discuss reforms
being considered by legislators, lawyers, and members of the biotechnology
industry that could modernize the patent system and make it work for all the
stakeholders. The proposed reforms include changing the way patent applications
are filed and pursued, limiting encumbrances that slow the application process,
providing more funding to the PTO to speed consideration of applications,
granting interested parties the right to intervene while a patent application is
being considered, and limiting the administrative and economic burdens associated
with the mushrooming numbers of patents for each product or process.
PMID- 25126214
TI - The value of biologics.
AB - American Health & Drug BenefitsTM has reached out to a health and drug benefit
decision maker to open a dialogue on the benefits coverage implications
surrounding the high cost of biologic drugs. We asked Dr. Gary Owens to discuss
with us how payors are turning data points, demographic trends, and pharmacologic
discoveries into formularies and benefit designs that balance the demands of
cost, quality, and access to care. With a decade of experience chairing the
Pharmacy & Therapeutics Committee at Independence Blue Cross until 2006 to inform
him, Dr. Owens described how benefit design structures are being redesigned to
meet these interlocking needs.
PMID- 25126215
TI - When novelty is not enough.
AB - Neither orderly nor fully rational, the current healthcare environment is a
mosaic of providers, products, services, and intermediaries delivering
healthcare, regulatory, and other government institutions, and consumers. The
information required for informed healthcare decisions for novel pharmaceutical
interventions varies appreciably with the audience, the therapeutic area, and the
stage of product development. In this environment, the viability of new product
introductions can be heavily influenced by perceived value as well as by
mechanistic novelty. Correspondingly, research and development activities can be
influenced profoundly by the use of incentive-based formularies, prior
authorization requirements, or systems of reimbursement that mandate a stream of
evidence confirming clinical utility in the presence of therapeutic uncertainty
(eg, Centers for Medicare & Medicaid Services, Coverage with Evidence
Development). The economic impact of innovative technology on the healthcare
system, as well as the effects on the individual patient, can become a
significant variable that influences the extent of research activities from the
bench to the physician-patient-payor interface.
PMID- 25126216
TI - Asthma-The National Surveillance Data and the National Asthma Education and
Prevention Program's Expert Panel Report 3.
AB - "The disease often begins in childhood and sometimes lasts until old age. It may
follow an attack of whooping cough. One of the most striking peculiarities is the
bizarre and extraordinary variety of circumstances, which at times induce a
paroxysm. Among these local conditions, climate or atmosphere is most important."
-William Osler, MD (1905) Asthma was familiar to various Greek and Roman authors;
however, the attacks of severe wheezing were confused with dyspnea from other
causes.1 By the 1900s many of the key attributes of the disease state were well
described, such as spasm of the bronchial muscles, swelling of the bronchial
mucous membrane, and the role of inflammation. The disease was recognized to run
in families, and to be influenced by provocative stimuli such as odors, flowers,
hay, and emanations from animals.2 Today, asthma continues to be recognized as a
chronic inflammatory disease of the lungs, which typically presents with
intermittent cough, wheezing, shortness of breath or dyspnea, and chest
tightness, commonly occurring during the night and early morning. The underlying
inflammation leads to airway hyperresponsiveness and obstruction with some degree
of reversibility. This inflammatory reaction may result in sudden exacerbations
and chronic progressive structural changes within the lung.
PMID- 25126218
TI - The great p value: we the people.
PMID- 25126217
TI - Behind-the-Counter Drug Access.
PMID- 25126219
TI - Health reform in america.
PMID- 25126220
TI - Medicare coverage policies for biologics: the broad gray line.
AB - In October 2007, American Health & Drug Benefits asked Dr Joseph Antos to discuss
the forces that have shaped Medicare's policies and their impact on the various
stakeholders in US healthcare. The first part of the interview appeared in AHDB
in February 2008. This second part focuses on the impact of the Centers for
Medicare & Medicaid Services drug coverage on the future of biologic products.
This discussion does not reflect any new developments occurring after October,
such as the recent recommendation of the US Food and Drug Administration advisory
committee to narrow the indication for erythropoiesis-stimulating agents to
patients with cancer.
PMID- 25126221
TI - Benchmarking new frontiers in managed care pharmacy.
AB - In 2006, the Foundation for Managed Care Pharmacy-a nonprofit charitable trust
affiliated with the Academy of Managed Care Pharmacy-sponsored a survey that was
conducted by The HSM Group, a national healthcare market research and consulting
firm, and supported by an unrestricted grant from Merck & Co. The survey was
repeated in 2007 and was designed to track the evolution of new healthcare
trends, gauge the role of managed care pharmacy experts in these trends and the
initiatives evolving from them, and disseminate that information to the various
stakeholders of the industry. The authors examine the responses of 186
respondents from 71 national health plans, 54 pharmacy benefit management
companies, as well as several hospitals, health systems, physician groups, or
pharmacies. Survey findings highlight emerging trends in healthcare today and
provide insight into the role of managed care pharmacy experts in today's
healthcare environment, as well as other variables that may affect the future of
the US healthcare delivery system.
PMID- 25126222
TI - Not Waiting for Godot: The Evolution of Health Promotion at PPG Industries.
AB - PPG Industries is a manufacturer of coatings, chemicals, optical products,
specialty materials, glass, and fiberglass. The company's approach to healthcare
combines perhaps 2 disparate concepts. The first is that employee health and
behavior change relies to a large degree on employee awareness and ownership of
their own health and second that "what gets measured gets done." It is widely
acknowledged that one of the best tools for employee awareness is the health risk
appraisal tool. Additional components of employee awareness include knowing key
individual health metrics and effectively engaging with healthcare providers. As
a leading global manufacturer, PPG well understands the critical importance of
cost accounting and financial metrics to drive business decisions. PPG's perhaps
unique approach comes from the strong marriage of individual health/wellness
promotion and frequent, timely, and informative financial metrics on health and
the cost of care. Combining capacity building through the mobilization of
volunteer wellness teams with expert interventions and financial discipline is a
feature of the experience here described. This approach has resulted in both
management and employee engagement in the issue and has allowed PPG to bend the
curve of ever-increasing healthcare costs and achieve cost increases per employee
at one half the reported national average for companies of comparable size.
Because this journal is dedicated to health and drug benefits, we gathered an
appropriately representative team composed of a physician, an epidemiologist who
resides in a pharmacy school, and a benefits manager. The team evolved from a
common vision to identify ways of improving employee health and well-being. The
team presented both as keynote speakers and as contributors to a breakout session
at the National Symposium on Work-Life organized in 2007 by the National
Institute for Occupational Safety and Health, a federal agency of the Centers for
Disease Control and Prevention in the Department of Health and Human Services.
This article is an account of why and how such a unique team was formed.
PMID- 25126223
TI - Meta-analysis 101: what you want to know in the era of comparative effectiveness.
AB - In the era of "comparative effectiveness" research, each of the major
stakeholders in healthcare-payors, patients, providers, and government-face a
similar challenge. When making a decision about whether a new device, drug, or a
diagnostic modality should be considered for use or coverage, what choices are
best supported by the evidence? Medical evidence is defined by randomized
controlled trials and by observational studies that vary greatly in their design,
the accuracy of their analyses, and the relevance of their conclusions and
recommendations. Hence, key decision makers increasingly rely on systematic
reviews and meta-analyses to facilitate the interpretation and application of
research evidence. Knowing how to evaluate meta-analyses and understanding the
potential pitfalls of the method are crucial for those involved in designing drug
benefits. The authors highlight the process, strengths, and weaknesses of meta
analysis and explain how to judge the value of the results.
PMID- 25126224
TI - Depression overview.
AB - Depression is a common condition that often remains undiagnosed and untreated;
however, symptoms are more likely to be recognized today than in past decades.
Survey data suggest that female, nonwhite patients are more likely to report
depressive symptoms, especially those who are less educated, poor, and covered by
Medicaid. Depression may be a finding suggestive of dysthymic disorder, minor or
major depressive disorder, seasonal affective disorder, episodic depression, or a
sign of an associated mood disorder, such as bipolar disorder. Many effective
treatments are available that are well tolerated. This article outlines the
diagnostic approach used in primary care, as well as the different treatment
options available for this condition. Depression can have serious consequences
and must be treated appropriately.
PMID- 25126225
TI - Seizing the opportunity.
PMID- 25126227
TI - Avoiding the unthinkable: a tale of 2 triangles and the process of care they
govern.
PMID- 25126226
TI - Regulatory concerns fuel hunger in congress for FDA reform.
PMID- 25126228
TI - The unbearable lightness of mental health.
PMID- 25126230
TI - Managed care and medicare use of generics: seizing the opportunity, part 2.
PMID- 25126229
TI - Schizophrenia: current concepts and approaches to patient care.
AB - Schizophrenia is the most serious of all mental conditions. It is typically a
long-lasting condition characterized by repeated relapses and by marked
functional impairment. Genetic and environmental factors are important. Exactly
which factors and how these combine to cause schizophrenia is still unclear.
Antipsychotic medications form the bedrock for treatment. These drugs are
effective, but not entirely so, and are associated with negative side effects.
Individual differences among the available medications suggest that trials with a
different medication may be appropriate when one agent fails or is not
appropriate for the specific patient. Monitoring for side effects is important to
ensure efficacy and compliance. Often, patients choose to stop taking their
medications for a variety of reasons, which invariably will lead most patients to
a relapse of illness. Beyond medications, patients need considerable support and
specialized services. Families are a key resource. The recent focus on personal
determination has led to recovery-based services, including the incorporation of
peer support into patient care.
PMID- 25126231
TI - Trends in pharmaceutical expenditures: the impact on drug benefit design.
AB - Annual national spending for pharmaceutical agents was increasing at a rapid pace
during the late 1990s and early part of the 21st century, outpacing increases in
spending on hospital care and on physician services, which had dominated the
industry in the 1970s. In the past few years, however, this trend has shifted,
resulting in a lower growth rate in 2005. The reasons for these trends of
increases and subsequent declines are explained in this article, including the
slower pace of increase in generics and the increasing role of biologic agents in
the rate of pharmaceutical price inflation. The sharp increases in drug spending
led to changes in prescription drug benefit designs that have not been fully
tested. The recent decline creates an opportunity for health plans to evaluate
the value of current and new strategies and implement value-based benefit designs
in accordance with the shifting focus in healthcare toward value-based patient
care.
PMID- 25126233
TI - What is happening to the pipeline?
PMID- 25126232
TI - Medicare coverage for erythropoiesis-stimulating agents: the perfect storm.
AB - Medicare policy changes have an immediate impact on health plans with regard to
setting payment policy for providers. So when Medicare tightened payment
guidelines for a lucrative class of anemia drugs-erythropoiesis-stimulating
agents-an ambitious set of rules was put into effect. Health plans often follow
suit in short order, enforcing public guidelines on private payors, even when
saving money is not a consideration. However, when Medicare takes an unreasonably
hard line, plans tend to focus on members and physicians more fervently,
attempting to soften the hard line. In this first part of the interview, Dr
Silver examines the coverage decisions set by the Centers for Medicare & Medicaid
Services for the use of erythropoiesis-stimulating agents and discusses the
issues surrounding their adoption, indications versus off-label use, as well as
lingering questions about their role in tumor progression and other risk factors.
PMID- 25126234
TI - Results-driven Healthcare: Addressing the Staggering Cost of Poor Performance.
PMID- 25126235
TI - Comparing pharmacy benefit managers: moving well beyond the simple spreadsheet
analysis.
AB - Unabated increases in prescription drug demands, advancing technology, and rising
drug inflation rates combined with a sagging economy, continue to intensify
budget pressures for payors responsible for delivering pharmacy benefits to plan
members. At the same time, high levels of complexity and resource requirements in
drug benefit administration have led to a state in which plan sponsors remain
heavily dependent on pharmacy benefit managers to assist in these efforts. With
pharmacy representing such a critical component of healthcare delivery from
clinical and economic perspectives, it is essential that sponsors exercise high
levels of due diligence in pharmacy benefit manager review and appraisal to
ensure proper balance of quality clinical care, sufficient access, and optimal
cost-efficiency in the delivery of such benefits. This review is designed to
provide a comprehensive understanding of current pharmacy benefit management
business practices and help equip plan sponsors with the knowledge, strategies,
and safeguards to drive a well-informed pharmacy benefit selection process and,
inevitably, a better-aligned pharmacy benefit management-payor relationship.
PMID- 25126236
TI - Where generics and biologics meet.
PMID- 25126237
TI - Capnography monitoring enhances safety of postoperative patient-controlled
analgesia.
AB - BACKGROUND: Patient-controlled analgesia is associated with potentially fatal
opioid-related respiratory depression. Opioids are a well-recognized cause of
respiratory depression. However, in the postoperative patient, unrecognized
pulmonary disease may lead to retention of carbon dioxide, which is further
antagonized by opioids and may lead to life-threatening respiratory depression.
Therefore, using a method that would provide earlier warnings for respiratory
problems could improve patient outcomes. OBJECTIVE: To assess the efficacy of
monitoring postoperative patients who were receiving patient-controlled opioid
therapy with capnography modules in addition to the routine use of pulse oximetry
to monitor ventilatory status and generate alerts when respiratory parameters
exceed hospital-established limits. METHOD: Postoperative patients receiving
patient-controlled analgesia were compared in relation to the use of pulse
oximetry and capnography modules and their ability to generate alerts about
abnormal respiratory parameters. A total of 634 patients receiving patient
controlled analgesia therapy were studied, of whom 239 (38%) received
hydromorphone, 297 (47%) received morphine, and 98 (15%) received fentanyl. All 9
patients experiencing respiratory depression received supplemental oxygen.
RESULTS: Of the 634 patients studied, 9 (1.4%) experienced respiratory depression
by bradypnea (<6 breaths per minute). Six (67%) events were related to
hydromorphone and 3 (33%) were related to morphine. In 7 (78%) events, there was
no basal infusion rate and the saturation of peripheral oxygen was >92%. All
respiratory depression events occurred within the first 24 hours of patient
controlled analgesia therapy. In all cases, capnography, but not pulse oximetry,
alerted the nurse to impending respiratory depression. CONCLUSIONS: Capnography
was more effective than pulse oximetry in providing early warning of respiratory
depression in patients receiving supplemental oxygen. Capnographic monitoring and
automatic pausing of patient-controlled analgesia improved postoperative outcomes
in situations that could have otherwise been fatal. Use of capnography improved
clinician confidence that opioid dosing could be safely continued in
postoperative patients for more effective pain management.
PMID- 25126238
TI - The NCCN Compendium for Cancer Management.
AB - Early in 2008, American Health & Drug Benefits asked Dr Bill McGivney to discuss
the National Comprehensive Cancer Network Drugs and Biologics Compendium and
guidelines, which represent the evaluation of current evidence on cancer
management and the integration of expert judgment in a consensus fashion by
oncologists from National Comprehensive Cancer Network institutions. Several
advantages that may explain the increasing popularity and acceptance of the
Compendium and the guidelines are the authoritative nature of the National
Comprehensive Cancer Network experts, the rapid updates, and the free online
access. The Centers for Medicare & Medicaid Services reference the guidelines
specifically on coverage questions related to oncology and is currently
evaluating whether to recognize the Compendium as a basis for Medicare coverage
decisions for cancer patients. A decision is expected in June 2008. In January
2008, UnitedHealthcare announced that it would be using the Compendium as a basis
for their coverage decisions for patients with cancer, a fact that may influence
other private health insurance companies to follow suit. In this interview, Dr
McGivney discusses some of the unique features of the guidelines and the
Compendium and what differentiates them from available guidelines and compendia
of other cancer organizations, including the American Society of Clinical
Oncology.
PMID- 25126239
TI - Contracting for compliance: using adherence as a patient-centered measure of
performance.
PMID- 25126241
TI - FDA bolsters its generic approval process: health plans reap the benefits.
PMID- 25126240
TI - Wayward prescriptions: costs of fraud in payor plans.
AB - The cost of prescription drugs and medical devices has increased dramatically
over the past several years. This increase has exceeded the annual average
inflation index, making medical products desired sources of ill-gotten financial
gains through diversion, theft, fraud, and deceit. With databases often being
compromised, personal health information, personal identification, and therapy
history are all available to be used by thieves through deception and
misrepresentation, and are being traded on clandestine websites. With increasing
values of medical services, wanted efforts continue to emerge in profiteering
schemes, using illicit deals for financial gains by exploiting what was once
perceived as sacred areas of medical care. Estimates of healthcare resource costs
in dollars, lives, and products exceed $200 billion. Select examples of fraud in
our medical services are presented that expose plan members to the risks of loss
and theft that can compromise the privacy of their health records. The author
outlines prevention steps for payors to guard against such practices.
PMID- 25126242
TI - Heparin at the center of the storm.
PMID- 25126243
TI - Prescribing warfarin appropriately to meet patient safety goals.
AB - The anticoagulant warfarin is increasingly used in a variety of disorders
associated with risk of thromboembolism. The drug is undoubtedly effective but is
linked to numerous nutrient, disease, and drug interactions; safe use of warfarin
therefore necessitates close patient monitoring, using the international
normalized ratio. The predominant adverse effect is bleeding, and individuals
respond to warfarin in different ways. Both high and subtherapeutic international
normalized ratios warrant attention, whereas a high international normalized
ratio, with or without bleeding, mandates prompt patient evaluation. The 2008
National Patient Safety Goals require medical institutions to develop processes
to ensure the safe use and monitoring of anticoagulant use. Last August, the US
Food and Drug Administration revised the prescribing information for warfarin to
include genetic testing before initiating therapy, although this is still not
covered by most health plans.
PMID- 25126245
TI - The international society for pharmacoeconomics and outcomes research:
implications for decision makers in healthcare.
PMID- 25126244
TI - Treading water: the no-growth investment in health services research.
AB - There is a "perfect storm" brewing in the American healthcare system. Healthcare
spending has grown faster than our economy for many years and is projected to
double in as little as 10 years. In spite of what we spend on healthcare,
research tells us that we only receive appropriate care half the time. We are
simply not getting what we are paying for. Health services research provides the
data and the evidence needed to make better decisions, design healthcare
benefits, and develop effective policies to optimize healthcare financing,
facilitate access to healthcare services, and improve healthcare outcomes.
Despite what we know and what we can learn from health services research, federal
funding for this important field continues to erode. This article provides a
primer on the federal budget process and summarizes findings from the Federal
Funding for Health Services Research 2007.
PMID- 25126246
TI - Quality in the pharmacy environment.
PMID- 25126247
TI - Delaware's Wellness Program: Motivating Employees Improves Health and Saves
Money.
AB - BACKGROUND: Every year, employers around the country evaluate their company
benefits package in the hopes of finding a solution to the ever-rising cost of
health insurance premiums. For many business executives, the only logical choice
is to pass along those costs to the employee. OBJECTIVES: As an employer, our
goal in Delaware has always been to come up with innovative solutions to drive
down the cost of health insurance premiums while encouraging our employees to
take responsibility for their own health and wellness by living a healthy and
active lifestyle, and provide them with the necessary tools. METHODS: The
DelaWELL program (N = 68,000) was launched in 2007, after being tested in initial
(N = 100) and expanded (N = 1500) pilot programs from 2004 to 2006 in which 3
similar groups were compared before and after the pilot. Employee health risk
assessment, education, and incentives provided employees the necessary tools we
had assumed would help them make healthier lifestyle choices. RESULTS: In the
first pilot, fewer emergency department visits and lower blood pressure levels
resulted in direct savings of more than $62,000. In the expanded pilot, in all 3
groups blood pressure was significantly reduced (P <.001) from preprogram to
postprogram; body fat reduction was also significant (P <.001); and glucose
levels dropped (P <.001) in 2 groups. The overall saving was about $450,000. And
in only about 4 months this year, 729 employees participating in DelaWELL had a
combined weight loss of 5162 lb. CONCLUSIONS: Decision makers in the State of
Delaware have come up with an innovative solution to controlling costs while
offering employees an attractive benefits package. The savings from its employee
benefit program have allowed the state to pass along the savings to employees by
maintaining employee-paid health insurance contributions at the same level for
the past 3 years. DelaWELL has already confirmed our motto, "Although it may seem
an unusual business investment to pay for healthcare before the need arises, in
Delaware we concluded that this makes perfect sense." This promising approach to
improving health and reducing healthcare costs could potentially be applied to
other employer groups.
PMID- 25126248
TI - Switching to generic antiepileptic drugs: growing concerns.
PMID- 25126249
TI - The better quality information to improve care for medicare beneficiaries
project: exploring approaches to physician performance measurement.
AB - On August 22, 2006, President Bush issued an Executive Order calling on all
federal agencies and those who do healthcare business with the government to
engage in collaborative efforts to incorporate the 4 cornerstones of value-driven
healthcare: health information technology standards, quality standards, price
standards, and incentives. The Department of Health and Human Services has
embarked on a campaign to make these 4 cornerstones a reality by encouraging the
public and private sectors to work collaboratively at the local level. In support
of this campaign, the Centers for Medicare & Medicaid Services launched a project
in late 2006 that leverages local collaboratives as a means to explore a national
approach to physician performance measurement. This project, which is known as
the Better Quality Information to Improve Care for Medicare Beneficiaries
Project, aims to test methods to aggregate Medicare administrative data with data
from commercial health plans and, in some cases, Medicaid, in 6 local
collaboratives to calculate and report quality measures for physician groups and
for some individual physicians.
PMID- 25126251
TI - Potayto-Potahto? The Meaning of the FDA's "Complete Response" Letters.
PMID- 25126250
TI - Emerging trends in outsourcing healthcare: medical tourism.
PMID- 25126253
TI - e-Prescribing: Stakeholders Collaborating to Reduce Medication Errors.
PMID- 25126252
TI - Chronic obstructive pulmonary disease: an overview.
AB - Chronic obstructive pulmonary disease is a growing healthcare problem that is
expected to worsen as the population ages and the worldwide use of tobacco
products increases. Smoking cessation is the only effective means of prevention.
Employers are in a unique position to help employees stop smoking. During the
long asymptomatic phase, lung function nevertheless continues to decline;
therefore, many patients seek medical attention only when they are at an advanced
stage or when they have experienced an acute exacerbation. To help preserve
patients' quality of life and reduce healthcare costs related to this chronic
disease, clinicians need to accurately diagnose the condition and appropriately
manage patients through the long course of their illness. This article discusses
the current approach to patient management.
PMID- 25126254
TI - Cutting through the politics: presidential candidates' healthcare platforms and
impact on health benefits.
AB - Healthcare reform is one of the top issues for the presidential elections this
year, and both candidates have proposed a wide range of health policy changes
that could be the most important changes to the delivery of care in the country
since the creation of Medicare and Medicaid in the 1960s. This article provides a
summary analysis of the healthcare platforms of the presidential candidates.
Specifically, the major components of their published health plan proposals are
broken out and compared using the language and descriptions from the candidates.
The article also highlights several healthcare reform proposals from health
advocacy organizations, as well as insights from medical directors and pharmacy
directors across more than 50 major managed care health plans. By framing the
issues, the article provides a basis for consideration of more detail as
healthcare reform recommendations are developed by Congress in 2009.
PMID- 25126255
TI - Medication therapy management goes hi-tech: implementing automated software
improves pharmacy efficiency.
AB - BACKGROUND: With the Centers for Medicare & Medicaid Services mandate that all
Medicare Part D benefit sponsors must offer members a medication therapy
management program, pharmacists were facing new challenges of data collecting
using software applications that had limited use for the new program. OBJECTIVE:
Health Net pharmacists initiated an automated software application to increase
the efficiency of the medication therapy management program, the integrity of the
member profiles, and the ability to provide accurate reporting of drug-related
issues. METHODS: Pharmacists were integral contributors to the automated software
program; they developed the clinical algorithms, screen layout and transitions,
and program functionality. Together with a programming company-Cognizant
Technology Solutions-they created a web-based software application to accommodate
an increasing number of eligible members and ensure accuracy of the information;
they also performed testing of the final product. RESULTS: The new program
includes member demographics and qualifying parameters that are uploaded monthly.
All drug-related problems are now displayed and updated automatically by the
software application. Assessment questions are answered and saved within the
software, and reporting functions allow for quick and accurate results.
Consequently, the number of drug regimen reviews and drug problems identified has
increased by more than 300%. CONCLUSION: The automated software application is
capable of maintaining and updating medication claims, sending and receiving
faxes to physicians and pharmacies, and allows for documentation of patient
specific freeform text. Each profile is extensive and allows the pharmacist to
get all necessary information from a single source.
PMID- 25126256
TI - Presidential candidates strong supporters of greater access to generics and
biosimilars.
PMID- 25126258
TI - New reporting system for potential safety concerns of drugs on the market.
PMID- 25126257
TI - Cost-effectiveness of second-generation antihistamines and montelukast in
relieving allergic rhinitis nasal symptoms.
AB - OBJECTIVE: Allergic rhinitis imposes a significant health and economic burden
both on individuals and the healthcare system. Second-generation prescription
antihistamines, levocetirizine, fexofenadine, and desloratadine, and the
leukotriene receptor antagonist, montelukast, differ in their ability to relieve
common rhinitis symptoms. The purpose of this study was to compare the cost
effectiveness of prescription agents based on their effectiveness in relieving
nasal symptoms. METHODS: Effectiveness was measured as the composite of nasal
symptoms, including congestion, rhinorrhea, and sneezing, from clinical studies
that compared each of the 4 comparators to placebo. Direct costs included
prescription therapy and rhinitis-related physician office visits. Physician
office visit costs were collected from an analysis of the PharMetrics insurance
claims database. Sensitivity analyses were conducted using a Monte Carlo
simulation to assess the robustness of the average and incremental cost
effectiveness ratios. RESULTS: The cost per clinically significant improvement of
nasal symptoms for levocetirizine was less than for the other model comparator
agents. The incremental cost-effectiveness ratio for levocetirizine dominated
montelukast and desloratadine and was lower than either branded or generic
fexofenadine. CONCLUSION: Levocetirizine is a cost-effective therapy for the
relief of nasal symptoms of allergic rhinitis.
PMID- 25126260
TI - e-Prescribing: A Move Toward Appropriate Medication Use.
PMID- 25126259
TI - Evaluation and management of diabetes mellitus.
AB - Diabetes mellitus is a major public health problem with tremendous medical and
economic burdens. It is the seventh leading cause of death and the number one
cause of end-stage renal disease, adult blindness, impotence, and nontraumatic
lower-limb amputation in the United States. People with diabetes are 2 to 4 times
more likely to suffer from stroke or from cardiovascular disease, and are twice
as likely to die compared with age-matched individuals without diabetes. Diabetes
cost the United States around $174 billion in 2007, $58 billion of which was
related to disability, work loss, and early mortality. Although there is
currently no known cure for diabetes, much progress has been made over the past 2
decades to improve the diagnosis and management of diabetes. Evidence has shown
that applying aggressive interventions early can prevent or delay progression to
microvascular complications that increase the mortality rate in diabetes. The
authors review the guidelines for optimal evaluation of diabetes mellitus and
discuss the current and emerging therapeutic options available in the United
States.
PMID- 25126261
TI - Focus on lowest net cost drug reduces costs for patients, plan sponsors.
PMID- 25126262
TI - Erythropoiesis-stimulating agents in a meta-stable state: guidelines, economics,
and policy in flux.
AB - Medicare coverage of erythropoiesis-stimulating agents is a complex issue with
implications for a variety of healthcare stakeholders. In the first part of the
interview (see AHDB, May 2008), Samuel M. Silver, MD, PhD, examined the evolution
and clinical implications of the Medicare coverage decisions and the eventual
shift in clinical practice away from the approved indication to situations
involving quality-of-life issues. In this second part, Dr Silver discusses with
F. Randy Vogenberg, RPh, PhD, the clinical implications of the Medicare coverage
decision regarding erythropoiesis-stimulating agents, pointing out the
noneconomic reasons why transfusions can be risky to cancer patients, and how
such policy decisions can have profound implications for patients. Dr Silver
calls for new studies to be Initiated, which would be funded by the 2 major
manufacturers of these drugs, to investigate the concerns regarding tumor
progression and thromboembolic events that are potentially associated with these
expensive and potentially toxic medications. The discussion resumes where Dr
Silver explains why it would be good to compare claims data of cancer patients
who are receiving these medications and their transfusion requirements.
PMID- 25126263
TI - Role for automated communication strategies in medication adherence management.
AB - Lack of medication adherence is a prevalent problem that causes a broad range of
health-and health-economics-related issues. Adherence management is therefore an
important strategy, but it also presents its own set of challenges.
Interventional communication from care support teams at managed care
organizations and disease management and wellness programs has proved effective
at modifying patients' medication adherence and reporting behaviors. However,
these communications do not work well from an economic standpoint. It is not
economically feasible to scale call centers and the numbers of clinical and
professional staff to communicate with the increasing number of patients with
chronic diseases who require ongoing medication use. Using communication
automation to augment traditional call center outreach can help to mediate
patient medication-taking behaviors. Specific design criteria for the automation
of this interaction are discussed in this article, offering supporting data from
a recent trial of 304 elderly patients with hypertension, and showing the
benefits of using such a system for effective blood pressure monitoring, at
reduced costs.
PMID- 25126264
TI - An overview of cholesterol management.
AB - Cardiovascular disease is the leading cause of death worldwide. Elevated
cholesterol (hypercholesterolemia) and abnormal lipid profiles (dyslipidemia) are
important risk factors for the development of cardiovascular disease. This
article discusses the role of cholesterol in the body and the relationship
between different cholesterol fractions and the risk of cardiovascular disease.
The guidelines for assessment and treatment of dyslipidemia from the National
Cholesterol Education Program are outlined, and cholesterol targets and goals of
therapy are discussed. The mechanism of action, place in therapy (eg, first-line,
second-line, or add-on), and common side effects are also discussed for each of
the available classes of drugs used in the treatment of dyslipidemia.
PMID- 25126266
TI - Healthcare innovation viability: on the edge of a knife.
PMID- 25126265
TI - Promotion of medical tourism in the media creates a trend.
PMID- 25126267
TI - Why Financial Incentives Aren't Enough to Move the Needle on Compliance.
PMID- 25126269
TI - Recent slowdown in national health expenditures attributed to growing use of
generics.
PMID- 25126268
TI - Prescription copay reduction program for diabetic employees: impact on medication
compliance and healthcare costs and utilization.
AB - OBJECTIVE: To examine the impact of a value-based benefit design on utilization
and expenditures. METHODS: This benefit design involved all diabetes-related
drugs and testing supplies placed on the lowest copay tier for 1 employer group.
The sample of diabetic members were enrolled from a 9-month preperiod and for 2
years after the benefit design was implemented. Measured outcomes included
prescription drug utilization for diabetes and medical utilization. Generalized
measures were used to estimate differences between years 1 and 2 and the
preperiod adjusting for age, gender, and comorbidity risk. RESULTS: Diabetes
prescription drug use increased by 9.5% in year 1 and by 5.5% in year 2, and mean
adherence increased by 7% to 8% in year 1 and fell slightly in year 2 compared
with the preperiod. Pharmacy expenditures increased by 47% and 53% and
expenditures for diabetes services increased by 16% and 32% in years 1 and 2,
respectively. CONCLUSION: Increases in adherence and use of diabetes medications
were observed. There were no compensatory cost-savings for the employer through
lower utilization of medical expenditures in the first 2 years. Adherent patients
had fewer emergency department visits than nonadherent patients after the
implementation of this benefit design.
PMID- 25126270
TI - Partial compliance with antipsychotics increases mental health hospitalizations
in schizophrenic patients: analysis of a national managed care database.
AB - OBJECTIVE: To investigate the relationship between partial compliance with
antipsychotic medication and mental health hospitalization in managed care
patients with schizophrenia. STUDY DESIGN: We performed a retrospective
evaluation of 1499 outpatients with >=1 antipsychotic claims and a diagnosis of
schizophrenia in a managed care database (PHARMetrics). METHODS: Patients were
followed for 12 months after their initial oral antipsychotic prescribing event.
Compliance was estimated by gaps in medication therapy, medication consistency
and persistence, and medication possession ratio. Categorical and logistic
regression analyses modeled effects of compliance, age, and gender on
hospitalization risk. RESULTS: The managed care cohort had an overall
hospitalization risk of 5.9% during follow-up. Increased hospitalization risk was
associated with lower partial compliance, as measured by 3 of the 4 definitions.
Patients with a maximum gap of >30 days were 4.7 times more likely to be
hospitalized than those with a maximum gap of 0 to 10 days (P <.001). Low
medication consistency of <70% and a medication possession ratio of <70% were
significantly associated with increased risk of hospitalization (P <.001).
Logistic regression analyses indicated that hospitalization odds decreased 16.9%
(P <.001) and 18.8% (P <.001) for every 10% increase in medication possession
ratio and medication consistency, respectively. CONCLUSION: Small decreases in
compliance with antipsychotics are associated with increased hospitalization risk
among patients with schizophrenia in a managed care population.
PMID- 25126272
TI - What changes can your health plan expect from the new administration?
AB - The new administration has already begun to introduce changes in some areas of
government. To outline potential key changes to the US healthcare system and
their impact on health plans, Robert Henry and Kip Piper of AHDB asked Dan
Mendelson to draw on his experience as current president and founder of Avalere
Health, as well as on his previous role as Associate Director for Health at the
White House's Office of Management and Budget during the Clinton Administration.
Mr Mendelson focuses on what he sees as key changes that will have direct
implications for decision makers in healthcare, including (1) a greater emphasis
on plan beneficiaries' protection, and (2) increased regulatory focus on plan
operations. Plans can expect to have less government trust in actuarial
submissions and probably more oversight and supervision of the daily operation of
a plan. The triangle of quality, access, and cost will likely reflect the point
of view of the beneficiary rather than that of plan administrators. Other topics
discussed include the potential benefits of postmarketing surveillance, new
opportunities for expediting drug approvals, and the new and increasing emphasis
on comparative effectiveness research and health information technology.
PMID- 25126271
TI - Alzheimer's disease: a healthcare burden of epidemic proportion.
AB - Alzheimer's disease is the most common cause of dementia and increases in
prevalence exponentially with age, with trends in the United States likely to
worsen in ensuing decades. The pathology in Alzheimer's disease is characterized
by an increase in extracellular amyloid plaques and intraneural neurofibrillary
tangles, with neuronal destruction in several areas of the brain, and
biochemically by a deficiency in acetylcholine; clinical manifestations include
progressive loss of memory, change in personality, and behavioral disturbances.
Pharmacotherapy includes the T.S. Dharmarajan Srinivas G. Gunturu use of
cholinesterase inhibitors and memantine; addressing the many behavioral
manifestations of the disease, especially in advanced stages, imposes tremendous
burden to caregivers and healthcare resources.
PMID- 25126273
TI - Patient cost-sharing on the rise: results from the benefit design index.
AB - OBJECTIVE: The relationship between healthcare insurers and employers plays a
critical role today in decisions about benefit design, cost-sharing, and even the
coverage of individual products and services. To better understand how these 2
stakeholders interact in the creation of healthcare benefit design, the Zitter
Group conducted a large national study of insurer-employer relationship. METHODS:
This study is based on a primary web-based survey with 100 top decision makers in
large national and important regional commercial managed care plans, and a
similar survey of 100 employers and employer benefit consultants, including
medical directors and benefit decision makers. This article reviews the results
of this research, especially in relation to insurer and employer opinions on
patient cost-sharing. RESULTS: Findings from this study show that cost-shifting
remains the prevailing cost-containment strategy used by insurers and employers.
These stakeholders expect that additional cost-shifting will have minimal impact
on patient health outcomes. CONCLUSION: Despite accumulating evidence that cost
shifting leads to undesirable health and cost consequences and has largely failed
to slow health cost growth, employers and insurers will likely continue to rely
on this modality as their primary cost-containment strategy.
PMID- 25126274
TI - Will 2009 usher in the era of biogenerics?
PMID- 25126275
TI - Employer-based health initiative: impact on employees' cardiovascular outcomes.
AB - BACKGROUND: Cardiovascular disease is the primary cause of mortality among men
and women in the United States. The Ready, Set, Goal program was an employer
based initiative designed to identify individuals at risk for cardiovascular
disease and to offer an intervention to alter those risk factors. The program
involved cardiovascular education, screening, behavior-change incentives,
continuing assessment, and follow-up. Pharmacologic treatment was not part of the
intervention. OBJECTIVE: To analyze the effects of the Ready, Set, Goal pilot
program in 5 employers in the United States on salient cardiovascular end points
for employees who completed the program. METHODS: The analysis used a
pretest/posttest within-subjects design to compare baseline measurements with
measurements for all subjects who completed a second assessment 6 months after
baseline measurements. Enrollment began in June 2004 in the first site and in May
2005 in the last site; it ended in January 2006. Patient clinical data from the
pilot interventions were aggregated to assess the effects of the intervention on
salient cardiovascular end points for individuals who completed the Ready, Set,
Goal program. Changes in short-term cardiovascular risk factors were evaluated.
Descriptive measures with paired t-tests (alpha = 0.05) were calculated at the
aggregate level for each dependent variable. Range checks were conducted on all
variables for clinical validity. RESULTS: A total of 589 subjects from 5 employer
group pilot interventions completed the program. Of these, 43% were men, 60% were
white, 9% were African-American, 11% were Hispanic, and 20% were categorized as
"other." After the intervention, mean blood pressure, total cholesterol, and low
density lipoprotein cholesterol levels were significantly lower (P <.05) compared
with baseline measurements. On average, systolic blood pressure declined by 1.9
mm Hg; diastolic blood pressure by 1.3 mm Hg; total cholesterol decreased by 5.2
mg/dL and low-density lipoprotein cholesterol by 3.4 mg/dL. Triglyceride levels
increased and high-density lipoprotein levels decreased, although these changes
were not significant, and neither were the mean increases in body weight. But
increases in body mass index were significant. CONCLUSIONS: A worksite
cardiovascular health program can have positive effects on salient cardiovascular
end points for employees. The increases in triglyceridnes and body mass index
should be further explored.
PMID- 25126277
TI - The paradox of public policy reform: change or continuum?
PMID- 25126278
TI - Are you kidding me? Clinical comparative effectiveness or evidence-based
medicine.
PMID- 25126276
TI - Methicillin-Resistant Staphylococcus aureus: A Growing Risk in the Hospital and
in the Community.
AB - Methicillin-resistant Staphylococcus aureus is a common and continuously growing
cause of nosocomial and community-acquired infections. The type, disease
severity, and clinical outcomes of these infections, as well as the genotypic and
susceptibility patterns of the bacteria differ according to the setting in which
the infection occurs-a healthcare facility or the community setting. The
incidence of these infections in the community setting has been growing
consistently in the past decade or so. In addition, resistance to the many
current antibiotics used to treat these infections is also growing, further
complicating management. Rapid-diagnosis tests and new therapeutic agents are
constantly under investigation. The authors review the current understanding of
the epidemiology, clinical manifestations, and management of methicillin
resistant Staphylococcus aureus infection, including the growing problem of
resistance. In addition, they discuss promising diagnostic and therapeutic
alternatives, as well as new control strategies to prevent its transmission or
the development of infection among carriers.
PMID- 25126280
TI - New legislations on generics and biosimilars brewing in congress.
PMID- 25126279
TI - MIPPA: First Broad Changes to Medicare Part D Plan Operations.
AB - In July 2008, as part of broad Medicare reform, Congress passed the first major
legislative changes to Medicare Part D since its enactment in 2003-the Medicare
Improvements for Patients and Providers Act. This new legislation has significant
implications for how Part D plans can market and enroll Medicare beneficiaries.
The new legislation also strengthened beneficiary protections, expanded the low
income subsidy provisions originally included in Part D, and expanded Part D
coverage. These changes have significant implications for the operation of Part D
plans and can affect those involved in benefit design, including specialty
pharmacy coverage. This article discusses the major changes that took effect on
January 1, 2009, and have immediate implications for Part D plan sponsors,
including Medicare Advantage plans and stand-alone prescription drug plans.
PMID- 25126281
TI - ProvenCare: Geisinger's Model for Care Transformation through Innovative Clinical
Initiatives and Value Creation.
AB - Geisinger's system of care can be seen as a microcosm of the national delivery of
healthcare, with implications for decision makers in other health plans. In this
interview, Dr Ronald A. Paulus focuses on Geisinger's unique approach to patient
care. In its core, this approach represents a system of quality and value
initiatives based on 3 major programs-Proven Health Navigation (medical home);
the ProvenCare model; and transitions of care. The goal of such an approach is to
optimize disease management by using a rational reimbursement paradigm for
appropriate interventions, providing innovative incentives, and engaging patients
in their own care as part of any intervention. Dr Paulus explains the reasons
why, unlike Geisinger, other stakeholders, including payers, providers, patients,
and employers, have no intrinsic reasons to be concerned with quality and value
initiatives. In addition, he says, an electronic infrastructure that could be
modified as management paradigms evolve is a necessary tool to ensure the
healthcare delivery system's ability to adapt to new clinical realities quickly
to ensure the continuation of delivering best value for all stakeholders.
PMID- 25126282
TI - The integrated patient-centered medical home: tools for transforming our
healthcare delivery system.
PMID- 25126284
TI - Prioritizing healthcare resources to keep the baby boomers out of nursing homes.
PMID- 25126283
TI - Increased Patient Cost-Sharing, Weak US Economy, and Poor Health Habits:
Implications for Employers and Insurers.
AB - Many healthcare stakeholders, including insurers and employers, agree that growth
in healthcare costs is inevitable. But the current trend toward further cost
shifting to employees and other health plan members is unsustainable. In 2008,
the Zitter Group conducted a large national study on the relationship between
insurers and employers, to understand how these 2 healthcare stakeholders
interact in the creation of health benefit design. The survey results were
previously summarized and discussed in the February/March 2009 issue of this
journal. The present article aims to assess the implications of those results in
the context of the growing tendency to increase patient cost-sharing, a weak US
economy, and poor health habits. Increasing cost-sharing is a blunt instrument:
although it may reduce utilization of frivolous services, it may also result in
individuals forgoing medically necessary care. Increases in deductibles will lead
to an overall decrease in optimal care-seeking behavior as families juggle
healthcare costs with a weak economy and stagnating wages.
PMID- 25126285
TI - The view from washington: healthcare reform.
PMID- 25126286
TI - Applying Evidence for Medical Technologies: Closing the Gap between R&D and
Decision Maker Needs.
AB - In this interview, Dr Sean Tunis, former Director of the Office of Clinical
Standards and Quality and Chief Medical Officer at the Centers for Medicare &
Medicaid Services, and current Director of the Center for Medical Technology
Policy, discusses the need to align the demands of the industry on product
development with provider and patient needs to ensure that products in the
pipeline, especially those for chronic disease care, can actually provide
clinical benefit. The question is how to make sure that new products and
technologies are not only being approved by regulatory bodies but also serve real
world needs. This will also promote the acceptance of a product or service by all
stakeholders-regulators, providers, payers, and purchasers-while meeting actual
patient needs. Another question for payers and employers is how to create a
benefit design that encourages the application of evidence in coverage decision
making toward value-based healthcare.
PMID- 25126287
TI - Biosimilars policy forum: perspectives on safety and efficacy of future products.
PMID- 25126288
TI - The working patient with cancer: implications for payers and employers.
AB - Cancer is seen today more often as a manageable chronic disease, resulting in
changing workplace characteristics of the patient with cancer. A growing number
of employees continue to work while being treated for cancer or return to work
shortly after their cancer treatment is completed. To respond to these changes
and the potential impact on the working patient's attitude, employers need
updated, factual information related to this patient population. This type of
information will support future benefit considerations by employers on employee
contributions and future employee health and productivity. In 2005, Amgen
launched a 3-year initiative to better understand cancer as a chronic disease, as
well as the impact on the working patient with cancer and on the employer. The
data from this initiative described in this article provide insights into cancer
as a chronic and manageable disease in the workforce, and the broader
implications to payers and employers.
PMID- 25126290
TI - Payer perspectives on healthcare reform.
PMID- 25126289
TI - Lower copay and oral administration: predictors of first-fill adherence to new
asthma prescriptions.
AB - BACKGROUND: Nonadherence to asthma medications is associated with increased
emergency department visits and hospitalizations. If adherence is to be improved,
first-fill adherence is the first goal to meet after the physician and patient
have decided to begin treatment. Little is known about first-fill adherence with
asthma medications and the factors for no-fill. OBJECTIVE: The goal of the study
was to examine the proportion of patients who fill a new prescription for an
asthma medication and analyze characteristics associated with this first-fill.
METHODS: This retrospective cohort study linked electronic health records with
pharmacy claims. The cohort was comprised of 2023 patients aged 18 years or older
who sought care from the Geisinger Clinic, had Geisinger Health Plan pharmacy
benefits, and were prescribed an asthma medication for the first time between
2002 and 2006. The primary outcome of interest was first-time prescription filled
by the patient within 30 days of the prescription order date. Covariates examined
included factors related to the patient (ie, age, sex, and ethnicity),
comorbidities and utilization (ie, Charlson comorbidity index, number of office
visits, number of additional medications), asthma treatment (ie, delivery route,
pharmacologic class), and pharmacy copay amount. A logistic-regression model was
used to determine covariates associated with first-fill. RESULTS: The overall
first-fill rate for new asthma medications was 78%. First-fill rate was lower for
patients with a copay above the mean of $12 (odds ratio = 0.76; 95% confidence
interval, 0.58-0.99) and higher for patients prescribed oral plus inhaled
medications (versus inhaled only, odds ratio = 3.91; 95% confidence interval,
2.15-7.11). CONCLUSIONS: SEVERAL FACTORS ASSOCIATED WITH FAILING TO FILL AN
INITIAL PRESCRIPTION FOR ASTHMA CAN BE ADDRESSED THROUGH SIMPLE INTERVENTIONS:
screening for difficulties a patient may have in filling prescriptions, avoiding
nonformulary medications, and recognizing the barrier that high copays present.
In addition, for employers and policymakers, decreasing copay may improve
adherence and, therefore, asthma control.
PMID- 25126291
TI - Use pattern and off-label use of atypical antipsychotics in bipolar disorder,
1998-2002.
AB - BACKGROUND: Postmarketing surveillance that identifies patients at high risk for
receiving off-label medications will help ensure that the benefits of such
treatment outweigh the risks. Because many off-label uses have little scientific
support, tracking the extent to which they occur as well as the particular
circumstances under which they occur is important. OBJECTIVE: To describe the
drug-use pattern for patients with bipolar disorder, and to identify demographic
and clinical factors associated with off-label use of atypical antipsychotics
before US Food and Drug Administration approval for this indication. METHODS:
Using the PHARMetrics medical claims database, a total of 105,771 adult patients
with a diagnosis of bipolar disorder were evaluated during the 5-year (1998-2002)
study period. Study drugs included mood stabilizers, antipsychotics, and
antidepressants. Off-label use of an atypical antipsychotic was defined as a
patient taking olanzapine before March 2000 (when it received an indication for
bipolar disorder) or any other atypical antipsychotic during the entire study
period. Logistic regression analysis was used to determine the odds ratio of
receiving a drug off-label. RESULTS: Utilization of and reimbursement for
atypical antipsychotics increased during the 5-year period. Of the 10.5% of
patients who took atypical antipsychotics, 7.1% took these drugs off-label. In
addition, 11% of patients received lithium, 25% received other anticonvulsants,
and 34% received antidepressants. Off-label use of atypical antipsychotics was
associated with psychiatry specialist prescribers (odds ratio = 1.52; 95% CI,
1.44-1.59) and certain comorbidities, such as substance abuse (odds ratio = 1.51;
95% CI, 1.38-1.66), anxiety disorder (odds ratio = 1.20; 95% CI, 1.14-1.26),
diabetes mellitus (odds ratio = 1.26; 95% CI, 1.16-1.37), cerebral vascular
disease (odds ratio = 1.26; 95% CI, 1.10-1.45), and hypertension (odds ratio =
1.12; 95% CI, 1.05-1.20). Over time, there has been an increase in the number of
drug therapies, including atypical antipsychotics, used to treat bipolar
disorder. CONCLUSION: Because of the significant association found between
atypical antipsychotic use and several key comorbidities, it is important for
physicians to recognize these associations and weigh the risks and benefits of
atypical antipsychotics in their treatment strategies.
PMID- 25126292
TI - Predictive and prognostic models: implications for healthcare decision-making in
a modern recession.
AB - Various modeling tools have been developed to address the lack of standardized
processes that incorporate the perspectives of all healthcare stakeholders. Such
models can assist in the decision-making process aimed at achieving specific
clinical outcomes, as well as guide the allocation of healthcare resources and
reduce costs. The current efforts in Congress to change the way healthcare is
financed, reimbursed, and delivered have rendered the incorporation of modeling
tools into the clinical decision-making all the more important. Prognostic and
predictive models are particularly relevant to healthcare, particularly in the
clinical decision-making, with implications for payers, patients, and providers.
The use of these models is likely to increase, as providers and patients seek to
improve their clinical decision process to achieve better outcomes, while
reducing overall healthcare costs.
PMID- 25126294
TI - Healthcare reform, classicism, and how we treat the elderly: the politics of
epidemiology.
PMID- 25126293
TI - Estimates of commercial population at high risk for cardiovascular events: impact
of aggressive cholesterol reduction.
AB - OBJECTIVES: To model the financial and health outcomes impact of intensive statin
therapy compared with usual care in a high-risk working-age population (actively
employed, commercially insured health plan members and their adult dependents).
The target population consists of working-age people who are considered high-risk
for cardiovascular disease events because of a history of coronary heart disease.
STUDY DESIGN: Three-year event forecast for a sample population generated from
the National Health and Nutrition Examination Survey data. METHODS: Using
Framingham risk scoring system, the probability of myocardial infarction or
stroke events was calculated for a representative sample population, ages 35 to
69 years, of people at high risk for cardiovascular disease, with a history of
coronary heart disease. The probability of events for each individual was used to
project the number of events expected to be generated for this population.
Reductions in cardiovascular and stroke events reported in clinical trials with
aggressive statin therapy were applied to these cohorts. We used medical claims
data to model the cohorts' event costs. All results are adjusted to reflect the
demographics of a typical working-age population. RESULTS: The high-risk cohort
(those with coronary heart disease) comprises 4% of the 35- to 69-year-old
commercially insured population but generates 22% of the risk for coronary heart
disease and stroke. Reduced event rates associated with intensive statin therapy
yielded a $58 mean medical cost reduction per treated person per month; a typical
payer cost for a 30-day supply of intensive statin therapy is approximately $57.
CONCLUSIONS: Aggressive low-density lipoprotein cholesterol-lowering therapy for
working-age people at high risk for cardiovascular events and with a history of
heart disease appears to have a significant potential to reduce the rate of
clinical events and is cost-neutral for payers.
PMID- 25126295
TI - Cost-sharing enhances cost control.
PMID- 25126296
TI - Can generics help heal our ailing healthcare system?
PMID- 25126297
TI - Impact of prescription benefit coverage limits on sevelamer hydrochloride
adherence for patients with ESRD.
AB - OBJECTIVE: To assess the impact of prescription benefit coverage on medication
adherence in Medicare-eligible members diagnosed with end-stage renal disease
taking sevelamer hydrochloride. METHODS: This pilot study involved a
retrospective analysis of patients with end-stage renal disease taking sevelamer,
with an annual cap on brand prescription drug spending compared with those
without a cap. We compared sevelamer adherence and discontinuation proportions
between the 2 groups of Medicare patients in 2003 and 2004. Medication adherence
was calculated based on the proportion of available days covered in relationship
to capped versus noncapped pharmacy benefit. RESULTS: Rate ratios showed that in
2003, the patients taking sevelamer under a capped benefit (N = 43) had 27% fewer
days of drug use compared with those (N = 88) without a capped benefit (relative
risk, 0.73; 95% CI, 0.58-0.93). Similarly, in 2004, those taking sevelamer under
the capped benefit (N = 21) had 33% fewer days of drug use compared with those (N
= 117) without a capped benefit (relative risk, 0.67; 95% CI, 0.46-0.96).
CONCLUSIONS: Medication adherence was significantly lower for patients with a
capped brand-name drug benefit. These findings provide insight into potential
drug utilization patterns, including for sevelamer, under the Medicare Part D
benefit, where members could face significant out-of-pocket expenditures once
coverage limits are reached.
PMID- 25126298
TI - Private health plans perspectives: electronic personal health records and
electronic prescribing.
AB - BACKGROUND: Patients, payers, public health researchers, medical economists, and
policymakers have all called for aggressive deployment of information
technologies to support the management of health records and prescriptions. In
response, payers of all types have been making investments in electronic systems.
OBJECTIVES: To understand, analyze, and quantify current private payer
involvement in electronic personal health records and electronic prescribing
development and implementation. METHODS: A web-based survey involving 62 private
commercial payer respondents representing more than 80 million covered lives and
16 national plans. RESULTS: Responses showed relatively high rates of
implementation of electronic personal health records among respondents (20
currently and 9 in the next 24 months), but a unanimity of agreement of
disappointing plan members' utilization of these systems. Implementation rates of
electronic prescribing systems are even higher. More than half of the respondents
reported utilization rates below 10%. CONCLUSION: The disappointing results with
the implementations of electronic systems are most likely the result of variables
exogenous to the technologies themselves. The low utilization of electronic
prescribing is most likely related to the general lack of penetration of
information technology into the work flow of most prescriber offices.
PMID- 25126299
TI - Wellness and the governing dynamics of healthcare reform.
PMID- 25126300
TI - Health plan retention and pharmacy costs of newly diagnosed patients with chronic
kidney disease in a managed care population.
AB - BACKGROUND: Chronic kidney disease is prevalent in the United States, and
diabetes and hypertension cause up to two thirds of all new cases. Many health
plans believe that these patients do not retain their health plans for a long
duration, therefore plans do not focus on prevention for this disease. OBJECTIVE:
To determine health plan retention rates and direct healthcare costs of adults
with newly diagnosed chronic kidney disease with diabetes or hypertension.
METHODS: A total of 31,917 patients with chronic kidney disease were included in
this study between January 1995 and December 2006, using a managed care database.
Patients were divided into 3 subgroups for cost comparison-patients with chronic
kidney disease only (n = 8836), those with chronic kidney disease with diabetes
(n = 11,252), and patients with chronic kidney disease with hypertension (n =
20,836). Follow-up of patients from index period of initial kidney disease
diagnosis was 5 years. Average enrollment duration was 38 months; 60% of all
patients remained enrolled at 3 years postdiagnosis. RESULTS: On average,
patients with chronic kidney disease and diabetes and those with chronic kidney
disease and hypertension remained enrolled slightly longer than chronic kidney
disease-only patients (39 months, 40 months, and 36 months, respectively). The
largest number of claims was for inpatient medical, followed by pharmacy and
laboratory. Mean annual direct healthcare costs were higher for patients with
chronic kidney disease and diabetes ($20,165) and those with chronic kidney
disease and hypertension ($17,612) compared with patients with chronic kidney
disease only ($9390). CONCLUSION: The study findings indicate that most patients
who are newly diagnosed with chronic kidney disease retain their health plan
affiliation for a considerable period, including those with diabetes or
hypertension. Increased direct healthcare costs were associated with the presence
of comorbidities in patients with chronic kidney disease.
PMID- 25126301
TI - Management tools for molecular diagnostic testing: financial and clinical
implications.
PMID- 25126302
TI - Increases in Drug Utilization and Patent Expirations: A Recipe for Growth of
Generics' Market Share, despite Stalling on Biosimilars.
PMID- 25126303
TI - Quality improvement initiatives: the missed opportunity for health plans.
AB - BACKGROUND: The increase in healthcare cost without direct improvements in health
outcomes, coupled with a desire to expand access to the large uninsured
population, has underscored the importance of quality initiatives and
organizations that provide more affordable healthcare by maximizing value.
OBJECTIVES: To determine the knowledge of managed care organizations about
quality organizations and initiatives and to identify potential opportunities in
which pharmaceutical companies could collaborate with health plans in the
development and implementation of quality initiatives. METHODS: We conducted a
survey of 36 pharmacy directors and 15 medical directors of different plans
during a Managed Care Network meeting in 2008. The represented plans cover almost
74 million lives in commercial, Medicare, and Medicaid programs, or a combination
of them. RESULTS: The responses show limited knowledge among pharmacy and medical
directors about current quality organizations and initiatives, except for quality
organizations that provide health plan quality accreditation. The results also
reveal an opportunity for pharmaceutical companies to collaborate with private
health plans in the development of quality initiatives, especially those related
to drug utilization, such as patient adherence and education and correct drug
utilization. CONCLUSION: Our survey shows clearly that today's focus for managed
care organizations is mostly limited to the organizations that provide health
plan quality accreditation, with less focus on other organizations.
PMID- 25126305
TI - Orphan drug pricing and payer management in the United States: are we approaching
the tipping point?
AB - The Orphan Drug Act of 1983 paved the way for the development of drugs that treat
rare diseases, defined in the United States as those affecting fewer than 200,000
patients. Orphan drugs can cost hundreds of thousands of dollars annually, but
insurers have traditionally covered these therapies because the small populations
involved did not typically lead to significant cost exposure. Payer sensitivity
to the cost of orphan drugs is rising, however, with the accelerated rate of new
launches of these agents amid intensified economic pressure. Payers are showing
increasing levels of concern and scrutiny about coverage of orphan drugs. A new
payer survey conducted between February 2008 and March 2009 provides insights on
how payers are managing orphan drugs and the way it is likely to evolve in the
future. Survey findings show that the patient share of orphan drug costs is
rising and is expected to continue to rise, barring sweeping changes in public
health policy. This shift in benefit design could affect patient access to orphan
agents and, therefore, drug utilization. Manufacturers will have to invest in
research to understand payer impact on the uptake of their orphan drugs in
development. They will also benefit from being prepared to develop strategies to
ensure patient access to and affordability of their orphan agents.
PMID- 25126304
TI - Economic Evaluation of Quality-of-Life Improvement with Second-Generation
Antihistamines and Montelukast in Patients with Allergic Rhinitis.
AB - BACKGROUND: Allergic rhinitis causes significant economic losses and substantial
reductions in quality of life. Improving a patient's symptoms can therefore
enhance the patient's quality of life. OBJECTIVE: To measure the relative cost
effectiveness of prescription second-generation antihistamines (levocetirizine,
desloratadine, and fexofenadine) and montelukast based on their impact on quality
of life in patients with uncomplicated allergic rhinitis. METHODS: A
retrospective, cost-effectiveness model was constructed using 1-year costs to
managed care payers and using the Rhinoconjunctivitis Quality of Life
Questionnaire to measure the quality of life in patients taking prescription
second-generation antihistamines or montelukast for the treatment of allergic
rhinitis. Clinical trial results for levocetirizine, desloratadine, fexofenadine
(brand and generic), or montelukast were combined as standardized mean
differences to create a pooled effectiveness measure. The costs of prescription
drugs and physician office visits for allergic rhinitis were used as direct costs
measures. Sensitivity was assessed by a Monte Carlo simulation run 1000 times.
RESULTS: All the drugs in the study showed significant improvement in quality of
life, with levocetirizine showing the greatest improvement. The incremental cost
effectiveness of levocetirizine dominated montelukast (incremental cost-effective
ratio, -1317; 95% confidence interval, -7471, -212). The incremental cost
effectiveness favored levocetirizine compared with desloratadine and branded
fexofenadine. CONCLUSION: There are significant differences in the cost
effectiveness of various oral prescription agents with regard to improving
quality of life of patients with allergic rhinitis.
PMID- 25126306
TI - Competition from biosimilars an incentive for innovation.
PMID- 25126307
TI - Physicians' perceptions of reimbursement as a barrier to comprehensive diabetes
care.
AB - BACKGROUND: As the incidence of diabetes increases, there is growing concern
about the adequacy of reimbursement levels for delivering comprehensive diabetes
care. OBJECTIVE: To investigate physicians' perceptions of the adequacy of
reimbursement, as well as resources (eg, staff, facilities, materials), for their
treatment of diabetic patients. METHODS: A qualitative exploration using a Web
based survey of 300 physicians (200 primary care providers and 100
endocrinologists) and an online discussion group of 12 physicians, focusing on 10
services recommended by the American Diabetes Association that may be prone to
underreimbursement. The 10 services were matched with 4 general diabetes care
categories to assess the adequacy of care delivery. RESULTS: The majority of
physician study participants perceived that most of the 10 identified services
are inadequately reimbursed-83% to 95% of physicians said Medicaid reimbursement
was inadequate, 75% to 89% for Medicare reimbursement, and 67% to 86% for private
insurance reimbursement-leading them to spend less time with each patient. This
reduction in time was a limiting factor to providing comprehensive diabetes care.
The survey also revealed differences between endocrinologists and primary care
physicians; for example, medical nutrition therapy was offered by 50% of
endocrinology practices compared with only 29.5% of primary care practices.
CONCLUSION: This study confirms previous findings that physicians perceive
current reimbursement for diabetes care as too low, which limits their ability to
perform all the tasks necessary to deliver comprehensive diabetes care.
PMID- 25126309
TI - Pharmacogenomics and drug development.
PMID- 25126308
TI - Hypertension management: an update.
AB - Hypertension is a significant and costly public health problem. It is a major,
but modifiable contributor for the development of cardiovascular disease.
Randomized controlled trials have shown that controlling hypertension reduces the
risk of stroke, coronary artery disease, congestive heart failure, end-stage
renal disease, peripheral vascular disease, as well as overall mortality. The
risk of developing these hypertension-related complications is continuous,
starting at a blood pressure level as low as 115/75 mm Hg. Despite the inherent
health risks associated with uncontrolled hypertension, elevated blood pressure
remains inadequately treated in the majority of patients. This article reviews
guidelines for optimal evaluation of hypertension and current therapeutic options
available to combat this common yet pervasive disease.
PMID- 25126310
TI - Obesity: effective treatment requires change in payers' perspective.
AB - BACKGROUND: Obesity is an increasing problem in the United States, and the health
problems attributed to it have a significant economic impact on the healthcare
system, as well as on patients' quality of life. In addition, childhood obesity
is increasingly becoming a prominent diagnosis. OBJECTIVE: To identify physician
and payer reactions to the profiles of 4 new obesity products in development and
the potential that these will be prescribed by physicians and reimbursed by
payers. This article examines payers' and physicians' perspectives in effective
treatment options for this epidemic. METHOD: A 2008 online survey conducted by
Reimbursement Intelligence was completed by 42 physicians who are advisors to
Pharmacy & Therapeutics Committees and see an average of 435 obese patients
monthly, as well as 17 payers who represent more than 100 million covered lives.
This research was double blinded to conceal product and client identification.
Qualitative and quantitative data were collected from the survey responses.
RESULTS: Based on the physician and payer survey responses, morbid obesity is
expected to grow in the next 2 years. About 80% of morbidly obese patients have
type 2 diabetes, but more than 75% of payers do not track patients who are obese,
morbidly obese, or those with the metabolic syndrome. Despite its effect on
business productivity and the cost of care, healthcare professionals and payers
continue to have varying perspectives related to its prevention and treatment.
Physicians would like to have more treatment options, but payers perceive them as
ineffective and find the safety and adverse effect profiles unfavorable.
CONCLUSION: There is a clear need for multiple treatment alternatives to combat
obesity that include plan member access to weight-loss options, such as
prescription medications and bariatric surgery. There needs to be an increase in
educational support from manufacturers of products for obesity, as well as
increased awareness of products in the pipeline.
PMID- 25126311
TI - Health insurance premium increases for the 5 largest school districts in the
United States, 2004-2008.
AB - BACKGROUND: Local school districts are often one of the largest, if not the
largest, employers in their respective communities. Like many large employers,
school districts offer health insurance to their employees. There is a lack of
information about the rate of health insurance premiums in US school districts
relative to other employers. OBJECTIVE: To assess the change in the costs of
healthcare insurance in the 5 largest public school districts in the United
States, between 2004 and 2008, as representative of large public employers in the
country. METHODS: Data for this study were drawn exclusively from a survey sent
to the 5 largest public school districts in the United States. The survey
requested responses on 3 data elements for each benefit plan offered from 2004
through 2008; these included enrollment, employee costs, and employer costs.
RESULTS: The premium growth for the 5 largest school districts has slowed down
and is consistent with other purchasers-Kaiser/Health Research & Educational
Trust and the Federal Employee Health Benefit Program. The average increase in
health insurance premium for the schools was 5.9% in 2008, and the average annual
growth rate over the study period was 7.5%. For family coverage, these schools
provide the most generous employer contribution (80.8%) compared with the
employer contribution reported by other employers (73.5%) for 2008. CONCLUSIONS:
Often the largest employers in their communities, school districts demonstrate a
commitment to provide choice of benefits and affordability for employees and
their families. Despite constraints typical of public employers, the 5 largest
school districts in the United States have decelerated in premium growth
consistent with other purchasers, albeit at a slower pace.
PMID- 25126312
TI - First anti-inflammatory generic drug promising new therapy for diabetes.
PMID- 25126313
TI - Evolving trends in insulin delivery in pursuit of improvements in diabetes
management.
AB - Diabetes mellitus affects 23.6 million Americans and its incidence is rapidly
increasing, particularly in older, overweight patients. Large-scale studies
conclusively show that elevated blood glucose levels are associated with an
increased risk for microvascular complications, such as retinopathy and
nephropathy. The high rates of morbidity and mortality associated with this
disease, and the costs associated with it, underscore the importance of effective
glycemic control. Conventional syringe/vial insulin delivery is associated with
many barriers for patients with diabetes mellitus and for their healthcare
providers. Substantial developments in insulin delivery show promise in
overcoming these barriers. New technologies in insulin delivery focus on
increasing patient convenience, reducing the frequency of daily injections, and
improving glycemic control. This article outlines the challenges associated with
conventional insulin delivery and describes recent developments that may help to
overcome these barriers and, ultimately, could enhance glycemic control.
PMID- 25126314
TI - Healthcare costs associated with switching from brand to generic levothyroxine.
AB - BACKGROUND: Controversy exists over the true therapeutic equivalence of branded
and generic levothyroxine-the drug of choice for treating hypothyroidism-so
professional societies recommend against switching between different formulations
of the drug and suggest that patients who do switch be monitored. Payers
typically encourage switching to generic drugs because of lower drug acquisition
costs. OBJECTIVE: To evaluate the impact of switching levothyroxine formulations
on actual healthcare costs. METHODS: Patients with hypothyroidism and at least 6
months of branded levothyroxine therapy were identified from a large healthcare
claims database. Patients who subsequently switched to another levothyroxine
formulation and could be followed for 6 months postswitch were matched to
demographically similar patients who were continuous users of branded
levothyroxine. Pre- and postswitch healthcare costs for each group were compared.
RESULTS: The savings in prescription drug costs after switching from branded to
generic levothyroxine are offset by increases in costs for other healthcare
services, such that switching is actually associated with an increase, not a
decrease, in total healthcare costs. CONCLUSION: In the absence of cost-savings,
there is no clear rationale for switching patients from brand to generic
levothyroxine.
PMID- 25126316
TI - Accountable care organizations in the era of healthcare reform.
AB - Under the Patient Protection and Affordable Care Act (PPACA) of 2010, Medicare
providers, including physician groups and hospitals, will soon have the option to
form accountable care organizations (ACOs) to improve quality and efficiency. ACO
participants may share financial gains generated from improved clinical and
economic performance, provided that quality goals and patient safeguards are met.
Through future regulations, the Centers for Medicare & Medicaid Services (CMS)
must implement the ACO option no later than January 1, 2012. In this interview,
Dr Mark B. McClellan, former CMS Administrator and US Food and Drug
Administration Commissioner, discusses the extraordinary implications of the new
ACO option for improving patient care and reducing unnecessary costs.
PMID- 25126315
TI - Pay-for-Performance Initiatives: Modest Benefits for Improving Healthcare
Quality.
AB - BACKGROUND: Pay-for-performance initiatives have been suggested as a way to
improve the quality of patient care and provide incentives to improve providers'
performance. The Centers for Medicare & Medicaid Services has endorsed such
programs to improve quality of care. OBJECTIVE: To examine the state of quality
initiatives endorsed by the Centers for Medicare & Medicaid Services in which
institutions, provider groups, and physicians are awarded incentives based on
adherence to composite metrics. METHOD: A literature search was conducted using
the keywords "pay-for-performance," "quality improvement," "medical errors," and
"physician incentive plans." RESULTS: Although quality of care has improved in
healthcare settings that engage in pay-for-performance initiatives, what can be
attributed to payer-incentive programs is uncertain. Studies demonstrate that, of
the 25 hospitals classified by the Centers for Medicare & Medicaid Services to be
in the lowest decile of quality improvements, all still made significant progress
in adhering to quality metrics after participation in the study. Financial
rewards, however, were distributed based on a predetermined threshold established
by the Centers for Medicare & Medicaid Services to be given only to participants
who fell in the top 2 deciles. Penalties were incurred by the 51 hospitals that
were within the bottom 2 deciles despite making substantial improvements. At such
institutions, large minority communities and Medicaid populations comprise the
patient populations. Other pay-for-performance schemes, such as employer-based
purchasing, consumer health-spending accounts, and collaborative groups, were
studied, with little data to support definite benefits. CONCLUSIONS: Examining
rates of improvement in adherence to pay-for-performance initiatives when
determining how to distribute financial rewards should be studied alongside the
current classification by absolute deciles. By rewarding rates of improvement,
potential elimination of quality disparities for hospitals that serve large
Medicaid and minority populations can be achieved, because such organizations are
encouraged to invest in quality improvement as a result of substantial progress
made. Although alternative strategies like employer-driven value-based purchasing
and collaboratives seem promising, the long-term effects of such initiatives
still need to be studied. Creating greater financial incentives for individual
providers to participate in pay-for-performance programs for many years to come
will remain a challenge.
PMID- 25126317
TI - Expect the unexpected: a role for behavioral economics in understanding the
impact of cost-sharing on emergency department utilization.
AB - BACKGROUND: AS EMPLOYERS AND PAYERS ADDRESS INCREASING HEALTHCARE COSTS, THEY
RESORT TO THE TENETS OF CLASSICAL ECONOMICS: if one increases the price for a
service (defined as an individual's cost-sharing), then that individual's demand
for services should decrease. This, however, may not necessarily be true, and
raises the question of whether increased cost-sharing for emergency department
services will lead to decreased utilization of those services as would be
expected in classical economics. OBJECTIVE: To assess the effect of emergency
department cost-sharing on patient utilization of emergency department services.
METHOD: In 2002, we retrospectively reviewed 2001 claims and identified 797
members who have had at least 2 nonemergent visits to the emergency department.
This cohort was comprised of members with high emergency department utilization
patterns who also had potentially differing emergency department copayment
changes from one health insurance plan year to the next. Participants had to be
covered by Humana for a minimum of 12 consecutive months. Of the original cohort,
415 remained covered by Humana after the end of the first year, 322 remained
covered after the second year, and 194 after the end of the third year. After
completions of three 12-month blocks of time with appropriate claims run out, we
assessed changes in the cohort's emergency department encounters from the
previous year to the current year relative to emergency department copayment
changes, using matched pairs t-test. RESULTS: Surprisingly, in the first 12
months, reductions in emergency department copayments resulted in decreases in
patient utilization (-58.3% change, P <.007), and increases in emergency
department copayment resulted in an increased utilization (1096.0% change, P
<.001). This unexpected trend continued in the second and third periods. Overall,
in our cohort, increases in emergency department copayments were significantly
associated with increased emergency department encounters by different
individuals in each of the 3 study periods. In contrast, in the 2 groups with no
increases in emergency department copayments, utilization of these services
decreased or remained flat. CONCLUSION: When assessing the need for emergency
department services, many factors besides cost play a role in choosing to obtain
emergency department care, including individual assessments of the probability of
a given illness and the financial or temporal implications for the care sought in
terms of "gains" or "losses" relative to a reference point. Behavioral economics
can therefore play a role in understanding why healthcare consumers behave as
they do. The implications of behavioral economics need to be factored in when
considering a healthcare benefit design.
PMID- 25126318
TI - The new accountable care organizations and medicare gain-sharing program.
PMID- 25126320
TI - Enhanced Generic Utilization Saved US Healthcare $139.6 Billion in 2009.
PMID- 25126319
TI - Effectiveness of anti-tumor necrosis factor agents in the treatment of rheumatoid
arthritis: observational study.
AB - OBJECTIVE: The efficacy of anti-tumor necrosis factor therapies in rheumatoid
arthritis has been demonstrated in randomized clinical trials. The purpose of the
present study was to evaluate the effectiveness of these agents for the treatment
of rheumatoid arthritis in a real-world setting. METHOD: This retrospective chart
review included patients from 6 clinics in the United States. Eligibility
criteria included age >=18 years, diagnosis of rheumatoid arthritis, and having
been initiated with anti-tumor necrosis factor therapy (ie, adalimumab,
etanercept, or infliximab) between January 1, 2002, and November 30, 2004.
Patients were assessed for up to 2 years after therapy initiation. Primary
outcomes of interest were improvements in 4 effectiveness measures-joint pain,
joint swelling, joint stiffness, and fatigue. A total of 496 patients met the
study's inclusion criteria: 84 (16.9%) in the adalimumab group, 146 (29.4%) in
the etanercept group, and 266 (53.6%) in the infliximab group. RESULTS:
Improvement in 1 of the 4 effectiveness measures was documented in 36.8% (n = 25)
who received adalimumab, in 47.7% (n = 62) of those who received etanercept, and
in 48.7% (n = 115) of patients who received infliximab. The infliximab group was
the only cohort to demonstrate significant improvements from baseline in joint
pain, joint swelling, and joint stiffness. The adalimumab group had significant
improvement in joint pain (P = .004). No significant change in fatigue scores was
reached with any of these agents. CONCLUSION: In the real-world setting of
patients with rheumatoid arthritis, anti-tumor necrosis factor therapy shows
significant improvements in joint pain, joint swelling, and joint stiffness,
although there are differences in effectiveness in the 4 measures among the 3
agents assessed in this study.
PMID- 25126321
TI - Comparing medical cost of care for patients with metastatic breast cancer
receiving taxane therapy: claims analysis.
AB - BACKGROUND: It has been estimated that more than $8 billion is spent annually on
the management of breast cancer in the United States. The taxane chemotherapeutic
agents are cornerstones in the treatment of breast cancer, yet no study has
assessed whether the choice of a taxane affects the economic outcomes of
metastatic breast cancer treatment. OBJECTIVE: To determine if differences exist
in the medical cost of care in patients receiving taxane-based chemotherapy for
metastatic breast cancer, and to compare the use of ancillary medications (for
neutropenia, anemia, and nausea and vomiting) and their associated costs among
taxanes. METHOD: We identified women with metastatic breast cancer based on
diagnosis codes and the women's previous adjuvant chemotherapeutic regimens. Paid
medical insurance claims were captured for the 24-month study period, from
January 1, 2006, through December 31, 2007. The groups were determined according
to the specific taxane administered. Total medical costs were captured from the
date of first taxane administration to the end of data availability. Outpatient
pharmacy costs were not available. A multivariate analysis was used to evaluate
the total medical costs in each group. Median total medical costs per patient per
month during the study period were adjusted using a multiple regression analysis.
Utilization and cost of medications administered in the office or hospital for
chemotherapy-induced adverse effects were captured and adjusted with Tobit
models. RESULTS: Of the 2245 study participants, 1035 received docetaxel, 997
received generic paclitaxel, and 213 received nab-paclitaxel. On average,
patients in the nab-paclitaxel group received more doses (9.6) than those in the
generic paclitaxel (6.0) or docetaxel (4.8) groups. The multivariate analysis was
robust, explaining 72% of the variability in total medical costs across the 3
taxane groups. Median per-patient per-month total medical costs for study
participants were within approximately $800 of each other among the groups.
Generic paclitaxel had the lowest total medical costs. The total costs for
docetaxel and nab-paclitaxel were not significantly different. Nab-paclitaxel had
the lowest utilization and lowest costs associated with colony-stimulating
factors. The proportion of patients receiving erythropoiesis-stimulating agents
was not significantly different among the 3 drugs, but the costs for these agents
were significantly lower in patients receiving nab-paclitaxel than in those
receiving docetaxel. Antiemetic use was highest in the docetaxel group, but the
costs for antiemetics were not different among the 3 taxane groups. CONCLUSION:
The differences in total medical costs among the 3 taxanes were modest. Total
medical costs were lowest for patients receiving generic paclitaxel and
comparable between the docetaxel and nab-paclitaxel groups. Patients taking nab
paclitaxel received more doses than patients taking the other taxanes. Nab
paclitaxel was associated with lower utilization and costs for colony-stimulating
factors compared with generic paclitaxel and docetaxel.
PMID- 25126322
TI - The impact of healthcare reform on payers' products, provider reimbursement, and
member engagement.
PMID- 25126323
TI - The current state of bundled payments.
PMID- 25126324
TI - Assessment of medicare part d communications to beneficiaries.
AB - BACKGROUND: Older Americans receive healthcare benefits through the federal
Medicare program. The Centers for Medicare & Medicaid Services provides
comprehensive information to Medicare beneficiaries regarding benefits, plan
options, and enrollment policies primarily through the annual Medicare & You
handbook and the Medicare website. Few studies have assessed the overall
readability and, therefore, the usefulness of this handbook for adequately
educating beneficiaries. Healthcare communications written at higher levels than
the readers' comprehension levels cannot be well understood. OBJECTIVE: To
measure the readability of the 2008 Medicare & You handbook provided to all
Medicare beneficiaries. METHOD: For our analysis, the 2008 version of the
Medicare & You handbook was downloaded from the Centers for Medicare & Medicaid
Services website. Passages of >=250 words were saved individually in Windows
Notepad as text files. Shorter passages (ie, <250 words) were combined with the
next continuing passage. Each file was then uploaded into the Internet-based
Lexile analyzer (the Lexile Framework for Reading). Figures, pictures, and tables
were not included in the analysis. RESULTS: Approximately 70% of analyzed
passages were written at approximately the 5th- to 12th-grade levels (Lexile
scores: 790L-1290L), whereas 30% of the passages were written at levels above
grade 12 (Lexile scores: 1310L-1910L). CONCLUSION: Medicare beneficiaries who
have less than a high-school level education may find the passages analyzed in
this study difficult to read and comprehend as discussed, indicating the need for
simplified communication. Our study provides recommendations to improve the
handbook for better comprehension by beneficiaries.
PMID- 25126326
TI - FDA's Approval Process Borne Out by a Large Study: But Communicating Generics'
Safety and Efficacy to the Public Leaves Much to Be Desired.
PMID- 25126325
TI - A comparison of drug formularies and the potential for cost-savings.
AB - BACKGROUND: Brand-name drug costs have been escalating in the United States, and
the reasons for this are not immediately clear. A lack of adequate and accurate
information about drug effectiveness, safety, and cost has implications for drug
utilization and cost. OBJECTIVE: To explore the extent to which health plan
formularies were consistent with recommended drug listings and identify what
would be the potential cost-savings on total drug expenditures if the utilization
rate of the recommended therapies was increased. METHOD: This study compared
publicly available recommended drug listings with the formularies of 8 major
health plans in Minnesota. Data from 1 of the health plans underwent an in-depth
case analysis to evaluate the potential impact on pharmaceutical expenditures,
using increased utilization rate scenarios of the recommended drugs. RESULTS:
Health plans were similar with respect to degree of coverage for the recommended
drugs. However, the case analysis showed that by increasing the utilization rate
of recommended drugs, a potential cost-savings of more than 50% could be realized
for the evaluated health plan for some therapeutic categories. CONCLUSION: This
study demonstrates an approach to assessing drug formularies using publicly
available, recommended drug lists that incorporated evidence for effectiveness,
safety, and cost. By using the application of this type of reliable information,
formulary changes can be guided to incentivize value-based utilization for
patient populations.
PMID- 25126328
TI - Healthcare reform: quality outcomes measurement and reporting.
PMID- 25126327
TI - Managing dyslipidemia in primary care with restricted access to lipid-modifying
therapy.
AB - BACKGROUND: Many patients with dyslipidemia do not achieve goal low-density
lipoprotein cholesterol levels. The barriers to achieving goal include inadequate
assessment of cardiovascular risk status, medication cost, formulary
restrictions, patient lack of adherence, and inadequate counseling time. Removing
barriers may improve goal attainment and reduce the risk for cardiovascular
events. OBJECTIVE: To identify opportunities to improve dyslipidemia management
in primary care by examining low-density lipoprotein cholesterol goal attainment
in patients with unrestricted or restricted access to lipid-modifying therapy.
METHOD: A total of 5936 adult patients from a primary care practice with a low
density lipoprotein measurement were categorized by coronary heart disease risk
into 1 of 4 lipid-modifying therapy groups: unrestricted (fluvastatin,
lovastatin, pravastatin, or simvastatin monotherapy); restricted (atorvastatin,
rosuvastatin, or simvastatin/ezetimibe fixed-dose combination); other (lipid
modifying combination statin therapy or a nonstatin lipid-modifying therapy); and
no lipid-modifying therapy. The primary outcome was low-density lipoprotein
cholesterol goal attainment by lipid-modifying therapy group. Logistic regression
identified associated demographic and clinical factors. RESULTS: In this cohort,
78.1% of the patients achieved low-density lipoprotein cholesterol goal levels.
Overall goal attainment rates were lower in the high and very high coronary heart
disease risk categories, at 52.6% and 31.6%, respectively. For patients at
elevated coronary heart disease risk (high or very high), the rates of low
density lipoprotein cholesterol goal attainment were 14 to 16 percentage points
higher for patients receiving restricted lipid-modifying therapy compared with
patients receiving unrestricted lipid-modifying therapy (high coronary heart
disease risk: 68% vs 52%, respectively; very high coronary heart disease risk:
42% vs 28%, respectively). Increasing age, male sex, and use of restricted lipid
modifying therapy were significantly associated with improved low-density
lipoprotein cholesterol goal attainment. Of the 1298 patients who were not at low
density lipoprotein cholesterol goal, 54.1% were not receiving any lipid
modifying therapy. For each coronary heart disease risk category, there was a
significantly higher percent utilization of unrestricted lipid-modifying therapy
compared with restricted lipid-modifying therapy (P <.001). CONCLUSION: A
significant number of patients at elevated risk for coronary heart disease remain
untreated or have low-density lipoprotein cholesterol levels above target.
Removing barriers to the use of restricted lipid-modifying agents in patients at
risk for heart disease provides an opportunity to improve low-density lipoprotein
cholesterol levels.
PMID- 25126329
TI - Implications of the new political realities on healthcare reform.
AB - With the recent change in power in the US House of Representatives that will take
effect in January, questions arise regarding potential modifications to some
features in the healthcare reform bill and its implementation. With many
provisions scheduled to take effect between 2011 and 2014, the political
implications of the elections have an immediate practical relevance to health
plans, employers, and other healthcare stakeholders. American Health & Drug
Benefits discussed some of these issues with Dan Mendelson, who served in the
Clinton administration between 1997 and 2000, when there was a similar division
of party power between Congress and the administration.
PMID- 25126330
TI - Engaging providers in medication adherence: a health plan case study.
AB - BACKGROUND: Nonadherence to treatment regimens is a common, costly, and complex
problem that is often overlooked in a busy primary care setting. OBJECTIVE: The
goals of this study were to raise providers' awareness of nonadherence among
their patients, to identify the reasons for lack of adherence, and engage
physicians in addressing these barriers. METHOD: Five primary care practices
agreed to participate. The project began in the fall of 2008 with a therapy gap
analysis, using prescription drug data from the previous 18 months to identify
nonadherent patients. Initially, 237 members were identified as potential
nonadherent patients. Each practice was presented with the data related to its
patients; the group then narrowed its sample using a chart review and/or patient
outreach. Each practice had to determine the barriers to adherence, and was then
asked to create action steps to improve patient adherence based on the group's
unique results and the specific patient population. RESULTS: Barriers to
adherence identified included prescription drug cost, multiple medications and
dosing schedules, and patient as well as family level of understanding and
acceptance of disease state. Each group gained an awareness of nonadherence as it
related to their patients. For example, in the internal medicine practice, 33% (n
= 17) of the patients reported stopping their medication because of cost. A
common reason for poor adherence in the pediatric groups was that parents decided
to stop their child's medication on weekends and in the summer, without a
physician's recommendation. Using such feedback, each practice then developed its
own methods to improve medication adherence within its patient population.
CONCLUSION: Although the final numbers in this case study were small, the
providers gained valuable insights regarding nonadherence in their practice. This
study shows the importance of engaging providers in medication adherence as a way
to improve this common problem. Making this universal issue a personal problem
for providers is key to overcoming many of the adherence barriers.
PMID- 25126331
TI - Moving beyond good intentions: making collaborative care a successful reality.
PMID- 25126332
TI - The h-e-B value-based health management program: impact on asthma medication
adherence and healthcare cost.
AB - BACKGROUND: Recent publications have shown that copayment reductions increase
medication adherence above the effects of existing disease management programs,
demonstrating an additive effect of combining a value-based insurance design with
a disease management program. This effect, however, has yet to be demonstrated
for medications used for the treatment of asthma. OBJECTIVE: To evaluate the
impact of a value-based health management asthma program-which included providing
patient education and lowering copayments for select asthma controller
medications-on medication adherence and healthcare utilization and costs. STUDY
DESIGN: The study involved a quasi-experimental intervention versus control group
design of insured patients diagnosed with asthma. METHOD: After applying the
inclusion/exclusion criteria for study participation, we obtained informed
consent from the intervention group; those eligible to participate who did not
return the forms served as the control group. The final sample size included 764
patients with asthma-298 in the intervention group and 466 in the control group.
The intervention consisted of a reduction in copayment for select asthma
controller medications from an average of $20 to $30 down to $5, as well as 3
mailings of educational materials for asthma management. Medical and pharmacy
claims data for the study population were used to evaluate all study parameters
and outcomes. Medication possession ratio was used to measure adherence to asthma
controller medications. Statistical models were used to study differences in the
2 study groups during the 12-month follow-up period for adherence and cost
outcomes. RESULTS: Participation in the value-based health management asthma
program increased patients' 12-month medication adherence by 10 absolute
percentage points in the intervention group (53.9% for intervention vs 43.9% for
control group, P <.001) and significantly decreased average monthly medical costs
($170 intervention vs $229 control, P = .004). This increase in adherence
resulted in greater monthly pharmacy costs ($181 intervention vs $124 control, P
<.001). However, the increase in pharmacy costs was offset by lower medical
costs, leading to a nonsignificant increase in average monthly total healthcare
costs ($362 intervention vs $337 control, P = .276). CONCLUSION: Adoption of a
value-based health management program that combines patient education with
lowered copayments has a positive impact on medication adherence, resulting in a
reduction in associated medical costs and no significant increase in total costs.
PMID- 25126333
TI - When information is insufficient: inspiring patients for medication adherence and
the role of social support networking.
AB - BACKGROUND: A report presented by the RAND Corporation for the Agency for
Healthcare Research and Quality recommends that patient self-management programs
should include supportive coaching, and the World Health Organization has
suggested that the enhancement of patient motivation and behavioral skills is
crucial to increasing patient care adherence. The US healthcare reform
legislation also provides incentives for evidence-based activities (eg, coaching)
that promote healthy behaviors. OBJECTIVES: To review the current research on
evidence-based coaching methods and their impact on medication adherence, as well
as offer practical applications for such coaching interventions. DISCUSSION: The
authors review the role of medication adherence in reducing the burden of chronic
diseases, using the definitions of coaching and Network Coaching as a starting
point for interventions that can enhance providers' skills in motivating patients
to improve their treatment adherence. Practical examples are included throughout
the article to illustrate the benefits of these coaching methods for patients and
providers. The mnemonic COPE is used to assist providers in the recall of 4
significant coaching and Network Coaching concepts-connectedness and
collaboration, open-ended questions, positive attitude, and encourage support.
Following COPE can reinforce physicians and pharmacists in their attempt to
improve patient medication adherence. CONCLUSION: The article presents healthcare
providers, including physicians and pharmacists, with a rationale for developing
evidence-based coaching skills and offers suggestions for the application of key
coaching concepts.
PMID- 25126334
TI - Postapproval Development Options in COPD: A Case Study in Value-Based Healthcare
Systems.
AB - BACKGROUND: Research and development activities in an era of globalization
encounter a mosaic of providers, products, services, and intermediaries;
regulatory and other government institutions; and consumers. The introduction of
novel therapeutics into this environment mandates research programs that are
relevant to the registration process, payers and purchasers, transparent pricing,
and rule-driven business practices, while providing data relevant to marketing
initiatives internationally. OBJECTIVE: To outline an example for clinical
development programs that incorporate the perspective of multiple stakeholders
into a portfolio of study designs to provide optimal data platforms that can
resonate with diverse recipients. DISCUSSION: A contract research organization
directly involved in the design, execution, and analysis of clinical trials for
new drugs and devices across pharmaceutical and biotechnology companies provides
a unique perspective regarding opportunities and challenges within the
international clinical research environment. Drs Murphy, Antonini, and Lai,
representing Worldwide Clinical Trials, utilize chronic obstructive pulmonary
disease as a demonstration project exploiting its prevalence, direct and indirect
costs, and the rapid infusion/diffusion of innovative therapy into practice as a
rationale for focus, and illustrate methods of informing registration and
technology assessments during a prototypical development process. CONCLUSION: By
virtue of its chronicity, prevalence, and pattern of healthcare utilization,
chronic obstructive pulmonary disease provides an ideal case for illustrating the
application of clinical trial methodology that can facilitate data evaluation
through the prism of multiple stakeholders. Adding an international dimension
exacerbates system complexity and serves to illustrate the breadth of issues that
can be addressed within this therapeutic area.
PMID- 25126335
TI - Perspectives in value-based insurance design for patients with diabetes:
assessment and application.
AB - BACKGROUND: Value-based insurance design initiatives have been developed in an
effort to reduce long-term healthcare costs and improve health quality. Value
based insurance design promotes the use of services or therapies that have been
shown to have clinical benefits that outweigh the cost, such as encouraging
medication adherence, and discourages those that produce results that do not
justify the cost. OBJECTIVE: The goal of this analysis is to determine the impact
of value-based insurance design as it relates specifically to drug therapy,
including adherence, for patients with diabetes. METHOD: This article analyzes
data collected by Milliman, a large actuarial group, using MedStat claims,
National Health and Nutrition Examination Surveys, and its own 2008 health cost
guidelines to develop an actuarial assessment of value-based insurance design
programs for diabetes care and therapy. This assessment models the impact that
copay structures and other management techniques have on adherence and
incremental costs. The model provides a framework for assessing the value of
benefits and directs patients toward cost-effective services supported by strong
evidence-based medicine. DISCUSSION: Analysis of actuarial modeling shows that
adjusting patient copayment designs is in line with other value-based approaches
designed to improve patient care and reduce long-term costs. Evidence from value
based insurance design initiatives suggests that reducing patient copayment has
the potential to improve clinical outcomes, including medication adherence, and
reduce overall healthcare costs. CONCLUSION: This analysis, coupled with results
from other value-based insurance design initiatives and related research,
provides support for employers and health insurance plans to consider adopting
value-based insurance design programs for patients with diabetes to improve
quality of care, while potentially reducing healthcare costs.
PMID- 25126337
TI - First Generic ARB Approval Draws a Wave of Comparative Studies.
PMID- 25126336
TI - Addressing Costs and Continuity of Care through Innovative Solutions for Infused
Therapies: A Collaborative Experience with Infliximab.
AB - BACKGROUND: Infused therapies are becoming more common as pharmaceutical and
biotechnology companies increasingly focus their research and development efforts
on biologic agents. OBJECTIVE: To understand how collaborative efforts among a
health plan, providers, and specialty pharmacies can improve the efficiency of
delivering infused therapies, using the example of a pilot program in southern
Ohio for the administration of infliximab. METHODS: In October 2008, the authors
conducted one-on-one, in-person interviews with representatives of a health plan,
a specialty pharmacy, and the 3 largest gastroenterology practices in a southern
Ohio community that collaborated to develop an innovative pilot program for
delivering infliximab for patients with inflammatory bowel disease in a cost
effective manner in the office setting. The 2 health plan and 1 specialty
pharmacy representatives were directly involved with the development and
implementation of the program. Gastroenterology practice representatives included
3 practice managers, 2 infusion nurses, 2 billing managers, and 1
precertification specialist. RESULTS: The interviews revealed the opportunities
and challenges associated with managing infused therapies, as well as the
potential unintended consequences of unilateral action by health plans. As a
result of changes introduced by a local health plan in southern Ohio, 3 of the
largest gastroenterology practices in the region decided to discontinue in-office
infliximab infusions for their patients and send them to local hospital
outpatient infusion centers. However, before the implementation of this policy, a
new collaboration between the health plan, the 3 practices, and the health plan's
specialty pharmacy enabled these practices to continue to provide this medication
in their offices. This collaboration avoided cost increases to all involved by
preventing the shift of patients to hospital outpatient departments and allowing
patients to continue their care in the office setting. CONCLUSION: It will become
increasingly important for payers to develop and support cost-effective ways to
provide physicians and patients with access to infused medications. This pilot
program shows the benefits of collaboration among healthcare stakeholders to
identify innovative solutions for delivering appropriate office-based infusion
therapy. The specific approach that is most appropriate for a specific health
plan will depend on the unique local market circumstances.
PMID- 25126338
TI - Five steps healthcare leaders can take to address childhood obesity.
PMID- 25126339
TI - Comparative effectiveness research in the United States: a catalyst for
innovation.
AB - Recent calls for value in the US healthcare system have spurred an increase in
comparative effectiveness research, which generates evidence on competing
treatment options to inform healthcare stakeholders. As a large healthcare
purchaser, the federal government has made several significant investments in
comparative effectiveness research. Notably, in 2009 the American Recovery and
Reinvestment Act allocated $1.1 billion for comparative effectiveness research,
and in 2010 the Patient Protection and Affordable Care Act established a federal
institute to organize the federal investment in comparative effectiveness
research going forward. Over the past several years, comparative effectiveness
research from the public and private sectors has begun to provide a foundation
for innovation within the insurance and life sciences industries. Health plans
and other payers are experimenting with nuanced coverage and reimbursement
policies informed by comparative effectiveness evidence. Anticipating changes in
payer, patient, and provider behaviors, drug manufacturers are refocusing their
efforts on the development of novel and better-differentiated medications. As
more comparative research becomes available in the future, continued innovation
in payer and manufacturer strategies appears likely.
PMID- 25126341
TI - Recent trends in the dispensing of 90-day-supply prescriptions at retail
pharmacies: implications for improved convenience and access.
AB - BACKGROUND: Mail-service pharmacies offer consumers the convenience of
prescriptions filled with a 90-day supply of medication. Unlike mail-service
pharmacies, retail pharmacies traditionally dispensed maintenance medication
prescriptions with a 30-day supply. However, the retail landscape changed in May
2008 with Walmart's announcement of an extension of its $4 Prescription Program
to include 90-day-supply prescriptions. OBJECTIVE: To evaluate recent changes in
access to and use of 90-day-supply maintenance medications dispensed via retail
pharmacy. SUMMARY: As of the first quarter of 2007, the proportion of retail
dispensed maintenance medications with a 90-day supply (compared with all
maintenance prescriptions dispensed) among Medicare Part D plans, self-insured
employers, and private health plans was 5.1%, 5.1%, and 5.0%, respectively. As of
December 2009, this ratio had risen to 8.0% for Medicare plans and 8.1% for
commercial health plans; the ratio among employers had risen more modestly to
6.1%. Of particular interest and importance, the proportion increased similarly
for brand and for generic medications. CONCLUSION: There has been substantial
growth in 90-day prescriptions dispensed via retail pharmacy, a trend that is
likely to continue as more insurance providers adopt compatible benefit designs.
It is important to continue monitoring these trends and to identify opportunities
to rigorously evaluate their impact on medication adherence and healthcare costs.
PMID- 25126340
TI - Comparing treatment persistence, healthcare resource utilization, and costs in
adult patients with major depressive disorder treated with escitalopram or
citalopram.
AB - BACKGROUND: Major depressive disorder is the most common type of depression,
affecting 6.6% of adults in the United States annually. Citalopram and
escitalopram are common second-generation antidepressants used for the treatment
of patients with this disorder. Because citalopram is available in generic forms
that have lower acquisition costs compared with the branded escitalopram, some
health plans may provide incentives to encourage the use of the generic option.
Decisions based solely on drug acquisition costs may encourage the use of a
therapy that is less cost-effective when treatment persistence, healthcare
utilization, and overall costs are factored in. OBJECTIVE: To compare, in a real
world setting, the treatment persistence, healthcare utilization, and overall
costs of managing adult patients with major depressive disorder who are treated
with escitalopram or citalopram. METHODS: Administrative claims data (from
January 1, 2003, to June 30, 2005) were analyzed for patients with major
depressive disorder aged >=18 years. Patients filled >=1 prescriptions for
citalopram or for escitalopram (first-fill time was defined as the index date)
and had no second-generation antidepressant use during the 6-month preindex
period. Treatment persistence, healthcare utilization, and healthcare costs were
measured over the 6-month preindex and 6-month postindex periods and compared
between patients treated with citalopram or escitalopram, using unadjusted and
multivariate analyses. RESULTS: Patients receiving escitalopram (N = 10,465) were
less likely to discontinue the treatment (hazard ratio 0.94; P = .005) and switch
to another second-generation antidepressant (hazard ratio 0.83; P <.001) than
patients receiving citalopram (N = 4212). Patients receiving escitalopram were
also less likely to have a hospital admission (odds ratio 0.88; P = .036) or an
emergency department visit and had lower total healthcare costs (-$1174) and
major depressive disorder-related costs (-$109; P <.001) during the study period.
CONCLUSION: Although the drug acquisition costs are lower for generic citalopram
than for the brand-name escitalopram, patients treated with escitalopram had
better treatment persistence, lower healthcare utilization, and lower overall
costs compared with patients treated with citalopram over the study period. This
may suggest that other considerations, in addition to acquisition cost, may need
to be factored in to assess the cost-effectiveness of drug therapy.
PMID- 25126343
TI - New economic analysis zeroes in on low generic utilization and waste in medicaid.
PMID- 25126344
TI - CMS Invites Feedback on the Proposed Accountable Care Organizations Rules.
PMID- 25126342
TI - Strategies to prevent opioid misuse, abuse, and diversion that may also reduce
the associated costs.
AB - BACKGROUND: The use of prescription opioid drugs has the potential to lead to
patient abuse of these medications, addiction, and diversion. Such an abuse is
associated with increased costs because of excessive healthcare utilization.
Finding ways to minimize the risk for abuse and addiction can enhance patient
outcomes and reduce costs to patients and to payers. OBJECTIVE: To review current
strategies that may reduce the risk for misuse and abuse of opioid medications,
which in turn can enhance patient outcomes and lower costs to health insurers and
patients. DISCUSSION: Implementing approaches that will encourage the use of safe
practices (universal precautions) in pain management by providers can reduce the
risk for abuse and misuse associated with chronic pain medications, especially
opioids. These approaches include, but are not limited to, extensive physician
and patient education regarding these medications and their associated risks for
abuse; the development of prescription monitoring programs to detect physician or
pharmacy shopping; the detection of inappropriate prescribing and medical errors;
the use of physician-patient contracts concerning opioid treatment; the
requirement of presenting a photo identification to pick up an opioid
prescription at the pharmacy; urine drug toxicology screening; provisions for
safe disposal of unused opioids; referrals to pain and addiction specialists; and
potentially encouraging the use of opioid formulations aimed at reducing abuse.
CONCLUSION: Supporting such approaches by health insurers and educating providers
and patients on the risks associated with chronic pain medications can help
minimize the risk of prescription opioid abuse, addiction, and diversion; reduce
health services utilization associated with opioid abuse; improve patient
outcomes; and reduce overall costs.
PMID- 25126345
TI - The patient-centered medical home: an essential destination on the road to
reform.
PMID- 25126347
TI - Systematic health management: the time has come to do the right thing for each
person.
PMID- 25126346
TI - Utilization, spending, and price trends for short- and long-acting Beta-agonists
and inhaled corticosteroids in the medicaid program, 1991-2010.
AB - BACKGROUND: Asthma is a chronic respiratory disease that afflicts millions of
people and accounts for substantial utilization of healthcare resources in most
industrialized countries, including in the United States. However, the exact cost
and utilization of anti-asthma medications in Medicaid in the past 2 decades have
not been well studied. Considering the safety issues surrounding the long-acting
beta-agonists, guideline updates, and the increase in asthma prevalence,
understanding anti-asthma medication prescribing trends is important to payers
and patients. GOAL: The purpose of this study was to analyze the utilization and
spending trends for anti-asthmatic agents in the US Medicaid program over the
past 2 decades. METHODS: This study was based on a retrospective, descriptive
analysis of trends in utilization of and spending on anti-asthma medications,
including short-acting beta-agonists, inhaled corticosteroids, long-acting beta
agonists, and inhaled corticosteroid/long-acting beta-agonist combinations.
Quarterly utilization and expenditure data were obtained from the national
Medicaid pharmacy files provided by the Centers for Medicare & Medicaid Services
from quarter 1 of 1991 through quarter 2 of 2010. Average reimbursement per
prescription was calculated each quarter as a proxy for drug price. RESULTS: The
total number of prescriptions for the studied anti-asthma medications rose from
8.9 million in 1991 to 15.6 million in 2009, peaking at 20.8 million in 2005, the
year before Medicare and Medicaid dual-eligible beneficiaries were moved to
Medicare Part D. From 1991 to 2009, Medicaid spending on anti-asthma medications
overall rose from $180.7 million to $1.3 billion, and spending on inhaled
corticosteroid/long-acting beta-agonist combinations rose from $52.8 million in
2001-their first year on the market-to $411.7 million in 2009. The average price
per prescription has risen in all the anti-asthma drug classes: overall, spending
per prescription has increased 4-fold between 1991 and 2009, significantly faster
than the consumer price index (57.5%) over the same period. In quarter 2 of 2010,
Medicaid spent more on the combination medication fluticasone-salmeterol-$60
million-than on any other anti-asthma medication. CONCLUSION: Anti-asthma
medications are a major and growing expense for state Medicaid programs and can
be expected to be the same for Medicare Part D in the future. Increased disease
prevalence has in part contributed to the rise in pharmacotherapy cost.
Nevertheless, drug therapy is crucial for managing asthma and asthma
exacerbations.
PMID- 25126348
TI - The economic impact of delaying 5-alpha reductase inhibitor therapy in men
receiving treatment for symptomatic benign prostatic hyperplasia.
AB - BACKGROUND: Pharmacologic treatment of lower urinary tract symptoms associated
with benign prostatic hyperplasia often includes alpha-blockers and 5-alpha
reductase inhibitors. Many clinicians use alpha-blockers for rapid symptom
control, later adding 5-alpha reductase inhibitors to modify long-term disease
progression. Delaying the addition of these medications has been shown to result
in reduced clinical outcomes. The economic impact of this practice has not been
widely studied or reported to date. OBJECTIVE: The objective of this study was to
assess the economic impact of delaying initiation of concomitant 5-alpha
reductase inhibitor therapy (>=30 days) in patients receiving alpha-blockers for
lower urinary tract symptoms. METHODS: Using 2 nationally representative
databases (Integrated Health Care Information Solutions and PharMetrics), 2
retrospective analyses were conducted involving 2636 and 4260 men, respectively,
aged >=50 years treated for benign prostatic hyperplasia between 2000 and 2007.
Economic outcomes (ie, the cost of therapy and the use of healthcare resources)
were compared for adding 5-alpha reductase inhibitor therapy early (within <30
days of initiating an alpha-blocker) versus delaying these medications (>=30 days
after initiating an alpha-blocker). RESULTS: In the Integrated Health Care
Information Solutions analysis, patients in the early add-on therapy group (n =
1572) had lower benign prostatic hyperplasia-related medical costs in the
posttreatment period than those in the delayed-therapy group (n = 1064), $349
versus $618 (P <.0001). Similar trends were seen in the PharMetrics analysis-the
medical costs in the early add-on therapy group (n = 2604) and delayed group (n =
1656) were $344 versus $449, respectively (P <.001). Pharmacy costs were $1068
for the early-treatment cohort and $989 for the delayed-treatment cohort for the
Integrated Health Care Information Solutions database, yielding total costs of
$1417 and $1606, respectively, for a $189 savings per patient over the initial
year of treatment (P <.0001). In the PharMetrics analysis, pharmacy costs were
$1391 for the early-treatment cohort and $1237 for the delayed-treatment cohort,
resulting in total cost of $1735 and $1686, respectively, yielding $59 in
additional costs per patient annually for those treated early (P = .8645).
CONCLUSION: These results suggest that patients receiving 5-alpha reductase
inhibitor therapy within 30 days after initiating alpha-blocker treatment have
lower benign prostatic hyperplasia-related medical costs than those who start
combination treatment later. The increase in pharmacy costs associated with early
initiation of 5-alpha reductase inhibitor therapy resulted in total costs that
were similar or significantly lower than those of delayed combination users.
PMID- 25126349
TI - From a to z: medication cost-management strategies for disproportionate share
hospitals.
AB - BACKGROUND: Harris County Hospital District, Houston, TX, is a publicly funded
hospital system that provides care to residents of Harris County with a need
based payment system. The Harris County Hospital District pharmacy department,
with a drug budget of more than $75 million in fiscal year 2010, utilizes a
closed formulary system that is managed by the Formulary Management and
Pharmacoeconomics Service, along with the medical staff. This service is
comprised of clinical pharmacists whose goal is to provide a comprehensive, safe,
and cost-effective formulary. OBJECTIVE: To describe the unique formulary
management process at a county hospital system and what makes this process cost
effective, which may benefit pharmacy departments in institutions serving an
indigent patient population. SUMMARY: The Harris County Hospital District drug
formulary is overseen by the Pharmacy & Therapeutics committee, which is
supported by 5 therapeutic subcommittees, including antimicrobials,
cardiovascular, general formulary, central nervous system, and oncology. The
Pharmacy & Therapeutics Committee consists of a medical staff committee that is
supported by clinical pharmacists, who serve as the facilitators of these 5
subcommittees. Their responsibilities include the provision of drug information
for formulary decisions, providing parameters to govern the use of certain
medications, communicating changes to the formulary, conducting class reviews and
medication utilization evaluations, coordinating annual pharmaceutical bids,
reviewing and writing medication use policies and procedures, facilitating the
use of cost-effective medications, and monitoring the use of medications in the
hospital system. CONCLUSION: The processes incorporated by Harris County Hospital
District in its formulary management are cost-effective and may be beneficial to
other pharmacy departments, especially those institutions that serve an indigent
patient population and are interested in cost-effective management strategies.
PMID- 25126350
TI - Moving Beyond Medicare's ACOs to Accountable Care.
PMID- 25126351
TI - The business case for payer support of a community-based health information
exchange: a humana pilot evaluating its effectiveness in cost control for plan
members seeking emergency department care.
AB - BACKGROUND: As emergency department utilization continues to increase, health
plans must limit their cost exposure, which may be driven by duplicate testing
and a lack of medical history at the point of care. Based on previous studies,
health information exchanges (HIEs) can potentially provide health plans with the
ability to address this need. OBJECTIVE: To assess the effectiveness of a
community-based HIE in controlling plan costs arising from emergency department
care for a health plan's members. Albert Tzeel. METHODS: The study design was
observational, with an eligible population (N = 1482) of fully insured plan
members who sought emergency department care on at least 2 occasions during the
study period, from December 2008 through March 2010. Cost and utilization data,
obtained from member claims, were matched to a list of persons utilizing the
emergency department where HIE querying could have occurred. Eligible members
underwent propensity score matching to create a test group (N = 326) in which the
HIE database was queried in all emergency department visits, and a control group
(N = 325) in which the HIE database was not queried in any emergency department
visit. RESULTS: Post-propensity matching analysis showed that the test group
achieved an average savings of $29 per emergency department visit compared with
the control group. Decreased utilization of imaging procedures and diagnostic
tests drove this cost-savings. CONCLUSIONS: When clinicians utilize HIE in the
care of patients who present to the emergency department, the costs borne by a
health plan providing coverage for these patients decrease. Although many factors
can play a role in this finding, it is likely that HIEs obviate unnecessary
service utilization through provision of historical medical information regarding
specific patients at the point of care.
PMID- 25126353
TI - Managing utilization by exception.
PMID- 25126352
TI - Modeling costs and outcomes associated with a treatment algorithm for problem
bleeding episodes in patients with severe hemophilia a and high-titer inhibitors.
AB - BACKGROUND: No evidence-based treatment guidelines are currently available for
the treatment of problem bleedings in patients with hemophilia who develop
clotting factor inhibitors. A treatment algorithm was developed previously to
help providers optimize the approach to the treatment of this patient population.
The algorithm provides the specific intervals between treatments; however, it
does not specify dosing recommendations and does not offer insights into the
likelihood of outcome improvements at each time interval. OBJECTIVE: To develop a
model to analyze the impact on patient outcomes and costs of adhering to a
current treatment algorithm for the 2 available clotting therapies to treat
bleeding episodes in patients with hemophilia who develop clotting factor
inhibitors. METHODS: A simulation model was developed using a modified Delphi
method approach based on a consensus opinion of an expert panel. The model was
used to analyze the impact of following the available treatment algorithm on
patient outcomes and costs. Treatment patterns and the likelihood of a resolved
bleeding episode associated with following the treatment algorithm (ie,
adherence) were compared with not following the algorithm (ie, nonadherence).
This model assumed 2 scenarios in which treatment was initiated with each of the
2 bypassing agents currently available, and clinical and economic outcomes were
mapped for adhering to and not adhering to the consensus treatment algorithm.
RESULTS: The simulation model shows that adhering to the treatment algorithm
would result in 74.4% of patients improving at 72 hours compared with only 56.7%
of patients when not adhering to the algorithm. According to this model,
regardless of the bypassing agent used at initiation, adherence to the treatment
algorithm would result in fewer patients requiring combined sequential therapy
with the 2 bypassing agents for 3 days. In addition, using this analytic model,
reducing the percentage of patients with hemophilia who required combined
sequential therapy by 17.6% resulted in an average cost-savings of $16,305 per
patient. CONCLUSION: Adherence to an algorithm in which treatment is altered at
regular intervals based on a patient's clinical response has the potential to
improve patient outcomes and reduce the number of nonresponsive patients
requiring sequential therapy in patients with hemophilia who have clotting factor
inhibitors and are experiencing problem bleeding episodes. >Adherence to the
algorithm would also result in reduced costs to patients and payers.
PMID- 25126354
TI - Anticoagulation Bridging Therapy Patterns in Patients Undergoing Total Hip or
Total Knee Replacement in a US Health Plan: Real-World Observations and
Implications.
AB - BACKGROUND: The necessity for anticoagulant bridging therapy after joint
replacement surgery is widely understood, but treatment administration patterns
in the prevention of venous thromboembolism (VTE) after total hip replacement
(THR) or total knee replacement (TKR) surgery during the hospital stay have yet
to be examined. OBJECTIVE: To investigate anticoagulation thromboprophylaxis
patterns, especially the use of anticoagulant bridging therapy and/or nonbridged
treatment strategies, in patients undergoing THR/TKR surgery. METHODS: This
retrospective study was based on a large hospital database linked with outpatient
claims from 2005 through 2007. The study population included 1770 patients who
were admitted for either THR or TKR surgery and were aged >=18 years on the date
of the surgery, defined as the index date. Patients were required to have
commercial insurance or Medicare coverage and be continuously enrolled in their
health plan for at least 180 days before and 90 days after the index date. The
data were analyzed retrospectively for risk-adjusted postsurgery VTE and major
bleeding events among patients receiving anticoagulation thromboprophylaxis.
Patterns of anticoagulant bridging therapy use were also assessed. A risk
adjustment was performed using propensity score matching. RESULTS: Of 1770
eligible patients, 1551 (88%) received anticoagulant VTE prophylaxis; 264 (15%)
received combination low-molecular-weight heparin and warfarin. Of these, 105
(40%) patients were switched between the 2 monotherapies, and 159 (60%) received
bridged (overlapping) prophylaxis. The overall rates of VTE and bleeding events
were significantly lower with bridged therapy than with nonbridged therapy (5.8%
vs 18.4%, respectively, for VTE, P <.02; 2.3% vs 4.60% for major bleeding, P =
.41; 1.15% vs 8.05% for minor bleeding, P <.03). CONCLUSION: Although existing
guidelines recommend anticoagulant bridging therapy after THR or TKR surgery, the
limited data regarding anticoagulant bridging practice patterns suggest that
patients who undergo such surgery do not receive adequate anticoagulant
thromboprophylaxis immediately after discharge. Our findings suggest that
increased use of bridging therapy after THR or TKR surgery may help improve
postsurgery patient outcomes by reducing VTE and bleeding rates.
PMID- 25126355
TI - Obesity in the workplace: impact on cardiovascular disease, cost, and utilization
of care.
AB - BACKGROUND: In forecasting the future of cardiovascular disease (CVD), the
American Heart Association calls for preventive strategies with particular
attention to obesity. The association between obesity and CVD, including coronary
artery disease (CAD) and diabetes, is well established. The rising prevalence of
obesity in the workforce may have additional implications for employers and
employees besides the demonstrated effects on absenteeism and workers'
compensation. OBJECTIVE: This study was undertaken to determine the impact of
population obesity on care utilization and cost of cardiovascular conditions such
as hypertension, CAD, and cerebrovascular disease (or stroke) in a large US
population of employees engaged in a major corporate wellness program. STUDY
SAMPLE: Using data from a single large industrial employer across 29
geographically distinct worksites in the United States, 179,708 episodes of care
from 2004 to 2007 for 10,853 employees were included. METHODS: The population
based economic impact of obesity was calculated on the basis of the frequency of
episodes of care per 1000 employees and on the amount eligible for payment per
episode of care in US dollars. Data were obtained from a wellness program
databases, episode of illness inventories, and pharmacy and medical claims. High
and low prevalence rates of obesity, by obesity quartile, were used to create
linear mixed models to examine associations with disease outcomes, while
controlling for correlation within each worksite. RESULTS: Worksites with a high
rate of obesity (ie, in the fourth quartile) had 348.4 more episodes of care of
any kind per 1000 employees (P <.001), 38.6 more hypertension episodes of care
per 1000 employees (P <.001), and 2.5 more cerebrovascular disease episodes of
care per 1000 employees (P = .017) compared with worksites in the lower 3
quartiles. A worksite in the fourth obesity rate quartile had $223 greater cost
per any kind of episode (P <.001), $169 greater cost per hypertension episode (P
= .003), and $1620 more per CAD episode (P = .005) compared with worksites in the
lower 3 quartiles. The overall economic impact per 1000 employees was calculated
by combining episode frequency and eligible amount for payment per episode. For
sites in the lower 3 quartiles of obesity, the eligible amount per 1000 employees
for any kind of care was $4.01 million. However, for sites in the highest obesity
quartile, the eligible amount for payment per 1000 employees was $5.26 million.
This translates into $1250 greater cost per employee. Similar calculations were
used to evaluate the effect of obesity on the amount eligible for payment per
employee for hypertension, CAD, and cerebrovascular disease episodes, with an
estimated $69, $89, and $8 greater cost, respectively, per employee. CONCLUSION:
Worksites with greater obesity prevalence rates were associated with numerically
more frequent and more expensive episodes of care than worksites with low obesity
prevalence.
PMID- 25126356
TI - A call to action: responding to the future forecasting of cardiovascular disease
in america.
AB - BACKGROUND: Cardiovascular disease (CVD) continues to be a leading cost driver
for payers in the United States.1 The American Heart Association estimates that
more than 75 million individuals nationwide have some form of CVD. Individuals
aged 20 to 45 years are developing CVD at higher rates than ever before.
OBJECTIVES: To discuss the alarming increase in the rate of CVD in young adults
(aged 18-45 years) previously only seen in older adults (aged >=65 years) and
describe the 5 primary risk factors (smoking, obesity, hypertension, diabetes,
and dyslipidemia) that contribute to this new trend in the working-age
population. DISCUSSION: Using Medical Expenditure Panel Survey data, this article
outlines the increased prevalence of the 3 primary components of CVD-stroke,
heart failure, and myocardial infarction-in younger adults and the cost impact on
payers and on US society. The examples provided in this article highlight the
need for increased efforts by all healthcare stakeholders, and by payers in
particular, to develop prevention strategies for CVD risk factors targeted at
young adults to curb the alarming rise in CVD among this age-group. CONCLUSION:
This article provides compelling evidence for the need to institute prevention
measures to curb the growing prevalence of CVD risk factors among younger adults
in the United States.
PMID- 25126357
TI - Atypical antipsychotics and metabolic syndrome in patients with schizophrenia:
risk factors, monitoring, and healthcare implications.
AB - BACKGROUND: Metabolic syndrome is a leading cause of morbidity and mortality in
patients with schizophrenia, with a prevalence rate double that of nonpsychiatric
populations. Given the amount of evidence suggesting a link between atypical
antipsychotic medications and metabolic syndrome, several agencies have
recommended regular clinical monitoring of weight, symptoms of hyperglycemia, and
glucose in chronically medicated patients with schizophrenia. OBJECTIVES: To
summarize the current literature on atypical antipsychotic-induced metabolic
syndrome in patients with schizophrenia, outline some of the molecular mechanisms
behind this syndrome, identify demographic and disease-related risk factors, and
describe cost-effective methods for surveillance. DISCUSSION: The differential
prevalence of metabolic syndrome associated with various atypical antipsychotic
medications has been evidenced across numerous studies, with higher effects seen
for certain antipsychotic medications on weight gain, waist circumference,
fasting triglyceride level, and glucose levels. Given the association of these
symptoms, all atypical antipsychotic medications currently include a warning
about the risk of hyperglycemia and diabetes, as well as suggestions for regular
monitoring. Despite this, very little data are available to support adherence to
these monitoring recommendations. Lack of awareness and resources, diffusion of
responsibility, policy implementation, and organizational structure have all been
implicated. CONCLUSION: The treatment of schizophrenia involves a balance in
terms of risks and benefits. Failing to treat because of risk for complications
from metabolic syndrome may place the patient at a higher risk for more serious
health outcomes. Supporting programs aimed at increasing monitoring of simple
laboratory and clinical measures associated with metabolic syndrome may decrease
important risk factors, improve patients' quality of life, and reduce healthcare
costs.
PMID- 25126359
TI - Lipid management in patients with type 2 diabetes.
AB - BACKGROUND: Diabetes is correlated with a high risk for cardiovascular disease
(CVD). The management of diabetic dyslipidemia, a well-recognized and modifiable
risk factor, is a key element in the multifactorial approach to preventing CVD in
patients with type 2 diabetes. Diabetic dyslipidemia is characterized by elevated
triglyceride levels, decreased high-density lipoprotein cholesterol levels, and
elevated low-density lipoprotein cholesterol (LDL-C) levels. OBJECTIVES: To
describe the effective approach to the management of dyslipidemia in patients
with diabetes to allow providers and payers to become familiar with the treatment
goals for all the components of lipoproteins, to correctly initiate appropriate
lipid-lowering medications based on treatment goals and lipid-lowering
capability, and to apply the data presented in lipid clinical trials to the
treatment of patients with diabetes. SUMMARY: Diabetes is associated with a 2- to
4-fold increase in risk for CVD. The risk factors for coronary artery disease
(CAD) include hypertension, dyslipidemia, obesity, and smoking. Therefore,
prioritizing and managing diabetic patients with CVD risk factors is vital.
CONCLUSION: LDL-C appears to have the greatest role in premature and early
atherosclerosis and the development of CAD and must be treated as aggressively as
hyperglycemia to reduce CAD risk. Becoming familiar with lipid treatment goals
and the many therapies available today can help providers and payers implement
the appropriate approach to managing diabetic dyslipidemia risk factors and
reduce the burden of this disease.
PMID- 25126360
TI - From asheville to hickory: transforming our "sick care" system into a true
"health care" model.
PMID- 25126361
TI - The hickory project: controlling healthcare costs and improving outcomes for
diabetes using the asheville project model.
AB - BACKGROUND: The results of the Asheville Project have shown the success of a
community-based, chronic disease management model in improving clinical outcomes
in patients with chronic disease while reducing annual costs of care per
participant. The question arose whether other programs using a similar management
model and implemented in other communities could replicate the success of the
Asheville Project in improving clinical outcomes and reducing costs for patients
with a chronic disease. OBJECTIVE: To assess the long-term clinical and financial
outcomes of a chronic care management model for patients with diabetes, using the
Asheville care management model that was successful in the management of several
chronic diseases. STUDY DESIGN: Longitudinal, 3-year (2007-2009), quasi
experimental, multisite, pre-/postenrollment study. METHODS: Self-insured health
plan members with diabetes agreed to meet on a regular basis (ie, an average of
every 3 months) with a healthcare professional. Participants received reduced
copayments on diabetes-related medications and supplies as an incentive for
participating in the study. Providers utilized a web-based electronic medical
record system that provided updated medical and prescription data and highlighted
gaps in care based on national standards. Program providers included community
pharmacists, population health management company pharmacists, and nurses at on
site clinics, trained in use of evidence-based guidelines of care. Providers
assessed patients' medications, knowledge level, and lifestyle; provided patient
education and goal setting; and referred patients for physician follow-up and
recommendations to physicians. The majority of the encounters were face-to-face.
RESULTS: The study included 95 plan members in the clinical cohort participating
for 1 year or more, and 54 members in the financial cohort who have been
participating in the program for 3 years. At the end of 3 years, the percentages
of those achieving guideline goals increased from baseline to the latest follow
up included, respectively, reaching target hemoglobin A1c levels, 38% to 53%; low
density lipoprotein cholesterol, 46% to 67%; systolic blood pressure (BP), 55% to
72%; diastolic BP, 60% to 71%; annual eye examination, 37% to 61%; and self
testing blood glucose, 79% to 97%. Total healthcare costs decreased by an average
of $2704 per participant per year. The program's return on investment was $4.89
to every $1 spent (including program costs). CONCLUSION: The Hickory Project
shows that it is possible to produce sustained improvements in clinical outcomes
and reductions in healthcare costs for patients with diabetes using a chronic
care model that provides frequent patient follow-up, a focus on appropriate
medication therapy, adherence to clinical practice guidelines, and a reduction in
prescription copayments for antidiabetes medications as an incentive for patients
to participate in the program.
PMID- 25126358
TI - Current therapies and emerging drugs in the pipeline for type 2 diabetes.
AB - BACKGROUND: Diabetes is a global epidemic that affects 347 million people
worldwide and 25.8 million adults in the United States. In 2007, the total
estimated cost associated with diabetes in the United States in 2007 was $174
billion. In 2009, $16.9 billion was spent on drugs for diabetes. The global sales
of diabetes pharmaceuticals totaled $35 billion in 2010, and these are expected
to rise to $48 billion by 2015. Despite such considerable expenditures, in 2000
only 36% of patients with type 2 diabetes in the United States achieved glycemic
control, defined as hemoglobin A1c <7%. OBJECTIVE: To review some of the most
important drug classes currently in development for the treatment of type 2
diabetes. DISCUSSION: Despite the 13 classes of antidiabetes medications
currently approved by the US Food and Drug Administration (FDA) for the treatment
of type 2 diabetes, the majority of patients with this chronic disease do not
achieve appropriate glycemic control with these medications. Many new drug
classes currently in development for type 2 diabetes appear promising in early
stages of development, and some of them represent novel approaches to treatment,
with new mechanisms of action and a low potential for hypoglycemia. Among these
promising pharmacotherapies are agents that target the kidney, liver, and
pancreas as a significant focus of treatment in type 2 diabetes. These
investigational agents may potentially offer new approaches to controlling
glucose levels and improve outcomes in patients with diabetes. This article
focuses on several new classes, including the sodium-glucose cotransporter-2
inhibitors (which are furthest along in development); 11beta-hydroxysteroid
dehydrogenase (some of which are now in phase 2 trials); glycogen phosphorylase
inhibitors; glucokinase activators; G protein-coupled receptor 119 agonists;
protein tyrosine phosphatase 1B inhibitors; and glucagon-receptor antagonists.
CONCLUSION: Despite the abundance of FDA-approved therapeutic options for type 2
diabetes, the majority of American patients with diabetes are not achieving
appropriate glycemic control. The development of new options with new mechanisms
of action may potentially help improve outcomes and reduce the clinical and cost
burden of this condition.
PMID- 25126363
TI - Adapting to market changes: beyond healthcare reform.
PMID- 25126362
TI - Health Resource Utilization and Direct Costs Associated with Angina for Patients
with Coronary Artery Disease in a US Managed Care Setting.
AB - BACKGROUND: Angina is often a first symptom of coronary artery disease (CAD);
however, the specific burden of illness for patients with CAD-associated angina
in managed care has not been reported. OBJECTIVE: To determine the clinical and
cost burden of illness for patients with CAD-associated angina in a managed care
environment. STUDY DESIGN: A retrospective database analysis in a nationwide
commercial managed care plan. METHODS: This study included patients with
International Classification of Diseases, Ninth Revision, Clinical Modification
diagnostic or procedure codes for CAD between July 1, 2004, and June 30, 2006,
who had data available for the period 6 months before and 12 months after the
index date. The primary analyses for patients classified as having CAD with
angina were based on a 3-algorithm patient-identification model (combined
positive predictive value of 89%, 95% confidence interval, 0.79-0.95).
Utilization measures for the 12-month postindex period, annual CAD-related direct
costs, and total all-cause costs (ie, medical plus pharmacy) were determined. A
generalized linear model was used to compare CAD-related costs and overall costs.
RESULTS: Of the 246,227 patients with CAD, the 3-algorithm model assigned 230,919
patients (93.8%) to the CAD-without-angina cohort and 15,308 (6.2%) to the CAD
with-angina cohort. Patients with angina were more likely than patients without
angina to be hospitalized (41% vs 11%, respectively; P <.001), to visit the
emergency department (34% vs 12%, respectively; P <.001), to have office visits
(94% vs 79%, respectively; P <.001), and to have more revascularization
procedures (35% vs 8%, respectively; P <.001). Average CAD-related inpatient
costs were $9536 versus $2169, and pharmacy costs were $1499 versus $891, for
patients with and without angina, respectively. Total average CAD-related medical
and pharmacy costs for patients with angina were $14,851 versus $4449 for
patients with CAD without angina, and the average all-cause per-patient cost was
$28,590 versus $14,334, respectively. CONCLUSION: Based on these results, US
patients with CAD plus angina in a managed care setting use significantly more
healthcare services and incur higher costs than patients who have CAD without
angina. Revascularization procedures are a major driver of these increased costs
for those with CAD and angina.
PMID- 25126365
TI - The era of personalized medicine in oncology: novel biomarkers ushering in new
approaches to cancer therapy.
PMID- 25126364
TI - Review of strategies to enhance outcomes for patients with type 2 diabetes:
payers' perspective.
AB - BACKGROUND: Diabetes and its clinical consequences exact a great toll on patients
and on society in terms of its effects on morbidity and mortality and its
staggering economic impact. OBJECTIVE: To review various programs and strategies
that aim at enhancing adherence to antihyperglycemic therapy and suggest the best
approach to improving patient outcomes and reducing healthcare costs. DISCUSSION:
Treatment goals for patients with diabetes have been defined, and multiple safe
and effective medications are available. Nevertheless, the majority of patients
with diabetes fail to achieve treatment goals, because of difficulty with
adherence to medication regimens and lifestyle modifications, and because of
economic barriers. This article discusses various initiatives developed to
improve patient outcomes, including consumer-driven health plans and wellness and
prevention programs. Furthermore, economic incentives to patients, such as value
based insurance design, may increase adherence; nevertheless, evidence suggests
that such programs alone provide only modest gains. Primary providers in disease
management programs can include nurses, case managers, or pharmacists. Supportive
interventions across several modalities have been shown to be effective.
CONCLUSION: An approach that uses a combination of strategies designed to impact
patients' health-related behaviors across a variety of modalities may help to
improve outcomes and reduce costs. Additional novel, innovative interdisciplinary
initiatives are necessary to effect meaningful change that can facilitate
improved health outcomes for patients with diabetes and maximize cost
effectiveness approaches for payers.
PMID- 25126366
TI - Building Your Automated Bundled Payment for an Episode-of-Care Initiative.
PMID- 25126367
TI - Impact of Treatment by NCQA-Certified Physicians on Diabetes-Related Outcomes.
AB - BACKGROUND: The National Committee for Quality Assurance supports high-quality
care for patients through the Diabetes Recognition Program (DRP). The DRP
recognizes physicians and practices that are providing high-quality diabetes care
as determined by 10 key measures. OBJECTIVE: To examine the impact of treatment
by DRP-certified physicians compared with non-DRP-certified physicians on patient
outcomes. METHODS: This retrospective claims analysis was conducted from January
1, 2007, through November 30, 2007, using a large US database of approximately 14
million commercially insured members. Physicians with DRP certification (N =
1188) were identified and matched 1:1 to physicians without DRP certification
based on physician specialty, location (state) of practice, size of potential
patient population, and number of patients with type 2 diabetes treated by the
physician. Patients were included if they had type 2 diabetes and had been
treated by a physician in the DRP group (N = 3836) or in the comparison group (N
= 4175). Primary outcomes were medication use, medical resource utilization, and
expenditures. Per-patient per-year (PPPY) medical and pharmacy utilization
measures were analyzed using Poisson regression; PPPY expenditures were estimated
using a generalized linear model with gamma distribution. RESULTS: Multivariate
analysis showed that patients treated by DRP-certified physicians had more
postindex diabetes-related office visits (mean PPPY, 4.69 vs 4.44, respectively;
P <.001) and outpatient visits (mean PPPY, 0.93 vs 0.85, respectively; P <.001)
than patients treated by non-DRP-certified physicians, but fewer emergency
department visits (mean PPPY, 0.04 vs 0.07, respectively; P <.001) and inpatient
visits (mean PPPY, 0.08 vs 0.10, respectively; P = .02). Prescribing rates for
oral antihyperglycemic drugs and statins were higher among DRP-certified
physicians than non-DRP-certified physicians. Total diabetes-related healthcare
expenditures were lower for patients with type 2 diabetes managed by DRP
certified physicians compared with those managed by non-DRP-certified physicians
(mean PPPY, $3424 vs $4097, respectively; P = .03). CONCLUSION: Significant
differences in oral antihyperglycemic and statin drug use, and diabetes-related
emergency department and inpatient visits and expenditures, were observed in this
study between DRP-certified and non-DRP-certified physicians, showing overall
improved outcomes for patients managed by DRP-certified physicians.
PMID- 25126368
TI - Are ACOs the Answer to High-Value Healthcare?
AB - BACKGROUND: The Patient Protection and Affordable Care Act required the Secretary
of the Department of Health and Human Services to establish the Medicare Shared
Savings Program (MSSP) by January 1, 2012. The MSSP is intended to encourage
physicians, hospitals, and other providers and suppliers to form accountable care
organizations (ACOs) to provide cost-effective, coordinated care to Medicare
beneficiaries. Under the MSSP, ACOs can qualify for additional payments by
meeting specific savings benchmarks and quality measures. OBJECTIVES: To review
the anticipated changes in the role and responsibilities of ACOs and to evaluate
the challenges and opportunities that various healthcare stakeholders, including
patients, providers, and payers, will encounter with the launching of the new
MSSP. DISCUSSION: ACOs assume responsibility for overall care, cost, and quality
of patient care. The MSSP will provide ACOs additional payments for meeting cost
savings and quality benchmarks. The extra savings will be shared with
participating providers based on different risk-sharing options. As the MSSP and
new ACOs launch, stakeholders will be impacted differently. This article is
based, in part, on responses of approximately 100 payers to a survey conducted in
June 2011 by Xcenda. Each stakeholder group, including providers, payers,
patients, and manufacturers, must monitor the reactions and relationships between
all players in the care continuum. Providers will have to achieve a greater level
of coordination and collaboration than typically exists today. Government and
commercial payers will have a role in determining how quickly they will adopt
accountable care models. Patients are expected to become more engaged and
participatory in their care to achieve optimal outcomes, and manufacturers will
be required to prove the value of their products given the clinical value
proposition embedded in accountable care models. CONCLUSION: Whether ACOs are the
answer to providing higher-quality healthcare at lower costs remains unclear. All
signs, however, point toward a systemic change in an effort to improve patient
care and contain healthcare costs. It will be important for all healthcare
stakeholders to understand the roles that ACOs will play in ensuring access to
care and quality of care.
PMID- 25126369
TI - Back to School: Quality Improvement through Academic Detailing.
PMID- 25126371
TI - 2014: the year of the healthcare consumer.
PMID- 25126370
TI - Sensitivity of medication use to formulary controls in medicare beneficiaries: a
review of the literature.
AB - BACKGROUND: Several studies have examined the impact of formulary management
strategies on medication use in the elderly, but little has been done to
synthesize the findings to determine whether the results show consistent trends.
OBJECTIVE: To summarize the effects of formulary controls (ie, tiered copays,
step edits, prior authorization, and generic substitution) on medication use in
the Medicare population to inform future Medicare Part D and other coverage
decisions. METHODS: This systematic review included research articles (found via
PubMed, Google Scholar, and specific scientific journals) that evaluated the
impact of drug coverage or cost-sharing on medication use in elderly (aged >=65
years) Medicare beneficiaries. The impact of drug coverage was assessed by
comparing patients with some drug coverage to those with no drug coverage or by
comparing varying levels of drug coverage (eg, full coverage vs $1000 coverage or
capped benefits vs noncapped benefits). Articles that were published before 1995,
were not original empirical research, were published in languages other than
English, or focused on populations other than Medicare beneficiaries were
excluded. All studies selected were classified as positive, negative, or neutral
based on the significance of the relationship (P <.05 or as otherwise specified)
between the formulary control mechanism and the medication use, and on the
direction of that relationship. RESULTS: Included were a total of 47 research
articles (published between 1995 and 2009) that evaluated the impact of drug
coverage or cost-sharing on medication use in Medicare beneficiaries. Overall, 24
studies examined the impact of the level of drug coverage on medication use; of
these, 96% (N = 23) supported the association between better drug coverage (ie,
branded and generic vs generic-only coverage, capped benefit vs noncapped
benefit, supplemental drug insurance vs no supplemental drug insurance) or having
some drug coverage and enhanced medication use. Furthermore, 84% (N = 16) of the
19 studies that examined the effect of cost-sharing on medication use
demonstrated that decreased cost-sharing was significantly associated with
improved medication use. CONCLUSION: Current evidence from the literature
suggests that restricting drug coverage or increasing out-of-pocket expenses for
Medicare beneficiaries may lead to decreased medication use in the elderly, with
all its potential implications.
PMID- 25126372
TI - The economic burden of ischemic stroke and major hemorrhage in medicare
beneficiaries with nonvalvular atrial fibrillation: a retrospective claims
analysis.
AB - BACKGROUND: Understanding the economic implications of oral anticoagulation
therapy requires careful consideration of the risks and costs of stroke and major
hemorrhage. The majority of patients with atrial fibrillation (AF) are aged >=65
years, so focusing on the Medicare population is reasonable when discussing the
risk for stroke. OBJECTIVE: To examine the relative economic burden associated
with stroke and major hemorrhage among Medicare beneficiaries who are newly
diagnosed with nonvalvular atrial fibrillation (NVAF). METHODS: This study was a
retrospective analysis of a 5% sample of Medicare claims data for patients with
NVAF from 2006 to 2008. Patients with NVAF without any claims of AF during the 12
months before the first (index) claim for AF in 2007 (baseline period) were
identified and were classified into 4 cohorts during a 12-month follow-up period
after the index date. These cohorts included (1) no claims for ischemic stroke or
major hemorrhage (without stroke or hemorrhage); (2) no claims for ischemic
stroke and >=1 claims for major hemorrhage (hemorrhage only); (3) >=1 claims for
ischemic stroke and no major hemorrhage claims (stroke only); and (4) >=1 claims
each for ischemic stroke and for major hemorrhage (stroke and hemorrhage). The 1
year mean postindex total all-cause healthcare costs adjusted by the Centers for
Medicare & Medicaid Services Hierarchical Condition Categories (HCC) score were
compared among the study cohorts. RESULTS: Of the 9455 eligible patients included
in this study, 3% (N = 261) of the patients had ischemic stroke claims only, 3%
(N = 276) had hemorrhage claims only, and <1% (N = 13) had both during the follow
up period. The unadjusted follow-up healthcare costs were $63,781 and $64,596 per
patient for the ischemic stroke only and the hemorrhage only cohorts,
respectively, compared with $35,474 per patient for those without hemorrhage or
stroke claims. After adjustment for HCC risk score, the mean incremental costs
for patients with stroke claims only and hemorrhage claims only, relative to
those without stroke or hemorrhage claims, were $26,776 (95% confidence interval
[CI], $20,785-$32,767; P <.001) and $26,168 (95% CI, $20,375-$31,961; P <.001),
respectively. CONCLUSION: The economic burden of managing patients with NVAF who
experience ischemic stroke and hemorrhage were similarly significant during the
first year after a diagnosis of NVAF. The burden of major bleeding complications
on patients, clinicians, and payers should not be overlooked, and these
complications should be considered in conjunction with the cost-savings
associated with ischemic stroke risk reduction in future cost-benefit evaluations
of oral anticoagulation therapy.
PMID- 25126373
TI - The health and economic effects of counterfeit drugs.
AB - BACKGROUND: Counterfeit drugs comprise an increasing percentage of the US drug
market and even a larger percentage in less developed countries. Counterfeit
drugs involve both lifesaving and lifestyle drugs. OBJECTIVE: To review the
health and economic consequences of counterfeit drugs on the US public and on the
healthcare system as a whole. METHOD: This comprehensive review of the literature
encompassed a search of MEDLINE/PubMed, Google Scholar, and ProQuest using the
keywords "counterfeit drugs," "counterfeit medicines," "fake drugs," and "fake
medicines." A search of the various FiercePharma daily newsletter series on the
healthcare market was also conducted. In addition, the US Food and Drug
Administration and the World Health Organization websites were reviewed for
additional information. DISCUSSION: The issue of counterfeit drugs has been
growing in importance in the United States, with the supply of these counterfeit
drugs coming from all over the world. Innovation is important to economic growth
and US competitiveness in the global marketplace, and intellectual property
protections provide the ability for society to prosper from innovation.
Especially important in terms of innovation in healthcare are the pharmaceutical
and biopharmaceutical industries. In addition to taking income from consumers and
drug companies, counterfeit drugs also pose health hazards to patients, including
death. The case of bevacizumab (Avastin) is presented as one recent example.
Internet pharmacies, which are often the source of counterfeit drugs, often
falsely portray themselves as Canadian, to enhance their consumer acceptance.
Adding to the problems are drug shortages, which facilitate access for
counterfeits. A long and convoluted supply chain also facilitates counterfeits.
In addition, the wholesale market involving numerous firms is a convenient target
for counterfeit drugs. Trafficking in counterfeits can be extremely profitable;
detection of counterfeits is difficult, and the penalties are modest. CONCLUSION:
Counterfeit drugs pose a public health hazard, waste consumer income, and reduce
the incentive to engage in research and development and innovation. Stronger
state licensure supervision of drug suppliers would be helpful. Technological
approaches, such as the Radio Frequency Identification devices, should also be
considered. Finally, counterfeit drugs may raise concerns among consumers about
safety and reduce patient medication adherence.
PMID- 25126374
TI - Salsalate, an old, inexpensive drug with potential new indications: a review of
the evidence from 3 recent studies.
AB - BACKGROUND: Diabetes is a well-known growing epidemic, but prediabetes is
increasing at an even greater rate. Lifestyle changes are effective tools to
prevent the progression of prediabetes to diabetes, yet many people are unable to
follow such changes. Salsalate has been suggested as a possible treatment for
diabetes as early as 1876 and as recently as in a 2013 study. OBJECTIVE: To
review the recently published evidence about the potential therapeutic benefits
of the old drug salsalate for individuals who meet the criteria of having
prediabetes. DISCUSSION: With the rising incidence of obesity and prediabetes, it
has become prudent to look for more therapeutic options. Salsalate belongs to the
salicylate drug class, which has been shown to inhibit I-kappaB kinase, thereby
inhibiting the nuclear factor-kappaB (NF-kappaB) cascade and decreasing the
production of inflammatory cytokines, as well as decreasing insulin resistance.
Recent short-term clinical trials have shown that 3 g to 4.5 g of salicylate
therapy daily has the ability to lower insulin resistance and to reduce the
levels of glucose, triglycerides, and free fatty acid concentrations through
regulation of the I-kappaB kinase beta/NF-kappaB pathway, with few if any side
effects. However, the effectiveness of salsalate as a treatment option for
prediabetes is largely unrecognized. This article summarizes the current evidence
from 3 studies of salsalate therapy in the setting of the prediabetic population
and presents the case for its use in this population. CONCLUSION: As shown in
this review, salsalate therapy at the dose of 3 g to 4.5 g daily can lower
insulin resistance and reduce the levels of glucose, triglycerides, and free
fatty acid concentrations with minimal side effects. This inexpensive medication
could be a useful option in the treatment of prediabetes. Larger clinical trials
are needed, but the data are encouraging and should lay the foundation for
further investigation and grant funding.
PMID- 25126375
TI - Pharmacy management and health economics outcomes.
AB - The following summaries highlight some of the key posters presented at the 26th
Annual Meeting of the Academy of Managed Care Pharmacy (AMCP), April 1-4, 2014,
in Tampa, FL, focusing on areas of interest for payers, employers, drug
manufacturers, providers, and other healthcare stakeholders.
PMID- 25126376
TI - Adipose-derived mesenchymal stromal/stem cells: An update on their phenotype in
vivo and in vitro.
AB - Adipose tissue is a rich, ubiquitous and easily accessible source for multipotent
stromal/stem cells and has, therefore, several advantages compared to other
sources of mesenchymal stromal/stem cells. Several studies have tried to identify
the origin of the stromal/stem cell population within adipose tissue in situ.
This is a complicated attempt because no marker has currently been described
which unambiguously identifies native adipose-derived stromal/stem cells (ASCs).
Isolated and cultured ASCs are a non-uniform preparation consisting of several
subsets of stem and precursor cells. Cultured ASCs are characterized by their
expression of a panel of markers (and the absence of others), whereas their in
vitro phenotype is dynamic. Some markers were expressed de novo during culture,
the expression of some markers is lost. For a long time, CD34 expression was
solely used to characterize haematopoietic stem and progenitor cells, but now it
has become evident that it is also a potential marker to identify an ASC
subpopulation in situ and after a short culture time. Nevertheless, long-term
cultured ASCs do not express CD34, perhaps due to the artificial environment.
This review gives an update of the recently published data on the origin and
phenotype of ASCs both in vivo and in vitro. In addition, the composition of ASCs
(or their subpopulations) seems to vary between different laboratories and
preparations. This heterogeneity of ASC preparations may result from different
reasons. One of the main problems in comparing results from different
laboratories is the lack of a standardized isolation and culture protocol for
ASCs. Since many aspects of ASCs, such as the differential potential or the
current use in clinical trials, are fully described in other recent reviews, this
review further updates the more basic research issues concerning ASCs'
subpopulations, heterogeneity and culture standardization.
PMID- 25126377
TI - Periosteum derived stem cells for regenerative medicine proposals: Boosting
current knowledge.
AB - Periosteum is a thin fibrous layer that covers most bones. It resides in a
dynamic mechanically loaded environment and provides a niche for pluripotent
cells and a source for molecular factors that modulate cell behaviour.
Elucidating periosteum regenerative potential has become a hot topic in
orthopaedics. This review discusses the state of the art of osteochondral tissue
engineering rested on periosteum derived progenitor cells (PDPCs) and suggests
upcoming research directions. Periosteal cells isolation, characterization and
migration in the site of injury, as well as their differentiation, are analysed.
Moreover, the role of cell mechanosensing and its contribution to matrix
organization, bone microarchitecture and bone stenght is examined. In this regard
the role of periostin and its upregulation under mechanical stress in order to
preserve PDPC survival and bone tissue integrity is contemplated. The review also
summarized the role of the periosteum in the field of dentistry and maxillofacial
reconstruction. The involvement of microRNAs in osteoblast differentiation and in
endogenous tissue repair is explored as well. Finally the novel concept of a
guided bone regeneration based on the use of periosteum itself as a smart
material and the realization of constructs able to mimic the extracellular matrix
features is talked out. Additionally, since periosteum can differentiate into
insulin producing cells it could be a suitable source in allogenic
transplantations. That innovative applications would take advantage from
investigations aimed to assess PDPC immune privilege.
PMID- 25126378
TI - Osteogenic potential: Comparison between bone marrow and adipose-derived
mesenchymal stem cells.
AB - Bone tissue engineering (BTE) is now a promising research issue to improve the
drawbacks from traditional bone grafting procedure such as limited donor sources
and possible complications. Stem cells are one of the major factors in BTE due to
the capability of self renewal and multi-lineage differentiation. Unlike
embryonic stem cells, which are more controversial in ethical problem, adult
mesenchymal stem cells are considered to be a more appropriate cell source for
BTE. Bone marrow mesenchymal stem cells (BMSCs) are the earliest-discovered and
well-known stem cell source using in BTE. However, the low stem cell yield
requiring long expansion time in vitro, pain and possible morbidities during bone
marrow aspiration and poor proliferation and osteogenic ability at old age impede
its' clinical application. Afterwards, a new stem cell source coming from adipose
tissue, so-called adipose-derived stem cells (ASCs), is found to be more suitable
in clinical application because of high stem cells yield from lipoaspirates,
faster cell proliferation and less discomfort and morbidities during harvesting
procedure. However, the osteogenic capacity of ASCs is now still debated because
most papers described the inferior osteogenesis of ASCs than BMSCs. A better
understanding of the osteogenic differences between ASCs and BMSCs is crucial for
future selection of cells in clinical application for BTE. In this review, we
describe the commonality and difference between BMSCs and ASCs by cell yield,
cell surface markers and multiple-differentiation potential. Then we compare the
osteogenic capacity in vitro and bone regeneration ability in vivo between BMSCs
and ASCs based on the literatures which utilized both BMSCs and ASCs
simultaneously in their articles. The outcome indicated both BMSCs and ASCs
exhibited the osteogenic ability to a certain extent both in-vitro and in-vivo.
However, most in-vitro study papers verified the inferior osteogenesis of ASCs;
conversely, in-vivo research reviews revealed more controversies in this issue.
We expect the new researchers can have a quick understanding of the progress in
this filed and design a more comprehensive research based on this review.
PMID- 25126379
TI - Mesenchymal stem cells: Potential role in corneal wound repair and
transplantation.
AB - Corneal diseases are a major cause of blindness in the world. Although great
progress has been achieved in the treatment of corneal diseases, wound healing
after severe corneal damage and immunosuppressive therapy after corneal
transplantation remain problematic. Mesenchymal stem cells (MSCs) derived from
bone marrow or other adult tissues can differentiate into various types of
mesenchymal lineages, such as osteocytes, adipocytes, and chondrocytes, both in
vivo and in vitro. These cells can further differentiate into specific cell types
under specific conditions. MSCs migrate to injury sites and promote wound healing
by secreting anti-inflammatory and growth factors. In addition, MSCs interact
with innate and acquired immune cells and modulate the immune response through
their powerful paracrine function. Over the last decade, MSCs have drawn
considerable attention because of their beneficial properties and promising
therapeutic prospective. Furthermore, MSCs have been applied to various studies
related to wound healing, autoimmune diseases, and organ transplantation. This
review discusses the potential functions of MSCs in protecting corneal tissue and
their possible mechanisms in corneal wound healing and corneal transplantation.
PMID- 25126380
TI - Sox2, a key factor in the regulation of pluripotency and neural differentiation.
AB - Sex determining region Y-box 2 (Sox2), a member of the SoxB1 transcription factor
family, is an important transcriptional regulator in pluripotent stem cells
(PSCs). Together with octamer-binding transcription factor 4 and Nanog, they co
operatively control gene expression in PSCs and maintain their pluripotency.
Furthermore, Sox2 plays an essential role in somatic cell reprogramming,
reversing the epigenetic configuration of differentiated cells back to a
pluripotent embryonic state. In addition to its role in regulation of
pluripotency, Sox2 is also a critical factor for directing the differentiation of
PSCs to neural progenitors and for maintaining the properties of neural
progenitor stem cells. Here, we review recent findings concerning the involvement
of Sox2 in pluripotency, somatic cell reprogramming and neural differentiation as
well as the molecular mechanisms underlying these roles.
PMID- 25126381
TI - Adipose-derived stem cells: Implications in tissue regeneration.
AB - Adipose-derived stem cells (ASCs) are mesenchymal stem cells (MSCs) that are
obtained from abundant adipose tissue, adherent on plastic culture flasks, can be
expanded in vitro, and have the capacity to differentiate into multiple cell
lineages. Unlike bone marrow-derived MSCs, ASCs can be obtained from abundant
adipose tissue by a minimally invasive procedure, which results in a high number
of cells. Therefore, ASCs are promising for regenerating tissues and organs
damaged by injury and diseases. This article reviews the implications of ASCs in
tissue regeneration.
PMID- 25126383
TI - Mesenchymal stem cells as a potent cell source for articular cartilage
regeneration.
AB - Since articular cartilage possesses only a weak capacity for repair, its
regeneration potential is considered one of the most important challenges for
orthopedic surgeons. The treatment options, such as marrow stimulation
techniques, fail to induce a repair tissue with the same functional and
mechanical properties of native hyaline cartilage. Osteochondral transplantation
is considered an effective treatment option but is associated with some
disadvantages, including donor-site morbidity, tissue supply limitation,
unsuitable mechanical properties and thickness of the obtained tissue. Although
autologous chondrocyte implantation results in reasonable repair, it requires a
two-step surgical procedure. Moreover, chondrocytes expanded in culture gradually
undergo dedifferentiation, so lose morphological features and specialized
functions. In the search for alternative cells, scientists have found mesenchymal
stem cells (MSCs) to be an appropriate cellular material for articular cartilage
repair. These cells were originally isolated from bone marrow samples and further
investigations have revealed the presence of the cells in many other tissues.
Furthermore, chondrogenic differentiation is an inherent property of MSCs noticed
at the time of the cell discovery. MSCs are known to exhibit homing potential to
the damaged site at which they differentiate into the tissue cells or secrete a
wide spectrum of bioactive factors with regenerative properties. Moreover, these
cells possess a considerable immunomodulatory potential that make them the
general donor for therapeutic applications. All of these topics will be discussed
in this review.
PMID- 25126385
TI - Umbilical cord fibroblasts: Could they be considered as mesenchymal stem cells?
AB - In cell therapy protocols, many tissues were proposed as a source of mesenchymal
stem cells (MSC) isolation. So far, bone marrow (BM) has been presented as the
main source of MSC despite the invasive isolation procedure related to this
source. During the last years, the umbilical cord (UC) matrix was cited in
different studies as a reliable source from which long term ex vivo proliferating
fibroblasts were isolated but with contradictory data about their
immunophenotype, gene expression profile, and differentiation potential. Hence,
an interesting question emerged: Are cells isolated from cord matrix (UC-MSC)
different from other MSCs? In this review, we will summarize different studies
that isolated and characterized UC-MSC. Considering BM-MSC as gold standard, we
will discuss if UC-MSC fulfill different criteria that define MSC, and what
remain to be done in this issue.
PMID- 25126384
TI - Endothelial progenitor cells in cardiovascular diseases.
AB - Endothelial dysfunction has been associated with the development of
atherosclerosis and cardiovascular diseases. Adult endothelial progenitor cells
(EPCs) are derived from hematopoietic stem cells and are capable of forming new
blood vessels through a process of vasculogenesis. There are studies which report
correlations between circulating EPCs and cardiovascular risk factors. There are
also studies on how pharmacotherapies may influence levels of circulating EPCs.
In this review, we discuss the potential role of endothelial progenitor cells as
both diagnostic and prognostic biomarkers. In addition, we look at the
interaction between cardiovascular pharmacotherapies and endothelial progenitor
cells. We also discuss how EPCs can be used directly and indirectly as a
therapeutic agent. Finally, we evaluate the challenges facing EPC research and
how these may be overcome.
PMID- 25126386
TI - The 2-Methoxy Group Orientation Regulates the Redox Potential Difference between
the Primary (QA) and Secondary (QB) Quinones of Type II Bacterial Photosynthetic
Reaction Centers.
AB - Recent studies have shown that only quinones with a 2-methoxy group can act
simultaneously as the primary (QA) and secondary (QB) electron acceptors in
photosynthetic reaction centers from purple bacteria such as Rb. sphaeroides. 13C
HYSCORE measurements of the 2-methoxy group in the semiquinone states, SQA and
SQB, were compared with DFT calculations of the 13C hyperfine couplings as a
function of the 2-methoxy dihedral angle. X-ray structure comparisons support 2
methoxy dihedral angle assignments corresponding to a redox potential gap
(DeltaEm) between QA and QB of 175-193 mV. A model having a methyl group
substituted for the 2-methoxy group exhibits no electron affinity difference.
This is consistent with the failure of a 2-methyl ubiquinone analogue to function
as QB in mutant reaction centers with a DeltaEm of ~160-195 mV. The conclusion
reached is that the 2-methoxy group is the principal determinant of electron
transfer from QA to QB in type II photosynthetic reaction centers with ubiquinone
serving as both acceptor quinones.
PMID- 25126382
TI - Multiple myeloma mesenchymal stromal cells: Contribution to myeloma bone disease
and therapeutics.
AB - Multiple myeloma is a hematological malignancy in which clonal plasma cells
proliferate and accumulate within the bone marrow. The presence of osteolytic
lesions due to increased osteoclast (OC) activity and suppressed osteoblast (OB)
function is characteristic of the disease. The bone marrow mesenchymal stromal
cells (MSCs) play a critical role in multiple myeloma pathophysiology, greatly
promoting the growth, survival, drug resistance and migration of myeloma cells.
Here, we specifically discuss on the relative contribution of MSCs to the
pathophysiology of osteolytic lesions in light of the current knowledge of the
biology of myeloma bone disease (MBD), together with the reported genomic,
functional and gene expression differences between MSCs derived from myeloma
patients (pMSCs) and their healthy counterparts (dMSCs). Being MSCs the
progenitors of OBs, pMSCs primarily contribute to the pathogenesis of MBD because
of their reduced osteogenic potential consequence of multiple OB inhibitory
factors and direct interactions with myeloma cells in the bone marrow.
Importantly, pMSCs also readily contribute to MBD by promoting OC formation and
activity at various levels (i.e., increasing RANKL to OPG expression, augmenting
secretion of activin A, uncoupling ephrinB2-EphB4 signaling, and through
augmented production of Wnt5a), thus further contributing to OB/OC uncoupling in
osteolytic lesions. In this review, we also look over main signaling pathways
involved in the osteogenic differentiation of MSCs and/or OB activity,
highlighting amenable therapeutic targets; in parallel, the reported activity of
bone-anabolic agents (at preclinical or clinical stage) targeting those signaling
pathways is commented.
PMID- 25126387
TI - FTIR Spectroscopy Revealing Light-Dependent Refolding of the Conserved Tongue
Region of Bacteriophytochrome.
AB - Bacteriophytochromes (BphPs) constitute a class of photosensory proteins that
toggle between Pr and Pfr functional states through absorption of red and far-red
light. The photosensory core of BphPs is composed of PAS, GAF, and PHY domains.
Here, we apply FTIR spectroscopy to investigate changes in the secondary
structure of Rhodopseudomonas palustris BphP2 (RpBphP2) upon Pr to Pfr
photoconversion. Our results indicate conversion from a beta-sheet to an alpha
helical element in the so-called tongue region of the PHY domain, consistent with
recent X-ray structures of Deinococcus radiodurans DrBphP in dark and light
states (Takala H.; et al. Nature2014, 5, 245-248). A conserved Asp in the GAF
domain that noncovalently connects with the PHY domain and a conserved Pro in the
tongue region of the PHY domain are essential for the beta-sheet-to-alpha-helix
conversion.
PMID- 25126388
TI - Biological Targeting of Plasmonic Nanoparticles Improves Cellular Imaging via the
Enhanced Scattering in the Aggregates Formed.
AB - Gold nanoparticles (AuNPs) demonstrate great promise in biomedical applications
due to their plasmonically enhanced imaging properties. When in close proximity,
AuNPs plasmonic fields couple together, increasing their scattering cross-section
due to the formation of hot spots, improving their imaging utility. In the
present study, we modified the AuNPs surface with different peptides to target
the nucleus and/or the cell as a whole, resulting in similar cellular uptake but
different scattering intensities. Nuclear-targeted AuNPs showed the greatest
scattering due to the formation of denser nanoparticle clusters (i.e., increased
localization). We also obtained a dynamic profile of AuNP localization in living
cells, indicating that nuclear localization is directly related to the number of
nuclear-targeting peptides on the AuNP surface. Increased localization led to
increased plasmonic field coupling, resulting in significantly higher scattering
intensity. Thus, biochemical targeting of plasmonic nanoparticles to subcellular
components is expected to lead to more resolved imaging of cellular processes.
PMID- 25126389
TI - Pancreatic steatosis: Is it related to either obesity or diabetes mellitus?
AB - The accumulation of fat in the pancreatic gland has been referred to using
various synonyms, such as pancreatic lipomatosis, fatty replacement, fatty
infiltration, fatty pancreas, lipomatous pseudohypertrophy, non-alcoholic fatty
pancreatic disease and pancreatic steatosis We believe that pancreatic steatosis
is the best description of fat accumulation in the pancreatic gland without fat
replacement, and this term also describes the possibility that the fat
accumulation is a reversible process. A review of the existing literature was
carried out, and it was found that there was notable evidence from both the
pathological and the imaging point of view that pancreatic steatosis is an
increasing problem due to the increasing incidence of obesity. The conclusion was
that pancreatic steatosis was easily detectable using modern imaging techniques,
such as ultrasonography, endoscopic ultrasonography, computed tomography and
magnetic resonance imaging. Pancreatic steatosis was not due to the presence of
diabetes mellitus but was highly associated with the metabolic syndrome. The
possible presence of steatopancreatitis should be better evaluated, especially
regarding the inflammatory cascade, and additional studies are needed which are
capable of assessing whether non-alcoholic steatopancreatitis really exists as
does non-alcoholic steatohepatitis. Finally, the presence of exocrine pancreatic
function should be extensively evaluated in patients with pancreatic steatosis.
PMID- 25126390
TI - Benefits of healthy adipose tissue in the treatment of diabetes.
AB - The major malfunction in diabetes mellitus is severe perturbation of glucose
homeostasis caused by deficiency of insulin. Insulin deficiency is either
absolute due to destruction or failure of pancreatic beta cells, or relative due
to decreased sensitivity of peripheral tissues to insulin. The primary lesion
being related to insulin, treatments for diabetes focus on insulin replacement
and/or increasing sensitivity to insulin. These therapies have their own
limitations and complications, some of which can be life-threatening. For
example, exogenous insulin administration can lead to fatal hypoglycemic
episodes; islet/pancreas transplantation requires life-long immunosuppressive
therapy; and anti-diabetic drugs have dangerous side effects including edema,
heart failure and lactic acidosis. Thus the need remains for better safer long
term treatments for diabetes. The ultimate goal in treating diabetes is to re
establish glucose homeostasis, preferably through endogenously generated
hormones. Recent studies increasingly show that extra-pancreatic hormones,
particularly those arising from adipose tissue, can compensate for insulin, or
entirely replace the function of insulin under appropriate circumstances. Adipose
tissue is a versatile endocrine organ that secretes a variety of hormones with
far-reaching effects on overall metabolism. While unhealthy adipose tissue can
exacerbate diabetes through limiting circulation and secreting of pro
inflammatory cytokines, healthy uninflamed adipose tissue secretes beneficial
adipokines with hypoglycemic and anti-inflammatory properties, which can
complement and/or compensate for the function of insulin. Administration of
specific adipokines is known to alleviate both type 1 and 2 diabetes, and leptin
mono-therapy is reported to reverse type 1 diabetes independent of insulin.
Although specific adipokines may correct diabetes, administration of individual
adipokines still carries risks similar to those of insulin monotherapy. Thus a
better approach is to achieve glucose homeostasis with endogenously-generated
adipokines through transplantation or regeneration of healthy adipose tissue. Our
recent studies on mouse models show that type 1 diabetes can be reversed without
insulin through subcutaneous transplantation of embryonic brown adipose tissue,
which leads to replenishment of recipients' white adipose tissue; increase of a
number of beneficial adipokines; and fast and long-lasting euglycemia. Insulin
independent glucose homeostasis is established through a combination of
endogenously generated hormones arising from the transplant and/or newly
replenished white adipose tissue. Transplantation of healthy white adipose tissue
is reported to alleviate type 2 diabetes in rodent models on several occasions,
and increasing the content of endogenous brown adipose tissue is known to combat
obesity and type 2 diabetes in both humans and animal models. While the
underlying mechanisms are not fully documented, the beneficial effects of healthy
adipose tissue in improving metabolism are increasingly reported, and are worthy
of attention as a powerful tool in combating metabolic disease.
PMID- 25126391
TI - Inflammation in diabetic kidney disease.
AB - Diabetes mellitus entails significant health problems worldwide. The pathogenesis
of diabetes is multifactorial, resulting from interactions of both genetic and
environmental factors that trigger a complex network of pathophysiological
events, with metabolic and hemodynamic alterations. In this context, inflammation
has emerged as a key pathophysiology mechanism. New pathogenic pathways will
provide targets for prevention or future treatments. This review will focus on
the implications of inflammation in diabetes mellitus, with special attention to
inflammatory cytokines.
PMID- 25126393
TI - Structured SMBG in early management of T2DM: Contributions from the St Carlos
study.
AB - Diabetes mellitus type 2 (T2DM) is a global pandemic that will affect 300 million
people in the next decade. It has been shown that early and aggressive treatment
of T2DM from the onset decreases complications, and the patient's active role is
necessary to achieve better glycemic control. In order to achieve glycemic
control targets, an active attitude in patients is needed, and self-monitoring of
blood glucose (SMBG) plays a significant role. Nowadays, SMBG has become an
important component of modern therapy for diabetes mellitus, and is even more
useful if it is performed in a structured way. SMBG aids physicians and patients
to achieve a specific level of glycemic control and to prevent hypoglycemia. In
addition, SMBG empowers patients to achieve nutritional and physical activity
goals, and helps physicians to optimize the different hypoglycemic therapies as
demonstrated in the St Carlos study. This article describes the different ways of
using this educational and therapeutic tool from the medical point of view as
well as from the patient's perspective.
PMID- 25126394
TI - Effects of exercise training on mitochondrial function in patients with type 2
diabetes.
AB - Type 2 diabetes is characterized by a decreased ability of insulin to facilitate
glucose uptake into insulin sensitive tissue, i.e., skeletal muscle. The
mechanism behind this is at the moment unresolved. It has been suggested that
increased amount of lipids inside the skeletal muscle (intramuscular
triglyceride, diacylglycerol and ceramides) will impair insulin action in
skeletal muscle, but data are not consistent in the human literature. It has also
been hypothesized that the impaired insulin sensitivity is due to a dysfunction
in the mitochondria resulting in an impaired ability to oxidize lipids, but the
majority of the literature is not supporting this hypothesis. Recently it has
been suggested that the production of reactive oxygen species play an essential
role in skeletal muscle insulin sensitivity. It is well accepted that physical
activity (endurance, strength and high intensity training) improves insulin
sensitivity in healthy humans and in patients with type 2 diabetes. Whether
patients with type 2 diabetes have the same beneficial effects (same improvement)
as control subjects, when it comes to regular physical activity in regard to
mitochondrial function, is not established in the literature. This review will
focus only on the effect of physical activity on skeletal muscle (mitochondrial
function) in patients with type 2 diabetes.
PMID- 25126396
TI - Distinct clinical and laboratory characteristics of latent autoimmune diabetes in
adults in relation to type 1 and type 2 diabetes mellitus.
AB - Ever since its first appearance among the multiple forms of diabetes, latent
autoimmune diabetes in adults (LADA), has been the focus of endless discussions
concerning mainly its existence as a special type of diabetes. In this mini
review, through browsing important peer-reviewed publications, (original articles
and reviews), we will attempt to refresh our knowledge regarding LADA hoping to
enhance our understanding of this controversial diabetes entity. A unique
combination of immunological, clinical and metabolic characteristics has been
identified in this group of patients, namely persistent islet cell antibodies,
high frequency of thyroid and gastric autoimmunity, DR3 and DR4 human leukocyte
antigen haplotypes, progressive loss of beta cells, adult disease onset, normal
weight, defective glycaemic control, and without tendency to ketoacidosis.
Although anthropomorphic measurements are useful as a first line screening, the
detection of C-peptide levels and the presence of glutamic acid decarboxylase
(GAD) autoantibodies is undoubtedly the sine qua non condition for a confirmatory
LADA diagnosis. In point of fact, GAD autoantibodies are far from being solely a
biomarker and the specific role of these autoantibodies in disease pathogenesis
is still to be thoroughly studied. Nevertheless, the lack of diagnostic criteria
and guidelines still puzzle the physicians, who struggle between early diagnosis
and correct timing for insulin treatment.
PMID- 25126395
TI - Genetic polymorphisms of cytokine genes in type 2 diabetes mellitus.
AB - Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia,
dyslipidemia, stroke and several other complications. Various groups all over the
world are relentlessly working out the possible role of a vast number of genes
associated with type 2 diabetes (T2DM). Inflammation is an important outcome of
any kind of imbalance in the body and is therefore an indicator of several
diseases, including T2DM. Various ethnic populations around the world show
different levels of variations in single nucleotide polymorphisms (SNPs). The
present review was undertaken to explore the association of cytokine gene
polymorphisms with T2DM in populations of different ethnicities. This will lead
to the understanding of the role of cytokine genes in T2DM risk and development.
Association studies of genotypes of SNPs present in cytokine genes will help to
identify risk haplotype(s) for disease susceptibility by developing prognostic
markers and alter treatment strategies for T2DM and related complications. This
will enable individuals at risk to take prior precautionary measures and avoid or
delay the onset of the disease. Future challenges will be to understand the
genotypic interactions between SNPs in one cytokine gene or several genes at
different loci and study their association with T2DM.
PMID- 25126392
TI - Type 2 diabetes and cardiovascular disease: Have all risk factors the same
strength?
AB - Diabetes mellitus is a chronic condition that occurs when the body cannot produce
enough or effectively use of insulin. Compared with individuals without diabetes,
patients with type 2 diabetes mellitus have a considerably higher risk of
cardiovascular morbidity and mortality, and are disproportionately affected by
cardiovascular disease. Most of this excess risk is it associated with an
augmented prevalence of well-known risk factors such as hypertension,
dyslipidaemia and obesity in these patients. However the improved cardiovascular
disease in type 2 diabetes mellitus patients can not be attributed solely to the
higher prevalence of traditional risk factors. Therefore other non-traditional
risk factors may be important in people with type 2 diabetes mellitus.
Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a
complex combination of various traditional and non-traditional risk factors that
have an important role to play in the beginning and the evolution of
atherosclerosis over its long natural history from endothelial function to
clinical events. Many of these risk factors could be common history for both
diabetes mellitus and cardiovascular disease, reinforcing the postulate that both
disorders come independently from "common soil". The objective of this review is
to highlight the weight of traditional and non-traditional risk factors for
cardiovascular disease in the setting of type 2 diabetes mellitus and discuss
their position in the pathogenesis of the excess cardiovascular disease mortality
and morbidity in these patients.
PMID- 25126398
TI - Domino effect of hypomagnesemia on the innate immunity of Crohn's disease
patients.
AB - Digestive diseases play major role in development and complications of other
disorders including diabetes. For example, Crohn's disease (CD) is an
inflammatory bowel disease associated with Mycobacterium avium subspecies
paratuberculosis. The inflammation is a complex process that involves the
activity of both innate and adaptive immune responses. CD lesions are primarily
due to T cell response, however; innate immune response has a significant role in
initiating its pathogenesis. Toll-like receptors and NOD-like receptors promote
the activity of nuclear factor (NF)-kappaB pathway for cytokines production. This
results in the production of high levels of tumor necrosis factor-alpha,
interleukin (IL)-1beta and IL-6. Moreover, intestinal inflammation of CD is
related to increased activity of NMDA receptors and the release of substance P.
Imbalanced magnesium homeostasis in CD is a frequent finding in CD, Diabetes and
others. The loss of such a major mineral affects many physiological processes in
the body including its role as an immunomodulator. This review aims to (1)
describe the significance of hypomagnesemia in the release of pro-inflammatory
mediators in CD; (2) demonstrate effects of magnesium on pathways like NF-kappaB;
(3) address the role of hypomagnesemia in the activity of CD; and (4) examine
possible future research to establish a standard magnesium supplementation
strategy; helping patients with CD or other disorders to maintain a sustained
remission.
PMID- 25126399
TI - Novel treatment approaches in hypertensive type 2 diabetic patients.
AB - Type 2 diabetes mellitus (T2DM) and hypertension represent two common conditions
worldwide. Their frequent association with cardiovascular diseases makes
management of hypertensive patients with T2DM an important clinical priority.
Carvedilol and renal denervation are two promising choices to reduce plasma
glucose levels and blood pressure in hypertensive patients with T2DM to reduce
future complications and improve clinical outcomes and prognosis.
Pathophysiological mechanisms of both options are under investigation, but one of
the most accepted is an attenuation in sympathetic nervous system activity which
lowers blood pressure and improves insulin sensitivity. Choice of these
therapeutic approaches should be individualized based on specific characteristics
of each patient. Further investigations are needed to determine when to consider
their use in clinical practice.
PMID- 25126397
TI - SH2B1 regulation of energy balance, body weight, and glucose metabolism.
AB - The Src homology 2B (SH2B) family members (SH2B1, SH2B2 and SH2B3) are adaptor
signaling proteins containing characteristic SH2 and PH domains. SH2B1 (also
called SH2-B and PSM) and SH2B2 (also called APS) are able to form homo- or
hetero-dimers via their N-terminal dimerization domains. Their C-terminal SH2
domains bind to tyrosyl phosphorylated proteins, including Janus kinase 2 (JAK2),
TrkA, insulin receptors, insulin-like growth factor-1 receptors, insulin receptor
substrate-1 (IRS1), and IRS2. SH2B1 enhances leptin signaling by both stimulating
JAK2 activity and assembling a JAK2/IRS1/2 signaling complex. SH2B1 promotes
insulin signaling by both enhancing insulin receptor catalytic activity and
protecting against dephosphorylation of IRS proteins. Accordingly, genetic
deletion of SH2B1 results in severe leptin resistance, insulin resistance,
hyperphagia, obesity, and type 2 diabetes in mice. Neuron-specific overexpression
of SH2B1beta transgenes protects against diet-induced obesity and insulin
resistance. SH2B1 in pancreatic beta cells promotes beta cell expansion and
insulin secretion to counteract insulin resistance in obesity. Moreover, numerous
SH2B1 mutations are genetically linked to leptin resistance, insulin resistance,
obesity, and type 2 diabetes in humans. Unlike SH2B1, SH2B2 and SH2B3 are not
required for the maintenance of normal energy and glucose homeostasis. The
metabolic function of the SH2B family is conserved from insects to humans.
PMID- 25126400
TI - Choice of wound care in diabetic foot ulcer: A practical approach.
AB - Diabetic foot ulcers are the consequence of multiple factors including peripheral
neuropathy, decreased blood supply, high plantar pressures, etc., and pose a
significant risk for morbidity, limb loss and mortality. The critical aspects of
the wound healing mechanism and host physiological status in patients with
diabetes necessitate the selection of an appropriate treatment strategy based on
the complexity and type of wound. In addition to systemic antibiotics and
surgical intervention, wound care is considered to be an important component of
diabetic foot ulcer management. This article will focus on the use of different
wound care materials in diabetic foot. From a clinical perspective, it is
important to decide on the wound care material depending on the type and grade of
the ulcer. This article will also provide clinicians with a simple approach to
the choice of wound care materials in diabetic foot ulcer.
PMID- 25126401
TI - Study of factors influencing susceptibility and age at onset of type 1 diabetes:
A review of data from Continental Italy and Sardinia.
AB - AIM: To investigate the role of protein tyrosin phosphatase 22 (PTPN22), maternal
age at conception and sex on susceptibility and age at onset of type 1 diabetes
(T1D) in Continental Italy and Sardinian populations. METHODS: Three hundred
seventy six subjects admitted consecutively to the hospital for T1D and 1032
healthy subjects as controls were studied in Continental Italy and 284 subjects
admitted consecutively to the hospital for T1D and 5460 healthy newborns were
studied in Sardinia. PTPN22 genotype was determined by DNA analysis. Maternal age
at conception and age at onset of disease were obtained from clinical records.
chi(2) test of independence, student t test for differences between means and
odds ratio analysis were carried out by SPSS programs. Three way contingency
table analysis was carried out according to Sokal and Rohlf. RESULTS: The pattern
of association between PTPN22 and T1D is similar in Continental Italy and
Sardinia: the proportion of *T allele carriers is 13.6% in T1D vs 6.7% in
controls in Continental Italy while in Sardinia is 7.3% in T1D vs 4.4% in
controls. The association between T1D and maternal age at conception is much
stronger in Sardinia than in Italy: the proportion of newborn from mother aging
more than 32 years is 89.3% in T1D vs 32.7% in consecutive newborn in Sardinia (P
< 10(-6)) while in Continental Italy is 32.2% in T1D vs 19.1% in consecutive
newborns (P = 0.005). This points to an important role of ethnicity. A slight
prevalence of T1D males on T1D females is observed both in Continental Italy and
Sardinia. PTPN22 genotype does not exert significant effect on the age at onset
neither in Continental Italy nor and Sardinia. Maternal age does not influence
significantly age at onset in Italy (8.2 years in T1D infants from mothers aging
32 years or less vs 7.89 years in T1D infants from mothers aging more than 32
years: P = 0.824) while in Sardinia a border line effect is observed (5.75 years
in T1D infants from mothers aging 32 years or less vs 7.54 years in T1D infants
from mothers aging more than 32 years: P = 0.062). No effect of sex on age at
onset is observed in Continental Italy while in Sardinia female show a lower age
at onset of T1D as compared to males (8.07 years in males vs 6.3 years in
females: P = 0.002). CONCLUSION: The present data confirm the importance of
ethnicity on susceptibility and on the age at onset of T1D.
PMID- 25126402
TI - Conventional insulin vs insulin infusion therapy in acute coronary syndrome
diabetic patients.
AB - AIM: To evaluate the impact on glucose variability (GLUCV) of an nurse
implemented insulin infusion protocol when compared with a conventional insulin
treatment during the day-to-day clinical activity. METHODS: We enrolled 44 type 2
diabetic patients (n = 32 males; n = 12 females) with acute coronary syndrome
(ACS) and randomy assigned to standard a subcutaneous insulin treatment (n = 23)
or a nurse-implemented continuous intravenous insulin infusion protocol (n = 21).
We utilized some parameters of GLUCV representing well-known surrogate markers of
prognosis, i.e., glucose standard deviation (SD), the mean daily delta glucose
(mean of daily difference between maximum and minimum glucose), and the
coefficient of variation (CV) of glucose, expressed as percent glucose
(SD)/glucose (mean). RESULTS: At the admission, first fasting blood glucose,
pharmacological treatments (insulin and/or anti-diabetic drugs) prior to entering
the study and basal glycated hemoglobin (HbA1c) were observed in the two groups
treated with subcutaneous or intravenous insulin infusion, respectively. When
compared with patients submitted to standard therapy, insulin-infused patients
showed both increased first 24-h (median 6.9 mmol/L vs 5.7 mmol/L P < 0.045) and
overall hospitalization delta glucose (median 10.9 mmol/L vs 9.3 mmol/L, P <
0.028), with a tendency to a significant increase in first 24-h glycaemic CV
(23.1% vs 19.6%, P < 0.053). Severe hypoglycaemia was rare (14.3%), and it was
observed only in 3 patients receiving insulin infusion therapy. HbA1c values
measured during hospitalization and 3 mo after discharge did not differ in the
two groups of treatment. CONCLUSION: Our pilot data suggest that no real benefit
in terms of GLUCV is observed when routinely managing blood glucose by insulin
infusion therapy in type 2 diabetic ACS hospitalized patients in respect to
conventional insulin treatment.
PMID- 25126403
TI - Fifteen-year follow-up of quality of life in type 1 diabetes mellitus.
AB - AIM: To evaluate metabolic control and health-related quality of life (HRQOL) in
a type 1 diabetes mellitus (T1DM) population. METHODS: As part of a prospective
cohort study, 283 T1DM patients treated with various insulin treatment modalities
including multiple daily injections (MDI) and continuous subcutaneous insulin
infusion (CSII) were examined annually. HRQOL was measured using the SF-36 and
EuroQol questionnaires. Data regarding HRQOL, glycaemic and metabolic control
from baseline and follow-up measures in 2002 and 2010 were analysed. Linear mixed
models were used to calculate estimated values and differences between the three
moments in time and the three treatment modalities. RESULTS: Significant changes
[mean Delta (95%CI)] in body mass index [2.4 kg/m(2) (1.0, 3.8)], systolic blood
pressure [-6.4 mmHg (-11.4, -1.3)] and EuroQol-VAS [-7.3 (-11.4, -3.3)] were
observed over time. In 2010, 168 patients were lost to follow-up. Regarding mode
of therapy, 52 patients remained on MDI, 28 remained on CSII, and 33 patients
switched from MDI to CSII during follow-up. Among patients on MDI, HRQOL
decreased significantly over time: mental component summary [-9.8 (-16.3, -3.2)],
physical component summary [-8.6 (-15.3, -1.8)] and EuroQol-VAS [-8.1 (-14.0,
2.3)], P < 0.05 for all. For patients using CSII, the EuroQol-VAS decreased [-9.6
(-17.5, -1.7)]. None of the changes over time in HRQOL differed significantly
with the changes over time within the other treatment groups. CONCLUSION: No
differences with respect to metabolic and HRQOL parameters between the various
insulin treatment modalities were observed after 15 years of follow-up in T1DM
patients.
PMID- 25126404
TI - The Early Determinants of Adult Health Study.
AB - This issue of the Journal features collaborative follow-up studies of two unique
pregnancy cohorts recruited during 1959-1966 in the United States. Here we
introduce the Early Determinants of Adult Health (EDAH) study. EDAH was designed
to compare health outcomes in midlife (age 40s) for same-sex siblings discordant
on birthweight for gestational age. A sufficient sample of discordant siblings
could only be obtained by combining these two cohorts in a single follow-up
study. All of the subsequent six papers are either based upon the EDAH sample or
are related to it in various ways. For example, three papers report results from
studies that significantly extended the 'core' EDAH sample to address specific
questions. We first present the overall design of and rationale for the EDAH
study. Then we offer a synopsis of past work with the two cohorts to provide a
context for both EDAH and the related studies. Next, we describe the recruitment
and assessment procedures for the core EDAH sample. This includes the process of
sampling and recruitment of potential participants; a comparison of those who
were assessed and not assessed based on archived data; the methods used in the
adult follow-up assessment; and the characteristics at follow-up of those who
were assessed. We provide online supplementary tables with much further detail.
Finally, we note further work in progress on EDAH and related studies, and draw
attention to the broader implications of this endeavor.
PMID- 25126405
TI - Serum microRNA profiles in children with autism.
AB - BACKGROUND: As regulators of gene expression, microRNAs (miRNAs) play a key role
in the transcriptional networks of the developing human brain. Circulating miRNAs
in the serum and plasma are remarkably stable and are suggested to have promise
as noninvasive biomarkers for neurological and neurodevelopmental disorders. We
examined the serum expression profiles of neurologically relevant miRNAs in
autism spectrum disorder (ASD), a complex neurodevelopmental disorder
characterized by multiple deficits in communication, social interaction and
behavior. METHODS: Total RNA, including miRNA, was extracted from the serum
samples of 55 individuals with ASD and 55 age- and sex-matched control subjects,
and the mature miRNAs were selectively converted into cDNA. Initially, the
expression of 125 mature miRNAs was compared between pooled control and ASD
samples. The differential expression of 14 miRNAs was further validated by SYBR
Green quantitative PCR of individual samples. Receiver-operating characteristic
(ROC) analysis was used to evaluate the sensitivity and specificity of miRNAs.
The target genes and pathways of miRNAs were predicted using DIANA mirPath
software. RESULTS: Thirteen miRNAs were differentially expressed in ASD
individuals compared to the controls. MiR-151a-3p, miR-181b-5p, miR-320a, miR
328, miR-433, miR-489, miR-572, and miR-663a were downregulated, while miR-101
3p, miR-106b-5p, miR-130a-3p, miR-195-5p, and miR-19b-3p were upregulated. Five
miRNAs showed good predictive power for distinguishing individuals with ASD. The
target genes of these miRNAs were enriched in several crucial neurological
pathways. CONCLUSIONS: This is the first study of serum miRNAs in ASD
individuals. The results suggest that a set of serum miRNAs might serve as a
possible noninvasive biomarker for ASD.
PMID- 25126406
TI - Proteomic analysis of post mortem brain tissue from autism patients: evidence for
opposite changes in prefrontal cortex and cerebellum in synaptic connectivity
related proteins.
AB - BACKGROUND: Autism is a neurodevelopmental disorder characterized by impaired
language, communication and social skills. Although genetic studies have been
carried out in this field, none of the genes identified have led to an
explanation of the underlying causes. Here, we have investigated molecular
alterations by proteomic profiling of post mortem brain samples from autism
patients and controls. The analysis focussed on prefrontal cortex and cerebellum
as previous studies have found that these two brain regions are structurally and
functionally connected, and they have been implicated in autism. METHODS: Post
mortem prefrontal cortex and cerebellum samples from autism patients and matched
controls were analysed using selected reaction monitoring mass spectrometry (SRM
MS). The main objective was to identify significantly altered proteins and
biological pathways and to compare these across these two brain regions. RESULTS:
Targeted SRM-MS resulted in identification of altered levels of proteins related
to myelination, synaptic vesicle regulation and energy metabolism. This showed
decreased levels of the immature astrocyte marker vimentin in both brain regions,
suggesting a decrease in astrocyte precursor cells. Also, decreased levels of
proteins associated with myelination and increased synaptic and energy-related
proteins were found in the prefrontal cortex, indicative of increased synaptic
connectivity. Finally, opposite directional changes were found for myelination
and synaptic proteins in the cerebellum. CONCLUSION: These findings suggest
altered structural and/or functional connectivity in the prefrontal cortex and
cerebellum in autism patients, as shown by opposite effects on proteins involved
in myelination and synaptic function. Further investigation of these findings
could help to increase our understanding of the mechanisms underlying autism
relating to brain connectivity, with the ultimate aim of facilitating novel
therapeutic approaches.
PMID- 25126407
TI - Level of A1C control and its predictors among Lebanese type 2 diabetic patients.
AB - AIM: Lebanon is among the top 10 countries with the highest prevalence of
diabetes in the Middle East region with estimates reaching as high as 16.6% in
adults aged 20-79 years. The objective of this study was to assess the level of
A1C control among a cohort of type 2 diabetic patients and factors associated
with uncontrolled A1C. METHODS: We carried out a retrospective observational
study among type 2 diabetes mellitus patients attending an outpatient
endocrinologist's clinic between June 2008 and July 2012 in Beirut, Lebanon. Two
groups were compared, based on their diabetic control (A1C < 7% and A1C >= 7%).
RESULTS: A total of 551 patients were included in this study, where 31.8%
attained A1C control. Crude analyses showed that some factors were significantly
associated with uncontrolled A1C, and these were long-standing diabetes, diabetes
related complications, uncontrolled blood pressure, lipid profile, as well as the
use of metformin, sulfonylurea, or insulin. When multivariate analysis was
carried out, the chances of having uncontrolled A1C were significantly higher
among patients who developed neuropathy (odds ratio [OR] 2.08, 95% confidence
interval [CI] 1.11-3.90), had uncontrolled triglycerides (OR 1.98, 95% CI 1.33
2.94), used insulin (OR 4.52, 95% CI 2.32-8.83), and sulfonylureas (OR 2.88, 95%
CI 1.88-4.40). CONCLUSION: Uncontrolled diabetes is more likely to exist in
patients with neuropathy, uncontrolled triglycerides and those using insulin or
sulfonylurea. Further research is needed to confirm the findings.
PMID- 25126408
TI - Renal effects of dapagliflozin in patients with type 2 diabetes.
AB - Diabetes mellitus was originally conceived as a renal disorder. In the last
decade, however, there has been renewed interest in role of the kidney in the
development and maintenance of high glucose levels. This has led to the
development of novel agents to inhibit sodium glucose transporter-2 (SGLT2) as a
means to better control glucose levels and at the same time augment calorie
wasting and lower insulin, blood pressure and uric acid levels. Such actions,
indirectly, may also have benefits for the prevention of diabetic complications
including renal disease. However, there are also data to support the potential
for direct renoprotective actions arising from inhibition of SGLT2, including
actions to attenuate diabetes-associated hyperfiltration and tubular hypertrophy,
as well as reduce the tubular toxicity of glucose. Some studies have demonstrated
significant reductions in albumin excretion in various experimental models,
independent of its effects on blood pressure or glucose control. Although
promising, such actions remain to be established by comprehensive clinical trials
with a renal focus, many of which are currently in progress. This article reviews
the clinical and experimental data pertaining to the renal effects of SGLT2
inhibition with a particular focus on dapaglifozin.
PMID- 25126409
TI - Comprehensive analysis of published studies involving systemic treatment for
chondrosarcoma of bone between 2000 and 2013.
AB - BACKGROUND: The majority of patients with chondrosarcoma of bone have an
excellent overall survival after local therapy. However, in case of unresectable
locally advanced or metastatic disease the outcome is poor and limited treatment
options exist. Therefore we conducted a survey of clinical phase I or II trials
and retrospective studies that described systemic therapy for chondrosarcoma
patients. MATERIALS AND METHODS: Using PubMed, clinicaltrials.gov, the Cochrane
controlled trial register and American Society of Clinical Oncology (ASCO)
abstracts a literature survey was conducted. From the identified items, data were
collected by a systematic analysis. We limited our search to semi-recent studies
published between 2000 and 2013 to include modern drugs, imaging techniques and
disease evaluations. RESULTS: A total of 31 studies were found which met the
criteria: 9 phase I trials, 11 phase II and 8 retrospective studies. In these
studies 855 chondrosarcoma patients were reported. The tested drugs were mostly
non-cytotoxic, either alone or in combination with another non-cytotoxic agent or
chemotherapy. Currently two phase I trials, one phase IB/II trial and three phase
II trials are enrolling chondrosarcoma patients. CONCLUSION: Because
chondrosarcoma of bone is an orphan disease it is difficult to conduct clinical
trials. The meagre outcome data for locally advanced or metastatic patients
indicate that new treatment options are needed. For the phase I trials it is
difficult to draw conclusions because of the low numbers of chondrosarcoma
patients enrolled, and at different dose levels. Some phase II trials show
promising results which support further research. Retrospective studies are
encouraged as they could add to the limited data available. Efforts to increase
the number of studies for this orphan disease are urgently needed.
PMID- 25110576
TI - Functional characterization of Candida albicans Hos2 histone deacetylase.
AB - Candida albicans is a mucosal commensal organism capable of causing superficial
(oral and vaginal thrush) infections in immune normal hosts, but is a major
pathogen causing systemic and mucosal infections in immunocompromised
individuals. Azoles have been very effective anti-fungal agents and the mainstay
in treating opportunistic mold and yeast infections. Azole resistant strains have
emerged compromising the utility of this class of drugs. It has been shown that
azole resistance can be reversed by the co-administration of a histone
deacetylase (HDAC) inhibitor, suggesting that resistance is mediated by
epigenetic mechanisms possibly involving Hos2, a fungal deacetylase. We report
here the cloning and functional characterization of HOS2 (High Osmolarity
Sensitive) , a gene coding for fungal histone deacetylase from C. albicans.
Inhibition studies showed that Hos2 is susceptible to pan inhibitors such as
trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), but is not
inhibited by class I inhibitors such as MS-275. This in vitro enzymatic assay,
which is amenable to high throughput could be used for screening potent fungal
Hos2 inhibitors that could be a potential anti-fungal adjuvant. Purified Hos2
protein consistently deacetylated tubulins, rather than histones from TSA-treated
cells. Hos2 has been reported to be a putative NAD+ dependent histone
deacetylase, a feature of sirtuins. We assayed for sirtuin activation with
resveratrol and purified Hos2 protein and did not find any sirtuin activity.
PMID- 25126410
TI - Ring finger protein 39 genetic variants associate with HIV-1 plasma viral loads
and its replication in cell culture.
AB - BACKGROUND: The human immunodeficiency virus (HIV-1) exploits host proteins to
complete its life cycle. Genome-wide siRNA approaches suggested that host
proteins affect HIV-1 replication. However, the results barely overlapped. RING
finger protein 39 (RNF39) has been identified from genome-wide association
studies. However, its function during HIV-1 replication remains unclear. METHODS
AND RESULTS: We investigated the relationship between common RNF39 genetic
variants and HIV-1 viral loads. The effect of RNF39 protein knockdown or
overexpression on HIV-1 replication was then investigated in different cell
lines. Two genetic variants were associated with HIV-1 viral loads. Patients with
the ht1-GG/GG haplotype presented lower RNF39 expression levels and lower HIV-1
viral load. RNF39 knockdown inhibited HIV-1 expression. CONCLUSIONS: RNF39
protein may be involved in HIV-1 replication as observed in genetic studies on
patients with HIV-1 and in in vitro cell cultures.
PMID- 25110577
TI - Accumulation of oocytes and/or embryos by vitrification: a new strategy for
managing poor responder patients undergoing pre implantation diagnosis.
AB - BACKGROUND: Low (or poor) responder patients are women who require large doses of
stimulation medications and produce less than an optimal number of oocytes during
IVF cycles. Low responder patients produce few oocytes and embryos, which
significantly reduces their chances for success in a preimplantation genetic
diagnosis (PGD) cycle. Accumulation of vitrified oocytes or embryos before the
actual PGD cycle is a possible strategy that might increase patient's chances for
a healthy pregnancy. AIM OF THE STUDY: This retrospective study evaluates the
efficacy of a PGD program in low responder patients after repeated ovarian
stimulation cycles with cumulative vitrification of oocytes and embryos. METHODS:
Over a period of 30 months, 13 patients entering the PGD program were identified
as poor responders after their first ovarian stimulation. These patients started
a PGD cycle for one of the following indications: history of recurrent
implantation failure (n=1), cystic fibrosis (n=1), X-linked microtubular myopathy
(n=1), recurrent miscarriages (n=5), Duchene muscular dystrophy (n=1),
chromosomal translocation (n=1) and high sperm aneuploidy (n=1). After multiple
ovarian hormonal stimulations patients had either all mature oocytes (Group A; 3
patients) or all of their day 2 embryos vitrified (group B; 10 patients). Mean
total number of oocyte collections per patient was 2.3 (range: 2 - 5 cycles).
RESULTS: In the actual PGD cycle, all vitrified oocytes from group A patients
were warmed and underwent intra cytoplasmic sperm injection (ICSI) followed by
culture up to day 3. For group B patients all vitrified day 2 embryos were warmed
and cultured overnight. On day 3 of culture, all embryos from Group A and B had
blastomere biopsy followed by genetic analysis. In group A, 20 embryos were found
suitable for biopsy and genetic analysis; at least one healthy embryo was
available for transfer for each patient. For group B, 72 embryos in total were
available for biopsy and PGD. All patients, except one, had at least one healthy
day 5 embryo for transfer (mean number of 2.1 embryos per transfer). Nine
patients had a clinical pregnancy; 7 patients delivered a healthy baby.
CONCLUSION: Low responder patients entering a PGD program might increase their
chances for a healthy pregnancy by repeat ovarian stimulation in combination with
cumulative oocyte or embryo vitrification.
PMID- 25110576
TI - Functional characterization of Candida albicans Hos2 histone deacetylase.
AB - Candida albicans is a mucosal commensal organism capable of causing superficial
(oral and vaginal thrush) infections in immune normal hosts, but is a major
pathogen causing systemic and mucosal infections in immunocompromised
individuals. Azoles have been very effective anti-fungal agents and the mainstay
in treating opportunistic mold and yeast infections. Azole resistant strains have
emerged compromising the utility of this class of drugs. It has been shown that
azole resistance can be reversed by the co-administration of a histone
deacetylase (HDAC) inhibitor, suggesting that resistance is mediated by
epigenetic mechanisms possibly involving Hos2, a fungal deacetylase. We report
here the cloning and functional characterization of HOS2 (High Osmolarity
Sensitive) , a gene coding for fungal histone deacetylase from C. albicans.
Inhibition studies showed that Hos2 is susceptible to pan inhibitors such as
trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), but is not
inhibited by class I inhibitors such as MS-275. This in vitro enzymatic assay,
which is amenable to high throughput could be used for screening potent fungal
Hos2 inhibitors that could be a potential anti-fungal adjuvant. Purified Hos2
protein consistently deacetylated tubulins, rather than histones from TSA-treated
cells. Hos2 has been reported to be a putative NAD+ dependent histone
deacetylase, a feature of sirtuins. We assayed for sirtuin activation with
resveratrol and purified Hos2 protein and did not find any sirtuin activity.
PMID- 25126416
TI - Characterization of a multilayer heparin coating for biomolecule presentation to
human mesenchymal stem cell spheroids.
AB - Mesenchymal stem cells therapies have the potential to treat many pathologies,
however, controlling cell fate after implantation remains challenging. We have
used a multilayer technology to graft a range of 5 MUg/mL - 5 mg/mL heparin onto
the surface of MSC aggregates. Heparin coating does not affect cell viability
(seen through LIVE/DEAD staining), cell anti-inflammatory properties (seen
through co-culture with activated monocytes)and facilitates sequestration by
coated cells of a growth factor (TGF-beta1) that remains bioactive. This system
can maximize therapeutic potential of MSC-based treatments because the cell
surface-loaded protein could both signal to the cells to influence transplanted
cell fate and be released into the surrounding environment to help repair injured
tissue.
PMID- 25126414
TI - Cytoplasmic nanojunctions between lysosomes and sarcoplasmic reticulum are
required for specific calcium signaling.
AB - Herein we demonstrate how nanojunctions between lysosomes and sarcoplasmic
reticulum (L-SR junctions) serve to couple lysosomal activation to regenerative,
ryanodine receptor-mediated cellular Ca (2+) waves. In pulmonary artery smooth
muscle cells (PASMCs) it has been proposed that nicotinic acid adenine
dinucleotide phosphate (NAADP) triggers increases in cytoplasmic Ca (2+) via L-SR
junctions, in a manner that requires initial Ca (2+) release from lysosomes and
subsequent Ca (2+)-induced Ca (2+) release (CICR) via ryanodine receptor (RyR)
subtype 3 on the SR membrane proximal to lysosomes. L-SR junction membrane
separation has been estimated to be < 400 nm and thus beyond the resolution of
light microscopy, which has restricted detailed investigations of the junctional
coupling process. The present study utilizes standard and tomographic
transmission electron microscopy to provide a thorough ultrastructural
characterization of the L-SR junctions in PASMCs. We show that L-SR nanojunctions
are prominent features within these cells and estimate that the junctional
membrane separation and extension are about 15 nm and 300 nm, respectively.
Furthermore, we develop a quantitative model of the L-SR junction using these
measurements, prior kinetic and specific Ca (2+) signal information as input
data. Simulations of NAADP-dependent junctional Ca (2+) transients demonstrate
that the magnitude of these signals can breach the threshold for CICR via RyR3.
By correlation analysis of live cell Ca (2+) signals and simulated Ca (2+)
transients within L-SR junctions, we estimate that "trigger zones" comprising 60
100 junctions are required to confer a signal of similar magnitude. This is
compatible with the 110 lysosomes/cell estimated from our ultrastructural
observations. Most importantly, our model shows that increasing the L-SR
junctional width above 50 nm lowers the magnitude of junctional [Ca (2+)] such
that there is a failure to breach the threshold for CICR via RyR3. L-SR junctions
are therefore a pre-requisite for efficient Ca (2+)signal coupling and may
contribute to cellular function in health and disease.
PMID- 25126415
TI - Incidence and predictors of surgical site infections following caesarean sections
at Bugando Medical Centre, Mwanza, Tanzania.
AB - BACKGROUND: Surgical site infection (SSI) is the second most common infectious
complication after urinary tract infection following a delivery by caesarean
section (CS). At Bugando Medical Centre there has no study documenting the
epidemiology of SSI after CS despite the large number of CSs performed and the
relatively common occurrence of SSIs. METHODS: This was a prospective cohort
study involving pregnant women who underwent a CS between October 2011 and
February 2012 at Bugando Medical Centre. A total of 345 pregnant women were
enrolled. Preoperative, intraoperative and postoperative data were collected
using a standardized questionnaire. Wound specimens were collected and processed
as per standard operative procedures; and susceptibility testing was carried out
using a disc diffusion technique. Data was analyzed using STATA version 11.
RESULTS: The overall cumulative incidence of SSI was 10.9% with an incidence rate
of 37.5 per 10,000 people/day (95% CI, 26.8-52.4). The median time from CS to the
development of SSI was 7 days (interquartile range [IQR] = 6-9 days). Six
independent risk factors for post caesarean SSI as identified in this study by
multivariate analysis are: hypertensive disorders of pregnancy (HR: 2.5; 95% CI,
1.1-5.6; P = 0.021), severe anaemia (HR: 3.8; 95% CI, 1.2-12.4, P = 0.028),
surgical wound class III (HR: 2.4; 95% CI, 1.1-5.0; P = 0.021), multiple vaginal
examinations (HR: 2.5; 95% CI, 1.2-5.1; P = 0.011), prolonged duration of
operation (HR: 2.6; 95% CI, 1.2-5.5; P = 0.015) and an operation performed by an
intern or junior doctor (HR: 4.0; 95% CI, 1.7-9.2; P = 0.001). Staphylococcus
aureus was the most common organism (27.3%), followed by Klebsiella pneumoniae
(22.7%). Patients with a SSI had a longer average hospital stay than those
without a SSI (12.7 +/- 6.9 vs. 4 +/- 1.7; P < 0.0001) and the case fatality rate
among patients with a SSI was 2.9%. CONCLUSION: SSIs are common among women
undergoing CSs at Bugando Medical Centre. SSIs were commonly associated with
multiple factors. Strategies to control these factors are urgently needed to
control SSIs post CS at Bugando Medical Centre and other centres in developing
countries.
PMID- 25126417
TI - Mortality attributable to tobacco: review of different methods.
AB - BACKGROUND: One of the most important measures for ascertaining the impact of
tobacco is the estimation of the mortality attributable to its use. Several
indirect methods of quantification are available. The objective of the article is
to assess methodologies published and applied in calculating mortality
attributable to smoking. METHODS: A review of the literature was made for the
period 1998 to 2005, in the electronic databases MEDLINE. Twelve articles were
selected for analysis. RESULTS: The most widely used methods were the prevalence
methods, followed by smoking impact ration method. Ezzati and Lopez showed that
the general rate of Smoking attributable mortality (SAM) globally was 12% (18% in
men). Across countries, attributable fractions of total adult deaths ranged from
8% in Southern Africa, 13.6% in Brazil (18.1% in men) and 25% in Hong Kong (33%
in men). CONCLUSION: The variations can be attributed to methodological
differences and to different estimates of the main tobacco-related illnesses and
tobacco prevalence. All methods show limitations of one type or another, yet
there is no consensus as to which furnishes the best information.
PMID- 25126418
TI - Smoking-attributable mortality in Morocco: results of a prevalence-based study in
Casablanca.
AB - BACKGROUND: Tobacco control measurements' had little impact on smoking prevalence
in Morocco. The aim of this study is to provide first data on smoking
attributable mortality in Morocco. METHOD: The Smoking-Attributable Mortality,
Morbidity and Economic Costs (SAMMEC) software was used to estimate the smoking
attributable mortality (SAM) in Casablanca region in 2012. Smoking prevalence and
mortality data of people aged 35 years or older were obtained from the national
survey on tobacco "Marta" and from Health Ministry Mortality System,
respectively. RESULTS: Of the 5261deaths of persons aged 35 years and older, 508
(9.7%) were attributable to cigarette smoking. This total represents 16.2% of all
male deaths (n =448) and 2.0% (n =80) of all female deaths in this region. The
leading four causes of smoking attributable deaths were lung cancer (177),
chronic airways obstruction (76), ischemic heart disease (39), and
cerebrovascular disease (31). CONCLUSION: Tobacco use caused one out of six
deaths in Casablanca in 2012. Four leading causes (lung cancer, ischemic heart
disease, cerebrovascular disease and chronic airways obstruction,) accounted for
51.6% of SAM. Effective and comprehensive actions must be taken in order to slow
this epidemic in Morocco.
PMID- 25126419
TI - A Centre for the Diagnosis and Treatment of Tuberculosis (CDT) in a resource
limited setting: a dragnet for patients with heart disease?
AB - BACKGROUND: Cardiovascular disease is a growing public health problem in sub
Saharan Africa. Cough and dyspnea are symptoms of both lung diseases and heart
failure. This study aimed at determining the contribution of cardiac diseases
versus pulmonary diseases in the etiological profile of patients presenting with
cough and dyspnea in a Center for the Diagnosis and Treatment of Tuberculosis
(CDT), in a semi-rural area in Cameroon. METHODS: This is a cross-sectional
analysis of data from patients aged 18 years or more who consulted for cough and
or dyspnea between December 2009 and December 2010 at the CDT of Lafe-Baleng,
Bafoussam, Cameroon. RESULTS: A total of 1196 patients were received for various
complaints during the study period; 348 (29.1%) of them presented with cough and
or dyspnea, and were included in the study. 186 patients (53.4%; 95% CI: 48.2
58.6) had a pure cardiac disease, while 122 patients (35.1%; 95% CI: 30.2-40.2)
had a pulmonary disease. The prevalence of hypertension was 50.9%, and
hypertensive heart disease was the most frequent cardiac disease with a
prevalence rate of 37.6%. Heart failure was diagnosed in 222 patients,
representing 63.8% (95% CI: 58.9-68.9) of patients with cough and or dyspnea, and
18.6% (95% CI: 16.5-21.0) of all the patients received at the CDT of Lafe-Baleng
during the study period. Compared to patients with a pulmonary disease, patients
with cardiac disease were older (p < 0.001) and more likely to present with
dyspnea (p < 0.001) and to have hypertension (p < 0.001). CONCLUSION: We found a
high prevalence of heart failure in this Centre for the Diagnosis and Treatment
of Tuberculosis thus, a veritable dragnet for patients with heart disease. Our
findings emphasize the urgent need to increase the access to cardiovascular care
and to continuously raise the awareness of the communities on cardiovascular
diseases in Cameroon.
PMID- 25126420
TI - Impact of community-based interventions on HIV knowledge, attitudes, and
transmission.
AB - In 2012, an estimated 35.3 million people lived with HIV, while approximately two
million new HIV infections were reported. Community-based interventions (CBIs)
for the prevention and control of HIV allow increased access and ease
availability of medical care to population at risk, or already infected with,
HIV. This paper evaluates the impact of CBIs on HIV knowledge, attitudes, and
transmission. We included 39 studies on educational activities, counseling
sessions, home visits, mentoring, women's groups, peer leadership, and street
outreach activities in community settings that aimed to increase awareness on
HIV/AIDS risk factors and ensure treatment adherence. Our review findings suggest
that CBIs to increase HIV awareness and risk reduction are effective in improving
knowledge, attitudes, and practice outcomes as evidenced by the increased
knowledge scores for HIV/AIDS (SMD: 0.66, 95% CI: 0.25, 1.07), protected sexual
encounters (RR: 1.19, 95% CI: 1.13, 1.25), condom use (SMD: 0.96, 95% CI: 0.03,
1.58), and decreased frequency of sexual intercourse (RR: 0.76, 95% CI: 0.61,
0.96). Analysis shows that CBIs did not have any significant impact on scores for
self-efficacy and communication. We found very limited evidence on community
based management for HIV infected population and prevention of mother- to-child
transmission (MTCT) for HIV-infected pregnant women. Qualitative synthesis
suggests that establishment of community support at the onset of HIV prevention
programs leads to community acceptance and engagement. School-based delivery of
HIV prevention education and contraceptive distribution have also been advocated
as potential strategies to target high-risk youth group. Future studies should
focus on evaluating the effectiveness of community delivery platforms for
prevention of MTCT, and various emerging models of care to improve morbidity and
mortality outcomes.
PMID- 25126423
TI - Evaluation of the new digital goldmann applanation tonometer for measuring
intraocular pressure.
AB - Purpose. To compare a new digital Goldmann applanation tonometer (dGAT) that
measures intraocular pressure (IOP) in 0.1 mmHg increments to a standard Goldmann
applanation tonometer (sGAT). Methods. This study included 116 eyes of 60
subjects. A single examiner first measured IOP in triplicate using either sGAT or
dGAT, which was randomly chosen. After a 5-minute interval, the next set of three
consecutive IOP was measured using the other GAT. Results. The mean IOP measured
with sGAT was 16.27 +/- 6.68 mmHg and 16.35 +/- 6.69 mmHg with dGAT. Pearson's
correlation coefficient was 0.998 (P < 0.01). The subjects were divided into
three groups based on the mean IOP: IOP < 14 mmHg, 14-20 mmHg, or >20 mmHg. The
Pearson's correlation coefficient within each group was 0.935, 0.972, and 0.997
(P < 0.01), respectively. The difference within the three consecutive IOP
measurements (maximum-minimum) for dGAT (0.72 +/- 0.34 mmHg) was significantly
smaller than those with sGAT (0.92 +/- 0.42 mmHg, P < 0.01). Even in patients
with equal IOP (zero left-right difference) with sGAT (n = 30), dGAT detected IOP
differences between the left and right eyes (0.47 +/- 0.31 mmHg). Conclusion.
Compared to sGAT, dGAT measurements are highly reproducible and less variable.
PMID- 25126421
TI - A melanoma helper peptide vaccine increases Th1 cytokine production by leukocytes
in peripheral blood and immunized lymph nodes.
AB - BACKGROUND: Cancers produce soluble and cell-associated molecules that can
suppress or alter antitumor immunity. Preclinical studies suggest the disease
burden may alter the cytokine profile of helper T cell responses to cancer
antigens. We studied cytokine production by helper T cells responding to
vaccination with 6 melanoma helper peptides (6MHP) in blood and lymph nodes.
METHODS: Twenty-three patients with stage IIIB-IV melanoma received a 6MHP
vaccine. Antigen-reactive T cells from blood and draining lymph nodes were
cultured, exposed to antigen, and then supernatants (days 2 and 5) were assayed
for Th1 and Th2 cytokines. Results from 4 time points were compared to pre
vaccine levels. RESULTS: Cytokine responses to vaccinating peptides were observed
in 83% of patients. Th1 favoring responses were most common (17 of 19
responders). The most abundant cytokines produced were IFN-gamma and IL-5 in the
PBMC's. IL-2 responses predominated in cells obtained from draining lymph nodes
in 2-day culture but not in 5-day cultures. Patients with clinically measurable
disease produced similar levels of total cytokine and similar degree of Th1
polarization as patients with no evidence of disease (NED). CONCLUSIONS: The MHC
class II-associated peptides used in this study induced helper T cells with a Th1
biased cytokine response in both PBMC and sentinel immunized nodes. Most patients
can mount a Th1 dominant response to these peptides. Future studies are needed to
test newer vaccine adjuvants in combination with these peptides. TRIAL
REGISTRATION: CDR0000378171, Clinicaltrials: NCT00089219.
PMID- 25126422
TI - Psychogenic Stress in Hospitalized Dogs: Cross Species Comparisons, Implications
for Health Care, and the Challenges of Evaluation.
AB - Evidence to support the existence of health consequences of psychogenic stress
has been documented across a range of domestic species. A general understanding
of methods of recognition and means of mitigation of psychogenic stress in
hospitalized animals is arguably an important feature of the continuing efforts
of clinicians to improve the well-being and health of dogs and other veterinary
patients. The intent of this review is to describe, in a variety of species: the
physiology of the stress syndrome, with particular attention to the hypothalamic
pituitary-adrenal axis; causes and characteristics of psychogenic stress;
mechanisms and sequelae of stress-induced immune dysfunction; and other adverse
effects of stress on health outcomes. Following that, we describe general aspects
of the measurement of stress and the role of physiological measures and
behavioral signals that may predict stress in hospitalized animals, specifically
focusing on dogs.
PMID- 25126424
TI - Pain and Anxiety versus Sense of Family Support in Lung Cancer Patients.
AB - Lung cancer is a stressful condition for both patient and family. The anxiety and
pain accompanying cancer and its treatment have a significant negative influence
on the patient's quality of life. The aim of this study was to investigate the
correlation between anxiety, pain, and perceived family support in a sample of
lung cancer patients. The sample consisted of a total of 101 lung cancer
outpatients receiving treatment at the oncology department of a general hospital.
Anxiety, pain (severity and impact on everyday life), and perceived family
support were assessed using Spielberger's State-Trait Anxiety Inventory, the
Brief Pain Inventory, and the Family Support Scale, respectively. Statistical
analyses revealed correlations between anxiety, pain, and family support as
perceived by the patients. The intensity of pain had a positive correlation with
both state and trait anxiety and a negative correlation with family support.
Anxiety (state and trait) had a significant negative correlation with family
support. In conclusion, high prevalence rates of anxiety disorders were observed
in lung cancer patients. Females appeared more susceptible to anxiety symptoms
with a less sense of family support. A negative correlation was evidenced between
family support and anxiety and a positive one between anxiety and pain.
PMID- 25126425
TI - Gestational trophoblastic disease: a multimodality imaging approach with impact
on diagnosis and management.
AB - Gestational trophoblastic disease is a condition of uncertain etiology, comprised
of hydatiform mole (complete and partial), invasive mole, choriocarcinoma, and
placental site trophoblastic tumor. It arises from abnormal proliferation of
trophoblastic tissue. Early diagnosis of gestational trophoblastic disease and
its potential complications is important for timely and successful management of
the condition with preservation of fertility. Initial diagnosis is based on a
multimodality approach: encompassing clinical features, serial quantitative beta
hCG titers, and pelvic ultrasonography. Pelvic magnetic resonance imaging (MRI)
is sometimes used as a problem-solving tool to assess the depth of myometrial
invasion and extrauterine disease spread in equivocal and complicated cases.
Chest radiography, body computed tomography (CT), and brain MRI have been
recommended as investigative tools for overall disease staging. Angiography has a
role in management of disease complications and metastases. Efficacy of PET
(positron emission tomography) and PET/CT in the evaluation of recurrent or
metastatic disease has not been adequately investigated yet. This paper discusses
the imaging features of gestational trophoblastic disease on various imaging
modalities and the role of different imaging techniques in the diagnosis and
management of this entity.
PMID- 25126426
TI - Saphenous vein sparing superficial inguinal dissection in lower extremity
melanoma.
AB - Aim. The classic inguinal lymph node dissection is the main step for the regional
control of the lower extremity melanoma, but this surgical procedure is
associated with significant postoperative morbidity. The permanent lymphedema is
the most devastating long-term complication leading to a significant decrease in
the patient's quality of life. In this study we present our experience with
modified, saphenous vein sparing, inguinal lymph node dissections for patients
with melanoma of the lower extremity. Methods. Twenty one patients (10 women, 11
men) who underwent saphenous vein sparing superficial inguinal lymph node
dissection for the melanoma of lower extremity were included in this study. The
effects of saphenous vein sparing on postoperative complications were evaluated.
Results. We have observed the decreased rate of long-term lymphedema in patients
undergoing inguinal lymphadenectomy for the lower extremity melanoma. Conclusion.
The inguinal lymphadenectomy with saphenous vein preservation in lower extremity
melanoma patients seems to be an oncologically safe procedure and it may offer
reduced long-term morbidity.
PMID- 25126427
TI - Daytime sleepiness and Parkinson's disease: the contribution of the multiple
sleep latency test.
AB - Background. Sleep disorders are major nonmotor manifestations of patients with
Parkinson's disease (PD), and excessive daytime sleepiness (EDS) is one of the
most common symptoms. Objective. We reviewed a current literature concerning
major factors that influence EDS in PD patients, using Multiple Sleep Latency
Test (MSLT). Methods. A Medline search found 23 studies. Results. The presence of
EDS was observed in 12.7% to 47% in patients without complaints of daytime
sleepiness and 47% to 66.7% with complaints of daytime sleepiness. Despite being
recognized by several authors, major factors that influence EDS, such as severity
of motor symptoms, use of dopaminergic medications, and associated sleep
disturbances, presented contradictory data. Conclusions. Available data suggest
that the variability of the results may be related to the fact that it was
conducted with a small sample size, not counting the neuropathological
heterogeneity of the disease. Thus, before carrying out longitudinal studies with
significant samples, careful analysis should be done by assigning a specific
agent on the responsibility of EDS in PD patients.
PMID- 25126428
TI - Schwannoma of the tongue in a paediatric patient: a case report and 20-year
review.
AB - Schwannomas (Neurilemmomas) are benign, encapsulated, slow-growing, and usually
solitary tumours originating from Schwann cells of the peripheral nerve sheath
with uncertain etiology. Approximately 25-48% of cases are seen in the head and
neck region, of which 1% appears in the oral cavity. Lingual schwannoma can
affect all age groups with peak incidence between the third and sixth decade. We
report a rare case of lingual schwannoma in a 14-year-old girl complaining of
asymptomatic swelling over lateral border of tongue since two years. Clinical
examination revealed a nodule 1.5 * 1 cm in size, rubbery, nontender, smooth at
right lateral border of tongue covered by normal mucosa, with no cervical
lymphadenopathy. Excisional biopsy of the lesion was done under local
anaesthesia. The histological sections spindle cells with thin wavy nuclei
arranged as typical Antoni A (with Verocay bodies) and Antoni B areas. Nuclear
palisading distribution (typical of a schwannoma) was readily identifiable. The
patient was recurrence-free after one year.
PMID- 25126430
TI - Transient global amnesia associated with an acute infarction at the cingulate
gyrus.
AB - Background. Transient global amnesia (TGA) is a syndrome of sudden, unexplained
isolated short-term memory loss. In the majority of TGA cases, no causes can be
identified and neuroimaging, CSF studies and EEG are usually normal. We present a
patient with TGA associated with a small acute infarct at the cingulate gyrus.
Case Report. The patient, a 62 year-old man, developed two episodes of TGA. He
had hypertension and hypercholesterolemia. He was found to have an acute ischemic
stroke of small size (15 mm of maximal diameter) at the right cerebral cingulate
gyrus diagnosed on brain magnetic resonance imaging. No lesions involving other
limbic system structures such as thalamus, fornix, corpus callosum, or
hippocampal structures were seen. The remainder of the examination was normal.
Conclusion. Unilateral ischemic lesions of limbic system structures may result in
TGA. We must bear in mind that TGA can be an associated clinical disorder of
cingulate gyrus infarct.
PMID- 25126429
TI - An Uncommon Presentation of Spontaneous Rectus Sheath Hematoma with Acute Kidney
Injury due to Obstructive Uropathy and Prerenal Azotemia.
AB - Rectus Sheath Hematoma (RSH) represents an unusual entity which is characterized
by acute abdominal pain and tender palpable abdominal mass usually, among elderly
patients receiving anticoagulant therapy. We report the case of an 81-year-old
woman admitted to our department due to acute abdominal pain and oligoanuria. The
patient had recently been hospitalized due to acute myocardial infarction (AMI)
and atrial fibrillation (AF) and received both anticoagulant and antiplatelet
therapies. The radiological assessments revealed an extended Rectus Sheath
Hematoma and bilateral hydronephrosis. Treatment of the hematoma required
cessation of anticoagulants and antiplatelet agents, immobilization, blood and
fresh frozen plasma transfusion, and administration of vasopressors. The patient
recovered gradually and was discharged home fifteen (15) days later.
PMID- 25126431
TI - Listerial rhombencephalitis in an immunocompetent woman.
AB - Listeriosis usually affects immunocompromised patients including elderly people
and pregnant women, but it may also affect otherwise healthy individuals. In our
report, we present a case of a rare and very severe form of listeriosis
rhombencephalitis in a 61-year-old female with no history of immunosuppression,
who, because of history, clinical picture, and laboratory results as well as
negative cultures, was at first diagnosed with viral encephalitis. This paper
underlines that Listeria monocytogenes infection should be taken into
consideration in case of lymphocytic encephalitis even in immunocompetent
patients. Typical MRI picture may be crucial in establishing a proper diagnosis
as the lab results may be misleading.
PMID- 25126432
TI - Disseminated intravascular coagulopathy caused by uterine leiomyoma with sarcoma
like findings on magnetic resonance imaging.
AB - A leiomyoma rarely causes disseminated intravascular coagulopathy (DIC). In the
present report, we describe a case of DIC caused by leiomyoma. A 36-year-old
nulliparous woman presented with hypermenorrhea and a lower abdominal mass. On
magnetic resonance imaging, we detected a 14 cm uterine tumor, which was
suspected to be a sarcoma. Blood tests at the preoperative examination indicated
platelet count of 9.6 * 10(4)/MUL, fibrin degradation product level of 107.1
MUg/mL (normal value, 0-5.0 MUg/mL), and fibrinogen level of 54 mg/dL (normal
value, 129-271 mg/dL). Based on these findings, we diagnosed the patient with
DIC. The patient was treated with nafamostat mesilate and fresh frozen plasma,
but the DIC did not show any improvement. Subsequently, a hysterectomy was
performed, after which the DIC improved. Clinicopathological findings indicated
the presence of a leiomyoma with multiple vessels containing thromboemboli, and
suggested that the DIC was caused by the leiomyoma. Therefore, it is essential to
consider that that a benign leiomyoma may be a cause of DIC.
PMID- 25126433
TI - Ocular trauma from the "knockout game".
AB - The "knockout game" is a new form of urban violence receiving much attention in
local and national media. Apart from the obvious head trauma, eye injuries may be
subtle and overlooked. This report brings awareness of potential eye damage with
this type of assault. This report is of a young woman, victim of the knockout
game, who sustained a submacular hemorrhage. Beyond a neurologic evaluation for
anyone knocked unconscious following the knockout game, patients should be
counseled regarding potential ocular injury and encouraged to seek eye care
promptly should symptoms develop.
PMID- 25126434
TI - An unusual presentation of charcot arthropathy caused by syringomyelia mimicking
a soft tissue tumor.
AB - Charcot arthropathy is a chronic, degenerative condition and is associated with
decreased sensorial innervation. Numerous causes of this arthropathy have been
described. Here we report a case of neuropathic arthropathy secondary to
syringomyelia which was misdiagnosed as a soft tissue tumor and treated
surgically and additionally with radiotherapy at another institution. The patient
had clinical and radiological signs of syringomyelia, associated with a limited
range of motion, swelling, and pain in the affected joint. Neuropathic
arthropathy, although less common, should be considered in cases of unexplained
joint swelling, pain, and limited range of motion of the affected joint.
PMID- 25126435
TI - Endoscopic CO(2) Laser Horizontal Partial Laryngectomy in Larynx Carcinosarcoma.
AB - Background. Carcinosarcoma is an extremely rare malignant neoplasm, with both a
malignant epithelial and mesenchymal component, that rarely affects the larynx.
Aim. Aim of this paper is to describe the case of a patient affected by a larynx
carcinosarcoma treated by endoscopic horizontal partial laryngectomy with CO(2)
laser and particularly discuss the histogenetic hypothesis as well as the
possible treatment modalities of this rare lesion. Methods. Case report and
literature review. Discussion and Conclusion. Still little is known about the
biology of carcinosarcoma and there is still no consensus in the literature on
the treatment of these tumors. Endoscopic horizontal partial laryngectomy could
represent another treatment option in selected cases.
PMID- 25126436
TI - Intracranial gliofibroma: a case report and review of the literature.
AB - Gliofibroma is a rare tumor with biphasic morphology, commonly occurring in the
first two decades of life. Currently, the tumor is not listed as a distinct
entity in the current World Health Organization (WHO) classification of central
nervous system tumors. As its biological behavior, histogenesis, and prognostic
factors are still debated, the aim of this paper was to describe a case of a
gliofibroma and to update the data about these lesions. Hence, we present here
clinical symptoms, pathological findings, and evolution observed in a child with
gliofibroma. A 10-year-old girl with seizures was referred for study.
Neuroimaging showed a hemispheric hyperdense tumor with little peritumoral edema
and no mass effect. The tumor was totally removed. Histologically, the tumor
consisted of a mixture of glial cells and collagen-rich stroma.
Immunohistochemical examination revealed positive staining for GFAP, CD 99, S100,
and vimentin. EMA staining showed a paranuclear dot pattern in only few cells in
isolated areas. These findings of a glial component with collagenous stroma were
consistent with a desmoplastic glioma. Because of the rarity of this entity, we
believe it is important to report every case in order to adequately analyze and
categorize the tumor in the next WHO classification.
PMID- 25126437
TI - High-Flow Nasal Cannula Therapy in a Patient with Reperfusion Pulmonary Edema
following Percutaneous Transluminal Pulmonary Angioplasty.
AB - A 62-year-old woman with Wolff-Parkinson-White syndrome was with recent worsening
of dyspnea to New York Heart Association functional status Class III. The patient
was diagnosed as having central type chronic thromboembolic pulmonary
hypertension. By cardiac catheterization, her mean pulmonary artery pressure was
53 mmHg with total pulmonary resistance 2238 dynes.sec.cm(-5). After medical
therapies with tadalafil, furosemide, ambrisentan, beraprost, and warfarin were
initiated, percutaneous transluminal pulmonary angioplasty (PTPA) was performed.
Following PTPA, life-threating hypoxemia resulting from postoperative reperfusion
pulmonary edema developed. High-flow nasal cannula therapy (HFNC) was applied,
and 100% oxygen at 50 L/min of flow was required to keep oxygenation. HFNC was
continued for 3 days, and the patient was discharged on 8th postoperative day
with SpO2 of 97% on 3 L/min of oxygen inhalation. Because of the simplicity of
the technique, the lower cost of equipment, and remarkable patient tolerance to
the treatment, we speculate that HFNC can take over the post of noninvasive
ventilation as first-line therapy for patients with acute respiratory failure.
PMID- 25126438
TI - Tuber cinereum diverticula in a 28-month-old with xq21 deletion syndrome.
AB - A developmentally delayed 28-month-old male toddler was referred to us for brain
MRI. Imaging revealed corpus callosum dysgenesis, forniceal hypoplasia, vermian
hypoplasia, and hypothalamic dysmorphism characterized by tuber cinereum
diverticula. Subsequent chromosomal microarray showed an Xq21 deletion. We
present a case of Xq21 deletion syndrome with midline brain anomalies and a novel
hypothalamic malformation.
PMID- 25126439
TI - Isolated nasopharyngeal castleman disease: an uncommon diagnosis in an unusual
location.
AB - Localised nasopharyngeal Castleman disease has rarely been reported. We present a
case involving a 23-year-old female, describe the clinical, imaging, and
histopathologic features of this challenging diagnosis, and review the
literature.
PMID- 25126440
TI - Antenatal diagnosis of alobar holoprosencephaly.
AB - A twenty-year-old second gravida presented to the department of radiodiagnosis
for routine obstetric ultrasound examination. Ultrasonography revealed a live
fetus of 17 weeks with absent falx, fused thalami, monoventricle, proboscis, and
cyclopia. Fetal MRI was performed and the findings were confirmed. Even though
ultrasonography is diagnostic in the detection of fetal anomalies, MRI plays a
vital role due to its multiplanar capability and excellent soft tissue
resolution. The importance of presenting this classical case of alobar
holoprosencephaly is to sensitize the clinicians and radiologists to the imaging
manifestations of holoprosencephaly and to stress the importance of early
diagnosis. If diagnosed in utero at an early stage of pregnancy, termination can
be performed and maternal psychological trauma of bearing a deformed fetus can be
avoided.
PMID- 25126441
TI - Cecal endometriosis presenting as acute appendicitis.
AB - The aim of our paper is to show the diagnosis of Coecal endometriosis as an
infrequent reason of right iliac fossa pain. cecal endometriosis manifesting with
right lower quadrant pain is difficult to diagnose, and it may even sometimes
require laparotomy for diagnosis and treatment. We report here a case of cecal
endometriosis causing clinically resembled acute appendicitis. In our patient, a
diagnosis of cecal endometriosis was made postoperatively by microscopic
examination of excised right colon, and the patient symptoms and general
condition were improved after the surgery (open right hemicolectomy and ileocolic
anastomosis).
PMID- 25126442
TI - Yersinia enterocolitica Infection Simulating Lymphoproliferative Disease, after
Liver Transplant.
AB - We describe a 14-year-old girl, who was 13 y after liver transplantation for
biliary atresia with an unremarkable postoperative course. She presented with
fever of up to 40 degrees C, extreme fatigue, malaise, anorexia, and occasional
vomiting. On physical examination the only finding was splenomegaly. Lab results
showed hyperglobulinemia and an elevated sedimentation rate. Liver function tests
were normal except for mild elevation of gammaGTP. Abdominal U/S and CT
demonstrated an enlarged spleen with retroperitoneal and mesenteric lymph nodes
enlargement. An exhaustive evaluation for infectious causes, autoimmune
conditions, and malignancy was negative. A full recovery after 5 months prompted
testing for self-limited infectious etiologies. Yersinia enterocolitica infection
was diagnosed.
PMID- 25126443
TI - Autologous bone marrow mononuclear cells intrathecal transplantation in chronic
stroke.
AB - Cell therapy is being widely explored in the management of stroke and has
demonstrated great potential. It has been shown to assist in the remodeling of
the central nervous system by inducing neurorestorative effect through the
process of angiogenesis, neurogenesis, and reduction of glial scar formation. In
this study, the effect of intrathecal administration of autologous bone marrow
mononuclear cells (BMMNCs) is analyzed on the recovery process of patients with
chronic stroke. 24 patients diagnosed with chronic stroke were administered cell
therapy, followed by multidisciplinary neurorehabilitation. They were assessed on
functional independence measure (FIM) objectively, along with assessment of
standing and walking balance, ambulation, and hand functions. Out of 24 patients,
12 improved in ambulation, 10 in hand functions, 6 in standing balance, and 9 in
walking balance. Further factor analysis was done. Patients of the younger groups
showed higher percentage of improvement in all the areas. Patients who underwent
cell therapy within 2 years after the stroke showed better changes. Ischemic type
of stroke had better recovery than the hemorrhagic stroke. This study
demonstrates the potential of autologous BMMNCs intrathecal transplantation in
improving the prognosis of functional recovery in chronic stage of stroke.
Further clinical trials are recommended. This trial is registered with
NCT02065778.
PMID- 25126444
TI - Development of the rat model of lapatinib-induced diarrhoea.
AB - Targeted therapy of cancer is often associated with clinically significant
diarrhoea; however, the mechanisms underpinning this adverse effect are currently
unknown. Diarrhoea following treatment with tyrosine kinase inhibitors (TKIs) of
EGFR is particularly troublesome. Until recently, understanding of EGFR TKI
induced diarrhoea has been limited to clinical observation. However, our group
has recently developed the first rat model of EGFR TKI-induced diarrhoea. This
paper reviews the published and unpublished findings.
PMID- 25126445
TI - Transforming traditional Tai Ji Quan techniques into integrative movement therapy
Tai Ji Quan: Moving for Better Balance.
AB - Tai Ji Quan, developed as a martial art, has traditionally served multiple
purposes, including self-defense, competition/performance, and health promotion.
With respect to health, the benefits historically and anecdotally associated with
Tai Ji Quan are now being supported by scientific and clinical research, with
mounting evidence indicating its potential value in preventing and managing
various diseases and improving well-being and quality of life in middle-aged and
older adults. The research findings produced to date have both public health
significance and clinical relevance. However, because of its roots in the martial
arts, transforming traditional Tai Ji Quan movements and training approaches into
contemporary therapeutic programs and functional applications is needed to
maximize its ultimate utility. This paper addresses this issue by introducing Tai
Ji Quan: Moving for Better Balance, a functional therapy that involves the use of
Tai Ji Quan principles and Yang-style-based movements to form an innovative,
contemporary therapeutic approach that integrates motor, sensory, and cognitive
components to improve postural control, gait, and mobility for older adults and
those who have neurodegenerative movement impairments. It provides a synergy of
traditional and contemporary Tai Ji Quan practice with the ultimate goal of
improving balance and gait, enhancing performance of daily functional tasks, and
reducing incidence of falls among older adults.
PMID- 25126446
TI - Teleoperation System with Hybrid Pneumatic-Piezoelectric Actuation for MRI-Guided
Needle Insertion with Haptic Feedback.
AB - This paper presents a surgical master-slave tele-operation system for
percutaneous interventional procedures under continuous magnetic resonance
imaging (MRI) guidance. This system consists of a piezoelectrically actuated
slave robot for needle placement with integrated fiber optic force sensor
utilizing Fabry-Perot interferometry (FPI) sensing principle. The sensor flexure
is optimized and embedded to the slave robot for measuring needle insertion
force. A novel, compact opto-mechanical FPI sensor interface is integrated into
an MRI robot control system. By leveraging the complementary features of
pneumatic and piezoelectric actuation, a pneumatically actuated haptic master
robot is also developed to render force associated with needle placement
interventions to the clinician. An aluminum load cell is implemented and
calibrated to close the impedance control loop of the master robot. A force
position control algorithm is developed to control the hybrid actuated system.
Teleoperated needle insertion is demonstrated under live MR imaging, where the
slave robot resides in the scanner bore and the user manipulates the master
beside the patient outside the bore. Force and position tracking results of the
master-slave robot are demonstrated to validate the tracking performance of the
integrated system. It has a position tracking error of 0.318mm and sine wave
force tracking error of 2.227N.
PMID- 25126447
TI - Evaluating an Integrative Theoretical Framework for HIV Sexual Risk among
Juvenile Justice involved Adolescents.
AB - Juvenile justice involved youth are at great risk for negative outcomes of risky
sexual behavior including HIV/AIDS. Given the strong connection between alcohol
use and risky sex in this population, it is important to consider alcohol use in
interventions designed to decrease risky sexual behavior. This paper provides
support for an integrative translational model that incorporates psychosocial,
neurobiological, and genetic factors to better predict alcohol-related sexual
risk behavior. Specifically, we present the design, methods, and baseline data
from a complex randomized control trial, Project SHARP (Sexual Health and
Adolescent Risk Prevention) in order to illustrate how this broad array of
factors can best predict alcohol-related sexual risk behavior. Participants were
justice-involved adolescents (n=284) who completed an fMRI and self-report
assessments prior to randomization to either a sexual risk plus alcohol risk
reduction group intervention or to an information-only contact control group
intervention. Structural equation modeling was utilized and findings supported
the hypothesized relationships in the translational model. Preliminary data
suggest that interventions among justice-involved adolescents targeting alcohol
related sexual risk behavior may be more effective if a biopsychosocial approach
is considered.
PMID- 25126448
TI - Dallas Glaucoma Registry: Preliminary Results.
AB - BACKGROUND: Although glaucoma is a leading cause of blindness worldwide, yet
there are no large databases where risk factors, current management options and
outcomes may be evaluated. With this concept in mind, Dallas Glaucoma Registry
was established to focus on an ethnically mixed North Texas population. METHODS:
This is a retrospective, chart review of 2,484 patients (4,839 eyes) with
glaucoma from three clinics. Data collected included: age, race, gender,
intraocular pressure, visual acuity, central corneal thickness, cup-to-disk
ratio, extent of visual field damage, glaucoma diagnoses, medical and surgical
therapies. RESULTS: The most prevalent glaucoma was primary open angle glaucoma
accounting for 44.4% of patients, followed by glaucoma suspect (39.5%), secondary
glaucoma (7.2%), angle closure glaucoma (6.8%), normal tension glaucoma (1.7%),
and childhood glaucoma (0.5%). The mean (SD) age was 68.7 (13.8) and 41.3% were
non Hispanic white, 37.0% were black, 10.4% were Hispanic and 11.3% were of other
ethnic origin. Hispanic representation in glaucoma did not match their numbers in
general population of North Texas. CONCLUSION: Large numbers of patients in the
ongoing Dallas Glaucoma Registry do provide adequate data to better understand
risk factors, early detection, improved screening targets, treatment options,
outcomes and future studies.
PMID- 25126451
TI - Dermatopathology: An abridged compendium of words. A discussion of them and
opinions about them. Part 5.
PMID- 25126450
TI - A headset method for measuring the visual temporal discrimination threshold in
cervical dystonia.
AB - BACKGROUND: The visual temporal discrimination threshold (TDT) is the shortest
time interval at which one can determine two stimuli to be asynchronous and meets
criteria for a valid endophenotype in adult-onset idiopathic focal dystonia, a
poorly penetrant disorder. Temporal discrimination is assessed in the hospital
laboratory; in unaffected relatives of multiplex adult-onset dystonia patients
distance from the hospital is a barrier to data acquisition. We devised a
portable headset method for visual temporal discrimination determination and our
aim was to validate this portable tool against the traditional laboratory-based
method in a group of patients and in a large cohort of healthy controls. METHODS:
Visual TDTs were examined in two groups 1) in 96 healthy control participants
divided by age and gender, and 2) in 33 cervical dystonia patients, using two
methods of data acquisition, the traditional table-top laboratory-based system,
and the novel portable headset method. The order of assessment was randomized in
the control group. The results obtained by each technique were compared. RESULTS:
Visual temporal discrimination in healthy control participants demonstrated
similar age and gender effects by the headset method as found by the table-top
examination. There were no significant differences between visual TDTs obtained
using the two methods, both for the control participants and for the cervical
dystonia patients. Bland-Altman testing showed good concordance between the two
methods in both patients and in controls. DISCUSSION: The portable headset device
is a reliable and accurate method for visual temporal discrimination testing for
use outside the laboratory, and will facilitate increased TDT data collection
outside of the hospital setting. This is of particular importance in multiplex
families where data collection in all available members of the pedigree is
important for exome sequencing studies.
PMID- 25126449
TI - The determinants of head and neck cancer: Unmasking the PI3K pathway mutations.
AB - Studies attempting to identify and understand the function of mutated genes and
deregulated molecular pathways in cancer have been ongoing for many years. The
PI3K-PTEN-mTOR signaling pathway is one of the most frequently deregulated
pathways in cancer. PIK3CA mutations are found 11%-33% of head and neck cancer
(HNC). The hotspot mutation sites for PIK3CA are E542K, E545K and H1047R/L. The
PTEN somatic mutations are in 9-23% of HNC, and they frequently cluster in the
phosphatase domain of PTEN protein. PTEN loss of heterozygosity (LOH) ranges from
41%-71% and loss of PTEN protein expression occurs in 31.2% of the HNC samples.
PIK3CA and PTEN are key molecules in the PI3K-PTEN-mTOR signaling pathway. In
this review, we provided a comprehensive overview of mutations in the PI3K-PTEN
mTOR molecular circuitry in HNC, including PI3K family members, TSC1/TSC2, PTEN,
AKT, and mTORC1 and mTORC2 complexes. We discussed how these genetic alterations
may affect protein structure and function. We also highlight the latest
discoveries in protein kinase and tumor suppressor families, emphasizing how
mutations in these families interfere with PI3K signaling. A better understanding
of the mechanisms underlying cancer formation, progression and resistance to
therapy will inform selection of novel genomic-based personalized therapies for
head and neck cancer patients.
PMID- 25126453
TI - Acantholytic dyskeratotic acanthoma: case report and review of the literature.
AB - BACKGROUND: Focal acantholytic dyskeratosis has been described as an incidental
finding and as a clinically distinct lesion. In both situations, a dimorphic
histologic pattern is observed: acantholysis and dyskeratosis. Solitary, non
genital lesions displaying such pathology have been difficult to classify.
Clinical and pathological characteristics of acantholytic dyskeratotic acanthomas
are described. METHODS: The features of a patient with solitary, non-genital,
acantholytic dyskeratotic acanthoma are presented and the literature on
acantholytic dyskeratotic acanthomas is reviewed. Using PubMed the following
terms were searched and relevant citations assessed: acantholysis, acanthoma,
cutaneous, dyskeratosis, nail, warty. RESULTS: We identified 30 cutaneous
acantholytic dyskeratotic acanthomas, including our patient, most often found on
the trunk and mimicking basal cell carcinoma, and three subungual acantholytic
dyskeratotic acanthomas of the thumb, which mimicked onychopapilloma. CONCLUSION:
Acantholytic dyskeratotic acanthomas are clinically and pathologically distinct
lesions, which may morphologically present as either truncal plaques or subungual
longitudinal erythronychia.
PMID- 25126454
TI - Actinic granuloma.
PMID- 25126452
TI - The dermatoscopic universe of basal cell carcinoma.
AB - Following the first descriptions of the dermatoscopic pattern of basal cell
carcinoma (BCC) that go back to the very early years of dermatoscopy, the list of
dermatoscopic criteria associated with BCC has been several times updated and
renewed. Up to date, dermatoscopy has been shown to enhance BCC detection, by
facilitating its discrimination from other skin tumors and inflammatory skin
diseases. Furthermore, upcoming evidence suggests that the method is also useful
for the management of the tumor, since it provides valuable information about the
histopathologic subtype, the presence of clinically undetectable pigmentation,
the expansion of the tumor beyond clinically visible margins and the response to
non-ablative treatments. In the current article, we provide a summary of the
traditional and latest knowledge on the value of dermatoscopy for the diagnosis
and management of BCC.
PMID- 25126455
TI - Is aggressive digital papillary adenocarcinoma really aggressive digital
papillary adenocarcinoma?
PMID- 25126457
TI - Multiple primary thick melanomas: similar dermoscopic pattern.
PMID- 25126456
TI - Keratoacanthoma versus invasive squamous cell carcinoma: a comparison of
dermatoscopic vascular features in 510 cases.
AB - INTRODUCTION: Keratoacanthoma (KA) and invasive squamous cell carcinoma (SCC) are
keratinocytic tumors displaying vascular features, imaged using dermatoscopy.
OBJECTIVE: Compare the dermatoscopy vascular features of KA to SCC. METHODS: This
prospective study examined consecutive cases of 100 KA and 410 invasive SCC in a
single private practice in Sydney, Australia. Vascular features were recorded in
vivo direct from patients using a non-polarized Delta 20 Heine dermatoscope.
These vascular features were: linear, branching, serpentine, hairpin, glomerular
and dot vessels, the presence or absence of large diameter tumor vessels, vessel
presence in central verses peripheral tumor areas and tumor pink areas in
different proportions. Following full excision, all cases were submitted for
histopathologic diagnosis. RESULTS: Branching vessels were the only vessel
morphology that varied, with a significant incidence in KA (25.0%), compared to
SCC (10.7%), P < 0.01. Large vessels were identified in 20.0% of KA, compared to
12.4% in SCC, P = 0.05. No vessels were observed in the central tumor areas in
43.4 % of KA compared to 58.0% of SCC, P = 0.01. Other data comparing the central
versus peripheral tumor areas for vessels present did not reveal any distinctive
associations. There were no significant differences between KA and SCC when
reviewing the selected proportions of pink within the tumor. LIMITATIONS: The
vascular features may be confounded by tumor depth in KA. Polarized dermatoscopy
may not produce the same findings. CONCLUSION: This study found branching vessels
to have a higher incidence in KA compared to invasive SCC. Although not
statistically significant, large diameter vessels were also more frequent in KA.
Proportions of pink within the tumor or central verses peripheral tumor vessel
distribution were not useful diagnostic features separating KA from SCC using
dermatoscopy.
PMID- 25126458
TI - Dermatoscopy of folliculosebaceous cystic hamartoma.
AB - A 29-year-old Japanese man presented to our institution with a nodule on his nose
that had increased in size since childhood. Physical examination indicated the
presence of an elastic, firm, pedunculated red nodule measuring 15 mm in size.
Dermatoscopic examination of the nodule indicated a yellowish-white network,
yellowish-orange dots/globules at its center, and a pinkish-white structureless
peripheral area. Histopathological examination of an excisional biopsy specimen
showed a dilated infundibulocystic structure with sebaceous lobules proliferating
radially, surrounded by fibrous stroma. Moreover, mature adipocytes and small
vessels were noted in the stroma. Based on these histopatho-logic findings, the
patient was diagnosed with folliculosebaceous cystic hamartoma.
PMID- 25126459
TI - Infundibulocystic basal cell carcinoma: dermoscopic findings and histologic
correlation.
AB - Infundibulocystic basal cell carcinoma is a rare variant. It was first described
in 1987 and proposed as a new basal cell carcinoma (BCC) subtype by Ackerman and
Walsh in 1990. Dermoscopy is a noninvasive diagnostic technique that allows
prompt identification of many types of BCC. However, dermoscopic findings for the
infundibulocystic variant have not been reported. In our patient the dermoscopic
findings were maple leaf-like areas in the periphery of the tumor, multiple
scattered blue-gray dots and globules, short, fine telangiectasia and chrysalis
or white-shiny streaks. All these structures had an underlying
anatomopathological correlation. CONCLUSION: According to our case report,
dermoscopy findings may aid to clearly diagnose this unusual BCC variant with
proper histopathological correlation.
PMID- 25126460
TI - Zosteriform cutaneous leishmaniasis diagnosed with the help of dermoscopy.
AB - Cutaneous leishmaniasis is usually easy to recognize; however, several atypical
features exist, which may pose a diagnostic challenge. Here we report a 55-year
old female patient, who presented with an itchy and painful eruption localized in
a dermatomal distribution along the right upper chest. Although the clinical
appearance of the lesions suggested the diagnosis of herpes zoster, dermoscopic
evaluation revealed erythema, hyperkeratosis, burst star whitish appearance and
hairpin vessels, compatible with the diagnosis of cutaneous leishmaniasis.
Indeed, leishmania amastigotes were detected by smear from the lesions.
Zosteriform presentation of cutaneous leishmaniasis, as exemplified by our
patient, is especially rare. In our case dermoscopy has proven to be an
accessible and easy tool to diagnose such atypical presentation of cutaneous
leishmaniasis, and dermatologists in endemic areas should be familiar with its
typical dermoscopic features.
PMID- 25126461
TI - The dermoscopic variability of Degos disease at different stages of progression.
PMID- 25126462
TI - Melanoma and satellite blue papule.
AB - The colors that are seen in dermoscopy depend on the anatomic level of the skin
at which the chromophores are seen. Blue color can be found in a variety of
melanocytic and nonmelanocytic lesions. An 89-year-old man presented with a 3
year history of a slow-growing, hyperpigmented patch located on the distal third
of the right arm. Dermoscopy showed an atypical network, irregularly distributed
globules, pigmented internal streaks and a milky-red area. Based on these
findings a diagnosis of slow-growing malignant melanoma was made. Simultaneously,
a well-defined blue papule was seen on the proximal third of the same arm.
Dermoscopy disclosed a homogeneous blue pattern. After clinical and dermoscopic
correlation our differential diagnosis for this blue lesion included cutaneous
melanoma metastasis, blue nevus and foreign body reaction. The patient recalled
its onset 75 years ago after a grenade explosion. We also discuss the blue lesion
appearance under reflectance confocal microscopy and high-definition optical
coherence tomography. Histopathological examination after excision of the
hyperpigmented patch and blue papule revealed a melanoma in situ and a foreign
body reaction, respectively. The diagnostic evaluation of a blue lesion should
always rely on the integration of all data, especially clinical and dermoscopic
features. Other non-invasive techniques, like reflectance confocal microscopy and
high-definition optical coherence tomography can also be important aids for its
differential diagnosis.
PMID- 25126463
TI - Recognizing the benefits and pitfalls of reflectance confocal microscopy in
melanoma diagnosis.
PMID- 25126464
TI - Dermatoscopy: A multicolored lesion on the forehead.
PMID- 25126465
TI - An atypical pigmented lesion-Answer.
PMID- 25126466
TI - Application of black salve to a thin melanoma that subsequently progressed to
metastatic melanoma: a case study.
AB - This is a case study of a female patient diagnosed with superficial spreading
melanoma who decided to treat the lesion by the application of a preparation
known as black salve. Persistence of the melanoma was documented five years later
with subsequent evidence of metastatic spread to the regional lymph nodes, lungs,
liver, subcutaneous tissues and musculature. A literature search has revealed one
other case study of the use of black salve for the treatment of melanoma.
PMID- 25126467
TI - "Neglected nipples": acanthosis nigricans-like plaques caused by avoidance of
nipple cleansing.
AB - BACKGROUND: Acanthosis nigricans (AN) develops sporadically or in association
with obesity, insulin-resistance and dark pigmentary phenotype. Unusual clinical
presentations of AN may be diagnostically vexing. OBJECTIVES: The aim of the
report is to present unusual clinical and dermoscopic pictures of hyper
keratotic, brownish lesions of the nipples resembling acanthosis nigricans.
PATIENTS/METHODS: Data including clinical and dermoscopic features of two
patients with the "neglected nipples": acanthosis nigricans-like (AN-like)
hyperpigmented plaques caused by avoidance of nipple cleansing. RESULTS: Beside
the anamnestic clue, presentation of AN-like plaques in the "neglected nipples"
is limited to the breasts, in the absence of involvement of other flexural sites
classically affected by AN. Dermoscopy aids the exclusion of a tumor, as it
reveals exclusively structureless, brown-gray-black hyperkeratosis in the absence
of criteria associated with melanocytic or non-melanocytic skin neoplasms of the
nipple. The "neglected breasts" are easily treated by keratolytic creams and
hygiene. CONCLUSIONS: The "neglected nipples" condition, presenting as bilateral
AN-like papules and plaques of the nipples, is due to avoidance of cleansing of
the nipple area, resulting in accumulation of keratotic cellular debris.
PMID- 25126468
TI - A dermoscope allowing the use of surgical light as illumination.
PMID- 25126469
TI - Cutis marmorata telangiectatica congenita restricted to both breasts in a young
female.
AB - Cutis marmorata telangiectatica congenita (CMTC) is a very rarely occurring
congenital disorder with persistent cutis marmorata, telangiectasia, and
phlebectasia. This disorder may be associated with cutaneous atrophy and
ulceration of the involved skin. We herewith report a 20-year-old female patient
with CMTC since childhood along with ulcerations on both breasts. CMTC is a
benign vascular anomaly presenting with dilatation of capillaries and veins of
dermis and is apparent at birth. The patient had reticulated bluish-purple skin
changes over both breasts. Although it resembled physiological cutis marmorata,
it was more pronounced and definitely was unvarying and permanent in pattern. A
variety of vascular malformations have been described along with this disorder.
Etiology is not very clear; it may be multifactorial in origin. Prognosis in
uncomplicated cases is good.
PMID- 25126470
TI - Uncommon presentations of tinea versicolor.
AB - Tinea versicolor (TV) is a common cutaneous fungal infection characterized by
superficial scaling and a mild disturbance of skin pigmentation. It typically
affects the chest, upper back, and shoulders. However, involvement of more
unusual regions of the body such as the face and scalp, arms and legs,
intertriginous sites, genitalia, areolae, and palms and soles has been reported.
This report details two such cases observed at our institution: a 32-year-old
woman with involvement of the popliteal fossa and a 16-year-old boy with
involvement of the groin. The clinician must be aware of these variations in
location and perform the appropriate diagnostic workup when lesions have the
characteristic morphology of TV despite an unusual location. The etiology,
pathophysiology, and epidemiology of TV are reviewed and current literature
describing other instances of TV in uncommon locations is discussed.
PMID- 25126471
TI - Letter to the editor.
PMID- 25126473
TI - The Topical Evolution: Free Ions, Orthomolecular Agents, Phytochemicals, and
Insect-Produced Substances.
AB - Significance: A variety of topical antiseptic substances have been used
historically to treat open wounds with suspected tissue infection or that are
slow to heal. However, the effectiveness of these substances in treating infected
or recalcitrant wounds remains controversial. Recent Advances: Newly formulated
topical antiseptics delivered through differing dressing technologies, such as
ionic substances, hold the potential to limit the development of and treat
antibiotic-resistant microbes in open wounds. Other topically delivered
substances, such as insect-derived substances, orthomolecular agents, and
phytochemicals, also present opportunities to optimize wound healing by
decreasing tissue bioburden and facilitating the wound healing process. Critical
Issues: Limited systemic perfusion of open wounds in individuals with certain
diagnoses, such as peripheral arterial disease or necrotizing infection and the
increasing number of antibiotic-resistant wound pathogens, suggests a continued
role for topically applied antiseptic agents. Likewise, the failure of wounds to
heal when treated with standard of care therapy opens the door to innovative
treatment approaches that include the natural substances described in this
article. Future Directions: Evidence for the use of select topical antiseptic
agents from each of the aforementioned categories will be discussed in this
article. Additional well-controlled clinical studies are needed to provide
definitive recommendations for many of these topical agents.
PMID- 25126474
TI - What Do Patients Want? Patient Preference in Wound Care.
AB - Patient preferences are statements made or actions taken by consumers that
reflect their desirability of a range of health options. The concept occupies an
increasingly prominent place at the center of healthcare reform, and is connected
to all aspects of healthcare, including discovery, research, delivery, outcome,
and payment. Patient preference research has focused on shared decisions,
decisional aids, and clinical practice guideline development, with limited study
in acute and chronic wound care populations. The wound care community has focused
primarily on patient focused symptoms and quality of life measurement. With
increasing recognition of wound care as a medical specialty and as a public
health concern that consumes extensive resources, attention to the preferences of
end-users with wounds is necessary. This article will provide an overview of
related patient-centered concepts and begin to establish a framework for
consideration of patient preference in wound care.
PMID- 25126475
TI - Collect Data, Tell Stories: Utilizing Available Data to Improve Wound Product
Selection, Reduce Costs, and Improve Outcomes.
AB - Objective: To develop a tool to assist in the evaluation of treatment options
based on clinically relevant parameters, thus enabling clinicians to heal
patients more efficiently. Approach: Outlined here is the prototypic model of a
comprehensive analysis tool to compare products by category, accounting for
product characteristics, effectiveness data from literature, costs, and patient
needs or clinician preferences. Results: The tool is demonstrated with a venous
leg ulcer example, and ideas for expanding the tool in the future are provided.
Innovation: Although this is a simple model, the authors believe that it provides
a valid and useful platform for comparing similar products of a given type using
available information and reflecting real-world use to give a practical approach
to clinical decision-making. Conclusion: Future funding for comprehensive,
comparative effectiveness studies should provide clarity on which products to
choose for specific applications. Meanwhile, tools like this can provide
guidance, and can be modified to accommodate varying circumstances.
PMID- 25126476
TI - A Global Perspective on Wound Care.
AB - The development of an interprofessional team approach to the care of acute and
chronic wounds is a worldwide challenge. This global unmet need has recently been
recognized by the World Health Organization (WHO) and addressed by the
Association for the Advancement of Wound Care (AAWC) Global Volunteers program.
This article provides an overview of the escalating international wound problem.
Current programs established to deal with wounds in resource-poor countries are
presented as well as information on volunteering.
PMID- 25126472
TI - Wound Dressings and Comparative Effectiveness Data.
AB - Significance: Injury to the skin provides a unique challenge, as wound healing is
a complex and intricate process. Acute wounds have the potential to move from the
acute wound to chronic wounds, requiring the physician to have a thorough
understanding of outside interventions to bring these wounds back into the
healing cascade. Recent Advances: The development of new and effective
interventions in wound care remains an area of intense research. Negative
pressure wound therapy has undoubtedly changed wound care from this point forward
and has proven beneficial for a variety of wounds. Hydroconductive dressings are
another category that is emerging with studies underway. Other modalities such as
hyperbaric oxygen, growth factors, biologic dressings, skin substitutes, and
regenerative materials have also proven efficacious in advancing the wound
healing process through a variety of mechanisms. Critical Issues: There is an
overwhelming amount of wound dressings available in the market. This implies the
lack of full understanding of wound care and management. The point of using
advanced dressings is to improve upon specific wound characteristics to bring it
as close to "ideal" as possible. It is only after properly assessing the wound
characteristics and obtaining knowledge about available products that the "ideal"
dressing may be chosen. Future Directions: The future of wound healing at this
point remains unknown. Few high-quality, randomized controlled trials evaluating
wound dressings exist and do not clearly demonstrate superiority of many
materials or categories. Comparative effectiveness research can be used as a tool
to evaluate topical therapy for wound care moving into the future. Until further
data emerge, education on the available products and logical clinical thought
must prevail.
PMID- 25126477
TI - Medicare Payment: Surgical Dressings and Topical Wound Care Products.
AB - Medicare patients' access to surgical dressings and topical wound care products
is greatly influenced by the Medicare payment system that exists in each site of
care. Qualified healthcare professionals should consider these payment systems,
as well as the medical necessity for surgical dressings and topical wound care
products. Scientists and manufacturers should also consider these payment
systems, in addition to the Food and Drug Administration requirements for
clearance or approval, when they are developing new surgical dressings and
topical wound care products. Due to the importance of the Medicare payment
systems, this article reviews the Medicare payment systems in acute care
hospitals, long-term acute care hospitals, skilled nursing facilities, home
health agencies, durable medical equipment suppliers, hospital-based outpatient
wound care departments, and qualified healthcare professional offices.
PMID- 25126478
TI - Preconditioning stem cells for in vivo delivery.
AB - Stem cells have emerged as promising tools for the treatment of incurable neural
and heart diseases and tissue damage. However, the survival of transplanted stem
cells is reported to be low, reducing their therapeutic effects. The major causes
of poor survival of stem cells in vivo are linked to anoikis, potential immune
rejection, and oxidative damage mediating apoptosis. This review investigates
novel methods and potential molecular mechanisms for stem cell preconditioning in
vitro to increase their retention after transplantation in damaged tissues.
Microenvironmental preconditioning (e.g., hypoxia, heat shock, and exposure to
oxidative stress), aggregate formation, and hydrogel encapsulation have been
revealed as promising strategies to reduce cell apoptosis in vivo while
maintaining biological functions of the cells. Moreover, this review seeks to
identify methods of optimizing cell dose preparation to enhance stem cell
survival and therapeutic function after transplantation.
PMID- 25126479
TI - Combinatorial fibronectin and laminin signaling promote highly efficient cardiac
differentiation of human embryonic stem cells.
AB - Cardiomyocytes (CMs) differentiated from human embryonic stem cells (hESCs) are a
promising and potentially unlimited cell source for myocardial repair and
regeneration. Recently, multiple methodologies-primarily based on the
optimization of growth factors-have been described for efficient cardiac
differentiation of hESCs. However, the role of extracellular matrix (ECM)
signaling in CM differentiation has not yet been explored fully. This study
examined the role of ECM signaling in the efficient generation of CMs from both
H7 and H9 ESCs. The hESCs were differentiated on ECM substrates composed of a
range of fibronectin (FN) and laminin (LN) ratios and gelatin and evaluated by
the fluorescence activated cell scanning (FACS) analysis on day 14. Of the ECM
substrates examined, the 70:30 FN:LN reproducibly generated the greatest numbers
of CMs from both hESC lines. Moreover, the LN receptor integrin beta4 (ITGB4) and
FN receptor integrin beta5 (ITGB5) genes, jointly with increased phosphorylated
focal adhension kinase and phosphorylated extracellular signal-regulated kinases
(p-ERKs), were up-regulated over 13-fold in H7 and H9 cultured on 70:30 FN:LN
compared with gelatin. Blocking studies confirmed the role of all these molecules
in CM specification, suggesting that the 70:30 FN:LN ECM promotes highly
efficient differentiation of CMs through the integrin-mediated MEK/ERK signaling
pathway. Lastly, the data suggest that FN:LN-induced signaling utilizes direct
cell-to-cell signaling from distinct ITGB4(+) and ITGB5(+) cells.
PMID- 25126480
TI - Directing human induced pluripotent stem cells into a neurosensory lineage for
auditory neuron replacement.
AB - Emerging therapies for sensorineural hearing loss include replacing damaged
auditory neurons (ANs) using stem cells. Ultimately, it is important that these
replacement cells can be patient-matched to avoid immunorejection. As human
induced pluripotent stem cells (hiPSCs) can be obtained directly from the
patient, they offer an opportunity to generate patient-matched neurons for
transplantation. Here, we used an established neural induction protocol to
differentiate two hiPSC lines (iPS1 and iPS2) and one human embryonic stem cell
line (hESC; H9) toward a neurosensory lineage in vitro. Immunocytochemistry and
qRT-PCR were used to analyze the expression of key markers involved in AN
development at defined time points of differentiation. The hiPSC- and hESC
derived neurosensory progenitors expressed the dorsal hindbrain marker (PAX7),
otic placodal marker (PAX2), proneurosensory marker (SOX2), ganglion neuronal
markers (NEUROD1, BRN3A, ISLET1, betaIII-tubulin, Neurofilament kDa 160), and
sensory AN markers (GATA3 and VGLUT1) over the time course examined. The hiPSC-
and hESC-derived neurosensory progenitors had the highest expression levels of
the sensory neural markers at 35 days in vitro. Furthermore, the neurons
generated from this assay were found to be electrically active. While all cell
lines analyzed produced functional neurosensory-like progenitors, variabilities
in the levels of marker expression were observed between hiPSC lines and within
samples of the same cell line, when compared with the hESC controls. Overall,
these findings indicate that this neural assay was capable of differentiating
hiPSCs toward a neurosensory lineage but emphasize the need for improving the
consistency in the differentiation of hiPSCs into the required lineages.
PMID- 25126481
TI - Establishment and characterization of a singaporean chinese lung adenocarcinoma
cell line with four copies of the epidermal growth factor receptor gene.
AB - We have established a lung adenocarcinoma cell line, ETCC016, from lung pleural
effusion of a male Singaporean Chinese with advanced lung adenocarcinoma. The
subject smoked 20 cigarettes per day for more than 30 years. The cell line arose
from spontaneous transformation of cells grown in a collagen-coated culture dish.
Transformed characteristics of the cell line include the ability to reach high
confluency in a culture dish, low cell doubling time, ability to form colonies in
soft agar, and ability to form solid tumor in immune-compromised SCID mice.
Immunostaining showed that the cells originated from lung epithelial cells.
Genomic analysis revealed a large amount of chromosomal aberrations (gain and
loss of genetic materials, and loss of heterozygosity [LOH]), indicative of a
long history of smoking. The cells have four copies of epidermal growth factor
receptor (EGFR) and three copies of MYC, but have lost one copy of the RB1 gene.
LOH was detected in TP53 and BRAF genes. There is no anaplastic lymphoma kinase
(ALK) gene rearrangement. The ETCC016 lung adenocarcinoma cell line has
demonstrated susceptibility towards inhibitors specific for EGFR/HER2 and ALK
targets, but resistance to MYC-specific inhibitor. This cell line will be a
useful model for further understanding of lung adenocarcinoma.
PMID- 25126482
TI - A moderate increase of hydrogen peroxide level is beneficial for spontaneous
resumption of meiosis from diplotene arrest in rat oocytes cultured in vitro.
AB - Hydrogen peroxide (H2O2) acts as a signaling molecule and modulates various
aspects of cell functions in a wide variety of cells including mammalian germ
cells. We examined whether a decreased level of intra-oocyte cyclic 3',5'
adenosine monophosphate (cAMP) leads to accumulation of H2O2, and if so, whether
a moderate increase of H2O2 inactivates maturation promoting factor (MPF) during
spontaneous resumption of meiosis in rat oocytes cultured in vitro. Removal of
cumulus cells and culture of denuded oocytes in vitro significantly decreased
oocyte cAMP level and led to spontaneous meiotic resumption from diplotene
arrest. The reduced oocyte cAMP level was associated with an increased oocyte
H2O2 level and reduced catalase activity. Exogenous supplementation of H2O2
induced meiotic resumption from diplotene arrest in a concentration- and time
dependent manner in oocytes treated with 0.1 mM of 3-isobutyl-1-methylxanthine,
while dibutyryl-cAMP and 3-t-butyl-4-hydroxyanisole inhibited the stimulatory
effect of exogenous H2O2. The increased intra-oocyte H2O2 level induced Thr
14/Tyr-15 phosphorylation of CDK1, while Thr-161 phosphorylated CDK1 and cyclin
B1 levels were reduced significantly. These results suggest that a decreased
level of intra-oocyte cAMP is associated with an increased level of H2O2. The
increased level of H2O2 was associated with high phosphorylation of Thr-14/Tyr-15
and dephosphorylation of the Thr-161 residue of CDK1 and reduced the cyclin B1
level, which eventually inactivated MPF. The MPF inactivation triggered
spontaneous resumption of meiosis from diplotene arrest in rat oocytes cultured
in vitro.
PMID- 25126483
TI - High resolution x-ray: a reliable approach for quantifying osteoporosis in a
rodent model.
AB - Osteoporosis is the most common metabolic disease of bone, resulting in
significant worldwide morbidity. Currently, there are insufficient imaging
modalities available to evaluate osteoporotic bones in small animal models. Here,
we demonstrate the feasibility of using high resolution X-ray imaging as a
comparable measure of bone degeneration to dual-energy X-ray absorptiometry (DXA)
in an osteoporosis rodent model. At week 0, animals underwent either an
ovariectomy (OVX) or sham procedure (SHAM). DXA analysis was performed weekly to
confirm and compare the bone degenerative changes induced by OVX. A comparison
using high resolution X-ray imaging (Faxitron((r))) was then performed postmortem
due to need of soft tissue removal. Two regions of interest (ROIs) were utilized:
the distal third of the femur and the lumbar spine (L4/L5). It was observed that
SHAM animals maintained a relatively constant bone mineral density (BMD), in
comparison to OVX animals, whereby a significant decrease in BMD was appreciated.
Post mortem X-ray scans were performed and converted to 8-bit color and
quantified. A high level of agreement with DXA quantifications was observed with
X-ray quantifications, and a significant correlation between the radiopacity,
visualized by color distributions, and the DXA BMD values between animal groups
was evident. Our study demonstrates the applicability of high resolution X-ray
imaging both qualitatively and quantitatively as a reliable approach for
quantifying osteoporosis in rodent osteoporotic models. With DXA being a highly
user dependent modality, our technique is a unique secondary methodology to
verify DXA findings and minimize inter-observer variability.
PMID- 25126484
TI - Prosthetic valve endocarditis due to Streptococcus pneumoniae.
AB - INTRODUCTION: In the pre-antibiotic era up 10% of cases of infective endocarditis
were due to Streptococcus pneumoniae, but this association is currently
exceedingly rare. CASE DESCRIPTION: Since 1997 we have diagnosed three patients,
all aged >70, with endocarditis due to S. pneumoniae. One of these three cases
involved a prosthetic valve, another a prosthetic ring. All three patients
completely recovered with antibiotic treatment only. DISCUSSION AND EVALUATION:
During the same period there were 1694 cases of pneumococcal bacteremia, of whom
395 (23%) after age 70. Therefore, after age 70 the prevalence of endocarditis
out of all cases of pneumococcal bacteremia was 0.7%. A literature review
detected another 16 cases of pneumococcal PVE. The mean age of these 17 patients
was 64+/-14; 10 were female and 7 male. In most instances, symptom duration was
short, < 6 days. Valve surgery was performed in 5 cases (29%) and 13 patients
(76%) survived. CONCLUSIONS: Endocarditis due to S. pneumoniae is rare in the
antibiotic era; even in patients with prosthetic valves its course is evidently
not more virulent than with other low-virulent organisms.
PMID- 25126485
TI - The association in a two-way contingency table through log odds ratio analysis:
the case of Sarno river pollution.
AB - In this paper we are proposing a general framework for the analysis of the
complete set of log Odds Ratios (ORs) generated by a two-way contingency table.
Starting from the RC (M) association model and hypothesizing a Poisson
distribution for the counts of the two-way contingency table we are obtaining the
weighted Log Ratio Analysis that we are extending to the study of log ORs.
Particularly we are obtaining an indirect representation of the log ORs and some
synthesis measures. Then for studying the matrix of log ORs we are performing a
generalized Singular Value Decomposition that allows us to obtain a direct
representation of log ORs. We also expect to get summary measures of association
too. We have considered the matrix of complete set of ORs, because, it is linked
to the two-way contingency table in terms of variance and it allows us to
represent all the ORs on a factorial plan. Finally, a two-way contingency table,
which crosses pollution of the Sarno river and sampling points, is to be analyzed
to illustrate the proposed framework.
PMID- 25126486
TI - Genetic fragmentation in India's third longest river system, the Narmada.
AB - India's third longest river, the Narmada, is studied here for the potential
effects on native fish populations of river fragmentation due to various barriers
including dams and a waterfall. The species we studied include a cyprinid fish,
Catla catla, and a mastacembelid, Mastacembelus armatus, both of which are found
in the Narmada. Our goal was to use DNA sequence information from the D-loop
region of the mitochondrial DNA to explore how this fragmentation could impact
the genetic structure of these fish populations. Our results clearly show that
these barriers can contribute to the fragmentation of the genetic structure of
these fish communities, Furthermore, these barriers enhance the effects of
natural isolation by distance and the asymmetry of dispersal flows. This may be a
slow process, but it can create significant isolation and result in genetic
disparity. In particular, populations furthest upstream having low migration
rates could be even more subject to genetic impoverishment. This study serves as
a first report of its kind for a river system on the Indian subcontinent. The
results of this study also emphasize the need for appropriate attention towards
the creation of fish passages across the dams and weirs that could help in
maintaining biodiversity.
PMID- 25126488
TI - Rare aggressive natural killer cell leukemia presented with bone marrow fibrosis
a diagnostic challenge.
AB - Aggressive natural killer cell leukemia is an extraordinary rare aggressive
malignant neoplasm of natural killer cells. Although its first recognition as a
specific entity was approximately 20 years ago, this leukemia has not yet been
satisfactorily characterized as fewer than 200 cases have been reported in the
literature and up to our knowledge, this is the first case report in Qatar.
Reaching a diagnosis of aggressive natural killer leukemia was a challenging
experience, because in addition to being a rare entity, the relative scarcity of
circulating neoplastic cells, failure to obtain an adequate aspirate sample
sufficient to perform flow cytometric analysis, together with the absence of
applicable method to prove NK clonality (as it lack specific clonal marker); our
case had atypical confusing presentation of striking increase in bone marrow
fibrosis that was misleading and complicated the case further. The bone marrow
fibrosis encountered may be related to the neoplastic natural killer cells'
chemokine profile and it may raise the awareness for considering aggressive
natural killer leukemia within the differential diagnosis of leukemia with
heightened marrow fibrosis.
PMID- 25126487
TI - Evaluation of industrial dairy waste (milk dust powder) for acetone-butanol
ethanol production by solventogenic Clostridium species.
AB - Readily available inexpensive substrate with high product yield is the key to
restoring acetone-butanol-ethanol (ABE) fermentation to economic competitiveness.
Lactose-replete cheese whey tends to favor the production of butanol over
acetone. In the current study, we investigated the fermentability of milk dust
powder with high lactose content, for ABE production by Clostridium
acetobutylicum and Clostridium beijerinckii. Both microorganisms produced 7.3 and
5.8 g/L of butanol respectively, with total ABE concentrations of 10.3 and 8.2
g/L, respectively. Compared to fermentation with glucose, fermentation of milk
dust powder increased butanol to acetone ratio by 16% and 36% for C.
acetobutylicum and C. beijerinckii, respectively. While these results demonstrate
the fermentability of milk dust powder, the physico-chemical properties of milk
dust powder appeared to limit sugar utilization, growth and ABE production.
Further work aimed at improving the texture of milk dust powder-based medium
would likely improve lactose utilization and ABE production.
PMID- 25126489
TI - Expressive aphasia in a patient with chronic myelomonocytic leukemia.
AB - Various paraneoplastic autoimmune phenomena have been reported in patients with
myelodysplastic syndromes. We describe a patient who developed expressive aphasia
as a paraneoplastic complication of chronic myelomonocytic leukemia (CMML).
Awareness of the various possible manifestations of CMML may aid in the early
recognition of the condition.
PMID- 25126490
TI - Non-high-density lipoprotein cholesterol (non-HDL-C) levels in children with
nonalcoholic fatty liver disease (NAFLD).
AB - Non-alcoholic fatty liver disease (NAFLD) is associated with increased
cardiovascular disease (CVD) risk in children. Non-high density lipoprotein
cholesterol (non-HDL-C) has been shown to be a good predictor of cardiovascular
events. Recent data in adults found non-alcoholic steatohepatitis (NASH) to be
associated with significantly higher levels of non-HDL-C than simple steatosis,
suggestive it might be used as a non-invasive tool to diagnose NASH. The goal of
our study was to assess non-HDL-C levels in children with NAFLD. Our cohort
consisted of pediatric patients with biopsy-proven NAFLD. Anthropometric,
laboratory, and histologic data were obtained on all patients. Univariable
analysis was performed to assess differences in clinical characteristics between
groups. Spearman rank correlation coefficients were calculated to assess the
correlation between non-HDL-C levels and clinical variables. ANCOVA was used to
adjust for possible confounders. 302 subjects with NAFLD were included in our
study; 203 with NASH and 99 without NASH. Subjects with NASH had significantly
higher non-HDL-C levels than those without (p = 0.004). Histologic features of
NASH, including ballooning, inflammation, and fibrosis were found to be weakly
correlated with non-HDL-C levels, (p < 0.05 for all). After adjusting for the
presence of metabolic syndrome (MetS), ALT, and GGT, the association between non
HDL-C and NASH was not significant (p = 0.66). In Conclusion, non-HDL-C levels
are higher in children with NASH than those with simple steatosis, suggesting
increased CVD risk. This may be a reflection of the higher prevalence of MetS.
Non-HDL-C had a positive association with histologic features of NASH.
PMID- 25126491
TI - Personalized medicine approach in mycobacterial disease.
AB - Mycobacterial diseases are a group of illnesses that cause a considerable number
of deaths throughout the world, regardless of years of public health control
efforts. Personalized medicine is a new but rapidly advancing field of
healthcare. Personalized medicine in the field of mycobacteriology may be applied
in the different levels of management such as prevention, diagnosis, treatment
and prognosis. A genetic predisposition and a protein dysfunction study are
recommended to tailor an individual approach in mycobacterial diseases.
PMID- 25126492
TI - Arthroscopically confirmed femoral button deployment.
AB - The anterior cruciate ligament TightRope RT (Arthrex, Naples, FL) is a graft
suspension device for cruciate ligament reconstruction. It is an adjustable
length graft loop cortical fixation device designed to eliminate the requirement
for loop length calculation and to facilitate complete graft fill of short
femoral sockets that are common with anatomic anterior cruciate ligament
placement. The adjustable loop length means "one size fits all," thus removing
the need for multiple implant sizes and allowing graft tensioning even after
fixation. However, the device has been associated with the same complications
that have been described with EndoButton (Smith & Nephew Endoscopy, Andover, MA)
fixation. The button of the TightRope RT may remain in the femoral tunnel rather
than flipping outside of the tunnel to rest on the lateral femoral cortex, or it
may become jammed inside the femoral canal. Conversely, the button may be pulled
too far off the femoral cortex into the overlying soft tissue and flip in the
substance of the vastus lateralis. We describe a new and simple arthroscopic
technique to directly visualize the deployment and seating of the TightRope
button on the lateral cortex of the femur to avoid all the aforementioned
complications.
PMID- 25126493
TI - An augmentation suture technique for arthroscopic rotator cuff repair.
AB - The double-row suture technique and the suture-bridge technique have been used
for rotator cuff repair to decrease the occurrence of retears. However, when only
the degenerated tendon end is sutured, the risk of retear remains. The
augmentation suture technique is a new procedure that connects the intact medial
tendon to the lateral greater tuberosity, and this approach may protect the
initial repair site. The procedures for this technique are as follows: 2 sutures
are placed through the medial intact tendon, the cuff tear is repaired by the
single-row technique, 2 sutures are pulled laterally over the single-row repair
site, and 2 sutures are fixed at the lateral greater tuberosity with a push-in
type anchor. This technique is simple and easy and does not require special
equipment. Moreover, this approach can augment the single-row repair technique
without creating high tension at the cuff end.
PMID- 25126494
TI - Retrograde synovial biopsy of the knee joint using a novel biopsy forceps.
AB - Synovial biopsies of the knee joint are commonly performed arthroscopically with
the patient under full or regional anesthesia. To overcome the effort, costs, and
potential risks of surgery, we developed an office-based technique for retrograde
synovial biopsy using a designated novel biopsy forceps. Using this technique, no
arthroscopic or radiologic control is needed to perform rapid synovial biopsies
of the knee joint. Concomitant aspiration of synovial fluid can be performed. A
technical description of the procedure is given.
PMID- 25126495
TI - Hamstring graft preparation using a modified rolling hitch technique.
AB - Anterior cruciate ligament reconstruction using double-looped hamstring autograft
is a common procedure in orthopaedic practice. However, during placement of the
running, locking stitches at each end of the harvested tendons, the surgeon may
face several potential obstacles, including the risk of damaging the tendon,
predisposing the surgeon to needle-stick injury, and extended time consumption.
We report a modified rolling hitch technique for hamstring graft preparation that
is quick, cost-saving, and needleless as an alternative method. The original
rolling hitch technique uses a traditional knot that attaches a rope to an
object; the modified rolling hitch technique was created by adding 1 more turn
before finishing with a half-hitch, which may prevent suture slippage off the
tendon, thus providing sufficient fixation of the suture-tendon construct.
PMID- 25126496
TI - Minimally invasive reconstruction of the medial patellofemoral ligament using
quadriceps tendon.
AB - Reconstruction of the medial patellofemoral ligament (MPFL) for the treatment of
patellar instability has received increased attention over the past few years.
Most operative techniques use hamstring grafts fixed with bone tunnels and/or
anchors on the patella. Despite good clinical results using these techniques,
complications such as implant breakage, patellar fractures through bone tunnels,
and loss of knee motion have occurred. We present a minimally invasive technique
for MPFL reconstruction using a strip of quadriceps tendon. With the use of
specially designed instruments, the graft is harvested through a 3-cm transverse
incision at the proximal pole of the patella. The tendon strip is then dissected
distally on the patella, left attached, and diverged 90 degrees medially
underneath the medial prepatellar tissue. The graft is fixed on the femur in 20
degrees of knee flexion in a bone tunnel with a bioabsorbable interference screw
(adults) or a bone anchor (children). We think that this technique presents a
valuable alternative to common hamstring techniques for primary MPFL
reconstruction in children and adults, as well as for MPFL revision surgery.
PMID- 25126497
TI - Arthroscopic excision of bone fragments in a neglected fracture of the lateral
process of the talus in a junior soccer player.
AB - Fractures of the lateral process of the talus are uncommon and often overlooked.
Typically, they are found in adult snowboarders. We report the case of an 11-year
old male soccer player who complained of lateral ankle pain after an inversion
injury 6 months earlier. He did not respond to conservative treatment and thus
underwent arthroscopic excision of fragments of the talar lateral process. The
ankle was approached through standard medial and anterolateral portals. A 2.7-mm
diameter 30 degrees arthroscope was used. Soft tissues around the talus were
cleared with a motorized shaver, and the lateral aspect of the talar process was
then visualized. The lateral process presented as an osseous overgrowth, and a
loose body was impinged between the talus and the calcaneus. The osseous
overgrowth was resected piece by piece with a punch, and the loose body was
removed en block. The patient returned to soccer 5 weeks after the operation.
This case exemplifies 2 important points: (1) This type of fracture can develop
even in children and not only in snowboarders. (2) Arthroscopic excision of talar
lateral process fragments can be accomplished easily, and return to sports can be
achieved in a relatively short time.
PMID- 25126498
TI - Pediatric anterior cruciate ligament femoral fixation: the trans-iliotibial band
endoscopic portal for direct visualization of ideal button placement.
AB - Pediatric and adolescent anterior cruciate ligament reconstruction is a commonly
performed procedure that has been increasing in incidence. Multiple techniques
for graft fixation have been described. Button-based femoral cortical suspension
fixation of the anterior cruciate ligament graft allows for fast, secure fixation
with strong load-to-failure biomechanical properties. The biomechanical
properties of button-based femoral cortical suspension fixation are especially
beneficial with soft-tissue grafts such as hamstring autografts. Confirmation of
a successfully flipped button can be achieved with intraoperative fluoroscopy or
indirect viewing; however, these techniques do not provide direct visualization
of the flipped button. Our trans-iliotibial band endoscopic portal allows the
surgeon to safely and directly visualize the flipped button on the lateral
femoral cortex and ensure that there is no malpositioning in the form of an
incompletely flipped button or from soft-tissue interposition between the button
and the lateral femoral cortex. This portal therefore allows for direct visual
confirmation that the button is fully flipped and resting flush against the
femoral cortex, deep to the iliotibial band and vastus lateralis.
PMID- 25126499
TI - Arthroscopic delivery of cancellous tibial autograft for unstable osteochondral
lesions in the adolescent knee.
AB - The appropriate surgical technique for the treatment of unstable osteochondral
lesions of the knee remains unclear and had been traditionally described with an
open arthrotomy. Administration of bone grafting material in the knee may be
performed for a variety of pathologic conditions, including unstable
osteochondritis dissecans, traumatic osteochondral defects, or subchondral
fracture nonunion, or for preparation of residual tunnels during revision
anterior cruciate ligament reconstruction. Although various grafting materials
have been described in the literature, cancellous autograft remains the gold
standard for treatment safety and efficacy. We describe a successful technique
for arthroscopic delivery of autogenous bone graft during fixation of unstable
osteochondral lesions of the knee. When the indication for grafting is
established, cancellous autograft is harvested from the proximal tibia, undergoes
morcellation, and is soaked in bone marrow aspirate obtained through the harvest
window. The bone graft is then packed into a modified tuberculin syringe. After
arthroscopic preparation of the unstable osteochondral fragment and the
respective donor surface, the tuberculin syringe is placed through a standard
arthroscopy portal and the bone graft is introduced into the defect under direct
visualization, followed by an appropriate osteochondral fixation technique.
PMID- 25126500
TI - The golf ball sign: arthroscopic localization of an osteochondritis dissecans
lesion of the knee.
AB - We report on the arthroscopic treatment of a 12-year-old boy diagnosed with an
osteochondral defect of the medial femoral condyle. He underwent arthroscopic
fixation of the defect, and during the surgery, a blunt trocar was used to
localize the lesion. The trocar created a transient dimpling effect on the
cartilage overlying the osteochondral defect that resembled the surface of a golf
ball. This "golf ball sign" then served as a visual guide during placement of a
chondral dart. When present, it is believed that this sign can benefit
arthroscopists by helping to improve intraoperative localization of an
osteochondral defect.
PMID- 25126501
TI - Arthroscopic Resection of Intra-Articular Osteochondromas of the Hip.
AB - Proximal femur osteochondromas are relatively rare, particularly in the femoral
neck. The choice of treatment poses difficulties to the surgeon. We report an
unusual case of a patient with 2 osteochondromas in the femoral neck causing
femoroacetabular impingement. Appropriate identification and precise resection of
the lesions are important steps of the surgical procedure. We present our
arthroscopic surgical technique to access the lesions and perform their
resection. To our knowledge, this is the first report of hip arthroscopic
resection of 2 osteochondromas with considerable dimensions causing
femoroacetabular impingement.
PMID- 25126502
TI - Arthroscopic hip labral repair: the iberian suture technique.
AB - Arthroscopic hip labral repair has beneficial short-term outcomes; however,
debate exists regarding ideal surgical labral repair technique. This technical
note presents an arthroscopic repair technique that uses intrasubstance labral
suture passage to restore the chondrolabral interface. This "Iberian suture
technique" allows for an anatomic repair while posing minimal risk of damage to
the labral and chondral tissues.
PMID- 25126503
TI - Arthroscopic labral reconstruction of the hip using local capsular autograft.
AB - Labral reconstruction is becoming an important treatment modality for hips with
nonsalvageable labra. Nonsalvageable labra can be present in cases of
intrasubstance damage, revision surgery after debridement, labral calcification,
and hypoplasia. Previous methods of reconstruction have been performed in an open
manner and arthroscopically using ligamentum teres, iliotibial band, and gracilis
autograft. We present an alternate method of arthroscopic labral reconstruction
using capsular autograft. The technique uses readily available capsular tissue
during arthroscopy with no donor-site morbidity. This technique may be valuable
in appropriately selected patients with labral deficiency.
PMID- 25126504
TI - Recycling Suture Limbs from Knotless Suture Anchors for Arthroscopic Shoulder
Stabilization.
AB - Recurrent shoulder instability often leads to labral abnormality that requires
surgical intervention that may require fixation with suture anchors. The proposed
surgical technique allows the surgeon to achieve 2 points of fixation around the
labrum and/or capsule with a single suture secured to the glenoid with a knotless
anchor. Instead of cutting and discarding the residual suture limbs after anchor
insertion, this technique uses the residual suture limbs of the knotless anchor
for a second suture pass. This technique (1) creates a more cost- and time
efficient surgical procedure than using multiple single-loaded anchors or double
loaded anchors, (2) decreases the known risk of glenoid fracture from the stress
riser at the implant tips of multi-anchor repairs by reducing the number of
anchors required for stabilization, (3) decreases the surgical time compared with
the use of double-loaded anchors through simpler suture management and less knot
tying, (4) allows for the secure reapproximation of the labrum to the glenoid
while offering a convenient option for capsulorrhaphy without the need to insert
another anchor, and (5) yields more points of soft-tissue fixation with fewer
anchors drilled into the glenoid.
PMID- 25126505
TI - A new technique for patch augmentation of rotator cuff repairs.
AB - Massive rotator cuff tears defying primary repair have been treated with
debridement, arthroscopic subacromial decompression, partial repair, muscle
tendon transfer, and joint prosthesis, among other techniques. However, the
treatment results have not been satisfactory compared with those of small- to
medium-sized rotator cuff tears; each procedure has its merits and demerits, and
currently, there is no single established method. For massive rotator cuff tears
defying primary repair, the arthroscopic patch graft procedure has been reported
as an effective surgical procedure, and this procedure is chosen as the first
line treatment in our department. In this procedure, suture anchors are generally
used to fix the patch graft to the footprint on the side of the greater
tuberosity. However, tendon-to-bone healing is frequently difficult to achieve,
and bone-to-bone healing seems more advantageous for the repair of the rotator
cuff attachment site. To improve the results of treatment, a new patch graft
procedure was developed, in which the iliotibial ligament with bone was collected
at Gerdy's tubercle and the bone was anchored to the footprint on the side of the
greater tuberosity. With this procedure, excellent results were obtained,
although only short-term results are available at present. The technique and its
results so far are reported.
PMID- 25126506
TI - Arthroscopic technique for the treatment of patellar chondral lesions with the
patient in the supine position.
AB - We describe an arthroscopic approach for the treatment of patellar chondral
lesions with the patient in the supine position. This approach can be used to
perform certain procedures such as matrix autologous chondrocyte implantation and
autologous matrix-induced chondrogenesis. It is possible to perform these
arthroscopic techniques working at an angle perpendicular to the patellar joint
surface. First, with the patient in the supine position, arthroscopic
longitudinal sectioning of the lateral patellar retinaculum is performed, and the
patella is reverted with the help of a Codivilla forceps. It is then possible to
place the chondral surface perpendicular to the floor, and it can be accessed
directly through a lateral parapatellar portal. Short-term follow-up has shown
the benignity of opening the patellar retinaculum. This procedure reduces
morbidity compared with the traditional open surgery.
PMID- 25126507
TI - Arthroscopic Treatment of Acute Tibial Avulsion Fracture of the Posterior
Cruciate Ligament Using the TightRope Fixation Device.
AB - Avulsion fracture of the posterior cruciate ligament from its tibial insertion is
a rare condition. Early surgical treatment has been regarded as necessary, but
the optimal surgical technique remains unclear. The purpose of this technical
note is to present a novel all-inside arthroscopic reconstruction technique for
bony tibial avulsion fractures of the posterior cruciate ligament using the
TightRope device (Arthrex, Naples, FL).
PMID- 25126508
TI - Endoscopic robotic decompression of the ulnar nerve at the elbow.
AB - Ulnar nerve entrapment can be treated by a number of surgical techniques when
necessary. Endoscopic techniques have recently been developed to access the ulnar
nerve by use of a minimally invasive approach. However, these techniques have
been considered difficult and, many times, dangerous procedures, reserved for
experienced elbow arthroscopic surgeons only. We have developed a new endoscopic
approach using the da Vinci robot (Intuitive Surgical, Sunnyvale, CA) that may be
easier and safer. Standardization of the technique was previously developed in
cadaveric models to achieve the required safety, reliability, and organization
for this procedure, and the technique was then used in a live patient. In this
patient the nerve entrapment symptoms remitted after the surgical procedure. The
robotic surgical procedure presented a cosmetic advantage, as well as possibly
reduced scar formation. This is the first note on this surgical procedure; the
procedure needs to be tested and even evolved until a state-of-the-art standard
is reached.
PMID- 25126509
TI - Arthroscopic Identification of the Anterolateral Ligament of the Knee.
AB - Intense interest has focused on the recent description of the anterolateral
ligament of the knee. Advancing knowledge of its anatomy and function is leading
to a realization of its importance in the rotatory control of the tibia in
anterior cruciate ligament injuries. Reconstruction of this structure will
increasingly become an important goal during anterior cruciate ligament
reconstruction. However, preoperative assessment of this ligament is difficult.
Clinical assessment of rotatory laxity has poor reproducibility, and it is
difficult to define using current imaging techniques. This article is the first
to describe a safe and reproducible arthroscopic technique to allow
identification and examination of the anterolateral ligament of the knee. With
the knee at 90 degrees of flexion, the arthroscope is introduced through the
anterolateral portal to allow clear visualization of the lateral gutter. Under
direct vision, an accessory portal is made over the inferior limit of the lateral
gutter. A shaver is then introduced through this portal and used to debride this
synovial recess and define the anterolateral ligament. This allows the surgeon to
examine the integrity of the anterolateral ligament, in particular its femoral
insertion. If required, this additional information can facilitate the
performance of a more accurate and effective extra-articular reconstruction.
PMID- 25126511
TI - Arthroscopic Treatment of Cartilage Lesions With Microfracture and BST-CarGel.
AB - Bone marrow stimulation techniques for the treatment of articular cartilage
defects such as microfracture so far have solely reproduced mechanically inferior
fibrous cartilage tissue, which might result in unsatisfactory clinical results
at midterm follow-up. A recent study has shown an improvement in repair tissue
quality by enhancing microfracture with a chitosan-based biomaterial (BST-CarGel;
Piramal, Laval, Quebec, Canada). BST-CarGel so far has only been applied by
arthrotomy, which might lead to increased scar tissue formation and thus
compromise recovery time and clinical outcome. We describe a surgical technique
for an arthroscopic treatment of cartilage defects of the knee with microfracture
in combination with BST-CarGel to benefit from improved repair tissue quality and
to reduce arthrotomy-related morbidity.
PMID- 25126510
TI - Reconstruction of the posterolateral corner of the knee with achilles tendon
allograft.
AB - Posterolateral corner injuries of the knee are relatively rare; however, they can
result in significant long-term disability without appropriate treatment. They
often occur in the setting of multiligament knee injuries, and as a result,
diagnosis and management can be challenging. Severe injuries often require
reconstruction, and both anatomic and nonanatomic techniques exist. We describe
our preferred operative technique to reconstruct the fibular collateral ligament
and posterolateral corner using a single Achilles tendon allograft.
PMID- 25126512
TI - Arthroscopic bankart repair: accessory posterior portal with slotted cannula for
lowest capsulolabral access.
AB - We present a novel technique for safe establishment of the accessory posterior
portal using a slotted cannula. Arthroscopic Bankart repair is a common
procedure. A variety of arthroscopic techniques have been described in the
literature, commonly using the posterior portal for visualization and the
anterior portal with a working cannula. The accessory posterior portal enables
elegant access to the lower part of the capsulolabral junction, a firmer grasp
and mobilization of the tissue, quick and easy tool exchange using a slotted
cannula, and clearer suture placement because of the flat, direct working angle.
The skin incision is made small without the need for an arthroscopic cannula, and
the portal location is in a relatively safe zone. The use of the accessory
posterior portal along with a slotted cannula shortens the duration of the
operative procedure and improves safety and performance.
PMID- 25126513
TI - Hybrid Repair of Large Crescent Rotator Cuff Tears Using a Modified SpeedBridge
and Double-Pulley Technique.
AB - An ideal rotator cuff repair maximizes the tendon-bone interface and has adequate
biomechanical strength that can withstand a high level of demand. Arthroscopic
transosseous-equivalent rotator cuff repairs have become popular and have been
shown to be superior to many other methods of fixation. We present an alternative
method of repair for large crescent rotator cuff tears that combines 2 well-known
methods of fixation: modified SpeedBridge (Arthrex, Naples, FL) and double-pulley
techniques. These 2 repair constructs were combined to provide the greatest
amount of compression across the footprint while also providing rigid fixation.
Ultimately, this can provide an optimal environment for healing in otherwise
significant injuries.
PMID- 25126514
TI - Arthroscopic resection of fat pad lesions and infrapatellar contractures.
AB - The infrapatellar fat pad (IFP), also known as Hoffa's fat pad, may be a common
site of pain in the knee because of its susceptibility to injury and its vast
innervation and vascular supply. Patients who have trauma to the IFP may undergo
a process of hemorrhage, inflammation, and fibrosis that may become painful.
Patients with Hoffa's disease in whom conservative treatment with medications,
physical therapy, and injections has failed may receive significant pain relief
and benefit from undergoing arthroscopic subtotal removal of the IFP. We describe
a safe and effective way to perform this procedure allowing excellent
visualization through the use of a superolateral viewing portal.
PMID- 25126515
TI - Avoiding graft-tunnel length mismatch in anterior cruciate ligament
reconstruction: the single-bone plug technique.
AB - Anterior cruciate ligament reconstruction, using autogenous bone-patellar tendon
bone (BTB) as a graft material, is commonly performed in the setting of anterior
cruciate ligament insufficiency. Although bone-patellar tendon-bone autograft has
an extensive track record, showing excellent clinical results, donor-site
morbidity and graft-tunnel mismatch can still be problematic for a subset of
patients. In the setting of a tendon graft that is too long, adequate
interference screw fixation cannot be obtained, typically resulting in a tibial
sided bone plug that achieves less than 15 to 20 mm of bone in the distal tibial
tunnel. We present an easy and effective technique for avoiding the graft-tunnel
mismatch problems that commonly occur in patients who have an excessively long
patellar tendons. This technique involves a simple preoperative planning
algorithm that ultimately results in a single tibial-sided plug harvest. Bony
interference fixation is then obtained on the femoral side and soft-tissue
fixation on the tibial side. This technique allows for satisfactory graft
fixation while avoiding the donor-site morbidity associated with patellar bone
plug harvest.
PMID- 25126517
TI - Chocolate consumption and prevalence of metabolic syndrome in the NHLBI Family
Heart Study.
AB - BACKGROUND & AIMS: Previous studies have suggested that cocoa products, which are
rich sources of flavonoids, may lower blood pressure, serum cholesterol, fasting
blood glucose and improve endothelial function. However, it is unclear whether
consumption of cocoa products including chocolate influences the risk of
metabolic syndrome (MetS). In a cross-sectional design, we sought to examine the
association between chocolate consumption and the prevalence of MetS. METHODS: We
studied 4098 participants from the National Heart, Lung, and Blood Institute
(NHLBI) Family Heart Study aged 25-93 years. Chocolate consumption was assessed
using a semi-quantitative food-frequency questionnaire. MetS was defined using
the NCEP III criteria. Generalized estimating equations were used to estimate
prevalence odds ratios of MetS according to frequency of chocolate intake.
RESULTS: Of the 4098 participants (mean age 51.7 y) included in the analyses,
2206 (53.8%) were female. The prevalence of metabolic syndrome in our population
was 30.2%. Compared with those who did not consume any chocolate, multivariate
adjusted odds ratios (95% CI) for MetS were 1.26 (0.94, 1.69), 1.15 (0.85, 1.55),
and 0.99 (0.66, 1.51) among women who reported chocolate consumption of 1-3
times/ month, 1-4 times/week, and 5+ times/week, respectively. Corresponding
values for men were: 1.13 (0.82, 1.57), 1.02 (0.74, 1.39), and 1.21 (0.79, 1.85).
CONCLUSION: These data do not support an association between chocolate intake and
the prevalence of MetS in US adult men and women.
PMID- 25126519
TI - Genome-wide DNA binding pattern of the homeodomain transcription factor Sine
oculis (So) in the developing eye of Drosophila melanogaster.
AB - The eye of the fruit fly Drosophila melanogaster provides a highly tractable
genetic model system for the study of animal development, and many genes that
regulate Drosophila eye formation have homologs implicated in human development
and disease. Among these is the homeobox gene sine oculis (so), which encodes a
homeodomain transcription factor (TF) that is both necessary for eye development
and sufficient to reprogram a subset of cells outside the normal eye field toward
an eye fate. We have performed a genome-wide analysis of So binding to DNA
prepared from developing Drosophila eye tissue in order to identify candidate
direct targets of So-mediated transcriptional regulation, as described in our
recent article [1]. The data are available from NCBI Gene Expression Omnibus
(GEO) with the accession number GSE52943. Here we describe the methods, data
analysis, and quality control of our So ChIP-seq dataset.
PMID- 25126520
TI - Gene expression signatures affected by ethanol and/or nicotine in normal human
normal oral keratinocytes (NHOKs).
AB - It has been reported that nicotine/alcohol alter epigenetic control and lead to
abrogated DNA methylation and histone modifications, which could subsequently
perturb transcriptional regulation critically important in cellular
transformation. The aim of this study is to determine the molecular mechanisms of
nicotine/alcohol-induced epigenetic alterations and their mechanistic roles in
transcriptional regulation in human adult stem cells. We hypothesized that
nicotine/alcohol induces deregulation of epigenetic machinery and leads to
epigenetic alterations, which subsequently affect transcriptional regulation in
oral epithelial stem cells. As an initiating step we have profiled transcriptomic
alterations induced by combinatory administration of EtOH and nicotine in primary
normal human oral keratinocytes. Here we provide detailed experimental methods,
analysis and information associated with our data deposited into Gene Expression
Omnibus (GEO) under GSE57634. Our data provide comprehensive transcriptomic map
describing molecular changes induced by EtOH and nicotine on normal human oral
keratinocytes.
PMID- 25126522
TI - Lipid nanoceuticals: Current status and future perspective.
PMID- 25126518
TI - Aging-dependent changes in rat heart mitochondrial glutaredoxins--Implications
for redox regulation.
AB - Clinical and animal studies have documented that hearts of the elderly are more
susceptible to ischemia/reperfusion damage compared to young adults. Recently we
found that aging-dependent increase in susceptibility of cardiomyocytes to
apoptosis was attributable to decrease in cytosolic glutaredoxin 1 (Grx1) and
concomitant decrease in NF-kappaB-mediated expression of anti-apoptotic proteins.
Besides primary localization in the cytosol, Grx1 also exists in the
mitochondrial intermembrane space (IMS). In contrast, Grx2 is confined to the
mitochondrial matrix. Here we report that Grx1 is decreased by 50-60% in the IMS,
but Grx2 is increased by 1.4-2.6 fold in the matrix of heart mitochondria from
elderly rats. Determination of in situ activities of the Grx isozymes from both
subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria revealed that Grx1 was
fully active in the IMS. However, Grx2 was mostly in an inactive form in the
matrix, consistent with reversible sequestration of the active-site cysteines of
two Grx2 molecules in complex with an iron-sulfur cluster. Our quantitative
evaluations of the active/inactive ratio for Grx2 suggest that levels of dimeric
Grx2 complex with iron-sulfur clusters are increased in SSM and IFM in the hearts
of elderly rats. We found that the inactive Grx2 can be fully reactivated by
sodium dithionite or exogenous superoxide production mediated by xanthine
oxidase. However, treatment with rotenone, which generates intramitochondrial
superoxide through inhibition of mitochondrial respiratory chain Complex I, did
not lead to Grx2 activation. These findings suggest that insufficient ROS
accumulates in the vicinity of dimeric Grx2 to activate it in situ.
PMID- 25126521
TI - The RPTEC/TERT1 cell line models key renal cell responses to the environmental
toxicants, benzo[a]pyrene and cadmium.
AB - We have characterized initial canonical responses to two environmental toxicants,
cadmium (Cd) and benzo[a]pyrene (B[a]P), in a novel in vitro model derived from
renal proximal tubule epithelial cells (RPTEC) of a healthy human donor. The
RPTEC/TERT1 cell line has been immortalized using the human telomerase reverse
transcriptase (hTERT) subunit only and does not exhibit chromosomal
abnormalities. RPTEC/TERT1 cells were exposed to single-compound and binary
mixtures of Cd and B[a]P, known or suspected renal toxicants respectively. Cells
exhibited cytotoxicity to concentrations of B[a]P and Cd as low as 1 nm and 3
MUM, respectively. RPTEC/TERT1 cells exhibited compound-specific gene expression
responses when exposed to 0.01-1 MUM B[a]P and 0.1-10 MUM Cd. A significant
increase in the expression of genes coding for B[a]P metabolizing enzymes
(CYP1A1, CYP1B1) occurred in a dose and time dependent manner at 3, 6, and 24 h
post exposure. Likewise, a significant increase in the heavy metal responsive
gene MT2A was observed following exposure to Cd. The EROD activity assay
confirmed significant increases in CYP1(A/B) activity after 24 h of exposure to
B[a]P which was not affected by the presence of Cd. Co-exposure to low
concentrations of Cd and B[a]P were consistent with changes in gene expression as
seen with single-compound exposures. These experiments are the first to provide
information regarding toxicological responses in the RPTEC/TERT1 cell line that
model those of the target tissue. We conclude that these cells can provide a
useful tool for future toxicological studies.
PMID- 25126523
TI - Pharmacoeconomics guidelines: The need of hour for India.
AB - Although the government pays for approximately 20% of drugs used in India,
private out-of-pocket expenditure in India on health-care is one of the highest
in the world. Preparing pharmacoeconomics guidelines will be an important step in
order to establish Health Technology Assessment (HTA) in India. Areas in which
HTA could be applied in the Indian context include, drug pricing, development of
clinical practice guidelines and prioritizing interventions that represent the
greatest value within a limited budget. All this calls for action, both by
government and civil-society organizations, to make access to essential medicines
a priority.
PMID- 25126524
TI - Formulation and evaluation of stimuli-sensitive hydrogels of timolol maleate and
brimonidine tartrate for the treatment of glaucoma.
AB - BACKGROUND: Stimuli-sensitive hydrogels are hydrophilic, three-dimensional,
polymeric network structure capable of imbibing large amounts of water or
biological fluids on stimulation, such as pH, temperature, and ionic change.
Owing to the drawback of conventional therapy for ocular delivery, and to provide
additive effect on intraocular pressure (IOP) reduction, stimuli sensitive
hydrogel membranes containing a combination of timolol maleate and brimonidine
tartrate were formulated for the treatment of glaucoma. MATERIALS AND METHODS:
Stimuli-sensitive hydrogel were formulated by timolol maleate and brimonidine
tartrate. Poly acrylic acid (carbopol C 934p) is used as a gelling agent,
hydroxylpropyl methylcellulose as viscolizer, sodium chloride as tonicity agent.
Bezalkonium chloride as preservative. White rabbits of both sexes, weighing
between 2 and 3 kg were used for the study. Stirring of ingredients in pH 4
phosphate buffers at high speed was carried out. RESULT: Viscosity of the
prepared hydrogels lies in the optimum range that is, 25-55 cps. Infrared
spectroscopy studies show that there is no interaction between the drug and
polymer. Drug released up to 90% at the end of 8 h. The hydrogel membranes were
found to be sterile, nonirritant to the eye. Marketed formulation showed a
decrease in IOP up to 14 mmHg at the end of 5 h and then elimination of drug, F2
and F6 maintain the sustained effect up to 12 h. CONCLUSION: Stimuli-sensitive
hydrogels was successfully formulated and evaluated for rheological studies, drug
release studies, drug interaction studies, sterility studies, ocular irritation
studies, and in vivo studies. IOP lowering activity of the combination of timolol
maleate and brimonidine tartrate in stimuli-sensitive hydrogel was better when
compared with alone medication, which shows the additive effect of combination
medication.
PMID- 25126525
TI - Nanovesicles for transdermal delivery of felodipine: Development,
characterization, and pharmacokinetics.
AB - AIM: The research traces development of nanovesicles to attain enhanced
transdermal delivery of felodipine and also investigates parameters for
optimization of variable membrane compositions containing soya- and egg lecithin
and edge activator. MATERIALS AND METHODS: Rotary evaporation sonication method
was employed to obtain tranfersomal formulation that was characterized for
vesicle shape and size, polydispersity index (PDI), zeta potential, entrapment
and loading efficiency, deformability index and in vitro skin permeation.
RESULTS: Spherical nanovesicles of 75.71 +/- 5.4 nm with PDI 0.228 and zeta
potential of -49.8 were adjudged as the best formulation (MF8). MF8 displayed
maximum entrapment and loading efficiency with a high deformability index of
119.68. In vitro permeation across rat skin by MF8 reported 256% enhancement in
permeation (flux = 23.72 +/- 0.64) when compared with transdermal control
formulation and followed zero order kinetics (Case-II). Pharmacokinetic studies
revealed that transdermal administration, in contrast to oral delivery provided
relatively constant, sustained blood concentration with minimal plasma
fluctuation, rapid and prolonged peak time. The relative bioavailability of
felodipine was found 358.42% versus oral administration that was well supported
by the outcomes of confocal laser scanning microscopic studies that suggested
rapid permeation of drugs to across dermal layers. CONCLUSION: The results
conclude that composition variation and method of preparation elicited
significant effect on the vesicle characteristic and proved the transcendency of
felodipine loaded transfersomes.
PMID- 25126526
TI - Preparation and characterization of amorphous ezetimibe nanosuspensions intended
for enhancement of oral bioavailability.
AB - OBJECTIVE: The objective of this study was to prepare and investigate better and
stable amorphous ezetimibe nanosuspensions for oral bioavailability enhancement.
MATERIALS AND METHODS: Nanosuspensions of ezetimibe were prepared by solvent
antisolvent precipitation technique using the surfactant, Tween 80 as stabilizer.
The nanosuspension preparation was optimized for particle size by investigating
two factors that is, solvent:antisolvent ratio and surfactant concentration, at
three levels. The formulations were characterized for particle size, surface
morphology, crystallinity, zeta potential, saturation solubility, in vitro drug
release and in vivo drug absorption. RESULTS: The nanosuspensions of ezetimibe
were successfully prepared using solvent-antisolvent precipitation. The two
factors solvent:antisolvent ratio and surfactant concentration influenced the
particle size of the nanosuspensions prepared. Nanosuspensions were smooth and
spherical. The X-ray powdered diffraction and differential scanning calorimetry
results indicated that the antisolvent-solvent method led to the amorphization of
ezetimibe. Under storage, the amorphous ezetimibe nanosuspensions demonstrated
significant physical stability. Ezetimibe nanosuspensions increased the
saturation solubility to an extent of 4-times. Ezetimibe nanosuspensions
completely dissolved in the dissolution medium within 1 h, while pure drug was
dissolved up to 42% during same time. The Cmax with ezetimibe nanosuspension was
approximately 3-fold higher when compared with that of ezetimibe conventional
suspensions administered orally. CONCLUSIONS: Stable amorphous ezetimibe
nanosuspensions were successfully prepared and these nanosuspensions demonstrated
dramatic improvement in oral bioavailability of the active.
PMID- 25126527
TI - Comparison of effectiveness of curcumin with triamcinolone acetonide in the gel
form in treatment of minor recurrent aphthous stomatitis: A randomized clinical
trial.
AB - INTRODUCTION: Recurrent aphthous stomatitis (RAS) is an unfortunately most common
disease occurring in oral cavity. Although the lesion is usually self-limited,
its painful presentation, high frequency of occurrence, and multifactorial
etiology leads to significant morbidity. So, an efficient therapeutic strategy is
needed to provide relief to the patients. AIM: To assess and compare the efficacy
of Curcumin with Triamcinolone acetonide in the gel form in treatment of minor
RAS. MATERIALS AND METHODS: As a randomized clinical trial, 60 patients of either
sex with clinically diagnosed RAS were randomly divided into 2 groups-Curcumin
gel group (Group I) and Triamcinolone Acetonide gel group (Group II). Patients in
either group were asked to apply the gel three times a day on each ulcer.
Assessment of efficacy of gel was done on the basis of time required for
regression in pain, size, and number of the ulcers. RESULTS: The results showed
significant difference in size, pain, number, and duration of ulcers in Group I
and Group II within a period of 7 days. However, no significant difference was
noted in both the groups in the treatment of RAS. To evaluate the efficacy, Mann
Whitney U test was used and statistical analysis was done using Statistical
Package for the Social Sciences (SPSS) 19 software. CONCLUSION: Curcumin has
strong antioxidant, with anti-inflammatory, immunomodulatory and analgesic
properties, which according to the results obtained from the present study, can
be used as an effective alternative to steroids in treatment of RAS.
PMID- 25126529
TI - Nanotechnology: The vision of 2025.
PMID- 25126528
TI - Albumin nanoparticles coated with polysorbate 80 as a novel drug carrier for the
delivery of antiretroviral drug-Efavirenz.
AB - PURPOSE OF THE STUDY: The antiretroviral therapy (ART) has dramatically improved
human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)
treatment, prevention and also has been found to increase the lifespan of
HIV/AIDS patients by providing durable control of the HIV replication in
patients. Efavirenz is a non-nucleoside reverse transcriptase inhibitor of HIV-1.
The purpose of this study is to formulate efavirenz-loaded bovine serum albumin
nanoparticles to improve efavirenz delivery into various organs. MATERIALS AND
METHODS: Nanoparticles were prepared by desolvation technique and coated with
polysorbate 80. Ethanol, glutaraldehyde, and mannitol were used as desolvating,
cross linking agent, and cryoprotectant, respectively. Drug to polymer ratio was
chosen at five levels from 1:2, 1:3, 1:4, 1:5, and 1:6 (by weight). The
formulated nanoparticles were characterized for Fourier Transform Infrared (FT
IR) spectroscopy, differential scanning calorimetry (DSC) studies, entrapment
efficiency, particle size, surface charge, surface morphology, in vitro drug
release, release kinetics, stability studies, and biodistribution studies.
RESULTS AND MAJOR CONCLUSION: The particle size of the prepared formulations was
found below 250nm with narrow size distribution, spherical in shape and showed
good entrapment efficiency (45.62-72.49%). The in vitro drug release indicated
biphasic release and its data were fitted to release kinetics models and release
pattern was Fickian diffusion controlled release profile. The prepared
nanoparticles increased efavirenz delivery into various organs by several fold in
comparison with the free drug.
PMID- 25126530
TI - Role of pharmacists in retailing of drugs.
PMID- 25126531
TI - Method development and validation of liquid chromatography-tandem/mass
spectrometry for aldosterone in human plasma: Application to drug interaction
study of atorvastatin and olmesartan combination.
AB - In the present investigation, a simple and sensitive liquid chromatography-tandem
mass spectrometry (LC/MS/MS) method was developed for the quantification of
aldosterone (ALD) a hormone responsible for blood pressure in human plasma. The
developed method was validated and extended for application on human subjects to
study drug interaction of atorvastatin (ATSV) and olmesartan (OLM) on levels of
ALD. The ALD in plasma was extracted by liquid-liquid extraction with 5 mL
dichloromethane/ethyl ether (60/40% v/v). The chromatographic separation of ALD
was carried on Xterra, RP-Column C18 (150 mm* 4.6 mm * 3.5 MUm) at 30 degrees C
followed by four-step gradient program composed of methanol and water. Step 1
started with 35% methanol for first 1 min and changed linearly to 90% in next 1.5
min in Step 2. Step 3 lasted for next 2 min with 90% methanol. The method finally
concluded with Step 4 to achieve initial concentration of methanol that is, 35%
thus contributing the total method run time of 17.5 min. The flow rate was 0.25
mL/min throughout the process. The developed method was validated for
specificity, accuracy, precision, stability, linearity, sensitivity, and
recovery. The method was linear and found to be acceptable over the range of 50
800 ng/mL. The method was successfully applied for the drug interaction study of
ATSV + OLM in combination against OLM treatment on blood pressure by quantifying
changes in levels of ALD in hypertensive patients. The study revealed levels of
ALD were significantly higher in ATSV + OLM treatment condition when compared to
OLM as single treated condition. This reflects the reason of low effectiveness of
ATSV + OLM in combination instead of synergistic activity.
PMID- 25126532
TI - Multi criteria decision making to select the best method for the preparation of
solid lipid nanoparticles of rasagiline mesylate using analytic hierarchy
process.
AB - The objective of this study was to select best method for the development of
rasagiline mesylate (RM) loaded nanoscale solid lipid particles using analytic
hierarchy process (AHP). Improper method selection may lead to waste of time,
loss of material and financial resources. One of the possibilities to overcome
these difficulties, AHP was employed to find the suitable method. In the AHP, a
decision of hierarchy was constructed with a goal, criteria, sub-criteria, and
alternatives. After constructing the AHP, the expert choice software was used to
compute the overall priority of criteria, sub-criteria and alternatives. The best
alternative selected was based on the highest priority. Nanoscale solid lipid
particles of RM was formulated by the selected microemulsion method (M4) and it
shows the particle size, polydispersity index and zeta potential were within
acceptable limits. Drug content and entrapment efficiency of the RM-solid lipid
nanoparticles were 97.26% and 86.57%, respectively. This study concludes that the
AHP was viable and effective tool for selecting a most suitable method for the
fabrication of RM loaded nanoscale solid lipid particles.
PMID- 25126533
TI - Comparative antidiarrheal and antiulcer effect of the aqueous and ethanolic stem
bark extracts of Tinospora cordifolia in rats.
AB - Tinospora cordifolia is indigenous to the tropical areas of India, Myanmar and
Sri Lanka. The use of plant as remedy for diarrhea and ulcer is well-documented
in Ayurvedic system of medicine. However, pharmacological evidence does not exist
to substantiate its therapeutic efficacy for the same. The aim was to investigate
the antidiarrheal and antiulcer activity of ethanolic and aqueous extracts of T.
cordifolia in rats. The antidiarrheal activity of T. cordifolia extracts was
evaluated by castor oil and magnesium sulfate-induced diarrhea using parameters
such as onset of diarrhea, number of wet stools, total number of stool and weight
of total number of stools. The antiulcer activity of extracts was investigated
using ethanol and pylorus ligation-induced ulcer. Furthermore, tissue antioxidant
parameters such as reduced glutathione, catalase activity and lipid peroxidation
level were also investigated. Tinospora cordifolia extracts were more efficacious
in reducing number of total stools in both the models of diarrhea and showed a
dose-dependent antidiarrheal effect. The antiulcer activity of the extracts was
confirmed by a reduction in ulcer index along with the decrease in gastric
volume, total acidity, and an increase in pH of gastric content in both the
models. The obtained results have established a pharmacological evidence for the
folkloric use of the T. cordifolia as antidiarrhoeal and antiulcer agent.
PMID- 25126534
TI - Evaluation of analgesic activity of perindopril in albino mice.
AB - The aim was to evaluate the analgesic activity of perindopril in chemical,
thermal and mechanical pain on Swiss albino mice. A total of 54 albino mice
(Swiss strain) weighing 25-30 g were allocated to each experimental model and in
each model there were three groups. The control group received normal saline (25
ml/kg) per orally, standard group received pentazocine (10 mg/kg) intra
peritoneal and test groups received perindopril (1 mg/kg) per orally. Perindopril
and normal saline was administered 2 h before, whereas the pentazocine was
administered 15 min prior to Eddy's hot plate, writhing and tail clip methods.
The decrease in number of writhes, the delay in reaction time in tail clip and
Eddy's hot plate method denoted the analgesic activity. Perindopril decreased the
number of writhes, delayed the reaction time in tail clip and Eddy's hot plate
method considerably when compared with control (normal saline), but less when
compared with standard (pentazocine). Perindopril exhibits analgesic activity in
thermal, chemical, and mechanical pain models in albino mice.
PMID- 25126535
TI - Pharmacodynamic interaction of green tea extract with hydrochlorothiazide against
ischemia-reperfusion injury-induced myocardial infarction.
AB - Globally, the rate of development of myocardial diseases and hypertension is very
common, which is responsible for incremental morbidity and mortality statistics.
Treatment of ischemic hypertensive patients with diuretics such as
hydrochlorothiazide (HCTZ) can precipitate myocardial infarction due to
hypokalemia. This study was undertaken to evaluate the pharmacodynamic
interaction of green tea extract (GTE) with HCTZ against ischemia-reperfusion
induced myocardial toxicity. Wistar albino rats of either sex were taken and
pretreated with high (500 mg/kg, p.o.) and low (100 mg/kg, p.o.) dose of GTE for
30 days. Standard, high and low dose of interactive groups received HCTZ (10
mg/kg, p.o.) for last 7 days. Ischemia-reperfusion injury was induced by modified
Lagendorff apparatus, and the effect of different treatments was evaluated by
percentage recovery in terms of heart rate and developed tension, serum
biomarkers, and heart tissue antioxidant levels. Prophylactic treatment groups,
such as high and low dose of GTE and their interactive groups with HCTZ,
exhibited significant percentage recovery in terms of heart rate and developed
tension. Apart from that, significant increase in superoxide dismutase and
catalase, decrease in thiobarbituric acid reactive species in heart tissue, as
well as significant decrease in serum lactate dehydrogenase, creatinine
phosphokinase-MB and N-acetylcysteine levels have also been documented. The
present findings clearly suggest that GTE dose-dependently reduces myocardial
toxicity due to ischemia, and combination with HCTZ can reduce the associated
side-effects and exhibits myocardial protection.
PMID- 25126536
TI - Role of different biodegradable polymers on the permeability of ciprofloxacin.
AB - Since permeability across biological membranes is a key factor in the absorption
and distribution of drugs, drug permeation characteristics of three oral
suspensions of ciprofloxacin were designed and compared. The three suspensions of
ciprofloxacin were prepared by taking biodegradable polymers such as carbopol
934, carbopol 940, and hydroxypropyl methylcellulose (HPMC). The permeability
study was performed by using a Franz diffusion cell through both synthetic
cellulose acetate membrane and excised goat gastrointestinal membranes in acidic
as well as alkaline pH. To know the permeability of drug from
control/formulations through different membranes in acidic/alkaline pH,
cumulative percentage drug permeation, apparent permeability (Papp), flux, and
enhancement ratio (ER) were calculated. Considering Papp and flux values of all
formulations, it is evident that formulation containing HPMC was the most
beneficial for improving permeation and diffusivity of ciprofloxacin even after
16 h. Hence, this preparation may be considered as the most suitable formulation
to obtain prolonged release action of the drug. The ER values of all
formulations, through excised goat intestinal mucosal membrane in alkaline pH,
were higher than those formulations through goat stomach mucosal membrane in
acidic pH. Enhancement ratio values of those formulations indicate that the
permeability of the drug was more enhanced by the polymers in the intestinal
part, leading to more bioavailability and prolonged action in that portion of the
gastrointestinal tract. It may also be concluded from our results that HPMC
containing formulation was the best suspension, which may show effective
controlled release action. Even carbopol containing formulations might also
produce controlled release action.
PMID- 25126537
TI - A simple reversed phase high-performance liquid chromatography (RP-HPLC) method
for determination of curcumin in aqueous humor of rabbit.
AB - This article describes a simple and rapid method for determination of curcumin
(diferuloylmethane) in aqueous humor of rabbit using high-performance liquid
chromatography (HPLC). Analysis was performed using a C-18 column (250 * 4.6 mm,
5 MU luna) by isocratic elution with a mobile phase containing 25 mM potassium
dihydrogen orthophosphate (pH 3.5): Acetonitrile (40:60) and detection at 424 nm
using a photodiode array (PDA) detector for curcumin. The regression data for
curcumin showed a good linear relationship with r(2)> 0.998 over the
concentration range of 0.1-10 MUg ml(-1). Relative standard deviations (RSD) for
the intraday and interday coefficient of variations for the assay were less than
5.0 and 8.5, respectively. The recovery of the method was between 79.8-83.6%. The
quantification limit of the method for curcumin was 0.01 MUg ml(-1). This method
has good accuracy, precision, and quantitation limit. It is also concluded that
the method is useful for measuring very low curcumin concentrations in aqueous
humor.
PMID- 25126538
TI - Collaborative Care in NSCLC; the Role of Early Palliative Care.
AB - The management of non-small cell lung cancer (NSCLC) has evolved into a
multidisciplinary team approach that traditionally has involved medical oncology,
radiation oncology, and thoracic surgery. However, in the era of personalized
medicine the importance of molecular diagnostics requires adequate tissue for
histologic subtyping and molecular testing and thus requires the engagement of
other subspecialties such as pathology, respirology, and interventional
radiology. Unfortunately in 2014, the majority of patients presenting with NSCLC
will succumb to their disease and the early integration of palliative care into
the treatment strategy will improve the quality of life and end-of-life care of
our patients and may in fact improve their overall survival.
PMID- 25126541
TI - Anima: modular workflow system for comprehensive image data analysis.
AB - Modern microscopes produce vast amounts of image data, and computational methods
are needed to analyze and interpret these data. Furthermore, a single image
analysis project may require tens or hundreds of analysis steps starting from
data import and pre-processing to segmentation and statistical analysis; and
ending with visualization and reporting. To manage such large-scale image data
analysis projects, we present here a modular workflow system called Anima. Anima
is designed for comprehensive and efficient image data analysis development, and
it contains several features that are crucial in high-throughput image data
analysis: programing language independence, batch processing, easily customized
data processing, interoperability with other software via application programing
interfaces, and advanced multivariate statistical analysis. The utility of Anima
is shown with two case studies focusing on testing different algorithms developed
in different imaging platforms and an automated prediction of alive/dead C.
elegans worms by integrating several analysis environments. Anima is a fully open
source and available with documentation at www.anduril.org/anima.
PMID- 25126539
TI - Hepatic radioembolization as a bridge to liver surgery.
AB - Treatment of oncologic disease has improved significantly in the last decades and
in the future a vast majority of cancer types will continue to increase
worldwide. As a result, many patients are confronted with primary liver cancers
or metastatic liver disease. Surgery in liver malignancies has steeply improved
and curative resections are applicable in wider settings, leading to a prolonged
survival. Simultaneously, radiofrequency ablation (RFA) and liver transplantation
(LTx) have been applied more commonly in oncologic settings with improving
results. To minimize adverse events in treatments of liver malignancies,
locoregional minimal invasive treatments have made their appearance in this
field, in which radioembolization (RE) has shown promising results in recent
years with few adverse events and high response rates. We discuss several other
applications of RE for oncologic patients, other than its use in the palliative
setting, whether or not combined with other treatments. This review is focused on
the role of RE in acquiring patient eligibility for radical treatments, like
surgery, RFA, and LTx. Inducing significant tumor reduction can downstage
patients for resection or, through attaining stable disease, patients can stay on
the LTx waiting list. Hereby, RE could make a difference between curative of
palliative intent in oncologic patient management. Prior to surgery, the future
remnant liver volume might be inadequate in some patients. In these patients,
forming an adequate liver reserve through RE leads to prolonged survival without
risking post-operative liver failure and minimizing tumor progression while
inducing hypertrophy. In order to optimize results, developments in procedures
surrounding RE are equally important. Predicting the remaining liver function
after radical treatment and finding the right balance between maximum tumor
irradiation and minimizing the chance of inducing radiation-related complications
are still challenges.
PMID- 25126540
TI - Genetically modeled mice with mutations in mitochondrial metabolic enzymes for
the study of cancer.
AB - Mitochondrial dysfunction has long been implicated in progression of cancer. As a
paradigm, the "Warburg effect," which by means of a switch toward anaerobic
metabolism enables cancer cells to proliferate in oxygen limiting conditions, is
well established. Besides this metabolic transformation of tumors, it has been
discovered that mutations in genes encoding mitochondrial proteins are the
etiological factors in different types of cancer. This confers to mitochondrial
dysfunction a causative role, rather than resultant, in tumor genesis beyond its
role in tumor progression and development. Mitochondrial proteins encoded by
tumor-suppressor genes are part of the succinate-dehydrogenase, the fumarate
hydratase, and the mitochondrial isocitrate-dehydrogenase enzymes, all of them
participating in the Krebs cycle. The spectrum of tumors associated with
mutations in these genes is becoming larger and varies between each enzyme.
Several mechanisms of tumorigenesis have been proposed for the different
enzymatic defects, most of them based on studies using cellular and animal
models. Regarding the molecular pathways implicated in the oncogenic
transformation, one of the first accepted theories was based on the constitutive
expression of the hypoxia-inducible factor 1alpha (Hif1alpha) at normal oxygen
tension, a theory referred to as "pseudo-hypoxic drive." This mechanism has been
linked to the three types of mutations, thus suggesting a central role in cancer.
However, other alternative molecular processes, such as oxidative stress or
altered chromatin remodeling, have been also proposed to play an onco-pathogenic
role. In the recent years, the role of oncometabolites, a new concept emerged
from biochemical studies upon these tumors, has acquired relevance as responsible
for tumor formation. Nevertheless, the actual contribution of each of these
mechanisms has not been definitively established. In this review, we summarize
the results obtained from mouse strains genetically modified in the three
different enzymes.
PMID- 25126542
TI - The effect of citrus peel extracts on cytokines levels and T regulatory cells in
acute liver injury.
AB - BACKGROUND: T cell-mediated immune responses contribute to the hepatocellular
injury during autoimmune hepatitis, viral infection, and hepatotoxins.
Pharmacological compounds regulating immune responses are suitable candidates for
prevention/treatment of this pathology. Therefore, the main aim of this study was
to define the effects of antioxidant, anti-inflammatory mixture of citrus peel
extract (CPE) on the immune-mediated liver injury. METHODS: The influence of CPE
on liver injury was determined by the activity of transaminases in plasma and the
histological changes. Anti-inflammatory and antioxidant effects were studied by
measuring frequency of T regulatory cells (Tregs), cytokines (TNF-alpha, IL-10,
and IFN-gamma), and nitric oxide levels. RESULTS: The CPE application notably
prevents development of liver injury through decreasing levels of both cytokines
(TNF-alpha, INF) and regulatory T cells and increasing levels of IL-10. CPE
injection also diminished the serum NO, which in turn resulted in evident
reduction of the liver damage. CONCLUSION: Our findings represent the primary
preclinical data indicating that the CPE in vivo could ameliorate Con A induced
hepatitis. The low dose of CPE most likely can be used for the treatment of the T
cell-mediated liver injury as in autoimmune hepatitis, alcoholic hepatitis, and
chronic viral hepatitis.
PMID- 25126545
TI - Visualization of polypropylene and polyvinylidene fluoride slings in perineal
ultrasound and correlation with clinical outcome.
AB - INTRODUCTION AND HYPOTHESIS: Complications and malfunctioning after TOT can occur
due to several factors, such as the material of the sling. The aim of the present
study is to evaluate morphology and functionality of two types of slings (PVDF;
polypropylene) in vivo using perineal ultrasound (PUS). MATERIALS: In n = 47
women with TOT four criteria for PUS were taken and checked for possible
differences: vertical stability of the sling position during Valsalva manoeuvre
and contraction; distance "sling to urethra"; width of the sling and condition of
the selvedges. RESULTS: We observed an increased vertical displacement of the PP
slings, a significantly smaller variance to the extent of the displacement in
PVDF-slings (P < 0.01), a significantly larger distance between sling and urethra
(P < 0.001) in PVDF-slings, and a significantly smaller width of the PP-slings (P
< 0.0001). CONCLUSION: Significant differences were found between the slings
according to the four criteria. There was no difference established between the
slings in the improvement of continence and no significant influence of the
parameters was found for the resulting state of continence. In future studies,
PUS may help to link differences in the morphology and functionality of in vivo
slings to their material properties.
PMID- 25126544
TI - Formulation and optimization of polymeric nanoparticles for intranasal delivery
of lorazepam using Box-Behnken design: in vitro and in vivo evaluation.
AB - The aim of the present study was to optimize lorazepam loaded PLGA nanoparticles
(Lzp-PLGA-NPs) by investigating the effect of process variables on the response
using Box-Behnken design. Effect of four independent factors, that is, polymer,
surfactant, drug, and aqueous/organic ratio, was studied on two dependent
responses, that is, z-average and % drug entrapment. Lzp-PLGA-NPs were
successfully developed by nanoprecipitation method using PLGA as polymer,
poloxamer as surfactant and acetone as organic phase. NPs were characterized for
particle size, zeta potential, % drug entrapment, drug release behavior, TEM, and
cell viability. Lzp-PLGA-NPs were characterized for drug polymer interaction
using FTIR. The developed NPs showed nearly spherical shape with z-average 167
318 d.nm, PDI below 0.441, and -18.4 mV zeta potential with maximum % drug
entrapment of 90.1%. In vitro drug release behavior followed Korsmeyer-Peppas
model and showed initial burst release of 21.7 +/- 1.3% with prolonged drug
release of 69.5 +/- 0.8% from optimized NPs up to 24 h. In vitro drug release
data was found in agreement with ex vivo permeation data through sheep nasal
mucosa. In vitro cell viability study on Vero cell line confirmed the safety of
optimized NPs. Optimized Lzp-PLGA-NPs were radiolabelled with Technitium-99m for
scintigraphy imaging and biodistribution studies in Sprague-Dawley rats to
establish nose-to-brain pathway.
PMID- 25126543
TI - Ligation strategies for targeting liposomal nanocarriers.
AB - Liposomes have been exploited for pharmaceutical purposes, including diagnostic
imaging and drug and gene delivery. The versatility of liposomes as drug carriers
has been demonstrated by a variety of clinically approved formulations. Since
liposomes were first reported, research of liposomal formulations has progressed
to produce improved delivery systems. One example of this progress is stealth
liposomes, so called because they are equipped with a PEGylated coating of the
liposome bilayer, leading to prolonged blood circulation and improved
biodistribution of the liposomal carrier. A growing research area focuses on the
preparation of liposomes with the ability of targeting specific tissues. Several
strategies to prepare liposomes with active targeting ligands have been developed
over the last decades. Herein, several strategies for the functionalization of
liposomes are concisely summarized, with emphasis on recently developed
technologies for the covalent conjugation of targeting ligands to liposomes.
PMID- 25126547
TI - Biotemplated synthesis of anatase titanium dioxide nanoparticles via
lignocellulosic waste material.
AB - Anatase titanium dioxide nanoparticles (TiO2-NPs) were synthesized by sol-gel
method using rice straw as a soft biotemplate. Rice straw, as a lignocellulosic
waste material, is a biomass feedstock which is globally produced in high rate
and could be utilized in an innovative approach to manufacture a value-added
product. Rice straw as a reliable biotemplate has been used in the sol-gel method
to synthesize ultrasmall sizes of TiO2-NPs with high potential application in
photocatalysis. The physicochemical properties of titanium dioxide nanoparticles
were investigated by a number of techniques such as X-ray diffraction analysis
(XRD), transmission electron microscopy (TEM), Fourier transform infrared
spectroscopy (FTIR), Raman spectroscopy, thermogravimetric analysis (TGA),
ultraviolet visible spectra (UV-Vis), and surface area and pore size analysis.
All results consensually confirmed that particle sizes of synthesized titanium
dioxide were template-dependent, representing decrease in the nanoparticles sizes
with increase of biotemplate concentration. Titanium dioxide nanoparticles as
small as 13.0 +/- 3.3 nm were obtained under our experimental conditions.
Additionally, surface area and porosity of synthesized TiO2-NPs have been
enhanced by increasing rice straw amount which results in surface modification of
nanoparticles and potential application in photocatalysis.
PMID- 25126546
TI - Genome-wide uncovering of STAT3-mediated miRNA expression profiles in colorectal
cancer cell lines.
AB - Colorectal cancer (CRC) is one of the most common malignancies resulting in high
mortality worldwide. Signal transducer and activator of transcription 3 (STAT3)
is an oncogenic transcription factor which is frequently activated and aberrantly
expressed in CRC. MicroRNAs (miRNAs) are a class of small noncoding RNAs which
play important roles in many cancers. However, little is known about the global
miRNA profiles mediated by STAT3 in CRC cells. In the present study, we applied
RNA interference to inhibit STAT3 expression and profiled the miRNA expression
levels regulated by STAT3 in CRC cell lines with deep sequencing. We found that
26 and 21 known miRNAs were significantly overexpressed and downexpressed,
respectively, in the STAT3-knockdown CRC cell line SW480 (SW480/STAT3-siRNA)
compared to SW480 transfected with scrambled siRNAs (SW480/siRNA-control). The
miRNA expression profiling was then validated by quantitative real-time PCR for
selected known miRNAs. We further predicted the putative target genes for the
dysregulated miRNAs and carried out functional annotation including GO enrichment
and KEGG pathway analysis for selected miRNA targets. This study directly depicts
STAT3-mediated miRNA profiles in CRC cells, which provides a possible way to
discover biomarkers for CRC therapy.
PMID- 25126548
TI - Assessment of waveform similarity in clinical gait data: the linear fit method.
AB - The assessment of waveform similarity is a crucial issue in gait analysis for the
comparison of kinematic or kinetic patterns with reference data. A typical
scenario is in fact the comparison of a patient's gait pattern with a relevant
physiological pattern. This study aims to propose and validate a simple method
for the assessment of waveform similarity in terms of shape, amplitude, and
offset. The method relies on the interpretation of these three parameters,
obtained through a linear fit applied to the two data sets under comparison
plotted one against the other after time normalization. The validity of this
linear fit method was tested in terms of appropriateness (comparing real gait
data of 34 patients with cerebrovascular accident with those of 15 healthy
subjects), reliability, sensitivity, and specificity (applying a cluster analysis
on the real data). Results showed for this method good appropriateness, 94.1% of
sensitivity, 93.3% of specificity, and good reliability. The LFM resulted in a
simple method suitable for analysing the waveform similarity in clinical gait
analysis.
PMID- 25126550
TI - Reduction of experimental cerebral malaria and its related proinflammatory
responses by the novel liposome-based beta-methasone nanodrug.
AB - Cerebral malaria (CM) is a severe complication of and a leading cause of death
due to Plasmodium falciparum infection. CM is likely the result of interrelated
events, including mechanical obstruction due to parasite sequestration in the
microvasculature, and upregulation of Th1 immune responses. In parallel, blood
brain-barrier (BBB) breakdown and damage or death of microglia, astrocytes, and
neurons occurs. We found that a novel formulation of a liposome-encapsulated
glucocorticosteroid, beta-methasone hemisuccinate (nSSL-BMS), prevents
experimental cerebral malaria (ECM) in a murine model and creates a survival time
window, enabling administration of an antiplasmodial drug before severe anemia
develops. nSSL-BMS treatment leads to lower levels of cerebral inflammation,
expressed by altered levels of corresponding cytokines and chemokines. The
results indicate the role of integrated immune responses in ECM induction and
show that the new steroidal nanodrug nSSL-BMS reverses the balance between the
Th1 and Th2 responses in malaria-infected mice so that the proinflammatory
processes leading to ECM are prevented. Overall, because of the
immunopathological nature of CM, combined immunomodulator/antiplasmodial
treatment should be considered for prevention/treatment of human CM and long-term
cognitive damage.
PMID- 25126549
TI - Cell death and inflammatory bowel diseases: apoptosis, necrosis, and autophagy in
the intestinal epithelium.
AB - Cell death mechanisms have been associated with the development of inflammatory
bowel diseases in humans and mice. Recent studies suggested that a complex
crosstalk between autophagy/apoptosis, microbe sensing, and enhanced endoplasmic
reticulum stress in the epithelium could play a critical role in these diseases.
In addition, necroptosis, a relatively novel programmed necrosis-like pathway
associated with TNF receptor activation, seems to be also present in the
pathogenesis of Crohn's disease and in specific animal models for intestinal
inflammation. This review attempts to cover new data related to cell death
mechanisms and inflammatory bowel diseases.
PMID- 25126551
TI - Video game addiction in gambling disorder: clinical, psychopathological, and
personality correlates.
AB - OBJECTIVE: We studied the prevalences of video game use (VGU) and addiction (VGA)
in gambling disorder (GD) patients and compared them with subjects with non-video
game use (non-VGU) in relation to their gambling behavior, psychopathology, and
personality characteristics. METHOD: A sample of 193 GD patients (121 non-VGU, 43
VGU, and 29 VGA) consecutively admitted to our pathological gambling unit
participated in the study. Assessment. Measures included the video game
dependency test (VDT), symptom checklist-90-revised, and the temperament and
character inventory-revised, as well as a number of other GD indices. RESULTS: In
GD, the observed prevalence of VG (use or addiction) was 37.3% (95% CI :30.7% /
44.3),VGU 22.3% (95% CI :17.0% / 28.7), and VGA 15% (95% CI :10.7% / 20.7).
Orthogonal polynomial contrast into logistic regression showed positive linear
trends for VG level and GD severity and other measures of general
psychopathology. After structural equation modeling, higher VG total scores were
associated with younger age, general psychopathology, and specific personality
traits, but not with GD severity. Patients' sex and age were involved in the
mediational pathways between personality traits and VG impairment. CONCLUSIONS:
GD patients with VG are younger and present more dysfunctional personality
traits, and more general psychopathology. The presence of VG did not affect the
severity of GD.
PMID- 25126552
TI - Role of nutrient-sensing signals in the pathogenesis of diabetic nephropathy.
AB - Diabetic nephropathy is the leading cause of end-stage renal disease worldwide.
The multipronged drug approach still fails to fully prevent the onset and
progression of diabetic nephropathy. Therefore, a new therapeutic target to
improve the prognosis of diabetic nephropathy is urgently required. Nutrient
sensing signals and their related intracellular machinery have evolved to combat
prolonged periods of starvation in mammals; and these systems are conserved in
the kidney. Recent studies have suggested that the activity of three nutrient
sensing signals, mTORC1, AMPK, and Sirt1, is altered in the diabetic kidney.
Furthermore, autophagy activity, which is regulated by the above-mentioned
nutrient-sensing signals, is also altered in both podocytes and proximal tubular
cells under diabetic conditions. Under diabetic conditions, an altered
nutritional state owing to nutrient excess may disturb cellular homeostasis
regulated by nutrient-responsible systems, leading to exacerbation of organelle
dysfunction and diabetic nephropathy. In this review, we discuss new findings
showing relationships between nutrient-sensing signals, autophagy, and diabetic
nephropathy and suggest the therapeutic potential of nutrient-sensing signals in
diabetic nephropathy.
PMID- 25126553
TI - Protection of coronary endothelial function during cardiac surgery: potential of
targeting endothelial ion channels in cardioprotection.
AB - Vascular endothelium plays a critical role in the control of blood flow by
producing vasoactive factors to regulate vascular tone. Ion channels, in
particular, K(+) channels and Ca(2+)-permeable channels in endothelial cells, are
essential to the production and function of endothelium-derived vasoactive
factors. Impairment of coronary endothelial function occurs in open heart surgery
that may result in reduction of coronary blood flow and thus in an inadequate
myocardial perfusion. Hyperkalemic exposure and concurrent ischemia-reperfusion
during cardioplegic intervention compromise NO and EDHF-mediated function and the
impairment involves alterations of K(+) channels, that is, KATP and KCa, and
Ca(2+)-permeable TRP channels in endothelial cells. Pharmacological modulation of
these channels during ischemia-reperfusion and hyperkalemic exposure show
promising results on the preservation of NO and EDHF-mediated endothelial
function, which suggests the potential of targeting endothelial K(+) and TRP
channels for myocardial protection during cardiac surgery.
PMID- 25126554
TI - Next generation delivery system for proteins and genes of therapeutic purpose:
why and how?
AB - Proteins and genes of therapeutic interests in conjunction with different
delivery systems are growing towards new heights. "Next generation delivery
systems" may provide more efficient platform for delivery of proteins and genes.
In the present review, snapshots about the benefits of proteins or gene therapy,
general procedures for therapeutic protein or gene delivery system, and different
next generation delivery system such as liposome, PEGylation, HESylation, and
nanoparticle based delivery have been depicted with their detailed explanation.
PMID- 25126556
TI - Identifying the gene signatures from gene-pathway bipartite network guarantees
the robust model performance on predicting the cancer prognosis.
AB - For the purpose of improving the prediction of cancer prognosis in the clinical
researches, various algorithms have been developed to construct the predictive
models with the gene signatures detected by DNA microarrays. Due to the
heterogeneity of the clinical samples, the list of differentially expressed genes
(DEGs) generated by the statistical methods or the machine learning algorithms
often involves a number of false positive genes, which are not associated with
the phenotypic differences between the compared clinical conditions, and
subsequently impacts the reliability of the predictive models. In this study, we
proposed a strategy, which combined the statistical algorithm with the gene
pathway bipartite networks, to generate the reliable lists of cancer-related DEGs
and constructed the models by using support vector machine for predicting the
prognosis of three types of cancers, namely, breast cancer, acute myeloma
leukemia, and glioblastoma. Our results demonstrated that, combined with the gene
pathway bipartite networks, our proposed strategy can efficiently generate the
reliable cancer-related DEG lists for constructing the predictive models. In
addition, the model performance in the swap analysis was similar to that in the
original analysis, indicating the robustness of the models in predicting the
cancer outcomes.
PMID- 25126555
TI - Polymorphisms at amino acid residues 141 and 154 influence conformational
variation in ovine PrP.
AB - Polymorphisms in ovine PrP at amino acid residues 141 and 154 are associated with
susceptibility to ovine prion disease: Leu141Arg154 with classical scrapie and
Phe141Arg154 and Leu141His154 with atypical scrapie. Classical scrapie is
naturally transmissible between sheep, whereas this may not be the case with
atypical scrapie. Critical amino acid residues will determine the range or
stability of structural changes within the ovine prion protein or its functional
interaction with potential cofactors, during conversion of PrPC to PrPSc in these
different forms of scrapie disease. Here we computationally identified that
regions of ovine PrP, including those near amino acid residues 141 and 154,
displayed more conservation than expected based on local structural environment.
Molecular dynamics simulations showed these conserved regions of ovine PrP
displayed genotypic differences in conformational repertoire and amino acid side
chain interactions. Significantly, Leu141Arg154 PrP adopted an extended beta
sheet arrangement in the N-terminal palindromic region more frequently than the
Phe141Arg154 and Leu141His154 variants. We supported these computational
observations experimentally using circular dichroism spectroscopy and
immunobiochemical studies on ovine recombinant PrP. Collectively, our
observations show amino acid residues 141 and 154 influence secondary structure
and conformational change in ovine PrP that may correlate with different forms of
scrapie.
PMID- 25126557
TI - Antiulcerogenic potential activity of free and nanoencapsulated Passiflora
serratodigitata L. extracts.
AB - This paper provides evidence that the leaves and stem of Passiflora
serratodigitata L. dry crude extract (DCE), ethylacetate fraction (EAF), and
residual water fraction show potential antiulcerogenic activity. Interestingly,
the polymeric nanocapsule loaded with EAF had 10-fold more activity than the free
EAF. Furthermore, the polymer nanoparticles provided homogeneous colloidal drug
delivery systems and allowed overcoming challenges such as poor aqueous
solubility as well as the physical-chemical instability of the organic extract,
which presented 90% (w/w) of the flavonoid content. The entrapment efficiency of
the total flavonoid was 90.6 +/- 2.5% (w/v) for the DCE and 79.9 +/- 2.7% (w/v)
for the EAF. This study shows that nanoencapsulation improves both the
physicochemical properties and the efficacy of the herbal formulations.
Therefore, free and encapsulated extracts have the potential to be suitable drug
design candidates for the therapeutic management of ulcer.
PMID- 25126558
TI - Microbiota in healthy skin and in atopic eczema.
AB - The Italian interest group (IG) on atopic eczema and urticaria is member of the
Italian Society of Allergology and Immunology. The aim of our IG is to provide a
platform for scientists, clinicians, and experts. In this review we discuss the
role of skin microbiota not only in healthy skin but also in skin suffering from
atopic dermatitis (AD). A Medline and Embase search was conducted for studies
evaluating the role of skin microbiota. We examine microbiota composition and its
development within days after birth; we describe the role of specific groups of
microorganisms that colonize distinct anatomical niches and the biology and
clinical relevance of antimicrobial peptides expressed in the skin. Specific AD
disease states are characterized by concurrent and anticorrelated shifts in
microbial diversity and proportion of Staphylococcus. These organisms may protect
the host, defining them not as simple symbiotic microbes but rather as
mutualistic microbes. These findings reveal links between microbial communities
and inflammatory diseases such as AD and provide novel insights into global
shifts of bacteria relevant to disease progression and treatment. This review
also highlights recent observations on the importance of innate immune systems
and the relationship with normal skin microflora for the maintenance of healthy
skin.
PMID- 25126559
TI - Multiparametric MRI in biopsy guidance for prostate cancer: fusion-guided.
AB - Prostate cancer (PCa) is the most common solid-organ malignancy among American
men and the second most deadly. Current guidelines recommend a 12-core systematic
biopsy following the finding of an elevated serum prostate-specific antigen
(PSA). However, this strategy fails to detect an unacceptably high percentage of
clinically significant cancers, leading researchers to develop new, innovative
methods to improve the effectiveness of prostate biopsies. Multiparametric-MRI
(MP-MRI) has emerged as a promising instrument in identifying suspicious regions
within the prostate that require special attention on subsequent biopsy. Fusion
platforms, which incorporate the MP-MRI into the biopsy itself and provide active
targets within real-time imaging, have shown encouraging results in improving the
detection rate of significant cancer. Broader applications of this technology,
including MRI-guided focal therapy for prostate cancer, are in early phase
trials.
PMID- 25126560
TI - Aesthetic evaluation of the nasolabial region in children with unilateral cleft
lip and palate comparing expert versus nonexperience health professionals.
AB - Esthetic evaluation of cleft lip and palate rehabilitation outcomes may assist in
the determination of new surgical interventions and aid in reevaluation of
treatment protocols. Our objective was to compare esthetics assessments of the
nasolabial region in children with a unilateral cleft lip and palate between
healthcare professionals who were experienced in the treatment of cleft lip and
palate and those who were inexperienced. The study group included 55 patients
between 6 and 12 years of age who had already undergone primary reconstructive
surgery for unilateral cleft lip. Standardized digital photographs were obtained,
and the esthetic features of the nose, lip, and nasolabial region were evaluated.
We used only cropped photographic images in the assessments of healthcare
professionals with and without experience in cleft lip and palate. Interrater
analysis revealed highly reliable assessments made by both the experienced and
inexperienced professionals. There was no statistically significant difference in
the esthetic attractiveness of the lip and nose between the experienced and
inexperienced professionals. Compared with the inexperienced professionals, the
experienced professional evaluators showed higher satisfaction with the esthetic
appearance of the nasolabial region; however, no difference was observed in the
analysis of the lip or nose alone.
PMID- 25126562
TI - A novel promising strain of Trichoderma evansii (WF-3) for extracellular alpha
galactosidase production by utilizing different carbon sources under optimized
culture conditions.
AB - A potential fungal strain of Trichoderma sp. (WF-3) was isolated and selected for
the production of alpha-galactosidase. Optimum conditions for mycelial growth and
enzyme induction were determined. Basal media selected for the growth of fungal
isolate containing different carbon sources like guar gum (GG), soya bean meal
(SM), and wheat straw (WS) and combinations of these carbon substrates with basic
sugars like galactose and sucrose were used to monitor their effects on alpha
galactosidase production. The results of this study indicated that galactose and
sucrose enhanced the enzyme activity in guar gum (GG) and wheat straw (WS).
Maximum alpha-galactosidase production (213.63 U mL(-1)) was obtained when the
basic medium containing GG is supplemented with galactose (5 mg/mL). However, the
presence of galactose and sucrose alone in the growth media shows no effect. Soya
meal alone was able to support T. evansii to produce maximum enzyme activity
(170.36 U mL(-1)). The incubation time, temperature, and pH for the maximum
enzyme synthesis were found to be 120 h (5 days), 28 degrees C, and 4.5-5.5,
respectively. All the carbon sources tested exhibited maximum enzyme production
at 10 mg/mL concentration. Among the metal ions tested, Hg was found to be the
strongest inhibitor of the enzyme. Among the chelators, EDTA acted as stronger
inhibitor than succinic acid.
PMID- 25126561
TI - The roles of CD73 in cancer.
AB - Purinergic signaling has emerged as an important player in cancer progression and
is regulated by a series of nucleotidases. Among the enzyme cascade, CD73, which
catelyzes AMP breakdown to adenosine, has been found to be overexpressed in many
types of cancer. Various factors and mechanisms are employed to regulate
expression of CD73. Accumulating studies have shown that CD73 is a key regulatory
molecule of cancer cells proliferation, migration and invasion in vitro, tumor
angiogenesis, and tumor immune escape in vivo. With such important roles in
cancer, CD73 has become an appealing therapy target. Recent evidences in mice
models demonstrated that targeted blockade of CD73 could be a favorable
therapeutic approach for cancer patients in the future. In this review, we will
summarize the multiple roles of CD73 in cancer development, including its
clinical significance, its promotive effects on tumor growth, metastasis, and
angiogenesis, and its suppressive effects on immune response, regulatory
mechanisms of CD73 expression, and current situation of anti-CD73 cancer therapy.
PMID- 25126563
TI - Modulation of TLR 3, 7 and 8 expressions in HCV genotype 3 infected individuals:
potential correlations of pathogenesis and spontaneous clearance.
AB - BACKGROUND: Hepatitis C virus is the major cause of chronic hepatitis worldwide
which finally leads to the development of hepatocellular carcinoma. Toll like
receptors (TLRs) play an important role in the course of many viral infections,
but the role of TLRs in HCV pathogenesis has not been well elucidated so far.
OBJECTIVE: The aim of this study was to analyse the mRNA expression of TLRs 3, 7,
and 8 in different stages of HCV infection including chronic, cirrhosis,
interferon treated resolved, and relapsed cases. METHODOLOGY: Total RNA from
whole blood was extracted and mRNA expression of TLRs 3, 7, and 8 genes was
analyzed by quantitative real-time RT-PCR using beta-Actin gene as an internal
control. RESULTS: This study consisted of 100 HCV infected individuals and twenty
healthy controls. TLR 3 expression was found to be significantly elevated in
individuals who had spontaneously cleared the virus (p < 0.001), whereas TLR 7
was found to be 3.26 times more elevated in patients with cirrhosis of liver. In
IFN induced individuals, TLR 8 expression levels were found to be 2.28-fold
elevated as compared to control population. CONCLUSION: TLRs 3, 7, and 8 are
prime biomarker candidates for HCV infection mRNA expression analysis which might
improve current therapeutic approaches.
PMID- 25126565
TI - Definition of metrics to evaluate cochlear array insertion forces performed with
forceps, insertion tool, or motorized tool in temporal bone specimens.
AB - INTRODUCTION: In order to achieve a minimal trauma to the inner ear structures
during array insertion, it would be suitable to control insertion forces. The aim
of this work was to compare the insertion forces of an array insertion into
anatomical specimens with three different insertion techniques: with forceps,
with a commercial tool, and with a motorized tool. MATERIALS AND METHODS:
Temporal bones have been mounted on a 6-axis force sensor to record insertion
forces. Each temporal bone has been inserted, with a lateral wall electrode
array, in random order, with each of the 3 techniques. RESULTS: Forceps manual
and commercial tool insertions generated multiple jerks during whole length
insertion related to fits and starts. On the contrary, insertion force with the
motorized tool only rose at the end of the insertion. Overall force momentum was
1.16 +/- 0.505 N (mean +/- SD, n = 10), 1.337 +/- 0.408 N (n = 8), and 1.573 +/-
0.764 N (n = 8) for manual insertion with forceps and commercial and motorized
tools, respectively. CONCLUSION: Considering force momentum, no difference
between the three techniques was observed. Nevertheless, a more predictable force
profile could be observed with the motorized tool with a smoother rise of
insertion forces.
PMID- 25126567
TI - Skin cancer, irradiation, and sunspots: the solar cycle effect.
AB - Skin cancer is diagnosed in more than 2 million individuals annually in the
United States. It is strongly associated with ultraviolet exposure, with melanoma
risk doubling after five or more sunburns. Solar activity, characterized by
features such as irradiance and sunspots, undergoes an 11-year solar cycle. This
fingerprint frequency accounts for relatively small variation on Earth when
compared to other uncorrelated time scales such as daily and seasonal cycles.
Kolmogorov-Zurbenko filters, applied to the solar cycle and skin cancer data,
separate the components of different time scales to detect weaker long term
signals and investigate the relationships between long term trends. Analyses of
crosscorrelations reveal epidemiologically consistent latencies between variables
which can then be used for regression analysis to calculate a coefficient of
influence. This method reveals that strong numerical associations, with
correlations >0.5, exist between these small but distinct long term trends in the
solar cycle and skin cancer. This improves modeling skin cancer trends on long
time scales despite the stronger variation in other time scales and the
destructive presence of noise.
PMID- 25126566
TI - KPG index versus OPG measurements: a comparison between 3D and 2D methods in
predicting treatment duration and difficulty level for patients with impacted
maxillary canines.
AB - AIM: The aim of this study was to test the agreement between orthopantomography
(OPG) based 2D measurements and the KPG index, a new index based on 3D Cone Beam
Computed Tomography (CBCT) images, in predicting orthodontic treatment duration
and difficulty level of impacted maxillary canines. MATERIALS AND METHODS: OPG
and CBCT images of 105 impacted canines were independently scored by three
orthodontists at t 0 and after 1 month (t 1), using the KPG index and the
following 2D methods: distance from cusp tip and occlusal plane, cusp tip
position in relation to the lateral incisor, and canine inclination. Pearson's
coefficients were used to evaluate the degree of agreement and the chi(2) with
Yates correction test was used to assess the independence between them. RESULTS:
Inter- and intrarater reliability were higher with KPG compared to 2D methods.
Pearson's coefficients showed a statistically significant association between all
the indexes, while the chi(2) with Yates correction test resulted in a
statistically significant rejection of independency only for one 2D index.
CONCLUSIONS: 2D indexes for predicting impacted maxillary canines treatment
duration and difficulty sometimes are discordant; a 3D index like the KPG index
could be useful in solving these conflicts.
PMID- 25126568
TI - Depletion of arginine by recombinant arginine deiminase induces nNOS-activated
neurotoxicity in neuroblastoma cells.
AB - The abnormal regulation of inducible nitric oxide synthase (iNOS) and neuronal
nitric oxide synthase (nNOS) is associated with neurodegenerative disorders.
Recombinant arginine deiminase (rADI) is a selective NO modulator of iNOS and
eNOS in endothelial cells, and it also exhibits neuroprotective activity in an
iNOS-induced neuron-microglia coculture system. However, the effect of rADI on
nNOS remains unknown. Addressing this issue is important for evaluating the
potential application of rADI in neurodegenerative diseases. SH-SY5Y cells were
treated with N-methyl-D-aspartic acid (NMDA) to activate nNOS. NMDA increased NO
production by 39.7 +/- 3.9% via nNOS under arginine-containing conditions, but
there was no significant increase in both arginine-free and rADI pretreated
arginine-containing (citrulline) buffer. Subsequently, neither NMDA nor rADI
alone caused cytotoxicity, whereas cotreatment with NMDA and rADI resulted in
dissipation of the cell mitochondrial membrane potential and decreased cell
viability. The mechanism of rADI cytotoxicity in the presence of NMDA is caused
by the inhibition of NO production via nNOS mediated by the NMDA receptor, which
was abolished when extracellular arginine was absent, even in the presence of
citrulline. rADI not only reduced NO production but also caused cellular toxicity
in nNOS-activated SH-SY5Y cells, suggesting a dual role for rADI in NOS-mediated
neurotoxicity.
PMID- 25126570
TI - PPI network analysis of mRNA expression profile of ezrin knockdown in esophageal
squamous cell carcinoma.
AB - Ezrin, coding protein EZR which cross-links actin filaments, overexpresses and
involves invasion, metastasis, and poor prognosis in various cancers including
esophageal squamous cell carcinoma (ESCC). In our previous study, Ezrin was knock
down and analyzed by mRNA expression profile which has not been fully mined. In
this study, we applied protein-protein interactions (PPI) network knowledge and
methods to explore our understanding of these differentially expressed genes
(DEGs). PPI subnetworks showed that hundreds of DEGs interact with thousands of
other proteins. Subcellular localization analyses found that the DEGs and their
directly or indirectly interacting proteins distribute in multiple layers, which
was applied to analyze the shortest paths between EZR and other DEGs. Gene
ontology annotation generated a functional annotation map and found hundreds of
significant terms, especially those associated with cytoskeleton organization of
Ezrin protein, such as "cytoskeleton organization," "regulation of actin filament
based process," and "regulation of actin cytoskeleton organization." The
algorithm of Random Walk with Restart was applied to prioritize the DEGs and
identified several cancer related DEGs ranked closest to EZR. These analyses
based on PPI network have greatly expanded our comprehension of the mRNA
expression profile of Ezrin knockdown for future examination of the roles and
mechanisms of Ezrin.
PMID- 25126571
TI - Mass spectrometry based proteomic analysis of salivary glands of urban malaria
vector Anopheles stephensi.
AB - Salivary gland proteins of Anopheles mosquitoes offer attractive targets to
understand interactions with sporozoites, blood feeding behavior, homeostasis,
and immunological evaluation of malaria vectors and parasite interactions. To
date limited studies have been carried out to elucidate salivary proteins of An.
stephensi salivary glands. The aim of the present study was to provide detailed
analytical attributives of functional salivary gland proteins of urban malaria
vector An. stephensi. A proteomic approach combining one-dimensional
electrophoresis (1DE), ion trap liquid chromatography mass spectrometry
(LC/MS/MS), and computational bioinformatic analysis was adopted to provide the
first direct insight into identification and functional characterization of known
salivary proteins and novel salivary proteins of An. stephensi. Computational
studies by online servers, namely, MASCOT and OMSSA algorithms, identified a
total of 36 known salivary proteins and 123 novel proteins analysed by LC/MS/MS.
This first report describes a baseline proteomic catalogue of 159 salivary
proteins belonging to various categories of signal transduction, regulation of
blood coagulation cascade, and various immune and energy pathways of An.
stephensi sialotranscriptome by mass spectrometry. Our results may serve as basis
to provide a putative functional role of proteins in concept of blood feeding,
biting behavior, and other aspects of vector-parasite host interactions for
parasite development in anopheline mosquitoes.
PMID- 25126569
TI - Collagen VI and hyaluronan: the common role in breast cancer.
AB - Collagen VI and hyaluronan are widely distributed extracellular matrix
macromolecules that play a crucial role in tissue development and are highly
expressed in cancers. Both hyaluronan and collagen VI are upregulated in breast
cancer, generating a microenvironment that promotes tumour progression and
metastasis. A growing number of studies show that these two molecules are
involved in inflammation and angiogenesis by recruiting macrophages and
endothelial cells, respectively. Additionally, collagen VI induces epithelial
mesenchymal transition that is correlated to increased synthesis of hyaluronan in
mammary cells. Hyaluronan has also a specific role in cellular functions that
depends mainly on the size of the polymer, whereas the effect of collagen VI in
tumour progression may be the result of the intact molecule or the C5 peptide of
alpha3(VI) chain, known as endotrophin. Collectively, these findings strongly
support the parallel role of these molecules in tumour progression and suggest
that they may be used as prognostic factors for the breast cancer treatment.
PMID- 25126572
TI - Metabolic modeling of common Escherichia coli strains in human gut microbiome.
AB - The recent high-throughput sequencing has enabled the composition of Escherichia
coli strains in the human microbial community to be profiled en masse. However,
there are two challenges to address: (1) exploring the genetic differences
between E. coli strains in human gut and (2) dynamic responses of E. coli to
diverse stress conditions. As a result, we investigated the E. coli strains in
human gut microbiome using deep sequencing data and reconstructed genome-wide
metabolic networks for the three most common E. coli strains, including E. coli
HS, UTI89, and CFT073. The metabolic models show obvious strain-specific
characteristics, both in network contents and in behaviors. We predicted optimal
biomass production for three models on four different carbon sources (acetate,
ethanol, glucose, and succinate) and found that these stress-associated genes
were involved in host-microbial interactions and increased in human obesity.
Besides, it shows that the growth rates are similar among the models, but the
flux distributions are different, even in E. coli core reactions. The
correlations between human diabetes-associated metabolic reactions in the E. coli
models were also predicted. The study provides a systems perspective on E. coli
strains in human gut microbiome and will be helpful in integrating diverse data
sources in the following study.
PMID- 25126564
TI - Human genetic disorders and knockout mice deficient in glycosaminoglycan.
AB - Glycosaminoglycans (GAGs) are constructed through the stepwise addition of
respective monosaccharides by various glycosyltransferases and maturated by
epimerases and sulfotransferases. The structural diversity of GAG
polysaccharides, including their sulfation patterns and sequential arrangements,
is essential for a wide range of biological activities such as cell signaling,
cell proliferation, tissue morphogenesis, and interactions with various growth
factors. Studies using knockout mice of enzymes responsible for the biosynthesis
of the GAG side chains of proteoglycans have revealed their physiological
functions. Furthermore, mutations in the human genes encoding
glycosyltransferases, sulfotransferases, and related enzymes responsible for the
biosynthesis of GAGs cause a number of genetic disorders including
chondrodysplasia, spondyloepiphyseal dysplasia, and Ehlers-Danlos syndromes. This
review focused on the increasing number of glycobiological studies on knockout
mice and genetic diseases caused by disturbances in the biosynthetic enzymes for
GAGs.
PMID- 25126573
TI - First record of isolation and characterization of methicillin resistant
Staphylococcus lugdunensis from clinical samples in Iraq.
AB - This study was conducted to determine the frequency of Staphylococcus lugdunensis
in different clinical samples. Out of 690 clinical samples, a total of 178
coagulase negative staphylococci (CoNS) isolates were recovered. CoNS were
identified as 10 different species; 22 isolates belonged to Staphylococcus
lugdunensis. Two specific genes for S. lugdunensis were used (tanA gene and fbl
gene) to confirm identification. Both of these specific genes were detected in 15
(68.1%) of 22 isolates that were identified phenotypically. The results of
oxacillin MIC showed that 7 of the 15 (46.6%) S. lugdunensis isolates were
oxacillin resistant. The antibiotic susceptibility testing against 16 antibiotics
showed that resistance rates were variable towards these antibiotics. Eight of
fifteen S. lugdunensis isolates (53.3%) were beta-lactamase producer. Results of
molecular detection of mecA gene found that mecA gene was detected in 6 (40%) of
15 S. lugdunensis. All of these 6 isolates (S1, S2, S3, S4, S5, and S6) were
resistant to oxacillin. One isolate (S7) was resistant to oxacillin but mecA was
not detected in this isolate. This study is a first record of isolation and
characterization of methicillin resistant S. lugdunensis (MRSL) from clinical
samples in Iraq.
PMID- 25126574
TI - Blood monocyte subsets and selected cardiovascular risk markers in rheumatoid
arthritis of short duration in relation to disease activity.
AB - OBJECTIVES: To evaluate blood monocyte subsets and functional monocyte properties
in patients with rheumatoid arthritis (RA) of short duration in the context of
cardiovascular (CV) risk and disease activity. METHODS: We studied conventional
markers of CV risk, intima media thickness (IMT), and blood monocyte subsets in
27 patients aged 41 +/- 10 years with RA of short duration (median 12 months) and
22 healthy controls. The RA subjects were divided into low (DAS28: 2.6-5.1) and
high (DAS28 > 5.1) disease activity. RESULTS: RA patients exhibited increased
levels of intermediate (CD14(++)CD16(+)) monocytes with decreased CD45RA
expression compared to controls, increased counts of classical (CD14(++)CD16(-))
monocytes, and decreased percentages of nonclassical (CD14(+)CD16(++)) monocytes.
Patients with high disease activity had lower HLA DR expression on classical
monocytes compared to low disease activity patients. There were no differences in
monocyte subsets between subjects with DAS > 5.1 and DAS <= 5.1. There were no
significant intergroup differences in IMT and the majority of classical CV risk
factors. CONCLUSIONS: Patients with RA of short duration show alteration in
peripheral blood monocyte subsets despite the fact that there is no evidence of
subclinical atherosclerosis. Disease activity assessed with DAS28 was associated
with impaired functional properties but not with a shift in monocyte
subpopulations.
PMID- 25126576
TI - Biomechanical analysis of force distribution in human finger extensor mechanisms.
AB - The complexities of the function and structure of human fingers have long been
recognised. The in vivo forces in the human finger tendon network during
different activities are critical information for clinical diagnosis, surgical
treatment, prosthetic finger design, and biomimetic hand development. In this
study, we propose a novel method for in vivo force estimation for the finger
tendon network by combining a three-dimensional motion analysis technique and a
novel biomechanical tendon network model. The extensor mechanism of a human index
finger is represented by an interconnected tendinous network moving around the
phalanx's dorsum. A novel analytical approach based on the "Principle of Minimum
Total Potential Energy" is used to calculate the forces and deformations
throughout the tendon network of the extensor mechanism when subjected to an
external load and with the finger posture defined by measurement data. The
predicted deformations and forces in the tendon network are in broad agreement
with the results obtained by previous experimental in vitro studies. The proposed
methodology provides a promising tool for investigating the biomechanical
function of complex interconnected tendon networks in vivo.
PMID- 25126575
TI - Store-operated Ca2+ entry does not control proliferation in primary cultures of
human metastatic renal cellular carcinoma.
AB - Store-operated Ca(2+) entry (SOCE) is activated following depletion of the
inositol-1,4,5-trisphosphate (InsP3)-sensitive Ca(2+) pool to regulate
proliferation in immortalized cell lines established from either primary or
metastatic lesions. The molecular nature of SOCE may involve both Stim1, which
senses Ca(2+) levels within the endoplasmic reticulum (ER) Ca(2+) reservoir, and
a number of a Ca(2+)-permeable channels on the plasma membrane, including Orai1,
Orai3, and members of the canonical transient receptor (TRPC1-7) family of ion
channels. The present study was undertaken to assess whether SOCE is expressed
and controls proliferation in primary cultures isolated from secondary lesions of
heavily pretreated metastatic renal cell carcinoma (mRCC) patients. SOCE was
induced following pharmacological depletion of the ER Ca(2+) store, but not by
InsP3-dependent Ca(2+) release. Metastatic RCC cells express Stim1-2, Orai1-3,
and TRPC1-7 transcripts and proteins. In these cells, SOCE was insensitive to BTP
2, 10 uM Gd(3+) and Pyr6, while it was inhibited by 100 uM Gd(3+), 2-APB, and
carboxyamidotriazole (CAI). Neither Gd(3+) nor 2-APB or CAI impaired mRCC cell
proliferation. Consistently, no detectable Ca(2+) signal was elicited by growth
factor stimulation. Therefore, a functional SOCE is expressed but does not
control proliferation of mRCC cells isolated from patients resistant to
multikinase inhibitors.
PMID- 25126578
TI - Movement type prediction before its onset using signals from prefrontal area: an
electrocorticography study.
AB - Power changes in specific frequency bands are typical brain responses during
motor planning or preparation. Many studies have demonstrated that, in addition
to the premotor, supplementary motor, and primary sensorimotor areas, the
prefrontal area contributes to generating such responses. However, most brain
computer interface (BCI) studies have focused on the primary sensorimotor area
and have estimated movements using postonset period brain signals. Our aim was to
determine whether the prefrontal area could contribute to the prediction of
voluntary movement types before movement onset. In our study,
electrocorticography (ECoG) was recorded from six epilepsy patients while
performing two self-paced tasks: hand grasping and elbow flexion. The prefrontal
area was sufficient to allow classification of different movements through the
area's premovement signals (-2.0 s to 0 s) in four subjects. The most pronounced
power difference frequency band was the beta band (13-30 Hz). The movement
prediction rate during single trial estimation averaged 74% across the six
subjects. Our results suggest that premovement signals in the prefrontal area are
useful in distinguishing different movement tasks and that the beta band is the
most informative for prediction of movement type before movement onset.
PMID- 25126577
TI - MicroRNA expression in salivary supernatant of patients with pancreatic cancer
and its relationship with ZHENG.
AB - In traditional Chinese medicine (TCM), diagnosis and prescriptions are based on
the signs and symptoms which are recognized as ZHENG. The cornerstone of TCM is
to differentially treat one ZHENG from others, which is also known as syndrome
differentiation, and this relies on the gathering of clinical information through
inspection, auscultation and olfaction, inquiry, and palpation. However, the
biomolecular basis of the ZHENG remains unclear. In this study, the expressions
of 384 cancer-related miRNAs in salivary supernatant of patients with pancreatic
cancer were assessed by miRNA polymerase chain reaction (PCR) array, and the
different expression patterns of miRNA in three different groups of ZHENG were
studied with use of real-time quantitative PCR (qRT-PCR). Some miRNAs were found
to be specifically expressed in some ZHENGs, for instance, miR-17, miR-21, and
miR-181b in Shi-Re ZHENG and miR-196a in Pi-Xu ZHENG. This indicates that these
miRNAs may play important roles in different ZHENG condition. Therefore, this
study to some extent revealed the molecular basis of TCM ZHENG in pancreatic
cancer.
PMID- 25126579
TI - The definition of a prolonged intensive care unit stay for spontaneous
intracerebral hemorrhage patients: an application with national health insurance
research database.
AB - INTRODUCTION: Length of stay (LOS) in the intensive care unit (ICU) of
spontaneous intracerebral hemorrhage (sICH) patients is one of the most important
issues. The disease severity, psychosocial factors, and institutional factors
will influence the length of ICU stay. This study is used in the Taiwan National
Health Insurance Research Database (NHIRD) to define the threshold of a prolonged
ICU stay in sICH patients. METHODS: This research collected the demographic data
of sICH patients in the NHIRD from 2005 to 2009. The threshold of prolonged ICU
stay was calculated using change point analysis. RESULTS: There were 1599 sICH
patients included. A prolonged ICU stay was defined as being equal to or longer
than 10 days. There were 436 prolonged ICU stay cases and 1163 nonprolonged
cases. CONCLUSION: This study showed that the threshold of a prolonged ICU stay
is a good indicator of hospital utilization in ICH patients. Different hospitals
have their own different care strategies that can be identified with a prolonged
ICU stay. This indicator can be improved using quality control methods such as
complications prevention and efficiency of ICU bed management. Patients' stay in
ICUs and in hospitals will be shorter if integrated care systems are established.
PMID- 25126580
TI - Using ecological momentary assessment to evaluate current physical activity.
AB - OBJECTIVE: The purpose of this study was to assess the value of ecological
momentary assessment in evaluating physical activity among children, adolescents,
and adults. It also determines whether ecological momentary assessment fulfills
the criteria of validity, reliability, objectivity, norms, and standardization
applied to the tools used for the evaluation of physical activity. METHODS: The
EBSCO-CINHAL, Medline, PsycINFO, PubMed, and SPORTDiscuss databases were reviewed
in December 2012 for articles associated with EMA. RESULTS: Of the 20 articles
examined, half (10) used electronic methods for data collection, although various
methods were used, ranging from pen and paper to smartphone applications. Ten
studies used objective monitoring equipment. Nineteen studies were performed over
4 days. While the validity of the EMA method was discussed in 18 studies, only
four found it to be objective. In all cases, the EMA procedures were precisely
documented and confirmed to be feasible. CONCLUSIONS: Ecological momentary
assessment is a valid, reliable, and feasible approach to evaluate activity and
sedentary behavior. Researchers should be aware that while ecological momentary
assessment offers many benefits, it simultaneously imposes many limitations which
should be considered when studying physical activity.
PMID- 25126581
TI - Patient outcomes following subarachnoid hemorrhage between the medical center and
regional hospital: whether all patients should be transferred to medical centers.
AB - Subarachnoid hemorrhage (SAH) is a critical illness that may result in patient
mortality or morbidity. In this study, we investigated the outcomes of patients
treated in medical center and nonmedical center hospitals and the relationship
between such outcomes and hospital and surgeon volume. Patient data were
abstracted from the National Health Insurance Research Database of Taiwan in the
Longitudinal Health Insurance Database 2000, which contains all claims data of 1
million beneficiaries randomly selected in 2000. The International Classification
of Diseases, Ninth Revision, subarachnoid hemorrhage (430) was used for the
inclusion criteria. We identified 355 patients between 11 and 87 years of age who
had subarachnoid hemorrhage. Among them, 32.4% (115/355) were men. The median
Charlson comorbidity index (CCI) score was 1.3 (SD +/- 0.6). Unadjusted logistic
regression analysis demonstrated that low mortality was associated with high
hospital volume (OR = 3.21; 95% CI: 1.18-8.77). In this study, we found no
statistical significances of mortality, LOS, and total charges between medical
centers and nonmedical center hospitals. Patient mortality was associated with
hospital volume. Nonmedical center hospitals could achieve resource use and
outcomes similar to those of medical centers with sufficient volume.
PMID- 25126582
TI - Ethical and legal implications of elective ventilation and organ transplantation:
"medicalization" of dying versus medical mission.
AB - A critical controversy surrounds the type of allowable interventions to be
carried out in patients who are potential organ donors, in an attempt to improve
organ perfusion and successful transplantation. The main goal is to transplant an
organ in conditions as close as possible to its physiological live state.
"Elective ventilation" (EV), that is, the use of ventilation for the sole purpose
of retrieving the organs of patients close to death, is an option which offsets
the shortage of organ donation. We have analyzed the legal context of the dying
process of the organ donor and the feasibility of EV in the Italian context.
There is no legal framework regulating the practice of EV, neither is any real
information given to the general public. A public debate has yet to be initiated.
In the Italian cultural and legislative scenario, we believe that, under some
circumstances (i.e., the expressed wishes of the patient, even in the form of
advance directives), the use of EV does not violate the principle of beneficence.
We believe that the crux of the matter lies in the need to explore the real
determination and will of the patient and his/her orientation towards the
specific aim of organ donation.
PMID- 25126584
TI - Potential and limitation of HLA-based banking of human pluripotent stem cells for
cell therapy.
AB - Great hopes have been placed on human pluripotent stem (hPS) cells for therapy.
Tissues or organs derived from hPS cells could be the best solution to cure many
different human diseases, especially those who do not respond to standard
medication or drugs, such as neurodegenerative diseases, heart failure, or
diabetes. The origin of hPS is critical and the idea of creating a bank of well
characterized hPS cells has emerged, like the one that already exists for cord
blood. However, the main obstacle in transplantation is the rejection of tissues
or organ by the receiver, due to the three main immunological barriers: the human
leukocyte antigen (HLA), the ABO blood group, and minor antigens. The problem
could be circumvented by using autologous stem cells, like induced pluripotent
stem (iPS) cells, derived directly from the patient. But iPS cells have
limitations, especially regarding the disease of the recipient and possible
difficulties to handle or prepare autologous iPS cells. Finally, reaching
standards of good clinical or manufacturing practices could be challenging. That
is why well-characterized and universal hPS cells could be a better solution. In
this review, we will discuss the interest and the feasibility to establish hPS
cells bank, as well as some economics and ethical issues.
PMID- 25126583
TI - Glioma-associated antigen HEATR1 induces functional cytotoxic T lymphocytes in
patients with glioma.
AB - A2B5+ glioblastoma (GBM) cells have glioma stem-like cell (GSC) properties that
are crucial to chemotherapy resistance and GBM relapse. T-cell-based antigens
derived from A2B5+ GBM cells provide important information for immunotherapy.
Here, we show that HEAT repeat containing 1 (HEATR1) expression in GBM tissues
was significantly higher than that in control brain tissues. Furthermore, HEATR1
expression in A2B5+ U87 cells was higher than that in A2B5-U87 cells (P = 0.016).
Six peptides of HEATR1 presented by HLA-A*02 were selected for testing of their
ability to induce T-cell responses in patients with GBM. When peripheral blood
mononuclear cells from healthy donors (n = 6) and patients with glioma (n = 33)
were stimulated with the peptide mixture, eight patients with malignant gliomas
had positive reactivity with a significantly increased number of responding T
cells. The peptides HEATR(1682-690), HEATR(11126-1134), and HEATR(1757-765) had
high affinity for binding to HLA-A*02:01 and a strong capacity to induce CTL
response. CTLs against HEATR1 peptides were capable of recognizing and lysing GBM
cells and GSCs. These data are the first to demonstrate that HEATR1 could induce
specific CTL responses targeting both GBM cells and GSCs, implicating that HEATR1
peptide-based immunotherapy could be a novel promising strategy for treating
patients with GBM.
PMID- 25126585
TI - Cellular factors targeting APCs to modulate adaptive T cell immunity.
AB - The fate of adaptive T cell immunity is determined by multiple cellular and
molecular factors, among which the cytokine milieu plays the most important role
in this process. Depending on the cytokines present during the initial T cell
activation, T cells become effector cells that produce different effector
molecules and execute adaptive immune functions. Studies thus far have primarily
focused on defining how these factors control T cell differentiation by targeting
T cells themselves. However, other non-T cells, particularly APCs, also express
receptors for the factors and are capable of responding to them. In this review,
we will discuss how APCs, by responding to those cytokines, influence T cell
differentiation and adaptive immunity.
PMID- 25126587
TI - The relevance of HLA sequencing in population genetics studies.
AB - Next generation sequencing (NGS) is currently being adapted by different
biotechnological platforms to the standard typing method for HLA polymorphism,
the huge diversity of which makes this initiative particularly challenging.
Boosting the molecular characterization of the HLA genes through efficient,
rapid, and low-cost technologies is expected to amplify the success of tissue
transplantation by enabling us to find donor-recipient matching for rare
phenotypes. But the application of NGS technologies to the molecular mapping of
the MHC region also anticipates essential changes in population genetic studies.
Huge amounts of HLA sequence data will be available in the next years for
different populations, with the potential to change our understanding of HLA
variation in humans. In this review, we first explain how HLA sequencing allows a
better assessment of the HLA diversity in human populations, taking also into
account the methodological difficulties it introduces at the statistical level;
secondly, we show how analyzing HLA sequence variation may improve our
comprehension of population genetic relationships by facilitating the
identification of demographic events that marked human evolution; finally, we
discuss the interest of both HLA and genome-wide sequencing and genotyping in
detecting functionally significant SNPs in the MHC region, the latter having also
contributed to the makeup of the HLA molecular diversity observed today.
PMID- 25126588
TI - Disease-Modifying Effect of Adiponectin in Model of alpha-Synucleinopathies.
AB - OBJECTIVE: Growing evidence suggests that neurodegenerative diseases are
associated with metabolic disorders, but the mechanisms are still unclear. Better
comprehension of this issue might provide a new strategy for treatment of
neurodegenerative diseases. We investigated possible roles of adiponectin (APN),
the anti-diabetes protein, in the pathogenesis of alpha-synucleinopathies.
METHODS: Using biochemical and histological methods, we investigated autopsy
brain of alpha-synucleinopathies including Parkinson's disease (PD) and dementia
with Lewy bodies (DLB), and analyzed the effects of APN in cellular and in mouse
models of alpha-synucleinopathies. RESULTS: We observed that APN is localized in
Lewy bodies derived from alpha-synucleinopathies such as Parkinson's disease and
dementia with Lewy bodies. In neuronal cells expressing alpha-synuclein (alphaS),
aggregation of alphaS was suppressed by treatment with recombinant APN in an
AdipoRI-AMP kinase pathway-dependent manner. Concomitantly, phosphorylation and
release of alphaS were significantly decreased by APN, suggesting that APN may be
antineurodegenerative. In transgenic mice expressing alphaS, both histopathology
and movement disorder were significantly improved by intranasal treatment with
globular APN when the treatment was initiated in the early stage of the disease.
In a mouse model, reduced levels of guanosine- and inosine- monophosphates, both
of which are potential stimulators of aggregation of alphaS, might partly
contribute to suppression of aggregation of alphaS by APN. INTERPRETATION: Taken
together, APN may suppress neurodegeneration through modification of the
metabolic pathway, and could possess a therapeutic potential against alpha
synucleinopathies.
PMID- 25126590
TI - Mini-review: perspective of the microbiome in the pathogenesis of urothelial
carcinoma.
AB - The microbiome is a new center of attention for studies on the pathogenesis of
human disease by focusing on the alterations of all microorganisms living in a
particular site or system of human body, referred as microbiota. Evidence
suggests that microbiota could contribute to the pathogenesis of a number of
chronic diseases, including cancers, both locally and remotely. Multiple
mechanisms have been proposed and/or proven for the microbiota's role in
tumorigenesis, such as via induction of chronic inflammation, genotoxicity,
bacterium-mediated cell proliferation, and activation of procarcinogens. Emerging
data suggest that indigenous microbiota in the urinary tract may play an
important role in the tumorigenesis of urothelial carcinoma, similar to other
tumors. Future studies are needed to adequately define the microbiota composition
and correlate its change with urothelial carcinoma.
PMID- 25126589
TI - Gaining the Upper Hand on Pulmonary Drug Delivery.
AB - Asthma, Chronic Obstructive Pulmonary Disease (COPD) and Cystic Fibrosis (CF) are
all pulmonary diseases which are characterized by chronic inflammation and an
increase in mucus production. Excess mucus in the airways correlates with
pathophysiology such as a decline in lung function and prolonged bacterial
infections. New drugs to treat these chronic respiratory diseases are currently
being developed and include both inhaled and orally administered compounds.
Whilst oral drugs may be easier to administer, they are more prone to side
effects due to higher bioavailability. Inhaled compounds may show reduced
bioavailability, but face their own unique challenges. For example, thick mucus
in the respiratory tracts of asthma, CF and COPD patients can act as a physical
barrier that impedes drug delivery. Mucus also contains a high number of enzymes
and proteases that may degrade compounds before they reach their site of action.
Furthermore, some classes of drugs are rapidly absorbed across the respiratory
epithelia into systemic circulation, which may limit their duration of action
and/or cause off-target effects. This review discusses some of the different
treatment options that are currently available and the considerations that need
to be taken into account to produce new therapies for the treatment of chronic
respiratory diseases.
PMID- 25126586
TI - IL-6 as a druggable target in psoriasis: focus on pustular variants.
AB - Psoriasis vulgaris (PV) is a cutaneous inflammatory disorder stemming from
abnormal, persistent activation of the interleukin- (IL-)23/Th17 axis. Pustular
psoriasis (PP) is a clinicopathological variant of psoriasis, histopathologically
defined by the predominance of intraepidermal collections of neutrophils.
Although PP pathogenesis is thought to largely follow that of (PV), recent
evidences point to a more central role for IL-1, IL-36, and IL-6 in the
development of PP. We review the role of IL-6 in the pathogenesis of PV and PP,
focusing on its cross-talk with cytokines of the IL-23/Th17 axis. Clinical
inhibitors of IL-6 signaling, including tocilizumab, have shown significant
effectiveness in the treatment of several inflammatory rheumatic diseases,
including rheumatoid arthritis and juvenile idiopathic arthritis; accordingly,
anti-IL-6 agents may potentially represent future promising therapies for the
treatment of PP.
PMID- 25126591
TI - Theranostic Profiling for Actionable Aberrations in Advanced High Risk
Osteosarcoma with Aggressive Biology Reveals High Molecular Diversity: The Human
Fingerprint Hypothesis.
AB - The survival of patients with advanced osteosarcoma is poor with limited
therapeutic options. There is an urgent need for new targeted therapies based on
biomarkers. Recently, theranostic molecular profiling services for cancer
patients by CLIA-certified commercial companies as well as in-house profiling in
academic medical centers have expanded exponentially. We evaluated molecular
profiles of patients with advanced osteosarcoma whose tumor tissue had been
analyzed by one of the following methods: 1. 182-gene next-generation exome
sequencing (Foundation Medicine, Boston, MA), 2. Immunohistochemistry (IHC)/PCR
based panel (CARIS Target Now, Irving, Tx), 3.Comparative genome hybridization
(Oncopath, San Antonio, TX). 4. Single-gene PCR assays, PTEN IHC (MDACC CLIA), 5.
UT Houston morphoproteomics (Houston, TX). The most common actionable aberrations
occur in the PI3K/PTEN/mTOR pathway. No patterns in genomic alterations beyond
the above are readily identifiable, and suggest both high molecular diversity in
osteosarcoma and the need for more analyses to define distinct subgroups of
osteosarcoma defined by genomic alterations. Based on our preliminary
observations we hypothesize that the biology of aggressive and the metastatic
phenotype osteosarcoma at the molecular level is similar to human fingerprints,
in that no two tumors are identical. Further large scale analyses of osteosarcoma
samples are warranted to test this hypothesis.
PMID- 25126592
TI - IDMA-based MAC protocol for satellite networks with consideration on channel
quality.
AB - In order to overcome the shortcomings of existing medium access control (MAC)
protocols based on TDMA or CDMA in satellite networks, interleave division
multiple access (IDMA) technique is introduced into satellite communication
networks. Therefore, a novel wide-band IDMA MAC protocol based on channel quality
is proposed in this paper, consisting of a dynamic power allocation algorithm, a
rate adaptation algorithm, and a call admission control (CAC) scheme. Firstly,
the power allocation algorithm combining the technique of IDMA SINR-evolution and
channel quality prediction is developed to guarantee high power efficiency even
in terrible channel conditions. Secondly, the effective rate adaptation
algorithm, based on accurate channel information per timeslot and by the means of
rate degradation, can be realized. What is more, based on channel quality
prediction, the CAC scheme, combining the new power allocation algorithm, rate
scheduling, and buffering strategies together, is proposed for the emerging IDMA
systems, which can support a variety of traffic types, and offering quality of
service (QoS) requirements corresponding to different priority levels. Simulation
results show that the new wide-band IDMA MAC protocol can make accurate
estimation of available resource considering the effect of multiuser detection
(MUD) and QoS requirements of multimedia traffic, leading to low outage
probability as well as high overall system throughput.
PMID- 25126593
TI - Impacts of groundwater recharge from rubber dams on the hydrogeological
environment in Luoyang Basin, China.
AB - In the rubber dam's impact area, the groundwater total hardness (TH) has declined
since 2000, ultimately dropping to 100-300 mg/L in 2012. pH levels have shown no
obvious changes. NH4-N concentration in the groundwater remained stable from 2000
to 2006, but it increased from 2007 to 2012, with the largest increase up to 0.2
mg/L. NO3-N concentration in the groundwater generally declined in 2000-2006 and
then increased from 2007; the largest increase was to 10 mg/L in 2012. Total
dissolved solids (TDS) of the groundwater showed a general trend of decline from
2000 to 2009, but levels increased after 2010, especially along the south bank of
the Luohe River where the largest increase recorded was approximately 100 mg/L.
This study has shown that the increases in the concentrations of NH4-N and NO3-N
were probably caused by changes in groundwater levels. Nitrates adsorbed by the
silt clay of aeration zone appear to have entered the groundwater through
physical and chemical reactions. TDS increased because of groundwater evaporation
and some soluble ions entered the groundwater in the unsaturated zone. The
distance of the contaminant to the surface of the aquifer became shorter due to
the shallow depth of groundwater, resulting in the observed rise in pollutant
concentrations more pronounced.
PMID- 25126595
TI - Examination of the behavior of gravity quay wall against liquefaction under the
effect of wall width and soil improvement.
AB - Deformation of quay walls is one of the main sources of damage to port facility
while liquefaction of backfill and base soil of the wall are the main reasons for
failures of quay walls. During earthquakes, the most susceptible materials for
liquefaction in seashore regions are loose saturated sand. In this study, effects
of enhancing the wall width and the soil improvement on the behavior of gravity
quay walls are examined in order to obtain the optimum improved region. The FLAC
2D software was used for analyzing and modeling progressed models of soil and
loading under difference conditions. Also, the behavior of liquefiable soil is
simulated by the use of "Finn" constitutive model in the analysis models. The
"Finn" constitutive model is especially created to determine liquefaction
phenomena and excess pore pressure generation.
PMID- 25126594
TI - Cytotoxic constituents from the rhizomes of Curcuma zedoaria.
AB - Curcuma zedoaria also known as Temu putih is traditionally used in food
preparations and treatment of various ailments including cancer. The cytotoxic
activity of hexane, dichloromethane, ethyl acetate, methanol, and the methanol
soxhlet extracts of Curcuma zedoaria rhizomes was tested on two human cancer cell
lines (Ca Ski and MCF-7) and a noncancer cell line (HUVEC) using MTT assay.
Investigation on the chemical components in the hexane and dichloromethane
fractions gave 19 compounds, namely, labda-8(17),12 diene-15,16 dial (1),
dehydrocurdione (2), curcumenone (3), comosone II (4), curcumenol (5),
procurcumenol (6), germacrone (7), zerumbone epoxide (8), zederone (9), 9
isopropylidene-2,6-dimethyl-11-oxatricyclo[6.2.1.0(1,5)]undec-6-en-8-ol (10),
furanodiene (11), germacrone-4,5-epoxide (12), calcaratarin A (13),
isoprocurcumenol (14), germacrone-1,10-epoxide (15), zerumin A (16),
curcumanolide A (17), curcuzedoalide (18), and gweicurculactone (19). Compounds
(1-19) were evaluated for their antiproliferative effect using MTT assay against
four cancer cell lines (Ca Ski, MCF-7, PC-3, and HT-29). Curcumenone (3) and
curcumenol (5) displayed strong antiproliferative activity (IC50 = 8.3 +/- 1.0
and 9.3 +/- 0.3 MUg/mL, resp.) and were found to induce apoptotic cell death on
MCF-7 cells using phase contrast and Hoechst 33342/PI double-staining assay.
Thus, the present study provides basis for the ethnomedical application of
Curcuma zedoaria in the treatment of breast cancer.
PMID- 25126597
TI - The modelled raindrop size distribution of Skudai, Peninsular Malaysia, using
exponential and lognormal distributions.
AB - This paper presents the modelled raindrop size parameters in Skudai region of the
Johor Bahru, western Malaysia. Presently, there is no model to forecast the
characteristics of DSD in Malaysia, and this has an underpinning implication on
wet weather pollution predictions. The climate of Skudai exhibits local
variability in regional scale. This study established five different parametric
expressions describing the rain rate of Skudai; these models are idiosyncratic to
the climate of the region. Sophisticated equipment that converts sound to a
relevant raindrop diameter is often too expensive and its cost sometimes
overrides its attractiveness. In this study, a physical low-cost method was used
to record the DSD of the study area. The Kaplan-Meier method was used to test the
aptness of the data to exponential and lognormal distributions, which were
subsequently used to formulate the parameterisation of the distributions. This
research abrogates the concept of exclusive occurrence of convective storm in
tropical regions and presented a new insight into their concurrence appearance.
PMID- 25126596
TI - Sequence variation in Toxoplasma gondii rop17 gene among strains from different
hosts and geographical locations.
AB - Genetic diversity of T. gondii is a concern of many studies, due to the
biological and epidemiological diversity of this parasite. The present study
examined sequence variation in rhoptry protein 17 (ROP17) gene among T. gondii
isolates from different hosts and geographical regions. The rop17 gene was
amplified and sequenced from 10 T. gondii strains, and phylogenetic relationship
among these T. gondii strains was reconstructed using maximum parsimony (MP),
neighbor-joining (NJ), and maximum likelihood (ML) analyses. The partial rop17
gene sequences were 1375 bp in length and A+T contents varied from 49.45% to
50.11% among all examined T. gondii strains. Sequence analysis identified 33
variable nucleotide positions (2.1%), 16 of which were identified as transitions.
Phylogeny reconstruction based on rop17 gene data revealed two major clusters
which could readily distinguish Type I and Type II strains. Analyses of sequence
variations in nucleotides and amino acids among these strains revealed high ratio
of nonsynonymous to synonymous polymorphisms (>1), indicating that rop17 shows
signs of positive selection. This study demonstrated the existence of slightly
high sequence variability in the rop17 gene sequences among T. gondii strains
from different hosts and geographical regions, suggesting that rop17 gene may
represent a new genetic marker for population genetic studies of T. gondii
isolates.
PMID- 25126599
TI - Influence of vacancy defect on surface feature and adsorption of Cs on GaN(0001)
surface.
AB - The effects of Ga and N vacancy defect on the change in surface feature, work
function, and characteristic of Cs adsorption on a (2 * 2) GaN(0001) surface have
been investigated using density functional theory with a plane-wave ultrasoft
pseudopotential method based on first-principles calculations. The covalent bonds
gain strength for Ga vacancy defect, whereas they grow weak for N vacancy defect.
The lower work function is achieved for Ga and N vacancy defect surfaces than
intact surface. The most stable position of Cs adatom on Ga vacancy defect
surface is at T1 site, whereas it is at B(Ga) site on N vacancy defect surface.
The E(ads) of Cs on GaN(0001) vacancy defect surface increases compared with that
of intact surface; this illustrates that the adsorption of Cs on intact surface
is more stable.
PMID- 25126598
TI - The influence of obesity on different genders in patients with obstructive sleep
apnea.
AB - Obesity is considered to be a major contributing factor to obstructive sleep
apnea (OSA); however, there is limited evidence with regard to gender
predominance. We analyzed 2345 patients (339 females) in correlation with body
mass index (BMI) and OSA severity. Male AHIs were significantly higher than
female AHIs in each BMI group. As the BMI increased, the AHI increased in both
males and females, and this trend was more obvious in males. For BMI-matched male
and female patients with OSA, the severity of OSA was higher in males. As BMI
increased, the severity of OSA increased more obviously in males. Our findings
suggest that increased body fat contributes to the pathogenesis of OSA more in
males than in females and that obesity plays a more significant role in
contributing to OSA in male patients.
PMID- 25126601
TI - Characterization of coal porosity for naturally tectonically stressed coals in
Huaibei coal field, China.
AB - The enrichment of coalbed methane (CBM) and the outburst of gas in a coal mine
are closely related to the nanopore structure of coal. The evolutionary
characteristics of 12 coal nanopore structures under different natural
deformational mechanisms (brittle and ductile deformation) are studied using a
scanning electron microscope (SEM) and low-temperature nitrogen adsorption. The
results indicate that there are mainly submicropores (2~5 nm) and supermicropores
(<2 nm) in ductile deformed coal and mesopores (10~100 nm) and micropores (5~10
nm) in brittle deformed coal. The cumulative pore volume (V) and surface area (S)
in brittle deformed coal are smaller than those in ductile deformed coal which
indicates more adsorption space for gas. The coal with the smaller pores exhibits
a large surface area, and coal with the larger pores exhibits a large volume for
a given pore volume. We also found that the relationship between S and V turns
from a positive correlation to a negative correlation when S > 4 m(2)/g, with
pore sizes <5 nm in ductile deformed coal. The nanopore structure (<100 nm) and
its distribution could be affected by macromolecular structure in two ways.
Interconversion will occur among the different size nanopores especially in
ductile deformed coal.
PMID- 25126602
TI - Large-area binary blazed grating coupler between nanophotonic waveguide and LED.
AB - A large-area binary blazed grating coupler for the arrayed waveguide grating
(AWG) demodulation integrated microsystem on silicon-on-insulator (SOI) was
designed for the first time. Through the coupler, light can be coupled into the
SOI waveguide from the InP-based C-band LED for the AWG demodulation integrated
microsystem to function. Both the length and width of the grating coupler are 360
MUm, as large as the InP-based C-band LED light emitting area in the system. The
coupler was designed and optimized based on the finite difference time domain
method. When the incident angle of the light source is 0 degrees , the coupling
efficiency of the binary blazed grating is 40.92%, and the 3 dB bandwidth is 72
nm at a wavelength of 1550 nm.
PMID- 25126603
TI - A novel modulation classification approach using Gabor filter network.
AB - A Gabor filter network based approach is used for feature extraction and
classification of digital modulated signals by adaptively tuning the parameters
of Gabor filter network. Modulation classification of digitally modulated signals
is done under the influence of additive white Gaussian noise (AWGN). The
modulations considered for the classification purpose are PSK 2 to 64, FSK 2 to
64, and QAM 4 to 64. The Gabor filter network uses the network structure of two
layers; the first layer which is input layer constitutes the adaptive feature
extraction part and the second layer constitutes the signal classification part.
The Gabor atom parameters are tuned using Delta rule and updating of weights of
Gabor filter using least mean square (LMS) algorithm. The simulation results show
that proposed novel modulation classification algorithm has high classification
accuracy at low signal to noise ratio (SNR) on AWGN channel.
PMID- 25126604
TI - The potential of using brain images for authentication.
AB - Biometric recognition (also known as biometrics) refers to the automated
recognition of individuals based on their biological or behavioral traits.
Examples of biometric traits include fingerprint, palmprint, iris, and face. The
brain is the most important and complex organ in the human body. Can it be used
as a biometric trait? In this study, we analyze the uniqueness of the brain and
try to use the brain for identity authentication. The proposed brain-based
verification system operates in two stages: gray matter extraction and gray
matter matching. A modified brain segmentation algorithm is implemented for
extracting gray matter from an input brain image. Then, an alignment-based
matching algorithm is developed for brain matching. Experimental results on two
data sets show that the proposed brain recognition system meets the high accuracy
requirement of identity authentication. Though currently the acquisition of the
brain is still time consuming and expensive, brain images are highly unique and
have the potential possibility for authentication in view of pattern recognition.
PMID- 25126605
TI - An analysis dictionary learning algorithm under a noisy data model with
orthogonality constraint.
AB - Two common problems are often encountered in analysis dictionary learning (ADL)
algorithms. The first one is that the original clean signals for learning the
dictionary are assumed to be known, which otherwise need to be estimated from
noisy measurements. This, however, renders a computationally slow optimization
process and potentially unreliable estimation (if the noise level is high), as
represented by the Analysis K-SVD (AK-SVD) algorithm. The other problem is the
trivial solution to the dictionary, for example, the null dictionary matrix that
may be given by a dictionary learning algorithm, as discussed in the learning
overcomplete sparsifying transform (LOST) algorithm. Here we propose a novel
optimization model and an iterative algorithm to learn the analysis dictionary,
where we directly employ the observed data to compute the approximate analysis
sparse representation of the original signals (leading to a fast optimization
procedure) and enforce an orthogonality constraint on the optimization criterion
to avoid the trivial solutions. Experiments demonstrate the competitive
performance of the proposed algorithm as compared with three baselines, namely,
the AK-SVD, LOST, and NAAOLA algorithms.
PMID- 25126606
TI - Dynamic response and optimal design of curved metallic sandwich panels under
blast loading.
AB - It is important to understand the effect of curvature on the blast response of
curved structures so as to seek the optimal configurations of such structures
with improved blast resistance. In this study, the dynamic response and
protective performance of a type of curved metallic sandwich panel subjected to
air blast loading were examined using LS-DYNA. The numerical methods were
validated using experimental data in the literature. The curved panel consisted
of an aluminum alloy outer face and a rolled homogeneous armour (RHA) steel inner
face in addition to a closed-cell aluminum foam core. The results showed that the
configuration of a "soft" outer face and a "hard" inner face worked well for the
curved sandwich panel against air blast loading in terms of maximum deflection
(MaxD) and energy absorption. The panel curvature was found to have a monotonic
effect on the specific energy absorption (SEA) and a nonmonotonic effect on the
MaxD of the panel. Based on artificial neural network (ANN) metamodels,
multiobjective optimization designs of the panel were carried out. The
optimization results revealed the trade-off relationships between the blast
resistant and the lightweight objectives and showed the great use of Pareto front
in such design circumstances.
PMID- 25126607
TI - Graphs and matroids weighted in a bounded incline algebra.
AB - Firstly, for a graph weighted in a bounded incline algebra (or called a dioid), a
longest path problem (LPP, for short) is presented, which can be considered the
uniform approach to the famous shortest path problem, the widest path problem,
and the most reliable path problem. The solutions for LPP and related algorithms
are given. Secondly, for a matroid weighted in a linear matroid, the maximum
independent set problem is studied.
PMID- 25126608
TI - A new kind of fuzzy n-ary hypergroups in the framework of soft set theory.
AB - Maji et al. introduced the concept of fuzzy soft sets as a generalization of the
standard soft sets and presented an application of fuzzy soft sets in a decision
making problem. The aim of this paper is to apply the concept of fuzzy soft sets
to n-ary hypergroup theory. The concepts of (?(gamma), ?(gamma) ? q(delta))-fuzzy
soft (invertible) n-ary subhypergroups over a commutative n-ary hypergroup are
introduced and some related properties and characterizations are obtained. The
homomorphism properties of (?(gamma), ?(gamma) ? q(delta))-fuzzy soft
(invertible) n-ary subhypergroups are also derived.
PMID- 25126609
TI - Obtaining P3P privacy policies for composite services.
AB - With the development of web services technology, web services have changed from
single to composite services. Privacy protection in composite services is
becoming an important issue. P3P (platform for privacy preferences) is a privacy
policy language which was designed for single web services. It enables service
providers to express how they will deal with the privacy information of service
consumers. In order to solve the problem that P3P cannot be applied to composite
services directly, we propose a method to obtain P3P privacy policies for
composite services. In this method, we present the definitions of Purpose,
Recipient, and Retention elements as well as Optional and Required attributes for
P3P policies of composite services. We also provide an instantiation to
illustrate the feasibility of the method.
PMID- 25126610
TI - Mycotoxins and mycotoxigenic fungi in poultry feed for food-producing animals.
AB - Moulds are capable of reducing the nutritional value of feedstuff as well as
elaborating several mycotoxins. Mycotoxin-contaminated feed has adverse effects
on animal health and productivity. Also, mycotoxins may be carried over into meat
and eggs when poultry are fed with contaminated feed. In a point prevalence study
feedstuff used for poultry nutrition in Argentina was analyzed for fungal flora,
natural incidence of selected mycotoxins, and nutritional quality. Ten mould
genera were recovered, six of them known to be mycotoxigenic. More than 28
species were determined. Fumonisins were detected in all the samples (median
1,750 ppb). Forty-four out of 49 samples (90%) were contaminated with DON (median
222 ppb) and OTA (median 5 ppb). Also, 44 out of 49 samples were contaminated
with aflatoxins (median 2.685 ppb), 42 samples (86%) with ZEA (median 50 ppb),
and 38 samples (78%) with T2-toxin (median 50 ppb). Ninety percent of the samples
had at least one type of nutritional deficiency. This study indicates the need
for continuous assessment of the mycological status of animal feed production, in
order to feed animals for optimal performance ensuring food safety.
PMID- 25126611
TI - Natural recovery and planned intervention in coastal wetlands: Venice Lagoon
(northern Adriatic Sea, Italy) as a case study.
AB - The goals of conservation and sustainable use of environmental ecosystems have
increased the need for detailed knowledge of ecological evolution and responses
to both anthropogenic pressures and recovery measures. The present study shows
the effects of natural processes and planned intervention in terms of reducing
nutrient inputs in a highly exploited coastal lagoon, describing its evolution
over a 16-year period from the late 1980s (when eutrophication was at its peak)
until 2003. Changes in nutrient and carbon concentrations in the top layer of
sediments were investigated in parallel with macroalgal and seagrass biomass in
the most anthropized basin of Venice Lagoon in four surveys conducted in
accordance with the same protocols in 1987, 1993, 1998, and 2003. A pronounced
reduction in trophic state (mainly total nitrogen, organic phosphorus, and
organic carbon concentrations) and macroalgal biomass was recorded, together with
the progressive expansion of seagrass meadows. General considerations are also
made on the effects of Manila clam farming and the shift from illegal to managed
clam farming.
PMID- 25126613
TI - Cerebellar Ataxia and CoQ10 Deficiency.
PMID- 25126614
TI - Toward the future.
PMID- 25126612
TI - Voltage dependent anion channel is redistributed during Japanese encephalitis
virus infection of insect cells.
AB - Despite the availability of an effective vaccine, Japanese encephalitis remains a
significant cause of morbidity and mortality in many parts of Asia. Japanese
encephalitis is caused by the Japanese encephalitis virus (JEV), a mosquito
transmitted flavivirus. Many of the details of the virus replication cycle in
mosquito cells remain unknown. This study sought to determine whether GRP78, a
well-characterized flavivirus E protein interacting protein, interacted with JEV
E protein in insect cells, and whether this interaction was mediated at the cell
surface. GRP78 was shown to interact with JEV E protein by coimmunoprecipitation,
and was additionally shown to interact with voltage dependent anion protein
(VDAC) through the same methodology. Antibody inhibition experiments showed that
neither GRP78 nor VDAC played a role in JEV internalization to insect cells.
Interestingly, VDAC was shown to be significantly relocalized in response to JEV
infection, and significant levels of colocalization between VDAC and GRP78 and
VDAC and ribosomal L28 protein were seen in JEV infected but not uninfected
cells. This is the first report of relocalization of VDAC in response to JEV
infection and suggests that this may be a part of the JEV replication strategy in
insect cells.
PMID- 25126615
TI - Bio-Emulation: biomimetically emulating nature utilizing a histoanatomic
approach; visual synthesis.
AB - A thorough understanding of the spatial distribution pertaining to the histo
anatomic coronal structures and dynamic light interaction of the natural
dentition provides the dental team with the ultimate strategic advantage with
regards to optical integration of the final restoration. The second part of this
two-part article will attempt to provide insight on the illumination
interactivity and the spatial arrangement of the coronal elements of natural
teeth through the utilization of this knowledge in the clinical and technical
restorative approach. The main goals for this article are to cognize histo
anatomic visualization by introducing: (1) Dynamic light interaction, (2) the 9
elements of visual synthesis, (3) dynamic infinite optical thickness, and (4)
amplified visual perception effect of the hard dental tissues. Furthermore, a
diversification of photographic illumination techniques will be illustrated in
order to juxtapose optical associations between the enamel/dentinoenamel
complex/dentin nexus.
PMID- 25126616
TI - Ceramic adhesive restorations and biomimetic dentistry: tissue preservation and
adhesion.
AB - Thanks to sophisticated adhesive techniques in contemporary dentistry, and the
development of composite and ceramic materials, it is possible to reproduce a
biomimetic match between substitution materials and natural teeth substrates.
Biomimetics or bio-emulation allows for the association of two fundamental
parameters at the heart of current therapeutic treatments: tissue preservation
and adhesion. This contemporary concept makes the retention of the integrity of
the maximum amount of dental tissue possible, while offering exceptional clinical
longevity, and maximum esthetic results. It permits the conservation of the
biological, esthetic, biomechanical and functional properties of enamel and
dentin. Today, it is clearly possible to develop preparations allowing for the
conservation of the enamel and dentin in order to bond partial restorations in
the anterior and posterior sectors therefore limiting, as Professor Urs Belser
from Geneva indicates, "the replacement of previous deficient crowns and
devitalized teeth whose conservation are justified but whose residual structural
state are insufficient for reliable bonding."1 This article not only addresses
ceramic adhesive restoration in the anterior area, the ambassadors of biomimetic
dentistry, but also highlights the possibility of occasionally integrating one or
two restorations at the heart of the smile as a complement to extensive
rehabilitations that require more invasive treatment.
PMID- 25126618
TI - Influence of enamel composite thickness on value, chroma and translucency of a
high and a nonhigh refractive index resin composite.
AB - OBJECTIVES: To evaluate the influence of thickness on the optical properties of
two enamel shade composites, one with a high refractive index and one
traditional. METHODS: A medium value enamel shade was selected from the resin
composites Enamel Plus HRi (UE2) and Enamel Plus HFO (GE2). Enamel Plus HRi is a
high refractive index composite. Samples were fabricated in five different
thicknesses: 0.3, 0.5, 1, 1.5 and 2 mm. Three specimens per material and
thickness were fabricated. Three measurements per sample, over white, black and
dentin composite background were generated with a spectrophotometer (Spectroshade
Micro, MHT). Value, chroma, translucency and color differences (DeltaE) of the
specimens were calculated. RESULTS were analyzed by the Pearson correlation test,
ANOVA and a post-hoc Tukey test. RESULTS: Increasing the thickness of the enamel
layers decreased the translucency and the chroma of the substrate for both
materials tested. For HRi the increase of the thickness resulted in an increase
of the value, whereas for HFO it resulted in a reduction of the value. The two
composites showed a significant difference in value for each thickness, but not
in translucency and chroma. Color difference between them was perceptible in
layers equal or higher than 0.5 mm. CONCLUSIONS: The high refractive index enamel
(HRi) composite exhibits different optical behavior compared to the traditional
one (HFO). HRi enamel composite behaves more like natural enamel as by increasing
the thickness of the enamel layer, the value also increases.
PMID- 25126617
TI - Anthropometric analysis of anterior maxillary teeth with digital photography - a
study in a Portuguese sample.
AB - SUMMARY: Establishing a geometrical pattern of the anterior maxillary sector has
been attempted for a long time. The Golden Proportion, Preston's Percentage,
Golden Percentage, Recurring Esthetic Dental (RED) Proportion and, most recently,
Gauge Proportion, are theories that try to apply mathematical and geometrical
relations to the anterior maxillary teeth. PURPOSE: To study the anterior
maxillary teeth proportions of a Portuguese population sample and see if any of
the existent anthropometric proportions can be applied to the oral rehabilitation
of this population. MATERIALS AND METHODS: Standardized frontal and lateral
images of 50 dental patient smiles included in the inclusion criteria were
captured. The widths and heights of maxillary anterior teeth were measured using
image-processing software and data were statistically analyzed using a parametric
test (t test). RESULTS: The widths and heights were concordant with the values
described by the Gauge Proportion. However, they were above the recommended value
of 78% for the width/height proportion advocated. The proportions between the
widths of the maxillary anterior teeth were not constant as proposed by the
Golden Proportion and the RED Proportion. The Preston Proportion was found to be
in concordance with the studied population. The values observed were closer to
the Golden Percentage. Considering genre, there was a statistically significant
difference. Male patients had teeth with larger dimensions than females.
CONCLUSION: Within the limitations of this study, mainly concerned to the sample
size, it may be concluded that the widths and heights of the anterior maxillary
teeth were coincident with the Gauge Proportion. Both the Golden Proportion and
the RED proportion are unsuitable methods to relate the widths of the maxillary
anterior teeth unlike the Preston's Proportion. The Golden Percentage was close
to the percentages observed and could be adjusted to be taken in consideration to
this population.
PMID- 25126619
TI - Treatment planning and dental rehabilitation of a periodontally compromised
partially edentulous patient: a case report - Part I.
AB - When planning a prosthetic rehabilitation of a periodontally compromised case,
the clinician is often confronted with difficulties and dilemmas related to
selecting the appropriate treatment modality that would provide a long-term
longevity in terms of function and esthetics. In such cases, a correct diagnosis
and prognosis of the intraoral situation supported by evidence-based dentistry is
the basis for the establishment of a proper treatment strategy. In this two-part
treatment planning series, a systematic approach of patient examination and
prognosis of each tooth is presented. Furthermore, different removable and fixed
treatment possibilities are described and the rationale governing the decision
making process is revealed. The execution of the final treatment plan as
specified by the concept of comprehensive dental care is outlined and the final
outcome is discussed according to the literature.
PMID- 25126620
TI - The effects of forehead and neck position on esthetics of class I, II and III
profiles.
AB - INTRODUCTION: All parts of the face, other than jaw relationships, should be
considered in orthodontic treatment planning. The role of forehead and neck in
facial esthetics is well known; however, the majority of conventional facial
analysis methods have not considered them. Neck and forehead may confer mutual
effects on equilibrium and on esthetics of other facial components, and may
change the overall convexity/concavity view of the profile. Therefore, the aim of
this study was to assess the effect of anteroposterior position of the forehead
and neck on the esthetics of skeletal class I, II and III jaw relationships using
profile silhouettes. METHODS: Class II and III jaw relationships were constructed
on the silhouette of a class I normal profile by altering the mandibular
position. Retruded, normal and protruded positions were also applied for the
forehead and neck. Three hundred Iranian laypeople (150 men, 150 women) scored
the esthetics of profile silhouettes from 1 to 7. Half of the participants were
told to consider the profiles as a man, and the other half were told to consider
them as a woman. Data were analyzed using non-parametric methods. RESULTS: Class
I jaw relation was found to be the most beautiful profile followed by class II
and III respectively. Esthetics of different positions of the neck and forehead
were significantly different (P < 0.05). In subjects with a normal neck and
forehead position, and those with a retruded neck, the best esthetic relationship
was class I, and the worst was class III. For protruded foreheads, the best jaw
relationship was class II for females and class I for males, and the worst was
class III for both. In a retruded forehead position, the most preferred jaw
relationship was class I, and the worst was class II. For profiles with a
protruded neck, the best esthetics was found to be in class III jaw relationship,
and the worst was in class II. There was a small difference in scoring for male
and female profiles (P < 0.05); there were also small differences in scoring
trends of men and women (P < 0.05). CONCLUSION: This study showed that the
anteroposterior position of the forehead and neck affects the esthetics of jaw
relationships in profile view. In laypeople's opinions, in a normal profile, the
overall appearance is more important compared to the independent position of the
neck and forehead; however, having jaw abnormalities, the neck plays an important
independent role. The preferred jaw relation for profiles with each forehead or
neck position was introduced.
PMID- 25126621
TI - Comparison of marginal fit of Lava CAD/CAM crown-copings with two finish lines.
AB - PURPOSE: Marginal fit is valued as one of the most important criteria for the
clinical quality and success of all-ceramic crowns. The aim of this in vitro
study was to investigate the marginal fit of Lava Zirconia crown-copings on
chamfer and shoulder preparations. METHODS: Two acrylic model teeth were selected
to simulate the clinical preparations: one molar was prepared with a chamfer
finish line (C) and one premolar was prepared with a rounded shoulder finish line
(RS). Each resin model was duplicated 10 times using silicon-based impression
material and poured in type IV dental stone for the fabrication of working dies.
A total of 20 copings were divided into two groups (n = 10 for each finish line).
Fifty measuring locations were chosen randomly along the margin on the dies and
the gap width - vertical marginal discrepancy - was measured under a light
microscope with a magnification of x100. Measurements were made without
cementation. The mean marginal gap widths and standard deviations were calculated
and a one-way analysis of variance (ANOVA) was performed for different types of
preparations in order to detect differences (alpha = 0.05). RESULTS: The mean
marginal gap was 30 +/- 3 MUm for the C group and 28 +/- 4 MUm for the RS group.
The one-way ANOVA showed no statistical significant difference between the two
groups (P = 0.23). CONCLUSIONS: Within the limitations of this study, the
marginal discrepancies were all within the clinical acceptable standard set at
120 MUm. Chamfer and shoulder preparations did not show differences regarding the
gap dimension. CLINICAL SIGNIFICANCE: Bur design is an easily selected parameter
before natural tooth preparation. Both tested finish lines are able to help
clinicians in obtaining acceptable marginal fit values for the investigated
zirconia copings.
PMID- 25126622
TI - The timing and operational management of the variables of bleaching in cases of
rehabilitation in the esthetic field.
AB - Managing esthetic restoration in the presence of discolored teeth is a challenge
for both the clinical team and clinician, whose aim is to use methods that are as
minimally invasive as possible, and materials that allow the preservation of
dental tissue. Should one wish to act on the discoloration of teeth that are to
be restored, or on adjacent ones, it becomes essential to take action on dental
tissues. This is done through bleaching and dental restoration, using materials
that allow various clinical situations to be managed, such as those with
different tonalities between the teeth: prosthetic materials that offer adequate
uniformity in their results in those areas where it is necessary to mask the
discoloration. The use of technology such as bleaching, and ceramic materials
simultaneously can achieve excellent cosmetic results. This article explains how
to integrate bleaching compared to prosthetic treatment, in terms of time, in the
various cases of discoloration, and what factors to consider when choosing the
timing.
PMID- 25126623
TI - Effect of Er,Cr:YSGG laser treatment on microshear bond strength of zirconia to
resin cement before and after sintering.
AB - PURPOSE: To evaluate the effect of Er,Cr:YSGG laser treatment on microshear bond
strength of zirconia to resin cement before and after sintering. MATERIALS AND
METHODS: Ninety pre-sintered yttrium-stabilized tetragonal zirconia specimens (4
* 3 * 2 mm) were divided into 6 groups (n = 15). In group C, sintered zirconia
was not treated (control group). In groups AS2 and AS3, sintered zirconia blocks
were irradiated by Er,Cr:YSGG using a power of 2 and 3 W, respectively. Groups
PS2 and PS3 consisted of pre-sintered blocks conditioned by Er,Cr:YSGG at 2 and 3
W, respectively. In group AA, sintered zirconia was air abraded with 50-MUm
alumina powder. One block was made using the same preparations as mentioned above
and was morphologically assessed by SEM. Microcylinders of Panavia F 2.0 were
placed on the treated surface of the groups. Samples were incubated at 37 degrees
C and 98% humidity for 48 h and then subjected to microshear bond strength
testing. The mode of failure was evaluated. Data were analyzed by one-way ANOVA
and Tukey's HSD test (p < 0.05). RESULTS: There was a statistically significant
difference between group AA and the others (p < 0.0001). A significant difference
was also noted between groups AS3 and C (p = 0.031). Complete surface roughness
was seen in group AA and the bond failure was mostly cohesive, while in laser
treated groups, the surfaces roughness was much lower vs other groups, and the
mode of failure was mostly adhesive. CONCLUSION: Laser treatment of pre-sintered
Y-TZP cannot be recommended for improving the bond. Although sandblasting of
sintered Y-TZP yielded better results than the rest of the groups, 3 W power
after sintering can also be effective in enhancing the bonding strength of resin
cement to zirconia.
PMID- 25126630
TI - Stage-two surgery using collagen soft tissue grafts: clinical cases and
ultrastructural analysis.
AB - OBJECTIVE: To present the application of two different soft tissue grafts around
dental implants during stage-two surgery. Furthermore, the ultrastructure of
these materials is shown and discussed using scanning electron microscopy (SEM).
SUMMARY: Although soft tissue autografts may be currently regarded as the gold
standard, harvesting of these grafts might lead to higher morbidity, longer chair
time, and intra-/postoperative complications at the donor site. New developments
in collagen scaff olds have provided an alternative to successfully replace
autologous grafts in clinical practice. The SEM pictures clearly show the
different composition of a bilayer scaff old (collagen matrix, CM) and a porcine
acellular dermal matrix (ADM). These distinctive properties lead to different
possible indications. Within the presented cases, ADM was used to augment the
ridge contour and was placed into a buccal pouch to achieve complete coverage and
an uneventful closed healing. On the other side, CM was left exposed to the oral
cavity to successfully gain keratinized mucosa around and between two dental
implants.
PMID- 25126631
TI - Dental prosthetist experience with oral mucosal screening and referral.
AB - OBJECTIVES: This study aimed to investigate dental prosthetists' experiences with
screening and referral for suspicious oral mucosal pathology. METHOD AND
MATERIALS: Questionnaires regarding oral mucosal screening and referral were
mailed to 300 randomly selected dental prosthetists in Australia for
selfcompletion. Non-responders were sent replacement questionnaires up to three
times, according to the Dillman method. RESULTS: A total of 179 prosthetists
returned completed questionnaires resulting in a response rate of 64.9% after
excluding 24 due to incorrectly listed addresses. Most participants reported that
they checked all new patients for oral mucosal pathology (99.4%) and most
reported that they checked all recall patients for mucosal pathology (86%). Most
participants had detected a suspicious lesion (86%) and most had referred for a
suspicious lesion (77.3%). CONCLUSION: Australian dental prosthetists appear
motivated to perform oral mucosal screening and will refer suspicious oral
mucosal pathology when detected.
PMID- 25126632
TI - A pilot study on spatial changes in the maxilla caused by osteopathic therapy.
AB - OBJECTIVES: A variety of theories on the pathogenesis of temporomandibular
disorders (TMD) exists resulting in treatment approaches ranging from the
fabrication of occlusal splints to alternative treatment modalities such as
osteopathy. The goal of this pilot study was to investigate whether osteopathic
treatment causes spatial changes in the maxilla. METHOD AND MATERIALS: Following
ethics commission approval and informed patient consent, three patients diagnosed
with TMD participated in this investigation. In addition to regular treatment, an
individualized mandibular occlusal splint was fabricated and a maxillary silicone
impression was made. Following osteopathic treatment, the splint was adapted
intraorally and another maxillary impression was made. Before and after
treatment, the splint and the impressions were scanned three-dimensionally. The
resulting images were superimposed using best-fit matching algorithms. RESULTS:
Inconsistent spatial changes in the posterior areas were observed both in the
maxillary impressions as well as in the mandibular splints reaching maximum
absolute values of 0.50 mm. CONCLUSION: Based on this pilot study, it appears
that osteopathic treatment may be capable of inducing spatial changes in the
maxilla due to sutural movement thereby validating the fundamental principles of
osteopathic treatment. Although, based on the study conducted, it cannot be
concluded that osteopathy constitutes a successful treatment alternative in TMD
patients, practitioners should be aware of this treatment modality.
PMID- 25126633
TI - An idiosyncratic post-traumatic tetrad: compound odontome, dentigerous cyst,
impaction, and double-dilaceration.
AB - OBJECTIVE: This report describes the case of a 13-year-old patient who
experienced traumatic intrusion of the primary maxillary right central incisor
and subsequently suffered an atypical tetrad, comprising of an unerupted compound
odontoma associated with a dentigerous cyst, and an impacted, doubly dilacerated
permanent maxillary right central incisor; however, the high interconnectivity of
the occurrence of four pathologies together is unusual has not previously been
reported. SUMMARY: The pathologies were detected 7 years after trauma; surgical
removal of odontome along with the dentigerous cyst was performed, followed by
orthodontic extrusion of the impacted double-dilacerated permanent central
incisor. The 18-month follow-up shows no pathology, no gingival recession, and
normal probing depth.
PMID- 25126634
TI - Conservative restorations combined with gingival zenith contour technique.
AB - The symmetry, shape, contour, and size of teeth play an important role in the
esthetics of the anterior maxillary region of the mouth. However, abnormalities
in symmetry and contour can considerably influence the esthetic parameters.
Consequently, rehabilitation performed in this region can be challenging and,
frequently, multidisciplinary treatment planning that includes esthetics,
function, structure, and biologic aspects is paramount. The high demand for
esthetic rehabilitations has, therefore, allowed the effective use of minimally
invasive techniques to obtain results that mimic natural teeth. This article
presents a case report in which both esthetic and functional rehabilitation were
obtained by recontouring the gingival zenith followed by placing
ultraconservative porcelain veneers.
PMID- 25126635
TI - Prosthetic rehabilitation of congenitally missing canines: a case series.
AB - Hypodontia is a relatively common finding, although rarely are the canines the
missing teeth. Congenitally missing canines are challenging to treat because of
their unique role in the masticatory system and the fact that they are in the
esthetic zone. This article discusses two patients with missing permanent
canines, various treatment planning considerations, and the provided prosthetic
solutions.
PMID- 25126636
TI - Marginal and internal fit of curved anterior CAD/CAM-milled zirconia fixed dental
prostheses: an in-vitro study.
AB - OBJECTIVE: To test whether or not different types of CAD/CAM systems, processing
zirconia in the densely and in the pre-sintered stage, lead to differences in the
accuracy of 4-unit anterior fixed dental prosthesis (FDP) frameworks, and to
evaluate the efficiency. METHOD AND MATERIALS: 40 curved anterior 4-unit FDP
frameworks were manufactured with four different CAD/CAM systems: DCS Precident
(DCS) (control group), Cercon (DeguDent) (test group 1), Cerec InLab (Sirona)
(test group 2), Kavo Everest (Kavo) (test group 3). The DCS System was chosen as
the control group because the zirconia frameworks are processed in its densely
sintered stage and there is no shrinkage of the zirconia during the manufacturing
process. The initial fit of the frameworks was checked and adjusted to a
subjectively similar level of accuracy by one dental technician, and the time
taken for this was recorded. After cementation, the frameworks were embedded into
resin and the abutment teeth were cut in mesiodistal and orobuccal directions in
four specimens. The thickness of the cement gap was measured at 50* (internal
adaptation) and 200* (marginal adaptation) magnification. The measurement of the
accuracy was performed at four sites. Site 1: marginal adaptation, the marginal
opening at the point of closest perpendicular approximation between the die and
framework margin. Site 2: Internal adaptation at the chamfer. Site 3: Internal
adaptation at the axial wall. Site 4: Internal adaptation in the occlusal area.
The data were analyzed descriptively using the ANOVA and Bonferroni/ Dunn tests.
RESULTS: The mean marginal adaptation (site 1) of the control group was 107 +/-
26 MUm; test group 1, 140 +/- 26 MUm; test group 2, 104 +/- 40 MUm; and test
group 3, 95 +/- 31 MUm. Test group 1 showed a tendency to exhibit larger marginal
gaps than the other groups, however, this difference was only significant when
test groups 1 and 3 were compared (P = .0022; Bonferroni/Dunn test).
Significantly more time was needed for the adjustment of the frameworks of test
group 1 compared to the other test groups and the control group (21.1 min vs 3.8
min) (P < .0001; Bonferroni/Dunn test). For the adjustment of the frameworks of
test groups 2 and 3, the same time was needed as for the frameworks of the
control group. CONCLUSIONS: No differences of the framework accuracy resulting
from the different CAM and CAD/CAM procedures were found; however, only after
adjustment of the fit by an experienced dental technician. Hence, the influence
of a manual correction of the fit was crucial, and the efforts differed for the
tested systems. The CAM system led to lower initial accuracy of the frameworks
than the CAD/CAM systems, which may be crucial for the dental laboratory. The
stage of the zirconia materials used for the different CAD/CAM procedures, ie
presintered or densely sintered, exhibited no influence.
PMID- 25126637
TI - Prevalence of peri-implantitis in patients with implant-supported fixed
prostheses.
AB - OBJECTIVE: The purpose of this study was to evaluate periimplantitis prevalence
in patients using implant-supported fixed prostheses that did not have any
routine maintenance care. METHOD AND MATERIALS: A total of 161 implants (27
patients) were evaluated in patients using implant-supported fixed prostheses.
Collected data included information related to patient general health and local
factors such as characteristics of implants, time in function, type of loading,
positioning, Modified Bleeding Index, bacterial plaque, bleeding on probing
(BOP), marginal recession, probing depth (PD), keratinized mucosa, and
radiographic bone loss (BL). Factors related to the prostheses were also
evaluated. The exclusion criteria were patients that have had any follow-up visit
for plaque control of the prosthesis and/or the implants. RESULTS: From a total
of 161 implants, 116 (72%) presented without peri-implantitis (PD > 4 mm + BOP +
BL > 2 mm) while 45 (28%) had some sign of the disease. Implants placed in the
maxilla were 2.98 times more likely to develop the disease (P < .05). Moreover,
patients aged <= 60 years old were 3.24 times more likely to develop peri
implantitis (P < .05). Another analysis with statistical relevance (P < .05) was
that implants with less than 3 mm interimplant distance were three times more
likely to have peri-implantitis. There was no statistical relevance considering
other analyses. CONCLUSION: It can be concluded that patients aged <= 60 years
have a greater chance of presenting periimplantitis, as well as for implants
positioned in the maxilla and those placed with an interimplant distance < 3 mm.
PMID- 25126639
TI - Publishing negative results--sometimes it is more important!
PMID- 25126638
TI - The sealing ability of ProRoot MTA when placed as an apical barrier using three
different techniques: an in-vitro apexification model.
AB - OBJECTIVE: To assess the sealing ability of ProRoot MTA when placed as an apical
barrier using three different techniques. METHOD AND MATERIALS: Sixty freshly
extracted single-rooted human teeth were decoronated and standardized to a root
length of 15 mm. The root segments were prepared with Gates Glidden burs to
simulate a divergent open apex of immature teeth and randomly assigned into three
experimental groups of 20 samples each. MTA (5 mm) was placed by pluggers (Group
A), paper points (Group B), or ultrasonic tips (Group C). A cotton pellet
moistened with saline was placed in the root canals till the material set, and
the coronal portion was sealed with Cavit. After 24 hours, the Cavit and cotton
pellet were removed and the canals dried and obturated with warm guttapercha
(Obtura) and AH 26 sealer. Coronal portions of all samples were then sealed with
Cavit. All root segments were double-coated with nail varnish except for the open
apex and were exposed to methylene blue dye for 48 hours at room temperature. The
samples were sectioned longitudinally (layer thickness 0.4 mm) and the extent of
dye penetration was measured with a stereomicroscope (magnification 20*).
RESULTS: The mean depth (+/- standard deviation) of dye leakage for Group A was
1.34 +/- 0.5 mm, Group B 1.25 +/- 0.4 mm, and Group C 1.14 +/- 0.4 mm. There were
no significant differences among the three experimental groups (.178 < P < .552).
CONCLUSION: ProRoot MTA has a similar sealing ability when placed as an apical
barrier with pluggers, paper points, or ultrasonic tips.
PMID- 25126640
TI - Longevity of silicate ceramic restorations.
AB - The demand for esthetic restorations has resulted in an increased use of dental
ceramics as a biocompatible and functionally sufficient alternative to
conventional restorative materials. Silicate ceramic restorations are widely used
for veneers, inlays, onlays, and crowns in dentistry. Long-term data are of
crucial importance to optimize clinical practice. The purpose of the present
article is to summarize data of the Innsbruck ceramic evaluation up to 261 months
with the focus on longevity and failure characteristics.
PMID- 25126641
TI - Geriatric dentistry: new challenges and new opportunities!
PMID- 25126642
TI - Criteria for the selection of restoration materials.
AB - Selection of the appropriate material for dental restoration has become more and
more difficult owing to the increasing variety of restoration materials. A
decision flow chart is presented to guide the treatment team (dentist and dental
technician) in the selection of the restoration material. This material selection
is based on the available interocclusal space, esthetic aspects (eg, brightness
value or translucency of the neighboring teeth), as well as clinical evidence
extracted from survival rates.
PMID- 25126643
TI - Prevalence of periodontal disease in patients with Familial Mediterranean Fever:
a cohort study from central Turkey.
AB - OBJECTIVE: The aim of this study was to compare the periodontal status in
patients with Familial Mediterranean Fever (FMF) and in those without this
disease. METHOD AND MATERIALS: 84 subjects clinically diagnosed with FMF and 75
systemically healthy controls, matched by age and gender, were recruited. All FMF
patients were on a regular daily colchicine treatment and during attack-free
periods. Gingival Index (GI), Plaque Index (PI), probing pocket depth (PD), and
clinical attachment level (CAL) were measured in all subjects. To evaluate
periodontal disease further, patients were stratified into fi ve groups.
Education information and smoking habits were recorded. RESULTS: The FMF patients
and healthy controls were comparable for age, gender, and smoking status (P>.05).
The FMF patients had significantly higher PI and GI values and lower PD and CAL
values than those of the control group (P<.05). However, there was no significant
difference among all groups in terms of periodontal disease severity (P>.05). In
the FMF-severe periodontitis group, higher PI and GI values were seen (P<.05).
However, there was no significant difference between the FMF-severe periodontitis
group and the controls with severe periodontitis regarding the PD and CAL values
(P>.05). CONCLUSION: Patients with FMF using colchicine did not manifest higher
attachment loss compared to age- and sex-matched systemically healthy controls.
PMID- 25126644
TI - Full-mouth composite rehabilitation of a mixed erosion and attrition patient: a
case report with v-shaped veneers and ultra-thin CAD/CAM composite overlays.
AB - Loss of tooth substance has become a common pathology in modern society. It is of
multifactorial origin, may be induced by a chemical process or by excessive
attrition, and frequently has a combined etiology. Particular care should be
taken when diagnosing the cause of dental tissue loss, in order to minimize its
impact. Several publications have proposed the use of minimally invasive
procedures to treat such patients in preference to traditional full-crown
rehabilitation. The use of composite resins, in combination with improvements in
dental adhesion, allows a more conservative approach. In this paper, we describe
the step-by-step procedure of full-mouth composite rehabilitation with v-shaped
veneers and ultra-thin computer-aided design/computer-assisted manufacture
(CAD/CAM)- generated composite overlays in a young patient with a combination of
erosion and attrition disorder.
PMID- 25126645
TI - Immediate postextraction implant with simultaneous buccal plate augmentation,
restored with lithium disilicate abutment and veneer: a clinical report.
AB - OBJECTIVE: To describe the successful use of biphasic calcium sulfate for
improving the buccal plate thickness in an immediate postextraction implant, and
its fi nal restoration with custom lithium disilicate abutment and veneer.
SUMMARY: A hopeless lateral incisor was replaced with an immediate postextraction
implant in conjunction with a buccal plate augmentation based on biphasic calcium
sulfate. Satisfactory soft tissue height and quality were maintained following
healing. The fi nal restoration managed the severely reduced prosthetic space due
to deep bite, and allowed an adhesive luting procedure.
PMID- 25126646
TI - Dental implants and osteomyelitis in a patient with osteopetrosis.
AB - Osteopetrosis (OP) is a rare genetic metabolic bone disorder characterized by
osteoclast dysfunction impairing bone resorption. Together with normal
osteoblastic activity this dysfunction promotes intense bone sclerosis with
reduction of marrow spaces as well as bone turnover. Maxillofacial complications
are common after tooth extraction. Osteomyelitis (OM) of the mandible occurs in
around 10% of the cases with OP. The purpose of this paper is to report the fi
rst case of OP treated with dental implants, and to describe the protocol used to
treat OM that developed after failure of one implant. The treatment of OM
included long-term use of antibiotics and marginal bone resection with a
piezoelectric device. Similar cases to confirm the efficacy of this treatment are
required.
PMID- 25126647
TI - Patients perceptions of recovery after maxillary sinus augmentation with a
minimally invasive implant device.
AB - OBJECTIVE: Patients' perceptions of recovery following sinus augmentation
procedures have scarcely been documented. The aim of the present prospective
pilot clinical study was to evaluate the patient's perception of immediate
postoperative recovery after sinus augmentation, using a minimally invasive
implant device. METHOD AND MATERIALS: Eighteen patients (8 men, 10 women),
average age 52 (median 48, range 38 to 72), who had been scheduled for sinus
augmentation procedures, were asked to enroll in a prospective clinical study. A
healthrelated quality-of-life questionnaire was given to the patient. The
questionnaire was designed to assess patient's perception of recovery in four
main areas: pain, oral function, general activity, and other symptoms. The
questionnaire was compared to the surgical chart that described the surgical
details and to the outcome. RESULTS: Patients' perceptions of postoperative
symptoms in the four tested areas: pain, oral function, general activity, and
other symptoms were mostly scored "not at all" or "very little" from
postoperative day (POD) 1. Most patients returned to work on POD 1. CONCLUSION:
The current results offer a preliminary indication that patients undergoing sinus
augmentation using a minimally invasive implant device can expect to experience
minimum discomfort and immediate return to everyday activity.
PMID- 25126648
TI - A comparison between histologic and clinical diagnoses of oral lesions.
AB - OBJECTIVE: The dentist has a fundamental role in the early diagnosis of lesions
of the oral cavity. The aim of this study was to establish the rate of erroneous
clinical diagnoses and whether a clinical diagnosis is enough. The study was
conducted to ascertain the overall accuracy of clinical diagnoses established by
dentists. STUDY DESIGN: The biopsy reports of 1,566 samples taken from 1,406
patients and examined at the Dental Outpatients Department of the University of
Padua from 1 January 2006 to 30 June 2012 were analyzed in order to compare the
presumptive clinical diagnosis with the fi nal diagnosis based on histology.
RESULTS: Overall, the dentists' clinical diagnoses were erroneous in 31.5% of
cases. These diagnostic errors pertained to 23.8% of the benign neoplasms, 78.9%
of the malignant neoplasms, and 17% of precancerous lesions. CONCLUSION: The
present report should not be interpreted as a criticism of the clinicians making
diagnostic errors but rather a confirmation of the policy to submit excised
tissues for histologic examination.
PMID- 25126649
TI - Fluorescent sensors for the basic metabolic panel enable measurement with a smart
phone device over the physiological range.
AB - The advanced functionality of portable devices such as smart phones provides the
necessary hardware to potentially perform complex diagnostic measurements in any
setting. Recent research and development have utilized cameras and data
acquisition properties of smart phones to create diagnostic approaches for a
variety of diseases or pollutants. However, in concentration measurements, such
as blood glucose, the performance of handheld diagnostic devices depends largely
on the sensing mechanism. To expand measurements to multiple components, often
necessary in medical tests, with a single diagnostic device, robust platform
based sensors are needed. Here, we developed a suite of dual wavelength
fluorescent sensors with response characteristics necessary to measure each
component of a basic metabolic panel, a common clinical measurement. Furthermore,
the response of these sensors could be measured with a simple optical setup to
convert a smart phone into a fluorescence measurement instrument. This approach
could be used as a mobile basic metabolic panel measurement system for point of
care diagnostics.
PMID- 25126650
TI - Fluorescence turn-on detection of Sn2+ in live eukaryotic and prokaryotic cells.
AB - Sn(2+) is usually added to toothpaste to prevent dental plaque and oral disease.
However, studies of its physiological role and bacteriostatic mechanism are
restricted by the lack of versatile Sn(2+) detection methods applicable to live
cells, including Streptococcus mutans. Here we report two Sn(2+) fluorescent
probes containing a rhodamine B derivative as a fluorophore, linked via the amide
moiety to N,N-bis(2-hydroxyethyl)ethylenediamine (R1) and tert-butyl carbazate
group (R2), respectively. These probes can selectively chelate Sn(2+) and show
marked fluorescence enhancement due to the ring open reaction of rhodamine
induced by Sn(2+) chelation. The probes have high sensitivity and selectivity for
Sn(2+) in the presence of various relevant metal ions. Particularly, both R1 and
R2 can target lysosomes, and R2 can probe Sn concentrations in lysosomes with
rather acidic microenvironment. Furthermore, these two probes have low toxicity
and can be used as imaging probes for monitoring Sn(2+) not only in live KB cells
(eukaryotic) but also in Streptococcus mutans cells (prokaryotic), which is a
useful tool to study the physiological function of Sn(2+) in biological systems.
PMID- 25126651
TI - Alkylation of benzene with carbon monoxide over Zn/H-ZSM-5 zeolite studied using
in situ solid-state NMR spectroscopy.
AB - Using in situ solid-state NMR spectroscopy we show that CO can act as an
alkylating reagent and react with benzene to produce toluene over a Zn/H-ZSM-5
zeolite. In the alkylation reaction, CO provides the methyl group of toluene via
a methoxy intermediate.
PMID- 25126652
TI - In situ generation of redox active peptides driven by selenoester mediated native
chemical ligation.
AB - Redox active peptides are generated through selenoester mediated native chemical
ligation (NCL). Distinct nanostructures, such as nanotubes to nanofibrillar
architectures, were observed for self-assembling soft materials.
PMID- 25126653
TI - Zinc-silylene complexes.
AB - Reactions of the chlorosilylene [PhC(N(t)Bu)2]SiCl (SiCl) and the aryl and alkyl
zincorganyls Zn(C5Me5)2, ZnPh2 and ZnEt2 resulted in the first Zn-silylene
complexes. In all reactions the chlorine atom of the silylene and organic groups
of the zinc atom are exchanged. By using Zn(C5Me5)2 and ZnPh2 one of the newly
formed silylene coordinates to the zinc atom to give [PhC(N(t)Bu)2(eta(1)
C5Me5)Si-Zn(eta(2)-C5Me5)Cl] and [PhC(N(t)Bu)2PhSi-ZnPh(MU-Cl)]2, respectively.
In contrast, the reaction of SiCl with ZnEt2 resulted due the reduced steric
demand of the silylene in the disilylene complex [PhC(N(t)Bu)2SiEt]2ZnCl2, in
which both ethyl-moieties are exchanged by chlorides and two newly formed ethyl
silylenes coordinate to the zinc atom.
PMID- 25126654
TI - Self-healable macro-/microscopic shape memory hydrogels based on supramolecular
interactions.
AB - A simple strategy is provided to construct novel supramolecular hydrogels with
both self-healing and shape memory properties. Starting from achieving self
healable hydrogel based on the dynamic interactions of phenylboronic acid
modified sodium alginate (Alg-PBA) and poly(vinyl alcohol) (PVA), further
formation of a complex of alginate with Ca(2+) renders this hydrogel with the
capability of shape memory at the macro-/microscopic scales.
PMID- 25126655
TI - Rhodium(II)-catalysed tandem aziridination and ring-opening: stereoselective
synthesis of functionalised tetrahydrofurans.
AB - Aziridines formed upon treatment of allylic carbamates and homoallylic sulfamates
with Rh(II) carboxylate catalysts under oxidative conditions are trapped by
suitably-disposed hydroxyl groups to give functionalised tetrahydrofurans.
PMID- 25126656
TI - Selective oxidations of activated alcohols in water at room temperature.
AB - Allylic and benzylic alcohols can be selectively oxidized to their corresponding
aldehydes or ketones in water containing nanoreactors composed of the designer
surfactant TPGS-750-M. The oxidation relies on catalytic amounts of CuBr, bpy,
and TEMPO, with N-methyl-imidazole; air is the stoichiometric oxidant.
PMID- 25126657
TI - Recent progress in the chemistry of endohedral metallofullerenes.
AB - Putting metal atoms or metallic clusters into fullerenes has generated a new
class of hybrid molecules, defined as endohedral metallofullerenes (EMFs),
possessing novel structures and fascinating properties which are different from
those of empty fullerenes. In particular, it has been revealed that the chemical
properties of the cage carbons of EMFs depend strongly on the nature of the
internal metallic species, such as their electronic configuration, location and
even motion. Since the first report describing the successful derivatization of
La@C82 in 1995, great efforts have been devoted to the chemical modification of
EMFs during the last two decades. Although earlier studies mainly focused on
readily available species such as M@C82, M2@C80 and M3N@C80 and the related
results have been systematically summarized in our previous review paper (Chem.
Commun., 2011, 47, 5942-5957), recent concerns about some relatively rare EMFs
have developed rapidly. Moreover, taking advantage of single crystal X-ray
crystallography, we can now clearly demonstrate the mutual influences between the
internal metallic species and the chemical behaviours of the surrounding cage
carbons, and the addends as well. In this article, we present recent achievements
in the chemical functionalization of EMFs, which were mainly published during the
last four years. For consistency, we will still pay special attention to the role
that the metals play in controlling the properties of the whole EMF molecules. In
this review, however, we will not only focus on concrete experimental results
such as X-ray crystallographic and NMR spectroscopic data but will also include
computational studies which have indeed enhanced our understanding of the
chemical properties of EMFs. Applicable materials based on EMFs are also
mentioned but are not discussed in detail.
PMID- 25126658
TI - In response.
PMID- 25126659
TI - Performance index: An expeditious tool to screen for improved drought resistance
in the Lathyrus genus.
AB - Some species of the Lathyrus genus are among the most promising crops for
marginal lands, with high resilience to drought, flood, and fungal diseases,
combined with high yields and seed nutritional value. However, lack of knowledge
on the mechanisms underlying its outstanding performance and methodologies to
identify elite genotypes has hampered its proper use in breeding. Chlorophyll a
fast fluorescence transient (JIP test), was used to evaluate water deficit (WD)
resistance in Lathyrus genus. Our results reveal unaltered photochemical values
for all studied genotypes showing resistance to mild WD. Under severe WD, two
Lathyrus sativus genotypes showed remarkable resilience maintaining the
photochemical efficiency, contrary to other genotypes studied. Performance index
(PIABS) is the best parameter to screen genotypes with improved performance and
grain production under WD. Moreover, we found that JIP indices are good
indicators of genotypic grain production under WD. Quantum yield of electron
transport (phiEo) and efficiency with which trapped excitons can move electrons
further than QA (psi0) revealed as important traits related to improved
photosynthetic performance and should be exploited in future Lathyrus germplasm
improvements. The JIP test herein described showed to be an expeditious tool to
screen and to identify elite genotypes with improved drought resistance.
PMID- 25126660
TI - Retraction. Removal notice to "Regional cerebral oxygen saturation on hospital
arrival is a potential novel predictor of neurological outcomes at hospital
discharge in patients with out-of-hospital cardiac arrest" [Resuscitation 83
(2012) 46-50].
PMID- 25126661
TI - Mental health: Stressed students reach out for help.
PMID- 25126663
TI - Local photodynamic therapy delays recurrence of equine periocular squamous cell
carcinoma compared to cryotherapy.
AB - OBJECTIVE: (i) To report the successful treatment of 10 cases of equine
periocular squamous cell carcinoma (PSCC) with surgical excision and photodynamic
therapy (PDT) using verteporfin. (ii) To evaluate time to first tumor recurrence
between PDT-treated horses and horses treated with surgical excision and
cryotherapy. METHODS: A total of 24 equine PSCC cases were included: group 1 (n =
14) had excision and cryotherapy (1993-2003), group 2 (n = 10), excision and
local PDT (2006-2010). Evaluated data: signalment, treatment method, tumor
location, size, and time to first recurrence. Groups were compared via chi-square
test for categorical variables and Wilcoxon rank-sum test for numeric variables.
Time to tumor recurrence was examined using Kaplan-Meier product-limit survival
analysis. RESULTS: Of 24 cases, nine breeds were affected. Mean age at treatment
in years: 14 (range 5-24) in group 1; 11 (range 8-18) in group 2. Median tumor
size: 163 mm2 (range 20-625 mm2) in group 1; 195 mm2 (range 45-775 mm2) in group
2. Signalment, tumor laterality, and size were not significantly different
between groups. Time to recurrence was significantly different between groups
(Logrank test, P = 0.0006). In group 1, 11/14 horses had tumor regrowth with
median time to recurrence in months: 10 (range 1-44). In group 2 (minimum follow
up of 25 months; range 25-50), no horse demonstrated tumor recurrence after one
treatment with excision and PDT. CONCLUSIONS: This represents the first report of
local PDT using verteporfin for treatment of equine PSCC. Following surgery, the
likelihood of tumor recurrence was significantly reduced with local PDT compared
with cryotherapy.
PMID- 25126662
TI - Profiling the repertoire of T-cell receptor beta-chain variable genes in
peripheral blood lymphocytes from subjects who have recovered from acute
hepatitis B virus infection.
AB - The profile of T-cell receptor beta-chain variable (TRBV) genes usually skews in
subjects with virus infection or cancer. The gene melting spectral pattern (GMSP)
can be used to determine the profile of the TRBV gene family. To explore the
portrait of the TRBV family in peripheral blood lymphocytes from subjects who
have recovered from acute hepatitis B virus infection (AHI), peripheral blood
mononuclear cells (PBMCs) were separated and further sorted into CD4+ and CD8+ T
cell subsets. The molecular features of the TRBV complementary determining region
3 (CDR3) motifs were determined using GMSP analysis. When aGMSP profile showed a
single peak, the monoclonally expanded TRBV gene was cloned and sequenced. Skewed
expansions of multiple TRBV genes were observed among the CD4+ and CD8+ T-cell
subsets and the PBMCs. The frequency of monoclonally expanded TRBV genes in the
CD8+ T-cell subset was significantly higher than that of the CD4+ T-cell subset
and the PBMCs. Compared to other members of the TRBV gene family, TRBV11, BV15
and BV20 were predominantly expressed in the repertoire of peripheral blood
lymphocytes in recovered AHI subjects. The relatively conserved amino acid motifs
of TRBV5.1 and BV20 CDR3 were also detected in the CD4+ and CD8+ T-cell subsets.
These results demonstrate the presence of multiple biased TRBV families in
recovered AHI subjects. TRBV11, BV15 and BV20, especially from the CD8+ T-cell
subset, may be relevant to the pathogenesis of subjects with AHI. The
preferentially selected TRBV5.1 and BV20 with the relatively conserved CDR3 motif
may be potential targets for personalized treatments of chronic HBV infection.
PMID- 25126664
TI - Histopathological features of equine superficial, nonhealing, corneal ulcers.
AB - OBJECTIVE: To evaluate corneal changes associated with chronic, nonhealing,
superficial, corneal ulcers in horses via common histopathological stains.
DESIGN: Retrospective study. ANIMALS: Twenty-four horses diagnosed with chronic,
nonhealing, superficial, corneal ulceration. METHODS: The medical records of
horses evaluated at North Carolina State University's Veterinary Teaching
Hospital (NCSU-VTH) from 2005 to 2011, diagnosed with a chronic, nonhealing,
superficial, corneal ulcer and treated with superficial keratectomy (SK) were
reviewed. Inclusion criteria were superficial corneal ulceration, no cellular
infiltration via slit-lamp biomicroscopy, no microorganisms evident on corneal
cytology, and acquisition of samples for aerobic bacterial and common fungal
cultures. Corneal tissue samples were evaluated histopathologically for the
presence or absence of a nonadherent epithelial 'lip', epithelial dysmaturity,
intraepithelial inflammatory cells, an acellular hyaline zone in the anterior
stroma, and stromal inflammatory cells, fibrosis and vascularization. RESULTS: In
the majority of analyzed samples, epithelial cells adjacent to the ulcerated site
showed nonadherence to the basement membrane and dysmaturity. Intraepithelial
inflammatory cell infiltration was uncommon. Histopathological features of an
anterior stromal hyaline zone, intrastromal inflammation, fibrosis and
vascularization were variably present. CONCLUSIONS: The most consistent
histopathological characteristics of equine chronic, nonhealing, superficial,
corneal ulcers include epithelial nonadherence, epithelial dysmaturity and mild
to moderate stromal inflammation; however, one set of histopathological
characteristics does not definitively define this syndrome in horses.
Additionally, the anterior stromal acellular hyaline zone commonly cited in
canine spontaneous chronic corneal epithelial defects (SCCED) is not a consistent
finding in equine corneas.
PMID- 25126665
TI - Suberoylanilide hydroxamic acid (vorinostat): its role on equine corneal
fibrosis and matrix metalloproteinase activity.
AB - OBJECTIVE: To explore the effect of suberoylanilide hydroxamic acid (SAHA) (i) on
corneal fibroblast differentiation, morphology, and viability; and (ii) on the
expression levels of matrix metalloproteinases (MMPs) 2 and 9 using an in vitro
model of equine corneal fibrosis. PROCEDURE: Healthy donor corneas were used to
generate primary cultures of equine corneal fibroblasts. The fibroblasts were
exposed to 5 ng/mL TGFbeta1 to induce myofibroblast formation. The cultures were
treated with either 5 MUm or 10 MUm SAHA for 72 h in the presence of TGFbeta1.
Real-time PCR and immunocytochemistry were used to determine the antifibrotic
efficacy of SAHA by quantifying alpha-smooth muscle actin (alphaSMA), a marker of
myofibroblast formation and fibrosis. Real-time PCR was used to determine the
effects of SAHA on MMP2 and MMP9 expression. Cytotoxicity of SAHA was evaluated
with phase contrast microscopy and trypan blue exclusion assays. RESULTS:
Suberoylanilide hydroxamic acid (SAHA) significantly attenuated TGFbeta1-induced
differentiation of equine fibroblasts to myofibroblasts as indicated by 3- to 3.5
fold (P < 0.001) decrease in alphaSMA mRNA and 86-88% (P < 0.001) decrease in
alphaSMA+ immunocytochemical staining. SAHA treatment also resulted in 4.5- to
5.5-fold (P < 0.01) decrease in MMP9 expression. A dose-dependent bimodal effect
of SAHA on MMP2 expression was noted (3.5-fold increase with 5 MUm dose; 0.5-fold
decrease with 10 MUm dose). No change in fibroblast viability was observed with a
5 MUm SAHA dose, whereas a 10 MUm dose resulted in a moderate 17% decrease in
cell viability. CONCLUSIONS: Suberoylanilide hydroxamic acid (SAHA) can
effectively inhibit TGFbeta-induced differentiation of equine corneal fibroblasts
to myofibroblasts and modulates MMP production in vitro.
PMID- 25126666
TI - Gold-thiolate ring as a protecting motif in the Au20(SR)16 nanocluster and
implications.
AB - Understanding how gold nanoclusters nucleate from Au(I)SR complexes necessitates
the structural elucidation of nanoclusters with decreasing size. Toward this
effort, we herein report the crystal structure of an ultrasmall nanocluster
formulated as Au20(TBBT)16 (TBBT = SPh-t-Bu). The structure features a vertex
sharing bitetrahedral Au7 kernel and an unprecedented "ring" motif-Au8(SR)8. This
large ring protects the Au7 kernel through strong Auring-Aukernel bonding but
does not involve S-Aukernel bonding, in contrast to the common "staple" motifs in
which the S-Aukernel bonding is dominant but the Austaple-Aukernel interaction is
weak (i.e., aurophilic). As the smallest member in the TBBT "magic series",
Au20(TBBT)16, together with Au28(TBBT)20, Au36(TBBT)24, and Au44(TBBT)28, reveals
remarkable size-growth patterns in both geometric structure and electronic
nature. Moreover, Au20(TBBT)16, together with the Au24(SR)20 and Au18(SR)14
nanoclusters, forms a "4e" nanocluster family, which illustrates a trend of
shrinkage of bitetrahedral kernels from Au8(4+) to Au7(3+) and possibly to
Au6(2+) with decreasing size.
PMID- 25126667
TI - Bioelectronic tongue using heterodimeric human taste receptor for the
discrimination of sweeteners with human-like performance.
AB - The sense of taste helps humans to obtain information and form a picture of the
world by recognizing chemicals in their environments. Over the past decade, large
advances have been made in understanding the mechanisms of taste detection and
mimicking its capability using artificial sensor devices. However, the detection
capability of previous artificial taste sensors has been far inferior to that of
animal tongues, in terms of its sensitivity and selectivity. Herein, we developed
a bioelectronic tongue using heterodimeric human sweet taste receptors for the
detection and discrimination of sweeteners with human-like performance, where
single-walled carbon nanotube field-effect transistors were functionalized with
nanovesicles containing human sweet taste receptors and used to detect the
binding of sweeteners to the taste receptors. The receptors are heterodimeric G
protein-coupled receptors (GPCRs) composed of human taste receptor type 1 member
2 (hTAS1R2) and human taste receptor type 1 member 3 (hTAS1R3), which have
multiple binding sites and allow a human tongue-like broad selectivity for the
detection of sweeteners. This nanovesicle-based bioelectronic tongue can be a
powerful tool for the detection of sweeteners as an alternative to labor
intensive and time-consuming cell-based assays and the sensory evaluation panels
used in the food and beverage industry. Furthermore, this study also allows the
artificial sensor to exam the functional activity of dimeric GPCRs.
PMID- 25126670
TI - Chemistry makes graphene beyond graphene.
AB - Although graphene is extremely inert in chemistry because of the giant
delocalized pi electron system, various methods have been developed to achieve
its efficient chemical modification. Covalent chemistry is effective to modulate
the physical properties of graphene. By converting the sp(2) hybridized carbon
atoms to sp(3) ones, new two-dimensional (2D) materials and 2D superlattices with
fascinating features beyond mother graphene could be built from the graphene
scaffold, greatly expanding the graphene family and its attraction. In this
Perspective, the power of covalent chemistry is demonstrated from the viewpoint
of tailoring graphene's energy band structure as well as creating new 2D
materials and 2D superlattices. A specific focus is laid on the general
consideration and understanding of covalent graphene chemistry toward electronic
devices and material science.
PMID- 25126671
TI - Manganese nanoparticles: impact on non-nodulated plant as a potent enhancer in
nitrogen metabolism and toxicity study both in vivo and in vitro.
AB - Mung bean plants were grown under controlled conditions and supplemented with
macro- and micronutrients. The objective of this study was to determine the
response of manganese nanoparticles (MnNP) in nitrate uptake, assimilation, and
metabolism compared with the commercially used manganese salt, manganese sulfate
(MS). MnNP was modulated to affect the assimilatory process by enhancing the net
flux of nitrogen assimilation through NR-NiR and GS-GOGAT pathways. This study
was associated with toxicological investigation on in vitro and in vivo systems
to promote MnNP as nanofertilizer and can be used as an alternative to MS. MnNP
did not impart any toxicity to the mice brain mitochondria except in the partial
inhibition of complex II-III activity in ETC. Therefore, mitochondrial
dysfunction and neurotoxicity, which were noted by excess usage of elemental
manganese, were prevented. This is the first attempt to highlight the nitrogen
uptake, assimilation, and metabolism in a plant system using a nanoparticle to
promote a biosafe nanomicronutrient-based crop management.
PMID- 25126672
TI - L1 cell adhesion molecule is a strong predictor for distant recurrence and
overall survival in early stage endometrial cancer: pooled PORTEC trial results.
AB - BACKGROUND: L1 cell adhesion molecule (L1CAM) expression has been implicated as
risk factor for disease recurrence in endometrial cancer (EC), most likely due to
its role in promoting tumour cell motility. We tested the performance of L1CAM
expression in predicting the risk of recurrence in the randomised post operative
radiation therapy in endometrial carcinoma (PORTEC)-1 and -2 trials. METHODS: In
the PORTEC trials, stage I EC patients were randomised to external beam
radiotherapy (EBRT) versus no additional treatment (PORTEC-1, n=714), or to EBRT
versus vaginal brachytherapy (PORTEC-2, n=427). Tumour samples of 865 (75.8%)
patients were available for L1CAM expression analysis by immunohistochemistry. An
established scoring system for EC was used, with >10% L1CAM staining defined as
positive. RESULTS: Positive L1CAM expression was significantly correlated with
risk of distant recurrence, with a hazard ratio (HR) of 5.1 (95% confidence
interval (CI) 3.1-8.7) but not with vaginal relapse, while a trend for pelvic
nodal relapse was found. Tumours with the highest expression levels (>50%
positive) had the strongest risk of distant recurrence (HR 5.3, CI 2.7-10.4). In
multivariate Cox analysis with the risk factors age, depth of invasion, grade,
lympho-vascular space invasion (LVSI) and treatment, L1CAM expression remained an
independent prognostic factor for distant recurrence (HR 3.5, CI 1.92-6.30) and
overall survival (HR 2.1, CI 1.41-2.98). CONCLUSION: L1CAM expression is a strong
independent predictor for distant recurrence and overall survival in stage I
endometrial cancer. These results warrant prospective validation of L1CAM as
marker for selecting patients who could benefit from more extensive diagnostic
and/or therapeutic procedures.
PMID- 25126673
TI - Enantioselective synthesis of the predominant AB ring system of the Schisandra
nortriterpenoid natural products.
AB - An enantioselective synthesis of the AB ring system common to the majority of the
Schisandra nortriterpenoid natural products is reported. Key steps include a
stereospecific ring opening of a trisubstituted epoxide and the use of a beta
lactone to enable installation of the gem-dimethyl functionality of the B ring.
An acetalization strategy played a key role in a late-stage biomimetic AB ring
bicyclization.
PMID- 25126676
TI - Complementarity of EIS and SPR to reveal specific and nonspecific binding when
interrogating a model bioaffinity sensor; perspective offered by plasmonic based
EIS.
AB - The present work compares the responses of a model bioaffinity sensor based on a
dielectric functionalization layer, in terms of specific and nonspecific binding,
when interrogated simultaneously by Surface Plasmon Resonance (SPR), non-Faradaic
Electrochemical Impedance Spectroscopy (EIS), and Plasmonic based-EIS (P-EIS).
While biorecognition events triggered a sensitive SPR signal, the related EIS
response was rather negligible. Contrarily, even a limited nonspecific adsorption
onto the surface of the metallic electrode, allowed by the intrinsic imperfect
compactness of the functionalization layers, was signaled by EIS and not by SPR.
The source of this finding has been addressed from both theoretical and
experimental perspectives, demonstrating that EIS signals are mainly sensitive to
adsorptions that alter the current pathway through defects of the
functionalization layer exposing the electrode. These observations are of
importance for those developing biosensors analyzed by SPR, EIS, or the novel
combination of the two methods (P-EIS). A possible application of the observed
complementarity of the two methods, namely assessment of sample purity in respect
to a target analyte is highlighted. Moreover, the possibility of false-positive
EIS responses (determined by nonspecific binding) when assessing samples
containing complex matrices or consisting of small molecular weight analytes is
emphasized.
PMID- 25126675
TI - Camouflage effects following resin infiltration of postorthodontic white-spot
lesions in vivo: One-year follow-up.
AB - OBJECTIVE: To assess camouflage effects by concealment of postorthodontic white
spot lesions (WSLs) to sound adjacent enamel (SAE) achieved over 12 months with
resin infiltration (Icon, DMG, Hamburg, Germany). METHODS: Twenty subjects (trial
teeth nteeth = 111) who had received resin infiltration treatment of noncavitated
postorthodontic WSLs were contacted for a 1-year follow-up assessment of CIE
L*a*b* colors (T12). Color and lightness (CIE-L*a*b*) data for WSLs and SAE were
compared to baseline data assessed before infiltration (T0) and those assessed
after 6 months (T6), using a spectrophotometer. The target parameter was the
difference between the summarized color and lightness values (DeltaEWSL/SAE).
Intergroup (WSL, SAE) and intertime comparisons (T0 vs T6, T12) were performed
using paired t-tests at a significance level of alpha = 5%. RESULTS: Nine
subjects (trial teeth nteeth = 49; male/female ratio 5/4; age range 13-19 years)
were available at T12. After the highly significant reduction of DeltaEWSL/SAE
discrepancies between T0 and T6, analysis of 12-month records revealed color and
lightness discrepancy of WSL vs SAE that was significantly decreased compared
with baseline, indicating an assimilation of WSL color to SAE appearance after
infiltration, while an additional reduction of discrepancies between T6 and T12
was not significant. CONCLUSION: As color and lightness characteristics of the
Icon infiltrant as well as the esthetic camouflage effects achieved by WSL
infiltration were not altered significantly or clinically relevant after 12
months, the method of resin infiltration can be recommended for an enduring
esthetic improvement of postorthodontic WSL.
PMID- 25126677
TI - James F. Jerger, PhD, responds to five questions.
PMID- 25126674
TI - Atypical cell populations associated with acquired resistance to cytostatics and
cancer stem cell features: the role of mitochondria in nuclear encapsulation.
AB - Until recently, acquired resistance to cytostatics had mostly been attributed to
biochemical mechanisms such as decreased intake and/or increased efflux of
therapeutics, enhanced DNA repair, and altered activity or deregulation of target
proteins. Although these mechanisms have been widely investigated, little is
known about membrane barriers responsible for the chemical imperviousness of cell
compartments and cellular segregation in cytostatic-treated tumors. In highly
heterogeneous cross-resistant and radiorefractory cell populations selected by
exposure to anticancer agents, we found a number of atypical recurrent cell types
in (1) tumor cell cultures of different embryonic origins, (2) mouse xenografts,
and (3) paraffin sections from patient tumors. Alongside morphologic
peculiarities, these populations presented cancer stem cell markers, aberrant
signaling pathways, and a set of deregulated miRNAs known to confer both stem
cell phenotypes and highly aggressive tumor behavior. The first type, named
spiral cells, is marked by a spiral arrangement of nuclei. The second type,
monastery cells, is characterized by prominent walls inside which daughter cells
can be seen maturing amid a rich mitochondrial environment. The third type,
called pregnant cells, is a giant cell with a syncytium-like morphology, a main
nucleus, and many endoreplicative functional progeny cells. A rare fourth cell
type identified in leukemia was christened shepherd cells, as it was always
associated with clusters of smaller cells. Furthermore, a portion of resistant
tumor cells displayed nuclear encapsulation via mitochondrial aggregation in the
nuclear perimeter in response to cytostatic insults, probably conferring
imperviousness to drugs and long periods of dormancy until nuclear eclosion takes
place. This phenomenon was correlated with an increase in both intracellular and
intercellular mitochondrial traffic as well as with the uptake of free
extracellular mitochondria. All these cellular disorders could, in fact, be found
in untreated tumor cells but were more pronounced in resistant entities,
suggesting a natural mechanism of cell survival triggered by chemical injury, or
a primitive strategy to ensure stemming, self-renewal, and differentiation under
adverse conditions, a fact that may play a significant role in chemotherapy
outcomes.
PMID- 25126679
TI - Aural rehabilitation through music workshops for cochlear implant users.
AB - BACKGROUND: It has been reported that after speech perception, music appreciation
is the second most commonly expressed requirement among cochlear implant (CI)
recipients. Certain features of music are known to be more readily accessible;
however, provision of music rehabilitation for adult CI users is limited.
PURPOSE: A series of music workshops were organized to (1) enable attendees to
explore which aspects of music they are able to perceive and appreciate; (2)
raise awareness of listening strategies, technology, and rehabilitation resources
for music; and (3) develop ideas, and prototype software, for inclusion in a
music rehabilitation program. The therapeutic value of music workshops was
concurrently investigated. RESEARCH DESIGN: A qualitative, longitudinal study was
used. Two consultation meetings were held before a series of nine music workshops
that occurred over a period of 5 mo. STUDY SAMPLE: Five adult CI users
participated in consultations before the workshops. Twenty-eight adult CI users
from the South of England Cochlear Implant Centre attended at least one of the
workshops. INTERVENTION: Participants could attend as many workshops as they
wished. Each workshop lasted between 2 to 2.5 hr and included individual computer
based and group activities. DATA COLLECTION AND ANALYSIS: Responses to open-ended
questions were transcribed in the consultation meetings and used to develop
workshop activities. A preworkshop survey was used to determine attendees'
aspirations and expectations. Postworkshop surveys were used to qualitatively and
quantitatively evaluate attendees' immediate reactions to the workshop content,
software, and perceived benefits. A 2-month, postworkshop survey evaluated the
longer-term impact of the workshops. RESULTS: Overall reaction to the workshops
and prototype software was positive. All attendees indicated that they
anticipated changing how they engaged with music as a result of the workshops,
and data from the preworkshop and postworkshop surveys suggest a positive change
in listening habits. CONCLUSIONS: The workshops proved to be an effective means
of simultaneously encouraging music exploration in a social and safe environment
and obtaining feedback on prototype rehabilitation materials. Survey data
suggested that through group listening and practical activities, certain aspects
of music can be accessible and rewarding through a CI, leading to positive
changes in attitude and behavior toward music.
PMID- 25126680
TI - The influence of aging on interaural asymmetries in middle latency response
amplitude.
AB - BACKGROUND: Auditory-evoked potentials (EPs) provide a more objective assessment
of central auditory nervous system (CANS) dysfunction when compared to behavioral
measures because they do not require a behavioral response (Anderson and Kraus,
2010). In this regard, the middle latency response (MLR) has been considered an
important component of CANS assessment (Jerger et al, 1988); however, its large
within-group variability limits its usefulness (Musiek et al, 1999). It has been
argued that performing intratest calculations on the MLR (e.g., difference in EP
amplitude when stimulating the left ear versus the right ear) can reduce the
within-group variability of the MLR and enhance its clinical usefulness (Musiek
et al, 1999; Weihing et al, 2012). To date, it has not been investigated how well
these MLR intratest measures reduce within-group variability in adults of various
ages, nor has it been shown that these intratest measures are sensitive to aging
related changes in the CANS. PURPOSE: The two primary goals of the present study
were (1) to determine if calculating an intratest MLR measure, the difference in
MLR Na-Pa peak-to-peak amplitude on left versus right ear stimulation (i.e., "ear
effects"), will reduce within-group variability in adults of various ages; and
(2) to determine if ear effect magnitude will change as a function of aging. Ear
effects were measured in both quiet and in noise to determine if the addition of
noise enhanced any age-related-effects. RESEARCH DESIGN: A cross-sectional study
was conducted. STUDY SAMPLE: The researchers studied 30 adults ranging in age
from 20-80 yr with hearing sensitivity of 25 dB HL or better at the octave
frequencies from 500-2000 Hz, and no history of neurologic issues. Adults were
assigned to one of three age groups based on their chronological age, which were
young adults, middle-aged adults, and older adults. DATA COLLECTION AND ANALYSIS:
MLRs were acquired using a Nicolet Spirit 2000 during a single laboratory visit.
To determine if within-group variability decreased significantly with ear
effects, variability for absolute amplitude measures was compared to ear effect
variability using the Pitman t-test. To examine potential effects of background
noise and aging, data were analyzed using a mixed-factorial analysis of variance
with the within-subjects factor "background noise" and the between-subjects
factor "age group." RESULTS: Within-group variability was significantly reduced
by calculating ear effects for the youngest group only. Additionally, the oldest
adults in the present sample showed significantly larger ear effects than younger
and middle-aged adults. This effect did not appear to be a result of differences
in peripheral hearing sensitivity. Finally, introducing noise into the paradigm
did not influence the observed effects. CONCLUSIONS: Ear effects become larger in
older adults possibly as a result of age-related changes in the subcortical
and/or cortical generators of the MLR. Failure of the ear effect calculation to
reduce within-group variability in the middle-aged and older adults suggests that
interaural asymmetries in MLR amplitude become more variable across participants
who are older than 50 yr. Information obtained from this measure may benefit the
development of treatment plans for older adults with hearing difficulties.
PMID- 25126681
TI - Music therapy for chronic tinnitus: variability of tinnitus pitch in the course
of therapy.
AB - BACKGROUND: In general, tinnitus pitch has been observed to be variable across
time for most patients experiencing tinnitus. Some tinnitus therapies relate to
the dominant tinnitus pitch in order to adjust therapeutic interventions. As
studies focusing on tinnitus pitch rarely conduct consecutive pitch matching in
therapeutic settings, little is known about the course and variability of
tinnitus pitch during therapeutic interventions. PURPOSE: The purpose of this
study was to investigate the variability and development of tinnitus pitch in the
course of therapeutic interventions. Tinnitus pitch was suspected to be highly
variable. RESEARCH DESIGN: The researchers conducted a descriptive, retrospective
analysis of data. STUDY SAMPLE: A total of 175 adult patients experiencing
chronic tinnitus served as participants. All patients had received a neuro-music
therapy according to the "Heidelberg Model of Music Therapy for Chronic
Tinnitus." DATA COLLECTION AND ANALYSIS: During therapeutic interventions lasting
for 5 consecutive days, the individual tinnitus frequency was assessed daily by
means of a tinnitus pitch-matching procedure. The extent of variability in
tinnitus pitch was calculated by mean ratios of frequencies between subsequent
tinnitus measurements. Analysis of variance of repeated measures and post hoc
paired samples t-tests were used for comparison of means in tinnitus frequencies,
and the test-retest reliability of measurements was obtained by the Pearson
product-moment correlation coefficient. RESULTS: Tinnitus pitch displayed a
variability of approximately 3/5 to 4/5 octaves per day. Overall, the mean
frequency declined in the course of the therapy. Detailed analysis revealed three
groups of patients with diverging tinnitus progression. The test-retest
reliability between assessments turned out to be robust (r = 0.74 or higher).
CONCLUSIONS: Considerable variation in tinnitus pitch was found. Consequently, a
frequent rechecking of tinnitus frequency is suggested during frequency-specific
acoustic stimulation in order to train appropriate frequency bands.
PMID- 25126682
TI - Normative sweep frequency impedance measures in healthy neonates.
AB - BACKGROUND: Diagnosing middle ear disorders in neonates is a challenging task for
both audiologists and otolaryngologists. Although high-frequency (1000 Hz)
tympanometry and acoustic stapedial reflex tests are useful in diagnosing middle
ear problems in this age group, they do not provide information about the
dynamics of the middle ear in terms of its resonance frequency (RF) and mobility.
The sweep frequency impedance (SFI) test can provide this information, which may
assist in the diagnosis of middle ear dysfunction in neonates. PURPOSE: This
study aimed to investigate the feasibility of testing neonates using the SFI
technique, establish normative SFI data for RF and mobility of the middle ear in
terms of changes in sound pressure level (?SPL in dB), and describe the dynamics
of the middle ear in healthy Australian neonates. STUDY SAMPLE: A prospective
sample of 100 neonates (58 males, 42 females) with a mean gestational age of 39.3
wk (SD = 1.3 wk; range = 38-42 wk), who passed all three tests, namely, automated
auditory brainstem response, transient evoked otoacoustic emissions, and 1000 Hz
tympanometry, were included in this study. DATA COLLECTION AND ANALYSIS: A SFI
research prototype was used to collect the data. First, the SPL in the ear canal
was measured as a probe-tone frequency was swept from 100-2000 Hz with the ear
canal static pressure held constant at 200 daPa. Then, this measurement was
repeated with the static pressure reduced in 50 daPa steps to -200 daPa.
Additional measurement was also performed at the static pressure, where the peak
of the 1000 Hz tympanogram occurred. A graph showing the variation of SPL against
frequency at all static pressures was plotted. From this graph, the RF and ?SPL
at tympanometric peak pressure (TPP) were determined. Descriptive statistics and
an analysis of variance (ANOVA) were applied to the RF and ?SPL data with gender
and ear as independent variables. RESULTS: The results showed two resonance
regions of the outer/middle ear with the high RF (mean = 1236 Hz; 90% range: 830
1518 Hz) being approximately equal to four times that of the low RF (mean = 287
Hz; 90% range = 209-420 Hz). The low RF was more easily identifiable than the
high RF. The ?SPL at the low RF (mean = 8.2 dB; 90% range = 3.4-13 dB) was
greater than that at the high RF (mean = 5.0 dB; 90% range = 1.5-8.1 dB). There
were no significant differences or interactions between genders and ears.
CONCLUSION: The study showed that the SFI is a feasible test of middle ear
function in neonates. The SFI results revealed two regions of resonance with the
lower resonance (287 Hz) possibly related to the movements of the outer ear canal
wall and higher resonance (1236 Hz) related to the resonance of the middle ear.
The normative data developed in this study will be useful in evaluating outer and
middle ear function in neonates.
PMID- 25126683
TI - Speech-on-speech masking with variable access to the linguistic content of the
masker speech for native and nonnative english speakers.
AB - BACKGROUND: Masking release for an English sentence-recognition task in the
presence of foreign-accented English speech compared with native-accented English
speech was reported in Calandruccio et al (2010a). The masking release appeared
to increase as the masker intelligibility decreased. However, it could not be
ruled out that spectral differences between the speech maskers were influencing
the significant differences observed. PURPOSE: The purpose of the current
experiment was to minimize spectral differences between speech maskers to
determine how various amounts of linguistic information within competing speech
Affiliationect masking release. RESEARCH DESIGN: A mixed-model design with within
subject (four two-talker speech maskers) and between-subject (listener group)
factors was conducted. Speech maskers included native-accented English speech and
high-intelligibility, moderate-intelligibility, and low-intelligibility Mandarin
accented English. Normalizing the long-term average speech spectra of the maskers
to each other minimized spectral differences between the masker conditions. STUDY
SAMPLE: Three listener groups were tested, including monolingual English speakers
with normal hearing, nonnative English speakers with normal hearing, and
monolingual English speakers with hearing loss. The nonnative English speakers
were from various native language backgrounds, not including Mandarin (or any
other Chinese dialect). Listeners with hearing loss had symmetric mild sloping to
moderate sensorineural hearing loss. DATA COLLECTION AND ANALYSIS: Listeners were
asked to repeat back sentences that were presented in the presence of four
different two-talker speech maskers. Responses were scored based on the key words
within the sentences (100 key words per masker condition). A mixed-model
regression analysis was used to analyze the difference in performance scores
between the masker conditions and listener groups. RESULTS: Monolingual English
speakers with normal hearing benefited when the competing speech signal was
foreign accented compared with native accented, allowing for improved speech
recognition. Various levels of intelligibility across the foreign-accented speech
maskers did not influence results. Neither the nonnative English-speaking
listeners with normal hearing nor the monolingual English speakers with hearing
loss benefited from masking release when the masker was changed from native
accented to foreign-accented English. CONCLUSIONS: Slight modifications between
the target and the masker speech allowed monolingual English speakers with normal
hearing to improve their recognition of native-accented English, even when the
competing speech was highly intelligible. Further research is needed to determine
which modifications within the competing speech signal caused the Mandarin
accented English to be less effective with respect to masking. Determining the
influences within the competing speech that make it less effective as a masker or
determining why monolingual normal-hearing listeners can take advantage of these
differences could help improve speech recognition for those with hearing loss in
the future.
PMID- 25126685
TI - Pediatric hearing aid use: how can audiologists support parents to increase
consistency?
AB - BACKGROUND: Children need consistent access to the full range of speech sounds
for spoken language development, making daily hearing aid management a
fundamental component of effective intervention. In addition to receiving
services from professionals with expertise in childhood hearing loss, parents
play a central role in the intervention process. However, parents can experience
an array of barriers and challenges in learning to cope with the demands of daily
management. Feedback about hearing aid use time might offer parents insight into
challenges and lead to the identification of strategies to increase use,
optimizing child outcomes. PURPOSE: This exploratory study had 2 primary
purposes: (1) to examine hearing aid use time for a cohort of children 7 mo to 6
yr of age and (2) to examine whether hearing aid use time increased when parents
were given periodic objective feedback (i.e., data-logging results) about average
daily use time. RESEARCH DESIGN: A retrospective chart review was used to collect
data on eligible participants. RESULTS: Findings for 29 children (7 mo to 6 yr of
age) revealed variability in hours of hearing aid use and an increase in hours of
use with age and severity of hearing loss. Reports of typical hearing aid use
from seven parents revealed that parents overestimated use by an average of 3.36
hr. Review of challenges reported revealed issues with retention, awareness of
the effect of nonuse on average daily access to sound, and lack of perceived
benefit of hearing aid use. Hearing aid use increased with communication about
data logging for some, but not all, parents. CONCLUSIONS: For effective
integration of essential hearing aid management skills into the daily lives of
primary caregivers, audiologists must consider caregiver needs in the overall
child management and monitoring plan. The ability to optimize child outcomes
might depend in part on the extent audiologists embrace family-centered services,
engage in collaborative problem solving, and support parents in applying
individualized strategies.
PMID- 25126684
TI - Effect of different signal-processing options on speech-in-noise recognition for
cochlear implant recipients with the cochlear CP810 speech processor.
AB - BACKGROUND: Difficulty understanding speech in the presence of background noise
is a common report among cochlear implant (CI) recipients. Several speech
processing options designed to improve speech recognition, especially in noise,
are currently available in the Cochlear Nucleus CP810 speech processor. These
include adaptive dynamic range optimization (ADRO), autosensitivity control
(ASC), Beam, and Zoom. PURPOSE: The purpose of this study was to evaluate CI
recipients' speech-in-noise recognition to determine which currently available
processing option or options resulted in best performance in a simulated
restaurant environment. RESEARCH DESIGN: Experimental study with one study group.
The independent variable was speech-processing option, and the dependent variable
was the reception threshold for sentences score. STUDY SAMPLE: Thirty-two adult
CI recipients. INTERVENTION: Eight processing options were tested: Beam, Beam +
ASC, Beam + ADRO, Beam + ASC + ADRO, Zoom, Zoom + ASC, Zoom + ADRO, and Zoom +
ASC + ADRO. DATA COLLECTION AND ANALYSIS: Participants repeated Hearing in Noise
Test sentences presented at a 0 degrees azimuth, with R-Space restaurant noise
presented from a 360 degrees eight-loudspeaker array at 70 dB sound pressure
level. A one-way repeated-measures analysis of variance was used to analyze
differences in Beam options, Zoom options, and Beam versus Zoom options. RESULTS:
Among the Beam options, Beam + ADRO was significantly poorer than Beam only, Beam
+ ASC, and Beam + ASC + ADRO. A 1.6-dB difference was observed between the best
(Beam only) and poorest (Beam + ADRO) options. Among the Zoom options, Zoom only
and Zoom + ADRO were significantly poorer than Zoom + ASC. A 2.2-dB difference
was observed between the best (Zoom + ASC) and poorest (Zoom only) options. The
comparison between Beam and Zoom options showed one significant difference, with
Zoom only significantly poorer than Beam only. No significant difference was
found between the other Beam and Zoom options (Beam + ASC vs Zoom + ASC, Beam +
ADRO vs Zoom + ADRO, and Beam + ASC + ADRO vs Zoom + ASC + ADRO). The best
processing option varied across subjects, with an almost equal number of
participants performing best with a Beam option (n = 15) compared with a Zoom
option (n = 17). There were no significant demographic or audiological moderating
variables for any option. CONCLUSIONS: The results showed no significant
differences between adaptive directionality (Beam) and fixed directionality
(Zoom) when ASC was active in the R-Space environment. This finding suggests that
noise-reduction processing is extremely valuable in loud semidiffuse environments
in which the effectiveness of directional filtering might be diminished. However,
there was no significant difference between the Beam-only and Beam + ASC options,
which is most likely related to the additional noise cancellation performed by
the Beam option (i.e., two-stage directional filtering and noise cancellation).
In addition, the processing options with ADRO resulted in the poorest
performances. This could be related to how the CI recipients were programmed or
the loud noise level used in this study. The best processing option varied across
subjects, but the majority performed best with directional filtering (Beam or
Zoom) in combination with ASC. Therefore in a loud semidiffuse environment, the
use of either Beam + ASC or Zoom + ASC is recommended.
PMID- 25126686
TI - Survey of audiologists' views on risk of falling assessment in the clinic.
AB - BACKGROUND: Falls are a significant health problem for older adults. With the
projected increase in persons aged 65 yr and older by the year 2050, this
continues to be a growing concern. Risk of falling (RoF) assessment is a
multifactorial approach. Audiologists routinely evaluate older patients in the
clinic and therefore might be in an ideal position to identify falling risk
factors. PURPOSE: The purpose of this study was to gain a better understanding of
audiologists' views on RoF assessment related to training and education,
screening and assessment, prevention and intervention, the effectiveness of RoF
assessment, and challenges associated with RoF assessment in the audiology
clinic. RESEARCH DESIGN: The survey was e-mailed to 2000 randomly selected
audiologists across the United States. The survey was designed with the primary
objective of understanding personal views regarding RoF assessment. Demographic
information was included to better understand the type of clinic setting, the
primary age of patients, year of graduation, and highest degree earned.
Additionally, open-ended questions were offered to provide a forum for further
testimonials on current RoF experiences and needs. Questions pertaining to
resources used to assess RoF and counsel patients on RoF were asked to determine
the audiologists' understanding of a multifactorial approach to assessing
patients for RoF. Lastly, a series of Likert scale questions were developed to
indicate the strength of agreement or disagreement pertaining to general
statements about RoF assessment and the challenges associated with an RoF
assessment program. Descriptive statistics (means, standard deviations,
frequencies, and percentages) were used for quantitative survey responses.
Validation of qualitative data was completed by using triangulation sources.
RESULTS: A total of 275 of 2000 audiologists returned the survey; of those who
responded, 238 audiologists were analyzed. Two themes emerged from the survey
responses: resources used to assess RoF and audiologists' personal views on RoF.
Although a majority (83.0% [n = 197/238]) of audiologists surveyed indicated
working with geriatric patients (>=61 yr of age), more than half (62.1% [n =
147/238]) of audiologists surveyed indicated no experience with RoF assessment.
Overall, 75% (n = 175/233) of the surveyed audiologists consider RoF assessment a
role in the audiologist's scope of practice; however, only 16.3% (n = 38/233)
believe audiologists are knowledgeable, 11.8% (n = 27/228) believe audiologists
are sufficiently trained to provide RoF assessment, and 14% (n = 33/238) are
currently implementing RoF as part of vestibular and balance assessment.
CONCLUSIONS: Although audiologists support RoF assessment, further education is
warranted for audiologists to efficiently assess RoF. Many audiologists do not
have the resources or time to administer RoF assessment in their clinics;
however, if audiologists can ask just a few questions regarding fall history and
better understand the risk factors, they can be in a position to refer their
patients to other professionals for further investigation.
PMID- 25126687
TI - Overview of nine computerized, home-based auditory-training programs for adult
cochlear implant recipients.
AB - BACKGROUND: Computerized, home-based auditory-training programs could be
attractive to cochlear implant (CI) recipients who cannot obtain direct intensive
training services and also to busy clinicians who would like to enable CI
recipients to benefit from these programs. However, it is difficult for either
group to know which of the many programs available might best suit individual
needs. PURPOSE: Selecting a computerized home-based program can be challenging
because each offers different features. This article provides an overview of
currently available programs to help clinicians and recipients choose one that is
most suitable. DATA COLLECTION AND ANALYSIS: A narrative literature review and an
advanced Google search of Web sites linked to auditory-training programs were
conducted. This overview builds on and updates information from previous
literature. RESULTS: Nine computerized, home-based auditory-training programs
were identified for overview. Twenty-nine information items and features for each
of the nine programs are presented, categorized by general product and purchase
information, design features of the training paradigm, and auditory and
communication targets. CONCLUSIONS: This article provides a descriptive overview
of computerized, home-based auditory-training programs for the use of clinicians,
CI recipients, researchers, and hearing aid users.
PMID- 25126688
TI - Comment regarding Hannula et al, 2011.
PMID- 25126689
TI - Response to Dobie.
PMID- 25126691
TI - Relationship between conductive hearing loss and maxillary constriction.
AB - OBJECTIVE: To evaluate the relationship between conductive hearing loss and
maxillary constriction. METHOD: A total of 120 people, aged from 7 to 40 years,
who were referred to an audiologist when taking out health insurance or for
school pre-registration check-up, were selected for this study. A total of 60
participants who had hearing threshold levels greater than 15 dB in both ears
were chosen as the conductive hearing loss group. The remaining 60, with normal
hearing thresholds of less than 15 dB, were used as the control group. All
participants were referred to an orthodontic clinic. Participants who had a
posterior crossbite and high palatal vault were considered to suffer from
maxillary constriction. RESULTS: There were no significant differences between
the sex ratios and mean ages of the groups. However, participants with conductive
hearing loss were 3.5 times more likely than controls to suffer from maxillary
constriction. CONCLUSION: Patients who suffer from conductive hearing loss are
likely to show a maxillary abnormality when examined by an orthodontist.
PMID- 25126692
TI - Prevalence of altered passive eruption in orthodontically treated and untreated
patients.
AB - BACKGROUND: Some authors have reported that after orthodontic treatment (OT), a
"gummy smile" might develop. Nevertheless, there are no studies in the literature
that investigate whether OT increases the presence of altered passive eruption
(APE). The primary aim of this cross-sectional study is to evaluate the
prevalence of APE after OT (OT group) and compare it with patients who never
received OT (control group). A secondary aim is to identify which variables are
related to APE. METHODS: The study population consisted of 190 patients (95
patients each in the control and OT groups), providing 1,140 anterior teeth for
the clinical examination. The following clinical parameters were assessed:
presence or absence of APE, clinical crown length, and gingival biotype, which
was divided into three categories: thin-scalloped, thick-flat, and thick
scalloped. RESULTS: Twenty-eight patients (29.5%) were diagnosed with APE in the
control group and 40 (42.1%) in the OT group, although this difference was not
statistically significant (P = 0.07). Furthermore, 34 (75.6%) patients with thick
flat biotype were diagnosed with APE, whereas 30 (31.3%) and four (8.2%) with
thick-scalloped and thin-scalloped biotypes, respectively, had APE. These
differences were statistically significant (P <0.001). CONCLUSIONS: It was
concluded that: 1) the prevalence of APE is higher after OT but not to a
statistically significant degree and 2) APE is more common in individuals with a
thick-flat gingival biotype.
PMID- 25126693
TI - Glycated albumin and calprotectin levels in gingival crevicular fluid from
patients with periodontitis and type 2 diabetes.
AB - BACKGROUND: Patients with diabetes mellitus (DM) have a high prevalence of
periodontitis. Periodontitis in these patients is characterized by severe
inflammation and tissue breakdown, and its diagnosis is important for cures of
periodontitis and DM. The purpose of this study is to investigate the levels of
glycated albumin (GA), a DM marker, and calprotectin, an inflammatory marker, in
gingival crevicular fluid (GCF) from patients with periodontitis and DM (DM-P).
METHODS: The 78 participants in this study were patients with DM, chronic
periodontitis (CP), DM-P, and healthy individuals (H). GCF and blood were
collected, and GA and calprotectin in GCF were analyzed using Western blotting
and enzyme-linked immunosorbent assay. Levels were compared among H, DM, CP, and
DM-P groups. Blood GA and glycated hemoglobin (HbA1c) were measured, and the
correlation among GCF GA and blood HbA1c or GA levels was investigated. Receiver
operating characteristic (ROC) analysis for GCF GA to predict DM was performed.
RESULTS: GA was identified in GCF, and its amount/concentration in GCF samples
from DM and DM-P were significantly higher than those of non-DM groups (H and
CP). Calprotectin amounts in GCF from CP and DM-P were significantly higher than
in H and DM groups. GCF GA level was positively correlated with blood HbA1c and
GA level. ROC analysis of GCF GA showed an optimal cutoff value to predict DM.
CONCLUSIONS: GA showed a high level in GCF from patients with DM. Examination of
GA and calprotectin in GCF may be useful for predicting DM-P.
PMID- 25126695
TI - Stress Reactivity in Insomnia.
AB - This study examined whether individuals with primary insomnia (PI) are more
reactive to stress than good sleepers (GS). PI and GS (n = 20 per group), matched
on gender and age, completed three nights of polysomnography. On the stress
night, participants received a mild electric shock and were told they could
receive additional shocks during the night. Saliva samples were obtained for
analysis of cortisol and alpha amylase along with self-report and visual analog
scales (VAS). There was very little evidence of increased stress on the stress
night, compared to the baseline night. There was also no evidence of greater
stress reactivity in the PI group for any sleep or for salivary measures. In the
GS group, stress reactivity measured by VAS scales was positively associated with
an increase in sleep latency in the experimental night on exploratory analyses.
Individuals with PI did not show greater stress reactivity compared to GS.
PMID- 25126696
TI - Carotid artery dissection associated with an elongated hyoid bone.
AB - A 36-year-old man presented with acute cerebral infarction in the right frontal
lobe associated with right internal carotid artery dissection (CAD). Enhanced
computed tomography revealed right greater horn of the hyoid bone in close
proximity to the right internal carotid artery (ICA). It was speculated that
mechanical compression of the internal carotid artery by the hyoid bone induced
by neck rotation was related to ICA dissection. Greater knowledge of the
association between the hyoid bone and the CAD will lead to increased awareness
and appropriate diagnosis.
PMID- 25126694
TI - Ebselen inhibits hepatitis C virus NS3 helicase binding to nucleic acid and
prevents viral replication.
AB - The hepatitis C virus (HCV) nonstructural protein 3 (NS3) is both a protease,
which cleaves viral and host proteins, and a helicase that separates nucleic acid
strands, using ATP hydrolysis to fuel the reaction. Many antiviral drugs, and
compounds in clinical trials, target the NS3 protease, but few helicase
inhibitors that function as antivirals have been reported. This study focuses on
the analysis of the mechanism by which ebselen (2-phenyl-1,2-benzisoselenazol-3
one), a compound previously shown to be a HCV antiviral agent, inhibits the NS3
helicase. Ebselen inhibited the abilities of NS3 to unwind nucleic acids, to bind
nucleic acids, and to hydrolyze ATP, and about 1 MUM ebselen was sufficient to
inhibit each of these activities by 50%. However, ebselen had no effect on the
activity of the NS3 protease, even at 100 times higher ebselen concentrations. At
concentrations below 10 MUM, the ability of ebselen to inhibit HCV helicase was
reversible, but prolonged incubation of HCV helicase with higher ebselen
concentrations led to irreversible inhibition and the formation of covalent
adducts between ebselen and all 14 cysteines present in HCV helicase. Ebselen
analogues with sulfur replacing the selenium were just as potent HCV helicase
inhibitors as ebselen, but the length of the linker between the phenyl and
benzisoselenazol rings was critical. Modifications of the phenyl ring also
affected compound potency over 30-fold, and ebselen was a far more potent
helicase inhibitor than other, structurally unrelated, thiol-modifying agents.
Ebselen analogues were also more effective antiviral agents, and they were less
toxic to hepatocytes than ebselen. Although the above structure-activity
relationship studies suggest that ebselen targets a specific site on NS3, we were
unable to confirm binding to either the NS3 ATP binding site or nucleic acid
binding cleft by examining the effects of ebselen on NS3 proteins lacking key
cysteines.
PMID- 25126698
TI - Diagnostic accuracy and risk factors of the different lacunar syndromes.
AB - BACKGROUND: The lacunar syndrome is characterized by pure motor, pure sensory, or
sensorimotor hemisymptoms without cortical deficits. It may be less predictable
for a lacunar infarct (LI) than previously believed. The aims of the present
study were to evaluate the diagnostic accuracy of the different lacunar syndromes
and investigate factors associated with acute LI on diffusion-weighted imaging
(DWI). METHODS: Consecutive patients presenting with an acute lacunar syndrome
who were admitted to the stroke unit were enrolled. The patients were examined
clinically and underwent magnetic resonance imaging. The sensitivity and
specificity of the different lacunar syndromes were assessed using DWI as
reference test, and we estimated positive and negative predictive values.
Patients were divided into a LI group and a group without LI. Between-group
differences were analyzed by chi(2) test, t test, and Mann-Whitney U test, as
appropriate. Logistic regression was performed to analyze predictors of LI.
Candidate variables were pure motor syndrome, age, gender, hypertension,
precerebral or intracerebral stenosis, atrial fibrillation, diabetes, coronary
heart disease, and smoking. RESULTS: Eighty-six patients with lacunar syndrome
underwent DWI. The positive predictive value of the lacunar syndrome was 65.1%
and 75% for the pure motor syndrome. Of the candidate variables, only pure motor
syndrome and male gender had significant associations with LI on imaging.
CONCLUSIONS: The clinical diagnosis of patients with lacunar syndromes is
inaccurate, especially among patients with sensorimotor syndrome. DWI is
mandatory for obtaining an accurate diagnosis of the infarct.
PMID- 25126697
TI - Recurrence in intracranial atherosclerotic disease: a stenosis-based analysis.
AB - BACKGROUND: Intracranial atherosclerotic disease is a common cause of stroke; its
incidence and prevalence vary widely by ethnicity. The aim of our study was to
analyze the recurrence rate of cerebrovascular events in patients with
symptomatic and asymptomatic intracranial stenosis (IS). METHODS: We conducted a
historical cohort study including all patients admitted in our hospital for
stroke or transient ischemic attack (TIA) during 2011 and 2012 with information
on intracranial circulation (ultrasonography and/or computed tomography
angiography). We identified patients with symptomatic and asymptomatic IS and
studied the recurrence of cerebrovascular events (TIA or ischemic stroke within
the territory of the stenosis) for a minimum follow-up period of 6 months after
the diagnosis of IS. For the recurrence rate estimation, patients with other
potentially embolic diseases (in cervical arteries or heart) were excluded. We
calculated the rate of recurrence of cerebrovascular events and performed Kaplan
Meier survival curves for symptomatic and asymptomatic IS. RESULTS: We
investigated 1302 patients, mean age was 72.41 years (standard deviation 12.75).
We identified 218 IS in 158 patients, 77 were symptomatic and 141 were
asymptomatic. The recurrence rate of cerebrovascular events was 12.32 per 100
patient-years, with a mean time to recurrence of 1.73 months for symptomatic
intracranial stenosis (SIS) and .88 per 100 patient-years for asymptomatic IS (P
< .001). CONCLUSIONS: These results indicate a high risk of early recurrence of
stroke in the territory of a SIS, highlighting the importance of its early
diagnosis and aggressive treatment.
PMID- 25126699
TI - Fatal intracranial hemorrhage after intravenous thrombolytic therapy for acute
ischemic stroke associated with cancer-related nonbacterial thrombotic
endocarditis.
AB - Nonbacterial thrombotic endocarditis (NBTE) is associated with hypercoagulability
in patients with inflammatory states such as cancer and autoimmune diseases.
Cardiac vegetations caused by NBTE often lead to life-threatening systemic
thromboembolism that most frequently affects the brain, spleen, and kidneys. A 54
year-old woman diagnosed with ovarian cancer suddenly developed back pain and
left hemiparesis. Although intravenous alteplase (rt-PA) therapy was administered
to treat hyperacute ischemic infarction detected by magnetic resonance imaging,
intracranial hemorrhage occurred in the left hemisphere several hours later as
the patient started to lose consciousness. Transthoracic echocardiography then
detected aseptic vegetations on the mitral and aortic valves, indicating NBTE
associated with ovarian cancer. Because therapies for NBTE are limited to
heparinization and control of underlying diseases, thrombolytic therapy for acute
embolic stroke in NBTE has not yet been validated. We postulated that
thrombolytic therapy for cancer-related NBTE might easily cause hemorrhagic
complications because cancer-related NBTE is often similar to the state of
disseminated intravascular coagulation.
PMID- 25126700
TI - Screening of the GPX3 gene identifies the "T" allele of the SNP -861A/T as a risk
for ischemic stroke in young Asian Indians.
AB - BACKGROUND: Deficiency of plasma glutathione peroxidase (GPx-3) has been
associated with platelet-dependent thrombosis. Single-nucleotide polymorphisms
(SNPs) in the promoter region of GPX3 gene have been found associated with the
risk for ischemic stroke in Caucasian populations. The aim of our present study
was to evaluate the impact of genetic variations in the GPX3 gene and plasma GPx
3 antigen levels on ischemic stroke in young Asian Indians. METHODS: One hundred
patients with ischemic stroke and 200 age- and sex-matched controls were studied.
Genetic analysis for the study population was done by a combination of variant
screening using single-stranded conformation polymorphism and final genotyping by
polymerase chain reaction-restriction fragment length polymorphism and allele
specific polymerase chain reactions. Plasma GPx-3 antigen levels were evaluated
using commercial kits. Data were analyzed using genetic analysis software and
statistical tools. RESULTS: Significantly higher GPx-3 levels were observed in
controls compared with patients (controls 26.37 +/- 3.66 MUg/mL and patients
22.83 +/- 4.57 MUg/mL, P < .001). Only the SNP -861A/T was found associated with
stroke phenotype (P < .0001). The SNP -568T/C was observed to significantly
influence plasma GPx-3 levels (P < .05). The haplotype carrying the risk "T"
allele of SNP -861A/T was significantly over-represented in patients with stroke
(P < .0001). CONCLUSIONS: The T allele of -861A/T is a risk allele for the
ischemic stroke phenotype. The -861A/T and -568T/C SNPs may show a statistically
significant association with both plasma GPx-3 antigen levels and the stroke
phenotype in a larger sample size.
PMID- 25126701
TI - Relevance of Health Knowledge in Reporting Maternal Health Complications and Use
of Maternal Health Care in India.
AB - We measured levels of women's health knowledge and their association with the
reporting of maternal health complications and related health care use. We found
that women with higher levels of health knowledge reported more pregnancy and
postnatal complications, and used more maternal health care services. Education
has a positive impact on health, but education alone is not enough to ensure
recognizing and reporting of health complications and increasing the demand for
maternal health care services. We conclude that the provision of health education
for women will help them to identify maternal health complications and improve
their reporting and related health care use.
PMID- 25126702
TI - Anesthesia complications as a childbirth patient safety indicator.
AB - BACKGROUND: The Agency for Healthcare Research and Quality (AHRQ) has established
multiple sets of indicators for quality monitoring and improvement. One such set
is the patient safety indicators (PSIs), which focuses on potentially preventable
hospital complications after surgeries, procedures, and childbirth. Our objective
in this study was to determine the prevalence of childbirth-related anesthesia
complications by method of delivery and to evaluate the variation in complication
rates across hospitals using the AHRQ PSI methodology and a modification specific
to childbirth with the goal of determining the relevance of tracking anesthesia
complications as a potential PSI for childbirth. METHODS: The technical
specifications of the experimental Anesthesia Complication Quality Indicator, one
of the PSI defined by AHRQ, were modified to create a childbirth-specific
indicator that included all childbirth admissions (vaginal and cesarean
deliveries) and complications from general and neuraxial anesthesia/analgesia.
Using California hospital discharge data, we calculated hospital-specific rates,
adjusting for age, race/ethnicity, and pregnancy complications. RESULTS: A total
of 508,842 deliveries occurred in 254 hospitals in California in 2009. Hospitals
with <200 annual deliveries (N = 12) were excluded from analyses. Among 242
hospitals, the rate of anesthesia complications was 0.13% for the standard AHRQ
study population (adult surgical admissions, which included cesarean deliveries).
The childbirth-specific rate of anesthesia complications was 0.31%. When
stratified by method of delivery, complication rates were 0.49% for cesarean
delivery and 0.22% for vaginal delivery (P < 0.0001). The unadjusted mean (SD)
was 0.34% (0.34%), with range (0%-2.46%). The rates of 13 hospitals (including
their 95% confidence limits) remained in the upper quartile as outliers, with
adjusted rates from 0.52% to 2.13%. CONCLUSIONS: Rates of childbirth-related
anesthesia complications may provide an opportunity to identify hospitals with
extreme rates that may provide insights into systematic ways to improve patient
safety.
PMID- 25126703
TI - Glycogen synthase kinase-3beta inhibition prevents remifentanil-induced
postoperative hyperalgesia via regulating the expression and function of AMPA
receptors.
AB - BACKGROUND: Many studies have confirmed that brief remifentanil exposure can
enhance pain sensitivity. We previously reported that activation of glycogen
synthase kinase-3beta (GSK-3beta) contributes to remifentanil-induced
hyperalgesia via regulating N-methyl-D-aspartate receptor plasticity in the
spinal dorsal horn. In this study, we demonstrated that GSK-3beta inhibition
prevented remifentanil-induced postoperative hyperalgesia via regulating alpha
amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) expression
and function in the spinal dorsal horn. METHODS: Using a rat model of
remifentanil-induced incision hyperalgesia, mechanical and thermal pain was
tested 1 day before infusion and 2 hours, 6 hours, 1 day, 2 days, 3 days, 5 days,
and 7 days after infusion. Western blot analysis was used to detect AMPAR subunit
(GluR1 and GluR2) trafficking, AMPAR phosphorylation status, and GSK-3beta
activity in the spinal dorsal horn. Furthermore, whole-cell patch-clamp recording
was used to analyze the effect of GSK-3beta inhibition on AMPAR-induced current
in the spinal dorsal horn. RESULTS: Membrane AMPAR subunit GluR1 was upregulated
in the spinal cord in remifentanil-induced postoperative hyperalgesia rats (275
+/- 36.54 [mean +/- SD] vs 100 +/- 9.53, P = 0.0009). Selective GSK-3beta
inhibitors, LiCl and TDZD, treatment ameliorates remifentanil-induced
postoperative hyperalgesia, and this was associated with the downregulated GluR1
subunit in the membrane fraction (254 +/- 23.51 vs 119 +/- 14.74, P = 0.0027; 254
+/- 23.51 vs 124 +/- 9.35, P = 0.0032). Moreover, remifentanil incubation
increased the amplitude and the frequency of AMPAR-induced current in dorsal horn
neurons (61.09 +/- 9.34 pA vs 32.56 +/- 6.44 pA, P = 0.0009; 118.32 +/- 20.33
milliseconds vs 643.67 +/- 43.29 milliseconds, P = 0.0002), which was prevented
with the application of LiCl and TDZD, respectively. Remifentanil-induced
postoperative pain induced an increase in pGluR1 Ser845 and Rab5, which was
prevented with the application of LiCl and TDZD. CONCLUSIONS: These results
indicate that amelioration of remifentanil-induced postoperative hyperalgesia by
GSK-3beta inhibition is attributed to downregulated AMPAR GluR1 expression in the
membrane fraction and inhibition of AMPAR function via altering pGluR1 and Rab5
expression in the spinal dorsal horn.
PMID- 25126704
TI - What epidural opioid results in the best analgesia outcomes and fewest side
effects after surgery?: a meta-analysis of randomized controlled trials.
AB - BACKGROUND: Epidural opioids are widely used for central neuraxial blockade and
postoperative analgesia. However, differences in analgesic efficacy and side
effect rates among individual opioids remain controversial. METHODS: We conducted
a random-effects meta-analysis of randomized controlled trials that compared at
least 2 continuous epidural infusions for acute postoperative analgesia over at
least 24 hours. Individual study data were weighted by the inverse-variance
method. Visual analog scale (VAS) pain scores were the primary outcome. Secondary
outcomes included opioid side effects, such as pruritus, postoperative nausea and
vomiting (PONV), sedation, hypotension, and respiratory depression. RESULTS:
Nineteen of the 24 trials included compared 2 of the following opioids: morphine,
fentanyl, or sufentanil. The total subjects studied were 1513. Pooled analysis by
type of surgery showed no clinically significant differences in VAS pain scores
at any time after surgery. There were more PONV (OR = 1.91; 95% CI, 1.14-3.18; P
= 0.014) and perhaps pruritus (OR = 1.64; 95% CI, 0.98-2.76; P = 0.162) with
morphine compared to fentanyl. Total opioid consumption differed only in the
trials comparing morphine and fentanyl, where patients in the morphine group
required 1.2 mg (of morphine equivalent) less (95% CI, 0.27-2.18). Use of
analgesic adjuncts was similar for all but 2 studies. CONCLUSIONS: Analgesic
outcome, in terms of VAS pain score, was similar between the epidural opioids
studied. These similarities in analgesia may reflect the common practices of
concurrently using epidural local anesthetics with the opioids and titrating
infusion rates according to a patient's pain status. With respect to side
effects, the incidence of PONV and possibly pruritus was higher with morphine
compared with fentanyl, despite there being similar total opioid consumption
between those groups.
PMID- 25126705
TI - Hypersensitivity reactions to intravenous lipid emulsion in swine: relevance for
lipid resuscitation studies.
AB - BACKGROUND: Reports in the recent experimental literature have provided
contradicting results in different animal species regarding the efficacy of IV
lipid emulsion (ILE) in the reversal of cardiovascular and central nervous system
symptoms of local anesthetic and other lipophilic drug overdoses. In particular,
ILE seemed to be effective in rats, rabbits, dogs, and humans, but not in swine,
for which it not only failed to reverse the adverse effects of anesthetics, but
the animals also developed a generalized cutaneous mottling or a dusky appearance
immediately after ILE, suggestive of another type of toxicity. The latter
symptoms arise in complement (C) activation-related pseudoallergy, a
hypersensitivity reaction to particulate drugs and agents. METHODS: Ten Yorkshire
swine (15-20 kg) were sedated with ketamine and anesthetized with isoflurane. ILE
1.5 and 5 mL/kg 20% was administered via the ear vein while pulmonary arterial
pressure, systemic arterial blood pressure, electrocardiogram, and end-tidal CO2
were recorded continuously. Thromboxane was measured in blood collected at
baseline and 2 and 10 minutes after injections. Complement activation by lipid
emulsion was also assessed in vitro with soluble terminal complement complex
(SC5b-9) and sheep red blood cell assays. RESULTS: Significant increases were
observed in the pulmonary pressure (median [interquartile range]) within minutes
after the administration of ILE, both at doses 1.5 and 5 mL/kg (15 [12-16.5] to
18.5 [16-20] mm Hg, P = 0.0058 and 15.5 [13-17.25] to 39.5 [30.5-48.5],
respectively). The systemic arterial blood pressure increased, and the heart rate
decreased after both injections. Thromboxane B2 concentration (median
[interquartile range]) in the blood plasma increased from a baseline of 617.3
[412.4-920] to 1132 [597.9-1417] pg/mL (P = 0.0055) and from 1276 [1200-2581] to
4046 [2946-8442] pg/mL (P = 0.0017) after the administration of 1.5 and 5 mL/kg
ILE, respectively. Intralipid did not cause in vitro complement activation in
human serum. CONCLUSIONS: ILE causes clinically significant hemodynamic changes
in pigs, in concert with significant increases in the plasma thromboxane
concentration. However, the in vitro tests did not confirm involvement of the
complement system in human sera, leaving the underlying mechanism of these
findings in doubt. Nonetheless, the observed hemodynamic and biochemical effects
of ILE serve as a caveat that the pig is not an ideal model for the study of
interventions involving ILE.
PMID- 25126706
TI - Hybrid nanoparticles by step-growth Sonogashira coupling in disperse systems.
AB - Organic/inorganic hybrid nanoparticles were prepared by a Sonogashira
miniemulsion polymerization of dibromo aryl and diethynyl aryl monomers and
modified titanium dioxide and cadmium selenide nanocrystals, respectively. The
poly(arylene ethynylene) microstructure and polymerization rates, as reflected by
monomer reactivity, decisively impact whether inorganic guest particles can be
trapped to afford a uniform distribution within a newly formed polymer particle
or phase separate. This issue was found to be more critical for the TiO2 rods
studied here. To this end, the compatibility of the organic and inorganic
portions could be improved substantially by the incorporation of functional
groups that bind the inorganic surface to the polymer via an appropriate
termonomer. This concept, in combination with rapid particle formation via a
postpolymerization dispersion of a premade poly(arylene ethynylene)/TiO2
composite as an alternative technique, yielded composite particles with a high
loading of the inorganic nanoparticles.
PMID- 25126708
TI - Role of atrial natriuretic Peptide in oxytocin induced cardioprotection.
AB - BACKGROUND: The purpose of this study was to determine whether endogenous atrial
natriuretic peptide (ANP) contributes to the protective effect of
neurohypophysial hormone oxytocin (OT) in heart preconditioning. METHODS: Sprague
Dawley male rats were subjected to 25 min regional ischaemia and 120 min
reperfusion and were divided into eight groups. Oxytocin or an equivalent volume
of saline was administrated intraperitoneally, 30 min before ischaemia. The OT
receptor antagonist (atosiban), ANP receptor antagonist (anantin) and nitric
oxide synthase inhibitor (L-NAME) were injected 10 min before OT. In other
groups, atosiban, anantin and L-NAME were only administered 40 min prior to
ischaemia. RESULTS: Compared with the ischaemia/reperfusion group (I/R),
alterations in infarct size, biochemical parameters [LDH (lactate dehydrogenase),
CK-MB (creatine kinase-MB), MDA (malondialdehyde) plasma levels] and severity of
ventricular arrhythmia due to I/R injury were attenuated and VF was abolished by
OT treatment. These OT effects were eliminated by OT and ANP receptor blockers
and nitric oxide synthase inhibitor, but anantin did not reverse the effect of OT
in lipid peroxidation. CONCLUSIONS: These findings demonstrate an important
contributory role of ANP in the OT induced protection in myocardial ischaemia
reperfusion. OT also reduced lipid peroxidation with a NO-dependent mechanism.
PMID- 25126707
TI - Metabolic phenotyping reveals a lipid mediator response to ionizing radiation.
AB - Exposure to ionizing radiation has dramatically increased in modern society,
raising serious health concerns. The molecular response to ionizing radiation,
however, is still not completely understood. Here, we screened mouse serum for
metabolic alterations following an acute exposure to gamma radiation using a
multiplatform mass-spectrometry-based strategy. A global, molecular profiling
revealed that mouse serum undergoes a series of significant molecular alterations
following radiation exposure. We identified and quantified bioactive metabolites
belonging to key biochemical pathways and low-abundance, oxygenated,
polyunsaturated fatty acids (PUFAs) in the two groups of animals. Exposure to
gamma radiation induced a significant increase in the serum levels of ether
phosphatidylcholines (PCs) while decreasing the levels of diacyl PCs carrying
PUFAs. In exposed mice, levels of pro-inflammatory, oxygenated metabolites of
arachidonic acid increased, whereas levels of anti-inflammatory metabolites of
omega-3 PUFAs decreased. Our results indicate a specific serum lipidomic
biosignature that could be utilized as an indicator of radiation exposure and as
novel target for therapeutic intervention. Monitoring such a molecular response
to radiation exposure might have implications not only for radiation pathology
but also for countermeasures and personalized medicine.
PMID- 25126709
TI - [Myxoid/round cell liposarcoma of the brachial plexus].
AB - Myxoid/round cell liposarcoma is a soft tissue sarcoma that is extremely rare in
the brachial plexus. We report a case of a myxoid/round cell liposarcoma
originating in the brachial plexus that was surgically resected and evolved well,
with no deficit or recurrence after 2 years of follow-up. To date, there has been
no other case of this sarcoma in the literature.
PMID- 25126710
TI - [Endovascular versus surgical treatment in subarachnoid haemorrhage: Cost
analysis].
AB - OBJECTIVES: To analyse costs of endovascular versus surgical treatment in 80
patients with aneurysmal subarachnoid haemorrhage (aSAH). MATERIAL AND METHODS:
We analysed data on 80 consecutive patients with aSAH between January 2010 and
June 2011. Endovascular treatment was used in 57 patients and surgical in 23
patients. Demographic (gender and age) and clinical data (Hunt-Hess and Fisher
scales), length of stay (ICU and ward) and results at 6 months (Glasgow outcome
scale,[GOS]) were collected. Costs including stay, follow-up, complications and
retreatments were calculated. RESULTS: Age was higher in the endovascular group
(statistically significant). There were no differences between the 2 groups in
Hunt-Hess and Fisher scales. Results at 6 months were also similar, although
slightly better in the surgical group. Length of stay was longer in surgical
patients, both in ICU (mean 1.4 days) and ward (1.7 days). Hospitalisation length
was also related to age and Hunt-Hess and Fisher scales. Costs from embolisation
devices, follow-up and retreatment (12% in this series) made final endovascular
treatment 4.1% more expensive than surgical treatment (?35,835 versus ?34,404).
Endovascular procedure (including retreatments) was 110% more expensive than
surgical treatment (?8,015 versus ?3,817). CONCLUSIONS: There are no differences
between the 2 treatments in terms of morbidity and mortality. Stability of
surgical treatment was higher than that of endovascular, with better occlusion
and lower retreatment rates. Endovascular treatment is more expensive in ruptured
aneurysms, principally due to embolisation device costs, long-term follow-up and
retreatments, in retreatments, in spite of shorter hospital stay. In incidental
aneurysms, which usually need shorter hospitalisation, differences between the 2
treatments could be even larger.
PMID- 25126711
TI - Detection of parasitic plant suicide germination compounds using a high
throughput Arabidopsis HTL/KAI2 strigolactone perception system.
AB - Strigolactones are terpenoid-based plant hormones that act as communication
signals within a plant, between plants and fungi, and between parasitic plants
and their hosts. Here we show that an active enantiomer form of the strigolactone
GR24, the germination stimulant karrikin, and a number of structurally related
small molecules called cotylimides all bind the HTL/KAI2 alpha/beta hydrolase in
Arabidopsis. Strigolactones and cotylimides also promoted an interaction between
HTL/KAI2 and the F-box protein MAX2 in yeast. Identification of this chemically
dependent protein-protein interaction prompted the development of a yeast-based,
high-throughput chemical screen for potential strigolactone mimics. Of the 40
lead compounds identified, three were found to have in planta strigolactone
activity using Arabidopsis-based assays. More importantly, these three compounds
were all found to stimulate suicide germination of the obligate parasitic plant
Striga hermonthica. These results suggest that screening strategies involving
yeast/Arabidopsis models may be useful in combating parasitic plant infestations.
PMID- 25126712
TI - Catalyst design in oxidation chemistry; from KMnO4 to artificial metalloenzymes.
AB - Oxidation reactions are an important part of the synthetic organic chemist's
toolkit and continued advancements have, in many cases, resulted in high yields
and selectivities. This review aims to give an overview of the current state-of
the-art in oxygenation reactions using both chemical and enzymatic processes, the
design principles applied to date and a possible future in the direction of
hybrid catalysts combining the best of chemical and natural design.
PMID- 25126713
TI - Inhibitory effects of p-alkylaminophenol on melanogenesis.
AB - Melanin protects the skin against ultraviolet (UV) rays. It is produced in excess
by UV radiation, which causes skin disorders and pigmentation. Retinoic acid (RA)
decreases the levels of epidermal melanin by suppressing the expression of
melanogenic enzymes including tyrosinase, which is the rate-limiting enzyme in
melanin synthesis. However, RA shows inflammatory effects on the skin. In an
effort to develop potent inhibitors of melanin synthesis, new aminophenol
derivatives were synthesized based on structure-activity relationship studies of
N-(4-hydroxyphenyl)retinamide (1), a derivative of RA. We investigated the
inhibitory effects of a series of aminophenols on melanogenesis using B16
melanoma cells. p-Decylaminophenol (3) was the most potent agent examined,
showing significant inhibition of B16 tyrosinase activities at concentrations
less than what was required to achieve a similar level of inhibition by the well
known tyrosinase inhibitor, kojic acid. Compound 3 decreased melanin content and
inhibited protein and mRNA expression for the tyrosinase-related protein-1 (TRP
1). It also inhibited the microphthalmia-associated transcription factor (MITF),
a master transcription factor in melanogenesis. Compound 3 suppressed MEK/ERK
signal pathways involved in the activation and expression of MITF. The data
indicate that 3 inhibits TRP-1 expression by decreasing MITF expression through
suppressing MEK/ERK signal pathways. This results in the reduction of melanin in
B16 cells. Compound 3 might be an alternative to RA as a potent inhibitor of
melanogenesis.
PMID- 25126714
TI - Design, stereoselective synthesis, configurational stability and biological
activity of 7-chloro-9-(furan-3-yl)-2,3,3a,4-tetrahydro-1H-benzo[e]pyrrolo[2,1
c][1,2,4]thiadiazine 5,5-dioxide.
AB - Chiral 5-arylbenzothiadiazine derivatives have recently attracted particular
attention because they exhibit an interesting pharmacological activity as AMPA
receptor (AMPAr) positive modulators. However, investigations on their
configurational stability suggest a rapid enantiomerization in physiological
conditions. In order to enhance configurational stability, preserving AMPAr
activity, we have designed the novel compound (R,S)-7-chloro-9-(furan-3-yl)
2,3,3a,4-tetrahydro-1H-benzo[e]pyrrolo[2,1-c][1,2,4]thiadiazine 5,5-dioxide
bearing a pyrrolo moiety coupled with the 5-(furan-3-yl) substituent on
benzothiadiazine core. A stereoselective synthesis was projected to obtain single
enantiomer of the latter compound. Absolute configuration was assigned by X-ray
crystal structure. Patch clamp experiments evaluating the activity of single
enantiomers as AMPAr positive allosteric modulator showed that R stereoisomer is
the active component. Molecular modeling studies were performed to explain
biological results. An on-column stopped-flow bidimensional recycling HPLC
procedure was applied to obtain on a large scale the active enantiomer with
enantiomeric enrichment starting from the racemic mixture of the compound.
PMID- 25126715
TI - Mechanical compression insults induce nanoscale changes of membrane-skeleton
arrangement which could cause apoptosis and necrosis in dorsal root ganglion
neurons.
AB - In a primary spinal cord injury, the amount of mechanical compression insult that
the neurons experience is one of the most critical factors in determining the
extent of the injury. The ultrastructural changes that neurons undergo when
subjected to mechanical compression are largely unknown. In the present study,
using a compression-driven instrument that can simulate mechanical compression
insult, we applied mechanical compression stimulation at 0.3, 0.5, and 0.7 MPa to
dorsal root ganglion (DRG) neurons for 10 min. Combined with atomic force
microscopy, we investigated nanoscale changes in the membrane-skeleton,
cytoskeleton alterations, and apoptosis induced by mechanical compression injury.
The results indicated that mechanical compression injury leads to rearrangement
of the membrane-skeleton compared with the control group. In addition, mechanical
compression stimulation induced apoptosis and necrosis and also changed the
distribution of the cytoskeleton in DRG neurons. Thus, the membrane-skeleton may
play an important role in the response to mechanical insults in DRG neurons.
Moreover, sudden insults caused by high mechanical compression, which is most
likely conducted by the membrane-skeleton, may induce necrosis, apoptosis, and
cytoskeletal alterations.
PMID- 25126718
TI - Trachelorraphy in cases of recurrent second trimester loss and prior failed
vaginal cerclage.
AB - OBJECTIVE: To evaluate the obstetric results of trachelorraphy in the prevention
of recurrent second trimester loss in cases of prior failed vaginal cerclage.
STUDY DESIGN: Data were collected retrospectively and prospectively from medical
records. The analysis examined data for 18 women who underwent trachelorraphy
between 2004 and 2013 at a tertiary referral unit in France. All patients in this
high-risk population had a history of two or more second trimester losses, or one
second trimester loss and one preterm labour, and at least one prior failed
transvaginal cerclage. The main outcome measures were: livebirth rate; rate of
second trimester loss; and surgical complications. RESULTS: Twenty pregnancies
were conceived in 16 patients following trachelorraphy. Three patients
experienced two pregnancies. Among the 20 pregnancies, there was one case of
fetal loss in the first trimester; this pregnancy was excluded from the analysis.
Of the remaining 19 pregnancies, there were nine (47%) term deliveries (after 37
weeks of gestation), seven (32%) preterm deliveries and three (16%) second
trimester losses. The overall fetal survival rate was 84%. Surgical outcomes were
excellent, with no complications. CONCLUSION: Trachelorraphy is a safe,
reproducible, easy-to-learn procedure for the prevention of recurrent second
trimester loss in cases of prior failed vaginal cerclage. The procedure has
encouraging and favourable perinatal outcomes in patients with a poor obstetric
history.
PMID- 25126716
TI - Characterization of long non-coding RNA transcriptome in clear-cell renal cell
carcinoma by next-generation deep sequencing.
AB - INTRODUCTION: Long non-coding RNA (lncRNA) have proven to play key roles in cell
physiology from nuclear organization and epigenetic remodeling to post
transcriptional regulation. Last decade, gene expression based-classifications
have been developed in clear-cell renal cell carcinoma (ccRCC) to identify
distinct subtypes of disease and predict patient's outcome. However, there are no
current lncRNA comprehensive characterizations in ccRCC. PATIENTS AND METHODS:
RNA-sequencing profiles of 475 primary ccRCC samples from the Cancer Genome Atlas
(TCGA) were used to assess expressed lncRNA and identify lncRNA-based
classification. In addition, integrative analysis was performed to correlate
tumor subtypes with copy-number alterations and somatic mutations. RESULTS: Using
stringent criteria, we identified 1934 expressed lncRNA and assessed their
chromatin marks. Unsupervised clustering unravels four lncRNA subclasses in ccRCC
associated with distinct clinicopathological and genomic features of this
disease. Cluster C2 (23.4%) defines the most aggressive tumours, with the highest
Fuhrman grade and stage and the worst overall survival time. Furthermore, cluster
C2 is enriched for 9p deletion and chromatin remodeler BAP1 somatic mutations.
Interestingly, cluster C4 (7.8%) is related to a tumor subtype arising from the
distal tubules of the nephron. Consistent with its distinct ontogeny, cluster C4
is devoid of classical alterations seen in ccRCC, bears frequent 1p deletion and
17q gain, and is enriched for MiTF/TFE translocations. In addition,
reexaminations of copy-number data from one side and tumor histology by
pathologists from the other side reveal misclassified tumors within C4 cluster
including chromophobe RCC and clear cell papillary RCC. CONCLUSION: This study
establishes a foundation for categorizing lncRNA subclasses, which may contribute
to understand tumor ontogeny and help predicting patients' outcome in ccRCC.
PMID- 25126717
TI - The extent of diffusion MRI markers of neuroinflammation and white matter
deterioration in chronic schizophrenia.
AB - In a previous study we have demonstrated, using a novel diffusion MRI analysis
called free-water imaging, that the early stages of schizophrenia are more likely
associated with a neuroinflammatory response and less so with a white matter
deterioration or a demyelination process. What is not known is how
neuroinflammation and white matter deterioration change along the progression of
the disorder. In this study we apply the free-water measures on a population of
29 chronic schizophrenia subjects and compare them with 25 matching controls. Our
aim was to compare the extent of free-water imaging abnormalities in chronic
subjects with the ones previously obtained for subjects at their first psychotic
episode. We find that chronic subjects showed a limited extent of abnormal
increase in the volume of the extracellular space, suggesting a less extensive
neuroinflammatory response relative to patients at the onset of schizophrenia. At
the same time, the chronic schizophrenia subjects had greater extent of reduced
fractional anisotropy compared to the previous study, suggesting increased white
matter deterioration along the progression of the disease. Our findings
substantiate the role of neuroinflammation in the earlier stages of the disorder,
and the effect of neurodegeneration that is worsening in the chronic phase.
PMID- 25126719
TI - [Neonatal enterovirus infections reported in France in 2012].
AB - Enteroviruses (EVs) are among the most common viruses infecting humans. One-third
of EV infections affect children under 1 year of age. Neonatal EV infections lead
to a wide range of clinical manifestations, from mild febrile illness to severe,
potentially fatal sepsis-like conditions with multiorgan failure. EV detections
by serotype are reported by the National Reference Centre for EV Infections Lyon
on a monthly basis. Demographic, clinical, and biological data were also
collected in neonates hospitalized in 2012 for EV infection. Two subgroups were
identified according to the beginning of symptoms: until 8 days of life (D8) or
strictly after D8. There were 120 neonatal EV infections. Before D8, children
with severe infection were born more prematurely with a low birth weight. The EVs
most commonly detected in neonates were CV-B4 and E-11. Risk factors for severe
EV infections included liver (73% before D8) and hematological damage
(thrombocytopenia, 82%; coagulopathy, 64% before D8). This study suggests that
systematic serotyping of neonatal EV infections and biological monitoring of
liver function could be useful for early identification of children at high risk
of clinical severity and fatality.
PMID- 25126720
TI - Post-appendectomy surgical site infection rate after using an antimicrobial film
incise drape: a prospective study.
AB - BACKGROUND: An appendectomy is a contaminated or potentially dirty surgical
procedure that can be associated with surgical site infection (SSI). METHODS: A
single-center unblinded prospective cohort study examined the role of
antimicrobial incise film drapes in lowering the rate of SSI after appendectomy.
Any patient aged 12 years or older who was scheduled for open appendectomy for
acute appendicitis was included. Patients were assigned to two groups. Group 1
(n=52) had the standard five-minute skin preparation with 10% povidone-iodine
soap followed by the application of an antimicrobial film incise drape, and group
2 (n=39) had the standard skin preparation alone. RESULTS: Six (11.5%) of the 52
patients who had the antimicrobial film incise drape and two (5.1%) of the 39
patients who did not have the drape developed SSI (p=NS). Of the six patients in
the antimicrobial film group with post-operative SSI, three had a perforated
appendix, two had a gangrenous appendix, and one had an inflamed appendix. In
group 2, one patient had an inflamed appendix and the other had a perforated
appendix. The median length of stay in the hospital was two days (range 1-11
days) for both groups. CONCLUSION: Our study did not support the view that
antimicrobial film incise drapes can lower the rate of post-appendectomy SSI.
Moreover, the length of stay was not minimized by the use of these drapes.
PMID- 25126722
TI - The community structure of the global corporate network.
AB - We investigate the community structure of the global ownership network of
transnational corporations. We find a pronounced organization in communities that
cannot be explained by randomness. Despite the global character of this network,
communities reflect first of all the geographical location of firms, while the
industrial sector plays only a marginal role. We also analyze the meta-network in
which the nodes are the communities and the links are obtained by aggregating the
links among firms belonging to pairs of communities. We analyze the network
centrality of the top 50 communities and we provide a quantitative assessment of
the financial sector role in connecting the global economy.
PMID- 25126721
TI - Effects of 28Si ions, 56Fe ions, and protons on the induction of murine acute
myeloid leukemia and hepatocellular carcinoma.
AB - Estimates of cancer risks posed to space-flight crews by exposure to high atomic
number, high-energy (HZE) ions are subject to considerable uncertainty because
epidemiological data do not exist for human populations exposed to similar
radiation qualities. We assessed the carcinogenic effects of 300 MeV/n 28Si or
600 MeV/n 56Fe ions in a mouse model for radiation-induced acute myeloid leukemia
and hepatocellular carcinoma. C3H/HeNCrl mice were irradiated with 0.1, 0.2, 0.4,
or 1 Gy of 300 MeV/n 28Si ions, 600 MeV/n 56Fe ions or 1 or 2 Gy of protons
simulating the 1972 solar particle event (1972SPE) at the NASA Space Radiation
Laboratory. Additional mice were irradiated with 137Cs gamma rays at doses of 1,
2, or 3 Gy. All groups were followed until they were moribund or reached 800 days
of age. We found that 28Si or 56Fe ions do not appear to be substantially more
effective than gamma rays for the induction of acute myeloid leukemia. However,
28Si or 56Fe ion irradiated mice had a much higher incidence of hepatocellular
carcinoma than gamma ray irradiated or proton irradiated mice. These data
demonstrate a clear difference in the effects of these HZE ions on the induction
of leukemia compared to solid tumors, suggesting potentially different mechanisms
of tumorigenesis. Also seen in this study was an increase in metastatic
hepatocellular carcinoma in the 28Si and 56Fe ion irradiated mice compared with
those exposed to gamma rays or 1972SPE protons, a finding with important
implications for setting radiation exposure limits for space-flight crew members.
PMID- 25126723
TI - The BCL2L1 and PGAM5 axis defines hypoxia-induced receptor-mediated mitophagy.
AB - Receptor-mediated mitophagy is one of the major mechanisms of mitochondrial
quality control essential for cell survival. We previously have identified FUNDC1
as a mitophagy receptor for selectively removing damaged mitochondria in
mammalian systems. A critical unanswered question is how receptor-mediated
mitophagy is regulated in response to cellular and environmental cues. Here, we
report the striking finding that BCL2L1/Bcl-xL, but not BCL2, suppresses
mitophagy mediated by FUNDC1 through its BH3 domain. Mechanistically, we
demonstrate that BCL2L1, but not BCL2, interacts with and inhibits PGAM5, a
mitochondrially localized phosphatase, to prevent the dephosphorylation of FUNDC1
at serine 13 (Ser13), which activates hypoxia-induced mitophagy. Our results
showed that the BCL2L1-PGAM5-FUNDC1 axis is critical for receptor-mediated
mitophagy in response to hypoxia and that BCL2L1 possesses unique functions
distinct from BCL2.
PMID- 25126724
TI - MIR125B1 represses the degradation of the PML-RARA oncoprotein by an autophagy
lysosomal pathway in acute promyelocytic leukemia.
AB - Acute promyelocytic leukemia (APL) is characterized by the t(15;17)-associated
PML-RARA fusion gene. We have previously found that MIR125B1 is highly expressed
in patients with APL and may be associated with disease pathogenesis; however,
the mechanism by which MIR125B1 exerts its oncogenic potential has not been fully
elucidated. Here, we demonstrated that MIR125B1 abundance correlates with the PML
RARA status. MIR125B1 overexpression enhanced PML-RARA expression and inhibited
the ATRA-induced degradation of the PML-RARA oncoprotein. RNA-seq analysis
revealed a direct link between the PML-RARA degradation pathway and MIR125B1
arrested differentiation. We further demonstrated that the MIR125B1-mediated
blockade of PML-RARA proteolysis was regulated via an autophagy-lysosomal
pathway, contributing to the inhibition of APL differentiation. Furthermore, we
identified DRAM2 (DNA-damage regulated autophagy modulator 2), a critical
regulator of autophagy, as a novel target that was at least partly responsible
for the function of MIR125B1 involved in autophagy. Importantly, the knockdown
phenotypes for DRAM2 are similar to the effects of overexpressing MIR125B1 as
impairment of PML-RARA degradation, inhibition of autophagy, and myeloid cell
differentiation arrest. These effects of MIR125B1 and its target DRAM2 were
further confirmed in an APL mouse model. Thus, MIR125B1 dysregulation may
interfere with the effectiveness of ATRA-mediated differentiation through an
autophagy-dependent pathway, representing a novel potential APL therapeutic
target.
PMID- 25126725
TI - The nascent polypeptide-associated complex is essential for autophagic flux.
AB - The ribosome-associated nascent polypeptide-associated complex (NAC) is involved
in multiple cotranslational processes, including protein transport into the ER
and mitochondria, and also acts as a chaperone to assist protein folding. Here we
demonstrated that NAC is also essential for autophagic degradation of a variety
of protein aggregates in C. elegans. Loss of function of NAC impairs lysosome
function, resulting in accumulation of autophagic substrates in enlarged
autolysosomes. Knockdown of mammalian NAC also causes accumulation of
nondegradative autolysosomes. Our study revealed that NAC plays an evolutionarily
conserved role in the autophagy pathway and thus in maintaining protein
homeostasis under physiological conditions.
PMID- 25126728
TI - Human GABARAP can restore autophagosome biogenesis in a C. elegans lgg-1 mutant.
AB - We recently described in C. elegans embryos, the acquisition of specialized
functions for orthologs of yeast Atg8 (e.g., mammalian MAP1LC3/LC3) in allophagy,
a selective and developmentally regulated autophagic process. During the
formation of double-membrane autophagosomes, the ubiquitin-like Atg8/LC3 proteins
are recruited to the membrane through a lipidation process. While at least 6
orthologs and paralogs are present in mammals, C. elegans only possesses 2
orthologs, LGG-1 and LGG-2, corresponding to the GABARAP-GABARAPL2/GATE-16 and
the MAP1LC3 families, respectively. During allophagy, LGG-1 acts upstream of LGG
2 and is essential for autophagosome biogenesis, whereas LGG-2 facilitates their
maturation. We demonstrated that LGG-2 directly interacts with the HOPS complex
subunit VPS-39, and mediates the tethering between autophagosomes and lysosomes,
which also requires RAB-7. In the present addendum, we compared the localization
of autophagosomes, endosomes, amphisomes, and lysosomes in vps-39, rab-7, and lgg
2 depleted embryos. Our results suggest that lysosomes interact with
autophagosomes or endosomes through a similar mechanism. We also performed a
functional complementation of an lgg-1 null mutant with human GABARAP, its closer
homolog, and showed that it localizes to autophagosomes and can rescue LGG-1
functions in the early embryo.
PMID- 25126730
TI - Folding into an autophagosome: ATG5 sheds light on how plants do it.
AB - Autophagosomes arise in yeast and animals from the sealing of a cup-shaped double
membrane precursor, the phagophore. The concerted action of about 30
evolutionarily conserved autophagy related (ATG) proteins lies at the core of
this process. However, the mechanisms allowing phagophore generation and its
differentiation into a sealed autophagosome are still not clear in detail, and
very little is known in plants. This is due in part to the scarcity of
structurally informative, real-time imaging data of ATG proteins at the
phagophore site. Among these, the ATG5 complex directs anchoring of ATG8 to the
phagophore, an event required for membrane expansion. Detailed real-time and 3D
imaging of ATG5, ATG8, and an ER marker at the expanding phagophore allowed us to
propose a model for autophagosome formation in plants. This model implies tight
connections of the growing phagophore with the outer face of the cortical
endoplasmic reticulum and prompts new questions on the mechanism of autophagosome
biogenesis.
PMID- 25126729
TI - Berberine attenuates autophagy in adipocytes by targeting BECN1.
AB - The lysosomal degradation pathway, autophagy, is essential for the maintenance of
cellular homeostasis. Recently, autophagy has been demonstrated to be required in
the process of adipocyte conversion. However, its role in mature adipocytes under
physiological and pathological conditions remains unclear. Here, we report a
major function of BECN1 in the regulation of basal autophagy in mature
adipocytes. We also show that berberine, a natural plant alkaloid, inhibits basal
autophagy in adipocytes and adipose tissue of mice fed a high-fat diet via
downregulation of BECN1 expression. We further demonstrate that berberine has a
pronounced effect on the stability of Becn 1 mRNA through the Mir30 family. These
findings explore the potential of BECN1 as a key molecule and a drug target for
regulating autophagy in mature adipocytes.
PMID- 25126726
TI - FLCN, a novel autophagy component, interacts with GABARAP and is regulated by
ULK1 phosphorylation.
AB - Birt-Hogg-Dube (BHD) syndrome is a rare autosomal dominant condition caused by
mutations in the FLCN gene and characterized by benign hair follicle tumors,
pneumothorax, and renal cancer. Folliculin (FLCN), the protein product of the
FLCN gene, is a poorly characterized tumor suppressor protein, currently linked
to multiple cellular pathways. Autophagy maintains cellular homeostasis by
removing damaged organelles and macromolecules. Although the autophagy kinase
ULK1 drives autophagy, the underlying mechanisms are still being unraveled and
few ULK1 substrates have been identified to date. Here, we identify that loss of
FLCN moderately impairs basal autophagic flux, while re-expression of FLCN
rescues autophagy. We reveal that the FLCN complex is regulated by ULK1 and
elucidate 3 novel phosphorylation sites (Ser406, Ser537, and Ser542) within FLCN,
which are induced by ULK1 overexpression. In addition, our findings demonstrate
that FLCN interacts with a second integral component of the autophagy machinery,
GABA(A) receptor-associated protein (GABARAP). The FLCN-GABARAP association is
modulated by the presence of either folliculin-interacting protein (FNIP)-1 or
FNIP2 and further regulated by ULK1. As observed by elevation of GABARAP,
sequestome 1 (SQSTM1) and microtubule-associated protein 1 light chain 3
(MAP1LC3B) in chromophobe and clear cell tumors from a BHD patient, we found that
autophagy is impaired in BHD-associated renal tumors. Consequently, this work
reveals a novel facet of autophagy regulation by ULK1 and substantially
contributes to our understanding of FLCN function by linking it directly to
autophagy through GABARAP and ULK1.
PMID- 25126727
TI - Autophagy in microglia degrades extracellular beta-amyloid fibrils and regulates
the NLRP3 inflammasome.
AB - Accumulation of beta-amyloid (Abeta) and resultant inflammation are critical
pathological features of Alzheimer disease (AD). Microglia, a primary immune cell
in brain, ingests and degrades extracellular Abeta fibrils via the lysosomal
system. Autophagy is a catabolic process that degrades native cellular
components, however, the role of autophagy in Abeta degradation by microglia and
its effects on AD are unknown. Here we demonstrate a novel role for autophagy in
the clearance of extracellular Abeta fibrils by microglia and in the regulation
of the Abeta-induced NLRP3 (NLR family, pyrin domain containing 3) inflammasome
using microglia specific atg7 knockout mice and cell cultures. We found in
microglial cultures that Abeta interacts with MAP1LC3B-II via OPTN/optineurin and
is degraded by an autophagic process mediated by the PRKAA1 pathway. We
anticipate that enhancing microglial autophagy may be a promising new therapeutic
strategy for AD.
PMID- 25126731
TI - Correlative light and electron microscopy imaging of autophagy in a zebrafish
infection model.
AB - High-resolution imaging of autophagy has been used intensively in cell culture
studies, but so far it has been difficult to visualize this process in detail in
whole animal models. In this study we present a versatile method for high
resolution imaging of microbial infection in zebrafish larvae by injecting
pathogens into the tail fin. This allows visualization of autophagic compartments
by light and electron microscopy, which makes it possible to correlate images
acquired by the 2 techniques. Using this method we have studied the autophagy
response against Mycobacterium marinum infection. We show that mycobacteria
during the progress of infection are frequently associated with GFP-Lc3-positive
vesicles, and that 2 types of GFP-Lc3-positive vesicles were observed. The
majority of these vesicles were approximately 1 MUm in size and in close vicinity
of bacteria, and a smaller number of GFP-Lc3-positive vesicles was larger in size
and were observed to contain bacteria. Quantitative data showed that these larger
vesicles occurred significantly more in leukocytes than in other cell types, and
that approximately 70% of these vesicles were positive for a lysosomal marker.
Using electron microscopy, it was found that approximately 5% of intracellular
bacteria were present in autophagic vacuoles and that the remaining intracellular
bacteria were present in phagosomes, lysosomes, free inside the cytoplasm or
occurred as large aggregates. Based on correlation of light and electron
microscopy images, it was shown that GFP-Lc3-positive vesicles displayed
autophagic morphology. This study provides a new approach for injection of
pathogens into the tail fin, which allows combined light and electron microscopy
imaging in vivo and opens new research directions for studying autophagy process
related to infectious diseases.
PMID- 25126732
TI - Autophagy is required for G1/G0 quiescence in response to nitrogen starvation in
Saccharomyces cerevisiae.
AB - In response to starvation, cells undergo increased levels of autophagy and cell
cycle arrest but the role of autophagy in starvation-induced cell cycle arrest is
not fully understood. Here we show that autophagy genes regulate cell cycle
arrest in the budding yeast Saccharomyces cerevisiae during nitrogen starvation.
While exponentially growing wild-type yeasts preferentially arrest in G1/G0 in
response to starvation, yeasts carrying null mutations in autophagy genes show a
significantly higher percentage of cells in G2/M. In these autophagy-deficient
yeast strains, starvation elicits physiological properties associated with
quiescence, such as Snf1 activation, glycogen and trehalose accumulation as well
as heat-shock resistance. However, while nutrient-starved wild-type yeasts finish
the G2/M transition and arrest in G1/G 00 autophagy-deficient yeasts arrest in
telophase. Our results suggest that autophagy is crucial for mitotic exit during
starvation and appropriate entry into a G1/G0 quiescent state.
PMID- 25126735
TI - A mitochondrial-associated link between an effector caspase and autophagic flux.
AB - It has become evident that caspases function in nonapoptotic cellular processes
in addition to the canonical role for caspases in apoptotic cell death. We
recently demonstrated that the Drosophila effector caspase Dcp-1 localizes to the
mitochondria and positively regulates starvation-induced autophagic flux during
mid-oogenesis. Loss of Dcp-1 leads to elongation of the mitochondrial network,
increased levels of the adenine nucleotide translocase sesB, increased ATP
levels, and a reduction in autophagy. We found that sesB is a negative regulator
of autophagic flux, and Dcp-1 interacts with sesB in a nonproteolytic manner to
regulate its stability, uncovering a novel mechanism of mitochondrial associated,
caspase-mediated regulation of autophagy in vivo.
PMID- 25126734
TI - Endoplasmic reticulum stress induced by tunicamycin and thapsigargin protects
against transient ischemic brain injury: Involvement of PARK2-dependent
mitophagy.
AB - Transient cerebral ischemia leads to endoplasmic reticulum (ER) stress. However,
the contributions of ER stress to cerebral ischemia are not clear. To address
this issue, the ER stress activators tunicamycin (TM) and thapsigargin (TG) were
administered to transient middle cerebral artery occluded (tMCAO) mice and oxygen
glucose deprivation-reperfusion (OGD-Rep.)-treated neurons. Both TM and TG showed
significant protection against ischemia-induced brain injury, as revealed by
reduced brain infarct volume and increased glucose uptake rate in ischemic
tissue. In OGD-Rep.-treated neurons, 4-PBA, the ER stress releasing mechanism,
counteracted the neuronal protection of TM and TG, which also supports a
protective role of ER stress in transient brain ischemia. Knocking down the ER
stress sensor Eif2s1, which is further activated by TM and TG, reduced the OGD
Rep.-induced neuronal cell death. In addition, both TM and TG prevented PARK2
loss, promoted its recruitment to mitochondria, and activated mitophagy during
reperfusion after ischemia. The neuroprotection of TM and TG was reversed by
autophagy inhibition (3-methyladenine and Atg7 knockdown) as well as Park2
silencing. The neuroprotection was also diminished in Park2(+/-) mice. Moreover,
Eif2s1 and downstream Atf4 silencing reduced PARK2 expression, impaired mitophagy
induction, and counteracted the neuroprotection. Taken together, the present
investigation demonstrates that the ER stress induced by TM and TG protects
against the transient ischemic brain injury. The PARK2-mediated mitophagy may be
underlying the protection of ER stress. These findings may provide a new strategy
to rescue ischemic brains by inducing mitophagy through ER stress activation.
PMID- 25126736
TI - Autophagy deficiency stabilizes TWIST1 to promote epithelial-mesenchymal
transition.
AB - The transcription factor TWIST1 is a basic helix-loop-helix protein that
regulates epithelial-mesenchymal transition (EMT) in early embryonic
morphogenesis, cancer development, and cancer metastasis. The regulation of
TWIST1 remains poorly understood. Recently, we found that autophagy deficiency
stabilizes TWIST1 protein through SQSTM1/p62 accumulation. SQSTM1 binds with
TWIST1 to inhibit TWIST1 degradation in both autophagosomes and proteasomes.
SQSTM1-mediated TWIST1 stabilization promotes EMT in vitro, and tumor growth and
metastasis in mice. We propose autophagy as a new mechanism to control the TWIST1
protein levels and activity in cancer development and progression.
PMID- 25126737
TI - HMGB1-dependent and -independent autophagy.
AB - HMGB1 (high mobility group box 1) is a multifunctional, ubiquitous protein
located inside and outside cells that plays a critical role in various
physiological and pathological processes including cell development,
differentiation, inflammation, immunity, metastasis, metabolism, and death.
Increasing evidence demonstrates that HMGB1-dependent autophagy promotes
chemotherapy resistance, sustains tumor metabolism requirements and T cell
survival, prevents polyglutamine aggregates and excitotoxicity, and protects
against endotoxemia, bacterial infection, and ischemia-reperfusion injury in
vitro or in vivo. In contrast, HMGB1 may not be required for autophagy in some
organs such as the liver and heart. Understanding HMGB1-dependent and
independent autophagy in more detail will provide insight into the integrated
stress response and guide HMGB1-based therapeutic intervention.
PMID- 25126738
TI - Positive doping results caused by the single-dose local injection of
triamcinolone acetonide.
AB - Triamcinolone acetonide (TA) is classified as an S9 glucocorticoid in the 2014
Prohibited List published by the World Anti-Doping Agency, which caused it to be
prohibited in-competition when administered orally, intravenously,
intramuscularly or rectally. The Minimum Required Performance Level (MRPL) for
the detection and identification of glucocorticoids is 30 ng/mL. Other common
local injection routes, such as intraarticular, intratendinous, or intrabursal
injection, are not prohibited. The purpose of this study was to analyze the TA
and triamcinolone (T) concentrations in urine after a single injection of TA in
patients to determine if it would produce a positive result. This study was
performed on 40 patients with sports injuries or joint pains. TA was administered
locally (doses varied from 12 to 80 mg). Samples were extracted using a solid
phase extraction column, followed by hydrolysis and liquid extraction using
diethyl ether. The elution solvents were collected and dried. The dried residue
was reconstituted and assayed by performing liquid chromatography-tandem mass
spectrometry (LC-MS/MS) in positive ionization mode using electrospray ionization
and multiple-reaction monitoring as the acquisition mode. The results
demonstrated that the concentrations of both TA and T in urine exceeded the MRPL
(30 ng/mL) after a single local injection. We obtained positive results for TA in
25 patients, and a positive result for T in one patient. Furthermore, the
metabolic situation of TA, a long-acting glucocorticoid, was not an exact linear
model. The highest concentrations of TA and T appeared 1-4h after injection. This
information could be useful for limiting the misuse of TA by athletes. We suggest
that athletes be aware when using TA injections during a competition period and
obtain approval for therapeutic use exemption prior to using TA.
PMID- 25126739
TI - Factors affecting human milk composition.
PMID- 25126740
TI - Toll-like receptor 9 mediated responses in cardiac fibroblasts.
AB - Altered cardiac Toll-like receptor 9 (TLR9) signaling is important in several
experimental cardiovascular disorders. These studies have predominantly focused
on cardiac myocytes or the heart as a whole. Cardiac fibroblasts have recently
been attributed increasing significance in mediating inflammatory signaling.
However, putative TLR9-signaling through cardiac fibroblasts remains non
investigated. Thus, our aim was to explore TLR9-signaling in cardiac fibroblasts
and investigate the consequence of such receptor activity on classical cardiac
fibroblast cellular functions. Cultivated murine cardiac fibroblasts were
stimulated with different TLR9 agonists (CpG A, B and C) and assayed for the
secretion of inflammatory cytokines (tumor necrosis factor alpha [TNFalpha],
CXCL2 and interferon alpha/beta). Expression of functional cardiac fibroblast
TLR9 was proven as stimulation with CpG B and -C caused significant CXCL2 and
TNFalpha-release. These responses were TLR9-specific as complete inhibition of
receptor-stimulated responses was achieved by co-treatment with a TLR9-antagonist
(ODN 2088) or chloroquine diphosphate. TLR9-stimulated responses were also found
more potent in cardiac fibroblasts when compared with classical innate immune
cells. Stimulation of cardiac fibroblasts TLR9 was also found to attenuate
migration and proliferation, but did not influence myofibroblast differentiation
in vitro. Finally, results from in vivo TLR9-stimulation with subsequent
fractionation of specific cardiac cell-types (cardiac myocytes, CD45+ cells,
CD31+ cells and cardiac fibroblast-enriched cell-fractions) corroborated our in
vitro data and provided evidence of differentiated cell-specific cardiac
responses. Thus, we conclude that cardiac fibroblast may constitute a significant
TLR9 responder cell within the myocardium and, further, that such receptor
activity may impact important cardiac fibroblast cellular functions.
PMID- 25126742
TI - Single Si nanowire (diameter <= 100 nm) based polarization sensitive near
infrared photodetector with ultra-high responsivity.
AB - We report the fabrication and optical response of boron-doped single silicon
nanowire-based metal-semiconductor-metal photodetector. Typical single nanowire
devices with diameter of ~80-100 nm and electrode spacing of ~1 MUm were made
using electron-beam lithography from nanowires, grown by a metal-assisted
chemical etching process. A high responsivity, of the order of 10(4) A W(-1), was
observed even at zero bias in a single nanowire photodetector with peak
responsivity in the near-infrared region. The responsivity was found to increase
with increasing bias and decreasing nanowire diameter. Finite element based
optical simulation was proposed to explain the diameter dependent performance of
a single nanowire. The observed photoresponse is sensitive to the polarization of
exciting light source, allowing the device to act as a polarization-dependent
near-infrared photodetector.
PMID- 25126741
TI - Clinical outcomes of penetrating keratoplasty performed with the VisuMax
femtosecond laser system and comparison with conventional penetrating
keratoplasty.
AB - PURPOSE: To assess the clinical outcomes of femtosecond laser-assisted
keratoplasty (FLAK) using the VisuMax femtosecond laser system, and to compare
them with those of conventional penetrating keratoplasty (PK). METHODS: We
retrospectively examined 20 eyes of 20 consecutive patients undergoing FLAK and
20 eyes of 20 age- and diagnosis-matched patients undergoing conventional PK. We
quantitatively assessed corneal astigmatism, refractive astigmatism, and
corrected visual acuity, 1, 3, and 6 months postoperatively, and endothelial cell
density 6 months postoperatively. RESULTS: Corneal and refractive astigmatism
after FLAK were significantly lower after FLAK than that after conventional PK at
3 and 6 months postoperatively (p = 0.04 and p = 0.03, respectively, Mann-Whitney
U test). FLAK provided significantly faster visual recovery than conventional PK
at 1 month postoperatively (p = 0.02), but not at 3 and 6 months postoperatively
(p = 0.52 and p = 0.80, respectively). We found no significant differences in the
change in endothelial cell density between the two groups (p = 0.30).
CONCLUSIONS: FLAK using the VisuMax femtosecond laser system induces
significantly less corneal and refractive astigmatism than conventional PK, and
provides significantly faster visual recovery in the early postoperative period,
possibly because the geometry of the donor-recipient matching is more
physiological and requires less tight sutures. It is suggested that FLAK has
advantages over conventional PK, in terms of astigmatism and fast visual
recovery.
PMID- 25126743
TI - Epigenetic inactivation of inositol polyphosphate 4-phosphatase B (INPP4B), a
regulator of PI3K/AKT signaling pathway in EBV-associated nasopharyngeal
carcinoma.
AB - Nasopharyngeal carcinoma (NPC) is a common viral-associated neoplasm in which
multiple signaling cascades are interfered with by Epstein-Bar virus (EBV) latent
proteins and various genetic alterations. Aside from the previously reported
PIK3CA amplification, we examined the role of INPP4B, a negative regulator of the
PI3K/AKT signaling pathway in the development of NPC. By RT-PCR and Western
blotting, we revealed that the expression of INPP4B was down-regulated in all
five established EBV-positive tumor lines. While INPP4B was consistently
expressed in normal nasopharyngeal epithelial cells, downregulation of INPP4B was
found in 32/65 (49.2%) of primary tumors by immunohistochemistry. Furthermore,
our study also demonstrated the hypermethylation of the 5'CpG island of INPP4B in
the tumors in which INPP4B transcription was downregulated. Notably, the re
expression of INPP4B was detected in the NPC cells treated with the demethylation
agent (5-aza-2'deoxycytidine). Our study showed that promoter hypermethylation
was the major mechanism for transcriptional silencing of INPP4B in NPC.
Furthermore, restoration of INPP4B expression significantly suppressed PI3K/AKT
downstream signals in the NPC C666-1 cells. In vivo growth inhibition was clearly
demonstrated in the tumor cells stably expressing INPP4B. The findings indicate
that epigenetic inactivation of INPP4B is one of the key mechanisms in activating
PI3K/AKT signaling cascade and playing a role in the tumorigenesis of NPC.
PMID- 25126744
TI - De novo assembly of the perennial ryegrass transcriptome using an RNA-Seq
strategy.
AB - BACKGROUND: Perennial ryegrass is a highly heterozygous outbreeding grass species
used for turf and forage production. Heterozygosity can affect de-Bruijn graph
assembly making de novo transcriptome assembly of species such as perennial
ryegrass challenging. Creating a reference transcriptome from a homozygous
perennial ryegrass genotype can circumvent the challenge of heterozygosity. The
goals of this study were to perform RNA-sequencing on multiple tissues from a
highly inbred genotype to develop a reference transcriptome. This was
complemented with RNA-sequencing of a highly heterozygous genotype for SNP
calling. RESULT: De novo transcriptome assembly of the inbred genotype created
185,833 transcripts with an average length of 830 base pairs. Within the inbred
reference transcriptome 78,560 predicted open reading frames were found of which
24,434 were predicted as complete. Functional annotation found 50,890 transcripts
with a BLASTp hit from the Swiss-Prot non-redundant database, 58,941 transcripts
with a Pfam protein domain and 1,151 transcripts encoding putative secreted
peptides. To evaluate the reference transcriptome we targeted the high-affinity
K+ transporter gene family and found multiple orthologs. Using the longest unique
open reading frames as the reference sequence, 64,242 single nucleotide
polymorphisms were found. One thousand sixty one open reading frames from the
inbred genotype contained heterozygous sites, confirming the high degree of
homozygosity. CONCLUSION: Our study has developed an annotated, comprehensive
transcriptome reference for perennial ryegrass that can aid in determining
genetic variation, expression analysis, genome annotation, and gene mapping.
PMID- 25126745
TI - T cell IFN-gamma suppression following alcohol and burn injury is independent of
miRNA155.
AB - miRNA155 has been implicated in normal T cell function and their differentiations
into the Th1 subtype. We have shown that acute alcohol (ethanol) intoxication
combined with burn injury suppresses T cell IFN-gamma release. Herein, we
examined whether the decrease in IFN-gamma is resulted from altered expression of
miRNA155 and transcription factors--NFAT, Tbx21, Jun and Fos--in T cells
following ethanol and burn injury. Mice received ethanol (~3 g/Kg) 4 hours prior
to ~12.5% total body surface area sham or burn injury and were sacrificed one day
after injury. Splenic T cells were harvested and cultured with anti-CD3 (2 ug/ml)
in the presence or absence of rIL-12 (10 ng/ml) or PMA (10 ng/ml) plus ionomycin
(50 ng/ml) for 48 hours. We observed a significant decrease in miRNA155, NFAT,
Tbx21, Jun and Fos expression as well as IFN-gamma release in T cells cultured
with anti-CD3 following ethanol and burn injury compared with shams. The co
treatment of T cells with rIL-12 prevented the decrease in IFN-gamma and NFAT,
Tbx21, Jun and Fos, but not miRNA155. In contrast, the co-treatment with PMA plus
ionomycin normalized the expression of NFAT. It did not prevent the decrease in
IFN-gamma, Tbx21, Jun, Fos and miRNA155. Finally, results obtained in miRNA155-/-
mice did not show any change in T cell release of IFN-gamma or expression of
nuclear factors compared to wildtype mice. Together, these findings suggest that
while ethanol and burn injury decreases the expression of miRNA155, it may not be
involved in decreased IFN-gamma under those conditions.
PMID- 25126746
TI - Do cells contribute to tendon and ligament biomechanics?
AB - INTRODUCTION: Acellular scaffolds are increasingly used for the surgical repair
of tendon injury and ligament tears. Despite this increased use, very little data
exist directly comparing acellular scaffolds and their native counterparts. Such
a comparison would help establish the effectiveness of the acellularization
procedure of human tissues. Furthermore, such a comparison would help estimate
the influence of cells in ligament and tendon stability and give insight into the
effects of acellularization on collagen. MATERIAL AND METHODS: Eighteen human
iliotibial tract samples were obtained from nine body donors. Nine samples were
acellularized with sodium dodecyl sulphate (SDS), while nine counterparts from
the same donors remained in the native condition. The ends of all samples were
plastinated to minimize material slippage. Their water content was adjusted to
69%, using the osmotic stress technique to exclude water content-related
alterations of the mechanical properties. Uniaxial tensile testing was performed
to obtain the elastic modulus, ultimate stress and maximum strain. The
effectiveness of the acellularization procedure was histologically verified by
means of a DNA assay. RESULTS: The histology samples showed a complete removal of
the cells, an extensive, yet incomplete removal of the DNA content and
alterations to the extracellular collagen. Tensile properties of the tract
samples such as elastic modulus and ultimate stress were unaffected by
acellularization with the exception of maximum strain. DISCUSSION: The data
indicate that cells influence the mechanical properties of ligaments and tendons
in vitro to a negligible extent. Moreover, acellularization with SDS alters
material properties to a minor extent, indicating that this method provides a
biomechanical match in ligament and tendon reconstruction. However, the given
protocol insufficiently removes DNA. This may increase the potential for
transplant rejection when acellular tract scaffolds are used in soft tissue
repair. Further research will help optimize the SDS-protocol for clinical
application.
PMID- 25126747
TI - Increased expression of CCN2, epithelial membrane antigen, and fibroblast
activation protein in hepatocellular carcinoma with fibrous stroma showing
aggressive behavior.
AB - Tumor behavior is affected by the tumor microenvironment, composed of cancer
associated fibroblasts (CAFs). Meanwhile, hepatocellular carcinomas (HCC) with
fibrous stroma reportedly exhibit aggressive behavior suggestive of tumor-stroma
interaction. However, evidence of the crosstalk remains unclear. In this study,
CCN2, epithelial membrane antigen (EMA), fibroblast activation protein (FAP), and
keratin 19 (K19) expression was studied in 314 HCCs (cohort 1), 42 scirrhous HCCs
(cohort 2), and 36 chronic hepatitis/cirrhosis specimens by immunohistochemistry.
Clinicopathological parameters were analyzed according to the expressions of
these markers. In tumor epithelial cells from cohort 1, CCN2 and EMA were
expressed in 15.3% and 17.2%, respectively, and their expressions were more
frequent in HCCs with fibrous stroma (>=5% of tumor area) than those without
(P<0.05 for all); CCN2 expression was well correlated with K19 and EMA
expression. In tumor stromal cells, FAP expression was found in 6.7%. In cohort
2, CCN2, EMA, and FAP expression was noted in 40.5%, 40.5%, and 66.7%,
respectively, which was more frequent than that in cohort 1 (P<0.05 for all).
Additionally, EMA expression was associated with the expression of K19, CCN2, and
FAP (P<0.05 for all); EMA expressing tumor epithelial cells showed a topographic
closeness to FAP-expressing CAFs. Analysis of disease-free survival revealed CCN2
expression to be a worse prognostic factor in both cohort 1 (P = 0.005) and
cohort 2 (P = 0.023), as well as EMA as a worse prognostic factor in cohort 2 (P
= 0.048). In conclusion, expression of CCN2, EMA, and FAP may be involved in the
activation of CAFs in HCC, giving rise to aggressive behavior. Significant
correlation between EMA-expressing tumor cells and FAP-expressing CAFs and their
topographic closeness suggests possible cross-talk between tumor epithelial cells
and stromal cells in the tumor microenvironment of HCC.
PMID- 25126749
TI - MafA is required for postnatal proliferation of pancreatic beta-cells.
AB - The postnatal proliferation and maturation of insulin-secreting pancreatic beta
cells are critical for glucose metabolism and disease development in adults.
Elucidation of the molecular mechanisms underlying these events will be
beneficial to direct the differentiation of stem cells into functional beta
cells. Maturation of beta-cells is accompanied by increased expression of MafA,
an insulin gene transcription factor. Transcriptome analysis of MafA knockout
islets revealed MafA is required for the expression of several molecules critical
for beta-cell function, including Glut2, ZnT8, Granuphilin, Vdr, Pcsk1 and
Urocortin 3, as well as Prolactin receptor (Prlr) and its downstream target
Cyclin D2 (Ccnd2). Inhibition of MafA expression in mouse islets or beta-cell
lines resulted in reduced expression of Prlr and Ccnd2, and MafA transactivated
the Prlr promoter. Stimulation of beta-cells by prolactin resulted in the
phosphorylation and translocation of Stat5B and an increased nuclear pool of
Ccnd2 via Prlr and Jak2. Consistent with these results, the loss of MafA resulted
in impaired proliferation of beta-cells at 4 weeks of age. These results suggest
that MafA regulates the postnatal proliferation of beta-cells via prolactin
signaling.
PMID- 25126752
TI - Attentional cueing by cross-modal congruency produces both facilitation and
inhibition on short-term visual recognition.
AB - The attentional modulation of performance in a memory task, comparable to the one
obtained in a perceptual task, is at the focus of contemporary research. We
hypothesized that a biphasic effect (namely, facilitation followed by inhibition)
can be obtained in visual working memory when attention is cued towards one item
of the memorandum and participants must recognize a delayed probe as being
identical to any item of the memorandum. In every trial, a delayed spiky/curvy
probe appeared centrally, to be matched with the same-category shape maintained
in visual working memory which could be either physically identical (positive
trials) or only categorically similar (negative trials). To orient the
participant's attention towards a selected portion of a two-item memorandum, a
(tzk/wow) sound was played simultaneously with two lateral visual shapes (one
spiky and one curved). Our results indicate that an exogenous attentional shift
during perception of the memorandum, induced by a congruent audio-visual pairing,
first facilitates and then inhibits the recognition of a cued item (but not of a
non-cued item) stored in visual working memory. A coherent pattern of individual
differences emerged, indicating that the amount of early facilitation in
congruent-sound trials was negatively correlated with recognition sensitivity in
no-sound trials (suggesting that the inverse effectiveness rule may also apply to
memory) and positively correlated with later inhibition, as well as with the self
reported susceptibility to memory failures.
PMID- 25126753
TI - A correlative approach to segmenting phases and ferrite morphologies in
transformation-induced plasticity steel using electron back-scattering
diffraction and energy dispersive X-ray spectroscopy.
AB - Using a combination of electron back-scattering diffraction and energy dispersive
X-ray spectroscopy data, a segmentation procedure was developed to
comprehensively distinguish austenite, martensite, polygonal ferrite, ferrite in
granular bainite and bainitic ferrite laths in a thermo-mechanically processed
low-Si, high-Al transformation-induced plasticity steel. The efficacy of the
ferrite morphologies segmentation procedure was verified by transmission electron
microscopy. The variation in carbon content between the ferrite in granular
bainite and bainitic ferrite laths was explained on the basis of carbon
partitioning during their growth.
PMID- 25126750
TI - Inhibition of HMGB1-induced angiogenesis by cilostazol via SIRT1 activation in
synovial fibroblasts from rheumatoid arthritis.
AB - High mobility group box chromosomal protein 1 (HMGB-1) released from injured
cells plays an important role in the development of arthritis. This study
investigated the anti-angiogenic effects of cilostazol in collagen-induced
arthritis (CIA) of mice, and the underlying mechanisms involved. The expressions
of HIF-1alpha, VEGF, NF-kappaB p65 and SIRT1 in synovial fibroblasts obtained
from rheumatoid arthritis (RA) patients were assessed by Western blotting, and in
vitro and in vivo angiogenesis were analyzed. Tube formations by human
microvascular endothelial cells (HMVECs) were significantly increased by direct
exposure to HMGB1 or to conditioned medium derived from HMGB1-stimulated RA
fibroblasts, and these increases were attenuated by cilostazol, the latter of
which was blocked by sirtinol. HMGB1 increased the expression of HIF-1alpha and
VEGF and concomitantly increased nuclear NF-kappaB p65 and DNA binding activity,
but these effects of HMGB1 were inhibited by cilostazol. SIRT1 protein expression
was time-dependently decreased (3-24 hr) by HMGB1, which was recovered by
pretreatment with cilostazol (1-30 uM) or resveratrol, accompanying with
increased SIRT1 deacetylase activity. In the tibiotarsal joint tissues of CIA
mice treated with vehicle, HIF-1alpha- and VEGF-positive spots and CD31 staining
were markedly exaggerated, whereas SIRT1 immunofluorescence was diminished. These
variables were wholly reversed in cilostazol (30 mg/kg/day)-treated mice.
Furthermore, number of blood vessels stained by von Willebrand factor antibody
was significantly lower in cilostazol-treated CIA mice. Summarizing, cilostazol
activated SIRT1 and inhibited NF-kappaB-mediated transcription, thereby
suppressing the expression of HIF-1alpha and VEGF. In addition, cilostazol caused
HIF-1alpha deacetylation by enhancing SIRT1 activity and reduced VEGF production,
thereby had an anti-angiogenic effect in vitro studies and in CIA murine model.
PMID- 25126755
TI - Overview of research on the mental health impact of violence in the Middle East
in light of the Arab Spring.
AB - This is a baseline of published research in the trauma field by Arab researchers.
It highlights groundbreaking attempts by Arab researchers to investigate the
mental health impact of violence in their countries before the Arab Spring. Peer
reviewed articles (N = 157) were identified through computerized searches in
PubMed, PsycINFO, Google Scholar, and Pilots Database, 1995 to 2012. A synopsis
of the published research included (a) country, (b) screening instruments, (c)
sample size, (d) methods, and (e) results. The findings reveal that domestic
violence attracted most attention after civil strife in Palestine and Lebanon.
Torture survivors and victims of sexual violence received little attention. Study
instruments were borrowed from Western researchers without being validated within
local Arab cultures. No clinical outcome studies were found. In light of the Arab
Spring, it is urgent that Arab researchers conduct studies that are evidence
based and culturally valid addressing the mental health care of all traumatized
citizens.
PMID- 25126754
TI - Prevalence and predictors of mental disorders in intentionally and
unintentionally injured emergency center patients.
AB - Little is known about the prevalence and predictors of mental disorders among
injured emergency center (EC) patients in low- and middle-income countries
(LMICs). Patients presenting with either an intentional or unintentional injury
were recruited (N = 200). Mental health, injury, and psychological trauma
histories were assessed. Descriptive statistics and logistic regressions were
conducted, and predictors of current mental disorder were identified. Diagnostic
criteria for a current mental disorder, including substance use disorders, were
met by 59.5% of the participants. Compared with those with an unintentional
injury, the intentionally injured participants were more likely to be diagnosed
with a current mental disorder (66.9% vs. 48.8%, p = .01). High frequencies of
previous intentional injuries predicted for current mental disorder (OR = 1.46,
95% CI 1.08-1.98), whereas male gender and witnessed community violence predicted
substance use disorder diagnoses. The findings indicate that injured EC patients,
particularly those with intentional injuries, are at risk for mental disorders.
Psychosocial interventions in the EC context can potentially make an important
contribution in reducing the burden of mental disorders and injuries in LMICs.
PMID- 25126756
TI - Aquatic metagenomes implicate Thaumarchaeota in global cobalamin production.
AB - Cobalamin (vitamin B12) is a complex metabolite and essential cofactor required
by many branches of life, including most eukaryotic phytoplankton. Algae and
other cobalamin auxotrophs rely on environmental cobalamin supplied from a
relatively small set of cobalamin-producing prokaryotic taxa. Although several
Bacteria have been implicated in cobalamin biosynthesis and associated with algal
symbiosis, the involvement of Archaea in cobalamin production is poorly
understood, especially with respect to the Thaumarchaeota. Based on the detection
of cobalamin synthesis genes in available thaumarchaeotal genomes, we
hypothesized that Thaumarchaeota, which are ubiquitous and abundant in aquatic
environments, have an important role in cobalamin biosynthesis within global
aquatic ecosystems. To test this hypothesis, we examined cobalamin synthesis
genes across sequenced thaumarchaeotal genomes and 430 metagenomes from a diverse
range of marine, freshwater and hypersaline environments. Our analysis
demonstrates that all available thaumarchaeotal genomes possess cobalamin
synthesis genes, predominantly from the anaerobic pathway, suggesting widespread
genetic capacity for cobalamin synthesis. Furthermore, although bacterial
cobalamin genes dominated most surface marine metagenomes, thaumarchaeotal
cobalamin genes dominated metagenomes from polar marine environments, increased
with depth in marine water columns, and displayed seasonality, with increased
winter abundance observed in time-series datasets (e.g., L4 surface water in the
English Channel). Our results also suggest niche partitioning between
thaumarchaeotal and cyanobacterial ribosomal and cobalamin synthesis genes across
all metagenomic datasets analyzed. These results provide strong evidence for
specific biogeographical distributions of thaumarchaeotal cobalamin genes,
expanding our understanding of the global biogeochemical roles played by
Thaumarchaeota in aquatic environments.
PMID- 25126757
TI - Viruses accumulate in aging infection centers of a fungal forest pathogen.
AB - Fungal viruses (mycoviruses) with RNA genomes are believed to lack extracellular
infective particles. These viruses are transmitted laterally among fungal strains
through mycelial anastomoses or vertically via their infected spores, but little
is known regarding their prevalence and patterns of dispersal under natural
conditions. Here, we examined, in detail, the spatial and temporal changes in a
mycovirus community and its host fungus Heterobasidion parviporum, the most
devastating fungal pathogen of conifers in the Boreal forest region. During the 7
year sampling period, viruses accumulated in clonal host individuals as a result
of indigenous viruses spreading within and between clones as well as novel
strains arriving via airborne spores. Viral community changes produced pockets of
heterogeneity within large H. parviporum clones. The appearance of novel viral
infections in aging clones indicated that transient cell-to-cell contacts between
Heterobasidion strains are likely to occur more frequently than what was inferred
from genotypic analyses. Intraspecific variation was low among the three
partitivirus species at the study site, whereas the unassigned viral species
HetRV6 was highly polymorphic. The accumulation of point mutations during
persistent infections resulted in viral diversification, that is, the presence of
nearly identical viral sequence variants within single clones. Our results also
suggest that co-infections by distantly related viral species are more stable
than those between conspecific strains, and mutual exclusion may play a role in
determining mycoviral communities.
PMID- 25126758
TI - Disturbance and temporal partitioning of the activated sludge metacommunity.
AB - The resilience of microbial communities to press disturbances and whether
ecosystem function is governed by microbial composition or by the environment
have not been empirically tested. To address these issues, a whole-ecosystem
manipulation was performed in a full-scale activated sludge wastewater treatment
plant. The parameter solids retention time (SRT) was used to manipulate microbial
composition, which started at 30 days, then decreased to 12 and 3 days, before
operation was restored to starting conditions (30-day SRT). Activated sludge
samples were collected throughout the 313-day time series in parallel with
bioreactor performance ('ecosystem function'). Bacterial small subunit (SSU) rRNA
genes were surveyed from sludge samples resulting in a sequence library of
>417,000 SSU rRNA genes. A shift in community composition was observed for 12-
and 3-day SRTs. The composition was altered such that r-strategists were enriched
in the system during the 3-day SRT, whereas K-strategists were only present at
SRTs?12 days. This shift corresponded to loss of ecosystem functions
(nitrification, denitrification and biological phosphorus removal) for SRTs?12
days. Upon return to a 30-day SRT, complete recovery of the bioreactor
performance was observed after 54 days despite an incomplete recovery of
bacterial diversity. In addition, a different, yet phylogenetically related,
community with fewer of its original rare members displaced the pre-disturbance
community. Our results support the hypothesis that microbial ecosystems harbor
functionally redundant phylotypes with regard to general ecosystem functions
(carbon oxidation, nitrification, denitrification and phosphorus accumulation).
However, the impacts of decreased rare phylotype membership on ecosystem
stability and micropollutant removal remain unknown.
PMID- 25126759
TI - Aqueous leaf extract of Jatropha gossypiifolia L. (Euphorbiaceae) inhibits
enzymatic and biological actions of Bothrops jararaca snake venom.
AB - Snakebites are a serious public health problem due their high morbi-mortality.
The main available specific treatment is the antivenom serum therapy, which has
some disadvantages, such as poor neutralization of local effects, risk of
immunological reactions, high cost and difficult access in some regions. In this
context, the search for alternative therapies is relevant. Therefore, the aim of
this study was to evaluate the antiophidic properties of Jatropha gossypiifolia,
a medicinal plant used in folk medicine to treat snakebites. The aqueous leaf
extract of the plant was prepared by decoction and phytochemical analysis
revealed the presence of sugars, alkaloids, flavonoids, tannins, terpenes and/or
steroids and proteins. The extract was able to inhibit enzymatic and biologic
activities induced by Bothrops jararaca snake venom in vitro and in vivo. The
blood incoagulability was efficiently inhibited by the extract by oral route. The
hemorrhagic and edematogenic local effects were also inhibited, the former by up
to 56% and the latter by 100%, in animals treated with extract by oral and
intraperitoneal routes, respectively. The inhibition of myotoxic action of B.
jararaca reached almost 100%. According to enzymatic tests performed, it is
possible to suggest that the antiophidic activity may be due an inhibitory action
upon snake venom metalloproteinases (SVMPs) and/or serine proteinases (SVSPs),
including fibrinogenolytic enzymes, clotting factors activators and thrombin like
enzymes (SVTLEs), as well upon catalytically inactive phospholipases A2 (Lys49
PLA2). Anti-inflammatory activity, at least partially, could also be related to
the inhibition of local effects. Additionally, protein precipitating and
antioxidant activities may also be important features contributing to the
activity presented. In conclusion, the results demonstrate the potential
antiophidic activity of J. gossypiifolia extract, including its significant
action upon local effects, suggesting that it may be used as a new source of
bioactive molecules against bothropic venom.
PMID- 25126760
TI - Targeted disruption of the intracellular domain of receptor FgfrL1 in mice.
AB - FgfrL1 is the fifth member of the fibroblast growth factor receptor (Fgfr)
family. Studies with FgfrL1 deficient mice have demonstrated that the gene plays
an important role during embryonic development. FgfrL1 knock-out mice die at
birth as they have a malformed diaphragm and lack metanephric kidneys. Similar to
the classical Fgfrs, the FgfrL1 protein contains an extracellular part composed
of three Ig-like domains that interact with Fgf ligands and heparin. However, the
intracellular part of FgfrL1 is not related to the classical receptors and does
not possess any tyrosine kinase activity. Curiously enough, the amino acid
sequence of this domain is barely conserved among different species, with the
exception of three motifs, namely a dileucine peptide, a tandem tyrosine-based
motif YXXPhi and a histidine-rich sequence. To investigate the function of the
intracellular domain of FgfrL1, we have prepared genetically modified mice that
lack the three conserved sequence motifs, but instead contain a GFP cassette
(FgfrL1DeltaC-GFP). To our surprise, homozygous FgfrL1DeltaC-GFP knock-in mice
are viable, fertile and phenotypically normal. They do not exhibit any
alterations in the diaphragm or the kidney, except for a slight reduction in the
number of glomeruli that does not appear to affect life expectancy. In addition,
the pancreas of both FgfrL1DeltaC-GFP knock-in and FgfrL1 knock-out mice do not
show any disturbances in the production of insulin, in contrast to what has been
suggested by recent studies. Thus, the conserved motifs of the intracellular
FgfrL1 domain are dispensable for organogenesis and normal life. We conclude that
the extracellular domain of the protein must conduct the vital functions of
FgfrL1.
PMID- 25126762
TI - Malignant self-regard: a self-structure enhancing the understanding of
masochistic, depressive, and vulnerably narcissistic personalities.
AB - Several personality disorders have been prominent in the clinical literature but
have been inadequately recognized in the diagnostic manuals. This group includes
masochistic, self-defeating, depressive, and vulnerably narcissistic personality
disorders. The theoretical and empirical relationship of these disorders is
reviewed. It is proposed that the construct of malignant self-regard may account
for the similarities among them. The construct describes these personality types
as being fundamentally related through problematic manifestations of self
structure. The article discusses the diagnostic value of such a construct and the
implications of a psychodynamically informed framework for classifying
personality pathology.
PMID- 25126763
TI - Disordered self in the schizophrenia spectrum: a clinical and research
perspective.
AB - This article explores the phenomenological and empirical rediscovery of anomalous
self-experience as a core feature of the schizophrenia spectrum disorders and
presents the current status of research in this field. Historically, a disordered
self was considered to be a constitutive phenotype of schizophrenia. Although the
notion of a disordered self has continued to appear occasionally over the years
mainly in the phenomenologically or psychodynamically oriented literature-this
notion was usually considered as a theoretical construct rather than as referring
to concretely lived anomalous experiences. Empirical research on the disorders of
self-experience in schizophrenia can be traced back to the US-Denmark
psychopathological collaboration in the well-known adoption and high-risk
studies, which aimed at identifying trait or phenotypic vulnerability features.
This research was later followed by clinical work with first-admission
schizophrenia patients. We offer clinical descriptions of anomalous self
experience and outline the phenomenological structures of subjectivity that are
needed for grasping the nature of these anomalous experiential phenomena. What
appears to underlie these experiences is an instability of the first-person
perspective that threatens the basic experience of being a self-coinciding,
embodied, demarcated, and persisting subject of awareness. We summarize a series
of empirical studies targeting self-experience in schizophrenia performed prior
to and after the construction of a phenomenologically oriented psychometric
instrument for assessing anomalies of self-experience, the Examination of
Anomalous Self-Experience (EASE). These empirical studies support the classic
clinical intuition that anomalous self-experiences form a central phenotype of
schizophrenia. Implications for diagnosis and research are briefly discussed.
PMID- 25126761
TI - Validity of heart failure diagnoses in administrative databases: a systematic
review and meta-analysis.
AB - OBJECTIVE: Heart failure (HF) is an important covariate and outcome in studies of
elderly populations and cardiovascular disease cohorts, among others.
Administrative data is increasingly being used for long-term clinical research in
these populations. We aimed to conduct the first systematic review and meta
analysis of studies reporting on the validity of diagnostic codes for identifying
HF in administrative data. METHODS: MEDLINE and EMBASE were searched (inception
to November 2010) for studies: (a) Using administrative data to identify HF; or
(b) Evaluating the validity of HF codes in administrative data; and (c) Reporting
validation statistics (sensitivity, specificity, positive predictive value [PPV],
negative predictive value, or Kappa scores) for HF, or data sufficient for their
calculation. Additional articles were located by hand search (up to February
2011) of original papers. Data were extracted by two independent reviewers;
article quality was assessed using the Quality Assessment of Diagnostic Accuracy
Studies tool. Using a random-effects model, pooled sensitivity and specificity
values were produced, along with estimates of the positive (LR+) and negative (LR
) likelihood ratios, and diagnostic odds ratios (DOR = LR+/LR-) of HF codes.
RESULTS: Nineteen studies published from 1999-2009 were included in the
qualitative review. Specificity was >=95% in all studies and PPV was >=87% in the
majority, but sensitivity was lower (>=69% in >=50% of studies). In a meta
analysis of the 11 studies reporting sensitivity and specificity values, the
pooled sensitivity was 75.3% (95% CI: 74.7-75.9) and specificity was 96.8% (95%
CI: 96.8-96.9). The pooled LR+ was 51.9 (20.5-131.6), the LR- was 0.27 (0.20
0.37), and the DOR was 186.5 (96.8-359.2). CONCLUSIONS: While most HF diagnoses
in administrative databases do correspond to true HF cases, about one-quarter of
HF cases are not captured. The use of broader search parameters, along with
laboratory and prescription medication data, may help identify more cases.
PMID- 25126766
TI - Fluorescence fluctuation microscopy: a diversified arsenal of methods to
investigate molecular dynamics inside cells.
AB - Fluorescence microscopy provides insight into the subcellular organization of
biological functions. However, images are snap shots averaging over a highly
dynamic molecular system. Fluorescence fluctuation microscopy, employing similar
detection technology, encompasses a powerful arsenal of analysis tools that
investigate the molecular heterogeneity in space and time. Analyzing signal
fluctuations from small ensembles (several hundred particles) reveals their
concentration, the stoichiometry, the stochastic motion, as well as superimposed
signatures of the environment such as spatial confinement and binding events.
Thus, fluctuation analysis provides access to dynamic molecular properties that
can be used to build physical models of cellular processes. In the last decade
these methods experienced a remarkable diversification, which we revisit here
with a particular focus on live cell applications.
PMID- 25126765
TI - High-speed AFM imaging.
AB - Proteins are dynamic in nature and function at the single molecule level. To
achieve a straightforward and in-depth understanding of their underlying
functional mechanism, we need to directly observe protein molecules at work at
high resolution, without the use of protein-attached markers. To realize such
objectives, high-speed atomic force microscopy (HS-AFM) has been developed and
recently its capability has been fully established. This approach opens a new
avenue to directly and closely observe individual molecules at submolecular
spatial resolution and sub-100 ms time resolution. The captured molecular movies
of proteins directly report and provide great insights into how the proteins
function. Moreover, the very recent progress of HS-AFM technology has extended
its use to the observation of dynamic cellular processes. In this article, I
review imaging studies to show the innovative power and potential of this new
microscopy.
PMID- 25126764
TI - Low molecular weight hyaluronan mediated CD44 dependent induction of IL-6 and
chemokines in human dermal fibroblasts potentiates innate immune response.
AB - Complex regulation of the wound healing process involves multiple interactions
among stromal tissue cells, inflammatory cells, and the extracellular matrix. Low
molecular weight hyaluronan (LMW HA) derived from the degradation of high
molecular weight hyaluronan (HMW HA) is suggested to activate cells involved in
wound healing through interaction with HA receptors. In particular, receptor CD44
is suggested to mediate cell response to HA of different MW, being the main cell
surface HA receptor in stromal tissue and immune cells. However, the response of
dermal fibroblasts, the key players in granulation tissue formation within the
wound healing process, to LMW HA and their importance for the activation of
immune cells is unclear. In this study we show that LMW HA (4.3kDa) induced pro
inflammatory cytokine IL-6 and chemokines IL-8, CXCL1, CXCL2, CXCL6 and CCL8 gene
expression in normal human dermal fibroblasts (NHDF) that was further confirmed
by increased levels of IL-6 and IL-8 in cell culture supernatants. Conversely,
NHDF treated by HMW HA revealed a tendency to decrease the gene expression of
these cytokine and chemokines when compared to untreated control. The blockage of
CD44 expression by siRNA resulted in the attenuation of IL-6 and chemokines
expression in LMW HA treated NHDF suggesting the involvement of CD44 in LMW HA
mediated NHDF activation. The importance of pro-inflammatory mediators produced
by LMW HA triggered NHDF was evaluated by significant activation of blood
leukocytes exhibited as increased production of IL-6 and TNF-alpha. Conclusively,
we demonstrated a pro-inflammatory response of dermal fibroblasts to LMW HA that
was transferred to leukocytes indicating the significance of LMW HA in the
inflammatory process development during the wound healing process.
PMID- 25126768
TI - Novel Pigtail Cannula for a Canalicular-Involving Eyelid Laceration.
AB - An 89-year-old woman presented with a canalicular-involving laceration/avulsion
of the right lower eyelid after a fall. The inferior canaliculus was severed deep
within the wound, and the ends were difficult to identify. Novel pigtail
cannulas, designed by the authors, were used for lacrimal system intubation and
suture passage. Satisfactory cosmetic and functional results were achieved. These
cannulas facilitate repair by integrating multiple functionalities in a single
instrument. Once a cannula has been inserted and rotated, the location of fluid
egress provides important clues. If injected saline appears in the nasopharynx
but not in the wound, absence of a common canaliculus can be suspected. Injection
of viscoelastic, air or fluorescein-impregnated saline also permits easier
identification of the cut end of the canaliculus within the wound and facilitates
appropriate rotation of the pigtail.
PMID- 25126767
TI - Neurostimulation of the lacrimal nerve for enhanced tear production.
AB - PURPOSE: To design a proof-of-concept study to assess the effect of lacrimal
nerve stimulation (LNS) with an implantable pulse generator (IPG) to increase
aqueous tear production. METHODS: Experimental animal study design of 6 Dutch
Belted rabbits. Ultra high-resolution optical coherence tomography (UHR-OCT)
quantified tear production by measuring the baseline tear volume of each rabbit's
OD and OS. A neurostimulator was implanted adjacent to the right lacrimal nerve.
After 2 minutes of LNS (100 MUs, 1.6 mA, 20 Hz, 5-8 V), the tear volumes were
measured with UHR-OCT. The change in tear volume was quantified and compared with
the nonstimulated OS. Three rabbits underwent chronic LNS (100 MUs, 1.6 mA, 10
Hz, 2 V) and their lacrimal glands were harvested for histopathologic analysis.
RESULTS: The UHR-OCT imaging of the OD tear volume showed a 441% average increase
in tear production after LNS as a percent of baseline. After stimulation, OD had
statistically significant greater increase in tear volumes than OS (p = 0.028,
Wilcoxon test). Poststimulation OD tear volumes were significantly greater
compared with baseline (p = 0.028, Wilcoxon test). Histopathologic examination of
the lacrimal glands showed no discernible tissue damage from chronic
neurostimulation. In addition, there were no gross adverse effects on the general
well-being of the animals due to chronic stimulation. CONCLUSIONS: LNS with an
IPG appears to increase aqueous tear production. Chronic LNS showed no
histopathologic lacrimal gland damage. This study suggests that LNS is a
promising new treatment strategy to increase aqueous tear production.
PMID- 25126769
TI - Risk of ocular blood splatter during oculofacial plastic surgery.
AB - PURPOSE: To assess intraoperative blood splatter to the ocular surface and adnexa
during oculofacial surgery. METHODS: Four surgeons and multiple assistants at
three separate locations wore a total of 331 protective eye shields during 131
surgeries. Postoperatively, a luminol blood detection system was used to identify
blood splatter on the shields. In the event of positive blood splatter, the total
number of blood spots was counted. Controls were used to verify the blood
detection protocol. A postoperative questionnaire was given to all surgeons and
assistants after each case, and they were asked whether intraoperative blood
splatter was noticed. RESULTS: Blood was detected on 61% of eye shields and in a
total of 80% of surgical cases. However, only 2% of blood splatters were
recognized intraoperatively by the surgical participants. There was no
significant difference in the splatter rate between surgeons (64%), assistants
(60%), and surgical technicians (58%) (p = 0.69). Shields worn during full
thickness eyelid procedures, direct brow lifting, orbitotomy with bony window,
and orbital fracture repairs were more likely to be splattered (p = 0.03), and
there was a significant difference between splatter rates among different
surgeons (range, 29-90%; p = 0.0004), suggesting that blood splatter rate may be
both procedure dependent and surgeon dependent. CONCLUSIONS: Mucocutaneous and
transconjunctival transmission of human immunodeficiency virus and viral
hepatitis has been documented. These results suggest that oculofacial plastic
surgeons should consider eye protection for patients with known blood-borne
diseases and in cases where blood splatter is expected. This precautionary
practice is supported by the high incidence (98%) of undetected, intraoperative
blood splatter.
PMID- 25126770
TI - Malignant melanoma of the lacrimal drainage apparatus complicating conjunctival
melanoma.
AB - PURPOSE: Melanoma of the conjunctiva may occasionally involve the lacrimal
drainage apparatus (LDA). This makes clinical management difficult. The authors
describe 5 cases of conjunctival melanoma with LDA disease and make
recommendations about its management. METHODS: Retrospective review of case notes
and histopathology reports. RESULTS: Five cases of LDA melanoma arising in
patients with conjunctival melanoma are described. All 5 had orbital exenteration
as part of their treatment. Melanoma of the LDA was clinically present at the
time of exenteration in 1 case, found unexpectedly in 2 cases, and developed
subsequent to exenteration in 2 cases. One patient died within 8 months of
exenteration from metastatic melanoma. Two patients were disease free 3 and 5
years after exenteration. One patient developed metastasis in the parotid gland 4
years after exenteration but remained disease free 7 years after exenteration.
One more patient has had a local recurrence in the maxilla and lateral nasal wall
4 years after exenteration, and after resection of that lesion and radiotherapy
is disease free after 18 months. Seventeen patients underwent orbital
exenteration for conjunctival melanoma over the period 1996-2013 at the
authors'institution, with 5 having or developing LDA disease (29%). In the same
period, there were 52 patients with conjunctival melanoma overall, with LDA
involvement occurring in 5 of 52 patients (9.6%). CONCLUSIONS: Melanoma of the
LDA may complicate conjunctival melanoma in a significant percentage of cases
having orbital exenteration. The surgical technique for orbital exenteration in
patients with conjunctival melanoma should take this into account by
intentionally removing the lacrimal sac and upper nasolacrimal duct as well as
the lacrimal canaliculi. If melanoma is found in the LDA, consideration should be
given to wider en bloc excision of the LDA.
PMID- 25126771
TI - Idiopathic Orbital Inflammation Associated With Necrotizing Scleritis and
Temporal Bone Inflammation.
AB - The authors present a case of aggressive idiopathic orbital inflammation
producing necrotizing scleritis along with synchronous tumefactive
fibroinflammatory lesion of the temporal bone. A young woman with no medical
history presented with sectoral scleritis and mildly reduced vision. Response to
initial treatment, which included topical and systemic corticosteroids, as well
as systemic nonsteroidal anti-inflammatory drugs, was limited. Over the following
months, signs of orbital inflammation developed, including ptosis, proptosis, and
limited extraocular motility. MRI revealed both orbital and ipsilateral temporal
bone masses. An orbital biopsy was performed revealing a mixed inflammatory
infiltrate, whereas a biopsy of the temporal bone mass revealed a tumefactive
fibroinflammatory lesion. Biopsy showed no histopathologic evidence of infection
nor neoplasm. The patient eventually responded to treatment with systemic
prednisone, azathioprine, and rituximab.
PMID- 25126772
TI - Dacryocystitis As the Initial Presentation of Invasive Fungal Sinusitis in
Immunocompromised Children.
AB - Sino-orbital fungal infection is a rare, but life-threatening disease seen mainly
in immunocompromised patients. While initial clinical impression may vary,
dacryocystitis has rarely been described as the initial presenting sign. The
authors present 2 pediatric cases of dacryocystitis as the initial sign of
invasive fungal sinusitis. To their knowledge, this presenting sign has not been
previously reported in the pediatric population. Management strategies and
outcomes are discussed.
PMID- 25126773
TI - Magnesium sulphate for preventing preterm birth in threatened preterm labour.
AB - BACKGROUND: Magnesium sulphate has been used in some settings as a tocolytic
agent to inhibit uterine activity in women in preterm labour with the aim of
preventing preterm birth. OBJECTIVES: To assess the effects of magnesium sulphate
therapy given to women in threatened preterm labour with the aim of preventing
preterm birth and its sequelae. SEARCH METHODS: We searched the Cochrane
Pregnancy and Childbirth Group's Trials Register (last searched 31 January 2014).
SELECTION CRITERIA: Randomised controlled trials of magnesium sulphate as the
only tocolytic, administered by any route, compared with either placebo, no
treatment or alternative tocolytic therapy (not magnesium sulphate) to women
considered to be in preterm labour. DATA COLLECTION AND ANALYSIS: At least two
review authors assessed trial eligibility and risk of bias and undertook data
extraction independently. MAIN RESULTS: The 37 included trials (total of 3571
women and over 3600 babies) were generally of moderate to high risk of bias.
Antenatal magnesium sulphate was compared with either placebo, no treatment, or a
range of alternative tocolytic agents.For the primary outcome of giving birth
within 48 hours after trial entry, no significant differences were seen between
women who received magnesium sulphate and women who did not (whether placebo/no
alternative tocolytic drug, betamimetics, calcium channel blockers, cox
inhibitors, prostaglandin inhibitors, or human chorionic gonadotropin) (19
trials, 1913 women). Similarly for the primary outcome of serious infant outcome,
there were no significant differences between the infants exposed to magnesium
sulphate and those not (whether placebo/no alternative tocolytic drug,
betamimetics, calcium channel blockers, cox inhibitors, prostaglandin inhibitors,
human chorionic gonadotropin or various tocolytic drugs) (18 trials; 2187
babies). No trials reported the outcome of extremely preterm birth. In the seven
trials that reported serious maternal outcomes, no events were recorded.In the
group treated with magnesium sulphate compared with women receiving antenatal
placebo or no alternative tocolytic drug, a borderline increased risk of total
death (fetal, neonatal, infant) was seen (risk ratio (RR) 4.56, 95% confidence
interval (CI) 1.00 to 20.86; two trials, 257 babies); none of the comparisons
between magnesium sulphate and other classes of tocolytic drugs showed
differences for this outcome (10 trials, 991 babies). The outcomes of neonatal
and/or infant deaths and of fetal deaths did not show differences between
magnesium sulphate and no magnesium sulphate, whether compared with placebo/no
alternative tocolytic drug, or any specific class of tocolytic drug. For most of
the other secondary outcomes, there were no significant differences between
magnesium sulphate and the control groups for risk of preterm birth (except for a
significantly lower risk with magnesium sulphate when compared with barbiturates
in one trial of 65 women), gestational age at birth, interval between trial entry
and birth, other neonatal morbidities, or neurodevelopmental outcomes. Duration
of neonatal intensive care unit stay was significantly increased in the magnesium
sulphate group compared with the calcium channel blocker group, but not when
compared with cox inhibitors or prostaglandin inhibitors. No maternal deaths were
reported in the four trials reporting this outcome. Significant differences
between magnesium sulphate and controls were not seen for maternal adverse events
severe enough to stop treatment, except for a significant benefit of magnesium
sulphate compared with betamimetics in a single trial. AUTHORS' CONCLUSIONS:
Magnesium sulphate is ineffective at delaying birth or preventing preterm birth,
has no apparent advantages for a range of neonatal and maternal outcomes as a
tocolytic agent and its use for this indication may be associated with an
increased risk of total fetal, neonatal or infant mortality (in contrast to its
use in appropriate groups of women for maternal, fetal, neonatal and infant
neuroprotection where beneficial effects have been demonstrated).
PMID- 25126774
TI - [Two forms of familial hypercholesterolemia: differences in cardiovascular risk
factors, cardiac and extracardiac atherosclerosis].
AB - BACKGROUND AND AIM: The monogenetic hypercholesterolemias (HC) are associated
with a very high risk of premature coronary heart disease (CHD). We sought to
assess the influence of the genetic defect and the cardiovascular risk factors on
the manifestation of atherosclerotic complications in two forms of genetic HC.
PATIENTS AND METHODS: Data of patients with genetically defined HC (54 LDL
receptor defective familial hypercholesterolemia (FH) and 54 familial defective
apolipoprotein B (FDB)) were analysed retrospectively for cardiac and
extracardiac atherosclerosis. RESULTS: Total and LDL-cholesterol were
significantly higher in FH men than in FDB men, but not so in women. 41.8% of FH
patients had CHD (mean age 41 years), 5.6% of FDB (mean age 52 years). Stenoses
(>50% narrowing) of the internal carotid artery were verified in 15% of FH and 4%
of FDB patients. Peripheral arterial disease was found in 3 FH and 2 FDB
patients. Hypertension and active smoking were allotted almost equally, body
weight was normal in most of the patients (BMI <= 25 kg/m(2)). Conlusion:
Patients with genetic HC suffer from early manifestation of cardiac disease.
Patients with FH seem to be affected more often than patients with FDB. Early
diagnosis and early and lifelong treatment are essential and, according to the
literature, lead to a delay of disease manifestation.
PMID- 25126775
TI - Fish population studies using parasites from the Southeastern Pacific Ocean:
considering host population changes and species body size as sources of
variability of parasite communities.
AB - Research using parasites in fish population studies in the South Eastern Pacific
(SEP) is summarized. There are 27 such studies (snapshots mainly) in single host
species sampled at different geographic localities and at somewhat similar times.
They have been devoted mainly to economically important species, though others on
coastal and intertidal fish or on less- or non-commercial species provide
insights on scales of temporal and spatial variation of parasite
infracommunities. Later, we assess whether the probability of harbouring
parasites depends on the host species body size. Our results indicate that a
stronger tool for fish population studies may be developed under regular (long
term) scrutiny of parasite communities, especially of small fish host species,
due to their larger variability in richness, abundance and total biomass, than in
large fish species. Finally, it might also be necessary to consider the effects
of fishing on parasite communities as well as the natural oscillations (coupled
or not) of host and parasite populations.
PMID- 25126776
TI - Hippo pathway key to ploidy checkpoint.
AB - Tetraploid cells generated by abnormal cell division are often arrested during
the cell cycle or cleared by apoptosis. Evasion of these defense mechanisms leads
to genomic instability and tumorigenesis. In this issue, Ganem et al. report that
extra centrosome-induced activation of the Hippo pathway kinase LATS2 is a key
mechanism of tetraploidy-induced cell-cycle arrest.
PMID- 25126777
TI - A timeless but timely connection between replication and recombination.
AB - Initiation of meiotic recombination by DNA double-strand break formation is
temporally coordinated with replication. Murakami and Keeney show that this
coordination requires recruitment of the Dbf4-dependent kinase to the replication
fork by the conserved TIM-TIPIN complex. The same mechanism may regulate other
important replication-associated processes.
PMID- 25126778
TI - CellNet--where your cells are standing.
AB - The manufacturing of clinically relevant cells is a widely used strategy in
regenerative medicine. Cahan et al. develop a network biology platform named
CellNet to accurately assess the fidelity of such cells and spot aberrant
regulatory networks, and Morris et al. apply this platform to improve cell
manufacturing.
PMID- 25126779
TI - Lights, X-rays, oxygen!
AB - Photosystem II uses metal ions to oxidize water to form O2. Two recent papers
employ the new technique of serial femtosecond crystallography utilizing X-ray
free-electron lasers and nanocrystals to obtain initial structures of
intermediate states of photosystem II catalysis at the site of oxygen production.
PMID- 25126781
TI - Phenotypic variation of Salmonella in host tissues delays eradication by
antimicrobial chemotherapy.
AB - Antibiotic therapy often fails to eliminate a fraction of transiently refractory
bacteria, causing relapses and chronic infections. Multiple mechanisms can induce
such persisters with high antimicrobial tolerance in vitro, but their in vivo
relevance remains unclear. Using a fluorescent growth rate reporter, we detected
extensive phenotypic variation of Salmonella in host tissues. This included slow
growing subsets as well as well-nourished fast-growing subsets driving disease
progression. Monitoring of Salmonella growth and survival during chemotherapy
revealed that antibiotic killing correlated with single-cell division rates.
Nondividing Salmonella survived best but were rare, limiting their impact.
Instead, most survivors originated from abundant moderately growing, partially
tolerant Salmonella. These data demonstrate that host tissues diversify pathogen
physiology, with major consequences for disease progression and control.
PMID- 25126780
TI - Altering the intestinal microbiota during a critical developmental window has
lasting metabolic consequences.
AB - Acquisition of the intestinal microbiota begins at birth, and a stable microbial
community develops from a succession of key organisms. Disruption of the
microbiota during maturation by low-dose antibiotic exposure can alter host
metabolism and adiposity. We now show that low-dose penicillin (LDP), delivered
from birth, induces metabolic alterations and affects ileal expression of genes
involved in immunity. LDP that is limited to early life transiently perturbs the
microbiota, which is sufficient to induce sustained effects on body composition,
indicating that microbiota interactions in infancy may be critical determinants
of long-term host metabolic effects. In addition, LDP enhances the effect of high
fat diet induced obesity. The growth promotion phenotype is transferrable to germ
free hosts by LDP-selected microbiota, showing that the altered microbiota, not
antibiotics per se, play a causal role. These studies characterize important
variables in early-life microbe-host metabolic interaction and identify several
taxa consistently linked with metabolic alterations. PAPERCLIP:
PMID- 25126782
TI - Function of a Foxp3 cis-element in protecting regulatory T cell identity.
AB - The homeostasis of multicellular organisms requires terminally differentiated
cells to preserve their lineage specificity. However, it is unclear whether
mechanisms exist to actively protect cell identity in response to environmental
cues that confer functional plasticity. Regulatory T (Treg) cells, specified by
the transcription factor Foxp3, are indispensable for immune system homeostasis.
Here, we report that conserved noncoding sequence 2 (CNS2), a CpG-rich Foxp3
intronic cis-element specifically demethylated in mature Tregs, helps maintain
immune homeostasis and limit autoimmune disease development by protecting Treg
identity in response to signals that shape mature Treg functions and drive their
initial differentiation. In activated Tregs, CNS2 helps protect Foxp3 expression
from destabilizing cytokine conditions by sensing TCR/NFAT activation, which
facilitates the interaction between CNS2 and Foxp3 promoter. Thus, epigenetically
marked cis-elements can protect cell identity by sensing key environmental cues
central to both cell identity formation and functional plasticity without
interfering with initial cell differentiation.
PMID- 25126783
TI - Control of the inheritance of regulatory T cell identity by a cis element in the
Foxp3 locus.
AB - In multicellular organisms, specialized functions are delegated to distinct cell
types whose identity and functional integrity are maintained upon challenge.
However, little is known about the mechanisms enabling lineage inheritance and
their biological implications. Regulatory T (Treg) cells, which express the
transcription factor Foxp3, suppress fatal autoimmunity throughout the lifespan
of animals. Here, we show that a dedicated Foxp3 intronic element CNS2 maintains
Treg cell lineage identity by acting as a sensor of the essential Treg cell
growth factor IL-2 and its downstream target STAT5. CNS2 sustains Foxp3
expression during division of mature Treg cells when IL-2 is limiting and
counteracts proinflammatory cytokine signaling that leads to the loss of Foxp3.
CNS2-mediated stable inheritance of Foxp3 expression is critical for adequate
suppression of diverse types of chronic inflammation by Treg cells and prevents
their differentiation into inflammatory effector cells. The described mechanism
may represent a general principle of the inheritance of differentiated cell
states.
PMID- 25126785
TI - Type II cadherins guide assembly of a direction-selective retinal circuit.
AB - Complex retinal circuits process visual information and deliver it to the brain.
Few molecular determinants of synaptic specificity in this system are known.
Using genetic and optogenetic methods, we identified two types of bipolar
interneurons that convey visual input from photoreceptors to a circuit that
computes the direction in which objects are moving. We then sought recognition
molecules that promote selective connections of these cells with previously
characterized components of the circuit. We found that the type II cadherins,
cdh8 and cdh9, are each expressed selectively by one of the two bipolar cell
types. Using loss- and gain-of-function methods, we showed that they are critical
determinants of connectivity in this circuit and that perturbation of their
expression leads to distinct defects in visually evoked responses. Our results
reveal cellular components of a retinal circuit and demonstrate roles of type II
cadherins in synaptic choice and circuit function.
PMID- 25126784
TI - Stem-loop recognition by DDX17 facilitates miRNA processing and antiviral
defense.
AB - DEAD-box helicases play essential roles in RNA metabolism across species, but
emerging data suggest that they have additional functions in immunity. Through
RNAi screening, we identify an evolutionarily conserved and interferon
independent role for the DEAD-box helicase DDX17 in restricting Rift Valley fever
virus (RVFV), a mosquito-transmitted virus in the bunyavirus family that causes
severe morbidity and mortality in humans and livestock. Loss of Drosophila DDX17
(Rm62) in cells and flies enhanced RVFV infection. Similarly, depletion of DDX17
but not the related helicase DDX5 increased RVFV replication in human cells.
Using crosslinking immunoprecipitation high-throughput sequencing (CLIP-seq), we
show that DDX17 binds the stem loops of host pri-miRNA to facilitate their
processing and also an essential stem loop in bunyaviral RNA to restrict
infection. Thus, DDX17 has dual roles in the recognition of stem loops: in the
nucleus for endogenous microRNA (miRNA) biogenesis and in the cytoplasm for
surveillance against structured non-self-elements.
PMID- 25126786
TI - State-dependent architecture of thalamic reticular subnetworks.
AB - Behavioral state is known to influence interactions between thalamus and cortex,
which are important for sensation, action, and cognition. The thalamic reticular
nucleus (TRN) is hypothesized to regulate thalamo-cortical interactions, but the
underlying functional architecture of this process and its state dependence are
unknown. By combining the first TRN ensemble recording with psychophysics and
connectivity-based optogenetic tagging, we found reticular circuits to be
composed of distinct subnetworks. While activity of limbic-projecting TRN neurons
positively correlates with arousal, sensory-projecting neurons participate in
spindles and show elevated synchrony by slow waves during sleep. Sensory
projecting neurons are suppressed by attentional states, demonstrating that their
gating of thalamo-cortical interactions is matched to behavioral state.
Bidirectional manipulation of attentional performance was achieved through
subnetwork-specific optogenetic stimulation. Together, our findings provide
evidence for differential inhibition of thalamic nuclei across brain states,
where the TRN separately controls external sensory and internal limbic processing
facilitating normal cognitive function. PAPERFLICK:
PMID- 25126787
TI - Probing the stochastic, motor-driven properties of the cytoplasm using force
spectrum microscopy.
AB - Molecular motors in cells typically produce highly directed motion; however, the
aggregate, incoherent effect of all active processes also creates randomly
fluctuating forces, which drive diffusive-like, nonthermal motion. Here, we
introduce force-spectrum-microscopy (FSM) to directly quantify random forces
within the cytoplasm of cells and thereby probe stochastic motor activity. This
technique combines measurements of the random motion of probe particles with
independent micromechanical measurements of the cytoplasm to quantify the
spectrum of force fluctuations. Using FSM, we show that force fluctuations
substantially enhance intracellular movement of small and large components. The
fluctuations are three times larger in malignant cells than in their benign
counterparts. We further demonstrate that vimentin acts globally to anchor
organelles against randomly fluctuating forces in the cytoplasm, with no effect
on their magnitude. Thus, FSM has broad applications for understanding the
cytoplasm and its intracellular processes in relation to cell physiology in
healthy and diseased states.
PMID- 25126788
TI - Cytokinesis failure triggers hippo tumor suppressor pathway activation.
AB - Genetically unstable tetraploid cells can promote tumorigenesis. Recent estimates
suggest that ~37% of human tumors have undergone a genome-doubling event during
their development. This potentially oncogenic effect of tetraploidy is countered
by a p53-dependent barrier to proliferation. However, the cellular defects and
corresponding signaling pathways that trigger growth suppression in tetraploid
cells are not known. Here, we combine RNAi screening and in vitro evolution
approaches to demonstrate that cytokinesis failure activates the Hippo tumor
suppressor pathway in cultured cells, as well as in naturally occurring
tetraploid cells in vivo. Induction of the Hippo pathway is triggered in part by
extra centrosomes, which alter small G protein signaling and activate LATS2
kinase. LATS2 in turn stabilizes p53 and inhibits the transcriptional regulators
YAP and TAZ. These findings define an important tumor suppression mechanism and
uncover adaptive mechanisms potentially available to nascent tumor cells that
bypass this inhibitory regulation.
PMID- 25126789
TI - Reactivation of developmentally silenced globin genes by forced chromatin
looping.
AB - Distal enhancers commonly contact target promoters via chromatin looping. In
erythroid cells, the locus control region (LCR) contacts beta-type globin genes
in a developmental stage-specific manner to stimulate transcription. Previously,
we induced LCR-promoter looping by tethering the self-association domain (SA) of
Ldb1 to the beta-globin promoter via artificial zinc fingers. Here, we show that
targeting the SA to a developmentally silenced embryonic globin gene in adult
murine erythroblasts triggers its transcriptional reactivation. This activity
depends on the LCR, consistent with an LCR-promoter looping mechanism.
Strikingly, targeting the SA to the fetal gamma-globin promoter in primary adult
human erythroblasts increases gamma-globin promoter-LCR contacts, stimulating
transcription to approximately 85% of total beta-globin synthesis, with a
reciprocal reduction in adult beta-globin expression. Our findings demonstrate
that forced chromatin looping can override a stringent developmental gene
expression program and suggest a novel approach to control the balance of globin
gene transcription for therapeutic applications.
PMID- 25126790
TI - Temporospatial coordination of meiotic DNA replication and recombination via DDK
recruitment to replisomes.
AB - It has been long appreciated that, during meiosis, DNA replication is coordinated
with the subsequent formation of the double-strand breaks (DSBs) that initiate
recombination, but a mechanistic understanding of this process was elusive. We
now show that, in yeast, the replisome-associated components Tof1 and Csm3
physically associate with the Dbf4-dependent Cdc7 kinase (DDK) and recruit it to
the replisome, where it phosphorylates the DSB-promoting factor Mer2 in the wake
of the replication fork, synchronizing replication with an early prerequisite for
DSB formation. Recruiting regulatory kinases to replisomes may be a general
mechanism to ensure spatial and temporal coordination of replication with other
chromosomal processes.
PMID- 25126791
TI - Ecdysone and mediator change energy metabolism to terminate proliferation in
Drosophila neural stem cells.
AB - Stem cells are highly abundant during early development but become a rare
population in most adult organs. The molecular mechanisms causing stem cells to
exit proliferation at a specific time are not well understood. Here, we show that
changes in energy metabolism induced by the steroid hormone ecdysone and the
Mediator initiate an irreversible cascade of events leading to cell-cycle exit in
Drosophila neural stem cells. We show that the timely induction of oxidative
phosphorylation and the mitochondrial respiratory chain are required in
neuroblasts to uncouple the cell cycle from cell growth. This results in a
progressive reduction in neuroblast cell size and ultimately in terminal
differentiation. Brain tumor mutant neuroblasts fail to undergo this shrinkage
process and continue to proliferate until adulthood. Our findings show that cell
size control can be modified by systemic hormonal signaling and reveal a unique
connection between metabolism and proliferation in stem cells.
PMID- 25126792
TI - Dissecting engineered cell types and enhancing cell fate conversion via CellNet.
AB - Engineering clinically relevant cells in vitro holds promise for regenerative
medicine, but most protocols fail to faithfully recapitulate target cell
properties. To address this, we developed CellNet, a network biology platform
that determines whether engineered cells are equivalent to their target tissues,
diagnoses aberrant gene regulatory networks, and prioritizes candidate
transcriptional regulators to enhance engineered conversions. Using CellNet, we
improved B cell to macrophage conversion, transcriptionally and functionally, by
knocking down predicted B cell regulators. Analyzing conversion of fibroblasts to
induced hepatocytes (iHeps), CellNet revealed an unexpected intestinal program
regulated by the master regulator Cdx2. We observed long-term functional
engraftment of mouse colon by iHeps, thereby establishing their broader potential
as endoderm progenitors and demonstrating direct conversion of fibroblasts into
intestinal epithelium. Our studies illustrate how CellNet can be employed to
improve direct conversion and to uncover unappreciated properties of engineered
cells.
PMID- 25126793
TI - CellNet: network biology applied to stem cell engineering.
AB - Somatic cell reprogramming, directed differentiation of pluripotent stem cells,
and direct conversions between differentiated cell lineages represent powerful
approaches to engineer cells for research and regenerative medicine. We have
developed CellNet, a network biology platform that more accurately assesses the
fidelity of cellular engineering than existing methodologies and generates
hypotheses for improving cell derivations. Analyzing expression data from 56
published reports, we found that cells derived via directed differentiation more
closely resemble their in vivo counterparts than products of direct conversion,
as reflected by the establishment of target cell-type gene regulatory networks
(GRNs). Furthermore, we discovered that directly converted cells fail to
adequately silence expression programs of the starting population and that the
establishment of unintended GRNs is common to virtually every cellular
engineering paradigm. CellNet provides a platform for quantifying how closely
engineered cell populations resemble their target cell type and a rational
strategy to guide enhanced cellular engineering.
PMID- 25126796
TI - Severe sepsis outcomes: how are we doing?*.
PMID- 25126797
TI - Who decides who should benefit? Allocating critical care in the context of
"futile treatment"*.
PMID- 25126798
TI - Why knowing the effects of positive-pressure ventilation on venous, pleural, and
pericardial pressures is important to the bedside clinician?*.
PMID- 25126794
TI - Supergenomic network compression and the discovery of EXP1 as a glutathione
transferase inhibited by artesunate.
AB - A central problem in biology is to identify gene function. One approach is to
infer function in large supergenomic networks of interactions and ancestral
relationships among genes; however, their analysis can be computationally
prohibitive. We show here that these biological networks are compressible. They
can be shrunk dramatically by eliminating redundant evolutionary relationships,
and this process is efficient because in these networks the number of
compressible elements rises linearly rather than exponentially as in other
complex networks. Compression enables global network analysis to computationally
harness hundreds of interconnected genomes and to produce functional predictions.
As a demonstration, we show that the essential, but functionally uncharacterized
Plasmodium falciparum antigen EXP1 is a membrane glutathione S-transferase. EXP1
efficiently degrades cytotoxic hematin, is potently inhibited by artesunate, and
is associated with artesunate metabolism and susceptibility in drug-pressured
malaria parasites. These data implicate EXP1 in the mode of action of a frontline
antimalarial drug.
PMID- 25126799
TI - The valuable contribution of spiritual care to end-of-life care in the ICU*.
PMID- 25126800
TI - It's not "do" but "why do" rapid response systems work?*.
PMID- 25126801
TI - From storm to suppression in sepsis: are bands the link?*.
PMID- 25126802
TI - Biomarkers to detect sepsis: a "burning" issue but still a long way to go*.
PMID- 25126803
TI - Why do-not-resuscitate orders matter in comparative effectiveness research*.
PMID- 25126804
TI - Anemia in the critically ill: do we need to live with it?*.
PMID- 25126805
TI - Acute kidney injury after cardiac surgery: the injury that keeps on hurting?*.
PMID- 25126806
TI - "The rhythm is gonna get you...": extracorporeal membrane oxygenation with and
without intra-aortic balloon pumps*.
PMID- 25126807
TI - Does the reperfusing brain recover better under pressure?*.
PMID- 25126808
TI - Death in the ICU: when comfort is therapeutic*.
PMID- 25126809
TI - Clearing lactate is clearly better...but how much?*.
PMID- 25126810
TI - The impact of possible clonal spread of Acinetobacter baumannii complex
bacteremia.
PMID- 25126811
TI - The authors reply.
PMID- 25126812
TI - What is the impact of catheter removal on the outcome of non-catheter-related
candidemia?
PMID- 25126813
TI - The authors reply.
PMID- 25126814
TI - Conservative oxygen therapy in mechanically ventilated patients.
PMID- 25126815
TI - The authors reply.
PMID- 25126816
TI - Is the revised cardiac risk index the right risk index for vascular surgery
patients?
PMID- 25126817
TI - The authors reply.
PMID- 25126818
TI - Mitochondrial respiration and passive stretch of the diaphragm during unilateral
phrenic nerve stimulation.
PMID- 25126819
TI - The authors reply.
PMID- 25126820
TI - From targeting to optimizing cerebral perfusion pressure.
PMID- 25126821
TI - The authors reply.
PMID- 25126822
TI - Time to declare a moratorium on stress ulcer prophylaxis in critically ill.
PMID- 25126823
TI - The authors reply.
PMID- 25126824
TI - Mutation strategies for obtaining chitooligosaccharides with longer chains by
transglycosylation reaction of family GH18 chitinase.
AB - Enhancing the transglycosylation (TG) activity of glycoside hydrolases does not
always result in the production of oligosaccharides with longer chains, because
the TG products are often decomposed into shorter oligosaccharides. Here, we
investigated the mutation strategies for obtaining chitooligosaccharides with
longer chains by means of TG reaction catalyzed by family GH18 chitinase A from
Vibrio harveyi (VhChiA). HPLC analysis of the TG products from incubation of
chitooligosaccharide substrates, GlcNAc(n), with several mutant VhChiAs suggested
that mutant W570G (mutation of Trp570 to Gly) and mutant D392N (mutation of
Asp392 to Asn) significantly enhanced TG activity, but the TG products were
immediately hydrolyzed into shorter GlcNAc(n). On the other hand, the TG products
obtained from mutants D313A and D313N (mutations of Asp313 to Ala and Asn,
respectively) were not further hydrolyzed, leading to the accumulation of
oligosaccharides with longer chains. The data obtained from the mutant VhChiAs
suggested that mutations of Asp313, the middle aspartic acid residue of the DxDxE
catalytic motif, to Ala and Asn are most effective for obtaining
chitooligosaccharides with longer chains.
PMID- 25126825
TI - Explaining women's high satisfaction with objectively poor quality childbirth
services: Armenia as a case study.
AB - Despite documented low-quality care in Armenia, surveys document high ratings of
patient satisfaction with health care services. We explored reasons for high
satisfaction in Armenia despite poor quality. Twenty-five women who recently
delivered participated in this qualitative study through in-depth interviews.
Patients avoided critiquing health care services because of personal
relationships with and respect for providers and fear of losing services.
Although they shared an understanding of what quality care should be, many were
satisfied because their low expectations were met. Further mixed methods research
may explain this dissonance. Until then, patient satisfaction measures need
careful, contextual interpretations.
PMID- 25126826
TI - Changes in markers of brain serotonin activity in response to chronic exercise in
senior men.
AB - Aging is associated with noticeable impairments in brain serotonin transmission,
which might contribute to increased vulnerability to developing depression in
later life. Animal and human studies have shown that aerobic exercise can
stimulate brain serotonin activity and trigger parallel elevations in tryptophan
(TRP, the serotonin precursor) availability in blood plasma. However, the
influence of chronic exercise on serotonergic activity in older adults is not yet
known. Sixteen men aged 64 +/- 3 years exercised for 1 h (67%-70% peak oxygen
consumption) at baseline and following 16 weeks of aerobic training. The main
outcome measures were cardiorespiratory fitness, body composition, branched-chain
amino acids (BCAA), TRP, prolactin, lactate, and free fatty acids (FFA). Changes
in plasma free-TRP/BCAA and prolactin served as surrogates for TRP availability
and serotonin activity, respectively. Chronic exercise decreased body mass (P <
0.05) whilst it increased ventilatory threshold 2 (P < 0.01). Although training
did not affect plasma TRP availability to the brain at rest, both pre- and post
training exercise challenges markedly increased TRP availability (P < 0.001). The
free-TRP/BCAA values reached a ceiling during exercise that was lower following
training (P < 0.05), whereas similar patterns were found for prolactin, lactate,
and FFA. These data show that aerobic exercise elicits consistent transient
elevations in plasma TRP availability to the brain in older men; the elevations
were independent from physical training, although less pronounced following
training. The data support the contention that repeated elevations in brain
serotonin activity might be involved in the antidepressant effect of exercise
training in older adults.
PMID- 25126827
TI - Functional interleukin-21 polymorphism is a protective factor of diffuse large B
cell lymphoma.
AB - Interleukin-21 (IL-21) is a recently discovered cytokine and plays critical roles
in antitumor immune responses. Diffuse large B-cell lymphoma (DLBCL) is the most
common type of non-Hodgkin lymphoma. In this study, we investigated the
association between IL-21 genetic polymorphisms and the susceptibility to DLBCL,
and the possible functions of these polymorphisms. Two IL-21 polymorphisms,
rs907715G/A and rs2221903A/G, were examined in 212 DLBCL patients and 232 healthy
controls. Data showed that percentages of rs907715GA and AA genotypes were
significantly lower in patients than in controls (odds ratio [OR]=0.60, 95%
confidence interval [CI]: 0.40-0.90, p=0.014; OR=0.31, 95% CI: 0.17-0.56,
p<0.001, respectively). Frequency of the rs2221903A/G polymorphism did not reveal
any significant differences between patients and healthy donors. Further analyses
demonstrated a significantly decreased number of rs907715AA genotype in patients
with advanced Ann Arbor stages (III+IV). Moreover, we investigated the
correlation between IL-21 polymorphisms and serum level of IL-21. Results showed
that subjects carrying rs907715AA had significantly increased level of IL-21 than
those with GG genotype or GA genotype. These data suggest that rs907715G/A
polymorphism may act as a protective factor of DLBCL and might affect the serum
level of IL-21.
PMID- 25126828
TI - Nocardia farcinica brain abscess: epidemiology, pathophysiology, and literature
review.
AB - BACKGROUND: Infections caused by Nocardia farcinica are potentially lethal
because of the organism's tendency to disseminate and resist antibiotics. Central
nervous system involvement has been documented in 30% of infections caused N.
farcinica. METHODS: Case report and review of the literature. RESULTS: A case of
primary brain abscess caused by N. farcinica, identified by 16SrRNA sequencing,
is presented, and 39 cases reported previously in the literature are reviewed.
Our patient underwent a neuronavigation-guided right frontal craniotomy and was
treated with trimethoprim/sulfamethoxazole and amoxicillin-clavulanic acid for 12
mo. He showed marginal improvement in his prior left hemiparesis at the last
review 14 months later. CONCLUSION: Cases of N. farcinica infections are being
reported increasingly because of recent changes in taxonomy and diagnostic
methodology. This change in epidemiology has implications for therapy because of
the organism's pathogenicity and natural resistance to multiple antimicrobial
agents, including third-generation cephalosporins. Any delay in starting
appropriate antibiotic therapy can have adverse consequences.
PMID- 25126829
TI - Transnationals' experience of dying in their adopted country: a systematic
review.
AB - BACKGROUND: Social and emotional challenges of migration and integration include
managing memories and perceptions of country of birth, leaving loved relatives
behind, and the challenges of maintaining traditions, such as cultural food and
practices. For many migrants, the strong connection with their birth country is
never completely severed, which may become pertinent at particular events and
stages in life with inherent emotional impact. This may be particularly the case
for end-of-life experience. OBJECTIVE: We undertook a systematic review of
published evidence of research to identify the lived experience of migrants dying
in a country different from their country of birth. DESIGN: The search terms
[transnationals OR migran* OR immigran*] AND [emotions OR belonging OR
acculturation OR national identity] AND [dying OR end-of-life OR contemplation of
dying] AND [palliative care OR terminal care] were used on the following
electronic databases: MEDLINE, Embase, CINAHL, EBSCO, Geobase, PsychINFO, and
Scopus to the end date of January 2014. No date limit was imposed. All research
methodologies were included. The search was restricted to human subjects and
English language. RESULTS: Seven qualitative studies met the criteria. Thematic
analysis of these studies identified three main themes: sense of dual identity,
importance of traditions from their country of origin, and dying preferences.
CONCLUSION: Findings have implications for the provision of palliative end-of
life care for dying transnationals, particularly in relation to providing support
for migrants who are dying to resolve social and emotional issues.
PMID- 25126831
TI - Development and evaluation of ITS- and aflP-based LAMP assays for rapid detection
of Aspergillus flavus in food samples.
AB - Aspergillus flavus is a common filamentous fungus that produces aflatoxins and
presents a major threat to agriculture and human health. Previous studies focused
mainly on the detection of A. flavus or aflatoxin separately. Here, we developed
internal transcribed spacer (ITS)- and aflP-based rapid detection of A. flavus in
food samples using the loop-mediated isothermal amplification (LAMP) method. The
ITS1-5.8S-ITS2 rDNA region of A. flavus and the aflatoxin-encoding gene aflP were
used as target regions. The detection limits of A. flavus and aflP were 10 fg and
1 pg pure DNA, respectively, which allows aflatoxin-contaminated samples to be
differentiated from infected samples and reduces false-negative or false-positive
results. For specificity testing, DNA extracted from 7 A. flavus, 5 different
Aspergillus spp., and 21 other fungi were used, and our results showed that A.
flavus strains are detected by ITS-based detection and aflatoxigenic A. flavus
strains are detected by aflP-based detection. Furthermore, the ITS- and aflP
based LAMP assays were used for detection analysis of DNA from food samples
artificially and naturally contaminated with A. flavus. Our results showed that
the detection rate of A. flavus based on the multi-ITS-based LAMP detection is
100% and that the aflatoxigenic strains in all A. flavus are detected by the aflP
based LAMP assay. The LAMP protocol described in our study represents a rapid and
highly specific and sensitive diagnostic method for A. flavus detection, which
can be used as a diagnostic tool that simplifies A. flavus monitoring and
guarantees the quality and safety of foods.
PMID- 25126832
TI - Plasmonic Ag@AgCl nanotubes fabricated from copper nanowires as high-performance
visible light photocatalyst.
AB - In this paper, plasmonic photocatalyst Ag@AgCl nanotubes were prepared by a cost
efficient and template-based method and their photocatalytic properties were
studied. In the synthesis, copper nanowires were first synthesized and Ag
nanotubes were then obtained through the galvanic reaction between copper and Ag
ions. The formation of Ag@AgCl nanotubes was finally achieved by in situ
oxidation reaction upon the addition of FeCl3. The crystal structure of the
product was characterized by X-ray powder diffraction. The morphology and
composition of the composite were studied by scanning electron microscopy,
transmission electron microscopy, and X-ray photoelectron spectroscopy
measurements. All the structure characterizations showed that the tubulate
product was produced by the synthetic processes. By using the obtained product as
photocatalyst, the photodegradation of methyl orange (MO) was investigated under
visible light. The experimental results showed that the as-prepared Ag@AgCl
nanotubes exhibit excellent photocatalytic performance and high stability. Under
visible light irradiation, more than 92.58% of the MO dye has been decomposed in
10 min on the product with a 1:1 ratio of Fe/Ag. On the basis of the proposed
mechanism, the improved photocatalytic activities of the Ag@AgCl hybrids can be
ascribed to the enhanced surface area for dye molecule adsorption, enhanced
visible light absorbance, and the efficient charge separation of the hybrid
nanostructures.
PMID- 25126830
TI - Executive function late effects in survivors of pediatric brain tumors and acute
lymphoblastic leukemia.
AB - BACKGROUND: Survivors of pediatric brain tumors (BT) and acute lymphoblastic
leukemia (ALL) are at risk for neurocognitive late effects related to executive
function. PROCEDURE: Survivors of BT (48) and ALL (50) completed neurocognitive
assessment. Executive function was compared to estimated IQ and population norms
by diagnostic group. RESULTS: Both BT and ALL demonstrated relative executive
function weaknesses. As a group, BT survivors demonstrated weaker executive
functioning than expected for age. Those BT survivors with deficits exhibited a
profile suggestive of global executive dysfunction, while affected ALL survivors
tended to demonstrate specific rapid naming deficits. CONCLUSION: Findings
suggest that pediatric BT and ALL survivors may exhibit different profiles of
executive function late effects, which may necessitate distinct intervention
plans.
PMID- 25126834
TI - Enhancing photoinduced electron transfer efficiency of fluorescent pH-probes with
halogenated phenols.
AB - Photoinduced electron transfer (PET), which causes pH-dependent quenching of
fluorescent dyes, is more effectively introduced by phenolic groups than by amino
groups which have been much more commonly used so far. That is demonstrated by
fluorescence measurements involving several classes of fluorophores.
Electrochemical measurements show that PET in several amino-modified dyes is
thermodynamically favorable, even though it was not experimentally found,
underlining the importance of kinetic aspects to the process. Consequently, the
attachment of phenolic groups allows for fast and simple preparation of a wide
selection of fluorescent pH-probes with tailor-made spectral properties,
sensitive ranges, and individual advantages, so that a large number of
applications can be realized. Fluorophores carrying phenolic groups may also be
used for sensing analytes other than pH or molecular switching and signaling.
PMID- 25126835
TI - Inhibition of protein and cell attachment on materials generated from N-(2
hydroxypropyl) acrylamide.
AB - Effective control over biointerfacial interactions is essential for a broad range
of biomedical applications. At this point in time, only a relatively small range
of radically polymerizable monomers have been described that are able to generate
low fouling polymer materials and surfaces. The most important examples that have
been successfully used in the context of the reduction of nonspecific protein
adsorption and subsequent cell attachment include PEG-based monomers such as
poly(ethylene glycol) methacrylate (PEGMA), zwitterionic monomers such as 2
methacryloyloxyethyl phosphorylcholine and noncharged monomers such as acrylamide
and N-(2-hydroxypropyl) methacrylamide (HPMAm). However, issues such as oxidative
degradation and poor polymerization characteristics limit the applicability of
most of these candidates. Here we have synthesized the monomer N-(2
hydroxypropyl) acrylamide (HPAm), examined its polymerization kinetics and
evaluated its suitability for RAFT mediated polymerization in comparison to
HPMAm. We also synthesized hydrogels using HPMAm and HPAm and evaluated the
ability of HPAm polymers to occlude protein adsorption and cell attachment. In
RAFT-controlled polymerization, much faster (8*) polymerization was observed for
HPAm relative to HPMAm and better control was achieved over the molecular weight
distribution. The performance of hydrogels prepared from HPAm in the prevention
of protein adsorption and cellular attachment was equivalent to or better than
that observed for materials made from HPMAm and PEG. These results open the door
for HPAm based polymers in applications where effective control over
biointerfacial interactions is required.
PMID- 25126836
TI - Chiral phosphoric acid catalyzed highly enantioselective desymmetrization of 2
substituted and 2,2-disubstituted 1,3-diols via oxidative cleavage of benzylidene
acetals.
AB - A highly enantioselective catalytic protocol for the desymmetrization of a wide
variety of 2-substituted and 2,2-disubstituted 1,3-diols is reported. This
reaction proceeds through the formation of an "ortho ester" intermediate via
oxidation of 1,3-diol benzylidene acetal by dimethyldioxirane (DMDO) and the
subsequent proton transfer catalyzed by chiral phosphoric acid (CPA). The
mechanism and origins of enantioselectivity of this reaction are identified using
DFT calculations. The oxidation by DMDO is rate-determining, and the phosphoric
acid significantly accelerates the proton transfer; the attractive interactions
between the benzylidene part of the substrate and the 2,4,6-triisopropyl group of
CPA are the key to high enantioselectivity.
PMID- 25126833
TI - Design, synthesis, and structure-activity relationship studies of a series of [4
(4-carboxamidobutyl)]-1-arylpiperazines: insights into structural features
contributing to dopamine D3 versus D2 receptor subtype selectivity.
AB - Antagonist and partial agonist modulators of the dopamine D3 receptor (D3R) have
emerged as promising therapeutics for the treatment of substance abuse and
neuropsychiatric disorders. However, development of druglike lead compounds with
selectivity for the D3 receptor has been challenging because of the high sequence
homology between the D3R and the dopamine D2 receptor (D2R). In this effort, we
synthesized a series of acylaminobutylpiperazines incorporating aza-aromatic
units and evaluated their binding and functional activities at the D3 and D2
receptors. Docking studies and results from evaluations against a set of chimeric
and mutant receptors suggest that interactions at the extracellular end of TM7
contribute to the D3R versus D2R selectivity of these ligands. Molecular insights
from this study could potentially enable rational design of potent and selective
D3R ligands.
PMID- 25126837
TI - Solution speciation of plutonium and Americium at an Australian legacy
radioactive waste disposal site.
AB - During the 1960s, radioactive waste containing small amounts of plutonium (Pu)
and americium (Am) was disposed in shallow trenches at the Little Forest Burial
Ground (LFBG), located near the southern suburbs of Sydney, Australia. Because of
periodic saturation and overflowing of the former disposal trenches, Pu and Am
have been transferred from the buried wastes into the surrounding surface soils.
The presence of readily detected amounts of Pu and Am in the trench waters
provides a unique opportunity to study their aqueous speciation under
environmentally relevant conditions. This study aims to comprehensively
investigate the chemical speciation of Pu and Am in the trench water by combining
fluoride coprecipitation, solvent extraction, particle size fractionation, and
thermochemical modeling. The predominant oxidation states of dissolved Pu and Am
species were found to be Pu(IV) and Am(III), and large proportions of both
actinides (Pu, 97.7%; Am, 86.8%) were associated with mobile colloids in the
submicron size range. On the basis of this information, possible management
options are assessed.
PMID- 25126838
TI - Cyclodextrins and surfactants in aqueous solution above the critical micelle
concentration: where are the cyclodextrins located?
AB - Cyclodextrins (CDs) are known to bind surfactant molecules below the surfactant
critical micelle concentration (CMC); however, interactions of CDs with
surfactant micelles (above the CMC) are not well understood. In particular,
direct structural evidence of the location of CDs in the different subphases
found in micellar solutions is lacking. We have utilized small-angle neutron
scattering (SANS) with contrast matching to probe the localization of alpha
cyclodextrin (alpha-CD) and 2-hydroxypropyl-beta-cyclodextrin (HPbeta-CD) in
sodium dodecyl sulfate (SDS) micelles in aqueous (D2O) solutions. SANS data from
solutions containing either hydrogenated or deuterated surfactants were analyzed
by considering three different scenarios pertaining to the localization of
cyclodextrin, either all in solution or some in the micelle shell or some in the
micelle core, and were simultaneously fitted using the core-shell prolate
ellipsoid form factor and the Hansen-Hayter-based structure factor. The scenario
that considered a fraction of CD to localize in the micelle core well described
the SANS data from both hydrogenated and deuterated SDS-CD-D2O solutions, while
the other two scenarios did not. Among the various structural and interaction
parameters obtained from this analysis, it emerged that the micelle core
consisted of up to ~10% HPbeta-CD or ~16% alpha-CD with respect to the total
number of molecules (surfactants and CDs) present in the micelle at 25 mM SDS,
and up to 14% HPbeta-CD or 28% alpha-CD at 50 mM SDS. This is the first study
that provides direct evidence on the location of cyclodextrin in the core of
surfactant micelles. An improved understanding of CD interactions with
surfactants and lipids would enable better strategies for drug encapsulation and
delivery with CDs.
PMID- 25126839
TI - Incidence and trends of blastomycosis-associated hospitalizations in the United
States.
AB - We used the State Inpatient Databases from the United States Agency for
Healthcare Research and Quality to provide state-specific age-adjusted
blastomycosis-associated hospitalization incidence throughout the entire United
States. Among the 46 states studied, states within the Mississippi and Ohio River
valleys had the highest age-adjusted hospitalization incidence. Specifically,
Wisconsin had the highest age-adjusted hospitalization incidence (2.9
hospitalizations per 100,000 person-years). Trends were studied in the five
highest hospitalization incidence states. From 2000 to 2011, blastomycosis
associated hospitalizations increased significantly in Illinois and Kentucky with
an average annual increase of 4.4% and 8.4%, respectively. Trends varied
significantly by state. Overall, 64% of blastomycosis-associated hospitalizations
were among men and the median age at hospitalization was 53 years. This analysis
provides a complete epidemiologic description of blastomycosis-associated
hospitalizations throughout the endemic area in the United States.
PMID- 25126840
TI - Parasite pressures on feral honey bees (Apis mellifera sp.).
AB - Feral honey bee populations have been reported to be in decline due to the spread
of Varroa destructor, an ectoparasitic mite that when left uncontrolled leads to
virus build-up and colony death. While pests and diseases are known causes of
large-scale managed honey bee colony losses, no studies to date have considered
the wider pathogen burden in feral colonies, primarily due to the difficulty in
locating and sampling colonies, which often nest in inaccessible locations such
as church spires and tree tops. In addition, little is known about the provenance
of feral colonies and whether they represent a reservoir of Varroa tolerant
material that could be used in apiculture. Samples of forager bees were collected
from paired feral and managed honey bee colonies and screened for the presence of
ten honey bee pathogens and pests using qPCR. Prevalence and quantity was similar
between the two groups for the majority of pathogens, however feral honey bees
contained a significantly higher level of deformed wing virus than managed honey
bee colonies. An assessment of the honey bee race was completed for each colony
using three measures of wing venation. There were no apparent differences in wing
morphometry between feral and managed colonies, suggesting feral colonies could
simply be escapees from the managed population. Interestingly, managed honey bee
colonies not treated for Varroa showed similar, potentially lethal levels of
deformed wing virus to that of feral colonies. The potential for such findings to
explain the large fall in the feral population and the wider context of the
importance of feral colonies as potential pathogen reservoirs is discussed.
PMID- 25126841
TI - The complete genome sequence of Escherichia coli EC958: a high quality reference
sequence for the globally disseminated multidrug resistant E. coli O25b:H4-ST131
clone.
AB - Escherichia coli ST131 is now recognised as a leading contributor to urinary
tract and bloodstream infections in both community and clinical settings. Here we
present the complete, annotated genome of E. coli EC958, which was isolated from
the urine of a patient presenting with a urinary tract infection in the Northwest
region of England and represents the most well characterised ST131 strain.
Sequencing was carried out using the Pacific Biosciences platform, which provided
sufficient depth and read-length to produce a complete genome without the need
for other technologies. The discovery of spurious contigs within the assembly
that correspond to site-specific inversions in the tail fibre regions of
prophages demonstrates the potential for this technology to reveal dynamic
evolutionary mechanisms. E. coli EC958 belongs to the major subgroup of ST131
strains that produce the CTX-M-15 extended spectrum beta-lactamase, are
fluoroquinolone resistant and encode the fimH30 type 1 fimbrial adhesin. This
subgroup includes the Indian strain NA114 and the North American strain JJ1886. A
comparison of the genomes of EC958, JJ1886 and NA114 revealed that differences in
the arrangement of genomic islands, prophages and other repetitive elements in
the NA114 genome are not biologically relevant and are due to misassembly. The
availability of a high quality uropathogenic E. coli ST131 genome provides a
reference for understanding this multidrug resistant pathogen and will facilitate
novel functional, comparative and clinical studies of the E. coli ST131 clonal
lineage.
PMID- 25126843
TI - Trochlear groove osteochondritis dissecans of the knee patellofemoral joint.
AB - BACKGROUND: The trochlear groove is the rarest location for osteochondritis
dissecans (OCD) of the knee, with only about 50 previously reported cases, most
of which were treated before the advent of magnetic resonance imaging (MRI) and
modern techniques of cartilage fixation or osteochondral transplantation. The
purpose of this multicenter study was to assess the patient presentation and
clinical, radiographic, and functional results of treatment for trochlear groove
OCD lesions. METHODS: Hospital records from 5 institutions of the Research in
Osteochondritis of the Knee (ROCK) study group were retrospectively reviewed for
cases of trochlear groove OCD. Demographics, clinical presentation, diagnosis,
treatment, time to pain resolution, and return to sports were recorded. Lesion
appearance, size, stability, and time to radiographic healing were evaluated on
plain x-rays and MRIs. RESULTS: Trochlear groove OCD lesions were evaluated in 24
knees in 21 adolescents (17 male, 4 female), with an average age of 14 years
(range, 10 to 18 y). Fifty-four percent (13/24) of the lesions were identifiable
on radiographs, and all were identifiable on MRI, 38% of which (9/24) was
unstable. One fourth (6/24) of knees had coexistent femoral condyle OCD lesions.
Treatment outcomes were evaluated in patients with a minimum of 1-year follow-up
(average: 3 y; range: 1 to 12 y) or healing before 1 year. Half of the knees
(2/4) treated nonoperatively and two thirds (8/12) treated operatively showed
radiographic signs of healing with patients returning to full activity without
pain. Operative treatment success rates were as follows: drilling (3/3), fixation
(3/3), microfracture (1/2), drilling with subsequent delayed microfracture (1/1),
and drilling with fixation (0/3). CONCLUSIONS: MRI aids in the diagnosis and
staging of trochlear groove OCD lesions, as almost one half may not be
identifiable on radiographs, and one quarter are associated with OCD lesions in
other locations of the same knee. Multiple operative treatments can be used to
achieve healing or resolution of symptoms in stable and unstable lesions;
however, a larger comparative study is needed to make specific recommendations.
LEVEL OF EVIDENCE: Therapeutic Level IV.
PMID- 25126842
TI - Promiscuous speciation with gene flow in silverside fish genus Odontesthes
(Atheriniformes, Atherinopsidae) from south western Atlantic Ocean basins.
AB - The present paper integrates phylogenetic and population genetics analyses based
on mitochondrial and nuclear molecular markers in silversides, genus Odontesthes,
from a non-sampled area in the SW Atlantic Ocean to address species
discrimination and to define Managements Units for sustainable conservation. All
phylogenetic analyses based on the COI mitochondrial gene were consistent to
support the monophyly of the genus Odontesthes and to include O. argentinensis,
O. perugiae-humensis and some O. bonariensis haplotypes in a basal polytomy
conforming a major derivative clade. Microsatellites data revealed somewhat
higher genetic variability values in the O. argentinensis-perugia populations
than in O. bonariensis and O. perugia-humensis taxa. Contrasting population
genetics structuring emerged from mitochondrial and microsatellites analyses in
these taxa. Whereas mitochondrial data supported two major groups (O.
argentinensis-perugia-humensis vs. O. bonariensis-perugiae-humensis populations),
microsatellite data detected three major genetic entities represented by O.
bonariensis, O. perugiae-humensis and an admixture of populations belonging to O.
argentinensis-perugiae respectively. Therefore, the star COI polytomy in the tree
topology involving these taxa could be interpreted by several hypothetic
scenarios such as the existence of shared ancestral polymorphisms, incomplete
lineage sorting in a radiating speciation process and/or reticulation events.
Present findings support that promiscuous and recent contact between incipient
species sharing asymmetric gene flow exchanges, blurs taxa boundaries yielding
complicated taxonomy and Management Units delimitation in silverside genus
Odontesthes from SW Atlantic Ocean basins.
PMID- 25126844
TI - Upper thoracic pedicle screws loss of fixation causing spinal cord injury.
PMID- 25126846
TI - Highly informative single-copy nuclear microsatellite DNA markers developed using
an AFLP-SSR approach in black spruce (Picea mariana) and red spruce (P. rubens).
AB - BACKGROUND: Microsatellites or simple sequence repeats (SSRs) are highly
informative molecular markers for various biological studies in plants. In spruce
(Picea) and other conifers, the development of single-copy polymorphic genomic
microsatellite markers is quite difficult, owing primarily to the large genome
size and predominance of repetitive DNA sequences throughout the genome. We have
developed highly informative single-locus genomic microsatellite markers in black
spruce (Picea mariana) and red spruce (Picea rubens) using a simple but efficient
method based on a combination of AFLP and microsatellite technologies. PRINCIPAL
FINDINGS: A microsatellite-enriched library was constructed from genomic AFLP DNA
fragments of black spruce. Sequencing of the 108 putative SSR-containing clones
provided 94 unique sequences with microsatellites. Twenty-two of the designed 34
primer pairs yielded scorable amplicons, with single-locus patterns. Fourteen of
these microsatellite markers were characterized in 30 black spruce and 30 red
spruce individuals drawn from many populations. The number of alleles at a
polymorphic locus ranged from 2 to 18, with a mean of 9.3 in black spruce, and
from 3 to 15, with a mean of 6.2 alleles in red spruce. The polymorphic
information content or expected heterozygosity ranged from 0.340 to 0.909 (mean =
0.67) in black spruce and from 0.161 to 0.851 (mean = 0.62) in red spruce. Ten
SSR markers showing inter-parental polymorphism inherited in a single-locus
Mendelian mode, with two cases of distorted segregation. Primer pairs for almost
all polymorphic SSR loci resolved microsatellites of comparable size in Picea
glauca, P. engelmannii, P. sitchensis, and P. abies. SIGNIFICANCE: The AFLP-based
microsatellite-enriched library appears to be a rapid, cost-effective approach
for isolating and developing single-locus informative genomic microsatellite
markers in black spruce. The markers developed should be useful in black spruce,
red spruce and other Picea species for various genetics, genomics, breeding,
forensics, conservation studies and applications.
PMID- 25126848
TI - A viable population of the European red squirrel in an urban park.
AB - Whether urban parks can maintain viable and self-sustaining populations over the
long term is questionable. In highly urbanized landscapes, urban parks could play
a role in biodiversity conservation by providing habitat and resources to native
species. However, populations inhabiting urban parks are usually small and
isolated, leading to increased demographic stochasticity and genetic drift, with
expected negative consequences on their viability. Here, we investigated a
European red squirrel population located in an urban park close to Paris, France
(Parc de Sceaux; 184 ha) to assess its viability. Using mitochondrial D-loop
sequences and 13 microsatellite loci, we showed that the population presented
high levels of genetic variation and no evidence of inbreeding. The size of the
population was estimated at 100-120 individuals based on the comparison of two
census techniques, Distance Sampling and Capture-Mark-Recapture. The estimated
heterozygosity level and population size were integrated in a Population
Viability Analysis to project the likelihood of the population's persistence over
time. Results indicate that the red squirrel population of this urban park can be
viable on the long term (i.e. 20 years) for a range of realistic demographic
parameters (juvenile survival at least >40%) and immigration rates (at least one
immigration event every two years). This study highlights that urban parks can be
potential suitable refuges for the red squirrel, a locally threatened species
across western European countries, provided that ecological corridors are
maintained.
PMID- 25126847
TI - A quest for miRNA bio-marker: a track back approach from gingivo buccal cancer to
two different types of precancers.
AB - Deregulation of miRNA expression may contribute to tumorigenesis and other patho
physiology associated with cancer. Using TLDA, expression of 762 miRNAs was
checked in 18 pairs of gingivo buccal cancer-adjacent control tissues. Expression
of significantly deregulated miRNAs was further validated in cancer and examined
in two types of precancer (leukoplakia and lichen planus) tissues by primer
specific TaqMan assays. Biological implications of these miRNAs were assessed
bioinformatically. Expression of hsa-miR-1293, hsa-miR-31, hsa-miR-31* and hsa
miR-7 were significantly up-regulated and those of hsa-miR-206, hsa-miR-204 and
hsa-miR-133a were significantly down-regulated in all cancer samples. Expression
of only hsa-miR-31 was significantly up-regulated in leukoplakia but none in
lichen planus samples. Analysis of expression heterogeneity divided 18 cancer
samples into clusters of 13 and 5 samples and revealed that expression of 30
miRNAs (including the above-mentioned 7 miRNAs), was significantly deregulated in
the cluster of 13 samples. From database mining and pathway analysis it was
observed that these miRNAs can significantly target many of the genes present in
different cancer related pathways such as "proteoglycans in cancer", PI3K-AKT
etc. which play important roles in expression of different molecular features of
cancer. Expression of hsa-miR-31 was significantly up-regulated in both cancer
and leukoplakia tissues and, thus, may be one of the molecular markers of
leukoplakia which may progress to gingivo-buccal cancer.
PMID- 25126849
TI - Financial costs of large carnivore translocations--accounting for conservation.
AB - Human-carnivore conflict continues to present a major conservation challenge
around the world. Translocation of large carnivores is widely implemented but
remains strongly debated, in part because of a lack of cost transparency. We
report detailed translocation costs for three large carnivore species in Namibia
and across different translocation scenarios. We consider the effect of various
parameters and factors on costs and translocation success. Total translocation
cost for 30 individuals in 22 events was $80,681 (US Dollars). Median
translocation cost per individual was $2,393, and $2,669 per event. Median cost
per cheetah was $2,760 (n = 23), and $2,108 per leopard (n = 6). One hyaena was
translocated at a cost of $1,672. Tracking technology was the single biggest cost
element (56%), followed by captive holding and feeding. Soft releases, prolonged
captivity and orphaned individuals also increased case-specific costs. A
substantial proportion (65.4%) of the total translocation cost was successfully
recovered from public interest groups. Less than half the translocations were
confirmed successes (44.4%, 3 unknown) with a strong species bias. Four leopards
(66.7%) were successfully translocated but only eight of the 20 cheetahs (40.0%)
with known outcome met these strict criteria. None of the five habituated
cheetahs was translocated successfully, nor was the hyaena. We introduce the
concept of Individual Conservation Cost (ICC) and define it as the cost of one
successfully translocated individual adjusted by costs of unsuccessful events of
the same species. The median ICC for cheetah was $6,898 and $3,140 for leopard.
Translocations are costly, but we demonstrate that they are not inherently more
expensive than other strategies currently employed in non-lethal carnivore
conflict management. We conclude that translocation should be one available
option for conserving large carnivores, but needs to be critically evaluated on a
case-by-case basis.
PMID- 25126852
TI - Mapping and introgression of QTL involved in fruit shape transgressive
segregation into 'piel de sapo' melon (cucumis melo l.) [corrected].
AB - A mapping F2 population from the cross 'Piel de Sapo' * PI124112 was selectively
genotyped to study the genetic control of morphological fruit traits by QTL
(Quantitative Trait Loci) analysis. Ten QTL were identified, five for FL (Fruit
Length), two for FD (Fruit Diameter) and three for FS (Fruit Shape). At least one
robust QTL per character was found, flqs8.1 (LOD = 16.85, R2 = 34%), fdqs12.1
(LOD = 3.47, R2 = 11%) and fsqs8.1 (LOD = 14.85, R2 = 41%). flqs2.1 and fsqs2.1
cosegregate with gene a (andromonoecious), responsible for flower sex
determination and with pleiotropic effects on FS. They display a positive
additive effect (a) value, so the PI124112 allele causes an increase in FL and
FS, producing more elongated fruits. Conversely, the negative a value for flqs8.1
and fsqs8.1 indicates a decrease in FL and FS, what results in rounder fruits,
even if PI124112 produces very elongated melons. This is explained by a
significant epistatic interaction between fsqs2.1 and fsqs8.1, where the effects
of the alleles at locus a are attenuated by the additive PI124112 allele at
fsqs8.1. Roundest fruits are produced by homozygous for PI124112 at fsqs8.1 that
do not carry any dominant A allele at locus a (PiPiaa). A significant interaction
between fsqs8.1 and fsqs12.1 was also detected, with the alleles at fsqs12.1
producing more elongated fruits. fsqs8.1 seems to be allelic to QTL discovered in
other populations where the exotic alleles produce elongated fruits. This model
has been validated in assays with backcross lines along 3 years and ultimately
obtaining a fsqs8.1-NIL (Near Isogenic Line) in 'Piel de Sapo' background which
yields round melons.
PMID- 25126851
TI - Large-scale, high-resolution multielectrode-array recording depicts functional
network differences of cortical and hippocampal cultures.
AB - Understanding the detailed circuitry of functioning neuronal networks is one of
the major goals of neuroscience. Recent improvements in neuronal recording
techniques have made it possible to record the spiking activity from hundreds of
neurons simultaneously with sub-millisecond temporal resolution. Here we used a
512-channel multielectrode array system to record the activity from hundreds of
neurons in organotypic cultures of cortico-hippocampal brain slices from mice. To
probe the network structure, we employed a wavelet transform of the cross
correlogram to categorize the functional connectivity in different frequency
ranges. With this method we directly compare, for the first time, in any
preparation, the neuronal network structures of cortex and hippocampus, on the
scale of hundreds of neurons, with sub-millisecond time resolution. Among the
three frequency ranges that we investigated, the lower two frequency ranges
(gamma (30-80 Hz) and beta (12-30 Hz) range) showed similar network structure
between cortex and hippocampus, but there were many significant differences
between these structures in the high frequency range (100-1000 Hz). The high
frequency networks in cortex showed short tailed degree-distributions, shorter
decay length of connectivity density, smaller clustering coefficients, and
positive assortativity. Our results suggest that our method can characterize
frequency dependent differences of network architecture from different brain
regions. Crucially, because these differences between brain regions require
millisecond temporal scales to be observed and characterized, these results
underscore the importance of high temporal resolution recordings for the
understanding of functional networks in neuronal systems.
PMID- 25126853
TI - Erasing the past: a new identity for the Damoclean pathogen causing South
American leaf blight of rubber.
AB - BACKGROUND: South American leaf blight (SALB) of rubber has been the main
constraint to production in its neotropical centre of origin since commercial
plantations were first established. The fungal causal agent was identified and
described more than a century ago but its precise placement within the Ascomycota
still remains uncertain. Indeed, such is the ambiguity surrounding the pathogen
that each of the spore morphs would, according to their present classification,
be placed in different ascomycete families: the Microcyclus sexual morph in the
Planistromellaceae and the two purported asexual morphs--Fusicladium and
Aposphaeria--in the Venturiaceae and Lophiostomataceae, respectively. Given the
historical importance of the fungus and the ever-menacing threat that it poses to
rubber production in the Palaeotropics--and, thus to the rubber industry and to
the global economy--its phylogeny, as well as its biology, should be resolved as
a matter of urgency. METHODS AND RESULTS: Here, six genomic regions (LSU rRNA,
mtSSU, MCM7, EF-1alpha, Act and ITS) were used for reconstructing the molecular
phylogeny of the SALB fungus based on material collected throughout Brazil. The
analyses support the classification of the fungus in the family
Mycosphaerellaceae s. str. (Capnodiales, Dothideomycetes) and place it firmly
within the clade Pseudocercospora s. str., now accepted as one of the distinct
genera within Mycosphaerellaceae. The new combination Pseudocercospora ulei is
proposed and the life cycle of the fungus is confirmed, based on both
experimental and phylogenetic evidence, with the Aposphaeria morph shown to have
a spermatial rather than an infective-dispersal function. CONCLUSIONS: Because
the phylogeny of the SALB fungus has now been clarified, new insights of its
epidemiology and genomics can be gained following comparison with closely
related, better-researched crop pathogens.
PMID- 25126854
TI - Safety and immunogenicity of a 13-valent pneumococcal conjugate vaccine
manufactured with and without polysorbate 80 given to healthy infants at 2, 3, 4
and 12 months of age.
AB - BACKGROUND: Polysorbate 80 (P80), a nonionic detergent used to solubilize
proteins, is used in both oral and injectable medications including vaccines.
Development studies with 13-valent pneumococcal conjugate vaccine (PCV13) showed
that adding P80 resulted in a more robust manufacturing process. Before adding
P80 to the formulation of PCV13, we investigated the immunogenicity and safety of
PCV13 with and without P80. METHODS: Phase 3, parallel-group, randomized, active
controlled, double-blind multicenter trial was conducted at 15 sites in Poland.
Healthy infants were randomized (1:1) to receive PCV13+P80 or PCV13 without P80
given at ages 2, 3, 4 and 12 months concomitantly with DTaP-IPV-Hib at 2, 3 and 4
months; hepatitis B at 2 months and measles, mumps, and rubella at 12 months.
Serotype-specific antipneumococcal immune responses were evaluated using
antipolysaccharide capsular immunoglobulin (Ig)G responses and opsonophagocytic
activity (OPA) assay. Safety data were also collected. RESULTS: The 2 treatment
groups were demographically similar. Following the infant immunization series,
anticapsular IgG antibody geometric mean concentrations and OPA geometric mean
titers for each serotype were within 2-fold between the 2 groups. Formal
noninferiority criteria for comparison of proportion of responders (subjects with
IgG titers >=0.35 MUg/mL) were met for 11 of the 13 serotypes. Overall population
responses were highly similar. Anticapsular IgG responses were also within 2-fold
following the toddler dose. Safety profiles were similar between the 2 groups.
CONCLUSIONS: Addition of P80 to PCV13 did not adversely affect PCV13
immunogenicity or safety when compared with vaccine formulated without P80.
PMID- 25126855
TI - Human parechovirus infection in neonatal intensive care.
AB - BACKGROUND: Approximately 5-6% of all infective episodes in neonatal intensive
care unit (NICU) are of viral origin. Previous studies suggest that human
parechovirus (HPeV) infection presents most commonly in term infants, as a sepsis
like syndrome in which meningoencephalitis is prominent. Our aim was to study the
infection rate and associated features of HPeV. METHODS: Blood samples were taken
from NICU babies older than 48 hours, who were being investigated for late onset
sepsis. Clinical and laboratory data were collected at the time of the suspected
sepsis episode. Samples were tested using universal primers and probe directed at
the 5'-untranslated region of the HPeV genome by reverse transcriptase polymerase
chain reaction (RT-PCR). Results were confirmed by electrophoresis and DNA
sequencing. RESULTS: HPeV was detected in 11 of 84 samples (13%). These infants
had a mean [interquartile range (IQR)] gestational age of 28.9 (26.9-30.6) weeks
and mean birth weight of 1.26 (SD = 0.72) kg. The median day of presentation was
16 (IQR: 11-27). These characteristics were similar to the infants without
positive viral detection. Six infants presented with respiratory signs. One
infant presented with signs of meningitis. Six of the 11 episodes of HPeV
infection occurred during the winter months (December to February). No HPeV
positive infants had abnormal findings on their 28-day cranial ultrasound
examination. CONCLUSIONS: We found an HPeV infection rate of 13% in infants being
tested for late onset sepsis. HPeV should be considered as a possible cause of
sepsis-like symptoms in preterm infants.
PMID- 25126856
TI - Clinical profile and predictors of fatal Rocky Mountain spotted fever in children
from Sonora, Mexico.
AB - BACKGROUND: Rocky Mountain spotted fever (RMSF) is an increasingly important
cause of preventable mortality in children in Sonora, Mexico. Although early
treatment with tetracycline has shown to prevent fatal outcome, the disease
remains a life-threatening condition, particularly for children. This study
describes the clinical factors associated with pediatric mortality due to RMSF in
Sonora, in order to guide healthcare practices. METHODS: This is a retrospective
analysis of 104 children consecutively hospitalized at the major pediatric
hospital of Sonora, diagnosed with RMSF between January 2004 and December 2013.
Descriptive statistics and multiple logistic regression were used to identify
risk factors for fatal outcome. RESULTS: The case fatality ratio in this cohort
was 20.2%. Children were hospitalized after a median of 6 days from onset of
symptoms including fever (100%), rash involving palms and soles (88.5%) and
headache (79.8%); 90.4% of fatal cases had low platelet counts (<50,000/MUL) and
33.3% showed serum creatinine concentrations above the normal value. Acute kidney
injury increased mortality, odds ratio (OR(adj)) = 4.84, 95% confidence interval
(CI): 1.2-16.2, as well as delay in treatment (>= 5th day from onset) with
doxycycline, OR(adj) = 2.62, 95% CI: 1.24-5.52 and hemorrhage, OR(adj) = 6.11,
95% CI: 1.89-19.69. CONCLUSIONS: RMSF is a public health problem in Sonora.
Clinically, fatal cases differ from non-fatal cases in renal function and
hemorrhagic manifestations, although these findings may occur too late for a
timely intervention. First-line providers must be educated to harbor a timely
suspicion of RMSF, and should provide empiric treatment with doxycycline when
febrile patients first present for care.
PMID- 25126857
TI - Fatal human bocavirus infection in an 18-month-old child with chronic lung
disease of prematurity.
AB - A fatal case of human bocavirus 1 pulmonary infection in an 18-month-old
prematurely born child is described. Despite conventional and oscillatory
ventilatory support, intractable hyperinflation developed with bilateral
pneumothorax and acute cardiac failure 3 days after the onset of respiratory
symptoms.
PMID- 25126858
TI - Implicit learning in individuals with autism spectrum disorders: a meta-analysis.
AB - BACKGROUND: Individuals with autism spectrum disorders (ASDs) are characterized
by social communication difficulties and behavioural rigidity. Difficulties in
learning from others are one of the most devastating features of this group of
conditions. Nevertheless, the nature of learning difficulties in ASDs is still
unclear. Given the relevance of implicit learning for social and communicative
functioning, a link has been hypothesized between ASDs and implicit learning
deficit. However, studies that have employed formal testing of implicit learning
in ASDs provided mixed results. METHOD: We undertook a systematic search of
studies that examined implicit learning in ASDs using serial reaction time (SRT),
alternating serial reaction time (ASRT), pursuit rotor (PR), and contextual
cueing (CC) tasks, and synthesized the data using meta-analysis. A total of 11
studies were identified, representing data from 407 individuals with ASDs and
typically developing comparison participants. RESULTS: The results indicate that
individuals with ASDs do not differ in any task considered [SRT and ASRT task:
standardized mean difference (SMD) -0.18, 95% confidence interval (CI) -0.71 to
0.36; PR task: SMD -0.34, 95% CI -1.04 to 0.36; CC task: SMD 0.27, 95% CI -0.07
to 0.60]. CONCLUSIONS: Based on our synthesis of the existing literature, we
conclude that individuals with ASDs can learn implicitly, supporting the
hypothesis that implicit learning deficits do not represent a core feature in
ASDs.
PMID- 25126859
TI - Solution processed n-In2O3 nanostructures for organic-inorganic hybrid p-n
junctions.
AB - Solution processed organic-inorganic bulk hybrid heterostructures are nowadays
considered as the most promising elements to perform efficient optoelectronic
functions. In this regard, In2O3 based hybrid heterostructures were fabricated
using polypyrrole and their role as efficient interfacial layers was studied
using polypyrrole/ZnO nanowires. The In2O3 nanostructures were synthesized
through a facile wet chemical approach at an average scale of less than 10 nm in
cubic phase. The presence of O and In related defects was studied through
emission spectra; these were also found to exhibit their predominance in Raman
measurements. The n-type characteristics and donor density value of around 10(20)
cm(-3) were evaluated for the In2O3 specimens via Mott-Schottky plots. The role
of In2O3 nanostructures as active/interfacial layers was then studied using the
current-voltage characteristics obtained across the hybrid heterostructures made
of polypyrrole/In2O3, polypyrrole/ZnO and polypyrrole/In2O3/ZnO. Organic
inorganic p-n diodes were obtained via in situ chemical polymerization, drop
casting and hydrothermal routes. Cyclic voltammograms and Nyquist plots were used
to study the reduction mechanism taking place in the nanostructures that actually
results with the formation of metallic In, which plays a vital role in
establishing the required conduction electrons. The same has been reasoned for
the improved rectification characteristics observed across the diodes.
PMID- 25126860
TI - Regulation of insulin sensitivity by adiponectin and its receptors in response to
physical exercise.
AB - Adiponectin is an adipocyte-derived abundant plasma protein, also called Acrp30
(adipocyte complement-related protein), adipoQ, ApM1 (AdiPose Most abundant Gene
transcript 1), or GBP28 (gelatin-binding protein-28). Insulin resistance is a
primary contributing factor in the pathogenesis of type 2 diabetes. Adiponectin
binds to adiponectin receptors AdipoR1 and AdipoR2, and exerts antidiabetic
effects via activation of AMPK and PPAR-alpha pathways, respectively. In the same
sense chronic exercise has been showed to induce numerous metabolic factors that
can improve insulin resistance. It has been reported that physical exercise
training increases adiponectin receptors, which may mediate the improvement of
insulin resistance in response to exercise, which is the focus of the present
review.
PMID- 25126861
TI - Expression analysis of GADD45gamma, MEG3, and p8 in pituitary adenomas.
AB - Preceding studies have indicated that aberrant expression levels rather than
genetic changes of GADD45gamma, MEG3, and p8 gene might play a role in the
pathogenesis of pituitary adenomas. We analysed their expression in various
normal human tissues and in different pituitary tumour types, and investigated
GADD45gamma mutations in a subset of adenomas. Absolute quantification by real
time RT-PCR was performed in 24 normal tissues as well as in 34 nonfunctioning,
24 somatotroph, 12 corticotroph adenomas, 4 prolactinomas, 1 FSHoma, and in 6
normal pituitaries. Furthermore, we investigated the relationship between
clinical data and gene expression. A subset was screened for GADD45gamma
mutations by single strand conformation polymorphism analysis (SSCP) and
sequencing. All normal human tissues expressed GADD45gamma, MEG3, and p8 mRNA.
For GADD45gamma, significantly lower expression levels were found in
nonfunctioning adenomas compared with normal pituitary and somatotroph adenomas.
P8 and MEG3 mRNA levels were significantly lower in nonfunctioning and
corticotroph adenomas compared with normal pituitary. Expression of GADD45gamma
was significantly higher in pituitary adenomas of female patients. No mutation
was found in the GADD45gamma gene. GADD45gamma, MEG3, and p8 appear to have
physiological functions in a variety of human tissues. GADD45gamma, MEG3, and P8
may be involved in the pathogenesis of nonfunctioning and corticotroph pituitary
tumours. Female gender seems to predispose to slightly higher GADD45gamma
expression in pituitary adenomas. Mutations of the GADD45gamma are unlikely to be
involved in the pathogenesis of pituitary adenomas.
PMID- 25126863
TI - Awareness, perception and coverage of tetanus immunisation in women of child
bearing age in an urban district of Lagos, Nigeria.
AB - AIMS AND OBJECTIVES: This study assessed the level of awareness and perception of
women of child bearing age to tetanus immunisation and determines the cover- age
rate in Ojodu Local Council Development Area (LCDA) of Lagos State, Nigeria.
SUBJECTS AND METHODS: This is a descriptive cross-sectional study of 288 women of
child bearing age selected using multistage sampling technique. Information was
obtained using structured close-ended questionnaire. Data analysis was done using
Epi-InfoTM software, version 3.5.1. RESULTS: There was high level of awareness of
tetanus immunisation among respondents (89%) and as a method of prevention of
tetanus (76%). There was a positive association between the level of awareness
and respondents' educational level and occupation (p < 0.05). However, there is a
low level of awareness regarding the number of doses of the vaccine required in
pregnancy(14.4%) and for life protection (19.5%). Those who ever received the
vaccine,got it post-injury (48.9%) and in pregnancy (45.2%). Age, occupation and
parity were positively associated with receiving the vaccine (p < 0.05), while
parity and marital status were positively associated with number of dose of
vaccine received (p < 0.05). Only about 20% of the respondents had received two
or more doses of the vaccine. CONCLUSION: This study concludes that despite the
high level of awareness about tetanus and tetanus immunisation, there is a low
coverage rate of tetanus immunisation among women of child bearing age in Ojodu
LCDA of Lagos State. Women of child bearing age should also be targeted at the
community level in tetanus immunisation campaign programme.
PMID- 25126864
TI - A cross-sectional study for algorithm in diagnosing simple uncomplicated malaria
in children in health facilities without laboratory backup in Nigeria.
AB - AIMS AND OBJECTIVES: The objective of this study was to determine an algorithm
for malaria diagnosis using presenting signs and symptoms of children (aged 0-13
years) with uncomplicated malaria in Gwagwalada Area Council of Abuja, Nigeria.
MATERIALS AND METHODS: A validated questionnaire was used to obtain relevant data
from 400 children diagnosed presumptively of simple malaria by clinicians and 400
other children of similar sex and age considered as not having malaria. Giemsa
stained thick blood films were used to determine parasitaemia. Data obtained was
analysed using Epi-Info version 3.3.2. RESULTS: Thirty-eight per cent of children
with presumptive diagnosis of malaria had parasitaemia. Fever, rigor, vomiting,
jaundice, pallor and spleen enlargement had significant statistical relationship
with parasitaemia on bivariate analysis, but only fever (p=0.00), rigor (p=0.00),
vomiting (p=0.00), and pallor (p=0.00) maintained the relationship when subjected
to logistic regression analysis. But these symptoms individually had low
sensitivity and/or specificity. Candidate algorithms (combinations of symptoms)
were then successively subjected to bivariate, logistic and validity analyses.
Fever with vomiting gave the highest sensitivity (56.2%), specificity (76.4%) and
PPV (60.0%) and were therefore adopted as the algorithm of choice. CONCLUSION AND
RECOMMENDATIONS: Children presenting with fever and vomiting without any other
obvious cause in health facilities without laboratory support in the research
area should receive antimalarial treatment, to help reduce the malaria scourge.
This algorithm should be field-tested and if found reliable should be adopted to
ease the problem of malaria diagnosis in peripheral health facilities.
PMID- 25126862
TI - Delivery of full-length factor VIII using a piggyBac transposon vector to correct
a mouse model of hemophilia A.
AB - Viral vectors have been used for hemophilia A gene therapy. However, due to its
large size, full-length Factor VIII (FVIII) cDNA has not been successfully
delivered using conventional viral vectors. Moreover, viral vectors may pose
safety risks, e.g., adverse immunological reactions or virus-mediated
cytotoxicity. Here, we took advantages of the non-viral vector gene delivery
system based on piggyBac DNA transposon to transfer the full-length FVIII cDNA,
for the purpose of treating hemophilia A. We tested the efficiency of this new
vector system in human 293T cells and iPS cells, and confirmed the expression of
the full-length FVIII in culture media using activity-sensitive coagulation
assays. Hydrodynamic injection of the piggyBac vectors into hemophilia A mice
temporally treated with an immunosuppressant resulted in stable production of
circulating FVIII for over 300 days without development of anti-FVIII antibodies.
Furthermore, tail-clip assay revealed significant improvement of blood
coagulation time in the treated mice. piggyBac transposon vectors can facilitate
the long-term expression of therapeutic transgenes in vitro and in vivo. This
novel gene transfer strategy should provide safe and efficient delivery of FVIII.
PMID- 25126865
TI - The effect of a sexuality education programme among out- of- school adolescents
in Lagos, Nigeria.
AB - AIMS AND OBJECTIVES: This study was conducted to assess the effect of a community
based sexuality education programme on the sexual health knowledge and practices
of out of school female adolescents. SUBJECTS AND METHODS: This Intervention
study was conducted in two markets within Lagos, Nigeria. Representative samples
of adolescents were interviewed on their sexual health knowledge and practices.
An Education- entertainment programme provided sexuality education to adolescents
in Mushin market only (intervention group) followed by post intervention surveys
in Mushin market and Sangrouse market (control group). The pre and post
intervention surveys were compared 6 months post intervention to detect any
changes. RESULTS: Sexual health knowledge and behaviour was similar among
respondents in both markets pre intervention. Post intervention, the sexual
health knowledge of the respondents in the intervention site improved
significantly. (p<0.05) Fewer adolescents initiated sex in the intervention site
than in the control site and contraceptive use increased. However among the
sexually active, there was no significant change in their condom use and number
of sexual partners. CONCLUSION: Community based health education programmes can
be used to provide effective sexuality education for out of school adolescents.
Provision should be made by government and non-governmental organisations during
adolescent reproductive health programming for sexuality education targeted at
out of school adolescents.
PMID- 25126866
TI - The effect of a short anti-smoking awareness programme on the knowledge, attitude
and practice of cigarette smoking among secondary school students in Lagos state,
Nigeria.
AB - This study aimed to assess the effect of a short school-based anti-smoking
program on the knowledge, attitude and practice of cigarette smoking among
students in secondary schools in Lagos State. SUBJECTS AND METHODS: A non
randomized, controlled intervention study was done among respondents selected
using multi-stage sampling. Baseline data was collected using self-administered
questionnaires. An anti-smoking awareness programme was carried out among
students in the intervention group using health talks, information leaflets and
posters. Post-intervention data collection took place three months later.
RESULTS: There were significant increments in the mean knowledge and attitude
scores after the intervention. There was however no statistically significant
change in the current smoking habits of respondents (4% vs. 3%; p=0.41)in the
intervention group. Nevertheless, in the intervention group, the number of never-
smokers who reported that they were likely to initiate cigarette smoking within
the next year significantly reduced. There was also a significant increase in the
proportion of current smokers who desired to quit smoking. CONCLUSION: Even brief
anti-smoking programs of this nature are effective at improving the knowledge and
modifying the attitude of the respondents but do not improve smoking habits. It
however motivated the desire to quit among current smokers. Health education
sessions and periodic anti-smoking programmes should be introduced into the
secondary school curriculum. More intensive approaches may be needed to influence
the smoking behaviour of adolescent smokers.
PMID- 25126867
TI - Effects of interval exercise training programme on the indices of adiposity and
biomarker of inflammation in hypertension: a randomised controlled trial.
AB - AIMS AND OBJECTIVES: Hypertension remains a significant risk factor in
cardiovascular morbidity and mortality. The purpose of the present study was to
investigate the effects of 8 weeks interval training programme on blood pressure,
aerobic capacity (VO max), indices of adiposity and marker of inflammation in
black African men with essential hypertension. PATIENTS AND METHODS: Two hundred
and forty five (245) male subjects with stage 1 and 2 (systolic blood pressure
[SBP] between 140-179 & diastolic blood pressure [DBP] between 90-109 mmHg)
essential hypertension were age matched and grouped into experimental and control
groups. The experimental (n=140; 58.90 +/- 7.35 years) group involved in an 8
weeks interval training (60-79% HRmax) programme of between 45 and 60 minutes,
while age-matched control hypertensive (n=105; 58.27+/-6.24 years) group remain
sedentary during this period. All subjects in both groups were on
antihypertensive drugs throughout the study period. Cardiovascular parameters
(SBP, DBP) & VO max and percent body fat [%BF], waist to hip ratio [WHR] and C
reactive protein [CRP] were assessed. Independent t-test and Pearson correlation
test were used in data analysis. RESULTS: Findings of the study revealed
significant decreased effects of interval training programme on SBP, DBP, %BF,
WHR and CRP and significant increased effect on VO max at p< 0.05. Also, changes
in CRP as a result of exercise training significantly and positively correlated
with changes in SBP, DBP, %BF, WHR, CRP and negatively correlated with VO max at
p< 0.05.
PMID- 25126868
TI - The knowledge and attitude of non-ophthalmic medical doctors towards glaucoma in
two tertiary institutions in south eastern Nigeria.
AB - AIMS AND OBJECTIVES: This study is aimed at determining how much knowledge of
glaucoma the non-ophthalmic medical doctors still possess and their personal
attitudes toward glaucoma. PATIENTS AND METHODS: Self- administered
questionnaires were randomly distributed to the non-ophthalmic medical doctors in
two specialist hospitals in south eastern Nigeria: The data obtained were the
age, sex, professional and number of years of practice of the participants, their
knowledge of the symptoms/ aetiology/risk factors, examination/investigation,
treatment of glaucoma as well as their personal attitude towards glaucoma.
RESULTS: There were two hundred respondents; one hundred and forty two males and
fifty eight females (M:F=2.4:1); comprising 82.5% Resident doctors; 51% of whom
had been in practice for less than 5 years.All the doctors had heard of glaucoma;
approximately seventy two per cent (72.5%) had a good knowledge of glaucoma
symptoms and 52.0% of these had been in practice for only 5 years or less.
Similarly, of the 83% of the doctors who correctly answered the questions on the
aetiology of glaucoma, majority (84.3%) had been in practice for 5 years or less.
Only 24.5% and 38.5% respectively of the doctors had a good knowledge of the
basic examination and treatment required for the management of glaucoma.There was
no statistically significant relationship between most variables tested. Only the
relationship between the knowledge of the symptoms of glaucoma and the duration
of practice of the doctors was statistically significant (p< 0.005). CONCLUSION:
Most of the non-ophthalmic medical doctors have a basic knowledge of glaucoma and
how to investigate it but showed a poor knowledge of examination and treatment
modalities. They also acknowledged the importance of regular eye checks but only
very few had had their eyes examined.
PMID- 25126869
TI - Malondialdehyde and antioxidant enzymes in second and third trimesters of pre
eclamptic Nigerian women.
AB - AIM AND OBJECTIVE: To determine changes in malondialdehyde (product of lipid
peroxidation) and antioxidant enzymes (Superoxide Dismutase, Glutathione Per
oxidase) levels in pre-eclamptic Nigerian women PATIENTS AND METHODS: A Total of
100 subjects each for pre-eclamptic,apparently normal and non pregnant women were
recruited into the study.Venous blood samples were taken from the participants
during second and third trimesters of pregnancy and at the point of contact for
non pregnant women. Malondialdehyde, glutathione peroxidase and superoxide
dismutase were measured accordingly from plasma and haemolysate prepared from
whole blood.Variables were analysed using SPSS version 16, taking level of
significance to be 0.05 RESULTS: Plasma malondialdehyde in the third trimester
(3.13+/-0.61umol/l) of pre-eclamptic subjects was higher than in the second
trimester (3.00+/-1.21umol/l).Plasma malondialdehyde in the third trimester of
normal pregnancy (2.03+/-0.71umol/l) was also found to be significantly higher
than in the second trimester (1.65+/-0.62umol/ l)(p<0.0001). Glutathione
peroxidase in pre-eclamptic subjects was significantly higher in the third
trimester (2804.11+/-1573.00U/L) as compared to the second trimester (2655.00+/
1751.30U/L), p= 0.0001.Glutathione peroxidase activity in the third trimester of
normal pregnancy(3339.50+/-1733.80U/L) was also found to be higher than in the
second trimester(3023.50+/-1115.90U/L)(p=0.131). Superoxide dismutase activity
was significantly lower in the third trimester of pre-eclamptic pregnancy when
compared to second trimester (110.40+/-59.47 Vs 118.01+/-64.41 U/ ml)(p<0.039)
.Similarly,superoxide dismutase activity was significantly lower in the third
trimester of normal pregnancy (110.40+/-59.47U/ml) than in the second
trimester(153.01+/-71.85U/ml)(p<0.0001). CONCLUSION: There was an increased level
of lipid peroxidation products,malondialdehyde in subjects with pre-eclampsia.
This was more in the third trimester. There was an increased oxidative stress in
pre-eclampsia as evidenced also by low serum level of superoxide dismutase in the
third trimester.Diet rich in antioxidant enzyme might be beneficial.
PMID- 25126870
TI - Sleep disorders in women attending antenatal care at a tertiary hospital in
Nigeria.
AB - AIMS AND OBJECTIVES: To determine the prevalence of sleep disorders in a
population of Nigerian women during pregnancy and to evaluate the frequency of
these sleep disorders according to the three trimesters of pregnancy. SUBJECTS
AND METHODS: A prospective cross-sectional design. Participants' were interviewed
at the antenatal clinic with a questionnaire to evaluate their sleep during and
before pregnancy and to appraise disturbance in their sleep according to the
trimester. RESULTS: Two hundred and three pregnant women participated in the
survey and were evaluated at one of three points in pregnancy: 1st trimester
(n=57), 2nd trimester (n=71) and 3rd trimester (n=75). Overall, the prevalence of
sleep disorder in the population surveyed was 35.5% (72/203), more women
experienced sleep disturbances in the first (42.1%) and third (40%) trimester of
pregnancy compared to the second (25.3%). In terms of types of sleep disorders;
96(47.3%) reported insomnia, 32(15.8%) sleep breathing disorders, 86(42.4%)
excessive daytime sleepiness, 172(84.7%) mild sleepiness and 64(31.5%)
significant specific awakenings. The most common reason for specific awakening
was frequent urination (78.6%). These sleep disorders were more common in the
third trimester of pregnancy but only insomnia and specific awakenings showed
statistical significance, p=0.007 and 0.031 respectively. Logistic regression
model showed that nulliparity, increased BMI and previous adverse obstetric
events had significant independent associations with sleep disorders. CONCLUSION:
Sleep disorders are common in pregnancy, notably in the first and third
trimesters.
PMID- 25126871
TI - Asthma control and quality of life in school- age children in Enugu south east,
Nigeria.
AB - AIMS AND OBJECTIVES: This study set out to assess the quality-of-life of school
age children in relation to their level of asthma control. PATIENTS AND METHODS:
A cross-sectional descriptive study of children with asthma using the Paediatric
Asthma Quality of Life questionnaire (PAQLQ) and the Asthma Therapy Assessment
Questionnaire (ATAQ) to respectively assess the health-related quality of life
and the level of asthma control. RESULTS: Ninety children with mean age of
11.8(SD, 2.8; 95% CI, 11.2 to 12.4) years, were enrolled. Fifteen children
(16.7%) were well-controlled, 17 (18.9%) were partly-controlled while 58 (64.4%)
had uncontrolled asthma. The mean asthma control score for all participants was
3.2 (95% CI, 2.8 to 3.7). The mean quality-of-life score was 5.3 (SD, 1.2; 95%
CI, 4.9 to 5.5). The lowest score was in the symptom domain: 5.1 (SD, 1.4; 95%
CI, 4.9 to 5.5), and among the 14-17 year age group (4.5 SD, 1.5; MD=1.1;
p=0.002). The emotional domain was the least affected 5.4 (SD, 1.3; 95% CI, 5.1
to 5.7). Children with well-controlled asthma had the best quality-of-life scores
in symptom domains: 5.6 (SD, 1.3; 95% CI, MD=0.6, p=0.63). Quality of life scores
were not significant in determining asthma control (MD=0.1, p=0.98). Age was
noted as the strongest quality-of-life predictor (B=-0.2, p=0.002). CONCLUSIONS:
QOL scores are better in children with well-controlled asthma. Adolescent age
group marks a period of both poor asthma control and quality of life in children
with asthma.
PMID- 25126872
TI - Ultrasonographic spleen size and haematological parameters in children with
sickle cell anaemia in Kano, Nigeria.
AB - AIMS AND OBJECTIVES: To determine spleen size using abdominal ultrasonography and
haematological parameters in steady state children with sickle cell anaemia
(SCA). SUBJECTS AND METHODS: An analytical case control study of 150 children
with SCA in steady state aged 6 months to 15 years was undertaken. Children with
HbAA matched for sex and age were used as controls. The spleen sizes of children
with SCA and the controls were determined using abdominal ultrasonography.
Haematological parameters (RBC, Hb, MCV, MCH, MCHC,WBC, Platelet and Reticulocyte
counts) were also assessed. RESULTS: Fifty three children (35.3%) with SCA
against 19 children (12.7%)with HbAA had splenomegaly defined as spleen index >
31cm2. among the children with SCA who had splenomegaly, 17 (11.3%) were older
than 10 years. None of those above 10 years with HbAA had splenomegaly. The mean
values of RBC, Hb, MCV and MCH were significantly lower in children with SCA
compared to age- sex matched HbAA controls (p = 0.001, 0.001, 0.15 and 0.016
respectively), while the mean values of MCHC, WBC, platelet and reticulocyte
counts were significantly higher in children with SCA than in the HbAA controls
(p = 0.022, 0.001, 0.013 and 0.001) respectively. Among the SCA subjects, as
spleen index increased from grade II through grade V, the mean values of RBC, Hb,
WBC and platelet count significantly decreased (p =0.001, 0.001, 0.032 and
0.007), while the mean value of reticulocyte count significantly increased (p =
0.001). However, with increasing spleen index from grade II to grade V, the mean
values of MCV, MCH and MCHC were not significantly different (p = 0.077, 0.741
and 0.995). CONCLUSION: Splenomegaly persists in much older age group in children
with SCA and is associated with mild cytopaenia. Spleen size in children with SCA
should be assessed using a more sensitive and reliable method of ultrasonography.
PMID- 25126873
TI - Elder abuse and neglect in Zaria northern Nigeria.
AB - AIMS AND OBJECTIVES: The aim of this study was to determine the nature and extent
of elder abuse and neglect among community dwelling elderly in Zaria, Nigeria.
SUBJECTS AND METHODS: Community dwelling elderly in Zaria city North-western
Nigeria were interviewed;. they were interviewed using a data collecting sheet
designed to obtain socio-demographic data and an instrument designed to detect
abuse and neglect in the elderly. The data obtained was analysed using
Statistical Package for Social Sciences Version 13 for Windows. RESULTS: Three
hundred and fifty one elderly people participated in the study out of which
211(60.1%) were females. The mean age of the participants was 73.90 years
(95%CI=.72.96-74.84 years) There was no case of physical, financial or
psychological abuse. However, 125(35.6%) participants suffered possible neglect
in terms of personal care and hygiene. Increasing age, lack of formal education,
receiving pension, not having a spouse and self reported poor health status were
significantly associated with elder possible neglect in this community.
CONCLUSION: Elder abuse was uncommon in this community like in other communities
in the developing countries. However, possible neglect of personal care and
hygiene of the elderly was common and that might be due to poor economic status
of both the elderly and his other caregiver.
PMID- 25126874
TI - Clinical usefulness of a timed overnight (8 hours) Urine Albumin (microalbumin)
excretion in monitor-ing treatment in benign essential hypertension.
AB - AIMS AND OBJECTIVES: This research aims to establish the usefulness of timed over
night (8 hours) Urine Albumin(microalbumin) Excretion (UAE), in monitoring
therapy in Nigerian patients with benign essential hypertension. SUBJECTS AND
METHODS: The study population comprised 40 normotensives/controls, (23 males and
17 females) aged between 20-70 years, with a mean blood pressure 116/75mmHg, 30
well-controlled hypertensive patients, diastolic BP <100mmHg or MAP (mean
arterial pressure) = 110mmHg and 30 poorly controlled hypertensive patients,
diastolic blood pressure > 100mmHg or MAP >110mmHg.Urine albumin(microalbumin)
was determined on the 8 hours overnight urine samples by ELISA method using kit
from Randox Laboratories Limited, N.Ireland Cat No. MA 1410. UAE was calculated
from the urine albumin concentration, urine volume and collection time. The intra
assay precision was determined by running 20 replicates of two kit controls in a
single batch. The coefficient of variation was 6.6% at 10.70mg/L and 4.3% at
51.20mg/L. RESULTS: The average UAE in the three groups were as follows: 12:22 +/
4.65ug/ min, 21.50 +/- 10.5ug/min and 30.10 +/- 24.25 ug/min in the control, well
controlled and poorly controlled groups respectively, 12.5% of normotensive
subjects, 40% of well controlled and 56.7% of poorly controlled patients were
found to have microalbuminuria.The UAE increased significantly with the severity
of hypertension (r = 0.32, p<0.001 for control) r = 0.38, p<00.05 for controlled
and r = 0.49 p<0.05 for poorly controlled. CONCLUSION: A timed overnight (8
hours) Urinary UAE is a preferred alternative to cumbersome 24 hours urine
collection for monitoring response to treatment in Nigerian patients with benign
essential hypertension.
PMID- 25126875
TI - Implant failure in lower limb long bone diaphyseal fractures at a tertiary
hospital in Ile- Ife. Nigeria.
AB - AIMS AND OBJECTIVES: This included determining aetiology of failure and comparing
the failure rate in implant fixations using solid intramedullary nail and DCP.
PATIENTS AND METHODS: A retrospective study conducted at the Orthopaedic
Department, Obafemi Awolowo University Teaching Hospital, Ile-Ife,Nigeria.
Records of all operated cases of lower limb long bone diaphyseal fractures
including those with failed fixations from August 2006-July 2011 were reviewed.
Data retrieved included type of implant used, aetiology and characteristics of
Implant failure. Data were analysed using SPSS version 16. Frequency distribution
of the variables of interest was done. Difference in failure rate of
intramedullary nail versus DCP was tested using chi-square. Statistical
significance was inferred at p<0.05. RESULTS: A total of 280 patients were
studied out of which two hundred and twenty-one patients had long bone diaphyseal
fractures and met inclusion criteria, of which 135 had intramedullary nail
fixation and 86 had DCP. The rate of implant failure in intramedullary nail was
1.5% while it was 5.8% in patients with DCP (p=0.113; 0R=4.10; 95% CI=0.65-
43.77). Implant fracture was the commonest type of failure seen (100% versus 60%)
and non union was the commonest cause of failure seen (50% versus 40%) in the
intramedullary nailing and DCP groups respectively. CONCLUSION: The likelihood of
a failed implant is higher in fixations done with DCP compared with
intramedullary nail though the difference was not statistically significant.
Commonest reason for failure in both groups was non-union. Findings from this
study may guide surgeons in choice of implant in the management of long bone
fractures.
PMID- 25126876
TI - Polymorphisms in SPARC and coal workers' pneumoconiosis risk in a Chinese
population.
AB - BACKGROUND: The SPARC is a crucial matricellular protein and may influence the
course of various diseases like tumor metastasis and fibrosis. In the present
study, we investigated the association between the potential functional
polymorphisms in SPARC and coal workers' pneumoconiosis (CWP) risk in a Chinese
population. METHODS: Five potentially functional polymorphisms (rs1059279,
rs1059829, rs1053411, rs2304052 and rs4958281) in SPARC were genotyped and
analyzed in a case-control study including 697 CWP cases and 694 controls. The
genotyping was used by the TaqMan method with the ABI 7900HT Real Time PCR
system. RESULTS: Our results revealed that three SNPs (rs1059279, rs1059829,
rs1053411) were significantly associated with increased risk of CWP under an
additive model (OR = 1.35, 95%CI = 1.06-1.71, P = 0.015 for rs1059279; OR = 1.20,
95%CI = 1.03-1.39, P = 0.021 for rs1059829; OR = 1.31, 95%CI = 1.03-1.65, P =
0.025 for rs1053411). In the stratification analysis, significant associations
were observed between each of these three SNPs and patients with 0-20 pack-years
of smoking (OR = 1.73, 95%CI = 1.21-2.45 for rs1059279; OR = 1.48, 95%CI = 1.07
2.05 for rs105982; OR = 1.58, 95%CI = 1.13-2.22 for rs1053411). Furthermore, the
association between rs1059279 and CWP risk remained significant among subjects
with over 27 years of exposure (OR = 1.27, 95%CI = 1.03-1.56, P = 0.023). In the
combined analysis of these five polymorphisms, individuals with multiple risk
alleles had a higher risk of CWP (Ptrend = 0.015). CONCLUSION: Our results
indicate that three functional SPARC SNPs are associated with an increased risk
of CWP in a Chinese population. Further functional research and validation
studies with diverse populations are warranted to confirm our findings.
PMID- 25126878
TI - ICU physician-based determinants of life-sustaining therapy during nights and
weekends: French multicenter study from the Outcomerea Research Group.
AB - OBJECTIVE: Patient- and organization-related factors are the most common
influences affecting the ICU decision-making process. Few studies have
investigated ICU physician-related factors and life-sustaining treatment use
during nights and weekends, when staffing ratios are low. Here, we described
patients admitted during nights/weekends and looked for physician-related
determinants of life-sustaining treatment use in these patients after adjustment
for patient- and center-related factors. DESIGN: Multicenter observational cohort
study of admission procedures during nights/weekends shifts. SUBJECTS: ICU
physicians working nights/weekends in 6 French ICUs. INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Patient characteristics and intensity of care were
extracted from the prospective Outcomerea database. Physician characteristics
were age, gender, religion and religiosity, ICU experience, specialty, being a
permanent ICU staff member, degree in ethics, and degree in intensive care. We
used hierarchical mixed models to adjust on center, physician random effects, and
admission patient characteristics. Of 156 physicians contacted, 119 (77%)
participated. Patients admitted during nights/weekends were younger and had fewer
comorbidities and lower treatment intensity during the shift. ICU physicians who
are younger than 35 years used more renal replacement therapy (odds ratio, 1.04;
95% CI, 1-1.07; p = 0.04), invasive mechanical ventilation (odds ratio, 1.09; 95%
CI, 1.1-1.19; p = 0.04), and vasopressors (odds ratio, 1.16; 95% CI, 1.09-1.23; p
< 0.0001). Internal or emergency medicine as the primary specialty was associated
with invasive mechanical ventilation (odds ratio, 1.14; 95% CI, 1.04-1.24; p =
0.004) and vasopressor use (odds ratio, 1.09; 95% CI, 1.02-1.17; p = 0.01).
Noninvasive ventilation was used less often by physicians with more than 10 years
of night/weekend shifts and more often by those with religious beliefs (odds
ratio, 1.05; 95% CI, 1.01-1.08; p = 0.008). CONCLUSIONS: Patients admitted during
nights/weekends were younger and had fewer comorbidities. Age, specialty, ICU
experience, and religious beliefs of the physicians were significantly associated
life-sustaining treatments used.
PMID- 25126877
TI - Deficiency of the two-pore-domain potassium channel TREK-1 promotes hyperoxia
induced lung injury.
AB - OBJECTIVES: We previously reported the expression of the two-pore-domain K
channel TREK-1 in lung epithelial cells and proposed a role for this channel in
the regulation of alveolar epithelial cytokine secretion. In this study, we
focused on investigating the role of TREK-1 in vivo in the development of
hyperoxia-induced lung injury. DESIGN: Laboratory animal experiments. SETTING:
University research laboratory. SUBJECTS: Wild-type and TREK-1-deficient mice.
INTERVENTIONS: Mice were anesthetized and exposed to 1) room air, no mechanical
ventilation, 2) 95% hyperoxia for 24 hours, and 3) 95% hyperoxia for 24 hours
followed by mechanical ventilation for 4 hours. MEASUREMENTS AND MAIN RESULTS:
Hyperoxia exposure accentuated lung injury in TREK-1-deficient mice but not
controls, resulting in increase in lung injury scores, bronchoalveolar lavage
fluid cell numbers, and cellular apoptosis and a decrease in quasi-static lung
compliance. Exposure to a combination of hyperoxia and injurious mechanical
ventilation resulted in further morphological lung damage and increased lung
injury scores and bronchoalveolar lavage fluid cell numbers in control but not
TREK-1-deficient mice. At baseline and after hyperoxia exposure, bronchoalveolar
lavage cytokine levels were unchanged in TREK-1-deficient mice compared with
controls. Exposure to hyperoxia and mechanical ventilation resulted in an
increase in bronchoalveolar lavage interleukin-6, monocyte chemotactic protein-1,
and tumor necrosis factor-alpha levels in both mouse types, but the increase in
interleukin-6 and monocyte chemotactic protein-1 levels was less prominent in
TREK-1-deficient mice than in controls. Lung tissue macrophage inflammatory
protein-2, keratinocyte-derived cytokine, and interleukin-1beta gene expression
was not altered by hyperoxia in TREK-1-deficient mice compared with controls.
Furthermore, we show for the first time TREK-1 expression on alveolar macrophages
and unimpaired tumor necrosis factor-alpha secretion from TREK-1-deficient
macrophages. CONCLUSIONS: TREK-1 deficiency resulted in increased sensitivity of
lungs to hyperoxia, but this effect is less prominent if overwhelming injury is
induced by the combination of hyperoxia and injurious mechanical ventilation.
TREK-1 may constitute a new potential target for the development of novel
treatment strategies against hyperoxia-induced lung injury.
PMID- 25126879
TI - Early prediction of persistent organ failure by soluble CD73 in patients with
acute pancreatitis*.
AB - OBJECTIVE: New biomarkers are needed to better predict the severity of acute
pancreatitis. CD73/ecto-5'-nucleotidase is an enzyme that generates adenosine,
which dampens inflammation and improves vascular barrier function in several
disease models. CD73 also circulates in a soluble form in the blood. We studied
whether levels of soluble form of CD73 predict the development of organ failure
in acute pancreatitis. DESIGN: A prospective cohort study of patients with acute
pancreatitis from 2003 to 2007. SETTING: Admissions to the biggest tertiary care
hospital in Finland. PATIENTS: One hundred sixty-one patients with acute
pancreatitis, of which 107 were subclassified according to the revised Atlanta
criteria into mild, 29 into moderately severe and 25 into severe. INTERVENTIONS:
None. MEASUREMENTS AND MAIN RESULTS: Serum and blood cell samples were collected
at admission. Protein levels of soluble form of CD73 in serum were determined
using a novel enzyme-linked immunosorbent assay, activity of soluble form of CD73
using radioactive enzyme assays, and CD73 messenger RNA levels from leukocytes
using quantitative polymerase chain reaction. Activity and protein concentration
of soluble form of CD73, and messenger RNA level of CD73 all decreased along with
the disease severity (p <= 0.01 for all). The activity of soluble form of CD73 at
admission predicted the development of the severe pancreatitis in different
groups of the patients. The area under the receiver-operating characteristic
curve value for activity of soluble form of CD73 was 0.65 (95% CI, 0.51-0.80)
among a subgroup of patients comprising moderately severe and severe disease,
0.79 (95% CI, 0.69-0.88) among all patients including mild pancreatitis, and 0.75
(95% CI, 0.60-0.89) among patients who had no signs of organ failure (modified
Marshall score < 2) at admission. Especially, in the last-mentioned group,
activity of soluble form of CD73 was better than C-reactive protein or creatinine
in predicting the severe pancreat CONCLUSIONS: : Activity of soluble form of CD73
at admission to hospital has prognostic value in predicting the development of
the severe form of acute pancreatitis.
PMID- 25126881
TI - Environmentally benign process for the preparation of antimicrobial alpha
methylene-beta-hydroxy-gamma-butyrolactone (tulipalin B) from tulip biomass.
AB - Tulipalin B (alpha-methylene-beta-hydroxy-gamma-butyrolactone, PaB) is an
antimicrobial natural product occurring in tulip (Tulipa gesneriana). PaB is
directly formed from the precursor glucose ester 6-tuliposide B (PosB) by
endogenous Pos-converting enzyme (TCE). Despite the potential usefulness of
antibacterial PaB in various industrial applications, lack of facile synthetic
schemes hampers its practical use. Herein, we describe an environmentally benign
and facile process for the preparation of PaB using tulip biomass materials based
on one-step enzyme reaction catalyzed by TCE without the use of petroleum-derived
solvents. By screening 115 tulip cultivars, we found three elite cultivars, which
accumulated PosB almost exclusively in flower tissues. The flower extracts with
aqueous ethanol were partially purified with activated charcoal and subjected to
the enzyme reaction with reusable immobilized TCE prepared from bulb crude
extracts. The reaction was completed in a few hours at room temperature, and PaB
was purified with activated charcoal and ethanol in a batch-wise manner.
PMID- 25126883
TI - College Health's response to "not alone".
PMID- 25126880
TI - International study on microcirculatory shock occurrence in acutely ill patients.
AB - OBJECTIVES: Microcirculatory alterations are associated with adverse outcome in
subsets of critically ill patients. The prevalence and significance of
microcirculatory alterations in the general ICU population are unknown. We
studied the prevalence of microcirculatory alterations in a heterogeneous ICU
population and its predictive value in an integrative model of macro- and
microcirculatory variables. DESIGN: Multicenter observational point prevalence
study. SETTING: The Microcirculatory Shock Occurrence in Acutely ill Patients
study was conducted in 36 ICUs worldwide. PATIENTS: A heterogeneous ICU
population consisting of 501 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN
RESULTS: Demographic, hemodynamic, and laboratory data were collected in all ICU
patients who were 18 years old or older. Sublingual Sidestream Dark Field imaging
was performed to determine the prevalence of an abnormal capillary microvascular
flow index (< 2.6) and its additional value in predicting hospital mortality. In
501 patients with a median Acute Physiology and Chronic Health Evaluation II
score of 15 (10-21), a Sequential Organ Failure Assessment score of 5 (2-8), and
a hospital mortality of 28.4%, 17% exhibited an abnormal capillary microvascular
flow index. Tachycardia (heart rate > 90 beats/min) (odds ratio, 2.71; 95% CI,
1.67-4.39; p < 0.001), mean arterial pressure (odds ratio, 0.979; 95% CI, 0.963
0.996; p = 0.013), vasopressor use (odds ratio, 1.84; 95% CI, 1.11-3.07; p =
0.019), and lactate level more than 1.5 mEq/L (odds ratio, 2.15; 95% CI, 1.28
3.62; p = 0.004) were independent risk factors for hospital mortality, but not
abnormal microvascular flow index. In reference to microvascular flow index, a
significant interaction was observed with tachycardia. In patients with
tachycardia, the presence of an abnormal microvascular flow index was an
independent, additive predictor for in-hospital mortality (odds ratio, 3.24; 95%
CI, 1.30-8.06; p = 0.011). This was not true for nontachycardic patients nor for
the total group of patients. CONCLUSIONS: In a heterogeneous ICU population, an
abnormal microvascular flow index was present in 17% of patients. This was not
associated with mortality. However, in patients with tachycardia, an abnormal
microvascular flow index was independently associated with an increased risk of
hospital death.
PMID- 25126882
TI - The impact of nitration on the structure and immunogenicity of the major birch
pollen allergen Bet v 1.0101.
AB - Allergy prevalence has increased in industrialized countries. One contributing
factor could be pollution, which can cause nitration of allergens exogenously (in
the air) or endogenously (in inflamed lung tissue). We investigated the impact of
nitration on both the structural and immunological behavior of the major birch
pollen allergen Bet v 1.0101 to determine whether nitration might be a factor in
the increased incidence of allergy. Bet v 1.0101 was nitrated with
tetranitromethane. Immune effects were assessed by measuring the proliferation of
specific T-cell lines (TCLs) upon stimulation with different concentrations of
nitrated and unmodified allergen, and by measurement of cytokine release of
monocyte-derived dendritic cells (moDCs) and primary DCs (primDCs) stimulated
with nitrated versus unmodified allergen. HPLC-MS, crystallography, gel
electrophoresis, amino acid analysis, size exclusion chromatography and molecular
dynamics simulation were performed to characterize structural changes after
nitration of the allergen. The proliferation of specific TCLs was higher upon
stimulation with the nitrated allergen in comparison to the unmodified allergen.
An important structural consequence of nitration was oligomerization. Moreover,
analysis of the crystal structure of nitrated Bet v 1.0101 showed that amino acid
residue Y83, located in the hydrophobic cavity, was nitrated to 100%. Both moDCs
and primDCs showed decreased production of TH1-priming cytokines, thus favoring a
TH2 response. These results implicate that nitration of Bet v 1.0101 might be a
contributing factor to the observed increase in birch pollen allergy, and
emphasize the importance of protein modifications in understanding the molecular
basis of allergenicity.
PMID- 25126884
TI - Evelyn Wiener.
PMID- 25126885
TI - Comparison of skin and soft tissue infections caused by Vibrio and Aeromonas
species.
AB - BACKGROUND: The aim of this study was to compare skin and soft tissue infections
(SSTIs) caused by Vibrio and Aeromonas spp. METHODS: Patients whose cultures
yielded Vibrio or Aeromonas spp. from July 2004 to June 2010 were retrieved from
the computerized database of the bacteriology laboratory at a hospital in
southern Taiwan. The medical records were reviewed for all patients fulfilling
the criteria of monomicrobial Vibrio or Aeromonas spp. SSTIs and the clinical
characteristics were analyzed. RESULTS: During the study period, there were 28
patients with Vibrio spp. and 26 patients with Aeromonas spp., respectively.
Vibrio vulnificus (n=25) and A. hydrophila (n=14) were the most common spp. There
were no significant differences in age, gender, underlying diseases between
patients with Vibrio and Aeromonas SSTIs. In comparison to Aeromonas SSTIs, more
patients with Vibrio SSTIs were complicated with acute respiratory failure (39.3%
vs. 3.8%, p=0.002) and required intensive care unit admission (50.0% vs. 7.7%,
p<0.001). Furthermore, patients with Aeromonas SSTIs had a higher likelihood of
discharge alone within 30 days than Vibrio SSTIs (p=0.049). The difference in in
hospital mortality among the two groups was not statistically significant
(p=0.11). CONCLUSION: Both Aeromonas and Vibrio spp. cause SSTIs in southern
Taiwan and the pathogenicity of Vibrio spp. might be higher than Aeromonas spp.
PMID- 25126886
TI - Production and partial purification of tannase from Aspergillus ficuum Gim 3.6.
AB - A novel fungal strain, Aspergillus ficuum Gim 3.6, was evaluated for its tannase
producing capability in a wheat bran-based solid-state fermentation. Thin-layer
chromatography (TLC) analysis revealed that the strain was able to degrade tannic
acid to gallic acid and pyrogallol during the fermentation process. Quantitation
of enzyme activity demonstrated that this strain was capable of producing a
relatively high yield of extracellular tannase. Single-factor optimization of
process parameters resulted in high yield of tannase after 60 hr of incubation at
a pH of 5.0 at 30 degrees C, 1 mL of inoculum size, and 1:1 solid-liquid ratio in
the presence of 2.0% (w/v) tannic acid as inducer. The potential of aqueous two
phase extraction (ATPE) for the purification of tannase was investigated.
Influence of various parameters such as phase-forming salt, molecular weight of
polyethylene glycol (PEG), pH, and stability ratio on tannase partition and
purification was studied. In all the systems, the target enzyme was observed to
preferentially partition to the PEG-rich top phase, and the best result of
purification (2.74-fold) with an enzyme activity recovery of 77.17% was obtained
in the system containing 17% (w/w) sodium citrate and 18.18% (w/w) PEG1000, at pH
7.0.
PMID- 25126887
TI - Growth kinetics and growth mechanism of ultrahigh mass density carbon nanotube
forests on conductive Ti/Cu supports.
AB - We evaluate the growth kinetics and growth mechanism of ultrahigh mass density
carbon nanotube forests. They are synthesized by chemical vapor deposition at 450
degrees C using a conductive Ti/Cu support and Co-Mo catalyst system. We find
that Mo stabilizes Co particles preventing lift off during the initial growth
stage, thus promoting the growth of ultrahigh mass density nanotube forests by
the base growth mechanism. The morphology of the forest gradually changes with
growth time, mostly because of a structural change of the catalyst particles.
After 100 min growth, toward the bottom of the forest, the area density decreases
from ~ 3-6 * 10(11) cm(-2) to ~ 5 * 10(10) cm(-2) and the mass density decreases
from 1.6 to 0.38 g cm(-3). We also observe part of catalyst particles detached
and embedded within nanotubes. The progressive detachment of catalyst particles
results in the depletion of the catalyst metals on the substrate surfaces. This
is one of the crucial reasons for growth termination and may apply to other
catalyst systems where the same features are observed. Using the packed forest
morphology, we demonstrate patterned forest growth with a pitch of ~ 300 nm and a
line width of ~ 150 nm. This is one of the smallest patterning of the carbon
nanotube forests to date.
PMID- 25126888
TI - Effects of a brief school-based media literacy intervention on digital media use
in adolescents: cluster randomized controlled trial.
AB - The aim of this study was to evaluate the effects of a four-session school-based
media literacy curriculum on adolescent computer gaming and Internet use
behavior. The study comprised a cluster randomized controlled trial with three
assessments (baseline, posttest, and 12-month follow-up). At baseline, a total of
2,303 sixth and seventh grade adolescents from 27 secondary schools were
assessed. Of these, 1,843 (80%) could be reached at all three assessments
(Mage=12.0 years; SD=0.83). Students of the intervention group received the media
literacy program Vernetzte www.Welten ("Connected www.Worlds ") implemented by
trained teachers during class time. The control group attended regular class.
Main outcome measures were adolescents' computer gaming and Internet use: days
per month, hours per day, and addictive use patterns. Parental media monitoring
and rules at home were assessed as secondary outcomes. Results of multilevel
growth-curve models revealed a significant intervention effect in terms of a
lower increase in self-reported gaming frequency (beta = -1.10 [95% CI -2.06,
0.13]), gaming time (beta = -0.27 [95% CI -0.40, -0.14]), and proportion of
excessive gamers (AOR=0.21 [95% CI 0.08, 0.57]) in the intervention group. There
were also significant group-time interactions for the addictive gaming scale
(beta=-0.08 [95% CI -0.12, -0.04]), and the Internet Addiction Scale (beta =
0.06 [95% CI -0.10, -0.01]). No effect was found for days and hours of Internet
use or parental media behavior. The study shows that the program Vernetzte
www.Welten can influence adolescents' media use behavior. Future research should
address mediating and moderating variables of program effects.
PMID- 25126889
TI - Synthesis, biological evaluation, and molecular modeling of new 3
(cyclopentyloxy)-4-methoxybenzaldehyde O-(2-(2,6-dimethylmorpholino)-2-oxoethyl)
Oxime (GEBR-7b) related phosphodiesterase 4D (PDE4D) inhibitors.
AB - A new series of 3-(cyclopentyloxy)-4-methoxyphenyl derivatives, structurally
related to our hit GEBR-4a (1) and GEBR-7b (2), has been designed by changing
length and functionality of the chain linking the catecholic moiety to the
terminal cycloamine portion. Among the numerous molecules synthesized, compounds
8, 10a, and 10b showed increased potency as PDE4D enzyme inhibitors with respect
to 2 and a good selectivity against PDE4A4, PDE4B2, and PDE4C2 enzymes, without
both cytotoxic and genotoxic effects. The ability to enhance cAMP level in
neuronal cells was assessed for compound 8. SAR considerations, also confirmed by
in silico docking simulations, evidenced that both chain and amino terminal
function characterized by higher hydrophilicity are required for a good and
selective inhibitor-catalytic pocket interaction.
PMID- 25126890
TI - IWBDA 2013.
PMID- 25126893
TI - PR-PR: cross-platform laboratory automation system.
AB - To enable protocol standardization, sharing, and efficient implementation across
laboratory automation platforms, we have further developed the PR-PR open-source
high-level biology-friendly robot programming language as a cross-platform
laboratory automation system. Beyond liquid-handling robotics, PR-PR now supports
microfluidic and microscopy platforms, as well as protocol translation into human
languages, such as English. While the same set of basic PR-PR commands and
features are available for each supported platform, the underlying optimization
and translation modules vary from platform to platform. Here, we describe these
further developments to PR-PR, and demonstrate the experimental implementation
and validation of PR-PR protocols for combinatorial modified Golden Gate DNA
assembly across liquid-handling robotic, microfluidic, and manual platforms. To
further test PR-PR cross-platform performance, we then implement and assess PR-PR
protocols for Kunkel DNA mutagenesis and hierarchical Gibson DNA assembly for
microfluidic and manual platforms.
PMID- 25126894
TI - Chiral gold nanowires with Boerdijk-Coxeter-Bernal structure.
AB - A Boerdijk-Coxeter-Bernal (BCB) helix is made of linearly stacked regular
tetrahedra (tetrahelix). As such, it is chiral without nontrivial translational
or rotational symmetries. We demonstrate here an example of the chiral BCB
structure made of totally symmetrical gold atoms, created in nanowires by direct
chemical synthesis. Detailed study by high-resolution electron microscopy
illustrates their elegant chiral structure and the unique one-dimensional "pseudo
periodicity". The BCB-type atomic packing mode is proposed to be a result of the
competition and compromise between the lattice and surface energy.
PMID- 25126895
TI - Identification and mitigation of a reactive metabolite liability associated with
aminoimidazoles.
AB - Reactive metabolites (RMs) have been implicated as causal factors in many drug
associated idiosyncratic toxicities. This study aims at identification and
mitigation of an RM liability associated with aminoimidazole and
amino(aza)benzimidazole structural motifs from an antimalarial project. Nineteen
compounds with different structural modifications were studied in rat and human
liver microsomes using glutathione (GSH) and N-acetyl cysteine (NAC) as trapping
agents for RM. Metabolite profiling of aminoimidazole compounds in initial
studies revealed the presence of dihydrodiol metabolites suggestive of reactive
epoxide precursors, confirmed by the identification of a dihydrohydroxy GSH
conjugate in GSH supplemented incubations. Substitution of methyl group at a
potential site of metabolism blocked the epoxidation; however, formation of an
imine-methide RM was suspected. Masking the site of metabolism via benzimidazole
and 4/7-azabenzimidazole resulted in the possible formation of quinone-imine
intermediates as a product of bioactivation. Further, substitutions with electron
withdrawing groups and steric crowding did not address this liability. Mitigation
of bioactivation was achieved with 5/6-azabenzimidazole and with CF3 substitution
at the 6-position of the 7-azabenzimidazole ring. Moreover, compounds devoid of
imidazole -NH2 do not undergo bioactivation. This study, therefore, establishes
aminoimidazole and amino(aza)benzimidazoles as potential toxicophores and
describes ways to mitigate this bioactivation liability by chemical modification.
PMID- 25126897
TI - Size-resolved deposition rates for ultrafine and submicrometer particles in a
residential housing unit.
AB - We estimated the size-resolved particle deposition rates for the ultrafine and
submicrometer particles using a nonlinear regression method with unknown particle
background concentrations during nonsourced period following a controlled sourced
period in a well-mixed residential environment. A dynamic adjustment method in
conjunction with the constant injection of tracer gas was used to maintain the
air exchange rate at three target levels across the range of 0.61-1.24 air change
per hour (ACH). Particle deposition was found to be highly size dependent with
rates ranging from 0.68 +/- 0.10 to 5.03 +/- 0.20 h(-1) (mean +/- s.e.). Our
findings also suggest that the effect of air exchange on the particle deposition
under enhanced air mixing was relatively small when compared to both the strong
influence of size-dependent deposition mechanisms and the effects of mechanical
air mixing by fans. Nonetheless, the significant association between air exchange
and particle deposition rates for a few size categories indicated potential
influence of air exchange on particle deposition. In the future, the proposed
approach can be used to explore the separate or composite effects between air
exchange and air mixing on particle deposition rates, which will contribute to
improved assessment of human exposure to ultrafine and submicrometer particles.
PMID- 25126896
TI - Labeled EF-Tus for rapid kinetic studies of pretranslocation complex formation.
AB - The universally conserved translation elongation factor EF-Tu delivers
aminoacyl(aa)-tRNA in the form of an aa-tRNA.EF-Tu.GTP ternary complex (TC) to
the ribosome where it binds to the cognate mRNA codon within the ribosomal A
site, leading to formation of a pretranslocation (PRE) complex. Here we describe
preparation of QSY9 and Cy5 derivatives of the variant E348C-EF-Tu that are
functional in translation elongation. Together with fluorophore derivatives of aa
tRNA and of ribosomal protein L11, located within the GTPase associated center
(GAC), these labeled EF-Tus allow development of two new FRET assays that permit
the dynamics of distance changes between EF-Tu and both L11 (Tu-L11 assay) and aa
tRNA (Tu-tRNA assay) to be determined during the decoding process. We use these
assays to examine: (i) the relative rates of EF-Tu movement away from the GAC and
from aa-tRNA during decoding, (ii) the effects of the misreading-inducing
antibiotics streptomycin and paromomycin on tRNA selection at the A-site, and
(iii) how strengthening the binding of aa-tRNA to EF-Tu affects the rate of EF-Tu
movement away from L11 on the ribosome. These FRET assays have the potential to
be adapted for high throughput screening of ribosomal antibiotics.
PMID- 25126898
TI - Large negatively charged organic host molecules as inhibitors of endonuclease
enzymes.
AB - Three large negatively charged organic host molecules; beta-cyclodextrin
sulphate, para-sulphonato-calix[6]arene and para-sulphonato-calix[8]arene have
been shown to be effective inhibitors of endonuclease in the low micromolar
range, additionally para-sulphonato-calix[8]arene is a partial inhibitor of
rhDNase I.
PMID- 25126899
TI - Colorectal cancer detection using targeted serum metabolic profiling.
AB - Colorectal cancer (CRC) is one of the most prevalent and deadly cancers in the
world. Despite an expanding knowledge of its molecular pathogenesis during the
past two decades, robust biomarkers to enable screening, surveillance, and
therapy monitoring of CRC are still lacking. In this study, we present a targeted
liquid chromatography-tandem mass spectrometry-based metabolic profiling approach
for identifying biomarker candidates that could enable highly sensitive and
specific CRC detection using human serum samples. In this targeted approach, 158
metabolites from 25 metabolic pathways of potential significance were monitored
in 234 serum samples from three groups of patients (66 CRC patients, 76 polyp
patients, and 92 healthy controls). Partial least-squares-discriminant analysis
(PLS-DA) models were established, which proved to be powerful for distinguishing
CRC patients from both healthy controls and polyp patients. Receiver operating
characteristic curves generated based on these PLS-DA models showed high
sensitivities (0.96 and 0.89, respectively, for differentiating CRC patients from
healthy controls or polyp patients), good specificities (0.80 and 0.88), and
excellent areas under the curve (0.93 and 0.95). Monte Carlo cross validation was
also applied, demonstrating the robust diagnostic power of this metabolic
profiling approach.
PMID- 25126900
TI - Salt effects on lamellar repeat distance depending on head groups of neutrally
charged lipids.
AB - Change in lamellar repeat distances of neutrally charged lipids upon addition of
monovalent salts was measured with small-angle X-ray scattering for combinations
of two lipids (PC and PE lipids) and six salts. Large dependence on lipid head
group is observed in addition to those on added cation and anion. The ion and
lipid dependences have little correlation with measured surface potentials of
lipid membranes. These results indicate that the lamellar swelling by salt is not
explained through balance among interactions considered previously (van der Waals
interaction, electrostatic repulsion emerged by ion binding, etc.). It is
suggested that effect of water structure, which is affected by not only ions but
also lipid itself, should be taken into account for understanding membrane
membrane interactions, as in the Hofmeister effect.
PMID- 25126901
TI - Temporal quantum correlations and Leggett-Garg inequalities in multilevel
systems.
AB - We show that the quantum bound for temporal correlations in a Leggett-Garg test,
analogous to the Tsirelson bound for spatial correlations in a Bell test,
strongly depends on the number of levels N that can be accessed by the
measurement apparatus via projective measurements. We provide exact bounds for
small N that exceed the known bound for the Leggett-Garg inequality, and we show
that in the limit N->infinity the Leggett-Garg inequality can be violated up to
its algebraic maximum.
PMID- 25126902
TI - Measuring a topological transition in an artificial spin-1/2 system.
AB - We present measurements of a topological property, the Chern number (C_{1}), of a
closed manifold in the space of two-level system Hamiltonians, where the two
level system is formed from a superconducting qubit. We manipulate the parameters
of the Hamiltonian of the superconducting qubit along paths in the manifold and
extract C_{1} from the nonadiabatic response of the qubit. By adjusting the
manifold such that a degeneracy in the Hamiltonian passes from inside to outside
the manifold, we observe a topological transition C_{1}=1->0. Our measurement of
C_{1} is quantized to within 2% on either side of the transition.
PMID- 25126903
TI - Invariants of broken discrete symmetries.
AB - The parity and Bloch theorems are generalized to the case of broken global
symmetry. Local inversion or translation symmetries in one dimension are shown to
yield invariant currents that characterize wave propagation. These currents map
the wave function from an arbitrary spatial domain to any symmetry-related
domain. Our approach addresses any combination of local symmetries, thus
applying, in particular, to acoustic, optical, and matter waves. Nonvanishing
values of the invariant currents provide a systematic pathway to the breaking of
discrete global symmetries.
PMID- 25126904
TI - Steering bound entangled States: a counterexample to the stronger Peres
conjecture.
AB - Quantum correlations are at the heart of many applications in quantum information
science and, at the same time, they form the basis for discussions about genuine
quantum effects and their difference to classical physics. On one hand,
entanglement theory provides the tools to quantify correlations in information
processing and many results have been obtained to discriminate useful
entanglement, which can be distilled to a pure form, from bound entanglement,
being of limited use in many applications. On the other hand, for discriminating
quantum phenomena from their classical counterparts, Schrodinger and Bell
introduced the notions of steering and local hidden variable models. We provide a
method to generate systematically bound entangled quantum states which can still
be used for steering and, therefore, to rule out local hidden state models. This
sheds light on the relations between the various views on quantum correlations
and disproves a widespread conjecture known as the stronger Peres conjecture. For
practical applications, it implies that even the weakest form of entanglement can
be certified in a semidevice independent way.
PMID- 25126905
TI - Many-body interactions with tunable-coupling transmon qubits.
AB - The efficient implementation of many-body interactions in superconducting
circuits allows for the realization of multipartite entanglement and topological
codes, as well as the efficient simulation of highly correlated fermionic
systems. We propose the engineering of fast multiqubit interactions with tunable
transmon-resonator couplings. This dynamics is obtained by the modulation of
magnetic fluxes threading superconducting quantum interference device loops
embedded in the transmon devices. We consider the feasibility of the proposed
implementation in a realistic scenario and discuss potential applications.
PMID- 25126906
TI - Nonequilibrium dynamics of one-dimensional hard-core anyons following a quench:
complete relaxation of one-body observables.
AB - We demonstrate the role of interactions in driving the relaxation of an isolated
integrable quantum system following a sudden quench. We consider a family of
integrable hard-core lattice anyon models that continuously interpolates between
noninteracting spinless fermions and strongly interacting hard-core bosons. A
generalized Jordan-Wigner transformation maps the entire family to noninteracting
fermions. We find that, aside from the singular free-fermion limit, the entire
single-particle density matrix and, therefore, all one-body observables relax to
the predictions of the generalized Gibbs ensemble (GGE). This demonstrates that,
in the presence of interactions, correlations between particles in the many-body
wave function provide the effective dissipation required to drive the relaxation
of all one-body observables to the GGE. This relaxation does not depend on
translational invariance or the tracing out of any spatial domain of the system.
PMID- 25126907
TI - Naturalness and the weak gravity conjecture.
AB - The weak gravity conjecture (WGC) is an ultraviolet consistency condition
asserting that an Abelian force requires a state of charge q and mass m with
q>m/m_{Pl}. We generalize the WGC to product gauge groups and study its tension
with the naturalness principle for a charged scalar coupled to gravity.
Reconciling naturalness with the WGC either requires a Higgs phase or a low
cutoff at Lambda~qm_{Pl}. If neither applies, one can construct simple models
that forbid a natural electroweak scale and whose observation would rule out the
naturalness principle.
PMID- 25126908
TI - Relative entropies in conformal field theory.
AB - Relative entropy is a measure of distinguishability for quantum states, and it
plays a central role in quantum information theory. The family of Renyi entropies
generalizes to Renyi relative entropies that include, as special cases, most
entropy measures used in quantum information theory. We construct a Euclidean
path-integral approach to Renyi relative entropies in conformal field theory,
then compute the fidelity and the relative entropy of states in one spatial
dimension at zero and finite temperature using a replica trick. In contrast to
the entanglement entropy, the relative entropy is free of ultraviolet
divergences, and is obtained as a limit of certain correlation functions. The
relative entropy of two states provides an upper bound on their trace distance.
PMID- 25126909
TI - Radiative electroweak symmetry breaking model perturbative all the way to the
Planck scale.
AB - We discuss an extension of the standard model by fields not charged under
standard model gauge symmetry in which the electroweak symmetry breaking is
driven by the Higgs quartic coupling itself without the need for a negative mass
term in the potential. This is achieved by a scalar field S with a large coupling
to the Higgs field at the electroweak scale which is driven to very small values
at high energies by the gauge coupling of a hidden symmetry under which S is
charged. This model can remain perturbative all the way to the Planck scale. The
Higgs boson is fully standard-model-like in its couplings to fermions and gauge
bosons. However, the effective cubic and quartic self-couplings of the Higgs
boson are significantly enhanced.
PMID- 25126910
TI - Freeze-out parameters from electric charge and baryon number fluctuations: is
there consistency?
AB - Recent results for moments of multiplicity distributions of net protons and net
electric charge from the STAR Collaboration are compared to lattice QCD results
for higher order fluctuations of baryon number and electric charge by the
Wuppertal-Budapest Collaboration, with the purpose of extracting the freeze-out
temperature and chemical potential. All lattice simulations are performed for a
system of 2+1 dynamical quark flavors, at the physical mass for light and strange
quarks; all results are continuum extrapolated. We show that it is possible to
extract an upper value for the freeze-out temperature, as well as precise
baryochemical potential values corresponding to the four highest collision
energies of the experimental beam energy scan. Consistency between the freeze-out
parameters obtained from baryon number and electric charge fluctuations is found.
The freeze-out chemical potentials are now in agreement with the statistical
hadronization model.
PMID- 25126912
TI - Neutron pair transfer in (60)Ni+(116)Sn far below the Coulomb barrier.
AB - An excitation function of one- and two-neutron transfer channels for the
^{60}Ni+^{116}Sn system has been measured with the magnetic spectrometer PRISMA
in a wide energy range, from the Coulomb barrier to far below it. The
experimental transfer probabilities are well reproduced, for the first time with
heavy ions, in absolute values and in slope by microscopic calculations which
incorporate nucleon-nucleon pairing correlations.
PMID- 25126913
TI - Proton-neutron pairing correlations in the self-conjugate nucleus (38)K probed
via a direct measurement of the isomer shift.
AB - A marked difference in the nuclear charge radius was observed between the
I^{pi}=3^{+} ground state and the I^{pi}=0^{+} isomer of ^{38}K and is
qualitatively explained using an intuitive picture of proton-neutron pairing. In
a high-precision measurement of the isomer shift using bunched-beam collinear
laser spectroscopy at CERN-ISOLDE, a change in the mean-square charge radius of
?r_{c}^{2}?(^{38}K^{m})-?r_{c}^{2}?(^{38}K^{g})=0.100(6) fm^{2} was obtained.
This is an order of magnitude more accurate than the result of a previous
indirect measurement from which it was concluded that both long-lived states in
^{38}K have similar charge radii. Our observation leads to a substantially
different understanding since the difference in charge radius is, moreover,
opposite in sign to previously reported theoretical predictions. It is
demonstrated that the observed isomer shift can be reproduced by large-scale
shell-model calculations including proton and neutron excitations across the
N,Z=20 shell gaps, confirming the significance of cross-shell correlations in the
region of ^{40}Ca.
PMID- 25126914
TI - Entanglement generation using discrete solitons in Coulomb crystals.
AB - Laser-cooled and trapped ions can crystallize and feature discrete solitons that
are nonlinear, topologically protected configurations of the Coulomb crystal.
Such solitons, as their continuum counterparts, can move within the crystal,
while their discreteness leads to the existence of a gap-separated, spatially
localized motional mode of oscillation above the spectrum. Suggesting that these
unique properties of discrete solitons can be used for generating entanglement
between different sites of the crystal, we study a detailed proposal in the
context of state-of-the-art experimental techniques. We analyze the interaction
of periodically driven planar ion crystals with optical forces, revealing the
effects of micromotion in radio-frequency traps inherent to such structures, as
opposed to linear ion chains. The proposed method requires Doppler cooling of the
crystal and sideband cooling of the soliton's localized modes alone. Since the
gap separation of the latter is nearly independent of the crystal size, this
approach could be particularly useful for producing entanglement and studying
system-environment interactions in large, two- and possibly three-dimensional
systems.
PMID- 25126915
TI - Deexcitation dynamics of superhydrogenated polycyclic aromatic hydrocarbon
cations after soft-x-ray absorption.
AB - We have investigated the response of superhydrogenated gas-phase coronene cations
upon soft x-ray absorption. Carbon (1s)?pi^{?} transitions were resonantly
excited at hnu=285 eV. The resulting core hole is then filled in an Auger decay
process, with the excess energy being released in the form of an Auger electron.
Predominantly highly excited dications are thus formed, which cool down by
hydrogen emission. In superhydrogenated systems, the additional H atoms act as a
buffer, quenching loss of native H atoms and molecular fragmentation.
Dissociation and transition state energies for several H loss channels were
computed by means of density functional theory. Using these energies as input
into an Arrhenius-type cascade model, very good agreement with the experimental
data is found. The results have important implications for the survival of
polyaromatic hydrocarbons in the interstellar medium and reflect key aspects of
graphene hydrogenation.
PMID- 25126917
TI - Three-body recombination at vanishing scattering lengths in an ultracold bose
gas.
AB - We report on measurements of three-body recombination loss rates in an ultracold
gas of ^{7}Li atoms in the extremely nonuniversal regime where the two-body
scattering length vanishes. We show that the loss rate coefficient is well
defined and can be described by two-body parameters only: the scattering length a
and the effective range R_{e}. We find the rate to be energy independent, and, by
connecting our results with previously reported measurements in the universal
limit, we cover the behavior of the three-body recombination rate in the whole
range from weak to strong two-body interactions. We identify a nontrivial
magnetic field value in the nonuniversal regime where the rate should be
suppressed.
PMID- 25126916
TI - Eley-rideal reactions with N atoms at Ru(0001): formation of NO and N(2).
AB - Forward-directed NO molecules with large translational energies are formed upon
exposure of an O-covered Ru(0001) surface to a nitrogen (N+N_{2}) beam. This is
an unequivocal experimental demonstration of the Eley-Rideal reaction for a
"heavy" (i.e., nonhydrogenated) neutral system. The time dependence of prompt NO
formation exhibits an exceptionally fast decay as a consequence of shifting
reaction pathways and probabilities over the course of the exposure. Prompt
production shuts down as the O coverage decreases due to competition from more
favorable Eley-Rideal production of N_{2}.
PMID- 25126918
TI - Single-photon transistor mediated by interstate Rydberg interactions.
AB - We report on the realization of an all-optical transistor by mapping gate and
source photons into strongly interacting Rydberg excitations with different
principal quantum numbers in an ultracold atomic ensemble. We obtain a record
switch contrast of 40% for a coherent gate input with mean photon number one and
demonstrate attenuation of source transmission by over ten photons with a single
gate photon. We use our optical transistor to demonstrate the nondestructive
detection of a single Rydberg atom with a fidelity of 0.72(4).
PMID- 25126919
TI - Single-photon transistor using a Forster resonance.
AB - An all-optical transistor is a device in which a gate light pulse switches the
transmission of a target light pulse with a gain above unity. The gain quantifies
the change of the transmitted target photon number per incoming gate photon. We
study the quantum limit of one incoming gate photon and observe a gain of 20. The
gate pulse is stored as a Rydberg excitation in an ultracold gas. The
transmission of the subsequent target pulse is suppressed by Rydberg blockade,
which is enhanced by a Forster resonance. The detected target photons reveal in a
single shot with a fidelity above 0.86 whether a Rydberg excitation was created
during the gate pulse. The gain offers the possibility to distribute the
transistor output to the inputs of many transistors, thus making complex
computational tasks possible.
PMID- 25126920
TI - Spectral multiplexing for scalable quantum photonics using an atomic frequency
comb quantum memory and feed-forward control.
AB - Future multiphoton applications of quantum optics and quantum information science
require quantum memories that simultaneously store many photon states, each
encoded into a different optical mode, and enable one to select the mapping
between any input and a specific retrieved mode during storage. Here we show,
with the example of a quantum repeater, how to employ spectrally multiplexed
states and memories with fixed storage times that allow such mapping between
spectral modes. Furthermore, using a Ti:Tm:LiNbO_{3} waveguide cooled to 3 K, a
phase modulator, and a spectral filter, we demonstrate storage followed by the
required feed-forward-controlled frequency manipulation with time-bin qubits
encoded into up to 26 multiplexed spectral modes and 97% fidelity.
PMID- 25126921
TI - PT-symmetric phonon laser.
AB - By exploiting recent developments associated with coupled microcavities, we
introduce the concept of the PT-symmetric phonon laser with balanced gain and
loss. This is accomplished by introducing gain to one of the microcavities such
that it balances the passive loss of the other. In the vicinity of the gain-loss
balance, a strong nonlinear relation emerges between the intracavity-photon
intensity and the input power. This then leads to a giant enhancement of both
optical pressure and mechanical gain, resulting in a highly efficient phonon
lasing action. These results provide a promising approach for manipulating
optomechanical systems through PT-symmetric concepts. Potential applications
range from enhancing mechanical cooling to designing phonon-laser amplifiers.
PMID- 25126922
TI - Universality of tip singularity formation in freezing water drops.
AB - A drop of water deposited on a cold plate freezes into an ice drop with a pointy
tip. While this phenomenon clearly finds its origin in the expansion of water
upon freezing, a quantitative description of the tip singularity has remained
elusive. Here we demonstrate how the geometry of the freezing front, determined
by heat transfer considerations, is crucial for the tip formation. We perform
systematic measurements of the angles of the conical tip, and reveal the dynamics
of the solidification front in a Hele-Shaw geometry. It is found that the cone
angle is independent of substrate temperature and wetting angle, suggesting a
universal, self-similar mechanism that does not depend on the rate of
solidification. We propose a model for the freezing front and derive resulting
tip angles analytically, in good agreement with the experiments.
PMID- 25126923
TI - Time-reversal-symmetry breaking in turbulence.
AB - In three-dimensional turbulent flows, the flux of energy from large to small
scales breaks time symmetry. We show here that this irreversibility can be
quantified by following the relative motion of several Lagrangian tracers. We
find by analytical calculation, numerical analysis, and experimental observation
that the existence of the energy flux implies that, at short times, two particles
separate temporally slower forwards than backwards, and the difference between
forward and backward dispersion grows as t^{3}. We also find the geometric
deformation of material volumes, defined by four points spanning an initially
regular tetrahedron, to show sensitivity to the time reversal with an effect
growing linearly in t. We associate this with the structure of the strain rate in
the flow.
PMID- 25126924
TI - Entropy- and flow-induced superfluid states.
AB - Normally the role of phase fluctuations in superfluids and superconductors is to
drive a phase transition to the normal state. This happens due to proliferation
of topologically nontrivial phase fluctuations in the form of vortices. Here we
discuss a class of systems where, by contrast, nontopological phase fluctuations
can produce superfluidity. Here we understand superfluidity as a phenomenon that
does not necessarily arises from a broken U(1) symmetry, but can be associated
with a certain class of (approximate or exact) degeneracies of the system's
energy landscape giving raise to a U(1)-like phase.
PMID- 25126925
TI - Anomalous behavior of dark states in quantum gases of (6)Li.
AB - We create atom-molecule dark states in a degenerate Fermi gas of ^{6}Li in both
weakly and strongly interacting regimes using two-photon Raman scattering to
couple fermion pairs to bound molecular states in the ground singlet and triplet
potential. Near the unitarity point in the BEC-BCS crossover regime, the atom
number revival height associated with the dark state abruptly and unexpectedly
decreases and remains low for magnetic fields below the Feshbach resonance center
at 832.2 G. With a weakly interacting Fermi gas at 0 G, we perform precision dark
state spectroscopy of the least-bound vibrational levels of the lowest singlet
and triplet potentials. From these spectra, we obtain binding energies of the
v^{''}=9, N^{''}=0 level of the a(1^{3}Sigma_{u}^{+}) potential and the
v^{''}=38, N^{''}=0 level of the X(1^{1}Sigma_{g}^{+}) potential with absolute
uncertainty as low as 20 kHz. For the triplet potential, we resolve the molecular
hyperfine structure.
PMID- 25126926
TI - Jumping-catalyst dynamics in nanowire growth.
AB - Nanowire growth is generally considered a steady-state process, but oscillatory
phenomena are known to often play a fundamental role. Here we identify a natural
sequence of distinct growth modes, in two of which the catalyst droplet jumps
periodically on and off a crystal facet. The oscillatory modes result from a
mismatch between catalyst size and wire diameter; they enable growth of straight
smooth-sided wires even when the droplet is too small to span the wire tip.
Jumping-catalyst growth modes are seen both in computer simulations of vapor
liquid-solid growth, and in movies of Si nanowire growth obtained by in situ
microscopy. Our simulations also provide new insight into nanowire kinking.
PMID- 25126927
TI - Phase-resolved surface plasmon interferometry of graphene.
AB - The surface plasmon polaritons (SPPs) of graphene reflect the microscopic spatial
variations of underlying electronic structure and dynamics. Here, we excite and
image the graphene SPP response in phase and amplitude by near-field
interferometry. We develop an analytic cavity model that can self-consistently
describe the SPP response function for edge, grain boundary, and defect SPP
reflection and scattering. The derived SPP wave vector, damping, and carrier
mobility agree with the results from more complex models. Spatial variations in
the Fermi level and associated variations in dopant concentration reveal a
nanoscale spatial inhomogeneity in the reduced conductivity at internal
boundaries. The additional SPP phase information thus opens a new degree of
freedom for spatial and spectral graphene SPP tuning and modulation for
optoelectronics applications.
PMID- 25126928
TI - Role of dispersion interactions in the polymorphism and entropic stabilization of
the aspirin crystal.
AB - Aspirin has been used and studied for over a century but has only recently been
shown to have an additional polymorphic form, known as form II. Since the two
observed solid forms of aspirin are degenerate in terms of lattice energy,
kinetic effects have been suggested to determine the metastability of the less
abundant form II. Here, first-principles calculations provide an alternative
explanation based on free-energy differences at room temperature. The explicit
consideration of many-body van der Waals interactions in the free energy
demonstrates that the stability of the most abundant form of aspirin is due to a
subtle coupling between collective electronic fluctuations and quantized lattice
vibrations. In addition, a systematic analysis of the elastic properties of the
two forms of aspirin rules out mechanical instability of form II as making it
metastable.
PMID- 25126929
TI - Semiconducting-to-metallic photoconductivity crossover and temperature-dependent
Drude weight in graphene.
AB - We investigate the transient photoconductivity of graphene at various gate-tuned
carrier densities by optical-pump terahertz-probe spectroscopy. We demonstrate
that graphene exhibits semiconducting positive photoconductivity near zero
carrier density, which crosses over to metallic negative photoconductivity at
high carrier density. These observations can be accounted for by the interplay
between photoinduced changes of both the Drude weight and carrier scattering
rate. Our findings provide a complete picture to explain the opposite
photoconductivity behavior reported in (undoped) graphene grown epitaxially and
(doped) graphene grown by chemical vapor deposition. Notably, we observe
nonmonotonic fluence dependence of the photoconductivity at low carrier density.
This behavior reveals the nonmonotonic temperature dependence of the Drude weight
in graphene, a unique property of two-dimensional massless Dirac fermions.
PMID- 25126931
TI - Negative oxygen isotope effect on the static spin stripe order in superconducting
La(2-x)Ba(x)CuO(4) (x=1/8) observed by muon-spin rotation.
AB - Large negative oxygen-isotope (^{16}O and ^{18}O) effects (OIEs) on the static
spin-stripe-ordering temperature T_{so} and the magnetic volume fraction V_{m}
were observed in La_{2-x}Ba_{x}CuO_{4}(x=1/8) by means of muon-spin-rotation
experiments. The corresponding OIE exponents were found to be alpha_{T_{so}}=
0.57(6) and alpha_{V_{m}}=-0.71(9), which are sign reversed to
alpha_{T_{c}}=0.46(6) measured for the superconducting transition temperature
T_{c}. This indicates that the electron-lattice interaction is involved in the
stripe formation and plays an important role in the competition between bulk
superconductivity and static stripe order in the cuprates.
PMID- 25126930
TI - Sharp low-energy feature in single-particle spectra due to forward scattering in
d-wave cuprate superconductors.
AB - There is an enormous interest in the renormalization of the quasiparticle (qp)
dispersion relation of cuprate superconductors both below and above the critical
temperature T_{c} because it enables the determination of the fluctuation
spectrum to which the qp's are coupled. A remarkable discovery by angle-resolved
photoemission spectroscopy (ARPES) is a sharp low-energy feature (LEF) in qp
spectra well below the superconducting energy gap but with its energy increasing
in proportion to T_{c} and its intensity increasing sharply below T_{c}. This
unexpected feature needs to be reconciled with d-wave superconductivity. Here, we
present a quantitative analysis of ARPES data from
Bi_{2}Sr_{2}CaCu_{2}O_{8+delta} (Bi2212) using Eliashberg equations to show that
the qp scattering rate due to the forward scattering impurities far from the Cu-O
planes is modified by the energy gap below T_{c} and shows up as the LEF. This is
also a necessary step to analyze ARPES data to reveal the spectrum of
fluctuations promoting superconductivity.
PMID- 25126932
TI - Scattering matrix formulation of the topological index of interacting fermions in
one-dimensional superconductors.
AB - We construct a scattering matrix formulation for the topological classification
of one-dimensional superconductors with effective time-reversal symmetry in the
presence of interactions. For an isolated system, Fidkowski and Kitaev have shown
that such systems have a Z_{8} topological classification. We here show that
these systems have a unitary scattering matrix at zero temperature when weakly
coupled to a normal-metal lead, with a topological index given by the trace of
the Andreev-reflection matrix, trr_{he}. With interactions, trr_{he} generically
takes on the finite set of values 0, +/-1, +/-2, +/-3, and +/-4. We show that the
two topologically equivalent phases with trr_{he}=+/-4 support emergent many-body
end states, which we identify to be a topologically protected Kondo-like
resonance. The path in phase space that connects these equivalent phases crosses
a non-Fermi-liquid fixed point where a multiple-channel Kondo effect develops.
Our results connect the topological index to transport properties, thereby
highlighting the experimental signatures of interacting topological phases in one
dimension.
PMID- 25126933
TI - Ultrafast quenching of the exchange interaction in a Mott insulator.
AB - We investigate how fast and how effective photocarrier excitation can modify the
exchange interaction J_{ex} in the prototype Mott-Hubbard insulator. We
demonstrate an ultrafast quenching of J_{ex} both by evaluating exchange
integrals from a time-dependent response formalism and by explicitly simulating
laser-induced spin precession in an antiferromagnet that is canted by an external
magnetic field. In both cases, the electron dynamics is obtained from
nonequilibrium dynamical mean-field theory. We find that the modified J_{ex}
emerges already within a few electron hopping times after the pulse, with a
reduction that is comparable to the effect of chemical doping.
PMID- 25126934
TI - Stochastic resonance in collective exciton-polariton excitations inside a GaAs
microcavity.
AB - We report the first observation of stochastic resonance in confined exciton
polaritons. We evidence this phenomena by tracking the polaritons behavior
through two stochastic resonance quantifiers namely the spectral magnification
factor and the signal-to-noise ratio. The evolution of the stochastic resonance
in the function of the modulation amplitude of the periodic excitation signal is
studied. Our experimental observations are well reproduced by numerical
simulations performed in the framework of the Gross-Pitaevskii equation under
stochastic perturbation.
PMID- 25126935
TI - Unifying the low-temperature photoluminescence spectra of carbon nanotubes: the
role of acoustic phonon confinement.
AB - At low temperature the photoluminescence of single-wall carbon nanotubes show a
large variety of spectral profiles ranging from ultranarrow lines in suspended
nanotubes to broad and asymmetrical line shapes that puzzle the current
interpretation in terms of exciton-phonon coupling. Here, we present a complete
set of photoluminescence profiles in matrix embedded nanotubes including
unprecedented narrow emission lines. We demonstrate that the diversity of the low
temperature luminescence profiles in nanotubes originates in tiny modifications
of their low-energy acoustic phonon modes. When low-energy modes are locally
suppressed, a sharp photoluminescence line as narrow as 0.7 meV is restored.
Furthermore, multipeak luminescence profiles with specific temperature dependence
show the presence of confined phonon modes.
PMID- 25126936
TI - Spin pumping and spin-transfer torques in antiferromagnets.
AB - Spin pumping and spin-transfer torques are two reciprocal phenomena widely
studied in ferromagnetic materials. However, pumping from antiferromagnets and
its relation to current-induced torques have not been explored. By calculating
how electrons scatter off a normal metal-antiferromagnetic interface, we derive
pumped spin and staggered spin currents in terms of the staggered field, the
magnetization, and their rates of change. For both compensated and uncompensated
interfaces, spin pumping is of a similar magnitude as in ferromagnets with a
direction controlled by the polarization of the driving microwave. The pumped
currents are connected to current-induced torques via Onsager reciprocity
relations.
PMID- 25126937
TI - Ultrafast exciton formation at the ZnO(1010) surface.
AB - We study the ultrafast quasiparticle dynamics in and below the ZnO conduction
band using femtosecond time-resolved two-photon photoelectron spectroscopy. Above
band gap excitation causes hot electron relaxation by electron-phonon scattering
down to the Fermi level E_{F} followed by ultrafast (200 fs) formation of a
surface exciton (SX). Transient screening of the Coulomb interaction reduces the
SX formation probability at high excitation densities near the Mott limit.
Located just below the surface, the SX are stable with regard to hydrogen-induced
work function modifications and thus the ideal prerequisite for resonant energy
transfer applications.
PMID- 25126938
TI - Incoherent control of the retinal isomerization in rhodopsin.
AB - We propose to control the retinal photoisomerization yield through the backaction
dynamics imparted by a nonselective optical measurement of the molecular
electronic state. This incoherent effect is easier to implement than comparable
coherent pulse shaping techniques, and is also robust to environmental noise. A
numerical simulation of the quantum dynamics shows that the isomerization yield
of this important biomolecule can be substantially increased above the natural
limit.
PMID- 25126911
TI - Beam-energy dependence of charge separation along the magnetic field in Au+Au
collisions at RHIC.
AB - Local parity-odd domains are theorized to form inside a quark-gluon plasma which
has been produced in high-energy heavy-ion collisions. The local parity-odd
domains manifest themselves as charge separation along the magnetic field axis
via the chiral magnetic effect. The experimental observation of charge separation
has previously been reported for heavy-ion collisions at the top RHIC energies.
In this Letter, we present the results of the beam-energy dependence of the
charge correlations in Au+Au collisions at midrapidity for center-of-mass
energies of 7.7, 11.5, 19.6, 27, 39, and 62.4 GeV from the STAR experiment. After
background subtraction, the signal gradually reduces with decreased beam energy
and tends to vanish by 7.7 GeV. This implies the dominance of hadronic
interactions over partonic ones at lower collision energies.
PMID- 25126939
TI - Effects of cattle management on oak regeneration in northern Californian
Mediterranean oak woodlands.
AB - Oak woodlands of Mediterranean ecosystems, a major component of biodiversity
hotspots in Europe and North America, have undergone significant land-use change
in recent centuries, including an increase in grazing intensity due to the
widespread presence of cattle. Simultaneously, a decrease in oak regeneration has
been observed, suggesting a link between cattle grazing intensity and limited oak
regeneration. In this study we examined the effect of cattle grazing on coast
live oak (Quercus agrifolia Nee) regeneration in San Francisco Bay Area,
California. We studied seedling, sapling and adult density of coast live oak as
well as vertebrate herbivory at 8 independent sites under two grazing conditions:
with cattle and wildlife presence (n = 4) and only with wildlife (n = 4). The
specific questions we addressed are: i) to what extent cattle management
practices affect oak density, and ii) what is the effect of rangeland management
on herbivory and size of young oak plants. In areas with cattle present, we found
a 50% reduction in young oak density, and plant size was smaller, suggesting that
survival and growth young plants in those areas are significantly limited. In
addition, the presence of cattle raised the probability and intensity of
herbivory (a 1.5 and 1.8-fold difference, respectively). These results strongly
suggest that the presence of cattle significantly reduced the success of young Q.
agrifolia through elevated herbivory. Given the potential impact of reduced
recruitment on adult populations, modifying rangeland management practices to
reduce cattle grazing pressure seems to be an important intervention to maintain
Mediterranean oak woodlands.
PMID- 25126941
TI - Growth factor stimulation improves the structure and properties of scaffold-free
engineered auricular cartilage constructs.
AB - The reconstruction of the external ear to correct congenital deformities or
repair following trauma remains a significant challenge in reconstructive
surgery. Previously, we have developed a novel approach to create scaffold-free,
tissue engineering elastic cartilage constructs directly from a small population
of donor cells. Although the developed constructs appeared to adopt the
structural appearance of native auricular cartilage, the constructs displayed
limited expression and poor localization of elastin. In the present study, the
effect of growth factor supplementation (insulin, IGF-1, or TGF-beta1) was
investigated to stimulate elastogenesis as well as to improve overall tissue
formation. Using rabbit auricular chondrocytes, bioreactor-cultivated constructs
supplemented with either insulin or IGF-1 displayed increased deposition of
cartilaginous ECM, improved mechanical properties, and thicknesses comparable to
native auricular cartilage after 4 weeks of growth. Similarly, growth factor
supplementation resulted in increased expression and improved localization of
elastin, primarily restricted within the cartilaginous region of the tissue
construct. Additional studies were conducted to determine whether scaffold-free
engineered auricular cartilage constructs could be developed in the 3D shape of
the external ear. Isolated auricular chondrocytes were grown in rapid-prototyped
tissue culture molds with additional insulin or IGF-1 supplementation during
bioreactor cultivation. Using this approach, the developed tissue constructs were
flexible and had a 3D shape in very good agreement to the culture mold (average
error <400 um). While scaffold-free, engineered auricular cartilage constructs
can be created with both the appropriate tissue structure and 3D shape of the
external ear, future studies will be aimed assessing potential changes in
construct shape and properties after subcutaneous implantation.
PMID- 25126940
TI - Selection signatures in worldwide sheep populations.
AB - The diversity of populations in domestic species offers great opportunities to
study genome response to selection. The recently published Sheep HapMap dataset
is a great example of characterization of the world wide genetic diversity in
sheep. In this study, we re-analyzed the Sheep HapMap dataset to identify
selection signatures in worldwide sheep populations. Compared to previous
analyses, we made use of statistical methods that (i) take account of the
hierarchical structure of sheep populations, (ii) make use of linkage
disequilibrium information and (iii) focus specifically on either recent or older
selection signatures. We show that this allows pinpointing several new selection
signatures in the sheep genome and distinguishing those related to modern
breeding objectives and to earlier post-domestication constraints. The newly
identified regions, together with the ones previously identified, reveal the
extensive genome response to selection on morphology, color and adaptation to new
environments.
PMID- 25126942
TI - Thermodynamics of the interaction between Alzheimer's disease related tau protein
and DNA.
AB - Tau hyperphosphorylation can be considered as one of the hallmarks of Alzheimer's
disease and other tauophaties. Besides its well-known role as a microtubule
associated protein, Tau displays a key function as a protector of genomic
integrity in stress situations. Phosphorylation has been proven to regulate
multiple processes including nuclear translocation of Tau. In this contribution,
we are addressing the physicochemical nature of DNA-Tau interaction including the
plausible influence of phosphorylation. By means of surface plasmon resonance
(SPR) we measured the equilibrium constant and the free energy, enthalpy and
entropy changes associated to the Tau-DNA complex formation. Our results show
that unphosphorylated Tau binding to DNA is reversible. This fact is in agreement
with the protective role attributed to nuclear Tau, which stops binding to DNA
once the insult is over. According to our thermodynamic data, oscillations in the
concentration of dephosphorylated Tau available to DNA must be the variable
determining the extent of Tau binding and DNA protection. In addition,
thermodynamics of the interaction suggest that hydrophobicity must represent an
important contribution to the stability of the Tau-DNA complex. SPR results
together with those from Tau expression in HEK cells show that phosphorylation
induces changes in Tau protein which prevent it from binding to DNA. The
phosphorylation-dependent regulation of DNA binding is analogous to the Tau
microtubules binding inhibition induced by phosphorylation. Our results suggest
that hydrophobicity may control Tau location and DNA interaction and that
impairment of this Tau-DNA interaction, due to Tau hyperphosphorylation, could
contribute to Alzheimer's pathogenesis.
PMID- 25126943
TI - Toll-like receptor 9-activation during onset of myocardial ischemia does not
influence infarct extension.
AB - AIM: Myocardial infarction (MI) remains a major cause of death and disability
worldwide, despite available reperfusion therapies. Inflammatory signaling is
considered nodal in defining final infarct size. Activation of the innate immune
receptor toll-like receptors (TLR) 9 prior to ischemia and reperfusion (I/R)
reduces infarct size, but the consequence of TLR9 activation timed to the onset
of ischemia is not known. METHODS AND RESULTS: The TLR9-agonist; CpG B was
injected i.p. in C57BL/6 mice immediately after induction of ischemia (30
minutes). Final infarct size, as well as area-at-risk, was measured after 24
hours of reperfusion. CpG B injection resulted in a significant increase in
circulating granulocytes and monocytes both in sham and I/R mice. Paradoxically,
clear evidence of reduced cardiac infiltration of both monocytes and granulocytes
could be demonstrated in I/R mice treated with CpG B (immunocytochemistry,
myeloperoxidase activity and mRNA expression patterns). In addition, systemic
TLR9 activation elicited significant alterations of cardiac inflammatory genes.
Despite these biochemical and cellular changes, there was no difference in
infarct size between vehicle and CpG B treated I/R mice. CONCLUSION: Systemic
TLR9-stimulation upon onset of ischemia and subsequent reperfusion does not alter
final infarct size despite causing clear alterations of both systemic and cardiac
inflammatory parameters. Our results question the clinical usefulness of TLR9
activation during cardiac I/R.
PMID- 25126945
TI - Treatment of FANCA cells with resveratrol and N-acetylcysteine: a comparative
study.
AB - Fanconi anemia (FA) is a genetic disorder characterised by chromosome
instability, cytokine ipersensibility, bone marrow failure and abnormal
haematopoiesis associated with acute myelogenous leukemia. Recent reports are
contributing to characterize the peculiar FA metabolism. Central to these
considerations appears that cells from complementation group A (FANCA) display an
altered red-ox metabolism. Consequently the possibility to improve FA
phenotypical conditions with antioxidants is considered. We have characterized
from the structural and biochemical point of view the response of FANCA
lymphocytes to N-acetyl-cysteine (NAC) and resveratrol (RV). Surprisingly both
NAC and RV failed to revert all the characteristic of FA phenotype and moreover
their effects are not super imposable. Our data suggest that we must be aware of
the biological effects coming from antioxidant treatment.
PMID- 25126946
TI - Development and validation of a prediction score for complications after
hepatectomy in hepatitis B-related hepatocellular carcinoma patients.
AB - OBJECTIVE AND BACKGROUND: The aim of the present study was to develop and
validate a prediction score for postoperative complications by severity and guide
perioperative management and patient selection in hepatitis B-related
hepatocellular carcinoma patients undergoing liver resection. METHODS: A total of
1543 consecutive liver resections cases were included in the study. Randomly
selected sample set of 70% of the study cohort was used to develop a score to
predict complications III-V and the remaining 30% was used to validate the score.
Based on the preoperative and predictable intraoperative parameters, logistic
regression analysis was used to identify risk factors and create an integer score
for the predicting of complication. RESULTS: American Society of
Anesthesiologists category, portal hypertension, major liver resection (more than
3 segments) and extrahepatic procedures were identified as independent predictors
for complications III-V by logistic regression analysis. A score system
integrating these 4 factors was stratified into three groups and significantly
predicted the risk of complications III-V, with a rate of 1.6%, 11.9% and 65.6%
for low, moderate and high risk, respectively. Using the score, the complications
risk could be predicted accurately in the validation set, without significant
differences between predicted (10.4%) and observed (8.4%) risks for complications
III-V (P = 0.466). CONCLUSIONS: Based on four preoperative risk factors, we have
developed and validated an integer-based risk score to predict postoperative
severe complications after liver resection for hepatitis B-related hepatocellular
carcinoma patients in high-volume surgical center. This score may contribute to
preoperative risk stratification and clinical decision-making.
PMID- 25126948
TI - Association of DNA methyltransferases 3A and 3B polymorphisms, and plasma folate
levels with the risk of urothelial carcinoma.
AB - BACKGROUND: Interindividual genetic variations of human DNA methyltransferases
(DNMTs), which involve the methyl donor from the folate-related one-carbon
metabolism pathway, are hypothesized as a risk factor for urothelial carcinoma
(UC). Therefore, we evaluated the role of gene-environment interaction in UC
carcinogenesis. METHODS: A hospital-based case-control study was conducted by
recruiting 192 patients with UC and 381 controls. Their plasma folate levels were
measured using a competitive immunoassay kit. In addition, DNMT3A -448A>G and
DNMT3B -579G>T genotyping was evaluated using a polymerase chain reaction
restriction fragment length polymorphism technique. Multivariate logistic
regression and 95% confidence intervals (CIs) were applied to estimate the UC
risk. RESULTS: We observed that patients with UC exhibited a higher prevalence
rate of folate insufficiency (folate levels <=6 ng/mL) compared with the controls
(35.94% and 18.37%, respectively). Furthermore, folate levels were higher in the
prevalent UC patients than in the incident UC patients. However, folate
insufficiency was similarly associated with a nearly two-fold increase in the
risk of UC regardless of the UC patient group. In addition, the frequencies of
the variant alleles for DNMT3A and DNMT3B were 0.80 and 0.92, respectively, and
no association was observed with UC risk. However, participants with a variant
homozygous genotype of DNMT3B -579G>T and folate insufficiency or with high
cumulative cigarette smoking exhibited an increased risk of UC. CONCLUSION:
Overall, environmental factors may contribute more significantly to UC
carcinogenesis compared with genetic susceptibility. Future studies should
investigate other polymorphisms of DNMT3A and DNMT3B to determine genetic
susceptibility.
PMID- 25126947
TI - Brain networks during free viewing of complex erotic movie: new insights on
psychogenic erectile dysfunction.
AB - Psychogenic erectile dysfunction (ED) is defined as a male sexual dysfunction
characterized by a persistent or recurrent inability to attain adequate penile
erection due predominantly or exclusively to psychological or interpersonal
factors. Previous fMRI studies were based on the common occurrence in the male
sexual behaviour represented by the sexual arousal and penile erection related to
viewing of erotic movies. However, there is no experimental evidence of altered
brain networks in psychogenic ED patients (EDp). Some studies showed that fMRI
activity collected during non sexual movie viewing can be analyzed in a reliable
manner with independent component analysis (ICA) and that the resulting brain
networks are consistent with previous resting state neuroimaging studies. In the
present study, we investigated the modification of the brain networks in EDp
compared to healthy controls (HC), using whole-brain fMRI during free viewing of
an erotic video clip. Sixteen EDp and nineteen HC were recruited after RigiScan
evaluation, psychiatric, and general medical evaluations. The performed ICA
showed that visual network (VN), default-mode network (DMN), fronto-parietal
network (FPN) and salience network (SN) were spatially consistent across EDp and
HC. However, between-group differences in functional connectivity were observed
in the DMN and in the SN. In the DMN, EDp showed decreased connectivity values in
the inferior parietal lobes, posterior cingulate cortex and medial prefrontal
cortex, whereas in the SN decreased and increased connectivity was observed in
the right insula and in the anterior cingulate cortex respectively. The decreased
levels of intrinsic functional connectivity principally involved the subsystem of
DMN relevant for the self relevant mental simulation that concerns remembering of
past experiences, thinking to the future and conceiving the viewpoint of the
other's actions. Moreover, the between group differences in the SN nodes
suggested a decreased recognition of autonomical and sexual arousal changes in
EDp.
PMID- 25126949
TI - Symptomatic and incidental venous thromboembolic disease are both associated with
mortality in patients with prostate cancer.
AB - INTRODUCTION: The association between malignancy and venous thromboembolic
disease (VTE) is well established. The independent impact of VTE, both
symptomatic and incidental, on survival in patients with prostate cancer is not
known. We conducted a retrospective cohort study to evaluate the effect of VTE of
survival in prostate cancer. METHODS: Data regarding clinical characteristics,
treatment and outcomes of 453 consecutive prostate cancer patients were
collected. Fisher exact (categorical variables) and t-test (continuous variables)
were utilized to test associations with VTE and mortality. Survival was estimated
using the Kaplan Meier method. A Cox regression model was used to model the
mortality hazard ratio (HR). RESULTS: At diagnosis, 358 (83%) patients had early
stage disease, 43 (10%) had locally advanced disease and 32 (7%) had metastatic
disease. During the follow up period, 122 (27%) patients died and 41 (9%)
developed VTE (33 deep vein thrombosis, 5 pulmonary embolism, and 3 patients with
both DVT and PE). Twenty-five VTE events were symptomatic and 16 were
incidentally diagnosed on CT scans obtained for other reasons. VTE was associated
with increased mortality [HR 6.89 (4.29-11.08), p<0.001] in a multivariable
analysis adjusted for cancer stage, performance status, treatments and co
morbidities. There was no difference in survival between patients who had
symptomatic and incidental VTE. CONCLUSION: Venous thromboembolic disease, both
symptomatic and incidental, is a predictor of poor survival in patients with
prostate cancer, especially those with advanced disease. Further studies are
needed to evaluate the benefit of prophylactic and therapeutic anticoagulation in
this population.
PMID- 25126950
TI - Aspirin delimits platelet life span by proteasomal inhibition.
AB - Aspirin is widely used in clinical settings as an anti-inflammatory and anti
platelet drug due its inhibitory effect on cyclooxygenase activity. Although the
drug has long been considered to be an effective and safe therapeutic regime
against inflammatory and cardiovascular disorders, consequences of its
cyclooxygenase-independent attributes on platelets, the key players in
thrombogenesis, beg serious investigation. In this report we explored the effect
of aspirin on platelet lifespan in murine model and its possible cytotoxicity
against human platelets in vitro. Aspirin administration in mice led to
significant reduction in half-life of circulating platelets, indicative of
enhanced rate of platelet clearance. Aspirin-treated human platelets were found
to be phagocytosed more efficiently by macrophages, associated with attenuation
in platelet proteasomal activity and upregulation of conformationally active Bax,
which were consistent with enhanced platelet apoptosis. Although the dosage of
aspirin administered in mice was higher than the therapeutic regimen against
cardiovascular events, it is comparable with the recommended anti-inflammatory
prescription. Thus, above observations provide cautionary framework to critically
re-evaluate prophylactic and therapeutic dosage regime of aspirin in systemic
inflammatory as well as cardiovascular ailments.
PMID- 25126951
TI - Positive feedback promotes oscillations in negative feedback loops.
AB - A simple three-component negative feedback loop is a recurring motif in
biochemical oscillators. This motif oscillates as it has the three necessary
ingredients for oscillations: a three-step delay, negative feedback, and
nonlinearity in the loop. However, to oscillate, this motif under the common
Goodwin formulation requires a high degree of cooperativity (a measure of
nonlinearity) in the feedback that is biologically "unlikely." Moreover, this
recurring negative feedback motif is commonly observed augmented by positive
feedback interactions. Here we show that these positive feedback interactions
promote oscillation at lower degrees of cooperativity, and we can thus unify
several common kinetic mechanisms that facilitate oscillations, such as self
activation and Michaelis-Menten degradation. The positive feedback loops are most
beneficial when acting on the shortest lived component, where they function by
balancing the lifetimes of the different components. The benefits of multiple
positive feedback interactions are cumulative for a majority of situations
considered, when benefits are measured by the reduction in the cooperativity
required to oscillate. These positive feedback motifs also allow oscillations
with longer periods than that determined by the lifetimes of the components
alone. We can therefore conjecture that these positive feedback loops have
evolved to facilitate oscillations at lower, kinetically achievable, degrees of
cooperativity. Finally, we discuss the implications of our conclusions on the
mammalian molecular clock, a system modeled extensively based on the three
component negative feedback loop.
PMID- 25126952
TI - Combined photothermal and photodynamic therapy delivered by PEGylated MoS2
nanosheets.
AB - Single- or few-layered transitional metal dichalcogenides, as a new genus of two
dimensional nanomaterials, have attracted tremendous attention in recent years,
owing to their various intriguing properties. In this study, chemically
exfoliated MoS2 nanosheets are modified with lipoic acid-terminated polyethylene
glycol (LA-PEG), obtaining PEGylated MoS2 (MoS2-PEG) with high stability in
physiological solutions and no obvious toxicity. Taking advantage of its ultra
high surface area, the obtained MoS2-PEG is able to load a photodynamic agent,
chlorin e6 (Ce6), by physical adsorption. In vitro experiments reveal that Ce6
after being loaded on MoS2-PEG shows remarkably increased cellular uptake and
thus significantly enhanced photodynamic therapeutic efficiency. Utilizing the
strong, near-infrared (NIR) absorbance of the MoS2 nanosheets, we further
demonstrate photothermally enhanced photodynamic therapy using Ce6-loaded MoS2
PEG for synergistic cancer killing, in both in vitro cellular and in vivo animal
experiments. Our study presents a new type of multifunctional nanocarrier for the
delivery of photodynamic therapy, which, if combined with photothermal therapy,
appears to be an effective therapeutic approach for cancer treatment.
PMID- 25126953
TI - Differential activity of Striga hermonthica seed germination stimulants and
Gigaspora rosea hyphal branching factors in rice and their contribution to
underground communication.
AB - Strigolactones (SLs) trigger germination of parasitic plant seeds and hyphal
branching of symbiotic arbuscular mycorrhizal (AM) fungi. There is extensive
structural variation in SLs and plants usually produce blends of different SLs.
The structural variation among natural SLs has been shown to impact their
biological activity as hyphal branching and parasitic plant seed germination
stimulants. In this study, rice root exudates were fractioned by HPLC. The
resulting fractions were analyzed by MRM-LC-MS to investigate the presence of SLs
and tested using bioassays to assess their Striga hermonthica seed germination
and Gigaspora rosea hyphal branching stimulatory activities. A substantial number
of active fractions were revealed often with very different effect on seed
germination and hyphal branching. Fractions containing (-)-orobanchol and ent-2'
epi-5-deoxystrigol contributed little to the induction of S. hermonthica seed
germination but strongly stimulated AM fungal hyphal branching. Three SLs in one
fraction, putative methoxy-5-deoxystrigol isomers, had moderate seed germination
and hyphal branching inducing activity. Two fractions contained strong
germination stimulants but displayed only modest hyphal branching activity. We
provide evidence that these stimulants are likely SLs although no SL
representative masses could be detected using MRM-LC-MS. Our results show that
seed germination and hyphal branching are induced to very different extents by
the various SLs (or other stimulants) present in rice root exudates. We propose
that the development of rice varieties with different SL composition is a
promising strategy to reduce parasitic plant infestation while maintaining
symbiosis with AM fungi.
PMID- 25126954
TI - Gynecologic Cancer InterGroup (GCIG) consensus review for squamous cell carcinoma
of the ovary.
AB - Squamous cell carcinoma of the ovary is a rare complication of mature cystic
teratoma. The epidemiology, pathology, diagnosis, and management of this rare
tumor are reviewed. Clinical characteristics, preoperative imaging, and tumor
markers may help to predict malignancy preoperatively. Complete cytoreduction
should be the aim of surgery. The prognosis for stage 1A disease is good, but for
women with advanced or recurrent disease, it is very poor and has not improved in
recent years. At present, there are insufficient data to provide clear guidance
on the optimal management strategy for advanced disease, and there is a need to
gain an understanding of the biology and to develop novel effective therapies.
This will require coordinated international collaboration.
PMID- 25126955
TI - Is removing 9 lymph nodes a correct cutoff to define optimal lymphadenectomy?:
The open question of lymph node count.
PMID- 25126956
TI - The clinical perspectives of CDX2 expression in colorectal cancer: a qualitative
systematic review.
AB - INTRODUCTION: Homeobox genes are often deregulated in cancer. They can have both
oncogenic and tumor-suppressing potential. The Caudal-related homeobox
transcription factor 2 (CDX2) is an intestine-specific transcription factor. It
is implicated in differentiation, proliferation, cell-adhesion, and migration.
CDX2 has been proposed as a tumor suppressor in colorectal cancer but its role is
still controversial. This systematic review were undertaken in order to clarify
CDX2s role in colorectal cancer. METHODS: A literature search was performed in
the MEDLINE database from 1966 to February 2014. Only studies in which all or a
part of the experimental design were performed on human colorectal cancer tissue
were included. Thus, studies solely performed in cell-lines or animal models were
excluded. RESULTS: Fifty-two articles of relevance were identified. CDX2
expression was rarely lost in colorectal cancers, however the expression pattern
may often be heterogeneous within the tumor and can be selectively down regulated
at the invasive front and in tumor buddings. Loss of CDX2 expression is probably
correlated to tumor grade, stage, right-sided tumor location, MMR-deficiency,
CIMP, and BRAF mutations. The CDX2 gene is rarely mutated but the locus harboring
the gene is often amplified and may suggest CDX2 as a linage-survival oncogene.
CDX2 might be implicated in cell proliferation and migration through cross-talk
with the Wnt-signaling pathway, tumor-stroma proteins, and inflammatory
cytokines. CONCLUSION: A clear role for CDX2 expression in colorectal cancer
remains to be elucidated, and it might differ in relation to the underlying
molecular pathways leading to the cancer formation.
PMID- 25126957
TI - A double-blind, placebo-controlled trial related to the effects of melatonin on
oxidative stress and inflammatory parameters of obese women.
AB - Obesity, the global epidemic health problem, results in chronic disorders.
Melatonin supplementation may prevent the adverse health consequences of obesity.
The aim of this study was to assess the effects of melatonin supplementation on
inflammatory and oxidative stress parameters in obese women. In randomized,
double-blind, placebo-controlled trial, 44 obese women were randomly assigned to
melatonin (n=22) and placebo (n=22) groups. Subjects were supplemented with a
daily dose of 6 mg melatonin or placebo with low calorie diet for 40 days. Serum
TNF-alpha, IL-6, hsCRP, TAC, and MDA levels were assessed before and after
intervention. In the melatonin group, mean serum TNF-alpha, IL-6, hsCRP, and MDA
levels decreased significantly (p<0.05) from 3.52+/-0.72 pg/ml, 27.12+/-6.32
pg/ml, 2.54+/-0.49 mg/l, and 3.81+/-0.29 nmol/l to 1.73+/-0.07, 16.34+/-6.32,
1.67+/-0.27, and 2.79+/-0.29, respectively. Whilst in the placebo group the
decrease in values were not statistically significant. Mean TAC level increased
slightly (from 1.11+/-0.30 to 1.14+/-0.45 mmol/l) in the melatonin group whereas
it decreased slightly (from 1.13+/-0.15 to 1.08+/-0.21 nmol/l) in the placebo
group. Significant differences were observed only for TNF-alpha (p=0.02) and IL-6
(p=0.03) between the 2 study groups. Considering the improvements in inflammatory
and oxidative stress factors in obese women, it seems that melatonin
supplementation may provide beneficial effects in obesity treatment by
ameliorating some of its complications. However, further studies are needed to
make concise conclusions.
PMID- 25126958
TI - Crystal structure of the homology domain of the eukaryotic DNA replication
proteins Sld3/Treslin.
AB - The initiation of eukaryotic chromosomal DNA replication requires the formation
of an active replicative helicase at the replication origins of chromosomal DNA.
Yeast Sld3 and its metazoan counterpart Treslin are the hub proteins mediating
protein associations critical for the helicase formation. Here, we show the
crystal structure of the central domain of Sld3 that is conserved in Sld3/Treslin
family of proteins. The domain consists of two segments with 12 helices and is
sufficient to bind to Cdc45, the essential helicase component. The structure
model of the Sld3-Cdc45 complex, which is crucial for the formation of the active
helicase, is proposed.
PMID- 25126959
TI - Structural basis for the SOX-dependent genomic redistribution of OCT4 in stem
cell differentiation.
AB - In pluripotent cells, OCT4 associates with SOX2 to maintain pluripotency or with
SOX17 to induce primitive endoderm commitment. The OCT4-SOX2 and OCT4-SOX17
combinations bind mutually exclusive to two distinct composite DNA elements,
known as the "canonical" and "compressed" motifs, respectively. The structural
basis for the OCT4-SOX17 cooperativity is unknown. Whereas SOX17 has been
engineered to replace SOX2 in the pluripotency circuitry, all generated SOX2
mutants have failed to act like SOX17. From molecular simulations, we revealed
the OCT4-SOX17 interaction interface and elucidated the SOX-dependent motif
preference of OCT4. Moreover, we designed a SOX2 mutant that we predicted and
confirmed experimentally to bind cooperatively with OCT4 to the compressed motif.
Ultimately, we found a strong correlation between the experimental and calculated
relative cooperative-binding free energies of 12 OCT4-SOX-DNA complexes.
Therefore, we validated the OCT4-SOX interfaces and demonstrated that in silico
design of DNA-binding cooperativity is suitable for altering transcriptional
circuitries.
PMID- 25126961
TI - Circuit topology of proteins and nucleic acids.
AB - Folded biomolecules display a bewildering structural complexity and diversity.
They have therefore been analyzed in terms of generic topological features. For
instance, folded proteins may be knotted, have beta-strands arranged into a Greek
key motif, or display high contact order. In this perspective, we present a
method to formally describe the topology of all folded linear chains and hence
provide a general classification and analysis framework for a range of
biomolecules. Moreover, by identifying the fundamental rules that intrachain
contacts must obey, the method establishes the topological constraints of folded
linear chains. We also briefly illustrate how this circuit topology notion can be
applied to study the equivalence of folded chains, the engineering of artificial
RNA structures and DNA origami, the topological structure of genomes, and the
role of topology in protein folding.
PMID- 25126962
TI - Comprehension asymmetries in language acquisition: a test for Relativized
Minimality.
AB - Cross-linguistic studies have shown that typically developing children have
difficulties comprehending non-canonical structures. These findings have been
interpreted within the Relativized Minimality (RM) approach, according to which
local relations cannot be established between two terms of a dependency if an
intervening element possesses similar morphosyntactic features. In an extension
of RM, Friedmann, Belletti, and Rizzi (2009) suggested that lexical NP
restriction is the source of minimality effects in non-canonical sentences. The
present study aimed at investigating whether the predictions of their account can
be confirmed in Greek. Our results indicate that although lexical NP restriction
is a crucial factor in generating minimality effects, it is not always sufficient
to account for the comprehension difficulties that young children face with non
canonical sentences, since the internal structure (i.e. the feature
specification) of the moved element and of the intervener affects their
performance, as well.
PMID- 25126960
TI - The structure of mouse cytomegalovirus m04 protein obtained from sparse NMR data
reveals a conserved fold of the m02-m06 viral immune modulator family.
AB - Immunoevasins are key proteins used by viruses to subvert host immune responses.
Determining their high-resolution structures is key to understanding virus-host
interactions toward the design of vaccines and other antiviral therapies. Mouse
cytomegalovirus encodes a unique set of immunoevasins, the m02-m06 family, that
modulates major histocompatibility complex class I (MHC-I) antigen presentation
to CD8+ T cells and natural killer cells. Notwithstanding the large number of
genetic and functional studies, the structural biology of immunoevasins remains
incompletely understood, largely because of crystallization bottlenecks. Here we
implement a technology using sparse nuclear magnetic resonance data and
integrative Rosetta modeling to determine the structure of the m04/gp34
immunoevasin extracellular domain. The structure reveals a beta fold that is
representative of the m02-m06 family of viral proteins, several of which are
known to bind MHC-I molecules and interfere with antigen presentation, suggesting
its role as a diversified immune regulation module.
PMID- 25126963
TI - Comprehensive approach to systemic sclerosis patients during pregnancy.
AB - Systemic sclerosis (SSc) is a connective tissue disease that usually affects
women, with a male:female ratio of 1:4-10. It was thought that there was a
prohibitive risk of fatal complications in the pregnancies of patients with SSc.
It is now known that the majority of these women undergo a normal progression of
pregnancy if the right time is chosen and a close obstetric care is delivered.
The obstetric risk will depend on the subtype and clinical stage of the disease,
and the presence and severity of the internal organ involvement during the
pregnancy. The management of these pregnancies should be provided in a
specialized center, with a multidisciplinary team capable of identifying and
promptly treating complications. Treatment should be limited to drugs with no
teratogenic potential, except when renal crises or severe cardiovascular
complications develop.
PMID- 25126965
TI - Evidence-based care for trilateral retinoblastoma.
PMID- 25126964
TI - Trilateral retinoblastoma: a systematic review and meta-analysis.
AB - BACKGROUND: About 5% of children with retinoblastoma from germline mutation of
the RB1 gene are at risk of developing trilateral retinoblastoma--intraocular
retinoblastoma combined with a histologically similar brain tumour, most commonly
in the pineal gland. We aimed to provide a systematic overview of published data
for trilateral retinoblastoma, and to analyse how survival has changed. METHODS:
We searched Medline and Embase for scientific literature published between Jan 1,
1966, and April 14, 2014, that assessed trilateral retinoblastoma cases. We
undertook a meta-analysis of survival with the Kaplan-Meier method and Cox
proportional hazards regression, stratified on the basis of the original study,
to account for between-study heterogeneity. FINDINGS: We included 90 studies,
with 174 patients with trilateral retinoblastoma. 5-year survival after pineal
trilateral retinoblastoma increased from 6% (95% CI 2-15) in patients diagnosed
before 1995, to 44% (26-61; p<0.0001) in those diagnosed from 1995 onwards.
Before 1995, no patients with non-pineal trilateral retinoblastoma survived, but
from 1995 onwards, 5-year survival was 57% (30-77; p=0.035). Hazard ratios (HR)
adjusted for the presence of leptomeningeal metastases and trilateral
retinoblastoma location, suggested that both conventional (HR 0.059, 95% CI 0.016
0.226; p<0.0001) and high-dose chemotherapy with stem-cell rescue (0.013, 0.002
0.064; p<0.0001) most strongly contributed to this improvement. Absence of
leptomeningeal metastases (HR 2.13, 95% CI 0.98-4.60; p=0.055) were associated
with improved survival. Non-pineal trilateral retinoblastomas were larger than
pineal tumours (median 30 mm [range 6-100] vs 22 mm [7-60]; p=0.012), but both
had similar outcomes since 1995. INTERPRETATION: Our results suggest that
improvements in overall survival are attributable to improved chemotherapy
regimens and early detection of pineal trilateral retinoblastoma. As such,
successful treatment of trilateral retinoblastoma should include screening at
least at the time of retinoblastoma diagnosis and chemotherapy, which would
preferably be a high-dose regimen with autologous stem-cell rescue. FUNDING:
None.
PMID- 25126966
TI - Solid-phase dispersive extraction method for analysis of benzodiazepine drugs in
serum and urine samples.
AB - A simple yet highly efficient pretreatment method called solid-phase dispersive
extraction (SPDE) was developed and used in combination with liquid
chromatography/time-of-flight mass spectrometry (LC/TOF-MS) for the analysis of
benzodiazepines (BZPs) in serum and urine samples. By using a custom-made
centrifugal filter, SPDE could be performed in a closed system, thereby
minimizing exposure to infectious microbes or hazardous chemicals. The limit of
detection and the limit of quantification of nine BZPs were 1-10 and 5-50ng/mL,
respectively. The average recoveries of BZPs from pooled serum samples spiked at
50 and 500ng/mL were 89.6-105.0% (RSD: 2.1-6.8%) and 93.6-110.4% (RSD: 2.1-4.2%),
respectively, and those from urine samples were 88.7-105.5% (RSD: 2.9-6.4%) and
91.5-101.1% (RSD: 3.6-5.5%), respectively. SPDE-LC/TOF-MS has potential
application in forensic science and emergency medicine.
PMID- 25126968
TI - Development of a selective agar plate for the detection of Campylobacter spp. in
fresh produce.
AB - This study was conducted to develop a selective medium for the detection of
Campylobacter spp. in fresh produce. Campylobacter spp. (n=4), non-Campylobacter
(showing positive results on Campylobacter selective agar) strains (n=49)
isolated from fresh produce, indicator bacteria (n=13), and spoilage bacteria
isolated from fresh produce (n=15) were plated on four Campylobacter selective
media. Bolton agar and modified charcoal cefoperazone deoxycholate agar (mCCDA)
exhibited higher sensitivity for Campylobacter spp. than did Preston agar and
Hunt agar, although certain non-Campylobacter strains isolated from fresh produce
by using a selective agar isolation method, were still able to grow on Bolton
agar and mCCDA. To inhibit the growth of non-Campylobacter strains, Bolton agar
and mCCDA were supplemented with 5 antibiotics (rifampicin, polymyxin B, sodium
metabisulfite, sodium pyruvate, ferrous sulfate) and the growth of Campylobacter
spp. (n=7) and non-Campylobacter strains (n=44) was evaluated. Although Bolton
agar supplemented with rifampicin (BR agar) exhibited a higher selectivity for
Campylobacter spp. than did mCCDA supplemented with antibiotics, certain non
Campylobacter strains were still able to grow on BR agar (18.8%). When BR agar
with various concentrations of sulfamethoxazole-trimethoprim were tested with
Campylobacter spp. (n=8) and non-Campylobacter (n=7), sulfamethoxazole
trimethoprim was inhibitory against 3 of 7 non-Campylobacter strains. Finally, we
validated the use of BR agar containing 50mg/L sulfamethoxazole (BRS agar) or
0.5mg/L ciprofloxacin (BRCS agar) and other selective agars for the detection of
Campylobacter spp. in chicken and fresh produce. All chicken samples were
positive for Campylobacter spp. when tested on mCCDA, BR agar, and BRS agar. In
fresh produce samples, BRS agar exhibited the highest selectivity for
Campylobacter spp., demonstrating its suitability for the detection of
Campylobacter spp. in fresh produce.
PMID- 25126969
TI - Exploring the role of parents and peers in young adolescents' risk taking on
social networking sites.
AB - This study investigated the role of parental and peer mediation in young
adolescents' engagement in risk-taking in social networking sites (SNSs). A
survey conducted in Malaysia with 469 SNS users aged 13-14 revealed that control
based parental mediation can cause boomerang effects, making young adolescents
more inclined to taking risks in SNSs. While discussion-based parental mediation
was found to be negatively related to young adolescents' befriending strangers in
SNSs, it did not reduce privacy risks. Findings also suggested that peer
influence could result in undesirable outcomes. In particular, the more young
adolescents talked about Internet-related issues with peers, the more likely they
were to disclose personally identifiable information on SNSs.
PMID- 25126970
TI - Response to the letter by Olivier Barbier, Didier Ollat, Gilbert Versier.
PMID- 25126967
TI - Nerve growth factor mediates a switch in intracellular signaling for PGE2-induced
sensitization of sensory neurons from protein kinase A to Epac.
AB - We examined whether nerve growth factor (NGF), an inflammatory mediator that
contributes to chronic hypersensitivity, alters the intracellular signaling that
mediates the sensitizing actions of PGE2 from activation of protein kinase A
(PKA) to exchange proteins directly activated by cAMP (Epacs). When isolated
sensory neurons are grown in the absence of added NGF, but not in cultures grown
with 30 ng/ml NGF, inhibiting protein kinase A (PKA) activity blocks the ability
of PGE2 to augment capsaicin-evoked release of the neuropeptide CGRP and to
increase the number of action potentials (APs) evoked by a ramp of current.
Growing sensory neurons in culture in the presence of increasing concentrations
of NGF increases the expression of Epac2, but not Epac1. An intradermal injection
of complete Freund's adjuvant into the rat hindpaw also increases the expression
of Epac2, but not Epac1 in the dorsal root ganglia and spinal cord: an effect
blocked by intraplantar administration of NGF antibodies. Treating cultures grown
in the presence of 30 ng/ml NGF with Epac1siRNA significantly reduced the
expression of Epac1, but not Epac2, and did not block the ability of PGE2 to
augment capsaicin-evoked release of CGRP from sensory neurons. Exposing neuronal
cultures grown in NGF to Epac2siRNAreduced the expression of Epac2, but not Epac1
and prevented the PGE2-induced augmentation of capsaicin and potassium-evoked
CGRP release in sensory neurons and the PGE2-induced increase in the number of
APs generated by a ramp of current. In neurons grown with no added NGF, Epac
siRNAs did not attenuate PGE2-induced sensitization. These results demonstrate
that NGF, through increasing Epac2 expression, alters the signaling cascade that
mediates PGE2-induced sensitization of sensory neurons, thus providing a novel
mechanism for maintaining PGE2-induced hypersensitivity during inflammation.
PMID- 25126971
TI - Adoption of the 16-month American Board of Radiology pathway to dual board
certifications in nuclear radiology and/or nuclear medicine for diagnostic
radiology residents.
AB - RATIONALE AND OBJECTIVES: In 2010, the American Board of Radiology (ABR) approved
a new 16-month nuclear subspecialty training pathway within a standard 48-month
Accreditation Council for Graduate Medical Education (ACGME)-accredited
diagnostic radiology (DR) residency available to institutions sponsoring ACGME
accredited nuclear radiology (NR) and/or nuclear medicine (NM) program(s). This
accelerated pathway leads to eligibility for dual ABR certifications in DR and NR
or in NM by the American Board of Nuclear Medicine (ABNM). The American College
of Radiology, in conjunction with the ABR, aimed to understand adoption of this
new pathway, barriers to implementation, preferences for subspecialty
certification, and competing alternative combined DR/NR/NM training pathways.
MATERIALS AND METHODS: During 2013-2014, there were 20 ACGME-accredited NR
fellowship and 43 ACGME-accredited NM residency programs eligible to adopt this
new 16-month pathway. They were surveyed by e-mail correspondence regarding
implementation and barriers to implementation, board certification (ABR-NR and
ABNM) preferences, and local alternative training pathways. RESULTS: With 100% of
the surveys completed, a small cadre of qualifying DR programs (14, 22%) has
adopted (9, 14%) or is seriously considering adopting (5, 8%) the 16-month ABR
pathway. For most, implementation is problematic with numerous barriers in
common. Five (8%) institutions are developing 60-month nontraditional models as
alternative routes to ABR-DR/ABR-NR certifications and/or dual ABR/ABNM board
certifications. CONCLUSIONS: In spite of strategies to promote a shortened
training pathway in NR/NM, traditional subspecialty fellowships outside the DR
residency remain the dominant pathway leading to ABR subspecialty certification
in NR and/or ABNM certification for diagnostic radiologists.
PMID- 25126972
TI - Intrapleural fluid infusion for MR-guided high-intensity focused ultrasound
ablation in the liver dome.
AB - RATIONALE AND OBJECTIVES: Magnetic resonance-guided high-intensity focused
ultrasound (MR-HIFU) ablation of tumors in the liver dome is challenging because
of the presence of air in the costophrenic angle. In this study, we used a
porcine liver model and a clinical MR-HIFU system to assess the feasibility and
safety of using intrapleural fluid infusion (IPI) to create an acoustic window
for MR-HIFU ablation in the liver dome. MATERIALS AND METHODS: Healthy adult
Dalland land pigs (n = 6) under general anesthesia were used with animal
committee approval. Degassed saline (200-800 mL) was infused into the
intrapleural space under ultrasound guidance. A clinical 1.5-T MR-HIFU system was
used to perform sonications (4-mm treatment cells, 300-450 W, 20-30 seconds) in
the liver dome under real-time MR thermometry. An intercostal firing technique
was used to prevent rib heating in one experiment. Technical success was defined
as a temperature increase (>10 degrees C) in the target area. After termination,
the animal was examined for thermal damage to liver, diaphragm, pleura, lung, or
intercostal muscle. RESULTS: An acoustic window was established in all animals. A
temperature increase in the target area was achieved in all animals (max. 47
degrees C-67 degrees C). MR thermometry showed no heating outside the target
area. Intercostal firing effectively reduced rib heating (55 degrees C vs. 42
degrees C). Postmortem examination revealed no unwanted thermal damage. One
complication occurred, in the first experiment, because of an ill-suited needle
(displacement of the needle). CONCLUSIONS: The results indicate that IPI may be
used safely to assist MR-HIFU ablation of tumors in the liver dome. For reliable
tissue coagulation, IPI must be combined with an intercostal sonication
technique. Considering the proportion of patients with tumors in the liver dome,
IPI widens the applicability of MR-HIFU ablation for liver tumors considerably.
PMID- 25126973
TI - Breast MRI BI-RADS assessments and abnormal interpretation rates by clinical
indication in US community practices.
AB - RATIONALE AND OBJECTIVES: As breast magnetic resonance imaging (MRI) use grows,
benchmark performance parameters are needed for auditing and quality assurance
purposes. We describe the variation in breast MRI abnormal interpretation rates
(AIRs) by clinical indication among a large sample of US community practices.
MATERIALS AND METHODS: We analyzed data from 41 facilities across five Breast
Cancer Surveillance Consortium imaging registries. Each registry obtained
institutional review board approval for this Health Insurance Portability and
Accountability Act compliant analysis. We included 11,654 breast MRI examinations
conducted in 2005-2010 among women aged 18-79 years. We categorized clinical
indications as 1) screening, 2) extent of disease, 3) diagnostic (eg, breast
symptoms), and 4) other (eg, short-interval follow-up). We characterized
assessments as positive (ie, Breast Imaging Reporting and Data System [BI-RADS]
0, 4, and 5) or negative (ie, BI-RADS 1, 2, and 6) and provide results with BI
RADS 3 categorized as positive and negative. We tested for differences in AIRs
across clinical indications both unadjusted and adjusted for patient
characteristics and registry and assessed for changes in AIRs by year within each
clinical indication. RESULTS: When categorizing BI-RADS 3 as positive, AIRs were
21.0% (95% confidence interval [CI], 19.8-22.3) for screening, 31.7% (95% CI,
29.6-33.8) for extent of disease, 29.7% (95% CI, 28.3-31.1) for diagnostic, and
27.4% (95% CI, 25.0-29.8) for other indications (P < .0001). When categorizing BI
RADS 3 as negative, AIRs were 10.5% (95% CI, 9.5-11.4) for screening, 21.8% (95%
CI, 19.9-23.6) for extent of disease, 17.7% (95% CI, 16.5-18.8) for diagnostic,
and 13.3% (95% CI, 11.6-15.2) for other indications (P < .0001). The significant
differences in AIRs by indication persisted even after adjusting for patient
characteristics and registry (P < .0001). In addition, for most indications,
there were no significant changes in AIRs over time. CONCLUSIONS: Breast MRI AIRs
differ significantly by clinical indication. Practices should stratify breast MRI
examinations by indication for quality assurance and auditing purposes.
PMID- 25126974
TI - Comparison between multivolume CT-based surrogates of regional ventilation in
healthy subjects.
AB - RATIONALE AND OBJECTIVES: The assessment of regional ventilation is of critical
importance when investigating lung function during disease progression and
planning of pulmonary interventions. Recently, different computed tomography (CT)
based parameters have been proposed as surrogates of lung ventilation. The aim of
the present study was to compare these parameters, namely variations of density
(DeltaHU), specific volume (sVol), and specific gas volume (DeltaSVg) between
different lung volumes, in relation to their topographic distribution within the
lung. MATERIALS AND METHODS: Ten healthy volunteers were scanned via high
resolution CT at residual volume (RV) and total lung capacity (TLC); DeltaHU,
sVol, and DeltaSVg were mapped voxel by voxel after registering TLC onto RV.
Variations of the three parameters along the vertical and horizontal directions
were analyzed. RESULTS: Along the vertical direction (from ventral to dorsal
regions), a strong dependence on gravity was found in DeltaHU and sVol, with
greater values in the dorsal regions of the lung (P < .001), whereas DeltaSVg was
more homogeneously distributed within the lung. Conversely, along the
caudocranial direction (from lung bases to apexes) where no gravitational
gradient is present, the three parameters behaved similarly, with lower values at
the apices. CONCLUSIONS: DeltaHU, sVol, and DeltaSVg behave differently along the
gravity direction. As the greater amount of air delivered to the dependent
portion of the lung supplies a larger number of alveoli, the amount of gas
delivered to alveoli compared to the mass of tissue is not gravity dependent. The
minimization of gravity dependence in the distribution of ventilation when using
DeltaSVg suggests that this parameter is more reliable to discriminate healthy
from pathologic regions.
PMID- 25126976
TI - Environmental sampling for Clostridium difficile on alcohol-based hand rub
dispensers in an academic medical center.
AB - BACKGROUND: Clostridum difficile is a gram-positive, spore-forming anaerobic
bacillus that has substantial associated morbidity, mortality, and associated
healthcare burdens. Clostridium difficile spores are not destroyed by alcohol.
Alcohol gel dispensers are used commonly as the hand sanitization method of
choice in hospitals. It is possible that gel dispensers are fomites for C.
difficile. METHODS: Thirty alcohol-based gel dispenser handles outside of rooms
of patients with active C. difficile infection were sampled. The samples were
assessed for C. difficile by both culture and polymerase chain reaction (PCR).
The samples were also assessed for other organisms by culture. RESULTS: No C.
difficile was cultured or detected by PCR on any of the gel dispensers. Coagulase
negative Staphyloccus spp., diptheroids, and Bacillus spp. were the organisms
detected most commonly. CONCLUSION: At our institution, C. difficile is not
present on alcohol-based gel dispensers, but other potentially pathogenis are.
PMID- 25126975
TI - A pharmacogenetics-based warfarin maintenance dosing algorithm from Northern
Chinese patients.
AB - Inconsistent associations with warfarin dose were observed in genetic variants
except VKORC1 haplotype and CYP2C9*3 in Chinese people, and few studies on
warfarin dose algorithm was performed in a large Chinese Han population lived in
Northern China. Of 787 consenting patients with heart-valve replacements who were
receiving long-term warfarin maintenance therapy, 20 related Single nucleotide
polymorphisms were genotyped. Only VKORC1 and CYP2C9 SNPs were observed to be
significantly associated with warfarin dose. In the derivation cohort (n = 551),
warfarin dose variability was influenced, in decreasing order, by VKORC1 rs7294
(27.3%), CYP2C9*3(7.0%), body surface area(4.2%), age(2.7%), target INR(1.4%),
CYP4F2 rs2108622 (0.7%), amiodarone use(0.6%), diabetes mellitus(0.6%), and
digoxin use(0.5%), which account for 45.1% of the warfarin dose variability. In
the validation cohort (n = 236), the actual maintenance dose was significantly
correlated with predicted dose (r = 0.609, P<0.001). Our algorithm could improve
the personalized management of warfarin use in Northern Chinese patients.
PMID- 25126977
TI - Preventing intraperitoneal adhesions with ethyl pyruvate and hyaluronic
acid/carboxymethylcellulose: a comparative study in an experimental model.
AB - OBJECTIVE: To compare the effectiveness of ethyl pyruvate (EP) with that of
hyaluronic acid+carboxymethyl cellulose (Seprafilm) for the prevention of
intraperitoneal adhesions. Seprafilm has been shown to be effective in many
experimental and clinical studies. STUDY DESIGN: Thirty rats were divided into
three groups at random, and uterine horn abrasion was performed by laparotomy.
One group received no treatment (control group), one group received a single
intraperitoneal dose of EP 50mg/kg (EP group), and a 2*1-cm patch of Seprafilm
was applied in the third group (Seprafilm group). All rats were killed 14 days
after surgery. Macroscopic and histopathological evaluation were performed by a
surgeon and a pathologist who were blinded to group allocation.
Histopathologically, inflammation, fibroblastic activity, foreign body reaction,
collagen proliferation, vascular proliferation, Masson-Trichrome score, matrix
metalloproteinase-2 score and vascular endothelial growth factor score were
studied. RESULTS: Median macroscopic intraperitoneal adhesion scores for the
control, EP and Seprafilm groups were 2.8, 1.2 and 1.1, respectively. Multiple
comparisons between groups showed a significant difference (p<0.05). In binary
comparisons, significant differences were found between the control group and the
EP group, and between the control group and the Seprafilm group (p<0.05). No
significant difference was found between the adhesion scores for the EP group and
the Seprafilm group (p>0.05). After histopathological evaluation, significant
differences in all parameters were found between the groups (p<0.05). In the
paired comparison, significant differences were found between the control group
and the EP group, and between the control group and the Seprafilm group
(p<0.0167), but no significant difference was found between the EP group and the
Seprafilm group (p>0.0167). CONCLUSIONS: In comparison with the untreated control
group, EP and Seprafilm were found to reduce the formation of intraperitoneal
adhesions. No significant difference was found between EP and Seprafilm.
PMID- 25126978
TI - A perineal protection device designed to protect the perineum during labor: a
multicenter randomized controlled trial.
AB - OBJECTIVE: The objective of this study was to evaluate the protective effects of
a new device for reducing perineal tears during vaginal childbirth. STUDY DESIGN:
A multicenter open randomized controlled trial (RCT) was performed in
Helsingborg, Lund and Malmo, Sweden consisting of 1148 women. Women anticipating
a vaginal delivery were either randomized to the intervention group (n=574 in
which the perineal protection device was used, or a control group (n=574), in
which the perineal protection device was not used. The main outcome measurements
were incidence of vaginal and perineal tears (1st to 4th degree tears) and
adverse effects on the parturient and newborn. RESULTS: The incidences of first-
and second-degree tears of the vagina (p=0.018) and perineum (p=0.005) were
significantly reduced in the intervention group compared with the controls. In
the intervention- and control group, 184 women (34.9%) and 142 (26.6%) showed no
perineal tearing, respectively (p=0.034). Numbers needed to treat to avoid any
perianal tearing was 12. The incidence of anal sphincter rupture (ASR) was the
same in both groups (n=19; 3.4%). No negative effects on mother or child from
using the device were observed. CONCLUSIONS: The perineal protective device
significantly reduced the incidence of first- and second-degree tears in the
vagina and perineum during vaginal birth and also significantly increased the
number of parturients with a fully intact posterior commissure. No significant
reduction of ASR and no negative effects of the device were observed.
PMID- 25126979
TI - Single versus multi-dose antibiotic prophylaxis for pelvic organ prolapse surgery
with graft/mesh.
AB - OBJECTIVE: To compare the risk of postoperative infections in women who receive
single-dose versus multi-dose prophylactic antibiotic regimen during prolapse
surgery with mesh/graft. STUDY DESIGN: Retrospective cohort study of 460 women
who underwent prolapse surgery with mesh/graft. We compared women who received a
single-dose prophylactic antibiotic regimen to those who received a multi-dose
regimen. The primary outcome was the presence of any postoperative infection,
defined as the presence of any of the following infections: urinary tract
infection (UTI), fever, wound or trocar site infection, mesh infection or pelvic
abscess. Associations between prophylactic antibiotic regimen and postoperative
infections were estimated using univariable and multivariable analysis. RESULTS:
Rate of any postoperative infection was similar between the single- and multi
dose groups (19% vs. 16%, p=0.50). Rate of UTI was significantly higher in the
single-dose compared to the multi-dose group (13% vs. 7%, p=0.03). On
multivariable analysis, after controlling for vaginal route of surgery, the odds
of UTI was not significantly different between groups (OR 0.59, 95% CI 0.27,
1.26). CONCLUSION: A single-dose antibiotic regimen is sufficient for prophylaxis
against postoperative infections in women undergoing prolapse surgery with
graft/mesh.
PMID- 25126980
TI - Subchorionic hematoma occurs more frequently in in vitro fertilization pregnancy.
AB - OBJECTIVE: Obstetric complications occur more frequently in pregnancies after in
vitro fertilization (IVF). We attempted to determine the correlation between
subchorionic hematoma and IVF pregnancies. STUDY DESIGN: We analyzed 194
pregnancies achieved by infertility treatment between January 2008 and February
2012 at our hospital. Among these, 67 were achieved by IVF and 127 by non-IVF
approaches. We compared the frequency of subchorionic hematoma between the groups
and examined the risk factors for subchorionic hematoma in the IVF group.
RESULTS: No significant differences regarding age and the number of uterine
surgery were observed between the groups. The duration of infertility was longer,
parity and the rate of luteal support were higher in the IVF group compared with
that in the non-IVF group. The frequency of subchorionic hematoma was
significantly higher in the IVF group (22.4%) than that in the non-IVF group
(11%) (P=0.035). Univariate analysis in the IVF group demonstrated that frozen
thawed embryo transfer (OR, 6.18; 95% CI, 1.7-22.4), parity>=1 (OR, 3.67; 95% CI,
1.0-13.2) and blastocyst transfer (OR, 3.75; 95% CI, 1.1-13.3) were risk factors
for the subchorionic hematoma. CONCLUSION: The frequency of subchorionic hematoma
is high in IVF pregnancies, and frozen-thawed embryo transfer, parity>=1, and
blastocyst transfer may contribute to subchorionic hematoma onset.
PMID- 25126981
TI - Maternal and neonatal outcomes in women undergoing bariatric surgery: a
systematic review and meta-analysis.
AB - BACKGROUND: Obese women are at increased risk for many pregnancy complications,
and bariatric surgery (BS) before pregnancy has shown to improve some of these.
OBJECTIVES: To review the current literature and quantitatively assess the
obstetric and neonatal outcomes in pregnant women who have undergone BS. SEARCH
STRATEGY: MEDLINE, EMBASE and Cochrane databases were searched using relevant
keywords to identify studies that reported on pregnancy outcomes after BS.
SELECTION CRITERIA: Pregnancy outcome in firstly, women after BS compared to
obese or BMI-matched women with no BS and secondly, women after BS compared to
the same or different women before BS. Only observational studies were included.
DATA COLLECTION AND ANALYSIS: Two investigators independently collected data on
study characteristics and outcome measures of interest. These were analysed using
the random effects model. Heterogeneity was assessed and sensitivity analysis was
performed to account for publication bias. MAIN RESULTS: The entry criteria were
fulfilled by 17 non-randomised cohort or case-control studies, including seven
with high methodological quality scores. In the BS group, compared to controls,
there was a lower incidence of preeclampsia (OR 0.45, 95% CI 0.25-0.80; P=0.007),
GDM (OR 0.47, 95% CI 0.40-0.56; P<0.001) and large neonates (OR 0.46, 95% CI 0.34
0.62; P<0.001) and a higher incidence of small neonates (OR 1.93, 95% CI 1.52
2.44; P<0.001), preterm birth (OR 1.31, 95% CI 1.08-1.58; P=0.006), admission for
neonatal intensive care (OR 1.33, 95% CI 1.02-1.72; P=0.03) and maternal anaemia
(OR 3.41, 95% CI 1.56-7.44, P=0.002). CONCLUSIONS: BS as a whole improves some
pregnancy outcomes. Laparoscopic adjustable gastric banding does not appear to
increase the rate of small neonates that was seen with other BS procedures. Obese
women of childbearing age undergoing BS need to be aware of these outcomes.
PMID- 25126982
TI - Uterine arteriovenous malformations following gestational trophoblastic
neoplasia: a systematic review.
AB - Uterine arteriovenous malformation (AVM) following gestational trophoblastic
neoplasia (GTN) is a rare condition. It can be associated with chronic vaginal
bleeding or life-threatening heavy bleeding, even after complete resolution of
the tumor following chemotherapy. This analysis aimed to perform an extensive
systematic review highlighting clinical symptoms, imaging, management and
prognosis of this rare complication of GTN. We also describe an additional case
of uterine AVM following GTN. We conducted a literature search using Medline,
Embase and Cochrane library to analyze the clinical data of 49 published cases of
uterine AVM following GTN. Median age of the women diagnosed with AVM was 29
years (range 15-49). Median gravidity was 2 (range 1-8) and 50% of women were
nulligravida. Complete molar pregnancy was the most common initial gestational
trophoblastic diagnosis (48%). Overall, 44 patients (88%) were symptomatic and
presented with chronic or acute abnormal vaginal bleeding. Only 3 patients had an
undetectable HCG level at the time of uterine AVM diagnosis. Hypo-echoic space in
the myometrium is the most relevant finding on ultrasonography but the gold
standard for the definitive diagnosis of AVMs is angiographic examination.
Uterine artery embolization was the most common treatment option performed in 82%
of the patients and was successful in controlling the bleeding in 85% of cases.
We identified 20 pregnancies after successful embolization of uterine AVM
following a GTN and 90% of them were successful. Because of the risk of life
threatening heavy bleeding, the diagnosis of uterine AVM should always be
considered in patients with a history of recurrent unexplained vaginal bleeding
after gestational trophoblastic neoplasia. Angiographic embolization is
successful in the majority of cases and does not appear to compromise future
pregnancy.
PMID- 25126983
TI - [Mediator effect of resilience between burnout and health in nursing staff].
AB - AIMS: To determine the relationships between 3 burnout dimensions (Emotional
Exhaustion, Depersonalization, and Reduced Personal Accomplishment), health
(physical and mental health), and resilience, as well as to analyse the mediator
role of resilience in relationships between burnout and health in a sample of
Nursing staff. METHOD: A correlational and cross-sectional study with
probabilistic sampling was conducted on a sample of 194 Nursing staff of
University Hospital of Fuenlabrada (Madrid), and composed of nurses (n=133) and
nursing assistants (n=61). INSTRUMENTS: MBI-HSS (burnout syndrome), SF-12v1
(physical and mental components of health), 10-Item CD-RISC (resilience), and
sociodemographic variables. RESULTS: Correlational analyses showed that mental
health was negatively related with 3 burnout dimensions and positively with
resilience. Furthermore, physical health was only negatively related with
Emotional Exhaustion, and positively with resilience. Mediational analyses
revealed that resilience mediated, on one hand, the relationship between
Emotional Exhaustion and Depersonalization with mental health (partial mediation)
and, on the other hand, the relationship between Reduced Personal Accomplishment
and mental health (total mediation). CONCLUSIONS: Resilience is not only
important to improve the mental health of Nursing staff, but also to buffer and
minimize the negative consequences of the occupational stress to which they are
at risk, with its most adverse result being signs of burnout. Therefore,
resilience training should be promoted to improve nursing clinical practice.
PMID- 25126984
TI - Identification of catalytic residues of a very large NAD-glutamate dehydrogenase
from Janthinobacterium lividum by site-directed mutagenesis.
AB - We previously found a very large NAD-dependent glutamate dehydrogenase with
approximately 170 kDa subunit from Janthinobacterium lividum (Jl-GDH) and
predicted that GDH reaction occurred in the central domain of the subunit. To
gain further insights into the role of the central domain, several single point
mutations were introduced. The enzyme activity was completely lost in all single
mutants of R784A, K810A, K820A, D885A, and S1142A. Because, in sequence alignment
analysis, these residues corresponded to the residues responsible for glutamate
binding in well-known small GDH with approximately 50 kDa subunit, very large GDH
and well-known small GDH may share the same catalytic mechanism. In addition, we
demonstrated that C1141, one of the three cysteine residues in the central
domain, was responsible for the inhibition of enzyme activity by HgCl2, and HgCl2
functioned as an activating compound for a C1141T mutant. At low concentrations,
moreover, HgCl2 was found to function as an activating compound for a wild-type
Jl-GDH. This suggests that the mechanism for the activation is entirely different
from that for the inhibition.
PMID- 25126985
TI - Identification of newly isolated Talaromyces pinophilus and statistical
optimization of beta-glucosidase production under solid-state fermentation.
AB - Fungi able to degrade agriculture wastes were isolated from different soil
samples, rice straw, and compost; these isolates were screened for their ability
to produce beta-glucosidase. The most active fungal isolate was identified as
Talaromyces pinophilus strain EMOO 13-3. The Plackett-Burman design is used for
identifying the significant variables that influence beta-glucosidase production
under solid-state fermentation. Fifteen variables were examined for their
significances on the production of beta-glucosidase in 20 experimental runs.
Among the variables screened, moisture content, Tween 80, and (NH4)2SO4 had
significant effects on beta-glucosidase production with confidence levels above
90% (p < 0.1). The optimal levels of these variables were further optimized using
Box-Behnken statical design. As a result, the maximal beta-glucosidase activity
is 3648.519 U g(-1), which is achieved at the following fermentation conditions:
substrate amount 0.5 (g/250 mL flask), NaNO3 0.5 (%), KH2PO4 0.3 (%), KCl 0.02
(%), MgSO4 . 7H2O 0.01 (%), CaCl2 0.01 (%), yeast extract 0.07 (%), FeSO4 . 7H2O
0.0002 (%), Tween 80 0.02 (%), (NH4)2SO4 0.3 (%), pH 6.5, temperature 25 degrees
C, moisture content 1 (mL/g dry substrate), inoculum size 0.5 (mL/g dry
substrate), and incubation period 5 days.
PMID- 25126986
TI - Activating PI3-kinase to dampen inflammation.
AB - Diterpene derivatives of the natural product acanthoic acid have potent anti
inflammatory effects in vivo. In this issue of Chemistry & Biolgy, Traves and
colleagues report that the primary molecular mechanism of action of diterpenes
structurally related to acanthoic acid is the direct activation of PI3-kinase
signaling in macrophages, which in turn inhibits NF-kappaB activation and
suppresses proinflammatory gene expression.
PMID- 25126987
TI - Rehabilitating mutant GCase.
AB - Gaucher's disease is a hereditary deficiency of the enzyme beta
glucocerebrosidase (GCase) that is most commonly treated by enzyme replacement
therapy. In this issue of Chemistry & Biology, Tan and colleagues search for
alternative ways to rehabilitate mutant GCase by understanding how it interacts
with the proteostasis network.
PMID- 25126988
TI - Copper as a magic bullet for targeted microbial killing.
AB - The innate toxicity of copper can be exploited as an antimicrobial. In this issue
of Chemistry & Biology Festa and colleagues report the use of QBP, a prochelator
form of the metal-chelate 8-hydroxyquinolone, which allows for targeted copper
dependent microbial killing at sites of infection.
PMID- 25126990
TI - Regulation of nonribosomal peptide synthesis: bis-thiomethylation attenuates
gliotoxin biosynthesis in Aspergillus fumigatus.
AB - Gliotoxin is a redox-active nonribosomal peptide produced by Aspergillus
fumigatus. Like many other disulfide-containing epipolythiodioxopiperazines, a
bis-thiomethylated form is also produced. In the case of gliotoxin,
bisdethiobis(methylthio)gliotoxin (BmGT) is formed for unknown reasons by a
cryptic enzyme. Here, we identify the S-adenosylmethionine-dependent gliotoxin
bis-thiomethyltransferase (GtmA), which converts dithiogliotoxin to BmGT. This
activity, which is induced by exogenous gliotoxin, is only detectable in protein
lysates of A. fumigatus deficient in the gliotoxin oxidoreductase, gliT. Thus,
GtmA is capable of substrate bis-thiomethylation. Deletion of gtmA completely
abrogates BmGT formation and we now propose that the purpose of BmGT formation is
primarily to attenuate gliotoxin biosynthesis. Phylogenetic analysis reveals 124
GtmA homologs within the Ascomycota phylum. GtmA is encoded outside the gliotoxin
biosynthetic cluster and primarily serves to negatively regulate gliotoxin
biosynthesis. This mechanism of postbiosynthetic regulation of nonribosomal
peptide synthesis appears to be quite unusual.
PMID- 25126991
TI - LDAI-based chemical labeling of intact membrane proteins and its pulse-chase
analysis under live cell conditions.
AB - The functions of membrane proteins are tightly controlled by the dynamics such as
protein trafficking and degradation. We demonstrated that ligand-directed acyl
imidazole (LDAI) chemistry is broadly applicable to selective chemical labeling
of various types of membrane-bound proteins under live cell conditions without a
need for any tag fragments. The LDAI chemistry enabled pulse-chase analysis of
these proteins to determine the half-life, as well as their degradation pathways
by the imaging, under almost natural cellular conditions.
PMID- 25126989
TI - ERdj3 is an endoplasmic reticulum degradation factor for mutant
glucocerebrosidase variants linked to Gaucher's disease.
AB - Gaucher's disease (GD) is caused by mutations that compromise beta
glucocerebrosidase (GCase) folding in the endoplasmic reticulum (ER), leading to
excessive degradation instead of trafficking, which results in insufficient
lysosomal function. We hypothesized that ER GCase interacting proteins play
critical roles in making quality control decisions, i.e., facilitating ER
associated degradation (ERAD) instead of folding and trafficking. Utilizing GCase
immunoprecipitation followed by mass-spectrometry-based proteomics, we identified
endogenous HeLa cell GCase protein interactors, including ERdj3, an ER resident
Hsp40 not previously established to interact with GCase. Depleting ERdj3 reduced
the rate of mutant GCase degradation in patient-derived fibroblasts, while
increasing folding, trafficking, and function by directing GCase to the
profolding ER calnexin pathway. Inhibiting ERdj3-mediated mutant GCase
degradation while simultaneously enhancing calnexin-associated folding, by way of
a diltiazem-mediated increase in ER Ca(2+) levels, yields a synergistic rescue of
L444P GCase lysosomal function. Our findings suggest a combination therapeutic
strategy for ameliorating GD.
PMID- 25126992
TI - Alternative sigma factor RpoN2 is required for flagellar motility and full
virulence of Xanthomonas oryzae pv. oryzae.
AB - Xanthomonas oryzae pv. oryzae (Xoo), the bacterial blight pathogen of rice,
harbors a single polar flagellum for motility. How the flagellar system is
regulated and how it is related to bacterial pathogenesis are not well
understood. The genomic sequence of Xoo strain PXO99(A) revealed a flagellar
regulon containing over 60 contiguous genes. A gene encoding alternative sigma
factor 54 (sigma(54)), named as rpoN2, is located in the central region of the
regulon. RT-PCR analysis demonstrated rpoN2 was transcribed in an operon with
flgRR, and fleQ. Single gene deletion mutants of the rpoN2 operon were generated.
The rpoN2 and fleQ mutant lost swimming motility, whereas the flgRR mutant
remained motile. Quantitative RT-PCR analysis further demonstrated that
expression of regulatory genes fliA and flgM, and structural genes flgG, flhB,
and fliC were significantly down-regulated in the rpoN2 and fleQ mutants. These
results indicated that RpoN2 and FleQ synergistically controlled flagellar
motility by regulating gene expression. Interestingly, the rpoN2 mutant, but not
the fleQ mutant was impaired in its virulence on rice. In addition, we showed
that the flagellin gene fliC mutant, which was non-motile, was not defective in
virulence. Thus, we concluded that flagellar motility might not be essential for
Xoo virulence in rice, and RpoN2 probably regulated bacterial virulence through a
manner independent of its role in controlling flagellar gene expression.
PMID- 25126993
TI - Sodium hexadecyl sulfate as an interfacial substance adjusting the adsorption of
a protein on carbon nanotubes.
AB - Carbon nanotubes (CNTs) were functionalized with sodium hexadecyl sulfate (SHS).
The lysozyme adsorbed on the SHS-CNTs exhibited a higher activity than that
immobilized on the nonfunctionalized CNTs. To explain the experimental results
and explore the mechanism of lysozyme adsorption, large-scale molecular dynamics
simulations have been performed for a four-component system, including lysozyme,
SHS, CNTs in explicit water. It has been found that the assembled SHS molecules
form a soft layer on the surface of CNTs. The interactions between lysozyme and
SHS induce the rearrangement of SHS molecules, forming a saddle-like structure on
the CNT surface. The saddle-like structure fits the shape of the lysozyme, and
the active-site cleft of the lysozyme is exposed to the water phase. Whereas, for
the lysozyme adsorbed on the nonfunctionalized CNT, due to the hydrophobic
interactions, the active-site cleft of the enzyme tends to face the wall of the
CNT. The results of this work demonstrate that the SHS molecules as the
interfacial substance have a function of adjusting the lysozyme with an
appropriate orientation, which is favorable for the lysozyme having a higher
activity.
PMID- 25126994
TI - Synthesis of antifungal vaccines by conjugation of beta-1,2 trimannosides with T
cell peptides and covalent anchoring of neoglycopeptide to tetanus toxoid.
AB - Selective strategies for the construction of novel three component glycoconjugate
vaccines presenting Candida albicans cell wall glycan (beta-1,2 mannoside) and
polypeptide fragments on a tetanus toxoid carrier are described. The first of two
conjugation strategies employed peptides bearing an N-terminal thiopropionyl
residue for conjugation to a trisaccharide equipped with an acrylate linker and a
C-terminal S-acetyl thioglycolyl moiety for subsequent linking of neoglycopeptide
to bromoacetylated tetanus toxoid. Michael addition of acrylate trisaccharides to
peptide thiol under mildly basic conditions gave a mixture of N- and C- terminal
glyco-peptide thioethers. An adaptation of this strategy coordinated S-acyl
protection with anticipated thioester exchange equilibria. This furnished a
single chemically defined fully synthetic neoglycopeptide conjugate that could be
anchored to a tetanus toxoid carrier and avoids the introduction of exogenous
antigenic groups. The second strategy retained the N-terminal thiopropionyl
residue but replaced the C-terminal S-acetate functionality with an azido group
that allowed efficient, selective formation of neoglycopeptide thioethers and
subsequent conjugation of these with propargylated tetanus toxoid, but introduced
potentially antigenic triazole linkages.
PMID- 25126995
TI - Human factors/usability barriers to home medical devices among individuals with
disabling conditions: in-depth interviews with positive airway pressure device
users.
AB - BACKGROUND: Evidence suggests that medical equipment often fails to accommodate
the needs of individuals with disabling conditions. Few studies have focused on
the accessibility of home medical devices such as positive airway pressure (PAP),
which is a type of home medical equipment prescribed for long-term therapy.
OBJECTIVE: The purpose of this study was to explore in detail the types of
difficulties experienced by patients with physical/sensory impairments who use
PAP devices, as an initial step in designing a questionnaire to survey users
about this topic. METHODS: In this descriptive study, in-depth interviews were
conducted with 19 participants (9 patients with physical/sensory impairment and
10 health care providers). Interviews were coded and analyzed for major topics.
RESULTS: Participants detailed the numerous ways in which current PAP devices
fail to meet the needs of individuals with physical/sensory impairments (e.g.,
tremor, poor depth perception, paresis), by requiring patients to perform
manually difficult tasks, such as inserting PAP parts through small apertures,
attaching parts using a twisting motion, and lifting arms overhead to apply PAP
headgear. These demands contributed to patients' frustration with and reduced
usage of the home medical device. CONCLUSIONS: Our findings suggest that home
medical devices such as PAP may not be currently designed to meet the needs of
some users with physical/sensory impairments. Additional studies are needed to
measure the prevalence and impact of impairment-related barriers on PAP adherence
for this common medical equipment.
PMID- 25126996
TI - Predictors of loneliness among older women and men in Sweden: A national
longitudinal study.
AB - OBJECTIVES: Longitudinal research on loneliness in old age has rarely considered
loneliness separately for men and women, despite gender differences in life
experiences. The objective of this study was to examine the extent to which older
women and men (70+) report feelings of loneliness with a focus on: (a) changes in
reported loneliness as people age, and (b) which factors predict loneliness.
METHOD: Data from the 2004 and 2011 waves of SWEOLD, a longitudinal national
survey, was used (n = 587). The prediction of loneliness in 2011 by variables
measured in 2004 and 2004-2011 variable change scores was examined in three
logistic regression models: total sample, women and men. Variables in the models
included: gender, age, education, mobility problems, depression, widowhood and
social contacts. RESULTS: Older people moved into and out of frequent loneliness
over time, although there was a general increase in loneliness with age.
Loneliness at baseline, depression increment and recent widowhood were
significant predictors of loneliness in all three multivariable models.
Widowhood, depression, mobility problems and mobility reduction predicted
loneliness uniquely in the model for women; while low level of social contacts
and social contact reduction predicted loneliness uniquely in the model for men.
CONCLUSION: This study challenges the notion that feelings of loneliness in old
age are stable. It also identifies important gender differences in prevalence and
predictors of loneliness. Knowledge about such differences is crucial for the
development of effective policy and interventions to combat loneliness in later
life.
PMID- 25127002
TI - New insights into the role of water in biological function: studying solvated
biomolecules using terahertz absorption spectroscopy in conjunction with
molecular dynamics simulations.
AB - In life science, water is the ubiquitous solvent, sometimes even called the
"matrix of life". There is increasing experimental and theoretical evidence that
solvation water is not a passive spectator in biomolecular processes. New
experimental techniques can quantify how water interacts with biomolecules and,
in doing so, differs from "bulk" water. Terahertz (THz) absorption spectroscopy
has turned out to be a powerful tool to study (bio)molecular hydration. The main
concepts that have been developed in the recent years to describe the underlying
solute-induced sub-picosecond dynamics of the hydration shell are discussed
herein. Moreover, we highlight recent findings that show the significance of
hydrogen bond dynamics for the function of antifreeze proteins and for molecular
recognition. In all of these examples, a gradient of water motion toward
functional sites of proteins is observed, the so-called "hydration funnel". By
means of molecular dynamics simulations, we provide new evidence for a specific
water-protein coupling as the cause of the observed dynamical heterogeneity. The
efficiency of the coupling at THz frequencies is explained in terms of a two-tier
(short- and long-range) solute-solvent interaction.
PMID- 25127003
TI - Implications of marijuana legalization for adolescent substance use.
AB - Marijuana that is legally available for adults has multiple implications for
adolescent substance use. One potential effect that legalization may have is an
increase in adolescent use to due increased availability, greater social
acceptance, and possibly lower prices. Legalization may also facilitate the
introduction of new formulations of marijuana (edible, vaporized) and with
potentially higher potencies. It is unknown what adolescent consumption patterns
will be if marijuana is widely available and marketed in different forms, or what
effects different patterns of adolescent use will have on cognition, the
development of marijuana use disorders, school performance, and the development
of psychotic illnesses. Also unclear is whether adolescent users will be
experiencing higher levels of tetrahydrocannabinol (THC) compared with previous
generations of users due to higher potencies. Although previous studies of the
effects of adolescent marijuana use provide some guidance for current policy and
public health recommendations, many new studies will be needed that answer
questions in the context of use within a legal adult environment. Claims that
marijuana has medicinal benefits create additional challenges for adolescent
prevention efforts, as they contrast with messages of its harmfulness. Prevention
and treatment approaches will need to address perceptions of the safety of
marijuana, claims of its medicinal use, and consider family-wide effects as older
siblings and parents may increasingly openly consume and advocate for marijuana
use. Guidance for primary care physicians will be needed regarded screening and
counseling. Widespread legalization and acceptance of marijuana implies that as
law enforcement approaches for marijuana control decline, public health, medical,
and scientific efforts to understand and reduce negative consequences of
adolescent marijuana use need to be substantially increased to levels
commensurate with those efforts for tobacco and alcohol.
PMID- 25127004
TI - Intertemporal cumulative radiative forcing effects of photovoltaic deployments.
AB - Current policies accelerating photovoltaics (PV) deployments are motivated by
environmental goals, including reducing greenhouse gas (GHG) emissions by
displacing electricity generated from fossil-fuels. Existing practice assesses
environmental benefits on a net life-cycle basis, where displaced GHG emissions
offset those generated during PV production. However, this approach does not
consider that the environmental costs of GHG release during production are
incurred early, while environmental benefits accrue later. Thus, where policy
targets suggest meeting GHG reduction goals established by a certain date, rapid
PV deployment may have counterintuitive, albeit temporary, undesired
consequences. On a cumulative radiative forcing (CRF) basis, the environmental
improvements attributable to PV might be realized much later than is currently
understood, particularly when PV manufacturing utilizes GHG-intensive energy
sources (e.g., coal), but deployment occurs in areas with less GHG-intensive
electricity sources (e.g., hydroelectric). This paper details a dynamic CRF model
to examine the intertemporal warming impacts of PV deployments in California and
Wyoming. CRF payback times are longer than GHG payback times by 6-12 years in
California and 6-11 years in Wyoming depending on the PV technology mix and
deployment strategy. For the same PV capacity being deployed, early installations
yield greater CRF benefits (calculated over 10 and 25 years) than installations
occurring later in time. Further, CRF benefits are maximized when PV technologies
with the lowest manufacturing GHG footprint (cadmium telluride) are deployed in
locations with the most GHG-intensive grids (i.e., Wyoming).
PMID- 25127005
TI - Using ROC to examine the association between attendance and compliance.
PMID- 25127006
TI - Fabrication of boron nitride nanotube-gold nanoparticle hybrids using pulsed
plasma in liquid.
AB - Plasma, generated in liquid at atmospheric pressure by a nanosecond pulsed
voltage, was used to fabricate hybrid structures from boron nitride nanotubes and
gold nanoparticles in deionized water. The pH was greatly reduced, conductivity
was significantly increased, and concentrations of reactive oxygen and nitrogen
species in the water were increased by the plasma treatment. The treatment
reduced the length of the nanotubes, giving more individual cuplike structures,
and introduced functional groups onto the surface. Gold nanoparticles were
successively assembled onto the functionalized surfaces. The reactive species
from the liquid plasma along with the nanosecond pulsed electric field seem to
play a role in the shortening and functionalization of the nanotubes and the
assembly of gold nanoparticles. The potential for targeted drug delivery was
tested in a preliminary investigation using doxorubicin-loaded plasma-treated
nanotubes which were effective at killing ~99% of prostate cancer cells.
PMID- 25127007
TI - Growth and anaerobic digestion characteristics of microalgae cultivated using
various types of sewage.
AB - Microalgal cultivation combined with anaerobic digestion at wastewater treatment
plants is promising to recover energy. This study investigated the growth and
anaerobic digestion characteristics of microalgae cultivated using nutrients in
sewage. Microalgae were cultivated using primary effluent, secondary effluent,
and dewatering filtrate. Microscopic observation indicated that Chlorella was
cultivated using dewatering filtrate of anaerobic digestion without controlling
the type of species. Batch anaerobic digestion experiments with digested sludge
showed that the methane conversion ratio of the cultivated mixture was
approximately 40-65%. Different cultivation time did not affect the microalgal
contents. Methane recovery mass was 0.13NL-methane/L-cultivation liquor. The C/N
ratio of the cultivated mixture was approximately 3-5, but the apparent ammonia
release ratio was smaller than that of sewage sludge during digestion. These
results proved the applicability of methane recovery from microalgae cultivated
using nutrients included in anaerobically digested sludge.
PMID- 25127008
TI - Performance of the lysozyme for promoting the waste activated sludge
biodegradability.
AB - The fresh waste activated sludge (WAS) from a lab-scale sequencing batch reactor
was used to determine the performance of the lysozyme for promoting its
biodegradability. The results showed that a strict linear relationship presented
between the degree of disintegration (DDM) of WAS and the lysozyme incubation
time from 0 to 240min (R(2) was 0.992, 0.995 and 0.999 in accordance with the
corresponding lysozyme/TS, respectively). Ratio of net SCOD increase augmented
significantly by lysozyme digestion for evaluating the sludge biodegradability
changes. Moreover, the protein dominated both in the EPS and SMP. In addition,
the logarithm of SMP contents in supernatant presented an increasing trend
similar with the ascending logarithmic relation with the lysozyme incubation time
from 0 to 240min (R(2) was 0.960, 0.959 and 0.947, respectively). The SMP,
especially the soluble protein, had an important contribution to the improvement
of WAS biodegradability.
PMID- 25127009
TI - Enhanced succinic acid production and magnesium utilization by overexpression of
magnesium transporter mgtA in Escherichia coli mutant.
AB - In this study, a novel engineered Escherichia coli strain KMG111 was constructed
by overexpression of mgtA in E. coli mutant DC1515. By adopting KMG111, nearly a
concentration of succinic acid (32.41gL(-1)) with a yield of 0.81gg(-1) glucose,
could be obtained in a batch fermentation by using the low-cost mixture of
Mg(OH)2 and NH3.H2O to replace MgCO3 as the alkaline neutralizer. Moreover, the
effect of the inhibitory compounds in lignocellulosic hydrolyzates on cell growth
and succinic acid production could be relieved. In a 3-L bioreactor, the overall
productivity and yield of succinic acid in the whole anaerobic stage were 2.15gL(
1)h(-1) and 0.86gg(-1) total sugar, respectively. This study was the first to
report decreased alkaline neutralizer cost via genetic manipulation for succinic
acid production, which contributed to the industrialization of this microbial
synthesis process.
PMID- 25127010
TI - Upgrading the rice husk char obtained by flash pyrolysis for the production of
amorphous silica and high quality activated carbon.
AB - The overall valorization of rice husk char obtained by flash pyrolysis in a
conical spouted bed reactor (CSBR) has been studied in a two-step process. Thus,
silica has been recovered in a first step and the remaining carbon material has
been subjected to steam activation. The char samples used in this study have been
obtained by continuous flash pyrolysis in a conical spouted bed reactor at 500
degrees C. Extraction with Na2CO3 allows recovering 88% of the silica contained
in the rice husk char. Activation of the silica-free rice husk char has been
carried out in a fixed bed reactor at 800 degrees C using steam as activating
agent. The porous structure of the activated carbons produced includes a
combination of micropores and mesopores, with a BET surface area of up to
1365m(2)g(-1) at the end of 15min.
PMID- 25127012
TI - Serum adipocyte fatty acid binding protein levels are positively associated with
subclinical atherosclerosis in Chinese pre- and postmenopausal women with normal
glucose tolerance.
AB - CONTEXT: Recent studies highlight a critical interaction between adipocyte fatty
acid binding protein (A-FABP) and cardiovascular disorders. However, associations
of A-FABP with subclinical atherosclerosis in a population with normal glucose
tolerance remain unknown. OBJECTIVE: The study aimed to evaluate the relationship
between A-FABP and carotid intima-media thickness (C-IMT) in a Chinese population
with normal glucose tolerance. DESIGN AND SETTING: A cross-sectional analysis was
conducted of 2253 cardiovascular disease-free normal glucose tolerance subjects
(835 men, 1418 women; 20-78 years old) from the Shanghai Obesity Study. MAIN
OUTCOME AND MEASURES: C-IMT was measured by B-mode ultrasound and used to assess
subclinical atherosclerosis. Serum A-FABP levels were quantified by a sandwich
ELISA. RESULTS: The median serum level for A-FABP was 4.0 ng/mL (interquartile
range: 2.6-6.0 ng/mL), and significantly higher in women than men (P < .001).
After adjusting for age and body mass index (BMI), a partial correlation analysis
showed that A-FABP levels correlated with C-IMT in men, premenopausal, and
postmenopausal women (P = .024, .006, and .016, respectively). Furthermore, C-IMT
increased along with quartile A-FABP values (all P for trend <.001). Regression
analyses demonstrated that A-FABP was associated with C-IMT only in women (P =
.044 and .001 for pre- and postmenopausal, respectively). Moreover, A-FABP was
identified as a risk factor for C-IMT in pre- and postmenopausal women with a
normal BMI (P < .001 and P = .012, respectively). CONCLUSIONS: Serum A-FABP
levels independently and positively correlate with subclinical atherosclerosis in
pre- and postmenopausal Chinese women with normal glucose tolerance after
adjustments for the traditional risk factors.
PMID- 25127011
TI - A model of BMD changes after alendronate discontinuation to guide postalendronate
BMD monitoring.
AB - CONTEXT: Women stopping alendronate are commonly monitored with serial bone
mineral density (BMD) measurements, yet no information exists on how frequently
or for whom these measurements should be performed. OBJECTIVE: The objective of
the study was to develop a tool to guide post-alendronate BMD monitoring. DESIGN:
A predictive model was constructed to estimate the time until a given percentage
of women's BMD T-scores drop below a given threshold that indicates a management
change (such as retreatment) would be considered. This model was then used to
estimate the time it would take for groups of women defined by their baseline
BMDs to drop below the given threshold. SETTING: Data were derived from the
Fracture Intervention Trial Long Term Extension (FLEX), the largest multicenter
clinical trial of its type to date. PARTICIPANTS: Four hundred four women who had
received an average of 5.1 years of alendronate during the Fracture Intervention
Trial and were subsequently observed for 5 treatment-free years (on placebo)
during the FLEX trial were used to estimate the change in BMD over time. RESULTS:
If a management change such as alendronate reinitiation would be considered when
BMD T-score drops below -2.5, the model shows that women with total hip BMD
greater than -1.9 T-scores at the time of alendronate discontinuation have less
than a 20% probability that at follow-up, monitoring BMD will be below the
threshold within 5 years. The model performed similarly, and results are provided
over a range of management change thresholds from -1.75 to -3 T-scores.
CONCLUSIONS: Using the tool developed in this analysis, it is possible to
estimate when BMD repeat measurement after alendronate discontinuation could
potentially be useful. Measuring BMD within 5 years after alendronate
discontinuation is unlikely to change management for women with total hip BMD 0.6
T-scores above a prespecified retreatment threshold within the range of -1.75 to
3 T-scores.
PMID- 25127014
TI - A dynamic duo: pairing click chemistry and postpolymerization modification to
design complex surfaces.
AB - Advances in key 21st century technologies such as biosensors, biomedical
implants, and organic light-emitting diodes rely heavily on our ability to
imagine, design, and understand spatially complex interfaces. Polymer-based thin
films provide many advantages in this regard, but the direct synthesis of
polymers with incompatible functional groups is extremely difficult. Using
postpolymerization modification in conjunction with click chemistry can
circumvent this limitation and result in multicomponent surfaces that are
otherwise unattainable. The two methods used to form polymer thin films include
physisorption and chemisorption. Physisorbed polymers suffer from instability
because of the weak intermolecular forces between the film and the substrate,
which can lead to dewetting, delamination, desorption, or displacement. Covalent
immobilization of polymers to surfaces through either a "grafting to" or
"grafting from" approach provides thin films that are more robust and less prone
to degradation. The grafting to technique consists of adsorbing a polymer
containing at least one reactive group along the backbone to form a covalent bond
with a complementary surface functionality. Grafting from involves polymerization
directly from the surface, in which the polymer chains deviate from their native
conformation in solution and stretch away from the surface because of the high
density of chains. Postpolymerization modification (PPM) is a strategy used by
our groups over the past several years to immobilize two or more different
chemical functionalities onto substrates that contain covalently grafted polymer
films. PPM exploits monomers with reactive pendant groups that are stable under
the polymerization conditions but are readily modified via covalent attachment of
the desired functionality. "Click-like" reactions are the most common type of
reactions used for PPM because they are orthogonal, high-yielding, and rapid.
Some of these reactions include thiol-based additions, activated ester coupling,
azide-alkyne cycloadditions, some Diels-Alder reactions, and non-aldol carbonyl
chemistry such as oxime, hydrazone, and amide formation. In this Account, we
highlight our research combining PPM and click chemistry to generate complexity
in polymer thin films. For the purpose of this Account, we define a complex
coating as a polymer film grafted to a planar surface that acts as a template for
the patterning of two or more discrete chemical functionalities using PPM. After
a brief introduction to grafting, the rest of the review is arranged in terms of
the sequence in which PPM is performed. First, we describe sequential
functionalization using iterations of the same click-type reaction. Next, we
discuss the use of two or more different click-like reactions performed
consecutively, and we conclude with examples of self-sorting reactions involving
orthogonal chemistries used for one-pot surface patterning.
PMID- 25127013
TI - Association between anticoagulant treatment duration and risk of venous
thromboembolism recurrence and bleeding in clinical practice.
AB - INTRODUCTION: This retrospective observational study examined whether
anticoagulant treatment duration varies by risks of venous thromboembolism (VTE)
recurrence and bleeding. MATERIALS AND METHODS: VTE patients naive to
anticoagulants were identified from the HealthCore Integrated Research Database
between 06/01/2007 and 09/30/2011 and categorized into three groups: provoked,
cancer-related, and unprovoked VTE. Treatment duration was from initiation to
discontinuation of anticoagulation, based on a 60-day gap in prescription fill
unless there was an international normalized ratio test every 42 days. Bleeding
risk was estimated using RIETE score, and VTE risk categories were based on ACCP
guidelines. Kaplan-Meier curves and Cox proportional hazards models were used to
evaluate association between VTE recurrence/bleeding and anticoagulation
duration. RESULTS: Of 2002 patients identified (52.3% males, mean age 57 +/-15
years), 21.4% had provoked, 16.4% had cancer-related, and 62.1% had unprovoked
VTE. Average anticoagulant treatment duration was 294 +/- 261 days. After
adjusting for demographics and clinical characteristics, provoked and cancer
related VTE patients were 32% (95% CI=14-54%, P<0.001) and 35% (95% CI=7-70%,
P=0.013) more likely, respectively, to discontinue anticoagulants than unprovoked
VTE patients. No differences were observed between provoked and cancer-related
VTE patients. Patients with an intermediate/high bleeding risk were 26% (95%
CI=14-36%, P<0.001) less likely to discontinue treatment than those with a low
bleeding risk. CONCLUSIONS: The observed anticoagulation duration for VTE may not
be concordant with guidelines, due to the challenge of counterbalancing risks of
VTE recurrence and bleeding. Further studies are needed to explore this.
PMID- 25127015
TI - Is the exoproteome important for bacterial pathogenesis? Lessons learned from
interstrain exoprotein diversity in Listeria monocytogenes grown at different
temperatures.
AB - Bacterial exoproteomes vary in composition and quantity among species and within
each species, depending on the environmental conditions to which the cells are
exposed. This article critically reviews the literature available on exoproteins
synthesized by the foodborne pathogenic bacterium Listeria monocytogenes grown at
different temperatures. The main challenges posed for exoproteome analyses and
the strategies that are being used to overcome these constraints are discussed.
Over thirty exoproteins from L. monocytogenes are considered, and the
multifunctionality of some of them is discussed. Thus, at the host temperature of
37 degrees C, good examples are provided by Lmo0443, a potential marker for low
virulence, and by the virulence factors internalin C (InlC) and listeriolysin O
(LLO). Based on the reported LLO-induced mucin exocytosis, a model is proposed
for the involvement of extracellular LLO in optimizing the conditions for InlC
intervention in the invasion of intestinal epithelial cells. At lower growth
temperatures, exoproteins such as flagellin (FlaA) and oligopeptide permease
(OppA) may explain the persistence of particular strains in the food industry
environment, eventually allowing the development of new tools to eradicate L.
monocytogenes, a major concern for public health.
PMID- 25127016
TI - Regulation of lipid metabolism in the green microalga Chlorella protothecoides by
heterotrophy-photoinduction cultivation regime.
AB - Proteomics in conjunction with biochemical strategy was employed to unravel
regulation of lipid metabolism in the green microalga Chlorella protothecoides by
heterotrophy-photoinduction cultivation regime (HPC). Interestingly, HPC
triggered transiently synthesis of starch followed by substantial lipid
accumulation. And a marked decrease in intracellular protein and chlorophyll
contents was also observed after 12h of photo-induction. The highest lipid
content of 50.5% was achieved upon the photo-induction stage, which represented
69.3% higher than that of the end of heterotrophic cultivation. Results suggested
that turnover of carbon-nitrogen-rich compounds such as starch, protein, and
chlorophyll might provide carbon or energy for lipid accumulation. The proteomics
analysis indicated that several pathways including glycolysis, TCA cycle, beta
oxidation of fatty acids, Calvin cycle, photosynthesis, energy and transport,
protein biosynthesis, regulate and defense were involved in the lipid
biosynthesis. Malate dehydrogenase and acyl-CoA dehydrogenase were suggested as
key regulatory factors in enhancing lipid accumulation.
PMID- 25127018
TI - Copper-catalyzed direct alkylation of 1,3-azoles with N-tosylhydrazones bearing a
ferrocenyl group: a novel method for the synthesis of ferrocenyl-based ligands.
AB - Copper-catalyzed cross-coupling of ferrocenyl ketone-derived N-tosylhydrazones
with benzo[d]oxazole leads to the direct C-H bond functionalization by a
secondary ferrocenyl alkyl group. This direct C-H bond alkylation of azoles with
N-tosylhydrazones bearing a ferrocenyl group uses inexpensive CuBr as the
catalyst without any ligand. The reaction is operationally simple and conducted
under mild conditions, giving the corresponding ferrocenyl-based ligands in
moderate to good yields. Furthermore, they were able to act as bidentate ligands,
giving rise to the corresponding palladium chelated complex 6a-6c, which were
obtained by reaction of 5a-5c with [PdCl2(MeCN)2].
PMID- 25127017
TI - HIV-1 replication in human immune cells is independent of TAR DNA binding protein
43 (TDP-43) expression.
AB - The TAR DNA binding protein (TDP-43) was originally identified as a host cell
factor binding to the HIV-1 LTR and thereby suppressing HIV-1 transcription and
gene expression (Ou et al., J.Virol. 1995, 69(6):3584). TDP-43 is a global
regulator of transcription, can influence RNA metabolism in many different ways
and is ubiquitously expressed. Thus, TDP-43 could be a major factor restricting
HIV-1 replication at the level of LTR transcription and gene expression. These
facts prompted us to revisit the role of TDP-43 for HIV-1 replication. We
utilized established HIV-1 cell culture systems as well as primary cell models
and performed a comprehensive analysis of TDP-43 function and investigated its
putative impact on HIV-1 gene expression. In HIV-1 infected cells TDP-43 was
neither degraded nor sequestered from the nucleus. Furthermore, TDP-43
overexpression as well as siRNA mediated knockdown did not affect HIV-1 gene
expression and virus production in T cells and macrophages. In summary, our
experiments argue against a restricting role of TDP-43 during HIV-1 replication
in immune cells.
PMID- 25127019
TI - Meroterpenes from Psoralea corylifolia against Pyricularia oryzae.
AB - Six new meroterpenes, namely, 13-methoxyisobakuchiol (1), 13-ethoxyisobakuchiol
(2), 12,13-dihydro-13-hydroxybakuchiol (3), Delta(10)-12,13-dihydro-12-(R,S)
methoxyisobakuchiol (4 and 5), and 15-demetyl-12,13-dihydro-13-ketobakuchiol (6),
together with four known ones, namely, Delta(3),2-hydroxybakuchiol (7),
Delta(1),3-hydroxybakuchiol (8), bakuchiol (9), and Delta(1,3)-bakuchiol (10),
were isolated from the seeds of Psoralea corylifolia. Their structures were
identified based on spectral data, including those obtained via 1D and 2D NMR,
and MS spectral analyses. Antifungal screening results indicated that all
compounds showed moderate inhibitory activities against Pyricularia oryzae.
PMID- 25127020
TI - Antihyperlipidemic effects of rhapontin and rhapontigenin from rheum undulatum in
rats fed a high-cholesterol diet.
AB - Rhapontin was purified from a methanol extract from the roots of Rheum undulatum,
and rhapontigenin was produced by an enzymatic transformation of rhapontin. Rats
were fed a high-cholesterol diet to induce hyperlipidemia, followed by oral
treatment with rhapontin or rhapontigenin (1-5 mg/kg/day). Rhapontin and
rhapontigenin treatment resulted in a significant (p<0.05) dose-dependent
decrease in the serum lipid level, while the high-density lipoprotein cholesterol
level increased slightly compared with the experimental control. Furthermore,
rhapontin and rhapontigenin treatment improved the pathological characteristics
of the degenerating fatty liver in high-cholesterol diet-induced hyperlipidemic
rats dose-dependently. Aspartate aminotransferase and alanine aminotransferase
levels in rhapontin- and rhapontigenin-treated hyperlipidemic rats were not
significantly different from those in the control. These results indicate that
rhapontin and rhapontigenin can be used as potent antihyperlipidemic agents.
PMID- 25127021
TI - Amide alkaloids from Scopolia tangutica.
AB - Four new hydroxycinnamic acid amides, scotanamines A-D (1-4), and seven known
alkaloids, including N (1),N (10)-di-dihydrocaffeoylspermidine (5), scopolamine
(6), anisodamine (7), hyoscyamine (8), anisodine (9), caffeoylputrescine (10),
and N (1)-caffeoyl-N (3)-dihydrocaffeoylspermidine (11), were obtained from the
roots of Scopolia tangutica. The present study represents the first recognition
of hydroxycinnamic acid amides containing putrescine or spermidine in S.
tangutica. Compound 1, in particular, contains a moiety resulting from the
condensation of nortropinone and putrescine. Compound 2 exhibited moderate
agonist activity at the u-opioid receptor (EC50=7.3 uM). Compound 2 was tested in
vivo and induced analgesia in mice. The analgesic effect was recorded using the
tail-flick assay and was reversed by naloxone.
PMID- 25127022
TI - Isolation, characterization, and antitumor activity of a novel heteroglycan from
cultured mycelia of Cordyceps sinensis.
AB - A novel heteroglycan, Cordyceps sinensis polysaccharide 1 (molecular weight 1 17
* 10(5) Da), was isolated and purified from mycelia of the fungus C. sinensis
obtained by solid-state culture. Structural characterization by chemical
analysis, GC-MS, FTIR, and NMR spectroscopy showed that C. sinensis
polysaccharide 1 was mainly composed of (1 -> 6)-linked alpha-D-Glc and alpha-D
Gal, with minor beta-(1 -> 4)-D-Xyl and beta-(1 -> 4)-D-Man residues probably
located in the side chains with a trace amount of alpha-(1 -> 3)-L-Rha residue.
In biological assays, C. sinensis polysaccharide 1 significantly inhibited
proliferation of sarcoma 180 cells and induced apoptosis in a dose-dependent
manner. Further studies will elucidate the antitumor mechanism of C. sinensis
polysaccharide 1 and promote its utilization for the development of novel,
effective anticancer drugs.
PMID- 25127024
TI - Fumigaclavines D-H, new ergot alkaloids from endophytic Aspergillus fumigatus.
AB - Ergot alkaloids are toxins which are produced biotechnologically on an industrial
scale. The chemical investigation of endophytic Aspergillus fumigatus resulted in
the isolation of five new ergot alkaloids named fumigaclavines D-H (2-6), along
with three known analogues, fumigaclavine C (1), festuclavine (7), and
fumigaclavine A (8). Their structures were unequivocally elucidated by extensive
spectroscopic analyses in association with X-ray single-crystal diffraction.
Fumigaclavines D-H are interesting clavine-type ergot alkaloids featuring a
reverse prenyl moiety at C-2, with 1-4, 6, and 8 bearing additional substituents,
e.g., an OH or OAc group at C-9. Compounds 2, 4, and 6-8 showed a broad spectrum
of antimicrobial activity against a panel of anaerobic microorganisms, of which
compounds 4 and 6 were the most active against Veillonella parvula with an MIC=16
ug/mL compared to that (0.12 ug/mL) of tinidazole, co-assayed as a positive
reference.
PMID- 25127023
TI - Chemical composition and biological effects of Artemisia maritima and Artemisia
nilagirica essential oils from wild plants of western Himalaya.
AB - Artemisia species possess pharmacological properties that are used for medical
purposes worldwide. In this paper, the essential oils from the aerial parts of
Artemisia nilagirica and Artemisia maritima from the western Indian Himalaya
region are described. The main compounds analyzed by simultaneous GC/MS and
GC/FID were camphor and 1,8-cineole from A. maritima, and camphor and artemisia
ketone from A. nilagirica. Additionally, the oils were evaluated for their
antibacterial, antifungal, mosquito biting deterrent, and larvicidal activities.
A. nilagirica essential oil demonstrated nonselective antifungal activity against
plant pathogens Colletotrichum acutatum, Colletotrichum fragariae, and
Colletotrichum gloeosporioides, whereas A. maritima did not show antifungal
activity. Both Artemisia spp. exhibited considerable mosquito biting deterrence,
whereas only A. nilagirica showed larvicidal activity against Aedes aegypti.
Antibacterial effects assessed by an agar dilution assay demonstrated greater
activity of A. maritima essential oil against Staphylococcus aureus and
Pseudomonas aeruginosa compared to A. nilagirica.
PMID- 25127025
TI - Effective treatment of invasive Aspergillus fumigatus infection using
combinations of topical and systemic antifungals in a severely burned patient.
AB - The authors describe an invasive Aspergillus fumigatus deep-burn wound infection
in a severely burned patient that was successfully treated with a combination of
topical terbinafine and systemic voriconazole antifungal therapy. To our
knowledge, this is the first case report describing the effective control of an
invasive deep-burn wound infection using this combination.
PMID- 25127026
TI - The effects of intravenous vitamin C on point-of-care glucose monitoring.
AB - Ascorbic acid (vitamin C) decreases systemic inflammation and lowers fluid
requirements after thermal injury; therefore it has been adopted in many burn
centers as an adjunct to resuscitation. However, recent concerns have been
expressed over clinically significant hypoglycemic events caused by vitamin C
interference with the point-of-care (POC) glucose measurements. This case series
presents a direct comparison of POC and laboratory reference glucose values in
the patients receiving vitamin C infusion. Vitamin C was administered at 66
mg/kg/hour in seven patients with burns >30% TBSA. The baseline characteristics
and burn characteristics were recorded. POC glucose measurements were made with a
commonly used hand-held device, and the laboratory values were obtained using
standard spectrophotometric methods. POC and laboratory glucose values drawn
within the same hour were compared. Hemoglobin, which is known to cause
interference in POC testing, was also recorded. All the patients demonstrated
falsely elevated POC glucose values during and/or immediately after the infusion
period, with discrepancies ranging from 10 to 200 mg/dl. These findings were
irregular, unpredictable and unrelated to hemoglobin levels. The findings suggest
an idiosyncratic reaction that cannot be easily corrected at the bedside using
mathematical equations. POC glucose monitoring should be avoided during and after
vitamin C therapy.
PMID- 25127028
TI - Delirium screening anchored in child development: The Cornell Assessment for
Pediatric Delirium.
AB - OBJECTIVE: The recently validated Cornell Assessment for Pediatric Delirium
(CAPD) is a new rapid bedside nursing screen for delirium in hospitalized
children of all ages. The present manuscript provides a "developmental anchor
points" reference chart, which helps ground clinicians' assessment of CAPD
symptom domains in a developmental understanding of the presentation of delirium.
METHOD: During the development of this CAPD screening tool, it became clear that
clinicians need specific guidance and training to help them draw on their
expertise in child development and pediatrics to improve the interpretative
reliability of the tool and its accuracy in diagnosing delirium. The
developmental anchor points chart was formulated and reviewed by a
multidisciplinary panel of experts to evaluate content validity and include
consideration of sick behaviors within a hospital setting. RESULTS: The CAPD
developmental anchor points for the key ages of newborn, 4 weeks, 6 weeks, 8
weeks, 28 weeks, 1 year, and 2 years served as the basis for training bedside
nurses in scoring the CAPD for the validation trial and as a multifaceted bedside
reference chart to be implemented within a clinical setting. In the current
paper, we discuss the lessons learned during implementation, with particular
emphasis on the importance of collaboration with the bedside nurse, the
challenges of establishing a developmental baseline, and further questions about
delirium diagnosis in children. SIGNIFICANCE OF RESULTS: The CAPD with
developmental anchor points provides a validated, structured, and developmentally
informed approach to screening and assessment of delirium in children. With
minimal training on the use of the tool, bedside nurses and other pediatric
practitioners can reliably identify children at risk for delirium.
PMID- 25127027
TI - Loss of Intralipid(r)- but not sevoflurane-mediated cardioprotection in early
type-2 diabetic hearts of fructose-fed rats: importance of ROS signaling.
AB - BACKGROUND: Insulin resistance and early type-2 diabetes are highly prevalent.
However, it is unknown whether Intralipid(r) and sevoflurane protect the early
diabetic heart against ischemia-reperfusion injury. METHODS: Early type-2
diabetic hearts from Sprague-Dawley rats fed for 6 weeks with fructose were
exposed to 15 min of ischemia and 30 min of reperfusion. Intralipid(r) (1%) was
administered at the onset of reperfusion. Peri-ischemic sevoflurane (2 vol.-%)
served as alternative protection strategy. Recovery of left ventricular function
was recorded and the activation of Akt and ERK 1/2 was monitored. Mitochondrial
function was assessed by high-resolution respirometry and mitochondrial ROS
production was measured by Amplex Red and aconitase activity assays.
Acylcarnitine tissue content was measured and concentration-response curves of
complex IV inhibition by palmitoylcarnitine were obtained. RESULTS: Intralipid(r)
did not exert protection in early diabetic hearts, while sevoflurane improved
functional recovery. Sevoflurane protection was abolished by concomitant
administration of the ROS scavenger N-2-mercaptopropionyl glycine. Sevoflurane,
but not Intralipid(r) produced protective ROS during reperfusion, which activated
Akt. Intralipid(r) failed to inhibit respiratory complex IV, while sevoflurane
inhibited complex I. Early diabetic hearts exhibited reduced carnitine-palmitoyl
transferase-1 activity, but palmitoylcarnitine could not rescue protection and
enhance postischemic functional recovery. Cardiac mitochondria from early
diabetic rats exhibited an increased content of subunit IV-2 of respiratory
complex IV and of uncoupling protein-3. CONCLUSIONS: Early type-2 diabetic hearts
lose complex IV-mediated protection by Intralipid(r) potentially due to a switch
in complex IV subunit expression and increased mitochondrial uncoupling, but are
amenable to complex I-mediated sevoflurane protection.
PMID- 25127030
TI - Catheter ablation for atrial fibrillation after an unsuccessful surgical ablation
and biological prosthetic mitral valve replacement: a pilot study.
AB - BACKGROUND: Patients with mitral valve (MV) disease and atrial fibrillation (AF)
undergo simultaneous prosthetic valve replacement and radiofrequency (RF)
ablation procedure; however, this combinational procedure restores sinus rhythm
(SR) in only 68-82% of the cases. In patients with ineffective surgical ablation,
the use of a biological prosthetic valve might not only be a good choice to
perform safe catheter ablation procedure in the left atrium (LA), but also
provide a way to discontinue administration of oral anticoagulants. The objective
of this study was to assess the efficacy of catheter ablation for AF after MV
replacement with a biological prosthesis and an ineffective surgical ablation
procedure. METHODS: Ten consecutive patients aged 48 +/- 7 years were enrolled in
this study. All patients had long-persistent AF associated with a rheumatic valve
disease, which was treated by MV replacement with a biological prosthesis and a
surgical RF ablation procedure. In the late postoperative period, all the
patients had recurrent hemodynamically significant AF, which required repeated
cardioversions. From 1 year to 3 years after the surgery, catheter ablation was
performed, including reisolation of pulmonary veins (PVs) with the ablation of
ganglionic plexi or linear lesions on the roof of the LA and mitral isthmus. The
efficacy was assessed at 3 months, 6 months, and 12 months after the procedure.
RESULTS: Restoration of SR during ablation was achieved in all of the cases. In 6
9 months, all the patients were free of arrhythmia. LA stunning manifested by the
absence or decrease of the "A" wave in the transmitral flow and the retrograde
wave in the PV flow was observed in nine patients with SR. In five of the
patients, LA contractile function was restored in 1-6 months. Prosthetic valve
dysfunction was not detected in any of the patients. CONCLUSION: Catheter
ablation is an effective method for AF treatment following an ineffective
surgical RF ablation procedure and biological prosthetic MV replacement. The use
of bioprosthetic MVs allows for performing safe catheter ablation without
subsequent prosthetic dysfunction.
PMID- 25127029
TI - Increased expression of chemerin in squamous esophageal cancer myofibroblasts and
role in recruitment of mesenchymal stromal cells.
AB - Stromal cells such as myofibroblasts influence tumor progression. The mechanisms
are unclear but may involve effects on both tumor cells and recruitment of bone
marrow-derived mesenchymal stromal cells (MSCs) which then colonize tumors. Using
iTRAQ and LC-MS/MS we identified the adipokine, chemerin, as overexpressed in
esophageal squamous cancer associated myofibroblasts (CAMs) compared with
adjacent tissue myofibroblasts (ATMs). The chemerin receptor, ChemR23, is
expressed by MSCs. Conditioned media (CM) from CAMs significantly increased MSC
cell migration compared to ATM-CM; the action of CAM-CM was significantly reduced
by chemerin-neutralising antibody, pretreatment of CAMs with chemerin siRNA,
pretreatment of MSCs with ChemR23 siRNA, and by a ChemR23 receptor antagonist,
CCX832. Stimulation of MSCs by chemerin increased phosphorylation of p42/44, p38
and JNK-II kinases and inhibitors of these kinases and PKC reversed chemerin
stimulated MSC migration. Chemerin stimulation of MSCs also induced expression
and secretion of macrophage inhibitory factor (MIF) that tended to restrict
migratory responses to low concentrations of chemerin but not higher
concentrations. In a xenograft model consisting of OE21 esophageal cancer cells
and CAMs, homing of MSCs administered i.v. was inhibited by CCX832. Thus,
chemerin secreted from esophageal cancer myofibroblasts is a potential
chemoattractant for MSCs and its inhibition may delay tumor progression.
PMID- 25127032
TI - Glioma-derived ADAM10 induces regulatory B cells to suppress CD8+ T cells.
AB - CD8+ T cells play an important role in the anti-tumor activities of the body. The
dysfunction of CD8+ T cells in glioma is unclear. This study aims to elucidate
the glioma cell-derived ADAM10 (A Disintegrin and metalloproteinase domain
containing protein 10) in the suppression of CD8+ effector T cells by the
induction of regulatory B cells. In this study, glioma cells were isolated from
surgically removed glioma tissue and stimulated by Phorbol myristate acetage
(PMA) in the culture. The levels of ADAM10 in the culture were determined by
enzyme-linked immunosorbent assay. Immune cells were assessed by flow cytometry.
The results showed that the isolated glioma cells express ADAM10, which was
markedly up regulated after stimulated with PMA. The glioma-derived ADAM10
induced activated B cells to differentiate into regulatory B cells, the later
suppressed CD8+ T cell proliferation as well as the induced regulatory T cells,
which also showed the immune suppressor effect on CD8+ effector T cell
proliferation. In conclusion, glioma cells produce ADAM10 to induce Bregs; the
latter suppresses CD8+ T cells and induces Tregs.
PMID- 25127031
TI - Sequestering HMGB1 via DNA-conjugated beads ameliorates murine colitis.
AB - Inflammatory bowel disease (IBD) is chronic inflammation of the gastrointestinal
tract that affects millions of people worldwide. Although the etiology of IBD is
not clear, it is known that products from stressed cells and enteric microbes
promote intestinal inflammation. High mobility group box 1 (HMGB1), originally
identified as a nuclear DNA binding protein, is a cytokine-like protein mediator
implicated in infection, sterile injury, autoimmune disease, and IBD. Elevated
levels of HMGB1 have been detected in inflamed human intestinal tissues and in
feces of IBD patients and mouse models of colitis. Neutralizing HMGB1 activity by
administration of anti-HMGB1 antibodies or HMGB1-specific antagonist improves
clinical outcomes in animal models of colitis. Since HMGB1 binds to DNA with high
affinity, here we developed a novel strategy to sequester HMGB1 using DNA
immobilized on sepharose beads. Screening of DNA-bead constructs revealed that B2
beads, one linear form of DNA conjugated beads, bind HMGB1 with high affinity,
capture HMGB1 ex vivo from endotoxin-stimulated RAW 264.7 cell supernatant and
from feces of mice with colitis. Oral administration of B2 DNA beads
significantly improved body weight, reduced colon injury, and suppressed colonic
and circulating cytokine levels in mice with spontaneous colitis (IL-10 knockout)
and with dextran sulfate sodium-induced colitis. Thus, DNA beads reduce
inflammation by sequestering HMGB1 and may have therapeutic potential for the
treatment of IBD.
PMID- 25127034
TI - Estrogen receptor-alpha36 is involved in pterostilbene-induced apoptosis and anti
proliferation in in vitro and in vivo breast cancer.
AB - Pterostilbene (trans-3,5-dimethoxy-4'-hudroxystilbene) is an antioxidant
primarily found in blueberries. It also inhibits breast cancer regardless of
conventional estrogen receptor (ER-alpha66) status by inducing both caspase
dependent and caspase-independent apoptosis. However, the pterostilbene-induced
apoptosis rate in ER-alpha66-negative breast cancer cells is much higher than
that in ER-alpha66-positive breast cancer cells. ER-alpha36, a variant of ER
alpha66, is widely expressed in ER-alpha66-negative breast cancer, and its high
expression mediates the resistance of ER-alpha66-positive breast cancer patients
to tamoxifen therapy. The aim of the present study is to determine the
relationship between the antiproliferation activity of pterostilbene and ER
alpha36 expression in breast cancer cells. Methyl-thiazolyl-tetrazolium (MTT)
assay, apoptosis analysis, and an orthotropic xenograft mouse model were used to
examine the effects of pterostilbene on breast cancer cells. The expressions of
ER-alpha36 and caspase 3, the activation of ERK and Akt were also studied through
RT-PCR, western blot analysis, and immunohistochemical (IHC) staining. ER-alpha36
knockdown was found to desensitize ER-alpha66-negative breast cancer cells to
pterostilbene treatment both in vitro and in vivo, and high ER-alpha36 expression
promotes pterostilbene-induced apoptosis in breast cancer cells. Western blot
analysis data indicate that MAPK/ERK and PI3K/Akt signaling in breast cancer
cells with high ER-alpha36 expression are mediated by ER-alpha36, and are
inhibited by pterostilbene. These results suggest that ER-alpha36 is a
therapeutic target in ER-alpha36-positive breast cancer, and pterostilbene is an
inhibitor that targets ER-alpha36 in the personalized therapy against ER-alpha36
positive breast cancer.
PMID- 25127035
TI - Response of various conduit arteries in tachycardia- and volume overload-induced
heart failure.
AB - Although hemodynamics changes occur in heart failure (HF) and generally influence
vascular function, it is not clear whether various HF models will affect the
conduit vessels differentially or whether local hemodynamic forces or systemic
factors are more important determinants of vascular response in HF. Here, we
studied the hemodynamic changes in tachycardia or volume-overload HF swine model
(created by either high rate pacing or distal abdominal aortic-vena cava fistula,
respectively) on carotid, femoral, and renal arteries function and molecular
expression. The ejection fraction was reduced by 50% or 30% in tachycardia or
volume-overload model in four weeks, respectively. The LV end diastolic volume
was increased from 65 +/- 22 to 115 +/- 78 ml in tachycardia and 67 +/- 19 to 148
+/- 68 ml in volume-overload model. Flow reversal was observed in diastolic phase
in carotid artery of both models and femoral artery in volume-overload model. The
endothelial function was also significantly impaired in carotid and renal
arteries of tachycardia and volume-overload animals. The endothelial dysfunction
was observed in femoral artery of volume-overload animals but not tachycardia
animals. The adrenergic receptor-dependent contractility decreased in carotid and
femoral arteries of tachycardia animals. The protein expressions of NADPH oxidase
subunits increased in the three arteries and both animal models while expression
of MnSOD decreased in carotid artery of tachycardia and volume-overload model. In
conclusion, different HF models lead to variable arterial hemodynamic changes but
similar vascular and molecular expression changes that reflect the role of both
local hemodynamics as well as systemic changes in HF.
PMID- 25127037
TI - Phenotypic modulation of corpus cavernosum smooth muscle cells in a rat model of
cavernous neurectomy.
AB - BACKGROUND: Patients undergoing radical prostatectomy (RP) are at high risk for
erectile dysfunction (ED) due to potential cavernous nerve (CN) damage during
surgery. Penile hypoxia after RP is thought to significantly contribute to ED
pathogenesis. AIM: We previously showed that corpora cavernosum smooth muscle
cells (CCSMCs) undergo phenotypic modulation under hypoxic conditions in vitro.
Here, we studied such changes in an in vivo post-RP ED model by investigating
CCSMCs in bilateral cavernous neurectomy (BCN) rats. METHODS: Sprague-Dawley rats
underwent sham (n = 12) or BCN (n = 12) surgery. After 12 weeks, they were
injected with apomorphine to determine erectile function. The penile tissues were
harvested and assessed for fibrosis using Masson trichrome staining and for
molecular markers of phenotypic modulation using immunohistochemistry and western
blotting. CCSMC morphological structure was evaluated by hematoxylin-eosin (H&E)
staining and transmission electron microscopy (TEM). RESULTS: Erectile function
was significantly lower in BCN rats than in sham rats. BCN increased hypoxia
inducible factor-1alpha and collagen protein expression in corpora cavernous
tissue. H&E staining and TEM showed that CCSMCs in BCN rats underwent hypertrophy
and showed rough endoplasmic reticulum formation. The expression of CCSMC
phenotypic markers, such as smooth muscle alpha-actin, smooth muscle myosin heavy
chain, and desmin, was markedly lower, whereas vimentin protein expression was
significantly higher in BCN rats than in control rats. CONCLUSIONS: CCSMCs
undergo phenotype modulation in rats with cavernous neurectomy. The results have
unveiled physiological transformations that occur at the cellular and molecular
levels and have helped characterize CN injury-induced ED.
PMID- 25127038
TI - Enhanced biocatalytic esterification with lipase-immobilized chitosan/graphene
oxide beads.
AB - In this work, lipase from Candida rugosa was immobilized onto chitosan/graphene
oxide beads. This was to provide an enzyme-immobilizing carrier with excellent
enzyme immobilization activity for an enzyme group requiring hydrophilicity on
the immobilizing carrier. In addition, this work involved a process for the
preparation of an enzymatically active product insoluble in a reaction medium
consisting of lauric acid and oleyl alcohol as reactants and hexane as a solvent.
This product enabled the stability of the enzyme under the working conditions and
allowed the enzyme to be readily isolated from the support. In particular, this
meant that an enzymatic reaction could be stopped by the simple mechanical
separation of the "insoluble" enzyme from the reaction medium. Chitosan was
incorporated with graphene oxide because the latter was able to enhance the
physical strength of the chitosan beads by its superior mechanical integrity and
low thermal conductivity. The X-ray diffraction pattern showed that the graphene
oxide was successfully embedded within the structure of the chitosan. Further,
the lipase incorporation on the beads was confirmed by a thermo-gravimetric
analysis. The lipase immobilization on the beads involved the functionalization
with coupling agents, N-hydroxysulfosuccinimide sodium (NHS) and 1-ethyl-(3
dimethylaminopropyl) carbodiimide (EDC), and it possessed a high enzyme activity
of 64 U. The overall esterification conversion of the prepared product was 78% at
60 degrees C, and it attained conversions of 98% and 88% with commercially
available lipozyme and novozyme, respectively, under similar experimental
conditions.
PMID- 25127039
TI - IGFBP3 methylation is a novel diagnostic and predictive biomarker in colorectal
cancer.
AB - BACKGROUND AND AIM: Aberrant hypermethylation of cancer-related genes has emerged
as a promising strategy for the development of diagnostic, prognostic and
predictive biomarkers in human cancer, including colorectal cancer (CRC). The aim
of this study was to perform a systematic and comprehensive analysis of a panel
of CRC-specific genes as potential diagnostic, prognostic and predictive
biomarkers in a large, population-based CRC cohort. PATIENTS AND METHODS:
Methylation status of the SEPT9, TWIST1, IGFBP3, GAS7, ALX4 and miR137 genes was
studied by quantitative bisulfite pyrosequencing in a population-based cohort of
425 CRC patients. RESULTS: Methylation levels of all genes analyzed were
significantly higher in tumor tissues compared to normal mucosa (p<0.0001);
however, cancer-associated hypermethylation was most frequently observed for
miR137 (86.7%) and IGFBP3 (83%) in CRC patients. Methylation analysis using the
combination of these two genes demonstrated greatest accuracy for the
identification of colonic tumors (sensitivity 95.5%; specificity 90.5%). Low
levels of IGFBP3 promoter methylation emerged as an independent risk factor for
predicting poor disease free survival in stage II and III CRC patients (HR =
0.49, 95% CI: 0.28-0.85, p = 0.01). Our results also suggest that stage II & III
CRC patients with high levels of IGFBP3 methylation do not benefit from adjuvant
5FU-based chemotherapy. CONCLUSION: By analyzing a large, population-based CRC
cohort, we demonstrate the potential clinical significance of miR137 and IGFBP3
hypermethylation as promising diagnostic biomarkers in CRC. Our data also
revealed that IGFBP3 hypermethylation may serve as an independent prognostic and
predictive biomarker in stage II and III CRC patients.
PMID- 25127042
TI - Determination of critical nitrogen dilution curve based on stem dry matter in
rice.
AB - Plant analysis is a very promising diagnostic tool for assessment of crop
nitrogen (N) requirements in perspectives of cost effective and environment
friendly agriculture. Diagnosing N nutritional status of rice crop through plant
analysis will give insights into optimizing N requirements of future crops. The
present study was aimed to develop a new methodology for determining the critical
nitrogen (Nc) dilution curve based on stem dry matter (SDM) and to assess its
suitability to estimate the level of N nutrition for rice (Oryza sativa L.) in
east China. Three field experiments with varied N rates (0-360 kg N ha(-1)) using
three Japonica rice hybrids, Lingxiangyou-18, Wuxiangjing-14 and Wuyunjing were
conducted in Jiangsu province of east China. SDM and stem N concentration (SNC)
were determined during vegetative stage for growth analysis. A Nc dilution curve
based on SDM was described by the equation (Nc = 2.17W(-0.27) with W being SDM in
t ha(-1)), when SDM ranged from 0.88 to 7.94 t ha(-1). However, for SDM < 0.88 t
ha(-1), the constant critical value Nc = 1.76% SDM was applied. The curve was
dually validated for N-limiting and non-N-limiting growth conditions. The N
nutrition index (NNI) and accumulated N deficit (Nand) of stem ranged from 0.57
to 1.06 and 51.1 to -7.07 kg N ha(-1), respectively, during key growth stages
under varied N rates in 2010 and 2011. The values of DeltaN derived from either
NNI or Nand could be used as references for N dressing management during rice
growth. Our results demonstrated that the present curve well differentiated the
conditions of limiting and non-limiting N nutrition in rice crop. The SDM based
Nc dilution curve can be adopted as an alternate and novel approach for
evaluating plant N status to support N fertilization decision during the
vegetative growth of Japonica rice in east China.
PMID- 25127040
TI - Toll-like receptor-3 is dispensable for the innate microRNA response to West Nile
virus (WNV).
AB - The innate immune response to West Nile virus (WNV) infection involves
recognition through toll-like receptors (TLRs) and RIG-I-like receptors (RLRs),
leading to establishment of an antiviral state. MiRNAs (miRNAs) have been shown
to be reliable biomarkers of TLR activation. Here, we sought to evaluate the
contribution of TLR3 and miRNAs to the host response to WNV infection. We first
analyzed HEK293-NULL and HEK293-TLR3 cells for changes in the innate immune
response to infection. The presence of TLR3 did not seem to affect WNV load,
infectivity or phosphorylation of IRF3. Analysis of experimentally validated
NFkappaB-responsive genes revealed a WNV-induced signature largely independent of
TLR3. Since miRNAs are involved in viral pathogenesis and the innate response to
infection, we sought to identify changes in miRNA expression upon infection in
the presence or absence of TLR3. MiRNA profiling revealed 70 miRNAs induced
following WNV infection in a TLR3-independent manner. Further analysis of
predicted gene targets of WNV signature miRNAs revealed genes highly associated
with pathways regulating cell death, viral pathogenesis and immune cell
trafficking.
PMID- 25127044
TI - Exploiting monitoring data in environmental exposure modelling and risk
assessment of pharmaceuticals.
AB - In order to establish the environmental impact of an active pharmaceutical
ingredient (API), good information on the level of exposure in surface waters is
needed. Exposure concentrations are typically estimated using information on the
usage of an API as well as removal rates in the patient, the wastewater system
and in surface waters. These input data are often highly variable and difficult
to obtain, so model estimates often do not agree with measurements made in the
field. In this paper we present an approach which uses inverse modelling to
estimate overall removal rates of pharmaceuticals at the catchment scale using a
hydrological model as well as prescription and monitoring data for a few
representative sites for a country or region. These overall removal rates are
then used to model exposure across the broader landscape. Evaluation of this
approach for APIs in surface waters across England and Wales showed good
agreement between modelled exposure distributions and available monitoring data.
The use of the approach, alongside estimates of predicted no-effect
concentrations for the 12 study compounds, to assess risk of the APIs across the
UK landscape, indicated that, for most of the compounds, risks to aquatic life
were low. However, ibuprofen was predicted to pose an unacceptable risk in 49.5%
of the river reaches studied. For diclofenac, predicted exposure concentrations
were also compared to the Environmental Quality Standard previously proposed by
the European Commission and 4.5% of river reaches were predicted to exceed this
concentration. While the current study focused on pharmaceuticals, the approach
could also be valuable in assessing the risks of other 'down the drain' chemicals
and could help inform our understanding of the important dissipation processes
for pharmaceuticals in the pathway from the patient to ecological receptors.
PMID- 25127041
TI - SPO24 is a transcriptionally dynamic, small ORF-encoding locus required for
efficient sporulation in Saccharomyces cerevisiae.
AB - In Saccharomyces cerevisiae, meiosis and sporulation are highly regulated
responses that are driven in part by changes in RNA expression. Alternative mRNA
forms with extended 5' UTRs are atypical in S. cerevisiae, and 5' extensions with
upstream open reading frames (uORFs) are even more unusual. Here we characterize
the gene YPR036W-A, now renamed SPO24, which encodes a very small (67-amino-acid)
protein. This gene gives rise to two mRNA forms: a shorter form throughout
meiosis and a longer, 5'-extended form in mid-late meiosis. The latter form
includes a uORF for a 14-amino-acid peptide (Spo24u14). Deletion of the
downstream ORF (dORF) leads to sporulation defects and the appearance of
pseudohyphae-like projections. Experiments with luciferase reporters indicate
that the uORF does not downregulate dORF translation. The protein encoded by the
dORF (Spo24d67) localizes to the prospore membrane and is differentially
phosphorylated during meiosis. Transcription of the 5'-extended mRNA in mid
meiosis depends upon the presence of two middle sporulation elements (MSEs).
Removal of the MSEs severely inhibits the mid-meiotic appearance of the 5'
extended mRNA and limits the ability of plasmid-borne SPO24 to rescue the
sporulation defect of a spo24Delta mutant, suggesting that the 5'-extended mRNA
is functionally important. These results reveal Spo24d67 as a sporulation-related
factor that is encoded by a transcriptionally dynamic, uORF-containing locus.
PMID- 25127045
TI - Diagnostic and therapeutic challenges.
PMID- 25127043
TI - Antibiotic resistance genes in bacterial and bacteriophage fractions of Tunisian
and Spanish wastewaters as markers to compare the antibiotic resistance patterns
in each population.
AB - The emergence and increased prevalence of antibiotic resistance genes (ARGs) in
the environment may pose a serious global health concern. This study evaluates
the abundance of several ARGs in bacterial and bacteriophage DNA via real-time
qPCR in samples from five different sampling points in Tunisia; three wastewater
treatment plants (WWTP 1, 2 and 3) and wastewater from two abattoirs slaughtering
different animals. Results are compared with those obtained in the Barcelona
area, in northeast Spain. Eight ARGs were quantified by qPCR from total and phage
DNA fraction from the samples. Three beta-lactamases (bla(TEM), bla(CTX-M)
cluster 1 and bla(CTX-M) cluster 9), two quinolone resistance genes (qnrA and
qnrS), the mecA gene that confers resistance to methicillin in Staphylococcus
aureus, the emerging armA gene, conferring resistance to aminoglycosides and
sul1, the most extended gene conferring resistance to sulfonamides, were
evaluated. Sul1 and bla(TEM) were the most prevalent ARGs detected at all five
Tunisian sampling points, similarly with the observations in Barcelona. bla(CTX-M
9) was more prevalent than bla(CTX-M-1) both in bacterial and DNA within phage
particles in all samples analysed. mecA and armA were almost absent in Tunisian
waters from human or animal origin in contrast with Barcelona that showed a
medium prevalence. qnrA was more prevalent than qnrS in bacterial and phage DNA
from all sampling points. In conclusion, our study shows that ARGs are found in
the bacterial and is reflected in the phage DNA fraction of human and animal
wastewaters. The densities of each ARGs vary depending on the ARGs shed by each
population and is determined by the characteristics of each area. Thus, the
evaluation of ARGs in wastewaters seems to be suitable as marker reflecting the
antibiotic resistance patterns of a population.
PMID- 25127046
TI - Spectral domain optical coherence tomography findings in long-term silicone oil
related visual loss.
AB - PURPOSE: To investigate spectral domain optical coherence tomography findings in
long-term silicone oil-related visual loss. METHODS: Four symptomatic patients
were reviewed 4 years to 9 years after vitrectomy with silicone oil tamponade for
macula-on retinal detachment. Three lost vision with oil in situ, with one at the
time of oil removal. Eleven control eyes with good vision were included. Patients
underwent assessment of best-corrected visual acuity, contrast sensitivity,
Farnsworth-Munsell 100 Hue testing, static perimetry, and spectral domain optical
coherence tomography imaging of the macula and disk. RESULTS: Long-term best
corrected visual acuity was significantly reduced in affected eyes (range, 0.44
1.02), as was contrast sensitivity (0.75-1.35) and color discrimination
(Farnsworth-Munsell-100 Hue score, 151-390). Static perimetry showed a central
scotoma in all affected eyes. Optical coherence tomography revealed microcystic
macular changes in the inner nuclear layer of all affected eyes associated with
severe loss of the papillofoveal retinal nerve fiber layer. In one patient,
serial optical coherence tomography images showed development of microcystic
macular changes 18 months after oil removal. Control eyes lacked these features,
except two asymptomatic eyes that showed microcystic changes on optical coherence
tomography with a corresponding paracentral scotoma. CONCLUSION: We have
demonstrated microcystic macular changes in the inner nuclear layer of affected
eyes, as well as focal severe loss of the papillofoveal projection. These changes
share significant morphologic features reported in multiple sclerosis-associated
optic neuritis and Leber hereditary optic neuropathy.
PMID- 25127047
TI - Retinal detachment associated with ocular toxoplasmosis.
AB - PURPOSE: To assess the frequency of retinal detachment (RD) and associated
clinical features in ocular toxoplasmosis. METHODS: A review of the medical
records of patients diagnosed with ocular toxoplasmosis and follow-up of 6 months
or more was conducted. All patients were seen at the Casey Eye Institute at the
Oregon Health & Science University over a 9-year period (2003-2012). Demographic
data, presence of RD and/or vitritis, and treatments were reviewed. Main outcome
measures were the rate of RD in ocular toxoplasmosis, degree of vision loss, and
final anatomical status of the retina. Disease- and treatment-related factors
associated with poor visual outcome were also analyzed. RESULTS: Thirty-five eyes
of 28 patients with ocular toxoplasmosis and sufficient follow-up were studied.
Median age of patients was 40 years (range, 7-93 years). Median follow-up time
was 22.5 months (range, 6-96 months). Four of thirty-five eyes (11.4%) developed
RD with a frequency of 0.06 RD events per patient-year of follow-up in this
sample in a single center. Of four patients with RD, three underwent pars plana
vitrectomy and one underwent laser retinopexy. Two of the 4 patients had
recurrent RD requiring scleral buckle. At final follow-up, all patients who
underwent surgical repair had attached retinas; however, 3 of 4 patients had
severe vision loss (20/200 or worse). CONCLUSION: Retinal detachment occurred in
11% of eyes in this study that led to severe vision loss despite successful RD
repair.
PMID- 25127048
TI - A 10-year review of open-globe trauma in elderly patients at an urban hospital.
AB - BACKGROUND: To describe the demographics, characteristics, and outcomes of open
globe injuries (OGIs) in elderly patients. METHODS: Retrospective chart review.
RESULTS: Ninety cases (26 men) were identified. The average age was 80 years
(range, 65-96 years). The types of OGIs included rupture (83.3%) and penetrating
(16.7%) injuries. The causes of trauma were falls (64.4%), accidents (20%), motor
vehicle accidents (5.5%), and assault (3.33%). Types of lacerations included
corneal (44.4%), corneoscleral (26.7%), and scleral (28.9%). Forty-six cases were
OGIs because of dehiscence of previous ocular surgical wound. Ten eyes had
concurrent orbital fractures. Approximately 81.1% of cases underwent primary OGI
repair within 24 hours of injury, and all cases underwent primary OGI repair
within 24 hours of admission. The average visual acuity at presentation was
20/4,375 (SD, 0.64). Although 22 patients presented with no light perception,
only 10 remained no light perception after OGI repair. Complications at
presentation included uveal prolapse (70%), hemorrhagic choroidal detachment
(37.8%), vitreous hemorrhage (51.1%), retinal detachment (20%), and afferent
pupillary defect (42.2%). Three patients (3.33%) underwent primary pars plana
vitrectomy for retinal detachment and vitreous hemorrhage. Three patients
developed endophthalmitis. Overall, retinal attachment was achieved in all eyes
that underwent primary pars plana vitrectomy. Primary enucleations were performed
in 4 cases (4.44%) for nonsalvageable no light perception eyes. CONCLUSION: The
visual prognosis of OGIs in the elderly population is poor; only 14.4% achieved
20/200 or better visual acuity. Precautionary measures should be taken to prevent
OGIs in the elderly population.
PMID- 25127050
TI - Low-intensity/high-density subthreshold microPulse diode laser for chronic
central serous chorioretinopathy.
AB - PURPOSE: To evaluate the visual outcomes and macular thickness change in patients
with symptomatic chronic central serous chorioretinopathy after treatment with a
subthreshold MicroPulse diode laser. METHODS: In this retrospective,
interventional case series, 10 patients were treated with the subthreshold 810-nm
diode MicroPulse laser. Selected patients had symptomatic disease that may or may
not have involved the foveal center. The MicroPulse laser was applied to the
areas of leakage seen on fluorescein angiogram, over the areas of clinical
neurosensory detachment, and/or pigment epithelial detachments. Pretreatment and
posttreatment vision, change in maximum macular thickness, number of treatment
sessions, and number of laser spot applications were recorded. Patients were
excluded if they did not attend follow-up, had other confounding macular
diseases, were using steroid medications, or application of another treatment
modality had been used (i.e., photodynamic therapy or anti-vascular endothelial
growth factor medication). RESULTS: Ten patients met the inclusion criteria, with
1 patient treated in both eyes. Three patients were excluded for lack of follow
up, one for the use of systemic steroids, and one for treatment with anti
vascular endothelial growth factor injection. Maximum macular thickness decreased
after subthreshold MicroPulse laser treatment between 20 MUm and 338 MUm (mean =
97 MUm decrease, P = 0.0046) in 11 treated eyes. CONCLUSION: Subthreshold diode
MicroPulse laser is a potential treatment option for patients with symptomatic
chronic central serous chorioretinopathy.
PMID- 25127049
TI - Obstructive sleep apnea and central serous chorioretinopathy.
AB - PURPOSE: The purpose of this study was to determine if there is an association
between obstructive sleep apnea (OSA) and central serous chorioretinopathy
(CSCR). METHODS: Patients with CSCR without a history of steroid use or secondary
retinal disease were matched based on age/gender/body mass index with control
patients and administered the Berlin Questionnaire to assess for OSA risk.
Patients were scored "OSA+" if they were at "high risk" on the Berlin
Questionnaire or reported a previous OSA diagnosis. Rates of OSA+ were compared
between the 2 groups, odds ratio and its 95% confidence interval was calculated
using exact conditional logistic regression. RESULTS: Forty-eight qualifying
patients with CSCR were identified. There were no statistically significant
differences between the CSCR and control groups by age (mean = 55 years), gender
(79% male), body mass index (mean = 28.2), history of diabetes, or hypertension.
Within the CSCR group, 22 patients (45.8%) were OSA+ versus 21 control patients
(43.8%) (difference = 2.1%; 95% confidence interval, -18.2% to 22.2%; exact odds
ratio = 1.08, 95% confidence interval, 0.47-2.49; P = 1.00). CONCLUSION: When
compared with matched controls, patients with CSCR did not have statistically
significant higher rates of OSA risk or previous diagnosis. This finding
contrasts with previous work showing a strong association between the diseases.
The divergence is likely due to our matching controls for body mass index, a
significant risk factor for OSA.
PMID- 25127051
TI - Re: Multimodal imaging findings in retinal deep capillary ischemia.
PMID- 25127052
TI - Re: Subretinal hyperreflective exudation associated with neovascular age-related
macular degeneration.
PMID- 25127053
TI - Reply: To PMID 24240565.
PMID- 25127054
TI - Reply: To PMID 24695062.
PMID- 25127055
TI - Priming and activation of NADPH oxidases in plants and animals.
AB - In mammals, engagement of Toll-like receptors by microbe-associated molecular
patterns enhances the responsiveness of NADPH oxidases. Two recent papers report
a similar 'priming' mechanism for the plant oxidase RbohD. Despite lacking
structural homology, the functional parallels between plants and animals reveal
that a common regulatory logic arose by convergent evolution.
PMID- 25127058
TI - Myeloma genetics and genomics: practice implications and future directions.
AB - Multiple myeloma (MM) is a heterogeneous, clonal disorder of the plasma cells
originating from the B-cell line. The diagnosis and monitoring of MM requires
routine measurement of biomarkers such as serum protein electrophoresis, urine
protein electrophoresis, serum free light chains, among others. Prognostic models
such as the Durie-Salmon staging system and International Staging System are
available and account for the disease burden. Advanced biomarker and genetic
testing includes cytogenetics, fluorescent in situ hybridization, and gene
expression profiling to estimate the aggressiveness of the disease and
personalize the patient's treatment. Future goals of therapy will be to achieve
minimal residual disease (MRD), which incorporates biomarkers and genomic data.
MRD testing might provide a better estimate of the depth of response to therapy
and overall survival. A robust genomic program of research is still needed to
provide additional information for the best MM care practices and to gain new
strategies to treat the disease, in particular, in the relapsed and/or refractory
setting.
PMID- 25127059
TI - Large myocardial infarction with myocardium calcium deposits associated with
reperfusion injury.
AB - The clinical and autopsy findings of a 66-year-old man with myocardial infarction
complicated by reperfusion injury are described, highlighting the presence of
large myocardium calcium deposits.
PMID- 25127056
TI - Notch and hippo converge on Cdx2 to specify the trophectoderm lineage in the
mouse blastocyst.
AB - The first lineage choice in mammalian embryogenesis is that between the
trophectoderm, which gives rise to the trophoblast of the placenta, and the inner
cell mass, from which is derived the embryo proper and the yolk sac. The
establishment of these lineages is preceded by the inside-versus-outside
positioning of cells in the early embryo and stochastic expression of key
transcription factors, which is then resolved into lineage-restricted expression.
The regulatory inputs that drive this restriction and how they relate to cell
position are largely unknown. Here, we show an unsuspected role of Notch
signaling in regulating trophectoderm-specific expression of Cdx2 in cooperation
with TEAD4. Notch activity is restricted to outer cells and is able to influence
positional allocation of blastomeres, mediating preferential localization to the
trophectoderm. Our results show that multiple signaling inputs at preimplantation
stages specify the first embryonic lineages.
PMID- 25127057
TI - TRIM proteins regulate autophagy and can target autophagic substrates by direct
recognition.
AB - Autophagy, a homeostatic process whereby eukaryotic cells target cytoplasmic
cargo for degradation, plays a broad role in health and disease states. Here we
screened the TRIM family for roles in autophagy and found that half of TRIMs
modulated autophagy. In mechanistic studies, we show that TRIMs associate with
autophagy factors and act as platforms assembling ULK1 and Beclin 1 in their
activated states. Furthermore, TRIM5alpha acts as a selective autophagy receptor.
Based on direct sequence-specific recognition, TRIM5alpha delivered its cognate
cytosolic target, a viral capsid protein, for autophagic degradation. Thus, our
study establishes that TRIMs can function both as regulators of autophagy and as
autophagic cargo receptors, and reveals a basis for selective autophagy in
mammalian cells.
PMID- 25127060
TI - Youth, friendship, and gaming: a network perspective.
AB - With digital games being part of the leisure of a multitude of young people, it
is important to understand to what extent gaming-related practices such as
talking about games or playing games together are associated with the quality of
friendship relations with players and nonplayers. Based on 100 friendship
networks, this study explored to what extent those practices permeated the
everyday life of youngsters and whether they could be considered as a part of
doing friendship. Results indicated that gaming as a conversational topic was
widespread within and between networks. Furthermore, regardless of gender, this
was significantly associated with friendship quality in almost all of the
networks. When considering playing games together, a somewhat different picture
emerged. In contrast to conversational practices, playing together was less
widespread. Moreover, both the occurrence and the effect of co-play and
friendship quality was gendered. The findings of this study show that a focus on
gaming-related practices yields a fruitful starting point when considering the
role of digital games in a social context that is not limited to people playing
(online) games. Furthermore, they also feed into the ongoing debate of possible
effects of digital games in that it shows that the way in which games influence
the lives of young people goes beyond a direct effects approach.
PMID- 25127061
TI - [Latent chronic eosinophilic pneumonia in a patient previously treated with
immunomodulators].
PMID- 25127063
TI - Prognostic factors of long-term outcome in cases of severe traumatic brain
injury.
AB - INTRODUCTION: The purpose of this monocentric study was to assess the long-term
outcome of a group of severe traumatic brain-injured patients and explore the
prognostic values of some clinical and paraclinical parameters available at the
initial stage. METHODOLOGY: The patients included were victims of severe
traumatic brain injuries in 2007 or 2008. A standardized assessment was performed
for each patient including clinical, radiological, and electrophysiological data
collected at the initial stage, The outcomes were assessed at least 2 years after
injury. Depending on the patients' availability and ability to communicate, the
assessments included measures of dependency for activities of daily living (ADL),
cognitive functions, behaviour, mood, and quality of life. RESULTS: Eighteen
patients were included, of whom ten were autonomous for ADL at the time of
assessment. Memory complaints, attentional deficits, anxiety, and irritability
were the main long-term impairments observed. A correlation analysis showed
significant correlations between the dependency level (as rated by the Functional
Independence Measure) and each of length of coma, length of the post-traumatic
amnesia, and the N100 auditory evoked potentials. DISCUSSION: These results
confirm the uniqueness of each patient regarding the long-term consequences of a
traumatic brain injury and the multi-determined nature of each prognosis.
PMID- 25127062
TI - HIV-1 transgenic rats display alterations in immunophenotype and cellular
responses associated with aging.
AB - Advances in anti-retroviral therapy over the last two decades have allowed life
expectancy in patients infected with the human immunodeficiency virus to approach
that of the general population. The process of aging in mammalian species,
including rats, results in immune response changes, alterations in immunological
phenotypes, and ultimately increased susceptibility to many infectious diseases.
In order to investigate the immunological pathologies associated with chronic HIV
1 disease, particularly in aging individuals, the HIV-1 transgenic (HIV-1Tg) rat
model was utilized. HIV-1Tg rats were challenged with lipopolysaccharide (LPS) to
determine immunological alterations during the aging process. LPS is known to
cause an imbalance in cytokine and chemokine release, and provides a method to
identify changes in immune responses to bacterial infection in an HIV animal
model. An immune profile and accompanying cellular consequences as well as
changes in inflammatory cytokine and chemokine release related to age and
genotype were assessed in HIV-1Tg rats. The percentage of T cells decreased with
age, particularly T cytotoxic cells, whereas T helper cells increased with age.
Neutrophils and monocytes increased in HIV-1Tg rats during maturation compared to
age-matched F344 control rats. Aging HIV-1Tg rats displayed a significant
increase in the pro-inflammatory cytokines, IL-6 and TNF-alpha, along with an
increase in the chemokine, KC/GRO, in comparison to age-matched controls. Our
data indicate that immunophenotype and immune responses can change during aging
in HIV-positive individuals. This information could be important in determining
the most beneficial age-dependent therapeutic treatment for HIV patients.
PMID- 25127065
TI - Partial purification and characterization of chromate reductase of a novel
Ochrobactrum sp. strain Cr-B4.
AB - Hexavalent chromium contamination is a serious problem due to its high toxicity
and carcinogenic effects on the biological systems. The enzymatic reduction of
toxic Cr(VI) to the less toxic Cr(III) is an efficient technology for
detoxification of Cr(VI)-contaminated industrial effluents. In this regard, a
chromate reductase enzyme from a novel Ochrobactrum sp. strain Cr-B4, having the
ability to detoxify Cr(VI) contaminated sites, has been partially purified and
characterized. The molecular mass of this chromate reductase was found to be
31.53 kD, with a specific activity 14.26 U/mg without any addition of electron
donors. The temperature and pH optima for chromate reductase activity were 40
degrees C and 8.0, respectively. The activation energy (Ea) for the chromate
reductase was found to be 34.7 kJ/mol up to 40 degrees C and the activation
energy for its deactivation (Ed) was found to be 79.6 kJ/mol over a temperature
range of 50-80 degrees C. The frequency factor for activation of chromate
reductase was found to be 566.79 s(-1), and for deactivation of chromate
reductase it was found to be 265.66 * 10(3) s(-1). The reductase activity of this
enzyme was affected by the presence of various heavy metals and complexing
agents, some of which (ethylenediamine tetraacetic acid [EDTA], mercaptoethanol,
NaN3, Pb(2+), Ni(2+), Zn(2+), and Cd(2+)) inhibited the enzyme activity, while
metals like Cu(2+) and Fe(3+) significantly enhanced the reductase activity. The
enzyme followed Michaelis-Menten kinetics with Km of 104.29 uM and a Vmax of 4.64
uM/min/mg.
PMID- 25127064
TI - Motor function levels and pelvic parameters in walking or ambulating children
with cerebral palsy.
AB - BACKGROUND: In children with cerebral palsy, spinal equilibrium and pelvic
strategies may vary according to the functional status. OBJECTIVES: To study the
relationship between motor function and pelvic and spinal parameters in a
population of children and adolescents with cerebral palsy (rated from level I to
level IV on Gross Motor Function Classification System [GMFCS]). A sagittal X-ray
of the spine in the standing position was analyzed with Optispine((r)) software.
RESULTS: The study population comprised 114 children and adolescents (mean
[range] age: 12.35 [4-17]). For the study population as a whole, there were
significant overall correlations between the GMFCS level on one hand and pelvic
incidence and pelvic tilt (PT) on the other (P=0.013 and 0.021, respectively).
DISCUSSION: Pelvic parameters vary according to the GMFCS level but do not appear
to affect spinal curvature. The sacrum is positioned in front of the head of the
femur (i.e. negative PT) in GMFCS level I and progressively moves backwards (i.e.
positive PT) in GMFCS levels II, III and IV.
PMID- 25127066
TI - First-order kinetics of landfill leachate treatment in a pilot-scale anaerobic
sequence batch biofilm reactor.
AB - This paper reports the kinetics evaluation of landfill leachate anaerobic
treatment in a pilot-scale Anaerobic Sequence Batch Biofilm Reactor (AnSBBR). The
experiment was carried out at room temperature (23.8 +/- 2.1 degrees C) in the
landfill area in Sao Carlos-SP, Brazil. Biomass from the bottom of a local
landfill leachate stabilization pond was used as inoculum. After acclimated and
utilizing leachate directly from the landfill, the AnSBBR presented efficiency
over 70%, in terms of COD removal, with influent COD ranging from 4825 mg L(-1)
to 12,330 mg L(-1). To evaluate the kinetics of landfill leachate treatment,
temporal profiles of CODFilt. concentration were performed and a first-order
kinetics model was adjusted for substrate consumption, obtaining an average k1 =
4.40 * 10(-5) L mgTVS(-1) d(-1), corrected to 25 degrees C. Considering the
temperature variations, a temperature-activity coefficient theta = 1.07 was
obtained. Statistical "Randomness" and "F" tests were used to successfully
validate the model considered. Thus, the results demonstrate that the first-order
kinetic model is adequate to model the anaerobic treatment of the landfill
leachate in the AnSBBR.
PMID- 25127067
TI - Delayed vocal fold paralysis after continuous interscalene level brachial plexus
block with catheter placement: a case report.
AB - We report an incident of delayed onset of true vocal fold paralysis with
continuous interscalene brachial plexus block. A 51 year old woman underwent left
shoulder manipulation and lysis of adhesions with fluoroscopy and general
anesthesia. An interscalene brachial plexus block was performed and a catheter
with a continuous infusion pump was placed for postoperative pain control.
Following hospital discharge, approximately 8 hours after the initial catheter
bolus the patient developed hoarseness, dysphagia, and dyspnea, secondary to left
vocal fold palsy. The patient was admitted for observation and the catheter was
discontinued with no intubation required. By the next morning, the patient's
dysphagia and dyspnea had resolved and her hoarseness improved.
PMID- 25127068
TI - Semicarbazide - from state-of-the-art analytical methods and exposure to
toxicity: a review.
AB - This review assesses the state of the art concerning semicarbazide (SEM).
Originally, SEM was primarily detected as a nitrofurazone veterinary metabolite,
but over time scientists gradually found that azodicarbonamide in sealed cans and
flour could also lead to the generation of SEM. This discovery makes the study of
SEM particularly interesting. At present, an increasing number of researchers are
investigating the toxicity of SEM and developing more and better analytical
methods for the determination of SEM. In recent years, many researchers have
focused on exposure from different foods, the public awareness of hazards and
analytical detection methods for SEM in different foods. Although there have been
significant achievements, these results have not been summarised in a review. The
exposure from different foods, toxicity and methods of detection for SEM are
comprehensively reviewed here. This review will provide not only others with a
better understanding of SEM but also background information to facilitate future
research.
PMID- 25127070
TI - Transparent and flexible supercapacitors with single walled carbon nanotube thin
film electrodes.
AB - We describe a simple process for the fabrication of transparent and flexible,
solid-state supercapacitors. Symmetric electrodes made up of binder-free single
walled carbon nanotube (SWCNT) thin films were deposited onto
polydimethylsiloxane substrates by vacuum filtration followed by a stamping
method, and solid-state supercapacitor devices were assembled using a gel
electrolyte. An optical transmittance of 82% was found for 0.02 mg of SWCNTs, and
a specific capacitance of 22.2 F/g was obtained. The power density can reach to
41.5 kW . kg(-1) and shows good capacity retention (94%) upon cycling over 500
times. Fabricated supercapacitors will be relevant for the realization of
transparent and flexible devices with energy storage capabilities, displays and
touch screens in particular.
PMID- 25127069
TI - Comparative angioprotective effects of magnesium compounds.
AB - Magnesium (Mg) deficiency is implicated in the development of numerous disorders
of the cardiovascular system. Moreover, the data regarding the efficacy of
different magnesium compounds in the correction of impaired functions due to low
magnesium intake are often fragmentary and inconsistent. The aim of this study
was to compare the effects of the most bioavailable Mg compounds (Mg l-aspartate,
Mg N-acetyltaurate, Mg chloride, Mg sulphate and Mg oxybutyrate) on systemic
inflammation and endothelial dysfunction in rats fed a low Mg diet for 74 days. A
low Mg diet decreased the Mg concentration in the plasma and erythrocytes, which
was accompanied by a reduced concentration of eNOs and increased levels of
endothelin-1 level in the serum and impaired endothelium-dependent
vasodilatation. These effects increased the concentration of proinflammatory
molecules, such as VCAM-1, TNF-alpha, IL-6 and CRP, indicating the development of
systemic inflammation and endothelial dysfunction. The increased total NO level,
which estimated from the sum of the nitrate and nitrite concentrations in the
serum, may also be considered to be a proinflammatory marker. Two weeks of Mg
supplementation partially or fully normalised the ability of the vascular wall to
effect adequate endothelium-dependent vasodilatation and reversed the levels of
most endothelial dysfunction and inflammatory markers (except CRP) to the mean
values of the control group. Mg sulphate had the smallest effect on the
endothelin-1, TNF-alpha and VCAM-1 levels. Mg N-acetyltaurate was significantly
more effective in restoring the level of eNOS compared to all other studied
compounds, except for Mg oxybutyrate. Taken together, the present findings
demonstrate that all Mg compounds equally alleviate endothelial dysfunction and
inflammation caused by Mg deficiency. Mg sulphate tended to be the least
effective compound.
PMID- 25127072
TI - Historical Mercury releases from commercial products: global environmental
implications.
AB - The intentional use of mercury (Hg) in products and processes ("commercial Hg")
has contributed a large and previously unquantified anthropogenic source of Hg to
the global environment over the industrial era, with major implications for Hg
accumulation in environmental reservoirs. We present a global inventory of
commercial Hg uses and releases to the atmosphere, water, soil, and landfills
from 1850 to 2010. Previous inventories of anthropogenic Hg releases have focused
almost exclusively on atmospheric emissions from "byproduct" sectors (e.g.,
fossil fuel combustion). Cumulative anthropogenic atmospheric Hg emissions since
1850 have recently been estimated at 215 Gg (only including commercial Hg
releases from chlor-alkali production, waste incineration, and mining). We find
that other commercial Hg uses and nonatmospheric releases from chlor-alkali and
mining result in an additional 540 Gg of Hg released to the global environment
since 1850 (air: 20%; water: 30%; soil: 30%; landfills: 20%). Some of this
release has been sequestered in landfills and benthic sediments, but 310 Gg
actively cycles among geochemical reservoirs and contributes to elevated present
day environmental Hg concentrations. Commercial Hg use peaked in 1970 and has
declined sharply since. We use our inventory of historical environmental releases
to force a global biogeochemical model that includes new estimates of the global
burial in ocean margin sediments. Accounting for commercial Hg releases improves
model consistency with observed atmospheric concentrations and associated
historical trends.
PMID- 25127071
TI - Complementary and alternative medicine use in infertility: cultural and religious
influences in a multicultural Canadian setting.
AB - OBJECTIVES: To explore the use of complementary and alternative medicine (CAM)
for infertility in a multicultural healthcare setting and to compare Western and
non-Western infertility patients' reasons for using CAM and the meanings they
attribute to CAM use. DESIGN: Qualitative semi-structured interviews using
thematic analysis. SETTINGS/LOCATION: Two infertility clinics in Montreal,
Quebec, Canada. PARTICIPANTS: An ethnoculturally varied sample of 32 heterosexual
infertile couples. RESULTS: CAM used included lifestyle changes (e.g., changing
diet, exercise), alternative medicine (e.g., acupuncture, herbal medicines), and
religious methods (e.g., prayers, religious talismans). Patients expressed three
attitudes toward CAM: desperate hope, casual optimism, and amused skepticism.
PARTICIPANTS' CAM use was consistent with cultural traditions of health and
fertility: Westerners relied primarily on biomedicine and used CAM mainly for
relaxation, whereas non-Westerners' CAM use was often influenced by culture
specific knowledge of health, illness and fertility. CONCLUSIONS: Understanding
patients' CAM use may help clinicians provide culturally sensitive, patient
centered care.
PMID- 25127073
TI - Facilitators and Barriers to Implementing Screening, Brief Intervention, and
Referral to Treatment (SBIRT) in Primary Care in Integrated Health Care Settings.
AB - BACKGROUND: Substance abuse in the United States is a serious public health
concern impacting morbidity and mortality. However, systematic screening and
intervention has not been widely adopted into routine practice by health care
organizations and routine screening and intervention is not currently in place
for primary care at Kaiser Permanente Colorado. Therefore, a formative evaluation
was conducted to explore and enhance implementation of the Substance Abuse and
Mental Health Services Administration (SAMHSA) screening, brief intervention, and
referral to treatment (SBIRT) approach in the organization. METHODS: Key clinical
stakeholders, including internal and family medicine physicians, primary care
nurses, mental health therapists, chemical dependency clinicians, and clinic
based psychologists provided feedback. Two focus groups were also conducted with
patient stakeholders: one in English and one in Spanish. RESULTS: All clinical
stakeholders promoted clinic-based psychologists to conduct brief intervention
and determine referral to treatment as the optimal implementation program.
Inclusion of the patient perspective also highlighted the importance of
considering this perspective in implementation. Both patient groups were
generally supportive of SBIRT, especially the educational value of screening
questions defining healthy drinking limits; however, English-speaking patients
noted privacy concerns and Spanish-speaking patients noted frequently being asked
about drug or alcohol use. Organizationally, systems exist to facilitate drug and
alcohol use screening, intervention, and referral to treatment. However,
physician time, alignment with other priorities, and lack of consistent
communication were noted potential barriers to SBIRT implementation. CONCLUSIONS:
Clinicians expressed concerns about competing priorities and the need for
organizational leadership involvement for successful SBIRT implementation. A
unique suggestion for successful implementation is to utilize existing primary
care clinic-based psychologists to conduct brief intervention and facilitate
referral to treatment. Patient stakeholders supported universal screening, but
cultural differences in opinions and current experience were noted, indicating
the importance of including this perspective when evaluating implementation
potential.
PMID- 25127074
TI - Conserved electrostatic fields at the Ras-effector interface measured through
vibrational Stark effect spectroscopy explain the difference in tilt angle in the
Ras binding domains of Raf and RalGDS.
AB - Vibrational Stark effect (VSE) spectroscopy was used to measure the electrostatic
fields present at the interface of the human guanosine triphosphatase (GTPase)
Ras docked with the Ras binding domain (RBD) of the protein kinase Raf. Nine
amino acids located on the surface of Raf were selected for labeling with a
nitrile vibrational probe. Eight of the probe locations were situated along the
interface of Ras and Raf, and one probe was 2 nm away on the opposite side of
Raf. Vibrational frequencies of the nine Raf nitrile probes were compared both in
the monomeric, solvated protein and when docked with wild-type (WT) Ras to
construct a comprehensive VSE map of the Ras-Raf interface. Molecular dynamics
(MD) simulations employing an umbrella sampling strategy were used to generate a
Boltzmann-weighted ensemble of nitrile positions in both the monomeric and docked
complexes to determine the effect that docking has on probe location and
orientation and to aid in the interpretation of VSE results. These results were
compared to an identical study that was previously conducted on nine nitrile
probes on the RBD of Ral guanidine dissociation stimulator (RalGDS) to make
comparisons between the docked complexes formed when either of the two effectors
bind to WT Ras. This comparison finds that there are three regions of conserved
electrostatic fields that are formed upon docking of WT Ras with both downstream
effectors. Conservation of this pattern in the docked complex then results in
different binding orientations observed in otherwise structurally similar
proteins. This work supports an electrostatic cause of the known binding tilt
angle between the Ras-Raf and Ras-RalGDS complexes.
PMID- 25127076
TI - Dynamics of Back Electron Transfer in Dye-Sensitized Solar Cells Featuring 4-tert
Butyl-Pyridine and Atomic-Layer-Deposited Alumina as Surface Modifiers.
AB - A series of dye-sensitized solar cells (DSCs) was constructed with TiO2
nanoparticles and N719 dye. The standard I3(-)/I(-) redox shuttle and the Co(1,10
phenanthroline)3(3+/2+) shuttle were employed. DSCs were modified with atomic
layered-deposited (ALD) coatings of Al2O3 and/or with the surface-adsorbing
additive 4-tert-butyl-pyridine. Current-voltage data were collected to ascertain
the influence of each modification upon the back electron transfer (ET) dynamics
of the DSCs. The primary effect of the additives alone or in tandem is to
increase the open-circuit voltage. A second is to alter the short-circuit current
density, JSC. With dependence on the specifics of the system examined, any of a
myriad of dynamics-related effects were observed to come into play, in both
favorable (efficiency boosting) and unfavorable (efficiency damaging) ways. These
effects include modulation of (a) charge-injection yields, (b) rates of
interception of injected electrons by redox shuttles, and (c) rates of
recombination of injected electrons with holes on surface-bound dyes. In turn,
these influence charge-collection lengths, charge-collection yields, and onset
potentials for undesired dark current. The microscopic origins of the effects
appear to be related mainly to changes in driving force and/or electronic
coupling for underlying component redox reactions. Perhaps surprisingly, only a
minor role for modifier-induced shifts in conduction-band-edge energy was found.
The combination of DSC-efficiency-relevant effects engendered by the modifiers
was found to vary substantially as a function of the chemical identity of the
redox shuttle employed. While types of modifiers are effective, a challenge going
forward will be to construct systems in ways in which the benefits of organic and
inorganic modifiers can be exploited in fully additive, or even synergistic,
fashion.
PMID- 25127078
TI - Membrane surface engineering for protein separations: experiments and
simulations.
AB - A bisphosphonate derived ligand was successfully synthesized and grafted from the
surface of regenerated cellulose membrane using atom transfer radical
polymerization (ATRP) for protein separations. This ligand has a remarkable
affinity for arginine (Arg) residues on protein surface. Hydrophilic residues N
(2-hydroxypropyl) methacrylamide (HPMA) was copolymerized to enhance the
flexibility of the copolymer ligand and further improve specific protein
adsorption. The polymerization of bisphosphonate derivatives was successful for
the first time using ATRP. Static and dynamic binding capacities were determined
for binding and elution of Arg rich lysozyme. The interaction mechanism between
the copolymer ligand and lysozyme was elucidated using classical molecular
dynamics (MD) simulations.
PMID- 25127075
TI - Reactivity of damaged pyrimidines: DNA cleavage via hemiaminal formation at the
C4 positions of the saturated thymine of spore photoproduct and dihydrouridine.
AB - Described here are mechanistic details of the chemical reactivities of two
modified/saturated pyrimidine residues that represent naturally occurring forms
of DNA damage: 5-thyminyl-5,6-dihydrothymine, commonly referred to as the "spore
photoproduct" (SP), and 5,6-dihydro-2'-deoxyuridine (dHdU), formed via ionizing
radiation damage to cytosine under anoxic conditions and also serving as a
general model of saturated pyrimidine residues. It is shown that due to the loss
of the pyrimidine C5-C6 double bond and consequent loss of ring aromaticity, the
C4 position of both these saturated pyrimidines is prone to the formation of a
hemiaminal intermediate via water addition. Water addition is facilitated by
basic conditions; however, it also occurs at physiological pH at a slower rate.
The hemiaminal species so-formed subsequently converts to a ring-opened
hydrolysis product through cleavage of the pyrimidine N3-C4 bond. Further
decomposition of this ring-opened product above physiological pH leads to DNA
strand break formation. Taken together, these results suggest that once the
aromaticity of a pyrimidine residue is lost, the C4 position becomes a "hot spot"
for the formation of a tetrahedral intermediate, the decay of which triggers a
cascade of elimination reactions that can under certain conditions convert a
simple nucleobase modification into a DNA strand break.
PMID- 25127077
TI - Gynecologic care for transgender youth.
AB - PURPOSE OF REVIEW: To provide an overview of the care of the adolescent
transgender patient with regard to the guidelines and recommendations that
currently exist, and to review the role of the clinician caring for transgender
youth. RECENT FINDINGS: The World Professional Association for Transgender Health
and the Endocrine Society continue to provide comprehensive guidelines for the
care of adolescent transgender patients. The decision to perform surgery on a
patient who is a minor remains a complex one, and a case-by-case approach should
be taken with important ethical principles in mind. Cross-sex steroid use places
transgender adolescents at risk for metabolic disorders, and careful surveillance
is necessary. In addition, transgender teens are at high risk for depression,
anxiety and suicidality and have been shown to engage in more high-risk behaviors
compared with their nontransgender heterosexual counterparts. SUMMARY: Clinicians
who care for adolescents can play an important role in the counseling, screening,
health maintenance and support of their patients through the transition process.
PMID- 25127079
TI - A nurse-managed advocacy clinic in a Hispanic senior center: using a concept
based clinical practice site to enhance nursing education.
AB - A nurse-managed advocacy clinic for vulnerable, low-income, non-English-speaking
elderly Hispanic men and women was developed at a neighborhood community center
as a clinical site for senior baccalaureate nursing students. In the clinic's 5
years of operation, nursing students and faculty provided health screenings and
education as well as referrals to primary care providers, landlords, pharmacies,
and social workers. In doing so, nursing students were introduced to the concept
of patient advocacy in a real-world experiential clinical setting, providing an
effective link between theoretical knowledge discussed in the classroom and
professional nursing practice.
PMID- 25127080
TI - Comparison of student experience with critical events during simulation and acute
care hospital rotations.
AB - An exploratory study was conducted to determine critical events for adult
patients and to verify critical events that nursing students experienced in their
nursing programs. Sophomores and juniors were surveyed regarding frequency of
exposure to critical events. Sophomores reported greater differences between
simulation and clinical practice, with most in simulation. Juniors were more
balanced in exposure to critical events, in both clinical practice and
simulation. This information provides feedback on critical events, clinical
experiences, and how to use simulation to lessen the experience gap.
PMID- 25127081
TI - Evaluation of instruments developed to measure the clinical learning environment:
an integrative review.
AB - The nature of the clinical learning environment has a huge impact on student
learning. This article reviews current methods available for evaluating the
clinical learning environment. Five instruments were identified that measure the
clinical learning environment. All of these instruments focus solely on the
student perspective of the clinical learning environment. Although gaining
student input is important, there are other perspectives that offer valuable
insights on the nature of the clinical learning environment. The findings from
this integrative review indicate the need for future development and testing of
an instrument to evaluate the clinical learning environment from the staff nurse
and nurse faculty perspective.
PMID- 25127082
TI - Post-stress rumination predicts HPA axis responses to repeated acute stress.
AB - Failure of the hypothalamus-pituitary-adrenal (HPA) axis to habituate to repeated
stress exposure is related with adverse health outcomes, but our knowledge of
predictors of non-habituation is limited. Rumination, defined as repetitive and
unwanted past-centered negative thinking, is related with exaggerated HPA axis
stress responses and poor health outcomes. The aim of this study was to test
whether post-stress rumination was related with non-habituation of cortisol to
repeated stress exposure. Twenty-seven participants (n=13 females) were exposed
to the Trier Social Stress Test (TSST) twice on consecutive afternoons. Post
stress rumination was measured after the first TSST, and HPA axis responses were
assessed by measuring salivary cortisol 1 min before, and 1, 10, 20, 60, and 120
min after both TSSTs. Stress exposure induced HPA axis activation on both days,
and this activation showed habituation indicated by lower responses to the second
TSST (F=3.7, p=0.015). Post-stress rumination after the first TSST was associated
with greater cortisol reactivity after the initial stress test (r=0.45, p<0.05)
and with increased cortisol responses to the second TSST (r=0.51, p<0.01),
indicating non-habituation, independently of age, sex, depressive symptoms,
perceived life stress, and trait rumination. In summary, results showed that
rumination after stress predicted non-habituation of HPA axis responses. This
finding implicates rumination as one possible mechanism mediating maladaptive
stress response patterns, and it might also offer a pathway through which
rumination might lead to negative health outcomes.
PMID- 25127083
TI - Peptide YY and ghrelin predict craving and risk for relapse in abstinent smokers.
AB - Appetite hormones are directly involved in regulating satiety, energy
expenditure, and food intake, and accumulating evidence suggests their
involvement in regulating reward and craving for drugs. This study investigated
the ability of peptide YY (PYY) and ghrelin during the initial 24-48 h of a
smoking cessation attempt to predict smoking relapse at 4 weeks. Multiple
regression analysis indicated that increased PYY was associated with decreased
reported craving and increased positive affect. Cox proportional hazard models
showed that higher ghrelin levels predicted increased risk of smoking relapse
(hazard ratio=2.06, 95% CI=1.30-3.27). These results indicate that circulating
PYY may have buffering effects during the early stages of cessation while ghrelin
may confer increased risk of smoking relapse. Further investigation of the links
between these hormones and nicotine dependence is warranted.
PMID- 25127084
TI - Effect of restorative yoga vs. stretching on diurnal cortisol dynamics and
psychosocial outcomes in individuals with the metabolic syndrome: the PRYSMS
randomized controlled trial.
AB - PURPOSE: Chronic stimulation and dysregulation of the neuroendocrine system by
stress may cause metabolic abnormalities. We estimated how much cortisol and
psychosocial outcomes improved with a restorative yoga (relaxation) versus a low
impact stretching intervention for individuals with the metabolic syndrome.
METHODS: We conducted a 1-year multi-center randomized controlled trial (6-month
intervention and 6-month maintenance phase) of restorative yoga vs. stretching.
Participants completed surveys to assess depression, social support, positive
affect, and stress at baseline, 6 months and 12 months. For each assessment, we
collected saliva at four points daily for three days and collected response to
dexamethasone on the fourth day for analysis of diurnal cortisol dynamics. We
analyzed our data using multivariate regression models, controlling for study
site, medications (antidepressants, hormone therapy), body mass index, and
baseline cortisol values. RESULTS: Psychosocial outcome measures were available
for 171 study participants at baseline, 140 at 6 months, and 132 at 1 year.
Complete cortisol data were available for 136 of 171 study participants (72 in
restorative yoga and 64 in stretching) and were only available at baseline and 6
months. At 6 months, the stretching group had decreased cortisol at waking and
bedtime compared to the restorative yoga group. The pattern of changes in stress
mirrored this improvement, with the stretching group showing reductions in
chronic stress severity and perseverative thoughts about their stress. Perceived
stress decreased by 1.5 points (-0.4; 3.3, p=0.11) at 6 months, and by 2.0 points
(0.1; 3.9, p=0.04) at 1 year in the stretching compared to restorative yoga
groups. Post hoc analyses suggest that in the stretching group only, perceived
increases in social support (particularly feelings of belonging), but not changes
in stress were related to improved cortisol dynamics. CONCLUSIONS: We found
significant decreases in salivary cortisol, chronic stress severity, and stress
perception in the stretching group compared to the restorative yoga group. Group
support during the interactive stretch classes may have contributed to these
changes.
PMID- 25127086
TI - Who is stressed? A pilot study of salivary cortisol and alpha-amylase
concentrations in agoraphobic patients and their novice therapists undergoing in
vivo exposure.
AB - In cognitive behavioural therapy of phobic anxiety, in vivo exposure is
considered as an effective treatment strategy. Apparently, it involves the
experience of stress and anxiety in patients. Given the therapist's role during
exposure sessions, it is conceivable that the performance is also accompanied
with the experience of stress in therapists, especially when unversed in
conducting psychotherapy. Studies confirmed that cognitive behavioural therapists
tend to avoid therapist-guided in vivo exposure. The objective of this study was
the simultaneous investigation of therapist's and patient's stress response
during in vivo exposure. Therefore, 23 agoraphobic patients and their 23 treating
therapists in training provided five saliva samples during an in vivo exposure
and five samples during an ordinary therapy session. Before and during exposure
session, subjective evaluations of stress and anxiety were assessed. Results
suggested that therapists reported similar levels of perceived stress as patients
before exposure. Both groups displayed significantly elevated salivary cortisol
(sC) levels during exposure compared to the control session and a trend for
alterations in salivary alpha-amylase (sAA) activity was found. Therapists
reached peak concentrations of sC before start of the intervention followed by a
decline during exposure, while patients displayed peak levels of cortisol
secretion after 60 min of exposure. In vivo exposure seems to be a demanding
intervention not only for the patient, but also for therapists in training.
However, it was also demonstrated that physiological and subjective stress rather
decrease during the intervention and that both groups rated exposure to be
substantially successful. Based on the presented results, another potential
factor contributing to the under-usage of exposure treatment is conceivable and
needs to be addressed in future research.
PMID- 25127087
TI - Rewards and challenges of a career in research and teaching at a liberal arts
college.
PMID- 25127085
TI - Coping and glucocorticoid receptor regulation by stress inoculation.
AB - Intermittent exposure to mildly stressful situations provides opportunities to
practice coping in the context of exposure psychotherapies and stress inoculation
training. Previously, we showed that stress inoculation modeled in juvenile
monkeys enhances subsequent indications of resilience. Here we examine stress
inoculation effects in adult female monkeys. We found that stress inoculation
prevents social separation stress induced anhedonia measured using sucrose
preference tests and reduces the hypothalamic pituitary adrenal (HPA) axis stress
hormone response to a novel environment. Stress inoculation also increases
glucocorticoid receptor (NR3C1) gene expression in anterior cingulate cortex but
not hippocampus. Increased anterior cingulate cortex NR3C1 expression induced by
stress inoculation is not associated with significant changes in GR1F promoter
DNA methylation. On average, low levels of promoter DNA methylation and limited
GR1F expression were evident in monkey anterior cingulate cortex as observed in
corticolimbic brain regions of adult humans. Taken together these findings
suggest that stress inoculation in adulthood enhances behavioral and hormonal
aspects of coping without significantly influencing GR1F promoter DNA methylation
as a mechanism for NR3C1 transcription regulation.
PMID- 25127088
TI - Zebrafish bioassay-guided microfractionation identifies anticonvulsant steroid
glycosides from the Philippine medicinal plant Solanum torvum.
AB - Medicinal plants used for the treatment of epilepsy are potentially a valuable
source of novel antiepileptic small molecules. To identify anticonvulsant
secondary metabolites, we performed an in vivo, zebrafish-based screen of
medicinal plants used in Southeast Asia for the treatment of seizures. Solanum
torvum Sw. (Solanaceae) was identified as having significant anticonvulsant
activity in zebrafish larvae with seizures induced by the GABAA antagonist
pentylenetetrazol (PTZ). This finding correlates well with the ethnomedical use
of this plant in the Philippines, where a water decoction of S. torvum leaves is
used to treat epileptic seizures. HPLC microfractionation of the bioactive crude
extract, in combination with the in vivo zebrafish seizure assay, enabled the
rapid localization of several bioactive compounds that were partially identified
online by UHPLC-TOF-MS as steroid glycosides. Targeted isolation of the active
constituents from the methanolic extract enabled the complete de novo structure
identification of the six main bioactive compounds that were also present in the
traditional preparation. To partially mimic the in vivo metabolism of these
triterpene glycosides, their common aglycone was generated by acid hydrolysis.
The isolated molecules exhibited significant anticonvulsant activity in zebrafish
seizure assays. These results underscore the potential of zebrafish bioassay
guided microfractionation to rapidly identify novel bioactive small molecules of
natural origin.
PMID- 25127090
TI - Continuous subcutaneous hydrocortisone infusion therapy in Addison's disease: a
randomized, placebo-controlled clinical trial.
AB - CONTEXT: Patients with Addison's disease (AD) report impaired subjective health
status (SHS). Since cortisol exhibits a robust circadian cycle that entrains
other biological clocks, impaired SHS may be due to the noncircadian cortisol
profile achieved with conventional glucocorticoid replacement. Continuous
subcutaneous hydrocortisone infusion (CSHI) reproduces a circadian cortisol
profile, but its effects on SHS have not been objectively evaluated. OBJECTIVE:
The aim of this study was to determine the effect of CSHI on SHS in AD. SETTING
AND DESIGN: This was a multicentre, double-blind, placebo-controlled trial of
CSHI vs oral glucocorticoid therapy. Participants received in random order 4
weeks of: CSHI and oral placebo, and subcutaneous placebo and oral
hydrocortisone, separated by a 2-week washout period. SHS was assessed using the
Short-Form 36 (SF-36), General Health Questionnaire (GHQ-28), Fatigue Scale (FS),
Gastrointestinal Symptom Rating Scale (GSRS); and Addison's Quality of Life
Questionnaire (AddiQoL). Participants were asked their (blinded) treatment
preference. Twenty-four hour urine free cortisol (UFC) and diurnal salivary
cortisol collections compared cortisol exposure during each treatment. RESULTS:
Ten participants completed the study. Baseline SHS scores (mean +/- SE) were
consistent with mild impairment: SF-36 physical component summary 48.4 (+/- 2.4),
mental component summary 53.3 (+/- 3.0); GHQ-28 18.1 (+/- 3.3); GSRS 3.7 (+/-
1.6), and AddiQoL 94.7 (+/- 3.7). FS was similar to other AD cohorts 13.5 (+/-
1.0) (P = 0.82). UFC between treatments was not different (P = 0.87). The
salivary cortisol at 0800 h was higher during CSHI (P = 0.03), but not at any
other time points measured. There was no difference between the treatments in the
SHS assessments. Five participants preferred CSHI, four oral hydrocortisone, and
one was uncertain. CONCLUSIONS: Biochemical measurements indicate similar
cortisol exposure during each treatment period, although a more circadian pattern
was evident during CSHI. CSHI does not improve SHS in AD with good baseline SHS.
This casts some doubt on the potential benefit of circadian cortisol delivery on
SHS in AD.
PMID- 25127091
TI - Normal bone density and fat mass in heterozygous SERPINF1 mutation carriers.
AB - CONTEXT: Homozygous mutations in SERPINF1 cause deficiency of pigment epithelium
derived factor (PEDF) and lead to osteogenesis imperfecta (OI) type VI, but it is
not known whether heterozygous mutations in SERPINF1 cause a phenotype.
OBJECTIVE: In the present study, we therefore assessed family members of
individuals with OI type VI and compared the results of SERPINF1 mutation
carriers with those of noncarriers of SERPINF1 mutations. SETTING: This study was
conducted at a metabolic bone clinic of a pediatric orthopedic hospital.
SUBJECTS: The study population comprised 29 family members (age range 8-89 y; 18
females, 11 males) of patients with a diagnosis of OI type VI. Eighteen
individuals were heterozygous for SERPINF1 mutations, but the others did not
carry a mutation. MAIN OUTCOME MEASURES: PEDF expression was assessed in skin
fibroblasts from four heterozygous SERPINF1 mutation carriers. Skeletal
characteristics and body composition were measured using dual-energy X-ray
absorptiometry and peripheral quantitative computed tomography. Serum samples
were used to quantify markers of bone metabolism, lipid status, and PEDF.
RESULTS: Carriers of heterozygous stop or frame shift mutations in SERPINF1 had
low SERPINF1 transcript levels. Mean PEDF serum concentrations were significantly
lower in the carrier group than in the noncarriers (P = .04). However, no group
differences were found with regard to areal bone density at the lumbar spine and
total body, volumetric bone density at the radius and tibia, body composition,
lipid status, and markers of bone metabolism. CONCLUSION: Heterozygous SERPINF1
mutation carriers had no detectable abnormalities in fat and bone, despite
decreased PEDF expression.
PMID- 25127092
TI - Ectopic prolactin secretion from a perivascular epithelioid cell tumor (PEComa).
AB - BACKGROUND: The diagnosis of ectopic pituitary hormone secretion requires
abnormally high circulating hormone levels, absence of a pituitary tumor, and
localization of the hormone in question to the extrapituitary malignant neoplasm.
No case of a malignant solid tumor producing prolactin has been documented thus
far. CASE REPORT: A 47-year-old woman presented with amenorrhea and galactorrhea
of 3-year duration. Serum prolactin ranged from 300 to > 900 ng/mL, and other
pituitary and thyroid indices were normal, including testing for
macroprolactinemia. Pituitary magnetic resonance imaging revealed a partially
empty sella but no tumor. Cabergoline 0.5 mg twice weekly did not affect her
prolactinemia (1700 to 1900 ng/mL), and the medication was stopped. In the
meantime, she developed abdominal pain, and a computed tomography scan showed a
17 * 13 * 8-cm mass abutting the distal stomach, proximal duodenum, and right
colon. After the tumor was excised, her galactorrhea resolved, menstrual
periodicity resumed within the first month, and serum prolactin fell to 5 ng/mL.
Pathological examination of the excised tumor was consistent with perivascular
epithelioid cell tumor. Between 5 and 10% of the tumor cells were strongly
positive for prolactin on immunohistochemistry. RT-PCR detected prolactin mRNA in
the tumor cell extract, confirming the diagnosis of ectopic prolactin synthesis
and secretion. CONCLUSION: We present the first example of massive and
symptomatic hyperprolactinemia due to ectopic prolactin production by a solid
extrapituitary mesenchymal tumor confirmed with both mRNA analysis and
immunohistochemistry. Ectopic prolactin secretion should be suspected in patients
with a prolactin >200 ng/mL and negative sellar MRI.
PMID- 25127093
TI - Conjunctival UV autofluorescence--prevalence and risk factors.
AB - PURPOSE: Autofluorescence of ultraviolet (UV) light has been shown to occur in
localised areas of the bulbar conjunctiva, which map to active cellular changes
due to UV and environmental exposure. This study examined the presence of
conjunctival UV autofluorescence in eye care practitioners (ECPs) across Europe
and the Middle East and its associated risk factors. METHOD: Images were captured
of 307 ECPs right eyes in the Czech Republic, Germany, Greece, Kuwait,
Netherlands, Sweden, Switzerland, United Arab Emirates and the United Kingdom
using a Nikon D100 camera and dual flash units through UV filters. UV
autofluorescence was outlined using ImageJ software and the nasal and temporal
area quantified. Subjects were required to complete a questionnaire on their
demographics and lifestyle including general exposure to UV and refractive
correction. RESULTS: Average age of the subjects was 38.5+/-12.2 years (range 19
68) and 39.7% were male. Sixty-two percent of eyes had some conjunctival damage
as indicated by UV autofluorescence. The average area of damage was higher
(p=0.005) nasally (2.95+/-4.52mm(2)) than temporally (2.19+/-4.17mm(2)). The area
of UV damage was not related to age (r=0.03, p=0.674), gender (p=0.194), self
reported sun exposure lifestyle (p>0.05), geographical location (p=0174),
sunglasses use (p>0.05) or UV-blocking contact lens use (p>0.05), although it was
higher in those wearing contact lenses with minimal UV-blocking and no spectacles
(p=0.015). The area of UV damage was also less nasally in those who wore contact
lenses and spectacles compared to those with no refractive correction use
(p=0.011 nasal; p=0.958 temporal). CONCLUSION: UV conjunctival damage is common
even in Europe, Kuwait and UAE, and among ECPs. The area of damage appears to be
linked with the use of refractive correction, with greater damage nasally than
temporally which may be explained by the peripheral light focusing effect.
PMID- 25127089
TI - Abnormalities in cortical bone, trabecular plates, and stiffness in
postmenopausal women treated with glucocorticoids.
AB - CONTEXT: The mechanisms by which glucocorticoids (GCs) increase skeletal
fragility are not well understood. OBJECTIVE: The objective of the study was to
evaluate the microarchitecture, trabecular morphology, and biomechanical
properties of bone in postmenopausal women treated with GCs. DESIGN: This was a
case-control study. SETTING: The study was conducted at a university hospital
outpatient facility. PATIENTS: Postmenopausal women treated with oral GCs for
longer than 3 months (n = 30) and age/race-matched controls (n = 60) participated
in the study. MAIN OUTCOME MEASURES: Areal bone mineral density aBMD (BMD) by
dual-energy x-ray absorptiometry (DXA) was measured. Trabecular and cortical
volumetric BMD (vBMD) and microarchitecture by high-resolution peripheral
computed tomography of the distal radius and tibia were also measured. Whole-bone
stiffness was estimated by finite element analysis. A novel technique, individual
trabecula segmentation, was used to evaluate trabecular type (as plate or rod),
orientation, and connectivity. RESULTS: DXA T-scores did not differ significantly
at any site. GC subjects had significantly lower total, cortical, and trabecular
vBMD and thinner cortices, fewer, thinner, more widely, and irregularly spaced
trabeculae. They had fewer trabecular plates, fewer axially aligned trabeculae,
and lower trabecular connectivity. Differences ranged from 4% to 65% for these
trabecular measures and 5% to 17% for the cortical measures. Whole-bone stiffness
was significantly lower (11%-16%) in GC subjects. Markers of bone formation
(osteocalcin and amino-terminal propeptide of type I procollagen) and resorption
(C-telopeptide) were lower in the GC subjects. CONCLUSIONS: Despite similar areal
BMD by DXA, GC-treated women had abnormal cortical and trabecular vBMD and
microarchitecture at both the radius and tibia, including fewer trabecular
plates, a less axially aligned trabecular network, lower trabecular connectivity,
thinner cortices, and lower whole-bone stiffness. Further research into these
abnormalities as mechanisms for fracture in GC-treated women is warranted.
PMID- 25127094
TI - Rhabdoid differentiation is associated with aggressive behavior in renal cell
carcinoma: a clinicopathologic analysis of 76 cases with clinical follow-up.
AB - Rhabdoid differentiation has been associated with aggressive behavior in
carcinomas from different organ systems. A recent consensus statement of the
International Society of Urological Pathology (ISUP), in addition to proposing a
nucleolar grading system (ISUP grade) for renal cell carcinoma (RCC) to replace
the Fuhrman system, recommended reporting the presence of rhabdoid
differentiation in RCC and considering tumors with rhabdoid differentiation to be
ISUP grade 4. Although it has been shown that rhabdoid differentiation is
associated with increased grade and stage of RCC, it has not been fully
demonstrated whether it has an adverse effect independent of this association
with increased grade and stage. We provide the largest clinicopathologic analysis
of RCC with rhabdoid differentiation to date (76 cases), including
characterization of metastatic disease. In addition, by constructing a
multivariable model including tumor grade, stage, necrosis, and distant
metastasis to compare a series of 49 clear cell RCC with rhabdoid differentiation
with a cohort of 41 clear cell RCCs without rhabdoid differentiation, we
demonstrate that the presence of rhabdoid differentiation in clear cell RCC
confers an increased risk of death (hazard ratio=5.25; 95% confidence interval,
2.1-14.3) independent of these other adverse prognostic factors. These findings
underscore the significance of rhabdoid differentiation in RCC as an adverse
prognostic factor and support the recent reporting and grading recommendations of
the ISUP.
PMID- 25127095
TI - Morphologic and molecular characterization of traditional serrated adenomas of
the distal colon and rectum.
AB - Of the serrated polyps, the origin, morphologic features, molecular alterations,
and natural history of traditional serrated adenomas (TSAs) are the least
understood. Recent studies suggest that these polyps may arise from precursor
lesions. The frequencies of KRAS and BRAF mutations vary between these studies,
and only 1 small study has measured CpG island methylation using current markers
of methylation. Mutations in GNAS, a gene commonly mutated in colorectal villous
adenomas, have not been fully evaluated in TSAs. Finally, the expression of
annexin A10 (ANXA10), a recently discovered marker of sessile serrated
adenomas/polyps, has not been studied in these polyps. To further characterize
these polyps, 5 gastrointestinal pathologists reviewed 55 left-sided polyps
diagnosed as TSA at a single institution. Pathologists assessed various
histologic features including cytoplasmic eosinophilia, ectopic crypt foci,
presence of conventional dysplasia, and presence of precursor serrated lesions.
KRAS, BRAF, and GNAS mutational analysis was performed, as well as CpG island
methylation and ANXA10 immunohistochemistry. Ectopic crypt foci were seen in 62%
of TSAs. Precursor lesions were seen in 24% of the study polyps, most of which
were hyperplastic polyps. KRAS and BRAF mutations were common and were present in
42% and 48% of polyps, respectively. GNAS mutations occurred in 8% of polyps,
often in conjunction with a BRAF mutation. Unlike sessile serrated
adenomas/polyps, TSAs rarely had diffuse expression of ANXA10. Importantly, BRAF
mutated TSAs had more widespread methylation of a 5-marker CpG island panel
compared with KRAS-mutated polyps. However, ectopic crypt foci, a proposed
defining feature of TSA, were not associated with any specific molecular
alteration.
PMID- 25127096
TI - Estimation of normal computed tomography measurements for the upper cervical
spine in the pediatric age group.
AB - OBJECT: Upper cervical spine injuries in the pediatric age group have been
recognized as extremely unstable from ligamentous disruption and as potentially
lethal. Few measurement norms have been published for the pediatric upper
cervical spine to help diagnose this pathological state. Instead, adult
measurement techniques and results are usually applied inappropriately to
children. The authors propose using high-resolution reconstructed CT scans to
define a range of normal for a collection of selected upper cervical spine
measurements in the pediatric age group. METHODS: Sagittal and coronal
reformatted images were obtained from thin axial CT scans obtained in 42 children
(< 18 years) in a 2-month period. There were 25 boys and 17 girls. The mean age
was 100.9 months (range 1-214 months). Six CT scans were obtained for nontrauma
indications, and 36 were obtained as part of a trauma protocol and later cleared
for cervical spine injury. Six straightforward and direct linear distances-basion
dental interval (BDI); atlantodental interval (ADI); posterior atlantodental
interval (PADI); right and left lateral mass interval (LMI); right and left
craniocervical interval (CCI); and prevertebral soft-tissue thickness at C-2-that
minimized logistical and technical distortions were measured and recorded.
Statistical analysis including interobserver agreement, age stratification, and
sex differences was performed for each of the 6 measurements. RESULTS: The mean
ADI was 2.25 +/- 0.24 mm (+/- SD), the mean PADI was 18.3 +/- 0.07 mm, the mean
BDI was 7.28 +/- 0.10 mm, and the mean prevertebral soft tissue width at C-2 was
4.45 +/- 0.43 mm. The overall mean CCI was 2.38 +/- 0.44 mm, and the overall mean
LMI was 2.91 +/- 0.49 mm. Linear regression analysis demonstrated statistically
significant age effects for PADI (increased 0.02 mm/month), BDI (decreased 0.02
mm/month), and CCI (decreased 0.01 mm/month). Similarly significant effects were
found for sex; females demonstrated on average a smaller CCI by 0.26 mm and a
smaller PADI by 2.12 mm. Moderate to high interrater reliability was demonstrated
across all parameters. CONCLUSIONS: Age-dependent and age-independent normal CT
measurements of the upper cervical spine will help to differentiate physiological
and pathological states in children. The BDI appears to change significantly with
age but not sex; on the other hand, the LMI and ADI appear to be age-independent
measures. This preliminary study suggests acceptable levels of interrater
reliability, and further expanded study will aim to validate these measurements
to produce a profile of normal upper cervical spine measurements in children.
PMID- 25127097
TI - Brain metastases in patients diagnosed with a solid primary cancer during
childhood: experience from a single referral cancer center.
AB - OBJECT: Metastasis to the brain is frequent in adult cancer patients but rare
among children. Advances in primary tumor treatment and the associated prolonged
survival are said to have increased the frequency of brain metastasis in
children. The authors present a series of cases of brain metastases in children
diagnosed with a solid primary cancer, evaluate brain metastasis trends, and
describe tumor type, patterns of occurrence, and prognosis. METHODS: Patients
with brain metastases whose primary cancer was diagnosed during childhood were
identified in the 1990-2012 Tumor Registry at The University of Texas M.D.
Anderson Cancer Center. A review of their hospital records provided demographic
data, history, and clinical data, including primary cancer sites, number and
location of brain metastases, sites of extracranial metastases, treatments, and
outcomes. RESULTS: Fifty-four pediatric patients (1.4%) had a brain metastasis
from a solid primary tumor. Sarcomas were the most common (54%), followed by
melanoma (15%). The patients' median ages at diagnosis of the primary cancer and
the brain metastasis were 11.37 years and 15.03 years, respectively. The primary
cancer was localized at diagnosis in 48% of patients and disseminated regionally
in only 14%. The primary tumor and brain metastasis presented synchronously in
15% of patients, and other extracranial metastases were present when the primary
cancer was diagnosed. The remaining patients were diagnosed with brain metastasis
after initiation of primary cancer treatment, with a median presentation interval
of 17 months after primary cancer diagnosis (range 2-77 months). At the time of
diagnosis, the brain metastasis was the first site of systemic metastasis in only
4 (8%) of the 51 patients for whom data were available. Up to 70% of patients had
lung metastases when brain metastases were found. Symptoms led to the brain
metastasis diagnosis in 65% of cases. Brain metastases were single in 60% of
cases and multiple in 35%; 6% had only leptomeningeal disease. The median Kaplan
Meier estimates of survival after diagnoses of primary cancer and brain
metastasis were 29 months (95% CI 24-34 months) and 9 months (95% CI 6-11
months), respectively. Untreated patients survived for a median of 0.9 months
after brain metastasis diagnosis (95% CI 0.3-1.5 months). Those receiving
treatment survived for a median of 8 months after initiation of therapy (95% CI 6
11 months). CONCLUSIONS: The results of this study challenge the current notion
of an increased incidence of brain metastases among children with a solid primary
cancer. The earlier diagnosis of the primary cancer, prior to its dissemination
to distant sites (especially the brain), and initiation of presumably more
effective treatments may support such an observation. However, although the
actual number of cases may not be increasing, the prognosis after the diagnosis
of a brain metastasis remains poor regardless of the management strategy.
PMID- 25127100
TI - The deformation of B4C particle in the B4C/2024Al composites after high velocity
impact.
AB - In the present work, B4C/2024Al composites with volume fraction of 45% were
prepared by a pressure infiltration method. The microstructure of the crater
bottom of B4C/2024Al composite after impact was characterized by transmission
electron microscope (TEM), which indicated that recovery and dynamic
recrystallization generated in Al matrix, and the grain size distribution was
about from dozens of nanometer to 200 nm. Furthermore, the plastic deformation
was observed in B4C ceramic, which led to the transformation from monocrystal to
polycrystal ceramic grains. The boundary observed in this work was high-angle
grain boundary and the two grains at the boundary had an orientation difference
of 30 degrees .
PMID- 25127099
TI - Enterocutaneous fistula in the setting of ventriculoperitoneal shunt extrusion
through the skin and perforation through the small bowel.
AB - The authors report a case of a 2-year-old boy with postinfectious hydrocephalus,
managed with a ventriculoperitoneal (VP) shunt and complicated by shunt extrusion
through the cranial skin. The shunt was removed due to concern for infection, and
the child was found to have an enterocutaneous fistula (ECF) communicating along
the shunt track between the small bowel and a clavicular sinus. Self-closure of
the ECF was anticipated. Thus, the fistula was managed expectantly with dressing
changes of the clavicular sinus, while the patient's malnutrition was managed in
accordance with World Health Organization protocols. The presentation, prognosis
and management of ECFs, including the likelihood of self-resolution and the role
of expectant management, are discussed. Additionally, proposed mechanisms of ECF
formation in the setting of a VP shunt are discussed, with an emphasis on the
roles of infection and malnutrition.
PMID- 25127098
TI - Epilepsy surgery failure in children: a quantitative and qualitative analysis.
AB - OBJECT: Resection is a safe and effective treatment option for children with
pharmacoresistant focal epilepsy, but some patients continue experience seizures
after surgery. While most studies of pediatric epilepsy surgery focus on
predictors of postoperative seizure outcome, these factors are often not
modifiable, and the reasons for surgical failure may remain unclear. METHODS: The
authors performed a retrospective cohort study of children and adolescents who
received focal resective surgery for pharmacoresistant epilepsy. Both
quantitative and qualitative analyses of factors associated with persistent
postoperative seizures were conducted. RESULTS: Records were reviewed from 110
patients, ranging in age from 6 months to 19 years at the time of surgery, who
underwent a total of 115 resections. At a mean 3.1-year follow-up, 76% of
patients were free of disabling seizures (Engel Class I outcome). Seizure freedom
was predicted by temporal lobe surgery compared with extratemporal resection,
tumor or mesial temporal sclerosis compared with cortical dysplasia or other
pathologies, and by a lower preoperative seizure frequency. Factors associated
with persistent seizures (Engel Class II-IV outcome) included residual
epileptogenic tissue adjacent to the resection cavity (40%), an additional
epileptogenic zone distant from the resection cavity (32%), and the presence of a
hemispheric epilepsy syndrome (28%). CONCLUSIONS: While seizure outcomes in
pediatric epilepsy surgery may be improved by the use of high-resolution
neuroimaging and invasive electrographic studies, a more aggressive resection
should be considered in certain patients, including hemispherectomy if a
hemispheric epilepsy syndrome is suspected. Family counseling regarding treatment
expectations is critical, and reoperation may be warranted in select cases.
PMID- 25127101
TI - Discovery of furan-2-carbohydrazides as orally active glucagon receptor
antagonists.
AB - Furan-2-carbohydrazides were found as orally active glucagon receptor
antagonists. Starting from the hit compound 5, we successfully determined the
structure activity relationships of a series of derivatives obtained by modifying
the acidity of the phenol. We identified the ortho-nitrophenol as a good scaffold
for glucagon receptor inhibitory activity. Our efforts have led to the discovery
of compound 7l as a potent glucagon receptor antagonist with good bioavailability
and satisfactory long half-life.
PMID- 25127102
TI - Development of chiral praziquantel analogues as potential drug candidates with
activity to juvenile Schistosoma japonicum.
AB - A series of chiral praziquantel analogues were synthesized and evaluated against
Schistosoma japonicum both in vitro and in vivo. All compounds exhibited low to
considerable good activity in vivo. Remarkably, worm reduction rate of R-3 was
60.0% at a single oral dose of 200mg/kg against juvenile stage of Schistosoma
japonicum. The target compounds displayed in vivo antischistosomal activity
against both Schistosoma japonicum and Schistosoma mansoni. Furthermore, all R
isomers displayed stronger antischistosomal activity than S-isomers in vivo,
indicating R-isomers were the active enantiomers, while S-isomers were less
active ones. This structure activity relationship (SAR) could have important
implications in further drug development for schistosomiasis.
PMID- 25127104
TI - A new series of HAPs as anti-HBV agents targeting at capsid assembly.
AB - A series of novel Heteroaryldihydropyrimidines (HAPs) derivatives were designed
and synthesized as potent inhibitors of HBV capsid assembly. These compounds were
prepared from efforts to optimize an earlier series of HAPs, and compounds Mo1,
Mo7, Mo8, Mo10, Mo12, and Mo13 demonstrated potent inhibition of HBV DNA
replication at submicromolar range.
PMID- 25127103
TI - Structural studies provide clues for analog design of specific inhibitors of
Cryptosporidium hominis thymidylate synthase-dihydrofolate reductase.
AB - Cryptosporidium is the causative agent of a gastrointestinal disease,
cryptosporidiosis, which is often fatal in immunocompromised individuals and
children. Thymidylate synthase (TS) and dihydrofolate reductase (DHFR) are
essential enzymes in the folate biosynthesis pathway and are well established as
drug targets in cancer, bacterial infections, and malaria. Cryptosporidium
hominis has a bifunctional thymidylate synthase and dihydrofolate reductase
enzyme, compared to separate enzymes in the host. We evaluated lead compound 1
from a novel series of antifolates, 2-amino-4-oxo-5-substituted pyrrolo[2,3
d]pyrimidines as an inhibitor of Cryptosporidium hominis thymidylate synthase
with selectivity over the human enzyme. Complementing the enzyme inhibition
compound 1 also has anti-cryptosporidial activity in cell culture. A crystal
structure with compound 1 bound to the TS active site is discussed in terms of
several van der Waals, hydrophobic and hydrogen bond interactions with the
protein residues and the substrate analog 5-fluorodeoxyuridine monophosphate
(TS), cofactor NADPH and inhibitor methotrexate (DHFR). Another crystal structure
in complex with compound 1 bound in both the TS and DHFR active sites is also
reported here. The crystal structures provide clues for analog design and for the
design of ChTS-DHFR specific inhibitors.
PMID- 25127105
TI - Evaluation of the cyclopentane-1,2-dione as a potential bio-isostere of the
carboxylic acid functional group.
AB - Cycloalkylpolyones hold promise in drug design as carboxylic acid bio-isosteres.
To investigate cyclopentane-1,2-diones as potential surrogates of the carboxylic
acid functional group, the acidity, tautomerism, and geometry of hydrogen bonding
of representative compounds were evaluated. Prototypic derivatives of the known
thromboxane A2 prostanoid (TP) receptor antagonist, 3-(3-(2-((4
chlorophenyl)sulfonamido)-ethyl)phenyl)propanoic acid, in which the carboxylic
acid moiety is replaced by the cyclopentane-1,2-dione unit, were synthesized and
evaluated as TP receptor antagonists. Cyclopentane-1,2-dione derivative 9 was
found to be a potent TP receptor antagonist with an IC50 value comparable to that
of the parent carboxylic acid. These results indicate that the cyclopentane-1,2
dione may be a potentially useful carboxylic acid bio-isostere.
PMID- 25127107
TI - Trends in boxed warnings and withdrawals for novel therapeutic drugs, 1996
through 2012.
PMID- 25127108
TI - Supportive care needs of cancer patients: A literature review.
AB - OBJECTIVE: This review of the research literature explored the supportive care
needs of cancer patients of varying ages and genders at varying stages of cancer
treatment. METHOD: We conducted a search of online databases of peer-reviewed
studies published in the English language between 2009 and 2014. RESULTS: This
paper reviews research studies that explored the supportive care needs of cancer
patients through focus groups, surveys, and interviews. The samples addressed
varied in age, ethnicity, and gender. SIGNIFICANCE OF RESULTS: One major need
identified was the requirement of informational support. Other essential needs
included emotional, spiritual, and financial support. Supportive care can be
administered in various ways-for example, by religious communities or caregivers
as well as providers. However, healthcare providers must recognize the supportive
care needs of their patients and incorporate effective resources and
interventions into treatment plans.
PMID- 25127106
TI - Polymorphisms in the TNFA and IL6 genes represent risk factors for autoimmune
thyroid disease.
AB - BACKGROUND: Autoimmune thyroid disease (AITD) comprises diseases including
Hashimoto's thyroiditis and Graves' disease, both characterized by reactivity to
autoantigens causing, respectively, inflammatory destruction and autoimmune
stimulation of the thyroid-stimulating hormone receptor. AITD is the most common
thyroid disease and the leading form of autoimmune disease in women. Cytokines
are key regulators of the immune and inflammatory responses; therefore, genetic
variants at cytokine-encoding genes are potential risk factors for AITD. METHODS:
Polymorphisms in the IL6-174 G/C (rs1800795), TNFA-308 G/A (rs1800629), IL1B-511
C/T (rs16944), and IFNGR1-56 T/C (rs2234711) genes were assessed in a case
control study comprising 420 Hashimoto's thyroiditis patients, 111 Graves'
disease patients and 735 unrelated controls from Portugal. Genetic variants were
discriminated by real-time PCR using TaqMan SNP genotyping assays. RESULTS: A
significant association was found between the allele A in TNFA-308 G/A and
Hashimoto's thyroiditis, both in the dominant (OR = 1.82, CI = 1.37-2.43, p-value
= 4.4*10(-5)) and log-additive (OR = 1.64, CI = 1.28-2.10, p-value = 8.2*10(-5))
models. The allele C in IL6-174 G/C is also associated with Hashimoto's
thyroiditis, however, only retained significance after multiple testing
correction in the log-additive model (OR = 1.28, CI = 1.06-1.54, p-value =
8.9*10(-3)). The group with Graves' disease also registered a higher frequency of
the allele A in TNFA-308 G/A compared with controls both in the dominant (OR =
1.85, CI = 1.19-2.87, p-value = 7.0*10(-3)) and log-additive (OR = 1.69, CI =
1.17-2.44, p-value = 6.6*10(-3)) models. The risk for Hashimoto's thyroiditis and
Graves' disease increases with the number of risk alleles (OR for two risk
alleles is, respectively, 2.27 and 2.59). CONCLUSIONS: This study reports
significant associations of genetic variants in TNFA and IL6 with the risk for
AITD, highlighting the relevance of polymorphisms in inflammation-related genes
in the etiopathogenesis of AITD.
PMID- 25127109
TI - Trans-axillary approach for breast implant exchange in high risk cases of
irradiated or attenuated skin.
AB - BACKGROUND: Breast reconstruction with implants after tissue expansion is one of
the most common methods of reconstruction. Although this approach is generally
reliable, exchange of breast tissue expander for implant through the standard
anterior incision presents a challenge in cases with attenuated soft tissue
envelope due to radiation, thin anatomy, prior surgery, or combination of the
above. We propose that a trans-axillary approach is a safe and alternate approach
for implant exchange in the high-risk patients. TECHNIQUE AND CASE EXAMPLES: A
case series of 16 patients with multiple risk factors for compromised soft tissue
that underwent a trans-axillary approach for implant exchange is reported. The
trans-axillary implant exchange technique involves use of a standard 4 cm
axillary incision, removal of the expander, judicious capsulotomy, placement of
permanent implant, and closure in three separate tissue layers. RESULTS: All
trans-axillary cases were successful and all incisions were well healed without
dehiscence, infection, or seroma. The average patient age was 49.4 years, and 50%
of patients had received or were scheduled to receive radiation therapy. Nine
patients underwent unilateral trans-axillary expander exchange while 7 patients
were bilateral. Median implant size was 360 cc (mean 369 cc, range 150-600 cc),
and mean follow-up for all patients was over 24 months. There were no cases of
implant extrusion, capsular contracture requiring re-operation, or lymphedema.
Six patients underwent concurrent or subsequent nipple reconstruction.
CONCLUSIONS: This approach illustrates application of a technique commonly used
in breast aesthetic augmentation to address a common reconstructive dilemma,
which we believe to be a useful tool in prosthesis-based breast reconstruction,
especially in patients with compromised soft tissue envelopes.
PMID- 25127110
TI - Updated S2K AWMF guideline for the diagnosis and follow-up of obstructive
sialadenitis--relevance for radiologic imaging.
AB - The interdisciplinarily developed German S2k AWMF guideline for the treatment of
obstructive sialadenitis represents a new standard in the guideline program of
the AWMF, the German Society for Consultants and the clinical disciplines working
in the field of diseases of the head and neck region. In the last few years new
diagnostic and therapeutic possibilities have been established in obstructive
chronic Sialadenitis offering individually optimized therapeutic strategies. Only
a few years ago extirpation of the whole affected gland was the only relevant
therapy option. Nowadays therapeutic options such as interventional sialendoscopy
and extracorporeal shock-wave lithotripsy (ESWL) are available in combination
with marsupialization or incision of the duct. If possible the focus is on
preserving the main glandular duct. In the following article the relevant aspects
for the diagnostic radiologic procedures are presented.
PMID- 25127111
TI - [Diagnostic error: lung cancer].
PMID- 25127112
TI - Potential utility of a new ulcerative colitis segmental endoscopic index
combining disease severity and the extent of inflammation.
AB - GOAL: To investigate the potential utility of a new scoring system, the
Ulcerative Colitis Segmental Endoscopic Index (UCSEI), which combines measures of
disease severity and extent of inflammation. BACKGROUND: Intestinal mucosal
healing (MH) is a new therapeutic goal for ulcerative colitis (UC). Discontinuous
lesions are common in UC and endoscopic observation of the entire colon is
important. STUDY: Patients with active mild-to-moderate UC received daily
treatment with oral mesalazine (4 g/d) and mesalazine enemas (1 g/d) for 8 weeks.
Endoscopic evaluations, using the UCSEI and Mayo Endoscopic Score (MES), were
performed in 5 colonic segments at baseline and week 8. The UCSEI criteria
included erythema, vascular pattern, friability, and erosion/ulcer. The sum of 5
subscores, determined for each segment, was calculated as the UCSEI. Disease
activity was also assessed using the UC Disease Activity Index (UCDAI). MH was
defined as MES=0 to 1. RESULTS: Of 58 patients, 51 completed the scheduled
endoscopic evaluations. At week 8, the UCDAI score had significantly decreased
from 6.63 (baseline) to 2.73 (P<0.001). The remission and MH rates were 35.3% and
55.3%, respectively. Segmental endoscopic evaluation, using UCSEI, showed that
baseline inflammation tended to be more severe in the distal colon. The baseline
UCSEI increased with the extent of disease, which was not seen in MES.
Improvements in UCSEI were observed, even in the patients without decreases in
the MES. CONCLUSIONS: UCSEI, reflecting disease severity and extent of
inflammation, provides useful information for UC management that is not available
with MES.
PMID- 25127113
TI - Transjugular Intrahepatic Portosystemic Shunt for Acute Variceal Bleeding: A Meta
analysis.
AB - BACKGROUND AND AIMS: Acute variceal bleeding is the most common lethal
complication of liver cirrhosis. A meta-analysis was conducted to compare the
outcomes of transjugular intrahepatic portosystemic shunt (TIPS) to those of
medical/endoscopic therapy for acute variceal bleeding in cirrhotic patients.
METHODS: The PubMed, EMBASE, and Cochrane Library databases were searched for all
relevant comparative studies. Odds ratios (OR) and hazard ratios (HR) with 95%
confidence intervals (CI)were pooled for dichotomous and time-dependent
variables, respectively. Subgroup analyses were performed according to the type
of study design (randomized or nonrandomized studies), source of bleeding
(esophageal or gastric varices), type of stent (covered or bare stent), and
patient selection (high risk or unselected patients). RESULTS: Six papers were
eligible. TIPS was superior to medical/endoscopic therapy in decreasing the
incidence of treatment failure (OR=0.22; 95% CI, 0.11-0.44), improving overall
survival (HR=0.55; 95% CI, 0.38-0.812), and decreasing the incidence of bleeding
related death (OR=0.19; 95% CI, 0.06-0.59). Although TIPS did not significantly
decrease the incidence of rebleeding (OR=0.27; 95% CI, 0.06-1.29), it became
significantly greater in the subgroup meta-analyses of randomized studies
(OR=0.09; 95% CI, 0.03-0.32) than in those of nonrandomized studies (OR=0.76; 95%
CI, 0.40-1.45; subgroup difference, P=0.003), and in the subgroup meta-analyses
of studies including high-risk patients (OR=0.06; 95% CI, 0.01-0.23) than in
those including low-risk patients (OR=0.83; 95% CI, 0.44-1.56; subgroup
difference, P=0.0007). In addition, TIPS did not significantly increase the
incidence of posttreatment hepatic encephalopathy (OR=1.37; 95% CI, 0.63-2.99).
CONCLUSIONS: With the exception of the benefit of prevention from treatment
failure, TIPS with covered stents might improve the overall survival of high-risk
patients with acute variceal bleeding.
PMID- 25127114
TI - Long-term Outcomes of Symptomatic Gallbladder Sludge.
AB - GOALS AND BACKGROUND: Long-term outcomes of symptomatic gallbladder (GB) sludge
are not fully established. This study aimed to determine whether patients with
symptomatic GB sludge could experience subsequent biliary events. STUDY: This
study investigated consecutive patients who presented with typical biliary pain
and underwent abdominal ultrasonography from March 2003 to December 2012. A
prospectively maintained database of these patients, excluding those with
gallstones, was reviewed retrospectively. We compared the development of biliary
events such as acute cholecystitis, acute cholangitis, and acute pancreatitis
between both GB sludge and non-GB sludge cohorts. RESULTS: In all, 58 and 70
patients were diagnosed with and without GB sludge, respectively. The 5-year
cumulative biliary event rate was significantly higher in the GB sludge (33.9%
vs. 15.8%, P=0.021) and the hazard ratio of subsequent biliary events was 2.573
(95% confidence interval, 1.124-5.889; P=0.025) in patients with GB sludge. The 5
year cumulative rate of each biliary event was higher in the GB sludge cohort
(15.6% vs. 5.3% in acute cholecystitis, 15.5% vs. 5.3% in acute cholangitis,
18.4% vs. 11.1% in acute pancreatitis, respectively), although it was not
statistically significant. Among the GB sludge cohort, subsequent biliary events
were less frequent in patients who underwent cholecystectomy compared with those
who did not (2/16, 12.5% vs. 17/42, 40.4%; P=0.067). CONCLUSIONS: GB sludge
accompanying typical biliary pain can cause subsequent biliary events and
cholecystectomy may prevent subsequent biliary events. Therefore, GB sludge would
be considered as a culprit of biliary events.
PMID- 25127115
TI - Rate of Recurrent Luminal Esophageal Cancer in Asymptomatic Patients After
Curative Treatment for Esophageal Cancer.
AB - GOALS: The goal of this study was to determine the luminal recurrence rate of
asymptomatic patients undergoing annual surveillance esophagogastroduodenoscopy
(EGD). BACKGROUND: Current guidelines recommend surveillance EGD in
postesophagectomy patients with esophageal cancer if there is clinical suspicion
of local recurrence. However, many patients undergo annual surveillance EGD
despite the recommendations to the contrary. STUDY: A query was performed of all
patients who underwent esophagectomy between January 2000 and April 2010 at
Moffitt Cancer Center. Patients were included if: they underwent esophagectomy
with curative intent, had at least 12 months of follow-up after surgery, and had
a R0 resection. Clinical and pathologic data in patients with and without
recurrent disease were compared using the Fisher exact tests. Mean differences
were examined using the Wilcoxon rank sum test. RESULTS: 346 patients were
included with a mean age of 63.5+/-10.4 years and mean follow-up of 40.9+/-24.8
months. Recurrence was detected in 89 (25.7%) patients at a mean follow-up of
17.9+/-15.9 months after surgery. Seventeen (19.1%) patients had recurrence
involving the esophagus but 7 (7.9%) patients had associated regional or distant
metastases. Nine patients had abnormal signs/symptoms prompting evaluation with
EGD. One patient had isolated luminal recurrence. CONCLUSIONS: In this study the
majority of patients recurred in the metastatic setting. One (0.29%) patient had
localized recurrence; however, it was unclear if this patient had any symptoms or
signs to prompt evaluation. Our results support the current recommendation of a
symptom-base endoscopic evaluation for esophageal cancer recurrence.
PMID- 25127117
TI - Outcome of pregnancy following second- or third-trimester intrauterine fetal
death.
AB - OBJECTIVE: To investigate the outcomes of a pregnancy after a second- or third
trimester intrauterine fetal death (IUFD). METHODS: A prospective observational
study was conducted at Trousseau Hospital (Paris, France) between 1996 and 2011.
The first ongoing pregnancy in women who had had a previous IUFD was monitored.
Management of their treatment was according to a standardized protocol.
Recurrence of fetal death was the main outcome criterion. RESULTS: The subsequent
pregnancies of 87 women who had experienced at least one previous IUFD were
followed up. The cause of previous IUFD was placental in 50 (57%) women, unknown
in 19 (22%), adnexal in 12 (14%), metabolic in 2 (2%), and malformative in 4
(5%). Three (3%) participants had another stillbirth. Overall, obstetric
complications occurred in 34 (39%) pregnancies (including 22 [25%] preterm
births, 5 [6%] small for gestational age, and 6 [7%] maternal vascular
complications). Obstetric complications were significantly more common among
women whose previous stillbirth had been due to placental causes than among those
affected by other causes (P=0.02). CONCLUSION: Most pregnancies after IUFD
resulted in a live birth; however, adverse obstetric outcomes were more common
when the previous stillbirth was due to placental causes.
PMID- 25127116
TI - Metformin protects cardiomyocyte from doxorubicin induced cytotoxicity through an
AMP-activated protein kinase dependent signaling pathway: an in vitro study.
AB - Doxorubicin (Dox) is one of the most widely used antitumor drugs, but its
cumulative cardiotoxicity have been major concerns in cancer therapeutic practice
for decades. Recent studies established that metformin (Met), an oral anti
diabetic drug, provides protective effects in Dox-induced cardiotoxicity. Met has
been shown to increase fatty acid oxidation, an effect mediated by AMP activated
protein kinase (AMPK). Here we delineate the intracellular signaling factors
involved in Met mediated protection against Dox-induced cardiotoxicity in the
H9c2 cardiomyoblast cell line. Treatment with low dose Met (0.1 mM) increased
cell viabilities and Ki-67 expressions while decreasing LDH leakages, ROS
generations and [Ca2+]i. The protective effect was reversed by a co-treatment
with compound-C, an AMPK specific inhibitor, or by an over expression of a
dominant-negative AMPKalpha cDNA. Inhibition of PKA with H89 or a suppression of
Src kinase by a small hairpin siRNA also abrogated the protective effect of the
low dose Met. Whereas, with a higher dose of Met (1.0 mM), the protective effects
were abolished regardless of the enhanced AMPK, PKA/CREB1 and Src kinase
activity. In high dose Met treated cells, expression of platelet-derived growth
factor receptor (PDGFR) was significantly suppressed. Furthermore, the protective
effect of low dose Met was totally reversed by co-treatment with AG1296, a PDGFR
specific antagonist. These data provide in vitro evidence supporting a signaling
cascade by which low dose Met exerts protective effects against Dox via
sequential involvement of AMPK, PKA/CREB1, Src and PDGFR. Whereas high dose Met
reverses the effect by suppressing PDGFR expression.
PMID- 25127118
TI - Neuronal cellular responses to extremely low frequency electromagnetic field
exposure: implications regarding oxidative stress and neurodegeneration.
AB - Neurodegenerative diseases comprise both hereditary and sporadic conditions
characterized by an identifying progressive nervous system dysfunction and
distinctive neuopathophysiology. The majority are of non-familial etiology and
hence environmental factors and lifestyle play key roles in their pathogenesis.
The extensive use of and ever increasing worldwide demand for electricity has
stimulated societal and scientific interest on the environmental exposure to low
frequency electromagnetic fields (EMFs) on human health. Epidemiological studies
suggest a positive association between 50/60-Hz power transmission fields and
leukemia or lymphoma development. Consequent to the association between EMFs and
induction of oxidative stress, concerns relating to development of
neurodegenerative diseases, such as Alzheimer disease (AD), have been voiced as
the brain consumes the greatest fraction of oxygen and is particularly vulnerable
to oxidative stress. Exposure to extremely low frequency (ELF)-EMFs are reported
to alter animal behavior and modulate biological variables, including gene
expression, regulation of cell survival, promotion of cellular differentiation,
and changes in cerebral blood flow in aged AD transgenic mice. Alterations in
inflammatory responses have also been reported, but how these actions impact
human health remains unknown. We hence evaluated the effects of an
electromagnetic wave (magnetic field intensity 1 mT; frequency, 50-Hz) on a well
characterized immortalized neuronal cell model, human SH-SY5Y cells. ELF-EMF
exposure elevated the expession of NOS and O2(-), which were countered by
compensatory changes in antioxidant catylase (CAT) activity and enzymatic kinetic
parameters related to CYP-450 and CAT activity. Actions of ELF-EMFs on cytokine
gene expression were additionally evaluated and found rapidly modified.
Confronted with co-exposure to H2O2-induced oxidative stress, ELF-EMF proved not
as well counteracted and resulted in a decline in CAT activity and a rise in O2(
) levels. Together these studies support the further evaluation of ELF-EMF
exposure in cellular and in vivo preclinical models to define mechanisms
potentially impacted in humans.
PMID- 25127119
TI - Oligosaccharide substrate preferences of human extracellular sulfatase Sulf2
using liquid chromatography-mass spectrometry based glycomics approaches.
AB - Sulfs are extracellular endosulfatases that selectively remove the 6-O-sulfate
groups from cell surface heparan sulfate (HS) chain. By altering the sulfation at
these particular sites, Sulfs function to remodel HS chains. As a result of the
remodeling activity, HSulf2 regulates a multitude of cell-signaling events that
depend on interactions between proteins and HS. Previous efforts to characterize
the substrate specificity of human Sulfs (HSulfs) focused on the analysis of HS
disaccharides and synthetic repeating units. In this study, we characterized the
substrate preferences of human HSulf2 using HS oligosaccharides with various
lengths and sulfation degrees from several naturally occurring HS sources by
applying liquid chromatography mass spectrometry based glycomics methods. The
results showed that HSulf2 preferentially digests highly sulfated HS
oligosaccharides with zero acetyl groups and this preference is length dependent.
In terms of length of oligosaccharides, HSulf2 digestion induced more sulfation
decrease on DP6 (DP: degree of polymerization) compared to DP2, DP4 and DP8. In
addition, the HSulf2 preferentially digests the oligosaccharide domain located at
the non-reducing end (NRE) of the HS and heparin chain. In addition, the HSulf2
digestion products were altered only for specific isomers. HSulf2 treated NRE
oligosaccharides also showed greater decrease in cell proliferation than those
from internal domains of the HS chain. After further chromatographic separation,
we identified the three most preferred unsaturated hexasaccharide for HSulf2.
PMID- 25127120
TI - Automated segmentation and quantification of white matter hyperintensities in
acute ischemic stroke patients with cerebral infarction.
AB - White matter hyperintensities (WMHs) of presumed vascular origin are common in
ageing population, especially in patients with acute cerebral infarction and the
volume has been reported to be associated with mental impairment and the risk of
hemorrhage from antithrombotic agents. WMHs delineation can be computerized to
minimize human bias. However, the presence of cerebral infarcts greatly degrades
the accuracy of WMHs detection and thus limits the application of computerized
delineation to patients with acute cerebral infarction. We propose a computer
assisted segmentation method to depict WMHs in the presence of cerebral infarcts
in combined T1-weighted, fluid attenuation inversion recovery, and diffusion
weighted magnetic resonance imaging (MRI). The proposed method detects WMHs by
empirical threshold and atlas information, with subtraction of white matter
voxels affected by acute infarction. The method was derived using MRI from 25
hemispheres with WMHs only and 13 hemispheres with both WMHs and cerebral
infarcts. Similarity index (SI) and correlation were utilized to assess the
agreement between the new automated method and a gold standard visually guided
semi-automated method done by an expert rater. The proposed WMHs segmentation
approach produced average SI, sensitivity and specificity of 83.142+/-11.742,
84.154+/-16.086 and 99.988+/-0.029% with WMHs only and of 68.826+/-14.036,
74.381+/-18.473 and 99.956+/-0.054% with both WMHs and cerebral infarcts in the
derivation cohort. The performance of the proposed method with an external
validation cohort was also highly consistent with that of the experienced rater.
PMID- 25127121
TI - Inhibition of c-Myc overcomes cytotoxic drug resistance in acute myeloid leukemia
cells by promoting differentiation.
AB - Nowadays, drug resistance still represents a major obstacle to successful acute
myeloid leukemia (AML) treatment and the underlying mechanism is not fully
elucidated. Here, we found that high expression of c-Myc was one of the
cytogenetic characteristics in the drug-resistant leukemic cells. c-Myc over
expression in leukemic cells induced resistance to chemotherapeutic drugs,
enhanced colony formation capacity and inhibited cell differentiation induced by
all-trans retinoic acid (ATRA). Meanwhile, inhibition of c-Myc by shRNA or
specific c-Myc inhibitor 10058-F4 rescued the sensitivity to cytotoxic drugs,
restrained the colony formation ability and promoted differentiation. RT-PCR and
western blotting analysis showed that down-regulation of C/EBPbeta contributed to
the poor differentiation state of leukemic cells induced by c-Myc over
expression. Importantly, over-expression of C/EBPbeta could reverse c-Myc induced
drug resistance. In primary AML cells, the c-Myc expression was negatively
correlated with C/EBPbeta. 10058-F4, displayed anti-proliferative activity and
increased cellular differentiation with up-regulation of C/EBPbeta in primary AML
cells. Thus, our study indicated that c-Myc could be a novel target to overcome
drug resistance, providing a new approach in AML therapy.
PMID- 25127122
TI - Image-based three-dimensional conformal brachytherapy for medically inoperable
endometrial carcinoma.
AB - PURPOSE: Definitive radiotherapy is a viable option for medically inoperable
patients with early stage endometrial cancer. We present our experience using
image-based brachytherapy (BT). METHODS AND MATERIALS: Patients with medically
inoperable clinical Stage I endometrial adenocarcinoma received definitive BT
with or without external beam radiotherapy. High-dose-rate BT was delivered using
MRI- or CT-based planning for each fraction. For patients with an MRI, gross
tumor volume (GTV) was contoured although dose was still prescribed to the
clinical treatment volume (CTV), including the entire uterus, cervix, and upper 1
2 cm of vagina. Equivalent 2 Gy doses (EQD2) were calculated. RESULTS: Thirty
eight patients were treated from 2007 to 2013, 20 receiving BT alone with a
median dose of 37.5 Gy in five to six fractions. For combined therapy, median
external beam and BT doses were 45 and 25 Gy in four to five fractions. With 15
month median followup, the 2-year actuarial local control and overall survival
were 90.6% and 94.4%. No Grade 2-5 late toxicities were observed. Mean CTV D90
EQD2 for BT alone and combined therapy was 48.6 +/- 5.6 and 72.4 +/- 6.0 Gy,
whereas mean GTV D90 EQD2 was 172.3 +/- 59.6 and 138.0 +/- 64.6 Gy. CONCLUSIONS:
Image-based BT is feasible for medically inoperable early stage endometrial
cancer with excellent early results. Despite low CTV doses, high doses delivered
to GTV with BT likely accounts for high local control. Endometrial cancer
guidelines for image-based planning are needed to define target volumes based on
risk with differential dose delivery.
PMID- 25127123
TI - Permanent prostate brachytherapy with or without supplemental external beam
radiotherapy as practiced in Japan: outcomes of 1300 patients.
AB - PURPOSE: To report outcomes for men treated with iodine-125 ((125)I) prostate
brachytherapy (BT) at a single institution in Japan. METHODS AND MATERIALS:
Between 2003 and 2009, 1313 patients (median age, 68 years) with clinically
localized prostate cancer were treated with (125)I BT. Median prostate-specific
antigen level was 7.6 ng/mL (range, 1.1-43.3). T-stage was T1c in 60%, T2 in 39%,
and T3 in 1% of patients. The Gleason score was <7, 7, and >7 in 49%, 45%, and 6%
of patients, respectively. Neoadjuvant androgen deprivation therapy was used in
40% of patients and combined external beam radiotherapy of 45 Gy in 48% of
patients. Postimplant dosimetry was performed after 30 days after implantation,
with total doses converted to the biologically effective dose. Survival functions
were calculated by the Kaplan-Meier method and Cox hazard model. RESULTS: Median
followup was 67 months (range, 6-126). The 7-year biochemical freedom from
failure for low-, intermediate-, and selected high-risk prostate cancers were
98%, 93%, and 81%, respectively (p < 0.001). Multivariate analysis identified the
Gleason score, initial prostate-specific antigen level, positive biopsy rate,
dose, and neoadjuvant androgen deprivation therapy as predictors for biochemical
freedom from failure. The 7-year actuarial developing Grade 3+ genitourinary and
gastrointestinal toxicity was 2% and 0.3%, respectively. Forty-four percent
patients with normal baseline potency retained normal erectile function at 5
years. CONCLUSIONS: (125)I prostate BT is a highly effective treatment option for
low-, intermediate-, and selected high-risk prostate cancers. Side effects were
tolerable. An adequate dose may be required to achieve successful biochemical
control.
PMID- 25127124
TI - Development and implementation of a clinical needs assessment to support nursing
and midwifery students with a disability in clinical practice: part 1.
AB - Equality and disability legislation, coupled with increasing numbers of students
with a disability, and inadequate supports in clinical practice, acted as
catalysts to explore how best to support undergraduate nursing and midwifery
students on clinical placements. Historically, higher education institutions
provide reasonable accommodations for theoretical rather than clinical modules
for practice placements. This paper describes the development and implementation
of a Clinical Needs Assessment designed to identify the necessary supports or
reasonable accommodations for nursing and midwifery students with a disability
undertaking work placements in clinical practice. The existing literature, and
consultation with an expert panel, revealed that needs assessments should be
competency based and clearly identify the core skills or elements of practice
that the student must attain to achieve proficiency and competence. The five
Domains of Competence, advocated by An Bord Altranais, the Nursing and Midwifery
Board of Ireland, formed the framework for the Clinical Needs Assessment. A panel
of experts generated performance indicators to enable the identification of
individualised reasonable accommodations for year 1 nursing and midwifery
students in one Irish University. Development and implementation of the Clinical
Needs Assessment promoted equality, inclusion and a level playing field for
nursing and midwifery students with a disability in clinical practice.
PMID- 25127127
TI - Reduction of hydrogen peroxide accumulation and toxicity by a catalase from
Mycoplasma iowae.
AB - Mycoplasma iowae is a well-established avian pathogen that can infect and damage
many sites throughout the body. One potential mediator of cellular damage by
mycoplasmas is the production of H2O2 via a glycerol catabolic pathway whose
genes are widespread amongst many mycoplasma species. Previous sequencing of M.
iowae serovar I strain 695 revealed the presence of not only genes for H2O2
production through glycerol catabolism but also the first documented mycoplasma
gene for catalase, which degrades H2O2. To test the activity of M. iowae catalase
in degrading H2O2, we studied catalase activity and H2O2 accumulation by both M.
iowae serovar K strain DK-CPA, whose genome we sequenced, and strains of the H2O2
producing species Mycoplasma gallisepticum engineered to produce M. iowae
catalase by transformation with the M. iowae putative catalase gene, katE. H2O2
mediated virulence by M. iowae serovar K and catalase-producing M. gallisepticum
transformants were also analyzed using a Caenorhabditis elegans toxicity assay,
which has never previously been used in conjunction with mycoplasmas. We found
that M. iowae katE encodes an active catalase that, when expressed in M.
gallisepticum, reduces both the amount of H2O2 produced and the amount of damage
to C. elegans in the presence of glycerol. Therefore, the correlation between the
presence of glycerol catabolism genes and the use of H2O2 as a virulence factor
by mycoplasmas might not be absolute.
PMID- 25127128
TI - Systemic RNAi delivery to the muscles of ROSA26 mice reduces lacZ expression.
AB - RNAi has potential for therapeutically downregulating the expression of
dominantly inherited genes in a variety of human genetic disorders. Here we used
the ROSA26 mouse, which constitutively expresses the bacterial lacZ gene in
tissues body wide, as a model to test the ability to downregulate gene expression
in striated muscles. Recombinant adeno-associated viral vectors (rAAVs) were
generated that express short hairpin RNAs (shRNAs) able to target the lacZ mRNA.
Systemic delivery of these rAAV6 vectors led to a decrease of beta-galactosidase
expression of 30-50-fold in the striated muscles of ROSA26 mice. However, high
doses of vectors expressing 21 nucleotide shRNA sequences were associated with
significant toxicity in both liver and cardiac muscle. This toxicity was reduced
in cardiac muscle using lower vector doses. Furthermore, improved knockdown in
the absence of toxicity was obtained by using a shorter (19 nucleotide) shRNA
guide sequence. These results support the possibility of using rAAV vectors to
deliver RNAi sequences systemically to treat dominantly inherited disorders of
striated muscle.
PMID- 25127126
TI - Smad4 regulates ureteral smooth muscle cell differentiation during mouse
embryogenesis.
AB - Proper formation of ureteral smooth muscle cells (SMCs) during embryogenesis is
essential for ureter peristalsis that propels urine from the kidney to the
bladder in mammals. Currently the molecular factors that regulate differentiation
of ureteral mesenchymal cells into SMCs are incompletely understood. A recent
study has reported that Smad4 deficiency reduces the number of ureteral SMCs.
However, its precise role in the ureteral smooth muscle development remains
largely unknown. Here, we used Tbx18:Cre knock-in mouse line to delete Smad4 to
examine its requirement in the development of ureteral mesenchyme and SMC
differentiation. We found that mice with specific deletion of Smad4 in Tbx18
expressing ureteral mesenchyme exhibited hydroureter and hydronephrosis at
embryonic day (E) 16.5, and the mutant mesenchymal cells failed to differentiate
into SMCs with increased apoptosis and decreased proliferation. Molecular markers
for SMCs including alpha smooth muscle actin (alpha-SMA) and smooth muscle myosin
heavy chain (SM-MHC) were absent in the mutant ureters. Moreover, disruption of
Smad4 significantly reduced the expression of genes, including Sox9, Tbx18 and
Myocardin associated with SMC differentiation. These findings suggest that Smad4
is essential for initiating the SMC differentiation program during ureter
development.
PMID- 25127129
TI - Graph-based inter-subject pattern analysis of FMRI data.
AB - In brain imaging, solving learning problems in multi-subjects settings is
difficult because of the differences that exist across individuals. Here we
introduce a novel classification framework based on group-invariant graphical
representations, allowing to overcome the inter-subject variability present in
functional magnetic resonance imaging (fMRI) data and to perform multivariate
pattern analysis across subjects. Our contribution is twofold: first, we propose
an unsupervised representation learning scheme that encodes all relevant
characteristics of distributed fMRI patterns into attributed graphs; second, we
introduce a custom-designed graph kernel that exploits all these characteristics
and makes it possible to perform supervised learning (here, classification)
directly in graph space. The well-foundedness of our technique and the robustness
of the performance to the parameter setting are demonstrated through inter
subject classification experiments conducted on both artificial data and a real
fMRI experiment aimed at characterizing local cortical representations. Our
results show that our framework produces accurate inter-subject predictions and
that it outperforms a wide range of state-of-the-art vector- and parcel-based
classification methods. Moreover, the genericity of our method makes it is easily
adaptable to a wide range of potential applications. The dataset used in this
study and an implementation of our framework are available at
http://dx.doi.org/10.6084/m9.figshare.1086317.
PMID- 25127130
TI - An engineered factor Va prevents bleeding induced by anticoagulant wt activated
protein C.
AB - OBJECTIVE: An increased risk of bleeding is observed in patients receiving
activated protein C (APC), which may be a limiting factor for the application of
novel APC therapies. Since APC's therapeutic effects often require its
cytoprotective activities on cells but not APC's anticoagulant activities, an
agent that specifically antagonizes APC's anticoagulant effects but not its
cytoprotective effects could provide an effective means to control concerns for
risk of bleeding. We hypothesized that superFVa, an engineered activated FVa
variant that restores hemostasis in hemophilia could reduce APC-induced bleeding.
APPROACH AND RESULTS: SuperFVa was engineered with mutations of the APC cleavage
sites (Arg506/306/679Gln) and a disulfide bond (Cys609-Cys1691) between the A2
and A3 domains, which augment its biological activity and cause high resistance
to APC. SuperFVa normalized APC-prolonged clotting times and restored APC
suppressed thrombin generation in human and murine plasma at concentrations where
wild-type (wt) FVa did not show effects. Following intravenous injection of APC
into BALB/c mice, addition to whole blood ex vivo of superFVa but not wt-FVa
significantly normalized whole blood clotting. Blood loss following tail clip or
liver laceration was significantly reduced when superFVa was administered
intravenously to BALB/c mice prior to intravenous APC-treatment. Furthermore,
superFVa abolished mortality (~50%) associated with excessive bleeding following
liver laceration in mice treated with APC. CONCLUSIONS: Our results provide proof
of concept that superFVa is effective in preventing APC-induced bleeding and may
provide therapeutic benefits as a prohemostatic agent in various situations where
bleeding is a serious risk.
PMID- 25127131
TI - Birth weight reference percentiles for Chinese.
AB - OBJECTIVE: To develop a reference of population-based gestational age-specific
birth weight percentiles for contemporary Chinese. METHODS: Birth weight data was
collected by the China National Population-based Birth Defects Surveillance
System. A total of 1,105,214 live singleton births aged >=28 weeks of gestation
without birth defects during 2006-2010 were included. The lambda-mu-sigma method
was utilized to generate percentiles and curves. RESULTS: Gestational age
specific birth weight percentiles for male and female infants were constructed
separately. Significant differences were observed between the current reference
and other references developed for Chinese or non-Chinese infants. CONCLUSION:
There have been moderate increases in birth weight percentiles for Chinese
infants of both sexes and most gestational ages since 1980s, suggesting the
importance of utilizing an updated national reference for both clinical and
research purposes.
PMID- 25127132
TI - A novel compound NSC745885 exerts an anti-tumor effect on tongue cancer SAS cells
in vitro and in vivo.
AB - OBJECTIVE: Oral squamous cell carcinoma (OSCC) is a prevalent cancer, especially
in developing countries. Anthracyclines and their anthraquinone derivatives, such
as doxorubicin, exhibit a cell growth inhibitory effect and have been used as
anti-cancer drugs for many years. However, the cardiotoxicity of anthracycline
antibiotics is a major concern in their clinical application. NSC745885 is a
novel compound synthesized from 1,2-diaminoanthraquinone, which subsequently
reacts with thionyl chloride and triethylamine. The present study aimed to
investigate the anti-oral cancer potential and the safety of NSC745885. METHODS:
We investigated the anti-cancer potential of NSC745885 in oral squamous carcinoma
cell lines and in an in vivo oral cancer xenograft mouse model. The expression of
apoptotic related genes were evaluated by real-time RT-PCR and western bloting,
and the in vivo assessment of apoptotic marker were measured by
immunohistochemical staining. The anti-tumor efficiency and safety between
doxorubicin and NSC745885 were also compared. RESULTS: Our results demonstrated
that NSC745885 exhibits anti-oral cancer activity through the induction of
apoptosis in cancer cells and in tumor-bearing mice, and this treatment did not
induce marked toxicity in experimental mice. This compound also exhibits a
comparable anti-tumor efficiency and a higher safety in experimental mice when
compared to doxorubicin. CONCLUSIONS: The data of this study provide evidence for
NSC745885 as a potential novel therapeutic drug for the treatment of human OSCC.
PMID- 25127133
TI - Dietary regimens modify early onset of obesity in mice haploinsufficient for
Rai1.
AB - Smith-Magenis syndrome is a complex genomic disorder in which a majority of
individuals are obese by adolescence. While an interstitial deletion of
chromosome 17p11.2 is the leading cause, mutation or deletion of the RAI1 gene
alone results in most features of the disorder. Previous studies have shown that
heterozygous knockout of Rai1 results in an obese phenotype in mice and that
Smith-Magenis syndrome mouse models have a significantly reduced fecundity and an
altered transmission pattern of the mutant Rai1 allele, complicating large,
extended studies in these models. In this study, we show that breeding C57Bl/6J
Rai1+/- mice with FVB/NJ to create F1 Rai1+/- offspring in a mixed genetic
background ameliorates both fecundity and Rai1 allele transmission phenotypes.
These findings suggest that the mixed background provides a more robust platform
for breeding and larger phenotypic studies. We also characterized the effect of
dietary intake on Rai1+/- mouse growth during adolescent and early adulthood
developmental stages. Animals fed a high carbohydrate or a high fat diet gained
weight at a significantly faster rate than their wild type littermates. Both high
fat and high carbohydrate fed Rai1+/- mice also had an increase in body fat and
altered fat distribution patterns. Interestingly, Rai1+/- mice fed different
diets did not display altered fasting blood glucose levels. These results suggest
that dietary regimens are extremely important for individuals with Smith-Magenis
syndrome and that food high in fat and carbohydrates may exacerbate obesity
outcomes.
PMID- 25127134
TI - Modifying lipid rafts promotes regeneration and functional recovery.
AB - Ideal strategies to ameliorate CNS damage should promote both neuronal survival
and axon regeneration. The receptor Neogenin promotes neuronal apoptosis. Its
ligand prevents death, but the resulting repulsive guidance molecule a (RGMa)
Neogenin interaction also inhibits axonal growth, countering any prosurvival
benefits. Here, we explore strategies to inhibit Neogenin, thus simultaneously
enhancing survival and regeneration. We show that bone morphogenetic protein
(BMP) and RGMa-dependent recruitment of Neogenin into lipid rafts requires an
interaction between RGMa and Neogenin subdomains. RGMa or Neogenin peptides that
prevent this interaction, BMP inhibition by Noggin, or reduction of membrane
cholesterol all block Neogenin raft localization, promote axon outgrowth, and
prevent neuronal apoptosis. Blocking Neogenin raft association influences axonal
pathfinding, enhances survival in the developing CNS, and promotes survival and
regeneration in the injured adult optic nerve and spinal cord. Moreover, lowering
cholesterol disrupts rafts and restores locomotor function after spinal cord
injury. These data reveal a unified strategy to promote both survival and
regeneration in the CNS.
PMID- 25127135
TI - Single-cell imaging of caspase-1 dynamics reveals an all-or-none inflammasome
signaling response.
AB - Inflammasome-mediated caspase-1 activation is involved in cell death and the
secretion of the proinflammatory cytokine interleukin-1beta (IL-1beta). Although
the dynamics of caspase-1 activation, IL-1beta secretion, and cell death have
been examined with bulk assays in population-level studies, they remain poorly
understood at the single-cell level. In this study, we conducted single-cell
imaging using a genetic fluorescence resonance energy transfer sensor that
detects caspase-1 activation. We determined that caspase-1 exhibits all-or-none
(digital) activation at the single-cell level, with similar activation kinetics
irrespective of the type of inflammasome or the intensity of the stimulus. Real
time concurrent detection of caspase-1 activation and IL-1beta release
demonstrated that dead macrophages containing activated caspase-1 release a local
burst of IL-1beta in a digital manner, which identified these macrophages as the
main source of IL-1beta within cell populations. Our results highlight the value
of single-cell analysis in enhancing understanding of the inflammasome system and
chronic inflammatory diseases.
PMID- 25127136
TI - A pseudouridine residue in the spliceosome core is part of the filamentous growth
program in yeast.
AB - Although pseudouridine nucleobases are abundant in tRNAs, rRNAs, and small
nuclear RNAs (snRNAs), they are not known to have physiologic roles in cell
differentiation. We have identified a pseudouridine residue (Psi28) on
spliceosomal U6 snRNA that is induced during filamentous growth of Saccharomyces
cerevisiae. Pus1p catalyzes this modification and is upregulated during
filamentation. Several U6 snRNA mutants are strongly pseudouridylated at Psi28.
Remarkably, these U6 mutants activate pseudohyphal growth, dependent upon Pus1p,
arguing that U6-Psi28 per se can initiate at least part of the filamentous growth
program. We confirmed this by using a designer small nucleolar RNA (snoRNA)
targeting U6-U28 pseudouridylation. Conversely, mutants that block U6-U28
pseudouridylation inhibit pseudohyphal growth. U6-U28 pseudouridylation changes
the splicing efficiency of suboptimal introns; thus, Pus1p-dependent
pseudouridylation of U6 snRNA contributes to the filamentation growth program.
PMID- 25127137
TI - Gli3 repressor controls cell fates and cell adhesion for proper establishment of
neurogenic niche.
AB - Neural stem cells (NSCs) in the subventricular zone (SVZ) rely on environmental
signals provided by the neurogenic niche for their proper function. However,
little is known about the initial steps of niche establishment, as embryonic
radial glia transition to postnatal NSCs. Here, we identify Gli3 repressor
(Gli3R), a component of the Sonic hedgehog (Shh) pathway, as a critical factor
controlling both cell-type specification and structural organization of the
developing SVZ. We demonstrate that Gli3R expressed in radial glia temporally
regulates gp130/STAT3 signaling at the transcriptional level to suppress glial
characteristics in differentiating ependymal cells. In addition, Gli3R maintains
the proper level of Numb in ependymal cells to allow localization of cell
adhesion molecules such as vascular cell adhesion molecule (VCAM) and E-cadherin.
Thus, our findings reveal a role for Gli3R as a mediator of niche establishment
and provide insights into the conditions required for proper SVZ neurogenic niche
formation.
PMID- 25127138
TI - Costs and benefits of mutational robustness in RNA viruses.
AB - The accumulation of mutations in RNA viruses is thought to facilitate rapid
adaptation to changes in the environment. However, most mutations have
deleterious effects on fitness, especially for viruses. Thus, tolerance to
mutations should determine the nature and extent of genetic diversity that can be
maintained in the population. Here, we combine population genetics theory,
computer simulation, and experimental evolution to examine the advantages and
disadvantages of tolerance to mutations, also known as mutational robustness. We
find that mutational robustness increases neutral diversity and, as expected, can
facilitate adaptation to a new environment. Surprisingly, under certain
conditions, robustness may also be an impediment for viral adaptation, if a
highly diverse population contains a large proportion of previously neutral
mutations that are deleterious in the new environment. These findings may inform
therapeutic strategies that cause extinction of otherwise robust viral
populations.
PMID- 25127140
TI - Global scaling down of excitatory postsynaptic responses in cerebellar Purkinje
cells impairs developmental synapse elimination.
AB - Synapse elimination is crucial for precise neural circuit formation during
postnatal development. We examined how relative differences in synaptic strengths
among competing inputs and/or absolute synaptic strengths contribute to climbing
fiber (CF) to Purkinje cell (PC) synapse elimination in the cerebellum. We
generated mice with PC-selective deletion of stargazin (TARP gamma-2), the major
AMPA receptor auxiliary subunit in PCs (gamma-2 PC-KO mice). Whereas relative
differences between "strong" and "weak" CF-mediated postsynaptic response are
preserved, absolute strengths of CF inputs are scaled down globally in PCs of
gamma-2 PC-KO mice. Although the early phase of CF elimination is normal,
dendritic translocation of the strongest CF and the late phase of CF elimination
that requires Ca(2+)-dependent activation of Arc/Arg3.1 in PCs are both impaired
in gamma-2 PC-KO mice. We conclude that, although relative differences in CF
synaptic inputs are initially essential, proper synaptic scaling is crucial for
accomplishing CF synapse elimination.
PMID- 25127139
TI - Oncogene mimicry as a mechanism of primary resistance to BRAF inhibitors.
AB - Despite the development of potent RAF/mitogen-activated protein kinase (MAPK)
pathway inhibitors, only a fraction of BRAF-mutant patients benefit from
treatment with these drugs. Using a combined chemogenomics and chemoproteomics
approach, we identify drug-induced RAS-RAF-MEK complex formation in a subset of
BRAF-mutant cancer cells characterized by primary resistance to vemurafenib. In
these cells, autocrine interleukin-6 (IL-6) secretion may contribute to the
primary resistance phenotype via induction of JAK/STAT3 and MAPK signaling. In a
subset of cell lines, combined IL-6/MAPK inhibition is able to overcome primary
resistance to BRAF-targeted therapy. Overall, we show that the signaling
plasticity exerted by primary resistant BRAF-mutant cells is achieved by their
ability to mimic signaling features of oncogenic RAS, a strategy that we term
"oncogene mimicry." This model may guide future strategies for overcoming primary
resistance observed in these tumors.
PMID- 25127141
TI - Escape from telomere-driven crisis is DNA ligase III dependent.
AB - Short dysfunctional telomeres are capable of fusion, generating dicentric
chromosomes and initiating breakage-fusion-bridge cycles. Cells that escape the
ensuing cellular crisis exhibit large-scale genomic rearrangements that drive
clonal evolution and malignant progression. We demonstrate that there is an
absolute requirement for fully functional DNA ligase III (LIG3), but not ligase
IV (LIG4), to facilitate the escape from a telomere-driven crisis. LIG3- and LIG4
dependent alternative (A) and classical (C) nonhomologous end-joining (NHEJ)
pathways were capable of mediating the fusion of short dysfunctional telomeres,
both displaying characteristic patterns of microhomology and deletion. Cells that
failed to escape crisis exhibited increased proportions of C-NHEJ-mediated
interchromosomal fusions, whereas those that escaped displayed increased
proportions of intrachromosomal fusions. We propose that the balance between
inter- and intrachromosomal telomere fusions dictates the ability of human cells
to escape crisis and is influenced by the relative activities of A- and C-NHEJ at
short dysfunctional telomeres.
PMID- 25127142
TI - Balanced activity of three mitotic motors is required for bipolar spindle
assembly and chromosome segregation.
AB - Bipolar spindle assembly requires force to organize the microtubule network.
Here, we show that three motor proteins, namely Eg5, Kif15, and dynein, act
together to produce the right force balance in the spindle. Excessive inward
force results in monopolar spindle formation, while excessive outward force
generation results in unstable spindles with splayed spindle poles. Blocking
activity of all three motors prevents bipolar spindle formation, but established
bipolar spindles are refractory to loss of all motor activity. Further analysis
shows that although these preformed spindles remain bipolar, outward force
generation is required to establish sufficient tension on kinetochores and to
accomplish successful chromosome segregation. Together, these results show how
Eg5, Kif15, and dynein work together to build a bipolar spindle and reveal an
important role for antagonistic motors in chromosome segregation.
PMID- 25127144
TI - Sox6 and Otx2 control the specification of substantia nigra and ventral tegmental
area dopamine neurons.
AB - Distinct midbrain dopamine (mDA) neuron subtypes are found in the substantia
nigra pars compacta (SNc) and the ventral tegmental area (VTA), but it is mainly
SNc neurons that degenerate in Parkinson's disease. Interest in how mDA neurons
develop has been stimulated by the potential use of stem cells in therapy or
disease modeling. However, very little is known about how specific dopaminergic
subtypes are generated. Here, we show that the expression profiles of the
transcription factors Sox6, Otx2, and Nolz1 define subpopulations of mDA neurons
already at the neural progenitor cell stage. After cell-cycle exit, Sox6
selectively localizes to SNc neurons, while Otx2 and Nolz1 are expressed in a
subset of VTA neurons. Importantly, Sox6 ablation leads to decreased expression
of SNc markers and a corresponding increase in VTA markers, while Otx2 ablation
has the opposite effect. Moreover, deletion of Sox6 affects striatal innervation
and dopamine levels. We also find reduced Sox6 levels in Parkinson's disease
patients. These findings identify Sox6 as a determinant of SNc neuron development
and should facilitate the engineering of relevant mDA neurons for cell therapy
and disease modeling.
PMID- 25127145
TI - Sex-dependent gene expression in human pluripotent stem cells.
AB - Males and females have a variety of sexually dimorphic traits, most of which
result from hormonal differences. However, differences between male and female
embryos initiate very early in development, before hormonal influence begins,
suggesting the presence of genetically driven sexual dimorphisms. By comparing
the gene expression profiles of male and X-inactivated female human pluripotent
stem cells, we detected Y-chromosome-driven effects. We discovered that the sex
determining gene SRY is expressed in human male pluripotent stem cells and is
induced by reprogramming. In addition, we detected more than 200 differentially
expressed autosomal genes in male and female embryonic stem cells. Some of these
genes are involved in steroid metabolism pathways and lead to sex-dependent
differentiation in response to the estrogen precursor estrone. Thus, we propose
that the presence of the Y chromosome and specifically SRY may drive sex-specific
differences in the growth and differentiation of pluripotent stem cells.
PMID- 25127143
TI - Quantification of crypt and stem cell evolution in the normal and neoplastic
human colon.
AB - Human intestinal stem cell and crypt dynamics remain poorly characterized because
transgenic lineage-tracing methods are impractical in humans. Here, we have
circumvented this problem by quantitatively using somatic mtDNA mutations to
trace clonal lineages. By analyzing clonal imprints on the walls of colonic
crypts, we show that human intestinal stem cells conform to one-dimensional
neutral drift dynamics with a "functional" stem cell number of five to six in
both normal patients and individuals with familial adenomatous polyposis
(germline APC(-/+)). Furthermore, we show that, in adenomatous crypts (APC(-/-)),
there is a proportionate increase in both functional stem cell number and the
loss/replacement rate. Finally, by analyzing fields of mtDNA mutant crypts, we
show that a normal colon crypt divides around once every 30-40 years, and the
division rate is increased in adenomas by at least an order of magnitude. These
data provide in vivo quantification of human intestinal stem cell and crypt
dynamics.
PMID- 25127146
TI - Creation of a computer self-efficacy measure: analysis of internal consistency,
psychometric properties, and validity.
AB - Computer self-efficacy is an often studied construct that has been shown to be
related to an array of important individual outcomes. Unfortunately, existing
measures of computer self-efficacy suffer from several deficiencies, including
criterion contamination, outdated wording, and/or inadequate psychometric
properties. For this reason, the current article presents the creation of a new
computer self-efficacy measure. In Study 1, an over-representative item list is
created and subsequently reduced through exploratory factor analysis to create an
initial measure, and the discriminant validity of this initial measure is tested.
In Study 2, the unidimensional factor structure of the initial measure is
supported through confirmatory factor analysis and further reduced into a final,
12-item measure. In Study 3, the convergent and criterion validity of the 12-item
measure is tested. Overall, this three study process demonstrates that the new
computer self-efficacy measure has superb psychometric properties and internal
reliability, and demonstrates excellent evidence for several aspects of validity.
It is hoped that the 12-item computer self-efficacy measure will be utilized in
future research on computer self-efficacy, which is discussed in the current
article.
PMID- 25127147
TI - Triazolopyrimidine compounds containing first-row transition metals and their
activity against the neglected infectious Chagas disease and leishmaniasis.
AB - Leishmaniasis and Chagas disease remain a significant global problem. Current
treatments have serious disadvantage due to cost, toxicity, long therapy duration
and resistance. In the last years increasing interest has arisen in drug
development to fight both diseases. Recently, metal-based drugs have revealed as
promising drugs in a variety of therapeutic areas. Herein we describe six newly
synthesized transition metal complexes with a bioactive molecule 5,7-dimethyl
1,2,4-triazolo[1,5-a]pyrimidine (dmtp). All of them have been characterized by X
ray, spectroscopic and thermal methods. In vitro and in vivo studies (murine
model) on the antiproliferative activity of these complexes against Leishmania
spp. (Leishmania infantum, Leishmania braziliensis) and Trypanosoma cruzi have
been carried out. Our results reveal a strong potential of three of the assayed
compounds as antiparasitic agents against the above-mentioned infectious
diseases.
PMID- 25127148
TI - Some molecular targets for antihyperlipidemic drug research.
AB - High levels of cholesterol and other lipid constituents are major risk factors in
the development of atherosclerosis as well as diseases and disorders associated
with it. Though, drugs of various categories acting through different mechanisms
are available for antihyperlipidemic therapy, there are limitations associated
with each of them, keeping the interest in discovery of newer and better
antihyperlipidemic drugs alive. Identification and exploitation of novel
molecular targets for discovery of new antihyperlipidemic drugs is an important
area of research. Twenty such drug targets are elaborated herein, for their
biochemical roles, structures, estimations, as well as, exploitation for new drug
discovery research. Few recently discovered drugs are based on such molecular
targets are also discussed.
PMID- 25127149
TI - Synthesis and biological evaluation of 1alpha,25-dihydroxyvitamin D3 analogues
with aromatic side chains attached at C-17.
AB - Two new analogues of the steroid hormone 1alpha,25-dihydroxyvitamin D3 with
aromatic side chains attached at C-17 were designed to investigate their effects
on VDR, HL-60 cell differentiation and tumor cell proliferation. These analogues
were prepared by the classical photochemical ring opening approach. After the
protection of both the 1alpha- and 3beta-hydroxyl in 1alpha
hydroxydehydroepiandrosterone with TBS groups, followed by bromination with NBS
and debromination in the presence of gamma-collidine, the diene intermediate was
obtained. Hydrazone formation followed by iodine oxidation gave a vinyl iodide.
The aromatic side chain at C-17 was introduced via the Negishi coupling of the
resulting intermediate with an in situ generated zinc reagent with the
substituted aryl bromide (CD-side chain) in the presence of catalytic amount of
Pd(PPh3)4. After the removal of the TBDMS and MOM protective groups, followed by
UV irradiation and the subsequent thermal reaction, the 1alpha,25-(OH)2-D3
analogues with a substituted phenyl ring attached at C-17 to replace the C-20 and
C-21 were prepared. In the VDR competitive binding assay, compounds 2 and 3
almost lost their binding ability, and were only 0.01% and 0.015% as potent as
the 1alpha,25-dihydroxyvitamin D3. However, compounds 2 and 3 were as potent as
1alpha,25-(OH)2-D3 in inducing HL-60 cell differentiation at concentrations of
30, 100, 300, 1000 nM, respectively. Moreover, compounds 2 and 3 exhibited
similar or better antiproliferative potency against MCF-7 human breast cancer
cells, the IC50 values for analogues 2, 3 and the natural hormone were 7.08,
7.56, and 12.5 MUM, respectively.
PMID- 25127150
TI - Synthesis and in vitro antitumor activity of new series of benzothiazole and
pyrimido[2,1-b]benzothiazole derivatives.
AB - New series of benzothiazole and pyrimido[2,1-b]benzothiazole derivatives were
synthesized and characterized by analytical and spectrometrical methods (IR,
HRMS, (1)H and (13)C NMR). Nineteen of the synthesized compounds were selected by
the National Cancer Institute (NCI), USA, to be screened for their antitumor
activity at a single dose (10 MUM) against a panel of 60 cancer cell lines. The
most active compounds, 4, 6, 10, 14, 17 and 20 were selected for further
evaluation at five dose level screening. Compounds 17 (GI50 = 0.44 MUM, TGI = 1.2
MUM and LC50 MG-MID = 6.6 MUM) and 4 (GI50 = 0.77 MUM, TGI = 2.08 MUM and LC50 MG
MID = 11.74 MUM) were proved to be the most active members in this study. 3D and
2D pharmacophoric maps for the structural features of both compounds were
studied.
PMID- 25127151
TI - Extending the N-linked aminopiperidine class to the mycobacterial gyrase domain:
pharmacophore mapping from known antibacterial leads.
AB - Bacterial DNA gyrase is a well-established and clinically validated target to
develop novel antibacterial. Our effort was designated to search for
synthetically better compounds with possibility of hit to lead development. With
this as objective, a series of 1-(2-(4-aminopiperidin-1-yl)ethyl)-1,5
naphthyridin-2(1H)-one derivatives were designed by molecular hybridization
strategy and synthesized following nine step reaction to yield activity in low
nanomolar range and commendable antibacterial activities. Compound 1-(4
fluorophenyl)-3-(1-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin
4-yl)urea (35) emerged as the most promising inhibitor with an IC50 of 78 nM
against Mycobacterium tuberculosis DNA gyrase enzyme, with MTB MIC of 0.62 MUM,
and not cytotoxic at 50 MUM in eukaryotic cell line.
PMID- 25127152
TI - Novel multi-targeting anthra[2,3-b]thiophene-5,10-diones with guanidine
containing side chains: interaction with telomeric G-quadruplex, inhibition of
telomerase and topoisomerase I and cytotoxic properties.
AB - Novel generations of antitumor anthraquinones are expected to be advantageous
over the conventional chemotherapeutic agents. Previous structure-activity
relationship studies demonstrated an importance of the positively charged side
chains conjugated to anthra[2,3-b]thiophene-5,10-dione scaffolds. Exploring a
role of individual side chain moieties in binding to the duplex and G-quadruplex
DNA, modulation of telomerase and topoisomerase I activities, intracellular
accumulation and cytostatic potency, we herein analyzed a series of reported and
newly synthesized guanidine-containing derivatives of anthra[2,3-b]thiophene-5,10
dione. We found that the number of cationic side chains (namely, two) is critical
for a tight interaction with human telomeric G-quadruplex (TelQ). Along with a
larger drug-TelQ association constant, the telomerase attenuation by
anthrathiophenediones with two basic groups in the side chains was more
pronounced than by the analogs bearing one basic group. For mono-guanidinated
compounds the substituent with the amino group in the side chain provided better
TelQ affinity than the methylamine residue. The intracellular uptake of the mono
guanidino derivative with two side chains was >2-fold higher than the respective
value for the bis(guanidino) derivative. This difference can explain a lower
antiproliferative potency of bis(guanidine) containing compounds. Thus, the
modifications of side chains of anthra[2,3-b]thiophene-5,10-dione differently
modulated drug-target interactions and cellular effects. Nevertheless, the
selected compound 11-(3-aminopropylamino)-4-(2-guanidinoethylamino)anthra[2,3
b]thiophene-5,10-dione 13 demonstrated a high affinity to TelQ and the ability to
stabilize the quadruplex structure. These properties were paralleled by
reasonable potency of 13 as a telomerase/topoisomerase I inhibitor and an
antiproliferative agent. These results indicate that the structural elements of
anthra[2,3-b]thiophene-5,10-dione derivatives can be balanced to yield a
candidate for further preclinical study.
PMID- 25127153
TI - Synthesis of genistein coupled with sugar derivatives and their inhibitory effect
on nitric oxide production in macrophages.
AB - The isoflavone genistein 1 and some derivatives modulate IL-12, TNF-alpha and NO
production by macrophages and lung cancer cell lines, and improve the clinical
signs of experimental autoimmune encephalomyelitis (EAE). Seven genistein
derivatives connected at C-6 position of a sugar, such as d-glucose and d
galactose, were synthesized. The ability to modulate macrophage response was
evaluated, showing variable inhibition capacity of NO and TNF-alpha production in
J774.A1 and RAW 264.7. Five of the seven compounds were non-cytotoxic; compound 8
was more effective to inhibit NO and TNF-alpha production, without affecting cell
viability.
PMID- 25127155
TI - A case of secondary syphilis demonstrating nephrotic syndrome and a solitary
intrahepatic mass in a human immunodeficiency virus-1-infected patient.
AB - A 37-year-old, human immunodeficiency virus-1-infected Japanese man was referred
because of nephrotic syndrome following emergence of generalized skin rash.
Serological tests for syphilis turned out to be positive within ten months of the
referral. Abdominal echography incidentally revealed a solitary intrahepatic mass
without a detectable blood flow in segment 7. The patient's signs and symptoms,
as well as the intrahepatic mass, resolved promptly after administration of
amoxicillin. We consider that, in the present case, secondary syphilis caused the
nephrotic syndrome and the intrahepatic mass, both of which have rarely been
reported to date.
PMID- 25127154
TI - Novel thienopyrimidinones as mGluR1 antagonists.
AB - There has been much attention to discover mGluR1 antagonists for treating various
central nervous system diseases such as seizures and neuropathic pain.
Thienopyrimidinone derivatives were designed, synthesized, and biologically
evaluated against mGluR1. Among the synthesized compounds, 3-(4-methoxyphenyl)-7
(o-tolyl)thienopyrimidin-4-one 30 exhibited the most potent inhibitory activity
with an IC50 value of 45 nM and good selectivity over mGluR5. Also, the selective
mGluR1 antagonist 30 showed marginal hERG channel activity (IC50 = 9.87 MUM),
good profiles to CYP isozymes, and a good pharmacokinetic profile. Overall, the
compound 30 was identified as a selective mGluR1 antagonist with a good
pharmacokinetic profile, which is probably devoid of cardiac side effect and drug
drug interactions. Therefore, the compound 30 can be expected to be broadly used
as mGluR1 antagonistic chemical probe in in vitro and in vivo study for
investigating CNS diseases.
PMID- 25127156
TI - Fulminant pseudomembranous colitis caused by Clostridium difficile PCR ribotype
027 in a healthy young woman in Japan.
AB - In the past two decades, Clostridium difficile polymerase chain reaction ribotype
027 strain has rapidly emerged as the leading cause of antibiotic-associated
colitis in North America and Europe; however, it has been reported only
occasionally in Japan. We report a case of fulminant pseudomembranous colitis
caused by this strain in a healthy young woman in Japan without any previous
medical history. The strain isolated from our patient was susceptible to both
gatifloxacin and moxifloxacin, thus representing a historic strain. The
acquisition of fluoroquinolone resistance was reported as the important key
genetic event linked to the virulence of this strain. It is noteworthy that the
fluoroquinolone-susceptible 027 strain caused fulminant colitis in a healthy
young woman in a non-endemic area. Our experience suggests that C. difficile PCR
ribotype 027 has the potential virulence factors that are not associated with a
fluoroquinolone resistance-conferring mutation.
PMID- 25127157
TI - Sleep and exercise: a reciprocal issue?
AB - Sleep and exercise influence each other through complex, bilateral interactions
that involve multiple physiological and psychological pathways. Physical activity
is usually considered as beneficial in aiding sleep although this link may be
subject to multiple moderating factors such as sex, age, fitness level, sleep
quality and the characteristics of the exercise (intensity, duration, time of
day, environment). It is therefore vital to improve knowledge in fundamental
physiology in order to understand the benefits of exercise on the quantity and
quality of sleep in healthy subjects and patients. Conversely, sleep disturbances
could also impair a person's cognitive performance or their capacity for exercise
and increase the risk of exercise-induced injuries either during extreme and/or
prolonged exercise or during team sports. This review aims to describe the
reciprocal fundamental physiological effects linking sleep and exercise in order
to improve the pertinent use of exercise in sleep medicine and prevent sleep
disorders in sportsmen.
PMID- 25127158
TI - Co-infection with 'Candidatus Neoehrlichia mikurensis' and Borrelia afzelii in an
Ixodes ricinus tick that has bitten a human in Romania.
AB - Despite the vast importance of ticks as disease vectors, the infectious agents
transmitted by ticks are still incompletely known in many areas. Here, we report
for the first time the detection of the bacterium 'Candidatus Neoehrlichia
mikurensis' in Romania, in an Ixodes ricinus tick obtained from a human.
Furthermore, the tick also had a co-infection with Borrelia afzelii. 'Candidatus
Neoehrlichia mikurensis' is one of the most recent discoveries of a tick-borne
agent, and has been found in human patients in several European countries as well
as in China.
PMID- 25127159
TI - Highly sensitive method for diagnosis of subclinical B. ovis infection.
AB - Babesia ovis is a tick-transmitted protozoa parasite that infects small ruminants
causing fever, anaemia, hemoglobinuria, anorexia and, in acute cases, death.
Common in tropical and sub-tropical areas, the presence of this parasite in sheep
herds has an economic impact on industry and therefore sensitive methods for the
diagnosis and disease eradication are required. To achieve this goal, a semi
nested PCR for B. ovis specific identification was developed and consequent
reaction conditions and enzymes were optimized and tested with field samples. 300
blood samples from small ruminants and 39 ticks from Rhipicephalus genus were
collected from different regions of Portugal. Afterwards, DNA extraction was
performed and conventional and semi-nested PCR were accomplished for all samples.
The results obtained from both methodologies were compared and the sensitivity
was evaluated. Employing the semi-nested PCR it was possible to identify a higher
number of positive cases among the evaluated samples than using the conventional
PCR, namely 38/300 blood samples and 7/39 ticks. However, fragment amplification
was only observed in 5 out of 300 blood samples and in none of the 39 ticks when
a conventional PCR was employed. The validation of the results was achieved by
sequencing the DNA fragments corresponding to the hypervariable v4 region of the
18S ribosomal RNA gene and performing an alignment with sequences already
published on GenBank((r)). The ticks collected in this study belong to the
Rhipicephalus genus, although other species could be involved as a vector in the
Babesia spread. The diagnostic assay here described is presently the most
effective and sensitive method for detection of B. ovis in field blood samples
and ticks, enabling the detection up to 1 parasite into 10(9) erythrocytes.
PMID- 25127160
TI - Studies of Anaplasma phagocytophilum in sheep experimentally infected with the
human NY-18 isolate: characterization of tick feeding sites.
AB - Anaplasma phagocytophilum, transmitted by ticks of the genus Ixodes, was first
described in Scotland as the agent of tick-borne fever in sheep and more recently
as the cause of human granulocytic anaplasmosis in the U.S. and Europe. We
previously reported sheep as an experimental host for the human NY-18 isolate of
A. phagocytophilum. While clinical signs were not observed and infected
granulocytes were not seen in stained blood smears, these sheep served as a good
host for infection of ticks. In this research we characterized tick feeding sites
to better understand tick/host/pathogen interactions. Ixodes scapularis adults
were allowed to feed for 2 and 4 days on experimentally infected sheep, after
which biopsies were taken beneath tick feeding sites for histopathology, PCR and
immunohistochemistry (IHC) studies. In addition, the expression of selected
immune response genes was studied in blood and feeding site biopsies. While
necrosis was too advanced in 4-day biopsies for accurate cell counts, higher
numbers of eosinophils and neutrophils were found in 2-day biopsies from infected
sheep as compared with the uninfected controls. An unexpected result was the
documentation of higher dermal inflammation in infected sheep at sites without
ticks. A. phagocytophilum infected granulocytes were localized by
immunohistochemistry (IHC) in skin biopsies using rabbit antibodies against the
recombinant A. phagocytophilum major surface protein 4 as the primary antibody
for indirect peroxidase-anti-peroxidase and fluorescent antibody IHC. These
infected cells are likely to be the source of infection for ticks. Sheep
therefore served as good hosts for studying host/pathogen/tick interactions of
this human strain of A. phagocytophilum, and provided a means of producing
infected ticks for future studies on tick/pathogen developmental and transmission
cycles.
PMID- 25127161
TI - Occurrence of ticks and prevalence of Anaplasma phagocytophilum and Borrelia
burgdorferi s.l. in three types of urban biotopes: forests, parks and cemeteries.
AB - The aim of the present study was to compare different urban biotopes for the
occurrence of ixodid tick species, for the population density of Ixodes ricinus
and for the prevalence rates of two emerging, zoonotic pathogens. Altogether 2455
ticks were collected from the vegetation on 30 places (forests, parks,
cemeteries) of Budapest, Hungary. I. ricinus and Haemaphysalis concinna were
collected in all three biotope types, but Dermacentor reticulatus only in parks
and forests, and D. marginatus only in a forest. Highest population density of I.
ricinus was observed in neglected parts of cemeteries. In females of this tick
species the prevalence rates of Anaplasma phagocytophilum and Borrelia
burgdorferi s.l. were significantly lower in cemeteries, than in parks or
forests. In conclusion, risks associated with the presence of ticks and tick
borne pathogens may be high in a city, but this depends on biotope types, due to
habitat-related differences in the vegetation, as well as in the availability of
tick hosts and pathogen reservoirs.
PMID- 25127162
TI - Aqueous two-phase (PEG4000/Na2SO4) extraction and characterization of an acid
invertase from potato tuber (Solanum tuberosum).
AB - Invertases are key metabolic enzymes that catalyze irreversible hydrolysis of
sucrose into fructose and glucose. Plant invertases have essential roles in
carbohydrate metabolism, plant development, and stress responses. To study their
isolation and purification from potato, an attractive system useful for the
separation of biological molecules, an aqueous two-phase system, was used. The
influence of various system parameters such as type of phase-forming salts,
polyethylene glycol (PEG) molecular mass, salt, and polymer concentration was
investigated to obtain the highest recovery of enzyme. The PEG4000 (12.5%,
w/w)/Na2SO4(15%, w/w) system was found to be ideal for partitioning invertase
into the bottom salt-rich phase. The addition of 3% MnSO4 (w/w) at pH 5.0
increased the purity by 5.11-fold with the recovered activity of 197%. The Km and
Vmax on sucrose were 3.95 mM and 0.143 U mL(-1) min(-1), respectively. Our data
confirmed that the PEG4000/Na2SO4 aqueous two-phase system combined with the
presence of MnSO4 offers a low-cost purification of invertase from readily
available potato tuber in a single step. The biochemical characteristics of
temperature and pH stability for potato invertase prepared from an ATPS make the
enzyme a good candidate for its potential use in many research and industrial
applications.
PMID- 25127163
TI - Repurposing human PDE4 inhibitors for neglected tropical diseases: design,
synthesis and evaluation of cilomilast analogues as Trypanosoma brucei PDEB1
inhibitors.
AB - A medicinal chemistry exploration of the human phosphodiesterase 4 (hPDE4)
inhibitor cilomilast (1) was undertaken in order to identify inhibitors of
phosphodiesterase B1 of Trypanosoma brucei (TbrPDEB1). T. brucei is the parasite
which causes African sleeping sickness, a neglected tropical disease that affects
thousands each year, and TbrPDEB1 has been shown to be an essential target of
therapeutic relevance. Noting that 1 is a weak inhibitor of TbrPDEB1, we report
the design and synthesis of analogs of this compound, culminating in 12b, a sub
micromolar inhibitor of TbrPDEB1 that shows modest inhibition of T. brucei
proliferation.
PMID- 25127164
TI - Rupestonic acids B-G, NO inhibitory sesquiterpenoids from Artemisia rupestris.
AB - Six new guaiane sesquiterpenoids, rupestonic acids B-G (1-6), have been isolated
from the whole plants of Artemisia rupestris together with six known compounds (7
12). The structures of the new isolates (1-6) were elucidated on the basis of
extensive 1D and 2D NMR analysis, and the absolute configurations were
established by electronic circular dichroism (ECD) in combination with density
functional theory calculations. In in vitro bioassays, compounds 2 and 6
exhibited significant inhibitory effects on LPS-stimulated NO production in BV-2
microglial cells with IC50 values of 2.6 and 2.2 MUM, respectively.
PMID- 25127166
TI - Cryptochinones from Cryptocarya chinensis act as farnesoid X receptor agonists.
AB - Cryptochinones A-D are tetrahydroflavanones isolated from the leaves of
Cryptocarya chinensis, an evergreen tree whose extracts are believed to have a
variety of health benefits. The origin of their possible bioactivity is unclear.
The farnesoid X receptor (FXR) is a member of nuclear receptor superfamily that
has been widely targeted for developing treatments for chronic liver disease and
for hyperglycemia. We studied whether cryptochinones A-D, which are structurally
similar to known FXR ligands, may act at this target. Indeed, in mammalian one
hybrid and transient transfection reporter assays, cryptochinones A-D
transactivated FXR to modulate promoter action including GAL4, SHP, CYP7A1, and
PLTP promoters in dose-dependent manner, while they exhibited similar agonistic
activity as chenodeoxycholic acid (CDCA), an endogenous FXR agonist. Through
molecular modeling docking studies we evaluated their ability to bind to the FXR
ligand binding pocket. Our results indicate that cryptochinones A-D can behave as
FXR agonists.
PMID- 25127165
TI - A new phenylpropanoid and an alkylglycoside from Piper retrofractum leaves with
their antioxidant and alpha-glucosidase inhibitory activity.
AB - Two new compounds, piperoside (1) and isoheptanol 2(S)-O-beta-D-xylopyranosyl (1
>6)-O-beta-D-glucopyranoside (11), along with 10 known compounds 3,4
dihydroxyallylbenzene (2), 1,2-di-O-beta-D-glucopyranosyl-4-allylbenzene (3),
tachioside (4), benzyl-O-beta-D-glucopyranoside (5), icariside F2 (6),
dihydrovomifoliol-3'-O-beta-D-glucopyranoside (7), isopropyl O-beta-D
glucopyranoside (8), isopropyl primeveroside (9), n-butyl O-beta-D
glucopyranoside (10), isoheptanol 2(S)-O-beta-D-apiofuranosyl-(1->6)-O-beta-D
glucopyranoside (12), were isolated from the leaves of Piper retrofractum. Their
structures were determined from 1D-NMR, 2D-NMR, and HR-ESI-MS spectral, a
modified Mosher's method, and comparisons with previous reports. All of the
isolated compounds showed modest alpha-glucosidase inhibitory (4.60+/-1.74% to
11.97+/-3.30%) and antioxidant activities under the tested conditions.
PMID- 25127167
TI - New class of methyl tetrazole based hybrid of (Z)-5-benzylidene-2-(piperazin-1
yl)thiazol-4(%H)-one as potent antitubercular agents.
AB - In search of potential therapeutics for tuberculosis, we describe here the
synthesis and in vitro antitubercular activity of a novel series of thiazolone
piperazine tetrazole derivatives. Among all the synthesized derivatives, four
compounds (10, 14, 20 and 33) exhibited more potent activity (MIC=3.08, 3.01,
2.62 and 2.51 MUM) than ethambutol (MIC=9.78 MUM) and pyrazinamide (MIC=101.53
MUM) against Mycobacterium tuberculosis. Furthermore, they displayed no toxicity
against Vero cells (C1008) and mouse bone marrow derived macrophages (MBMDMphi).
These investigated analogues have emerged as possible lead molecule to enlarge
the scope of the study.
PMID- 25127168
TI - Comparison of saponin composition and content in wild soybean (Glycine soja Sieb.
and Zucc.) before and after germination.
AB - Eight wild soybean accessions with different saponin phenotypes were used to
examine saponin composition and relative saponin quantity in various tissues of
mature seeds and two-week-old seedlings by LC-PDA/MS/MS. Saponin composition and
content were varied according to tissues and accessions. The average total
saponin concentration in 1 g mature dry seeds of wild soybean was 16.08 +/- 3.13
MUmol. In two-week-old seedlings, produced from 1 g mature seeds, it was 27.94 +/
6.52 MUmol. Group A saponins were highly concentrated in seed hypocotyl (4.04 +/
0.71 MUmol). High concentration of DDMP saponins (7.37 +/- 5.22 MUmol) and Sg-6
saponins (2.19 +/- 0.59 MUmol) was found in cotyledonary leaf. In seedlings, the
amounts of group A and Sg-6 saponins reduced 2.3- and 1.3-folds, respectively,
while DDMP + B + E saponins increased 2.5-fold than those of mature seeds. Our
findings show that the group A and Sg-6 saponins in mature seeds were degraded
and/or translocated by germination whereas DDMP saponins were newly synthesized.
PMID- 25127169
TI - Biochemical characterization of two thermostable xylanolytic enzymes encoded by a
gene cluster of Caldicellulosiruptor owensensis.
AB - The xylanolytic extremely thermophilic bacterium Caldicellulosiruptor owensensis
provides a promising platform for xylan utilization. In the present study, two
novel xylanolytic enzymes, GH10 endo-beta-1,4-xylanase (Coxyn A) and GH39 beta
1,4-xylosidase (Coxyl A) encoded in one gene cluster of C.owensensis were
heterogeneously expressed and biochemically characterized. The optimum
temperature of the two xylanlytic enzymes was 75 degrees C, and the respective
optimum pH for Coxyn A and Coxyl A was 7.0 and 5.0. The difference of Coxyn A and
Coxyl A in solution was existing as monomer and homodimer respectively, it was
also observed in predicted secondary structure. Under optimum condition, the
catalytic efficiency (kcat/Km) of Coxyn A was 366 mg ml(-1) s(-1) on beechwood
xylan, and the catalytic efficiency (kcat/Km) of Coxyl A was 2253 mM(-1) s(-1) on
pNP-beta-D-xylopyranoside. Coxyn A degraded xylan to oligosaccharides, which were
converted to monomer by Coxyl A. The two intracellular enzymes might be
responsible for xylooligosaccharides utilization in C.owensensis, also provide a
potential way for xylan degradation in vitro.
PMID- 25127170
TI - Glycemic effect of oat and barley beta-glucan when incorporated into a snack bar:
a dose escalation study.
AB - BACKGROUND: The blood glucose-lowering effects of beta-glucan from oats and
barley depend on the amounts consumed and their rheological properties. This has
been recently challenged with growing evidence that the food matrix may also be
an important factor in predicting its physiological response. OBJECTIVE: The
objective of this study was to examine the effects of varying doses of beta
glucan from oats and barley and added to a snack bar on postprandial glycemia.
DESIGN: In a randomized crossover study, 12 healthy males and females consumed
one of 8 snack bars containing 0 (control), 1.5, 3, and 6 g of beta-glucan
derived from oats or barley or 3 white bread controls. All treatments contained
50 g of available carbohydrate. Blood glucose concentrations were measured after
ingestion of the treatments over 2 hours. RESULTS: Incorporation of 1.5 to 6 g of
beta-glucan into snack bars had no additional glucose-lowering benefits
irrespective of dose and source compared to the control bars (0 g beta-glucan),
suggesting that both the solid food matrix and composition of the bars may play a
role in their effects on glycemic response. All bars reduced blood glucose area
under the curve (AUC) by an average of 25% (p < 0.05) compared to the mean of the
3 white bread controls. CONCLUSION: Adding beta-glucan from oats and barley to
the snack bar formulation used in this study did not yield any additional
benefits beyond the glucose-lowering effects of the snack bars themselves.
PMID- 25127171
TI - Anti-CGRP antibodies: a new approach to migraine prevention.
PMID- 25127172
TI - Epilepsy: lost in translation.
PMID- 25127173
TI - Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene
related peptide, for the prevention of migraine: a phase 2, randomised, double
blind, placebo-controlled study.
AB - BACKGROUND: Migraine remains poorly treated, with few effective preventive drugs
available. We assessed the safety and efficacy of LY2951742, a fully humanised
monoclonal antibody to calcitonin gene-related peptide, for migraine prevention.
METHODS: We did a randomised, double-blind, placebo-controlled, phase 2 proof-of
concept study at 35 centres in the USA. Patients aged 18-65 years with four to 14
migraine headache days per month were randomly assigned (1:1) to LY2951742 or
placebo by a computerised randomisation scheme. LY2951742 (150 mg) or placebo
were given as a subcutaneous injection once every 2 weeks for 12 weeks. The
primary endpoint was the mean change in number of migraine headache days per 28
day period assessed at 9-12 weeks. Safety was assessed over 24 weeks, including
the 12-week treatment period and the subsequent 12 weeks after study drug
administration. Patients and treating investigators were masked to treatment
allocation. Analyses were by intention to treat. A mixed-effects model of
repeated measures was used, including patient baseline value, treatment, visit,
and treatment-by-visit interaction as fixed effects, and patients as random
effects. Safety measures were analysed according to the treatment received. This
study has been completed and is registered with ClinicalTrials.gov, NCT01625988.
FINDINGS: Between July 31, 2012, and Sept 18, 2013, 218 patients were randomly
assigned to LY2951742 (n=108, but one patient withdrew before treatment) or
placebo (n=110). The mean change from baseline to week 12 in the number of
migraine headache days was -4.2 (SD 3.1; 62.5% decrease) in the LY2951742 group
compared with -3.0 (SD 3.0; 42.3% decrease) in the placebo group (least-squares
mean difference -1.2, 90% CI -1.9 to -0.6; p=0.0030). Adverse events that
occurred more frequently with LY2951742 than with placebo included injection site
pain, erythema, or both (21 [20%] of 107 vs seven [6%] of 110), upper respiratory
tract infections (18 [17%] vs ten [9%]), and abdominal pain (six [6%] vs three
[3%]). There were two serious adverse events reported in the treatment arm and
four in the placebo arm, none of which were deemed to be related to the study
drug. INTERPRETATION: These results provide preliminary evidence that LY2951742
might be beneficial in migraine prevention and provide support for the role of
calcitonin gene-related peptide in the pathogenesis of migraine. Further
controlled studies are needed to assess the safety and efficacy of monoclonal
calcitonin gene-related peptide antibodies for the preventive treatment of
migraine. FUNDING: Arteaus Therapeutics.
PMID- 25127175
TI - Atorvastatin induces T cell proliferation by a telomerase reverse transcriptase
(TERT) mediated mechanism.
AB - Statins are one of the most potent drugs in delaying age-related inflammatory
changes in the arterial vessel wall, slowing down the progression of
atherosclerosis. Statins have also been shown to abrogate telomere-attributed
cardiovascular risk. The goal of our study was to explore a potential effect of
atorvastatin on telomerase activity in peripheral blood mononuclear cells (PBMCs)
and T-lymphocytes (T cells). METHODS AND RESULTS: Treatment with
pharmacologically relevant concentrations (0.1-0.3 MUM) of atorvastatin resulted
in a 6-fold increase of telomerase activity (TA) (p < 0.0001) in human and mouse
PBMCs and CD4 T cells, translating into moderate proliferation of T lymphocytes.
In contrast, high doses of atorvastatin (2-5 MUM) or the addition of LDL
cholesterol completely inhibited proliferation, thereby abrogating telomerase
activity. The proliferative effect of atorvastatin was ablated by the absense of
the catalytic subunit of telomerase, telomerase reverse transcriptase (TERT).
Using transgenic GFP-mTert reporter mice, we observed a decrease in telomerase
positive lymphocytes from 30% to 15% during the first 5 months of age (p < 0.01).
This suggests that the decrease in immune cell turnover during normal development
and maturation is mirrored by a reduction in telomerase activity in lymphocytes
in-vivo. CONCLUSION: Atorvastatin and cholesterol have opposing effects on
telomerase in mononuclear cells and T-lymphocytes. Our study suggests a link
between cholesterol metabolism and telomere-related cardiovascular risk.
PMID- 25127176
TI - Does "thinking about thinking" interfere with memory? An experimental memory
study in obsessive-compulsive disorder.
AB - Neuropsychological assessments of participants with obsessive-compulsive disorder
(OCD) indicate impaired verbal memory if to be remembered material has to be
organized. People with OCD also tend to focus their attention on their thoughts
(heightened cognitive self-consciousness). We tested the hypothesis that
cognitive self-consciousness causes verbal memory deficits by provoking a
division of attention between study task and thoughts. Thirty-six participants
with OCD, 36 matched healthy controls and 36 participants with major depressive
disorder (MDD) learned under proactive interference in three study conditions:
single-task condition, condition with heightened cognitive self-consciousness and
condition with an external secondary task. Memory was impaired in the cognitive
self-consciousness condition compared to both other conditions. Independent of
condition, participants with OCD showed a reduced memory performance compared to
healthy controls, but did not differ from participants with MDD. Our results are
in line with the hypothesis that cognitive self-consciousness causes memory
impairment.
PMID- 25127174
TI - The challenge and promise of anti-epileptic therapy development in animal models.
AB - Translation of successful target and compound validation studies into clinically
effective therapies is a major challenge, with potential for costly clinical
trial failures. This situation holds true for the epilepsies-complex diseases
with different causes and symptoms. Although the availability of predictive
animal models has led to the development of effective antiseizure therapies that
are routinely used in clinical practice, showing that translation can be
successful, several important unmet therapeutic needs still exist. Available
treatments do not fully control seizures in a third of patients with epilepsy,
and produce substantial side-effects. No treatment can prevent the development of
epilepsy in at-risk patients or cure patients with epilepsy. And no specific
treatment for epilepsy-associated comorbidities exists. To meet these demands, a
redesign of translational approaches is urgently needed.
PMID- 25127177
TI - Accelerate farmer's agricultural S&T training in Tibet.
PMID- 25127179
TI - ACT Internet-based vs face-to-face? A randomized controlled trial of two ways to
deliver Acceptance and Commitment Therapy for depressive symptoms: an 18-month
follow-up.
AB - The aim of the present study was to investigate two interventions based on
Acceptance and Commitment Therapy (ACT) for depressive symptoms: A face-to-face
treatment (ACT group) was compared to a guided self-help treatment delivered via
the Internet consisting of two assessment sessions (pre and post) and an ACT
based Internet program (iACT). Outpatients experiencing at least mild depressive
symptoms were randomized to either approach. The iACT treatment group received
access to an ACT-based Internet program and supportive web-based contact over a
period of 6 weeks. The face-to-face group received ACT-based treatment once a
week over the same period of time. In both groups, the results showed a
significant effect on depression symptomatology, and general wellbeing after
treatment and at the 18-month follow-up. However, the data indicated that the
iACT group changed differently regarding depressive symptoms and wellbeing as
compared to the face-to face ACT group. Results showed large pre-treatment to 18
month follow-up within-group effect sizes for all symptom measures in the iACT
treatment group (1.59-2.08), and for most outcome measures in the face-to-face
ACT group (1.12-1.37). This non-inferiority study provides evidence that guided
Internet-delivered ACT intervention can be as effective as ACT-based face-to-face
treatment for outpatients reporting depressive symptoms, and it may offer some
advantages over a face-to-face intervention.
PMID- 25127178
TI - Treatment of co-occurring PTSD-AUD: effects of exposure-based and non-trauma
focused psychotherapy on alcohol and trauma cue-reactivity.
AB - Laboratory studies have shown that exposure to trauma memories increases both
craving and salivation responses to alcohol cues among individual with co
occurring posttraumatic stress disorder (PTSD) and alcohol dependence (AD). The
purpose of the present study was to examine 1) whether this cue reactivity is
dampened following exposure-based treatment for PTSD and 2) how changes in
reactivity to trauma cues correspond to changes in alcohol cue-reactivity. Adults
with current PTSD and AD (N = 120) were randomly assigned to 9-12 sessions of
either Trauma-focused Exposure Therapy (EXP) for PTSD or Health & Lifestyles
(HLS, a non-trauma focused comparison treatment), concurrent with 6-week
residential AD treatment-as-usual. Participants completed trauma and alcohol cue
reactivity laboratory sessions before and after treatment. Compared to HLS,
individuals receiving EXP showed significantly greater reductions in negative
affect elicited by trauma cues following treatment. Both treatments demonstrated
similar, moderate to large reductions in craving and salivary reactivity over
time. Interestingly, latent change in trauma cue-elicited distress over the
course of treatment predicted latent change in both trauma cue-elicited alcohol
craving and salivation. Overall, findings highlight the utility of integrating
trauma-focused therapies like EXP into substance use treatment in the interests
of reducing PTSD symptoms and distress associated with trauma cues.
PMID- 25127181
TI - Laser-induced nondestructive patterning of a thin ferroelectric polymer film with
controlled crystals using Ge8Sb2Te11 alloy layer for nonvolatile memory.
AB - We present a simple but robust nondestructive process for fabricating
micropatterns of thin ferroelectric polymer films with controlled crystals. Our
method is based on utilization of localized heat arising from thin
Ge(8)Sb(2)Te(11) (GST) alloy layer upon exposure of 650 nm laser. The heat was
generated on GST layer within a few hundred of nanosecond exposure and
subsequently transferred to a thin poly(vinylidene fluoride-co-trifluoroethylene)
film deposited on GST layer. By controlling exposure time and power of the
scanned laser, ferroelectric patterns of one or two microns in size are
fabricated with various shape. In the micropatterned regions, ferroelectric
polymer crystals were efficiently controlled in both degree of the crystallinity
and the molecular orientations. Nonvolatile memory devices with laser scanned
ferroelectric polymer layers exhibited excellent device performance of large
remnant polarization, ON/OFF current ratio and data retention. The results are
comparable with devices containing ferroelectric films thermally annealed at
least for 2 h, making our process extremely efficient for saving time.
Furthermore, our approach can be conveniently combined with a number of other
functional organic materials for the future electronic applications.
PMID- 25127180
TI - Clinical application of inert gas Multiple Breath Washout in children and
adolescents with asthma.
AB - INTRODUCTION: Children with asthma often have normal spirometry despite
significant disease. The pathology of the small airways in asthma may be assessed
using Multiple Breath Washout (MBW) and calculating the Lung Clearance Index
(LCI). There are only few studies using MBW in children with asthma and existing
data regarding bronchodilator effect are contradictory. The aim of the present
pilot study was to compare LCI in asthma and controls and assess the effect of
salbutamol in children with asthma on the LCI. METHODS: Unselected patients with
a diagnosis of asthma visiting the outpatient department of our hospital between
04-2010 and 03-2011 were recruited and compared to a healthy control group. MBW
was performed as inert gas MBW using sulfurhexafluorid (SF6) as the tracer gas.
Clinical data were documented and spirometry and MBW (EasyOne Pro, MBW module,
NDD Switzerland) were performed before and after the use of salbutamol (200-400
MUg). Healthy controls performed baseline MBW only. RESULTS: 32 children
diagnosed with asthma (4.7-17.4 years) and 42 controls (5.3-20.8) were included
in the analysis. LCI differed between patients and controls, with a mean LCI (SD)
of 6.48 (0.48) and 6.21 (0.38) (P = 0.008). Use of salbutamol had no significant
effect on LCI for the group. CONCLUSION: These pilot data show that clinically
stable asthma patients and controls both have a LCI in the normal range. However,
in patients the LCI is significantly higher indicating that MBW may have a role
in assessing small airways disease in asthma.
PMID- 25127182
TI - Stormwater chemical contamination caused by cured-in-place pipe (CIPP)
infrastructure rehabilitation activities.
AB - Cured-in-place pipe (CIPP) is becoming a popular U.S. stormwater culvert
rehabilitation method. Several State transportation agencies have reported that
CIPP activities can release styrene into stormwater, but no other contaminants
have been monitored. CIPP's stormwater contamination potential and that of its
condensate waste was characterized. Condensate completely dissolved Daphnia magna
within 24 h. Condensate pH was 6.2 and its chemical oxygen demand (COD) level was
36,000 ppm. D. magna mortality (100%) occurred in 48 h, even when condensate was
diluted by a factor of 10,000 and styrene was present at a magnitude less than
its LC50. Condensate and stormwater contained numerous carcinogenic solvents used
in resin synthesis, endocrine disrupting contaminants such as plasticizers, and
initiator degradation products. For 35 days, COD levels at the culvert outlets
and downstream ranged from 100 to 375 ppm and styrene was 0.01 to 7.4 ppm.
Although contaminant levels generally reduced with time, styrene levels were
greatest 50 ft downstream, not at the culvert outlet. Cured CIPP extraction tests
confirmed that numerous contaminants other than styrene were released into the
environment and their persistence and toxicity should be investigated. More
effective contaminant containment and cleaner installation processes must be
developed to protect the environment.
PMID- 25127183
TI - Challenges and opportunities in epigenetic drug discovery.
PMID- 25127184
TI - Exploring the Concepts of Abstinence and Recovery Through the Experiences of Long
Term Opiate Substitution Clients.
AB - BACKGROUND: This study aimed to explore the client experience of long-term opiate
substitution treatment (OST). METHODS: A qualitative grounded theory study set in
a U.K. rural community drug treatment service. RESULTS: Continuous OST enabled
stability and a sense of "normality." Participants expressed relief at moving
away from previous chaotic lifestyles and freedom from the persistent fear of
opiate withdrawal. However, for some, being on a script made them feel withdrawn,
lethargic, and unable to fully participate in mainstream society. Intrapersonal
barriers (motivation and fear) were perceived as key barriers to abstinence.
CONCLUSIONS: Participants experienced long-term OST as a transition between
illicit drug use and recovery. Recovery was seen as a process rather than a fixed
goal, confirming that there is a need for services to negotiate individualized
recovery goals, spanning harm minimization and abstinence-oriented treatment
approaches.
PMID- 25127185
TI - Hydrogen bonding, halogen bonding and lithium bonding: an atoms in molecules and
natural bond orbital perspective towards conservation of total bond order, inter-
and intra-molecular bonding.
AB - One hundred complexes have been investigated exhibiting D-X...A interactions,
where X = H, Cl or Li and DX is the 'X bond' donor and A is the acceptor. The
optimized structures of all these complexes have been used to propose a
generalized 'Legon-Millen rule' for the angular geometry in all these
interactions. A detailed Atoms in Molecules (AIM) theoretical analysis confirms
an important conclusion, known in the literature: there is a strong correlation
between the electron density at the XA bond critical point (BCP) and the
interaction energy for all these interactions. In addition, we show that
extrapolation of the fitted line leads to the ionic bond for Li-bonding
(electrostatic) while for hydrogen and chlorine bonding, it leads to the covalent
bond. Further, we observe a strong correlation between the change in electron
density at the D-X BCP and that at the X...A BCP, suggesting conservation of the
bond order. The correlation found between penetration and electron density at BCP
can be very useful for crystal structure analysis, which relies on arbitrary van
der Waals radii for estimating penetration. Various criteria proposed for shared-
and closed-shell interactions based on electron density topology have been tested
for H/Cl/Li bonded complexes. Finally, using the natural bond orbital (NBO)
analysis it is shown that the D-X bond weakens upon X bond formation, whether it
is ionic (DLi) or covalent (DH/DCl) and the respective indices such as ionicity
or covalent bond order decrease. Clearly, one can think of conservation of bond
order that includes ionic and covalent contributions to both D-X and X...A bonds,
for not only X = H/Cl/Li investigated here but also any atom involved in
intermolecular bonding.
PMID- 25127187
TI - Radiation stability of cations in ionic liquids. 5. Task-specific ionic liquids
consisting of biocompatible cations and the puzzle of radiation hypersensitivity.
AB - In 1953, an accidental discovery by Melvin Calvin and co-workers provided the
first example of a solid (the alpha-polymorph of choline chloride) showing
hypersensitivity to ionizing radiation: under certain conditions, the radiolytic
yield of decomposition approached 5 * 10(4) per 100 eV (which is 4 orders of
magnitude greater than usual values), suggesting an uncommonly efficient
radiation-induced chain reaction. Twenty years later, the still-accepted
mechanism for this rare condition was suggested by Martyn Symons, but no
validation for this mechanism has been supplied. Meanwhile, ionic liquids and
deep eutectic mixtures that are based on choline, betainium, and other
derivitized natural amino compounds are presently finding an increasing number of
applications as diluents in nuclear separations, where the constituent ions are
exposed to ionizing radiation that is emitted by decaying radionuclides. Thus,
the systems that are compositionally similar to radiation hypersensitive solids
are being considered for use in high radiation fields, where this property is
particularly undesirable! In Part 5 of this series on organic cations, we revisit
the phenomenon of radiation hypersensitivity and explore mechanistic aspects of
radiation-induced reactions involving this class of task-specific, biocompatible,
functionalized cations, both in ionic liquids and in reference crystalline
compounds. We demonstrate that Symons' mechanism needs certain revisions and
rethinking, and suggest its modification. Our reconsideration suggests that there
cannot be conditions leading to hypersensitivity in ionic liquids.
PMID- 25127186
TI - Stereoconvergent arylations and alkenylations of unactivated alkyl electrophiles:
catalytic enantioselective synthesis of secondary sulfonamides and sulfones.
AB - The development of efficient methods for the generation of enantioenriched
sulfonamides and sulfones is an important objective for fields such as organic
synthesis and medicinal chemistry; however, there have been relatively few
reports of direct catalytic asymmetric approaches to controlling the
stereochemistry of the sulfur-bearing carbon of such targets. In this report, we
describe nickel-catalyzed stereoconvergent Negishi arylations and alkenylations
of racemic alpha-bromosulfonamides and -sulfones that furnish the desired cross
coupling product in very good ee and yield for an array of reaction partners.
Mechanistic studies are consistent with the generation of a radical intermediate
that has a sufficient lifetime to diffuse out of the solvent cage and to cyclize
onto a pendant olefin.
PMID- 25127188
TI - Optical functional performance of the osteo-odonto-keratoprosthesis.
AB - PURPOSE: The aim of this study was to evaluate optical and visual functional
performance of the osteo-odonto-keratoprosthesis (OOKP). METHODS: Optical design
and analysis was performed with customized optical design software. Nine patients
with implanted OOKP devices and 9 age-matched control patients were assessed.
Contrast sensitivity was assessed and glare effect was measured with a brightness
acuity test. All OOKP patients underwent kinetic Goldmann perimetry and wavefront
aberrometry and completed the National Eye Institute Visual Function
Questionnaire-25 (NEI VFQ-25). RESULTS: Optical analysis showed that the optical
cylinder is near diffraction-limited. A reduction in median visual acuity (VA)
with increasing glare settings was observed from 0.04 logMAR (without glare) to
0.20 logMAR (with glare at "high" setting) and significantly reduced
statistically when compared with the control group at all levels of glare (P <
0.05). Contrast sensitivity was significantly reduced when compared with age
matched controls at medium and high spatial frequencies (P < 0.05). Median
Goldmann perimetry was 65 degrees (interquartile range, 64-74 degrees; V-4e
isopters) and 69 degrees excluding 2 glaucomatous subjects. Several vision
related NEI VFQ-25 subscales correlated significantly with VA at various
brightness acuity test levels and contrast sensitivity at medium spatial
frequencies, including dependency, general vision, near activities and distance
activities. CONCLUSIONS: The OOKP optical cylinder provides patients with a good
level of VA that is significantly reduced by glare. We have shown in vivo that
updates to the optical cylinder design have improved the patient's field of view.
Reduction of glare and refinement of cylinder alignment methods may further
improve visual function and patient satisfaction.
PMID- 25127189
TI - New combined technique of deep intrastromal arcuate keratotomy overlayed by LASIK
flap for treatment of high astigmatism.
AB - PURPOSE: The aim of this study was to describe a novel technique combining deep
intrastromal arcuate keratotomy and superficial lamellar keratotomy followed by
excimer photoablation for the management of high naturally occurring or
postkeratoplasty astigmatism. METHODS: In this retrospective case series, the
first step was deep intrastromal arcuate keratotomy and superficial lamellar
keratotomy performed at 100-MUm depth by femtosecond laser. Manual incisions were
made for flap elevation. The second step, after 1 month, consisted of reopening
the flap and using an excimer laser to correct residual ametropia. RESULTS: Nine
eyes series were studied. The mean preoperative refractive cylinder correction
was 6.11 +/- 2.54 diopters (D). The mean postoperative refractive cylinder
correction was 2.85 +/- 1.31 D. The mean correction index was 1.07 +/- 0.28 D.
The mean best-corrected visual acuity improved from 20/40 to 20/22 after the 2
steps. The median follow-up was 11 (range, 9-17) months. No complications were
observed and postoperative outcome was satisfactory. CONCLUSIONS: Permitting
correction of a broader range of high astigmatism with good accuracy, this
combined approach minimizes excision of corneal stromal tissue and postoperative
complications.
PMID- 25127193
TI - Temperature-dependent phase transition and desorption free energy of sodium
dodecyl sulfate at the water/vapor interface: approaches from molecular dynamics
simulations.
AB - Adsorption of surfactants at the water/vapor interface depends upon their
chemical potential at the interface, which is generally temperature-dependent.
Molecular dynamics simulations have been performed to reveal temperature
influences on the microstructure of sodium dodecyl sulfate (SDS) molecule
adsorption layer. At room temperature, SDS molecules aggregate at the interface,
being in a liquid-expanded phase, whereas they tend to spread out and probably
transit to a gaseous phase as the temperature increases to above 318 K. This
phase transition has been confirmed by the temperature-dependent changes in two
dimensional array, tilt angles, and immersion depths to the aqueous phase of SDS
molecules. The aggregation of SDS molecules accompanies with larger immersion
depths, more coordination of Na(+) ions, and less coordination of water.
Desorption free energy profiles show that higher desorption free energy appears
for SDS molecules at the aggregate state at low temperatures, but no energy
barrier is observed. The shapes of desorption free energy profiles depend upon
the distribution of SDS at the interface, which, in turn, is related to the phase
state of SDS. Our study sheds light on the development of adsorption
thermodynamics and kinetics theories.
PMID- 25127194
TI - Anisotropic hyperelastic behavior of soft biological tissues.
AB - Constitutive laws are fundamental to the studies of the mechanically dominated
clinical interventions involving soft biological tissues which show a highly
anisotropic hyperelastic mechanical properties. The purpose of this paper was to
develop an improved constitutive law based on the Holzapfel-Gasser-Ogden's model:
to replace the isotropic part with Gent constitutive law so as to model the
noncollagenous matrix of the media due to its generality and capability to
reproduce the Neo-Hookean model. This model is implemented into an in-house
finite element program. A uniaxial tension test is considered to study the
influence of material parameter J(m) in Gent model and beta which represents the
angle between the collagen fibers and the circumferential direction. A simulation
of an adventitial strip specimen under tension is performed to show the
applicability of this constitutive law.
PMID- 25127195
TI - Reduced levels of plasma kisspeptin during the antenatal booking visit are
associated with increased risk of miscarriage.
AB - CONTEXT: Kisspeptin is a recently identified hormone encoded by the KISS1 gene,
playing a critical role in human reproduction. Plasma kisspeptin levels rise
dramatically during normal pregnancy due to placental synthesis, which implicates
it as a potential tool for assessing risks of pregnancy complications. No
previous prospective study has investigated the association between plasma
kisspeptin and risk of miscarriage. OBJECTIVE: The objective of the study was to
determine whether a single plasma kisspeptin or serum human chorionic
gonadotropin (hCG) measurement in asymptomatic women attending their booking
antenatal visit is associated with miscarriage. DESIGN: This was a prospective
cohort study. SETTING: The study was conducted at a tertiary obstetric center.
PARTICIPANTS: A total of 993 asymptomatic pregnant women with a gestation of 6
weeks or longer attending routine antenatal booking visit were recruited between
January 2010 and December 2012. MAIN OUTCOME MEASURES: Plasma kisspeptin and
serum hCG were measured during the antenatal booking visit. Pregnancy outcome was
recorded prospectively. RESULTS: Plasma kisspeptin correlated with gestation
(r(2) = 0.57; P < .0001). Gestational age-corrected (multiples of median) plasma
kisspeptin was 60.4% lower (P < .001), and multiples of median-hCG was 36.1%
lower (P < .001) in women later diagnosed with miscarriage compared with women
without miscarriage. Increased plasma kisspeptin was associated with reduced
miscarriage risk, even after adjusting for age, body mass index, gestational age,
smoking, and blood pressure [odds ratio 0.13 (95% confidence interval 0.08-0.22),
P = .0001]. Kisspeptin had a higher diagnostic performance for miscarriage than
hCG (receiver-operator characteristic-area under the curve 0.899 +/- 0.025 plasma
kisspeptin; 0.775 +/- 0.040, serum hCG, P < .01 vs plasma kisspeptin).
CONCLUSION: Our data suggest for the first time that a single plasma kisspeptin
measurement taken during the antenatal booking visit provides a potential novel
marker for identifying asymptomatic pregnant women at a gestation of 6 weeks or
greater at increased risk of miscarriage.
PMID- 25127197
TI - Drinking identity as a mediator of the relationship between drinking motives and
weekly alcohol consumption among heavy drinking undergraduate students.
AB - OBJECTIVES: The present study assessed relationships among social, coping,
enhancement, and conformity drinking motives and weekly alcohol consumption by
considering drinking identity as a mediator of this relationship. METHODS:
Participants were 260 heavy drinking undergraduate students (81% female;
Mage=23.45; SD=5.39) who completed a web-based survey. RESULTS: Consistent with
expectations, findings revealed significant direct effects of motives on drinking
identity for all four models. Further, significant direct effects emerged for
drinking identity on weekly drinking. Results partially supported predictions
that motives would have direct effects on drinks per week; total effects of
motives on drinking emerged for all models but direct effects of motives on
weekly drinking emerged for only enhancement motives. There were significant
indirect effects of motives on weekly drinking through drinking identity for all
four models. CONCLUSIONS: The findings supported the hypotheses that drinking
identity would mediate the relationship between drinking motives and alcohol
consumption. These examinations have practical utility and may inform development
and implementation of interventions and programs targeting alcohol misuse among
heavy drinking undergraduate students.
PMID- 25127198
TI - From socially prescribed perfectionism to problematic use of internet
communicative services: the mediating roles of perceived social support and the
fear of negative evaluation.
AB - BACKGROUND: The present study developed and tested a model that explains how
people who believe that others have unrealistically high standards and exert
pressure on them to be perfect (that is, people high in socially prescribed
perfectionism) develop a problematic use of internet communicative services
(GPIU). Following the perfectionism social disconnection model and previous
evidence about the role that the online environment might play in the development
of problematic internet use, low reported social support and the fear of negative
evaluations in face to face interactions were hypothesized to mediate the
association between socially prescribed perfectionism and GPIU. METHODS: A sample
of 465 undergraduate students was recruited (240 F; mean age 21.91+2.23years),
and the hypotheses were tested through structural equation modeling separately
for men and women. RESULTS: Among men, the association between SPP and GPIU was
fully mediated by the fear of being negatively evaluated and the perception of
low social support. For women, we found a partially mediated model in which SPP
affected GPIU indirectly through the fear of negative evaluations. The presence
of a direct effect of SPP on GPIU was also found. Moreover, perceived social
support was not found to be a significant mediator among women. CONCLUSIONS: The
findings suggest that problematic use of internet communicative services might
be, at least in part, a defensive response to extreme social evaluation
pressures.
PMID- 25127196
TI - The interactive effect of neighborhood peer cigarette use and 5HTTLPR genotype on
individual cigarette use.
AB - BACKGROUND: Previous cross-sectional research has shown that adolescents'
cigarette use is interactively associated with that of their school peers and
their 5HTTLPR genotype, such that the cigarette use of persons with more copies
of the 5HTTLPR*S' allele is more dependent on school peers' cigarette use
behaviors than their counterparts. This analysis seeks to extend this novel
finding by examining whether the same conclusion can be reached when substituting
neighborhood peers for school peers and examining the timing of the initiation of
any and regular smoking in adolescence. METHODS: This analysis employs an
independent sample with longitudinal measures of cigarette use among 6th through
8th graders clustered in 82 neighborhoods, of whom 1098 contributed genetic data.
The proportion of respondents who had ever smoked cigarettes by the first wave
was calculated for each census block group in the study. 5HTTLPR genotype was
assayed using the method of Whisman et al. (2011). The timing of any or regular
smoking initiation and over four years were modeled as dependent variables using
Cox proportional hazard models. RESULTS: The interaction of neighborhood peer
smoking behavior in the first wave and 5HTTLPR genotype statistically
significantly predicted any smoking initiation (hazard ratio: 3.532; p
value=0.002) and regular smoking initiation (hazard ratio: 5.686; p-value=0.000),
net of controls for sex, race/ethnicity, grade in the first wave of data, and
parental educational attainment. These findings reach the same conclusions as
previous cross-sectional research. CONCLUSIONS: These results differ in the model
of gene-environment interaction that they support. The findings for any smoking
initiation are consistent with the diathesis-stress model of gene-environment
interaction; the findings for regular smoking initiation are consistent with the
differential susceptibility model.
PMID- 25127199
TI - Revisiting the rationale for social normative interventions in student drinking
in a UK population.
AB - OBJECTIVES: Social normative re-education interventions are based on the premise
that harmful student drinking is caused by misperceptions of campus drinking
norms. They have become dominant despite little evidence for effectiveness,
especially with heavy drinkers. The objective of this study was to explore the
relative importance of social norms and other key cognitive constructs in
predicting single occasion alcohol consumption in undergraduates. METHODS:
DESIGN: A cross sectional survey design was utilised. SETTING: Three UK
universities. PARTICIPANTS: 367 1st year undergraduate students. MEASURES:
Frequency and quantity of alcohol consumed; hazardous drinking; descriptive and
injunctive normative perceptions of alcohol consumption were measured at 3
proximal-distal levels. RESULTS: Participants in this study were drinking at much
higher levels than previously reported (means of 20 units for males, 16 units for
females on a single drinking occasion); 85% exceeded the UK government's
definition of binge drinking of 8 units or more on a single occasion. Norm
perceptions, which form the basis of social normative interventions, were not
significant predictors of individual consumption. Cognitive appraisal of oneself
as a drinker and volitional behavioural control on drinking occasions are the
most important constructs in predicting heavy drinking in this sample of UK
undergraduate students. The model that emerges explains 40% of the variance in
single occasion consumption. CONCLUSIONS: Students are consuming levels of
alcohol that will result in accumulative harm if unchecked. This study provides
an explanation as to why social normative interventions are not effective. An
alternative focus for reducing alcohol consumption in UK undergraduates is
suggested.
PMID- 25127200
TI - miR-29b suppresses proliferation, migration, and invasion of tongue squamous cell
carcinoma through PTEN-AKT signaling pathway by targeting Sp1.
AB - OBJECTIVES: miR-29b has been implicated in various cancers. However, the role of
miR-29b in tongue squamous cell carcinoma (TSCC) remains unclear. This study
aimed to investigate the role of miR-29b in TSCC progression. MATERIALS AND
METHODS: The expression of miR-29b was analyzed in TSCC tissues and cells.
Functional studies were performed in TSCC cells. Real time-PCR, Western blot,
cell proliferation, transwell, and dual luciferase reporter assays were performed
according to standard procedures. RESULTS: miR-29b was significantly decreased in
TSCC specimens and cell lines compared with corresponding normal counterparts.
Overexpression of miR-29b significantly inhibited the proliferation, migration,
invasion, and cell-cycle progression of TSCC cells, and promoted apoptosis.
Moreover, miR-29b targeted the 3' untranslated region of the Sp1 transcript and
resulted in the deregulation of Sp1. The inhibition of Sp1 by miR-29b
subsequently resulted in the upregulation of PTEN, leading to a decline of
phosphorylated AKT. Knockdown of Sp1 in TSCC cell lines mimicked the effects of
miR-29b overexpression. In addition, the expression of miR-29b was inversely
correlated with Sp1 and positively correlated with the PTEN in TSCC specimens.
CONCLUSION: miR-29b functions as a tumor suppressor in TSCC, and the miR
29b/Sp1/PTEN/AKT axis might represent a potential therapeutic target for TSCC
intervention.
PMID- 25127202
TI - Direct synthesis of alpha-trifluoromethyl ketone from (hetero)arylacetylene:
design, intermediate trapping, and mechanistic investigations.
AB - Regioselective addition across the alkynes has been achieved in a silver
catalyzed protocol utilizing Langlois reagent (CF3SO2Na) and molecular O2 to
access medicinally active alpha-trifluoromethyl ketone compounds. This method was
successful in producing alpha-trifluoromethyl ketone in heterocyclic scaffolds,
which are incompatible with earlier strategies. Experimental findings suggest a
mechanism involving alpha-styrenyl radical intermediate and 1-methyl-2
pyrrolidinone (NMP) solvent, which leads to crystallographically characterized N
methylsuccinimide. Isotope labeling, kinetic studies, and intermediate trapping
further helped to gain insight into this energy-demanding process.
PMID- 25127201
TI - A systematic review of patient acceptance of screening for oral cancer outside of
dental care settings.
AB - This systematic review summarised the literature on patient acceptability of
screening for oral cancer outside dental care settings. A comprehensive search of
relevant literature was performed in EMBASE, MEDLINE, Cochrane Database of
Systematic Reviews, CINAHAL, psycINFO, CANCERLIT and BNI to identify relevant
articles published between 1975 and Dec 2013. Studies reporting acceptability of
oral cancer screening to undiagnosed individuals attending non-dental settings
were eligible for inclusion. A total of 2935 references were initially identified
from the computerised search but 2217 were excluded after screening the titles.
From the abstracts of the remaining 178 articles, 47 full text articles were
retrieved for further scrutiny, and 12 studies were found to be eligible for
inclusion. In these studies, knowledge about oral cancer, anxiety related to the
screening process, preference for care provision, and financial cost were
influencing factors for the acceptance of screening. Written information provided
to patients in primary care was reported to boost immediate knowledge levels of
oral cancer, lessen anxiety, and increase intentions for screening. The majority
of screening methods were entirely acceptable to patients; lack of acceptability
from the patients' viewpoint was not a significant barrier to carrying out
opportunistic screening of high-risk populations. In conclusion, the available
evidence suggests that acceptance of, and satisfaction with oral cancer screening
is high, particularly where patients have previously been educated about oral
cancer. Further research focusing on patient's preferences would enable
streamlining of the approach to oral cancer screening taken by any national
programme.
PMID- 25127203
TI - Analysis of CF...FC interactions on cyclohexane and naphthalene frameworks.
AB - Intramolecular CF...FC interactions in selected organofluorine compounds (all-syn
1,2,3,4- and all-syn-1,2,4,5-tetrafluorocyclohexane, 1,8-difluoronaphthalene, 4,5
difluorophenanthrene, 2,2',5,5'-tetrafluorobiphenyl) were studied at the MP2/aug
cc-pVDZ level using the recently developed noncovalent interaction (NCI) method.
For the optimized minima, all CF...FC interactions that are identified by this
method are classified as attractive, even in those cases where suitable isodesmic
reaction energies fail to provide evidence for an energetic stabilization.
Possible relations between these interactions and the observable JFF spin-spin
coupling constant values are discussed.
PMID- 25127204
TI - Pathways community HUB: a model for coordination of community health care.
PMID- 25127206
TI - Care coordination, family-centered care, and functional ability in children with
special health care needs in the United States.
AB - The purpose of this study was to determine if there was an association between
care coordination, family-centered care, and functional ability among children
with special health care needs (CSHCN). Analysis of data from the 2005-2006
National Survey of CSHCN revealed that the percentages of CSHCN receiving care
coordination and family-centered care were 59.3 and 66.3, respectively. Children
who did not receive care coordination had a 53% higher adjusted odds (odds
ratio=1.53, 95% confidence interval 1.21-1.94, P<0.001) for a limitation in
functional ability compared to CSHCN who received care coordination. Family
centered care was not associated with a limitation in functional ability in CSHCN
(P=0.61). CSHCN are underserved with regard to care coordination and this appears
to be associated with impaired functional ability. Longitudinal studies are
needed to confirm causality.
PMID- 25127205
TI - Failure to reach target glycated a1c levels among patients with diabetes who are
adherent to their antidiabetic medication.
AB - The objectives of this study were to describe patient characteristics and types
of medications taken by those with poor glycemic control (A1c>7%) despite being
adherent to antidiabetic medications. This is a retrospective analysis of
administrative data from adult patients with diabetes enrolled in a large health
plan in Hawaii (n=21,267 observations for 11,013 individuals) and adherent to
their antidiabetic medications. Multivariable logistic regressions were estimated
to determine characteristics and types of medications associated with poor
glycemic control. Separate models were estimated to examine category of
medication (insulin only, 1 oral medication, multiple oral medications, both oral
medications and insulin) and specific therapeutic class of oral antidiabetic
medications. Despite being adherent to their medications, 56.1% of patients had
poor glycemic control. Compared to patients taking combination sulfonylureas,
patients had a higher odds of having A1c>7% for all other oral diabetic
medications, with odds ratios ranging from OR=2.07 for sulfonylureas alone to
OR=1.33 for combination DPP-4 inhibitors. More than half of patients in this
study had poor A1c control despite being adherent to their medications. This
suggests that physicians, pharmacists, and other providers may need to monitor
treatment regimens more carefully, encourage healthy behaviors, and intensify
pharmacological treatment as needed.
PMID- 25127207
TI - Ponesimod--a future oral therapy for psoriasis?
PMID- 25127208
TI - Oral ponesimod in patients with chronic plaque psoriasis: a randomised, double
blind, placebo-controlled phase 2 trial.
AB - BACKGROUND: We assessed the efficacy, safety, and tolerability of ponesimod, an
oral, selective, reversible modulator of sphingosine 1-phosphate receptor 1, in
patients with moderate to severe chronic plaque psoriasis. METHODS: Between Sept
22, 2010, and Oct 24, 2012, patients with psoriasis area and severity index
(PASI) scores higher than 10 were enrolled into this multicentre double-blind,
phase 2 study. They received 20 mg or 40 mg ponesimod or placebo once daily for
16 weeks. Those with at least 50% reduction in PASI score at 16 weeks and who
were receiving ponesimod were rerandomised to receive maintenance ponesimod
therapy or placebo until week 28. The primary endpoint was reduction in PASI
score from baseline of at least 75% (PASI75) at week 16. This study is registered
with ClinicalTrials.gov, number NCT01208090. FINDINGS: Of 326 patients initially
randomised (20 mg ponesimod n=126, 40 mg ponesimod n=133, and placebo n=67)
PASI75 was achieved at week 16 in 58 (46.0%), 64 (48.1%), and nine (13.4%),
respectively. The treatment effect was significant for the two ponesimod doses
(both p<0.0001). Of 219 patients who entered the maintenance period, PASI75 was
achieved by week 28 in 35 (71.4%) of 49 who continued on 20 mg ponesimod and 41
(77.4%) of 53 on 40 mg ponesimod, and in 19 (42.2%) of 45 who swapped from 20 mg
to placebo and 19 (40.4%) of 47 from 40 mg to placebo. Ponesimod was associated
with dyspnoea, raised liver enzyme concentrations, and dizziness. INTERPRETATION:
Significant clinical benefit was seen at week 16 that increased with maintenance
therapy. FUNDING: Actelion Pharmaceuticals.
PMID- 25127209
TI - Pretransfusion testing and transfusion of uncrossmatched erythrocytes.
PMID- 25127210
TI - Lack of nephrotoxicity by 6% hydroxyethyl starch 130/0.4 during hip arthroplasty:
a randomized controlled trial.
AB - BACKGROUND: Hydroxyethyl starch (HES) is commonly used as plasma expander during
surgery but may be nephrotoxic as seen in studies in patients with sepsis. The
authors hypothesized that the possible nephrotoxicity of 6% HES 130/0.4 could be
revealed by measurements of urinary excretion of neutrophil gelatinase-associated
lipocalin (u-NGAL) in patients with normal renal function during hip
arthroplasty. METHODS: In this randomized, double-blinded, placebo-controlled
study, 40 patients referred for hip arthroplasty received either 6% HES 130/0.4
or isotonic saline 0.9%; 7.5 ml/kg during the first hour of surgery and 5 ml/kg
during the following hours; 38 patients completed the study. U-NGAL, urine
albumin, blood pressure, and plasma concentrations of creatinine, renin, NGAL,
albumin, angiotensin-II, and aldosterone were measured before, during, and after
surgery. U-NGAL was defined as primary outcome. RESULTS: There were no
significant differences in U-NGAL (mean difference and 95% CI), plasma
creatinine, and urine albumin during the study. U-NGAL and urine albumin
increased significantly in both groups the morning after surgery but was
normalized at follow-up after 10 to 12 days. Mean arterial pressure was
significantly higher during the recovery period in the HES group compared with
that in the control group (91 [13] and 83 [6] mmHg, mean [SD], P < 0.03). Plasma
renin and angiotensin-II were nonsignificantly different in both groups, whereas
plasma aldosterone was significantly lower in the HES group. Plasma albumin was
reduced in both groups, but to a significantly lower level in the HES group.
CONCLUSION: The study showed no evidence of a harmful effect of intraoperative
infusion of 6% HES 130/0.4 on renal function in patients during hip arthroplasty.
PMID- 25127212
TI - Repeated evolutionary changes of leaf morphology caused by mutations to a
homeobox gene.
AB - Elucidating the genetic basis of morphological changes in evolution remains a
major challenge in biology. Repeated independent trait changes are of particular
interest because they can indicate adaptation in different lineages or genetic
and developmental constraints on generating morphological variation. In animals,
changes to "hot spot" genes with minimal pleiotropy and large phenotypic effects
underlie many cases of repeated morphological transitions. By contrast, only few
such genes have been identified from plants, limiting cross-kingdom comparisons
of the principles of morphological evolution. Here, we demonstrate that the
REDUCED COMPLEXITY (RCO) locus underlies more than one naturally evolved change
in leaf shape in the Brassicaceae. We show that the difference in leaf margin
dissection between the sister species Capsella rubella and Capsella grandiflora
is caused by cis-regulatory variation in the homeobox gene RCO-A, which alters
its activity in the developing lobes of the leaf. Population genetic analyses in
the ancestral C. grandiflora indicate that the more-active C. rubella haplotype
is derived from a now rare or lost C. grandiflora haplotype via additional
mutations. In Arabidopsis thaliana, the deletion of the RCO-A and RCO-B genes has
contributed to its evolutionarily derived smooth leaf margin, suggesting the RCO
locus as a candidate for an evolutionary hot spot. We also find that temperature
responsive expression of RCO-A can explain the phenotypic plasticity of leaf
shape to ambient temperature in Capsella, suggesting a molecular basis for the
well-known negative correlation between temperature and leaf margin dissection.
PMID- 25127211
TI - Modification of the association between PM10 and lung function decline by
cadherin 13 polymorphisms in the SAPALDIA cohort: a genome-wide interaction
analysis.
AB - BACKGROUND: Both air pollution and genetic variation have been shown to affect
lung function. Their interaction has not been studied on a genome-wide scale to
date. OBJECTIVES: We aimed to identify, in an agnostic fashion, genes that modify
the association between long-term air pollution exposure and annual lung function
decline in an adult population-based sample. METHODS: A two-stage genome-wide
interaction study was performed. The discovery (n = 763) and replication (n =
3,896) samples were derived from the multi-center SAPALDIA cohort (Swiss Cohort
Study on Air Pollution and Lung Disease in Adults). Annual rate of decline in the
forced mid-expiratory flow (FEF25-75%) was the main end point. Multivariate
linear regression analyses were used to identify potential multiplicative
interactions between genotypes and 11-year cumulative PM10 exposure. RESULTS: We
identified a cluster of variants intronic to the CDH13 gene as the only locus
with genome-wide significant interactions. The strongest interaction was observed
for rs2325934 (p = 8.8 * 10(-10)). Replication of the interaction between this
CDH13 variant and cumulative PM10 exposure on annual decline in FEF25-75% was
successful (p = 0.008). The interaction was not sensitive to adjustment for
smoking or body weight. CONCLUSIONS: CDH13 is functionally linked to the
adipokine adiponectin, an inflammatory regulator. Future studies need to confirm
the interaction and assess how the result relates to previously observed
interactions between air pollution and obesity on respiratory function.
PMID- 25127214
TI - The receptor-like kinase FERONIA is required for mechanical signal transduction
in Arabidopsis seedlings.
AB - Among the myriad cues that constantly inform plant growth and development,
mechanical forces are unique in that they are an intrinsic result of cellular
turgor pressure and also imposed by the environment. Although the key role of
mechanical forces in shaping plant architecture from the cellular level to the
level of organ formation is well established, the components of the early
mechanical signal transduction machinery remain to be defined at the molecular
level. Here, we show that an Arabidopsis mutant lacking the receptor-like kinase
FERONIA (FER) shows severely altered Ca(2+) signaling and growth responses to
different forms of mechanical perturbation. Ca(2+) signals are either abolished
or exhibit qualitatively different signatures in feronia (fer) mutants exposed to
local touch or bending stimulation. Furthermore, mechanically induced
upregulation of known touch-responsive genes is significantly decreased in fer
mutants. In addition to these defects in mechanical signaling, fer mutants also
exhibit growth phenotypes consistent with impaired mechanical development,
including biased root skewing, an inability to penetrate hard agar layers, and
abnormal growth responses to impenetrable obstacles. Finally, high-resolution
kinematic analysis of root growth revealed that fer mutants show pronounced
spatiotemporal fluctuations in root cell expansion profiles with a timescale of
minutes. Based on these results, we propose that FER is a key regulator of
mechanical Ca(2+) signaling and that FER-dependent mechanical signaling functions
to regulate growth in response to external or intrinsic mechanical forces.
PMID- 25127213
TI - Dynamic localization of the cyanobacterial circadian clock proteins.
AB - BACKGROUND: The cyanobacterial circadian clock system has been extensively
studied, and the structures, interactions, and biochemical activities of the
central oscillator proteins (KaiA, KaiB, and KaiC) have been well elucidated.
Despite this rich repository of information, little is known about the
distribution of these proteins within the cell. RESULTS: Here we report that KaiA
and KaiC localize as discrete foci near a single pole of cells in a clock
dependent fashion, with enhanced polar localization observed at night. KaiA
localization is dependent on KaiC; consistent with this notion, KaiA and KaiC
colocalize with each other, as well as with CikA, a key input and output factor
previously reported to display unipolar localization. The molecular mechanism
that localizes KaiC to the poles is conserved in Escherichia coli, another Gram
negative rod-shaped bacterium, suggesting that KaiC localization is not dependent
on other clock- or cyanobacterial-specific factors. Moreover, expression of CikA
mutant variants that distribute diffusely results in the striking delocalization
of KaiC. CONCLUSIONS: This work shows that the cyanobacterial circadian system
undergoes a circadian orchestration of subcellular organization. We propose that
the observed spatiotemporal localization pattern represents a novel layer of
regulation that contributes to the robustness of the clock by facilitating
protein complex formation and synchronizing the clock with environmental stimuli.
PMID- 25127215
TI - Class I TCP-DELLA interactions in inflorescence shoot apex determine plant
height.
AB - Regulation of plant height, one of the most important agronomic traits, is the
focus of intensive research for improving crop performance. Stem elongation takes
place as a result of repeated cell divisions and subsequent elongation of cells
produced by apical and intercalary meristems. The gibberellin (GA) phytohormones
have long been known to control stem and internodal elongation by stimulating the
degradation of nuclear growth-repressing DELLA proteins; however, the mechanism
allowing GA-responsive growth is only slowly emerging. Here, we show that DELLAs
directly regulate the activity of the plant-specific class I TCP transcription
factor family, key regulators of cell proliferation. Our results demonstrate that
class I TCP factors directly bind the promoters of core cell-cycle genes in
Arabidopsis inflorescence shoot apices while DELLAs block TCP function by binding
to their DNA-recognition domain. GAs antagonize such repression by promoting
DELLA destruction and therefore cause a concomitant accumulation of TCP factors
on promoters of cell-cycle genes. Consistent with this model, the quadruple
mutant tcp8 tcp14 tcp15 tcp22 exhibits severe dwarfism and reduced responsiveness
to GA action. Altogether, we conclude that GA-regulated DELLA-TCP interactions in
inflorescence shoot apex provide a novel mechanism to control plant height.
PMID- 25127216
TI - Matrix elasticity regulates lamin-A,C phosphorylation and turnover with feedback
to actomyosin.
AB - Tissue microenvironments are characterized not only in terms of chemical
composition but also by collective properties such as stiffness, which influences
the contractility of a cell, its adherent morphology, and even differentiation.
The nucleoskeletal protein lamin-A,C increases with matrix stiffness, confers
nuclear mechanical properties, and influences differentiation of mesenchymal stem
cells (MSCs), whereas B-type lamins remain relatively constant. Here we show in
single-cell analyses that matrix stiffness couples to myosin-II activity to
promote lamin-A,C dephosphorylation at Ser22, which regulates turnover, lamina
physical properties, and actomyosin expression. Lamin-A,C phosphorylation is low
in interphase versus dividing cells, and its levels rise with states of nuclear
rounding in which myosin-II generates little to no tension. Phosphorylated lamin
A,C localizes to nucleoplasm, and phosphorylation is enriched on lamin-A,C
fragments and is suppressed by a cyclin-dependent kinase (CDK) inhibitor. Lamin
A,C knockdown in primary MSCs suppresses transcripts predominantly among
actomyosin genes, especially in the serum response factor (SRF) pathway. Levels
of myosin-IIA thus parallel levels of lamin-A,C, with phosphosite mutants
revealing a key role for phosphoregulation. In modeling the system as a
parsimonious gene circuit, we show that tension-dependent stabilization of lamin
A,C and myosin-IIA can suitably couple nuclear and cell morphology downstream of
matrix mechanics.
PMID- 25127218
TI - Anisotropic diffusion of macromolecules in the contiguous nucleocytoplasmic fluid
during eukaryotic cell division.
AB - Character and rapidity of protein diffusion in intracellular fluids are key
determinants of the dynamics and steady state of a plethora of biochemical
reactions. So far, an anomalous diffusion in cytoplasmic fluids with viscoelastic
and even glassy characteristics has been reported in a variety of organisms on
several length scales and timescales. Here, we show that the contiguous fluid of
former cytoplasm and nucleoplasm features an anisotropically varying diffusion of
macromolecules during eukaryotic cell division. In metaphase, diffusion in the
contiguous nucleocytoplasmic fluid appears less anomalous along the spindle axis
as compared to perpendicular directions. As a consequence, the long-time
diffusion of macromolecules preferentially points along the spindle axis, leading
to prolonged residence of macromolecules in the spindle region. Based on our
experimental data, we suggest that anisotropic diffusion facilitates the
encounter and interaction of spindle-associated proteins, e.g., during the
formation of a dynamic spindle matrix.
PMID- 25127217
TI - Regulation of YAP by mechanical strain through Jnk and Hippo signaling.
AB - Mechanical forces affect all the tissues of our bodies. Experiments conducted
mainly on cultured cells have established that altering these forces influences
cell behaviors, including migration, differentiation, apoptosis, and
proliferation [1, 2]. The transcriptional coactivator YAP has been identified as
a nuclear relay of mechanical signals, but the molecular mechanisms that lead to
YAP activation were not identified [3]. YAP is the main transcriptional effector
of the Hippo signaling pathway, a major growth regulatory pathway within metazoa
[4], but at least in some instances, the influence of mechanical strain on YAP
was reported to be independent of Hippo signaling [5, 6]. Here, we identify a
molecular pathway that can promote the proliferation of cultured mammary
epithelial cells in response to cyclic or static stretch. These mechanical
stimuli are associated with increased activity of the transcriptional coactivator
YAP, which is due at least in part to inhibition of Hippo pathway activity. Much
of this influence on Hippo signaling can be accounted for by the activation of c
Jun N-terminal kinase (JNK) activity by mechanical strain and subsequent
inhibition of Hippo signaling by JNK. LATS1 is a key negative regulator of YAP
within the Hippo pathway, and we further show that cyclic stretch is associated
with a JNK-dependent increase in binding of a LATS inhibitor, LIMD1, to the LATS1
kinase and that reduction of LIMD1 expression suppresses the activation of YAP by
cyclic stretch. Together, these observations establish a pathway for mechanical
regulation of cell proliferation via JNK-mediated inhibition of Hippo signaling.
PMID- 25127219
TI - Clonal relationships impact neuronal tuning within a phylogenetically ancient
vertebrate brain structure.
AB - Understanding how neurons acquire specific response properties is a major goal in
neuroscience. Recent studies in mouse neocortex have shown that "sister neurons"
derived from the same cortical progenitor cell have a greater probability of
forming synaptic connections with one another and are biased to respond to
similar sensory stimuli. However, it is unknown whether such lineage-based rules
contribute to functional circuit organization across different species and brain
regions. To address this question, we examined the influence of lineage on the
response properties of neurons within the optic tectum, a visual brain area found
in all vertebrates. Tectal neurons possess well-defined spatial receptive fields
(RFs) whose center positions are retinotopically organized. If lineage
relationships do not influence the functional properties of tectal neurons, one
prediction is that the RF positions of sister neurons should be no more (or less)
similar to one another than those of neighboring control neurons. To test this
prediction, we developed a protocol to unambiguously identify the daughter
neurons derived from single tectal progenitor cells in Xenopus laevis tadpoles.
We combined this approach with in vivo two-photon calcium imaging in order to
characterize the RF properties of tectal neurons. Our data reveal that the RF
centers of sister neurons are significantly more similar than would be expected
by chance. Ontogenetic relationships therefore influence the fine-scale
topography of the retinotectal map, indicating that lineage relationships may
represent a general and evolutionarily conserved principle that contributes to
the organization of neural circuits.
PMID- 25127222
TI - Proposed US Food and Drug Administration guidance for industry on distributing
medical publications about the risks of prescription drugs and biological
products: a misguided approach.
PMID- 25127220
TI - WOX5 suppresses CYCLIN D activity to establish quiescence at the center of the
root stem cell niche.
AB - In Arabidopsis, stem cells maintain the provision of new cells for root growth.
They surround a group of slowly dividing cells named the quiescent center (QC),
and, together, they form the stem cell niche (SCN). The QC acts as the signaling
center of the SCN, repressing differentiation of the surrounding stem cells and
providing a pool of cells able to replace damaged stem cells. Maintenance of the
stem cells depends on the transcription factor WUSCHEL-RELATED HOMEOBOX 5 (WOX5),
which is specifically expressed in the QC. However, the molecular mechanisms by
which WOX5 promotes stem cell fate and whether WOX5 regulates proliferation of
the QC are unknown. Here, we reveal a new role for WOX5 in restraining cell
division in the cells of the QC, thereby establishing quiescence. In contrast,
WOX5 and CYCD3;3/CYCD1;1 both promote cell proliferation in the nascent
columella. The additional QC divisions occurring in wox5 mutants are suppressed
in mutant combinations with the D type cyclins CYCD3;3 and CYCD1;1. Moreover,
ectopic expression of CYCD3;3 in the QC is sufficient to induce cell division in
the QC. WOX5 thus suppresses QC divisions that are otherwise promoted by CYCD3;3
and CYCD1;1, in part by interacting with the CYCD3;3 promoter to repress CYCD3;3
expression in the QC. Therefore, we propose a specific role for WOX5 in
initiating and maintaining quiescence of the QC by excluding CYCD activity from
the QC.
PMID- 25127223
TI - Potential torsades de pointes triggered by hypokalemia related to olanzapine in a
patient with implantable cardioverter-defibrillator.
PMID- 25127224
TI - Continuing quality enhancement.
PMID- 25127221
TI - Rhythms in energy storage control the ability of the cyanobacterial circadian
clock to reset.
AB - Circadian clocks are oscillatory systems that schedule daily rhythms of
organismal behavior. The ability of the clock to reset its phase in response to
external signals is critical for proper synchronization with the environment. In
the model clock from cyanobacteria, the KaiABC proteins that comprise the core
oscillator are directly sensitive to metabolites. Reduced ATP/ADP ratio and
oxidized quinones cause clock phase shifts in vitro. However, it is unclear what
determines the metabolic response of the cell to darkness and thus the magnitude
of clock resetting. We show that the cyanobacterial circadian clock generates a
rhythm in metabolism that causes cells to accumulate glycogen in anticipation of
nightfall. Mutation of the histidine kinase CikA creates an insensitive clock
input phenotype by misregulating clock output genome wide, leading to
overaccumulation of glycogen and subsequently high ATP in the dark. Conversely,
we show that disruption of glycogen metabolism results in low ATP in the dark and
makes the clock hypersensitive to dark pulses. The observed changes in cellular
energy are sufficient to recapitulate phase-shifting phenotypes in an in vitro
model of the clock. Our results show that clock-input phenotypes can arise from
metabolic dysregulation and illustrate a framework for circadian biology where
clock outputs feed back through metabolism to control input mechanisms.
PMID- 25127225
TI - Ultrasound of the fetal veins part 2: Veins at the cardiac level.
AB - In recent years the advent of high-resolution and color Doppler ultrasound has
enabled a more comprehensive examination of the veins at the cardiac level. These
veins include both the superior and inferior vena cava, the pulmonary veins, the
azygos vein, the coronary sinus, and the brachiocephalic (or innominate) vein.
This article gives a review of the normal and abnormal conditions of the cardiac
venous system. Normal anatomy and abnormal findings of these veins are
demonstrated by grayscale and color Doppler. Three groups of anomalies are
presented: 1) the interrupted inferior vena cava with azygos continuity, 2) the
left persisting superior vena cava and 3) the total and partial anomalous
pulmonary venous connections. Many of these abnormal findings can be detected by
a dedicated examination of the veins during fetal echocardiography, but some
anomalies are detectable by focusing on indirect signs such as the compensatory
dilation of other veins.
PMID- 25127226
TI - Letter to the editor: Mostbeck G. Elastography everywhere--now even the lungs!
Ultraschall in Med. 2014; 35: 5 - 8.
PMID- 25127227
TI - Associations between depression and diabetes in the community: do symptom
dimensions matter? Results from the Gutenberg Health Study.
AB - OBJECTIVES: While a bidirectional relationship between diabetes and depression
has been established, there is little knowledge if the associations are due to
somatic-affective or cognitive-affective dimensions of depression. RESEARCH
DESIGN AND METHODS: In a population-based, representative survey of 15.010
participants we therefore studied the associations of the two dimensions of
depression with diabetes and health care utilization among depressed and diabetic
participants. Depression was assessed by the Patient Health Questionnaire PHQ-9.
RESULTS: We found a linear and consistent association between the intensity of
depression and the presence of diabetes increasing from 6.9% in no or minimal
depression to 7.6% in mild, 9% in moderate and 10.5% in severe depression. There
was a strong positive association between somatic-affective symptoms but not with
cognitive-affective symptoms and diabetes. Depression and diabetes were both
independently related to somatic health care utilisation. CONCLUSIONS: Diabetes
and depression are associated, and the association is primarily driven by the
somatic-affective component of depression. The main limitation of our study
pertains to the cross-sectional data acquisition. Further longitudinal work on
the relationship of obesity and diabetes should differentiate the somatic and the
cognitive symptoms of depression.
PMID- 25127228
TI - Influence of tetracycline on the microbial community composition and activity of
nitrifying biofilms.
AB - The present work aims to evaluate the bacterial composition and activity (carbon
and nitrogen removal) of nitrifying biofilms exposed to 50 MUg L(-1) of
tetracycline. The tetracycline removal efficiency and the occurrence of
tetracycline resistance (tet) genes were also studied. Two sequencing batch
biofilm reactors (SBBRs) fed with synthetic wastewater were operated without
(SBBR1) and with (SBBR2) the antibiotic. Both SBBRs showed similar organic matter
biodegradation and nitrification activity. Tetracycline removal was about 28% and
biodegradation was probably the principal removal mechanism of the antibiotic.
Polymerase chain reaction-denaturing gradient gel electrophoresis analysis of the
bacterial community showed shifts leading to not only the fading of some
ribotypes, but also the emergence of new ones in the biofilm with tetracycline.
The study of the tet genes showed that tet(S) was only detected in the biofilm
with tetracycline, suggesting a relationship between its occurrence and the
presence of the antibiotic.
PMID- 25127229
TI - Chemical and mechanical defenses vary among maternal lines and leaf ages in
Verbascum thapsus L. (Scrophulariaceae) and reduce palatability to a generalist
insect.
AB - Intra-specific variation in host-plant quality affects herbivore foraging
decisions and, in turn, herbivore foraging decisions mediate plant fitness. In
particular, variation in defenses against herbivores, both among and within
plants, shapes herbivore behavior. If variation in defenses is genetically based,
it can respond to natural selection by herbivores. We quantified intra-specific
variation in iridoid glycosides, trichome length, and leaf strength in common
mullein (Verbascum thapsus L, Scrophulariaceae) among maternal lines within a
population and among leaves within plants, and related this variation to feeding
preferences of a generalist herbivore, Trichopulsia ni Hubner. We found
significant variation in all three defenses among maternal lines, with T. ni
preferring plants with lower investment in chemical, but not mechanical, defense.
Within plants, old leaves had lower levels of all defenses than young leaves, and
were strongly preferred by T. ni. Caterpillars also preferred leaves with
trichomes removed to leaves with trichomes intact. Differences among maternal
lines indicate that phenotypic variation in defenses likely has a genetic basis.
Furthermore, these results reveal that the feeding behaviors of T. ni map onto
variation in plant defense in a predictable way. This work highlights the
importance of variation in host-plant quality in driving interactions between
plants and their herbivores.
PMID- 25127230
TI - Behavior of the potential antitumor V(IV)O complexes formed by flavonoid ligands.
1. Coordination modes and geometry in solution and at the physiological pH.
AB - The coordination modes and geometry assumed in solution by the potent antitumor
oxidovanadium(IV) complexes formed by different flavonoids were studied by
spectroscopic (Electron Paramagnetic Resonance, EPR) and computational (Density
Functional Theory, DFT) methods. A series of bidentate flavonoid ligands (L) with
increasing structural complexity was examined, which can involve (CO, O(-))
donors and formation of five- and six-membered chelate rings, or (O(-), O(-))
donors and five-membered chelate rings. The geometry corresponding to these
coordination modes can be penta-coordinated, [VOL2], or cis-octahedral, cis
[VOL2(H2O)]. The results show that, at physiological pH, ligands provided with
(CO, O(-)) donor set yield cis-octahedral species with "maltol-like" coordination
when five-membered chelate rings are formed (as with 3-hydroxyflavone), while
penta-coordinated structures with "acetylacetone-like" coordination are preferred
when the chelate rings are six-membered (as with chrysin). When both the binding
modes are possible, as with morin, the "acetylacetone-like" coordination is
observed. For the ligands containing a catecholic donor set, such as 7,8
dihydroxyflavone, baicalein, fisetin, quercetin and rutin, the formation of
square pyramidal complexes with (O(-), O(-)) "catechol-like" coordination and
five-membered chelate rings is preferred at physiological pH. The determination
of the different coordination modes and geometry is important to define the
biotransformation in the blood and the interaction of these complexes with the
biological membranes.
PMID- 25127231
TI - Pallidal neurostimulation in patients with medication-refractory cervical
dystonia: a randomised, sham-controlled trial.
AB - BACKGROUND: Cervical dystonia is managed mainly by repeated botulinum toxin
injections. We aimed to establish whether pallidal neurostimulation could improve
symptoms in patients not adequately responding to chemodenervation or oral drug
treatment. METHODS: In this randomised, sham-controlled trial, we recruited
patients with cervical dystonia from centres in Germany, Norway, and Austria.
Eligible patients (ie, those aged 18-75 years, disease duration >=3 years,
Toronto Western Spasmodic Torticollis Rating Scale [TWSTRS] severity score >=15
points) were randomly assigned (1:1) to receive active neurostimulation
(frequency 180 Hz; pulse width 120 MUs; amplitude 0.5 V below adverse event
threshold) or sham stimulation (amplitude 0 V) by computer-generated
randomisation lists with randomly permuted block lengths stratified by centre.
All patients, masked to treatment assignment, were implanted with a deep brain
stimulation device and received their assigned treatment for 3 months.
Neurostimulation was activated in the sham group at 3 months and outcomes were
reassessed in all patients after 6 months of active treatment. Treating
physicians were not masked. The primary endpoint was the change in the TWSTRS
severity score from baseline to 3 months, assessed by two masked dystonia experts
using standardised videos, analysed by intention to treat. This trial is
registered with ClinicalTrials.gov, number NCT00148889. FINDINGS: Between Jan 19,
2006, and May 29, 2008, we recruited 62 patients, of whom 32 were randomly
assigned to neurostimulation and 30 to sham stimulation. Outcome data were
recorded in 60 (97%) patients at 3 months and 56 (90%) patients at 6 months. At 3
months, the reduction in dystonia severity was significantly greater with
neurostimulation (-5.1 points [SD 5.1], 95% CI -7.0 to -3.5) than with sham
stimulation (-1.3 [2.4], -2.2 to -0.4, p=0.0024; mean between-group difference
3.8 points, 1.8 to 5.8) in the intention-to-treat population. Over the course of
the study, 21 adverse events (five serious) were reported in 11 (34%) of 32
patients in the neurostimulation group compared with 20 (11 serious) in nine
(30%) of 30 patients in the sham-stimulation group. Serious adverse events were
typically related to the implant procedure or the implanted device, and 11 of 16
resolved without sequelae. Dysarthria (in four patients assigned to
neurostimulation vs three patients assigned to sham stimulation), involuntary
movements (ie, dyskinesia or worsening of dystonia; five vs one), and depression
(one vs two) were the most common non-serious adverse events reported during the
course of the study. INTERPRETATION: Pallidal neurostimulation for 3 months is
more effective than sham stimulation at reducing symptoms of cervical dystonia.
Extended follow-up is needed to ascertain the magnitude and stability of chronic
neurostimulation effects before this treatment can be recommended as routine for
patients who are not responding to conventional medical therapy. FUNDING:
Medtronic.
PMID- 25127233
TI - Lost in space: sleep.
PMID- 25127232
TI - Prevalence of sleep deficiency and use of hypnotic drugs in astronauts before,
during, and after spaceflight: an observational study.
AB - BACKGROUND: Sleep deprivation and fatigue are common subjective complaints among
astronauts. Previous studies of sleep and hypnotic drug use in space have been
limited to post-flight subjective survey data or in-flight objective data
collection from a small number of crew members. We aimed to characterise
representative sleep patterns of astronauts on both short-duration and long
duration spaceflight missions. METHODS: For this observational study, we
recruited crew members assigned to Space Transportation System shuttle flights
with in-flight experiments between July 12, 2001, and July 21, 2011, or assigned
to International Space Station (ISS) expeditions between Sept 18, 2006, and March
16, 2011. We assessed sleep-wake timing objectively via wrist actigraphy, and
subjective sleep characteristics and hypnotic drug use via daily logs, in-flight
and during Earth-based data-collection intervals: for 2 weeks scheduled about 3
months before launch, 11 days before launch until launch day, and for 7 days upon
return to Earth. FINDINGS: We collected data from 64 astronauts on 80 space
shuttle missions (26 flights, 1063 in-flight days) and 21 astronauts on 13 ISS
missions (3248 in-flight days), with ground-based data from all astronauts (4014
days). Crew members attempted and obtained significantly less sleep per night as
estimated by actigraphy during space shuttle missions (7.35 h [SD 0.47]
attempted, 5.96 h [0.56] obtained), in the 11 days before spaceflight (7.35 h
[0.51], 6.04 h [0.72]), and about 3 months before spaceflight (7.40 h [0.59],
6.29 h [0.67]) compared with the first week post-mission (8.01 h [0.78], 6.74 h
[0.91]; p<0.0001 for both measures). Crew members on ISS missions obtained
significantly less sleep during spaceflight (6.09 h [0.67]), in the 11 days
before spaceflight (5.86 h [0.94]), and during the 2-week interval scheduled
about 3 months before spaceflight (6.41 h [SD 0.65]) compared with in the first
week post-mission (6.95 h [1.04]; p<0.0001). 61 (78%) of 78 shuttle-mission crew
members reported taking a dose of sleep-promoting drug on 500 (52%) of 963
nights; 12 (75%) of 16 ISS crew members reported using sleep-promoting drugs.
INTERPRETATION: Sleep deficiency in astronauts was prevalent not only during
space shuttle and ISS missions, but also throughout a 3 month preflight training
interval. Despite chronic sleep curtailment, use of sleep-promoting drugs was
pervasive during spaceflight. Because chronic sleep loss leads to performance
decrements, our findings emphasise the need for development of effective
countermeasures to promote sleep. FUNDING: The National Aeronautics and Space
Administration.
PMID- 25127234
TI - Deep brain stimulation for cervical dystonia.
PMID- 25127237
TI - Reporting tumor molecular heterogeneity in histopathological diagnosis.
AB - BACKGROUND: Detection of molecular tumor heterogeneity has become of paramount
importance with the advent of targeted therapies. Analysis for detection should
be comprehensive, timely and based on routinely available tumor samples. AIM: To
evaluate the diagnostic potential of targeted multigene next-generation
sequencing (TM-NGS) in characterizing gastrointestinal cancer molecular
heterogeneity. METHODS: 35 gastrointestinal tract tumors, five of each intestinal
type gastric carcinomas, pancreatic ductal adenocarcinomas, pancreatic
intraductal papillary mucinous neoplasms, ampulla of Vater carcinomas,
hepatocellular carcinomas, cholangiocarcinomas, pancreatic solid pseudopapillary
tumors were assessed for mutations in 46 cancer-associated genes, using Ion
Torrent semiconductor-based TM-NGS. One ampulla of Vater carcinoma cell line and
one hepatic carcinosarcoma served to assess assay sensitivity. TP53, PIK3CA,
KRAS, and BRAF mutations were validated by conventional Sanger sequencing.
RESULTS: TM-NGS yielded overlapping results on matched fresh-frozen and formalin
fixed paraffin-embedded (FFPE) tissues, with a mutation detection limit of 1% for
fresh-frozen high molecular weight DNA and 2% for FFPE partially degraded DNA. At
least one somatic mutation was observed in all tumors tested; multiple
alterations were detected in 20/35 (57%) tumors. Seven cancers displayed
significant differences in allelic frequencies for distinct mutations, indicating
the presence of intratumor molecular heterogeneity; this was confirmed on
selected samples by immunohistochemistry of p53 and Smad4, showing concordance
with mutational analysis. CONCLUSIONS: TM-NGS is able to detect and quantitate
multiple gene alterations from limited amounts of DNA, moving one step closer to
a next-generation histopathologic diagnosis that integrates morphologic,
immunophenotypic, and multigene mutational analysis on routinely processed
tissues, essential for personalized cancer therapy.
PMID- 25127238
TI - Interplay between parasitism and host ontogenic resistance in the epidemiology of
the soil-borne plant pathogen Rhizoctonia solani.
AB - Spread of soil-borne fungal plant pathogens is mainly driven by the amount of
resources the pathogen is able to capture and exploit should it behave either as
a saprotroph or a parasite. Despite their importance in understanding the fungal
spread in agricultural ecosystems, experimental data related to exploitation of
infected host plants by the pathogen remain scarce. Using Rhizoctonia solani /
Raphanus sativus as a model pathosystem, we have obtained evidence on the link
between ontogenic resistance of a tuberizing host and (i) its susceptibility to
the pathogen and (ii) after infection, the ability of the fungus to spread in
soil. Based on a highly replicable experimental system, we first show that
infection success strongly depends on the host phenological stage. The nature of
the disease symptoms abruptly changes depending on whether infection occurred
before or after host tuberization, switching from damping-off to necrosis
respectively. Our investigations also demonstrate that fungal spread in soil
still depends on the host phenological stage at the moment of infection. High,
medium, or low spread occurred when infection was respectively before, during, or
after the tuberization process. Implications for crop protection are discussed.
PMID- 25127239
TI - Crystal structure of a complex of NOD1 CARD and ubiquitin.
AB - The Caspase Recruitment Domain (CARD) from the innate immune receptor NOD1 was
crystallized with Ubiquitin (Ub). NOD1 CARD was present as a helix-swapped
homodimer similar to other structures of NOD1 CARD, and Ub monomers formed a
homodimer similar in conformation to Lys48-linked di-Ub. The interaction between
NOD1 CARD and Ub in the crystal was mediated by novel binding sites on each
molecule. Comparisons of these sites to previously identified interaction
surfaces on both molecules were made along with discussion of their potential
functional significance.
PMID- 25127240
TI - A systems biology approach investigating the effect of probiotics on the vaginal
microbiome and host responses in a double blind, placebo-controlled clinical
trial of post-menopausal women.
AB - A lactobacilli dominated microbiota in most pre and post-menopausal women is an
indicator of vaginal health. The objective of this double blinded, placebo
controlled crossover study was to evaluate in 14 post-menopausal women with an
intermediate Nugent score, the effect of 3 days of vaginal administration of
probiotic L. rhamnosus GR-1 and L. reuteri RC-14 (2.5*109 CFU each) on the
microbiota and host response. The probiotic treatment did not result in an
improved Nugent score when compared to when placebo. Analysis using 16S rRNA
sequencing and metabolomics profiling revealed that the relative abundance of
Lactobacillus was increased following probiotic administration as compared to
placebo, which was weakly associated with an increase in lactate levels. A
decrease in Atopobium was also observed. Analysis of host responses by microarray
showed the probiotics had an immune-modulatory response including effects on
pattern recognition receptors such as TLR2 while also affecting epithelial
barrier function. This is the first study to use an interactomic approach for the
study of vaginal probiotic administration in post-menopausal women. It shows that
in some cases multifaceted approaches are required to detect the subtle molecular
changes induced by the host to instillation of probiotic strains. TRIAL
REGISTRATION: ClinicalTrials.gov NCT02139839.
PMID- 25127243
TI - Prevention of invasive pneumococcal diseases: beyond cultures.
PMID- 25127241
TI - Integrating transcriptomics with metabolic modeling predicts biomarkers and drug
targets for Alzheimer's disease.
AB - Accumulating evidence links numerous abnormalities in cerebral metabolism with
the progression of Alzheimer's disease (AD), beginning in its early stages. Here,
we integrate transcriptomic data from AD patients with a genome-scale
computational human metabolic model to characterize the altered metabolism in AD,
and employ state-of-the-art metabolic modelling methods to predict metabolic
biomarkers and drug targets in AD. The metabolic descriptions derived are first
tested and validated on a large scale versus existing AD proteomics and
metabolomics data. Our analysis shows a significant decrease in the activity of
several key metabolic pathways, including the carnitine shuttle, folate
metabolism and mitochondrial transport. We predict several metabolic biomarkers
of AD progression in the blood and the CSF, including succinate and prostaglandin
D2. Vitamin D and steroid metabolism pathways are enriched with predicted drug
targets that could mitigate the metabolic alterations observed. Taken together,
this study provides the first network wide view of the metabolic alterations
associated with AD progression. Most importantly, it offers a cohort of new
metabolic leads for the diagnosis of AD and its treatment.
PMID- 25127245
TI - A lightweight distributed framework for computational offloading in mobile cloud
computing.
AB - The latest developments in mobile computing technology have enabled intensive
applications on the modern Smartphones. However, such applications are still
constrained by limitations in processing potentials, storage capacity and battery
lifetime of the Smart Mobile Devices (SMDs). Therefore, Mobile Cloud Computing
(MCC) leverages the application processing services of computational clouds for
mitigating resources limitations in SMDs. Currently, a number of computational
offloading frameworks are proposed for MCC wherein the intensive components of
the application are outsourced to computational clouds. Nevertheless, such
frameworks focus on runtime partitioning of the application for computational
offloading, which is time consuming and resources intensive. The resource
constraint nature of SMDs require lightweight procedures for leveraging
computational clouds. Therefore, this paper presents a lightweight framework
which focuses on minimizing additional resources utilization in computational
offloading for MCC. The framework employs features of centralized monitoring,
high availability and on demand access services of computational clouds for
computational offloading. As a result, the turnaround time and execution cost of
the application are reduced. The framework is evaluated by testing prototype
application in the real MCC environment. The lightweight nature of the proposed
framework is validated by employing computational offloading for the proposed
framework and the latest existing frameworks. Analysis shows that by employing
the proposed framework for computational offloading, the size of data
transmission is reduced by 91%, energy consumption cost is minimized by 81% and
turnaround time of the application is decreased by 83.5% as compared to the
existing offloading frameworks. Hence, the proposed framework minimizes
additional resources utilization and therefore offers lightweight solution for
computational offloading in MCC.
PMID- 25127244
TI - Vaccine effectiveness of the pneumococcal Haemophilus influenzae protein D
conjugate vaccine (PHiD-CV10) against clinically suspected invasive pneumococcal
disease: a cluster-randomised trial.
AB - BACKGROUND: Vaccine effectiveness of pneumococcal conjugate vaccines against
culture-confirmed invasive pneumococcal disease has been well documented. In the
Finnish Invasive Pneumococcal disease (FinIP) trial, we reported vaccine
effectiveness and absolute rate reduction against laboratory-confirmed invasive
pneumococcal disease (confirmation by culture or antigen or DNA detection
irrespective of serotype). Here, we assessed vaccine effectiveness of PHiD-CV10
against clinically suspected invasive pneumococcal disease in children by use of
diagnoses coded in hospital discharge registers. METHODS: For this phase 3/4
cluster-randomised, double-blind trial, undertaken between Feb 18, 2009, and Dec
31, 2011, in municipal health-care centres and the Tampere University Vaccine
Research Centre (Finland), we randomly assigned (2:2:1:1) 78 clusters into PHiD
CV10 three plus one, PHiD-CV10 two plus one, control three plus one, control two
plus one groups (26:26:13:13 clusters) to give PHiD-CV10 in either three plus one
or two plus one schedule (if enrolled before 7 months of age; infant schedules),
two plus one (if enrolled between 7 and 11 months; catch-up schedules), and two
doses at least 6 months apart (if enrolled between 12 and 18 months; catch-up
schedules). Children were eligible if they had not received and were not
anticipated to receive any of the study vaccines and had no general
contraindications to vaccinations. We collected all inpatient and outpatient
discharge notifications from the national hospital discharge register with
International Classification of Diseases (ICD) 10 diagnoses compatible with
invasive pneumococcal disease or unspecified sepsis, and verified data with
patient files. We excluded invasive pneumococcal disease cases confirmed by
positive culture or DNA/RNA detection from normally sterile body fluid. The
primary objective was to estimate vaccine effectiveness against all register
based non-laboratory-confirmed invasive pneumococcal disease or unspecified
sepsis and patient-file verified non-laboratory-confirmed invasive pneumococcal
disease in infants younger than 7 months at enrolment. Masked follow-up lasted
from the date of the first vaccination to Dec 31, 2011. Vaccine effectiveness was
calculated against all episodes. This trial is registered with
ClinicalTrials.gov, numbers NCT00861380 and NCT00839254. FINDINGS: We enrolled
47,366 children. On the basis of ICD-10 diagnoses, we recorded 264 episodes of
register-based non-laboratory-confirmed invasive pneumococcal disease or
unspecified sepsis, of which 102 were patient-file verified non-laboratory
confirmed invasive pneumococcal disease. The vaccine effectiveness was 50% (95%
CI 32-63) in the 30,527 infants with three plus one and two plus one schedules
combined and the absolute incidence rate reduction was 207 episodes per 100,000
person-years (95% CI 127-286). The vaccine effectiveness against the patient-file
verified non-laboratory-confirmed invasive pneumococcal disease was 71% (95% CI
52-83) in infant three plus one and two plus one schedules combined. The absolute
rate reduction was 142 episodes per 100,000 person-years (95% CI 91-191) in
infant cohorts. INTERPRETATION: This vaccine-probe analysis is the first report
showing the effect of pneumococcal conjugate vaccines on clinically suspected
invasive pneumococcal disease. The absolute rate reduction was markedly higher
compared with laboratory-confirmed invasive pneumococcal disease, which implies
low sensitivity of the laboratory-based case definitions and subsequently higher
public health effect of pneumococcal conjugate vaccines against invasive
pneumococcal disease than previously estimated. FUNDING: GlaxoSmithKline
Biologicals SA and National Institute for Health and Welfare (THL), Finland.
PMID- 25127246
TI - The use of social networking services and their relationship with the big five
personality model and job satisfaction in Korea.
AB - Social networking services (SNSs) have been garnering attention from society due
to their recent rapid growth. This study examines whether SNS use can affect the
relationship between the Big Five personality model and individual job
satisfaction. Based on a sample of 1,452 workers in Korea, the results of this
study indicate that the Big Five personality model (extroversion, agreeableness,
and neuroticism) was significantly related to individual job satisfaction.
Further, SNS use moderated the relationship between extroversion and neuroticism
with individual job satisfaction. Also, SNS use was found to increase job
satisfaction of Korean workers who are more extroverted, while it also affected
job satisfaction of Korean workers with low agreeableness. As SNS use plays an
important role in the workplace, it is necessary to realize and appreciate the
importance of SNSs in shaping and promoting job satisfaction of working
individuals.
PMID- 25127247
TI - A method for predicting the number of active bubbles in sonochemical reactors.
AB - Knowledge of the number of active bubbles in acoustic cavitation field is very
important for the prediction of the performance of ultrasonic reactors toward
most chemical processes induced by ultrasound. The literature in this field is
scarce, probably due to the complicated nature of the phenomena. We introduce
here a relatively simple semi-empirical method for predicting the number of
active bubbles in an acoustic cavitation field. By coupling the bubble dynamics
in an acoustical field with chemical kinetics occurring in the bubble during
oscillation, the amount of the radical species OH and HO2 and molecular H2O2
released by a single bubble was estimated. Knowing that the H2O2 measured
experimentally during sonication of water comes from the recombination of
hydroxyl (OH) and perhydroxyl (HO2) radicals in the liquid phase and assuming
that in sonochemistry applications, the cavitation is transient and the bubble
fragments at the first collapse, the number of bubbles formed per unit time per
unit volume is then easily determined using material balances for H2O2, OH and
HO2 in the liquid phase. The effect of ultrasonic frequency on the number of
active bubbles was examined. It was shown that increasing ultrasonic frequency
leads to a substantial increase in the number of bubbles formed in the reactor.
PMID- 25127248
TI - Effect of citric acid induced deflocculation on the ultrasonic pretreatment
efficiency of dairy waste activated sludge.
AB - In this investigation, the application of citric acid was explored for the
removal of extracellular polymeric substance (EPS) from waste activated sludge
(WAS), followed by ultrasonic pretreatment, which enhanced the subsequent
anaerobic biodegradability. EPS was removed with 0.05g/g SS of citric acid. The
chemical oxygen demand (COD) solubilization and suspended solids (SS) reduction
that occurred for specific energy input of 171.9kJ/kg TS, in deflocculated (EPS
removed and ultrasonically pretreated) sludges were found to be 22.70% and 20.28%
and was comparatively higher, than the flocculated (with EPS and ultrasonically
pretreated). The biogas yield potential of flocculated and deflocculated sludges
(specific energy input - 171.9kJ/kgTS) was found to be 0.212L/(gVS) and
0.435L/(gVS), respectively. Accordingly, the deflocculation and ultrasonic
pretreatment improved the anaerobic biodegradability efficiently. Thus, this
chemo mediated sonic pretreatment is an effective method for enhancing
biodegradability and improving clean energy generation from WAS.
PMID- 25127249
TI - Colonization of later life? Laypersons' and users' agency regarding anti-aging
medicine in Germany.
AB - Anti-aging medicine is regarded as a significant trend in contemporary Western
societies. Foucauldian gerontology provides some of the dominant theoretical
perspectives on this trend in social and cultural theory. Proceeding from its
interpretation and critique of anti-aging in terms of medicalization and
responsibilization of aging, we explore by means of qualitative socio-empirical
research how interested laypersons as well as non-professional users in the
German context actually perceive of and deal with the medical claims and moral
imperatives surrounding anti-aging medicine. The study is based on 12 focus
groups and 20 narrative interviews (96 participants all included). They were
conducted in Germany between 2011 and 2012, and analyzed by qualitative content
analysis as well as comparative sequence analysis. The empirical findings
indicate that in everyday life, interested laypersons and non-professional users
employ different strategies for dealing with anti-aging products and services,
corresponding to different degrees of affirmation and rejection. Four strategies
could be identified: (a) medical optimism, (b) preventive maximalism, (c)
ritualized well-being, and (d) considerate rejection. Also, each type was
problematized and arguments against it were expressed. Overall, these findings
show how our participants develop viable strategies to put the relevance of
medical knowledge and moral imperatives for their own lives into perspective.
This sheds light on laypersons' and users' agency-that is, their active role and
deliberative space in the uptake, adaptation, and integration of anti-aging into
their personal life. These empirical findings contribute to an enriched picture
of the actual practice of anti-aging in concrete national and socio-cultural
settings. This can help to differentiate the evaluation and thus make its
critique more context sensitive, adequate, and targeted.
PMID- 25127250
TI - Cognitive functioning among patients with diabetic foot.
AB - AIMS: Using diabetic foot (DF) as an indicator of severe diabetes, we aimed to
investigate the cognitive profile of DF patients and the relations between
cognitive functioning and both diabetes complications and comorbidities. METHODS:
Dementia-free patients with DF aged 30-90 (n=153) were assessed through medical
records and a cognitive battery. Information on diabetes complications and
comorbidities was collected via interview; glycated hemoglobin (HbA1c) was
tested. Data were analyzed using robust logistic or quantile regression adjusted
for potential confounders. RESULTS: The mean Mini-Mental Examination (MMSE) score
of patients was 24.6 (SD=3.6), and 40% had global cognitive dysfunction (MMSE
<=24). Among elderly patients (aged >=65), MMSE impairment was related to
amputation (OR 3.59, 95% CI 1.07-12.11). Episodic memory impairment was
associated with foot amputation (OR 4.13, 95% CI 1.11-15.28) and microvascular
complications (OR 9.68, 95% CI 1.67-56.06). Further, elderly patients with HbA1c
<7% had increased odds of psychomotor slowness (OR 7.75, 95% CI 1.55-38.73) and
abstract reasoning impairment (OR 4.49, 95% CI: 1.15-17.46). However, such
significant associations were not shown in adult patients aged <65. CONCLUSION:
Amputation, microvascular diseases and glycemic control were associated with
impaired global cognitive function and its domains among patients aged >=65.
PMID- 25127251
TI - A cluster randomized-controlled trial of a classroom-based drama workshop program
to improve mental health outcomes among immigrant and refugee youth in special
classes.
AB - OBJECTIVES: The aim of this cluster randomized trial was to evaluate the
effectiveness of a school-based theatre intervention program for immigrant and
refugee youth in special classes for improving mental health and academic
outcomes. The primary hypothesis was that students in the theatre intervention
group would report a greater reduction in impairment from symptoms compared to
students in the control and tutoring groups. METHODS: Special classrooms in five
multiethnic high schools were randomly assigned to theater intervention (n = 10),
tutoring (n = 10) or control status (n = 9), for a total of 477 participants.
Students and teachers were non-blinded to group assignment. The primary outcome
was impairment from emotional and behavioural symptoms assessed by the Impact
Supplement of the Strengths and Difficulties Questionnaire (SDQ) completed by the
adolescents. The secondary outcomes were the SDQ global scores (teacher and youth
reports), impairment assessed by teachers and school performance. The effect of
the interventions was assessed through linear mixed effect models which
incorporate the correlation between students in the same class, due to the nature
of the randomization of the interventions by classroom. RESULTS: The theatre
intervention was not associated with a greater reduction in self-reported
impairment and symptoms in youth placed in special class because of learning,
emotional and behavioural difficulties than a tutoring intervention or a non
active control group. The estimates of the different models show a non
significant decrease in both self-reported and impairment scores in the theatre
intervention group for the overall group, but the impairment score decreased
significantly for first generation adolescents while it increased for second
generation adolescents. CONCLUSION: The difference between the population of
immigrant and refugee youth newcomers studied previously and the sample of this
trial may explain some of the differences in the observed impact of the theatre
intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT01426451.
PMID- 25127252
TI - Potentially inappropriate medication use in older people with cancer: prevalence
and correlates.
AB - OBJECTIVES: Potentially inappropriate medication (PIM) use has been associated
with an increase in adverse drug events, hospitalization and mortality. This
study investigated the prevalence and factors associated with PIM use in patients
presenting to a medical oncology outpatient clinic. MATERIALS AND METHODS:
Consecutive patients (n=385) aged >= 70 years referred to a medical oncology
outpatient clinic between January 2009 and July 2010 completed a structured data
collection instrument. The instrument assessed medication use, diagnoses, self
reported falls in the previous six months, pain (10-point visual analog scale
[VAS]) and distress (10-point VAS). Frailty was defined using exhaustion, weight
loss, Karnofsky Performance Scale, instrumental activities of daily living and
physical function. PIM use was defined by the Beers Criteria. Logistic regression
was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for
factors associated with PIM use. RESULTS: In total, 26.5% (n=102) of the sample
used >=1 PIM. The five most prevalent classes of PIMs were benzodiazepines (n=34,
8.8%), tricyclic antidepressants (n=16, 4.2%), alpha-adrenoreceptor antagonists
(prazosin) (n=15, 3.9%), propulsives (metoclopramide) (n=15, 3.9%) and non
steroidal anti-inflammatory drugs (n=14, 3.6%). In multivariate analyses, PIM use
was associated with age 75-79 years (OR 1.83; 95%CI 1.02-3.26) compared to age 70
74 years, using >= 5 medications (OR 4.10; 95%CI 2.26-7.44) compared to <5
medications and being frail (OR 3.05; 95%CI 1.18-7.87) compared to being robust.
CONCLUSION: More than one quarter of older people with cancer used one or more
PIMs, and this was associated with being frail compared to being robust.
PMID- 25127253
TI - Fecal carriage rates of extended-spectrum beta-lactamase-producing Escherichia
coli among antibiotic naive healthy human volunteers.
AB - INTRODUCTION: Higher prevalence of extended-spectrum beta-lactamase (ESBL)
producing Escherichia coli fecal carriage has been reported in the nosocomial
setting than in the community. We tried to determine the fecal carriage of ESBL
producing E. coli among healthy volunteers in a relatively isolated community.
MATERIALS AND METHODS: This study was conducted on 115 healthy adult volunteers
from whom one fecal sample was collected and was plated on selective media. Each
morphotypes were identified, characterized, and ESBL phenotype was confirmed by
double-disk potentiation method. Molecular characterization of ESBL gene was done
using multiplex polymerase chain reaction and pulse-field gel electrophoresis
(PFGE) was done to identify their clonal relation. RESULTS: ESBL-producing E.
coli had a prevalence of 19% (22/115) among the healthy volunteers in the
community. CTX-M was the predominant type, showed a presence 95.5% (21/22), TEM
63%, SHV 9%, and both TEM and CTX-M were present in 63.6% (14/22), all three
present in 4.5% (1/22). The lineage using PFGE showed a single clone in 17
isolates. Seven isolates were type A (all TEM & CTX-M), six were type A1 (all TEM
& CTX-M except 2), four were type A2 (all CTX-M), and three belonged to types B,
C, and D respectively Conclusion: High prevalence rate of 19% in the community
indicated by this study implies the possibility of sustained ESBL carriage even
among isolated population, which could serve as a reservoir for enriching the
ESBL pool in the hospital. Clonal relations also indicate a possible
epidemiological source that needs to be evaluated.
PMID- 25127254
TI - Epidemiological investigation of bovine tuberculosis herd breakdowns in Spain
2009/2011.
AB - We analyzed the most likely cause of 687 bovine tuberculosis (bTB) breakdowns
detected in Spain between 2009 and 2011 (i.e., 22% of the total number of
breakdowns detected during this period). Seven possible causes were considered:
i) residual infection; ii) introduction of infected cattle from other herds; iii)
sharing of pastures with infected herds; iv) contiguous spread from infected
neighbor herds; v) presence of infected goats in the farm; vi) interaction with
wildlife reservoirs and vii) contact with an infected human. For each possible
cause a decision tree was developed and key questions were included in each of
them. Answers to these key questions lead to different events within each
decision tree. In order to assess the likelihood of occurrence of the different
events a qualitative risk assessment approach was used. For this purpose, an
expert opinion workshop was organized and ordinal values, ranging from 0 to 9
(i.e., null to very high likelihood of occurrence) were assigned. The analysis
identified residual infection as the most frequent cause of bTB breakdowns
(22.3%; 95%CI: 19.4-25.6), followed by interaction with wildlife reservoirs
(13.1%; 95%CI: 10.8-15.8). The introduction of infected cattle, sharing of
pastures and contiguous spread from infected neighbour herds were also identified
as relevant causes. In 41.6% (95%CI: 38.0-45.4) of the breakdowns the origin of
infection remained unknown. Veterinary officers conducting bTB breakdown
investigations have to state their opinion about the possible cause of each
breakdown. Comparison between the results of our analysis and the opinion from
veterinary officers revealed a slight concordance. This slight agreement might
reflect a lack of harmonized criteria to assess the most likely cause of bTB
breakdowns as well as different perceptions about the importance of the possible
causes. This is especially relevant in the case of the role of wildlife
reservoirs.
PMID- 25127255
TI - Diversity of bacteria carried by pinewood nematode in USA and phylogenetic
comparison with isolates from other countries.
AB - Pine wilt disease (PWD) is native to North America and has spread to Asia and
Europe. Lately, mutualistic relationship has been suggested between the pinewood
nematode (PWN), Bursaphelenchus xylophilus the causal nematode agent of PWD, and
bacteria. In countries where PWN occurs, nematodes from diseased trees were
reported to carry bacteria from several genera. However no data exists for the
United States. The objective of this study was to evaluate the diversity of the
bacterial community carried by B. xylophilus, isolated from different Pinus spp.
with PWD in Nebraska, United States. The bacteria carried by PWN belonged to
Gammaproteobacteria (79.9%), Betaproteobacteria (11.7%), Bacilli (5.0%),
Alphaproteobacteria (1.7%) and Flavobacteriia (1.7%). Strains from the genera
Chryseobacterium and Pigmentiphaga were found associated with the nematode for
the first time. These results were compared to results from similar studies
conducted from other countries of three continents in order to assess the
diversity of bacteria with associated with PWN. The isolates from the United
States, Portugal and China belonged to 25 different genera and only strains from
the genus Pseudomonas were found in nematodes from all countries. The strains
from China were closely related to P. fluorescens and the strains isolated from
Portugal and USA were phylogenetically related to P. mohnii and P. lutea.
Nematodes from the different countries are associated with bacteria of different
species, not supporting a relationship between PWN with a particular bacterial
species. Moreover, the diversity of the bacteria carried by the pinewood nematode
seems to be related to the geographic area and the Pinus species. The roles these
bacteria play within the pine trees or when associated with the nematodes, might
be independent of the presence of the nematode in the tree and only related on
the bacteria's relationship with the tree.
PMID- 25127256
TI - The X gene of adeno-associated virus 2 (AAV2) is involved in viral DNA
replication.
AB - Adeno-associated virus (AAV) (type 2) is a popular human gene therapy vector with
a long active transgene expression period and no reported vector-induced adverse
reactions. Yet the basic molecular biology of this virus has not been fully
addressed. One potential gene at the far 3' end of the AAV2 genome, previously
referred to as X (nt 3929 to 4393), overlapping the 3' end of the cap gene, has
never been characterized, although we did previously identify a promoter just up
stream (p81). Computer analysis suggested that X was involved in replication and
transcription. The X protein was identified during active AAV2 replication using
a polyclonal antibody against a peptide starting at amino acid 98. Reagents for
the study of X included an AAV2 deletion mutant (dl78-91), a triple nucleotide
substitution mutant that destroys all three 5' AUG-initiation products of X, with
no effect on the cap coding sequence, and X-positive-293 cell lines. Here, we
found that X up-regulated AAV2 DNA replication in differentiating keratinocytes
(without helper virus, autonomous replication) and in various forms of 293 cell
based assays with help from wild type adenovirus type 5 (wt Ad5) or Ad5 helper
plasmid (pHelper). The strongest contribution by X was seen in increasing wt AAV2
DNA replication in keratinocytes and dl78-91 in Ad5-infected X-positive-293 cell
lines (both having multi-fold effects). Mutating the X gene in pAAV-RC (pAAV-RC
3Xneg) yielded approximately a ~33% reduction in recombinant AAV vector DNA
replication and virion production, but a larger effect was seen when using this
same X-knockout AAV helper plasmid in X-positive-293 cell lines versus normal 293
cells (again, multi-fold). Taken together these data strongly suggest that AAV2 X
encodes a protein involved in the AAV life cycle, particularly in increasing AAV2
DNA replication, and suggests that further studies are warranted.
PMID- 25127257
TI - Quantifying age-related rates of social contact using diaries in a rural coastal
population of Kenya.
AB - BACKGROUND: Improved understanding and quantification of social contact patterns
that govern the transmission dynamics of respiratory viral infections has utility
in the design of preventative and control measures such as vaccination and social
distancing. The objective of this study was to quantify an age-specific matrix of
contact rates for a predominantly rural low-income population that would support
transmission dynamic modeling of respiratory viruses. METHODS AND FINDINGS: From
the population register of the Kilifi Health and Demographic Surveillance System,
coastal Kenya, 150 individuals per age group (<1, 1-5, 6-15, 16-19, 20-49, 50 and
above, in years) were selected by stratified random sampling and requested to
complete a day long paper diary of physical contacts (e.g. touch or embrace). The
sample was stratified by residence (rural-to-semiurban), month (August 2011 to
January 2012, spanning seasonal changes in socio-cultural activities), and day of
week. Usable diary responses were obtained from 568 individuals (~50% of
expected). The mean number of contacts per person per day was 17.7 (95% CI 16.7
18.7). Infants reported the lowest contact rates (mean 13.9, 95% CI 12.1-15.7),
while primary school students (6-15 years) reported the highest (mean 20.1, 95%
CI 18.0-22.2). Rates of contact were higher within groups of similar age
(assortative), particularly within the primary school students and adults (20-49
years). Adults and older participants (>50 years) exhibited the highest inter
generational contacts. Rural contact rates were higher than semiurban (18.8 vs
15.6, p = 0.002), with rural primary school students having twice as many
assortative contacts as their semiurban peers. CONCLUSIONS AND SIGNIFICANCE: This
is the first age-specific contact matrix to be defined for tropical Sub-Saharan
Africa and has utility in age-structured models to assess the potential impact of
interventions for directly transmitted respiratory infections.
PMID- 25127258
TI - Glucose rapidly induces different forms of excitatory synaptic plasticity in
hypothalamic POMC neurons.
AB - Hypothalamic POMC neurons are required for glucose and energy homeostasis. POMC
neurons have a wide synaptic connection with neurons both within and outside the
hypothalamus, and their activity is controlled by a balance between excitatory
and inhibitory synaptic inputs. Brain glucose-sensing plays an essential role in
the maintenance of normal body weight and metabolism; however, the effect of
glucose on synaptic transmission in POMC neurons is largely unknown. Here we
identified three types of POMC neurons (EPSC(+), EPSC(-), and EPSC(+/-)) based on
their glucose-regulated spontaneous excitatory postsynaptic currents (sEPSCs),
using whole-cell patch-clamp recordings. Lowering extracellular glucose decreased
the frequency of sEPSCs in EPSC(+) neurons, but increased it in EPSC(-) neurons.
Unlike EPSC(+) and EPSC(-) neurons, EPSC(+/-) neurons displayed a bi-phasic sEPSC
response to glucoprivation. In the first phase of glucoprivation, both the
frequency and the amplitude of sEPSCs decreased, whereas in the second phase,
they increased progressively to the levels above the baseline values.
Accordingly, lowering glucose exerted a bi-phasic effect on spontaneous action
potentials in EPSC(+/-) neurons. Glucoprivation decreased firing rates in the
first phase, but increased them in the second phase. These data indicate that
glucose induces distinct excitatory synaptic plasticity in different
subpopulations of POMC neurons. This synaptic remodeling is likely to regulate
the sensitivity of the melanocortin system to neuronal and hormonal signals.
PMID- 25127260
TI - Ipilimumab treatment associated pituitary hypophysitis: clinical presentation and
imaging diagnosis.
AB - Ipilimumab is an immunomodulating drug for use in treatment of unresectable or
metastatic melanoma with autoimmune lymphocytic hypophysitis as a reported
complication. We describe three recent cases of ipilimumab associated autoimmune
hypophysitis (IAH) at our institution, and provide a selected literature review
showing its variable clinical presentation, imaging appearance and treatment in
order to expedite early and appropriate IAH management. Patients had variable
clinical presentation of hypophysitis, including headache, fatigue, visual
changes, endocrinopathy, and/or hyponatremia. Contrast enhanced MRI showed
symmetric pituitary gland and stalk enlargement in all of our cases and received
a presumptive diagnosis of IAH. Following cessation of therapy and treatment
there was normalization of pituitary morphology at follow-up MRI and return to
clinical baseline. Varying clinical presentation can complicate the diagnosis of
lymphocytic hypophysitis. One must be cognizant of its overall clinical and
radiologic picture in patients receiving ipilimumab, now commonly used for the
treatment of metastatic melanoma.
PMID- 25127259
TI - Expression of stemness genes in primary breast cancer tissues: the role of SOX2
as a prognostic marker for detection of early recurrence.
AB - The events leading to breast cancer (BC) progression or recurrence are not
completely understood and new prognostic markers aiming at identifying high risk
patients and to develop suitable therapy are highly demanded. Experimental
evidences found in cancer cells a deregulated expression of some genes involved
in governance of stem cell properties and demonstrated a relationship between
stemness genes overexpression and poorly differentiated BC subtypes. In the
present study 140 primary invasive BC specimens were collected. The expression
profiles of 13 genes belonging to the OCT3/SOX2/NANOG/KLF4 core circuitry by RT
PCR were analyzed and any correlation between their expression and the BC clinic
pathological features (CPfs) and prognosis was investigated. In our cohort (117
samples), NANOG, GDF3 and SOX2 significantly correlated with grade 2, Nodes
negative status and higher KI67 proliferation index, respectively (p=0.019,
p=0.029, p= 0.035). According to multivariate analysis, SOX2 expression resulted
independently associated with increased risk of recurrence (HR= 2,99; p= p=0,004)
as well as Nodes status (HR=2,44; p=0,009) and T-size >1 (HR=1,77; p=0,035). Our
study provides further proof of the suitable use of stemness genes in BC
management. Interestingly, a prognostic role of SOX2, which seems to be a
suitable marker of early recurrence irrespective of other clinicopathological
features.
PMID- 25127261
TI - Ventriculomammary shunt: an unusual ventriculoperitoneal shunt complication.
AB - Ventriculoperitoneal (VP) shunt malfunctions are common and can result in
significant consequences for patients. Despite the prevalence of breast
augmentation surgery and breast surgery for other pathologies, few breast related
VP shunt complications have been reported. A 54-year-old woman with hydrocephalus
post-subarachnoid hemorrhage returned 1 month after VP shunt placement
complaining of painful unilateral breast enlargement. After investigation, it was
determined that the distal VP shunt catheter had migrated from the peritoneal
cavity into the breast and wrapped around her breast implant. The breast
enlargement was the result of cerebrospinal fluid retention. We detail this
unusual case and review all breast related VP shunt complications reported in the
literature. To avoid breast related complications related to VP shunt procedures,
it is important to illicit pre-procedural history regarding breast implants,
evade indwelling implants during catheter tunneling and carefully securing the
abdominal catheter to prevent retrograde catheter migration to the breast.
PMID- 25127262
TI - Identification of crypto- and neochlorogenic lactones as potent xanthine oxidase
inhibitors in roasted coffee beans.
AB - Xanthine oxidase (XO) inhibitory activity has been found in boiling water
extracts from roasted coffee beans. Therefore, assay-guided purification of the
extracts was performed using size-exclusion column chromatography, and
subsequently with reversed phase HPLC to afford lactone derivatives of
chlorogenic acids. Among the tested lactones, crypto- and neochlorogenic lactones
showed potent XO inhibitory activities compared with three major chlorogenic
acids found in coffee beans. These XO inhibitory lactones may ameliorate gout and
hyperuricemia in humans who drink coffee.
PMID- 25127263
TI - Making sense of the undue burden interpretation of minimal risk.
PMID- 25127264
TI - On the minimal risk threshold in research with children.
AB - To protect children in research, procedures that are not administered in the
medical interests of a child must be restricted. The risk threshold for these
procedures is generally measured according to the concept of minimal risk.
Minimal risk is often defined according to the risks of "daily life." But it is
not clear whose daily life should serve as the baseline; that is, it is not clear
to whom minimal risk should refer. Commentators in research ethics often argue
that "minimal risk" should refer to healthy children or the subjects of the
research. I argue that neither of these interpretations is successful. I propose
a new interpretation in which minimal risk refers to children who are not unduly
burdened by their daily lives. I argue that children are not unduly burdened when
they fare well, and I defend a substantive goods account of children's welfare.
PMID- 25127265
TI - Justice and nontherapeutic pediatric research.
PMID- 25127266
TI - Defining minimal risk and the clinical disconnect.
PMID- 25127267
TI - Using the minimal risk threshold for all "no-benefit" pediatric studies.
PMID- 25127268
TI - Standards for an account of children's well-being.
PMID- 25127269
TI - Using the lives of children who are thriving as a baseline for minimal risk is
not useful for IRB determinations.
PMID- 25127270
TI - On the minimal risk threshold in research with children: "substantive goods" and
other criteria.
PMID- 25127271
TI - Disability, health, and minimal risk thresholds.
PMID- 25127272
TI - Undue burden: looking at minimal risk and the material principle of justice.
PMID- 25127273
TI - Addressing dual agency: getting specific about the expectations of
professionalism.
AB - Professionalism requires that physicians uphold the best interests of patients
while simultaneously insuring just use of health care resources. Current
articulations of these obligations like the American Board of Internal Medicine
(ABIM) Foundation's Physician Charter do not reconcile how these obligations fit
together when they conflict. This is the problem of dual agency. The most common
ways of dealing with dual agency: "bunkering"--physicians act as though societal
cost issues are not their problem; "bailing"--physicians assume that they are
merely agents of society and deliver care typically based on a strongly
consequentialist public health ethic; or "balancing"--a vaguely specified attempt
to uphold both patient welfare and societal need for judicious resource use
simultaneously--all fail. Here I propose how the problem of dual agency might
begin to be addressed with rigor and consistency. Without dealing with the dual
agency problem and getting more specific about how to reconcile its norms when
they conflict, the expectations of professionalism risk being written off as
cute, nonbinding aphorisms from the medical profession.
PMID- 25127274
TI - Agency is messy: get used to it.
PMID- 25127275
TI - When professional obligations collide: context matters.
PMID- 25127276
TI - Legal barriers to physicians' stewardship role.
PMID- 25127277
TI - In defense of bunkering.
PMID- 25127278
TI - Dual agency and role morality.
PMID- 25127279
TI - Getting even more specific about physicians' obligations: justice,
responsibility, and professionalism.
PMID- 25127280
TI - A mask tells us more than a face.
PMID- 25127281
TI - Physicians' dual agency, stewardship, and marginally beneficial care.
PMID- 25127282
TI - Political activism is not mandated by medical professionalism.
PMID- 25127284
TI - Sox2 is a potent inhibitor of osteogenic and adipogenic differentiation in human
mesenchymal stem cells.
AB - Human mesenchymal stem cells (hMSCs) are a promising target for cell-based bone
regeneration. However, their application for clinical use is limited because
hMSCs lose their ability for cell division and differentiation during longer in
vitro cultivation. The osteogenic differentiation is regulated through a complex
network of molecular signal transduction pathways where the canonical Wnt pathway
plays an important role. Sox2, a known key factor for maintenance of cellular
pluripotency in stem cells, is supposed to influence the Wnt pathway in
osteoblasts. In this study, we overexpressed Sox2 in immortalized hMSCs by
lentiviral gene transfer. Sox2 overexpression significantly reduced the
osteogenic and adipogenic differentiation potentials. This effect was abolished
by knockdown of Sox2 overexpression. In addition, Oct4 and Nanog, other key
transcription factors for pluripotency, are strongly upregulated when Sox2 is
overexpressed. Furthermore, Dkk1, a target gene of the Sox2-Oct4 heterodimer and
a Wnt antagonist, is downregulated. Sox2 overexpression causes higher expression
levels of beta-catenin, the central transcription factor of the canonical Wnt
pathway. These results suggest that Sox2 keeps hMSCs in an undifferentiated state
by influencing the canonical Wnt pathway. Regulated expression of Sox2 may be a
promising tool to cultivate hMSCs in sufficient quantities for cell and gene
therapy applications.
PMID- 25127283
TI - Local and systemic cytokine expression in patients with postherpetic neuralgia.
AB - BACKGROUND: Postherpetic neuralgia (PHN) is the painful complication of a
varicella zoster virus reactivation. We investigated the systemic and local gene
expression of pro- and anti-inflammatory cytokine expression in patients with
PHN. METHODS: Thirteen patients with PHN at the torso (Th4-S1) were recruited.
Skin punch biopsies were obtained from the painful and the contralateral painless
body area for intraepidermal nerve fiber density (IENFD) and cytokine profiling.
Additionally, blood was withdrawn for systemic cytokine expression and compared
to blood values of healthy controls. We analyzed the gene expression of selected
pro- and anti-inflammatory cytokines (tumor necrosis factor-alpha [TNF] and
interleukins [IL]-1beta, IL-2, and IL-8). RESULTS: IENFD was lower in affected
skin compared to unaffected skin (p<0.05), while local gene expression of pro-
and anti-inflammatory cytokines did not differ except for two patients who had
7fold higher IL-6 and 10fold higher IL-10 gene expression in the affected skin
compared to the contralateral unaffected skin sample. Also, the systemic
expression of cytokines in patients with PHN and in healthy controls was similar.
CONCLUSION: While the systemic and local expression of the investigated pro- and
anti-inflammatory cytokines was not different from controls, this may have been
influenced by study limitations like the low number of patients and different
disease durations. Furthermore, other cytokines or pain mediators need to be
considered.
PMID- 25127287
TI - Gut microbiota in preterm infants with gross blood in stools: A prospective,
controlled study.
AB - OBJECTIVE: Gross blood in stools is a peculiar entity in preterm infants, but
little is known about its etiology. As gut microbiota can be distorted in preterm
infants, we aimed to evaluate the gut microbiota in infants with gross blood in
stools. STUDY DESIGN: In a prospective, controlled, single-center study, we
enrolled all infants born before 34 weeks of gestational age presenting gross
blood in stools that was either completely isolated or associated with mild
clinical symptoms or radiological signs. Each case was paired with two controls
who were hospitalized in the same unit and were matched for gestational age and
birth weight. The diversity of the gut microbiota was analyzed using 16S rRNA
gene PCR and temporal temperature gel electrophoresis. We calculated a diversity
score corresponding to the number of operational taxonomic units present in the
microbiota. RESULTS: Thirty-three preterm infants with gross blood in stools were
matched with 57 controls. Clinical characteristics were similar in cases and
controls. There was no statistically significant difference in the diversity
score between the two groups, but microbiota composition differed. The proportion
of infants with Escherichia coli was significantly higher in cases than in
controls (p=0.045) and the opposite pattern occurred for Staphylococcus sp.
(p=0.047). CONCLUSION: Dysbiosis could be a risk factor for gross blood in stools
in preterm infants. Additional, larger studies are needed to confirm the
implications of the presence of different genotypes of E. coli and to evaluate
preventive actions such as the prophylactic use of probiotics and/or prebiotics.
PMID- 25127289
TI - Measuring behaviors of individual adolescents during group-based substance abuse
intervention.
AB - BACKGROUND: Group treatment is delivered in youth correctional facilities, yet
groups may be iatrogenic. Few measures with demonstrated psychometric properties
exist to track behaviors of individuals during groups. The authors assessed
psychometrics for the Group Process-Individual Level measure (GP-IL) of group
treatment. METHODS: N = 152 teens were randomized to 1 of 2 groups (10 sessions
each). Adolescents, counselors, and observers rated teen behaviors at sessions 3
and 10. GP-IL assesses reinforcement for deviancy and positive behaviors, member
rejection, and counselor connection and praise. RESULTS: Internal consistency and
1-month stability were demonstrated. Concurrent validity is supported by
correlations with measures expected to be associated with group behavior (e.g.,
coping skills). Counselors and observers rated more deviancy during interactive
skills-building groups versus didactic psychoeducational groups (P <= .005).
Scales evidenced incremental validity. CONCLUSIONS: GP-IL offers a sound method
of tracking adolescent behaviors for professionals working with groups.
Counselors ratings were most reliable and valid overall.
PMID- 25127290
TI - Rapid atmospheric pressure plasma jet processed reduced graphene oxide counter
electrodes for dye-sensitized solar cells.
AB - In this work, we present the use of reduced graphene oxide (rGO) as the counter
electrode materials in dye-sensitized solar cells (DSSCs). rGO was first
deposited on a fluorine-doped tin oxide glass substrate by screen-printing,
followed by post-treatment to remove excessive organic additives. We investigated
the effect of atmospheric pressure plasma jet (APPJ) treatment on the DSSC
performance. A power conversion efficiency of 5.19% was reached when DSSCs with
an rGO counter electrode were treated by APPJs in the ambient air for a few
seconds. For comparison, it requires a conventional calcination process at 400
degrees C for 15 min to obtain comparable efficiency. Scanning electron
micrographs show that the APPJ treatment modifies the rGO structure, which may
reduce its conductivity in part but simultaneously greatly enhances its catalytic
activity. Combined with the rapid removal of organic additives by the highly
reactive APPJ, DSSCs with APPJ-treated rGO counter electrode show comparable
efficiencies to furnace-calcined rGO counter electrodes with greatly reduced
process time. This ultrashort process time renders an estimated energy
consumption per unit area of 1.1 kJ/cm(2), which is only one-third of that
consumed in a conventional furnace calcination process. This new methodology thus
saves energy, cost, and time, which is greatly beneficial to future mass
production.
PMID- 25127288
TI - Associations between maternal scaffolding and executive functioning in 3 and 4
year olds born very low birth weight and normal birth weight.
AB - BACKGROUND: Deficits in executive function, including measures of working memory,
inhibition and cognitive flexibility, have been documented in preschoolers born
very low birth weight (VLBW) compared with preschoolers born normal birth weight
(NBW). Maternal verbal scaffolding has been associated with positive outcomes for
both at-risk and typically developing preschoolers. AIMS: The purpose of this
study was to examine associations between maternal verbal scaffolding, Verbal IQ
(VIQ) and executive function measures in preschoolers born VLBW. SUBJECTS: A
total of 64 VLBW and 40 NBW preschoolers ranging in age from 3 1/2 to 4 years
participated in the study. OUTCOME MEASURES: VIQ was measured with the Wechsler
Preschool and Primary Scale of Intelligence - Third Edition. Executive function
tests included the Bear Dragon, Gift Delay Peek, Reverse Categorization and
Dimensional Change Card Sort-Separated Dimensions. STUDY DESIGN: Maternal verbal
scaffolding was coded during a videotaped play session. Associations between
maternal verbal scaffolding and preschoolers' measures of VIQ and executive
function were compared. Covariates included test age, maternal education, and
gender. RESULTS: Preschoolers born VLBW performed significantly worse on VIQ and
all executive function measures compared to those born NBW. Maternal verbal
scaffolding was associated with VIQ for VLBW preschoolers and Gift Delay Peek for
the NBW group. Girls born VLBW outperformed boys born VLBW on VIQ and Bear
Dragon. CONCLUSION: Integrating scaffolding skills training as part of parent
focused intervention may be both feasible and valuable for early verbal reasoning
and EF development.
PMID- 25127292
TI - Carbon nanotube-poly(methyl methacrylate) hybrid films: preparation using
diazonium salt chemistry and mechanical properties.
AB - HYPOTHESIS: The poor miscibility of carbon nanotubes (CNTs) in common organic
solvents and organic monomers requires their modification by suitable functional
(reactive or not) groups prior to their incorporation in thermoplastic polymers.
EXPERIMENTS: Dispersion behavior of carbon nanotubes and mechanical properties of
various CNT-poly(methylmethacrylate) (PMMA) nanocomposites were investigated. We
studied the influence of the surface chemistry through the use of diazonium salts
as an elegant and environmentally friendly platform to provide a suitable
sidewall functionalization by methyl methacrylate functions. We used either a
molecular size functional group through the grafting of
methacryloxypropyltrimethoxysilane or a macromolecular size one, consisting in
PMMA brushes grown by SI-ATRP in order to study the influence of the length of
methacrylate function on the dispersion of CNT in PMMA. FINDINGS: The hardness
and the elastic indentation modulus of all hybrid films were obtained through
nanoindentation measurements and found to increase, using ATRP-modified CNTs,
suggesting a better dispersion of CNTs in PMMA due to optimal inorganic-organic
interactions promoted by the short chains of PMMA.
PMID- 25127291
TI - Oil rich in carotenoids instead of vitamins C and E as a better option to reduce
doxorubicin-induced damage to normal cells of Ehrlich tumor-bearing mice:
hematological, toxicological and histopathological evaluations.
AB - The development of therapeutic strategies to attenuate chemotherapy toxicity
represents an area of great interest in cancer research, and among them is
nutritional therapy based on antioxidants. As research on this topic is still
controversial and scarce, we aim to investigate the effects of antioxidant
supplementation with vitamin C, vitamin E or pequi oil, a carotenoid-rich oil
extracted from pequi (Caryocar brasiliense), on doxorubicin (DX)-induced
oxidative damage to normal cells in Ehrlich solid tumor-bearing mice. Tumor
weight and volume, histopathology, morphometry and immunohistochemistry were used
to assess the treatments' efficacy in containing tumor aggressiveness and
regression, while possible toxicity of treatments was assessed by animals'
weight, morphological analysis of the heart, liver and kidneys, hemogram, and
serum levels of total bilirubin, direct bilirubin, indirect bilirubin, aspartate
aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl
transferase (GGT), alkaline phosphatase, creatinine and urea. Although all the
chemotherapeutic treatments increased internal necrosis area and reduced the
positive Ki-67 cells compared to non-treated tumors, the treatments with pequi
oil provided before tumor inoculation (PTDX) or in continuous and concurrent
administration with doxorubicin (PTPDX) were more effective in containing tumor
growth, besides increasing lymphocyte-dependent immunity and reducing the adverse
side effects associated with DX-induced oxidative damage to normal cells, mainly
the PTDX treatment. Vitamins C and E given before tumor inoculation and
chemotherapy were not successful against doxorubicin-induced cardiotoxicity,
besides increasing doxorubicin-induced nephrotoxicity, indicating that, at least
for doxorubicin, pequi oil instead of vitamins C and E would be the best option
to reduce its adverse effects.
PMID- 25127293
TI - Synthesis and comparison of two poly (methyl methacrylate-b-3
(trimethoxysilyl)propyl methacrylate)/SiO2 hybrids by "grafting-to" approach.
AB - Two copolymer/SiO2 hybrids are prepared by growing SiO2 on the template of well
structured diblock copolymer PMMA-b-PMPS using a "grafting-to" approach. PMMA-b
PMPS is obtained by atom transfer radical polymerization (ATRP) of methyl
methacrylate (PMMA) and 3-(trimethoxysilyl)propyl methacrylate (PMPS) using a
brominated initiator end group termed 1H,1H,2H,2H-heptadecafluoro (F-Br) and a
conventional initiator of ethyl 2-bromoisobutyrate (EBiB), respectively. The
"grafting-to" approach is controlled at HCl for 24h by hydrolysis and
condensation of Si(OCH3)3 groups in PMPS with tetraethyl orthosilicate (TEOS) to
gain both hybrids of F-PMMA-b-PMPS/SiO2 (by F-Br initiator) and E-PMMA-b
PMPS/SiO2 (by EBIB initiator). Comparatively, a little amount of fluorine content
provided by F-Br is able to tighten the size of self-assembled micelles, to
improve wettability and the viscoelasticity of F-PMMA-b-PMPS film due to F-Br
migrating onto the film surface. Therefore, the surface of F-PMMA-b-PMPS film is
sufficiently hydrophobic (99 degrees and Deltaf=2941Hz) than E-PMMA-b-PMPS film
(94 degrees and Deltaf=4820Hz), and the viscoelasticity of the adsorbed layer for
F-PMMA-b-PMPS (DeltaD/Deltaf=-0.112) film is much harder than E-PMMA-b-PMPS/SiO2
(DeltaD/Deltaf=-0.071). On the other hand, the cross-linked silica in PMMA-b
PMPS/SiO2 could also increase water contact angels of films (100-107 degrees )
and decrease the water absorption (Deltaf=704-798Hz). The influence on the
viscoelasticity of the adsorbed layer by the fluorine group is much more obvious
than the cross-linked silica, therefore F-PMMA-b-PMPS/SiO2 (DeltaD/Deltaf=-0.347)
and F-PMMA-b-PMPS (DeltaD/Deltaf=-0.112) films have harder adsorbed layer than E
PMMA-b-PMPS/SiO2 (-0.071) and F-PMMA-b-PMPS films (-0.042). However, compared
with a slightly improvement in thermo stability by F-Br, the cross-linked silica
in PMMA-b-PMPS/SiO2 performs significantly improving thermal decomposition
temperature at 300 degrees C and 350 degrees C.
PMID- 25127294
TI - Self-assembled monolayers of mercaptobenzoic acid and magnetite nanoparticles as
an efficient support for development of tuberculosis genosensor.
AB - In this work, a genosensor for the electrochemical detection of genomic DNA from
Mycobacterium tuberculosis was developed. The biosensor is based on self
assembled monolayers of mercaptobenzoic acid (MBA) and magnetite nanoparticles
(Fe3O4Nps) on bare gold electrode for immobilization of DNA probe. The aim of
this work was the development of a platform based on cysteine-coated magnetic
Fe3O4Nps linked via the carboxylate group from MBA to the work electrode surface
and subsequently to the DNA probe. The probe-genome interaction was evaluated
using a [Fe(CN)6](4-)/[Fe(CN)6](3-) redox pair. Cyclic voltammetry (CV) and
electrochemical impedance spectroscopy (EIS) were used to evaluate the
bioelectrochemical behavior of the sensor. Atomic force microscopy images showed
Fe3O4Nps immobilized across the electrode surface. The interaction of the sensor
with different genome DNA concentrations resulted in changes in the charge
transfer resistance, indicating a possible use for tuberculosis detection at low
concentrations (detection limit of 6ngMUL(-1)).
PMID- 25127295
TI - Catalytic performance of activated carbon supported cobalt catalyst for CO2
reforming of CH4.
AB - Syngas production by CO2 reforming of CH4 in a fixed bed reactor was investigated
over a series of activated carbon (AC) supported Co catalysts as a function of Co
loading (between 15 and 30wt.%) and calcination temperature (Tc=300, 400 or 500
degrees C). The catalytic performance was assessed through CH4 and CO2
conversions and long-term stability. XRD and SEM were used to characterize the
catalysts. It was found that the stability of Co/AC catalysts was strongly
dependent on the Co loading and calcination temperature. For the loadings (25wt.%
for Tc=300 degrees C), stable activities have been achieved. The loading of
excess Co (>wt.% 25) causes negative effects not only on the performance of the
catalysts but also on the support surface properties. In addition, the experiment
showed that ultrasound can enhance and promote dispersion of the active metal on
the carrier, thus improving the catalytic performance of the catalyst. The
catalyst activity can be long-term stably maintained, and no obvious deactivation
has been observed in the first 2700min. After analyzing the characteristics, a
reaction mechanism for CO2 reforming of CH4 over Co/AC catalyst was proposed.
PMID- 25127296
TI - A green one-pot synthesis of Pt/TiO2/Graphene composites and its electro-photo
synergistic catalytic properties for methanol oxidation.
AB - A facile and green one-pot method was used to synthesize Pt/TiO2/Graphene
composites with ethanol as a reducing agent under microwave irradiation. The as
prepared composites were characterized by SEM, TEM, EDX, XPS, XRD and Raman.
Electrocatalytic performance of the Pt/TiO2/GNs composites was investigated by
cyclic voltammetry (CV), chronoamperometric (CA), COad stripping voltammetry and
electrochemical impedance spectrum (EIS). All experimental data have revealed
that TiO2 (P25) not only enhanced the reduction ability of ethanol under
microwave irradiation but also promoted Pt heterogeneous nucleation to form Pt
nanoclusters which are around P25 and loaded on graphene nanosheets (GNs)
surface. Electrochemical experiments showed that Pt/TiO2/GNs had much higher
catalytic activity and stability toward methanol oxidation reaction (MOR) and
better resistance to CO poisoning compared with Pt/GNs and the commercially
available Johnson Matthey 20% Pt/C catalyst (Pt/C-JM). Especially under UV
irradiation with 20min, Pt/TiO2/GNs composites showed an ultrahigh forward peak
current density of 1354mAmg(-1), nearly 2.5 times higher than that of Pt/C-JM,
which indicated that the electrocatalytic and photocatalytic properties of
Pt/TiO2/GNs had been integrated to boost the catalytic performance for MOR.
PMID- 25127297
TI - Role of proprioceptive information to control balance during gait in healthy and
hemiparetic individuals.
AB - Proprioceptive information is important for balance control yet little is known
about how it is used during gait or how a stroke affects its use. The aim of this
study was to evaluate the role of proprioception in controlling balance during
gait in healthy participants and after stroke. Twelve healthy and 9 hemiparetic
participants walked on an instrumented treadmill in a fully lit room, while whole
body, three-dimensional kinematics were quantified. Vibration was applied
continuously or during the stance phase only, on the posterior neck muscles and
triceps surae tendon on the non-dominant/paretic side. Difficulty in maintaining
dynamic and postural balance was evaluated using stabilizing and destabilizing
forces, respectively. Continuous and stance phase vibration of the triceps surae
reduced the difficulty in maintaining both dynamic and postural balance in
healthy participants (p<.05), with a greater distance between the center of
pressure and the limit of the potential base of support, a more backward body
position, and no change in spatio-temporal gait parameters. No effect of neck
muscle vibration was observed on balance (p=.63 and above). None of the vibration
conditions affected balance or gait parameters among stroke participants. The
results confirmed that proprioceptive information was not used to control balance
during gait in stroke participants. The importance of proprioceptive information
may depend on other factors such as walking and visual conditions. Changes in
sensory integration ability likely explain the results after stroke. Further
study is needed to understand the integration of proprioceptive and visual
information to control balance during gait after stroke.
PMID- 25127298
TI - Hydrogen bond disruption in DNA base pairs from (14)C transmutation.
AB - Recent ab initio molecular dynamics simulations have shown that radioactive
carbon does not normally fragment DNA bases when it decays. Motivated by this
finding, density functional theory and Bader analysis have been used to quantify
the effect of C -> N transmutation on hydrogen bonding in DNA base pairs. We find
that (14)C decay has the potential to significantly alter hydrogen bonds in a
variety of ways including direct proton shuttling (thymine and cytosine),
thermally activated proton shuttling (guanine), and hydrogen bond breaking
(cytosine). Transmutation substantially modifies both the absolute and relative
strengths of the hydrogen bonding pattern, and in two instances (adenine and
cytosine), the density at the critical point indicates development of mild
covalent character. Since hydrogen bonding is an important component of Watson
Crick pairing, these (14)C-induced modifications, while infrequent, may trigger
errors in DNA transcription and replication.
PMID- 25127299
TI - Emphysema genetics. Location, location, location!
PMID- 25127300
TI - New asthma biomarkers: shorter telomeres, longer disease?
PMID- 25127301
TI - The child is father of the man?
PMID- 25127302
TI - ICU-acquired weakness, morbidity, and death.
PMID- 25127303
TI - Propensity-matching analysis is not straightforward.
PMID- 25127304
TI - Measuring mucociliary transport and mucus properties in multiple regions of
airway epithelial surfaces helps clarify cystic fibrosis defects.
PMID- 25127305
TI - Improvement of sinus disease in cystic fibrosis with ivacaftor therapy.
PMID- 25127306
TI - In vivo X-ray imaging reveals improved airway surface hydration after a therapy
designed for cystic fibrosis.
PMID- 25127307
TI - Osteopontin and periostin are associated with a 20-year decline of pulmonary
function in patients with asthma.
PMID- 25127308
TI - Insulin resistance, puberty, and nonatopic asthma in adolescent girls.
PMID- 25127309
TI - Asthmatic and normal respiratory epithelial cells respond differently to
mechanical apical stress.
PMID- 25127310
TI - Inhaled antibiotics or inhaled hazard?
PMID- 25127311
TI - Reply: inhaled antibiotics or inhaled hazard?
PMID- 25127312
TI - Small lesion, severe consequences. An intriguing ventilation-perfusion
scintigraphy.
PMID- 25127313
TI - Pulmonary arteriovenous malformations in the setting of pulmonary amyloidosis.
PMID- 25127314
TI - Sleep-disordered breathing in pregnancy.
PMID- 25127315
TI - Hydrogen-bond-dynamics-based switching of conductivity and magnetism: a phase
transition caused by deuterium and electron transfer in a hydrogen-bonded purely
organic conductor crystal.
AB - A hydrogen bond (H-bond) is one of the most fundamental and important noncovalent
interactions in chemistry, biology, physics, and all other molecular sciences.
Especially, the dynamics of a proton or a hydrogen atom in the H-bond has
attracted increasing attention, because it plays a crucial role in (bio)chemical
reactions and some physical properties, such as dielectricity and proton
conductivity. Here we report unprecedented H-bond-dynamics-based switching of
electrical conductivity and magnetism in a H-bonded purely organic conductor
crystal, kappa-D3(Cat-EDT-TTF)2 (abbreviated as kappa-D). This novel crystal
kappa-D, a deuterated analogue of kappa-H3(Cat-EDT-TTF)2 (abbreviated as kappa
H), is composed only of a H-bonded molecular unit, in which two
crystallographically equivalent catechol-fused ethylenedithiotetrathiafulvalene
(Cat-EDT-TTF) skeletons with a +0.5 charge are linked by a symmetric anionic
[O...D...O](-1)-type strong H-bond. Although the deuterated and parent hydrogen
systems, kappa-D and kappa-H, are isostructural paramagnetic semiconductors with
a dimer-Mott-type electronic structure at room temperature (space group: C2/c),
only kappa-D undergoes a phase transition at 185 K, to change to a nonmagnetic
insulator with a charge-ordered electronic structure (space group: P1). The X-ray
crystal structure analysis demonstrates that this dramatic switching of the
electronic structure and physical properties originates from deuterium transfer
or displacement within the H-bond accompanied by electron transfer between the
Cat-EDT-TTF pi-systems, proving that the H-bonded deuterium dynamics and the
conducting TTF pi-electron are cooperatively coupled. Furthermore, the reason why
this unique phase transition occurs only in kappa-D is qualitatively discussed in
terms of the H/D isotope effect on the H-bond geometry and potential energy
curve.
PMID- 25127316
TI - Postpartum Maternal Sleep, Maternal Depressive Symptoms and Self-Perceived Mother
Infant Emotional Relationship.
AB - This study examined the links between maternal sleep, maternal depressive
symptoms, and mothers' perceptions of their emotional relationship with their
infant in a self-recruited sample of mothers. Eighty mothers of infants 3-18
months old completed sleep diaries for 5 consecutive nights, and questionnaires
assessing sleep (Insomnia Severity Index [ISI]), depressive symptom severity
(Edinburgh Postnatal Depression Scale [EPDS]), and perceived mother-infant
relationship (Postpartum Bonding Questionnaire [PBQ] and Maternal Postnatal
Attachment Questionnaire [MPAQ]). Significant correlations, controlling for
depression severity, were found between more disturbed maternal sleep and more
negative maternal perceptions of the mother-infant relationship. Regression
analyses revealed that EPDS showed the strongest association with PBQ, whereas
ISI demonstrated the strongest association with MPAQ. The present study
highlights the importance of deepening and expanding our understanding of the
negative implications of maternal sleep problems.
PMID- 25127317
TI - Belizentrin, a highly bioactive macrocycle from the dinoflagellate Prorocentrum
belizeanum.
AB - Belizentrin (1), a novel 25-membered polyketide-derived macrocycle, was isolated
from cultures of the marine dinoflagellate Prorocentrum belizeanum. This
metabolite is the first member of an unprecedented class of polyunsaturated and
polyhydroxylated macrolactams. The structure of 1 was primarily determined by NMR
and computational methods. Pharmacological assays with cerebellar cells showed
that 1 produces important changes in neuronal network integrity at nanomolar
concentrations.
PMID- 25127319
TI - Potential energy surfaces and quasiclassical trajectory study of the O + H2(+)->
OH(+) + H, OH + H(+) proton and hydrogen atom transfer reactions and isotopic
variants (D2(+), HD(+)).
AB - The rate constants (k; T: 200-900 K) and cross-sections (sigma; Ecol: 0.010-0.50
eV) of the O + H2(+)-> OH(+) + H (1), OH + H(+) (2) reactions, which occur on the
ground (1(2)A'') and first excited (1(2)A') potential energy surfaces (PESs),
respectively, were investigated for the first time, considering also the rate
constants for D2(+) and HD(+). Ab initio multireference configuration interaction
calculations were performed on both barrierless PESs (where the minimum energy
path involves the insertion of the O atom into the middle of the H2(+) bond), and
suitable analytical expressions were developed for the first time and used in
quasiclassical trajectory (QCT) calculations. k(1) ~ 3k(2) independent of the
isotopic variant, k(H2(+)) > k(HD(+)) > k(D2(+)) for , and the intermolecular and
intramolecular isotopic effects are essentially independent of T. Comparison with
the Langevin-Gioumousis-Stevenson (LGS) simple capture model shows that these
results are similar to the QCT ones, especially for ; and the isotopic effects
are coincident with the QCT ones for both reactions. For O + H2(+), sigma(1) ~
3sigma(2) at Ecol<= 0.10 eV, and sigma(1) = 1.5sigma(2) at 0.40 and 0.50 eV. The
larger value of sigma(1(2)A'') with respect to sigma(1(2)A') arises from the
larger value of bmax(1(2)A'') with respect to bmax(1(2)A'), and this results from
the more attractive character of the former PES. Besides, the reaction
probabilities are quite large [0.78-0.98 (1(2)A'') and 0.78-0.93 (1(2)A')], and
the decreasing trend of both cross-sections as Ecol increases arises from the
barrierless character of both PESs. We expect that these results (in particular,
the competition between proton transfer and hydrogen atom transfer) will
encourage experimentalists to carry out investigations on this interesting
reaction.
PMID- 25127318
TI - Hypnosis in Spain (1888-1905): from spectacle to medical treatment of mediumship.
AB - Towards the end of the nineteenth century, some Spanish physicians sought to
legitimize hypnotherapy within medicine. At the same time, hypnotism was being
popularized among the Spanish population through stage hypnosis shows. In order
to extend the use of medical hypnotherapy, some physicians made efforts to
demarcate the therapeutic use of hypnotic suggestion from its application for
recreational purposes, as performed by stage hypnotists. However, in the eyes of
some physicians, the first public session to legitimize hypnotherapy turned out
to be a complete failure due to its similarities with a stage hypnosis
performance. Apart from exploring this kind of hitherto little-known historical
cases, we explore the role of spiritists in legitimizing medical hypnosis. At a
time when Spanish citizens were still reluctant to accept hypnotherapy, the
spiritists sponsored a charitable clinic where treatment using hypnosis was
offered. We conclude that the clinic was effective in promoting the use of
hypnotherapy, both among physicians as clinical practice, and as a medical
treatment for patients from the less privileged classes of Spanish society.
PMID- 25127321
TI - Evaluation of noise reduction methods for sentence recognition by Mandarin
speaking cochlear implant listeners.
AB - OBJECTIVES: The purpose of this study was to (1) assess the contributions of
single-channel noise-reduction (NR) algorithms for improving speech
intelligibility for Mandarin-speaking cochlear implant (CI) listeners and (2)
examine whether different algorithms perform differently in various environmental
noises. DESIGN: Mandarin sentences were corrupted by three types of maskers,
including speech-shaped noise, babble, and car noise, at +10, +5, or 0 dB signal
to noise ratios and processed by four single-channel NR algorithms. The processed
sentences were played to seven Mandarin-speaking CI patients for recognition. All
patients used their own clinical speech processors in the testing. RESULTS:
Significant improvements in speech intelligibility were observed with most noise
suppression methods. Further analysis indicated that NR algorithms could
effectively preserve the phonetic boundaries, which are critical for speech
perception, and also the fundamental frequency (F0) representation was moderately
improved by the NR methods. CONCLUSIONS: The present study demonstrated that
although most single-channel NR algorithms could effectively improve speech
recognition in noise for Mandarin-speaking CI listeners, these algorithms perform
differently in various environmental noises, and it would be beneficial for the
CI sound processor to integrate NR methods tailored to individual types of noises
for the best cost and benefit tradeoff. In addition, the intelligibility
improvement may be attributed to the restoration of acoustic landmark information
and the improved representation of temporal F0 cues.
PMID- 25127320
TI - Hearing function in patients living with HIV/AIDS.
AB - OBJECTIVES: During the earlier years of the HIV/AIDS epidemic, initial reports
described sensorineural hearing loss in up to 49% of individuals with HIV/AIDS.
During those years, patients commonly progressed to advanced stages of HIV
disease and frequently had neurological complications. However, the abnormalities
on pure-tone audiometry and brainstem-evoked responses outlined in small studies
were not always consistently correlated with advanced stages of HIV/AIDS.
Moreover, these studies could not exclude the confounding effect of concurrent
opportunistic infections and syphilis. Additional reports also have indicated
that some antiretroviral medications may be ototoxic; thus, it has been difficult
to make conclusions regarding the cause of changes in hearing function in HIV
infected patients. More recently, accelerated aging has been suggested as a
potential explanation for the disproportionate increase in complications of aging
described in many HIV-infected patients; hence, accelerated aging-associated
hearing loss may also be playing a role in these patients. DESIGN: We conducted a
large cross-sectional analysis of hearing function in over 300 patients with HIV
1 infection and in 137 HIV-uninfected controls. HIV-infected participants and HIV
uninfected controls underwent a 2-hr battery of hearing tests including the
Hearing Handicap Inventory, standard audiometric pure-tone air and bone
conduction testing, tympanometric testing, and speech reception and
discrimination testing. RESULTS: Three-way analysis of variance (ANOVA) and
logistic regression analysis of 278 eligible HIV-infected subjects stratified by
disease stage in early HIV disease (n = 127) and late HIV disease (n = 148) and
120 eligible HIV-uninfected controls revealed no statistically significant
differences among the three study groups in either overall 4-frequency pure-tone
average (4-PTA) or hearing loss prevalence in either ear. Three-way ANOVA showed
significant differences in word recognition scores in the right ear among groups,
a significant group effect on tympanogram static admittance in both ears and a
significant group effect on tympanic gradient in the right ear. There was
significantly larger admittance and gradient in controls as compared to the HIV
infected group at late stage of disease. Hearing loss in the HIV-infected groups
was associated with increased age and was similar to that described in the
literature for the general population. Three-way ANOVA analysis also indicated
significantly greater pure-tone thresholds (worse hearing) at low frequencies in
HIV patients in the late stage of disease compared with HIV-uninfected controls.
This difference was also found by semi-parametric mixed effects models.
CONCLUSIONS: Despite reports of "premature" or "accelerated" aging in HIV
infected subjects, we found no evidence of hearing loss occurring at an earlier
age in HIV-infected patients compared to HIV-uninfected controls. Similar to what
is described in the general population, the probability of hearing loss increased
with age in the HIV-infected subjects and was more common in patients over 60
years of age. Interestingly, HIV-infected subjects had worse hearing at lower
frequencies and have significant differences in tympanometry compared to HIV
uninfected controls; these findings deserve further study.
PMID- 25127322
TI - Interaural level differences and sound source localization for bilateral cochlear
implant patients.
AB - OBJECTIVES: The aims of this study were (i) to determine the magnitude of the
interaural level differences (ILDs) that remain after cochlear implant (CI)
signal processing and (ii) to relate the ILDs to the pattern of errors for sound
source localization on the horizontal plane. DESIGN: The listeners were 16
bilateral CI patients fitted with MED-EL CIs and 34 normal-hearing listeners. The
stimuli were wideband, high-pass, and low-pass noise signals. ILDs were
calculated by passing signals, filtered by head-related transfer functions
(HRTFs) to a Matlab simulation of MED-EL signal processing. RESULTS: For the
wideband signal and high-pass signals, maximum ILDs of 15 to 17 dB in the input
signal were reduced to 3 to 4 dB after CI signal processing. For the low-pass
signal, ILDs were reduced to 1 to 2 dB. For wideband and high-pass signals, the
largest ILDs for +/-15 degree speaker locations were between 0.4 and 0.7 dB; for
the +/-30 degree speaker locations between 0.9 and 1.3 dB; for the 45 degree
speaker locations between 2.4 and 2.9 dB; for the +/-60 degree speaker locations,
between 3.2 and 4.1 dB; and for the +/-75 degree speaker locations between 2.7
and 3.4 dB. All of the CI patients in all the stimulus conditions showed poorer
localization than the normal-hearing listeners. Localization accuracy for the CI
patients was best for the wideband and high-pass signals and was poorest for the
low-pass signal. CONCLUSIONS: Localization accuracy was related to the magnitude
of the ILD cues available to the normal-hearing listeners and CI patients. The
pattern of localization errors for the CI patients was related to the magnitude
of the ILD differences among loudspeaker locations. The error patterns for the
wideband and high-pass signals, suggest that, for the conditions of this
experiment, patients, on an average, sorted signals on the horizontal plane into
four sectors-on each side of the midline, one sector including 0, 15, and
possibly 30 degree speaker locations, and a sector from 45 degree speaker
locations to 75 degree speaker locations. The resolution within a sector was
relatively poor.
PMID- 25127323
TI - Automated screening for high-frequency hearing loss.
AB - OBJECTIVE: Hearing loss at high frequencies produces perceptual difficulties and
is often an early sign of a more general hearing loss. This study reports the
development and validation of two new speech-based hearing screening tests in
English that focus on detecting hearing loss at frequencies above 2000 Hz.
DESIGN: The Internet-delivered, speech-in noise tests used closed target-word
sets of digit triplets or consonant-vowel-consonant (CVC) words presented against
a speech-shaped noise masker. The digit triplet test uses the digits 0 to 9
(excluding the disyllabic 7), grouped in quasi-random triplets. The CVC test uses
simple words (e.g., "cat") selected for the high-frequency spectral content of
the consonants. During testing, triplets or CVC words were identified in an
adaptive procedure to obtain the speech reception threshold (SRT) in noise. For
these new, high-frequency (HF) tests, the noise was low-pass filtered to produce
greater masking of the low-frequency speech components, increasing the
sensitivity of the test for HF hearing loss. Individual test tokens (digits,
CVCs) were first homogenized using a group of 10 normal-hearing (NH) listeners by
equalizing intelligibility across tokens at several speech-in-noise levels. Both
tests were then validated and standardized using groups of 24 NH listeners and 50
listeners with hearing impairment. Performance on the new high frequency digit
triplet (HF-triplet) and CVC (HF-CVC) tests was compared with audiometric hearing
loss, and with that on the unfiltered, broadband digit triplet test (BB-triplet)
test, and the ASL (Adaptive Sentence Lists) speech-in-noise test. RESULTS: The HF
triplet and HF-CVC test results (SRT) both correlated positively and highly with
high-frequency audiometric hearing loss and with the ASL test. SRT for both tests
as a function of high-frequency hearing loss increased at nearly three times the
rate as that of the BB-triplet test. The intraindividual variability (SD) on the
tests was about 2.1 (HF-triplet) and 1.7 (HF-CVC) times less than that for the BB
triplet test. The effect on the HF-triplet test of varying presentation method
(professional or cheap headphones and loudspeakers) was small for the NH group
and somewhat larger, but nonsignificant for the hearing-impaired group. Test
repetition produced a moderate, significant learning effect for the first and
second retests, but was small and nonsignificant for further retesting. The
learning effect was about two times larger for the HF-CVC test than for the HF
triplet test. The sensitivity of both new tests for high-frequency hearing loss
was similar, with an 87% true-positive and 7% false-positive ratio for detecting
an average high-frequency hearing loss of 20 dB or more. CONCLUSIONS: The new HF
triplet and HF-CVC tests provide a sensitive and accurate method for detecting
high-frequency hearing loss. The tests may signal developing hearing impairment
at an early stage. The HF-triplet is preferred over the HF-CVC test because of
its smaller learning effect, smaller error rate, greater simplicity, and lower
cultural dependency.
PMID- 25127325
TI - FS4, FS4-p, and FSP: a 4-month crossover study of 3 fine structure sound-coding
strategies.
AB - OBJECTIVES: The aim of the present study was to compare two novel fine structure
strategies "FS4" and "FS4-p" with the established fine structure processing (FSP)
strategy. FS4 provides fine structure information on the apical four-electrode
channels. With FS4-p, these electrodes may be stimulated in a parallel manner.
The authors evaluated speech perception, sound quality, and subjective
preference. DESIGN: A longitudinal crossover study was done on postlingually
deafened adults (N = 33) who were using FSP as their default strategy. Each
participant was fitted with FS4, FS4-p, and FSP, for 4 months in a randomized and
blinded order. After each run, an Adaptive Sentence test in noise (Oldenburger
Sentence Test [OLSA]) and a Monosyllable test in quiet (Freiburger Monosyllables)
were performed, and subjective sound quality was determined with a Visual
Analogue Scale. At the end of the study the preferred strategy was noted.
RESULTS: Scores of the OLSA did not reveal any significant differences among the
three strategies, but the Freiburger test showed a statistically significant
effect (p = 0.03) with slightly worse scores for FS4 (49.7%) compared with FSP
(54.3%). Performance of FS4-p (51.8%) was comparable with the other strategies.
Both audiometric tests depicted a high variability among subjects. The number of
best-performing strategies for each participant individually was as follows: (a)
for the OLSA: FSP, N = 10.5; FS4, N = 10.5; and FS4-p, N = 12; and (b) for the
Freiburger test: FSP, N = 14; FS4, N = 9; and FS4-p, N = 10. A moderate agreement
was found in the best-performing strategies of the Speech tests within the
participants. For sound quality, speech in quiet, classical, and pop music were
assessed. No significant effects of strategy were found for speech in quiet and
classical music, but auditory impression of pop music was rated as more natural
in FSP compared with FS4 (p = 0.04). It is interesting that at the end of the
study, a majority of the participants favored the new coding strategies over
their previous default FSP (FSP, N = 13; FS4, N = 13; FS4-p, N = 7). CONCLUSIONS:
In summary, FS4 and FS4-p offer new and further options in audio processor
fitting, with similar levels of speech understanding in noise as FSP. This is an
interesting result, given that the strategies' presentation of temporal fine
structure differs from FSP. At the end of the study, 20 of 33 subjects chose
either FS4 or FS4-p over their previous default strategy FSP.
PMID- 25127324
TI - Evaluation of ototoxicity in patients treated with hyperthermic intraperitoneal
chemotherapy (HIPEC) with cisplatin and sodium thiosulfate.
AB - OBJECTIVES: Ototoxic hearing loss associated with intravenous or intra-arterial
administration of cisplatin is well documented. However, there is limited data
regarding the ototoxic effect of cisplatin when perfused into the abdominal
cavity using hyperthermic intraperitoneal chemotherapy (HIPEC). The purpose of
this study is to assess and describe ototoxicity in patients treated with HIPEC
with cisplatin and sodium thiosulfate for peritoneal surface malignancies.
DESIGN: We performed a retrospective chart review (2007-2012) of patients treated
for advanced peritoneal malignancies at a tertiary care center using HIPEC with
cisplatin and sodium thiosulfate infusion. Thirteen patients (12 males, 1 female)
met study criteria. Audiometric thresholds were compared before and after
treatment. A 20 dB loss at any single frequency, 10 dB decrease at any two
adjacent frequencies, or loss of response at three consecutive test frequencies
defined a significant ototoxic change (). RESULTS: Despite minimal hearing change
in six patients, none of the 13 patients in our study exhibited a significant
ototoxic change in hearing sensitivity post HIPEC with cisplatin at any test
interval in any test frequency. CONCLUSIONS: Our findings represent the first
objective assessment of ototoxic effect after HIPEC with cisplatin and sodium
thiosulfate infusion. Our results suggest that peritoneal perfusion of cisplatin
with intravenous perfusion of sodium thiosulfate is not associated with ototoxic
changes in hearing sensitivity. Further investigation of the administration and
systemic mechanism of absorption of sodium thiosulfate as a potential protection
against cisplatin ototoxicity is needed to confirm these findings.
PMID- 25127326
TI - Is "no response" on diagnostic auditory brainstem response testing an indication
for cochlear implantation in children?
AB - OBJECTIVES: To compare the results of a "no response" (NR) result on auditory
brainstem response (ABR) testing with those of behavioral pure-tone audiometry
and ultimate clinical tracking to cochlear implantation (CI). DESIGN:
Retrospective review of pediatric patients who underwent multifrequency ABR
testing in a 5 year span. Total of 1143 pediatric patients underwent ABR testing
during the study period and 105 (9.2%) were identified with bilateral NR based on
absent responses to both click and tone burst stimuli. For the children with NR,
various clinical parameters were evaluated as these children progressed through
the CI evaluation process. Children were grouped based on whether they underwent
ABRs for diagnostic or for confirmatory purposes. RESULTS: Of the 105 children
who met inclusion criteria, 94 had sufficient follow-up to be included in this
analysis. Ninety-one (96.8%) of 94 children with bilateral NR ABRs were
ultimately recommended for and received a CI. Three (3.2%) children were not
recommended for implantation based on the presence of multiple comorbidities
rather than auditory factors. None of the children (0%) had enough usable
residual hearing to preclude CI. For those who had diagnostic ABRs, the average
time at ABR testing was 5.4 months (SD 6.2, range 1-36) and the average time from
ABR to CI was 10.78 months (SD 5.0, range 3-38). CONCLUSIONS: CI should
tentatively be recommended for children with a bilateral NR result with
multifrequency ABR, assuming confirmatory results with behavioral audiometric
testing. Amplification trials, counseling, and auditory-based intervention
therapy should commence but not delay surgical intervention, as it does not
appear to change the eventual clinical course. Children not appropriate for this
"fast-tracking" to implantation might include those with significant
comorbidities, auditory neuropathy spectrum disorder, and unreliable or poorly
correlated results on behavioral audiometric testing.
PMID- 25127327
TI - Intelligibility of emotional speech in younger and older adults.
AB - OBJECTIVES: Little is known about the influence of vocal emotions on speech
understanding. Word recognition accuracy for stimuli spoken to portray seven
emotions (anger, disgust, fear, sadness, neutral, happiness, and pleasant
surprise) was tested in younger and older listeners. Emotions were presented in
either mixed (heterogeneous emotions mixed in a list) or blocked (homogeneous
emotion blocked in a list) conditions. Three main hypotheses were tested. First,
vocal emotion affects word recognition accuracy; specifically, portrayals of fear
enhance word recognition accuracy because listeners orient to threatening
information and/or distinctive acoustical cues such as high pitch mean and
variation. Second, older listeners recognize words less accurately than younger
listeners, but the effects of different emotions on intelligibility are similar
across age groups. Third, blocking emotions in list results in better word
recognition accuracy, especially for older listeners, and reduces the effect of
emotion on intelligibility because as listeners develop expectations about vocal
emotion, the allocation of processing resources can shift from emotional to
lexical processing. DESIGN: Emotion was the within-subjects variable: all
participants heard speech stimuli consisting of a carrier phrase followed by a
target word spoken by either a younger or an older talker, with an equal number
of stimuli portraying each of seven vocal emotions. The speech was presented in
multi-talker babble at signal to noise ratios adjusted for each talker and each
listener age group. Listener age (younger, older), condition (mixed, blocked),
and talker (younger, older) were the main between-subjects variables. Fifty-six
students (Mage= 18.3 years) were recruited from an undergraduate psychology
course; 56 older adults (Mage= 72.3 years) were recruited from a volunteer pool.
All participants had clinically normal pure-tone audiometric thresholds at
frequencies <=3000 Hz. RESULTS: There were significant main effects of emotion,
listener age group, and condition on the accuracy of word recognition in noise.
Stimuli spoken in a fearful voice were the most intelligible, while those spoken
in a sad voice were the least intelligible. Overall, word recognition accuracy
was poorer for older than younger adults, but there was no main effect of talker,
and the pattern of the effects of different emotions on intelligibility did not
differ significantly across age groups. Acoustical analyses helped elucidate the
effect of emotion and some intertalker differences. Finally, all participants
performed better when emotions were blocked. For both groups, performance
improved over repeated presentations of each emotion in both blocked and mixed
conditions. CONCLUSIONS: These results are the first to demonstrate a
relationship between vocal emotion and word recognition accuracy in noise for
younger and older listeners. In particular, the enhancement of intelligibility by
emotion is greatest for words spoken to portray fear and presented
heterogeneously with other emotions. Fear may have a specialized role in
orienting attention to words heard in noise. This finding may be an auditory
counterpart to the enhanced detection of threat information in visual displays.
The effect of vocal emotion on word recognition accuracy is preserved in older
listeners with good audiograms and both age groups benefit from blocking and the
repetition of emotions.
PMID- 25127328
TI - Long-term hearing deficits after childhood middle ear disease.
AB - OBJECTIVES: To investigate the long-term impact of childhood otitis media on
listening ability in school-aged children. DESIGN: Speech perception in
background noise was measured in two groups of 35 children, aged 6 to 12 years,
with normal middle ear function and sound detection at assessment. The first
consisted of children who had previously suffered middle ear disease; the second
those with no history of middle ear disease. RESULTS: Binaural speech perception
ability was significantly poorer in the children with prior middle ear disease.
Furthermore, spatial listening (the ability to selectively attend to a sound
signal from one location) was also significantly impaired. Significant
correlations were demonstrated between both the age of onset and the duration of
childhood otitis media and speech perception ability (onset: r = -0.58, p <
0.001; duration: r = -0.63, p < 0.001). CONCLUSIONS: These results demonstrate
the risk of long-term functional hearing deficit for children with middle ear
disease history in childhood. They also indicate that this risk is increased with
earlier onset and longer duration. The findings highlight the need for early
intervention and an awareness of the potential for reduced functional listening
ability even after sound detection has returned to normal.
PMID- 25127330
TI - The SOX transcription factors as key players in pluripotent stem cells.
AB - Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs), and induced
PSCs (iPSCs) are able to self-renew and differentiate into a multitude of
specialized cellular lineages. In these cells, the pluripotential identity is
maintained by a group of transcription factors (TFs). Among these factors, SOX
TFs play an essential role, not only in regulating pluripotency but also in
mediating self-renewal and differentiation. Some SOX TFs are highly expressed in
undifferentiated PSCs, while others are upregulated upon differentiation to
promote specific lineage differentiation. Further roles of SOX factors in
pluripotency are highlighted through their critical involvement in iPSCs
generation. To perform these multiple functions and activities, SOX TFs are
strongly associated with a complex regulatory network(s) that involves the
binding of SOX factors to variant trans-acting partners to activate or suppress
specific genes. Although, SOX2 has attracted special attention as a critical
factor in maintaining PSCs characteristics and as an integral component that is
required to reprogram somatic cells into pluripotency, new reports widely
appreciated that other SOX TFs, such as SOX1, SOX3, or reengineered SOX7 and
SOX17, can compensate for the absence of SOX2 and thus play a fundamental role
during the reprogramming process and maintaining pluripotency. These findings
indicate that the recent progress has greatly expanded our knowledge about the
role of SOX factors in PSCs. Thus, in this review we summarize what is currently
known about the roles of SOX factors in PSCs and their role in somatic cell
reprogramming. Also, we intend to provide an update on their relationship with
other factors in regulating the characteristics and early differentiation of
PSCs.
PMID- 25127329
TI - Studying progression from glucose intolerance to type 2 diabetes in obese
children.
AB - AIM: Identification of metabolic and genetic factors capable to mediate
progression from normal glucose tolerance (NGT) through impaired glucose
tolerance (IGT) to type 2 diabetes (T2D) in childhood obesity. PATIENTS AND
METHODS: Three groups of obese children with NGT (n=54), IGT (n=35), and T2D
(n=62) were evaluated. A control group of non-obese normal children (n=210) was
also studied. In obese patients, an oral glucose tolerance test (OGTT) was
performed. Insulin resistance (IR) was assessed using HOMA-IR index. Insulin
sensitivity (IS) was assessed according to the Matsuda formula. Genomic DNA from
obese and control children was genotyped for genetic variants of PPARG, ADIPOQ,
ADIPOR1, FTO, TCF7L2, and KCNJ11 using a real-time PCR strategy. The unpaired
Student's t-test and Kruskal-Wallis one-way test were used to compare
quantitative data in two and more groups. To assess the extent to which the
various genetic variants were associated with pathology, ORs (odds ratios) and
95% CI (confidence interval) were estimated. RESULTS: In T2D children, HOMA-IR
value (7.5+/-3.1) was significantly (P<0.001) higher than that in IGT (4.21+/
2.25) and NGT (4.1+/-2.4) subjects. The Matsuda IS index was significantly
increased in normoglycemic patients compared to IGT individuals (2.8+/-1.75 vs.
2.33+/-1.2, P<0.05). The Pro12Ala polymorphism of PPARG was significantly
associated with obesity (OR=1.74, 95% CI=1.19-2.55, P=0.004) and T2D in obesity
(OR=2.01, 95% CI=1.24-3.26, P=0.004). CONCLUSION: IR is a major risk factor that
mediates progression from NGT to clinical T2D in Russian obese children. This
progression may be genetically influenced by the Pro12Ala variant of PPARG.
PMID- 25127331
TI - Heteroaggregation of titanium dioxide nanoparticles with model natural colloids
under environmentally relevant conditions.
AB - The heteroaggregation of engineered nanoparticles (ENPs) with natural colloids
(NCs), which are ubiquitous in natural surface waters, is a crucial process
affecting the environmental transport and fate of ENPs. Attachment efficiencies
for heteroaggregation, alpha hetero, are required as input parameters in
environmental fate models to predict ENP concentrations and contribute to ENP
risk assessment. Here, we present a novel method for determining alpha hetero
values by using a combination of laser diffraction measurements and aggregation
modeling based on the Smoluchowski equation. Titanium dioxide nanoparticles (TiO2
NPs, 15 nm) were used to demonstrate this new approach together with larger
silicon dioxide particles (SiO2, 0.5 MUm) representing NCs. Heteroaggregation
experiments were performed at different environmentally relevant solution
conditions. At pH 5 the TiO2 NPs and the SiO2 particles are of opposite charge,
resulting in alpha hetero values close to 1. At pH 8, where all particles are
negatively charged, alpha hetero was strongly affected by the solution
conditions, with alpha hetero ranging from <0.001 at low ionic strength to 1 at
conditions with high NaCl or CaCl2 concentrations. The presence of humic acid
stabilized the system against heteroaggregation.
PMID- 25127332
TI - Characteristics of acute heart failure hospitalizations in a general medical ward
in Southwestern Uganda.
PMID- 25127333
TI - Morphologic characteristics of eroded coronary plaques: a combined angiographic,
optical coherence tomography, and intravascular ultrasound study.
PMID- 25127334
TI - Seven french radial artery access for PCI: a prospective single-center
experience.
PMID- 25127335
TI - Precordial chest pain in patients with chronic Chagas disease.
AB - Precordial chest pain affects about 15% to 33% of patients with chronic Chagas
disease. In the absence of megaesophagus, it should be ascribed to chronic Chagas
heart disease. Precordial chest pain is atypical because it can usually neither
be associated to physical exercise nor be alleviated by nitroglycerin. However,
in certain circumstances, precordial chest pain can masquerade as acute coronary
syndrome. Although obstructive coronary artery disease can occasionally be found,
microvascular angina seems to be the mechanism behind such phenomenon. Precordial
chest pain not always has a benign clinical course; sometimes, it can herald a
dismal prognosis. On the basis of cases previously reported, it seems that
nitrates, betablockers and/or calcium channel blockers can be of value in the
treatment of this condition.
PMID- 25127336
TI - Acute eosinophilic myocarditis.
PMID- 25127337
TI - Early changes of myocardial deformation properties in patients with dystrophia
myotonica type 1: a three-dimensional Speckle Tracking echocardiographic study.
PMID- 25127338
TI - Real-time photoacoustic imaging system for burn diagnosis.
AB - We have developed a real-time (8 to 30 fps) photoacoustic (PA) imaging system
with a linear-array transducer for burn depth assessment. In this system, PA
signals originating from blood in the noninjured tissue layer located under the
injured tissue layer are detected and imaged. A compact home-made high-repetition
rate (500 Hz) 532-nm fiber laser was incorporated as a light source. We used an
alternating arrangement for the fibers and sensor elements in the probe, which
improved the signal-to-noise ratio, reducing the required laser energy power for
PA excitation. This arrangement also enabled a hand-held light-weight probe
design. A phantom study showed that thin light absorbers embedded in the tissue
mimicking scattering medium at depths >3 mm can be imaged with high contrast. The
maximum error for depth measurement was 140 MUm. Diagnostic experiments were
performed for rat burn models, including superficial dermal burn, deep dermal
burn, and deep burn models. Injury depths (zones of stasis) indicated by PA
imaging were compared with those estimated by histological analysis, showing
discrepancies 200 MUm. The system was also used to monitor the healing process of
a deep dermal burn. The results demonstrate the potential usefulness of the
present system for clinical burn diagnosis.
PMID- 25127339
TI - Copper-catalyzed domino reactions for the synthesis of cyclic compounds.
AB - Copper-catalyzed domino reactions are one of the most useful strategies for the
construction of various cyclic compounds. In this Synopsis, we mainly focus on
the latest advances in copper-catalyzed cross-coupling or addition-initiated
domino reactions in the synthesis of cyclic compounds, including double
alkenylation of N- or S-nucleophiles, alkenylation or alkynlation followed by
cyclization of amides or amines, addition and cyclization of heteroallenes
affording heterocycles, and coupling and cyclization of 1,3-dicarbonyl compounds
toward heterocycles.
PMID- 25127340
TI - Colloids with continuously tunable surface charge.
AB - In this paper, we present a robust way to tune the surface potential of
polystyrene colloids without changing the pH, ionic strength, etc. The colloids
are composed of a cross-linked polystyrene core and a cross-linked vinylbenzyl
chloride layer. Besides the chlorine groups, the particle surface contains
sulfate/sulfonate groups (arising from the polymerization initiators) that
provide a negative surface potential. Performing a Menschutkin reaction on the
surface chlorine groups with tertiary amines allows us to introduce quaternary,
positively charged amines. The overall charge on the particles is then determined
by the ratio between the sulfate/sulfonate moieties and the quaternary amines.
Using this process, we were able to invert the charge in a continuous manner
without losing colloidal stability upon passing the isoelectric point. The
straightforward reaction mechanism together with the fact that the reaction could
be quenched rapidly resulted in a colloidal system in which the zeta potential
can be tuned between -80 and 45 mV. As proof of principle, the positively charged
particles were used in heterocoagulation experiments with nanometer- and
micrometer-sized negatively charged silica particles to create geometrically well
defined colloidal (nano) clusters.
PMID- 25127341
TI - Social self-perception among pediatric brain tumor survivors compared with peers.
AB - OBJECTIVE: To assess self-perceptions of social behavior among children treated
for a brain tumor and comparison children. To investigate group differences in
the accuracy of children's self-perceptions as measured by discrepancies between
self and peer reports of social behavior and to understand if these phenomena
differ by gender. METHOD: Self and peer reports of social behavior were obtained
in the classrooms of 116 children who were treated for an intracranial tumor.
Social behaviors were assessed using the Revised Class Play, which generates
indices for 5 behavioral subscales: Leadership-popularity, Prosocial, Aggressive
disruptive, Sensitive-isolated, and Victimization. A child matched for gender,
race, and age was selected from each survivor's classroom to serve as a
comparison. Abbreviated IQ scores were obtained in participants' homes. RESULTS:
Relative to comparison children, those who had undergone treatment for a brain
tumor overestimated their level of Leadership-popularity and underestimated
levels of Sensitive-isolated behaviors and Victimization by peers. Female
survivors were more likely than male survivors to underestimate Sensitive
isolated behaviors and Victimization. CONCLUSION: Following treatment for a brain
tumor, children (particularly girls) may be more likely than healthy children to
underestimate peer relationship difficulties. These discrepancies should be
considered when obtaining self-report from survivors and developing interventions
to improve social functioning.
PMID- 25127342
TI - "More than meets the eye": when the neonatal course may impact several years out.
AB - CASE: Nadia is a 7-year-old girl who you have followed since her discharge from
the Neonatal Intensive Care Unit (NICU). Her parents are here today for an urgent
visit with behavioral concerns, such as inattention, hyperactivity, and
aggression.Nadia is a former 40-weeker born through vacuum-assisted vaginal
delivery at 9 pounds 7 ounces. Her delivery was complicated with shoulder
dystocia, which resulted in resuscitation. Her Apgar scores were 1, 3, and 4 at
1, 5, and 10 minutes, respectively. After intubation and stabilization on
mechanical ventilation, Nadia was transferred to the NICU. Her neonatal course
included systemic hypothermia using "cool cap" for hypoxic-ischemic
encephalopathy (HIE) for a duration of 72 hours. She was extubated on day of life
3. She had an occupational therapy consultation for poor suck/feeding, and it
quickly improved. She was discharged on day of life 14. On discharge, Nadia was
referred to early intervention (EI) and the NICU follow-up clinic. Nadia was
followed by EI until 12 months of age and in the NICU follow-up clinic until 18
months of age, as there were no concerns meeting her developmental milestones or
her neuromotor development.At this urgent visit, Nadia's parents report that she
attended a family child care from 1.5 to 3 years of age, Head Start from 3 to 5
years of age and the local public school from 5 years to present. Since starting
child care, Nadia's teachers have reported that she requires a lot of redirection
and refocusing, fidgets a lot in class, and can be aggressive toward her peers
when unprovoked. Since her parents had not seen these behaviors at home, they
thought it was a phase that she would grow out of. However, as they began to work
with her to complete school assignments, they noticed that it was very difficult
for Nadia to sit still and focus on work. They also struggled in the mornings to
get her ready and off to school.The parents bring in Conners scales completed by
themselves and her lead teacher, and with these and our clinical observations, we
diagnose her with attention-deficit/hyperactivity disorder (ADHD), combined type.
We discuss risk factors and ADHD management with her parents. During our
discussion, Nadia's father, who has done some reading on ADHD, remembers reading
an article about HIE and NICU stay being risk factors for ADHD. He wonders if
this affects the choice of management of her ADHD symptoms. How would you address
his query?
PMID- 25127344
TI - [Discussion welcome].
PMID- 25127343
TI - Perfluorochemicals and human semen quality: the LIFE study.
AB - BACKGROUND: The relation between persistent environmental chemicals and semen
quality is evolving, although limited data exist for men recruited from general
populations. OBJECTIVES: We examined the relation between perfluorinated
chemicals (PFCs) and semen quality among 501 male partners of couples planning
pregnancy. METHODS: Using population-based sampling strategies, we recruited 501
couples discontinuing contraception from two U.S. geographic regions from 2005
through 2009. Baseline interviews and anthropometric assessments were conducted,
followed by blood collection for the quantification of seven serum PFCs
(perfluorosulfonates, perfluorocarboxylates, and perfluorosulfonamides) using
tandem mass spectrometry. Men collected a baseline semen sample and another
approximately 1 month later. Semen samples were shipped with freezer packs, and
analyses were performed on the day after collection. We used linear regression to
estimate the difference in each semen parameter associated with a one unit
increase in the natural log-transformed PFC concentration after adjusting for
confounders and modeling repeated semen samples. Sensitivity analyses included
optimal Box-Cox transformation of semen quality end points. RESULTS: Six PFCs [2
(N-methyl-perfluorooctane sulfonamido) acetate (Me-PFOSA-AcOH),
perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), perfluorooctane
sulfonamide (PFOSA), perfluorooctane sulfonate (PFOS), and perfluorooctanoic acid
(PFOA)] were associated with 17 semen quality end points before Box-Cox
transformation. PFOSA was associated with smaller sperm head area and perimeter,
a lower percentage of DNA stainability, and a higher percentage of bicephalic and
immature sperm. PFDeA, PFNA, PFOA, and PFOS were associated with a lower
percentage of sperm with coiled tails. CONCLUSIONS: Select PFCs were associated
with certain semen end points, with the most significant associations observed
for PFOSA but with results in varying directions.
PMID- 25127345
TI - [Substance abuse and pregnancy from an obstetric point of view].
AB - INTRODUCTION: In Germany we find about 2 000 newborns per year with a mother
misusing drugs. It is to be feared that there is a substantial amount of
underreported substance abuse in pregnant women. To care for these pregnancies
from an obstetric point of view as well as from an addiction treatment point of
view is a challenge for all health-care professionals, due to multiple drugs
being used and the special psychosocial and health issues these mothers and
babies -present. METHOD: A selective search was undertaken in Pubmed, retrieving
reviews and original articles from 2001-2013, with consideration of statements,
recommendations and guidelines from national and international associations and
committees on the topic. This review is intended to assist gynaecologists,
obstetricians and paediatricians during the complex peripartum care for the drug
abusing pregnant patient. RESULTS: When offering obstetric care for these
pregnancies, several issues have to be taken into account: the special
psychological situation of the pregnant drug user, with frequent occurrence of
psychiatric comorbidities like depression and anxiety disorders, as well as
gynaecological complications like premature labour, intrauterine growth
restriction and maternal infectious diseases. The pharmacological complexity of
the substances abused and the possible side-effects on the foetus have to be
explained to the mother. Maintenance medication for foetomaternal risk reduction
and maternal stabilisation remains the state-of-the-art treatment. Furthermore,
it is important to explain the neonatal abstinence syndrome to the mother as well
as the result of breast-feeding in the presence of smoking and/or infectious
diseases. DISCUSSION: Professionalism and empathy are needed from gynaecologists
in order to achieve risk reduction for mother and child in substance-using
pregnancies. However, in spite of close cooperation of all health-care
professionals and avoidance of stigma, it will be difficult to offer good
obstetric care to the high-risk patients with poly-drug abuse.
PMID- 25127346
TI - [Preconceptional use of folic acid in the region of the Kantonsspital
Munsterlingen/Thurgau: has it changed over the past 10 years?].
AB - BACKGROUND: Numerous studies have shown that the preconceptional use of folic
acid prevents neural tube defects. We created a study to find out whether the
preconceptional use of folic acid has improved in the past 10 years, in the area
of Munsterlingen, Switzerland. MATERIAL AND METHODS: We interviewed 2 groups of
patients who delivered at our Institution, namely between 2000 and 2002 (period
A) involving 287 women and from 2009 to 2010 (period B) involving 305 pregnant
women. We asked them whether they used folic acid by means of a standardised
questionnaire. RESULTS: In period B significantly more women have taken folic
acid preconceptionally (period A: 27.5% vs. period B: 40.7%; p=0.001). A
significant increase in folic acid intake was seen in the German speaking group
from period A to B (30.3% vs. 52.7%; p=0.0005), while this was not the case in
the non-German speaking group (21.4% in both periods). More multiparae women were
taking folic acid compared to nulliparae. A significant increase from period A to
B was noted only in the German speaking group. Unexpectedly, in nulliparae non
German speaking women, folic acid supplementation decreased from 14% to 6.1%.
DISCUSSION: We have found a significant increase in preconceptional folic acid
supplementation from 2001 to 2010. The percentage of women taking folic acid is
disappointingly low in all groups, particularly in nulliparae women of non-German
ethnicity.
PMID- 25127347
TI - [Infant mortality in Germany (2008-2012)--lower in the former German Democratic
Republic?].
AB - BACKGROUND: German infant mortality is ranked near the median of European
countries. In Germany infant mortality is significantly higher in the German
Federal Republic compared with the former German Democratic Republic. This is
often used as reason for a call for structural requirements and minimum caseload
for the care for very low birth weight infants. METHOD: Neonatal and infant
mortality were calculated for the 16 German federal states with data from the
German statistical federal office for the years 2008-2012. RESULTS: Considerable
variations were found for the neonatal (1.34-3.610/00, total Germany 2.310/00)
and the infant (2.38-5.200/00, 3.470/00) mortality. The rate of stillborn infants
was 3.560/00. A lower neonatal mortality in the former German Democratic Republic
(1.620/00 vs. 2.440/00, p<0.0001, Chi-squared test) could not be confirmed for
preterm infants with birth weight less than 1 500 g. In the former German
Democratic Republic stillbirth was significantly more frequent in preterm infants
with birth weight 500-999 g (p<0.0001). Combined stillbirth and neonatal
mortality showed no difference between the German Federal Republic and former
German Democratic Republic (5.450/00 and 5.290/00, respectively, n.s.; infants
less than 500 g birth weight were excluded). The average number of preterm
infants per perinatal centre and federal state had no influence on state specific
neonatal mortality. CONCLUSION: If stillborn infants were accounted for no
difference was found between the German Federal Republic and the former German
Democratic Republic regarding mortality. Comparing infant mortality of different
countries has to account for stillborn infants. Considerable variation of
neonatal mortality is persisting throughout Germany despite structural
requirements and introduction of a minimum caseload since 2005. A lower infant
mortality in the former German Democratic Republic and implications drawn from
are not supported by the presented nationwide data from the German statistical
federal office.
PMID- 25127348
TI - [Infant mortality in Germany (2008-2012) - lower in the East?].
PMID- 25127349
TI - [Quality results in perinatal centers].
PMID- 25127350
TI - [Prevention of preterm birth by Shirodkar cerclage--clinical results of a
retrospective analysis].
AB - In spite of the continuous progress in prenatal care, 1 out of 10 babies is born
too early--tendency rising worldwide. As a consequence of the heterogeneous
aetiology of preterm birth, there is still no single and efficient interventional
therapy. Cerclage is one option for pregnancies with cervical insufficiency,
whereas the clinical benefit is discussed controversially. We analyzed in a
retrospective study with 120 patients the effect of a cerclage intervention
regarding pregnancy prolongation. Patients with cervical incompetence and
Shirodkar cerclage were compared to those undergoing conservative treatment. As
expected, gestational age at delivery was significantly lower after emergency
cerclage (31 weeks) compared to prophylactic (36 weeks) and therapeutic cerclage
(35 weeks). Prolongation differs significantly between the prophylactic (18
weeks), therapeutic (14 weeks) and emergency cerclage (10 weeks) groups.
Conservative management achieved 8 weeks prolongation. Of note, particularly
emergency cerclage in cases with advanced cervical incompetence resulted in a
substantially higher pregnancy prolongation (10 weeks) compared to no
intervention (one week). The efficiency of cerclage operations has to be assessed
in a differentiated manner based on the clinical situation and indication. The
clinical benefit depends strongly on proper patient selection.
PMID- 25127351
TI - Successful treatment of 1-34 parathyroid hormone (PTH) after failure of
bisphosphonate therapy in a complex case of pregnancy associated osteoporosis and
multiple fractures.
AB - INTRODUCTION: Pregnancy associated osteoporosis (PAO) was first reported almost
half a century ago. The most common symptom is acute lower back pain due to
vertebral fractures in the last trimester or immediately after birth. PATIENT: We
present a case involving a female patient born in 1971 (gravida II, para I) with
a history of PAO. In April 2000 at the age of 28 years, she delivered a son and
breastfed him for 4 months. A first magnetic resonance tomography (MRT) screening
in June 2000 showed osteoporotic fractures at lumbar vertebra 1-4. Therefore, the
patient received oral alendronate therapy. In May 2001, a second MRT exhibited
burst fracture of thoracic 8, end-plate fracture of thoracic 11, 12, lumbar 2-5
and compression fracture of lumbar 1. The oral therapy was switched to
ibandronate (3 mg) intravenously every 3 months. An X-ray in December 2002 showed
3 new additional end-plate fractures at thoracic 4, 6 and 7. Ibandronate was
discontinued in September 2004 and the patient received daily subcutaneous (s.
c.) injections of 1-34 PTH in September 2005. RESULTS: After starting 1-34 PTH
treatment for 18 months, a further increase in bone mineral density (BMD) was
achieved without any further fracture. CONCLUSION: We presented for the first
time a case of severe PAO with 11 spine fractures. We observed an unsatisfactory
effect of oral and i. v. bisphosphonates in combination with adequate calcium and
vitamin D supplementation. The treatment with 1-34 PTH showed an increase in BMD
with no further fractures.
PMID- 25127352
TI - Maternite Prize of the European Association of Perinatal Medicine. Laudatio for
Christian P. Speer, MD, FRCPE Professor of Pediatrics.
PMID- 25127354
TI - The browning of white adipose tissue: some burning issues.
AB - Igniting thermogenesis within white adipose tissue (i.e., promoting expression
and activity of the uncoupling protein UCP1) has attracted much interest.
Numerous "browning agents" have now been described (gene ablations, transgenes,
food components, drugs, environments, etc.). The implied action of browning
agents is that they increase UCP1 through this heat production, leading to
slimming. Here, we particularly point to the possibility that cause and effect
may on occasion be the reverse: browning agents may disrupt, for example, the
fur, leading to increased heat loss, increased thermogenic demand to counteract
this heat loss, and thus, through sympathetic nervous system activation, to
enhanced UCP1 expression in white (and brown) adipose tissues.
PMID- 25127353
TI - Fatty acid flippase activity of UCP2 is essential for its proton transport in
mitochondria.
AB - Modulation of cellular energy expenditure is fundamental to normal and
pathological cell growth and differentiation. Mitochondria stores energy as a
proton gradient across their inner membrane. Uncoupling proteins (UCPs) can
dissipate the gradient to produce heat or regulate metabolite fluxes. UCP
mediated proton currents require fatty acids (FAs) and are blocked by
nucleotides, but the molecular basis of these processes is unknown. We find, by
nuclear magnetic resonance and functional mutagenesis, that UCP2 can bind FAs
laterally through its peripheral site, and this intramembrane molecular
recognition is essential for UCP2-catalyzed FA flipping across the membrane,
which in turn is essential for proton translocation. The antagonist GDP binds
inside the UCP2 cavity and perturbs its conformation, which can displace FA from
the peripheral site as a mean of inhibiting proton currents. Our data provide a
biophysical perspective of the intricate interplay of UCPs, FA, and nucleotides
in determining proton fluxes in mitochondria.
PMID- 25127355
TI - Aggregation behavior of engineered nanoparticles and their impact on activated
sludge in wastewater treatment.
AB - The ever-increasing daily use of engineered nanoparticles will lead to heightened
levels of these materials in the environment. These nanomaterials will eventually
go into the wastewater treatment plant (WWTP), therefore, resulting into a
pressing need for information on their aggregation behavior and kinetics in the
wastewater aqueous matrix. In this work, we dispersed two different metal oxide
nanoparticles (ZnO and TiO2) into the influent of two different WWTPs. Through
the time-resolved dynamic light scattering analysis and transmission electron
microscopy, the metal oxide nanoparticles (NPs) were quite stably existed in the
wastewater matrix with aggregates of diameter 300-400 nm after 4.5h or more
suspension. We confirmed that the dissolved organic matters (DOMs) attributed to
the stability of nanoparticles. No propensity of NPs to aggregate were observed
in the presence of both monovalent and divalent electrolytes even at high
concentrations up to 0.15 M in NaCl or 0.025 M in CaCl2, indicating that the
destabilization of nanoparticles in the complicated wastewater matrix was not
achieved by the compression of electrical double layer, therefore, their
aggregation kinetics cannot be simply predicted by the classic Derjaguin-Landau
Verwey-Overbeek theory of colloidal stability. However, obvious aggregation of
nanoparticles in the Al2(SO4)3 solution system was observed with the likely
mechanism of bridging of the metal oxide nanoparticles and aggregates due to the
formation of hydrous alumina (Al(OH)3.H2O) in the Al2(SO4)3 solution. In the
wastewater matrix, we used the noninvasive measurement technology to detect the
O2 flux of activated sludge before and after treatment with 1, 10 and 100 mg L(
1) NPs. The results confirmed that both ZnO and TiO2 NPs showed an adverse impact
on the O2 uptake of activated sludge when the exposure time extended to 4.5 h.
PMID- 25127356
TI - The role of P450 metabolism in the estrogenic activity of bifenthrin in fish.
AB - Bifenthrin, a pyrethroid pesticide, is estrogenic in vivo in fishes. However,
bifenthrin is documented to be anti-estrogenic in vitro, in the ER-CALUX
(estrogen receptor) cell line. We investigated whether metabolite formation is
the reason for this incongruity. We exposed Menidia beryllina (inland
silversides) to 10ng/l bifenthrin, 10ng/l 4-hydroxy bifenthrin, and 10ng/l
bifenthrin with 25MUg/l piperonyl butoxide (PBO) - a P450 inhibitor. Metabolite
exposed juveniles had significantly higher estrogen-mediated protein levels
(choriogenin) than bifenthrin/PBO-exposed, while bifenthrin alone was
intermediate (not significantly different from either). This suggests that
metabolites are the main contributors to bifenthrin's in vivo estrogenicity.
PMID- 25127357
TI - Effect of bisphenol A on P-glycoprotein-mediated efflux and ultrastructure of the
sea urchin embryo.
AB - Usage of bisphenol A (BPA) in production of polycarbonate plastics has resulted
in global distribution of BPA in the environment. These high concentrations cause
numerous negative effects to the aquatic biota, among which the most known is the
induction of endocrine disruption. The focus of this research was to determine
the effects of two experimentally determined concentrations of BPA (100nM and
4MUM) on cellular detoxification mechanisms during the embryonic development (2
cell, pluteus) of the rocky sea urchin (Paracentrotus lividus), primarily the
potential involvement of multidrug efflux transport in the BPA intercellular
efflux. The results of transport assay, measurements of the intracellular BPA and
gene expression surveys, for the first time indicate the importance of P
glycoprotein (P-gp/ABCB1) in defense against BPA. Cytotoxic effects of BPA,
validated by the immunohistochemistry (IHC) and the transmission electron
microscopy (TEM), induced the aberrant karyokinesis, and consequently, the
impairment of embryo development through the first cell division and retardation.
PMID- 25127358
TI - The prevalence of abnormal genital findings, vulvovaginitis, enuresis and
encopresis in children who present with allegations of sexual abuse.
AB - OBJECTIVE: To assess the prevalence of vulvovaginitis, enuresis and encopresis in
children who were referred for allegations of sexual abuse. SUBJECTS: A
retrospective chart review of 1280 children presenting for non-acute examination
after allegations of sexual abuse during a 15-year time span. Interview
documentation, physical examination documentation, urinalysis, urine and vaginal
cultures were reviewed. RESULTS: Of the 1280 children, 73.3% were female and
26.7% male. The ages of the children ranged from 6 months to 18 years (median age
was 6 years). Interviews revealed that fondling contact was the most common
allegation, followed by oral, vaginal, and anal penetration. Interviews also
disclosed lower urinary tract symptoms, UTI, constipation, encopresis and
enuresis. Physical examination revealed no abnormal genital findings in 44.7% of
cases. Examinations of the vagina noted: erythema (18.1%); hymenal notching
(posterior 16.8%, anterior 4.4%); vuvlovaginitis (14.0%); laceration or
transection (0.6%); and bruising (0.4%). Examination of the anus noted: anal
fissure/tear (14.9%); loss of anal tone (10.6%); reflex anal dilatation (9.2%);
venous congestion (3.8%); and proctitis (0.9%). Vulvovaginitis was noted in 14%
(131/936) and encopresis in 2.3% (21/936). Enuresis according to age was reported
in 13% of 5-9 year olds, 14.7% of 10-16 year olds and 18.2% of 17-18 year olds
suspected of being abused. CONCLUSION: Prevalence of vulvovaginitis and enuresis
were increased, and encopresis was decreased in children with allegations of
sexual abuse when compared to the general pediatric population. Physicians should
continue to be aware of the possibility of the presence of these conditions in
children who have been sexually abused, and offer appropriate treatment.
PMID- 25127359
TI - Inhibition of glycogen synthase kinase-3beta attenuates glucocorticoid-induced
suppression of myogenic differentiation in vitro.
AB - Glucocorticoids are the only therapy that has been demonstrated to alter the
progress of Duchenne muscular dystrophy (DMD), the most common muscular dystrophy
in children. However, glucocorticoids disturb skeletal muscle metabolism and
hamper myogenesis and muscle regeneration. The mechanisms involved in the
glucocorticoid-mediated suppression of myogenic differentiation are not fully
understood. Glycogen synthase kinase-3beta (GSK-3beta) is considered to play a
central role as a negative regulator in myogenic differentiation. Here, we showed
that glucocorticoid treatment during the first 48 h in differentiation medium
decreased the level of phosphorylated Ser9-GSK-3beta, an inactive form of GSK
3beta, suggesting that glucocorticoids affect GSK-3beta activity. We then
investigated whether GSK-3beta inhibition could regulate glucocorticoid-mediated
suppression of myogenic differentiation in vitro. Two methods were employed to
inhibit GSK-3beta: pharmacological inhibition with LiCl and GSK-3beta gene
knockdown. We found that both methods resulted in enhanced myotube formation and
increased levels of muscle regulatory factors and muscle-specific protein
expression. Importantly, GSK-3beta inhibition attenuated glucocorticoid-induced
suppression of myogenic differentiation. Collectively, these data suggest the
involvement of GSK-3beta in the glucocorticoid-mediated impairment of myogenic
differentiation. Therefore, the inhibition of GSK-3beta may be a strategy for
preventing glucocorticoid-induced muscle degeneration.
PMID- 25127361
TI - A fluorescence color-encoded lipid-supported polymeric particle.
AB - Several fluorescent or luminescent organisms with biological, chemical, and
ecological diversity have been proposed as substitutes for use in new imaging and
diagnostic technologies. Inspired by these trends, we designed a synthetic
fluorescent light-encoding particulate to serve as a novel and prospective cancer
diagnostic imaging platform. The fluorescence-emitting particulate was used
practically for both in vitro and in vivo selective cancer diagnostic imaging.
PMID- 25127360
TI - Genetic characterization of Toxoplasma gondii isolates and toxoplasmosis
seroprevalence in stray cats of Izmir, Turkey.
AB - Currently, some Toxoplasma gondii genotypes are being associated with serious
clinical presentations. A recent report showing the Africa 1 genotype in two
local congenital toxoplasmosis cases acquired in Turkey formed the basis of this
study because atypical Africa 1 genotype is most frequently detected in animals
and patients from sub-Saharan Africa. Since stray cats are considered as the
linkage between wild life and urban life in T. gondii transmission, the present
study aimed to isolate and characterize T. gondii strains circulating in stray
cats of Izmir (Western Turkey). A secondary objective was to determine
toxoplasmosis seroprevalence in this cat population. Tissues obtained from 100
deceased stray cats were bioassayed and isolated strains were genotyped using 15
microsatellite markers. In addition, toxoplasmosis seroprevalence was analyzed in
1121 cat sera collected from several large veterinary clinics in Izmir. Among the
22 isolates, 19 were Type II (86.3%), two were Type III (9%) and one was Africa 1
genotype (4.5%). The overall seropositivity rates in cats were 42-48% and 33.4
34.4% according to IFA and ELISA, respectively. Seroprevalence in deceased cats
was significantly higher than in healthy cats (P = 0.0033). Finding both the
major clonal Type II lineage together with the Type III lineage also found in
Middle East, and an atypical genotype, Africa 1 appears consistent with the
specific geographic location of Turkey between three continents and raises the
possibility of transportation of these strains between continents through trade
routes or long distance migratory birds. In addition, the first large study of
toxoplasma seroprevalence in a stray cat population was also reported. The
relatively high seropositivity rates and the variety of T. gondii genotypes
confirm the local stray cat population as a risk factor for human toxoplasmosis
in Izmir.
PMID- 25127362
TI - Mineralization and drug release of hydroxyapatite/poly(l-lactic acid)
nanocomposite scaffolds prepared by Pickering emulsion templating.
AB - Biodegradable and bioactive nanocomposite (NC) biomaterials with controlled
microstructures and able to deliver special drugs have gained increasing
attention in bone tissue engineering. In this study, the hydroxyapatite
(HAp)/poly(l-lactic acid) (PLLA) NC scaffolds were facilely prepared using
solvent evaporation from templating Pickering emulsions stabilized with PLLA
modified HAp (g-HAp) nanoparticles. Then, in vitro mineralization experiments
were performed in a simulated body fluid (SBF) to evaluate the bioactivity of the
NC scaffolds. Moreover, in vitro drug release of the NC scaffolds using anti
inflammatory drug (ibuprofen, IBU) as the model drug was also investigated. The
results showed that the NC scaffolds possessed interconnected pore structures,
which could be modulated by varying the g-HAp nanoparticle concentration. The NC
scaffolds exhibited excellent bioactivity, since they induced the formation of
calcium-sufficient, carbonated apatite nanoparticles on the scaffolds after
mineralization in SBF for 3 days. The IBU loaded in the NC scaffolds showed a
sustained release profile, and the release kinetic followed the Higuchi model
with diffusion process. Thus, solvent evaporation based on Pickering emulsion
droplets is a simple and effective method to prepare biodegradable and bioactive
porous NC scaffolds for bone repair and replacement applications.
PMID- 25127364
TI - Delivery of antisense peptide nucleic acids to cells by conjugation with small
arginine-rich cell-penetrating peptide (R/W)9.
AB - Peptide nucleic acids (PNAs) are very attractive antisense and antigene agents,
but these molecules are not passively taken into cells. Here, using a functional
cell assay and fluorescent-based methods, we investigated cell uptake and
antisense activity of a tridecamer PNA that targets the HIV-1 polypurine tract
sequence delivered using the arginine-rich (R/W)9 peptide (RRWWRRWRR). At
micromolar concentrations, without use of any transfection agents, almost 80%
inhibition of the target gene expression was obtained with the conjugate in the
presence of the endosomolytic agent chloroquine. We show that chloroquine not
only induced escape from endosomes but also enhanced the cellular uptake of the
conjugate. Mechanistic studies revealed that (R/W)9-PNA conjugates were
internalized via pinocytosis. Replacement of arginines with lysines reduced the
uptake of the conjugate by six-fold, resulting in the abolition of intracellular
target inhibition. Our results show that the arginines play a crucial role in the
conjugate uptake and antisense activity. To determine whether specificity of the
interactions of arginines with cell surface proteoglycans result in the
internalization, we used flow cytometry to examine uptake of arginine- and lysine
rich conjugates in wild-type CHO-K1 and proteoglycan-deficient A745 cells. The
uptake of both conjugates was decreased by four fold in CHO-745 cells; therefore
proteoglycans promote internalization of cationic peptides, irrespective of the
chemical nature of their positive charges. Our results show that arginine-rich
cell-penetrating peptides, especially (R/W)9, are a promising tool for PNA
internalization.
PMID- 25127363
TI - Application of a combination of a knowledge-based algorithm and 2-stage screening
to hypothesis-free genomic data on irinotecan-treated patients for identification
of a candidate single nucleotide polymorphism related to an adverse effect.
AB - Interindividual variation in a drug response among patients is known to cause
serious problems in medicine. Genomic information has been proposed as the basis
for "personalized" health care. The genome-wide association study (GWAS) is a
powerful technique for examining single nucleotide polymorphisms (SNPs) and their
relationship with drug response variation; however, when using only GWAS, it
often happens that no useful SNPs are identified due to multiple testing
problems. Therefore, in a previous study, we proposed a combined method
consisting of a knowledge-based algorithm, 2 stages of screening, and a
permutation test for identifying SNPs. In the present study, we applied this
method to a pharmacogenomics study where 109,365 SNPs were genotyped using
Illumina Human-1 BeadChip in 168 cancer patients treated with irinotecan
chemotherapy. We identified the SNP rs9351963 in potassium voltage-gated channel
subfamily KQT member 5 (KCNQ5) as a candidate factor related to incidence of
irinotecan-induced diarrhea. The p value for rs9351963 was 3.31*10-5 in Fisher's
exact test and 0.0289 in the permutation test (when multiple testing problems
were corrected). Additionally, rs9351963 was clearly superior to the clinical
parameters and the model involving rs9351963 showed sensitivity of 77.8% and
specificity of 57.6% in the evaluation by means of logistic regression. Recent
studies showed that KCNQ4 and KCNQ5 genes encode members of the M channel
expressed in gastrointestinal smooth muscle and suggested that these genes are
associated with irritable bowel syndrome and similar peristalsis diseases. These
results suggest that rs9351963 in KCNQ5 is a possible predictive factor of
incidence of diarrhea in cancer patients treated with irinotecan chemotherapy and
for selecting chemotherapy regimens, such as irinotecan alone or a combination of
irinotecan with a KCNQ5 opener. Nonetheless, clinical importance of rs9351963
should be further elucidated.
PMID- 25127365
TI - Vitamin K2 biosynthetic enzyme, UBIAD1 is essential for embryonic development of
mice.
AB - UbiA prenyltransferase domain containing 1 (UBIAD1) is a novel vitamin K2
biosynthetic enzyme screened and identified from the human genome database.
UBIAD1 has recently been shown to catalyse the biosynthesis of Coenzyme Q10
(CoQ10) in zebrafish and human cells. To investigate the function of UBIAD1 in
vivo, we attempted to generate mice lacking Ubiad1, a homolog of human UBIAD1, by
gene targeting. Ubiad1-deficient (Ubiad1(-/-)) mouse embryos failed to survive
beyond embryonic day 7.5, exhibiting small-sized body and gastrulation arrest.
Ubiad1(-/-) embryonic stem (ES) cells failed to synthesize vitamin K2 but were
able to synthesize CoQ9, similar to wild-type ES cells. Ubiad1(+/-) mice
developed normally, exhibiting normal growth and fertility. Vitamin K2 tissue
levels and synthesis activity were approximately half of those in the wild-type,
whereas CoQ9 tissue levels and synthesis activity were similar to those in the
wild-type. Similarly, UBIAD1 expression and vitamin K2 synthesis activity of
mouse embryonic fibroblasts prepared from Ubiad1(+/-) E15.5 embryos were
approximately half of those in the wild-type, whereas CoQ9 levels and synthesis
activity were similar to those in the wild-type. Ubiad1(-/-) mouse embryos failed
to be rescued, but their embryonic lifespans were extended to term by oral
administration of MK-4 or CoQ10 to pregnant Ubiad1(+/-) mice. These results
suggest that UBIAD1 is responsible for vitamin K2 synthesis but may not be
responsible for CoQ9 synthesis in mice. We propose that UBIAD1 plays a pivotal
role in embryonic development by synthesizing vitamin K2, but may have additional
functions beyond the biosynthesis of vitamin K2.
PMID- 25127369
TI - The effects of musical practice on structural plasticity: the dynamics of grey
matter changes.
AB - Intensive training and the acquisition of expertise are known to bring about
structural changes in the brain. Musical training is a particularly interesting
model. Previous studies have reported structural brain modifications in the
auditory, motor and visuospatial areas of musicians compared with nonmusicians.
The main goal of the present study was to go one step further, by exploring the
dynamic of those structural brain changes related to musical experience. To this
end, we conducted a regression study on 44 nonmusicians and amateur musicians
with 0-26years of musical practice of a variety instruments. We sought first to
highlight brain areas that increased with the duration of practice and secondly
distinguish (thanks to an ANOVA analysis) brain areas that undergo grey matter
changes after only limited years of musical practice from those that require
longer practice before they exhibit changes. Results revealed that musical
training results a greater grey matter volumes in different brain areas for
musicians. Changes appear gradually in the left hippocampus and right middle and
superior frontal regions, but later also include the right insula and
supplementary motor area and left superior temporal, and posterior cingulate
areas. Given that all participants had the same age and that we controlled for
age and education level, these results cannot be ascribed to normal brain
maturation. Instead, they support the notion that musical training could induce
dynamic structural changes.
PMID- 25127366
TI - Dengue virus 2 American-Asian genotype identified during the 2006/2007 outbreak
in Piaui, Brazil reveals a Caribbean route of introduction and dissemination of
dengue virus in Brazil.
AB - Dengue virus (DENV) is the most widespread arthropod-borne virus, and the number
and severity of outbreaks has increased worldwide in recent decades. Dengue is
caused by DENV-1, DENV- 2, DENV-3 and DENV-4 which are genetically distant. The
species has been subdivided into genotypes based on phylogenetic studies. DENV-2,
which was isolated from dengue fever patients during an outbreak in Piaui, Brazil
in 2006/2007 was analyzed by sequencing the envelope (E) gene. The results
indicated a high similarity among the isolated viruses, as well as to other DENV
2 from Brazil, Central America and South America. A phylogenetic and
phylogeographic analysis based on DENV-2E gene sequences revealed that these
viruses are grouped together with viruses of the American-Asian genotype in two
distinct lineages. Our results demonstrate the co-circulation of two American
Asian genotype lineages in northeast Brazil. Moreover, we reveal that DENV-2
lineage 2 was detected in Piaui before it disseminated to other Brazilian states
and South American countries, indicating the existence of a new dissemination
route that has not been previously described.
PMID- 25127371
TI - Epilepsy, comorbid conditions in Canadian children: analysis of cross-sectional
data from cycle 3 of the National Longitudinal Study of Children and Youth.
AB - PURPOSE: The purpose of this study was to analyze national survey data to provide
estimates of prevalence of epilepsy and associated developmental disabilities and
comorbid conditions. METHODS: We analyzed data from Cycle 3 of Canada's National
Longitudinal Survey of Children and Youth. The NLSCY captured, socio-demographic
information, as well as age, sex, education, ethnicity, household income, chronic
health related conditions from birth to 15 years old. The main survey question
intended to identify "epilepsy", "cerebral palsy", "intellectual disability",
"learning disability", and "emotional and nervous difficulties" in the population
of children surveyed. Prevalence was based on the national cross-sectional sample
and used 1000 bootstrap weights to account for survey design factors. RESULTS:
Cycle 3 of the NLSCY had the largest number of patients with diagnosed epilepsy.
Prevalence figures (n/1000) for epilepsy and cerebral palsy (EPI_CP), epilepsy
and intellectual disability (EPI_ID), epilepsy and learning disability (EPI_LD),
and epilepsy and emotional nervous difficulties (EPI_EMO_NERV) were 1.1, 1.17,
2.58 and 1.34 respectively. Amongst children with epilepsy, 43.17% reported the
presence of one or more of the above comorbid conditions. CONCLUSION: These
results provide an initial prevalence estimate of comorbid conditions with
epilepsy in Canadian children. In a high proportion of children with epilepsy,
the PMK had reported at least one comorbid disorder. These findings carry
implications for health care utilization and long-term outcomes. We discuss
methodological aspects related to the ascertainment of epilepsy in both surveys,
and to the validity and implications of our findings.
PMID- 25127372
TI - The impact of web-based HOT (Healthy Outcomes for Teens) Project on risk for type
2 diabetes: a randomized controlled trial.
AB - BACKGROUND: The HOT (Healthy Outcome for Teens) Project is an innovative online
educational intervention for middle school children for prevention of diabetes
and obesity by balancing food intake with physical activity. The objective was to
improve knowledge, outcome expectations, self-efficacy, and self-reported food
intake and skills and to compare a passive online learning (POL) control group
with an active online learning (AOL) treatment group by implementing a social
cognitive theory (SCT)-grounded online intervention. SUBJECTS AND METHODS: In
total, 214 participants were recruited from three middle schools. Full data were
secured for 181 students. Six valid, reliable questionnaires were administered
online, pre/post, to both the AOL and POL groups to assess knowledge gain, self
reported intake, and meal planning skills, as well as change in SCT constructs.
RESULTS: Subjects in the AOL group improved significantly for all five categories
of planning a meal questionnaire (P=0.001) and also for outcome expectations for
exercise (P=0.001). At postintervention, no significant differences were found
for composite scores of exercise self-efficacy, weight efficacy lifestyle, and
rapid eating assessment plan questionnaires between AOL versus POL (by Mann
Whitney test). CONCLUSIONS: We conclude that teens participating in the AOL
version of the HOT Project intervention acquired skills for planning a meal and
improved outcome expectations for exercise.
PMID- 25127370
TI - Clinical correlates of graph theory findings in temporal lobe epilepsy.
AB - PURPOSE: Temporal lobe epilepsy (TLE) is considered a brain network disorder,
additionally representing the most common form of pharmaco-resistant epilepsy in
adults. There is increasing evidence that seizures in TLE arise from abnormal
epileptogenic networks, which extend beyond the clinico-radiologically determined
epileptogenic zone and may contribute to the failure rate of 30-50% following
epilepsy surgery. Graph theory allows for a network-based representation of TLE
brain networks using several neuroimaging and electrophysiologic modalities, and
has potential to provide clinicians with clinically useful biomarkers for
diagnostic and prognostic purposes. METHODS: We performed a review of the current
state of graph theory findings in TLE as they pertain to localization of the
epileptogenic zone, prediction of pre- and post-surgical seizure frequency and
cognitive performance, and monitoring cognitive decline in TLE. RESULTS: Although
different neuroimaging and electrophysiologic modalities have yielded
occasionally conflicting results, several potential biomarkers have been
characterized for identifying the epileptogenic zone, pre-/post-surgical seizure
prediction, and assessing cognitive performance. For localization, graph theory
measures of centrality have shown the most potential, including betweenness
centrality, outdegree, and graph index complexity, whereas for prediction of
seizure frequency, measures of synchronizability have shown the most potential.
The utility of clustering coefficient and characteristic path length for
assessing cognitive performance in TLE is also discussed. CONCLUSIONS: Future
studies integrating data from multiple modalities and testing predictive models
are needed to clarify findings and develop graph theory for its clinical utility.
PMID- 25127373
TI - Comparison of platelet serotonin transporter activity in subjects with severe
sleep bruxism and control.
AB - PURPOSE: The aim of this study was to evaluate the correlation between sleep
bruxism (SB) frequency and serotonin transporter (SERT)-driven serotonin (5-HT)
uptake in platelets. METHODS: Subjects were dental trainee residents and faculty
members of Okayama University Hospital who were aware of having severe or no SB.
SB frequency was assessed for 3-consecutive nights by a self-contained
electromyographic detector/analyzer, which indicated individual SB levels as one
of four grades (score 0, 1, 2 and 3). Subjects were classified as normal control
(NC) when SB scores indicated only 0 or 1 during the 3 nights, or as severe SB
for scores 2 or 3. Those subjects whose scores fluctuated from 0 to 3 during the
3 nights were omitted from further analysis. Fasting peripheral venous blood
samples were collected in the morning following the final SB assessment. Amounts
of SERTs proteins collected from peripheral platelets were quantified using
ELISA, and SERTs transport activity was assessed by uptake assay using [3H]-5-HT.
RESULTS: Thirteen severe SB subjects and 7 NC subjects were eligible. Gender
distribution, mean age, 5-HT concentration and total amounts of SERT protein in
platelets showed no significant differences between NC and severe SB (p=0.85: Chi
squared test; p=0.64, 0.26, 0.46: t-test). However, [3H]-5-HT uptake by platelets
was significantly greater in NC compared to severe SB subjects (12.79+/-1.97,
8.27+/-1.91 fmol/10(5) platelets/min, p<0.001, t-test). CONCLUSION: The results
of this pilot study suggest a possible correlation between peripheral platelet
serotonin transporter uptake ability and SB severity.
PMID- 25127374
TI - Nuclear mobility and activity of FOXA1 with androgen receptor are regulated by
SUMOylation.
AB - Forkhead box (FOX) protein A1 has been dubbed a pioneer transcription factor
because it binds target sites in DNA, thereby displacing nucleosomes to loosen
chromatin and facilitating steroid receptor DNA binding nearby. FOXA1 is an
important regulator of prostate development, collaborating with androgen receptor
(AR). Post-translational modifications regulating FOXA1 are thus far poorly
understood. SUMOylation, post-translational modification of proteins by small
ubiquitin-like modifier (SUMO) proteins, has emerged as an important regulatory
mechanism in transcriptional regulation. In this work, we show by SUMOylation
assays in COS-1 cells that the FOXA1 is modified at least in two of its three
lysines embedded in SUMOylation consensus, K6 and K389, in proximity to its
transactivation domains and K267 proximal to its DNA-binding domain. We also
provide evidence for SUMO-2/3 modification of endogenous FOXA1 in LNCaP prostate
cancer cells. Based on fluorescence recovery after photobleaching assays with
mCherry-fused FOXA1 and EGFP-fused AR in HEK293 cells, the presence of FOXA1
retards the nuclear mobility of agonist-bound AR. Interestingly, mutation of the
FOXA1 SUMOylation sites slows down the mobility of the pioneer factor, further
retarding the nuclear mobility of the AR. Chromatin immunoprecipitation and gene
expression assays suggest that the mutation enhances FOXA1's chromatin occupancy
as well as its activity on AR-regulated prostate-specific antigen (PSA) locus in
LNCaP cells. Moreover, the mutation altered the ability of FOXA1 to influence
proliferation of LNCaP cells. Taken together, these results strongly suggest that
the SUMOylation can regulate the transcriptional activity of FOXA1 with the AR.
PMID- 25127376
TI - Effect of different head and neck positions on behaviour, heart rate variability
and cortisol levels in lunged Royal Dutch Sport horses.
AB - Different head-and-neck positions (HNPs) are discussed in relation to potential
welfare issues. To evaluate the effect on welfare, seven Royal Dutch Sport horses
were studied in five predetermined HNPs: (1) unrestrained (HNP1); (2) neck
raised, bridge of nose around the vertical (HNP2); (3) neck lowered and
considerably flexed, bridge of nose pointing towards the chest (HNP4); (4) neck
raised and extended, bridge of nose in front of the vertical (HNP5), and (5) neck
lowered and flexed, bridge of nose pointing towards the carpus (HNP7). A
standardised exercise test (SET) of 34 min consisted of trot, canter and walk.
Behaviour was recorded with a pre-defined ethogram and R-R intervals measured
using telemetry. Cortisol concentrations were taken at the start, 5 and 30 min
after the SET. Behaviour around the SET was scored separately. Conflict
behaviours increased significantly during HNP2 when compared with HNP1, HNP4 and
HNP7 during the SET, and there was significant negative anticipation before HNP2
and HNP7. The heart rate variability (HRV) frequency domain for HNP2 showed a
significantly increased low frequency peak (LFpeak) compared with other HNPs, and
there was a decrease in very low frequency (VLF%) compared with HNP1. HNP4 showed
a significant increase in LF% and decrease in VLF% compared with HNP1. Saliva
cortisol concentrations were significantly increased in HNP2 at 5 and 30 min
after exercise. Increased conflict behaviour was mostly observed in HNP2, but
there was a raised HRV suggesting a sympathetic shift in HNP2 and HNP4, and
increased cortisol concentrations during HNP2 indicated a stress response.
PMID- 25127377
TI - Finite element analysis of three commonly used external fixation devices for
treating Type III pilon fractures.
AB - Pilon fractures are commonly caused by high energy trauma and can result in long
term immobilization of patients. The use of an external fixator i.e. the (1)
Delta, (2) Mitkovic or (3) Unilateral frame for treating type III pilon fractures
is generally recommended by many experts owing to the stability provided by these
constructs. This allows this type of fracture to heal quickly whilst permitting
early mobilization. However, the stability of one fixator over the other has not
been previously demonstrated. This study was conducted to determine the
biomechanical stability of these external fixators in type III pilon fractures
using finite element modelling. Three-dimensional models of the tibia, fibula,
talus, calcaneus, navicular, cuboid, three cuneiforms and five metatarsal bones
were reconstructed from previously obtained CT datasets. Bones were assigned with
isotropic material properties, while the cartilage was assigned as hyperelastic
springs with Mooney-Rivlin properties. Axial loads of 350 N and 70 N were applied
at the tibia to simulate the stance and the swing phase of a gait cycle. To
prevent rigid body motion, the calcaneus and metatarsals were fixed distally in
all degrees of freedom. The results indicate that the model with the Delta frame
produced the lowest relative micromovement (0.03 mm) compared to the Mitkovic
(0.05 mm) and Unilateral (0.42 mm) fixators during the stance phase. The highest
stress concentrations were found at the pin of the Unilateral external fixator
(509.2 MPa) compared to the Mitkovic (286.0 MPa) and the Delta (266.7 MPa)
frames. In conclusion, the Delta external fixator was found to be the most stable
external fixator for treating type III pilon fractures.
PMID- 25127375
TI - Lipocalin 2 is a regulator of macrophage polarization and NF-kappaB/STAT3 pathway
activation.
AB - Lipocalin 2 (Lcn2) has been previously characterized as an adipokine/cytokine and
implicated in obesity and inflammation. Herein, we investigated the role and
potential mechanism of Lcn2 in the regulation of macrophage polarization in
obesity-associated inflammation. We observed that Lcn2-/- mice displayed an up
regulation of expression of M1 macrophage marker Cd11c but a down-regulation of
M2 marker arginase 1 in adipose tissue and liver of mice upon a high-fat diet
feeding. Lcn2-deficient bone marrow-derived macrophages (BMDMs) were more
sensitive to lipopolysaccharide (LPS) stimulation, leading to a more profound up
regulation of expression of pro-inflammatory markers than wild-type (WT) BMDMs.
Accordingly, LPS stimulation elicited an increase in the activation of nuclear
factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), c-Jun, and
STAT3 signaling pathways as well as an up-regualtion of expression of NF-kappaB
and STAT3 target genes such as IL-1beta, IL-6, iNOS, and MCP-1 in Lcn2-/- BMDMs
compared with WT controls. Pre-treatment of recombinant Lcn2 attenuated LPS
stimulated degradation of IkappaBalpha and STAT3 phosphorylation as well as LPS
induced gene expression of IL-6 and iNOS in Lcn2-/- BMDMs. Moreover, the NFkappaB
inhibitor markedly blocked LPS-stimulated STAT3 phosphorylation in Lcn2-/- BMDMs.
These results together with the time course of Lcn2 secretion, NFkappaB and STAT3
phosphorylation in response to LPS stimulation, suggest that Lcn2 plays a role as
an anti-inflammatory regulator in macrophage activation via modulating a feed
forward activation of NFkappaB-STAT3 loop.
PMID- 25127379
TI - Impacts of groundwater discharge at Myora Springs (North Stradbroke Island,
Australia) on the phenolic metabolism of eelgrass, Zostera muelleri, and grazing
by the juvenile rabbitfish, Siganus fuscescens.
AB - Myora Springs is one of many groundwater discharge sites on North Stradbroke
Island (Queensland, Australia). Here spring waters emerge from wetland forests to
join Moreton Bay, mixing with seawater over seagrass meadows dominated by
eelgrass, Zostera muelleri. We sought to determine how low pH/high CO2 conditions
near the spring affect these plants and their interactions with the black
rabbitfish (Siganus fuscescens), a co-occurring grazer. In paired-choice feeding
trials S. fuscescens preferentially consumed Z. muelleri shoots collected nearest
to Myora Springs. Proximity to the spring did not significantly alter the carbon
and nitrogen contents of seagrass tissues but did result in the extraordinary
loss of soluble phenolics, including Folin-reactive phenolics, condensed tannins,
and phenolic acids by >=87%. Conversely, seagrass lignin contents were, in this
and related experiments, unaffected or increased, suggesting a shift in secondary
metabolism away from the production of soluble, but not insoluble,
(poly)phenolics. We suggest that groundwater discharge sites such as Myora
Springs, and other sites characterized by low pH, are likely to be popular
feeding grounds for seagrass grazers seeking to reduce their exposure to soluble
phenolics.
PMID- 25127380
TI - Orthodontic treatment of an adult patient with severe crowding and unilateral
missing premolars.
PMID- 25127378
TI - Quantifying metabolic heterogeneity in head and neck tumors in real time: 2-DG
uptake is highest in hypoxic tumor regions.
AB - PURPOSE: Intratumoral metabolic heterogeneity may increase the likelihood of
treatment failure due to the presence of a subset of resistant tumor cells. Using
a head and neck squamous cell carcinoma (HNSCC) xenograft model and a real-time
fluorescence imaging approach, we tested the hypothesis that tumors are
metabolically heterogeneous, and that tumor hypoxia alters patterns of glucose
uptake within the tumor. EXPERIMENTAL DESIGN: Cal33 cells were grown as xenograft
tumors (n = 16) in nude mice after identification of this cell line's metabolic
response to hypoxia. Tumor uptake of fluorescent markers identifying hypoxia,
glucose import, or vascularity was imaged simultaneously using fluorescent
molecular tomography. The variability of intratumoral 2-deoxyglucose (IR800-2-DG)
concentration was used to assess tumor metabolic heterogeneity, which was further
investigated using immunohistochemistry for expression of key metabolic enzymes.
HNSCC tumors in patients were assessed for intratumoral variability of (18)F
fluorodeoxyglucose ((18)F-FDG) uptake in clinical PET scans. RESULTS: IR800-2-DG
uptake in hypoxic regions of Cal33 tumors was 2.04 times higher compared to the
whole tumor (p = 0.0001). IR800-2-DG uptake in tumors containing hypoxic regions
was more heterogeneous as compared to tumors lacking a hypoxic signal.
Immunohistochemistry staining for HIF-1alpha, carbonic anhydrase 9, and ATP
synthase subunit 5beta confirmed xenograft metabolic heterogeneity. We detected
heterogeneous (18)F-FDG uptake within patient HNSCC tumors, and the degree of
heterogeneity varied amongst tumors. CONCLUSION: Hypoxia is associated with
increased intratumoral metabolic heterogeneity. (18)F-FDG PET scans may be used
to stratify patients according to the metabolic heterogeneity within their
tumors, which could be an indicator of prognosis.
PMID- 25127381
TI - Progressive slicing of second deciduous molars in a young patient with second
premolar agnesis.
PMID- 25127382
TI - Mini-implant-supported temporary pontics.
PMID- 25127383
TI - A rapid maxillary expander with differential opening.
PMID- 25127384
TI - Resin reinforcement: an alternative approach for direct bonding of molar tubes.
PMID- 25127385
TI - Scoring of ceramic bracket bases for easier debonding.
PMID- 25127386
TI - Removal of aqueous Hg(II) and Cr(VI) using phytic acid doped
polyaniline/cellulose acetate composite membrane.
AB - Conductive composite membrane-phytic acid (PA) doped polyaniline (PANI)/cellulose
acetate (CA) (PANI-PA/CA) was prepared in a simple and environmental-friendly
method, in which aniline was blended with CA/PA solution and polymerized before
the phase conversion. The resultant composite membranes were characterized by
SEM, EDX, FTIR-ATR, BET and electrical resistance measurements. When used as
adsorbent for Hg(II) and Cr(VI) ions, the prepared composite membrane exhibits
excellent adsorption capability. The adsorption of Hg(II) and Cr(VI) follows a
pseudo-second-order kinetic model and best fits the Langmuir isotherm model, with
the maximum adsorption capacity reaching 280.11 and 94.34 mg g(-1), respectively.
The heavy metal loaded composite membrane can be regenerated and reused after
treatment with acid or alkali solution, making it a promising and practical
adsorbent for Hg(II) and Cr(VI) removal. Tests with river water were also carried
out, indicating good performance and application.
PMID- 25127387
TI - Reaction of carbon tetrachloride with methane in a non-equilibrium plasma at
atmospheric pressure, and characterisation of the polymer thus formed.
AB - In this paper we focus on the development of a methodology for treatment of
carbon tetrachloride utilising a non-equilibrium plasma operating at atmospheric
pressure, which is not singularly aimed at destroying carbon tetrachloride but
rather at converting it to a non-hazardous, potentially valuable commodity. This
method encompasses the reaction of carbon tetrachloride and methane, with argon
as a carrier gas, in a quartz dielectric barrier discharge reactor. The reaction
is performed under non-oxidative conditions. Possible pathways for formation of
major products based on experimental results and supported by quantum chemical
calculations are outlined in the paper. We elucidate important parameters such as
carbon tetrachloride conversion, product distribution, mass balance and
characterise the chlorinated polymer formed in the process.
PMID- 25127388
TI - Specific and ultrasensitive ciprofloxacin detection by responsive photonic
crystal sensor.
AB - A new approach for specific and ultrasensitive measurement of ciprofloxacin has
been developed by integrating ternary complexes into responsive photonic crystal
(RPC). Tryptophan was first immobilized within the polyacrylamide hydrogel
substrates of RPC. The determination of ciprofloxacin was via the existence of
zinc(II) ions that function as a 'bridge' to form specific tryptophan-zinc(II)
ciprofloxacin complexes step by step, which resulted in a stepwise red-shift of
the diffraction wavelength. A maximum wavelength shift from 798 to 870 nm for
ciprofloxacin was observed when the RPC film was immersed in 10(-4)M
ciprofloxacin. A linear relationship has been obtained between the Deltalambda of
diffraction peak and logarithm of ciprofloxacin concentration at pH 5.0 in the
range of 10(-10) to 10(-4)M. And the least detectable concentration in present
work is about 5 * 10(-11)M. The results demonstrated that the as-designed ternary
complexes-based RPC sensor exhibited high sensitivity, satisfactory specificity
and excellent recoverability for sensing of ciprofloxacin in aqueous media and
were validated by detecting ciprofloxacin in the eye-drop sample.
PMID- 25127389
TI - Graphene oxide as an effective catalyst for wet air oxidation of phenol.
AB - The graphene oxide (GO) and chemically reduced graphene oxides, used as catalysts
in absence of any metals, were investigated in the catalytic wet air oxidation
(CWAO) of phenol in a batch reactor. The characterization of the materials was
measured with scanning electron microscopy (SEM), transmission electron
microscopy (TEM), Raman, fourier transform infrared spectroscopy (FT-IR) and X
ray photoelectron spectroscopy (XPS). The carbon materials exhibited good phenol
and total organic compounds (TOC) removals in the CWAO of phenol. The GO had the
highest catalytic activity, total phenol removal was achieved after 40 min, and
ca. 84% TOC removal was obtained after 120 min at reaction temperature of 155
degrees C, total pressure of 2.5 MPa and catalyst loading of 0.2 gL(-1).
PMID- 25127390
TI - What predicts the first peak of the knee adduction moment?
AB - BACKGROUND: The first peak of the knee adduction moment curve during walking has
been shown to be a good clinical surrogate measure of medial tibiofemoral joint
loading and osteoarthritis. Defining the relative contributions of the variables
that dictate the knee adduction moment, such as center of mass, center of
pressure, vertical ground reaction force, and knee adduction angle (i.e. lower
limb alignment), has not been formally investigated within the same cohort of
individuals. Therefore, the goal of this study was to determine which of these
variables is the biggest determinant of the first peak of knee adduction moment
curve. METHODS: Instrumented gait analysis was collected for 30 individuals.
Variables significantly correlated with the peak knee adduction moment were input
into a stepwise multi-variable linear regression model. RESULTS: The knee
adduction angle predicted 58% of the variance in the first peak knee adduction
moment and the vertical ground reaction force magnitude predicted the second most
variance (20%). CONCLUSIONS: The most effective way to modify the peak knee
adduction moment may be to change the knee adduction angle (e.g. off loader
brace), followed by changing the vertical magnitude of the ground reaction force
(e.g. cane use). CLINICAL RELEVANCE: Defining the major determinants of the knee
adduction moment may help guide clinicians in choosing conservative interventions
to reduce it in conditions such as medial tibiofemoral osteoarthritis.
PMID- 25127391
TI - Generation and behavior characterization of CaMKIIbeta knockout mice.
AB - The calcium/calmodulin-dependent protein kinase II (CaMKII) is abundant in the
brain, where it makes important contributions to synaptic organization and
homeostasis, including playing an essential role in synaptic plasticity and
memory. Four genes encode isoforms of CaMKII (alpha, beta, delta, gamma), with
CaMKIIalpha and CaMKIIbeta highly expressed in the brain. Decades of molecular
and cellular research, as well as the use of a large number of CaMKIIalpha mutant
mouse lines, have provided insight into the pivotal roles of CaMKIIalpha in brain
plasticity and cognition. However, less is known about the CaMKIIbeta isoform. We
report the development and extensive behavioral and phenotypic characterization
of a CaMKIIbeta knockout (KO) mouse. The CaMKIIbeta KO mouse was found to be
smaller at weaning, with an altered body mass composition. The CaMKIIbeta KO
mouse showed ataxia, impaired forelimb grip strength, and deficits in the
rotorod, balance beam and running wheel tasks. Interestingly, the CaMKIIbeta KO
mouse exhibited reduced anxiety in the elevated plus maze and open field tests.
The CaMKIIbeta KO mouse also showed cognitive impairment in the novel object
recognition task. Our results provide a comprehensive behavioral characterization
of mice deficient in the beta isoform of CaMKII. The neurologic phenotypes and
the construction of the genotype suggest the utility of this KO mouse strain for
future studies of CaMKIIbeta in brain structure, function and development.
PMID- 25127392
TI - A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic
myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic
leukemia.
AB - Aurora kinase overexpression has been observed in patients with hematologic
malignancies. MK-0457, a pan-aurora kinase inhibitor that also inhibits the ABL
T315I mutant, was evaluated to treat patients with chronic myelogenous leukemia
(CML) or Philadelphia chromosome (Ph+) acute lymphoblastic leukemia (ALL) with
the T315I mutation. Adults with Ph+ chronic phase (CP)-, accelerated phase (AP)-
or blast phase (BP)-CML, or ALL and documented BCR-ABL T315I mutation were
treated with a 5-day continuous infusion of MK-0457 administered every 14 days at
40 mg/m(2)/h, 32 mg/m(2)/h or 24 mg/m(2)/h. Fifty-two patients (CP, n=15; AP,
n=14; BP, n=11; Ph+ ALL, n=12) were treated. Overall, 8% of patients achieved
major cytogenetic response; 6% achieved unconfirmed complete or partial response;
39% had no response. Two patients (CP CML) achieved complete hematologic
response. No patients with advanced CML or Ph+ ALL achieved major hematologic
response. The most common adverse event (AE) was neutropenia (50%). The most
common grade 3/4 AEs were neutropenia (46%) and febrile neutropenia (35%). MK
0457 demonstrated minimal efficacy and only at higher, intolerable doses; lower
doses were tolerated and no unexpected toxicities were observed. These data will
assist in the development of future aurora kinase inhibitors and in the selection
of appropriate target patient populations.
PMID- 25127393
TI - Clinical features and treatment outcome in newly diagnosed Chinese patients with
multiple myeloma: results of a multicenter analysis.
AB - The aim of this study was to understand the clinical features and treatment
outcome of Chinese patients with multiple myeloma (MM). This retrospective study
enrolled 940 newly diagnosed inpatients (median age, 59 years; immunoglobulin
(Ig)D isotype, 6.5%) with complete follow-up data at three centers. In all, 85.8%
of patients were of Durie-Salmon stage III and 48.3% were of International
Staging System (ISS) stage III at diagnosis. Also, 9.6% of patients had
extramedullary plasmacytoma. Compared with IgG, IgD-type patients were diagnosed
at a younger age, and more patients were of ISS stage III, with hypercalcemia,
elevated levels of lactate dehydrogenase, hyperuricemia, renal dysfunction and
1q21 amplification (P=0.03). The overall survival (OS) benefit was more prominent
in IgG than in IgD when patients received bortezomib; however, they showed no
significant difference when they received older therapies such as melphalan
combined with prednisone or vincristine combined with adriamycin and
dexamethasone. Fluorescence in situ hybridization (FISH) results showed that
17.6% had 17p13 deletion. Conventional cytogenetics revealed that 13.3% were
hypodiploid and those cases had the worst survival, but hyperdiploid cases (9.3%)
did not show any survival benefit compared with those with a normal karyotype
(77.4%). Median OS and progression-free survival for all patients were 54 and 26
months, respectively. Significant factors for survival by multivariate analysis
were gender, ISS stage, number of FISH abnormalities and extramedullary disease.
MM in mainland China presents with different features, with patients being of
younger age and having higher risk and more survival benefit in IgG patients
receiving bortezomib.
PMID- 25127394
TI - Correlation of prostatic urethral angle with the severity of urinary symptom and
peak flow rate in men with small prostate volume.
AB - PURPOSE: To evaluate the effects of prostatic anatomical factors on male lower
urinary tract symptoms (LUTS) and the peak flow rate (Qmax) in patients with
small prostate volume (PV). MATERIALS AND METHODS: Records were obtained from a
prospectively maintained database of first-visit men with LUTS. Patients whose
total PV (TPV) was greater than 30 mL were excluded; 444 patients were enrolled
in the study. The TPV, transitional zone volume (TZV), transitional zone index
(TZI), intravesical prostatic protrusion (IPP), and prostatic urethral angle
(PUA) were measured by transrectal ultrasonography. LUTS were evaluated using the
International Prostate Symptom Score (IPSS) and the Overactive Bladder Symptom
Score (OABSS) questionnaires. Uroflowmetric measurements were also made. RESULTS:
PUA (r = 0.269, P<0.001), TZV (r = 0.160, P<0.001), and TZI (r = 0.109, P =
0.022) significantly correlated with the IPSS. Qmax (r = -0.334, P<0.001) and
OABSS (r = 0.211, P<0.001) correlated only with PUA. In a multivariate regression
analysis, PUA and age were independently associated with IPSS, OABSS, and Qmax.
For IPSS of 20 or greater, the area under the ROC curve (AUC) of PUA was 0.667
and the cut-off value was 43.7 degrees . When Qmax was 10 mL/s or less, the AUC
of PUA was 0.664 and the cut-off value was 43.5 degrees . CONCLUSIONS: PUA has a
significant association with symptom severity and Qmax among prostatic anatomical
factors analyzed in men with LUTS and small PV. PUA should be considered as an
important clinical factor in male LUTS management. Furthermore, the impact of PUA
on response to medical treatment and disease progression needs to be
investigated.
PMID- 25127395
TI - A simple efficient synthesis and biological evaluation of 3-O-ethylascorbic acid.
AB - A single-step synthesis of 3-O-ethyl-l-ascorbic acid was performed without the
induction of protecting groups. Sodium l-ascorbate reacted with ethyl bromide in
DMSO to give 3-O-ethylascorbic acid in a yield of 51.0%. 3-O-Ethylascorbic acid
enhanced dibutyryl cyclic AMP-induced neurite outgrowth in PC12 cells.
PMID- 25127396
TI - Socioeconomic dynamics of gender disparity in childhood immunization in India,
1992-2006.
AB - BACKGROUND: Recent evidence indicated that gender disparity in child health is
minimal and narrowed over time in India. However, considering the geographical
and socio-cultural diversity in India, the gender gap may persist across
disaggregated socioeconomic context which may be masked by average level. This
study examines the dynamics of gender disparity in childhood immunization across
regions, residence, wealth, caste and religion in India during 1992-2006. METHOD:
We used multi-waves of the cross-sectional data of National Family Health Survey
conducted in India between 1992-93 and 2005-06. Gender disparity ratio was used
to measure the gender gap in childhood immunization across the selected
socioeconomic characteristics. Multinomial regression analysis was used to
examine the gender gap after accounting for other covariates. RESULT: Results
indicate that, at aggregate level, gender disparity in full immunization is
minimal and has stagnated during the study period. However, gender disparity-
disfavouring female children--becomes apparent across the regions, poor
households, and religion--particularly among Muslims. Adjusted gender disparity
ratio indicates that, full immunization is lower among female than male children
of the western region, poor household and among Muslims. Between 1992-93 and 2005
06, the disparity in full immunization had narrowed in the northern region
whereas it had, astonishingly, increased in some of the western and southern
states of the country. CONCLUSION: Our findings emphasize the need to integrate
gender issues in the ongoing immunization programme in India, with particular
attention to urban areas, developed states, and to the Muslim community.
PMID- 25127398
TI - Climate change sensitivity index for Pacific salmon habitat in southeast Alaska.
AB - Global climate change may become one of the most pressing challenges to Pacific
Salmon conservation and management for southeast Alaska in the 21st Century.
Predicted hydrologic change associated with climate change will likely challenge
the ability of specific stocks to adapt to new flow regimes and resulting shifts
in spawning and rearing habitats. Current research suggests egg-to-fry survival
may be one of the most important freshwater limiting factors in Pacific Salmon's
northern range due to more frequent flooding events predicted to scour eggs from
mobile spawning substrates. A watershed-scale hydroclimatic sensitivity index was
developed to map this hypothesis with an historical stream gauge station dataset
and monthly multiple regression-based discharge models. The relative change from
present to future watershed conditions predicted for the spawning and incubation
period (September to March) was quantified using an ensemble global climate model
average (ECHAM5, HadCM3, and CGCM3.1) and three global greenhouse gas emission
scenarios (B1, A1B, and A2) projected to the year 2080. The models showed the
region's diverse physiography and climatology resulted in a relatively
predictable pattern of change: northern mainland and steeper, snow-fed
mountainous watersheds exhibited the greatest increases in discharge, an earlier
spring melt, and a transition into rain-fed hydrologic patterns. Predicted
streamflow increases for all watersheds ranged from approximately 1-fold to 3
fold for the spawning and incubation period, with increased peak flows in the
spring and fall. The hydroclimatic sensitivity index was then combined with an
index of currently mapped salmon habitat and species diversity to develop a
research and conservation priority matrix, highlighting potentially vulnerable to
resilient high-value watersheds. The resulting matrix and observed trends are put
forth as a framework to prioritize long-term monitoring plans, mitigation
experiments, and finer-scale climate impact and adaptation studies.
PMID- 25127397
TI - Association between domestic violence and HIV serostatus among married and
formerly married women in Kenya.
AB - The prevalence of both domestic violence (DV) and HIV among Kenyan women is known
to be high, but the relationship between them is unknown. Nationally
representative cross-sectional data from married and formerly married (MFM) women
responding to the Kenya Demographic and Health Survey 2008/2009 were analyzed
adjusting for complex survey design. Multivariable logistic regressions were used
to assess the covariate-adjusted associations between HIV serostatus and any
reported DV as well as four constituent DV measures: physical, emotional, sexual,
and aggravated bodily harm, adjusting for covariates entered into each model
using a forward stepwise selection process. Covariates of a priori interest
included those representing marriage history, risky sexual behavior, substance
use, perceived HIV risk, and sociodemographic characteristics. The prevalence of
HIV among MFM women was 10.7% (any DV: 13.1%, no DV: 8.6%); overall prevalence of
DV was 43.4%. Among all DV measures, only physical DV was associated with HIV
(11.9%; adjusted odds ratio: 2.01, p <.05). Efforts by the government and women's
groups to monitor and improve policies to reduce DV, such as the Sexual Offences
Act of 2006, are urgently needed to curb HIV, as are policies that seek to
provide DV counseling and treatment to MFM women.
PMID- 25127399
TI - Benefit of shading by nurse plant does not change along a stress gradient in a
coastal dune.
AB - The proximity of adult neighbors often increases the performance of woody
seedlings under harsh environmental conditions but this nurse plant effect
becomes less intense when abiotic stress is alleviated, as predicted by the
stress gradient hypothesis (SGH). Although some studies have tested how the net
nurse effect is changed by stress, few studies have tested how the mechanism that
drives the facilitative effect of nurse responds to changes in stress. We
conducted field experiments in a subtropical coastal dune to test if shading
drives the known nurse effect of adults of the tree Guapira opposita on seedling
performance of another tree species, Ternstroemia brasiliensis. We transplanted
T. brasiliensis seedlings to three neighbor environments: under a G. opposita
crown, under artificial shade and without neighbor as a control. Furthermore,
assuming that proximity to the seashore correlates with stress intensity, we
tested if the potential shade-driven facilitation became less intense as stress
decreased. Regardless of the proximity to the seashore, after a year, the
survival of T. brasiliensis seedlings was twice as high when the seedlings were
under G. opposita or under artificial shade compared to the control, indicating
that the nurse effect is driven by shade and that this facilitation mechanism is
constant along the stress gradient. However, G. opposita and artificial shade had
a negative effect on seedlings growth. Overall, our results showed that the
facilitation mechanism behind the nurse effect did not wane as the stress was
reduced. Furthermore, in spite of the potential costs in terms of biomass
production, our study highlights the potential of nurse plants and artificial
shade as techniques to improve the survival of transplanted seedlings used in the
restoration of degraded shrubland coastal dunes.
PMID- 25127400
TI - Use of cloneable peptide-MBP fusion protein as a mimetic coating antigen in the
standardized immunoassay for mycotoxin ochratoxin A.
AB - The quality of mycotoxin conjugates is essential to the development of
reliability of immunoassays for mycotoxins. However, conventional mycotoxin
conjugates are usually synthesized by chemical methods, which are harmful to the
environment and yield unwanted cross-reactions. In this study, using ochratoxin A
(OTA) as a model system, a selected OTA mimotope (phage-displayed peptide) that
specifically binds to anti-OTA antibody was expressed as soluble and monovalent
fusions to maltose binding protein (MBP). These prepared fusion proteins can
serve as a mimetic coating antigen in both a quantitative chemiluminescent enzyme
linked immunoassay (CLEIA) and a qualitative dot immunoassay for OTA. One of the
prepared mimetic coating antigen (L12-206-MBP)-based CLEIAs exhibited a half
inhibition concentration (IC50) of 0.82 ng/mL and a working range of 0.30-2.17
ng/mL, which resemble those of the conventional OTA-OVA conjugate-based
immunoassay. The dot immunoassay developed with both the OTA-OVA conjugate and
the mimetics showed identical visual cutoff values of 5 ng/mL. The mimetic
coating antigen proposed here is an OTA-free product and can be prepared
reproducibly as a homogeneous product and facilitates standardization of
immunoassays for the mycotoxin OTA.
PMID- 25127401
TI - Chelation gradients for investigation of metal ion binding at silica surfaces.
AB - Centimeter-long surface gradients in bi- and tridentate chelating agents have
been formed via controlled rate infusion, and the coordination of Cu(2+) and
Zn(2+) to these surfaces has been examined as a function of distance by X-ray
photoelectron spectroscopy (XPS). 3-(Trimethoxysilylpropyl)ethylenediamine and 3
(trimethoxysilylpropyl)diethylenetriamine were used as precursor silanes to form
the chelation gradients. When the gradients were exposed to a metal ion solution,
a series of coordination complexes formed along the length of the substrate. For
both chelating agents at the three different concentrations studied, the amine
content gradually increased from top to bottom as expected for a surface chemical
gradient. While the Cu 2p peak area had nearly the same profile as nitrogen, the
Zn 2p peak area did not and exhibited a plateau along much of the gradient. The
normalized nitrogen-to-metal peak area ratio (N/M) was found to be highly
dependent on the type of ligand, its surface concentration, and the type of metal
ion. For Cu(2+), the N/M ratio ranged from 8 to 11 on the diamine gradient and
was ~4 on the triamine gradient, while for Zn(2+), the N/M ratio was 4-8 on
diamine and 5-7 on triamine gradients. The extent of protonation of amine groups
was higher for the diamine gradients, which could lead to an increased N/M ratio.
Both 1:1 and 1:2 ligand/metal complexes along with dinuclear complexes are
proposed to form, with their relative amounts dependent on the ligand, ligand
density, and metal ion. Collectively, the methods and results described herein
represent a new approach to study metal ion binding and coordination on surfaces,
which is especially important to the extraction, preconcentration, and separation
of metal ions.
PMID- 25127403
TI - Be it ever so humble...
PMID- 25127402
TI - Transcriptional landscape of glomerular parietal epithelial cells.
AB - Very little is known about the function of glomerular parietal epithelial cells
(PECs). In this study, we performed genome-wide expression analysis on PEC
enriched capsulated vs. PEC-deprived decapsulated rat glomeruli to determine the
transcriptional state of PECs under normal conditions. We identified hundreds of
differentially expressed genes that mapped to distinct biologic modules including
development, tight junction, ion transport, and metabolic processes. Since
developmental programs were highly enriched in PECs, we characterized several of
their candidate members at the protein level. Collectively, our findings confirm
that PECs are multifaceted cells and help define their diverse functional
repertoire.
PMID- 25127404
TI - Remodeling a broken system through hospital-payer partnerships.
AB - One way to fix our broken system is to strengthen hospital-payer partnerships,
which will help shift caregiver focus from volume to value.
PMID- 25127406
TI - Dose and timing of prenatal tobacco exposure: threats to early child development.
PMID- 25127407
TI - Dynamic analysis of a needle insertion for soft materials: Arbitrary Lagrangian
Eulerian-based three-dimensional finite element analysis.
AB - BACKGROUND: Our goal was to develop a three-dimensional finite element model that
enables dynamic analysis of needle insertion for soft materials. To demonstrate
large deformation and fracture, we used the arbitrary Lagrangian-Eulerian (ALE)
method for fluid analysis. We performed ALE-based finite element analysis for 3%
agar gel and three types of copper needle with bevel tips. METHODS: To evaluate
simulation results, we compared the needle deflection and insertion force with
corresponding experimental results acquired with a uniaxial manipulator. We
studied the shear stress distribution of agar gel on various time scales.
RESULTS: For 30 degrees , 45 degrees , and 60 degrees , differences in
deflections of each needle between both sets of results were 2.424, 2.981, and
3.737mm, respectively. For the insertion force, there was no significant
difference for mismatching area error (p<0.05) between simulation and
experimental results. CONCLUSIONS: Our results have the potential to be a
stepping stone to develop pre-operative surgical planning to estimate an optimal
needle insertion path for MR image-guided microwave coagulation therapy and for
analyzing large deformation and fracture in biological tissues.
PMID- 25127405
TI - Effect of nicotine patches in pregnancy on infant and maternal outcomes at 2
years: follow-up from the randomised, double-blind, placebo-controlled SNAP
trial.
AB - BACKGROUND: The SNAP (Smoking and Nicotine in Pregnancy) trial compared nicotine
replacement therapy (NRT) patches with placebo in pregnant smokers; although NRT
doubled cessation rates in the first 4 weeks, by delivery no differences in
maternal smoking or birth outcomes were noted. As a result, NRT used in standard
doses during pregnancy is considered ineffective for smoking cessation.
Subsequent effects of NRT on the children of treated mothers are unknown because
no trials have investigated the effect of gestational NRT use beyond birth. To
assess whether NRT use in pregnancy might cause harm to infants, we aimed to
compare effects of NRT and placebo on infant development 2 years after delivery.
METHODS: 1050 pregnant smokers aged 16-45 years, at 12-24 weeks' gestation, and
smoking at least five cigarettes per day were recruited from seven hospitals in
England between May 1, 2007, and Feb 26, 2010, and followed up until their
infants were 2 years old. Participants were randomly assigned (1:1) to receive up
to 8-weeks treatment with NRT (15 mg/16 h transdermal patches) or identically
packaged and visually matched placebo patches (all patches manufactured by and
purchased at market rate from United Pharmaceuticals, Amman, Jordan), issued as
two 4-week supplies (521 for NRT group, 529 for placebo group) [Corrected].
Randomisation was stratified by site with participants, health-care
professionals, and research staff masked to treatment allocation. The primary
results for participants and infants at delivery were published in 2012; we
present results from the trial cohort 2 years after birth. After delivery,
questionnaires were posted to participants and, if there was no response, to
family physicians. The primary outcome at 2 years was infants' survival without
developmental impairment (ie, no disability or problems with behaviour or
development). Treatment groups were compared on an intention-to-treat basis. The
trial is registered with Controlled-Trials.com, number ISRCTN07249128. FINDINGS:
Questionnaires were returned at 2 years for 891 (88%) of 1010 live singleton
births (445 of (88%) 503 given NRT and 446 (88%) of 507 given placebo). Because
of missing data, developmental outcomes, including four infant deaths, were
documented for 888 of (88%) 1010 singleton infants; 445 (88%) of 503 infants in
NRT group and 443 (87%) of 507 infants in placebo. In the NRT group, 323 (73%) of
445 infants had no impairment compared with 290 (65%) of 443 infants in the
placebo group (odds ratio [OR] 1.40, 95% CI 1.05-1.86, p=0.023). At 2 years, 15
(3%) of 521 mothers in the NRT group and nine (2%) of 529 mothers in the placebo
groups self-reported prolonged smoking abstinence since a quit date set in
pregnancy (OR 1.71, 95% CI 0.74-3.94, p=0.20). Adverse events were not collected
after delivery, but previously reported adverse pregnancy and birth outcomes were
similar in the two groups. INTERPRETATION: Infants born to women who used NRT for
smoking cessation in pregnancy were more likely to have unimpaired development.
NRT had no effect on prolonged abstinence from smoking but did cause a temporary
doubling of smoking cessation shortly after randomisation during pregnancy, which
could explain findings. If findings are confirmed by subsequent research, this
has potential implications for the management of smoking in pregnancy. FUNDING:
National Institute for Health Research Health Technology Assessment Programme.
PMID- 25127408
TI - Locally linear representation Fisher criterion based tumor gene expressive data
classification.
AB - Tumor gene expressive data are characterized by a large amount of genes with only
a small amount of observations, which always appear with high dimensionality. So
it is necessary to reduce the dimensionality before identifying their genre. In
this paper, a discriminant manifold learning method, named locally linear
representation Fisher criterion (LLRFC), is applied to extract features from
tumor gene expressive data. In LLRFC, an inter-class graph and an intra-class
graph are constructed based on their genre information, where any tumor gene
expressive data in the inter-class graph should select k nearest neighbors with
different class labels and in the intra-class graph the k nearest neighbors for
any tumor gene expressive data must be sampled from those with the same class.
And then the locally least linear reconstruction is introduced to optimize the
corresponding weights in both graphs. Moreover, a Fisher criterion is modeled to
explore a low dimensional subspace where the reconstruction errors in the inter
class graph can be maximized and the reconstruction errors in the intra-class
graph can be minimized, simultaneously. Experiments on some benchmark tumor gene
expressive data have been conducted with some related algorithms, by which the
proposed LLRFC has been validated to be efficient.
PMID- 25127409
TI - Automated diagnosis of Age-related Macular Degeneration using greyscale features
from digital fundus images.
AB - Age-related Macular Degeneration (AMD) is one of the major causes of vision loss
and blindness in ageing population. Currently, there is no cure for AMD, however
early detection and subsequent treatment may prevent the severe vision loss or
slow the progression of the disease. AMD can be classified into two types: dry
and wet AMDs. The people with macular degeneration are mostly affected by dry
AMD. Early symptoms of AMD are formation of drusen and yellow pigmentation. These
lesions are identified by manual inspection of fundus images by the
ophthalmologists. It is a time consuming, tiresome process, and hence an
automated diagnosis of AMD screening tool can aid clinicians in their diagnosis
significantly. This study proposes an automated dry AMD detection system using
various entropies (Shannon, Kapur, Renyi and Yager), Higher Order Spectra (HOS)
bispectra features, Fractional Dimension (FD), and Gabor wavelet features
extracted from greyscale fundus images. The features are ranked using t-test,
Kullback-Lieber Divergence (KLD), Chernoff Bound and Bhattacharyya Distance
(CBBD), Receiver Operating Characteristics (ROC) curve-based and Wilcoxon ranking
methods in order to select optimum features and classified into normal and AMD
classes using Naive Bayes (NB), k-Nearest Neighbour (k-NN), Probabilistic Neural
Network (PNN), Decision Tree (DT) and Support Vector Machine (SVM) classifiers.
The performance of the proposed system is evaluated using private (Kasturba
Medical Hospital, Manipal, India), Automated Retinal Image Analysis (ARIA) and
STructured Analysis of the Retina (STARE) datasets. The proposed system yielded
the highest average classification accuracies of 90.19%, 95.07% and 95% with 42,
54 and 38 optimal ranked features using SVM classifier for private, ARIA and
STARE datasets respectively. This automated AMD detection system can be used for
mass fundus image screening and aid clinicians by making better use of their
expertise on selected images that require further examination.
PMID- 25127411
TI - Multifunctional 1D magnetic and fluorescent nanoparticle chains for enhanced MRI,
fluorescent cell imaging, and combined photothermal/chemotherapy.
AB - While the assembled 1D magnetic nanoparticle (NP) chains have demonstrated
synergistic magnetic effects from the individual NPs, it is essential to prepare
new 1D NP chains that can combine the magnetism with other important material
properties for multifunctional applications. This paper reports the fabrication
and multifunctional investigation of a new type of 1D NP chains that combine the
magnetic properties with fluorescent properties, photothermal conversion ability,
and drug carrier function. The building block NPs are composed of magnetic
Fe(3)O(4) nanocrystals clustered in the core and fluorescent carbon dots embedded
in the mesoporous carbon shell with hydroxyl/carboxyl groups anchored on their
surface. These NPs can assemble under the induction of external magnetic field
and form stable 1D NP chains of diameter ~ 90 nm and length ~ 3 MUm via the
hydrogen bonding and pi-pi stacking linkage of the carbon shell. The resulted 1D
hybrid NP chains not only demonstrate much higher magnetic resonance imaging
(MRI) contrasting ability than the dispersed building block NPs, but also enter
into intracellular region and light up the B16F10 cells under a laser excitation
with strong and stable fluorescence. While the mesoporous carbon shell provides
high drug loading capacity, the embedded fluorescent carbon dots convert near
infrared (NIR) light to heat, and hence kill the tumor cells efficiently and
enhance the drug release rate to further improve the therapeutic efficacy under
NIR irradiation. Such designed 1D magnetic-fluorescent hybrid NP chains with
enhanced MRI contrast, fluorescent imaging ability, and combined chemo
/photothermal therapeutic ability have great potential for various biomedical
applications.
PMID- 25127412
TI - Lactic acid production with undefined mixed culture fermentation of potato peel
waste.
AB - Potato peel waste (PPW) as zero value byproduct generated from food processing
plant contains a large quantity of starch, non-starch polysaccharide, lignin,
protein, and lipid. PPW as one promising carbon source can be managed and
utilized to value added bioproducts through a simple fermentation process using
undefined mixed cultures inoculated from wastewater treatment plant sludge. A
series of non-pH controlled batch fermentations under different conditions such
as pretreatment process, enzymatic hydrolysis, temperature, and solids loading
were studied. Lactic acid (LA) was the major product, followed by acetic acid
(AA) and ethanol under fermentation conditions without the presence of added
hydrolytic enzymes. The maximum yields of LA, AA, and ethanol were respectively,
0.22 g g(-1), 0.06 g g(-1), and 0.05 g g(-1). The highest LA concentration of
14.7 g L(-1) was obtained from a bioreactor with initial solids loading of 60 g
L(-1) at 35 degrees C.
PMID- 25127410
TI - The proteasome complex and the maintenance of pluripotency: sustain the fate by
mopping up?
AB - The proteasome is a multi-enzyme complex responsible for orchestrating protein
quality control by degrading misfolded, damaged, abnormal and foreign proteins.
Studies related to the association of the proteasomal system in the preservation
of self-renewal in both human and mouse pluripotent cells are sparse, and
therefore a clear indication of the emergence of a new and important field of
research. Under specific conditions the standard proteasome switches to the newly
synthesized immunoproteasome, a catalytically active protein chamber also
involved in the regulation of protein homeostasis, cell signaling and gene
expression. Herein we review recent data to help elucidate and highlight the
pivotal role of the proteasome complex, constitutive as well as inducible, in the
regulation of self-renewal, pluripotency and differentiation of both embryonic
and induced pluripotent stem cells. The proteasome that is endowed with enhanced
proteolytic activity maintains self-renewal by regulating gene expression. In
addition to protein degradation, the proteasome activator PA28, compartments of
the 19S regulatory particle and key members of the ubiquitin pathway dictate the
fate of a pluripotent stem cell. We anticipate that our observations will
stimulate active research in this new and emerging theme related to stem cell
biology, disease and regenerative medicine.
PMID- 25127413
TI - Intraoperative high-field MRI for transsphenoidal reoperations of nonfunctioning
pituitary adenoma.
AB - OBJECT: The loss of anatomical landmarks, frequently invasive tumor growth, and
tissue changes make transsphenoidal reoperation of nonfunctioning pituitary
adenomas (NFAs) challenging. The use of intraoperative MRI (iMRI) may lead to
improved results. The goal of this retrospective study was to evaluate the impact
of iMRI on transsphenoidal reoperations for NFA. METHODS: Between September 2002
and July 2012, 109 patients underwent reoperations in which 111 transsphenoidal
procedures were performed and are represented in this study. A 1.5-T Magnetom
Sonata Maestro Class scanner (Siemens) was used for iMRI. Follow-up iMRI scans
were acquired if gross-total resection (GTR) was suspected or if no further
removal seemed possible. RESULTS: Surgery was performed for tumor persistence and
regrowth in 26 (23%) and 85 (77%) patients, respectively. On the initial iMRI
scans, GTR was confirmed in 19 (17%) patients. Remnants were located as follows:
65 in the cavernous sinus (71%), 35 in the suprasellar space (38%), 9 in the
retrosellar space (10%). Additional resection was possible in 62 (67%) patients,
resulting in a significant volume reduction and increased GTR rate (49%). The GTR
rates of invasive tumors on initial iMRI and postoperative MRI (poMRI) were 7%
and 25%, respectively. Additional remnant resection was possible in 64% of the
patients. Noninvasive tumors were shown to be totally resected on the initial
iMRI in 31% of cases. After additional resection for 69% of the procedures, the
GTR rate on poMRI was 75%. Transcranial surgery to resect tumor remnants was
indicated in 5 (5%), and radiotherapy was performed in 29 (27%) patients. After
GTR, no recurrence was detected during a mean follow-up of 2.2 +/- 2.1 years.
CONCLUSIONS: The use of iMRI in transsphenoidal reoperations for NFA leads to
significantly higher GTR rates. It thus prevents additional operations and
reduces the number of tumor remnants. The complication rates do not exceed the
incidences reported in the literature for primary transsphenoidal surgery. If
complete tumor resection is not possible, iMRI guidance can facilitate tumor
volume reduction.
PMID- 25127414
TI - Association of genetic variants in the retinoblastoma binding protein 6 gene with
the risk of glioma: a case-control study in a Chinese Han population.
AB - OBJECT: The retinoblastoma binding protein 6 (RBBP6) gene plays an important role
in the induction of apoptosis and regulation of the cell cycle, and interacts
with both p53 and retinoblastoma protein in carcinogenesis. Recently, many
studies investigating the function of the RBBP6 gene, including its roles in lung
cancer and breast cancer, have been reported. However, the association between
RBBP6 variants and glioma was unknown. Therefore, to uncover the association
between single nucleotide polymorphisms (SNPs) of RBBP6 and glioma, a hospital
based case-control study was performed in a Chinese Han population. METHODS: Ten
common tagging SNPs of the RBBP6 gene (covering 100% of all SNPs) were genotyped
with the Sequenom MassARRY iPLEX platform, including 992 cases and 1008 controls,
according to the HapMap database based on a pairwise linkage disequilibrium r(2)
threshold of 0.8, minor allele frequency of 0.05, and Hardy-Weinberg equilibrium
of 0.05. RESULTS: The authors found that 4 SNPs were significantly associated
with glioma (rs2033214, p = 0.013, adjusted OR 2.46, 95% CI 1.18-5.14;
rs11860248, p = 8.64 * 10-(6), adjusted OR 1.59, 95% CI 1.23-2.05; rs9933544, p =
3.65 * 10(-4), adjusted OR 1.39, 95% CI 1.13-1.87; rs13332653, p = 0.004,
adjusted OR 1.49, 95% CI 1.14-1.95). Stratification analyses revealed that
rs2033214 was only significantly associated with low-grade gliomas; rs9933544 and
rs13332653 were only significantly associated with glioblastoma multiforme; and
rs11860248 was significantly associated with both low-grade gliomas and
glioblastoma multiforme, compared with the common wild-type homozygous genotype.
Further stratified analysis revealed that rs11860248 was more pronounced in
certain subgroups: adults, males, histological types, and family history of
cancer. What's more, the haplotype and diplotype analyses consistently revealed
that the subjects carrying 1 copy of haplotype CCGCC had a 53% increased glioma
risk compared with their corresponding noncarriers (p = 0.018, adjusted OR 1.53,
95% CI 1.08-2.17). CONCLUSIONS: The authors' results suggested that RBBP6 gene
variants are associated with glioma and contribute to glioma susceptibility,
which was first reported elsewhere. Individuals with the so-called risk alleles
might have an increased risk of glioma. These results might provide new insight
into the occurrence of glioma.
PMID- 25127415
TI - Outcome in adult patients with hemorrhagic moyamoya disease after combined
extracranial-intracranial bypass.
AB - OBJECT: The outcome of patients with hemorrhagic moyamoya disease (MMD) after
cerebral revascularization is uncertain. The purpose of this study was to
delineate the efficacy of this surgical method in the treatment of hemorrhagic
MMD. METHODS: Between January 2007 and August 2011, a consecutive cohort of 113
patients with hemorrhagic MMD was enrolled into this prospective single-center
cohort study. The surgical method was combined direct and indirect bypass. The
cumulative probability of the primary end point (all stroke and deaths from
surgery through 30 days after surgery and ipsilateral recurrent hemorrhage
afterward) was analyzed. The angiographic outcome was measured by the following
parameters: bypass patency, reduction of basal MMD vessels, improved degree of
dilation, and branch extension of the anterior choroidal and posterior
communicating arteries (AChA-PCoA). RESULTS: Of the 113 enrolled cases, CT scans
revealed pure intraventricular hemorrhage (IVH) in 63 cases (55.7%), pure
intracranial hemorrhage (ICH) in 14 cases (12.4%), and ICH with IVH in 36 cases
(31.9%). In 74 of 113 hemorrhagic hemispheres (65.5%), the AChA-PCoA was
extremely dilated with extensive branches beyond the choroidal fissure. A total
of 114 surgeries were performed. No patient suffered ischemic or hemorrhagic
stroke through 30 days after surgery. Ipsilateral rebleeding occurred in 5
patients, 4 of whom died of the rebleeding event. The cumulative probability of
the primary end point was 0% at 1 year and 1.9% at 2 years. The annual rebleeding
rate was 1.87%/person/year. The improvement in AChA-PCoA extension was observed
in 75 of 107 operated hemispheres (70.1%), which was higher than that in 7 of 105
unoperated hemispheres (35.2%). CONCLUSIONS: Revascularization may provide a
benefit over conservative therapy for hemorrhagic MMD patients. The improvement
of dilation and branch extension of AChA-PCoA might be correlated with the low
rebleeding rate.
PMID- 25127416
TI - Practical surgical indicators to identify candidates for radical resection of
insulo-opercular gliomas.
AB - OBJECT: Maximum resection of gliomas with minimum surgical complications usually
leads to optimum outcomes for patients. Radical resection of insulo-opercular
gliomas is still challenging, and selection of ideal patients can reduce risk and
obtain better outcomes. METHODS: This retrospective study included 83
consecutively treated patients with newly diagnosed gliomas located at the insulo
opercular region and extending to the sylvian fissure around the primary motor
and somatosensory cortices. The authors selected 4 characteristics as surgical
indicators: clear tumor boundaries, negative enhancement, intact lenticulostriate
arteries, and intact superior extremity of the central insular sulcus. RESULTS:
Univariate analysis showed that tumors with clear boundaries were associated with
higher rates of gross-total resection than were tumors with ambiguous boundaries
(75.7% vs 19.6%). Tumors with negative enhancement compared with enhanced tumors
were associated with lower frequency of tumor progression (32.0% vs 81.8%,
respectively) and lower rates of surgical complications (14.0% vs 45.5%,
respectively). Tumors with intact lenticulostriate arteries were associated with
higher rates of gross-total resection than were tumors with involved
lenticulostriate arteries (67.3% vs 11.8%, respectively). Tumors with intact
superior extremity of the central insular sulcus were associated with higher
rates of gross-total resection (57.4% vs 20.7%, respectively) and lower rates of
surgical complications (18.5% vs 41.4%, respectively) than were tumors with
involved anatomical structures. Multivariate analysis showed that clear tumor
boundaries were independently associated with gross-total resection (p < 0.001).
Negative enhancement was found to be independently associated with surgical
complications (p = 0.005), overall survival times (p < 0.001), and progression
free survival times (p = 0.004). Independent associations were also found between
intact lenticulostriate arteries and gross-total resection (p < 0.001), between
intact lenticulostriate arteries and progression-free survival times (p = 0.026),
and between intact superior extremity of the central insular sulcus and gross
total resection (p = 0.043). Among patients in whom all 4 indicators were
present, prognosis was good (5-year survival rate 93.3%), resection rate was
maximal (gross-total resection 100%), and surgical complication rate was minimal
(6.7%). Also among these patients, overall rates of survival (p = 0.003) and
progression-free survival (p = 0.005) were significantly higher than among
patients in whom fewer indicators were present. CONCLUSIONS: The authors propose
4 simple indicators that can be used to identify ideal candidates for radical
resection of insulo-opercular gliomas, improve the outcomes, and promote maximum
resection without introducing neurological complications. The indicators are
clear tumor boundaries, negative enhancement, intact lenticulostriate arteries,
and intact superior extremity of the central insular sulcus.
PMID- 25127417
TI - National socioeconomic indicators are associated with outcomes after aneurysmal
subarachnoid hemorrhage: a hierarchical mixed-effects analysis.
AB - OBJECT: Although heterogeneity exists in patient outcomes following subarachnoid
hemorrhage (SAH) across different centers and countries, it is unclear which
factors contribute to such disparities. In this study, the authors performed a
post hoc analysis of a large international database to evaluate the association
between a country's socioeconomic indicators and patient outcome following
aneurysmal SAH. METHODS: An analysis was performed on a database of 3552 patients
enrolled in studies of tirilazad mesylate for aneurysmal SAH from 1991 to 1997,
which included 162 neurosurgical centers in North and Central America, Australia,
Europe, and Africa. Two primary outcomes were assessed at 3 months after SAH:
mortality and Glasgow Outcome Scale (GOS) score. The association between these
outcomes, nation-level socioeconomic indicators (percapita gross domestic product
[GDP], population-to-neurosurgeon ratio, and health care funding model), and
patientlevel covariates were assessed using a hierarchical mixed-effects logistic
regression analysis. RESULTS: Multiple previously identified patient-level
covariates were significantly associated with increased mortality and worse
neurological outcome, including age, intraventricular hemorrhage, and initial
neurological grade. Among national-level covariates, higher per-capita GDP (p <
0.05) was associated with both reduced mortality and improved neurological
outcome. A higher population-to-neurosurgeon ratio (p < 0.01), as well as fewer
neurosurgical centers per population (p < 0.001), was also associated with better
neurological outcome (p < 0.01). Health care funding model was not a significant
predictor of either primary outcome. CONCLUSIONS: Higher per-capita gross GDP and
population-to-neurosurgeon ratio were associated with improved outcome after
aneurysmal SAH. The former result may speak to the availability of resources,
while the latter may be a reflection of better outcomes with centralized care.
Although patient clinical and radiographic phenotypes remain the primary
predictors of outcome, this study shows that national socioeconomic disparities
also explain heterogeneity in outcomes following SAH.
PMID- 25127418
TI - Monkey-adapted HIV-1 highlights in vivo significance of restriction factors.
AB - HIV-1 was isolated 31 years ago, yet models for studying HIV-1 pathogenesis in
vivo are still lacking. Recent experiments using an HIV-1 strain engineered to
replicate in macaques recapitulate several important features of human AIDS, and
provide insight into the genetics of cross-species transmission and emergence of
pathogenic retroviruses.
PMID- 25127420
TI - Catalytic olefin hydroamination with aminium radical cations: a photoredox method
for direct C-N bond formation.
AB - While olefin amination with aminium radical cations is a classical method for C-N
bond formation, catalytic variants that utilize simple 2 degrees amine
precursors remain largely undeveloped. Herein we report a new visible-light
photoredox protocol for the intramolecular anti-Markovnikov hydroamination of
aryl olefins that proceeds through catalytically generated aminium radical
intermediates. Mechanistic studies are consistent with a process involving amine
oxidation via electron transfer, turnover-limiting C-N bond formation, and a
second electron transfer step to reduce a carbon-centered radical, rendering the
overall process redox-neutral. A range of structurally diverse N-aryl
heterocycles can be prepared in good to excellent yields under conditions
significantly milder than those required by conventional aminium-based protocols.
PMID- 25127421
TI - The Importance of Sleep: Attentional Problems in School-Aged Children With Down
Syndrome and Williams Syndrome.
AB - In typically developing (TD) children, sleep problems have been associated with
day-time attentional difficulties. Children with developmental disabilities often
suffer with sleep and attention problems, yet their relationship is poorly
understood. The present study investigated this association in school-aged
children with Down syndrome (DS) and Williams syndrome (WS). Actigraphy and pulse
oximetry assessed sleep and sleep-disordered breathing respectively, and
attention was tested using a novel visual Continuous Performance Task
(CPT).Attentional deficits were evident in both disorder groups. In the TD group,
higher scores on the CPT were related to better sleep quality, higher
oxyhemoglobin saturation (SpO2), and fewer desaturation events. Sleep quality,
duration, and SpO2 variables were not related to CPT performance for children
with DS and WS.
PMID- 25127422
TI - Oxidative coupling of terminal alkyne with alpha-hydroxy ketone: an expedient
approach toward ynediones.
AB - An efficient and mild copper-catalyzed one-pot approach toward ynediones has been
established. A variety of ynediones were constructed directly through oxidative
coupling of alkyne with alpha-hydroxy ketone. Oxygen-oxidizing and neutral
conditions in one-pot for a wide range of substrates including natural product
derivatives make this transformation highly efficient and practical. On the basis
of control experiments, in situ IR measurements, and isotopic labeling
experiments, a plausible mechanism involving intermediate phenylglyoxal was
drawn. Applications by synthesis of various heterocycles were also investigated.
PMID- 25127419
TI - Characterizing solution surface loop conformational flexibility of the GM2
activator protein.
AB - GM2AP has a beta-cup topology with numerous X-ray structures showing multiple
conformations for some of the surface loops, revealing conformational flexibility
that may be related to function, where function is defined as either membrane
binding associated with ligand binding and extraction or interaction with other
proteins. Here, site-directed spin labeling (SDSL) electron paramagnetic
resonance (EPR) spectroscopy and molecular dynamic (MD) simulations are used to
characterize the mobility and conformational flexibility of various structural
regions of GM2AP. A series of 10 single cysteine amino acid substitutions were
generated, and the constructs were chemically modified with the
methanethiosulfonate spin label. Continuous wave (CW) EPR line shapes were
obtained and subsequently simulated using the microscopic order macroscopic
disorder (MOMD) program. Line shapes for sites that have multiple conformations
in the X-ray structures required two spectral components, whereas spectra of the
remaining sites were adequately fit with single-component parameters. For spin
labeled sites L126C and I66C, spectra were acquired as a function of temperature,
and simulations provided for the determination of thermodynamic parameters
associated with conformational change. Binding to GM2 ligand did not alter the
conformational flexibility of the loops, as evaluated by EPR and NMR
spectroscopies. These results confirm that the conformational flexibility
observed in the surface loops of GM2AP crystals is present in solution and that
the exchange is slow on the EPR time scale (>ns). Furthermore, MD simulation
results are presented and agree well with the conformational heterogeneity
revealed by SDSL.
PMID- 25127423
TI - Virulence attributes in Brazilian clinical isolates of Pseudomonas aeruginosa.
AB - Pseudomonas aeruginosa is an opportunistic human pathogen responsible for causing
a huge variety of acute and chronic infections with significant levels of
morbidity and mortality. Its success as a pathogen comes from its
genetic/metabolic plasticity, intrinsic/acquired antimicrobial resistance,
capacity to form biofilm and expression of numerous virulence factors. Herein, we
have analyzed the genetic variability, antimicrobial susceptibility as well as
the production of metallo-beta-lactamases (MBLs) and virulence attributes
(elastase, pyocyanin and biofilm) in 96 strains of P. aeruginosa isolated from
different anatomical sites of patients attended at Brazilian hospitals. Our
results revealed a great genetic variability, in which 86 distinct RAPD types
(89.6% of polymorphisms) were detected. Regarding the susceptibility profile, 48
strains (50%) were resistant to the antimicrobials, as follows: 22.92% to the
three tested antibiotics, 12.5% to both imipenem and meropenem, 11.46% to
ceftazidime only, 2.08% to imipenem only and 1.04% to both ceftazidime and
meropenem. Out of the 34 clinical strains of P. aeruginosa resistant to both
imipenem and meropenem, 25 (73.53%) were MBL producers by phenotypic method while
12 (35.29%) were PCR positive for the MBL gene SPM-1. All P. aeruginosa strains
produced pyocyanin, elastase and biofilm, although in different levels. Some
associations were demonstrated among the susceptibility and/or production of
these virulence traits with the anatomical site of strain isolation. For
instance, almost all strains isolated from urine (85.71%) were resistant to the
three antibiotics, while the vast majority of strains isolated from rectum (95%)
and mouth (66.67%) were susceptible to all tested antibiotics. Urine isolates
produced the highest pyocyanin concentration (20.15+/-5.65 MUg/ml), while strains
isolated from pleural secretion and mouth produced elevated elastase activity
(1441.43+/-303.08 FAU) and biofilm formation (OD590 0.676+/-0.32), respectively.
Also, MBL-positive strains produced robust biofilm compared to MBL-negative
strains. Collectively, the production of site-dependent virulence factors can be
highlighted as potential therapeutic targets for the treatment of infections
caused by heterogeneous and resistant strains of P. aeruginosa.
PMID- 25127424
TI - Matrix-assisted laser desorption ionization-time of flight mass spectrometry
assigns Escherichia coli to the phylogroups A, B1, B2 and D.
AB - Escherichia coli classification into phylogroups reflects the diversity of their
pathogenicity and their ecological niche, B2 isolates being the most virulent
among extra-intestinal strains. MALDI-TOF MS allows a quick, automated, simple
and inexpensive bacterial identification. We evaluated the MALDI-TOF MS as a tool
for E. coli phylogroup differentiation. We used 656 E. coli isolates, previously
assigned to phylogroup A, B1, B2, and D by multiplex PCR, to constitute
independent training and validation sets. We then defined two phylogrouping
strategies, both validated on spectra obtained by the 'direct transfer method'.
The first strategy used the MALDI Biotyper software (Bruker Daltonik) that
identified a single peak shift between isolates of phylogroup B2 and those of
groups A, B1 and D. It accurately classified 89% of the isolates. The second
strategy used the ClinProTools software (Bruker Daltonik) and was based on three
successive models. The model 1 adequately differentiated 92% of phylogroup B2
isolates from those belonging to phylogroups A, B1, D. The model 2 adequately
discriminated 87% of phylogroup D-isolates from those of phylogroups A and B1.
The model 3 correctly sorted 69% of A and B1-isolates. We concluded that clinical
laboratories could routinely and very quickly assign E. coli isolates to
phylogroups with MALDI-TOF MS. These methods could (i) expedite the detection of
the most virulent strains belonging to phylogroup B2 and (ii) be a first-line
tool to monitor the epidemiology of extra-intestinal pathogenic E. coli.
PMID- 25127425
TI - New insights into highly efficient reduction of CO2 to formic acid by using zinc
under mild hydrothermal conditions: a joint experimental and theoretical study.
AB - We report here a theoretical study with quantum chemical calculations based on
experimental results to understand highly efficient reduction of CO2 to formic
acid by using zinc under hydrothermal conditions. Results showed that zinc
hydride (Zn-H) is a key intermediate species in the reduction of CO2 to formic
acid, which demonstrates that the formation of formic acid is through an SN2-like
mechanism.
PMID- 25127427
TI - Advances in understanding the mechanism of zebrafish heart regeneration.
AB - The adult mammalian heart was once believed to be a post-mitotic organ without
any capacity for regeneration, but recent findings have challenged this dogma. A
modified view assigns the mammalian heart a measurable capacity for regeneration
throughout its lifetime, with the implication that endogenous regenerative
capacity can be therapeutically stimulated in the injury setting. Although
extremely limited in adult mammals, the natural capacity for organ regeneration
is a conserved trait in certain vertebrates. Urodele amphibians and teleosts are
well-known examples of such animals that can efficiently regenerate various
organs including the heart as adults. By understanding how these animals
regenerate a damaged heart, one might obtain valuable insights into how
regeneration can be augmented in injured human hearts. Among the regenerative
vertebrate models, the teleost zebrafish, Danio rerio, is arguably the best
characterized with respect to cardiac regenerative responses. Knowledge is still
limited, but a decade of research in this model has led to results that may help
to understand how cardiac regeneration is naturally stimulated and maintained.
This review surveys recent advances in the field and discusses current
understanding of the endogenous mechanisms of cardiac regeneration in zebrafish.
PMID- 25127429
TI - Spinal dural arteriovenous fistula: correlation between radiological and clinical
findings.
AB - OBJECT: The pathophysiology of spinal dural arteriovenous fistulas (SDAVFs)
results in perimedullary venous congestion and in turn central cord congestion.
Clinically, this presents with progressive neurological dysfunctions that, if
diagnosed in a timely fashion, can be at least halted and in part reversed. In
SDAVFs, imaging features on MRI and digital subtraction angiography (DSA) have
not been studied in conjunction with clinical findings. The primary purpose of
the present study was to test if severity of clinical presentation varies in
relation to imaging. METHODS: This retrospective cohort study identified 12
patients treated for SDAVF at the authors' institution. The extent of venous
congestion and cord edema was quantified by the number of vertebral levels shown
to be affected on DSA and MRI. A modified Aminoff-Logue Scale (ALS) score was
assigned at the time of diagnosis and again after definitive therapy. The
patients were divided into one of two groups: those with venous congestion < 7
and >= 7 vertebral levels seen on DSA and MRI and with central cord edema < 6 and
>= 6 levels. A t-test was used to assess for a difference in the presenting ALS
score between the groups. RESULTS: Patients with >= 7 levels of venous congestion
reported greater functional disability (DSA: p <= 0.001, Cohen's d = 0.509; and
MRI: p <= 0.001, d = 0.632). Patients with a greater extent of cord edema also
reported worse functional disability (p <= 0.001, d = 2.31). There was a strong
linear correlation between the post- and pretreatment ALS scores (R(2) = 0.86)
for those with successful interventions (n = 9). CONCLUSIONS: In patients with an
SDAVF, the severity of the neurological dysfunction may be predicted by the
extent of DSA- and MRI-documented venous congestion and cord edema. There was a
strong positive relationship between initial and posttreatment neurological
dysfunction.
PMID- 25127430
TI - Long-term patient outcomes after posterior cervical foraminotomy: an analysis of
151 cases.
AB - OBJECT: The authors conducted a study to investigate the rate and timing of
reoperation due to symptom recurrence after unilateral posterior cervical
foraminotomy (PCF). METHODS: The authors retrospectively reviewed demographic,
surgical, and clinical data from 151 patients who underwent unilateral PCF at
their institution with an average follow-up of 4.15 years. The main outcome
variables were reoperation rate, time to reoperation, and short- and long-term
radiculopathy improvement rates. Kaplan-Meier analyses were conducted to assess
risk of reoperation and recurrence of radiculopathy over time. RESULTS: After
index PCF in 151 patients, the overall reoperation rate was 9.9% (15 patients).
The average time until reoperation was 2.4 years, and the average last follow-up
examination was 4.15 years after the first surgery. Patients who presented with
preoperative neck pain in addition to radiculopathy had a higher risk for
reoperation and a shorter time to reoperation. The majority of patients who
underwent a reoperation had an anterior cervical discectomy and fusion (80%). A
smaller number of patients had reoperation that included a repeat PCF (6.7%) or
laminectomy with posterior cervical fusion (13.3%). The rate of same-level
reoperation (6.6%, 10 patients) was significantly higher (p = 0.05) when compared
with adjacent-segment (1.3%, 2 patients) or distant-segment (1.9%, 3 patients)
reoperation. At last follow-up, the overall rate of improvement in radiculopathy
was 85%, with the majority of patients (91.4%) experiencing resolution as early
as 1 month after index surgery. Following the subgroup that experienced initial
symptom improvement, 16.1% of these patients experienced radiculopathy recurrence
an average of 7.3 years after the initial operation. While the reoperation rate
for the overall cohort in this series was 9.9%, patients with follow-up periods
longer than 2 years had a reoperation rate of 18.3%. Moreover, patients with more
than 10 years of follow-up had a reoperation rate of 24.3%. CONCLUSIONS: PCF is a
procedure performed to address nerve root compression in the cervical spine. The
authors evaluated 151 patients who underwent unilateral PCF and found a
reoperation rate of 9.9% at an average of 2.4 years after the initial surgery
(6.6% at same level, 3.3% elsewhere). The reoperation rates reached 18.3% and
24.3% in patients with follow-up periods longer than 2 and 10 years,
respectively. The authors' analysis revealed that patients with no preoperative
neck pain had the lowest rates of revision surgery after PCF.
PMID- 25127426
TI - 2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and
management: The Joint Task Force on non-cardiac surgery: cardiovascular
assessment and management of the European Society of Cardiology (ESC) and the
European Society of Anaesthesiology (ESA).
PMID- 25127431
TI - Computed tomography-guided epidural patching of postoperative cerebrospinal fluid
leaks.
AB - OBJECT: Cerebrospinal fluid leaks due to unrecognized durotomy during spinal
surgery are often managed with a second surgery for dural closure. CT-guided
percutaneous patching targeted to the dural defect offers an alternative to
surgery since it can be performed in a minimally invasive fashion without the
need for general anesthesia. This case series describes the authors' experience
using targeted CT-guided percutaneous patching to repair incidental durotomies
incurred during spinal surgery. METHODS: This investigation is a retrospective
case series involving patients who underwent CT-guided percutaneous patching of
surgical incidental durotomies and were referred between January 2007 and June
2013. Their presenting clinical history, myelographic findings, and clinical
outcomes, including the need for eventual surgical duraplasty, were reviewed.
RESULTS: Nine cases were identified, including 7 durotomies incurred during
lumbar discectomy, one due to a medial transpedicular screw breach, and one
incurred during vertebrectomy for spinal osteosarcoma. All patients who had
favorable outcomes with percutaneous intervention alone had 2 common features:
dural defect of 4 mm or smaller and absence of a pseudomeningocele. Patients with
CSF leaks complicated by pseudomeningocele and those with a dural defect of 6 mm
or more all required eventual surgical management. CONCLUSIONS: The authors'
results suggest that findings on CT myelography may help predict which patients
with postsurgical durotomy can be treated with percutaneous intervention. In
particular, CT-guided patching may be more likely to be successful in those
patients with dural defects of less than 5 mm and without pseudomeningocele. In
patients with larger dural defects or pseudomeningoceles, percutaneous blood
patching alone is unlikely to be successful.
PMID- 25127432
TI - Utility of routine biopsy at vertebroplasty in the management of vertebral
compression fractures: a tertiary center experience.
AB - OBJECT: The authors assess the utility of routine biopsy at vertebroplasty for
vertebral compression fracture (VCF) as a tool in the early detection of
malignancy in presumed benign VCF. METHODS: A prospective observational study was
conducted on a cohort of consecutive patients undergoing vertebroplasty over a 5
year period between April 2006 and March 2011 at the Royal London Hospital.
Polymethylmethacrylate cement injection was used in every procedure.
Intraoperative vertebral body biopsy was performed routinely at every level of
VCF. Pain visual analog scale (VAS) scores, Oswestry Disability Index (ODI)
scores, analgesic usage, and complications were recorded preoperatively and at 1
day, 1 week, 1 month, 6 months, and 1 year postoperatively. RESULTS: A total of
202 levels were augmented in 147 patients. The most common levels augmented were
T-12 (17%), L-1 (18%), and L-4 (10%). Analysis of 184 routine vertebral biopsies
in 135 patients revealed that in 86 patients with presumed osteoporosis and no
prior cancer diagnosis, 4 (4.7%) had a malignant VCF. In 20 known cancer patients
presumed to be in remission, 2 (10%) had a malignant VCF. Routine vertebral
biopsy returned an overall cancer diagnosis rate of 5.5% (6 of 109) when
combining the 2 groups (patients with no prior history of cancer or cancer
thought to be in remission). In these 6 patients, history, examination,
laboratory tests, and preprocedure imaging all failed to suggest malignancy
diagnosed at routine biopsy. Significant reductions in pain VAS and ODI scores
were evident at Day 1 and were sustained at up to 1 year postoperatively (p <
0.001). They were not dependent on the level of fracture (T3-10, T11-L2, or L3
S1) (p > 0.05), number of levels treated (single level, 2 levels, or > 2 levels)
(p > 0.05), or etiology of VCF (p > 0.05). The complication rate was 6% (9 of
147). There were 5 deaths, none of which were directly related to surgery.
CONCLUSIONS: Routine vertebral biopsy performed at vertebroplasty may demonstrate
cancer-related VCFs in unsuspected patients with no previous cancer diagnosis or
active malignancy in patients previously thought to be in remission. This early
diagnosis of cancer or relapsed disease will play an important role in expediting
patients' subsequent cancer management. In cases of multiple-level VCF, the
authors advocate biopsy at each level to maximize the diagnostic yield from the
specimens and to avoid missing a malignancy at a single level.
PMID- 25127433
TI - Progression of ossification of the posterior longitudinal ligament of the
thoracic spine following posterior decompression and stabilization.
AB - OBJECT: Despite its potential clinical impact, information regarding progression
of thoracic ossification of the posterior longitudinal ligament (OPLL) is scarce.
Posterior decompression with stabilization is currently the primary surgical
treatment for symptomatic thoracic OPLL; however, it remains unclear whether
thoracic OPLL increases in size following spinal stabilization. It is also
unknown whether patients' clinical symptoms worsen as OPLL size increases. In
this retrospective case series study, the authors examined the postoperative
progression of thoracic OPLL. METHODS: Nine consecutive patients with thoracic
OPLL who underwent posterior decompression and fixation with a minimum follow-up
of 3 years were included in this study. Thin-slice CT scans of the thoracic spine
obtained at the time of surgery and the most recent follow-up were analyzed. The
level of the most obvious protrusion of ossification was determined using the
sagittal reconstructions, and the ossified area was measured on the axial
reconstructed scan at the level of the most obvious protrusion of ossification
using the DICOM (digital imaging and communications in medicine) software
program. Myelopathy severity was assessed according to the Japanese Orthopaedic
Association (JOA) scale score for lower-limb motor function on admission, at
postoperative discharge, and at the last follow-up visit. RESULTS: The OPLL area
was increased in all patients. The mean area of ossification increased from 83.6
+/- 25.3 mm(2) at the time of surgery to 114.8 +/- 32.4 mm(2) at the last follow
up visit. No patients exhibited any neurological deterioration due to OPLL
progression. CONCLUSIONS: The present study demonstrated that the size of the
thoracic OPLL increased after spinal stabilization. Despite diminished local
spinal motion, OPLL progression did not decrease or stop. Physicians should pay
attention to ossification progression in patients with thoracic OPLL.
PMID- 25127434
TI - Targeted structure modulation of "pillar-layered" metal-organic frameworks for
CO2 capture.
AB - Two new zinc MOFs with similar "pillar-layered" framework structures based on
1,1'-biphenyl-2,2',6,6'-tetracarboxylic acid (H4bpta) and two different
bipyridine pillar ligands, namely {[Zn4(bpta)2(4-pna)2(H2O)2].4DMF.3H2O}n (1) and
{[Zn2(bpta)(bpy-ea)(H2O)].2DMF.H2O}n (2) (4-pna = N-(4-pyridyl)isonicotinamide
and bpy-ea = 1,2-bis(4-pyridyl)ethane), have been synthesized and investigated
with their CO2 adsorption properties. By analysis of the structure properties and
the CO2 adsorption performances of these two MOFs, it was found that the
introduction of polar acylamide groups via 4-pna resulted in 1 with enhanced CO2
capacity and CO2/CH4 selectivity at low pressure. In contrast, the framework of 2
shows flexible properties originating from the flexibility of the ethanediylidene
group in the bpy-ea ligand, which benefits the sieve effect of pores to give
higher CO2/CH4 selectivity at a relatively high pressure range.
PMID- 25127435
TI - The role of serum soluble urokinase-type plasminogen activator receptor in stable
chronic obstructive pulmonary disease.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) results from an abnormal
inflammatory response of the lungs to noxious particles or gases. Serum soluble
urokinase-type plasminogen activator receptor (suPAR) is a glycoprotein secreted
during infections and inflammation. The main goal of this study was to evaluate
the serum suPAR level in stable COPD patients compared with a control group.
METHODS: Forty-six stable COPD patients and 41 control subjects were included in
the study. Blood samples were collected from 46 stable COPD patients (40 men, 6
women; mean [SD] age, 55.92 [7.91] years; the forced expiratory volume in 1
second, 45.32% [19.1%] of predicted). Forty-one healthy subjects were selected as
control subjects and were matched to COPD patients with respect to age and body
mass index. Serum suPAR and plasma fibrinogen levels were measured in stable COPD
patients and control subjects. RESULTS: Serum suPAR levels of the COPD patients
were significantly higher than those of the control subjects (4.94 [2.79] and
2.40 [2.01] ng/mL, respectively; P < 0.001). Plasma fibrinogen levels of the COPD
patients were significantly higher than those of the control subjects (406.77
[172.6] and 336.53 [96.1] g/L, respectively; P < 0.05). CONCLUSIONS: Our study
indicated that serum suPAR may play an important role in the inflammatory process
of COPD, and this increase may be particularly large for patients in Global
Initiative for Chronic Obstructive Lung Disease stages III and IV. Serum suPAR
and plasma fibrinogen level measurements may be useful for the evaluation of
stable COPD.
PMID- 25127436
TI - Little adjustments significantly improve the Turkevich synthesis of gold
nanoparticles.
AB - In this report, we show how the classical and widely used Turkevich synthesis can
be improved significantly by simple adjustments. The gold nanoparticles (AuNPs)
produced with the optimized protocol have a much narrower size distribution (5-8%
standard deviation), and their diameters can be reproduced with unrivaled little
variation (<3%). Moreover, large volumes of these particles can be produced in
one synthesis; we routinely synthesize 1000 mL of ~3.5 nM AuNPs. The key features
of the improved protocol are the control of the pH by using a citrate buffer
instead of a citrate solution as the reducing agent or stabilizer and optimized
mixing of reagents. Further, the shape uniformity of the particles can be
improved by addition of 0.02 mM EDTA. While the proposed protocol is as
straightforward as the original Turkevich protocol, it is more tolerant against
variations in precursor concentration.
PMID- 25127438
TI - Spinal cord--skeletal muscle cocultures detect muscle-relaxant action of
botulinum neurotoxin A.
AB - The mouse LD50 assay is routinely used for potency testing of botulinum toxins.
Unfortunately, this test is associated with severe pain and distress in animals
and requires large quantities of mice. Here we used cocultures of spinal cord and
muscle tissue as an alternative for probing botulinum toxins. Cocultures were
prepared from mouse embryonic tissue (C57/BL6J) and cultured for 24-27 days. In
these cultures spontaneous muscle activity was quantified in sham- and botulinum
toxin-treated cultures for up to 3 days by video microscopy. At a concentration
of 58 fmol/L or higher, incobotulinumtoxin A significantly reduced the frequency
of muscle contractions within 24 hours after incubation. Hence, nerve-muscle
cultures are similar sensitive as the mouse LD50 assay. The limit of detection,
as observed in our study, is close to the most sensitive cell-based bioassays,
capable to detect concentrations of botulinum neurotoxin A between 30 and 50
fmol/L. However, spontaneous muscle activity of individual cultures displayed
considerable fluctuations when evaluated on a day-to-day basis. Generally, the
authors would like to emphasize, that in its present form, this in vitro assay
might be too laborious for botulinum toxin potency testing. Thus, methodical
improvements to decrease data variability are the next milestone to be passed
towards developing this model into an assay that can be utilized for reducing
animal experimentation.
PMID- 25127437
TI - Incense use and cardiovascular mortality among Chinese in Singapore: the
Singapore Chinese Health Study.
AB - BACKGROUND: Incense burning is common in many parts of the world. Although it is
perceived that particulate matter from incense smoke is deleterious to health,
there is no epidemiologic evidence linking domestic exposure to cardiovascular
mortality. OBJECTIVE: We examined the association between exposure to incense
burning and cardiovascular mortality in the Singapore Chinese Health Study.
METHODS: We enrolled a total of 63,257 Singapore Chinese 45-74 years of age
during 1993-1998. All participants were interviewed in person to collect
information about lifestyle behaviors, including the practice of burning incense
at home. We identified cardiovascular deaths via record linkage with the
nationwide death registry through 31 December 2011. RESULTS: In this cohort,
76.9% were current incense users, and most of the current users (89.9%) had
burned incense daily for >= 20 years. Relative to noncurrent users, current users
had a 12% higher risk of cardiovascular mortality [multivariable adjusted hazard
ratio (HR) = 1.12; 95% CI: 1.04, 1.20]. The HR was 1.19 (95% CI: 1.03, 1.37) for
mortality due to stroke and 1.10 (95% CI: 1.00, 1.21) for mortality due to
coronary heart disease. The association between current incense use and
cardiovascular mortality appeared to be limited to participants without a history
of cardiovascular disease at baseline (HR = 1.16; 95% CI: 1.07, 1.26) but not
linked to those with a history (HR = 1.00; 95% CI: 0.86, 1.17). In addition, the
association was stronger in never-smokers (HR = 1.12; 95% CI: 1.02, 1.23) and
former smokers (HR = 1.19; 95% CI: 1.00, 1.42) than in current smokers (HR =
1.05; 95% CI: 0.91, 1.22). CONCLUSIONS: Long-term exposure to incense burning in
the home environment was associated with an increased risk of cardiovascular
mortality in the study population.
PMID- 25127439
TI - Laparoscopic sleeve gastrectomy in morbidly obese patients with end-stage heart
failure and left ventricular assist device: medium-term results.
AB - BACKGROUND: Morbid obesity precludes patients with end-stage heart failure from
becoming cardiac transplant candidates. This study evaluates the safety and
efficacy of laparoscopic sleeve gastrectomy (LSG) as a means to transplant
candidacy in such patients. METHODS: Morbidly obese patients with end-stage heart
failure, who were ineligible for cardiac transplantation and underwent LSG
between 2008 and 2013, were reviewed retrospectively. Demographic
characteristics, perioperative details, percentage of excess weight loss (%EWL),
and status of transplant candidacy were analyzed. RESULTS: Six patients (3 men)
with end-stage heart failure and morbid obesity underwent LSG. Three patients
(50%) had a left ventricular assist device (LVAD) in place at the time of
surgery. Median age was 34 (31-66) years and mean preoperative body mass index
(BMI) was 47.6+/-3.0 kg/m2. Median operative time was 90 (66-141) minutes, with a
median length of stay of 7 (4-16) days. There were no perioperative deaths. One
patient suffered a spontaneous flank hematoma. The same patient also had
thrombosis of the LVAD pump at 3 weeks postoperatively, requiring an uneventful
device exchange. At median follow-up of 22 (12-70) months, the mean %EWL was
51.4+/-10.3% with a decrease in BMI to 34.3+/-2.4 kg/m2 (P<.05). All patients had
lost sufficient weight to become transplant eligible within 12 months of surgery.
Two patients had undergone successful transplantation and another 2 were on the
transplant list. CONCLUSION: LSG appears to be a safe, technically feasible, and
effective method for obtaining adequate weight loss in morbidly obese patients
with end-stage heart failure and mechanical circulatory support, subsequently
improving their access to cardiac transplantation. This is the largest case
series to date of this high-risk group of patients undergoing LSG.
PMID- 25127440
TI - Correlation of impaired subjective visual vertical and postural instability in
Parkinson's disease.
AB - Perception of verticality is essential for postural control. On the other hand,
postural instability is one of the cardinal features in Parkinson's disease (PD).
Thus, the objective of this study was to evaluate the vertical perception using
the subjective visual vertical test in PD patients with different degrees of
postural instability and in different stages of disease. Forty five idiopathic PD
patients were evaluated using the Unified Parkinson's Disease Rating Scale
(UPDRS), the Hoehn and Yahr Scale, the clinical test for postural instability,
and the subjective visual vertical test. Forty-five healthy individuals were
evaluated in the control group. PD patients had a compromised perception of
verticality and a disturbed processing of graviceptive pathways. Good correlation
was also found between subjective visual vertical and postural instability.
Patients with the worst postural instability had greater deviations of subjective
visual vertical. There was also a positive correlation between subjective visual
vertical and scores on the UPDRS and Hoehn and Yahr Scale, with good and
reasonable degree of intensity, respectively. These findings suggest that the
perception of verticality is affected in PD patients and this abnormal vertical
perception and disturbed processing of graviceptive pathways are associated with
postural instability and to a lesser degree with disease severity.
PMID- 25127441
TI - Dementia is associated with iron-deficiency anemia in females: a population-based
study.
AB - Cognitive derangement and neurological symptoms are observed in patients with
anemia. Although it is still controversial, a few studies suggested that anemia
may increase the risk of dementia. This study aimed to explore the association
between iron-deficiency anemia (IDA) and dementia in a population-based case
control study. We retrieved our study sample from the Taiwan Longitudinal Health
Insurance Database 2000. We extracted 8300 subjects with a diagnosis of dementia
and 8300 age- and gender-matched controls. The results showed that there was a
significant difference in the prevalence of prior IDA between cases and controls
(6.0% vs. 3.8%, p<0.001). The conditional logistic regression analysis suggested
that the odds ratio (OR) of prior IDA for cases was 1.36 (95% CI: 1.07-1.74)
compared to controls after adjusting for subjects' monthly income, geographic
location, urbanization level, hyperlipidemia, diabetes, hypertension, and alcohol
abuse. Among female subjects, the adjusted OR of prior IDA for cases was as high
as 2.00 (95% CI: 1.42-2.80) compared to controls. However, in men-no increased
odds of prior IDA were observed, compared to controls. We concluded that women
with dementia had a higher prevalence of prior IDA, compared to controls.
PMID- 25127442
TI - Quality of life after total and subtotal gastrectomy for gastric carcinoma.
AB - BACKGROUND: There remains debate as to whether quality of life (QoL) is better
for patients following sub-total gastrectomy (SG) or total gastrectomy (TG) for
cancer. Both have similar survival rates provided an R0 resection is performed
and in many series the morbidity and mortality after TG is higher than SG. The
aim of this study was to evaluate the QoL in patients after TG and SG for cancer.
METHOD: All surviving patients who had undergone TG or SG between 1994 and 2009
were identified from a prospectively collected database and sent the European
Organisation for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ
C30 v.3) and the gastric module (QLQ-STO22). RESULTS: From a total of 261
patients who had undergone TG or SG in the study period, 91 were still alive and
53 responded. There was no significant difference between the QoL between TG and
SG based on functional scales and global health status. However dysphagia and
eating restrictions were significantly worse in the TG group. CONCLUSION: This
study has demonstrated that there is no difference in overall QoL in patients
with TG or SG although eating restrictions and dysphagia are worse after TG.
PMID- 25127443
TI - Effects of different types of N deposition on the fungal decomposition activities
of temperate forest soils.
AB - Nitrogen (N) deposition significantly affects soil microbial activities and
litter decomposition processes in forest ecosystems. However, the changes in soil
fungi during litter decomposition remain unclear. In this study, ammonium nitrate
was selected as inorganic N (IN), whereas urea and glycine were selected as
organic N (ON). N fertilizer with different IN-to-ON ratios (1:4, 2:3, 3:2, 4:1,
and 5:0) was mixed in equal amounts and then added to temperate forest soils.
Half of each treatment was simultaneously added with streptomycin to inhibit soil
bacteria. The activities of enzymes involved in litter decomposition (invertase,
beta-glucosidase, cellulase, polyphenol oxidase, and phosphatase) were assayed
after a three-year field experiment. The results showed that enzymatic activities
were inhibited by IN addition but accelerated by ON addition in the non
antibiotic addition treatments. An increase in ON in the mixed N fertilizer also
shifted enzymatic activities from N inhibition to N stimulation. Similarly, in
the antibiotic addition treatments, fungal activities revealed the same trends,
but they were seriously inhibited by IN and significantly accelerated by ON.
These results indicated that soil fungi were more sensitive to N deposition,
particularly to ON. A large amount of ON may convert soil microbial communities
into a fungi-dominated system. However, excessive ON deposition (20% IN+80% ON)
caused N saturation and repressed fungal activities. These results suggested that
soil fungi were sensitive to N type and that different IN-to-ON ratios may induce
diverse ecological effects on soil fungi.
PMID- 25127444
TI - Socioeconomic development as a determinant of the levels of organochlorine
pesticides and PCBs in the inhabitants of Western and Central African countries.
AB - Several studies of environmental samples indicate that the levels of many
persistent organic pollutants (POPs) are increasing in Africa, but few studies
have been conducted in humans. Simultaneously, many African countries are
experiencing a rapid economic growth and implementing information and
communication technologies (ICT). These changes have generated high amounts of
electronic waste (e-waste) that have not been adequately managed. We tested the
hypothesis that the current levels of two main classes of POPs in Western and
Central African countries are affected by the degree of socioeconomic
development. We measured the levels of 36 POPs in the serum of recent immigrants
(N=575) who came from 19 Sub-Saharan countries to the Canary Islands (Spain). We
performed statistical analyses on their anthropometric and socioeconomic data.
High median levels of POPs were found in the overall sample, with differences
among the countries. Organochlorine pesticide (OCP) and polychlorinated biphenyl
(PCB) levels increased with age. People from low-income countries had
significantly higher OCP levels and much lower PCB levels than those from high
income countries. We found a significant association between the implementation
of ICT and PCB contamination. Immigrants from the countries with a high volume of
imports of second-hand electronic equipment had higher PCB levels. The economic
development of Africa and the e-waste generation have directly affected the
levels of POPs. The POP legacies of these African populations most likely are due
to the inappropriate management of the POPs' residues.
PMID- 25127445
TI - A nationwide survey and emission estimates of cyclic and linear siloxanes through
sludge from wastewater treatment plants in Korea.
AB - Siloxanes are widely used in various industrial applications as well as in
personal care products. Despite their widespread use and potential toxic effects,
few studies have reported on the occurrence of siloxanes in the environment. In
this study, we determined the concentrations of 5 cyclic and 15 linear siloxanes
in sludge collected from 40 representative wastewater treatment plants (WWTPs) in
Korea. Total concentrations of 20 siloxanes (Sigmasiloxane) in sludge ranged from
0.05 to 142 (mean: 45.7) MUg/g dry weight, similar to the concentrations reported
in European countries but higher than those reported in China. The concentrations
of siloxanes in sludge from domestic WWTPs were significantly (p<0.01) higher
than those from industrial WWTPs, indicating higher consumption of siloxanes in
various personal care products (e.g. shampoos and conditioners). The major
siloxane compounds found in sludge were decamethylcyclopentasilane (D5),
docosamethyldecasiloxane (L10) and dodecamethylcyclohexasilane (D6), which
collectively accounted for, on average, 62% of the Sigmasiloxane concentrations.
Non-parametric multidimensional scaling ordination of the profiles of siloxanes
indicated the existence of different usage patterns of siloxanes between
industrial and household activities. Multiple linear regression analysis of
siloxane concentrations and WWTP characteristics suggested that D5, D6 and linear
siloxane concentrations in sludge were positively correlated with population
served by a WWTP. Environmental emission fluxes of cyclic and linear siloxanes
through sludge disposal in Korea were 14,800 and 18,500 kg/year, respectively.
This is the first report describing occurrence and environmental emission of
siloxanes through sludge in Korea.
PMID- 25127447
TI - Solid mesostructured polymer-surfactant films at the air-liquid interface.
AB - Pioneering work by Edler et al. has spawned a new sub-set of mesostructured
materials. These are solid, self-supporting films comprising surfactant micelles
encased within polymer hydrogel; composite polymer-surfactant films can be grown
spontaneously at the air-liquid interface and have defined and controllable
mesostructures. Addition of siliconalkoxide to polymer-surfactant mixtures allows
for the growth of mesostructured hybrid polymer-surfactant silica films that
retain film geometry after calcinations and exhibit superior mechanical
properties to typically brittle inorganic films. Growing films at the air-liquid
interface provides a rapid and simple means to prepare ordered solid inorganic
films, and to date the only method for generating mesostructured films thick
enough (up to several hundred microns) to be removed from the interface.
Applications of these films could range from catalysis to encapsulation of
hydrophobic species and drug delivery. Film properties and mesostructures are
sensitive to surfactant structure, polymer properties and polymer-surfactant
phase behaviour: herein it will be shown how film mesostructure can be tailored
by directing these parameters, and some interesting analogies will be drawn with
more familiar mesostructured silica materials.
PMID- 25127446
TI - Investigation of organochlorine pesticides from the Indus Basin, Pakistan:
sources, air-soil exchange fluxes and risk assessment.
AB - Present study aimed to evaluate the contamination status of organochlorine
pesticides (OCPs) and their associated potential for air-soil exchange and health
risks from ecologically important sites of the Indus Basin, Pakistan. Among
different OCPs investigated, SigmaDDTs and SigmaHCHs were more prevalent
compounds in the agricultural soils and ambient air samples of the study area.
The average concentrations for DDTs were found higher at downstream agricultural
sites, particularly at Head Panjnad (Soil: 320 ng/g; Air: 743 pg/m(3)) and acting
as an ultimate sink of SigmaOCP burden in soils. Spatial distribution patterns
inferred ubiquitous distribution of SigmaDDTs in soils and air of the study area.
Source diagnostic ratios demonstrated that studied OCPs either are illegally
being used in agricultural practices or/and they are residues of past use in the
environment. Fugacity fraction model revealed wide variations (ff=0.12-0.94) with
20% of OCPs above equilibrium range and net volatilization of alpha-endosulfan,
beta-HCH and o,p'-DDD. Assessment of cancer risks for OCPs indicated a higher
cancer risk (CR>1*10(-6)) for the residents of the Indus Basin. According to the
available soil quality guidelines, DDTs and HCHs were above the permissible
limits and pose a threat to natural habitat and biodiversity of the Indus Basin.
PMID- 25127448
TI - Motor and memory function in rat models of cyanide toxicity and vascular
occlusion induced ischemic injury.
AB - Although oxidative stress is characteristic of global vascular occlusion and
cyanide toxicity, the pattern of cerebral metabolism reconditioning and rate of
progression or reversal of neural tissue damage differ for both forms of
ischemia. Thus, it is important to compare cognitive and motor functions in both
models of ischemia involving cyanide treatment (CN) and vascular occlusion (VO).
Adult Wistar rats (N=30) were divided into three groups; VO (n=12), CN (n=12) and
Control-CO (n=6). The CN was treated with 30mg/Kg of potassium cyanide (KCN); VO
was subjected to global vascular occlusion-both for duration of 10 days. The
control (CO) was fed on normal rat chow and water for the same duration. At day
10, the test and control groups (CN, VO and CO) were subjected to motor function
tests (Table edge tests and Open Field Test) and memory function tests (Y-Maze
and Novel object recognition) while the withdrawal groups CN-I and VO-I were
subjected to the same set of tests at day 20 (the withdrawal phase). The results
show that both cyanide toxicity and vascular occlusion caused a decline in motor
and memory function when compared with the control. Also, the cyanide treatment
produced a more rapid decline in these behavioral parameters when compared with
the vascular occlusion during the treatment phase. After the withdrawal phase,
cyanide treatment (CN-I) showed either an improvement or restoration of motor and
memory function when compared to the CN and control. Withdrawal of vascular
occlusion caused no improvement, and in some cases a decline in motor and memory
function. In conclusion, cyanide toxicity caused a decline in motor and memory
function after the treatment while vascular occlusion caused no significant
decline in cognition and motor function at this time. After the withdrawal phase,
the effect of cyanide toxicity was reduced and significant improvements were
observed in the behavioral tests (motor and cognitive), while a decline in these
functions were seen in the vascular occlusion group after this phase.
PMID- 25127450
TI - Production of destruxins from Metarhizium spp. fungi in artificial medium and in
endophytically colonized cowpea plants.
AB - Destruxins (DTXs) are cyclic depsipeptides produced by many Metarhizium isolates
that have long been assumed to contribute to virulence of these entomopathogenic
fungi. We evaluated the virulence of 20 Metarhizium isolates against insect
larvae and measured the concentration of DTXs A, B, and E produced by these same
isolates in submerged (shaken) cultures. Eight of the isolates (ARSEF 324, 724,
760, 1448, 1882, 1883, 3479, and 3918) did not produce DTXs A, B, or E during the
five days of submerged culture. DTXs were first detected in culture medium at 2-3
days in submerged culture. Galleria mellonella and Tenebrio molitor showed
considerable variation in their susceptibility to the Metarhizium isolates. The
concentration of DTXs produced in vitro did not correlate with percent or speed
of insect kill. We established endophytic associations of M. robertsii and M.
acridum isolates in Vigna unguiculata (cowpeas) and Cucumis sativus (cucumber)
plants. DTXs were detected in cowpeas colonized by M. robertsii ARSEF 2575 12
days after fungal inoculation, but DTXs were not detected in cucumber. This is
the first instance of DTXs detected in plants endophytically colonized by M.
robertsii. This finding has implications for new approaches to fungus-based
biological control of pest arthropods.
PMID- 25127451
TI - Productivity change of surgeons in an academic year.
AB - OBJECTIVE: The goal of this study was to calculate total factor productivity of
surgeons in an academic year and to evaluate the effect of surgical trainees on
their productivity. STUDY DESIGN: We analyzed all the surgical procedures
performed from April 1 through September 30, 2013 in the Teikyo University
Hospital. The nonradial and nonoriented Malmquist model under the variable
returns-to-scale assumptions was employed. A decision-making unit is defined as a
surgeon with the highest academic rank in the surgery. Inputs were defined as the
number of physicians who assisted in surgery, and the time of surgical operation
from skin incision to skin closure. The output was defined as the surgical fee
for each surgery. April is the beginning month of a new academic year in Japan,
and we divided the study period into April to June and July to September 2013. We
computed each surgeon's Malmquist index, efficiency change, and technical change.
RESULTS: We analyzed 2789 surgical procedures that were performed by 105
surgeons. The Malmquist index of all surgeons was significantly greater than 1 (p
= 0.0033). The technical change was significantly greater than 1 (p < 0.0001).
However, the efficiency change was not statistically significantly different from
1 (p = 0.1817). CONCLUSIONS: The surgeons are less productive in the beginning
months of a new academic year. The main factor of this productivity loss is
considered to be surgical training.
PMID- 25127452
TI - Development of a web-based laparoscopic technical skills assessment and testing
instrument: a pilot study.
AB - OBJECTIVE: Current surgical training programs rely heavily on subjective
assessments to measure operative proficiency, despite heavy emphasis on
standardized testing as a means to rank scholastic ability. A compact
laparoscopic simulator was developed with the intention to create a technical
skill evaluation system that resembles standardized testing to provide the user
with real-time percentile scores in a variety of skill metrics. The calculation
of percentiles is only accurate if the pool of scores resembles a specific
distribution (e.g., normal or log-normal distribution). We hypothesize that the
grading measures provided by the simulator will follow normal or log-normal
distributions. MATERIALS AND METHODS: A total of 29 surgical trainees with
varying levels of laparoscopic experience were surveyed regarding their current
training, proficiencies, and experience with the Fundamentals of Laparoscopic
Surgery curriculum and then asked to perform a standard peg-transfer task 5
times. A proprietary device placed along the trocars of a laparoscopic box
trainer was used to gather data that, when subjected to unique algorithms, gave
real-time, web-based feedback to trainees on the following metrics: volume of
instrument use, economy of movement, angular instrument path, instrument
rotation, bimanual coordination, smoothness, time to task completion, and depth
perception. Numerical data were plotted on a frequency histogram. Minitab
software was used to identify if individual metrics fit a standard distribution
curve. Analysis of variance was used to differentiate among 3 established
physician skill levels, as a means of assessing construct validity. RESULTS: In
the goodness-of-fit tests performed, angular path, depth perception, rotation,
and smoothness were found to best fit a log-normal distribution (p > 0.1).
Bimanual coordination was found to fit a normal distribution (p >= 0.067).
However, both normal and log-normal distributions were rejected (p <= 0.01) for
the metrics of time, volume, and economy of movement. After separating
participants into 3 groups based on level of experience with the Fundamentals of
Laparoscopic Surgery curriculum, analysis of variance showed significant
differences among all group means across the 5 metrics (i.e., angular path, depth
perception, rotation, smoothness, and bimanual coordination; p <= 0.023).
CONCLUSION: A proprietary device provided quantitative assessment of laparoscopic
skills, which can be used to differentiate among skill levels. Of the 8 tested
metrics, 5 fit a normal or log-normal distribution, meaning the scores can
statistically be ranked by percentile. Time, volume, and economy of movement did
not fit desired distributions. The grading system proved to have construct
validity, indicating it may be useful in the longitudinal assessment of
laparoscopic skills of surgical trainees.
PMID- 25127453
TI - Novel therapy for pyridoxine dependent epilepsy due to ALDH7A1 genetic defect: L
arginine supplementation alternative to lysine-restricted diet.
AB - BACKGROUND AND HYPOTHESIS: Pyridoxine dependent epilepsy (PDE) due to mutations
in the ALDH7A1 gene (PDE-ALDH7A1) is caused by alpha-aminoadipic-semialdehyde
dehydrogenase enzyme deficiency in the lysine pathway resulting in the
accumulation of alpha-aminoadipic acid semialdehyde (alpha-AASA). Classical
presentation is neonatal intractable seizures with a dramatic response to
pyridoxine. Pyridoxine therapy does not prevent developmental delays in the
majority of the patients. We hypothesized that L-arginine supplementation will
decrease accumulation of alpha-AASA by competitive inhibition of lysine transport
into the central nervous system and improve neurodevelopmental and neurocognitive
functions in PDE-ALDH7A1. METHODS: A 12-year-old male with PDE-ALDH7A1 was
treated with l-arginine supplementation as an innovative therapy. Treatment
outcome was monitored by cerebral-spinal-fluid (CSF) alpha-AASA measurements at
baseline, 6th and 12th months of therapy. Neuropsychological assessments were
performed at baseline and 12th months of therapy. RESULTS: L-arginine therapy was
well tolerated without side effects. CSF alpha-AASA was decreased 57% at 12th
months of therapy. Neuropsychological assessments revealed improvements in
general abilities index from 108 to 116 and improvements in verbal and motor
functioning at 12th months of therapy. CONCLUSION: The short-term treatment
outcome of this novel L-arginine supplementation therapy for PDE-ALDH7A1 was
successful for biochemical and neurocognitive improvements.
PMID- 25127454
TI - Moving to universal coverage? Trends in the burden of out-of-pocket payments for
health care across social groups in India, 1999-2000 to 2011-12.
AB - In the background of ongoing health sector reforms in India, the paper
investigates the magnitude and trends in out-of-pocket and catastrophic payments
for key population sub-groups. Data from three rounds of nationally
representative consumer expenditure surveys (1999-2000, 2004-05 and 2011-12) were
pooled to assess changes over time in a range of out-of-pocket -related outcome
indicators for the poorest 20% households, scheduled caste and tribe households
and Muslims households relative to their better-off/majority religion
counterparts. Our results suggest that the poorest 20% of households experienced
a decline in the proportion reporting any OOP for inpatient care relative to the
top 20% and Muslim households saw an increase in the proportion reporting any
inpatient OOP relative to non-Muslim households during 2000-2012. The change in
the proportion of Muslim households or SC/ST households reporting any OOP for
outpatient care was similar to that for their respective more advantaged
counterparts; but the poorest 20% of households experienced a faster increase in
the proportion reporting any OOP for outpatient care than their top 20%
counterparts. SC/ST, Muslim and the poorest 20% of households experienced as
faster increase in the share of outpatient OOP in total household spending
relative to their advantaged counterparts. We conclude that the financial burden
of out of pocket spending increased faster among the disadvantaged groups
relative to their more advantaged counterparts. Although the poorest 20% saw a
relative decline in OOP spending on inpatient care as a share of household
spending, this is likely the result of foregoing inpatient care, than of
accessing benefits from the recent expansion of cashless publicly financed
insurance schemes for inpatient care. Our results highlight the need to explore
the reasons underlying the lack of effectiveness of existing public health
financing programs and public sector health services in reaching less-advantaged
castes and religious minorities.
PMID- 25127455
TI - Patterns of tree species diversity in relation to climatic factors on the Sierra
Madre Occidental, Mexico.
AB - Biological diversity can be defined as variability among living organisms from
all sources, including terrestrial organisms, marine and other aquatic
ecosystems, and the ecological complexes which they are part of. This includes
diversity within species, between species, and of ecosystems. Numerous diversity
indices combine richness and evenness in a single expression, and several climate
based explanations have been proposed to explain broad-scale diversity patterns.
However, climate-based water-energy dynamics appears to be an essential factor
that determines patterns of diversity. The Mexican Sierra Madre Occidental
occupies an area of about 29 million hectares and is located between the
Neotropical and Holarctic ecozones. It shelters a high diversity of flora,
including 24 different species of Pinus (ca. 22% on the whole), 54 species of
Quercus (ca. 9-14%), 7 species of Arbutus (ca. 50%) and many other trees species.
The objectives of this study were to model how tree species diversity is related
to climatic and geographic factors and stand density and to test the Metabolic
Theory, Productivity-Diversity Hypothesis, Physiological Tolerance Hypothesis,
Mid-Domain Effect, and the Water-Energy Dynamic Theory on the Sierra Madre
Occidental, Durango. The results supported the Productivity-Diversity Hypothesis,
Physiological Tolerance Hypothesis and Water-Energy Dynamic Theory, but not the
Mid-Domain Effect or Metabolic Theory. The annual aridity index was the variable
most closely related to the diversity indices analyzed. Contemporary climate was
found to have moderate to strong effects on the minimum, median and maximum tree
species diversity. Because water-energy dynamics provided a satisfactory
explanation for the patterns of minimum, median and maximum diversity, an
understanding of this factor is critical to future biodiversity research.
Quantile regression of the data showed that the three diversity parameters of
tree species are generally higher in cold, humid temperate climates than in dry,
hot climates.
PMID- 25127457
TI - Cognitive dysfunction in Parkinson's disease related to the R1441G mutation in
LRRK2.
AB - OBJECTIVE: The neuropsychological characteristics of patients with Parkinson's
Disease (PD) associated with R1441G mutation in the LRRK2 gene (R1441G-PD) are
not well known. The aim of this study was to examine the cognitive status and
mood of R1441G-PD patients. METHODS: Thirty patients with R1441G-PD were compared
with thirty idiopathic PD (i-PD) patients who were matched by age, sex,
education, disease onset age and duration, using a comprehensive battery of
neuropsychological test, and considering the Movement Disorder Society (MDS)
criteria for the diagnosis of Mild Cognitive Impairment (PD-MCI) and dementia (PD
Dementia). RESULTS: The mean scores in the depression and anxiety scales were
similar in the two groups. Depressive symptoms were detected in 31.8% of R1441G
PD and 25% of i-PD patients and anxiety symptoms were evident in 4.5% and 15%,
respectively, but the differences were not significant. The only
neuropsychological test on which there was a significantly worse performance in
the R1441G-PD group was the Boston naming test but the difference became not
significant when Bonferroni's correction was applied. The prevalence of PD-MCI
was 30% in both R1441G-PD and i-PD, with no differences in the number and type of
domains altered given that executive function, memory and attention were mainly
affected. PD-Dementia was diagnosed in 13.3% (n = 4) of R1441G-PD and 26.7% (n =
8) of i-PD patients (difference was not significant). CONCLUSION: In conclusion,
significant differences were not detected between R1441G-PD and i-PD in
cognitive, depression and anxiety scales, or PD-MCI and PD-Dementia prevalence,
and the cognitive profile was identical in the two groups.
PMID- 25127456
TI - Benign and malignant nodular thyroid disease in acromegaly. Is a routine thyroid
ultrasound evaluation advisable?
AB - Data on the prevalence of benign and malignant nodular thyroid disease in
patients with acromegaly is a matter of debate. In the last decade an increasing
incidence of thyroid cancer has been reported. The aim of this study was to
evaluate the prevalence of goiter, thyroid nodules and thyroid cancer in a large
series of patients with acromegaly with a cross-sectional study with a control
group. Six Spanish university hospitals participated. One hundred and twenty
three patients (50% men; mean age 59+/-13 years; disease duration 6.7+/-7.2
years) and 50 controls (51% males, mean age 58+/-15 years) were studied. All
participants underwent thyroid ultrasound and fine needle aspiration. Cytological
analysis was performed in suspicious nodules between 0.5 and 1.0 cm and in all
nodules greater than 1.0 cm. Goiter was more frequently found in patients than in
controls (24.9 vs. 8.3%, respectively; p<0.001). Nodular thyroid disease as well
as nodules greater than 1 cm were also more prevalent in acromegalic patients
(64.6%, vs. 28.6%, p<0.05 and 53.3 vs. 28.6%, respectively; p<0.05), and all
underwent fine needle aspiration. Suspicious cytology was detected in 4 patients
and in none of the controls. After thyroidectomy, papillary thyroid carcinoma was
confirmed in two cases (3.3% of patients with thyroid nodules), representing 1.6%
of the entire group of patients with acromegaly (2.4% including a case with
previously diagnosed papillary thyroid carcinoma). These data indicated that
thyroid nodular disease and cancer are increased in acromegaly, thus justifying
its routine ultrasound screening.
PMID- 25127458
TI - A new highly sensitive method to assess respiration rates and kinetics of natural
planktonic communities by use of the switchable trace oxygen sensor and reduced
oxygen concentrations.
AB - Oxygen respiration rates in pelagic environments are often difficult to quantify
as the resolutions of our methods for O2 concentration determination are marginal
for observing significant decreases during bottle incubations of less than 24
hours. Here we present the assessment of a new highly sensitive method, that
combine Switchable Trace Oxygen (STOX) sensors and all-glass bottle incubations,
where the O2 concentration was artificially lowered. The detection limit of
respiration rate by this method is inversely proportional to the O2
concentration, down to <2 nmol L(-1) h(-1) for water with an initial O2
concentration of 500 nmol L(-1). The method was tested in Danish coastal waters
and in oceanic hypoxic waters. It proved to give precise measurements also with
low oxygen consumption rates (~7 nmol L(-1) h(-1)), and to significantly decrease
the time required for incubations (<=14 hours) compared to traditional methods.
This method provides continuous real time measurements, allowing for a number of
diverse possibilities, such as modeling the rate of oxygen decrease to obtain
kinetic parameters. Our data revealed apparent half-saturation concentrations (Km
values) one order of magnitude lower than previously reported for marine
bacteria, varying between 66 and 234 nmol L(-1) O2. Km values vary between
different microbial planktonic communities, but our data show that it is possible
to measure reliable respiration rates at concentrations ~0.5-1 umol L(-1) O2 that
are comparable to the ones measured at full air saturation.
PMID- 25127459
TI - The fate of nitrate in intertidal permeable sediments.
AB - Coastal zones act as a sink for riverine and atmospheric nitrogen inputs and
thereby buffer the open ocean from the effects of anthropogenic activity.
Recently, microbial activity in sandy permeable sediments has been identified as
a dominant source of N-loss in coastal zones, namely through denitrification.
Some of the highest coastal denitrification rates measured so far occur within
the intertidal permeable sediments of the eutrophied Wadden Sea. Still,
denitrification alone can often account for only half of the substantial nitrate
(NO3-) consumption. Therefore, to investigate alternative NO3- sinks such as
dissimilatory nitrate reduction to ammonium (DNRA), intracellular nitrate storage
by eukaryotes and isotope equilibration effects we carried out 15NO3- amendment
experiments. By considering all of these sinks in combination, we could quantify
the fate of the 15NO3- added to the sediment. Denitrification was the dominant
nitrate sink (50-75%), while DNRA, which recycles N to the environment accounted
for 10-20% of NO3- consumption. Intriguingly, we also observed that between 20
and 40% of 15NO3- added to the incubations entered an intracellular pool of NO3-
and was subsequently respired when nitrate became limiting. Eukaryotes were
responsible for a large proportion of intracellular nitrate storage, and it could
be shown through inhibition experiments that at least a third of the stored
nitrate was subsequently also respired by eukaryotes. The environmental
significance of the intracellular nitrate pool was confirmed by in situ
measurements which revealed that intracellular storage can accumulate nitrate at
concentrations six fold higher than the surrounding porewater. This intracellular
pool is so far not considered when modeling N-loss from intertidal permeable
sediments; however it can act as a reservoir for nitrate during low tide.
Consequently, nitrate respiration supported by intracellular nitrate storage can
add an additional 20% to previous nitrate reduction estimates in intertidal
sediments, further increasing their contribution to N-loss.
PMID- 25127461
TI - Novel N-biphenyl-2-ylmethyl 2-methoxyphenylpiperazinylalkanamides as 5-HT7R
antagonists for the treatment of depression.
AB - 5-HT7 receptor (5-HT7R) is a promising target for the treatment of depression and
neuropathic pain. 5-HT7R antagonists exhibited antidepressant effects, while the
agonists produced strong anti-hyperalgesic effects. In our efforts to discover
selective 5-HT7R antagonists or agonists, N-biphenylylmethyl 2
methoxyphenylpiperazinylalkanamides 1 were designed, synthesized, and
biologically evaluated against 5-HT7R. Among the synthesized compounds, N-2'
chlorobiphenylylmethyl 2-methoxyphenylpiperazinylpentanamide 1-8 showed the best
binding affinity with a Ki value of 8.69nM and it was verified as a novel
antagonist according to functional assays. The compound 1-8 was very selective
over 5-HT1DR, 5-HT2AR, 5-HT3R, 5-HT5AR and 5-HT6R and moderately selective over 5
HT1AR, 5-HT1BR and 5-HT2CR. The novel 5-HT7R antagonist 1-8 exhibited an
antidepressant effect at a dose of 25mg/kg in the forced swimming test in mice
and showed a U-shaped dose-response curve which typically appears in 5-HT7R
antagonists such as SB-269970 and lurasidone.
PMID- 25127462
TI - Synthesis and antifungal activity of substituted salicylaldehyde hydrazones,
hydrazides and sulfohydrazides.
AB - Efficient synthetic procedures for the preparation of acid hydrazines and
hydrazides were developed by converting the corresponding carboxylic acid into
the methyl ester catalyzed by Amberlyst-15, followed by a reaction with hydrazine
monohydrate. Sulfohydrazides were prepared from the corresponding sulfonyl
chlorides and hydrazine monohydrate. Both of these group of compounds were
condensed with substituted salicylaldehydes using gradient concentration methods
that generated a large library of hydrazone, hydrazide and sulfohydrazide
analogs. Antifungal activity of the prepared analogs showed that salicylaldehyde
hydrazones and hydrazides are potent inhibitors of fungal growth with little to
no mammalian cell toxicity, making these analogs promising new targets for future
therapeutic development.
PMID- 25127463
TI - 2-Phenylaminonaphthoquinones and related compounds: synthesis, trypanocidal and
cytotoxic activities.
AB - A series of new 2-aminonaphthoquinones and related compounds were synthesized and
evaluated in vitro as trypanocidal and cytotoxic agents. Some tested compounds
inhibited epimastigote growth and trypomastigote viability. Several compounds
showed similar or higher activity and selectivity as compared with current
trypanocidal drug, nifurtimox. Compound 4l exhibit higher selectivity than
nifurtimox against Trypanosoma cruzi in comparison with Vero cells. Some of the
synthesized quinones were tested against cancer cells and normal fibroblasts,
showing that certain chemical modifications on the naphthoquinone moiety induce
and excellent increase the selectivity index of the cytotoxicity (4g and 10). The
results presented here show that the anti-T. cruzi activity of 2
aminonaphthoquinones derivatives can be improved by the replacement of the
benzene ring by a pyridine moiety. Interestingly, the presence of a chlorine atom
at C-3 and a highly lipophilic alkyl group or aromatic ring are newly observed
elements that should lead to the discovery of more selective cytotoxic and
trypanocidal compounds.
PMID- 25127464
TI - Design, synthesis, and in vitro evaluation of an activity-based protein profiling
(ABPP) probe targeting agmatine deiminases.
AB - Agmatine deiminases (AgDs) belong to a family of enzymes known as guanidinium
group modifying enzymes (GMEs). Many pathogenic bacteria encode an AgD that
participates in the catabolism of agmatine (decarboxylated arginine). This
catabolism may confer a competitive survival advantage, by virtue of energy
production and increased acid tolerance, making this sub-family of enzymes a
potential therapeutic target that warrants further study. Herein we report the
development of an activity-based protein profiling (ABPP) probe that selectively
targets the AgD from Streptococcus mutans. Due to the selectivity and covalent
nature of the modification, this probe could prove to be a valuable tool for the
study of other AgD family members.
PMID- 25127465
TI - Identification of novel inhibitors of phospho-MurNAc-pentapeptide translocase
MraY from library screening: Isoquinoline alkaloid michellamine B and xanthene
dye phloxine B.
AB - The National Cancer Institute (NCI) Diversity Set was screened for potential
inhibitors of phospho-MurNAc-pentapeptide translocase MraY from Escherichia coli
using a primary fluorescence enhancement assay, followed by a secondary
radiochemical assay. One new MraY inhibitor was identified from this screen, a
naphthylisoquinoline alkaloid michellamine B, which inhibited E. coli MraY (IC50
456MUM) and Bacillus subtilis MraY (IC50 386MUM), and which showed antimicrobial
activity against B. subtilis (MIC 16MUg/mL). Following an earlier report of
halogenated fluoresceins identified from a combined MraY/MurG screen, three
halogenated fluoresceins were tested as inhibitors of E. coli MraY and E. coli
MurG, and phloxine B was identified as an inhibitor of E. coli MraY (IC50 32MUM).
Molecular docking of inhibitor structures against the structure of Aquifex
aeolicus MraY indicates that phloxine B appears to bind to the Mg(2+) cofactor in
the enzyme active site, while michellamine B binds to a hydrophobic groove formed
between transmembrane helices 5 and 9.
PMID- 25127466
TI - Exploiting the anti-HIV 6-desfluoroquinolones to design multiple ligands.
AB - It is getting clearer that many drugs effective in different therapeutic areas
act on multiple rather than single targets. The application of polypharmacology
concepts might have numerous advantages especially for disease such as HIV/AIDS,
where the rapid emergence of resistance requires a complex combination of more
than one drug. In this paper, we have designed three hybrid molecules combining
WM5, a quinolone derivative we previously identified as HIV Tat-mediated
transcription (TMT) inhibitor, with the tricyclic core of nevirapine and BILR
355BS (BILR) non-nucleoside reverse transcriptase inhibitors (NNRTIs) to
investigate whether it could be possible to obtain molecules acting on both
transcription steps of the HIV replicative cycle. One among the three designed
multiple ligands, reached this goal. Indeed, compound 1 inhibited both TMT and
reverse transcriptase (RT) activity. Unexpectedly, while the anti-TMT activity
exerted by compound 1 resulted into a selective inhibition of HIV-1 reactivation
from latently infected OM10.1 cells, the anti-RT properties shown by all of the
synthesized compounds did not translate into an anti-HIV activity in acutely
infected cells. Thus, we have herein produced the proof of concept that the
design of dual TMT-RT inhibitors is indeed possible, but optimization efforts are
needed to obtain more potent derivatives.
PMID- 25127467
TI - Sequence-specific DNA alkylation and transcriptional inhibition by long-chain
hairpin pyrrole-imidazole polyamide-chlorambucil conjugates targeting CAG/CTG
trinucleotide repeats.
AB - Introducing novel building blocks to solid-phase peptide synthesis, we readily
synthesized long-chain hairpin pyrrole-imidazole (PI) polyamide-chlorambucil
conjugates 3 and 4 via the introduction of an amino group into a GABA (gamma
turn) contained in 3, to target CAG/CTG repeat sequences, which are associated
with various hereditary disorders. A high-resolution denaturing polyacrylamide
sequencing gel revealed sequence-specific alkylation both strands at the N3 of
adenines or guanines in CAG/CTG repeats by conjugates 3 and 4, with 11bp
recognition. In vitro transcription assays using conjugate 4 revealed that
specific alkylation inhibited the progression of RNA polymerase at the alkylating
sites. Chiral substitution of the gamma-turn with an amino group resulted in
higher binding affinity observed in SPR assays. These assays suggest that
conjugates 4 with 11bp recognition has the potential to cause specific DNA damage
and transcriptional inhibition at the alkylating sites.
PMID- 25127468
TI - Ecological routes of avian influenza virus transmission to a common mesopredator:
an experimental evaluation of alternatives.
AB - BACKGROUND: Wild raccoons have been shown to be naturally exposed to avian
influenza viruses (AIV). However, the mechanisms associated with these natural
exposures are not well-understood. METHODOLOGY/PRINCIPAL FINDINGS: We
experimentally tested three alternative routes (water, eggs, and scavenged
waterfowl carcasses) of AIV transmission that may explain how raccoons in the
wild are exposed to AIV. Raccoons were exposed to 1) water and 2) eggs spiked
with an AIV (H4N6), as well as 3) mallard carcasses experimentally inoculated
with the same virus. Three of four raccoons exposed to the high dose water
treatment yielded apparent nasal shedding of >10(2.0) PCR EID50 equivalent/mL.
Little to no shedding was observed from the fecal route. The only animals
yielding evidence of serologic activity during the study period were three
animals associated with the high dose water treatment. CONCLUSIONS/SIGNIFICANCE:
Overall, our results indicate that virus-laden water could provide a natural
exposure route of AIV for raccoons and possibly other mammals associated with
aquatic environments. However, this association appears to be related to AIV
concentration in the water, which would constitute an infective dose. In
addition, strong evidence of infection was only detected in three of four animals
exposed to a high dose (e.g., 10(5.0) EID50/mL) of AIV in water. As such, water
borne transmission to raccoons may require repeated exposures to water with high
concentrations of virus.
PMID- 25127470
TI - Ultrasensitive electrochemical detection of microRNA with star trigon structure
and endonuclease mediated signal amplification.
AB - MicroRNAs play important roles in gene regulation. They can be used as effective
biomarkers for diagnosis and prognosis of diseases like cancers. Due to their
intrinsic properties of short length, low abundance and sequence homology among
family members, it is difficult to realize sensitive and selective detection with
economical use of time and cost. Herein, we report an ultrasensitive
electrochemical method for microRNA analysis employing two oligonucleotides and
one endonuclease. Generally, a glassy carbon electrode is first covered with gold
nanoparticles (AuNPs) mediated by poly(diallyldimethylammonium chloride) (PDDA).
Then, thiolated capture probe (CP) with methylene blue (MB) labeled at 5' end is
modified on the pretreated electrode. Hybridization occurs among target microRNA,
CP and auxiliary probe (AP), forming a star trigon structure on the electrode
surface. Subsequently, endonuclease recognizes and cleaves CP on CP/AP duplex,
releasing microRNA and AP back to the solution. The two regenerated elements can
then form another star trigon with other CP molecules, initiating cycles of CP
cleavage and MB departure. Significant decrease of electrochemical signals is
thus observed, which can be used to reflect the concentration of microRNA. This
proposed method has a linear response to microRNA in a wide range from 100 aM to
1 nM and the sensitivity of attomolar level can be achieved. Moreover, it has
high selectivity against single-base mismatch sequences and can be used directly
in serum samples. Therefore, this method shows great feasibility for the
detection of microRNA and may have potential applications in cancer diagnosis and
prognosis.
PMID- 25127469
TI - Evaluation of the contribution of multiple DAMPs and DAMP receptors in cell death
induced sterile inflammatory responses.
AB - When cells die by necrosis in vivo they stimulate an inflammatory response. It is
thought that this response is triggered when the injured cells expose
proinflammatory molecules, collectively referred to as damage associated
molecular patterns (DAMPs), which are recognized by cells or soluble molecules of
the innate or adaptive immune system. Several putative DAMPs and/or their
receptors have been identified, but whether and how much they participate in
responses in vivo is incompletely understood, and they have not previously been
compared side-by-side in the same models. This study focuses on evaluating the
contribution of multiple mechanisms that have been proposed to or potentially
could participate in cell death-induced inflammation: The third component of
complement (C3), ATP (and its receptor P2X7), antibodies, the C-type lectin
receptor Mincle (Clec4e), and protease-activated receptor 2 (PAR2). We
investigate the role of these factors in cell death-induced inflammation to dead
cells in the peritoneum and acetaminophen-induced liver damage. We find that mice
deficient in antibody, C3 or PAR2 have impaired inflammatory responses to dying
cells. In contrast there was no reduction in inflammation to cell death in the
peritoneum or liver of mice that genetically lack Mincle, the P2X7 receptor or
that were treated with apyrase to deplete ATP. These results indicate that
antibody, complement and PAR2 contribute to cell death-induced inflammation but
that Mincle and ATP- P2X7 receptor are not required for this response in at least
2 different in vivo models.
PMID- 25127471
TI - Screen-printed microfluidic dielectrophoresis chip for cell separation.
AB - Dielectrophoresis (DEP), the induced motion of polarizable particles in a non
uniform electric field, has been proven as a perfect candidate to transport,
accumulate, separate and characterize micro-/nano-scale bioparticles in
microfluidic systems. However, conventional fabrication technologies are complex,
time-consuming and relatively expensive, leading to low throughput of the DEP
based systems. In this paper, we report a novel microfluidic alternating current
DEP (AC-DEP) chip fabricated via inexpensive screen printing method. The
innovation of our work consists in the extreme simplicity of the fabrication
procedure, i.e., the main components, including electrodes and channels, were
constructed by layer-by-layer screen printing process, which is especially
suitable for high-throughput mass production. Carbon paste, instead of metals,
was used to print interdigitated electrodes with semi-3D structure which not only
reduces dramatically the chip cost but also increases particle trapping
efficiency. To test the chip performance, yeast cells, as model cells, were
trapped and separated from a mixed suspension with PS microspheres. Our results
show that high capture rate and separation efficiency can be achieved under
optimized conditions.
PMID- 25127472
TI - A cost-effective Z-folding controlled liquid handling microfluidic paper analysis
device for pathogen detection via ATP quantification.
AB - A cost-effective microfluidic paper analysis device (MUPAD) was developed with a
special Z-folding design for controlling the fluidic flowing and substrate
transportation. This presented MUPAD can be easily fabricated through wax
printing by using a solid ink printer which deposits wax onto the surface of a
chromatographic paper, and then baked on a hotplate by penetrating the molten wax
into the paper to create a hydrophobic barrier. After MUPAD fabrication, liquid
control and substrate transportation can be easily carried out by twice folding
the MUPAD following Z shape. The Z folding made two separated reagent holding
zone connected while the detection reaction occurred with the connection. In this
paper, a pathogens detection indicated by ATP quantification was took as a proof
in-principle application of using this presented MUPAD, the limit of detection
(LOD) was 1 MUM for ATP detection and 2.6*10(7) CFU/mL for Salmonella live cell
detection, which showed a great potential for Point-of-Care Testing (POCT)
applications.
PMID- 25127473
TI - The peroxidase/catalase-like activities of MFe2O4 (M=Mg, Ni, Cu) MNPs and their
application in colorimetric biosensing of glucose.
AB - MFe2O4 (M=Mg, Ni, Cu) magnetic nanoparticles (MNPs) were found to have catalytic
activities similar to those of biological enzymes such as catalase and
peroxidase. These nanomaterials, as bifunctional catalase/peroxidases (KatGs),
not only could catalyze H2O2 to produce hydroxyl radicals, which oxidized
peroxidase substrate to produce color, but also could catalyze the decomposition
reaction of H2O2 into water and oxygen directly in the same condition through the
catalase-like activity. And it was also found that the amount of generated
hydroxyl radicals and oxygen was related to the concentration of MFe2O4 (M=Mg,
Ni, Cu) MNPs. The peroxidase-like catalytic behavior of MFe2O4 MNPs was analyzed
in detail. Under the optimized conditions, NiFe2O4 MNPs were used as a
colorimetric biosensor for the detection of 9.4*10(-7)-2.5*10(-5) mol L(-1)
glucose with a limit of detection (LOD) of 4.5*10(-7) mol L(-1). The sensor was
successfully applied to glucose detection in urine sample.
PMID- 25127474
TI - Development of highly sensitive electrochemical genosensor based on multiwalled
carbon nanotubes-chitosan-bismuth and lead sulfide nanoparticles for the
detection of pathogenic Aeromonas.
AB - In this paper, we reported the construction of new high sensitive electrochemical
genosensor based on multiwalled carbon nanotubes-chitosan-bismuth complex (MWCNT
Chi-Bi) and lead sulfide nanoparticles for the detection of pathogenic Aeromonas.
Lead sulfide nanoparticles capped with 5'-(NH2) oligonucleotides thought amide
bond was used as signalizing probe DNA (sz-DNA) and thiol-modified
oligonucleotides sequence was used as fixing probe DNA (fDNA). The two probes
hybridize with target Aeromonas DNA (tDNA) sequence (fDNA-tDNA-szDNA). The signal
of hybridization is detected by differential pulse voltammetry (DPV) after
electrodeposition of released lead nanoparticles (PbS) from sz-DNA on the surface
of glass carbon electrode decorated with MWCNT-Chi-Bi, which improves the
deposition and traducing electrical signal. The optimization of incubation time,
hybridization temperature, deposition potential, deposition time and the
specificity of the probes were investigated. Our results showed the highest
sensibility to detect the target gene when compared with related biosensors and
polymerase chain reaction (PCR). The detection limit for this biosensor was
1.0*10(-14) M. We could detect lower than 10(2) CFU mL(-1) of Aeromonas in spiked
tap water. This method is rapid and sensitive for the detection of pathogenic
bacteria and would become a potential application in biomedical diagnosis, food
safety and environmental monitoring.
PMID- 25127475
TI - Electrochemical biosensor for carbofuran pesticide based on esterases from
Eupenicillium shearii FREI-39 endophytic fungus.
AB - In this work, a biosensor was constructed by physical adsorption of the isolated
endophytic fungus Eupenicillium shearii FREI-39 esterase on halloysite, using
graphite powder, multi-walled carbon nanotubes and mineral oil for the
determination of carbofuran pesticide by inhibition of the esterase using square
wave voltammetry (SWV). Specific esterase activities were determined each 2 days
over a period of 15 days of growth in four different inoculation media. The
highest specific activity was found on 6th day, with 33.08 U on PDA broth. The
best performance of the proposed biosensor was obtained using 0.5 U esterase
activity. The carbofuran concentration response was linear in the range from 5.0
to 100.0 ug L(-1) (r=0.9986) with detection and quantification limits of 1.69 ug
L(-1) and 5.13 ug L(-1), respectively. A recovery study of carbofuran in spiked
water samples showed values ranging from 103.8+/-6.7% to 106.7+/-9.7%. The
biosensor showed good repeatability and reproducibility and remained stable for a
period of 20 weeks. The determination of carbofuran in spiked water samples using
the proposed biosensor was satisfactory when compared to the chromatographic
reference method. The results showed no significant difference at the 95%
confidence level with t-test statistics. The application of enzymes from
endophytic fungi in constructing biosensors broadens the biotechnological
importance of these microorganisms.
PMID- 25127476
TI - Associations between rice, noodle, and bread intake and sleep quality in Japanese
men and women.
AB - BACKGROUND: Previous studies have shown that a diet with a high-glycemic index is
associated with good sleep quality. Therefore, we investigated the association of
sleep quality with the intake of 3 common starchy foods with different glycemic
indexes-rice, bread, and noodles-as well as the dietary glycemic index in a
Japanese population. METHODS: The participants were 1,848 men and women between
20 and 60 years of age. Rice, bread, and noodle consumption was evaluated using a
self-administered diet history questionnaire. Sleep quality was evaluated by
using the Japanese version of the Pittsburgh Sleep Quality Index, and a global
score >5.5 was considered to indicate poor sleep. RESULTS: Multivariate-adjusted
odds ratios (95% confidence intervals) for poor sleep across the quintiles of
rice consumption were 1.00 (reference), 0.68 (0.49-0.93), 0.61 (0.43-0.85), 0.59
(0.42-0.85), and 0.54 (0.37-0.81) (p for trend = 0.015); those for the quintiles
of noodle consumption were 1.00 (reference), 1.25 (0.90-1.74), 1.05 (0.75-1.47),
1.31 (0.94-1.82), and 1.82 (1.31-2.51) (p for trend = 0.002). Bread intake was
not associated with sleep quality. A higher dietary glycemic index was
significantly associated with a lower risk of poor sleep (p for trend = 0.020).
CONCLUSION: A high dietary glycemic index and high rice consumption are
significantly associated with good sleep in Japanese men and women, whereas bread
intake is not associated with sleep quality and noodle consumption is associated
with poor sleep. The different associations of these starchy foods with sleep
quality might be attributable to the different glycemic index of each food.
PMID- 25127477
TI - Helium generated cold plasma finely regulates activation of human fibroblast-like
primary cells.
AB - Non-thermal atmospheric pressure plasmas are being developed for a wide range of
health care applications, including wound healing. However in order to exploit
the potential of plasma for clinical applications, the understanding of the
mechanisms involved in plasma-induced activation of fibroblasts, the cells active
in the healing process, is mandatory. In this study, the role of helium generated
plasma in the tissue repairing process was investigated in cultured human
fibroblast-like primary cells, and specifically in hepatic stellate cells and
intestinal subepithelial myofibroblasts. Five minutes after treatment, plasma
induced formation of reactive oxygen species (ROS) in cultured cells, as assessed
by flow cytometric analysis of fluorescence-activated 2',7'-dichlorofluorescein
diacetate probe. Plasma-induced intracellular ROS were characterized by lower
concentrations and shorter half-lives with respect to hydrogen peroxide-induced
ROS. Moreover ROS generated by plasma treatment increased the expression of
peroxisome proliferator activated receptor (PPAR)-gamma, nuclear receptor that
modulates the inflammatory responses. Plasma exposure promoted wound healing in
an in vitro model and induced fibroblast migration and proliferation, as
demonstrated, respectively, by trans-well assay and partitioning between daughter
cells of carboxyfluorescein diacetate succinimidyl ester fluorescent dye. Plasma
induced fibroblast migration and proliferation were found to be ROS-dependent as
cellular incubation with antioxidant agents (e.g. N-acetyl L-cysteine) cancelled
the biological effects. This study provides evidence that helium generated plasma
promotes proliferation and migration in liver and intestinal fibroblast-like
primary cells mainly by increasing intracellular ROS levels. Since plasma-evoked
ROS are time-restricted and elicit the PPAR-gamma anti-inflammatory molecular
pathway, this strategy ensures precise regulation of human fibroblast activation
and can be considered a valid therapeutic approach for liver and gut lesions.
PMID- 25127479
TI - Buckley-James estimator of AFT models with auxiliary covariates.
AB - In this paper we study the Buckley-James estimator of accelerated failure time
models with auxiliary covariates. Instead of postulating distributional
assumptions on the auxiliary covariates, we use a local polynomial approximation
method to accommodate them into the Buckley-James estimating equations. The
regression parameters are obtained iteratively by minimizing a consecutive
distance of the estimates. Asymptotic properties of the proposed estimator are
investigated. Simulation studies show that the efficiency gain of using auxiliary
information is remarkable when compared to just using the validation sample. The
method is applied to the PBC data from the Mayo Clinic trial in primary biliary
cirrhosis as an illustration.
PMID- 25127481
TI - Do diabetic kidneys deserve a lifestyle change?
PMID- 25127478
TI - Disruption of axonal transport perturbs bone morphogenetic protein (BMP)-
signaling and contributes to synaptic abnormalities in two neurodegenerative
diseases.
AB - Formation of new synapses or maintenance of existing synapses requires the
delivery of synaptic components from the soma to the nerve termini via axonal
transport. One pathway that is important in synapse formation, maintenance and
function of the Drosophila neuromuscular junction (NMJ) is the bone morphogenetic
protein (BMP)-signaling pathway. Here we show that perturbations in axonal
transport directly disrupt BMP signaling, as measured by its downstream signal,
phospho Mad (p-Mad). We found that components of the BMP pathway genetically
interact with both kinesin-1 and dynein motor proteins. Thick vein (TKV) vesicle
motility was also perturbed by reductions in kinesin-1 or dynein motors.
Interestingly, dynein mutations severely disrupted p-Mad signaling while kinesin
1 mutants showed a mild reduction in p-Mad signal intensity. Similar to mutants
in components of the BMP pathway, both kinesin-1 and dynein motor protein mutants
also showed synaptic morphological defects. Strikingly TKV motility and p-Mad
signaling were disrupted in larvae expressing two human disease proteins;
expansions of glutamine repeats (polyQ77) and human amyloid precursor protein
(APP) with a familial Alzheimer's disease (AD) mutation (APPswe). Consistent with
axonal transport defects, larvae expressing these disease proteins showed
accumulations of synaptic proteins along axons and synaptic abnormalities. Taken
together our results suggest that similar to the NGF-TrkA signaling endosome, a
BMP signaling endosome that directly interacts with molecular motors likely
exist. Thus problems in axonal transport occurs early, perturbs BMP signaling,
and likely contributes to the synaptic abnormalities observed in these two
diseases.
PMID- 25127480
TI - Developmental exposure of mice to dioxin promotes transgenerational testicular
inflammation and an increased risk of preterm birth in unexposed mating partners.
AB - TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly known as dioxin) is a
ubiquitous environmental contaminant and known endocrine disruptor. Using a mouse
model, we previously found that adult female mice exposed in utero to TCDD (F1
generation) as well as multiple subsequent generations (F2-F4) exhibited reduced
fertility and an increased incidence of spontaneous preterm birth. Additional
studies revealed that male F1 mice with a similar in utero/developmental TCDD
exposure also exhibited diminished fertility and conferred an increased risk of
preterm birth to their unexposed mating partners. Herein, we extend these
previous observations, reporting that reduced fertility in male F1 mice is linked
to testicular inflammation which coincides with apoptosis of developing
spermatocytes, sub-fertility and an increased risk of preterm birth in their
unexposed mating partners. Significantly, in the absence of additional toxicant
exposure, testicular inflammation and reduced fertility persisted in F2 and F3
males and their control mating partners also frequently exhibited spontaneous
preterm birth. Although a steady, global decline in male fertility has been noted
over the last few decades, the reasons for these changes have not been firmly
established. Likewise, the PTB rate in the U.S. and other countries has
paralleled industrial development, suggesting a possible relationship between
environmental toxicant exposure and adverse pregnancy outcomes. Most current
clinical strategies to prevent preterm birth are focused solely on the mother and
have yielded limited benefits. In contrast, our studies strongly suggest that the
preconception testicular health of the father is a critical determinant of
pregnancy outcomes in mice. Future clinical studies should examine the potential
contribution of the male to gestation length in women and whether efforts to
reduce the incidence of preterm birth should be initiated in both parents prior
to pregnancy.
PMID- 25127482
TI - Combining incretin-based drugs and RAAS inhibitors: more cons than pros?
PMID- 25127484
TI - Jenny Graves: the free spirit of scientific enquiry.
PMID- 25127485
TI - Selective deficit of spatial short-term memory: Role of storage and rehearsal
mechanisms.
AB - We report the neuropsychological and MRI investigation of a patient (GP) who
developed a selective impairment of spatial short-term memory (STM) following
damage to the dorso-mesial areas of the right frontal lobe. We assessed in this
patient spatial STM with an experimental procedure that evaluated immediate and 5
20 s delayed recall of verbal, visual and spatial stimuli. The patient scored
significantly worse than normal controls on tests that required delayed recall of
spatial data. This could not be ascribed to a deficit of spatial episodic long
term memory because amnesic patients performed normally on these tests.
Conversely, the patient scored in the normal range on tests of immediate recall
of verbal, visual and spatial data and tests of delayed recall of verbal and
visual data. Comparison with a previously described patient who had a selective
deficit in immediate spatial recall and an ischemic lesion that affected frontal
and parietal dorso-mesial areas in the right hemisphere (Carlesimo GA, Perri R,
Turriziani P, Tomaiuolo F, Caltagirone C. Remembering what but not where:
independence of spatial and visual working memory in the human brain. Cortex.
2001 Sep; 37(4):519-34) suggests that the right parietal areas are involved in
the short-term storage of spatial information and that the dorso-mesial regions
of the right frontal underlie mechanisms for the delayed maintenance of the same
data.
PMID- 25127486
TI - Multiplexed gold nanorod array biochip for multi-sample analysis.
AB - Optical transduction of biological bindings based on localized surface plasmon
resonance (LSPR) of gold nanorods (GNRs) is attractive for label-free biosensing.
The aspect ratio (AR) dependence of LSPR band maxima inherently provides an ideal
multiplex mechanism. GNRs of selected sizes can be combined to ensure distinct
plasmon peaks in absorption spectrum. Monitoring the spectral shift at the
dedicated peaks allows for simultaneous detection of the specific analyte. Here,
we first transformed the GNR's multiplexed biosensing capability to a robust chip
based format. Specifically, nanorods of AR 2.6 and 4.5 were assembled onto thiol
terminated substrates, followed by functionalization of respective antibodies to
construct a GNR multiplex biochip. As a model system, concentrations of human IgG
and rabbit IgG were simultaneously measured by correlating red-shifts at distinct
resonance peaks caused by specific target binding. The calibration curves
exhibited linear relationship between the spectral shift and analyte amount. The
sensing performance in multi-analyte mode correlated nicely with those for single
analyte detection with minimal cross-reactivity. Moreover, mixed GNRs can be
deposited in controllable array pattern on the glass chip to analyze numerous
samples at the same time. Each GNRs dot functioned independently as a multiplexed
plamonic sensor. Coupled with microplate reader, this GNR nanoarray chip can
potentially result in large scale assay of samples concurrently while for each
sample, a multi-analyte detection simultaneously if desired. The concept shown in
this work is simple and versatile that will definitely be a new paradigm in high
throughput protein biochip development in the era of nano-biosensing.
PMID- 25127483
TI - Effect of a long-term behavioural weight loss intervention on nephropathy in
overweight or obese adults with type 2 diabetes: a secondary analysis of the Look
AHEAD randomised clinical trial.
AB - BACKGROUND: Long-term effects of behavioural weight loss interventions on
diabetes complications are unknown. In a secondary analysis of the Look AHEAD
(Action for Health in Diabetes) multicentre randomised clinical trial, we
assessed whether an intensive lifestyle intervention (ILI) affects the
development of nephropathy in people with type 2 diabetes. METHODS: Overweight or
obese people aged 45-76 years with type 2 diabetes were randomly assigned (1:1)
to ILI or to a diabetes support and education (DSE) group by a central web-based
data management system, stratified by clinical centre and blocked with random
block sizes. The ILI was designed to achieve and maintain weight loss through
reduced caloric consumption and increased physical activity. The interventions
were terminated early because of absence of effect on the primary outcome of
cardiovascular disease events in the main Look AHEAD trial. Albuminuria and
estimated glomerular filtration rate were prespecified as two of many other
outcomes and were assessed from baseline until the interventions ended. They were
combined post hoc to define the main outcome for this report, very-high-risk
chronic kidney disease (CKD), based on the 2013 Kidney Disease Improving Global
Outcomes (KDIGO) classification. Outcomes assessors and laboratory staff were
masked to treatment, but participants and interventionists were not masked. Time
to-event data were analysed by intention to treat by the Kaplan-Meier method and
proportional hazards models. The Look AHEAD trial is registered with
ClinicalTrials.gov, NCT00017953. FINDINGS: Of the 5145 participants randomly
assigned in the Look AHEAD trial (2570 to ILI and 2575 to DSE), analyses for very
high-risk CKD were done in 2423 (94%) of patients in the ILI group and 2408 (94%)
of those in the DSE group. After a median of 8.0 years (IQR 7.9-9.9) of follow
up, the incidence of very-high-risk CKD was lower in the ILI group than in the
DSE group, with incidence rates of 0.91 cases per 100 person-years in the DSE
group and 0.63 per 100 person-years in the ILI group (difference 0.27 cases per
100 person-years, hazard ratio 0.69, 95% CI 0.55-0.87; p=0.0016). This effect was
partly attributable to reductions in bodyweight, HbA1c, and systolic blood
pressure. There were no safety concerns regarding kidney-related adverse events.
INTERPRETATION: Weight loss should be considered as an adjunct to medical
treatments to prevent or delay progression of CKD in overweight or obese people
with type 2 diabetes. FUNDING: National Institute of Diabetes and Digestive and
Kidney Diseases.
PMID- 25127487
TI - Multi-level kinetic model explaining diverse roles of isozymes in prokaryotes.
AB - Current standard methods for kinetic and genomic modeling cannot provide deep
insight into metabolic regulation. Here, we developed and evaluated a multi-scale
kinetic modeling approach applicable to any prokaryote. Specifically, we
highlight the primary metabolism of the cyanobacterium Synechococcus elongatus
PCC 7942. The model bridges metabolic data sets from cells grown at different CO2
conditions by integrating transcriptomic data and isozymes. Identification of the
regulatory roles of isozymes allowed the calculation and explanation of the
absolute metabolic concentration of 3-phosphoglycerate. To demonstrate that this
method can characterize any isozyme, we determined the function of two glycolytic
glyceraldehyde-3-phosphate dehydrogenases: one co-regulates high concentrations
of the 3-phosphoglycerate, the other shifts the bifurcation point in hexose
regulation, and both improve biomass production. Moreover, the regulatory roles
of multiple phosphoglycolate phosphatases were defined for varying (non-steady)
CO2 conditions, suggesting their protective role against toxic photorespiratory
intermediates.
PMID- 25127488
TI - Design changes improve contact patterns and articular surface damage in total
knee arthroplasty.
AB - BACKGROUND: The Optetrak PS (Exactech, Inc., Gainesville, FL) has been a well
functioning posterior stabilized knee replacement since its introduction in 1995.
In 2009, the Optetrak Logic incorporated modifications to the anterior face of
the tibial post and the corresponding anterior articulating surface of the
femoral component to reduce edge loading on the polyethylene post. In this study,
we provide the rationale for the design change and compare the damage on
retrieved tibial components of both designs to demonstrate the effectiveness of
the design modifications in decreasing post damage. METHODS: We integrated
retrieval findings of tibial post damage with finite element analysis to redesign
the anterior tibial post-femoral box articulation. We then used subsequent
retrieval analysis on a 3:1 matched sample of 60 PS and 20 Logic inserts to
examine the impact of the design change on polyethylene damage. RESULTS:
Polyethylene stresses were markedly reduced when rounded contact geometries were
incorporated. The comparison of the new and old designs using retrieval analysis
demonstrated that the redesign led to reduction in surface damage and deformation
on the tibial post. CONCLUSIONS: This study shows the use of a design cycle by
which a problem is identified through retrieval analysis, analytical tools are
used to suggest design solutions, and then retrieval analysis is applied again on
the new design to confirm improved performance. CLINICAL RELEVANCE: Anterior post
damage has been markedly reduced through the introduction of design changes to
the post-box geometry.
PMID- 25127489
TI - N-acetyl-4-aminophenol (paracetamol) in urine samples of 6-11-year-old Danish
school children and their mothers.
AB - Recent studies indicate an association between the use of paracetamol during
pregnancy and reproductive disorders in male offspring. Furthermore, N-acetyl-4
aminophenol (NAAP, paracetamol) has been shown to be ubiquitously excreted in
urine samples of the general population. To investigate the internal body burden
of the Danish population to NAAP for the first time, 288 morning urine samples
from 6- to 11-year-old Danish school children and their mothers were analyzed for
NAAP. NAAP was measurable in all mothers and all of the children except for one
child. Results showed that there is a ubiquitous body burden of NAAP in Danish
mothers and children even when paracetamol analgesics have not been used
recently. Hence, several unknown sources of NAAP/paracetamol exposure have to
exist. We found an association in NAAP excretion between the mothers and their
children which could indicate common lifestyle related exposure (e.g. via food or
indoor air sources). However, we did not detect any association between lifestyle
data from questionnaires and levels of NAAP excretion in this study. The
knowledge about possible sources of exposure leading to this omnipresent
paracetamol excretion is limited and further investigation is wanted.
PMID- 25127491
TI - Analysis of muscle activation patterns during transitions into and out of high
knee flexion postures.
AB - Increased risk of medial tibiofemoral osteoarthritis (OA) is linked to
occupations that require frequent transitions into and out of postures which
require high knee flexion (>90 degrees ). Muscle forces are major contributors to
joint loading, and an association between compressive forces due to muscle
activations and the degeneration of joint cartilage has been suggested. The
purpose of this study was to evaluate muscle activation patterns of muscles
crossing the knee during transitions into and out of full-flexion kneeling and
squatting, sitting in a low chair, and gait. Both net and co-activation were
greater when transitioning out of high flexion postures, with maximum activation
occurring at knee angles greater than 100 degrees . Compared to gait, co
activation levels during high flexion transitions were up to approximately 3
times greater. Co-activation was significantly greater in the lateral muscle
group compared to the medial group during transitions into and out of high
flexion postures. These results suggest that compression due to activation of the
medial musculature of the knee may not be the link between high knee flexion
postures and increased medial knee OA observed in occupational settings. Further
research on a larger subject group and workers with varying degrees of knee OA is
necessary.
PMID- 25127490
TI - PCBs, PCDD/Fs, and PBDEs in blood samples of a rural population in South Germany.
AB - The body burden of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs),
dioxin-like (dl-PCBs) and non-dioxin-like (ndl-PCBs) polychlorinated biphenyls,
and polybrominated diphenyl ethers (PBDEs) was determined in blood samples from
70 subjects between 4 and 76 years old. The participants of the study were
recruited in the neighborhood of a reclamation plant located in a rural area in
Southern Germany. The median concentrations (95th percentiles in parentheses),
expressed as WHO2005-TEQ (toxic equivalents), for PCDD/Fs and dl-PCBs were 4.5
(17.9)pgg(-1) l.w. and 2.6 (13.2)pgg(-1) l.w., respectively. The dl-PCBs
contributed 40% of the total TEQ (median values), and the most abundant congener
was PCB 156. Combined, the sum of the 6 non-dioxin-like PCBs had a median of
0.773MUgL(-1) and a 95th percentile of 4.895MUgL(-1). For the six tetra to hepta
PBDE congeners, the median was 1.8ngg(-1) l.w. (95th percentile: 16.2ngg(-1)
l.w.). None of our study subjects had a body burden that exceeded the
biomonitoring equivalents for dioxins or PBDE congener 99 or the human
biomonitoring values for ndl-PCBs. Likewise the study group did not exceed German
reference values or values obtained in similar investigations. Overall, our study
did not exhibit elevated internal exposures. The results also hint further
decreasing tendencies for PCDD/Fs, PCBs, and PBDEs in Germany and demonstrates
that people in the vicinity of a reclamation plant with no indication of an
environmental contamination did not exhibit elevated internal exposures.
PMID- 25127492
TI - Altered corticomuscular coherence elicited by paced isotonic contractions in
individuals with cerebral palsy: a case-control study.
AB - The purpose of the study was to analyze corticomuscular coherence during planning
and execution of simple hand movements in individuals with cerebral palsy (CP)
and healthy controls (HC). Fourteen individuals with CP and 15 HC performed
voluntary paced movements (opening and closing the fist) in response to a warning
signal. Simultaneous scalp EEG and surface EMG of extensor carpi radialis brevis
were recorded during 15 isotonic contractions. Time-frequency corticomuscular
coherence (EMG-C3/C4) before and during muscular contraction, as well as EMG
intensity, onset latency and duration were analyzed. Although EMG intensity was
similar in both groups, individuals with CP exhibited longer onset latency and
increased duration of the muscular contraction than HC. CP also showed higher
corticomuscular coherence in beta EEG band during both planning and execution of
muscular contraction, as well as lower corticomuscular coherence in gamma EEG
band at the beginning of the contraction as compared with HC. In conclusion, our
results suggest that individuals with CP are characterized by an altered
functional coupling between primary motor cortex and effector muscles during
planning and execution of isotonic contractions. In addition, the usefulness of
corticomuscular coherence as a research tool for exploring deficits in motor
central processing in persons with early brain damage is discussed.
PMID- 25127493
TI - Reliability of telemetric electromyography and near-infrared spectroscopy during
high-intensity resistance exercise.
AB - This study quantified the inter- and intra-test reliability of telemetric surface
electromyography (EMG) and near infrared spectroscopy (NIRS) during resistance
exercise. Twelve well-trained young men performed high-intensity back squat
exercise (12 sets at 70-90% 1-repetition maximum) on two occasions, during which
EMG and NIRS continuously monitored muscle activation and oxygenation of the
thigh muscles. Intra-test reliability for EMG and NIRS variables was generally
higher than inter-test reliability. EMG median frequency variables were generally
more reliable than amplitude-based variables. The reliability of EMG measures was
not related to the intensity or number of repetitions performed during the set.
No notable differences were evident in the reliability of EMG between different
agonist muscles. NIRS-derived measures of oxyhaemoglobin, deoxyhaemoglobin and
tissue saturation index were generally more reliable during single-repetition
sets than multiple-repetition sets at the same intensity. Tissue saturation index
was the most reliable NIRS variable. Although the reliability of the EMG and NIRS
measures varied across the exercise protocol, the precise causes of this
variability are not yet understood. However, it is likely that biological
variation during multi-joint isotonic resistance exercise may account for some of
the variation in the observed results.
PMID- 25127494
TI - Pathophysiology of the constant burning, tingling element of neuropathic pain: a
new hypothesis.
AB - Neuropathic pain (NPP) presents itself with at least one of the following
elements: constant, intermittent and evoked pain. The pathophysiology of NPP is
still controversial, in especial of its constant element, the focus of this
study. Many hypotheses have been proposed in an attempt to explain it, but none
of them seems to account for the various aspects of the constant element of NPP.
Under the phylogenetic perspective, it is postulated, the pain may be classified
into two categories: paleopain, present in inferior animals, poorly localized,
transmitted by the medial pain system pathways, and neopain, conducted by the
lateral pain system pathways, very well localized, described in terms suggestive
of tissue damage and present in superior animals. We believe that, in humans,
under physiological circumstances, the expression of the paleopain was completely
abolished. It is proposed that it is due to the tonic inhibition of the medial
thalamus by the ventral posterior (VP) nucleus of the thalamus, via a circuit
that the authors described and named prosencephalomesencephalic modulatory
circuit (PMMC). Two pathways are suggested as activators of the PMMC: the
neospinothalamic/neotrigeminothalamic and ventral spinothalamic tracts. The
interruption of this circuit or of its activators, at any point, would lead to
the release of the medial thalamus from the inhibitory influences of VP, allowing
the manifestation of the paleopain. It is postulated that the constant burning,
tingling element of NPP is nothing more than the clinical expression of the
paleopain. Evidence to support this hypothesis is provided. As a direct
consequence of the presented hypothesis, the substantia nigra pars reticulata is
proposed as a new target of deep brain stimulation for the treatment of the
constant burning, tingling element of NPP.
PMID- 25127495
TI - Aristotle got it right again!
PMID- 25127497
TI - Persistent organic pollutants in liver of Brazilian sharpnose shark
(Rhizoprionodon lalandii) from southeastern coast of Brazil.
AB - In the present study, persistent organic pollutants (POPs) were determined in 14
livers from specimens of the Brazilian sharpnose shark (Rhizoprionodon lalandii),
which is an important economic resource for small-scale fisheries on the
southeastern coast of Brazil. The following concentrations (lipid weight) of POPs
were found: ?PCBs: 1019+/-267 ng g(-1); ?DDTs: 111+/-40 ng g(-1) and ?PBDEs:
10.4+/-4.78. PCB 153 made the greatest contribution to ?PCB (21.4%), followed by
PCB 138 (14.6%) and PCB 180 (9.94%). Among chlorinated pesticides, only the p,p'
DDE and p,p'-DDD isomers had concentrations above the detection limit. Moreover,
levels above the detection limit were found only for PBDE congeners 47 and 100
(BDEs 47>99). On average, BDE 47 accounted for 88% of the total PBDE load. The
feeding habits of the Brazilian sharpnose shark close to the Brazilian coastline
are likely the most important difference regarding the accumulation of POPs in
comparison to oceanic species that feed in deeper waters. Thus, this species may
be used to evaluate the pollution of coastal areas as well as human exposure to
contaminants, as the Brazilian sharpnose shark is a frequently used for human
consumption. Further studies in other areas of Brazil and involving other species
are needed to clarify the mechanisms and potential impact of POPs, which can
affect the biology of different organisms and cause population declines.
PMID- 25127498
TI - Steroid markers to assess sewage and other sources of organic contaminants in
surface sediments of Cienfuegos Bay, Cuba.
AB - Analyses of faecal steroids in coastal sediments from Cienfuegos Bay Cuba
indicate chronic sewage contamination at the main outfalls from the city, where
concentrations of coprostanol up to 5400ngg(-)(1) (dry wt) were measured. In
contrast, steroid concentrations and compositions from sites from the south part
of the Bay are characteristic of uncontaminated sewage environments. The levels
of coprostanol in the Cienfuegos sediments compares to the lower to mid-range of
concentrations reported for coastal sediments on a world-wide basis, with
sedimentary levels markedly below those previously reported for heavily impacted
sites. This study delivers baseline data for further investigation of the
effectiveness of the proposed sewerage plan promoted by the GEF project in
Cienfuegos. Investigations on the correlations between faecal steroids and other
organic contaminants confirmed that the major source of petroleum hydrocarbons
within the bay was associated with the sewage effluents from the Cienfuegos city.
PMID- 25127499
TI - Response of multi-metric indices to anthropogenic pressures in distinct marine
habitats: the need for recalibration to allow wider applicability.
AB - Sustainable exploitation of coastal ecosystems is facilitated by tools which
allow reliable assessment of their response to anthropogenic pressures. The
Infaunal Quality Index (IQI) and Multivariate-AMBI (M-AMBI) were developed to
classify the ecological status (ES) of benthos for the Water Framework Directive
(WFD). The indices respond reliably to the impacts of organic enrichment in muddy
sand habitats, but their applicability across a range of pressures and habitats
is less well understood. The ability of the indices to predict changes in
response to pressures in three distinct habitats, intertidal muddy sand, maerl
and inshore gravel, was tested using pre-existing datasets. Both responded
following the same patterns of variation as previously reported. The IQI was more
conservative when responding to environmental conditions so may have greater
predictive value in dynamic habitats to provide an early-warning system to
managers'. Re-calibration of reference conditions is necessary to reliably
reflect ES in different habitats.
PMID- 25127496
TI - Mitochondria, energetics, epigenetics, and cellular responses to stress.
AB - BACKGROUND: Cells respond to environmental stressors through several key
pathways, including response to reactive oxygen species (ROS), nutrient and ATP
sensing, DNA damage response (DDR), and epigenetic alterations. Mitochondria play
a central role in these pathways not only through energetics and ATP production
but also through metabolites generated in the tricarboxylic acid cycle, as well
as mitochondria-nuclear signaling related to mitochondria morphology, biogenesis,
fission/fusion, mitophagy, apoptosis, and epigenetic regulation. OBJECTIVES: We
investigated the concept of bidirectional interactions between mitochondria and
cellular pathways in response to environmental stress with a focus on epigenetic
regulation, and we examined DNA repair and DDR pathways as examples of biological
processes that respond to exogenous insults through changes in homeostasis and
altered mitochondrial function. METHODS: The National Institute of Environmental
Health Sciences sponsored the Workshop on Mitochondria, Energetics, Epigenetics,
Environment, and DNA Damage Response on 25-26 March 2013. Here, we summarize key
points and ideas emerging from this meeting. DISCUSSION: A more comprehensive
understanding of signaling mechanisms (cross-talk) between the mitochondria and
nucleus is central to elucidating the integration of mitochondrial functions with
other cellular response pathways in modulating the effects of environmental
agents. Recent studies have highlighted the importance of mitochondrial functions
in epigenetic regulation and DDR with environmental stress. Development and
application of novel technologies, enhanced experimental models, and a systems
type research approach will help to discern how environmentally induced
mitochondrial dysfunction affects key mechanistic pathways. CONCLUSIONS:
Understanding mitochondria-cell signaling will provide insight into individual
responses to environmental hazards, improving prediction of hazard and
susceptibility to environmental stressors.
PMID- 25127500
TI - Changes in the concentration and relative abundance of alkanes and PAHs from the
Deepwater Horizon oiling of coastal marshes.
AB - We determined changes of 28 alkanes and 43 different PAHs in 418 wetland soil
samples collected on ten sampling trips to three Louisiana estuaries before and
after they were oiled from the 2010 Deepwater Horizon disaster. There was a
significant decline in 22 of the 28 alkane analytes (0.42% day(-1)), no change in
6, over 2.5 years. The concentration of five aromatic petroleum hydrocarbons
(PAHs) increased (range 0.25-0.70% day(-1)), whereas the total PAH pool did not
change. Of these five, naphthalene and C-1-naphthalenes are suggested to be of
higher toxicity than the other three because of their relatively higher
volatility or solubility. The relative proportions of alkane analytes, but not
PAHs, does not yet resemble that in the pre-oiled marshes after 3 years, The
trajectories of nine indicators for degradation/weathering were either
inconclusive or misleading (alkanes) or confirmed the relatively meager
degradation of PAHs.
PMID- 25127501
TI - Floating debris in the Mediterranean Sea.
AB - Results from the first large-scale survey of floating natural (NMD) and
anthropogenic (AMD) debris (>2 cm) in the central and western part of the
Mediterranean Sea are reported. Floating debris was found throughout the entire
study area with densities ranging from 0 to 194.6 items/km(2) and mean abundances
of 24.9 AMD items/km(2) and 6.9 NMD items/km(2) across all surveyed locations. On
the whole, 78% of all sighted objects were of anthropogenic origin, 95.6% of
which were petrochemical derivatives (i.e. plastic and styrofoam). Maximum AMD
densities (>52 items/km(2)) were found in the Adriatic Sea and in the Algerian
basin, while the lowest densities (<6.3 items/km(2)) were observed in the Central
Tyrrhenian and in the Sicilian Sea. All the other areas had mean densities
ranging from 10.9 to 30.7 items/km(2). According to our calculations, more than
62 million macro-litter items are currently floating on the surface of the whole
Mediterranean basin.
PMID- 25127502
TI - Mediterranean diet and risk of frailty in community-dwelling older adults.
AB - BACKGROUND AND OBJECTIVE: Low intake of certain micronutrients and protein has
been associated with higher risk of frailty. However, very few studies have
assessed the effect of global dietary patterns on frailty. This study examined
the association between adherence to the Mediterranean diet (MD) and the risk of
frailty in older adults. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort
study with 1815 community-dwelling individuals aged >=60 years recruited in 2008
2010 in Spain. MEASUREMENTS: At baseline, the degree of MD adherence was measured
with the Mediterranean Diet Adherence Screener (MEDAS) score and the
Mediterranean Diet Score, also known as the Trichopoulou index. In 2012,
individuals were reassessed to detect incident frailty, defined as having at
least 3 of the following criteria: exhaustion, muscle weakness, low physical
activity, slow walking speed, and weight loss. The study associations were
summarized with odds ratios (OR) and their 95% confidence interval (CI) obtained
from logistic regression, with adjustment for the main confounders. RESULTS: Over
a mean follow-up of 3.5 years, 137 persons with incident frailty were identified.
Compared with individuals in the lowest tertile of the MEDAS score (lowest MD
adherence), the OR (95% CI) of frailty was 0.85 (0.54-1.36) in those in the
second tertile, and 0.65 (0.40-1.04; P for trend = .07) in the third tertile.
Corresponding figures for the Mediterranean Diet Score were 0.59 (0.37-0.95) and
0.48 (0.30-0.77; P for trend = .002). Being in the highest tertile of MEDAS was
associated with reduced risk of slow walking (OR 0.53; 95% CI 0.35-0.79) and of
weight loss (OR 0.53; 95% CI 0.36-0.80). Lastly, the risk of frailty was
inversely associated with consumption of fish (OR 0.66; 95% CI 0.45-0.97) and
fruit (OR 0.59; 95% CI 0.39-0.91). CONCLUSIONS: Among community-dwelling older
adults, an increasing adherence to the MD was associated with decreasing risk of
frailty.
PMID- 25127503
TI - A developmental screening tool for toddlers with multiple domains based on Rasch
analysis.
AB - BACKGROUND/PURPOSE: Using multidomain developmental screening tools is a feasible
method for pediatric health care professionals to identify children at risk of
developmental problems in multiple domains simultaneously. The purpose of this
study was to develop a Rasch-based tool for Multidimensional Screening in Child
Development (MuSiC) for children aged 0-3 years. METHODS: The MuSic was developed
by constructing items bank based on three commonly used screening tools,
validating with developmental status (at risk for delay or not) on five
developmental domains. Parents of a convenient sample of 632 children (aged 3
35.5 months) with and without developmental delays responded to items from the
three screening tools funded by health authorities in Taiwan. Item bank was
determined by item fit of Rasch analysis for each of the five developmental
domains (cognitive skills, language skills, gross motor skills, fine motor
skills, and socioadaptive skills). Children's performance scores in logits
derived in Rasch analysis were validated with developmental status for each
domain using the area under receiver operating characteristic curves. RESULTS:
MuSiC, a 75-item developmental screening tool for five domains, was derived. The
diagnostic validity of all five domains was acceptable for all stages of
development, except for the infant stage (<=11 months and 15 days). CONCLUSION:
MuSiC can be applied simultaneously to well-child care visits as a universal
screening tool for children aged 1-3 years on multiple domains. Items with sound
validity for infants need to be further developed.
PMID- 25127504
TI - Impact of guideline changes on use or omission of radiation in the elderly with
early breast cancer: practice patterns at National Comprehensive Cancer Network
institutions.
AB - BACKGROUND: Breast radiation therapy (RT) is a care standard after breast
conservation surgery that improves local control and survival in women. In 2004,
a phase III trial demonstrated radiation after breast-conservation surgery
provided no survival and limited local control benefit to women aged 70 years and
older with stage I, estrogen receptor-positive cancers who receive endocrine
therapy. This led to breast-conservation surgery and endocrine therapy alone
being incorporated as a category I option in the National Comprehensive Cancer
Network (NCCN) Guidelines for older women in 2004. We examined factors associated
with change in radiation use in elderly patients at 13 NCCN centers. STUDY
DESIGN: We identified women treated at NCCN centers meeting age and stage
criteria during 2000 to 2009. Factors considered a priori potentially associated
with RT use were evaluated in univariate and multivariable models, including year
of diagnosis, tumor and patient characteristics, axillary surgery, and treating
institution. Date of diagnosis was classified as 2000 to 2004 vs 2005 to 2009,
reflecting when guidelines changed. RESULTS: Among 1,292 eligible cases, 78%
received RT. In multivariable analysis, diagnosis after 2004 (p = 0.0003), older
age (p < 0.0001), higher comorbidity score (p = 0.0006), smaller tumors (p =
0.0146), and omission of axillary surgery (p < 0.0001) predicted RT omission.
Ninety-four percent of women aged 70 to 74 years received RT in 2000, compared
with 88% in 2009. For the same times and age 80 years and older, RT use was 80%
vs 41%. Finally, RT use was associated with treating institution (p < 0.0001).
CONCLUSIONS: After guideline changes for RT use in older women, NCCN centers
demonstrated wide variation in implementing change. This suggests other factors
are also influencing guideline uptake.
PMID- 25127505
TI - Modified rendezvous biliary procedure involving the hepatobiliary surgeon,
endoscopist, and interventional radiologist: a novel solution for complex bile
duct injuries.
PMID- 25127506
TI - Reoperative complications after primary orthotopic liver transplantation: a
contemporary single-center experience in the post-model for end-stage liver
disease era.
AB - BACKGROUND: Data on complications requiring reoperation after orthotopic liver
transplantation (OLT) are limited. We sought to describe the spectrum of
reoperative complications after OLT, evaluate the associations with graft and
patient survival, and identify predictors of need for reoperation. STUDY DESIGN:
We retrospectively studied adult patients who underwent primary OLT at our
institution from February 2002 to July 2012. The primary outcomes included
occurrence of a reoperative complication. Secondary outcomes were graft and
patient survival. Multivariable logistic regression analysis was used to model
the associations of recipient, donor, and operative variables with reoperation.
RESULTS: Of 1,620 patients, 470 (29%) had complications requiring reoperation.
The most common reoperative complication was bleeding (17.3%). Compared with
patients not requiring reoperation, patients with reoperative complications had
greater Model for End-Stage Liver Disease scores and need for pretransplantation
hospitalization, mechanical ventilation, vasopressors, and renal replacement
therapy; considerably longer cold and warm ischemia times and greater
intraoperative blood transfusion requirements; and substantially worse 1-, 3-,
and 5-year graft and patient survival rates. In multivariable analysis,
predictors of reoperative complications included intraoperative transfusion of
packed RBCs (odds ratio [OR] = 2.21; 95% CI, 1.91-2.56), donor length of
hospitalization >8 days (OR = 1.87; 95% CI, 1.28-2.73), recipient
pretransplantation mechanical ventilation (OR = 1.65; 95% CI, 1.21-2.24), cold
ischemia time >9 hours (OR = 1.63; 95% CI, 1.23-2.17), warm ischemia time >55
minutes (OR = 1.58; 95% CI, 1.02-2.44), earlier major abdominal surgery (OR =
1.41; 95% CI, 1.03-1.92), and elevated donor serum sodium (OR = 1.17; 95% CI,
1.03-1.31). CONCLUSIONS: Patients who require reoperation for complications after
OLT have high pretransplantation acuity and inferior post-transplantation
survival. We identified factors associated with reoperative complications to
guide perioperative donor-recipient matching and improve outcomes.
PMID- 25127507
TI - Median arcuate ligament release.
PMID- 25127508
TI - Practical management of postoperative atrial fibrillation after noncardiac
surgery.
PMID- 25127509
TI - Automated quantitative analysis of tissue microarray of 443 patients with
colorectal adenocarcinoma: low expression of Bcl-2 predicts poor survival.
AB - BACKGROUND: Bcl-2 has been implicated in the development and progression of a
number of cancers including colorectal cancer. Reports of Bcl-2 expression in
colorectal cancer and patient outcomes have been inconsistent due to small
cohorts and semi-quantitative grading methods. STUDY DESIGN: We used a high
throughput tissue microarray system (automated quantitative analysis [AQUA]),
analyzing colorectal adenocarcinoma samples from 443 patients resected during the
period of 1967 to 1986. This system uses fully quantitative, automated
fluorescent microscopy to accurately assess Bcl-2 expression in colorectal cancer
samples. Clinicopathologic variables were collected prospectively and were
assessed using log-rank tests and Cox proportional hazards models. RESULTS: At a
median follow-up of 54 months, the 5- and 10-year disease-specific survivals for
all patients were 59.2% and 52.1%, respectively. Loss of Bcl-2 expression was
seen in 70.4% of tumors and was associated with a decreased 5-year disease
specific survival (55.8% vs 75.6%, p = 0.001 and relative risk [RR] 1.8) and
decreased 5-year overall survival (45.8% vs 56.5%, p = 0.046 and RR 1.2). On
univariate analysis, T stage, N stage, and loss of Bcl-2 expression predicted
poor disease-specific survival. On multivariate analysis, Bcl-2 expression was an
independent prognostic factor for disease-specific survival (p = 0.034).
CONCLUSIONS: Our results indicate that loss of Bcl-2 expression in colorectal
cancer is associated with decreased disease-specific and overall survival. This
finding may help identify a subset of patients with a more aggressive phenotype
and guide adjuvant chemotherapy choices.
PMID- 25127510
TI - Isolated free fluid on abdominal computed tomography in blunt trauma: watch and
wait or operate?
AB - BACKGROUND: Isolated free fluid (FF) on abdominal CT in stable blunt trauma
patients can indicate the presence of hollow viscus injury. No criteria exist to
differentiate treatment by operative exploration vs observation. The goals of
this study were to determine the incidence of isolated FF and to identify factors
that discriminate between patients who should undergo operative exploration vs
observation. STUDY DESIGN: A review of blunt trauma patients at a Level I trauma
center from July 2009 to March 2012 was performed. Patients with a CT showing
isolated FF after blunt trauma were included. Data collected included
demographics, injury severity, physical examination, CT, and operative findings.
RESULTS: Two thousand eight hundred and ninety-nine patients had CT scans, 156
(5.4%) of whom had isolated FF. The therapeutic operative group included 13
patients; 9 had immediate operation and 4 failed nonoperative management. The
nonoperative/nontherapeutic operation group consisted of 142 patients with
successful nonoperative management and 1 patient with a nontherapeutic operation.
Abdominal tenderness was documented in 69% of the therapeutic operative group and
23% of the nonoperative/nontherapeutic group (odds ratio = 7.5; p < 0.001). The
presence of a moderate to large amount of FF was increased in the therapeutic
operative group (85% vs 8%; odds ratio = 66; p < 0.001). CONCLUSIONS: Isolated FF
was noted in 5.4% of stable blunt trauma patients. Blunt trauma patients with
moderate to large amounts of FF without solid organ injury on CT and abdominal
tenderness should undergo immediate operative exploration. Patients with neither
of these findings can be safely observed.
PMID- 25127511
TI - Long-term health-related quality of life after iatrogenic bile duct injury
repair.
AB - BACKGROUND: Data on the effect of bile duct injuries (BDI) on health-related
quality of life (HRQOL) are not well defined. We sought to assess long-term HRQOL
after BDI repair in a large cohort of patients spanning a 23-year period. STUDY
DESIGN: We identified and mailed HRQOL questionnaires to all patients treated for
major BDI after laparoscopic cholecystectomy between January 1, 1990 and December
31, 2012 at Johns Hopkins Hospital. RESULTS: We identified 167 patients alive at
the time of the study who met the inclusion criteria. Median age at BDI was 42
years (interquartile range 31 to 54 years); the majority of patients were female
(n = 131 [78.4%]) and of white race (n = 137 [83.0%]). Most patients had Bismuth
level 2 (n = 56 [33.7%]) or Bismuth level 3 (n = 40 [24.1%]) BDI. Surgical repair
most commonly involved a Roux-en-Y hepaticojejunostomy (n = 142 [86.1%]). Sixty
two patients (37.1%) responded to the HRQOL questionnaire. Median follow-up was
169 months (interquartile range 125 to 222 months). At the time of BDI, mental
health was most affected, with patients commonly reporting a depressed mood
(49.2%) or low energy level (40.0%). These symptoms improved significantly after
definitive repair (both p < 0.05). Limitations in physical activity and general
health remained unchanged before and after surgical repair (both p > 0.05).
CONCLUSIONS: Mental health concerns were more commonplace vs physical or general
health issues among patients with BDI followed long term. Optimal
multidisciplinary management of BDI can help restore HRQOL to preinjury levels.
PMID- 25127514
TI - The effects of a modified spinal mobilisation with leg movement (SMWLM) technique
on sympathetic outflow to the lower limbs.
AB - Physiotherapy management of lumbar disorders, based on Mulligan's mobilization
techniques, is a treatment of choice by many physiotherapists, however, there is
only limited evidence of any neurophysiological effects and much of this has
focused on the cervical spine and upper limbs. This study aims to extend the
knowledge base underpinning the use of a modified Mulligan's spinal mobilisation
with leg movement technique (SMWLM) by exploring its effects on the peripheral
sympathetic nervous system (SNS) of the lower limbs. Using a single blind,
placebo controlled, independent groups study design, 45 normal naive healthy
males were randomly assigned to one of three experimental groups (control,
placebo or treatment; SMWLM). SNS activity was determined by recording skin
conductance (SC) obtained from lower limb electrodes connected to a BioPac unit.
Validation of the placebo technique was performed by post- intervention
questionnaire. Results indicated that there was a significant change in SC from
baseline levels (30%) that was specific to the side treated for the treatment
group during the intervention period (compared to placebo and control
conditions). This study provides preliminary evidence that a modified SMWLM
technique results in side-specific peripheral SNS changes in the lower limbs.
PMID- 25127512
TI - The innate immune sensor LGP2 activates antiviral signaling by regulating MDA5
RNA interaction and filament assembly.
AB - Cytoplasmic pattern recognition receptors detect non-self RNAs during virus
infections and initiate antiviral signaling. One receptor, MDA5, possesses
essential signaling domains, but weak RNA binding. A second receptor, LGP2,
rapidly detects diverse dsRNA species, but lacks signaling domains. Accumulating
evidence suggests LGP2 and MDA5 work together to detect viral RNA and generate a
complete antiviral response, but the basis for their cooperation has been
elusive. Experiments presented here address this gap in antiviral signaling,
revealing that LGP2 assists MDA5-RNA interactions leading to enhanced MDA5
mediated antiviral signaling. LGP2 increases the initial rate of MDA5-RNA
interaction and regulates MDA5 filament assembly, resulting in the formation of
more numerous, shorter MDA5 filaments that are shown to generate equivalent or
greater signaling activity in vivo than the longer filaments containing only
MDA5. These findings provide a mechanism for LGP2 coactivation of MDA5 and a
biological context for MDA5-RNA filaments in antiviral responses.
PMID- 25127513
TI - Lysine acetylation controls local protein conformation by influencing proline
isomerization.
AB - Gene transcription responds to stress and metabolic signals to optimize growth
and survival. Histone H3 (H3) lysine 4 trimethylation (K4me3) facilitates state
changes, but how levels are coordinated with the environment is unclear. Here, we
show that isomerization of H3 at the alanine 15-proline 16 (A15-P16) peptide bond
is influenced by lysine 14 (K14) and controls gene-specific K4me3 by balancing
the actions of Jhd2, the K4me3 demethylase, and Spp1, a subunit of the Set1 K4
methyltransferase complex. Acetylation at K14 favors the A15-P16trans
conformation and reduces K4me3. Environmental stress-induced genes are most
sensitive to the changes at K14 influencing H3 tail conformation and K4me3. By
contrast, ribosomal protein genes maintain K4me3, required for their repression
during stress, independently of Spp1, K14, and P16. Thus, the plasticity in
control of K4me3, via signaling to K14 and isomerization at P16, informs distinct
gene regulatory mechanisms and processes involving K4me3.
PMID- 25127515
TI - [11C]NS8880, a promising PET radiotracer targeting the norepinephrine
transporter.
AB - INTRODUCTION: Positron emission tomography (PET) imaging of the norepinephrine
transporter (NET) is still hindered by the availability of useful PET imaging
probes. The present study describes the radiosynthesis and pre-clinical
evaluation of a new compound, exo-3-(6-methoxypyridin-2-yloxy)-8-H-8
azabicyclo[3.2.1]octane (NS8880), targeting NET. NS8880 has an in vitro binding
profile comparable to desipramine and is structurally not related to reboxetine.
METHODS: Labeling of NS8880 with [(11)C] was achieved by a non-conventional
technique: substitution of pyridinyl fluorine with [(11)C]methanolate in a Boc
protected precursor. The isolated [(11)C]NS8880 was evaluated pre-clinically both
in a pig model (PET scanning) and in a rat model (MUPET scanning) and compared to
(S,S)-[(11)C]-O-methylreboxetine ([(11)C]MeNER). RESULTS: The radiolabeling
technique yielded [(11)C]NS8880 in low (<10%) but still useful yields with high
purity. The PET in vivo evaluation in pig and rat revealed a rapid brain uptake
of [(11)C]NS8880 and fast obtaining of equilibrium. Highest binding was observed
in thalamic and hypothalamic regions. Pretreatment with desipramine efficiently
reduced binding of [(11)C]NS8880. CONCLUSION: Based on the pre-clinical results
obtained so far [(11)C]NS8880 displays promising properties for PET imaging of
NET.
PMID- 25127516
TI - Theory of dynamical electron channeling contrast images of near-surface crystal
defects.
AB - This paper describes the dynamical simulation of electron channeling contrast
images (ECCIs) of dislocations. The approach utilizes both the Bloch wave
formalism and the scattering matrix formalism to generate electron channeling
patterns (ECPs). The latter formalism is then adapted to include the effect of
lattice defects on the back-scattered electron yield, resulting in a
computational algorithm for the simulation of ECCIs. Dislocations of known line
direction and Burgers vector are imaged experimentally by ECCI and match well
with simulated ECCIs for various channeling conditions. Experiment/simulation
comparisons for ECPs and ECCIs are demonstrated for metals (Al), semiconductors
(Si), and ceramics (SrTiO3).
PMID- 25127517
TI - Effect of surface stress on microcantilever resonance frequency during water
adsorption: influence of microcantilever dimensions.
AB - This paper reports the effect of dimensions of microcantilever (MC) on its
resonance frequency and bending upon adsorption of water molecules. Study is
conducted on three MCs having the dimensions of 450 * 40 * 2.5 MUm(3) (MC1), 225
* 30 * 3 MUm(3) (MC2) and 125 * 35 * 4.5 MUm(3) (MC3). The measured resonant
frequency showed the expected negative shift in MC1, initially positive followed
by a negative shift in MC2 and only positive shift in MC3 during adsorption. This
behavior is attributed to changes in the stiffness of the MC associated with the
surface stress. The surface stress generated on the MC has been derived from its
bending measurements upon water adsorption. The change in the stiffness of MC
evaluated from an independent estimate of expected frequency shift showed that
the relative stiffness change of MC increases linearly with the surface stress
scaled with cube of width to height ratio of MCs, confirming the dimensional
dependence of adsorption induced stiffness change.
PMID- 25127518
TI - Validation and application of an UPLC-MS/MS method for the quantification of
synthetic cannabinoids in urine samples and analysis of seized materials from the
Portuguese market.
AB - An UPLC-MS/MS method using ESI+ionization and MRM was developed and fully
validated according to international guidelines for the qualitative and
quantitative analysis of nine synthetic cannabinoids and/or their metabolites in
urine samples (1mL). Prior to extraction the samples were subjected to an
enzymatic hydrolysis using beta-glucuronidase followed by a SPE procedure using
Oasis((r)) HLB 3cc (60mg) columns. The chromatographic separation was performed
with an Acquity UPLC((r)) HSS T3 (50mm*2.1mm i.d., 1.8MUm) reversed-phase column
using a gradient with methanol-ammonium formate 2mM (0.1% formic acid) and with a
run time of 9.5min. The method was validated in terms of selectivity, capacity of
identification, limits of detection (0.01-0.5ng/mL) and quantification (0.05
0.5ng/mL), recovery (58-105%), carryover, matrix effect, linearity (0.05
50ng/mL), intra-assay precision, inter-assay accuracy and precision (CV<20%). The
method was applied to 80 authentic samples, five of them (6.2%) were confirmed or
suspected to be positive for the metabolites JWH-018 N-hydroxypentyl and JWH-018
N-pentanoic acid of JWH-018 and for the metabolite JWH-122 N-(5-hydroxypentyl) of
JWH-122, and three of them in association with THC and/or THCCOOH (substances
included in the method, together with the 11-OH-THC). Additionally, 17 spice
products were analyzed, for which were confirmed the presence of the following
substances: AM-2201, JWH-018, JWH-022 JWH-073, JWH-122, JWH-203, JWH-210, JWH
250, HU-210 and RCS-4, according to the comparison with authentic reference
material and published data. The analytical method developed allowed the analysis
of synthetic cannabinoids and the notification of the first cases in Portugal.
PMID- 25127519
TI - Accident rates amongst regular bicycle riders in Tasmania, Australia.
AB - PURPOSE: To characterise the demographics, cycling habits and accident rates of
adult cyclists in Tasmania. METHODS: Volunteers >=18 years of age who had cycled
at least once/week over the previous month provided information on demographics;
cycling experience; bicycles owned; hours/km/trips cycled per week; cycling
purpose; protective equipment used; and major (required third-party medical
treatment or resulted >=1 day off work) or minor (interfered with individuals'
regular daily activities and/or caused financial costs) accidents while cycling.
RESULTS: Over 8-months, 136 cyclists (70.6% male) completed the telephone survey.
Mean (standard deviation) age was 45.4 (12.1) years with 17.1 (11.4) years of
cycling experience. In the week prior to interview, cyclists averaged 6.6
trips/week (totalling 105.7km or 5.0h). The most common reason for cycling was
commuting/transport (34% of trips), followed by training/health/fitness (28%).
The incidence of major and minor cycling accidents was 1.6 (95% CI 1.1-2.0) and
3.7 (2.3-5.0) per 100,000km, respectively. Male sex was associated with a
significantly lower minor accident risk (incidence rate ratio=0.34, p=0.01).
Mountain biking was associated with a significantly higher risk of minor accident
compared with road or racing, touring, and city or commuting biking (p<0.05).
CONCLUSIONS: Physical activity of regular cyclists' exceeds the level recommended
for maintenance of health and wellbeing; cyclists also contributed substantially
to the local economy. Accident rates are higher in this sample than previously
reported in Tasmania and internationally. Mountain biking was associated with
higher risks of both major and minor accidents compared to road/racing bike
riding.
PMID- 25127520
TI - Is air quality index associated with cardiometabolic risk factors in adolescents?
The CASPIAN-III Study.
AB - OBJECTIVE: This study aims to evaluate the association of air quality index (AQI)
with cardiometabolic risk factors in a nationally representative sample of
healthy adolescents. METHODS: This nationwide survey was conducted among a
stratified multi-stage probability sample of students, aged 10-18 years, from 27
provinces of Iran. Those students with history of any acute or chronic diseases,
any medication use, as well as active or passive smoking were not included to the
current study. Dietary and physical activity habits were documented by valid
questionnaires. Physical examination and blood sampling were conducted under
standard protocols. AQI data were obtained from air pollution monitoring sites
from the entire country by considering air pollutants concentration, which
includes all provincial counties containing different clusters. RESULTS: The
study participants consisted of 1413 students (48.8% boys) with a mean (SD) age
of 14.81+/-2.48 years. The mean AQI level was 285.37+/-30.11 at national levels.
After adjustment for confounding factors including age, sex, and anthropometric
measures, as well as for dietary and physical activity habits, multiple linear
regressions based on correlation of coefficients of the AQI with cardiometabolic
risk factors showed significant positive correlations of AQI with systolic blood
pressure, fasting blood glucose, total cholesterol, LDL-cholesterol, and
triglycerides, as well as significant negative correlations with HDL-cholesterol.
After adjustment for abovementioned confounding factors, binary logistic
regressions analyses showed that AQI increased the risk of abnormal levels of
some risk factors as elevated levels of systolic blood pressure, total
cholesterol, and triglycerides. CONCLUSION: The associations of low air quality
with some cardiometabolic factors in the current survey, although not strong,
might be considered as an evidence of the adverse cardiometabolic consequences of
exposure to air pollutants in the pediatric age group, and predisposing them to
earlier development of non-communicable diseases.
PMID- 25127521
TI - Determinants of bisphenol A and phthalate metabolites in urine of Flemish
adolescents.
AB - As part of the second Flemish Environment and Health Study (FLEHS II), bisphenol
A (BPA) and different phthalate metabolites were analyzed, for the first time, in
the urine of 210 adolescents in Flanders, Belgium. All chemicals had a detection
frequency above 90%. For all compounds, except the sum of DEHP, highest levels
were detected during spring. Average values for the Flemish adolescents were in
an agreement with concentrations found in different international studies, all
confirming the ubiquity of BPA and phthalate exposure. There was a significant
correlation between BPA and the different phthalate metabolites (r between 0.26
and 0.39; p<0.01). Shared sources of exposure to BPA and phthalates, such as food
packaging, were suggested to be responsible for this positive correlation.
Different determinants of exposure were evaluated in relation to the urinary
concentrations of these chemicals. For BPA, a significant association was
observed with household income class, smoking and exposure to environmental
tobacco smoke. For phthalates, the following significant associations were
observed: age (MBzP), educational level of the adolescent (MBzP), equivalent
household income (MnBP), use of personal care products (MnBP and MBzP), wall
paper in house (MnBP and MBzP) and use of local vegetables (MnBP and MBzP).
PMID- 25127522
TI - A new and sensitive method for measuring in vivo and in vitro cytotoxicity in
earthworm coelomocytes by flow cytometry.
AB - This study describes a new and sensitive method for measuring the in vivo and in
vitro cytotoxicity of 2 earthworm species, Eisenia andrei and Perionyx excavatus,
exposed to copper. Specifically, we measured the number of coelomocyte cells that
were affected by copper following in vivo and in vitro exposure by flow
cytometry, after calcein acetoxymethyl ester (calcein-AM) staining. We found that
the coelomocyte viability of both earthworm species was noticeably reduced in the
in vivo cytotoxicity test at concentrations of 100mg/kg copper in dry soil.
However, pathological symptoms, such as mucous secretion and bleeding, swelling,
thinning, and fragmentation, and burrowing symptoms were not evident following
exposure to copper levels of <400mg/kg dry soil. In conclusion, the present study
demonstrates that calcein-AM is a more sensitive test of earthworm coelomocyte
cytotoxicity compared to the traditional individual level toxicity test.
Therefore, this test could be used to detect low levels of metal contamination in
soils.
PMID- 25127523
TI - Temperature-related mortality in 17 large Chinese cities: how heat and cold
affect mortality in China.
AB - Few multicity studies have been conducted to investigate the acute health effects
of cold and hot temperatures in China. We aimed to examine the relationship
between temperature and daily mortality in 17 large Chinese cities. We first
calculated city-specific effect of temperature using time-series regression
models combined with distributed lag nonlinear models; then we pooled the city
specific estimates with the Bayesian hierarchical models. The cold effects lasted
longer than the hot effects. For the cold effects, a 1 degrees C decrease from
the 25th to 1st percentiles of temperature over lags 0-14 days was associated
with increases of 1.69% [95% posterior intervals (PI): 1.01%, 2.36%], 2.49% (95%
PI: 1.53%, 3.46%) and 1.60% (95% PI: 0.32%, 2.87%) in total, cardiovascular and
respiratory mortality, respectively. For the hot effects, a 1 degrees C increase
from the 75th to 99th percentiles of temperature was associated with
corresponding increases of 2.83% (95% PI: 1.42%, 4.24%), 3.02% (95% PI: 1.33%,
4.71%) and 4.64% (95% PI: 1.96%, 7.31%). The latitudes, number of air
conditioning per household and disposable income per capita were significant
modifiers for cold effects; the proportion of the elderly was a significant
modifier for hot effects. This largest epidemiological study of temperature to
date in China suggested that both cold and hot temperatures were associated with
increased mortality. Our findings may have important implications for the public
health policies in China.
PMID- 25127524
TI - Temporal trends of radio-frequency electromagnetic field (RF-EMF) exposure in
everyday environments across European cities.
AB - BACKGROUND: The rapid development and increased use of wireless telecommunication
technologies led to a substantial change of radio-frequency electromagnetic field
(RF-EMF) exposure in the general population but little is known about temporal
trends of RF-EMF in our everyday environment. OBJECTIVES: The objective of our
study is to evaluate temporal trends of RF-EMF exposure levels in different
microenvironments of three European cities using a common measurement protocol.
METHODS: We performed measurements in the cities of Basel (Switzerland), Ghent
and Brussels (Belgium) during one year, between April 2011 and March 2012. RF-EMF
exposure in 11 different frequency bands ranging from FM (Frequency Modulation,
88 MHz) to WLAN (Wireless Local Area Network, 2.5 GHz) was quantified with
portable measurement devices (exposimeters) in various microenvironments: outdoor
areas (residential areas, downtown and suburb), public transports (train, bus and
tram or metro rides) and indoor places (airport, railway station and shopping
centers). Measurements were collected every 4s during 10-50 min per environment
and measurement day. Linear temporal trends were analyzed by mixed linear
regression models. RESULTS: Highest total RF-EMF exposure levels occurred in
public transports (all public transports combined) with arithmetic mean values of
0.84 V/m in Brussels, 0.72 V/m in Ghent, and 0.59 V/m in Basel. In all outdoor
areas combined, mean exposure levels were 0.41 V/m in Brussels, 0.31 V/m in Ghent
and 0.26 V/m in Basel. Within one year, total RF-EMF exposure levels in all
outdoor areas in combination increased by 57.1% (p<0.001) in Basel by 20.1% in
Ghent (p=0.053) and by 38.2% (p=0.012) in Brussels. Exposure increase was most
consistently observed in outdoor areas due to emissions from mobile phone base
stations. In public transports RF-EMF levels tended also to increase but mostly
without statistical significance. DISCUSSION: An increase of RF-EMF exposure
levels has been observed between April 2011 and March 2012 in various
microenvironments of three European cities. Nevertheless, exposure levels were
still far below regulatory limits of each country. A continuous monitoring is
needed to identify high exposure areas and to anticipate critical development of
RF-EMF exposure at public places.
PMID- 25127525
TI - Nonylphenol in pregnant women and their matching fetuses: placental transfer and
potential risks of infants.
AB - As the predominant environmental biodegradation product of nonylphenol (NP)
ethoxylates and with proven estrogenic effects, NP is formed during the
alkylation process of phenols. The purposes of this study were (1) to examine
maternal and prenatal exposure to NP in Taiwan, (2) to determine the level of
placental protection against NP exposure as well as the level of NP in breast
milk, and (3) to assess the potential risk for breastfed newborns exposed to NP
through the milk. Thirty pairs of maternal and fetal blood samples, placenta, and
breast milk during the 1st and the 3rd months of lactation were collected.
External NP exposures of these specimens were then analyzed by using high
performance liquid chromatography coupling with fluorescence detection. Next, the
socio-demographics, lifestyle, delivery method, dietary and work history were
collected using a questionnaire. In addition, the daily intake of NP from
consuming breast milk in the 1st and 3rd months for newborns was studied through
deterministic and probabilistic risk assessment methods. The geometric means and
geometric standard deviation of NP levels in maternal blood, fetal cord blood,
placenta, and breast milk in the 1st and 3rd months were 14.6 (1.7) ng/ml, 18.8
(1.8) ng/ml, 19.8 (1.9) ng/g, 23.5 (3.2) ng/ml, and 57.3 (1.4) ng/ml,
respectively. The probabilistic percentiles (50th, 75th, and 95th) of daily
intake NP in breast milk were 4.33, 7.79, and 18.39 MUg/kg-bw/day in the 1st
month, respectively, and were 8.11, 10.78, 16.08 MUg/kg-bw/day in the 3rd month,
respectively. The probabilistic distributions (5th, 25th, and 50th) of risk for
infants aged 1 month old were 0.27, 0.64, and 1.15, respectively, and that for
infants aged 3 month old were 0.31, 0.46, and 0.62, respectively. Through
repeated exposure from the dietary intake of expectant mothers, fetuses could
encounter a high NP exposure level due to transplacental absorption, partitioning
between the maternal and fetal compartments. Daily NP intake via breast milk in
three month-old babies exceeded the tolerable daily intake (TDI) of 5 ug/kg
bw/day indicated a potential risk for Taiwan infants.
PMID- 25127526
TI - A computed tomography evaluation of two hundred normal ankles, to ascertain what
anatomical landmarks to use when compressing or placing an ankle syndesmosis
screw.
AB - Classical AO teaching recommends that a syndesmosis screw should be inserted at
25-30 degrees to the coronal plane of the ankle. Accurately judging the 25/30
degree angle can be difficult, resulting in poor operative reduction of
syndesmosis injuries. The CT scans of 200 normal ankles were retrospectively
examined. The centroid of the fibula and tibia in the axial plane 15mm proximal
to the talar dome was calculated. A force vector between the centroid of the
fibula and the tibia in the axial plane should not displace the fibula relative
to the tibia when surfaces are parallel. Therefore, a line connecting the two
centroids was postulated to be the ideal syndesmosis line. This line was shown to
pass through the fibula within 2.5mm of the lateral cortical apex of the fibula
and the anterior half of the medial malleolus in 100% of the ankles studied. The
results support the concept that in the operatively reduced syndesmosis, the
anterior half of the medial malleolus can be used as a reliable guide for aiming
the syndesmosis drill hole, provided that the fibular entry point is at/or
adjacent to the lateral fibular apex. The screw should also remain parallel to
the tibial plafond in the coronal plane.
PMID- 25127527
TI - Intracellular Haemophilus influenzae invades the brain: is zyxin a critical blood
brain barrier component regulated by TNF-alpha?
PMID- 25127528
TI - Polyphosphate-mediated modulation of Campylobacter jejuni biofilm growth and
stability.
AB - Biofilms increase C. jejuni's resilience to detergents, antibiotics, and
environmental stressors. In these investigations, we studied the modulation of
biofilm in response to phosphate related stressors. We found that the deletion of
ppk1, phoX, and ppk2 (polyphosphate associated [poly P] genes) in C. jejuni
modulated different stages of biofilm formation such as attached microcolonies,
air-liquid biofilms, and biofilm shedding. Additionally, inorganic phosphate also
modulated attached microcolonies, air-liquid biofilms, and biofilm shedding both
independently of and additively in the poly P associated mutants. Furthermore, we
observed that these different biofilm stages were affected by biofilm age: for
example, the adherent microcolonies were maximum on day 2, while biofilm growth
at the air-liquid interface and shedding was highest on day 3. Also, we observed
altered calcofluor white reactive polysaccharides in poly P-associated mutants,
as well as increased secretion of autoinducer-2 (AI-2) quorum sensing molecules
in the ?ppk2 mutant. Further, the polysaccharide and flagellar biosynthesis
genes, that are associated with biofilm formation, were altered in these poly P
associated mutants. We conclude that the phosphate limiting condition modulates
C. jejuni biofilm formation.
PMID- 25127529
TI - Cardiorespiratory fitness and cardiovascular burden in chronic kidney disease.
AB - OBJECTIVES: Reduced functional capacity is associated with poor prognosis. In
patients with chronic kidney disease the factors that contribute to low
cardiorespiratory fitness are unclear. The objective of this study was to
evaluate the cardiorespiratory and cardiovascular response to exercise in chronic
kidney disease patients, and secondly investigate the relationships between
cardiorespiratory fitness and cardiovascular burden. DESIGN: Cross-sectional
analysis. METHODS: Baseline demographic, anthropometric and biochemical data were
examined in 136 patients with moderate chronic kidney disease (age 59.7+/-9.6yrs,
eGFR 40+/-9ml/min/1.73m(2), 55% male, 39% with a history of cardiovascular
disease, 38% diabetic and 17% current smokers). Cardiorespiratory fitness was
measured as peak VO2, left ventricular morphology and function using
echocardiography, central arterial stiffness by aortic pulse wave velocity and
left ventricular afterload using augmentation index. Physical activity levels
were assessed using the Active Australia questionnaire. RESULTS: Peak VO2 (22.9+/
6.5ml/kg/min) and peak heart rate (148+/-22bpm) were 17% and 12% lower than the
age-predicted values, respectively. The low fit group were significantly older,
and were more likely to have type II diabetes, cardiovascular disease, a higher
BMI and be less active than the high fit group (P<0.05). The independent
predictors of peak VO2 were age, type II diabetes, hemoglobin level, physical
activity, aortic pulse wave velocity, augmentation index, and global longitudinal
strain. CONCLUSIONS: In patients with chronic kidney disease, the peak VO2 and
heart rate response is markedly impaired. Reduced cardiorespiratory fitness is
independently associated with increased aortic stiffness, increased left
ventricle afterload, poor left ventricle function and higher burden of
cardiovascular risk.
PMID- 25127530
TI - Effects of femoral rotational taping on pain, lower extremity kinematics, and
muscle activation in female patients with patellofemoral pain.
AB - OBJECTIVES: To explore the hip and knee joint kinematics as well as muscle
activation between participants with patellofemoral pain syndrome (PFPS) and
controls, and to investigate the immediate effect of proximal femoral rotational
taping on pain, joint kinematics, and muscle activation during single-leg squat
(SLS). DESIGN: Cross-sectional study. METHODS: Sixteen female participants with
PFPS, and eight healthy female controls participated. Three-dimensional hip and
patellar kinematics measured by electromagnetic tracking system, hip (gluteus
maximus and gluteus medius) and thigh (rectus femoris) muscle activation measured
by EMG, and subjective report of pain were recorded during SLS in three
randomized conditions of no tape, sham taping, and femoral rotational taping with
kinesiotape. RESULTS: Without taping, compared with controls, PFPS group had
increased hip adduction angle (23.5+/-11.3 degrees vs. 15.8+/-7.3 degrees )
during SLS. Additionally, PFPS group exhibited lesser rectus femoris activity
during the initial 0-15 degrees of SLS. Application of both femoral rotational
and sham tapes reduced pain for PFPS group. Compared with no tape or sham tape,
femoral rotational tape significantly shifted the patella into more posterior
(1.59+/-0.83cm in no tape vs. 1.54+/-0.87cm in sham tape vs. 1.32+/-0.72cm in
femoral rotational tape) and distal (-2.49+/-0.95cm vs. -2.64+/-0.80cm vs.
3.11+/-0.77cm) positions in the PFPS group. CONCLUSIONS: Femoral rotational
taping could alter patellofemoral kinematics and decrease pain in treatment of
young female participants with PFPS.
PMID- 25127532
TI - Traumatic lens subluxation presenting as pseudomelanoma.
AB - An 82-year-old white man was referred for a suspected inferior pigmented,
choroidal melanoma in his left eye. The patient stated that his left eye had been
hit by a tree branch approximately 40 years prior, and he had not been able to
see with it since then. Dilated fundus examination revealed a 14 * 8 mm dark,
dome-shaped choroidal mass located inferiorly. Transillumination of the eye
revealed no defects. Ultrasonography revealed a hollow lesion, consistent with a
senile, dark dislocated cataract.
PMID- 25127534
TI - Immigrant and refugee health: foreward.
PMID- 25127531
TI - Aberrant hetero-disulfide bond formation by the hypertriglyceridemia-associated
p.Gly185Cys APOA5 variant (rs2075291).
AB - OBJECTIVE: Apolipoprotein A-V (apoA-V) is a low-abundance plasma protein that
modulates triacylglycerol homeostasis. Gene transfer studies were undertaken in
apoa5 (-/-) mice to define the mechanism underlying the correlation between the
single-nucleotide polymorphism c.553G>T in APOA5 and hypertriglyceridemia.
APPROACH AND RESULTS: Adeno-associated virus (AAV) 2/8-mediated gene transfer of
wild-type apoA-V induced a dramatic lowering of plasma triacylglycerol in apoa5 (
/-) mice, whereas AAV2/8-Gly162Cys apoA-V (corresponding to the c.553G>T single
nucleotide polymorphism: rs2075291; p.Gly185Cys when numbering includes signal
sequence) had a modest effect. Characterization studies revealed that plasma
levels of wild-type and G162C apoA-V in transduced mice were similar and within
the physiological range. Fractionation of plasma from mice transduced with AAV2/8
G162C apoA-V indicated that, unlike wild-type apoA-V, >50% of G162C apoA-V was
recovered in the lipoprotein-free fraction. Nonreducing SDS-PAGE immunoblot
analysis provided evidence that G162C apoA-V present in the lipoprotein-free
fraction, but not that portion associated with lipoproteins, displayed altered
electrophoretic mobility consistent with disulfide-linked heterodimer formation.
Immunoprecipitation followed by liquid chromatography/mass spectrometry of human
plasma from subjects homozygous for wild-type APOA5 and c.553G>T APOA5 revealed
that G162C apoA-V forms adducts with extraneous plasma proteins including
fibronectin, kininogen-1, and others. CONCLUSIONS: Substitution of Cys for Gly at
position 162 of mature apoA-V introduces a free cysteine that forms disulfide
bonds with plasma proteins such that its lipoprotein-binding and triacylglycerol
modulation functions are compromised.
PMID- 25127533
TI - Severe bilateral ischemic retinal vasculitis following cataract surgery.
AB - This report describes two cases of severe, bilateral ischemic retinal vasculitis
following cataract surgeries at different surgical centers. In both cases, the
patient underwent bilateral cataract surgeries, performed 1 week apart for each
eye. In the perioperative period following the second of the two surgeries, both
patients developed severe, bilateral intraocular inflammation and profound vision
loss. The underlying cause of this adverse response remains unknown. The authors
suggest that the severe inflammatory reaction could be related to an
intraoperative intracameral vancomycin injection.
PMID- 25127536
TI - Immigrant and refugee health: mental health conditions.
AB - Immigrants leave their homes for unfamiliar destinations in search of better
lives for themselves and their families. Many immigrants experience profound loss
and emotional distress as they adjust to life in different societies. Despite
these challenges, the prevalence of mental health conditions among immigrants is
low, whereas children of immigrants have rates equal to those of native
populations. The prevalence of mental health conditions is high among refugees,
who comprise a specific subgroup of immigrants who have been displaced forcibly
and often have experienced severe trauma. Cultural factors, such as stigma and
somatization of emotional symptoms, make it less likely that immigrants and
refugees from certain groups will ever present to mental health subspecialists.
Strong therapeutic relationships, cultural sensitivity, involvement of family
members, judicious use of medications, and knowledge of available community
resources are important tools that can aid clinicians who treat immigrants and
refugees with mental health conditions.
PMID- 25127535
TI - Immigrant and refugee health: medical evaluation.
AB - Overseas medical screening by panel physicians for conditions that might
jeopardize US public health is required for admission to the United States by
immigrant visa or refugee status. According to protocols established by the
Centers for Disease Control and Prevention, conditions such as active
tuberculosis and substance dependence, when detected, prohibit entry to the
United States, whereas close medical follow-up after arrival is required for
individuals with other conditions. Refugees and asylees should undergo further
medical assessment by a US civil surgeon as soon as possible after arrival.
Applicants for legal permanent residence in the United States, whether by
immigrant visa or adjustment of status, must receive vaccinations comparable to
those recommended for citizens. When immigrants and refugees present to a primary
care physician, the vaccination process may not be complete, and documentation of
the extent to which it is complete might be lacking. Immigrants and refugees may
have a variety of unrecognized or untreated musculoskeletal conditions, mental
health conditions, infectious diseases, and chronic conditions.
PMID- 25127537
TI - Immigrant and refugee health: common infectious diseases.
AB - Immigrants and refugees are at risk of infectious diseases (IDs) that are rare in
the United States. Screening and treatment before entry into the United States
are required for some of these diseases, whereas quarantine is mandated for
others. The Centers for Disease Control and Prevention has published specific
recommendations for the evaluation and treatment of immigrants and refugees
before and after they arrive in the United States. In addition, immigrants and
refugees who return to their home countries are at greater risk of IDs than other
travelers. Health care professionals are required to report certain IDs to state
or local health departments.
PMID- 25127538
TI - Immigrant and refugee health: cross-cultural communication.
AB - Physicians in the United States increasingly care for culturally, linguistically,
and educationally diverse immigrants with limited English proficiency. Language
barriers contribute significantly to the health disparities experienced by
patients with limited English proficiency. Qualified professional interpreters
should be used instead of ad hoc interpreters, such as a patient's friend or
family member, an untrained bilingual staff member, or a bilingual stranger.
Children should not be used as interpreters. Physicians and other health care
professionals must be fluent to communicate with patients in another language.
Use of electronic translation systems should be avoided. Cultural competence
refers to the attitudes, knowledge, and skills needed to work well in cross
cultural situations and effectively provide care to diverse populations.
Stereotypes are perpetuated when members of a group are assumed to share cultural
values, beliefs, or attitudes. Attempting to memorize a list of what to do and
what to avoid when working with any particular group is ineffective. Every
patient's culture is multidimensional and dynamic and is not defined by race or
language group.
PMID- 25127539
TI - How do patients with severe mental diagnosis cope in everyday life - a
qualitative study comparing patients' experiences of self-referral inpatient
treatment with treatment as usual?
AB - BACKGROUND: Several hospitals in Norway provide short self-referral inpatient
treatment to patients with severe mental diagnosis. No studies have compared the
experiences of patients who have had the opportunity to self-refer to inpatient
treatment with patients who have received treatment as usual. This qualitative
study was nested within a randomised controlled trial investigating the effect of
self-referral to inpatient treatment. The aim was to explore how patients with
severe mental diagnosis coped four months after signing a contract for self
referral, as compared to patients receiving treatment as usual. METHODS: Data was
collected using qualitative individual interviews with patients with severe
mental diagnosis, conducted four months after being randomised either to a
contract for self-referral (intervention group) or to treatment as usual (control
group). RESULTS: Twenty-five patients participated in interviews - 11 from the
intervention group and 14 from the control group. Results four months after
randomisation showed that patients with a contract for self-referral appeared to
have more confidence in strategies to cope with mental illness and to apply more
active cognitive strategies. Patients with a contract also expressed less
resignation, hopelessness and powerlessness than patients without a contract. In
addition, patients with a contract seemed to be closer to the ideal of living a
"normal" life and being a "normal" person. CONCLUSION: The results indicate that
the patients who had a contract for self-referral had come further in the
recovery process and should possibly be better off during treatment.
PMID- 25127541
TI - Dominant side in single-leg stance stability during floor oscillations at various
frequencies.
AB - BACKGROUND: We investigated lateral dominance in the postural stability of single
leg stance with anteroposterior floor oscillations at various frequencies.
METHODS: Thirty adults maintained a single-leg stance on a force platform for 20
seconds per trial. Trials were performed with no oscillation (static condition)
and with anteroposterior floor oscillations (2.5-cm amplitude) at six
frequencies: 0.25, 0.5, 0.75, 1.0, 1.25 and 1.5 Hz (dynamic condition). A set of
three trials was performed on each leg in each oscillation frequency in random
order. The mean speed of the center of pressure in the anteroposterior direction
(CoPap) was calculated as an index of postural stability, and frequency analysis
of CoPap sway was performed. Footedness for carrying out mobilizing activities
was assessed with a questionnaire. RESULTS: CoPap speed exponentially increased
as oscillation frequency increased in both legs. The frequency analysis of CoPap
showed a peak <0.3 Hz at no oscillation. The frequency components at 0.25-Hz
oscillation included common components with no oscillation and those at 1.5-Hz
oscillation showed the maximum amplitude among all conditions. Postural stability
showed no significant difference between left- and right-leg stance at no
oscillation and oscillations <=1.25 Hz, but at 1.5-Hz oscillation was
significantly higher in the right-leg stance than in the left-leg stance. For the
lateral dominance of postural stability at individual levels, the lateral
difference in postural stability at no oscillation was positively correlated with
that at 0.25-Hz oscillation (r = 0.51) and negatively correlated with that at 1.5
Hz oscillation (r = -0.53). For 70% of subjects, the dominant side of postural
stability was different at no oscillation and 1.5-Hz oscillation. In the subjects
with left- or right-side dominance at no oscillation, 94% or 38% changed their
dominant side at 1.5-Hz oscillation, with a significant difference between these
percentages. In the 1.5-Hz oscillation, 73% of subjects had concordance between
the dominant side of postural stability and that of mobilizing footedness.
CONCLUSION: In static conditions, there was no lateral dominance of stability
during single-leg stance. At 1.5-Hz oscillation, the highest frequency, right
side dominance of postural stability was recognized. Functional role in
supporting leg may be divided between left and right legs according to the change
of balance condition from static to dynamic.
PMID- 25127543
TI - The laboratory diagnosis of mucopolysaccharidosis III (Sanfilippo syndrome): A
changing landscape.
AB - Mucopolysaccharidosis type III (MPS III) is characterized by progressive
neurological deterioration, behavioral abnormalities, a relatively mild somatic
phenotype, and early mortality. Because of the paucity of somatic manifestations
and the rarity of the disease, early diagnosis is often difficult. Therapy
targeting the underlying disease pathophysiology may offer the greatest clinical
benefit when started prior to the onset of significant neurologic sequelae. Here
we review current practices in the laboratory diagnosis of MPS III in order to
facilitate earlier patient identification and diagnosis. When clinical suspicion
of MPS III arises, the first step is to order a quantitative assay that screens
urine for the presence of glycosaminoglycan biomarkers using a spectrophotometric
compound (e.g., dimethylmethylene blue). We recommend testing all patients with
developmental delay and/or behavioral abnormalities as part of the diagnostic
work-up because quantitative urine screening is inexpensive and non-invasive.
Semi-quantitative urine screening assays using cationic dyes on filter paper
(e.g., spot tests) have relatively high rates of false-positives and false
negatives and are obsolete. Of note, a negative urinary glycosaminoglycan assay
does not necessarily rule out MPS because, in some patients, an overlap in
excretion levels with healthy controls may occur. All urine samples that test
positive for glycosaminoglycans with a quantitative assay should be confirmed by
electrophoresis, thin layer chromatography, or tandem mass spectrometry, which
further improves the sensitivity and specificity. The gold standard for diagnosis
remains the enzyme activity assay in cultured skin fibroblasts, leukocytes,
plasma, or serum, which can be used as a first-line diagnostic test in some
regions. Molecular genetic analysis should be offered to all families of patients
to allow genetic counseling for informed family planning. For a small number of
variants, genotype-phenotype correlations are available and can offer prognostic
value. Prenatal testing via enzyme activity assay in chorionic villi or amniotic
fluid cells is available at a limited number of centers worldwide, but whenever
possible, a molecular genetic analysis is preferred for prenatal diagnosis. To
conclude, we discuss the development of newborn screening assays in dried blood
spots and high-throughput methods for sequencing the protein-coding regions of
the genome (whole exome sequencing) and their relevance to future changes in the
MPS III diagnostic landscape.
PMID- 25127540
TI - Lung transplantation in idiopathic pulmonary fibrosis: a systematic review of the
literature.
AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a distinct form of
interstitial pneumonia with unknown origin and poor prognosis. Current
pharmacologic treatments are limited and lung transplantation is a viable option
for appropriate patients. The aim of this review was to summarize lung
transplantation survival in IPF patients overall, between single (SLT) vs.
bilateral lung transplantation (BLT), pre- and post Lung Allocation Score (LAS),
and summarize wait-list survival. METHODS: A systematic review of English
language studies published in Medline or Embase between 1990 and 2013 was
performed. Eligible studies were those of observational design reporting survival
post-lung transplantation or while on the wait list among IPF patients. RESULTS:
Median survival post-transplantation among IPF patients is estimated at 4.5
years. From ISHLT and OPTN data, one year survival ranged from 75% - 81%; 3-year:
59% - 64%; and 5-year: 47% - 53%. Post-transplant survival is lower for IPF vs.
other underlying pre-transplant diagnoses. The proportion of IPF patients
receiving BLT has steadily increased over the last decade and a half. Unadjusted
analyses suggest improved long-term survival for BLT vs. SLT; after adjustment
for patient characteristics, the differences tend to disappear. IPF patients
account for the largest proportion of patients on the wait list and while wait
list time has decreased, the number of transplants for IPF patients has increased
over time. OPTN data show that wait list mortality is higher for IPF patients vs.
other diagnoses. The proportion of IPF patients who died while awaiting
transplantation ranged from 14% to 67%. While later transplant year was
associated with increased survival, no significant differences were noted pre vs.
post LAS implementation; however a high LAS vs low LAS was associated with
decreased one-year survival. CONCLUSIONS: IPF accounts for the largest proportion
of patients awaiting lung transplants, and IPF is associated with higher wait
list and post-transplant mortality vs. other diagnoses. Improved BLT vs. SLT
survival may be the result of selection bias. Survival pre- vs. post LAS appears
to be similar except for IPF patients with high LAS, who have lower survival
compared to pre-LAS. Data on post-transplant morbidity outcomes are sparse.
PMID- 25127544
TI - The need for a research and development strategy.
PMID- 25127542
TI - Long term effects of enzyme replacement therapy in an Italian cohort of type 3
Gaucher patients.
AB - BACKGROUND: The chronic neuropathic form of Gaucher disease (GD3) is
characterised by hepatosplenomegaly, anaemia, thrombocytopenia, bone alterations
and central neurological involvement. Enzyme replacement therapy (ERT) has been
demonstrated to be effective in non neuropathic Gaucher disease, but long term
results in patients with GD3 are still limited and contrasting. A possible role
of genotype in determining the response to ERT has been hypothesised. PATIENTS
AND METHODS: All patients affected by GD3, treated with ERT, and followed-up in 4
different Italian centres (Udine, Catanzaro, Sassari and Florence) were included.
Data on clinical conditions, laboratory values, neurological and
neuropsychological examinations, radiological and electrophysiological features
were collected retrospectively from clinical records. RESULTS: Ten patients (6
females, 4 males) with four different genotypes (L444P/L444P, L444P/F231I,
P159T/unknown, C.115+1G>A/N188S) were identified. They received ERT infusions
from 3 to 21years. Haematological parameters and organomegaly improved/normalised
in all patients. Three patients showed severe progressive skeletal deformities.
6/10 patients were neurologically asymptomatic when they started ERT for systemic
symptoms. During the follow-up, 2/6 developed an important central nervous system
disease; 2/6 developed mild central symptoms; and 2/6 did not show any
neurological symptom after 5, and 20years of treatment respectively, despite the
presence of epileptiform abnormalities at the electroencephalogram. Overall,
neurological involvement worsened over time in 6/10 patients, 3 of whom developed
progressive myoclonic encephalopathy and died. CONCLUSIONS: ERT improved the
systemic manifestations in patients with GD3, but was not able to counteract the
progression of neurological symptoms in the long term.
PMID- 25127545
TI - Simplified follow-up after medical abortion using a low-sensitivity urinary
pregnancy test and a pictorial instruction sheet in Rajasthan, India--study
protocol and intervention adaptation of a randomised control trial.
AB - BACKGROUND: The World Health Organisation suggests that simplification of the
medical abortion regime will contribute to an increased acceptability of medical
abortion, among women as well as providers. It is expected that a home-based
follow-up after a medical abortion will increase the willingness to opt for
medical abortion as well as decrease the workload and service costs in the
clinic. METHODS/DESIGN: This study protocol describes a study that is a
randomised, controlled, non-superiority trial. Women screened to participate in
the study are those with unwanted pregnancies and gestational ages equal to or
less than nine weeks. The randomisation list will be generated using a
computerized random number generator and opaque sealed envelopes with group
allocation will be prepared. Randomization of the study participants will occur
after the first clinical encounter with the doctor. Eligible women randomised to
the home-based assessment group will use a low-sensitivity pregnancy test and a
pictorial instruction sheet at home, while the women in the clinic follow-up
group will return to the clinic for routine follow-up carried out by a doctor.
The primary objective of the study this study protocol describes is to evaluate
the efficacy of home-based assessment using a low-sensitivity pregnancy test and
a pictorial instruction sheet 10-14 days after an early medical abortion.
Providers or research assistants will not be blinded during outcome assessment.
To ensure feasibility of the self-assessment intervention an adaption phase took
place at the selected study sites before study initiation. This resulted in an
optimized, tailor-made intervention and in the development of the pictorial
instruction sheet with a guide on how to use the low-sensitivity pregnancy test
and the danger signs after a medical abortion. DISCUSSION: In this paper, we will
describe the study protocol for a randomised control trial investigating the
efficacy of simplified follow-up in terms of home-based assessment, 10-14 days
after a medical abortion. Moreover, a description of the adaptation phase is
included for a better understanding of the implementation of the intervention in
a setting where literacy is low and the road-connections are poor. TRIAL
REGISTRATION: Clinicaltrials.gov NCT01827995. Registered 04 May 2013.
PMID- 25127546
TI - mRNA-based vaccines synergize with radiation therapy to eradicate established
tumors.
AB - BACKGROUND: The eradication of large, established tumors by active immunotherapy
is a major challenge because of the numerous cancer evasion mechanisms that
exist. This study aimed to establish a novel combination therapy consisting of
messenger RNA (mRNA)-based cancer vaccines and radiation, which would facilitate
the effective treatment of established tumors with aggressive growth kinetics.
METHODS: The combination of a tumor-specific mRNA-based vaccination with
radiation was tested in two syngeneic tumor models, a highly immunogenic E.G7-OVA
and a low immunogenic Lewis lung cancer (LLC). The molecular mechanism induced by
the combination therapy was evaluated via gene expression arrays as well as flow
cytometry analyses of tumor infiltrating cells. RESULTS: In both tumor models we
demonstrated that a combination of mRNA-based immunotherapy with radiation
results in a strong synergistic anti-tumor effect. This was manifested as either
complete tumor eradication or delay in tumor growth. Gene expression analysis of
mouse tumors revealed a variety of substantial changes at the tumor site
following radiation. Genes associated with antigen presentation, infiltration of
immune cells, adhesion, and activation of the innate immune system were
upregulated. A combination of radiation and immunotherapy induced significant
downregulation of tumor associated factors and upregulation of tumor suppressors.
Moreover, combination therapy significantly increased CD4+, CD8+ and NKT cell
infiltration of mouse tumors. CONCLUSION: Our data provide a scientific rationale
for combining immunotherapy with radiation and provide a basis for the
development of more potent anti-cancer therapies.
PMID- 25127547
TI - Circulation of four Anaplasma phagocytophilum ecotypes in Europe.
AB - BACKGROUND: Anaplasma phagocytophilum is the etiological agent of granulocytic
anaplasmosis in humans and animals. Wild animals and ticks play key roles in the
enzootic cycles of the pathogen. Potential ecotypes of A. phagocytophilum have
been characterized genetically, but their host range, zoonotic potential and
transmission dynamics has only incompletely been resolved. METHODS: The presence
of A. phagocytophilum DNA was determined in more than 6000 ixodid ticks collected
from the vegetation and wildlife, in 289 tissue samples from wild and domestic
animals, and 69 keds collected from deer, originating from various geographic
locations in The Netherlands and Belgium. From the qPCR-positive lysates, a
fragment of the groEL-gene was amplified and sequenced. Additional groEL
sequences from ticks and animals from Europe were obtained from GenBank, and
sequences from human cases were obtained through literature searches. Statistical
analyses were performed to identify A. phagocytophilum ecotypes, to assess their
host range and their zoonotic potential. The population dynamics of A.
phagocytophilum ecotypes was investigated using population genetic analyses.
RESULTS: DNA of A. phagocytophilum was present in all stages of questing and
feeding Ixodes ricinus, feeding I. hexagonus, I. frontalis, I. trianguliceps, and
deer keds, but was absent in questing I. arboricola and Dermacentor reticulatus.
DNA of A. phagocytophilum was present in feeding ticks and tissues from many
vertebrates, including roe deer, mouflon, red foxes, wild boar, sheep and
hedgehogs but was rarely found in rodents and birds and was absent in badgers and
lizards. Four geographically dispersed A. phagocytophilum ecotypes were
identified, that had significantly different host ranges. All sequences from
human cases belonged to only one of these ecotypes. Based on population genetic
parameters, the potentially zoonotic ecotype showed significant expansion.
CONCLUSION: Four ecotypes of A. phagocytophilum with differential enzootic cycles
were identified. So far, all human cases clustered in only one of these ecotypes.
The zoonotic ecotype has the broadest range of wildlife hosts. The expansion of
the zoonotic A. phagocytophilum ecotype indicates a recent increase of the
acarological risk of exposure of humans and animals.
PMID- 25127550
TI - Association among duration of mechanical ventilation, cuff material of
endotracheal tube, and postoperative nosocomial pneumonia in cardiac surgical
patients: a prospective study.
AB - OBJECTIVES: Postoperative pulmonary complications are a burden for high-risk
surgical patients with a risk of aspiration of subglottic secretions along the
polyvinyl chloride cuff. The introduction of a polyurethane cuff diminishes
secretion leakage with a decreased rate of pneumonia. The aim of the current
analysis was to determine the time at which a polyurethane cuffed endotracheal
tube might be advantageous to prevent aspiration in a setting of high-risk
surgical patients. METHODS: The present investigation is based on published data
obtained in postoperative cardiac surgical patients undergoing operation from
2006 to 2007. Cuff pressure was kept between 20 and 26 cmH2O intraoperatively and
in the intensive care unit. The current post hoc analysis determines (1) the
discriminatory cutoff value of intubation duration for predicting postoperative
pneumonia and (2) the potential factors associated with prolonged intubation.
RESULTS: Forty-three patients (32%) were diagnosed with early postoperative
pneumonia. Receiver operating characteristics analysis revealed a cutoff value of
16.6 hours for the duration of mechanical ventilation to discriminate patients
with postoperative pneumonia. A stepwise binary logistic regression analysis
revealed that a polyvinyl chloride cuff was associated with a 10-fold increased
risk for prolonged intubation. CONCLUSIONS: The current analyses provide evidence
that among cardiac surgical patients, mechanical ventilation more than 16.6 hours
is associated with an increased likelihood of postoperative pneumonia.
PMID- 25127548
TI - Primary transcriptome map of the hyperthermophilic archaeon Thermococcus
kodakarensis.
AB - BACKGROUND: Prokaryotes have relatively small genomes, densely-packed with
protein-encoding sequences. RNA sequencing has, however, revealed surprisingly
complex transcriptomes and here we report the transcripts present in the model
hyperthermophilic Archaeon, Thermococcus kodakarensis, under different
physiological conditions. RESULTS: Sequencing cDNA libraries, generated from RNA
isolated from cells under different growth and metabolic conditions has
identified >2,700 sites of transcription initiation, established a genome-wide
map of transcripts, and consensus sequences for transcription initiation and post
transcription regulatory elements. The primary transcription start sites (TSS)
upstream of 1,254 annotated genes, plus 644 primary TSS and their promoters
within genes, are identified. Most mRNAs have a 5'-untranslated region (5'-UTR)
10 to 50 nt long (median = 16 nt), but ~20% have 5'-UTRs from 50 to 300 nt long
and ~14% are leaderless. Approximately 50% of mRNAs contain a consensus ribosome
binding sequence. The results identify TSS for 1,018 antisense transcripts, most
with sequences complementary to either the 5'- or 3'-region of a sense mRNA, and
confirm the presence of transcripts from all three CRISPR loci, the RNase P and
7S RNAs, all tRNAs and rRNAs and 69 predicted snoRNAs. Two putative riboswitch
RNAs were present in growing but not in stationary phase cells. The procedure
used is designed to identify TSS but, assuming that the number of cDNA reads
correlates with transcript abundance, the results also provide a semi
quantitative documentation of the differences in T. kodakarensis genome
expression under different growth conditions and confirm previous observations of
substrate-dependent specific gene expression. Many previously unanticipated small
RNAs have been identified, some with relative low GC contents (<= 50%) and
sequences that do not fold readily into base-paired secondary structures,
contrary to the classical expectations for non-coding RNAs in a hyperthermophile.
CONCLUSION: The results identify >2,700 TSS, including almost all of the primary
sites of transcription initiation upstream of annotated genes, plus many
secondary sites, sites within genes and sites resulting in antisense transcripts.
The T. kodakarensis genome is small (~2.1 Mbp) and tightly packed with protein
encoding genes, but the transcriptomes established also contain many non-coding
RNAs and predict extensive RNA-based regulation in this model Archaeon.
PMID- 25127549
TI - Effectiveness of screening for abdominal aortic aneurysm during echocardiography.
AB - Screening patients with abdominal aortic aneurysm (AAA) is associated with
reduced AAA-related mortality, but population screening is poorly implemented.
Opportunistic screening during imaging for other indications might be efficient.
Single-center series reported AAA rates of 0.8% to 6.5% in patients undergoing
transthoracic echocardiography (TTE), with disparities due to selection bias. In
this first multicenter study, we aimed to assess the feasibility and criteria for
screening AAA during TTE in real-life practice. During a week of May 2011, 79
centers participated in a nationwide survey. All patients aged >=65 years
requiring TTE for any indication were eligible, except for those with operated
abdominal aorta. We defined AAA by an anteroposterior diameter of the infrarenal
aorta>=30 mm. Of 1,382 consecutive patients, abdominal aorta imaging was feasible
in 96.7%, with a median delay of 1.7 minutes (>3 minutes in 3.6% of cases). We
found AAA in 50 patients (3.7%). Unknown AAA (2.7%) was more frequent in men than
women (3.7% vs 1.3%, respectively, p=0.007) and increased by age at 2.2%, 2.5%,
and 5.8% in age bands of 65 to 74, 75 to 84, and 85+ years, respectively. None of
the female participants aged <75 years had AAA. Smoking status and family history
of AAA were significantly more frequent among patients with AAA. The ascending
aorta was larger in those with AAA (36.2+/-4.7 vs 34.0+/-5.2 mm, p=0.006), and
bicuspid aortic valve and/or major aortic regurgitation were also more frequent
(8% vs 2.6%, p=0.017). In conclusion, rapid AAA screening during TTE is feasible
and should be limited to men >=65 years and women>=75 years.
PMID- 25127551
TI - Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti
cholinergic agent against skin injury induced by sulfur mustard.
AB - Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional
alkylating agent inducing edema, inflammation, and the formation of fluid-filled
blisters in the skin. Medical countermeasures against SM-induced cutaneous injury
have yet to be established. In the present studies, we tested a novel,
bifunctional anti-inflammatory prodrug (NDH 4338) designed to target
cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and
acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory
pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice
were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied
topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found
to induce skin injury characterized by edema, epidermal hyperplasia, loss of the
differentiation marker, keratin 10 (K10), upregulation of the skin wound marker
keratin 6 (K6), disruption of the basement membrane anchoring protein laminin
322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced
SM-induced dermal edema and enhanced skin re-epithelialization. This was
associated with a reduction in COX2 expression, increased K10 expression in the
suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored
basement membrane integrity, as evidenced by continuous expression of laminin 332
at the dermal-epidermal junction. Taken together, these data indicate that a
bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin
injury and may be useful as a medical countermeasure.
PMID- 25127552
TI - Australian alcohol policy 2001-2013 and implications for public health.
AB - BACKGROUND: Despite a complex and multi-faceted alcohol policy environment in
Australia, there are few comprehensive reviews of national and state alcohol
policies that assess their effectiveness and research support. In mapping the
Australian alcohol policy domain and evaluating policy interventions in each of
the core policy areas, this article provides a useful resource for researchers.
The implications for protecting public health emanating from this mapping and
evaluation of alcohol policy are also discussed. METHODS: This review considered
data from: published primary research; alcohol legislation, strategies and
alcohol-related press releases for all levels and jurisdictions of Australian
government; international publications by prominent non-governmental
organisations; and relevant grey literature. These were organised and evaluated
using the established framework offered by Thomas Babor and colleagues. RESULTS:
Findings indicated great variability in alcohol initiatives across Australia,
many of which do not reflect what is currently considered to be evidence-based
best practice. CONCLUSIONS: Research showing increasing alcohol-related harms
despite steady levels of consumption suggests a need to pursue alcohol policy
initiatives that are supported by evidence of harm-reduction. Future initiatives
should aim to increase existing alcohol controls in line with suggested best
practice in order to protect public health in Australia.
PMID- 25127553
TI - Risk factors for diarrhea hospitalization in Bangladesh, 2000-2008: a case-case
study of cholera and shigellosis.
AB - BACKGROUND: Cholera and shigellosis are endemic on the Indian subcontinent. Our
objective was to identify cholera-specific risk factors distinct from shigellosis
risk factors. METHODS: We conducted a case-case study among hospitalized
diarrheal patients, comparing those with cholera and shigellosis in International
Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) hospitals in Matlab
(rural) and Dhaka (urban) between January 1, 2000 and December 31, 2008. RESULTS:
Multivariable Poisson regression models revealed that having more than nine years
of education, compared to no education, was associated with a 39% (adjusted Risk
Ratio [aRR] = 0.61, 95% confidence interval [CI]: 0.40-0.93) decreased risk for
cholera hospitalization in Matlab and a 16% (aRR = 0.84, 95% CI: 0.75-0.94)
decreased risk in Dhaka. Having a family member with diarrhea in the past seven
days increased cholera hospitalization risk by 17% (aRR = 1.17, 95% CI: 1.09
1.26) in Matlab. CONCLUSIONS: Further studies are needed to elucidate the pathway
through which education impacts cholera risk in order to create targeted
interventions in cholera-endemic areas. Interventions seeking to reduce
transmission and facilitate hygienic practices among family members of index
cases with diarrhea should be considered, especially in rural cholera endemic
settings.
PMID- 25127555
TI - [Reply to authors].
PMID- 25127554
TI - [Self-rated health and educational level in Spain: trends by autonomous
communities and gender (2001-2012)].
AB - OBJECTIVE: To identify the trend in self-rated health in Spain by autonomous
communities (AC) in the period 2001-2012, as well as differences by gender and
age, and the influence of educational level. METHODS: A cross sectional study was
carried out using data from the National Health Surveys from 2001 to 2011-12 and
the 2009 European Survey. A descriptive analysis was conducted that included
gender, age, educational level, and the AC of residence. Logistic regression
analyses were developed to explore the temporal trend and the association between
educational level and self-rated health. The predictive capacity of the model was
calculated using the C statistic. RESULTS: The prevalence of low self-rated
health was higher in women with low educational level. Self-rated health improved
in women with high educational level (2001:18.6% vs. 2012:14.6%). The highest
prevalence of low self-rated health was observed in Andalusia, the Canary
Islands, Galicia and Murcia, with differences by gender. Low educational level
was associated with low self-rated health in most AC, with good predictive
capacity. In all AC except Asturias, low self-rated health was more frequent in
women than in men. In Spain, the prevalence of self-rated health showed no
variations in the period analyzed and improved in the Balearic Islands,
Catalonia, and Madrid. CONCLUSIONS: The prevalence of self-rated health in Spain
differed by AC. Although health was unchanged during the period considered,
inequalities were found in its temporal trend by educational level and gender,
which could lead to an increase in health inequalities in women according
educational level.
PMID- 25127556
TI - Debonding mechanisms of soft materials at short contact times.
AB - A carefully controlled, custom-built adhesion testing device was developed which
allows a precise, short dwell time on the order of milliseconds to be applied
during a contact adhesion experiment. The dwell time dependence of the adhesive
strength of crosslinked poly(dimethylsiloxane) (PDMS) in contact with glass and
uncrosslinked styrene butadiene rubber (SBR) in contact with glass and with
itself was tested with a spherical probe in a confined Johnson-Kendall-Roberts
(JKR) geometry. Analysis of the contact images revealed several unique separation
mechanisms which are dependent on dwell time and interfacial properties. PDMS
glass interfaces show essentially no dependence of adhesion on the dwell time
while the adhesive strength and separation mechanisms of SBR interfaces are shown
to vary drastically for dwell times ranging from 40 to 10,000 ms. This influence
of dwell time is particularly pronounced for polymer-polymer (SBR-SBR)
interfaces. Observations of cavitation due to trapped air pockets in the center
of the contact at very short contact times illustrate a transition between a
defect-controlled debonding and an interface-controlled debonding which has not
been previously reported.
PMID- 25127557
TI - Synthesis and characterization of a novel mesoporous silica functionalized with
[1,5 bis(di-2-pyridyl)methylene thiocarbohydrazide] and its application as
enrichment sorbent for determination of antimony by FI-HG-ETAAS.
AB - A simple, sensitive, low-cost and rapid flow injection (FI) on-line sorption
preconcentration/hydride generation system has been synchronously coupled to an
electrothermal atomic absorption spectrometer (ETAAS) for the determination of
trace amounts of Sb in aqueous environmental samples (river and sea water
samples). The system is based on retention of the analyte onto a micro-column
filled with a novel mesoporous silica functionalised with [1,5 bis(di-2-pyridyl)
methylene] thiocarbohydrazide placed in the injection valve of the FI manifold.
The adsorption capacity of the resin for Sb was found to be 160.8 umol g(-1).
Chemicals and flow variables affecting the continuous preconcentration of
antimony, the direct generation of antimony hydride and the final determination
of this element by ETAAS were evaluated. The optimized operating conditions
selected were: sample pH 5.0, sample flow rate 2.5 ml min(-1), eluent flow rate
5.4 ml min(-1), eluent 2.0% thiourea in 4.0% nitric acid. Under the optimum
conditions, the calibration graph obtained was linear over the range 0.025-2.5
MUg L(-1). At a sample frequency of 20 h(-1) and 120 s preconcentration time, the
enrichment factor was 22. The detection limit of the method (3o) was 1 ng L(-1)
for a 5.0 mL sample volume and the precision was 0.9% (RSD) for 11 replicate
determinations at 1.0 MUg L(-1) Sb. The preconcentration factor and detection
limit can be improved by increasing the preconcentration time, which can be
increased at least up to 5 min. The accuracy of the proposed method was
demonstrated by analyzing two certified reference materials and by determining
the analyte content in spiked environmental water samples. The results obtained
using this method were in good agreement with the certified values of the
standard reference materials and the recoveries for the spiked river and sea
water samples were 91.3-109.9%.
PMID- 25127558
TI - Charge-based characterisation of high-molecular-weight glutenin subunits from
common wheat by capillary isoelectric focusing.
AB - In this study, the capillary isoelectric focusing (CIEF) method for the
separation and charge characterisation of the heterogeneity of high molecular
weight-glutenin subunits (HMW-GS) in common wheat (Triticum aestivum L.) using
linear polyacrylamide (LPA) and polyvinyl alcohol (PVA) coated capillaries was
developed. Particularly good repeatability and well-resolved charge isoform
profiles were obtained by introducing a mixture of carrier ampholytes (pH 3-10
and pH 5-8), a high concentration of urea (6M) and SB3-12 as detergent in a
sample solution during separation in a PVA-coated capillary. One major and one or
two minor isoforms were observed for the individual HMW-GS. These isoforms were
satisfactorily separated using a pH gradient into two groups: y-type isoforms and
x-type isoforms encoded by the Glu-B1 locus with shorter migration times and
remaining x-type isoforms with longer times. The method produced from eight to
twelve isoforms of wheat HMW-GS with pI points in the range of 4.72-6.98.
Generally, the minor isoforms were more acidic compared with the major isoform.
The y-type subunits had an approximately neutral character (pI 6.70-6.98);
however, x-types showed a weakly acidic character (pI 4.72-5.23), with the
exception of subunits encoded by the Glu-B1 locus. The isoelectric point peak
profiles were compared with capillary zone electrophoresis (CZE)
electropherograms. Generally, the number of detected isoforms for the particular
HMW-GS detected using both methods were similar.
PMID- 25127559
TI - Evaluation of immunoglobulins in bovine colostrum using laser induced
fluorescence.
AB - The objective of the present study was to exploit laser induced fluorescence
(LIF) as a spectrochemical analytical technique for evaluation of immunoglobulin
(IgG) in bovine colostrum. Colostrum samples were collected from different
American Holstein cows at different times after calving. Four samples were
gathered from each cow; the first three samples were obtained from the first
three milkings (colostrum) and the fourth sample (milk) was obtained a week after
calving. It has been demonstrated that LIF can be used as a simple, fast,
sensitive and less costly spectrochemical analytical technique for qualitative
estimation of IgG in colostrum. LIF results have been confirmed via the
quantitative evaluation of IgG in the same samples adopting the single radial
immunodiffusion conventional technique and a very good agreement has been
obtained. Through LIF it was possible to evaluate bovine colostrum after
different milking times and to differentiate qualitatively between colostrum from
different animals which may reflect their general health status. A fluorescence
linear calibration curve for IgG concentrations from 0 up to 120 g L(-1) has been
obtained. In addition, it is feasible to adopt this technique for in situ
measurements, i.e. in dairy cattle farms as a simple and fast method for
evaluation of IgG in bovine colostrum instead of using lengthy and complicated
conventional techniques in laboratories.
PMID- 25127560
TI - Quantum dots and p-phenylenediamine based method for the sensitive determination
of glucose.
AB - By introducing p-phenylenediamine (PPD) to the hybrid system of Mn-doped CdS/ZnS
quantum dots (QDs) and glucose oxidase (GOD), a sensitive label-free method was
proposed for direct detection of glucose. With glucose and PPD as substrates, 2,5
diamino-N,N'-di-(4-aminophenyl)-2,5-cyclohexadiene-1,4-diimine (DDACD) that
intensively quenches the fluorescence of QDs can be produced by the catalysis of
GOD. A detection limit as low as 3.2 MUM was obtained with the high-efficient
fluorescence quencher. Two linear ranges, from 5.0 MUM to 1000 MUM and from 1.0
mM to 10.0 mM, were identified between time-gated fluorescence intensity and the
concentration of glucose. It is shown that the newly proposed methods have high
selectivity for glucose over other saccharides and coexisting biological species
in serum. The method can be used directly to determine glucose in normal adult
human serum without any complicated sample pretreatments. The recovery rate and
repeatability of the method were also shown to be satisfactory.
PMID- 25127561
TI - A novel electrochemiluminescence tetracyclines sensor based on a Ru(bpy)32+-doped
silica nanoparticles/Nafion film modified electrode.
AB - A novel method for the determination of tetracyclines (TCs) using
electrochemiluminescence (ECL) based on a Ru(bpy)3(2+)-doped silica nanoparticles
(RuSiNPs)/Nafion film modified electrode is presented in this paper. The RuSiNPs
were prepared by a water-in-oil microemulsion method. The characterization
results indicated that the thus-prepared RuSiNPs presented a uniform size of 45
nm and retained the original electrochemical properties of Ru(bpy)3(2+).
Importantly, the ECL response on RuSiNPs/Nafion film modified electrode was
greatly enhanced by TCs. Under the optimum conditions, the ECL intensity versus
the concentration of TCs was found to be linear over the range of 1-100 MUmol L(
1) for tetracycline (TC), 0.1-100 MUmol L(-1) for oxytetracycline (OTC) and 1-100
MUmol L(-1) for chlortetracycline (CTC). The detection limits (S/N=3) were 0.23
MUmol L(-1) for TC, 0.10 MUmol L(-1) for OTC and 0.16 MUmol L(-1) for CTC.
Moreover, due to the electrostatic interaction between Ru(bpy)3(2+) and silica
matrix, the leaching of Ru(bpy)3(2+) was greatly reduced, therefore, the ECL
sensor exhibited excellent repeatability and stability in the detection of TCs.
Based on these investigations, the proposed ECL approach was successfully used to
analyze the TCs content in drugs.
PMID- 25127562
TI - Electronic nose and chiral-capillary electrophoresis in evaluation of the quality
changes in commercial green tea leaves during a long-term storage.
AB - Electronic nose and capillary electrophoresis were applied in quality control of
green tea samples subjected to long-term storage. Twelve representative green
teas were considered, available as an "aged" (tea leaves stored during a long
term period of two years) and/or "not aged" (fresh products) samples. Their
infusions were analyzed by an electronic nose, equipped with an array of six
metal oxide semiconductor (MOS) sensors to obtain olfactive fingerprints of the
volatile compounds in the infusions headspace. Upon training and chemometric
analysis of acquired data (linear discriminant analysis), the electronic nose was
found to be able in correctly classifying unknown samples as "aged" or "not
aged". Concomitantly, the infusion samples were analyzed by Cyclodextrin-modified
Micellar Electrokinetic Chromatography (CD-MEKC) for determination of catechins.
The analysis of seven most represented catechins and the methylxanthines
theobromine and caffeine revealed a general loss of the polyphenols in each of
the considered aged samples (up to 45%, w/w). In addition, the applied
enantioselective method based on (2-hydroxypropyl)-beta-cyclodextrin (HP-betaCD)
as chiral selector, was exploited for the estimation of (+)-Gallocatechin in the
presence of (-)-Gallocatechin; the latter, as the non-native enantiomer, can be
associated to the epimerisation of (-)-Epigallocatechin and was assumed as a
marker occurring in case of uncorrected storage conditions of tea leaves.
Interestingly, it was observed that epimerization did not significantly occur
during aging. The application of CD-MEKC and electronic nose allowed for a fast
characterization of green teas taking into account that the aroma is a decisive
parameter for the acceptance of the product, whereas the catechins content is
associated to the biological value.
PMID- 25127563
TI - Analytical methods for the determination of DEHP plasticizer alternatives present
in medical devices: a review.
AB - Until 2010, diethylhexylphthalate (DEHP) was the plasticizer most commonly used
to soften PVC medical devices (MDs), because of a good efficiency/cost ratio. In
flexible plasticized PVC, phthalates are not chemically bound to PVC and they are
released into the environment and thus may come into contact with patients. The
European Directive 2007/47/CE, classified DEHP as a product with a toxicity risk
and restricted its use in MDs. MD manufacturers were therefore forced to quickly
find alternatives to DEHP to maintain the elasticity of PVC nutrition tubings,
infusion sets and hemodialysis lines. Several replacement plasticizers, so-called
"alternative to DEHP plasticizers" were incorporated into the MDs. Nowadays, the
risk of exposure to these compounds for hospitalized patients, particularly in
situations classified "at risk", has not yet been evaluated, because migrations
studies, providing sufficient exposure and human toxicity data have not been
performed. To assess the risk to patients of DEHP plasticizer alternatives,
reliable analytical methods must be first developed in order to generate data
that supports clinical studies being conducted in this area. After a brief
introduction of the characteristics and toxicity of the selected plasticizers
used currently in MDs, this review outlines recently analytical methods available
to determine and quantify these plasticizers in several matrices, allowing the
evaluation of potential risk and so risk management.
PMID- 25127564
TI - Metal organic frameworks/macroporous carbon composites with enhanced stability
properties and good electrocatalytic ability for ascorbic acid and hemoglobin.
AB - The thermal, water and electrochemical stability of Cu-based metal organic
frameworks (Cu-MOFs) confined in macroporous carbon (MPC) hybrids has been
investigated. Thermogravimetric analyses, X-Ray diffraction, scanning electron
microscopy, and cyclic voltammetry were employed to confirm the stability of pure
Cu-MOFs, MPC, and Cu-MOFs-MPC. As compared to pure Cu-MOFs, the porous composite
materials of MPC and Cu-MOFs interact and seem to form new materials having
homogenous structure and chemistry, which show structural stability in aqueous
media and electrochemical stability in phosphate buffer solution (PBS pH 7.4).
The detection of ascorbic acid and hemoglobin is performed as an electrochemical
probe, indicating Cu-MOFs-MPC holds great promise for the design of
electrochemical sensors.
PMID- 25127565
TI - Detection of copper, lead, cadmium and iron in wine using electronic tongue
sensor system.
AB - An array of 10 potentiometric chemical sensors has been applied to the detection
of total Fe, Cu, Pb and Cd content in digested wine. As digestion of organic
matter of wine is necessary prior to the trace metal detection using
potentiometric sensors, sample preparation procedures have been optimized.
Different variants of wet and microwave digestion and dry ashing, 14 conditions
in total, have been tested. Decomposition of organic matter was assessed using
Fourier transform mid-infrared spectroscopy and total phenolic content. Dry
ashing was found to be the most effective method of wine digestion. Measurements
with sensors in individual solutions of Fe(III), Cu(II), Pb(II) and Cd(II)
prepared on different backgrounds have shown that their detection limits were
below typical concentration levels of these metals in wines and, in the case of
Cu, Pb and Cd below maximum allowed concentrations. Detection of Fe in digested
wine samples was possible using discrete iron-sensitive sensors with chalcogenide
glass membranes with RMSEP of 0.05 mmol L(-1) in the concentration range from
0.0786 to 0.472 mmol L(-1). Low concentration levels of Cu, Pb and Cd in wine and
cross-sensitivity of respective sensors resulted in the non-linearity of their
responses, requiring back-propagation neural network for the calibration.
Calibration models have been calculated using measurements in the model mixed
solutions containing all three metals and a set of digested wine sample. RMSEP
values for Cu, Pb and Cd were 3.9, 39 and 1.2 MUmol L(-1) in model solutions and
2, 150 and 1 MUmol L(-1) in digested wine samples.
PMID- 25127566
TI - A miniaturized capacitively coupled plasma microtorch optical emission
spectrometer and a Rh coiled-filament as small-sized electrothermal vaporization
device for simultaneous determination of volatile elements from liquid
microsamples: spectral and analytical characterization.
AB - A low power and low argon consumption (13.56 MHz, 15 W, 150 ml min(-1))
capacitively coupled plasma microtorch interfaced with a low-resolution
microspectrometer and a small-sized electrothermal vaporization Rh coiled
filament as liquid microsample introduction device into the plasma was
investigated for the simultaneous determination of several volatile elements of
interest for environment. Constructive details, spectral and analytical
characteristics, and optimum operating conditions of the laboratory equipment for
the simultaneous determination of Ag, Cd, Cu, Pb and Zn requiring low
vaporization power are provided. The method involves drying of 10 MUl sample at
100 degrees C, vaporization at 1500 degrees C and emission measurement by capture
of 20 successive spectral episodes each at an integration time of 500 ms.
Experiments showed that emission of elements and plasma background were disturbed
by the presence of complex matrix and hot Ar flow transporting the microsample
into plasma. The emission spectrum of elements is simple, dominated by the
resonance lines. The analytical system provided detection limits in the ng ml(-1)
range: 0.5(Ag); 1.5(Cd); 5.6(Cu); 20(Pb) and 3(Zn) and absolute detection limits
of the order of pg: 5(Ag); 15(Cd); 56(Cu); 200(Pb) and 30(Zn). It was
demonstrated the utility and capability of the miniaturized analytical system in
the simultaneous determination of elements in soil and water sediment using the
standard addition method to compensate for the non-spectral effects of alkali and
earth alkaline elements. The analysis of eight certified reference materials
exhibited reliable results with recovery in the range of 95-108% and precision of
0.5-9.0% for the five examined elements. The proposed miniaturized analytical
system is attractive due to the simple construction of the electrothermal
vaporization device and microtorch, low costs associated to plasma generation,
high analytical sensitivity and easy-to-run for simultaneous multielemental
analysis of liquid microsamples.
PMID- 25127567
TI - Evaluation of surface-enhanced Raman scattering detection using a handheld and a
bench-top Raman spectrometer: a comparative study.
AB - Surface enhanced Raman scattering (SERS) detection using a handheld Raman
spectrometer and a bench-top Raman spectrometer was systemically evaluated and
compared in this study. Silver dendrites were used as the SERS substrate, and two
pesticides, maneb and pyrrolidine dithiocarbamate-ammonium salt (PDCA) were used
as the analytes. Capacity and performance were evaluated based on spectral
resolution, signal variation, quantitative capacity, sensitivity, flexibility and
intelligence for SERS detection. The results showed that the handheld Raman
spectrometer had better data consistency, more accurate quantification capacity,
as well as the capacity of on-site and intelligence for qualitative and semi
quantitative analysis. On the other hand, the bench-top Raman spectrometer showed
about 10 times higher sensitivity, as well as flexibility for optimization of the
SERS measurements under different parameters such as laser power output,
collective time, and objective magnification. The study on the optimization of
SERS measurements on a bench-top spectrometer provides a useful guide for
designing a handheld Raman spectrometer, specifically for SERS detection. This
evaluation can advance the application of a handheld Raman spectrometer for the
on-site measurement of trace amounts of pesticides or other chemicals.
PMID- 25127568
TI - Non-covalent conjugation of CdTe QDs with lysozyme binding DNA for fluorescent
sensing of lysozyme in complex biological sample.
AB - Water-soluble cysteamine (CA) capped CdTe quantum dots (QDs) conjugated with
lysozyme binding DNA (LBD) was constructed for luminescent sensing of lysozyme by
forming a ternary self-assembly complex. Addition of negatively charged lysozyme
binding DNA to the positively charged CA capped CdTe QDs buffer solution (Tris
HCl pH 7.4) could lead to the formation of QDs-LBD complex through electrostatic
interactions. Once lysozyme was introduced into the CdTe QDs-LBD system, it could
bind specifically with the QDs-LBD complex, resulting in fluorescence emission
enhancement of the QDs due to the surface inert of QDs. At a given amount of LBD
and CdTe QDs (LBD: QDs=2: 1), the fluorescence intensity enhancement of QDs was
linear with lysozyme concentration over the range of 8.9-71.2 nM, with a
detection limit of 4.3 nM. Due to the specific binding of LBD with lysozyme, this
approach displayed high selectivity for lysozyme recognition. The sensing
mechanism was confirmed by DLS and zeta potential measurement, and agarose gel
electrophoresis experiment. Furthermore, the proposed CA-capped CdTe QDs-LBD
sensor was applied to lysozyme detection in mouse serum and human morning urine
samples, which showed high sensitivity and selectivity in the complex biological
sample.
PMID- 25127569
TI - A sensitive flow-based procedure for spectrophotometric speciation analysis of
inorganic bromine in waters.
AB - A flow-based system with solenoid micro-pumps and long path-length
spectrophotometry for bromate and bromide determination in drinking water is
proposed. The method is based on the formation of an unstable dye from the
reaction between bromate, 2-(5-dibromo-2-pyridylazo)-5-(diethylamino)phenol (5-Br
PADAP) and thiocyanate ions. A multivariate optimization was carried out. A
linear response was observed between 5.0 and 100 ug L(-1) BrO3(-) and the
detection limit was estimated as 2.0 ug L(-1) (99.7% confidence level). The
coefficient of variation (n=20) and sampling rate were estimated as 1.0% and 40
determinations per hour, respectively. Reagent consumption was estimated as 0.17
ug of 5-Br-PADAP and 230 MUg of NaSCN per measurement, generating 6.0 mL of
waste. Bromide determination was carried out after UV-assisted conversion with
K2S2O8 using 300 uL of sample within the range 20-400 ug L(-1) Br(-). The
generated bromate was then determined by the proposed flow system. The results
for tap and commercial mineral water samples agreed with those obtained with the
reference procedure at the 95% confidence level. The proposed procedure is
therefore a sensitive, environmentally friendly and reliable alternative for
inorganic bromine speciation.
PMID- 25127570
TI - Construction of an electrochemical sensor based on amino-functionalized metal
organic frameworks for differential pulse anodic stripping voltammetric
determination of lead.
AB - Metal-organic frameworks composite materials have received tremendous attention
because of their versatile structures and tunable porosity for various
applications. Herein, amino-functionalized metal-organic frameworks (NH2
Cu3(BTC)2; BTC=benzene-1,3,5-tricarboxylate) was prepared and used as a novel
electrode modifier for the determination of trace levels of lead. NH2-Cu3(BTC)2
shows quite a good capability for the efficient adsorption of lead from aqueous
solutions. The parameters affecting the electrochemical process, such as
electrolyte solution pH, the amount of NH2-Cu3(BTC)2 suspension, accumulation
potential and accumulation time, were investigated in detail. Under the optimal
conditions, the electrochemical sensor exhibited a linear response to the
concentration of lead in the range of 1.0*10(-8)-5.0*10(-7) mol L(-1)
(R(2)=0.9951) with a detection limit of 5.0*10(-9) mol L(-1). The relative
standard deviation of 11 successive scans was 3.10% for 1.0*10(-8) mol L(-1)
lead. The method was validated with certified reference material (stream sediment
and milk powder) and the analytical results coincided well with the certified
values. Furthermore, the method was successfully applied to the determination of
target analytes in tap and lake water samples and good recoveries were obtained
from different spiked values.
PMID- 25127571
TI - Rapid chemiluminescent sandwich enzyme immunoassay capable of consecutively
quantifying multiple tumor markers in a sample.
AB - Using the role of p-iodophenol in enzyme assay, enhanced 1,1'-oxalyldiimidazole
chemiluminescent enzyme immunoassays (ODI-CLEIAs) were developed to consecutively
quantify trace levels of triple tumor markers, such as alpha fetoprotein (AFP),
carcinoembryonic antigen (CEA), and prostate specific antigen (PSA) in a sample.
Due to the high sensitivity of enhanced ODI-CLEIAs, it was possible to fix the
incubation times (1) to capture a tumor marker with two antibodies, which are
primary antibody immobilized on the surface of polystyrene strip-well and
detection antibody-conjugated horseradish peroxidase (HRP), and (2) to form
resorufin with the addition of substrates (e.g., Amplex Red, H2O2) in order to
quantify triple markers in human serum. Enhanced ODI-CLEIAs capable of
consecutively and rapidly quantifying triple markers with the same incubation
time were more sensitive than conventional enzyme-linked immunosorbent assay
(ELISA) capable of separately and slowly quantifying them with different
incubation times. In addition, accuracy, precision, and recovery of enhanced ODI
CLEIAs in the presence of p-iodophenol were acceptable within statistical error
range.
PMID- 25127572
TI - Coumarins as turn on/off fluorescent probes for detection of residual acetone in
cosmetics following headspace single-drop microextraction.
AB - In this work, a new method based on headspace-single drop microextraction for the
determination of residual acetone in cosmetics by microfluorospectrometry is
proposed. Acetone causes fluorescence changes in a 2.5 uL-ethanolic drop (40%
v/v) containing 3.10(-4) mol L(-1) 7-hydroxy-4-methylcoumarin ('turn off') or
6.10(-6) mol L(-1) 7-diethylamino-4-methylcoumarin ('turn on'). Polarity and
ability to form hydrogen bonds of short chain alcohols (polar protic solvents)
were crucial in order to observe these changes in the presence of acetone (polar
aprotic solvent). Parameters related with the HS-SDME procedure were studied,
namely headspace volume, composition, volume and temperature of drop,
microextraction time, stirring rate, mass and temperature of sample, as well as
the effect of potential interferents (alcohols and fragrances). The high
volatility of acetone allows its extraction from an untreated cosmetic sample
within 3 min. A detection limit of 0.26 ug g(-1) and repeatability, expressed as
relative standard deviation, around 5% were reached. Accuracy of the proposed
methodology was evaluated by means of recovery studies. The method was
successfully used to analyze different cosmetics. Simplicity and high sample
throughput can be highlighted.
PMID- 25127573
TI - Enzymatic tumour tissue digestion coupled to SPE-UPLC-Tandem Mass Spectrometry as
a tool to explore paclitaxel tumour penetration.
AB - Paclitaxel is a good compound for regional (intraperitoneal) chemotherapy of
peritoneal carcinomatosis. During IPEC, a cytotoxic solution is circulated in the
peritoneal cavity, thereby promoting close contact between the cytotoxic agent
and the exposed (residual) tumour tissue. To further explore the role of PTX in
this type of treatment and study the impact of treatment modalities on tumour
tissue penetration, in-vivo animal experiments were set-up. In literature, PTX
tumour uptake is frequently studied using autoradiography and/or fluorescence
microscopy techniques. Owing to their semi-quantitative nature on one hand and
the difficulty of incorporating imaging data within a pharmacokinetic
pharmacodynamic modelling framework on the other hand, we set out to develop a
validated assay for the quantification of PTX in tumour tissue samples.
Furthermore, in order to maximise spatial resolution, care was taken to minimise
the sample weight necessary for the analysis. Based on an enzymatic tumour tissue
digestion protocol, an easy, less labour-intensive, when compared to mechanical
tissue disruption techniques, method was developed. Through validation
experiments we showed that our method reliably quantifies PTX in a working range
of 30-8000 ng/g tumour tissue. Finally, using samples from the in-vivo
experiments we demonstrated the suitability of the developed method.
PMID- 25127574
TI - Organo-modified layered double hydroxide-catalyzed Fenton-like ultra-weak
chemiluminescence for specific sensing of vitamin B12 in egg yolks.
AB - In general, the chemiluminescence (CL) sensing of vitamin B12 is achieved by
determining Co(II) liberated from acidified vitamin B12 by a luminol system.
However, the luminol system for sensing vitamin B12 has poor selectivity due to
serious interference from other metal ions. In this study, as a novel CL
amplifier of the Co(II)+H2O2+OH(-) ultra-weak CL reaction (Fenton-like system),
dodecylbenzene sulfonate (DBS)-layered double hydroxides (LDHs) have been applied
to the specific determination of vitamin B12 by liberating Co(II). The CL
intensity increased with increasing the concentration of vitamin B12 in a wide
range from 1.0 ng mL(-1) to 5 MUg mL(-1) with a detection limit of 0.57 ng mL(-1)
(S/N=3). The proposed method has been successfully applied to determine vitamin
B12 in egg yolk with simple procedures, shorter time and higher selectivity.
Recoveries from spiked real samples were 96-103%. The results of the proposed
method for sensing vitamin B12 in real samples were agreed with those obtained by
the standard inductively coupled plasma mass spectrometry (ICP-MS) method. To the
best of our knowledge, this is the first report on the CL sensing of vitamin B12
with high selectivity in the absence of luminol.
PMID- 25127575
TI - Selective mixed-bed solid phase extraction of atrazine herbicide from
environmental water samples using molecularly imprinted polymer.
AB - A novel approach for the selective extraction of organic target compounds from
water samples has been developed using a mixed-bed solid phase extraction (mixed
bed SPE) technique. The molecularly imprinted polymer (MIP) particles are
embedded in a network of silica gel to form a stable uniform porous bed. The
capabilities of this method are demonstrated using atrazine as a model compound.
In comparison to conventional molecularly imprinted-solid phase extraction
(MISPE), the proposed mixed-bed MISPE method in combination with gas
chromatography-mass spectrometry (GC-MS) analysis enables more reproducible and
efficient extraction performance. After optimization of operational parameters
(polymerization conditions, bed matrix ingredients, polymer to silica gel ratio,
pH of the sample solution, breakthrough volume plus washing and elution
conditions), improved LODs (1.34 ug L(-1) in comparison to 2.25 ug L(-1) obtained
using MISPE) and limits of quantification (4.5 ug L(-1) for mixed-bed MISPE and
7.5 ug L(-1) for MISPE) were observed for the analysis of atrazine. Furthermore,
the relative standard deviations (RSDs) for atrazine at concentrations between 5
and 200 ug L(-1) ranged between 1.8% and 6.3% compared to MISPE (3.5-12.1%).
Additionally, the column-to-column reproducibility for the mixed-bed MISPE was
significantly improved to 16.1%, compared with 53% that was observed for MISPE.
Due to the reduced bed-mass sorbent and at optimized conditions, the total amount
of organic solvents required for conditioning, washing and elution steps reduced
from more than 25 mL for conventional MISPE to less than 2 mL for mixed-bed
MISPE. Besides reduced organic solvent consumption, total sample preparation time
of the mixed-bed MISPE method relative to the conventional MISPE was reduced from
more than 20 min to less than 10 min. The amount of organic solvent required for
complete elution diminished from 3 mL (conventional MISPE) to less than 0.4 mL
with the mixed-bed technique shows its inherent potential for online operation
with an analytical instrument. In order to evaluate the selectivity and matrix
effects of the developed mixed-bed MISPE method, it was applied as an extraction
technique for atrazine from environmental wastewater and river water samples.
PMID- 25127576
TI - Reversible modulation of gold nanoclusters photoluminescence based on
electrochromic poly(methylene blue).
AB - Reversible photoluminescence (PL) switches based on a complex of gold
nanoclusters and electrochromic poly(methylene blue) (PMB) were realized. The
gold nanoclusters PL of hybrid device can be modulated reversibly under
electrochemical stimulation. Such an electrochromic device presents several
advantages, such as large fluorescence contrast under reduction and oxidation
potentials, good reversibility and excellent long-time stability. This simple
protocol is anticipated to offer important hints for other nanoclusters and
electrochromic materials in the field of photoelectric devices.
PMID- 25127577
TI - Evaluation of transformer insulating oil quality using NIR, fluorescence, and NMR
spectroscopic data fusion.
AB - Power transformers are essential components in electrical energy distribution.
One of their most important parts is the insulation system, consisting of Kraft
paper immersed in insulating oil. Interfacial tension and color are major
parameters used for assessing oil quality and the system's degradation. This work
proposes the use of near infrared (NIR), molecular fluorescence, and (1)H nuclear
magnetic resonance (NMR) spectroscopy methods combined with chemometric
multivariate calibration methods (Partial Least Squares - PLS) to predict
interfacial tension and color in insulating mineral oil samples. Interfacial
tension and color were also determined using tensiometry and colorimetry as
standard reference methods, respectively. The best PLS model was obtained when
NIR, fluorescence, and NMR data were combined (data fusion), demonstrating
synergy among them. An optimal PLS model was calculated using the selected group
of variables according to their importance on PLS projections (VIP). The root
mean square errors of prediction (RMSEP) values of 2.9 mN m(-1) and 0.3 were
estimated for interfacial tension and color, respectively. Mean relative standard
deviations of 1.5% for interfacial tension and 6% for color were registered,
meeting quality control requirements set by electrical energy companies. The
methods proposed in this work are rapid and simple, showing great advantages over
traditional approaches, which are slow and environmentally unfriendly due to
chemical waste generation.
PMID- 25127578
TI - Electrochemiluminescence on-a-chip: towards a hand-held electrically powered
optofluidic source.
AB - We report a microfluidic platform that integrates several parallel optical
sources based on electrochemiluminescence (ECL) of 9,10-diphenylanthracene (DPA)
as luminophore agent. The annihilation of DPA radicals provides a low wavelength
emission at lambda=430 nm in the blue-visible range. By varying the distance
between electrodes for each ECL integrated source, this glass/PDMS/glass platform
enabled a systematic investigation of the main electrochemical parameters
involved in ECL. These parameters have been studied either in a static mode or in
a dynamic one. Even at slow flow rate (~2 ul s(-1)), the renewal of electroactive
species could be easily promoted inside the microfluidic channel which gives rise
to a stable optical intensity for several minutes. Compared with traditional
optically pumped dye sources, this microfluidic system demonstrates that ECL can
be easily implemented on chip for producing much compact optofluidic sources.
Such simply electrically powered system-on-chip would surely encourage the future
of hand-held uTAS devices with integrated fast detection and embedded
electronics.
PMID- 25127579
TI - A separation of tyramine on a 2-(4-methoxyphenyl)ethylamine imprinted polymer: an
answer from theoretical and experimental studies.
AB - A 2-(4-methoxyphenyl)ethylamine imprinted polymer (MIP) was successfully applied
for the selective separation of tyramine. A computational analysis was used to
predict the affinity of the polymer matrix towards tyramine and a preliminary
experimental evaluation was made for the target analyte. Then the experimental
analysis of polymer towards tyramine was continued. The binding sites were
characterized with employment of the Langmuir and Freudlich models. After the
optimization of solid phase extraction towards tyramine, the most appropriate
systems for the extraction steps were chosen: methanol-water 85:15 v/v for the
loading and the washing as well as 0.04 M aq. ammonium acetate-methanol 30:70 v/v
for the elution steps. The biogenic compounds as tryptamine, serotonin,
octopamine, synephrine, and l-tyrosine were used for the selectivity study on the
basis of binding capacities of the analytes on the imprinted and the non
imprinted polymers. The theoretical approach to obtained results allowed to
explain the adsorption selectivity of the tested polymer. Finally, the complex
matrix of bovine serum albumin was used to show the usefulness of imprinted
material for bioanalysis. The obtained recoveries showed the superiority of MIP
over the commercial sorbent C18. Total recoveries of tyramine from spiked bovine
serum albumin sample were determined as: 95+/-2%, 14+/-3%, and 1.9+/-0.4% for the
imprinted, non-imprinted, and commercial C18 sorbents, respectively.
PMID- 25127580
TI - Evaluation of internal standardization for the determination of semivolatile
analytes in difficult matrices by simultaneous multielement atomic absorption
spectrometry.
AB - The aim of the present work is to investigate the use of the internal
standardization technique combined with permanent chemical modification for the
determination of two semivolatile analytes, such as As and Se, in difficult
matrices by electrothermal atomic absorption spectrometry. Bismuth and tellurium
have been evaluated as internal standards to minimize matrix effects on the
direct determination of selenium and arsenic in sediments, by simultaneous
electrothermal atomic absorption spectrometry using graphite tubes with
integrated platform, pre-treated with different masses of Zr and Ir as permanent
modifier. A Perkin-Elmer SIMAA 6000 simultaneous multielement spectrometer was
used to study the correlation between two integrated absorbance signals. Matrix
effects were evaluated by calculating the slope ratio between the analytical
curve obtained from reference solutions prepared in 1.0% (v/v) HNO3 and
analytical curve obtained from IS additions in matrix solutions. The results
showed that Te was the optimal internal standard and 200 MUg Zr and 20 MUg Ir was
the optimal permanent chemical modifier for both analytes. The instrumental
limits of detection for As and Se were 1.48 and 1.96 MUg L(-1) without the use of
an internal standard and 0.59 and 0.35 MUg L(-1) when Te was used as an internal
standard, respectively. Relative standard deviations for a sample with matrix
effect containing 100 MUg L(-1) As and 200 MUg L(-1) Se were 1.3% and 2.3% (n=20)
using 100 MUg L(-1) Te, respectively, and for a standard solution sample
containing 100 MUg L(-1) As and 200 MUg L(-1) Se were 3.0% and 1.2% (n=20) using
100MUgL(-1) Te, respectively. The accuracy of the proposed method was evaluated
by an addition-recovery experiment and by the analysis of different certified
reference materials. The recovered values were in the 95-100% range for both
analytes.
PMID- 25127581
TI - GC-MS and FTIR evaluation of the six benzoyl-substituted-1-pentylindoles:
isomeric synthetic cannabinoids.
AB - This report compares the GC-MS and FTIR properties of all 6 regioisomeric benzoyl
substituted-1-n-pentylindoles. These compounds have the benzoyl-group attached at
each of the possible ring substituent positions of the indole ring. The six
compounds have the same elemental composition C20H21NO yielding identical nominal
and exact masses. Additionally, the substituents attached to the indole ring,
benzoyl- and 1-n-pentyl-groups, are identical for all six isomers. The electron
ionization mass spectra show equivalent regioisomeric major fragments resulting
from cleavage of the groups attached to the central indole nucleus. Fragment ions
occur at m/z 77 and 105 for the phenyl and benzoyl cations common to all six
regioisomeric substances. Fragmentation of the benzoyl and/or pentyl groups
yields the cations at m/z 234, 220, 214, 186 and 144. While the relative
abundance of the ions varies among the six regioisomeric substances the 1-n
pentyl-3-benzoylindole and 1-n-pentyl-5-benzoylindole share very similar relative
abundances for the major fragment ions. Chromatographic separations on a
capillary column containing a 0.5MUm film of 100% trifluoropropyl methyl
polysiloxane (Rtx-200) provided excellent resolution of these six compounds. The
elution order appears related to the relative distance between the two indole
substituted groups. The latest eluting compounds (highest retention time) have
the two substituents on opposite sides of the indole nucleus. Infrared absorption
spectral data show the carbonyl absorption band for each of the benzoylindoles
and provide distinguishing and characteristic information to individualize each
of the regioisomers in this set of compounds.
PMID- 25127582
TI - Multiple headspace solid-phase microextraction for quantifying volatile free
fatty acids in cheeses.
AB - Multiple headspace solid-phase microextraction (MHS-SPME) has been utilized for
the quantitative determination of 9 volatile free fatty acids (FFAs) in cheeses,
in combination with gas-chromatography and flame-ionization detection (GC-FID).
Variables affecting HS-SPME and MHS-SPME were optimized to attain adequate
sensitivity while allowing correct application of the MHS method. Thus, the MHS
SPME method was successfully performed when using 0.3g of cheese and 1 mL of NaCl
(sat. solution), which is subjected to four consecutive extractions using the
carboxen-polydimethylsyloxane (CAR-PDMS) as the commercial SPME coating, 40 min
of HS extraction time at 45 degrees C, and 6 min of desorption time in the GC
injector at 290 degrees C. The MHS-SPME permitted the calculation of beta values,
which range from 0.72+/-0.01-0.95+/-0.02, depending on the cheese studied. Later,
this beta parameter is used to perform quantitation for the 9 volatile FFAs after
just a single HS-SPME extraction, using an external solvent calibration curve.
The validity of the utilization of an external solvent calibration was tested
with aqueous standards of volatile FFAs, getting average recoveries higher than
81.2%. Quantitation by MHS-SPME was free of matrix interferences despite
measuring a complex cheese sample. The optimized method was validated, presenting
inter-day reproducibility values (as RSD in %) lower than 13%, and limits of
detection down to 7 ug kg(-1). The method was also compared with a conventional
extraction method such as solid-phase extraction for the studied cheeses
elaborated with goat milk, generating comparable results. To our knowledge, this
is the first time that MHS-SPME has been applied to volatiles in cheeses.
PMID- 25127583
TI - Novel miniaturized sensors for potentiometric batch and flow-injection analysis
(FIA) of perchlorate in fireworks and propellants.
AB - Three planar miniaturized perchlorate membrane sensors (3*5 mm(2)) are prepared
using a flexible Kaptan substrate coated with nitron-perchlorate (NT-ClO4)
[sensor 1], methylene blue-perchlorate (MB-ClO4) [sensor II] and indium-porphyrin
(In-Por) [sensor III] as electroactive materials in PVC membranes plasticized
with 2-NPPE. Sensors I, II and III display near-Nernstian response for 1.0*10(-5)
1.0*10(-2), 3.1*10(-5)-1.0*10(-2) and 3.1*10(-6)-1.0*10(-2) mol L(-1) ClO4(-)
with lower detection limits of 6.1*10(-6), 6.9*10(-6) and 1.2*10(-6) mol L(-1),
and anionic calibration slopes of 50.9+/-0.4, 48.4+/-0.4 and 57.7+/-0.3 mV
decade(-1), respectively. Methods for determining perchlorate using these sensors
offer many attractive advantages including simplicity, flexibility, cost
effectiveness, wide linear dynamic response range (0.1-1000 ppm), low detection
limit (<1.2*10(-6) mol L(-1)=0.1 ppm), small sample test volume (100 MUL),
safety, short response time (<20 s), long life span (~8 weeks), and extended wide
working pH range (4.5-8.0). The sensors show high selectivity in the presence of
some inorganic ions (e.g., PO4(3-), SO4(2-), S2O3(2-), NO2(-), NO3(-), N3(-), CN(
), Cl(-), Br(-), I(-)) and automation feasibility. Indium-porphyrin based
membrane sensor (sensor III) is used as a detector in a wall-jet flow injection
set-up to enable accurate flow injection analysis (FIA) of perchlorate in some
fireworks without interferences from the associated reducing agents (sulfur and
charcoal), binders (dextrin, lactose), coloring agents (calcium, strontium,
copper, iron, sodium), color brighten (linseed oil) and regulators (aluminum
flakes) which are commonly used in the formulations. The sensor is also used for
perchlorate assessment in some propellant powders. The results fairly agree with
data obtained by ion-chromatography.
PMID- 25127584
TI - Ratiometric fluorescent probe for biothiol in aqueous medium with fluorescent
organic nanoparticles.
AB - A dipodal rhodamine-based mercury complex have been designed and synthesized, for
the selective detection of 3-mercaptopropionic acid (MPA). To avoid the poor
solubility of rhodamine-based ligand in pure water, the Hg(2+) complex of
fluorescent organic nanoparticles (FONs) of ligand have been developed using
reprecipitation method and the formation of 1:1 complex has been confirmed with
various spectroscopic techniques. The resultant chemosensor can detect MPA in a
concentration range of 60 nM-1 MUM (in buffered aqueous medium) with detection
limit of 60 nM.
PMID- 25127585
TI - An in-needle extraction technique in determination of organic compounds released
from dental tissue conditioners incubated in artificial saliva.
AB - The use of an in-needle technique for direct isolation of analytes from real
liquid samples is a new proposal. The in-needle technique has been relatively
seldom used for direct sampling of liquid matrix through the needle. In this work
the in-needle technique has been applied for the determination of compounds
evolved to artificial saliva from dental prosthetic materials. It has been shown
that results from the experiment with in-needle device were at least comparable
with those obtained with using well known solid phase extraction (SPE). It is
worth to mention that in-needle extraction offers some advantages: lower
consumption of solvent, shorter step-preparation time and reduced costs. The
compounds released from prosthetic materials may affect the stability of tissue
conditioners and limit their long-term use in the oral cavity. Examined soft
dental materials have been found to be stable as minor amount of various species
have been emitted from them. Results of the stability tests of soft dental
materials with the use of in-needle device on sample preparation step enable
their quick evaluation and estimations of their quality.
PMID- 25127586
TI - A multiclass method for the analysis of endocrine disrupting chemicals in human
urine samples. Sample treatment by dispersive liquid-liquid microextraction.
AB - The population is continuously exposed to endocrine disrupting chemicals (EDCs).
This has influenced an increase in diseases and syndromes that are more frequent
nowadays. Therefore, it is necessary to develop new analytical procedures to
evaluate the exposure with the ultimate objective of establishing, in an accurate
way, relationships between EDCs and harmful health effects. In the present work,
a new method based on a sample treatment by dispersive liquid-liquid
microextraction (DLLME) for the extraction of six parabens (methyl-, ethyl-,
isopropyl-, propyl-, isobutyl and butylparaben), six benzophenones (benzophenone
1, benzophenone-2, benzophenone-3, benzophenone-6, benzophenone-8 and 4
hydroxybenzophenone) and two bisphenols (bisphenol A and bisphenol S) in human
urine samples, followed by gas chromatography-tandem mass spectrometry (GC-MS/MS)
analysis is proposed. An enzymatic treatment allows determining the total content
of the target EDCs. The extraction parameters were accurately optimized using
multivariate optimization strategies. Ethylparaben ring-(13)C6 and bisphenol A
d16 were used as surrogates. Found limits of quantification ranging from 0.2 to
0.5 ng mL(-1) and inter-day variability (evaluated as relative standard
deviation) ranging from 2.0% to 14.9%. The method was validated using matrix
matched standard calibration followed by a recovery assay with spiked samples.
Recovery rates ranged from 94% to 105%. A good linearity, for concentrations up
to 300 ng mL(-1) for parabens and 40 ng mL(-1) for benzophenones and bisphenols,
respectively, was obtained. The method was satisfactorily applied for the
determination of target compounds in human urine samples from 20 randomly
selected individuals.
PMID- 25127587
TI - Ultrasensitive electrochemiluminescent detection of cardiac troponin I based on a
self-enhanced Ru(II) complex.
AB - To promote the luminous efficiency of luminophore, traditional
electrochemiluminescence (ECL) immunoassay usually adopts the adding of
coreactant into testing solution. However, many adverse micro-environmental
factors in the solution are a limiting factor in ECL analytical techniques and
received extensive attention. In our work, a self-enhanced ECL luminophore was
synthesized by combining the coreactant (l-cysteine) and the luminophor (tris
(4,4'-dicarboxylicacid-2,2'-bipyridyl) ruthenium(II) dichloride (Ru(dcbpy)3(2+)))
to form one Ru(II) complex and was applied to fabricate a reagentless
immunosensor for the detection of cardiac troponin I (cTnI) for the first time.
Herein gold nanorods (AuNRs), due to their high specific surface area and good
electrocatalytic ability, were used as carriers for the immobilization of Ru(II)
complex and cTnI antibody to obtain the Ab2 bioconjugates as signal labels. The
application of the self-enhanced Ru(II) complex not only avoided the addition of
any coreactant into testing solution for simplifying the operation, but also
achieved the intramolecular reaction for improving the ECL signal due to shorter
electron transfer path and less energy loss. In view of these advantages, the
proposed immunosensor achieved a wide linear range from 0.25 pg/mL to 0.1 ng/mL
with an impressive detection limit of 0.083 pg/mL for cTnI (S/N=3).
PMID- 25127588
TI - A sensitive and selective colorimetric method for detection of copper ions based
on anti-aggregation of unmodified gold nanoparticles.
AB - A highly sensitive and selective colorimetric method for detection of copper
ions, based on anti-aggregation of D-penicillamine (D-PC) induced aggregated gold
nanoparticles (AuNPs) was developed. Copper ions can hinder the aggregation of
AuNPs induced by D-PC, through formation of mixed-valence complex with D-PC that
is a selective copper chelator. In the presence of a fixed amount of D-PC, the
aggregation of AuNPs decreases with increasing concentrations of Cu(2+) along
with a color change from blue to red in AuNPs solution and an increase in the
absorption ratio (A520/A650). Under the optimum experimental conditions (pH 7,
[AuNPs] =3.0 nmol L(-1) and [NaCl]=25 mmol L(-1)), a linear calibration curve for
Cu(2+) was obtained within the range of 0.05-1.85 umol L(-1) with a limit of
detection (3Sb) of 30 nmol L(-1). Excellent selectivity toward Cu(2+) was
observed among various metal ions due to a specific complex formation between
Cu(2+) and D-PC. The proposed method has been successfully applied for the
detection of Cu(2+) in various real samples.
PMID- 25127589
TI - Application of a fully integrated photodegradation-detection flow-batch analysis
system with an on-line preconcentration step for the determination of metsulfuron
methyl in water samples.
AB - This work presents the development of a fully automated flow-batch analysis (FBA)
system as a new approach for on-line preconcentration, photodegradation and
fluorescence detection in a lab-constructed mixing chamber that was designed to
perform these processes without sample dispersion. The system positions the
mixing chamber into the detection system and varies the instrumental parameters
according to the required photodegradation conditions. The developed FBA system
is simple and easily coupled with any sample pretreatment without altering the
configuration. This FBA system was implemented to photodegrade and determine the
fluorescence of the degradation products of metsulfuron methyl (MSM), a naturally
non-fluorescent herbicide of the sulfonylurea's family. An on-line solid phase
extraction (SPE) and clean up procedure using a C18 minicolumn was coupled to the
photodegradation-detection mixing chamber (PDMC) that was located in the
spectrofluorometer. An enrichment factor of 27 was achieved. Photodegradation
conditions have been optimized by considering the influence of the elution
solvent on both the formation of the photoproduct and on the fluorescence signal.
Under optimal conditions, the calibration for the MSM determination was linear
over the range of 1.00-7.20 ug L(-1). The limit of detection (LOD) was 0.28 ug L(
1); the relative standard deviation was 2.0% and the sample throughput for the
entire process was 3h(-1). The proposed method was applied to real water samples
from the Bahia Blanca's agricultural region (Bahia Blanca, Buenos Aires,
Argentina). This method obtained satisfactory recoveries with a range of 94.7
109.8%.
PMID- 25127590
TI - A two-photon ratiometric fluorescent probe enables spatial coordinates
determination of intracellular pH.
AB - We reported a two-photon ratiometric fluorescent probe for detecting
intracellular pH. When excited with 800 nm laser, an optimal output of laser as
the routine equipment of two-photon fluorescence microscopy, the two-photon
excited fluorescence of this probe showed distinct emission peak shift as large
as 109 nm upon the change of pH values in vitro. Very importantly, the experiment
results show that this probe has large two-photon absorption cross-section at pH
4.5 at 800 nm of 354 g, which ranks it as one of the best two-photon ratiometric
fluorescent pH probes, and its working pH value is between 4.0 and 8.0 which
could fit the intracellular pH range. Moreover, utilizing this probe, the two
photon ratiometric fluorescent images in living cells have been obtained, and the
spatial coordinates of intracellular pH can be mapped. At the same time, the
probe also exhibited selectivity, photostability and membrane permeability. And
the photophysical properties of this probe in various solvents indicated that
these photophysical properties variations are due to an intramolecular charge
transfer process. At last, the imaging depth of the probe in liver biopsy slices
was investigated. The experimental results demonstrated the maximum imaging depth
can arrive 66 um in living rat liver tissues.
PMID- 25127591
TI - Highly sensitive fluorescence quantitative detection of specific DNA sequences
with molecular beacons and nucleic acid dye SYBR Green I.
AB - A highly sensitive fluorescence method of quantitative detection for specific DNA
sequence is developed based on molecular beacon (MB) and nucleic acid dye SYBR
Green I by synchronous fluorescence analysis. It is demonstrated by an
oligonucleotide sequence of wild-type HBV (target DNA) as a model system. In this
strategy, the fluorophore of MB is designed to be 6-carboxyfluorescein group
(FAM), and the maximum excitation wavelength and maximum emission wavelength are
both very close to that of SYBR Green I. In the presence of targets DNA, the MBs
hybridize with the targets DNA and form double-strand DNA (dsDNA), the
fluorophore FAM is separated from the quencher BHQ-1, thus the fluorophore emit
fluorescence. At the same time, SYBR Green I binds to dsDNA, the fluorescence
intensity of SYBR Green I is significantly enhanced. When targets DNA are
detected by synchronous fluorescence analysis, the fluorescence peaks of FAM and
SYBR Green I overlap completely, so the fluorescence signal of system will be
significantly enhanced. Thus, highly sensitive fluorescence quantitative
detection for DNA can be realized. Under the optimum conditions, the total
fluorescence intensity of FAM and SYBR Green I exhibits good linear dependence on
concentration of targets DNA in the range from 2*10(-11) to 2.5*10(-9)M. The
detection limit of target DNA is estimated to be 9*10(-12)M (3sigma). Compared
with previously reported methods of detection DNA with MB, the proposed method
can significantly enhance the detection sensitivity.
PMID- 25127592
TI - Generation of volatile copper species after in situ ionic liquid formation
dispersive liquid-liquid microextraction prior to atomic absorption spectrometric
detection.
AB - The new procedure using in situ synthesis of ionic liquid extractant for
dispersive liquid-liquid microextraction (in situ IL DLLME) combined with
generation of volatile species prior to electrothermal atomic absorption
spectrometry (ET AAS) for the determination of copper in soil samples was
developed. Analytical signals were obtained without the back-extraction of copper
from the IL phase prior to its determination. Under optimal conditions, the
extraction in 10 mL of sample solution employing 8 MUL of 1-hexyl-3
methylimidazolium bis[(trifluoromethyl)sulfonyl]imide (HmimNTf2) (as the
extraction solvent) was conducted. The ionic liquid served as two-task reagent:
the efficient extractant and enhancement substance for generation step. The
chemical generation of volatile species was performed by reduction of acidified
copper solution (HCl 0.8 mol L(-1)) with NaBH4 (1.5%). Some essential parameters
of the chemical generation such as NaBH4 and HCl concentrations, the kind and
concentration of ionic liquid, carrier gas (Ar) flow rate, reaction and trapping
time as well as pyrolysis and atomization temperatures were studied. For
photogeneration the effect of the parameters such as the kind and concentration
of low molecular weight organic acids and ionic liquid, carrier gas (Ar) flow
rate, UV irradiation and ultrasonication time on the analytical signals were
studied. The detection limit was found as 1.8 ng mL(-1) and the relative standard
deviation (RSD) for seven replicate measurements of 100 ug mL(-1) in sample
solution was 7%. The accuracy of the proposed method was evaluated by analysis of
the certified reference materials. The measured copper contents in the reference
materials were in satisfactory agreement with the certified values. The method
was successfully applied to analysis of the soil and sediment samples.
PMID- 25127593
TI - Photochemical sample treatment: a greener approach to chlorobenzene determination
in sediments.
AB - Due to worker's exposure, solvent and stationary phases' consumption, sample
purification is one of the most polluting steps in analytical procedures for
determination of organic pollutants in real samples. The use of photochemical
sample treatment represents a valid alternative methodology for extracts clean up
allowing for a reduction of the used amount of organic solvents. In this paper we
report the first application on the photolytic destruction of organic substances
to eliminate some of the interferences in the analysis of Chlorobenzenes in
sediment samples. The method's efficiency and robustness were compared with
classic silica column purification process currently used in clean up procedures
in sediment analysis. Quality parameters such as recovery, linearity and
reproducibility were studied. The entire procedure was validated by three
replicate analysis of spiked real sediment sample. The quantification limits
(LOQ) obtained by us ranged from 1.0 to 2.3 ng g(-1), while the detection limits
(LOD) were of 1.0 ng g(-1). The RSD for each congener was below 10% and
recoveries were in the range 95-130%. Results based on the analysis of real
samples showed similar or improved detection thresholds and pointed out the
advantages of the photochemical methodology in terms of costs, use of chemical
substances and operator's safety according to Green Analytical Chemistry
principles.
PMID- 25127594
TI - A novel sulfate-reducing bacteria detection method based on inhibition of
cysteine protease activity.
AB - Sulfate-reducing bacteria (SRB) have been extensively studied in corrosion and
environmental science. However, fast enumeration of SRB population is still a
difficult task. This work presents a novel specific SRB detection method based on
inhibition of cysteine protease activity. The hydrolytic activity of cysteine
protease was inhibited by taking advantage of sulfide, the characteristic
metabolic product of SRB, to attack active cysteine thiol group in cysteine
protease catalytic sites. The active thiol S-sulfhydration process could be used
for SRB detection, since the amount of sulfide accumulated in culture medium was
highly related with initial bacterial concentration. The working conditions of
cysteine protease have been optimized to obtain better detection capability, and
the SRB detection performances have been evaluated in this work. The proposed SRB
detection method based on inhibition of cysteine protease activity avoided the
use of biological recognition elements. In addition, compared with the widely
used most probable number (MPN) method which would take up to at least 15days to
accomplish whole detection process, the method based on inhibition of papain
activity could detect SRB in 2 days, with a detection limit of 5.21*10(2) cfu mL(
1). The detection time for SRB population quantitative analysis was greatly
shortened.
PMID- 25127595
TI - Glucose biosensor based on multisegment nanowires exhibiting reversible magnetic
control.
AB - We describe the amperometric detection of glucose using oriented nanowires with
magnetic switching of the bioelectrochemical process. The fabrication process of
the nanowires was prepared through controlled nucleation and growth during a
stepwise electrochemical deposition, and it was characterized using scanning
electron microscopy. Cyclic voltammetry and amperometry were used to study the
magnetoswitchable property; this control was accomplished by changing the surface
orientation of nanowires. Under the optimal condition, the amperometric response
was also linear up to a glucose concentration of 0.1-16.0 mmol L(-1) with a
sensitivity of 81 MUA mM(-1). The detection limit was estimated for 4.8*10(-8)
mol L(-1), defined from a signal/noise ratio of 3. It also exhibits good
reproducibility and high selectivity with insignificant interference from
ascorbic acid, acetoaminophen, and uric acid. The resulting biosensor was applied
to detect the blood sugar in human serum samples without any pretreatment, and
the results were comparatively in agreement with the clinical assay.
PMID- 25127596
TI - Development of aptamer-conjugated magnetic graphene/gold nanoparticle hybrid
nanocomposites for specific enrichment and rapid analysis of thrombin by MALDI
TOF MS.
AB - Simple, rapid and sensitive analysis of thrombin (a tumor biomarker) in complex
samples is quite clinical relevant and essential for the development of disease
diagnosis and pharmacotherapy. Herein, we developed a novel method based on
aptamer-conjugated magnetic graphene/gold nanoparticles nanocomposites (MagG@Au)
for specific enrichment and rapid analysis of thrombin in biological samples
using MALDI-TOF-MS. At first, gold nanoparticles were compactly deposited on PDDA
functionalized magnetic graphene through electrostatic interaction. Afterwards,
aptamer was easily conjugated to gold nanoparticles via Au-S bond formation. The
as-made aptamer-conjugated nanocomposites took advantage of the magnetism of
magnetic graphene, the high affinity and specificity of aptamer, facilitating a
high-efficient separation and enrichment of thrombin. More importantly, due to
the large surface area of the hybrid substrate, the average coverage density of
aptamer achieved 0.34 nmol/mg, which enhanced the thrombin binding capacity and
the recovery of thrombin in real samples. In turn, the enriched thrombin
attributed to the sensitive output of MALDI-TOF mass spectrometry signal, 0.085
ng MUL(-1) (2.36 nM) thrombin could be detected. This proposed method has a
relatively wide linear relation ranging from 0.1 ng MUL(-1) to 10 ng MUL(-1), and
satisfactory specificity. The proposed high-throughput method based on MALDI-TOF
MS is expected to the application in the disease biomarker detection and clinical
diagnosis.
PMID- 25127597
TI - Development of microwave-assisted acid hydrolysis of proteins using a commercial
microwave reactor and its combination with LC-MS for protein full-sequence
analysis.
AB - Microwave-assisted acid hydrolysis (MAAH) can be used to degrade a protein non
specifically into many peptides with overlapping sequences which can be
identified by mass spectrometry (MS) to produce a sequence map that covers the
full sequence of a protein. The success of this method for protein sequence
analysis depends on the proper control of the MAAH process, which is currently
done using a household microwave oven. However, to meet the regulatory or good
laboratory practice (GLP) requirement in a clinical or pharmaceutical laboratory,
using a commercial microwave device is often required. In this paper, we report a
method of performing MAAH using a CEM Discover single-mode microwave reactor. It
is shown that, using an optimized protocol for MAAH, reproducible results
comparable to those obtained using a household microwave oven can be generated
using the commercial reactor. To illustrate the potential applications of MAAH MS
for characterizing clinically relevant proteins, this method was applied, for the
first time, to map the amino acid sequences of normal and sickle-cell human
hemoglobin as well as bovine hemoglobin. Full sequence coverage was readily
achieved from 294 and 266 unique peptides matched to the alpha and beta subunits
of normal hemoglobin, respectively, 334 and 265 unique peptides matched to the
alpha and beta submit units of sickle-cell hemoglobin, and 377 and 224 unique
peptides matched to the alpha and beta subunits of bovine hemoglobin. This method
opens the possibility for any laboratory to use a commercial laboratory equipment
to perform MAAH MS for protein full-sequence analysis.
PMID- 25127598
TI - A cross-reactive sensor array for the fluorescence qualitative analysis of heavy
metal ions.
AB - A cross-reactive sensor array using mercaptopropionic acid modified cadmium
telluride (CdTe), glutathione modified CdTe, poly(methacrylic acid) modified
silver nanoclusters, bovine serum albumin modified gold nanoclusters, rhodamine
derivative and calcein blue as fluorescent indicators has been designed for the
detection of seven heavy metal ions (Ag(+), Hg(2+), Pb(2+), Cu(2+), Cr(3+),
Mn(2+) and Cd(2+)). The discriminatory capacity of the sensor array to different
heavy metal ions in different pH solutions has been tested and the results have
been analyzed with linear discriminant analysis. Results showed that the sensor
array could be used to qualitatively analyze the selected heavy metal ions. The
array performance was also evaluated in the identification of known and unknown
samples and the preliminary results suggested the promising practicability of the
designed sensor assay.
PMID- 25127599
TI - Assessment of robustness on analysis using headspace solid-phase microextraction
and comprehensive two-dimensional gas chromatography through experimental
designs.
AB - Plackett-Burman experimental design was applied for the robustness assessment of
GC*GC-qMS (Comprehensive Two-Dimensional Gas Chromatography with Fast Quadrupolar
Mass Spectrometric Detection) in quantitative and qualitative analysis of
volatiles compounds from chocolate samples isolated by headspace solid-phase
microextraction (HS-SPME). The influence of small changes around the nominal
level of six factors deemed as important on peak areas (carrier gas flow rate,
modulation period, temperature of ionic source, MS photomultiplier power,
injector temperature and interface temperature) and of four factors considered as
potentially influential on spectral quality (minimum and maximum limits of the
scanned mass ranges, ions source temperature and photomultiplier power). The
analytes selected for the study were 2,3,5-trimethylpyrazine, 2-octanone,
octanal, 2-pentyl-furan, 2,3,5,6-tetramethylpyrazine, and 2-nonanone e nonanal.
The factors pointed out as important on the robustness of the system were
photomultiplier power for quantitative analysis and lower limit of mass scanning
range for qualitative analysis.
PMID- 25127600
TI - Continuous sample drop flow-based microextraction method as a microextraction
technique for determination of organic compounds in water sample.
AB - Continuous sample drop flow-based microextraction (CSDF-ME) is an improved
version of continuous-flow microextraction (CFME) and a novel technique developed
for extraction and preconcentration of benzene, toluene, ethyl benzene, m-xylene
and o-xylene (BTEXs) from aqueous samples prior to gas chromatography-flame
ionization detection (GC-FID). In this technique, a small amount (a few
microliters) of organic solvent is transferred to the bottom of a conical bottom
test tube and a few mL of aqueous solution is moved through the organic solvent
at relatively slow flow rate. The aqueous solution transforms into fine droplets
while passing through the organic solvent. After extraction, the enriched analyte
in the extraction solvent is determined by GC-FID. The type of extraction
solvent, its volume, needle diameter, and aqueous sample flow rate were
investigated. The enrichment factor was 221-269 under optimum conditions and the
recovery was 89-102%. The linear ranges and limits of detection for BTEXs were 2
500 and 1.4-3.1 ug L(-1), respectively. The relative standard deviations for 10
ug L(-1) of BTEXs in water were 1.8-6.2% (n=5). The advantages of CSDF-ME are its
low cost, relatively short sample preparation time, low solvent consumption, high
recovery, and high enrichment factor.
PMID- 25127601
TI - Cytochrome P450 2D6 based electrochemical sensor for the determination of
codeine.
AB - Considering the enzymatic activity of the cytochrome P450 2D6 on substrates such
as codeine, the current paper includes the development of an enzymatic biosensor
for detection of this drug. Home-made screen-printed electrodes were used as
electrochemical transducers of the biosensor, in which the enzyme was covalently
attached to the carbon surface of the working electrode, this type of
modification being the most suitable for the immobilization of the biological
element. Chronoamperometric measurements were carried out under optimum
conditions of pH and working potential, pH 7 and +200 mV vs. screen-printed
Ag/AgCl electrode, giving a reduction signal related to the concentration of
codeine in solution. Consecutive additions of a solution of codeine were
performed to obtain calibration curves in order to validate the electrochemical
method in terms of precision and calculate its capability of detection. These
biosensors were used for the determination of codeine in urine and commercial
pharmaceutical samples.
PMID- 25127602
TI - Radical scavenging activity of antioxidants evaluated by means of
electrogenerated HO radical.
AB - A method is proposed and tested concerning the characterization of antioxidants
by means of their reaction with electrogenerated HO radicals in galvanostatic
assays with simultaneous O2 evolution, using a Pt anode fairly oxidized. The
consumption of a set of species with antioxidant activity, ascorbic acid (AA),
caffeic acid (CA), gallic acid (GA) and trolox (T), is described by a first order
kinetics. The rate of the processes is limited by the kinetics of reaction with
HO radicals and by the kinetics of charge transfer. Information regarding the
scavenger activity of antioxidants is obtained by the relative value of the rate
constant of the reaction between antioxidants and HO radicals, k(AO,HO)/k(O2).
The number of HO radicals scavenged per molecule of antioxidant is also estimated
and ranged from 260 (ascorbic acid) to 500 (gallic acid). The method is applied
successfully in the characterization of the scavenger activity of ascorbic acid
in a green-tea based beverage.
PMID- 25127604
TI - Towards a non-invasive quantitative analysis of the organic components in museum
objects varnishes by vibrational spectroscopies: methodological approach.
AB - The compositions of ancient varnishes are mainly determined destructively by
separation methods coupled to mass spectrometry. In this study, a methodology for
non-invasive quantitative analyses of varnishes by vibrational spectroscopies is
proposed. For that, experimental simplified varnishes of colophony and linseed
oil were prepared according to 18th century traditional recipes with an
increasing mass concentration ratio of colophony/linseed oil. FT-Raman and IR
analyses using ATR and non-invasive reflectance modes were done on the "pure"
materials and on the different mixtures. Then, a new approach involving spectral
decomposition calculation was developed considering the mixture spectra as a
linear combination of the pure materials ones, and giving a relative amount of
each component. Specific spectral regions were treated and the obtained results
show a good accuracy between the prepared and calculated amounts of the two
compounds. We were thus able to detect and quantify from 10% to 50% of colophony
in linseed oil using non-invasive techniques that can also be conducted in situ
with portable instruments when it comes to museum varnished objects and
artifacts.
PMID- 25127603
TI - Amplified electrochemical detection of protein kinase activity based on gold
nanoparticles/multi-walled carbon nanotubes nanohybrids.
AB - A sensitive and simple electrochemical strategy has been developed for assay of
protein kinase A (PKA) activity and inhibition using gold nanoparticles/multi
walled carbon nanotubes (AuNPs/MWNTs) nanohybrids. Key features of this assay
included intrinsic peroxidase-like activity of positively-charged gold
nanoparticles (+AuNPs) and signal transduction and amplification of multi-walled
carbon nanotubes (MWNTs). In this assay, an N-terminally cysteine-containing
peptide was self-assembled onto the gold electrode via Au-S bonding and used as
substrate for PKA, and adenosine-5'-(gamma-thio)-triphosphate was used as co
substrate. Upon thiophosphorylation in the presence of PKA, the AuNPs/MWNTs
nanohybrids would be fixed onto the peptides via Au-S bond. The conjugated
AuNPs/MWNTs nanohybrids could catalyze the 3, 3', 5, 5'-Tetramethylbenzidine
(TMB) oxidation by H2O2 to form TMB oxidation product, which was reduced at the
electrode surface to generate an electrochemical current. It was eT on state. The
current signal intensity is proportional to the activity of PKA. Here, the
presence of MWNTs not only increased the surface area for accumulation of +AuNPs
but also could promote electron-transfer reaction. It was found that the
electrochemical strategy can be employed to assay PKA activity with a low
detection limit of 0.09 U/mL. The linear range of the assay for PKA enzymatic
unit/ml was 0.1-1 U/mL. Furthermore, the interferences experiments of T4
polynucleotide kinase (T4 PNK) and Casein kinase II (CK2), and inhibition of PKA,
have also been studied by using this strategy. The developed method would provide
a diversified platform for kinase activity and inhibition monitoring.
PMID- 25127605
TI - A new voltammetric sensor for sensitive and selective determination of xanthine
based on DNA and polyaniline composite Langmuir-Blodgett film.
AB - DNA-polyaniline (PAn) complex Langmuir-Blodgett film modified glassy carbon
electrode (GCE) was used as a new voltammetric sensor (DNA/PAn-LB/GCE) for
xanthine (XA) detection. The characteristic of DNA/PAn-LB film was studied by
electrochemical impedance spectroscopy and scanning electron microscope.
Electrochemical behaviors of XA at the sensor were studied in pH 7.0 phosphate
buffer solutions by cyclic voltammetry and differential pulse anodic voltammetry.
The results showed that this new modified electrode exhibited an excellent
immunity from uric acid and hypoxanthine interference and a new sensitive and
selective electroanalytical method for XA was proposed with wider linear range.
Under the optimum conditions, the calibration curve for XA was obtained over the
range of 7.0*10(-8)-1.0*10(-5) mol L(-1), with the detection limit of 3.0*10(-8)
mol L(-1). The practicability of this method was demonstrated by determining the
concentration of XA in human serum samples.
PMID- 25127606
TI - Development, optimization and validation of a multimethod for the determination
of 36 mycotoxins in wines by liquid chromatography-tandem mass spectrometry.
AB - A fast and efficient multimethod for the determination of 36 mycotoxins in wine,
using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC
MS/MS), was developed, optimized, validated and implemented in routine analysis.
A simplified, quick extraction was performed with acetonitrile, derived from the
QuEChERS (quick, easy, cheap, effective, rugged and safe) approach, which was
traditionally developed for pesticides analysis. This study aimed at a single
extraction and chromatographic separation for 36 mycotoxins. Optimization tests
were performed to find the proper ratio of wine: water and extraction solvent and
the need for an additional buffering step with ammonium formate/formic acid and a
dispersive SPE cleanup with various sorbents. The dSPE steps did not show
significant improvement in analysis results, therefore, it was not applied in the
final method to be validated. The mycotoxins were separated and detected on a
UPLC-MS/MS system, used in the ESI positive ionization mode. The various
mycotoxins were divided in three different concentration level groups, according
to their sensitivity in UPLC-MS/MS. The validation was performed by analyzing
recovery samples at three different spike levels with six replicates (n=6) at
each level. Linearity (r(2)) of calibration curves, accuracy (recovery %),
instrument limits of detection and method limits of quantification (LOD and LOQ),
precision (RSD%) and matrix effects (%) were determined for each individual
mycotoxin. From the 36 mycotoxins analyzed by UPLC-MS/MS (ESI+), 35 showed
average recoveries in the range 70-120%, and 86% of these with a RSD<=20% at the
lowest spike level (for Group I, II and III, respectively, 1, 50 and 10 ug kg(
1)). The higher spike levels showed even better results. Only nivalenol could not
be quantified at any concentration level. The method LOQ for 86% of the
mycotoxins studied was the lowest spike level tested. The matrix effect observed
was low for most mycotoxins analyzed and had no significant influence on the
analytical results obtained. The developed procedure was applied successfully in
routine analysis in a survey of wine samples originating from different
countries.
PMID- 25127607
TI - The QuEChERS approach in a novel application for the identification of antifungal
compounds produced by lactic acid bacteria cultures.
AB - Lactic Acid Bacteria (LAB) play an important role as natural food preservatives
in many fermented food systems. To-date, characterisation of their diverse range
of metabolites has been limited. Improved quantitation of low, medium and high
concentration antifungal compounds is required, ensuring that both known and
unknowns compounds are identified. This manuscript reports the first application
of QuEChERS (quick, easy, cheap, effective, rugged and safe) for the extraction
of natural antifungal metabolites in LAB cultures. The method provides improved
individual recoveries (>78%) for 15 known antifungal compounds, an improvement of
26% compared to previously reported techniques (>52%). A protocol was developed
that allowed LAB cultures to be easily assessed on a fully validated high
performance liquid chromatography with ultra violet/diode array detection (HPLC
UV/DAD) method. Previously reported methods involving direct injection of
filtered extracts and SPE clean-up, suffered from a rise in chromatographic
baseline due to interfering matrix components, limiting accurate quantitation.
This QuEChERS method removed these interfering matrix components to deliver clean
chromatograms with greater recoveries (78.2-127.4%) and lower RSD values (2.5
10.8%) of all 15 antifungal compounds. The validated method was applied to LAB
strains showing particularly strong antifungal activity and provided an increase
in the number of compounds detected (both known and unknown) compared to previous
techniques for the same strains, due to the improved recoveries now possible by
this method. Confirmation of the compounds identified was performed by analysis
on a liquid chromatography linear ion trap quadrupole Orbitrap hybrid Fourier
transform mass spectrometer (LC-FTMS). This first application of QuEChERS to LAB
cultures has significantly improved the analytical capabilities of antifungal
compound profiling especially where the synergy of numerous compounds is
suspected as producing the observed activity. LAB cultures can now be easily
integrated into various food matrices, as natural food preservatives, now that a
complete analyte profile is achievable.
PMID- 25127609
TI - Simultaneous voltammetric determination of paracetamol and ascorbic acid using a
boron-doped diamond electrode modified with Nafion and lead films.
AB - The paper describes the fabrication and application of a novel sensor (a boron
doped diamond electrode modified with Nafion and lead films) for the simultaneous
determination of paracetamol and ascorbic acid by differential pulse voltammetry.
The main advantage of the lead film and polymer covered boron-doped diamond
electrode is that the sensitivity of the stripping responses is increased and the
separation of paracetamol and ascorbic acid signals is improved due to the
modification of the boron-doped diamond surface by the lead layer. Additionally,
the repeatability of paracetamol and ascorbic acid signals is improved by the
application of the Nafion film coating. In the presence of oxygen, linear
calibration curves were obtained in a wide concentration range from 5*10(-7) to
2*10(-4) mol L(-1) for paracetamol and from 1*10(-6) to 5*10(-4) mol L(-1) for
ascorbic acid. The analytical utility of the differential pulse voltammetric
method elaborated was tested in the assay of paracetamol and ascorbic acid in
commercially available pharmaceutical formulations and the method was validated
by high performance liquid chromatography coupled with diode array detector.
PMID- 25127610
TI - Optimization of the in-needle extraction device for the direct flow of the liquid
sample through the sorbent layer.
AB - In-needle extraction was applied for preparation of aqueous samples. This
technique was used for direct isolation of analytes from liquid samples which was
achieved by forcing the flow of the sample through the sorbent layer: silica or
polymer (styrene/divinylbenzene). Specially designed needle was packed with three
different sorbents on which the analytes (phenol, p-benzoquinone, 4-chlorophenol,
thymol and caffeine) were retained. Acceptable sampling conditions for direct
analysis of liquid sample were selected. Experimental data collected from the
series of liquid samples analysis made with use of in-needle device showed that
the effectiveness of the system depends on various parameters such as
breakthrough volume and the sorption capacity, effect of sampling flow rate,
solvent effect on elution step, required volume of solvent for elution step. The
optimal sampling flow rate was in range of 0.5-2 mL/min, the minimum volume of
solvent was at 400 uL level.
PMID- 25127608
TI - A simple, fast and cheap non-SPE screening method for antibacterial residue
analysis in milk and liver using liquid chromatography-tandem mass spectrometry.
AB - In routine laboratory work, screening methods for multiclass analysis can process
a large number of samples in a short time. The main challenge is to develop a
methodology to detect as many different classes of residues as possible, combined
with speed and low cost. An efficient technique for the analysis of multiclass
antibacterial residues (fluoroquinolones, tetracyclines, sulfonamides and
trimethoprim) was developed based on simple, environment-friendly extraction for
bovine milk, cattle and poultry liver. Acidified ethanol was used as an
extracting solvent for milk samples. Liver samples were treated using EDTA-washed
sand for cell disruption, methanol:water and acidified acetonitrile as extracting
solvent. A total of 24 antibacterial residues were detected and confirmed using
liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), at levels
between 10, 25 and 50% of the maximum residue limit (MRL). For liver samples a
metabolite (sulfaquinoxaline-OH) was also monitored. A validation procedure was
conducted for screening purposes in accordance with European Union requirements
(2002/657/EC). The detection capability (CCbeta) false compliant rate was less
than 5% at the lowest level for each residue. Specificity and ruggedness were
also discussed. Incurred and routine samples were analyzed and the method was
successfully applied. The results proved that this method can be an important
tool in routine analysis, since it is very fast and reliable.
PMID- 25127611
TI - Dual hairpin-like molecular beacon based on coralyne-adenosine interaction for
sensing melamine in dairy products.
AB - This study presents a novel dual hairpin-like molecular beacon (MB) for the
selective and sensitive detection of melamine (MA) based on the conjugation of MA
and thymine. In this protocol, the coordination between coralyne and adenosine
(A) leaded a dual hairpin-like MB and the fluorophore-quencher pair is close
proximity resulting in the fluorescence quenching. With the addition of MA, it
conjugated with thymine in the loop part of dual hairpin-like MB by triple H
bonds, triggering the dissociation of the dual hairpin-like MB. The resulting
spatial separation of the fluorophore from quencher induced the enhancement in
fluorescence emission. Under the optimized conditions, the sensor exhibited a
wide linear range of 8*10(-9)-1.6*10(-5) M (R(2)=0.9969) towards MA, with a low
detection limit of 5 nM, approximately 4000 times lower than the Drug
Administration and the US Food estimated MA safety limit. The real milk samples
were also investigated with a satisfying result.
PMID- 25127612
TI - Microwave assisted extraction-solid phase extraction for high-efficient and rapid
analysis of monosaccharides in plants.
AB - Monosaccharides are the fundamental composition units of saccharides which are a
common source of energy for metabolism. An effective and simple method consisting
of microwave assisted extraction (MAE), solid phase extraction (SPE) and high
performance liquid chromatography-refractive index detector (HPLC-RID) was
developed for rapid detection of monosaccharides in plants. The MAE was applied
to break down the structure of the plant cells and release the monosaccharides,
while the SPE procedure was adopted to purify the extract before analysis.
Finally, the HPLC-RID was employed to separate and analyze the monosaccharides
with amino column. As a result, the extraction time was reduced to 17 min, which
was nearly 85 times faster than soxhlet extraction. The recoveries of arabinose,
xylose, fructose and glucose were 85.01%, 87.79%, 103.17%, and 101.24%, with
excellent relative standard deviations (RSDs) of 1.94%, 1.13%, 0.60% and 1.67%,
respectively. The proposed method was demonstrated to be efficient and time
saving, and had been applied to analyze monosaccharides in tobacco and tea
successfully.
PMID- 25127613
TI - Facile fabrication of an ultrasensitive sandwich-type electrochemical
immunosensor for the quantitative detection of alpha fetoprotein using
multifunctional mesoporous silica as platform and label for signal amplification.
AB - A novel and ultrasensitive sandwich-type electrochemical immunosensor was
designed for the quantitative detection of alpha fetoprotein (AFP) using
multifunctional mesoporous silica (MCM-41) as platform and label for signal
amplification. MCM-41 has high specific surface area, high pore volume, large
density of surface silanol groups (SiOH) and good biocompatibility. MCM-41
functionalized with 3-aminopropyltriethoxysilane (APTES), gold nanoparticles (Au
NPs) and toluidine blue (TB) could enhance electrochemical signals. Moreover,
primary antibodies (Ab1) and secondary antibodies (Ab2) could be effectively
immobilized onto the multifunctional MCM-41 by the interaction between Au NPs and
amino groups (-NH2) on antibodies. Using multifunctional MCM-41 as a platform and
label could greatly simplify the fabrication process and result in a high
sensitivity of the designed immunosensor. Under optimal conditions, the designed
immunosensor exhibited a wide liner range from 10(-4) ng/mL to 10(3) ng/mL with a
low detection limit of 0.05 pg/mL for AFP. The designed immunosensor showed
acceptable selectivity, reproducibility and stability, which could provide
potential applications in clinical monitoring of AFP.
PMID- 25127614
TI - Determination of mercury in river water by diffusive gradients in thin films
using P81 membrane as binding layer.
AB - In this work, a device based on diffusive gradients in thin films (DGT) was
evaluated for the determination of Hg(II) in river water. The DGT device was
assembled with a cellulose phosphate ion exchange membrane (P81 Whatman) as a
binding phase and agarose gel 1.5% (m/v) as a diffusive layer. Laboratory
deployments showed that the binding of Hg(2+) ([Hg(DGT)]/[Hg(solution)]) by P81
membrane was more effective (97%) than the Chelex 100 resin (80%).The effect of
ionic strength, pH and potential interfering ions on Hg binding with DGT's was
investigated. The results showed no significant effect on the binding of Hg(II)
at pH range from 3.5 to 8.5 and at an ionic strength range from 0.0005 to 0.1 mol
L(-1). Uptakes of 50 ug L(-1) Hg(II) by P81 membrane were not affected by Fe, Mn,
Zn, Cu, Ca and Mg at the concentration range of 200-1800 ug L(-1). Finally, the
DGT device using the P81 as the binding layer was applied for in situ
measurements of Hg in river water. For in situ measurements, the labile Hg
concentration (from <2 to 13 ng L(-1)) was lower than 10% of the dissolved
fraction (from 155 to 446 ng L(-1)).
PMID- 25127616
TI - Sulfonated polystyrene magnetic nanobeads coupled with immunochromatographic
strip for clenbuterol determination in pork muscle.
AB - A magnetic solid-phase extraction method (MSPE) was developed to pre-concentrate
and cleanup clenbuterol (CLE) from pork muscle. Novel sulfonated polystyrene
magnetic nanobeads (spMNBs) were synthesized via a one-pot emulsion
copolymerization method by using divinylbenzene, styrene, and sodium styrene
sulfonate in the presence of oleic acid-modified and 10-undecylenic acid-modified
magnetic ferrofluid. The resulting spMNBs exhibited high adsorption efficiency
for CLE and for 10 other common beta-adrenergic agonists, namely, brombuterol,
ractopamine, tulobuterol, bambuterol, cimbuterol, mabuterol, clorprenaline,
penbutolol, salbutamol, and cimaterol. The adsorption behavior of the spMNBs for
CLE was described by the Langmuir equation with a maximum adsorption capacity of
0.41 mg/g. Under the optimized parameters, the extraction of CLE from 0.5 g of
pork muscle required 25mg of the spMNBs at a shortened adsorption time (0.5 min).
The proposed MSPE was coupled with colloidal gold nanoparticle-based
immunochromatographic assay (MSPE-AuNPIA) for the quantitative detection of CLE
residue in pork muscle. The limit of detection and limit of quantification for
the pork muscle were 0.10 and 0.24 ng/g, respectively. The intra-day and inter
day assay recoveries at three CLE spiked concentrations ranged from 92.5% to
98.1%, with relative standard deviations ranging from 3.2% to 13.0%. The results
of MSPE-AuNPIA were confirmed by liquid chromatography-tandem mass spectrometry
(LC-MS/MS). The CLE values obtained with MSPE-AuNPIA agreed with those obtained
with LC-MS/MS.
PMID- 25127617
TI - Investigation on performance of zirconia and magnesia-zirconia stationary phases
in hydrophilic interaction chromatography.
AB - In the current study, zirconia (ZrO2) and its composite, magnesia-zirconia (MgO
ZrO2), were prepared as the hydrophilic interaction chromatographic (HILIC)
stationary phases (SPs). Different experimental variables including water
content, pH and buffer concentration in the mobile phase (MP) as well as column
temperature were systematically studied to permit an in-depth understanding of
the chromatographic properties of the mentioned SPs and to explore the retention
mechanism further on. The results were compared with a native SiO2 column.
Adsorption was demonstrated as the main retention mechanism on the two ZrO2-based
SPs. The transferring of the analytes from the MP to the ZrO2-based SPs was
endothermic and high column temperature would facilitate the retention. In
addition, the MgO-ZrO2 SP exhibited superior resolution, column efficiency as
well as stronger retention in comparison to the bare ZrO2 SP, which demonstrated
that the introduction of MgO could improve the structure and properties of the
material. In conclusion, MgO-ZrO2 was a promising material for HILIC
applications.
PMID- 25127615
TI - Detection of potato brown rot and ring rot by electronic nose: from laboratory to
real scale.
AB - A commercial electronic nose (e-nose) equipped with a metal oxide sensor array
was trained to recognize volatile compounds emitted by potatoes experimentally
infected with Ralstonia solanacearum or Clavibacter michiganensis subsp.
sepedonicus, which are bacterial agents of potato brown and ring rot,
respectively. Two sampling procedures for volatile compounds were tested on
pooled tubers sealed in 0.5-1 L jars at room temperature (laboratory conditions):
an enrichment unit containing different adsorbent materials (namely, Tenax((r))
TA, Carbotrap, Tenax((r)) GR, and Carboxen 569) directly coupled with the e-nose
(active sampling) and a Radiello(TM) cartridge (passive sampling) containing a
generic Carbograph fiber. Tenax((r)) TA resulted the most suitable adsorbent
material for active sampling. Linear discriminant analysis (LDA) correctly
classified 57.4 and 81.3% total samples as healthy or diseased, when using active
and passive sampling, respectively. These results suggested the use of passive
sampling to discriminate healthy from diseased tubers under intermediate and real
scale conditions. 80 and 90% total samples were correctly classified by LDA under
intermediate (100 tubers stored at 4 degrees C in net bag passively sampled) and
real scale conditions (tubers stored at 4 degrees C in 1.25 t bags passively
sampled). Principal component analysis (PCA) of sensorial analysis data under
laboratory conditions highlighted a strict relationship between the disease
severity and the responses of the e-nose sensors, whose sensitivity threshold was
linked to the presence of at least one tuber per sample showing medium disease
symptoms. At intermediate and real scale conditions, data distribution agreed
with disease incidence (percentage of diseased tubers), owing to the low storage
temperature and volatile compounds unconfinement conditions adopted.
PMID- 25127618
TI - Analytical methods for the determination of personal care products in human
samples: an overview.
AB - Personal care products (PCPs) are organic chemicals widely used in everyday human
life. Nowadays, preservatives, UV-filters, antimicrobials and musk fragrances are
widely used PCPs. Different studies have shown that some of these compounds can
cause adverse health effects, such as genotoxicity, which could even lead to
mutagenic or carcinogenic effects, or estrogenicity because of their endocrine
disruption activity. Due to the absence of official monitoring protocols, there
is an increasing demand of analytical methods that allow the determination of
those compounds in human samples in order to obtain more information regarding
their behavior and fate in the human body. The complexity of the biological
matrices and the low concentration levels of these compounds make necessary the
use of advanced sample treatment procedures that afford both, sample clean-up, to
remove potentially interfering matrix components, as well as the concentration of
analytes. In the present work, a review of the more recent analytical methods
published in the scientific literature for the determination of PCPs in human
fluids and tissue samples, is presented. The work focused on sample preparation
and the analytical techniques employed.
PMID- 25127619
TI - First use of portable system coupling X-ray diffraction and X-ray fluorescence
for in-situ analysis of prehistoric rock art.
AB - Study of prehistoric art is playing a major role in the knowledge of human
evolution. Many scientific methods are involved in this investigation including
chemical analysis of pigments present on artefacts or applied to cave walls. In
the past decades, the characterization of coloured materials was carried on by
taking small samples. This procedure had two main disadvantages: slight but
existing damage of the paintings and limitation of the number of samples. Thanks
to the advanced development of portable systems, in-situ analysis of pigment in
cave can be now undertaken without fear for this fragile Cultural Heritage. For
the first time, a portable system combining XRD and XRF was used in an
underground and archaeological environment for prehistoric rock art studies. In
situ non-destructive analysis of black prehistoric drawings and determination of
their composition and crystalline structure were successfully carried out.
Original results on pigments used 13,000 years ago in the cave of Rouffignac
(France) were obtained showing the use of two main manganese oxides: pyrolusite
and romanechite. The capabilities of the portable XRD-XRF system have been
demonstrated for the characterization of pigments as well as for the analysis of
rock in a cave environment. This first in-situ experiment combining X-ray
diffraction and X-ray fluorescence open up new horizons and can fundamentally
change our approach of rock art studies.
PMID- 25127620
TI - A novel restricted access material combined to molecularly imprinted polymers for
selective solid-phase extraction and high performance liquid chromatography
determination of 2-methoxyestradiol in plasma samples.
AB - A feasibility study was performed in order to ensure the possibilities in using a
restricted access material combined to molecularly imprinted polymers (RAM-MIP)
as sorbent material in solid phase extraction (SPE) for clean-up of 2
methoxyestradiol (2-ME) from plasma samples. The MIP with hydrophilic external
layer was designed by precipitation polymerization. The polymer was characterized
by thermogravimetric analysis (TGA) and scanning electron microscope (SEM). The
use of analogs of 2-ME as templates, in combination with a chromatographic
separation of the analytes in the sample, overcame the problem of the template
bleeding. To demonstrate the property of the RAM-MIP obtained, a comparison of
commercially available C18 SPE was performed. The results showed that the RAM
MISPE recoveries were significantly higher than that of C18 SPE for 2-ME in trace
concentration. During the extraction process, 2-ME was sufficiently cleaned for
further chromatographic analysis with no interferences from template leakage and
matrix. Good linearity was obtained from 0.06 to 20 MUg mL(-1) with the
correlation coefficient r>0.9991. The coefficient of variation of the inter-assay
precision was less than 11.9%. The recoveries of 2-ME in rat plasma at three
spiked levels were in the range of 99.10-101.00%. Based on the analytical
validation results, the proposed method (RAM-MIP off-line SPE/HPLC) can be a
useful tool to determine 2-ME in rat plasma samples.
PMID- 25127621
TI - Application of multivariate chemometric techniques for simultaneous determination
of five parameters of cottonseed oil by single bounce attenuated total
reflectance Fourier transform infrared spectroscopy.
AB - Single bounce attenuated total reflectance (SB-ATR) Fourier transform infrared
(FTIR) spectroscopy in conjunction with chemometrics was used for accurate
determination of free fatty acid (FFA), peroxide value (PV), iodine value (IV),
conjugated diene (CD) and conjugated triene (CT) of cottonseed oil (CSO) during
potato chips frying. Partial least square (PLS), stepwise multiple linear
regression (SMLR), principal component regression (PCR) and simple Beer's law
(SBL) were applied to develop the calibrations for simultaneous evaluation of
five stated parameters of cottonseed oil (CSO) during frying of French frozen
potato chips at 170 degrees C. Good regression coefficients (R(2)) were achieved
for FFA, PV, IV, CD and CT with value of >0.992 by PLS, SMLR, PCR, and SBL. Root
mean square error of prediction (RMSEP) was found to be less than 1.95% for all
determinations. Result of the study indicated that SB-ATR FTIR in combination
with multivariate chemometrics could be used for accurate and simultaneous
determination of different parameters during the frying process without using any
toxic organic solvent.
PMID- 25127622
TI - Measurement of U and Pu isotope ratios in hair and nail samples using extraction
chromatography and multi-collector inductively coupled plasma mass spectrometry.
AB - A bioassay capable of monitoring occupational or environmental exposure to
special nuclear materials would be a useful tool for nuclear nonproliferation
programs. Hair and nail are potential biomonitors of exposure to U and Pu. A
method is described to measure isotope ratios of ultra-trace concentrations of U
and Pu in hair and nail samples. The method uses multiple extraction
chromatography resins to separate U and Pu fractions from the sample matrix. The
U recovery was quantitative while the Pu recovery ranged from 81% to 109%, with a
U decontamination factor of 5*10(4). Following the separation (234)U/(238)U,
(235)U/(238)U and (240)Pu/(239)Pu were measured in human hair and hair and nail
samples using multi-collector inductively coupled plasma mass spectrometry (MC
ICPMS). The human hair and nail samples had elevated ratios of (234)U/(238)U
which could reflect exposure to naturally fractionated U.
PMID- 25127623
TI - Comparison of different types of diffusive gradient in thin film samplers for
measurement of dissolved methylmercury in freshwaters.
AB - Determination of bioavailable concentrations of methylmercury (MeHg(+)) in
freshwater is key to further understanding its potential risk and toxicity. In
this work, two in-house-manufactured mercury-specific diffusive gradients in thin
films (DGT) were used in laboratory to assess the lability of MeHg(+), and to
develop a relationship between chemical lability and bioavailability. After
diffusing through the diffusive gel, the MeHg(+) accumulated in a thiol
functionalised resin gel was extracted using acidic thiourea that was analysed
using aqueous-phase propylation followed by headspace solid-phase microextraction
(HS-SPME) and gas chromatography (GC) coupled to pyrolysis-atomic fluorescence
spectrometry (Py-AFS) detection. The diffusion coefficient (D) at 25 degrees C in
agarose (A-DGT) in the absence and presence of dissolved organic matter (DOM) was
obtained. Moreover, these values were experimentally compared against
polyacrylamide (P-DGT), which is the most frequently used DGT for mercury to
date. Statistically significant differences were observed between D values for A
DGT in the absence (3.15*10(-6) cm(2) s(-1)) and presence of DOM (2.68*10(-6)
cm(2) s(-1)) and also for P-DGT (2.49*10(-6) and 1.69*10(-6) cm(2) s(-1)).
Interestingly, our results show that diffusion of MeHg(+) was higher on agarose
diffusive gel with and without DOM in comparison with those observed in
polyacrylamide. Even with higher diffusion coefficients of MeHg(+) in the agarose
diffusion layer, however, DGT based on polyacrylamide seems to be a better choice
for eutrophic waters, when monitoring very low concentrations of MeHg(+),
considering its slightly higher uptake capacity.
PMID- 25127624
TI - Low cost microfluidic cell culture array using normally closed valves for
cytotoxicity assay.
AB - A reusable low cost microfluidic cell culture array device (MCCAD) integrated
with a six output concentration gradient generator (cGG) and 4*6 arrays of
microchamber elements, addressed by a series of row and columnar pneumatically
actuated normally closed (NC) microvalves was fabricated for cell-based screening
of chemotherapeutic compounds. The poly(dimethylsiloxane) (PDMS) device consists
of three layers: fluidic, control and membrane which are held by surface contact
and made leak-proof by clamping pressure. The NC valves are actuated by a thick
PDMS membrane that was created by a novel method based on the self-assembly of
PDMS pre-polymer molecules over a denser calcium chloride solution. The membrane
actuated the valves reliably and particulates such as alumina particles (3 um)
and MCF-7 cells (20-24 um) (2*10(5) cells/mL) were flowed through the valves
without causing blockage or leakage and consequently avoiding contamination of
the different cell culture elements. The MCCAD was cast and assembled in a
standard laboratory without specialist equipment and demonstrated for performing
quantitative cell-based cytotoxicity assays of pyocyanine on human breast cancer
(MCF-7) cells and assessed for toxic effect on human hepatocyte carcinoma (HepG2)
cells as an indicator for liver injury. Then, the MCCAD was demonstrated for
sequential drug combinatorial screening involving gradient generation of
paclitaxel doses followed by treatment with aspirin doses on the viability of MCF
7 cells. The interaction between paclitaxel and aspirin was evaluated by using
the Bliss independence predictive model and results showed reasonable agreement
with the model. A robust, portable, easily fabricated and low cost device is
therefore shown to conveniently carry out culturing of multiple cell lines for
high throughput screening of anti-cancer compounds using minimal reagents.
PMID- 25127625
TI - Application of neodymium isotope ratio measurements for the origin assessment of
uranium ore concentrates.
AB - A novel procedure has been developed for the measurement of (143)Nd/(144)Nd
isotope ratio in various uranium-bearing materials, such as uranium ores and ore
concentrates (UOC) in order to evaluate the usefulness and applicability of
variations of (143)Nd/(144)Nd isotope ratio for provenance assessment in nuclear
forensics. Neodymium was separated and pre-concentrated by extraction
chromatography and then the isotope ratios were measured by multi-collector
inductively coupled plasma mass spectrometry (MC-ICP-MS). The method was
validated by the measurement of standard reference materials (La Jolla, JB-2 and
BCR-2) and the applicability of the procedure was demonstrated by the analysis of
uranium samples of world-wide origin. The investigated samples show distinct
(143)Nd/(144)Nd ratio depending on the ore type, deposit age and Sm/Nd ratio.
Together with other characteristics of the material in question, the Nd isotope
ratio is a promising signature for nuclear forensics and suggests being
indicative of the source material, the uranium ore.
PMID- 25127626
TI - Assessment of gas chromatography time-of-flight accurate mass spectrometry for
identification of volatile and semi-volatile compounds in honey.
AB - The performance of gas chromatography (GC) combined with a hybrid quadrupole time
of-flight (QTOF) mass spectrometry (MS) system for the determination of volatile
and semi-volatile compounds in honey samples is evaluated. After headspace (HS)
solid-phase microextraction (SPME) of samples, the accurate mass capabilities of
the above system were evaluated for compounds identification. Accurate scan
electron impact (EI) MS spectra allowed discriminating compounds displaying the
same nominal masses, but having different empirical formulae. Moreover, the use
of a mass window with a width of 0.005 Da provided highly specific chromatograms
for selected ions, avoiding the contribution of interferences to their peak
areas. Additional information derived from positive chemical ionization (PCI) MS
spectra and ion product scan MS/MS spectra permitted confirming the identity of
novel compounds. The above possibilities are illustrated with examples of honey
aroma compounds, belonging to different chemical classes and containing different
elements in their molecules. Examples of compounds whose structures could not be
described are also provided. Overall, 84 compounds, from a total of 89 species,
could be identified in 19 honey samples from 3 different geographic areas in the
world. The suitability of responses measured for selected ions, corresponding to
above species, for authentication purposes is assessed through principal
components analysis.
PMID- 25127627
TI - Fluorescence method using on-line sodium cholate coacervate surfactant mediated
extraction for the flow injections analysis of Rhodamine B.
AB - An on-line surfactant mediated extraction method in a flow injection analysis
format with fluorescence detection was developed for the determination of
Rhodamine B (RhB) in food condiments. The sample was extracted using the phase
separation behavior exhibited by the bile salt surfactant, sodium cholate (NaC),
upon addition of sodium dodecylsulfate (SDS) in the presence of acid at room
temperature. The RhB in the sample was incorporated into the NaC/SDS coacervate
phase which was then collected on a glass-wool packed mini column from which it
was subsequently eluted using a 1.00 mol L(-1) HCl solution. The inherent
fluorescence (lambdaex=555 nm; lambdaem=575 nm) of RhB was employed for
detection. Good linearity (r(2)=0.9933) was obtained over the concentration range
0.4-4794-479.0 ug L(-1) RhB. The detection (LOD) and quantification (LOQ) limits
were 0.12 and 0.40 ug L(-1), respectively. The method was successfully applied
for analysis of RhB in food condiments and spiked samples. The average recoveries
ranged from 95.3% to 118.9% at spiked concentration levels of 1.19 and 2.39 ug L(
1). Under optimized conditions, a throughput of 50 samples per hour was achieved.
The proposed method may be a valuable tool not only for quality control of food
condiments and similar food confectioneries but for the analysis of a variety of
other RhB-containing samples as well.
PMID- 25127628
TI - Gr-Pt hybrid NP modified GCPE as label and indicator free electrochemical
genosensor platform.
AB - Glassy carbon paste electrode (GCPE) was modified with graphene platinum hybrid
nanoparticle (Gr-Pt hybrid NP) and used as a transducer for label and indicator
free electrochemical genosensor. 22 mer oligonucleotides representing Escherichia
coli bacteria were used as a model case. As far as it is known, this study is the
first study where Gr-Pt hybrid NP was incorporated into GCPE and used for
genosensor transducer. The extent of hybridization was determined by using
differential pulse voltammetric signals of guanin oxidation. After the
optimization of experimental parameters, analytical characteristics were
investigated. The linear range was found between 1.5*10(-7) and 2.25*10(-6) M
with the equation of y=1.6566x-2.6161 and R(2) of 0.9959. RSD and LOD were
calculated as 4.2% (n=6) and 1.12*10(-9) M respectively.
PMID- 25127629
TI - High-performance liquid chromatographic and mass spectrometric analysis of
fluorescent carbon nanodots.
AB - Amino/hydroxyl-functionalized fluorescent carbon nanodots (C-NanoD) are
conveniently synthesized based on hydrothermal carbonization of chitosan at 180
degrees C. Dialysis membranes with small cut-off masses (500-1000 Da) were found
useful for removing the side-products and low molecular mass species to purify
the C-NanoD product. Herein, reversed-phase high-performance liquid
chromatography (RP-HPLC) has been successfully applied to fractionate the C-NanoD
product. The elution order of the C-NanoD species present in the sample follows
approximately their core sizes from small to large. The separated C-NanoD
fractions are collected and characterized by UV absorption spectroscopy,
photoluminescence (PL) spectroscopy, matrix-assisted laser desorption/ionization
time-of-flight mass spectrometry (MALDI-TOF MS), and transmission electron
microscopy (TEM). All the C-NanoD fractions display a distinctive absorption band
at 300 nm, attributing to the n->pi* transition of C=O bond. The PL spectra of
the fractions display emission peaks at 400-415 nm which are slightly red-shifted
with their increase in relative molecular masses. The C-NanoD fractions are fully
anatomized by MALDI-TOF MS, displaying their fragmentation mass ion features. The
core sizes of some selected C-NanoD are determined as 1.6, 1.8, 2.5, and 3.1 nm
by TEM which are in consistent with their HPLC elution order. The findings
highlight the virtues of RP-HPLC to fractionate and reveal the unique
characteristics of individual C-NanoD species present in an as-synthesized C
NanoD product which may have potential applications in the fields of bioanalysis,
bioimaging, catalysis, chemosensing, energy storage, and optoelectronics device.
PMID- 25127630
TI - A fluorescence glucose sensor based on pH induced conformational switch of i
motif DNA.
AB - A facile fluorescence biosensor for the detection of glucose is proposed based on
the pH-induced conformational switch of i-motif DNA in this paper. Glucose can be
oxidized by oxygen (O2) in the presence of glucose oxidase (GOD), and the
generated gluconic acid can decrease the pH value of the solution and then induce
the fluorophore- and quencher-labeled cytosine-rich single-stranded DNA to fold
into a close-packed i-motif structure. As a result, the fluorescence quenching
occurs because of the resonance energy transfer between fluorophore and quencher.
Based on this working principle, the concentration of glucose can be detected by
the decrease of fluorescence density. Under the optimal experimental conditions,
the assay shows a linear response range of 5-100 uM for the glucose concentration
with a detection limit of 4 uM. This glucose biosensor was applied to determine
glucose in real samples successfully, suggesting its potential in the practical
applicability.
PMID- 25127631
TI - Impedimetric detection of alcohol vapours using nanostructured zinc ferrite.
AB - A comparative study on the sensing characteristics of nanostructured zinc ferrite
to three primary alcohols viz. methanol, ethanol and propanol has been carried
out. The zinc ferrite has been prepared by a combustion method and characterized
by XRD, FTIR, AFM and SEM. Impedance studies in the alcohol concentration range
varying from 100 to 1000 ppm show definite variations in response to both the
nature of the alcohol and its concentration. The nanostructured zinc ferrite
shows the highest sensor response to methanol and least to propanol. Equivalent
circuit modelling and calibration have been made for all the three alcohol
sensors. The material shows a better selectivity to the alcohols compared to
formaldehyde, ammonia and acetone vapours.
PMID- 25127632
TI - A new analytical method to determine non-steroidal anti-inflammatory drugs in
surface water using in situ derivatization combined with ultrasound-assisted
emulsification microextraction followed by gas chromatography-mass spectrometry.
AB - Because of the high stability and potential toxic effects of non-steroidal anti
inflammatory drugs (NSAIDs), it is important to closely monitor their
concentrations in the environment using a sensitive analytical method. In this
study, a simple, rapid, efficient, and sensitive analytical method based on gas
chromatography-mass spectrometry (GC-MS) was developed to determine the levels of
seven common NSAIDs in various types of surface water. To simplify sample
preparation, in situ derivatization using methyl chloroformate was combined with
ultrasound-assisted emulsification microextraction. For selection and
optimization of significant variables, experiments were statistically designed
using Plackett-Burman design and central composite design. The resulting optimal
conditions for derivatization and extraction were 100 MUL of chloroform
(extraction solvent), 10.0 mL of sample, and 240 MUL of pyridine (catalyst as a
base in derivatization). The optimized sample preparation coupled with optimized
GC-MS analysis in selected ion monitoring mode provided good linearity from 0.010
to 5.0 ng mL(-1), and a limit of detection between 0.0050 and 0.010 ng mL(-1),
good intra-day and inter-day precision (0.30-6.3% and 5.1-9.5%, respectively),
and good accuracy (relative recovery; 91-117% at 0.20 ng mL(-1) and 77-105% at
2.5 ng mL(-1)). Compared with previously reported methods, the current method
requires a small volume of sample and simple sample preparation steps for
sensitive determination of NSAID levels using a conventional GC-MS system. The
method was successfully applied to determine the levels of seven common NSAIDs in
various types of surface water.
PMID- 25127633
TI - The use of a polymer inclusion membrane as a sorbent for online preconcentration
in the flow injection determination of thiocyanate impurity in ammonium sulfate
fertilizer.
AB - A polymer inclusion membrane (PIM) is used for the first time as a sorbent in the
construction of a preconcentration column to enhance the sensitivity in flow
injection analysis (FIA). The PIM-coated column is readily prepared by coating
the PIM containing poly(vinyl chloride), Aliquat 336, and 1-tetradecanol onto
glass beads packed in a glass tube. The determination of trace amounts of
thiocyanate in ammonium sulfate fertilizer demonstrates the potential of the
proposed PIM-coated column in FIA. Thiocyanate standards or samples of relatively
large volume (e.g. up to 2000 uL) are injected into a nitrate carrier stream. The
sample zone passes through the proposed preconcentration column where thiocyanate
is concentrated in a smaller volume of a carrier solution thus resulting in up to
7.4 fold increase in sensitivity. Thiocyanate is detected spectrophotometrically
after its reaction with Fe(III) downstream of the preconcentration column. The
limits of detection of thiocyanate in the absence and presence of 20 g L(-1)
ammonium sulfate (S/N=2) are 0.014 and 0.024 mg L(-1), respectively. Thiocyanate
was successfully determined in several samples of ammonium sulfate fertilizer.
PMID- 25127634
TI - Facile preparation of octadecyl monoliths with incorporated carbon nanotubes and
neutral monoliths with coated carbon nanotubes stationary phases for HPLC of
small and large molecules by hydrophobic and pi-pi interactions.
AB - Two approaches for incorporating carbon nanotubes into monolithic columns for
HPLC are described in this report. They pertain to the investigation of carbon
nanotubes either (i) as entities to modulate solute retention on monolithic
columns bearing well defined retentive ligands or (ii) as entities that
constitute the stationary phase responsible for solute retention and separation.
Approach (i) involved the incorporation of carbon nanotubes into octadecyl
monolithic columns while approach (ii) concerns the preparation and evaluation of
an ideal monolithic support and coating it with carbon nanotubes to yield a real
"carbon nanotube stationary phase" for the HPLC separation of a wide range of
solutes. First, an octadecyl monolithic column based on the in situ
polymerization of octadecyl acrylate and trimethylolpropane trimethacrylate was
optimized for use in HPLC separations of small and large solutes (e.g.,
proteins). To further modulate the retention and separation of proteins, small
amounts of carbon nanotubes were incorporated into the octadecyl monolith column.
In approach (ii), an inert, relatively polar monolith based on the in situ
polymerization of glyceryl monomethacrylate (GMM) and ethylene glycol
dimethacrylate (EDMA) proved to be the most suitable support for the preparation
of "carbon nanotube stationary phase". This carbon nanotube "coated" monolith
proved useful in the HPLC separation of a wide range of small solutes including
enantiomers. In approach (ii), a more homogeneous incorporation of carbon
nanotubes into the diol monolithic columns (i.e., GMM/EDMA) was achieved when
hydroxyl functionalized carbon nanotubes were incorporated into the GMM/EDMA
monolithic support. In addition, high power sonication for a short time enhanced
further the homogeneity of the monolith incorporated with nanotubes. In all
cases, nonpolar and pi interactions were responsible for solute retention on the
monolith incorporated carbon nanotubes.
PMID- 25127635
TI - Low gas flow inductively coupled plasma optical emission spectrometry for the
analysis of food samples after microwave digestion.
AB - In this work, the recently introduced low flow inductively coupled plasma optical
emission spectrometry (ICP-OES) with a total argon consumption below 0.7 L/min is
applied for the first time to the field of food analysis. One goal is the
investigation of the performance of this low flow plasma compared to a
conventional ICP-OES system when non-aqueous samples with a certain matrix are
introduced into the system. For this purpose, arsenic is determined in three
different kinds of fish samples. In addition several nutrients (K, Na, Mg, Ca)
and trace metals (Co, Cu, Mn, Cd, Pb, Zn, Fe, and Ni) are determined in honey
samples (acacia) after microwave digestion. The precision of the measurements is
characterized by relative standard deviations (RSD) and compared to the
corresponding precision values achieved using the conventional Fassel-type torch
of the ICP. To prove the accuracy of the low flow ICP-OES method, the obtained
data from honey samples are validated by a conventional ICP-OES. For the
measurements concerning arsenic in fish, the low flow ICP-OES values are
validated by conventional Fassel-type ICP-OES. Furthermore, a certified reference
material was investigated with the low gas flow setup. Limits of detection (LOD),
according to the 3sigma criterion, were determined to be in the low microgram per
liter range for all analytes. Recovery rates in the range of 96-106% were
observed for the determined trace metal elements. It was proven that the low gas
flow ICP-OES leads to results that are comparable with those obtained with the
Fassel-type torch for the analysis of food samples.
PMID- 25127636
TI - New method for the determination of carbamate and pyrethroid insecticides in
water samples using on-line SPE fused core column chromatography.
AB - A new HPLC column-switching method using large volume sample injection and fused
core columns for on-line solid phase extraction have been developed for the
determination of the following carbamates and pyrethroids: aldicarb, carbaryl,
pirimicarb, carbofuran, kadethrin, flumethrin, fenpropathrin, fenoxycarb, tau
fluvalinate and fenvalerate, in surface water samples. Sudan I was used as
internal standard. The proposed method was performed using 100 ul sample
injection followed by an on-line solid phase extraction procedure and finally the
compounds were identified and quantified by liquid chromatography with
ultraviolet detection. The separation was carried out on C-18 reversed phase
column based on fused-core particle technology. The influence of the injected
sample volume, the variables affecting to SPE process and the conditions for the
separation on an analytical column, were studied and optimized. The limits of
detection ranged from 5.5 to 8.9 ug L(-1), and limits of quantification from 18.4
to 29.7 ug L(-1), while inter- and intra-day variability was under 15%. This new
analytical procedure was satisfactorily applied for the determination of these
organic pollutants in surface water samples located in Czech Republic.
Concentration levels were found for some of these pollutants up to 26.11 ug L(-1)
in the river Elbe and up to 34.53 ug L(-1) in the closed lakes samples.
PMID- 25127637
TI - Thermogravimetric study of vapor pressure of TATP synthesized without
recrystallization.
AB - This study aims at characterizing the vapor pressure signatures generated by
triacetone triperoxide (TATP) that was synthesized without recrystallization by
thermogravimmetric analysis (TGA) for exploitation by standoff detection
technologies of explosive devices. The thermal behavior of the nonrecrystallized
sample was compared with reported values. Any phase change, melting point and
decomposition identification were studied by differential scanning calorimeter.
Vapor pressures were estimated by the Langmuir method of evaporation from an open
surface in a vacuum. Vapor pressures of TATP at different temperatures were
calculated using the linear logarithmic relationship obtained from benzoic acid
reference standard. Sublimation of TATP was found to follow apparent zero-order
kinetics and sublimes at steady rates at 298 K and above. While the enthalpy of
sublimation found, 71.7 kJ mol(-1), is in agreement with reported values the
vapor pressures deviated significantly. The differences in the vapor pressures
behavior are attributable to the synthesis pathway chosen in this study.
PMID- 25127638
TI - Electrochemical immunosensor for the analysis of the breast cancer biomarker HER2
ECD.
AB - Human epidermal growth factor receptor 2 (HER2) is a breast cancer biomarker that
plays a major role in promoting breast cancer cell proliferation and malignant
growth. The extracellular domain (ECD) of HER2 can be shed into the blood stream
and its concentration is measurable in the serum fraction of blood. In this work
an electrochemical immunosensor for the analysis of HER2 ECD in human serum
samples was developed. To achieve this goal a screen-printed carbon electrode,
modified with gold nanoparticles, was used as transducer surface. A sandwich
immunoassay, using two monoclonal antibodies, was employed and the detection of
the antibody-antigen interaction was performed through the analysis of an
enzymatic reaction product by linear sweep voltammetry. Using the optimized
experimental conditions the calibration curve (ip vs. log[HER2 ECD]) was
established between 15 and 100 ng/mL and a limit of detection (LOD) of 4.4 ng/mL
was achieved. These results indicate that the developed immunosensor could be a
promising tool in breast cancer diagnostics, patient follow-up and monitoring of
metastatic breast cancer since it allows quantification in a useful concentration
range and has an LOD below the established cut-off value (15 ng/mL).
PMID- 25127639
TI - Polydimethylsiloxane/metal-organic frameworks coated fiber for solid-phase
microextraction of polycyclic aromatic hydrocarbons in river and lake water
samples.
AB - In this study, polydimethylsiloxane/metal-organic frameworks (PDMS/MOFs),
including PDMS/MIL-101 and PDMS/MOF-199, were immobilized onto a stainless steel
wire through sol-gel technique as solid-phase microextraction (SPME) fiber
coating. The prepared fibers were used for the extraction of some polycyclic
aromatic hydrocarbons (PAHs) from water samples prior to gas chromatography-mass
spectrometry (GC-MS) analysis. Under the optimized experiment conditions, the
PDMS/MIL-101 coated fiber exhibited higher extraction efficiency towards PAHs
than that of PDMS/MOF-199. Several parameters affecting the extraction of PAHs by
SPME with PDMS/MIL-101 fiber, including the extraction temperature, extraction
time, sample volume, salt addition and desorption conditions, were investigated.
The limits of detection (LODs) were less than 4.0 ng L(-1) and the linearity was
observed in the range from 0.01 to 2.0 ug L(-1) with the correlation coefficients
(r) ranging from 0.9940 to 0.9986. The recoveries of the method for the PAHs from
water samples at spiking levels of 0.05 and 0.2 ug L(-1) ranged from 78.2% to
110.3%. Single fiber repeatability and fiber-to-fiber reproducibility were less
than 9.3% and 13.8%, respectively.
PMID- 25127640
TI - Over a century of detection and quantification capabilities in analytical
chemistry--historical overview and trends.
AB - The detection limit (LD) and the quantification limit (LQ) are important
parameters in the validation process. Estimation of these parameters is
especially important when trace and ultra-trace quantities of analyte are to be
detected. When the apparatus response from the analyte is below the detection
limit, it does not necessarily mean that the analyte is not present in the
sample. It may be a message that the analyte concentration could be below the
detection capabilities of the instrument or analytical method. By using a more
sensitive detector or a different analytical method it is possible to
quantitatively determine the analyte in a given sample. The terms associated with
detection capabilities have been present in the scientific literature for at
least the past 100 years. Numerous terms, definitions and approaches to
calculations have been presented during that time period. This paper is an
attempt to collect and summarize the principal approaches to the definition and
calculation of detection and quantification abilities published from the
beginning of 20th century up until the present. Some of the most important
methods are described in detail. Furthermore, the authors would like to
popularize the knowledge of metrology in chemistry, particularly that part of it
which concerns validation of the analytical procedure.
PMID- 25127641
TI - A portable DNAzyme-based optical biosensor for highly sensitive and selective
detection of lead (II) in water sample.
AB - A portable, rapid and cost-effective DNAzyme based sensor for lead ions detection
in water samples has been developed using an optical fiber sensor platform. The
presence of Pb(2+) cleaves the DNAzymes and releases the fluorescent labeled
fragments, which further hybridize with the complementary strands immobilized on
the optic fiber sensor surface. Subsequent fluorescent signals of the hybridized
fluorescent labeled fragment provides quantitative information on the
concentrations of Pb(2+) with a dynamic range from 2-75 nM with a detection limit
of 1.03 nM (0.21 ng mL(-1)). The proposed sensor also shows good selectivity
against other mono and divalent metal ions and thus holds great potential for the
construction of general DNAzyme-based sensing platform for the monitoring of
other heavy metal ions. The sensor can be regenerated with a 1% SDS solution (pH
1.9) over 100 times without significant deterioration of the sensor performance.
This portable sensor system can be potentially applied for on-site real-time
inexpensive and easy-to-use monitoring of Pb(2+) in environmental samples such as
wastewater effluents or water bodies.
PMID- 25127642
TI - Development and characterisation of a new Sr selective resin for the rapid
determination of 90Sr in environmental water samples.
AB - A new resin selective for Sr has been developed and characterised for the direct
binding of (90)Sr from environmental waters with minimal pre-treatment. The new
selective resin comprises of a mixture of two extractants, 4,4'(5')-bis-t
butylcyclohexano-18-crown-6 and di(2-ethyl-hexyl)phosphoric acid, sorbed onto
Amberchrom CG-71. Sr uptake is shown to be high (the distribution weight
coefficient Dw >100 mL g(-1)) across a range of environmentally realistic
conditions (pH 2-8 and up to 11,500 mg L(-1) NaCl, 500 mg L(-1) Ca, 400 mg L(-1)
K and 1300 mg L(-1) Mg). The Sr capacity of the resin is shown to be 7.7+/-0.4 mg
g(-1), meaning that the resin has a sufficient capacity to quantitatively remove
Sr from most environmental water samples. The reasonably fast uptake kinetics of
the resin (95+/-4% of strontium bound within 30 min) results in a resin that is
applicable to both batch- and column-type separation procedures. A range of
potentially co-extracted radio-elements have been identified and an elution
scheme has been developed to separate interferences, including (90)Y, from
(90)Sr. The clean elution of (90)Sr permits immediate measurement by radiometric
means, with no need for complicated spectral processing or waiting for secular
equilibrium between (90)Sr and (90)Y. The characterised resin is applicable for
use in rapid determination procedures, enabling the swift analysis of water
samples required by monitoring schemes at contaminated nuclear sites and in the
aftermath of nuclear accidents.
PMID- 25127643
TI - Characterization of volatile components in four vegetable oils by headspace two
dimensional comprehensive chromatography time-of-flight mass spectrometry.
AB - Edible oil adulteration is the biggest source of food fraud all over the world.
Since characteristic aroma is an important quality criterion for edible oils, we
analyzed volatile organic compounds (VOCs) in four edible vegetable oils
(soybean, peanut, rapeseed, and sunflower seed oils) by headspace comprehensive
two-dimensional gas chromatography time-of-flight mass spectrometry (Headspace
GC*GC-TOFMS) in this study. After qualitative and quantitative analysis of VOCs,
we used unsupervised (PCA) and supervised (Random forests) multivariate
statistical methods to build a classification model for the four edible oils. The
results indicated that the four edible oils had their own characteristic VOCs,
which could be used as markers to completely classify these four edible oils into
four groups.
PMID- 25127645
TI - Assessing oral bioaccessibility of trace elements in soils under worst-case
scenarios by automated in-line dynamic extraction as a front end to inductively
coupled plasma atomic emission spectrometry.
AB - A novel biomimetic extraction procedure that allows for the in-line handing of
>=400 mg solid substrates is herein proposed for automatic ascertainment of trace
element (TE) bioaccessibility in soils under worst-case conditions as per
recommendations of ISO norms. A unified bioaccessibility/BARGE method (UBM)-like
physiological-based extraction test is evaluated for the first time in a dynamic
format for accurate assessment of in-vitro bioaccessibility of Cr, Cu, Ni, Pb and
Zn in forest and residential-garden soils by on-line coupling of a hybrid flow
set-up to inductively coupled plasma atomic emission spectrometry. Three
biologically relevant operational extraction modes mimicking: (i) gastric juice
extraction alone; (ii) saliva and gastric juice composite in unidirectional flow
extraction format and (iii) saliva and gastric juice composite in a recirculation
mode were thoroughly investigated. The extraction profiles of the three
configurations using digestive fluids were proven to fit a first order reaction
kinetic model for estimating the maximum TE bioaccessibility, that is, the actual
worst-case scenario in human risk assessment protocols. A full factorial design,
in which the sample amount (400-800 mg), the extractant flow rate (0.5-1.5 mL
min(-1)) and the extraction temperature (27-37 degrees C) were selected as
variables for the multivariate optimization studies in order to obtain the
maximum TE extractability. Two soils of varied physicochemical properties were
analysed and no significant differences were found at the 0.05 significance level
between the summation of leached concentrations of TE in gastric juice plus the
residual fraction and the total concentration of the overall assayed metals
determined by microwave digestion. These results showed the reliability and lack
of bias (trueness) of the automatic biomimetic extraction approach using
digestive juices.
PMID- 25127646
TI - Chemometric processing of second-order liquid chromatographic data with UV-vis
and fluorescence detection. A comparison of multivariate curve resolution and
parallel factor analysis 2.
AB - Second-order liquid chromatographic data with multivariate spectral (UV-vis or
fluorescence) detection usually show changes in elution time profiles from sample
to sample, causing a loss of trilinearity in the data. In order to analyze them
with an appropriate model, the latter should permit a given component to have
different time profiles in different samples. Two popular models in this regard
are multivariate curve resolution-alternating least-squares (MCR-ALS) and
parallel factor analysis 2 (PARAFAC2). The conditions to be fulfilled for
successful application of the latter model are discussed on the basis of simple
chromatographic concepts. An exhaustive analysis of the multivariate calibration
models is carried out, employing both simulated and experimental chromatographic
data sets. The latter involve the quantitation of benzimidazolic and carbamate
pesticides in fruit and juice samples using liquid chromatography with diode
array detection, and of polycyclic aromatic hydrocarbons in water samples, in
both cases in the presence of potential interferents using liquid chromatography
with fluorescence spectral detection, thereby achieving the second-order
advantage. The overall results seem to favor MCR-ALS over PARAFAC2, especially in
the presence of potential interferents.
PMID- 25127647
TI - Electrochemical monitoring of intracellular enzyme activity of single living
mammalian cells by using a double-mediator system.
AB - We evaluated the intracellular NAD(P)H: quinone oxidoreductase (NQO) activity of
single HeLa cells by using the menadione-ferrocyanide double-mediator system
combined with scanning electrochemical microscopy (SECM). The double-mediator
system was used to amplify the current response from the intracellular NQO
activity and to reduce menadione-induced cell damage. The electron shuttle
between the electrode and menadione was mediated by the ferrocyanide/ferricyanide
redox couple. Generation of ferrocyanide was observed immediately after the
addition of a lower concentration (10 MUM) of menadione. The ferrocyanide
generation rate was constant for 120 min. At a higher menadione concentration
(100 MUM), the ferrocyanide generation rate decreased within 30 min because of
the cytotoxic effect of menadione. We also investigated the relationship between
intracellular reactive oxygen species or glutathione levels and exposure to
different menadione concentrations to determine the optimal condition for SECM
with minimal invasiveness. The present study clearly demonstrates that SECM is
useful for the analysis of intracellular enzymatic activities in single cells
with a double-mediator system.
PMID- 25127648
TI - Application of the diffusive gradients in thin films technique for available
potassium measurement in agricultural soils: effects of competing cations on
potassium uptake by the resin gel.
AB - The utilization of Amberlite (IRP-69 ion-exchange resin, 100-500 wet mesh) as the
binding phase in the diffusive gradients in thin films (DGT) technique has shown
potential to improve the assessment of plant-available K in soils. The binding
phase has recently been optimized by using a mixed Amberlite and ferrihydrite
(MAF) gel which results in linear K uptake over extended deployment periods and
in solutions with higher K concentrations. As restriction of K uptake by Ca on
the Amberlite based resin gel has been previously proposed, potential competing
effects of Ca(2+), Mg(2+) and NH(4+) on K uptake by the MAF gel were
investigated. These cations had no effect on K elution efficiency which was 85%.
However, K uptake by the MAF gel was restricted in the presence of competing
cations in solution. Consequently, the diffusion coefficient of K decreased in
the presence of cations compared to previous studies but was stable at 1.12*10(
5)cm(2)s(-1) at 25 degrees C regardless of cation concentrations. Uptake of K by
the DGT device was affected by the presence of excessive Ca in more than 30% of
twenty typical Australian agricultural soils. However, this problem could be
circumvented by using a shorter deployment time than the normal 24 h. Moderate
correlation of concentrations of K extracted by DGT with Colwell K (extracted by
NaHCO(3), R(2)=0.69) and NH4OAc K (R(2)=0.61) indicates that DGT measures a
different pool of K in soils than that measured by the standard extractants used.
In addition, the MAF gel has the ability to measure Ca and Mg simultaneously.
PMID- 25127644
TI - Associations of sleep disturbance with ADHD: implications for treatment.
AB - Attention-deficit/hyperactivity disorder (ADHD) is commonly associated with
disordered or disturbed sleep. The relationships of ADHD with sleep problems,
psychiatric comorbidities and medications are complex and multidirectional.
Evidence from published studies comparing sleep in individuals with ADHD with
typically developing controls is most concordant for associations of ADHD with:
hypopnea/apnea and peripheral limb movements in sleep or nocturnal motricity in
polysomnographic studies; increased sleep onset latency and shorter sleep time in
actigraphic studies; and bedtime resistance, difficulty with morning awakenings,
sleep onset difficulties, sleep-disordered breathing, night awakenings and
daytime sleepiness in subjective studies. ADHD is also frequently coincident with
sleep disorders (obstructive sleep apnea, peripheral limb movement disorder,
restless legs syndrome and circadian-rhythm sleep disorders). Psychostimulant
medications are associated with disrupted or disturbed sleep, but also
'paradoxically' calm some patients with ADHD for sleep by alleviating their
symptoms. Long-acting formulations may have insufficient duration of action,
leading to symptom rebound at bedtime. Current guidelines recommend assessment of
sleep disturbance during evaluation of ADHD, and before initiation of
pharmacotherapy, with healthy sleep practices the first-line option for
addressing sleep problems. This review aims to provide a comprehensive overview
of the relationships between ADHD and sleep, and presents a conceptual model of
the modes of interaction: ADHD may cause sleep problems as an intrinsic feature
of the disorder; sleep problems may cause or mimic ADHD; ADHD and sleep problems
may interact, with reciprocal causation and possible involvement of comorbidity;
and ADHD and sleep problems may share a common underlying neurological etiology.
PMID- 25127649
TI - The importance of chain length for the polyphosphate enhancement of acidic
potassium permanganate chemiluminescence.
AB - Sodium polyphosphate is commonly used to enhance chemiluminescence reactions with
acidic potassium permanganate through a dual enhancement mechanism, but
commercially available polyphosphates vary greatly in composition. We have
examined the influence of polyphosphate composition and concentration on both the
dual enhancement mechanism of chemiluminescence intensity and the stability of
the reagent under analytically useful conditions. The average chain length (n)
provides a convenient characterisation, but materials with similar values can
exhibit markedly different distributions of phosphate oligomers. There is a
minimum polyphosphate chain length (~6) required for a large enhancement of the
emission intensity, but no further advantage was obtained using polyphosphate
materials with much longer average chain lengths. Providing there is a sufficient
average chain length, the optimum concentration of polyphosphate is dependent on
the analyte and in some cases, may be lower than the quantities previously used
in routine detection. However, the concentration of polyphosphate should not be
lowered in permanganate reagents that have been partially reduced to form high
concentrations of the key manganese(III) co-reactant, as this intermediate needs
to be stabilised to prevent formation of insoluble manganese(IV).
PMID- 25127650
TI - Absolute quantification of superoxide dismutase in cytosol and mitochondria of
mice hepatic cells exposed to mercury by a novel metallomic approach.
AB - In the last years, the development of new methods for analyzing accurate and
precise individual metalloproteins is of increasing importance, since numerous
metalloproteins are excellent biomarkers of oxidative stress and diseases. In
that way, methods based on the use of post column isotopic dilution analysis
(IDA) or enriched protein standards are required to obtain a sufficient degree of
accuracy, precision and high limits of detection. This paper reports the
identification and absolute quantification of Cu,Zn-superoxide dismutase (Cu,Zn
SOD) in cytosol and mitochondria from mice hepatic cells using a innovative
column switching analytical approach. The method consisted of orthogonal
chromatographic systems coupled to inductively coupling plasma-mass spectrometry
equipped with a octopole reaction systems (ICP-ORS-MS) and UV detectors: size
exclusion fractionation (SEC) of the cytosolic and mitochondrial extracts
followed by online anion exchange chromatographic (AEC) separation of Cu/Zn
containing species. After purification, Cu,Zn-SOD was identified after tryptic
digestion by molecular mass spectrometry (MS). The MS/MS spectrum of a doubly
charged peptide was used to obtain the sequence of the protein using the MASCOT
searching engine. This optimized methodology reduces the time of analysis and
avoids the use of sample preconcentration and clean-up procedures, such as cut
off centrifuged filters, solid phase extraction (SPE), precipitation procedures,
off-line fractions insolates, etc. In this sense, the method is robust, reliable
and fast with typical chromatographic run time less than 20 min. Precision in
terms of relative standard deviation (n = 5) is of 3-5% and detection limits is
0.21 ngCug(-1). The application of the methodology to hepatic cells from mice
exposed to inorganic mercury reveals decreased levels of Cu,Zn-SOD in cytosolic
and mitochondrial extracts, as a consequence of the oxidative stress caused by
this toxic metal. Additionally, the quantification of mitochondrial Cu,Zn-SOD in
hepatic cells from Mus musculus has been carried out for the first time.
PMID- 25127651
TI - In-situ vibrational optical rotatory dispersion of molecular organic crystals at
high pressures.
AB - Organic structures respond to pressure with a variety of mechanisms including
degradation, intramolecular transformation and intermolecular bonding. The
effects of pressure on chiral organic structures are of particular interest
because of the potential steric controls on the fate of pressurized molecules.
Despite representing a range of opportunities, the simultaneous study of high
pressures on different forms of chiral structures is poorly explored. We have
combined synchrotron-source vibrational optical rotatory dispersion, micro
Fourier transform infrared spectroscopy and the use of a diamond anvil cell to
simultaneously monitor the effects of pressure on the two enantiomers of the
simple amino acid, alanine.
PMID- 25127652
TI - Highly selective silver nanoparticles based label free colorimetric sensor for
nitrite anions.
AB - Highly selective label free colorimetric sensor based on AgNPs stabilized by
phenolic chelating ligand, N,N'-bis(2-hydroxybenzyl)-1,2-diaminobenzene (1), for
NO(2-) anions has been developed. Addition of NO(2-) showed selective
decolourisation of brownish yellow colour of 1-AgNPs with the detection limit of
10(-7)M. Absorption studies showed the complete disappearance of 1-AgNPs peak at
426 nm due to the conversion of AgNPs to silver ions. The presence silver ions
were confirmed by white precipitates of AgCl formation with NaCl. The
interference studies confirmed the high selectivity of NO(2-) sensing in presence
of anions as well as cations by 1-AgNPs. A linear relationship was observed
between the change of absorption and concentration of NO(2-). The present
approach could be performed at room temperature and ambient conditions. The
practical applications of 1-AgNPs for selective sensing of NO(2-) in different
water samples such as ground, river, pond and tap water have also been
demonstrated.
PMID- 25127653
TI - Magnetically assisted solid phase extraction using Fe3O4 nanoparticles combined
with enhanced spectrofluorimetric detection for aflatoxin M1 determination in
milk samples.
AB - A novel, facile and inexpensive solid phase extraction (SPE) method using
ethylene glycol bis-mercaptoacetate modified 3-(trimethoxysilyl)-1-propanethiol
grafted Fe(3)O(4) nanoparticles coupled with spectrofluorimetric detection was
proposed for determination of aflatoxin M1 (AFM1) in liquid milk samples. The
method uses the advantage fluorescence enhancement by beta-cyclodexterin
complexation of AFM1 in 12% (v/v) acetonitrile-water and the remarkable
properties of Fe(3)O(4) nanoparticles namely high surface area and strong
magnetization were utilized to achieve high enrichment factor (57) and
satisfactory extraction recoveries (91-102%) using only 100 mg of magnetic
adsorbent. Furthermore, fast separation time of about 15 min avoids many time
consuming column-passing procedures of conventional SPE. The main factors
affecting extraction efficiency including pH value, desorption conditions,
extraction/desorption time, sample volume, and adsorbent amount were evaluated
and optimized. Under the optimal conditions, a wide linear range of 0.04-8 ng mL(
1) with a low detection limit of 0.015 ng mL(-1) was obtained. The developed
method was applied for extraction and preconcentration of AFM1 in three
commercially available milk samples and the results were compared with the
official AOAC method.
PMID- 25127654
TI - Text recycling: acceptable or misconduct?
AB - Text recycling, also referred to as self-plagiarism, is the reproduction of an
author's own text from a previous publication in a new publication. Opinions on
the acceptability of this practice vary, with some viewing it as acceptable and
efficient, and others as misleading and unacceptable. In light of the lack of
consensus, journal editors often have difficulty deciding how to act upon the
discovery of text recycling. In response to these difficulties, we have created a
set of guidelines for journal editors on how to deal with text recycling. In this
editorial, we discuss some of the challenges of developing these guidelines, and
how authors can avoid undisclosed text recycling.
PMID- 25127655
TI - Reduced-dose warfarin or interrupted warfarin with heparin bridging for pacemaker
or defibrillator implantation: a randomized trial.
AB - BACKGROUND: Perioperative management with reduced-dose warfarin is of potential
interest by eliminating the need for bridging while still maintaining a degree of
anticoagulation. The outcomes of this regimen have not been well determined.
METHODS: In a randomized controlled trial we compared two regimens for management
of anticoagulation with warfarin in patients with implantation of a pacemaker or
defibrillator. Half dose of warfarin for 3-6 days, depending on the baseline
international normalized ratio (INR), before surgery aiming at an INR of <= 1.7
was compared with interrupted warfarin for 5 days with preoperative bridging with
low-molecular-weight heparin (LMWH) at therapeutic dose for 2.5 days. Main safety
outcome was pocket hematoma. Secondary outcomes were major bleeding,
thromboembolism - all within 1 month, days of hospitalization and number of
patients requiring correction of INR with vitamin K. RESULTS: The study was
planned for 450 patients but it was discontinued prematurely due to a change in
practice. Pocket hematoma occurred in 4 of 85 patients (5%) randomized to the
bridged regimen and in 3 of 86 patients (3%) randomized to reduced-dose warfarin.
One pocket hematoma in each group was severe. There were no major hemorrhages or
thromboembolism within the 1-month window. Duration of hospitalization was
similar in the two groups. Correction of INR the day before surgery with vitamin
K had to be used for significantly more patients in the reduced-dose warfarin
group (41%) than in the bridged regimen group (6%). CONCLUSION: The reduced-dose
warfarin regimen appeared to have similar safety after device implantation as
interrupted warfarin with preoperative LMWH bridging. Due to premature
discontinuation no firm conclusion can be drawn. The reduced-dose warfarin
regimen often failed to achieve the intended preoperative INR. ClinicalTrials.gov
Identifier: NCT 02094157.
PMID- 25127656
TI - Pharmacokinetics of vancomycin in critically ill patients undergoing continuous
venovenous haemodialysis.
PMID- 25127658
TI - The geostatistic-based spatial distribution variations of soil salts under long
term wastewater irrigation.
AB - The purpose of this study was to determine and evaluate the spatial changes in
soil salinity by using geostatistical methods. The study focused on the suburb
area of Beijing, where urban development led to water shortage and accelerated
wastewater reuse to farm irrigation for more than 30 years. The data were then
processed by GIS using three different interpolation techniques of ordinary
kriging (OK), disjunctive kriging (DK), and universal kriging (UK). The normality
test and overall trend analysis were applied for each interpolation technique to
select the best fitted model for soil parameters. Results showed that OK was
suitable for soil sodium adsorption ratio (SAR) and Na(+) interpolation; UK was
suitable for soil Cl(-) and pH; DK was suitable for soil Ca(2+). The nugget-to
sill ratio was applied to evaluate the effects of structural and stochastic
factors. The maps showed that the areas of non-saline soil and slight salinity
soil accounted for 6.39 and 93.61%, respectively. The spatial distribution and
accumulation of soil salt were significantly affected by the irrigation
probabilities and drainage situation under long-term wastewater irrigation.
PMID- 25127659
TI - Palonosetron versus ondansetron as rescue medication for postoperative nausea and
vomiting: a randomized, multicenter, open-label study.
AB - BACKGROUND: This study compared palonosetron and ondansetron as rescue
medications for postoperative nausea and vomiting (PONV) in patients who received
prophylactic ondansetron. Although guidelines recommend use of an agent from a
different class when prophylaxis has failed, palonosetron has unique properties
relative to other serotonin 5-HT3 receptor antagonists. Prior trials assessing
its use for rescue have had conflicting results. Although palonosetron has
compared favorably with ondansetron for PONV prevention, the drugs have not been
compared in the rescue setting of failure of 5-HT3 receptor antagonist
prophylaxis. METHODS: This was a randomized, open-label, multicenter trial
comparing the efficacy and safety of intravenous palonosetron 0.075 mg and
intravenous ondansetron 4 mg in patients experiencing PONV following laparoscopic
abdominal or gynecological surgery despite prophylactic ondansetron. RESULTS: Of
239 patients screened, 220 were enrolled and 98 were treated for PONV: 48 and 50
in the palonosetron and ondansetron arms, respectively. Complete control during
72 hours after study drug administration was achieved in 25.0% of palonosetron
recipients and 18.0% of ondansetron recipients (95% confidence interval [CI],
9.2, 23.3; p = 0.40). Corresponding incidences of vomiting were 29.2% for
palonosetron and 48.0% for ondansetron (95% CI, -0.06, 37.7; p = 0.057), and
62.5% and 56.0% required additional rescue treatment, respectively (95% CI,
25.9, 12.9; p = 0.52). Other than a similar incidence of procedural pain in the 2
groups, the most common treatment-emergent adverse events, which were generally
mild, were headache (14.6% vs 12.0%), constipation (8.3% vs 10.0%), and dizziness
(6.3% vs 8.0%), for the palonosetron and ondansetron groups, respectively.
CONCLUSIONS: Palonosetron and ondansetron did not show differences in the primary
efficacy endpoint of CC during the 72 hours after study drug administration.
There was a trend toward less emesis in the 0-72 h time period favoring
palonosetron. While larger studies are needed to fully assess any clinical
benefits of palonosetron to rescue patients who have failed ondansetron
prophylaxis for PONV, the benefit, if any, would be limited based on this study.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT00967499 (Registered August 27, 2009).
PMID- 25127657
TI - Novel self assembling nanoparticles for the oral administration of fondaparinux:
synthesis, characterization and in vivo evaluation.
AB - Fondaparinux (Fpx) is the anticoagulant of choice in the treatment of short- and
medium-term thromboembolic disease. To overcome the low oral bioavailability of
Fpx, a new nanoparticulate carrier has been developed. The nanoparticles (NPs)
contain squalenyl derivatives, known for their excellent oral bioavailability.
They spontaneously self-assemble upon both electrostatic and hydrophobic
interactions between the polyanionic Fpx and cationic squalenyl (CSq)
derivatives. The preparation conditions were optimized to obtain monodisperse,
stable NPs with a mean diameter in the range of 150-200 nm. The encapsulation
efficiencies were around 80%. Fpx loadings reached 39 wt.%. According to
structural and morphological analysis, Fpx and CSq organized in spherical
multilamellar ("onion-type") nanoparticles. Furthermore, in vivo studies in rats
suggested that Fpx was well absorbed from the orally administered NPs, which
totally dissociated when reaching the blood stream, leading to the release of
free Fpx. The Fpx:CSq NPs improved the plasmatic concentration of Fpx in a dose
dependent manner. However, the oral bioavailability of these new NPs remained low
(around 0.3%) but of note, the Cmax obtained after oral administration of 50mg/kg
NPs was close to the prophylactic plasma concentration needed to treat venous
thromboembolism. Moreover, the oral bioavailability of Fpx could be dramatically
increased up to 9% by including the nanoparticles into gastroresistant capsules.
This study opens up new perspectives for the oral administration of Fpx and paves
the way towards elaborating squalene-based NPs which self assemble without the
need of covalently grafting the drug to Sq.
PMID- 25127660
TI - Plasmalogens in the retina: from occurrence in retinal cell membranes to
potential involvement in pathophysiology of retinal diseases.
AB - Plasmalogens (Pls) represent a specific subclass of glycerophospholipids
characterized by the presence of a vinyl-ether bond at the sn-1 position of
glycerol. Pls are quantitatively important in membranes of neuronal tissues,
including the brain and the retina, where they can represent until almost two
third of ethanolamine glycerophospholipids. They are considered as reservoirs of
polyunsaturated fatty acids as several studies have shown that arachidonic and
docosahexaenoic acids are preferentially esterified on Pls when compared to other
glycerophospholipids. Reduced levels of Pls were observed in a number of
neurodegenerative disorders such as glaucoma, the second leading cause of
blindness worldwide. In a mouse model of Pls deficiency, "glaucoma-like" optic
nerve abnormalities were observed as well as developmental defects in the eye.
These included microphthalmia, dysgenesis of the anterior segment of the eye, and
abnormalities in retinal vessel architecture. Several data from animal and in
vitro studies suggest that Pls may be involved in the regulation of retinal
vascular development through the release of polyunsaturated fatty acids by a
calcium-independent phospholipase A2.
PMID- 25127661
TI - Critical roles of DNase1l3l in lens nuclear degeneration in zebrafish.
AB - The vertebrate lens undergoes organelle and nuclear degradation during lens
development, allowing the lens to become transparent. DNase2b is an enzyme
responsible for nuclear degradation in the mouse lens; however, dnase2b
expression in zebrafish showed a distribution pattern that differed from that in
mice. No zebrafish dnase2b was detected by reverse-transcription polymerase chain
reaction until around 120 h postfertilization (hpf), suggesting that dnase2b is
not expressed in the critical period for lens nuclear degradation, which
corresponds to 56-74 hpf. However, public database searches have indicated that
dnase1l3l is strongly and specifically expressed in embryonic zebrafish lens.
Whole mount in situ hybridization showed that dnase1l3l expression began around
36 hpf and was found exclusively in the lens until the adult stage. Morpholino
(MO)-dependent downregulation of dnase1l3l expression during early development in
zebrafish led to the failure of nuclear degradation in the lens. Immunostaining
of lens sections showed that expression of Pax6, Prox1 and beta-catenin was
comparable to the control in the early stage of development in dnase1l3l-MO
injected embryos. However, downregulation of expression of these genes in lens
was not observed in dnase1l3l-MO-treated zebrafish at 72 hpf, suggesting that the
lens development was halted. Taken together, we showed that dnase1l3l plays major
roles in nuclear degradation in zebrafish lens development. No homologous gene
was found in other species in public databases, suggesting that dnase1l3l
developed and acquired its function specifically in zebrafish.
PMID- 25127662
TI - Women's participation in breast cancer screening in France--an ethical approach.
AB - BACKGROUND: Breast cancer is a major public health challenge. Organized
mammography screening (OS) is considered one way to reduce breast cancer
mortality. EU recommendations prone mass deployment of OS, and back in 2004,
France introduced a national OS programme for women aged 50-74 years. However, in
2012, participation rate was still just 52.7%, well short of the targeted 70%
objective. In an effort to re-address the (in) efficiency of the programme, the
French National Cancer Institute has drafted an expert-group review of the
ethical issues surrounding breast cancer mammography screening. DISCUSSION:
Prompted by emerging debate over the efficiency of the screening scheme and its
allied public information provision, we keynote the experts' report based on
analysis of epidemiological data and participation rate from the public health
authorities. The low coverage of the OS scheme may be partly explained by the
fact that a significant number of women undergo mammography outside OS and thus
outside OS criteria. These findings call for further thinking on (i) the ethical
principles of beneficence and non-malfeasance underpinning this public health
initiative, (ii) the reasons behind women's and professionals' behavior, and
(iii) the need to analyze how information provision to women and the doctor
patient relationship need to evolve in response to scientific controversy over
the risks and benefits of conducting mammographic screening. SUMMARY: This work
calls for a reappraisal of the provision of screening programme information. We
advocate a move to integrate the points sparking debate over the efficiency of
the screening scheme to guarantee full transparency. The perspective is to
strengthen the respect for autonomy allowing women to make an informed choice in
their decision on whether or not to participate.
PMID- 25127664
TI - Estimating prevalence and burden of major disorders of the brain in Nepal:
cultural, geographic, logistic and philosophical issues of methodology.
AB - BACKGROUND: Headache, anxiety and depression are major disorders of the brain in
terms of their prevalence and the burdens and costs they impose on society.
Nationwide population-based studies of these disorders are necessary to inform
health policy but, in research-naive and resource-poor countries such as Nepal, a
host of methodological problems are encountered: cultural, geographic, logistic
and philosophical. METHODS: Expert consensus was sought among researchers from
different professional and cultural backgrounds in planning and conceptualizing
an epidemiological study and adapting established methods to the special
situation and circumstances of Nepal. RESULTS: The methodological problems were
sorted into different themes: study design; climate; geography, access and
transport; sociocultural issues; safety of interviewers. Each of these was dealt
with separately, and their inter-relationships explored, in finding solutions
that were sometimes pragmatic. A cross-sectional questionnaire-based study, with
teams of interviewers visiting households across the three physiographic
divisions (with extremes in altitude) in each of the five development regions of
the country, would enable national sampling with sociocultural
representativeness. However, the study instruments and interviews would be in
Nepali only. Transport and access challenges were considerable, and their
solutions combined travel by air, bus, river and foot, with allowances for rain
damaged roads, collapsed bridges and cancelled scheduled flights. The monsoon
would render many routes impassable, and therefore set an absolute time
limitation. Engaging participants willingly in the enquiry would be the key to
success, and several tactics would be employed to enhance the success of this,
most importantly enlisting the support of local community volunteers in each
study site. CONCLUSION: Anticipating problems in advance of investing substantial
resources in a large nationwide epidemiological study in Nepal was a sensible
precaution. The difficulties could be resolved or circumvented without expected
compromise in scientific quality. Expert consensus was an effective means of
achieving this outcome.
PMID- 25127663
TI - Phenethyl isothiocyanate upregulates death receptors 4 and 5 and inhibits
proliferation in human cancer stem-like cells.
AB - BACKGROUND: The cytokine TRAIL (tumor necrotic factor-related apoptosis-inducing
ligand) selectively induces apoptosis in cancer cells, but cancer stem cells
(CSCs) that contribute to cancer-recurrence are frequently TRAIL-resistant. Here
we examined hitherto unknown effects of the dietary anti-carcinogenic compound
phenethyl isothiocyanate (PEITC) on attenuation of proliferation and
tumorigenicity and on up regulation of death receptors and apoptosis in human
cervical CSC. METHODS: Cancer stem-like cells were enriched from human cervical
HeLa cell line by sphere-culture method and were characterized by CSC-specific
markers' analyses (flow cytometry) and Hoechst staining. Cell proliferation
assays, immunoblotting, and flow cytometry were used to assess anti-proliferative
as well as pro-apoptotic effects of PEITC exposure in HeLa CSCs (hCSCs).
Xenotransplantation study in a non-obese diabetic, severe combined
immunodeficient (NOD/SCID) mouse model, histopathology, and ELISA techniques were
further utilized to validate our results in vivo. RESULTS: PEITC attenuated
proliferation of CD44(high/+)/CD24(low/-), stem-like, sphere-forming
subpopulations of hCSCs in a concentration- and time-dependent manner that was
comparable to the CSC antagonist salinomycin. PEITC exposure-associated up
regulation of cPARP (apoptosis-associated cleaved poly [ADP-ribose] polymerase)
levels and induction of DR4 and DR5 (death receptor 4 and 5) of TRAIL signaling
were observed. Xenotransplantation of hCSCs into mice resulted in greater
tumorigenicity than HeLa cells, which was diminished along with serum hVEGF-A
(human vascular endothelial growth factor A) levels in the PEITC-pretreated hCSC
group. Lung metastasis was observed only in the hCSC-injected group that did not
receive PEITC-pretreatment. CONCLUSIONS: The anti-proliferative effects of PEITC
in hCSCs may at least partially result from up regulation of DR4 and possibly DR5
of TRAIL-mediated apoptotic pathways. PEITC may offer a novel approach for
improving therapeutic outcomes in cancer patients.
PMID- 25127665
TI - Plasma and platelet serotonin concentrations in healthy dogs and dogs with
myxomatous mitral valve disease.
AB - OBJECTIVES: Serotonin has been implicated in canine myxomatous mitral valve
disease (MMVD); however, the sources of serotonin have not been fully elucidated.
This study compared the concentration of serotonin in plasma and platelets of
normal healthy small breed dogs with predisposition to MMVD and dogs with
naturally occurring MMVD. ANIMALS: 43 small-breed client-owned dogs with an
approximate weight of <10 kg and age of 6 years or above were divided into 2
groups: a healthy control group (n = 20) and a group with echocardiographic
evidence of MMVD (n = 23). METHODS: 5 ml samples of blood were collected. Plasma
and platelets were separated by centrifugation and assayed for serotonin measured
by enzyme linked immunosorbent assay (ELISA). RESULTS: Median plasma serotonin
concentration was not significantly different (p = 0.3630) between normal healthy
dogs (3.7 ng/ml) and dogs with MMVD (4.3 ng/ml). Males had higher plasma
serotonin concentration than females (4.7 and 2.9 ng/ml respectively, p =
0.0043). Platelet serotonin concentration was not different between healthy dogs
and dogs with MMVD (128.6 ng/109 platelets and 176.6 ng/109 platelets
respectively, p = 0.4575). Age, echocardiographic indices and platelet count
showed no correlation with plasma or platelet serotonin concentration.
CONCLUSIONS: Circulating plasma serotonin is unlikely a major source of serotonin
signaling in canine MMVD. Platelets could be a source of serotonin in canine MMVD
through platelet adhesion to the mitral valve; however, the amount of serotonin
stored in platelets of healthy dogs and dogs with MMVD is not different.
PMID- 25127666
TI - Echocardiographic and radiographic findings in a cohort of healthy adult green
iguanas (Iguana iguana).
AB - OBJECTIVES: To describe characteristics of echocardiography and cranial coelomic
radiography in a cohort of iguanas. ANIMALS: Twenty apparently healthy adult
green iguanas (Iguana iguana) from a reptile sanctuary. METHODS: Physical
examination, radiography, two-dimensional and color Doppler echocardiography were
performed to assess cardiac structures and function, and any related normal or
abnormal findings were recorded. RESULTS: Echocardiographic examination was
possible without sedation and allowed visualization of the great vessels, atria,
and ventricle. Some structures could not be evaluated in a minority of the
iguanas due to individual differences in bony conformation and imaging quality.
Suspected abnormal echocardiographic findings in 3 iguanas included pericardial
effusion (n = 1) and enlarged caudal vena cava and/or sinus venosus (n = 2).
Objective measurements were repeatable as assessed by within-subject coefficient
of variation, and reliable as assessed by intra-observer intraclass correlation
coefficient. Left atrial and ventricular measurements were significantly
correlated with body weight. Valve regurgitation was common, with
atrioventricular valve regurgitation present in 53% (9/17) and aortic or pulmonic
valve regurgitation in 71% (12/17) of otherwise normal iguanas. A heart murmur
was not appreciated during examination of any of the iguanas. Heart size cannot
be measured radiographically due to superimposition and silhouetting of other
coelomic structures. Echocardiographic or radiographic findings consistent with
mineralization of the great vessels were present in 76% of iguanas (13/17).
CONCLUSIONS: Echocardiography in iguanas is well tolerated without sedation and
allowed both subjective evaluation and structural measurements. Valve
regurgitation and great vessel mineralization were commonly observed in this
cohort of apparently healthy adult iguanas.
PMID- 25127667
TI - The effects of health coaching on adult patients with chronic diseases: a
systematic review.
AB - OBJECTIVE: The aim of this systematic review was to describe the effects of
health coaching on adult patients with chronic diseases. METHODS: The reviewers
searched electronic databases and performed a manual search for studies published
from 2009 to 2013. The inclusion criteria covered health coaching for adults with
chronic diseases by health care professionals. The studies were original,
randomized controlled trials or quasi-experimental designs. RESULTS: Thirteen
studies were selected using the inclusion criteria. The results indicate that
health coaching produces positive effects on patients' physiological, behavioral
and psychological conditions and on their social life. In particular,
statistically significant results revealed better weight management, increased
physical activity and improved physical and mental health status. CONCLUSION:
Health coaching improves the management of chronic diseases. Further research
into the cost-effectiveness of health coaching and its long-term effectiveness
for chronic diseases is needed. Practice implications Health care professionals
play key roles in promoting healthy behavior and motivating good care for adults
with chronic diseases. Health coaching is an effective patient education method
that can be used to motivate and take advantage of a patient's willingness to
change their life style and to support the patient's home-based self-care.
PMID- 25127668
TI - Delayed left ventricular apical thrombus formation following discontinuation of
dual anti-platelet therapy.
AB - Delayed de novo left ventricular apical thrombus following a distant antero
apical myocardial infarction has to our knowledge not been previously reported.
Herein we describe a patient who developed an apical thrombus 18 months after his
initial infarct following cessation of dual anti-platelet therapy for a traumatic
subdural haematoma requiring surgical evacuation.
PMID- 25127669
TI - Cardiac vignette: isolated pulmonary regurgitation.
AB - Isolated pulmonary regurgitation (PR) is a rare occurrence with only a handful of
documented cases worldwide. Though usually well tolerated in childhood, chronic
PR can eventually lead to RV dysfunction and ventricular arrhythmias. In this
cardiac vignette, we describe a case of isolated PR in a young female presenting
with syncope and explore the natural history, different investigative modalities
as well as issues in clinical management of this rare condition.
PMID- 25127670
TI - Mitochondrial DNA has three major variations.
PMID- 25127671
TI - Molecular cloning, characterization and tissue distribution of two ostrich beta
defensins: AvBD2 and AvBD7.
AB - Avian beta-defensins (AvBDs) are a family of small antimicrobial peptides that
play important roles in the innate immunity of birds. Herein, we report on two
new ostrich AvBD genes, AvBD2 and AvBD7, which were isolated from the bone marrow
of ostriches (Struthio camelus). The coding regions of ostrich AvBD2 and AvBD7
comprised 195 bp and 201bp, which encoded 64 and 66 amino acids, respectively.
Homology analysis showed that ostrich AvBD2 had the highest similarity (up to
86%) with the swan goose (Anser cygnoides) AvBD2, while ostrich AvBD7 shared the
highest similarity (up to 81%) with chicken AvBD7. Analysis of the codon-usage
bias showed that the two ostrich AvBDs had different codon-usage patterns from
other AvBDs. The two synthetic AvBD peptides exhibited antibacterial activities
against both Gram-positive and Gram-negative bacteria, and these activities
decreased significantly in the presence of 100mM NaCl (P<0.01). Real-time reverse
transcription-polymerase chain reaction analysis showed that AvBD2 and AvBD7 were
widely expressed at different levels in 17 different tissues. This is the first
report of the nucleotide sequences of ostrich AvBDs. Further investigations of
these two AvBDs may help us to gain new insights into the immune defense system
of the ostrich and to make subsequent therapeutic use of ostrich defensins.
PMID- 25127672
TI - Double incretin receptor knock-out (DIRKO) mice present with alterations of
trabecular and cortical micromorphology and bone strength.
AB - A role for gut hormone in bone physiology has been suspected. We evidenced
alterations of microstructural morphology (trabecular and cortical) and bone
strength (both at the whole-bone--and tissue-level) in double incretin receptor
knock-out (DIRKO) mice as compared to wild-type littermates. These results
support a role for gut hormones in bone physiology. INTRODUCTION: The two
incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like
peptide-1 (GLP-1), have been shown to control bone remodeling and strength.
However, lessons from single incretin receptor knock-out mice highlighted a
compensatory mechanism induced by elevated sensitivity to the other gut hormone.
As such, it is unclear whether the bone alterations observed in GIP or GLP-1
receptor deficient animals resulted from the lack of a functional gut hormone
receptor, or by higher sensitivity for the other gut hormone. The aims of the
present study were to investigate the bone microstructural morphology, as well as
bone tissue properties, in double incretin receptor knock-out (DIRKO) mice.
METHODS: Twenty-six-week-old DIRKO mice were age- and sex-matched with wild-type
(WT) littermates. Bone microstructural morphology was assessed at the femur by
microCT and quantitative X-ray imaging, while tissue properties were investigated
by quantitative backscattered electron imaging and Fourier-transformed infrared
microscopy. Bone mechanical response was assessed at the whole-bone- and tissue
level by 3-point bending and nanoindentation, respectively. RESULTS: As compared
to WT animals, DIRKO mice presented significant augmentations in trabecular bone
mass and trabecular number whereas bone outer diameter, cortical thickness, and
cortical area were reduced. At the whole-bone-level, yield stress, ultimate
stress, and post-yield work to fracture were significantly reduced in DIRKO
animals. At the tissue-level, only collagen maturity was reduced by 9 % in DIRKO
mice leading to reductions in maximum load, hardness, and dissipated energy.
CONCLUSIONS: This study demonstrated the critical role of gut hormones in
controlling bone microstructural morphology and tissue properties.
PMID- 25127673
TI - A systematic review of complicated diverticulitis in post-transplant patients.
AB - BACKGROUND: Immunosuppression could increase the complication rate in patients
with acute diverticulitis. This would justify a low threshold for elective
sigmoid resection in these patients after an episode of diverticulitis. Well
documented groups of immunocompromised patients are transplant patients, in which
many prospective studies have been conducted. OBJECTIVES: The aim of this
systematic review is to assess the incidence of complicated diverticulitis in
post-transplant patients. DATA SOURCE: We searched MEDLINE, EMBASE, CINAHL, and
Cochrane databases for papers published between January 1966 and January 2014.
STUDY SELECTION AND INTERVENTION: Publications dealing with post-transplant
patients and left-sided diverticulitis were eligible for inclusion. The following
exclusion criteria were used for study selection: abstracts, case-series and non
English articles. MAIN OUTCOME MEASURES: Primary outcome measure was the
incidence of complicated diverticulitis. Secondary outcome was the incidence of
acute diverticulitis and the proportion of complicated diverticulitis. Pooling of
data was only performed when more than five reported on the outcome of interest
with comparable cohorts. Only studies describing proportion of complicated
diverticulitis and renal transplant studies were eligible for pooling data.
RESULTS: Seventeen articles met the inclusion criteria. Nine renal transplant
cohorts, four mixed lung-heart-heart lung transplant cohorts, two heart
transplant cohorts, and two lung cohorts. A total of 11,966 post-transplant
patients were included in the present review. Overall incidence of complicated
diverticulitis in all transplantation studies ranged from 0.1 to 3.5%. Nine
studies only included renal transplant patients. Pooled incidence of complicated
diverticulitis in these patients was 1.0% (95% CI 0.6 to 1.5%). Ten studies
provided proportion of complicated diverticulitis. Pooled incidence of acute
diverticulitis in these studies was 1.7% (95% CI 1.0 to 2.7%). Pooled proportion
of complicated diverticulitis among these patients was 40.1% (95% CI 32.2 to
49.7%). All studies were of moderate quality using the MINORS scoring scale.
CONCLUSION: The incidence of complicated diverticulitis is about one in 100
transplant patients. Additionally when a transplant patient develops an episode
of acute diverticulitis, a high proportion of patients have a complicated disease
course.
PMID- 25127674
TI - Changes in the loading conditions induced by vagal stimulation modify the
myocardial infarct size through sympathetic-parasympathetic interactions.
AB - In a previous research, we described that vagal stimulation increases the infarct
size by sympathetic co-activation. The aim of this study was to determine if
hemodynamic changes secondary to the vagal stimulation are able to activate
sympathetic compensatory neural reflexes, responsible for increasing the infarct
size. A second goal was to determine if intermittent vagal stimulation avoids
sympathetic activation and reduces infarct size by muscarinic activation of the
Akt/glycogen synthase kinase 3 beta (GSK-3beta) pathway. Rabbits were subjected
to 30 min of regional myocardial ischemia and 3 h of reperfusion without vagal
stimulation, or the following protocols of right vagus nerve stimulation for 10
min before ischemia: (a) continuous vagal stimulation and (b) intermittent vagal
stimulation (cycles of 10 s ON/50 s OFF). Continuous vagal stimulation increased
the infarct size (70.7 +/- 4.3 %), even after right vagal section (68.6 +/- 4.1
%) compared with control group (52.0 +/- 3.7 %, p < 0.05). Bilateral vagotomy,
pacing, and esmolol abolished the deleterious effect, reaching an infarct size of
43.3 +/- 5.1, 43.5 +/- 2.1, and 46.0 +/- 4.6 % (p < 0.05), respectively.
Intermittent stimulation reduced the infarct size to 29.8 +/- 3.0 % (p < 0.05 vs
I/R). This effect was blocked with atropine (50.2 +/- 3.6 %, p < 0.05).
Continuous vagal stimulation induced bradycardia and increased the loading
conditions and wall stretching of the atria. These changes provoked the co
activation reflex of the sympathetic nervous system, observed by the rise in
plasmatic catecholamine levels, which increased the infarct size. Sympathetic co
activation was abolished by continuous vagal stimulation with constant heart rate
or parasympathetic deafferentation. Intermittent vagal stimulation attenuated the
sympathetic tone and reduced the infarct size by the muscarinic activation of the
Akt pathway and GSK-3beta inhibition. Continuous stimulation only phosphorylated
Akt and GSK-3beta when esmolol was administered.
PMID- 25127676
TI - An effector gene hopA1 influences on virulence, host specificity, and lifestyles
of Pseudomonas cichorii JBC1.
AB - Pseudomonas cichorii is a devastating pathogen which infects a wide range of
ornamental as well as agricultural crops worldwide. Characterization of virulence
genes helps to understand pathogens' infection processes, which may lead to
development of resistant crops. For functional validation of novel genes, we re
constructed pUCP18 vector with lambda phage red operon and sacB gene
(pUCP18_RedS), which simplified conventional marker exchange system. The effector
gene hopA1 of P. cichorii JBC1 was marker exchanged with PCR product of kanamycin
gene flanked by hopA1 flanking region using pUCP18_RedS. The virulence and
internal growth of hopA1 defective mutant (DeltahopA1) in tomato seedlings was
significantly reduced compared to wild type (WT) and hopA1 complemented strain
(DeltahopA1::phopA1). The analysis on role of hopA1 in host range revealed that
P. cichorii was hopA1-dependent to infect cabbage, tomato, soybean, hot pepper,
and cucumber, but not melon and eggplant. Despite the similarity in growth
pattern, the biofilm formation and swarming motility of DeltahopA1 were
significantly reduced compared to WT and DeltahopA1::phopA1. The results of this
study indicate that hopA1 plays a significant role not only in virulence and host
specificity, but also motility and biofilm formation of P. cichorii which may
influence the infection processes.
PMID- 25127675
TI - Kir1.1 (ROMK) and Kv7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid
secretion: importance of functional Kir1.1.
AB - Potassium channels comprise the apical leak pathway supplying extracellular K(+)
for exchange with protons by the gastric H(+), K(+)-ATPase and provide potential
therapeutic targets for inhibiting gastric acid secretion. The Kir1.1 (ROMK)
potassium channel mediates the high capacity K(+) recycling necessary for NaCl
reabsorption in the thick ascending limb of the kidney, and this channel exhibits
functional and regulatory characteristic well suited for K(+) recycling by
gastric parietal cells. We report here that Kir1.1 channels are required for
gastric acid secretion and that this channel participates with Kv7.1
(KCNQ1/KvLQT1) in the potassium recycling process. We show that Kir1.1
colocalizes with the beta-subunit of H(+), K(+)-ATPase in gastric parietal cells
of Kir1.1 wild-type mice. In Kir1.1-deficient mice, gastric mucosal morphology,
as well as parietal cell number, proliferation index, and ultrastructure were
normal but secretagogue-stimulated gastric acid secretion in whole stomach and
perfused gastric glands was absent. Luminal application of potassium-restored
acid secretion in perfused gastric glands from Kir1.1-deficient as well as barium
blocked wild-type mice. In wild-type mice, both luminal Tertiapin-Q, an inhibitor
of Kir1.1, as well as XE991, an inhibitor of Kv7.1, reduced proton secretion. We
propose that Kir1.1 and Kv7.1 channels collaborate in potassium and current
recycling across the apical pole of parietal cells.
PMID- 25127678
TI - Converging goals of treatment of inflammatory bowel disease from clinical trials
and practice.
AB - It is important to have clear goals for treating inflammatory bowel disease in
clinical practice and in research. Conventional end points for trials in
ulcerative colitis and Crohn's disease have been based on composite indices, such
as the Mayo Clinic Score and the Crohn's Disease Activity Index; these indices
incorporate symptoms, signs, and findings from laboratory tests and sometimes
endoscopic assessments. Although definitions of clinical response and remission
have been based on these indices for regulatory purposes, they are difficult to
apply to practice because they are complex and not intuitive to clinicians. This
has caused a disconnect between clinical trials and practice. Recently, the use
of composite indices in trials has been reevaluated in Food and Drug
Administration-sponsored Gastroenterology Regulatory Endpoints and the
Advancement of Therapeutics workshops due to concerns about the validity of the
indices. Alternative measures of outcome and definitions of response are being
developed. Patient-reported outcomes are psychometric instruments created and
defined by patients to quantify symptoms. A combination of end points, comprising
patient-reported outcomes and objective evaluation of inflammation by endoscopy,
offers a clinically meaningful and scientifically valid alternative to existing
composite indices. Unlike composite indices, response definitions based on
endoscopy and patient-reported outcomes can be readily applied in practice. This
convergence of outcome assessment in clinical trials and practice could expedite
implementation of "treat-to-target" algorithms, in which therapy is progressively
intensified until a specific treatment goal is reached. This approach could
improve patient care by reducing rates of disease-related complications, surgery,
and hospitalization.
PMID- 25127677
TI - Nicotine promotes initiation and progression of KRAS-induced pancreatic cancer
via Gata6-dependent dedifferentiation of acinar cells in mice.
AB - BACKGROUND & AIMS: Although smoking is a leading risk factor for pancreatic
ductal adenocarcinoma (PDAC), little is known about the mechanisms by which
smoking promotes initiation or progression of PDAC. METHODS: We studied the
effects of nicotine administration on pancreatic cancer development in
Kras(+/LSLG12Vgeo);Elas-tTA/tetO-Cre (Ela-KRAS) mice,
Kras(+/LSLG12D);Trp53+/LSLR172H;Pdx-1-Cre (KPC) mice (which express
constitutively active forms of KRAS), and C57/B6 mice. Mice were given nicotine
for up to 86 weeks to produce blood levels comparable with those of intermediate
smokers. Pancreatic tissues were collected and analyzed by immunohistochemistry
and reverse transcriptase polymerase chain reaction; cells were isolated and
assayed for colony and sphere formation and gene expression. The effects of
nicotine were also evaluated in primary pancreatic acinar cells isolated from
wild-type, nAChR7a(-/-), Trp53(-/-), and Gata6(-/-);Trp53(-/-) mice. We also
analyzed primary PDAC cells that overexpressed GATA6 from lentiviral expression
vectors. RESULTS: Administration of nicotine accelerated transformation of
pancreatic cells and tumor formation in Ela-KRAS and KPC mice. Nicotine induced
dedifferentiation of acinar cells by activating AKT-ERK-MYC signaling; this led
to inhibition of Gata6 promoter activity, loss of GATA6 protein, and subsequent
loss of acinar differentiation and hyperactivation of oncogenic KRAS. Nicotine
also promoted aggressiveness of established tumors as well as the epithelial
mesenchymal transition, increasing numbers of circulating cancer cells and their
dissemination to the liver, compared with mice not exposed to nicotine. Nicotine
induced pancreatic cells to acquire gene expression patterns and functional
characteristics of cancer stem cells. These effects were markedly attenuated in K
Ras(+/LSL-G12D);Trp53(+/LSLR172H);Pdx-1-Cre mice given metformin. Metformin
prevented nicotine-induced pancreatic carcinogenesis and tumor growth by up
regulating GATA6 and promoting differentiation toward an acinar cell program.
CONCLUSIONS: In mice, nicotine promotes pancreatic carcinogenesis and tumor
development via down-regulation of Gata6 to induce acinar cell dedifferentiation.
PMID- 25127679
TI - Equivalency of fecal immunochemical tests and colonoscopy in familial colorectal
cancer screening.
AB - BACKGROUND & AIMS: Colonoscopy is the recommended screening procedure for first
degree relatives of patients with colorectal cancer (CRC), but few studies have
compared its efficacy for CRC detection with that of other screening strategies.
We conducted a controlled randomized trial to compare the efficacy of repeated
fecal immunochemical tests (FITs) and colonoscopy in detecting advanced neoplasia
(advanced adenoma or CRC) in family members of patients with CRC. METHODS: In a
prospective study, 1918 first-degree relatives of patients with CRC were randomly
assigned (1:1 ratio) to receive a single colonoscopy examination or 3 FITs
(1/year for 3 years; OC-Sensor; cutoff >=10 MUg hemoglobin/g feces, corresponding
to 50 ng hemoglobin/mL buffer). The strategies were considered to be equivalent
if the 95% confidence interval of the difference for the detection of advanced
neoplasia was +/-3%. Follow-up analyses were performed to identify false-negative
FIT results and interval CRCs. RESULTS: Of all eligible asymptomatic first-degree
relatives, 782 were included in the colonoscopy group and 784 in the FIT group.
In the intention-to-screen analysis, advanced neoplasia was detected in 33 (4.2%)
and 44 (5.6%) first-degree relatives in the FIT and colonoscopy groups,
respectively (odds ratio = 1.41; 95% confidence interval: 0.88-2.26; P = .14). In
the per-protocol analysis, 28 first-degree relatives (3.9%) in the FIT group and
43 (5.8%) in the colonoscopy group had advanced neoplasia (odds ratio = 1.56; 95%
confidence interval: 0.95-2.56; P = .08). FIT missed 16 of 41 advanced adenomas
but no CRCs. The FIT strategy required endoscopic evaluation of 4-fold fewer
individuals to detect 1 advanced neoplasia than the colonoscopy strategy.
CONCLUSIONS: Repeated FIT screening (1/year for 3 years) detected all CRCs and
proved equivalent to colonoscopy in detecting advanced neoplasia in first-degree
relatives of patients with CRC. This strategy should be considered for
populations where compliance with FITs is higher than with colonoscopy.
ClinicalTrials.gov number: NCT01075633 (COLONFAM Study).
PMID- 25127680
TI - Increased intake of vegetables, but not fruit, reduces risk for hepatocellular
carcinoma: a meta-analysis.
AB - BACKGROUND & AIMS: The anti-cancer effects of vegetables and fruit have been
investigated extensively, but the association between vegetable and fruit
consumption and risk of hepatocellular carcinoma (HCC) has not been quantified.
We performed a meta-analysis of observational studies to clarify the association.
METHODS: We identified eligible studies, published from 1956 through May 31,
2014, by searching PubMed, Web of Science, and EMBASE. Random-effects models were
used to calculate summary relative risks (RRs) and dose-response analyses were
conducted to quantify associations. Heterogeneity among studies was evaluated
using Cochran's Q and I(2) statistics. RESULTS: A total of 19 studies involving
1,290,045 participants and 3912 cases of HCC were included in the meta-analysis.
The summary RR for HCC was 0.72 for individuals with high intake vs low intake of
vegetables (95% confidence interval [CI]: 0.63-0.83) and 0.92 with a daily
increase in vegetable intake (100 g/d) (95% CI: 0.88-0.95). Subgroup analyses
showed that this inverse association did not change regardless of history of
hepatitis, alcohol drinking, smoking, or energy intake. The summary RR for HCC
among individuals with high vs low intake of fruit was 0.93 (95% CI: 0.80-1.09),
and 0.99 with a daily increase in fruit intake (100 g/d) (95% CI: 0.94-1.05).
CONCLUSIONS: Based on a meta-analysis, increased intake of vegetables, but not
fruit, is associated with lower risk for HCC. The risk of HCC decreases by 8% for
every 100 g/d increase in vegetable intake. The findings should be confirmed by
future studies with validated questionnaires and strict control of confounders.
PMID- 25127681
TI - The effects of amphetamine, butorphanol, and their combination on cocaine self
administration.
AB - There have been recent calls to examine the efficacy of drug-combination
therapies in the treatment of substance use disorders. The purpose of the present
study was to examine the ability of a novel stimulant-opioid combination to
reduce cocaine self-administration, and to compare these effects to those of each
drug administered alone. To this end, male Long-Evans rats were implanted with
intravenous catheters and trained to self-administer cocaine under positive
reinforcement contingencies. Once self-administration was acquired, rats were
divided into four different groups and treated chronically for 20 days with (1)
saline, (2) the psychomotor stimulant and monoamine releaser amphetamine, (3) the
mu/kappa opioid agonist butorphanol, or (4) a combination of amphetamine and
butorphanol. During chronic treatment, cocaine self-administration was examined
on both fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement.
On the FR schedule, butorphanol significantly decreased cocaine self
administration, but this effect was not enhanced by amphetamine. On the PR
schedule, amphetamine and butorphanol non-significantly decreased cocaine self
administration when administered alone but significantly decreased cocaine self
administration when administered in combination. These data suggest that under
some conditions (e.g., when the response requirement of cocaine is high), a dual
stimulant-opioid pharmacotherapy may be more effective than a single-drug
monotherapy.
PMID- 25127682
TI - Neuroprotective effects of peroxisome proliferator-activated receptor alpha and
gamma agonists in model of parkinsonism induced by intranigral 1-methyl-4-phenyl
1,2,3,6-tetrahyropyridine.
AB - A large body of evidence suggests that peroxisome proliferator-activated receptor
(PPAR) agonists may improve some of the pathological features of Parkinson's
disease (PD). In the present study, we evaluated the effects of the PPAR-alpha
agonist fenofibrate (100mg/kg) and PPAR-gamma agonist pioglitazone (30mg/kg) in a
rat model of parkinsonism induced by intranigral 1-methyl-4-phenyl-1,2,3,6
tetrahyropyridine (MPTP). Male Wistar rats were pretreated with both drugs for 5
days and received an infusion of MPTP. The experiments were divided into two
parts. First, 1, 7, 14, and 21 days after surgery, the animals were submitted to
the open field test. On days 21 and 22, the rats were subjected to the forced
swim test and two-way active avoidance task. In the second part of the study, 24h
after neurotoxin administration, immunohistochemistry was performed to assess
tyrosine hydroxylase activity. The levels of dopamine and its metabolites in the
striatum were determined using high-performance liquid chromatography, and
fluorescence detection was used to assess caspase-3 activation in the substantia
nigra pars compacta (SNpc). Both fenofibrate as pioglitazone protected against
hypolocomotion, depressive-like behavior, impairment of learning and memory, and
dopaminergic neurodegeneration caused by MPTP, with dopaminergic neuron loss of
approximately 33%. Fenofibrate and pioglitazone also protected against the
increased activation of caspase-3, an effector enzyme of the apoptosis cascade
that is considered one of the pathological features of PD. Thus, PPAR agonists
may contribute to therapeutic strategies in PD.
PMID- 25127683
TI - Mice lacking TrkB in parvalbumin-positive cells exhibit sexually dimorphic
behavioral phenotypes.
AB - Activity-dependent brain-derived neurotrophic factor (BDNF) signaling through
receptor tyrosine kinase B (TrkB) is required for cued fear memory consolidation
and extinction. Although BDNF is primarily secreted from glutamatergic neurons,
TrkB is expressed by other genetically defined cells whose contributions to the
behavioral effects of BDNF remain poorly understood. Parvalbumin (PV)-positive
interneurons, which are highly enriched in TrkB, are emerging as key regulators
of fear memory expression. We therefore hypothesized that activity-dependent BDNF
signaling in PV-interneurons may modulate emotional learning. To test this
hypothesis, we utilized the LoxP/Cre system for conditional deletion of TrkB in
PV-positive cells to examine the impact of cell-autonomous BDNF signaling on
Pavlovian fear conditioning and extinction. However, behavioral abnormalities
indicative of vestibular dysfunction precluded the use of homozygous conditional
knockouts in tests of higher cognitive functioning. While vestibular dysfunction
was apparent in both sexes, female conditional knockouts exhibited an exacerbated
phenotype, including extreme motor hyperactivity and circling behavior, compared
to their male littermates. Heterozygous conditional knockouts were spared of
vestibular dysfunction. While fear memory consolidation was unaffected in
heterozygotes of both sexes, males exhibited impaired extinction consolidation
compared to their littermate controls. Our findings complement evidence from
human and rodent studies suggesting that BDNF signaling promotes consolidation of
extinction and point to PV-positive neurons as a discrete population that
mediates these effects in a sex-specific manner.
PMID- 25127685
TI - Centrally-administered oxytocin promotes preference for familiar objects at a
short delay in ovariectomized female rats.
AB - Oxytocin has been previously associated with social attachment behaviors in
various species, however, most studies focused on partner preference in the
socially-monogamous prairie vole. In these, oxytocin treatment was shown to
promote partner preference, such that females receiving either central or
pulsatile peripheral administration would spend more time with a familiar male.
This behavioral outcome was blocked by oxytocin receptor antagonist treatment.
The aim of the current study was to further explore the preference-inducing
properties of oxytocin by examining its effects on object preference on
ovariectomized female rats. In other words, we assessed whether these effects
would apply to objects and if they would be persistent across species. Eight rats
were infused with oxytocin into the left ventricle and object preference was
assessed at two delays: 30min and 4h. At the 30min delay, oxytocin-treated
animals showed preference for the familiar object, whereas saline-treated
controls exhibited preference for the novel object. At the 4h delay, both groups
showed novel-object preference. Our findings show that oxytocin modulates object
preference in the female rat at a shorter delay, similar to the findings from
partner-preference studies in the prairie vole, suggesting that the mechanisms
driving object preference might be in part similar to those responsible for
partner preference.
PMID- 25127684
TI - Tolerance to the locomotor-activating effects of 3,4
methylenedioxymethamphetamine (MDMA) predicts escalation of MDMA self
administration and cue-induced reinstatement of MDMA seeking in rats.
AB - Pre-clinical studies of individual differences in addiction vulnerability have
been increasing over recent years, but the amphetamine derivative 3,4
methylenedioxymethamphetamine (MDMA; ecstasy) has received relatively little
attention in this regard. Previously, we reported large individual differences
both in rats' initial behavioral response to experimenter-administered MDMA and
their degree of behavioral sensitization to repeated administration. To determine
whether these differences could predict subsequent patterns of MDMA-taking or
seeking behaviors we used the self-administration-extinction-reinstatement model
to examine addiction-like behavior (i.e., escalation of MDMA self-administration
and cue-induced reinstatement of MDMA seeking) in rats a priori characterized for
either locomotor sensitization or tolerance to MDMA. Rats that developed
tolerance to the locomotor-activating effects of MDMA had a significantly larger
locomotor response to the first MDMA injection relative to rats that developed
sensitization. Importantly, rats that developed tolerance subsequently displayed
an escalation of MDMA self-administration over days, as well as clear cue-induced
reinstatement of MDMA seeking following extinction. Conversely, rats that
developed locomotor sensitization to MDMA subsequently maintained relatively
stable levels of MDMA self-administration over days and showed no cue-induced
reinstatement of MDMA seeking. These results show that differences in the level
of psychomotor activation following acute and repeated MDMA administration can
reliably predict two important addiction-like behaviors in rats, which may have
implications in the prediction of compulsive MDMA use in humans.
PMID- 25127686
TI - Rapid bio-methanation of syngas in a reverse membrane bioreactor: membrane
encased microorganisms.
AB - The performance of a novel reverse membrane bioreactor (RMBR) with encased
microorganisms for syngas bio-methanation as well as a co-digestion process of
syngas and organic substances was examined. The sachets were placed in the
reactors and examined in repeated batch mode. Different temperatures and short
retention time were studied. The digesting sludge encased in the PVDF membranes
was able to convert syngas into methane at a retention time of 1 day and
displayed a similar performance as the free cells in batch fermentation. The co
digestion of syngas and organic substances by the RMBR (the encased cells) showed
a good performance without any observed negative effects. At thermophilic
conditions, there was a higher conversion of pure syngas and co-digestion using
the encased cells compared to at mesophilic conditions.
PMID- 25127687
TI - In vivo anti-hyperlipidemic activity of the triterpene from the stem bark of
Protorhus longifolia (Benrh) Engl.
AB - BACKGROUND: Hyperlipidemia, a metabolic disorder of lipids, is a well known risk
factor of cardiovascular events and metabolic syndrome. In this study, the in
vivo lipid-lowering activity of the triterpene (Methyl-3beta-hydroxylanosta-9,24
dien-21-oate), isolated from the stem bark of Protorhus longifolia, in high fat
diet (HFD)-induced hyperlipidemic rats was investigated. METHODS: Structure of
the isolated compound was established and confirmed based on spectral (NMR, HRMS,
IR) data analysis. Rats were divided into two groups; normal group (fed the
normal commercial rats' chow) and the HFD group. After 21 days of experimental
period on their respective diets, the HFD rats were sub-divided into 4 groups of
six rats per group. Two of the HFD groups were orally treated with the triterpene
(100 and 200 mg/kg body weight) for 15 days. At the end of the experimental
periods, the rats were sacrificed and blood samples were collected for
biochemical assays. RESULTS: The results show that there were significant
increases in total serum cholesterol (TC, 15.72 mmol/L) and low-density
lipoprotein cholesterol (LDL-c, 7.41 mmol/L) with a reduction in high-density
lipoprotein cholesterol (HDL-c, 14.75 mmol/L) in HFD-induced hyperlipidemic rats
after 21 days. Oral administration of the triterpene (100 mg/kg.bw and 200
mg/kg.bw) for a period of 15 days resulted in significant lowering of the levels
of TC (7.51 mmol/L) and LDL-c (4.46 mmol/L) with an increase in HDL-c (47.3
mmol/L) in HFD-induced hyperlipidemic rats. Significant decrease in atherogenic
index and coronary risk index by the triterpene was observed in HFD-induced
hyperlipidemic rats. CONCLUSIONS: The triterpene could effectively reduce or
control the amount of serum cholesterol and LDL. It is apparent that the compound
could contribute to new formulation with significant hypolipidemic effects.
PMID- 25127688
TI - Spatial-explicit modeling of social vulnerability to malaria in East Africa.
AB - BACKGROUND: Despite efforts in eradication and control, malaria remains a global
challenge, particularly affecting vulnerable groups. Despite the recession in
malaria cases, previously malaria free areas are increasingly confronted with
epidemics as a result of changing environmental and socioeconomic conditions.
Next to modeling transmission intensities and probabilities, integrated spatial
methods targeting the complex interplay of factors that contribute to social
vulnerability are required to effectively reduce malaria burden. We propose an
integrative method for mapping relative levels of social vulnerability in a
spatially explicit manner to support the identification of intervention measures.
METHODS: Based on a literature review, a holistic risk and vulnerability
framework has been developed to guide the assessment of social vulnerability to
water-related vector-borne diseases (VBDs) in the context of changing
environmental and societal conditions. Building on the framework, this paper
applies spatially explicit modeling for delineating homogeneous regions of social
vulnerability to malaria in eastern Africa, while taking into account expert
knowledge for weighting the single vulnerability indicators. To assess the
influence of the selected indicators on the final index a local sensitivity
analysis is carried out. RESULTS: Results indicate that high levels of malaria
vulnerability are concentrated in the highlands, where immunity within the
population is currently low. Additionally, regions with a lack of access to
education and health services aggravate vulnerability. Lower values can be found
in regions with relatively low poverty, low population pressure, low conflict
density and reduced contributions from the biological susceptibility domain.
Overall, the factors characterizing vulnerability vary spatially in the region.
The vulnerability index reveals a high level of robustness in regard to the final
choice of input datasets, with the exception of the immunity indicator which has
a marked impact on the composite vulnerability index. CONCLUSIONS: We introduce a
conceptual framework for modeling risk and vulnerability to VBDs. Drawing on the
framework we modeled social vulnerability to malaria in the context of global
change using a spatially explicit approach. The results provide decision makers
with place-specific options for targeting interventions that aim at reducing the
burden of the disease amongst the different vulnerable population groups.
PMID- 25127689
TI - An improved recombinant Fab-immunotoxin targeting CD22 expressing malignancies.
AB - Moxetumomab pasudotox (HA22) is a recombinant immunotoxin, now in clinical
trials, that combines an anti-CD22-Fv with a 38-kDa fragment of Pseudomonas
exotoxin A. To produce a less immunogenic molecule without reducing the half-life
in circulation, we constructed LMB11 combining an anti-CD22 Fab with a less
immunogenic version of PE38. We found that LMB11 retains full activity toward
CD22-expressing cells. In mice, the half-life of LMB11 is 29 min and the
antitumor activity of LMB11 is better than that of HA22. Because it can be safely
given at much higher doses, LMB11 produced complete tumor remissions in 7/7 mice.
PMID- 25127691
TI - A generic approach to post-column refocusing in liquid chromatography.
AB - To increase detection sensitivity in liquid chromatography, a generic post-column
refocusing strategy has been developed to enrich (target) analytes prior to
detection. In this strategy, after separation on the analytical column, the
analytes are led to a trap column preferably containing a stationary phase with
strong retentive properties (e.g. silica C30). They are then eluted using a
strong solvent in a backward-elution mode. A first key element of the proposed
strategy is that the trapping time should be at least equal to the time the front
of the remobilization solvent needs to cover the entire length of the trap
column, divided by the ratio of the flow rates used for trapping and
remobilization. This condition is independent of the retention properties of the
analytes in the trapping and remobilization solvent. Another essential element is
the addition of a third solvent (isopropanol in the present case) to the
remobilization solvent to overcome viscous-fingering effects caused by the
viscosity difference between the trap and the remobilization solvents. The
potential of the proposed post-column refocusing strategy is demonstrated for an
isocratic separation of KI (t0 marker), an antibiotic (sulfamethazine), and
acetophenone as a case study. Using optimized remobilization conditions a maximum
signal-enhancement factor of 8 was achieved. Higher enhancement factors using a
remobilization solvent with slightly higher elution strength were prohibited by
disturbances of the UV background signal.
PMID- 25127690
TI - The prognostic importance of polypharmacy in older adults treated for acute
myelogenous leukemia (AML).
AB - We retrospectively evaluated the prognostic significance of polypharmacy and
inappropriate medication use among 150 patients >60 years of age receiving
induction chemotherapy for acute myelogenous leukemia (AML). After adjustment for
age and comorbidity, increased number of medications at diagnosis (>= 4 versus <=
1) was associated with increased 30-day mortality (OR=9.98, 95% CI=1.18-84.13),
lower odds of complete remission status (OR=0.20, 95% CI=0.06-0.65), and higher
overall mortality (HR=2.13, 95% CI=1.15-3.92). Inappropriate medication use
(classified according to Beers criteria) was not significantly associated with
clinical outcomes. Polypharmacy warrants further study as a modifiable marker of
vulnerability among older adults with AML.
PMID- 25127692
TI - Optimization of reactive simulated moving bed systems with modulation of feed
concentration for production of glycol ether ester.
AB - In this article, we extend the simulated moving bed reactor (SMBR) mode of
operation to the production of propylene glycol methyl ether acetate (DOWANOLTM
PMA glycol ether) through the esterification of 1-methoxy-2-propanol (DOWANOLTM
PM glycol ether) and acetic acid using AMBERLYSTTM 15 as a catalyst and
adsorbent. In addition, for the first time, we integrate the concept of
modulation of the feed concentration (ModiCon) to SMBR operation. The performance
of the conventional (constant feed) and ModiCon operation modes of SMBR are
analyzed and compared. The SMBR processes are designed using a model based on a
multi-objective optimization approach, where a transport dispersive model with a
linear driving force for the adsorption rate has been used for modeling the SMBR
system. The adsorption equilibrium and kinetics parameters are estimated from the
batch and single column injection experiments by the inverse method. The multiple
objectives are to maximize the production rate of DOWANOLTM PMA glycol ether,
maximize the conversion of the esterification reaction and minimize the
consumption of DOWANOLTM PM glycol ether which also acts as the desorbent in the
chromatographic separation. It is shown that ModiCon achieves a higher
productivity by 12-36% over the conventional operation with higher product purity
and recovery.
PMID- 25127693
TI - A let-7 microRNA polymorphism in the KRAS 3'-UTR is prognostic in oropharyngeal
cancer.
AB - INTRODUCTION: This study aimed to investigate the effect of genetic polymorphisms
in miRNA sequences, miRNA target genes and miRNA processing genes as additional
biomarkers to HPV for prognosis in oropharyngeal squamous cell carcinoma (OPSCC)
patients. Secondarily, the prevalence of HPV-associated OPSCC in a European
cohort was mapped. METHODS: OPSCC patients (n=122) were genotyped for ten genetic
polymorphisms in pre-miRNAs (pre-mir-146a, pre-mir-196a2), in miRNA biosynthesis
genes (Drosha, XPO5) and in miRNA target genes (KRAS, SMC1B). HPV status was
assessed by p16 immunohistochemistry (IHC) and high-risk HPV in situ
hybridization (ISH) or by p16 IHC and PCR followed by enzyme-immunoassay (EIA).
Overall and disease specific survival were analysed using Kaplan-Meier plots (log
rank test). Cox proportional hazard model was used to calculate hazard ratios
(HR). RESULTS: The overall HPV prevalence rate in our Belgian/Dutch cohort was
27.9%. Patients with HPV(+) tumours had a better 5-years overall survival (78%
vs. 46%, p=0.001) and a better 5-years disease specific survival (90% vs. 70%,
p=0.016) compared to patients with HPV(-) tumours. In multivariate Cox analysis
including clinical, treatment and genetic parameters, HPV negativity (HR=3.89,
p=0.005), advanced T-stage (HR=1.81, p=0.050), advanced N-stage (HR=5.86,
p=0.001) and >10 pack-years of smoking (HR=3.45, p=0.012) were significantly
associated with reduced overall survival. The variant G-allele of the KRAS-LCS6
polymorphism was significantly associated with a better overall survival
(HR=0.40, p=0.031). CONCLUSIONS: Our results demonstrate that OPSCC patients with
the KRAS-LCS6 variant have a better outcome and suggest that this variant may be
used as a prognostic biomarker for OPSCC.
PMID- 25127694
TI - Aniseikonia following pneumatic retinopexy for rhegmatogenous retinal detachment.
AB - PURPOSE: To evaluate the characteristics of aniseikonia in patients with
rhegmatogenous retinal detachment (RD) after pneumatic retinopexy. DESIGN:
Prospective, interventional case series study. METHODS: Thirty patients who had
undergone pneumatic retinopexy as the initial procedure for rhegmatogenous
retinal detachment were selected for this study. The principal outcomes included
visual acuity, postoperative aniseikonia measured by the New Aniseikonia Test,
anatomical success, and measurement of central retinal thickness using optical
coherence topography (OCT). These outcomes were measured postoperatively at 3, 6,
and 12 months. RESULTS: The median patient age was 37 years (range, 13-57 years),
with 17 cases of macula-off RD and 13 cases of macula-on RD. All of these
patients achieved anatomical success, proven by OCT after surgical repair. Three
months after pneumatic retinopexy, 18 patients (60.0%) developed micropsic
aniseikonia and aniseikonia was diagnosed in 15 patients (88.2%) in the macula
off RD group, leaving 2 patients (11.8%) unaffected. In the macula-on RD group, 3
patients (23.1%) were found to have aniseikonia, while 10 patients (76.9%) were
unaffected. The presence of aniseikonia was strongly linked to the difference in
central retinal thickness, between the operated eye and the fellow eye, measured
at 12 months postoperatively. CONCLUSION: Aniseikonia after pneumatic retinopexy
for rhegmatogenous RD may be related to the preoperative macular status. Macula
off RD patients had a higher incidence of aniseikonia, compared to macula-on RD
patients, following retina reattachment. There was a moderate to high correlation
between the grading of aniseikonia and the difference in central retinal
thickness.
PMID- 25127695
TI - Clinicopathological findings in abusive head trauma: analysis of 110 infant
autopsy eyes.
AB - PURPOSE: To investigate the histopathology in a large series of autopsy eyes from
children with abusive head trauma. DESIGN: Retrospective case-control series.
METHODS: One hundred and ten eyes from 55 autopsies examined at an academic
tertiary referral center over 21 years were tabulated for histopathology:
subdural hemorrhage in the optic nerve sheath, intrascleral hemorrhage, any
retinal hemorrhage, ora-extended hemorrhage, cherry hemorrhage, perimacular
ridge, and internal limiting membrane tear. Select tissues with cherry hemorrhage
were further examined by transmission electron microscopy. RESULTS: Sixty eyes
were identified as "abusive head trauma" (cases), 46 as "alternative cause"
(controls), and 4 as "abusive head trauma survivor". Cases were legally verified
or confirmed by confession in all except 1 case. All ocular histopathologic
observations from cases were similar or more frequent in infants younger than 16
months of age. When present, a cherry hemorrhage and perimacular ridge were most
often found together, and only with a torn internal limiting membrane. Both
abusive head trauma survivor cases demonstrated severe optic nerve atrophy and
macular ganglion cell loss. CONCLUSIONS: Younger infants may be even more
susceptible to damage from vitreomacular traction by rotational and/or
acceleration-deceleration forces. Identifying cherry hemorrhages may aid abusive
head trauma diagnosis. Survivor abusive head trauma pathology demonstrates
unique, irreversible macular and optic nerve damage.
PMID- 25127696
TI - The subject-fixated coaxially sighted corneal light reflex: a clinical marker for
centration of refractive treatments and devices.
AB - PURPOSE: To describe the inconsistencies in definition, application, and usage of
the ocular reference axes (optical axis, visual axis, line of sight, pupillary
axis, and topographic axis) and angles (angle kappa, lambda, and alpha) and to
propose a precise, reproducible, clinically defined reference marker and axis for
centration of refractive treatments and devices. DESIGN: Perspective. METHODS:
Literature review of papers dealing with ocular reference axes, angles, and
centration. RESULTS: The inconsistent definitions and usage of the current ocular
axes, as derived from eye models, limit their clinical utility. With a clear
understanding of Purkinje images and a defined alignment of the observer, light
source/fixation target, and subject eye, the subject-fixated coaxially sighted
corneal light reflex can be a clinically useful reference marker. The axis formed
by connecting the subject-fixated coaxially sighted corneal light reflex and the
fixation point, the subject-fixated coaxially sighted corneal light reflex axis,
is independent of pupillary dilation and phakic status of the eye. The
relationship of the subject-fixated coaxially sighted corneal light reflex axis
to a refined definition of the visual axis without reference to nodal points, the
foveal-fixation axis, is discussed. The displacement between the subject-fixated
coaxially sighted corneal light reflex and pupil center is described not by an
angle, but by a chord, here termed chord mu. The application of the subject
fixated coaxially sighted corneal light reflex to the surgical centration of
refractive treatments and devices is discussed. CONCLUSION: As a clinically
defined reference marker, the subject-fixated coaxially sighted corneal light
reflex avoids the shortcomings of current ocular axes for clinical application
and may contribute to better consensus in the literature and improved patient
outcomes.
PMID- 25127698
TI - Punctate hyperfluorescence spot as a common choroidopathy of central serous
chorioretinopathy and polypoidal choroidal vasculopathy.
AB - PURPOSE: To characterize punctate hyperfluorescence spot as common choroidopathy
in central serous chorioretinopathy (CSC) and polypoidal choroidal vasculopathy
(PCV). DESIGN: Cross-sectional retrospective study. METHODS: A total of 150
patients with 50 each allocated to CSC, PCV, and typical neovascular age-related
macular degeneration (AMD) groups were included. Punctate hyperfluorescence spot
was determined using mid-to late-phase indocyanine green angiography and
subfoveal choroidal thickness by enhanced depth imaging optical coherence
tomography. Each group was subcategorized based on concurrent punctate
hyperfluorescence spot. RESULTS: The punctate hyperfluorescence spot incidence
was higher in CSC (80.0%) and PCV (86.0%) than in AMD (40.0%, P < .001), with
similar contralateral findings (86.1%, 86.7%, and 60%, respectively, P = .014).
Punctate hyperfluorescence spot lesions comprised clustered polyps connected to
vascular networks mimicking PCV. Choroidal thickness was 370.7 +/- 81.9 MUm,
332.6 +/- 101.6 MUm, and 172.5 +/- 80.1 MUm in affected eyes (P < .001) and 323.0
+/- 70.5 MUm, 306.4 +/- 94.4 MUm, and 180.2 +/- 83.6 MUm in contralateral eyes (P
< .001) in CSC, PCV, and AMD groups, respectively. In the AMD group, choroidal
thickness was greater in eyes with punctate hyperfluorescence spot (204.8 +/-
92.3 MUm) than in those without punctate hyperfluorescence spot (150.2 +/- 62.9
MUm, P = .028) in affected eyes; however, the difference was not observed in
contralateral eyes in the AMD group and in both eyes in the CSC and PCV groups.
CONCLUSIONS: Based on angiography and OCT, punctate hyperfluorescence spot may be
a form of PCV, and CSC and PCV may share common choroidopathy distinct from
typical neovascular AMD. However, infrequent PHS lesions along with thickened
choroids in AMD eyes suggest that AMD may encompass a wide choroidal pathologic
spectrum shared in part with PCV.
PMID- 25127697
TI - Three-dimensional automated choroidal volume assessment on standard spectral
domain optical coherence tomography and correlation with the level of diabetic
macular edema.
AB - PURPOSE: To measure choroidal thickness on spectral-domain optical coherence
tomography (SD OCT) images using automated algorithms and to correlate choroidal
pathology with retinal changes attributable to diabetic macular edema (DME).
DESIGN: Post hoc analysis of multicenter clinical trial baseline data. METHODS:
SD OCT raster scans/fluorescein angiograms were obtained from 284 treatment-naive
eyes of 142 patients with clinically significant DME and from 20 controls. Three
dimensional (3D) SD OCT images were evaluated by a certified independent reading
center analyzing retinal changes associated with diabetic retinopathy. Choroidal
thicknesses were analyzed using a fully automated algorithm. Angiograms were
assessed manually. Multiple endpoint correction according to Bonferroni-Holm was
applied. Main outcome measures were average retinal/choroidal thickness on fovea
centered or peak of edema (thickest point of edema)-centered Early Treatment
Diabetic Retinopathy Study grid, maximum area of leakage, and the correlation
between retinal and choroidal thicknesses. RESULTS: Total choroidal thickness is
significantly reduced in DME (175 +/- 23 MUm; P = .0016) and nonedematous fellow
eyes (177 +/- 20 MUm; P = .009) of patients compared with healthy control eyes
(190 +/- 23 MUm). Retinal/choroidal thickness values showed no significant
correlation (1-mm: P = .27, r(2) = 0.01; 3-mm: P = .96, r(2) < 0.0001; 6-mm: P =
.42, r(2) = 0.006). No significant difference was found in the 1- or 3-mm circle
of a retinal peak of edema-centered grid. All other measurements of
choroidal/retinal thickness (DME vs healthy, DME vs peak of edema-centered, DME
vs fellow, healthy vs fellow, peak of edema-centered vs healthy, peak of edema
centered vs fellow eyes) were compared but no statistically significant
correlation was found. By tendency a thinner choroid correlates with larger
retinal leakage areas. CONCLUSIONS: Automated algorithms can be used to reliably
assess choroidal thickness in eyes with DME. Choroidal thickness was generally
reduced in patients with diabetes if DME is present in 1 eye; however, no
correlation was found between choroidal/retinal pathologies, suggesting different
pathogenetic pathways.
PMID- 25127699
TI - Scleral-fixated capsular tension rings and segments for ectopia lentis in
children.
AB - PURPOSE: To report the short-term outcomes and complications of implantation of
scleral-fixated capsular tension rings and/or capsular tension segments with
intraocular lenses (IOL) in pediatric patients with ectopia lentis. DESIGN:
Retrospective, observational case series. METHODS: Thirteen consecutive pediatric
patients (19 eyes) underwent placement of in-the-bag IOL with either a Cionni
modified capsular tension ring or a capsular tension segment in conjunction with
a conventional capsular tension ring between January 1, 2009 and March 30, 2013
by 3 anterior segment surgeons at a single academic center. The scleral fixation
suture was 9-0 polypropylene in 16 eyes and CV-8 Gore-Tex (expanded
polytetrafluoroethylene) in 3 eyes. Outcome measures included change in corrected
distance visual acuity (CDVA) and complications. RESULTS: The mean age was 10.2
years +/- 4.8 (SD) and the median follow-up, 23.4 months. A Cionni modified
capsular tension ring was implanted in 5 eyes and a capsular tension segment with
an unsutured capsular tension ring was implanted in 12 eyes. In 2 eyes, capsular
tension segment alone was placed. The mean CDVA at the final follow-up (0.10 +/-
0.11 logMAR, 18 eyes) was significantly better than preoperatively (0.58 +/- 0.26
logMAR, 15 eyes) (P < .001). The CDVA at the final follow-up was 20/40 or better
in 18 eyes (94.7%). All IOLs were well centered. Posterior capsule opacification
developed in 11 eyes (57.9%), 9 eyes (47.4%) required neodymium-yttrium-aluminum
garnet capsulotomy, and 3 eyes (15.8%) required pars plana vitrectomy and
posterior capsulotomy. Other complications included broken suture (5.3%) (9-0
polypropylene at CTR eyelet, repaired with CV-8 Gore-Tex), conjunctival
dehiscence (5.3%), suture exposure (5.3%) (trans-scleral 9-0 polypropylene), and
vitreous strand at inferior paracentesis (5.3%). CONCLUSIONS: Implantation of in
the-bag IOL with either a Cionni modified capsular tension ring or a capsular
tension segment in conjunction with a conventional capsular tension ring appears
to be a safe and effective technique for visual rehabilitation in pediatric
ectopia lentis.
PMID- 25127700
TI - Anterior segment optical coherence tomography measurement after neodymium-yttrium
aluminum-garnet laser capsulotomy.
AB - PURPOSE: To evaluate changes in anterior chamber depth (ACD) and angle width
after neodymium-yttrium-aluminum-garnet (Nd:YAG) laser capsulotomy. DESIGN:
Prospective interventional case series. METHODS: In a single institution, 43 eyes
of 43 consecutive pseudophakic patients with symptomatic posterior capsule
opacification (PCO) underwent Nd:YAG laser capsulotomy. Anterior chamber depth
and angle width in pseudophakic eyes with posterior capsule opacification were
measured with anterior segment optical coherence tomography (AS-OCT) before and 3
days after Nd:YAG laser capsulotomy. Preoperative and postoperative measurements
of anterior chamber depth and angle width included the angle opening distance,
measured as the perpendicular distance from the trabecular meshwork at 500 MUm
and 750 MUm anterior to the scleral spur to the anterior iris surface (AOD500 and
AOD750, respectively), and anterior chamber angle (ACA) in the nasal and temporal
quadrants. Main outcome measures were the changes in ACD and angle width
parameters. RESULTS: The mean patient age was 63.4 +/- 3.6 years. Before Nd:YAG
laser capsulotomy, mean ACD, AOD500, AOD750, and ACA (nasal and temporal)
measurements were 3.71 +/- 0.11 mm, 0.61 +/- 0.054 mm, 0.67 +/- 0.063 mm, and
34.5 +/- 1.67 degrees and 34.8 +/- 1.55 degrees, respectively. Three days after
Nd:YAG laser capsulotomy, mean ACD, AOD500, AOD750, and ACA (nasal and temporal)
measurements were 3.77 +/- 0.1 mm, 0.69 +/- 0.06 mm, 0.73 +/- 0.06 mm, and 35.51
+/- 1.64 degrees and 36.17 +/- 1.51 degrees, respectively (P < .01 for all).
CONCLUSIONS: The depth and width of the ACA in pseudophakic eyes with PCO
increased significantly after Nd:YAG laser capsulotomy, as shown by AS-OCT, a
reliable and noncontact method for measuring anterior ocular structures. Our
study shows that the different angle parameters such as ACD, AOD500, AOD750, and
ACA measurements seem highly correlated.
PMID- 25127701
TI - Surgical outcomes of progressive tractional retinal detachment associated with
familial exudative vitreoretinopathy.
AB - PURPOSE: To evaluate various surgeries for treating retinal detachment (RD)
associated with familial exudative vitreoretinopathy (FEVR). DESIGN:
Retrospective, interventional case series. METHODS: The charts of 22 patients who
underwent surgery were reviewed. A complete ophthalmic examination was performed
including wide-field fundus images with fluorescein angiography. The primary and
secondary outcomes were fundus features (vascular activity of the fibrovascular
proliferation and extent of tractional RD) and visual acuity (VA), respectively.
RESULTS: Thirty-one eyes were included (12 eyes underwent scleral buckling, 1
scleral buckling and vitrectomy, 7 vitrectomy alone, and 11 lensectomy and
vitrectomy). Twenty-six eyes were reattached during 1 surgery. Scleral buckling
resulted in cessation of fibrovascular proliferation and retinal reattachment;
only 1 of these eyes required vitrectomy. Lens-sparing vitrectomy resulted in
stabilized fibrovascular proliferation and retinal reattachment. Vitrectomy with
lensectomy did not achieve retinal reattachment in 4 eyes. Fibrovascular
proliferation has a rich vascular component in patients younger than 3 years, and
collagen fibers were present mainly with more advanced age. The postoperative VA
improved in 5 of 8 eyes examined, was unchanged in 1 eye, and decreased in 2 eyes
with macular involvement. CONCLUSIONS: FEVR-induced RDs are highly variable and
require careful preoperative evaluation to determine the best surgical procedure.
Vitrectomy with release of posterior traction is essential in younger patients
with vascularly active fibrovascular proliferation, whereas scleral buckling may
be important for cases with peripheral traction anterior to the equator. In all
cases, peripheral thermal treatment applied to all ischemic areas contributed to
reduced peripheral neovascularization.
PMID- 25127702
TI - [Evaluation of visual performance after implantation of a double C-Loop toric
intraocular lens].
AB - PURPOSE: This study aims to demonstrate the safety and the efficacy of the
Ankoris posterior chamber intraocular lens to correct corneal astigmatism at the
time of cataract surgery. MATERIAL AND METHODS: In this retrospective study, 52
eyes among the first 64 consecutive ones implanted with the Ankoris met the
inclusion criteria. The retrospective analysis of these cases consisted mainly of
the determination of the improvement in visual acuity and postoperative
refraction. The analysis of the astigmatism correction itself was carried out by
the Alpins method. The rotational stability of the implant was analyzed by the
difference between the IOL orientation after one day and 3 months. RESULTS: The
safety index, defined as the postoperative divided by preoperative best visual
acuity, was greater than one in all cases, with a mean of 1.96. The ratio of the
postoperative uncorrected visual acuity with the preoperative best-corrected
acuity was 1.72. The final postoperative astigmatism was -0.40 +/- 0.28 D. The
percentage of astigmatism corrected was 99.3%. The error vector amplitude was 0.1
D with a nearly null orientation. The mean rotation was 2.16 +/- 1.95 degrees .
CONCLUSION: The Ankoris IOL demonstrates, in this relatively large cohort, all
necessary elements to establish that the IOL was able to correct corneal
astigmatism at the same time as cataract surgery.
PMID- 25127703
TI - Ocular tolerability and efficacy of a cationic emulsion in patients with mild to
moderate dry eye disease - a randomised comparative study.
AB - PURPOSE: The purpose of this study was to compare the safety and efficacy of a
new cationic emulsion (CE) with a formulation of polyvinyl alcohol and povidone
(PVA-P) for the treatment of mild to moderate dry eye disease. METHODS: This was
a multicenter, open-label, comparative study. Patients were randomised to receive
CE (Cationorm) or PVA-P (Refresh) (1:1). The following objective criteria were
assessed to compare the two eye drops: tear Break-up Time (TBUT), Schirmer's
test, lissamine green staining (Van Bijsterveld score), corneal fluorescein
staining (Oxford scale) and oculopalpebral examination, on D7 and D28 (end of
study). At these visits, ocular symptoms and safety were also assessed. RESULTS:
Seventy-nine patients were randomised: CE: 44 patients; PVA-P: 35 patients. At
D28, improvement was significantly better for TBUT [CE: 1.7 +/- 2.4 s; PVA-P: 0.6
+/- 1.8 s; P=0.015] and for the Van Bijsterveld score [CE: -1.4 +/- 1.2; PVA-P:
0.9 +/- 1.2; P=0.046] in the CE group. The same applied for the palpebral
erythema score (P=0.023), overall efficacy assessed by the investigators
(P<0.001), and symptoms not related to eye drop instillation (P=0.021).
Improvement was observed from D7. No difference was observed between the two
treatments with regard to ocular safety. CONCLUSION: These results suggest that
in patients with mild to moderate dry eye, Cationorm, in addition to its
moisturizing and lubricating properties, also helps stabilize the tear film due
to its oily component. This study demonstrates the benefit of this new
pharmaceutical form for the treatment of mild to moderate dry eye disease.
PMID- 25127704
TI - Abstinence phenomena of chronic cannabis-addicts prospectively monitored during
controlled inpatient detoxification: cannabis withdrawal syndrome and its
correlation with delta-9-tetrahydrocannabinol and -metabolites in serum.
AB - OBJECTIVE: To investigate the course of cannabis withdrawal syndrome (CWS) within
a controlled inpatient detoxification setting and to correlate severity of CWS
with the serum-levels of delta-9-tetrahydrocannabinol (THC) and its main
metabolites 11-hydroxy-delta-9-tetrahydrocannabinol (THC-OH) and 11-nor-delta-9
tetrahydrocannabinol-9-carboxylic acid (THC-COOH). METHODS: Thirty-nine treatment
seeking chronic cannabis dependents (ICD-10) were studied on admission and on
abstinent days 2, 4, 8 and 16, using a CWS-checklist (MWC) and the Clinical
Global Impression-Severity scale (CGI-S). Simultaneously obtained serum was
analysed to its concentration of THC, THC-OH and THC-COOH. RESULTS: MWC peaked on
day 4 (10.4 +/- 4.6 from 39 points) and declined to 2.9 +/- 2.4 points on day 16.
Women had a significantly stronger CWS than men. The CWS was dominated by
craving>restlessness>nervousness>sleeplessness. CGI-S peaked with 5 out of 7
points. On admission, THC and its metabolites did negatively correlate with the
severity of CWS. There was no significant correlation afterwards, no matter if
CWS was medicated or not. THC-OH in serum declined most rapidly below detection
limit, on median at day 4. At abstinence day 16, the THC-levels of 28.2% of the
patients were still above 1g/ml (range: 1.3 to 6.4 ng/ml). CONCLUSIONS: CWS
increased and then decreased without any correlation between its severity and the
serum-levels of THC or its main metabolites after admission. According to the CGI
S, most patients achieved the condition of 'markedly ill'. Serum THC-OH was most
clearly associated with recent cannabis use. Residual THC was found in the serum
of almost one-third of the patients at abstinence day 16.
PMID- 25127706
TI - Early epileptiform discharges and the yield of prolonged EEG monitoring.
PMID- 25127705
TI - Interactions among drinking identity, gender and decisional balance in predicting
alcohol use and problems among college students.
AB - BACKGROUND: The aim of the present study was to test promising constructs
(decisional balance and drinking identity) and their interaction with gender as
predictors of risky college drinking. We expected that, consistent with previous
work, drinking identity would be positively associated with alcohol consumption
and problems. We further expected that drinking identity would be more strongly
related to outcomes among individuals scoring low in decisional balance.
Additionally, we expect the relationship between drinking identity and alcohol
behavior to vary as a function of decisional balance. METHODS: Participants
included 329 undergraduates (M=23.11; SD=5.63; 74.47% female) who met heavy
drinking criteria (defined as women who consumed 4 or more drinks per occasion
and men who consumed 5 or more drinks per occasion) and completed an online
survey comprised of self-report measures. RESULTS: Decisional balance was
negatively correlated with both drinking and problems, which partially supported
expectations. As expected, drinking identity was positively correlated with
drinking and problems. A two-way interaction emerged between drinking identity
and decisional balance regarding problems, indicating that drinking identity was
associated with more problems, especially among those lower in decisional
balance. A three-way interaction between drinking identity, decisional balance,
and gender emerged regarding problems such that drinking identity was associated
with more problems for those lower in decisional balance and this effect was
stronger among men. DISCUSSION: Findings lend support to the perspective that
decisional balance, drinking identity, and gender are all influential factors
that are associated with the experience of alcohol problems.
PMID- 25127707
TI - Multiscale Lempel-Ziv complexity for EEG measures.
AB - OBJECTIVE: To demonstrate that the classical calculation of Lempel-Ziv complexity
(LZC) has an important limitation when applied to EEGs with rapid rhythms, and to
propose a multiscale approach that overcomes this limitation. METHODS: We have
evaluated, both with simulated and real EEGs, whether LZC calculation neglects
functional characteristics of rapid EEG rhythms. In addition, we have proposed a
procedure to obtain multiple binarization sequences that yield a spectrum of LZC,
and we have explored whether complexity would be better captured using this
computation. RESULTS: In our simulated signals, classical LZC did not capture
modulations of a rapid component when a slower component of more amplitude was
included in the signal. In real EEGs from healthy participants with eyes closed
and eyes open, classical LZC calculation failed to show any difference between
these two conditions. However, a multiscale LZC showed that complexity was lower
for eyes closed than for eyes open conditions. CONCLUSIONS: As hypothesized, our
new approximation captures the complexity of series with fast components masked
by slower rhythms. SIGNIFICANCE: The method we introduce significantly improves
LZC calculation, and it allows a better characterization of complexity of EEG
signals.
PMID- 25127708
TI - Variation in charges for 10 common blood tests in California hospitals: a cross
sectional analysis.
AB - OBJECTIVES: To determine the variation in charges for 10 common blood tests
across California hospitals in 2011, and to analyse the hospital and market-level
factors that may explain any observed variation. DESIGN, SETTING AND
PARTICIPANTS: We conducted a cross-sectional analysis of the degree of charge
variation between hospitals for 10 common blood tests using charge data reported
by all non-federal California hospitals to the California Office of Statewide
Health Planning and Development in 2011. OUTCOME MEASURES: Charges for 10 common
blood tests at California hospitals during 2011. RESULTS: We found that charges
for blood tests varied significantly between California hospitals. For example,
charges for a lipid panel ranged from US$10 to US$10,169, a thousand-fold
difference. Although government hospitals and teaching hospitals were found to
charge significantly less than their counterparts for many blood tests, few other
hospital characteristics and no market-level predictors significantly predicted
charges for blood tests. Our models explained, at most, 21% of the variation
between hospitals in charges for the blood test in question. CONCLUSIONS: These
findings demonstrate the seemingly arbitrary nature of the charge setting
process, making it difficult for patients to act as true consumers in this era of
'consumer-directed healthcare.'
PMID- 25127709
TI - Synergistic loss of prostate cancer cell viability by coinhibition of HDAC and
PARP.
AB - Tumors with BRCA germline mutations are defective in repairing DNA double-strand
breaks (DSB) through homologous recombination (HR) pathways, making them
sensitive to PARP inhibitors (PARPi). However, BRCA germline mutations are rare
in prostate cancer limiting the ability to therapeutically target these pathways.
This study investigates whether histone deacetylase (HDAC) inhibitors (HDACi),
reported to modulate DSB repair pathways in sporadic cancers, can downregulate
DSB repair pathways and sensitize prostate cancer cells to PARPi. Prostate cancer
cells cotreated with the HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA)
and the PARPi, olaparib, demonstrated a synergistic decrease in cell viability
compared with single-agent treatment (combination index < 0.9), whereas normal
prostatic cells did not. Similarly, clonogenicity was significantly decreased
after cotreatment. Flow cytometric cell-cycle analysis and Annexin-V staining
revealed significant apoptosis upon treatment with SAHA+olaparib. This coincided
with increased DNA damage observed by immunofluorescence microscopy analysis of
gammaH2AX foci, a marker of DSBs. In addition, immunoblot analysis showed a
significant and persistent increase in nuclear gammaH2AX levels. Both SAHA and
olaparib downregulated the expression of HR-related proteins, BRCA1 and RAD51,
whereas SAHA + olaparib had an additive effect on RAD51. Silencing RAD51
sensitized prostate cancer cells to SAHA and olaparib alone. Collectively,
cotreatment with HDACi and PARPi downregulated HR-related protein expression and
concomitantly increased DNA damage, resulting in prostate cancer cell death.
IMPLICATIONS: These findings provide a strong rationale for supporting the use of
combined HDAC and PARP inhibition in treating advanced prostate cancer.
PMID- 25127711
TI - EJE Prize 2012: Obesity: from genes to behaviour.
AB - An increase in the consumption of highly palatable foods coupled with a reduction
in the amount of voluntary exercise undertaken has contributed to the rising
prevalence of obesity. However, despite the obvious environmental influences,
there is considerable evidence to support a genetic component to weight gain. In
some people, particularly those who are severely obese, genetic factors play a
major role in the development of their obesity and associated complications.
Studies into the genetic basis of obesity have yielded insights into the
mechanisms involved in the regulation of weight. We now understand that weight is
regulated by neural mechanisms that regulate appetite and energy expenditure and
that disruption of these pathways can result in severe obesity in some patients.
These studies provide a starting point for investigating patients with severe
obesity and may ultimately guide the development of more rational targeted
therapies.
PMID- 25127710
TI - Polymorphisms in the haemagglutinin gene influenced the viral shedding of
pandemic 2009 influenza virus in swine.
AB - Interactions between the viral surface glycoprotein haemagglutinin (HA) and the
corresponding receptors on host cells is one important aspect of influenza virus
infection. Mutations in HA have been described to affect pathogenicity,
antigenicity and the transmission of influenza viruses. Here, we detected
polymorphisms present in HA genes of two pandemic 2009 H1N1 (H1N1pdm09) isolates,
A/California/04/2009 (Ca/09) and A/Mexico/4108/2009 (Mx/09), that resulted in
amino acid changes at positions 186 (S to P) and 194 (L to I) of the mature HA1
protein. Although not reported in the published H1N1pdm09 consensus sequence, the
P186 genotype was more readily detected in primary infected and contact-naive
pigs when inoculated with a heterogeneous mixed stock of Ca/09. Using reverse
genetics, we engineered Ca/09 and Mx/09 genomes by introducing Ca/09 HA with two
naturally occurring variants expressing S186/I194 (HA-S/I) and P186/L194 (HA
P/L), respectively. The Ca/09 HA with the combination of P186/L194 with either
the Ca/09 or Mx/09 backbone resulted in higher and prolonged viral shedding in
naive pigs. This efficiency appeared to be more likely through an advantage in
cell surface attachment rather than replication efficiency. Although these
mutations occurred within the receptor-binding pocket and the Sb antigenic site,
they did not affect serological cross-reactivity. Relative increases of P186 in
publicly available sequences from swine H1N1pdm09 viruses supported the
experimental data, indicating this amino acid substitution conferred an advantage
in swine.
PMID- 25127712
TI - The relationship between glucocorticoid replacement and quality of life in 2737
hypopituitary patients.
AB - OBJECTIVE: Quality of life (QoL) is impaired in hypopituitary patients and
patients with primary adrenal insufficiency. The aim of this study was to analyse
the impact of glucocorticoid (GC) replacement on QoL. The main hypothesis was
that ACTH-insufficient patients experience a dose-dependent deterioration in QoL.
DESIGN, PATIENTS AND METHODS: This was a retrospective analysis of data from KIMS
(Pfizer International Metabolic Database). Data from 2737 adult GH-deficient
(GHD) hypopituitary patients were eligible for analysis. Thirty-six per cent were
ACTH sufficient and 64% ACTH insufficient receiving a mean+/-s.d. hydrocortisone
equivalent (HCeq) dose of 22.3+/-8.7 mg (median 20.0). QoL at baseline and 1 year
after commencement of GH replacement was assessed by the QoL-assessment of GHD in
adults. RESULTS: At baseline, no significant difference in QoL was observed
between ACTH-sufficient and -insufficient patients. Increasing HCeq dose was
associated with worse QoL. Patients on HCeq<=10 mg had the best and patients
receiving >=25 mg demonstrated the poorest QoL. At 1 year of GH replacement, the
improvement in QoL did not differ between ACTH-sufficient and -insufficient
patients, and no association was observed between HCeq dose and QoL improvement.
CONCLUSION: Adult hypopituitary patients with untreated GHD receiving GC
replacement have similar QoL as ACTH-sufficient patients. Among ACTH-insufficient
patients, there is a dose-dependent association between increasing dose and
impaired QoL. This association may be explained by supraphysiological GC exposure
although it remains plausible that clinicians may have increased GC doses in
order to address otherwise unexplained QoL deficits.
PMID- 25127713
TI - Human epididymis protein 4 (HE4) in laboratory medicine and an algorithm in renal
disorders.
AB - Over the past three decades, cancer antigen (CA) 125 has been utilized for
monitoring women who were treated for ovarian cancer. However, this tumor marker
showed several limitations such as false elevation in benign pelvic diseases and,
in turn, no alterations in ovarian tumors at early stages with a relatively high
ratio. For more than ten years, the human epididymis protein 4 (HE4) has become
available for the routine laboratory repertoire, showing a higher sensitivity and
specificity compared to that of CA125 in ovarian malignancies, but also in other
types of tumors based on recently accumulated clinical data. Despite its
remarkable diagnostic characteristics, in certain cases, the evaluation of HE4
results may be problematic when patients suffer from additional conditions that
may alter HE4 level. Besides the direct effects of age and smoking, menopause
status and decreased renal function also show a substantial impact on HE4 values,
which should be considered in each patient. For this purpose, we attempted to
create a new formula and an algorithm that may be helpful to predict the
probability of the presence of ovarian tumor by using the concentrations of HE4
and CA125.
PMID- 25127714
TI - A qualitative synthesis of diabetes self-management strategies for long term
medical outcomes and quality of life in the UK.
AB - BACKGROUND: Qualitative research on self-management for people with Type 2
Diabetes Mellitus (T2DM) has typically reported one-off retrospective accounts of
individuals' strategies. The aim of this research was to identify the ways in
which self-management strategies are perceived by people with T2DM as being
either supportive or unsupportive over time, by using qualitative findings from
both longitudinal intervention studies and usual care. METHODS: A systematic
review of qualitative literature, published between 2000 and 2013, was conducted
using a range of searching techniques. 1374 prospective qualitative papers
describing patients' experiences of self-management strategies for T2DM were
identified and screened. Of the 98 papers describing qualitative research
conducted in the UK, we identified 4 longitudinal studies (3 intervention
studies, 1 study of usual care). Key concepts and themes were extracted, reviewed
and synthesised using meta-ethnography techniques. RESULTS: Aspects of self
management strategies in clinical trials (e.g. supported exercise regimens) can
be perceived as enabling the control of biomarkers and facilitative of quality of
life. In contrast, aspects of self-management strategies outwith trial conditions
(e.g. self-monitoring) can be perceived of as negative influences on quality of
life. For self-management strategies to be sustainable in the long term, patients
require a sense of having a stake in their management that is appropriate for
their beliefs and perceptions, timely information and support, and an overall
sense of empowerment in managing their diabetes in relation to other aspects of
their life. This enables participants to develop flexible diabetes management
strategies that facilitate quality of life and long term medical outcomes.
CONCLUSIONS: This synthesis has explored how patients give meaning to the
experiences of interventions for T2DM and subsequent attempts to balance
biomarkers with quality of life in the long term. People with T2DM both construct
and draw upon causal accounts as a resource, and a means to counter their
inability to balance medical outcomes and quality of life. These accounts can be
mediated by the provision of timely and tailored information and support over
time, which can allow people to develop a flexible regimen that can facilitate
both quality of life and medical outcomes.
PMID- 25127715
TI - Comparison of single and two-tunnel techniques during open treatment of
acromioclavicular joint disruption.
AB - BACKGROUND: Coracoclavicular (CC) ligament reconstruction with semitendinosus
tendon (ST) grafts has become more popular and has achieved relatively good
results; however optimal reconstruction technique, single-tunnel or two-tunnel,
still remains controversial. This paper is to compare the clinical and
radiographic data of allogenous ST grafting with single- or two-tunnel
reconstruction techniques of the AC joint. METHODS: The outcomes of 21
consecutive patients who underwent anatomical reduction and ST grafting for AC
joint separation were reviewed retrospectively. Patients were divided into two
groups: single-tunnel group (11) and two-tunnel group (10). All patients were
evaluated clinically and radiographically using a modified UCLA rating scale.
RESULTS: The majority of separations (18 of 21) were Rockwood type V, with one
each in type III, IV and VI categories. The overall mean follow-up time was 16
months, and at the time of the latest follow-up, the overall mean UCLA rating
score was 14.1 (range 8-20).The percentage of good-to-excellent outcomes was
significantly higher for patients with the two-tunnel technique than for those
with the one-tunnel technique (70% vs. 18%, respectively, p = 0.03). Within the
single-tunnel group, there was no statistically significant difference in
percentage of good-to-excellent outcomes between patients with vs. without
tightrope augmentation (17% vs 20%, p > 0.99). Similarly, within the two-tunnel
group, there was no significant difference in the percentage of good-to-excellent
outcomes between the graft only and augment groups (67% vs. 75%, p > 0.99).
CONCLUSION: Anatomical reduction of the AC joint and reconstruction CC ligaments
are crucial for optimal joint stability and function. Two-tunnel CC
reconstruction with an allogenous ST graft provides superior significantly better
radiographic and clinical results compared to the single-tunnel reconstruction
technique.
PMID- 25127716
TI - Involvement of the chemokine CCL3 and the purinoceptor P2X7 in the spinal cord in
paclitaxel-induced mechanical allodynia.
AB - BACKGROUND: Paclitaxel is an effective chemotherapeutic agent widely used for the
treatment of solid tumors. The major dose-limiting toxicity of paclitaxel is
peripheral neuropathy. The mechanisms underlying the development and maintenance
of paclitaxel-induced peripheral neuropathy are still unclear, and there are no
currently established effective treatments. Accumulating evidence in models of
neuropathic pain in which peripheral nerves are lesioned has implicated spinal
microglia and chemokines in pain hypersensitivity, but little is know about their
roles in chemotherapy-induced peripheral neuropathy. In the present study, we
investigated the role of CC-chemokine ligand 3 (CCL3) in the spinal cord in the
development and maintenance of mechanical allodynia using a rat model of
paclitaxel-induced neuropathy. FINDINGS: Repeated intravenous administration of
paclitaxel induced a marked decrease in paw withdrawal threshold in response to
mechanical stimulation (mechanical allodynia). In these rats, the number of
microglia in the spinal dorsal horn (SDH) was significantly increased. Paclitaxel
treated rats showed a significant increase in the expression of mRNAs for CCL3
and its receptor CCR5 in the SDH. Intrathecal administration of a CCL3
neutralizing antibody not only attenuated the development of paclitaxel-induced
mechanical allodynia but also reversed its maintenance. Paclitaxel also
upregulated expression of purinoceptor P2X7 receptors (P2X7Rs), which have been
implicated in the release of CCL3 from microglia, in the SDH. The selective P2X7R
antagonist A438079 had preventive and reversal effects on paclitaxel-induced
allodynia. CONCLUSIONS: Our findings suggest a contribution of CCL3 and P2X7Rs in
the SDH to paclitaxel-induced allodynia and may provide new therapeutic targets
for paclitaxel-induced painful neuropathy.
PMID- 25127717
TI - The efficacy-effectiveness distinction in trials of alcohol brief intervention.
AB - Three recent sets of null findings from trials of alcohol brief intervention (BI)
have been disappointing to those who wish to see a reduction in alcohol-related
harm through the widespread dissemination of BI. Saitz (7) has suggested that
these null findings result from a failure to translate the effects of BI seen in
efficacy trials, which are thought to contribute mainly to the beneficial effects
of BI shown in meta-analyses, to effectiveness trials conducted in real-world
clinical practice. The present article aims to: (i) clarify the meaning of the
terms "efficacy" and "effectiveness" and other related concepts; (ii) review the
method and findings on efficacy-effectiveness measurement in the 2007 Cochrane
Review by Kaner and colleagues; and (iii) make suggestions for further research
in this area. Conclusions are: 1) to avoid further confusion, terms such as
"efficacy trial", "effectiveness trial", "clinical representativeness", etc.
should be clearly defined and carefully used; 2) applications of BI to novel
settings should begin with foundational research and developmental studies,
followed by efficacy trials, and political pressures for quick results from
premature effectiveness trials should be resisted; 3) clear criteria are
available in the literature to guide progress from efficacy research, through
effectiveness research, to dissemination in practice; 4) to properly interpret
null findings from effectiveness studies, it is necessary to ensure that
interventions are delivered as intended; 5) in future meta-analyses of alcohol BI
trials, more attention should be paid to the development and application of a
psychometrically robust scale to measure efficacy-effectiveness or clinical
representativeness; 6) the null findings under consideration cannot be firmly
attributed to a failure to translate effects from efficacy trials to real-world
practice, because it is possible that the majority of trials included in meta
analyses on which the evidence for the beneficial effects of alcohol BI was based
tended to be effectiveness rather than efficacy trials; and 7) a hypothesis to
explain the null findings in question is that they are due to lack of fidelity in
the implementation of BI in large, organizationally complex, cluster randomized
trials.
PMID- 25127718
TI - Annona muricata leaves induced apoptosis in A549 cells through mitochondrial
mediated pathway and involvement of NF-kappaB.
AB - BACKGROUND: Annona muricata leaves have been reported to have antiproliferative
effects against various cancer cell lines. However, the detailed mechanism has
yet to be defined. The current study was designed to evaluate the molecular
mechanisms of A. muricata leaves ethyl acetate extract (AMEAE) against lung
cancer A549 cells. METHODS: The effect of AMEAE on cell proliferation of
different cell lines was analyzed by MTT assay. High content screening (HCS) was
applied to investigate the suppression of NF-kappaB translocation, cell membrane
permeability, mitochondrial membrane potential (MMP) and cytochrome c
translocation from mitochondria to cytosol. Reactive oxygen species (ROS)
formation, lactate dehydrogenase (LDH) release and activation of caspase-3/7, -8
and -9 were measured while treatment. The western blot analysis also carried out
to determine the protein expression of cleaved caspase-3 and -9. Flow cytometry
analysis was used to determine the cell cycle distribution and phosphatidylserine
externalization. Quantitative PCR analysis was performed to measure the gene
expression of Bax and Bcl-2 proteins. RESULTS: Cell viability analysis revealed
the selective cytotoxic effect of AMEAE towards lung cancer cells, A549, with an
IC50 value of 5.09 +/- 0.41 MUg/mL after 72 h of treatment. Significant LDH
leakage and phosphatidylserine externalization were observed in AMEAE treated
cells by fluorescence analysis. Treatment of A549 cells with AMEAE significantly
elevated ROS formation, followed by attenuation of MMP via upregulation of Bax
and downregulation of Bcl-2, accompanied by cytochrome c release to the cytosol.
The incubation of A549 cells with superoxide dismutase and catalase significantly
attenuated the cytotoxicity caused by AMEAE, indicating that intracellular ROS
plays a pivotal role in cell death. The released cytochrome c triggered the
activation of caspase-9 followed by caspase-3. In addition, AMEAE-induced
apoptosis was accompanied by cell cycle arrest at G0/G1 phase. Moreover, AMEAE
suppressed the induced translocation of NF-kappaB from cytoplasm to nucleus.
CONCLUSIONS: Our data showed for the first time that the ethyl acetate extract of
Annona muricata inhibited the proliferation of A549 cells, leading to cell cycle
arrest and programmed cell death through activation of the mitochondrial-mediated
signaling pathway with the involvement of the NF-kB signalling pathway.
PMID- 25127719
TI - Particle beam radiation therapy using carbon ions and protons for oligometastatic
lung tumors.
AB - BACKGROUND: A study was undertaken to analyze the efficacy and feasibility of
particle beam radiation therapy (PBRT) using carbon ions and protons for the
treatment of patients with oligometastatic lung tumors. METHODS: A total of 47
patients with 59 lesions who underwent PBRT for oligometastatic lung tumors
between 2003 and 2011 were included in this study. Patient median age was 66
(range, 39-84) years. The primary tumor site was the colorectum in 11 patients
(23.4%), lung in 10 patients (21.3%) and a variety of other sites in 26 patients
(55.3%). Thirty-one patients (66%) received chemotherapy prior to PBRT. Thirty
three lesions were treated with 320-MeV carbon ions and 26 were treated with 150-
or 210-Mev protons in 1-4 portals. A median total dose of 60 (range, 52.8-70.2)
GyE was delivered at the isocenter in 8 (range, 4-26) fractions. RESULTS: The
median follow-up time was 17 months. The local control, overall survival and
progression-free survival rates at 2 years were 79%, 54 and 27% respectively.
PBRT-related toxicities were observed; six patients (13%) had grade 2 toxicity
(including grade 2 radiation pneumonitis in 2) and six patients (13%) had grade 3
toxicity. Univariate analysis indicated that patients treated with a biologically
equivalent dose of 10 (BED10) <110 GyE10, had a significantly higher local
recurrence rate. Local control rates were relatively lower in the subsets of
patients with the colorectum as the primary tumor site. No local progression was
observed in metastases from colorectal cancer irradiated with a BED10 >= 110
GyE10. There was no difference in treatment results between proton and carbon ion
therapy. CONCLUSIONS: PRBT is well tolerated and effective in the treatment of
oligometastatic lung tumors. To further improve local control, high-dose PBRT
with a BED10 >= 110 GyE10 may be promising. Further investigation of PBRT for
lung oligometastases is warranted.
PMID- 25127720
TI - The Namaqua rock mouse (Micaelamys namaquensis) as a potential reservoir and host
of arthropod vectors of diseases of medical and veterinary importance in South
Africa.
AB - BACKGROUND: The role of endemic murid rodents as hosts of arthropod vectors of
diseases of medical and veterinary significance is well established in the
northern hemisphere. In contrast, endemic murids are comparatively understudied
as vector hosts in Africa, particularly in South Africa. Considering the great
rodent diversity in South Africa, many of which may occur as human commensals,
this is unwarranted. METHODS: In the current study we assessed the ectoparasite
community of a widespread southern African endemic, the Namaqua rock mouse
(Micaelamys namaquensis), that is known to carry Bartonella spp. and may attain
pest status. We aimed to identify possible vectors of medical and/or veterinary
importance which this species may harbour and explore the contributions of
habitat type, season, host sex and body size on ectoparasite prevalence and
abundance. RESULTS: Small mammal abundance was substantially lower in grasslands
compared to rocky outcrops. Although the small mammal community comprised of
different species in the two habitats, M. namaquensis was the most abundant
species in both habitat types. From these 23 ectoparasite species from four taxa
(fleas, ticks, mites and lice) were collected. However, only one flea (Xenopsylla
brasiliensis) and one tick species (Haemaphysalis elliptica) have a high zoonotic
potential and have been implicated as vectors for Yersinia pestis and Bartonella
spp. and Rickettsia conorii, respectively. The disease status of the most
commonly collected tick (Rhipicephalus distinctus) is currently unknown. Only
flea burdens differed markedly between habitat types and increased with body
size. With the exception of lice, all parasite taxa exhibited seasonal peaks in
abundance during spring and summer. CONCLUSION: M. namaquensis is the dominant
small mammal species irrespective of habitat type. Despite the great ectoparasite
diversity harboured by M. namaquensis, only a small number of these are known as
vectors of diseases of medical and/or veterinary importance but occur at high
prevalence and/or abundance. This raises concern regarding the potential of this
host as an endemic reservoir for zoonotic diseases. Consequently, additional
sampling throughout its distributional range and research addressing the role of
M. namaquensis as a reservoir for zoonotic diseases in southern Africa is
urgently needed.
PMID- 25127721
TI - Visualization of the physical and functional interaction between hMYH and hRad9
by Dronpa bimolecular fluorescence complementation.
AB - BACKGROUND: Human MutY glycosylase homolog (hMYH), a component of the base
excision repair pathway, is responsible for the generation of
apurinic/apyrimidinic sites. Rad9-Rad1-Hus1 (9-1-1) is a heterotrimeric protein
complex that plays a role in cell cycle checkpoint control and DNA repair. In
humans, hMYH and 9-1-1 interact through Hus1 and to a lesser degree with Rad1 in
the presence of DNA damage. In Saccharomyces pombe, each component of the 9-1-1
complex interacts directly with SpMYH. The glycosylase activity of hMYH is
stimulated by Hus1 and the 9-1-1 complex and enhanced by DNA damage treatment.
Cells respond to different stress conditions in different manners. Therefore, we
investigated whether Rad9 interacted with hMYH under different stresses. Here, we
identified and visualized the interaction between hRad9 and hMYH and investigated
the functional consequences of this interaction. RESULTS: Co-IP and BiFC
indicates that hMYH interacts with hRad9. As shown by GST-pull down assay, this
interaction is direct. Furthermore, BiFC with deletion mutants of hMYH showed
that hRad9 interacts with N-terminal region of hMYH. The interaction was enhanced
by hydroxyurea (HU) treatment. mRNA and protein levels of hMYH and hRad9 were
increased following HU treatment. A marked increase in p-Chk1 (S345) and p-Cdk2
(T14, Y15) was observed. But this phosphorylation decreased in siMYH- or siRad9
transfected cells, and more pronounced decrease observed in co-transfected cells.
CONCLUSIONS: Our data reveal that hRad9 interacts directly with N-terminal region
of hMYH. This interaction is enhanced by HU treatment. Knockdown of one or both
protein result in decreasing Chk1 and Cdk2 phosphorylation. Since both protein
functions in the early detection of DNA damage, we suggest that this interaction
occurs early in DNA damage pathway.
PMID- 25127722
TI - Assessment of retention force and bone apposition in two differently coated
femoral stems after 6 months of loading in a goat model.
AB - BACKGROUND: Since the introduction of uncemented hip implants, there has been a
search for the best surface coating to enhance bone apposition in order to
improve retention. The surface coating of the different stems varies between
products. The aim was to assess the retention force and bone adaption in two
differently coated stems in a weight-bearing goat model. MATERIALS AND METHODS:
Hydroxyapatite (HA) and electrochemically deposited calcium phosphate (CP; Bonit)
on geometrically comparable titanium-based femoral stems were implanted into 12
(CP group) and 35 (HA group) goats. The animal model included physiological
loading of the implants for 6 months. The pull-out force of the stems was
measured, and bone apposition was microscopically evaluated. RESULTS: After
exclusion criteria were applied, the number of available goats was 4 in the CP
group and 11 in the HA group. The CP-coated stems had significantly lower
retention forces compared with the HA-coated ones after 6 months (CP median 47 N,
HA median 1,696 N, p = 0.003). Bone sections revealed a lower degree of bone
apposition in the CP-coated stems, with more connective tissue in the
bone/implant interface compared with the HA group. CONCLUSION: In this study, HA
had better bone apposition and needed greater pull-out force in loaded implants.
The application of CP on the loaded titanium surface to enhance the apposition of
bone is questioned.
PMID- 25127723
TI - Proximal and distal determinants of stressful work: framework and analysis of
retrospective European data.
AB - BACKGROUND: While robust evidence on associations of stressful work with health
exists, less research is available on determinants of stressful work in terms of
respondents' characteristics (proximal factors) and in terms of national labour
market policies (distal factors). In this article we analyse proximal (childhood
circumstances and labour market disadvantage) and distal determinants (national
compensation and integration policies) of stressful work in a comprehensive
framework. METHODS: We use data from the third wave of the Survey of Health,
Ageing and Retirement in Europe (SHARE), with retrospective information on
individual life courses collected among 11181 retired men and women in 13
European countries (2008-2009). To test our hypotheses we estimate multilevel
regression models. RESULTS: Results show that stressful work is related to
disadvantaged circumstances during childhood. To some extent this association is
explained by labour market disadvantage during adulthood. Additionally, well
developed labour market integration policies are related to lower overall levels
of stressful work at national level. CONCLUSION: This analysis provides first
evidence of important determinants of stressful work, both in terms of pre
employment conditions (childhood circumstances) and in terms of contextual macro
social policies.
PMID- 25127724
TI - miRNA expression profiles in cerebrospinal fluid and blood of patients with acute
ischemic stroke.
AB - The aims of the study were (1) to determine whether miRNAs (microRNAs) can be
detected in the cerebrospinal fluid (CSF) and blood of patients with ischemic
stroke and (2) to compare these miRNA profiles with corresponding profiles from
other neurological patients to address whether the miRNA profiles of CSF or blood
have potential usefulness as diagnostic biomarkers of ischemic stroke. CSF from
patients with acute ischemic stroke (n = 10) and patients with other neurological
diseases (n = 10) was collected by lumbar puncture. Blood samples were taken
immediately after. Expression profiles in the cell-free fractions of CSF and
blood were analyzed by a microarray technique (miRCURY LNATM microRNA Array,
Exiqon A/S, Denmark) using a quantitative PCR (qPCR) platform containing 378
miRNA primers. In total, 183 different miRNAs were detected in the CSF, of which
two miRNAs (let-7c and miR-221-3p) were found upregulated in relation to stroke.
In the blood, 287 different miRNAs were detected of which two miRNAs (miR-151a-3p
and miR-140-5p) were found upregulated and one miRNA (miR-18b-5p) was found
downregulated in the stroke group. Some miRNAs occurred exclusively in the CSF
including miR-523-3p which was detected in 50 % of the stroke patients, whereas
it was completely absent in controls. Our preliminary results demonstrate that it
is possible to detect and profile miRNAs in CSF and blood from patients with
neurological diseases. Some miRNAs appear differentially expressed in the CSF and
others in the blood of stroke patients. Currently, we are validating our results
in larger groups of patients.
PMID- 25127726
TI - Mass effect from hepatomegaly in polycystic kidney disease.
PMID- 25127727
TI - Capsule commentary on Larochelle et al., Reducing excess biomarker testing at an
academic medical center.
PMID- 25127725
TI - Intensive blood pressure control, falls, and fractures in patients with type 2
diabetes: the ACCORD trial.
AB - BACKGROUND: There are few rigorous studies to confirm or refute the commonly
cited concern that control of blood pressure to lower thresholds may result in an
increased risk of falls and fractures. OBJECTIVE: To compare falls and fractures
in participants with type 2 diabetes in the intensive (targeting a systolic blood
pressure of < 120 mmHg) and standard (targeting a systolic blood pressure of <
140 mmHg) blood pressure control arms of the Action to Control Cardiovascular
Risk in Diabetes (ACCORD) randomized trial (N = 4,733). PARTICIPANTS: A subset of
3,099 participants self-reported annually on the occurrence of falls and non
spine fractures. Fractures were centrally adjudicated. MAIN MEASURES: The
incidence of falls in the two treatment groups was compared using a random
effects negative binomial model, and fracture risk was compared using Cox
proportional hazards models. KEY RESULTS: At enrollment in both groups, the mean
age was 62 years, 44% were women, 25% were Black, and mean blood pressure was
138/75 mmHg. During follow-up, all classes of medications, particularly thiazide
diuretics, were more commonly prescribed in the intensive group. After 1 year of
follow-up, the mean systolic blood pressure was 133 +/- 15 mmHg in the standard
group and 119 +/- 14 mmHg in the intensive group. The adjusted rate of falls did
not differ in the intensive and standard groups (62.2/100 person-years vs.
74.1/100 person-years, RR = 0.84, 95% CI 0.54-1.29, p = 0.43). The risk of non
spine fractures was nonsignificantly lower in the intensive than in the standard
blood pressure group (HR 0.79, 95% CI 0.62-1.01, p = 0.06). CONCLUSIONS: We
conclude that intensive antihypertensive treatment that lowered mean systolic
blood pressure to below 120 mmHg was not associated with an increased risk of
falls or non-spine fractures in patients age 40 to 79 years with type 2 diabetes.
PMID- 25127729
TI - Capsule commentary on Marc et al., Reliability and validity of the Haitian Creole
PHQ-9.
PMID- 25127728
TI - Geographic and racial/ethnic variations in patterns of multimorbidity burden in
patients with type 2 diabetes.
AB - BACKGROUND: Multimorbidity presents a significant public health challenge, but
regional, rural/urban, and racial/ethnic differences in patterns of
multimorbidity in diabetes are poorly understood. OBJECTIVE: To describe patterns
of multimorbidity in medical and mental health by regional, rural/urban, and
racial/ethnic variation in patients with type 2 diabetes mellitus. DESIGN:
Retrospective cohort study from 2002 through 2006 PARTICIPANTS: A national cohort
of 892,223 veterans with diabetes MAIN MEASURES: Multimorbidity was the main
outcome defined as: the measure of multimorbidity and two categorical outcomes,
with pattern of medical and mental health comorbidities combined and separately.
KEY RESULTS: Among patients, 52% had 2+ comorbidities, 33% had a single
comorbidity, and 14% had no comorbidity; 13.9% had both medical and mental health
comorbidities, 70.3% had medical only, and 1.5% had mental health only. The odds
of having 3+ comorbidities were nearly fourfold greater in patients 75 years and
older relative to patients younger than 50 years (OR=3.95 [95% CI: 3.84, 4.06]).
Compared to non-Hispanic whites, the odds of 3+ comorbidities among non-Hispanic
blacks were 1.67 times greater (95% CI: 1.63, 1.71). Hispanics were more likely
to have a mental health comorbidity alone (OR=1.20 [95% CI: 1.13, 1.28]) than non
Hispanic whites. For patients living in rural areas, the odds were higher of
having 3+ comorbidities (OR=1.21 [95% CI: 1.19, 1.23]) and of having both medical
and mental health comorbidities (OR=1.15 [95% CI: 1.13, 1.17]) compared to urban
dwellers. CONCLUSIONS: Among individuals with diabetes, traditionally
disadvantaged groups, including non-Hispanic blacks and rural patients, appear to
bear the greatest burden and risk of multimorbidity. Significantly greater odds
with increasing number of comorbidities were seen by race/ethnicity, rural
residence, and geographic region.
PMID- 25127730
TI - Tackling disparities in influenza vaccination in primary care: it takes a team.
PMID- 25127732
TI - Osteometric analysis for sexing of modern sternum - an autopsy study from South
India.
AB - Estimation of sex is considered as one of the essential parameters in forensic
anthropology and requires foremost attention in the analysis of commingled and
unidentified remains. In India, there is a paucity of population specific
morphometric standards for identifying sex from unknown human remains in
different population groups. The present research is an osteometric analysis to
study the sexual dimorphism of the sternum of South Indian origin using
statistical considerations. The study sample constituted of adult autopsied
sternums of known age and sex. Five linear measurements (length of the manubrium,
mesosternum, manubrium and mesosternum together, and width at 1st and at 3rd
sternebra) were examined during the study. Three indices (manubrio-corpus Index,
ratio of the length of the mesosternum and manubrium, and sternubrial-width
index) were computed from the length and width measurements of the sternum.
Statistical analysis was done using SPSS computer software and Student's t-test
was applied to find the sex differences in these variables. While statistically
significant sex differences were observed for all the five linear measurements of
the sternum, none of the sternal indices showed statistically significant sex
differences. Discriminant function and logistic regression analysis were
performed to derive the predicting models for estimation of sex from the
different variables. The predictability of sternal measurements in sexing using
univariate models ranged between 67.5% for the width at 3rd sternebra and 74.4%
for the combined length of manubrium and mesosternum. The classification accuracy
rates of sternal measurements were observed to be higher when multivariate
analysis was performed. Length of manubrium and mesosternum together along with
width at 1st sternebra yielded maximum accuracy of 79.5% (discriminant function
analysis) and 81.2% (logistic regression analysis) in sexing of male and female
sternum. The present research concludes that the application of sternum in sex
estimation should be restricted to cases when other more reliable bones for
sexing are not available to the investigators.
PMID- 25127733
TI - Synthesis and characterization of antifouling poly(N-acryloylaminoethoxyethanol)
with ultralow protein adsorption and cell attachment.
AB - Rational design of effective antifouling polymers is challenging but important
for many fundamental and applied applications. Herein we synthesize and
characterize an N-acryloylaminoethoxyethanol (AAEE) monomer, which integrates
three hydrophilic groups of hydroxyl, amide, and ethylene glycol in the same
material. AAEE monomers were further grafted and polymerized on gold substrates
to form polyAAEE brushes with well-controlled thickness via surface-initiated
atomic transfer radical polymerization (SI-ATRP), with particular attention to a
better understanding of the molecular structure-antifouling property relationship
of hydroxyl-acrylic-based polymers. The surface hydrophilicity and antifouling
properties of polyAAEE brushes as a function of film thickness are studied by
combined experimental and computational methods including surface plasmon
resonance (SPR) sensors, atomic force microscopy (AFM), cell adhesion assay, and
molecular dynamics (MD) simulations. With the optimal polymer film thicknesses
(~10-40 nm), polyAAEE-grafted surfaces can effectively resist protein adsorption
from single-protein solutions and undiluted human blood plasma and serum to a
nonfouling level (i.e., <0.3 ng/cm(2)). The polyAAEE brushes also highly resist
mammalian cell attachment up to 3 days. MD simulations confirm that the
integration of three hydrophilic groups induce a stronger and closer hydration
layer around polyAAEE, revealing a positive relationship between surface
hydration and antifouling properties. The molecular structure-antifouling
properties relationship of a series of hydroxyl-acrylic-based polymers is also
discussed. This work hopefully provides a promising structural motif for the
design of new effective antifouling materials beyond traditional ethylene glycol
based antifouling materials.
PMID- 25127731
TI - Interest in genetic testing in Ashkenazi Jewish Parkinson's disease patients and
their unaffected relatives.
AB - Our objective was to explore interest in genetic testing among Ashkenazi Jewish
(AJ) Parkinson's Disease (PD) cases and first-degree relatives, as genetic
testing for LRRK2 G2019S is widely available. Approximately 18 % of AJ PD cases
carry G2019S mutations; penetrance estimations vary between 24 and 100 % by age
80. A Genetic Attitude Questionnaire (GAQ) was administered at two New York sites
to PD families unaware of LRRK2 G2019S mutation status. The association of
G2019S, age, education, gender and family history of PD with desire for genetic
testing (outcome) was modeled using logistic regression. One-hundred eleven PD
cases and 77 relatives completed the GAQ. Both PD cases and relatives had
excellent PD-specific genetic knowledge. Among PD, 32.6 % "definitely" and 41.1 %
"probably" wanted testing, if offered "now." Among relatives, 23.6 % "definitely"
and 36.1 % "probably" wanted testing "now." Desire for testing in relatives
increased incrementally based on hypothetical risk of PD. The most important
reasons for testing in probands and relatives were: if it influenced medication
response, identifying no mutation, and early prevention and treatment. In
logistic regression, older age was associated with less desire for testing in
probands OR = 0.921 95%CI 0.868-0.977, p = 0.009. Both probands and relatives
express interest in genetic testing, despite no link to current treatment or
prevention.
PMID- 25127734
TI - Re-description of a genetically typed, single oocyst line of the turkey
coccidium, Eimeria adenoeides Moore and Brown, 1951.
AB - The Guelph strain of Eimeria adenoeides was obtained from a commercial turkey
flock in Ontario, Canada, in 1985. Single oocyst derived lines of E. adenoeides
were propagated, and one of them used to re-describe biological and morphological
features of E. adenoeides in the turkey. Oocysts of this strain are within the
lower size ranges in the original species description reported by Moore and Brown
(1951); oocysts of the Guelph strain averaged 18.7 +/- 1.4 MUm (16.7-22.5) by
14.3 +/- 0.9 MUm (13-16.2, n = 30) with a shape index (SI) of 1.3 +/- 0.1. It is
possible that the original species description was based, at least in part, on a
mixed culture of two or more Eimeria species. Immature first-generation meronts
of E. adenoeides Guelph strain were observed histologically at 32 h post
infection in the ileum and cecal neck. Early studies reported only two asexual
generations suggested that first asexual cycle observed at 32 h post-infection
was overlooked. In the present study, three asexual generations were observed
before the start of gametogony. The Guelph strain is also characterized by a
prepatent period of 112 h. The Guelph strain of E. adenoeides is a highly
pathogenic coccidium that forms classic cecal lesions, including prominent
caseous cecal cores, during moderate to severe infections. The maximum output of
oocysts (1.77 * 10(7) per bird) was obtained from birds inoculated with 1 * 10(3)
oocysts; maximum fecundity (1.55 * 10(5) oocyst shed per oocyst inoculated) was
obtained with an inoculation of 1 * 10(2) oocysts, but fecundity dropped
dramatically as the inoculation dose increased. To promote stability of the E.
adenoeides species concept, neotype specimens (a parahapantotype slides series
and phototype) have been designated and deposited for future reference.
PMID- 25127735
TI - Influence of environmental factors on Argulus japonicus occurrence of Guangdong
province, China.
AB - To assess the effects of abiotic factors on Argulus japonicus occurrence in
freshwater ecosystem, we sampled fish, free-swimming parasites, and submerged
objects from rivers, fish farms, and ponds (reservoirs and lakes) at 27 locations
in Guangdong province, China, from July, 2010, to March, 2013. Friedman's test
and Spearman's correlation coefficient (r) were used to investigate relationship
between A. japonicus occurrence and abiotic factors in three aquatic systems.
Correlation of monthly density, mean density, prevalence, abundance, and
intensity of A. japonicus with water temperature, biochemical oxygen demand of 5
days, chemical oxygen demand, and ammonia were very significant, but negative
relation with pH, dissolved oxygen, and total phosphorus components.
Nevertheless, total nitrogen components showed an insignificant impact on A.
japonicus incidence. In addition, water temperature and stability were two key
factors controlling A. japonicus infestation. Our study revealed the capability
of A. japonicus to inhabit and prevail in heavily polluted freshwater. Results
demonstrate that A. japonicus has good adaptability to the environmental factors'
stress but cannot be used as a biological indicator of environmental pollution.
PMID- 25127737
TI - An analysis of historical Mussel Watch Programme data from the west coast of the
Cape Peninsula, Cape Town.
AB - The concentrations of metals in the mussel Mytilus galloprovincialis (Lamarck,
1819) prevalent along the west coast of the Cape Peninsula, Cape Town are
presented. The mussels were sampled during the routine "Mussel Watch Programme"
(MWP) between 1985 and 2008. Levels of Cu, Cd, Pb, Zn, Hg, Fe and Mn at Cape
Point, Hout Bay, Sea Point, Milnerton and Bloubergstrand were analysed for autumn
and spring and showed consistent similar mean values for the five sites. There
was a highly significant temporal (annual and seasonal) difference between all
metals as well as a significant difference in metal concentrations between the
five sites. The concentrations of Zn, Fe, Cd and Pb were higher than previous
investigations and possibly indicative of anthropogenic sources of metals. The
results provide a strong motivation to increase efforts in marine pollution
research in the area.
PMID- 25127736
TI - Identity of rumen fluke in deer.
AB - As evidence is growing that in many temperate areas paramphistome infections are
becoming more common and widespread, this study was undertaken to determine the
role of deer as reservoirs for rumen fluke infections in livestock. A total of
144 deer faecal samples (88 from fallow deer, 32 from red deer and 24 samples
from sika, sika/red deer hybrids) were screened for the presence of fluke eggs.
Based on the ITS-2 rDNA locus plus flanking 5.8S and 28S sequences (ITS-2+),
fluke eggs were identified to species level. Our results indicate that, of the 3
deer species, fallow deer had the highest fluke infection rates. Two rumen fluke
species, Calicophoron daubneyi and Paramphistomum leydeni, with morphologically
distinct eggs, were identified. Concurrent infections of the two paramphistome
species and liver fluke, Fasciola hepatica, were common. Considering the
comparatively low egg burdens observed in this study, it is unlikely that deer
represent a significant source of infection for Irish livestock.
PMID- 25127738
TI - Thyroid hormone regulation of hepatic lipid and carbohydrate metabolism.
AB - Thyroid hormone (TH) has important roles in regulating hepatic lipid,
cholesterol, and glucose metabolism. Recent findings suggest that clinical
conditions such as non-alcoholic fatty liver disease and type 2 diabetes
mellitus, which are associated with dysregulated hepatic metabolism, may involve
altered intracellular TH action. In addition, TH has key roles in lipophagy in
lipid metabolism, mitochondrial quality control, and the regulation of metabolic
genes. In this review, we discuss recent findings regarding the functions of TH
in hepatic metabolism, the relationship between TH and metabolic disorders, and
the potential therapeutic use of thyromimetics to treat metabolic dysfunction in
the liver.
PMID- 25127740
TI - Social class across the life course and physical activity at age 34 years in the
1970 British birth cohort.
AB - PURPOSE: To examine the associations between social class at ages 0, 5, 10, 30,
and 34 years and physical activity at age 34 years using a novel approach to
analysis of life course data. METHODS: We used structural equation modeling to
compare three competing models in life course epidemiology: the accumulation of
risk model with additive effects, the accumulation of risk model with trigger
effect, and the critical period model. Data were from a nationally representative
prospective cohort of 16,571 British men and women born in 1970. Outcomes were
physical activity during leisure time, during transports, and at work. RESULTS:
For all three domains of physical activity, for men and women, the accumulation
of risk model with additive effects fit the data best. In this model, social
class at ages 0, 5, 10, 30, and 34 years were associated with physical activity
at age 34 years, although the magnitude and the direction of the associations for
social class at each age varied by physical activity outcome and by sex.
CONCLUSIONS: Structural equation modeling appears to be a helpful tool in
selecting among competing models in life course epidemiology.
PMID- 25127739
TI - First-trimester nonsystemic corticosteroid use and the risk of oral clefts in
Norway.
AB - PURPOSE: Exposure of pregnant mice to corticosteroids can produce oral clefts in
offspring. Although data in humans are more mixed, recent reports have suggested
that dermatologic steroids are associated with oral clefts. METHODS: We
investigated maternal first-trimester exposure to corticosteroids (focusing on
dermatologic uses) and oral clefts in offspring using two population-based
studies. The Norway Cleft Study (1996-2001) is a national case-control study
including 377 infants with cleft lip +/- palate (CLP), 196 infants with cleft
palate only (CPO), and 763 controls. The Norwegian Mother and Child Cohort Study
(MoBa, 1998-2008) is a national birth cohort including 123 infants with CLP, 61
infants with CPO, and 551 controls. RESULTS: In the case-control study, there was
the suggestion of an association of dermatologic corticosteroids with both CLP
(adjusted OR [aOR], 2.3; 95% confidence interval [CI], 0.71-7.7) and CPO (aOR,
3.4; CI, 0.87-13). There was no evidence of this association in the cohort data
(odds ratio for CLP, 1.2; CI, 0.50-2.8 and odds ratio for CPO, 1.0; CI, 0.30
3.4), although exposure to dermatologic steroids was less specifically
ascertained. There were no associations with other types of corticosteroids.
CONCLUSIONS: Our data add to the suggestive but inconsistent findings for this
association.
PMID- 25127742
TI - In vivo hippocampal subfield volumes in schizophrenia and bipolar disorder.
AB - BACKGROUND: Hippocampal dysfunction and volume reductions have been reported in
patients with schizophrenia and bipolar disorder. The hippocampus consists of
anatomically distinct subfields. We investigated to determine whether in vivo
volumes of hippocampal subfields differ between clinical groups and healthy
control subjects. METHODS: Clinical examination and magnetic resonance imaging
were performed in 702 subjects (patients with schizophrenia spectrum [n = 210;
mean age, 32.0 +/- 9.3 (SD) years; 59% male], patients with bipolar spectrum [n =
192; mean age, 35.5 +/- 11.5 years; 40% male] and healthy control subjects [n =
300; mean age, 35.3 +/- 9.9 years; 53% male]). Hippocampal subfield volumes were
estimated with FreeSurfer. General linear models were used to explore diagnostic
differences in hippocampal subfield volumes, covarying for age, intracranial
volume, and medication. Post hoc analyses of associations to psychosis symptoms
(Positive and Negative Syndrome Scale) and cognitive function (verbal memory
[California Verbal Learning Test, second edition] and IQ [Wechsler Abbreviated
Scale of Intelligence]) were performed. RESULTS: Patient groups had smaller cornu
ammonis (CA) subfields CA2/3 (left, p = 7.2 * 10(-6); right, p = 2.3 * 10(-6)),
CA4/dentate gyrus (left, p = 1.4 * 10(-5); right, p = 2.3 * 10(-6)), subiculum
(left, p = 3.7 * 10(-6); right, p = 2.8 * 10(-8)), and right CA1 (p = .006)
volumes than healthy control subjects, but smaller presubiculum volumes were
found only in patients with schizophrenia (left, p = 6.7 * 10(-5); right, p = 1.6
* 10(-7)). Patients with schizophrenia had smaller subiculum (left, p = .035;
right, p = .031) and right presubiculum (p = .002) volumes than patients with
bipolar disorder. Smaller subiculum volumes were related to poorer verbal memory
in patients with bipolar disorder and healthy control subjects and to negative
symptoms in patients with schizophrenia. CONCLUSIONS: Hippocampal subfield volume
reductions are found in patients with schizophrenia and bipolar disorder. The
magnitude of reduction is greater in patients with schizophrenia, particularly in
the hippocampal outflow regions presubiculum and subiculum.
PMID- 25127741
TI - Neonatal maternal separation alters the capacity of adult neural precursor cells
to differentiate into neurons via methylation of retinoic acid receptor gene
promoter.
AB - BACKGROUND: Early life stress is thought to contribute to psychiatric disorders,
but the precise mechanisms underlying this link are poorly understood. As
neonatal stress decreases adult hippocampal neurogenesis, which, in turn,
functionally contributes to many behavioral phenotypes relevant to psychiatric
disorders, we examined how in vivo neonatal maternal separation (NMS) impacts the
capacity of adult hippocampal neural precursor cells via epigenetic alterations
in vitro. METHODS: Rat pups were separated from their dams for 3 hours daily from
postnatal day (PND) 2 to PND 14 or were never separated from the dam (as control
animals). We isolated adult neural precursor cells from the hippocampal dentate
gyrus at PND 56 and assessed rates of proliferation, apoptosis, and
differentiation in cell culture. We also evaluated the effect of DNA methylation
at the retinoic acid receptor (RAR) promoter stemming from NMS on adult neural
precursor cells. RESULTS: NMS attenuated neural differentiation of adult neural
precursor cells but had no detectible effect on proliferation, apoptosis, or
astroglial differentiation. The DNA methyltransferase (DNMT) inhibitor, 5-aza-dC,
reversed a reduction by NMS of neural differentiation of adult neural precursor
cells. NMS increased DNMT1 expression and decreased expression of RARalpha. An
RARalpha agonist increased neural differentiation and an antagonist reduced
retinoic acid-induced neural differentiation. NMS increased the methylated
portion of RARalpha promoter, and the DNMT inhibitor reversed a reduction by NMS
of RARalpha messenger RNA expression. CONCLUSIONS: NMS attenuates the capacity of
adult hippocampal neural precursor cells to differentiate into neurons by
decreasing expression of RARalpha through DNMT1-mediated methylation of its
promoter.
PMID- 25127744
TI - NAD homeostasis in the bacterial response to DNA/RNA damage.
AB - In mammals, NAD represents a nodal point for metabolic regulation, and its
availability is critical to genome stability. Several NAD-consuming enzymes are
induced in various stress conditions and the consequent NAD decline is generally
accompanied by the activation of NAD biosynthetic pathways to guarantee NAD
homeostasis. In the bacterial world a similar scenario has only recently begun to
surface. Here we review the current knowledge on the involvement of NAD
homeostasis in bacterial stress response mechanisms. In particular, we focus on
the participation of both NAD-consuming enzymes (DNA ligase, mono(ADP-ribosyl)
transferase, sirtuins, and RNA 2'-phosphotransferase) and NAD biosynthetic
enzymes (both de novo, and recycling enzymes) in the response to DNA/RNA damage.
As further supporting evidence for such a link, a genomic context analysis is
presented showing several conserved associations between NAD homeostasis and
stress responsive genes.
PMID- 25127743
TI - Disruption of the potassium channel regulatory subunit KCNE2 causes iron
deficient anemia.
AB - Iron homeostasis is a dynamic process that is tightly controlled to balance iron
uptake, storage, and export. Reduction of dietary iron from the ferric to the
ferrous form is required for uptake by solute carrier family 11 (proton-coupled
divalent metal ion transporters), member 2 (Slc11a2) into the enterocytes. Both
processes are proton dependent and have led to the suggestion of the importance
of acidic gastric pH for the absorption of dietary iron. Potassium voltage-gated
channel subfamily E, member 2 (KCNE2), in combination with potassium voltage
gated channel, KQT-like subfamily, member 1 (KCNQ1), form a gastric potassium
channel essential for gastric acidification. Deficiency of either Kcne2 or Kcnq1
results in achlorhydia, gastric hyperplasia, and neoplasia, but the impact on
iron absorption has not, to our knowledge, been investigated. Here we report that
Kcne2-deficient mice, in addition to the previously reported phenotypes, also
present with iron-deficient anemia. Interestingly, impaired function of KCNQ1
results in iron-deficient anemia in Jervell and Lange-Nielsen syndrome patients.
We speculate that impaired function of KCNE2 could result in the same clinical
phenotype.
PMID- 25127745
TI - Bacterial colonization of the ovarian bursa in dogs with clinically suspected
pyometra and in controls.
AB - Septic peritonitis occurs relatively commonly in dogs. Secondary septic
peritonitis is usually associated with perforation of intestines or infected
viscera, such as the uterus in pyometra cases. The aim of this study was to
evaluate the bacterial flora in the ovarian bursae of intact bitches as a
potential source of contamination. One hundred forty dogs, clinically suspected
of pyometra, were prospectively enrolled. The control group consisted of 26 dogs
that underwent elective ovariohysterectomies and 18 dogs with mammary gland
tumors that were neutered at the time of mastectomy. Bacteriology samples were
taken aseptically at the time of surgery from the bursae and the uterus in all
dogs. Twenty-two dogs that were clinically suspected of pyometra had sterile
uterine content ("mucometra" cases); the remaining 118 had positive uterine
cultures ("pyometra" cases) and septic peritoneal fluid was present in 10% of
these cases. Of the 118 pyometra cases, 9 had unilateral and 15 had bilateral
bacterial colonization of their ovarian bursae. However, the bacteria from the
ovarian bursa were similar to those recovered from the uterine pus in only half
of the cases. Furthermore, positive bursae were also seen in one mucometra dog
(unilateral) and in four control dogs (two unilateral and two bilateral). The
data illustrate that the canine ovarian bursa can harbor bacteria. The biological
importance of these isolations remains unclear.
PMID- 25127746
TI - [Alterations in arterial compliance of dyslipidemic patients].
AB - INTRODUCTION: We studied the alteration on the distensibility of the arterial
walls caused by dyslipidemia LDLc dependent, along the decades of life, by means
of a study of the radial artery pulse wave. METHODS: We made an analysis of the
radial artery pulse wave records acquired by means a movement displacement
sensor, placed on radial palpation area. We recruited 100 dyslipidemic men
without other cardiovascular risk factors, between the 3rd and the 6th decade. We
identified the reflected wave in the records and we computed the augmentation
index in order to quantify its amplitude and position. This index is useful to
assess the endothelial dysfunction. Besides, we defined a velocity coefficient as
the ratio between the size of the individuals and the delay time between the peak
of the systolic wave and the arrival of the reflected wave. Results were compared
against those obtained in a group of 161 healthy volunteers. RESULTS: We found
that dyslipidemic patients presented augmentation index values similar to
controls until the fourth decade, increasing thereafter with significant
differences only in the 6th decade. No significant differences were found in the
velocity index in any of the ages studied. CONCLUSIONS: We conclude that
alterations produced by dyslipidemia take decades to manifest, and they begin
affecting the mechanism of vasodilation of distal arteries with highest
proportion of smooth muscle, without altering the proximal conduit arteries with
more elastin content.
PMID- 25127747
TI - [Impact of plasma pro-B-type natriuretic peptide amino-terminal and galectin-3
levels on the predictive capacity of the LIPID Clinical Risk Scale in stable
coronary disease].
AB - INTRODUCTION: At present, there is no tool validated by scientific societies for
risk stratification of patients with stable coronary artery disease (SCAD). It
has been shown that plasma levels of monocyte chemoattractant protein-1 (MCP-1),
galectin-3 and pro-B-type natriuretic peptide amino-terminal (NT-proBNP) have
prognostic value in this population. OBJECTIVE: To analyze the prognostic value
of a clinical risk scale published in Long-term Intervention with Pravastatin in
Ischemic Disease (LIPID) study and determining its predictive capacity when
combined with plasma levels of MCP-1, galectin-3 and NT-proBNP in patients with
SCAD. METHODS AND RESULTS: A total of 706 patients with SCAD and a history of
acute coronary syndrome (ACS) were analyzed over a follow up period of 2.2 +/-
0.99 years. The primary endpoint was the occurrence of an ischemic event (any
SCA, stroke or transient ischemic attack), heart failure, or death. A clinical
risk scale derived from the LIPID study significantly predicted the development
of the primary endpoint, with an area under the ROC curve (Receiver Operating
Characteristic) of 0.642 (0.579 to 0.705); P<0.001. A composite score was
developed by adding the scores of the LIPID and scale decile levels of MCP -1,
galectin -3 and NT-proBNP. The predictive value improved with an area under the
curve of 0.744 (0.684 to 0.805); P<0.001 (P=0.022 for comparison). A score
greater than 21.5 had a sensitivity of 74% and a specificity of 61% for the
development of the primary endpoint (P<0.001, log -rank test). CONCLUSION: Plasma
levels of MCP-1, galectin -3 and NT-proBNP improve the ability of the LIPID
clinical scale to predict the prognosis of patients with SCAD.
PMID- 25127749
TI - Production of a value added compound from the H-acid waste water-Bioflocculants
by Klebsiella pneumoniae.
AB - A novel strain (designated as ZCY-7) which could convert H-acid into
bioflocculants was isolated from H-acid wastewater sludge. Conditions for
bioflocculants production were optimized by response surface methodology (RSM)
and determined to be inoculum size 9.65%, initial pH 7.0, and CODCr of the H-acid
wastewater 520mg/L. The highest flocculating efficiency achieved for kaolin
suspension was 95.1%, after 60h cultivation. The yielded bioflocculant was mainly
composed of polysaccharide (82.4%) and protein (14.2%), and maintained its
flocculating activity in 0.4% (w/w) kaolin suspensions over pH 2-8 and 20-80
degrees C. Fourier transform infrared (FTIR) spectra showed that amino, amide and
hydroxyl groups were present in the bioflocculant molecules. A viable alternative
treatment technology of H-acid wastewater using this novel strain is suggested,
which could largely reduce bioflocculants costs. In addition, flocculating
mechanism investigation reveals that the bioflocculant could cause kaolin
suspension instability by means of charge neutralization firstly and then
promoted the aggregation of suspension particles by adsorption and bridge. It is
evident from the results that H-acid wastewater could be used as a source to
manufacture bioflocculants.
PMID- 25127750
TI - The chloramphenicol acetyltransferase vector as a tool for stable tagging of
Neospora caninum.
AB - Neospora caninum is an obligate intracellular Apicomplexa, a phylum where one of
the current methods for functional studies relies on molecular genetic tools. For
Toxoplasma gondii, the first method described, in 1993, was based on resistance
against chloramphenicol. As in T. gondii, we developed a vector constituted of
the chloramphenicol acetyltransferase gene (CAT) flanked by the N. caninum
dihydrofolate reductase-thymidylate synthase (DHFR-TS) 5' coding sequence
flanking region. Five weeks after transfection and under the selection of
chloramphenicol the expression of CAT increased compared to the wild type and the
resistance was retained for more than one year. Between the stop codon of CAT and
the 3' UTR of DHFR, a Lac-Z gene controlled by the N. caninum tubulin 5' coding
sequence flanking region was ligated, resulting in a vector with a reporter gene
(Ncdhfr-CAT/NcTub-tetO/Lac-Z). The stability was maintained through an episomal
pattern for 14 months when the tachyzoites succumbed, which was an unexpected
phenomenon compared to T. gondii. Stable parasites expressing the Lac-Z gene
allowed the detection of tachyzoites after invasion by enzymatic reaction (CPRG)
and were visualised macro- and microscopically by X-Gal precipitation and
fluorescence. This work developed the first vector for stable expression of
proteins based on chloramphenicol resistance and controlled exclusively by N.
caninum promoters.
PMID- 25127751
TI - Degradation of the mechanical properties of orthodontic NiTi alloys in the oral
environment: an in vitro study.
AB - Appropriate characterization studies are needed to demonstrate the mechanical and
biological effects of interaction between archwires and the oral environment. The
aim of this study was to investigate, in vitro, the impact of this acidic and
fluoridated environment on the electrochemical behavior and the mechanical
properties of orthodontic alloys in nickel titanium and in stainless steel
(controls) for the following parameters: Young's modulus (E), elastic limit
(sigmae) and the maximum tensile load (sigmam). Six samples of each archwire
alloy were used to assess these parameters. An Instron universal test apparatus
(model - 88512) was used for the traction tests on the wires after immersion in
solutions at different concentrations of fluoride and at various pH levels.
Observations were made using an electron scanning microscope (ESM) to evaluate
the surface and an ICP (inductively coupled plasma) mass spectroscopy analysis
was made to quantify the substances released into the immersion solution. For the
NiTi archwires, immersion in the fluoridated and acidic medium showed a
statistically significant reduction of the Young's modulus (E), the elastic limit
(sigmae) and the maximum tensile load (sigmam). Similarly, a higher level of
released nickel proportionate to the increase in the fluoride concentration and
acidity was observed in the immersion solutions. ESM observations revealed the
status of the surface of the different alloys and the presence of corrosive
pitting.
PMID- 25127753
TI - Dental sequellae of alveolar clefts: utility of endosseous implants. Part II:
clinical cases.
AB - This second part follows on from part 1 published in the previous issue of this
journal. The aim of this publication is to offer teams specializing in the
primary and secondary treatment of labio-alveolar-palatal clefts a prosthetic
evaluation for more rational management of the dental sequellae of clefts for
patients who, when they reach adulthood, often wish to improve their facial
esthetics, in which the dental element plays an important part. The
reorganization and restoration of the maxillary anterior teeth and their esthetic
integration with respect to the face and lips would then be less of a problem for
plastic surgeons and orthodontists. In this regard, the installation in this
sector of implants, following ambitious bone surgery involving the sacrifice of
the teeth of the medial nasal process in bilateral forms, is a protocol that
could usefully be taken into account.
PMID- 25127755
TI - ZnO nanoparticles induced adjuvant effect via toll-like receptors and Src
signaling in Balb/c mice.
AB - Our previous studies indicated that zinc oxide nanoparticles (ZnO NPs) have
adjuvant properties to a known allergen ovalbumin (OVA) in Balb/c mice.
Therefore, in this study, we focused on the mechanisms involved in adjuvant
responses induced by ZnO NPs. The eosinophil counts in the Peyers' patches of
intestine and ICAM-1, Cox2 protein expressions were enhanced in the ZnO NPs/OVA
group. Following screening of toll-like receptors (TLRs), TLR 2, 4 and 6 were
found to be increased. Accordingly, we found that downstream proteins of TLRs
such as myeloid differentiation primary response protein-88 (MyD88), IL-1
receptor associated kinase 1 (IRAK 1), and TNFR-associated factor 6 (TRAF 6) were
also found to be enhanced in the ZnO NPs/OVA-induced group. These inflammatory
responses underlined the critical roles of TLRs in the inflammatory response. ZnO
NPs increased the mRNA levels of inflammatory cytokine IL-1beta and protein
expression of several mediators, including Cox2, PGE2, MMP-9 and finally caspase
1 in macrophages. Another pathway for adjuvant effect is Src which was found to
be significantly affected by the activation of p-Lyn, p-Syk, IP3, p-PLC-gamma and
cAMP. Ca(2+) influx was significantly increased as well in the ZnO NPs/OVA group.
These findings demonstrated the differential role of TLRs in regulation of the
ZnO NPs-induced adjuvant responses causing the inflammation. We therefore,
conclude that ZnO NPs have significant adjuvant effect via following Src kinase
and TLRs signaling that ascribed to inflammatory responses due to recruitment and
activation of adhesion molecules and inflammatory cells. The adjuvant property of
ZnO NPs may help in planning strategies for its therapeutic use.
PMID- 25127756
TI - Compensatory effects of hOGG1 for hMTH1 in oxidative DNA damage caused by
hydrogen peroxide.
AB - OBJECTIVE: To investigate the potential compensatory effects of hOGG1 and hMTH1
in the repair of oxidative DNA damage. METHODS: The hOGG1 and hMTH1 gene
knockdown human embryonic pulmonary fibroblast cell lines were established by
lentivirus-mediated RNA interference. The messenger RNA (mRNA) levels of hOGG1
and hM1TH1 were analyzed by the real-time polymerase chain reaction, and 8
hydroxy-2'-deoxyguanosine (8-oxo-dG) formation was analyzed in a high-performance
liquid chromatography-electrochemical detection system. RESULTS: The hOGG1 and
hMTH1 knockdown cells were obtained through blasticidin selection. After
transfection of hOGG1 and hMTH1 small interfering RNA, the expression levels of
the mRNA of hOGG1 and hMTH1 genes were decreased by 97.2% and 96.2%,
respectively. The cells then were exposed to 100 MUmol/L of hydrogen peroxide
(H2O2) for 12 h to induce oxidative DNA damage. After H2O2 exposure, hMTH1 mRNA
levels were increased by 25% in hOGG1 gene knockdown cells, whereas hOGG1 mRNA
levels were increased by 52% in hMTH1 gene knockdown cells. Following the
treatment with H2O2, the 8-oxo-dG levels in the DNA of hOGG1 gene knockdown cells
were 3.1-fold higher than those in untreated HFL cells, and 1.67-fold higher than
those in H2O2-treated wild-type cells. The 8-oxo-dG levels in hMTH1 gene
knockdown cells were 2.3-fold higher than those in untreated human embryonic
pulmonary fibroblast cells, but did not differ significantly from those in H2O2
treated wild-type cells. CONCLUSION: Our data suggested that hOGG1 could
compensate for hMTH1 during oxidative DNA damage caused by H2O2, whereas hMTH1
could not compensate sufficiently for hOGG1 during the process.
PMID- 25127757
TI - Insulin-like growth factor binding protein 5 (IGFBP5) mediates methamphetamine
induced dopaminergic neuron apoptosis.
AB - Overexposure to methamphetamine (METH), a psychoactive drug, induces a variety of
adverse effects to the nervous system, including apoptosis of dopaminergic
neurons. Insulin-like growth factor binding protein 5 (IGFBP5), a member of
insulin-like growth factor (IGF) system, is a pro-apoptotic factor that plays
important roles in neuronal apoptosis. To test the hypothesis that IGFBP5 can
mediate METH-induced neuronal apoptosis, we examined IGFBP5 mRNA and protein
expression changes in PC12 cells exposed to METH (3.0mM) for 24h and in the
striatum of rats following 15 mg/kg * 8 intraperitoneal injections of METH at 12h
interval. We also checked the effect on neuronal apoptosis after silencing IGFBP5
expression with TUNEL staining and flow cytometry; Western blot was used for
detecting the expression of apoptotic markers active-caspase3 and PARP. To
elucidate the mechanisms underlying IGFBP5-mediated neuronal apoptosis, we
determined the release of cytochrome c (cyto c), an apoptogenic factor, from the
mitochondria after METH treatment with or without IGFBP5 knockdown. Our results
showed that IGFBP5 expression was increased significantly after METH exposure in
PC12 cells and in the METH-treated rats' striatum. Further, METH-exposed PC12
cells exhibited higher apoptosis-positive cell number and activity of caspase3
and PARP compared with control cells, while these changes can be blocked by
silencing IGFBP5 expression. In addition, a significant increase of cyto c
release from mitochondria after METH exposure was observed and it was inhibited
after silencing IGFBP5 expression in PC12 cells. These results indicate that
IGFBP5 plays key roles in METH-induced neuronal apoptosis and may be a potential
gene target for therapeutics in METH-caused neurotoxicity.
PMID- 25127748
TI - Pegylated interferon plus ribavirin in HIV-infected patients with recurrent
hepatitis C after liver transplantation: a prospective cohort study.
AB - BACKGROUND & AIMS: The aim of this study was to evaluate the results of treatment
with pegylated interferon and ribavirin for the recurrence of hepatitis C after
liver transplantation in HCV/HIV-coinfected patients. METHODS: This was a
prospective, multicentre cohort study, including 78 HCV/HIV-coinfected liver
transplant patients who received treatment for recurrent hepatitis C. For
comparison, we included 176 matched HCV-monoinfected patients who underwent liver
transplantation during the same period of time at the same centres and were
treated for recurrent hepatitis C. RESULTS: Antiviral therapy was discontinued
prematurely in 56% and 39% (p = 0.016), mainly because of toxicity (22% and 11%,
respectively; p=0.034). Sustained virological response (SVR) was achieved in 21%
of the coinfected patients and in 36% of monoinfected patients (p = 0.013). For
genotype 1, SVR rates were 10% and 33% (p = 0.002), respectively; no significant
differences were observed for the other genotypes. A multivariate analysis based
on the whole series identified HIV-coinfection as an independent predictor of
lack of SVR (OR, 0.17; 95% CI, 0.06-0.42). Other predictors of SVR were donor
age, pretreatment HCV viral load, HCV genotype, and early virological response.
SVR was associated with a significant improvement in survival: 5-year survival
after antiviral treatment was 79% for HCV/HIV-coinfected patients with SVR vs.
43% for those without (p = 0.02) and 92% vs. 60% in HCV-monoinfected patients (p
< 0.001), respectively. CONCLUSIONS: The response to pegylated interferon and
ribavirin was poorer in HCV/HIV-coinfected liver recipients, particularly those
with genotype 1. However, when SVR was achieved, survival of coinfected patients
increased significantly.
PMID- 25127758
TI - A human ether-a-go-go-related (hERG) ion channel atomistic model generated by
long supercomputer molecular dynamics simulations and its use in predicting drug
cardiotoxicity.
AB - Acquired cardiac long QT syndrome (LQTS) is a frequent drug-induced toxic event
that is often caused through blocking of the human ether-a-go-go-related (hERG)
K(+) ion channel. This has led to the removal of several major drugs post
approval and is a frequent cause of termination of clinical trials. We report
here a computational atomistic model derived using long molecular dynamics that
allows sensitive prediction of hERG blockage. It identified drug-mediated hERG
blocking activity of a test panel of 18 compounds with high sensitivity and
specificity and was experimentally validated using hERG binding assays and patch
clamp electrophysiological assays. The model discriminates between potent, weak,
and non-hERG blockers and is superior to previous computational methods. This
computational model serves as a powerful new tool to predict hERG blocking thus
rendering drug development safer and more efficient. As an example, we show that
a drug that was halted recently in clinical development because of severe
cardiotoxicity is a potent inhibitor of hERG in two different biological assays
which could have been predicted using our new computational model.
PMID- 25127759
TI - The education of UK specialised neonatal nurses: reviewing the rationale for
creating a standard competency framework.
AB - This paper examines the influences surrounding formal education provision for
specialised neonatal nurses in the UK and presents a standardised clinical
competency framework in response. National drivers for quality neonatal care
define links to the numbers and ratios of specialised neonatal nurses in
practice. Historical changes to professional nursing governance have led to
diversity in supporting education programmes, making achievement of a standard
level of clinical competence for this element of the nursing workforce difficult.
In addition responsibility for funding specialised education and training has
moved from central to local hospital level. Evaluating these key influences on
education provision rationalised the development, by a UK professional consensus
group, of a criteria based framework to be utilised by both formal education and
service providers. The process identified clinical competency (in terms of unique
knowledge and skills), evidence of achievement, and quality education principles.
Access to specialised education relies on the availability of programmes of study
and clear funding strategies. Creating a core syllabus for education provides a
tool to standardise course content, commission education and audit clinical
competency. In addition partnerships between healthcare and education providers
become successful in achieving standard specialised education for neonatal
nurses.
PMID- 25127845
TI - How to evaluate appendices with borderline diameters on CT: proposal of a quick
solution to overcome the limitations of the established CT criteria.
AB - RATIONALE AND OBJECTIVES: To propose a useful computed tomography (CT) criterion,
the diameter with compression (DWC), especially in appendices with borderline
diameters. MATERIALS AND METHODS: We retrospectively collected 216 patients with
visible appendices on CT after clinicopathologic confirmation of appendicitis.
Each CT criterion of appendicitis was evaluated by an experienced abdominal
radiologist: maximal outer diameter (MOD), DWC, mural thickness and enhancement,
periappendiceal infiltration, and appendicolith. DWC is the expected diameter
after deduction of the intraluminal compressible contents such as air and feces.
All the CT criteria were compared in the appendicitis and nonappendicitis group.
RESULTS: The areas under the receiver operating characteristic curve (AUC) of the
MOD and the DWC were 0.967 and 0.973, respectively. The optimal cutoff value was
8.2 mm for the MOD and 6.6 mm for the DWC. Twenty-five of the 80 appendicitis
patients (31.2%) and 62 of the 136 nonappendicitis patients (45.6%) had MODs
between 5.7 mm and 9.8 mm in the overlap between the two groups. In this overlap,
the AUC of the MODs declined sharply to 0.767, whereas the AUC of the DWCs
remained 0.923. Use of the criterion of DWC >6.6 mm yielded a sensitivity of
84.0%, a specificity of 88.7%, and an accuracy of 87.4%. There were no other
criteria with both sensitivity and specificity >80% in the range of overlap.
CONCLUSIONS: The proposed CT criterion of the DWC is not affected by normal
distension or periappendiceal inflammation but only by true appendicitis.
Therefore, DWC can improve the diagnostic performance of appendicitis regardless
of the MOD.
PMID- 25127846
TI - Use of contrast-enhanced spectral mammography for intramammary cancer staging:
preliminary results.
AB - RATIONALE AND OBJECTIVES: To prospectively evaluate and compare the accuracy of
contrast-enhanced spectral mammography (CESM) and ultrasound (US) in size
measurement of breast cancer with histologic tumor sizes as gold standard.
MATERIALS AND METHODS: Twenty women aged between 40-73 years (mean age, 57 +/- 10
years) with histologically proven invasive ductal/lobular carcinomas were
included in the study. Agreement between imaging tumor size (CESM and US) and
histopathologic tumor size was evaluated with Bland-Altman analysis.
Stereotactically guided vacuum biopsy was performed in four patients after CESM.
Two independent reviewers described artifacts of CESM. RESULTS: Motion artifacts
did not occur in the study. CESM-specific artifacts caused by scattered radiation
mostly occurred in oblique view of CESM. Background enhancement of breast tissue
was seen in four patients. Mean difference of tumor sizes was 0.3 mm (6.34%)
between CESM and histology and -2.2 mm (-7.59%) between US and histology. Limits
of agreement ranged from -18.9 to 19.48 mm for CESM and from -17.1 to 12.7 mm
with US. Especially smaller tumors with a size <23 mm were measured more
precisely with CESM. Enhancement of breast tissue around microcalcifications
correlated with abnormalities. CONCLUSIONS: CESM is accurate in size measurements
of small breast tumors. On average CESM leads to a slight overestimation of tumor
size, whereas US tends to underestimate tumor size. Assessment of the breast
tissue can be limited by the scattered radiation artifact and background
enhancement of breast tissue. CESM seems to be helpful in the characterization of
breast tissue around microcalcifications.
PMID- 25127847
TI - Simple and efficient method for region of interest value extraction from picture
archiving and communication system viewer with optical character recognition
software and macro program.
AB - RATIONALE AND OBJECTIVES: The objectives are: 1) to introduce a simple and
efficient method for extracting region of interest (ROI) values from a Picture
Archiving and Communication System (PACS) viewer using optical character
recognition (OCR) software and a macro program, and 2) to evaluate the accuracy
of this method with a PACS workstation. MATERIALS AND METHODS: This module was
designed to extract the ROI values on the images of the PACS, and created as a
development tool by using open-source OCR software and an open-source macro
program. The principal processes are as follows: (1) capture a region of the ROI
values as a graphic file for OCR, (2) recognize the text from the captured image
by OCR software, (3) perform error-correction, (4) extract the values including
area, average, standard deviation, max, and min values from the text, (5)
reformat the values into temporary strings with tabs, and (6) paste the temporary
strings into the spreadsheet. This principal process was repeated for the number
of ROIs. The accuracy of this module was evaluated on 1040 recognitions from 280
randomly selected ROIs of the magnetic resonance images. The input times of ROIs
were compared between conventional manual method and this extraction module
assisted input method. RESULTS: The module for extracting ROI values operated
successfully using the OCR and macro programs. The values of the area, average,
standard deviation, maximum, and minimum could be recognized and error-corrected
with AutoHotkey-coded module. The average input times using the conventional
method and the proposed module-assisted method were 34.97 seconds and 7.87
seconds, respectively. CONCLUSIONS: A simple and efficient method for ROI value
extraction was developed with open-source OCR and a macro program. Accurate
inputs of various numbers from ROIs can be extracted with this module. The
proposed module could be applied to the next generation of PACS or existing PACS
that have not yet been upgraded.
PMID- 25127848
TI - Effect of light and vigorous physical activity on balance and gait of older
adults.
AB - This study aims to quantitatively assess the effects of vigorous and light
physical activity (VPA, LPA) on static balance, gait and sit-to-stand (STS) tasks
in a cohort of healthy older adults. To this end, 34 individuals of age >65 years
were divided into two groups (n=17 each) who underwent 36 sessions (3*12 weeks)
of PA characterized by different levels of intensity, assessed through continuous
heart rate monitoring during the training session. Their balance and mobility
were objectively evaluated on the basis of postural sway and time of STS
measurements performed using a force platform. The main spatiotemporal parameters
of gait (i.e. speed, stride and gait cycle duration, stance, swing and double
support phase duration) were also acquired using a wearable inertial measurement
unit. The results show that most gait parameters and STS time significantly
improve in the VPA group but not in the LPA one. For the latter group a reduction
only of swing phase duration was detected. PA also induced a generalized
reduction of postural sway in both groups in the case of absence of visual input.
These findings suggest that PA programs characterized by superior levels of
intensity might be more suitable in generally improving static and dynamic daily
motor tasks, while in terms of static balance acceptable results can be achieved
even when only light activity is performed.
PMID- 25127850
TI - Differential expression of estrogen receptor alpha in the embryonic adrenal
kidney-gonadal complex of the oviparous lizard, Calotes versicolor (Daud.).
AB - Estrogen signalling is critical for ovarian differentiation in reptiles with
temperature-dependent sex determination (TSD). To elucidate the involvement of
estrogen in this process, adrenal-kidney-gonadal (AKG) expression of estrogen
receptor (ERalpha) was studied at female-producing temperature (FPT) in the
developing embryos of the lizard, Calotes versicolor which exhibits a distinct
pattern of TSD. The eggs of this lizard were incubated at 31.5+/-0.5 degrees C
(100% FPT). The torso of embryos containing adrenal-kidney-gonadal complex (AKG)
was collected during different stages of development and subjected to Western
blotting and immunohistochemistry analysis. The ERalpha antibody recognized two
protein bands with apparent molecular weight ~55 and ~45kDa in the total protein
extracts of embryonic AKG complex of C. versicolor. The observed results suggest
the occurrence of isoforms of ERalpha. The differential expression of two
different protein isoforms may reveal their distinct role in cell proliferation
during gonadal differentiation. This is the first report to reveal two isoforms
of the ERalpha in a reptile during development. Immunohistochemical studies
reveal a weak, but specific, cytoplasmic ERalpha immunostaining exclusively in
the AKG during late thermo-sensitive period suggesting the responsiveness of AKG
to estrogens before gonadal differentiation at FPT. Further, cytoplasmic as well
as nuclear expression of ERalpha in the medulla and in oogonia of the cortex
(faint activity) at gonadal differentiation stage suggests that the onset of
gonadal estrogen activity coincides with sexual differentiation of gonad.
Intensity and pattern of the immunoreactions of ERalpha in the medullary region
at FPT suggest endogenous production of estrogen which may act in a paracrine
fashion to induce neighboring cells into ovarian differentiation pathway.
PMID- 25127849
TI - Bothrops jararacussu snake venom-induces a local inflammatory response in a
prostanoid- and neutrophil-dependent manner.
AB - Local tissue reactions provoked by Bothrops venoms are characterized by edema,
hemorrhage, pain, and inflammation; however, the mechanisms of tissue damage vary
depending upon the species of snake. Here, we investigated the mechanisms
involved in the local inflammatory response induced by the Bothrops jararacussu
venom (BjcuV). Female Swiss mice were injected with either saline, BjcuV (0.125-8
MUg/paw) or loratadine (an H1 receptor antagonist), compound 48/80 (for mast cell
depletion), capsaicin (for C-fiber desensitization), infliximab (an anti-TNF
alpha antibody), indomethacin (a non-specific COX inhibitor), celecoxib (a
selective COX-2 inhibitor) or fucoidan (a P- and L-selectins modulator) given
before BjcuV injection. Paw edema was measured by plethysmography. In addition,
paw tissues were collected for the measurement of myeloperoxidase activity, TNF
alpha and IL-1 levels, and COX-2 immunoexpression. The direct chemotactic effect
of BjcuV and the in vitro calcium dynamic in neutrophils were also investigated.
BjcuV caused an edematogenic response with increased local production of TNF
alpha and IL-1beta as well as COX-2 expression. Both edema and neutrophil
migration were prevented by pretreatment with indomethacin, celecoxib or
fucoidan. Furthermore, BjcuV induced a direct in vitro neutrophil chemotaxis by
increasing intracellular calcium. Therefore, BjcuV induces an early onset edema
dependent upon prostanoid production and neutrophil migration.
PMID- 25127851
TI - Advanced diffusion MRI fiber tracking in neurosurgical and neurodegenerative
disorders and neuroanatomical studies: A review.
AB - Diffusion MRI enabled in vivo microstructural imaging of the fiber tracts in the
brain resulting in its application in a wide range of settings, including in
neurological and neurosurgical disorders. Conventional approaches such as
diffusion tensor imaging (DTI) have been shown to have limited applications due
to the crossing fiber problem and the susceptibility of their quantitative
indices to partial volume effects. To overcome these limitations, the recent
focus has shifted to the advanced acquisition methods and their related
analytical approaches. Advanced white matter imaging techniques provide superior
qualitative data in terms of demonstration of multiple crossing fibers in their
spatial orientation in a three dimensional manner in the brain. In this review
paper, we discuss the advancements in diffusion MRI and introduce their roles.
Using examples, we demonstrate the role of advanced diffusion MRI-based fiber
tracking in neuroanatomical studies. Results from its preliminary application in
the evaluation of intracranial space occupying lesions, including with respect to
future directions for prognostication, are also presented. Building upon the
previous DTI studies assessing white matter disease in Huntington's disease and
Amyotrophic lateral sclerosis; we also discuss approaches which have led to
encouraging preliminary results towards developing an imaging biomarker for these
conditions.
PMID- 25127852
TI - [Meningitis to Candida albicans at the adult, use of the new diagnosis methods].
AB - Candida albicans or non-albicans are a frequent source of infection but seldom
displayed in cerebrospinal fluid although responsible of an important number of
nosocomial meningitis. Diagnosis is difficult which often delays treatment, which
in turn hinders prognostic. This clinical case shows a patient afflicted with a
deadly C. albicans meningitis and allows us to focus on new diagnostic tools and
advice against this infection.
PMID- 25127853
TI - Intraoperative management of heart-lung interactions: "from hypothetical
prediction to improved titration".
AB - Extensive literature describes the suitability of dynamic parameters to predict
responsiveness in fluid. However, based on heart-lung interactions, these
parameters can have serious limitations, including the use of protective lung
ventilation. Although the latter seems to be beneficial for healthy patients
undergoing high-risk surgery, the intraoperative interpretation of dynamic
parameters to predict fluid responsiveness can be hazardous. In this context, the
attending physician could, alternatively, titrate the need of fluids with a small
fluid challenge, which remains unaffected by low tidal volume, the presence of
arrhythmia, or the presence of spontaneous ventilation. When intraoperative
prediction of fluid responsiveness is required in mechanically ventilated
patients, "improved" titration should be preferred to a hypothetical prediction.
PMID- 25127854
TI - Auditory feedback perturbation in children with developmental speech sound
disorders.
AB - BACKGROUND/PURPOSE: Several studies indicate a close relation between auditory
and speech motor functions in children with speech sound disorders (SSD). The aim
of this study was to investigate the ability to compensate and adapt for
perturbed auditory feedback in children with SSD compared to age-matched normally
developing children. METHOD: 17 normally developing children aged 4.1-8.7 years
(mean=5.5, SD=1.4), and 11 children with SSD aged 3.9-7.5 years (mean=5.1,
SD=1.0) participated in the study. Auditory feedback was perturbed by real-time
shifting the first and second formant of the vowel /e/ during the production of
CVC words in a five-step paradigm (practice/familiarization; start/baseline;
ramp; hold; end/release). RESULTS: At the group level, the normally developing
children were better able to compensate and adapt, adjusting their formant
frequencies in the direction opposite to the perturbation, while the group of
children with SSD followed (amplifying) the perturbation. However, large
individual differences lie underneath. Furthermore, strong correlations were
found between the amount of compensation and performance on oral motor movement
non-word repetition tasks. CONCLUSIONS: Results suggested that while most
children with SSD can detect incongruencies in auditory feedback and can adapt
their target representations, they are unable to compensate for perturbed
auditory feedback. These findings suggest that impaired auditory-motor
integration may play a key role in SSD. LEARNING OUTCOMES: The reader will be
able to: (1) describe the potential role of auditory feedback control in
developmental speech disorders (SSD); (2) identify the neural control subsystems
involved in feedback based speech motor control; (3) describe the differences
between compensation and adaptation for perturbed auditory feedback; (4) explain
why auditory-motor integration may play a key role in SSD.
PMID- 25127855
TI - The ataxia telangiectasia mutated and cyclin D3 proteins cooperate to help
enforce TCRbeta and IgH allelic exclusion.
AB - Coordination of V rearrangements between loci on homologous chromosomes is
critical for Ig and TCR allelic exclusion. The Ataxia Telangietasia mutated (ATM)
protein kinase promotes DNA repair and activates checkpoints to suppress aberrant
Ig and TCR rearrangements. In response to RAG cleavage of Igkappa loci, ATM
inhibits RAG expression and suppresses further Vkappa-to-Jkappa rearrangements to
enforce Igkappa allelic exclusion. Because V recombination between alleles is
more strictly regulated for TCRbeta and IgH loci, we evaluated the ability of ATM
to restrict biallelic expression and V-to-DJ recombination of TCRbeta and IgH
genes. We detected greater frequencies of lymphocytes with biallelic expression
or aberrant V-to-DJ rearrangement of TCRbeta or IgH loci in mice lacking ATM. A
preassembled DJbeta complex that decreases the number of TCRbeta rearrangements
needed for a productive TCRbeta gene further increased frequencies of ATM
deficient cells with biallelic TCRbeta expression. IgH and TCRbeta proteins drive
proliferation of prolymphocytes through cyclin D3 (Ccnd3), which also inhibits VH
transcription. We show that inactivation of Ccnd3 leads to increased frequencies
of lymphocytes with biallelic expression of IgH or TCRbeta genes. We also show
that Ccnd3 inactivation cooperates with ATM deficiency to increase the
frequencies of cells with biallelic TCRbeta or IgH expression while decreasing
the frequency of ATM-deficient lymphocytes with aberrant V-to-DJ recombination.
Our data demonstrate that core components of the DNA damage response and cell
cycle machinery cooperate to help enforce IgH and TCRbeta allelic exclusion and
indicate that control of V-to-DJ rearrangements between alleles is important to
maintain genomic stability.
PMID- 25127856
TI - Idiotype-specific Th cells support oligoclonal expansion of anti-dsDNA B cells in
mice with lupus.
AB - Systemic lupus erythematosus (SLE) is marked by a Th cell-dependent B cell
hyperresponsiveness, with frequent germinal center reactions and
hypergammaglobulinemia. The specificity of Th cells in lupus remains unclear, but
B cell Ids have been suggested. A hallmark is the presence of anti-dsDNA, mutated
IgG autoantibodies with a preponderance of arginines in CDR3 of the Ig variable H
chain (IgVH). B cells can present V region-derived Id peptides on their MHC class
II molecules to Id-specific Th cells. We show that Id-specific Th cells support
the proliferation of anti-dsDNA Id(+) B cells in mice suffering from systemic
autoimmune disease with SLE-like features. Mice developed marked clonal
expansions of B cells; half of the IgVH sequences were clonally related. Anti
dsDNA B cells made up 40% of B cells in end-stage disease. The B cells expressed
mutated IgVH with multiple arginines in CDR3. Hence, Id-driven T cell-B cell
collaboration supported the production of classical anti-dsDNA Abs,
recapitulating the characteristics of such Abs in SLE. The results support the
concept that Id-specific Th cells may trigger the development of SLE and suggest
that manipulation of the Id-specific T cell repertoire could play a role in
treatment.
PMID- 25127857
TI - Myeloid-specific disruption of tyrosine phosphatase Shp2 promotes alternative
activation of macrophages and predisposes mice to pulmonary fibrosis.
AB - The alternative activation of M2 macrophages in the lungs has been implicated as
a causative agent in pulmonary fibrosis; however, the mechanisms underlying M2
polarization are poorly characterized. In this study, we investigated the role of
the ubiquitously expressed Src homology domain-containing tyrosine phosphatase
Shp2 in this process. Shp2 inactivation augmented IL-4-mediated M2 polarization
in vitro, suggesting that Shp2 regulates macrophage skewing and prevents a bias
toward the M2 phenotype. Conditional removal of Shp2 in monocytes/macrophages
with lysozyme M promoter-driven Cre recombinase caused an IL-4-mediated shift
toward M2 polarization. Additionally, an increase in arginase activity was
detected in Shp2(?/?) mice after i.p. injection of chitin, whereas Shp2-deficient
macrophages showed enhanced M2 polarization and protection against schistosome
egg-induced schistosomiasis. Furthermore, mutants were more sensitive than
control mice to bleomycin-induced inflammation and pulmonary fibrosis. Shp2 was
associated with IL-4Ralpha and inhibited JAK1/STAT6 signaling through its
phosphatase activity; loss of Shp2 promoted the association of JAK1 with IL
4Ralpha, which enhanced IL-4-mediated JAK1/STAT6 activation that resulted in M2
skewing. Taken together, these findings define a role for Shp2 in alveolar
macrophages and reveal that Shp2 is required to inhibit the progression of M2
associated pulmonary fibrosis.
PMID- 25127858
TI - Role of TGF-beta signaling in generation of CD39+CD73+ myeloid cells in tumors.
AB - There is growing evidence that generation of adenosine from ATP, which is
mediated by the CD39/CD73 enzyme pair, predetermines immunosuppressive and
proangiogenic properties of myeloid cells. We have previously shown that the
deletion of the TGF-beta type II receptor gene (Tgfbr2) expression in myeloid
cells is associated with decreased tumor growth, suggesting protumorigenic effect
of TGF-beta signaling. In this study, we tested the hypothesis that TGF-beta
drives differentiation of myeloid-derived suppressor cells into protumorigenic
terminally differentiated myeloid mononuclear cells (TDMMCs) characterized by
high levels of cell-surface CD39/CD73 expression. We found that TDMMCs represent
a major cell subpopulation expressing high levels of both CD39 and CD73 in the
tumor microenvironment. In tumors isolated from mice with spontaneous tumor
formation of mammary gland and conditional deletion of the type II TGF-beta
receptor in mammary epithelium, an increased level of TGF-beta protein was
associated with further increase in number of CD39(+)CD73(+) TDMMCs compared with
MMTV-PyMT/TGFbetaRII(WT) control tumors with intact TGF-beta signaling. Using
genetic and pharmacological approaches, we demonstrated that the TGF-beta
signaling mediates maturation of myeloid-derived suppressor cells into TDMMCs
with high levels of cell surface CD39/CD73 expression and adenosine-generating
capacity. Disruption of TGF-beta signaling in myeloid cells resulted in decreased
accumulation of TDMMCs, expressing CD39 and CD73, and was accompanied by
increased infiltration of T lymphocytes, reduced density of blood vessels, and
diminished progression of both Lewis lung carcinoma and spontaneous mammary
carcinomas. We propose that TGF-beta signaling can directly induce the generation
of CD39(+)CD73(+) TDMMCs, thus contributing to the immunosuppressive,
proangiogenic, and tumor-promoting effects of this pleiotropic effector in the
tumor microenvironment.
PMID- 25127860
TI - Differences in the transduction of canonical Wnt signals demarcate effector and
memory CD8 T cells with distinct recall proliferation capacity.
AB - Protection against reinfection is mediated by Ag-specific memory CD8 T cells,
which display stem cell-like function. Because canonical Wnt (Wingless/Int1)
signals critically regulate renewal versus differentiation of adult stem cells,
we evaluated Wnt signal transduction in CD8 T cells during an immune response to
acute infection with lymphocytic choriomeningitis virus. Whereas naive CD8 T
cells efficiently transduced Wnt signals, at the peak of the primary response to
infection only a fraction of effector T cells retained signal transduction and
the majority displayed strongly reduced Wnt activity. Reduced Wnt signaling was
in part due to the downregulation of Tcf-1, one of the nuclear effectors of the
pathway, and coincided with progress toward terminal differentiation. However,
the correlation between low and high Wnt levels with short-lived and memory
precursor effector cells, respectively, was incomplete. Adoptive transfer studies
showed that low and high Wnt signaling did not influence cell survival but that
Wnt high effectors yielded memory cells with enhanced proliferative potential and
stronger protective capacity. Likewise, following adoptive transfer and
rechallenge, memory cells with high Wnt levels displayed increased recall
expansion, compared with memory cells with low Wnt signaling, which were
preferentially effector-like memory cells, including tissue-resident memory
cells. Thus, canonical Wnt signaling identifies CD8 T cells with enhanced
proliferative potential in part independent of commonly used cell surface markers
to discriminate effector and memory T cell subpopulations. Interventions that
maintain Wnt signaling may thus improve the formation of functional CD8 T cell
memory during vaccination.
PMID- 25127859
TI - Release of active TGF-beta1 from the latent TGF-beta1/GARP complex on T
regulatory cells is mediated by integrin beta8.
AB - Activated T regulatory cells (Tregs) express latent TGF-beta1 on their cell
surface bound to GARP. Although integrins have been implicated in mediating the
release of active TGF-beta1 from the complex of latent TGF-beta1 and latent TGF
beta1 binding protein, their role in processing latent TGF-beta1 from the latent
TGF-beta1/GARP complex is unclear. Mouse CD4(+)Foxp3(+) Treg, but not
CD4(+)Foxp3(-) T cells, expressed integrin beta8 (Itgb8) as detected by
quantitative RT-PCR. Itgb8 expression was a marker of thymically derived (t)Treg,
because it could not be detected on Foxp3(+)Helios(-) Tregs or on Foxp3(+) T
cells induced in vitro. Tregs from Itgb8 conditional knockouts exhibited normal
suppressor function in vitro and in vivo in a model of colitis but failed to
provide TGF-beta1 to drive Th17 or induced Treg differentiation in vitro. In
addition, Itgb8 knockout Tregs expressed higher levels of latent TGF-beta1 on
their cell surface consistent with defective processing. Thus, integrin
alphavbeta8 is a marker of tTregs and functions in a cell intrinsic manner in
mediating the processing of latent TGF-beta1 from the latent TGF-beta1/GARP
complex on the surface of tTregs.
PMID- 25127861
TI - The N-terminal domain of NLRC5 confers transcriptional activity for MHC class I
and II gene expression.
AB - Ag presentation to CD4(+) and CD8(+) T cells depends on MHC class II and MHC
class I molecules, respectively. One important regulatory factor of this process
is the transcriptional regulation of MHC gene expression. It is well established
that MHC class II transcription relies on the NLR protein CIITA. Recently,
another NLR protein, NLRC5, was shown to drive MHC class I expression. The
molecular mechanisms of the function of NLRC5 however remain largely elusive. In
this study, we present a detailed functional study of the domains of NLRC5
revealing that the N-terminal domain of human NLRC5 has intrinsic transcriptional
activity. Domain swapping experiments between NLRC5 and CIITA showed that this
domain contributes to MHC class I and MHC class II gene expression with a bias
for activation of MHC class I promoters. Delivery of this construct by adeno
associated viral vectors upregulated MHC class I and MHC class II expression in
human cells and enhanced lysis of melanoma cells by CD8(+) cytotoxic T cells in
vitro. Taken together, this work provides novel insight into the function of
NLRC5 and CIITA in MHC gene regulation.
PMID- 25127862
TI - The expression of sphingosine-1 phosphate receptor-1 in chronic lymphocytic
leukemia cells is impaired by tumor microenvironmental signals and enhanced by
piceatannol and R406.
AB - Chronic lymphocytic leukemia (CLL) is characterized by the progressive
accumulation of clonal B lymphocytes. Proliferation occurs in lymphoid tissues
upon interaction of leukemic cells with a supportive microenvironment. Therefore,
the mobilization of tissue-resident CLL cells into the circulation is a useful
therapeutic strategy to minimize the reservoir of tumor cells within survival
niches. Because the exit of normal lymphocytes from lymphoid tissues depends on
the presence of sphingosine-1 phosphate (S1P) and the regulated expression of S1P
receptor-1 (S1PR1), we investigated whether the expression and function of S1PR1
can be modulated by key microenvironment signals. We found that activation of CLL
cells with CXCL12, fibroblast CD40L(+), BCR cross-linking, or autologous nurse
like cells reduces their S1PR1 expression and the migratory response toward S1P.
Moreover, we found that S1PR1 expression was reduced in the
proliferative/activated subset of leukemic cells compared with the quiescent
subset from the same patient. Similarly, bone marrow-resident CLL cells
expressing high levels of the activation marker CD38 showed a lower expression of
S1PR1 compared with CD38(low) counterparts. Finally, given that treatment with
BCR-associated kinase inhibitors induces a transient redistribution of leukemic
cells from lymphoid tissues to circulation, we studied the effect of the Syk
inhibitors piceatannol and R406 on S1PR1 expression and function. We found that
they enhance S1PR1 expression in CLL cells and their migratory response toward
S1P. Based on our results, we suggest that the regulated expression of S1PR1
might modulate the egress of the leukemic clone from lymphoid tissues.
PMID- 25127863
TI - Concomitant TLR/RLH signaling of radioresistant and radiosensitive cells is
essential for protection against vesicular stomatitis virus infection.
AB - Several studies indicated that TLR as well as retinoic acid-inducible gene I-like
helicase (RLH) signaling contribute to vesicular stomatitis virus (VSV)-mediated
triggering of type I IFN (IFN-I) responses. Nevertheless, TLR-deficient MyD88(-/
)Trif(-/-) mice and RLH-deficient caspase activation and recruitment domain
adaptor inducing IFN-beta (Cardif)(-/-) mice showed only marginally enhanced
susceptibility to lethal VSV i.v. infection. Therefore, we addressed whether
concomitant TLR and RLH signaling, or some other additional mechanism, played a
role. To this end, we generated MyD88(-/-)Trif(-/-)Cardif(-/-) (MyTrCa(-/-)) mice
that succumbed to low-dose i.v. VSV infection with similar kinetics as IFN-I
receptor-deficient mice. Three independent approaches (i.e., analysis of IFN
alpha/beta serum levels, experiments with IFN-beta reporter mice, and
investigation of local IFN-stimulated gene induction) revealed that MyTrCa(-/-)
mice did not mount IFN-I responses following VSV infection. Of note, treatment
with rIFN-alpha protected the animals, qualifying MyTrCa(-/-) mice as a model to
study the contribution of different immune cell subsets to the production of
antiviral IFN-I. Upon adoptive transfer of wild-type plasmacytoid dendritic cells
and subsequent VSV infection, MyTrCa(-/-) mice displayed significantly reduced
viral loads in peripheral organs and showed prolonged survival. On the contrary,
adoptive transfer of wild-type myeloid dendritic cells did not have such effects.
Analysis of bone marrow chimeric mice revealed that TLR and RLH signaling of
radioresistant and radiosensitive cells was required for efficient protection.
Thus, upon VSV infection, plasmacytoid dendritic cell-derived IFN-I primarily
protects peripheral organs, whereas concomitant TLR and RLH signaling of
radioresistant stroma cells as well as of radiosensitive immune cells is needed
to effectively protect against lethal disease.
PMID- 25127864
TI - Dopamine inhibits the effector functions of activated NK cells via the
upregulation of the D5 receptor.
AB - Several lines of evidence indicate that dopamine (DA) plays a key role in the
cross-talk between the nervous and immune systems. In this study, we disclose a
novel immune-regulatory role for DA: inhibition of effector functions of
activated NK lymphocytes via the selective upregulation of the D5 dopaminergic
receptor in response to prolonged cell stimulation with rIL-2. Indeed, engagement
of this D1-like inhibitory receptor following binding with DA suppresses NK cell
proliferation and synthesis of IFN-gamma. The inhibition of IFN-gamma production
occurs through blocking the repressor activity of the p50/c-REL dimer of the NF
kappaB complex. Indeed, the stimulation of the D5 receptor on rIL-2-activated NK
cells inhibits the binding of p50 to the microRNA 29a promoter, thus inducing a
de novo synthesis of this miRNA. In turn, the increased levels of microRNA 29a
were inversely correlated with the ability of NK cells to produce IFN-gamma.
Taken together, our findings demonstrated that DA switches off activated NK
cells, thus representing a checkpoint exerted by the nervous system to control
the reactivity of these innate immune effectors in response to activation stimuli
and to avoid the establishment of chronic and pathologic inflammatory processes.
PMID- 25127865
TI - The late endosomal transporter CD222 directs the spatial distribution and
activity of Lck.
AB - The spatial and temporal organization of T cell signaling molecules is
increasingly accepted as a crucial step in controlling T cell activation. CD222,
also known as the cation-independent mannose 6-phosphate/insulin-like growth
factor 2 receptor, is the central component of endosomal transport pathways. In
this study, we show that CD222 is a key regulator of the early T cell signaling
cascade. Knockdown of CD222 hampers the effective progression of TCR-induced
signaling and subsequent effector functions, which can be rescued via
reconstitution of CD222 expression. We decipher that Lck is retained in the
cytosol of CD222-deficient cells, which obstructs the recruitment of Lck to CD45
at the cell surface, resulting in an abundant inhibitory phosphorylation
signature on Lck at the steady state. Hence, CD222 specifically controls the
balance between active and inactive Lck in resting T cells, which guarantees
operative T cell effector functions.
PMID- 25127867
TI - Sodium dodecyl sulfate polyacrylamide gel electrophoresis for direct quantitation
of protein adsorption.
AB - A simple method, sodium dodecyl sulfate polyacrylamide gel electrophoresis
coupled with direct protein adsorption analysis (SDS-PAGE/DPA), is presented here
for the quantitation of adsorption-caused protein loss. No complicated steps and
expensive equipment are involved, and this method is capable of measuring
proteins adsorbed on sample vials at extremely low concentrations (in pg/MUl). We
used this method to characterize the effects of concentration, time, and volume
on adsorption. We also applied this method to discover differential sample loss
in protein mixtures and its utility in developing preventive strategies of
adsorption.
PMID- 25127868
TI - Synthesis and evaluation of novel alkannin and shikonin oxime derivatives as
potent antitumor agents.
AB - A set of forty alkannin and shikonin oxime derivatives were firstly designed and
synthesized. Their cytotoxicities against three kinds of tumor cells and a normal
cell line were tested and compared with alkannin and shikonin. The cell-based
investigation demonstrated that some oxime derivatives were more or comparatively
effective to the lead compounds, especially their selective and excellent
antitumor activities towards K562 cells with no toxicity in normal cells. We may
conclude that oximate modification to the mother nucleus of alkannin and shikonin
is an available approach to acquire potent antitumor agents.
PMID- 25127866
TI - D-beta-hydroxybutyrate extends lifespan in C. elegans.
AB - The ketone body beta-hydroxybutyrate (betaHB) is a histone deacetylase (HDAC)
inhibitor and has been shown to be protective in many disease models, but its
effects on aging are not well studied. Therefore we determined the effect of
betaHB supplementation on the lifespan ofC. elegans nematodes. betaHB
supplementation extended mean lifespan by approximately 20%. RNAi knockdown of
HDACs hda-2 or hda-3 also increased lifespan and further prevented betaHB
mediated lifespan extension. betaHB-mediated lifespan extension required the DAF
16/FOXO and SKN-1/Nrf longevity pathways, the sirtuin SIR-2.1, and the AMP kinase
subunit AAK-2. betaHB did not extend lifespan in a genetic model of dietary
restriction indicating that betaHB is likely functioning through a similar
mechanism. betaHB addition also upregulated BetaHB dehydrogenase activity and
increased oxygen consumption in the worms. RNAi knockdown of F55E10.6, a short
chain dehydrogenase and SKN-1 target gene, prevented the increased lifespan and
betaHB dehydrogenase activity induced by betaHB addition, suggesting that
F55E10.6 functions as an inducible betaHB dehydrogenase. Furthermore, betaHB
supplementation increased worm thermotolerance and partially prevented glucose
toxicity. It also delayed Alzheimer's amyloid-beta toxicity and decreased
Parkinson's alpha-synuclein aggregation. The results indicate that D-betaHB
extends lifespan through inhibiting HDACs and through the activation of conserved
stress response pathways.
PMID- 25127869
TI - Development of potential selective and reversible pyrazoline based MAO-B
inhibitors as MAO-B PET tracer precursors and reference substances for the early
detection of Alzheimer's disease.
AB - Since high MAO-B levels are present in early stages of AD, the MAO-B system can
be designated as an appropriate and prospective tracer target of molecular
imaging biomarkers for the detection of early AD. According to the preceding
investigations of Mishra et al. the aim of this work was the development of a
compound library of selective and reversible MAO-B inhibitors by performing
bioisosteric modifications of the core structure of 3-(anthracen-9-yl)-5-phenyl
4,5-dihydro-1H-pyrazoles. In conclusion, 13 new pyrazoline based derivatives have
been prepared, which will serve as precursor substances for future radiolabeling
as well as reference compounds for the investigation of increased MAO-B levels in
AD.
PMID- 25127870
TI - Submonomer synthesis of azapeptide ligands of the Insulin Receptor Tyrosine
Kinase domain.
AB - Azapeptide ligands of the Insulin Receptor Tyrosine Kinase (IRTK) were developed
by solid-phase submonomer azapeptide synthesis in sufficient isolated yields (36
55%) and purities >95% for structure-activity relationship studies. The
azapeptides adopted folded geometries with some proportion of random coil
according to CD and NMR spectroscopy. In vitro phosphorylation of the IRTK domain
in the presence of azapeptides produced a lead inhibitor, Ac-DIazaYET-NH2 (~50%
at 400 MUM) whereas the [aza-DOPA(3)] and [aza-Glu(4)] analogs were found to
stimulate IRTK phosphorylations. Thus, azapeptide ligands of the IRTK provide
important modulatory activity of this important class of enzymes for anti-cancer
and related applications in drug discovery.
PMID- 25127871
TI - Synthesis and insecticidal activity of new deoxypodophyllotoxin derivatives
modified in the D-ring.
AB - In continuation of our program aimed at the discovery of new natural-product
based insecticidal agents, twenty-six deoxypodophyllotoxin derivatives modified
in the D-ring were synthesized and evaluated as insecticidal agents against the
pre-third-instar larvae of oriental armyworm, Mythimna separata (Walker) in vivo
at 1 mg/mL. The configuration of three compounds 3, 4, and IIIi was unambiguously
determined by single-crystal X-ray diffraction. It demonstrated that aminolysis
of deoxypodophyllotoxin in the presence of pyrrolidine and piperidine could
result in complete inversion of the configuration of the carbonyl group at its C
2 position. Five compounds IIa, IIi-k, and IIIh showed the equal or higher
insecticidal activity than toosendanin. Especially IIj displayed the most potent
insecticidal activity with the final mortality rate of 65.5%.
PMID- 25127872
TI - Cryopreservation of hepatocyte (HepG2) cell monolayers: impact of trehalose.
AB - A simple method to cryogenically preserve hepatocyte monolayers is currently not
available but such a technique would facilitate numerous applications in the
field of biomedical engineering, cell line development, and drug screening. We
investigated the effect of trehalose and dimethyl sulfoxide (Me2SO) in
cryopreservation of human hepatocellular carcinoma (HepG2) cells in suspension
and monolayer formats. HepG2 cell monolayers were incubated for 24h at varying
concentrations of trehalose (50-150 mM) prior to cryopreservation to identify the
optimum concentration for such preincubation. When trehalose alone was used as
the cryoprotective agent (CPA), cells in monolayer format did not survive
freezing while cells in suspension demonstrated 14% viability 24h after thawing.
Only 6-13% of cells in monolayers survived freezing in cell culture medium
supplemented with 10% Me2SO, but 42% of cells were recovered successfully if
monolayers were preincubated with 100 mM trehalose prior to freezing in the Me2SO
supplemented medium. Interestingly, for cells frozen in suspension in presence of
10% Me2SO, metabolic activity immediately following thawing did not change
appreciably compared to unfrozen control cells. Finally, Raman spectroscopy
techniques were employed to evaluate ice crystallization in the presence and
absence of trehalose in freezing solutions without cells because crystallization
may alter the extent of injury observed in cell monolayers. We speculate that
biomimetic approaches of using protective sugars to preserve cells in monolayer
format will facilitate the development of techniques for long-term preservation
of human tissues and organs in the future.
PMID- 25127873
TI - Influence of hydroxyapatite nanoparticles on the viscosity of dimethyl sulfoxide
H2O-NaCl and glycerol-H2O-NaCl ternary systems at subzero temperatures.
AB - The viscosity, at subzero temperatures, of ternary solutions commonly used in
cryopreservation is tremendously important for understanding ice formation and
molecular diffusion in biopreservation. However, this information is scarce in
the literature. In addition, to the best of our knowledge, the effect of
nanoparticles on the viscosity of these solutions has not previously been
reported. The objectives of this study were thus: (i) to systematically measure
the subzero viscosity of two such systems, dimethyl sulfoxide (Me2SO)-H2O-NaCl
and glycerol-H2O-NaCl; (ii) to explore the effect of hydroxyapatite (HA)
nanoparticles on the viscosity; and (iii) to provide models that precisely
predict viscosity at multiple concentrations of cryoprotective agent (CPA) in
saline solutions at subzero temperatures. Our experiments were performed in two
parts. We first measured the viscosity at multiple CPA concentrations [0.3-0.75
(w/w)] in saline solution with and without nanoparticles at subzero temperatures
(0 to -30 degrees C). The data exhibited a good fit to the Williams-Landel-Ferry
(WLF) equation. We then measured the viscosity of residual unfrozen ternary
solutions with and without nanoparticles during equilibrium freezing. HA
nanoparticles made the solution more viscous, suggesting applications for these
nanoparticles in preventing cell dehydration, ice nucleation, and ice growth
during freezing and thawing in cryopreservation.
PMID- 25127874
TI - The effects of cryopreservation on cells isolated from adipose, bone marrow and
dental pulp tissues.
AB - The effects of cryopreservation on mesenchymal stem cell (MSC) phenotype are not
well documented; however this process is of increasing importance for
regenerative therapies. This study examined the effect of cryopreservation (10%
dimethyl-sulfoxide) on the morphology, viability, gene-expression and relative
proportion of MSC surface-markers on cells derived from rat adipose, bone marrow
and dental pulp. Cryopreservation significantly reduced the number of viable
cells in bone marrow and dental pulp cell populations but had no observable
effect on adipose cells. Flow cytometry analysis demonstrated significant
increases in the relative expression of MSC surface-markers, CD90 and CD29/CD90
following cryopreservation. sqRT-PCR analysis of MSC gene-expression demonstrated
increases in pluripotent markers for adipose and dental pulp, together with
significant tissue-specific increases in CD44, CD73-CD105 following
cryopreservation. Cells isolated from different tissue sources did not respond
equally to cryopreservation with adipose tissue representing a more robust source
of MSCs.
PMID- 25127875
TI - Cytotoxic T lymphocytes block tumor growth both by lytic activity and IFNgamma
dependent cell-cycle arrest.
AB - To understand global effector mechanisms of CTL therapy, we performed microarray
gene expression analysis in a murine model using pmel-1 T-cell receptor (TCR)
transgenic T cells as effectors and B16 melanoma cells as targets. In addition to
upregulation of genes related to antigen presentation and the MHC class I
pathway, and cytotoxic effector molecules, cell-cycle-promoting genes were
downregulated in the tumor on days 3 and 5 after CTL transfer. To investigate the
impact of CTL therapy on the cell cycle of tumor cells in situ, we generated B16
cells expressing a fluorescent ubiquitination-based cell-cycle indicator (B16
fucci) and performed CTL therapy in mice bearing B16-fucci tumors. Three days
after CTL transfer, we observed diffuse infiltration of CTLs into the tumor with
a large number of tumor cells arrested at the G1 phase of the cell cycle, and the
presence of spotty apoptotic or necrotic areas. Thus, tumor growth suppression
was largely dependent on G1 cell-cycle arrest rather than killing by CTLs.
Neutralizing antibody to IFNgamma prevented both tumor growth inhibition and G1
arrest. The mechanism of G1 arrest involved the downregulation of S-phase kinase
associated protein 2 (Skp2) and the accumulation of its target cyclin-dependent
kinase inhibitor p27 in the B16-fucci tumor cells. Because tumor-infiltrating
CTLs are far fewer in number than the tumor cells, we propose that CTLs
predominantly regulate tumor growth via IFNgamma-mediated profound cytostatic
effects rather than via cytotoxicity. This dominance of G1 arrest over other
mechanisms may be widespread but not universal because IFNgamma sensitivity
varied among tumors.
PMID- 25127876
TI - Combined submandibular gland flap and sternocleidomastoid musculocutaneous flap
for postoperative reconstruction in older aged patients with oral cavity and
oropharyngeal cancers.
AB - BACKGROUND: The growth of aging populations in an increasing number of countries
has led to a concomitant increase in the incidence of chronic diseases.
Accordingly, the proportion of older aged patients with oral cavity and
oropharyngeal cancers and comorbidities has also increased. Thus, improvements
must be made in the tolerance and safety of surgical procedures for these
patients with complex medical conditions. In this study, we investigated combined
submandibular gland flap and sternocleidomastoid musculocutaneous flap for
postoperative reconstruction in older aged patients with oral cavity and
oropharyngeal cancers in terms of surgical methods, safety, and clinical outcome.
METHODS: Between January 2011 and May 2012, 8 patients over the age of 65 years
(7 men, 1 woman; aged 66 to 75 years (median, 69.6)) with oral cavity and
oropharyngeal cancers underwent combined submandibular gland and
sternocleidomastoid myocutaneous flaps for postoperative reconstruction at
Ganzhou Tumor Hospital. All eight patients had comorbid cardiovascular,
cerebrovascular, or chronic respiratory disease or diabetes. Clinical outcomes,
complications, and tolerance to surgical treatment were observed. RESULTS:
Surgical treatment was successful in all eight patients. All submandibular gland
flaps survived with well-mucosalized surfaces and with no complications. During
the postoperative follow-up period of 12 to 28 months, no patient developed local
recurrence or distant metastasis, and all had good recovery of function and local
contour. CONCLUSIONS: This combined reconstruction technique enables appropriate
restoration of oral function, facial aesthetics and improved quality of life.
Further, this technique has several advantages: it is easier to perform, reduces
operation time and surgical risk, causes less surgical injury, and has minor
impact on contour. The technique provides a new and safe reconstruction option
for older aged patients with oral cavity and oropharyngeal cancers.
PMID- 25127877
TI - Molecular assembly of the period-cryptochrome circadian transcriptional repressor
complex.
AB - The mammalian circadian clock is driven by a transcriptional-translational
feedback loop, which produces robust 24-hr rhythms. Proper oscillation of the
clock depends on the complex formation and periodic turnover of the Period and
Cryptochrome proteins, which together inhibit their own transcriptional activator
complex, CLOCK-BMAL1. We determined the crystal structure of the CRY-binding
domain (CBD) of PER2 in complex with CRY2 at 2.8 A resolution. PER2-CBD adopts a
highly extended conformation, embracing CRY2 with a sinuous binding mode. Its N
terminal end tucks into CRY adjacent to a large pocket critical for CLOCK-BMAL1
binding, while its C-terminal half flanks the CRY2 C-terminal helix and
sterically hinders the recognition of CRY2 by the FBXL3 ubiquitin ligase.
Unexpectedly, a strictly conserved intermolecular zinc finger, whose integrity is
important for clock rhythmicity, further stabilizes the complex. Our structure
guided analyses show that these interspersed CRY-interacting regions represent
multiple functional modules of PERs at the CRY-binding interface.
PMID- 25127879
TI - Management of adrenal incidentaloma.
AB - Improvements in medical imaging have resulted in the incidental discovery of many
silent and unrecognized adrenal tumors. The term "adrenal incidentaloma" (AI) is
applied to any adrenal mass>=1cm in its longest axis that is discovered
incidentally during abdominal imaging that was not performed to specifically
evaluate adrenal pathology. These incidentalomas may be either secretory or non
secretory, benign or malignant. Distinctive characteristics of these lesions must
be determined by the clinician to determine appropriate management. Such
distinctions are based on laboratory findings and imaging, principally CT with
and without contrast injection. Investigations must be carefully chosen to avoid
ordering unnecessary and expensive tests for too many patients while, at the same
time, avoiding the risk of failing to diagnose a secreting malignant or tumor.
These examinations will determine patient care: surgery or surveillance. When
simple surveillance is chosen, specific criteria must be met with regard to
diagnostic modalities (clinical, imaging, laboratory testing) and its duration.
PMID- 25127878
TI - Effect of a qigong intervention program on telomerase activity and psychological
stress in abused Chinese women: a randomized, wait-list controlled trial.
AB - BACKGROUND: Abused women, who suffer from chronic psychological stress, have been
shown to have shorter telomeres than never abused women. Telomere shortening is
associated with increased risk of cell death, and it is believed that adopting
health-promoting behaviors can help to increase the activity of telomerase, an
enzyme that counters telomere shortening. Qigong is an ancient Chinese mind-body
integration, health-oriented practice designed to enhance the function of qi, an
energy that sustains well-being. Therefore, an assessor-blind, randomized, wait
list controlled trial was developed to evaluate the effect of a qigong
intervention on telomerase activity (primary objective) and proinflammatory
cytokines, perceived stress, perceived coping, and depressive symptoms (secondary
objectives) in abused Chinese women. METHODS/DESIGN: A total of 240 Chinese
women, aged >= 18 years, who have been abused by an intimate partner within the
past three years will be recruited from a community setting in Hong Kong and
randomized to receive either a qigong intervention or wait-list control condition
as follows: the qigong intervention will comprise (i) a 2-hour group qigong
training session twice a week for 6 weeks, (ii) a 1-hour follow-up group qigong
exercise session once a week for 4 months, and (iii) a 30-minute self-practice
qigong exercise session once a day for 5.5 months. The wait-list control group
will receive qigong training after the intervention group completes the program.
Upon completion of the qigong intervention program, it is expected that abused
Chinese women in the intervention group will have higher levels of telomerase
activity and perceived coping and lower levels of proinflammatory cytokines,
perceived stress, and depressive symptoms than will abused Chinese women in the
wait-list control group. DISCUSSION: This study will provide information about
the effect of qigong exercise on telomerase activity and chronic psychological
stress in abused Chinese women. The findings will inform the design of
interventions to relieve the effects of IPV-related psychological stress on
health. Also, the concept that health-promoting behaviors could slow down
cellular aging might even motivate abused women to change their lifestyles. TRIAL
REGISTRATION: Current Controlled Trials NCT02060123. Registered February 6, 2014.
PMID- 25127880
TI - An inevitable wave of prescription drug monitoring programs in the context of
prescription opioids: pros, cons and tensions.
AB - BACKGROUND: In an effort to control non-medical use and/or medical abuse of
prescription drugs, particularly prescription opioids, electronic prescription
drug monitoring programs (PDMP) have been introduced in North-American countries,
Australia and some parts of Europe. Paradoxically, there are simultaneous
pressures to increase opioid prescribing for the benefit of individual patients
and to reduce it for the sake of public health, and this pressure warrants a
delicate balance of appropriate therapeutic uses of these drugs with the risk of
developing dependence. This article discusses pros and cons of PDMP in reducing
diversion of prescription opioids, without hampering access to those medications
for those with genuine needs, and highlights tensions around PDMP implementation.
DISCUSSION: PDMPs may help alleviate diversion, over-prescription and fraudulent
prescribing/dispensing; prompt drug treatment referrals; avoid awkward drug urine
test; and inform spatial changes in prescribing practices and help designing
tailored interventions. Fear of legal retribution, privacy and data security,
potential confusion about addiction and pseudo-addiction, and potential undue
pressure of detecting misuse/diversion - are the major problems. There are
tensions about unintended consequence of excessive regulatory enforcements,
corresponding collateral damages particularly about inadequate prescribing for
patients with genuine needs, and mandatory consultation requirements of PDMP.
SUMMARY: In this era of information technology PDMP is likely to flourish and
remain with us for a long time. A clear standard of practice against which
physicians' care will be judged may expedite the utilisation of PDMP. In
addition, adequate training on addiction and pain management along with public
awareness, point-of-supply data entry from pharmacy, point-of-care real-time
access to data, increasing access to addiction treatment and appropriate
regulatory enforcement preferably through healthcare administration, together,
may help remove barriers to PDMP use.
PMID- 25127881
TI - Palmoplantar pustules and osteoarticular pain in a 42-year-old woman.
AB - Key teaching points * Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO)
syndrome is characterized by distinctive osteoarticular manifestations and a
spectrum of neutrophilic dermatoses. * The most common dermatologic
manifestations include palmoplantar pustulosis, acne conglobata, and acne
fulminans. * SAPHO syndrome should be considered in patients presenting
osteoarticular pain, particularly involving the anterior chest wall and/or spine,
and neutrophilic skin lesions.
PMID- 25127883
TI - Chronic pancreatitis of the pancreatic remnant is an independent risk factor for
pancreatic fistula after distal pancreatectomy.
AB - BACKGROUND: There is an ongoing debate about the best closure technique after
distal pancreatectomy (DP). The aim of the closure is to prevent the formation of
a clinically relevant post-operative pancreatic fistula (POPF). Stapler technique
seems to be equal compared with hand-sewn closure of the remnant. For both
techniques, a fistula rate of approximately 30% has been reported. METHODS: We
retrospectively analyzed our DPs between 01/2000 and 12/2010. In all cases, the
pancreatic duct was over sewn with a separately stitched ligation of the
pancreatic duct (5*0 PDS) followed by a single-stitched hand-sewn closure of the
residual pancreatic gland. The POPF was classified according to the criteria of
the International Study Group for Pancreatic Fistula (ISGPF). Univariate and
multivariate analyses of potential risk factors for the formation of POPF were
performed. Indications for operations included cystic tumors (n = 53),
neuroendocrine tumors (n = 27), adenocarcinoma (n = 22), chronic pancreatitis (n
= 9), metastasis (n = 6), and others (n = 7). RESULTS: During the period, we
performed 124 DPs (? = 74, ? = 50). The mean age was 57.5 years (18-82). The POPF
rates according to the ISGPF criteria were: no fistula, 54.8% (n = 68); grade A,
24.2% (n = 30); grade B, 19.3% (n = 24); and grade C, 1.7% (n = 2). Therefore, in
21.0% (n = 26) of the cases, a clinically relevant pancreatic fistula occurred.
The mean postoperative stay was significantly higher after grade B/C fistula
(26.3 days) compared with no fistula/grade A fistula (13.7 days) (p < 0.05). The
uni- and multivariate analyses showed chronic pancreatitis of the pancreatic
remnant to be an independent risk factor for the development of POPF (p = 0.004
OR 7.09). CONCLUSION: By using a standardized hand-sewn closure technique of the
pancreatic remnant after DP with separately stitched ligation of the pancreatic
duct, a comparably low fistula rate can be achieved. Signs of chronic
pancreatitis of the pancreatic remnant may represent a risk factor for the
development of a pancreatic fistula after DP and therefore an anastomosis of the
remnant to the intestine should be considered.
PMID- 25127884
TI - Two transaldolase isogenes from Moniliella megachiliensis behave in a different
way depending on the stress class.
AB - We cloned and sequenced two transaldolase genes from Moniliella megachiliensis, a
microorganism known to produce a significant amount of erythritol under hyper
osmotic stress. The amino acid sequences encoded by these two genes (MmTAL1,
MmTAL2) showed 72% homology to each other. An AP-1 (ap response element)
associated with oxidative stress was found in the promoter region of MmTAL1,
while four STREs (stress response element) associated with osmotic stress were
found in the promoter region of MmTAL2. In early-stage cultivation (up to 2 h),
MmTAL1 was specifically expressed in response to oxidative stress generated by
the presence of 0.15 mM menadione; expression level 3-fold higher than before
stress loading. MmTAL2 was expressed in response to osmotic stress caused by 1.2
M NaCl; expression level was 21-fold higher than stress-free control. Erythritol
accumulated intracellularly under osmotic and oxidative stress, approximately 30
fold and 35-fold, respectively. We therefore concluded that M. megachiliensis
selectively uses two isogenes and produces erythritol during early-stage response
to stress, depending on the type of environmental stress.
PMID- 25127882
TI - High frequency of kdr L1014F is associated with pyrethroid resistance in
Anopheles coluzzii in Sudan savannah of northern Nigeria.
AB - BACKGROUND: Malaria burden is high in Nigeria, yet information on the major
mosquito vectors is lacking especially in the Sudan savannah region of the
country. In order to facilitate the design of future insecticide-based control
interventions in the region, this study has established the resistance profile of
An. gambiae s.l. populations in two northern Nigeria locations and assessed the
contribution of target site resistance mutations. METHODS: Larval collection was
conducted in two localities in Sudan savannah (Bunkure and Auyo) of northern
Nigeria between 2009 and 2011, from which resulting adult, female mosquitoes were
used for insecticides bioassays with deltamethrin, lambda-cyhalothrin, DDT and
malathion. The mosquitoes were identified to species level and molecular forms
and then genotyped for the presence of L1014F-kdr, L1014S-kdr and ace-1R
mutations. RESULTS: WHO bioassays revealed that An. gambiae s.l. from both
localities were highly resistant to lambda-cyhalothrin and DDT, but only
moderately resistant to deltamethrin. Full susceptibility was observed to
malathion. An. gambiae, M form (now An. coluzzii), was predominant over An.
arabiensis in Auyo and was more resistant to lambda-cyhalothrin than An.
arabiensis. No 'S' form (An. gambiae s.s.) was detected. A high frequency of 1014
F mutation (80.1%) was found in An. coluzzii in contrast to An. arabiensis
(13.5%). The presence of the 1014 F kdr allele was significantly associated with
resistance to lambda-cyhalothrin in An. coluzzii (OR = 9.85; P < 0.001) but not
in An. arabiensis. The L1014S-kdr mutation was detected in a single An.
arabiensis mosquito while no ace-1R mutation was found in any of the mosquitoes
analysed. CONCLUSIONS: The predominance of An. coluzzii and its resistance
profile to main insecticides described in this study can guide the implementation
of appropriate vector control interventions in this region of Nigeria where such
information was previously lacking.
PMID- 25127885
TI - Does vitamin A supplementation protect schoolchildren from acquiring soil
transmitted helminthiasis? A randomized controlled trial.
AB - BACKGROUND: Despite the intensive global efforts to control intestinal parasitic
infections, the prevalence of soil-transmitted helminth (STH) infections is still
very high in many developing countries particularly among children in rural
areas. METHODS: A randomized, double-blind, placebo-controlled trial was
conducted on 250 Aboriginal schoolchildren in Malaysia to investigate the effects
of a single high-dose of vitamin A supplementation (200,000 IU) on STH
reinfection. The effect of the supplement was assessed at 3 and 6 months after
receiving interventions; after a complete 3-day deworming course of 400 mg/daily
of albendazole tablets. RESULTS: Almost all children (98.6%) were infected with
at least one STH species. The overall prevalence of ascariasis, trichuriasis and
hookworm infection was 67.8%, 95.5% and 13.4%, respectively. Reinfection rates of
Ascaris, Trichuris and hookworm were high; at 6 months, assessment reached 80% of
the prevalence reported before treatment. There were no significant differences
in the reinfection rates and intensities of STH between vitamin A supplemented
children and those who received placebo at 3 and 6 months (p > 0.05).
CONCLUSIONS: Vitamin A supplementation showed no protective effect against STH
reinfection and this could be due to the high endemicity of STH in this
community. Long-term interventions to reduce poverty will help significantly in
reducing this continuing problem and there is no doubt that reducing intestinal
parasitic infection would have a positive impact on the health, nutrition and
education of these children. TRIAL REGISTRATION: This trial was registered at
clinicaltrials.gov as NCT00936091.
PMID- 25127886
TI - Estimates of adherence to treatment of vivax malaria.
AB - BACKGROUND: The relation between therapeutic failure and non-adherence to
treatment of malaria has been clearly established. Several measures have been
used to estimate adherence to Plasmodium vivax therapy, but few protocols have
been validated to ensure reliability of the estimates of adherence. The objective
of this study was to validate a five-item-reported-questionnaire derived from
original Morisky four-item scale to estimate adherence to P. vivax malaria
therapy. METHODS: A five-item-reported questionnaire was applied to patients
after treatment of P. vivax malaria, considering behaviours regarding to
forgetfulness, carelessness as to time of administration, cessation or
discontinuation of use and replication of dose. Data were collected in
dichotomous and Likert scales. Reliability was assessed by Cronbach's alpha and
by the contribution of each item to total. The concurrent validation was done
with pill count and concordance between measures of adherence by coefficient of
Kappa. Sensitivity, specificity and accuracy were also determined. RESULTS: A
total of 135 patients were enrolled in the study. Adherence ranged from 63.8 to
72.7% in both psychometric measures and pill count. The responses on the Likert
scale showed higher proportion of non-adherence behaviour, greater variance and
concordance with pill count, as well as more sensitive to characterize the
behaviour of self-medication. The internal consistency of questionnaire was
moderate. Significant correlations were seen with items regarding the forgiveness
or careless in taking pills in all scales. The agreement between psychometric
measures and pill count was considered satisfactory. The non-adherence to malaria
therapy in an endemic area of Amazon basin was 33.3%. CONCLUSION: The five-item
reported questionnaire with responses on Likert scale is a feasible option for
reliable estimation of adherence to malaria therapy in endemic areas.
PMID- 25127887
TI - A multicenter, randomized, open-labeled study to steer immunosuppressive and
antiviral therapy by measurement of virus (CMV, ADV, HSV)-specific T cells in
addition to determination of trough levels of immunosuppressants in pediatric
kidney allograft recipients (IVIST01-trial): study protocol for a randomized
controlled trial.
AB - BACKGROUND: After kidney transplantation, immunosuppressive therapy causes
impaired cellular immune defense leading to an increased risk of viral
complications. Trough level monitoring of immunosuppressants is insufficient to
estimate the individual intensity of immunosuppression. We have already shown
that virus-specific T cells (Tvis) correlate with control of virus replication as
well as with the intensity of immunosuppression. The multicentre IVIST01-trial
should prove that additional steering of immunosuppressive and antiviral therapy
by Tvis levels leads to better graft function by avoidance of over
immunosuppression (for example, viral infections) and drug toxicity (for example,
nephrotoxicity). METHODS/DESIGN: The IVIST-trial starts 4 weeks after
transplantation. Sixty-four pediatric kidney recipients are randomized either to
a non-intervention group that is only treated conservatively or to an
intervention group with additional monitoring by Tvis. The randomization is
stratified by centre and cytomegalovirus (CMV) prophylaxis. In both groups the
immunosuppressive medication (cyclosporine A and everolimus) is adopted in the
same target range of trough levels. In the non-intervention group the
immunosuppressive therapy (cyclosporine A and everolimus) is only steered by
classical trough level monitoring and the antiviral therapy of a CMV infection is
performed according to a standard protocol. In contrast, in the intervention
group the dose of immunosuppressants is individually adopted according to Tvis
levels as a direct measure of the intensity of immunosuppression in addition to
classical trough level monitoring. In case of CMV infection or reactivation the
antiviral management is based on the individual CMV-specific immune defense
assessed by the CMV-Tvis level. Primary endpoint of the study is the glomerular
filtration rate 2 years after transplantation; secondary endpoints are the number
and severity of viral infections and the incidence of side effects of
immunosuppressive and antiviral drugs. DISCUSSION: This IVIST01-trial will answer
the question whether the new concept of steering immunosuppressive and antiviral
therapy by Tvis levels leads to better future graft function. In terms of an
effect-related drug monitoring, the study design aims to realize a
personalization of immunosuppressive and antiviral management after
transplantation. Based on the IVIST01-trial, immunomonitoring by Tvis might be
incorporated into routine care after kidney transplantation. TRIAL REGISTRATION:
EudraCT No: 2009-012436-32, ISRCTN89806912 (17 June 2009).
PMID- 25127888
TI - In silico analysis identifies novel restriction enzyme combinations that expand
reduced representation bisulfite sequencing CpG coverage.
AB - BACKGROUND: Epigenetics is the study of gene expression changes that are not
caused by changes in the deoxyribonucleic acid (DNA) sequence. DNA methylation is
an epigenetic mark occurring in C-phosphate-G sites (CpGs) that leads to local or
regional gene expression changes. Reduced-representation bisulfite sequencing
(RRBS) is a technique that is used to ascertain the DNA methylation of millions
of CpGs at single-nucleotide resolution. The genomic coverage of RRBS is given by
the restriction enzyme combination used during the library preparation and the
throughput capacity of the next-generation sequencer, which is used to read the
generated libraries. The four-nucleotide cutters, MspI and TaqalphaI, are
restriction enzymes commonly used in RRBS that, when combined, achieve ~12%
genomic coverage. The increase in throughput of next-generation sequencers allows
for novel combinations of restriction enzymes that provide higher CpG coverage.
RESULTS: We performed a near-neighbor analysis of the four nucleotide sequences
most frequently found within 50 nt of all genomic CpGs. This resulted in the
identification of seven methylation-insensitive restriction enzymes (AluI, BfaI,
HaeIII, HpyCH4V, MluCI, MseI, and MspI) that shared similar restriction
conditions suitable for RRBS library preparation. We report that the use of two
or three enzyme combinations increases the theoretical epigenome coverage to
almost half of the human genome. CONCLUSIONS: We provide the enzyme combinations
that are more likely to increase the CpG coverage in human, rat, and mouse
genomes.
PMID- 25127889
TI - SPARQLGraph: a web-based platform for graphically querying biological Semantic
Web databases.
AB - BACKGROUND: Semantic Web has established itself as a framework for using and
sharing data across applications and database boundaries. Here, we present a web
based platform for querying biological Semantic Web databases in a graphical way.
RESULTS: SPARQLGraph offers an intuitive drag & drop query builder, which
converts the visual graph into a query and executes it on a public endpoint. The
tool integrates several publicly available Semantic Web databases, including the
databases of the just recently released EBI RDF platform. Furthermore, it
provides several predefined template queries for answering biological questions.
Users can easily create and save new query graphs, which can also be shared with
other researchers. CONCLUSIONS: This new graphical way of creating queries for
biological Semantic Web databases considerably facilitates usability as it
removes the requirement of knowing specific query languages and database
structures. The system is freely available at http://sparqlgraph.i-med.ac.at.
PMID- 25127890
TI - Immigrants' use of primary health care services for mental health problems.
AB - BACKGROUND: Equity in health care across all social groups is a major goal in
health care policy. Immigrants may experience more mental health problems than
natives, but we do not know the extent to which they seek help from primary
health care services. This study aimed to determine a) the rate immigrants use
primary health care services for mental health problems compared with Norwegians
and b) the association between length of stay, reason for immigration and service
use among immigrants. METHODS: National register data covering all residents in
Norway and all consultations with primary health care services were used. We
conducted logistic regression analyses to compare Norwegians' with Polish,
Swedish, German, Pakistani and Iraqi immigrants' odds of having had a
consultation for a mental health problem (P-consultation). RESULTS: After
accounting for background variables, all immigrants groups, except Iraqi men had
lower odds of a P-consultation than their Norwegian counterparts. A shorter
length of stay was associated with lower odds of a P-consultation. CONCLUSIONS:
Service use varies by country of origin and patterns are different for men and
women. There was some evidence of a possible 'healthy migrant worker' effect
among the European groups. Together with previous research, our findings however,
suggest that Iraqi women and Pakistanis in particular, may experience barriers in
accessing care for mental health problems.
PMID- 25127893
TI - A novel sonochemical synthesis of antlerite nanorods.
AB - Antlerite - Cu3(OH)4SO4 was prepared, for the first time, by the sonochemical
method from an aqueous solution of CuSO4, without any additives. The source of
OH(-) is a result of protonation of SO4(2-) forming HSO4(-) and OH(-). The
extreme local conditions inside the cavity that are developed during the bubble
collapse (pressure is above 1000atm and the temperature is higher than 5000K)
lead to the formation of the crystalline mineral. A suggested mechanism for the
mineral formation is proposed. Due to the collapse of the bubbles, the distances
between the opposite charge Cu(2+) and SO4(2-) ions is shortened and a
crystallization process is initiated. In addition, the reaction is a one-step
process with short irradiation time of less than 30min. The chemo-physical
analysis of the sonochemically obtained product has revealed the presence of
single phase antlerite nanorods.
PMID- 25127891
TI - Comparative effectiveness of approved first-line anti-angiogenic and molecularly
targeted therapeutic agents in the treatment of good and intermediate risk
metastatic clear cell renal cell carcinoma.
AB - BACKGROUND: Based on improved clinical outcomes in randomized controlled clinical
trials (RCTs) the FDA and EMA have approved bevacizumab with interferon,
sunitinib, and pazopanib in the first-line treatment of low to intermediate risk
metastatic clear cell renal cell carcinoma (mRCC). However, there is little
comparative data to help in choosing the most effective drug among these agents.
METHODS: We performed an indirect comparative effectiveness analysis of the
pivotal RCTs of bevacizumab with interferon, sunitinib, or pazopanib compared to
one another or interferon alone in first-line treatment of metastatic or advanced
RCC. Endpoints of interest were overall survival (OS), progression free survival
(PFS), and response rate (RR). Adverse events were also examined. RESULTS: The
meta-estimate of the hazard ratio (95% confidence interval) for OS for
bevacizumab with interferon vs. interferon alone was 0.86 (0.76-0.97), for
sunitinib vs. interferon alone was 0.82 (0.67-1.00), for pazopanib vs. interferon
alone was 0.74 (0.57-0.97), for sunitinib vs. bevacizumab with interferon was
0.95 (0.75-1.20), for pazopanib vs. bevacizumab with interferon was 0.86 (0.64
1.16), and for pazopanib vs. sunitinib was 0.91 (0.76-1.08). Similarly,
bevacizumab with interferon, sunitinib, or pazopanib had better PFS and RR than
interferon alone. Sunitinib and pazopanib had better RR than bevacizumab with
interferon and there was suggestive evidence pazopanib may outperform sunitinib
in terms of RR. CONCLUSIONS: Bevacizumab with interferon, sunitinib, and
pazopanib are adequate first-line options in treatment of mRCC. Interferon alone
should not be considered an optimal first-line treatment.
PMID- 25127894
TI - [Schizophrenia and informed consent to research].
AB - CONTEXT: Informed consent to research remains a complex issue, while sometimes
staying difficult to obtain, even in the general population. This problem may be
maximized with patients suffering from schizophrenia. OBJECTIVE: This paper
summarizes available data in the literature about informed consent for research
involving patients suffering from schizophrenia. METHOD: Medline and Google
Scholar searches were conducted using the following MESH terms: schizophrenia,
informed consent and research. RESULTS: Studies using dedicated standardized
scales (e.g. MacCAT-CR) revealed a decrease in the capacity to consent of
patients with schizophrenia when compared with healthy individuals. Keeping in
mind that schizophrenia is an heterogeneous disorder, patients with the lowest
insight as well as those with the most severe cognitive symptoms appeared more
impaired in their capacity to consent. Such a poor capacity to understand and
consent to trials was shown linked with alterations in decision-making. For these
specific patients, interventions may be set up to increase their capacity to
consent. Various strategies were proposed: enhanced consent forms, extended
discussion, test/feedback method or multimedia interventions. Among them,
interventions relying on communication and the growing field of information
technologies (e.g. web-based tools) seem promising. Finally, associations
grouping families and patients (like the French Association UNAFAM) may
facilitate the involvement of patients in research programs with safer
conditions. CONCLUSION: Patients suffering from schizophrenia appear able to
consent to research programs when suitable interventions are proposed. Further
studies are now needed to optimize and individualize such interventions.
PMID- 25127892
TI - Mercury in fish and adverse reproductive outcomes: results from South Carolina.
AB - BACKGROUND: Mercury is a metal with widespread distribution in aquatic ecosystems
and significant neurodevelopmental toxicity in humans. Fish biomonitoring for
total mercury has been conducted in South Carolina (SC) since 1976, and
consumption advisories have been posted for many SC waterways. However, there is
limited information on the potential reproductive impacts of mercury due to
recreational or subsistence fish consumption. METHODS: To address this issue,
geocoded residential locations for live births from the Vital Statistics Registry
(1995-2005, N = 362,625) were linked with spatially interpolated total mercury
concentrations in fish to estimate potential mercury exposure from consumption of
locally caught fish. Generalized estimating equations were used to test the
hypothesis that risk of low birth weight (LBW, <2,500 grams) or preterm birth
(PTB, < 37 weeks clinical gestation) was greater among women living in areas with
elevated total mercury in fish, after adjustment for confounding. Separate
analyses estimated term LBW and PTB risks using residential proximity to rivers
with fish consumption advisories to characterize exposure. RESULTS: Term LBW was
more likely among women residing in areas in the upper quartile of predicted
total mercury in fish (odds ratio [OR] = 1.04; 95% confidence interval [CI]: 1.00
1.09) or within 8 kilometers of a river with a 'do not eat' fish advisory (1.05;
1.00-1.11) compared to the lowest quartile, or rivers without fish consumption
restrictions, respectively. When stratified by race, risks for term LBW or PTB
were 10-18% more likely among African-American (AA) mothers living in areas with
the highest total fish mercury concentrations. CONCLUSIONS: To our knowledge,
this is the first study to examine the relationship between fish total mercury
concentrations and adverse reproductive outcomes in a large population-based
sample that included AA women. The ecologic nature of exposure assessment in this
study precludes causal inference. However, the results suggest a need for more
detailed investigations to characterize patterns of local fish consumption and
potential dose-response relationships between mercury exposure and adverse
reproductive outcomes, particularly among AA mothers.
PMID- 25127895
TI - [Assessment of mental states at risk of psychotic transition: validation of the
French version of the CAARMS].
AB - This article aims to present the validation study of the French version of the
Comprehensive Assessment of at risk mental states (CAARMS), an interview that
seeks to determine whether young adults criteria for at-risk (AR) mental states,
or psychosis. We assessed 40 young subjects, 15 were considered as "prodromal"
(Prd) and 10 as experiencing a first episode of psychosis (PEP) by our expert
clinician at the center - centre d'evaluation des jeunes adultes et adolescents,
University Hospital Centre, Paris - and 15 were healthy controls matched for age
and sex. When assessed with the CAARMS, 73 % (n=11) of the prodromal subjects
reached the criteria for AR mental state, four subjects did not reach the
criteria for AR, nor psychosis (P) and 100 % of the PEP reached the criteria for
P. The three groups were significantly different on CAARMS total score (P<0.001)
and subscores ; Prd subjects had intermediate scores between PEP (P<0.001) and
controls (P<0.001) scores, PEP showing the highest scores. Post-hoc analysis
showed that Prd significantly differed from Controls on each subscale (P<0.001)
and that Prd differed from PEP on the "positive symptoms" subscale (P<0.001), as
well as on "behavioural change" (P=0.021), owing to difference on the item
"impaired role function". We used the brief psychiatric rating scale 24 items
with anchor (BPRS24-EA) in addition to with the CAARMS, the AR group showed
intermediate scores between controls and P subjects. Total scores of both scales
were correlated (r=0.408 ; P=0.043) and the BPRS24-EA "positive symptoms" score
was correlated with CAARMS' scores on the "Positive symptoms" subscale (r=0.456,
P=0.022), "emotional disturbance" (r=0.506, P=0.01), and "behavioural change"
(r=0.666 P=0.001). We found no correlation between BPRS negative and depression
subscales and any of the CAARMS' subscales. When looking at its reliability,
reliability coefficients (Cronbach's alpha) showed excellent reliability for
"positive symptoms", "emotional disturbance", "behavioural change" and "general
psychopathology" (respectively r=0.82, 0.75, 0.78, 0.84, 0.83) and moderate
reliability for "cognitive change", "negative symptoms" and "motor/physical
change" (respectively r=0.39, 0.59, 0.43). Overall, analysis of the results of
construct validity, concurrent validity and reliability of the CAARMS indicates
that the French version is valid and reliable. It is now available to develop and
implement early detection programs in French speaking countries.
PMID- 25127896
TI - [Clinical presentation of Moroccan cases with Alzheimer's disease].
AB - INTRODUCTION: The diagnostic approach for Alzheimer's disease is based on the
presence of cerebral atrophy combined with the score of the mini-examination of
the mental state. In this context, this study was conducted to assess the
correlation between imaging and neuropsychological testing for cases of early
onset and late-onset Alzheimer's disease. AIM OF THE STUDY: Analysis of the
clinical and paraclinical aspects of Moroccan cases with Alzheimer's disease.
METHODS: Seventeen sporadic cases and 8 family cases were seen at the memory
clinic of the Neurology Department of the University of Casablanca Ibn Rochd
Hospital. A family history was obtained through a clinical interview of the
patient and a yes or no self-reporting questionnaire from the guardian or other
family member. The disease was considered familial if at least one additional
first degree relative suffered from early-onset AD-type dementia. All patients
underwent standard somatic neurological examination, cognitive function
assessment, brain imaging and laboratory tests. Written consent was obtained from
the patients and their guardians prior to the study. RESULTS: In our study of 25
individuals, the observed mean age of AD patients was 64.52 +/- 9.30 and we
observed a slight female predominance (56% versus 44%). In addition, we found a
prevalence of AD of approximately 20%, increasing with age, in the population
below 60 years of age. Approximately half of our patients (48%) had a score lower
than 10 and were affected by severe insanity, while 28% were affected by moderate
severe insanity and 24% were light to moderately insane. Twenty-five patients
underwent neuroimaging, 18 of whom were assessed by MRI, while 7 were assessed by
CT. All patients had hippocampal atrophy, which progressed to affect others brain
regions. The blood tests showed no abnormalities in the 25 enrolled AD cases.
DISCUSSION: Age is undoubtedly the main risk factor for AD; this is also the true
for our cases where advanced age was responsible for the exponential increase of
the disease's frequency; it reached a peak in the age group of 60-69 years. The
AD diagnosis approach is based on the presence of cerebral atrophy combined with
the score of the mini-examination of the mental state (MMSE). In our study, in
addition to the MMSE, depending on the level of education, the clinician used
other tests that do not necessarily require a level of education such as the
BEC96, visual short-term or digital memory assessment, work memory assessment,
language assessment test (DO80) and apraxia. Neuropsychological examination of
the cases with a score of less than 10 showed severe cognitive impairment. The
cases presented memory and language impairments, aphasia, visual spatial
disorientation, decreased autonomy, executive dysfunction and praxis deficits,
all major causes of severe dementia. Neuroimaging revealed hippocampal and
cortical atrophy. Correlated with the other studies that aimed to establish links
between brain alterations and neuropsychological disorders, we can conclude that
a higher level of atrophy reflects a decrease in neuropsychological performance.
PMID- 25127897
TI - [Epigenetics of schizophrenia: a review].
AB - BACKGROUND: Schizophrenia is a frequent and disabling disease associated with
heterogeneous psychiatric phenotypes. It emerges during childhood, adolescence or
young adulthood and has dramatic consequences for the affected individuals,
causing considerable familial and social burden, as well as increasing health
expenses. Although some progress has been made in the understanding of their
physiopathology, many questions remain unsolved, and the disease is still poorly
understood. The prevailing hypothesis regarding psychotic disorders proposes that
a combination of genetic and/or environmental factors, during critical periods of
brain development increases the risk for these illnesses. Epigenetic regulations,
such as DNA methylation, can mediate gene x environment interactions at the level
of the genome and may provide a potential substrate to explain the variability in
symptom severity and family heritability. Initially, epigenetics was used to
design mitotic and meiotic changes in gene transcription that could not be
attributed to genetic mutations. It referred later to changes in the epigenome
not transmitted through the germline. Thus, epigenetics refers to a wide range of
molecular mechanisms including DNA methylation of cytosine residues in CpG
dinucleotides and post-translational histone modifications. These mechanisms
alter the way the transcriptional factors bind the DNA, modulating its
expression. Prenatal and postnatal environmental factors may affect these
epigenetics factors, having responsability in long-term DNA transcription, and
influencing the development of psychiatric disorders. OBJECT: The object of this
review is to present the state of knowledge in epigenetics of schizophrenia,
outlining the most recent findings in the matter. METHODS: We did so using
Pubmed, researching words such as 'epigenetics', 'epigenetic', 'schizophrenia',
'psychosis', 'psychiatric'. This review summarizes evidences mostly for two
epigenetic mechanisms: DNA methylation and post-translational histone
modifications. RESULTS: First, in terms of epidemiology and transmission, the
theoretical model of epigenetics applies to schizophrenia. Then, most
environmental factors that have proved a link with this disease, may generate
epigenetic mechanisms. Next, mutations have been found in regions implied in
epigenetic mechanism among populations with schizophrenia. Some epigenetic
alterations in DNA regions have been previously linked with neurodevelopmental
abnormalities. In psychosis, some authors have found methylation differences in
COMT gene, in reelin gene and in some genes implicated in dopaminergic,
serotoninergic, GABAergic and glutamatergic pathways. Histone modifications have
been described, in particular the H3L4 histone methylation. Finally, we tried to
underline the difficulties in epigenetic research, notably in psychiatry, and the
limits in this matter. CONCLUSION: The epigenetic field may explain a lot of
questions around the physiopathology of the complex psychiatric disease that is
schizophrenia. It may be a substratum to the prevailing hypothesis of gene x
environment interaction. The research in the matter is definitely expanding. It
justifies easily the need to improve the effort in the domain to overpass some
limits inherent to the matter.
PMID- 25127898
TI - [The link between aggressive behavior and depression in adolescence. A cross
sectional study conducted in the psychiatric emergency unit at the Sainte-Anne
hospital].
AB - INTRODUCTION: The link between depression and aggressive behavior in adults has
been found in many studies. In adolescents, this relationship is still
controversial. Several studies point out that irritability is a key symptom in
adolescent depressed. Few studies have analyzed precisely the kind of aggressive
behavior. This study sets out to assess the relationship between aggressive
behavior and depressive affects in adolescents. We also pay attention in this
population to hopelessness feelings, anxiety, global functioning and the type of
aggressive behavior. METHOD: This is a descriptive and observational cross
sectional study. Data was collected from 49 successive adolescents admitted for a
24-hour evaluation in the emergency department of the Sainte-Anne psychiatric
hospital. The inclusion period was from February to April 2012, with age limits
between 15 and 18. For each patient, the clinician completed with the parents or
other caregivers the Modified Overt Aggressive Scale (MOAS) searching for
existence of aggressive behavior in the week prior to the consultation. The
population was divided into two groups: P- group when the MOAS score was < 3 and
the P+ group when the MOAS score was >= 3. The Global Assessment of Functioning
Scale and Adolescent Depression Rating Scale for clinicians (ADRSc) were also
completed. Each patient completed the self-report Buss-Perry Aggression
Questionnaire (QA), the Beck Hopelessness scale and the Adolescent Depression
Rating Scale for patients (ADRSp). RESULTS: Forty-nine adolescents with a median
age of 16 years and 4 months participated. The first reason for consultation was
depressive symptoms, followed by disruptive behavior. The analysis was conducted
on 39 questionnaires. The demographic profile of the two groups was similar. We
did not find any significant difference between the groups P+ and P- on ADRSc
scores and secondary criteria. However, we found higher scores in the QA in the
more depressed patient, especially a higher hostility score in this sample. In
the subgroup analysis: as expected self-aggressive behavior was associated with a
higher depression score, more hospitalization and a poor global functioning
score. Surprisingly, the patients who showed physical aggression against others
had a better prognosis and lower depression scores. DISCUSSION: The study did not
conclude on the link between aggressive behavior and depression in this
population. The adolescent hostility appears more characteristic of depression
compared to other dimensions of aggressivity (anger, verbal aggression, physical
aggression) in adolescents. Physical aggression against others appeared not only
less typical in depression but was also associated with a better global
functioning. Clinicians should pay particular attention to the kind of aggressive
behavior in clinical evaluations of adolescents in an emergency context.
PMID- 25127899
TI - Optimal beam arrangement for pulmonary ventilation image-guided intensity
modulated radiotherapy for lung cancer.
AB - BACKGROUND: The principal aim of this study was to evaluate the feasibility of
incorporating four-dimensional (4D)-computed tomography (CT)-based functional
information into treatment planning and to evaluate the potential benefits of
individualized beam setups to better protect lung functionality in patients with
non-small cell lung cancer (NSCLC). METHODS: Peak-exhale and peak-inhale CT scans
were carried out in 16 patients with NSCLC treated with intensity-modulated
radiotherapy (IMRT). 4D-CT-based ventilation information was generated from the
two sets of CT images using deformable image registration. Four kinds of IMRT
plans were generated for each patient: two anatomic plans without incorporation
of ventilation information, and two functional plans with ventilation
information, using either five equally spaced beams (FESB) or five manually
optimized beams (FMOB). The dosimetric parameters of the plans were compared in
terms of target and normal tissue structures, with special focus on dose
delivered to total lung and functional lung. RESULTS: In both the anatomic and
functional plans, the percentages of both the functional and total lung regions
irradiated at V5, V10, and V20 (percentage volume irradiated to >5, >10 and >20
Gy, respectively) were significantly lower for FMOB compared with FESB (P <
0.05), but there was no significant difference for V30 (P > 0.05). Compared with
FESB, a greater degree of sparing of the functional lung was achieved in
functional IMRT plans with optimal beam arrangement, without compromising target
volume coverage or the irradiated volume of organs at risk, such as the spinal
cord, esophagus, and heart. CONCLUSIONS: Pulmonary ventilation image-guided IMRT
planning with further optimization of beam arrangements improves the preservation
of functional lung in patients with NSCLC.
PMID- 25127900
TI - Therapeutic targeting of angiogenesis with a recombinant CTT peptide-endostatin
mimic-kringle 5 protein.
AB - Angiogenesis is required for tumor growth and metastasis, and targeting
angiogenesis is a novel anticancer strategy. However, cancer development is a
complex multistep process, and single antiangiogenic agents have limited
therapeutic efficacy. Here, we report a triple fusion protein, namely CTT peptide
endostatin mimic-kringle 5 (AARP), consisting of MMP-2/9-selective inhibitory
peptide (CTT peptide) and well-known endogenous antiangiogenic agents (endostatin
mimic and kringle 5), which can simultaneously target matrix metalloproteinases
(MMP) and endothelial cells, blocking their actions. AARP was bacterially
expressed, and biologic activity of purified AARP was assessed. AARP could
significantly inhibit the enzymatic activity of MMP-2/9, proliferation,
migration, and tube formation of endothelial cells in vitro. The antitumor
activity of AARP was shown in a concentration-dependent manner when injected i.p.
into immunodeficient mice bearing multidrug-resistant human epidermoid carcinomas
(KB), and AARP is superior to clinical grade endostatin in inhibiting KB
xenograft growth. In mouse models of Lewis lung carcinoma (LLC) and hepatoma H22,
when given as a single dose, AARP is highly effective for reducing tumor growth,
angiogenesis, and metastasis, and increasing survival time. AARP possessed
significantly greater antiangiogenic activity than endostatin mimic, CTT peptide
kringle 5 (RK5) both in vitro and in vivo. Compared with conventional
chemotherapeutic agents (cyclophosphamide and paclitaxel), AARP is also
effective. More importantly, AARP is cytocompatible and no tissue toxicity could
be observed after large dose administration. Taken together, our findings suggest
AARP is a highly effective, safe, and more potent antiangiogenic agent for
blocking tumor angiogenesis and metastasis, and warrants further testing for
clinical applications.
PMID- 25127902
TI - Over-testing for heparin induced thrombocytopenia in hospitalized patients.
AB - Heparin induced thrombocytopenia (HIT) is a pro-thrombotic and potentially fatal
complication of heparin therapy. Its diagnosis rests on high clinical probability
and the laboratory demonstration of anti-PF4/heparin antibodies. The high
prevalence of thrombocytopenia in hospitalized patients and the high sensitivity
but low specificity of immunoassays for HIT antibodies can lead to over-testing
and over-diagnosis. We conducted a study to review HIT screening practices in a
tertiary care setting. We reviewed 63 consecutive patients undergoing testing for
anti-PF4/heparin antibodies over 3 months. Pre-test probability for HIT was
calculated using the 4T score. Sixty three patients underwent testing for anti
PF4/heparin antibodies. Twenty one had been admitted for cardiovascular surgery,
5 for other surgery and 35 for non-surgical indications. Twenty nine patients (46
%) had low pre- test probability, twenty three (36.5 %) had intermediate
probability, and eleven (17.4 %) had high pre-test probability of having HIT.
Anti-PF4/heparin ELISA was positive in 8 of 63 patients. SRA was ordered for 16
patients and was positive in 5. Only five patients were diagnosed and treated for
HIT. Over-testing for HIT is highly prevalent in a tertiary care setting. This
increases cost and exposes patients to expensive anti-coagulation with its
attendant risk of hemorrhage. The 4Ts score has been shown to have high
sensitivity and may be used to rule out HIT in most situations, although its
utility depends on subjective analysis. Consistently applying this in practice
could minimize over-testing and facilitate safer, cost-effective care.
PMID- 25127903
TI - Thromboelastography defines late hypercoagulability after TBI: a pilot study.
AB - INTRODUCTION: Traumatic brain injury (TBI) is associated with a hypercoagulable
state, the mechanism and duration of which remain unclear. We sought to determine
whether thromboelastography (TEG) analysis could identify the hypercoagulable
state after TBI, as defined by elevations in maximal amplitude (MA), thrombus
generation (TG), G value (G), and alpha angle (alphaA). METHODS: Patients with
moderate-severe TBI, defined primarily as a GCS <12, admitted between 1/2012 and
8/2013 were eligible for enrolment in this prospective cohort study. TEG profiles
were obtained between 0-24 h (T1), 24-48 h (T2), 48-72 h (T3), 72-96 h (T4), and
96-120 h (T5) after admission. Early TEG was defined as 0-48 h, and late TEG was
defined as >48 h. RESULTS: Twenty five patients (80 % men) and 7 age- and sex
matched control subjects were studied. Median age was 38 years (range 18-85).
Early MA was [63.6 mm (60.5, 67.4)] versus late MA [69.9 mm (65.2,73.9); p =
0.02], early TG was [763.3 mm/min (712.8, 816.2)] versus late TG [835.9 mm/min
(791.2,888.3); p = 0.02], and early G was [8.8 d/cm(2) (7.7,10.4)] versus late G
[11.6 d/cm(2) (9.4,14.1); p = 0.02]. Study patients had higher MA (p = 0.02), TG
(p = 0.03), and G (p = 0.02) values at T5 compared to controls. There was a
linear increase per day of MA by 2.6 mm (p = 0.001), TG 31.9 mm/min (p <= 0.001),
and G value by 1.3 d/cm(2) (p <= 0.001) when clustered by pairs in regression
analysis. Lower MA values trended toward home discharge (p = 0.08). CONCLUSION:
The data suggest a progressive and delayed hypercoagulable state observed days
after initial TBI. The hypercoagulable state may reflect excess platelet
activity.
PMID- 25127904
TI - Risk of reintubation in neurosurgical patients.
AB - BACKGROUND: Reintubation among neurosurgical patients is poorly characterized.
The aim of this study was to delineate the rate of reintubation among
neurosurgical patients. In addition, we seek to characterize the patient
demographic features, comorbidities, and surgical characteristics that may be
associated with reintubation among neurosurgical patients. METHODS: This is a
retrospective cohort study conducted in the setting of hospitals participating in
the American College of Surgeons' National Surgical Quality Improvement Program
between 2005 and 2010. All adult patients undergoing neurosurgery under general
anesthesia were included. Exclusion criteria were preoperative mechanical
ventilation or pneumonia prior to surgery. Reintubation was defined as placement
of an endotracheal tube or mechanical ventilation within 48 h after surgery.
RESULTS: Among 17,483 eligible patients, 74 (0.42 %; 95 % CI 0.33-0.52 %)
required reintubation within 48 h of surgery. In multiple logistic regression,
the following were associated with increased risk of reintubation: age >65 years
(OR 2.1; 95 % CI 1.3-3.4), preoperative renal failure (OR 2.9; 95 % CI 1.0-8.5),
quadriplegia (OR 8.2; 95 % CI 3.3-20.3), COPD (OR 2.1; 95 % CI 1.0-4.3),
operative time >3 h (OR 2.9; 95 % CI 1.8-4.8), and higher ASA class (OR per
point, 2.1; 95 % CI 1.4-3.1). Spinal surgery was found to be protective relative
to cranial neurosurgery or endarterectomy (OR 0.3; 95 % CI 0.2-0.5). CONCLUSIONS:
Reintubation after neurosurgery is associated with older patients with a greater
number of comorbidities. In particular, renal, pulmonary, and severe neurologic
comorbidities; longer operative duration; and cranial, rather than spinal,
pathology were associated with increased risk for reintubation. These findings
may be helpful in triage decisions regarding postoperative intensity of care and
monitoring.
PMID- 25127905
TI - Long-term outcome and quality of life after craniectomy in speech-dominant
swollen middle cerebral artery infarction.
AB - BACKGROUND: Decompressive craniectomy in malignant middle cerebral artery
infarction (MMCAI) reduces mortality. Whether speech-dominant side infarction
results in less favorable outcome is unclear. This study compared functional
outcome, quality of life, and mental health among patients with speech-dominant
and non-dominant side infarction. METHODS: All patients undergoing decompressive
craniectomy for MMCAI were included. Demographics, side of infarction, and speech
dominant hemisphere were recorded. Outcome at follow-up was assessed by global
functioning (modified Rankin Scale score), neurological impairment (National
Institutes of Health Stroke Scale score), dependency (Barthel Index), anxiety and
depression (Hospital Anxiety and Depression scale), and quality of life (Short
Form-36). RESULTS: Twenty-nine out of 45 patients (mean age +/- SD, 48.1 +/- 11.6
years; 58 % male) were alive at follow-up, and 26 were eligible for analysis
[follow-up, median (interquartile range): 66 months (32-93)]. The speech-dominant
hemisphere was affected in 13 patients. Outcome for patients with speech-dominant
and non-dominant side MMCAI was similar regarding neurological impairment
(National Institutes of Health Stroke Scale score, mean +/- SD: 10.3 +/- 7.0 vs.
8.9 +/- 2.7, respectively; p = 0.51), global functioning [modified Rankin Scale
score, median (IQR): 3.0 [2-4] vs. 4.0 [3-4]; p = 0.34], dependence (Barthel
Index, mean +/- SD: 16.2 +/- 5.0 vs. 13.1 +/- 4.8; p = 0.12), and anxiety and
depression (Hospital Anxiety and Depression scale, mean +/- SD: anxiety, 5.0 +/-
4.5 vs. 7.3 +/- 5.8; p = 0.30; depression, 5.0 +/- 5.2 vs. 5.9 +/- 3.9; p =
0.62). The mean quality of life scores (Short Form-36) were not significantly
different between the groups. CONCLUSIONS: There was no statistical or clinical
difference in functional outcome and quality of life in patients with speech
dominant compared to non-dominant side infarction. The side affected should not
influence suitability for decompressive craniectomy.
PMID- 25127906
TI - Characterizing Influenza surveillance systems performance: application of a
Bayesian hierarchical statistical model to Hong Kong surveillance data.
AB - BACKGROUND: Infectious disease surveillance is a process the product of which
reflects both actual disease trends and public awareness of the disease.
Decisions made by patients, health care providers, and public health
professionals about seeking and providing health care and about reporting cases
to health authorities are all influenced by the information environment, which
changes constantly. Biases are therefore imbedded in surveillance systems; these
biases need to be characterized to provide better situational awareness for
decision-making purposes. Our goal is to develop a statistical framework to
characterize influenza surveillance systems, particularly their correlation with
the information environment. METHODS: We identified Hong Kong influenza
surveillance data systems covering healthcare providers, laboratories, daycare
centers and residential care homes for the elderly. A Bayesian hierarchical
statistical model was developed to examine the statistical relationships between
the influenza surveillance data and the information environment represented by
alerts from HealthMap and web queries from Google. Different models were fitted
for non-pandemic and pandemic periods and model goodness-of-fit was assessed
using common model selection procedures. RESULTS: Some surveillance systems -
especially ad hoc systems developed in response to the pandemic flu outbreak -
are more correlated with the information environment than others. General
practitioner (percentage of influenza-like-illness related patient visits among
all patient visits) and laboratory (percentage of specimen tested positive) seem
to proportionally reflect the actual disease trends and are less representative
of the information environment. Surveillance systems using influenza-specific
code for reporting tend to reflect biases of both healthcare seekers and
providers. CONCLUSIONS: This study shows certain influenza surveillance systems
are less correlated with the information environment than others, and therefore,
might represent more reliable indicators of disease activity in future outbreaks.
Although the patterns identified in this study might change in future outbreaks,
the potential susceptibility of surveillance data is likely to persist in the
future, and should be considered when interpreting surveillance data.
PMID- 25127907
TI - The effect of transforming growth factor beta1 on the crosstalk between autophagy
and apoptosis in the annulus fibrosus cells under serum deprivation.
AB - Autophagy and apoptosis are important in maintaining the metabolic homeostasis of
intervertebral disc cells, and transforming growth factor-beta1 (TGF-beta1) is
able to delay intervertebral disc degeneration. This study determined the effect
of TGF-beta1 on the crosstalk between autophagy and apoptosis in the disc cells,
with the aim to provide molecular mechanism support for the prevention and
treatment of disc degeneration. Annulus fibrosus (AF) cells were isolated and
cultured under serum starvation. 10 ng/mL TGF-beta1 reduced the apoptosis
incidence in the cells under serum starvation for 48 h, down-regulated the
autophagy incidence in the cells pretreated with 3-methyladenine (3-MA) or
Bafilomycin A (Baf A), partly rescued the increased apoptosis incidence in the
cells pretreated with 3-MA, while further reduced the decreased apoptosis
incidence in the cells pretreated with Baf A. Meanwhile, TGF-beta1 down-regulated
the expressions of autophagic and apoptotic markers in the cells under
starvation, partly down-regulated the expressions of Beclin-1, LC3 II/I and
cleaved caspase-3 in the cells pretreated with 3-MA or Baf A, while significantly
decreased the expression of Bax/Bcl-2 in the cells pretreated with Baf A. 3-MA
blocked the phosphorylation of both AKT and mTOR and partly reduced the
inhibitory effect of TGF-beta1 on the expression of LC3 II/I and cleaved caspase
3. TGF-beta1 enhanced the expression of p-ERK1/2 and down-regulated the
expressions of LC3 II/I and cleaved caspase-3. U0126 partly reversed this
inhibitory effect of TGF-beta1. In conclusion, TGF-beta1 protected against
apoptosis of AF cells under starvation through down-regulating excessive
autophagy. PI3K-AKT-mTOR and MAPK-ERK1/2 were the possible signaling pathways
involved in this process.
PMID- 25127908
TI - Delayed versus early motion after arthroscopic rotator cuff repair: a meta
analysis.
AB - BACKGROUND: We conducted a meta-analysis of randomized trials to compare delayed
vs early motion therapy on function after arthroscopic rotator cuff repair.
METHODS: We searched 4 electronic databases (Medline, Embase, Cochrane, and
Physiotherapy Evidence Database [PEDro]). The methodologic quality of the
included studies was assessed, and the relevant data were extracted. Data were
pooled for functional outcomes, rotator cuff tear recurrence, and shoulder range
of motion. Complications were reported descriptively. RESULTS: Three level I and
1 level II randomized trials were eligible and included. Pooled analysis revealed
no statistically significant differences in American Shoulder and Elbow Surgeons
scores between delayed vs early motion rehabilitation (mean difference [MD], 1.4;
95% confidence interval [CI], -1.8 to 4.7; P = .38, I(2) = 34%). The risk of
retears after surgery did not differ statistically between treatment groups (risk
ratio, 1.01; 95% CI, 0.63-1.64; P = .95). Early passive motion led to a
statistically significant, although clinically unimportant, improvement in
forward elevation between groups (MD, -1 degrees ; 95% CI, -2 degrees to 0
degrees ; P = 0.04, I(2) = 0%). There was no difference in external rotation
between treatment groups (MD, 1 degrees ; 95% CI, -2 degrees to 4 degrees ; P =
0.63, I(2) = 0%). None of the included studies identified any cases of
postoperative shoulder stiffness. CONCLUSIONS: The current meta-analysis did not
identify any significant differences in functional outcomes and relative risks of
recurrent tears between delayed and early motion in patients undergoing
arthroscopic rotator cuff repairs. A statistically significant difference in
forward elevation range of motion was identified; however, this difference is
likely clinically unimportant.
PMID- 25127909
TI - A preoperative scoring system to select patients for arthroscopic subacromial
decompression.
AB - BACKGROUND: This study investigated the clinical and radiographic factors that
influence outcome after arthroscopic subacromial decompression (ASAD) for
shoulder impingement syndrome. The goal was to develop a new preoperative scoring
system to identify patients who would have a prompt and sustained benefit from
ASAD. METHODS: We prospectively reviewed 112 consecutive patients with
impingement syndrome who subsequently underwent ASAD. The Oxford Shoulder Score
(OSS) was recorded preoperatively and 3 and 12 months postoperatively. A
statistically significant improvement in OSS at 3 months after surgery was
considered a good outcome. RESULTS: The variables associated with good outcome
were shoulder pain with overhead activities, persistent symptoms for more than 6
months, symptoms persistent despite a 3-month course of supervised physiotherapy,
consistently positive Hawkins test result, radiologic changes of impingement on
both acromion and humerus in the subacromial region, and improvement for more
than 1 week after a steroid injection. These 6 criteria were combined into a
single score for this study, termed the preoperative score (PrOS). Sixty-two
patients who had been symptomatic for 1 year with a preoperative score of 5 to 6
showed significant improvement in OSS at 3 months after surgery (P < .001).
Thirty-eight patients with a score 3 to 4 had no statistically significant
improvement in OSS at 3 months but had a further slight improvement at 1 year.
Twelve patients with a score of <=2 had no significant improvement in OSS at 3
months or 1 year. CONCLUSION: This scoring system can identify patients who would
have a prompt benefit from ASAD. The impact of surgery in patients with a PrOS of
<=4 points is questionable.
PMID- 25127910
TI - Case report: misdiagnosed olecranon bursitis: pyoderma gangrenosum.
PMID- 25127911
TI - Successful treatment of humeral giant aneurysmal bone cyst: value of the induced
membrane reconstruction technique.
PMID- 25127912
TI - Arthroscopic repair of an avulsed latissimus dorsi tendon transfer for massive,
irreparable rotator cuff tear: a report of two cases.
PMID- 25127913
TI - Regarding "meta-analysis comparing single-row and double-row repair techniques in
the arthroscopic treatment of rotator cuff tears".
PMID- 25127914
TI - Response to "meta-analysis comparing single-row and double-row repair techniques
in the arthroscopic treatment of rotator cuff tears".
PMID- 25127915
TI - Effect of a medical toxicology admitting service on length of stay, cost, and
mortality among inpatients discharged with poisoning-related diagnoses.
AB - There are no published studies that have compared quality outcomes of
hospitalized poisoned patients primarily under the care of physician medical
toxicologists to patients treated by non-toxicologists. We hypothesized that
inpatients primarily cared for by medical toxicologists would exhibit shorter
lengths of stay (LOS), lower costs, and decreased mortality. Patients discharged
in 2010 and 2011 from seven hospitals within the same health care system and
greater metropolitan area with Medicare severity diagnosis-related groups for
"poisoning and toxic effects of drugs" with and without major comorbidities or
complications (917 & 918, respectively) were identified from a Premier(r)
database. The database contained severity-weighted comparisons between expected
and observed outcomes for each patient. Outcome parameters were differences
between expected and observed LOS, cost, and percent mortality. These were then
compared among groups of patients primarily admitted and cared for by (1) medical
toxicologists at one hospital (Banner Good Samaritan Medical Center, BGS), (2)
non-toxicologists at BGS, and (3) non-toxicologists at six other hospitals.
Records of 3,581 patients contained complete data for assessment of at least one
outcome measure. Patients cared for by medical toxicologists experienced
favorable differences in LOS, costs, and mortality compared with other patient
groups (p < 0.001). If patients cared for by non-toxicologists had experienced
similar differences in observed over expected values for LOS, cost, and mortality
as those cared for by medical toxicologists, there would have been a median
savings of 1,483 hospital days, $4.269 million, and a significant decrease in
mortality during the 2-year study period. Differences between observed and
expected LOS, cost, and mortality in patients primarily cared for by medical
toxicologists were significantly better than in patients cared for by non
toxicologists, regardless of facility. These data suggest that significant
reductions in patient hospital days, costs, and mortality are possible when
medical toxicologists directly care for hospitalized patients.
PMID- 25127917
TI - The diagnosis of febrile urinary tract infection in children may be facilitated
by urinary biomarkers.
AB - BACKGROUND: We prospectively assessed the feasibility of two urinary markers of
renal injury as potential diagnostic tests for acute febrile urinary tract
infection (UTI) and subsequent renal scarring. METHODS: The patient cohort
comprised children aged 0 to 4 years who visited the emergency room. The children
were divided into three groups, namely, a febrile UTI (fUTI), febrile control
(FC) and a non-febrile control (NFC) group, respectively, which were matched for
sex and age. An enzyme-linked immunosorbent assay for neutrophil gelatinase
associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) was performed on
urine collected from each child. The urine levels of both markers were compared
between the three groups, and the diagnostic accuracy was determined based on the
area under the receiver-operator characteristic curve (AUC). In the fUTI group,
the predictability of subsequent renal scarring was assessed by associating
urinary levels with dimercaptosuccinic acid findings 6 months after an UTI
episode. RESULTS: Significantly elevated levels of urinary NGAL and KIM-1 were
observed in the fUTI group, as well as with increased urine esterase, serum C
reactive protein, and pyuria. The AUC was 72 % for KIM-1 and 96 % for NGAL. The
AUC of KIM-1 for the prediction of scarring was 71 % (p < 0.05). CONCLUSIONS: The
diagnosis of febrile UTI and the prediction of subsequent scarring may be
facilitated by assaying urine biomarkers with acceptable accuracy.
PMID- 25127918
TI - Salt intake in children and its consequences on blood pressure.
AB - Sodium is the most abundant extracellular cation and therefore pivotal in
determining fluid balance. At the beginning of life, a positive sodium balance is
needed to grow. Newborns and preterm infants tend to lose sodium via their
kidneys and therefore need adequate sodium intake. Among older children and
adults, however, excessive salt intake leads to volume expansion and arterial
hypertension. Children who are overweight, born preterm, or small for gestational
age and African American children are at increased risk of developing high blood
pressure due to a high salt intake because they are more likely to be salt
sensitive. In the developed world, salt intake is generally above the recommended
intake also among children. Although a positive sodium balance is needed for
growth during the first year of life, in older children, a sodium-poor diet seems
to have the same cardiovascular protective effects as among adults. This is
relevant, since: (1) a blood pressure tracking phenomenon was recognized; (2) the
development of taste preferences is important during childhood; and (3) salt
intake is often associated with the consumption of sugar-sweetened beverages
(predisposing children to weight gain).
PMID- 25127919
TI - Disturbed skin barrier in children with chronic kidney disease.
AB - BACKGROUND: There are limited data on skin lesions in children with end-stage
renal failure. The aim of the study was an evaluation of the skin barrier in
children with different stages of chronic kidney disease (CKD). The prevalence of
xerosis, its severity, as well as its link selected demographic factors, were
examined. METHODS: The study included 103 children: 72 with CKD stages 3-5 (38 on
conservative treatment and 34 on dialysis) and 31 patients with primary
monosymptomatic nocturnal enuresis as a control group. Initially, the study
subjects described the localisation and severity of dry skin by themselves. Next,
clinical evaluation of xerosis, non-invasive corneometric assessment of epidermis
moisturising and the measurement of transepidermal water loss were performed.
RESULTS: Most CKD children reported dry skin. The problem of xerosis was
identified more frequently in patients on dialysis (67.6 %) than on conservative
treatment (42.1 %) (p = 0.01). CKD patients divided according to skin dryness did
not differ with regards to age, sex, initial kidney disease and CKD duration.
CONCLUSIONS: Disturbed skin barrier is an important concern of children with CKD,
intensifying as the disease progresses. This symptom occurs on early stages of
CKD and it should be taken into consideration in the CKD management.
PMID- 25127920
TI - The paired box transcription factor Pax8 is essential for function and survival
of adult thyroid cells.
AB - The transcription factor Pax8 is already known to be essential at very early
stages of mouse thyroid gland development, before the onset of thyroid hormone
production. In this paper we show, using a conditional inactivation strategy,
that the removal of the Pax8 protein late in gland development results in severe
hypothyroidism, consequent to a reduced gland size and a deranged
differentiation. These results demonstrate that Pax8 is also an essential player
in controlling survival and differentiation of adult thyroid follicular cells.
PMID- 25127916
TI - Best practice guidelines for idiopathic nephrotic syndrome: recommendations
versus reality.
AB - BACKGROUND: The optimal therapeutic regimen for managing childhood idiopathic
nephrotic syndrome (INS) is still under debate. We have evaluated the choice of
steroid regimen and of symptomatic treatment adopted by pediatricians and
pediatric nephrologists in a large number of centers as the first step towards
establishing a shared protocol METHODS: This was a multicenter, retrospective
study. A total of 231 children (132 admitted to pediatric units) aged 6 months to
<15 years who presented with onset of nephrotic syndrome to 54 pediatric units
and six pediatric nephrology units in Italy between 2007 and 2009 were eligible
for entry into the study. RESULTS: Median steroid dosing was 55 (range 27-75)
mg/m(2)/day. The overall median cumulative dose regimen for the first episode was
3,440 (1,904-6,035) mg/m(2), and the median duration of the therapeutic regimen
was 21 (9-48) weeks. The total duration and cumulative steroid dose were
significantly higher in patients treated by pediatricians than in those treated
by pediatric nephrologists (p = 0.001 and p = 0.008). Among the patient cohort,
55, 64 and 22 % received albumin infusions, diuretics and acetyl salicylic acid
treatment, respectively, but the laboratory and clinical data did not differ
between children treated or not treated with symptomatic drugs. Albumin and
diuretic use did not vary between patients in pediatric units and those in
pediatric nephrology units. CONCLUSIONS: This study shows major differences in
steroid and symptomatic treatment of nephrotic syndrome by pediatricians and
pediatric nephrologists. As these differences can influence the efficacy of the
treatments and the appearance of side-effects, shared guidelines and their
implementation through widespread educational activities are necessary.
PMID- 25127921
TI - Indicators of pulmonary exacerbation in cystic fibrosis: A Delphi survey of
patients and health professionals.
AB - BACKGROUND: There is uncertainty about the most important indicators of pulmonary
exacerbations in CF. METHODS: Two parallel Delphi surveys in 13 CF centres (UK
and Ireland). Delphi 1: 31 adults with CF, >= one exacerbation over 12 months.
Delphi 2: 38 CF health professionals. Rounds 1 and 2 participants rated their
level of agreement with statements relating to indicators of exacerbation; Round
3 participants rated the importance of statements which were subsequently placed
in rank order. RESULTS: Objective measurements were of higher importance to
health professionals. Feelings of increased debility were rated most important by
adults with CF. CONCLUSIONS: There were clear differences in perspectives between
the two groups as to the most important indicators of an exacerbation. This
highlights that CF health professionals should take more cognisance of specific
signs and symptoms reported by adults with CF, especially since these may be a
precursor to an exacerbation.
PMID- 25127923
TI - Sub-aponeurotic fluid collection in a neonate associated with fetal scalp
electrode monitoring: a brief communication.
PMID- 25127922
TI - High-frequency audiometry reveals high prevalence of aminoglycoside ototoxicity
in children with cystic fibrosis.
AB - BACKGROUND: Intravenous aminoglycoside (IV AG) antibiotics, widely used in
patients with cystic fibrosis (CF), are known to have ototoxic complications.
Despite this, audiological monitoring is not commonly performed and if performed,
uses only standard pure-tone audiometry (PTA). The aim of this study was to
investigate ototoxicity in CF children, to determine the most appropriate
audiological tests and to identify possible risk factors. METHODS: Auditory
assessment was performed in CF children using standard pure tone audiometry
(PTA), extended high-frequency (EHF) audiometry and distortion-product
otoacoustic emissions (DPOAE). RESULTS: 70 CF children, mean (SD) age 10.7 (3.5)
years, were recruited. Of the 63 children who received IV AG, 15 (24%) children
had ototoxicity detected by EHF audiometry and DPOAE. Standard PTA only detected
ototoxicity in 13 children. Eleven of these children had received at least 10
courses of IV AG courses. A 25 to 85 dBHL hearing loss (mean+/-SD: 57.5+/-25.7
dBHL) across all EHF frequencies and a significant drop in DPOAE amplitudes at
frequencies 4 to 8 kHz were detected. However, standard PTA detected a
significant hearing loss (>20 dBHL) only at 8 kHz in 5 of these 15 children and
none in 2 subjects who had significantly elevated EHF thresholds. The number of
courses of IV AG received, age and lower lung function were shown to be risk
factors for ototoxicity. CONCLUSIONS: CF children who had received at least 10
courses of IV AG had a higher risk of ototoxicity. EHF audiometry identified 2
more children with ototoxicity than standard PTA and depending on facilities
available, should be the test of choice for detecting ototoxicity in children
with CF receiving IV AG.
PMID- 25127924
TI - Immunomodulation of antiretroviral drug-suppressed chronic HIV-1 infection in an
oral probiotic double-blind placebo-controlled trial.
AB - A putative source of inappropriate immune activation that drives human
immunodeficiency virus (HIV)-1 immunopathogenesis is the gastrointestinal tract.
Even with effective antiretroviral treatment, residual activation persists. We
hypothesized that an oral probiotic could improve the residual immune activation
in chronic treated HIV-1 infection, and tested a Bacillus coagulans GBI-30, 6086
capsule probiotic in HIV-1-infected persons with suppressed viremia on stable
antiretroviral therapy in a 3-month double-blind placebo-controlled trial (10
probiotic, 7 placebo). The Gastrointestinal Symptom Rating Scale (GSRS) was
administered monthly. Blood was tested at the start and end of placebo/probiotic
administration for viremia, CD4(+) T cell percentage/concentration, soluble
(s)CD14, soluble intestinal fatty acid binding protein, sCD163, D-dimer, C
reactive protein (CRP), interleukin-8, and tumor necrosis factor-alpha. All
participants maintained viremia <40 RNA copies/ml. The probiotic was safe and
well tolerated, and appeared to improve chronic gastrointestinal symptoms. Its
administration was associated with a significant increase in the percentage of
blood CD4(+) T cells compared to placebo (+2.8% versus -1.8%, p=0.018) although
CD4(+) T cell concentrations were generally unchanged in both groups. None of the
biomarkers showed significant changes on probiotic treatment or between-group
differences in change (although significance was borderline for a greater sCD163
drop in the probiotic versus placebo group, p=0.05). Some biomarkers showed
significant correlations to each other, particularly D-dimer with CRP and sCD14
with tumor necrosis factor (TNF)-alpha. These data demonstrate the safety and
possible benefit of this probiotic for residual inflammation in treated HIV-1
infection, although further study will be required to determine the immune
pathways involved.
PMID- 25127925
TI - Riluzole in the prelimbic medial prefrontal cortex attenuates veratrine-induced
anxiety-like behaviors in mice.
AB - RATIONALE: We previously demonstrated in mice that the activation of prelimbic
medial prefrontal cortex (PL) with the sodium channel activator veratrine induces
anxiety-like behaviors via NMDA receptor-mediated glutamatergic
neurotransmission. Riluzole directly affects the glutamatergic system and has
recently been suggested to have an anxiolytic-like effect in both experimental
animals and patients with anxiety disorders. OBJECTIVES: We investigated the
effects of co-perfusion of riluzole on veratrine-induced anxiety-like behaviors
in mice. METHODS: Extracellular glutamate levels were measured in 7-week-old male
C57BL6 mice by using an in vivo microdialysis-HPLC/ECD system, and behaviors were
assessed simultaneously in an open field (OF) test. Basal levels of glutamate
were measured by collecting samples every 10 min for 60 min. The medium
containing drugs was perfused for 30 min, and the OF test was performed during
the last 10 min of drug perfusion. After the drug treatments, the drug-containing
medium was switched to perfusion of control medium lacking drugs, and then
samples were collected for another 90 min. RESULTS: Riluzole co-perfusion
attenuated veratrine-induced increase in extracellular glutamate levels in the PL
and completely diminished veratrine-induced anxiety-like behaviors.
Interestingly, riluzole perfusion alone in the PL did not affect the basal levels
of glutamate and anxiety-like behaviors. CONCLUSIONS: Our results suggest that
compounds like riluzole that inhibit glutamatergic function in the PL are
possible candidates for novel anxiolytics.
PMID- 25127926
TI - ADRA2B genotype differentially modulates stress-induced neural activity in the
amygdala and hippocampus during emotional memory retrieval.
AB - RATIONALE: Noradrenaline interacts with stress hormones in the amygdala and
hippocampus to enhance emotional memory consolidation, but the noradrenergic
glucocorticoid interaction at retrieval, where stress impairs memory, is less
understood. OBJECTIVES: We used a genetic neuroimaging approach to investigate
whether a genetic variation of the noradrenergic system impacts stress-induced
neural activity in amygdala and hippocampus during recognition of emotional
memory. METHODS: This study is based on genotype-dependent reanalysis of data
from our previous publication (Li et al. Brain Imaging Behav 2014). Twenty-two
healthy male volunteers were genotyped for the ADRA2B gene encoding the alpha2B
adrenergic receptor. Ten deletion carriers and 12 noncarriers performed an
emotional face recognition task, while their brain activity was measured with
fMRI. During encoding, 50 fearful and 50 neutral faces were presented. One hour
later, they underwent either an acute stress (Trier Social Stress Test) or a
control procedure which was followed immediately by the retrieval session, where
participants had to discriminate between 100 old and 50 new faces. RESULTS: A
genotype-dependent modulation of neural activity at retrieval was found in the
bilateral amygdala and right hippocampus. Deletion carriers showed decreased
neural activity in the amygdala when recognizing emotional faces in control
condition and increased amygdala activity under stress. Noncarriers showed no
differences in emotional modulated amygdala activation under stress or control.
Instead, stress-induced increases during recognition of emotional faces were
present in the right hippocampus. CONCLUSION: The genotype-dependent effects of
acute stress on neural activity in amygdala and hippocampus provide evidence for
noradrenergic-glucocorticoid interaction in emotional memory retrieval.
PMID- 25127928
TI - Predictors of stress and coping strategies of US accelerated vs. generic
Baccalaureate Nursing students: an embedded mixed methods study.
AB - BACKGROUND: Stress is an inevitable part of life and is especially pervasive in
the lives of nursing students. Identifying the predictors of stress as well as
coping strategies used can allow for the implementation of appropriate coping
interventions to assist in the management of stress in nursing students. Mixed
methods research that has been undertaken to gain an understanding about student
stress, especially juxtaposing generic versus accelerated nursing students could
not be identified. OBJECTIVES: (1) Identify predictors of stress between
accelerated and generic Baccalaureate Nursing (BSN) students; and (2) Describe
stressors and coping strategies used by accelerated students in comparison with
generic students. DESIGN: Embedded mixed methods study. SETTING: Accelerated and
generic BSN third- and fourth-year nursing students at two Midwestern
universities. PARTICIPANTS: 210 participants: accelerated (n=75) and generic
(n=135). METHODS: A questionnaire packet, including demographics, history of
depression, the Perceived Stress Questionnaire, Rosenberg Self-Esteem Scale,
Multidimensional Scale of Perceived Social Support, and open-ended questions were
administered to students at the end of a class. Simultaneous multiple regression
was used to examine predictors of stress. Content analysis was used to analyze
qualitative data. RESULTS: Predictors of stress for both the accelerated and
generic groups included history of depression, year in the program, emotional
support, and self-esteem. Fear of failure and clinical incompetence, problematic
relationships, and time management issues were identified as major stressors.
Coping strategies used by both groups included positive thinking and social
support. CONCLUSIONS: Senior students with a history of depression, low self
esteem, and little social support were more likely to experience high levels of
stress. This gives educators the potential to identify at risk students and
establish stress reduction programs. Encouraging students to use individualized
coping strategies will be beneficial.
PMID- 25127929
TI - Refractive lens exchange.
AB - Advances in small incision surgery have enabled cataract surgery to evolve from
being concerned primarily with the safe removal of the opaque crystalline lens to
a procedure refined to yield the best possible postoperative refractive result.
As the outcomes of cataract surgery have improved, the use of lens surgery as a
refractive modality in patients without cataracts (clear lens extraction) has
increased in popularity. The removal of the crystalline lens for refractive
purposes, or so-called refractive lens exchange (RLE), offers distinct advantages
over corneal refractive surgery in selected cases. Nevertheless, in some middle
aged patients with high refractive errors, corneal refractive surgery can be a
safe and effective treatment. In addition, the use of multifocal lenses offers an
alternative for the correction of presbyopia. A further advantage of RLE is that
it simultaneously eliminates the need for cataract surgery in the future. The
keys for success in RLE are effectiveness and consistency in the refractive
outcome, providing at the same time surgical and postoperative safety. To achieve
these goals, adequate indications following strict risk/benefit criteria and
refractive precision based on accurate preoperative protocols for IOL calculation
and selection are mandatory, together with an appropriate choice of surgical
procedure based on the surgeon's skills, minimizing complications.
PMID- 25127927
TI - Moderating effect of working memory capacity on acute alcohol effects on BOLD
response during inhibition and error monitoring in male heavy drinkers.
AB - RATIONALE: While alcohol intoxication is known to increase disinhibited behavior,
the degree to which disinhibition occurs appears to depend on a number of factors
including executive functioning ability. However, the neural mechanisms by which
individual differences in executive functioning lead to variable degrees of
disinhibition remain unclear. OBJECTIVES: The aim of the current study was to
examine the neural mechanisms by which individual differences in working memory
(WM) capacity moderate alcohol-induced disinhibition. METHODS: Seventeen heavy
drinking males participated in a within-subjects design in which two sessions
were completed: an alcohol session (.82 g/kg) and a control session. Participants
completed a go/no-go task while undergoing functional magnetic resonance imaging
(fMRI) after ingestion of the control or alcohol beverage. WM capacity was
measured using an operation span task. RESULTS: Significant interactions of
session and WM capacity emerged in contrasts examining successful response
inhibition within superior temporal gyrus and unsuccessful inhibition in regions
within the default mode network. In all cases, individuals with low WM capacity
demonstrated a relative decrease in blood oxygen level-dependent (BOLD) response
during the alcohol compared to control session, whereas the high-WM-capacity
group demonstrated relative increases in BOLD response in the alcohol compared to
control session. CONCLUSIONS: Low WM capacity appears to be associated with
decreased neural response to signals indicating a need for behavioral control, an
effect that may lead to increased difficulty with inhibiting responses and
increased negative consequences from alcohol intoxication.
PMID- 25127930
TI - Successful nonsurgical endodontic outcome of a severely affected permanent
maxillary canine with dens invaginatus Oehlers type 3.
AB - INTRODUCTION: The morphogenic complexities of dens invaginatus (DI) Oehlers type
3 in maxillary canines offer significant endodontic challenges. METHODS: A case
report is provided of a 14-year-old female patient who presented with an
anomalous-looking permanent maxillary canine associated with a sinus tract. Pulp
testing revealed a normal response on the distal aspect of the tooth, whereas the
mesial segment tested nonresponsive. A radiolucent lesion was seen on the
mesiolateral radicular area adjacent to the severely distended pulp chamber. A
gutta-percha point inserted into the sinus tract traced to this same region. The
diagnosis was normal pulp coincident with DI Oehlers type 3 with pulp necrosis
and chronic apical abscess. RESULTS: Despite a concerted effort to limit the root
canal therapy to only the necrotic canal, its proximity to the normal canal
obviated this possibility, entailing endodontic treatment of the entire root
canal system. The necrotic pulp space was subjected to sustained irrigation with
5.25% sodium hypochlorite and then completed with 17% ethylenediaminetetraacetic
acid. A bolus of gutta-percha was used to create an apical barrier, and then the
remainder of the enlarged pulp space was obturated with injectable
thermoplasticized gutta-percha. At a 4.5-year recall, there was no clinical and
radiographic evidence of infection. CONCLUSIONS: Endodontic success was
accomplished with meticulous efforts of disinfection. Thermoplasticized gutta
percha can offer utility for obturation of anatomically complicated pulp spaces.
The use of the dental operating microscope is an invaluable aid for discernment
of the intricacies of teeth affected with DI type 3 variant and can enhance
clinical outcomes.
PMID- 25127931
TI - Cell attachment properties of Portland cement-based endodontic materials:
biological and methodological considerations.
AB - INTRODUCTION: The attachment and spreading of mammalian cells on endodontic
biomaterials are an area of active research. The purpose of this review is to
discuss the cell attachment properties of Portland cement (PC)-based materials by
using scanning electron microscope (SEM). In addition, methodological aspects and
technical challenges are discussed. METHODS: A PubMed electronic search was
conducted by using appropriate key words to identify the available investigations
on the cell attachment properties of PC-based endodontic materials. After
retrieving the full text of related articles, the cross citations were also
identified. RESULTS: A total of 23 articles published between January 1993 and
October 2013 were identified. This review summarizes the cell attachment
properties of commercial and experimental PC-based materials on different cell
cultures by using SEM. Methodological procedures, technical challenges, and
relevance of SEM in determining the biological profile of PC-based materials are
discussed. CONCLUSIONS: SEM observations demonstrate that commercial MTA
formulations show favorable cell attachment properties, which is consistent with
their successful clinical outcomes. The favorable cell attachment properties of
PC and its modified formulations support its potential use as a substitute for
mineral trioxide aggregate. However, researchers should carefully select cell
types for their SEM investigations that would be in contact with the proposed PC
based combinations in the clinical situation. Despite being a technical
challenge, SEM provides useful information on the cell attachment properties of
PC-based materials; however, other assays for cell proliferation and viability
are essential to come up with an accurate in vitro biological profile of any
given PC-based formulation.
PMID- 25127932
TI - Effect of ProTaper Universal, Endoflare, Revo-S, HyFlex coronal flaring
instruments, and Gates Glidden drills on crack formation.
AB - INTRODUCTION: The aim of the present study was to evaluate crack formation after
flaring root canals with Gates Glidden drills and ProTaper Universal (SX;
Dentsply Maillefer, Ballaigues, Switzerland), Endoflare (MicroMega, Besancon,
France), Revo-S (MicroMega), and HyFlex (Coltene-Whaledent, Allstetten,
Switzerland) flaring instruments. METHODS: One-hundred eight mandibular molars
were selected. Eighteen teeth were left unprepared to serve as negative controls;
the experimental groups consisted of the mesiobuccal and mesiolingual root canals
of the remaining 90 teeth, which were instrumented with the following coronal
flaring instruments: Gates Glidden drills and ProTaper Universal SX, Endoflare,
Revo-S SC1, and HyFlex 25.08 instruments. All roots were then sectioned
perpendicular to the long axis at 1, 2, 3, 4, 6, and 8 mm from the cementoenamel
junction. The sections were inspected under a stereomicroscope, and any crack
formations were recorded. The data were analyzed using the chi-square test (P =
.05). RESULTS: The Gates Glidden drills resulted in a higher rate of crack
formation than that noted in the control group (P < .05). Flaring of the root
canals using the ProTaper Universal, Endoflare, Revo-S, and HyFlex instruments
resulted in crack formation similar to that of the control group (P > .05).
CONCLUSIONS: The use of the Gates Glidden drills resulted in the formation of the
most cracks. However, the results for the ProTaper Universal, Endoflare, Revo-S,
and HyFlex flaring instruments were similar to those of the control group in
terms of crack formation.
PMID- 25127933
TI - Enterococcus faecalis activates caspase-1 leading to increased interleukin-1 beta
secretion in macrophages.
AB - INTRODUCTION: Recent studies of inflammasome activation have focused on the
pathogenesis of diverse inflammatory and autoimmune diseases. Inflammasome
activation results in caspase-1 activation, which is required for processing of
prointerleukin (IL)-1 beta to its secreted form as well as a proinflammatory cell
death (ie, pyroptosis). The purpose of this study was to analyze whether
Enterococcus faecalis associated with endodontic infection induces inflammasome
activation. METHODS: THP-1 macrophages were treated with E. faecalis in the
presence or absence of caspase-1 inhibitors. Caspase-1 activation, pro-IL-1 beta
expression, and IL-1 beta secretion were detected by immunoblotting, real-time
reverse-transcription polymerase chain reaction, and enzyme-linked immunosorbent
assay, respectively. Cell death was measured by lactate dehydrogenase release and
propidium iodide staining. Adenosine triphosphate (ATP) release was measured by
an ATP bioluminescence assay kit. RESULTS: E. faecalis induced caspase-1
activation and pro-IL-1 beta expression, which resulted in IL-1 beta secretion in
macrophages. E. faecalis significantly induced ATP release, which is a mechanism
of Nod-like receptor family protein 3 (NLRP3) inflammasome activation, whereas
oxATP treatment inhibited E. faecalis-induced caspase-1 activation. E. faecalis
significantly increased lactate dehydrogenase release and propidium iodide
uptake, which are characteristics of pyroptosis. CONCLUSIONS: Our results show
that E. faecalis may contribute to the progression of pulpal inflammation by
stimulating excessive secretion of IL-1 beta and cell death.
PMID- 25127934
TI - Evaluation of cone-beam computed tomography in the diagnosis of vertical root
fractures: the influence of imaging modes and root canal materials.
AB - INTRODUCTION: The purpose of this study was to evaluate the influence of cone
beam computed tomography (CBCT) imaging modes in the diagnosis of vertical root
fractures with different intracanal materials. METHODS: The sample consisted of
30 single-rooted teeth divided into 3 groups (n = 10), control and complete and
incomplete root fracture. In each tooth, different materials were used (gutta
percha, metal post, and fiber post) as well as no filling material. Each
tooth/root was scanned in a 3D Accuitomo 170 CBCT device by using 4 different
imaging modes (high-resolution, high-fidelity, high-speed, and standard). In
addition, the dose-area product was calculated for each CBCT imaging mode. The
images were randomly evaluated by 5 dentomaxillofacial radiologists. RESULTS:
Complete root fractures were visualized more easily than incomplete fractures.
The presence of metal post and gutta-percha negatively influenced the diagnosis
of root fracture. Regarding the CBCT imaging modes, there was no influence for
complete root fracture diagnosis. In cases of incomplete root fractures, high
fidelity, high-resolution, and standard had a higher diagnostic accuracy,
especially in the fiber post and no filling groups. CONCLUSIONS: The CBCT imaging
modes had little influence in the diagnosis of complete and incomplete root
fractures, whereas the presence of intracanal material had greater impact on the
diagnostic ability, demonstrating that CBCT is not beneficial for the diagnosis
of root fractures when metal posts are present.
PMID- 25127935
TI - The effect of larger apical preparations in the danger zone of lower molars
prepared using the Mtwo and Reciproc systems.
AB - INTRODUCTION: The aim of this study was to evaluate the effects of large apical
preparations in the danger zones of the mesial root canals of mandibular molars
instrumented with the Mtwo and Reciproc systems (VDW, Munich, Germany) until
reaching apical diameters of 0.25 and 0.40 mm. METHODS: Twelve mandibular molars,
the mesial roots of which presented distinct foramens and similar anatomies, were
selected using micro-computed tomographic scanning. Mtwo and Reciproc instruments
were used to shape the mesiobuccal or mesiolingual canals. The mesial canals were
scanned before and after the use of 0.25- and 0.40-mm Mtwo and Reciproc
instruments. The analyzed parameters included the root canal volume and remaining
dentin thickness at 5 different levels. The obtained data were subjected to
paired analysis of variance and Tukey or Friedman and Dunn tests for intragroup
analysis and the Mann-Whitney U test for comparison between the mesial and distal
walls. RESULTS: There were no significant differences between the mesial and
distal dentin thickness for the points analyzed with both instrumentation
techniques (P > .05). The volumetric analysis revealed a significant difference
(P < .05) among the initial volume and after the use of the 0.25- and 0.40-mm
instruments for both systems. The use of the 0.40-mm instrument increased the
root canal volume in comparison to the 0.25-mm instrument (P < .05). CONCLUSIONS:
Both systems performed similarly for the preparation of curved root canals with
separate apical foramens. The increase of the root canal preparation with the
0.40-mm instrument significantly increased the root canal volume at the apical
third without significantly reducing the dentin thickness in the danger zone for
both instrument systems.
PMID- 25127937
TI - Associations between food consumption habits with meal intake behaviour in
Spanish adults.
AB - The aim of the present study is to explore the contribution of different types of
meal intake behaviour on a healthy diet and seeks to find associations with food
consumption habits. A cross-sectional survey with data from 1332 Spanish adults
aged between 20 and 79 years was conducted. The survey was carried out during the
cardiovascular health event 'Semanas del Corazon 2008' in four Spanish cities.
Several food consumption habits such as the recommended intake of fruits,
vegetables, milk and dairy products, as well as the regular consumption of fatty
and salty food and ready-made meals, were used as dependent variables in logistic
regression. We evaluated different meal intake behaviour such as the type of
meals, snacking, and drinks taken with a meal. Our survey revealed that snacking
is positively associated with the regular consumption of salty and fatty food,
and having sugary drinks with meals was positively associated with the regular
consumption of ready-made meals. Having a forenoon meal is positively associated
with the consumption of two or more portions of milk and dairy products and
vegetables, and taking an afternoon meal with the recommended intake of milk and
dairy products and fruits. Drinking water during a meal increases the probability
of consuming two or more portions of fruits and vegetables. Our results enhance
the understanding of the contribution that meal intake behaviour makes to a
healthy diet based on food consumption habits. This work provides an insight into
eating behaviour and would make a useful contribution to interventions aimed at
promoting healthier eating habits.
PMID- 25127936
TI - Hydrogen sulfide mitigates hyperglycemic remodeling via liver kinase B1-adenosine
monophosphate-activated protein kinase signaling.
AB - Hyperglycemia (HG) reduces AMPK activation leading to impaired autophagy and
matrix accumulation. Hydrogen sulfide (H2S) treatment improves HG-induced
renovascular remodeling however, its mechanism remains unclear. Activation of
LKB1 by the formation of heterotrimeric complex with STRAD and MO25 is known to
activate AMPK. We hypothesized that in HG; H2S induces autophagy and modulates
matrix synthesis through AMPK-dependent LKB1/STRAD/MO25 complex formation. To
address this hypothesis, mouse glomerular endothelial cells were treated with
normal and high glucose in the absence or presence of sodium hydrogen sulfide
(NaHS), an H2S donor. HG decreased the expression of H2S regulating enzymes CBS
and CSE, and autophagy markers Atg5, Atg7, Atg3 and LC3B/A ratio. HG increased
galectin-3 and periostin, markers of matrix accumulation. Treatment with NaHS to
HG cells increased LKB1/STRAD/MO25 formation and AMPK phosphorylation. Silencing
the encoded genes confirmed complex formation under normoglycemia. H2S-mediated
AMPK activation in HG was associated with upregulation of autophagy and
diminished matrix accumulation. We conclude that H2S mitigates adverse remodeling
in HG by induction of autophagy and regulation of matrix metabolism through
LKB1/STRAD/MO25 dependent pathway.
PMID- 25127938
TI - Esophageal diseases.
PMID- 25127939
TI - Endoscopy innovations.
PMID- 25127940
TI - Endoscopic ultrasound.
PMID- 25127941
TI - Endoscopic retrograde cholangiopancreatography.
PMID- 25127942
TI - Gastrointestinal bleeding.
PMID- 25127943
TI - Capsule endoscopy and deep enteroscopy.
PMID- 25127944
TI - Colonoscopy.
PMID- 25127945
TI - Colon adenoma surveillance: it takes a program.
PMID- 25127946
TI - Colonoscopy preparations: clearing things up.
PMID- 25127947
TI - Optical biopsy approaches in Barrett's esophagus with next-generation optical
coherence tomography.
PMID- 25127948
TI - EUS-guided pancreatic duct rendezvous in a child with traumatic pancreatic duct
disruption.
PMID- 25127949
TI - Magnetic compression anastomosis through EUS-guided choledochoduodenostomy to
repair a disconnected bile duct in orthotopic liver transplantation.
PMID- 25127950
TI - Acute duodenal diverticulitis treated with endoscopic therapy.
PMID- 25127951
TI - Therapy of rectal carcinoids of 11 to 19 mm: a matter of debate.
PMID- 25127952
TI - EUS-guided gold fiducial placement and migration rate.
PMID- 25127953
TI - Response:.
PMID- 25127954
TI - Repair of esophageal perforations using a novel endoscopic suturing system.
PMID- 25127955
TI - Insulated-tip dissecting knife to treat Zenker's diverticulum: is insulation the
key?
PMID- 25127956
TI - Suction tenting for polypectomy.
PMID- 25127957
TI - Set higher adenomas per colonoscopy benchmark.
PMID- 25127958
TI - Response:.
PMID- 25127959
TI - Premature atherosclerosis, extremely low HDL-cholesterol and concurrent defects
in APOA1 and ABCA1 genes: a family case report.
PMID- 25127960
TI - Adherence to guidelines and mortality in atrial fibrillation.
AB - OBJECTIVE: Determining the adherence to ACC/AHA/ESC 2006 guidelines and its
influence on the survival of patients with atrial fibrillation. METHODS:
Prospective observational study of patients discharged during 2007 from an
Internal Medicine department with a main or secondary diagnose of atrial
fibrillation. The stroke risk was estimated with the CHADS2 score. The follow-up
was carried out in outpatient medical office or via telephone. RESULTS: We
included 259 patients (mean age 80.9 years); 73% of them had a high risk of
stroke. Oral anticoagulants were administered to 134 (51.7%), and antiplatelet
drugs to 71 (27%) patients. A rate control strategy was chosen for 155 (59.8%)
patients and a rhythm control one for 28 (10.8%). In 100 (38.6%) patients,
treatment was adherent to the guidelines. Adherence to the guidelines was
associated with age (0.95 95%CI 0.92-0.99; p=0.03), contraindication to the use
of oral anticoagulants (0.38 95%CI 0.18-0.81; p=0.01) and mitral valve heart
disease/valvular prosthesis (2.10 95%CI 1.04-4.25; p=0.04). The median follow-up
was 727 days, and 191 patients died. Patients treated according to the guidelines
had a higher rate of survival during the first three years (0.47 vs. 0.36;
p=0.049). The use of oral anticoagulants was associated with a higher probability
of survival over a 5 year period (0.34 vs 0.21; p=0.001) and the rate control
strategy during the first year (0.69 vs 0.57; p=0.04). CONCLUSIONS: In the real
world, the treatment of atrial fibrillation according to the guidelines is
associated with improved survival for up to three years during follow-up.
PMID- 25127962
TI - Response to the comment letter about adjustment.
PMID- 25127961
TI - The association of asthma and atrial fibrillation--a nationwide population-based
nested case-control study.
AB - BACKGROUND: Asthma and atrial fibrillation (AF) have been reported to be related
to an increased risk of cardiovascular events. However, the relationship between
asthma and AF has not been fully elucidated. The purpose of this study was to
examine the association between asthma and AF risk. METHODS: We conducted a
population-based nested case-control study including a total of 7439 newly
diagnosed adult patients with AF and 10,075 age-, gender-, comorbidity-, and
cohort entry date-matched subjects without AF from the Taiwan National Health
Insurance database. Exposure to asthma as well as medications including
bronchodilators and corticosteroid before the index date was evaluated to
investigate the association between AF and asthma as well as concurrent
medications. RESULTS: AF patients were 1.2 times (adjusted OR 1.2, 95% CI 1.109
1.298) more likely to be associated with a future occurrence of asthma
independent of comorbidities and treatment with corticosteroids and
bronchodilator. In addition, the risks of new-onset AF were significantly higher
among current users of inhaled corticosteroid, oral corticosteroids, and
bronchodilators. Newly users (within 6 months) have the highest risk (inhaled
corticosteroid: OR, 2.13; 95% CI, 1.226-3.701, P=0.007; oral corticosteroid: OR,
1.932; 95% CI, 1.66-2.25, P<0.001; non-steroid bronchodilator: OR, 2.849; 95% CI,
2.48-3.273, P<0.001). A graded association with AF risk was also observed among
subjects treated with corticosteroid (inhaled and systemic administration) and
bronchodilators. New users (within 6 months) of these medications had the highest
risk of AF (ICS: OR, 2.13; 95% CI, 1.226-3.701, P=0.007; oral corticosteroid: OR,
1.932; 95% CI, 1.66-2.25, P<0.001; non-steroid bronchodilator: OR, 2.849; 95% CI,
2.48-3.273, P<0.001). A graded association with AF risk was also observed among
subjects treated with ICS or bronchodilator. CONCLUSIONS: Asthma was associated
with an increased risk of developing future AF.
PMID- 25127963
TI - Association between chronic obstructive pulmonary disease and tako tsubo
cardiomyopathy--a case report.
PMID- 25127964
TI - Left ventricular rhabdomyoma in an adult patient: a rare disease successfully
treated.
PMID- 25127965
TI - Left ventricular outflow tract obstruction as a primary phenotypic expression of
hypertrophic cardiomyopathy in mutation carriers without hypertrophy.
PMID- 25127966
TI - Excess mortality in women compared to men after PCI in STEMI: an analysis of
11,931 patients during 2000-2009.
AB - BACKGROUND: Ambiguity exists whether gender affects outcome in patients
undergoing percutaneous coronary intervention (PCI). METHODS: To evaluate the
relationship between gender and outcome in a large cohort of PCI patients, 11,931
consecutive patients who underwent PCI for various indications during 2000-2009
were studied using survival analyses and Cox regression models. RESULTS: Most
patients (n=8588; 72%) were men. Women were older and more often had a history of
hypertension and diabetes mellitus. Men smoked more frequently, had a more
extensive cardiovascular history (previous MI, PCI and CABG), a higher prevalence
of renal impairment and multi-vessel disease. In STEMI patients, women had higher
31-day mortality rates than men (11.6% vs. 6.5%, respectively, p<0.001). This
difference remained after adjustment for confounders (aHR at 30-days 1.54 and 95%
CI 1.22-1.96). Likewise, higher mortality was observed at 1-year (15.1% vs. 9.3%)
and 4-year follow-up (21.6% vs. 15.0%, aHR 1.30 and 95% CI 1.10-1.53). There were
no differences in mortality between women and men in NSTE-ACS (aHR at 4-years
1.05 and 95% CI 0.85-1.28) or stable angina (HR at 4-years 0.85 and 95% CI 0.68
1.08). CONCLUSION: Women undergoing PCI for STEMI had higher mortality than men.
The excess mortality in women appeared in the first month after PCI and could
only partially be explained by a difference in baseline characteristics. No
gender differences in outcome in patients undergoing PCI for NSTE-ACS and stable
angina were observed.
PMID- 25127967
TI - Sodium tanshinone IIA sulfonate and sodium danshensu open the placental barrier
through down-regulation of placental P-glycoprotein in mice: implications in the
transplacental digoxin treatment for fetal heart failure.
PMID- 25127968
TI - Relationship of subcutaneous fat distributional pattern to blood pressure levels
among children and adolescents in Shandong, China.
PMID- 25127969
TI - Impact of single versus double vessel carotid disease on long-term survival in
patients treated with carotid stenting.
PMID- 25127970
TI - Warfarin-related nephropathy: prevalence, risk factors and prognosis.
PMID- 25127971
TI - Urban-rural and regional disparities in the prevalence of elevated blood pressure
among children and adolescents in Shandong, China.
PMID- 25127972
TI - Electrocardiographic findings of secondary arrhythmogenic right ventricular
cardiomyopathy in different right ventricular abnormalities: re.: Secondary
arrhythmogenic right ventricular cardiomyopathy after decades of operative repair
of tetralogy of Fallot.
PMID- 25127973
TI - High-sensitivity cardiac troponin for risk prediction in patients with and
without coronary heart disease.
AB - BACKGROUND: In stable patients with unknown coronary anatomy, higher levels of
cardiac troponin are associated with an increased risk of cardiovascular events.
It was supposed that this association might be explained by the ability of
cardiac troponin to detect minor myocardial necrosis which might be caused by
subclinical coronary atherosclerosis. Thus, this analysis tested if the
predictive value of high-sensitivity troponin T (hsTnT) in stable patients is
dependent of the presence or absence of angiographically documented coronary
heart disease. METHODS: Stable patients undergoing elective coronary angiography
were enrolled (n=2046). HsTnT was determined before diagnostic procedures. The
patients were followed for up to seven years. Primary endpoint was all-cause
mortality or non-fatal myocardial infarction. All endpoints were adjudicated by
independent physicians. Results were adjusted to a clinical model including
independent clinical predictors of the primary endpoint. RESULTS: Out of the 2046
patients enrolled, 1236 (60%) had a diagnosis of obstructive coronary heart
disease. HsTnT predicted independently the primary endpoint (adjusted HR 1.33,
95%-CI 1.21-1.46, P<0.001). The use of hsTnT in addition to the clinical model
significantly improved discrimination (c-statistic: 0.751 to 0.773, P<0.001) as
well as reclassification of the primary endpoint (NRI=0.362, P<0.001). This
significant improvement persisted across various subsets and was independent of
the presence of clinically detectable coronary heart disease and other variables.
CONCLUSION: The use of hsTnT in addition to clinical variables significantly
improves discrimination and reclassification of patients with respect to all
cause mortality or non-fatal myocardial infarction irrespective of the presence
of clinically detectable coronary heart disease. CLINICAL TRIAL REGISTRATION:
ClinicalTrials.gov (Identifier: NCT00457236).
PMID- 25127974
TI - Intramyocellular lipid is increased in the skeletal muscle of patients with
dilated cardiomyopathy with lowered exercise capacity.
PMID- 25127975
TI - Amplatzer vascular plug for patent ductus arteriosus migrated to pulmonary artery
six months after closure in a 59 year old female.
PMID- 25127976
TI - Prolonged effectiveness of coronary artery bypass surgery versus drug-eluting
stents in diabetics with multi-vessel disease: an updated systematic review and
meta-analysis.
AB - BACKGROUND: Currently, the appropriateness of percutaneous coronary intervention
(PCI) using drug-eluting stents (DES) versus coronary artery bypass grafting
(CABG) for patients with diabetes (DM) and multi-vessel disease (MVD) is
uncertain due to limited evidence from few randomised controlled trials (RCTs).
We aimed to compare the clinical effectiveness of CABG versus PCI-DES in DM-MVD
patients using an evidence-based approach. METHODS: A systematic review and meta
analyses were conducted to compare the risk of all-cause mortality, myocardial
infarction (MI), repeat revascularisation, cerebrovascular events (CVE), and
major adverse cardiac or cerebrovascular events (MACCE). RESULTS: A total of
1,837 and 3,052 DM-MVD patients were pooled from four RCTs (FREEDOM, SYNTAX, VA
CARDS, and CARDia) and five non-randomised studies. At mean follow-up of 3 years,
CABG compared with PCI-DES was associated with a lower risk of all-cause
mortality and MI in RCTs. By contrast, no significant differences were observed
in the mean 3.5-year risk of all-cause mortality and MI in non-randomised trials.
However, the risk of repeat revascularisations following PCI-DES compared with
CABG was 2.3 (95% CI=1.8-2.8) and 3.0 (2.3-4.2)-folds higher in RCTs and non
randomised trials, respectively. Accordingly, the risk of MACCE at 3 years
following CABG compared with PCI-DES was lower in both RCTs and non-randomised
trials [0.65 (: 0.55-0.77); and 0.77 (0.60-0.98), respectively]. CONCLUSIONS:
Based on our pooled results, we recommend CABG compared with PCI-DES for patients
with DM-MVD. Although non-randomised trials suggest no additional survival-, MI-,
and CVE- benefit from CABG over PCI-DES, these results should be interpreted with
care.
PMID- 25127977
TI - Effect of repeat twice daily sessions of remote ischemic conditioning over the
course of one week on blood pressure of a normotensive/prehypertensive subject.
PMID- 25127978
TI - Acute coronary syndrome and coronary intervention in a patient with type 2M von
Willebrand disease.
PMID- 25127979
TI - Aborted sudden cardiac death due to intractable ventricular fibrillation caused
by coronary spasm refractory to implantable cardioverter defibrillator therapy.
PMID- 25127980
TI - Chronic constrictive pericarditis in general adult population.
PMID- 25127981
TI - Retracted: Significant variations in afferent conduction and axonal morphology of
aortic depressive nerve imply broader spectrum of baroreflex function of
myelinated Ah-type baroreceptor neurons in female rats.
PMID- 25127982
TI - Active coping toward predatory stress is associated with lower corticosterone and
progesterone plasma levels and decreased methylation in the medial amygdala
vasopressin system.
AB - An active coping style displayed under stress - which involves proactive
investigatory responses toward environmental threats - has been associated with
reduced vulnerability to psychiatric illness. However, the neurobiological
determinants of coping styles are not well understood. When rats are exposed to a
naturalistic stressor (cat fur) in a group, some individuals in the group show
robust active investigation of the stimulus while others show a passive response
involving retreat, immobility and close aggregation with conspecifics. Here we
explored endocrine and epigenetic correlates of these contrasting coping styles.
Male Wistar rats (n=48) were exposed to cat fur in groups of 4 and the passive
and active responders were identified and assessed for endocrine and epigenetic
differences. Three days after the final cat fur exposure, active responders had
substantially lower plasma levels of corticosterone and progesterone than passive
responders. Plasma and testicular testosterone levels did not differ between
active and passive responders. Active responders had markedly less methylation of
the AVP CGCG promoter region located at base 4970 in the posterodorsal region of
the medial amygdala but did not differ in the methylation status of the CCGG
sequence located at base 2243. This is in agreement with prior research
suggesting that AVP and progesterone act in opposition within the medial amygdala
to modulate stress-related behaviors. The present study reports striking
endocrine and epigenetic differences between active and passive responders,
providing insight into potential systems involved in the manifestation of
differing coping styles.
PMID- 25127983
TI - Endurance training minimizes age-related changes of left ventricular twist
untwist mechanics.
AB - BACKGROUND: The aim of this study was to test the effect of endurance training on
the age-related changes of left ventricular (LV) twist-untwist mechanics. Aging
has been shown to induce a decline of diastolic function and more recently an
impairment of twist-untwist mechanics, which constitutes an important factor for
early diastolic suction and filling. On the other hand, endurance training has
been shown to improve cardiac function. METHODS: Speckle-tracking
echocardiography was performed in 106 endurance-trained male athletes and 75
controls (age range 18-70 years), divided into three groups according to age.
RESULTS: From the younger to older age groups, progressive increases in LV apical
rotation and twist angle and a decrease in LV untwisting rate during isovolumic
relaxation time were observed. Athletes had lower systolic twist angles (P < .01)
but higher untwist/twist ratios and LV untwisting rate during isovolumic
relaxation time compared with controls, with the largest difference between
senior groups (51 +/- 24% vs 42 +/- 22% in the young and 42 +/- 29% vs 24 +/- 25%
in seniors, P < .001, respectively). The normal timing of untwisting rate
occurring before radial displacement was preserved in athletes with increasing
age, whereas it was blunted in controls. CONCLUSIONS: Endurance training does not
prevent but minimizes changes in LV twist-untwist mechanics from young subjects
to seniors. Athletes showed smaller increases of twist angle with age and smaller
declines of LV untwisting rate during isovolumic relaxation time and
untwist/twist ratio compared with controls. This training-improved preservation
of LV twist-untwist mechanics is likely to play a key role for systolic-diastolic
coupling and diastolic filling, particularly during exercise.
PMID- 25127984
TI - Effect of gadolinium injection on diffusion-weighted imaging with background body
signal suppression (DWIBS) imaging of breast lesions.
AB - OBJECTIVES: Diffusion-weighted imaging with background body signal suppression
(DWIBS) provides both qualitative and quantitative imaging of breast lesions and
are usually performed before contrast material injection (CMI). This study aims
to assess whether the administration of gadolinium significantly affects DWIBS
imaging. METHODS: 200 patients were prospectively evaluated by MRI with STIR, TSE
T2, pre-CMI DWIBS, contrast enhanced THRIVE-T1 and post-CMI DWIBS sequences. Pre
and post-CMI DWIBS were analyzed searching for the presence of breast lesions and
calculating the ADC value. ADC values of <=1.44*10(-3) mm(2)/s were considered
suspicious for malignancy. This analysis was then compared with the histological
findings. Sensitivity, specificity, diagnostic accuracy (DA), positive predictive
value (PPV) and negative (NPV) were calculated for both sequences and represented
by ROC analysis. Pre and post-CMI ADC values were compared by using the paired t
test. RESULTS: In 150/200 (59%) patients, pre and post-CMI DWIBS indicated the
presence of breast lesions, 53 (35%) with ADC values of >1.44*10(-3) mm(2)/s and
97 (65%) with ADC<=1.44*10(-3) mm(2)/s. Pre-CMI and post-DWIBS sequences obtained
the same sensitivity, specificity, DA, PPV and NPV values of 97%, 83%, 89%, 79%
and 98%. The mean ADC value of benign lesions was 1.831+/-0.18*10(-3) mm(2)/s
before and 1.828+/-0.18*10(-3) mm(2)/s after CMI. The mean ADC value of the
malignant lesions was 1.146+/-0.16*10(-3) mm(2)/s before and 1.144+/-0.16*10(-3)
mm(2)/s after CMI. No significant difference was found between pre and post CMI
ADC values (p>0.05). CONCLUSION: DWIBS imaging is not influenced by CMI. Breast
MR protocol could be modified by placing DWIBS after dynamic contrast enhanced
sequences in order to maximize patient cooperation.
PMID- 25127985
TI - [Pulmonary hypertension: definition, diagnostic and new classification].
AB - Pulmonary hypertension (PH): mean pulmonary arterial pressure (mPAP) >= 25 mm Hg
on right heart catheterization at rest. Pulmonary arterial hypertension (PAH):
mPAP >= 25 mm Hg, pulmonary capillary wedge pressure (PCWP) <= 15 mm Hg and
pulmonary vascular resistances (PVR) >3 Wood units. Patients with compatible
symptoms (exertional dyspnea, syncopes, signes of right heart failure) can show
signs of PH on cardiac echography and therefore need to be investigated in search
of the cause of PH. After ruling out the frequent causes of PH (left heart and
chronic respiratory diseases), the V/Q lung scan is used to screen for patients
with post-embolic PH, that need to be further investigated hemodynamically and
radiologically in order to decide operability. For the rest of the patients, only
right heart catheterization can identify patients with precapillary PH and these
patients must be further evaluated (clinically, by blood samples and by imaging
techniques) in order to be classified in one the PH groups of the classification.
For the future the discovery of novel risk factors and understanding the
mechanism involved with the already known ones represent two major points of
research.
PMID- 25127986
TI - Accuracy of colposcopy in HIV seropositive and seronegative women with abnormal
Pap tests.
AB - OBJECTIVE: The aim of this study is to compare colposcopic findings and the
accuracy of colposcopic impression in HIV seropositive and seronegative women
with abnormal Pap tests. METHODS: HIV seropositive and seronegative women in a
national cohort study had Pap tests collected every six months, with colposcopy
for any abnormal result. Prospectively collected colposcopy and histology
findings were analyzed retrospectively using Pearson Chi-square, t-test and
Wilcoxon two-sample tests, logistic regression models, and Kappa coefficients.
RESULTS: After adjusting for age and Pap result, 1618 eligible HIV seropositive
women were more likely than 406 seronegative women to have inadequate colposcopic
examinations, abnormal colposcopic findings, and large cervical lesions. However,
among those with abnormal colposcopy, colposcopic characteristics and lesion size
and number did not differ by HIV serostatus. Agreement between colposcopists'
impressions and highest grade biopsy diagnoses was fair (kappa coefficient 0.35,
95% C.I. 0.31, 0.38). Agreement did not differ by HIV serostatus and did not
improve with multiple biopsies (weighted kappa coefficient 0.35, 95% C.I. 0.32,
0.39) or after including all histology results over two years following
colposcopy. CONCLUSION: Although HIV seropositive women with abnormal cytology
are more likely to have colposcopic abnormality, the performance of colposcopy
appears to be similar to that in HIV seronegative women. Biopsy is required to
confirm colposcopic impression.
PMID- 25127987
TI - Polymorphisms in immune mediators associate with risk of cervical cancer.
AB - OBJECTIVE: The immune system is critical for controlling the progression of HPV
cervical disease and the development of cancer. This study aimed to identify
cervical cancer susceptibility alleles in candidate immune-modulating genes.
METHODS: Our family-based study involved a cohort of 641 probands (women with
ICC/CIN III) and their biologic parents or siblings (641 trios). In the discovery
phase (stage 1), involving 288 of the trios, 80 tag single nucleotide
polymorphisms (SNPs) in 11 immune-modulating genes (IFNG, IFNGR1, IFNGR2, JAK1,
JAK2, STAT1, STAT6, IL12A, TNF, LTA and LTB) were evaluated on the GoldenGate
platform. We used the combined dataset for a total of 641 trios (stage 2) and the
Taqman platform to validate the SNPs that had proved significant in the discovery
dataset. The transmission disequilibrium test was used to detect significant
shifts in allelic transmissions in the datasets. RESULTS: Two SNPs in JAK2 and
one SNP in STAT6 showed significant allelic association with cervical cancer in
the stage 1 discovery dataset and were replicated in the larger joint analysis
stage 2 dataset (JAK2 rs10815144, P=0.0029 and rs12349785, P=0.0058; and STAT6
rs3024971, P=0.0127). An additional SNP in exon 19 of JAK2 (rs2230724) was also
examined in the combined dataset due to its strong linkage disequilibrium (LD)
with rs10815144. It was also significant (P=0.0335). CONCLUSIONS: Our results
suggest an association of SNPs in JAK2 and STAT6 with cervical cancer. This
association should be investigated in additional cervical cancer populations.
PMID- 25127988
TI - Abnormal CA-125 levels in menopausal women without ovarian cancer.
AB - OBJECTIVE: To determine if an abnormal CA-125 level in a menopausal female
without ovarian cancer is associated with an increase in mortality. METHODS: The
Prostate, Lung, Colorectal, and Ovarian Cancer Screening Randomized Controlled
(PLCO) Trial is a large multicenter prospective trial conducted by the National
Cancer Institute (NCI). Over 78,000 healthy women aged 55-74 were randomized to a
screening arm versus a usual medical care arm to evaluate the efficacy of
screening in reducing mortality due to ovarian cancer. Women in the screening arm
underwent annual screening for ovarian cancer with transvaginal ultrasound and CA
125 levels. There were 38,818 patients without ovarian cancer that had at least
one CA-125 level drawn; 1201 (3.09%) had at least one abnormal level. The current
study compares mortality in patients that had one or more abnormal CA-125 levels
without ovarian cancer versus those with all normal levels. RESULTS: Patients
with one or more abnormal CA-125 levels, without ovarian cancer, had a
significantly higher mortality than patients with all normal CA-125 levels in the
PLCO screening trial (p<0.0001). This increased risk extended throughout the
follow-up period. Analysis of cause of death listed on the death certificate
showed an excess mortality attributable to lung cancer, digestive disease, and
endocrine, nutritional, and metabolic disease. CONCLUSION: Menopausal females
with an elevated CA-125 and without ovarian cancer are exposed to an increased
risk of premature mortality.
PMID- 25127989
TI - Formulation and photoirradiation parameters that influenced photoresponsive drug
delivery using alkoxylphenacyl-based polycarbonates.
AB - Recently, we reported the synthesis and biocompatibility of alkoxylphenacyl-based
polycarbonates (APP); a promising new class of polymers that undergo photo
induced chain scission. In the current study, nanoparticles (NPs) were prepared
from the APP polymer (APP-NPs) and loaded with doxorubicin (DOX) (DOX-APP-NPs) in
order to identify and evaluate formulation and photoirradiation parameters that
influence photoresponsive efficacy. Stable and spherical APP-NPs were prepared
with diameters between 70-80nm depending on APP concentration (10-40mg/mL). There
was a direct relationship between APP concentration and resultant particle size.
Drug release studies indicated that exposure to the photo-trigger was capable of
altering the rate and extent of DOX released. Photoresponsive DOX release was
markedly influenced by the frequency of photoirradiation while the effect of APP
concentration was most likely propagated through NP size. DOX released by
photoactivation retained its efficacy as assessed by cytotoxicity studies in
human lung adenocarcinoma (A549) cells. Studies in BALB/c mice indicated that DOX
APP-NPs induce less cardiotoxicity than DOX alone and that DOX-APP-NPs are not
susceptible to dose dumping after photoirradiation.
PMID- 25127990
TI - Congenital myopathies with secondary neuromuscular transmission defects; a case
report and review of the literature.
AB - Congenital myopathies are a clinically and genetically heterogeneous group of
disorders characterized by early onset hypotonia, weakness and characteristic,
but not pathognomonic, structural abnormalities in muscle fibres. The clinical
features overlap with muscular dystrophies, myofibrillar myopathies, neurogenic
conditions and congenital myasthenic syndromes. We describe a case of cap
myopathy with myasthenic features due to a mutation in the TPM2 gene that
responded to anticholinesterase therapy. We also review other published cases of
congenital myopathies with neuromuscular transmission abnormalities. This report
expands the spectrum of congenital myopathies with secondary neuromuscular
transmission defects. The recognition of these cases is important since these
conditions can benefit from treatment with drugs enhancing neuromuscular
transmission.
PMID- 25127991
TI - FAK is required for tension-dependent organization of collective cell movements
in Xenopus mesendoderm.
AB - Collective cell movements are integral to biological processes such as embryonic
development and wound healing and also have a prominent role in some metastatic
cancers. In migrating Xenopus mesendoderm, traction forces are generated by cells
through integrin-based adhesions and tension transmitted across cadherin
adhesions. This is accompanied by assembly of a mechanoresponsive cadherin
adhesion complex containing keratin intermediate filaments and the catenin-family
member plakoglobin. We demonstrate that focal adhesion kinase (FAK), a major
component of integrin adhesion complexes, is required for normal morphogenesis at
gastrulation, closure of the anterior neural tube, axial elongation and
somitogenesis. Depletion of zygotically expressed FAK results in disruption of
mesendoderm tissue polarity similar to that observed when expression of keratin
or plakoglobin is inhibited. Both individual and collective migrations of
mesendoderm cells from FAK depleted embryos are slowed, cell protrusions are
disordered, and cell spreading and traction forces are decreased. Additionally,
keratin filaments fail to organize at the rear of cells in the tissue and
association of plakoglobin with cadherin is diminished. These findings suggest
that FAK is required for the tension-dependent assembly of the cadherin adhesion
complex that guides collective mesendoderm migration, perhaps by modulating the
dynamic balance of substrate traction forces and cell cohesion needed to
establish cell polarity.
PMID- 25127992
TI - The Fog signaling pathway: insights into signaling in morphogenesis.
AB - Epithelia form the building blocks of many tissue and organ types. Epithelial
cells often form a contiguous 2-dimensional sheet that is held together by strong
adhesions. The mechanical properties conferred by these adhesions allow the cells
to undergo dramatic three-dimensional morphogenetic movements while maintaining
cell-cell contacts during embryogenesis and post-embryonic development. The
Drosophila Folded gastrulation pathway triggers epithelial cell shape changes
that drive gastrulation and tissue folding and is one of the most extensively
studied examples of epithelial morphogenesis. This pathway has yielded key
insights into the signaling mechanisms and cellular machinery involved in
epithelial remodeling. In this review, we discuss principles of morphogenesis and
signaling that have been discovered through genetic and cell biological
examination of this pathway. We also consider various regulatory mechanisms and
the system's relevance to mammalian development. We propose future directions
that will continue to broaden our knowledge of morphogenesis across taxa.
PMID- 25127993
TI - Retinoic acid plays an evolutionarily conserved and biphasic role in pancreas
development.
AB - As the developing zebrafish pancreas matures, hormone-producing endocrine cells
differentiate from pancreatic Notch-responsive cells (PNCs) that reside within
the ducts. These new endocrine cells form small clusters known as secondary (2
degrees ) islets. We use the formation of 2 degrees islets in the pancreatic
tail of the larval zebrafish as a model of beta-cell neogenesis. Pharmacological
inhibition of Notch signaling leads to precocious endocrine differentiation and
the early appearance of 2 degrees islets in the tail of the pancreas. Following
a chemical screen, we discovered that blocking the retinoic acid (RA)-signaling
pathway also leads to the induction of 2 degrees islets. Conversely, the
addition of exogenous RA blocks the differentiation caused by Notch inhibition.
In this report we characterize the interaction of these two pathways. We first
verified that signaling via both RA and Notch ligands act together to regulate
pancreatic progenitor differentiation. We produced a transgenic RA reporter,
which demonstrated that PNCs directly respond to RA signaling through the
canonical transcriptional pathway. Next, using a genetic lineage tracing
approach, we demonstrated these progenitors produce endocrine cells following
inhibition of RA signaling. Lastly, inhibition of RA signaling using a cell-type
specific inducible cre/lox system revealed that RA signaling acts cell
autonomously in PNCs to regulate their differentiation. Importantly, the action
of RA inhibition on endocrine formation is evolutionarily conserved, as shown by
the differentiation of human embryonic stem cells in a model of human pancreas
development. Together, these results revealed a biphasic function for RA in
pancreatogenesis. As previously shown by others, RA initially plays an essential
role during embryogenesis as it patterns the endoderm and specifies the
pancreatic field. We reveal here that later in development RA is involved in
negatively regulating the further differentiation of pancreatic progenitors and
expands upon the developmental mechanisms by which this occurs.
PMID- 25127994
TI - Sterol carrier protein 2 regulates proximal tubule size in the Xenopus pronephric
kidney by modulating lipid rafts.
AB - The kidney is a homeostatic organ required for waste excretion and reabsorption
of water, salts and other macromolecules. To this end, a complex series of
developmental steps ensures the formation of a correctly patterned and properly
proportioned organ. While previous studies have mainly focused on the individual
signaling pathways, the formation of higher order receptor complexes in lipid
rafts is an equally important aspect. These membrane platforms are characterized
by differences in local lipid and protein compositions. Indeed, the cells in the
Xenopus pronephric kidney were positive for the lipid raft markers ganglioside
GM1 and Caveolin-1. To specifically interfere with lipid raft function in vivo,
we focused on the Sterol Carrier Protein 2 (scp2), a multifunctional protein that
is an important player in remodeling lipid raft composition. In Xenopus, scp2
mRNA was strongly expressed in differentiated epithelial structures of the
pronephric kidney. Knockdown of scp2 did not interfere with the patterning of the
kidney along its proximo-distal axis, but dramatically decreased the size of the
kidney, in particular the proximal tubules. This phenotype was accompanied by a
reduction of lipid rafts, but was independent of the peroxisomal or
transcriptional activities of scp2. Finally, disrupting lipid micro-domains by
inhibiting cholesterol synthesis using Mevinolin phenocopied the defects seen in
scp2 morphants. Together these data underscore the importance for localized
signaling platforms in the proper formation of the Xenopus kidney.
PMID- 25127996
TI - Report of the National Institutes of Health task force on research standards for
chronic low back pain.
AB - OBJECTIVES: Despite rapidly increasing intervention, functional disability due to
chronic low back pain (cLBP) has increased in recent decades. We often cannot
identify mechanisms to explain the major negative impact cLBP has on patients'
lives. Such cLBP is often termed nonspecific and may be due to multiple biologic
and behavioral etiologies. Researchers use varied inclusion criteria,
definitions, baseline assessments, and outcome measures, which impede comparisons
and consensus. The purpose of this article is to disseminate the report of the
National Institutes of Health (NIH) task force on research standards for cLBP.
METHODS: The NIH Pain Consortium charged a research task force (RTF) to draft
standards for research on cLBP. The resulting multidisciplinary panel developed a
3-stage process, each with a 2-day meeting. RESULTS: The panel recommended using
2 questions to define cLBP; classifying cLBP by its impact (defined by pain
intensity, pain interference, and physical function); use of a minimal data set
to describe research subjects (drawing heavily on the Patient Reported Outcomes
Measurement Information System methodology); reporting "responder analyses" in
addition to mean outcome scores; and suggestions for future research and
dissemination. The Pain Consortium has approved these recommendations, which
investigators should incorporate into NIH grant proposals. CONCLUSIONS: The RTF
believes that these recommendations will advance the field, help to resolve
controversies, and facilitate future research addressing the genomic, neurologic,
and other mechanistic substrates of cLBP. Greater consistency in reporting should
facilitate comparisons among studies and the development of phenotypes. We expect
the RTF recommendations will become a dynamic document and undergo continual
improvement.
PMID- 25127997
TI - Development of a neck pain risk score for predicting nonspecific neck pain with
disability in office workers: a 1-year prospective cohort study.
AB - OBJECTIVE: The purpose of this study was to develop a neck pain risk score for
office workers (NROW) to identify office workers at risk for developing
nonspecific neck pain with disability. METHODS: A 1-year prospective cohort study
of 559 healthy office workers was conducted. At baseline, risk factors were
assessed using questionnaires and standardized physical examination. The
incidence of neck pain was collected every month thereafter. Disability level was
evaluated using the neck disability index. Logistic regression was used to select
significant factors to build a risk score. The coefficients from the logistic
regression model were transformed into the components of a risk score. RESULTS:
Among 535 (96%) participants who were followed up for 1 year, 23% reported
incident neck pain with disability (>=5). After adjusting for confounders, the
onset of neck pain with disability was significantly associated with history of
neck pain, chair adjustability, and perceived muscular tension. Thus, the NROW
comprises 3 questions about history of neck pain, chair adjustability, and
perceived muscular tension. The NROW had scores ranging from 0 to 4. A cut-off
score of at least 2 had a sensitivity of 82% and specificity of 48%. The positive
and negative predictive values were 29% and 91%, respectively. The area under the
receiver operating characteristic curve was 0.75. CONCLUSION: The risk score for
nonspecific neck pain with disability in office workers was developed, and it
contained 3 items with scores ranging from 0 to 4. This study shows that the
score appears to have reasonable sensitivity, specificity, positive predictive
value, and negative predictive values for the cut-off point of at least 2.
PMID- 25127998
TI - Can functional capacity tests predict future work capacity in patients with
whiplash-associated disorders?
AB - OBJECTIVE: To determine whether functional capacity evaluation (FCE) tests
predict future work capacity (WC) of patients with whiplash-associated disorders
(WADs) grades I and II who did not regain full WC 6 to 12 weeks after injury.
DESIGN: Prospective cohort study. SETTING: Rehabilitation center. PARTICIPANTS:
Workers (N=267) listed on workers' compensation with grade I or II WADs 6 to 12
weeks after injury. INTERVENTIONS: Patients performed 8 work-related FCE tests.
MAIN OUTCOME MEASURES: WC (0-100%) measured at baseline and 1, 3, 6, and 12
months after testing. Correlation coefficients between FCE tests and WC were
calculated. A linear mixed-model analysis was used to assess the association
between FCE and future WC. RESULTS: Mean +/- SD WC increased over time from
20.8%+/-27.6% at baseline to 32.3%+/-38.4%, 51.3%+/-42.8%, 65.6%+/-42.2%, and
83.2%+/-35.0% at the 1-, 3-, 6-, and 12-month follow-ups, respectively.
Correlation coefficients between FCE tests and WC ranged from r=.06 (lifting low
at 12-mo follow-up) to r=.39 (walking speed at 3mo). Strength of the correlations
decreased over time. FCE tests did not predict WC at follow-up. The predictors of
WC were ln (time) (beta=23.74), mother language (beta=5.49), WC at baseline
(beta=1.01), and self-reported disability (beta=-.20). Two interaction terms, ln
(time) * WC (beta=-.19) and ln (time) * self-reported disability (beta=-.21),
were significant predictors of WC. CONCLUSIONS: FCE tests performed within 6 to
12 weeks after WADs injury grades I and II are associated with WC at baseline but
do not predict future WC, whereas time course, mother language, WC at baseline,
and self-reported disability do predict future WC. Additionally, the interaction
between time course WC at baseline and self-reported disability predicted future
WC.
PMID- 25127995
TI - In vivo analysis of hyaloid vasculature morphogenesis in zebrafish: A role for
the lens in maturation and maintenance of the hyaloid.
AB - Two vascular networks nourish the embryonic eye as it develops - the hyaloid
vasculature, located at the anterior of the eye between the retina and lens, and
the choroidal vasculature, located at the posterior of the eye, surrounding the
optic cup. Little is known about hyaloid development and morphogenesis, however.
To begin to identify the morphogenetic underpinnings of hyaloid formation, we
utilized in vivo time-lapse confocal imaging to characterize morphogenesis of the
zebrafish hyaloid through 5 days post fertilization (dpf). Our data segregate
hyaloid formation into three distinct morphogenetic stages: Stage I: arrival of
hyaloid cells at the lens and formation of the hyaloid loop; Stage II: formation
of a branched hyaloid network; Stage III: refinement of the hyaloid network.
Utilizing fixed and dissected tissues, distinct Stage II and Stage III aspects of
hyaloid formation were quantified over time. Combining in vivo imaging with
microangiography, we demonstrate that the hyaloid system becomes fully enclosed
by 5dpf. To begin to identify the molecular and cellular mechanisms underlying
hyaloid morphogenesis, we identified a recessive mutation in the mab21l2 gene,
and in a subset of mab21l2 mutants the lens does not form. Utilizing these "lens
less" mutants, we determined whether the lens was required for hyaloid
morphogenesis. Our data demonstrate that the lens is not required for Stage I of
hyaloid formation; however, Stages II and III of hyaloid formation are disrupted
in the absence of a lens, supporting a role for the lens in hyaloid maturation
and maintenance. Taken together, this study provides a foundation on which the
cellular, molecular and embryologic mechanisms underlying hyaloid morphogenesis
can be elucidated.
PMID- 25128000
TI - Effects of an anterior ankle-foot orthosis on walking mobility in stroke
patients: get up and go and stair walking.
AB - OBJECTIVE: To examine the effects of an anterior ankle-foot orthosis (AAFO) on
walking mobility in stroke patients. DESIGN: Cross-sectional and repeated
measures study design. SETTING: A university's neurologic rehabilitation
department. PARTICIPANTS: Ambulant stroke patients (N=21). INTERVENTIONS: Not
applicable. MAIN OUTCOME MEASURES: Walking mobility was measured by the Timed Up
and Go (TUG) test and the Timed Up and Down Stairs (TUDS) test. The paired t test
was used to determine the difference between the mobility performances measured
with and without the AAFO. RESULTS: There were significant differences between
mobility performances with and without an AAFO in the TUG test (P=.038) and the
TUDS test (P=.000). CONCLUSIONS: This study supports the effect of an AAFO on
walking mobility in stroke patients. The findings demonstrate that stroke
patients wearing an AAFO may ambulate with greater speed and safety on level
surfaces and stairs.
PMID- 25127999
TI - Carpal tunnel syndrome: hand surgeons, hand therapists, and physical medicine and
rehabilitation physicians agree on a multidisciplinary treatment guideline
results from the European HANDGUIDE Study.
AB - OBJECTIVE: To achieve consensus on a multidisciplinary treatment guideline for
carpal tunnel syndrome (CTS). DESIGN: Delphi consensus strategy. SETTING:
Systematic reviews reporting on the effectiveness of surgical and nonsurgical
interventions were conducted and used as an evidence-based starting point for a
European Delphi consensus strategy. PARTICIPANTS: In total, 35 experts (hand
surgeons selected from the Federation of European Societies for Surgery of the
Hand, hand therapists selected from the European Federation of Societies for Hand
Therapy, physical medicine and rehabilitation physicians) participated in the
Delphi consensus strategy. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
Each Delphi round consisted of a questionnaire, analysis, and feedback report.
RESULTS: After 3 Delphi rounds, consensus was achieved on the description,
symptoms, and diagnosis of CTS. The experts agreed that patients with CTS should
always be instructed, and instructions combined with splinting, corticosteroid
injection, corticosteroid injections plus splinting, and surgery are suitable
treatments for CTS. Relevant details for the use of instructions, splinting,
corticosteroid injections, and surgery were described. Main factors for selecting
one of the aforementioned treatment options were identified as follows: severity
and duration of the disorder and previous treatments received. A relation between
the severity/duration and choice of therapy was found by the experts and reported
in the guideline. CONCLUSIONS: This multidisciplinary treatment guideline may
help physicians and allied health care professionals to provide patients with CTS
with the most effective and efficient treatment available.
PMID- 25128001
TI - Polymorphisms in estrogen receptors predict the risk of male infertility: a meta
analysis.
AB - BACKGROUND: Estrogen receptors play an important role in mediating estrogen
action on target tissues, and the estrogen is relevant to male infertility.
Single nucleotide polymorphisms (SNPs) in estrogen receptors may be associated
with the risk of male infertility. A variety of case control studies have been
published evaluating this association. However, the accumulated studies have
shown inconsistent conclusions. METHODS: To further determine the potential
association between the four common SNPs (rs2234693, rs9340799, rs1256049 and
rs4986938) in estrogen receptors gene and male infertility, this meta-analysis
was performed according to the 10 published case control studies. The odds ratio
(OR) and 95% confidence interval (CI) were used to evaluate the strength of the
associations. RESULTS: It was revealed that the sub-group analysis by the
ethnicity, for the rs2234693, a significant association in the comparison of CC
vs. TT (OR = 0.61, 95% CI: 0.40-0.93), CT vs. TT (OR = 0.67, 95% CI: 0.49-0.93)
and CC + CT vs. TT (OR = 0.66, 95% CI: 0.49-0.89) in the Asian population with
male infertility. For rs9340799 polymorphism, increased risks were observed for
the comparison of AA vs. GG (OR = 1.75, 95% CI: 1.15-2.68) and AA vs. GA + GG (OR
= 1.38, 95% CI: 1.02-1.88). For rs1256049 polymorphism, the comparison of the GA
vs. GG (OR = 1.52, 95% CI: 1.00-2.31) and AA + GA vs. GG (OR = 1.74, 95% CI: 1.03
2.94), also increased risks present in Asian and Caucasian population,
respectively. CONCLUSIONS: The rs2234693C allele was associated with the
decreased risk for male infertility; however, the rs9340799AA genotype and the
rs1256049GA genotype were associated with an increased risk for male infertility.
PMID- 25128002
TI - Effect of electroacupuncture versus pelvic floor muscle training plus solifenacin
for moderate and severe mixed urinary incontinence in women: a study protocol.
AB - BACKGROUND: In women with mixed urinary incontinence, pelvic floor muscle
training and solifenacin is the recommended conservative treatment, while
electroacupuncture is a safe, economical and effective option. METHODS/DESIGN: In
this prospective, multi-center, randomized controlled trial, five hundred women
with mixed urinary incontinence, from 10 centers will be randomized to receive
either electroacupuncture or pelvic floor muscle training plus solifenacin. Women
in the acupuncture group will receive electroacupuncture for 3 sessions per week,
over 12 weeks, while women in the control group will receive pelvic floor muscle
training plus solifenacin (5 mg once daily) for 36 weeks. The primary outcome
measure is the proportion of change in 72-hour incontinence episode frequency
from baseline to week 12. The secondary outcome measures include eleven items,
including proportion of participants with >=50% decrease in average 72-h
incontinence episode frequency, change from baseline in the amount of urine
leakage and proportion of change from baseline in 72-h incontinence episode
frequency in week 25-36, and so forth. Statistical analysis will include
covariance analysis, nonparametric tests and t tests. DISCUSSION: The objective
of this trial is to compare the efficacy and safety of electroacupuncture versus
pelvic floor muscle training plus solifenacin in women with moderate and severe
mixed urinary incontinence. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
NCT02047032.
PMID- 25128004
TI - Relating therapy for voices (the R2V study): study protocol for a pilot
randomized controlled trial.
AB - BACKGROUND: Evidence exists for the effectiveness of cognitive behaviour therapy
for psychosis with moderate effect sizes, but the evidence for cognitive
behaviour therapy specifically for distressing voices is less convincing. An
alternative symptom-based approach may be warranted and a body of literature has
explored distressing voices from an interpersonal perspective. This literature
has informed the development of relating therapy and findings from a case series
suggested that this intervention was acceptable to hearers and therapists.
METHODS/DESIGN: An external pilot randomized controlled trial (RCT) comparing
outcomes for 15 patients receiving 16 hours (weekly sessions of one hour) of
relating therapy and their usual treatment with 15 patients receiving only their
usual treatment. Participants will be assessed using questionnaires at baseline,
16 weeks (post-intervention), and 36 weeks (follow-up). DISCUSSION: Expected
outcomes will include a refined study protocol and an estimate of the effect size
to inform the sample size of a definitive RCT. If evidence from a fully powered
RCT suggests that relating therapy is effective, the therapy will extend the
range of evidence-based psychological therapies available to people who hear
distressing voices. TRIAL REGISTRATION: Current Controlled Trials ISRCTN
registration number 44114663. Registered on 13 June 2013.
PMID- 25128003
TI - Urine YKL-40 is associated with progressive acute kidney injury or death in
hospitalized patients.
AB - BACKGROUND: A translational study in renal transplantation suggested YKL-40, a
chitinase 3-like-1 gene product, plays an important role in acute kidney injury
(AKI) and repair, but data are lacking about this protein in urine from native
human kidneys. METHODS: This is an ancillary study to a single-center,
prospective observational cohort of patients with clinically-defined AKI
according to AKI Network serum creatinine criteria. We determined the association
of YKL -40 >= 5 ng/ml, alone or combined with neutrophil gelatinase-associated
lipocalin (NGAL), in urine collected on the first day of AKI with a clinically
important composite outcome (progression to higher AKI stage and/or in-hospital
death). RESULTS: YKL-40 was detectable in all 249 patients, but urinary
concentrations were considerably lower than in previously measured deceased-donor
kidney transplant recipients. Seventy-two patients (29%) progressed or died in
hospital, and YKL-40 >= 5 ng/ml had an adjusted odds ratio (95% confidence
interval) for the outcome of 3.4 (1.5-7.7). The addition of YKL-40 to a clinical
model for predicting the outcome resulted in a continuous net reclassification
improvement of 29% (P = 0.04). In patients at high risk for the outcome based on
NGAL concentrations in the upper quartile, YKL-40 further partitioned the cohort
into moderate-risk and very high-risk groups. CONCLUSIONS: Urine YKL-40 is
associated with AKI progression and/or death in hospitalized patients and
improves clinically determined risk reclassification. Combining YKL-40 with other
AKI biomarkers like NGAL may further delineate progression risk, though
additional studies are needed to determine whether YKL-40 has general
applicability and to define its association with longer-term outcomes in AKI.
PMID- 25128005
TI - The effects of immunotherapy with intravenous immunoglobulins versus no
intervention, placebo, or usual care in patients with recurrent miscarriages: a
protocol for a systematic review with meta-analyses, trial sequential analyses,
and individual patient data meta-analyses of randomised clinical trials.
AB - BACKGROUND: Recurrent miscarriage is generally defined as three or more
miscarriages before gestational week 20. Recurrent miscarriage affects 1% of all
women and the condition can only be explained by parental chromosome
abnormalities, uterine malformations, or endocrine or thrombophilic disturbances
to a limited extent. Immunological disturbances are hypothesised to play an
important role in recurrent miscarriage and, therefore, various types of
immunologically-based therapies have been tested in recurrent miscarriage
patients including intravenous immunoglobulins. So far, at least eight randomised
placebo-controlled trials, with opposing results, investigating intravenous
immunoglobulins with a total of 324 recurrent miscarriage patients have been
published. METHODS/DESIGN: We will include randomised clinical trials
irrespective of publication date, publication type, publication language, and
publication status investigating infusions with immunoglobulins in relation to
pregnancy compared to placebo, no intervention, or treatment as usual for
assessments of benefits and harms. The relevant published literature will be
searched using the following databases: Cochrane Central Register of Controlled
Trials, Medline, Embase, WHO International Clinical Trials Registry Platform, and
Ovid Medline In-Process and Other Non-Indexed Citations databases. Two review
authors will independently extract data and assess risk of bias. We will
undertake meta-analyses according to the recommendations stated in the Cochrane
Handbook for Systematic Reviews of Interventions. Further, we will conduct trial
sequential analyses and individual patient data meta-analyses. DISCUSSION: A
miscarriage results in great sorrow, loss of life quality, and personal concern.
In particular, recurrent miscarriage is extremely stressful and burdensome. It
is, therefore, very important to conduct research in this area. There is
currently no evidence-based treatment for women with recurrent miscarriage which
significantly improves their ability to give live birth. Therefore, a
comprehensive up-to-date systematic review is needed. By using individual patient
data, it will be possible to provide new knowledge about the benefits and harms
of intravenous immunoglobulins and try to identify the subgroup in which the
treatment will have the highest impact.This systematic review protocol was
registered within the International Prospective Register of Systematic Reviews
(PROSPERO) as number CRD42014007112.
PMID- 25128007
TI - Does intravenous magnesium reduce the need for hospital admission among adult
patients with acute asthma exacerbations?
PMID- 25128006
TI - [Sudden cardiac death in individuals with normal hearts: an update].
AB - Sudden death (SD) is a tragic event and a world-wide health problem. Every year,
near 4-5 million people experience SD. SD is defined as the death occurred in 1h
after the onset of symptoms in a person without previous signs of fatality. It
can be named "recovered SD" when the case received medical attention, cardiac
reanimation effective defibrillation or both, surviving the fatal arrhythmia.
Cardiac channelopathies are a group of diseases characterized by abnormal ion
channel function due to genetic mutations in ion channel genes, providing
increased susceptibility to develop cardiac arrhythmias and SD. Usually the death
occurs before 40 years of age and in the autopsy the heart is normal. In this
review we discuss the main cardiac channelopathies involved in sudden cardiac
death along with current management of cases and family members that have
experienced such tragic event.
PMID- 25128008
TI - Emergency care and the national quality strategy: highlights from the Centers for
Medicare & Medicaid Services.
AB - The Centers for Medicare & Medicaid Services (CMS) of the US Department of Health
and Human Services seeks to optimize health outcomes by leading clinical quality
improvement and health system transformation through a variety of activities,
including quality measure alignment, prioritization, and implementation. CMS
manages more than 20 federal quality measurement and public reporting programs
that cover the gamut of health care providers and facilities, including both
hospital-based emergency departments (EDs) and individual emergency physicians.
With more than 130 million annual visits, and as the primary portal of hospital
admission, US hospital-based EDs deliver a substantial portion of acute care to
Medicare beneficiaries. Given the position of emergency care across clinical
conditions and between multiple settings of care, the ED plays a critical role in
fulfilling all 6 priorities of the National Quality Strategy. We outline current
CMS initiatives and future opportunities for emergency physicians and EDs to
effect each of these priorities and help CMS achieve the triple aim of better
health, better health care, and lower costs.
PMID- 25128009
TI - Advancing regulatory science to bring novel medical devices for use in emergency
care to market: the role of the Food and Drug Administration.
AB - The Food and Drug Administration (FDA) performs regulatory science to provide
science-based medical product regulatory decisions. This article describes the
types of scientific research the FDA's Center for Devices and Radiological Health
performs and highlights specific projects related to medical devices for
emergency medicine. In addition, this article discusses how results from
regulatory science are used by the FDA to support the regulatory process as well
as how the results are communicated to the public. Regulatory science supports
the FDA's mission to assure safe, effective, and high-quality medical products
are available to patients.
PMID- 25128010
TI - Acute HIV infection and implications of fourth-generation HIV screening in
emergency departments.
PMID- 25128011
TI - A cross-sectional retrospective analysis of the regionalization of complex
surgery.
AB - BACKGROUND: The Veterans Health Administration (VHA) system has assigned a
surgical complexity level to each of its medical centers by specifying
requirements to perform standard, intermediate or complex surgical procedures. No
study to similarly describe the patterns of relative surgical complexity among a
population of United States (U.S) civilian hospitals has been completed. METHODS:
DESIGN: single year, retrospective, cross-sectional. SETTING/PARTICIPANTS: the
study used Florida Inpatient Discharge Data from short-term acute hospitals for
calendar year 2009. Two hundred hospitals with 2,542,920 discharges were
organized into four quartiles (Q 1, 2, 3, 4) based on the number of complex
procedures per hospital. The VHA surgical complexity matrix was applied to assign
relative complexity to each procedure. The Clinical Classification Software (CCS)
system assigned complex procedures to clinically meaningful groups. For outcome
comparisons, propensity score matching methods adjusted for the surgical
procedure, age, gender, race, comorbidities, mechanical ventilator use and type
of admission. MAIN OUTCOME MEASURES: in-hospital mortality and length-of-stay
(LOS). RESULTS: Only 5.2% of all inpatient discharges involve a complex
procedure. The highest volume complex procedure hospitals (Q4) have 49.8% of all
discharges but 70.1% of all complex procedures. In the 133,436 discharges with a
primary complex procedure, 374 separate specific procedures are identified, only
about one third of which are performed in the lowest volume complex procedure
(Q1) hospitals. Complex operations of the digestive, respiratory, integumentary
and musculoskeletal systems are the least concentrated and proportionately more
likely to occur in the lower volume hospitals. Operations of the cardiovascular
system and certain technology dependent miscellaneous diagnostic and therapeutic
procedures are the most concentrated in high volume hospitals. Organ transplants
are only done in Q4 hospitals. There were no significant differences in in
hospital mortality rates and the longest lengths of stay were found in higher
volume hospitals. CONCLUSIONS: Complex surgery in Florida is effectively
regionalized so that small volume hospitals operating within the range of complex
procedures appropriate to their capabilities provide no increased risk of post
surgical mortality.
PMID- 25128013
TI - Denosumab for the management of hypercalcemia of malignancy in patients with
multiple myeloma and renal dysfunction.
PMID- 25128012
TI - Pumping iron.
AB - The primary role of the ZIP13 metal transporter in flies is to move iron ions out
of cells, rather than moving zinc ions into cells, as is the case in human cells.
PMID- 25128014
TI - The impact of preoperative patient characteristics on the cost-effectiveness of
total hip replacement: a cohort study.
AB - BACKGROUND: To facilitate the discussion on the increasing number of total hip
replacements (THR) and their effectiveness, we apply a joint evaluation of
hospital case costs and health outcomes at the patient level to enable
comparative effectiveness research (CER) based on the preoperative health state.
METHODS: In 2012, 292 patients from a German orthopedic hospital participated in
health state evaluation before and 6 months after THR, where health-related
quality of life (HRQoL) and disease specific pain and dysfunction were analyzed
using EQ-5D and WOMAC scores. Costs were measured with a patient-based DRG
costing scheme in a prospective observation of a cohort. Costs per quality
adjusted life year (QALY) were calculated based on the preoperative WOMAC score,
as preoperative health states were found to be the best predictors of QALY gains
in multivariate linear regressions. RESULTS: Mean inpatient costs of THR were
6,310 Euros for primary replacement and 7,730 Euros for inpatient lifetime costs
including revisions. QALYs gained using the U.K. population preference-weighted
index were 5.95. Lifetime costs per QALY were 1,300 Euros. CONCLUSIONS: The WOMAC
score and the EQ-5D score before operation were the most important predictors of
QALY gains. The poorer the WOMAC score or the EQ-5D score before operation, the
higher the patient benefit. Costs per QALY were far below common thresholds in
all preoperative utility score groups and with all underlying calculation
methodologies.
PMID- 25128015
TI - Transcriptome sequencing and analysis of the zoonotic parasite Spirometra
erinacei spargana (plerocercoids).
AB - BACKGROUND: Although spargana, which are the plerocercoids of Spirometra
erinacei, are of biological and clinical importance, expressed sequence tags
(ESTs) from this parasite have not been explored. To understand molecular and
biological features of this parasite, sparganum ESTs were examined by large-scale
EST sequencing and multiple bioinformatics tools. METHODS: Total RNA was isolated
from spargana and then ESTs were generated, assembled and sequenced. Many
biological aspects of spargana were investigated using multi-step bioinformatics
tools. RESULTS: A total of 5,634 ESTs were collected from spargana. After
clustering and assembly, the functions of 1,794 Sparganum Assembled ESTs (SpAEs)
including 934 contigs and 860 singletons were analyzed. A total of 1,351 (75%)
SpAEs were annotated using a hybrid of BLASTX and InterProScan. Of these genes,
1,041 (58%) SpAEs had high similarity to tapeworms. In the context of the biology
of sparganum, our analyses reveal: (i) a highly expressed fibronectin 1, a
ubiquitous and abundant glycoprotein; (ii) up-regulation of enzymes related with
glycolysis pathway; (iii) most frequent domains of protein kinase and RNA
recognition motif domain; (iv) a set of helminth-parasitic and spargana-specific
genes that may offer a number of antigen candidates. CONCLUSIONS: Our
transcriptomic analysis of S. erinacei spargana demonstrates biological aspects
of a parasite that invades and travels through subcutaneous tissue in
intermediate hosts. Future studies should include comparative analyses using
combinations of transcriptome and proteome data collected from the entire life
cycle of S. erinacei.
PMID- 25128016
TI - Recombinant activated factor VIIa to treat refractory lower gastrointestinal
hemorrhage in a patient with recently implanted mechanical valve: a case report.
AB - BACKGROUND: Bleeding is a common complication after cardiac surgery. However,
lower gastrointestinal bleeding is not usually associated with this type of
surgery. CASE PRESENTATION: A 50-year-old man with a history of aortic
regurgitation underwent elective mechanical valve replacement under
cardiopulmonary bypass. He experienced a complicated intraoperative course
involving unexplained cardiac arrest following induction of anesthesia. He also
developed two episodes of massive lower gastrointestinal bleeding secondary to
mucosal ischemia while convalescing in the cardiothoracic surgery intensive care
unit. After unsuccessful attempts to control the bleeding, exhaustion of blood
products, and consideration of the high risk of mortality associated with surgery
and the possibility of early- and long-term surgical complications, the decision
was made to administer two successive doses of recombinant activated factor VII
at 60 mcg/kg. Hemostasis was achieved without adverse systemic or valvular
effects. CONCLUSIONS: A favorable outcome was achieved after administration of
recombinant activated factor VII, which controlled the patient's severe lower
gastrointestinal bleeding. This outcome suggests the need to raise awareness
about the use of this drug in dire circumstances when other conventional measures
fail or are unsuitable.
PMID- 25128018
TI - Paroxysmal nocturnal hemoglobinuria in an 86 year old woman.
PMID- 25128017
TI - HiChIP: a high-throughput pipeline for integrative analysis of ChIP-Seq data.
AB - BACKGROUND: Chromatin immunoprecipitation (ChIP) followed by next-generation
sequencing (ChIP-Seq) has been widely used to identify genomic loci of
transcription factor (TF) binding and histone modifications. ChIP-Seq data
analysis involves multiple steps from read mapping and peak calling to data
integration and interpretation. It remains challenging and time-consuming to
process large amounts of ChIP-Seq data derived from different antibodies or
experimental designs using the same approach. To address this challenge, there is
a need for a comprehensive analysis pipeline with flexible settings to accelerate
the utilization of this powerful technology in epigenetics research. RESULTS: We
have developed a highly integrative pipeline, termed HiChIP for systematic
analysis of ChIP-Seq data. HiChIP incorporates several open source software
packages selected based on internal assessments and published comparisons. It
also includes a set of tools developed in-house. This workflow enables the
analysis of both paired-end and single-end ChIP-Seq reads, with or without
replicates for the characterization and annotation of both punctate and diffuse
binding sites. The main functionality of HiChIP includes: (a) read quality
checking; (b) read mapping and filtering; (c) peak calling and peak consistency
analysis; and (d) result visualization. In addition, this pipeline contains
modules for generating binding profiles over selected genomic features, de novo
motif finding from transcription factor (TF) binding sites and functional
annotation of peak associated genes. CONCLUSIONS: HiChIP is a comprehensive
analysis pipeline that can be configured to analyze ChIP-Seq data derived from
varying antibodies and experiment designs. Using public ChIP-Seq data we
demonstrate that HiChIP is a fast and reliable pipeline for processing large
amounts of ChIP-Seq data.
PMID- 25128020
TI - Monolithic superelastic rods with variable flexural stiffness for spinal fusion:
modeling of the processing-properties relationship.
AB - The concept of a monolithic Ti-Ni spinal rod with variable flexural stiffness is
proposed to reduce the risks associated with spinal fusion. The variable
stiffness is conferred to the rod using the Joule-heating local annealing
technique. The annealing temperature and the mechanical properties' distributions
resulted from this thermal treatment are numerically modeled and experimentally
measured. To illustrate the possible applications of such a modeling approach,
two case studies are presented: (a) optimization of the Joule-heating strategy to
reduce annealing time, and (b) modulation of the rod's overall flexural stiffness
using partial annealing. A numerical model of a human spine coupled with the
model of the variable flexural stiffness spinal rod developed in this work can
ultimately be used to maximize the stabilization capability of spinal
instrumentation, while simultaneously decreasing the risks associated with spinal
fusion.
PMID- 25128019
TI - The cytokines within the carotid plaque in symptomatic patients with internal
carotid artery stenosis.
AB - The aim of the study was the evaluation of the inflammatory cytokines within
atheromatic carotid plaque. MATERIALS AND METHODS: The experiment was carried out
on 100 symptomatic patients with internal carotid artery stenosis that underwent
carotid endarterectomy. Every patient had the wall of the carotid artery resected
during organ harvesting surgery in order to evaluate some cytokines (TGF-beta,
VEGF, FGF, TNF-alpha) and to perform the immunohistochemistry (IHC). An
immunoreactive score (IRS) was calculated based on the staining intensity and the
number of cells stained. Over a 3-year period, 7 patients died, and 2 patients
were lost to follow-up. The study group consisted of 91 patients. The control
group comprised 20 young organ donors with confirmed death brain, who had their
normal carotid artery sampled. RESULTS: In all healthy donors (control group)
with normal carotid arteries the three cytokines (TGF-beta, VEGF, TNF-alpha) were
not discovered. The presence of FGF was confirmed in 25% of healthy donors,
probably due to an intima fibroblasts activity, responsible for the synthesis of
elastin and collagen to the extracellular matrix (ECM). Only three cytokines (TGF
beta, FGF, TNF-alpha) were found within atheromatous plaques (study group).
CONCLUSIONS: Our research confirmed that these factors may accelerate the
development of atheromatic plaque and its destabilisation.
PMID- 25128021
TI - "You need to take care of it like you take care of your soul": perceptions and
behaviours related to mosquito net damage, care, and repair in Senegal.
AB - BACKGROUND: Net care and repair behaviours are essential for prolonging the
durability of long-lasting insecticidal nets. Increased net durability has
implications for protection against malaria as well as cost savings from less
frequent net distributions. This study investigated behaviours and motivations
for net care and repair behaviours in Senegal with the aim of informing social
and behaviour change communication (SBCC) programmes, using the Health Belief
Model as a framework. METHODS: Data were collected from 114 participants in eight
regions of Senegal. Participants were eligible for the study if they were at
least 18 years old and if their household owned at least one net. These
respondents included 56 in-depth interview respondents and eight focus groups
with 58 participants. In addition, the qualitative data were supplemented with
observational questionnaire data from a total of 556 sleeping spaces. Of these
spaces, 394 had an associated net. RESULTS: Reported net care and repair
behaviours and motivations varied substantially within this sample. Children and
improper handling were seen as major sources of net damage and respondents often
tried to prevent damage by storing nets when not in use. Washing was seen as an
additional method of care, but practices for washing varied and may have been
damaging to nets in some cases. Participants mentioned a sense of pride of having
a net in good condition and the uncertainty around when they could expect another
net distribution as motivations for net care. Net repair appeared to be a less
common behaviour and was limited by the perspective that net degradation was
inevitable and that repairs themselves could weaken nets. CONCLUSION: These
findings can be understood using the Health Belief Model framework of perceived
severity, perceived susceptibility, perceived barriers, perceived benefits, self
efficacy, and cues to action. This model can guide SBCC messages surrounding net
care and repair to promote practices associated with net longevity. Such messages
should promote the benefits of intact nets and provide tools for overcoming
barriers to care and repair.
PMID- 25128022
TI - Citrate anticoagulation versus systemic heparinisation in continuous venovenous
hemofiltration in critically ill patients with acute kidney injury: a multi
center randomized clinical trial.
AB - INTRODUCTION: Because of ongoing controversy, renal and vital outcomes are
compared between systemically administered unfractionated heparin and regional
anticoagulation with citrate-buffered replacement solution in predilution mode,
during continuous venovenous hemofiltration (CVVH) in critically ill patients
with acute kidney injury (AKI). METHODS: In this multi-center randomized
controlled trial, patients admitted to the intensive care unit requiring CVVH and
meeting inclusion criteria, were randomly assigned to citrate or heparin. Primary
endpoints were mortality and renal outcome in intention-to-treat analysis.
Secondary endpoints were safety and efficacy. Safety was defined as absence of
any adverse event necessitating discontinuation of the assigned anticoagulant.
For efficacy, among other parameters, survival times of the first hemofilter were
studied. RESULTS: Of the 139 patients enrolled, 66 were randomized to citrate and
73 to heparin. Mortality rates at 28 and 90 days did not differ between groups:
22/66 (33%) of citrate-treated patients died versus 25/72 (35%) of heparin
treated patients at 28 days, and 27/65 (42%) of citrate-treated patients died
versus 29/69 (42%) of heparin-treated patients at 90 days (P = 1.00 for both).
Renal outcome, i.e. independency of renal replacement therapy 28 days after
initiation of CVVH in surviving patients, did not differ between groups: 29/43
(67%) in the citrate-treated patients versus 33/47 (70%) in heparin-treated
patients (P = 0.82). Heparin was discontinued in 24/73 (33%) of patients whereas
citrate was discontinued in 5/66 (8%) of patients (P < 0.001). Filter survival
times were superior for citrate (median 46 versus 32 hours, P = 0.02), as were
the number of filters used (P = 0.002) and the off time within 72 hours (P =
0.002). The costs during the first 72 hours of prescribed CVVH were lower in
citrate-based CVVH. CONCLUSIONS: Renal outcome and patient mortality were similar
for citrate and heparin anticoagulation during CVVH in the critically ill patient
with AKI. However, citrate was superior in terms of safety, efficacy and costs.
TRIAL REGISTRATION: Clinicaltrials.gov NCT00209378. Registered 13th September
2005.
PMID- 25128023
TI - A longitudinal study investigating quality of life and nutritional outcomes in
advanced cancer patients receiving home parenteral nutrition.
AB - BACKGROUND: In cancer patients where gastrointestinal function is marginal and
malnutrition significant enough to result in the requirement for intensive
nutrition support, parenteral nutrition (PN) is indicated. This longitudinal
study examined the quality of life (QoL) and nutritional outcomes in advanced
cancer patients receiving home PN (HPN). METHODS: Fifty-two adult cancer patients
(21 males, 31 females, average age 53 years) treated at a specialized cancer
facility between April 2009 and November 2011 met criteria. QoL and nutritional
status were measured at baseline and every month while on HPN using EORTC-QLQ
C30, Karnofsky Performance Status (KPS), and Subjective Global Assessment (SGA).
Repeated measures ANOVA and Generalized Estimating Equations (GEE) were used to
evaluate longitudinal changes in QoL and SGA. RESULTS: Cancer diagnoses included
pancreatic (n = 14), colorectal (n = 11), ovarian (n = 6), appendix (n = 5),
stomach (n = 4) and others (n = 12). Average weight loss 6-months prior to HPN
was 13.2 kg (16.9%). Average weight at initiation of HPN was 62.2 kg. In patients
with available follow-up data after 1 month (n = 39), there was a significant
improvement in SGA, weight (61.5 to 63.1 kg; p = 0.03) and KPS (61.6 to 67.3; p =
0.01) from baseline. Similarly, after 2 months (n = 22), there was an improvement
in global QoL (37.1 to 49.2; p = 0.02), SGA, weight (57.6 to 60 kg; p = 0.04) and
KPS (63.2 to 73.2; p = 0.01) from baseline. Finally, after 3 months (n = 15),
there was an improvement in global QoL (30.6 to 54.4; p = 0.02), SGA, weight
(61.1 to 65.9 kg; p = 0.04) and KPS (64.0 to 78.7; p = 0.002) from baseline. Upon
GEE analysis, every 1 month of HPN was associated with an increase of 6.3 points
in global QoL (p<0.001), 1.3 kg in weight (p = 0.009) and 5.8 points in KPS
(p<0.001). CONCLUSIONS: HPN is associated with an improvement in QoL, KPS and
nutritional status in advanced cancer patients, irrespective of their tumor type,
who have compromised enteral intake and malnutrition. The greatest benefit was
seen in patients with 3 months of HPN, although patients receiving HPN for 1 or 2
months also demonstrated significant improvements.
PMID- 25128024
TI - The association between air pollutants and morbidity for diabetes and liver
diseases modified by sexes, ages, and seasons in Tianjin, China.
AB - With the generalized linear model and natural splines (ns), we examined the
association between outdoor air pollutants and daily morbidity for diabetes and
liver disease stratified by sexes and ages based on 4 years of daily data (2008
2011) in Tianjin, China. Season effects of air pollutants including particulate
matter (PM), sulfur dioxide (SO2), and nitrogen dioxide (NO2) were also
investigated. An increase of 10 MUg/m(3) in a 2-day average concentrations of
particulate matter with diameters of 10 MUm or less (PM10), SO2, and NO2
corresponds to increases in diabetes morbidity of 0.39 % (95 % confidence
interval (CI), -0.42-1.12), 0.15 % (95 % CI, -0.25-0.54), and 1.22 % (95 % CI,
0.51-2.96), respectively. As for liver morbidity, the increases were -0.84 % (95
% CI, -2.33-0.62), 0.90 % (95 % CI, 0.50-1.74), and 1.10 % (95 % CI, -2.58-4.78),
respectively. The effects were stronger in the cool season than those in the warm
season; females and the elderly were generally more vulnerable to outdoor air
pollution. This study possesses scientific implications and instructional
significance for local environmental standards and medical policymaking.
PMID- 25128025
TI - Enhanced amyloidogenic processing of amyloid precursor protein and cell death
under prolonged endoplasmic reticulum stress in brain endothelial cells.
AB - Cerebral amyloid angiopathy resulting from the deposition of misfolded amyloid
beta (Abeta) peptide in the walls of brain's blood vessels is exhibited by the
majority of Alzheimer's disease (AD) patients, suggesting that alterations in
protein quality control contribute to AD-associated vascular dysfunction. The
present work addressed the role of ER stress in the amyloidogenic amyloid
precursor protein (APP) processing and subsequent Abeta generation in brain
endothelial cells (ECs). For that purpose, the RBE4 cell line was exposed to the
classical ER stressors thapsigargin or brefeldin A to mimic the altered ER
homeostasis observed in AD. In treated cells, an increase in the levels of
markers of ER stress (XBP1 and GRP78) and of the ER stress-induced apoptotic
pathway (caspase-12, JNK, and CHOP) was observed concomitantly with the
accumulation of reactive oxygen species. Under these conditions, a significant ER
to-mitochondria Ca(2+) transfer was also found, which culminated in mitochondrial
Ca(2+) overload and activation of mitochondria-dependent apoptosis. Moreover, it
was showed that prolonged ER stress induces intracellular APP accumulation, which
colocalizes with the ER chaperone GRP78, and activation of beta-secretase,
leading to increased intracellular Abeta levels, together with a decrease in
secreted Abeta. Finally, it was demonstrated that ER stress-induced changes in
Abeta levels and apoptotic cell death can be ameliorated by a blocker of the
mitochondrial Bax channel. These observations suggest that chronic ER stress
triggers APP accumulation in early comportments along the secretory pathway in
brain ECs and increases its amyloidogenic processing and Abeta generation leading
to apoptotic cell death.
PMID- 25128026
TI - Soluble Epoxide Hydrolase Deficiency or Inhibition Attenuates MPTP-Induced
Parkinsonism.
AB - Soluble epoxide hydrolase (sEH) inhibition has been demonstrated to have
beneficial effects on various diseases, such as hypertension, diabetes, and brain
ischemia. However, whether sEH inhibition has therapeutic potential in
Parkinson's disease is still unknown. In this paper, we found that sEH expression
is increased in 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP)-treated
mice, and sEH deficiency and inhibition significantly attenuated tyrosine
hydroxylase (TH)-positive cell loss and improved rotarod performance. The
substrate of sEH, 14,15-epoxyeicosatrienoic acid (14,15-EET), protected TH
positive cells and alleviated the rotarod performance deficits of wild-type mice
but not sEH-knockout mice. Moreover, the 14,15-EET antagonist 14,15-epoxyeicosa
5(Z)-enoic acid (14,15-EEZE) abolished the neuronal protective effects of sEH
deficiency. In primary cultured cortical neurons, MPP(+) induced significant Akt
inactivation in neurons from sEH wild-type mice, and this effect was not observed
in neurons from knockout mice. Our data indicate that sEH deficiency and
inhibition increased 14,15-EET in MPTP-treated mice, which activated the Akt
mediated protection of TH-positive neurons and behavioral functioning. We also
found that sEH deficiency attenuated TH-positive cell loss in a paraquat-induced
mouse model of Parkinson's. Our data suggest that sEH inhibition might be a
powerful tool to protect dopaminergic neurons in Parkinson's disease.
PMID- 25128027
TI - Attenuated Blood-Brain Barrier Dysfunction by XQ-1H Following Ischemic Stroke in
Hyperlipidemic Rats.
AB - Following ischemic stroke, blood-brain barrier (BBB) is disrupted and is further
aggravated with the corresponding incidence of hyperlipidemia. BBB breakdown
promotes inflammation infiltration into the brain, which exacerbates cerebral
ischemic injury as a result. Here, we report that 10-O-(N,N-dimethylaminoethyl)
ginkgolide B methanesulfonate (XQ-1H), a novel analog of ginkgolide B, alleviates
BBB breakdown in hyperlipidemic rats and protects endothelial cells against
inflammatory response. Middle cerebral artery occlusion (MCAO) modeled ischemic
stroke in rats. Before surgery, these rats were fed a cholesterol-rich diet to
induce an experimental hyperlipidemic condition. Additionally, lipopolysaccharide
(LPS) incubation with rat brain microvessel endothelial cells (rBMECs) was
applied to mimic hyperlipidemia-induced inflammatory injury of BBB. The results
indicated more severe infarct size, increased BBB permeability, excessive
secretion of pro-inflammatory cytokines, and exaggerated inflammation
infiltration of the brain in hyperlipidemic rats following MCAO when compared to
rats fed with normal diet. XQ-1H protected BBB integrity, lessoned brain edema
and inflammation penetration, downregulated MMP-9 and VCMA-1 expressions, and
extenuated ischemic infarction. XQ-1H alleviated LPS-induced inflammatory
response in rBMECs, characterized by promoting cell viability, inhibiting TNF
alpha, IL-1beta, and IL-6 releasing, and downregulating NF-kappaB inflammatory
signal and downstream proteins, such as VCAM-1 and iNOS. In conclusion, the
present study shows that XQ-1H stabilizes BBB function following ischemic stroke
in hyperlipidemic rats, and the possible mechanisms may be related to
inflammation inhibition.
PMID- 25128028
TI - AP-1/sigma1B-Dependent SV Protein Recycling Is Regulated in Early Endosomes and
Is Coupled to AP-2 Endocytosis.
AB - Adaptor protein (AP)-1/sigma1B(-/-) mice have reduced synaptic-vesicle (SV)
recycling and increased endosomes. Mutant mice have impaired spatial memory, and
sigma1B-deficient humans have a severe mental retardation. In order to define
these sigma1B(-/-) 'bulk' endosomes and to determine their functions in SV
recycling, we developed a protocol to separate them from the majority of the
neuronal endosomes. The sigma1B(-/-) 'bulk' endosomes proved to be classic early
endosomes with an increase in the phospholipid phosphatidylinositol 3-phosphate
(PI-3-P), which recruits proteins mediating protein sorting out of early
endosomes into different routes. sigma1B deficiency induced alterations in the
endosomal proteome reveals two major functions: SV protein storage and sorting
into endolysosomes. Alternative endosomal recycling pathways are not up
regulated, but certain SV proteins are misrouted. Tetraspanins are enriched in
sigma1B(-/-) synaptosomes, but not in their endosomes or in their clathrin-coated
vesicles (CCVs), indicating AP-1/sigma1B-dependent sorting. Synapses contain also
more AP-2 CCV, although it is expected that they contain less due to reduced SV
recycling. Coat composition of these AP-2 CCVs is altered, and thus, they
represent a subpopulation of AP-2 CCVs. Association of calmodulin-dependent
protein kinase (CaMK)-IIalpha, -delta and casein kinase (CK)-IIalpha with the
endosome/SV pool is altered, as well as 14-3-3eta, indicating changes in specific
signalling pathways regulating synaptic plasticity. The accumulation of early
endosomes and endocytotic AP-2 CCV indicates the regulation of SV recycling via
early endosomes by the interdependent regulation of AP-2-mediated endocytosis and
AP-1/sigma1B-mediated SV reformation.
PMID- 25128029
TI - Memory Impairment in Estrogen Receptor alpha Knockout Mice Through Accumulation
of Amyloid-beta Peptides.
AB - Estrogen has been known to reduce the development of Alzheimer's disease (AD).
However, exact mechanisms are not clear. We investigated whether estrogen can
increase amyloid-beta (Abeta) degradation and affects Abeta-induced memory
impairment in an estrogen deficiency model. Estrogen receptor alpha (ERalpha)
knockout mice and wild-type mice were intracerebroventricular (ICV) infused with
Abeta (300 pmol) for 2 weeks. Cognitive function was then assessed by the Morris
water maze test and passive avoidance test. In addition, Western blot analysis,
immunostaining, immunofluorescence staining, ELISA, and enzyme activity assays
were used to examine the degree of Abeta deposition in the brains of ERalpha
knockout mice. In our present study, Abeta was accumulated more in the ERalpha
knockout mice brain and greatly worsened memory impairment and glial activation
as well as neurogenic inflammation. These results suggest that estrogen may
protect memory impairment by stimulating the degradation of Abeta and down
regulate neurogenic inflammation as well as amyloidogenesis.
PMID- 25128032
TI - Re: risk factors for umbilical trocar site incisional hernia in laparoscopic
cholecystectomy: a prospective 3-year follow-up study.
PMID- 25128031
TI - Plants and microbes assisted selenium nanoparticles: characterization and
application.
AB - Selenium is an essential trace element and is an essential component of many
enzymes without which they become inactive. The Se nanoparticles of varying shape
and size may be synthesized from Se salts especially selenite and selenates in
presence of reducing agents such as proteins, phenols, alcohols and amines. These
biomolecules can be used to reduce Se salts in vitro but the byproducts released
in the environment may be hazardous to flora and fauna. In this review,
therefore, we analysed in depth, the biogenic synthesis of Se nanoparticles,
their characterization and transformation into t- Se, m-Se, Se-nanoballs, Se
nanowires and Se-hollow spheres in an innocuous way preventing the environment
from pollution. Their shape, size, FTIR, UV-vis, Raman spectra, SEM, TEM images
and XRD pattern have been analysed. The weak forces involved in aggregation and
transformation of one nano structure into the other have been carefully resolved.
PMID- 25128033
TI - Difference of the associations between self-rated health and demographic
characteristics, lifestyle, and psychosocial work environment between two types
of Chinese worksite.
AB - BACKGROUND: Although studies of self-rated health (SRH) are conducted widely in
developed countries, comprehensive assessments of the determinants of SRH in
Chinese are scarce, particularly for working Chinese individuals. Determinants of
SRH might differ among worksites based on differences in the nature and stress
associated with different jobs, work intensity, and the lifestyles of employees.
METHODS: Two thousand and forty questionnaires that addressed SRH, demographic
characteristics, lifestyle, and the psychosocial work environment were
administered to employees at two worksites. A total of 1644 subjects provided
complete data for analysis (80.6% response rate). RESULTS: Participants from
government departments had significantly better SRH than did those from high-tech
enterprises (61.1% vs. 67.5%, respectively). Lifestyles were significantly less
healthy at government departments compared with high-tech enterprises, whereas
the psychosocial work environment was better. The results of unadjusted and
adjusted models revealed differences between the potential health-influencing
factors of participants based on their type of worksite. In logistic regression
models, gender was strongly associated with SRH in all participants, whereas
length of service was correlated with SRH only in participants from high-tech
enterprises. In high-tech enterprises, good SRH was less common in physically
inactive subjects vs. physically active participants (OR = 0.561). In government
departments, passive smoking was negatively associated with SRH significantly.
Social capital (OR = 1.073) and job control (OR = 1.550) were positively
correlated with SRH in high-tech enterprises. Job control was the only
psychosocial factor significantly associated with SRH in government departments.
CONCLUSIONS: Participants from different types of worksite reported different
SRH, healthy lifestyles, and psychosocial work environments. Moreover, the
association between SRH and demographic characteristics, lifestyle, and the
psychosocial work environment significantly differed by type of worksite.
PMID- 25128030
TI - Protective Effect of a cAMP Analogue on Behavioral Deficits and Neuropathological
Changes in Cuprizone Model of Demyelination.
AB - Multiple sclerosis (MS) is an inflammatory demyelinating disease that leads to
neuronal cell loss. Cyclic AMP and its analogs are well known to decrease
inflammation and apoptosis. In the present study, we examined the effects of
bucladesine, a cell-permeable analogue of cyclic adenosine monophosphate (cAMP),
on myelin proteins (PLP, PMP-22), inflammation, and apoptotic, as well as anti
apoptotic factors in cuprizone model of demyelination. C57BL/6J mice were fed
with chow containing 0.2% copper chelator cuprizone or vehicle by daily oral
gavage for 5 weeks to induce reversible demyelination predominantly of the corpus
callosum. Bucladesine was administered intraperitoneally at different doses
(0.24, 0.48, or 0.7 MUg/kg body weight) during the last 7 days of 5-week
cuprizone treatment. Bucladesine exhibited a protective effect on myelination.
Furthermore, bucladesine significantly decreased the production of interleukin-6
pro-inflammatory mediator as well as nuclear factor-kappaB activation and reduced
the mean number of apoptotic cells compared to cuprizone-treated mice.
Bucladesine also decreased production of caspase-3 as well as Bax and increased
Bcl-2 levels. Our data revealed that enhancement of intracellular cAMP prevents
demyelination and plays anti-inflammatory and anti-apoptotic properties in mice
cuprizone model of demyelination. This suggests the modulation of intracellular
cAMP as a potential target for treatment of MS.
PMID- 25128034
TI - Spatial epidemiology of dry eye disease: findings from South Korea.
AB - BACKGROUND: DED rate maps from diverse regions may allow us to understand world
wide spreading pattern of the disease. Only few studies compared the prevalence
of DED between geographical regions in non-spatial context. Therefore, we
examined the spatial epidemiological pattern of DED prevalence in South Korea
using a nationally representative sample. METHODS: We analyzed 16,431 Korean
adults aged 30 years or older of the 5th Korea National Health and Nutrition
Examination Survey. DED was defined as previously diagnosed by an ophthalmologist
as well as symptoms experienced. Multiple logistic regression analysis was used
to assess the spatial pattern in the prevalence of DED, and effects of
environmental factors. RESULTS: Among seven metropolitan cities and nine
provinces, three metropolitan cities located in the southeast of Korea revealed
the highest prevalence of DED. After adjusting for sex, age and survey year,
people living in urban areas had higher risk of having DED. Adjusted odds ratio
for having previously diagnosed DED was 1.677 (95% CI 1.299-2.166) for
metropolitan cities and 1.580 (95% CI 1.215-2.055) for other cities compared to
rural areas. Corresponding odds ratio for presenting DED symptoms was 1.388 (95%
CI 1.090-1.766) for metropolitan cities and 1.271 (95% CI 0.999-1.617) for other
cities. Lower humidity and longer sunshine duration were significantly associated
with DED. Among air pollutants, SO2 was associated with DED, while NO2, O3, CO,
and PM10 were not. CONCLUSION: Our findings suggest that prevalence of DED can be
affected by the degree of urbanization and environmental factors such as humidity
and sunshine duration.
PMID- 25128036
TI - Use of FRAX as a determinant for risk-based osteoporosis screening may decrease
unnecessary testing while improving the odds of identifying treatment candidates.
AB - PURPOSE: We have assessed the hypothetical impact of guideline-concordant
osteoporosis screening on baseline behaviors utilizing two different guidelines
and determined the relative ability of each to identify osteoporosis treatment
candidates. METHODS: We conducted secondary analyses from the Fracture Risk
Perception Study, which enrolled patients aged 50 to 75 years to complete
questionnaires about their bone health. We determined our baseline screening
rates and detection of treatment candidates and then assessed the hypothetical
impact of adherence to U.S. Preventive Services Task Force (USPSTF) and National
Osteoporosis Foundation (NOF) criteria, particularly for women aged 50 to 64.
RESULTS: Of 144 women aged 50 to 64 years screened, 14 (9.7%) were treatment
candidates. Screening based on identification of one or more risks (NOF) would
lead to testing of 102 of the 144 patients (71%) to identify 12 of 14 treatment
candidates (86%). Applying USPSTF criteria (9.3% FRAX threshold) would test 45 of
the same 144 women (31%) to identify 11 of 14 treatment candidates (79%). NOF
risk-based criteria would result in a moderate absolute screening rate reduction
(16%, p = .0011; 95% CI, 7%-25%), but only marginal improvement in identifying
treatment candidates (odds ratio, 2.67; 95% CI, 0.57-12.47). Applying the more
selective USPSTF criteria greatly reduced unnecessary testing (56% absolute
screening rate reduction; p < .0001; 95% CI, 47%-64%) while further improving the
odds of identifying treatment candidates (odds ratio, 10.35; 95% CI, 2.72-39.35).
CONCLUSIONS: When contemplating screening younger patients, systematic
calculation of FRAX and ordering only when the 9.3% fracture risk threshold is
reached may decrease unnecessary screening for many women while still identifying
appropriate osteoporosis treatment candidates.
PMID- 25128037
TI - Making the most of the Affordable Care Act's contraceptive coverage mandate for
privately-insured women.
PMID- 25128035
TI - "When you get old like this ... you don't run those risks anymore": influence of
age on sexual risk behaviors and condom use attitudes among methamphetamine-using
heterosexual women with a history of partner violence.
AB - BACKGROUND: Drug use and partner violence affect older women, yet few studies
highlight age-specific HIV risks and prevention strategies. This study compares
sexual risk behaviors, condom use attitudes, and HIV knowledge between
midlife/older women (ages 45+) and younger women (ages 18-44) reporting
methamphetamine use and partner violence in San Diego, California. METHODS: Our
mixed methods study used themes from a qualitative substudy (n = 18) to inform
logistic regression analysis of baseline data from an HIV behavioral intervention
trial (n = 154). FINDINGS: Age-related qualitative themes included physiologic
determinants, HIV knowledge, and "dodging the bullet," referring to a lifetime of
uncertainty surrounding HIV serostatus after engaging in unsafe drug and sex
practices. Midlife/older age was associated with never being married (24.2% vs.
51.2; p = .03), having less than a high school education/GED (12.1% vs. 34.7%; p
= .04), lower condom use self-efficacy (2.87 vs. 3.19; p = .03), lower positive
outcome expectancies (1.9 vs. 2.1; p = .04), and lower HIV knowledge (85.3% vs.
89.7%; p = .04); however, sexual risk behaviors were not associated with age
group. In the multivariate analysis, midlife/older age remained independently
associated with lower condom use self-efficacy (adjusted odds ratio, 0.49; 95%
CI, 0.27-0.87) and lower HIV knowledge (adjusted odds ratio, 0.96; 95% CI, 0.93
0.99). CONCLUSIONS: Midlife/older methamphetamine-using women with experiences of
partner violence present similar sexual risk profiles, but possess different HIV
related knowledge and attitudes toward prevention methods compared with their
younger counterparts. Clinicians and public health practitioners can have a
positive impact on this overlooked population by assessing HIV risks during
routine screenings, encouraging HIV testing, and providing age-appropriate HIV
prevention education.
PMID- 25128039
TI - Guidelines, training, audit, and quality standards in children's epilepsy
services: closing the loop.
AB - There has been considerable evolution in epilepsy healthcare for children over
the last decade in the United Kingdom. There has been no single explanation for
this. The development of national clinical guidelines, locally delivered but
nationally designed educational programmes, nation-wide clinical audit, clinical
networks and development of designated services have all had complimentary roles
in enabling the implementation of national recommendations for the development of
epilepsy care. These models may be applicable to other healthcare settings
outside the UK.
PMID- 25128040
TI - Review of the Task Force Report on PRO data collection in clinical trials using
mixed modes.
PMID- 25128038
TI - Racial/Ethnic, socioeconomic, and geographic disparities of cervical cancer
advanced-stage diagnosis in Texas.
AB - BACKGROUND: Advanced-stage diagnosis is among the primary causes of mortality
among cervical cancer patients. With the wide use of Pap smear screening,
cervical cancer advanced-stage diagnosis rates have decreased. However,
disparities of advanced-stage diagnosis persist among different population
groups. A challenging task in cervical cancer disparity reduction is to identify
where underserved population groups are. METHODS: Based on cervical cancer
incidence data between 1995 and 2008, this study investigated advanced-stage
cervical cancer disparities in Texas from three social domains: Race/ethnicity,
socioeconomic status (SES), and geographic location. Effects of individual and
contextual factors, including age, tumor grade, race/ethnicity, as well as
contextual SES, spatial access to health care, sociocultural factors, percentage
of African Americans, and insurance expenditures, on these disparities were
examined using multilevel logistic regressions. FINDINGS: Significant variations
by race/ethnicity and SES were found in cervical cancer advanced-stage diagnosis.
We also found a decline in racial/ethnic disparities of advanced cervical cancer
diagnosis rate from 1995 to 2008. However, the progress was slower among African
Americans than Hispanics. Geographic disparities could be explained by age,
race/ethnicity, SES, and the percentage of African Americans in a census tract.
CONCLUSIONS: Our findings have important implications for developing effective
cervical cancer screening and control programs. We identified the location of
underserved populations who need the most assistance with cervical cancer
screening. Cervical cancer intervention programs should target Hispanics and
African Americans, as well as individuals from communities with lower SES in
geographic areas where higher advanced-stage diagnosis rates were identified in
this study.
PMID- 25128041
TI - NICE's selective application of differential discounting: ambiguous,
inconsistent, and unjustified.
AB - The National Institute for Health and Clinical Excellence (NICE) recently
recommended differential discounting of costs and health effects in the economic
appraisal of health care interventions in certain circumstances. The
recommendation was published in an amendment to NICE's Guide to the Methods of
Technology Appraisal. The amendment states that differential discounting should
be applied where "treatment effects are both substantial in restoring health and
sustained over a very long period (normally at least 30 years)." Renewed interest
in differential discounting from NICE is welcome; however, the recommendation's
selective application of differential discounting raises a number of concerns.
The stated criteria for applying differential discounting are ambiguous. The
rationale for the selective application of differential discounting has not been
articulated by NICE and is questionable. The selective application of
differential discounting leads to several inconsistencies, the most concerning of
which is the lower valuation of health gains for those with less than 30 years
remaining life expectancy, which can be interpreted as age discrimination.
Furthermore, the discount rates chosen by NICE do not appear to be informed by
recent advances in the theoretical understanding of differential discounting.
NICE's apparent motivation for recommending differential discounting was to
ensure a favorable cost-effectiveness ratio for a pediatric oncology drug. While
flexibility may be appropriate to allow some interventions that exceed
conventional cost-effectiveness thresholds to be adopted, the selective
adjustment of appraisal methods is problematic and without justification.
PMID- 25128042
TI - The role of economic evaluation in meeting IOM's recommendations on delivering
high-quality cancer care.
PMID- 25128043
TI - PRO data collection in clinical trials using mixed modes: report of the ISPOR PRO
mixed modes good research practices task force.
AB - The objective of this report was to address the use and mixing of data collection
modes within and between trials in which patient-reported outcome (PRO) end
points are intended to be used to support medical product labeling. The report
first addresses the factors that should be considered when selecting a mode or
modes of PRO data collection in a clinical trial, which is often when mixing is
first considered. Next, a summary of how to "faithfully" migrate instruments is
presented followed by a section on qualitative and quantitative study designs
used to evaluate measurement equivalence of the new and original modes of data
collection. Finally, the report discusses a number of issues that must be taken
into account when mixing modes is deemed necessary or unavoidable within or
between trials, including considerations of the risk of mixing at different
levels within a clinical trial program and mixing between different types of
platforms. In the absence of documented evidence of measurement equivalence, it
is strongly recommended that a quantitative equivalence study be conducted before
mixing modes in a trial to ensure that sufficient equivalence can be demonstrated
to have confidence in pooling PRO data collected by the different modes. However,
we also strongly discourage the mixing of paper and electronic field-based
instruments and suggest that mixing of electronic modes be considered for
clinical trials and only after equivalence has been established. If proceeding
with mixing modes, it is important to implement data collection carefully in the
trial itself in a planned manner at the country level or higher and minimize ad
hoc mixing by sites or individual subjects. Finally, when mixing occurs, it must
be addressed in the statistical analysis plan for the trial and the ability to
pool the data must be evaluated to then evaluate treatment effects with mixed
modes data. A successful mixed modes trial requires a "faithful migration,"
measurement equivalence established between modes, and carefully planned
implementation to minimize the risk of increased measurement error impacting the
power of the trial to detect a treatment effect.
PMID- 25128044
TI - An economic evaluation of salt reduction policies to reduce coronary heart
disease in England: a policy modeling study.
AB - OBJECTIVES: Dietary salt intake has been causally linked to high blood pressure
and increased risk of cardiovascular events. Cardiovascular disease causes
approximately 35% of total UK deaths, at an estimated annual cost of L30 billion.
The World Health Organization and the National Institute for Health and Care
Excellence have recommended a reduction in the intake of salt in people's diets.
This study evaluated the cost-effectiveness of four population health policies to
reduce dietary salt intake on an English population to prevent coronary heart
disease (CHD). METHODS: The validated IMPACT CHD model was used to quantify and
compare four policies: 1) Change4Life health promotion campaign, 2) front-of-pack
traffic light labeling to display salt content, 3) Food Standards Agency working
with the food industry to reduce salt (voluntary), and 4) mandatory reformulation
to reduce salt in processed foods. The effectiveness of these policies in
reducing salt intake, and hence blood pressure, was determined by systematic
literature review. The model calculated the reduction in mortality associated
with each policy, quantified as life-years gained over 10 years. Policy costs
were calculated using evidence from published sources. Health care costs for
specific CHD patient groups were estimated. Costs were compared against a "do
nothing" baseline. RESULTS: All policies resulted in a life-year gain over the
baseline. Change4life and labeling each gained approximately 1960 life-years,
voluntary reformulation 14,560 life-years, and mandatory reformulation 19,320
life-years. Each policy appeared cost saving, with mandatory reformulation
offering the largest cost saving, more than L660 million. CONCLUSIONS: All
policies to reduce dietary salt intake could gain life-years and reduce health
care expenditure on coronary heart disease.
PMID- 25128045
TI - Cost-effectiveness models for chronic obstructive pulmonary disease: cross-model
comparison of hypothetical treatment scenarios.
AB - OBJECTIVES: To compare different chronic obstructive pulmonary disease (COPD)
cost-effectiveness models with respect to structure and input parameters and to
cross-validate the models by running the same hypothetical treatment scenarios.
METHODS: COPD modeling groups simulated four hypothetical interventions with
their model and compared the results with a reference scenario of no
intervention. The four interventions modeled assumed 1) 20% reduction in decline
in lung function, 2) 25% reduction in exacerbation frequency, 3) 10% reduction in
all-cause mortality, and 4) all these effects combined. The interventions were
simulated for a 5-year and lifetime horizon with standardization, if possible,
for sex, age, COPD severity, smoking status, exacerbation frequencies, mortality
due to other causes, utilities, costs, and discount rates. Furthermore,
uncertainty around the outcomes of intervention four was compared. RESULTS: Seven
out of nine contacted COPD modeling groups agreed to participate. The 5-year
incremental cost-effectiveness ratios (ICERs) for the most comprehensive
intervention, intervention four, was ?17,000/quality-adjusted life-year (QALY)
for two models, ?25,000 to ?28,000/QALY for three models, and ?47,000/QALY for
the remaining two models. Differences in the ICERs could mainly be explained by
differences in input values for disease progression, exacerbation-related
mortality, and all-cause mortality, with high input values resulting in low ICERs
and vice versa. Lifetime results were mainly affected by the input values for
mortality. The probability of intervention four to be cost-effective at a
willingness-to-pay value of ?50,000/QALY was 90% to 100% for five models and
about 70% and 50% for the other two models, respectively. CONCLUSIONS: Mortality
was the most important factor determining the differences in cost-effectiveness
outcomes between models.
PMID- 25128046
TI - Treating to target with etanercept in rheumatoid arthritis: cost-effectiveness of
dose reductions when remission is achieved.
AB - BACKGROUND: Current management of rheumatoid arthritis (RA) focuses on inducing
remission as early as possible to avoid lasting joint damage, and maintenance of
remission has become important. A 12-month clinical trial in 834 patients with
moderate RA investigated whether etanercept 50 mg/wk could be reduced to half
dose or discontinued in patients who achieved low disease activity after 36
weeks. OBJECTIVE: The objective of this study was to estimate the cost
effectiveness of the three maintenance strategies. METHODS: A Markov model
integrated the three strategies from the clinical trial and extrapolated to 10
years using data from the Swedish RA registry. Assumed treatment strategies after
the trial were similar in all three arms, with patients failing to maintain
remission on half-dose etanercept or methotrexate alone switching to the full
dose of etanercept and patients maintaining remission on full-dose etanercept
allowed switching to half dose. Resource use and utilities were taken from an
observational study. Results are presented as cost/quality-adjusted life-year
(QALY) (both discounted 3%) in the societal perspective. RESULTS: The cost/QALY
gained with half-dose etanercept versus methotrexate ranged from ?14,000 to
?29,000: Longer simulations result in a higher cost/QALY, as the acquisition cost
of etanercept increases. Half-dose etanercept technically dominates the full dose
(lower costs [?-3000 to 6300] and similar effectiveness [0.007-0.011]).
CONCLUSIONS: Although ultimately all three strategies explored achieve a similar
outcome as all three continuously manage patients to maintain remission, it
appears that a dose reduction is the most advantageous strategy in patients with
moderate disease activity.
PMID- 25128047
TI - A framework to evaluate the cost-effectiveness of the NADiA ProsVue slope to
guide adjuvant radiotherapy among men with high-risk characteristics following
prostatectomy for prostate cancer.
AB - OBJECTIVES: The NADiA ProsVue is a prognostic system that measures prostate
specific antigen slope to identify men at lower risk of clinical recurrence of
prostate cancer after radical prostatectomy. We developed a decision-modeling
framework to evaluate its cost-effectiveness to guide the use of adjuvant
radiotherapy (ART). METHODS: We populated the model using patient-level data and
external sources. Patients were classified as intermediate risk or high risk on
the basis of Cancer of the Prostate Risk Assessment-Postsurgical (CAPRA-S)
nomogram and then stratified by the ProsVue slope (<=2 pg/mL/mo; >2 pg/mL/mo) and
receipt of ART. In sensitivity analyses, we varied the effect of the ProsVue
slope on the use of ART and other model parameters. RESULTS: The cost
effectiveness of the ProsVue-guided strategy varied widely because of small
differences in quality-adjusted life-years (QALYs) at 10 years. In the
intermediate-risk group, when the use of ART decreased from 20% (standard care)
to 7.5% among patients with a ProsVue slope value of 2 pg/mL/mo or less, the
incremental cost-effectiveness ratio was $25,160/QALY. In the high-risk group,
the use of ART would have to decrease from 40% (standard care) to 11.5% among
those with a ProsVue slope value of 2 pg/mL/mo or less to obtain a ratio of
$50,000/QALY. The cost-effectiveness ratios were sensitive to varying benefits of
salvage therapy, quality of life, and costs of ART and ProsVue testing.
CONCLUSIONS: The effect of the ProsVue system on costs will be dependent on the
extent to which ART decreases among men identified as having a low risk of
recurrence. Its effect on QALYs will remain conditional on uncertain clinical and
quality-of-life benefits associated with ART.
PMID- 25128048
TI - Time is money, but how much? The monetary value of response time for Thai
ambulance emergency services.
AB - OBJECTIVE: To calculate the monetary value of the time factor per minute and per
year for emergency services. METHODS: The monetary values for ambulance emergency
services were calculated for two different time factors, response time, which is
the time from when a call is received by the emergency medical service call
taking center until the response team arrives at the emergency scene, and
operational time, which includes the time to the hospital. The study was
performed in two steps. First, marginal effects of reduced fatalities and
injuries for a 1-minute change in the time factors were calculated. Second, the
marginal effects and the monetary values were put together to find a value per
minute. RESULTS: The values were found to be 5.5 million Thai bath/min for
fatality and 326,000 baht/min for severe injury. The total monetary value for a 1
minute improvement for each dispatch, summarized over 1 year, was 1.6 billion
Thai baht using response time. CONCLUSIONS: The calculated values could be used
in a cost-benefit analysis of an investment reducing the response time. The
results from similar studies could for example be compared to the cost of moving
an ambulance station or investing in a new alarm system.
PMID- 25128049
TI - A cost-effectiveness analysis of sensor-augmented insulin pump therapy and
automated insulin suspension versus standard pump therapy for hypoglycemic
unaware patients with type 1 diabetes.
AB - OBJECTIVE: To assess the cost-effectiveness of sensor-augmented insulin pump
therapy with "Low Glucose Suspend" (LGS) functionality versus standard pump
therapy with self-monitoring of blood glucose in patients with type 1 diabetes
who have impaired awareness of hypoglycemia. METHODS: A clinical trial-based
economic evaluation was performed in which the net costs and effectiveness of the
two treatment modalities were calculated and expressed as an incremental cost
effectiveness ratio (ICER). The clinical outcome of interest for the evaluation
was the rate of severe hypoglycemia in each arm of the LGS study. Quality-of-life
utility scores were calculated using the three-level EuroQol five-dimensional
questionnaire. Resource use costs were estimated using public sources. RESULTS:
After 6 months, the use of sensor-augmented insulin pump therapy with LGS
significantly reduced the incidence of severe hypoglycemia compared with standard
pump therapy (incident rate difference 1.85 [0.17-3.53]; P = 0.037). Based on a
primary randomized study, the ICER per severe hypoglycemic event avoided was
$18,257 for all patients and $14,944 for those aged 12 years and older. Including
all major medical resource costs (e.g., hospital admissions), the ICERs were
$17,602 and $14,289, respectively. Over the 6-month period, the cost per quality
adjusted life-year gained was $40,803 for patients aged 12 years and older.
CONCLUSIONS: Based on the Australian experience evaluating new interventions
across a broad range of therapeutic areas, sensor-augmented insulin pump therapy
with LGS may be considered a cost-effective alternative to standard pump therapy
with self-monitoring of blood glucose in hypoglycemia unaware patients with type
1 diabetes.
PMID- 25128050
TI - Comparison of contemporaneous EQ-5D and SF-6D responses using scoring algorithms
derived from similar valuation exercises.
AB - OBJECTIVES: Poor agreement between preference-based health-related quality-of
life instruments has been widely reported across patient and community-based
samples. This study compares index scores generated from contemporaneous EQ-5D (3
level version) and SF-6D (SF-36 version) responses using scoring algorithms
derived from independently-conducted Australian population-representative
discrete choice experiments (DCEs), providing the first comparative analysis of
health state valuations using the same method of valuation across the full value
sets. METHODS: EQ-5D and SF-6D responses from seven patient data sets were
transformed into health state valuations using published DCE-derived scoring
algorithms. The empirical comparative evaluation consisted of graphical
illustration of the location and spread of index scores, reporting of basic
descriptive statistics, exploration of between-measure differences in mean index
scores, and analysis of agreement. RESULTS: Compared with previously published
findings regarding the comparability of "conventional" EQ-5D and SF-6D index
scores, health state valuations from the DCE-derived scoring procedures showed
that agreement between scores remained "fair" (intraclass correlation coefficient
values across the seven data sets ranged from 0.375 to 0.615). Mean SF-6D scores
were significantly lower than the respective mean EQ-5D score across all patient
groups (mean difference for the whole sample = 0.253). CONCLUSIONS: The magnitude
of disagreement previously reported between EQ-5D and SF-6D index scores is not
ameliorated through the application of DCE-derived value sets; sizeable
discrepancies remain. These findings suggest that differences between EQ-5D and
SF-6D index scores persist because of their respective descriptive systems.
Further research is required to explore the implications of variations in the
descriptive systems of preference-based instruments.
PMID- 25128051
TI - The effect of presenting information about invasive follow-up testing on
individuals' noninvasive colorectal cancer screening participation decision:
results from a discrete choice experiment.
AB - OBJECTIVES: Many national colorectal cancer screening campaigns have a similar
structure. First, individuals are invited to take a noninvasive screening test,
and, second, in the case of a positive screening test result, they are advised to
undergo a more invasive follow-up test. The objective of this study was to
investigate how much individuals' participation decision in noninvasive screening
is affected by the presence or absence of detailed information about invasive
follow-up testing and how this effect varies over screening tests. METHODS: We
used a labeled discrete choice experiment of three noninvasive colorectal cancer
screening types with two versions that did or did not present respondents with
detailed information about the possible invasive follow-up test (i.e.,
colonoscopy) and its procedure. We used data from 631 Dutch respondents aged 55
to 75 years. Each respondent received only one of the two versions (N = 310 for
the invasive follow-up test information specification version, and N = 321 for
the no-information specification version). RESULTS: Mixed logit model results
show that detailed information about the invasive follow-up test negatively
affects screening participation decisions. This effect can be explained mainly by
a decrease in choice shares for the most preferred screening test (a combined
stool and blood sample test). Choice share simulations based on the discrete
choice experiment indicated that presenting invasive follow-up test information
decreases screening participation by 4.79%. CONCLUSIONS: Detailed information
about the invasive follow-up test has a negative effect on individuals' screening
participation decisions in noninvasive colorectal cancer screening campaigns.
This result poses new challenges for policymakers who aim not only to increase
uptake but also to provide full disclosure to potential screening participants.
PMID- 25128052
TI - Should I stay or should I go home? A latent class analysis of a discrete choice
experiment on hospital-at-home.
AB - OBJECTIVES: This study aimed 1) to quantify the strength of patient preferences
for different aspects of early assisted discharge in The Netherlands for patients
who were admitted with a chronic obstructive pulmonary disease exacerbation and
2) to illustrate the benefits of latent class modeling of discrete choice data.
This technique is rarely used in health economics. METHODS: Respondents made
multiple choices between hospital treatment as usual (7 days) and two
combinations of hospital admission (3 days) followed by treatment at home. The
latter was described by a set of attributes. Hospital treatment was constant
across choice sets. Respondents were patients with chronic obstructive pulmonary
disease in a randomized controlled trial investigating the cost-effectiveness of
early assisted discharge and their informal caregivers. The data were analyzed
using mixed logit, generalized multinomial logit, and latent-class conditional
logit regression. These methods allow for heterogeneous preferences across
groups, but in different ways. RESULTS: Twenty-five percent of the respondents
opted for hospital treatment regardless of the description of the early assisted
discharge program, and 46% never opted for the hospital. The best model contained
four latent classes of respondents, defined by different preferences for the
hospital and caregiver burden. Preferences for other attributes were constant
across classes. Attributes with the strongest effect on choices were the burden
on informal caregivers and co-payments. Except for the number of visits, all
attributes had a significant effect on choices in the expected direction.
CONCLUSIONS: Considerable segments of respondents had fixed preferences for
either treatment option. Applying latent class analysis was essential in
quantifying preferences for attributes of early assisted discharge.
PMID- 25128053
TI - Chinese time trade-off values for EQ-5D health states.
AB - OBJECTIVE: To generate a Chinese general population-based three-level EuroQol
five-dimensios (EQ-5D-3L) social value set using the time trade-off method.
METHODS: The study sample was drawn from five cities in China: Beijing,
Guangzhou, Shenyang, Chengdu, and Nanjing, using a quota sampling method. Utility
values for a subset of 97 health states defined by the EQ-5D-3L descriptive
system were directly elicited from the study sample using a modified Measurement
and Valuation of Health protocol, with each respondent valuing 13 of the health
states. The utility values for all 243 EQ-5D-3L health states were estimated on
the basis of econometric models at both individual and aggregate levels. Various
linear regression models using different model specifications were examined to
determine the best model using predefined model selection criteria. RESULTS: The
N3 model based on ordinary least square regression at the aggregate level yielded
the best model fit, with a mean absolute error of 0.020, 7 and 0 states for which
prediction errors were greater than 0.05 and 0.10, respectively, in absolute
magnitude. This model passed tests for model misspecification (F = 2.7; P =
0.0509, Ramsey Regression Equation Specification Error Test), heteroskedasticity
(chi(2) = 0.97; P = 0.3254, Breusch-Pagan/Cook-Weisberg test), and normality of
the residuals (chi(2) = 1.285; P = 0.5259, Jarque-Bera test). The range of the
predicted values (-0.149 to 0.887) was similar to those estimated in other
countries. CONCLUSIONS: The study successfully developed Chinese utility values
for EQ-5D-3L health states using the time trade-off method. It is the first
attempt ever to develop a standardized instrument for quantifying quality
adjusted life-years in China.
PMID- 25128054
TI - The effects of total knee arthroplasty on physical functioning and health among
the under age 65 population.
AB - OBJECTIVES: This study examined the effects of total knee arthroplasty on six
measures of physical functioning, self-rated health, pain, earnings, and
employment status among US adults aged 51 to 63 years at baseline. METHODS: Data
came from the Health and Retirement Study, a nationally representative
longitudinal study conducted biannually. The analysis sample consisted of
individuals aged 51 to 63 years at baseline with arthritis who were resurveyed at
2-year intervals from 1996 to 2010. Propensity score matching was used to compare
outcomes of persons receiving total knee arthroplasty (TKA) with those of matched
controls. Six measures of physical functioning were examined: lower-body mobility
problems, instrumental activities of daily living limitations, activities of
daily living limitations, and large muscle, fine motor, and gross motor
limitations. Self-rated health and pain were also examined. The two employment
related outcomes were earnings and employment status. RESULTS: Receipt of TKA was
associated with better outcomes for several measures of physical functioning,
especially mobility limitations, pain, and self-rated health. Receipt of TKA was
not associated with increased earnings or employment. CONCLUSIONS: Receipt of TKA
yields important improvements in physical function among persons with an
arthritis diagnosis who received the procedure before reaching the age of 65
years. This study contributes to knowledge about the benefits of TKA in a
community setting among nonelderly recipients of TKA.
PMID- 25128056
TI - Two approaches to incorporate clinical data uncertainty into multiple criteria
decision analysis for benefit-risk assessment of medicinal products.
AB - BACKGROUND: The Problem formulation, Objectives, Alternatives, Consequences,
Trade-offs, Uncertainties, Risk attitude, and Linked decisions (PrOACT-URL)
framework and multiple criteria decision analysis (MCDA) have been recommended by
the European Medicines Agency for structured benefit-risk assessment of medicinal
products undergoing regulatory review. OBJECTIVE: The objective of this article
was to provide solutions to incorporate the uncertainty from clinical data into
the MCDA model when evaluating the overall benefit-risk profiles among different
treatment options. METHODS: Two statistical approaches, the delta-method approach
and the Monte-Carlo approach, were proposed to construct the confidence interval
of the overall benefit-risk score from the MCDA model as well as other
probabilistic measures for comparing the benefit-risk profiles between treatment
options. Both approaches can incorporate the correlation structure between
clinical parameters (criteria) in the MCDA model and are straightforward to
implement. RESULTS: The two proposed approaches were applied to a case study to
evaluate the benefit-risk profile of an add-on therapy for rheumatoid arthritis
(drug X) relative to placebo. It demonstrated a straightforward way to quantify
the impact of the uncertainty from clinical data to the benefit-risk assessment
and enabled statistical inference on evaluating the overall benefit-risk profiles
among different treatment options. CONCLUSIONS: The delta-method approach
provides a closed form to quantify the variability of the overall benefit-risk
score in the MCDA model, whereas the Monte-Carlo approach is more computationally
intensive but can yield its true sampling distribution for statistical inference.
The obtained confidence intervals and other probabilistic measures from the two
approaches enhance the benefit-risk decision making of medicinal products.
PMID- 25128057
TI - An updated method for risk adjustment in outcomes research.
AB - OBJECTIVE: To demonstrate why meta-analytic methods need modification before they
can be used to aggregate rates or effect sizes in outcomes research, under the
constraint of no common underlying effect or rate. METHODS: Studies are presented
that require different types of risk adjustment. First, we demonstrate using
rates that external risk adjustment through standardization can be achieved using
modified meta-analytic methods, but only with a model that allows input of user
defined weights. Next, we extend these observations to internal risk adjustment
of comparative effect sizes. RESULTS: We show that this procedure produces
identical results to conventional age standardization if a rate is being
standardized for age. We also demonstrate that risk adjustment of effect sizes
can be achieved with this modified method but cannot be done using standard meta
analysis. CONCLUSIONS: We conclude that this method allows risk adjustment to be
performed in situations in which currently the fixed- or random-effects methods
of meta-analysis are inappropriately used. The latter should be avoided when the
underlying aim is risk adjustment rather than meta-analysis.
PMID- 25128055
TI - Physician social networks and variation in rates of complications after radical
prostatectomy.
AB - OBJECTIVES: Variation in care within and across geographic areas remains poorly
understood. The goal of this article was to examine whether physician social
networks-as defined by shared patients-are associated with rates of complications
after radical prostatectomy. METHODS: In five cities, we constructed networks of
physicians on the basis of their shared patients in 2004-2005 Surveillance,
Epidemiology and End Results-Medicare data. From these networks, we identified
subgroups of urologists who most frequently shared patients with one another.
Among men with localized prostate cancer who underwent radical prostatectomy, we
used multilevel analysis with generalized linear mixed-effect models to examine
whether physician network structure-along with specific characteristics of the
network subgroups-was associated with rates of 30-day and late urinary
complications, and long-term incontinence after accounting for patient-level
sociodemographic, clinical factors, and urologist patient volume. RESULTS:
Networks included 2677 men in five cities who underwent radical prostatectomy.
The unadjusted rate of 30-day surgical complications varied across network
subgroups from an 18.8 percentage-point difference in the rate of complications
across network subgroups in city 1 to a 26.9 percentage-point difference in city
5. Large differences in unadjusted rates of late urinary complications and long
term incontinence across subgroups were similarly found. Network subgroup
characteristics-average urologist centrality and patient racial composition-were
significantly associated with rates of surgical complications. CONCLUSIONS:
Analysis of physician networks using Surveillance, Epidemiology and End Results
Medicare data provides insight into observed variation in rates of complications
for localized prostate cancer. If validated, such approaches may be used to
target future quality improvement interventions.
PMID- 25128058
TI - Improving the contribution of regulatory assessment reports to health technology
assessments--a collaboration between the European Medicines Agency and the
European network for Health Technology Assessment.
AB - In response to a recommendation from the Pharmaceutical Forum, the European
Medicines Agency and the European network for Health Technology Assessment
initiated a collaboration with the aim to improve the contribution regulatory
assessment reports can make to the assessment of relative effectiveness of
medicinal products by health technology assessment bodies. This collaboration on
improving European Public Assessment Reports (EPARs) started in February 2010 and
was performed over 2 years. As a result, the templates for preparing EPARs were
revised to better address the needs of heath technology organizations. The better
understanding of information needs was a key outcome of the collaboration. To
ascertain whether these template changes led to the inclusion of relevant
information, a review of a small set of EPARs for recently approved medicinal
products was carried out in parallel by both the European network for Health
Technology Assessment and the European Medicines Agency. This report provides an
account of this project on improving EPARs, which is part of the ongoing dialogue
between regulators and health technology assessment bodies on a European level to
support policymaker decisions in the future.
PMID- 25128059
TI - A comparison of national guidelines for network meta-analysis.
AB - OBJECTIVES: Within technology appraisals, it is necessary to compare the complete
set of treatments that may be used in the patient group under consideration.
Randomized controlled trials are a key source of evidence for these comparisons.
The techniques of network meta-analysis allow the networks of trial evidence to
be evaluated to obtain estimates of comparative efficacy between sets of
treatments. These techniques may be the only source of estimates of comparative
effectiveness if trials directly comparing the treatments of interest have not
been conducted, and may provide useful additional evidence if both direct and
indirect comparisons exist. METHODS: We examined both published and draft
guidelines from reimbursement and health technology appraisal bodies, and
considered their recommendations using appropriate methodology for the conduct of
indirect comparisons and the assessments of their validity. RESULTS: Guidelines
from 33 countries were reviewed. Of these, guidelines from 9 countries-Australia,
Belgium, Canada, France, Germany, Scotland, Spain, South Africa, and the United
Kingdom (England and Wales)-included detailed recommendations on the conduct of
network meta-analysis. The recommendations were summarized. CONCLUSIONS: No two
recommendations from the multiple national guidelines are mutually exclusive. It
is possible to perform one network meta-analysis for submission to multiple
national jurisdictions.
PMID- 25128060
TI - Cognitive overload? An exploration of the potential impact of cognitive
functioning in discrete choice experiments with older people in health care.
AB - OBJECTIVES: This exploratory study sought to investigate the effect of cognitive
functioning on the consistency of individual responses to a discrete choice
experiment (DCE) study conducted exclusively with older people. METHODS: A DCE to
investigate preferences for multidisciplinary rehabilitation was administered to
a consenting sample of older patients (aged 65 years and older) after surgery to
repair a fractured hip (N = 84). Conditional logit, mixed logit, heteroscedastic
conditional logit, and generalized multinomial logit regression models were used
to analyze the DCE data and to explore the relationship between the level of
cognitive functioning (specifically the absence or presence of mild cognitive
impairment as assessed by the Mini-Mental State Examination) and preference and
scale heterogeneity. RESULTS: Both the heteroscedastic conditional logit and
generalized multinomial logit models indicated that the presence of mild
cognitive impairment did not have a significant effect on the consistency of
responses to the DCE. CONCLUSIONS: This study provides important preliminary
evidence relating to the effect of mild cognitive impairment on DCE responses for
older people. It is important that further research be conducted in larger
samples and more diverse populations to further substantiate the findings from
this exploratory study and to assess the practicality and validity of the DCE
approach with populations of older people.
PMID- 25128061
TI - LEF1 regulates glioblastoma cell proliferation, migration, invasion, and cancer
stem-like cell self-renewal.
AB - Glioblastoma multiforme (GBM; WHO grade IV) is one of the most common primary
tumors of the central nervous system. This disease remains one of the incurable
human malignancies because the molecular mechanism driving the GBM development
and recurrence is still largely unknown. Here, we show that knockdown of
lymphocyte enhancer factor-1 (LEF1), a major transcription factor of Wnt pathway,
inhibits U251 cell migration, invasion, and proliferation. Furthermore,
downregulation of LEF1 expression inhibits the self-renewal capacity of U251 GBM
stem-like cells and decreases the expression level of the GBM stem-like cell
(GSC) markers such as CD133 and nestin. Our findings reveal that LEF1 maintains
the GBM cell proliferation, migration, and GBM stem-like cell self-renewal. Taken
together, these results suggest that LEF1 may be a novel therapeutic target for
GBM suppression.
PMID- 25128062
TI - Over-expression of TRPM8 is associated with poor prognosis in urothelial
carcinoma of bladder.
AB - Transient receptor protein (TRP) channels are frequently associated with tumors
and are correlated to patient's outcome. We firstly investigated TRP channel
melastatin 8 (TRPM8) expression in urothelial carcinoma of bladder (UCB) and its
correlation with UCB clinicopathological features and additionally evaluated the
association between TRPM8 expression and patients' survival rate to elucidate its
role in bladder oncogenesis. Real-time quantitative reverse transcription
polymerase chain reaction (qRT-PCR) was conducted to examine TRPM8 messenger RNA
(mRNA) expression in 36 pairs of freshly frozen UCB tissues and matched
noncancerous tissues. Immunohistochemistry (IHC) was performed in 156 archived
paraffin-embedded UCB samples to explore the correlation between TRPM8 protein
and clinicopathological features. The association between TRPM8 expression and
patient's survival rate was evaluated using the Kaplan-Meier method and
multivariate Cox regression analysis, respectively. The expression levels of
TRPM8 mRNA in UCB tissues were significantly higher than those in matched
noncancerous tissues (P=0.016). Expression of TRPM8 protein in UCB was
significantly and positively associated with histological grade (P=0.039) and
tumor stage (P=0.037). Significant correlation between high TRPM8 expression and
poor cumulative survival of UCB patients was shown using the Kaplan-Meier
survival curve (P=0.039). TRPM8 was represented as an independent prognostic
biomarker for UCB patients by multivariate Cox regression analysis (P=0.047). The
present study provide the convincing evidence for the first time that over
expression of TRPM8 may play a role in the pathogenesis and progression of UCB,
and TRPM8 may serve as an independent prognostic biomarker for UCB patients.
PMID- 25128063
TI - Lin28 promotes Her2 expression and Lin28/Her2 predicts poorer survival in gastric
cancer.
AB - The main purpose of this study is to investigate the interactions between Lin28
and Her2 in gastric cancer. Lin28 and Her2 expression were evaluated in
surgically resected samples of 298 gastric cancer patients using
immunohistochemical staining. The correlations between Lin28/Her2 expression and
clinical variables were retrospectively analyzed. The mRNA level of LIN28 and
HER2 was detected by reverse-transcriptase polymerase chain reaction. Among all
gastric cancer patients, 33.9% (101/298) were determined as Her2-positive, and
43.0% (128/298) were defined as Lin28-positive. Lin28 was significantly
associated with Her2, advanced tumor stage, lesion size, and Ki67 level (p<0.05
for each). Kaplan-Meier analysis illustrated that both Lin28 and Her2 are poor
prognostic factors in gastric cancer; Lin28(+)/Her2(+) patients have the poorest
survival (median survival = 17 months, p<0.01). Multivariate Cox analysis showed
that Lin28 is a significant prognostic factor (hazard ratio (HR) = 1.79, 95%
confidence interval (CI) 1.23-2.62). Further stratification analysis indicated
that Lin28 may be a prognostic factor in chemotherapy. In vitro data on MKN-28
and MKN-45 cells showed that Lin28 can upregulate Her2 expression at
translational level. Both Lin28 and Her2 are poor prognostic factors in gastric
cancer. Lin28 may regulate Her2 post-transcriptionally in gastric cancer cells,
which indicates it might be a potential target in the treatment of gastric
cancer.
PMID- 25128064
TI - Designing a recombinant chimeric construct contain MUC1 and HER2 extracellular
domain for prediagnostic breast cancer.
AB - Breast cancer is the most common cancer among women in the world. One of the
approaches for diagnosis of breast cancer is detection of its tumor-associated
markers. Mucin 1 (MUC1), a tumor-associated antigen, is a transmembrane
glycoprotein expressed by normal epithelial cells and overexpressed by carcinomas
of epithelial origin. Also, human epidermal growth factor receptor-2 (HER2/erbB
2) belongs to the one of four members of tyrosin kinase type 1 family in which
overexpression of HER2 is associated with malignancy in breast cancer. This study
was aimed to bioinformatics analysis and designing a recombinant chimeric protein
containing MUC1 and HER2 antigens to express in prokaryotic host (Escherichia
coli) as breast cancer diagnosis tools. The immunogenic sequences of MUC1 and
HER2 were extracted and fused together by a linker. The chimeric construct was
analyzed by bioinformatics softwares. The optimization and purification,
evaluation of the expression of chimeric protein was performed using Western
blotting, ELISA, and immunohistochemistry. The results showed that the chimeric
construct was stable and immunogenic domains were exposed. The pET-28a vector
containing chimeric gene had high level of protein expression. The recombinant
chimeric protein was confirmed using Western blotting, and it was investigated
using ELISA and IHC. Then, the MUC1 and HER2 combined peptides can be used as
coating antigens in ELISA for detection of antibodies against MUC1 or HER2 in
human serum.
PMID- 25128065
TI - Apoptotic effect of genistein on human colon cancer cells via inhibiting the
nuclear factor-kappa B (NF-kappaB) pathway.
AB - Genistein possesses a wide variety of biological activities, and it is best known
for its ability to inhibit cancer progression. Its cancer-preventive effect has
been attributed to various mechanisms, including the induction of cell cycle
arrest and apoptosis as well as the antioxidant functions. Nuclear factor kappa-B
(NF-kappaB) is a signaling pathway that controls transcriptional activation of
genes important for the tight regulation of many cellular processes and is
aberrantly expressed in many types of cancer. Inhibitors of NF-kappaB pathway
have shown potential anti-tumor activities. However, it is not fully elucidated
in colon cancer. In the present study, we demonstrated that genistein could
induce apoptosis in human colon cancer LoVo and HT-29 cells through inhibiting NF
kappaB pathway, as well as downregulation of Bcl-2 and upregulation of Bax, thus
providing basis for clinical application of genistein in colon cancer cases.
PMID- 25128068
TI - A randomized controlled clinical trial of formalin for treatment of chronic
hemorrhagic radiation proctopathy in cervical carcinoma patients.
AB - PURPOSE: Chronic hemorrhagic radiation proctopathy is not uncommon after
radiotherapy for cervical carcinoma. The outcomes of several treatments have been
variable. Many studies demonstrate that topical treatment with 4 % formalin is
effective and safe. However, a nonrandomized control study showed a high response
rate and good tolerance in chronic radiation proctopathy patients treated with 10
% formalin. The optimal concentration of formalin therefore remains unclear.
METHODS: To compare the effectiveness and safety of 4 and 10 % formalin for the
treatment of chronic hemorrhagic radiation proctopathy, a prospective trial was
conducted at the Department of Gynecology of the Affiliated Hospital of Binzhou
Medical College from January 2009 to December 2012. One hundred and twenty
patients with chronic hemorrhagic radiation proctopathy following radiotherapy
for cervical carcinoma were recruited and randomized to receive 4 or 10 %
formalin. A standard protocol was followed for formalin application. Symptom and
rectoscopy scores were evaluated before and at 12 weeks after treatment. RESULTS:
In the 4 % formalin group, 49 (86.0 %) and 53 (91.4 %) patients showed an
improvement in symptom score and rectoscopy score, respectively (P = 0.36).
Symptom and rectoscopy scores decreased significantly after treatment in both the
4 % formalin group and the 10 % formalin group (P < 0.001). Symptom score was
correlated with rectoscopy score (P < 0.001). More patients in the 10 % group
suffered treatment-related complications than did those in the 4 % group (P =
0.03). CONCLUSIONS: For the treatment of chronic hemorrhagic radiation
proctopathy, 4 % should be the preferred formalin concentration.
PMID- 25128067
TI - Musculoskeletal pain and health-related quality of life among breast cancer
patients treated with aromatase inhibitors.
AB - OBJECTIVE: This study aims to examine the associations between musculoskeletal
pain and health-related quality of life (HR-QOL) among breast cancer patients on
aromatase inhibitors (AIs) and women without a history of breast cancer. METHODS:
A cross-sectional study was conducted among 68 breast cancer patients on AIs for
an average of 3.5 years and 137 postmenopausal women without a history of cancer.
Musculoskeletal pain was assessed using a 10-cm visual analog scale; HR-QOL was
examined using the Medical Outcomes Study Short Form (SF-36) health survey.
Linear regression was used to estimate the associations between pain and HR-QOL
in both groups. RESULTS: Approximately 64 % of the breast cancer patients and
women in the comparison group reported musculoskeletal pain. Among women with
breast cancer, those with pain had significantly lower HR-QOL scores in the
physical (52.2 vs. 42.6; p < 0.001) and mental (52.7 vs. 45.5; p = 0.01)
component summary scores compared with those without pain. In the comparison
group, pain was associated with significantly lower scores in the physical (55.4
vs. 46.0; p < 0.001), but not the mental, component summary score (52.1 vs. 52.4;
p = 0.82). The significant associations between pain and HR-QOL persisted after
confounder adjustment in both groups. Among women with similar severity of pain,
breast cancer patients reported significantly lower HR-QOL in the mental summary
component compared with the women in the comparison group. CONCLUSIONS: Among
breast cancer patients, musculoskeletal pain adversely affects both mental and
physical components of HR-QOL. Preventing or treating AI-associated
musculoskeletal pain may improve overall HR-QOL among breast cancer patients
treated with AIs.
PMID- 25128070
TI - Mesenchymal stem cells in lung cancer tumor microenvironment: their biological
properties, influence on tumor growth and therapeutic implications.
AB - The tumor microenvironment (TME) of lung cancer has been documented to play an
important role in participating in tumor disease progression. As the precursor of
most stroma in TME, mesenchymal stem cells (MSCs) draw great attention since
evidence has suggested that MSCs derived from lung cancer patients present a
different phenotype compared to their normal counterparts. Furthermore, MSCs
could be recruited towards tumor sites and influence tumor survival, although the
effect remains contradictory. Our review will summarize the current advance of
the role MSCs in lung cancer and explore the possible treatment strategies by
blocking their crosstalk.
PMID- 25128069
TI - Transcription factor OCT4 promotes cell cycle progression by regulating CCND1
expression in esophageal carcinoma.
AB - The CCND1 gene is overexpressed in esophageal cancer and accelerates cell cycle
progression. However, the mechanism whereby the upstream genes or factors
directly regulate CCND1 expression remains unknown. By analyzing the 5'-UTR
region of the CCND1 gene, we found that this region contains an octamer motif
(ATTTTGCAT), which suggests that the expression of CCND1 might be directly
associated with octamer-binding transcription factor 4 (OCT4). In this study, the
wild-type and the octamer motif-mutanted CCND1 promoters were cloned, and their
corresponding luciferase reporter vectors were then constructed to study the
molecular mechanism by which OCT4 regulates the expression of CCND1 and
influences the biological behaviors of esophageal cancer cells. The results
indicated that suppressing the expression of CCND1 and OCT4 in esophageal cancer
cells reduced cell proliferative and invasive abilities, induced cell cycle G1
phase arrest, and slowed the growth of xenografts in nude mice. Suppression of
OCT4 expression significantly decreased the wild-type CCND1 promoter activity and
down-regulated the expression of CCND1, but did not affect the activity of the
mutant promoter. Whereas, suppression of CCND1 did not affect OCT4 expression,
suggesting that OCT4 regulates CCND1 expression by activating the CCND1 promoter
and subsequently promoting cell cycle progression. The results revealed and
confirmed that OCT4 is the upstream factor that directly binds to the CCND1
promoter to regulate CCND1 expression, then to promote cell cycle progression and
accelerate the proliferation and invasion of esophageal cancer cells. This
finding may significantly contribute to elucidating the regulatory mechanism
involved in the cell cycle progression of esophageal cancer cells and may aid in
screening potential gene targets for the biological therapy of esophageal cancer.
PMID- 25128071
TI - The p38 MAPK-regulated PKD1/CREB/Bcl-2 pathway contributes to selenite-induced
colorectal cancer cell apoptosis in vitro and in vivo.
AB - Supranutritional selenite has anti-cancer therapeutic effects in vivo; however,
the detailed mechanisms underlying these effects are not clearly understood.
Further studies would broaden our understanding of the anti-cancer effects of
this compound and provide a theoretical basis for its clinical application. In
this study, we primarily found that selenite exposure inhibited phosphorylation
of cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB),
leading to suppression of Bcl-2 in HCT116 and SW480 colorectal cancer (CRC)
cells. Moreover, the selenite-induced inhibitory effect on PKD1 activation was
involved in suppression of the CREB signalling pathway. Additionally, we
discovered that selenite treatment can upregulate p38 MAPK phosphorylation, which
results in inhibition of the PKD1/CREB/Bcl-2 survival pathway and triggers
apoptosis. Finally, we established a colorectal cancer xenograft model and found
that selenite treatment markedly inhibits tumour growth through the
MAPK/PKD1/CREB/Bcl-2 pathway in vivo. Our results demonstrated that a
supranutritional dose of selenite induced CRC cell apoptosis through inhibition
of the PKD1/CREB/Bcl-2 axis both in vitro and in vivo.
PMID- 25128072
TI - Increased cardiovascular disease mortality associated with excessive exercise in
heart attack survivors.
AB - OBJECTIVE: To test whether greater exercise is associated with progressively
lower mortality after a cardiac event. PATIENTS AND METHODS: We used Cox
proportional hazard analyses to examine mortality vs estimated energy expended by
running or walking measured as metabolic equivalents (3.5 mL O2/kg per min per
day or metabolic equivalent of task-h/d [MET-h/d]) in 2377 self-identified heart
attack survivors, where 1 MET-h/d is the energy equivalent of running 1 km/d.
Mortality surveillance via the National Death Index included January 1991 through
December 2008. RESULTS: A total of 526 deaths occurred during an average
prospective follow-up of 10.4 years, 376 (71.5%) of which were related to
cardiovascular disease (CVD) (International Statistical Classification of
Diseases, 10th Revision codes I00-I99). CVD-related mortality compared with the
lowest exercise group decreased by 21% for 1.07 to 1.8 MET-h/d of running or
walking (P=.11), 24% for 1.8 to 3.6 MET-h/d (P=.04), 50% for 3.6 to 5.4 MET-h/d
(P=.001), and 63% for 5.4 to 7.2 MET-h/d (P<.001) but decreased only 12% for
>=7.2 MET-h/d (P=.68). These data represent a 15% average risk reduction per MET
h/d for CVD-related mortality through 7.2 MET-h/d (P<.001) and a 2.6-fold risk
increase above 7.2 MET-h/d (P=.009). Relative to the risk reduction at 7.2 MET
h/d, the risk for >=7.2 MET-h/d increased 3.2-fold (P=.006) for all ischemic
heart disease (IHD)-related mortalities but was not significantly increased for
non-IHD-CVD, arrhythmia-related CVD, or non-CVD-related mortalities. CONCLUSION:
Running or walking decreases CVD mortality risk progressively at most levels of
exercise in patients after a cardiac event, but the benefit of exercise on CVD
mortality and IHD deaths is attenuated at the highest levels of exercise
(running: above 7.1 km/d or walking briskly: 10.7 km/d).
PMID- 25128073
TI - Exercising for health and longevity vs peak performance: different regimens for
different goals.
PMID- 25128074
TI - Elite athletes live longer than the general population: a meta-analysis.
AB - OBJECTIVE: To perform a meta-analysis of cohort studies aimed at providing an
accurate overview of mortality in elite athletes. PATIENTS AND METHODS: We
reviewed English-language scientific articles available in Medline and Web of
Science databases following the recommendations of the Meta-analyses Of
Observational Studies in Epidemiology group. We searched for publications on
longevity and professional or elite athletes (with no restriction on the starting
date and up to March 31, 2014). RESULTS: Ten studies, including data from a total
of 42,807 athletes (707 women), met all inclusion criteria. The all-cause pooled
standard mortality ratio (SMR) was 0.67 (95% CI, 0.55-0.81; P<.001) with no
evidence of publication bias (P=.24) but with significant heterogeneity among
studies (I(2)=96%; Q=224.46; P<.001). Six studies provided data on cardiovascular
disease (CVD) and 5 on cancer (in a total of 35,920 and 12,119 athletes,
respectively). When only CVD was considered as a cause of mortality, the pooled
SMR was 0.73 (95% CI, 0.65-0.82; P<.001) with no evidence of bias (P=.68) or
heterogenity among studies (I(2)=38%; Q=8.07; P=.15). The SMR for cancer was 0.60
(95% CI, 0.38-0.94; P=.03) with no evidence of bias (P=.20) despite a significant
heterogeneity (I(2)=91%; Q=44.21; P<.001). CONCLUSION: The evidence available
indicates that top-level athletes live longer than the general population and
have a lower risk of 2 major causes of mortality, namely, CVD and cancer.
PMID- 25128075
TI - Strategy to address innovative off-label medication use in China: grading
management.
PMID- 25128076
TI - Effects of "Fit fOR The Aged" (FORTA) on pharmacotherapy and clinical endpoints-
a pilot randomized controlled study.
AB - PURPOSE: The feasibility of applying the Fit fOR The Aged (FORTA) list, a drug
classification combining positive and negative labeling of drugs, should be
studied in geriatric patients and medication quality and clinical endpoints
measured. FORTA labels range from A (indispensable), B (beneficial), C
(questionable) to D (avoid). METHODS: A prospective randomized controlled pilot
trial was performed in hospitalized geriatric patients in whom the FORTA
instrument or standard care was applied. Patients were randomly admitted to an
intervention and a control ward. Changes of FORTA label distributions between
admission and discharge, over- and under-prescription rates, clinical endpoints
including the number of falls during the hospitalization, and Barthel Index (BI)
at admission and discharge were measured. RESULTS: Polypharmacy persisted in both
groups. At discharge, a higher rate of A drugs was prescribed in the intervention
group (58 patients, median age 84 years) vs. standard care (56 patients, median
age 83 years, p < 0.02), and both over- and under-prescriptions were
significantly lower in the FORTA than in the control group (p < 0.03). Two (3.4%)
intervention, but 12 (21.4%) control, patients fell at least once (p < 0.001).
The fall rate per 1,000 patient years was 1.5 +/- 8.3 in the intervention and
10.6 +/- 25.4 in the control group (p < 0.004). CONCLUSIONS: This pilot study
shows that the application of the FORTA list is feasible in geriatric patients.
In this small study, the medication quality improved in the intervention group,
but polypharmacy persisted in both groups. The fall rate was significantly lower
in the intervention group. These encouraging results must be interpreted
carefully.
PMID- 25128077
TI - Coexistence of neurofibroma and meningioma at exactly the same level of the
cervical spine.
AB - We report a case of the coexistence of different spinal tumors at the same level
of the cervical spine, without neurofibromatosis (NF), which was successfully
treated with surgery. A 72-year-old female presented with right upper-limb
clumsiness and weakness. Magnetic resonance imaging revealed an intradural,
extramedullary tumor mass at the right C3-4 level with extradural extension into
the intervertebral foramen. The extradural tumor was removed, and the pathology
showed neurofibroma. After incision of the dura, the intradural tumor was
removed, and was identified as meningioma in the pathological report. The patient
did not meet the criteria of NF. Coexistence of neurofibroma and meningioma at
exactly the same level of the spine without NF is extremely rare. Exploration of
the intradural space may be necessary after resection of an extradural tumor if
the surgical finding does not correlate well with the preoperative images.
PMID- 25128078
TI - Stents in paediatric and adult congenital interventional cardiac catheterization.
AB - A 'stent' is a tubular meshed endoprosthesis that has contributed to the
development of interventional catheterization over the past 30 years. In
congenital heart diseases, stents have offered new solutions to the treatment of
congenital vessel stenosis or postsurgical lesions, to maintain or close shunt
patency, and to allow transcatheter valve replacement. First, stents were made of
bare metal. Then, stent frameworks evolved to achieve a better compromise between
radial strength and flexibility. However, almost all stents used currently in
children have not been approved for vascular lesions in children and are
therefore used 'off-label'. Furthermore, the inability of stents to follow
natural vessel growth still limits their use in low-weight children and infants.
Recently, bioresorbable stents have been manufactured and may overcome this
issue; they are made from materials that may dissolve or be absorbed in the body.
In this review, we aim to describe the history of stent development, the
technical characteristics of stents used currently, the clinical applications and
results, and the latest technological developments and perspectives in paediatric
and adult congenital cardiac catheterization.
PMID- 25128079
TI - First report on intraoperative vector flow imaging of the heart among patients
with healthy and diseased aortic valves.
AB - The vector velocity method Transverse Oscillation (TO) implemented on a
conventional ultrasound (US) scanner (ProFocus, BK Medical, Herlev, Denmark) can
provide real-time, angle-independent estimates of the cardiac blood flow. During
cardiac surgery, epicardial US examination using TO was performed on (A) 3
patients with healthy aortic valve and (B) 3 patients with aortic valve stenosis.
In group B, the systolic flow of the ascending aorta had higher velocities, was
more aliased and chaotic. The jet narrowed to 44% of the lumen compared to 75% in
group A and with a vector concentration, a measure of flow complexity, of 0.41
compared to 0.87 in group A. The two groups had similar secondary flow of the
ascending aorta with an average rotation frequency of 4.8 Hz. Simultaneous
measurements were obtained with spectral Doppler (SD) and a thermodilution
technique (TD). The mean difference in peak systolic velocity compared to SD in
group A was 22% and 45% in B, while the mean difference in volume flow compared
to TD in group A was 30% and 32% in B. TO can potentially reveal new information
of cardiac blood flow, and may become a valuable diagnostic tool in the
evaluation of patients with cardiovascular diseases.
PMID- 25128080
TI - Dentin-smear remains at self-etch adhesive interface.
AB - OBJECTIVE: The bonding potential of 'mild' self-etch adhesives may be compromised
due to smear interference, as they may not dissolve/penetrate the smear layer
effectively due to their relatively low acidity. We observed that the thickness
of the dentin smear layer differed depending on the surface-preparation
methodology used. METHODS: The interaction of an (ultra-)mild self-etch adhesive
(Clearfil S3 Bond, Kuraray Noritake) with human dentin, prepared either using a
medium-grit diamond bur ('thick', clinically relevant smear layer) or 600-grit
SiC-paper ('thin' smear layer), or just fractured (smear-free), was evaluated
using high-resolution transmission electron microscopy (TEM). Non
demineralized/demineralized 30-100nm interfacial cross-sections were prepared
following common TEM-specimen processing and diamond-knife ultra-microtomy.
RESULTS: The adhesive did not dissolve the bur-cut, nor the SiC-ground smear
layer, but impregnated it. Within this 'resin-smear complex', hydroxyapatite was
abundantly present. At fractured dentin, this complex was not present, while the
actual layer of interaction of the adhesive was limited to about 100nm. Non
demineralized 'ultra-thin' (30-50nm) sections confirmed the interfacial ultra
structure to differ for the three surface-preparation methods. An electron dense
band was consistently disclosed at the adhesive interface, most likely
representing the documented chemical interaction of the functional monomer 10-MDP
with Ca. SIGNIFICANCE: The dentin surface-preparation method significantly
affects the nature of the smear layer and the interaction with the ultra-mild
self-etch adhesive.
PMID- 25128081
TI - Detection of the Helicobacter pylori dupA gene is strongly affected by the PCR
design.
AB - The Helicobacter pylori virulence gene dupA is usually detected by PCR, but the
primer binding sites used are highly variable. Our newly designed qPCR against a
conserved region of dupA was positive in 64.2% of 394 clinical isolates while the
positivity rate of the commonly used PCRs ranged from 29.9% to 37.8%.
PMID- 25128082
TI - A tagged parathyroid hormone derivative as a carrier of antibody cargoes
transported by the G protein coupled PTH1 receptor.
AB - Based on the known fact that the parathyroid hormone (PTH) might be extended at
its C-terminus with biotechnological protein cargoes, a vector directing the
secretion of PTH1-84 C-terminally fused with the antigenic epitope myc (PTH-myc)
was exploited. The functional properties and potential of this analog for imaging
PTH1R-expressing cells were examined. The PTH-myc construct was recombinantly
produced as a conditioned medium (CM) of transfected HEK 293a cells (typical
concentrations of 187nM estimated with ELISAs for PTH). PTH-myc CM induced cyclic
AMP formations (10min), with a minor loss of potency relative to authentic PTH1
84, and c-Fos expression (1-3h). Treatment of recipient HEK 293a cells
transiently expressing PTH1R with PTH-myc CM (supplemented with a fluorescent
monoclonal anti-myc tag antibody, either 4A6 or 9E10) allowed the labeling of
endosomal structures positive for Rab5 and/or for beta-arrestin1 (microscopy,
cytofluorometry). Authentic PTH was inactive in this respect, ruling out a non
specific form of endocytosis like pinocytosis. Using a horseradish peroxidase
conjugated secondary antibody, the endocytosis of the PTH-myc-based antibody
complex by endogenous PTH1R was evidenced in MG-63 osteoblastoid cells. The
secreted construct PTH-myc represents a bona fide agonist that supports the
feasibility of transporting cargoes of considerable molecular weight inside cells
using arrestin and Rab5-mediated PTH1R endocytosis. PTH-myc is also transported
into cells that express PTH1R at a physiological level. Such tagged peptide
hormones may be part of a cancer chemotherapy scheme exploiting a modular
cytotoxic secondary antibody and the receptor repertoire expressed in a given
tumor.
PMID- 25128083
TI - DEK oncogene expression during normal hematopoiesis and in Acute Myeloid Leukemia
(AML).
AB - DEK is important in regulating cellular processes including proliferation,
differentiation and maintenance of stem cell phenotype. The translocation t(6;9)
in Acute Myeloid Leukemia (AML), which fuses DEK with NUP214, confers a poor
prognosis and a higher risk of relapse. The over-expression of DEK in AML has
been reported, but different studies have shown diminished levels in pediatric
and promyelocytic leukemias. This study has characterized DEK expression, in
silico, using a large multi-center cohort of leukemic and normal control cases.
Overall, DEK was under-expressed in AML compared to normal bone marrow (NBM).
Studying specific subtypes of AML confirmed either no significant change or a
significant reduction in DEK expression compared to NBM. Importantly, the
similarity of DEK expression between AML and NBM was confirmed using
immunohistochemistry analysis of tissue mircorarrays. In addition, stratification
of AML patients based on median DEK expression levels indicated that DEK showed
no effect on the overall survival of patients. DEK expression during normal
hematopoiesis did reveal a relationship with specific cell types implicating a
distinct function during myeloid differentiation. Whilst DEK may play a potential
role in hematopoiesis, it remains to be established whether it is important for
leukemagenesis, except when involved in the t(6;9) translocation.
PMID- 25128085
TI - Nonlinear behaviour of conduction and block in cardiac tissue with heterogeneous
expression of connexin 43.
AB - Altered gap junctional coupling potentiates slow conduction and arrhythmias. To
better understand how heterogeneous connexin expression affects conduction at the
cellular scale, we investigated conduction in tissue consisting of two
cardiomyocyte populations expressing different connexin levels. Conduction was
mapped using microelectrode arrays in cultured strands of foetal murine
ventricular myocytes with predefined contents of connexin 43 knockout (Cx43KO)
cells. Corresponding computer simulations were run in randomly generated two
dimensional tissues mimicking the cellular architecture of the strands. In the
cultures, the relationship between conduction velocity (CV) and Cx43KO cell
content was nonlinear. CV first decreased significantly when Cx43KO content was
increased from 0 to 50%. When the Cx43KO content was >=60%, CV became comparable
to that in 100% Cx43KO strands. Co-culturing Cx43KO and wild-type cells also
resulted in significantly more heterogeneous conduction patterns and in frequent
conduction blocks. The simulations replicated this behaviour of conduction. For
Cx43KO contents of 10-50%, conduction was slowed due to wavefront meandering
between Cx43KO cells. For Cx43KO contents >=60%, clusters of remaining wild-type
cells acted as electrical loads that impaired conduction. For Cx43KO contents of
40-60%, conduction exhibited fractal characteristics, was prone to block, and was
more sensitive to changes in ion currents compared to homogeneous tissue. In
conclusion, conduction velocity and stability behave in a nonlinear manner when
cardiomyocytes expressing different connexin amounts are combined. This behaviour
results from heterogeneous current-to-load relationships at the cellular level.
Such behaviour is likely to be arrhythmogenic in various clinical contexts in
which gap junctional coupling is heterogeneous.
PMID- 25128084
TI - A comparative study on the risks of radiogenic second cancers and cardiac
mortality in a set of pediatric medulloblastoma patients treated with photon or
proton craniospinal irradiation.
AB - PURPOSE: To compare the risks of radiogenic second cancers and cardiac mortality
in 17 pediatric medulloblastoma patients treated with passively scattered proton
or field-in-field photon craniospinal irradiation (CSI). MATERIAL/METHODS:
Standard of care photon or proton CSI treatment plans were created for all 17
patients in a commercial treatment planning system (TPS) (Eclipse version 8.9;
Varian Medical Systems, Palo Alto, CA) and prescription dose was 23.4 or 23.4 Gy
(RBE) to the age specific target volume at 1.8 Gy/fraction. The therapeutic doses
from proton and photon CSI plans were estimated from TPS. Stray radiation doses
were determined from Monte Carlo simulations for proton CSI and from measurements
and TPS for photon CSI. The Biological Effects of Ionization Radiation VII report
and a linear model based on childhood cancer survivor data were used for risk
predictions of second cancer and cardiac mortality, respectively. RESULTS: The
ratios of lifetime attributable risk (RLARs) (proton/photon) ranged from 0.10 to
0.22 for second cancer incidence and ranged from 0.20 to 0.53 for second cancer
mortality, respectively. The ratio of relative risk (RRR) (proton/photon) of
cardiac mortality ranged from 0.12 to 0.24. The RLARs of both cancer incidence
and mortality decreased with patient's age at exposure (e), while the RRRs of
cardiac mortality increased with e. Girls had a significantly higher RLAR of
cancer mortality than boys. CONCLUSION: Passively scattered proton CSI provides
superior predicted outcomes by conferring lower predicted risks of second cancer
and cardiac mortality than field-in-field photon CSI for all medulloblastoma
patients in a large clinically representative sample in the United States, but
the magnitude of superiority depends strongly on the patients' anatomical
development status.
PMID- 25128086
TI - Caveolin-1 deletion exacerbates cardiac interstitial fibrosis by promoting M2
macrophage activation in mice after myocardial infarction.
AB - Adverse remodeling following myocardial infarction (MI) leading to heart failure
is driven by an imbalanced resolution of inflammation. The macrophage cell is an
important control of post-MI inflammation, as macrophage subtypes secrete
mediators to either promote inflammation and extend injury (M1 phenotype) or
suppress inflammation and promote scar formation (M2 phenotype). We have
previously shown that the absence of caveolin-1 (Cav1), a membrane scaffolding
protein, is associated with adverse cardiac remodeling in mice, but the
mechanisms responsible remain to be elucidated. We explore here the role of Cav1
in the activation of macrophages using wild type C57BL6/J (WT) and Cav1(tm1Mls/J)
(Cav1(-/-)) mice. By echocardiography, cardiac function was comparable between WT
and Cav1(-/-) mice at 3days post-MI. In the absence of Cav1, there were a
surprisingly higher percentage of M2 macrophages (arginase-1 positive) detected
in the infarcted zone. Conversely, restoring Cav1 function after MI in WT mice by
adding back the Cav1 scaffolding domain reduced the M2 activation profile.
Further, adoptive transfer of Cav1 null macrophages into WT mice on d3 post-MI
exacerbated adverse cardiac remodeling at d14 post-MI. In vitro studies revealed
that Cav1 null macrophages had a more pronounced M2 profile activation in
response to IL-4 stimulation. In conclusion, Cav1 deletion promotes an array of
maladaptive repair processes after MI, including increased TGF-beta signaling,
increased M2 macrophage infiltration and dysregulation of the M1/M2 balance. Our
data also suggest that cardiac remodeling can be improved by therapeutic
intervention regulating Cav1 function during the inflammatory response phase.
PMID- 25128087
TI - SENP5, a SUMO isopeptidase, induces apoptosis and cardiomyopathy.
AB - Cardiomyopathy presents a major health issue and is a leading cause of heart
failure. Although a subset of familial cardiomyopathy is associated with genetic
mutations, over 50% of cardiomyopathy is defined as idiopathic, the mechanisms
underlying which are under intensive investigation. SUMO conjugation is a dynamic
posttranslational modification that can be readily reversed by the activity of
sentrin-specific proteases (SENPs). However, whether SENPs are implicated in
heart disease pathophysiology remains unexplored. We observed a significant
increase in the level of SENP5, a SUMO isopeptidase, in human idiopathic failing
hearts. To reveal whether it plays a role in the pathogenesis of cardiac muscle
disorders, we used a gain-of-function approach to overexpress SENP5 in murine
cardiomyocytes (SENP5 transgenic, SENP5-Tg). Overexpression of SENP5 led to
cardiac dysfunction, accompanied by decreased cardiomyocyte proliferation and
elevated apoptosis. The increase in apoptosis preceded other detectable
pathological changes, suggesting its causal link to cardiomyopathy. Further
examination of SENP5-Tg hearts unveiled a decrease in SUMO attachment to dynamin
related protein (Drp1), a factor critical for mitochondrial fission.
Correspondingly, the mitochondria of SENP5-Tg hearts at an early developmental
stage were significantly larger compared with those in the control hearts,
suggesting that desumoylation of Drp1 at least partially accounts for the cardiac
phenotypes observed in the SENP5-Tg mice. Finally, overexpression of Bcl2 in
SENP5-Tg hearts improved cardiac function of SENP5-Tg mice, further supporting
the notion that SENP5 mainly targets mitochondrial function in vivo. Our findings
demonstrate an important role of the desumoylation enzyme SENP5 in the
development of cardiac muscle disorders, and point to the SUMO conjugation
pathway as a potential target in the prevention/treatment of cardiomyopathy. This
article is part of a Special Issue entitled "Mitochondria: From Basic
Mitochondrial Biology to Cardiovascular Disease".
PMID- 25128088
TI - Effects of chronic administration of arachidonic acid on lipid profiles and
morphology in the skeletal muscles of aged rats.
AB - Arachidonic acid (20:4n-6, ARA) is a major component of the cell membrane,
whereas ARA-derived eicosanoids are formed when cells are damaged. Aging is
associated with an accretion of oxidative stress in skeletal muscles. In this
study, we examined the effects of chronic administration (13 weeks) of ARA (240
mg/kg/day) on fatty acid composition, antioxidative status, and morphology of
slow (soleus muscles) and fast (extensor digitorum longus muscles; EDL)-twitch
muscles in aged rats (21 months old). The level of reactive oxygen species was
higher in the EDL of ARA-administered rats than in that of control rats. ARA
administration decreased the muscle cell volumes and increased the number of slow
myosin heavy chain (MHC)-positive cells in the EDL. The relative content of MHC2X
was increased whereas the relative content of MHC2B was decreased in the EDL of
ARA-administered rats. These results suggest that ARA deposition in the fast
twitch muscle of aged rats reduced cell volume with an increase in oxidative
stress.
PMID- 25128089
TI - Central venous occlusion mimics carotid cavernous fistula: a case report and
review of the literature.
AB - A patient presented with signs and symptoms of a left carotid cavernous fistula
(CCF). Computed tomography angiography confirmed filling of the cavernous sinus
in the arterial phase. Cerebral digital subtraction angiography demonstrated no
evidence of CCF. The workup, diagnosis, and treatment of this patient are
discussed, and the literature is reviewed.
PMID- 25128090
TI - Cosmetic fat augmentation following breast reconstruction: sonographic appearance
with cytopathologic correlation.
AB - This series presents the history and imaging of patients who had cosmetic fat
augmentation following mastectomy and reconstruction. The cases provide the
useful reminder that a complete surgical history is essential when assessing the
imaging of a post-operative breast patient and that speaking directly with
patients can be a critical step in putting together a complete clinical picture
and adding value to their care.
PMID- 25128091
TI - Cellular immune response in patients with chronic hepatitis B virus infection.
AB - Hepatitis, cirrhosis and hepatocellular carcinoma caused by hepatitis B virus
(HBV) infection has threatening human health seriously. As HBV is a kind of non
cytotoxic virus, host immune response plays a vital role in pathogenesis and
clinical outcomes of hepatitis B. Multiple immune cells (e.g., including
cytotoxic T lymphocytes, regulatory T cells, natural killer cells, dendritic
cells) are important in the immune regulation of HBV infection. Therefore,
focusing on the activation states of immune cells may provide new evidences and
strategies for determining immune status of HBV infectors, monitoring progression
of diseases and predicting efficacy of antiviral treatment.
PMID- 25128092
TI - Apoptotic activity and Treg cells in tissue lesions of patients with leprosy.
AB - In order to understand the apoptotic response and the participation of Treg cells
in the spectral clinical evolution of leprosy, this study evaluated the
immunohistochemical expression of caspase-3 and FoxP3 in skin lesions of leprosy
patients with the polar forms of the disease. Forty-nine patients with a
confirmed diagnosis of the disease were selected, including 27 with the TT form
and 22 with the LL form. Quantitative analysis of caspase-3 immunostaining showed
a higher expression of this mediator in the LL form (3.409 +/- 0.6517
cells/mm(2); p = 0.0001). Immunostaining for the transcription factor FoxP3 was
higher in the LL form (3.891 +/- 0.9294 cells/mm(2); p = 0.0001). A moderate
correlation between the two markers was observed in the TT form (r = 0.5214; p =
0.005). It can be concluded that Treg cells and apoptosis play an effective role
for the host defense response, inducing mechanisms involved in the activation of
cascades that interfere with the control of the immune response and cell
homeostasis.
PMID- 25128093
TI - Dynamic computed tomography angiography in suspected brain death: a noninvasive
biomarker.
AB - PURPOSE: Neurologic determination of death or brain death is primarily a clinical
diagnosis. This must respect all guarantees required by law and should be
determined early to avoid unnecessary treatment and allow organ harvesting for
transplantation. Ancillary testing is used in situations in which clinical
assessment is impossible or confounded by other factors. Our purpose is to
determine the utility of dynamic computed tomographic angiography (dCTA) as an
ancillary test for diagnosis of brain death. MATERIALS AND METHODS: We
retrospectively reviewed 13 consecutive patients with suspected brain death in
the intensive care unit who had dCTA. Contrast appearance timings recorded from
the dCTA data were compared to findings from 15 controls selected from patients
who presented with symptoms of acute stroke but showed no stroke in follow-up
imaging. RESULTS: The dCTA allows us to reliably assess cerebral blood flow and
to record time of individual cerebral vessels opacification. It also helps us to
assess the intracranial flow qualitatively against the flow in extracranial
vessels as a reference. We compared the time difference between enhancement of
the external and internal carotid arteries and branches. In all patients who were
brain dead, internal carotid artery enhancement was delayed, which occurred after
external carotid artery branches were opacified. CONCLUSION: In patients with
suspected brain death, dCTA reliably demonstrated the lack of cerebral blood
flow, with extracranial circulation as an internal reference. Our initial results
suggest that inversion of time of contrast appearance between internal carotid
artery and external carotid artery branches at the skull base could predict a
lack of distal intracranial flow.
PMID- 25128094
TI - Looking back, moving forward: an analysis of complaints submitted to a Canadian
tertiary care radiology department and lessons learned.
AB - PURPOSE: We present an analysis of various types and strata of complaints
received in a geographically isolated tertiary care center over a 2.5-year
period. METHODS: Research ethics board approval was obtained. The institution
described is a closed system with formalized procedures for submitting
complaints. All complaints submitted between November 2010 and March 2013 were
collected retrospectively. The following data were extracted: type of
complainant, nature of the complaint, site or modality of concern, dates in
question, and the response. The data were analysed in multiple subgroups and
compared with patient and study volume data. RESULTS: The frequency of complaints
equalled 0.01% (100/1,050,000). The largest group of those who submitted
complaints were patients (69% [69/100]), followed by referring physicians (16%).
Examination scheduling and interpersonal conflicts were equally of greatest
frequency of concern (21% [21/100]), followed by issues with study reporting
(16%). The average time interval between complaint submission and formal address
was 15 days. CONCLUSIONS: We present a low frequency of complaints, with the
majority of these complaints submitted by patients; scheduling and personal
interactions were most often involved. Effective communication, both with
patients and referring physicians, was identified as a particular focus for
improving satisfaction.
PMID- 25128095
TI - The crosslinking of polysaccharides with polyamines and dextran-polyallylamine
antibacterial hydrogels.
AB - A facile modular approach to rapidly prepare pH-responsive hydrogels by
crosslinking polysaccharides with polyamines is demonstrated. Hydrogels are
prepared by first reacting the less reactive polysaccharides with the cross
linker epichlorohydrin and completed by the addition of polyamines. The
crosslinking of polysaccharides with polyamines provides a facile method for
incorporating functionality into polysaccharide based hydrogels. This process is
demonstrated with the polysaccharides dextran, pullulan and carboxymethyl
cellulose and with the polyamines polyallylamine and polyethylene imine. The
hydrogels were characterized by FTIR and swelling studies, which showed pH
dependent swelling due to the presence of the polyamine. The hydrogels can also
be tailored by varying the mass ratio between the polysaccharide and polyamine.
Absorption studies of organic analytes showed the polyamine content affecting the
uptake of a charged substrate (methylene blue) and no effect on a neutral
substrate (6-methyl coumarin). This synthetic method was also used to prepare
hydrogels with antibacterial activity against E. coli and S. aureus by utilizing
an amphiphilic polyallylamine.
PMID- 25128096
TI - Free-radical scavenging properties and antioxidant activities of botryosphaeran
and some other beta-D-glucans.
AB - beta-D-Glucans are known to present antitumor, anticancer, and anti-inflammatory
activities that are influenced by their own antioxidant capacity. The antioxidant
activity of botryosphaeran, an exopolysaccharide of the (1 -> 3;1 -> 6)-beta-D
glucan type produced by the Botryosphaeria rhodina MAMB-05 was evaluated and
compared to some other beta-D-glucans (lasiodiplodan an exocellular (1 -> 6)-beta
D-glucan from Lasiodiplodia theobromae, laminarin and curdlan), and
oligosaccharides, disaccharides, and monosaccharides in a study of scavenging
activities of free radicals in-vitro. Botryosphaeran displayed high total
antioxidant activity (80%) as well as good scavenging activity against hydroxyl
radical (90.6%), superoxide anion (37%), hydrogen peroxide (38%), and nitric
oxide radical (90%). No reducing power, metal-chelating capacity or inhibition of
lipid peroxidation was observed for these beta-D-glucans. The results
demonstrated that botryosphaeran exhibited effective antioxidant activity as
supported by many different assays, suggesting that this beta-D-glucan may serve
as a source of a new bioactive compound with effective antioxidant activity.
PMID- 25128097
TI - Production of alpha-amylase for the biosynthesis of gold nanoparticles using
Streptomyces sp. MBRC-82.
AB - Marine actinobacterial synthesis of gold nanoparticles has good potential to
develop simple, cost-effective and eco-friendly methods for production of
important biomaterials. In this context, gold nanoparticles have attracted
considerable attention in recent years, owing to their various applications. In
this paper, we report on the production of alpha-amylase for the extracellular
synthesis of gold nanoparticles using Streptomyces sp. MBRC-82. Medium
composition and culture conditions for alpha-amylase production were
statistically optimized. Plackett-Burman design was employed to find out the
optimal medium constituents and culture conditions to enhance alpha-amylase
production. Box-Behnken design revealed that three independent variables namely
soluble starch (5.8484 g), peptone (3.5191 g), and NaCl (0.3829) significantly
influenced alpha-amylase production. The gold nanoparticles were characterized by
ultraviolet-visible (UV-vis) spectrometer, X-ray diffractometer (XRD), Fourier
transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM),
energy dispersive X-ray analysis (EDXA), and transmission electron microscopy
(TEM). The particles synthesized using the optimized enzyme activity ranged from
20 to 80 nm with an average particle size of 40 nm and therefore can be extended
to various medicinal applications.
PMID- 25128098
TI - New heterocycle modified chitosan adsorbent for metal ions (II) removal from
aqueous systems.
AB - A new hydrogel based on a modified chitosan CS-B was synthesized and evaluated
for its metal ion removal from aqueous systems. The CS-B hydrogel was prepared
through modification of chitosan with 4-((1, 3-dioxoisoindolin-2-ylimino) methyl)
benzaldehyde as a heterocyclic component. The new hydrogel was analyzed by
diverse techniques such as FTIR, XRD, TGA, SEM, and swelling tests. The
adsorption capacity of CS-B for metal ions Co(2+), Hg(2+), Cu(2+), Zn(2+), and
Pb(2+) from aqueous systems at different pH values showed various levels of
efficiency. The metal ion uptake data over a range of pH values for Co(2+) and
Hg(2+) showed the highest adsorption capacity while Cu(2+), Zn(2+), and Pb(2+)
showed moderate adsorption capacity. Selective metal ion efficiency was highest
for Co(2+) and lowest for Hg(2+) in their binary mixture.
PMID- 25128099
TI - Identification, characterization, immobilization of a novel type hydrolase (LmH)
from Listeria monocytogenes.
AB - A novel type of hydrolase (LmH) from Listeria monocytogenes was identified,
characterized, and immobilized for biotechnological applications. Primary
sequence analysis indicated that LmH had a catalytic triad (Ser(91)-Asp(192)
His(222)) with a molecular weight of 27.8 kDa. Homologs of this enzyme are
produced by many Gram-positive bacteria including Bacillus, Staphylococcus, and
Enterococcus. Biochemical properties of LmH were investigated by performing mass
spectrometry, dynamic light scattering (DLS), enzyme assays, enantioselective
analysis, circular dichroism (CD) spectroscopy, fluorescence analysis, and
macroscopic hydrogel formations. Interestingly, cross-linked enzyme aggregates
(CLEAs) of LmH exhibited enhanced stability and good recycling abilities compared
to free LmH. These molecular characteristics of LmH highlight its great potential
for the pharmaceutical, biotechnological, and chemical industries.
PMID- 25128100
TI - Comments on: "Quantitative evaluation of mechanical properties in tissue
engineered auricular cartilage".
PMID- 25128101
TI - A woman with warts, leg swelling, and deafness.
AB - KEY TEACHING POINTS * We describe a 45-year-old woman with GATA2 deficiency
associated with verrucae, lymphedema, immunodeficiency, and a history of
infections and skin cancer. * GATA2 deficiency has variable clinical expressivity
with differing presentations, including infection, hematopoietic abnormalities,
immunodeficiency, lymphedema, and cancer. * Cutaneous manifestations include
verruca vulgaris, soft tissue infections, lymphedema, and panniculitis. *
Patients may have verrucae that can progress to squamous cell carcinomas;
dermatologists therefore play an important role in managing these patients as
members of a multidisciplinary team.
PMID- 25128102
TI - Topical antimicrobial acne treatment tolerability: a meaningful factor in
treatment adherence?
PMID- 25128103
TI - The impact of obesity on the folliculosebaceous unit.
PMID- 25128104
TI - Reply to 'what is the effect of obesity on the folliculosebaceous unit?'.
PMID- 25128105
TI - Skin cancer, photoprotection, and skin of color.
PMID- 25128106
TI - Reply to 'skin cancer, photoprotection, and skin of color'.
PMID- 25128107
TI - Surgical margins for possibly malignant melanocytic lesions.
PMID- 25128108
TI - Psoriasis or obesity is a risk factor for nonalcoholic fatty liver disease.
PMID- 25128109
TI - Reply to 'surgical margins for possibly malignant melanocytic lesions'.
PMID- 25128110
TI - Reply: surgical margins for possibly malignant melanocytic lesions and the
overdiagnosis of melanoma.
PMID- 25128111
TI - Complementary data for long-term infliximab use in psoriasis.
PMID- 25128112
TI - Reply to 'complementary data for long-term infliximab use in psoriasis'.
PMID- 25128113
TI - Filaggrin mutations as an archetype for understanding the pathophysiology of
atopic dermatitis.
PMID- 25128114
TI - Frontal fibrosing alopecia.
PMID- 25128115
TI - Reply to 'frontal fibrosing alopecia'.
PMID- 25128116
TI - Clinical efficacy of diphenylcyclopropenone in alopecia areata: retrospective
data analysis of 50 patients.
PMID- 25128117
TI - Early-onset mycosis fungoides among African American women: a single-institution
study.
PMID- 25128118
TI - Evaluation and diagnosis of the hair loss patient: part I. History and clinical
examination.
AB - Hair loss (alopecia) is a common problem and is often a major source of distress
for patients. The differential diagnosis of alopecia includes both scarring and
nonscarring alopecias. In addition, many hair shaft disorders can produce hair
shaft fragility, resulting in different patterns of alopecia. Therefore, an
organized and systematic approach is needed to accurately address patients'
complaints to achieve the correct diagnosis. Part 1 of this 2-part continuing
medical education article on alopecia describes history taking and the clinical
examination of different hair loss disorders. It also provides an algorithmic
diagnostic approach based on the most recent knowledge about different types of
alopecia.
PMID- 25128119
TI - Evaluation and diagnosis of the hair loss patient: part II. Trichoscopic and
laboratory evaluations.
AB - The use of trichoscopy for evaluating a number of hair and scalp disorders is
gaining popularity. It is a simple and noninvasive in vivo tool for visualizing
hair shafts and the scalp. Recently, alopecias have been classified according to
their trichoscopic findings. The second part of this 2-part continuing medical
education article reviews recent advances in this field and describes a
systematic approach for using the differential diagnostic findings of trichoscopy
in alopecia.
PMID- 25128120
TI - Papular eruption associated with palifermin.
PMID- 25128121
TI - A 52-year-old man with bullous pemphigoid and bullous cystitis.
PMID- 25128122
TI - Successful topical adapalene treatment for the facial lesions of an adolescent
case of epidermolytic ichthyosis.
PMID- 25128125
TI - Trichoblastoma with dermoscopic features of a malignant tumor: three cases.
PMID- 25128126
TI - Periungual Bowen disease mimicking chronic paronychia and diagnosed by
dermoscopy.
PMID- 25128127
TI - Optimizing the efficacy of targeted phototherapy by marking early vitiligo
lesions after visualizing under a Wood's lamp.
PMID- 25128128
TI - Use of the Unna sleeve for severe, treatment-resistant idiopathic pruritus.
PMID- 25128129
TI - Extraosseous extension of multiple myeloma: a cutaneous herald to systemic
disease.
PMID- 25128130
TI - Solar urticaria to visible light triggered by light-emitting diode therapy.
PMID- 25128131
TI - Cheilitis and urticaria associated with stannous fluoride in toothpaste.
PMID- 25128132
TI - Distinctive cutaneous findings due to a rare complication from a warming device.
PMID- 25128133
TI - Reactive hemophagocytic syndrome in a patient with adult-onset Still disease.
PMID- 25128134
TI - Umbilical endometriosis elucidates cause of recurrent pneumothorax.
PMID- 25128135
TI - Generalized granuloma annulare after varicella infection: Wolf isotopic response?
PMID- 25128136
TI - Photo-induced Stevens-Johnson syndrome.
PMID- 25128137
TI - Pili multigemini/trichofolliculoma-like organoid nevus.
PMID- 25128138
TI - Subcorneal pustular dermatosis associated with Mycoplasma pneumoniae infection.
PMID- 25128139
TI - Rapid deterioration in a patient with primary aggressive cutaneous epidermotropic
CD8+ cytotoxic T-cell ('Berti') lymphoma after administration of adalimumab.
PMID- 25128140
TI - Rickettsia parkeri: eschar diagnosis.
PMID- 25128141
TI - A rapidly progressive and fatal case of atypical acute generalized exanthematous
pustulosis.
PMID- 25128142
TI - Peripheral facial palsy after topical photodynamic therapy for facial actinic
keratoses.
PMID- 25128143
TI - Demodicidosis on the arms of a patient with pemphigus foliaceus.
PMID- 25128144
TI - Primary cutaneous nocardiosis in an immunocompetent host following laser
resurfacing.
PMID- 25128145
TI - Giant cellulitis-like Sweet syndrome in the setting of autoimmune disease.
PMID- 25128146
TI - Cutaneous polyarteritis nodosa presenting as a solitary blue toe.
PMID- 25128147
TI - Major response to vemurafenib in patient with severe cutaneous Langerhans cell
histiocytosis harboring BRAF V600E mutation.
PMID- 25128148
TI - Extensive scleredema adultorum with loss of eccrine glands.
PMID- 25128149
TI - Downregulation of microRNA-498 in colorectal cancers and its cellular effects.
AB - miR-498 is a non-coding RNA located intergenically in 19q13.41. Due to its
predicted targeting of several genes involved in control of cellular growth, we
examined the expression of miR-498 in colon cancer cell lines and a large cohort
of patients with colorectal adenocarcinoma. Two colon cancer cancer cell lines
(SW480 and SW48) and one normal colonic epithelial cell line (FHC) were
recruited. The expression of miR-498 was tested in these cell lines by using
quantitative real-time polymerase chain reaction (qRT-PCR). Tissues from 80
patients with surgical resection of colorectum (60 adenocarcinomas and 20 non
neoplastic tissues) were tested for miR-498 expression by qRT-PCR. In addition,
an exogenous miR-498 (mimic) was used to detect the miRNA's effects on cell
proliferation and cell cycle events in SW480 using MTT calorimetric assay and
flow cytometry respectively. The colon cancer cell lines showed reduced
expression of miR-498 compared to a normal colonic epithelial cell line. Mimic
driven over expression of miR-498 in the SW480 cell line resulted in reduced cell
proliferation and increased proportions of G2-M phase cells. In tissues, miR-498
expression was too low to be detected in all colorectal adenocarcinoma compared
to non-neoplastic tissues. This suggests that the down regulation of miR-498 in
colorectal cancer tissues and the direct suppressive cellular effect noted in
cancer cell lines implies that miR-498 has some direct or indirect role in the
pathogenesis of colorectal adenocarcinomas.
PMID- 25128151
TI - Effect of cholesterol and ergosterol on the antibiotic amphotericin B
interactions with dipalmitoylphosphatidylcholine monolayers: X-ray reflectivity
study.
AB - Amphotericin B is a Streptomyces nodosus metabolite and one of the oldest polyene
antibiotics used in the treatment of invasive systemic fungal infections. Despite
its over 50-year existence in clinical practice and the recognition of
amphotericin B as the gold standard in the treatment of serious systemic mycosis,
it still remains one of the most toxic pharmaceuticals. Understanding of the
processes at the molecular levels and the interactions between amphotericin B
with lipid membranes containing sterols should elucidate the mechanisms of the
action and toxicity of this widely used antibiotic. In this work, we use X-ray
reflectivity to study the structural changes on a molecular scale after
amphotericin B incorporation. These changes are accompanied by an increase in
monolayer surface pressure which is more pronounced for ergosterol - rather than
cholesterol-rich membranes. The data indicate that this difference is not due to
the higher affinity of amphotericin B towards ergosterol-containing membranes but
is rather due to a ~3Angstrom corrugation of the monolayer. Furthermore, the
total quantity of amphotericin B incorporated into lipid monolayers containing
cholesterol and ergosterol is the same.
PMID- 25128152
TI - Characterization of 3-methoxy flavones for their interaction with ABCG2 as
suggested by ATPase activity.
AB - Breast Cancer Resistance Protein (BCRP/ABCG2) belongs to the superfamily of ATP
binding cassette (ABC) transporters. Characteristic of some of these transporter
proteins is the transport of a variety of structurally unrelated substances
against a concentration gradient by using the energy of ATP hydrolysis. ABCG2 has
been found to confer multidrug resistance (MDR) in cancer cells. Several
anticancer drugs have been identified as ABCG2 substrates including mitoxantrone,
etoposide and topotecan. As inhibition of the transporter is one of the
strategies to overcome MDR, we have synthesized and tested several 3-methoxy
flavones and investigated them for their ABCG2 inhibition. Among these,
pentamethyl quercetin (compound 4) and pentamethyl morin (compound 5) were found
to be fluorescent and hence screened for their possible transport by ABCG2 using
confocal microscopy. This study showed that pentamethyl quercetin was far less
accumulated in ABCG2 overexpressing MDCK BCRP cells as compared to MDCK sensitive
cells, suggesting possible efflux of this compound by ABCG2. Pentamethyl morin
showed no visible difference in both cell lines. Based on this observation, we
studied several other fluorescent 3-methoxy flavones for their accumulation in
ABCG2 overexpressing cells. To confirm the substrate or inhibitor nature of the
tested compounds, these compounds were further investigated by ATPase assay. If
stimulation of the transporter ATPase activity is detected, one can conclude that
the compound is probably a transported substrate. All compounds except
pentamethyl morin (compound 5) and tetramethyl quercetin (compound 6) were found
to stimulate ATPase activity pointing to possible substrates despite being potent
inhibitors of ABCG2.
PMID- 25128153
TI - Labeling phospholipid membranes with lipid mimetic luminescent metal complexes.
AB - Lipid-mimetic metallosurfactant based luminophores are promising candidates for
labeling phospholipid membranes without altering their biophysical
characteristics. The metallosurfactants studied exhibit high structural and
physicochemical similarity to phospholipid molecules, designed to incorporate
into the membrane structure without the need for covalent attachment to a lipid
molecule. In this work, two lipid-mimetic phosphorescent metal complexes are
described: [Ru(bpy)2(dn-bpy)](2+) and [Ir(ppy)2(dn-bpy)](+) where bpy is 2,2'
bipyridine, dn-bpy is 4,4'-dinonyl-2,2'-bipyridine and ppy is 2-phenylpyridine.
Apart from being lipid-mimetic in size, shape and physical properties, both
complexes exhibit intense photoluminescence and enhanced photostability compared
with conventional organic fluorophores, allowing for prolonged observation.
Moreover, the large Stokes shift and long luminescence lifetime associated with
these complexes make them more suitable for spectroscopic studies. The complexes
are easily incorporated into dimyristoil-phosphatidyl-choline (DMPC) liposomes by
mixing in the organic solvent phase. DLS reveals the labeled membranes form
liposomes of similar size to that of neat DMPC membrane. Synchrotron Small-Angle
X-ray Scattering (SAXS) measurements confirmed that up to 5% of either complex
could be incorporated into DMPC membranes without producing any structural
changes in the membrane. Fluorescence microscopy reveals that 0.5% label content
is sufficient for imaging. Atomic Force Microscopic imaging confirms that
liposomes of the labeled bilayers on a mica surface can fuse into a flat lamellar
membrane that is morphologically identical to neat lipid membranes. These results
demonstrate the potential of such lipid-mimetic luminescent metal complexes as a
new class of labels for imaging lipid membranes.
PMID- 25128150
TI - A syndecan-4 binding peptide derived from laminin 5 uses a novel PKCepsilon
pathway to induce cross-linked actin network (CLAN) formation in human trabecular
meshwork (HTM) cells.
AB - In this study, we examined the role(s) of syndecan-4 in regulating the formation
of an actin geodesic dome structure called a cross-linked actin network (CLAN) in
which syndecan-4 has previously been localized. CLANs have been described in
several different cell types, but they have been most widely studied in human
trabecular meshwork (HTM) cells where they may play a key role in controlling
intraocular pressure by regulating aqueous humor outflow from the eye. In this
study we show that a loss of cell surface synedcan-4 significantly reduces CLAN
formation in HTM cells. Analysis of HTM cultures treated with or without
dexamethasone shows that laminin 5 deposition within the extracellular matrix is
increased by glucocorticoid treatment and that a laminin 5-derived, syndecan-4
binding peptide (PEP75), induces CLAN formation in TM cells. This PEP75-induced
CLAN formation was inhibited by heparin and the broad spectrum PKC inhibitor Ro
31-7549. In contrast, the more specific PKCalpha inhibitor Go 6976 had no effect,
thus excluding PKCalpha as a downstream effector of syndecan-4 signaling.
Analysis of PKC isozyme expression showed that HTM cells also expressed both
PKCgamma and PKCepsilon. Cells treated with a PKCepsilon agonist formed CLANs
while a PKCalpha/gamma agonist had no effect. These data suggest that syndecan-4
is essential for CLAN formation in HTM cells and that a novel PKCepsilon-mediated
signaling pathway can regulate formation of this unique actin structure.
PMID- 25128154
TI - Structural dynamics of the cell wall precursor lipid II in the presence and
absence of the lantibiotic nisin.
AB - Representing a physiological "Achilles' heel", the cell wall precursor lipid II
(LII) is a prime target for various classes of antibiotics. Over the years LII
binding agents have been recognized as promising candidates and templates in the
search for new antibacterial compounds to complement or replace existing drugs.
To elucidate the molecular structural basis underlying LII functional mechanism
and to better understand if and how lantibiotic binding alters the molecular
behavior of LII, we performed molecular dynamics (MD) simulations of phospholipid
membrane-embedded LII in the absence and presence of the LII-binding lantibiotic
nisin. In a series of 2*4 independent, unbiased 100ns MD simulations we sampled
the conformational dynamics of nine LII as well as nine LII-nisin complexes
embedded in an aqueous 150mM NaCl/POPC phospholipid membrane environment. We
found that nisin binding to LII induces a reduction of LII mobility and
flexibility, an outward shift of the LII pentapeptide, an inward movement of the
LII disaccharide section, and an overall deeper insertion of the LII tail group
into the membrane. The latter effect might indicate an initial step in adopting a
stabilizing, scaffold-like structure in the process of nisin-induced membrane
leakage. At the same time nisin conformation and LII interaction remain similar
to the 1WCO LII-nisin NMR solution structure.
PMID- 25128155
TI - Towards the importance of minimum toe clearance in level ground walking in a
healthy elderly population.
AB - Tripping is presumed to be the principal cause for falls during walking. At
minimum toe clearance, the potential for trip-related falls is considered to be
highest. Thus, controlling minimum toe clearance is essential for walking without
tripping. In theory, the central nervous system should therefore give priority to
accurate control of the variability in minimum toe clearance, as compared to
other gait parameters, since people tend to only modify variability in any given
task if it interferes with the task performance. The aim of this study was to
determine whether elderly individuals show less increase in variability of
minimum toe clearance during a dual-task condition (where an increase of gait
variability is provoked), while allowing a larger range of variability in the
other gait parameters. Forty elderly participants walked back and forth on a 25 m
long track for five minutes. They then walked a second time performing an
additional cognitive task. The variability in stride time, stride length and
minimum toe clearance as well as dual-task costs of each gait parameter were
calculated for each walk. The variability in minimum toe clearance did not change
during dual task-walking, whereas the variability of stride length and stride
time increased, showing dual-task costs of about 66% and 84%, respectively. To
avoid additional detrimental load on the central nervous system, the modification
of task-irrelevant variability may be tolerated during dual-task conditions,
whereas minimum toe clearance is controlled with high priority.
PMID- 25128156
TI - Clinimetric properties of the Tinetti Mobility Test, Four Square Step Test,
Activities-specific Balance Confidence Scale, and spatiotemporal gait measures in
individuals with Huntington's disease.
AB - BACKGROUND AND PURPOSE: Individuals with Huntington's disease (HD) experience
balance and gait problems that lead to falls. Clinicians currently have very
little information about the reliability and validity of outcome measures to
determine the efficacy of interventions that aim to reduce balance and gait
impairments in HD. This study examined the reliability and concurrent validity of
spatiotemporal gait measures, the Tinetti Mobility Test (TMT), Four Square Step
Test (FSST), and Activities-specific Balance Confidence (ABC) Scale in
individuals with HD. METHODS: Participants with HD [n = 20; mean age +/- SD=50.9
+/- 13.7; 7 male] were tested on spatiotemporal gait measures and the TMT, FSST,
and ABC Scale before and after a six week period to determine test-retest
reliability and minimal detectable change (MDC) values. Linear relationships
between gait and clinical measures were estimated using Pearson's correlation
coefficients. RESULTS: Spatiotemporal gait measures, the TMT total and the FSST
showed good to excellent test-retest reliability (ICC > 0.75). MDC values were
0.30 m/s and 0.17 m/s for velocity in forward and backward walking respectively,
four points for the TMT, and 3s for the FSST. The TMT and FSST were highly
correlated with most spatiotemporal measures. The ABC Scale demonstrated lower
reliability and less concurrent validity than other measures. CONCLUSIONS: The
high test-retest reliability over a six week period and concurrent validity
between the TMT, FSST, and spatiotemporal gait measures suggest that the TMT and
FSST may be useful outcome measures for future intervention studies in ambulatory
individuals with HD.
PMID- 25128157
TI - An anti-apoptotic B-cell lymphoma-2 (BCL-2) from Channa striatus: Sequence
analysis and delayed and advanced gene expression in response to fungal,
bacterial and poly I:C induction.
AB - B-cell lymphoma-2 (BCL-2) is a suppressor of apoptosis and inhibits the caspase
dependent apoptosis pathway. In this study, we report molecular characterization
of a cDNA sequence encoded of BCL-2 from striped murrel, Channa striatus. A
partial cDNA sequence of CsBCL-2 was identified from the striped murrel cDNA
library during annotation. Subsequently, the full length CsBCL-2 cDNA sequence
was obtained by an internal sequencing method using a forward primer. The
sequence contains 699 nucleotide base pairs which encode 232 amino acid residues.
The domain and motif analysis revealed that the CsBCL-2 polypeptide consists of
BCL-2 homologous domain BH4 at the N-terminal region between 4 and 21 and the BCL
2 homologous domains BH1, BH2 and BH3 between 87 and 187. The CsBCL-2 polypeptide
sequence does not have a signal peptide region, but it consists of two novel
transmembrane regions at 134-152 and 209-226. The sequence analysis showed that
the CsBCL-2 has highest sequence identity (70%) with BCL-2 like protein 1 (BCL-2
L1) from pufferfish Takifugu rubripes. The phylogenetic analysis showed that the
CsBCL-2 was situated in the BCL-2 L1 fish clade. The secondary analysis showed
that the CsBCL-2 protein consists of 132 amino acid residues in the alpha-helical
region and 100 amino acid residues in the random coil region. The validated 3D
structure of CsBCL-2 showed the active residues Gly(135) and Arg(136) in the 7th
alpha-helical position, whereas Trp(178) is in the 9th alpha-helical region.
CsBCL-2 mRNA transcription is predominately present in spleen and is upregulated
upon being induced with fungus Aphanomyces invadans, bacteria Aeromonas
hydrophila, Escherichia coli LPS, Laminaria digitata beta-1,3-glucan and poly
I:C. Overall, the CsBCL-2 mRNA transcription results indicate the potential
involvement of CsBCL-2 in immune system of C. striatus. However, further research
at proteomic level is necessary to examine these predictions.
PMID- 25128158
TI - Porcine NOD1 polymorphisms with impaired ligand recognition and their
distribution in pig populations.
AB - Nucleotide-binding oligomerization domain 1 (NOD1) is a cytosolic pattern
recognition receptor that recognizes gamma-d-glutamyl-meso-diaminopimelic acid
(iE-DAP), a component of bacterial peptidoglycan. NOD1 is thought to be involved
in the immune homeostasis mediated by intestinal microbiota as well as the host
defense against infection. In this study, we identified 12 synonymous and nine
nonsynonymous single nucleotide polymorphisms (SNPs) in the coding sequence of
porcine NOD1 within major commercial breeds in the swine industry. Among the
nonsynonymous SNPs, two amino-acid alterations located in the leucine-rich
repeats region, glycine to glutamic acid at position 641 (G641E) and aspartic
acid to asparagine at position 918 (D918N), impaired iE-DAP-induced activation of
nuclear factor-kappaB. These alleles showed the recessive mode of inheritance and
therefore are likely to be maintained in pig populations at high frequencies.
These results suggest the possibility for improvement in disease resistance by
eliminating the G641E and D918N alleles of NOD1 from commercial pig populations.
PMID- 25128159
TI - Reply: To PMID 24529621.
PMID- 25128160
TI - Pulsatile airway obstruction found on ventilator pulmonary graphics.
PMID- 25128161
TI - Constipation: a Brown Herring.
PMID- 25128162
TI - Intimate partner violence increases adverse outcomes at birth and in early
infancy.
AB - OBJECTIVE: To determine the effect of intimate partner violence (IPV) on birth
outcomes and infant hospitalization. STUDY DESIGN: Hospitalization records for
the first 4 months of life for infants born in the Military Health System in 2006
2007 were linked to Family Advocacy Program-substantiated cases of IPV among
military parents. Adverse outcomes were identified using International
Classification of Diseases, Ninth Revision codes. Logistic regression modeling
calculated the OR of children exposed to IPV experiencing adverse outcomes.
RESULTS: A total of 204,546 infants were born during the study period. Among
these, 173,026 infants (85%) were linked to active duty military parents. 31,603
infants (18%) experienced adverse outcomes, and 3059 infants (1.8%) were born
into families with IPV. The infants exposed to IPV had a 31% increased odds of
experiencing adverse outcomes compared with infants without known IPV exposure.
IPV exposure increased the odds of the following outcomes: prematurity (OR, 1.45;
95% CI, 1.29-1.62), low birth weight (OR, 1.57; 95% CI, 1.25-1.97), respiratory
problems (OR, 1.17; 95% CI, 1.04-1.32), neonatal hospitalization (OR, 1.39; 95%
CI, 1.20-1.61), and postneonatal hospitalization (OR, 1.52; 95% CI, 1.29-1.81).
After controlling for prematurity and demographic variables, IPV exposure was
associated with low birth weight (OR, 1.52; 95% CI, 1.16-1.99), neonatal
hospitalization (OR, 1.24; 95% CI, 1.02-1.49), and postneonatal hospitalization
(OR, 1.27; 95% CI, 1.03-1.56). CONCLUSION: Infants exposed to IPV are more likely
to experience adverse birth outcomes and infant hospitalization. Routinely
addressing IPV during prenatal and early pediatric visits may potentially prevent
these adverse outcomes.
PMID- 25128163
TI - Mapping human resources for eye health in 21 countries of sub-Saharan Africa:
current progress towards VISION 2020.
AB - BACKGROUND: Development of human resources for eye health (HReH) is a major focus
of the Global Action Plan 2014 to 2019 to reduce the prevalence of avoidable
visual impairment by 25% by the year 2019. The eye health workforce is thought to
be much smaller in sub-Saharan Africa than in other regions of the world but data
to support this for policy-making is scarce. We collected HReH and cataract
surgeries data from 21 countries in sub-Sahara to estimate progress towards key
suggested population-based VISION 2020 HReH indicators and cataract surgery rates
(CSR) in 2011. METHODS: Routinely collected data on practitioner and surgery
numbers in 2011 was requested from national eye care coordinators via electronic
questionnaires. Telephone and e-mail discussions were used to determine data
collection strategies that fit the national context and to verify reported data
quality. Information was collected on six practitioner cadres: ophthalmologists,
cataract surgeons, ophthalmic clinical officers, ophthalmic nurses, optometrists
and 'mid-level refractionists' and combined with publicly available population
data to calculate practitioner to population ratios and CSRs. Associations with
development characteristics were conducted using Wilcoxon rank sum tests and
Spearman rank correlations. RESULTS: HReH data was not easily available. A
minority of countries had achieved the suggested VISION 2020 targets in 2011;
five countries for ophthalmologists/cataract surgeons, four for ophthalmic
nurses/clinical officers and two for CSR. All countries were below target for
optometrists, even when other cadres who perform refractions as a primary duty
were considered. The regional (sample) ratio for surgeons (ophthalmologists and
cataract surgeons) was 2.9 per million population, 5.5 for ophthalmic clinical
officers and nurses, 3.7 for optometrists and other refractionists, and 515 for
CSR. A positive correlation between GDP and CSR as well as many practitioner
ratios was observed (CSR P = 0.0042, ophthalmologists P = 0.0034, cataract
surgeons, ophthalmic nurses and optometrists 0.1 > P > 0.05). CONCLUSIONS: With
only a minority of countries in our sample having reached suggested ophthalmic
cadre targets and none having reached targets for refractionists in 2011,
substantially more targeted investment in HReH may be needed for VISION 2020 aims
to be achieved in sub-Saharan Africa.
PMID- 25128164
TI - Aldosterone augments Na+-induced reduction of cardiac norepinephrine reuptake.
AB - Impairment of the cardiac norepinephrine (NE) reuptake by the neuronal NE
transporter contributes to enhanced cardiac NE net release in congestive heart
failure. Elevated plasma levels of aldosterone (AL) promote sympathetic
overstimulation in failing hearts by unclear mechanisms. Our aim was to evaluate
if elevated AL and/or alterations in Na(+) intake regulate cardiac NE reuptake.
To test the effects of AL and Na(+) on cardiac NE reuptake, Wistar rats were fed
a normal-salt (NS) diet (0.2% NaCl), a low-salt (LS) diet (0.015% NaCl), or a
high-salt (HS) diet (8% NaCl). Another group of animals received AL infusion
alone (0.75 MUg/h) or AL infusion plus HS diet. Specific cardiac [(3)H]NE uptake
via the NE transporter in a Langendorff preparation and AL plasma levels were
measured at different time points between 5 and 42 days of treatment. To compare
these findings from healthy animals with a disease model, Dahl salt-sensitive
rats were investigated as a model of congestive heart failure with endogenously
elevated AL. In summary, neither exogenous nor endogenous elevations of AL alone
were sufficient to reduce cardiac NE reuptake. Only the HS diet induced a
reduction of NE reuptake by 26%; additional infusion of AL augmented this effect
to a further reduction of NE reuptake by 36%. In concordance, Dahl salt-sensitive
rats treated with a HS diet displayed elevated AL and a marked reduction of NE
reuptake. We conclude that exogenous or endogenous AL elevations alone do not
reduce cardiac NE reuptake, but AL serves as an additional factor that negatively
regulates cardiac NE reuptake in concert with HS intake.
PMID- 25128165
TI - Slow and deep respiration suppresses steady-state sympathetic nerve activity in
patients with chronic heart failure: from modeling to clinical application.
AB - Influences of slow and deep respiration on steady-state sympathetic nerve
activity remain controversial in humans and could vary depending on disease
conditions and basal sympathetic nerve activity. To elucidate the respiratory
modulation of steady-state sympathetic nerve activity, we modeled the dynamic
nature of the relationship between lung inflation and muscle sympathetic nerve
activity (MSNA) in 11 heart failure patients with exaggerated sympathetic outflow
at rest. An autoregressive exogenous input model was utilized to simulate entire
responses of MSNA to variable respiratory patterns. In another 18 patients, we
determined the influence of increasing tidal volume and slowing respiratory
frequency on MSNA; 10 patients underwent a 15-min device-guided slow respiration
and the remaining 8 had no respiratory modification. The model predicted that a 1
liter, step increase of lung volume decreased MSNA dynamically; its nadir (-33 +/
22%) occurred at 2.4 s; and steady-state decrease (-15 +/- 5%), at 6 s.
Actually, in patients with the device-guided slow and deep respiration,
respiratory frequency effectively fell from 16.4 +/- 3.9 to 6.7 +/- 2.8/min (P <
0.0001) with a concomitant increase in tidal volume from 499 +/- 206 to 1,177 +/-
497 ml (P < 0.001). Consequently, steady-state MSNA was decreased by 31% (P <
0.005). In patients without respiratory modulation, there were no significant
changes in respiratory frequency, tidal volume, and steady-state MSNA. Thus slow
and deep respiration suppresses steady-state sympathetic nerve activity in
patients with high levels of resting sympathetic tone as in heart failure.
PMID- 25128166
TI - AMPK activation by glucagon-like peptide-1 prevents NADPH oxidase activation
induced by hyperglycemia in adult cardiomyocytes.
AB - Exposure of cardiomyocytes to high glucose concentrations (HG) stimulates
reactive oxygen species (ROS) production by NADPH oxidase (NOX2). NOX2 activation
is triggered by enhanced glucose transport through a sodium-glucose cotransporter
(SGLT) but not by a stimulation of glucose metabolism. The aim of this work was
to identify potential therapeutic approaches to counteract this glucotoxicity. In
cultured adult rat cardiomyocytes incubated with 21 mM glucose (HG), AMP
activated protein kinase (AMPK) activation by A769662 or phenformin nearly
suppressed ROS production. Interestingly, glucagon-like peptide 1 (GLP-1), a new
antidiabetic drug, concomitantly induced AMPK activation and prevented the HG
mediated ROS production (maximal effect at 100 nM). alpha2-AMPK, the major
isoform expressed in cardiomyocytes (but not alpha1-AMPK), was activated in
response to GLP-1. Anti-ROS properties of AMPK activators were not related to
changes in glucose uptake or glycolysis. Using in situ proximity ligation assay,
we demonstrated that AMPK activation prevented the HG-induced p47phox
translocation to caveolae, whatever the AMPK activators used. NOX2 activation by
either alpha-methyl-d-glucopyranoside, a glucose analog transported through SGLT,
or angiotensin II was also counteracted by GLP-1. The crucial role of AMPK in
limiting HG-mediated NOX2 activation was demonstrated by overexpressing a
constitutively active form of alpha2-AMPK using adenoviral infection. This
overexpression prevented NOX2 activation in response to HG, whereas GLP-1 lost
its protective action in alpha2-AMPK-deficient mouse cardiomyocytes. Under HG,
the GLP-1/AMPK pathway inhibited PKC-beta2 phosphorylation, a key element
mediating p47phox translocation. In conclusion, GLP-1 induces alpha2-AMPK
activation and blocks HG-induced p47phox translocation to the plasma membrane,
thereby preventing glucotoxicity.
PMID- 25128167
TI - Regulatory T cells are recruited in the infarcted mouse myocardium and may
modulate fibroblast phenotype and function.
AB - Regulatory T cells (Tregs) play a pivotal role in suppressing immune responses
regulating behavior and gene expression in effector T cells, macrophages, and
dendritic cells. Tregs infiltrate the infarcted myocardium; however, their role
the inflammatory and reparative response after myocardial infarction remains
poorly understood. We used FoxP3(EGFP) reporter mice to study Treg trafficking in
the infarcted heart and examined the effects of Treg depletion on postinfarction
remodeling using an anti-CD25 antibody. Moreover, we investigated the in vitro
effects of Tregs on cardiac fibroblast phenotype and function. Low numbers of
Tregs infiltrated the infarcted myocardium after 24-72 h of reperfusion. Treg
depletion had no significant effects on cardiac dysfunction and scar size after
reperfused myocardial infarction but accelerated ventricular dilation and
accentuated apical remodeling. Enhanced myocardial dilation in Treg-depleted
animals was associated with increased expression of chemokine (C-C motif) ligand
2 and accentuated macrophage infiltration. In vitro, Tregs modulated the cardiac
fibroblast phenotype, reducing expression of alpha-smooth muscle actin,
decreasing expression of matrix metalloproteinase-3, and attenuating contraction
of fibroblast-populated collagen pads. Our findings suggest that endogenous Tregs
have modest effects on the inflammatory and reparative response after myocardial
infarction. However, the anti-inflammatory and matrix-preserving properties of
Tregs may suggest a role for Treg-based cell therapy in the attenuation of
adverse postinfarction remodeling.
PMID- 25128168
TI - Aging impairs smooth muscle-mediated regulation of aortic stiffness: a defect in
shock absorption function?
AB - Increased aortic stiffness is an early and independent biomarker of
cardiovascular disease. Here we tested the hypothesis that vascular smooth muscle
cells (VSMCs) contribute significantly to aortic stiffness and investigated the
mechanisms involved. The relative contributions of VSMCs, focal adhesions (FAs),
and matrix to stiffness in mouse aorta preparations at optimal length and with
confirmed VSMC viability were separated by the use of small-molecule inhibitors
and activators. Using biomechanical methods designed for minimal perturbation of
cellular function, we directly quantified changes with aging in aortic material
stiffness. An alpha adrenoceptor agonist, in the presence of N(G)-nitro-l
arginine methyl ester (l-NAME) to remove interference of endothelial nitric
oxide, increases stiffness by 90-200% from baseline in both young and old mice.
Interestingly, increases are robustly suppressed by the Src kinase inhibitor PP2
in young but not old mice. Phosphotyrosine screening revealed, with aging, a
biochemical signature of markedly impaired agonist-induced FA remodeling
previously associated with Src signaling. Protein expression measurement
confirmed a decrease in Src expression with aging. Thus we report here an
additive model for the in vitro biomechanical components of the mouse aortic wall
in which 1) VSMCs are a surprisingly large component of aortic stiffness at
physiological lengths and 2) regulation of the VSMC component through FA
signaling and hence plasticity is impaired with aging, diminishing the aorta's
normal shock absorption function in response to stressors.
PMID- 25128169
TI - Prolonged uterine artery nitric oxide synthase inhibition modestly alters basal
uteroplacental vasodilation in the last third of ovine pregnancy.
AB - Mechanisms regulating uteroplacental blood flow (UPBF) in pregnancy remain
unclear, but they likely involve several integrated signaling systems.
Endothelium-derived nitric oxide (NO) is considered an important contributor, but
the extent of its involvement is unclear. Bolus intra-arterial infusions of nitro
l-arginine methyl ester (l-NAME) modestly decrease ovine basal UPBF; however, the
doses and duration of infusion may have been insufficient. We, therefore,
examined prolonged uterine artery (UA) NO synthase inhibition with l-NAME
throughout the last third of ovine pregnancy by performing either continuous 30
min UA infusion dose responses (n = 4) or 72-h UA infusions (0.01 mg/ml) at 104
108, 118-125, and 131-137 days of gestation (n = 7) while monitoring mean
arterial pressure (MAP), heart rate (HR), and UPBF. Uteroplacental vascular
resistance (UPVR) was calculated, and uterine cGMP synthesis was measured. Thirty
minute UA l-NAME infusions did not dose dependently decrease UPBF, increase UPVR,
or decrease uterine cGMP synthesis (P > 0.1); however, MAP rose and HR fell
modestly. Prolonged continuous 72-h UA l-NAME infusions decreased UPBF ~32%,
increased UPVR ~68% (P <= 0.001), and decreased uterine cGMP synthesis 70% at 54
72 h (P <= 0.004); the noninfused uterine horn was unaffected. These findings
were associated with ~10% increases in MAP and decreases in HR that were greater
at 104-108 than 118-125 and 131-137 days of gestation (P = 0.006). Although
uterine and UA NO and cGMP synthesis increase severalfold during ovine pregnancy,
they contribute modestly to the maintenance and rise in UPBF in the last third of
gestation. Thus, local UA NO may primarily modulate vasoconstrictor responses.
Notably, the systemic vasculature appears more sensitive than the uterine
vasculature to NO synthase inhibition.
PMID- 25128170
TI - Resveratrol modulates the angiogenic response to exercise training in skeletal
muscles of aged men.
AB - In animal studies, the polyphenol resveratrol has been shown to influence several
pathways of importance for angiogenesis in skeletal muscle. The aim of the
present study was to examine the angiogenic effect of resveratrol supplementation
with parallel exercise training in aged men. Forty-three healthy physically
inactive aged men (65 +/- 1 yr) were divided into 1) a training group that
conducted 8 wk of intense exercise training where half of the subjects received a
daily intake of either 250 mg trans-resveratrol (n = 14) and the other half
received placebo (n = 13) and 2) a nontraining group that received either 250 mg
trans-resveratrol (n = 9) or placebo (n = 7). The group that trained with placebo
showed a ~20% increase in the capillary-to-fiber ratio, an increase in muscle
protein expression of VEGF, VEGF receptor-2, and tissue inhibitor of matrix
metalloproteinase (TIMP-1) but unaltered thrombospodin-1 levels. Muscle
interstitial VEGF and thrombospodin-1 protein levels were unchanged after the
training period. The group that trained with resveratrol supplementation did not
show an increase in the capillary-to-fiber ratio or an increase in muscle VEGF
protein. Muscle TIMP-1 protein levels were lower in the training and resveratrol
group than in the training and placebo group. Both training groups showed an
increase in forkhead box O1 protein. In nontraining groups, TIMP-1 protein was
lower in the resveratrol-treated group than the placebo-treated group after 8 wk.
In conclusion, these data show that exercise training has a strong angiogenic
effect, whereas resveratrol supplementation may limit basal and training-induced
angiogenesis.
PMID- 25128172
TI - Hyperbilirubinemia modulates myocardial function, aortic ejection, and ischemic
stress resistance in the Gunn rat.
AB - Mildly elevated circulating unconjugated bilirubin (UCB) is associated with
protection against hypertension and ischemic heart disease. We assessed whether
endogenously elevated bilirubin in Gunn rats modifies cardiovascular function and
resistance to ischemic insult. Hearts were assessed ex vivo (Langendorff
perfusion) and in vivo (Millar catheterization and echocardiography), and left
ventricular myocardial gene expression was measured via quantitative real-time
PCR. Ex vivo analysis revealed reduced intrinsic contractility in the Gunn
myocardium (+dP/dt: 1,976 +/- 622 vs. 2,907 +/- 334 mmHg/s, P < 0.01; -dP/dt:
1,435 +/- 372 vs. -2,234 +/- 478 mmHg/s, P < 0.01), which correlated positively
with myocardial UCB concentration (P < 0.05). In vivo analyses showed no changes
in left ventricular contractile parameters and ejection (fractional shortening
and ejection fraction). However, Gunn rats exhibited reductions in the rate of
aortic pressure development (3,008 +/- 461 vs. 4,452 +/- 644 mmHg/s, P < 0.02),
mean aortic velocity (439 +/- 64 vs. 644 +/- 62 mm/s, P < 0.01), and aortic
volume time integral pressure gradient (2.32 +/- 0.65 vs. 5.72 +/- 0.74 mmHg, P <
0.01), in association with significant aortic dilatation (12-24% increase in
aortic diameter, P < 0.05). Ex vivo Gunn hearts exhibited improved ventricular
function after 35 min of ischemia and 90 min of reperfusion (63 +/- 14 vs. 35 +/-
12%, P < 0.01). These effects were accompanied by increased glutathione
peroxidase and reduced superoxide dismutase and phospholamban gene expression in
Gunn rat myocardium (P < 0.05). These data collectively indicate that
hyperbilirubinemia in Gunn rats 1) reduces intrinsic cardiac contractility, which
is compensated for in vivo; 2) induces aortic dilatation, which may beneficially
influence aortic ejection velocities and pressures; and 3) may improve myocardial
stress resistance in association with beneficial transcriptional changes. These
effects may contribute to protection from cardiovascular disease with elevated
bilirubin.
PMID- 25128171
TI - Myofilament dysfunction contributes to impaired myocardial contraction in the
infarct border zone.
AB - After myocardial infarction, a poorly contracting nonischemic border zone forms
adjacent to the infarct. The cause of border zone dysfunction is unclear. The
goal of this study was to determine the myofilament mechanisms involved in
postinfarction border zone dysfunction. Two weeks after anteroapical infarction
of sheep hearts, we studied in vitro isometric and isotonic contractions of
demembranated myocardium from the infarct border zone and a zone remote from the
infarct. Maximal force development (Fmax) of the border zone myocardium was
reduced by 31 +/- 2% versus the remote zone myocardium (n = 6/group, P < 0.0001).
Decreased border zone Fmax was not due to a reduced content of contractile
material, as assessed histologically, and from myosin content. Furthermore,
decreased border zone Fmax did not involve altered cross-bridge kinetics, as
assessed by muscle shortening velocity and force development kinetics. Decreased
border zone Fmax was associated with decreased cross-bridge formation, as
assessed from muscle stiffness in the absence of ATP where cross-bridge formation
should be maximized (rigor stiffness was reduced 34 +/- 6%, n = 5, P = 0.011 vs.
the remote zone). Furthermore, the border zone myocardium had significantly
reduced phosphorylation of myosin essential light chain (ELC; 41 +/- 10%, n = 4,
P < 0.05). However, for animals treated with doxycycline, an inhibitor of matrix
metalloproteinases, rigor stiffness and ELC phosphorylation were not reduced in
the border zone myocardium, suggesting that doxycycline had a protective effect.
In conclusion, myofilament dysfunction contributes to postinfarction border zone
dysfunction, myofilament dysfunction involves impaired cross-bridge formation and
decreased ELC phosphorylation, and matrix metalloproteinase inhibition may be
beneficial for limiting postinfarct border zone dysfunction.
PMID- 25128173
TI - Type 2 diabetes: increased expression and contribution of IKCa channels to
vasodilation in small mesenteric arteries of ZDF rats.
AB - Impaired endothelial function, which is dysregulated in diabetes, also precedes
hypertension. We hypothesized that in Type 2 diabetes, the impaired endothelium
dependent relaxation is due to a loss of endothelium-derived hyperpolarization
(EDH) that is regulated by impaired ion channel function. Zucker diabetic fatty
(ZDF), Zucker heterozygote, and homozygote lean control rats were used as the
experimental models in our study. Third-order mesenteric arteries were dissected
and mounted on a pressure myograph; mRNA was quantified by RT-PCR and channel
proteins by Western blotting. Under nitric oxide (NO) synthase and cyclooxygenase
inhibition, endothelial stimulation with ACh fully relaxes control but not
diabetic arteries. In contrast, when small-conductance calcium-activated
potassium (KCa) channels and intermediate- and large-conductance KCa (I/BKCa) are
inhibited with apamin and charybdotoxin, NO is able to compensate for ACh-induced
relaxation in control but not in diabetic vessels. After replacement of
charybdotoxin with 1-[(2-chlorophenyl)diphenylmethyl]-(1)H-pyrazole (TRAM-34;
IKCa inhibitor), ACh-induced relaxation in diabetic animals is attenuated.
Specific inhibition with TRAM-34 or charybdotoxin attenuates ACh relaxation in
diabetes. Stimulation with 1-ethyl-2-benzimidazolinone (IKCa activator) shows a
reduced relaxation in diabetes. Activation of BKCa with 1,3-dihydro-1-[2-hydroxy
5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-(2)H-benzimidazol-2-one NS619
leads to similar relaxations of control and diabetic arteries. RT-PCR and Western
blot analysis demonstrate elevated mRNA and protein expression levels of IKCa in
diabetes. Our results suggest that the compensatory effect of NO and EDH
associated, endothelium-dependent relaxation is reduced in ZDF rats. Specific
blockade of IKCa with TRAM-34 reduces NO and EDH-type relaxation in diabetic
rats, indicating an elevated contribution of IKCa in diabetic small mesenteric
artery relaxation. This finding correlates with increased IKCa mRNA and protein
expression in this vessel.
PMID- 25128174
TI - Unexpected maturation of PI3K and MAPK-ERK signaling in fetal ovine
cardiomyocytes.
AB - In the first two-thirds of gestation, ovine fetal cardiomyocytes undergo mitosis
to increase cardiac mass and accommodate fetal growth. Thereafter, some myocytes
continue to proliferate while others mature and terminally differentiate into
binucleated cells. At term (145 days gestational age; dGA) about 60% of
cardiomyocytes become binucleated and exit the cell cycle under hormonal control.
Rising thyroid hormone (T3) levels near term (135 dGA) inhibit proliferation and
stimulate maturation. However, the degree to which intracellular signaling
patterns change with age in response to T3 is unknown. We hypothesized that in
vitro activation of ERK, Akt, and p70(S6K) by two regulators of cardiomyocyte
cell cycle activity, T3 and insulin like growth factor-1 (IGF-1), would be
similar in cardiomyocytes at gestational ages 100 and 135 dGA. IGF-1 and T3 each
independently stimulated phosphorylation of ERK, Akt, and p70(S6K) in cells at
both ages. In the younger mononucleated myocytes, the phosphorylation of ERK and
Akt was reduced in the presence of IGF-1 and T3. However, the same hormone
combination led to a dramatic twofold increase in the phosphorylation of these
signaling proteins in the 135 dGA cardiomyocytes-even in cells that were not
proliferating. In the older cells, both mono- and binucleated cells were
affected. In conclusion, fetal ovine cardiomyocytes undergo profound maturation
related changes in signaling in response to T3 and IGF-1, but not to either
factor alone. Differences in age-related response are likely to be related to
milestones in fetal cardiac development as the myocardium prepares for ex utero
life.
PMID- 25128175
TI - Mitochondrial depolarization and electrophysiological changes during ischemia in
the rabbit and human heart.
AB - Instability of the inner mitochondrial membrane potential (DeltaPsim) has been
implicated in electrical dysfunction, including arrhythmogenesis during ischemia
reperfusion. Monitoring DeltaPsim has led to conflicting results, where
depolarization has been reported as sporadic and as a propagating wave. The
present study was designed to resolve the aforementioned difference and determine
the unknown relationship between DeltaPsim and electrophysiology. We developed a
novel imaging modality for simultaneous optical mapping of DeltaPsim and
transmembrane potential (Vm). Optical mapping was performed using potentiometric
dyes on preparations from 4 mouse hearts, 14 rabbit hearts, and 7 human hearts.
Our data showed that during ischemia, DeltaPsim depolarization is sporadic and
changes asynchronously with electrophysiological changes. Spatially, DeltaPsim
depolarization was associated with action potential duration shortening but not
conduction slowing. Analysis of focal activity indicated that DeltaPsim is not
different within the myocardium where the focus originates compared with normal
ventricular tissue. Overall, our data suggest that during ischemia, mitochondria
maintain their function at the expense of sarcolemmal electrophysiology, but
DeltaPsim depolarization does not have a direct association to ischemia-induced
arrhythmias.
PMID- 25128176
TI - Calibrated delivery drape versus indirect gravimetric technique for the
measurement of blood loss after delivery: a randomized trial.
AB - BACKGROUND: Trials of interventions for PPH prevention and treatment rely on
different measurement methods for the quantification of blood loss and
identification of PPH. This study's objective was to compare measures of blood
loss obtained from two different measurement protocols frequently used in
studies. METHODS: Nine hundred women presenting for vaginal delivery were
randomized to a direct method (a calibrated delivery drape) or an indirect method
(a shallow bedpan placed below the buttocks and weighing the collected blood and
blood-soaked gauze/pads). Blood loss was measured from immediately after delivery
for at least one hour or until active bleeding stopped. RESULTS: Significantly
greater mean blood loss was recorded by the direct than by the indirect
measurement technique (253.9 mL and 195.3 mL, respectively; difference = 58.6 mL
(95% CI: 31-86); p < 0.001). Almost twice as many women in the direct than in the
indirect group measured blood loss > 500 mL (8.7% vs. 4.7%, p = 0.02).
CONCLUSIONS: The study suggests a real and significant difference in blood loss
measurement between these methods. Research using blood loss measurement as an
endpoint needs to be interpreted taking measurement technique into consideration.
TRIAL REGISTRATION: This study has been registered at clinicaltrials.gov as
NCT01885845.
PMID- 25128177
TI - Long-term increased risk of unemployment after young stroke: a long-term follow
up study.
AB - OBJECTIVE: To investigate the prevalence, excess risk, and risk factors of
unemployment in patients after a TIA, ischemic stroke, or intracerebral
hemorrhage at ages 18 through 50 years, compared with nationwide controls.
METHODS: We performed a hospital-based cohort study among 694 patients, aged 18
50 years, with a first-ever TIA, ischemic stroke, or intracerebral hemorrhage.
After a mean follow-up duration of 8.1 (SD 7.7) years, we used logistic
regression analysis to calculate odds ratio (OR) with 95% confidence interval
(CI) for being unemployed as a young stroke patient, compared with the Dutch
population of vocational age (n = 7,803,000), with subsequent assessment of risk
factors of unemployment. RESULTS: Young stroke patients had a higher risk of
being unemployed than their peers in the Dutch population: women OR 2.3 (1.8
2.9), men OR 3.2 (2.5-4.0). A higher NIH Stroke Scale score at admission (OR 1.1
[95% CI 1.0-1.1]) and a longer follow-up duration (middle tertile OR 2.8 [95% CI
1.7-4.7], upper tertile OR 3.4 [95% CI 1.9-6.1]) were associated with a higher
risk of being unemployed. CONCLUSION: Young stroke patients had a 2-3 times
higher risk of unemployment after 8 years of follow-up. Return-to-work programs
should be developed, adjusted, and evaluated in order to diminish the negative
effects that unemployment can have on patients' life satisfaction and to limit
the socioeconomic consequences.
PMID- 25128178
TI - Studying the brain: Complexities at every level.
PMID- 25128179
TI - Predictions, perception, and a sense of self.
AB - In recent years there has been a paradigm shift in theoretical neuroscience in
which the brain-as a passive processor of sensory information-is now considered
an active organ of inference, generating predictions and hypotheses about the
causes of its sensations. In this commentary, we try to convey the basic ideas
behind this perspective, describe their neurophysiologic underpinnings, and
highlight the potential importance of this formulation for clinical neuroscience.
The formalism it provides-and the implementation of active inference in the brain
may have the potential to reveal aspects of functional neuroanatomy that are
compromised in conditions ranging from Parkinson disease to schizophrenia. In
particular, many neurologic and neuropsychiatric conditions may be understandable
in terms of a failure to modulate the postsynaptic gain of neuronal populations
reporting prediction errors during action and perception. From the perspective of
the predictive brain, this represents a failure to encode the precision of-or
confidence in-sensory information. We propose that the predictive or inferential
perspective on brain function offers novel insights into brain diseases.
PMID- 25128180
TI - Subclinical leukodystrophy and infertility in a man with a novel homozygous CLCN2
mutation.
PMID- 25128181
TI - Life after stroke: Beyond medications.
PMID- 25128182
TI - Central poststroke pain in young ischemic stroke survivors in the Helsinki Young
Stroke Registry.
AB - OBJECTIVE: We describe the frequency, duration, clinical characteristics, and
radiologic correlates of central poststroke pain (CPSP) in young ischemic stroke
survivors in a prospective study setting. METHODS: A questionnaire of pain and
sensory abnormalities and EQ-5D quality-of-life questionnaire were sent to all
824 surviving and eligible patients of the Helsinki Young Stroke Registry.
Patients (n = 58) with suspected CPSP were invited to a clinical visit and filled
in the PainDETECT, Brief Pain Inventory, and Beck Depression Inventory
questionnaires. RESULTS: Of the included 824 patients, 49 had CPSP (5.9%), 246
patients (29.9%) had sensory abnormality without CPSP, and 529 patients (64.2%)
had neither sensory abnormality nor CPSP. The median follow-up time from stroke
was 8.5 years (interquartile range 5.0-12.1). Patients with CPSP had low quality
of life compared to those with sensory abnormality without CPSP (p = 0.007) as
well as to those with no sensory abnormality and no CPSP (p < 0.001). Forty (82%)
of the patients with CPSP had concomitant other pain. CPSP was associated with
moderate (p < 0.001) and severe (p < 0.001) stroke symptoms, but there was no
difference in age at stroke onset or subtype of stroke according to the TOAST
classification between the groups. Stroke localization was not correlated with
CPSP. CONCLUSIONS: Late persistent CPSP was found in 5.9% of young stroke
survivors and was associated with concomitant other pain, impaired quality of
life, and moderate or severe stroke symptoms.
PMID- 25128183
TI - Course of psychiatric symptoms and global cognition in early Parkinson disease.
AB - OBJECTIVE: To evaluate the course and predictors of neuropsychiatric symptoms
(NPS) and cognition in patients with de novo Parkinson disease (PD). METHODS:
Cross-sectional study of the cohort of de novo, untreated (at enrollment)
patients with PD and healthy controls (HCs) from the Parkinson's Progression
Markers Initiative. Participants have serial assessments of global cognition and
symptoms of depression, anxiety, psychosis, impulse control disorders (ICDs),
sleep and wakefulness, apathy, and fatigue. Available data up to 24 months of
follow-up were included. RESULTS: The available sample size was as follows:
baseline (PD = 423, HCs = 196), 12 months (PD = 261, HCs = 145), and 24 months
(PD = 96, HCs = 83). Patients with PD experienced more depression, fatigue,
apathy, and anxiety than HCs at all time points, and apathy (p = 0.001) and
psychosis (p = 0.003) increased over time in patients with PD. Approximately two
thirds of patients with PD who screened positive for depression at any given
visit were not taking an antidepressant. The Montreal Cognitive Assessment score
decreased significantly over time in patients with PD (p < 0.001), but the change
was comparable to that in HCs. At the 24-month visit, 44% of patients had been on
dopamine replacement therapy (DRT) for at least 1 year, and this group reported
more incident ICDs (p = 0.009) and excessive daytime sleepiness (p = 0.03).
CONCLUSION: Multiple NPS are more common in de novo, untreated patients with PD
compared with the general population, but they also remain relatively stable in
early disease, while global cognition slightly deteriorates. In contrast,
initiation of DRT is associated with increasing frequency of several other NPS.
PMID- 25128184
TI - Ultra-performance liquid chromatography-quadrupole?time-of- flight mass
spectrometry with multivariate statistical analysis for exploring potential
chemical markers to distinguish between raw and processed Rheum palmatum.
AB - BACKGROUND: The long term use of Rheum palmatum for the treatment of diseases
associated with chronic hepatitis and renal failure can lead to liver and kidney
damage. To reduce the toxicity of R. palmatum and alleviate any symptoms of
decanta and celialgia, the raw material has been subjected to a specific process
prior to its use for hundreds of years. Despite its extensive use in medicine,
very little is currently known about the nature of the components present in this
material in terms of their efficacy and overall toxicity, and the effect that
processing has on the levels of these components in the processed material. The
aim of this investigation was to explore potential differences in the chemical
markers between batches of raw and processed R. palmatum and to develop a deeper
understanding of the underlying mechanisms responsible for the enhanced efficacy
and reduced toxicity of the processed material. METHODS: Raw and processed R.
palmatum samples were analyzed by ultra-performance liquid chromatography
quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) coupled with
multivariate statistical analysis using principal component analysis (PCA) and
orthogonal partial least square discriminant analysis (OPLS-DA). RESULTS: The
emodin-8-O-glucoside, emodin-O-glucoside, catechin-glucopyranoside, gallic acid-3
O-glucoside, torachrysone, and chrysophanol dimethyl ether were rapidly explored
as representative markers to distinguish for the first time between the raw and
processed R. palmatum material. Among the potential chemical markers, Emodin-8-O
glucoside and gallic acid-3-O-glucoside were determined to be the best markers
for the raw and processed R. palmatum. CONCLUSION: UPLC/Q-TOF-MS with
multivariate statistical analysis represents an efficient method for exploring
the chemical markers in the raw and processed R. palmatum material, as well as
investigating the mechanisms associated with the processing, quality control, and
safe application of R. palmatum.
PMID- 25128186
TI - Family-based interventions for substance misuse: a systematic review of
systematic reviews--protocol.
AB - BACKGROUND: Worldwide, there are an estimated 15 million individuals with drug
use disorders and over five times as many with alcohol use disorders (WHO 1:2,
2005). Most individuals with substance misuse have families who are affected.
Initial scoping searches identified an expanse of broad and disparate studies and
reviews on the family interventions for substance misuse. This systematic review
of systematic reviews aims to bring together the expanse of research on the
effectiveness of family-based interventions in substance misuse.Initial scoping
searches identified an expanse of broad and disparate studies and reviews on the
family interventions for substance misuse. This systematic review of systematic
reviews aims to bring together the expanse of research on the effectiveness of
family-based interventions in substance misuse. METHODS: Extensive electronic and
manual searches will be undertaken. Screening, data extraction and quality
assessment will be undertaken by two reviewers with disagreements resolved
through discussion.The inclusion criteria will be that the study is a
systematically undertaken review, the population is individuals with substance
misuse problems and the interventions include a family-focused component. Reviews
that focus on prevention rather than treatment will be excluded. The reviews will
be assessed for quality and relevance. The evidence from included systematic
reviews will be mapped by focus of intervention (promoting engagement of user
into treatment/joint involvement in treatment of user/treating family member in
own right) for both adults and adolescents for drug and/or alcohol misusers to
allow assessment of the density of available evidence. The higher-quality, up-to
date evidence for each domain will be identified and described, and conclusions
will be drawn with limitations of the evidence highlighted. DISCUSSION: This
systematic review of systematic reviews will be an efficient and robust way of
looking at the current state of the evidence in the field of family-based
interventions for substance misuse. It will evaluate all the available systematic
review-level literature to report on the effectiveness of family-based
psychological interventions in improving substance-related outcomes and improving
health and wellbeing of substance misusers and/or their families. This will
inform future treatment policies and commissioning decisions.In addition, it will
identify areas of poor quality, inconsistency and gaps in the evidence base for
family-based psychological interventions in substance misuse with respect to
secondary evidence in order to inform future research. SYSTEMATIC REVIEW
REGISTRATION: PROSPERO CRD42014006834.
PMID- 25128185
TI - Recruitment of young adults into a randomized controlled trial of weight gain
prevention: message development, methods, and cost.
AB - BACKGROUND: Young adulthood (age 18 to 35) is a high-risk period for unhealthy
weight gain. Few studies have recruited for prevention of weight gain,
particularly in young adults. This paper describes the recruitment protocol used
in the Study of Novel Approaches to Prevention (SNAP). METHODS: We conducted
extensive formative work to inform recruitment methods and message development.
We worked with a professional marketing firm to synthesize major themes and
subsequently develop age-appropriate messages for recruitment. A variety of
approaches and channels were used across two clinical centers to recruit young
adults who were normal or overweight (body mass index (BMI) 21 to 30 kg/m2) for a
3-year intervention designed to prevent weight gain. We tracked recruitment
methods, yields, and costs by method. Logistic regression was used to identify
recruitment methods that had the highest relative yield for subgroups of interest
with covariate adjustments for clinic. RESULTS: The final sample of 599
participants (27% minority, 22% male) was recruited over a 19-month period of
sustained efforts. About 10% of those who initially expressed interest via a
screening website were randomized. The most common reason for ineligibility was
already being obese (BMI >30 kg/m2). The top two methods for recruitment were
mass mailing followed by email; together they were cited by 62% of those
recruited. Television, radio, paid print advertising, flyers and community events
each yielded fewer than 10% of study participants. Email was the most cost
effective method per study participant recruited. CONCLUSIONS: These findings can
guide future efforts to recruit young adults and for trials targeting weight gain
prevention. TRIAL REGISTRATION: ClinicalTrials.gov NCT01183689 (registered 13
August 2010).
PMID- 25128187
TI - Rare embryonal rhabdomyosarcoma of external acoustic canal: a case report and
literature review.
AB - Embryonal rhabdomyosarcoma of external ear canal is very rare, even in the
pediatric population. We report an embryonal rhabdomyosarcoma of external
acoustic canal, occurring in a 12-year-old Chinese girl who presented with left
ear canal mass. Wide local excision of the mass was done under local anesthesia.
Histopathological examination revealed the diagnosis. She then underwent 20
cycles of radiotherapy. CECT scan post treatment showed clearance of tumor cell.
Now, patient is disease free for 5 years. We believe that early diagnosis
followed by complete resection of the tumor with clear margin and radiotherapy
improves the prognosis of the disease.
PMID- 25128188
TI - Prediction of clinical manifestations of transurethral resection syndrome by
preoperative ultrasonographic estimation of prostate weight.
AB - BACKGROUND: This study aimed to investigate the relationship between preoperative
estimated prostate weight on ultrasonography and clinical manifestations of
transurethral resection (TUR) syndrome. METHODS: The records of patients who
underwent TUR of the prostate under regional anesthesia over a 6-year period were
retrospectively reviewed. TUR syndrome is usually defined as a serum sodium level
of < 125 mmol/l combined with clinical cardiovascular or neurological
manifestations. This study focused on the clinical manifestations only, and
recorded specific central nervous system and cardiovascular abnormalities
according to the checklist proposed by Hahn. Patients with and without clinical
manifestations of TUR syndrome were compared to determine the factors associated
with TUR syndrome. Receiver operating characteristic curve analysis was used to
determine the optimal cutoff value of estimated prostate weight for the
prediction of clinical manifestations of TUR syndrome. RESULTS: This study
included 167 patients, of which 42 developed clinical manifestations of TUR
syndrome. There were significant differences in preoperative estimated prostate
weight, operation time, resected prostate weight, intravenous fluid infusion
volume, blood transfusion volume, and drainage of the suprapubic irrigation fluid
between patients with and without clinical manifestations of TUR syndrome. The
preoperative estimated prostate weight was correlated with the resected prostate
weight (Spearman's correlation coefficient, 0.749). Receiver operator
characteristic curve analysis showed that the optimal cutoff value of estimated
prostate weight for the prediction of clinical manifestations of TUR syndrome was
75 g (sensitivity, 0.70; specificity, 0.69; area under the curve, 0.73).
CONCLUSIONS: Preoperative estimation of prostate weight by ultrasonography can
predict the development of clinical manifestations of TUR syndrome. Particular
care should be taken when the estimated prostate weight is > 75 g.
PMID- 25128189
TI - Physical and genetic interaction between ammonium transporters and the signaling
protein Rho1 in the plant pathogen Ustilago maydis.
AB - Dimorphic transitions between yeast-like and filamentous forms occur in many
fungi and are often associated with pathogenesis. One of the cues for such a
dimorphic switch is the availability of nutrients. Under conditions of nitrogen
limitation, fungal cells (such as those of Saccharomyces cerevisiae and Ustilago
maydis) switch from budding to pseudohyphal or filamentous growth. Ammonium
transporters (AMTs) are responsible for uptake and, in some cases, for sensing
the availability of ammonium, a preferred nitrogen source. Homodimer and/or
heterodimer formation may be required for regulating the activity of the AMTs. To
investigate the potential interactions of Ump1 and Ump2, the AMTs of the maize
pathogen U. maydis, we first used the split-ubiquitin system, followed by a
modified split-YFP (yellow fluorescent protein) system, to validate the
interactions in vivo. This analysis showed the formation of homo- and hetero
oligomers by Ump1 and Ump2. We also demonstrated the interaction of the high
affinity ammonium transporter, Ump2, with the Rho1 GTPase, a central protein in
signaling, with roles in controlling polarized growth. This is the first
demonstration in eukaryotes of the physical interaction in vivo of an ammonium
transporter with the signaling protein Rho1. Moreover, the Ump proteins interact
with Rho1 during the growth of cells in low ammonium concentrations, a condition
required for the expression of the Umps. Based on these results and the genetic
evidence for the interaction of Ump2 with both Rho1 and Rac1, another small
GTPase, we propose a model for the role of these interactions in controlling
filamentation, a fundamental aspect of development and pathogenesis in U. maydis.
PMID- 25128190
TI - Distribution and trends in outpatient utilization of generic versus brand name
psychopharmaceuticals during a ten-year period in Croatia.
AB - BACKGROUND: Drug costs increasingly pose a burden upon the otherwise inadequate
health care resources and rational drug utilization is an important segment of
every national health policy. Optimal patient care should be the goal of rational
pharmacotherapy, whereby the economic burden of treatment is just one of the
elements to be considered on choosing appropriate therapy.The aim of this study
was to determine distribution and trends in the outpatient utilization of generic
versus brand name psychopharmaceuticals and to evaluate the rationality of
prescribing psychopharmaceuticals during a ten-year period. METHODS: Using the
World Health Organization Anatomical-Therapeutic-Chemical classification/Defined
Daily Doses (ATC/DDD) methodology, the number of DDD was calculated from data
collected from pharmacies on the number and size of drug packages. The ratio of
generic and brand name drug costs served as an indicator on assessing the
rationality of drug utilization. RESULTS: Total cost for psychopharmaceuticals
increased by 20.1%, more for brand name than for generic agents (32.7% vs. 7.4%).
The highest share of generic psychopharmaceuticals as compared with brand name
drugs according to DDD per 1000 inhabitants per day (DDD/1000/day) was in the
group of psycholeptics (83.6% in 2001 vs. 82.2% in 2010), most in hypnotics and
sedatives, and least in antipsychotics. The share of generic
psychopharmaceuticals in total drug utilization according to financial indicators
decreased by 9.6% and according to DDD/1000/day by 12%. The greatest decrease was
in antidepressants, i.e. by 33.8% according to financial indicators and by 46%
according to DDD/1000/day; and in antipsychotics by 30.9% according to
DDD/1000/day, while showing an increase by 8.5% according to financial
indicators. In the therapeutic subgroup of mood stabilizers, the share of generic
drugs in total drug utilization declined by 32% according to DDD/1000/day, but
increased by 25.1% according to financial indicators. CONCLUSIONS: The lack of
uniform national guidelines and the still strong impact of pharmaceutical
industry marketing continue favoring the rise in prescribing brand name
antidepressants and antipsychotics. Depression, schizophrenia and bipolar
diseases are complex diseases. As a result, specific measures are needed to
encourage the prescribing of generic psychopharmaceuticals.
PMID- 25128191
TI - Receiver operating characteristic curve analysis to determine the diagnostic
performance of serum haptoglobin concentration for the diagnosis of acute
puerperal metritis in dairy cows.
AB - Acute puerperal metritis (APM) in dairy cows is characterized by fever and fetid
vaginal discharge within 21 days in milk (DIM). Increased serum haptoglobin
concentration (Hp) can support the diagnosis of APM. However, there is a dearth
of information of the test performance of Hp as a measure for APM with a
consistent definition and considering parity. The objective of this trial was to
study the test performance of Hp to distinguish healthy cows from cows with APM.
A total of 33 of 60 (55.0%) primiparous cows and 43 of 133 (32.3%) multiparous
cows developed APM. Primiparous cows with APM had the greatest Hp. However, in
primiparous cows Hp did not significantly differ between healthy cows (DIM 2:
1.49 +/- 0.64 mg/mL; DIM 5: 2.13 +/- 0.66 mg/mL; DIM 10: 1.46 +/- 0.85 mg/mL) and
cows with APM (DIM 2: 1.78 +/- 0.62 mg/mL; DIM 5: 2.48 +/- 0.64 mg/mL; DIM 10:
1.60 +/- 0.81 mg/mL). In multiparous cows, Hp was greater in cows with APM (DIM
2: 1.27 +/- 0.68 mg/mL; DIM 5: 1.89 +/- 0.94 mg/mL; DIM 10: 1.23 +/- 0.78 mg/mL)
than in healthy cows (DIM 2: 0.99 +/- 0.68 mg/mL; DIM 5: 1.10 +/- 0.80 mg/mL; DIM
10: 0.83 +/- 0.68 mg/mL). Sensitivity and specificity of Hp to diagnose APM in
multiparous cows ranged from 72% to 79% and 54% to 71% on DIM 2, 5 and 10,
respectively.
PMID- 25128192
TI - Novel approaches to target NF-kappaB and other signaling pathways in cancer stem
cells.
AB - Recently cancer tissue is considered to consist of large number of balk cancer
cells and a small number of cancer stem cells. After surgery, radiotherapy, or
chemotherapy, most cancer cells are removed, but if there are still very small
number of cancer stem cells left. They may form the similar tumor again. So
removal of cancer stem cells is considered to be important for future cancer
therapy. In one hand, NF-kappaB is the transcription factor that promotes
expressions of various inflammatory cytokines and apoptosis inhibitory proteins.
Cancer cells often possess constitutively activated NF-kappaB that often provides
excess survival and therapeutic resistance in cancer cells. We have discovered
DHMEQ as a specific inhibitor of NF-kappaB. This compound was found to be more
active in cancer stem cells than in balk cancer cells. In breast cancer cells
both PI3K-Akt and NF-kappaB pathways appear in the survival of cancer stem cells.
PMID- 25128193
TI - Vitamin D deficiency and lower TGF-beta/IL-17 ratio in a North Indian cohort of
pemphigus vulgaris.
AB - BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune bullous disease caused by
acantholysis of keratinocytes due to pathogenic desmoglein-3 autoantibodies. Role
of vitamin D has been recently implicated in various autoimmune conditions due to
its immunomodulatory effects on innate and adaptive immune responses. One of the
key mechanisms of the immune regulation by vitamin D is through its anti
inflammatory effects by suppression of Th17 functions. Thus, vitamin D may be
involved in pathogenesis of PV. In this study, the serum vitamin D, IL-17 and TGF
beta levels in PV patients as well as healthy controls were estimated in order to
understand the underlying immune mechanism involved in disease pathogenesis.
RESULTS: This retrospective study included 30 biopsy proven PV patients' sera.
Ten age matched volunteers without any cutaneous or autoimmune conditions were
recruited as healthy control (HC). Serum Vitamin D levels were measured using
chemiluminescence, whereas IL-17 and TGF-beta levels were determined using ELISA.
All patients showed deficient vitamin D levels (11.1 +/- 5.8 ng/ml). Moreover,
all the PV patients had elevated serum IL-17 levels (210.7 +/- 105.3), whereas it
was not detectable in any (n = 10) of the healthy controls sera (ELISA
sensitivity >= 8 pg/ml). The mean serum TGF-beta concentration was also lower in
patient sera as compared to healthy control, and the TGF-beta/IL-17 ratio was
drastically reduced in patients (30.30 +/- 28), as compared to healthy controls
(1363.34 +/- 559.52). CONCLUSIONS: Hypovitaminosis is common in North India, as
ascertained by deficient levels in healthy controls, and was also consistently
observed in PV patient. These low levels were not related to age or gender. The
increased serum IL-17 and dramatic reduction in TGF-beta/IL-17 ratio in diseased
patients further indicate that dysregulation of the Treg/Th-17 axis of T effector
cells may be of significance in pathogenesis of PV. Thus, the study indicates
that vitamin D insufficiency may be a predisposing factor in PV, contributing
through its role in any of the various adaptive immune mechanisms that regulate T
cell functions in vivo. Thus, there is a need to further evaluate the Treg/Th-17
axis, as it may have an important role in disease progression.
PMID- 25128194
TI - Morphisms of reaction networks that couple structure to function.
AB - BACKGROUND: The mechanisms underlying complex biological systems are routinely
represented as networks. Network kinetics is widely studied, and so is the
connection between network structure and behavior. However, similarity of
mechanism is better revealed by relationships between network structures.
RESULTS: We define morphisms (mappings) between reaction networks that establish
structural connections between them. Some morphisms imply kinetic similarity, and
yet their properties can be checked statically on the structure of the networks.
In particular we can determine statically that a complex network will emulate a
simpler network: it will reproduce its kinetics for all corresponding choices of
reaction rates and initial conditions. We use this property to relate the
kinetics of many common biological networks of different sizes, also relating
them to a fundamental population algorithm. CONCLUSIONS: Structural similarity
between reaction networks can be revealed by network morphisms, elucidating
mechanistic and functional aspects of complex networks in terms of simpler
networks.
PMID- 25128195
TI - Prokineticin 1 and leukemia inhibitory factor mRNA expression in the endometrium
of women with idiopathic recurrent pregnancy loss.
AB - OBJECTIVE: To determine the expression patterns of prokineticin 1 (PROK1) and
leukemia inhibitory factor (LIF) mRNA differ in peri-implantation endometrial
tissue of women with idiopathic recurrent pregnancy loss (RPL) from normal
fertile women. DESIGN: A case-control study. SETTING: University-based tertiary
care center. PATIENT(S): 30 women with idiopathic RPL and 30 fertile controls.
INTERVENTION(S): Endometrial biopsies. MAIN OUTCOME MEASURE(S): Real-time
polymerase chain reaction analysis for expression of PROK1 and LIF mRNA.
RESULT(S): The expression of PROK1 and LIF was statistically significantly
increased in the endometrium of the women with idiopathic RPL compared with the
controls. Furthermore, increased LIF expression was observed in the endometrium
of women with idiopathic RPL compared with controls. CONCLUSION(S): An increased
mRNA expression of PROK1 and LIF could be one of the several abnormalities
characterizing the endometrium in women with RPL.
PMID- 25128196
TI - BESST--efficient scaffolding of large fragmented assemblies.
AB - BACKGROUND: The use of short reads from High Throughput Sequencing (HTS)
techniques is now commonplace in de novo assembly. Yet, obtaining contiguous
assemblies from short reads is challenging, thus making scaffolding an important
step in the assembly pipeline. Different algorithms have been proposed but many
of them use the number of read pairs supporting a linking of two contigs as an
indicator of reliability. This reasoning is intuitive, but fails to account for
variation in link count due to contig features.We have also noted that published
scaffolders are only evaluated on small datasets using output from only one
assembler. Two issues arise from this. Firstly, some of the available tools are
not well suited for complex genomes. Secondly, these evaluations provide little
support for inferring a software's general performance. RESULTS: We propose a new
algorithm, implemented in a tool called BESST, which can scaffold genomes of all
sizes and complexities and was used to scaffold the genome of P. abies (20 Gbp).
We performed a comprehensive comparison of BESST against the most popular stand
alone scaffolders on a large variety of datasets. Our results confirm that some
of the popular scaffolders are not practical to run on complex datasets.
Furthermore, no single stand-alone scaffolder outperforms the others on all
datasets. However, BESST fares favorably to the other tested scaffolders on GAGE
datasets and, moreover, outperforms the other methods when library insert size
distribution is wide. CONCLUSION: We conclude from our results that information
sources other than the quantity of links, as is commonly used, can provide useful
information about genome structure when scaffolding.
PMID- 25128197
TI - Shaping zoonosis risk: landscape ecology vs. landscape attractiveness for people,
the case of tick-borne encephalitis in Sweden.
AB - BACKGROUND: In this paper, the hazard and exposure concepts from risk assessment
are applied in an innovative approach to understand zoonotic disease risk. Hazard
is here related to the landscape ecology determining where the hosts, vectors and
pathogens are and, exposure is defined as the attractiveness and accessibility to
hazardous areas. Tick-borne encephalitis in Sweden was used as a case study.
METHODS: Three boosted regression tree models are compared: a hazard model, an
exposure model and a global model which combines the two approaches. RESULTS: The
global model offers the best predictive power and the most accurate modelling.
The highest probabilities were found in easy-to-reach places with high landscape
diversity, holiday houses, waterbodies and, well-connected forests of oak, birch
or pine, with open-area in their ecotones, a complex shape, numerous clear-cuts
and, a variation in tree height. CONCLUSION: While conditions for access and use
of hazardous areas are quite specific to Scandinavia, this study offers promising
perspectives to improve our understanding of the distribution of zoonotic and
vector-borne diseases in diverse contexts.
PMID- 25128198
TI - Evaluation of anterior segment parameters during and after pregnancy.
AB - PURPOSE: To compare the anterior segment parameters during pregnancy and post
pregnancy. MATERIALS AND METHODS: Fifty-four healthy pregnant women in their
third trimester with ages ranging from 18 to 38 years were included in the study.
All of the patients underwent comprehensive ophthalmologic examinations,
including refraction, anterior segment, and fundus examinations, intraocular
pressure, and axial length measurements. In addition, anterior chamber angle,
anterior chamber depth, anterior chamber volume, corneal volume, central corneal
thickness, and keratometry values were measured by Pentacam Scheimpflug camera.
All measurements were measured again 3 months after delivery. RESULTS: The mean
intraocular pressure, anterior chamber angle, anterior chamber depth, anterior
chamber volume, corneal volume, central corneal thickness, and keratometry
measurements were significantly different during pregnancy and post-pregnancy
(p<0.05 for all); however, the mean spherical refraction, cylindrical refraction,
and axial length were not statistically significantly different during pregnancy
and post-pregnancy (p>0.05 for all). CONCLUSIONS: We found that there is an
increase in the anterior chamber parameters, corneal volume, corneal thickness,
and corneal curvature and a decrease in intraocular pressure in the third
trimester.
PMID- 25128199
TI - Tumour necrosis factor, interleukin-6 and interleukin-10 are possibly involved in
Plasmodium vivax-associated thrombocytopaenia in southern Pakistani population.
AB - BACKGROUND: In Pakistan, Plasmodium vivax is endemic causing approximately 70% of
the malaria cases. A number of haematological changes, especially
thrombocytopaenia have been reported for P. vivax. Several host factors including
cell-mediated immune cells, such as IL-1, IL-6 and IL-10 have been documented for
P. vivax-induced thrombocytopaenia. However, study on correlation of cytokines
and thrombocytopaenia in P. vivax, particularly in patients with severe signs and
symptoms has not been reported from Pakistan. METHODS: A case control study to
correlate TNF, IL-6 and IL-10 in healthy controls and thrombocytopaenic P. vivax
infected patients (both uncomplicated and complicated cases) from southern
Pakistan was carried out during January 2009 to December 2011. One Hundred and
eighty two patients presenting with microscopy-confirmed asexual P. vivax mono
infection and 100 healthy controls were enrolled in the study at Aga Khan
University Hospital, Karachi. Enzyme-linked immunosorbent assay (ELISA) was
performed for determination of TNF, IL-6 and IL-10 levels. RESULTS: Out of 182
cases, mild thrombocytopaenia (platelet count 100,000-150,000 mm3) was observed
in ten (5.5%), moderate (50,000-100,000 mm3) in 93 (51.1%), and profound
thrombocytopaenia (<50,000 mm3) was detected in 79 (43.4%) patients. IL-6 and IL
10 levels were found approximately three-fold higher in the mild cases compared
to healthy controls. Two-fold increase in TNF and IL-10 (p < 0.0001) was observed
in profound thrombocytopaenic when compared with moderate cases, while IL-6 was
not found to be significantly elevated. CONCLUSION: Cytokines may have a possible
role in P. vivax-induced thrombocytopaenia in Pakistani population. Findings from
this study give first insight from Pakistan on the role of cytokines in P.vivax
associated thrombocytopaenia. However, further studies are required to understand
the relevance of cytokines in manifestations of thrombocytopaenia in P. vivax
malaria.
PMID- 25128200
TI - Sequence analysis of porothramycin biosynthetic gene cluster.
AB - The biosynthetic gene cluster of porothramycin, a sequence-selective DNA
alkylating compound, was identified in the genome of producing strain
Streptomyces albus subsp. albus (ATCC 39897) and sequentially characterized. A
39.7 kb long DNA region contains 27 putative genes, 18 of them revealing high
similarity with homologous genes from biosynthetic gene cluster of closely
related pyrrolobenzodiazepine (PBD) compound anthramycin. However, considering
the structures of both compounds, the number of differences in the gene
composition of compared biosynthetic gene clusters was unexpectedly high,
indicating participation of alternative enzymes in biosynthesis of both
porothramycin precursors, anthranilate, and branched L-proline derivative. Based
on the sequence analysis of putative NRPS modules Por20 and Por21, we suppose
that in porothramycin biosynthesis, the methylation of anthranilate unit occurs
prior to the condensation reaction, while modifications of branched proline
derivative, oxidation, and dimethylation of the side chain occur on already
condensed PBD core. Corresponding two specific methyltransferase encoding genes
por26 and por25 were identified in the porothramycin gene cluster. Surprisingly,
also methyltransferase gene por18 homologous to orf19 from anthramycin
biosynthesis was detected in porothramycin gene cluster even though the
appropriate biosynthetic step is missing, as suggested by ultra high-performance
liquid chromatography-diode array detection-mass spectrometry (UHPLC-DAD-MS)
analysis of the product in the S. albus culture broth.
PMID- 25128201
TI - A cross-sectional analysis of the relationship between uric acid and coronary
atherosclerosis in patients with suspected coronary artery disease in China.
AB - BACKGROUND: Although many studies have examined the relationship between uric
acid (UA) and coronary artery disease (CAD), whether UA is an independent risk
factor contributing to progression of CAD is still controversial. Whether UA
plays a different role in different sexes is also unclear. METHODS: A total of
1116 individuals with suspected CAD were stratified into four groups according to
their serum UA quartiles in total (men and women combined), in men, and in women.
The association of UA with coronary atherosclerosis was assessed by univariable
and multivariable logistic regression. RESULTS: In total and in women, the
prevalence of any plaques and significant/severe stenosis was significantly
increased with an increase in quartiles of UA (all P < 0.05). The proportion of
triple-vessel disease and left main artery lesion was highest in the fourth
quartile (both p < 0.05). Increasing quartiles of UA were significantly
associated with a coronary artery calcium score (CACS) >10 (all P < 0.01). As UA
levels increased in women, the incidence of double-vessel lesions (p = 0.017) and
the proportion of mixed plaques (p = 0.022) were significantly increased. The
proportion of a CACS of 0 in total, in men and women was highest in the first
quartile (all P < 0.01). UA was the strongest predictor of significant stenosis,
multivessel disease, and mixed plaques in women (all p < 0.05). UA was the only
risk factor for mixed plaques in total (P = 0.046). CONCLUSION: The level of UA
was significantly associated with coronary atherosclerosis in women, but not men.
PMID- 25128202
TI - The radiosensitising effect of gemcitabine and its main metabolite dFdU under low
oxygen conditions is in vitro not dependent on functional HIF-1 protein.
AB - BACKGROUND: Regions within solid tumours often experience oxygen deprivation,
which is associated with resistance to chemotherapy and irradiation. The aim of
this study was to evaluate the radiosensitising effect of gemcitabine and its
main metabolite dFdU under normoxia versus hypoxia and to determine whether
hypoxia-inducible factor 1 (HIF-1) is involved in the radiosensitising mechanism.
METHODS: Stable expression of dominant negative HIF-1alpha (dnHIF) in MDA-MB-231
breast cancer cells, that ablated endogenous HIF-1 transcriptional activity, was
validated by western blot and functionality was assessed by HIF-1alpha activity
assay. Cells were exposed to varying oxygen environments and treated with
gemcitabine or dFdU for 24 h, followed by irradiation. Clonogenicity was then
assessed. Using radiosensitising conditions, cells were collected for cell cycle
analysis. RESULTS: HIF-1 activity was significantly inhibited in cells stably
expressing dnHIF. A clear radiosensitising effect under normoxia and hypoxia was
observed for both gemcitabine and dFdU. No significant difference in
radiobiological parameters between HIF-1 proficient and HIF-1 deficient MDA-MB
231 cells was demonstrated. CONCLUSIONS: For the first time, radiosensitisation
by dFdU, the main metabolite of gemcitabine, was demonstrated under low oxygen
conditions. No major role for functional HIF-1 protein in radiosensitisation by
gemcitabine or dFdU could be shown.
PMID- 25128204
TI - Identifying factors of bicycle comfort: An online survey with enthusiast
cyclists.
AB - Racing bicycles have evolved significantly over the past decades as technology
and cyclists' comfort have become a critical design issue. Although ample
research has been conducted on comfort for other means of transportation,
cyclists' perception of dynamic comfort has received scant attention in the
scientific literature. The present study investigates how enthusiast cyclists
conceptualize comfort using an online survey with 244 respondents. The purpose is
to determine which factors contribute to comfort when riding a bicycle, to
identify situations in which comfort is relevant and to determine the extent to
which vibrations play a role in comfort evaluations. We found that comfort is
influenced by factors related to bicycle components (specifically the frame,
saddle and handlebar), as well as environmental factors (type or road, weather
conditions) and factors related to the cyclist (position, adjustments, body
parts). Respondents indicated that comfort is a concern when riding a bicycle in
most situations and they believed that comfort is compatible with performance.
The PCA analysis shows that for the perception "human factor-body parts" are put
in evidence, and the "cyclist's comfort" evaluation is mainly based on certain
qualities related to the bicycle components, then the road and external
conditions (e.g. weather, temperature).
PMID- 25128203
TI - Strength training reduces circulating interleukin-6 but not brain-derived
neurotrophic factor in community-dwelling elderly individuals.
AB - Ageing is associated with a chronic low-grade inflammatory profile (CLIP).
Physical exercise could circumvent the deleterious effects of CLIP by influencing
circulating inflammatory mediators and neurotrophic growth factors. This study
aimed at assessing whether 12 weeks of progressive strength training (PST)
influences circulating brain-derived neurotrophic factor (BDNF), interleukin (IL)
6 and IL-10 in elderly individuals. Forty community-dwelling persons aged 62-72
years participated. Twenty participants were assigned to 12-week PST (70-80 % of
maximal strength, three times per week). Matched control individuals (n = 20)
maintained daily activity levels. Serum was collected for BDNF, IL-6 and IL-10
assay from all participants before and after 12 weeks (for PST subjects 24-48 h
after the last training). In PST, muscle strength was significantly improved (+49
% for leg extension, p = 0.039), and basal IL-6 levels significantly reduced (p =
0.001), which remained unchanged in control (p = 0.117). No significant change in
BDNF was observed in PST subjects (p = 0.147) or control (p = 0.563). IL-10 was
below the detection limit in most subjects. Gender and health status did not
influence the results. Our results show that after 12-week PST, muscle
performance improved significantly, and basal levels of IL-6 were significantly
decreased in older subjects. However, serum BDNF was not altered. The lack of an
observable change in BDNF might be due to a short-lived BDNF response, occurring
acutely following exercise, which might have been washed out when sampling.
Furthermore, blood levels of BDNF may not reflect parallel increases that occur
locally in the brain and muscle. These hypotheses need confirmation by further
studies.
PMID- 25128205
TI - The WERCAP Screen and the WERC Stress Screen: psychometrics of self-rated
instruments for assessing bipolar and psychotic disorder risk and perceived
stress burden.
AB - BACKGROUND: Identification of individuals in the prodromal phase of bipolar
disorder and schizophrenia facilitates early intervention and promises an
improved prognosis. There are no current assessment tools for clinical risk
symptoms of bipolar disorder, and psychosis-risk assessment generally involves
semi-structured interviews, which are time consuming and rater dependent. We
present psychometric data on two novel quantitative questionnaires: the
Washington Early Recognition Center Affectivity and Psychosis (WERCAP) Screen for
assessing bipolar and psychotic disorder risk traits, and the accompanying WERC
Stress Screen for assessing individual and total psychosocial stressor
severities. METHODS: Prevalence rates of the WERCAP Screen were evaluated among
171 community youth (aged 13-24 years); internal consistency was assessed and k
means cluster analysis was used to identify symptom groups. In 33 participants,
test-retest reliability coefficients were assessed, and ROC curve analysis was
used to determine the validity of the psychosis section of the WERCAP Screen
(pWERCAP) against the Structured Interview of Psychosis-Risk Symptoms (SIPS).
Correlations of the pWERCAP, the affectivity section of the WERCAP Screen
(aWERCAP) and the WERC Stress Screen were examined to determine the relatedness
of scores with cognition and clinical measures. RESULTS: Cluster analysis
identified three groups of participants: a normative (47%), a psychosis
affectivity (18%) and an affectivity only (35%) group. Internal consistency of
the aWERCAP and pWERCAP resulted in alphas of 0.87 and 0.92, and test-retest
reliabilities resulted in intraclass correlation coefficients of 0.76 and 0.86
respectively. ROC curve analysis showed the optimal cut-point on the pWERCAP as a
score of >30 (sensitivity: 0.89; specificity: 1.0). There was a significant
negative correlation between aWERCAP scores and total cognition (R=-0.42), and
between pWERCAP scores and sensorimotor processing speed. Total stress scores
correlated significantly with scores on the aWERCAP (R=0.88), pWERCAP (R=0.62)
and total cognition (R=-0.44). CONCLUSIONS: Our results show that the WERCAP
Screen and the WERC Stress Screen are easy to administer and derived scores are
related to cognitive and clinical traits. This suggests that their use could have
particular benefits for epidemiologic studies and in busy clinical settings.
Longitudinal studies would be required to evaluate clinical outcomes with high
questionnaire scores.
PMID- 25128206
TI - The reliability of biomechanical variables collected during single leg squat and
landing tasks.
AB - INTRODUCTION: The aim of this study was to determine the within- and between-day
reliability of lower limb biomechanical variables collected during single leg
squat (SLS) and single leg landing (SLL) tasks. METHODS: 15 recreational athletes
took part in three testing sessions, two sessions on the same day and another
session one week later. Kinematic and kinetic data was gathered using a ten
camera movement analysis system (Qualisys) and a force platform (AMTI) embedded
into the floor. RESULTS: The combined averages of within-day ICC values
(ICCSLS=0.87; ICCSLL=0.90) were higher than between-days (ICCSLS=0.81;
ICCSLL=0.78). Vertical GRF values (ICCSLS=0.90; ICCSLL=0.98) were more reliable
than joint angles (ICCSLS=0.85; ICCSLL=0.82) and moments (ICCSLS=0.83;
ICCSLL=0.87). DISCUSSION: This study demonstrates that all joint angles, moments,
and vertical ground reaction force (GRF) variables obtained during both tasks
showed good to excellent consistency with relatively low standard error of
measurement values. These findings would be of relevance to practitioners who are
using such measures for screening and prospective studies of rehabilitative
techniques.
PMID- 25128208
TI - Item-properties may influence item-item associations in serial recall.
AB - Attributes of words, such as frequency and imageability, can influence memory for
order. In serial recall, Hulme, Stuart, Brown, and Morin (Journal of Memory and
Language, 49(4), 500-518, 2003) found that high-frequency words were recalled
worse, and low-frequency words better, when embedded in alternating lists than
pure lists. This is predicted by associative chaining, wherein each recalled list
item becomes a recall-cue for the next item. However, Hulme, Stuart, Brown, and
Morin (Journal of Memory and Language, 49(4), 500-518, 2003) argued their
findings supported positional-coding models, wherein items are linked to a
representation of position, with no direct associations between items. They
suggested their serial-position effects were due to pre-experimental semantic
similarity between pairs of items, which depended on frequency, or a complex
tradeoff between item- and order-coding (Morin, Poirier, Fortin, & Hulme,
Psychonomic Bulletin Review, 13(4), 724-729, 2006). We replicated the smooth
serial-position effects, but accounts based on pre-existing similarity or item
order tradeoffs were untenable. Alternative accounts based, on imageability,
phonological and lexical neighbourhood sizes were also ruled out. The standard
chaining account predicts that if accuracy is conditionalized on whether the
prior item was correct, the word-frequency effect should reappear in alternating
lists; however, this prediction was not borne out, challenging this retrieval
based chaining account. We describe a new account, whereby frequency influences
the strengths of item-item associations, symmetrically, during study. A
manipulation of word-imageability also produced a pattern consistent with item
item cueing at study, but left room for effects of imageability at the final
stage of recall. These findings provide further support for the contribution of
associative chaining to serial-recall behaviour and show that item-properties may
influence serial-recall in multiple ways.
PMID- 25128209
TI - Effects of difficulty, specificity, and variability on training to follow
navigation instructions.
AB - To study the relative merits of three training principles - difficulty of
training, specificity of training, and variability of training - subjects were
trained to follow navigation instructions to move in a grid on a computer screen.
Subjects repeated and then followed the instructions by mouse clicking on the
grid. They were trained, given a short distractor task, and then tested. There
were three groups, each receiving different message lengths during training: easy
(short lengths), hard (long lengths), and mixed (all lengths), with all subjects
given all lengths at test. At test, the mixed group was best on most lengths, the
easy group was better than the hard group on short lengths, and the hard group
was better than the easy group on long lengths. The results support the
advantages of both specificity and variability of training but do not support the
hypothesis that difficult training of the form used here would lead to overall
best performance at test.
PMID- 25128210
TI - Evaluating the cost-effectiveness of preventive zinc supplementation.
AB - BACKGROUND: Even though the WHO currently recommends zinc for diarrhea
management, no consensus has been reached with respect to routine distribution of
zinc for preventive reasons. We reviewed the health impact of preventive zinc
interventions, and evaluated the relative cost effectiveness of currently
feasible interventions. METHODS: Using the latest relative risk estimates
reported in the literature, we parameterized a health impact model, and
calculated the expected benefits of zinc supplementation in a representative low
income country. We then computed the cost and cost-effectiveness for three
delivery mechanisms: the direct distribution of zinc supplements, the
distribution of micronutrient biscuits including zinc, and the distribution of
zinc through water filtration systems. RESULTS: Combining all health outcomes and
impact estimates, we find that systematic zinc supplementation among children of
ages one to five would avert 1.423 DALYs per 100 households and year in least
developed countries. The estimated cost per DALY is US$ 606 for pill
supplementation, US$ 1211 for micronutrient biscuits, and US$ 879 per DALY saved
for water filtration systems. CONCLUSIONS: Preventive zinc supplementation to
children of ages 1-5 appears to be a highly cost-effective intervention in
typical developing country settings. More research will be needed to determine
the most effective mechanism to deliver zinc to this target population.
PMID- 25128211
TI - Evaluation of the impact of a school gardening intervention on children's fruit
and vegetable intake: a randomised controlled trial.
AB - BACKGROUND: Current academic literature suggests that school gardening programmes
can provide an interactive environment with the potential to change children's
fruit and vegetable intake. This is the first cluster randomised controlled trial
(RCT) designed to evaluate whether a school gardening programme can have an
effect on children's fruit and vegetable intake. METHODS: The trial included
children from 23 schools; these schools were randomised into two groups, one to
receive the Royal Horticultural Society (RHS)-led intervention and the other to
receive the less involved Teacher-led intervention. A 24-hour food diary (CADET)
was used to collect baseline and follow-up dietary intake 18 months apart.
Questionnaires were also administered to evaluate the intervention
implementation. RESULTS: A total of 641 children completed the trial with a mean
age of 8.1 years (95% CI: 8.0, 8.4). The unadjusted results from multilevel
regression analysis revealed that for combined daily fruit and vegetable intake
the Teacher-led group had a higher daily mean change of 8 g (95% CI: -19, 36)
compared to the RHS-led group -32 g (95% CI: -60, -3). However, after adjusting
for possible confounders this difference was not significant (intervention
effect: -40 g, 95% CI: -88, 1; p = 0.06). The adjusted analysis of process
measures identified that if schools improved their gardening score by 3 levels (a
measure of school gardening involvement - the scale has 6 levels from 0 'no
garden' to 5 'community involvement'), irrespective of group allocation, children
had, on average, a daily increase of 81 g of fruit and vegetable intake (95% CI:
0, 163; p = 0.05) compared to schools that had no change in gardening score.
CONCLUSIONS: This study is the first cluster randomised controlled trial designed
to evaluate a school gardening intervention. The results have found very little
evidence to support the claims that school gardening alone can improve children's
daily fruit and vegetable intake. However, when a gardening intervention is
implemented at a high level within the school it may improve children's daily
fruit and vegetable intake by a portion. Improving children's fruit and vegetable
intake remains a challenging task. TRIAL REGISTRATION: ISRCTN11396528.
PMID- 25128212
TI - Guidelines for the diagnosis and treatment of adrenal insufficiency in the adult.
AB - Adrenal insufficiency (AI) is a disease characterized by a deficient production
or action of glucocorticoids, with or without deficiency in mineral corticoids
and/or adrenal androgens. It can result from disease intrinsic to the adrenal
cortex (primary AI), from pituitary diseases that hamper the release of
corticotropin (secondary AI) or from hypothalamic disorders that impair the
secretion of the corticotropin-releasing hormone (tertiary AI). It is a disease
with a low prevalence but its impact on the affected individual is very high as
it can be life-threathening if not treated or lead to health problems if
inadequately treated. However, currently there are no specific guidelines for the
management of this disease. Therefore, at the proposal of the Spanish Society of
Endocrinology and Nutrition (SEEN) board, a task-force under the
Neuroendocrinology Knowledge Area of the SEEN was established, with the mandate
of updating the diagnosis and treatment of AI. In fulfilment of this mandate the
task-force has elaborated the present guide that, based on a comprehensive review
of literature, is intended to provide an answer to questions related to the
management of this disease. It is, therefore, an essentially practical document,
mainly aimed at guiding the health professionals involved in the care of IA
patients.
PMID- 25128213
TI - Is there still a role for bilobed/bipaddled pectoralis major myocutaneous flap
for single-stage immediate reconstruction of post ablative oncologic full
thickness defects of the cheek?
AB - INTRODUCTION: Reconstruction of full-thickness defects of the head and neck is a
challenge. In this clinical study, we assessed the role of the bilobed/bipaddled
pectoralis major myocutaneous flap (PMMF) for the reconstruction of large full
thickness defects of the cheek, after resection of oral cancer. MATERIALS AND
METHOD: After resection of oral cancer, 62 cases of through-and-through defects
of the oral cavity were reconstructed using folded/bipaddled/bilobed PMMF flap.
All were males and presented with locally advanced oral squamous cell carcinoma
(SCC), which involved the buccal mucosa and gingivo buccal sulcus (n = 53) and
gingivo buccal sulcus + lip (n = 9). RESULTS: All the flaps survived, and no
patient developed a major complication. The most common complication in the
current series was wound dehiscence. In 8% of cases, wound dehiscence was found
at the donor site; in 6.45% of cases, dehiscence was present at the recipient
site; and in 4.83% of cases, dehiscence was present at the neck. All the wounds
healed secondarily with regular dressings. CONCLUSION: The bilobed/bipaddled PMMF
is a straightforward and reliable flap that provides an effective mechanism to
reconstruct full-thickness cheek defects while avoiding the complexity of
microvascular free flaps. The bilobed/bipaddled PMMF has become our preferred
reconstruction option for large full-thickness defects after resection of oral
carcinoma.
PMID- 25128214
TI - Fluoroscopic findings post-peroral esophageal myotomy.
AB - Natural orifice transluminal endoscopic surgery (NOTES) is a surgical technique
that has been evolving rapidly. Endoscopic submucosal dissection was initiated in
1999, in Japan, for en-bloc resection of large lesions of the stomach (Zhou et
al., World J Gastroenterol 19:6962-6968, 2013, ; Kobara et al., Clin Exp
Gastroenterol 7:67-74, 2014). Since then, many additional therapies utilizing
natural transluminal endoscopic approach have evolved. Peroral endoscopic myotomy
(POEM) is a minimally invasive type of transluminal endoscopic surgery that was
recently developed for the treatment of achalasia and esophageal motility
disorders. The peroral endoscopic myotomy is a less invasive surgical treatment
that is suitable for all types of achalasia and used as an alternate to the
Heller myotomy. The radiographic findings of achalasia and surgical changes after
Heller myotomy have been described, however, very little is available on the post
POEM esophagram appearance. The purpose of this article is to illustrate the
anatomy, surgical procedure, and normal and abnormal findings seen on esophagrams
in patients who have undergone a POEM.
PMID- 25128215
TI - Pediatric sialadenitis.
AB - Sialadenitis in the pediatric population accounts for up to 10% of all salivary
gland disease. Viral parotitis and juvenile recurrent parotitis are the two most
common causes. Multiple factors, independently or in combination, can result in
acute, chronic, or recurrent acute salivary gland inflammation. Sialendoscopy has
emerged as the leading diagnostic technique and intervention for pediatric
sialadenitis. Sialendoscopy is a safe and effective gland-preserving treatment of
pediatric sialadenitis. Investigational studies are needed to address the impact
of steroid instillation, postoperative stenting, and long-term outcomes of
pediatric sialendoscopy. This article presents a comprehensive review of
pathophysiology, clinical presentation, diagnosis, and treatment of pediatric
sialadenitis.
PMID- 25128216
TI - ABT-724 alleviated hyperactivity and spatial learning impairment in the
spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder.
AB - Dysfunction of dopamine D4 receptor (D4R) is linked to attention
deficit/hyperactivity disorder (ADHD) as well as ADHD associated cognitive
impairment. Here, we tested the possible therapeutic benefit of the D4R-selective
agonist ABT-724 in adolescent spontaneously hypertensive rats (SHRs). ABT-724
treated SHRs were administered ABT-724 (0.04mg/kg, 0.16mg/kg or 0.64mg/kg) from
postnatal day (P) 28 to P32. Control SHRs and Sprague-Dawley (SD) rats were
injected with saline. Then two cohorts of rats were tested in the open field and
Lat maze that measured locomotion and non-selective attention (NSA),
respectively. Another cohort of rats was subjected to water maze task for
evaluation of spatial learning and memory. We found that control SHRs displayed
hyperactivity as well as impaired NSA and spatial learning compared with
normotensive SD rats. ABT-724 (0.16 and 0.64mg/kg) treatment alleviated
hyperactivity and spatial learning impairment in SHRs. No dose of ABT-724 tested
altered NSA in SHRs. Our results raise the possibility that ABT-724 may be used
as a therapeutic intervention for ADHD patients during adolescence.
PMID- 25128217
TI - Trigemino-cervical reflex in spinal cord injury.
AB - Abnormal enhancement of polysynaptic brainstem reflexes has been previously
reported in patients with spinal cord injury (SCI). We aimed to investigate
trigemino-cervical reflex (TCR) in SCI since it may reflect alterations in the
connections of trigeminal proprioceptive system and cervical motoneurons.
Consecutive 14 patients with SCI and 16 healthy subjects were included in this
study. All patients were in the chronic phase. TCR was recorded over
sternocleidomastoid (SCM) and splenius capitis (SC) muscles by stimulation of
infraorbital nerve. We measured onset latency, amplitudes and durations of
responses and compared between groups. We obtained stable responses over both
muscles after one sided stimulation in healthy volunteers whereas probability of
TCR was decreased in patients over both SCM (78.6% vs. 100%, p=0.050) and SC
(71.4% vs. 100%, p=0.022). The absence of TCR was related to use of oral baclofen
(>=50mg/day). However, when present, responses of SCI group had higher amplitudes
and were more persistent. We demonstrated that TCR probability was similar to
healthy subjects in SCI patients who used no or low dose oral baclofen. But it
had higher amplitudes and longer durations. It was not obtained in only two
patients who used oral baclofen more than 50mg/day.
PMID- 25128218
TI - Morphine and oxycodone, but not fentanyl, exhibit antinociceptive effects
mediated by G-protein inwardly rectifying potassium (GIRK) channels in an
oxaliplatin-induced neuropathy rat model.
AB - It has begun to be understood that MU-opioid receptor (MOR) produces ligand
biased agonism, which contributes to differential physiological functions of MOR
agonists. We previously demonstrated that in oxaliplatin-induced neuropathy in
rats, morphine and oxycodone exhibited antinociceptive effects while
antinociception of fentanyl was partial, and such different efficacies might
result from the different level of Gi/o protein activation. Based on our
background, to reveal further mechanism, we focused on the role of Gi/o protein
related downstream signaling, the G-protein inwardly rectifying K(+)1 (GIRK1)
channel. The GIRK1 channel blocker tertiapin-Q (30pmol) was
intracerebroventricularly (i.c.v.) or intrathecally (i.t.) administered to rats
with oxaliplatin-induced neuropathy. The antinociception of systemic morphine
(3mg/kg, subcutaneously (s.c.)) was suppressed only by pretreatment of i.t.
tertiapin-Q, while supraspinal tertiapin-Q suppressed only the antinociception of
systemic oxycodone (0.56mg/kg, s.c.). Partial antinocicpetion of fentanyl
(0.017mg/kg, s.c.) was neither affected by i.c.v nor i.t. tertiapin-Q. These
results demonstrated that GIRK1 channels differentially contribute to
antinociceptive effects of MOR agonists, and that action site of GIRK1 channels
is also different between morphine and oxycodone in oxaliplatin model. This study
suggests the possibility that GIRK1 channels have a crucial role for
antinociception of MOR agonists in oxaliplatin-induced neuropathy.
PMID- 25128219
TI - Neural activity analysis of pure chito-oligomer components separated from a
mixture of chitooligosaccharides.
AB - Chitooligosaccharides (COSs) are obtained from the in vivo and in vitro
degradation of chitosan, which is a natural biomaterial used successfully for
peripheral nerve repair. Also, COSs have been reported to be beneficial for the
nervous system and especially able to promote peripheral nerve regeneration. To
determine which component in a mixture of COSs was really responsible for the
neurotrophic action of COSs, this study was performed to separate the active
components of COSs and compare the neural activity of different pure components.
Hydrophilic interaction liquid chromatography (HILIC) was used to separate 5
chito-oligomers with single degrees of polymerization (DPs) from a mixture of
COSs. They were chitobiose, chitotriose, chitotetraose, chitopentaose, and
chitohexaose with DPs of 2-6, respectively. MTT assay indicated that chitotriose
induced the greatest increase in Schwann cell survival among 5 chito-oligomers.
Immunocytochemistry with anti-NF-200 showed that chitotriose significantly
encouraged neurite outgrowth from dorsal root ganglion (DRG) explants with the
greatest effect among 5 chito-oligomers. Our results suggest that chitotriose may
be a key component in COSs mixture.
PMID- 25128220
TI - In-flight rupture of breast implant pocket.
PMID- 25128221
TI - Blepharoplasty techniques in the management of orbito-temporal neurofibromatosis.
AB - We aimed to present blepharoplasty techniques we used for severe orbito-temporal
neurofibromatosis (NF). A retrospective noncomparative single-center case study
was undertaken on patients with orbito-temporal NF. Twenty-two patients with
orbito-temporal NF treated at the Department of Ophthalmology of Shanghai Ninth
People's Hospital between 2007 and 2011 participated in the study. They underwent
a standard ophthalmologic assessment for orbito-temporal NF involving both the
orbito-temporal soft tissue and bony orbits. The orbits were examined with three
dimensional computed tomography (CT) and all 22 patients underwent tumor
debulking, blepharoplasty, and orbital reconstruction. We modified the
conventional procedures. Our reconstructive techniques included eyelid reduction;
lateral canthal reattachment; for patients with collapse of the lateral orbital
margin, reconstruction of the orbital margin to be performed before reattaching
the lateral canthus to the implanted titanium mesh; anterior levator resection;
and frontalis suspension according to preoperative levator muscle function.
Visual acuity, tumor recurrence, and postoperative palpebral fissure and orbital
appearance were evaluated to assess outcomes. Acceptable cosmetic results were
obtained in 22 patients after debulking of the orbito-temporal NF and surgical
reconstruction. There was no loss of vision or visual impairment postoperatively.
All patients did not display recrudescence after a follow-up period of >1 year.
Three patients with residual ptosis were successfully treated with a second
ptosis repair. We believe that the blepharoplasty techniques described in the
treatment of orbito-palpebral NF may provide both functional and esthetic
benefits.
PMID- 25128222
TI - The effect of deployment to a combat zone on testosterone levels and the
association with the development of posttraumatic stress symptoms: A longitudinal
prospective Dutch military cohort study.
AB - OBJECTIVE: There is limited evidence on the association of the activity of HPG
axis with stress and symptoms of stress-related disorders. The aim of the current
study was to assess the effect of deployment to a combat zone on plasma
testosterone levels, and the possible association with the development of
symptoms of posttraumatic stress disorder (PTSD). METHODS: A total of 918 males
were included in the study before deployment to a combat zone in Afghanistan. The
effect of deployment on testosterone was longitudinally assessed; starting prior
to deployment and follow-up assessments were preformed at 1 and 6 months after
return. Furthermore, the association with PTSD symptoms reported at 1 and 2 years
post-deployment was assessed. RESULTS: Plasma testosterone levels were
significantly increased after deployment compared with pre-deployment levels.
Although no difference was found between individuals reporting high or low levels
of PTSD symptoms, pre-deployment testosterone levels predicted the development of
PTSD symptoms at 1 and 2 years post-deployment. CONCLUSION: This study provides
evidence that not the alterations in testosterone levels shortly after
deployment, but the pre-deployment testosterone levels are associated with PTSD
symptoms, which is of value in the identification of biological vulnerability
factors for the development of PTSD.
PMID- 25128223
TI - Growth, bone health, and later outcomes in infants born preterm.
PMID- 25128224
TI - Taking care of the caretakers to enhance antiretroviral adherence in HIV-infected
children and adolescents.
PMID- 25128225
TI - The relationships between insomnia, sleep apnoea and depression: findings from
the American National Health and Nutrition Examination Survey, 2005-2008.
AB - OBJECTIVE: To determine the association between insomnia, obstructive sleep
apnoea (OSA), and comorbid insomnia-OSA and depression, while controlling for
relevant lifestyle and health factors, among a large population-based sample of
US adults. METHOD: We examined a sample of 11,329 adults (>=18 years) who
participated in the National Health and Nutrition Examination Survey (NHANES)
during the years 2005-2008. Insomnia was classified via a combination of self
reported positive physician diagnosis and high-frequency 'trouble falling
asleep', 'waking during the night', 'waking too early', and 'feeling unrested
during the day'. OSA was classified as a combination of a positive response to a
physician-diagnosed condition, in addition to a high frequency of self-reported
nocturnal 'snoring', 'snorting/stopping breathing' and 'feeling overly sleepy
during the day'. Comorbid insomnia-OSA was further assessed by combining a
positive response to either insomnia (all), or sleep apnoea (all), as classified
above. Depressive symptomology was assessed by the Patient Health Questionnaire-9
(PHQ-9), with scores of >9 used to indicate depression. Odds ratios (ORs) and 95%
confidence intervals (CIs) for sleep disorders and depression were attained from
logistic regression modelling adjusted for sex, age, poverty level, smoking
status and body mass index (BMI). RESULTS: Those who reported insomnia, OSA or
comorbid insomnia-OSA symptoms reported higher rates of depression (33.6%, 22.2%,
27.1%, respectively), and consistently reported poorer physical health outcomes
than those who did not report sleep disorders. After adjusting for sex, age,
poverty level, smoking status and BMI (kg/m(2)), insomnia (OR 6.57, 95% CI 3.89
11.11), OSA (OR 5.14, 95% CI 3.14-8.41) and comorbid insomnia-OSA (OR 6.67, 95%
CI 4.44-10.00) were associated with an increased likelihood of reporting
depression. CONCLUSIONS: Insomnia, OSA and comorbid insomnia-OSA are associated
with significant depressive symptomology among this large population-based sample
of adults.
PMID- 25128226
TI - Progress towards parity: improving the physical health of long-term psychiatric
inpatients.
PMID- 25128227
TI - Identification of putative pathogenic microRNA and its downstream targets in
anaplastic lymphoma kinase-negative anaplastic large cell lymphoma.
AB - Anaplastic large cell lymphomas (ALCL) are tumors of T/null-cell lineage
characterized by uniform CD30 expression. The 2008 World Health Organization
classification subdivided ALCLs into 2 groups: anaplastic lymphoma kinase (ALK)
positive (established entity) and ALK-negative (proposed new entity) ALCL. The
genetic basis for the pathogenesis of newly categorized ALK- ALCL is poorly
understood. In this study, we used microRNA microarray analysis to identify
differentially expressed microRNAs in ALK+ and ALK- ALCL. ALK- ALCL showed
significantly higher expression of miR-155 (0.888 +/- 0.228) compared with ALK+
ALCL (0.0565 +/- 0.009) on microarray and by quantitative real-time polymerase
chain reaction in ALK- ALCL compared with ALK+ ALCL (P < .05) with a strong
correlation between the 2 platforms (R = 0.9, P < .0003). A novel in situ
hybridization method allows direct visualization of expression patterns and
relative quantitation of miR-155 (mean score, 2.3 versus 1.3; P = .01) for the
first time in tissue sections of ALCL. Among computationally predicted targets of
miR-155, we identified ZNF652 (r = -0.57, P = .05), BACH1 (r = 0.88, P = .02),
RBAK (r = 0.81, P = .05), TRIM32 (r = 0.92, P = .01), E2F2 (r = 0.81, P = .05),
and TP53INP1 (r = -0.31, P = .03) as genes whose expression by quantitative real
time polymerase chain reaction correlated significantly with the level of miR-155
in ALCL tumor tissue.
PMID- 25128229
TI - Diagnosis of major cancer resection specimens with virtual slides: impact of a
novel digital pathology workstation.
AB - Digital pathology promises a number of benefits in efficiency in surgical
pathology, yet the longer time required to review a virtual slide than a glass
slide currently represents a significant barrier to the routine use of digital
pathology. We aimed to create a novel workstation that enables pathologists to
view a case as quickly as on the conventional microscope. The Leeds Virtual
Microscope (LVM) was evaluated using a mixed factorial experimental design.
Twelve consultant pathologists took part, each viewing one long cancer case (12
25 slides) on the LVM and one on a conventional microscope. Total time taken and
diagnostic confidence were similar for the microscope and LVM, as was the mean
slide viewing time. On the LVM, participants spent a significantly greater
proportion of the total task time viewing slides and revisited slides more often.
The unique design of the LVM, enabling real-time rendering of virtual slides
while providing users with a quick and intuitive way to navigate within and
between slides, makes use of digital pathology in routine practice a realistic
possibility. With further practice with the system, diagnostic efficiency on the
LVM is likely to increase yet more.
PMID- 25128228
TI - Prostate cancer with Paneth cell-like neuroendocrine differentiation has
recognizable histomorphology and harbors AURKA gene amplification.
AB - Aurora kinase A (AURKA) gene amplification has been documented in 67% of hormone
naive prostate cancer cases that progress to a highly aggressive variant of
castrate-resistant disease, clinically referred to as "neuroendocrine" prostate
cancer, "small cell" prostate carcinoma, or "anaplastic" prostate cancer.
Therefore, AURKA amplification is a potential prognostic biomarker that may help
to identify patients with prostate cancer who are at high risk for developing
castrate-resistant disease with clinical features of small cell carcinoma.
Furthermore, AURKA inhibitors are currently being tested in clinical trials. In a
previous study, we found AURKA amplification in 6 cases of prostate cancer with
Paneth cell-like cells. This morphologic pattern has been suggested to represent
low-grade neuroendocrine differentiation (NED) with generally favorable
prognosis. We sought to investigate the frequency of AURKA amplification and the
histologic characteristics of prostate cancer with Paneth cell-like NED. Twenty
five cases from 172 prostatectomies were evaluated for the presence of 18
morphologic features and AURKA amplification. Most prostate cancers with Paneth
cell-like NED had macronucleoli (92%), basophilic appearance (88%), perineural
invasion (72%), and nuclear stratification (76%). The frequency of AURKA
amplification was 45%, present throughout the examined tumor nodule including
areas without Paneth cell-like cells. When histologically similar cases with and
without AURKA amplification were compared, this gene alteration was associated
with larger extent of Paneth cell-like NED identified at magnification *20 (P =
.015), higher percentage of Paneth cell-like NED throughout the tumor nodule (P =
.033), ductal features (P = .02), and higher overall Gleason grade (P = .039).
AURKA amplification was not associated with age, serum prostate specific antigen,
or tumor stage. The high frequency of AURKA amplification (45%) in localized
prostate cancer with Paneth cell-like NED and its potential prognostic
significance warrant further investigation.
PMID- 25128230
TI - How neuronal computations depend on network state: another piece in the puzzle.
PMID- 25128231
TI - Dissecting mechanisms behind force control in humans by a mixture of
experimentation, mathematical analysis and computer simulations of neuronal
models.
PMID- 25128232
TI - Calcium channels for endocytosis.
PMID- 25128235
TI - A study on stability and medical implications for a complex delay model for CML
with cell competition and treatment.
AB - We study a mathematical model describing the dynamics of leukemic and normal cell
populations (stem-like and differentiated) in chronic myeloid leukemia (CML).
This model is a system of four delay differential equations incorporating three
types of cell division. The competition between normal and leukemic stem cell
populations for the common microenvironment is taken into consideration. The
stability of one steady state is investigated. The results are discussed via
their medical interpretation.
PMID- 25128236
TI - Economic principles in communication: an experimental study.
AB - This paper experimentally investigates how economic principles affect
communication. In a simple sender-receiver game with common interests over
payoffs, the sender can send a signal without a pre-given meaning in an
infrequent or frequent state of the world. When the signal is costly, several
theories (focal point theory, the intuitive criterion, evolutionary game theory)
predict an efficient separating equilibrium, where the signal is sent in the
infrequent state of the world (also referred to as Horn's rule). To analyze
whether Horn's rule applies, and if so, which theory best explains it, we develop
and test variants of the sender-receiver game where the theories generate
discriminatory hypotheses. In costly signaling variants, our participants follow
Horn's rule most of the time, in a manner that is best explained by focal point
theory. In costless signaling variants, evolutionary game theory best explains
our results. Here participants coordinate significantly more (less) often on a
separating equilibrium where the signal is sent in the frequent state if they are
primed to associate the absence of a signal with the infrequent (frequent) state
of the world. We also find indications that a similar priming effect applies to
costly signals. Thus, while the frequency with which participants follow Horn's
rule in costly signaling variants is best explained by Horn's rule, the priming
effect shows that some of our participants' behavior is best explained by
evolutionary game theory even when signals are costly.
PMID- 25128234
TI - Fluoroscopic guidance for placing a double lumen endotracheal tube in adults.
AB - OBJECTIVE: The aim of this study was to assess the right placement of the double
lumen endotracheal tube with fluoroscopic guidance, which is used in first
intention prior to the fiberscope in our institution. METHODS: This was a
prospective observational study. The study was conducted in vascular and thoracic
operating rooms. We enrolled 205 patients scheduled for thoracic surgery, with
ASA physical statuses of I (n = 37), II (n = 84), III (n = 80), and IV (n = 4).
Thoracic procedures were biopsy (n = 20), wedge (n = 34), culminectomy (n = 6),
lobectomy (n = 82), pneumonectomy (n = 4), sympathectomy (n = 9), symphysis (n =
47), and thymectomy (n = 3). The intubation with a double lumen tube was
performed with the help of a laryngoscope. Tracheal and bronchial balloons were
inflated and auscultation was performed after right and left exclusions. One shot
was performed to locate the position of the bronchial tube and the hook.
Fluoroscopic guidance was used to relocate the tube in case of a wrong position.
When the fluoroscopic guidance failed to position the tube, a fiberscope was
used. Perioperative collapse of the lung was assessed by the surgeon during the
surgery. RESULTS: Correct fluoroscopic image was obtained after the first attempt
in 58.5% of patients therefore a misplaced position was encountered in 41.5%. The
fluoroscopic guidance allowed an exact repositioning in 99.5% of cases, and the
mean duration of the procedure was 8 minutes. A fiberscope was required to move
the hook for one patient. We did not notice a moving of the double lumen
endotracheal tube during the surgery. The surgeon satisfaction was 100%.
CONCLUSION: The fluoroscopy evidenced the right position of the double lumen tube
and allowed a right repositioning in 99.5% of patients with a very simple
implementation.
PMID- 25128237
TI - Wing motion transformation to evaluate aerodynamic coupling in flapping wing
flight.
AB - Whether the remarkable flight performance of insects is because the animals
leverage inherent physics at this scale or because they employ specialized neural
feedback mechanisms is an active research question. In this study, an empirically
derived aerodynamics model is used with a transformation involving a delay and a
rotation to identify a class of kinematics that provide favorable roll-yaw
coupling. The transformation is also used to transform both synthetic and
experimentally measured wing motions onto the manifold representing proverse yaw
and to quantify the degree to which freely flying insects make use of passive
aerodynamic mechanisms to provide proverse roll-yaw turn coordination. The
transformation indicates that recorded insect kinematics do act to provide
proverse yaw for a variety of maneuvers. This finding suggests that passive
aerodynamic mechanisms can act to reduce the neural feedback demands of an
insect's flight control strategy.
PMID- 25128238
TI - Effect of treatment on the global dynamics of delayed pathological angiogenesis
models.
AB - For three different types of angiogenesis models with variable delays, we
consider either continuous or impulse therapy that eradicates tumor cells and
suppresses angiogenesis. For the cancer-free solution, explicit conditions of
global stability for the continuous and impulsive systems are obtained, together
with delay-dependent estimates for the rates of decay for the tumor volume and
pathological angiogenesis.
PMID- 25128241
TI - Antiphospholipid syndrome and acute myocardial infarction: treatment with
thrombectomy and abciximab.
AB - Antiphospholipid syndrome (APS) is an autoimmune coagulation disorder that
manifests clinically as venous and arterial thrombosis, and may affect any tissue
or organ. Coronary artery involvement, however, is very rare. Case reports in the
literature describing patients with coronary acute syndrome and APS treated with
coronary angioplasty show conflicting results. We report an adult male patient
with APS who presented with an acute myocardial infarction. Given the high risk
of thrombosis in these patients, he was treated percutaneously with thrombectomy
and abciximab. We review the few cases of coronary angioplasty in patients with
APS reported to date. To our knowledge, this is the first case in which acute
myocardial infarction due to thrombotic coronary occlusion was treated with
thrombectomy and abciximab without stenting the artery.
PMID- 25128247
TI - [Clinical analysis and surgical results of 58 paranasal sinus mucoceles].
AB - INTRODUCTION: Mucoceles are slow-growing, benign lesions found in the paranasal
sinuses that are locally destructive, causing bony resorption an displacement of
adjacent structures. We present our experience in the surgical treatment of these
lesions. METHODS: This was a retrospective review of 58 paranasal sinus mucoceles
in 54 patients between 1989 and 2012. We describe patient age and sex, mucocele
location, clinical features, surgical approaches employed, recurrence and
complications. RESULTS: The mean age of patients in this series was 59 years;
there were 31 males (57%) and 23 females (43%). Thirty-two cases (55%) were
located in the frontal or ethmoid-frontal system, 8 (14%) in the ethmoid sinus,
14 (24%) in the maxillary sinus and 4 (7%) in sphenoid sinus. Predisposing
factors were present in 55% of the patients and 45% cases were primary.
Endoscopic treatment was given to 71% of mucocele patients, while 29% were
treated with external or combined approaches. Recurrence appeared in 4 patients
(7%), 2 in the endoscopic surgery group and 2 in the external surgery group.
CONCLUSIONS: The procedure of choice for management of paranasal sinus mucoceles
is endoscopic drainage. It is a safe approach that gives good results.
PMID- 25128240
TI - Analysis of natural and induced variation in tomato glandular trichome flavonoids
identifies a gene not present in the reference genome.
AB - Flavonoids are ubiquitous plant aromatic specialized metabolites found in a
variety of cell types and organs. Methylated flavonoids are detected in secreting
glandular trichomes of various Solanum species, including the cultivated tomato
(Solanum lycopersicum). Inspection of the sequenced S. lycopersicum Heinz 1706
reference genome revealed a close homolog of Solanum habrochaites MOMT1 3'/5'
myricetin O-methyltransferase gene, but this gene (Solyc06g083450) is missing the
first exon, raising the question of whether cultivated tomato has a distinct 3'
or 3'/5' O-methyltransferase. A combination of mining genome and cDNA sequences
from wild tomato species and S. lycopersicum cultivar M82 led to the
identification of Sl-MOMT4 as a 3' O-methyltransferase. In parallel, three
independent ethyl methanesulfonate mutants in the S. lycopersicum cultivar M82
background were identified as having reduced amounts of di- and trimethylated
myricetins and increased monomethylated myricetin. Consistent with the hypothesis
that Sl-MOMT4 is a 3' O-methyltransferase gene, all three myricetin methylation
defective mutants were found to have defects in MOMT4 sequence, transcript
accumulation, or 3'-O-methyltransferase enzyme activity. Surprisingly, no MOMT4
sequence is found in the Heinz 1706 reference genome sequence, and this cultivar
accumulates 3-methyl myricetin and is deficient in 3'-methyl myricetins,
demonstrating variation in this gene among cultivated tomato varieties.
PMID- 25128239
TI - Role of transcription factor yin yang 1 in manganese-induced reduction of
astrocytic glutamate transporters: Putative mechanism for manganese-induced
neurotoxicity.
AB - Astrocytes are the most abundant non-neuronal glial cells in the brain. Once
relegated to a mere supportive role for neurons, contemporary dogmas ascribe
multiple active roles for these cells in central nervous system (CNS) function,
including maintenance of optimal glutamate levels in synapses. Regulation of
glutamate levels in the synaptic cleft is crucial for preventing excitotoxic
neuronal injury. Glutamate levels are regulated predominantly by two astrocytic
glutamate transporters, glutamate transporter 1 (GLT-1) and glutamate aspartate
transporter (GLAST). Indeed, the dysregulation of these transporters has been
linked to several neurodegenerative diseases such as amyotrophic lateral
sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD), as well
as manganism, which is caused by overexposure to the trace metal, manganese (Mn).
Although Mn is an essential trace element, its excessive accumulation in the
brain as a result of chronic occupational or environmental exposures induces a
neurological disorder referred to as manganism, which shares common pathological
features with Parkinsonism. Mn decreases the expression and function of both
GLAST and GLT-1. Astrocytes are commonly targeted by Mn, and thus reduction in
astrocytic glutamate transporter function represents a critical mechanism of Mn
induced neurotoxicity. In this review, we will discuss the role of astrocytic
glutamate transporters in neurodegenerative diseases and Mn-induced
neurotoxicity.
PMID- 25128248
TI - Relative contributions of negative symptoms, insight, and coping strategies to
quality of life in stable schizophrenia.
AB - The purpose of this cross-sectional study was to examine the relative
contributions of negative symptomatology, insight, and coping to quality of life
(QOL) in a sample of 92 consecutive outpatients with stable schizophrenia
referring to the Department of Neuroscience, Psychiatric Section, University of
Turin, Struttura Semplice di Coordinamento a Valenza Dipartimentale (SSCVD),
Department of Mental Health ASL TO1, Molinette, Italy, in the period between July
2009 and July 2011. In order to assess the specific effect of negative symptoms
on QOL and the possible mediating role of insight and coping, two mediation
hypotheses were tested, using multiple regression analyses specified by Baron and
Kenny (1986). Our findings suggest that (a) higher negative symptoms predict a
worse Quality of Life Scale (QLS) intrapsychic foundations (IF) subscale score;
(b) attribution of symptoms and coping-social diversion have a direct and
positive association with QLS-IF; (c) patients high in negative symptoms are less
likely to use attribution of symptoms and coping-social diversion; and (d)
attribution of symptoms and coping-social diversion act as partial mediators in
the negative symptoms-QOL relationship. The prediction model accounts for 45.3%
of the variance of the QLS-IF subscale score in our sample. In conclusion, our
results suggest that insight and coping-social diversion substantially contribute
to QOL in patients with higher negative symptoms. These factors are potentially
modifiable from specific therapeutic interventions, which can produce
considerable improvements in the QOL of this population.
PMID- 25128249
TI - An investigation into reasoning biases, mood and cognitive state, and subclinical
delusional ideation.
AB - Following research on reasoning and the continuum of delusional ideation, the
present study attempted to investigate the impact of different experimentally
induced states (stress, paranoia, and neutral) on the jumping-to-conclusions
reasoning bias in individuals with varying levels of subclinical delusional
ideation (SDI). Participants (N=117) completed a measure of subclinical
delusional ideation (the Peters et al. Delusions Inventory or PDI; Peters et al.,
1999); and were randomly assigned to receive one of two experimental inductions
(stress or paranoia), or no experimental induction; their performance on two
probabilistic reasoning tasks--one easy and one challenging--was assessed.
Although no differences were found between individuals with high vs. low
subclinical delusional ideation in the no induction condition or following the
paranoia induction, in the stress-induction condition, individuals with high
levels of subclinical delusional ideation were significantly less likely to jump
to conclusions on the easy reasoning task. No significant effects emerged on the
more challenging task. Assessment of post-test paranoid thinking indicated our
paranoia induction did not have its intended effect. Importantly, because there
was no pre-test of anxiety, paranoid thinking, or reasoning to determine if they
shifted after the inductions, results need to be interpreted with caution.
PMID- 25128250
TI - Post-traumatic psychological changes among survivors of the Lushan earthquake
living in the most affected areas.
AB - The primary objective of our study was to investigate both the negative and
positive psychological changes following the Lushan earthquake, and to explore
the factors associated with psychological changes. Multi-stage random sampling
was used to select respondents from Lushan County, Sichuan Province, China. A
simplified Chinese version of the short form of Changes in Outlook Questionnaire
(CiOQ-S) was used to assess psychological changes in earthquake survivors.
Descriptive statistics, t-tests, ANOVA and stepwise linear regression analysis
were used for data analysis. A total of 4972 respondents were investigated in the
cross-sectional study. The mean scores of the positive and negative psychological
changes were 26.61 and 8.12, respectively. The factors associated with positive
psychological changes included ethnic minority, high level of education, high
household income, not injured in the earthquake, not trapped during the
earthquake, and having experienced the Wenchuan earthquake. The factors
associated with negative psychological changes included female gender, ethnic
minority, low household income, history of diseases, injured during the
earthquake, and trapped during the earthquake. The current analysis helps expand
our knowledge of the negative and positive psychological changes that may occur
following an earthquake experience.
PMID- 25128251
TI - Differences in the developmental patterns of depression with and without
additional somatic symptoms.
AB - Depression accompanied by somatic symptoms ("somatic" depression) has been found
to differ from depression without the additional symptoms ("pure" depression) in
their gender ratio, their association with measures of perceived gender
inequality taken from both respondents and their parents, and in their response
to pharmacological treatment. Further evidence of the distinction between the two
syndromes might come from differential patterns of development. Data on the
annual incidence of new cases of depression exhibited by a representative sample
of respondents aged 12-19 came from the National household survey on drug use and
health. Between early adolescence (ages 12-14) and late adolescence (ages 15-19),
female respondents exhibited a much larger increase in somatic depression than in
pure depression. Males did not exhibit the same pattern. These results further
support the hypothesis that somatic and pure depressions are two distinct
disorders.
PMID- 25128252
TI - Still in the closet: the invisible minority in medical education.
AB - BACKGROUND: To investigate the relationship between sexual orientation and gender
identity in regard to levels of depression; levels of perceived social support;
comfort with disclosure of orientation; and the lesbian, gay, bisexual, and
transgender (LGBT) campus climate. METHODS: E-mail invitations to participate in
the current cross-sectional questionnaire-based study were sent to all thirty US
osteopathic medical schools in August 2012; six schools responded and
disseminated the survey to their students. Participating students completed an
anonymous web-based survey, and informed consent was obtained when they accessed
the survey. The survey was designed specifically for the current study but
contained scales used with permission from previously published research.
Analysis procedures included nonparametric tests, one-way analysis of variance
and Pearson's correlations. RESULTS: Of the 4112 students invited to participate
in the survey, 1334 (32.4%) completed it. Approximately 85% of respondents self
identified as heterosexual only. No respondents identified as transgender. In
general, LGB students indicated higher levels of depression (P < .001), slightly
lower levels of perceived social support (P < .001), and more discomfort with
disclosure of sexual orientation (P < .001). A majority of students rated their
campus climate as noninclusive. CONCLUSIONS: Results of the current study
indicated a relationship between sexual orientation and depression, perceived
social support, comfort with disclosure of orientation, and the LGBT campus
climate in osteopathic medical students. In the future, osteopathic medical
schools should consider closely examining their campus culture in order to create
a more positive and inclusive environment for all its students.
PMID- 25128253
TI - Reply: To PMID 24561105.
PMID- 25128254
TI - Intraoperative hyperkalemia induced by administration of trimethoprim
sulfamethoxazole in a patient receiving angiotensin receptor blockers.
PMID- 25128255
TI - Cluster-based computational methods for mass univariate analyses of event-related
brain potentials/fields: A simulation study.
AB - BACKGROUND: In recent years, analyses of event related potentials/fields have
moved from the selection of a few components and peaks to a mass-univariate
approach in which the whole data space is analyzed. Such extensive testing
increases the number of false positives and correction for multiple comparisons
is needed. METHOD: Here we review all cluster-based correction for multiple
comparison methods (cluster-height, cluster-size, cluster-mass, and threshold
free cluster enhancement - TFCE), in conjunction with two computational
approaches (permutation and bootstrap). RESULTS: Data driven Monte-Carlo
simulations comparing two conditions within subjects (two sample Student's t
test) showed that, on average, all cluster-based methods using permutation or
bootstrap alike control well the family-wise error rate (FWER), with a few
caveats. CONCLUSIONS: (i) A minimum of 800 iterations are necessary to obtain
stable results; (ii) below 50 trials, bootstrap methods are too conservative;
(iii) for low critical family-wise error rates (e.g. p=1%), permutations can be
too liberal; (iv) TFCE controls best the type 1 error rate with an attenuated
extent parameter (i.e. power<1).
PMID- 25128257
TI - Digital filter design for electrophysiological data--a practical approach.
AB - BACKGROUND: Filtering is a ubiquitous step in the preprocessing of
electroencephalographic (EEG) and magnetoencephalographic (MEG) data. Besides the
intended effect of the attenuation of signal components considered as noise,
filtering can also result in various unintended adverse filter effects
(distortions such as smoothing) and filter artifacts. METHOD: We give some
practical guidelines for the evaluation of filter responses (impulse and
frequency response) and the selection of filter types (high-pass/low-pass/band
pass/band-stop; finite/infinite impulse response, FIR/IIR) and filter parameters
(cutoff frequencies, filter order and roll-off, ripple, delay and causality) to
optimize signal-to-noise ratio and avoid or reduce signal distortions for
selected electrophysiological applications. RESULTS: Various filter
implementations in common electrophysiology software packages are introduced and
discussed. Resulting filter responses are compared and evaluated. CONCLUSION: We
present strategies for recognizing common adverse filter effects and filter
artifacts and demonstrate them in practical examples. Best practices and
recommendations for the selection and reporting of filter parameters,
limitations, and alternatives to filtering are discussed.
PMID- 25128258
TI - Radical resection of a Shamblin type III carotid body tumour without cerebro
neurological deficit: Improved technique with preoperative embolization and
carotid stenting.
AB - The surgical resection of a large unfavourable Shamblin type III carotid body
tumour (CBT) can be very challenging technically, with many potential significant
complications. Preoperative embolization aids in shrinking the lesion, reducing
intraoperative blood loss, and improving visualization of the surgical field.
Preoperative internal carotid artery (ICA) stenting aids in reinforcing the
arterial wall, thereby providing a better dissection plane. A woman presented to
our institution with a large right-sided CBT. Failure of the preoperative
temporary balloon occlusion (TBO) test emphasized the importance of
intraoperative preservation of the ipsilateral ICA. A combination of both
preoperative embolization and carotid stenting allowed a less hazardous radical
resection of the CBT. An almost bloodless surgical field permitted meticulous
dissection, hence reducing the risk of intraoperative vascular and nerve injury.
Embolization and carotid stenting prior to surgical resection should be
considered in cases with bilateral CBT or a skull base orientated high CBT, and
for those with intracranial extension and patients who have failed the TBO test.
PMID- 25128256
TI - Non-causal spike filtering improves decoding of movement intention for
intracortical BCIs.
AB - BACKGROUND: Multiple types of neural signals are available for controlling
assistive devices through brain-computer interfaces (BCIs). Intracortically
recorded spiking neural signals are attractive for BCIs because they can in
principle provide greater fidelity of encoded information compared to
electrocorticographic (ECoG) signals and electroencephalograms (EEGs). Recent
reports show that the information content of these spiking neural signals can be
reliably extracted simply by causally band-pass filtering the recorded
extracellular voltage signals and then applying a spike detection threshold,
without relying on "sorting" action potentials. NEW METHOD: We show that
replacing the causal filter with an equivalent non-causal filter increases the
information content extracted from the extracellular spiking signal and improves
decoding of intended movement direction. This method can be used for real-time
BCI applications by using a 4ms lag between recording and filtering neural
signals. RESULTS: Across 18 sessions from two people with tetraplegia enrolled in
the BrainGate2 pilot clinical trial, we found that threshold crossing events
extracted using this non-causal filtering method were significantly more
informative of each participant's intended cursor kinematics compared to
threshold crossing events derived from causally filtered signals. This new method
decreased the mean angular error between the intended and decoded cursor
direction by 9.7 degrees for participant S3, who was implanted 5.4 years prior
to this study, and by 3.5 degrees for participant T2, who was implanted 3 months
prior to this study. CONCLUSIONS: Non-causally filtering neural signals prior to
extracting threshold crossing events may be a simple yet effective way to
condition intracortically recorded neural activity for direct control of external
devices through BCIs.
PMID- 25128259
TI - Wound ballistics of firearm-related injuries--part 1: missile characteristics and
mechanisms of soft tissue wounding.
AB - Firearm-related injuries are caused by a wide variety of weapons and projectiles.
The kinetic energy of the penetrating projectile defines its ability to disrupt
and displace tissue, whereas the actual tissue damage is determined by the mode
of energy release during the projectile-tissue interaction and the particular
characteristics of the tissues and organs involved. Certain projectile factors,
namely shape, construction, and stability, greatly influence the rate of energy
transfer to the tissues along the wound track. Two zones of tissue damage can be
identified, the permanent cavity created by the passage of the bullet and a
potential area of contused tissue surrounding it, produced mainly by temporary
cavitation which is a manifestation of effective high-energy transfer to tissue.
Due to the complex nature of these injuries, wound assessment and the type and
extent of treatment required should be based on an understanding of the various
mechanisms contributing to tissue damage.
PMID- 25128260
TI - Auto-fluorescence of the bone and its use for delineation of bone necrosis.
AB - Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a challenging
complication of long-term bisphosphonate treatment. Currently, the drawback in
the surgical management of BRONJ is the difficulty distinguishing between viable
and necrotic bone. Intraoperative bone fluorescence induced by tetracyclines has
been shown to be a valuable aid to overcome this problem. In this technical note
we report the finding that viable bone is auto-fluorescent using the VELscope Vx
fluorescence lamp. Necrotic bone shows an altered fluorescence pattern (pale or
no fluorescence). Thus it is suggested that auto-fluorescence of bone might be of
similar use during the surgical therapy of BRONJ.
PMID- 25128261
TI - Complications associated with inferior alveolar nerve repositioning for dental
implant placement: a systematic review.
AB - Inferior alveolar nerve (IAN) repositioning has been used widely in recent years
as an alternative approach for dental implant placement in the atrophic posterior
mandible. The aim of this study was to answer the question: What are the
complications associated with IAN repositioning? A systematic literature review
performed in accordance with the PRISMA statement, using the PubMed (MEDLINE),
Cochrane Library, and Scopus databases, identified a total of 116 articles
related to this technique. Of those articles, 24 were included in the final
review. Lateralization was the chosen technique in seven studies, transposition
in 15 studies, and two studies reported both techniques. The longest follow-up
period was 49.1 months and the shortest 6 months. Of the patients who underwent
lateralization, 95.9% initially showed a neurosensory disturbance, and the
condition remained at the end of the study for 3.4% of those patients. With
regard to the patients who underwent transposition, neurosensory alterations were
observed in 58.9% of patients initially, and the condition remained for 22.1% of
those affected at the end of the study. Only one study found no neurosensory
disturbance at any time. More data consolidation is necessary to determine
scientifically if, which, and when the IAN repositioning technique can be
recommended.
PMID- 25128262
TI - Comparison of related complications: sentinel node biopsy versus elective neck
dissection.
AB - Sentinel node biopsy (SNB) is considered a feasible neck staging tool in early
oral squamous cell carcinoma. The aim of this study was to compare postoperative
morbidity in patients who had undergone SNB and elective neck dissection (END).
Seventy-three consecutive patients were included between the years 2005 and 2009.
The patients were divided into two groups according to neck management: SNB and
END groups. Kaplan-Meier survival analysis was used to compare disease-free
survival (DFS) and overall survival (OS) between the groups. Shoulder function,
length of the surgical scar, and the degree of cervical lymphoedema were
assessed. Neck haematoma and the presence of oro-cervical communication were also
analyzed. Thirty-two patients underwent SNB and 41 underwent an END (levels I
III). Seven regional recurrences were recorded in the END group. Three neck
recurrences occurred in the SNB group. No significant differences were found in
DFS or OS between the groups. There were statistically significant differences
between the groups in shoulder function and average scar length. However,
differences in degree of lymphoedema were not statistically significant. Neck
hematomas and oro-cervical communications occurred only in the END group. From
this study, it can be concluded that SNB presents less postoperative morbidity
than END.
PMID- 25128263
TI - Wound ballistics of firearm-related injuries--part 2: mechanisms of skeletal
injury and characteristics of maxillofacial ballistic trauma.
AB - Maxillofacial firearm-related injuries vary in extent and severity because of the
characteristics and behaviour of the projectile(s), and the complexity of the
anatomical structures involved, whereas the degree of tissue disruption is also
affected by the distance of the shot. In low-energy injuries there is limited
damage to the underlying skeleton, which usually dominates the clinical picture,
dictating a more straightforward therapeutic approach. High-energy injuries are
associated with extensive hard and soft tissue disruption, and are characterized
by a surrounding zone of damaged tissue that is prone to progressive necrosis as
a result of compromised blood supply and wound sepsis. Current treatment
protocols for these injuries emphasize the importance of serial debridement for
effective wound control while favouring early definitive reconstruction.
PMID- 25128264
TI - MicroRNAs: Small molecules with big roles in neurodevelopment and diseases.
AB - MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that play
important roles in the development and functions of the brain. Extensive studies
have revealed critical roles for miRNAs in brain development and function.
Dysregulation or altered expression of miRNAs is associated with abnormal brain
development and pathogenesis of neurodevelopmental diseases. This review serves
to highlight the versatile roles of these small RNA molecules in normal brain
development and their association with neurodevelopmental disorders, in
particular, two closely related neuropsychiatric disorders of neurodevelopmental
origin, schizophrenia and bipolar disorder.
PMID- 25128266
TI - Poorer glycaemic control in type 1 diabetes is associated with reduced self
management and poorer perceived health: a cross-sectional study.
AB - AIMS: Many people with type 1 diabetes do not achieve optimal treatment targets
despite high patient and professional input. To investigate the reasons
underlying suboptimal control we have studied clinical characteristics and self
management behaviours in adults with type 1 diabetes attending a large treatment
centre. METHODS: A questionnaire-based enquiry into self-care behaviours of 380
patients with type 1 diabetes (mean age: 48 (+/-15) years and mean duration of
diabetes: 26 (+/-15) years), linked with validated measures of impact of
treatment on perceived health and hypoglycaemia recognition (Insulin Treatment
Satisfaction Questionnaire; and EuroQoL EQ-5D, Gold score) and retrospective case
note review of biomedical parameters. The data were analysed using chi-square
test, ANOVA, ANCOVA and post-hoc procedures (Tukey's-b) in SPSS-version 18. The
minimum significance level was accepted as 0.05. RESULTS: Sixty three percent of
participants used multiple daily injections; 36% continuous subcutaneous insulin
infusion. Mean HbA1c was 7.7% (+/-1.2) [61+/--10mmol/mol]; 30% had impaired
hypoglycaemia awareness (IHA). Factors significantly related to poor glycaemic
control with IHA were longer duration of diabetes (p=0.01); less frequent glucose
self-monitoring (p=0.05); and low level of patient-set glucose targets (p<0.001).
Patients with IHA and poorer control had significantly lower insulin treatment
satisfaction (p<0.001); and perceived health (p<0.001). CONCLUSIONS: Suboptimal
biomedical outcomes in adults with type 1 diabetes attending a specialist
intensified insulin therapy clinic are associated with longer duration of
diabetes, fewer self-management behaviours and a trend towards poorer perceived
health. These data suggest a need for greater emphasis on integration of
psychological and self-management support with intensive medical management of
type 1 diabetes.
PMID- 25128267
TI - Focusing on potential sources of glucose fluctuations in type 1 and type 2
diabetes: which kind of patient, what kind of glycemic variability and which
confounding factors?
PMID- 25128265
TI - A comparative morphological, electrophysiological and functional analysis of axon
regeneration through peripheral nerve autografts genetically modified to
overexpress BDNF, CNTF, GDNF, NGF, NT3 or VEGF.
AB - The clinical outcome of microsurgical repair of an injured peripheral nerve with
an autograft is suboptimal. A key question addressed here is: can axon
regeneration through an autograft be further improved? In this article the impact
of six neurotrophic factors (BDNF, CNTF, GDNF, NGF, NT3 or VEGF) on axon
regeneration was compared after delivery to a 1cm long nerve autograft by gene
therapy. To distinguish between early and late effects, regeneration was assessed
at 2 and 20weeks post-surgery by histological, electrophysiological and
functional analysis. BDNF, GDNF and NGF exhibited a spectrum of effects,
including early stimulatory effects on axons entering the autograft and excessive
axon growth and Schwann cell proliferation at 20weeks post-surgery. Persistent
expression of these factors in autografts interfered with target cell
reinnervation and functional recovery in a modality specific way. Autografts
overexpressing VEGF displayed hypervascularization, while grafts transduced with
CNTF and NT3 were indistinguishable from control grafts. These three factors did
not have detectable pro-regenerative effects. In conclusion, autograft-based
repair combined with gene therapy for three of the six growth factors
investigated (BDNF, GDNF, NGF) showed considerable promise since these factors
enhanced modality specific axon outgrowth in autografts. The remarkable and
selective effects of BDNF, GDNF and NGF on motor or sensory regeneration will be
exploited in future experiments that aim to carefully regulate their temporal and
spatial expression since this has the potential to overcome the adverse effects
on long-distance regeneration observed after uncontrolled delivery.
PMID- 25128268
TI - Treatment costs of psoriasis in a tertiary-level clinic.
AB - BACKGROUND: The costs of psoriasis to a tertiary-level clinic vary considerably
depending on the country of study and methods used. Hospitalisation and
phototherapy have been significant cost components. This study was performed to
estimate the distribution and relative magnitude of the costs of psoriasis to a
tertiary-level clinic. METHODS: Based on 233 patients, outpatient and
phototherapy visits and the days hospitalised were collected from the treatment
provider's records. The visit costs represented true costs, used to charge the
final payers. Patients were analysed according to their treatment modalities.
RESULTS: On average, hospitalised patients (3.4%) had 31-fold higher total costs
than non-hospitalised patients (p < 0.0001). The costs of hospitalisations formed
45% of all the treatment costs to the entire study population. Phototherapy
accumulated 19% of the overall treatment costs. Patients receiving biological
drugs or both phototherapy and traditional systemic therapy had the highest costs
of treatment. CONCLUSIONS: The current study indicates that a small percentage of
all psoriasis patients generate a large proportion of the overall costs to a
tertiary-level hospital. Treatment modality has a significant effect on the costs
to a tertiary-level hospital.
PMID- 25128269
TI - Airbrushed composite polymer Zr-ACP nanofiber scaffolds with improved cell
penetration for bone tissue regeneration.
AB - Electrospun polymer nanofibers have multiple applications in the tissue
engineering field despite limited cell penetration within the scaffolds and slow
synthesis rates. Airbrushing, a proposed alternative to traditional
electrospinning, is a technique capable of synthesizing open structure nanofiber
scaffolds at high rates. In this study, three biocompatible polymers-poly-D,L
lactic acid (P-DL-LA), polycaprolactone (PCL), and poly(methyl methacrylate)
(PMMA), were airbrushed to form networks for bone tissue regeneration. All three
polymers were loaded with up to 20% (w/w) zirconium-modified amorphous calcium
phosphate (Zr-ACP). A simple one-step mix and straightforward material deposition
yielded open structure networks with well-distributed Zr-ACP. Cell penetration
within the airbrushed scaffolds was found to be more than twice the cell
penetration within conventional electrospun networks. The airbrushed polymer
network supported cell growth and differentiation. Cells grown on the Zr-ACP in P
DL-LA fibers exhibited improved levels of osteocalcin protein with an increase in
the Zr-ACP content by day 16. This airbrushing method promises to be a viable and
attractive alternative to currently used electrospinning techniques in the
formation of composite 3D nanofiber scaffolds for tissue engineering
applications.
PMID- 25128270
TI - Timing of enteral nutrition in acute pancreatitis: meta-analysis of individuals
using a single-arm of randomised trials.
AB - INTRODUCTION: In acute pancreatitis, enteral nutrition (EN) reduces the rate of
complications, such as infected pancreatic necrosis, organ failure, and
mortality, as compared to parenteral nutrition (PN). Starting EN within 24 h of
admission might further reduce complications. METHODS: A literature search for
trials of EN in acute pancreatitis was performed. Authors of eligible trials were
requested to provide the data of all patients in the EN-arm of their trials. A
meta-analysis of individual patient data was performed. The cohort of patients
with EN was divided into patients receiving EN within 24 h or after 24 h of
admission. Multivariable logistic regression, adjusting for predicted disease
severity and trial, was used to study the effect of timing of EN on a composite
endpoint of infected pancreatic necrosis, organ failure, or mortality. RESULTS:
Observational data from 165 individuals from 8 randomised trials were obtained;
100 patients with EN within 24 h and 65 patients with EN after 24 h of admission.
In the multivariable model, EN started within 24 h of admission compared to EN
started after 24 h of admission, reduced the composite endpoint from 45% to 19%
(adjusted odds ratio [OR] of 0.44; 95% confidence interval [CI] 0.20-0.96).
Within the composite endpoint, organ failure was reduced from 42% to 16%
(adjusted OR 0.42; 95% CI 0.19-0.94). CONCLUSIONS: In this meta-analysis of
observational data from individuals with acute pancreatitis, starting EN within
24 h after hospital admission, compared with after 24 h, was associated with a
reduction in complications.
PMID- 25128272
TI - Antenatal corticosteroids 40 years on: we can do better.
PMID- 25128271
TI - Use of antenatal corticosteroids and tocolytic drugs in preterm births in 29
countries: an analysis of the WHO Multicountry Survey on Maternal and Newborn
Health.
AB - BACKGROUND: Despite the global burden of morbidity and mortality associated with
preterm birth, little evidence is available for use of antenatal corticosteroids
and tocolytic drugs in preterm births in low-income and middle-income countries.
We analysed data from the WHO Multicountry Survey on Maternal and Newborn Health
(WHOMCS) to assess coverage for these interventions in preterm deliveries.
METHODS: WHOMCS is a facility-based, cross-sectional survey database of birth
outcomes in 359 facilities in 29 countries, with data collected prospectively
from May 1, 2010, to Dec 31, 2011. For this analysis, we included deliveries
after 22 weeks' gestation and we excluded births that occurred outside a facility
or quicker than 3 h after arrival. We calculated use of antenatal corticosteroids
in women who gave birth between 26 and 34 weeks' gestation, when antenatal
corticosteroids are known to be most beneficial. We also calculated use in women
at 22-25 weeks' and 34-36 weeks' gestation. We assessed tocolytic drug use, with
and without antenatal corticosteroids, in spontaneous, uncomplicated preterm
deliveries at 26-34 weeks' gestation. FINDINGS: Of 303,842 recorded deliveries
after 22 weeks' gestation, 17,705 (6%) were preterm. 3900 (52%) of 7547 women who
gave birth at 26-34 weeks' gestation, 94 (19%) of 497 women who gave birth at 22
25 weeks' gestation, and 2276 (24%) of 9661 women who gave birth at 35-36 weeks'
gestation received antenatal corticosteroids. Rates of antenatal corticosteroid
use varied between countries (median 54%, range 16-91%; IQR 30-68%). Of 4677
women who were potentially eligible for tocolysis drugs, 1276 (27%) were treated
with bed rest or hydration and 2248 (48%) received no treatment. beta-agonists
alone (n=346, 7%) were the most frequently used tocolytic drug. Only 848 (18%) of
potentially eligible women received both a tocolytic drug and antenatal
corticosteroids. INTERPRETATION: Use of interventions was generally poor, despite
evidence for their benefit for newborn babies. A substantial proportion of
antenatal corticosteroid use occurred at gestational ages at which benefit is
controversial, and use of less effective or potentially harmful tocolytic drugs
was common. Implementation research and contextualised health policies are needed
to improve drug availability and increase compliance with best obstetric
practice. FUNDING: UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of
Research, Development and Research Training in Human Reproduction (HRP); WHO;
USAID; Ministry of Health, Labour and Welfare of Japan; Gynuity Health Projects.
PMID- 25128273
TI - The US diabetes epidemic: tip of the iceberg.
PMID- 25128274
TI - Trends in lifetime risk and years of life lost due to diabetes in the USA, 1985
2011: a modelling study.
AB - BACKGROUND: Diabetes incidence has increased and mortality has decreased greatly
in the USA, potentially leading to substantial changes in the lifetime risk of
diabetes. We aimed to provide updated estimates for the lifetime risk of
development of diabetes and to assess the effect of changes in incidence and
mortality on lifetime risk and life-years lost to diabetes in the USA. METHODS:
We incorporated data about diabetes incidence from the National Health Interview
Survey, and linked data about mortality from 1985 to 2011 for 598 216 adults,
into a Markov chain model to estimate remaining lifetime diabetes risk, years
spent with and without diagnosed diabetes, and life-years lost due to diabetes in
three cohorts: 1985-89, 1990-99, and 2000-11. Diabetes was determined by self
report and was classified as any diabetes, excluding gestational diabetes. We
used logistic regression to estimate the incidence of diabetes and Poisson
regression to estimate mortality. FINDINGS: On the basis of 2000-11 data,
lifetime risk of diagnosed diabetes from age 20 years was 40.2% (95% CI 39.2
41.3) for men and 39.6% (38.6-40.5) for women, representing increases of 20
percentage points and 13 percentage points, respectively, since 1985-89. The
highest lifetime risks were in Hispanic men and women, and non-Hispanic black
women, for whom lifetime risk now exceeds 50%. The number of life-years lost to
diabetes when diagnosed at age 40 years decreased from 7.7 years (95% CI 6.5-9.0)
in 1990-99 to 5.8 years (4.6-7.1) in 2000-11 in men, and from 8.7 years (8.4-8.9)
to 6.8 years (6.7-7.0) in women over the same period. Because of the increasing
diabetes prevalence, the average number of years lost due to diabetes for the
population as a whole increased by 46% in men and 44% in women. Years spent with
diabetes increased by 156% in men and 70% in women. INTERPRETATION: Continued
increases in the incidence of diagnosed diabetes combined with declining
mortality have led to an acceleration of lifetime risk and more years spent with
diabetes, but fewer years lost to the disease for the average individual with
diabetes. These findings mean that there will be a continued need for health
services and extensive costs to manage the disease, and emphasise the need for
effective interventions to reduce incidence. FUNDING: None.
PMID- 25128275
TI - Tricyclic antidepressants exhibit variable pharmacological profiles at the
alpha(2A) adrenergic receptor.
AB - Antidepressant mechanisms of action remain shrouded in mystery, greatly hindering
our ability to develop therapeutics which can fully treat patients suffering from
depressive disorders. In an attempt to shed new light on this topic, we have
undertaken a series of studies investigating actions of tricyclic antidepressant
drugs (TCAs) at the alpha2A adrenergic receptor (AR), a centrally important
receptor, dysregulation of which has been linked to depression. Our previous work
established a particular TCA, desipramine, as an arrestin-biased alpha2AAR ligand
driving receptor endocytosis and downregulation but not canonical heterotrimeric
G protein-mediated signaling. The present work is aimed at broadening our
understanding of how members of the TCA drug class act at the alpha2AAR, as we
have selected the closely related but subtly different TCAs imipramine and
amitriptyline for evaluation. Our data demonstrate that these drugs do also
function as direct arrestin-biased alpha2AAR ligands. However, these data reveal
differences in receptor affinity and in the extent/nature of arrestin recruitment
to and endocytosis of alpha2AARs. Specifically, amitriptyline exhibits an
approximately 14-fold stronger interaction with the receptor, is a weaker driver
of arrestin recruitment, and preferentially recruits a different arrestin
subtype. Extent of endocytosis is similar for all TCAs studied so far, and occurs
in an arrestin-dependent manner, although imipramine uniquely retains a slight
ability to drive alpha2AAR endocytosis in arrestin-null cells. These findings
signify an important expansion of our mechanistic understanding of antidepressant
pharmacology, and provide useful insights for future medicinal chemistry efforts.
PMID- 25128276
TI - Aloperine attenuated neuropathic pain induced by chronic constriction injury via
anti-oxidation activity and suppression of the nuclear factor kappa B pathway.
AB - OBJECTIVE: To investigate whether aloperine (ALO) has antinociceptive effects on
neuropathic pain induced by chronic constriction injury, whether ALO reduces ROS
against neuropathic pain, and what are the mechanisms involved in ALO attenuated
neuropathic pain. METHODS: Mechanical and cold allodynia, thermal and mechanical
hyperalgesia and spinal thermal hyperalgesia were estimated by behavior methods
such as Von Frey filaments, cold-plate, radiant heat, paw pressure and tail
immersion on one day before surgery and days 7, 8, 10, 12 and 14 after surgery,
respectively. In addition, T-AOC, GSH-PX, T-AOC and MDA in the spinal cord (L4/5)
were measured to evaluate anti-oxidation activity of ALO on neuropathic pain.
Expressions of NF-kappaB and pro-inflammatory cytokines (TNF-alpha, IL-6, IL
1beta) in the spinal cord (L4/5) were analyzed by using Western blot. RESULTS:
Administration of ALO (80mg/kg and 40mg/kg, i.p.) significantly increased paw
withdrawal threshold, paw pressure, paw withdrawal latencies, tail-curling
latencies, T-AOC, GSH-PX and T-SOD concentration, reduced the numbers of paw
lifts and MDA concentration compared to CCI group. ALO attenuated CCI induced up
regulation of expressions of NF-kappaB, TNF-alpha, IL-6, IL-1beta at the dose of
80mg/kg (i.p.). Pregabalin produced similar effects serving as positive control
at the dose of 10mg/kg (i.p.). CONCLUSION: ALO has antinociceptive effects on
neuropathic pain induced by CCI. The antinociceptive effects of ALO against
neuropathic pain is related to reduction of ROS, via suppression of NF-kappaB
pathway.
PMID- 25128277
TI - Comparison of the efficacy of nickel-titanium rotary systems with or without the
retreatment instruments in the removal of gutta-percha in the apical third.
AB - BACKGROUND: The purpose of this study was to compare the efficacy of nickel
titanium rotary systems with or without the retreatment instruments in the
removal of gutta-percha from the apical third. METHODS: The systems compared were
as follows: ProTaper Universal (PT), ProTaper Universal Retreatment (PTr), Mtwo
(M2) and Mtwo Retreatment (M2r). Sixty extracted mandibular incisors were treated
with a crown-down technique and filled with gutta-percha and sealer. The apical
diameter was standardized in 0.30 mm, 1 mm from the apex. The teeth were
distributed into 4 experimental groups: PT, PTr, M2 and M2r. In PTr and M2r
groups, filling materials were removed by PTr/M2r followed by root canals
preparation up to a PT F4/M2 40; in groups PT/M2, the filling materials were
removed and the root canals were prepared by PT up to a PT F4/M2 up to a M2 40.
The roots were split and photomicrographing. The percentage of clean area in the
apical 5 mm was calculated using software. Data were analyzed with the Kruskal
Wallis test. RESULTS: Remaining material was found in all hemisections and there
was no statistically significant difference between the groups (p = 0.09).
Considering the surface of the canal walls of all teeth, the mean of the
percentage of clean area was 54%. CONCLUSIONS: Considering the applied
methodology, remaining filling material was found in all hemisections, regardless
of the retreatment technique and PT or M2 were as effective as PTr/PT or M2r/M2.
PMID- 25128278
TI - Comparison between rapid and slow palatal expansion: evaluation of selected
periodontal indices.
AB - OBJECTIVES: The aim of this pilot study was to evaluate the periodontal effects
during rapid palatal expansion (RPE) or slow palatal expansion (SPE) and to
compare them by means of some clinical indices, in order to establish the
possible differences and advantages of one of these treatments in periodontal
terms. METHODS: 10 patients (aged 6 to 7 years; average age 6.3 years) were
submitted to RPE treatment and other 10 patients (aged 6 to 8 years, average age
6.3 years) to SPE treatment. They were treated with the Haas expander. The
selected clinical indices (plaque index, PI; papillary bleeding index, PBI;
probing pocket depth, PPD) were collected three times during the treatment (t0,
detected 7 days after the periodontal prophylaxis, at the beginning of the active
orthodontic therapy; t1, detected during the active therapy; t2, detected after
retention). All measurements were performed by the same examiner. The protocol
was approved by the ethics committee. RESULTS: The effects of the prophylaxis
were excellent to control inflammation and dental plaque before the beginning of
the orthodontic-orthopaedic treatment, as in both the two groups, the PI and the
PBI values were equal to 0.In the group receiving slow expansion, the PPD
remained unchanged from t0 to t1, while it significantly increased from t0 to t1
in the group of rapid expansion. At t2 the values of the two groups returned to
be overlapping. CONCLUSIONS: Both rapid and slow expansion treatments present
potential irritation effect (increase of PI index and PBI index) on the
periodontium, suggested by the significant increase of PI and PBI from t0 to t1
in both the two groups; therefore prophylaxis and periodic controls are very
important. There are no long-term benefits that might be referred unequivocally
to one of the two treatments in terms of periodontal consequences, as
demonstrated by the lack of significant differences between the two groups at t2.
PMID- 25128279
TI - Functional genetic variation in the serotonin 5-HTTLPR modulates brain damage in
frontotemporal dementia.
AB - In frontotemporal dementia (FTD), nonmodifiable (genetic background) and
modifiable (cognitive reserve [CR]) factors might interact in affecting
frontotemporal damage. Serotoninergic dysfunction has been suggested as a key
factor in FTD pathogenesis. 5-HTTLPR polymorphism on SCLA4 gene modulates the
serotoninergic transmission. To evaluate the impact of 5-HTTLPR polymorphism on
regional cerebral blood flow (rCBF) and its possible interaction with CR, 76 FTD
patients with a 5-HTTLPR genotyping were recruited. All subjects underwent
neuropsychological assessment and single-photon emission computed tomography
imaging. Reserve index (RI) was computed from educational and occupational
attainments, as proxy measure of CR. 5-HTTLPR analysis evidenced 14 S/S, 24 L/L,
and 38 S/L carriers. No neuropsychological/behavioral differences were present.
At the same disease stage, L/L carriers have a greater bilateral frontal rCBF
decrease. Patients with higher RI had greater damage in right frontal and
temporal regions. The additive effect of 5-HTTLPR polymorphism and RI was
characterized by greater frontal rCBF deficit. 5-HTTLPR and CR act together to
counteract brain pathology in FTD. Further studies are warranted to test the
serotonin role in monogenic forms of FTD.
PMID- 25128281
TI - Iatrogenic traumatic intracranial aneurysm after endoscopic sinus surgery.
AB - Iatrogenic traumatic intracranial aneurysms are rare, but their clinical impact
is significant secondary to their risk of intracranial hemorrhage and in their
frequent complexity in management. We report an adult patient with a history of
chronic sinusitis who, while undergoing elective endoscopic polypectomy, suffered
an iatrogenic injury to an A2 segment branch of the left anterior cerebral
artery, resulting in a pseudoaneurysm. Management included endovascular coiling
and a bicoronal craniotomy approach, using a split-thickness cranial graft and
abdominal fat graft to repair the associated left cribriform plate defect.
PMID- 25128282
TI - Vasodilatation of multiple cerebral arteries in early stage of stroke-like
episode with MELAS.
AB - We describe a patient with mitochondrial myopathy, encephalopathy, lactic
acidosis, and stroke-like episodes (MELAS), with multiple cerebral
vasodilatations in a stroke-like episode visualised by using magnetic resonance
angiography (MRA) and CT angiography (CTA). In the acute stroke-like episode
stage, T2-weighted and fluid-attenuated inversion recovery MRI showed high
intensity areas in the left occipital area. In addition, MRA and CTA revealed
prominent dilatation of the left posterior cerebral artery and temporal branches
of the middle cerebral artery with focal hyperperfusions using CT perfusion (CTP)
that corresponded to the MRI. After 10 days, with the development of aphasia, MRI
indicated the lesions had spread to the temporal and parietal regions, and this
distribution was not confined to major vascular territories. The patient's
symptoms gradually improved, accompanied by the attenuation of MRI, CTA, and CTP
findings. These characteristic features along with the MRI changes that spread
beyond vascular boundaries and the multiple cerebral vasodilatations prior to the
development of clinical symptoms are not fully explained by the mitochondrial
angiopathy or cytopathy theories. These findings provide further evidence
supporting neuronal hyperexcitability in stroke-like episodes of MELAS.
PMID- 25128283
TI - The impact of prior knowledge from participant instructions in a mock crime P300
Concealed Information Test.
AB - In P300-Concealed Information Tests used with mock crime scenarios, the amount of
detail revealed to a participant prior to the commission of the mock crime can
have a serious impact on a study's validity. We predicted that exposure to crime
details through instructions would bias detection rates toward enhanced
sensitivity. In a 2 * 2 factorial design, participants were either informed
(through mock crime instructions) or naive as to the identity of a to-be-stolen
item, and then either committed (guilty) or did not commit (innocent) the crime.
Results showed that prior knowledge of the stolen item was sufficient to cause
69% of innocent-informed participants to be incorrectly classified as guilty.
Further, we found a trend toward enhanced detection rate for guilty-informed
participants over guilty-naive participants. Results suggest that revealing
details to participants through instructions biases detection rates in the P300
CIT toward enhanced sensitivity.
PMID- 25128280
TI - Pattern of brain atrophy rates in autopsy-confirmed dementia with Lewy bodies.
AB - Dementia with Lewy bodies (DLB) is characterized by preserved whole brain and
medial temporal lobe volumes compared with Alzheimer's disease dementia (AD) on
magnetic resonance imaging. However, frequently coexistent AD-type pathology may
influence the pattern of regional brain atrophy rates in DLB patients. We
investigated the pattern and magnitude of the atrophy rates from 2 serial MRIs in
autopsy-confirmed DLB patients (n = 20) and mixed DLB/AD patients (n = 22),
compared with AD (n = 30) and elderly nondemented control subjects (n = 15),
followed antemortem. DLB patients without significant AD-type pathology were
characterized by lower global and regional rates of atrophy, similar to control
subjects. The mixed DLB/AD patients displayed greater atrophy rates in the whole
brain, temporoparietal cortices, hippocampus and amygdala, and ventricle
expansion, similar to AD patients. In the DLB and DLB/AD patients, the atrophy
rates correlated with Braak neurofibrillary tangle stage, cognitive decline, and
progression of motor symptoms. Global and regional atrophy rates are associated
with AD-type pathology in DLB, and these rates can be used as biomarkers of AD
progression in patients with LB pathology.
PMID- 25128284
TI - Opioid-induced hyperalgesia (OIH): a real clinical problem or just an
experimental phenomenon?
AB - Although opioid-induced hyperalgesia (OIH) is mentioned as a potential cause of
opioid dose escalation without adequate analgesia, true evidence in support of
this notion is relatively limited. Most studies conducted in the context of acute
and experimental pain, which seemingly demonstrated evidence for OIH, actually
might have measured other phenomena such as acute opioid withdrawal or tolerance.
OIH studies in patients with chronic pain have used various experimental pain
models (such as cold pain tolerance or heat pain intensity). Therefore, the fact
that they have yielded inconsistent results is hard to interpret. Thus far, with
the exception of a few clinical case reports on OIH in patients with cancer pain
and one prospective study in patients with chronic neuropathic pain, evidence for
OIH in patients with chronic or cancer-related pain is lacking. Whether
experimental pain models are necessary for establishing the clinical diagnosis of
OIH, and which specific model is preferred, are yet to be determined.
PMID- 25128285
TI - C-reactive protein, depressive symptoms, and risk of diabetes: results from the
English Longitudinal Study of Ageing (ELSA).
AB - OBJECTIVES: Raised levels of C-reactive protein (CRP), an inflammatory biomarker,
and depressive symptoms are both independently linked to risk of diabetes. The
purpose of this study was to assess the joint association of CRP and depressive
symptomatology with diabetes incidence in a representative sample of English
people >=50 years old. METHOD: Data were from the English Longitudinal Study of
Ageing, a prospective study of community-dwelling older adults. The sample was
comprised of 4955 participants without self-reported doctor-diagnosed diabetes at
baseline. High CRP level was dichotomized as >3 mg/L. Elevated depressive
symptomatology was defined as >=4 using the 8-item Center for Epidemiologic
Studies Depression Scale. Incident diabetes was determined based on newly self
reported doctor-diagnosed diabetes. Cox proportional hazard regressions were used
to examine the association between CRP and depressive symptoms with incidence of
type 2 diabetes. RESULTS: During approximately 63.2 months of follow-up, 194
participants reported diabetes diagnosis. After adjustment for socio
demographics, lifestyle behaviors, clinical factors, and BMI, the hazard ratio
for diabetes was 1.63 (95% CI 0.88-3.01) for people with elevated depressive
symptoms only, 1.43 (95% CI 0.99-2.07) for people with high CRP only, and 2.03
(95% CI 1.14-3.61) for people with both high CRP and elevated depressive
symptoms. CONCLUSION: The presence of both high CRP levels and elevated
depressive symptoms was associated with risk of diabetes. Further investigation
into this relationship could aid in understanding the mechanisms underlying
inflammation, depression, and diabetes.
PMID- 25128286
TI - Understanding the impact of visual arts interventions for people living with
dementia: a realist review protocol.
AB - BACKGROUND: Arts-based activities are being increasingly suggested as a valuable
activity for people living with dementia in terms of countering the negative
aspects of their condition. The potential for such programmes to improve a broad
range of psychosocial outcomes is suggested in some studies. However, there is
largely an absence of rigorous methodology to demonstrate the benefits, and
research results are mixed. Practice variability in terms of the content,
contexts and implementation of such interventions raises challenges in terms of
identifying an optimal arts programme model that could be adopted by other
service providers. Understanding how interventions may have the best chance at
broad implementation success and uptake is limited. METHODS/DESIGN: A realist
review will be undertaken. This aims to understand how visual arts interventions
influence outcomes in people living with dementia. The review will explore how
the context, that is the circumstances which enable or constrain, affect outcomes
through the activation of mechanisms. An early scoping search and a stakeholder
survey formulated the preliminary programme theory. A systematic literature
search across a broad range of disciplines (arts, humanities, social sciences,
health) will be undertaken to identify journal articles and grey literature. Data
will be extracted in relation to the programme theory, contextual factors,
mechanisms and outcomes and their configurations, background information about
the study design and participant characteristics, detail about the quantity
('dose') of an intervention, theoretical perspectives proposed by the authors of
the paper and further theorising by the reviewer. Thematic connections/patterns
will be sought across the extracted data, identifying patterns amongst contextual
factors, the mechanisms they trigger and the associated outcomes. DISCUSSION:
Along with stakeholder engagement and validation, this review will help inform
the development of an optimal, replicable arts intervention for people with
dementia as part of our broader research programme, titled 'Dementia and
Imagination' (funded by the Arts and Humanities Research Council). Forthcoming
work under this programme of research will test this theoretically informed
intervention in three different geographical areas of the UK. The production of
freely available practice guidance is a key aspect of dissemination. TRIAL
REGISTRATION: PROSPERO registration number CRD42014008702.
PMID- 25128287
TI - Trends and implications for achieving VISION 2020 human resources for eye health
targets in 16 countries of sub-Saharan Africa by the year 2020.
AB - BACKGROUND: Development of human resources for eye health (HReH) is a major
global eye health strategy to reduce the prevalence of avoidable visual
impairment by the year 2020. Building on our previous analysis of current
progress towards key HReH indicators and cataract surgery rates (CSRs), we
predicted future indicator achievement among 16 countries of sub-Saharan Africa
by 2020. METHODS: Surgical and HReH data were collected from national eye care
programme coordinators on six practitioner cadres: ophthalmologists, cataract
surgeons, ophthalmic clinical officers, ophthalmic nurses, optometrists and 'mid
level refractionists' and combined them with publicly available population data
to calculate practitioner-to-population ratios and CSRs. Data on workforce entry
and exit (2008 to 2010) was used to project practitioner population and CSR
growth between 2011 and 2020 in relation to projected growth in the general
population. Associations between indicator progress and the presence of a non
physician cataract surgeon cadre were also explored using Wilcoxon rank sum tests
and Spearman rank correlations. RESULTS: In our 16-country sample, practitioner
per million population ratios are predicted to increase slightly for surgeons
(ophthalmologists/cataract surgeons, from 3.1 in 2011 to 3.4 in 2020) and
ophthalmic nurses/clinical officers (5.8 to 6.8) but remain low for
refractionists (including optometrists, at 3.6 in 2011 and 2020). Among countries
that have not already achieved target indicators, however, practitioner growth
will be insufficient for any additional countries to reach the surgeon and
refractionist targets by year 2020. Without further strategy change and
investment, even after 2020, surgeon growth is only expected to sufficiently
outpace general population growth to reach the target in one country. For nurses,
two additional countries will achieve the target while one will fall below it. In
2011, high surgeon practitioner ratios were associated with high CSR, regardless
of the type of surgeon employed. The cataract surgeon workforce is growing
proportionately faster than the ophthalmologist. CONCLUSIONS: The HReH workforce
is not growing fast enough to achieve global eye health targets in most of the
sub-Saharan countries we surveyed by 2020. Countries seeking to make rapid
progress to improve CSR could prioritise investment in training new cataract
surgeons over ophthalmologists and improving surgical output efficiency.
PMID- 25128288
TI - Vitamin B12 deficiency with combined hematological and neuropsychiatric
derangements: a case report.
AB - INTRODUCTION: Although vitamin B12 deficiency is a well-known cause of
hematological and neuropsychiatric illness, the presentation of combined severe
pancytopenia, demyelination and prominent psychiatric impairment is rare. CASE
PRESENTATION: We present a case of a previously healthy 55-year-old East African
man with severe vitamin B12 deficiency (serum vitamin B12 22pmol/L) secondary to
pernicious anemia. He had a severe hypoproliferative megaloblastic anemia with
hemolysis (hemoglobin 61g/L, mean corpuscular volume 99fL, reticulocytes 0.8%,
haptoglobin undetectable), leukopenia (2.7*109/L), thrombocytopenia (96*109/L),
ataxia with central demyelination, and megaloblastic madness. The patient's
anemia, myelopathy and psychiatric condition responded well to parenteral vitamin
B12 replacement therapy, with significant improvement seen within weeks.
CONCLUSION: Hematological manifestations of vitamin B12 deficiency are typically
inversely correlated with the presence and severity of neuropsychiatric
impairment. Although uncommon, a presentation with severe hematological and
neuropsychiatric disease can occur, as illustrated by this case. Its presence may
help guide diagnosis as well as provide clinically important prognostic
information.
PMID- 25128289
TI - Patch-testing for the management of hypersensitivity reactions to second-line
anti-tuberculosis drugs: a case report.
AB - BACKGROUND: The second-line anti-tuberculosis drugs used in the treatment of
multidrug-resistant tuberculosis often cause adverse events, especially in
patients co-infected with the human immunodeficiency virus. Severe
hypersensitivity reactions due to these drugs are rare and there is little
published experience to guide their management. CASE PRESENTATION: A 17-year old
Indian female multidrug-resistant tuberculosis patient co-infected with human
immunodeficiency virus developed a hypersensitivity reaction after starting
second-line anti-tuberculosis treatment in Mumbai, India. The patient was being
treated with kanamycin, moxifloxacin, para-aminosalicylic acid, cycloserine,
clofazimine, and amoxicillin-clavulanic acid. Twenty-four hours later, the
patient developed generalized urticaria, morbilliform rash and fever. All drugs
were suspended and the patient was hospitalised for acute management. Skin patch
testing was used to identify drugs that potentially caused the hypersensitivity
reaction; results showed a strong reaction to clofazimine, moderate reaction to
kanamycin and mild reaction to cycloserine. An interim second-line anti
tuberculosis regimen was prescribed; cycloserine and kanamycin were then re
challenged one-by-one using incremental dosing, an approach that allowed
clinicians to re-introduce these drugs promptly and safely. The patient is
currently doing well. CONCLUSIONS: This is the first case-report of a multidrug
resistant tuberculosis patient co-infected with the human immunodeficiency virus
with hypersensitivity reaction to multiple second-line anti-tuberculosis drugs.
Skin patch-testing and controlled re-challenge can be a useful management
strategy in such patients. There is an urgent need for second-line anti
tuberculosis regimens that are more effective, safe and better tolerated.
PMID- 25128290
TI - Cultural differences in postnatal quality of life among German-speaking women - a
prospective survey in two countries.
AB - BACKGROUND: Assessment of quality of life after childbirth is an important health
outcome measurement for new mothers and is of special interest in midwifery. The
Mother-Generated Index (MGI) is a validated instrument to assess postnatal
quality of life. The tool has not been applied for making a cross-cultural
comparison before. This study investigated (a) responses to the MGI in German
speaking women in Germany and Switzerland; and (b) associations between MGI
scores on the one hand and maternity and midwifery care on the other. METHODS: A
two-stage survey was conducted in two rural hospitals 10 km apart, on opposite
sides of the German-Swiss border. The questionnaires included the MGI and
questions on socio-demographics, physical and mental health and maternity care,
and were distributed during the first days after birth and six weeks postpartum.
Parametric and non-parametric tests were computed with the statistical programme
SPSS. RESULTS: A total of 129 questionnaires were returned an average of three
days after birth and 83 in the follow-up after seven weeks. There were no
statistically significant differences in the MGI scores between the German and
the Swiss women (p = 0.22). Significantly more favourable MGI scores were found
associated with more adequate information during pregnancy (p = 0.02), a more
satisfactory birth experience (p < .01), epidural anaesthesia (p < 0.01), more
information (p = 0.01) and better support (p = 0.02) during the time in hospital
and less disturbed sleep (p < 0.01). Significantly lower MGI scores were
associated with the presence of a private doctor during birth (p = 0.01) and with
exclusive breastfeeding during the first postnatal days (p = 0.04). CONCLUSION:
The MGI scores of these German-speaking women were higher than those in other
studies reported previously. Thus the tool may be able to detect differences in
postnatal quality of life among women with substantially divergent cultural
backgrounds. Shortcomings in maternity and midwifery care were detected, as for
example the inadequate provision of information during pregnancy, a lack of
individualised postpartum care during the hospital stay and insufficient support
for exclusively breastfeeding mothers. The MGI is an appropriate instrument for
maternity care outcome measurement in cross-cultural comparison research.
PMID- 25128291
TI - Nitrogen limitation and high density responses in rice suggest a role for
ethylene under high density stress.
AB - BACKGROUND: High density stress, also known as intraspecies competition, causes
significant yield losses in a wide variety of crop plants. At the same time,
increases in density tolerance through selective breeding and the concomitant
ability to plant crops at a higher population density has been one of the most
important factors in the development of high yielding modern cultivars. RESULTS:
Physiological changes underlying high density stress were examined in Oryza
sativa plants over the course of a life cycle by assessing differences in gene
expression and metabolism. Moreover, the nitrogen limitation was examined in
parallel with high density stress to gain a better understanding of physiological
responses specific to high density stress. While both nitrogen limitation and
high density resulted in decreased shoot fresh weight, tiller number, plant
height and chlorophyll content, high density stress alone had a greater impact on
physiological factors. Decreases in aspartate and glutamate concentration were
found in plants grown under both stress conditions; however, high density stress
had a more significant effect on the concentration of these amino acids. Global
transcriptome analysis revealed a large proportion of genes with altered
expression in response to both stresses. The presence of ethylene-associated
genes in a majority of density responsive genes was investigated further.
Expression of ethylene biosynthesis genes ACC synthase 1, ACC synthase 2 and ACC
oxidase 7 were found to be upregulated in plants under high density stress.
Plants at high density were also found to up regulate ethylene-associated genes
and senescence genes, while cytokinin response and biosynthesis genes were down
regulated, consistent with higher ethylene production. CONCLUSIONS: High density
stress has similar but greater impact on plant growth and development compared to
nitrogen limitation. Global transcriptome changes implicate ethylene as a
volatile signal used to communicate proximity in under dense population growth
condition and suggest a role for phytohormones in high density stress response in
rice plants.
PMID- 25128293
TI - Role of statherin in oral carcinogenesis.
PMID- 25128292
TI - A biomechanical cause of low power production during FES cycling of subjects with
SCI.
AB - BACKGROUND: The goal of Functional Electrical Stimulation (FES) cycling is to
provide the health benefits of exercise to persons with paralysis. To achieve the
greatest health advantages, patients should produce the highest possible
mechanical power. However, the mechanical power output (PO) produced during FES
cycling is very low. Unfavorable biomechanics is one of the important factors
reducing PO. The purpose of this study was to investigate the primary joints and
muscles responsible for power generation and the role of antagonistic co
contraction in FES cycling. METHODS: Sixteen subjects with complete spinal cord
injury (SCI) pedaled a stationary recumbent FES tricycle at 60 rpm and a workload
of 15 W per leg, while pedal forces and crank angle were recorded. The joint
muscle moments, power and work were calculated using inverse dynamics equations.
RESULTS: Two characteristic patterns were found; in 12 subjects most work was
generated by the knee extensors in the propulsion phase (83% of total work),
while in 4 subjects most work was shared between by the knee extensors (42%) and
flexors (44%), respectively during propulsive and recovery phases. Hip extensors
produced only low net work (12 & 7%). For both patterns, extra concentric work
was necessary to overcome considerable eccentric work (-82 & -96%). CONCLUSIONS:
The primary power sources were the knee extensors of the quadriceps and the knee
flexors of the hamstrings. The antagonistic activity was generally low in
subjects with SCI because of the weakness of the hamstrings (compared to
quadriceps) and the superficial and insufficient hamstring mass activation with
FES.
PMID- 25128294
TI - Incorporation of salivary metabolomics in oral cancer diagnostics.
PMID- 25128295
TI - RAGE, inflammation and oral cancer: recreating the connexion.
PMID- 25128296
TI - Influence of a prudent diet on circulating cathepsin S in humans.
AB - BACKGROUND: Increased circulating cathepsin S levels have been linked to
increased risk of cardiometabolic diseases and cancer. However, whether cathepsin
S is a modifiable risk factor is unclear. We aimed to investigate the effects of
a prudent diet on plasma cathepsin S levels in healthy individuals. FINDINGS:
Explorative analyses of a randomized study were performed in 88 normal to
slightly overweight and hyperlipidemic men and women (aged 25 to 65) that were
randomly assigned to ad libitum prudent diet, i.e. healthy Nordic diet (ND) or a
control group (habitual Western diet) for 6 weeks. Whereas all foods in the ND
were provided, the control group was advised to consume their habitual diet
throughout the study. The ND was in line with dietary recommendations, e.g. low
in saturated fats, sugars and salt, but high in plant-based foods rich in fibre
and unsaturated fats.The ND significantly decreased cathepsin S levels (from 20.1
(+/-4.0 SD) to 19.7 MUg/L (+/-4.3 SD)) compared with control group (from 18.2 (+/
2.9 SD) to 19.1 MUg/L (+/-3.8 SD)). This difference remained after adjusting for
sex and change in insulin sensitivity (P = 0.03), and near significant after
adjusting for baseline cathepsin S levels (P = 0.06), but not for change in
weight or LDL-C. Changes in cathepsin S levels were directly correlated with
change in LDL-C. CONCLUSIONS: Compared with a habitual control diet, a provided
ad libitum healthy Nordic diet decreased cathepsin S levels in healthy
individuals, possibly mediated by weight loss or lowered LDL-C. These differences
between groups in cathepsin S were however not robust and therefore need further
investigation.
PMID- 25128297
TI - Efficacy of Bacillus thuringiensis var. israelensis against malaria mosquitoes in
northwestern Burkina Faso.
AB - BACKGROUND: In Sub Saharan Africa malaria remains one of the major health
problems and its control represents an important public health measure.
Integrated malaria control comprises the use of impregnated mosquito nets and
indoor residual spraying. The use of drugs to treat patients can create
additional pressure on the equation of malaria transmission. Vector control may
target the adult mosquitoes or their aquatic larval stages. Biological larvicides
such as Bacillus thuringiensis israelensis (Bti) represent a promising approach
to support malaria control programs by creating additional pressure on the
equation of malaria transmission. METHODS: In this study we examined the efficacy
of a water-dispersible granule formulation (WDG) of the biological larvicide Bti
(VectoBac(r)) against wild Anopheles spp. larvae. Different concentrations of the
larvicide were tested in standardized plastic tubs in the field against untreated
controls. In weekly intervals tubs were treated with fixed concentrations of
larvicide and the percentage reduction of larvae and pupae was calculated.
RESULTS: All used concentrations successfully killed 100 percent of the larvae
within 24 hours, while the higher concentrations showed a slightly prolonged
residual effect. Natural reconolization of larvae took place after two and three
days respectively, late instar larvae were not found before 5 days after
treatment. For the higher concentrations, up to three days no new larvae were
found, implicating that the residual effect of WDG in tropical conditions is
approximately one to two days. The overall pupae reduction in treated tubs was
98.5%. CONCLUSIONS: Biological larviciding with Bti can be a promising,
additional tool in the fight against malaria in Africa. Environmental
particularities in tropical Africa, first and foremost the rapid development of
mosquitoes from oviposition to imago have to be taken into account before
implementing such counter measures in national or international vector control
programs. Nonetheless biological larviciding seems to be an appropriate measure
for selected conditions, offering a significant contribution to the future of
malaria control.
PMID- 25128298
TI - Comparative study on the suitability of two techniques for measuring the transfer
of lipophilic drug models from lipid nanoparticles to lipophilic acceptors.
AB - Due to their particle size in the submicrometer range, lipid nanoparticles are
suitable for parenteral administration. In order to obtain information on their
potential in vivo performance, a simple and effective in vitro assay to evaluate
the drug release behavior of such particles is required. This study compares the
use of different experimental setups for this purpose. Lipid nanoparticles from
trimyristin which were loaded with fluorescent lipophilic drug models (a
temoporfin and Nile red) were used as donor particles. The transfer of the two
drug models to multilamellar vesicles (MLV) and emulsion droplets as lipophilic
acceptor compartments was examined. The determination of the transferred
substance was performed either after separation by centrifugation or by an in
situ flow cytometric technique. The transfer of temoporfin was slow to the
acceptor MLV and very rapid to the acceptor emulsion. With both acceptors, the
transfer of temoporfin stopped at a concentration much lower than the theoretical
equilibrium values. The transfer of the less lipophilic drug Nile red was very
rapid to both acceptors with equilibrium concentrations close to the expected
values. The transfer results of temoporfin especially to the acceptor MLV
obtained with the two detection techniques were comparable while the
centrifugation technique indicated an apparently higher Nile red transfer rate
than the flow cytometric technique. Both techniques are equally suitable to study
the transfer of temoporfin, while the flow cytometric technique is advantageous
to measure the very rapid transfer of Nile red.
PMID- 25128299
TI - Alpha-fetoprotein level as a biomarker of liver fibrosis status: a cross
sectional study of 619 consecutive patients with chronic hepatitis B.
AB - BACKGROUND: Hepatitis B virus (HBV) infection is a serious public health problem
worldwide. This study aimed to investigate the relationship between serum alpha
fetoprotein (AFP) levels and pathological stages of liver biopsy in patients with
chronic hepatitis B (CHB). METHODS: The study included 619 patients who were
diagnosed with CHB from March 2005 to December 2011. AFP levels were measured by
electrochemiluminescence. Liver biopsy samples were classified into five levels
of inflammation (G) and fibrosis (S) stages, according to the Chinese guidelines
for prevention and treatment of viral hepatitis. Two multivariable ordinal
regression models were performed to determine associations between AFP, GGT, and
APRI (AST/PLT ratio) and stages of inflammation and fibrosis. RESULTS:
Significant positive and moderate correlations were shown between AFP levels and
inflammation stages and between AFP levels and fibrosis stages (rho = 0.436 and
0.404, p < 0.001). Median values of AFP at liver fibrosis stages S0-1, S2, S3,
and S4 were 3.0, 3.4, 5.4, and 11.3 ng/ml, respectively, and median APRI (AST/PLT
ratio) was 0.41. Receiver operating characteristic (ROC) curve analyses revealed
that the areas under the curves (AUCs) were 0.685, 0.727, and 0.755 (all p
<0.001) for judging inflammation stages of G >= 2, G >= 3, G = 4 by AFP; and
0.691, 0.717, and 0.718 (all p <0.001) for judging fibrosis stages of S >= 2, S
>= 3, and S = 4 by AFP. APRI levels showed significant positive and moderate
correlations with inflammation stages (rho = 0.445, p < 0.001). AST, GGT, and
APRI levels showed significant positive but very weak to weak correlations with
fibrosis stages (rho = 0.137, 0.237, 0.281, p < 0.001). CONCLUSIONS: Serum AFP
levels increased as pathological levels of inflammation and fibrosis increased in
CHB patients. Our data showed the clinical significance of serum AFP levels in
diagnosing liver inflammation and fibrosis. Assessment of liver pathology may be
improved by creating a predictive mathematical model by which AFP levels with
other biomarkers.
PMID- 25128302
TI - An Indian eye to personalized medicine.
AB - Acknowledging the successful sequencing of the human genome and the valuable
insights it has rendered, genetic drafting of non-human organisms can further
enhance the understanding of modern biology. The price of sequencing technology
has plummeted with time, and there is a noticeable enhancement in its
implementation and recurrent usage. Sequenced genome information can be contained
in a microarray chip, and then processed by a computer system for inferring
analytics and predictions. Specifically, smart cards have been significantly
applicable to assimilate and retrieve complex data, with ease and implicit
mobility. Herein, we propose "The G-Card", a development with respect to the
prevalent smart card, and an extension to the Electronic Health Record (EHR),
that will hold the genome sequence of an individual, so that the medical
practitioner can better investigate irregularities in a patient's health and
hence recommend a precise prognosis.
PMID- 25128301
TI - Evaluation of respondent-driven sampling in a study of urban young men who have
sex with men.
AB - Evidence suggests that respondent-driven sampling (RDS) is an efficient approach
to sampling among varied populations of adult men who have sex with men (MSM)
both in the USA and abroad, although no studies have yet evaluated its
performance among younger MSM, a population with a steep rise in HIV infection in
recent years. Young MSM (YMSM) may differ in terms of their connectedness to
other YMSM (e.g., due to evolving sexual identity, internalization of sexual
minority stigma, and lack of disclosure to others) and mobility (e.g., due to
parental monitoring) which may inhibit the sampling process. The aims of this
study were to evaluate the efficiency and effectiveness of RDS-based sampling
among young urban MSM and to identify factors associated with recruitment
success. We hypothesized that demographic, social, behavioral, and network
factors, including racial/ethnic minority status, homelessness (i.e., as an
indicator of socioeconomic marginalization), HIV-positive status, substance use
problems, gay community connectedness, and network size would be positively
related to recruitment productivity, while sexual minority stigmatization,
environmental barriers (e.g., parental monitoring), and meeting sex partners on
the internet (i.e., virtual venue) would be negatively related to recruitment
productivity. Between December 2009 and February 2013, we used RDS to recruit a
sample of 450 YMSM, ages 16-20. Findings suggest that the use of RDS for sampling
among YMSM is challenging and may not be feasible based on the slow pace of
recruitment and low recruitment productivity. A large number of seeds (38 % of
the sample, n = 172) had to be added to the sample to maintain a reasonable pace
of recruitment, which makes use of the sample for RDS-based population estimates
questionable. In addition, the prevalence of short recruitment chains and
segmentation in patterns of recruitment by race/ethnicity further hamper the
network recruitment process. Thus, RDS was not particularly efficient in terms of
the rate of recruitment or effective in generating a representative sample.
Hypotheses regarding factors associated with recruitment success were supported
for network size and internalized stigma (but not other factors), suggesting that
participants with larger network sizes or high levels of internalized stigma may
have more and less success recruiting others, respectively.
PMID- 25128300
TI - The biography of the immune system and the control of cancer: from St Peregrine
to contemporary vaccination strategies.
AB - BACKGROUND: The historical basis and contemporary evidence for the use of immune
strategies for prevention of malignancies are reviewed. Emphasis is focussed on
the Febrile Infections and Melanoma (FEBIM) study on melanoma and on malignancies
that seem to be related to an overexpression of human endogenous retrovirus K
(HERV-K). DISCUSSION: It is claimed that, as a result of recent observational
studies, measures for prevention of some malignancies such as melanoma and
certain forms of leukaemia are already at hand: vaccination with Bacille Calmette
Guerin (BCG) of new-borns and vaccination with the yellow fever 17D (YFV) vaccine
of adults. While the evidence of their benefit for prevention of malignancies
requires substantiation, the observations that vaccinations with BCG and/or
vaccinia early in life improved the outcome of patients after surgical therapy of
melanoma are of practical relevance as the survival advantage conferred by prior
vaccination is greater than any contemporary adjuvant therapy. SUMMARY: The
reviewed findings open a debate as to whether controlled vaccination studies
should be conducted in patients and/or regions for whom/where they are needed
most urgently. A study proposal is made and discussed. If protection is
confirmed, the development of novel recombinant vaccines with wider ranges of
protection based, most likely, on BCG, YFV or vaccinia, could be attempted.
PMID- 25128303
TI - Management of Composite Tissue Defect of the Midfoot With a Free Anterolateral
Thigh Flap and Iliac Bone Graft: A Case Report.
AB - Composite tissue defects of the midfoot with extensive bone and soft tissue loss
represent a unique challenge because they can lead to primary amputation if not
reconstructed. One should repair both the bone structure and the soft tissue to
obtain satisfactory foot function for basic daily activities. In the present
study, we report on a case in which we successfully reconstructed an extensive
midfoot defect with iliac bone grafts for metatarsal reconstruction and an
anterolateral thigh flap for soft tissue coverage. This technique is a safe,
reliable, and functional method, offering single-stage reconstruction compared
with other microsurgical techniques used for such defects.
PMID- 25128304
TI - A Meta-Analysis for Postoperative Complications in Tibial Plafond Fracture: Open
Reduction and Internal Fixation Versus Limited Internal Fixation Combined With
External Fixator.
AB - The treatment of tibial plafond fractures is challenging to foot and ankle
surgeons. Open reduction and internal fixation and limited internal fixation
combined with an external fixator are 2 of the most commonly used methods of
tibial plafond fracture repair. However, conclusions regarding the superior
choice remain controversial. The present meta-analysis aimed to quantitatively
compare the postoperative complications between open reduction and internal
fixation and limited internal fixation combined with an external fixator for
tibial plafond fractures. Nine studies with 498 fractures in 494 patients were
included in the present study. The meta-analysis found no significant differences
in bone healing complications (risk ratio [RR] 1.17, 95% confidence interval [CI]
0.68 to 2.01, p = .58], nonunion (RR 1.09, 95% CI 0.51 to 2.36, p = .82),
malunion or delayed union (RR 1.24, 95% CI 0.57 to 2.69, p = .59), superficial
(RR 1.56, 95% CI 0.43 to 5.61, p = .50) and deep (RR 1.89, 95% CI 0.62 to 5.80)
infections, arthritis symptoms (RR 1.20, 95% CI 0.92 to 1.58, p = .18), or
chronic osteomyelitis (RR 0.31, 95% CI 0.05 to 1.84, p = .20) between the 2
groups.
PMID- 25128305
TI - Self-reported quality of life and diabetic foot infections.
AB - Foot infections in patients with diabetes mellitus (DM) are serious complications
that can result in hospitalization, the need for amputation, and premature
mortality. To the best of our knowledge, no published studies have specifically
investigated the effect of diabetic foot infection (DFI) on patient quality of
life. The aim of the present study was to compare the self-reported assessments
of quality of life in patients hospitalized with DFIs with those from a group of
patients without foot infections. We evaluated a study group of 47 patients who
had been hospitalized with DFIs and a control group of 47 patients with DM who
did not have any complaints referable to their foot or ankle. The self-reported
outcomes were assessed using the Medical Outcomes Study short form 36-item health
survey (SF-36) and the Foot and Ankle Ability Measurement. Patients hospitalized
with DFIs had significantly reduced self-reported SF-36 scores in all 8 subscales
compared with the cohort of patients with DM without foot complaints. The SF-36
physical component and mental component scores were significantly reduced in
patients with DFIs, indicating a negative effect on overall health. Self-reported
lower extremity function was also negatively affected with significantly lower
Foot and Ankle Measurement activity of daily living and sports scores for
patients with DFI. The present study has demonstrated the profoundly negative
affect that moderate and severe DFIs have on self-reported quality of life,
affecting both physical and mental well-being and lower extremity function.
PMID- 25128306
TI - Bilateral Ankle and Subtalar Joint Fusion Secondary to Guillain Barre-Induced
Foot Drop.
AB - Guillain-Barre syndrome is a serious disorder that occurs when the body's immune
system mistakenly attacks the peripheral nervous system. This leads to nerve
inflammation and damage that can cause muscle weakness and/or paralysis,
including foot drop. Therapy ranges from supportive measures, such as physical
therapy, to surgical intervention. It appears from the published data that these
patients, generally, have been left to their own devices, because no known cure
is available, necessitating reliance on others for their daily activities and
ambulation. We present a unique surgical option, with a follow-up period of 24
months, in which bilateral subtalar and ankle fusion allowed unassisted
ambulation to a patient who might otherwise have never walked again.
PMID- 25128307
TI - Comparison of postinjection protocols after intratendinous Achilles platelet-rich
plasma injections: a cadaveric study.
AB - The purpose of the present investigation was to evaluate the distribution of
intratendinous injected platelet-rich plasma (PRP) after 15 minutes of prone
resting versus immediate manipulation simulating weightbearing. Ten cadaveric
lower limbs were injected under ultrasound guidance with PRP dyed with India blue
ink. The dyed PRP was injected into the mid-portion of the Achilles tendon, after
which 5 specimens were placed in the prone position for 15 minutes (simulating
rest) and the remaining 5 specimens were manipulated through 100 cycles of ankle
dorsiflexion and plantarflexion (simulating walking). Thereafter, the specimens
were dissected, and the distribution of the India blue dye was ascertained. In
the simulated rest group, every specimen showed dyed PRP in the Achilles tendon
and in the space between the paratenon and tendon. The median craniocaudal spread
of the PRP was 140 (range 125 to 190) mm. In 4 of the simulated rest tendons
(80%), the distribution of PRP extended across the entire transverse plane width
of the tendon. In the simulated motion group, every specimen showed dyed PRP
extending across the entire transverse plane width of the tendon and in the space
between the paratenon and tendon. The median craniocaudal spread was 135 (range
115 to 117) mm. No statistically significant difference was found in the amount
of craniocaudal spread between the simulated motion and rest groups. In
conclusion, it does not appear to matter whether the ankle has been moved through
its range of motion or maintained stationary during the first 15 minutes after
PRP injection into the mid-portion of the Achilles tendon. The precise meaning of
this information in the clinical realm remains to be discerned.
PMID- 25128308
TI - A retrospective study of two Lapidus groups, each with a different method of rail
application.
AB - To date, few studies discussing the use of rail external fixation for the Lapidus
procedure have presented acceptable complication rates. At least 1 study has
suggested the technique is not recommended for routine use with this procedure.
We present 2 methods of external fixation application and 2 protocols of early
postoperative weightbearing in 25 patients, with a marked decrease in
complication rates from previously published studies. A retrospective study of 25
patients (within 2 patient groups) was performed, with a mean follow-up of 20
(range 12 to 38) months. Age, sex, incidence of fusion, interval to fusion,
weightbearing status, and complication rates were evaluated. All subjects
underwent Lapidus bunionectomy with joint preparation using sagittal planning.
The fusion sites for group A fixation included a medially placed external
fixation rail. Group B fixation included an interfragmentary screw and dorsal
rail placement. Weightbearing was allowed in group A on day 1 and in group B on
day 14. Our patient population consisted of 19 females (76%) and 6 males (24%).
The mean patient age was 45.6 (range 28 to 63) years. The overall incidence of
fusion was 96% (24 of 25), with complete union, although 1 patient's union was
delayed. The mean interval to union for group A was 7.6 (range 6 to 8) weeks and
for group B, was 9 (range 8 to 13) weeks. The primary complication encountered
was pin tract infection in 11 patients (44%). The use of rail external fixation
for Lapidus bunionectomy using either of the outlined techniques resulted in
significant reduction of previously reported complication rates and allowed for
early weightbearing.
PMID- 25128309
TI - Infectious Spondylodiscitis, Epidural Phlegmon, and Psoas Abscess Complicating
Diabetic Foot Infection: A Case Report.
AB - Few published case reports have cited vertebral osteomyelitis as a sequela of a
diabetic foot infection. The purpose of the present report is to increase
awareness of a potentially severe complication of diabetic foot ulceration:
vertebral osteomyelitis and associated pathologic features. We present the case
of a 63-year-old male with right calcaneal osteomyelitis who developed acute
onset lower back pain with concomitant fever and chills. Magnetic resonance
imaging revealed L4-L5 vertebral osteomyelitis, a T9-L1 epidural abscess, and a
right psoas muscle abscess secondary to hematogenous seeding from the calcaneus.
The patient underwent right partial calcanectomy, spinal and right psoas abscess
incision and drainage, and direct lumbar interbody fusion of L4-L5 with a right
iliac crest allograft. All bone, blood, and abscess cultures were positive for
methicillin-resistant Staphylococcus aureus. After the surgery, the patient's
pain resolved in his back and hip and he regained full right lower extremity
function. The 1-year follow-up examination revealed that the patient had
vertebral arthritis but was able to perform his activities of daily living with a
walker and cane. It is important to recognize the potential complications of
diabetic foot ulcerations and be aware of the identifying symptoms and treatment
options for this condition to prevent significant morbidity and mortality.
PMID- 25128310
TI - Two different treatment options for intramuscular plantar hemangioma: surgery
versus percutaneous sclerotherapy.
AB - Intramuscular hemangiomas are benign neoplasms usually seen in children and
adolescents. They tend to occur in the deep fascia and muscle and more often in
the lower extremity, although they are rarely encountered in the plantar
musculature. Surgical excision, ultrasound- or fluoroscopic-guided percutaneous
sclerotherapy, and angiographic embolization are all treatment options. Surgical
excision is the most prevalent form of therapy, although this can be difficult in
the hands and feet. For this reason, ultrasound- and fluoroscopic-guided
percutaneous sclerotherapy is a useful treatment option for pedal intramuscular
hemangioma. In the present report, we describe 2 cases of intramuscular
hemangioma in children, 1 treated by excision and 1 by percutaneous sclerosis.
PMID- 25128311
TI - Management of Idiopathic Clubfoot by Ponseti Technique in Children Presenting
After One Year of Age.
AB - We conducted a study to determine the effectiveness of the Ponseti technique in
the management of idiopathic congenital clubfoot in patients older than 1 year of
age. A total of 19 patients with 28 clubfeet (16 males [84.2%], 3 females
[15.8%]) were included in the present study. The mean age at presentation was 2.7
(range 1 to 3.5) years. The results of treatment using the Ponseti technique were
evaluated using the Pirani and Dimeglio scoring systems. The mean precorrection
total Pirani score was 4.84 (range 3.5 to 5.5) and the mean precorrection
Dimeglio score was 12.96 (range 10 to 14). The mean postcorrection total Pirani
score was 0.55 (range 0 to 1), and the mean postcorrection Dimeglio score was
2.32 (range 2 to 3). These differences were statistically significant (p < .001
and p < .001, respectively). In 92.8% of the feet, satisfactory correction of the
deformity was achieved. The mean number of casts applied was 8 (range 5 to 12).
All but 1 (3.6%) of the clubfeet required tenotomy to achieve correction. The
mean follow-up duration was 2.7 (range 1.5 to 3.5) years. We have concluded that
the Ponseti technique is an effective method for the management of idiopathic
congenital clubfoot, even in toddlers.
PMID- 25128312
TI - Tillaux fracture of the ankle in an adult: a rare injury.
AB - The Tillaux fracture of the ankle is an external rotation ankle injury resulting
in an avulsion fracture of the anterolateral tibial plafond. This injury is known
to occur in adolescents, although it has rarely been reported in adults. We
report a case of a Tillaux fracture in an adult. A brief description of the
history, mechanism of injury, required imaging, and treatment and other
management options are provided in the present report. Anatomic reduction, rigid
fixation, and early mobilization are emphasized to obtain a satisfactory
functional outcome, shown by the long-term follow-up findings.
PMID- 25128313
TI - Treatment of Calcaneal Fracture With Severe Soft Tissue Injury and Osteomyelitis:
A Case Report.
AB - Advancements in surgical technique have resulted in the ability to reconstruct
lower extremity injuries that would have previously been treated by amputation.
Currently, a paucity of data is available specifically addressing limb amputation
versus reconstruction for calcaneal fractures with severe soft tissue compromise.
Reconstruction leaves the patient with their native limb; however, multiple
surgeries, infections, chronic pain, and a poor functional outcome are very real
possibilities. We present the case of a complex calcaneal fracture complicated by
soft tissue injury and osteomyelitis that highlights the importance of shared
decision-making between patient and surgeon when considering reconstruction
versus amputation. This case exemplifies the need for open communication
concerning the risks and benefits of treatment modalities while simultaneously
considering the patient's expectations and desired outcomes.
PMID- 25128314
TI - Application of the five stages of grief to diabetic limb loss and amputation.
AB - A potentially underappreciated member of the multidisciplinary approach to
diabetic limb salvage is that of psychiatry. Diabetic patients are more likely to
experience depression, and diabetic patients with depression are more likely to
undergo an amputation. Also, both diabetes and depression independently increase
the healthcare costs in the United States. The objective of the present
investigation was to increase knowledge among diabetic foot practitioners with
respect to psychiatric and other mental health patient-care issues, specifically
the potential application of the 5 stages of grief to diabetic limb loss and
amputation. We enlisted the assistance of a clinical professor from the
psychiatry department at our institution to review the 5 stages of grief, provide
context specific for application to diabetic limb loss, and offer clinically
relevant guidelines for surgeons to better understand and communicate with their
patients at each stage. The 5 stages reviewed were denial, anger, bargaining,
depression, and acceptance. We hope that the present review will increase the
body of knowledge with respect to relevant psychiatric issues and the diabetic
foot and provide a starting point for increased awareness with respect to this
important, yet underappreciated, aspect of patient care.
PMID- 25128315
TI - Symptomatic Osseous Abnormalities at the Posteromedial Tubercle of the Talus:
Magnetic Resonance Imaging Features.
AB - Osseous alterations adjacent to the posteromedial tubercle of the talus that lead
to posterior ankle impingement and their imaging findings have been much less
well described than alterations of the posterolateral tubercle. We present 5
cases of osseous abnormalities at the posteromedial tubercle of the talus
depicted on magnetic resonance imaging in subjects with chronic symptoms at this
location, with no history of local trauma, who had presented with posteromedial
mechanical pain and/or tarsal tunnel syndrome. The symptoms were related to
mechanical changes of the bony and soft tissue structures, leading to posterior
impingement, and to neurovascular bundle entrapment at the tarsal tunnel, leading
to tarsal tunnel syndrome.
PMID- 25128316
TI - Multiple interdigital neuromas: a retrospective study of 279 feet with 462
neuromas.
AB - Morton's neuroma is a common pathologic entity that, traditionally, was
considered to be an isolated tumor that rarely affected more than 1 interdigital
space. However, in recent years, multiple neuromas have become more common in our
day-to-day practice. The objective of the present study was to assess the
frequency with which Morton's neuroma appears in the different interdigital
spaces. A retrospective study was performed of 279 feet that had been surgically
treated for Morton's neuroma using a dorsal approach during a 9-year period (from
January 2003 to December 2011), with an ultrasound scan taken preoperatively and
histopathologic analysis performed afterward. From the 279 treated feet, 462
interdigital neuromas were surgically removed. Of the 279 feet, 97 (34.8%)
displayed isolated neuromas, and 182 (65.2%) were treated for multiple neuromas.
Regarding the neuromas that were treated as isolated lesions, 74.2% were located
in the third space. For the feet affected by multiple interdigital neuromas, 100%
had a neuroma in the third space and 98.9% in the second. The incidence of
multiple interdigital neuromas can be considered frequent. The assessment,
therefore, of interdigital neuromas of the foot should include, at a minimum, the
second and third interdigital spaces.
PMID- 25128317
TI - Effective connectivity at synaptic level in humans: a review and future
prospects.
AB - Correct knowledge of the effective connectivity at the synaptic level in humans
is a key prerequisite for increasing our understanding of the operation of the
human central nervous system. Unfortunately, none of the current ambitious
collaborative neuroscience projects pay enough attention to this topic and are
thus unable to completely relate the microlevel properties of the system to its
emergent macrolevel behaviors. In this review article, the problem of effective
connectivity at the synaptic level in humans is explained, existing and possible
computational approaches to fill explanatory gaps are reviewed, and the requisite
characteristics of these approaches are considered.
PMID- 25128319
TI - Crista egregia: a geometrical model of the crista ampullaris, a sensory surface
that detects head rotations.
AB - The crista ampullaris is the epithelium at the end of the semicircular canals in
the inner ear of vertebrates, which contains the sensory cells involved in the
transduction of the rotational head movements into neuronal activity. The crista
surface has the form of a saddle, or a pair of saddles separated by a crux,
depending on the species and the canal considered. In birds, it was described as
a catenoid by Landolt et al. (J Comp Neurol 159(2):257-287, doi:
10.1002/cne.901590207 , 1972). In the present work, we establish that this
particular form results from principles of invariance maximization and energy
minimization. The formulation of the invariance principle was inspired by
Takumida (Biol Sci Space 15(4):356-358, 2001). More precisely, we suppose that in
functional conditions, the equations of linear elasticity are valid, and we
assume that in a certain domain of the cupula, in proximity of the crista
surface, (1) the stress tensor of the deformed cupula is invariant under the
gradient of the pressure, (2) the dissipation of energy is minimum. Then, we
deduce that in this domain the crista surface is a minimal surface and that it
must be either a planar, or helicoidal Scherk surface, or a piece of catenoid,
which is the unique minimal surface of revolution. If we add the hypothesis that
the direction of invariance of the stress tensor is unique and that a bilateral
symmetry of the crista exists, only the catenoid subsists. This finding has
important consequences for further functional modeling of the role of the
vestibular system in head motion detection and spatial orientation.
PMID- 25128320
TI - Torque-stiffness-controlled dynamic walking with central pattern generators.
AB - Walking behavior is modulated by controlling joint torques in most existing
passivity-based bipeds. Controlled Passive Walking with adaptable stiffness
exhibits controllable natural motions and energy efficient gaits. In this paper,
we propose torque-stiffness-controlled dynamic bipedal walking, which extends the
concept of Controlled Passive Walking by introducing structured control
parameters and a bio-inspired control method with central pattern generators. The
proposed walking paradigm is beneficial in clarifying the respective effects of
the external actuation and the internal natural dynamics. We present a seven-link
biped model to validate the presented walking. Effects of joint torque and joint
stiffness on gait selection, walking performance and walking pattern transitions
are studied in simulations. The work in this paper develops a new solution of
motion control of bipedal robots with adaptable stiffness and provides insights
of efficient and sophisticated walking gaits of humans.
PMID- 25128318
TI - Active inference, eye movements and oculomotor delays.
AB - This paper considers the problem of sensorimotor delays in the optimal control of
(smooth) eye movements under uncertainty. Specifically, we consider delays in the
visuo-oculomotor loop and their implications for active inference. Active
inference uses a generalisation of Kalman filtering to provide Bayes optimal
estimates of hidden states and action in generalised coordinates of motion.
Representing hidden states in generalised coordinates provides a simple way of
compensating for both sensory and oculomotor delays. The efficacy of this scheme
is illustrated using neuronal simulations of pursuit initiation responses, with
and without compensation. We then consider an extension of the generative model
to simulate smooth pursuit eye movements-in which the visuo-oculomotor system
believes both the target and its centre of gaze are attracted to a (hidden) point
moving in the visual field. Finally, the generative model is equipped with a
hierarchical structure, so that it can recognise and remember unseen (occluded)
trajectories and emit anticipatory responses. These simulations speak to a
straightforward and neurobiologically plausible solution to the generic problem
of integrating information from different sources with different temporal delays
and the particular difficulties encountered when a system-like the oculomotor
system-tries to control its environment with delayed signals.
PMID- 25128321
TI - Effect of display resolution on time to diagnosis with virtual pathology slides
in a systematic search task.
AB - Performing diagnoses using virtual slides can take pathologists significantly
longer than with glass slides, presenting a significant barrier to the use of
virtual slides in routine practice. Given the benefits in pathology workflow
efficiency and safety that virtual slides promise, it is important to understand
reasons for this difference and identify opportunities for improvement. The
effect of display resolution on time to diagnosis with virtual slides has not
previously been explored. The aim of this study was to assess the effect of
display resolution on time to diagnosis with virtual slides. Nine pathologists
participated in a counterbalanced crossover study, viewing axillary lymph node
slides on a microscope, a 23-in 2.3-megapixel single-screen display and a three
screen 11-megapixel display consisting of three 27-in displays. Time to diagnosis
and time to first target were faster on the microscope than on the single and
three-screen displays. There was no significant difference between the microscope
and the three-screen display in time to first target, while the time taken on the
single-screen display was significantly higher than that on the microscope. The
results suggest that a digital pathology workstation with an increased number of
pixels may make it easier to identify where cancer is located in the initial
slide overview, enabling quick location of diagnostically relevant regions of
interest. However, when a comprehensive, detailed search of a slide has to be
made, increased resolution may not offer any additional benefit.
PMID- 25128323
TI - Health needs and neighbourhood concerns of low income households vulnerable to
food insecurity.
PMID- 25128322
TI - Infusion of Gabralpha6 siRNA into the trigeminal ganglia increased the myogenic
orofacial nociceptive response of ovariectomized rats treated with 17beta
estradiol.
AB - High levels of 17beta-estradiol (E2) have been found to reduce inflammatory
temporomandibular joint (TMJ) pain. A search for genes effected by a high
concentration of estradiol showed an increase in GABAA receptor subunit alpha 6
(Gabralpha6) in the trigeminal ganglia (TG). Blockade of Gabralpha6 expression in
the TG increases masseter muscle nociception in male rats, but the relationship
between estradiol's effect on nociception and Gabralpha6 expression remains
unclear in females. To address this knowledge gap we hypothesized that reducing
Gabralpha6 expression in the TG will increase the orofacial nociceptive response
of ovariectomized female rats treated with estradiol. To administer hormone
osmotic pumps were placed in rats that dispensed a low diestrus plasma
concentration of 17beta-estradiol, in addition, 17beta-estradiol was injected to
produce a high proestrus plasma concentration of estradiol. A ligature was then
placed around the masseter tendon to induce a nociceptive response; a model for
TMJ muscle pain. Gabralpha6 small interfering RNA (siRNA) was later infused into
the TG and the nociceptive response was measured using von Frey filaments and a
meal duration assay. GABAA receptor expression was measured in the TG and
trigeminal nucleus caudalis and upper cervical region (Vc-C1). Ligature
significantly increased the nociceptive response but a high proestrus
concentration of 17beta-estradiol attenuated this response. Gabralpha6 siRNA
infusion decreased Gabralpha6 expression in the TG and Vc-C1 but increased the
nociceptive response after 17beta-estradiol treatment. The results suggest
estradiol decreased the orofacial nociceptive response, in part, by causing an
increase in Gabralpha6 expression.
PMID- 25128325
TI - Calcium in the heart: from physiology to disease.
AB - Contraction of the heart results from an increase of cytoplasmic Ca(2+)
concentration ([Ca(2+)]i), the so-called systolic Ca(2+) transient. Most of this
results from the release of Ca(2+) from the sarcoplasmic reticulum (SR) through
the ryanodine receptor (RyR). In turn, the amplitude of this Ca(2+) transient
determines the contractility of the heart. In this lecture, I consider the
factors which govern the size and stability of this Ca(2+) release. The amplitude
of the Ca(2+) transient is a steep function of SR Ca, resulting in a requirement
for very precise beat-to-beat regulation of SR Ca content. This is achieved by a
simple negative feedback mechanism, in which an increase of SR Ca content
increases the size of the Ca(2+) transient, resulting in a decrease of Ca(2+)
influx on the L-type Ca(2+) current and an increase of efflux through Na(+)
Ca(2+) exchange. Changing the activity of any of the Ca(2+)-cycling proteins will
change the steady-state SR Ca content. This feedback mechanism has many
consequences, including the fact that a change of RyR open probability has a only
a temporary effect on the amplitude of the Ca(2+) transient due to a compensating
change of SR Ca content. The remainder of the article considers the link between
intracellular Ca(2+) waves and arrhythmias. This is done in the context of
catecholaminergic polymorphic ventricular tachycardia, which is an inherited
arrhythmia syndrome, in many cases due to a RyR mutation, where arrhythmias occur
during exercise as a result of beta-adrenergic stimulation. Calcium waves occur
only when the SR Ca content exceeds a threshold level. Our data show that the
threshold is reduced by the RyR mutation and that the adrenergic stimulation
increases SR Ca content.
PMID- 25128324
TI - Prevention of diabetes and cardiovascular diseases in occupational health care:
feasibility and effectiveness.
AB - AIMS: To evaluate feasibility and effectiveness of lifestyle counseling in
occupational setting on decreasing risk for diabetes and cardiovascular disease.
METHODS: A health check-up including physical examination, blood tests,
questionnaires and health advice was completed on 2312 employees of an airline
company. Participants with elevated risk for type 2 diabetes based on FINDRISC
score and/or blood glucose measurement (n=657) were offered 1-3 additional
lifestyle counseling sessions and 53% of them agreed to participate. After 2.5
years, 1347 employees of 2199 invited participated in a follow-up study. RESULTS:
Among women and men with low baseline diabetes risk, cardiovascular risk factors
increased slightly during follow-up. Larger proportion of the men who attended
interventions lost weight at least 5% compared with the non-attendees (18.4% vs.
8.4%, p=0.031) and their FINDRISC score increased less (0.6 vs. 1.5, p=0.037).
Older age associated with participation in follow-up and higher baseline FINDRISC
score and presence of clinical and lifestyle risk factors and problems in sleep
and mood increased attendance in interventions. CONCLUSIONS: Identification of
employees with cardiovascular and diabetes risk, and the low intensity lifestyle
intervention were feasible in occupational health-care setting. However, the
health benefits were modest and observed only for men with increased risk.
PMID- 25128326
TI - Mitochondrial function/dysfunction in white adipose tissue.
AB - The role of mitochondria in white adipocytes has long been neglected due in part
to their lower abundance in these cells. However, accumulating evidence suggests
that mitochondria are vital for maintaining metabolic homeostasis in white
adipocytes because of their involvement in adipogenesis, fatty acid synthesis and
esterification, branched-chain amino acid catabolism and lipolysis. It is
therefore not surprising that white adipose tissue function can be perturbed by
altering mitochondrial components or oxidative capacity. Moreover, studies in
humans and animals with significantly altered fat mass, such as in obesity or
lipoatrophy, indicate that impaired mitochondrial function in adipocytes may be
linked directly to the development of metabolic diseases such as diabetes and
insulin resistance. However, recent studies that specifically targeted
mitochondrial function in adipocytes indicated dissociation between impaired
mitochondrial oxidative capacity and systemic insulin sensitivity.
PMID- 25128327
TI - Erythropoietin administration alone or in combination with endurance training
affects neither skeletal muscle morphology nor angiogenesis in healthy young men.
AB - The aim was to investigate the ability of an erythropoiesis-stimulating agent
(ESA), alone or in combination with endurance training, to induce changes in
human skeletal muscle fibre and vascular morphology. In a comparative study, 36
healthy untrained men were randomly dispersed into the following four groups:
sedentary-placebo (SP, n = 9); sedentary-ESA (SE, n = 9); training-placebo (TP, n
= 10); or training-ESA (TE, n = 8). The ESA or placebo was injected once weekly.
Training consisted of progressive bicycling three times per week for 10 weeks.
Before and after the intervention period, muscle biopsies and magnetic resonance
images were collected from the thigh muscles, blood was collected, body
composition measured and endurance exercise performance evaluated. The ESA
treatment (SE and TE) led to elevated haematocrit, and both ESA treatment and
training (SE, TP and TE) increased maximal O2 uptake. With regard to skeletal
muscle morphology, TP alone exhibited increases in whole-muscle cross-sectional
area and fibre diameter of all fibre types. Also exclusively for TP was an
increase in type IIa fibres and a corresponding decrease in type IIx fibres.
Furthermore, an overall training effect (TP and TE) was statistically
demonstrated in whole-muscle cross-sectional area, muscle fibre diameter and type
IIa and type IIx fibre distribution. With regard to muscle vascular morphology,
TP and TE both promoted a rise in capillary to muscle fibre ratio, with no
differences between the two groups. There were no effects of ESA treatment on any
of the muscle morphological parameters. Despite the haematopoietic effects of
ESA, we provide novel evidence that endurance training rather than ESA treatment
induces adaptational changes in angiogenesis and muscle morphology.
PMID- 25128328
TI - Desire thinking: what is it and what drives it?
AB - INTRODUCTION: The aim of this study was to provide an overview of the construct
of desire thinking and test a metacognitive model of desire thinking and craving,
based on the work of Spada, Caselli and Wells (2012; 2013), which aims to explain
the perseveration of desire thinking. METHOD: We conducted two studies involving
four clinical samples (total N = 493) and a community sample (N = 494) presenting
with different addictive behaviors. The relationships among variables were
examined by testing the fit of path models within each sample. RESULTS: In the
model presented it was proposed that positive metacognitions about desire
thinking are associated with, in turn, imaginal prefiguration and verbal
perseveration, marking the activation of desire thinking. Verbal perseveration is
then associated to negative metacognitions about desire thinking and craving
denoting the pathological escalation of desire thinking. Finally, a direct
association between positive metacognitions about desire thinking and negative
metacognitions about desire thinking would mark those occasions where target
achieving behaviour runs as an automatized schemata without the experience of
craving. Results indicated a good model fit in the clinical sample and a
variation in the model structure in the community sample. CONCLUSION: These
findings provide further support for the application of metacognitive theory to
desire thinking and craving in addictive behaviors.
PMID- 25128329
TI - OX26/CTX-conjugated PEGylated liposome as a dual-targeting gene delivery system
for brain glioma.
AB - BACKGROUND: The successful gene delivery into the brain is a major challenge due
to the presence of the blood-brain barrier (BBB). In order to transport plasmid
DNA across the BBB and target the brain glioma, the PEGylated liposomes (PLs)
modified with OX26 and chlorotoxin (CTX) were developed as a dual-targeting gene
delivery system, and the therapeutic efficacy of OX26/CTX-PL/pC27 against glioma
was evaluated using in vitro and in vivo experimental models. METHODS: The
PEGylated liposome complexes were prepared by the reverse phase evaporation
method, and their physicochemical properties were examined. The transfection
efficiency, intracellular distribution, in vitro effects of OX26/CTX-PL/pC27 were
determined on C6, F98 and HEK293T cell lines. The dual-targeting therapeutic
efficacy of OX26/CTX-PL/pC27 against glioma were assessed using the BMVECs/C6
cells co-culture model and the rat orthotopic glioma model. RESULTS: The OX26/CTX
PL/pDNA complexes exhibited a subglobose shape, and possessed notably low
toxicities to HEK293T and C6 cells post 4 h incubation. In the in vitro
transfection experiment, gene expressions of hTERTC27 from C6 and F98 cells were
significantly improved by OX26 and CTX modification. Our in vitro results also
showed that OX26 endowed the PLs with the transport ability across the BBB. Using
the BMVECs/C6 cells co-culture model, the viability of C6 cells was decreased to
46.0% after OX26/CTX-PL/pC27 transfection. The OX26/CTX-PL/pC27 complexes
exhibited enhanced therapeutic effects on C6 cells. Moreover, the dual-targeting
therapeutic effects were further conformed with diminished tumor volumes (18.81
+/- 6.15 mm3) and extended median survival time (46 days) in C6 glioma-bearing
rats. Immunohistochemical analysis revealed the therapeutic effects derived from
enhanced hTERTC27 expression in the tumor site. CONCLUSIONS: The PEGylated
liposomes modified with OX26 and CTX are able to significantly promote cell
transfection, increase the transport of plasmid DNA across the BBB and afterwards
target the brain glioma cells in vitro and in vivo, exhibit the most significant
therapeutic efficacy. The ligand OX26 plays a critical role in transporting the
lipoplexes across the BBB, and CTX acts as a major role in targeting brain glioma
cells. The results would encourage further developments for non-invasive
targeting therapy of brain gliomas by intravenous injection.
PMID- 25128330
TI - Examining the use of evidence-based and social media supported tools in freely
accessible physical activity intervention websites.
AB - BACKGROUND: It has been shown that physical activity is more likely to increase
if web-based interventions apply evidence-based components (e.g. self-monitoring)
and incorporate interactive social media applications (e.g. social networking),
but it is unclear to what extent these are being utilized in the publicly
available web-based physical activity interventions. The purpose of this study
was to evaluate whether freely accessible websites delivering physical activity
interventions use evidence-based behavior change techniques and provide social
media applications. METHODS: In 2013, a systematic search strategy examined 750
websites. Data was extracted on a wide range of variables (e.g. self-monitoring,
goal setting, and social media applications). To evaluate website quality a new
tool, comprising three sub-scores (Behavioral Components, Interactivity and User
Generated Content), was developed to assess implementation of behavior change
techniques and social media applications. An overall website quality scored was
obtained by summing the three sub-scores. RESULTS: Forty-six publicly available
websites were included in the study. The use of self-monitoring (54.3%), goal
setting (41.3%) and provision of feedback (46%) was relatively low given the
amount of evidence supporting these features. Whereas the presence of features
allowing users to generate content (73.9%), and social media components (Facebook
(65.2%), Twitter (47.8%), YouTube (48.7%), smartphone applications (34.8%)) was
relatively high considering their innovative and untested nature. Nearly all
websites applied some behavioral and social media applications. The average
Behavioral Components score was 3.45 (+/-2.53) out of 10. The average
Interactivity score was 3.57 (+/-2.16) out of 10. The average User Generated
Content Score was 4.02 (+/-2.77) out of 10. The average overall website quality
score was 11.04 (+/-6.92) out of 30. Four websites (8.7%) were classified as high
quality, 12 websites (26.1%) were classified as moderate quality, and 30 websites
(65.2%) were classified as low quality. CONCLUSIONS: Despite large developments
in Internet technology and growth in the knowledge of how to develop more
effective web-based interventions, overall website quality was low and the
majority of freely available physical activity websites lack the components
associated with behavior change. However, the results show that website quality
can be improved by taking a number of simple steps, and the presence of social
media applications in most websites is encouraging.
PMID- 25128331
TI - Open drug scenes: responses of five European cities.
AB - BACKGROUND: Open drug scenes are gatherings of drug users who publicly consume
and deal drugs. The authors conducted a study of five European cities that have
met such scenes constructively. The aim was to investigate shared and non-shared
interventions and strategies in order to increase the understanding of this type
of problem. METHODS: First a description was made for the cities of Amsterdam,
Frankfurt, Vienna, Zurich and Lisbon. These descriptions were sent to contact
persons in each city prior to visit by the researchers. The methods and
strategies in each city were discussed and core choices and efforts extracted. A
report was sent to the contact group for corrections and clarifications. The
paper analyses shared and non-shared traits and strategies. RESULTS: All of the
cities had initially a period with conflict between liberal and restrictive
policies. A political consensus seems to be a prerequisite for effective action.
A core shared characteristic was that drug dependence was met as a health problem
and drug use behaviour as a public nuisance problem. Low threshold health
services including opioid maintenance treatment were combined with outreach
social work and effective policing. CONCLUSION: Prevention, harm reduction and
treatment should be combined with law enforcement based on cooperation between
police, health care and social services. The aim should be "coexistence" between
society and users of illegal substances and the strategy based on several years
planning and conjoint efforts. The solutions are found in appropriate
combinations of harm reduction and restrictive measures.
PMID- 25128332
TI - Community engagement and knowledge translation: progress and challenge in autism
research.
AB - The last decade has seen significant growth in scientific understanding and
public awareness of autism. There is still a long road ahead before this
awareness can be matched with parallel improvements in evidence-based practice.
The process of translating evidence into community care has been hampered by the
seeming disconnect between the mainstream scientific research agenda and the
immediate priorities of many communities. The need for community engagement in
the process of translating knowledge into impact has been recognized. However,
there remains little consensus or empirical data regarding the process of such
engagement and how to measure its impact. We shed light on a number of engagement
models and tools, previously advocated in health research, as they apply to
autism research. Furthermore, we illustrate the utility of such tools in
supporting identification of knowledge gaps and priorities, using two community
based case studies. The case studies illustrate that information generated from
research is indeed relevant and critical for knowledge users in the community.
Simple and systematic methods can support the translation and uptake of knowledge
in diverse communities, therefore enhancing engagement with research and bridging
research findings with immediate community needs.
PMID- 25128333
TI - The pattern of hominin postcranial evolution reconsidered in light of size
related shape variation of the distal humerus.
AB - Previous research suggests that some hominin postcranial features do not follow a
linear path of increasing modernization through geological time. With respect to
the distal humerus, in particular, the earliest known hominin specimens are
reportedly among the most modern in morphology, while some later humeri appear
further removed from the average modern human shape. Although Plio-Pleistocene
humeri vary widely in size, previous studies have failed to account for size
related shape variation when making morphometric comparisons. This study
reexamines hominin postcranial evolution in light of distal humeral allometry.
Using two-dimensional landmark data, the relationship between specimen size and
shape among modern humans is quantified using multivariate regression and
principal components analysis of size-shape space. Fossils are compared with
modern human shapes expected at a given size, as well as with the overall average
human shape. The null hypothesis of humeral isometry in modern humans is
rejected. Subsequently, if one takes allometry into account, the apparent pattern
of hominin humeral evolution does not resemble the pattern described above. All
14 of the Plio-Pleistocene hominin fossils examined here share a similar pattern
of shape differences from equivalently-sized modern humans, though they vary in
the extent to which these differences are expressed. The oldest specimen in the
sample (KNM-KP 271; Australopithecus anamensis) exhibits the least human-like
elbow morphology. Similarly primitive morphology characterizes all younger
species of Australopithecus as well as Paranthropus robustus. After 2 Ma, a
subtly more human-like elbow morphology is apparent among specimens attributed to
early Homo, as well as among isolated specimens that may represent either Homo or
Paranthropus boisei. This study emphasizes the need to consider size-related
shape variation when individual fossil specimens are compared with the average
shape of a comparative group, particularly when specimens fall near an extreme of
the comparative size distribution.
PMID- 25128334
TI - A Leslie matrix model for Sicyopterus lagocephalus in La Reunion: sensitivity,
uncertainty and research prioritization.
AB - We propose a Leslie matrix model for the population dynamics of Sicyopterus
lagocephalus in La Reunion. In order to capture both the amphidromous and the
seasonal natures of the species' life history the model has four stages
(sea+three river sites) and is cyclical with a 12 month period. Baseline
parameters (age-specific fecundity, spatial dispersion patterns and survival
rates) were chosen in such a way that the dominant eigenvalue of the year-on-year
projection matrix is 1. Large uncertainties on the parameter values preclude the
use of the model for management purpose. A sensitivity/uncertainty analysis sheds
light on the parameters that cause much of the output to vary and that are poorly
known: the life expectancy in rivers and the mortality both at river mouths and
during the drift of larvae to sea. The aim is to help policymakers and
researchers prioritize data acquisition efforts. The ultimate goal is a
sustainable management of Sicyopterus lagocephalus in La Reunion.
PMID- 25128335
TI - Services for Enhanced Recovery with Intensive and Continued Engagement (SERWICE):
an outpatient psychiatric rehabilitation model from India.
PMID- 25128336
TI - Global Summit on Regulatory Science 2013.
AB - Regulatory science has been defined as the science that is used to develop
regulatory decisions by government bodies. Regulatory science encompasses many
scientific disciplines that oversee many studies producing a wide array of data.
These may include fundamental research into the cellular interaction or response
to a particular chemical or substance, hazard-assessment and dose-response
studies in animal species, neurophysiological or neurobehavioral studies, best
practices for the generation and analysis of genomics data, bioinformatics
approaches, and mathematical modeling of risk. The Global Summit on Regulatory
Science is an international conference with a mission to explore emerging and
innovative technologies, and provide a platform to enhance translation of basic
science into regulatory applications. The Third Global Summit on Regulatory
Science which focused on nanotechnology is discussed.
PMID- 25128337
TI - Site-directed mutagenesis of the heterotrimeric killer toxin zymocin identifies
residues required for early steps in toxin action.
AB - Zymocin is a Kluyveromyces lactis protein toxin composed of alphabetagamma
subunits encoded by the cytoplasmic virus-like element k1 and functions by
alphabeta-assisted delivery of the anticodon nuclease (ACNase) gamma into target
cells. The toxin binds to cells' chitin and exhibits chitinase activity in vitro
that might be important during gamma import. Saccharomyces cerevisiae strains
carrying k1-derived hybrid elements deficient in either alphabeta (k1ORF2) or
gamma (k1ORF4) were generated. Loss of either gene abrogates toxicity, and
unexpectedly, Orf2 secretion depends on Orf4 cosecretion. Functional zymocin
assembly can be restored by nuclear expression of k1ORF2 or k1ORF4, providing an
opportunity to conduct site-directed mutagenesis of holozymocin. Complementation
required active site residues of alpha's chitinase domain and the sole cysteine
residue of beta (Cys250). Since betagamma are reportedly disulfide linked, the
requirement for the conserved gamma C231 was probed. Toxicity of intracellularly
expressed gamma C231A indicated no major defect in ACNase activity, while
complementation of k1DeltaORF4 by gamma C231A was lost, consistent with a role of
beta C250 and gamma C231 in zymocin assembly. To test the capability of alphabeta
to carry alternative cargos, the heterologous ACNase from Pichia acaciae (P.
acaciae Orf2 [PaOrf2]) was expressed, along with its immunity gene, in
k1DeltaORF4. While efficient secretion of PaOrf2 was detected, suppression of the
k1DeltaORF4-derived k1Orf2 secretion defect was not observed. Thus, the
dependency of k1Orf2 on k1Orf4 cosecretion needs to be overcome prior to studying
alphabeta's capability to deliver other cargo proteins into target cells.
PMID- 25128338
TI - Engineering of Pseudomonas taiwanensis VLB120 for constitutive solvent tolerance
and increased specific styrene epoxidation activity.
AB - The application of whole cells as biocatalysts is often limited by the toxicity
of organic solvents, which constitute interesting substrates/products or can be
used as a second phase for in situ product removal and as tools to control
multistep biocatalysis. Solvent-tolerant bacteria, especially Pseudomonas
strains, are proposed as promising hosts to overcome such limitations due to
their inherent solvent tolerance mechanisms. However, potential industrial
applications suffer from tedious, unproductive adaptation processes, phenotypic
variability, and instable solvent-tolerant phenotypes. In this study, genes
described to be involved in solvent tolerance were identified in Pseudomonas
taiwanensis VLB120, and adaptive solvent tolerance was proven by cultivation in
the presence of 1% (vol/vol) toluene. Deletion of ttgV, coding for the specific
transcriptional repressor of solvent efflux pump TtgGHI gene expression, led to
constitutively solvent-tolerant mutants of P. taiwanensis VLB120 and
VLB120DeltaC. Interestingly, the increased amount of solvent efflux pumps
enhanced not only growth in the presence of toluene and styrene but also the
biocatalytic performance in terms of stereospecific styrene epoxidation, although
proton-driven solvent efflux is expected to compete with the styrene
monooxygenase for metabolic energy. Compared to that of the P. taiwanensis
VLB120DeltaC parent strain, the maximum specific epoxidation activity of P.
taiwanensis VLB120DeltaCDeltattgV doubled to 67 U/g of cells (dry weight). This
study shows that solvent tolerance mechanisms, e.g., the solvent efflux pump
TtgGHI, not only allow for growth in the presence of organic compounds but can
also be used as tools to improve redox biocatalysis involving organic solvents.
PMID- 25128339
TI - Silver resistance genes are overrepresented among Escherichia coli isolates with
CTX-M production.
AB - Members of the Enterobacteriaceae with extended-spectrum beta-lactamases (ESBLs)
of the CTX-M type have disseminated rapidly in recent years and have become a
threat to public health. In parallel with the CTX-M type expansion, the
consumption and widespread use of silver-containing products has increased. To
determine the carriage rates of silver resistance genes in different Escherichia
coli populations, the presence of three silver resistance genes (silE, silP, and
silS) and genes encoding CTX-M-, TEM-, and SHV-type enzymes were explored in E.
coli isolates of human (n = 105) and avian (n = 111) origin. The antibiotic
profiles were also determined. Isolates harboring CTX-M genes were further
characterized, and phenotypic silver resistance was examined. The silE gene was
present in 13 of the isolates. All of them were of human origin. Eleven of these
isolates harbored ESBLs of the CTX-M type (P = 0.007), and eight of them were
typed as CTX-M-15 and three as CTX-M-14. None of the silE-positive isolates was
related to the O25b-ST131 clone, but 10 out of 13 belonged to the ST10 or ST58
complexes. Phenotypic silver resistance (silver nitrate MIC > 512 mg/liter) was
observed after silver exposure in 12 of them, and a concomitant reduced
susceptibility to piperacillin-tazobactam developed in three. In conclusion, 12%
of the human E. coli isolates but none of the avian isolates harbored silver
resistance genes. This indicates another route for or level of silver exposure
for humans than that caused by common environmental contamination. Since silE
positive isolates were significantly more often found in CTX-M-positive isolates,
it is possible that silver may exert a selective pressure on CTX-M-producing E.
coli isolates.
PMID- 25128340
TI - Characterization of novel polycyclic aromatic hydrocarbon dioxygenases from the
bacterial metagenomic DNA of a contaminated soil.
AB - Ring-hydroxylating dioxygenases (RHDs) play a crucial role in the biodegradation
of a range of aromatic hydrocarbons found on polluted sites, including polycyclic
aromatic hydrocarbons (PAHs). Current knowledge on RHDs comes essentially from
studies on culturable bacterial strains, while compelling evidence indicates that
pollutant removal is mostly achieved by uncultured species. In this study, a
combination of DNA-SIP labeling and metagenomic sequence analysis was implemented
to investigate the metabolic potential of main PAH degraders on a polluted site.
Following in situ labeling using [(13)C]phenanthrene, the labeled metagenomic DNA
was isolated from soil and subjected to shotgun sequencing. Most annotated
sequences were predicted to belong to Betaproteobacteria, especially
Rhodocyclaceae and Burkholderiales, which is consistent with previous findings
showing that main PAH degraders on this site were affiliated to these taxa. Based
on metagenomic data, four RHD gene sets were amplified and cloned from soil DNA.
For each set, PCR yielded multiple amplicons with sequences differing by up to
321 nucleotides (17%), reflecting the great genetic diversity prevailing in soil.
RHDs were successfully overexpressed in Escherichia coli, but full activity
required the coexpression of two electron carrier genes, also cloned from soil
DNA. Remarkably, two RHDs exhibited much higher activity when associated with
electron carriers from a sphingomonad. The four RHDs showed markedly different
preferences for two- and three-ring PAHs but were poorly active on four-ring
PAHs. Three RHDs preferentially hydroxylated phenanthrene on the C-1 and C-2
positions rather than on the C-3 and C-4 positions, suggesting that degradation
occurred through an alternate pathway.
PMID- 25128341
TI - Surveillance of viruses in wild fish populations in areas around the Gulf of
Cadiz (South Atlantic Iberian Peninsula).
AB - This report describes a viral epidemiological study of wild fish around the Gulf
of Cadiz (southwestern Iberian Peninsula) and is focused on infectious pancreatic
necrosis virus (IPNV), viral hemorrhagic septicemia virus (VHSV), and viral
nervous necrosis virus (VNNV). One fish species (Chelon labrosus) was sampled
inside the gulf, at the mouth of the San Pedro River. Another 29 were sampled, in
three oceanographic campaigns, at sites around the Bay of Cadiz. The fish were
processed individually and subjected to isolation in cell culture and molecular
diagnosis. VHSV was not isolated from any species. Thirteen IPNV-type isolates
were obtained from barracuda (Sphyraena sphyraena), axillary seabream (Pagellus
acarne), common two-banded seabream (Diplodus vulgaris), common pandora (P.
erythrinus), Senegal seabream (D. bellottii), and surmullet (Mullus surmuletus).
Six VNNV isolates were obtained from axillary seabream, common pandora, black
seabream (Spondyliosoma cantharus), red mullet (Mullet barbatus), Lusitanian
toadfish (Halobatrachus didactylus), and tub gurnard (Chelidonichtys lucerna). In
the river mouth, viruses were detected only after reamplification, obtaining
prevalence percentages of IPNV and VNNV (44.4 and 63.0%, respectively) much
higher than those observed in the oceanographic campaigns (25.7 and 19.6%,
respectively). The opposite results were obtained in the case of VHSV after
reamplification: 11.1% in the river mouth and 43.6% in the oceanic locations.
Analyzing the results with respect to the proximity of the sampling sites to the
coast, an anthropogenic influence on wild fish is suggested and discussed. The
type of viruses and the presence of natural reassortants are also discussed.
PMID- 25128342
TI - Incorporation of exogenous fatty acids protects Enterococcus faecalis from
membrane-damaging agents.
AB - Enterococcus faecalis is a commensal bacterium of the mammalian intestine that
can persist in soil and aquatic systems and can be a nosocomial pathogen to
humans. It employs multiple stress adaptation strategies in order to survive such
a wide range of environments. Within this study, we sought to elucidate whether
membrane fatty acid composition changes are an important component for stress
adaptation. We noted that E. faecalis OG1RF was capable of changing its membrane
composition depending upon growth phase and temperature. The organism also
readily incorporated fatty acids from bile, serum, and medium supplemented with
individual fatty acids, often dramatically changing the membrane composition such
that a single fatty acid was predominant. Growth in either low levels of bile or
specific individual fatty acids was found to protect the organism from membrane
challenges such as high bile exposure. In particular, we observed that when grown
in low levels of bile, serum, or the host-derived fatty acids oleic acid and
linoleic acid, E. faecalis was better able to survive the antibiotic daptomycin.
Interestingly, the degree of membrane saturation did not appear to be important
for protection from the stressors examined here; instead, it appears that a
specific fatty acid or combination of fatty acids is critical for stress
resistance.
PMID- 25128343
TI - Analysis of the xplAB-containing gene cluster involved in the bacterial
degradation of the explosive hexahydro-1,3,5-trinitro-1,3,5-triazine.
AB - Repeated use of the explosive compound hexahydro-1,3,5-trinitro-1,3,5-triazine
(RDX) on military land has resulted in significant soil and groundwater
pollution. Rates of degradation of RDX in the environment are low, and
accumulated RDX, which the U.S. Environmental Protection Agency has determined is
a possible human carcinogen, is now threatening drinking water supplies. RDX
degrading microorganisms have been isolated from RDX-contaminated land; however,
despite the presence of these species in contaminated soils, RDX pollution
persists. To further understand this problem, we studied RDX-degrading species
belonging to four different genera (Rhodococcus, Microbacterium, Gordonia, and
Williamsia) isolated from geographically distinct locations and established that
the xplA and xplB (xplAB) genes, which encode a cytochrome P450 and a flavodoxin
redox partner, respectively, are nearly identical in all these species. Together,
the xplAB system catalyzes the reductive denitration of RDX and subsequent ring
cleavage under aerobic and anaerobic conditions. In addition to xplAB, the
Rhodococcus species studied here share a 14-kb region flanking xplAB; thus, it
appears likely that the RDX-metabolizing ability was transferred as a genomic
island within a transposable element. The conservation and transfer of xplAB
flanking genes suggest a role in RDX metabolism. We therefore independently
knocked out genes within this cluster in the RDX-degrading species Rhodococcus
rhodochrous 11Y. Analysis of the resulting mutants revealed that XplA is
essential for RDX degradation and that XplB is not the sole contributor of
reducing equivalents to XplA. While XplA expression is induced under nitrogen
limiting conditions and further enhanced by the presence of RDX, MarR is not
regulated by RDX.
PMID- 25128344
TI - Strain diversity of CTX-M-producing Enterobacteriaceae in individual pigs:
insights into the dynamics of shedding during the production cycle.
AB - The aim of this study was to evaluate the population dynamics of CTX-M-producing
Enterobacteriaceae in individual pigs on a farm positive for CTX-M-14-producing
Escherichia coli. Fecal samples were collected once around the farrowing time
from five sows and four times along the production cycle from two of their
respective offspring. Multiple colonies per sample were isolated on cefotaxime
supplemented MacConkey agar with or without prior enrichment, resulting in 98
isolates identified by matrix-assisted laser desorption ionization-time of flight
mass spectrometry and tested for blaCTX-M. CTX-M-positive isolates (n = 86) were
typed by pulsed-field gel electrophoresis (PFGE). Plasmids harboring blaCTX-M
were characterized in 22 representative isolates by replicon typing and
restriction fragment length polymorphism. Based on the PFGE results, all
individuals shed unrelated CTX-M-14-producing E. coli strains during the course
of life. Concomitant shedding of CTX-M-2/97-producing Proteus mirabilis or
Providencia rettgeri was observed in two sows and two offspring. At least two
genetically unrelated CTX-M-producing E. coli strains were isolated from
approximately one-fourth of the samples, with remarkable differences between
isolates obtained by enrichment and direct plating. A clear decrease in strain
diversity was observed after weaning. Dissemination of blaCTX-M-14 within the
farm was attributed to horizontal transfer of an IncK plasmid that did not carry
additional resistance genes and persisted in the absence of antimicrobial
selective pressure. Assessment of strain diversity was shown to be influenced by
the production stage from which samples were collected, as well as by the
isolation method, providing useful information for the design and interpretation
of future epidemiological studies of CTX-M-producing Enterobacteriaceae in pig
farms.
PMID- 25128345
TI - The two-component GacS-GacA system activates lipA translation by RsmE but not
RsmA in Pseudomonas protegens Pf-5.
AB - In Pseudomonas spp., the Gac-Rsm signal transduction system is required for the
production of lipases. The current model assumes that the system induces lipase
gene transcription mediated through the quorum-sensing (QS) system. However,
there are no reports of a QS system based upon N-acyl homoserine lactones or the
regulation of lipase gene expression in Pseudomonas protegens. In this study, we
investigated the regulatory mechanism acting on lipA expression activated by the
Gac-Rsm system in P. protegens Pf-5 through deletion and overexpression of gacA,
overexpression of rsmA or rsmE, expression of various lacZ fusions, reverse
transcription-PCR analysis, and determination of whole-cell lipase activity. The
results demonstrated that the GacS-GacA (GacS/A) system activates lipA expression
at both the transcriptional and the translational levels but that the
translational level is the key regulatory pathway. Further results showed that
the activation of lipA translation by the GacS/A system is mediated through RsmE,
which inhibits lipA translation by binding to the ACAAGGAUGU sequence overlapping
the Shine-Dalgarno (SD) sequence of lipA mRNA to hinder the access of the 30S
ribosomal subunit to the SD sequence. Moreover, the GacS/A system promotes lipA
transcription through the mediation of RsmA inhibiting lipA transcription via an
unknown pathway. Besides the transcriptional repression, RsmA mainly activates
lipA translation by negatively regulating rsmE translation. In summary, in P.
protegens Pf-5, the Gac-RsmE system mainly and directly activates lipA
translation and the Gac-RsmA system indirectly enhances lipA transcription.
PMID- 25128346
TI - Microbial odor profile of polyester and cotton clothes after a fitness session.
AB - Clothing textiles protect our human body against external factors. These textiles
are not sterile and can harbor high bacterial counts as sweat and bacteria are
transmitted from the skin. We investigated the microbial growth and odor
development in cotton and synthetic clothing fabrics. T-shirts were collected
from 26 healthy individuals after an intensive bicycle spinning session and
incubated for 28 h before analysis. A trained odor panel determined significant
differences between polyester versus cotton fabrics for the hedonic value, the
intensity, and five qualitative odor characteristics. The polyester T-shirts
smelled significantly less pleasant and more intense, compared to the cotton T
shirts. A dissimilar bacterial growth was found in cotton versus synthetic
clothing textiles. Micrococci were isolated in almost all synthetic shirts and
were detected almost solely on synthetic shirts by means of denaturing gradient
gel electrophoresis fingerprinting. A selective enrichment of micrococci in an in
vitro growth experiment confirmed the presence of these species on polyester.
Staphylococci were abundant on both cotton and synthetic fabrics. Corynebacteria
were not enriched on any textile type. This research found that the composition
of clothing fibers promotes differential growth of textile microbes and, as such,
determines possible malodor generation.
PMID- 25128348
TI - Is society being reshaped on a microbiological and epigenetic level by the way
women give birth?
PMID- 25128347
TI - Enhanced uranium immobilization and reduction by Geobacter sulfurreducens
biofilms.
AB - Biofilms formed by dissimilatory metal reducers are of interest to develop
permeable biobarriers for the immobilization of soluble contaminants such as
uranium. Here we show that biofilms of the model uranium-reducing bacterium
Geobacter sulfurreducens immobilized substantially more U(VI) than planktonic
cells and did so for longer periods of time, reductively precipitating it to a
mononuclear U(IV) phase involving carbon ligands. The biofilms also tolerated
high and otherwise toxic concentrations (up to 5 mM) of uranium, consistent with
a respiratory strategy that also protected the cells from uranium toxicity. The
enhanced ability of the biofilms to immobilize uranium correlated only partially
with the biofilm biomass and thickness and depended greatly on the area of the
biofilm exposed to the soluble contaminant. In contrast, uranium reduction
depended on the expression of Geobacter conductive pili and, to a lesser extent,
on the presence of the c cytochrome OmcZ in the biofilm matrix. The results
support a model in which the electroactive biofilm matrix immobilizes and reduces
the uranium in the top stratum. This mechanism prevents the permeation and
mineralization of uranium in the cell envelope, thereby preserving essential
cellular functions and enhancing the catalytic capacity of Geobacter cells to
reduce uranium. Hence, the biofilms provide cells with a physically and
chemically protected environment for the sustained immobilization and reduction
of uranium that is of interest for the development of improved strategies for the
in situ bioremediation of environments impacted by uranium contamination.
PMID- 25128350
TI - Safety and tolerability of zonisamide in paediatric patients with epilepsy.
AB - BACKGROUND: Zonisamide has recently been approved in Europe for the adjunctive
treatment of partial seizures (with or without secondary generalisation) in
adolescents and children aged >=6 years. AIM: To further assess the safety of
adjunctive zonisamide in paediatric epilepsy patients. METHODS: A pooled analysis
of data from 17 studies (including four randomised, double-blind trials) was
conducted. The safety population comprised patients aged <=16 years receiving at
least one dose of study drug. Assessments included treatment-emergent adverse
events (TEAEs), clinical laboratory parameters, vital signs and
electrocardiography. RESULTS: The analysis included 398 patients treated with
zonisamide (<12 years, n = 191; 12-16 years, n = 207). All but seven patients
received zonisamide as adjunctive therapy. Mean duration of exposure was 318.7
days (mean dose, 253.1 mg/day). Most TEAEs were of mild or moderate intensity.
The most frequently reported treatment-related TEAEs were decreased appetite
(15.6%), somnolence (12.1%), fatigue (9.3%), dizziness (6.0%), decreased weight
(5.8%), irritability (5.8%) and headache (5.3%). Incidence of serious zonisamide
related TEAEs was low (3.5% overall). TEAEs most commonly leading to
discontinuation were lethargy (1.0%) and fatigue (1.0%). TEAEs of decreased
weight and decreased appetite occurred in 28 (7.0%) and 78 (19.6%) patients,
respectively. Twenty-eight patients had decreased bicarbonate levels, but there
were no reports of respiratory alkalosis or metabolic acidosis. No changes in
vital signs of clinical concern were observed and there were no reports of
clinically significant electrocardiogram abnormalities with zonisamide treatment.
CONCLUSION: Zonisamide demonstrated an acceptable safety profile when used as
adjunctive treatment in paediatric patients.
PMID- 25128349
TI - Comparison of NaF and FDG PET/CT for assessment of treatment response in
castration-resistant prostate cancers with osseous metastases.
AB - BACKGROUND: Assessment of skeletal metastases' response to therapy is a highly
relevant but unresolved clinical problem. The main goal of this work was to
compare pharmacodynamic responses to therapy assessed with positron emission
tomography-computed tomography (PET/CT) using fluorine-18 sodium fluoride (NaF)
and fluorine-18 fluorodeoxyglucose (FDG) as the tracers. MATERIALS AND METHODS:
Patients with prostate cancer with known osseous metastases were treated with
zibotentan (ZD4054) and imaged with combined dynamic NaF/FDG PET/CT before
therapy (baseline), after 4 weeks of therapy (week 4), and after 2 weeks of
treatment break (week 6). Kinetic analysis allowed comparison of the voxel-based
tracer uptake rate parameter Ki, the vasculature parameters K1 (measuring
perfusion/permeability) and Vb (measuring vasculature fraction in the tissue),
and the standardized uptake values (SUVs). RESULTS: Correlations were high for
the NaF and FDG peak uptake parameters (Ki and SUV correlations ranged from 0.57
to 0.88) and for vasculature parameters (K1 and Vb correlations ranged from 0.61
to 0.81). Correlation was low between the NaF and FDG week 4 Ki responses (rho =
0.35; P = .084) but was higher for NaF and FDG week 6 Ki responses (rho = 0.72; P
< .0001). Correlations for vasculature responses were always low (rho < 0.35).
NaF and FDG uptakes in the osseous metastases were spatially dislocated, with
overlap in the range from 0% to 80%. CONCLUSION: This study found that late NaF
and FDG uptake responses are consistently correlated but that earlier uptake
responses and all vasculature responses can be unrelated. This study also
confirmed that FDG and NaF uptakes are spatially dislocated. Although treatment
responses assessed with NaF and FDG may be correlated, using both tracers
provides additional information.
PMID- 25128351
TI - Association of ICAM-1 K469E polymorphism with neurocysticercosis.
AB - Neurocysticercosis (NCC), a central nervous system (CNS) disease is caused by the
larval stage of Taenia solium. The disease is heterogeneous in clinical
presentation; some infected individuals develop symptoms and others may remain
symptom free. Impaired blood brain barrier allows recruitment of immune cells in
the CNS during infection and soluble intercellular adhesion molecule-1 (sICAM-1)
plays an important role in the recruitment of immune cells. We studied ICAM-1
K469E polymorphism among symptomatic and asymptomatic NCC patients. The study
revealed that individuals with variant (EE) genotype were more susceptible to
symptomatic NCC and also had an elevated level of sICAM-1.
PMID- 25128352
TI - [Vision and evolution of patient safety in Catalonia].
PMID- 25128353
TI - [Epidemiology of the hospital adverse events in Catalonia, Spain: a first step
for the patient safety improvement].
AB - It has been published that hospital adverse events are an important source of
morbidity and mortality in different countries and settings. The aim of this
study was to evaluate the frequency, magnitude, distribution and degree of
preventability of adverse events in the Autonomous Community of Catalonia
(Spain). We conducted a retrospective cohort study of 4,790 hospital discharges
that were selected by simple random sampling after stratified multistage sampling
in 15 hospitals in Catalonia. 38.25% of patients had positive risk criteria
(screening phase). We identified 356 cases of adverse events, which represent a
7.4% (95%CI: 6.7% to 8.1%). Of these, 43.5% (155 cases) were considered
preventable. This study confirms that adverse events in hospitals in Catalonia
are frequent, and generate a significant impact on morbidity and mortality. As in
other studies, corroborated that a high proportion of these adverse events are
considered preventable. It was possible to identify priority areas to focus
improvement efforts.
PMID- 25128354
TI - [Results of the implementation of the Bacteremia Zero project in Catalonia,
Spain].
AB - The nationwide Bacteremia Zero (BZ) Project consists in the simultaneous
implementation of measures to prevent central venous catheter-related bacteremia
(CVC-B) in critically ill patients and in the development of an integral safety
plan. The objective is to present the results obtained after the implementation
of the BZ project in the ICUs of the Autonomous Community of Catalonia, Spain.
All patients admitted to ICUs in Catalonia participating in the ENVIN-HELICS
registry between January 2009 and June 2010 were included. Information was
provided by 36 (92.3%) of the total possible 39 ICUs. A total of 281 episodes of
CVC-B were diagnosed (overall rate of 2.53 episodes per 1000 days of CVC). The
rates have varied significantly between ICUs that participated in the project for
more or less than 12 months (2.17 vs. 4.27 episodes per 1000 days of CVC,
respectively; p<.0001). The implementation of the BZ Project in Catalonia has
been associated with a decrease greater than 40% in the CVC-B rates in the ICUs
of this community, which is much higher than the initial objective of 4 episodes
per 1000 days of CVC).
PMID- 25128355
TI - [A surgical safety checklist implementation: experience of a start-up phase of a
collaborative project in hospitals of Catalonia, Spain].
AB - Surgical patient safety is a priority in the national and international quality
healthcare improvement strategies. The objective of the study was to implement a
collaborative intervention with multiple components and to evaluate the impact of
the patient surgical safety checklist (SSC) application. This is a prospective,
longitudinal multicenter study with a 7-month follow-up period in 2009 based on a
collaborative intervention for the implementation of a 24 item-SSC distributed in
3 different stages (sign in, time out, sign out) for its application to the
surgical patient. A total number of 27 hospitals participated in the strategy.
The global implementation rate was 48% (95%CI, 47.6%-48.4%) during the evaluation
period. The overall compliance with all the items of the SSC included in each
stage (sign in, time out, sign out) was 75,1% (95%CI, 73.5%-76.7%) for the sign
in, 77.1% (95%CI, 75.5%-78.6%) for the time out and 88.3% (95%CI, 87.2%-89.5%)
for the sign out respectively. The individual compliance with each item of the
SSC has remained above 85%, except for the surgical site marking with an
adherence of 67.4% (95%CI, 65.7%-69.1%)] and 71.2% (95%CI, 69.6%-72.9%)] in the
sign in and time out respectively. The SSC was successfully implemented to 48% of
the surgeries performed to the participating hospitals. The global compliance
with the SSC was elevated and the intervention trend was stable during the
evaluation period. Strategies were identified to allow of a higher number of
surgeries with application of the SSC and more professional involvement in
measures compliance such as surgical site marking.
PMID- 25128356
TI - [Study on the improvement of trauma patient care: TRAUMACAT project].
AB - Multiple injuries are a major source of morbidity and mortality in young people.
The aim of this study was to evaluate the effect of a collaborative strategy to
improve the implementation of six clinical indicators, recognized
internationally, for the treatment of trauma patient. Prospective, multicentre,
pre-and post-intervention study, in ten referral hospitals, offering polytrauma
care in Catalonia. 378 patients were recruited for the pre-intervention study and
501 for the post-intervention study. All patients had a history of high-energy
trauma requiring admission to critical or semi-critical care unit. INTERVENTION:
collaborative strategy aimed at participating professionals, involving the
creation of a panel of experts, appointment of monitors to encourage improvements
at each centre, training, distribution of information, material and meetings, to
exchange impressions. MAIN OUTCOME MEASURES: frequency and characteristics of
trauma and percentage of compliance with clinical indicators. Study of 879 trauma
patients. The injury mechanism was overall blunt trauma, in both pre and post
intervention phases. The medium ISS (injury severity score) was 21 +/- 12,8 and
the medium TRISS (trauma and injury severity score) was 26,4 +/- 11,4. We didn't
find differences between both study phases, in relation to the severity of
injury. The mortality rate was 11.5%. We observed significant improvement in the
performance of chest X-rays (45% vs. 62%) and pelvis X-rays (27% vs. 62%) in the
trauma box and in the fixation of the pelvis in patients with a fracture at this
site (24% vs. 49%). The use of diagnostic radiology in hemodynamically unstable
patients remained low (33%). The collaborative strategy was effective in
improving certain indicators of clinical management.
PMID- 25128357
TI - [Patient safety in primary care: PREFASEG project].
AB - The Institut Catala de la Salut (ICS) has designed and integrated in electronic
clinical station of primary care a new software tool to support the prescription
of drugs, which can detect on-line certain medication errors. The software called
PREFASEG (stands for Secure drug prescriptions) aims to prevent adverse events
related to medication use in the field of primary health care (PHC). This study
was made on the computerized medical record called CPT, which is used by all PHC
physicians in our institution -3,750- and prescribing physicians through it.
PREFASEG integrated in eCAP in July 2010 and six months later we performed a
cross-sectional study to evaluate their usefulness and refine their design. The
software alerts on-line in 5 dimensions: drug interactions, redundant treatments,
allergies, contraindications of drugs with disease, and advises against drugs in
over 75 years. PREFASEG generated 1,162,765 alerts (1 per 10 high treatment),
with the detection of therapeutic duplication (62%) the most alerted. The overall
acceptance rate is 35%, redundancies pharmacological (43%) and allergies (26%)
are the most accepted. A total of 10,808 professionals (doctors and nurses) have
accepted some of the recommendations of the program. PREFASEG is a feasible and
highly efficient strategy to achieve an objective of Quality Plan for the NHS.
PMID- 25128358
TI - [Intervention to improve hand hygiene compliance in Catalonia, Spain].
AB - Hand hygiene (HM) is the single most important measure and effective in reducing
the risk of Healthcare acquired infections (IRAS). Although HM is an effective,
simple and cheap measure, it is usual to find results of low compliance among
health professionals. The main objective of this strategy has been to give new
force to the promotion of HM in hospitals and educate professionals about the
importance of this single action. The strategy was planned as a multicenter
intervention study to promote HM in health centers of Catalonia in 2009-2010. The
intervention is based on 4 main areas: a survey of barriers and facilitators,
distribution of graphic material, training at different levels and measure of
quality indicators. With this strategy a total of 57% of the number of acute beds
in the concerted public and private network of hospitals were reached. The survey
revealed that training was perceived as the main facilitator of the HM action.
15,376 professionals registered to the on-line training. The overall compliance
with HM indications (based on "five moments for HM") was 56.45% in the acute
areas. The campaigns and programs to promote HM carried out in the last four
years in Catalonia has helped to achieve an increasing number of hospitals
associated to the strategy of the Alliance for Patient Safety in Catalonia. The
on-line curse acceptance was very high and seems a powerful tool to improve hand
hygiene knowledge and compliance among health professionals. The compliance of HM
seems to increase in the hospitals of Catalonia evaluated.
PMID- 25128359
TI - [Validation of the structure and resources of nosocomial infection control team
in hospitals ascribed to VINCat program in Catalonia, Spain].
AB - The main objective of this study was to validate the structure of the infection
control team (ICT) in the hospitals adhered to VINCat program and secondary
objective was to establish the consistency of resources of each center with the
requirements established by the program. Qualitative research consisting of an
ethnographic study using participant observation during the years 2008-2010. The
centers were stratified in three groups by complexity and beds. The instrument
was a semistructured interview to members of the ICT. The transcription of the
interview was sent to informants for validation. In November 2010 a questionnaire
regarding human resources and number hours dedicated to the ICT was sent. During
2008-2010, 65 centers had been adhered to VINCat program. In 2010, the ICT of
Group I hospitals had a mean of two physician, one in full-time and one nurse for
every 230 beds. In Group II, one physician part-time and one nurse per 180 beds
and in Group III a physician and a nurse for every 98 beds, both part-time. In
2010, all hospitals had a structured ICT, an operative infection committee, and a
hospital member representing the center at the program as well as enough
electronic resources. The hospitals participating in the program have now VINCat
an adequate surveillance structure and meet the minimum technical and human
resources required to provide high-quality data. However human resources are not
guaranteed.
PMID- 25128360
TI - [Design, implementation and evaluation of a management model of patient safety in
hospitals in Catalonia, Spain].
AB - Since its inception in 2006, the Alliance for Patient Safety in Catalonia has
played a major role in promoting and shaping a series of projects related to the
strategy of the Ministry of Health, Social Services and Equality, for improving
patient safety. One such project was the creation of functional units or
committees of safety in hospitals in order to facilitate the management of
patient safety. The strategy has been implemented in hospitals in Catalonia which
were selected based on criteria of representativeness. The intervention was based
on two lines of action, one to develop the model framework and the other for its
development. Firstly the strategy for safety management based on EFQM (European
Foundation for Quality Management) was defined with the development of standards,
targets and indicators to implement security while the second part involved the
introduction of tools, methodologies and knowledge to the management support of
patient safety and risk prevention. The project was developed in four hospital
areas considered higher risk, each assuming six goals for safety management. Some
of these targets such as the security control panel or system of adverse event
reporting were shared. 23 hospitals joined the project in Catalonia. Despite the
different situations in each centre, high compliance was achieved in the
development of the objectives. In each of the participating areas the security
control panel was developed. Stable structures for safety management were
established or strengthened. Training in patient safety played and important
role, 1415 professionals participated. Through these kind of projects not only
have been introduced programs of proven effectiveness in reducing risks, but they
also provide to the facilities a work system that allows autonomy in diagnosis
and analysis of the different risk situations or centre specific safety issues.
PMID- 25128361
TI - [Notification of incidents related to patient safety in hospitals in Catalonia,
Spain during the period 2010-2013].
AB - The aim of this paper is to discover the aggregated results of a general
notification system for incidents related to patient safety implemented in
Catalan hospitals from 2010 to 2013. Observational study describing the incidents
notified from January 2010 to December 2013 from all hospitals in Catalonia
forming part of the project to create operational patient safety management
units. The Patient Safety Notification and Learning System (SiNASP) was used.
This makes it possible to classify incidents depending on the area where they
occur, the type of incident notified, the consequences, the seriousness according
to the Severity Assessment Code (SAC) and the profession of the notifying party,
as the principal variables. The system was accessed via the Internet (SiNASP
portal). Access was voluntary and anonymous or with a name given and later
removed. During the study period, notification of a total of 5,948 incidents came
from 22-29 hospitals. 5,244 of the incidents were handled by the centres and
these are the ones analysed in the study. 64% (3,380) affected patients, 18%
(950) created a situation capable of causing an incident and 18% (914) did not
affect patients. 26% of incidents that affected patients (864) caused some kind
of harm. Most incidents occurred during hospitalisation (54%) and in casualty
(15%), followed by the ICU (9%) and the surgical block (8%). The most frequent
notifying parties were nurses (71%) followed by doctors (15%) and pharmacists
(9%). In terms of severity, most incidents were classified as low-risk (37%) or
incidents that did not affect the patient (36%). However, 40 cases (0.76%) of
extreme risk should be highlighted. In terms of the types of incident notified,
most were due to a medication error (26.8%), followed by falls (16.3%) and
patient identification (10.6%). The majority of notifications were incidents that
affected patients and, of these, 26% caused harm. In general, they occurred in
hospitalisation units and notification was mostly given by nurses. The incident
notification system is a tool that complements others for promoting a patient
safety culture and defining the risk profile of a health organisation. The
opportunity for learning from experience is the reason for the existence of the
notification system.
PMID- 25128362
TI - [Optimization of radiological scoliosis assessment].
AB - Most scoliosis are idiopathic (80%) and occur more frequently in adolescent
girls. Plain radiography is the imaging method of choice, both for the initial
study and follow-up studies but has the disadvantage of using ionizing radiation.
The breasts are exposed to x-ray along these repeated examinations. The authors
present a range of recommendations in order to optimize radiographic exam
technique for both conventional and digital x-ray settings to prevent unnecessary
patients' radiation exposure and to reduce the risk of breast cancer in patients
with scoliosis. With analogue systems, leaded breast protectors should always be
used, and with any radiographic equipment, analog or digital radiography, the
examination should be performed in postero-anterior projection and optimized low
dose techniques. The ALARA (as low as reasonable achievable) rule should always
be followed to achieve diagnostic quality images with the lowest feasible dose.
PMID- 25128363
TI - [Accreditation model for acute hospital care in Catalonia, Spain].
AB - The implementation of an accreditation model for healthcare centres in Catalonia
which was launched for acute care hospitals, leaving open the possibility of
implementing it in the rest of lines of service (mental health and addiction,
social health, and primary healthcare centres) is described. The model is based
on the experience acquired over more tan 31 years of hospital accreditation and
quality assessment linked to management. In January 2006 a model with
accreditation methodology adapted to the European Foundation for Quality
Management (EFQM) model was launched. 83 hospitals are accredited, with an
average of 82.6% compliance with the standards required for accreditation. The
number of active assessment bodies is 5, and the accreditation period is 3 years.
A higher degree of compliance of the so-called "agent" criteria with respect to
"outcome" criteria is obtained. Qualitative aspects for implementation to be
stressed are: a strong commitment both from managers and staff in the centres, as
well as a direct and fluent communication between the accreditation body
(Ministry of Health of the Government of Catalonia) and accredited centres.
Professionalism of audit bodies and an optimal communication between audit bodies
and accredited centres is also added.
PMID- 25128364
TI - [Catalonia's primary healthcare accreditation model: a valid model].
AB - There are few experiences of accreditation models validated by primary care teams
(EAP). The aim of this study was to detail the process of design, development,
and subsequent validation of the consensus EAP accreditation model of Catalonia.
An Operating Committee of the Health Department of Catalonia revised models
proposed by the European Foundation for Quality Management, the Joint Commission
International and the Institut Catala de la Salut and proposed 628 essential
standards to the technical group (25 experts in primary care and quality of
care), to establish consensus standards. The consensus document was piloted in 30
EAP for the purpose of validating the contents, testing standards and identifying
evidence. Finally, we did a survey to assess acceptance and validation of the
document. The Technical Group agreed on a total of 414 essential standards. The
pilot selected a total of 379. Mean compliance with the standards of the final
document in the 30 EAP was 70.4%. The standards results were the worst fulfilment
percentage. The survey target that 83% of the EAP found it useful and 78% found
the content of the accreditation manual suitable as a tool to assess the quality
of the EAP, and identify opportunities for improvement. On the downside they
highlighted its complexity and laboriousness. We have a model that fits the
reality of the EAP, and covers all relevant issues for the functioning of an
excellent EAP. The model developed in Catalonia is a model for easy
understanding.
PMID- 25128365
TI - Should we advise patients with lupus to quit smoking?
PMID- 25128366
TI - Quantification of V(D)J recombination by real-time quantitative PCR.
AB - B and T lymphocytes have the unique capacity to somatically rearrange their
antigen receptor loci through V(D)J recombination. D-JH and VH-DJH recombination
events are usually visualized by semi-quantitative PCR followed by detection of
end products, which is time consuming and requires the use of hazardous elements.
Additionally, it necessitates relatively large amounts of genomic DNA which could
be limiting when the cell populations of interest are rare. Here, we describe a
real-time quantitative PCR assay for a fast quantification of V(D)J recombination
events at the IgH locus.
PMID- 25128367
TI - Electrochemical performance and detection of 8-Hydroxy-2'-deoxyguanosine at
single-stranded DNA functionalized graphene modified glassy carbon electrode.
AB - 8-Hydroxy-2'-deoxyguanosine (8-OH-dG) is the most abundant oxidative product of
DNA and it is also considered to be a biomarker of oxidative DNA damage. In this
work, a novel biosensor was fabricated by combining the biocompatibility of
single-stranded DNA (ss-DNA) and the excellent conductivity of graphene
nanosheets (GNs). The biosensor showed high electrocatalytic activity to the
oxidation of 8-OH-dG. The sensitivities were 13.23 (+/-0.03)MUA MUM(-1), 5.827
(+/-0.008) MUA MUM(-1) and 3.086 (+/-0.005) MUA MUM(-1) in the concentration
ranges of 0.0056-1.155 MUM, 1.155-11.655 MUM and 11.655-36.155 MUM, respectively.
The detection limit was 0.875 nM (S/N=3). Furthermore, the electrochemical
behavior of 8-OH-dG was also investigated in detail in the presence of uric acid.
And the results showed that uric acid had interference with the trace detection
of 8-OH-dG. But it can be eliminated completely by uricase. The as-prepared ss
DNA/GNs/GCE will be promising for the detection of 8-OH-dG in real samples.
PMID- 25128368
TI - Associations between different types of hypoglycemic agents and the clinical
outcome of percutaneous coronary intervention in diabetic patients-From the FU
Registry.
AB - BACKGROUND: It is not clear whether it is reasonable to use particular drugs for
glycemic control in preference to other hypoglycemic agents in terms of the
clinical outcome of percutaneous coronary intervention (PCI) in patients with
diabetes mellitus (DM). METHODS AND RESULTS: Among 2148 patients (2568 lesions)
in the FU-Registry, DM patients who underwent PCI (n=758; 922 lesions) were
investigated to clarify the effects of various drugs for glycemic control on the
clinical outcome [major adverse cardiac events (MACEs): death, myocardial
infarction (MI), and target lesion revascularization (TLR)] over approximately
300 days of follow-up (UMIN000005679). The MACEs(+) group (n=165) had a higher
usage of insulin (p<0.001) and a lower usage of biguanides (BG, p<0.05) and
dipeptidyl peptidase-IV inhibitors (p<0.05) at PCI, compared to the MACEs(-)
group (n=593). A multivariate logistic regression analysis showed that low
density lipoprotein cholesterol, insulin use, atherosclerosis obliterans, and
lesion reference might be significantly associated with MACEs, while BG use was
negatively correlated with MACEs (p=0.04). The cumulative frequency of MACEs in
the insulin-treated group was significantly higher (p<0.05) than that in the non
insulin group, and the strongest association between insulin with MACEs was seen
in the hemoglobin (Hb) A1c 6.5-7.5% group. There tended to be a negative
correlation between the use of insulin and MACEs, with risk ratios of <1, for the
HbA1c >8.5% groups. CONCLUSIONS: Among different hypoglycemic agents, treatment
with insulin was associated with poor mid-term clinical outcomes in DM patients
who underwent PCI, while BG use was negatively correlated with MACEs. It may be
reasonable for patients with HbA1c >8.5% to avoid hyperglycemia and
glucotoxicity, even through the use of insulin.
PMID- 25128369
TI - Expression of Caenorhabditis elegans-expressed Trans-HPS, partial aminopeptidase
H11 from Haemonchus contortus.
AB - Aminopeptidase H11 present in the surface of intestine microvilli in Haemonchus
contortus was identified as the most effective antigen candidate. However, its
recombinant forms produced in Escherichiacoli, insect cells and yeast could not
provide promising protection against H. contortus challenge, probably due to the
inappropriate glycosylation and/or conformational folding. Herein, partial H11
containing the potential zinc-binding domain and two predicted glycosylation
sites (nt 1 bp-1710 bp, Trans-HPS) was subcloned downstream of 5' flanking region
of Caenorhabditis elegans cpr-1 gene in pPD95.77 vector, with the deletion of GFP
gene. The recombinant was expressed in C. elegans and verified by blotting with
anti-H11 and anti-Trans-HPS rabbit polyclonal antibodies and anti-His monoclonal
antibody. Stably inherited Trans-HPS in worm descendants was achieved by
integration using UV irradiation. Immunization with the crude Trans-HPS extracted
from transgenic worms resulted in 37.71% reduction in faecal egg counts (FEC)
(P<0.05) and 24.91% reduction in worm burden, but an upward curve with moderate
rate of daily FEC in goats. These results suggested an apparent delay against H.
contortus egg-laying in goats, which differed from that with bacteria-origin form
of partial H11 (nt 670 bp-1710 bp, HPS) (26.04% reduction in FEC and 18.46%
reduction in worm burden). These findings indicate the feasibility of sufficient
C. elegans-expressed H11 for the immunological research and vaccine development.
PMID- 25128370
TI - Facts, myths and hypotheses on the zoonotic nature of Mycobacterium avium
subspecies paratuberculosis.
AB - Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of
paratuberculosis (Johne's disease [JD]), a chronic granulomatous enteritis in
ruminants. JD is one of the most widespread bacterial diseases of domestic
animals with significant economic impact. The histopathological picture of JD
resembles that of Crohn's disease (CD), a human chronic inflammatory bowel
disease of still unresolved aetiology. An aetiological relevance of MAP for CD
has been proposed. This and the ambiguity of other published epidemiological
findings raise the question whether MAP represents a zoonotic agent. In this
review, we will discuss evidence that MAP has zoonotic capacity.
PMID- 25128371
TI - Implementation and monitoring of oral rabies vaccination of foxes in Kosovo
between 2010 and 2013--an international and intersectorial effort.
AB - The European Union has used instrument for pre-accession (IPA) funds to provide
technical assistance and supplies for the eradication, monitoring and control of
rabies in several pre-accession countries. As a result, since 2010, multi-annual
oral rabies vaccination (ORV) programmes for eliminating fox rabies have been
launched in six Western Balkan countries. Here the implementation of the ORV
programme in Kosovo, the smallest of the West Balkan countries, is described.
Associated challenges under difficult political conditions, potential biases, and
the results of rabies surveillance and monitoring of ORV campaigns (bait uptake
and immunisation rates) since 2010 are reported.
PMID- 25128372
TI - Joint issues--conflicts of interest, the ASR hip and suggestions for managing
surgical conflicts of interest.
AB - BACKGROUND: Financial and nonfinancial conflicts of interest in medicine and
surgery are troubling because they have the capacity to skew decision making in
ways that might be detrimental to patient care and well-being. The recent case of
the Articular Surface Replacement (ASR) hip provides a vivid illustration of the
harmful effects of conflicts of interest in surgery. DISCUSSION: We identify
financial and nonfinancial conflicts of interest experienced by surgeons,
hospitals and regulators in the ASR case. These conflicts may have impacted
surgical advice, decision-making and evidence gathering with respect to the ASR
prosthesis, and contributed to the significant harms experienced by patients in
whom the hip was implanted. Drawing on this case we explore shortcomings in the
standard responses to conflicts of interest--disclosure and recusal. We argue
disclosure is necessary but by no means sufficient to address conflicts of
interest. Using the concept of recusal we develop remedies including second
opinions and third party consent which may be effective in mitigating conflicts,
but their implementation introduces new challenges. SUMMARY: Deployment of the
ASR hip is a case of surgical innovation gone wrong. As we show, there were
multiple conflicts of interest involved in the introduction of the ASR hip into
practice and subsequent attempts to gloss over the mounting body of evidence
about its lack of safety and effectiveness. Conflicts of interest in surgery are
often not well managed. We suggest strategies in this paper which can minimise
the conflicts of interest associated with surgical innovation.
PMID- 25128373
TI - Application and assessment of optical clearing methods for imaging of tissue
engineered neural stem cell spheres.
AB - Three-dimensional (3D) cell culture is an important tool that facilitates
biological discoveries by bridging the divide between standard two-dimensional
cell culture and the complex, high-cell-density in vivo environment. Typically,
the internal structures of 3D tissue-engineered samples are visualized through an
involved process of physical sectioning, immunostaining, imaging, and
computational reconstruction. However, recent progress in tissue-clearing methods
has improved optical-imaging-depth capabilities in whole embryos and brains by
reducing tissue opacity and light scattering, thus decreasing the need for
physical sectioning. In this study, we assessed the application of the recently
published clearing techniques Clear(T2), Scale, and SeeDB to tissue-engineered
neural spheres. We found that scaffold-free self-assembled adult hippocampal
neural stem cell spheres of 100-MUm diameter could be optically cleared and
imaged using either Clear(T2) or Scale, while SeeDB only marginally improved
imaging depth. The Clear(T2) protocol maintained sphere size, while Scale led to
sample expansion, and SeeDB led to sample shrinkage. Additionally, using
Clear(T2) we cleared and successfully imaged spheres of C6 glioma cells and
spheres of primary cortical neurons. We conclude that Clear(T2) is the most
effective protocol of those tested at clearing neural spheres of various cell
types and could be applied to better understand neural cell interactions in 3D
tissue-engineered samples.
PMID- 25128374
TI - siRNA therapy in cutaneous T-cell lymphoma cells using polymeric carriers.
AB - Cutaneous T-cell lymphomas (CTCLs) arise from specific molecular aberrations that
lead to uncontrolled cell proliferation. RNA interference (RNAi) with short
interfering RNAs (siRNAs) is a feasible approach to interrupt aberrant signal
processing in CTCL cells, but functional biomaterial carriers are needed to
effectively deliver siRNAs intracellularly. Towards this goal, we explored the
utility of lipid-substituted polyethylenimines (PEI) carriers in a cell model of
CTCL. Using caprylic and linoleic acid substituted 2 kDa PEI (PEI-CA and PEI-LA,
respectively), we showed effective delivery of siRNA to T-lymphocyte Hut78 and
Jurkat cells, but silencing of a model protein (Green Fluorescent Protein, GFP)
was possible only in the Hut78 cells. To enhance siRNA delivery to Hut78 cells, a
high siRNA: carrier ratio used to assemble the complexes and centrifugation of
cells in the presence of complexes were found effective. The toxicities of PEI-CA
and PEI-LA were significantly lower than other commercial carriers, 25 kDa PEI
and Lipofectamine((r)) RNAiMAX. This might have contributed to reduced siRNA
delivery efficiency of the latter carriers. Screening several endogenous targets
led us to identify phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and
cyclin-dependent kinase 18 (CDK18) as viable targets to induce siRNA-mediated
cell growth inhibition. The results of this study identified promising polymeric
carriers and molecular targets that could control proliferation of CTCL cells
based on RNAi therapy.
PMID- 25128375
TI - Chronic tissue response to carboxymethyl cellulose based dissolvable insertion
needle for ultra-small neural probes.
AB - Implantable neural electrodes must drastically improve chronic recording
stability before they can be translated into long-term human clinical
prosthetics. Previous studies suggest that sub-cellular sized and mechanically
compliant probes may result in improved tissue integration and recording
longevity. However, currently these design features are restricted by the
opposing mechanical requirements needed for minimally damaging insertions. We
designed a non-cytotoxic, carboxymethylcellulose (CMC) based dissolvable delivery
vehicle (shuttle) to provide the mechanical support for insertion of ultra-small,
ultra-compliant microfabricated neural probes. Stiff CMC-based shuttles rapidly
soften immediately after being placed ~1 mm above an open craniotomy as they
absorb vapors from the brain. To address this, we developed a sophisticated
targeting, high speed insertion (~80 mm/s), and release system to implant these
shuttles. After implantation, the goal is for the shuttle to dissolve away
leaving only the electrodes behind. Here we show the histology of chronically
implanted shuttles of large (300 MUm * 125 MUm) and small (100 MUm * 125 MUm)
size at discrete time points over 12 weeks. Early time points show the CMC
shuttle expanded after insertion as it absorbed moisture from the brain and
slowly dissolved. At later time points neuronal cell bodies populate regions
within the original shuttle tract. The large CMC shuttles show that the CMC
expansion can cause extended secondary damage. On the other hand, the smaller CMC
shuttles show limited secondary damage, wound closure by 4 weeks, absence of
activated microglia at 12 weeks, as well as evidence suggesting neural
regeneration at the implant site. This shuttle, therefore, shows great promise
facilitating the implantation of nontraditional ultra-small, and ultra-compliant
probes.
PMID- 25128376
TI - The influence of age on adaptive bone formation and bone resorption.
AB - Bone is a tissue with enormous adaptive capacity, balancing resorption and
formation processes. It is known that mechanical loading shifts this balance
towards an increased formation, leading to enhanced bone mass and mechanical
performance. What is not known is how this adaptive response to mechanical
loading changes with age. Using dynamic micro-tomography, we show that structural
adaptive changes of trabecular bone within the tibia of living mice subjected to
two weeks of in vivo cyclic loading are altered by aging. Comparisons of 10, 26
and 78 weeks old animals reveal that the adaptive capacity diminishes.
Strikingly, adaptation was asymmetric in that loading increases formation more
than it reduces resorption. This asymmetry further shifts the (re)modeling
balance towards a net bone loss with age. Loading results in a major increase in
the surface area of mineralizing bone. Interestingly, the resorption thickness is
independent of loading in trabecular bone in all age groups. This data suggests
that during youth, mechanical stimulation induces the recruitment of bone
modeling cells whereas in old age, only bone forming cells are affected. These
findings provide mechanistic insights into the processes that guide skeletal
aging in mice as well as in other mammals.
PMID- 25128379
TI - Lippes Loop intrauterine device left in the uterus for 50 years: case report.
AB - BACKGROUND: The first Lippes Loop intrauterine device (IUD) was introduced in
1962. It was a plastic double "S" loop, a trapezoid shaped IUD that closely fit
around the contours of the uterine cavity, reducing the incidence of expulsion.
This IUD was commonly used from the 1960's to the 1980's. Some authors state that
the IUD can be left in the uterine cavity for an indefinite amount of time.
Prolonged use of this device was common, however, it was associated with some
complications like uterine bleeding during post-menopausal period and
inflammatory pelvic diseases. CASE PRESENTATION: The patient was a 74-years-old
woman who was admitted to a university hospital due to urinary incontinence
stress. The patient's history included 2 deliveries and 20 years of menopause.
During ultrasonography a normally sized and shaped uterus was found. The uterine
cavity was expanded by 14 mm with some fluid. A "Lippes" loop was also seen in
the uterine cavity. Both ovaries were atrophic without any abnormalities. The
patient had her IUD inserted 50 years ago. Patient underwent TOT (tension
obturator tape ) surgery for urinary incontinence. Evacuation of IUD and uterine
curettage was also done. CONCLUSIONS: Fifty years of prolonged usage of LIPPES
IUD had no influence on the woman's health during our case.
PMID- 25128377
TI - Ischemic preconditioning affects long-term cell fate through DNA damage-related
molecular signaling and altered proliferation.
AB - Despite the potential of ischemic preconditioning for organ protection, long-term
effects in terms of molecular processes and cell fates are ill defined. We
determined consequences of hepatic ischemic preconditioning in rats, including
cell transplantation assays. Ischemic preconditioning induced persistent
alterations; for example, after 5 days liver histology was normal, but gamma
glutamyl transpeptidase expression was observed, with altered antioxidant enzyme
content, lipid peroxidation, and oxidative DNA adducts. Nonetheless, ischemic
preconditioning partially protected from toxic liver injury. Similarly, primary
hepatocytes from donor livers preconditioned with ischemia exhibited undesirably
altered antioxidant enzyme content and lipid peroxidation, but better withstood
insults. However, donor hepatocytes from livers preconditioned with ischemia did
not engraft better than hepatocytes from control livers. Moreover, proliferation
of hepatocytes from donor livers preconditioned with ischemia decreased under
liver repopulation conditions. Hepatocytes from donor livers preconditioned with
ischemia showed oxidative DNA damage with expression of genes involved in MAPK
signaling that impose G1/S and G2/M checkpoint restrictions, including p38 MAPK
regulated or ERK-1/2-regulated cell-cycle genes such as FOS, MAPK8, MYC, various
cyclins, CDKN2A, CDKN2B, TP53, and RB1. Thus, although ischemic preconditioning
allowed hepatocytes to better withstand secondary insults, accompanying DNA
damage and molecular events simultaneously impaired their proliferation capacity
over the long term. Mitigation of ischemic preconditioning-induced DNA damage and
deleterious molecular perturbations holds promise for advancing clinical
applications.
PMID- 25128378
TI - Psycho-social impact of visual impairment on health-related quality of life among
nursing home residents.
AB - BACKGROUND: Visual impairment (VI) affects physical, psychological, and emotional
well-being, and social life as well. The purpose of this exploratory study was to
assess the psycho-social impact of VI on health-related quality of life (HRQoL)
among nursing home residents. METHODS: This cross-sectional study involved 272
residents of 60 years or older residing in seven nursing homes of the Kathmandu
Valley, Nepal. Comprehensive ocular examinations, including near and distance
vision assessment and refractions were carried out. VI was defined as visual
acuity (VA) less than 6/18 in the better eye. Residents were divided into two
groups: one group did not have VI (in whom VA was greater than or equal to 6/18
in the better eye), and the other had VI (in whom VA was worse than 6/18 in the
better eye).Face-to-face interviews were conducted filling out a 36-item The
Medical Outcomes Study Short-Form (SF-36) questionnaire. The SF-36 questionnaire
was scored according to the scoring algorithm SF-36 subscales. RESULTS: The mean
age of residents was 74.68 +/- 8.19 years (range, 60-99 years) and the majority
were female (78.68%). The mean composite score of SF-36 was 46.98 +/- 13.08. VI
detrimentally affected scores of both the physical and the mental components, but
the impact of VI was slightly greater for the physical component than that for
the mental component. There was a trend towards a lower composite score as well
as each subscale score of the SF-36 in participants with VI than in those without
VI. CONCLUSION: VI has a negative effect on HRQoL. HRQoL is reduced among nursing
home residents and the reduction in the HRQoL bears a positive association with
VI.
PMID- 25128380
TI - [Some points on the diagnosis of microscopic colitis].
PMID- 25128381
TI - Doxycycline exerts multiple anti-allergy effects to attenuate murine allergic
conjunctivitis and systemic anaphylaxis.
AB - Allergic diseases, which affect up to 20-30% of the world population, are still
therapeutic challenge for allergists. Tetracyclines, which belong to an
antibiotic drug family that possesses a striking variety of non-antibiotic
properties, have been successfully applied to a wide range of diseases. However,
their roles in allergic conjunctivitis and anaphylaxis and their underlying anti
allergy mechanisms remain elusive. Here, we reported that treatment with
doxycycline significantly reduced IgE release from mouse B cells and the
degranulation and inflammatory cytokines production of mouse mast cells (MCs)
activated by IgE-dependent way. Furthermore, doxycycline treatment significantly
inhibited histamine-induced vascular hyperpermeability in vitro. Mechanistically,
the doxycycline-mediated inhibition of B cells, MCs and histamine may occur via
modulation of the PI3K/Akt pathway. In vivo, our results demonstrated that
treatment with doxycycline significantly attenuated clinical symptoms of mouse
models of experimental allergic conjunctivitis (EAC) with a significant decrease
in inflammatory cell frequency, IgE production, histamine release, and a decrease
in TNF-alpha and IL-4 production. Using mouse models of MCs-dependent passive
systemic anaphylaxis (PSA), we further confirmed anti-allergy effects of
doxycycline and doxycycline-mediated inhibitory effects on MCs. Furthermore, our
results showed that doxycycline significantly attenuate histamine-induced
systemic anaphylaxis-like reaction (HISA) with a significantly downregulation of
PI3K/Akt/eNOS/VE-cadherin pathway. The doxycycline-mediated anti-allergy effects
during EAC, PSA and HISA were abrogated when an Akt activator, SC79, was
administered. These findings suggest that doxycycline inhibits B cell, MC and
histamine function and attenuates experimental allergic conjunctivitis and
systemic anaphylaxis by possible modulating the PI3K/Akt pathway.
PMID- 25128382
TI - Paris saponin VII suppressed the growth of human cervical cancer Hela cells.
AB - BACKGROUND: Saponins of several herbs are known to induce apoptosis in many
cancer cells. The present study aimed to investigate the growth inhibitory effect
of Paris saponin VII (PS VII), a kind of steroidal saponins from Chonglou
(Rhizoma Paridis Chonglou), on the human cervical cancer cell line Hela and the
relative molecular mechanisms. METHODS: Hela cells were exposed to different
concentrations of PS VII (1 to 100 MUM). Inhibition of cell proliferation was
measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
and 5-ethynyl-2'-deoxyuridine (EdU) assays. The amount of apoptotic cells was
evaluated by flow cytometric analysis. And the protein level of cleaved caspase
3, cleaved caspase-9, Bax, and Bcl-2 was evaluated by Western blot. RESULTS: The
half maximal inhibitory concentration (IC50) value of PS VII for the growth
inhibition of Hela cells was 2.62 +/- 0.11 MUM. PS VII increased the expression
of caspase-3, caspase-9, and Bax while decreased that of Bcl-2, suggesting that
PS VII may induce apoptosis through intrinsic apoptotic ways. CONCLUSIONS: These
data indicate that PS VII has the potential for the treatment of cervical cancer.
PMID- 25128383
TI - Radiodense ligament markers for radiographic evaluation of anterior cruciate
ligament reconstruction.
AB - INTRODUCTION: Early clinical and radiographic diagnosis of failed or loosened
anterior cruciate ligament (ACL) reconstructions can be challenging. The aim of
the present study is to retrospectively evaluate the use of radiologically
visible markers in the ACL graft, serving as a potential diagnostic tool in ACL
graft rupture and insufficiency. METHODS: Twenty patients were included in the
study. ACL reconstruction was performed with use of a hamstring autograft in
hybrid fixation technique. The graft was marked with two radiodense suture knots,
one at the tibial and femoral tunnel openings. Radiographs were performed
postoperatively, after 6 weeks and 12 months. Four distances between markers and
landmarks were measured in anteroposterior and three in lateral radiographic
views and the positional change between the timepoints of measurement was
calculated. RESULTS: Measurements of the marker distances on radiographs showed
an excellent interobserver reliability (kappa=0.97). In two measured distal
anteroposterior distances statistically significant changes could be detected
between 6 weeks and 12 months postoperatively in one patient with MRI-documented
ACL rerupture and in five patients with ACL elongation defined as anteroposterior
translation with side-to-side difference of >=3 mm measured with a Rolimeter
device. On lateral radiographs, marker distances were highly variable and did not
correlate with clinical ACL elongation. CONCLUSION: The application of radiodense
ACL graft markers is a straight-forward, non-expensive and potentially useful
diagnostic tool to identify the position of the transplant and for diagnosis of
graft elongation or failure. However, the method is sensitive to the radiological
projection, which should be further studied and optimized.
PMID- 25128384
TI - Coronal tibiofemoral subluxation: a new measurement method.
AB - BACKGROUND: Coronal tibiofemoral (CTF) subluxation is a common finding in knee
osteoarthritis (OA) which can be related to poor pain scores and tibial spine
impingement. In this study we describe a new method for measuring CTF subluxation
and present validation of the method using cadaveric knees. METHODS: A prototype
software code based on the ICP mathematical algorithm was developed to measure
CTF subluxation; the code finds the rigid transformation that best aligns the
articular surfaces, measures CTF subluxation and the angle between articular
surfaces. For validation, three stripped fresh frozen cadaveric knee specimens
were transfixed to a specially designed knee fixation device where tibiofemoral
angle and CTF subluxation can be measured directly. Fluoroscopic images were
obtained with the tibiofemoral joint in neutral alignment and with 5, 10 and 15
(mm) of medial and lateral subluxation. This procedure was repeated with a
neutral tibiofemoral angle, 10 degrees of varus and 10 degrees of valgus. All
images were analyzed independently by two investigators using the prototype
software. RESULTS: The interclass correlation coefficient between the two
investigators for CTF subluxation and tibiofemoral angle was 0.93 and 0.99
respectively. The CTF subluxation and tibiofemoral angle measured by the software
correlated to the CTF subluxation and tibiofemoral angle were defined using the
knee fixation device, with Pearson product moments of 0.86 and 0.94 respectively.
CONCLUSION: Our suggested prototype software is precise, repeatable and reliable
at measuring CTF subluxation and tibiofemoral angle. It may prove to be a useful
tool to evaluate CTF subluxation in a clinical setting.
PMID- 25128385
TI - National health policy-makers' views on the clarity and utility of Countdown to
2015 country profiles and reports: findings from two exploratory qualitative
studies.
AB - BACKGROUND: The use of sets of indicators to assess progress has become
commonplace in the global health arena. Exploratory research has suggested that
indicators used for global monitoring purposes can play a role in national policy
making, however, the mechanisms through which this occurs are poorly understood.
This article reports findings from two qualitative studies that aimed to explore
national policy-makers' interpretation and use of indicators from country
profiles and reports developed by Countdown to 2015. METHODS: An initial study
aimed at exploring comprehension of Countdown data was conducted at the 2010
joint Women Deliver/Countdown conference. A second study was conducted at the
64th World Health Assembly in 2011, specifically targeting national policy
makers. Semi-structured interviews were carried out with 29 and 22 participants,
respectively, at each event. Participants were asked about their understanding of
specific graphs and indicators used or proposed for use in Countdown country
profiles, and their perception of how such data can inform national policy
making. Responses were categorised using a framework analysis. RESULTS:
Respondents in both studies acknowledged the importance of the profiles for
tracking progress on key health indicators in and across countries, noting that
they could be used to highlight changes in coverage, possible directions for
future policy, for lobbying finance ministers to increase resources for health,
and to stimulate competition between neighbouring or socioeconomically similar
countries. However, some respondents raised questions about discrepancies between
global estimates and data produced by national governments, and some struggled to
understand the profile graphs shown in the absence of explanatory text. Some
respondents reported that use of Countdown data in national policy-making was
constrained by limited awareness of the initiative, insufficient detail in the
country profiles to inform policy, and the absence of indicators felt to be more
appropriate to their own country contexts. CONCLUSIONS: The two studies emphasise
the need for country consultations to ensure that national policy-makers
understand how to interpret and use tools like the Countdown profile for planning
purposes. They make clear the value of qualitative research for refining tools
used to promote accountability, and the need for country level Countdown-like
processes.
PMID- 25128386
TI - The histone deacetylase inhibitor trichostatin A induces neurite outgrowth in
PC12 cells via the epigenetically regulated expression of the nur77 gene.
AB - Histone deacetylase (HDAC) inhibitors induce histone acetylation and gene
expression by changing local chromatin structures. They can thereby influence
various cells to proliferate or differentiate. It has been reported that
trichostatin A (TSA) or valproic acid (VPA) can induce the neuronal
differentiation of mouse embryonic neural stem cells and rat cerebellar granule
cells. It is unclear however which gene is responsible for the neuronal
differentiation induced by HDAC inhibitors. In this study, we investigated the
contribution of immediate early gene (IEG) nur77 to the neuronal differentiation
induced by TSA. We report that TSA induces neurite outgrowth in PC12 cells, and
C646, an inhibitor of HAT (histone acetyl transferase) (p300), prevents TSA
induced neurite formation. The acetylation of the Lys14 residue of histone H3,
and mRNA and protein expression of nur77 gene were found to be stimulated after
treatment with TSA, but not in the presence of C646. A knock-down of nur77
inhibits the neurite outgrowth induced by TSA. Furthermore, the ectopic
expression of nur77 significantly elicits neurite formation in PC12 cells. These
results suggest that the expression of nur77, which is up-regulated via the TSA
induced acetylation of Lys14 on histone H3, is essential for the neuronal
differentiation in TSA-induced PC12 cells.
PMID- 25128389
TI - Mesenchymal change and drug resistance in neuroblastoma.
AB - BACKGROUND: Metastatic initiation has many phenotypic similarities to epithelial
to-mesenchymal transition, including loss of cell-cell adhesion, increased
invasiveness, and increased cell mobility. We have previously demonstrated that
drug resistance is associated with a metastatic phenotype in neuroblastoma (NB).
The purpose of this project was to determine if the development of doxorubicin
resistance is associated with characteristics of mesenchymal change in human NB
cells. MATERIALS AND METHODS: Total RNA was isolated from wild type (WT) and
doxorubicin-resistant (DoxR) human NB cell lines (SK-N-SH and SK-N-BE(2)C) and
analyzed using the Illumina Human HT-12 version 4 Expression BeadChip.
Differentially expressed genes (DEGs) were identified. Volcano plots and heat
maps were generated. Genes of interest with a fold change in expression >1.5 and
an adjusted P < 0.1 were analyzed. Immunofluorescence (IF) and Western blot
analysis confirmed microarray results of interest. Matrigel invasion assay and
migration wounding assays were performed. RESULTS: Volcano plots and heat maps
visually demonstrated a similar pattern of DEGs in the SK-N-SH and SK-N-BE(2)C
DoxR cell lines relative to their parental WT lines. Venn diagramming revealed
1594 DEGs common to both DoxR cell lines relative to their parental cell lines.
Network analysis pointed to several significantly upregulated epithelial-to
mesenchymal transition pathways, through TGF-beta pathways via RhoA, PI3K, and
ILK and via SMADs, as well as via notch signaling pathways. DoxR cell lines
displayed a more invasive phenotype than respective WT cell lines. CONCLUSIONS:
Human SK-N-SH and SK-N-BE(2)C NB cells display characteristics of mesenchymal
change via multiple pathways in the transition to a drug-resistant state.
PMID- 25128387
TI - Vagal nerve stimulation blocks interleukin 6-dependent synaptic hyperexcitability
induced by lipopolysaccharide-induced acute stress in the rodent prefrontal
cortex.
AB - The ratio between synaptic inhibition and excitation (sI/E) is a critical factor
in the pathophysiology of neuropsychiatric disease. We recently described a
stress-induced interleukin-6 dependent mechanism leading to a decrease in sI/E in
the rodent temporal cortex. The aim of the present study was to determine whether
a similar mechanism takes place in the prefrontal cortex, and to elaborate
strategies to prevent or attenuate it. We used aseptic inflammation (single acute
injections of lipopolysaccharide, LPS, 10mg/kg) as stress model, and patch-clamp
recording on a prefrontal cortical slice preparation from wild-type rat and mice,
as well as from transgenic mice in which the inhibitor of IL-6 trans-signaling
sgp130Fc was produced in a brain-specific fashion (sgp130Fc mice). The anti
inflammatory reflex was activated either by vagal nerve stimulation or peripheral
administration of the nicotinic alpha7 receptor agonist PHA543613. We found that
the IL-6-dependent reduction in prefrontal cortex synaptic inhibition was blocked
in sgp130Fc mice, or - in wild-type animals - upon application sgp130Fc. Similar
results were obtained by activating the "anti-inflammatory reflex" - a neural
circuit regulating peripheral immune response - by stimulation of the vagal nerve
or through peripheral administration of the alpha7 nicotinic receptor agonist
PHA543613. Our results indicate that the prefrontal cortex is an important
potential target of IL-6 mediated trans-signaling, and suggest a potential new
avenue in the treatment of a large class of hyperexcitable neuropsychiatric
conditions, including epilepsy, schizophrenic psychoses, anxiety disorders,
autism spectrum disorders, and depression.
PMID- 25128390
TI - The first report of Telomerina flavipes (Meigen, 1830) (Diptera, Sphaeroceridae)
in a forensic case, with redescription of its pupa.
AB - This paper presents a forensic investigation that took place in the city of
Murcia (SE Spain) and shows how the entomological specimens collected at the
scene were extremely helpful for estimating the minimum post-mortem interval
(PMImin). The occurrence of Telomerina flavipes (Meigen, 1830) (Diptera:
Sphaeroceridae) is reported here for the first time in a forensic case.
Additionally, the importance of other entomological evidence in this case is
discussed. The first known images of the puparium are provided, as well as its
redescription and that of the cephalopharyngeal skeleton recovered from the
puparium.
PMID- 25128388
TI - Structural insights into +1 frameshifting promoted by expanded or modification
deficient anticodon stem loops.
AB - Maintenance of the correct reading frame on the ribosome is essential for
accurate protein synthesis. Here, we report structures of the 70S ribosome bound
to frameshift suppressor tRNA(SufA6) and N1-methylguanosine at position 37
(m(1)G37) modification-deficient anticodon stem loop(Pro), both of which cause
the ribosome to decode 4 rather than 3 nucleotides, resulting in a +1 reading
frame. Our results reveal that decoding at +1 suppressible codons causes
suppressor tRNA(SufA6) to undergo a rearrangement of its 5' stem that
destabilizes U32, thereby disrupting the conserved U32-A38 base pair.
Unexpectedly, the removal of the m(1)G37 modification of tRNA(Pro) also disrupts
U32-A38 pairing in a structurally analogous manner. The lack of U32-A38 pairing
provides a structural correlation between the transition from canonical
translation and a +1 reading of the mRNA. Our structures clarify the molecular
mechanism behind suppressor tRNA-induced +1 frameshifting and advance our
understanding of the role played by the ribosome in maintaining the correct
translational reading frame.
PMID- 25128391
TI - Antiviral efficacy analysis of telbivudine concurrent with the first cycle of
chemotherapy in HBsAg-positive lymphoma patients.
AB - BACKGROUND: HBV reactivation is a common complication in HBsAg-positive lymphoma
patients with chemotherapy or immunotherapy. There is no standard antiviral
treatment for these patients undergoing chemotherapy or immunotherapy. The
initial time, the agent and the duration time are confused at present. OBJECTIVE:
This study aimed to investigate the antiviral efficacy of telbivudine concurrent
with initiation of chemotherapy in HBsAg-positive patients with lymphoma. STUDY
DESIGN: Between April 2008 and October 2012, 359 patients with pathological
diagnoses of lymphoma were admitted to the hospital. Among those, a cohort of 60
HBsAg-positive cases were included in this retrospective study, and telbivudine
was taken at the same day or one day prior to the first cycle of chemotherapy.
The rates of HBV reactivation, virological response, undetectable HBV DNA, the
relationship between HBV reactivation and its clinical characteristics were
investigated. RESULTS: The rate of HBV reactivation was 11.7% (7/60), while it
was 17.5% (7/40) and 75% (3/4) in patients treated with rituximab based
chemotherapy and rituximab maintenance therapy, respectively. The fulminant
hepatitis rate was 6.6%. The rates of virological response, undetectable HBV DNA
and ALT normalization were 88.3%, 61.7% and 83.3%, respectively. HBV reactivation
was associated with rituximab (P = 0.013), and HBeAg-negativity (P = 0.016), but
not correlated with age, gender, clinical stages, extranodal disease, bone marrow
involvement, B symptoms, HBV viral loads or serum LDH level. CONCLUSION:
Concurrent telbivudine treatment with initial chemotherapy can effectively reduce
HBV reactivation in HBsAg-positive lymphoma patients, and the efficacy is
independent of the baseline HBV viral loads.
PMID- 25128392
TI - Vibration transmission to lower extremity soft tissues during whole-body
vibration.
AB - In order to evaluate potential risks of whole-body vibration (WBV) training, it
is important to understand the transfer of vibrations from the WBV platform to
the muscles. Therefore, the purpose of this study was to quantify the
transmissibility of vibrations from the WBV platform to the triceps surae and
quadriceps soft tissue compartments. Sixteen healthy, male participants were
exposed to side-altering WBV at 2.5mm amplitude and frequencies of 10, 17 and 28
Hz. Acceleration signals were measured at the platform and at the soft tissue
compartments using tri-axial accelerometers. Transmissibility of peak
acceleration and peak amplitude for both tested soft tissue compartments was high
at 10 Hz (2.1-2.3), moderate at 17 Hz (1.1-1.9) and low at 28 Hz (0.5-1.2). The
average peak acceleration was 125.4 ms(-2) and 46.5 ms(-2) for the triceps surae
and quadriceps at 28 Hz, respectively. The muscles' vibration frequency was equal
to the input frequency of the WBV platform (p<0.05). The transfer of vibrations
to the muscles is strongly dependent on the platform frequency and the particular
muscle of interest. The acceleration measured at the triceps surae was higher
than the corresponding accelerations related to soft tissue injury in animal
studies but neither existing regulations nor the comparison to available animal
studies seem appropriate to make inferences on injury risk. More realistic animal
or computational muscle models may use the current data to evaluate potentially
unwanted side effects of WBV training.
PMID- 25128394
TI - [Professional politics - for our patients?].
PMID- 25128393
TI - Pulmonary artery relative area change is inversely related to ex vivo measured
arterial elastic modulus in the canine model of acute pulmonary embolization.
AB - A low relative area change (RAC) of the proximal pulmonary artery (PA) over the
cardiac cycle is a good predictor of mortality from right ventricular failure in
patients with pulmonary hypertension (PH). The relationship between RAC and local
mechanical properties of arteries, which are known to stiffen in acute and
chronic PH, is not clear, however. In this study, we estimated elastic moduli of
three PAs (MPA, LPA and RPA: main, left and right PAs) at the physiological state
using mechanical testing data and correlated these estimated elastic moduli to
RAC measured in vivo with both phase-contrast magnetic resonance imaging (PC-MRI)
and M-mode echocardiography (on RPA only). We did so using data from a canine
model of acute PH due to embolization to assess the sensitivity of RAC to changes
in elastic modulus in the absence of chronic PH-induced arterial remodeling. We
found that elastic modulus increased with embolization-induced PH, presumably a
consequence of increased collagen engagement, which corresponds well to decreased
RAC. Furthermore, RAC was inversely related to elastic modulus. Finally, we found
MRI and echocardiography yielded comparable estimates of RAC. We conclude that
RAC of proximal PAs can be obtained from either MRI or echocardiography and a
change in RAC indicates a change in elastic modulus of proximal PAs detectable
even in the absence of chronic PH-induced arterial remodeling. The correlation
between RAC and elastic modulus of proximal PAs may be useful for prognoses and
to monitor the effects of therapeutic interventions in patients with PH.
PMID- 25128399
TI - [Differential diagnosis of hematuria].
AB - Hematuria is the main symptom of many urological and nephrological diseases. In
the differential diagnostics a distinction is made between painful and pain-free
and between macrohematuria which is visible to the naked eye and microhematuria
which is not visible. The reasons for hematuria are basically renal (glomerular)
and non-renal (non-glomerular) causes. In order not to overlook early symptoms of
malignant and relevant benign diseases and also to avoid excessive diagnostic
tests, a differentiated approach is necessary.
PMID- 25128395
TI - [Certification system in urological healthcare : a professional political
evaluation].
AB - There have been function and organ-related certification systems in urology for a
long time. The aim of such certificates is the optimization of patient care above
the defined minimum standards and intensification of interdisciplinary
cooperation. Whether such certificates have led to better patient care has not
been proven. The obligatory documentation in epidemiological cancer registries,
which has been taken up by legislature, will in future lead to so-called clinical
cancer registries in which the complete course of treatment must be entered. With
these registries the quality of healthcare can be compared between individual
institutions. Until now, quality of care data outside oncology are lacking.
Urology would also benefit from a registry with quality of care data for these
patients.
PMID- 25128400
TI - National trends and disparities in cervical cancer screening among commercially
insured Women, 2001-2010.
AB - BACKGROUND: Previous surveys reported declining cervical cancer screening rates
from 2000 to 2010, but trends by key demographic and age groups are less clear.
METHODS: We examined 3-year Papanicolaou (Pap) test rates among 4.2 million women
enrolled in a large national health plan during 2001 to 2010. We calculated and
plotted adjusted 3-year rates stratified by age and key neighborhood-level
socioeconomic characteristics including poverty level and race/ethnicity (white,
black, Hispanic, and mixed ethnicity neighborhood). We fitted trends in 2001-2010
screening rates and socioeconomic disparities as annual percentage changes (APC)
using joinpoint analysis. RESULTS: Women ages 21 to 29 years had estimated 3-year
Pap testing rates of 81.3% to 81.4% over the decade. Estimated disparities by low
high poverty level were 3.1% and 2.0% in 2001-2003 and 2008-2010, respectively, a
nonsignificant decline. Initial white-black disparities were 4.0% and declined
significantly from 2005-2007 to 2008-2010 to 2.8% at an APC of -0.65% (P =
0.021). White-Hispanic disparities declined from 4.3% to 0.8% over the decade, a
0.50% APC (P = 0.024). Among women ages 30 to 64 years, estimated 3-year Pap
testing rates trended down from 76.1% to 71.8% over the decade [-0.94% APC (P <
0.001) until 2005-2007]. This pattern was similar among women from most
categories of poverty and race/ethnicity. CONCLUSIONS: Among commercially insured
women ages 21 to 29 years, 3-year Pap testing rates remained stable at 81% over
the decade; disparities were small and improved for Hispanic women to a greater
degree than for black women. Among women ages 30 to 64 years, 3-year Pap testing
rates declined from 2001 to 2010. IMPACT: Cervical cancer screening should be
promoted to achieve Healthy People 2020 goals.
PMID- 25128401
TI - Smoking at diagnosis is an independent prognostic factor for cancer-specific
survival in head and neck cancer: findings from a large, population-based study.
AB - BACKGROUND: Some studies suggest smoking may result in poorer clinical outcomes
in head and neck cancer, but the evidence is heterogeneous and some of it is poor
quality. In a large, population-based, study we investigated: (i) whether smoking
at diagnosis is an independent prognostic factor for cancer-specific survival in
head and neck cancer; and (ii) whether the association varies by site and
treatment. METHODS: Head and neck cancers (ICD10 C01-C14, and C30-32) diagnosed
from 1994 to 2009 were abstracted from the National Cancer Registry Ireland, and
classified by smoking status at diagnosis. Follow-up was for 5 years or until
December 31, 2010. Multivariate Cox proportional hazards models were used to
compare cancer-specific death rates in current, ex-, and never smokers. Subgroup
analyses by site and treatment were conducted. RESULTS: In total, 5,652 head and
neck cancers were included. At diagnosis, 24% were never smokers, 20% ex-smokers,
and 56% current smokers. Compared with never smokers, current smokers had a
significantly raised death rate from cancer [multivariate HR, 1.36; 95%
confidence interval (CI), 1.21-1.53]. The association was similar after
restriction to squamous cell tumors. A significantly increased cancer-related
death rate was seen for current smokers with oral cavity, pharyngeal, and
laryngeal cancers. The association was stronger in surgically treated patients
[HR, 1.49; 95% CI, 1.25-1.79; P(interaction) = 0.01]. Neither radiotherapy nor
chemotherapy modified the effect of smoking. CONCLUSIONS: Patients with head and
neck cancer who smoke at diagnosis have a significantly increased cancer death
rate. IMPACT: Greater efforts are needed to encourage and support smoking
cessation in those at risk of, and diagnosed with, head and neck cancer.
PMID- 25128402
TI - Improved stool DNA integrity method for early colorectal cancer diagnosis.
AB - BACKGROUND: DNA integrity analysis could represent an alternative approach to the
early detection of colorectal cancer. Previously, fluorescence long DNA (FL-DNA)
in stools was extracted using a manual approach and analyzed by capillary
electrophoresis assay (CE FL-DNA). We aimed to improve diagnostic accuracy using
a simpler and more standardized method [Real Time PCR FL-DNA (RT FL-DNA)] for the
detection of early malignant lesions in a population undergoing colorectal cancer
screening. METHODS: From 241 stool samples, DNA was extracted using manual and
semiautomatic extraction systems and analyzed using FL-DNA tests by CE and RT
assays. The RT FL-DNA approach showed slightly higher sensitivity and specificity
compared with the CE FL-DNA method. Furthermore, we compared the RT FL-DNA
approach with the iFOBT report. RESULTS: Nonparametric ranking statistics were
used to analyze the relationship between the median values of RT FL-DNA and the
clinicohistopathologic characteristics. The median values of both variables were
significantly higher in patients with cancer than in patients with noncancerous
lesions. According to the Fagan nomogram results, the iFOBT and FL-DNA methods
provided more accurate diagnostic information and were able to identify subgroups
at varying risks of cancer. CONCLUSIONS: The combination of the semiautomatic
extraction system and RT FL-DNA analysis improved the quality of DNA extracted
from stool samples. IMPACT: RT FL-DNA shows great potential for colorectal cancer
diagnosis as it is a reliable and relatively easy analysis to perform on
routinely processed stool samples in combination with iFOBT.
PMID- 25128403
TI - Prospective study of seroreactivity to JC virus T-antigen and risk of colorectal
cancers and adenomas.
AB - John Cunningham virus (JCV) is a common polyomavirus classified as a possible
carcinogen by the International Agency for Research on Cancer. JCV may play a
role in colorectal carcinogenesis, although we previously reported no association
between JCV capsid antibodies and colorectal cancer. No studies have examined the
role of seroreactivity to JCV T-antigen (T-Ag) oncoprotein in colorectal cancer.
A case-control study nested within a community-based prospective cohort (CLUE II)
was conducted. In 1989, 25,080 residents of Washington County, Maryland, were
enrolled in CLUE II, completing baseline questionnaires and providing blood
samples. At follow-up, 257 incident colorectal cancer cases were identified by
linkage to population-based cancer registries through 2006 and matched to
controls on age, sex, race, and date of blood draw. One hundred and twenty-three
colorectal adenoma cases were identified through self-report during follow-up and
matched to controls on age, sex, race, date of blood draw, and colorectal cancer
screening. Baseline serum samples were tested for seroreactivity to JCV T-Ag.
Associations between JCV T-Ag seroreactivity and colorectal cancer/adenomas were
evaluated using conditional logistic regression models. Overall, seroreactivity
to JCV T-Ag was not statistically significantly associated with the risk of
either colorectal cancer [OR, 1.34; 95% confidence interval (CI), 0.89-2.01] or
adenoma (OR, 1.30; 95% CI, 0.70-2.42), while a borderline association with
colorectal cancer was observed among women (OR, 1.82; 95% CI, 1.00-3.31). Our
past evaluation of JCV capsid seropositivity, combined with current findings,
does not support a notable etiologic role for JCV infection in colorectal cancer.
PMID- 25128404
TI - Increased intrathoracic and hepatic visceral adipose tissue independently
correlates with coronary artery calcification in asymptomatic patients.
AB - BACKGROUND: Visceral adipose tissue (VAT) is associated with cardiac events, but
it is not clear which, if any of the various measures of VAT independently
correlate with coronary artery disease (CAD). METHODS: We studied 400 patients
undergoing computed tomography to determine coronary artery calcium (CAC) score.
VAT was measured in the form of epicardial adipose tissue (EAT) volume and
thickness, intrathoracic adipose tissue volume (ITAV), and hepatic steatosis.
RESULTS: Of the 400 subjects, the average CAC score was 112.2 +/- 389.3. When
each measure of VAT (EAT volume and thickness, ITAV, hepatic steatosis) was added
to the traditional model (they were independently associated with greater risk of
CAC score >=100 AU as measured by IDI/NRI (P < .05). On univariable logistic
regression analysis, each of the 4 measures of VAT showed association with
greater risk of a CAC score of >=100 AU (OR > 1). CONCLUSIONS: Each measure of
VAT is a strong correlate of CAC score >=100 AU in asymptomatic subjects-these
VAT assessments correlate more significantly than do traditional CAD risk
factors. This incremental power in the predictive models is likely the result of
measurement of a fundamental expression of the metabolic syndrome and consequent
proatherogenic derangements.
PMID- 25128405
TI - Characterisation of novel microRNAs in the Black flying fox (Pteropus alecto) by
deep sequencing.
AB - BACKGROUND: Bats are a major source of new and emerging viral diseases. Despite
the fact that bats carry and shed highly pathogenic viruses including Ebola,
Nipah and SARS, they rarely display clinical symptoms of infection. Host factors
influencing viral replication are poorly understood in bats and are likely to
include both pre- and post-transcriptional regulatory mechanisms. MicroRNAs are a
major mechanism of post-transcriptional gene regulation, however very little is
known about them in bats. RESULTS: This study describes 399 microRNAs identified
by deep sequencing of small RNA isolated from tissues of the Black flying fox,
Pteropus alecto, a confirmed natural reservoir of the human pathogens Hendra
virus and Australian bat lyssavirus. Of the microRNAs identified, more than 100
are unique amongst vertebrates, including a subset containing mutations in
critical seed regions. Clusters of rapidly-evolving microRNAs were identified, as
well as microRNAs predicted to target genes involved in antiviral immunity, the
DNA damage response, apoptosis and autophagy. Closer inspection of the predicted
targets for several highly supported novel miRNA candidates suggests putative
roles in host-virus interaction. CONCLUSIONS: MicroRNAs are likely to play major
roles in regulating virus-host interaction in bats, via dampening of inflammatory
responses (limiting the effects of immunopathology), and directly limiting the
extent of viral replication, either through restricting the availability of
essential factors or by controlling apoptosis. Characterisation of the bat
microRNA repertoire is an essential step towards understanding transcriptional
regulation during viral infection, and will assist in the identification of
mechanisms that enable bats to act as natural virus reservoirs. This in turn will
facilitate the development of antiviral strategies for use in humans and other
species.
PMID- 25128406
TI - The role of VEGF-A165b in trophoblast survival.
AB - BACKGROUND: Pre-eclampsia remains a dominant cause of maternal and fetal
mortality in developed countries. In a previous prospective study we identified a
fall in the VEGF-A isoform VEGF-A165b in the plasma of patients in the first
trimester to be a predictor of later pre-eclampsia. VEGF-A165b has been shown to
have potent cytoprotective properties in many cell types. We therefore tested the
hypothesis that VEGF-A165b may be cytoprotective for placental trophoblasts.
METHODS: We used an immortalised first trimester trophoblast cell line exposed to
chemical toxicity, and physiological (<2% O2) and atmospheric oxygen (21% O2) in
the presence or absence of VEGF-A165b, angiogenic VEGF-A165a, a non-specific anti
VEGF-A blocking antibody (bevacizumab), or a specific anti-VEGF-A165b antibody.
Cell viability and cytotoxicity were measured by trypan blue and LDH assay
respectively. RESULTS: Under high (21%) levels of oxygen, trophoblast viability
was increased, and cytotoxicity reduced by exogenous recombinant VEGF-A165b (p <
0.05, n = 10) or VEGF-A165a. The cytoprotective effect was not seen under lower
(<2%) oxygen conditions, where VEGF-A165b was upregulated. However inhibition of
VEGF-A with blocking antibodies (bevacizumab or anti-VEGF-A165b) had marked
cytotoxic effects under low oxygen conditions presumably through the blockade of
autocrine survival pathways. CONCLUSIONS: These results show that when
trophoblasts are exposed to lower oxygen tensions (as they are early in the 1st
trimester) endogenous VEGF-A165b contributes to their survival through an
autocrine pathway. In contrast in high oxygen conditions exogenous VEGF-A
isoforms have a greater effect on trophoblast survival.
PMID- 25128407
TI - Quantitation of substitutions at amino acid 70 in hepatitis C virus genotype 1b.
AB - BACKGROUND: Substitutions of amino acid (aa) 70 in the core region of hepatitis C
virus genotype 1b (HCV 1b) are a predictor of the non-virological response to
pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy. The aim of our study
was to develop quantitative real-time reverse transcription polymerase chain
reaction (qPCR) assays to quantify wild-type (70 W) and mutant (70 M) strains of
HCV 1b. METHODS: We used the TaqMan system to quantify strains 70 W and 70 M.
Codon 70 in the HCV 1b core region can be either CGN or CAN, therefore degenerate
TaqMan minor groove binder (MGB) probes with inosine were used. We determined
detection limits, sensitivity and specificity of the methods developed. Direct
sequencing and cloning of the HCV core region were used to confirm the
reliability of our new system. Serum samples from 138 Chinese patients infected
with HCV 1b were examined with the system we developed and compared with results
obtained from the Roche TaqMan RT-PCR HCV RNA quantitation system. RESULTS:
Degenerate MGB probes were able to clearly distinguish 70 W from 70 M. The
detection limit was 103 copies/mL. Cross-reactivity tests confirmed the
specificity of our method. Our system can effectively quantify 70 W and 70 M for
99.6% of patients with HCV 1b. Further tests involving cloning and sequencing
confirmed the reliability of our system. CONCLUSIONS: We developed an assay
system using degenerate TaqMan MGB probes with inosine to quantify wild-type and
mutant viral RNAs of the HCV 1b core region at aa 70. Our developed assay system
had high levels of sensitivity and accuracy, and could prove useful in
investigating dynamic changes during PEG-IFN/RBV therapy to assess virological
responses.
PMID- 25128408
TI - Multidimensional complexities of filariasis control in an era of large-scale mass
drug administration programmes: a can of worms.
AB - The impact of control and elimination programmes by mass drug administration
(MDA) targeting onchocerciasis and lymphatic filariasis (LF) in sub-Saharan
Africa over the last two decades has resulted in significantly reduced prevalence
and intensity of infection, with some areas interrupting transmission. However,
given that these infections are often co-endemic and the drugs (either ivermectin
alone or combined with albendazole) also impact on soil transmitted helminths
(STH), the importance of this, in terms of reaching the global goals has not been
assessed. The additional problem posed by Loa loa, where ivermectin cannot be
safely administered due to the risk of serious adverse events compounds this
situation and has left populations drug naive and an alternative strategy to
eliminate LF is yet to be initiated at scale. Here, we present a series of
operational research questions, which must be addressed if the effectiveness of
integrated control of filarial and helminth infections is to be understood for
the endgame. This is particularly important in the diverse and dynamic
epidemiological landscape, which has emerged as a result of the long-term large
scale mass drug administration (or not). There is a need for a more holistic
approach to address these questions. Different programmes should examine this
increased complexity, given that MDA has multiple impacts, drugs are given over
different periods, and programmes have different individual targets.
PMID- 25128409
TI - Unconstrained snoring detection using a smartphone during ordinary sleep.
AB - BACKGROUND: Snoring can be a representative symptom of a sleep disorder, and thus
snoring detection is quite important to improving the quality of an individual's
daily life. The purpose of this research is to develop an unconstrained snoring
detection technique that can be integrated into a smartphone application. In
contrast with previous studies, we developed a practical technique for snoring
detection during ordinary sleep by using the built-in sound recording system of a
smartphone, and the recording was carried out in a standard private bedroom.
METHOD: The experimental protocol was designed to include a variety of actions
that frequently produce noise (including coughing, playing music, talking, rining
an alarm, opening/closing doors, running a fan, playing the radio, and walking)
in order to accurately recreate the actual circumstances during sleep. The sound
data were recorded for 10 individuals during actual sleep. In total, 44 snoring
data sets and 75 noise datasets were acquired. The algorithm uses formant
analysis to examine sound features according to the frequency and magnitude.
Then, a quadratic classifier is used to distinguish snoring from non-snoring
noises. Ten-fold cross validation was used to evaluate the developed snoring
detection methods, and validation was repeated 100 times randomly to improve
statistical effectiveness. RESULTS: The overall results showed that the proposed
method is competitive with those from previous research. The proposed method
presented 95.07% accuracy, 98.58% sensitivity, 94.62% specificity, and 70.38%
positive predictivity. CONCLUSION: Though there was a relatively high false
positive rate, the results show the possibility for ubiquitous personal snoring
detection through a smartphone application that takes into account data from
normally occurring noises without training using preexisting data.
PMID- 25128411
TI - Can a tailored exercise and home hazard reduction program reduce the rate of
falls in community dwelling older people with cognitive impairment: protocol
paper for the i-FOCIS randomised controlled trial.
AB - BACKGROUND: The rate of falls in community dwelling older people with cognitive
impairment (CI) is twice that of a cognitively intact population, with almost two
thirds of people with CI falling annually. Studies indicate that exercise
involving balance and/or a home hazard reduction program are effective in
preventing falls in cognitively intact older people. However the potential
benefit of these interventions in reducing falls in people with CI has not been
established.This randomised controlled trial will determine whether a tailored
exercise and home hazard reduction program can reduce the rate of falls in
community dwelling older people with CI. We will determine whether the
intervention has beneficial effects on a range of physical and psychological
outcome measures as well as quality of life of participants and their carers. A
health economic analysis examining the cost and potential benefits of the program
will also be undertaken. METHODS AND DESIGN: Three hundred and sixty people aged
65 years or older living in the community with CI will be recruited to
participate in the trial. Each will have an identifiable carer with a minimum of
3.5 hours of face to face contact each week.Participants will undergo an
assessment at baseline with retests at 6 and 12 months. Participants allocated to
the intervention group will participate in an exercise and home hazard reduction
program tailored to their cognitive and physical abilities.The primary outcome
measure will be the rate of falls which will be measured using monthly falls
calendars. Secondary outcome measures will include the risk of falling, quality
of life, measures of physical and cognitive function, fear of falling and planned
and unplanned use of health services. Carers will be followed up to determine
carer burden, coping strategies and quality of life. DISCUSSION: The study will
determine the impact of this tailored intervention in reducing the rate of falls
in community dwelling older people with CI as well as the cost-effectiveness and
adherence to the program. The results will have direct implications for the
design and implementation of interventions for this high-risk group of older
people. TRIAL REGISTRATION: The protocol for this study is registered with the
Australian New Zealand Clinical Trials Registry - ACTRN12614000603617.
PMID- 25128410
TI - Activated microglia contribute to neuronal apoptosis in Toxoplasmic encephalitis.
AB - BACKGROUND: A plethora of evidence shows that activated microglia play a critical
role in the pathogenesis of the central nervous system (CNS). Toxoplasmic
encephalitis (TE) frequently occurs in HIV/AIDS patients. However, knowledge
remains limited on the contributions of activated microglia to the pathogenesis
of TE. METHODS: A murine model of reactivated encephalitis was generated in a
latent infection with Toxoplasma gondii induced by cyclophosphamide. The neuronal
apoptosis in the CNS and the profile of pro-inflammatory cytokines were assayed
in both in vitro and in vivo experiments. RESULTS: Microglial cells were found to
be activated in the cortex and hippocampus in the brain tissues of mice. The in
vivo expression of interleukin-6 (IL-6), interleukin-1beta (IL-1beta), tumor
necrosis factor-alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS)
were up-regulated in TE mice, and accordingly, the neuronal apoptosis was
significantly increased. The results were positively correlated with those of the
in vitro experiments. Additionally,apoptosis of the mouse neuroblastoma type
Neuro2a (N2a) remarkably increased when the N2a was co-cultured in transwell with
microglial cells and Toxoplasma tachyzoites. Both in vivo and in vitro
experiments showed that minocycline (a microglia inhibitor) treatment notably
reduced microglial activation and neuronal apoptosis. CONCLUSIONS: Activated
microglia contribute to neuronal apoptosis in TE and inhibition of microglia
activation might represent a novel therapeutic strategy of TE.
PMID- 25128412
TI - Barriers to sight impairment certification in the UK: the example of a population
with diabetes in East London.
AB - BACKGROUND: This study assessed the barriers to sight impairment certification in
the East London Borough of Tower Hamlets amongst patients attending the Diabetic
Retinopathy Screening Service (DRSS). METHODS: All patients who attended DRSS
between 1stApril 2009 and 31st of March 2010 and whose recorded best corrected
visual acuity (BCVA) at DRSS fulfilled the requirements for sight impairment in
the UK were included. An additional 24 patients whose general practitioners (GPs)
reported them to be certified blind due to no perception of light (NPL) vision
were re-examined to ascertain the reason for certification, and their potential
social and visual aids needs. RESULTS: 78 patients were identified with
certifiable vision and were reviewed: 10 deceased in the preceding 12 months; 60
were not known to be certified. Of these, 57 attended further assessment, 27 were
found to have non-certifiable vision, 9 were referred for further interventions,
9 were certified and 9 were found to be eligible, but declined certification.
Five patients were registered due to diabetic eye disease.Of those 24 reported by
the GP of NPL vision, only 4 had true NPL, the rest had usable vision. Only two
of them were certified blind due to diabetes. CONCLUSIONS: Our data shows that
sight certification in patients with diabetes might be underestimated and these
patients often have non-diabetes related visual loss. We propose that data on
certifiable visual impairment could serve, along with existing certification
databases, as a resource for quality of care standards assessment and service
provision for patients with diabetes.
PMID- 25128413
TI - Change in abortion services after implementation of a restrictive law in Texas.
AB - OBJECTIVES: In 2013, Texas passed omnibus legislation restricting abortion
services. Provisions restricting medical abortion, banning most procedures after
20 weeks and requiring physicians to have hospital-admitting privileges were
enforced in November 2013; by September 2014, abortion facilities must meet the
requirements of ambulatory surgical centers (ASCs). We aimed to rapidly assess
the change in abortion services after the first three provisions went into
effect. STUDY DESIGN: We requested information from all licensed Texas abortion
facilities on abortions performed between November 2012 and April 2014, including
the abortion method and gestational age (< 12 weeks vs. >= 12 weeks). RESULTS: In
May 2013, there were 41 facilities providing abortion in Texas; this decreased to
22 in November 2013. Both clinics closed in the Rio Grande Valley, and all but
one closed in West Texas. Comparing November 2012-April 2013 to November 2013
April 2014, there was a 13% decrease in the abortion rate (from 12.9 to 11.2
abortions/1000 women age 15-44). Medical abortion decreased by 70%, from 28.1% of
all abortions in the earlier period to 9.7% after November 2013 (p<0.001). Second
trimester abortion increased from 13.5% to 13.9% of all abortions (p<0.001). Only
22% of abortions were performed in the state's six ASCs. CONCLUSIONS: The closure
of clinics and restrictions on medical abortion in Texas appear to be associated
with a decline in the in-state abortion rate and a marked decrease in the number
of medical abortions. IMPLICATIONS: Supply-side restrictions on abortion -
especially restrictions on medical abortion - can have a profound impact on
access to services. Access to abortion care will become even further restricted
in Texas when the ASC requirement goes into effect in 2014.
PMID- 25128414
TI - Management of the open abdomen using vacuum-assisted wound closure and mesh
mediated fascial traction.
AB - BACKGROUND: The open abdomen has become an accepted treatment option of
critically ill patients with severe intra-abdominal conditions. Fascial closure
is a particular challenge in patients with peritonitis. This study investigates
whether fascial closure rates can be increased in peritonitis patients by using
an algorithm that combines vacuum-assisted wound closure and mesh-mediated
fascial traction. Moreover, fascial closure rates for patients with peritonitis,
trauma or abdominal compartment system (ACS) are compared. METHODS: Data were
collected prospectively from all patients who underwent open abdomen management
at our institution from 2006 to 2012. All patients were treated under a
standardised algorithm that combines vacuum-assisted closure and mesh placement
at the fascial level. RESULTS: During the study period, 53 patients (mean age 53
years) underwent open abdomen management for a mean duration of 15 days.
Indications for leaving the abdomen open were peritonitis (51 %), trauma (26 %),
and ACS or abdominal wall dehiscence (23 %). The fascial closure rate was 79 % in
an intention-to-treat analysis and 89 % in a per-protocol analysis. Mortality was
13 %. No patient developed an enteroatmospheric fistula or abdominal wall
dehiscence after closure. The mean duration of treatment was significantly longer
in peritonitis patients (20 days) than in patients without peritonitis (10 days)
(p = 0.03). There were no significant differences in fascial closure rates
between patients with peritonitis (87 %), trauma (85 %), and ACS or abdominal
wall dehiscence (100 %) (p = 0.647). CONCLUSIONS: Regardless of the underlying
pathology, high fascial closure rates can be achieved using a combination of
vacuum-assisted closure and mesh-mediated fascial traction.
PMID- 25128415
TI - Heteronormativity and sexual partnering among bisexual Latino men.
AB - Our analyses address the question of how bisexual Latino men organize their
sexual partnerships. Heteronormativity can be understood as the set of social
norms and normative structures that guide sexual partnering among men and women.
We provide descriptive statistics to describe bisexual Latino men's sexual
partnerships. Logistic and linear regression modeling were used to explore
bivariate and multivariate relationships. Of our total sample (N = 142), 41.6 %
had unprotected vaginal intercourse 2 months prior to the interview; 21.8 % had
unprotected anal intercourse with female partners; 37.5 % had unprotected
insertive anal intercourse with male partners; and 22.5 % had unprotected
receptive anal intercourse with male partners. In our multivariate model,
machismo was directly associated with meeting female partners through formal
spaces (workplace, school, and/or church), but inversely associated with meeting
male partners in formal spaces. Machismo was positively associated with meeting
male sex partners through social networks (i.e., friendship and kinship
networks). The more comfortable men were with homosexuality the less likely they
were to meet men online and the more likely they were to meet men through social
networks of friends and kinship. Interventions to reduce sexually transmitted
diseases that target bisexual behavior as an epidemiological "bridge" of
transmission from homosexual to heterosexual networks might very well benefit
from a more complex understanding of how Latino bisexuality is patterned. Thus,
this exploratory analysis might lead to a rethinking of how to address risk and
vulnerability among Latino bisexual men and their sexual networks.
PMID- 25128417
TI - Mutations in the 3c and 7b genes of feline coronavirus in spontaneously affected
FIP cats.
AB - Feline infectious peritonitis (FIP) is the most frequent lethal infectious
disease in cats. However, understanding of FIP pathogenesis is still incomplete.
Mutations in the ORF 3c/ORF 7b genes are proposed to play a role in the
occurrence of the fatal FIPV biotype. Here, we investigated 282 tissue specimens
from 28 cats that succumbed to FIP. Within one cat, viral sequences from
different organs were similar or identical, whereas greater discrepancies were
found comparing sequences from various cats. Eleven of the cats exhibited
deletions in the 3c gene, resulting in truncated amino acid sequences. The 7b
gene was affected by deletions only in one cat. In three of the FIP cats,
coronavirus isolates with both intact 3c genes as well as 7b genes of full length
could also be detected. Thus, deletions or stop codons in the 3c sequence seem to
be a frequent but not compelling feature of FIPVs.
PMID- 25128416
TI - Effect of human leukocyte antigen-C and -DQ matching on pediatric heart
transplant graft survival.
AB - BACKGROUND: A higher degree of human leukocyte antigen (HLA) matching at the A,
B, and DR loci has been associated with improved long-term survival after
pediatric heart transplantation in multiple International Society for Heart and
Lung Transplantation registry reports. The aim of this study was to investigate
the association of HLA matching at the C and DQ loci with pediatric graft
survival. METHODS: The United Network of Organ Sharing database was queried for
isolated heart transplants that occurred from 1988 to 2012 with a recipient age
of 17 or younger and at least 1 postoperative follow-up encounter. When HLA
matching at the C or DQ loci were analyzed, only transplants with complete typing
of donor and recipient at the respective loci were included. Transplants were
divided into patients with at least 1 match at the C locus (C-match) vs no match
(C-no), and at least 1 match at the DQ (DQ-match) locus vs no match (DQ-no).
Primary outcome was graft loss. Univariate analysis was performed with the log
rank test. Cox regression analysis was performed with the following patient
factors included in the model: recipient age, ischemic time; recipient on
ventilator, extracorporeal membrane oxygenation, ventricular assist device, or
inotropes at transplant; recipient serum bilirubin and creatinine closest to
transplant, ratio of donor weight to recipient weight, underlying cardiac
diagnosis, crossmatch results, transplant year, and HLA matching at the A, B, and
DR loci. RESULTS: Complete typing at the C locus occurred in 2,429 of 4,731
transplants (51%), and complete typing at the DQ locus occurred in 3,498 of 4,731
transplants (74%). Patient factors were similar in C-match and C-no, except for
year of transplant (median year, 2007 [interquartile range, 1997-2010] vs year
2005 [interquartile range, 1996-2009], respectively; p = 0.03) and the degree of
HLA matching at the A, B, and DR loci (high level of HLA matching in 11.9% vs 3%,
respectively; p < 0.01). Matching at the C locus was not associated with a
decreased risk of graft loss (median graft survival: 13.1 years [95% confidence
interval {CI}, 11.5-14.8] in C-no vs 15.1 years [95% CI, 13.5-16.6) in C-match, p
= 0.44 log-rank; hazard ratio, 0.93; 95% CI, 0.76-1.15; p = 0.52). DQ-match did
not differ from DQ-no in any of the analyzed patient factors, except DQ-match was
more likely to have high degree of matching at the A, B, and DR loci vs DQ-no
(9.8% vs 3.2%, p < 0.01). Matching at the DQ locus was not associated with
decreased risk of graft loss (median graft survival: DQ-no, 13.1 years [95% CI,
11.7-14.6) vs DQ-match, 13.0 years [95% CI, 11.4-14.6], p = 0.80, log-rank;
hazard ratio, 0.95; 95% CI, 0.81-1.1; p = 0.51. CONCLUSIONS: Complete typing at
the C locus of both donor and recipient occurs less often then typing at the DQ
locus. A higher degree of donor-recipient HLA matching at the C locus or the DQ
locus appears not to confer any graft survival advantage.
PMID- 25128418
TI - Involvement of glucagon-like peptide 1 in the glucose homeostasis regulation in
obese and pituitary-dependent hyperadrenocorticism affected dogs.
AB - The incretin glucagon-like peptide 1 (GLP-1) enhances insulin secretion. The aim
of this study was to assess GLP-1, glucose and insulin concentrations,
Homeostatic Model Assessment (HOMA insulin sensitivity and HOMA beta-cell
function) in dogs with pituitary-dependent hyperadrenocorticism (PDH), and
compare these values with those in normal and obese dogs. The Oral Glucose
Tolerance Test was performed and the glucose, GLP-1 and insulin concentrations
were evaluated at baseline, and after 15, 30, 60 and 120 minutes. Both basal
concentration and those corresponding to the subsequent times, for glucose, GLP-1
and insulin, were statistically elevated in PDH dogs compared to the other
groups. Insulin followed a similar behaviour together with variations of GLP-1.
HOMA insulin sensitivity was statistically decreased and HOMA beta-cell function
increased in dogs with PDH. The higher concentrations of GLP-1 in PDH could play
an important role in the impairment of pancreatic beta-cells thus predisposing to
diabetes mellitus.
PMID- 25128419
TI - Increase of multidrug efflux pump expression in fluoroquinolone-resistant
Salmonella mutants induced by ciprofloxacin selective pressure.
AB - Multidrug-resistant foodborne pathogens are a leading public health concern, as
antimicrobial resistance can lead to therapeutic failure. In this study, a
ciprofloxacin-susceptible Salmonella Istanbul (Sal10-FC-KU12) was isolated from
chicken meat obtained from a market in Korea to induce ciprofloxacin-resistant
mutants (SalML, SalMM, and SalMH). Minimum inhibitory concentrations (MICs) of 12
antibiotics were measured in the presence or absence of an efflux pump inhibitor.
Expression levels of efflux pump-related genes (acrB, acrF, marA, ramA, rob, and
soxS) were determined using quantitative reverse transcription polymerase chain
reaction (qRT-PCR). Elevated MICs for the derived mutants were shown to result
from the action of the efflux pump, with increased expression of marA, ramA, and
acrB compared with the wild-type strain. The results of this study suggest that
continued use of ciprofloxacin might induce the emergence of Salmonella mutants
resistant not only to fluoroquinolones, but also to several other classes of
antimicrobials.
PMID- 25128420
TI - Darpp-32 and t-Darpp are differentially expressed in normal and malignant mouse
mammary tissue.
AB - BACKGROUND: Darpp-32 and t-Darpp are expressed in several forms of breast cancer.
Both are transcribed from the gene PPP1R1B via alternative promoters. In humans,
Darpp-32 is expressed in both normal and malignant breast tissue, whereas t-Darpp
has only been found in malignant breast tissue. The exact biological functions of
these proteins in the breast are not known. Although Darpp-32 is a well known
regulator of neurotransmission, its role in other tissues and in cancer is less
well understood. t-Darpp is known to increase cellular growth, inhibit apoptosis
and contribute to acquired drug resistance. The use of transgenic mouse mammary
tumor models to study Darpp-32 and t-Darpp in breast cancer in vivo has been
limited by a lack of knowledge regarding t-Darpp expression in mice, in both
normal and malignant tissue. METHODS: We used RT-PCR and Western analysis to
investigate Darpp-32 and t-Darpp levels in normal and malignant mouse mammary
tissue. To determine if Darpp-32 and t-Darpp play a direct role in mammary tumor
development, Ppp1r1b gene knockout mice and wild-type mice were crossed with a
mouse mammary tumor model. Tumor growth and metastasis were examined. Differences
between groups were determined by the two-tailed Student's t-test. RESULTS: We
found that Darpp-32 was expressed in normal mouse mammary tissue and in some
breast tumors, whereas t-Darpp was found exclusively in tumors, with t-Darpp
usually expressed at equal or higher levels than Darpp-32. Ppp1r1b knockout in
MMTV-PyMT transgenic tumor mice resulted in a decrease in tumor growth.
CONCLUSIONS: The shift in expression from Darpp-32 to t-Darpp during mouse
mammary tumorigenesis is reminiscent of the expression patterns observed in
humans and is consistent with a role for t-Darpp in promoting cell growth and
Darpp-32 in inhibiting cell growth. Decreased tumor growth in Ppp1r1b knockout
mice also suggests that t-Darpp plays a direct role, predominant to Darpp-32, in
mammary tumor development. These results indicate that transgenic mouse mammary
tumor models might be valuable tools for future investigation of Darpp-32 and t
Darpp in breast cancer.
PMID- 25128421
TI - Danish emergency nurses' attitudes towards self-harm - a cross-sectional study.
AB - AIM: The aim of this study was to examine Danish emergency nurses' attitudes
toward people hospitalized after an acetaminophen poisoning. Furthermore, the
study examined the relationship between attitudes and factors such as age,
gender, and education on self-harm. METHODS: A cross-sectional design was
applied. Nurses from seven emergency departments (EDs) in a region in Denmark
were asked to complete the Danish version of Attitudes towards Deliberate Self
Harm Questionnaire (ADSHQ). RESULTS: Of the 254 eligible nurses working in the
ED, 122 returned the questionnaires, leaving the response rate at 48%. Results
show that the emergency nurses generally held positive attitudes toward patients
with acetaminophen poisoning. Nurses with longer ED experience held more positive
attitudes, and women scored significantly higher than men on the whole scale.
Only 19% of the respondents had received education on self-harm, and this
education seems to produce more positive attitudes and a greater self-efficacy in
relation to managing the patient group. CONCLUSION: Nurses working in the ED
generally hold positive attitudes toward patients with acetaminophen poisoning.
It is suggested that education on self-harm is a worthwhile endeavor with the
potential to strengthen and improve attitudes, for the benefit of both the nurses
and the patients.
PMID- 25128422
TI - Coptis chinensis alkaloids exert anti-adipogenic activity on 3T3-L1 adipocytes by
downregulating C/EBP-alpha and PPAR-gamma.
AB - Obesity is a complex, multifactorial, and chronic disease that increases the risk
for type 2 diabetes, coronary heart disease and hypertension, and has become a
major worldwide health problem. Developing novel anti-obesity drugs from natural
products is a promising solution to the global health problem of obesity. While
screening anti-obesity potentials of natural products, the methanol extract of
the rhizome of Coptis chinensis (Coptidis Rhizoma) was found to significantly
inhibit adipocyte differentiation and lipid contents in 3T3-L1 cells, as assessed
by Oil-Red O staining. Five known alkaloids, berberine, epiberberine, coptisine,
palmatine, and magnoflorine, were isolated from the n-BuOH fraction of the
methanol extract of Coptidis Rhizoma. We determined the chemical structure of
these alkaloids through comparisons of published nuclear magnetic resonance (NMR)
spectral data. Furthermore, we screened these alkaloids for their ability to
inhibit adipogenesis over a range of concentrations (12.5-50 MUM). All five
Coptidis Rhizoma alkaloids significantly inhibited lipid accumulation in 3T3-L1
cells without affecting cell viability in a concentration dependent manner. In
addition, the five alkaloids significantly reduced the expression levels of
several adipocyte marker genes including proliferator activated receptor-gamma
(PPAR-gamma) and CCAAT/enhancer-binding protein-alpha (C/EBP-alpha). In the
present study, we found that the isolated alkaloids inhibited adipogenesis in a
dose-dependent manner in 3T3-L1 cells; this inhibition was attributed to their
abilities to downregulate the protein levels of the adipocyte marker proteins
PPAR-gamma and C/EBP-alpha. Thus, these results suggest that Coptidis Rhizoma
extract and its isolated alkaloids may be of therapeutic interest with respect to
the treatment of obesity.
PMID- 25128423
TI - Cytotoxic and anti-inflammatory ent-kaurane diterpenoids from Isodon
wikstroemioides.
AB - Seven new ent-kaurane diterpenoids, isowikstroemins A-G (1-7), were isolated from
EtOAc extracts of the aerial parts of Isodon wikstroemioides. Their structures
were elucidated by extensive spectroscopic analysis. The isolates were evaluated
for their cytotoxicity against five human tumor cell lines, and compounds 1-4
exhibited significant activity with IC50 values ranging from 0.9 to 7.0 MUM. In
addition, compounds 1, 2, 3, 4, and 7 exhibited inhibitory activity against
nitric oxide (NO) production in LPS-activated RAW264.7 macrophages.
PMID- 25128424
TI - The cytotoxic activities of cardiac glycosides from Streptocaulon juventas and
the structure-activity relationships.
AB - A series of cardiac glycosides were isolated and identified from the anti-tumor
fraction of the root of Streptocaulon juventas in previous studies. In the
present research, the cytotoxic activities of the 43 cardiac glycosides on three
cell lines, human lung A549 adenocarcinoma cell, large cell lung cancer NCI-H460
cell and normal human fetal lung fibroblast MRC-5 cell, were evaluated in vitro.
Most of the tested compounds showed potent inhibitory activities toward the three
cell lines. Then, the structure-activity relationships were discussed in detail.
It was indicated that hydroxyl and acetyl groups at C-16 increased the activity,
whereas hydroxyl group at C-1 and C-5 can both increase and decrease the
activity. Two glucosyl groups which were connected by C1'->C6' showed better
inhibitory activity against cancer cell lines, while the C1'->C4' connection
showed stronger inhibitory activity against the normal cell line. Also, this is
the first report that the activities of these compounds exhibited different
variation trends between A549 and NCI-H460 cell lines, which indicated that these
compounds could selectively inhibit the cell growth. The results would lay a
foundation for further research on new anti-tumor drug development.
PMID- 25128425
TI - The therapeutic effects of EGCG on vitiligo.
AB - Epigallocatechin-3-gallate (EGCG) is one of the main chemical constituents of
green tea, which has been used as an important traditional Chinese medicine.
Green tea has anti-inflammatory, anti-oxidant, and immunomodulatory properties.
However, the effects of EGCG on vitiligo are not known. We assessed the role of
EGCG in vitiligo induced by monobenzone in mice. We demonstrated that EGCG:
delayed the time of depigmentation; reduced the prevalence of depigmentation; and
decreased the area of depigmentation. Examination of depigmented skin treated
with EGCG by reflectance confocal microscopy suggested increased numbers of
epidermal melanocytes and histologic examination showed decreased perilesional
accumulation of CD8(+) T cells. To further investigate the mechanism of the anti
inflammatory effects of EGCG, levels of inflammatory mediator tumor necrosis
factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-6 were tested by
enzyme-linked immunosorbent assay. Serum cytokine levels were significantly
decreased after administration of EGCG compared with the model group. These
results suggested that EGCG may have protective effects against vitiligo, and
that it could contribute to suppression of activation of CD8(+) T cells and
inflammatory mediators. Based on these results, 5% EGCG was considered to be the
most suitable concentration for treating vitiligo, and was used for further
study. In addition, we investigated the gene-expression profile of this model in
relation to EGCG. Using a 4*44K whole genome oligo microarray assay, 1264 down
regulated genes and 1332 up-regulated genes were recorded in the 5% EGCG group
compared with the model group, and selected genes were validated by real-time
polymerase chain reaction. Our study demonstrated that EGCG administration was
significantly associated with a decreased risk of vitiligo. EGCG could be a new
preventive agent against vitiligo in the clinical setting.
PMID- 25128426
TI - Chemical constituents of Morus alba L. and their inhibitory effect on 3T3-L1
preadipocyte proliferation and differentiation.
AB - Mulberry leaf, an important traditional Chinese medicine, possesses many
biological activities, including effects of anti-obesity. However, which
constituents of mulberry leaf are responsible for its anti-adipogenic action is
unclear. This study primarily investigated the chemical constituents from
mulberry leaf and their bioactivity on the proliferation and differentiation of
3T3-L1 preadipocytes. A new flavane derivative, (2S)-4'-hydroxy-7-methoxy-8
prenylflavan (1), together with twelve known compounds including three flavanes
(2-4), three chalcones (5-7), two flavones (8-9), two benzofurans (10-11) and two
coumarin (12-13) was isolated from mulberry leaf. The structure of the new
compound was elucidated by various spectroscopic methods including UV, HR-ESI-MS,
(1)H and (13)C NMR and CD. The results of activity screening showed that compound
2, 6 and 7 inhibited the proliferation and differentiation of 3T3-L1
preadipocytes.
PMID- 25128427
TI - Penialidins A-C with strong antibacterial activities from Penicillium sp., an
endophytic fungus harboring leaves of Garcinia nobilis.
AB - Three new polyketides named penialidins A-C (1-3), along with one known compound,
citromycetin (4), were isolated from an endophytic fungus, Penicillium sp.,
harbored in the leaves of the Cameroonian medicinal plant Garcinia nobilis. Their
structures were elucidated by means of spectroscopic and spectrometric methods
(NMR and HRMS(n)). The antibacterial efficacies of the new compounds (1-3) were
tested against the clinically-important risk group 2 (RG2) bacterial strains of
Staphylococcus aureus and Escherichia coli. The ecologically imposing strains of
E. coli (RG1), Bacillus subtilis and Acinetobacter sp. BD4 were also included in
the assay. Compound 3 exhibited pronounced activity against the clinically
relevant S. aureus as well as against B. subtilis comparable to that of the
reference standard (streptomycin). Compound 2 was also highly-active against S.
aureus. By comparing the structures of the three new compounds (1-3), it was
revealed that altering the substitutions at C-10 and C-2 can significantly
increase the antibacterial activity of 1.
PMID- 25128428
TI - Sesterterpenoids and other constituents from Salvia lachnocalyx Hedge.
AB - Three new sesterterpene lactones, lachnocalyxolide A-C [1, 2, and 3 (as epimeric
pair)] together with nine known compounds, including two sesterterpenoids, three
flavonoids, two steroidal compounds, one nor diterpenoid and one triterpenoid,
were isolated from the acetone extract of the aerial parts of Salvia lachnocalyx
Hedge. Their structures were elucidated on the basis of extensive spectroscopic
data, including 1D and 2D NMR spectra, as well as HR-ESI-MS. Compounds 1, 2, 4
and 5 were also tested for their inhibitory activity toward MCF-7 and HeLa cell
lines.
PMID- 25128429
TI - Association between parental guilt and oral health problems in preschool
children: a hierarchical approach.
AB - BACKGROUND: Dental caries and traumatic dental injury (TDI) can play an important
role in the emergence of parental guilt, since parents feel responsible for their
child's health. The aim of the present study was to evaluate the influence of
oral health problems among preschool children on parental guilt. METHODS: A
preschool-based, cross-sectional study was carried out with 832 preschool
children between three and five years of age in the city of Campina Grande,
Brazil. Parents/caregivers answered the Brazilian version of the Early Childhood
Oral Health Impact Scale (B-ECOHIS). The item "parental guilt" was the dependent
variable. Questionnaires addressing socio-demographic variables (child's sex,
child's age, parent's/caregiver's age, mother's schooling, type of preschool and
household income), history of toothache and health perceptions (general and oral)
were also administered. Clinical exams for dental caries and TDI were performed
by three dentists who had undergone a training and calibration exercise (Kappa:
0.85-0.90). Poisson hierarchical regression was used to determine the
significance of associations between parental guilt and oral health problems
(alpha = 5%). The multivariate model was carried out on three levels using a
hierarchical approach from distal to proximal determinants: 1) socio-demographic
aspects; 2) health perceptions; and 3) oral health problems. RESULTS: The
frequency of parental guilt was 22.8%. The following variables were significantly
associated with parental guilt: parental perception of child's oral health as
poor (PR = 2.010; 95% CI: 1.502-2.688), history of toothache (PR = 2.344; 95% CI:
1.755-3.130), cavitated lesions (PR = 2.002; 95% CI: 1.388-2.887),
avulsion/luxation (PR = 2.029; 95% CI: 1.141-3.610) and tooth discoloration (PR =
1.540; 95% CI: 1.169-2.028). CONCLUSION: Based on the present findings, parental
guilt increases with the occurrence of oral health problems that require
treatment, such as dental caries and TDI of greater severity. Parental
perceptions of poor oral health in their children and history of toothache were
predictors of greater feelings of parental guilt.
PMID- 25128430
TI - Absence of an association between anti-Ro antibodies and prolonged QTc interval
in systemic sclerosis: a multicenter study of 689 patients.
AB - OBJECTIVE: To examine the association between anti-Ro antibodies, namely anti
Ro60/SS-A and anti-Ro52/TRIM21, together and separately, and a prolonged QT
interval corrected for heart rate (QTc) in systemic sclerosis (SSc) patients.
METHODS: A total of 689 SSc patients enrolled in a multicenter cohort study
underwent a 12-lead resting EKG at baseline. The QTc interval was measured, and a
QTc >= 440ms was considered prolonged. Detailed clinical data and sera of these
patients were collected and positivity for anti-Ro60/SS-A and anti-Ro52/TRIM21
antibodies was determined using an addressable laser bead immunoassay (ALBIA).
RESULTS: QTc prolongation was common in this SSc cohort (25%). In a univariate
analysis, Ro antibodies, together or separately, were not associated with
prolongation of the QTc interval [mean difference in QTc in anti-Ro antibody
positive versus negative subjects was -2.2ms (p = 0.5748), in anti-Ro60/SS-A
antibody positive versus negative subjects was 1.3ms (p = 0.8616), and in anti
Ro52/TRIM21 antibody positive versus negative subjects was -3.3ms (p = 0.4106)].
In a multivariate logistic regression analysis adjusting for possible
confounders, there was no association between prolonged QTc and anti-Ro
antibodies [odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.45, 1.22],
anti-Ro60/SS-A antibodies (OR = 1.57, 95% CI: 0.72, 3.41), and anti-Ro52/TRIM21
antibodies (OR = 0.76, 95% CI: 0.46, 1.26). However, in both univariate and
multivariate analyses, QTc prolongation was associated with longer disease
duration, greater disease severity, and the presence of anti-RNA polymerase III
antibodies. CONCLUSIONS: QTc prolongation is common in SSc, although anti-Ro
antibodies do not seem to be associated with it as is the case in systemic lupus
erythematosus. The reasons for this difference as well as the cause of
abnormalities in cardiac repolarization in SSc will require additional studies.
PMID- 25128431
TI - Dissociating the influence of response selection and task anticipation on
corticospinal suppression during response preparation.
AB - Motor behavior requires selecting between potential actions. The role of
inhibition in response selection has frequently been examined in tasks in which
participants are engaged in some advance preparation prior to the presentation of
an imperative signal. Under such conditions, inhibition could be related to
processes associated with response selection, or to more general inhibitory
processes that are engaged in high states of anticipation. In Experiment 1, we
manipulated the degree of anticipatory preparation. Participants performed a
choice reaction time task that required choosing between a movement of the left
or right index finger, and used transcranial magnetic stimulation (TMS) to elicit
motor evoked potentials (MEPs) in the left hand agonist. In high anticipation
blocks, a non-informative cue (e.g., fixation marker) preceded the imperative; in
low anticipation blocks, there was no cue and participants were required to
divide their attention between two tasks to further reduce anticipation. MEPs
were substantially reduced before the imperative signal in high anticipation
blocks. In contrast, in low anticipation blocks, MEPs remained unchanged before
the imperative signal but showed a marked suppression right after the onset of
the imperative. This effect occurred regardless of whether the imperative had
signalled a left or right hand response. After this initial inhibition, left MEPs
increased when the left hand was selected and remained suppressed when the right
hand was selected. We obtained similar results in Experiment 2 except that the
persistent left MEP suppression when the left hand was not selected was
attenuated when the alternative response involved a non-homologous effector
(right foot). These results indicate that, even in the absence of an anticipatory
period, inhibitory mechanisms are engaged during response selection, possibly to
prevent the occurrence of premature and inappropriate responses during a
competitive selection process.
PMID- 25128434
TI - Pilot randomized evaluation of publically available concussion education
materials: evidence of a possible negative effect.
AB - Many states and sports leagues are instituting concussion policies aimed at
reducing risk of morbidity and mortality; many include mandates about the
provision of concussion education to youth athletes. However, there is limited
evidence if educational materials provided under these typically vague mandates
are in fact effective in changing concussion risk-related behavior or any
cognition predictive of risk-related behavior. The purpose of this pilot
randomized controlled study was to conduct a theory-driven evaluation of three
publically available concussion education materials: two videos and one
informational handout. Participants were 256 late adolescent males from 12 teams
in a single league of ice hockey competition in the United States. Randomization
of educational condition occurred at the team level. Written surveys assessing
postimpact symptom reporting behavior, concussion knowledge, and concussion
reporting cognitions were completed by participants immediately before receiving
their educational intervention, 1 day after, and 1 month after. Results indicated
no change in any measure over any time interval, with the exception of perceived
underreporting norms. In one of the video conditions, perceived underreporting
norms increased significantly 1 day after viewing the video. Possible content and
viewing environment-related reasons for this increase are discussed. Across all
conditions, perceived underreporting norms increased 1 month after intervention
receipt, raising the possibility that late in the competitive season
underreporting may be perceived as normative. The need for the development of
theory-driven concussion education materials, drawing on best practices from
health behavior scholars, is discussed.
PMID- 25128433
TI - Genetic and molecular identification of three human TPP1 functions in telomerase
action: recruitment, activation, and homeostasis set point regulation.
AB - Telomere length homeostasis is essential for the long-term survival of stem
cells, and its set point determines the proliferative capacity of differentiated
cell lineages by restricting the reservoir of telomeric repeats. Knockdown and
overexpression studies in human tumor cells showed that the shelterin subunit
TPP1 recruits telomerase to telomeres through a region termed the TEL patch.
However, these studies do not resolve whether the TPP1 TEL patch is the only
mechanism for telomerase recruitment and whether telomerase regulation studied in
tumor cells is representative of nontransformed cells such as stem cells. Using
genome engineering of human embryonic stem cells, which have physiological
telomere length homeostasis, we establish that the TPP1 TEL patch is genetically
essential for telomere elongation and thus long-term cell viability. Furthermore,
genetic bypass, protein fusion, and intragenic complementation assays define two
distinct additional mechanisms of TPP1 involvement in telomerase action at
telomeres. We demonstrate that TPP1 provides an essential step of telomerase
activation as well as feedback regulation of telomerase by telomere length, which
is necessary to determine the appropriate telomere length set point in human
embryonic stem cells. These studies reveal and resolve multiple TPP1 roles in
telomere elongation and stem cell telomere length homeostasis.
PMID- 25128435
TI - Resolution of genetic map expansion caused by excess heterozygosity in plant
recombinant inbred populations.
AB - Recombinant inbred populations of many plant species exhibit more heterozygosity
than expected under the Mendelian model of segregation. This segregation
distortion causes the overestimation of recombination frequencies and consequent
genetic map expansion. Here we build upon existing genetic models of differential
zygotic viability to model a heterozygote fitness term and calculate expected
genotypic proportions in recombinant inbred populations propagated by selfing. We
implement this model using the existing open-source genetic map construction code
base for R/qtl to estimate recombination fractions. Finally, we show that
accounting for excess heterozygosity in a sorghum recombinant inbred mapping
population shrinks the genetic map by 213 cM (a 13% decrease corresponding to
4.26 fewer recombinations per meiosis). More accurate estimates of linkage
benefit linkage-based analyses used in the identification and utilization of
causal genetic variation.
PMID- 25128436
TI - QTug.sau-3B is a major quantitative trait locus for wheat hexaploidization.
AB - Meiotic nonreduction resulting in unreduced gametes is thought to be the
predominant mechanism underlying allopolyploid formation in plants. Until now,
however, its genetic base was largely unknown. The allohexaploid crop common
wheat (Triticum aestivum L.), which originated from hybrids of T. turgidum L.
with Aegilops tauschii Cosson, provides a model to address this issue. Our
observations of meiosis in pollen mother cells from T. turgidum*Ae. tauschii
hybrids indicated that first division restitution, which exhibited prolonged cell
division during meiosis I, was responsible for unreduced gamete formation. A
major quantitative trait locus (QTL) for this trait, named QTug.sau-3B, was
detected on chromosome 3B in two T. turgidum*Ae. tauschii haploid populations.
This QTL is situated between markers Xgwm285 and Xcfp1012 and covered a genetic
distance of 1 cM in one population. QTug.sau-3B is a haploid-dependent QTL
because it was not detected in doubled haploid populations. Comparative genome
analysis indicated that this QTL was close to Ttam-3B, a collinear homolog of tam
in wheat. Although the relationship between QTug.sau-3B and Ttam requires further
study, high frequencies of unreduced gametes may be related to reduced expression
of Ttam in wheat.
PMID- 25128437
TI - Performance of the Cas9 nickase system in Drosophila melanogaster.
AB - Recent studies of the Cas9/sgRNA system in Drosophila melanogaster genome editing
have opened new opportunities to generate site-specific mutant collections in a
high-throughput manner. However, off-target effects of the system are still a
major concern when analyzing mutant phenotypes. Mutations converting Cas9 to a
DNA nickase have great potential for reducing off-target effects in vitro. Here,
we demonstrated that injection of two plasmids encoding neighboring offset sgRNAs
into transgenic Cas9(D10A) nickase flies efficiently produces heritable indel
mutants. We then determined the effective distance between the two sgRNA targets
and their orientations that affected the ability of the sgRNA pairs to generate
mutations when expressed in the transgenic nickase flies. Interestingly, Cas9
nickase greatly reduces the ability to generate mutants with one sgRNA,
suggesting that the application of Cas9 nickase and sgRNA pairs can almost avoid
off-target effects when generating indel mutants. Finally, a defined piwi mutant
allele is generated with this system through homology-directed repair. However,
Cas9(D10A) is not as effective as Cas9 in replacing the entire coding sequence of
piwi with two sgRNAs.
PMID- 25128432
TI - The construct of the multisensory temporal binding window and its dysregulation
in developmental disabilities.
AB - Behavior, perception and cognition are strongly shaped by the synthesis of
information across the different sensory modalities. Such multisensory
integration often results in performance and perceptual benefits that reflect the
additional information conferred by having cues from multiple senses providing
redundant or complementary information. The spatial and temporal relationships of
these cues provide powerful statistical information about how these cues should
be integrated or "bound" in order to create a unified perceptual representation.
Much recent work has examined the temporal factors that are integral in
multisensory processing, with many focused on the construct of the multisensory
temporal binding window - the epoch of time within which stimuli from different
modalities is likely to be integrated and perceptually bound. Emerging evidence
suggests that this temporal window is altered in a series of neurodevelopmental
disorders, including autism, dyslexia and schizophrenia. In addition to their
role in sensory processing, these deficits in multisensory temporal function may
play an important role in the perceptual and cognitive weaknesses that
characterize these clinical disorders. Within this context, focus on improving
the acuity of multisensory temporal function may have important implications for
the amelioration of the "higher-order" deficits that serve as the defining
features of these disorders.
PMID- 25128439
TI - Uncovering zoonoses awareness in an emerging disease 'hotspot'.
AB - Emerging infectious diseases from animals pose significant and increasing threats
to human health; places of risk are simultaneously viewed as conservation and
emerging disease 'hotspots'. The One World/One Health paradigm is an 'assemblage'
discipline. Extensive research from the natural and social sciences, as well as
public health have contributed to designing surveillance and response policy
within the One World/One Health framework. However, little research has been
undertaken that considers the lives of those who experience risk in hotspots on a
daily basis. As a result, policymakers and practitioners are unable to fully
comprehend the social and ecological processes that catalyze cross-species
pathogen exchange. This study examined local populations' comprehension of
zoonotic disease. From October 2008-May 2009 we collected data from people living
on the periphery of Kibale National Park, in western Uganda. We administered a
survey to 72 individuals and conducted semi-structured, in-depth interviews with
14 individuals. Results from the survey showed respondents had statistically
significant awareness that transmission of diseases from animals was possible
compared to those who did not think such transmission was possible (x(2) = 30.68,
df = 1, p < 0.05). However, individual characteristics such as gender,
occupation, location, and age were not significantly predictive of awareness.
Both quantitative and qualitative data show local people are aware of zoonoses
and provided biomedically accurate examples of possible infections and
corresponding animal sources (e.g., worm infection from pigs and Ebola from
primates). Qualitative data also revealed expectations about the role of the
State in managing the prevention of zoonoses from wildlife. As a result of this
research, we recommend meaningful discourse with people living at the frontlines
of animal contact in emerging disease and conservation hotspots in order to
develop informed and relevant zoonoses prevention practices that take into
account local knowledge and perceptions.
PMID- 25128438
TI - Widespread genomic incompatibilities in Caenorhabditis elegans.
AB - In the Bateson-Dobzhansky-Muller (BDM) model of speciation, incompatibilities
emerge from the deleterious interactions between alleles that are neutral or
advantageous in the original genetic backgrounds, i.e., negative epistatic
effects. Within species such interactions are responsible for outbreeding
depression and F2 (hybrid) breakdown. We sought to identify BDM incompatibilities
in the nematode Caenorhabditis elegans by looking for genomic regions that
disrupt egg laying; a complex, highly regulated, and coordinated phenotype.
Investigation of introgression lines and recombinant inbred lines derived from
the isolates CB4856 and N2 uncovered multiple incompatibility quantitative trait
loci (QTL). These QTL produce a synthetic egg-laying defective phenotype not seen
in CB4856 and N2 nor in other wild isolates. For two of the QTL regions, results
are inconsistent with a model of pairwise interaction between two loci,
suggesting that the incompatibilities are a consequence of complex interactions
between multiple loci. Analysis of additional life history traits indicates that
the QTL regions identified in these screens are associated with effects on other
traits such as lifespan and reproduction, suggesting that the incompatibilities
are likely to be deleterious. Taken together, these results indicate that
numerous BDM incompatibilities that could contribute to reproductive isolation
can be detected and mapped within C. elegans.
PMID- 25128440
TI - Direct costs associated with the management of progressive early onset scoliosis:
estimations based on gold standard technique or with magnetically controlled
growing rods.
AB - BACKGROUND: The main disadvantage of the surgical management of early onset
scoliosis (EOS) using conventional growing rods is the need for iterative
surgical procedures during childhood. The emergence of an innovative device using
distraction-based magnetically controlled growing rods (MCGR) provides the
opportunity to avoid such surgeries and therefore to improve the patient's
quality of life. HYPOTHESIS: Despite the high cost of MCGR and considering its
potential impact in reducing hospital stays, the use of MCGR could reduce medical
resource consumption in a long-term view in comparison to traditional growing rod
(TGR). MATERIALS AND METHODS: A cost-simulation model was constructed to assess
the incremental cost between the two strategies. The cost for each strategy was
estimated based on probability of medical resource consumption determined from
literature search as well as data from EOS patients treated in our centre. Some
medical expenses were also estimated from expert interviews. The time horizon
chosen was 4 years as from first surgical implantation. Costs were calculated in
the perspective of the French sickness fund (using rates from year 2013) and were
discounted by an annual rate of 4%. Sensitivity analyses were conducted to test
model strength to various parameters. RESULTS: With a time horizon of 4 years,
the estimated direct costs of TGR and MCGR strategies were 49,067 ? and 42,752 ?,
respectively leading to an incremental costs of 6135 ? in favour of MCGR
strategy. In the first case, costs were mainly represented by hospital stays
expenses (83.9%) whereas in the other the cost of MCGR contributed to 59.5% of
the total amount. In the univariate sensitivity analysis, the tariffs of hospital
stays, the tariffs of the MCG, and the frequency of distraction surgeries were
the parameters with the most important impact on incremental cost. DISCUSSION:
MCGR is a recent and promising innovation in the management of severe EOS.
Besides improving the quality of life, its use in the treatment of severe EOS is
likely to be offset by lower costs of hospital stays. LEVEL OF EVIDENCE (WITH
STUDY DESIGN): Level IV, economic and decision analyses, retrospective study.
PMID- 25128441
TI - Epidemiology and outcomes in patients with severe sepsis admitted to the hospital
wards.
AB - PURPOSE: The purpose of this study was to detail the trajectory and outcomes of
patients with severe sepsis admitted from the emergency department to a non
intensive care unit (ICU) setting and identify risk factors associated with
adverse outcomes. MATERIAL AND METHODS: This was a single-center retrospective
cohort study conducted at a tertiary, academic hospital in the United States
between 2005 and 2009. The primary outcome was a composite outcome of ICU
transfer within 48 hours of admission and/or 28-day mortality. RESULTS: Of 1853
patients admitted with severe sepsis, 841 (45%) were admitted to a non-ICU
setting, the rate increased over time (P < .001), and 12.5% of these patients
were transferred to the ICU within 48 hours and/or died within 28 days. In
multivariable models, age (P < .001), an oncology diagnosis (P < .001), and
illness severity as measured by Acute Physiologic and Chronic Health Evaluation
II (P = .04) and high (>=4 mmol/L) initial serum lactate levels (P = .005) were
associated with the primary outcome. CONCLUSIONS: Patients presenting to the
emergency department with severe sepsis were frequently admitted to a non-ICU
setting, and the rate increased over time. Of 8 patients admitted to the hospital
ward, one was transferred to the ICU within 48 hours and/or died within 28 days
of admission. Factors present at admission were identified that were associated
with adverse outcomes.
PMID- 25128443
TI - Prostate pointers and pitfalls: the 10 most prevalent problems in prostate biopsy
interpretation.
AB - As small volumes of prostate cancer are being detected with ever-increasing
frequency, the pathologist is challenged to make more diagnostically out of less.
This photoessay explores ten diagnostic problems that are noted with regularity
by a provider of second opinions in prostate biopsy interpretation. These
include: suboptimal submission of prostate cores, atypia with small size of the
focus of concern, cytologic ambiguity of the focus of concern, issues with
ordering and interpreting immunostains, atypia arising with high-grade prostatic
intraepithelial neoplasia, benign mimics of cancer, omitting mention of
extraprostatic tumor extension or of Gleason pattern 5, not recognizing
intraductal carcinoma, and the differential diagnosis of cancer of urothelial
versus prostatic origin.
PMID- 25128442
TI - Mitochondrial DNA neutrophil extracellular traps are formed after trauma and
subsequent surgery.
AB - INTRODUCTION: Neutrophil extracellular traps (NETs) have not been demonstrated
after trauma and subsequent surgery. Neutrophil extracellular traps are formed
from pure mitochondrial DNA (mtDNA) under certain conditions, which is potently
proinflammatory. We hypothesized that injury and orthopedic trauma surgery would
induce NET production with mtDNA as a structural component. METHODS: Neutrophils
were isolated 8 trauma patients requiring orthopedic surgery postinjury and up to
5 days postoperatively. Four healthy volunteers provided positive and negative
controls. Total hip replacement patients acted as an uninjured surgical control
group. Neutrophil extracellular traps were visualized with DNA (Hoechst
33342TM/Sytox Green/MitoSox/MitoTracker) stains using live cell fluorescence
microscopy with downstream quantitative polymerase chain reaction analysis of DNA
composition. RESULTS: Neutrophil extracellular traps were present after injury in
all 8 trauma patients. They persisted for 5 days postoperatively. Delayed surgery
resulted in NET resolution, but they reformed postoperatively. Total hip
replacement patients developed NETs postoperatively, which resolved by day 5.
Quantitative polymerase chain reaction analysis of NET-DNA composition revealed
that NETs formed after injury and surgery were made of mtDNA with no detectable
nuclear DNA component. CONCLUSIONS: Neutrophil extracellular traps formed after
major trauma and subsequent surgery contain mtDNA and represent a novel marker of
heightened innate immune activation. They could be considered when timing surgery
after trauma to prevent systemic NET-induced inflammatory complications.
PMID- 25128445
TI - Endogenous allergens in the regulatory assessment of genetically engineered
crops.
AB - A scientific approach to the assessment of foods derived from genetically
engineered (GE) crops is critical to maintaining objectivity and public
confidence in regulatory decisions. Principles developed at the international
level support regulators and enable robust and transparent safety assessments. A
comparison of key constituents in the GE crop with a suitable comparator is an
important element of an assessment. In Europe, endogenous allergens would be
included in the comparative analysis, however this approach has been hindered by
technical limitations on the ability to accurately measure identified allergenic
proteins. Over recent years, improved proteomic methods have enabled researchers
to focus on major allergenic proteins in conventional food crops, as information
on natural variability is largely lacking. Emerging data for soybean indicate
that variability in levels of major allergens already in the food supply is
broad. This raises questions about the biological interpretation of differences
between a GE plant and its conventional counterpart, in particular, whether any
conclusions about altered allergenicity could be inferred. This paper discusses
the scientific justification for requiring proteomic analysis of endogenous
allergens as part of the evaluation. Ongoing scientific review and corresponding
international discussion are integral to ensuring that data requirements address
legitimate risk assessment questions.
PMID- 25128444
TI - Impact of prolapse meshes on the metabolism of vaginal extracellular matrix in
rhesus macaque.
AB - OBJECTIVE: The impact of polypropylene mesh implantation on vaginal collagen and
elastin metabolism was analyzed using a nonhuman primate model to further
delineate the mechanism of mesh induced complications. STUDY DESIGN: Forty-nine
middle-aged parous rhesus macaques underwent surgical implantation of 3 synthetic
meshes via sacrocolpopexy. Gynemesh PS (n = 12) (Ethicon, Somerville, NJ) and 2
lower-weight, higher-porosity, lower-stiffness meshes (UltraPro [n = 19]
[Ethicon] and Restorelle [n = 8] [Coloplast, Minneapolis, MN]) were implanted, in
which UltraPro was implanted with its blue orientation lines perpendicular (low
stiffness direction, n = 11) and parallel (high stiffness direction, n = 8) to
the longitudinal axis of the vagina. Sham-operated animals were used as controls
(n = 10). Twelve weeks after surgery, the mesh-tissue complex was excised and
analyzed. RESULTS: Relative to sham, Gynemesh PS had a negative impact on the
metabolism of both collagen and elastin-favoring catabolic reactions, whereas
UltraPro induced an increase only in elastin degradation. Restorelle had the
least impact. As compared with sham, the degradation of collagen and elastin in
the vagina implanted with Gynemesh PS was increased with a simultaneous increase
in active matrix metalloproteinase (MMP)-1, -8, -13, and total MMP-2 and -9 (all
P < .05). The degradation of elastin (tropoelastin and mature elastin) was
increased in the UltraPro-implanted vagina with a concomitant increase of MMP-2,
and -9 (all P < .05). Collagen subtype ratio III/I was increased in Gynemesh PS
and UltraPro perpendicular groups (P < .05). CONCLUSION: Following implantation
with the heavier, less porous, and stiffer mesh, Gynemesh PS, the degradation of
vaginal collagen and elastin exceeded synthesis, most likely as a result of
increased activity of MMPs, resulting in a structurally compromised tissue.
PMID- 25128446
TI - Pediatric cochlear implant revision surgery and reimplantation: an analysis of
957 cases.
AB - OBJECTIVE: In this study causes, risk factors, prevention strategies,
diffuculties encountered during revision cochlear implant surgery, reimplantation
in pediatric age group were evaluated. METHODS: Charts of 957 CI patients younger
than 18 years of age implanted at Izmir Bozyaka Teaching and Research Hospital
between 1998 and July 2012 and 18 referred CI complications at same age group
were retrospectively evaluated. Revision and reimplantation surgeries were
systematically reviewed. RESULTS: We encountered 26 surgical complications in 24
patients and 36 device related problems in 36 patients. Eighteen referred cases
including 7 surgical complications and 11 device related problems were also
evaluated. A total number of 80 complications were evaluated. In 11 cases
conservative management was successful, 19 revision surgery was performed but we
failed in 4 cases. We reimplanted 48 cases and 4 additional cases were implanted
after failed revision surgery. Implant was extracted in one case. In one case we
could implant the other side. Forty-six of reimplantations were done in one stage
surgery, 5 cases required second stage surgery. CONCLUSIONS: Surgical
complications and device related problems of cochlear implantation may be
different in children and majority of them require revision surgery or
reimplantation. Although surgical problems leading to revision surgery and
reimplantation are expected to diminish by experience every center has to deal
with device failures. Both revision surgery and reimplantation require extra care
and it should be better carried out by experienced surgeons. Implant performances
are expected to be comparable with primary implantations.
PMID- 25128447
TI - Aided cortical response, speech intelligibility, consonant perception and
functional performance of young children using conventional amplification or
nonlinear frequency compression.
AB - OBJECTIVE: The aim of this study was to compare conventional processing with
nonlinear frequency compression (NLFC) in hearing aids for young children with
bilateral hearing loss. METHODS: Sixty-four children aged between 2 and 7 years
with bilateral hearing aids were recruited. Evaluations of cortical responses,
speech intelligibility rating, consonant perception and functional performance
were completed with the children wearing their personal hearing aids with
conventional processing. The children were then refitted with new hearing aids
with NLFC processing. Following a six-week familiarization period, they were
evaluated again while using their hearing aids with NLFC activated. RESULTS: The
mean speech intelligibility rating and the number of cortical responses present
for /s/were significantly higher when children were using NLFC processing than
conventional processing in their hearing aids (p<0.05). Parents judged the
children's functional real life performance with the NLFC hearing aids to be
similar or better than that with the children's own hearing aids in both quiet
and noisy situations. The mean percent consonant score was higher with NLFC
processing compared to conventional processing, but the difference did not reach
the 5% significance level (p=0.056). An overall figure of merit (FOM) was
calculated by averaging the standardized difference scores between processing
schemes for all measures. Regression analysis revealed that, on average, greater
advantage for NLFC processing was associated with poorer hearing at 4 kHz.
CONCLUSIONS: Compared to conventional processing, the use of NLFC was, on
average, effective in increasing audibility of /s/as measured by cortical
evaluations, and higher ratings on speech intelligibility and functional
performance in real life by parents. On average, greater benefits from NLFC
processing was associated with poorer hearing at 4 kHz.
PMID- 25128448
TI - Respiratory viruses are continuously detected in children with chronic
tonsillitis throughout the year.
AB - OBJECTIVE: To evaluate the oscillations on the viral detection in adenotonsillar
tissues from patients with chronic adenotonsillar diseases as an indicia of the
presence of persistent viral infections or acute subclinical infections. STUDY
DESIGN: Cross-sectional prospective study. SETTING: Tertiary hospital. METHODS:
The fluctuations of respiratory virus detection were compared to the major
climatic variables during a two-year period using adenoids and palatine tonsils
from 172 children with adenotonsillar hypertrophy and clinical evidence of
obstructive sleep apnoea syndrome or recurrent adenotonsillitis, without symptoms
of acute respiratory infection (ARI), by TaqMan real-time PCR. RESULTS: The rate
of detection of at least one respiratory virus in adenotonsillar tissue was 87%.
The most frequently detected viruses were human adenovirus in 52.8%, human
enterovirus in 47.2%, human rhinovirus in 33.8%, human bocavirus in 31.1%, human
metapneumovirus in 18.3% and human respiratory syncytial virus in 17.2%. Although
increased detection of human enterovirus occurred in summer/autumn months, and
there were summer nadirs of human respiratory syncytial virus in both years of
the study, there was no obvious viral seasonality in contrast to reports with ARI
patients in many regions of the world. CONCLUSION: Respiratory viruses are
continuously highly detected during whole year, and without any clinical
symptomatology, indicating that viral genome of some virus can persist in
lymphoepithelial tissues of the upper respiratory tract.
PMID- 25128449
TI - Prevalence and types of articulation errors in Saudi Arabic-speaking children
with repaired cleft lip and palate.
AB - OBJECTIVES: The purpose of this study was to assess prevalence and types of
consonant production errors and phonological processes in Saudi Arabic-speaking
children with repaired cleft lip and palate, and to determine the relationship
between frequency of errors on one hand and the type of the cleft. Possible
relationship between age, gender and frequency of errors was also investigated.
METHODS: Eighty Saudi children with repaired cleft lip and palate aged 6-15 years
(mean 6.7 years), underwent speech, language, and hearing evaluation. The
diagnosis of articulation deficits was based on the results of an Arabic
articulation test. Phonological processes were reported based on the productivity
scale of a minimum 20% of occurrence. Diagnosis of nasality was based on a 5
point scale that reflects severity from 0 through 4. All participants underwent
intraoral examination, informal language assessment, and hearing evaluation to
assess their speech and language abilities. The Chi-Square test for independence
was used to analyze the results of consonant production as a function of type of
CLP and age. RESULTS: Out of 80 participants with CLP, 21 participants had normal
articulation and resonance, 59 of participants (74%) showed speech abnormalities.
Twenty-one of these 59 participants showed only articulation errors; 17 showed
only hypernasality; and 21 showed both articulation and resonance deficits. CAs
were observed in 20 participant. The productive phonological processes were
consonant backing, final consonant deletion, gliding, and stopping. At age 6 and
older, 37% of participants had persisting hearing loss. CONCLUSIONS: Despite
early age at time of surgery (mean 6.7 months) for the studied CLP participants
in this study, a substantial number of them demonstrated articulation errors and
hypernasality. The results showed desirable findings for diverse languages. It is
especially interesting to consider the prevalence of glottal stops and pharyngeal
fricatives in a population for whom these sound are phonemic.
PMID- 25128450
TI - Acetaminophen plus ibuprofen versus opioids for treatment of post-tonsillectomy
pain in children.
AB - OBJECTIVE: To determine the efficacy and safety of acetaminophen plus ibuprofen
in treatment of post-tonsillectomy pain compared to acetaminophen plus opioids in
children. STUDY DESIGN: Retrospective medical record review. SETTING: Tertiary
care children's hospital between September 2012 and March 2013. SUBJECTS AND
METHODS: All children undergoing total tonsillectomy (n=1065). Analysis included
descriptive analysis, chi-square testing, and logistic regression controlling for
age, diagnosis, trainee involvement, concurrent surgical procedures, and Coblator
use for differences of outcomes: (1) post-operative bleeding, (2) emergency
department (ED) visits for pain, dehydration, or bleeding, and (3) nurse phone
calls from families. RESULTS: All patients received acetaminophen. Seventy-four
percent received ibuprofen (n=783) and 26.5% did not receive ibuprofen (n=282).
In the ibuprofen group, 32.2% received opioids (n=252). Over eight percent of
children had post-operative hemorrhage of any amount reported (n=89). Forty-eight
percent of these required operative intervention (n=43). Ibuprofen prescription
did not impact post-operative bleeding; operative intervention for bleeding, ED
visits, or nurse phone calls either on chi-squared or logistic regression
testing. Increasing age was found to increase bleeding risk as well as the
likelihood of visiting the ED or calling the clinic nurses. All patients with
multiple bleeding episodes were in the ibuprofen group. CONCLUSION: Prescription
of ibuprofen did not increase the risk of bleeding and did not increase the
likelihood of a post-operative ED visit or nurse phone call. Ibuprofen
prescription may possibly increase the risk of multiple bleeding episodes, but
further prospective studies are needed. Increased age increases the risk of
bleeding, ED visits, and nurse phone calls.
PMID- 25128451
TI - Specificity of coliphages in evaluating marker efficacy: a new insight for water
quality indicators.
AB - Conventional procedures for qualitative assessment of coliphage are time
consuming multiple step approach for achieving results. A modified and rapid
technique has been introduced for determination of coliphage contamination among
potable water sources during water borne outbreaks. During December 2013, 40
water samples from different potable water sources, were received for water
quality analyses, from a jaundice affected Municipality of West Bengal, India.
Altogether, 30% water samples were contaminated with coliform (1-20 cfu/ml) and
5% with E. coli (2-5 cfu/ml). Among post-outbreak samples, preponderance of
coliform has decreased (1-4 cfu/ml) with total absence of E. coli. While standard
technique has detected 55% outbreak samples with coliphage contamination,
modified technique revealed that 80%, double than that of bacteriological
identification rate, were contaminated with coliphages (4-20 pfu/10 ml). However,
post-outbreak samples were detected with 1-5 pfu/10 ml coliphages among 20%
samples. Coliphage detection rate through modified technique was nearly double
(50%) than that of standard technique (27.5%). In few samples (with coliform load
of 10-100 cfu/ml), while modified technique could detect coliphages among six
samples (10-20 pfu/10 ml), standard protocol failed to detect coliphage in any of
them. An easy, rapid and accurate modified technique has thereby been implemented
for coliphage assessment from water samples. Coliform free water does not always
signify pathogen free potable water and it is demonstrated that coliphage is a
more reliable 'biomarker' to ascertain contamination level in potable water.
PMID- 25128452
TI - Wetting of nanophases: Nanobubbles, nanodroplets and micropancakes on hydrophobic
surfaces.
AB - The observation by Atomic Force Microscopy of a range of nanophases on
hydrophobic surfaces poses some challenging questions, not only related to the
stability of these objects but also regarding their wetting properties. Spherical
capped nanobubbles are observed to exhibit contact angles that far exceed the
macroscopic contact angle measured for the same materials, whereas nanodroplets
exhibit contact angles that are much the same as the macroscopic contact angle.
Micropancakes are reported to consist of gas, in which case their wetting
properties are mysterious. They should only be stable when the van der Waals
forces act to thicken the film whereas for a gas, the van der Waals forces will
always act to thin the film. Here we examine the available evidence and
contribute some additional experiments in order to review our understanding of
the wetting properties of these nanophases. We demonstrate that if in fact
micropancakes consist of a contaminant their wetting properties can be explained,
though the very high contact angles of nanobubbles remain unexplained.
PMID- 25128453
TI - Serum levels of BDNF, folate and homocysteine: in relation to hippocampal volume
and psychopathology in drug naive, first episode schizophrenia.
AB - OBJECTIVE: The present study was to examine serum levels of brain-derived
neurotrophic factor (BDNF), folate, homocysteine (Hcy), and their relationships
with hippocampal volume and psychopathology in drug naive, first episode
schizophrenia. METHOD: Drug naive, first episode schizophrenia patients and
healthy controls were enrolled in the study. Serum levels of BDNF, folate and Hcy
were measured using enzyme-linked immunosorbent assay (ELISA),
electrochemiluminescence immunoassay (ECLIA), and enzymatic cycling method
respectively. Hippocampus was parcellated and bilateral hippocampal volumes were
measured using FreeSurfer. RESULTS: Forty-six patients with drug naive, first
episode schizophrenia (SZ group) and 30 healthy controls (control group) were
enrolled. The SZ group had significantly lower serum levels of BDNF and folate,
and significantly higher serum levels of Hcy compared with the control group
(p=0.013, p<0.001, p=0.003 respectively). There were no significant differences
in hippocampal volumes between the two groups (ps>0.2). Within the SZ group,
there were significant positive relationships between serum levels of BDNF and
both left and right hippocampal volumes (r=0.327, p=0.026; r=0.338, p=0.022
respectively). In contrast, such relationships did not exist in the control
group. Within the SZ group, there were significant negative relationships between
serum levels of folate and PANSS-total scores and PANSS-negative symptom scores
(r=0.319, p=0.031; r=0.321, p=0.030 respectively); and there was a positive
relationship between serum levels of Hcy and PANSS-total scores (r=0.312,
p=0.035). Controlling for potential confounding variables resulted in similar
findings. CONCLUSIONS: Drug naive, first episode schizophrenia presents decreased
serum levels of BDNF, folate and increased serum levels of Hcy, which may play an
important role in the neurodevelopmental process and clinical manifestation of
schizophrenia.
PMID- 25128454
TI - Standard cardiovascular disease risk algorithms underestimate the risk of
cardiovascular disease in schizophrenia: evidence from a national primary care
database.
AB - BACKGROUND: Schizophrenia is associated with increased cardiovascular mortality.
Although cardiovascular disease (CVD) risk prediction algorithms are widely in
the general population, their utility for patients with schizophrenia is unknown.
METHODS: A primary care dataset was used to compare CVD risk scores (Joint
British Societies (JBS) score), cardiovascular risk factors, rates of pre
existing CVD and age of first diagnosis of CVD for schizophrenia (n=1997)
relative to population controls (n=215,165). RESULTS: Pre-existing rates of CVD
and the recording of risk factors for those without CVD were higher in the
schizophrenia cohort in the younger age groups, for both genders. Those with
schizophrenia were more likely to have a first diagnosis of CVD at a younger age,
with nearly half of men with schizophrenia plus CVD diagnosed under the age of 55
(schizophrenia men 46.1% vs. control men 34.8%, p<0.001; schizophrenia women
28.9% vs. control women 23.8%, p<0.001). However, despite high rates of CVD risk
factors within the schizophrenia group, only a very small percentage (3.2% of men
and 7.5% of women) of those with schizophrenia under age 55 were correctly
identified as high risk for CVD according to the JBS risk algorithm. CONCLUSION:
The JBS2 risk score identified only a small proportion of individuals with
schizophrenia under the age of 55 as being at high risk of CVD, despite high
rates of risk factors and high rates of first diagnosis of CVD within this age
group. The validity of CVD risk prediction algorithms for schizophrenia needs
further research.
PMID- 25128456
TI - Discovery of a novel HIV-1 integrase inhibitor from natural compounds through
structure based virtual screening and cell imaging.
AB - The interaction between HIV-1 integrase and LEDGF/P75 has been validated as a
target for anti-HIV drug development. Based on the crystal structure of integrase
in complex with LEDGF/P75, a library containing 80 thousand natural compounds was
filtered with virtual screening. 11 hits were selected for cell based assays. One
compound, 3-(1,3-benzothiazol-2-yl)-8-{[bis(2-hydroxyethyl)amino]methyl}-7
hydroxy-2H-chromen-2-one (D719) inhibited integrase nuclear translocation in cell
imaging. The binding mode of D719 was analyzed with molecular simulation. The
anti-HIV activity of D719 was assayed by measuring the p24 antigen production in
acute infection. The structure characteristics of D719 may provide valuable
information for integrase inhibitor design.
PMID- 25128455
TI - Poly (ADP-ribose) polymerase inhibition enhances trastuzumab antitumour activity
in HER2 overexpressing breast cancer.
AB - AIM: Poly (ADP-ribose) polymerase (PARP) inhibitors have shown promising results
in Breast Cancer (BRCA) deficient breast cancer, but not in molecularly
unselected patient populations. Two lines of research in this field are needed:
the identification of novel subsets of patients that could potentially benefit
from PARP inhibitors and the discovery of suitable targeted therapies for
combination strategies. METHODS: We tested PARP inhibition, alone or combined
with the anti-HER2 antibody trastuzumab on HER2+ breast cancer. We used two PARP
inhibitors in clinical development, olaparib and rucaparib, as well as genetic
downmodulation of PARP-1 for in vitro studies. DNA damage was studied by the
formation of gammaH2AX foci and comet assay. Finally, the in vivo anti-tumour
effect of olaparib and trastuzumab was examined in nude mice subcutaneously
implanted with BT474 cells. RESULTS: In a panel of four HER2 overexpressing
breast cancer cell lines, both olaparib and rucaparib significantly decreased
cell growth and enhanced anti-tumour effects of trastuzumab. Cells exposed to
olaparib and trastuzumab had greater DNA damage than cells exposed to each agent
alone. Mechanistic exploratory assays showed that trastuzumab downmodulated the
homologous recombination protein proliferating cell nuclear antigen (PCNA).
Combination treatment in the BT474 xenograft model resulted in enhanced growth
inhibition, reduced tumour cell proliferation, and increased DNA damage and
apoptosis. CONCLUSION: Taken together, our results show that PARP inhibition has
antitumour effects and increases trastuzumab activity in HER2 overexpressing
breast cancer. These findings make this novel combination a promising strategy
for clinical development.
PMID- 25128457
TI - Red chlorophyll excitation dynamics in Arthrospira platensis photosystem I
trimeric complexes as studied by femtosecond transient absorption spectroscopy.
AB - Femtosecond absorption spectroscopy was applied to study for the first time
excitation dynamics in isolated photosystem I trimers from Arthrospira platensis,
which display extremely long-wavelength absorption peaks. Pump-probe spectra
observed at 77K in the timescale of dozens of picoseconds upon 70-fs excitation
revealed two maxima near 710 and 730 nm, which correspond to red chlorophyll
forms. Bleaching at 680 nm developed in ~ 200 fs, whereas the bleaching kinetics
at 710 and 730 nm exhibited two components with time constants of 1 and 5.5 ps.
Comparison of the kinetics of bleaching development at 710 nm and 730 nm with
that of bleaching decay at 680 nm indicated that both long-wavelength forms of
trimers are populated mainly via direct energy transfer from bulk chlorophyll.
PMID- 25128458
TI - mTOR regulates the nucleoplasmic diffusion of Xrn2 under conditions of heat
stress.
AB - Stress induces various responses, including translational suppression and tRNA
degradation in mammals. Previously, we showed that heat stress induces
degradation of initiator tRNA(Met) (iMet) through 5'-3' exoribonuclease Xrn1 and
Xrn2, respectively. In addition, we found that rapamycin inhibits the degradation
of iMet under heat stress conditions. Here, we report that the mammalian target
of rapamycin (mTOR) regulates the diffusion of Xrn2 from the nucleolus to the
nucleoplasm, facilitating the degradation of iMet under conditions of heat
stress. Our results suggest a mechanism of translational suppression through mTOR
regulated iMet degradation in mammalian cells.
PMID- 25128459
TI - MicroRNAs in the interaction between host and bacterial pathogens.
AB - MicroRNAs (miRNAs) are small non-coding RNAs with a central role in the post
transcriptional control of gene expression, that have been implicated in a wide
range of biological processes. Regulation of miRNA expression is increasingly
recognized as a crucial part of the host response to infection by bacterial
pathogens, as well as a novel molecular strategy exploited by bacteria to
manipulate host cell pathways. Here, we review the current knowledge of bacterial
pathogens that modulate host miRNA expression, focusing on mammalian host cells,
and the implications of miRNA regulation on the outcome of infection. The
emerging role of commensal bacteria, as part of the gut microbiota, on host miRNA
expression in the presence or absence of bacterial pathogens is also discussed.
PMID- 25128460
TI - Vitamin D reduces the differentiation and expansion of Th17 cells in young
asthmatic children.
AB - Vitamin D [25(OH)D3] deficiency has been associated with asthma as in many
inflammatory and autoimmune pathologies; however, there is still a lack of data
about the effects of administration of vitamin D in immune regulation in young
asthmatic patients. In this study, we investigated its inhibitory effect on the
immune response in young asthmatic patients and the possible mechanisms involved.
Peripheral blood CD4(+) T cells from 10 asthmatic patients and 10 healthy
controls were cultured under Th17 polarizing conditions in the presence or
absence of [25(OH)D3], IL-17 cytokine production was determined by ELISA and flow
cytometry. Messenger RNA (mRNA) expression of several factors related to Th17
cell function was determined by real-time PCR. The effect of [25(OH)D3]-treated
dendritic cells (DCs) on CD4(+) T cell response was determined by ELISA and flow
cytometry. Stimulation of naive CD4(+) T cells under Th17 polarizing conditions
showed a higher Th17 cell differentiation in asthmatic patients than healthy
controls. The addition of [25(OH)D3] significantly inhibited Th17 cell
differentiation both in patients [P<0.001] and in normal controls [P=0.001] in a
dose-dependent way. [25(OH)D3] was able to inhibit the gene expression of RORC,
IL-17, IL-23R, and CCR6. [25(OH)D3]-treated DCs significantly inhibited IL-17
production [P=0.002] and decreased the percentage of CD4(+)IL-17(+) [P=0.007] in
young asthmatics. The findings suggest that the inhibitory effect of [25(OH)D3]
on the Th17 response was mediated via both T cells and DCs. DCs pathway is
involved in the direct inhibition of 25(OH)D3 on Th17 cell differentiation in
young asthmatics.
PMID- 25128461
TI - Measures of outdoor play and independent mobility in children and youth: A
methodological review.
AB - OBJECTIVES: Declines in children's outdoor play have been documented globally,
which are partly due to heightened restrictions around children's independent
mobility. Literature on outdoor play and children's independent mobility is
increasing, yet no paper has summarized the various methodological approaches
used. A methodological review could highlight most commonly used measures and
comprehensive research designs that could result in more standardized
methodological approaches. DESIGN: Methodological review. METHODS: A standardized
protocol guided a methodological review of published research on measures of
outdoor play and children's independent mobility in children and youth (0-18
years). Online searches of 8 electronic databases were conducted and studies
included if they contained a subjective/objective measure of outdoor play or
children's independent mobility. References of included articles were scanned to
identify additional articles. RESULTS: Twenty-four studies were included on
outdoor play, and twenty-three on children's independent mobility. Study designs
were diverse. Common objective measures included accelerometry, global
positioning systems and direct observation; questionnaires, surveys and
interviews were common subjective measures. Focus groups, activity logs,
monitoring sheets, travel/activity diaries, behavioral maps and guided tours were
also utilized. Questionnaires were used most frequently, yet few studies used the
same questionnaire. Five studies employed comprehensive, mixed-methods designs.
CONCLUSIONS: Outdoor play and children's independent mobility have been measured
using a wide variety of techniques, with only a few studies using similar
methodologies. A standardized methodological approach does not exist. Future
researchers should consider including both objective measures (accelerometry and
global positioning systems) and subjective measures (questionnaires, activity
logs, interviews), as more comprehensive designs will enhance understanding of
each multidimensional construct. Creating a standardized methodological approach
would improve study comparisons.
PMID- 25128462
TI - [Incidence, management and costs of adverse effects in chronic hepatitis C
patients on triple therapy with telaprevir or boceprevir: first 12 weeks of
treatment].
AB - INTRODUCTION: The aim of the study was to analyze the incidence, management and
cost associated to hematological and dermatological adverse effects (AE) in
chronic hepatitis C patients on triple therapy (TT) with telaprevir (TVR) or
boceprevir (BOC). METHODS: An analysis was made on the data recorded on patients
who started treatment with TVR or BOC associated with peginterferon alfa and
ribavirin in a 12-week follow-up period. RESULTS: Fifty-three patients were
included (TVR n=36; BOC n=17). Thrombocytopenia (83% TVR vs. 88% BOC) followed by
neutropenia (89% TVR vs. 82% BOC) were the most common AE. Dermatological AE were
observed in 32% of patients. Eleven patients required treatment discontinuation
(all of them received TVR), and toxicity was the main reason for discontinuation
(64%). The percentage of patients who required supportive treatment for
management of AE was 66%. The most used supportive treatment was erythropoietin.
Eight patients required emergency health care, and 2 were hospitalized due to AE.
Total cost of additional supportive resources was 32,522? (625 [SD=876]?/patient)
(TVR 759 [SD=1,022]?/patient vs. BOC 349 [SD=327]?/patient; P>.05). Patients with
gradeiii-iv toxicity required greater supportive care with higher costs, compared
to patients with gradei-ii toxicity (849 [SD=1,143]?/patient vs. 387
[SD=397]?/patient; P=.053). CONCLUSION: The addition of new protease inhibitors
to conventional treatment leads to a higher incidence of hematological AE in our
study, compared to data described in clinical trials. The elevated incidence of
AE involves the use of supportive care, increasing total costs of therapy.
PMID- 25128463
TI - Cocaine- and amphetamine-regulated transcript peptide increases mitochondrial
respiratory chain complex II activity and protects against oxygen-glucose
deprivation in neurons.
AB - The mechanisms of ischemic stroke, a main cause of disability and death, are
complicated. Ischemic stroke results from the interaction of various factors
including oxidative stress, a key pathological mechanism that plays an important
role during the acute stage of ischemic brain injury. This study demonstrated
that cocaine- and amphetamine-regulated transcript (CART) peptide, specifically
CART55-102, increased the survival rate, but decreased the mortality of neurons
exposed to oxygen-glucose deprivation (OGD), in a dose-dependent manner. The
above-mentioned effects of CART55-102 were most significant at 0.4nM. These
results indicated that CART55-102 suppressed neurotoxicity and enhanced neuronal
survival after oxygen-glucose deprivation. CART55-102 (0.4nM) significantly
diminished reactive oxygen species levels and markedly increased the activity of
mitochondrial respiratory chain complex II in oxygen-glucose deprived neurons. In
summary, CART55-102 suppressed oxidative stress in oxygen-glucose deprived
neurons, possibly through elevating the activity of mitochondrial respiratory
chain complex II. This result provides evidence for the development of CART55-102
as an antioxidant drug.
PMID- 25128465
TI - Function of duck RIG-I in induction of antiviral response against IBDV and avian
influenza virus on chicken cells.
AB - The avian influenza (AI) H9N2 virus and IBDV are two major problems in the
poultry industry. They have been prevalent among domestic poultry in Asia for
many years and have caused considerable economic losses. Retinoic-acid-induced
gene I (RIG-I) is a cytoplasmic sensor of dsRNA and ssRNA. It can detect
Encephalomyocarditis virus (EMCV) and vesicular stomatitis virus (VSV) in human
cells, influenza virus in duck leads to production of IFN-beta and IFN-stimulated
antiviral genes and reductions in the replication of RNA virus. Chickens, which
lack RIG-I, are more sensitive to influenza virus than ducks. However, little is
known about the roles of duck RIG-I (dRIG-I) in the detection of IBDV and AI H9N2
in chicken cells DF-1. The purpose of this study was to examine the function of
dRIG-I in the recognition of IBDV Ts strain and H9N2
A/Chicken/Shandong/ZB/2007(ZB07) and in the induction of antiviral gene
expression to gain an understanding of antiviral ability of dRIG-I in chicken
cells against dsRNA virus IBDV and ssRNA virus ZB07. After challenge with the
IBDV Ts strain and ZB07 the expression levels of Type I IFN (IFN-beta and IFN
alpha) and IFN-induced antiviral genes (Mx and PKR) were significantly up
regulated in dRIG-I-transfected DF-1cells compared with the empty-vector
transfected control. dRIG-I knockdown experiments further proved that dRIG-I is
essential to sensing IBDV and ZB07 in duck embryo fibroblasts (DEF). Growth
curves showed that dRIG-I repressed the replication of IBDV and almost blunted
the growth of ZB07 in DF-1. Apoptosis analysis revealed that dRIG-I increase the
number of the survival cells after IBDV Ts strain or ZB07 infection relative to
the empty-vector-transfected control. These results indicate that dRIG-I can up
regulates type I IFN and reduce viral gene expression and viral replication and
protect chicken cells from virus-induced apoptosis during ZB07 and IBDV
infection.
PMID- 25128466
TI - Egress of budded virions of Autographa californica nucleopolyhedrovirus does not
require activity of Spodoptera frugiperda HSP/HSC70 chaperones.
AB - The induction of heat shock proteins in baculovirus infected cells is well
documented. However a role of these chaperones in infection cycle remains
unknown. The observation that HSP70s are associated with virions of different
baculoviruses reported by several researchers suggests that HSPs might be
structural components of viruses or involved in virion assembly. These hypotheses
were examined by using a novel inhibitor of the ATPase and chaperoning activity
of HSP/HSC70s, VER-155008. When VER-155008 was added early in infection, the
synthesis of viral proteins, genome replication and the production of budded
virions (BV) were markedly inhibited indicating the dependence of virus
reproduction on host chaperones. However, BV production was unaffected when VER
155008 was added in the mid-replication phase which is after accumulation of
products required for completion of the viral DNA replication. These results
suggest that the final stages in assembly of BV and their egress from cells do
not depend on chaperone activity of host HSP/HSC70s.
PMID- 25128464
TI - Functional connectivity of dorsal and ventral frontoparietal seed regions during
auditory orienting.
AB - Our ability to refocus auditory attention is vital for even the most routine day
to-day activities. Shifts in auditory attention can be initiated "voluntarily,"
or triggered "involuntarily" by unexpected novel sound events. Here we employed
psychophysiological interaction (PPI) analyses of auditory functional MRI data,
to compare functional connectivity patterns of distinct frontoparietal cortex
regions during cued voluntary vs. novelty-driven involuntary auditory attention
shifting. Overall, our frontoparietal seed regions exhibited significant PPI
increases with auditory cortex (AC) areas during both cued and novelty-driven
orienting. However, significant positive PPI patterns associated with voluntary
auditory attention (cue>novel task regressor), but mostly absent in analyses
emphasizing involuntary orienting (novel>cue task regressor), were observed with
seeds within the frontal eye fields (FEF), superior parietal lobule (SPL), and
right supramarginal gyri (SMG). In contrast, significant positive PPIs associated
selectively with involuntary orienting were observed between ACs and seeds within
the bilateral anterior interior frontal gyri (IFG), left posterior IFG, SMG, and
posterior cingulate cortices (PCC). We also found indices of lateralization of
different attention networks: PPI increases selective to voluntary attention
occurred primarily within right-hemispheric regions, whereas those related to
involuntary orienting were more frequent with left-hemisphere seeds. In
conclusion, despite certain similarities in PPI patterns across conditions, the
more dorsal aspects of right frontoparietal cortex demonstrated wider
connectivity during cued/voluntary attention shifting, whereas certain left
ventral frontoparietal seeds were more widely connected during novelty
triggered/involuntary orienting. Our findings provide partial support for
distinct attention networks for voluntary and involuntary auditory attention.
PMID- 25128467
TI - FoxO proteins' nuclear retention and BH3-only protein Bim induction evoke
mitochondrial dysfunction-mediated apoptosis in berberine-treated HepG2 cells.
AB - Mammalian forkhead-box family members belonging to the 'O' category (FoxO)
manipulate a plethora of genes modulating a wide array of cellular functions
including cell cycle regulation, apoptosis, DNA damage repair, and energy
metabolism. FoxO overexpression and nuclear accumulation have been reported to
show correlation with hindered tumor growth in vitro and size in vivo, while
FoxO's downregulation via phosphatidylinositol 3-kinase (PI3K)/protein kinase B
(Akt) pathway has been linked with tumor promotion. In this study, we have
explored for the first time intervention of berberine, a plant-derived
isoquinoline alkaloid, with FoxO family proteins in hepatoma cells. We observed
that berberine significantly upregulated the mRNA expression of both FoxO1 and
FoxO3a. Their phosphorylation-mediated cytoplasmic sequestration followed by
degradation was prevented by berberine-induced downmodulation of the
PI3K/Akt/mTOR pathway which promoted FoxO nuclear retention. PTEN, a tumor
suppressor gene and negative regulator of the PI3K/Akt axis, was upregulated
while phosphorylation of its Ser380 residue (possible mechanism of PTEN
degradation) was significantly decreased in treated HepG2 cells. Exposure to
berberine induced a significant increase in transcriptional activity of FoxO, as
shown by GFP reporter assay. FoxO transcription factors effectively heightened
BH3-only protein Bim expression, which in turn, being a direct activator of
proapoptotic protein Bax, altered Bax/Bcl-2 ratio, culminating into mitochondrial
dysfunction, caspases activation, and DNA fragmentation. The pivotal role of Bim
in berberine-mediated cytotoxicity was further corroborated by knockdown
experiments where Bim-silencing partially restored HepG2 cell viability during
berberine exposure. In addition, a correlation between oxidative overload and
FoxO's nuclear accumulation via JNK activation was evident as berberine treatment
led to a pronounced increase in JNK phosphorylation together with enhanced ROS
generation, lipid peroxidation, decreased activities of superoxide dismutase and
catalase, and diminished glutathione levels. Thus, our findings suggest that the
antiproliferative effect of berberine may in part be due to mitochondria-mediated
apoptosis with Bim acting as a pivotal downstream factor of FoxO-induced
transcriptional activation.
PMID- 25128468
TI - Quality care outcomes following transitional care interventions for older people
from hospital to home: a systematic review.
AB - BACKGROUND: Provision of high quality transitional care is a challenge for health
care providers in many western countries. This systematic review was conducted to
(1) identify and synthesise research, using randomised control trial designs, on
the quality of transitional care interventions compared with standard hospital
discharge for older people with chronic illnesses, and (2) make recommendations
for research and practice. METHODS: Eight databases were searched; CINAHL,
Psychinfo, Medline, Proquest, Academic Search Complete, Masterfile Premier,
SocIndex, Humanities and Social Sciences Collection, in addition to the Cochrane
Collaboration, Joanna Briggs Institute and Google Scholar. Results were screened
to identify peer reviewed journal articles reporting analysis of quality
indicator outcomes in relation to a transitional care intervention involving
discharge care in hospital and follow-up support in the home. Studies were
limited to those published between January 1990 and May 2013. Study participants
included people 60 years of age or older living in their own homes who were
undergoing care transitions from hospital to home. Data relating to study
characteristics and research findings were extracted from the included articles.
Two reviewers independently assessed studies for risk of bias. RESULTS: Twelve
articles met the inclusion criteria. Transitional care interventions reported in
most studies reduced re-hospitalizations, with the exception of general
practitioner and primary care nurse models. All 12 studies included outcome
measures of re-hospitalization and length of stay indicating a quality focus on
effectiveness, efficiency, and safety/risk. Patient satisfaction was assessed in
six of the 12 studies and was mostly found to be high. Other outcomes reflecting
person and family centred care were limited including those pertaining to the
patient and carer experience, carer burden and support, and emotional support for
older people and their carers. Limited outcome measures were reported reflecting
timeliness, equity, efficiencies for community providers, and symptom management.
CONCLUSIONS: Gaps in the evidence base were apparent in the quality domains of
timeliness, equity, efficiencies for community providers, effectiveness/symptom
management, and domains of person and family centred care. Further research that
involves the person and their family/caregiver in transitional care interventions
is needed.
PMID- 25128469
TI - Love-Hate ligands for high resolution analysis of strain in ultra-stable
protein/small molecule interaction.
AB - The pathway of ligand dissociation and how binding sites respond to force are not
well understood for any macromolecule. Force effects on biological receptors have
been studied through simulation or force spectroscopy, but not by high resolution
structural experiments. To investigate this challenge, we took advantage of the
extreme stability of the streptavidin-biotin interaction, a paradigm for
understanding non-covalent binding as well as a ubiquitous research tool. We
synthesized a series of biotin-conjugates having an unchanged strong-binding
biotin moiety, along with pincer-like arms designed to clash with the protein
surface: 'Love-Hate ligands'. The Love-Hate ligands contained various 2,6-di
ortho aryl groups, installed using Suzuki coupling as the last synthetic step,
making the steric repulsion highly modular. We determined binding affinity, as
well as solving 1.1-1.6A resolution crystal structures of streptavidin bound to
Love-Hate ligands. Striking distortion of streptavidin's binding contacts was
found for these complexes. Hydrogen bonds to biotin's ureido and thiophene rings
were preserved for all the ligands, but biotin's valeryl tail was distorted from
the classic conformation. Streptavidin's L3/4 loop, normally forming multiple
energetically-important hydrogen bonds to biotin, was forced away by clashes with
Love-Hate ligands, but Ser45 from L3/4 could adapt to hydrogen-bond to a
different part of the ligand. This approach of preparing conflicted ligands
represents a direct way to visualize strained biological interactions and test
protein plasticity.
PMID- 25128470
TI - Intranasal nerve growth factor attenuates tau phosphorylation in brain after
traumatic brain injury in rats.
AB - Traumatic brain injury (TBI) is a considerable cause of mild cognitive impairment
and dementia. Intranasal administration of nerve growth factor (NGF) has
previously been found to improve cognitive function after TBI, but the mechanism
remains unclear. This study aimed to investigate the effects of intranasal NGF on
the tau hyperphosphorylation following TBI. A modified Feeney's weight-drop model
was used to induce TBI. Rats were randomly divided into control group, TBI group,
TBI+NGF group, TBI+PDTC group and TBI+IL-1ra group. Rats in TBI+NGF group were
administered with NGF (5 MUg/d) for 3d before surgery. Hyperphosphorylated tau
protein was remarkable in the peri-contusional cortex area with TBI. Both western
blotting and immunostaining results displayed intranasal pretreatment of NGF
significantly reduced tau phosphorylation. To evaluate the underlying mechanism,
the levels of glycogen synthase kinase 3beta (GSK-3beta), interleukin-1beta (IL
1beta), and the DNA binding activity of nuclear factor-kappaB (NF-kappaB) were
assayed. NGF markedly inhibited GSK-3beta. NGF also reduced TBI-induced elevation
of IL-1beta and NF-kappaB DNA binding activity. Furthermore, PDTC and IL-1ra were
injected to prove a potential signaling pathway among NF-kappaB, IL-1beta and GSK
3beta. Taken together, these findings demonstrated that intranasal NGF could
effectively attenuate the hyperphosphorylation of tau after TBI, which might
involve an integrated signaling pathway related to NF-kappaB.
PMID- 25128471
TI - Familial acute necrotizing encephalopathy due to mutation in the RANBP2 gene.
AB - BACKGROUND: Acute necrotizing encephalopathy (ANE) is a rare and severe
parainfectious central nervous system disease in which previously healthy
children develop rapidly progressive coma following viral illness. While most ANE
are sporadic, familial autosomal dominant ANE due to mutations in the RANBP2 gene
has been recently reported (ANE1 or infection-induced acute encephalopathy-3
(IIAE3)). To date, only few IIAE3 families with ADANE episodes have been
described. OBJECTIVE: To report a new family with ADANE, describe clinical and
radiological features and discuss differential diagnosis including Leigh syndrome
or multiple sclerosis. OBSERVATION: The family included 3 symptomatic individuals
and one 59 year-old asymptomatic obligate carrier. Patients presented acute
episodes of encephalopathy few days after common viral infection. Ages of onset
ranged from 6 months to 5 years. Episodes not only occurred in childhood but also
recurred in adulthood. Initial neurological signs included coma, focal
neurological deficits and seizures. MRI showed typical necrotizing lesions
primarily in the thalamus and brainstem, and in the temporal lobes and insula.
CSF cell count and cultures were normal during episodes. RANBP2 gene screening
identified pathogenic heterozygous c.1754C>T mutation (p.Thr585Met). Episodes led
to cognitive or physical handicap in 2 patients and were fatal in one child.
CONCLUSION: IIAE3 or ADANE due to RANBP2 mutations has a large clinical
heterogeneity. Our family illustrates the associated phenotypes from asymptomatic
carrier to severe episodes of encephalopathy. Based on MRI features, the genetic
IIAE3 diagnosis is important since prophylaxis and symptomatic management of
infections may be beneficial, possibly in association with steroid or
gammaglobulins.
PMID- 25128472
TI - Muscle and nerve inflammation in intensive care unit-acquired weakness: a
systematic translational review.
AB - BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is an important
complication of critical illness. The main risk factors, sepsis and the systemic
inflammatory response syndrome, suggest an inflammatory pathogenesis. In this
systematic translational review we summarize current knowledge on inflammation in
muscle and nerve tissue in animal models of ICU-AW and in critically ill patients
with ICU-AW. METHODS: We conducted a systematic search in the databases of
MEDLINE, EMBASE and Web of Science using predefined search and selection
criteria. From the included studies we extracted data on study characteristics
and on inflammation in muscle and nerve tissue. RESULTS: The literature search
yielded 349 unique articles, of which 12 animal studies and 20 human studies
fulfilled the in- and exclusion criteria. All studies had important shortcomings
in methodological quality. In the animal studies, inflammation of muscle tissue
was found, represented by cellular infiltration and increased local levels of
various inflammatory mediators. In human studies, high levels of various
inflammatory mediators were found in muscle and nerve tissue of ICU-AW patients.
CONCLUSION: This systematic translational review suggests a role for local
inflammation in ICU-AW, but the available evidence is limited and studies have
severe methodological limitations.
PMID- 25128474
TI - Lack of angiopoietin-like-2 expression limits the metabolic stress induced by a
high-fat diet and maintains endothelial function in mice.
AB - BACKGROUND: Angiopoietin-like-2 (angptl2) is produced by several cell types
including endothelial cells, adipocytes and macrophages, and contributes to the
inflammatory process in cardiovascular diseases. We hypothesized that angptl2
impairs endothelial function, and that lowering angptl2 levels protects the
endothelium against high-fat diet (HFD)-induced fat accumulation and
hypercholesterolemia. METHODS AND RESULTS: Acute recombinant angptl2 reduced
(P<0.05) acetylcholine-mediated vasodilation of isolated wild-type (WT) mouse
femoral artery, an effect reversed (P<0.05) by the antioxidant N-acetylcysteine.
Accordingly, in angptl2 knockdown (KD) mice, ACh-mediated endothelium-dependent
vasodilation was greater (P<0.05) than in WT mice. In arteries from KD mice,
prostacyclin contributed to the overall dilation unlike in WT mice. After a 3
month HFD, overall vasodilation was not altered, but dissecting out the
endothelial intrinsic pathways revealed that NO production was reduced in
arteries isolated from HFD-fed WT mice (P<0.05), while NO release was maintained
in KD mice. Similarly, endothelium-derived hyperpolarizing factor (EDHF) was
preserved in mesenteric arteries from HFD-fed KD mice but not in those from WT
mice. Finally, the HFD increased (P<0.05) total cholesterol-to-high-density
lipoprotein ratios, low-density lipoprotein-to-high-density lipoprotein ratios,
and leptin levels in WT mice only, while glycemia remained similar in the 2
strains. KD mice displayed less triglyceride accumulation in the liver (P<0.05
versus WT), and adipocyte diameters in mesenteric and epididymal white adipose
tissues were smaller (P<0.05) in KD than in WT fed an HFD, while inflammatory
gene expression increased (P<0.05) in the fat of WT mice only. CONCLUSIONS: Lack
of angptl2 expression limits the metabolic stress induced by an HFD and maintains
endothelial function in mice.
PMID- 25128476
TI - The impact of previous hospitalization in the preceding 90 days on the outcome in
critically ill patients with gram-negative bloodstream infection.
AB - We conducted a retrospective cohort study to evaluate the impact of previous
hospitalization in the preceding 90 days on mortality in critically ill patients
with gram-negative bloodstream infection (BSI) and to identify the risk factors
for 30-day mortality in these patients. Of 89 critically ill patients with gram
negative BSI, 42 patients had previous hospitalization in the preceding 90 days.
Multivariate Cox regression analysis revealed previous hospitalization in the
preceding 90 days as a significant predictor for 30-day mortality (hazard ratio
[HR], 2.10; 95% confidence interval [CI], 1.11-3.94; P = 0.022), along with Acute
Physiology and Chronic Health Evaluation II score at BSI onset (HR, 1.08; 95% CI,
1.04-1.12; P < 0.001), liver cirrhosis (HR, 3.61; 95% CI, 1.46-8.94; P = 0.006),
and inappropriate definitive antimicrobial therapy (HR, 4.28; 95% CI, 2.17-8.45;
P < 0.001). The effect of previous hospitalization in the preceding 90 days
should be considered in evaluating the risk for 30-day mortality when treating
such patients, and further study is required.
PMID- 25128475
TI - Transcriptomic analysis of Clostridium thermocellum Populus hydrolysate-tolerant
mutant strain shows increased cellular efficiency in response to Populus
hydrolysate compared to the wild type strain.
AB - BACKGROUND: The thermophilic, anaerobic bacterium, Clostridium thermocellum is a
model organism for consolidated processing due to its efficient fermentation of
cellulose. Constituents of dilute acid pretreatment hydrolysate are known to
inhibit C. thermocellum and other microorganisms. To evaluate the biological
impact of this type of hydrolysate, a transcriptomic analysis of growth in
hydrolysate-containing medium was conducted on 17.5% v/v Populus hydrolysate
tolerant mutant (PM) and wild type (WT) strains of C. thermocellum. RESULTS: In
two levels of Populus hydrolysate medium (0% and 10% v/v), the PM showed both
gene specific increases and decreases of gene expression compared to the wild
type strain. The PM had increased expression of genes in energy production and
conversion, and amino acid transport and metabolism in both standard and 10% v/v
Populus hydrolysate media. In particular, expression of the histidine metabolism
increased up to 100 fold. In contrast, the PM decreased gene expression in cell
division and sporulation (standard medium only), cell defense mechanisms, cell
envelope, cell motility, and cellulosome in both media. The PM downregulated
inorganic ion transport and metabolism in standard medium but upregulated it in
the hydrolysate media when compared to the WT. The WT differentially expressed
1072 genes in response to the hydrolysate medium which included increased
transcription of cell defense mechanisms, cell motility, and cellulosome, and
decreased expression in cell envelope, amino acid transport and metabolism,
inorganic ion transport and metabolism, and lipid metabolism, while the PM only
differentially expressed 92 genes. The PM tolerates up to 17.5% v/v Populus
hydrolysate and growth in it elicited 489 genes with differential expression,
which included increased expression in energy production and conversion,
cellulosome production, and inorganic ion transport and metabolism and decreased
expression in transcription and cell defense mechanisms. CONCLUSION: These
results suggest the mechanisms of tolerance for the Populus hydrolysate-tolerant
mutant strain of C. thermocellum are based on increased cellular efficiency
caused apparently by downregulation of non-critical genes and increasing the
expression of genes in energy production and conversion rather than tolerance to
specific hydrolysate components. The wild type, conversely, responds to
hydrolysate media by down-regulating growth genes and up-regulating stress
response genes.
PMID- 25128477
TI - Ceftazidime-avibactam and comparator agents tested against urinary tract isolates
from a global surveillance program (2011).
AB - Ceftazidime-avibactam, a combination of ceftazidime and the non-beta-lactam beta
lactamase inhibitor avibactam, is in advanced clinical development. In this
study, we report results of in vitro testing of ceftazidime-avibactam and
comparator agents against a collection of urinary tract infection (UTI) isolates
from the United States (USA), Europe and Mediterranean region (EMR), Latin
America (LATAM), and the Asia-Pacific/South Africa regions (APAC). Clinical
isolates (1 per patient episode) were collected from patients with a UTI during
2011. A total of 1797 isolates were collected from 159 medical centers. Isolates
were processed at the medical centers and forwarded to a central monitoring
laboratory for confirmatory identification and reference susceptibility testing.
Ceftazidime-avibactam was highly active against Enterobacteriaceae and
Pseudomonas aeruginosa. The MIC90 values for ceftazidime-avibactam against
Enterobacteriaceae in the USA, EMR, and LATAM regions ranged from 0.25 to
0.5MUg/mL. The MIC90 in the APAC was slightly elevated at 1MUg/mL. A total of
6.1% (8/131) of Escherichia coli in the USA, 23.5% (43/183) in the EMR, 61.2%
(30/49) in LATAM, and 75.0% (9/12) in APAC exhibited an extended-spectrum beta
lactamase (ESBL) screen-positive phenotype. A total of 1.6% (2/129) of Klebsiella
pneumoniae isolates in the USA were meropenem-non-susceptible (MIC >=2MUg/mL),
but a rate of 10.3% (10/97) was observed in the EMR. All ESBL screen-positive
phenotype and meropenem-non-susceptible E. coli and K. pneumoniae isolates
exhibited a ceftazidime-avibactam MIC <=4MUg/mL. All isolates of P. aeruginosa in
the USA and 80.9% (38/47) in the EMR were inhibited at a ceftazidime-avibactam
MIC of <=8MUg/mL compared to 88.2% (15/17) and 61.7% (29/47) for ceftazidime
alone. Ceftazidime-avibactam demonstrated wide in vitro activity against Gram
negative bacteria from patients with UTI including high potencies against
multidrug-resistant organisms.
PMID- 25128478
TI - Genome wide CNV analysis reveals additional variants associated with milk
production traits in Holsteins.
AB - BACKGROUND: Milk production is an economically important sector of global
agriculture. Much attention has been paid to the identification of quantitative
trait loci (QTL) associated with milk, fat, and protein yield and the genetic and
molecular mechanisms underlying them. Copy number variation (CNV) is an emerging
class of variants which may be associated with complex traits. RESULTS: In this
study, we performed a genome-wide association between CNVs and milk production
traits in 26,362 Holstein bulls and cows. A total of 99 candidate CNVs were
identified using Illumina BovineSNP50 array data, and association tests for each
production trait were performed using a linear regression analysis with PCA
correlation. A total of 34 CNVs on 22 chromosomes were significantly associated
with at least one milk production trait after false discovery rate (FDR)
correction. Some of those CNVs were located within or near known QTL for milk
production traits. We further investigated the relationship between associated
CNVs with neighboring SNPs. For all 82 combinations of traits and CNVs (less than
400 kb in length), we found 17 cases where CNVs directly overlapped with tag SNPs
and 40 cases where CNVs were adjacent to tag SNPs. In 5 cases, CNVs located were
in strong linkage disequilibrium with tag SNPs, either within or adjacent to the
same haplotype block. There were an additional 20 cases where CNVs did not have a
significant association with SNPs, suggesting that the effects of those CNVs were
probably not captured by tag SNPs. CONCLUSION: We conclude that combining CNV
with SNP analyses reveals more genetic variations underlying milk production
traits than those revealed by SNPs alone.
PMID- 25128479
TI - Opportunities and challenges in implementing community based skilled birth
attendance strategy in Kenya.
AB - BACKGROUND: Availability of skilled care at birth remains a major problem in most
developing countries. In an effort to increase access to skilled birth
attendance, the Kenyan government implemented the community midwifery programme
in 2005. The aim of this programme was to increase women's access to skilled care
during pregnancy, childbirth and post-partum within their communities. METHODS:
Qualitative research involving in-depth interviews with 20 community midwives and
six key informants. The key informants were funder, managers, coordinators and
supervisors of the programme. Interviews were conducted between June to July,
2011 in two districts in Western and Central provinces of Kenya. RESULTS:
Findings showed major challenges and opportunities in implementing the community
midwifery programme. Challenges of the programme were: socio-economic issues,
unavailability of logistics, problems of transportation for referrals and
insecurity. Participants also identified the advantages of having midwives in the
community which were provision of individualised care; living in the same
community with clients which made community midwives easily accessible; and
flexible payment options. CONCLUSIONS: Although the community midwifery model is
a culturally acceptable method to increase skilled birth attendance in Kenya, the
use of skilled birth attendance however remains disproportionately lower among
poor mothers. Despite several governmental efforts to increase access and
coverage of delivery services to the poor, it is clear that the poor may still
not access skilled care even with skilled birth attendants residing in the
community due to several socio-economic barriers.
PMID- 25128480
TI - Spatiotemporal analysis of sandfly fauna (Diptera: Psychodidae) in an endemic
area of visceral leishmaniasis at Pantanal, central South America.
AB - BACKGROUND: Environmental changes caused by urbanization can cause alterations in
the ecology and behavior of sandflies and in the epidemiology of leishmaniasis.
Geotechnological tools allow the analysis and recognition of spatiotemporal
patterns by monitoring and mapping risk areas of this vector-borne disease. This
study aims to describe the sandfly fauna in the municipality of Corumba and to
compare it with the data described in a three-year period from 1984 to 1986 by
Galati. A further aim was to analyze the influence of environmental changes on
the composition of the fauna. METHODS: Captures were conducted weekly from April
2012 to March 2013, in intra and peridomicile areas with automatic light traps,
from 6:00 pm to 6:00 am. The following indices were calculated for both periods
analyzed: Standardized Index of Species Abundance (SISA), Shannon's diversity
index (H) and Pielou's index (J). The Normalized Difference Vegetation Index
(NDVI) was extracted from a remote sensing LANDSAT-5 image. RESULTS: In total,
7,370 specimens (6,169 males and 1,201 females) were collected, distributed among
12 species. Lutzomyia cruzi was the most frequent species (93,79%) and the first
in the ranking of standardized species abundance index in both studies. The
dominance of the species Lu. cruzi in the neighborhoods of Maria Leite and Centro
was demonstrated by the low equitability index. The neighborhood of Cristo
Redentor had the greatest diversity of sandflies in the present study and the
second greatest in the study performed by Galati et al. (Rev Saude Publica 31:378
390, 1997). Analyzing the satellite images and the NDVI from 1984 and 2010, the
largest amount of dense vegetation was found in the neighborhood of Cristo
Redentor. CONCLUSIONS: It was, therefore, possible to show how changes caused due
to urbanization have affected the density and distribution of Lu. cruzi and other
species over time. Moreover, the data suggest that different populations of
sandflies adapt in different ways according to environmental conditions and the
adaptation does not necessarily depends on the presence of high vegetation cover.
PMID- 25128481
TI - Sleep and body mass index in adolescence: results from a large population-based
study of Norwegian adolescents aged 16 to 19 years.
AB - BACKGROUND: The aim of this study was to examine the association between body
mass index (BMI) and sleep duration, insomnia and symptoms of obstructive sleep
apnea (OSA) in adolescents. METHODS: Data were taken from a large population
based study of 9,875 Norwegian adolescents aged 16-19. BMI was calculated from
the self-reported body weight and categorized according to recommended age and
gender specific cut offs for underweight, overweight and obesity. Detailed sleep
parameters (sleep duration, insomnia, and OSA symptoms) were reported separately
for weekdays and weekends. Data were analyzed using Pearson's chi-squared test
and ANOVAs for simple categorical and continuous comparisons, and multinomial
logistic regressions for analyses adjusting for known confounders. RESULTS: There
was evidence for a curvilinear relationship between BMI and both sleep duration
and insomnia for girls, whereas the relationship was linear for boys. Compared to
the average weekday sleep duration among adolescents in the normal weight range
(6 hrs 29 min), both underweight (5 hrs 48 min), overweight (6 hrs 13 min) and
obese (5 hrs 57 min) adolescents had shorter sleep duration. OSA symptoms were
linearly associated with BMI. Controlling for demographical factors as well as
physical activity did not attenuate the associations. Additional adjustment for
depression reduced the association between insomnia and obesity to a non
significant level. The evidence for a link between both underweight and
overweight/obesity, and short sleep duration and OSA symptoms remained in the
fully adjusted analyses. The associations were generally stronger for girls.
CONCLUSIONS: This is one of the first population-based studies to investigate the
relationship between sleep and BMI in adolescents while simultaneously
controlling for important confounding factors. These findings require further
research to investigate the temporal association between weights and sleep
problems.
PMID- 25128482
TI - The effect of CTLA-4 A49G polymorphism on rheumatoid arthritis risk: a meta
analysis.
AB - BACKGROUND: Recently, a number of studies have been performed to explore the
association between CTLA-4 A49G polymorphism and rheumatoid arthritis (RA).
However, the results of previous works are still controversial and ambiguous.
METHODS: In this work, we attempted to perform an updated meta-analysis of
available case-control study in order to assess the association between CTLA-4
A49G polymorphism and RA risk. We searched the various citation databases without
limits on languages. Article searching was performed by screening the references
of retrieved studies manually. Odds ratios (OR) and 95% confidence intervals (95%
CI) were calculated to evaluate the strength of the association. RESULTS: We
totally compiled 27 studies in 24 articles (9805 RA patients and 10691 control
subjects) into our meta-analysis work. We found significant association between
CTL-A4 A49G polymorphism and RA risk (GG vs. AA: OR = 1.13, 95% CI = 1.03-1.23;
GA vs. AA: OR = 1.19, 95% CI = 1.07-1.33; GA + GG vs. AA: OR = 1.18, 95% CI =
1.07-1.29). In the subgroup analysis by ethnicity, evidences of significantly
increased risk was also found in both Asian (GG vs. AA: OR = 1.34, 95% CI = 1.15
1.55; GA + GG vs. AA: OR = 1.24, 95% CI = 1.08-1.41) and Caucasian population (GA
vs. AA: OR = 1.19, 95% CI = 1.03-1.37; GA + GG vs. AA: OR = 1.14, 95% CI = 1.01
1.29). No evidence of publication bias was found in this work. CONCLUSIONS: Our
meta-analysis suggests that CTLA-4 A49G polymorphism was associated with RA risk.
VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_157.
PMID- 25128484
TI - Overweight and obesity are linked to 10 common cancers and more than 12,000 UK
cases.
PMID- 25128483
TI - miR-27a regulates cisplatin resistance and metastasis by targeting RKIP in human
lung adenocarcinoma cells.
AB - BACKGROUND: MicroRNAs (miRNAs) have been identified as important
posttranscriptional regulators involved in various biological and pathological
processes of cells, but their association with tumor chemoresistance has not been
fully understood. METHODS: We detected miR-27a expression in two lung
adenocarcinoma cell lines, A549 and A549/CDDP, and then investigated the effects
of miR-27a on the metastasis and the chemosensitivity of cancer cells, using both
gain- and loss-of-function studies. The correlation between miR-27a level and
chemoresistance was further investigated in clinical lung adenocarcinoma
specimens. RESULTS: miR-27a was significantly up-regulated in cisplatin-resistant
lung adenocarcinoma A549/CDDP cells compared with parental A549 cells. miR-27a
regulates epithelial-mesenchymal transition (EMT) and cisplatin resistance in
vitro and modulates response of lung adenocarcinoma cells to cisplatin in vivo.
Further studies identified Raf Kinase Inhibitory Protein (RKIP) as a direct and
functional target of miR-27a. Small interfering RNA-mediated RKIP knockdown
revealed similar effects as that of ectopic miR-27a expression, while
overexpression of RKIP attenuated the function of miR-27a in lung adenocarcinoma
cells. Increased miR-27a expression was also detected in tumor tissues sampled
from lung adenocarcinoma patients treated with cisplatin-based chemotherapy and
was proved to be correlated with low expression of RKIP, decreased sensitivity to
cisplatin, and poor prognosis. CONCLUSION: Our results suggest that up-regulation
of miR-27a could suppress RKIP expression and in turn contribute to
chemoresistance of lung adenocarcinoma cells to cisplatin.
PMID- 25128485
TI - Unfractionated heparin and placental pathology in high-risk pregnancies:
secondary analysis of a pilot randomized controlled trial.
AB - INTRODUCTION: Heparin is often prescribed during pregnancy with the intention of
improving perinatal outcomes on the basis that it exerts an anticoagulant action
in the inter-villous space. Accumulating in-vitro and in-vivo evidence indicates
that heparin's beneficial effects in pregnancy may result from 'non
anticoagulant' effects including the promotion of angiogenesis. METHODS: To study
the effect of heparin within the placenta, we performed secondary analyses on a
pilot trial where 32 women with negative thrombophilia screens and second
trimester evidence of placental insufficiency were randomized to standard care or
antenatal self-administration of unfractionated heparin (UFH) 7500 IU twice
daily. Serial placental ultrasound images were reviewed and compared with histo
pathologic findings following delivery. RESULTS: There were no differences
between the two arms in either the evolution of abnormal placental lesions on
ultrasound (p = 0.75) or evidence of maternal vascular under-perfusion on
histopathology (p = 0.89). In pregnancies considered at increased risk for
adverse pregnancy outcomes based on previous history or abnormal serum marker
screen, early (second-trimester) placental ultrasound, reflecting developmental
pathology had better test characteristics (sensitivity 77.8%; positive predictive
value 80.8%) for predicting adverse pregnancy outcomes than third-trimester
ultrasound that is reflective of placental thrombotic injury. CONCLUSIONS:
Administration of UFH did not prevent the development or evolution of abnormal
placental lesions on placental ultrasound or evidence of maternal vascular
underperfusion on placental histo-pathology. Second-trimester placental
ultrasound may be of value in predicting those at greatest risk of adverse
outcomes.
PMID- 25128486
TI - Report of the independent panel considering the retraction of two articles in The
BMJ.
PMID- 25128487
TI - UK government may face legal challenge from Philip Morris over plain cigarette
packaging.
PMID- 25128488
TI - The fight is on: military metaphors for cancer may harm patients.
PMID- 25128493
TI - How substrate specificity is imposed on a histone demethylase--lessons from
KDM2A.
AB - Histone lysine methylation and demethylation regulate histone methylation
dynamics, which impacts chromatin structure and function. To read and erase the
methylated histone residues, lysine demethylases must specifically recognize the
histone sequences and methylated sites and discriminate the degree of these
methylations. In this issue of Genes & Development, Cheng and colleagues (pp.
1758-1771) determine a crystal structure of histone lysine demethylase KDM2A that
specifically targets lower degrees of H3K36 methylation. The results reveal the
structural basis for H3K36 substrate specificity and suggest mechanisms of Lys36
demethylation. This KDM2A-H3K36 complex structure, coupled with functional
studies, provides needed insight into the process and regulation of histone
demethylation.
PMID- 25128495
TI - Small intestinal stem cell identity is maintained with functional Paneth cells in
heterotopically grafted epithelium onto the colon.
AB - To develop stem cell therapy for small intestinal (SI) diseases, it is essential
to determine whether SI stem cells in culture retain their tissue regeneration
capabilities. By using a heterotopic transplantation approach, we show that
cultured murine SI epithelial organoids are able to reconstitute self-renewing
epithelia in the colon. When stably integrated, the SI-derived grafts show many
features unique only to the SI but distinct from the colonic epithelium. Our
study provides evidence that cultured adult SI stem cells could be a source for
cell therapy of intestinal diseases, maintaining their identity along the
gastrointestinal tract through an epithelium-intrinsic mechanism.
PMID- 25128494
TI - Limiting the power of p53 through the ubiquitin proteasome pathway.
AB - The ubiquitin proteasome pathway is critical in restraining the activities of the
p53 tumor suppressor. Numerous E3 and E4 ligases regulate p53 levels.
Additionally, deubquitinating enzymes that modify p53 directly or indirectly also
impact p53 function. When alterations of these proteins result in increased p53
activity, cells arrest in the cell cycle, senesce, or apoptose. On the other
hand, alterations that result in decreased p53 levels yield tumor-prone
phenotypes. This review focuses on the physiological relevance of these important
regulators of p53 and their therapeutic implications.
PMID- 25128496
TI - A molecular threading mechanism underlies Jumonji lysine demethylase KDM2A
regulation of methylated H3K36.
AB - The dynamic reversible methylation of lysine residues on histone proteins is
central to chromatin biology. Key components are demethylase enzymes, which
remove methyl moieties from lysine residues. KDM2A, a member of the Jumonji C
domain-containing histone lysine demethylase family, specifically targets lower
methylation states of H3K36. Here, structural studies reveal that H3K36
specificity for KDM2A is mediated by the U-shaped threading of the H3K36 peptide
through a catalytic groove within KDM2A. The side chain of methylated K36 inserts
into the catalytic pocket occupied by Ni(2+) and cofactor, where it is positioned
and oriented for demethylation. Key residues contributing to K36me specificity on
histone H3 are G33 and G34 (positioned within a narrow channel), P38 (a turn
residue), and Y41 (inserts into its own pocket). Given that KDM2A was found to
also bind the H3K36me3 peptide, we postulate that steric constraints could
prevent alpha-ketoglutarate from undergoing an "off-line"-to-"in-line" transition
necessary for the demethylation reaction. Furthermore, structure-guided
substitutions of residues in the KDM2A catalytic pocket abrogate KDM2A-mediated
functions important for suppression of cancer cell phenotypes. Together, our
results deduce insights into the molecular basis underlying KDM2A regulation of
the biologically important methylated H3K36 mark.
PMID- 25128497
TI - CDK9-mediated transcription elongation is required for MYC addiction in
hepatocellular carcinoma.
AB - One-year survival rates for newly diagnosed hepatocellular carcinoma (HCC) are
<50%, and unresectable HCC carries a dismal prognosis owing to its aggressiveness
and the undruggable nature of its main genetic drivers. By screening a custom
library of shRNAs directed toward known drug targets in a genetically defined Myc
driven HCC model, we identified cyclin-dependent kinase 9 (Cdk9) as required for
disease maintenance. Pharmacological or shRNA-mediated CDK9 inhibition led to
robust anti-tumor effects that correlated with MYC expression levels and depended
on the role that both CDK9 and MYC exert in transcription elongation. Our results
establish CDK9 inhibition as a therapeutic strategy for MYC-overexpressing liver
tumors and highlight the relevance of transcription elongation in the addiction
of cancer cells to MYC.
PMID- 25128498
TI - The FACT complex interacts with the E3 ubiquitin ligase Psh1 to prevent ectopic
localization of CENP-A.
AB - Centromere identity and its epigenetic maintenance require the incorporation of a
histone H3 variant called CENP-A at centromeres. CENP-A mislocalization to
ectopic sites may disrupt chromatin-based processes and chromosome segregation,
so it is important to uncover the mechanisms by which this variant is exclusively
localized to centromeres. Here, we identify a role for the conserved chromatin
modifying complex FACT (facilitates chromatin transcription/transactions) in
preventing budding yeast CENP-A(Cse4) mislocalization to euchromatin by mediating
its proteolysis. The Spt16 subunit of the FACT complex binds to Psh1
(Pob3/Spt16/histone), an E3 ubiquitin ligase that targets CENP-A(Cse4) for
degradation. The interaction between Psh1 and Spt16 is critical for both CENP
A(Cse4) ubiquitylation and its exclusion from euchromatin. We found that Psh1
cannot efficiently ubiquitylate CENP-A(Cse4) nucleosomes in vitro, suggesting
that additional factors must facilitate CENP-A(Cse4) removal from chromatin in
vivo. Consistent with this, a Psh1 mutant that cannot associate with FACT has a
reduced interaction with CENP-A(Cse4) in vivo. Together, our data identify a
previously unknown mechanism to maintain centromere identity and genomic
stability through the FACT-mediated degradation of ectopically localized CENP
A(Cse4).
PMID- 25128501
TI - Retraction.
PMID- 25128499
TI - Active enhancers are delineated de novo during hematopoiesis, with limited
lineage fidelity among specified primary blood cells.
AB - Tissues may adopt diverse strategies to establish specific transcriptional
programs in daughter lineages. In intestinal crypts, enhancers for genes
expressed in both major cell types appear broadly permissive in stem and
specified progenitor cells. In blood, another self-renewing tissue, it is unclear
when chromatin becomes permissive for transcription of genes expressed in
distinct terminal lineages. Using chromatin immunoprecipitation (ChIP) combined
with deep sequencing (ChIP-seq) to profile activating histone marks, we studied
enhancer dynamics in primary mouse blood stem, progenitor, and specified cells.
Stem and multipotent progenitor cells show scant H3K4me2 marking at enhancers
bound by specific transcription factors in their committed progeny. Rather,
enhancers are modulated dynamically and serially, with substantial loss and gain
of H3K4me2, at each cellular transition. Quantitative analysis of these dynamics
accurately modeled hematopoiesis according to Waddington's notion of
epigenotypes. Delineation of enhancers in terminal blood lineages coincides with
cell specification, and enhancers active in single lineages show well-positioned
H3K4me2- and H3K27ac-marked nucleosomes and DNaseI hypersensitivity in other cell
types, revealing limited lineage fidelity. These findings demonstrate that
enhancer chronology in blood cells differs markedly from that in intestinal
crypts. Chromatin dynamics in hematopoiesis provide a useful foundation to
consider classical observations such as cellular reprogramming and multilineage
locus priming.
PMID- 25128502
TI - In silico prediction of major drug clearance pathways by support vector machines
with feature-selected descriptors.
AB - We have previously established an in silico classification method ("CPathPred")
to predict the major clearance pathways of drugs based on an empirical decision
with only four physicochemical descriptors-charge, molecular weight, octanol
water distribution coefficient, and protein unbound fraction in plasma-using a
rectangular method. In this study, we attempted to improve the prediction
performance of the method by introducing a support vector machine (SVM) and
increasing the number of descriptors. The data set consisted of 141 approved
drugs whose major clearance pathways were classified into metabolism by CYP3A4,
CYP2C9, or CYP2D6; organic anion transporting polypeptide-mediated hepatic
uptake; or renal excretion. With the same four default descriptors as used in
CPathPred, the SVM-based predictor (named "default descriptor SVM") resulted in
higher prediction performance compared with a rectangular-based predictor judged
by 10-fold cross-validation. Two SVM-based predictors were also established by
adding some descriptors as follows: 1) 881 descriptors predicted in silico from
the chemical structures of drugs in addition to 4 default descriptors ("885
descriptor SVM"); and 2) selected descriptors extracted by a feature selection
based on a greedy algorithm with default descriptors ("feature selection SVM").
The prediction accuracies of the rectangular-based predictor, default descriptor
SVM, 885 descriptor SVM, and feature selection SVM were 0.49, 0.60, 0.72, and
0.91, respectively, and the overall precision values for these four methods were
0.72, 0.77, 0.86, and 0.98, respectively. In conclusion, we successfully
constructed SVM-based predictors with limited numbers of descriptors to classify
the major clearance pathways of drugs in humans with high prediction performance.
PMID- 25128500
TI - Incomplete replication generates somatic DNA alterations within Drosophila
polytene salivary gland cells.
AB - DNA replication remains unfinished in many Drosophila polyploid cells, which
harbor disproportionately fewer copies of late-replicating chromosomal regions.
By analyzing paired-end high-throughput sequence data from polytene larval
salivary gland cells, we define 112 underreplicated (UR) euchromatic regions 60
480 kb in size. To determine the effects of underreplication on genome integrity,
we analyzed anomalous read pairs and breakpoint reads throughout the euchromatic
genome. Each UR euchromatic region contains many different deletions 10-500 kb in
size, while very few deletions are present in fully replicated chromosome regions
or UR zones from embryo DNA. Thus, during endocycles, stalled forks within UR
regions break and undergo local repair instead of remaining stable and generating
nested forks. As a result, each salivary gland cell contains hundreds of unique
deletions that account for their copy number reductions. Similar UR regions and
deletions were observed in ovarian DNA, suggesting that incomplete replication,
fork breakage, and repair occur widely in polytene cells. UR regions are enriched
in genes encoding immunoglobulin superfamily proteins and contain many neurally
expressed and homeotic genes. We suggest that the extensive somatic DNA
instability described here underlies position effect variegation, molds the
structure of polytene chromosomes, and should be investigated for possible
functions.
PMID- 25128503
TI - Advance care planning: whose agenda is it anyway?
PMID- 25128505
TI - Infections increase risk of arterial and venous thromboses in Danish patients
with systemic lupus erythematosus: 5102 patient-years of followup.
AB - OBJECTIVE: Infections and thromboses are known complications of systemic lupus
erythematosus (SLE). We investigated if infectious episodes in patients with SLE
were followed by an increased risk of thrombotic events. METHODS: A cohort of 571
patients with prevalent or incident SLE was followed for a mean of 8.9 +/- 7.6
years. All episodes of hospitalized infections or episodes of cutaneous herpes
zoster as well as arterial and venous thrombotic events were identified by
retrospective chart review and prospective updating of a clinical database. For
time-dependent analyses adjusted for age, sex, and ever-presence of
antiphospholipid antibodies, thrombotic events were classified as occurring
during the time at risk of 1 year after an infection or during the remaining
control observation time. RESULTS: Of 271 infections identified, 104 were
respiratory, 41 cutaneous herpes zoster, and 126 others. Of 159 thromboses
identified, 98 were arterial. Incidence for arterial and venous thromboses within
1 year after infection was 2.18% and 2.56%, respectively, compared to patients
who never had an infection (0.58 and 0.67). The adjusted 1-year risk of arterial
and venous thrombosis after any infection was increased [relative rate (RR) 2.5,
95% CI 1.4-4.6, and RR 2.8, 95% CI 1.3-5.9, respectively]. Venous thromboses were
in particular more prevalent after respiratory infections (RR 5.4, 95% CI 2.3
13). CONCLUSION: The temporal associations observed in this study indicate that
infections could be risk factors for arterial or venous thromboses in patients
with SLE, although causality was not addressed by this study.
PMID- 25128504
TI - Serum 14-3-3eta is a novel marker that complements current serological
measurements to enhance detection of patients with rheumatoid arthritis.
AB - OBJECTIVE: Serum 14-3-3eta is a novel joint-derived proinflammatory mediator
implicated in the pathogenesis of rheumatoid arthritis (RA). In our study, we
assessed the diagnostic utility of 14-3-3eta and its association with standard
clinical and serological measures. METHODS: A quantitative ELISA was used to
assess 14-3-3eta levels. Early (n=99) and established patients with RA (n=135)
were compared to all controls (n=385), including healthy subjects (n=189). The
sensitivity, specificity, positive and negative predictive values of 14-3-3eta,
and the likelihood ratios (LR) for RA were determined through receiver-operator
curve analysis. The incremental value of adding 14-3-3eta to anticitrullinated
protein antibody (ACPA) and rheumatoid factor (RF) in diagnosing early and
established RA was assessed. RESULTS: Serum 14-3-3eta differentiated established
patients with RA from healthy individuals and all controls (p<0.0001). A serum 14
3-3eta cutoff of >=0.19 ng/ml delivered a sensitivity and specificity of 77% and
93%, respectively, with corresponding LR positivity of 10.4. At this cutoff in
early RA, 64% of patients with early RA were positive for 14-3-3eta, with a
corresponding specificity of 93% (LR+ of 8.6), while 59% and 57% were positive
for ACPA or RF, respectively. When ACPA, RF, and 14-3-3eta positivity were used
in combination, 77 of the 99 patients (78%) with early RA were positive for any 1
of the 3 markers. Serum 14-3-3eta did not correlate with C-reactive protein,
erythrocyte sedimentation rate, or Disease Activity Score, but patients who were
14-3-3eta-positive had significantly worse disease. CONCLUSION: Serum 14-3-3eta
is a novel RA mechanistic marker that is highly specific, associated with worse
disease, and complements current markers, enabling a more accurate diagnosis of
RA.
PMID- 25128507
TI - Is HLA-B27 increased in patients diagnosed with undifferentiated arthritis?
Results from the Leiden early arthritis cohort.
AB - OBJECTIVE: Undifferentiated arthritis (UA) is a common form of arthritis.
According to the Assessment of Spondyloarthritis international Society (ASAS)
criteria for peripheral spondyloarthritis (pSpA), HLA-B27 can be used to help
classify patients with pSpA. We tested whether HLA-B27 is increased in patients
diagnosed with UA. METHODS: Prevalence of HLA-B27 was compared between healthy
controls and patients with UA. SpA features were compared between HLA-B27
positive and -negative UA, and SpA. RESULTS: We found 10.1% of UA (38/375) versus
7.2% (403/5584) of controls were HLA-B27-positive (OR 1.5, 95% CI 1.0-2.1; p =
0.037). HLA-B27-positive patients with UA had more SpA features than HLA-B27
negative patients (mean 1.6, SD 1.0, and 0.9 SD 0.6; p < 0.001), but patients
with SpA had significantly more SpA features (mean 4.5, SD 1.5; p < 0.001).
Family history and preceding infection were features more common in HLA-B27
positive than in HLA-B27-negative UA (15.8% vs 1.3%, p = 0.04 and 15.8% vs 2.6%,
p = 0.04). After HLA-B27 testing, 21 additional patients (5.6%) with UA could
potentially have been classified with pSpA according to the ASAS criteria.
CONCLUSION: HLA-B27 is more common in patients with UA than in controls. However,
the yield of HLA-B27 testing in UA is low. Our results suggest that HLA-B27
testing should be reserved for patients with additional SpA features.
PMID- 25128506
TI - Longterm followup of rituximab therapy in patients with rheumatoid arthritis:
results from the Belgian MabThera in Rheumatoid Arthritis registry.
AB - OBJECTIVE: Our study reports the results of the MIRA (MabThera In Rheumatoid
Arthritis) registry, set up to collect data about clinical usage, patient
profile, and retention of rituximab (RTX) treatment in daily clinical practice in
Belgium. METHODS: Patients with active rheumatoid arthritis (RA) who failed at
least 1 anti-tumor necrosis factor (anti-TNF) treatment were included in our
study between November 2006 and October 2011. At baseline, demographics,
medication, disease history, disease activity, rheumatoid factor (RF), and
anticyclic citrullinated peptide antibodies (anti-CCP) status were recorded.
Evolution of the 28-joint Disease Activity Score (DAS28)-erythrocyte
sedimentation rate, retreatments, and reasons for therapy stop were followed
prospectively. RESULTS: The MIRA registry included 649 patients, with mean
disease duration of 12.8 +/- 0.4 years and DAS28 values at inclusion of 5.85 +/-
0.48. Patients received on average 2.82 +/- 0.07 (range 1-9) RTX treatments, over
a mean followup period of 93.1 +/- 2.6 weeks. At database lock, 433 patients
(66.7%) were still under RTX treatment, 182 (28.0%) had stopped treatment, and 34
(5.2%) were lost to followup. Ineffectiveness (n = 108, 59%) and safety concerns
(n = 39, 22%) were the most frequent reasons for discontinuing RTX therapy. From
2006 to 2011, RTX practice patterns clearly evolved toward RTX being started in
patients with a lower number of previously failed anti-TNF drugs and lower
baseline DAS28 values. A lower number of previous anti-TNF drugs, and positivity
for RF and anti-CCP, predicted more successful longterm treatment. RTX treatment
provided adequate longterm disease control. CONCLUSION: In our daily practice
study, RTX provided good longterm disease control and treatment retention in
refractory patients with RA. Over the years, rheumatologists tended to start this
treatment in patients with fewer previous anti-TNF treatments and lower disease
activity.
PMID- 25128508
TI - Percutaneous transluminal angioplasty for symptomatic pulmonary stenosis in
Takayasu arteritis.
AB - OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of
percutaneous transluminal angioplasty (PTA) for symptomatic pulmonary stenosis in
Takayasu arteritis (TA). METHODS: From January 2009 to December 2012, clinical
data of 14 patients [mean age 33.9 +/- 9.3 yrs; 11 patients female (78.6%)] with
symptomatic pulmonary stenosis in TA underwent PTA and were analyzed
prospectively. RESULTS: PTA was successfully performed in 22 lesions of 14
patients. Among those lesions, 18 were treated by PTA alone while the others were
treated with stent implantation. Three patients (21.4%) had reperfusion pulmonary
injury; 2 patients recovered completely while the other died of respiratory
failure 3 days after the procedure. Mean pulmonary arterial pressure (PAP)
decreased from 53.4 +/- 15.8 mmHg to 38.4 +/- 12.7 mmHg immediately after
intervention (p < 0.001). After an average of 29 months of followup, the New York
Heart Association functional class and 6-min walking distances improved while
mean PAP measured by echocardiography decreased significantly (compared with
baseline, all p < 0.01). One patient died of severe pulmonary infection and
cardiac shock at 28 months after the procedure. CONCLUSION: The study showed that
PTA improved subjective symptoms and objective variables of the patients with
symptomatic pulmonary stenosis in TA, with an acceptable mortality. PTA may be a
promising therapeutic strategy for symptomatic pulmonary stenosis in TA.
PMID- 25128509
TI - Current smoking is associated with incident ankylosing spondylitis -- the HUNT
population-based Norwegian health study.
AB - OBJECTIVE: Smoking contributes to progression of ankylosing spondylitis (AS).
Because smoking is also a risk factor for incident rheumatoid arthritis (RA) and
psoriatic arthritis, our aim was to test whether smoking habits are associated
with incident AS. METHODS: Using data from the HUNT health study of the entire
adult population of Nord-Trondelag, Norway, participants in HUNT2 (1995-1997) and
HUNT3 (2006-2008) were identified who reported a diagnosis of AS in HUNT3 but not
in HUNT2 (n = 107). Incident AS cases were compared with AS-unaffected
individuals (n = 35,278) in a case-control design. Participants with RA were
excluded. RESULTS: Present smoking was significantly associated with incident
self-reported AS in logistic regression adjusted for potential confounders (OR
1.99, 95% CI 1.28-3.11, p = 0.002). Previous smoking (OR 1.15, 95% CI 0.66-2.02,
p = 0.62) or total pack-years at HUNT2 (OR 1.01, 95% CI 0.99-1.04, p = 0.21) were
not significant. The association with present smoking remained significant in
various sensitivity analyses: including only cases with high probability of true
AS diagnosis (OR 1.82, 95% CI 1.03-3.19, p = 0.04); including only cases with AS
reported more than 3-5 years after HUNT2 (OR 2.34, 95% CI 1.09-5.03, p = 0.029),
or including only participants genotyped for HLA-B27 (94 cases and 859 controls)
adjusting for genotype (OR 1.79, 95% CI 1.04-2.85, p = 0.033). Hypertension was
also significantly associated with incident AS (OR from 1.65 to 2.81).
CONCLUSION: In the HUNT population-based study, incident AS was associated with
current smoking and hypertension. If verified in further studies, this suggests
that smoking should be discouraged in those at a higher AS risk, e.g., with a
family history or carrying HLA-B27.
PMID- 25128510
TI - The effect of exercise on sleep and fatigue in rheumatoid arthritis: a randomized
controlled study.
AB - OBJECTIVE: Sleep disturbance and chronic fatigue are common in rheumatoid
arthritis (RA) and contribute to disability, symptomatology, and healthcare use.
It has long been recognized in other populations that exercise can improve sleep
and diminish fatigue. The effect of exercise on sleep quality and fatigue in RA
has not been evaluated. METHODS: Ours is a randomized controlled study in RA to
determine the effect of an exercise program on sleep quality and fatigue. These
were measured using the Pittsburgh Sleep Quality Index and the Fatigue Severity
Scale. Patients were randomized to either a 12-week, home-based exercise
intervention or usual care. The exercise program consisted of specific exercises
to target individual deficiencies identified using the Health Assessment
Questionnaire (HAQ) with cardiovascular work as per the guidelines. The
intervention group was evaluated on a 3-week basis. Full evaluation was carried
out at baseline and at 12 weeks. RESULTS: Forty patients were randomized to the
intervention with 38 controls. In the exercise intervention group, there was a
statistically significant improvement in HAQ (p = 0.00), pain (p = 0.05),
stiffness (p = 0.05), sleep quality (p = 0.04), and fatigue (p = 0.04). In our
control group, there was a statistically significant improvement demonstrated in
their overall perceptions of the benefits of exercise, but none of the other
variables. CONCLUSION: Our study demonstrates that an exercise program resulted
in significant improvement in sleep quality and fatigue. This is particularly
interesting given the importance of fatigue as an outcome measure in RA and gives
us yet another reason to prescribe exercise in this population.
PMID- 25128511
TI - MicroRNA profiling in Chinese patients with primary Sjogren syndrome reveals
elevated miRNA-181a in peripheral blood mononuclear cells.
AB - OBJECTIVE: Characterized by chronic inflammation, dysfunction of exocrine glands,
and systemic autoimmunity, primary Sjogren syndrome (pSS) is a common autoimmune
disease in elderly women. Our study was performed to explore the potential
involvement of microRNA (miRNA) in Chinese patients with pSS. METHODS: Using
microarrays, miRNA expression in peripheral blood mononuclear cells (PBMC) was
profiled in 4 female patients with pSS and 3 healthy participants, followed by a
large-scale study of 33 patients and 10 healthy individuals. Compared to the
healthy participants, 202 miRNA were upregulated and 180 were downregulated in
the patients with pSS. To confirm this finding, a set of regulated miRNA was
further examined in a large patient group, using quantitative reverse
transcriptase-PCR assays. RESULTS: MiR-181a was the miRNA that most profoundly
differed between patients with pSS and healthy individuals; however, similar
miRNA-181a expression profiles were found in groups with different disease
phenotypes. Together, these observations suggested that an elevated miRNA-181a
level is a general phenomenon in Chinese patients with pSS. CONCLUSION: In
addition to the elevated miR-181a levels, our study led to the speculation that
elevated miR-181a levels in the PBMC of these patients compromise the maturation
of B cells, enabling them to recognize and attack autoantigens and resulting in
disease phenotypes. In addition to the regulation of human miRNA, many virus
derived miRNA were unexpectedly upregulated in the patients with pSS, suggesting
that viral infection of PBMC plays a role in this disease.
PMID- 25128512
TI - Predictors of incident depression in systemic lupus erythematosus.
AB - OBJECTIVE: Findings from previous studies of predictors of depression among
patients with systemic lupus erythematosus (SLE) have been inconsistent. The aim
of our study was to identify risk factors that preceded incident depression based
on a large, closely followed longitudinal cohort. METHODS: Data regarding 1609
patients with SLE in the Hopkins Lupus Cohort who had no history of depression
prior to cohort entry were analyzed. Demographic variables, SLE manifestations,
laboratory tests, physician's global assessment, Safety of Estrogens in Lupus
Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI),
cumulative organ damage (Systemic Lupus International Collaborating
Clinics/American College of Rheumatology Damage Index), and onset of depression
were recorded at enrollment and each quarterly visit. Rates of incident
depression were calculated overall, and in subgroups defined by demographic and
clinical variables. Adjusted estimates of association were derived using pooled
logistic regression. RESULTS: The incidence of depression was 29.7 episodes per
1000 person-years. In the multivariable analysis, these variables remained as
independent predictors of incident depression: recent SLE diagnosis, non-Asian
ethnicity, disability, cutaneous activity, longitudinal myelitis, and current
prednisone use of 20 mg/day or higher. Global disease activity (SELENA-SLEDAI)
was not a significant predictor after controlling for prednisone use. CONCLUSION:
Depression in SLE is multifactorial. Higher-dose prednisone (>= 20 mg daily) is 1
important independent risk factor. Global disease activity is not a risk factor,
but cutaneous activity and certain types of neurologic activity (myelitis) are
predictive of depression. The independent effect of prednisone provides
clinicians with an additional incentive to avoid and reduce high-dose prednisone
exposure in SLE.
PMID- 25128513
TI - Tocilizumab treatment increases left ventricular ejection fraction and decreases
left ventricular mass index in patients with rheumatoid arthritis without cardiac
symptoms: assessed using 3.0 tesla cardiac magnetic resonance imaging.
AB - OBJECTIVE: The aim of our pilot study was to prospectively evaluate the effect of
inhibiting interleukin 6 on the left ventricular (LV) structure and function in
patients with rheumatoid arthritis (RA) without cardiac symptoms, using cardiac
magnetic resonance (CMR). METHODS: Female patients with RA with active disease
and healthy controls were enrolled. Cardiac symptoms were absent in all subjects.
Tocilizumab (TCZ; 8 mg/kg IV every 4 weeks) was prescribed for patients with RA
with an inadequate clinical response to methotrexate. All subjects underwent
baseline evaluation of LV function and structure measured by CMR. We compared
measures of LV geometry and function between patients with RA and patients
without RA controls at baseline, and changes in the same variables between
baseline and after 52 weeks of treatment among the group with RA. RESULTS: Twenty
women with RA were compared with 20 women without RA of similar mean age. In
patients with RA at baseline, ejection fraction (EF) was significantly lower (
3.7%) and LV mass index (LVMI) significantly higher (+9.2%) compared with
controls. TCZ treatment resulted in a significant decrease in the Simplified
Disease Activity Index (SDAI) after 52 weeks of treatment, paralleling a
significant increase in EF (+8.2%) and a significant decrease in LVMI (-24.4%)
over the same period. The percentage change in LVMI correlated strongly with the
percentage change in SDAI (r = -0.63, p = 0.0028). LV geometry in the group with
RA at baseline showed eccentric hyper-trophy compared with the group without RA,
a condition that normalized after TCZ treatment. CONCLUSION: TCZ treatment
significantly increased EF and decreased LVMI associated with disease activity.
PMID- 25128514
TI - Responsiveness of magnetic resonance imaging-derived measures over 2.7 years.
AB - OBJECTIVE: To compare the responsiveness of magnetic resonance imaging (MRI)
derived measures of knee osteoarthritis over 2.7 years. METHODS: There were 430
community-based participants (mean age 63.0 yrs, range 51-79 yrs; 51% female)
measured at baseline and 2.7 years later. MRI of the right knee at both
timepoints was performed to assess cartilage volume, cartilage defects, bone
marrow lesions (BML), meniscal pathology, and tibial bone area. Global
measurements were calculated as the sum of tibial and femoral measures.
Standardized response mean (SRM) was calculated as the mean of change divided by
the SD of change. RESULTS: Global tibiofemoral cartilage volume and cartilage
defects had the best SRM of -0.80 and 0.62, respectively. Site-specific
measurements were lower (SRM range for cartilage volume -0.48 to -0.54 and
cartilage defects 0.33 to 0.49). The SRM for BML was 0.12, meniscal pathology
0.39, and tibial bone area -0.09. Cartilage volume and/or defects tended to be
more responsive in those with knee pain, those who were obese, those who were
older, and those with radiographic osteoarthritis. CONCLUSION: Global cartilage
volume demonstrated the best sensitivity to change, suggesting that if we relied
solely on SRM to optimize clinical trial design, then cartilage volume would be
the best outcome measure. However, clinical trials have shown that cartilage
volume may be less responsive to treatment compared to other measures that have
lower SRM (such as BML). Therefore, although one can optimize trial efficiency by
finding more responsive endpoints, both sensitivity to change and magnitude of
benefit should be considered.
PMID- 25128515
TI - Reduced ovarian reserve in patients with Takayasu arteritis.
AB - OBJECTIVE: To assess ovarian reserve markers in patients with Takayasu arteritis
(TA). METHODS: Twenty patients with TA and 24 healthy controls were evaluated for
ovarian reserve by follicle-stimulating hormone, luteinizing hormone, and
estradiol, and antral follicle count (AFC). Anti-Mullerian hormone (AMH) was
measured by ELISA using 2 different kits. Demographical data, menstrual
abnormalities, disease variables, and treatment were also analyzed. RESULTS: The
median current age was similar in patients with TA and controls (31.2 +/- 6.1 vs
30.4 +/- 6.9 yrs, p = 0.69). The frequencies of decreased levels of AMH in
patients with TA were identical using both kits and higher when compared to
controls (50% vs 17%, p = 0.02; 50% vs 19%, p = 0.048). A positive correlation
was observed between the 2 kits in patients with TA (r = +0.93, p < 0.0001) and
in healthy controls (r = +0.93, p < 0.0001). The apparent lower AFC (11 vs 16, p
= 0.13) and the higher frequency of low AFC (41% vs 22%, p = 0.29) in TA compared
to controls did not reach statistical significance. Other hormones were similar
in both groups (p > 0.05). Further evaluation of patients with TA with low AMH
levels (< 1.0 ng/ml) versus normal AMH levels (> 1.0 ng/ml) revealed that the
frequency of current disease activity (p = 1.0) and the median of erythrocyte
sedimentation rate (p = 0.6), C-reactive protein (p = 0.4), prednisone cumulative
dose (p = 0.8), and methotrexate cumulative dose (p = 0.8) were comparable in
both groups. Cyclophosphamide use was reported in only 1 patient with reduced
ovarian reserve, whereas none of the remaining patients received gonadotoxic
drugs. CONCLUSION: To the best of our knowledge, our present study was the first
to suggest that patients with TA may have diminished ovarian reserve.
PMID- 25128516
TI - Persistence and dose escalation of tumor necrosis factor inhibitors in US
veterans with rheumatoid arthritis.
AB - OBJECTIVE: Limited evidence exists comparing the persistence, effectiveness, and
costs of biologic therapies for rheumatoid arthritis in clinical practice.
Comparative effectiveness studies are needed to understand real-world experience
with these agents. We evaluated treatment patterns, costs, and effectiveness of
tumor necrosis factor inhibitor (TNFi) agents in patients enrolled in the
Veterans Affairs Rheumatoid Arthritis (VARA) registry. METHODS: Observational
data from the VARA registry and linked administrative databases were analyzed.
Longitudinal data from VARA patients initiating adalimumab (ADA), etanercept
(ETN), or infliximab (IFX) from 2003 (the date all agents were available within
the Veteran Affairs) to 2010 were analyzed. Outcomes included Disease Activity
Score using 28 joints (DAS28), treatment persistence, dose escalation, and direct
costs of drugs and drug administration. RESULTS: For 563 eligible patients,
baseline DAS28, DAS28 improvements, and persistence on initial treatment were
similar across agents. Fewer patients receiving ETN (n = 5/290; 2%) underwent
dose escalation than did patients taking ADA (n = 32/204; 16%) or IFX (n = 44/69;
64%). Annual costs for first course of TNFi therapy were lower for injectable ADA
($13,100 US) and ETN ($13,500 US) than for intravenously administered IFX
($16,900 US). CONCLUSION: Despite similar persistence and clinical disease
activity for these TNFi agents, rates of dose escalation were highest with ADA
and IFX. Higher overall costs were noted for IFX without increases in
effectiveness.
PMID- 25128517
TI - Mortality, recurrence, and hospital course of patients with systemic sclerosis
related acute intestinal pseudo-obstruction.
AB - OBJECTIVE: Acute intestinal pseudo-obstruction is a rare gastrointestinal
manifestation of systemic sclerosis (SSc) with few data existing as to its
demographics, clinical course, outcomes, and mortality. METHODS: We undertook a
case-control study to describe 64 cases in 37 unique patients, of whom 70% had
spontaneous resolution with conservative measures of intravenous hydration and
bowel rest, 9% underwent surgical resection, and 25% required prolonged total
parenteral nutrition (TPN). RESULTS: Hospital course was for a mean of 12 +/-
12.5 days and there was a 16% patient mortality in our population. In a subgroup
analysis, patients who had recurrent episodes of pseudo-obstruction were less
likely to have esophageal involvement from SSc, and more likely to need prolonged
TPN. Mortality tended to be higher in male patients and patients who did not have
SSc-related esophageal involvement, and also in patients who had low hemoglobin
and serum albumin at presentation. The need for a nasogastric tube for
decompression and a surgical intervention correlated with a more prolonged
hospital stay. CONCLUSION: To the best of our knowledge, ours is the largest
study looking at this rare manifestation of SSc.
PMID- 25128518
TI - A multibiomarker disease activity score for rheumatoid arthritis predicts
radiographic joint damage in the BeSt study.
AB - OBJECTIVE: To determine whether a multibiomarker disease activity (MBDA) score
predicts radiographic damage progression in the subsequent year in patients with
early rheumatoid arthritis. METHODS: There were 180 serum samples available in
the BeSt study (trial numbers NTR262, NTR 265): 91 at baseline (84 with
radiographs available) and 89 at 1-year followup (81 with radiographs available).
Radiographs were assessed using the Sharp/van der Heijde Score (SvdH). Twelve
serum biomarkers were measured to determine MBDA scores using a validated
algorithm. Receiver-operating curves and Poisson regression analyses were
performed, with Disease Activity Score (DAS) and MBDA score as independent
variables, and radiographic progression as dependent variable. RESULTS: At
baseline, MBDA scores discriminated more between patients who developed
radiographic progression (increase in SvdH>=5 points) and patients who did not
[area under the curve (AUC) 0.767, 95% CI 0.639-0.896] than did DAS (AUC 0.521,
95% CI 0.358-0.684). At 1 year, MBDA score had an AUC of 0.691 (95% CI 0.453
0.929) and DAS had an AUC of 0.649 (95% CI 0.417-0.880). Adjusted for
anticitrullinated protein antibody status and DAS, higher MBDA scores were
associated with an increased risk for SvdH progression [relative risk (RR) 1.039,
95% CI 1.018-1.059 for baseline MBDA score; 1.037, 95% CI 1.009-1.065 for Year 1
MBDA score]. Categorized high MBDA scores were also correlated with SvdH
progression (RR for high MBDA score at baseline 3.7; low or moderate MBDA score
as reference). At 1 year, high MBDA score gave a RR of 4.6 compared to low MBDA
score. CONCLUSION: MBDA scores predict radiographic damage progression at
baseline and during disease course.
PMID- 25128519
TI - Tubular urate transporter gene polymorphisms differentiate patients with gout who
have normal and decreased urinary uric acid excretion.
AB - OBJECTIVE: Primary gout has been associated with single-nucleotide polymorphisms
(SNP) in several tubular urate transporter genes. No study has assessed the
association of reabsorption and secretion urate transporter gene SNP with gout in
a single cohort of documented primary patients with gout carefully subclassified
as normoexcretors or underexcretors. METHODS: Three reabsorption SNP
(SLC22A12/URAT1, SLC2A9/GLUT9, and SLC22A11/OAT4) and 2 secretion transporter SNP
(SLC17A1/NPT1 and ABCG2/BRCP) were studied in 104 patients with primary gout and
in 300 control subjects. The patients were subclassified into normoexcretors and
underexcretors according to their serum and 24-h urinary uric acid levels under
strict conditions of dietary control. RESULTS: Compared with control subjects,
patients with gout showed different allele distributions of the 5 SNP analyzed.
However, the diagnosis of underexcretor was only positively associated with the
presence of the T allele of URAT1 rs11231825, the G allele of GLUT9 rs16890979,
and the A allele of ABCG2 rs2231142. The association of the A allele of ABCG2
rs2231142 in normoexcretors was 10 times higher than in underexcretors. The C
allele of NPT1 rs1165196 was only significantly associated with gout in patients
with normal uric acid excretion. CONCLUSION: Gout with uric acid underexcretion
is associated with transporter gene SNP related mainly to tubular reabsorption,
whereas uric acid normoexcretion is associated only with tubular secretion SNP.
This finding supports the concept of distinctive mechanisms to account for
hyperuricemia in patients with gout with reduced or normal uric acid excretion.
PMID- 25128520
TI - When to adjust therapy in patients with rheumatoid arthritis after initiation of
etanercept plus methotrexate or methotrexate alone: findings from a randomized
study (COMET).
AB - OBJECTIVE: The objective of these posthoc analyses was to evaluate short-term
clinical outcomes as predictors of poor response after 1 year of treatment with
combination etanercept/methotrexate (ETN/MTX) therapy versus MTX monotherapy in
patients with early rheumatoid arthritis (RA). METHODS: Participants with
moderate to severe RA [28-joint Disease Activity Score-Erythrocyte Sedimentation
Rate (DAS28-ESR) >= 3.2] of 3-24 months' duration received ETN 50 mg weekly plus
MTX or MTX monotherapy for 52 weeks. Regression analyses were performed to
evaluate the likelihood of remission (DAS28-ESR < 2.6) after 1 year despite poor
clinical short-term treatment effects (e.g., absolute or changes from baseline in
DAS28-ESR after 4, 8, 12, 20, and 24 weeks of therapy). RESULTS: The magnitude of
disease activity and its improvement and timing influenced remission probability
in both treatment groups; remission rate was diminished with higher disease
activity levels and lower response levels over time from weeks 4 to 24. The rate
of DAS28-ESR remission at 1 year was generally greater with ETN/MTX than with MTX
alone at most timepoints from weeks 4 to 24. Despite persistent high disease
activity (DAS28-ESR > 5.1) after 4, 8, 12, and 24 weeks of therapy, 35%, 27%,
25%, and 22% of patients, respectively, in the ETN/MTX group achieved DAS28-ESR
remission after 1 year of continuous treatment; the respective proportions were
33%, 27%, 8%, and 13% in the MTX group. CONCLUSION: High disease activity and
less improvement with treatment over time in the initial 24 weeks of treatment,
particularly after 12 weeks, were predictive of a lower remission rate after 1
year.
PMID- 25128521
TI - Cigarette smoke-induced iBALT mediates macrophage activation in a B cell
dependent manner in COPD.
AB - Chronic obstructive pulmonary disease (COPD) is characterized by a progressive
decline in lung function, caused by exposure to exogenous particles, mainly
cigarette smoke (CS). COPD is initiated and perpetuated by an abnormal CS-induced
inflammatory response of the lungs, involving both innate and adaptive immunity.
Specifically, B cells organized in iBALT structures and macrophages accumulate in
the lungs and contribute to CS-induced emphysema, but the mechanisms thereof
remain unclear. Here, we demonstrate that B cell-deficient mice are significantly
protected against CS-induced emphysema. Chronic CS exposure led to an increased
size and number of iBALT structures, and increased lung compliance and mean
linear chord length in wild-type (WT) but not in B cell-deficient mice. The
increased accumulation of lung resident macrophages around iBALT and in
emphysematous alveolar areas in CS-exposed WT mice coincided with upregulated
MMP12 expression. In vitro coculture experiments using B cells and macrophages
demonstrated that B cell-derived IL-10 drives macrophage activation and MMP12
upregulation, which could be inhibited by an anti-IL-10 antibody. In summary, B
cell function in iBALT formation seems necessary for macrophage activation and
tissue destruction in CS-induced emphysema and possibly provides a new target for
therapeutic intervention in COPD.
PMID- 25128522
TI - PKG-1alpha leucine zipper domain defect increases pulmonary vascular tone:
implications in hypoxic pulmonary hypertension.
AB - Pulmonary hypertension (PH) is a chronic disease characterized by a progressive
increase in vasomotor tone, narrowing of the vasculature with structural
remodeling, and increase in pulmonary vascular resistance. Current treatment
strategies include nitric oxide therapy and methods to increase cGMP-mediated
vasodilatation. cGMP-dependent protein kinases (PKG) are known mediators of
nitric oxide- and cGMP-induced vasodilatation. Deletion of PKG-1 in mice has been
shown to induce PH, however, the exact mechanisms by which loss of PKG-1 function
leads to PH is not known. In a mouse model with a selective mutation in the NH2
terminus leucine zipper protein interaction domain of PKG-1alpha [leucine zipper
mutant (LZM)], we found a progressive increase in right ventricular systolic
pressure and right heart hypertrophy compared with wild-type (WT) mice and
increased RhoA-GTPase activity in the lungs. When exposed to chronic hypoxia, LZM
mice developed modestly enhanced right ventricular remodeling compared with WT
mice. Tadalafil, a phosphodiesterase-5 inhibitor that increases cGMP levels,
significantly attenuated hypoxia-induced cardiopulmonary remodeling in WT mice
but had no effect in LZM mice. We conclude that a functional leucine zipper
domain in PKG-1alpha is essential for maintenance of a low pulmonary vascular
tone in normoxia and for cGMP-mediated beneficial effects of phosphodiesterase-5
inhibition in hypoxic cardiopulmonary remodeling.
PMID- 25128523
TI - Real-time monitoring of endogenous lipid peroxidation by exhaled ethylene in
patients undergoing cardiac surgery.
AB - Pulmonary and systemic organ injury produced by oxidative stress including lipid
peroxidation is a fundamental tenet of ischemia-reperfusion injury, inflammatory
response to cardiac surgery, and cardiopulmonary bypass (CPB) but is not
routinely measured in a surgically relevant time frame. To initiate a paradigm
shift toward noninvasive and real-time monitoring of endogenous lipid
peroxidation, we have explored pulmonary excretion and dynamism of exhaled breath
ethylene during cardiac surgery to test the hypothesis that surgical technique
and ischemia-reperfusion triggers lipid peroxidation. We have employed laser
photoacoustic spectroscopy to measure real-time trace concentrations of ethylene
from the patient breath and from the CPB machine. Patients undergoing aortic or
mitral valve surgery-requiring CPB (n = 15) or off-pump coronary artery bypass
surgery (OPCAB) (n = 7) were studied. Skin and tissue incision by diathermy
caused striking (> 30-fold) increases in exhaled ethylene resulting in elevated
levels until CPB. Gaseous ethylene in the CPB circuit was raised upon the
establishment of CPB (> 10-fold) and decreased over time. Reperfusion of
myocardium and lungs did not appear to enhance ethylene levels significantly.
During OPCAB surgery, we have observed increased ethylene in 16 of 30 documented
reperfusion events associated with coronary and aortic anastomoses. Therefore,
novel real-time monitoring of endogenous lipid peroxidation in the intraoperative
setting provides unparalleled detail of endogenous and surgery-triggered
production of ethylene. Diathermy and unprotected regional myocardial ischemia
and reperfusion are the most significant contributors to increased ethylene.
PMID- 25128524
TI - Role of hypoxia-induced transglutaminase 2 in pulmonary artery smooth muscle cell
proliferation.
AB - We previously reported that transglutaminase 2 (TG2) activity is markedly
elevated in lungs of hypoxia-exposed rodent models of pulmonary hypertension
(PH). Since vascular remodeling of pulmonary artery smooth muscle cells (PASMCs)
is important in PH, we undertook the present study to determine whether TG2
activity is altered in PASMCs with exposure to hypoxia and whether that
alteration participates in their proliferative response to hypoxia. Cultured
distal bovine (b) and proximal human (h) PASMCs were exposed to hypoxia (3% O2)
or normoxia (21% O2). mRNA and protein expression were determined by PCR and
Western blot analyses. TG2 activity and function were visualized and determined
by fluorescent labeled 5-pentylamine biotin incorporation and immunoblotting of
serotonylated fibronectin. Cell proliferation was assessed by [(3)H]thymidine
incorporation assay. At 24 h, both TG2 expression and activity were stimulated by
hypoxia in bPASMCs. Activation of TG2 by hypoxia was blocked by inhibition of the
extracellular calcium-sensing receptor or the transient receptor potential
channel V4. In contrast, TG2 expression was blocked by inhibition of the
transcription factor hypoxia-inducible factor-1alpha, supporting the presence of
separate mechanisms for stimulation of activity and expression of TG2. Pulmonary
arterial hypertension patient-derived hPASMCs were found to proliferate
significantly more rapidly and respond to hypoxia more strongly than control
derived hPASMCs. Similar to bovine cells, hypoxia-induced proliferation of
patient-derived cells was blocked by inhibition of TG2 activity. Our results
suggest an important role for TG2, mediated by intracellular calcium fluxes and
HIF-1alpha, in hypoxia-induced PASMC proliferation and possibly in vascular
remodeling in PH.
PMID- 25128525
TI - Genetic interactions between planar cell polarity genes cause diverse neural tube
defects in mice.
AB - Neural tube defects (NTDs) are among the commonest and most severe forms of
developmental defect, characterized by disruption of the early embryonic events
of central nervous system formation. NTDs have long been known to exhibit a
strong genetic dependence, yet the identity of the genetic determinants remains
largely undiscovered. Initiation of neural tube closure is disrupted in mice
homozygous for mutations in planar cell polarity (PCP) pathway genes, providing a
strong link between NTDs and PCP signaling. Recently, missense gene variants have
been identified in PCP genes in humans with NTDs, although the range of
phenotypes is greater than in the mouse mutants. In addition, the sequence
variants detected in affected humans are heterozygous, and can often be detected
in unaffected individuals. It has been suggested that interactions between
multiple heterozygous gene mutations cause the NTDs in humans. To determine the
phenotypes produced in double heterozygotes, we bred mice with all three pairwise
combinations of Vangl2(Lp), Scrib(Crc) and Celsr1(Crsh) mutations, the most
intensively studied PCP mutants. The majority of double-mutant embryos had open
NTDs, with the range of phenotypes including anencephaly and spina bifida,
therefore reflecting the defects observed in humans. Strikingly, even on a
uniform genetic background, variability in the penetrance and severity of the
mutant phenotypes was observed between the different double-heterozygote
combinations. Phenotypically, Celsr1(Crsh);Vangl2(Lp);Scrib(Crc) triply
heterozygous mutants were no more severe than doubly heterozygous or singly
homozygous mutants. We propose that some of the variation between double-mutant
phenotypes could be attributed to the nature of the protein disruption in each
allele: whereas Scrib(Crc) is a null mutant and produces no Scrib protein,
Celsr1(Crsh) and Vangl2(Lp) homozygotes both express mutant proteins, consistent
with dominant effects. The variable outcomes of these genetic interactions are of
direct relevance to human patients and emphasize the importance of performing
comprehensive genetic screens in humans.
PMID- 25128527
TI - Subdomain II of alpha-isopropylmalate synthase is essential for activity:
inferring a mechanism of feedback inhibition.
AB - The committed step of leucine biosynthesis, converting acetyl-CoA and alpha
ketoisovalerate into alpha-isopropylmalate, is catalyzed by alpha-isopropylmalate
synthase (IPMS), an allosteric enzyme subjected to feedback inhibition by the end
product L-leucine. We characterized the short form IPMS from Leptospira biflexa
(LbIPMS2), which exhibits a catalytic activity comparable with that of the long
form IPMS (LbIPMS1) and has a similar N-terminal domain followed by subdomain I
and subdomain II but lacks the whole C-terminal regulatory domain. We found that
partial deletion of the regulatory domain of LbIPMS1 resulted in a loss of about
50% of the catalytic activity; however, when the regulatory domain was deleted up
to Arg-385, producing a protein that is almost equivalent to the intact LbIPMS2,
about 90% of the activity was maintained. Moreover, in LbIPMS2 or LbIPMS1,
further deletion of several residues from the C terminus of subdomain II
significantly impaired or completely abolished the catalytic activity,
respectively. These results define a complete and independently functional
catalytic module of IPMS consisting of both the N-terminal domain and the two
subdomains. Structural comparison of LbIPMS2 and the Mycobacterium tuberculosis
IPMS revealed two different conformations of subdomain II that likely represent
two substrate-binding states related to cooperative catalysis. The biochemical
and structural analyses together with the previously published hydrogen-deuterium
exchange data led us to propose a conformation transition mechanism for feedback
inhibition mediated by subdomains I and II that might associated with alteration
of the binding affinity toward acetyl-CoA.
PMID- 25128526
TI - Cytoplasmic retention of protein phosphatase 2A inhibitor 2 (I2PP2A) induces
Alzheimer-like abnormal hyperphosphorylation of Tau.
AB - Abnormal hyperphosphorylation of Tau leads to the formation of neurofibrillary
tangles, a hallmark of Alzheimer disease (AD), and related tauopathies. The
phosphorylation of Tau is regulated by protein phosphatase 2A (PP2A), which in
turn is modulated by endogenous inhibitor 2 (I2 (PP2A)). In AD brain, I2 (PP2A)
is translocated from neuronal nucleus to cytoplasm, where it inhibits PP2A
activity and promotes abnormal phosphorylation of Tau. Here we describe the
identification of a potential nuclear localization signal (NLS) in the C-terminal
region of I2 (PP2A) containing a conserved basic motif, (179)RKR(181), which is
sufficient for directing its nuclear localization. The current study further
presents an inducible cell model (Tet-Off system) of AD-type abnormal
hyperphosphorylation of Tau by expressing I2 (PP2A) in which the NLS was
inactivated by (179)RKR(181) -> AAA along with (168)KR(169) -> AA mutations. In
this model, the mutant NLS (mNLS)-I2 (PP2A) (I2 (PP2A)AA-AAA) was retained in the
cell cytoplasm, where it physically interacted with PP2A and inhibited its
activity. Inhibition of PP2A was associated with the abnormal
hyperphosphorylation of Tau, which resulted in microtubule network instability
and neurite outgrowth impairment. Expression of mNLS-I2 (PP2A) activated CAMKII
and GSK-3beta, which are Tau kinases regulated by PP2A. The immunoprecipitation
experiments showed the direct interaction of I2 (PP2A) with PP2A and GSK-3beta
but not with CAMKII. Thus, the cell model provides insights into the nature of
the potential NLS and the mechanistic relationship between I2 (PP2A)-induced
inhibition of PP2A and hyperphosphorylation of Tau that can be utilized to
develop drugs preventing Tau pathology.
PMID- 25128528
TI - Structural and mechanistic insight into the Listeria monocytogenes two-enzyme
lipoteichoic acid synthesis system.
AB - Lipoteichoic acid (LTA) is an important cell wall component required for proper
cell growth in many Gram-positive bacteria. In Listeria monocytogenes, two
enzymes are required for the synthesis of this polyglycerolphosphate polymer. The
LTA primase LtaP(Lm) initiates LTA synthesis by transferring the first
glycerolphosphate (GroP) subunit onto the glycolipid anchor and the LTA synthase
LtaS(Lm) extends the polymer by the repeated addition of GroP subunits to the tip
of the growing chain. Here, we present the crystal structures of the enzymatic
domains of LtaP(Lm) and LtaS(Lm). Although the enzymes share the same fold,
substantial differences in the cavity of the catalytic site and surface charge
distribution contribute to enzyme specialization. The eLtaS(Lm) structure was
also determined in complex with GroP revealing a second GroP binding site.
Mutational analysis confirmed an essential function for this binding site and
allowed us to propose a model for the binding of the growing chain.
PMID- 25128529
TI - Dual role of the Trps1 transcription factor in dentin mineralization.
AB - TRPS1 (tricho-rhino-phalangeal syndrome) is a unique GATA-type transcription
factor that acts as a transcriptional repressor. TRPS1 deficiency and
dysregulated TRPS1 expression result in skeletal and dental abnormalities
implicating TRPS1 in endochondral bone formation and tooth development. Moreover,
patients with tricho-rhino-phalangeal syndrome frequently present with low bone
mass indicating TRPS1 involvement in bone homeostasis. In addition, our previous
data demonstrated accelerated mineralization of the perichondrium in Trps1 mutant
mice and impaired dentin mineralization in Col1a1-Trps1 transgenic mice,
implicating Trps1 in the mineralization process. To understand the role of Trps1
in the differentiation and function of cells producing mineralized matrix, we
used a preodontoblastic cell line as a model of dentin mineralization. We
generated both Trps1-deficient and Trps1-overexpressing stable cell lines and
analyzed the progression of mineralization by alkaline phosphatase and alizarin
red staining. As predicted, based on our previous in vivo data, delayed and
decreased mineralization of Trps1-overexpressing odontoblastic cells was observed
when compared with control cells. This was associated with down-regulation of
genes regulating phosphate homeostasis. Interestingly, Trps1-deficient cells lost
the ability to mineralize and demonstrated decreased expression of several genes
critical for initiating the mineralization process, including Alpl and Phospho1.
Based on these data, we have concluded that Trps1 serves two critical and context
dependent functions in odontoblast-regulated mineralization as follows: 1) Trps1
is required for odontoblast maturation by supporting expression of genes crucial
for initiating the mineralization process, and 2) Trps1 represses the function of
mature cells and, consequently, restricts the extent of extracellular matrix
mineralization.
PMID- 25128530
TI - Phosphatase CD45 both positively and negatively regulates T cell receptor
phosphorylation in reconstituted membrane protein clusters.
AB - T cell receptor (TCR) phosphorylation requires the kinase Lck and phosphatase
CD45. CD45 activates Lck by dephosphorylating an inhibitory tyrosine of Lck to
relieve autoinhibition. However, CD45 also dephosphorylates the TCR, and the
spatial exclusion of CD45 from TCR clustering in the plasma membrane appears to
attenuate this negative effect of CD45. To further investigate the role of CD45
in signal initiation, we reconstituted membrane TCR clusters in vitro on
supported lipid bilayers. Fluorescence microscopy of single clusters showed that
incorporation of CD45 enhanced phosphorylation of TCR clusters, but only when Lck
co-clustered with TCR. We found that clustered Lck autophosphorylated the
inhibitory tyrosine and thus could be activated by CD45, whereas diffusive Lck
molecules did not. In the TCR-Lck clusters and at low CD45 density, we speculate
that the effect of Lck activation may overcome dephosphorylation of TCR,
resulting in a net positive regulation. The CD45 density in physiological TCR
clusters is also low because of the exclusion of CD45. Thus, we propose that the
spatial organization of TCR/Lck/CD45 in T cell membranes is important not only
for modulating the negative role of CD45 but also for creating conditions in
which CD45 has a positive role in signal initiation.
PMID- 25128531
TI - The crystal structure of the plant small GTPase OsRac1 reveals its mode of
binding to NADPH oxidase.
AB - Rac/Rop proteins are Rho-type small GTPases that act as molecular switches in
plants. Recent studies have identified these proteins as key components in many
major plant signaling pathways, such as innate immunity, pollen tube growth, and
root hair formation. In rice, the Rac/Rop protein OsRac1 plays an important role
in regulating the production of reactive oxygen species (ROS) by the NADPH
oxidase OsRbohB during innate immunity. However, the molecular mechanism by which
OsRac1 regulates OsRbohB remains unknown. Here, we report the crystal structure
of OsRac1 complexed with the non-hydrolyzable GTP analog guanosine 5'-(beta,gamma
imido)triphosphate at 1.9 A resolution; this represents the first active-form
structure of a plant small GTPase. To elucidate the ROS production in rice cells,
structural information was used to design OsRac1 mutants that displayed reduced
binding to OsRbohB. Only mutations in the OsRac1 Switch I region showed
attenuated interactions with OsRbohB in vitro. In particular, Tyr(39) and Asp(45)
substitutions suppressed ROS production in rice cells, indicating that these
residues are critical for interaction with and activation of OsRbohB. Structural
comparison of active-form OsRac1 with AtRop9 in its GDP-bound inactive form
showed a large conformational difference in the vicinity of these residues. Our
results provide new insights into the molecular mechanism of the immune response
through OsRac1 and the various cellular responses associated with plant Rac/Rop
proteins.
PMID- 25128532
TI - Reduced plasminogen binding and delayed activation render gamma'-fibrin more
resistant to lysis than gammaA-fibrin.
AB - Fibrin (Fn) clots formed from gamma'-fibrinogen (gamma'-Fg), a variant with an
elongated gamma-chain, are resistant to lysis when compared with clots formed
from the predominant gammaA-Fg, a finding previously attributed to differences in
clot structure due to delayed thrombin-mediated fibrinopeptide (FP) B release or
impaired cross-linking by factor XIIIa. We investigated whether slower lysis of
gamma'-Fn reflects delayed plasminogen (Pg) binding and/or activation by tissue
plasminogen activator (tPA), reduced plasmin-mediated proteolysis of gamma'-Fn,
and/or altered cross-linking. Clots formed from gamma'-Fg lysed more slowly than
those formed from gammaA-Fg when lysis was initiated with tPA/Pg when FPA and FPB
were both released, but not when lysis was initiated with plasmin, or when only
FPA was released. Pg bound to gamma'-Fn with an association rate constant 22%
lower than that to gammaA-Fn, and the lag time for initiation of Pg activation by
tPA was longer with gamma'-Fn than with gammaA-Fn. Once initiated, however, Pg
activation kinetics were similar. Factor XIIIa had similar effects on clots
formed from both Fg isoforms. Therefore, slower lysis of gamma'-Fn clots reflects
delayed FPB release, which results in delayed binding and activation of Pg. When
clots were formed from Fg mixtures containing more than 20% gamma'-Fg, the upper
limit of the normal level, the delay in lysis was magnified. These data suggest
that circulating levels of gamma'-Fg modulate the susceptibility of clots to
lysis by slowing Pg activation by tPA and provide another example of the intimate
connections between coagulation and fibrinolysis.
PMID- 25128533
TI - A review on human reinstatement studies: an overview and methodological
challenges.
AB - In human research, studies of return of fear (ROF) phenomena, and reinstatement
in particular, began only a decade ago and recently are more widely used, e.g.,
as outcome measures for fear/extinction memory manipulations (e.g.,
reconsolidation). As reinstatement research in humans is still in its infancy,
providing an overview of its stability and boundary conditions and summarizing
methodological challenges is timely to foster fruitful future research. As a
translational endeavor, clarifying the circumstances under which (experimental)
reinstatement occurs may offer a first step toward understanding relapse as a
clinical phenomenon and pave the way for the development of new pharmacological
or behavioral ways to prevent ROF. The current state of research does not yet
allow pinpointing these circumstances in detail and we hope this review will aid
the research field to advance in this direction. As an introduction, we begin
with a synopsis of rodent work on reinstatement and theories that have been
proposed to explain the findings. The review however mainly focuses on
reinstatement in humans. We first describe details and variations of the
experimental setup in reinstatement studies in humans and give a general overview
of results. We continue with a compilation of possible experimental boundary
conditions and end with the role of individual differences and behavioral and/or
pharmacological manipulations. Furthermore, we compile important methodological
and design details on the published studies in humans and end with open research
questions and some important methodological and design recommendations as a guide
for future research.
PMID- 25128535
TI - Impact of conscious intent on chunking during motor learning.
AB - Humans and other mammals learn sequences of movements by splitting them into
smaller "chunks." Such chunks are defined by the faster speed of performance of
groups of movements. The purpose of this report is to determine how conscious
intent to learn impacts chunking, an issue that remains unknown. Here, we studied
80 subjects who either with or without conscious intent learned a motor sequence.
Performance was tested before and up to 1-wk post-training. Chunk formation,
carryover of chunks, and concatenation of chunks into longer chunks, all measures
of motor chunking success, were determined at each time-point. We found that
formation, carryover, and concatenation of chunks were comparable across groups
and did not improve over the training session and subsequent testing times. Thus,
motor learning progressed in the absence of improvements in chunking irrespective
of conscious intent. These data suggest that mechanisms other than chunking
contribute to successful motor learning with and without conscious intent.
PMID- 25128534
TI - A unifying model of the role of the infralimbic cortex in extinction and habits.
AB - The infralimbic prefrontal cortex (IL) has been shown to be critical for the
regulation of flexible behavior, but its precise function remains unclear. This
region has been shown to be critical for the acquisition, consolidation, and
expression of extinction learning, leading many to hypothesize that IL suppresses
behavior as part of a "stop" network. However, this framework is at odds with IL
function in habitual behavior in which the IL has been shown to be required for
the expression and acquisition of ongoing habitual behavior. Here, we will review
the current state of knowledge of IL anatomy and function in behavioral
flexibility and provide a testable framework for a single IL mechanism underlying
its function in both extinction and habit learning.
PMID- 25128536
TI - Retrieval is not necessary to trigger reconsolidation of object recognition
memory in the perirhinal cortex.
AB - Memory retrieval has been considered as requisite to initiate memory
reconsolidation; however, some studies indicate that blocking retrieval does not
prevent memory from undergoing reconsolidation. Since N-methyl-D-aspartate (NMDA)
and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate
receptors in the perirhinal cortex have been involved in object recognition
memory formation, the present study evaluated whether retrieval and
reconsolidation are independent processes by manipulating these glutamate
receptors. The results showed that AMPA receptor antagonist infusions in the
perirhinal cortex blocked retrieval, but did not affect memory reconsolidation,
although NMDA receptor antagonist infusions disrupted reconsolidation even if
retrieval was blocked. Importantly, neither of these antagonists disrupted short
term memory. These data suggest that memory underwent reconsolidation even in the
absence of retrieval.
PMID- 25128538
TI - Exposure of airway smooth muscle cells to cigarette smoke extract.
PMID- 25128539
TI - Response to letter by Dr. Marc Hershenson (exposure of airway smooth muscle cells
to cigarette smoke extract).
PMID- 25128544
TI - Ion chromatography for the precise analysis of chloride and sodium in sweat for
the diagnosis of cystic fibrosis.
AB - BACKGROUND: Measurement of chloride in sweat is an essential part of the
diagnostic algorithm for cystic fibrosis. The lack in sensitivity and
reproducibility of current methods led us to develop an ion chromatography/high
performance liquid chromatography (IC/HPLC) method, suitable for the analysis of
both chloride and sodium in small volumes of sweat. METHODS: Precision, linearity
and limit of detection of an in-house developed IC/HPLC method were established.
Method comparison between the newly developed IC/HPLC method and the traditional
Chlorocounter was performed, and trueness was determined using Passing Bablok
method comparison with external quality assurance material (Royal College of
Pathologists of Australasia). RESULTS: Precision and linearity fulfill criteria
as established by UK guidelines are comparable with inductively coupled plasma
mass spectrometry methods. Passing Bablok analysis demonstrated excellent
correlation between IC/HPLC measurements and external quality assessment target
values, for both chloride and sodium. With a limit of quantitation of 0.95
mmol/L, our method is suitable for the analysis of small amounts of sweat and can
thus be used in combination with the Macroduct collection system. CONCLUSIONS:
Although a chromatographic application results in a somewhat more expensive test
compared to a Chlorocounter test, more accurate measurements are achieved. In
addition, simultaneous measurements of sodium concentrations will result in
better detection of false positives, less test repeating and thus faster and more
accurate and effective diagnosis. The described IC/HPLC method, therefore,
provides a precise, relatively cheap and easy-to-handle application for the
analysis of both chloride and sodium in sweat.
PMID- 25128545
TI - David W. Talmage, M.D. (AAI '54) 1919-2014.
PMID- 25128537
TI - 17beta-Estradiol regulates histone alterations associated with memory
consolidation and increases Bdnf promoter acetylation in middle-aged female mice.
AB - Histone acetylation is essential for hippocampal memory formation in young adult
rodents. Although dysfunctional histone acetylation has been associated with age
related memory decline in male rodents, little is known about whether histone
acetylation is altered by aging in female rodents. In young female mice, the
ability of 17beta-estradiol (E2) to enhance object recognition memory
consolidation requires histone H3 acetylation in the dorsal hippocampus. However,
the extent to which histone acetylation is regulated by E2 in middle-aged females
is unknown. The mnemonic benefits of E2 in aging females appear to be greatest in
middle age, and so pinpointing the molecular mechanisms through which E2 enhances
memory at this age could lead to the development of safer and more effective
treatments for maintaining memory function without the side effects of current
therapies. Here, we show that dorsal hippocampal infusion of E2 rapidly enhanced
object recognition and spatial memory, and increased histone H3 acetylation in
the dorsal hippocampus, while also significantly reducing levels of histone
deacetylase (HDAC2 and HDAC3) proteins. E2 specifically increased histone H3
acetylation at Bdnf promoters pII and pIV in the dorsal hippocampus of both young
and middle-aged mice, despite age-related decreases in pI and pIV acetylation.
Furthermore, levels of mature BDNF and pro-BDNF proteins in the dorsal
hippocampus were increased by E2 in middle-aged females. Together, these data
suggest that the middle-aged female dorsal hippocampus remains epigenetically
responsive to E2, and that E2 may enhance memory in middle-aged females via
epigenetic regulation of Bdnf.
PMID- 25128546
TI - Comment on "aneurysmal lesions of patients with abdominal aortic aneurysm contain
clonally expanded T cells".
PMID- 25128547
TI - Response to comment on "aneurysmal lesions of patients with abdominal aortic
aneurysm contain clonally expanded T cells".
PMID- 25128548
TI - Just the FACS.
PMID- 25128549
TI - Pillars article: cell sorting: automated separation of Mammalian cells as a
function of intracellular fluorescence. Science. 1969. 166: 747-749.
PMID- 25128550
TI - Pillars article: demonstration that antigen-binding cells are precursors of
antibody-producing cells after purification with a fluorescence-activated cell
sorter. Proc. Natl. Acad. Sci. 1972. 69: 1934-1938.
PMID- 25128551
TI - Hematopoiesis in steady-state versus stress: self-renewal, lineage fate choice,
and the conversion of danger signals into cytokine signals in hematopoietic stem
cells.
AB - Long-term hematopoietic stem cells (LT-HSCs) replenish the innate and adaptive
immune compartments throughout life. Although significant progress has defined
the major transcription factors that regulate lineage specification, the
architectural proteins that globally coordinate DNA methylation, histone
modification, and changes in gene expression are poorly defined. Provocative new
studies establish the chromatin organizer special AT-rich binding protein 1
(Satb1) as one such global regulator in LT-HSCs. Satb1 is a nuclear organizer
that partitions chromatin through the formation of cage-like structures. By
integrating epigenetic and transcriptional pathways, Satb1 coordinates LT-HSC
division, self-renewal, and lymphoid potential. Unexpected among the assortment
of genes under Satb1 control in hematopoietic stem cells (HSCs) are cytokines, a
finding that takes on additional importance with the provocative finding that
short-term HSCs and downstream multipotent progenitors are potent and
biologically relevant cytokine secretors during stress-mediated hematopoiesis.
Together, these studies reveal a new mechanism of fate regulation and an
unforeseen functional capability of HSCs.
PMID- 25128557
TI - 'The battle for life': Pasteur, anthrax, and the first probiotics.
PMID- 25128552
TI - The multifaceted roles of Bcl11b in thymic and peripheral T cells: impact on
immune diseases.
AB - The transcription factor Bcl11b is expressed in all T cell subsets and
progenitors, starting from the DN2 stage of T cell development, and it regulates
critical processes implicated in the development, function, and survival of many
of these cells. Among the common roles of Bcl11b in T cell progenitors and mature
T cell subsets are the repression of the innate genetic program and, to some
extent, expression maintenance of TCR-signaling components. However, Bcl11b also
has unique roles in specific T cell populations, suggesting that its functions
depend on cell type and activation state of the cell. In this article, we provide
a comprehensive review of the roles of Bcl11b in progenitors, effector T cells,
regulatory T cells, and invariant NKT cells, as well as its impact on immune
diseases. While emphasizing common themes, including some that might be extended
to skin and neurons, we also describe the control of specific functions in
different T cell subsets.
PMID- 25128559
TI - Influence of optic flow on the control of heading and target egocentric direction
during steering toward a goal.
AB - Although previous studies have shown that people use both optic flow and target
egocentric direction to walk or steer toward a goal, it remains in question how
enriching the optic flow field affects the control of heading specified by optic
flow and the control of target egocentric direction during goal-oriented
locomotion. In the current study, we used a control-theoretic approach to
separate the control response specific to these two cues in the visual control of
steering toward a goal. The results showed that the addition of optic flow
information (such as foreground motion and global flow) in the display improved
the overall control precision, the amplitude, and the response delay of the
control of heading. The amplitude and the response delay of the control of target
egocentric direction were, however, not affected. The improvement in the control
of heading with enriched optic flow displays was mirrored by an increase in the
accuracy of heading perception. The findings provide direct support for the claim
that people use the heading specified by optic flow as well as target egocentric
direction to walk or steer toward a goal and suggest that the visual system does
not internally weigh these two cues for goal-oriented locomotion control.
PMID- 25128556
TI - Global mass spectrometry and transcriptomics array based drug profiling provides
novel insight into glucosamine induced endoplasmic reticulum stress.
AB - We investigated the molecular effects of glucosamine supplements, a popular and
safe alternative to nonsteroidal anti-inflammatory drugs, for decreasing pain,
inflammation, and maintaining healthy joints. Numerous studies have reported an
array of molecular effects after glucosamine treatment. We questioned whether the
differences in the effects observed in previous studies were associated with the
focus on a specific subproteome or with the use of specific cell lines or
tissues. To address this question, global mass spectrometry- and transcription
array-based glucosamine drug profiling was performed on malignant cell lines from
different stages of lymphocyte development. We combined global label-free MS
based protein quantitation with an open search for modifications to obtain the
best possible proteome coverage. Our data were largely consistent with previous
studies in a variety of cellular models. We mainly observed glucosamine induced O
GlcNAcylation/O-GalNAcylation (O-HexNAcylation); however, we also observed global
and local changes in acetylation, methylation, and phosphorylation. For example,
our data provides two additional examples of "yin-yang" between phosphorylation
and O-HexNAcylation. Furthermore, we mapped novel O-HexNAc sites on GLU2B and
calnexin. GLU2B and calnexin are known to be located in the endoplasmic reticulum
(ER) and involved in protein folding and quality control. The O-HexNAc sites were
regulated by glucosamine treatment and correlated with the up-regulation of the
ER stress marker GRP78. The occupancy of O-HexNAc on GLU2B and calnexin sites
differed between the cytosolic and nuclear fractions with a higher occupancy in
the cytosolic fraction. Based on our data we propose the hypothesis that O-HexNAc
either inactivates calnexin and/or targets it to the cytosolic fraction. Further,
we hypothesize that O-HexNAcylation induced by glucosamine treatment enhances
protein trafficking.
PMID- 25128561
TI - Tetraspanins at a glance.
AB - Tetraspanins are a family of proteins with four transmembrane domains that play a
role in many aspects of cell biology and physiology; they are also used by
several pathogens for infection and regulate cancer progression. Many
tetraspanins associate specifically and directly with a limited number of
proteins, and also with other tetraspanins, thereby generating a hierarchical
network of interactions. Through these interactions, tetraspanins are believed to
have a role in cell and membrane compartmentalization. In this Cell Science at a
Glance article and the accompanying poster, we describe the basic principles
underlying tetraspanin-based assemblies and highlight examples of how
tetraspanins regulate the trafficking and function of their partner proteins that
are required for the normal development and function of several organs,
including, in humans, the eye, the kidney and the immune system.
PMID- 25128560
TI - Response features across the auditory midbrain reveal an organization consistent
with a dual lemniscal pathway.
AB - The central auditory system has traditionally been divided into lemniscal and
nonlemniscal pathways leading from the midbrain through the thalamus to the
cortex. This view has served as an organizing principle for studying, modeling,
and understanding the encoding of sound within the brain. However, there is
evidence that the lemniscal pathway could be further divided into at least two
subpathways, each potentially coding for sound in different ways. We investigated
whether such an interpretation is supported by the spatial distribution of
response features in the central nucleus of the inferior colliculus (ICC), the
part of the auditory midbrain assigned to the lemniscal pathway. We recorded
responses to pure tone stimuli in the ICC of ketamine-xylazine-anesthetized
guinea pigs and used three-dimensional brain reconstruction techniques to map the
location of the recording sites. Compared with neurons in caudal-and-medial
regions within an isofrequency lamina of the ICC, neurons in rostral-and-lateral
regions responded with shorter first-spike latencies with less spiking jitter,
shorter durations of spiking responses, a higher proportion of spikes occurring
near the onset of the stimulus, lower thresholds, and larger local field
potentials with shorter latencies. Further analysis revealed two distinct
clusters of response features located in either the caudal-and-medial or the
rostral-and-lateral parts of the isofrequency laminae of the ICC. Thus we report
substantial differences in coding properties in two regions of the ICC that are
consistent with the hypothesis that the lemniscal pathway is made up of at least
two distinct subpathways from the midbrain up to the cortex.
PMID- 25128563
TI - Distinct temporal hierarchies in membrane and cytoskeleton dynamics precede the
morphological polarization of developing neurons.
AB - Final morphological polarization of neurons, with the development of a distinct
axon and several dendrites, is preceded by phases where they have a non-polarized
architecture. The earliest of these phases is that of the round neuron arising
from the last mitosis. A second non-polarized stage corresponds to the bipolar
neuron, with two morphologically identical neurites. Both phases have their
distinctive relevance in the establishment of neuronal polarity. During the round
cell stage, a decision is made as to where from the cell periphery a first
neurite will form, thus creating the first sign of asymmetry. At the bipolar
stage a decision is made as to which of the two neurites becomes the axon in
neurons polarizing in vitro, and the leading edge in neurons in situ. In this
study, we analysed cytoskeletal and membrane dynamics in cells at these two 'pre
polarity' stages. By means of time lapse imaging in dissociated hippocampal
neurons and ex vivo cortical slices, we show that both stages are characterized
by polarized intracellular arrangements. However, the stages have distinct
temporal hierarchies: polarized actin dynamics marks the site of first
polarization in round cells, whereas polarized membrane dynamics precedes
asymmetric growth in the bipolar stage.
PMID- 25128562
TI - KIF13B regulates angiogenesis through Golgi to plasma membrane trafficking of
VEGFR2.
AB - Although the trafficking of newly synthesized VEGFR2 to the plasma membrane is a
key determinant of angiogenesis, the molecular mechanisms of Golgi to plasma
membrane trafficking are unknown. Here, we have identified a key role of the
kinesin family plus-end molecular motor KIF13B in delivering VEGFR2 cargo from
the Golgi to the endothelial cell surface. KIF13B is shown to interact directly
with VEGFR2 on microtubules. We also observed that overexpression of truncated
versions of KIF13B containing the binding domains that interact with VEGFR2
inhibited VEGF-induced capillary tube formation. KIF13B depletion prevented VEGF
mediated endothelial migration, capillary tube formation and neo-vascularization
in mice. Impairment in trafficking induced by knockdown of KIF13B shunted VEGFR2
towards the lysosomal degradation pathway. Thus, KIF13B is an essential molecular
motor required for the trafficking of VEGFR2 from the Golgi, and its delivery to
the endothelial cell surface mediates angiogenesis.
PMID- 25128564
TI - The role of mitotic kinases in coupling the centrosome cycle with the assembly of
the mitotic spindle.
AB - The centrosome acts as the major microtubule-organizing center (MTOC) for
cytoskeleton maintenance in interphase and mitotic spindle assembly in vertebrate
cells. It duplicates only once per cell cycle in a highly spatiotemporally
regulated manner. When the cell undergoes mitosis, the duplicated centrosomes
separate to define spindle poles and monitor the assembly of the bipolar mitotic
spindle for accurate chromosome separation and the maintenance of genomic
stability. However, centrosome abnormalities occur frequently and often lead to
monopolar or multipolar spindle formation, which results in chromosome
instability and possibly tumorigenesis. A number of studies have begun to dissect
the role of mitotic kinases, including NIMA-related kinases (Neks), cyclin
dependent kinases (CDKs), Polo-like kinases (Plks) and Aurora kinases, in
regulating centrosome duplication, separation and maturation and subsequent
mitotic spindle assembly during cell cycle progression. In this Commentary, we
review the recent research progress on how these mitotic kinases are coordinated
to couple the centrosome cycle with the cell cycle, thus ensuring bipolar mitotic
spindle fidelity. Understanding this process will help to delineate the
relationship between centrosomal abnormalities and spindle defects.
PMID- 25128566
TI - Quantifying mRNA targeting to P-bodies in living human cells reveals their dual
role in mRNA decay and storage.
AB - The 5'-to-3' mRNA degradation machinery localizes to cytoplasmic processing
bodies (P-bodies), which are non-membranous structures found in all eukaryotes.
Although P-body function has been intensively studied in yeast, less is known
about their role in mammalian cells, such as whether P-body enzymes are actively
engaged in mRNA degradation or whether P-bodies serve as mRNA storage depots,
particularly during cellular stress. We examined the fate of mammalian mRNAs in P
bodies during translational stress, and show that mRNAs accumulate within P
bodies during amino acid starvation. The 5' and 3' ends of the transcripts
residing in P-bodies could be identified, but poly(A) tails were not detected.
Using the MS2 mRNA-tagging system for mRNA visualization in living cells, we
found that a stationary mRNA population formed in P-bodies during translational
stress, which cleared gradually after the stress was relieved. Dcp2-knockdown
experiments showed that there is constant degradation of part of the P-body
associated mRNA population. This analysis demonstrates the dual role of P-bodies
as decay sites and storage areas under regular and stress conditions.
PMID- 25128565
TI - Turning a new page on nucleostemin and self-renewal.
AB - A quintessential trait of stem cells is embedded in their ability to self-renew
without incurring DNA damage as a result of genome replication. One key self
renewal factor is the nucleolar GTP-binding protein nucleostemin (also known as
guanine-nucleotide-binding protein-like 3, GNL3, in invertebrate species).
Several studies have recently pointed to an unexpected role of nucleostemin in
safeguarding the genome integrity of stem and cancer cells. Since its discovery,
the predominant presence of nucleostemin in the nucleolus has led to the notion
that it might function in the card-carrying event of the nucleolus--the
biogenesis of ribosomes. As tantalizing as this might be, a ribosomal role of
nucleostemin is refuted by evidence from recent studies, which argues that
nucleostemin depletion triggers a primary event of DNA damage in S phase cells
that then leads to ribosomal perturbation. Furthermore, there have been
conflicting reports regarding the p53 dependency of nucleostemin activity and the
cell cycle arrest profile of nucleostemin-depleted cells. In this Commentary, I
propose a model that explains how the many contradictory observations surrounding
nucleostemin can be reconciled and suggest that this protein might not be as
multi-tasking as has been previously perceived. The story of nucleostemin
highlights the complexity of the underlying molecular events associated with the
appearance of any cell biological phenotype and also signifies a new
understanding of the genome maintenance program in stem cells.
PMID- 25128567
TI - Histone acetylation in astrocytes suppresses GFAP and stimulates a reorganization
of the intermediate filament network.
AB - Glial fibrillary acidic protein (GFAP) is the main intermediate filament in
astrocytes and is regulated by epigenetic mechanisms during development. We
demonstrate that histone acetylation also controls GFAP expression in mature
astrocytes. Inhibition of histone deacetylases (HDACs) with trichostatin A or
sodium butyrate reduced GFAP expression in primary human astrocytes and
astrocytoma cells. Because splicing occurs co-transcriptionally, we investigated
whether histone acetylation changes the ratio between the canonical isoform
GFAPalpha and the alternative GFAPdelta splice variant. We observed that
decreased transcription of GFAP enhanced alternative isoform expression, as HDAC
inhibition increased the GFAPdelta?GFAPalpha ratio. Expression of GFAPdelta was
dependent on the presence and binding of splicing factors of the SR protein
family. Inhibition of HDAC activity also resulted in aggregation of the GFAP
network, reminiscent of our previous findings of a GFAPdelta-induced network
collapse. Taken together, our data demonstrate that HDAC inhibition results in
changes in transcription, splicing and organization of GFAP. These data imply
that a tight regulation of histone acetylation in astrocytes is essential,
because dysregulation of gene expression causes the aggregation of GFAP, a
hallmark of human diseases like Alexander's disease.
PMID- 25128568
TI - Thyroid hormone and the stunned myocardium.
AB - Acute critically ill patients experience a rapid decline in plasma free thyroid
hormone levels (free triiodothyronine (FT3) and free levothyroxine (FT4)), with a
marked elevation of reverse T3, recognized as the euthyroid sick syndrome (ESS)
or low-T3 syndrome. The ESS is also often associated with depressed myocardial
function, sometimes referred to as the 'stunned myocardium'. Its clinical effects
may vary from minimal hemodynamic impairment to cardiogenic shock. Medical
management may range from aspirin alone to placement of a left ventricular assist
device. With adequate supportive therapy, recovery usually occurs within days or
weeks. The effect of T3/T4 therapy has been studied in three conditions in which
the ESS and myocardial functional depression have been documented - i) transient
regional myocardial ischemia and reperfusion, ii) transient global myocardial
ischemia in patients undergoing cardiac surgery on cardiopulmonary bypass, and
iii) transient inadequate global myocardial perfusion in brain-dead potential
organ donors. Under all three conditions, myocardial ischemia leads to rapid loss
of high-energy phosphates, accumulation of myocardial tissue lactate, and
probably loss of homeostasis of cytosolic calcium, which may further increase
cell injury. There is an inability to generate ATP through the Krebs cycle, which
reduces the high-energy phosphate pool essential for all cell ATPases. Under all
three conditions, following administration of T3/T4, the myocardial dysfunction
was rapidly reversed. We, therefore, cautiously advocate the use of thyroid
hormonal therapy to any patient with the ESS and/or a stunned myocardium.
PMID- 25128569
TI - Local edge statistics provide information regarding occlusion and nonocclusion
edges in natural scenes.
AB - Edges in natural scenes can result from a number of different causes. In this
study, we investigated the statistical differences between edges arising from
occlusions and nonocclusions (reflectance differences, surface change, and cast
shadows). In the first experiment, edges in natural scenes were identified using
the Canny edge detection algorithm. Observers then classified these edges as
either an occlusion edge (one region of an image occluding another) or a
nonocclusion edge. The nonocclusion edges were further subclassified as due to a
reflectance difference, a surface change, or a cast shadow. We found that edges
were equally likely to be classified as occlusion or nonocclusion edges. Of the
nonocclusion edges, approximately 33% were classified as reflectance changes, 9%
as cast shadows, and 58% as surface changes. We also analyzed local statistical
properties like contrast, average edge profile, and slope of the edges. We found
significant differences between the contrast values for each category. Based on
the local contrast statistics, we developed a maximum likelihood classifier to
label occlusion and nonocclusion edges. An 80%-20% cross validation demonstrated
that the human classification could be predicted with 83% accuracy. Overall, our
results suggest that for many edges in natural scenes, there exists local
statistical information regarding the cause of the edge. We believe that this
information can potentially be used by the early visual system to begin the
process of segregating objects from their backgrounds.
PMID- 25128571
TI - Different fixational eye movements mediate the prevention and the reversal of
visual fading.
AB - Fixational eye movements (FEMs; including microsaccades, drift and tremor) are
thought to improve visibility during fixation by thwarting neural adaptation to
unchanging stimuli, but how the different FEM types influence this process is a
matter of debate. Attempts to answer this question have been hampered by the
failure to distinguish between the prevention of fading (where fading is blocked
before it happens in the first place) and the reversal of fading (where vision is
restored after fading has already occurred). Because fading during fixation is a
detriment to clear vision, the prevention of fading, which avoids visual
degradation before it happens, is a more desirable scenario than improving
visibility after fading has occurred. Yet previous studies have not examined the
role of FEMs in the prevention of fading, but have focused on visual restoration
instead. Here we set out to determine the differential contributions and
efficacies of microsaccades and drift to preventing fading in human vision. Our
results indicate that both microsaccades and drift mediate the prevention of
visual fading. We also found that drift is a potentially larger contributor to
preventing fading than microsaccades, although microsaccades are more effective
than drift. Microsaccades moreover prevented foveal and peripheral fading in an
equivalent fashion, and their efficacy was independent of their size, number, and
direction. Our data also suggest that faster drift may prevent fading better than
slower drift. These findings may help to reconcile the long-standing controversy
concerning the comparative roles of microsaccades and drift in visibility during
fixation.
PMID- 25128570
TI - Plasticity in the brainstem vagal circuits controlling gastric motor function
triggered by corticotropin releasing factor.
AB - Stress impairs gastric emptying, reduces stomach compliance and induces early
satiety via vagal actions. We have shown recently that the ability of the anti
stress neuropeptide oxytocin (OXT) to modulate vagal brainstem circuits undergoes
short-term plasticity via alterations in cAMP levels subsequent to vagal afferent
fibre-dependent activation of metabotropic glutamate receptors. The aim of the
present study was to test the hypothesis that the OXT-induced gastric response
undergoes plastic changes in the presence of the prototypical stress hormone,
corticotropin releasing factor (CRF). Whole cell patch clamp recordings showed
that CRF increased inhibitory GABAergic synaptic transmission to identified
corpus-projecting dorsal motor nucleus of the vagus (DMV) neurones. In naive
brainstem slices, OXT perfusion had no effect on inhibitory synaptic
transmission; following exposure to CRF (and recovery from its actions), however,
re-application of OXT inhibited GABAergic transmission in the majority of
neurones tested. This uncovering of the OXT response was antagonized by
pretreatment with protein kinase A or adenylate cyclase inhibitors, H89 and di
deoxyadenosine, respectively, indicating a cAMP-mediated mechanism. In naive
animals, OXT microinjection in the dorsal vagal complex induced a NO-mediated
corpus relaxation. Following CRF pretreatment, however, microinjection of OXT
attenuated or, at times reversed, the gastric relaxation which was insensitive to
l-NAME but was antagonized by pretreatment with a VIP antagonist.
Immunohistochemical analyses of vagal motoneurones showed an increased number of
oxytocin receptors present on GABAergic terminals of CRF-treated or stressed vs.
naive rats. These results indicate that CRF alters vagal inhibitory circuits that
uncover the ability of OXT to modulate GABAergic currents and modifies the
gastric corpus motility response to OXT.
PMID- 25128573
TI - Determination of cable parameters in skeletal muscle fibres during repetitive
firing of action potentials.
AB - Recent studies in rat muscle fibres show that repetitive firing of action
potentials causes changes in fibre resting membrane conductance (Gm) that reflect
regulation of ClC-1 Cl(-) and KATP K(+) ion channels. Methodologically, these
findings were obtained by inserting two microelectrodes at close proximity in the
same fibres enabling measurements of fibre input resistance (Rin) in between
action potential trains. Since the fibre length constant (lambda) could not be
determined, however, the calculation of Gm relied on the assumptions that the
specific cytosolic resistivity (Ri) and muscle fibre volume remained constant
during the repeated action potential firing. Here we present a three
microelectrode technique that enables determinations of multiple cable parameters
in action potential-firing fibres including Rin and lambda as well as waveform
and conduction velocities of fully propagating action potentials. It is shown
that in both rat and mouse extensor digitorum longus (EDL) fibres, action
potential firing leads to substantial changes in both muscle fibre volume and Ri.
The analysis also showed, however, that regardless of these changes, rat and
mouse EDL fibres both exhibited initial decreases in Gm that were eventually
followed by a ~3-fold, fully reversible increase in Gm after the firing of 1450
1800 action potentials. Using this three-electrode method we further show that
the latter rise in Gm was closely associated with excitation failures and loss of
action potential signal above -20 mV.
PMID- 25128575
TI - Catecholamine exocytosis during low frequency stimulation in mouse adrenal
chromaffin cells is primarily asynchronous and controlled by the novel mechanism
of Ca2+ syntilla suppression.
AB - Adrenal chromaffin cells (ACCs), stimulated by the splanchnic nerve, generate
action potentials (APs) at a frequency near 0.5 Hz in the resting physiological
state, at times described as 'rest and digest'. How such low frequency
stimulation in turn elicits sufficient catecholamine exocytosis to set basal
sympathetic tone is not readily explained by the classical mechanism of stimulus
secretion coupling, where exocytosis is synchronized to AP-induced Ca(2+) influx.
By using simulated action potentials (sAPs) at 0.5 Hz in isolated patch-clamped
mouse ACCs, we show here that less than 10% of all catecholaminergic exocytosis,
measured by carbon fibre amperometry, is synchronized to an AP. The asynchronous
phase, the dominant phase, of exocytosis does not require Ca(2+) influx.
Furthermore, increased asynchronous exocytosis is accompanied by an AP-dependent
decrease in frequency of Ca(2+) syntillas (i.e. transient, focal Ca(2+) release
from internal stores) and is ryanodine sensitive. We propose a mechanism of
disinhibition, wherein APs suppress Ca(2+) syntillas, which themselves inhibit
exocytosis as they do in the case of spontaneous catecholaminergic exocytosis.
PMID- 25128574
TI - PGC1-alpha over-expression prevents metabolic alterations and soleus muscle
atrophy in hindlimb unloaded mice.
AB - Prolonged skeletal muscle inactivity causes muscle fibre atrophy. Redox imbalance
has been considered one of the major triggers of skeletal muscle disuse atrophy,
but whether redox imbalance is actually the major cause or simply a consequence
of muscle disuse remains of debate. Here we hypothesized that a metabolic stress
mediated by PGC-1alpha down-regulation plays a major role in disuse atrophy.
First we studied the adaptations of soleus to mice hindlimb unloading (HU) in the
early phase of disuse (3 and 7 days of HU) with and without antioxidant treatment
(trolox). HU caused a reduction in cross-sectional area, redox status alteration
(NRF2, SOD1 and catalase up-regulation), and induction of the ubiquitin
proteasome system (MuRF-1 and atrogin-1 mRNA up-regulation) and autophagy
(Beclin1 and p62 mRNA up-regulation). Trolox completely prevented the induction
of NRF2, SOD1 and catalase mRNAs, but not atrophy or induction of catabolic
systems in unloaded muscles, suggesting that oxidative stress is not a major
cause of disuse atrophy. HU mice showed a marked alteration of oxidative
metabolism. PGC-1alpha and mitochondrial complexes were down-regulated and DRP1
was up-regulated. To define the link between mitochondrial dysfunction and disuse
muscle atrophy we unloaded mice overexpressing PGC-1alpha. Transgenic PGC-1alpha
animals did not show metabolic alteration during unloading, preserving muscle
size through the reduction of autophagy and proteasome degradation. Our results
indicate that mitochondrial dysfunction plays a major role in disuse atrophy and
that compounds inducing PGC-1alpha expression could be useful to treat/prevent
muscle atrophy.
PMID- 25128577
TI - Mentoring practices benefiting pediatric nurses.
AB - Previous studies examining predictors of pediatric nurse protege mentoring
benefits demonstrated that protege perception of quality was the single best
predictor of mentoring benefits. The ability to identify the mentoring practices
that predict specific benefits for individual nurses provides a better
understanding of how mentoring relationships can be leveraged within health care
organizations promoting mutual mentoring benefits. This descriptive
correlational, non-experimental study of nurses at a northeast Ohio, Magnet(r)
recognized, free-standing pediatric hospital advances nursing science by
demonstrating how mentoring practices benefit pediatric nurse proteges.
PMID- 25128576
TI - Activation of TRPC channels contributes to OA-NO2-induced responses in guinea-pig
dorsal root ganglion neurons.
AB - Effects of nitro-oleic acid (OA-NO2) on TRP channels were examined in guinea-pig
dissociated dorsal root ganglia (DRG) neurons using calcium imaging and patch
clamp techniques. OA-NO2 increased intracellular Ca(2+) in 60-80% DRG neurons. 1
Oleoyl-2acetyl-sn-glycerol (OAG), a TRPC agonist, elicited responses in 36% of OA
NO2-sensitive neurons while capsaicin (TRPV1 agonist) or allyl-isothiocyanate
(AITC, TRPA1 agonist) elicited responses in only 16% and 10%, respectively, of
these neurons. A TRPV1 antagonist (diarylpiperazine, 5 MUm) in combination with a
TRPA1 antagonist (HC-030031, 30 MUm) did not change the amplitude of the Ca(2+)
transients or percentage of neurons responding to OA-NO2; however, a reducing
agent DTT (50 mm) or La(3+) (50 MUm) completely abolished OA-NO2 responses. OA
NO2 also induced a transient inward current associated with a membrane
depolarization followed by a prolonged outward current and hyperpolarization in
80% of neurons. The reversal potentials of inward and outward currents were
approximately -20 mV and -60 mV, respectively. Inward current was reduced when
extracellular Na(+) was absent, but unchanged by niflumic acid (100 MUm), a Cl(-)
channel blocker. Outward current was abolished in the absence of extracellular
Ca(2+) or a combination of two Ca(2+)-activated K(+) channel blockers
(iberiotoxin, 100 nm and apamin, 1 MUm). BTP2 (1 or 10 MUm), a broad spectrum
TRPC antagonist, or La(3+) (50 MUm) completely abolished OA-NO2 currents. RT-PCR
performed on mRNA extracted from DRGs revealed the expression of all seven
subtypes of TRPC channels. These results support the hypothesis that OA-NO2
activates TRPC channels other than the TRPV1 and TRPA1 channels already known to
be targets in rat and mouse sensory neurons and challenge the prevailing view
that electrophilic compounds act specifically on TRPA1 or TRPV1 channels. The
modulation of sensory neuron excitability via actions on multiple TRP channels
can contribute to the anti-inflammatory effect of OA-NO2.
PMID- 25128578
TI - Enhanced survival of retinal ganglion cells is mediated by Muller glial cell
derived PEDF.
AB - The death of retinal ganglion cells (RGC) leads to visual impairment and
blindness in ocular neurodegenerative diseases, primarily in glaucoma and
diabetic retinopathy; hence, mechanisms that contribute to protecting RGC from
ischemia/hypoxia are of great interest. We here address the role of retinal glial
(Muller) cells and of pigment-epithelium-derived factor (PEDF), one of the main
neuroprotectants released from the glial cells. We show that the hypoxia-induced
loss in the viability of cultured purified RGC is due to apoptosis, but that the
number of viable RGC increases when co-cultured with Muller glial cells
suggesting that glial soluble mediators attenuate the death of RGC. When PEDF was
ablated from Muller cells a significantly lower number of RGC survived in RGC
Muller cell co-cultures indicating that PEDF is a major survival factor allowing
RGC to escape cell death. We further found that RGC express a PEDF receptor known
as patatin-like phospholipase domain-containing protein 2 (PNPLA2) and that PEDF
exposure, as well as the presence of Muller cells, leads to an activation of
nuclear factor (NF)-kappaB in RGC. Furthermore, adding an NF-kappaB inhibitor
(SN50) to PEDF-treated RGC cultures reduced the survival of RGC. These findings
strongly suggest that NF-kappaB activation in RGC is critically involved in the
pro-survival action of Muller-cell derived PEDF and plays an important role in
maintaining neuronal survival.
PMID- 25128580
TI - Editorial.
PMID- 25128579
TI - Biomechanical strain as a trigger for pore formation in Schlemm's canal
endothelial cells.
AB - The bulk of aqueous humor passing through the conventional outflow pathway must
cross the inner wall endothelium of Schlemm's canal (SC), likely through micron
sized transendothelial pores. SC pore density is reduced in glaucoma, possibly
contributing to obstructed aqueous humor outflow and elevated intraocular
pressure (IOP). Little is known about the mechanisms of pore formation; however,
pores are often observed near dome-like cellular outpouchings known as giant
vacuoles (GVs) where significant biomechanical strain acts on SC cells. We
hypothesize that biomechanical strain triggers pore formation in SC cells. To
test this hypothesis, primary human SC cells were isolated from three non
glaucomatous donors (aged 34, 44 and 68), and seeded on collagen-coated elastic
membranes held within a membrane stretching device. Membranes were then exposed
to 0%, 10% or 20% equibiaxial strain, and the cells were aldehyde-fixed 5 min
after the onset of strain. Each membrane contained 3-4 separate monolayers of SC
cells as replicates (N = 34 total monolayers), and pores were assessed by
scanning electron microscopy in 12 randomly selected regions (~65,000 MUm(2) per
monolayer). Pores were identified and counted by four independent masked
observers. Pore density increased with strain in all three cell lines (p <
0.010), increasing from 87 +/- 36 pores/mm(2) at 0% strain to 342 +/- 71 at 10%
strain; two of the three cell lines showed no additional increase in pore density
beyond 10% strain. Transcellular "I-pores" and paracellular "B-pores" both
increased with strain (p < 0.038), however B-pores represented the majority (76%)
of pores. Pore diameter, in contrast, appeared unaffected by strain (p = 0.25),
having a mean diameter of 0.40 MUm for I-pores (N = 79 pores) and 0.67 MUm for B
pores (N = 350 pores). Pore formation appears to be a mechanosensitive process
that is triggered by biomechanical strain, suggesting that SC cells have the
ability to modulate local pore density and filtration characteristics of the
inner wall endothelium based on local biomechanical cues. The molecular
mechanisms of pore formation and how they become altered in glaucoma may be
studied in vitro using stretched SC cells.
PMID- 25128581
TI - Roles of the two type II NADH dehydrogenases in the survival of Mycobacterium
tuberculosis in vitro.
AB - Most bacteria are able to generate sufficient amounts of ATP from substrate level
phosphorylation, thus rendering the respiratory oxidative phosphorylation non
critical. In mycobacteria, including Mycobacterium tuberculosis, ATP generation
by oxidative phosphorylation is an essential process. Of the two types of NADH
dehydrogenases (type I and type II), the type II NADH dehydrogenase (Ndh) which
is inhibited by phenothiazines has been thought to be essential. In M.
tuberculosis there are two Ndh isozymes (Ndh and NdhA) coded by ndh and ndhA
genes respectively. Ndh and NdhA share a high degree of amino acid similarity.
Both the enzymes have been shown to be enzymatically active and are inhibited by
phenothiazines, suggesting a functional similarity between the two. We attempted
gene knockout of ndh and ndhA genes in wild type and merodiploid backgrounds. It
was found that ndh gene cannot be inactivated in a wild type background, though
it was possible to do so when an additional copy of ndh was provided. This showed
that in spite of its apparent functional equivalence, NdhA cannot complement the
loss of Ndh in M. tuberculosis. We also showed that NdhA is not essential in M.
tuberculosis as the ndhA gene could be deleted in a wild type strain of M.
tuberculosis without causing any adverse effects in vitro. RT-PCR analysis of in
vitro grown M. tuberculosis showed that ndhA gene is actively transcribed. This
study suggests that despite being biochemically similar, Ndh and NdhA play
different roles in the physiology of M. tuberculosis.
PMID- 25128582
TI - Isolation, characterization and expression analysis of the BABY BOOM (BBM) gene
from Larix kaempferi * L. olgensis during adventitious rooting.
AB - The full-length cDNA and genomic sequences of the BABY BOOM (BBM) gene,
designated LkBBM, were isolated from Larix kaempferi * Larix olgensis. The 3324
bp cDNA was cloned and its open reading frame (ORF) consists of 2370 nucleotides.
The deduced 789 amino acid protein contains two AP2 domains and a BBM specific
motif. Four conserved motifs between BBM and PLT were identified, which may be
conducive to the similar function of BBM and PLT. The three dimensional (3D)
structure of LkBBM was predicted and beta-sheets in the AP2-R2 domain of LkBBM
might recognize the specific base pairs in the major groove. Analysis of the
LkBBM gene structure indicates that the gene has eight introns and nine exons. In
the 5'-flanking promoter region of LkBBM, many important potential cis-acting
elements were identified, such as the TATABOX5 element (a functional TATA
element), ROOTMOTIFTAPOX1 element (element of root specificity), AUXREPSIAA4
element (element involved in auxin responsiveness and gene expression in root
meristem), MYB1AT element (element involved in MYB recognition), ARR1AT element
(element involved in cytokinin responsiveness), GARE1OSREP1 element (element
involved in gibberellin responsiveness) and PYRIMIDINEBOXHVEPB1 element (element
involved in abscisic acid responsiveness), which all suggested that the
expression of LkBBM is highly regulated. Compared with gene expression levels in
the stem, stem tip and leaf, LkBBM shows a specific expression in the root, which
indicates that LkBBM plays a key role in regulating the development and growth of
root in larch. In the processing of larch adventitious root formation, LkBBM
started to express on the eighth day after rooting treatment and its transcript
level increased continuously afterwards. According to the gene characteristics,
LkBBM is proposed as a molecular marker for root primordia of larch, and the
initial period of LkBBM expression may be the formation period of root primordia
in the processing of adventitious rooting of larch.
PMID- 25128583
TI - Association of TLR and TREM-1 gene polymorphisms with risk of coronary artery
disease in a Russian population.
AB - Atherosclerosis, manifesting itself as acute coronary syndrome, stroke, and
peripheral arterial diseases, is a chronic progressive inflammatory disease which
is driven by responses of both innate and adaptive immunity. Toll-like receptors
(TLRs) and Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) are
important effectors of the innate immune system, and polymorphisms within genes
encoding them may increase risk of occurrence of various pathologies including
cardiovascular disorders. Thus, we carried out a genetic association study on the
sample of 702 consecutive Caucasian (Russian) patients with coronary artery
disease (CAD) and 300 age-, sex-, and ethnicity-matched healthy controls. We
revealed that the C/C genotype of the TLR1 rs5743551 polymorphism was
significantly associated with a reduced risk of CAD according to the recessive
model (OR=0.41, 95% CI=0.20-0.84, P=0.017, adjusted by age and gender).
Concerning TREM-1 gene polymorphisms, we found that A/A genotype of the rs2234237
polymorphism, the G/G genotype of the rs6910730 polymorphism, the C/C genotype of
the rs9471535 polymorphism, and the T/T genotype of the rs4711668 polymorphism
were significantly associated with elevated CAD risk according to the recessive
model (OR=5.52, 95% CI=1.17-25.98, P=0.011; OR=4.28, 95% CI=1.09-16.81, P=0.021;
OR=5.55, 95% CI=1.18-26.09, P=0.011, and OR=1.66, 95% CI=1.10-2.52, P=0.014,
respectively, adjusted by age and gender). Conversely, the G allele of the
rs1817537 polymorphism, the T allele of the rs2234246 polymorphism, and the T
allele of the rs3804277 polymorphism significantly correlated with similarly
decreased risk of CAD according to the dominant model (OR=0.57, 95% CI=0.40-0.81,
P=0.0013; OR=0.59, 95% CI=0.42-0.84, P=0.003, and OR=0.58, 95% CI=0.41-0.81,
P=0.0014, respectively, adjusted by age and gender). We conclude that certain TLR
and TREM-1 gene polymorphisms may be associated with CAD in Russian population;
however, their significance as predictive and pathogenic markers of CAD should be
interpreted with caution in other populations.
PMID- 25128584
TI - PDE7A1 hydrolyzes cCMP.
AB - The degradation and biological role of the cyclic pyrimidine nucleotide cCMP is
largely elusive. We investigated nucleoside 3',5'-cyclic monophosphate (cNMP)
specificity of six different recombinant phosphodiesterases (PDEs) by using a
highly-sensitive HPLC-MS/MS detection method. PDE7A1 was the only enzyme that
hydrolyzed significant amounts of cCMP. Enzyme kinetic studies using purified GST
tagged truncated PDE7A1 revealed a cCMP KM value of 135 +/- 19 MUM. The Vmax for
cCMP hydrolysis reached 745 +/- 27 nmol/(minmg), which is about 6-fold higher
than the corresponding velocity for adenosine 3',5'-cyclic monophosphate (cAMP)
degradation. In summary, PDE7A is a high-speed and low-affinity PDE for cCMP.
PMID- 25128585
TI - Ins-4 and daf-28 function redundantly to regulate C. elegans L1 arrest.
AB - Caenorhabditis elegans larvae reversibly arrest development in the first larval
stage in response to starvation (L1 arrest or L1 diapause). Insulin-like
signaling is a critical regulator of L1 arrest. However, the C. elegans genome
encodes 40 insulin-like peptides, and it is unknown which peptides participate in
nutritional control of L1 development. Work in other contexts has revealed that
insulin-like genes can promote development ("agonists") or developmental arrest
("antagonists"), suggesting that such agonists promote L1 development in response
to feeding. We measured mRNA expression dynamics with high temporal resolution
for all 40 insulin-like genes during entry into and recovery from L1 arrest.
Nutrient availability influences expression of the majority of insulin-like
genes, with variable dynamics suggesting complex regulation. We identified
thirteen candidate agonists and eight candidate antagonists based on expression
in response to nutrient availability. We selected ten candidate agonists (daf-28,
ins-3, ins-4, ins-5, ins-6, ins-7, ins-9, ins-26, ins-33 and ins-35) for further
characterization in L1 stage larvae. We used destabilized reporter genes to
determine spatial expression patterns. Expression of candidate agonists is
largely overlapping in L1 stage larvae, suggesting a role of the intestine,
chemosensory neurons ASI and ASJ, and the interneuron PVT in control of L1
development. Transcriptional regulation of candidate agonists is most significant
in the intestine, as if internal nutrient status is a more important influence on
transcription than sensory perception. Phenotypic analysis of single and compound
deletion mutants did not reveal effects on L1 developmental dynamics, though
simultaneous disruption of ins-4 and daf-28 increases survival of L1 arrest.
Furthermore, overexpression of ins-4, ins-6 or daf-28 alone decreases survival
and promotes cell division during starvation. These results suggest extensive
functional overlap among insulin-like genes in nutritional control of L1
development while highlighting the role of ins-4, daf-28 and to a lesser extent
ins-6.
PMID- 25128587
TI - The neural correlates of tic inhibition in Gilles de la Tourette syndrome.
AB - Tics in Gilles de la Tourette syndrome (GTS) resemble fragments of normal motor
behaviour but appear in an intrusive, repetitive and context-inappropriate
manner. Although tics can be voluntarily inhibited on demand, the neural
correlates of this process remain unclear. 14 GTS adults without relevant
comorbidities participated in this study. First, tic severity and voluntary tic
inhibitory capacity were evaluated outside the scanner. Second, patients were
examined with resting state functional magnetic resonance imaging (RS-fMRI) in
two states, free ticcing and voluntary tic inhibition. Local synchronization of
spontaneous fMRI-signal was analysed with regional homogeneity (ReHo) and
differences between both states (free ticcing1000 mg L(-1). Inhibition of bioluminescence was generally a more
sensitive endpoint for MTBE toxicity than measuring intracellular ATP levels and
heterotrophic CO2 assimilation. A weak estrogenic response was detected for MTBE
at concentrations ? 3.7 g L(-1) using an estrogen inducible bioluminescent yeast
strain (S. cerevisiae BLYES). Microbial hydrolytic enzyme activity in groundwater
was affected by MTBE with EC10 values of 0.5-787 mg L(-1), and EC50 values of 59
3073 for alkaline phosphatase, arylsulfatase, beta-1,4-glucanase, N-acetyl-beta-d
glucosaminidase, and leucine-aminopeptidase. Microbial alkaline phosphatase and
beta-1,4-glucanase activity were most sensitive to MTBE exposure with EC50 ? 64.8
mg L(-1). The study suggests that bioassays with luminescent A. fischeri, and
fluorescent assays targeting hydrolytic enzyme activity are good candidates for
monitoring microbial MTBE toxicity in contaminated water.
PMID- 25128635
TI - Characteristics of online compulsive buying in Parisian students.
AB - BACKGROUND: Online compulsive buying is a little-studied behavioral disorder.
AIMS: To better understand its clinical aspects by focusing on (i) prevalence
rate, (ii) correlation with other addictions, (iii) influence of means of access,
(iv) motivations to shop to the internet and (v) financial and time-consuming
consequences. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: 200
students in two different centers of Paris Diderot University - Paris VII.
MEASUREMENTS: Brief self-questionnaires, to screen online compulsive buying,
internet addiction, alcohol and tobacco use disorders, to rate frequency of
online purchase by private-sale websites, by advertising banners, by mobile phone
or to avoid stores, to rate motivations like "more discreet", "lonelier", "larger
variety of products", "more immediate positive feelings", and "cheaper" and to
assess the largest amount of online purchasing and the average proportion of
monthly earnings, and time spent, both day and night. FINDINGS: Prevalence of
online compulsive buying was 16.0%, while prevalence of internet addiction was
26.0%. We found no significant relationship with cyberdependence, alcohol or
tobacco use disorders. Online compulsive buyers accessed more often shopping
online by private-sale websites (56.2% vs 30.5%, p<0.0001) or by mobile phone
(22.5% vs 7.9%, p=0.005) and preferred online shopping because of exhaustive
offer (p<0.0001) and immediate positive feelings (p<0.0001). Online compulsive
buyers spent significantly more money and more time in online shopping.
CONCLUSION: Online compulsive buying seems to be a distinctive behavioral
disorder with specific factors of loss of control and motivations, and overall
financial and time-consuming impacts. More research is needed to better
characterize it.
PMID- 25128636
TI - Indirect effects of smoking motives on adolescent anger dysregulation and
smoking.
AB - Cigarette smoking is one of the leading causes of disease and death in the United
States, and smoking typically begins in adolescence. It is therefore important to
understand factors that relate to increased risk for cigarette smoking during
this stage of development. Adolescence is a period when emotion regulatory
capacities are still emerging and a common affective state to be regulated is
anger, which adult research has linked to nicotine use. Drawing from work
suggesting that negative affect reduction motives are one of the most common
reasons for cigarette smoking, the current study was designed to evaluate the
indirect effects of negative affect reduction motives on the relation between
anger dysregulation and nicotine use within a sample of 119 treatment-seeking
adolescents enrolled in group-based residential therapy. Results were generally
consistent with hypotheses, suggesting significant indirect effects of negative
affect reduction smoking motives on the relation between anger dysregulation and
smoking outcomes. Findings are discussed in terms of negative affect reduction
motives for cigarette use in the context of anger regulation among youths.
PMID- 25128637
TI - Technology-based support via telephone or web: a systematic review of the effects
on smoking, alcohol use and gambling.
AB - A systematic review of the literature on telephone or internet-based support for
smoking, alcohol use or gambling was performed. Studies were included if they met
the following criteria: The design being a randomized control trail (RCT),
focused on effects of telephone or web based interventions, focused on pure
telephone or internet-based self-help, provided information on alcohol or tobacco
consumption, or gambling behavior, as an outcome, had a follow-up period of at
least 3months, and included adults. Seventy-four relevant studies were found; 36
addressed the effect of internet interventions on alcohol consumption, 21 on
smoking and 1 on gambling, 12 the effect of helplines on smoking, 2 on alcohol
consumption, and 2 on gambling. Telephone helplines can have an effect on tobacco
smoking, but there is no evidence of the effects for alcohol use or gambling.
There are some positive findings regarding internet-based support for heavy
alcohol use among U.S. college students. However, evidence on the effects of
internet-based support for smoking, alcohol use or gambling are to a large extent
inconsistent.
PMID- 25128639
TI - Mass gathering medicine: 2014 Hajj and Umra preparation as a leading example.
AB - The importation of infectious diseases during a mass gathering may result in
outbreaks. Infectious diseases associated with mass gatherings vary depending on
the type and location of the mass gathering. The annual Hajj to Makkah in Saudi
Arabia is one of the largest annual religious mass gatherings in the world.
Preparation for the Hajj encompasses multiple sectors to develop comprehensive
plans. These plans include risk assessment, utilizing existing medical
infrastructure, developing electronic and paper-based surveillance activity, and
the use of information technology. In this review, we describe key features of
the preparedness for the 2014 Hajj and Umra, review the recent impact of emerging
viruses such as Ebola in West Africa and the Middle East respiratory syndrome
coronavirus (MERS-CoV) in affected countries, and highlight the updated
requirements and the required vaccines.
PMID- 25128638
TI - A comparison of Cambodian-American adolescent substance use behavior to national
and local norms.
AB - INTRODUCTION: This study was designed to compare rates of alcohol, marijuana, and
cigarette use in Cambodian-American adolescents with norms from nationally- and
regionally-representative peers. METHODS: Substance use data from 439 10th grade
Cambodian-American adolescents in Long Beach, California were compared to grade-
and gender-matched nationally representative data from the Monitoring the Future
study and data from the California Healthy Kids Survey of students within the
same school district. RESULTS: Overall, the Cambodian-American youth were less
likely than nationally- and regionally-representative youth to use alcohol,
marijuana, and cigarettes. Specifically, relative to estimates obtained for the
general population and students attending school in the same school district,
Cambodian-American youth were significantly less likely to use alcohol and
marijuana. Cambodian-American youth were also less likely than youth in the
general population to smoke cigarettes, but did not differ statistically from
youth within their same school district. CONCLUSIONS: As a group, Cambodian
American youth may not be at especially high risk for substance use. As is the
case with virtually all populations, some individuals within the Cambodian
American group are likely to have more difficulty than others with substance use
concerns. Thus, additional research is needed to identify factors that might help
to identify high users with potential service needs.
PMID- 25128640
TI - Lubricating recovery of damaged pleural mesothelium: effect of time and of
phosphatidylcholines.
AB - Effect of time and phosphatidylcholines (PCs) on lubrication of damaged
mesothelium has been investigated. Marked increase in coefficient of kinetic
friction (MU) of pleural specimens after mesothelial blotting and rewetting
decreased by 23.4+/-3.5%, 41.8+/-3.8%, and 40.5+/-2.7% after 30min, 1h, and 2h.
Hence, damaged mesothelium is able to partially reset lubricating molecules on
its surface. Increase in MU of post-blotting Ringer 2h after addition of
unsaturated PCs (3mg/ml) decreased a little more than after 2h Ringer. Effects of
unsaturated and saturated PCs were similar, contrary to expectation raised by
their different percentage in pleural and alveolar lavage. Effect of PCs did not
increase at 6mg/ml, and was nil at 0.4mg/ml. Increase of MU after short
phospholipase treatment decreased by 45.9+/-2.0% after 2h Ringer, and a little
more after addition of unsaturated or saturated PCs. Hence, PCs, as other
phospholipids, have a small effect, likely because of difficulty in resetting
their relationships with main lubricating molecules.
PMID- 25128641
TI - Influence of lung volume, fluid and capillary recruitment during positional
changes and exercise on thoracic impedance in heart failure.
AB - It is unclear how dynamic changes in pulmonary-capillary blood volume (Vc),
alveolar lung volume (derived from end-inspiratory lung volume, EILV) and
interstitial fluid (ratio of alveolar capillary membrane conductance and
pulmonary capillary blood volume, Dm/Vc) influence lung impedance (Z(T)). The
purpose of this study was to investigate if positional change and exercise result
in increased EILV, Vc and/or lung interstitial fluid, and if Z(T) tracks these
variables. METHODS: 12 heart failure (HF) patients underwent measurements (Z(T),
EILV, Vc/Dm) at rest in the upright and supine positions, during exercise and
into recovery. Inspiratory capacity was obtained to provide consistent measures
of EILV while assessing Z(T). RESULTS: Z(T) increased with lung volume during
slow vital capacity maneuvers (p<0.05). Positional change (upright->supine)
resulted in an increased Z(T) (p<0.01), while Vc increased and EILV and Dm/Vc
decreased (p<0.05). Moreover, during exercise Vc and EILV increased and Dm/Vc
decreased (p<0.05), whereas, Z(T) did not change significantly (p>0.05).
CONCLUSION: Impedance appears sensitive to changes in lung volume and body
position which appear to generally overwhelm small acute changes in lung fluid
when assed dynamically at rest or during exercise.
PMID- 25128642
TI - The effect of chronic low back pain on tactile suppression during back movements.
AB - The aim of the present study was to examine whether tactile suppression, the
phenomenon whereby tactile perception is suppressed during movement, would occur
in the context of back movements. Of particular interest, it was investigated if
tactile suppression in the back would be attenuated in those suffering from
chronic low back pain. Individuals with chronic low back pain (N = 30) and a
matched control group (N = 24) detected tactile stimuli on three possible
locations (back, arm, chest) while performing a back or arm movement, or no
movement. We hypothesized that the movements would induce tactile suppression,
and that this effect would be largest for low-intense stimuli on the moving body
part. We further hypothesized that, during back movements, tactile suppression on
the back would be less pronounced in the chronic low back pain group than in the
control group. The results showed the expected general tactile suppression
effects. The hypothesis of back-specific attenuation of tactile suppression in
the chronic low back pain group was not supported. However, back-specific tactile
suppression in the chronic low back pain group was less pronounced in those who
performed the back movements more slowly.
PMID- 25128643
TI - Application of a liquid chromatography-tandem mass spectrometry method to the
pharmacokinetics, tissue distribution and excretion studies of sweroside in rats.
AB - A sensitive, reliable and accurate high-performance liquid chromatography with
tandem mass spectrometry (HPLC-MS/MS) was developed and validated for the
quantification of sweroside in rat plasma, tissue and excretion. A single-step
protein precipitation by methanol was used to prepare samples. Sweroside and
swertiamarin (internal standard, IS) were separated by using a C18 column and a
mobile phase consisted of methanol and water containing 0.1% formic acid running
at a flow rate of 0.8ml/min for 6min. Detection and quantification were performed
using a mass spectrometer by the multiple-reaction monitoring (MRM) in positive
electrospray ionization mode. The optimized mass transition ion pairs (m/z) for
quantitation were [M+H](+)359.1->197.2 for sweroside and [M+Na](+)397.4->165.3
for swertiamarin (IS), respectively. The inter-day precision (RSD %) was less
than 11.20% and intra-day precision (RSD %) was less than 10.90%, while the inter
day accuracy (RE %) was ranged from -9.69 to 9.17% and intra-day accuracy (RE %)
was ranged from -10.56 to 13.47%. The mean elimination half-life (t1/2) of
sweroside for 5, 10 and 15mg/kg dose were 78.8, 67.6 and 77.2min, respectively.
And sweroside follows linear plasma pharmacokinetics across the investigated
dosage range in rats (5-15mg/kg). The absolute bioavailability (F %) of sweroside
was 11.90% on average. The results of tissue distribution showed the higher
sweroside concentrations were found in kidney, liver, spleen and lung, and the
small amount of drug was distributed into the brain tissue. The high distribution
in liver confirms the reports that sweroside has hepatoprotective activity and
promoted liver regeneration, and there was no long-term accumulation of sweroside
in rat tissues. Total recoveries of sweroside within 48h were 0.67% in bile,
1.55% in urine and 0.46% in feces, which might be resulted from liver first-pass
effect. The above results suggested that sweroside was mainly excreted as the
metabolites.
PMID- 25128644
TI - Trace elements in major marketed marine bivalves from six northern coastal cities
of China: concentrations and risk assessment for human health.
AB - One hundred and fifty nine samples of nine edible bivalve species (Argopecten
irradians, Chlamys farreri, Crassostrea virginica, Lasaea nipponica, Meretrix
meretrix, Mytilus edulis, Ruditapes philippinarum, Scapharca subcrenata and
Sinonovacula constricta) were randomly collected from eight local seafood markets
in six big cities (Dalian, Qingdao, Rizhao, Weifang, Weihai and Yantai) in the
northern coastal areas of China for the investigation of trace element
contamination. As, Cd, Cr, Cu, Hg, Pb and Zn were quantified. The risk of these
trace elements to humans through bivalve consumption was then assessed. Results
indicated that the concentrations of most of the studied trace element varied
significantly with species: the average concentration of Cu in C. virginica was
an order of magnitude higher than that in the remaining species; the average
concentration of Zn was also highest in C. virginica; the average concentration
of As, Cd and Pb was highest in R. philippinarum, C. farreri and A. irradians,
respectively. Spatial differences in the concentrations of elements were
generally less than those of interspecies, yet some elements such as Cr and Hg in
the samples from different cities showed a significant difference in
concentrations for some bivalve species. Trace element concentrations in edible
tissues followed the order of Zn>Cu>As>Cd>Cr>Pb>Hg generally. Statistical
analysis (one-way ANOVA) indicated that different species examined showed
different bioaccumulation of trace elements. There were significant correlations
between the concentrations of some elements. The calculated hazard quotients
indicated in general that there was no obvious health risk from the intake of
trace elements through bivalve consumption. But care must be taken considering
the increasing amount of seafood consumption.
PMID- 25128645
TI - Overexpression of a tobacco J-domain protein enhances drought tolerance in
transgenic Arabidopsis.
AB - DnaJ proteins constitute a DnaJ/Hsp40 family and are important regulators
involved in diverse cellular functions. To date, the molecular mechanisms of DnaJ
proteins involved in response to drought stress in plants are largely unknown. In
this study, a putative DnaJ ortholog from Nicotiana tabacum (NtDnaJ1), which
encodes a putative type-I J-protein, was isolated. The transcript levels of
NtDnaJ1 were higher in aerial tissues and were markedly up-regulated by drought
stress. Over-expression of NtDnaJ1 in Arabidopsis plants enhanced their tolerance
to osmotic or drought stress. Quantitative determination of H2O2 accumulation has
shown that H2O2 content increased in wild-type and transgenic seedlings under
osmotic stress, but was significantly lower in both transgenic lines compared
with the wild-type. Expression analysis of stress-responsive genes in NtDnaJ1
transgenic Arabidopsis revealed that there was significantly increased expression
of genes involved in the ABA-dependent signaling pathway (AtRD20, AtRD22 and
AtAREB2) and antioxidant genes (AtSOD1, AtSOD2, and AtCAT1). Collectively, these
data demonstrate that NtDnaJ1 could be involved in drought stress response and
its over-expression enhances drought tolerance possibly through regulating
expression of stress-responsive genes. This study may facilitate our
understandings of the biological roles of DnaJ protein-mediated abiotic stress in
higher plants and accelerate genetic improvement of crop plants tolerant to
environmental stresses.
PMID- 25128646
TI - Characterization of two highly similar CBF/DREB1-like genes, PhCBF4a and PhCBF4b,
in Populus hopeiensis.
AB - The C-repeat binding factors (CBFs)/dehydration-responsive element-binding
protein (DREBs) are a group of conserved transcription factors that play an
important role in the response and adaptation to environmental stress in many
plants. Two highly similar CBF/DREB1-like genes, PhCBF4a and PhCBF4b, were
previously identified in Populus hopeiensis. In this paper, we describe the
function of these proteins in detail in terms of abiotic stress tolerance.
Phylogenic analysis suggests that PhCBF4a and PhCBF4b are expressed as two
distinct alleles. Expression of both genes is induced mainly by dehydration, low
temperature, and high-salinity. Agroinfiltration experiments in tobacco leaves
revealed differential transcriptional activation of the genes, likely driven by
differences in their C-terminal regions. When constitutively expressed in
Arabidopsis, PhCBF4a and PhCBF4b induced elevated expression of the CBF/DREB1
regulons without prior stimulus, resulting in dwarfism, delayed flowering, and
greater drought tolerance compared with vector controls. These results
demonstrate that PhCBF4a and PhCBF4b are functional transcriptional regulators
involved in the response of P. hopeiensis to abiotic stresses.
PMID- 25128648
TI - Lysyl oxidase-like 2 (LOXL2) from stromal fibroblasts stimulates the progression
of gastric cancer.
AB - The aim of this study was to clarify the role of fibroblast-derived Lysyl oxidase
like 2 (LOXL2) in the development of gastric cancer. The correlation between the
clinicopathological features of 548 primary gastric carcinomas and LOXL2
expression in stromal cells was examined by immunohistochemistry. Two gastric
cancer cell lines, OCUM-12 and NUGC-3, and cancer-associated fibroblasts (CAFs)
were used in this in vitro study. The effect of fibroblast-derived LOXL2 on the
motility of gastric cancer cells was analyzed by using a wound-healing assay, a
double-chamber invasion assay, and western blot. LOXL2 expression in stromal
cells was significantly associated with tumor invasion depth, lymph node
metastasis, lymphatic invasion, venous invasion, and peritoneal dissemination.
Multivariable logistic regression analysis revealed that LOXL2 expression in
stromal cells could be an independent predictive parameter for the overall
survival of patients. CAFs significantly stimulated the migration and invasion of
OCUM-12 and NUGC-3 cells. This motility-stimulating ability of CAFs was inhibited
by LOXL2 siRNA. Western blot analysis indicated that phosphorylation of focal
adhesion kinase (FAK) in cancer cells was increased by the conditioned medium
from CAFs, and was decreased by the conditioned medium from LOXL2 siRNA-treated
CAFs. LOXL2 expression in stromal cells may be a useful prognostic factor for
patients with gastric cancer. Fibroblast-derived LOXL2 may stimulate the motility
of gastric cancer cells.
PMID- 25128647
TI - Exploring therapeutic potentials of baicalin and its aglycone baicalein for
hematological malignancies.
AB - Despite tremendous advances in the targeted therapy for various types of
hematological malignancies with successful improvements in the survival rates,
emerging resistance issues are startlingly high and novel therapeutic strategies
are urgently needed. In addition, chemoprevention is currently becoming an
elusive goal. Plant-derived natural products have garnered considerable attention
in recent years due to the potential dual functions as chemotherapeutics and
dietary chemoprevention. One of the particularly ubiquitous families is the
polyphenolic flavonoids. Among them, baicalin and its aglycone baicalein have
been widely investigated in hematological malignancies because both of them
exhibit remarkable pharmacological properties. This review focuses on the recent
achievements in drug discovery research associated with baicalin and baicalein
for hematological malignancy therapies. The promising anticancer activities of
these two flavonoids targeting diverse signaling pathways and their potential
biological mechanisms in different types of hematological malignancies, as well
as the combination strategy with baicalin or baicalein as chemotherapeutic
adjuvants for recent therapies in these intractable diseases are discussed.
Meanwhile, the biotransformation of baicalin and baicalein and the relevant
approaches to improve their bioavailability are also summarized.
PMID- 25128649
TI - Molecular mechanisms of endometrial stromal sarcoma and undifferentiated
endometrial sarcoma as premises for new therapeutic strategies.
AB - Endometrial stromal sarcoma (ESS) and undifferentiated endometrial sarcoma (UES)
are very rare gynecologic malignancies. Due to the rarity and heterogeneity of
these tumors, little is known about their epidemiology, pathogenesis, and
molecular pathology. Our previous studies have described deregulation of histone
deacetylases expression in ESS/UES samples. Some of these enzymes can be
inhibited by substances which are already approved for treatment of cutaneous T
cell lymphoma. On the basis of published data, they may also provide a
therapeutic option for ESS/UES patients. Our review focuses on molecular
mechanisms of ESS/UES. It describes various aspects with special emphasis on
alteration of histone deacetylation and its possible relevance for novel
therapies.
PMID- 25128650
TI - Embelin inhibits pancreatic cancer progression by directly inducing cancer cell
apoptosis and indirectly restricting IL-6 associated inflammatory and immune
suppressive cells.
AB - Pancreatic cancer is an aggressive malignancy and unresponsive to conventional
chemotherapies. Here, the anti-inflammatory and anti-tumor effects of embelin on
pancreatic cancer were investigated. Embelin significantly attenuated cells
invasion, proliferation and induced apoptosis through inhibition of STAT3 and
activation of p53 signaling pathways. Embelin substantially reduced the
tumorigenicity of pancreatic cancer cells in vivo, which was associated with
reduced inflammatory cells and immune suppressive cells, IL-17A(+) Th17, GM
CSF(+) Th, MDSCs and Treg, through inhibition of IL-6 secretion. Moreover,
embelin decrease IL-6-induced STAT3 phosphorylation. In summary, embelin
represents a novel therapeutic drug candidate for the clinical treatment of
pancreatic cancer.
PMID- 25128651
TI - An in vitro retinoblastoma human triple culture model of angiogenesis: a
modulatory effect of TGF-beta.
AB - Retinoblastoma is the most common intraocular tumour in children. In view of
understanding the molecular mechanisms through which angiogenic switch on happens
in the early phases of reciprocal interaction between tumour and cells
constituting retinal microvessel, Transwell co-cultures constituted by human
retinal endothelial cells (HREC), pericytes (HRPC), and human retinoblastoma cell
line Y-79 were performed. Y-79 enhanced HREC proliferation, reduced by the
introduction of HRPC in triple culture. In HREC/HRPC cultures, TGF-beta in media
increased, decreasing in triple cultures. High VEGF levels in triple cultures
witnessed the establishment of a strongly in vitro angiogenic environment. Y-79
induced in HREC an increase in c- and iPLA2, phospho-cPLA2, inducible COX-2
protein expressions, PLA2 activities and prostaglandin E2 (PGE2) release. These
effects were attenuated when HRPC were introduced in triple culture. Moreover,
antibody silencing of TGF-beta demonstrated a strong correlation between the
signalling pathway triggered by TGF-beta of pericytal origin and the
phospholipase activation and the modulation of PGE2 release. Inhibiting VEGFA
effect, the HRPC loss in triple culture decreased, showing its modulatory effect
on their survival. Relying on the data here presented, sustaining the pericytal
survival in a tumour retinal environment could ensure the integrity of
microvessels and the TGF-beta supply, essential for controlling aberrant
endothelial pruning and angiogenesis.
PMID- 25128652
TI - Betaglycan blocks metastatic behaviors in human granulosa cell tumors by
suppressing NFkappaB-mediated induction of MMP2.
AB - Metastatic ovarian granulosa cell tumors (GCT) exhibit loss of betaglycan. Here
we test the hypothesis that betaglycan blocks GCT metastasis by suppressing
NFkappaB/TGFbeta2-induced matrix metalloprotinease-2 (MMP2). Human GCT and a
human GCT cell model demonstrated prominent MMP2 expression, which was dependent
on NFkappaB activity and stimulated by TGFbeta2 in an NFkappaB-dependent manner.
Betaglycan suppressed both basal and TGFbeta2-induced MMP2 expression and
countered metastatic behaviors of GCT cells in non-adherent spheroid culture and
in vivo xenograft models of metastasis. These data suggest that NFkappaB/TGFbeta2
promotes, and betaglycan impedes, the early stages of GCT metastasis, when tumor
cells first invade the peritoneum.
PMID- 25128653
TI - Does lesioning surgery have a role in the management of multietiological tremor
in the era of Deep Brain Stimulation?
AB - INTRODUCTION: Surgical management of tremor has evolved over the years with Deep
Brain Stimulation (DBS) gradually supplanting lesioning as the mainstay in
treatment. In this article, the largest of its kind from our country, we present
our experience in the use of lesioning in the management of patients with
multietiological tremors. These include not only common indications like
Parkinson disease and essential tremor but also rare causes such as Pantothenate
kinase associated neurodegeneration (PKAN), multiple sclerosis (MS) and Wilson
disease. MATERIALS AND METHODS: Patients with medically refractory tremor who
underwent surgery were included in the analysis. A comprehensive clinical and
radiological evaluation was performed which was repeated 3 months postoperatively
and at successive visits. Video documentation of was obtained at all visits.
RESULTS: A total of 21 patients (18 men, 3 women) with an average age 37.7 years
(range 21-65 years) underwent stereotactic thalamotomy/subthalamotomy at our
institute between 2008 and 2013, for the treatment of medically refractory tremor
of varying etiologies. The mean preoperative duration of symptoms was 11 years
(range 10 months to 34 years). The median time to onset of improvement was 2
months (range 1 week to 8 months). Analyzing the improvement on the modified FTM
scale, in part 1 the scores improved from 21.7 to 1.5, the part II subset
improved from an average of 9.2 to 3.2 while the part III subset improved from an
average of 14.1 to 4.1 postoperatively. This implied an excellent response in
tremor while the other 2 components had a very good response. DISCUSSION: In this
study we have for the first time objectively analyzed the tremor improvement with
a modified FTM scale and have produced excellent results. We have also shown that
tremor of various etiologies respond extremely well to lesioning surgery. While
DBS continues to remain the treatment of choice in various types of bilateral
tremor, lesioning is very successful in a carefully selected cohort of patients.
We are of the opinion that in predominantly unilateral tremor or when the patient
cannot afford DBS especially in a country like ours, lesioning surgery is an
important tool in the armamentarium of the functional neurosurgeon.
PMID- 25128654
TI - Octyl-cyanoacrylate skin adhesive is effective for wound closure in posterior
spinal surgery without increased risk of wound complications.
AB - OBJECTIVE: Few published studies have examined the complication profile after
posterior spinal surgery wherein absorbable, subcuticular suture and
cyanoacrylate skin adhesives (CSA) were used for incision closure. The purpose of
this report is to compare the rate and profile of wound complications in a large
number of patients who underwent posterior spinal surgery with CSA skin closure
to rates of similar complications with standard nylon closure techniques.
METHODS: The prospective database of all surgical cases maintained by the senior
author was retrospectively reviewed. Three hundred eighty-two patients underwent
posterior spinal surgery for degenerative, oncologic and traumatic pathology.
Wound-related complications, including cerebrospinal fluid leak, wound infection
and dehiscence were analyzed in all patients. RESULTS: These data establish that
the incisions in patients who undergo posterior spinal surgery can be safely and
successfully closed with subcuticular MonocrylTM and CSA without increased risk
of CSF leak, wound infection or dehiscence. Rates of these complications were
similar between the study population, a small subset of patients treated with
traditional closure techniques and those in the established literature.
CONCLUSIONS: CSA is a safe method to achieve ultimate skin closure in patients
who undergo posterior spinal surgery without increased risk of wound-related
complications, even in those patients undergoing intradural procedures.
PMID- 25128655
TI - Epidemiology of a large telestroke cohort in the Delaware valley.
AB - BACKGROUND: The American Heart Association/American Stroke Association has
recently endorsed telestroke. Telestroke has enhanced stroke diagnosis, increased
tPA administration and improved long-term outcomes. However, many of the
publication on telemedicine so far have been review articles. OBJECTIVES: We
investigated the epidemiological features of telestroke patients and evaluated
the difference between the transferred and non-transferred cohorts. METHODS: We
collected data on telestroke consultation, between January 2012 and June 2013,
regarding patient's age, gender, diagnosis, NIHSS, onset-to-spoke time (OTS), tPA
administration and transfer status. Further data was obtained on transferred
patients regarding discharge and endovascular interventions. RESULTS: The means
of age, NIHSS and OTS time were the following: 67.59 years, 7.65 and 11.28h
respectively. The proportion of transferred patients was 12.04% (280/2324); lower
than what was previously reported. The overall rate of IV tPA administration was
11.98%. Transferred patients had a significantly higher NIHSS mean (10.93 vs.
6.73; P<0.001), and were more likely to have received IV-tPA at onset (25.57 vs.
9.67; P<0.001). The age, gender proportion, stroke mimic proportion, and the mean
of OTS did not differ between the two-groups (0.49 vs. 0.31; P=0.38). A logistic
regression showed that NIHSS (OR=1.06, P<0.001) and tPA administration at onset
(OR=2.78, P<0.001) predict the transfer. Of the transferred patients, 4.5%
received endovascular intervention. The mortality rate of transferred patients
was 12.9%. Other outcomes were the following: 52% discharge to rehabilitation
facilities, 29% discharge to home, and 8% discharge to long-term nursing
facilities. CONCLUSION: Telestroke network is increasing the frequency of tPA
usage in acute ischemic stroke and may decrease the need for transfer. Our aim
was to optimize the stroke therapy to shorten the hospital stay and to increase
the discharge home. This allows a better functional outcome and an additional
benefit of cost-saving for the hospitals.
PMID- 25128656
TI - Hemiballism-hemidystonia after parietal lobe tumour resection.
PMID- 25128657
TI - WITHDRAWN: The instability of Cdc42 network with graph-theoretic methods.
AB - This article has been withdrawn at the request of the author(s) and/or editor due
to some inconsistencies in the manuscript. The Publisher apologizes for any
inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can
be found at http://www.elsevier.com/locate/withdrawalpolicy.
PMID- 25128658
TI - A model for enhanced and selective transport through biological membranes with
alternating pores.
AB - We investigate the outflux of ions through the channels in a cell membrane. The
channels undergo an open/close cycle according to a periodic schedule. Our study
is based both on theoretical considerations relying on homogenization theory, and
on Monte Carlo numerical simulations. We examine the onset of a limiting boundary
behavior characterized by a constant ratio between the outflux and the local
density, in the large volume limit. The focus here is on the issue of
selectivity, that is on the different behavior of the ion currents through the
channel in the cases of the selected and non-selected species.
PMID- 25128659
TI - Dynamic neural network-based robust observers for uncertain nonlinear systems.
AB - A dynamic neural network (DNN) based robust observer for uncertain nonlinear
systems is developed. The observer structure consists of a DNN to estimate the
system dynamics on-line, a dynamic filter to estimate the unmeasurable state and
a sliding mode feedback term to account for modeling errors and exogenous
disturbances. The observed states are proven to asymptotically converge to the
system states of high-order uncertain nonlinear systems through Lyapunov-based
analysis. Simulations and experiments on a two-link robot manipulator are
performed to show the effectiveness of the proposed method in comparison to
several other state estimation methods.
PMID- 25128660
TI - Irreversible membrane fouling abatement through pre-deposited layer of
hierarchical porous carbons.
AB - In this work, dual-templated hierarchical porous carbons (HPCs), produced from a
coupled ice-hard templating approach, are shown to be a highly effective solution
to the commonly occurring problem of irreversible fouling of low-pressure
membranes used for pre-treatment in wastewater reuse. For the first time, dual
templated HPCs, along with their respective counterparts - single-templated meso
porous carbon (MPCs) (without macropores) - are tested in terms of their fouling
reduction capacity and ability to remove different effluent organic matter
fractions present in wastewater and compared with a commercially available
powdered activated carbon (PAC). The synthesized HPCs provided exceptional
fouling abatement, a 4-fold higher fouling reduction as compared to the
previously reported best performing commercial PAC and ~2.5-fold better fouling
reduction than their respective mesoporous counterpart. Thus, it is shown that
not only mesoporosity, but macroporosity is also necessary to achieve high
fouling reduction, thus emphasizing the need for dual templating. In the case of
HPCs, the pre-deposition technique is also found to outperform the traditional
sorbent-feed mixing approach, mainly in terms of removal of fouling components.
Based on their superior performance, a high permeability (ultra-low-pressure)
membrane consisting of the synthesized HPC pre-deposited on a large pore size
membrane support (0.45 MUm membrane), is shown to give excellent pre-treatment
performance for wastewater reuse application.
PMID- 25128661
TI - Mode of membrane insertion of individual transmembrane segments in Mdl1 and Mdl2,
multi-spanning mitochondrial ABC transporters.
AB - The sorting of an individual transmembrane (TM) segment of multi-spanning
membrane proteins by the TIM23 complex in the mitochondrial inner membrane is
poorly understood. Using the Mgm1 fusion approach, we attempted to assess the
membrane insertion of individual TM segments of Mdl1p and Mdl2p, mitochondrial
ABC transporters. Although these transporters share high sequence similarity, our
results show that their membrane sorting patterns differ and that specific
residues in TM domains strongly influence membrane insertion or translocation.
These data imply that TIM23-mediated membrane insertion highly depends on the TM
domain sequence context.
PMID- 25128662
TI - I want to quit education: a longitudinal study of stress and optimism as
predictors of school dropout intention.
AB - Prior research on school dropout has often focused on stable person- and
institution-level variables. In this research, we investigate longitudinally
perceived stress and optimism as predictors of dropout intentions over a period
of four years, and distinguish between stable and temporary predictors of dropout
intentions. Findings based on a nationally representative sample of 16-20 year
olds in Switzerland (N = 4312) show that both average levels of stress and
optimism as well as annually varying levels of stress and optimism affect dropout
intentions. Additionally, results show that optimism buffers the negative impact
of annually varying stress (i.e., years with more stress than usual), but not of
stable levels of stress (i.e., stress over four years). The implications of the
results are discussed according to a dynamic and preventive approach of school
dropout.
PMID- 25128663
TI - Toxoplasma gondii and Neospora caninum infections in goat abortions from
Argentina.
AB - The aims of this study were to identify the occurrence of Toxoplasma gondii and
Neospora caninum abortions in goats from Argentina by serological, macroscopical
and microscopical examination and bioassay, and to characterize the obtained
isolates by molecular techniques. For this purpose, 25 caprine fetal fluids, 18
caprine fetal brains and 10 caprine placentas from 8 dairy/meat goat farms from
Argentina were analyzed. Gestational age of the aborted fetuses was determined in
18 cases. Protozoal infections were detected by at least one of the applied
diagnostic techniques in 44% (11/25) of examined fetuses; specifically, 24%
(6/25) were positive to T. gondii, 8% (2/25) were positive to N. caninum and 12%
(3/25) were positive to both parasites. In this study IFAT titers were similarly
distributed in younger and older fetuses. Macroscopical and microscopical
examination of one placenta revealed chalky nodules in the fetal cotyledons and
normal intercotyledonary areas, as well as necrosis and calcification of
mesenchymal cells in villi. Tachyzoites were observed in peritoneal wash from 2
mice inoculated with brain and a pool of brain and placenta of two fetuses. Cell
culture growth of tachyzoites was achieved from one inoculated mouse, and
confirmed as T. gondii by PCR. The T. gondii isolate was identified as atypical
or non-canonical by nested-PCR-RFLP. This is the first study that investigated
the involvement of N. caninum and T. gondii in cases of goat abortion in
Argentina.
PMID- 25128665
TI - Synthesis of natural-like acylphloroglucinols with anti-proliferative, anti
oxidative and tube-formation inhibitory activity.
AB - Two series of natural and natural-like mono- and bicyclic acylphloroglucinols
derived from secondary metabolites in the genus Hypericum (Hypericaceae) were
synthesised and tested in vitro for anti-proliferative and tube-formation
inhibitory activity in human microvascular endothelial cells (HMEC-1). In
addition, their anti-oxidative activity was determined via an ORAC-assay. The
first series of compounds (4a-e) consisted of geranylated monocyclic
acylphloroglucinols with varying aliphatic acyl substitution patterns, which were
subsequently cyclised to the corresponding 2-methyl-2-prenylchromane derivatives
(5a and 5d). The second series involved compounds containing a 2,2
dimethylchromane skeleton with differing aromatic acyl substitution (6a-d and 7a
e). Compound 7a, (5,7-dihydroxy-2,2-dimethylchroman-6-yl)-(3,4
dihydroxyphenyl)methanone), showed the highest in vitro anti-proliferative
activity with an IC50 of 0.88 +/- 0.08 MUM and a remarkable anti-oxidative
activity of 2.8 +/- 0.1 TE from the ORAC test. Interestingly, the high anti
proliferative activity of these acylphloroglucinols was not associated with tube
formation inhibition. Compounds (E)-1-(3-(3,7-dimethylocta-2,6-dien-1-yl)-2,4,6
trihydroxyphenyl)-2-methylbutan-1-one (4d) and (5,7-dihydroxy-2,2-dimethylchroman
6-yl)(3,4-dimethoxyphenyl)methanone (6a) exhibited moderate to weak anti
proliferative effects (IC50 11.0 +/- 1 MUM and 48.0 +/- 4.3 MUM, respectively)
and inhibited the capillary-like tube formation of HMEC-1 in vitro, whereas 7a
was inactive. The most active compound in the ORAC assay was 7c, which exhibited
an anti-oxidative effect of 6.6 +/- 1.0 TE. However, this compound showed only
weak activity during the proliferation assay (IC50 53.8 +/- 0.3) and did not
inhibit tube-formation.
PMID- 25128664
TI - Identification of anxiety sensitivity classes and clinical cut-scores in a sample
of adult smokers: results from a factor mixture model.
AB - Anxiety sensitivity (AS), a multidimensional construct, has been implicated in
the development and maintenance of anxiety and related disorders. Recent evidence
suggests that AS is a dimensional-categorical construct within individuals.
Factor mixture modeling was conducted in a sample of 579 adult smokers (M
age=36.87 years, SD=13.47) to examine the underlying structure. Participants
completed the Anxiety Sensitivity Index-3 and were also given a Structured
Clinical Interview for DSM-IV-TR. Three classes of individuals emerged, a high AS
(5.2% of the sample), a moderate AS (19.0%), and a normative AS class (75.8%). A
cut-score of 23 to identify high AS individuals, and a cut-score of 17 to
identify moderate-to-high AS individuals were supported in this study. In
addition, the odds of having a concurrent anxiety disorder (controlling for other
Axis I disorders) were the highest in the high AS class and the lowest in the
normative AS class.
PMID- 25128666
TI - Novel alkylphospholipid-DTC hybrids as promising agents against endocrine related
cancers acting via modulation of Akt-pathway.
AB - A new series of 2-(alkoxy(hydroxy)phosphoryloxy)ethyl dialkylcarbodithioate
derivatives was synthesized and evaluated against endocrine related cancers,
acting via modulation of Akt-pathway. Eighteen compounds were active at 7.24-100
MUM against MDA-MB-231 or MCF-7 cell lines of breast cancer. Three compounds (14,
18 and 22) were active against MCF-7 cells at IC50 significantly better than
miltefosine and most of the compounds were less toxic towards non-cancer cell
lines, HEK-293. On the other hand, twelve compounds exhibited cell growth
inhibiting activity against prostate cancer cell lines, either PC-3 or DU-145 at
14.69-95.20 MUM. While nine of these were active against both cell lines. The
most promising compounds 14 and 18 were about two and five fold more active than
miltefosine against DU-145 and MCF-7 cell lines respectively and significantly
down regulated phospho-Akt. Possibly anti-cancer and pro-apoptotic activity was
mostly due to blockade of Akt-pathway.
PMID- 25128667
TI - Chalcone based azacarboline analogues as novel antitubulin agents: design,
synthesis, biological evaluation and molecular modelling studies.
AB - The present study involves the design of a series of 3-aryl-9-acetyl
pyridazino[3,4-b]indoles as constrained chalcone analogues. A retrosynthetic
route was proposed for the synthesis of target compounds. All the synthesized
compounds were evaluated for in-vitro cytotoxicity against THP-1, COLO-205, HCT
116 and A-549 human cancer cell lines. The results indicated that 2a, 3a, 5a and
6a possessed significant cytotoxic potential with an IC50 value ranging from 1.13
to 5.76 MUM. Structure activity relationship revealed that the nature of both
Ring A and Ring B influences the activity. Substitution of methoxy groups on the
phenyl ring (Ring A) and unsubstituted phenyl ring (Ring B) were found to be the
preferred structural features. The most potent compound 2a was further tested for
tubulin inhibition. Compound 2a was found to significantly inhibit the tubulin
polymerization (IC50 value - 2.41 MUM against THP-1). Compound 2a also caused
disruption of microtubule assembly as evidenced by Immunoflourescence technique.
The significant cytotoxicity and tubulin inhibition by 2a was rationalized by
molecular modelling studies. The most potent structure was docked at colchicine
binding site (PDB ID-1SA0) and was found to be stabilized in the cavity via
various hydrophobic and hydrogen bonding interactions.
PMID- 25128668
TI - Statins in therapy: understanding their hydrophilicity, lipophilicity, binding to
3-hydroxy-3-methylglutaryl-CoA reductase, ability to cross the blood brain
barrier and metabolic stability based on electrostatic molecular orbital studies.
AB - The atomic electrostatic potentials calculated by the CHELPG method have been
shown to be sensitive indicators of the gas phase and solution properties of the
statins. Solvation free energies in water, n-octanol and n-octane have been
determined using the SMD solvent model. The percentage hydrophilicity and
hydrophobicity (or lipophilicity) of the statins in solution have been determined
using (a) the differences in solvation free energies between n-octanol and n
octane as a measure of hydrophilicity, and the solvation energy in octane as a
measure of hydrophobicity (b) the sum of the atomic electrostatic charges on the
hydrogen bonding and polar bonding nuclei of the common pharmacophore combined
with a solvent measure of hydrophobicity, and (c) using the buried surface areas
after statin binding to HMGCR to calculate the hydrophobicity of the bound
statins. The data suggests that clinical definitions of statins as either
"hydrophilic" or "lipophilic" based on experimental partition coefficients are
misleading. An estimate of the binding energy between rosuvastatin and HMGCR has
been made using: (a) a coulombic electrostatic interaction model, (b) the
calculated desolvation and resolvation of the statin in water, and (c) the first
shell transfer solvation energy as a proxy for the restructuring of the water
molecules immediately adjacent to the active binding site of HMGCR prior to
binding. Desolvation and resolvation of the statins before and after binding to
HMGCR are major determinants of the energetics of the binding process. An
analysis of the amphiphilic nature of lovastatin anion, acid and lactone and
fluvastatin anion and their abilities to cross the blood brain barrier has
indicated that this process may be dominated by desolvation and resolvation
effects, rather than the statin molecular size or statin-lipid interactions
within the bilayer. The ionization energy and electron affinity of the statins
are sensitive physical indicators of the ease that the various statins can
undergo endogenous oxidative metabolism. The absolute chemical hardness is also
an indicator of the stability of the statins, and may be a useful indicator for
drug design.
PMID- 25128669
TI - Investigation of in vitro anticancer and DNA strap interactions in live cells
using carboplatin type Cu(II) and Zn(II) metalloinsertors.
AB - A series of carboplatin type Cu(II) and Zn(II) metalloinsertors (1-8) having beta
diketone analogues and biologically significant cyclobutane-1,1-dicarboxylic acid
have been synthesized and characterized by spectral and analytical methods. The
binding and cleavage propensity of these metalloinsertors on DNA and their
cytotoxic effects in live cells have been explored. From the gel electrophoresis
study, it is observed that the complexes 1-8 cleave pBR322 DNA via a hydrolytic
mechanism induced by hydroxyl radical scavengers, DMSO and EtOH as the reactive
oxygen species (ROS). In vivo antitumor efficacy has been studied on EAC tumor
bearing mice which is assessed by mean survival time, effect on hematological
parameters and solid tumor volume. The results strongly support that complex 1
shows potent antitumor effect against EAC and higher than the standard drug
carboplatin. Moreover, the cytotoxicity of the complexes, screened on a panel of
human cancerous cell lines viz., human cervical cancer cells (HeLa), human breast
adenocarcinoma cells (MCF-7), human laryngeal epithelial carcinoma cells (HEp-2),
human liver carcinoma cells (Hep G2) and non-cancerous NIH 3T3 mouse embryonic
fibroblasts cell lines, reveals that complex 1 exhibits a better anticancer
activity than other complexes and standards.
PMID- 25128670
TI - Present status of quinoxaline motifs: excellent pathfinders in therapeutic
medicine.
AB - Quinoxalines belong to a class of excellent heterocyclic scaffolds owing to their
wide biological properties and diverse therapeutic applications in medicinal
research. They are complementary in shapes and charges to numerous biomolecules
they interact with, thereby resulting in increased binding affinity. The
pharmacokinetic properties of drugs bearing quinoxaline cores have shown them to
be relatively easy to administer either as intramuscular solutions, oral capsules
or rectal suppositories. This work deals with recent advances in the synthesis
and pharmacological diversities of quinoxaline motifs which might pave ways for
novel drugs development.
PMID- 25128671
TI - Structure-activity relationships and molecular modeling studies of novel
arylpiperazinylalkyl 2-benzoxazolones and 2-benzothiazolones as 5-HT(7) and 5
HT(1A) receptor ligands.
AB - A novel series of arylpiperazinylalkyl 2-benzoxazolones and 2-benzothiazolones 18
38 was designed, synthesized and tested to evaluate their affinity for the 5-HT7
and 5-HT1A receptors. Compounds with a 2-benzothiazolone nucleus generally had
affinity values higher than the corresponding 2-benzoxazolone compounds. In
particular, derivatives possessing a six or seven carbon chain linker between 2
benzothiazolone and arylpiperazine had Ki values in the subnanomolar range for
the 5-HT1A receptor and in the low nanomolar range for the 5-HT7 receptor,
indicating that they may be interesting dual ligands. Molecular modeling studies
revealed different docking poses for the investigated compounds in homology
models of 5-HT1A and 5-HT7 receptors, which explained their experimentally
determined affinities and general low selectivity. Additionally, structural
interaction fingerprints analysis identified the important amino acid residues
for the specific interactions of long-chain arylpiperazines within the binding
pockets of both serotonin receptors.
PMID- 25128672
TI - The impact of REACH on classification for human health hazards.
AB - The REACH Regulation represents a major piece of chemical legislation in the EU
and requires manufacturers and importers of chemicals to assess the safety of
their substances. The classification of substances for their hazards is one of
the crucial elements in this process. We analysed the effect of REACH on
classification for human health endpoints by comparing information from REACH
registration dossiers with legally binding, harmonised classifications. The
analysis included 142 chemicals produced at very high tonnages in the EU, the
majority of which have already been assessed in the past. Of 20 substances
lacking a harmonised classification, 12 chemicals were classified in REACH
registration dossiers. More importantly, 37 substances with harmonised
classifications for human health endpoints had stricter classifications in
registration dossiers and 29 of these were classified for at least one additional
endpoint not covered by the harmonised classification. Substance-specific
analyses suggest that one third of these additional endpoints emerged from
experimental studies performed to fulfil information requirements under REACH,
while two thirds resulted from a new assessment of pre-REACH studies. We conclude
that REACH leads to an improved hazard characterisation even for substances with
a potentially good data basis.
PMID- 25128673
TI - Reducing the number of fish in bioconcentration studies with general chemicals by
reducing the number of test concentrations.
AB - Fish bioconcentration test guidelines generally require that bioconcentration
factors (BCFs) are determined at two exposure concentrations. However, recent
revisions to the OECD test guideline for bioconcentration testing (TG 305)
provide the option to use only one exposure concentration, when justification is
provided, although two concentrations may still be required for some regulatory
purposes. Recently, this justification has been demonstrated for plant protection
product active ingredients. To determine whether this justification has a broader
validity for general chemicals, an analysis of 236 BCF studies on general
chemicals was conducted. The results presented here again demonstrate that BCF
values do not significantly differ between concentrations when more than one
concentration is used. This relationship is particularly strong for BCFs
?1000L/kg, which is beneficial, since only chemicals with BCFs >2000L/kg may
require regulatory action. This analysis therefore provides a data-driven
rationale for using the one test concentration approach for general chemical
substances and thus could contribute to a substantial reduction in the use of
fish in bioconcentration tests.
PMID- 25128674
TI - Spectroscopic, crystal structural and electrochemical studies of zinc(II)-Schiff
base complex obtained from 2,3-diaminobenzene and 2-hydroxy naphthaldehyde.
AB - Mononuclear zinc(II) complex, [Zn(II)L], where L is a dianionic ligand, has been
synthesized and characterized by elemental analysis, electronic, IR and NMR
[(1)H, (13)C, DEPT, (1)H-(1)H COSY, ROESY, HSQC and HMBC] spectroscopic
techniques. Structural analysis of the complex by single crystal X-ray
crystallography shows the presence of a distorted square planar coordination
geometry (NNOO) of the metal center. The crystal of the title complex
C28H18N2O2Zn belongs to the orthorhombic system with space group Pmn21.
Electrochemical behavior of the Zn(II)L complex has been investigated by cyclic
voltammetry on glassy carbon and platinum electrodes in DMF at 100 mV/s scan
rate.
PMID- 25128675
TI - Degradation of environment pollutant dyes using phytosynthesized metal
nanocatalysts.
AB - We present for the first time biogenic reduction and stabilization of gold and
silver ions at room temperature using fruit juice of Punica granatum. The
formation, morphology and crystalline structure of the synthesized nanoparticles
are determined using UV-Visible, XRD and TEM. An attempt to reveal the partial
role of phenolic hydroxyls in the reduction of Au(3+) and Ag(+) is done through
FTIR analysis. The synthesized nanoparticles are used as potential catalysts in
the degradation of a cationic phenothiazine dye, an anionic mono azo dye and a
cationic fluorescent dye. The calculated values of percentage removal of dyes and
the rate constants from pseudo first order kinetic data fit give a comparative
study on degradation of organic dyes in presence of prepared gold and silver
nanoparticles.
PMID- 25128676
TI - Activity study of biogenic spherical silver nanoparticles towards microbes and
oxidants.
AB - The eco-friendly approach for the green synthesis of silver nanoparticles (SNP)
using Terminalia bellirica (T. bellirica) fruit extract is reported herein.
Initially formation of SNP was noticed through visual color change from yellow to
reddish brown and further analyzed by surface plasmonic resonance (SPR) band at
429 nm using UV-Vis spectroscopy. Identification of different polyphenols present
in T. bellirica extract was done using High Pressure Liquid Chromatography
(HPLC). Aqueous T. bellirica extract contains high amount of gallic acid which is
major secondary metabolite responsible for the reduction and stabilization
process. It was established by analyses of extracts before and after reduction
using HPLC. Formation of spherical SNP was characterized by Transmission Electron
Microscopy (TEM) analysis. X-ray Diffraction (XRD) study revealed crystalline
nature of SNP. Presence of different functional groups on the surface of SNP was
evidenced by Fourier Transform Infrared Spectroscopy (FTIR) study. A plausible
mechanism of reduction and stabilization processes involved in the synthesis of
stable SNP was also explained based on HPLC and FTIR data. In addition, the
synthesized SNP was tested for antibacterial and antioxidant activities. SNP
showed good antimicrobial activity against both gram positive (S. aureus) and
gram negative (E. coli) bacteria. It also showed good antioxidant activity
compared to ascorbic acid as standard antioxidant by using standard DPPH method.
PMID- 25128677
TI - Corona discharge ionization of paracetamol molecule: peak assignment.
AB - Ionization of paracetamol was investigated using ion mobility spectrometry
equipped with a corona discharge ionization source. The measurements were
performed in the positive ion mode and three peaks were observed in the ion
mobility spectrum. Experimental evidence and theoretical calculations were used
to correlate the peaks to related ionic species of paracetamol. Two peaks were
attributed to protonated isomers of paracetamol and the other peak was attributed
to paracetamol fragment ions formed by dissociation of the N-C bond after
protonation of the nitrogen atom. It was observed that three sites of paracetamol
compete for protonation and their relative intensities, depending on the sample
concentration. The ratio of ion products could be predicted from the internal
proton affinity of the protonation sites at each concentration.
PMID- 25128678
TI - Vibrational spectroscopic studies and molecular docking of 10,10
Dimethylanthrone.
AB - FT-IR and FT-Raman spectra of 10,10-Dimethylanthrone were recorded and analyzed.
The vibrational wavenumbers were computed using DFT quantum chemical
calculations. The data obtained from wavenumber calculations are used to assign
vibrational bands obtained experimentally. In its most stable form, the title
compound maintains C2v symmetry as determined by XRD results, where both methyl
groups are staggered with respect to the corresponding C23-C24 and C23-C28 bonds.
The geometrical parameters (B3LYP/6-311++G(d,p)(5D,7F)) of the title compound are
in agreement with the XRD results. The calculated HOMO and LUMO energies allow
the calculations of atomic and molecular properties and they also showed that
charge transfer occurs in the molecule. A detailed molecular picture of the title
compound and its interactions were obtained from NBO analysis. As seen from the
MEP map, negative potential regions are localized over the carbonyl group and are
possible sites for electrophilic attack. The title compound, 10,10
Dimethylanthrone forms a stable complex with human topoisomerase-II as is evident
from the ligand-receptor interactions and show appreciable antineoplastic
activity.
PMID- 25128679
TI - CuO nanostructures: optical properties and morphology control by pyridinium-based
ionic liquids.
AB - Copper oxide nanostructures have been synthesized by a simple reflux method in
aqueous medium of pyridinium based ionic liquids. The structural and optical
properties of CuO nanostructures were characterized by X-ray diffraction (XRD),
scanning electron microscopy (SEM), photoluminescence spectroscopy (PL) and UV
visible. The morphologies of the nanostructures can be controlled by changing the
amount of NaOH and ionic liquids. The results show that the use identical
pyridinium based ionic liquids in ratio of 4:1 NaOH/Cu(OAc)2?H2O yield minor
differences in morphology of CuO nanostructures. Different morphologies of CuO
nanostructures were obtained by changing the ratio NaOH/Cu(OAc)2?H2O to 2:1.
Ionic liquids play an important role on optical properties of CuO nanostructures.
The results of optical measurements of the CuO nanostructures illustrate that
band gaps are estimated to be 1.67-1.85 eV. PL patterns studies show that the
ionic liquids can be effect on PL patterns of the samples. The reasons of these
phenomena are discussed.
PMID- 25128680
TI - Investigation on the interaction between an antimicrobial in aquaculture,
malachite green and hemocyanin from mud crab Scylla paramamosain.
AB - Interaction between malachite green and hemocyanin of crab plays a crucial role
in the metabolism, distribution, and efficacy of toxic dyes in aquaculture. The
mechanism of interaction between malachite green and Hc from mud crab was studied
by using multi-spectral methods and molecular modeling in this work. The
spectroscopic and thermodynamic data show that the interaction is a spontaneous
process with the estimated enthalpy and entropy changes of -14.85(+/-1.86) kJ
mol(-1) and 30.38(+/-5.21) J mol(-1) K(-1), respectively. The binding sites of
malachite green in hemocyanin mainly locate in the interface of protein. The
hydrophobic and electrostatic forces are the primary contributors to the
interaction between hemocyanin and malachite green. The results of ultraviolet
vis absorbance, circular dichroism, and synchronous fluorescence spectroscopy
suggest that the binding of malachite green to hemocyanin induces some
conformational changes of protein.
PMID- 25128681
TI - Synthesis of zinc chlorophyll materials for dye-sensitized solar cell
applications.
AB - To design sensitizers for dye sensitized solar cells (DSSCs), a series of zinc
chlorins with different substituents were synthesized. Novel zinc methyl 3
devinyl-3-hydroxymethyl-20-phenylacetylenylpyropheophorbide-a (ZnChl-1), zinc
methyl 20-bromo-3-devinyl-3-hydroxymethylpyropheophorbide-a (ZnChl-2), zinc
methyl 3-devinyl-3-hydroxymethyl-pyropheophorbide-a (ZnChl-3), zinc propyl 3
devinyl-3-hydroxymethyl-pyropheophorbide-a (ZnChl-4) were synthesized and their
photovoltaic performances were evaluated in dye-sensitized solar cells.
Photoelectrodes with a 7 MUm thick nanoporous layer and a 5 MUm thick light
scattering layer were used to fabricate dye sensitized solar cells. The best
efficiency was obtained with ZnChl-2 sensitizer. ZnChl-2 gave a Jsc of 3.5
mA/cm(2), Voc of 412 mV, FF of 0.56 and an overall conversion efficiency of 0.81
at full sun (1000 W m(-2)).
PMID- 25128682
TI - Synthesis, spectroscopic and electrochemical performance of pasted beta-nickel
hydroxide electrode in alkaline electrolyte.
AB - beta-Nickel hydroxide (beta-Ni(OH)2) was successfully synthesized using
precipitation method. The structure and property of the beta-Ni(OH)2 were
characterized by X-ray diffraction (XRD), Fourier Transform infra-red (FT-IR),
Raman spectra and thermal gravimetric-differential thermal analysis (TG-DTA). The
results of the FTIR spectroscopy and TG-DTA studies indicate that the beta
Ni(OH)2 contains water molecules and anions. The microstructural and composition
studies have been performed using Scanning Electron Microscopy (SEM) and Energy
Dispersive X-ray (EDX) analysis. A pasted-type electrode is prepared using beta
Ni(OH)2 powder as the active material on a nickel sheet as a current collector.
Cyclic voltammetry (CV) and Electrochemical impedance spectroscopy (EIS) studies
were performed to evaluate the electrochemical performance of the beta-Ni(OH)2
electrode in 6M KOH electrolyte. CV curves showed a pair of strong redox peaks as
a result of the Faradaic redox reactions of beta-Ni(OH)2. The proton diffusion
coefficient (D) for the present beta-Ni(OH)2 electrode material is found to be
1.44*10(-12) cm(2) s(-1). Further, electrochemical impedance studies confirmed
that the beta-Ni(OH)2 electrode reaction processes are diffusion controlled.
PMID- 25128684
TI - Fusion of multi-tracer PET images for dose painting.
AB - PET imaging with FluoroDesoxyGlucose (FDG) tracer is clinically used for the
definition of Biological Target Volumes (BTVs) for radiotherapy. Recently, new
tracers, such as FLuoroThymidine (FLT) or FluoroMisonidazol (FMiso), have been
proposed. They provide complementary information for the definition of BTVs. Our
work is to fuse multi-tracer PET images to obtain a good BTV definition and to
help the radiation oncologist in dose painting. Due to the noise and the partial
volume effect leading, respectively, to the presence of uncertainty and
imprecision in PET images, the segmentation and the fusion of PET images is
difficult. In this paper, a framework based on Belief Function Theory (BFT) is
proposed for the segmentation of BTV from multi-tracer PET images. The first step
is based on an extension of the Evidential C-Means (ECM) algorithm, taking
advantage of neighboring voxels for dealing with uncertainty and imprecision in
each mono-tracer PET image. Then, imprecision and uncertainty are, respectively,
reduced using prior knowledge related to defects in the acquisition system and
neighborhood information. Finally, a multi-tracer PET image fusion is performed.
The results are represented by a set of parametric maps that provide important
information for dose painting. The performances are evaluated on PET phantoms and
patient data with lung cancer. Quantitative results show good performance of our
method compared with other methods.
PMID- 25128683
TI - Automatic atlas-based three-label cartilage segmentation from MR knee images.
AB - Osteoarthritis (OA) is the most common form of joint disease and often
characterized by cartilage changes. Accurate quantitative methods are needed to
rapidly screen large image databases to assess changes in cartilage morphology.
We therefore propose a new automatic atlas-based cartilage segmentation method
for future automatic OA studies. Atlas-based segmentation methods have been
demonstrated to be robust and accurate in brain imaging and therefore also hold
high promise to allow for reliable and high-quality segmentations of cartilage.
Nevertheless, atlas-based methods have not been well explored for cartilage
segmentation. A particular challenge is the thinness of cartilage, its relatively
small volume in comparison to surrounding tissue and the difficulty to locate
cartilage interfaces - for example the interface between femoral and tibial
cartilage. This paper focuses on the segmentation of femoral and tibial
cartilage, proposing a multi-atlas segmentation strategy with non-local patch
based label fusion which can robustly identify candidate regions of cartilage.
This method is combined with a novel three-label segmentation method which
guarantees the spatial separation of femoral and tibial cartilage, and ensures
spatial regularity while preserving the thin cartilage shape through anisotropic
regularization. Our segmentation energy is convex and therefore guarantees
globally optimal solutions. We perform an extensive validation of the proposed
method on 706 images of the Pfizer Longitudinal Study. Our validation includes
comparisons of different atlas segmentation strategies, different local
classifiers, and different types of regularizers. To compare to other cartilage
segmentation approaches we validate based on the 50 images of the SKI10 dataset.
PMID- 25128685
TI - Providers' perspectives on treating psychogenic nonepileptic seizures:
frustration and hope.
AB - Recent diagnostic and treatment advances in psychogenic nonepileptic seizures
(PNES) have the potential to improve care for patients, but little is known about
the current state of PNES care delivery in the Veterans Health Administration
(VA). We conducted semistructured interviews with 74 health-care clinicians and
workers in the VA, eliciting provider perceptions of PNES care. Data were
analyzed according to principles of Grounded Theory. The results revealed
variation in care and two emergent domain themes of frustration and hope.
Frustration was manifest in subthemes including Complexity, Patient Acceptance,
Uncertainty About Treatment, Need for Evidence-based Treatment, and Failure of
Cross-Disciplinary Collaboration between neurologists and mental health
providers. Hope encompassed subthemes of Positive Attitudes, Developing Cross
Disciplinary Treatment, and Specific PNES Care. Increased resources for
diagnosing, treating, and researching PNES have improved awareness of the
disorder. More research is needed to understand patients' and caregivers'
perceptions of PNES care.
PMID- 25128686
TI - A predictive risk model for medical intractability in epilepsy.
AB - OBJECTIVE: This study aimed to investigate early predictors (6 months after
diagnosis) of medical intractability in epilepsy. METHODS: All children <12 years
of age having two or more unprovoked seizures 24 h apart at Xinhua Hospital
between 1992 and 2006 were included. Medical intractability was defined as
failure, due to lack of seizure control, of more than 2 antiepileptic drugs at
maximum tolerated doses, with an average of more than 1 seizure per month for 24
months and no more than 3 consecutive months of seizure freedom during this
interval. Univariate and multivariate logistic regression models were performed
to determine the risk factors for developing medical intractability. Receiver
operating characteristic curve was applied to fit the best compounded predictive
model. RESULTS: A total of 649 patients were identified, out of which 119 (18%)
met the study definition of intractable epilepsy at 2 years after diagnosis, and
the rate of intractable epilepsy in patients with idiopathic syndromes was 12%.
Multivariate logistic regression analysis revealed that neurodevelopmental delay,
symptomatic etiology, partial seizures, and more than 10 seizures before
diagnosis were significant and independent risk factors for intractable epilepsy.
The best model to predict medical intractability in epilepsy comprised
neurological physical abnormality, age at onset of epilepsy under 1 year, more
than 10 seizures before diagnosis, and partial epilepsy, and the area under
receiver operating characteristic curve was 0.7797. This model also fitted best
in patients with idiopathic syndromes. CONCLUSION: A predictive model of
medically intractable epilepsy composed of only four characteristics is
established. This model is comparatively accurate and simple to apply clinically.
PMID- 25128687
TI - Constitutional chromoanasynthesis: description of a rare chromosomal event in a
patient.
AB - Structural alterations in chromosomes are a frequent cause of cancers and
congenital diseases. Recently, the phenomenon of chromosome crisis, consisting of
a set of tens to hundreds of clustered genomic rearrangements, localized in one
or a few chromosomes, was described in cancer cells under the term
chromothripsis. Better knowledge and recognition of this catastrophic chromosome
event has brought to light two distinct entities, chromothripsis and
chromoanasynthesis. The complexity of these rearrangements and the original
descriptions in tumor cells initially led to the thought that it was an acquired
anomaly. In fact, a few patients have been reported with constitutional
chromothripsis or chromoanasynthesis. Using microarray we identified a very
complex chromosomal rearrangement in a patient who had a cytogenetically visible
rearrangement of chromosome 18. The rearrangement contained more than 15
breakpoints localized on a single chromosome. Our patient displayed intellectual
disability, behavioral troubles and craniofacial dysmorphism. Interestingly, the
succession of duplications and triplications identified in our patient was not
clustered on a single chromosomal region but spread over the entire chromosome
18. In the light of this new spectrum of chromosomal rearrangements, this report
outlines the main features of these catastrophic events and discusses the
underlying mechanism of the complex chromosomal rearrangement identified in our
patient, which is strongly evocative of a chromoanasynthesis.
PMID- 25128689
TI - Population data of 17 Y-STR loci in Nanyang Han population from Henan Province,
Central China.
PMID- 25128688
TI - Co-administration of the broad-spectrum antiviral, brincidofovir (CMX001), with
smallpox vaccine does not compromise vaccine protection in mice challenged with
ectromelia virus.
AB - Natural orthopoxvirus outbreaks such as vaccinia, cowpox, cattlepox and
buffalopox continue to cause morbidity in the human population. Monkeypox virus
remains a significant agent of morbidity and mortality in Africa. Furthermore,
monkeypox virus's broad host-range and expanding environs make it of particular
concern as an emerging human pathogen. Monkeypox virus and variola virus (the
etiological agent of smallpox) are both potential agents of bioterrorism. The
first line response to orthopoxvirus disease is through vaccination with first
generation and second-generation vaccines, such as Dryvax and ACAM2000. Although
these vaccines provide excellent protection, their widespread use is impeded by
the high level of adverse events associated with vaccination using live,
attenuated virus. It is possible that vaccines could be used in combination with
antiviral drugs to reduce the incidence and severity of vaccine-associated
adverse events, or as a preventive in individuals with uncertain exposure status
or contraindication to vaccination. We have used the intranasal mousepox
(ectromelia) model to evaluate the efficacy of vaccination with Dryvax or
ACAM2000 in conjunction with treatment using the broad spectrum antiviral,
brincidofovir (BCV, CMX001). We found that co-treatment with BCV reduced the
severity of vaccination-associated lesion development. Although the immune
response to vaccination was quantifiably attenuated, vaccination combined with
BCV treatment did not alter the development of full protective immunity, even
when administered two days following ectromelia challenge. Studies with a non
replicating vaccine, ACAM3000 (MVA), confirmed that BCV's mechanism of
attenuating the immune response following vaccination with live virus was, as
expected, by limiting viral replication and not through inhibition of the immune
system. These studies suggest that, in the setting of post-exposure prophylaxis,
co-administration of BCV with vaccination should be considered a first response
to a smallpox emergency in subjects of uncertain exposure status or as a means of
reduction of the incidence and severity of vaccine-associated adverse events.
PMID- 25128690
TI - Identification of body fluid-specific DNA methylation markers for use in forensic
science.
AB - DNA methylation, which occurs at the 5'-position of the cytosine in CpG
dinucleotides, has great potential for forensic identification of body fluids,
because tissue-specific patterns of DNA methylation have been demonstrated, and
DNA is less prone to degradation than proteins or RNA. Previous studies have
reported several body fluid-specific DNA methylation markers, but DNA methylation
differences are sometimes low in saliva and vaginal secretions. Moreover,
specific DNA methylation markers in four types of body fluids (blood, saliva,
semen, and vaginal secretions) have not been investigated with genome-wide
profiling. Here, we investigated novel DNA methylation markers for identification
of body fluids for use in forensic science using the Illumina HumanMethylation
450K bead array, which contains over 450,000 CpG sites. Using methylome data from
16 samples of blood, saliva, semen, and vaginal secretions, we first selected
2986 hypermethylated or hypomethylated regions that were specific for each type
of body fluid. We then selected eight CpG sites as novel, forensically relevant
DNA methylation markers: cg06379435 and cg08792630 for blood, cg26107890 and
cg20691722 for saliva, cg23521140 and cg17610929 for semen, and cg01774894 and
cg14991487 for vaginal secretions. These eight selected markers were evaluated in
80 body fluid samples using pyrosequencing, and all showed high sensitivity and
specificity for identification of the target body fluid. We suggest that these
eight DNA methylation markers may be good candidates for developing an effective
molecular assay for identification of body fluids in forensic science.
PMID- 25128691
TI - High isolation rates of multidrug-resistant bacteria from water and carpets of
mosques.
AB - OBJECTIVE: There is little information regarding the isolation of antimicrobial
resistant potentially pathogenic bacteria from water and carpets of mosques
worldwide. The objective of the present investigation is to determine the
bacteriological quality of water and carpets of mosques in Elkhomes city in
Libya. METHODS: Potentially pathogenic bacteria were isolated from water samples
(n=44) and dust samples from carpets (n=50) of 50 mosques in Elkhomes city,
Libya, using standard bacteriological procedures. Susceptibility of isolated
bacteria to antimicrobial agents was determined by the disc-diffusion method.
RESULTS: Of the water samples examined, 12 (27.3%) were positive for Escherichia
coli, 10 (22.7%) for Klebsiella spp., and 15 (34.1%) for other enteric bacteria.
Of the dust samples of carpets examined, 6 (12%) were positive for E. coli, 33
(66%) for Klebsiella spp., and 30 (60%) for Staphylococcus spp. Multidrug
resistance (MDR, resistance to three or more antimicrobial groups) was found
among 48.7% (19/37) and 46.9% (30/64) of the examined enterobacteria from water
and carpets, respectively, and among 66.7% (20/30) of Staphylococcus spp. from
carpets. In addition, methicillin-resistant Staphylococcus aureus (MRSA) was
isolated from a carpet of one mosque. CONCLUSION: Presence of multidrug-resistant
potentially pathogenic bacteria in examined water and carpets indicate that
mosques as communal environments may play a role in the spread of multidrug
resistant bacteria in the community and pose a serious health risk to worshipers.
PMID- 25128692
TI - NAD-dependent ADP-ribosylation of the human antimicrobial and immune-modulatory
peptide LL-37 by ADP-ribosyltransferase-1.
AB - LL-37 is a cationic peptide belonging to the cathelicidin family that has
antimicrobial and immune-modulatory properties. Here we show that the mammalian
mono-ADP-ribosyltransferase-1 (ART1), which selectively transfers the ADP-ribose
moiety from NAD to arginine residues, ADP-ribosylates LL-37 in vitro. The
incorporation of ADP-ribose was first observed by Western blot analysis and then
confirmed by MALDI-TOF. Mass-spectrometry showed that up to four of the five
arginine residues present in LL-37 could be ADP-ribosylated on the same peptide
when incubated at a high NAD concentration in the presence of ART1. The
attachment of negatively charged ADP-ribose moieties considerably alters the
positive charge of the arginine residues thus reducing the cationicity of LL-37.
The cationic nature of LL-37 is key for its ability to interact with cell
membranes or negatively charged biomolecules, such as DNA, RNA, F-actin and
glycosaminoglycans. Thus, the ADP-ribosylation of LL-37 is expected to have the
potential to modulate LL-37 biological activities in several physiological and
pathological settings.
PMID- 25128693
TI - Vascular endothelial function and blood pressure regulation in afferent autonomic
failure.
AB - BACKGROUND: Familial dysautonomia (FD) is a rare hereditary disease characterized
by loss of afferent autonomic neural fiber signaling and consequent profound
impairment of arterial baroreflex function and blood pressure regulation. Whether
vascular endothelial dysfunction contributes to defective vasomotor control in
this form of afferent autonomic failure is not known. METHODS: We assessed blood
pressure response to orthostatic stress and vascular endothelial function with
brachial artery reactivity testing in 34 FD subjects with afferent autonomic
failure and 34 healthy control subjects. RESULTS: Forty-four percent of the
afferent autonomic failure subjects had uncontrolled hypertension at supine rest
(median systolic blood pressure = 148mm Hg, interquartile range (IQR) = 144-155mm
Hg; median diastolic blood pressure = 83mm Hg, IQR = 78-105mm Hg), and 88% had
abnormal response to orthostatic stress (median decrease in systolic blood
pressure after upright tilt = 48mm Hg, IQR = 29-61mm Hg). Flow-mediated brachial
artery reactivity did not differ in subjects with afferent autonomic failure vs.
healthy control subjects (median = 6.00%, IQR = 1.86-11.77%; vs. median = 6.27%,
IQR = 4.65-9.34%; P = 0.75). In afferent autonomic failure subjects, brachial
artery reactivity was not associated with resting blood pressure or the magnitude
of orthostatic hypotension but was decreased in association with reduced
glomerular filtration rate (r = 0.62; P < 0.001). CONCLUSIONS: Brachial artery
reactivity was preserved in subjects with afferent autonomic failure despite the
presence of marked blood pressure dysregulation. Comorbid renal dysfunction was
associated with reduced brachial artery reactivity.
PMID- 25128694
TI - Cardiovascular morbidity and mortality after treatment for ductal carcinoma in
situ of the breast.
AB - BACKGROUND: Recent concerns about potential overdiagnosis and overtreatment of
ductal carcinoma in situ of the breast (DCIS) render evaluation of late effects
of treatment, such as cardiovascular disease (CVD), of great importance. We
studied cardiovascular morbidity and mortality in a large population-based cohort
of DCIS patients. METHODS: Data on all incident DCIS case patients in the
Netherlands between 1989 and 2004 who were diagnosed before the age of 75 years
were obtained (n = 10468). CVD data was acquired through linkage with population
based registries. Standardized mortality ratios were calculated by comparing
mortality in our cohort with that in the Dutch female population, taking into
account person-years of observation. Within-cohort comparisons were based on
multivariable competing-risk regression. RESULTS: Compared with the general
population, 5-year survivors of DCIS had a similar risk of dying due to any cause
(standardized mortality ratio [SMR] = 1.04; 95% confidence interval [CI] = 0.97
to 1.11) but a lower risk of dying of CVD (SMR = 0.77; 95% CI = 0.67 to 0.89). No
difference in CVD risk was found when comparing 5-year survivors treated with
radiotherapy with those treated with surgery only. Left-sided vs right-sided
radiotherapy also did not increase this risk (hazard ratio [HR] = 0.94; 95% CI =
0.67 to 1.32). In a subgroup analysis of all DCIS patients diagnosed between 1997
and 2005, we were able to account for history of CVD and did not observe a risk
difference between treatment groups (left-sided vs right-sided radiotherapy: HR =
0.94; 95% CI = 0.68 to 1.29). CONCLUSIONS: After a median follow-up of 10 years,
we did not find an increased risk for cardiovascular morbidity or mortality after
radiotherapy for DCIS when comparing surgery and radiotherapy vs surgery only,
nor when comparing radiotherapy for left-sided vs right-sided DCIS. Compared with
the general population, DCIS patients have a decreased risk of cardiovascular
death, independent of treatment.
PMID- 25128696
TI - Getting to the heart of the matter.
PMID- 25128697
TI - Natural populations of Spodoptera exigua are infected by multiple viruses that
are transmitted to their offspring.
AB - Sublethal infections by baculoviruses (Baculoviridae) are believed to be common
in Lepidoptera, including Spodoptera exigua. In addition, novel RNA viruses of
the family Iflaviridae have been recently identified in a laboratory population
of S. exigua (S. exigua iflavirus-1: SeIV-1; S. exigua iflavirus-2: SeIV-2) that
showed no overt signs of disease. We determined the prevalence of these viruses
in wild populations and the prevalence of co-infection by the different viruses
in shared hosts. Infection by S. exigua multiple nucleopolyhedrovirus (SeMNPV)
and iflaviruses in S. exigua adults (N=130) from horticultural greenhouses in
southern Spain was determined using qPCR and RT-PCR based techniques
respectively. The offspring of these insects (N=200) was reared under laboratory
conditions and analyzed to determine virus transmission. Overall, 54% of field
caught adults were infected by SeMNPV, 13.1% were infected by SeIV-1 and 7.7%
were infected by SeIV-2. Multiple infections were also detected, with 8.4% of
individuals harboring SeMNPV and one of the iflaviruses, whereas 2.3% of adults
were infected by all three viruses. All the viruses were transmitted to offspring
independently of whether the parental female harbored covert infections or not.
Analysis of laboratory-reared insects in the adult stage revealed that SeIV-1 was
significantly more prevalent than SeMNPV or SeIV-2, suggesting high
transmissibility of SeIV-1. Mixed infection involving three viruses was
identified in 6.5% of laboratory-reared offspring. We conclude that interspecific
interactions between these viruses in co-infected individuals are to be likely
frequent, both in the field, following applications of SeMNPV-based insecticides,
or in laboratory colonies used for SeMNPV mass production.
PMID- 25128695
TI - Hyperthermia inhibits recombination repair of gemcitabine-stalled replication
forks.
AB - BACKGROUND: Gemcitabine is a potent nucleoside analogue against solid tumors, but
development of drug resistance is a substantial problem. Removal of gemcitabine
incorporated into DNA by repair mechanisms may contribute to resistance in chemo
refractory solid tumors. Human hepatocellular carcinoma (HCC) is usually very
chemoresistant to gemcitabine. METHODS: We treated HCC in vitro and in vivo
(orthotopic murine model with human Hep3B or HepG2 xenografts, 7-10 CB17SCID mice
per group) with gemcitabine. The role of homologous recombination repair proteins
in repairing stalled replication forks was evaluated with hyperthermia exposure
and cell-cycle analysis. The Student t-test was used for two-sample comparisons.
Multiple group data were analyzed using one-way analysis of variance. All
statistical tests were two-sided. RESULTS: We demonstrated that Mre11-mediated
homologous recombination repair of gemcitabine-stalled replication forks is
crucial to survival of HCC cells. Furthermore, we demonstrated inhibition of
Mre11 by an exonuclease inhibitor or concomitant hyperthermia. In orthotopic
murine models of chemoresistant HCC, the Hep3B tumor mass with radiofrequency
plus gemcitabine treatment (mean +/- SD, 180+/-91mg) was statistically
significantly smaller compared with gemcitabine alone (661+/-419mg, P = .0063).
CONCLUSIONS: This study provides mechanistic understanding of homologous
recombination inhibiting-strategies, such as noninvasive radiofrequency field
induced hyperthermia, to overcome resistance to gemcitabine in refractory human
solid tumors.
PMID- 25128698
TI - Effect of gamma-cyclodextrin on solubilization and complexation of irbesartan:
influence of pH and excipients.
AB - In effort to prepare an eye drop formulation of irbesartan, the effect of gamma
cyclodextrin complexation on irbesartan solubilization in aqueous solutions was
investigated. The optimum cyclodextrin concentration for formation of
irbesartan/cyclodextrin inclusion complex was found to be 10% (w/v) and the
solubility of ionized irbesartan/gamma-cyclodextrin complex (at pH 7.2) was shown
to be three fold greater than that of the unionized complex (at pH 4.3). The
irbesartan flux through semipermeable membranes increased with increasing gamma
cyclodextrin concentration at both pH values. However, the ionized complex
displayed decrease in the drug permeation coefficient with increasing
cyclodextrin concentration. The effect of four pharmaceutical excipients on the
cyclodextrin solubilization was investigated. EDTA, hydroxypropyl
methylcellulose, and tyloxapol increased complexation efficiency of gamma
cyclodextrin while benzalkonium chloride had negligible effect. The largest
solubilization was observed in the eye drop vehicle that contained all four
excipients in addition to gamma-cyclodextrin. Dynamic light scattering
measurements disclosed that excipients had impact on size of complex aggregates
and consequently on the drug flux through the semipermeable membranes. Complex of
irbesartan/gamma-cyclodextrin was characterized by FT-IR, (1)H NMR, XRPD, and TEM
techniques.
PMID- 25128699
TI - Impaired Src signaling and post-synaptic actin polymerization in Alzheimer's
disease mice hippocampus--linking NMDA receptors and the reelin pathway.
AB - Early cognitive deficits in Alzheimer's disease (AD) have been related to
deregulation of N-methyl-d-aspartate receptors (NMDARs) and synaptic dysfunction
in response to amyloid-beta peptide. NMDAR anchorage to post-synaptic membrane
depends in part on Src kinase, which is also implicated in NMDAR activation and
actin cytoskeleton stabilization, two processes relevant for normal synaptic
function. In this study we analyzed the changes in GluN2B subunit phosphorylation
and the levels of proteins involved in Src related signaling pathways linking the
Tyr kinase to actin cytoskeleton polymerization, namely reelin, disabled-1 (Dab1)
and cortactin, in hippocampal and cortical homogenates obtained from the triple
transgenic mouse model of AD (3xTg-AD) that shows progression of pathology as a
function of age versus age-matched wild-type mice. Moreover, we evaluated
regional post-synaptic actin polymerization using phalloidin labeling in
hippocampal slices. Young (3month-old) 3xTg-AD male mice hippocampus exhibited
decreased GluN2B Tyr1472 phosphorylation and reduced Src activity. In the cortex,
decreased Src activity correlated with reduced levels of reelin and Dab1,
implicating changes in the reelin pathway. We also observed diminished
phosphorylated Dab1 and cortactin protein levels in the hippocampus and cortex of
young 3xTg-AD male mice. Concordantly with the recognized role of these proteins
in actin stabilization, we detected a significant decrease in post-synaptic F
actin in 3month-old 3xTg-AD male CA1 and CA3 hippocampal regions. These data
suggest deregulated Src-dependent signaling pathways involving GluN2B-composed
NMDARs and post-synaptic actin cytoskeleton depolymerization in the hippocampus
in early stages of AD.
PMID- 25128700
TI - Methoxetamine--a novel recreational drug with potent hallucinogenic properties.
AB - Methoxetamine is one of the constantly growing group of novel psychoactive
substances that has emerged in recent years. The compound belongs to the
arylcyclohexylamine class, which is used for its recreational and psychedelic
effects. Methoxetamine is a structural analogue of ketamine, with a much longer
duration of action and intensity of effects, and has been extensively advertised
as its 'legal' and 'bladder friendly' alternative. This review surveys the
current state of knowledge regarding the metabolism, pharmacology, prevalence and
pattern of methoxetamine use, and analytical methods of its detection.
Consumption of methoxetamine bears a significant health risk and may even lead to
fatal intoxication. A significant amount of research is still needed in order to
fully quantify the short- and long-term effects of methoxetamine and its
interaction with other drugs of abuse.
PMID- 25128701
TI - Actions of methyl-, propyl- and butylparaben on estrogen receptor-alpha and -beta
and the progesterone receptor in MCF-7 cancer cells and non-cancerous MCF-10A
cells.
AB - Numerous studies have shown that widely used parabens possess estrogenic
properties. In the present study, we examined the effects of methyl-, propyl- and
butylparaben on the mRNA and protein expression of estrogen receptor (ER)-alpha
(ESR1) and -beta (ESR2) and the progesterone receptor (PGR). Human MCF-7 breast
cancer cells and MCF-10A non-transformed breast epithelial cells were exposed to
parabens at a concentration of 20nM; 17beta-estradiol at a concentration of 10nM,
was used as a positive control. Both propyl- and butylparaben stimulated PGR mRNA
expression in MCF-7 cells, whereas methyl- and propylparaben PGR protein
expression. In MCF-10A cells, butyl- and propylparaben increased only PGR mRNA
expression. All parabens increased ESR1 gene and protein expression in MCF-7 and
with the exception of butylparaben in MCF-10A cells. All parabens significantly
increased ESR2 mRNA and protein expression in MCF-7 cells, but in MCF-10A cells
only ESR2 protein expression. In summary, by virtue of their stimulatory action
on the expression of ESR1, ESR2 and PGR in cancer cells, parabens can be viewed
as potential contributors to breast cancer progression. Extension, the actions of
these parabens on the expression of ERs and PGR in non-cancerous cells point to
possible actions on breast cancer initiation.
PMID- 25128702
TI - Long-term effect of mass chemotherapy, transmission and risk factors for
Schistosoma mansoni infection in very low endemic communities of Venezuela.
AB - The prevalence of Schistosoma mansoni infection in Venezuela has changed from
high to low due mostly to successful control activities, including mass
chemotherapy and molluscicide applications. This study examined the impact of
mass chemotherapy on S. mansoni transmission and risk factors for infection 12
years after administration of praziquantel in Venezuela. Two relatively isolated
rural communities were studied, one with snail control (Manuare) and the second
without (Los Naranjos). A cross-sectional survey of randomly selected households
included 226 (Manuare) and 192 (Los Naranjos) consenting participants. S. mansoni
prevalence was determined using a combination of coprological (Kato-Katz) and
serological (circumoval precipitin test, alkaline phosphatase immunoassay and
Western blot) tests. Data on epidemiological and socioeconomic risk factors were
obtained through individual structured interviews. Univariate analysis and
multivariate logistic regression models identified independent risk factors for
infection. Water sites were examined for the presence of Biomphalaria glabrata
snails. Only one participant was positive by coprology. The overall prevalences
according to the combined tests were 32.7% in Manuare and 26.6% in Los Naranjos.
Lower prevalences (12.7% in Manuare and 13.2% in Los Naranjos) were found in
children <12 years of age representing those born after mass chemotherapy. Social
demographic variables associated with infection in both communities were older
age (>25 years), contact with specific water sites, and being a farmer/non
specialised worker. Mass treatment with praziquantel applied once to endemic
communities led to an important and long-lasting sustained reduction of S.
mansoni infections independent of the application of snail control. A degree of
low active transmission of S. mansoni persisted in the treated areas which was
associated with similar factors in both communities.
PMID- 25128703
TI - An ultra-sensitive assay targeting the circulating anodic antigen for the
diagnosis of Schistosoma japonicum in a low-endemic area, People's Republic of
China.
AB - The downward trend in prevalence and intensity of Schistosoma japonicum infection
in the People's Republic of China (P.R. China) has reached a level where accurate
methods are required for monitoring the national schistosomiasis control
programme and to verify whether transmission has been interrupted. We have
assessed the prevalence of active S. japonicum infection by use of an up
converting phosphor lateral-flow (UCP-LF) assay for determination of circulating
anodic antigens (CAA) in urine and serum, and compared the findings with those of
the Kato-Katz technique for egg detection in stool and an immunohaemagglutination
assay (IHA) for specific antibodies in serum. The study was carried out in three
villages located in a remaining S. japonicum-endemic area in P.R. China. Overall,
423 individuals were investigated by Kato-Katz, 395 by IHA, 371 with the UCP-LF
CAA assay adapted for urine and 178 with the UCP-LF CAA assay applied on serum.
The IHA showed the highest number of positive results (n=107, 27.1%). The UCP-LF
CAA urine assay detected 36 CAA positives (9.7%) and the serum-based CAA assay 21
positives (11.8%). The Kato-Katz technique revealed only six positive stool
samples (1.4%). Among those 166 individuals with complete data records,
sensitivities of the different assays were determined versus a combined 'gold'
standard, showing the highest sensitivity for the urine CAA assay (93%), followed
by the serum CAA (73%) and IHA (53%), whilst triplicate Kato-Katz thick smears
had a very low sensitivity (13%). Serum CAA concentrations were about 10-fold
higher than in urine and were significantly correlated. Highest prevalences as
determined by CAA were found in older age groups (>40 years). Half of the CAA- or
egg-positive cases were negative for antibodies by IHA, thereby revealing an
important obstacle for the effectiveness of the current schistosomiasis control
and elimination efforts. The significantly higher prevalence of active
schistosome infections as shown by the urine and serum UCP-LF CAA assays has
implications for the national control and elimination programme in P.R. China,
particularly in respect to case-finding and intervention strategies.
PMID- 25128704
TI - Concomitant inhibition of primary equine bronchial fibroblast proliferation and
differentiation by selective beta2-adrenoceptor agonists and dexamethasone.
AB - Altered airway cell proliferation plays an important role in the pathogenesis of
human bronchial asthma and chronic obstructive pulmonary disease (COPD) as well
as the equine recurrent airway obstruction (RAO) with consistent changes, i.e.
narrowing the airway wall, explained by proliferation and differentiation of
fibroblasts. In permanent cell lines, it has been suggested that beta2
adrenoceptor agonists and glucocorticoids regulate cell proliferation via the
beta2-adrenoceptor pathway; indeed, no study was carried out in fresh isolated
primary equine bronchial fibroblasts (EBF). We characterized the beta
adrenoceptors in EBF, and compared effects of long-acting (clenbuterol) and short
acting (salbutamol and isoproterenol) beta2-agonists and dexamethasone on
proliferation, differentiation and collagen synthesis. High density (Bmax; 5037+/
494 sites/cell) of beta2-adrenoceptor subtype was expressed in EBF. beta2
agonists inhibited concentration-dependently EBF proliferation with potency of
clenbuterol>salbutamol "isoproterenol which was inhibited by ICI 118.551 and
propranolol but not by CGP 20712A. In contrast, dexamethasone alone inhibited
less EBF proliferation, but the effect was high when dexamethasone was combined
with beta2-agonists. Transforming growth factor-beta1 (TGF-beta1) increased
transformation of fibroblasts into myofibroblasts, which was inhibited by
clenbuterol and dexamethasone alone and drug combination resulted in high
inhibition rate. Collagen synthesis in EBF was rather hampered by dexamethasone
than by beta-agonists. Collectively, the expression of beta2-adrenoceptor subtype
in EBF and the anti-proliferative effect of clenbuterol suggest that beta2
adrenoceptors are growth inhibitory and anti-fibrotic in EBF. These beta2-agonist
effects in EBF were synergistically enhanced by dexamethasone, providing the
additive effects of glucocorticoids to counteract airway remodelling and
morbidity of asthma and RAO.
PMID- 25128706
TI - Regulation of oxidative stress-induced cytotoxic processes of citrinin in the
fission yeast Schizosaccharomyces pombe.
AB - In this study, the citrinin (CTN)-induced accumulation of reactive oxygen species
(ROS) and the regulation of the activities of antioxidant enzymes were
investigated in acute toxicity tests in Schizosaccharomyces pombe. 30% of the CTN
was accumulated by the cells in 1000 MUM CTN solution. In comparison with the
control, exposure of 10(7) cells ml(-1) to 1000 MUM CTN for 60 min at pH = 4.5
induced significantly (p < 1%) elevated levels of peroxides and total ROS, but
not of superoxide or hydroxyl radicals, while there was a 3-fold increase in the
concentration of glutathione. ROS-induced adaptation processes at cell and
molecular levels via activation of the redox-sensitive transcription factors Pap1
and (in part) Atf1 resulted in significantly increased specific activities of
glutathione peroxidases, glucose-6-phosphate dehydrogenase and glutathione S
transferase and in decreased levels of catalase and glutathione reductase, but no
changes were detected in the activities of superoxide dismutases. This treatment
caused a G2/M cell cycle arrest and elevated the number of fragmented nuclei,
which is one of the markers of apoptosis. Comparison of these results with those
for the positive control, 200 MUM H2O2, suggested that CTN induced a medium level
of oxidative stress.
PMID- 25128705
TI - Effects of interfering RNA of alpha-1,3-galactosyltransferase and nuclear factor
kappa B on cardiac xenotransplantation.
AB - BACKGROUND: Both alpha1,3-galactosyltransferase (alpha1,3GT) and nuclear factor
kappa B (NF-kappaB) play an important role in the immune response of
xenotransplantation. The purpose of this study is to investigate the effect of
RNAi of alpha1,3GT and NF-kappaB on xenotransplantation. METHODS: Lentiviral
vectors with shRNA focusing on alpha1, 3GT and RelA were constructed. The effect
of RNAi on alpha1, 3GT and RelA was examined in vitro and in vivo. Additionally,
we established a mouse-to-rat heterotopic cardiac xenotransplantatic model (donor
hearts transplanted to the right side of the neck in rat) using a modified cuff
technique. The survival time of donor hearts in each group was monitored. The
expressions of alpha1, 3GT and RelA mRNA, Galalpha1,3Gal antigen, and RelA
protein were detected by RT-PCR, immunofluorescence, and Western blot
respectively. The expressions of C3, IgM, IgG, NK, macrophages, ICAM-1 on donor
hearts were examined by immunohistochemistry. RESULTS: High titer lentiviral
vectors carrying alpha1, 3GT and RelA shRNA plasmids had a high and stable
transfection rate on EOMA in vitro. In vivo, heart tissue showed a much stronger
GFP expression and significant decrease in target gene mRNA expression and
protein expression in shRNA interfering groups (p < 0.01). The survival time of
alpha1,3GTi-3 and dual lentiviral vector groups was significantly longer than
other groups. The mRNA expression levels of alpha1,3GT and RelA, as well as
Galalpha(1,3)Gal and RelA proteins, in alpha1,3GTi-3, RelAi-3, and dual
lentiviral vector groups were downregulated and compared to other groups (p <
0.01). The depositions of C3, IgM, IgG in alpha1,3GTi-3 group and dual lentiviral
vector group were less than other groups (p < 0.01). The infiltration of NK,
macrophages and ICAM-1 in alpha1,3GTi-3 group and dual lentiviral vector group
was more than other groups (p < 0.01), but the infiltration of NK, macrophages
and ICAM-1 in dual lentiviral vector group was less than alpha1,3GTi-3 group (p <
0.01). CONCLUSIONS: Our results indicate that RNAi technology with lentiviral
vectors is an effective method to transmit exogenous genes into living bodies and
stably inhibit the expression of target genes. Moreover, siRNA targeting the
alpha1,3GT gene was found to control the immune process and obviously prolong the
survival time of donors, whereas knocking down NF-kappaB alone showed no
differences. However, the RNAi of NF-kappaB can make the infiltration of
macrophages and natural killer cells decrease, and the expression of ICAM-1 in
the xenografts also decreases, contributing to the restraining of AVR.
PMID- 25128707
TI - Differential activation of MAPKs by individual and combined ochratoxin A and
citrinin treatments in porcine kidney PK15 cells.
AB - The aim of this study was to investigate the underlying mechanisms of OTA and CTN
individual and combined toxicity in porcine kidney PK15 cells of proximal tubule
origin. Activation and expression of mitogen-activated protein kinases (MAPKs)
ERK, JNK and p38 were determined by Western blot analysis. MAPKs were
differentially activated by single or dual OTA and CTN treatments. Single OTA and
CTN stimulated transient ERK and prolonged JNK activation, while phospho-p38
signal was more persistent after OTA treatment. Mycotoxin mixture provoked
significant down-regulation of ERK activation, more prolonged phospho-p38 signal,
and two-stage JNK phosphorylation pattern. In order to define the role of
particular MAPKs in mycotoxin(s) cytotoxicity, we performed MTT assay with
specific MAPKs inhibitors. In both individual and combined treatments JNK and p38
inhibition significantly induced cell survival. When cells were exposed to toxin
mixture, inhibition of ERK also promoted cell survival, although to a lesser
extent that JNK and p38 inhibition. Next we investigated the association between
calcium (Ca(2+)) and MAPKs after OTA and/or CTN treatments, and we employed
Ca(2+) chelator BAPTA-AM. We demonstrated that p38 activation was significantly
down-regulated in cells treated with CTN alone or OTA + CTN suggesting the role
of Ca(2+) in mycotoxin-induced cell death.
PMID- 25128708
TI - An alternative micromethod to access the procoagulant activity of Bothrops
jararaca venom and the efficacy of antivenom.
AB - The assessment of the capacity of antivenoms to neutralize the lethal activity of
snake venoms still relies largely on traditional rodent lethality assay (LD50).
However, adequately validated in vitro tests should be introduced for assessing
antivenom neutralizing capacity in plasma of immunized horses as well as for in
process quality control. The dynamic of fibrin formation in recalcified avian
plasma samples is extremely slow, when compared to that presented by mammalian
plasmas. In this study, we present one new coagulant assay, by performing dose
response curve after plotting the clotting time (CT) parameter of the ROTEM
profile of recalcified chicken plasma samples (target) against semi-logarithmic
doses of Bothrops jararaca venom (agonist), either in absence or in presence of
the semi-logarithmic doses of anti-bothropic serum (ABS) (antagonist). The mean
coagulant dose 50% (CD50) was defined as the quantity of venom (in MUg) which
reduces CT to 900 s, between minimum and maximum responses. The CT induced by
5CD50 of the venom was used as the control for calculating the effective dose
(ED) of each batch of ABS. ED was defined as the ABS dose (nanoliters, nL) at
which CT induced by one amount of venom corresponding to 5CD50 is displaced to
the maximum threshold (1800 s). Five batches of the ABS, previously assayed for
their lethality neutralizing activity (ED50) were assayed. The correlation
coefficient (r) between both in vitro (ED) and in vivo (ED50) values was 0.87 (p
value < 0.05). We propose this micro method as highly sensitive for
characterization and quantification of possible procoagulant activity of small
doses of snake venoms (nanograms) and for detecting small doses (nanoliters) of
specific antibodies against this effect in little volume samples of biological
fluids.
PMID- 25128709
TI - Improving diffusion-weighted imaging of post-mortem human brains: SSFP at 7 T.
AB - Post-mortem diffusion imaging of whole, human brains has potential to provide
data for validation or high-resolution anatomical investigations. Previous work
has demonstrated improvements in data acquired with diffusion-weighted steady
state free precession (DW-SSFP) compared with conventional diffusion-weighted
spin echo at 3T. This is due to the ability of DW-SSFP to overcome signal-to
noise and diffusion contrast losses brought about by tissue fixation related
decreases in T2 and ADC. In this work, data of four post-mortem human brains were
acquired at 3T and 7 T, using DW-SSFP with similar effective b-values
(b(eff)~5150 s/mm(2)) for inter-field strength comparisons; in addition, DW-SSFP
data were acquired at 7 T with higher b(eff) (~8550 s/mm(2)) for intra-field
strength comparisons. Results demonstrate that both datasets acquired at 7 T had
higher SNR and diffusion contrast than data acquired at 3T, and data acquired at
higher b(eff) had improved diffusion contrast than at lower b(eff) at 7 T. These
results translate to improved estimates of secondary fiber orientations leading
to higher fidelity tractography results compared with data acquired at 3T.
Specifically, tractography streamlines of cortical projections originating from
the corpus callosum, corticospinal tract, and superior longitudinal fasciculus
were more successful at crossing the centrum semiovale and projected closer to
the cortex. Results suggest that DW-SSFP at 7 T is a preferential method for
acquiring diffusion-weighted data of post-mortem human brain, specifically where
the primary region of interest involves crossing white matter tracts.
PMID- 25128710
TI - The influence of stimulus format on drawing--a functional imaging study of
decision making in portrait drawing.
AB - To copy a natural visual image as a line drawing, visual identification and
extraction of features in the image must be guided by top-down decisions, and is
usually influenced by prior knowledge. In parallel with other behavioral studies
testing the relationship between eye and hand movements when drawing, we report
here a functional brain imaging study in which we compared drawing of faces and
abstract objects: the former can be strongly guided by prior knowledge, the
latter less so. To manipulate the difficulty in extracting features to be drawn,
each original image was presented in four formats including high contrast line
drawings and silhouettes, and as high and low contrast photographic images. We
confirmed the detailed eye-hand interaction measures reported in our other
behavioral studies by using in-scanner eye-tracking and recording of pen
movements with a touch screen. We also show that the brain activation pattern
reflects the changes in presentation formats. In particular, by identifying the
ventral and lateral occipital areas that were more highly activated during
drawing of faces than abstract objects, we found a systematic increase in
differential activation for the face-drawing condition, as the presentation
format made the decisions more challenging. This study therefore supports
theoretical models of how prior knowledge may influence perception in untrained
participants, and lead to experience-driven perceptual modulation by trained
artists.
PMID- 25128711
TI - Emotional speech synchronizes brains across listeners and engages large-scale
dynamic brain networks.
AB - Speech provides a powerful means for sharing emotions. Here we implement novel
intersubject phase synchronization and whole-brain dynamic connectivity measures
to show that networks of brain areas become synchronized across participants who
are listening to emotional episodes in spoken narratives. Twenty participants'
hemodynamic brain activity was measured with functional magnetic resonance
imaging (fMRI) while they listened to 45-s narratives describing unpleasant,
neutral, and pleasant events spoken in neutral voice. After scanning,
participants listened to the narratives again and rated continuously their
feelings of pleasantness-unpleasantness (valence) and of arousal-calmness.
Instantaneous intersubject phase synchronization (ISPS) measures were computed to
derive both multi-subject voxel-wise similarity measures of hemodynamic activity
and inter-area functional dynamic connectivity (seed-based phase synchronization,
SBPS). Valence and arousal time series were subsequently used to predict the ISPS
and SBPS time series. High arousal was associated with increased ISPS in the
auditory cortices and in Broca's area, and negative valence was associated with
enhanced ISPS in the thalamus, anterior cingulate, lateral prefrontal, and
orbitofrontal cortices. Negative valence affected functional connectivity of
fronto-parietal, limbic (insula, cingulum) and fronto-opercular circuitries, and
positive arousal affected the connectivity of the striatum, amygdala, thalamus,
cerebellum, and dorsal frontal cortex. Positive valence and negative arousal had
markedly smaller effects. We propose that high arousal synchronizes the
listeners' sound-processing and speech-comprehension networks, whereas negative
valence synchronizes circuitries supporting emotional and self-referential
processing.
PMID- 25128712
TI - Circadian modulation of motor-related beta oscillatory responses.
AB - Previous electrophysiological investigations have evaluated movement-related beta
(14-28 Hz) oscillatory activity in healthy participants. These studies have
described an abrupt decrease in beta activity that starts before movement onset,
and a sharp increase in beta power that peaks after movement termination. These
neural responses have been respectively termed the event-related beta
desynchronization or pre-movement beta ERD, and the post-movement beta rebound
(PMBR). Previous studies have shown that a variety of movement parameters and
demographic factors (e.g., age) modulate the amplitude of these oscillatory
responses, and in the current study we evaluated whether the amplitudes follow a
biological temporal rhythm (e.g., circadian), as it is known that spontaneous
beta levels increase from morning to afternoon in some brain areas. To this end,
we used magnetoencephalography (MEG) to evaluate oscillatory activity during a
right hand finger-tapping task in four participants who were recorded at three
different times (09:00, 12:00, 16:00) on three consecutive days (i.e., 36 total
MEG sessions). All MEG data were corrected for head motion and examined in the
time-frequency domain using beamforming methods. We found a significant linear
increase in beta ERD amplitude from 09:00 to 16:00 h in the left precentral
gyrus, left premotor cortices, left supplementary motor area (SMA), and right
precentral and postcentral gyri. In contrast, the amplitude of the PMBR was very
steady across the day in all brain regions except the left SMA, which exhibited a
linear increase from morning to afternoon. Finally, beta levels during the
baseline period also increased from 09:00 to 16:00 in most regions of the
cortical sensorimotor network. These data show that both the pre-movement beta
ERD and spontaneous beta levels strongly increase from morning to afternoon in
the motor cortices, which may indicate that the amplitude of the beta ERD
response is determined by the spontaneous beta level during the motor planning
period.
PMID- 25128714
TI - New cholesterol guidelines and the secondary prevention of cardiovascular disease
- a commentary on epistemic aspects.
AB - The recommendations contained in the 2013 cholesterol guidelines may be described
as either with or without a direct empirical clinical trial basis.
Recommendations without a direct empirical clinical trial basis tend to be
controversial. Recommendations with and without a direct empirical clinical trial
basis are mixed in the same text - while at the same time (rightfully) rejecting
previous recommendations, also without a direct empirical clinical trial basis.
PMID- 25128713
TI - Age-associated changes in rat immune system: lessons learned from experimental
autoimmune encephalomyelitis.
AB - Aging is associated with the decline in immune response to infectious agents and
tumors and increasing risk of autoimmunity, but the incidence of autoimmune
diseases does not increase in the elderly. To elucidate the cellular and
molecular mechanisms influencing clinical expression of autoimmunity in aged
animals, the phenotypic and functional characteristics of mononuclear cells
isolated from the spinal cords of 3-month-old (young) and 26-month-old (aged)
Dark Agouti rats immunized to induce experimental autoimmune encephalomyelitis
(EAE) - the model of multiple sclerosis, the most common autoimmune disease of
the central nervous system, were examined. Aged rats were less susceptible to EAE
induction, and the neurological and histological picture was milder in those rats
which developed the clinically manifested disease. At the peak of the disease,
several times fewer mononuclear cells and T lymphocytes were isolated from the
spinal cords of aged rats compared with the young ones. The frequency of CD4+
cells among TCRalphabeta+ lymphocytes, as well as that of reactivated
CD134(OX40)+ cells within its CD4+ T-lymphocyte subpopulation, was less in spinal
cords of aged compared with young rats. Additionally, CD134 surface density on
CD4+ lymphocytes was decreased in the spinal cord of aged rats. The changes in
CD134 expression most likely reflected in part age-related intrinsic changes in
CD4+ lymphocytes as the expression of this molecule was also impaired on in vitro
stimulated naive CD4+ splenocytes from aged rats compared with young animals. In
addition, greater frequency of CD8+ lymphocytes with regulatory phenotypes could
also contribute to impaired CD4+ cell reactivation in aged rats. The increased
apoptosis of CD4+ cells from aged rats was consistent with their impaired
reactivation and it was accompanied by the greater frequency of
CD4+CD11b+CD45(int/high) cells, which are supposed to be actively engaged in
apoptotic cell phagocytosis and to have immunoregulatory properties. Compared
with young rats, following short-term PMA and ionomycin stimulation in vitro, the
frequency of IL-17+ and IFN-gamma+CD4+ T lymphocytes among the spinal cord
mononuclear cells from aged rats and the cytokine expression density on a per
lymphocyte basis were reduced. Additionally, the increase in the proportion of
autoregulatory IL-17+IL-10+ cells on the account of proinflammatory IL-17+IFN
gamma+ cells within IL-17+ lymphocytes suggested their lower pathogenic capacity
in aged rats. This most likely reflected alterations in the aged rat spinal cord
cytokine milieu, which were mirrored in a diminished expression of IL-1beta mRNA
followed by an enhanced expression of IL-6 and TGF-beta mRNA. Overall, the study
points to age-related changes in T lymphocytes and other cells from the spinal
cord infiltrate which could contribute to the decreased susceptibility of aged
rats to the induction of EAE.
PMID- 25128715
TI - Racial/ethnic disparities in mental health over the first 2 years after traumatic
brain injury: a model systems study.
AB - OBJECTIVE: To determine whether racial/ethnic disparities occur in depression,
anxiety, and satisfaction with life at 1 and 2 years postdischarge. DESIGN: A
prospective, longitudinal, multicenter study of individuals with traumatic brain
injury (TBI) participating in the National Institute on Disability and
Rehabilitation Research Traumatic Brain Injury Model Systems project. Medical,
demographic, and outcome data were obtained from the Model Systems database at
baseline, as well as 1 and 2 years postdischarge. SETTING: A total of 16 TBI
Model Systems hospitals in the United States. PARTICIPANTS: Individuals with
moderate or severe TBI (N=1662) aged 16 years or older consecutively discharged
between January 2008 and June 2011 from acute care and comprehensive inpatient
rehabilitation at a Model Systems hospital. INTERVENTION: Not applicable. MAIN
OUTCOME MEASURES: The Patient Health Questionnaire-9, Generalized Anxiety
Disorder 7-item scale, and Satisfaction with Life Scale assessed depression,
anxiety, and satisfaction with life at 1 and 2-year follow-ups. RESULTS: After
controlling for all possible covariates, hierarchal linear models found that
black individuals had elevated depression across the 2 time points relative to
white individuals. Asian/Pacific Islanders' depression increased over time in
comparison to the decreasing depression in those of Hispanic origin, which was a
greater decrease than in white individuals. Black individuals had lower life
satisfaction than did white and Hispanic individuals, but only marginally greater
anxiety over time than did white individuals and similar levels of anxiety as did
Asian/Pacific Islanders and Hispanic individuals. CONCLUSIONS: Mental health
trajectories of individuals with TBI differed as a function of race/ethnicity
across the first 2 years postdischarge, providing the first longitudinal evidence
of racial/ethnic disparities in mental health after TBI during this time period.
Further research will be required to understand the complex factors underlying
these differences.
PMID- 25128716
TI - Development and initial psychometric evaluation of the Mobility Activities
Measure for Inpatient Rehabilitation Settings (Mobam-in).
AB - OBJECTIVE: To describe the development and the initial psychometric evaluation of
a mobility measure for inpatient postacute rehabilitation settings-the Mobility
Activities Measure for Inpatient Rehabilitation Settings (Mobam-in). DESIGN: Self
report-based psychometric study. SETTING: Postacute rehabilitation unit of a
public hospital. PARTICIPANTS: A consecutive sample of inpatients (N=239)
receiving postacute rehabilitation care. INTERVENTIONS: Not applicable. MAIN
OUTCOME MEASURES: We developed a 30-item mobility measure, using the Mobility
Activities Measure (Mobam) framework, to assess functioning across 5 mobility
activity domains classified within the International Classification of
Functioning, Disability and Health. These were (1) changing and maintaining body
position involving only sitting and/or lying (4 items); (2) changing and
maintaining body position involving standing up (6 items); (3) carrying and
moving objects using the hand and shoulder (6 items); (4) handling objects using
only the hand and/or forearm (7 items); and (5) walking and moving (7 items).
Psychometric analyses were conducted to test assumptions underlying the scaling
and scoring of Mobam-in scales, and to test both the reliability and validity.
RESULTS: Multitrait scaling and confirmatory factor analyses (with Tucker-Lewis
Index median, .99; root mean square error of approximation median, .025)
supported the assumption of unidimensionality concerning each domain. Five
dimensions appeared to be stable across diverse diagnostic groups (the percentage
of items with discriminant validity ranged from 93% to 100%, Cronbach coefficient
ranged from .859 to .966). Rasch model (Masters' partial credit) showed that all
items could be located along a continuum in each dimension, with goodness-of-fit
criteria of infit and outfit mean-square values between 0.6 and 1.4. Test-retest
reliability was excellent (intraclass correlation coefficients median, .98).
Groups with more severe conditions and lower functional independence scored lower
on Mobam-in scales, as hypothesized. CONCLUSIONS: Mobam-in covers 5 dimensions of
mobility activities. The Mobam framework is an effective reference for building
outcome instruments.
PMID- 25128717
TI - Nanoparticle multivalency counterbalances the ligand affinity loss upon
PEGylation.
AB - The conjugation of receptor ligands to shielded nanoparticles is a widely used
strategy to precisely control nanoparticle-cell interactions. However, it is
often overlooked that a ligand's affinity can be severely impaired by its
attachment to the polyethylene glycol (PEG) chains that are frequently used to
protect colloids from serum protein adsorption. Using the model ligand EXP3174, a
small-molecule antagonist for the angiotensin II receptor type 1 (AT1R), we
investigated the ligand's affinity before and after its PEGylation and when
attached to PEGylated nanoparticles. The PEGylated ligand displayed a 580-fold
decreased receptor affinity compared to the native ligand. Due to their
multivalency, the nanoparticles regained a low nanomolar receptor affinity, which
is in the range of the affinity of the native ligand. Moreover, a four orders of
magnitude higher concentration of free ligand was required to displace PEGylated
nanoparticles carrying EXP3174 from the receptor. On average, one nanoparticle
was decorated with 11.2 ligand molecules, which led to a multivalent enhancement
factor of 22.5 compared to the monovalent PEGylated ligand. The targeted
nanoparticles specifically bound the AT1R and showed no interaction to receptor
negative cells. Our study shows that the attachment of a small-molecule ligand to
a PEG chain can severely affect its receptor affinity. Concomitantly, when the
ligand is tethered to nanoparticles, the immense avidity greatly increases the
ligand-receptor interaction. Based on our results, we highly recommend the
affinity testing of receptor ligands before and after PEGylation to identify
potent molecules for active nanoparticle targeting.
PMID- 25128718
TI - Pre-systemic metabolism of orally administered drugs and strategies to overcome
it.
AB - The oral bioavailability of numerous drugs is not only limited by poor solubility
and/or poor membrane permeability as addressed by the biopharmaceutical
classification system (BCS) but also by a pre-systemic metabolism taking place to
a high extent in the intestine. Enzymes responsible for metabolic reactions in
the intestine include cytochromes P450 (CYP450), transferases, peptidases and
proteases. Furthermore, in the gut nucleases, lipases as well as glycosidases
influence the metabolic pathway of drugs and nutrients. A crucial role is also
played by the intestinal microflora able to metabolize a wide broad of
pharmaceutical compounds. Strategies to provide a protective effect towards an
intestinal pre-systemic metabolism are based on the co-administration of enzyme
inhibitor being optimally immobilized on unabsorbable and undegradable polymeric
excipients in order to keep them concentrated there where an inhibitory effect is
needed. Furthermore, certain polymeric excipients such as polyacrylates exhibit
per se enzyme inhibitory properties. In addition, by incorporating drugs in
cyclodextrines, in self-emulsifying drug delivery systems (SEDDS) or liposomes a
protective effect towards an intestinal enzymatic attack can be achieved. Being
aware of the important role of this pre-systemic metabolism by integrating it in
the BCS as third dimension and keeping strategies to overcome this enzymatic
barrier in mind, the therapeutic efficacy of many orally given drugs can
certainly be substantially improved.
PMID- 25128719
TI - Resistin: insulin resistance to malignancy.
AB - Adipose tissue is recognized as an endocrine organ that secretes bioactive
substances known as adipokines. Excess adipose tissue and adipose tissue
dysfunction lead to dysregulated adipokine production that can contribute to the
development of obesity-related co-morbidities. Among the various adipokines,
resistin, which was initially considered as a determinant of the emergence of
insulin resistance in obesity, has appeared as an important link between obesity
and inflammatory processes. Several experimental and clinical studies have
suggested an association between increased resistin levels and severe conditions
associated with obesity such as cardiovascular disease and malignancies. In this
review, we present the growing body of evidence that human resistin is an
inflammatory biomarker and potential mediator of obesity-associated diseases. A
common pathway seems to involve the combined alteration of immune and
inflammatory processes that favor metabolic disturbances, atherosclerosis and
carcinogenesis. The mode of action and the signaling pathways utilized by
resistin in its interactions with target cells could involve oxidative and
nitrosative stress. Therefore, resistin could function as a key molecule in the
complications of obesity development and could potentially be used as a
diagnostic and prognostic marker.
PMID- 25128720
TI - Effect of interference from hemolysis, icterus and lipemia on routine pediatric
clinical chemistry assays.
AB - BACKGROUND: Clinical laboratory assays can be affected by interferents like
hemoglobin (Hb), lipids and bilirubin. We evaluated the effect of these
interferences on pediatric samples for different chemistry assays. Further we
established cut-off indices above which these interferences confound sample
results. METHODS: Three separate serum pools were spiked with increasing
concentrations of hemolysate or intralipid or bilirubin and different analytes
were analyzed. The Hemolysis-(H), Lipemia-(T) and Icterus-(I) indices were
measured on Vitros 5600. Analytes affected by lipemia were treated with LipoClear
(r) and re-analyzed. All the measured analytes were compromised by gross
hemolysis (H-Index >1000). RESULTS: Except lipase and magnesium (Mg(++)), all
other analytes were affected by moderate (H-Index >250) and significant hemolysis
(H-Index >500). Low estradiol levels showed a significant effect at severe
icterus (I-Index >20.0). C3, C4, Ceruloplasmin, Haptoglobin, Immunoglobulins (Ig)
and Vitamin D were significantly affected by moderate (T-Index >100) and severe
(T-Index >500) lipemia. LipoClear (r) treatment significantly attenuated the
lipemic interference on the above analytes except for C3, C4, and IgG.
CONCLUSIONS: Accurate reporting of pediatric samples for the analytes affected by
common interferences will lead to better clinical interpretation.
PMID- 25128721
TI - A computational model for exploratory activity of rats with different anxiety
levels in elevated plus-maze.
AB - The elevated plus-maze is an apparatus widely used to study the level of anxiety
in rodents. The maze is plus-shaped, with two enclosed arms and two open arms,
and elevated 50cm from the floor. During a test, which usually lasts for 5min,
the animal is initially put at the center and is free to move and explore the
entire maze. The level of anxiety is measured by variables such as the percentage
of time spent and the number of entries in the enclosed arms. High percentage of
time spent at and number of entries in the enclosed arms indicate anxiety. Here
we propose a computational model of rat behavior in the elevated plus-maze based
on an artificial neural network trained by a genetic algorithm. The fitness
function of the genetic algorithm is composed of reward (positive) and punishment
(negative) terms, which are incremented as the computational agent (virtual rat)
moves in the maze. The punishment term is modulated by a parameter that simulates
the effects of different drugs. Unlike other computational models, the virtual
rat is built independently of prior known experimental data. The exploratory
behaviors generated by the model for different simulated pharmacological
conditions are in good agreement with data from real rats.
PMID- 25128722
TI - Pixel timing correction in time-lapsed calcium imaging using point scanning
microscopy.
AB - In point scanning imaging, data are acquired by sequentially scanning each pixel
of a predetermined area. This way of scanning leads to time delays between
pixels, especially for lower scanning speed or large scanned areas. Therefore,
experiments are often performed at lower framerates in order to ensure a
sufficient signal-to-noise ratio, even though framerates above 30 frames per
second are technically feasible. For these framerates, we suggest that it becomes
crucial to correct the time delay between image pixels prior to analyses. In this
paper, we apply temporal interpolation (or pixel timing correction) for calcium
imaging in two-photon microscopy as an example of fluorescence imaging. We
present and compare three interpolation methods (linear, Lanczos and cubic B
spline). We test these methods on a simulated network of coupled bursting neurons
at different framerates. In this network, we introduce a time delay to simulate a
scanning by point scanning microscopy. We also assess these methods on actual
microscopic calcium imaging movies recorded at usual framerates. Our numerical
results suggest that point scanning microscopy imaging introduces statistically
significant time delays between image pixels at low frequency. However, we
demonstrate that pixel timing correction compensates for these time delays,
regardless of the used interpolation method.
PMID- 25128723
TI - A technique to measure cold adaptation in freely behaving mice.
AB - BACKGROUND: Adaptation to environmental temperature is essential for survival in
seasonal areas. The mechanisms of adaptation have been studied in vitro, but it
has not been quantified in vivo. NEW METHOD: The extended Cold Plantar Assay
(eCPA) cools the entire testing environment. Once the desired environmental
temperature has been reached, a separate focal cold stimulus is applied to the
hindpaw and the latency to withdrawal is recorded as a proxy for cold
sensitivity. RESULTS: Using this technique, we can test the cold responsiveness
of freely behaving mice at ambient temperatures ranging from 5 degrees C to 30
degrees C. The responses are consistent and unambiguous, and the environmental
temperatures generated are reproducible. We are also able to measure cold
responsiveness as animals are in the process of adapting to cold environments.
COMPARISON WITH EXISTING METHOD(S): Existing methods, such as the dynamic cold
plate and the 2-plate preference assay test how mice respond to cold
environments, but cannot assess how the thresholds for response are changed by
acclimation in cold environments. Additionally, the eCPA requires very little
specialized equipment, can test many mice at the same time on one apparatus, and
has an objective readout. CONCLUSIONS: The extended Cold Plantar assay is a
significant methodological improvement, allowing the assessment of cold
responsiveness in freely behaving mice at a wide range of environmental
temperature conditions and during cold adaptation.
PMID- 25128725
TI - The mitochondrial genome of Frankliniella intonsa: insights into the evolution of
mitochondrial genomes at lower taxonomic levels in Thysanoptera.
AB - Thrips is an ideal group for studying the evolution of mitochondrial (mt) genomes
in the genus and family due to independent rearrangements within this order. The
complete sequence of the mitochondrial DNA (mtDNA) of the flower thrips
Frankliniella intonsa has been completed and annotated in this study. The
circular genome is 15,215bp in length with an A+T content of 75.9% and contains
the typical 37 genes and it has triplicate putative control regions. Nucleotide
composition is A+T biased, and the majority of the protein-coding genes present
opposite CG skew which is reflected by the nucleotide composition, codon and
amino acid usage. Although the known thrips have massive gene rearrangements, it
showed no reversal of strand asymmetry. Gene rearrangements have been found in
the lower taxonomic levels of thrips. Three tRNA genes were translocated in the
genus Frankliniella and eight tRNA genes in the family Thripidae. Although the
gene arrangements of mt genomes of all three thrips species differ massively from
the ancestral insect, they are all very similar to each other, indicating that
there was a large rearrangement somewhere before the most recent common ancestor
of these three species and very little genomic evolution or rearrangements after
then. The extremely similar sequences among the CRs suggest that they are ongoing
concerted evolution. Analyses of the up and downstream sequence of CRs reveal
that the CR2 is actually the ancestral CR. The three CRs are in the same spot in
each of the three thrips mt genomes which have the identical inverted genes.
These characteristics might be obtained from the most recent common ancestor of
this three thrips. Above observations suggest that the mt genomes of the three
thrips keep a single massive rearrangement from the common ancestor and have low
evolutionary rates among them.
PMID- 25128724
TI - Automated detection of 50-kHz ultrasonic vocalizations using template matching in
XBAT.
AB - BACKGROUND: Ultrasonic vocalizations (USVs) have been utilized to infer animals'
affective states in multiple research paradigms including animal models of drug
abuse, depression, fear or anxiety disorders, Parkinson's disease, and in
studying neural substrates of reward processing. Currently, the analysis of USV
data is performed manually, and thus is time consuming. NEW METHOD: The goal of
the present study was to develop a method for automated USV recognition using a
'template detection' procedure for vocalizations in the 50-kHz range (35-80kHz).
The detector is designed to run within XBAT, a MATLAB graphical user interface
and extensible bioacoustics tool developed at Cornell University. RESULTS:
Results show that this method is capable of detecting >90% of emitted USVs and
that time spent analyzing data by experimenters is greatly reduced. COMPARISON
WITH EXISTING METHODS: Currently, no viable and publicly available methods exist
for the automated detection of USVs. The present method, in combination with the
XBAT environment is ideal for the USV community as it allows others to (1) detect
USVs within a user-friendly environment, (2) make improvements to the detector
and disseminate and (3) develop new tools for analysis within the MATLAB
environment. CONCLUSIONS: The present detector provides an open-source, accurate
method for the detection of 50-kHz USVs. Ongoing research will extend the current
method for use in the 22-kHz frequency range of ultrasonic vocalizations.
Moreover, collaborative efforts among USV researchers may enhance the
capabilities of the current detector via changes to the templates and the
development of new programs for analysis.
PMID- 25128726
TI - Analysis of the transcriptome of Marsdenia tenacissima discovers putative
polyoxypregnane glycoside biosynthetic genes and genetic markers.
AB - Marsdenia tenacissima is a well-known anti-cancer medicinal plant used in
traditional Chinese medicine due to bioactive constituents of polyoxypregnane
glycosides, such as tenacissosides, marsdenosides and tenacigenosides. Genomic
information regarding this plant is very limited, and rare information is
available about the biosynthesis of polyoxypregnane glycosides. To facilitate the
basic understanding about the polyoxypregnane glycoside biosynthetic pathways, de
novo assembling was performed to generate a total of 73,336 contigs and 65,796
unigenes, which represent the first transcriptome of this species. These included
27 unigenes that were involved in steroid biosynthesis and could be related to
pregnane backbone biosynthesis. The expression patterns of six unigenes involved
in polyoxypregnane biosynthesis were analyzed in leaf and stem tissues by
quantitative real time PCR (qRT-PCR) to explore their putative function.
Furthermore, a total of 15,295 simple sequence repeats (SSRs) were identified
from 11,911 unigenes, of which di-nucleotide motifs were the most abundant.
PMID- 25128727
TI - External air compression: A rare cause of blunt esophageal injury, managed by a
stent.
AB - INTRODUCTION: Blunt esophageal injuries secondary to external air compression of
anterior chest and abdomen complicated with esophageal perforation are uncommon
events associated with worse outcomes. PRESENTATION OF CASE: We reported a rare
case of esophageal perforation following an external air-compression injury along
with the relevant review of literatures. The patient presented with chest pain
and shortness of breath and was managed with tube thoracostomy, followed by
thoracotomy and eventually with temporary endoscopic stenting. DISCUSSION: In
such trauma case, the external pressurized air forms a shock wave which usually
directed to the hollow viscus. Patients with external air-compression injury
presented with chest pain and pneumothorax should be suspected for esophageal
perforation. CONCLUSION: High index of suspicion is needed for early diagnosis of
esophageal perforation after blunt trauma. Appropriate drainage, antibiotic and
temporary endoscopic esophageal stenting may be an optimal approach in selected
patients, especially with delayed diagnosis.
PMID- 25128728
TI - Idiopathic bilateral antral exostoses: A rare case in maxillary sinus.
AB - INTRODUCTION: Exostoses in paranasal sinuses have been reported in the
otolaryngology literature, but they have not been described in the dental
literature to our knowledge. The aim of this article is to describe an idiopathic
and rare case of bilateral exostosis obtained by cone-beam computed tomography.
PRESENTATION OF CASE: The case shows a healthy and asymptomatic patient with a
different size and form of exostoses in both maxillary sinuses. DISCUSSION: It is
difficult to clinically diagnose the antral exostosis due the asymptomatic nature
of this condition, unless the approach would be through endoscope. Sometimes this
condition is related with nasal irrigants, however in this case the patient
asserted not having used nasal irrigation ever; thus, it is impossible to relate
this kind of treatment as a principal cause. CONCLUSION: The published data of
exostoses in maxillary sinus seem to be limited in the dental literature, and
this condition is important to consider in an implant treatment planning. Also,
it is important to perform a follow-up of the cases in trying to find the
possible causes of exostosis.
PMID- 25128729
TI - Recurrent respiratory distress and cardiopulmonary arrest caused by
megaoesophagus secondary to achalasia.
AB - INTRODUCTION: Respiratory distress and arrest from tracheal compression secondary
to megaoesophagus are rare complications of achalasia. We present the case of a
man with end-stage achalasia who required oesophagectomy to prevent recurrent
life-threatening tracheal compression and respiratory arrest. A literature review
is also presented. PRESENTATION OF CASE: A 40-year old man presented with post
prandial stridor which resolved spontaneously, later being diagnosed with
achalasia. He underwent pneumatic dilatation year later, intended as definitive
treatment. Despite intervention, the patient had developed megaoesophagus. One
month later he presented with tracheal compression and cardiorespiratory arrest
but was successfully resuscitated. He subsequently underwent elective
oesophagectomy. DISCUSSION: Over 40 case reports of achalasia presenting with
stridor have been published. However, only three cases (all female, age range, 35
79 years old) of cardiac, respiratory or cardiorespiratory arrest have been
published. The definitive treatments received by these patients were botulinum
toxin injections, open Heller cardiomyotomy with Dor fundoplication and pneumatic
dilatation. None of these patients suffered recurrent respiratory distress
following definitive treatment. The patient currently reported was unique as he
suffered cardiorespiratory arrest following an intended definitive treatment,
pneumatic dilatation. As such oesophagectomy was considered the greatest risk
reduction intervention. CONCLUSION: Oesophagectomy should be considered for
patients with end-stage achalasia and mega-oesophagus causing respiratory
compromise to avoid potential fatal complications such as tracheal compression
and subsequent respiratory arrest.
PMID- 25128730
TI - Can pelvic tilting be ignored in total hip arthroplasty?
AB - INTRODUCTION: The orientation of acetabular component is influenced by pelvic
tilt, body position and individual variation in pelvic parameters. Most post
operative adverse events may be attributed to malposition of the component in the
functional position. There is evidence that orientation of the pelvis changes
from the supine to standing position. Authors report a case of recurrent
dislocation after total hip arthroplasty due to excessive pelvic tilting.
PRESENTATION OF CASE A 69-year old female with coxarthrosis had undergone total
hip replacement with recurrent dislocation of the hip on bearing weight in spite
of using constrained acetabular component. DISCUSSION: Our case report
substantiates the influence of pelvic tilt, incurred by a sagittal deformity of
spine, on dynamic orientation of the acetabular cup which was positioned in
accordance with the anatomic landmarks alone. If the reference is only bony
architecture and dynamic positions of the pelvis are not taken into account,
improper functional orientation of the acetabular cup can result in sitting and
standing positions. These can induce instability even in anatomically
appropriately oriented acetabular component. CONCLUSION: The sagittal position of
pelvis is a key factor in impingement and dislocation after total hip
arthroplasty. Pelvic tilting affects the position of acetabular component in the
sagittal plane of the body as compared with its anatomic position in the pelvis.
We suggest a preoperative lateral view of spine-pelvis, in upright and supine
position for evaluation of a corrective adaptation of the acetabular cup
accordingly with pelvic balance.
PMID- 25128731
TI - Kidney stem cells in development, regeneration and cancer.
AB - The generation of nephrons during development depends on differentiation via a
mesenchymal to epithelial transition (MET) of self-renewing, tissue-specific stem
cells confined to a specific anatomic niche of the nephrogenic cortex. These
cells may transform to generate oncogenic stem cells and drive pediatric renal
cancer. Once nephron epithelia are formed the view of post-MET tissue renal
growth and maintenance by adult tissue-specific epithelial stem cells becomes
controversial. Recently, genetic lineage tracing that followed clonal evolution
of single kidney cells showed that the need for new cells is constantly driven by
fate-restricted unipotent clonal expansions in varying kidney segments arguing
against a multipotent adult stem cell model. Lineage-restriction was similarly
maintained in kidney organoids grown in culture. Importantly, kidney cells in
which Wnt was activated were traced to give significant clonal progeny indicating
a clonogenic hierarchy. In vivo nephron epithelia may be endowed with the
capacity akin to that of unipotent epithelial stem/progenitor such that under
specific stimuli can clonally expand/self renew by local proliferation of mature
differentiated cells. Finding ways to ex vivo preserve and expand the observed in
vivo kidney-forming capacity inherent to both the fetal and adult kidneys is
crucial for taking renal regenerative medicine forward. Some of the strategies
used to achieve this are sorting human fetal nephron stem/progenitor cells,
growing adult nephrospheres or reprogramming differentiated kidney cells toward
expandable renal progenitors.
PMID- 25128732
TI - Patterning the renal vascular bed.
AB - The renal vascular bed has a stereotypic architecture that is essential for the
kidney's role in excreting metabolic waste and regulating the volume and
composition of body fluids. The kidney's excretory functions are dependent on the
delivery of the majority of renal blood flow to the glomerular capillaries, which
filter plasma removing from it metabolic waste, as well as vast quantities of
solutes and fluids. The renal tubules reabsorb from the glomerular filtrate
solutes and fluids required for homeostasis, while the post-glomerular capillary
beds return these essential substances back into the systemic circulation. Thus,
the kidney's regulatory functions are dependent on the close proximity or
alignment of the post-glomerular capillary beds with the renal tubules. This
review will focus on our current knowledge of the mechanisms controlling the
embryonic development of the renal vasculature. An understanding of this process
is critical for developing novel therapies to prevent vessel rarefaction and will
be essential for engineering renal tissues suitable for restoring kidney function
to the ever-increasing population of patients with end stage renal disease.
PMID- 25128734
TI - Use of maternal flecainide concentration in management of fetal supraventricular
tachycardia: a step in the right direction.
PMID- 25128733
TI - Left atrial appendage morphology and thromboembolic risk after catheter ablation
for atrial fibrillation.
AB - BACKGROUND: In patients with atrial fibrillation (AF), left atrial appendage
(LAA) morphology has been suggested to modify risk of thromboembolic events
(TEs). OBJECTIVE: In this study, we tested the hypothesis that a TE after AF
catheter ablation is associated with LAA characteristics. METHODS: Of 2069
patients included in the Leipzig Heart Center AF Ablation Registry, 15 (0.7%)
suffered a TE (excluding events within 30 days) during follow-up (ie, 3.078
patient-years). Those patients were matched for CHA2DS2-VASc criteria with 115
patients without TE, and computed tomography (n = 120) or magnetic resonance
imaging (n = 10) data were also compared. LAA volume, morphology (cactus, chicken
wing, windsock, and cauliflower), and takeoff (higher/lower) in relation to the
adjacent pulmonary vein were determined. RESULTS: After patients were followed
for a median period of 24 months, 67% of the patients remained in sinus rhythm.
Patients with TE had a higher AF recurrence rate (73% vs 28%; P = .001) and a
higher incidence of superior LAA takeoff (ie, higher than that of the left
superior pulmonary vein; 80% vs 37%; P = .002), while LAA morphologies and other
LAA characteristics were similar between groups. Multivariate Cox regression
analysis revealed AF recurrence (hazard ratio 6.2; 95% confidence interval 2.0
19.6; P = .002) and superior LAA takeoff (hazard ratio 4.9; 95% confidence
interval 1.4-17.4; P = .014) as TE predictors. There was a negative correlation
between heart rate and LAA flow (r = -.22 cm/s per beat/min; P = .016), which was
even more pronounced for the superior LAA takeoff (r = -.28 cm/s; P = .045).
CONCLUSION: AF recurrence and higher LAA takeoff are associated with
thromboembolism after AF ablation, while LAA morphology is not. These results may
have an implication for improved postablation management.
PMID- 25128735
TI - Generation of physiological and pathological high frequency oscillations: the
role of perisomatic inhibition in sharp-wave ripple and interictal spike
generation.
AB - Sharp-wave-ripple complexes (SWRs) and interictal-spikes are physiological and
pathological forms of irregularly occurring transient high activity events in the
hippocampal EEG. They share similar features and carry high-frequency
oscillations with different spectral features. Recent results reveal similarities
and differences in the generation of the two types of transients, and argue that
parvalbumin containing basket cells (PVBCs) are crucial in synchronizing neuronal
activity in both cases. SWRs are generated in the reciprocally connected network
of inhibitory PVBCs, while in the pathological case, synchronous failure of
perisomatic inhibition triggers massive pyramidal cell burst firing. While
physiological ripple oscillation is primarily the result of phasic perisomatic
inhibitory currents, pathological high-frequency ripples are population spikes of
partially synchronous, massively bursting, uninhibited pyramidal cells.
PMID- 25128736
TI - Knowledge base and neural network approach for protein secondary structure
prediction.
AB - Protein structure prediction is of great relevance given the abundant genomic and
proteomic data generated by the genome sequencing projects. Protein secondary
structure prediction is addressed as a sub task in determining the protein
tertiary structure and function. In this paper, a novel algorithm, KB-PROSSP-NN,
which is a combination of knowledge base and modeling of the exceptions in the
knowledge base using neural networks for protein secondary structure prediction
(PSSP), is proposed. The knowledge base is derived from a proteomic sequence
structure database and consists of the statistics of association between the 5
residue words and corresponding secondary structure. The predicted results
obtained using knowledge base are refined with a Backpropogation neural network
algorithm. Neural net models the exceptions of the knowledge base. The Q3
accuracy of 90% and 82% is achieved on the RS126 and CB396 test sets respectively
which suggest improvement over existing state of art methods.
PMID- 25128737
TI - Interactome analyses of Salmonella pathogenicity islands reveal SicA
indispensable for virulence.
AB - BACKGROUND: Serovars of Salmonella enterica, namely Typhi and Typhimurium,
reportedly, are the bacterial pathogens causing systemic infections like
gastroenteritis and typhoid fever. To elucidate the role and importance in such
infection, the proteins of the Type III secretion system of Salmonella
pathogenicity islands and two component signal transduction systems, have been
mainly focused. However, the most indispensable of these virulent ones and their
hierarchical role has not yet been studied extensively. RESULTS: We have adopted
a theoretical approach to build an interactome comprising the proteins from the
Salmonella pathogeneicity islands (SPI) and two component signal transduction
systems. This interactome was then analyzed by using network parameters like
centrality and k-core measures. An initial step to capture the fingerprint of the
core network resulted in a set of proteins which are involved in the process of
invasion and colonization, thereby becoming more important in the process of
infection. These proteins pertained to the Inv, Org, Prg, Sip, Spa, Ssa and Sse
operons along with chaperone protein SicA. Amongst them, SicA was figured out to
be the most indispensable protein from different network parametric analyses.
Subsequently, the gene expression levels of all these theoretically identified
important proteins were confirmed by microarray data analysis. Finally, we have
proposed a hierarchy of the proteins involved in the total infection process.
This theoretical approach is the first of its kind to figure out potential
virulence determinants encoded by SPI for therapeutic targets for enteric
infection. CONCLUSIONS: A set of responsible virulent proteins was identified and
the expression level of their genes was validated by using independent, published
microarray data. The result was a targeted set of proteins that could serve as
sensitive predictors and form the foundation for a series of trials in the wet
lab setting. Understanding these regulatory and virulent proteins would provide
insight into conditions which are encountered by this intracellular enteric
pathogen during the course of infection. This would further contribute in
identifying novel targets for antimicrobial agents.
PMID- 25128738
TI - Quantification and geometric analysis of coiling patterns in gastropod shells
based on 3D and 2D image data.
AB - The morphology of gastropod shells has been a focus of analyses in ecology and
evolution. It has recently emerged as an important issue in developmental
biology, thanks to recent advancements in molecular biological techniques. The
growing tube model is a theoretical morphological model for describing various
coiling patterns of molluscan shells, and it is a useful theoretical tool to
relate local tissue growth with global shell morphology. However, the growing
tube model has rarely been adopted in empirical research owing to the difficulty
in estimating the parameters of the model from morphological data. In this
article, I solve this problem by developing methods of parameter estimation when
(1) 3D Computed Tomography (CT) data are available and (2) only 2D image data
(such as photographs) are available. When 3D CT data are available, the
parameters can be estimated by fitting an analytical solution of the growing tube
model to the data. When only 2D image data are available, we first fit Raup's
model to the 2D image data and then convert the parameters of Raup's model to
those of the growing tube model. To illustrate the use of these methods, I apply
them to data generated by a computer simulation of the model. Both methods work
well, except when shells grow without coiling. I also demonstrate the
effectiveness of the methods by applying the model to actual 3D CT data and 2D
image data of land snails. I conclude that the method proposed in this article
can reconstruct the coiling pattern from observed data.
PMID- 25128739
TI - Hispolon inhibition of inflammatory apoptosis through reduction of iNOS/NO
production via HO-1 induction in macrophages.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Phellinus linteus (Berkeley & Curtis), a well
known medical fungus, has long been used as a traditional medicine in Oriental
countries to treat various diseases, and hispolon (HIS) is one of its bioactive
components. HIS is known to possess potent antineoplastic and antiviral
properties; however, its effect on inflammatory apoptosis is still undefined.
MATERIALS AND METHODS: RAW264.7 macrophages were incubated with HIS for 30 min
followed by LPS, LTA, or PGN stimulation for 12h. The expression of indicated
proteins AP-1 and NF-kappaB transcriptional activities was examined by Western
blotting using specific antibodies. Levels of NO and ROS were examined by Griess
reaction, and DCHF-DA staining via flow cytometric analysis, respectively. AP-1
and NF-kappaB transcriptional activities were detected by luciferase reporter
assay. Knockdown of HO-1 protein expression was performed by transfection of
macrophages with HO-1 siRNA. Pharmacological inhibitors including ROS scavenger
NAC, JNK inhibitor SP600125, NF-kappaB inhibitor BAY117082 were applied for
mechanism study. RESULTS: HIS showed concentration-dependent inhibition of LPS,
LTA, and PGN-induced iNOS protein expressions and NO production by RAW264.7
macrophages. Accordingly, HIS protected RAW264.7 cells from LPS-, LTA-, and PGN
induced apoptosis. Increased HO-1 by HIS was detected at both protein and mRNA
levels along with an increase in intracellular peroxide, and this was inhibited
by the translational inhibitor, cycloheximide (CHX), the transcriptional
inhibitor, actinomycin D (Act D), and the reactive oxygen species scavenger, N
acetylcysteine (NAC). A mechanistic study indicated that inhibition of c-Jun N
terminal kinase (JNK) protein phosphorylation, and activator protein (AP)-1 and
nuclear factor (NF)-kappaB activation were involved in the anti-inflammatory
actions of HIS in macrophages. A structure-activity relationship analysis showed
that HIS expressed the most potent effect of inhibiting iNOS and apoptosis
elicited by LPS, LTA, and PGN with a significant increase in HO-1 protein in
macrophages. CONCLUSIONS: Evidence supporting HIS prevention of inflammatory
apoptosis via blocking NO production and inducing HO-1 protein expression in
macrophages is provided, and the hydroxyl at position C3 is a critical
substitution for the anti-inflammatory actions of HIS.
PMID- 25128740
TI - Unraveling novel broad-spectrum antibacterial targets in food and waterborne
pathogens using comparative genomics and protein interaction network analysis.
AB - Food and waterborne diseases are a growing concern in terms of human morbidity
and mortality worldwide, even in the 21st century, emphasizing the need for new
therapeutic interventions for these diseases. The current study aims at
prioritizing broad-spectrum antibacterial targets, present in multiple food and
waterborne bacterial pathogens, through a comparative genomics strategy coupled
with a protein interaction network analysis. The pathways unique and common to
all the pathogens under study (viz., methane metabolism, d-alanine metabolism,
peptidoglycan biosynthesis, bacterial secretion system, two-component system, C5
branched dibasic acid metabolism), identified by comparative metabolic pathway
analysis, were considered for the analysis. The proteins/enzymes involved in
these pathways were prioritized following host non-homology analysis,
essentiality analysis, gut flora non-homology analysis and protein interaction
network analysis. The analyses revealed a set of promising broad-spectrum
antibacterial targets, present in multiple food and waterborne pathogens, which
are essential for bacterial survival, non-homologous to host and gut flora, and
functionally important in the metabolic network. The identified broad-spectrum
candidates, namely, integral membrane protein/virulence factor (MviN), preprotein
translocase subunits SecB and SecG, carbon storage regulator (CsrA), and nitrogen
regulatory protein P-II 1 (GlnB), contributed by the peptidoglycan pathway,
bacterial secretion systems and two-component systems, were also found to be
present in a wide range of other disease-causing bacteria. Cytoplasmic proteins
SecG, CsrA and GlnB were considered as drug targets, while membrane proteins MviN
and SecB were classified as vaccine targets. The identified broad-spectrum
targets can aid in the design and development of antibacterial agents not only
against food and waterborne pathogens but also against other pathogens.
PMID- 25128741
TI - Role of microRNAs in the modulation of diabetic retinopathy.
AB - Diabetic retinopathy (DR) is the leading cause of vision loss in the working-age
adults. It affects a third of diabetics. Diabetic macular edema, an advanced
complication of DR, develops in nearly 7% of diabetic patients. MicroRNAs
(miRNAs) are a novel group of non-coding small RNAs that post-transcriptionally
control gene expression by promoting either degradation or translational
repression of target messenger RNA. They are implicated in a large variety of
physiological and pathophysiological processes, including glucose homeostasis,
angiogenesis and modulation of inflammatory response. MiRNAs also play a critical
role in the pathogenesis of diabetes and the related micro- and macrovascular
complications. The purpose of this review is to describe the potential role of
miRNAs in diabetes and evaluate their implication in DR. MiRNAs involved in the
modulation of glucose metabolism (insulin secretion and sensitivity) and MiRNAs
playing a role in the pathogenesis of DR with their potential target genes are
reviewed. Understanding MiRNAs implication in DR could be helpful for developing
new gain- or loss- of -function strategies in order to establish effective
treatments and reduce the rate of visual disability due to progression of
retinopathy.
PMID- 25128743
TI - Nonalcoholic fatty liver disease: A main driver of insulin resistance or a
dangerous liaison?
AB - Insulin resistance is one of the key components of the metabolic syndrome and it
eventually leads to the development of type 2 diabetes, making it one of the
biggest medical problems of modern society. Nonalcoholic fatty liver disease
(NAFLD) and nonalcoholic steatohepatitis (NASH) are tightly associated with
insulin resistance. While it is fairly clear that insulin resistance causes
hepatic steatosis, it is not known if NAFLD causes insulin resistance. Hepatic
inflammation and lipid accumulation are believed to be the main drivers of
hepatic insulin resistance in NAFLD. Here we give an overview of the evidence
linking hepatic lipid accumulation to the development of insulin resistance,
including the accumulation of triacylglycerol and lipid metabolites, such as
diacylglycerol and ceramides. In particular, we discuss the role of obesity in
this relation by reviewing the current evidence in terms of the reported changes
in body weight and/or adipose tissue mass. We further discuss whether the
activation or inhibition of inflammatory pathways, Kupffer cells and other immune
cells influences the development of insulin resistance. We show that, in contrast
to what is commonly believed, neither hepatic steatosis nor hepatic inflammation
is sufficient to cause insulin resistance. Many studies show that obesity cannot
be ignored as an underlying factor in this relationship and NAFLD is therefore
less likely to be one of the main drivers of insulin resistance.
PMID- 25128742
TI - Novel role of silent information regulator 1 in acute endothelial cell oxidative
stress injury.
AB - Silent information regulator 1 (SIRT1), a class III histone deacetylase, retards
aging and plays roles in cellular oxidative stress injury (OSI). However, the
biological context in which SIRT1 promotes oxidative injury is not fully
understood. Here, we show that SIRT1 essentially mediates hydrogen peroxide
(H2O2)-induced cytotoxicity in human umbilical vein endothelial cell (HUVEC). In
HUVECs, SIRT1 protein expression was significantly increased in a dose-dependent
manner after H2O2 treatment, whereas the acetylation levels of the NF-kappaB p65
subunit and p53 were decreased. EX527 (a specific SIRT1 inhibitor) conferred
protection to the HUVECs against H2O2, as indicated by an improved cell
viability, adhesion, an enhanced migratory ability, a decreased apoptotic index,
decreased reactive oxygen species (ROS) production and reductions in several
biochemical parameters. Immunofluorescence and Western blot analyses demonstrated
that H2O2 treatment up-regulated SIRT1, phosphorylated-JNK (p-JNK), p-p38MAPK,
and p-ERK expression. EX527 pretreatment reversed these effects on SIRT1, p-JNK,
and p-p38MAPK but further increased the p-ERK levels. Similar results were
confirmed in SIRT1 siRNA experiments. In summary, SIRT1 signaling pathway
inhibition imparts protection against acute endothelial OSI, and modulation of
MAPKs (JNK, p38MAPK, and ERK) may be involved in the protective effect of SIRT1
inhibition.
PMID- 25128744
TI - Prognostic value of glomerular filtration changes versus natriuretic response in
decompensated heart failure with reduced ejection.
AB - BACKGROUND: Glomerular filtration rate (GFR) and natriuretic response to
diuretics represent important treatment targets in acute decompensated heart
failure (ADHF). METHODS AND RESULTS: Consecutive ADHF patients (n = 50) with
ejection fraction <= 45% and clinical signs of volume overload received protocol
driven decongestive therapy. Serum creatinine (Cr), cystatin C (CysC), and beta
trace protein (betaTP) were measured on admission and three subsequent days of
treatment. Worsening renal function (WRF) was defined as a >= 0.3 increase in
absolute biomarker levels or >= 20% decrease in estimated GFR. Consecutive 24
hour urinary collections were simultaneously performed to measure Cr clearance
and natriuresis. Serum Cr, CysC, and betaTP were strongly correlated at admission
(rho = 0.788-0.909) and during decongestive treatment (rho = 0.884-888).
Moreover, derived GFR estimates correlated well with Cr clearance (rho = 0.820
0.908). Nevertheless, WRF incidence differed markedly according to Cr- (26%-30%),
CysC- (46%-54%), or betaTP-based definitions (31%-48%). WRF by any definition was
not associated with all-cause mortality or ADHF readmission, in contrast to
stronger natriuresis per loop diuretic dose [hazard ratio 0.20 (95% confidence
interval 0.06-0.64); P = .007]. CONCLUSIONS: Serial measurements of CysC/betaTP,
compared with serum Cr, more frequently indicate WRF during decongestive
treatment in ADHF. However, adverse clinical outcome in such patients might be
better predicted by the natriuretic response to diuretic therapy.
PMID- 25128746
TI - Survival rates in out-of-hospital cardiac arrest patients transported without
prehospital return of spontaneous circulation: an observational cohort study.
AB - BACKGROUND: Some Emergency Medical Services currently use just one component of
the Universal Termination of Resuscitation (TOR) Guideline, the absence of
prehospital return of spontaneous circulation (ROSC), as the single criteria to
terminate resuscitation, which may deny transport to potential survivors.
OBJECTIVE: This study aimed to report the survival to hospital discharge rate in
non-traumatic, adult out-of-hospital cardiac arrest (OHCA) patients transported
to hospital without a prehospital ROSC. METHODS: An observational study of OHCA
patients without a prehospital ROSC who met the Universal TOR Guideline for
transport to hospital with ongoing resuscitation. Multivariable logistic
regression was used to determine the association of each variable with survival
to hospital discharge. RESULTS: Of 20,207 OHCA treated by EMS, 3374 (16.4%) did
not have a prehospital ROSC but met the Universal TOR guideline for transport to
hospital with ongoing resuscitation. Of these patients, 122 (3.6%) survived to
hospital discharge. Survival to discharge was associated with initial shockable
VF/VT rhythms (OR 5.07; 95% CI 2.77-9.30), EMS-witnessed arrests (OR 3.51; 95% CI
1.73-7.15), bystander-witnessed arrests (OR 2.11; 95% CI 1.18-3.77), and public
locations (OR 1.57; 95% CI 1.02-2.40). CONCLUSION: In OHCA patients without a
prehospital ROSC who met the Universal TOR Guideline for transport with ongoing
resuscitation survival rates were above the 1% futility rate. Employing only the
lack of ROSC as criteria for termination of resuscitation may miss survivors
after OHCA.
PMID- 25128745
TI - Prognostic value of elevated serum ceruloplasmin levels in patients with heart
failure.
AB - BACKGROUND: Ceruloplasmin (Cp) is a copper-binding acute-phase protein that is
increased in inflammatory states and deficient in Wilson's disease. Recent
studies demonstrate that increased levels of Cp are associated with increased
risk of developing heart failure. Our objective was to test the hypothesis that
serum Cp provides incremental and independent prediction of survival in stable
patients with heart failure. METHODS AND RESULTS: We measured serum Cp levels in
890 patients with stable heart failure undergoing elective cardiac evaluation
that included coronary angiography. We examined the role of Cp levels in
predicting survival over 5 years of follow-up. Mean Cp level was 26.6 +/- 6.9
mg/dL and demonstrated relatively weak correlation with B-type natriuretic
peptide (BNP; r = 0.187; P < .001). Increased Cp levels were associated with
increased 5-year all-cause mortality (quartile [Q] 4 vs Q1 hazard ratio [HR] 1.9,
95% confidence interval [CI] 1.4-2.8; P < .001). When controlled for coronary
disease traditional risk factors, creatinine clearance, dialysis, body mass
index, medications, history of myocardial infarction, BNP, left ventricular
ejection fraction (LVEF), heart rate, QRS duration, left bundle branch blockage,
and implantable cardioverter-defibrillator placement, higher Cp remained an
independent predictor of increased mortality (Q4 vs Q1 HR 1.7, 95% CI 1.1-2.6; P
< .05). Model quality was improved with addition of Cp to the aforementioned
covariables (net reclassification improvement of 9.3%; P < .001). CONCLUSIONS:
Ceruloplasmin is an independent predictor of all-cause mortality in patients with
heart failure. Measurement of Cp may help to identify patients at heightened
mortality risk.
PMID- 25128747
TI - Occurrence of the three major Vibrio species pathogenic for human in seafood
products consumed in France using real-time PCR.
AB - Vibrio spp. have emerged as a serious threat to human health worldwide. Vibrio
parahaemolyticus, Vibrio cholerae and Vibrio vulnificus are of particular concern
as they have been linked to gastrointestinal infections and septicemia associated
with the consumption of raw or undercooked seafood. We developed hydrolysis probe
based real-time PCR systems with an internal amplification control for the
detection of these species. We applied these systems to a total of 167 fresh or
frozen crustacean, fish and shellfish samples consumed in France. Of them, 34.7%
(n=58) were positive for Vibrio. V. parahaemolyticus was the most common, in
31.1% of samples, followed by V. vulnificus in 12.6% and V. cholerae in 0.6%.
Furthermore, V. parahaemolyticus and V. vulnificus were present simultaneously in
9.6% of samples. Virulence genes (tdh and trh sequences) were present in 25% of
the V. parahaemolyticus-positive samples. The V. cholerae strain detected was non
toxigenic. The densities of V. parahaemolyticus and V. cholerae ranged from
<10(2) to 10(4)bacteria/g of seafood. All samples positive for V. vulnificus
displayed low-level contamination with fewer than 10(2)bacteria/g. Our findings
indicate that seafood consumption presents a potential risk to human health in
France and highlight the importance of tools for a preventive consumer protection
policy.
PMID- 25128749
TI - Impaired coronary microvascular and left ventricular diastolic function in
patients with inflammatory bowel disease.
AB - BACKGROUND AND AIM: Increased incidence of coronary vascular events in patients
with inflammatory bowel disease (IBD) is known. However, the association between
coronary microvascular function and IBD has not been fully defined. We aimed to
investigate whether coronary flow reserve (CFR) and left ventricular diastolic
function were impaired in IBD patients. METHODS: Seventy-two patients with IBD
(36 patients with ulcerative colitis [UC] and 36 Crohn's disease [CD]) were
registered. Each subject was evaluated after a minimum 15-day attack-free period.
For the control group, 36 age- and sex-matched healthy volunteers were included
into the study. IBD clinical disease activity in UC was assessed by the Truelove
Witts Index (TWAS) and in CD by the Crohn's Disease Activity Index (CDAI). In
each subject, CFR was measured through transthoracic Doppler echocardiography.
RESULTS: Compared to the controls, the CD group and UC group had significantly
higher high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation
rate. Baseline diastolic peak flow velocity (DPFV) of the left anterior
descending artery (LAD) was significantly higher in the IBD group (24.1+/-3.9 vs.
22. 4+/-2.9, p<0.05), and hyperemic DPFV (56.1+/-12.5 vs. 70.6+/-15.3, p<0.05)
and CFR (2.34+/-0.44 vs. 3.14+/-0.54, p<0.05) were significantly lower in the IBD
group than in the control group. In stepwise linear regression analysis, hs-CRP
and lateral Em/Am ratio were independently correlated with CFR. CONCLUSION: CFR,
reflecting coronary microvascular function, is impaired in patients with IBD. CFR
and left ventricular diastolic function parameters are well correlated with hs
CRP.
PMID- 25128748
TI - Effects of intracerebroventricular injections of 5-HT on systemic vascular
resistances of conscious rats.
AB - The aims of this study were to determine (i) the effects of
intracerebroventricular (i.c.v.) injections of 5-hydroxytryptamine (5-HT, 10MUg)
on mean arterial blood pressure (MAP), heart rate (HR) and mesenteric (MR), renal
(RR) and hindquarter (HQR) vascular resistances of conscious rats, (ii) the
central 5-HT receptor subtype which mediates these effects, and (iii) the role of
nitric oxide (NO) in the expression of these responses. The i.c.v. injection of 5
HT had minor effects on MAP but produced a decrease in HR (-18+/-4%), which
lasted for 20min. The i.c.v. injection of 5-HT elicited marked increases in MR
(+50+/-7%) and reductions in HQR (-31+/-3%). These responses occurred promptly
and lasted for 25-35min. 5-HT also produced a transient decrease in RR (-26+/-8%
at 10min). All of these responses were prevented by the prior i.c.v. injection of
the 5-HT1/5-HT2-receptor antagonist, methysergide (10MUg). The intravenous
injection of the NO synthesis inhibitor, L-NAME (25MUmol/kg), produced a
sustained pressor response, bradycardia and increases in MR, RR and HQR.
Subsequent i.c.v. injection of 5-HT produced a minor pressor response (+7+/-2%),
bradycardia (-18+/-3%), an increase in MR (+52+/-8%) but no decreases in RR or
HQR. This study demonstrates that i.c.v. 5-HT differentially affects peripheral
vascular resistances by activation of central 5-HT1/5-HT2-receptors. It appears
that L-NAME did not interfere with the central actions of 5-HT as it did not
prevent the 5-HT-induced bradycardia or mesenteric vasoconstriction. Since the 5
HT-induced falls in RR and HQR were abolished by L-NAME, it is possible that
these responses are mediated by an active neurogenic process involving the
release of NO within the vasculature.
PMID- 25128751
TI - Assessment of presentation methods for ReFace computerized facial approximations.
AB - Facial approximations (whether clay sculptures, sketches, or computer-generated)
can be presented to the public in a variety of layouts, but there are currently
no clear indicators as to what style of presentation is most effective at
eliciting recognition. The primary purpose of this study is to determine which of
five presentation methods produces the most favorable recognition results. A
secondary goal of the research is to evaluate a new method for assessing the
accuracy of facial approximations. Previous studies have evaluated facial
approximation effectiveness using standards similar to studies of eyewitness
identification in which a single, definitive choice must be made by the research
participant. These criteria seem inappropriate given that facial approximation is
strictly an investigative tool to help narrow the search for potential matching
candidates in the process of identification. Results from the study showed a
higher performance for methods utilizing more than one image of the
approximation, but which specific method performed best varied among
approximation subjects. Also, results for all five presentation methods showed
that, when given the opportunity to select more than one approximation,
participants were consistently better at identifying the correct approximation as
one of a few possible matches to the missing person than they were at singling
out the correct approximation. This suggests that facial approximations have
perhaps been undervalued as investigative tools in previous research.
PMID- 25128752
TI - Cortical modulation of pain: comments on "exacerbation of tonic but not phasic
pain by entorhinal cortex lesions".
PMID- 25128750
TI - Engineering in vivo gradients of sphingosine-1-phosphate receptor ligands for
localized microvascular remodeling and inflammatory cell positioning.
AB - Biomaterial-mediated controlled release of soluble signaling molecules is a
tissue engineering approach to spatially control processes of inflammation,
microvascular remodeling and host cell recruitment, and to generate biochemical
gradients in vivo. Lipid mediators, such as sphingosine 1-phosphate (S1P), are
recognized for their essential roles in spatial guidance, signaling and highly
regulated endogenous gradients. S1P and pharmacological analogs such as FTY720
are therapeutically attractive targets for their critical roles in the
trafficking of cells between blood and tissue spaces, both physiologically and
pathophysiologically. However, the interaction of locally delivered sphingolipids
with the complex metabolic networks controlling the flux of lipid species in
inflamed tissue has yet to be elucidated. In this study, complementary in vitro
and in vivo approaches are investigated to identify relationships between polymer
composition, drug release kinetics, S1P metabolic activity, signaling gradients
and spatial positioning of circulating cells around poly(lactic-co-glycolic acid)
biomaterials. Results demonstrate that biomaterial-based gradients of S1P are
short-lived in the tissue due to degradation by S1P lyase, an enzyme that
irreversibly degrades intracellular S1P. On the other hand, in vivo gradients of
the more stable compound, FTY720, enhance microvascular remodeling by selectively
recruiting an anti-inflammatory subset of monocytes (S1P3(high)) to the
biomaterial. Results highlight the need to better understand the endogenous
balance of lipid import/export machinery and lipid kinase/phosphatase activity in
order to design biomaterial products that spatially control the innate immune
environment to maximize regenerative potential.
PMID- 25128753
TI - Behavioral characteristics of subthreshold depression.
AB - BACKGROUND: This study examines differences in behavioral characteristics among
individuals who are not depressed and individuals with subthreshold depression,
and depression. METHODS: We conducted structured interviews with 111
undergraduate students, who also completed self-report scales. The participants
were divided into a non-depression group, a subthreshold depression group, and a
depression group based on results of the structured interview and the BDI-II.
RESULTS: There were significant differences in avoidance between depression group
and other two groups. Also, for the environmental rewards, there were significant
difference between the non-depressed group and the other two groups. LIMITATIONS:
The sample of depressed participants was small. The overall sample consisted only
undergraduate students. CONCLUSIONS: This study reported that there are different
behavioral characteristics among non-depression, subthreshold depression, and
depression groups. Whereas depression group is characterized by high frequency of
avoidance and low environmental rewards, subthreshold depression group is
characterized by only low environmental rewards.
PMID- 25128754
TI - Hospital management of self-harm patients and risk of repetition: systematic
review and meta-analysis.
AB - BACKGROUND: Self-harm is a common reason for hospital presentation; however,
evidence to guide clinical management of these patients to reduce their risk of
repeat self-harm and suicide is lacking. METHODS: We undertook a systematic
review to investigate whether between study differences in reported clinical
management of self-harm patients were associated with the risk of repeat self
harm and suicide. RESULTS: Altogether 64 prospective studies were identified that
described the clinical care of self-harm patients and the incidence of repeat
self-harm and suicide. The proportion of a cohort psychosocially assessed was not
associated with the recorded incidence of repeat self-harm or suicide; the
incidence of repeat self-harm was 16.7% (95% CI 13.8-20.1) in studies in the
lowest tertile of assessment levels and 19.0% (95% CI 15.7-23.0) in the highest
tertile. There was no association of repeat self-harm with differing levels of
hospital admission (n=47 studies) or receiving specialist follow-up (n=12
studies). In studies reporting on levels of hospital admission and suicide (n=5),
cohorts where a higher proportion of patients were admitted to a hospital bed
reported a lower incidence of subsequent suicide (0.6%, 95% CI 0.5-0.8) compared
to cohorts with lower levels of admission (1.9%, 95% CI 1.1-3.2). LIMITATIONS: In
some analyses power was limited due to the small number of studies reporting the
exposures of interest. Case mix and aspects of care are likely to vary between
studies. DISCUSSION: There is little clear evidence to suggest routine aspects of
self-harm patient care, including psychosocial assessment, reduce the risk of
subsequent suicide and repeat self-harm.
PMID- 25128755
TI - A framework for monitoring social process and outcomes in environmental programs.
AB - When environmental programs frame their activities as being in the service of
human wellbeing, social variables need to be integrated into monitoring and
evaluation (M&E) frameworks. This article draws upon ecosystem services theory to
develop a framework to guide the M&E of collaborative environmental programs with
anticipated social benefits. The framework has six components: program need,
program activities, pathway process variables, moderating process variables,
outcomes, and program value. Needs are defined in terms of ecosystem services, as
well as other human needs that must be addressed to achieve outcomes. The pathway
variable relates to the development of natural resource governance capacity in
the target community. Moderating processes can be externalities such as the
inherent capacity of the natural system to service ecosystem needs, local demand
for natural resources, policy or socio-economic drivers. Internal program
specific processes relate to program service delivery, targeting and participant
responsiveness. Ecological outcomes are expressed in terms of changes in
landscape structure and function, which in turn influence ecosystem service
provision. Social benefits derived from the program are expressed in terms of the
value of the eco-social service to user-specified goals. The article provides
suggestions from the literature for identifying indicators and measures for
components and component variables, and concludes with an example of how the
framework was used to inform the M&E of an adaptive co-management program in
western Kenya.
PMID- 25128756
TI - Enhanced contrast separation in scanning electron microscopes via a suspended
thin sample approach.
AB - A suspended-thin-sample (STS) approach for signal selection and contrast
separation is developed in scanning electron microscopes with commonly used
primary beam energies and traditional detectors. Topography contrast, electron
channeling contrast and composition contrast are separated and largely enhanced
from suspended thin samples of several hundred nanometers in thickness, which is
less than the escape depth of backscattered electrons. This imaging technique
enables to detect relatively pure secondary electron and elastic backscattered
electron singles, whereas suppress multiple inelastic scattering effects. The
provided contrast features are different from those of bulk samples, which are
largely mixed with inelastic scattering effects. The STS imaging concept and
method could be expected to have more applications in distinguishing materials of
nanostructures, multilayers, compounds and composites, as well as in SEM-based
electron backscatter diffraction, cathodoluminesence, and x-ray microanalysis.
PMID- 25128757
TI - PCSK9 levels in abdominally obese men: association with cardiometabolic risk
profile and effects of a one-year lifestyle modification program.
AB - OBJECTIVES: Studies performed in rodents have suggested a role for proprotein
convertase subtilisin/kexin type 9 (PCSK9) in insulin resistance and impaired
body fat distribution. Our objective was to examine the relationships between
markers of adiposity and insulin resistance and plasma PCSK9 levels in humans. In
addition, we explored the effect of a one-year lifestyle modification program on
plasma PCSK9 levels in abdominally obese, dyslipidemic men. METHODS: Plasma PCSK9
levels were measured by ELISA in 175 abdominally obese, dyslipidemic sedentary
men. Of these abdominally obese men, 117 non-diabetic individuals completed a one
year lifestyle modification program aiming at increasing cardiorespiratory
fitness levels and improving nutritional quality. RESULTS: We found no
association between plasma PCSK9 levels and body mass index, waist circumference,
fat and fat-free mass, or visceral and subcutaneous adipose tissue measured by
computed tomography. Compared to men with the lowest PCSK9 levels (bottom
tertile), those with the highest PCSK9 levels (top tertile) had the most
detrimental lipoprotein-lipid profile including lower LDL particle size (253.6 +/
4.0 vs. 251.6 +/- 4.0 A, p < 0.05) and higher apolipoprotein C-III levels (36.8
+/- 10.6 vs. 32.3 +/- 32.3, p < 0.05). These men were also characterized by
higher HOMA-IR indices (6.78 +/- 3.01 vs. 5.54 +/- 2.91, p < 0.05). After one
year, study participants lost on average 6.7 +/- 4.6 kg (p < 0.0001). Plasma
PCSK9 decreased by 9.2 +/- 53.7 ng/ml (3.8%, p = 0.07). CONCLUSIONS: Plasma PCSK9
levels are not associated with body fat distribution indices, modestly associated
with markers of insulin resistance and LDL particle size and are slightly
affected by a lifestyle modification program in abdominally obese men.
PMID- 25128758
TI - Osteopontin - a multi-modal marker and mediator in atherosclerotic vascular
disease.
AB - Atherosclerosis is a chronic inflammatory process of the vessel wall with
systemic correlates. It is now well established that patients' outcome is tightly
linked to atherosclerotic plaque stability, potentially more so than to the mere
plaque size. Osteopontin (OPN) is an integrin-binding ligand, N-linked
glycoprotein, which was recognized as a significant participant in the
atherosclerotic inflammatory milieu. Evidence from several genetic mouse models
suggests that OPN is an enhancer of atherosclerosis. This may be mediated by its
capacity to enhance inflammation in the atherosclerotic plaque. Interestingly,
OPN may also possess potentially protective vascular effects, such as attenuation
of vascular calcification. In humans circulating levels of OPN were found to be
independently associated with the severity of coronary atherosclerosis. Moreover,
several studies report that high plasma OPN levels were associated with increased
risk for major adverse cardiac events. This review aims to critically assess
current understanding of the role of OPN in the atherosclerotic process, from
animal models to clinical practice. Specific focus is given to evaluating whether
OPN could serve as a marker for monitoring coronary atherosclerosis severity, and
in parallel, assess the evidence for its role as a mediator in the pathogenic
pathways leading to atherosclerotic vascular disease.
PMID- 25128759
TI - Activated macrophages create lineage-specific microenvironments for pancreatic
acinar- and beta-cell regeneration in mice.
AB - BACKGROUND & AIMS: Although the cells that contribute to pancreatic regeneration
have been widely studied, little is known about the mediators of this process.
During tissue regeneration, infiltrating macrophages debride the site of injury
and coordinate the repair response. We investigated the role of macrophages in
pancreatic regeneration in mice. METHODS: We used a saporin-conjugated antibody
against CD11b to reduce the number of macrophages in mice following diphtheria
toxin receptor-mediated cell ablation of pancreatic cells, and evaluated the
effects on pancreatic regeneration. We analyzed expression patterns of
infiltrating macrophages after cell-specific injury or from the pancreas of
nonobese diabetic mice. We developed an in vitro culture system to study the
ability of macrophages to induce cell-specific regeneration. RESULTS: Depletion
of macrophages impaired pancreatic regeneration. Macrophage polarization, as
assessed by expression of tumor necrosis factor-alpha, interleukin 6, interleukin
10, and CD206, depended on the type of injury. The signals provided by polarized
macrophages promoted lineage-specific generation of acinar or endocrine cells.
Macrophage from nonobese diabetic mice failed to provide signals necessary for
beta-cell generation. CONCLUSIONS: Macrophages produce cell type-specific signals
required for pancreatic regeneration in mice. Additional study of these processes
and signals might lead to new approaches for treating type 1 diabetes or
pancreatitis.
PMID- 25128760
TI - Dual DNA-binding domains shape the interaction of Brh2 with DNA.
AB - Brh2, the BRCA2 ortholog in the fungus Ustilago maydis, harbors two different DNA
binding domains, one located in the N-terminal region and the other located in
the C-terminal region. Here we were interested in comparing the biochemical
properties of Brh2 fragments, Brh2(NT) and Brh2(CT), respectively, harboring the
two different DNA-binding regions to understand the mechanistic purpose of dual
DNA-interaction domains. With oligonucleotide substrates to model different DNA
conformations, it was found that the substrate specificity of Brh2(NT) and
Brh2(CT) was almost indistinguishable although avidity was different depending on
salt concentration. DNA annealing activity inherent in Brh2 was found to be
attributable to Brh2(NT). Likewise, activity responsible for a second-end capture
reaction modeling a later step in repair of DNA double-strand breaks was found
attributable to Brh2(NT). Efficient annealing of DNA strands coated with RPA
required full length Brh2 rather than Brh2(NT) suggesting Brh2(CT) contributes to
the activity when RPA is present. Brh2(NT) and Brh2(CT) were both found capable
of physically interacting with RPA. The results suggest that while the two DNA
binding regions of Brh2 appear functionally redundant in certain aspects of DNA
repair, they differ in fundamental properties, and likely contribute in different
ways to repair processes involving or arising from stalled DNA replication forks.
PMID- 25128761
TI - Remarkable induction of UV-signature mutations at the 3'-cytosine of dipyrimidine
sites except at 5'-TCG-3' in the UVB-exposed skin epidermis of xeroderma
pigmentosum variant model mice.
AB - The human POLH gene is responsible for the variant form of xeroderma pigmentosum
(XP-V), a genetic disease highly susceptible to cancer on sun-exposed skin areas,
and encodes DNA polymerase eta (poleta), which is specialized for translesion DNA
synthesis (TLS) of UV-induced DNA photolesions. We constructed poleta-deficient
mice transgenic with lacZ mutational reporter genes to study the effect of Polh
null mutation (Polh(-/-)) on mutagenesis in the skin after UVB irradiation. UVB
induced lacZ mutations with remarkably higher frequency in the Polh(-/-)
epidermis and dermis than in the wild-type (Polh(+/+)) and heterozygote. DNA
sequences of a hundred lacZ mutants isolated from the epidermis of four UVB
exposed Polh(-/-) mice were determined and compared with mutant sequences from
irradiated Polh(+)(/)(+) mice. The spectra of the mutations in the two genotypes
were both highly UV-specific and dominated by C->T transitions at dipyrimidines,
namely UV-signature mutations. However, sequence preferences of the occurrence of
UV-signature mutations were quite different between the two genotypes: the
mutations occurred at a higher frequency preferentially at the 5'-TCG-3' sequence
context than at the other dipyrimidine contexts in the Polh(+/+) epidermis,
whereas the mutations were induced remarkably and exclusively at the 3'-cytosine
of almost all dipyrimidine contexts with no preference for 5'-TCG-3' in the Polh(
/-) epidermis. In addition, in Polh(-/-) mice, a small but remarkable fraction of
G->T transversions was also observed exclusively at the 3'-cytosine of
dipyrimidine sites, strongly suggesting that these transversions resulted not
from oxidative damage but from UV photolesions. These results would reflect the
characteristics of the error-prone TLS functioning in the bypass of UV
photolesions in the absence of poleta, which would be mediated by mechanisms
based on the two-step model of TLS. On the other hand, the deamination model
would explain well the mutation spectrum in the Polh(+/+) genotype.
PMID- 25128763
TI - Isolation and characterization of plant growth-promoting rhizobacteria and their
effects on phytoremediation of petroleum-contaminated saline-alkali soil.
AB - This study aimed to isolate promising halotolerant and alkalotolerant plant
growth-promoting rhizobacteria and to study their effects on the growth of tall
fescue and phytodegradation efficiency in a petroleum-contaminated saline
alkaline soil. A total of 115 PGPR strains were isolated from the rhizosphere of
tall fescue grown in petroleum-contaminated saline-alkaline soils. Of these, 5
strains indicating 1-aminocyclopropane-l-carboxylic acid deaminase activity>1.0M
alpha-KB mg(-1)h(-1) were selected for further studies. The isolate D5A presented
the highest plant-growth-promoting activity and was identified as Klebsiella sp.
It grew well on the Luria-Bertani medium containing 9% NaCl and at a pH range of
4-10. A pot experiment was then conducted to study the effect of isolates on
phytoremediation. The results showed that inoculation of D5A promoted tall fescue
growth and enhanced remediation efficiency in petroleum-contaminated saline
alkaline soil.
PMID- 25128762
TI - Virus-host mucosal interactions during early SIV rectal transmission.
AB - To deepen our understanding of early rectal transmission of HIV-1, we studied
virus-host interactions in the rectal mucosa using simian immunodeficiency virus
(SIV)-Indian rhesus macaque model and mRNA deep sequencing. We found that rectal
mucosa actively responded to SIV as early as 3 days post-rectal inoculation (dpi)
and mobilized more robust responses at 6 and 10 dpi. Our results suggest that the
failure of the host to contain virus replication at the portal of entry is
attributable to both a high-level expression of lymphocyte chemoattractant,
proinflammatory and immune activation genes, which can recruit and activate viral
susceptible target cells into mucosa; and a high-level expression of SIV
accessory genes, which are known to be able to counter and evade host restriction
factors and innate immune responses. This study provides new insights into the
mechanism of rectal transmission.
PMID- 25128764
TI - Removal of CdTe in acidic media by magnetic ion-exchange resin: a potential
recycling methodology for cadmium telluride photovoltaic waste.
AB - Sulfonated magnetic microspheres (PSt-DVB-SNa MPs) have been successfully
prepared as adsorbents via an aqueous suspension polymerization of styrene
divinylbenzene and a sulfonation reaction successively. The resulting adsorbents
were confirmed by means of Fourier transform infrared spectra (FT-IR), X-ray
diffraction (XRD), transmission electron microscope (TEM), scanning electron
microscope equipped with an energy dispersive spectrometer (SEM-EDS) and
vibrating sample magnetometer (VSM). The leaching process of CdTe was optimized,
and the removal efficiency of Cd and Te from the leaching solution was
investigated. The adsorbents could directly remove all cations of Cd and Te from
a highly acidic leaching solution of CdTe. The adsorption process for Cd and Te
reached equilibrium in a few minutes and this process highly depended on the
dosage of adsorbents and the affinity of sulfonate groups with cations. Because
of its good adsorption capacity in strong acidic media, high adsorbing rate, and
efficient magnetic separation from the solution, PSt-DVB-SNa MPs is expected to
be an ideal material for the recycling of CdTe photovoltaic waste.
PMID- 25128765
TI - The lipid profile of brown adipose tissue is sex-specific in mice.
AB - Brown adipose tissue (BAT) is a thermogenic organ with a vital function in small
mammals and potential as metabolic drug target in humans. By using high
resolution LC-tandem-mass spectrometry, we quantified 329 lipid species from 17
(sub)classes and identified the fatty acid composition of all phospholipids from
BAT and subcutaneous and gonadal white adipose tissue (WAT) from female and male
mice. Phospholipids and free fatty acids were higher in BAT, while DAG and TAG
levels were higher in WAT. A set of phospholipids dominated by the residue
docosahexaenoic acid, which influences membrane fluidity, showed the highest
specificity for BAT. We additionally detected major sex-specific differences
between the BAT lipid profiles, while samples from the different WAT depots were
comparatively similar. Female BAT contained less triacylglycerol and more
phospholipids rich in arachidonic and stearic acid whereas another set of fatty
acid residues that included linoleic and palmitic acid prevailed in males. These
differences in phospholipid fatty acid composition could greatly affect
mitochondrial membranes and other cellular organelles and thereby regulate the
function of BAT in a sex-specific manner.
PMID- 25128766
TI - Increased oxidative DNA damage and decreased expression of base excision repair
proteins in airway epithelial cells of women who cook with biomass fuels.
AB - To investigate whether biomass burning causes oxidative DNA damage and alters the
expression of DNA base excision repair (BER) proteins in airway cells, sputum
samples were collected from 80 premenopausal rural biomass-users and 70 age
matched control women who cooked with liquefied petroleum gas. Compared with
control the airway cells of biomass-users showed increased DNA damage in alkaline
comet assay. Biomass-users showed higher percentage of cells expressing oxidative
DNA damage marker 8-oxoguanine and lower percentages of BER proteins OGG1 and
APE1 by immunocytochemical staining. Reactive oxygen species (ROS) generation was
doubled and level of superoxide dismutase was depleted significantly among
biomass-users. The concentrations of particulate matters were higher in biomass
using households which positively correlated with ROS generation and negatively
with BER proteins expressions. ROS generation was positively correlated with 8
oxoguanine and negatively with BER proteins suggesting cooking with biomass is a
risk for genotoxicity among rural women in their child-bearing age.
PMID- 25128767
TI - Increased expression and activation of serum- and glucocorticoid-inducible kinase
1 (SGK1) by cadmium in HK-2 renal proximal tubular epithelial cells.
AB - In HK-2 cells exposed to cadmium chloride (CdCl2), the level of serum- and
glucocorticoid-inducible kinase-1 (SGK1) protein is increased, but the levels of
SGK2 and SGK3 proteins are not. Phosphorylation of SGK1 protein is also observed.
Treatment with actinomycin D abolished CdCl2-induced elevation of SGK1 mRNA
level. Treatment with actinomycin D or cycloheximide suppressed SGK1 protein
levels in cells exposed to CdCl2. Treatment with SGK1 inhibitor EMD638683 or
knockdown of SGK1 with siRNA suppressed CdCl2-induced phosphorylation of N-Myc
downstream-regulated kinase 1 (NDRG1). These results indicate that cadmium
induces the transcriptional upregulation of SGK1 expression and regulates NDRG1
in HK-2 cells.
PMID- 25128768
TI - Morpho-physiological effects of ibuprofen on Scenedesmus rubescens.
AB - The pollution of aquatic bodies by drugs is an emerging environmental problem,
because of their extensive use in animal and human context. Ibuprofen, 2-[4-(2
methylpropyl)phenyl]propanoic acid, is the non-steroidal anti-inflammatory drug
mainly present both in wastewater and in rivers and lakes in Europe. Since in
literature there is little information about the effects of ibuprofen on
microalgae, in this paper we presented the results on the effects of this
molecule at different concentrations (62.5MUgL(-1), 250MUgL(-1) and 1000MUgL(-1))
on cultures of the freshwater microalga Scenedesmus rubescens (P.J.L. Dangeard)
E. Kesslet et al. Ibuprofen effects on the alga were assayed at first through
analyses of the growth curve. Moreover, analyses of cell morphology,
ultrastructure, and photosynthetic pigments were additionally performed. The
first negative effect of the drug was on the microalga growth, suggesting a drug
action dose-dependent mechanism type, more evident at the concentration of
1000MUgL(-1) ibuprofen and in the last phase of the growth curve. In support of
this, following ibuprofen exposure, the cells exhibited morphological and
ultrastructural alterations, mainly consisting in large cytoplasmic inclusions,
probably of lipids and/or carotenoids. The decrease of chlorophyll amounts and,
on the contrary, the increase of carotenoids were correlated with a stressful
condition induced by drug.
PMID- 25128769
TI - Arsenic decreases antinociceptive activity of paracetamol: possible involvement
of serotonergic and endocannabinoid receptors.
AB - We assessed whether repeated arsenic exposure can decrease paracetamol-mediated
antinociception by modulating serotonergic and endocannabinoid pathways. Rats
were preexposed to elemental arsenic (4ppm) as sodium arsenite through drinking
water for 28 days. Next day paracetamol's (400mg/kg, oral) antinociceptive
activity was assessed through formalin-induced nociception. Serotonin content and
gene expression of 5-HT1A, 5-HT2A and CB1 receptors were evaluated in brainstem
and frontal cortex. Arsenic decreased paracetamol-mediated analgesia.
Paracetamol, but not arsenic, increased serotonin content in these regions.
Arsenic attenuated paracetamol-mediated increase in serotonin level. Paracetamol
did not alter 5-HT1A expression, but caused down-regulation of 5-HT2A and up
regulation of CB1 receptors. Arsenic down-regulated these receptors. However,
paracetamol-mediated down-regulation of 5-HT2A was more pronounced. Arsenic did
not modify paracetamol's effect on 5-HT1A expression, but reduced paracetamol
mediated down-regulation of 5-HT2A and reversed up-regulation of CB1 receptors.
Results suggest arsenic reduced paracetamol-induced analgesia possibly by
interfering with pronociceptive 5-HT2A and antinociceptive CB1 receptors.
PMID- 25128770
TI - Chemical composition, anti-inflammatory activity and cytotoxic activity of the
liposoluble constituents from different parts of Acanthopanax evodiaefolius by
the Herbal Blitzkrieg Extractor.
AB - The liposoluble constituents of leaves (LCL) and stem barks (LCSB) from
Acanthopanax evodiaefolius Franch were extracted by Herbal Blitzkrieg Extractor
(HBE), and their chemical composition was analyzed by GC-MS. 18 compounds were
identified, representing 71.98% of LCL, while 35 compounds were identified,
accounting for 98.28% of the LCSB. Their cytotoxic activity and inhibitory effect
on nitric oxide (NO) production in LPS-stimulated RAW 264.7 cells were tested and
the LCL showed significant NO, IL-6 and TNF-alpha inhibition activity. These
results provide the scientific basis for looking for new natural anti
inflammatory substances and exploiting and developing resources of A.
evodiaefolius Franch.
PMID- 25128771
TI - Arsenic trioxide exerts a double effect on osteoblast growth in vitro.
AB - Arsenic trioxide (ATO) is a promising antitumor agent used to treat acute
promyelocytic leukemia (APL) and, recently solid tumor. The present study was
designed to evaluate the effect of ATO proliferation of osteoblast that plays
very important roles in maintaining the structure integrity and function of bone.
Cell survives, apoptosis, collagen, and molecular targets were identified by
multiple detecting techniques, including MTT assay, electron microscopy, collagen
detecting kit, TUNEL kit, and western blot in hFOB1.19 human osteoblasts cell
line. The results showed that low dose of ATO (0.25, 0.5, and 1MUM) remarkably
enhanced the viability of cultured osteoblasts in a concentration- and time
dependent manner. Intriguingly, a dual effect of high dose of ATO (5, 10, and
20MUM) was also observed showing significant reduction in viability of culture
osteoblasts at concentration- and time-dependent fashion. Moreover, low dose of
ATO promoted secretion and synthesis of collagen, whereas high dose of ATO
induced typical morphological characteristics of apoptosis in osteoblasts.
Mechanically, western blot results demonstrated that low dose of ATO dramatically
up-regulated TGF-beta1 protein and activated p-AKT proliferative signaling. And,
high dose of ATO increased Bax/Bcl-2 ratio in a time-dependent fashion and
activated caspase-3 apoptotic signaling. These results demonstrate at the first
time that ATO exerts a double effect on osteoblast function depending upon the
concentration and provide a clue to rationally use ATO for clinicians to pay more
attention to protect bone from the adverse effects of therapeutic dose of ATO
during tumor therapy.
PMID- 25128772
TI - Protective effect of naringenin against gentamicin-induced nephrotoxicity in
rats.
AB - The protective effect of naringenin, a flavonoid compound isolated from citrus
fruits, was investigated against nephrotoxicity induced by gentamicin (80mgkg(
1)/day, i.p., for eight days) in rats. Naringenin treatment (50mgkg(-1)/day,
p.o.) was administered for eight days, starting on the same day of gentamicin
administration. Gentamicin caused significant elevations of serum creatinine, and
kidney tissue levels of malondialdehyde, nitric oxide, and interleukin-8, and a
significant decrease in renal glutathione peroxidase activity. Naringenin
treatment significantly ameliorated the changes in the measured biochemical
parameters resulted from gentamicin administration. Also, naringenin markedly
attenuated the histopathological renal tissue injury observed with gentamicin.
Immunohistochemical examinations showed that naringenin significantly reduced the
gentamicin-induced expression of kidney injury molecule-1, vascular endothelial
growth factor, inducible nitric oxide synthase, and caspase-9, and increased
survivin expression in the kidney tissue. It was concluded that naringenin,
through its antioxidant and anti-inflammatory effects, may represent a
therapeutic option to protect against gentamicin nephrotoxicity.
PMID- 25128773
TI - Geochemical and grain-size distribution of radioactive and stable cesium in
Fukushima soils: implications for their long-term behavior.
AB - Availability and mobility of radioactive cesium, (137)Cs, in soils are crucial
for recovery from the accident in the Fukushima Dai-ichi Nuclear Power Plants. In
this study we investigated the geochemical and grain-size distribution of (137)Cs
in 11 soil samples collected in the eastern area of Fukushima Prefecture after
the accident. Sequential extractions were performed to evaluate the distribution
of (137)Cs having different geochemical interactions with soil components. The
result was further compared with that of the stable cesium, (133)Cs, which had
occurred in the soils before the accident. The distribution of (137)Cs in
different grain-size fractions was also determined. Radioactive cesium was
predominantly found in the extract obtained by strong-acid dissolution and the
extraction residue and was more concentrated in silt and clay grains. X-ray
diffraction analyses revealed that micaceous minerals as well as kaolin minerals
were predominantly dissolved by the strong-acid treatment. Correlation between
the fraction of (137)Cs and the content of micaceous minerals in different grain
size fractions of soil minerals suggests that micaceous minerals are responsible
for the fixation of (137)Cs in the soils. The isotopic ratio of (137)Cs and
(133)Cs in the extract by strong-acid dissolution was more than three times
smaller than those in the extracts by water, ion exchange, and reductive
dissolution. This indicates that the distribution of (137)Cs was not in the
steady state in 2 y after the accident due to relatively slow fixation by the
soil clay minerals.
PMID- 25128774
TI - High (36)Cl/Cl ratios in Chernobyl groundwater.
AB - After the explosion of the Chernobyl Nuclear Power Plant in April 1986,
contaminated material was buried in shallow trenches within the exclusion zone. A
(90)Sr plume was evidenced downgradient of one of these trenches, trench T22. Due
to its conservative properties, (36)Cl is investigated here as a potential tracer
to determine the maximal extent of the contamination plume from the trench in
groundwater. (36)Cl/Cl ratios measured in groundwater, trench soil water and leaf
leachates are 1-5 orders of magnitude higher than the theoretical natural
(36)Cl/Cl ratio. This contamination occurred after the Chernobyl explosion and
currently persists. Trench T22 acts as an obvious modern point source of (36)Cl,
however other sources have to be involved to explain such contamination. (36)Cl
contamination of groundwater can be explained by dilution of trench soil water by
uncontaminated water (rainwater or deep groundwater). With a plume extending
further than that of (90)Sr, radionuclide which is impacted by retention and
decay processes, (36)Cl can be considered as a suitable tracer of contamination
from the trench in groundwater provided that modern release processes of (36)Cl
from trench soil are better characterized.
PMID- 25128775
TI - Development of a model using the MATLAB System identification toolbox to estimate
(222)Rn equilibrium factor from CR-39 based passive measurements.
AB - Can and Bare method is a widely used passive method for measuring the equilibrium
factor F through the determination of the track density ratio between bare (D)
and filtered (Do) detectors. The dimensions of the used diffusion chamber are
altering the deposition ratios of Po-isotopes on the chamber walls as well as the
ratios of the existing alpha emitters in air. Then the measured filtered track
density and therefore the resultant equilibrium factor is changed according to
the diffusion chamber dimensions. For this reason, high uncertainty was expected
in the measured F using different diffusion chambers. In the present work, F is
derived as a function of both track density ratio (D/Do) and the dimensions of
the used diffusion chambers (its volume to the total internal surface area; V/A).
The accuracy of the derived formula was verified using the black-box modeling
technique via the MATLAB System identification toolbox. The results show that the
uncertainty of the calculated F by using the derived formula of F (D/Do, V/A) is
only 5%. The obtained uncertainty ensures the quality of the derived function to
calculate F using diffusion chambers with wide range of dimensions.
PMID- 25128776
TI - Total contents of arsenic and associated health risks in edible mushrooms,
mushroom supplements and growth substrates from Galicia (NW Spain).
AB - The levels of arsenic (As) in the main commercial species of mushrooms present in
Galicia, in their growth substrates, and mushroom supplements have been analysed
by ICP-MS, with the intention of assessing potential health risks involved with
their consumption. The mean concentrations of As in wild and cultivated mushrooms
was 0.27mg/kg dw, in mushroom supplements 0.40mg/kg dw, in soils 5.10mg/kg dw,
and in growth substrate 0.51mg/kg dw. No significant differences were observed
between species, although the species Lactarius deliciosus possessed a slightly
more elevated mean concentration (at 0.49mg/kg dw) than the other species
investigated. In soils, statistically significant differences (p<0.05) were
observed according to geographic origin. Levels in mushroom supplements, although
low, were higher than in wild or cultivated mushrooms. Measured arsenic levels
were within the normal range in samples analysed in unpolluted areas. Because of
the low As concentrations found in fungi and mushroom supplements from Galicia,
and considering the relatively small inclusion of these foods in people's diet,
it can be concluded that there is no toxicological risk of arsenic associated
with the consumption of the species of mushrooms analysed or at the dosages
indicated for mushroom supplements.
PMID- 25128777
TI - Outcome and surgical management for geriatric traumatic brain injury: analysis of
888 cases registered in the Japan Neurotrauma Data Bank.
AB - OBJECTIVE: As the aged population is rapidly growing globally, geriatric
traumatic brain injury (TBI) becomes an increasing problem. There are higher
mortality and poorer functional outcome in the geriatric TBI population (>=65
years) compared with younger groups despite neurosurgical interventions.
Therefore, current treatment priorities and cost-effectiveness should be
critically examined. We evaluated the benefit of surgical management in the
elderly (>=65 years) after TBI. METHODS: A total of 3194 patients with confirmed
TBI were enrolled from 1998 to 2011, in the Japan Neurotrauma Data Bank.
Retrospective analysis was conducted from the Japan Neurotrauma Data Bank on 888
(28%) patients (>=65 years) who did and did not undergo surgery. In particular,
the effect of low Glasgow coma scale (GCS) (3-5) was compared with outcome with
and without surgery. RESULTS: Of all the patients 65 years of age and over, 478
(54%) were given surgical management (craniectomy, craniotomy, or burr-hole
evacuation). This group of patients had significantly more favorable outcome at 6
months (18% vs. 7%) and less mortality (62% vs. 81%). However, within this
surgical group, patients with initial GCS scores of 3-5 had significantly more
unfavorable outcome (96% vs. 79%) and more mortality (87% vs. 57%) compared with
those with GCS scores of 6-15. CONCLUSIONS: We confirmed that age is a major
determinant of outcome after TBI. In addition, we found that neurosurgical
management is associated with the improvement of the prognosis and a decrease in
the rate of mortality in geriatric TBI. However, surgical management was not
shown to be an effective treatment in elderly patients with GCS scores of 3-5.
PMID- 25128778
TI - Evidence for the light hole in GaAs/AlGaAs quantum wells from optically-pumped
NMR and Hanle curve measurements.
AB - Optically-pumped (69)Ga NMR (OPNMR) and optically-detected measurements of
polarized photoluminescence (Hanle curves) show a characteristic feature at the
light hole-to-conduction band transition in a GaAs/AlxGa1-xAs multiple quantum
well sample. OPNMR data are often depicted as a "profile" of the OPNMR integrated
signal intensity plotted versus optical pumping photon energy. What is notable is
the inversion of the sign of the measured (69)Ga OPNMR signals when optically
pumping this light hole-to-conduction band energy in OPNMR profiles at multiple
external magnetic fields (B0=4.7T and 3T) for both sigma(+) and sigma(-)
irradiation. Measurements of Hanle curves at B0=0.5T of the same sample exhibit
similar phase inversion behavior of the Hanle curves at the photon energy for
light hole excitation. The zero-field value of the light-hole state in the
quantum well can be predicted for the quantum well structure using the positions
of each of these signal-inversion features, and the spin splitting term in the
equation for the transition energy yields consistent values at 3 magnetic fields
for the excitonic g-factor (g(ex)). This study demonstrates the application of
OPNMR and optical measurements of the photoluminescence to detect the light hole
transition in semiconductors.
PMID- 25128779
TI - Heteronuclear transverse and longitudinal relaxation in AX4 spin systems:
application to (15)N relaxations in (15)NH4(+).
AB - The equations that describe the time-evolution of transverse and longitudinal
(15)N magnetisations in tetrahedral ammonium ions, (15)NH4(+), are derived from
the Bloch-Wangsness-Redfield density operator relaxation theory. It is assumed
that the relaxation of the spin-states is dominated by (1) the intra-molecular
(15)N-(1)H and (1)H-(1)H dipole-dipole interactions and (2) interactions of the
ammonium protons with remote spins, which also include the contribution to the
relaxations that arise from the exchange of the ammonium protons with the bulk
solvent. The dipole-dipole cross-correlated relaxation mechanisms between each of
the (15)N-(1)H and (1)H-(1)H interactions are explicitly taken into account in
the derivations. An application to (15)N-ammonium bound to a 41kDa domain of the
protein DnaK is presented, where a comparison between experiments and simulations
show that the ammonium ion rotates rapidly within its binding site with a local
correlation time shorter than approximately 1ns. The theoretical framework
provided here forms the basis for further investigations of dynamics of AX4 spin
systems, with ammonium ions in solution and bound to proteins of particular
interest.
PMID- 25128780
TI - Neighbourhood availability of alcohol outlets and hazardous alcohol consumption
in New Zealand.
AB - The socio-spatial arrangement of alcohol retailers is potentially important in
understanding the relationship between neighbourhood context and 'excessive'
alcohol consumption. This New Zealand study examines whether the availability of
alcohol products is associated with individual-level alcohol consumption.
Measures capturing the availability of alcohol retailers were calculated for
neighbourhoods across the country and then appended to a national health survey.
At the national level there was no evidence for an association between hazardous
consumption and alcohol outlet access. However, there was evidence of
associations with neighbourhood retailing for younger Maori and Pacific peoples
males; younger European females; middle-aged European men; and older men. The
findings provide evidence that 'alcogenic' environments are associated with
excessive drinking in New Zealand, albeit that the associations are restricted to
particular vulnerable groups.
PMID- 25128781
TI - Modulation of dendritic cell antigen presentation by pathogens, tissue damage and
secondary inflammatory signals.
AB - Antigen presentation by dendritic cells (DC) is regulated directly by pathogen
associated or cell death-associated cues, or indirectly by immunomodulatory
molecules produced during infection or tissue damage. DC modulation by direct
encounter of pathogen-associated compounds has been thoroughly studied; the
effects of molecules associated with cell death are less well characterized;
modulation by secondary signals remain poorly understood. In this review we
describe recent studies on the role of these three categories of immunomodulatory
compounds on DC. We conclude that characterization of the role of secondary
immunomodulators is an area in dare need of further study. The outcomes of this
endeavor will be new opportunities for the development of better vaccines and
compounds applicable to the therapeutic immunomodulation of DC function.
PMID- 25128782
TI - Eosinophils as a pharmacological target for the treatment of allergic diseases.
AB - Eosinophils are innate immune cells and active players in inflammatory responses.
Their activation and increased levels in the blood and at specific sites are
associated with parasitic infections and several inflammatory conditions, notably
allergic diseases in which eosinophils are considered to be damaging cells.
Intervention targeting eosinophils is thought to prevent and/or limit
irreversible organ damage and other eosinophil-associated disorders like
hypereosinophilic syndromes, some cancers and autoimmune diseases. Several
eosinophil-targeted therapeutic agents which block specific steps in eosinophil
differentiation, migration and activation have recently been developed, showing
encouraging results and new insights into their specific role in allergy. Here,
we review some potentially effective drug compounds, their drawbacks and future
prospective focusing on allergic diseases.
PMID- 25128784
TI - Carvedilol protects the infarcted heart by upregulating miR-133: first evidence
that disease state affects beta-adrenergic arrestin-biased signaling?
PMID- 25128783
TI - Upregulation of functional Kv11.1 isoform expression by inhibition of intronic
polyadenylation with antisense morpholino oligonucleotides.
AB - The KCNH2 gene encodes the Kv11.1 potassium channel that conducts the rapidly
activating delayed rectifier current in the heart. KCNH2 pre-mRNA undergoes
alternative processing; intron 9 splicing leads to the formation of a functional,
full-length Kv11.1a isoform, while polyadenylation within intron 9 generates a
non-functional, C-terminally truncated Kv11.1a-USO isoform. The relative
expression of Kv11.1 isoforms plays an important role in the regulation of Kv11.1
channel function and the pathogenesis of long QT syndrome. In this study, we
identified cis-acting elements that are required for KCNH2 intron 9 poly(A)
signal activity. Mutation of these elements decreased Kv11.1a-USO expression and
increased the expression of Kv11.1a mRNA, protein and channel current. More
importantly, blocking these elements by antisense morpholino oligonucleotides
shifted the alternative processing of KCNH2 intron 9 from the polyadenylation to
the splicing pathway, leading to the predominant production of Kv11.1a and a
significant increase in Kv11.1 current. Our findings indicate that the expression
of the Kv11.1a isoform can be upregulated by an antisense approach. Antisense
inhibition of KCNH2 intronic polyadenylation represents a novel approach to
increase Kv11.1 channel function.
PMID- 25128785
TI - Different tobacco retrotransposons are specifically modulated by the elicitor
cryptogein and reactive oxygen species.
AB - Interactions of plant retrotransposons with different steps of biotic and abiotic
stress-associated signaling cascades are still poorly understood. We perform here
a finely tuned comparison of four tobacco retrotransposons (Tnt1, Tnt2, Queenti,
and Tto1) responses to the plant elicitor cryptogein. We demonstrate that basal
transcript levels in cell suspensions and plant leaves as well as the activation
during the steps of defense signaling events are specific to each
retrotransposon. Using antisense NtrbohD lines, we show that NtrbohD-dependent
reactive oxygen species (ROS) production might act as negative regulator of
retrotransposon activation.
PMID- 25128786
TI - Assessment of candidate reference genes for the expression studies with
brassinosteroids in Lolium perenne and Triticum aestivum.
AB - Quantitative PCR studies need proper reference genes with expression stability
exclusively validated under certain experimental conditions. The expression
stability of several genes commonly used as references was tested under 24
epibrassinolide (EBR) and temperature treatment. Different statistical approaches
(qBase(PLUS), BestKeeper, NormFinder) were used to prepare rankings of expression
stability in two species of an economic importance: common wheat (Triticum
aestivum) and perennial ryegrass (Lolium perenne). Candidate reference genes were
shown to be regulated differentially in these two plant species. The maximum
stability values indicated that the expression stability was higher in T.
aestivum. Taking into account of all ranks it seems that TBP-1 and UBI in
ryegrass and ACT, ADP and EF1A in wheat should be used as reference genes in the
brassinosteroids and temperature involving studies.
PMID- 25128787
TI - Responses of a rice-field cyanobacterium Anabaena siamensis TISTR-8012 upon
exposure to PAR and UV radiation.
AB - The effects of PAR and UV radiation and subsequent responses of certain
antioxidant enzymatic and non-enzymatic defense systems were studied in a rice
field cyanobacterium Anabaena siamensis TISTR 8012. UV radiation resulted in a
decline in growth accompanied by a decrease in chlorophyll a and photosynthetic
efficiency. Exposure of cells to UV radiation significantly affected the
differentiation of vegetative cells into heterocysts or akinetes. UV-B radiation
caused the fragmentation of the cyanobacterial filaments conceivably due to the
observed oxidative stress. A significant increase of reactive oxygen species in
vivo and DNA strand breaks were observed in UV-B exposed cells followed by those
under UV-A and PAR radiation, respectively. The UV-induced oxidative damage was
alleviated due to an induction of antioxidant enzymatic/non-enzymatic defense
systems. In response to UV irradiation, the studied cyanobacterium exhibited a
significant increase in antioxidative enzyme activities of superoxide dismutase,
catalase and peroxidase. Moreover, the cyanobacterium also synthesized some UV
absorbing/screening substances. HPLC coupled with a PDA detector revealed the
presence of three compounds with UV-absorption maxima at 326, 331 and 345 nm. The
induction of the biosynthesis of these UV-absorbing compounds was found under
both PAR and UV radiation, thus suggesting their possible function as an active
photoprotectant.
PMID- 25128788
TI - Phonological, temporal and spectral processing in vowel length discrimination is
impaired in German primary school children with developmental dyslexia.
AB - It is still unclear whether phonological processing deficits are the underlying
cause of developmental dyslexia, or rather a consequence of basic auditory
processing impairments. To avoid methodological confounds, in the current study
the same task and stimuli of comparable complexity were used to investigate both
phonological and basic auditory (temporal and spectral) processing in dyslexia.
German dyslexic children (Grades 3 and 4) were compared to age- and grade-matched
controls in a vowel length discrimination task with three experimental
conditions: In a phonological condition, natural vowels were used, differing both
with respect to temporal and spectral information (in German, vowel length is
phonemic, and vowel length differences are characterized by both temporal and
spectral information). In a temporal condition, spectral information
differentiating between the two vowels of a pair was eliminated, whereas in a
spectral condition, temporal differences were removed. As performance measure,
the sensitivity index d' was computed. At the group level, dyslexic children's
performance was inferior to that of controls for phonological as well as temporal
and spectral vowel length discrimination. At an individual level, nearly half of
the dyslexic sample was characterized by deficits in all three conditions, but
there were also some children showing no deficits at all. These results reveal on
the one hand that phonological processing deficits in dyslexia may stem from
impairments in processing temporal and spectral information in the speech signal.
On the other hand they indicate, however, that not all dyslexic children might be
characterized by phonological or auditory processing deficits.
PMID- 25128789
TI - Contrasting deficits on executive functions in Chinese delinquent adolescents
with attention deficit and hyperactivity disorder symptoms and/or reading
disability.
AB - Many studies reported high prevalence of reading disability (RD) and attention
deficit hyperactivity disorder (ADHD) among delinquent adolescents. Very few have
examined their cognitive profile. The present study compared the executive
functions (EFs) and severity of delinquency in delinquent adolescents with RD
and/or ADHD symptoms (AS). Delinquents with AS (n=29), RD (n=24), comorbidity
AS+RD (n=35) were recruited from juvenile institutions along with typically
developing controls (n=29) from local schools; all completed EF assessments and
self-report questionnaires on delinquency. Results showed that pure AS group
exhibited impaired inhibition while the pure RD group was weak in processing
speed and visual memory. The comorbidity group showed unique impairments in
interference control and significantly higher delinquency severity. The present
findings suggest that comorbidity AS+RD may influence delinquency severity. It
also provides a more comprehensive picture of the unique EF deficits associated
with different groups, allowing for better matching for future identification and
intervention programme.
PMID- 25128790
TI - Memory failures for everyday tasks in caregivers of children with autism.
AB - The stress of caring for a loved one with chronic illness has been linked with
impairments in cognitive processes such as attention and problem solving, though
few studies have examined the impact on memory. Compromised cognition, in
particular, aspects of everyday functioning such as remembering medical
instructions and appointments, might affect caregivers' ability to maintain the
consistency and quality of care needed by the child. A sample of 31 caregivers of
children with autism and 51 parents of neuro-typical children completed an
electronic survey assessing their levels of psychological distress and everyday
memory. Perceived stress scores were higher in the caregiver group, as were self
reported memory failures for everyday tasks. The negative impact of caregiver
stress on everyday memory was particularly salient among caregivers experiencing
higher perceived levels of stress. These findings have implications for
interventions that aim to improve caregivers' cognitive well being through
targeting the psychological sequelae associated with the caregiving experience.
PMID- 25128793
TI - Explaining prompts children to privilege inductively rich properties.
AB - Four experiments with preschool-aged children test the hypothesis that engaging
in explanation promotes inductive reasoning on the basis of shared causal
properties as opposed to salient (but superficial) perceptual properties. In
Experiments 1a and 1b, 3- to 5-year-old children prompted to explain during a
causal learning task were more likely to override a tendency to generalize
according to perceptual similarity and instead extend an internal feature to an
object that shared a causal property. Experiment 2 replicated this effect of
explanation in a case of label extension (i.e., categorization). Experiment 3
demonstrated that explanation improves memory for clusters of causally relevant
(non-perceptual) features, but impairs memory for superficial (perceptual)
features, providing evidence that effects of explanation are selective in scope
and apply to memory as well as inference. In sum, our data support the proposal
that engaging in explanation influences children's reasoning by privileging
inductively rich, causal properties.
PMID- 25128792
TI - Is it or isn't it: listeners make rapid use of prosody to infer speaker meanings.
AB - A visual world experiment examined the time course for pragmatic inferences
derived from visual context and contrastive intonation contours. We used the
construction It looks like an X pronounced with either (a) a H(*) pitch accent on
the final noun and a low boundary tone, or (b) a contrastive L+H(*) pitch accent
and a rising boundary tone, a contour that can support contrastive inference
(e.g., It LOOKSL+H*like a zebraL-H%... (but it is not)). When the visual display
contained a single related set of contrasting pictures (e.g. a zebra vs. a zebra
like animal), effects of LOOKSL+H* emerged prior to the processing of phonemic
information from the target noun. The results indicate that the prosodic
processing is incremental and guided by contextually-supported expectations.
Additional analyses ruled out explanations based on context-independent
heuristics that might substitute for online computation of contrast.
PMID- 25128791
TI - Administration of the nicotinic acetylcholine receptor agonists ABT-089 and ABT
107 attenuates the reinstatement of nicotine-seeking behavior in rats.
AB - Current smoking cessation pharmacotherapies have modest efficacy, and most
smokers relapse within the first few days after a quit attempt. Nicotine
withdrawal-induced craving and cognitive impairments predict smoking relapse
during abstinence and suggest that cognitive-enhancing drugs may prevent relapse.
ABT-089 and ABT-107 are subtype-selective nAChR agonists that improve cognitive
performance in laboratory animals. However, there are no studies examining the
effects of ABT-089 and ABT-107 on nicotine self-administration and the
reinstatement of nicotine-seeking behavior, an animal model of relapse in human
smokers. The goal of the present study was to determine the effects of the
alpha4beta2*/alpha6beta2* nAChR agonist ABT-089 and the alpha7 nAChR agonist ABT
107 on nicotine taking and seeking in rats. The effects of acute ABT-089 and ABT
107 pretreatment on nicotine self-administration and reinstatement were tested in
male Sprague Dawley rats. Parallel studies of ABT-089 and ABT-107 on sucrose self
administration and reinstatement were tested in separate groups of rats to
determine if the effects of these drug treatments generalized to other reinforced
behaviors. Nicotine and sucrose self-administration behaviors were not altered
following acute administration of ABT-089 (0, 0.12, 1.2 and 12.0mg/kg) or ABT-107
(0, 0.03 and 0.3mg/kg). In contrast, both ABT-089 and ABT-107 pretreatment dose
dependently attenuated nicotine reinstatement. These effects were reinforcer
specific as no effects of ABT-089 or ABT-107 pretreatment on sucrose seeking were
noted. Taken together, these findings suggest that ABT-089 and ABT-107 do not
affect nicotine consumption, but may reduce the likelihood that a smoking lapse
will lead to relapse.
PMID- 25128794
TI - Examining the costs and benefits of inhibition in memory retrieval.
AB - Inhibitory control is thought to serve an adaptive function in controlling
behavior, with individual differences predicting variation in numerous cognitive
functions. However, inhibition is more properly construed as inducing both
benefits and costs to performance. Benefits arise at the point when inhibition
prevents expression of an unwanted or contextually inappropriate response; costs
arise later, when access to the inhibited representation is required by other
processes. Here we illustrate how failure to consider both the costs and benefits
of inhibition has generated confusion in the literature on individual differences
in cognitive control. Using retrieval-induced forgetting as a model case, we
illustrate this by showing that changing the way that retrieval-induced
forgetting is measured to allow greater expression of the benefits of inhibition
together with the costs can reduce and even reverse the theoretically predicted
correlation between motor and memory inhibition. Specifically, we show that when
the final test in a retrieval-induced forgetting procedure employs item-specific
cues (i.e., category-plus-stem cued recall and item-recognition) that better
isolate the lingering costs of inhibition, better motor response inhibition
(faster stop-signal reaction times) predicts greater retrieval-induced
forgetting. In striking contrast, when the final test is less well controlled,
allowing both the costs and benefits of inhibition to contribute, motor response
inhibition has the opposite relationship with retrieval-induced forgetting. These
findings underscore the importance of considering the correlated costs and
benefits problem when studying individual differences in inhibitory control. More
generally, they suggest that a shared inhibition mechanism may underlie people's
ability to control memories and actions.
PMID- 25128795
TI - Building phrases in language production: an MEG study of simple composition.
AB - Although research on language production has developed detailed maps of the brain
basis of single word production in both time and space, little is known about the
spatiotemporal dynamics of the processes that combine individual words into
larger representations during production. Studying composition in production is
challenging due to difficulties both in controlling produced utterances and in
measuring the associated brain responses. Here, we circumvent both problems using
a minimal composition paradigm combined with the high temporal resolution of
magnetoencephalography (MEG). With MEG, we measured the planning stages of simple
adjective-noun phrases ('red tree'), matched list controls ('red, blue'), and
individual nouns ('tree') and adjectives ('red'), with results indicating
combinatorial processing in the ventro-medial prefrontal cortex (vmPFC) and left
anterior temporal lobe (LATL), two regions previously implicated for the
comprehension of similar phrases. These effects began relatively quickly (~180
ms) after the presentation of a production prompt, suggesting that combination
commences with initial lexical access. Further, while in comprehension, vmPFC
effects have followed LATL effects, in this production paradigm vmPFC effects
occurred mostly in parallel with LATL effects, suggesting that a late process in
comprehension is an early process in production. Thus, our results provide a
novel neural bridge between psycholinguistic models of comprehension and
production that posit functionally similar combinatorial mechanisms operating in
reversed order.
PMID- 25128796
TI - Perception of tones by infants learning a non-tone language.
AB - This article examines the perception of tones by non-tone-language-learning (non
tone-learning) infants between 5 and 18 months in a study that reveals infants'
initial sensitivity to tonal contrasts, deterioration yet plasticity of tonal
sensitivity at the end of the first year, and a perceptual rebound in the second
year. Dutch infants in five age groups were tested on their ability to
discriminate a tonal contrast of Mandarin Chinese as well as a contracted tonal
contrast. Infants are able to discriminate tonal contrasts at 5-6 months, and
their tonal sensitivity deteriorates at around 9 months. However, the sensitivity
rebound sat 17-18 months. Non-tone-learning infants' tonal perception is elastic,
as is shown by the influence of acoustic salience and distributional learning:
(1) a salient contrast may remain discriminable throughout infancy whereas a less
salient one does not; (2) a bimodal distribution in tonal exposure increases non
tone-learning infants' discrimination ability during the trough in sensitivity to
tonal contrasts at 11-12 months. These novel findings reveal non-tone-learning
infants' U-shaped pattern in tone perception, and display their perceptual
flexibility.
PMID- 25128797
TI - On predicting others' words: electrophysiological evidence of prediction in
speech production.
AB - The present study investigated whether lexical processes that occur when we name
objects can also be observed when an interaction partner is naming objects. We
compared the behavioral and electrophysiological responses of participants
performing a conditional go/no-go picture naming task in two different
conditions: individually and jointly with a confederate participant. To obtain an
index of lexical processing, we manipulated lexical frequency, so that half of
the pictures had corresponding names of high-frequency and the remaining half had
names of low-frequency. Color cues determined whether participants should
respond, whether their task-partner should respond, or whether nobody should
respond. Behavioral and ERP results showed that participants engaged in lexical
processing when it was their turn to respond. Crucially, ERP results on no-go
trials revealed that participants also engaged in lexical processing when it was
their partner's turn to act. In addition, ERP results showed increased response
inhibition selectively when it was the partner's turn to act. These findings
provide evidence for the claim that listeners generate predictions about
speakers' utterances by relying on their own action production system.
PMID- 25128798
TI - Distributional learning has immediate and long-lasting effects.
AB - Evidence of distributional learning, a statistical learning mechanism centered on
relative frequency of exposure to different tokens, has mainly come from short
term learning and therefore does not ostensibly address the development of
important learning processes. The present longitudinal study examines both short-
and long-term effects of distributional learning of phonetic categories on non
native sound discrimination over a 12-month period. Two groups of listeners were
exposed to a two-minute distribution of auditory stimuli in which the most
frequently presented tokens either approximated or exaggerated the natural
production of the speech sounds, whereas a control group listened to a piece of
classical music for the same length of time. Discrimination by listeners in the
two distribution groups improved immediately after the short exposure,
replicating previous results. Crucially, this improvement was maintained after
six and 12 months, demonstrating that distributional learning has long-lasting
effects.
PMID- 25128799
TI - Alerting enhances attentional bias for salient stimuli: evidence from a
global/local processing task.
AB - The present study examined the role of alerting in modulating attentional bias to
salient events. In a global/local processing task, participants were presented
with a large arrow (global level) comprised of smaller arrows (local level)
pointing in the same or opposite directions and had to indicate the direction of
the large or small arrows in different blocks. Saliency of the global and local
levels was manipulated, creating global-salient and local-salient conditions.
Alerting signals were presented in half of the trials prior to the target.
Results revealed a double dissociation in the effects of alerting on global/local
interference effects. In a global salient condition, alerting increased global
interference and decreased local interference. In a local salient condition,
alerting reduced global interference and increased local interference. We
demonstrate that within a single task, alerting can increase and reduce conflict
based on perceptual saliency. These findings help to better understand disorders
like hemispatial neglect in which both arousal and attention to salient events
are impaired. These results also challenge previous theories suggesting that
alerting acts to increase conflict interference. We argue that alerting is an
adaptive mechanism that diverts attention to salient events, but comes at a cost
when selective attention to less salient details is required.
PMID- 25128800
TI - In vitro anti-leishmanial efficacy of potato tuber extract (PTEx): leishmanial
serine protease(s) as putative target.
AB - Leishmaniasis, a neglected tropical disease (NTD) causes major health problems in
the tropical and subtropical world. Most of the antileishmanial modern therapies
with different formulations of pentavalent antimonials, Miltefosine, Amphotericin
B etc. are not satisfactory in recent times due to high toxicity to the host and
present rising strain resistance issues. So there is an urgent need to develop
new, safe and cost-effective drugs against leishmaniasis. In this regard,
bioactive phytocomponents may lead to the discovery of new medicines with
appropriate efficiency. The prominent roles played by Leishmania proteases in the
virulence of this parasite make them very promising targets for the development
of current therapeutics of leishmaniasis. As part of a search for novel drugs, we
have evaluated in vitro anti-leishmanial activity of serine protease inhibitor
rich fraction (PTEx) obtained from potato tuber. The extract (PTEx) was prepared
by sodium bisulfite fractionation and inhibitors were identified by reverse
zymography. Inhibition study of PTEx in gelatin-zymogram and spectrophotometric
assay using BApNA and BTpNA as substrate reveal its strong inhibitory activity
against trypsin as well as serine proteases present in cell lysate of Leishmania
donovani infective strain. The in vitro MTT based colorimetric assay as well as
ex vivo L. donovani infected macrophages showed reduced parasite viability and
intracellular parasite load with IC50 = 312.5 +/- 0.1 MUg/ml and IC50 82.3 +/-
0.2 MUg/ml of PTEx respectively in a concentration dependent manner. This anti
leishmanial effect was also preceded by PTEx induced acute formation of ROS and
prolonged NO generation. The PTEx has no significant cytotoxic effect on host
macrophages. So taken together, these findings indicate that PTEx has promising
leishmanicidal effect and thus this study provides a new perspective of natural
serine protease inhibitor from potato tuber on the development of new drug
against leishmaniasis.
PMID- 25128801
TI - The potential of quinoline derivatives for the treatment of Toxoplasma gondii
infection.
AB - Here we reported our investigation, as part of our drug repositioning effort, on
anti-Toxoplasma properties of newly synthesized quinoline compounds. A collection
of 4-aminoquinoline and 4-piperazinylquinoline analogs have recently been
synthesized for use in cancer chemotherapy. Some analogs were able to outperform
chloroquine, a quinoline derivative drug which is commonly used in the treatment
of malaria and other parasitic infections. Herein 58 compounds containing one or
two quinoline rings were examined for their effectiveness as potential anti
Toxoplasma compounds. Of these 58 compounds, 32 were efficient at inhibiting
Toxoplasma growth (IC50<100 MUM). Five compounds with single and simple quinoline
rings exhibited similar cLogP values of ~2 and IC50 values between 5 and 6 MUM,
with one exception of 8-hydroxyquinoline whose IC50 value was 213 nM. The
addition of one hydroxyl group at position 8 caused a 40-fold increase in the
inhibitory effect of quinoline. A significant improvement in anti-Toxoplasma
effect among quinoline derivatives was detected in B11, B12, B23, and B24, whose
structures carry two quinoline rings, and their resultant cLogP values are ?7.
Among these compounds, B23 was the most effective compound with IC50 value of
425+/-35 nM, and TI value of 4.9. It was also noted that compounds with at least
one quinoline ring, displaying anti-Toxoplasma effects were capable of causing
the disappearance of the apicoplast, a plastid-like organelle. When treated with
quinoline, 8-hydroxyquinoline or B23, 40-45% of the parasites lost their
apicoplasts. Our findings recapitulate the properties of quinoline derivatives in
diminishing apicoplast. This could aid further investigations of anti-parasitic
treatments specific to Apicomplexan. More importantly, B12 and B23 which harbor
superior anti-cancer properties than chloroquine, have effective anti-Toxoplasma
activity. These compounds therefore have significant potential for future
development of chemotherapeutic agents for patients suffering from breast cancers
and parasitic infection.
PMID- 25128802
TI - Intranasal seasonal influenza vaccine and a TLR-3 agonist, rintatolimod, induced
cross-reactive IgA antibody formation against avian H5N1 and H7N9 influenza HA in
humans.
AB - The intranasal use of rintatolimod, a specific TLR-3 agonist, combined with
trivalent seasonal influenza vaccine generated cross-protection against highly
pathogenic H5N1 avian influenza in mice. The purpose of this clinical trial is to
assess the safety and impact of rintatolimod on intranasal influenza vaccine in
healthy adults. During Stage I of this Phase I/II clinical trial, 12 volunteers
were immunized intranasally with 3 doses of FluMist seasonal influenza vaccine on
Days 0, 28, and 56 followed by intranasal rintatolimod (50 MUg, 200 MUg, or 500
MUg) 3 days later. Parotid saliva and nasal wash samples were collected at
baseline and on Days 25, 53, 84, and 417. The samples were tested for IgA and IgG
specific antibodies (Ab) directed against the homologous FluMist viral
hemagglutinins (HAs). In addition, viral specific responses against influenza A
HAs were tested for IgA Ab cross-reactivity against 3 H5 clades: HA (H5N1)
A/Indonesia/5/2005, HA (H5N1) A/Hong Kong/483/97 and HA (H5N1)
A/Vietnam/1194/2004, as well as, two H7 strains, HA (H7N9) A/Shanghai/2/2013 and
HA (H7N3) A/chicken/Jalisco/CPA1. The combination of the intranasal FluMist along
with the rintatolimod generated specific secretory IgA responses of at least 4
fold over baseline against at least one of the homologous vaccine strains
included in the vaccine in 92% of the vaccinees. Additionally, this vaccination
strategy induced cross-reactive secretory IgA against highly pathogenic avian
influenza virus strains H5N1, H7N9, and H7N3 with pandemic potential for humans.
The combination of rintatolimod and FluMist was well-tolerated.
PMID- 25128803
TI - Pneumococcal vaccination in people living with HIV.
AB - Streptococcus pneumoniae is the leading bacterial opportunistic infection (OI) in
HIV positive individuals. Anti-retroviral treatment (ART) reduces their risk of
Invasive Pneumococcal Disease (IPD), however, it remains 20- to 40-fold greater
than that of the general population. In HIV-infected adults, pneumococcal
vaccination (PCV) induces more durable and functional antibody responses in
individuals on ART at the time of vaccination than in ART-naive adults,
independently of the baseline CD4+ cell count. National guidelines in the UK
recommend vaccination in HIV-infected adults with CD4 count >200cells/mL and
advise that it be considered for those with CD4 count <200cells/mL(3). We report
data on IPD from a London HIV cohort of 3500 north-east London patients from 2009
to 2012. IPD was defined as a positive pneumococcal culture from blood, CSF,
joint aspirate or pericardial fluid. HIV positive cases were identified by cross
referencing hospital identifiers with a positive HIV Ab/Ag test result or HIV
viral load test result on the virology database. There were a total 189 cases of
Invasive Pneumococcal Disease identified over the three years. 4.8% (n=9) were
known to be HIV positive at the time of their Invasive Pneumococcal infection.
The serotypes of S. pneumoniae in the HIV positive cases included 3, 7F, 10F, 19A
(n=2), 19F and 31. The estimated incidence of IPD in our HIV cohort was 85.7 per
100,000, (based on an overall HIV cohort size of 3500) which is significantly
higher when compared to the general population in London (local epidemiological
data reported the incidence rate for IPD at 7.5 per 100,000 in London). Given the
higher burden of Invasive Pneumococcal Disease in this cohort, low levels of
vaccination, and the predominance of vaccine sensitive strains in our cases,
vaccination and strategies to improve vaccine uptake is a priority in this at
risk group.
PMID- 25128804
TI - Characteristics of test anxiety among medical students and congruence of
strategies to address it.
AB - INTRODUCTION: Medical students may experience test anxiety associated with 'high
stakes' exams, such as Step 1 of the United States Medical Licensing Examination.
METHODS: We collected qualitative responses about test anxiety at three points in
time from 93 second-year medical students engaged in studying for and taking Step
1. RESULTS: Causes of test anxiety as reported by students were related to
negative self-talk during preparation for the exam. Effects of anxiety had to do
with emotional well-being, cognitive functioning, and physical well-being.
Strategies included socializing with others and a variety of cognitive and
physical approaches. Comparison of individuals' strategies with causes and
effects showed some congruence, but substantial incongruence between the types of
strategies chosen and the reported causes and effects of test anxiety.
DISCUSSION: Students' adoption of a 'menu' of strategies rather than one or two
carefully selected strategies suggest inefficiencies that might be addressed by
interventions, such as advisor-directed conversations with students and
incorporating student self-assessment and strategies for managing anxiety within
courses on test-taking. Such interventions are in need of further study. An
annotated list of evidence-based strategies would be helpful to students and
educators. Most important, test anxiety should be viewed by medical educators as
a 'real' experience, and students would benefit from educator support.
PMID- 25128805
TI - CD31(+) cell transplantation promotes recovery from peripheral neuropathy.
AB - Recently, we reported that human peripheral blood (PB)-derived CD31(+) cells are
highly angiogenic. In this study, we investigated the beneficial effects of
CD31(+) cells on peripheral neuropathy in mice. CD31(+) cells were collected from
the peripheral blood using magnetic activated cell sorting. CD31(+) cells
exhibited higher levels of expression of angiogenic genes on real-time reverse
transcriptase polymerase chain reaction. Peripheral neuropathy was induced by
crushing the sciatic nerve with a hemostat, and CD31(+) cells were then injected
intramuscularly along the sciatic nerve. CD31(+) cell transplantation restored
motor nerve conduction velocity and voltage amplitude and improved motor
coordination. In addition, CD31(+) cell transplantation significantly improved
blood perfusion and increased intraneural vascularity in the sciatic nerve. Whole
mount fluorescent imaging and dot blot analysis showed that CD31(+) cells in the
nerve possessed high engraftment and anti-apoptotic properties. Additionally,
injected CD31(+) cells displayed neurovascular tropism and are highly
incorporated with vasculature. Angiogenic cytokines were augmented in CD31(+)
injected nerve tissue, suggesting increased neovascularization. Taken together,
these results indicate that CD31(+) cells might be a novel therapeutic strategy
in the treatment of peripheral neuropathy.
PMID- 25128808
TI - Disruptive innovation: value-based health plans.
AB - VALUE AND A COMPLEX HEALTHCARE MARKET: "Worth in usefulness or importance to the
possessor; utility or merit." American Heritage Dictionary "A principle,
standard, or quality considered worthwhile or desirable." American Heritage
Stedman's Medical Dictionary "A fair return or equivalent in goods, services, or
money for something exchanged." Merriam-Webster's Dictionary of Law.
PMID- 25128807
TI - Building public health capacity in Madhya Pradesh through academic partnership.
AB - Engaging in partnerships is a strategic means of achieving objectives common to
each partner. The Post Graduate Diploma in Public Health Management (PGDPHM)
partners in consultation with the government and aims to strengthen the public
health managerial capacity. This case study examines the PGDPHM program conducted
jointly by the Public Health Foundation of India and the Government of Madhya
Pradesh (GoMP) at the State Institute of Health Management and Communication,
Gwalior, which is the apex training and research institute of the state
government for health professionals. This is an example of collaborative
partnership between an academic institution and the Department of Public Health
and Family Welfare, GoMP. PGDPHM is a 1-year, fully residential course with a
strong component of field-based project work, and aims to bridge the gap in
public health managerial capacity of the health system through training of health
professionals. The program is uniquely designed in the context of the National
Rural Health Mission and uses a multidisciplinary approach with a focus on inter
professional education. The curriculum is competency driven and health systems
connected and the pedagogy uses a problem-solving approach with multidisciplinary
faculty from different programs and practice backgrounds that bring rich field
experience to the classroom. This case study presents the successful example of
the interface between academia and the health system and of common goals achieved
through this partnership for building capacity of health professionals in the
state of Madhya Pradesh over the past 3 years.
PMID- 25128806
TI - Tropical influenza and weather variability among children in an urban low-income
population in Bangladesh.
AB - BACKGROUND: Influenza seasonality in the tropics is poorly understood and not as
well documented as in temperate regions. In addition, low-income populations are
considered highly vulnerable to such acute respiratory disease, owing to limited
resources and overcrowding. Nonetheless, little is known about their actual
disease burden for lack of data. We therefore investigated associations between
tropical influenza incidence and weather variability among children under five in
a poor urban area of Dhaka, Bangladesh. DESIGN: Acute respiratory illness data
were obtained from a population-based respiratory and febrile illness
surveillance dataset of Kamalapur, a low-income urban area in southeast Dhaka.
Analyzed data were from January 2005 through December 2008. Nasopharyngeal wash
specimens were collected from every fifth eligible surveillance participant
during clinic visits to identify influenza virus infection with viral culture and
reverse transcriptase-polymerase chain reaction. Time series analysis was
conducted to determine associations between the number of influenza cases per
week and weather factors. Zero-inflated Poisson and generalized linear Poisson
models were used in the analysis for influenza A and B, respectively. RESULTS:
Influenza A had associations with minimum temperature, relative humidity (RH),
sunlight duration, and rainfall, whereas only RH was associated with influenza B.
Although associations of the other weather factors varied between the two
subtypes, RH shared a similar positive association when humidity was
approximately 50-70%. CONCLUSIONS: Our findings of a positive RH association is
consistent with prior studies, and may suggest the viral response in the tropics.
The characteristics of settlement areas, population demographics, and typical
overcrowding of urban poverty may also contribute to different impacts of
rainfall from higher economic population. Further investigations of associations
between tropical influenza and weather variability for urban low-income
populations are required for better understanding.
PMID- 25128809
TI - PAR polarity: from complexity to design principles.
AB - The par-titioning-defective or PAR proteins comprise the core of an essential
cell polarity network that underlies polarization in a wide variety of cell types
and developmental contexts. The output of this network in nearly every case is
the establishment of opposing and complementary membrane domains that define a
cell's polarity axis. Yet, behind this simple pattern is a complex system of
interactions, regulation and dynamic behaviors. How these various parts combine
to generate polarized patterns of protein localization in cells is only beginning
to become clear. This review, part of the Special Issue on Cell Polarity, aims to
highlight several emerging themes and design principles that underlie the process
of cell polarization by components of the PAR network.
PMID- 25128810
TI - The protective effect of hispidin against hydrogen peroxide-induced apoptosis in
H9c2 cardiomyoblast cells through Akt/GSK-3beta and ERK1/2 signaling pathway.
AB - Hispidin, a phenolic compound from Phellinus linteus (a medicinal mushroom), has
been shown to possess strong anti-oxidant, anti-cancer, anti-diabetic, and anti
dementia properties. However, the cardioprotective efficacy of hispidin has not
yet been investigated. In the present study, we investigated the protective
effect of hispidin against oxidative stress-induced apoptosis in H9c2
cardiomyoblast cells and neonatal rat ventricular myocytes. While the treatment
of H9c2 cardiomyoblast cells with hydrogen peroxide caused a loss of cell
viability and an increase in the number of apoptotic cells, hispidin
significantly protected the cells against hydrogen peroxide-induced cell death
without any cytotoxicity as determined by XTT assay, LDH release assay, Hoechst
33342 assay, and Western blotting of apoptosis proteins such as caspase-3, Bax,
and Bcl-2. Our data also shows that hispidin significantly scavenged
intracellular ROS, and markedly enhanced the expression of antioxidant enzymes
such as heme oxygenase-1 and catalase, which was accompanied by the concomitant
activation of Akt/GSK-3beta and ERK1/2 phosphorylation in H9c2 cardiomyoblast
cells. The effects of hispidin on Akt and ERK phosphorylation were abrogated by
LY294002 (a PI3K/Akt inhibitor) and U0126 (an ERK1/2 inhibitor). The effect of
hispidin on GSK-3b activities was also blocked by LY294002. Furthermore,
inhibiting the Akt/GSK-3beta and ERK1/2 pathway by these inhibitors significantly
reversed the hispidin-induced Bax and Bcl-2 expression, apoptosis induction, and
ROS production. These findings indicate that hispidin protects against apoptosis
in H9c2 cardiomyoblast cells exposed to hydrogen peroxide through reducing
intracellular ROS production, regulating apoptosis-related proteins, and the
activation of the Akt/GSK-3beta and ERK1/2 signaling pathways.
PMID- 25128811
TI - Histopathological and in vivo evidence of regucalcin as a protective molecule in
mammary gland carcinogenesis.
AB - Regucalcin (RGN) is a calcium-binding protein, which has been shown to be
underexpressed in cancer cases. This study aimed to determine the association of
RGN expression with clinicopathological parameters of human breast cancer. In
addition, the role of RGN in malignancy of mammary gland using transgenic rats
overexpressing the protein (Tg-RGN) was investigated. Wild-type (Wt) and Tg-RGN
rats were treated with 7,12-dimethylbenz[alpha]anthracene (DMBA). Carcinogen
induced tumors were histologically classified and the Ki67 proliferation index
was estimated. Immunohistochemistry analysis showed that RGN immunoreactivity was
negatively correlated with the histological grade of breast infiltrating ductal
carcinoma suggesting that progression of breast cancer is associated with loss of
RGN. Tg-RGN rats displayed lower incidence of carcinogen-induced mammary gland
tumors, as well as lower incidence of invasive forms. Moreover, higher
proliferation was observed in non-invasive tumors of Wt animals comparatively
with Tg-RGN. Overexpression of RGN was associated with diminished expression of
cell-cycle inhibitors and increased expression of apoptosis inducers. Augmented
activity of apoptosis effector caspase-3 was found in the mammary gland of Tg
RGN. RGN overexpression protected from carcinogen-induced mammary gland tumor
development and was linked with reduced proliferation and increased apoptosis.
These findings indicated the protective role of RGN in the carcinogenesis of
mammary gland.
PMID- 25128812
TI - Src inhibition potentiates antitumoral effect of paclitaxel by blocking tumor
induced angiogenesis.
AB - The protein kinase Src is frequently over-activated in advanced cancers where it
modulates the signaling transduction cascade of several growth factors. The
feasibility of combination treatment of Src inhibitors with chemotherapy is
currently under investigation. We evaluated the anti-tumoral effect of paclitaxel
(PTX) in combination with S13, a tyrosine kinase inhibitor with a prevalent
specificity for Src, in a hormone-insensible prostate cancer (PCa) cell model. In
vivo, combination treatment with PTX and S13 reduced dramatically PCa tumor
growth with a relevant difference in the density of new blood vessels with
respect to control and single treatments. This reduction was determined by a
concomitant impairment of endothelial cell migration and of VEGF release by
cancer cells. In fact, S13, when used alone, was sufficient to reduce tubule
formation in vivo, and to inhibit VEGFR2 activation and FAK expression in
endothelial cells. In addition, the combination treatment determined a
significant reduction in ROS production and HIF-1 stabilization in PCa cells
respect to single treatments with S13 or PTX. In conclusion, Src-inhibition could
be an effective therapeutic strategy aimed at supporting the anti-angiogenic
action of PTX in aggressive PCa.
PMID- 25128813
TI - Mammalian aPKC/Par polarity complex mediated regulation of epithelial division
orientation and cell fate.
AB - Oriented cell division is a key regulator of tissue architecture and crucial for
morphogenesis and homeostasis. Balanced regulation of proliferation and
differentiation is an essential property of tissues not only to drive
morphogenesis but also to maintain and restore homeostasis. In many tissues
orientation of cell division is coupled to the regulation of differentiation
producing daughters with similar (symmetric cell division, SCD) or differential
fate (asymmetric cell division, ACD). This allows the organism to generate cell
lineage diversity from a small pool of stem and progenitor cells. Division
orientation and/or the ratio of ACD/SCD need to be tightly controlled. Loss of
orientation or an altered ratio can promote overgrowth, alter tissue architecture
and induce aberrant differentiation, and have been linked to morphogenetic
diseases, cancer and aging. A key requirement for oriented division is the
presence of a polarity axis, which can be established through cell intrinsic
and/or extrinsic signals. Polarity proteins translate such internal and external
cues to drive polarization. In this review we will focus on the role of the
polarity complex aPKC/Par3/Par6 in the regulation of division orientation and
cell fate in different mammalian epithelia. We will compare the conserved
function of this complex in mitotic spindle orientation and distribution of cell
fate determinants and highlight common and differential mechanisms in which this
complex is used by tissues to adapt division orientation and cell fate to the
specific properties of the epithelium.
PMID- 25128815
TI - Hierarchical organization of fetal and adult hematopoietic stem cells.
AB - Mammalian hematopoiesis is a hierarchically organized process in which all types
of mature blood cells are continuously generated from more primitive cells that
lack any morphological evidence of differentiation. However, it is now accepted
that this morphologically homogeneous precursor population consists of multiple
distinct subsets of cells. The most primitive of these are defined by their
ability to produce similarly undifferentiated progeny through many cell
divisions, in addition to generating cells with activated differentiation
programs. The term hematopoietic stem cell (HSC) is now conventionally restricted
to cells with this long-term self-sustaining ability. Nevertheless, clonal
tracking studies have revealed significant heterogeneity in the behavior of such
stringently defined HSCs. Moreover, superimposed on the heterogeneous behavior
that can be elicited from the HSCs present at any given time during development
are additional differences that distinguish HSCs at different times both before
and after birth. The latter include changes in the representation of HSCs that
display specific differentiation programs, as well as changes in their turnover
and self-renewal control. Here, we summarize recent studies characterizing these
developmental changes, some of the mechanisms that control them, and their
potential relevance to understanding age-associated differences in leukemia as
well as normal hematopoiesis.
PMID- 25128816
TI - Insight in the multilevel regulation of NER.
AB - Nucleotide excision repair (NER) is a key component of the DNA damage response
(DDR) and it is essential to safeguard genome integrity against genotoxic
insults. The regulation of NER is primarily mediated by protein post
translational modifications (PTMs). The NER machinery removes a wide spectrum of
DNA helix distorting lesions, including those induced by solar radiation, through
two sub-pathways: global genome nucleotide excision repair (GG-NER) and
transcription coupled nucleotide excision repair (TC-NER). Severe clinical
consequences associated with inherited NER defects, including premature ageing,
neurodegeneration and extreme cancer-susceptibility, underscore the biological
relevance of NER. In the last two decades most of the core NER machinery has been
elaborately described, shifting attention to molecular mechanisms that either
facilitate NER in the context of chromatin or promote the timely and accurate
interplay between NER factors and various post-translational modifications. In
this review, we summarize and discuss the latest findings in NER. In particular,
we focus on emerging factors and novel molecular mechanisms by which NER is
regulated.
PMID- 25128814
TI - Raf/MEK/ERK can regulate cellular levels of LC3B and SQSTM1/p62 at expression
levels.
AB - While cellular LC3B and SQSTM1 levels serve as key autophagy markers, their
regulation by different signaling pathways requires better understanding. Here,
we report the mechanisms by which the Raf/MEK/ERK pathway regulates cellular LC3B
and SQSTM1 levels. In different cell types, DeltaRaf-1:ER- or B-Raf(V600E)
mediated MEK/ERK activation increased LC3B-I, LC3B-II, and SQSTM1/p62 levels,
which was accompanied by increased BiP/GRP78 expression. Use of the autophagy
inhibitors chloroquine and bafilomycin A1, or RNA interference of ATG7, suggested
that these increases in LC3B and SQSTM1 levels were in part attributed to altered
autophagic flux. However, intriguingly, these increases were also attributed to
their increased expression. Upon Raf/MEK/ERK activation, mRNA levels of LC3B and
SQSTM1 were also increased, and subsequent luciferase reporter analyses suggested
that SQSTM1 upregulation was mediated at transcription level. Under this
condition, transcription of BiP/GRP78 was also increased, which was necessary for
Raf/MEK/ERK to regulate LC3B at the protein, but not mRNA, level. This suggests
that BiP has a role in regulating autophagy machinery when Raf/MEK/ERK is
activated. In conclusion, these results suggest that, under a Raf/MEK/ERK
activated condition, the steady-state cellular levels of LC3B and SQSTM1 can also
be determined by their altered expression wherein BiP is utilized as an effector
of the signaling.
PMID- 25128817
TI - The Cdk5 activator P39 specifically links muskelin to myosin II and regulates
stress fiber formation and actin organization in lens.
AB - Cyclin dependent kinase 5 (Cdk5), a proline-directed serine/threonine kinase,
requires p39 for its enzymatic activity, and is implicated in cytoskeletal
organization and contraction in numerous cell types. The C-terminus of p39 binds
muskelin, a multi-domain scaffolding protein known to affect cytoskeletal
organization, but the mechanisms by which muskelin affects cytoskeletal
organization remain unclear. The present study sought to determine whether p39
might serve as an adaptor protein that links muskelin to stress fibers and to
investigate the possible biological relevance of such an interaction. Double
immunoprecipitation showed that muskelin, p39, and myosin II are components of a
single intracellular complex, and suppressing p39 abrogated the interaction
between muskelin and the myosin subunits, demonstrating that p39 is required to
link muskelin to myosin II. Muskelin is colocalized with myosin regulatory light
chain (MRLC) and on stress fibers. The suppression of muskelin reduced Rho-GTP,
MRLC phosphorylation, disrupted stress fiber organization, and promoted cell
migration, all of which closely mimic the effect of Cdk5 inhibition. Moreover,
suppressing muskelin and inhibiting Cdk5 together have no additional effect,
indicating that muskelin plays an important role in Cdk5-dependent signaling. p39
is necessary and sufficient for Cdk5-dependent regulation of MRLC
phosphorylation, as suppression of p39, but not p35, reduces MRLC
phosphorylation. Together, these results demonstrate that p39 specifically links
muskelin to myosin II and consequently, to stress fibers and reveal a novel role
for muskelin in regulating myosin phosphorylation and cytoskeletal organization.
PMID- 25128818
TI - Dose-dependent clearance kinetics of intratracheally administered titanium
dioxide nanoparticles in rat lung.
AB - AEROSIL((r)) P25 titanium dioxide (TiO2) nanoparticles dispersed in 0.2% disodium
phosphate solution were intratracheally administered to male F344 rats at doses
of 0 (control), 0.375, 0.75, 1.5, 3.0, and 6.0 mg/kg. The rats were sacrificed
under anesthesia at 1 day, 3 days, 7 days, 4 weeks, 13 weeks, and 26 weeks after
administration. Ti levels in various pulmonary and extrapulmonary organs were
determined using sensitive inductively coupled plasma sector field mass
spectrometry. One day after administration, the lungs contained 62-83% of TiO2
administered dose. Twenty-six weeks after administration, the lungs retained 6.6
8.9% of the TiO2 administered at the 0.375, 0.75, and 1.5 mg/kg doses, and 13%
and 31% of the TiO2 administered at the 3.0 and 6.0 mg/kg doses, respectively.
The pulmonary clearance rate constants from compartment 1, k1, were estimated
using a 2-compartment model and were found to be higher for the 0.375 and 0.75
mg/kg doses of TiO2 (0.030/day for both) than for TiO2 doses of 1.5-6.0 mg/kg
(0.014-0.022/day). The translocation rate constants from compartment 1 to 2, k12,
were estimated to be 0.015 and 0.018/day for the 0.375 and 0.75 mg/kg doses, and
0.0025-0.0092/day for doses of 1.5-6.0mg/kg. The pulmonary clearance rate
constants from compartment 2, k2, were estimated to be 0.0086 and 0.0093/day for
doses of 0.375 and 0.75 mg/kg, and 0-0.00082/day for 1.5-6.0 mg/kg doses.
Translocation of TiO2 from the lungs to the thoracic lymph nodes increased in a
time- and dose-dependent manner, accounting for 0.10-3.4% of the administered
dose at 26 weeks. The measured thoracic lymph node burdens were a much better fit
to the thoracic lymph node burdens estimated assuming translocation from
compartment 1 to the thoracic lymph nodes, rather than those estimated assuming
translocation from compartment 2 to the thoracic lymph nodes. The translocation
rate constants from the lungs to the thoracic lymph nodes, kLung->Lym, were
0.000037-0.00081/day, and these also increased with increasing doses of TiO2.
Although a small amount of TiO2 had translocated to the liver by 3 days after the
administration (0.0023-0.012% of the highest dose administered, 6.0 mg/kg),
translocation to the other extrapulmonary organs was not detected.
PMID- 25128819
TI - Tactual perception of liquid material properties.
AB - In this paper, studies into the tactual perception of two liquid material
properties, viscosity and wetness, are reviewed. These properties are very
relevant in the context of interaction with liquids, both real, such as cosmetics
or food products, and simulated, as in virtual reality or teleoperation. Both
properties have been the subject of psychophysical characterisation in terms of
magnitude estimation experiments and discrimination experiments, which are
discussed. For viscosity, both oral and manual perception is discussed, as well
as the perception of the viscosity of a mechanical system. For wetness, the
relevant cues are identified and factors affecting perception are discussed.
Finally, some conclusions are drawn pertaining to both properties.
PMID- 25128820
TI - Safety pharmacology in 2014: new focus on non-cardiac methods and models.
AB - "What do you know about Safety Pharmacology?" This is the question that was asked
in 2000 with the inception of the Safety Pharmacology Society (SPS). There is now
a widespread awareness of the role of safety pharmacology in drug discovery and
increasing awareness among the wider community of methods and models used in the
assessment of the core battery required set of safety studies. However, safety
pharmacology does not stop with core battery studies. New methods are intensively
sought in order to achieve a swifter and more reliable assessment of adverse
effect liability. The dynamics of the discipline and method expansion are
reflected in the content of this issue of the Journal of Pharmacological and
Toxicological Methods (JPTM). We are into the second decade of publishing on
safety pharmacology methods and models, reflected by the annual themed issue in
JPTM, and on willingness of investigators to embrace new technologies and
methodologies. This years' themed issue is derived from the annual Safety
Pharmacology Society (SPS) meeting, held in Rotterdam, The Netherlands, in 2013.
PMID- 25128821
TI - Redesigning acute care for cognitively impaired older adults: Optimizing health
care services.
AB - PURPOSE OF THE STUDY: Cognitive impairment (CI) is one of several factors known
to influence hospitalization, hospital length of stay, and rehospitalization
among older adults. Redesigning care delivery systems sensitive to the influence
of CI may reduce acute care utilization while improving care quality. To develop
a foundation of fundamental needs for health care redesign, we conducted focus
groups with inpatient and outpatient providers to identify barriers,
facilitators, and suggestions for improvements in care delivery for patients with
CI. DESIGN AND METHODS: Focus group sessions were conducted with providers to
identify their approach to caring for cognitively impaired hospitalized adults;
obstacles and facilitators to providing this care; and suggestions for improving
the care process. Using a thematic analysis, two reviewers analyzed these
transcripts to develop codes and themes. RESULTS: Seven themes emerged from the
focus group transcripts. These were: (1) reflections on serving the cognitively
impaired population; (2) descriptions of perceived barriers to care; (3)
strategies that improve or facilitate caring for hospitalized older adults; (4)
the importance of fostering a hospital friendly to the needs of older adults; (5)
the need for educating staff, patients, and caregivers; (6) the central role of
good communication; and (7) steps needed to provide more effective care.
IMPLICATIONS: Providing effective acute care services to older adults with CI is
an important challenge in health care reform. An understanding derived from the
perspective of multiple professional disciplines is an important first step.
Future research will build on this preliminary study in developing new acute care
models for patients with CI.
PMID- 25128823
TI - Mutational analysis of critical residues of FAD-independent catabolic
acetolactate synthase from Enterococcus faecalis V583.
AB - Catabolic acetolactate synthase (cALS) from Enterococcus faecalis is a FAD
independent enzyme, which catalyzes the condensation of two molecules of pyruvate
to produce acetolactate. Mutational and kinetic analyses of variants suggested
the importance of H111, Q112, and Q411 residues for catalysis in cALS. The wild
type and variants were expressed as equally soluble proteins and co-migrated to a
size of 60 kDa on SDS-PAGE. Importantly, H111 in cALS, which is widely present as
phenylalanine in many other ThDP-dependent enzymes, plays a crucial role in
substrate binding. Interestingly, the H111 variants, H111R and H111F,
demonstrated altered specific activity of H111 variants with 17- and 26-fold
increases in Km, respectively, compared to wild-type cALS. Furthermore, Q112
variants, Q112E, Q112N, and Q112V, exhibited significantly lower specific
activity with 70-, 15-, and 10-fold higher Ks for ThDP, respectively. In the case
of Q411, the variant Q411E showed a 10-fold rise in Km and a 20-fold increase in
Ks for ThDP. Further, the molecular docking results indicated that the binding
mode of ThDP was slightly affected in the variants of cALS. Based on these
results, we suggest that H111 plays a role in substrate binding, and further
suggest that Q112 and Q411 might be involved in ThDP binding of cALS.
PMID- 25128822
TI - Differentiating the Influences of Aging and Adiposity on Brain Weights, Levels of
Serum and Brain Cytokines, Gastrointestinal Hormones, and Amyloid Precursor
Protein.
AB - Aging and obesity exert important effects on disease. Differentiating these
effects is difficult, however, because weight gain often accompanies aging. Here,
we used a nested design of aged, calorically restricted, and refed rats to
measure changes in brain and blood levels of cytokines and gastrointestinal
hormones, brain amyloid precursor protein levels, and brain and body weights. By
comparing groups and using path analysis, we found divergent influences of
chronological aging versus body weight, our main findings being (i) changes in
whole brain weight and serum macrophage colony-stimulating factor levels
correlated better with body weight than with chronological aging, (ii) a decrease
in brain cytokines and brain plasminogen activator inhibitor levels correlated
better with chronological aging than with body weight, (iii) serum erythropoietin
levels were influenced by both body weight and aging, (iv) serum plasminogen
activator inhibitor, serum cytokines, and brain tumor necrosis factor were not
influenced by aging or body weight, and (v) brain amyloid precursor protein more
closely related to body weight and serum levels of gastrointestinal hormones than
to brain weight, chronological aging, or cytokines. These findings show that
although aging and body weight interact, their influences are distinct not only
among various cytokines and hormones but also between the central nervous system
and the peripheral tissue compartments.
PMID- 25128824
TI - Synthesis and characterization of water soluble O-carboxymethyl chitosan Schiff
bases and Cu(II) complexes.
AB - In this study, mono-imine was synthesized (3a and 4a) via a condensation reaction
between 2,4-pentadion and aminobenzoic acid (meta or para) in alcohol (1:1). The
second-imine (CS-3a and CS-4a) was obtained as a result of the reaction of the
free oxo groups of mono-imine (3a and 4a) with the amino groups on the chitosan
(CS). Their structures were characterized with FTIR and (13)C CP-MAS. Then, the
water soluble forms of CS-3a and CS-4a were obtained through oxidation of the
hydroxide groups on the chitosan to carboxymethyl groups using monochloracetic
acid ([O-CMCS-3a] . 2H2O and [O-CMCS-4a] . 2H2O). Thus, the solubility problem of
chitosan in an aqueous media was overcome and Cu(II) complexes could be
synthesized more easily. Characterization of the synthesized O-carboxymethyl
chitosan Schiff base derivatives and their metal complexes, [O-CMCS-3a-Cu(OAc)2]
. 2H2O and [O-CMCS-4a-Cu(OAc)2] . 2H2O, was conducted using FTIR, UV-Vis, TG/DTA,
XRD, SEM, elemental analysis, conductivities and magnetic susceptibility
measurements.
PMID- 25128825
TI - Modulation of cytokine expression in human macrophages by endocrine-disrupting
chemical Bisphenol-A.
AB - Exposure to environmental endocrine-disrupting chemical Bisphenol-A (BPA) is
often associated with dysregulated immune homeostasis, but the mechanisms remain
unclear. In the present study, the effects of BPA on the cytokines responses of
human macrophages were investigated. Treatment with BPA increased pro
inflammation cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6
(IL-6) production, but decreased anti-inflammation cytokines interleukin-10 (IL
10) and transforming growth factor-beta (TGF-beta) production in THP1
macrophages, as well as in primary human macrophages. BPA effected cytokines
expression through estrogen receptor alpha/beta (ERalpha/beta)-dependent
mechanism with the evidence of ERalpha/beta antagonist reversed the expression of
cytokines. We also identified that activation of extracellular regulated protein
kinases (ERK)/nuclear factor kappaB (NF-kappaB) signal cascade marked the effects
of BPA on cytokines expression. Our results indicated that BPA effected
inflammatory responses of macrophages via modulating of cytokines expression, and
provided a new insight into the link between exposure to BPA and human health.
PMID- 25128826
TI - Identification of a telomeric DNA-binding protein in Eimeria tenella.
AB - Coccidiosis is considered to be a major problem for the poultry industry, and
coccidiosis control is yet urgent. Due to the roles in telomere length regulation
and end protection, telomere-binding proteins have been considered as a good
target for drug design. In this work, a putative Gbp1p that is similar to
telomeric DNA-binding protein Gbp (G-strand binding protein) of Cryptosporidium
parvum, was searched in the database of Eimeria tenella. Sequence analysis
indicated E.tenella Gbp1p (EtGbp1p) has significant sequence similarity to other
eukaryotic Gbps in their RNA recognition motif (RRM) domains. Electrophoretic
mobility shift assays (EMSAs) demonstrated recombinant EtGbp1p bound G-rich
telomeric DNA, but not C-rich or double-stranded telomeric DNA sequences.
Competition and antibody supershift assays confirmed the interaction of DNA
protein complex. Chromatin immunoprecipitation assays confirmed that EtGbp1p
interacted with telomeric DNA in vivo. Collectively, these evidences suggest that
EtGbp1p represents a G-rich single-stranded telomeric DNA-binding protein in
E.tenella.
PMID- 25128827
TI - PGE2-induced colon cancer growth is mediated by mTORC1.
AB - The inflammatory prostaglandin E2 (PGE2) cytokine plays a key role in the
development of colon cancer. Several studies have shown that PGE2 directly
induces the growth of colon cancer cells and furthermore promotes tumor
angiogenesis by increasing the production of the vascular endothelial growth
factor (VEGF). The signaling intermediaries implicated in these processes have
however not been fully characterized. In this report, we show that the
mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in
PGE2-induced colon cancer cell responses. Indeed, stimulation of LS174T cells
with PGE2 increased mTORC1 activity as observed by the augmentation of S6
ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE2 EP4
receptor was responsible for transducing the signal to mTORC1. Moreover, PGE2
increased colon cancer cell proliferation as well as the growth of colon cancer
cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP
competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition
of mTORC1 by downregulation of its component raptor using RNA interference
blocked PGE2-induced LS174T cell growth. Finally, stimulation of LS174T cells
with PGE2 increased VEGF production which was also prevented by mTORC1
inhibition. Taken together, these results show that mTORC1 is an important
signaling intermediary in PGE2 mediated colon cancer cell growth and VEGF
production. They further support a role for mTORC1 in inflammation induced tumor
growth.
PMID- 25128829
TI - Structure based modification of Bluetongue virus helicase protein VP6 to produce
a viable VP6-truncated BTV.
AB - Bluetongue virus core protein VP6 is an ATP hydrolysis dependent RNA helicase.
However, despite much study, the precise role of VP6 within the viral capsid and
its structure remain unclear. To investigate the requirement of VP6 in BTV
replication, we initiated a structural and biological study. Multinuclear nuclear
magnetic resonance spectra were assigned on his-tagged full-length VP6 (329 amino
acid residues) as well as several truncated VP6 variants. The analysis revealed a
large structured domain with two large loop regions that exhibit significant
conformational exchange. One of the loops (amino acid position 34-130) could be
removed without affecting the overall fold of the protein. Moreover, using a BTV
reverse genetics system, it was possible to demonstrate that the VP6-truncated
BTV was viable in BHK cells in the absence of any helper VP6 protein, suggesting
that a large portion of this loop region is not absolutely required for BTV
replication.
PMID- 25128830
TI - Identification of borrelidin binding site on threonyl-tRNA synthetase.
AB - Borrelidin exhibits a wide spectrum of biological activities and has been
considered as a non-competitive inhibitor of threonyl-tRNA synthetase (ThrRS).
However, the detailed mechanisms of borrelidin against ThrRS, especially
borrelidin binding site on ThrRS, are still unclear, which limits the development
of novel borrelidin derivatives and rational design of structure-based ThrRS
inhibitors. In this study, the binding site of borrelidin on Escherichia coli
ThrRS was predicted by molecular docking. To validate our speculations, the ThrRS
mutants of E. coli (P424K, E458Delta, and G459Delta) were constructed and their
sensitivity to borrelidin was compared to that of the wild-type ThrRS by enzyme
kinetics and stopped-flow fluorescence analysis. The docking results showed that
borrelidin binds the pocket outside but adjacent to the active site of ThrRS,
consisting of residue Y313, R363, R375, P424, E458, G459, and K465. Site-directed
mutagenesis results showed that sensitivities of P424K, E458Delta, and G459Delta
ThrRSs to borrelidin were reduced markedly. All the results showed that residue
Y313, P424, E458, and G459 play vital roles in the binding of borrelidin to
ThrRS. It indicated that borrelidin may induce the cleft closure, which blocks
the release of Thr-AMP and PPi, to inhibit activity of ThrRS rather than inhibit
the binding of ATP and threonine. This study provides new insight into inhibitory
mechanisms of borrelidin against ThrRS.
PMID- 25128831
TI - Experimental in vitro infection of rat osteoblasts with measles virus stimulates
osteogenic differentiation.
AB - In this work we characterized the infection of a primary culture of rat
osteoblastic lineage cells (OBCs) with measles virus (MeV) and the effect of
infection on cell differentiation and maturation. Infection of OBCs with MeV led
to high titers of infectivity released early after infection. Also, analysis of
mRNAs corresponding to osteogenic differentiation markers like alkaline
phosphatase (ALP), bone sialo-protein (BSP) and bone morphogenetic proteins
(BMPs) 1-4-5-7 in OBCs revealed higher values (2-75-fold of increment) for
infected cells in comparison with uninfected controls. Differentiation of OBCs in
osteogenic medium prior to infection influenced the level of stimulation induced
by MeV. Furthermore, treatment of OBCs with Ly294002, a PI3K/AKT inhibitor,
increased viral titers, whereas treatment with 10MUM or 100MUM ATPgammaS
diminished MeV multiplication. In addition, increments of osteogenic
differentiation markers induced by MeV infection were not modified either by
treatment with Ly294002 or ATPgammaS. These data provide the first evidence
demonstrating that MeV can infect osteoblasts in vitro leading to osteoblastic
differentiation, a key feature in bone pathogenic processes like otosclerosis.
PMID- 25128832
TI - Attitudes and beliefs of health risks associated with sodium intake in diabetes.
AB - BACKGROUND: Despite good evidence that reducing sodium intake can reduce blood
pressure (BP), salt intake in people with type 1 diabetes (T1DM) or type 2
diabetes (T2DM) remains high. The purpose of this study was to describe the
knowledge and beliefs of health risks associated with a high salt diet in adults
with diabetes. METHODS: Men and women with T1DM (n = 27; age 38 +/- 16 years) or
T2DM (n = 124; age 60 +/- 11 years) were recruited. RESULTS: Nine (6.0%)
respondents knew the correct maximum daily recommended upper limit for salt
intake. Thirty-six (23.9%) participants were not concerned with the amount of
salt in their diet. Most participants knew that a diet high in salt was related
to high BP (88.1%) and stroke (78.1%) and that foods such as pizza (80.8%) and
bacon (84.8%) were high in salt. Fewer than 30% of people knew that foods such as
white bread, cheese and breakfast cereals are high in salt (white bread 28.5%,
cheese 29.1%, breakfast cereals 19.9%) and 51.0% correctly ranked three different
nutrition information panels based on the sodium content. Label reading and
purchase of low salt products was used by 60-80% of the group. Estimated average
24 hour urinary sodium excretion was 169 +/- 32 mmol/24 h in men and 115 +/- 27
mmol/24 h in women. CONCLUSION: Label reading and purchase of low salt products
was used by the majority of the group but their salt excretion was still high.
Men who used label reading had a lower salt intake. Other strategies to promote a
lower sodium intake such as reducing sodium in staple foods such as bread need
investigation.
PMID- 25128833
TI - "She got more than me". Social comparison and the social context of eating.
AB - Eating is a social activity for most people. Other people influence what and how
much an individual chooses and eats. Such social influence on eating has long
been recognized and studied, but we contend here that one important social
influence factor, social comparison, has been largely overlooked by researchers.
We review the literature on comparing oneself to others on eating and weight
related dimensions, which appears to have an effect not only on eating per se,
but also on self-image, body dissatisfaction, and emotions. Social comparison
processes may well underlie many of the social influence findings discussed in
this special issue.
PMID- 25128828
TI - DNA methylation and microRNA biomarkers for noninvasive detection of gastric and
colorectal cancer.
AB - Cancer initiation and progression is controlled by both genetic and epigenetic
events. Epigenetics refers to the study of mechanisms that alter gene expression
without permanently altering the DNA sequence. Epigenetic alterations are
reversible and heritable, and include changes in histone modifications, DNA
methylation, and non-coding RNA-mediated gene silencing. Disruption of epigenetic
processes can lead to altered gene function and malignant cellular
transformation. Aberrant epigenetic modifications occur at the earliest stages of
neoplastic transformation and are now believed to be essential players in cancer
initiation and progression. Recent advances in epigenetics have not only offered
a deeper understanding of the underlying mechanism(s) of carcinogenesis, but have
also allowed identification of clinically relevant putative biomarkers for the
early detection, disease monitoring, prognosis and risk assessment of cancer
patients. At this moment, DNA methylation and non-coding RNA including with
microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) represent the largest body
of available literature on epigenetic biomarkers with the highest potential for
cancer diagnosis. Following identification of cell-free nucleic acids in
systematic circulation, increasing evidence has demonstrated the potential of
cell-free epigenetic biomarkers in the blood or other body fluids for cancer
detection. In this article, we summarize the current state of knowledge on
epigenetic biomarkers - primarily DNA methylation and non-coding RNAs - as
potential substrates for cancer detection in gastric and colorectal cancer, the
two most frequent cancers within the gastrointestinal tract. We also discuss the
obstacles that have limited the routine use of epigenetic biomarkers in the
clinical settings and provide our perspective on approaches that might help
overcome these hurdles, so that these biomarkers can be readily developed for
clinical management of cancer patients.
PMID- 25128834
TI - Food references and marketing in popular magazines for children and adolescents
in New Zealand: a content analysis.
AB - Food marketing is recognized as an important factor influencing children's food
preferences and consumption. The purpose of this study was to examine the nature
and extent of unhealthy food marketing and non-branded food references in
magazines targeted at and popular among children and adolescents 10-17 years old
in New Zealand. A content analysis was conducted of all food references (branded
and non-branded) found in the five magazines with the highest readership among 10
17 year olds, and the three magazines (of which two were already included among
the five most popular magazines) targeted to 10-17 year olds. For each of the six
magazines, one issue per month (n = 72 issues in total) over a one-year period
(December 2012-January 2014) was included. All foods referenced were classified
into healthy/unhealthy according to the food-based Ministry of Health
classification system. Branded food references (30% of total) were more frequent
for unhealthy (43%) compared to healthy (25%) foods. Magazines specifically
targeted to children and adolescents contained a significantly higher proportion
of unhealthy branded food references (n = 51/71, 72%) compared to the most
popular magazines among children and adolescents (n = 133/317, 42%), of which
most were targeted to women. 'Snack items' such as chocolates and ice creams were
marketed most frequently (n = 104; 36%), while 'vegetables and fruits' were
marketed the least frequently (n = 9; 3%). Direct advertisements accounted for
27% of branded food references and 25% of those featured health or nutrition
claims. Both branded and non-branded food references were common within magazines
targeted at and popular among children and adolescents, and skewed toward
unhealthy foods. This raises concerns about the effectiveness of self-regulation
in marketing and emphasizes that government regulations are needed in order to
curb children's current potential high exposures to unhealthy food marketing. In
addition, magazine editors could take socially responsible editorial positions in
regard to healthy eating.
PMID- 25128835
TI - The effect of non-caloric sweeteners on cognition, choice, and post-consumption
satisfaction.
AB - Consumers often turn to non-caloric sweeteners (NCS) as a means of promoting a
healthy body weight. However, several studies have now linked their long-term use
to increased weight gain, raising the question of whether these products produce
unintended psychological, physiological, or behavioral changes that have
implications for weight management goals. In the following, we present the
results of three experiments bearing on this issue, testing whether NCS
consumption influences how individuals think about and respond to food.
Participants in each of our three experiments were randomly assigned to consume a
sugar-sweetened beverage, an unsweetened beverage, or a beverage sweetened with
NCS. We then measured their cognition (Experiment 1), product choice (Experiment
2), and subjective responses to a sugar-sweetened food (Experiment 3). Results
revealed that consuming NCS-sweetened beverages influences psychological
processes in ways that - over time - may increase calorie intake.
PMID- 25128836
TI - Transcranial direct current stimulation modulates ERP-indexed inhibitory control
and reduces food consumption.
AB - Food craving can be defined as the "urge to eat a specific food". Previous
findings suggest impairment of inhibitory control, specifically a regulatory
deficit in the lateral prefrontal circuitry that is associated with a compulsion
for food. As demonstrated by three previous studies, bilateral transcranial
direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC)
(anode right/cathode left) reduces food craving and caloric intake. We designed
the present study to evaluate the neural mechanisms that underlie these effects.
We replicated the design of one of these previous studies but included
electroencephalographic assessments to register evoked potentials in a Go/No-go
task that contained pictures of food and furniture (a control visual stimulus).
We collected data from nine women (mean age = 23.4 +/- 2 years) in a crossover
experiment. We observed that active DLPFC tDCS (anode right/cathode left),
compared with sham stimulation, reduced the frontal N2 component and enhanced the
P3a component of responses to No-go stimuli, regardless of the stimulus condition
(food or furniture). Active tDCS was also associated with a reduction in caloric
intake. We discuss our findings in the context of cortico-subcortical processing
of craving and tDCS effects on inhibitory control neural circuitry.
PMID- 25128837
TI - Shoppers' perceived embeddedness and its impact on purchasing behavior at an
organic farmers' market.
AB - This study explores the concept of perceived embeddedness (PE) and its impact on
purchasing behavior at an organic farmers' market. Based on a review of the prior
literature, the study refines the conceptualization and measurement of PE as a
second-order factor construct reflected in its three dimensions: perceived social
embeddedness, perceived spatial embeddedness, and perceived natural embeddedness.
The study also suggests that organic farmers' market shoppers' PE is positively
related to the two measures of purchasing behavior: expenditure per visit and
repurchase intention. In a sample of 492 organic farmers' market shoppers in
Beijing municipality, China, the study find support for the second-order factor
structure of PE and the theorized relationship between the shoppers' PE and their
purchasing behavior. The study also discusses theoretical and managerial
implications of the findings.
PMID- 25128838
TI - Minor association of kinase insert domain-containing receptor gene polymorphism
(rs2071559) with myocardial infarction in Caucasians with type 2 diabetes
mellitus: case-control cross-sectional study.
AB - OBJECTIVE: Vascular endothelial growth factor A (VEGF) and its receptor KDR play
central roles in angiogenesis and vascular repair, which occur in diabetic
vascular complications, such as MI. The aim of our study was to investigate if
polymorphisms rs2071559 and rs2305948 in the kinase insert domain-containing
receptor (KDR) gene are associated with myocardial infarction (MI) in Caucasians
with type 2 diabetes (T2DM). DESIGN AND METHODS: The association of KDR -604T>C
(rs2071559) and 1192G>A (rs2305948) polymorphisms was tested in a case-control
cross-sectional study including 171 subjects with T2DM and MI compared to 855
subjects with T2DM without coronary artery disease (CAD). In addition, VEGF serum
levels were analyzed in 98 subjects with type 2 diabetes without CAD. RESULTS: A
significantly higher frequency of the CC genotype of the KDR -604T>C (rs2071559)
polymorphism was found in diabetic patients with MI compared to diabetic patients
without CAD (27.5% vs. 21.1%, p=0.04). On the other hand, the 1192G>A (rs2305948)
polymorphism was not associated with MI in subjects with type 2 diabetes.
Significantly higher VEGF serum levels were found in subjects with the -604CC
genotype compared to those with other (CT+TT) genotypes (73.8 +/- 22.1 ng/l vs.
58.1 +/- 18.5 ng/l; p<0.01). Multiple logistic regression analysis adjusted for
age, arterial hypertension, LDL cholesterol, HDL cholesterol and hsCRP revealed
that carriers of the -604CC genotype (rs2071559) had a 1.6-fold higher risk for
MI (OR=1.6; 95% CI=1.1-2.1; p=0.022). CONCLUSION: The present study demonstrates
that the CC genotype of the KDR -604T>C polymorphism (rs2071559) is a possible
risk factor for MI in Caucasians with T2DM.
PMID- 25128839
TI - Development and validation of a UHPLC diode array detector method for meropenem
quantification in human plasma.
AB - OBJECTIVES: Meropenem is a beta-lactam antibiotic frequently used to treat
serious infections in intensive care unit patients. The main objective was to
develop and validate a sensitive and specific ultra high performance liquid
chromatography method with photodiode array detection for the quantitation of
meropenem in human plasma. The applicability of the method for meropenem
monitoring was also examined. DESIGN AND METHODS: The validation of the method
was performed following the FDA's guidelines for bioanalytical methods. In
parallel, the method was applied for monitoring meropenem in forty plasma samples
from ten critically ill patients treated intravenously at a total dose of 1 g.
Drug levels were measured in each patient at 0 h, 2 h, 4 h and 8 h after
meropenem infusion. RESULTS: With this method, intraday and day-to-day variation
was below 10%; intraday and day-to-day accuracy was between 94% and 114%; the
limit of quantification was 0.5 MUg/mL and recovery was above 70%. The method was
successfully applied to quantitate meropenem concentrations and the results
showed significant pharmacokinetic interindividual variability. Of special
interest is that 50% of treated patients had meropenem plasma levels below the
minimum inhibitory concentration at 8h after the start of infusion, which was
strongly related to creatinine clearance >60 mL/min. CONCLUSIONS: The method
meets the requirements to be applied for meropenem concentration measurements in
pharmacokinetics studies and clinical routine. The results suggest the need for
therapeutic drug monitoring of meropenem in treated critically-ill patients.
PMID- 25128840
TI - Variable effects of the co-administration of a GM-CSF-expressing plasmid on the
immune response to flavivirus DNA vaccines in mice.
AB - As a cytokine adjuvant, granulocyte-macrophage colony-stimulating factor (GM-CSF)
has been demonstrated to play central roles in the enhancement of the immune
response and protection elicited by experimental vaccines. However, in our
previous work, the co-administration of GM-CSF produced untoward effects on the
immune response induced by a Japanese encephalitis virus DNA vaccine candidate.
This study aimed to elucidate the adjuvant roles of GM-CSF in several
Flaviviridae virus DNA vaccine candidates. Our results showed that the effects of
GM-CSF were diverse: co-inoculated GM-CSF caused significant suppression to the
dengue virus type 1 and type 2 prM-E DNA vaccinations and influenced protective
efficiency against virus challenge. In contrast, GM-CSF showed little effect or
an enhancement on the immune response elicited by hepatitis C virus C or E1 DNA
vaccine candidates. Notably, these effects of GM-CSF were highly durable. Our
results suggested that the adjuvant roles of the GM-CSF plasmid were complex and
diverse, ranging from enhancement to suppression, depending on the immunogen of
Flaviviridae virus DNA vaccine candidates. Therefore, the application of GM-CSF
as a vaccine adjuvant or a therapeutic agent should be evaluated carefully.
PMID- 25128841
TI - Murine carcinoma expressing carcinoembryonic antigen-like protein is restricted
by antibody against neem leaf glycoprotein.
AB - We have generated a polyclonal antibody against a novel immunomodulator, neem
leaf glycoprotein (NLGP) that can react to a specific 47 kDa subunit of NLGP.
Generated anti-NLGP antibody (primarily IgG2a) was tested for its anti-tumor
activity in murine carcinoma (EC, CT-26), sarcoma (S180) and melanoma (B16Mel)
tumor models. Surprisingly, tumor growth restriction was only observed in CT-26
carcinoma models, without any alteration in other tumor systems. Comparative
examination of antigenicity between four different tumor models revealed high
expression of CEA-like protein on the surface of CT-26 tumors. Subsequent
examination of the cross-reactivity of anti-NLGP antibody with purified or cell
bound CEA revealed prominent recognition of CEA by anti-NLGP antibody, as
detected by ELISA, Western Blotting and immunohistochemistry. This recognition
seems to be responsible for anti-tumor function of anti-NLGP antibody only on CEA
like protein expressing CT-26 tumor models, as confirmed by ADCC reaction in
CEA(+) tumor systems where dependency to anti-NLGP antibody is equivalent to anti
CEA antibody. Obtained result with enormous therapeutic potential for CEA(+)
tumors may be explained in view of the epitope spreading concept, however,
further investigation is crucial.
PMID- 25128842
TI - And the BBI 2014 award for lead actor in "neuroinflammation and depression" goes
to....
PMID- 25128843
TI - Fractal microstructure characterization of wet microalgal cells disrupted with
ultrasonic cavitation for lipid extraction.
AB - The effects of ultrasonic treatment on fractal microstructures of wet microalgal
cells were investigated for lipid extraction. Fractal dimension of cells with
distorted surfaces increased with power and ultrasonication time. Microalgal
cells shrank owing to dehydration and cytomembranes were reduced to debris, but
cell walls were not fragmented. When ultrasonication power increased from 0 to
500W for 30min, the fractal dimension of cells increased from 1.21 to 1.51, cell
sizes decreased from 2.78 to 1.68MUm and cell wall thickness decreased from 0.08
to 0.05MUm. When ultrasonication time increased from 5 to 30min with a power of
150W, the fractal dimension of cells increased from 1.24 to 1.37, cell sizes
decreased from 2.72 to 2.38MUm and cell wall thickness first increased to a peak
of 0.22MUm and then decreased. Long-chain and unsaturated lipids were degraded
into short-chain and saturated lipids with ultrasonic cavitation.
PMID- 25128844
TI - Recycling of food waste as nutrients in Chlorella vulgaris cultivation.
AB - Heterotrophic cultivation of Chlorella vulgaris was investigated in food waste
hydrolysate. The highest exponential growth rate in terms of biomass of 0.8day(
1) was obtained in a hydrolysate consisting of 17.9gL(-1) glucose, 0.1gL(-1) free
amino nitrogen, 0.3gL(-1) phosphate and 4.8mgL(-1) nitrate, while the growth rate
was reduced in higher concentrated hydrolysates. C. vulgaris utilized the
nutrients recovered from food waste for the formation of biomass and 0.9g biomass
was produced per gram glucose consumed. The microalgal biomass produced in
nutrient sufficient batch cultures consisted of around 400mgg(-1) carbohydrates,
200mgg(-1) proteins and 200mgg(-1) lipids. The conversion of nutrients derived
from food waste and the balanced biomass composition make C. vulgaris a promising
strain for the recycling of food waste in food, feed and fuel productions.
PMID- 25128845
TI - OmGOGAT-disruption in the ericoid mycorrhizal fungus Oidiodendron maius induces
reorganization of the N pathway and reduces tolerance to heavy-metals.
AB - Mycorrhizal fungi are key mediators of soil-to-plant movement of mineral
nutrients, including essential and non-essential metals. In soil conditions that
facilitate mobilization of metal ions, potentially toxic metals can interfere
with nitrogen metabolism in both plants and microorganisms. Less is known about
possible relationships between nitrogen metabolism and responses to heavy metals.
Aim of this study was to investigate this aspect in the ericoid mycorrhizal
fungus Oidiodendron maius strain Zn, a metal tolerant ascomycete. Growth of O.
maius Zn on zinc and cadmium containing media was significantly affected by the
nitrogen source. Screening of a library of O. maius Zn random genetic
transformants for sensitivity to heavy metals (zinc and cadmium) and oxidative
stress (menadione) yielded a mutant strain that carried a partial deletion of the
glutamate synthase (NADH-GOGAT EC 1.4.1.14) gene and its adjacent gene, the APC15
subunit of the anaphase promoting complex. Comparison of WT and OmGOGAT-OmAPC15
mutant strains indicated an impaired N-metabolism and altered stress tolerance,
and assays on the OmAPC15-recomplemented strains ascribed the observed phenotypes
to the deletion in the OmGOGAT gene. OmGOGAT disruption modified the nitrogen
pathway, with a strong reduction of the associated glutamine synthetase (GS, EC
6.3.1.2) activity and an up-regulation of the alternative NADP-glutamate
dehydrogenase (NADP-GDH, EC 1.4.1.4) pathway for glutamate biosynthesis. Unless
they were supplemented with glutamine, O. maius Zn transformants lacking OmGOGAT
were very sensitive to zinc. These results highlight the importance of nitrogen
metabolism not only for nitrogen assimilation and transformation, but also for
stress tolerance. For mycorrhizal fungi, such as O. maius, this may bear
consequences not only to the fungus, but also to the host plant.
PMID- 25128846
TI - Sperm glucose transport and metabolism in diabetic individuals.
AB - Individuals with diabetes mellitus (DM) present marked reduction in sperm quality
and higher DNA damage in spermatozoa, evidencing that this metabolic disorder
impairs male fertility. These effects are related to defective testicular
metabolic pathways and signaling, resulting in altered sperm metabolism.
Spermatozoa metabolize several substrates to ensure energy supplies and any
alteration in this feature compromise sperm quality. For ATP production,
spermatozoa require substrate availability and the involvement of specific hexose
membrane carriers. DM is known to modulate the spermatozoa substrate consumption
and/or production due to altered glycolytic behavior. In fact, glucose uptake and
metabolism is highly deregulated in diabetic individuals. Herein, we present an
overview of the implications of DM in sperm glucose uptake and metabolism. The
understanding of these processes is essential to identify key mechanisms
associated with DM-related male (in)fertility. Moreover, it may contribute to the
development of therapeutics to counteract the dysfunction induced by DM in sperm
metabolism.
PMID- 25128847
TI - Glutamine synthetase plays a role in D-galactose-induced astrocyte aging in vitro
and in vivo.
AB - Astrocytes play multiple roles in physiological and pathological conditions in
brain. However, little is known about the alterations of astrocytes in age
related changes, and few aging models of the astrocytes in vitro have been
established. Therefore, in the present study, we used d-galactose (D-Gal) to
establish astrocyte aging model to explore the alterations of astrocytes in brain
aging. We also used (1)H nuclear magnetic resonance ((1)H NMR) spectra to verify
the metabolic changes in the cerebral cortex of mice injected with D-gal. The
results showed that D-gal (55mM) treatment for 1 week induced senescence
characteristics in cultured cortical astrocytes. Real-time PCR and western blot
analysis showed that the levels of glutamine synthetase (GS) mRNA and protein
were strikingly decreased in the cultured senescent astrocytes, and the senescent
astrocytes showed less resistance to the glutamate-induced gliotoxicity. The
impairments of glutamate-glutamine cycle and astrocytes were also found in the
cerebral cortex of mice treatment with D-gal (100mg/kg) for 6 weeks, and the
level of GS mRNA was also found to be reduced markedly, being consistent with the
result obtained from the senescent astrocytes in vitro. These results indicate
that astrocyte may be the predominant contributor to the pathogenic mechanisms of
D-gal-induced brain aging in mice, and GS might be one of the potential
therapeutic targets of the aged brain induced by D-gal.
PMID- 25128849
TI - Spinal administration of mGluR5 antagonist prevents the onset of bortezomib
induced neuropathic pain in rat.
AB - Peripheral neuropathy is a common adverse effect of bortezomib-based
chemotherapy. In this study we have investigated the role played by subtype 5 of
metabotropic receptors in bortezomib induced peripheral neuropathy. Rats were
administered with bortezomib three times weekly at 0.20 mg/kg for a total of 4
weeks in presence or absence of mGluR5 antagonist MPEP. The animals were
submitted to paw-pressure test and tail sensory nerve conduction measurement more
times during the treatment and follow-up. Bortezomib treatment induced a
progressively increasing hyperalgesia in rat which was accompanied by a
significant reduction in sensory nerve conduction velocity (SNCV). MPEP prevented
the emergence of bortezomib-induced pain and counteracted SNCV reduction when co
administered with bortezomib treatment. Spinal extracellular glutamate levels
increased in rats treated with bortezomib. Bortezomib-induced onset of the
hyperalgesia and SNCV decrease could be prevented by agents that promote the
reuptake of glutamate maintaining spinal glutamate at basal level. Our data
support the manipulation of the glutamatergic system through the mGluR5 receptor
in bortezomib induced peripheral neuropathy. The use of antagonists at the
mGluR5, initiated at the same time as bortezomib-chemotherapy, might reduce the
number of patients who develop painful peripheral chemo-neuropathy.
PMID- 25128850
TI - Altered expression of deltaGABAA receptors in health and disease.
AB - gamma-Aminobutyric acid type A receptors that contain the delta subunit
(deltaGABAA receptors) are expressed in multiple types of neurons throughout the
central nervous system, where they generate a tonic conductance that shapes
neuronal excitability and synaptic plasticity. These receptors regulate a variety
of important behavioral functions, including memory, nociception and anxiety, and
may also modulate neurogenesis. Given their functional significance, deltaGABAA
receptors are considered to be novel therapeutic targets for the treatment of
memory dysfunction, pain, insomnia and mood disorders. These receptors are highly
responsive to sedative-hypnotic drugs, general anesthetics and neuroactive
steroids. A further remarkable feature of deltaGABAA receptors is that their
expression levels are highly dynamic and fluctuate substantially during
development and in response to physiological changes including stress and the
reproductive cycle. Furthermore, the expression of these receptors varies in
pathological conditions such as alcoholism, fragile X syndrome, epilepsy,
depression, schizophrenia, mood disorders and traumatic brain injury. Such
fluctuations in receptor expression have significant consequences for behavior
and may alter responsiveness to therapeutic drugs. This review considers the
alterations in the expression of deltaGABAA receptors associated with various
states of health and disease and the implications of these changes.
PMID- 25128848
TI - Metaplastic effects of subanesthetic ketamine on CA1 hippocampal function.
AB - Ketamine is a non-competitive N-methyl-d-aspartate receptor (NMDAR) antagonist of
interest in neuropsychiatry. In the present studies, we examined the effects of
subanesthetic, low micromolar ketamine on excitatory postsynaptic potentials
(EPSPs), population spikes (PSs) and synaptic plasticity in the CA1 region of rat
hippocampal slices. Ketamine acutely inhibited NMDAR-mediated synaptic responses
with half-maximal effects near 10 MUM. When administered for 15-30 min at 1-10
MUM, ketamine had no effect on baseline dendritic AMPA receptor-mediated EPSPs,
but persistently enhanced somatic EPSPs in the pyramidal cell body layer and
augmented PS firing. Acute low micromolar ketamine also had no effect on the
induction of long-term potentiation (LTP) but blocked long-term depression (LTD).
Following 30 min administration of 1-10 MUM ketamine, however, a slowly
developing and persistent form of LTP inhibition was observed that took two hours
following ketamine washout to become manifest. This LTP inhibition did not result
from prolonged or enhanced NMDAR inhibition during drug washout. Effects of low
ketamine on somatic EPSPs and LTP were not mimicked by a high ketamine
concentration that completely inhibited NMDARs, and both of these effects were
blocked by co-administration of low ketamine with a low concentration of the
competitive NMDAR antagonist, 2-amino-5-phosphonovalerate or inhibitors of nitric
oxide synthase. These results indicate that concentrations of ketamine relevant
to psychotropic and psychotomimetic effects have complex metaplastic effects on
hippocampal function that involve activation of unblocked NMDARs during ketamine
exposure.
PMID- 25128851
TI - Hysteroscopic morcellation: review of the manufacturer and user facility device
experience (MAUDE) database.
AB - STUDY OBJECTIVE: To investigate the number and type of adverse events associated
with hysteroscopic morcellation of intrauterine disease. DESIGN: Systematic
review of Manufacturer and User Device Experience (MAUDE) database from 2005 to
June 2014 (Canadian Task Force classification III). SETTING N/A PATIENTS: Women
undergoing hysteroscopic surgery for removal of intrauterine polyps or myomas
with use of a reciprocating morcellator. INTERVENTIONS: The MAUDE database was
searched for the key words "Hysteroscope," "Hysteroscopic reciprocating
morcellator," "Interlace," "MyoSure," "Smith & Nephew," and "TRUCLEAR," to
identify reported incidences of device malfunction, injury, or death. A total of
119 adverse events were analyzed. Reports were reviewed individually and
categorized by date of occurrence, type of morcellation device, type of
complication, and a brief description. Each company was contacted to provide an
estimate of the number of procedures performed or units sold to date.
MEASUREMENTS AND MAIN RESULTS: From 2005 to June 2014, 119 adverse events were
reported to the MAUDE database. On the basis of severity, adverse events were
categorized as major or minor complications. Major events included
intubation/admission to an intensive care unit (n = 14), bowel damage (n = 12),
hysterectomy (n = 6), and death (n = 2). Minor events included uterine
perforation requiring no other treatment (n = 29), device failure (n = 25),
uncomplicated fluid overload (n = 19), postoperative bleeding controlled using
noninvasive measures (n = 6), and pelvic infection (n = 4). These events were
then categorized according to manufacturer. The number of adverse events reported
to the MAUDE database was divided by the total units sold as a surrogate for the
estimated number of procedures performed. Understanding the limitation of the
numbers used as a numerator and denominator, we concluded that adverse events
complicated hysteroscopic morcellation in <0.1% cases. CONCLUSIONS: The suction
based, mechanical energy, rotating tubular cutting system was developed to
overcome adverse events that occur during traditional resectoscopy. On the basis
of acknowledged limited information from the MAUDE database, it seems that life
threatening complications such as fluid overload, uterine perforation, and
bleeding do occur with hysteroscopic morcellation but less frequently than with
traditional electrocautery.
PMID- 25128852
TI - Development of chitosan oleate ionic micelles loaded with silver sulfadiazine to
be associated with platelet lysate for application in wound healing.
AB - In the treatment of chronic wounds, topical application of anti-infective drugs
such as silver sulfadiazine (AgSD) is of primary importance to avoid infections
and accelerate wound repair. AgSD is used in burns and chronic wounds for its
wide antibacterial spectrum, but presents limitations due to poor solubility and
cytotoxicity. In the present work polymeric micelles obtained by self-assembling
of chitosan ionically modified by interaction with oleic acid were developed as
carriers for AgSD to overcome the drawbacks of the drug. The AgSD loaded micelles
were intended to be associated in wound healing with platelet lysate (PL), a
hemoderivative rich in growth factors. Unloaded micelles demonstrated good
compatibility with both fibroblasts and PL. The relevance of chitosan
concentration and of the ratio between chitosan and oleic acid to the drug
loading and the particle size of nanoparticles was studied. A marked increase (up
to 100 times with respect to saturated solution) of AgSD concentration in micelle
dispersion was obtained. Moreover, the encapsulation reduced the cytotoxic effect
of the drug towards fibroblasts and the drug incompatibility with PDGF-AB
(platelet derived growth factor), chosen as representative of platelet growth
factors.
PMID- 25128853
TI - Study of the Lactobacillus rhamnosus Lcr35(r) properties after compression and
proposition of a model to predict tablet stability.
AB - The beneficial effects of probiotic bacteria on human health are now widely
acknowledged, and this has prompted growing interest in research and development
in the pharmaceutical field. However, to be viable when they reach their target,
the bacteria must be able to survive during the manufacturing process and the
biological pathway. Tablet form best meets the requirements for protecting acid
labile drugs, but the tableting process could be an additional stress for the
bacteria. This study evaluated the initial effect of compression pressure on the
Lcr35(r) strain in a vaginal (Lcr regenerans(r)) and an intestinal (Lcr
restituo(r)) formulation. A stability study was also performed on the tablets and
revealed a beneficial effect of this form. The obtained destruction rates (k)
demonstrated that the bacterial stability was greater in tablets than in powders
(kpowders>ktablets). A new mathematical model was developed combining compression
and temperature parameters to predict the bacterial viability at any pressure and
time. Moreover, the genetic profile of Lcr35(r) (Rep-PCR, microarrays), its
resistance to acidity and its ability to inhibit Candidaalbicans growth, after
compression, were determined to evaluate the target product profile (TPP) in a
Quality by Design (QbD) approach. The Rep-PCR analysis validated the strain
identity and the microarrays demonstrated the genetic stability of Lcr35(r)
strain after compaction. Additionally, ability to inhibit the C. albicans growth
was maintained and the resistance to gastric conditions of Lcr35(r) was even
improved by tableting. As a dosage form, tablets containing probiotic can
guarantee that an adequate amount of bacteria reaches the therapeutic target
(intestinal or vaginal) and that the product remains stable until the time of
consumption.
PMID- 25128854
TI - Development of disulfiram-loaded vaginal rings for the localised treatment of
cervical cancer.
AB - Cervical cancer is the third most prevalent cancer in women and
disproportionately affects those in low resource settings due to limited programs
for screening and prevention. In the developed world treatment for the disease in
the non-metastasised state usually takes the form of surgical intervention and/or
radiotherapy. In the developing world such techniques are less widely available.
This paper describes the development of an intravaginal ring for the localised
delivery of a chemotherapeutic drug to the cervix that has the potential to
reduce the need for surgical intervention and will also provide a novel anti
cancer therapy for women in low resource settings. Disulfiram has demonstrated
antineoplastic action against prostate, breast and lung cancer. Both PEVA and
silicone elastomer were investigated for suitability as materials in the
manufacture of DSF eluting intravaginal rings. DSF inhibited the curing process
of the silicone elastomer, therefore PEVA was chosen as the material to
manufacture the DSF-loaded vaginal rings. The vaginal rings had an excellent
content uniformity while the DSF remained stable throughout the manufacturing
process. Furthermore, the rings provided diffusion controlled release of DSF at
levels well in excess of the IC50 value for the HeLa cervical cancer cell line.
PMID- 25128855
TI - Expression of biologically active TAT-fused recombinant islet transcription
factors.
AB - AIMS: Differentiation of pancreatic endocrine cells depends upon the activation
of genes that are regulated by islet transcription factors (ITFs). Evidence
suggests that ITFs contribute to the development of the pancreas. These studies
are focused on developing a system to deliver individual ITF from different
stages of islet cell development to promote precursors or other cell types to
trans-differentiate into islet-like insulin-positive cells. MAIN METHODS: Protein
transduction domains (PTDs) derived from the HIV-TAT peptide (YGRKKRRQRRR) were
fused with three ITFs, Ngn3, Pdx1, and NeuroD/beta2, to facilitate the uptake of
ITF recombinant proteins into various cell types. The three TAT-fused ITFs, Ngn3,
Pdx1, and NeuroD/beta2 were constructed in a bacterial 6*His affinity tag-TAT
recombinant protein expression system. The recombinant proteins were expressed
using IPTG induction and purified to homogeneity using a nickel affinity column.
KEY FINDINGS: The biological activity of each TAT-fused ITF was demonstrated by
nuclear translocation, induction of target gene promoter activity, and the trans
differentiation of pancreatic acinar cells, AR42J, into insulin-positive cells.
SIGNIFICANCE: This study provides advanced information for developing strategies
using recombinant TAT-fused ITF proteins in place of adenoviral vectors for the
conversion of pancreatic exocrine cells into insulin-positive cells for the
treatment of diabetes.
PMID- 25128856
TI - Epigenetics, the missing link in hypertension.
AB - Epigenetics refers to functional alterations in gene expression or phenotype
without any change of the underlying DNA sequence. It is the study of the
potential of a cell or organism to express different traits through functional
regulation of its gene transcription. Though it is met as a necessary process in
biology, epigenetics may often play a crucial part in the development of specific
pathologic conditions, including cardiovascular diseases and hypertension.
PMID- 25128857
TI - Structure and biological perspectives of Cu(II)-indomethacin complexes.
AB - The copper(II) complexes with the non-steroidal anti-inflammatory drug
indomethacin (Hindo) in the presence of the nitrogen-donor heterocyclic ligands
2,2'-bipyridine (bipy), 1,10-phenanthroline (phen) or 2,2'-bipyridylamine
(bipyam) have been synthesized and characterized. The crystal structures of
[Cu(indo)2(bipy)]?1.5MeOH?0.5H2O and [Cu(indo)2(phen)] ?1.85MeOH?0.15H2O have
been determined by X-ray crystallography. All compounds have been tested for
their antioxidant and free radical scavenging activity as well as for their in
vitro inhibitory activity against soybean lipoxygenase showing significant
activity with the previously reported complex [Cu2(indo)4(H2O)2] being the most
active. The complexes exhibit good binding affinity to human or bovine serum
albumin protein with high binding constant values. UV study of the interaction of
the complexes with calf-thymus (CT) DNA has shown that the complexes can bind to
CT DNA with [Cu(indo)2(bipyam)] showing the highest binding constant to CT DNA
(Kb=1.56(+/-0.19)*10(6)M(-1)). The complexes can bind to CT DNA via intercalation
as concluded by cyclic voltammetry, DNA viscosity measurements and competitive
studies with ethidium bromide (EB) which revealed the ability of the complexes to
displace the DNA-bound EB.
PMID- 25128858
TI - How well do patient activation scores predict depression outcomes one year later?
AB - BACKGROUND: This study examines the relationship between patient activation, a
measure of individuals' knowledge, skill, and confidence for managing their
health, and rates of depression remission and response among patients with
depression. METHODS: Patients from Fairview Health Services in Minnesota with
moderate to severe depression in 2011 and a PHQ-9 score in 2012 were included in
the analysis (n=5253). Patient activation in 2011 and other health and
demographic features were extracted from the electronic health record. We
examined how patient activation predicted depression remission and response rates
and changes in depression severity over one year using regression models. We also
explored how activation predicted healthy behaviors among depressed patients.
RESULTS: Higher baseline patient activation predicted lower depression severity
and higher depression remission and response rates a year later. The most
activated patients had PHQ-9 scores in 2012 two points lower than the lowest
activated patients, and they had twice the odds of remission. Activation also
predicted increase in healthy behaviors. LIMITATIONS: We were unable to examine
the use of mental health services or control for the number of prior depressive
episodes and duration of the current depressive episode in the analysis.
CONCLUSIONS: We found that higher patient activation predicted better depression
outcomes. While we are unable to explore the mechanism of this association, we
observed that more activated patients are also engaged in more healthy behaviors,
suggesting that the mechanism may be behavioral. Support of patient activation
may be an effective approach for providers to reduce patients' depression
severity.
PMID- 25128859
TI - Cyberbullying, psychological distress and self-esteem among youth in Quebec
schools.
AB - BACKGROUND: The advent of new technologies and social media offers a host of
possibilities for teenagers to consolidate social networks. Unfortunately, new
technologies also represent a potential setting for experiences of victimization.
METHODS: The present study explores the prevalence of cyberbullying victimization
in a representative sample of 8 194 teenagers in Quebec and the adverse
associated consequences. RESULTS: Results indicate that 18% of boys and close to
1 out of 4 girls report at least one incident of cyberbullying in the past 12
months. Cyberbullying victimization contributes to the prediction of low
selfesteem and psychological distress over and above other experiences of
bullying in schools or other settings. CONCLUSIONS: Cyberbullying appear as one
important target for the design of prevention and intervention services designed
for youth.
PMID- 25128860
TI - Factors associated with depression and suicide attempts in patients undergoing
rehabilitation for substance abuse.
AB - BACKGROUND: Comorbidity of major depression with substance abuse increases the
risk of committing suicide. The objective of this work was to determine the
psychological and socio-demographic factors associated with depression and
suicide attempts in patients rehabilitating for drug consumption. METHOD: 57
Patients attending a center for drug abuse treatment answered the following
instruments: the Mini-international neuropsychiatric interview, a questionnaire
of general information and background data on consumption of substances,
depression and suicide attempts, and the Spanish adaptation of the Holmes and
Rahe scale for the assessment of life events. Chi-square and logistic regression
tests were used to establish associations between variables. RESULTS: 68.4% of
the Patients had current major depression, of these, 75.4% experienced it before
the onset of substance abuse. Patients attempting suicide before drug use
corresponded to 26%, whilst 28.1% attempted suicide within the last year. Current
depression-related variables were receiving a diagnosis of depression prior to
the consumption of drugs and the first used drugs, which were alcohol or
marijuana. The adverse life event "Familial drug abuse history", was also
significantly related to depression (p=0.02). Variables associated with current
suicide attempts were: receiving a diagnosis of depression prior to the
consumption of drugs (p=0.02), and suicide attempts previous to drug use
(p<0.003). LIMITATION: A limitation of this study was the small size of the
sample. CONCLUSION: Patients with depression who attempted suicide prior to the
use of drugs also experienced these conditions during the rehabilitation process.
Substance use in the family was a risk factor for both, underscoring the need of
actions aimed at preventing addictions in the household environment.
PMID- 25128861
TI - A review of the relationship between proinflammatory cytokines and major
depressive disorder.
AB - BACKGROUND: Determining etiological factors and reviewing advances in diagnostic
modalities sensitive and specific to Major Depressive Disorder (MDD) is of
importance in its evaluation and treatment. The inflammatory hypothesis is one of
the most prevalent topics concerning MDD and may provide insight into the
pathogenesis of depression, development of biomarkers, and ultimately production
of more effective depression therapies. METHOD: We reviewed several studies to
evaluate contemporary concepts concerning proinflammatory cytokines and their
relationship to various depressive disorders, the use of anti-inflammatory
therapies in MDD treatment, and the application of neuroimaging in conjunction
with cytokine profiles from both plasma and CSF as possible diagnostic tools.
RESULTS: Proinflammatory cytokines in both plasma and CSF have been found to
influence the progression and severity of depressive disorders in different
populations. Studies have shown elevated serum levels of IL-1, IL-6, TNF-alpha,
CRP, and MCP-1 in depressed patients, but have presented mixed results with IL-8
serum levels, and with IL-6 and MCP-1 CSF levels. Anti-inflammatory treatment of
MDD may have adjuvant properties with current depression medications. MRI and
NIRS neuroimaging confirm neurological abnormalities in the presence of elevated
proinflammatory cytokines in depressed or stressed patients. LIMITATIONS:
Heterogeneity of MDD and limited CSF cytokine research complicate the study of
MDD pathogenesis. CONCLUSION: There is significant evidence that inflammatory
processes influence the development and progression of MDD. Future studies with
larger arrays of cytokine profiles aided by neuroimaging may provide more
sensitive and specific modes of diagnostics in determining MDD etiology and
provide guidance in individual therapies.
PMID- 25128862
TI - Endogenous neurogenesis following ischaemic brain injury: insights for
therapeutic strategies.
AB - Ischaemic stroke is among the most common yet most intractable types of central
nervous system (CNS) injury in the adult human population. In the acute stages of
disease, neurons in the ischaemic lesion rapidly die and other neuronal
populations in the ischaemic penumbra are vulnerable to secondary injury.
Multiple parallel approaches are being investigated to develop neuroprotective,
reparative and regenerative strategies for the treatment of stroke. Accumulating
evidence indicates that cerebral ischaemia initiates an endogenous regenerative
response within the adult brain that potentiates adult neurogenesis from
populations of neural stem and progenitor cells. A major research focus has been
to understand the cellular and molecular mechanisms that underlie the
potentiation of adult neurogenesis and to appreciate how interventions designed
to modulate these processes could enhance neural regeneration in the post
ischaemic brain. In this review, we highlight recent advances over the last 5
years that help unravel the cellular and molecular mechanisms that potentiate
endogenous neurogenesis following cerebral ischaemia and are dissecting the
functional importance of this regenerative mechanism following brain injury. This
article is part of a Directed Issue entitled: Regenerative Medicine: the
challenge of translation.
PMID- 25128863
TI - Simultaneous patterning of two different types of nanoparticles into alternating
domains of a striped array of a polymer blend in a single spin-casting step.
AB - A fast and convenient method is developed for simultaneously patterning inorganic
nanoparticles with different optical, electronic or magnetic functionality to
specific surface regions, by spin-casting onto microcontact printed substrates
blend solutions in which the two nanoparticle types are functionalized with
surface polymer brush layers of different surface energies. The process is based
on phase separation of different nanoparticles based on their immiscible brush
layers during spin-casting, with the underlying surface energy heterogeneity of
the patterned substrate directing the different NP types to domains of different
surface energies. Here, we specifically demonstrate the simultaneous localization
of cadmium sulfide quantum dots (CdS QDs), addressed with a surface layer of
polystyrene (PS), and silver nanoparticles (Ag NPs), addressed with a surface
layer of poly(methyl methacrylate) (PMMA), onto the non-polar and polar surface
domains, respectively, of hydrophilic glass patterned with hydrophobic
octadecyltrichlorosilane (OTS) stripe arrays with micron-scale periodicities. In
order to prevent gelation of solvent-swollen polymer-brush coated NPs during spin
casting, which effects strong kinetic constraints on phase separation and
localization, PS, PMMA or PS/PMMA homopolymer blends of sufficiently high Mw were
added to the NP blends to increase the free volume between approaching NPs. The
process parameters were fine-tuned to obtain control over defects in the obtained
patterns.
PMID- 25128865
TI - Phase transition of silica in the TMB-P123-H2O-TEOS quadru-component system: a
feasible route to different mesostructured materials.
AB - Various siliceous structures were obtained using a nonionic block copolymer
(Pluronic P123) surfactant and trimethylbenzene (TMB) as a hydrophobic additive
by hydrolysis and condensation of tetraethoxysilane (TEOS) in a sol-gel process.
The resultant materials were characterized by small-angle X-ray diffraction
(SAXRD), nitrogen adsorption analysis, scanning electron microscopy (SEM) and
transmission electron microscopy (TEM). The results revealed the structure
transformation from hexagonal structure (HEX) to multilamellar vesicles (MLVs)
and then to mesocellular foams (MCFs) in the TMB-P123-H2O-TEOS quadru-component
system. The morphology of the mesoporous silica was mainly controlled by the mass
ratio of TMB/P123 resulted from the increasing volume of the hydrophobic chain of
micelle of P123 that caused by more amount of TMB dissolved in the PPO segment of
polymer. The fact that the occurrence of rod-like particles with curved ends and
the coexistence of the MLVs and the HEX structure indicates that the MLVs are
developed from the ends of HEX structures, rather than formed by a direct
cooperative self-assembly mechanism. Further increasing of packing parameter of
surfactant resulted from TMB addition transforms lamellar micelles to reversed
micelles, leading to the formation of MCFs.
PMID- 25128864
TI - (99m)Tc-labeled aminosilane-coated iron oxide nanoparticles for molecular imaging
of alphanubeta3-mediated tumor expression and feasibility for hyperthermia
treatment.
AB - HYPOTHESIS: Dual-modality imaging agents, such as radiolabeled iron oxide
nanoparticles (IO-NPs), are promising candidates for cancer diagnosis and
therapy. We developed and evaluated aminosilane coated Fe3O4 (10+/-2nm) as a
tumor imaging agent in nuclear medicine through 3-aminopropyltriethoxysilane
(APTES) functionalization. We evaluated this multimeric system of targeted
(99m)Tc-labeled nanoparticles (NPs) conjugated with a new RGD derivate (cRGDfK
Orn3-CGG), characterized as NPs-RGD as a potential thermal therapy delivery
vehicle. EXPERIMENTS: Transmission Electron Microscopy (TEM) and spectroscopy
techniques were used to characterize the IO-NPs indicating their
functionalization with peptides. Radiolabeled IO-NPs (targeted, non-targeted)
were evaluated with regard to their radiochemical, radiobiological and imaging
characteristics. In vivo studies were performed in normal and alphanubeta3
positive tumor (U87MG glioblastoma) bearing mice. We also demonstrated that this
system could reach ablative temperatures in vivo. FINDINGS: Both radiolabeled IO
NPs were obtained in high radiochemical yield (>98%) and proved stable in vitro.
The in vivo studies for both IO-NPs have shown significant liver and spleen
uptake at all examined time points in normal and U87MG glioblastoma tumor-bearing
mice, due to their colloidal nature. We have confirmed through in vivo
biodistribution studies that the non-targeted (99m)Tc-NPs poorly internalized in
the tumor, while the targeted (99m)Tc-NPs-RGD, present 9-fold higher tumor
accumulation at 1h p.i. Accumulation of both IO-NPs in other organs was
negligible. Blocking experiments indicated target specificity for integrin
receptors in U87MG glioblastoma cells. The preliminary in vivo study of applied
alternating magnetic field showed that the induced hyperthermia is feasible due
to the aid of IO-NPs.
PMID- 25128866
TI - The prevalence of cognitive impairment in emergency general surgery.
AB - OBJECTIVES: Rates of all surgical procedures are increasing at a faster rate than
the population is ageing. However, this encouraging statistic, necessitates a
robust evidence base. The epidemiological evidence base in acute general surgery
in the older person is sparse. This is the first assessment of the prevalence of
cognitive impairment measured using the Montreal Cognitive Assessment tool (MoCA)
in acute general surgery. METHODS: In three sites in Wales, England and Scotland
comprising rural and urban populations, we studied consecutive patients aged over
65 years. We considered any older person admitted to the acute general surgical
unit. We assessed them for baseline demographic data. They each underwent a MoCA
assessment. RESULTS: We collected data on 245 people, mean age 76.9 years (8.1,
standard deviation), 136 (55.5%) were women. Of these 201 completed the MoCA
test, mean score of 18.9 and median score 20 (range 0-30). There were 37 (15.1%)
MoCA scores in the normal range (>=26) and 44 (18%) people were unable to attempt
(or complete) the MoCA. Increasing age (p < 0.01) but not sex (p = 0.14)
predicted an abnormal MoCA. Considering only the 44 people who were unable to
attempt the MoCA assessment, 11 (25%) were known to have a diagnosis of dementia,
9 (20.5%) were too unwell and the remainder unable to complete the assessment to
due pre-existing disability. CONCLUSIONS: In a representative UK wide population,
a high proportion of older people admitted with an acute general surgical problem
had cognitive impairment when assessed using the MoCA.
PMID- 25128867
TI - Association of tissue inhibitor of metalloproteinase gene polymorphisms and
unexplained recurrent spontaneous abortions in Han Chinese couples.
AB - OBJECTIVE: To investigate the association of tissue inhibitor of
metalloproteinase (TIMP) gene polymorphisms with unexplained recurrent
spontaneous abortions (URSA) in a well-defined group of Han Chinese couples.
STUDY DESIGN: This is a case-control association study. Genomic DNA was extracted
from peripheral blood samples from 84 couples with histories of three or more
pregnancy losses and 69 age-matched healthy couples with at least one live birth
and no histories of pregnancy loss. Polymerase chain reactions (PCRs) and
sequencing with the fluorescent dye dideoxy-termination method were used to
detect the rs4898 in TIMP-1, rs2277698 in TIMP-2, rs2234921 and rs5749511 in TIMP
3 and rs17035945 in TIMP-4 genotypes and allele frequencies. RESULTS: Neither the
allele frequencies nor any of the genetic model of the five TIMP gene SNPs (i.e.,
TIMP-1-rs4898, TIMP-2-rs2277698, TIMP-3-rs5749511 and rs2234921, and TIMP-4
rs7035945) were significantly differences between the URSA couples and the
control group. CONCLUSIONS: No evidence was found for any associations between
the TIMP-1,-2,-3, or -4 genes SNPs with URSA in this Han Chinese Han.
PMID- 25128868
TI - Evaluation of carbon nanotubes and graphene as reinforcements for UHMWPE-based
composites in arthroplastic applications: A review.
AB - In this review we have evaluated the state of the art of CNT/UHMWPE and
graphene/UHMWPE composites from four different points of view: mechanical
properties, chemical stability, wear resistance and biocompatibility. The
performance of these new carbonaceous composites allows us to conclude that these
materials have overcome a first step on the way to developing into an alternative
to the current HXLPEs used in orthopedic applications.
PMID- 25128869
TI - From single fiber to macro-level mechanics: A structural finite-element model for
elastomeric fibrous biomaterials.
AB - In the present work, we demonstrate that the mesoscopic in-plane mechanical
behavior of membrane elastomeric scaffolds can be simulated by replication of
actual quantified fibrous geometries. Elastomeric electrospun polyurethane (ES
PEUU) scaffolds, with and without particulate inclusions, were utilized.
Simulations were developed from experimentally-derived fiber network geometries,
based on a range of scaffold isotropic and anisotropic behaviors. These were
chosen to evaluate the effects on macro-mechanics based on measurable geometric
parameters such as fiber intersections, connectivity, orientation, and diameter.
Simulations were conducted with only the fiber material model parameters adjusted
to match the macro-level mechanical test data. Fiber model validation was
performed at the microscopic level by individual fiber mechanical tests using
AFM. Results demonstrated very good agreement to the experimental data, and
revealed the formation of extended preferential fiber orientations spanning the
entire model space. We speculate that these emergent structures may be
responsible for the tissue-like macroscale behaviors observed in electrospun
scaffolds. To conclude, the modeling approach has implications for (1) gaining
insight on the intricate relationship between fabrication variables, structure,
and mechanics to manufacture more functional devices/materials, (2) elucidating
the effects of cell or particulate inclusions on global construct mechanics, and
(3) fabricating better performing tissue surrogates that could recapitulate
native tissue mechanics.
PMID- 25128870
TI - Elastic softening of beta-type Ti-Nb alloys by indium (In) additions.
AB - Recent developments showed that beta-type Ti-Nb alloys are good candidates for
hard tissue replacement and repair. However, their elastic moduli are still to be
further reduced to match Young's modulus values of human bone, in order to avoid
stress shielding. In the present study, the effect of indium (In) additions on
the structural characteristics and elastic modulus of Ti-40 Nb was investigated
by experimental and theoretical (ab initio) methods. Several beta-type (Ti-40 Nb)
xIn alloys (with x <= 5.2 wt%) were produced by cold-crucible casting and
subsequent heat treatments (solid solutioning in the beta-field followed by water
quenching). All studied alloys completely retain the beta-phase in the quenched
condition. Room temperature mechanical tests revealed ultimate compressive
strengths exceeding 770 MPa, large plastic strains (>20%) and a remarkable strain
hardening. The addition of up to 5.2 wt% indium leads to a noticeable decrease of
the elastic modulus from 69 GPa to 49 GPa, which is closer to that of cortical
bone (<30 GPa). Young's modulus is closely related to the bcc lattice stability
and bonding characteristics. The presence of In atoms softens the parent bcc
crystal lattice, as reflected by a lower elastic modulus and reduced yield
strength. Ab initio and XRD data agree that upon In substitution the bcc unit
cell volume increases almost linearly. The bonding characteristics of In were
studied in detail, focusing on the energies that appeared from the EDOSs
significant for possible hybridizations. It came out that minor In additions
introduce low energy states with s character that present antibonding features
with the Ti first neighboring atoms as well as with the Ti-Nb second neighboring
atoms thus weakening the chemical bonds and leading to elastic softening. These
results could be of use in the design of low rigidity beta-type Ti-alloys with
non-toxic additions, suitable for orthopedic applications.
PMID- 25128872
TI - Sirtuin 3 interacts with Lon protease and regulates its acetylation status.
AB - Lon is a mitochondrial protease that degrades oxidized damaged proteins, assists
protein folding and participates in maintaining mitochondrial DNA levels. Changes
in Lon mRNA levels, protein levels and activity are not always directly
correlated, suggesting that Lon could be regulated at post translational level.
We found that Lon and SIRT3, the most important mitochondrial sirtuin, colocalize
and coimmunoprecipitate in breast cancer cells, and silencing or inhibition of
Lon did not alter SIRT3 levels. Silencing of SIRT3 increased the levels of Lon
protein and of its acetylation, suggesting that Lon is a target of SIRT3, likely
at K917.
PMID- 25128871
TI - Maternal emotional availability at bedtime and infant cortisol at 1 and 3 months.
AB - BACKGROUND: Previous work has shown that early experience influences infant
cortisol secretion. Few studies, however, have examined associations between
parenting quality and cortisol levels and patterning in very young infants. AIMS:
This study examined linkages between maternal emotional availability (EA) during
a routine caregiving task, bedtime, and infant cortisol in the first 3 months of
life. Concurrent and longitudinal associations between maternal EA and infant
cortisol were examined. STUDY DESIGN: Families were visited when their infants
were 1 and 3 months old. Video equipment was set up in order to record the
infant's bedtime routine. Parents were provided with materials with which to take
saliva samples from their infants at late afternoon, bedtime, and the following
morning. SUBJECTS: At 1 month, participants were 96 mothers and infants living in
a rural U.S. state. Data were available for 88 mothers and infants at 3 months.
OUTCOME MEASURES: Maternal EA was scored from videotapes of bedtime at each age
point. Infant cortisol was assessed from the saliva samples taken by parents.
RESULTS: Regression analyses indicated that at 1 and 3 months of age, infants of
more emotionally available mothers showed lower levels of cortisol secretion
across the night than infants of less emotionally available mothers.
Additionally, multilevel model analyses indicated that infants of more
emotionally available mothers showed greater evidence of a decline in their
cortisol levels across the evening, followed by an increase across the nighttime
into the morning in their cortisol at 3 months. CONCLUSIONS: Findings suggest
that maternal care in the context of a routine caregiving task is associated with
lower stress reactivity and with earlier circadian patterning in very young
infants.
PMID- 25128873
TI - Analysis of (all-E)-lutein and its (Z)-isomers during illumination in a model
system.
AB - Light induced-isomerization of (all-E)-lutein in organic solvent and starch model
systems was investigated. Lutein and its (Z)-isomers were separated by HPLC using
a C30 column and gradient mobile phase based on methanol-methyl-tert-butyl ether
water in 24min. (All-E)-lutein and twelve (Z)-isomers of lutein, in addition a
small amount of (all-E)-zeaxanthin and (9Z, 9'Z)-zeaxanthin were identified by
HPLC-DAD-APCI-MS. Five di-(Z)-luteins were identified for the first time, namely,
(9Z, 9'Z)-, (9Z, 13Z)/(9 Z, 13'Z)-, (13Z, 15Z)- and (9Z, 15Z)-lutein and (9Z,
9'Z)-zeaxanthin. A mixture of (9Z)-lutein and of (9'Z)-lutein was the main
product of the iodine-catalyzed photo-isomerization. (9Z, 13Z)/(9Z, 13'Z)-lutein
were the major di-(Z)-isomers of lutein formed. The susceptibility of lutein to
degradation was much less under dark storage than under lighted storage in starch
model system. Isomerization and degradation of lutein and its (Z)-isomers
proceeded simultaneously in all the model systems.
PMID- 25128874
TI - Analysis of powder phenomena inside a Fette 3090 feed frame using in-line NIR
spectroscopy.
AB - New analytical methods are needed to understand and optimize the processes by
which tablets are produced. Fette 3090 tablet presses are commonly used in the
pharmaceutical industry. A near-infrared (NIR) probe was installed into a Fette
3090 feed frame to understand and monitor the die filling process. The second
objective was to analyze in detail the different factors that could affect the
prediction of the developed NIR calibration models. Two monitoring positions for
NIR spectrometers were evaluated; one at each side of the feed frame. A powder
wave behavior caused by the paddle motion was observed inside the feed frame. The
study also revealed that NIR spectra can help in the understanding of powder flow
inside the feed frame. It was demonstrated that NIR spectra baselines can also be
used to determine changes in mass inside the feed frame. The new NIR method
showed that the paddle wheel speed has a significant impact in the powder
dynamics inside the feed frame. The baselines of the NIR spectra depended on the
mass hold-up inside the feed frame and paddle wheel speed. Studies using blends
were performed to develop a NIR calibration model based on the feed frame system
dynamics to determine acetaminophen drug concentration variability during the die
filling process. The study found that variation in the distance from the powder
to the probe due to paddle wheel speed has a significant effect on the NIR
prediction. This study found that with NIR spectroscopy, blend uniformity can be
assessed with high accuracy during the die filling process using the
corresponding paddle wheel speed in-line calibration model. NIR was demonstrated
to be a good development tool for the in-line monitoring of powder during the die
filling process.
PMID- 25128875
TI - UHPLC-MS/MS method for the determination of the cyclic depsipeptide mycotoxins
beauvericin and enniatins in in vitro transdermal experiments.
AB - Currently, dermal exposure data of cyclic depsipeptide mycotoxins beauvericin and
enniatins are completely absent with a lack of local skin and systemic kinetics,
despite their widespread skin contact and intrinsic hazard. Therefore a sensitive
and specific bioanalytical high-throughput UHPLC-MS/MS method was developed for
the quantitative and simultaneous determination of cyclic depsipeptide mycotoxins
beauvericin and enniatins (A, A1, B, B1, D, E, C/F) in human skin Franz diffusion
cell samples. The limits of detection ranged between 10 and 17pg/ml, while the
total run time was only 4.5min. There was no significant effect of endogenous
skin compounds on the mycotoxin MS signal observed, and the accuracy (0.68-24.68%
bias) and precision (0.57-10.70% RSD) were considered acceptable for our
purposes. Moreover, it was demonstrated that these cyclic depsipeptides are
stable for at least 7 days when formulated in different organic or aqueous
mixtures. Finally, adsorption to glass did occur: at least 50% ethanol or
acetonitrile is required to prevent significant adsorption effects, which could
be as high as 45%.
PMID- 25128876
TI - Identification and quantification of antitumor thioproline and methylthioproline
in Korean traditional foods by a liquid chromatography-atmospheric pressure
chemical ionization-tandem mass spectrometry.
AB - A liquid chromatography-atmospheric pressure chemical ionization-tandem mass
spectrometric method (LC-APCI-MS/MS) has been developed for the sensitive
determination of antitumor thioproline and methylthioproline from fermented
foods. Thioproline and methylthioproline were derivatized in one step with ethyl
chloroformate at room temperature. These compounds were identified and quantified
in various traditional Korean fermented foods by LC-APCI-MS/MS. The concentration
range of thioproline of each food was found for doenjang (0.011-0.032mg/kg),
gochujang (0.010-0.038mg/kg), and ganjang (0.010-0.038mg/kg). Those of
methylthioproline of each food was found for doenjang (0.098-0.632mg/kg),
gochujang (0.015-0.112mg/kg), and ganjang (0.023-1.468mg/kg). A prolonged aging
time leads to an increase in both the thioproline and methylthioproline contents,
suggesting that the storage time plays a key role in the formation of thioproline
and methylthioproline in Korean traditional foods. The results here suggest that
thioproline and methylthioproline are related to the biological activities of
traditional Korean fermented foods.
PMID- 25128877
TI - Acute exercise improves motor memory: exploring potential biomarkers.
AB - We have recently shown that a single bout of acute cardiovascular exercise
improves motor skill learning through an optimization of long-term motor memory.
Here we expand this previous finding, to explore potential exercise-related
biomarkers and their association with measures of motor memory and skill
acquisition. Thirty-two healthy young male subjects were randomly allocated into
either an exercise or control group. Following either an intense bout of cycling
or rest subjects practiced a visuomotor tracking task. Motor skill acquisition
was assessed during practice and retention 1 h, 24 h and 7 days after practice.
Plasma levels of brain-derived neurotrophic factor (BDNF), vascular endothelial
growth factor (VEGF), insulin-like growth factor (IGF-1), epinephrine,
norepinephrine, dopamine and lactate were analyzed at baseline, immediately after
exercise or rest and during motor practice. The exercise group showed
significantly better skill retention 24h and 7 days after acquisition. The
concentration of all blood compounds increased significantly immediately after
exercise and remained significantly elevated for 15 min following exercise except
for BDNF and VEGF. Higher concentrations of norepinephrine and lactate
immediately after exercise were associated with better acquisition. Higher
concentrations of BDNF correlated with better retention 1 h and 7 days after
practice. Similarly, higher concentrations of norepinephrine were associated with
better retention 7 days after practice whereas lactate correlated with better
retention 1h as well as 24 h and 7 days after practice. Thus, improvements in
motor skill acquisition and retention induced by acute cardiovascular exercise
are associated with increased concentrations of biomarkers involved in memory and
learning processes. More mechanistic studies are required to elucidate the
specific role of each biomarker in the formation of motor memory.
PMID- 25128878
TI - Learning pain-related fear: neural mechanisms mediating rapid differential
conditioning, extinction and reinstatement processes in human visceral pain.
AB - BACKGROUND AND AIMS: There exists converging evidence to support a role of pain
related fear in the pathophysiology and treatment of chronic pain conditions.
Pain-related fear is shaped by associative learning and memory processes, which
remain poorly characterized especially in the context of abdominal pain such as
in irritable bowel syndrome (IBS). Therefore, using event-related functional
magnetic resonance imaging (fMRI), we assessed the neural mechanisms mediating
the formation, extinction and reinstatement of abdominal pain-related fear in
healthy humans. Employing painful rectal distensions as clinically-relevant
unconditioned stimuli (US), in this fear conditioning study we tested if
differential excitatory and inhibitory learning is evocable after very few CS-US
learning trials ("rapid conditioning"), and explored the underlying neural
substrates of these learning and memory processes. METHODS: In N=24 healthy men
and women, "rapid" fear acquisition was accomplished by pairing visual
conditioned stimuli (CS(+)) with painful rectal distensions as unconditioned
stimuli (US), while different visual stimuli (CS(-)) were presented without US
(differential delay conditioning with five CS(+) and five CS(-) presentations and
a 80% reinforcement ratio). During extinction, all CS were presented without US.
Subsequently, a reinstatement procedure was implemented, defined as the retrieval
of an extinguished memory after unexpected and unpaired exposure to the US,
followed by CS presentations. For each phase, changes in perceived CS-US
contingency and CS unpleasantness were assessed with visual analogue scales and
compared with analyses of variance. fMRI data were analyzed using whole-brain
analyses (at p<.001 uncorrected) and in regions-of-interest analyses with
familywise error correction of alpha (pFWE<.05). Differential neural activation
in response to the CS during each experimental phase (i.e., CS(+)>CS(-);
CS(+)7.5 L/kg), suggesting that CNTs can act as strong sorbents under a wide range
of conditions.
PMID- 25128884
TI - Accuracy of mixing models in predicting sediment source contributions.
AB - Determining the source of sediment using geochemical properties is now a widely
used approach in catchment management. However the outcome of these studies often
depends on the type of model used to determine the relative contribution from
difference sources. Here we test the accuracy and robustness of four widely used
sediment mixing models using artificial mixtures of three well-distinguished
geologic sources. Sub-samples from these three sources were mixed to create four
groups of samples, each consisting of five samples, with known source
contributions, 20 samples in total. The source contributions to the individual
and groups of artificial sediment mixtures were calculated using each of the four
mixing models: Modified Hughes, Modified Collins, Landwehr and Distribution
models. Unlike Modified Collins and Landwehr models which use calculated values
from each tracer property of individual sources (e.g. mean and standard
deviation), Hughes model uses the measured fingerprint property of replicated
samples from each source and Distribution model incorporate distribution of
tracers and correlation between tracer properties for sediment samples and
sources. For the 20 individual sample mixtures the Distribution model provided
the closest estimates to the known sediment source contribution values (Mean
Absolute Error (MAE)=10.8%, and standard error (SE)=0.9%). The Modified Hughes
(MAE=13.5%, SE=1.1%), Landwehr (MAE=19%, SE=1.7) and Collins models (MAE=29%,
SE=2.1%) were the next accurate models, respectively. For the groups of the
samples the Modified Hughes was the most robust source contribution predictor
with 5.4% error. The Distribution model (MAE=6.1%) and Landwehr model (MAE=7.8%)
were the second and third accurate models. Collins model with MAE of 28.3% was a
significantly weaker source contribution predictor than the three other models.
This study demonstrates the dependence of source attribution on model selection.
The study highlight the need to test mixing model using known source and mixture
samples prior to applying them to field samples. The results indicate that the
Distribution and Modified Hughes models provided the most accurate source
attributions using geochemical fingerprint properties.
PMID- 25128885
TI - Evaluation of the transfer of soil arsenic to maize crops in suburban areas of
San Luis Potosi, Mexico.
AB - The presence of arsenic (As) in agricultural food products is a matter of concern
because it can cause adverse health effects at low concentrations. Agricultural
product intake constitutes a principal source for As exposure in humans. In this
study, the contribution of the chemical-soil parameters in As accumulation and
translocation in the maize crop from a mining area of San Luis Potosi was
evaluated. The total arsenic concentration and arsenic speciation were determined
by HG-AFS and IC-HG-AFS, respectively. The data analysis was conducted by cluster
analysis (CA) and principal component analysis (PCA). The soil pH presented a
negative correlation with the accumulated As in each maize plant part, and
parameters such as iron (Fe) and manganese (Mn) presented a higher correlation
with the As translocation in maize. Thus, the metabolic stress in maize may
induce organic acid exudation leading a higher As bioavailability. A high As
inorganic/organic ratio in edible maize plant tissues suggests a substantial risk
of poisoning by this metalloid. Careful attention to the chemical changes in the
rhizosphere of the agricultural zones that can affect As transfer through the
food chain could reduce the As-intoxication risk of maize consumers.
PMID- 25128886
TI - Estimation of uncertainty in the sampling and analysis of polychlorinated
biphenyls and polycyclic aromatic hydrocarbons from contaminated soil in
Brighton, UK.
AB - The heterogeneity of environmental samples is increasingly recognised, yet rarely
examined in organic contamination investigations. In this study soil samples from
an ex-landfill site in Brighton, UK were analysed for polychlorinated biphenyl
(PCB) and polycyclic aromatic hydrocarbon (PAH) contamination by using a balanced
sampling protocol. The analytical technique of gas chromatography-mass
spectrometry was found to be fit for purpose by the use of duplicate samples and
the statistical analysis of variances, as well as of certified reference
materials. The sampling uncertainty was found to significantly overweigh the
analytical uncertainty, by a factor of 3 and 6 for PCBs and PAHs, respectively.
The soil samples showed a general trend of PCB concentration that was under the
recommended target level of 20 ng/g dry weight. It is possible that one site
alongside the main road may exceed the 20 ng/g target level, after taking into
consideration the overall measurement uncertainty (70.8%). The PAH contamination
was more severe, with seven sites potentially exceeding the effect-range medium
concentrations. The soil samples with relatively high PCB and PAH concentrations
were all taken from the grass verge, which also had the highest soil organic
carbon content. The measurement uncertainty which was largely due to sampling can
be reduced by sampling at a high resolution spacing of 17 m, which is recommended
in future field investigations of soil organic contamination.
PMID- 25128887
TI - Farmer and retailer knowledge and awareness of the risks from pesticide use: a
case study in the Wei River catchment, China.
AB - Monitoring the educational level of farmers and retailers on pesticide use would
be useful to assess the appropriateness of information for reducing or/and
avoiding the risks from pesticides in rural regions. The levels of knowledge and
awareness of the dangers to the environment and human health were investigated by
questionnaires for farmers (209) and retailers (20) in two rural regions
(Qianyang County (S1) and Chencang County (S2)) of the Wei River catchment in
China where the modes of farming and the state of erosion are very different. The
results showed that farmers learned the use and dangers of pesticides mainly by
oral communication (p<0.01). Protective measures were inadequate; 65% (S1) and
55% (S2) of farmers never used any protective measures during spraying (p<0.05).
Washing hands (>70%) was the most common mode of personal hygiene, relative to
wearing masks, showering, and changing clothes, but no significant differences
were observed between the selected regions. Most pesticide wastes were dumped
directly onto the land or into water, suggesting that educational measures should
be taken to address the potential risks from the residues in the wastes. Over 85%
of farmers (S1 and S2) claimed to use illegal pesticides, but the reasons for
their use varied (p<0.01). Retailers were well-informed and highly conscious of
their responsibility for the safe use of pesticides, especially in S2 (p<0.01). A
canonical correspondence analysis indicated that educational level and age
differed between the two regions and contributed greatly to the risks from
pesticide use (p<0.01). Educational programmes targeted to age groups, proper
disposal of pesticide waste, and sufficient supervision from authorities should
consequently be considered for improving the levels of knowledge and awareness of
the dangers of pesticides to human health and environmental pollution in the Wei
River catchment, China.
PMID- 25128888
TI - Occurrence of antibiotics in the aquatic environment of Jianghan Plain, central
China.
AB - The occurrence of 19 antibiotics (sulfonamide, fluoroquinolone, tetracycline and
macrolide) was studied in surface water and groundwater samples collected from
Shahu County of Jianghan Plain, central China, in autumn (dry season) and spring
(wet season). In autumn, chlorotetracycline, doxycycline and enrofloxacin were
the three antibiotics with the highest concentrations and high relevance ratios
in all of the water samples. The concentration of chlorotetracycline was greatest
in surface water at 122.3 n gL(-1) and was as high as 86.6 ng L(-1) in
groundwater, which are among the highest values reported worldwide. In spring,
tetracycline was found to be more than 100 ng L(-1) in groundwater and surface
water, which also contained high concentrations of ofloxacin (135.1 ng L(-1)),
norfloxacin (134.2 ng L(-1)) and erythromycin dehydrate (381.5 ng L(-1)). Most of
the SMs were observed at higher detection frequencies in spring than in autumn,
which can be ascribed to surface runoff by rain water during the wet season
(spring). The average concentrations of compounds in the fluoroquinolone and
tetracycline categories were far higher than those in the sulfonamide and
macrolide categories, which had concentrations of less than 16 ng L(-1) in
groundwater (except erythromycin dehydrate), while macrolides were found in all
samples, except erythromycin dehydrate. The main antibiotics present in
groundwater were also the dominant compounds found in surface water, with
correlation coefficients of 0.93 and 0.97 in autumn and spring, respectively,
indicating the potential contamination of groundwater by the infiltration of
contaminated surface water.
PMID- 25128889
TI - Fluorine distribution in soil in the vicinity of an accidental spillage of
hydrofluoric acid in Korea.
AB - This study assessed the status of fluorine (F) in soil in the vicinity of a
spillage of anhydrous hydrofluoric acid in Korea. Gaseous hydrogen fluoride
dispersed was suspected to have contaminated the surrounding soil environment.
Total and water soluble F concentrations in soil within a 1 km radius of the
spillage were determined. Total F concentrations (mean=222+/-70.1 mg kg(-1)) were
lower than the Korean limit value (i.e., 400 mg kg(-1)) and several reported
measurements of background F concentrations in soils except for a single outlying
case. Soluble F concentrations ranged from 0.111 to 6.40 mg kg(-1) (mean=2.20+/
1.80 mg kg(-1)). A negative correlation between the soluble F concentration of
soil and distance from the spillage was observed. This indicates that the soluble
F concentration has a crucial role in fractionating the F concentration arising
from a 'non natural input' i.e., the spillage. The F content of rice samples
seemed to be significantly influenced by the soluble F concentrations of soils.
Rice samples collected from the control and affected areas contained 41 mg kg(-1)
and 578 mg kg(-1) of total F, respectively.
PMID- 25128890
TI - Stereoselective quantitation of haloxyfop in environment samples and
enantioselective degradation in soils.
AB - The chiral separation of haloxyfop enantiomers was first performed on (R, R)
Whelk-O1 chiral column (pirkle type) by high-performance liquid chromatography
(HPLC). Chromatographic conditions such as mobile phase composition and column
temperature were optimized, and the best resolution was obtained using hexane/n
propanol (98/2) with Rs value of 3.43. Chiral residue analysis methods for
haloxyfop enantiomers in environmental matrices, such as soil and water, were
developed with recoveries ranging from 85.95% to 104.25%. The results showed that
these methods were effective enough for detecting the residual enantiomers
environmental matrices. The behavior of haloxyfop in four soils was studied and
the enantioselective degradation was found with enantiomer fraction values
ranging from 0.058 to 0.61. The research work was extremely useful for
investigating the fate of individual enantiomers in environment, the mechanism of
the stereoselective behaviors, and the risk assessment of chiral pesticide.
PMID- 25128891
TI - Interaction mechanisms between organic UV filters and bovine serum albumin as
determined by comprehensive spectroscopy exploration and molecular docking.
AB - Organic UV filters are a group of emerging PPCP (pharmaceuticals and personal
care products) contaminants. Current information is insufficient to understand
the in vivo processes and health risks of organic UV filters in humans. The
interaction mechanism of UV filters with serum albumin provides critical
information for the health risk assessment of these active ingredients in
sunscreen products. This study investigates the interaction mechanisms of five
commonly used UV filters (2-hydroxy-4-methoxybenzophenone, BP-3; 2-ethylhexyl 4
methoxycinnamate, EHMC; 4-methylbenzylidene camphor, 4-MBC;
methoxydibenzoylmethane, BDM; homosalate, HMS) with bovine serum albumin (BSA) by
spectroscopic measurements of fluorescence, circular dichroism (CD), competitive
binding experiments and molecular docking. Our results indicated that the
fluorescence of BSA was quenched by these UV filters through a static quenching
mechanism. The values of the binding constant (Ka) ranged from (0.78+/
0.02)*10(3) to (1.29+/-0.01)*10(5) L mol(-1). Further exploration by synchronous
fluorescence and CD showed that the conformation of BSA was demonstrably changed
in the presence of these organic UV filters. It was confirmed that the UV filters
can disrupt the alpha-helical stability of BSA. Moreover, the results of
molecular docking revealed that the UV filter molecule is located in site II (sub
domain IIIA) of BSA, which was further confirmed by the results of competitive
binding experiments. In addition, binding occurred mainly through hydrogen
bonding and hydrophobic interaction. This study raises critical concerns
regarding the transportation, distribution and toxicity effects of organic UV
filters in human body.
PMID- 25128892
TI - Photochemical transformation of phenylurea herbicides in surface waters: a model
assessment of persistence, and implications for the possible generation of
hazardous intermediates.
AB - This work models the phototransformation kinetics in surface waters of five
phenylurea herbicides (diuron, fenuron, isoproturon, metoxuron and chlortoluron),
for which important photochemical parameters are available in the literature
(direct photolysis quantum yields and reaction rate constants with .OH, CO3(-.)
and the triplet states of chromophoric dissolved organic matter, (3)CDOM*). Model
calculations suggest that isoproturon and metoxuron would be the least
photochemically persistent and diuron the most persistent compound. Reactions
with .OH and (3)CDOM* would be the main phototransformation pathways for all
compounds in the majority of environmental conditions. Reaction with CO3(-) could
be important in waters with low dissolved organic carbon (DOC), while direct
photolysis would be negligible for fenuron, quite important for chlortoluron, and
somewhat significant for the other compounds. The direct photolysis of metoxuron
and diuron is known to increase toxicity, and such a photoreaction pathway would
be enhanced at intermediate DOC values (1-4 mg C L(1)). The reaction between
phenylureas and .OH is known to produce toxic intermediates, differently from
(3)CDOM*. Therefore, the shift of reactivity from .OH to (3)CDOM* with increasing
DOC could reduce the environmental impact of photochemical transformation.
PMID- 25128893
TI - Engineered nanoparticles and organic matter: a review of the state-of-the-art.
AB - Growth in the development and production of engineered nanoparticles (ENPs) in
recent years has increased the potential for interactions of these nanomaterials
with aquatic and terrestrial environments. Carefully designed studies are
therefore required in order to understand the fate, transport, stability, and
toxicity of nanoparticles. Natural organic matter (NOM), such as the humic
substances found in water, sediment, and soil, is one of the substances capable
of interacting with ENPs. This review presents the findings of studies of the
interaction of ENPs and NOM, and the possible effects on nanoparticle stability
and the toxicity of these materials in the environment. In addition, ENPs and NOM
are utilized for many different purposes, including the removal of metals and
organic compounds from effluents, and the development of new electronic sensors
and other devices for the detection of active substances. Discussion is therefore
provided of some of the ways in which NOM can be used in the production of
nanoparticles. Although there has been an increase in the number of studies in
this area, further progress is needed to improve understanding of the dynamic
interactions between ENPs and NOM.
PMID- 25128894
TI - Sensitive amperometric determination of methimazole based on the electrocatalytic
effect of rutin/multi-walled carbon nanotube film.
AB - Electrochemical deposition was used to prepare a glassy carbon electrode modified
with multi-walled carbon nanotubes and the glycosidic compound, rutin
(R/MWCNTs/GCE). Cyclic voltammetry of the modified electrode in aqueous solution
(pH8) showed a pair of well-defined, stable and reversible redox peaks with
surface confined characteristics. The catechol moiety of rutin produced the
voltammetric peaks via a 2 electron, 2 proton mechanism in the range of 0.0-0.4V
(vs. Ag/AgCl). The transfer coefficient (alpha), heterogeneous electron transfer
rate constant (ks), and surface concentration (Gamma) for R/MWCNTs/GCE were
calculated by using the cyclic voltammetric data. The modified electrode showed
excellent catalytic activity toward oxidation of methimazole. Fixed-potential
amperometry was used for sub-micromolar determination of methimazole at pH8.
Linear dependence of anodic current to methimazole concentration was obtained in
the range of 0.1-26MUM of the drug with a limit of detection at 18nM. The
modified electrode retained its initial response for at least 2weeks if stored in
dry ambient conditions. The electrode was used for the amperometric determination
of methimazole in formulations and spiked blood serum samples, successfully.
PMID- 25128895
TI - Nano-cerium vanadate: a novel inorganic ion exchanger for removal of americium
and uranium from simulated aqueous nuclear waste.
AB - Cerium vanadate nanopowders were synthesized by a facile low temperature co
precipitation method. The product was characterized by X-ray diffraction and
transmission electron microscopy and found to consist of ~25 nm spherical
nanoparticles. The efficiency of these nanopowders for uptake of alpha-emitting
radionuclides (233)U (4.82 MeV alpha) and (241)Am (5.49 MeV alpha, 60 keV gamma)
has been investigated. Thermodynamically and kinetically favorable uptake of
these radionuclides resulted in their complete removal within 3h from aqueous
acidic feed solutions. The uptake capacity was observed to increase with increase
in pH as the zeta potential value decreased with the increase in pH but effect of
ionic strength was insignificant. Little influence of the ions like Sr(2+),
Ru(3+), Fe(3+), etc., in the uptake process indicated CeVO4 nanopowders to be
amenable for practical applications. The isotherms indicated predominant uptake
of the radioactive metal ions in the solid phase of the exchanger at lower feed
concentrations and linear Kielland plots with positive slopes indicated favorable
exchange of the metal ions with the nanopowder. Performance comparison with the
other sorbents reported indicated excellent potential of nano-cerium vanadate for
removing americium and uranium from large volumes of aqueous acidic solutions.
PMID- 25128896
TI - Removal of trace mercury(II) from aqueous solution by in situ formed Mn-Fe
(hydr)oxides.
AB - The efficiency and mechanism of trace mercury (Hg(II)) removal by in situ formed
manganese-ferric (hydr)oxides (in situ Mn-Fe) were investigated by reacting KMnO4
with Fe(II) in simulated solutions and natural water. In the simulated solutions,
the impact of coagulant dosage, pH, and temperature on mercury removal was
studied. Experimental results showed that in situ Mn-Fe more effectively removed
mercury compared with polyaluminum chloride (PAC) and iron(III) chloride (FeCl3),
and that mercury existed in the form of uncharged species, namely Hg(OH)2,
HgClOH(aq), and HgCl2(aq). Fourier transform infrared spectroscopy demonstrated
that in situ Mn-Fe contained hydroxyl groups as the surface active sites, while X
ray photoelectron spectroscopy (XPS) measurements revealed that MnO2 or MnOOH and
FeOOH were the dominant species in the precipitates. XPS analysis indicated that
an Hg-Mn-Fe mixture was formed in the precipitates, suggesting that mercury was
removed from solutions via transfer from the liquid phase to solid phase. These
results indicated that the primary mercury removal mechanisms in in situ Mn-Fe
were surface complexation and flocculation-precipitation processes. Satisfactory
removal efficiency of mercury was also observed following in situ Mn-Fe in
natural waters.
PMID- 25128897
TI - Influenza virus-like particle vaccines made in Nicotiana benthamiana elicit
durable, poly-functional and cross-reactive T cell responses to influenza HA
antigens.
AB - Cell-mediated immunity plays a major role in long-lived, cross-reactive
protection against influenza virus. We measured long-term poly-functional and
cross-reactive T cell responses to influenza hemagglutinin (HA) elicited by a new
plant-made Virus-Like Particle (VLP) vaccine targeting either H1N1
A/California/7/09 (H1) or H5N1 A/Indonesia/5/05 (H5). In two independent clinical
trials, we characterized the CD4(+) and CD8(+) T cell homotypic and heterotypic
responses 6 months after different vaccination regimens. Responses of VLP
vaccinated subjects were compared with placebo and/or a commercial trivalent
inactivated vaccine (TIV:FluzoneTM) recipients. Both H1 and H5 VLP vaccines
elicited significantly greater poly-functional CD4(+) T cell responses than
placebo and TIV. Poly-functional CD8(+) T cell responses were also observed after
H1 VLP vaccination. Our results show that plant-made HA VLP vaccines elicit both
strong antibody responses and poly-functional, cross-reactive memory T cells that
persist for at least 6 months after vaccination.
PMID- 25128898
TI - A dorsal-pathway account of aphasic language production: the WEAVER++/ARC model.
AB - It has long been assumed that a dorsal pathway running from temporal to inferior
frontal cortex underpinned by the left arcuate fasciculus (AF) underlies both
repetition and spoken language production. However, according to a recent
proposal, a ventral pathway underpinned by extreme capsule (EmC) and uncinate
fasciculus (UF) fiber tracts is primarily responsible for language production,
whereas the AF primarily underlies repetition. Here, a computational
implementation of the dorsal-pathway account of language production is presented,
called WEAVER++/ARC (for WEAVER++ Arcuate Repetition and Conversation), which
synthesizes behavioral psycholinguistic, functional neuroimaging, and
tractographic evidence. The results of computer simulations revealed that the
model accounts for the typical patterns of impaired and spared language
performance associated with classic acute-onset and progressive aphasias.
Moreover, the model accounts for recent evidence that damage to the AF but not
the EmC/UF pathway predicts impaired production performance. It is concluded that
the results demonstrate the viability of a dorsal-pathway account of language
production.
PMID- 25128900
TI - Mangostanaxanthones I and II, new xanthones from the pericarp of Garcinia
mangostana.
AB - Two new xanthones: mangostanaxanthones I (3) and II (5) were isolated from the
pericarp of Garcinia mangostana, along with four known xanthones: 9
hydroxycalabaxanthone (1), parvifolixanthone C (2), alpha-mangostin (4), and
rubraxanthone (6). Their structures were elucidated on the basis of IR, UV, 1D,
2D NMR, and MS spectroscopic data, in addition to comparison with literature
data. The isolated compounds were evaluated for their antioxidant, antimicrobial,
and quorum-sensing inhibitory activities. Compounds 3 and 5 displayed promising
antioxidant activity with IC50 12.07 and 14.12 MUM, respectively using DPPH
assay. Compounds 4-6 had weak to moderate activity against Escherichia coli and
Staphylococcus aureus, while demonstrated promising action against Bacillus
cereus with MICs 0.25, 1.0, and 1.0mg/mL, respectively. The tested compounds were
inactive against Candida albicans. However, they showed selective antifungal
potential toward Aspergillus fumigatus. Compounds 3 and 4 possessed quorum
sensing inhibitory activity against Chromobacterium violaceum ATCC 12472.
PMID- 25128899
TI - Molecular aspects of tight junction barrier function.
AB - In complex multicellular organisms, epithelia lining body cavities regulate
absorption and secretion of ions, organic molecules, and water. Proper function
of epithelia depends on apically and basolaterally situated ion channels as well
as tight junctions which seal the apical intercellular space. Without tight
junctions, transepithelial concentration gradients of ions and nutrients would be
dissipated through the paracellular space. Elevated tight junction permeability
is a feature of many diseases of multiple organs, including the gastrointestinal
tract [1,2,3(*),4(*)], kidney [5,6], and lungs [7,8]. In the intestines,
epithelial barrier dysfunction is a major contributor to diarrhea and
malnutrition and is associated with significant morbidity and mortality
worldwide.
PMID- 25128901
TI - Biphenyls from Nicotiana tabacum and their anti-tobacco mosaic virus.
AB - Five new biphenyls, tababiphenyls A-E (1-5), together with five known ones (5
10), were isolated from the leaves of Nicotiana tabacum, of which compound 1
possessed a seldom reported 6-carbons unit in biphenyls. Their structures were
established on the basis of extensive spectroscopic analyses. All compounds were
tested for their anti-tobacco mosaic virus (anti-TMV) activities. The results
showed that compounds 3 and 5 exhibited high anti-TMV activities with inhibition
rate of 48.4% and 32.1%, respectively, which were higher than that of positive
control (ningnanmycin). The other compounds also showed potential anti-TMV
activities with inhibition rates in the range of 18.6-28.7%, respectively.
PMID- 25128902
TI - Investigating driver willingness to drive through flooded waterways.
AB - Approximately 40% of all drowning deaths involve a motor vehicle. Regardless of
its significance as a cause of flood-related mortality, there is continued
prevalence of driving through flooded waterways in Australia and worldwide. We
aimed to understand the motivational determinates of driving through flooded
waterways in low and high-risk scenarios by utilizing an augmented theory of
planned behaviour (TPB) with behavioural willingness as the outcome variable as
well as the influence of additional predictors; namely perceived risk and past
behaviour. Participants (n=174; Mage=27.43, SD=10.76) answered standard TPB-based
questions in regards to attitudes, subjective norm, and perceived behavioural
control (PBC), as well as additional variables of perceived risk (i.e., perceived
susceptibility and perceived severity) and past behaviour. Support was found for
the augmented TPB as attitude, subjective norm, and PBC predicted behavioural
willingness. Support was also found for perceived severity in the high-risk but
not the low-risk scenario. No support was found for perceived susceptibility.
Past behaviour emerged as a significant predictor of willingness in the low and
high-risk scenario. The findings provide support for an augmented TPB in
understanding individuals' willingness to drive through flooded waterways,
suggesting that a multi-strategy approach may be critical in attempts to reduce
the incidence of such risky driving behaviour.
PMID- 25128903
TI - A human experimental model of episodic pain.
AB - An experimental model of daily episodic pain was developed to investigate
peripheral sensitization and cortical reorganization in healthy individuals. Two
experiments (A and B) were conducted. Experiments A and B consisted of one and
five consecutive days, respectively, in which the participants were subjected to
45 min of intense painful cutaneous electrical stimulation (episodic pain
session), using a stimulus paradigm that in animals has been shown to induce long
term potentiation. These electrical stimulations produced a verbal pain rating of
approximately 85 on a 0-100 verbal rating scale (VRS). Physiological (blood flow
and axon flare reflex), psychophysical (perception threshold and verbal pain
ratings) and electrophysiological (128 channels recorded somatosensory evoked
potential (SEP)) measurements were recorded. The stimulation evoked a visible
axon flare reflex and caused significantly increased cutaneous blood flow around
the site of the stimulation. Axon flare reflex and blood flow reached a plateau
on day one in all the subjects and no significant changes between the days were
observed. The results showed that the effect of the electrical stimulations
changed over the five days; pain potentiation was induced on the first day
(significant increase in the verbal pain ratings during the 45 min stimulation)
but not on any of the subsequent days. After five days of subsequent pain
induction, the global field power showed a significant reduction in P2 amplitude
in the late stage (200-370 ms, in the central-parietal area). In conclusion, the
results suggest that in healthy individuals this model of episodic pain produces
a rapid adaptation after day one and that generates significant SEP changes at
day five.
PMID- 25128905
TI - Fusing transcriptomics to progressive prostate cancer.
AB - This commentary highlights the article by Yu et al, describing a set of novel
fusion transcripts strongly associated with prostate cancer prognosis.
PMID- 25128904
TI - Phoneme-free prosodic representations are involved in pre-lexical and lexical
neurobiological mechanisms underlying spoken word processing.
AB - Recently we reported that spoken stressed and unstressed primes differently
modulate Event Related Potentials (ERPs) of spoken initially stressed targets.
ERP stress priming was independent of prime-target phoneme overlap. Here we test
whether phoneme-free ERP stress priming involves the lexicon. We used German
target words with the same onset phonemes but different onset stress, such as
MANdel ("almond") and manDAT ("mandate"; capital letters indicate stress). First
syllables of those words served as primes. We orthogonally varied prime-target
overlap in stress and phonemes. ERP stress priming did neither interact with
phoneme priming nor with the stress pattern of the targets. However, polarity of
ERP stress priming was reversed to that previously obtained. The present results
are evidence for phoneme-free prosodic processing at the lexical level. Together
with the previous results they reveal that phoneme-free prosodic representations
at the pre-lexical and lexical level are recruited by neurobiological spoken word
recognition.
PMID- 25128908
TI - MRI criteria for the diagnosis of pleomorphic adenoma: a validation study.
AB - OBJECTIVES: To validate an MRI algorithm characteristic of pleomorphic adenoma
(PA). STUDY DESIGN: Cross-sectional analysis. SETTING: Academic tertiary-care
medical center. METHODS: A radiologic algorithm for the MRI diagnosis of PA was
developed on the basis of five "high probability" criteria that all must be
fulfilled for the MRI to qualify as a positive test result: bright T2-signal,
sharp margins, heterogeneous nodular enhancement, lobulated contours, T2-dark
rim. We then identified MRI images from our institutional database to test the
diagnostic accuracy of the proposed algorithm. RESULTS: A total of 103
parotidectomy cases with adequate MRI studies were identified (pleomorphic
adenoma n=41, mucoepidermoid carcinoma n=11, Warthin's tumor n=8, adenoid cystic
carcinoma n=6, oncocytoma n=6, acinic cell carcinoma n=5, salivary duct carcinoma
n=5, and other n=21). Eighteen of 21 cases that met all five "high probability"
MRI criteria were consistent with PA on final histopathology; 3 were consistent
with carcinoma. MRI had a specificity of 95.1% [95% confidence interval: 85.6
98.7%] and sensitivity of 43.9% [95% C.I.: 28.8-60.1%] for PA. The positive
predictive value was 85.7% [95% C.I.: 70.4-100%] and the negative predictive
value was 71.9% [95% C. I.: 62.0-81.9%]. The overall diagnostic accuracy was
74.8% [95% C.I.: 66.2-83.3%]. CONCLUSION: A "high probability" MRI is about 95%
specific for pleomorphic adenoma. A subset of patients with MRI imaging that is
highly suggestive of PA may reliably avoid further workup. The value of MRI in
this setting is especially useful if preoperative fine needle aspiration is not
readily available. A significant proportion of PAs, however, have indeterminate
imaging features that overlap considerably with other benign and malignant
lesions.
PMID- 25128906
TI - Lung cancer transcriptomes refined with laser capture microdissection.
AB - We evaluated the importance of tumor cell selection for generating gene
signatures in non-small cell lung cancer. Tumor and nontumor tissue from
macroscopically dissected (Macro) surgical specimens (31 pairs from 32 subjects)
was homogenized, extracted, amplified, and hybridized to microarrays. Adjacent
scout sections were histologically mapped; sets of approximately 1000 tumor cells
and nontumor cells (alveolar or bronchial) were procured by laser capture
microdissection (LCM). Within histological strata, LCM and Macro specimens
exhibited approximately 67% to 80% nonoverlap in differentially expressed (DE)
genes. In a representative subset, LCM uniquely identified 300 DE genes in tumor
versus nontumor specimens, largely attributable to cell selection; 382 DE genes
were common to Macro, Macro with preamplification, and LCM platforms. RT-qPCR
validation in a 33-gene subset was confirmatory (rho = 0.789 to 0.964, P = 0.0013
to 0.0028). Pathway analysis of LCM data suggested alterations in known cancer
pathways (cell growth, death, movement, cycle, and signaling components), among
others (eg, immune, inflammatory). A unique nine-gene LCM signature had higher
tumor-nontumor discriminatory accuracy (100%) than the corresponding Macro
signature (87%). Comparison with Cancer Genome Atlas data sets (based on
homogenized Macro tissue) revealed both substantial overlap and important
differences from LCM specimen results. Thus, cell selection via LCM enhances
expression profiling precision, and confirms both known and under-appreciated
lung cancer genes and pathways.
PMID- 25128907
TI - Re-testing and misclassification of HIV-2 and HIV-1&2 dually reactive patients
among the HIV-2 cohort of the West African Database to evaluate AIDS
collaboration.
AB - INTRODUCTION: West Africa is characterized by the circulation of HIV-1 and HIV-2.
The laboratory diagnosis of these two infections as well as the choice of a first
line antiretroviral therapy (ART) is challenging, considering the limited access
to second-line regimens. This study aimed at confirming the classification of HIV
2 and HIV-1&2 dually reactive patients followed up in the HIV-2 cohort of the
West African Database to evaluate AIDS collaboration. METHOD: A cross-sectional
survey was conducted from March to December 2012 in Burkina Faso, Cote d'Ivoire
and Mali among patients classified as HIV-2 or HIV-1&2 dually reactive according
to the national HIV testing algorithms. A 5-ml blood sample was collected from
each patient and tested in a single reference laboratory in Cote d'Ivoire
(CeDReS, Abidjan) with two immuno-enzymatic tests: ImmunoCombII(r) (HIV-1&2
ImmunoComb BiSpot - Alere) and an in-house ELISA test, approved by the French
National AIDS and hepatitis Research Agency (ANRS). RESULTS: A total of 547
patients were included; 57% of them were initially classified as HIV-2 and 43% as
HIV-1&2 dually reactive. Half of the patients had CD4>=500 cells/mm(3) and 68.6%
were on ART. Of the 312 patients initially classified as HIV-2, 267 (85.7%) were
confirmed as HIV-2 with ImmunoCombII(r) and in-house ELISA while 16 (5.1%) and 9
(2.9%) were reclassified as HIV-1 and HIV-1&2, respectively (Kappa=0.69;
p<0.001). Among the 235 patients initially classified as HIV-1&2 dually reactive,
only 54 (23.0%) were confirmed as dually reactive with ImmunoCombII(r) and in
house ELISA, while 103 (43.8%) and 33 (14.0%) were reclassified as HIV-1 and HIV
2 mono-infected, respectively (kappa= 0.70; p<0.001). Overall, 300 samples
(54.8%) were concordantly classified as HIV-2, 63 (11.5%) as HIV-1&2 dually
reactive and 119 (21.8%) as HIV-1 (kappa=0.79; p<0.001). The two tests gave
discordant results for 65 samples (11.9%). CONCLUSIONS: Patients with HIV-2 mono
infection are correctly discriminated by the national algorithms used in West
African countries. HIV-1&2 dually reactive patients should be systematically
investigated, with a standardized algorithm using more accurate tests, before
initiating ART as at least 4 out of 10 of them could initiate an effective first
line ART for HIV-1 and optimize their second-line treatment options.
PMID- 25128909
TI - Incidental papillary thyroid carcinoma: clinical characteristics and prognostic
factors among patients with Graves' disease and euthyroid goiter, Cleveland
Clinic experience.
AB - OBJECTIVE: The prevalence and clinical significance of incidental differentiated
thyroid cancer (DTC) in patients with Graves' disease (GD) remain uncertain.
Thyroid stimulating antibody (TSI Ab)-titers were thought to be responsible for
the potentially increased incidence or aggressiveness of PTC in that setting. The
aim of this study was to compare the prevalence of incidental DTC among patients
with GD and euthyroid goiter (EG), to assess the ability of TSI to predict DTC in
GD and to investigate the clinical features that may predict incidental DTC in GD
and EG. METHODS: Two hundred and forty eight patients with EG and 245 patients
with GD patients who had undergone total thyroidectomy at our institution between
2005 and 2013 were retrospectively selected from our data base. An analysis of
incidentally discovered DTC was conducted comparing GD group with EG group.
RESULTS: Incidental micro-papillary thyroid cancer (MPTC) was found in 28% in EG
group, as compared to 26% in GD group. PTC Patients with GD were significantly
younger (44 vs 59) and less likely to have compressive symptoms than with EG
before surgery (p<0.001). In GD group, patients with MPTC were also significantly
older (p=0.009) than those without, were more likely to have symptomatic goiter
(p<0.001), and to have a nodular disease (p<0.001). TSI ab titer did not predict
MPTC in GD group (The AUC curve was 0.55 (95% CI: 0.46, 0.64). Among patients
with GD and incidental MPTC, 58% of patients had at least one nodule. CONCLUSION:
The prevalence of incidental DTC in GD is comparable to EG. Each is increased
compared to general population. Age of presentation of PTC was significantly
lower in GD suggesting an increased risk for MPTC in GD. Nodule size greater than
1cm predicted incidental DTC whereas TSI ab titers and disease duration did not.
PMID- 25128910
TI - Elective single versus double embryo transfer: live birth outcome and patient
acceptance in a prospective randomised trial.
AB - The purpose of this study was to determine which strategy of embryo transfer has
a better trade-off in live birth delivery rate versus multiple pregnancy
considering patient acceptance: elective single embryo transfer (eSET) or
elective double embryo transfer (eDET). In all, 199 women <38 years of age
undergoing their first IVF treatment in a private centre were included in a
prospective open-label randomised controlled trial. Patients were randomised into
four groups: (1) eSET on Day 3; (2) eSET on Day 5; (3) eDET on Day 3; and (4)
eDET on Day 5. Per patient, main analysis included acceptance of assigned group,
as well as multiple and live birth delivery rates of the fresh cycle. Secondary
analysis included the rates of subsequent cryotransfers and the theoretical
cumulative success rate. Of 98 patients selected for eSET, 40% refused and
preferred eDET. The live birth delivery rate after eDET was significantly higher
after eDET versus eSET (65% vs 42%, respectively; odds ratio=1.6, 95% confidence
interval 1.1-2.1). No multiple births were observed after eSET, compared with 35%
after eDET. Although live birth delivery is higher with eDET, the increased risk
of multiple births is avoided with eSET. Nearly half the patients refused eSET
even after having been well informed about its benefits.
PMID- 25128911
TI - Preparing for human papillomavirus vaccine introduction in Kenya: implications
from focus-group and interview discussions with caregivers and opinion leaders in
Western Kenya.
AB - BACKGROUND: Cervical cancer claims the lives of 275,000 women each year; most of
these deaths occur in low-or middle-income countries. In Kenya, cervical cancer
is the leading cause of cancer-related mortality among women of reproductive age.
Kenya's Ministry of Public Health and Sanitation has developed a comprehensive
strategy to prevent cervical cancer, which includes plans for vaccinating preteen
girls against human papillomavirus (HPV) by 2015. To identify HPV vaccine
communication and mobilization needs, this research sought to understand HPV
vaccine-related perceptions and concerns of male and female caregivers and
community leaders in four rural communities of western Kenya. METHODS: We
conducted five focus groups with caregivers (n = 56) and 12 key-informant
interviews with opinion leaders to explore cervical cancer-related knowledge,
attitudes and beliefs, as well as acceptability of HPV vaccination for 9-12 year
old girls. Four researchers independently reviewed the data and developed codes
based on questions in interview guides and topics that emerged organically,
before comparing and reconciling results through a group consensus process.
RESULTS: Cervical cancer was not commonly recognized, though it was understood
generally in terms of its symptoms. By association with cancer and
genital/reproductive organs, cervical cancer was feared and stigmatized. Overall
acceptability of a vaccine that prevents cervical cancer was high, so long as it
was endorsed by trusted agencies and communities were sensitized first. Some
concerns emerged related to vaccine safety (e.g., impact on fertility), program
intent, and health equity. CONCLUSION: For successful vaccine introduction in
Kenya, there is a need for communication and mobilization efforts to raise
cervical cancer awareness; prompt demand for vaccination; address health equity
concerns and stigma; and minimize potential resistance. Visible endorsement by
government leaders and community influencers can provide reassurance of the
vaccine's safety, efficacy and benefits for girls and communities. Involvement of
community leadership, parents and champions may also be critical for combatting
stigma and making cervical cancer relevant to Kenyan communities. These findings
underscore the need for adequate planning and resources for information,
education and communication prior to vaccine introduction. Specific
recommendations for communication and social-marketing strategies are made.
PMID- 25128912
TI - Neurolysis for failed tarsal tunnel surgery.
AB - The purpose of the present study was to investigate the causes of failure after
tarsal tunnel release and the operative findings in the secondary interventions
and the outcomes. The data from 8 patients who had undergone revision surgery for
failed tarsal tunnel release at least 12 months earlier were evaluated
retrospectively. Only the patients with idiopathic tarsal tunnel syndrome were
included, and all had unilateral symptoms. Neurophysiologic tests confirmed the
clinical diagnosis of failed tarsal tunnel release in all patients. Magnetic
resonance imaging revealed varicose veins within the tarsal tunnel in 1 patient
(12.5%) and tenosynovitis in another (12.5%). Open tarsal tunnel release was
performed in all patients, and the tibialis posterior nerve, medial and lateral
plantar nerves (including the first branch of the lateral plantar nerve), and
medial calcaneal nerve were released in their respective tunnels, and the septum
between the tunnels was resected. The outcomes were assessed according to
subjective patient satisfaction as excellent, good, fair, or poor. During
revision surgery, insufficient release of the tarsal tunnel, especially distally,
was observed in all the patients, and fibrosis of the tibialis posterior nerve
was present in 1 (12.5%). The outcomes according to subjective patient
satisfaction were excellent in 5 (62.5%), good in 2 (25%), and fair in 1 (12.5%).
The fair outcome was obtained in the patient with fibrosis of the nerve.
Insufficient release of the tarsal tunnel was the main cause of failed tarsal
tunnel release. Releasing the 4 distinct tunnels and permitting immediate
mobilization provided satisfactory results in patients with failed tarsal tunnel
release.
PMID- 25128913
TI - A minimally invasive "overwrapping" technique for repairing neglected ruptures of
the Achilles tendon.
AB - About 10% to 25% of acute ruptures of the Achilles tendon go undiagnosed for some
time beyond what would be optimal for repair and a return to optimal function.
Managing these chronic or neglected ruptures is a surgical challenge, because the
tendon ends retract and atrophy and could develop a short, fibrous distal stump.
In the present report, a patient with a ruptured right Achilles tendon, neglected
for approximately 10 years, is described. The chronically injured tendon was
successfully treated by overwrapping the interposed scar at the rupture site.
This minimally invasive technique restored tension to the tendon, a prerequisite
for which was the presence of functional triceps surae, confirmed by
identification of gross contraction of the muscle during tiptoeing. The procedure
is contraindicated when the scar tissue is not intact and does not have
sufficient laxity to allow adequate dorsiflexion of the ankle after overwrapping
the tendon or when the triceps surae are nonfunctional.
PMID- 25128914
TI - Use of a flexible implant and bioabsorbable anchor for deltoid rupture repair in
bimalleolar equivalent Weber B ankle fractures.
AB - Supination external rotation ankle fractures are the most common ankle fracture
subtype. Deltoid ligament injuries have often been associated with this type of
injury pattern. A missed injury can lead to post-traumatic arthritis and
persistent pain. The current data do not support acute deltoid rupture repair.
This has been based primarily on level III and IV studies in which less than
satisfactory results were reported. We believe that acute deltoid rupture repair
could be indicated in select cases. We have outlined a new deltoid repair
technique for use with bimalleolar, equivalent supination external rotation ankle
fractures using a flexible implant and bioabsorbable anchor.
PMID- 25128915
TI - Multiple locations of nerve compression: an unusual cause of persistent lower
limb paresthesia.
AB - A paucity of appreciation exists that the "double crush" phenomenon can account
for persistent leg symptoms even after spinal neural decompression surgery. We
present an unusual case of multiple locations of nerve compression causing
persistent lower limb paresthesia in a 40-year old male patient. The patient's
lower limb paresthesia was persistent after an initial spinal surgery to treat
spinal lateral recess stenosis thought to be responsible for the symptoms. It was
later discovered that he had peroneal muscle herniations that had caused
superficial peroneal nerve entrapments at 2 separate locations. The patient
obtained much symptomatic relief after decompression of the peripheral nerve. The
"double crush" phenomenon and multiple levels of nerve compression should be
considered when evaluating lower limb neurogenic symptoms, especially after
spinal nerve root surgery.
PMID- 25128916
TI - Evaluation of cold ischemia for preservation of testicular function during
partial orchiectomy in the rat model.
AB - OBJECTIVE: We hypothesized that cold ischemia during partial orchiectomy would
lead to higher serum testosterone levels and preservation of testicular
architecture than warm ischemia in a prepubescent rat model. MATERIALS AND
METHODS: Eighteen prepubescent male Sprague-Dawley rats were randomized to three
different surgical groups: sham surgery, bilateral partial orchiectomy with 30
min of cord compression with cold ischemia, or bilateral partial orchiectomy with
30 min of cord compression with warm ischemia. Animals were killed at puberty,
and serum, sperm, and testicles were collected. Histological tissue injury was
graded by standardized methodology. RESULTS: Mean serum testosterone levels were
1445 +/- 590 pg/mL for the sham group, 449 +/- 268 pg/mL for the cold ischemia
group and 879 +/- 631 pg/mL for the warm ischemia group (p = 0.12). Mean sperm
counts were 2.1 * 10(7) for sham, 4.4 * 10(6) for cold ischemia, and 9.9 * 10(6)
for the warm ischemia groups (p = 0.48). Histological evaluation revealed
significant difference in tissue injury grading with more injury in the cold
ischemia than in the warm ischemia group (p = 0.01). CONCLUSIONS: In our
preclinical rat model, we found no benefit for cold ischemia over warm ischemia
at 30 min.
PMID- 25128917
TI - Conversion of calcium sulphide to calcium carbonate during the process of
recovery of elemental sulphur from gypsum waste.
AB - The production of elemental sulphur and calcium carbonate (CaCO3) from gypsum
waste can be achieved by thermally reducing the waste into calcium sulphide
(CaS), which is then subjected to a direct aqueous carbonation step for the
generation of hydrogen sulphide (H2S) and CaCO3. H2S can subsequently be
converted to elemental sulphur via the commercially available chemical catalytic
Claus process. This study investigated the carbonation of CaS by examining both
the solution chemistry of the process and the properties of the formed carbonated
product. CaS was successfully converted into CaCO3; however, the reaction yielded
low-grade carbonate products (i.e. <90 mass% as CaCO3) which comprised a mixture
of two CaCO3 polymorphs (calcite and vaterite), as well as trace minerals
originating from the starting material. These products could replace the Sappi
Enstra CaCO3 (69 mass% CaCO3), a by-product from the paper industry which is used
in many full-scale AMD neutralisation plants but is becoming insufficient. The
insight gained is now also being used to develop and optimize an indirect aqueous
CaS carbonation process for the production of high-grade CaCO3 (i.e. >99 mass% as
CaCO3) or precipitated calcium carbonate (PCC).
PMID- 25128918
TI - Heavy metal and nutrient changes during vermicomposting animal manure spiked with
mushroom residues.
AB - A pilot-scale trial of four months was conducted to investigate the responses of
heavy metal and nutrient to composting animal manure spiked with mushroom
residues with and without earthworms. Results showed that earthworm activities
accelerated organic matter mineralization (e.g. reduction in C/N ratio, increase
in total concentrations of N, P, K) and humification (e.g. increase in humic acid
concentration, humification ratio and humification index). Despite composting
increased total heavy metal (i.e. As, Pb, Cu, Zn) concentrations irrespective of
earthworm, the availability of heavy metals extracted by DTPA significantly
(P<0.05) decreased particularly in treatments with earthworms introduced. The
shift from available to unavailable fractions of heavy metals was either due to
earthworm bioaccumulation, as indicated by total heavy metal concentrations being
higher in earthworm tissues, or due to the formation of stable metal-humus
complexes as indicated by the promotion of humification. Our results suggest that
vermicomposting process could magnify the nutrient quality but relieve the heavy
metals risk of agricultural organic wastes.
PMID- 25128920
TI - A lower content of de-methylesterified homogalacturonan improves enzymatic cell
separation and isolation of mesophyll protoplasts in Arabidopsis.
AB - Cell adhesion occurs primarily at the level of middle lamella which is mainly
composed by pectin polysaccharides. These can be degraded by cell wall degrading
enzymes (CWDEs) during developmental processes to allow a controlled separation
of plant cells. Extensive cell wall degradation by CWDEs with consequent cell
separation is performed when protoplasts are isolated from plant tissues by using
mixtures of CWDEs. We have evaluated whether modification of pectin affects cell
separation and protoplast isolation. Arabidopsis plants overexpressing the pectin
methylesterase inhibitors AtPMEI-1 or AtPMEI-2, and Arabidopsis pme3 plants,
mutated in the gene encoding pectin methylesterase 3, showed an increased
efficiency of isolation of viable mesophyll protoplasts as compared with Wild
Type Columbia-0 plants. The release of protoplasts was correlated with the
reduced level of long stretches of de-methylesterified homogalacturonan (HGA)
present in these plants. Response to elicitation, cell wall regeneration and
efficiency of transfection in protoplasts from transgenic plants was comparable
to those of wild type protoplasts.
PMID- 25128921
TI - Identifying primary Sjogren syndrome in children: case report.
AB - Primary Sjogren syndrome (PSS) rarely occurs in children. In addition, because
the objective and subjective diagnostic criteria for juvenile PSS differ from
those seen in adults, identification of its presence can be difficult to
establish. This case report illustrates the accepted benchmarks for diagnosing
pediatric PSS.
PMID- 25128919
TI - Determinants of methicillin-susceptible Staphylococcus aureus native bone and
joint infection treatment failure: a retrospective cohort study.
AB - BACKGROUND: Although methicillin-susceptible Staphylococcus aureus (MSSA) native
bone and joint infection (BJI) constitutes the more frequent clinical entity of
BJI, prognostic studies mostly focused on methicillin-resistant S. aureus
prosthetic joint infection. We aimed to assess the determinants of native MSSA
BJI outcomes. METHODS: Retrospective cohort study (2001-2011) of patients
admitted in a reference hospital centre for native MSSA BJI. Treatment failure
determinants were assessed using Kaplan-Meier curves and binary logistic
regression. RESULTS: Sixty-six patients (42 males [63.6%]; median age 61.2 years;
interquartile range [IQR] 45.9-71.9) presented an acute (n = 38; 57.6%) or
chronic (n = 28; 42.4%) native MSSA arthritis (n = 15; 22.7%), osteomyelitis (n =
19; 28.8%) or spondylodiscitis (n = 32; 48.5%), considered as "difficult-to
treat" in 61 cases (92.4%). All received a prolonged (27.1 weeks; IQR, 16.9-36.1)
combined antimicrobial therapy, after surgical management in 37 cases (56.1%).
Sixteen treatment failures (24.2%) were observed during a median follow-up period
of 63.3 weeks (IQR, 44.7-103.1), including 13 persisting infections, 1 relapse
after treatment disruption, and 2 super-infections. Independent determinants of
treatment failure were the existence of a sinus tract (odds ratio [OR], 5.300;
95% confidence interval [CI], 1.166-24.103) and a prolonged delay to infectious
disease specialist referral (OR, 1.134; 95% CI 1.013-1.271). CONCLUSIONS: The
important treatment failure rate pinpointed the difficulty of cure encountered in
complicated native MSSA BJI. An early infectious disease specialist referral is
essential, especially in debilitated patients or in presence of sinus tract.
PMID- 25128922
TI - Does alveolar corticotomy accelerate orthodontic tooth movement when retracting
upper canines? A split-mouth design randomized controlled trial.
AB - PURPOSE: To evaluate the efficacy of alveolar corticotomy on orthodontic tooth
movement when retracting upper canines compared with the conventional technique
and to evaluate patients' pain and discomfort levels after corticotomy. MATERIALS
AND METHODS: A split-mouth design randomized controlled trial at the Department
of Orthodontics (University Al-Baath Dental School) was performed. A total of 30
patients whose orthodontic treatment required canine retraction were included.
The predictor variable was the use of corticotomy to facilitate tooth movement.
The velocity of space closure was evaluated as the primary outcome variable by
measuring the distance between the canine and first molar on each side of the
mouth immediately after corticotomy and at 1, 2, 4, 8, and 12 weeks after
corticotomy. The levels of pain and discomfort were evaluated as the secondary
outcome variables using a questionnaire administered 4 times during the first
week after corticotomy. Paired t tests or Wilcoxon matched-pairs signed-rank
tests were used to detect significant differences. RESULTS: A total of 30
patients (15 males and 15 females) were recruited with a mean age of 20.04 +/-
3.63 years (range 15 to 24). The space closure velocity after corticotomy was
significantly faster on the experimental side than on the control side (mean =
0.74 mm/week vs 0.20 mm/week between 1 week after and immediately after
corticotomy, respectively; P < .001). The pain encountered during eating was
high, with 50% and 30% of patients reporting severe pain at 1 and 3 days
postoperatively, respectively. No significant differences were detected between
the male and female patients regarding the tooth movement velocity on the
experimental side. CONCLUSIONS: Alveolar corticotomy increased orthodontic tooth
movement and was accompanied by moderate degrees of pain and discomfort.
PMID- 25128923
TI - Sleeve gastrectomy and mesenteric venous thrombosis: report of 3 patients and
review of the literature.
PMID- 25128924
TI - Bipolar impedance-controlled sealing of the pulmonary artery with SealSafe G3
electric current: determination of bursting pressures in an ex vivo model.
AB - BACKGROUND: In every anatomic lung resection operation, the pulmonary artery
itself or its branches must be sealed. This involves either stapling or ligating
the vessels. Based on the positive results with the bipolar vessel sealing <=7 mm
in abdominal surgery the present study aimed to evaluate burst pressures of the
pulmonary artery after sealing with the sealing instrument SealSafe G3 (Gebruder
Martin & CoKG, Tuttlingen, Germany). MATERIAL AND METHODS: The whole pulmonary
artery above the pulmonary valve was exposed up to the periphery of the left lung
in freshly removed pig heart-lung blocks. A pressure-measuring cylinder was then
implanted in the prepared vessel on the side at the main trunk of the pulmonary
artery to determine the pressure in the vessel. After either ligation or bipolar
sealing of the pulmonary artery, the pneumatic burst pressure (millimeters of
mercury) was determined in a water bath. Three groups (n = 12 for each seal type)
with different vessel diameters were examined: group 1: 0-6 mm, group 2: 7-12 mm,
and group 3: >12 mm. In all cases, vessel sealing was performed with a MARSEAL 5
instrument (Gebruder Martin & Co KG, Tuttlingen, Germany) and the SealSafe G3
current. The mean burst pressures of the individual groups (ligature and bipolar
sealing) were compared using two-tailed, nonparametric Mann-Whitney U test.
Significance was defined as P < 0.05. RESULTS: The mean burst pressures in group
1 were measured by 340 +/- 13.4 mm Hg with ligature and 205 +/- 44.4 mm Hg with
bipolar sealing (P < 0.001). In group 2, the mean values obtained were 270 +/-
28.2 mm Hg for ligature and 162 +/- 36.0 mm Hg for bipolar sealing (P < 0.001).
In group 3, the mean burst pressures for bipolar sealing were only 52.1 +/- 15.1
mm Hg, whereas those for ligated vessels were 253 +/- 46.9 mm Hg (P < 0.001). For
this size of vessel the burst pressure was also determined after stapling. The
mean value in this case was 230 +/- 21.8 mm Hg. CONCLUSIONS: In all groups, the
mean burst pressures after bipolar sealing were significantly lower than those
achieved with ligation, but they were sufficient for a save closure of the
pulmonary artery with diameters up to 12 mm.
PMID- 25128925
TI - Impact of occult hepatitis B virus infection on outcome after resection for non-B
non-C hepatocellular carcinoma.
AB - BACKGROUND: To investigate the clinicopathologic characteristics of patients with
both hepatitis B virus-surface antigen and hepatitis C virus antibody negative
hepatocellular carcinoma (non-B non-C HCC [NBNC-HCC]) and examine the impact of
occult hepatitis B virus infection (OBI) on patients' survival. METHODS: All
patients with OBI were identified from a database of patients with NBNC-HCC who
underwent surgical resection between January 1, 2006, and December 31, 2008.
Their clinicopathologic and survival characteristics were compared with NBNC-HCC
patients without OBI. RESULTS: Out of the 86 NBNC-HCC patients, 59 patients
(68.6%) with OBI. A higher prevalence of hepatitis B core antigen positive rate,
low platelet count, portal hypertension, and liver cirrhosis were observed in
NBNC-HCC patients with OBI. The 1- and 3-y recurrence free survival rates were
66% and 25% in OBI group and 89% and 70% in the no OBI group, respectively (P <
0.001). The 1-, 3-, and 5-y overall survival rates were 86%, 55%, and 51% in OBI
group and 93%, 85%, and 66% in no OBI group, respectively (P = 0.112).
Multivariate analysis revealed that OBI (hazard ratio [HR] = 2.122; 95%
confidence interval [CI], 1.086-4.149; P = 0.028), liver cirrhosis (HR = 2.411;
95% CI, 1.337-4.345; P = 0.003), and vascular invasion (HR = 5.858; 95% CI, 2.799
12.261; P < 0.001) were independent poor prognostic factors for recurrence free
survival of patients with NBNC-HCC. CONCLUSIONS: NBNC-HCC patients with OBI had a
poorer prognosis. OBI can be a useful predictor for recurrence in patients with
NBNC-HCC after surgery.
PMID- 25128926
TI - Comparative metabolic flux analysis of an Ashbya gossypii wild type strain and a
high riboflavin-producing mutant strain.
AB - In the present study, we analyzed the central metabolic pathway of an Ashbya
gossypii wild type strain and a riboflavin over-producing mutant strain developed
in a previous study in order to characterize the riboflavin over-production
pathway. (13)C-Metabolic flux analysis ((13)C-MFA) was carried out in both
strains, and the resulting data were fit to a steady-state flux isotopomer model
using OpenFLUX. Flux to pentose-5-phosphate (P5P) via the pentose phosphate
pathway (PPP) was 9% higher in the mutant strain compared to the wild type
strain. The flux from purine synthesis to riboflavin in the mutant strain was
1.6%, while that of the wild type strain was only 0.1%, a 16-fold difference. In
addition, the flux from the cytoplasmic pyruvate pool to the extracellular
metabolites, pyruvate, lactate, and alanine, was 2-fold higher in the mutant
strain compared to the wild type strain. This result demonstrates that increased
guanosine triphosphate (GTP) flux through the PPP and purine synthesis pathway
(PSP) increased riboflavin production in the mutant strain. The present study
provides the first insight into metabolic flux through the central carbon pathway
in A. gossypii and sets the foundation for development of a quantitative and
functional model of the A. gossypii metabolic network.
PMID- 25128927
TI - Role of vitamin C and selenium in attenuation of nicotine induced oxidative
stress, P53 and Bcl2 expression in adult rat spleen.
AB - Forty adult female rats were randomly divided into four groups: control,
nicotine, nicotine+vitamin C and nicotine+selenium group. Splenic tissues
concentrations of thiobarbituric acid reactive substances (TBARS), nitric oxide,
superoxide dismutase (SOD) and catalase (CAT) activities were measured. The P53
and Bcl2 proteins were detected by Western blot and their expression in splenic
tissues were measured by quantitative real time PCR in all groups. Compared to
control group, nicotine increased the concentrations of TBARS and nitric oxide
significantly. However, Vit. C or Se supplementation with nicotine caused a
significant decrease in these concentrations. SOD and CAT activities of nicotine
group decreased significantly compared to control group. Treatment with Vit. C or
Se plays a significant role in elevation of SOD and CAT activities. In splenic
tissues, nicotine significantly decreases the protein levels and the mRNA
expression of P53 and increases the protein levels of Bcl2 and its expression.
Administration of Vit. C. to nicotine-treated rats completely reversed the
decrease in P53 levels and its mRNA expression and the increase in Bcl2 levels
and its mRNA expression to the control values. In contrast, Se administration did
not induce any significant changes in these genes levels or expressions compared
to nicotine group. CONCLUSION: Vit. C supplementation to nicotine treated rats
was more effective than selenium in attenuation of nicotine-induced oxidative
stress, p53 and Bcl2 expression in rat spleen tissues.
PMID- 25128928
TI - A systematic review of the effect of daily panty liner use on the vulvovaginal
environment.
AB - BACKGROUND: Whether panty liners predispose to vulvovaginitis is unclear.
OBJECTIVES: To clarify the effects of the use of panty liners on the female
genital tract. SEARCH STRATEGY: Several electronic databases (including PubMed
and Embase) were searched to identify studies published in English before May 3,
2012. SELECTION CRITERIA: Case-control studies, randomized controlled trials, and
cohort studies comparing young women who did and did not use panty liners in the
intermenstrual period were included. DATA COLLECTION AND ANALYSIS: The quality of
the studies was assessed using the Newcastle-Ottawa Scale or the Jadad Scale.
Data from suitable studies were extracted for analysis. MAIN RESULTS: Five
articles met the inclusion criteria. Four studies-all of which included only
healthy women-found no significant clinical implications arising from the use of
panty liners. The fifth study was of women with recurrent candidiasis and showed
that use of panty liners was associated with new candidiasis episodes.
CONCLUSIONS: The intermenstrual use of panty liners does not seem to have a
negative effect on the vulvovaginal area.
PMID- 25128929
TI - Pilot community-mobilization program reduces maternal and perinatal mortality and
prevents obstetric fistula in Niger.
AB - OBJECTIVE: To assess the impact of a pilot community-mobilization program on
maternal and perinatal mortality and obstetric fistula in Niger. METHODS: In the
program, village volunteers identify and evacuate women with protracted labor,
provide education, and collect data on pregnancies, births, and deaths. These
data were used to calculate the reduction in maternal mortality, perinatal
mortality, and obstetric fistula in the program area from July 2008 to June 2011.
RESULTS: The birth-related maternal mortality fell by 73.0% between years 1 and 3
(P<0.001), from 630 (95% confidence interval [CI] 448-861) to 170 (95% CI 85-305)
deaths per 100 000 births. Early perinatal mortality fell by 61.5% (P<0.001),
from 35 (95% CI 31-40) to 13 (95% CI 10-16) deaths per 1000 births. No deaths due
to obstructed labor were reported after the lead-in period (February to June
2008). Seven cases of community-acquired fistula were reported between February
2008 and July 2009; from August 2009 to June 2011 (23 months; 12 254 births), no
cases were recorded. CONCLUSION: Community mobilization helped to prevent
obstetric fistula and birth-related deaths of women and infants in a large,
remote, resource-poor area.
PMID- 25128930
TI - Emerging lessons from the FIGO LOGIC initiative on maternal death and near-miss
reviews.
AB - This short paper describes some early findings from an overview of the maternal
death or severe morbidity "near-miss" reviews that have been undertaken to
improve clinical care by the eight societies participating in the FIGO Leadership
in Obstetrics and Gynecology for Impact and Change (LOGIC) Initiative in Maternal
and Newborn Health aimed at strengthening the role of professional obstetric
associations. While it is expected that each will publish its own report,
generalizable lessons emerged and valuable solutions were implemented that will
help others planning such reviews and audits in future.
PMID- 25128931
TI - Norepinephrine infusion with and without alpha-adrenergic blockade by
phentolamine increases salivary alpha amylase in healthy men.
AB - BACKGROUND: Mental stress reliably induces increases in salivary alpha amylase
(sAA), a suggested surrogate marker for sympathetic nervous system (SNS)
reactivity. While stress-induced sAA increases correlate with norepinephrine (NE)
secretion, a potential mediating role of noradrenergic mechanisms remains
unclear. In this study, we investigated for the first time in humans whether a NE
stress-reactivity mimicking NE-infusion with and without alpha-adrenergic
blockade by phentolamine would induce changes in sAA. METHODS: In a single-blind
placebo-controlled within-subjects design, 21 healthy men (29-66 years) took part
in three different experimental trials varying in terms of substance infusion
with a 1-min first infusion followed by a 15-min second infusion: saline-infusion
(trial-1), NE-infusion (5 MUg/min) without alpha-adrenergic blockade (trial-2),
and with phentolamine-induced non-selective blockade of alpha1- and alpha2
adrenergic receptors (trial-3). Saliva samples were collected immediately before,
during, and several times after substance infusion in addition to blood pressure
and heart rate readings. RESULTS: Experimental trials significantly differed in
sAA reactivity to substance-infusion (p=.001) with higher sAA reactivity
following NE-infusion with (trial-3; p=.001) and without alpha-adrenergic
blockade (trial-2; p=.004) as compared to placebo-infusion (trial-1); sAA
infusion reactivity did not differ between trial-2 and trial-3 (p=.29). Effective
phentolamine application was verified by blood pressure and heart rate infusion
reactivity. Salivary cortisol was not affected by NE, either with or without
alpha-adrenergic-blockade. CONCLUSIONS: We found that NE-infusion stimulates sAA
secretion, regardless of co-administered non-selective alpha-adrenergic blockade
by phentolamine, suggesting that the mechanism underlying stress-induced sAA
increases may involve NE.
PMID- 25128932
TI - A new Brucella canis species-specific PCR assay for the diagnosis of canine
brucellosis.
AB - Brucellosis is a zoonotic disease that is transmitted from animals to humans, and
the development of a rapid, accurate, and widely available identification method
is essential for diagnosing this disease. In this study, we developed a new
Brucella canis species-specific (BcSS) PCR assay and evaluated its specificity
and sensitivity. A specific PCR primer set was designed based on the BCAN_B0548
0549 region in chromosome II of B. canis. The PCR detection for B. canis included
amplification of a 300-bp product that is, not found on other Brucella species
or, genetically or serologically related bacteria. The detection limit of BcSS
PCR assay was 6pg/MUl by DNA dilution, or 3*10(3) colony-forming units (CFU) in
the buffy coats separated from whole blood experimentally inoculated with B.
canis. Using the buffy coat in this PCR assay resulted in approximately 100-times
higher sensitivity for B. canis as compared to detect directly from whole blood.
This is the first report of a species-specific PCR assay to detect B. canis, and
the new assay will provide a valuable tool for the diagnosis of B. canis
infection.
PMID- 25128933
TI - Repair of a radial tear in the posterior horn of the lateral meniscus.
AB - BACKGROUND: There have been no studies evaluating the clinical results after
repair of a radial tear in the posterior horn of the lateral meniscus (PHLM)
using the FasT-Fix system. This study was undertaken to evaluate the clinical
outcomes after repair of a radial tear in the PHLM using the FasT-Fix system in
conjunction with anterior cruciate ligament (ACL) reconstruction. METHODS:
Between September 2008 and August 2011, 15 radial tears in the PHLM identified
during 132 consecutive ACL reconstructions were repaired using the FasT-Fix
meniscal repair system. We classified the radial tears into three types according
to the tear patterns: simple radial tear, complex radial tear, and radial tear
involving the popliteal hiatus. Postoperative evaluation was performed using the
Lysholm knee score and Tegner activity level. Second-look arthroscopy was
performed in all cases. RESULTS: The mean follow-up period was 24 months. None of
the patients had a history of recurrent effusion, joint line tenderness or a
positive McMurray test. The meniscal repair was considered to have a 100%
clinical success rate. At the final follow-up, the Lysholm knee score and Tegner
activity level were significantly improved compared to the preoperative values.
On the second-look arthroscopy, repair of radial tears in the PHLM in conjunction
with ACL reconstruction using the FasT-Fix device resulted in complete or partial
healing in 86.6% of cases. CONCLUSION: Clinical results after meniscal repair of
a radial tear in the PHLM by using the FasT-Fix system were satisfactory. LEVEL
OF EVIDENCE: Case series, Level IV.
PMID- 25128935
TI - Renal denervation in hypertension: simplicity, or complexity?
PMID- 25128934
TI - Management of outpatients in France with stable coronary artery disease. Findings
from the prospeCtive observational LongitudinAl RegIstry oF patients with stable
coronary arterY disease (CLARIFY) registry.
AB - BACKGROUND: Improvements in the treatment of coronary artery disease mean that an
increasing number of patients survive acute cardiovascular events and live as
outpatients with or without anginal symptoms. AIM: To determine the
characteristics and management of contemporary outpatients with stable coronary
artery disease in Western Europe, and to compare France with the other Western
European countries. METHODS: CLARIFY (prospeCtive observational LongitudinAl
RegIstry oF patients with stable coronary arterY disease) is an international,
prospective, observational, longitudinal study. Between November 2009 and July
2010, 32,954 adult outpatients with stable coronary artery disease (defined as a
history of documented myocardial infarction [of >3 months], prior coronary
revascularization, chest pain with myocardial ischaemia, or coronary stenosis
of>50% proven by angiography) were enrolled in 45 countries. The demographics and
management of CLARIFY patients enrolled in France were compared with those
enrolled in other Western European countries (Austria, Belgium, Denmark, Germany,
Greece, Ireland, Italy, Netherlands, Portugal, Spain, Switzerland and the UK).
RESULTS: Of the 14,726 patients enrolled in Western Europe (mean age 66.2 [10.2]
years; 79.6% male), 2432 (16.5%) were from France. The use of aspirin was lower
in France than in other Western European countries (74.5% vs. 86.9%,
respectively), whereas use of thienopyridines (48.5% vs. 21.7%), oral
anticoagulants (12.3% vs. 9.0%) and lipid-lowering drugs (95.8% vs. 92.5%) was
higher. Beta-blockers were used in 73% of both groups. Angina was less prevalent
in France (6.3% vs. 15.5%) and French patients showed higher levels of physical
activity than their counterparts in Western Europe. CONCLUSIONS: The management
of patients with stable CAD in France appears favourable, with good adherence to
guideline-based therapies, but there remains room for improvement in terms of
symptom and risk factor control.
PMID- 25128937
TI - Close to the heart.
PMID- 25128938
TI - The promise of high-sensitivity troponin testing.
PMID- 25128939
TI - Data needs in child maltreatment response.
PMID- 25128940
TI - Ocular biomarkers for neurodegenerative and systemic disease.
PMID- 25128942
TI - AIDS, loss and renewal.
PMID- 25128943
TI - Problem-based learning in medical education: one of many learning paradigms.
PMID- 25128944
TI - Excessive occupational sitting is not a "safe system of work": time for doctors
to get chatting with patients.
PMID- 25128945
TI - Role of the medical community in detecting and managing child abuse.
PMID- 25128946
TI - Removing the interview for medical school selection is associated with gender
bias among enrolled students.
PMID- 25128947
TI - Removing the interview for medical school selection is associated with gender
bias among enrolled students.
PMID- 25128949
TI - Cardiopulmonary resuscitation--time for a change in the paradigm?
AB - Cardiopulmonary resuscitation (CPR) is the default treatment in hospital unless
there is a decision to the contrary and this is documented in the patient record.
The outcome of CPR in older chronically ill patients is very poor and discharge
home is unlikely. Fewer not-for-resuscitation (NFR) orders are written than there
are patients who would not benefit from CPR. NFR orders appear to be a marker of
death, rather than the result of informed discussion about end-of-life care.
There is a legal and ethical framework for the consideration of the suitability
of CPR. Discussions about CPR are challenging, and uncertainty is introduced
because of the lack of consensus around futility, the emotionally charged nature
of the topic, misconceptions about the success of CPR and the failure to
recognise that not offering CPR will allow a peaceful and supported death.
Discussion around CPR can be misconstrued as a need for consent. A focus on
patient and family involvement may result in an expectation that CPR is an
entitlement. As part of evidence-based patient-centred care, CPR should only be
offered to those for whom it is beneficial. CPR should no longer be the universal
default. We propose an opt-in model, which will drive discussion and evaluation
of the efficacy and suitability of CPR for the individual. A CPR discussion
should occur on admission for all elderly hospital inpatients.
PMID- 25128948
TI - A systematic approach to chronic heart failure care: a consensus statement.
AB - The National Heart Foundation of Australia assembled an expert panel to provide
guidance on policy and system changes to improve the quality of care for people
with chronic heart failure (CHF). The recommendations have the potential to
reduce emergency presentations, hospitalisations and premature death among
patients with CHF. Best-practice management of CHF involves evidence-based,
multidisciplinary, patient-centred care, which leads to better health outcomes. A
CHF care model is required to achieve this. Although CHF management programs
exist, ensuring access for everyone remains a challenge. This is particularly so
for Aboriginal and Torres Strait Islander peoples, those from non-metropolitan
areas and lower socioeconomic backgrounds, and culturally and linguistically
diverse populations. Lack of data and inadequate identification of people with
CHF prevents efficient patient monitoring, limiting information to improve or
optimise care. This leads to ineffectiveness in measuring outcomes and evaluating
the CHF care provided. Expanding current cardiac registries to include patients
with CHF and developing mechanisms to promote data linkage across care
transitions are essential. As the prevalence of CHF rises, the demand for
multidisciplinary workforce support will increase. Workforce planning should
provide access to services outside of large cities, one of the main challenges it
is currently facing. To enhance community-based management of CHF, general
practitioners should be empowered to lead care. Incentive arrangements should
favour provision of care for Aboriginal and Torres Strait Islander peoples, those
from lower socioeconomic backgrounds and rural areas, and culturally and
linguistically diverse populations. Ongoing research is vital to improving
systems of care for people with CHF. Future research activity needs to ensure the
translation of valuable knowledge and high-quality evidence into practice.
PMID- 25128950
TI - Should general practitioners order troponin tests?
AB - Cardiac troponin I and T are the preferred biomarkers for assessing myocardial
injury, and the timing of troponin testing is fundamental to its clinical
utility. There are arguments for and against the use of troponin testing in the
community, and the stance that general practitioners should never order a
troponin test can be considered an oversimplification. GPs have a generally
sufficient understanding of the test for use in primary care, and have a better
understanding of false-negative troponin test results than false-positive
results. We suggest that hospitalisation, rather than troponin testing, should be
the default option for patients with symptoms suggestive of acute coronary
syndrome. A single troponin test is reasonable in primary care to exclude the
possibility of acute myocardial infarction in asymptomatic low-risk patients
whose symptoms resolved at least 12 hours prior. GPs should factor in the complex
logistics of troponin testing in the community before ordering a troponin test:
results need to be accurate and timely, and might be obtained at a time of day
when it is difficult to contact the doctor or the patient.
PMID- 25128951
TI - Impact of high-sensitivity cardiac troponin I assays on patients presenting to an
emergency department with suspected acute coronary syndrome.
AB - OBJECTIVE: To determine whether introduction of high-sensitivity cardiac troponin
I (hscTn-I) assays affected management of patients presenting with suspected
acute coronary syndrome (ACS) to the emergency department (ED) of a tertiary
referral hospital. DESIGN, PATIENTS AND SETTING: A retrospective analysis of all
patients presenting to the Geelong Hospital ED with suspected ACS from 23 April
2010 to 22 April 2013 -2 years before and 1 year after the changeover to hscTn-I
assays on 23 April 2012. MAIN OUTCOME MEASURES: Hospital admission rates, time
spent in the ED, rates of coronary angiography, rates of percutaneous coronary
intervention (PCI) and coronary artery bypass graft surgery (CABGS), rates of
discharge with a diagnosis of ACS, and rates of inhospital mortality. RESULTS: 12
360 consecutive patients presented with suspected ACS during the study period;
1897 were admitted to Geelong Hospital in the 2 years before and 944 in the 1
year after the changeover to hscTn-I assays. Comparing the two patient groups,
there was no statistically significant difference in all-hospital admission rates
(95% CI for the difference, - 3.1% to 0.3%; P = 0.10) or proportion of patients
subsequently discharged with a diagnosis of ACS (95% CI for the difference, -
2.3% to 5.4%; P = 0.43). After the changeover, the median time patients spent in
the ED was 11.5% shorter (3.85 h v 4.35 h; 95% CI for the difference, - 0.59 to -
0.43; P < 0.001) and the proportion of admitted patients undergoing coronary
angiography was higher (53.4% v 45.2%; 95% CI for the difference, 4.3 to 12.0
percentage points; P < 0.001), but there was no statistically significant rise in
the proportion of patients who had invasive treatment (PCI and/or CABGS) (95% CI
for the difference, - 0.4% to 6.3%; P = 0.08). Inhospital mortality rates from
ACS did not change significantly (95% CI for the difference, - 1.5% to 0.8%; P =
0.43). CONCLUSION: The introduction of hscTn-I assays appeared to be associated
with more rapid diagnosis, resulting in less time spent in the ED, without a
change in hospital admission rates. A higher proportion of patients had coronary
angiographies after the changeover, but there was no significant change in rates
of invasive treatment or inhospital mortality.
PMID- 25128952
TI - Trends in hospital admissions for conditions associated with child maltreatment,
Northern Territory, 1999-2010.
AB - OBJECTIVE: To use hospital admissions data to investigate trends in maltreatment
among Northern Territory Aboriginal and non-Aboriginal children. DESIGN, SETTING
AND PARTICIPANTS: A historical cohort study using diagnosis and external cause
codes from hospital admissions among children aged 0-17 years. MAIN OUTCOME
MEASURES: Annual rates of admission with either a definitive or indicative code
for child maltreatment. RESULTS: From 1 January 1999 to 31 December 2010, the
average annual rates of hospital admission of NT Aboriginal and non-Aboriginal
children with a definitive code of maltreatment were 8.8 (95% CI, 7.4-10.2) and
0.91 (95% CI, 0.59-1.22) per 10 000 children, respectively. There was no evidence
for change over time in either population. The corresponding rates of admission
with a code indicative of maltreatment were 28.4 (95% CI, 25.8-31.1) and 5.2 (95%
CI, 4.4-6.0) per 10 000 children, with average annual increases of 3% (incidence
rate ratio [IRR], 1.03; 95% CI, 1.00-1.07) and 4% (IRR, 1.04; 95% CI, 0.96-1.11).
Physical abuse was the prominent type of maltreatment-related admission in both
populations. There were increases in rates of admission for older Aboriginal
children (13-17 years) and older non-Aboriginal boys. Most perpetrators in the
assault of younger children were family members, while among older children most
were not specified. CONCLUSION: Our study shows the utility of hospital
admissions for population surveillance of child maltreatment. The relatively
stable rate of maltreatment-related hospital admissions among NT Aboriginal
children shown here is in contrast to substantial increases reported from child
protection data. The results also highlight the overlap between violence within
families and in the wider community, particularly for older children, and lends
support for population-level interventions to protect vulnerable children.
PMID- 25128954
TI - All that is irregular is not AF!
PMID- 25128953
TI - Cardiopulmonary arrest and mortality trends, and their association with rapid
response system expansion.
AB - OBJECTIVES: To understand the changes in the population incidence of inhospital
cardiopulmonary arrest (IHCA) and mortality associated with the introduction of
rapid response systems (RRSs). DESIGN, SETTING AND PARTICIPANTS: Population-based
study of 9 221 138 hospital admissions in 82 public acute hospitals in New South
Wales, using data linked to a death registry, from 1 Jan 2002 to 31 Dec 2009.
MAIN OUTCOME MEASURES: Changes in IHCA, IHCA-related mortality, hospital
mortality and proportion of IHCA patients surviving to hospital discharge.
RESULTS: RRS uptake increased from 32% in 2002 to 74% in 2009. This increase was
associated with a 52% decrease in IHCA rate, a 55% decrease in IHCA-related
mortality rate, a 23% decrease in hospital mortality rate and a 15% increase in
survival to discharge after an IHCA (all P < 0.01). The adjusted absolute
reductions in IHCA-related mortality and hospital mortality were 1.49 (95% CI,
1.30-1.68) and 4.05 (95% CI, 3.17-4.76) patients per 1000 admissions,
respectively. The decrease in IHCA incidence rate accounted for 95% of the
reduction in IHCA-related mortality. In contrast, the increase in IHCA survival
accounted for only 5% of the reduction in IHCA-related mortality. CONCLUSIONS:
During nearly a decade, as RRSs were progressively introduced, there was a
coincidental reduction in IHCA, IHCA-related deaths and hospital mortality and an
increased survival to hospital discharge after an IHCA. Reduced IHCA incidence,
rather than improved postcardiac arrest survival, was the main contributor to the
reduction in IHCA mortality.
PMID- 25128955
TI - Health care--the secular Leviathan.
PMID- 25128958
TI - Targeting death receptors for TRAIL by agents designed by Mother Nature.
AB - Selective killing of cancer cells is one of the major goals of cancer therapy.
Although chemotherapeutic agents are being used for cancer treatment, they lack
selectivity toward tumor cells. Among the six different death receptors (DRs)
identified to date, DR4 and DR5 are selectively expressed on cancer cells.
Therefore, unlike chemotherapeutic agents, these receptors can potentially
mediate selective killing of tumor cells. In this review we outline various
nutraceuticals derived from 'Mother Nature' that can upregulate DRs and thus
potentiate apoptosis. These nutraceuticals increase tumor necrosis factor (TNF)
related apoptosis-inducing ligand (TRAIL)-induced apoptosis of cancer cells
through different mechanisms. First, nutraceuticals have been found to induce DRs
through the upregulation of various signaling molecules. Second, nutraceuticals
can downregulate tumor cell-survival pathways. Third, nutraceuticals alone have
been found to activate cell-death pathways. Although both TRAIL and agonistic
antibodies against DR4 and DR5 are in clinical trials, combination with
nutraceuticals is likely to boost their anticancer potential.
PMID- 25128959
TI - Comprehensive evaluation of PCA-based finite element modelling of the human
femur.
AB - Computed tomography (CT)-based finite element (FE) reconstructions describe shape
and density distribution of bones. Both shape and density distribution, however,
can vary a lot between individuals. Shape/density indexation (usually achieved by
principal component analysis--PCA) can be used to synthesize realistic models,
thus overcoming the shortage of CT-based models, and helping e.g. to study
fracture determinants, or steer prostheses design. The aim of this study was to
describe a PCA-based statistical modelling algorithm, and test it on a large CT
based population of femora, to see if it can accurately describe and reproduce
bone shape, density distribution, and biomechanics. To this aim, 115 CT-datasets
showing normal femoral anatomy were collected and characterized. Isotopological
FE meshes were built. Shape and density indexation procedures were performed on
the mesh database. The completeness of the database was evaluated through a
convergence study. The accuracy in reconstructing bones not belonging to the
indexation database was evaluated through (i) leave-one-out tests (ii) comparison
of calculated vs. in-vitro measured strains. Fifty indexation modes for shape and
40 for density were necessary to achieve reconstruction errors below pixel size
for shape, and below 10% for density. Similar errors for density, and slightly
higher errors for shape were obtained when reconstructing bones not belonging to
the database. The in-vitro strain prediction accuracy of the reconstructed FE
models was comparable to state-of-the-art studies. In summary, the results
indicate that the proposed statistical modelling tools are able to accurately
describe a population of femora through finite element models.
PMID- 25128957
TI - Respondent driven sampling is an effective method for engaging methamphetamine
users in HIV prevention research in South Africa.
AB - BACKGROUND: South Africa, in the midst of the world's largest HIV epidemic, has a
growing methamphetamine problem. Respondent driven sampling (RDS) is a useful
tool for recruiting hard-to-reach populations in HIV prevention research, but its
use with methamphetamine smokers in South Africa has not been described. This
study examined the effectiveness of RDS as a method for engaging methamphetamine
users in a Cape Town township into HIV behavioral research. METHODS: Standard RDS
procedures were used to recruit active methamphetamine smokers from a racially
diverse peri-urban township in Cape Town. Effectiveness of RDS was determined by
examining social network characteristics (network size, homophily, and
equilibrium) of recruited participants. RESULTS: Beginning with eight seeds, 345
methamphetamine users were enrolled over 6 months, with a coupon return rate of
67%. The sample included 197 men and 148 women who were racially diverse (73%
Coloured, 27% Black African) and had a mean age of 28.8 years (SD=7.2). Social
networks were adequate (mean network size >5) and mainly comprised of close
social ties. Equilibrium on race was reached after 11 waves of recruitment, and
after <=3 waves for all other variables of interest. There was little to moderate
preference for either in- or out-group recruiting in all subgroups. CONCLUSIONS:
Results suggest that RDS is an effective method for engaging methamphetamine
users into HIV prevention research in South Africa. Additionally, RDS may be a
useful strategy for seeking high-risk methamphetamine users for HIV testing and
linkage to HIV care in this and other low resource settings.
PMID- 25128960
TI - Retinal vessel diameter measurements by spectral domain optical coherence
tomography.
AB - PURPOSE: To describe a spectral domain optical coherence (OCT)-assisted method of
measuring retinal vessel diameters. METHODS: All Patients with an OCT circle scan
centered at the optic nerve head using a Spectralis OCT (Heidelberg Engineering,
Heidelberg, Germany) were retrospectively reviewed. Individual retinal vessels
were identified on infrared reflectance (IR) images and given unique labels both
on IR and spectral domain OCT (SD-OCT). Vessel width and vessel types obtained by
IR were documented as ground truth. From OCT, measurements of each vessel,
including horizontal vessel contour diameter, vertical vessel contour diameter,
horizontal hyperreflective core diameter, and reflectance shadowing width, were
assessed. RESULTS: A total of 220 vessels from 13 eyes of 12 patients were
labeled, among which, 194 vessels (88 arteries and 65 veins confirmed from IR)
larger than 40 microns were included in the study. The mean vessel width obtained
from IR was 107.9 +/- 36.1 microns. A mean vertical vessel contour diameter of
119.6 +/- 29.9 microns and a mean horizontal vessel contour diameter of 124.1 +/-
31.1 microns were measured by SD-OCT. Vertical vessel contour diameter did not
differ from vessel width in all subgroup analysis. Horizontal vessel contour
diameter was not significantly different from vessel width for arteries and had
strong or very strong correlation with vessel width for veins. CONCLUSION: In our
study, vertical vessel contour diameter measured by current commercially
available SD-OCT was consistent with vessel width obtained by IR with good
reproducibility. This SD-OCT based method could potentially be used as a standard
measurement procedure to evaluate retinal vessel diameters and their changes in
ocular and systemic disorders.
PMID- 25128961
TI - Results of long-term monitoring of normal-tension glaucoma patients receiving
medical therapy: results of an 18-year follow-up.
AB - PURPOSE: To conduct a >=15-year follow-up assessment of the visual field (VF) in
normal-tension glaucoma (NTG) patients receiving medical therapy and to identify
risk factors for VF progression. DESIGN: A retrospective clinical study. METHODS:
Medical records of 78 eyes of 78 NTG patients monitored for >=15 years were
reviewed. VF progression was defined by a mean deviation (MD) deteriorated twice
by 3.00 dB from baseline (MD criterion) and an annual decrease in the MD slope
exceeding -0.5 dB/year (MD slope criterion). Logistic regression analysis was
employed to identify risk factors for VF progression. RESULTS: The mean follow-up
period was 18.3 years. The average intraocular pressure (IOP) before treatment
was 15.1 +/-1.9 mmHg and the average treated IOP was 13.5 +/-1.5 mmHg with 2.0
medications. Forty-two eyes (53.8%) showed VF progression using the MD criterion
and 15 eyes (19.2%) showed a negative MD slope less than -0.5 dB/year. Disc
hemorrhage (DH) was observed in 30 eyes (38.5%). The mean VF progression rate was
-0.38 +/-0.30 dB/year in the DH group and -0.24 +/-0.28 dB/year in the non-DH
group (P = 0.012). Multiple logistic regression analysis identified DH [relative
risk (RR) 4.28; P = 0.028] as a risk factor for VF progression using the MD
criterion. DH (RR 8.77; P = 0.007) and IOP fluctuation during follow-up (RR 5.03;
P = 0.048) were detected as risk factors using the MD slope criterion.
CONCLUSIONS: DH and IOP fluctuation were associated with VF progression in NTG
during long-term therapy.
PMID- 25128963
TI - Editorial.
PMID- 25128962
TI - Measurement of retinal nerve fiber layer and macular ganglion cell-inner
plexiform layer with spectral-domain optical coherence tomography in patients
with optic nerve head drusen.
AB - PURPOSE: To evaluate the effect of optic nerve head drusen (ONHD) on the retinal
nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL)
using Cirrus optical coherence tomography (OCT). METHODS: Fifty-seven eyes of
thirty patients with ONHD and thirty-eight eyes of twenty age-matched and sex
matched control subjects underwent circumpapillary and macular scanning using
Cirrus OCT. The percentages of eyes with abnormal GCIPL and RNFL values according
to the Cirrus normative data were analysed and compared. RESULTS: Overall, eyes
with ONHD showed abnormally reduced values for average and minimum GCIPL
thicknesses in 35 % and 45 % of cases compared to 2 % for both values in control
eyes (P < 0.001). Average RNFL thickness comparison between eyes with ONHD and
normal eyes revealed abnormal thinning in 33 % vs. 0 %, respectively (p = 0.002).
The percentage of abnormal thinning increased with higher grades of ONHD for all
the parameters evaluated, so that in grade III drusen, values were abnormally
reduced in 80 % of eyes in all three analyses. Regarding buried ONHD, 30 % and 4
% of eyes had an abnormally reduced minimum GCIPL and average RNFL thickness,
respectively. Furthermore, 26 % of these eyes had abnormal GCIPL exams with a
normal or increased RNFL thickness. CONCLUSIONS: Both RNFL and GCIPL analysis
reveal significant thinning in eyes with ONHD directly correlated with drusen
severity. In buried ONHD, the abnormality rate was significantly higher with
GCIPL compared to RNFL evaluation, suggesting that GCIPL analysis might be an
early structural indicator of neuronal loss in the setting of thickened RNFL.
PMID- 25128964
TI - Twist 1 regulates the expression of PPARgamma during hormone-induced 3T3-L1
preadipocyte differentiation: a possible role in obesity and associated diseases.
AB - BACKGROUND: Twist 1 is highly expressed in adipose tissue and has been associated
with obesity and related disorders. However, the molecular function of Twist 1 in
adipose tissue is unclear. Twist 1 has been implicated in cell lineage
determination and differentiation. Therefore, we investigated both the role of
Twist 1 in adipocyte precursor mobilization and the relationship of Twist 1 with
other molecular determinants of adipocyte differentiation. METHODS: We examined
Twist 1 mRNA and protein expression in subcutaneous adipose tissues from diet
induced obese C57/BL6 mice and Wistar rats and in obese patients undergoing
liposuction or adipose transplant surgeries. Twist 1 expression was measured on
days 0, 2, 4, 8, and 12 of 3T3-L1 differentiation in vitro. The role of Twist 1
in adipogenesis was explored using retroviral interference of Twist 1 expression.
Adipokine secretion was evaluated using a RayBio(r) Biotin Label-based Adipokine
Array. RESULTS: Twist 1 mRNA and protein levels were reduced in diet-induced
obese mice and rats and in obese humans. Twist 1 was upregulated during 3T3-L1
preadipocyte differentiation in vitro, beginning from the fourth day of
differentiation induction. Retroviral interference of Twist 1 expression did not
significantly impair lipid formation; however, retroviral interference induced
PPARgamma mRNA and protein expression on day 4 of differentiation induction.
Adipokine array analyses revealed increased secretion of CXCR4 (19.55-fold),
VEGFR1 (92.13-fold), L-21 R (63.55-fold), and IL-12 R beta 1 (59.66-fold) and
decreased secretion of VEGFR3 (0.01-fold), TSLP R (0.071-fold), MIP-1 gamma
(0.069-fold), TNF RI/TNFRSF1A (0.09-fold), and MFG-E8 (0.06-fold). CONCLUSIONS:
Twist 1 is a regulator of adipocyte gene expression although it is not likely to
regulate differentiation. We identified PPARgamma as a potential target of Twist
1 and found variation in the secretion of multiple adipokines, which might
indicate a prospective mechanism linking Twist 1 expression with obesity or
associated diseases.
PMID- 25128965
TI - Extent of physeal involvement in Legg-Calve-Perthes disease.
AB - PURPOSE: The growth plate involvement (GPI) index is reportedly a reliable
predictor of final radiographic outcome in Legg-Calve-Perthes disease (LCPD). We
determined whether (1) the GPI index was associated with the lateral pillar
classification, (2) the GPI index could predict the final radiographic outcome,
and (3) the geometry of proximal femur was affected by presence of physeal
involvement. METHODS: We reviewed 47 patients with unilateral LCPD who were
treated conservatively. The mean duration of follow-up was 9.5 years (range, five
to 13 years). The affected hips were categorized into those with and without
physeal involvement. Herring classifications were determined and the GPI indices
were estimated at the stage of maximum fragmentation. The Stulberg
classification, leg length discrepancy (LLD), articulotrochanteric distance (ATD)
index, neck-shaft angle (NSA), neck width and height were determined at skeletal
maturity. RESULTS: The GPI indices were lower in Herring groups A and B (p <
0.001) and Stulberg classes I and II (p = 0.002), and these values were increased
in the Herring group B/C and C and Stulberg classes III, IV and V. However, the
age of onset, LLD and ATD index at skeletal maturity were not associated with the
GPI index. The NSA of the affected hips with physeal involvement was
significantly different compared to that of unaffected hips (p < 0.001).
CONCLUSIONS: The GPI index could be used to determine the extent of physeal
involvement in LCPD, and might be considered one of the prognostic values of
radiographic development in patients with LCPD who are treated conservatively.
PMID- 25128966
TI - Primary cementless hip arthroplasty as a potential risk factor for non-union
after long-stem revision arthroplasty in periprosthetic femoral fractures.
AB - PURPOSE: In case of stem loosening in periprosthetic femoral fractures (PPFF),
revision arthroplasty should be performed. The first hypothesis of this study was
that advanced patient age and female gender shows higher non-union rates. The
second hypothesis was that primary cementless arthroplasty is associated with a
higher non-union rate compared to cemented primary hip arthroplasty. METHODS: All
PPFF occurring between January 2000 and June 2010 treated by revision
arthroplasty were included. Multiple regression analysis was performed to
identify independent variables leading to fracture non-union. RESULTS: Eighty one
patients (78 % female) met the inclusion criteria. In 20/81 patients (24.7 %) no
adequate fracture healing could be determined on radiographs 12 months after
revision surgery. Although age and female gender showed a positive correlation
with bony non-union after PPFF as expected, the p-values were not statistically
significant. Multiple regression analysis revealed primary cementless prosthesis
(p = 0.001) to be the only independent variable associated with non-union.
CONCLUSION: Non-cemented primary prosthesis might be a negative predicting factor
for the development of non-union after long-stem revision arthroplasty in PPFF.
We therefore recommend the thorough debridement of pannus tissue thus inducing
bone healing before the implantation of revision prostheses.
PMID- 25128967
TI - Pre-operative scoring system to determine the surgical strategy for
periprosthetic hip infection.
AB - PURPOSE: The aim of this study was to evaluate the results of one- and two-stage
revision total hip arthroplasties (THAs) and to determine a rational surgical
treatment strategy for periprosthetic hip infections. METHODS: We constructed a
12-point preoperative scoring system to suggest either one- or two-stage revision
THAs, based on a retrospective analysis of 55 operative procedures. Prosthesis
survival was analysed using the Kaplan-Meier method, and the validity of the
scoring system was evaluated using receiver-operating characteristic curves.
RESULTS: At the end point of implant removal due to recurrent infection, the ten
year survival rates were 94 and 87% for one- and two-stage revision THAs,
respectively. One-stage revision THA was recommended for patients scoring >9
points. The risk of recurrent infection in patients scoring 4 points was 83%. The
sensitivity and specificity of a cut-off value of 4 points, determined by the
scoring system, were 83 and 100%, respectively. CONCLUSIONS: The novel pre
operative scoring system was useful for the management of periprosthetic hip
infections.
PMID- 25128968
TI - A comparison of ACL reconstruction using patellar tendon versus hamstring
autograft in female patients: a prospective randomised study.
AB - PURPOSE: The incidence of an anterior cruciate ligament (ACL) tear is highest in
female patients; however, it is not apparent whether graft choice affects
clinical results. The aim of this prospective randomised study was to evaluate
clinical results of an ACL reconstruction using patellar tendon [bone-patellar
tendon-bone (BTB)] or hamstring graft (HS) in female patients. METHODS: Inclusion
criteria were traumatic instability, no signs of osteoarthritis, no previous
instability and no contralateral knee instability. Inclusion criteria were met in
150 patients, mean age 26 (17-47) years. Patients were randomised into two groups
of 75 patients according to graft type; all had the same rehabilitation protocol.
Tegner Lysholm knee score and stability were evaluated pre-operatively and one
and two years postoperatively. The difference between groups was statistically
evaluated using unpaired t test. RESULTS: Of the 150 patients, all completed one
year follow-up; three were lost to follow-up at two years. There was no
significant difference in functional scores and knee stability between groups.
The HS group had significantly less anterior knee pain in the first six months
postoperatively. CONCLUSION: ACL reconstruction significantly improves clinical
results and stability of the knee. Difference in Lysholm score and stability
between groups was not significant. Neither group showed higher tendency to graft
failure within two years. Graft choice for reconstruction in female patients
should be surgeon specific and individualised, as both grafts studied achieved
comparable results.
PMID- 25128969
TI - Third-generation minimally invasive correction of hallux valgus: technique and
early outcomes.
AB - PURPOSE: There is growing evidence supporting minimally invasive surgical (MIS)
techniques for correction of symptomatic hallux valgus. The aim of this study was
to present a hybrid third-generation technique and assess the safety and efficacy
from the first 45 procedures. METHODS: Forty-five consecutive feet underwent a
third-generation MIS distal chevron osteotomy with a minimum six month follow-up
(range six to 17 months). This technique uses both first- and second-generation
techniques plus a distal chevron osteotomy and screw for improved control and
stabilisation of the metatarsal head. All patients were clinically assessed using
the Manchester-Oxford Foot Questionnaire (MOXFQ). Radiographic measures included
hallux valgus angle (HVA), intermetatarsal angle (IMA), first metatarsal length
and overall toe length. RESULTS: There were significant improvements in all three
domains of the MOXFQ (p <0.001). There was also significant improvement in all
radiographic parameters (p < 0.001). Mean HVA decreased from 30.54 degrees to
10.41 degrees , and the mean IMA decreased from 14.55 degrees to 7.11 degrees .
Shortening of the first metatarsal had no effect on clinical outcomes. There was
a very low rate of complications. CONCLUSION: The short-term results of this
third-generation technique show that it is a safe procedure with good clinical
outcomes and compares favourably with earlier techniques.
PMID- 25128970
TI - Editorial overview: virus-glycan interactions and pathogenesis.
PMID- 25128971
TI - The effects of coronary artery calcium screening on behavioral modification, risk
perception, and medication adherence among asymptomatic adults: a systematic
review.
AB - OBJECTIVE: To perform systematic review of the effects of screening for coronary
artery calcium (CAC), a subclinical marker of coronary artery disease (CAD), on
behavioral or lifestyle modification, risk perception, and medication adherence.
METHODS: We searched through CINAHL, PsychInfo, Web of Science, Cochrane Central
Register of Control Trials, and PubMed (Medline) for studies on the effects of
CAC screening in asymptomatic individuals across three major domains: behavioral
modification, risk perception for CAD, and medication adherence. We extracted
data from the retrieved studies, assessed and synthesized the information.
RESULTS: Of the 15 retrieved studies, three were randomized control trials and 12
were observational studies. CAC score was ascertained either as total score,
quartiles, or standardized Agatston's ordinal scale. While all the 15 studies
involved issues related to behavioral and medication adherence, four involved
risk perception of CAD. Although no standardized approach was used in these
studies, CAC screening enhanced medication adherence in 13 of the 15 studies,
while the others were mixed. CONCLUSION: CAC screening improved medication
adherence and could likely motivated individuals for beneficial behavioral or
lifestyle changes to improve CAD. The mixed results suggest the need for further
research because screening for subclinical atherosclerosis has significant
implications for early detection and prevention of future cardiovascular events
by aggressive risk factors modification.
PMID- 25128972
TI - Vulnerable plaque: the biomechanics of matter.
PMID- 25128973
TI - Distinct phenotypes of cardiac allograft vasculopathy after heart
transplantation: a histopathological study.
AB - INTRODUCTION: Long-term survival after heart transplantation (HTx) is hampered by
cardiac allograft vasculopathy (CAV). Better understanding of the
pathophysiological mechanisms of CAV might have considerable consequences for
therapeutic approaches in the future. The aim of the present study was to
investigate the histological phenotypes of CAV in relation with clinical patient
characteristics. METHODS AND RESULTS: Coronary cross-sections from 51 HTx
patients were obtained at autopsy. CAV was observed in 42 patients (82%). Three
histological CAV phenotypes were identified (H-CAV 1-3). No CAV (H-CAV 0) is as
seen in normal coronary arteries; intimal thickening consisting of a layer of
longitudinal oriented smooth muscle cells. In H-CAV 1 to 3 a second intimal layer
is formed, on top of the longitudinal oriented smooth muscle cell layer, with
predominantly mononuclear inflammatory infiltrate in loose connective tissue (H
CAV 1), smooth muscle cells in different orientation (H-CAV 2), or a fibrotic
intimal lesion (H-CAV 3). H-CAV type was significantly related with time after
transplantation, age at transplantation, the amount of atherosclerotic disease
and the occurrence of infection. In addition, morphometric analysis revealed that
higher H-CAV types have a relatively larger intimal area, that is compensated for
by expansive arterial remodeling of the artery. CONCLUSION: CAV in an ongoing
process that can be classified into three different phenotypes; inflammatory
lesions, lesions rich of smooth muscle cells and fibrotic lesions. Our results
suggest that these phenotypes are related to time after transplantation, age at
transplantation, the amount of atherosclerotic disease and the occurrence of
infection.
PMID- 25128975
TI - The use of pneumatic tourniquet in total knee arthroplasty: a meta-analysis.
AB - BACKGROUND: Pneumatic tourniquet use in total knee arthroplasty (TKA) is always a
controversial issue. The aim of the present study is to assess the effectiveness
and safety of its use in patients receiving primary unilateral TKA, and to
explore the most safe and effective protocols. MATERIALS AND METHODS: This review
was based on cochrane methodology for conducting meta-analysis. Only randomized
controlled trials (RCTs) were eligible for this study. The participants were
adults who had undergone primary unilateral TKA. The Review Manager Database
(RevMan version 5.0, The Cochrane Collaboration 2008) was used to analyze the
dates of the selected studies. RESULTS: Thirteen RCTs involving 859 patients were
included in this analysis. The use of tourniquet could significantly reduce
operation time (mean difference -5.01 min, P = 0.003), intraoperative blood loss
(mean difference -201.85 ml, P < 0.00001) and total blood loss volumes (mean
difference -125.03 ml, P = 0.61). But postoperative (mean difference 45.99 ml, P
= 0.68) were slightly increased in that situation. With respect to surgical
complications, a tendency of increasing risk ratio was observed for tourniquet
group. CONCLUSIONS: Our results indicate that tourniquet application could reduce
surgical time, intraoperative blood loss and total blood loss, but increases
postoperative total blood loss. With respect to postoperative complications, DVT
and surgical site infection rates are relatively augmented in the tourniquet
group.
PMID- 25128974
TI - Association of vascular endothelial factors with cardiovascular outcome and
mortality in chronic kidney disease patients: a 4-year cohort study.
AB - BACKGROUND: Angiogenic cytokines fms-like tyrosine kinase-1(sFlt-1) and placental
growth factor (PlGF) are associated with increased risk for cardiovascular
disease (CVD) in the general population. In this study we examine the association
between these vascular endothelial factors and atherosclerosis, cardiovascular
outcome, and mortality in chronic kidney disease (CKD) patients. METHODS: Serum
level of PlGF and sFlt-1 were measured in 301 patients with CKD, who were
followed for up to 4 years. Primary outcomes were CV events and all-cause
mortality. Carotid-intima media thickness (CIMT) was used as marker of
atherosclerosis. Kaplan-Meier survival curves and the Cox proportional hazard
model were used to assess the association of biomarkers and clinical outcomes.
RESULTS: Mean (SD) PlGF and sFlt-1 were 5.45 ng/ml (3.76) and 68.6 (28.0) pg/ml,
respectively. During the follow up time, 60 patients (19.9%) experienced CV
events and 22 patients (7.3%) died. Compared with low PlGF, patients with PlGF
above median level had higher CV events (12.7% vs. 27.2%, p = 0.002) and
mortality (2.0% vs. 12.6%, p < 0.001). The associations of PlGF and sFlt-1 with
CV events were not statistically significant in the fully adjusted model. Higher
PlGF was associated with greater death risk (HR = 5.22, 95% CI: 1.49-18.33, p =
0.01), which was robust to adjustment for sFlt-1 and other risk factors. Elevated
sFlt-1 level was also an independent predictor of mortality (HR 3.41, 95% CI:
1.49-9.51, p = 0.019). CONCLUSION: In CKD patients not yet on dialysis, higher
serum level of PlGF and sFlt-1 are associated with increased mortality, but not
CV events.
PMID- 25128976
TI - Multiplexed aberration measurement for deep tissue imaging in vivo.
AB - We describe an adaptive optics method that modulates the intensity or phase of
light rays at multiple pupil segments in parallel to determine the sample-induced
aberration. Applicable to fluorescent protein-labeled structures of arbitrary
complexity, it allowed us to obtain diffraction-limited resolution in various
samples in vivo. For the strongly scattering mouse brain, a single aberration
correction improved structural and functional imaging of fine neuronal processes
over a large imaging volume.
PMID- 25128978
TI - Pathobiology of Mycoplasma suis.
AB - Mycoplasma suis is an uncultivable bacterium lacking a cell wall that attaches to
and may invade the red blood cells of pigs. M. suis infections occur worldwide
and cause the pig industry serious economic losses due to the disease known as
infectious anaemia of pigs or, historically, porcine eperythrozoonosis.
Infectious anaemia of pigs is characterised predominantly by acute haemolytic or
chronic anaemia, along with non-specific manifestations, such as growth
retardation in feeder pigs and poor reproductive performance in sows. The
fastidious nature of M. suis, as well as the lack of an in vitro cultivation
system, has hampered the understanding of the biology and pathogenicity of this
organism. Pathogenetic mechanisms of M. suis include direct destruction of red
blood cells by adhesion, invasion, nutrient scavenging, immune-mediated lysis and
eryptosis, as well as endothelial targeting. Recently published genome sequences,
in combination with proteome analyses, have generated new insights into the
pathogenicity of M. suis. The present review combines these data with the
knowledge provided by experimental M. suis infections.
PMID- 25128977
TI - Accurate de novo and transmitted indel detection in exome-capture data using
microassembly.
AB - We present an open-source algorithm, Scalpel (http://scalpel.sourceforge.net/),
which combines mapping and assembly for sensitive and specific discovery of
insertions and deletions (indels) in exome-capture data. A detailed repeat
analysis coupled with a self-tuning k-mer strategy allows Scalpel to outperform
other state-of-the-art approaches for indel discovery, particularly in regions
containing near-perfect repeats. We analyzed 593 families from the Simons Simplex
Collection and demonstrated Scalpel's power to detect long (>=30 bp) transmitted
events and enrichment for de novo likely gene-disrupting indels in autistic
children.
PMID- 25128979
TI - Accumulation of artificial radionuclides in agricultural plants in the area used
for surface nuclear tests.
AB - The paper reports on the study of artificial radionuclide accumulation in
agricultural crops grown at the territory with high concentration of
radionuclides, and first of all - with high concentration of transuranium
elements. As a result of this work, peculiarities of accumulation and
distribution of artificial radionuclides in the vegetative and generative organs
of the studied plants have been revealed. Basic accumulation factors have been
found for (137)Cs, (90)Sr, (239+240)Pu, and (241)Am in agricultural products.
Accumulation factor dependence on type of planting was found for the investigated
types of plants. It has been found that the vegetative organs accumulate
radionuclides most of all.
PMID- 25128980
TI - Extracorporeal membrane oxygenation in adults for severe acute respiratory
failure.
AB - The purpose of this review is to examine the indications of extracorporeal
membrane oxygenation (ECMO) for severe acute respiratory distress syndrome
(ARDS). This technique of oxygenation has significantly increased worldwide with
the H1N1 flu pandemic. The goal of ECMO is to maintain a safe level of
oxygenation and controlled respiratory acidosis under protective ventilation. The
enthusiasm for ECMO should not obscure the consideration for potential associated
complications. Before widespread diffusion of ECMO, new trials should test the
efficacy of early initiation or CO2 removal in addition to, or even as an
alternative to mechanical ventilation for severe ARDS.
PMID- 25128983
TI - China seeks creative ways to combat smog.
PMID- 25128981
TI - The molecular symplesiomorphies shared by the stem groups of metazoan evolution:
can sites as few as 1% have a significant impact on recognizing the phylogenetic
position of myzostomida?
AB - Although it is clear that taxon sampling, alignments, gene sampling, tree
reconstruction methods and the total length of the sequences used are critical to
the reconstruction of evolutionary history, weakly supported or misleading nodes
exist in phylogenetic studies with no obvious flaw in those aspects. The
phylogenetic studies focusing on the basal part of bilaterian evolution are such
a case. During the past decade, Myzostomida has appeared in the basal part of
Bilateria in several phylogenetic studies of Metazoa. However, most researchers
have entertained only two competing hypotheses about the position of Myzostomida
an affinity with Annelida and an affinity with Platyhelminthes. In this study,
dozens of symplesiomorphies were discovered by means of ancestral state
reconstruction in the complete 18S and 28S rDNAs shared by the stem groups of
Metazoa. By contrastive analysis on the datasets with or without such
symplesiomorphic sites, we discovered that Myzostomida and other basal groups are
basal lineages of Bilateria due to the corresponding symplesiomorphies shared
with earlier lineages. As such, symplesiomorphies account for approximately 1-2%
of the whole dataset have an essential impact on phylogenetic inference, and this
study reminds molecular systematists of the importance of carrying out ancestral
state reconstruction at each site in sequence-based phylogenetic studies. In
addition, reasons should be explored for the low support of the hypothesis that
Myzostomida belongs to Annelida in the results of phylogenomic studies. Future
phylogenetic studies concerning Myzostomida should include all of the basal
lineages of Bilateria to avoid directly neglecting the stand-alone basal position
of Myzostomida as a potential hypothesis.
PMID- 25128984
TI - Human melanocytes form a PAX3-expressing melanocyte cluster on Matrigel by the
cell migration process.
AB - BACKGROUND: The interactions between human epidermal melanocytes and their
cellular microenvironment are important in the regulation of human melanocyte
functions or in their malignant transformation into melanoma. Although the
basement membrane extracellular matrix (BM-ECM) is one of major melanocyte
microenvironments, the effects of BM-ECM on the human melanocyte functions are
not fully explained at a molecular level. OBJECTIVE: This study was aimed to
characterize the molecular and cellular interactions between normal human
melanocytes (NHMs) and BM-ECM. METHODS: We investigated cell culture models of
normal human melanocytes or melanoma cells on three-dimensional (3D) Matrigel to
understand the roles of the basement membrane microenvironment in human
melanocyte functions. Melanogenesis and melanobast biomarker expression in both
primary human melanocytes and melanoma cells on 3D Matrigel were evaluated.
RESULTS: We found that NHMs migrated and formed reversible paired box 3 (PAX3)
expressing cell clusters on three-dimensional (3D) Matrigel. The melanogenesis
was significantly decreased in the PAX3 expressing cell cluster. The expression
profile of PAX3, SOX10, and MITF in the melanocyte cluster on 3D Matrigel was
similar to that of melanoblasts. Interestingly, PAX3 and SOX10 showed an inverse
expression profile in NHMs, whereas the inverse expression pattern of PAX3 and
SOX10 was disrupted in melanoma MNT1 and WM266-4 cells. CONCLUSION: The human
melanocyte culture on 3D Matrigel provides an alternative model system to study
functions of human melanoblasts. In addition, this system will contribute to the
elucidation of PAX3-related tumorigenic mechanisms to understand human melanoma.
PMID- 25128985
TI - Development and clinical evaluation of a novel fully automated qualitative PCR
assay for the diagnosis of anogenital herpes simplex virus infection.
AB - Molecular detection of viral infections has the potential to improve microbial
diagnostics, particularly with the emergence of rapid automated systems. We
describe the design of the IDbox fully automated cassette-based system for
nucleic acid extraction and real-time PCR amplification and perform a clinical
evaluation for the diagnosis of genital herpes simplex infections. At optimal
cutoff values determined by receiver-operator curves, the IDbox showed
sensitivities of 94.9% (95% confidence interval [CI] 84.9-98.7%) and 97.0% (95%
CI 88.5-99.5%) and specificities of 96.7% (95% CI 91.2-98.9%) and 97.3% (95% CI
91.9-99.3%) relative to herpes simplex virus culture and PCR, respectively. We
discuss relevant design characteristics and approaches used for each step of the
analytical process to enhance assay sensitivity and provide accurate results in
the presence of potential cross-reactive organisms and interfering substances.
PMID- 25128982
TI - A tree of cellular life inferred from a genomic census of molecular functions.
AB - Phylogenomics aims to describe evolutionary relatedness between organisms by
analyzing genomic data. The common practice is to produce phylogenomic trees from
molecular information in the sequence, order, and content of genes in genomes.
These phylogenies describe the evolution of life and become valuable tools for
taxonomy. The recent availability of structural and functional data for hundreds
of genomes now offers the opportunity to study evolution using more deep,
conserved, and reliable sets of molecular features. Here, we reconstruct trees of
life from the functions of proteins. We start by inferring rooted phylogenomic
trees and networks of organisms directly from Gene Ontology annotations.
Phylogenies and networks yield novel insights into the emergence and evolution of
cellular life. The ancestor of Archaea originated earlier than the ancestors of
Bacteria and Eukarya and was thermophilic. In contrast, basal bacterial lineages
were non-thermophilic. A close relationship between Plants and Metazoa was also
identified that disagrees with the traditional Fungi-Metazoa grouping. While
measures of evolutionary reticulation were minimum in Eukarya and maximum in
Bacteria, the massive role of horizontal gene transfer in microbes did not
materialize in phylogenomic networks. Phylogenies and networks also showed that
the best reconstructions were recovered when problematic taxa (i.e.,
parasitic/symbiotic organisms) and horizontally transferred characters were
excluded from analysis. Our results indicate that functionomic data represent a
useful addition to the set of molecular characters used for tree reconstruction
and that trees of cellular life carry in deep branches considerable predictive
power to explain the evolution of living organisms.
PMID- 25128987
TI - Resistance to nucleotide analogue inhibitors of hepatitis C virus NS5B:
mechanisms and clinical relevance.
AB - The high barrier to the development of resistance to nucleotide analogue
inhibitors of the hepatitis C virus (HCV) RNA-dependent RNA polymerase is an
intriguing property of this class of drugs. The S282T substitution in the viral
polymerase confers resistance to 2'-C-methylated nucleotide analogues. Although
this mutation can be selected in HCV replicons, it has only been identified in
very few cases in the clinic. Alternative resistance pathways are likewise rarely
seen in vivo. Possible underlying mechanisms that are associated with the
selection and establishment of a resistant genotype are discussed in this review.
PMID- 25128989
TI - Misery of mystery of Muzaffarpur.
PMID- 25128988
TI - Sodium channel point mutations associated with pyrethroid resistance in Chinese
strains of Culex pipiens quinquefasciatus (Diptera: Culicidae).
AB - BACKGROUND: Pesticide resistance due to sodium channel point mutations has been
well documented in many mosquito species. METHODS: We tested the resistance of
six, wild, Chinese populations of the mosquito Culex pipiens quinquefasciatus to
deltamethrin and cyhalothrin. The full length of the sodium channel gene was
cloned and sequenced from a pooled sample of mosquitoes from each population.
RESULTS: Seven amino acid alterations were found (V250M, R436K, M943V, I973T,
L1035F, L1035S and E1901D). Correlation between the frequencies of these
mutations and the level of pesticide resistance (LC50) associated with them
indicates that those at position L1035 (corresponding to position L1014F in the
house fly, Musca domestica; GenBank Accession No.: X96668) are associated with
resistance to deltamethrin and cyhalothrin. The frequency of the L1035F mutation
was significantly correlated with resistance to deltamethrin (R2 = 0.536, P =
0.049) and cyhalothrin (R2 = 0.626, P = 0.030), and the combined frequency of the
L1035F and L1035S mutations was significantly correlated with resistance to both
deltamethrin (R2 = 0.661, P = 0.025), and cyhalothrin (R2 = 0.803, P = 0.008).
None of the other mutations were correlated with either deltamethrin or
cyhalothrin resistance. Interestingly, an HWE test indicated significant linkage
between the M943V and I973T mutations (P < 0.01), but further research is
required to determine the biological significance of this linkage. CONCLUSIONS:
Identifying these mutations may be of practical benefit to the development of
pesticide resistance management programs.
PMID- 25128990
TI - Diagnostic tool for neuromotor impairment for primary care physician.
PMID- 25128991
TI - Indigenous diagnostic tool for neuromotor impairments for primary care physician.
PMID- 25128992
TI - Predictors of mortality in neonates with meconium aspiration syndrome.
PMID- 25128994
TI - Effects of elevated blood lead levels in preschool children in urban Vellore.
AB - OBJECTIVE: To study the burden and associated risk factors for elevated blood
lead levels among pre-school children (15-24 months) in urban Vellore, and to
study its effects on child cognition and anemia. DESIGN: An investigative study
through Mal-ED cohort. SETTING: Eight adjacent urban slums in Vellore, Tamil
Nadu. PARTICIPANTS: 251 babies recruited through Mal-ED Network. OUTCOME
MEASURES: Blood lead levels using Graphite Furnace Atomic Absorption
Spectrophotometry method at 15 and 24 mo; hemoglobin estimation by
azidemethemoglobin method; cognitive levels using Bayley Scales of Infant
Development III. RESULTS: Around 45% of children at 15 months and 46.4% at 24
months had elevated blood lead levels (>10 ug/dL). Among children who had
elevated blood lead levels at 15 months, 69.2% (45/65) continued to have elevated
levels at 24 months. After adjusting for potential confounders, children from
houses having a piped drinking water supply and houses with mud or clay floors
were at significantly higher risk of having elevated blood lead levels at 15
months. Thirty one percent (21/67) of the children with elevated blood lead
levels had poor cognitive scores. Children with elevated blood lead levels at 15
months had higher risk (Adjusted OR 1.80; 95% CI 0.80 - 3.99) of having poorer
cognitive scores at 24 months. More than half of the children (57%) were anemic
at 15 months of age, and elevated blood lead levels were not significantly
associated with anemia. CONCLUSIONS: Elevated blood lead levels are common among
preschool children living in urban slums of Vellore. Poorer conditions of the
living environment are associated with elevated lead levels.
PMID- 25128993
TI - INCLEN Diagnostic Tool for Neuromotor Impairments (INDT-NMI) for primary care
physician: development and validation.
AB - OBJECTIVE: To develop and validate a diagnostic tool for use by primary care
physicians for diagnosing neuro-motor impairment among 2-9 year old children in
primary care settings. STUDY DESIGN: Modified Delphi technique involving national
(n=49) and international (n=6) experts was used for development of INDT-NMI. The
tool was then validated through a cross sectional study. SETTING: Neurology
specialty clinics of three tertiary care pediatric centers in New Delhi, India.
PARTICIPANTS: 454 children aged 2-9 years [mean (SD) age: 60.4 (23.7) mo],
selected through systematic random sampling, underwent assessment for
identification and classification of neuromotor impairments (NMI). INTERVENTION:
All study subjects were first administered INDT-NMI (candidate test) by a trained
physician followed by expert assessment for NMI and other neurodevelopment
disorders (NDD) by team of two pediatric neurologists (Gold standard). RESULTS:
According to expert evaluation, 171 (37.8%) children had neuromotor impairments.
There were four categories of subjects: NMI alone (n=66); NMI+other NDDs (n=105);
Other NDDs without NMI (n=225) and 'Normal' group (n=58). Using expert evaluation
as gold standard, overall sensitivity of the INDT-NMI was 75.4% and specificity
was 86.8%. INDT-NMI helped graduate physicians to correctly classify 86.6%
(112/129) children with NMI into different types (cerebral palsy, neuromotor
diseases and other NMI). Graduate physicians assigned 40 children (8.8%) as
'indeterminate', 38 (95%) of whom had either NDD and/or NMI and thus merited
referral. Misclassification of NMI occurred in those with mild changes in muscle
tone, dystonia, or ataxia and associated NDDs. CONCLUSIONS: Graduate primary care
physicians with a structured short training can administer the new tool and
diagnose NMI in 2-9 year old children with high validity. INDT-NMI requires
further evaluation in actual primary care settings.
PMID- 25128995
TI - Incorporating developmental screening and surveillance of young children in
office practice.
AB - CONTEXT: Developmental concerns voiced by parents need to be responded to by
structured developmental screening. Screening is the use of validated
developmental screening tools to identify children with high risk of
developmental delay out of an apparently normal population, while surveillance is
the process of monitoring children identified as high risk by screening. Absence
of routine screening can be attributed to problems at the level of parents,
pediatricians or National policies. Hence vulnerable children are not detected
early, and are denied benefit from appropriate developmental interventions. There
are no definite guidelines for screening or for suitable tools for screening and
surveillance. OBJECTIVES: To review existing developmental screening and
monitoring tools for children validated in Indian under-five children, and
provide a proposed practice paradigm for developmental screening in office
practice. EVIDENCE ACQUISITION: Scientific papers were retrieved by an electronic
database search using MeSH terms 'screening tool', 'developmental delay', and
filter of 'children under 5 years'. Those relevant to office practice and
validated internationally or in Indian children were reviewed. RESULTS: Screening
tools applicable to Indian office practice have been compared and certain tools
have been recommended according to the level of risk of developmental delay. An
algorithmic approach to screening has been given along with strategies for
incorporation. CONCLUSIONS: Screening and surveillance for high risk of
developmental delay are essential components of child health care. It is possible
to incorporate both into routine practice.
PMID- 25128996
TI - Predictors of mortality in neonates with meconium aspiration syndrome.
AB - OBJECTIVE: To identify risk factors for mortality in neonates with meconium
aspiration syndrome. METHODS: All neonates (2004-2010) with meconium aspiration
syndrome, irrespective of gestation were included. Risk factors were compared
between those who died and survived. RESULTS: Out of 172 included neonates, 44
(26%) died. Mean (SD) gestation and birth weight were 37.9 (2.3) weeks and 2545
(646g), respectively. Myocardial dysfunction [aOR 28.4; 95% CI (8.0-101);
P<0.001] and higher initial oxygen requirement [aOR 1.04; 95% CI (1.02-1.07);
P<0.001] increased odds of dying while a higher birth weight [aOR 0.998; 95% CI
(0.997-1.00); P=0.005] reduced the odds of dying. CONCLUSIONS: Meconium
aspiration syndrome is associated with significant mortality. Myocardial
dysfunction, birth weight, and initial oxygen requirement are independent
predictors of mortality.
PMID- 25128997
TI - Multicystic dysplastic kidney: a retrospective study.
AB - OBJECTIVE: To report the renal structural and functional anomalies in children
with multicystic dysplastic kidneys. METHODS: Retrospective descriptive analysis
of 47 children with multicystic dysplastic kidney seen in a pediatric nephrology
unit over a period of 6 years. RESULTS: Antenatal diagnosis of multicystic
dysplastic kidney was made in 34 (72.3%) patients. On follow up of 31 children
for more than 12 months, 21 (68%) had involution, 4 [13%] had non-regression, and
4 (13%) were nephrectomized. Vesico-ureteric reflux (n=13; 28%) was the commonest
renal abnormality. The serum creatinine values were higher (P=0.006) in children
with contralateral reflux. Sub-nephrotic proteinuria was noted in 9 (29%) and was
significantly associated with complete involution (P=<0.023). None of the
patients developed hypertension and 2 (6.4%) had renal failure. CONCLUSIONS:
Close nephrological follow-up is needed in children with multicystic dysplasia of
kidneys.
PMID- 25128998
TI - Off-label use of drugs in neonatal intensive care units.
AB - OBJECTIVE: To estimate proportion of off-label medication use in neonates and to
evaluate evidence of efficacy and safety of these medications. METHODS: Chart
audit in neonatal intensive care units of two institutions in Chandigarh, India.
RESULTS: Among 568 prescriptions in 156 neonates, 286 (50%) were off-label. Of
these, 56% drugs were not approved for use in neonatal age group and 26%
prescriptions were off-label for frequency, dose, indication, route or rate. Most
common off-label drugs were anti-infective and antiepileptic. Despite lack of
regulatory approval, one-third off-label drugs had level I-II evidence of safety
and efficacy for use in neonates. CONCLUSION: Use of off-label drugs is common in
sick neonates.
PMID- 25128999
TI - A mathematical algorithm for detection of late-onset sepsis in very-low birth
weight infants: a preliminary diagnostic test evaluation.
AB - OBJECTIVE: To study the diagnostic ability of RALIS (computerized mathematical
algorithm and continuous monitoring device) to detect late onset sepsis among
very low birth weight preterm neonates. METHODS: Randomly chosen 24 very low
birth weight infants with proven sepsis were compared to 22 infants without
sepsis. The clinical parameters were retrospectively collected from the medical
records. The ability of RALIS to detect late onset sepsis was calculated.
RESULTS: RALIS positively identified 23 of the 24 infants with sepsis
(sensitivity 95.8%). It indicated sepsis alert median 2.0 days earlier than
clinical suspicion. A false positive alert was indicated in 23% (5/22) infants.
The specificity, and positive and negative predictive ability of RALIS were
77.3%. 82.1% and 94.4%, respectively. CONCLUSION: RALIS may aid in the early
diagnosis of late onset sepsis in very low birth weight preterm infants.
PMID- 25129000
TI - Clinical profile of scrub typhus in children and its association with
hemophagocytic lymphohistiocytosis.
AB - OBJECTIVE: To study the clinical profile of children with scrub typhus and its
association with hemophagocytic lymphohistiocytosis. METHODS: Children presenting
with unexplained fever and multi-systemic involvement between May to December
2011 were tested for scrub typhus using IgM ELISA kits. Occurrence of
Hemophagocytic lymphohistiocytosis in IgM positive cases of scrub typhus was
studied. RESULTS: Of the 35 children with unexplained fever and multi-systemic
involvement, 15 children (9 boys) tested positive for scrub typhus.
Thrombocytopenia, hypoalbuminemia and raised hepatic transaminases were observed
in all children. Out of seven children evaluated for hemophagocytic
lymphohistiocytosis. 3 met the criteria for hemophagocytosis. Two children (one
with hemophagocytic lymphohistiocytosis) died. CONCLUSIONS: Scrub typhus is a
common cause of unexplained fever in children in northern India. Hemophagocytic
lymphohistiocytosis can occasionally complicate scrub typhus in children.
PMID- 25129001
TI - Educating fathers to improve breastfeeding rates and paternal-infant attachment.
AB - OBJECTIVE: To determine the effect of breastfeeding education provided to fathers
on breastfeeding rates and paternal-infant attachment. METHODS: 117 couples with
their infants with the inclusion criteria: knowledge of reading, writing and
speaking Turkish; living in the Turkish Republic of North Cyprus until their
infants were six months old; and infants having no health problems preventing the
early initiation of breastfeeding. Participants were divided into 3 groups (2
experimental and 1 control). Breastfeeding education was provided to the mothers
(20 min/d) in the first group (n=38) and to the mothers and fathers in the second
group (n=39) (20 min/d/parent) until they were discharged from the hospital. This
education was supplemented by a training booklet. The parents and their infants
were followed until the infants were six months old. Exclusive breastfeeding
rates and Paternal-Infant Attachment Scale scores at six months were main outcome
measures. RESULTS: Exclusive breastfeeding rates (56.4%, 33.3% and 12.8%;
P<0.001) and mean (SD) Paternal-Infant Attachment Scale scores [89.51(7.05),
82.37 (12.80) and 73.38 (18.67); P<0.001] were highest in the group where
education was provided to both mother and father. CONCLUSIONS: Providing
breastfeeding education to fathers increases exclusive breastfeeding rates and
strengthens paternal attachment.
PMID- 25129005
TI - An atypical case of parotid gland swelling and arthritis in a child.
AB - BACKGROUND: Early onset sarcoidosis is a rarely reported disease in children.
CASE CHARACTERISTICS: 21/2-year-old girl with chronic enlargement of bilateral
parotid glands and polyarthritis. OBSERVATION: Biopsy of salivary gland revealed
non-caseating granuloma. OUTCOME: Polyarthritis and salivary gland swelling
resolved completely after starting oral corticosteroids. MESSAGE: Sarcoidosis is
an important differential diagnosis in young children with joint and salivary
gland involvement.
PMID- 25129006
TI - Successful conversion of post-cardiac surgery electric storm in a child.
AB - BACKGROUND: The management of ventricular electrical storm can prove to be a
challenge for the clinician given its complexity and life threatening
consequences. CASE CHARACTERISTICS: 8-year-old boy with repeated life-threatening
polymorphic ventricular tachycardia following aortic valve replacement surgery.
INTERVENTION: Defibrillated 45 times in addition to multiple antiarrhythmic
drugs. OUTCOME: Conversion to stable sinus rhythm with normal neurological
outcome. MESSAGE: Electric storm can be controlled by combination of multiple
intravenous antiarrhythmic drugs.
PMID- 25129007
TI - Mitochondrial DNA depletion syndrome causing liver failure.
AB - BACKGROUND: Mitochondrial DNA depletion syndromes are disorders of Mitochondrial
DNA maintenance causing varied manifestations, including fulminant liver failure.
CASE CHARACTERISTICS: Two infants, presenting with severe fatal hepatopathy.
OBSERVATION: Raised serum lactate, positive family history (in first case), and
absence of other causes of acute liver failure. OUTCOME: Case 1 with homozygous
mutation, c.3286C>T (p.Arg1096Cys) in POLG gene and case 2 with compound
heterozygous mutations, novel c.408T>G (p.Tyr136X) and previously reported
c.293C>T (p.Pro98Leu), in MPV17 gene. MESSAGE: Mitochondrial DNA depletion
syndrome is a rare cause of severe acute liver failure in children.
PMID- 25129008
TI - Immune reconstitution inflammatory syndrome in CNS tuberculosis.
AB - BACKGROUND: Immune Reconstitution Inflammatory Syndrome (IRIS), an exaggerated
inflammatory response with clinical worsening due to immune recovery during
treatment, is rare in the immune-competent population. CASE CHARACTERISTICS: A 5
1/2-year old immune-competent girl with CNS tuberculosis without HIV who
developed paradoxical IRIS. OUTCOME: Response to supportive care along with Anti
tuberculosis treatment. MESSAGE: IRIS can occur in tuberculosis, even in the
immuno-competent.
PMID- 25129009
TI - Supplementary suckling technique for relactation in infants with severe acute
malnutrition.
AB - We report on use of supplementary suckling technique in 62 infants [mean (SD) age
2.5 (1.3) mo] with severe acute malnutrition admitted at our Nutritional
rehabilitation Center. It was successful in 34 (55.7%) infants.
PMID- 25129010
TI - A modified technique for umbilical arterial catheterization.
AB - A modified technique for umbilical artery catheterization was assessed in babies
in whom conventional method failed or if the cord was dry. Success rate attained
with the modified technique was 90% (19/21). This modified technique could
provide an easier and faster method for successful umbilical arterial
catheterization.
PMID- 25129011
TI - Transient bulging fontanelle after measles vaccination.
PMID- 25129012
TI - Onychomadesis.
PMID- 25129013
TI - Acute hemorrhagic edema of infancy.
PMID- 25129014
TI - X-linked ichthyosis.
PMID- 25129015
TI - Atrophoderma vermiculatum.
PMID- 25129016
TI - Non-bullous congenital ichthyosiform erythroderma.
PMID- 25129017
TI - Crusted scabies.
PMID- 25129019
TI - An automatic tool to facilitate the statistical group analysis of DTI.
AB - BACKGROUND: Users may have difficulty calculating DTI group statistics since they
need to master several complex tools that require high user intervention. A tool
called DTIStatistics for the automatic and easy calculation of DTI group
statistics was developed to reduce analysis times and possible errors. METHODS:
The proposed software was designed by using a user-centred methodology in which
we performed an iterative usability evaluation with an expert committee. Once the
experts' requirements were fulfilled, we performed a validation of the final
version of DTIStatistics with target users, comparing the execution time of this
tool and the standard pipeline normally used. RESULTS: Target users needed
significantly less time to complete the tasks with DTIStatistics, reducing the
analysis time from 1383.78 to 57.2s. They were able to complete all the tasks and
barely made errors. Moreover, target users were not able to display the analysis
results with the standard pipeline, but when using our tool they only needed 34s.
Target users found DTIStatistics easy to learn, use and interact with, and they
concluded that they could effectively complete the tasks with it. Additionally,
we present example results in the study of depression to demonstrate the validity
of DTIStatistics for clinical research. CONCLUSIONS: DTIStatistics facilitates
and significantly automates the calculation of DTI group statistics by reducing
the analysis times, which implies lower costs. DTIStatistics is highly applicable
in clinical research, as demonstrated by the fact that it is currently being used
at the University Hospital, University of Navarra (Spain).
PMID- 25129020
TI - Visualizing in vivo brain neural structures using volume rendered feature spaces.
AB - BACKGROUND: Dendrites of cortical neurons are widely spread across several layers
of the cortex. Recently developed two-photon microscopy systems are capable of
visualizing the morphology of neurons within deeper layers of the brain and
generate large amounts of volumetric imaging data from living tissue. METHOD: For
visual exploration of the three-dimensional (3D) structure of dendrites and the
connectivity among neurons in the brain, we propose a visualization software and
interface for 3D images based on a new transfer function design using volume
rendered feature spaces. This software enables the visualization of
multidimensional descriptors of shape and texture extracted from imaging data to
characterize tissue. It also allows the efficient analysis and visualization of
large data sets. RESULTS: We apply and demonstrate the software to two-photon
microscopy images of a living mouse brain. By applying the developed
visualization software and algorithms to two-photon microscope images of the
mouse brain, we identified a set of feature values that distinguish
characteristic structures such as soma, dendrites and apical dendrites in mouse
brain. Also, the visualization interface was compared to conventional 1D/2D
transfer function system. CONCLUSIONS: We have developed a visualization tool and
interface that can represent 3D feature values as textures and shapes. This
visualization system allows the analysis and characterization of the higher
dimensional feature values of living tissues at the micron level and will
contribute to new discoveries in basic biology and clinical medicine.
PMID- 25129021
TI - OvaSpec - A vision-based instrument for assessing concentration and developmental
stage of Trichuris suis parasite egg suspensions.
AB - BACKGROUND: OvaSpec is a new, fully automated, vision-based instrument for
assessing the quantity (concentration) and quality (embryonation percentage) of
Trichuris suis parasite eggs in liquid suspension. The eggs constitute the active
pharmaceutical ingredient in a medicinal drug for the treatment of immune
mediated diseases such as Crohn's disease, ulcerative colitis, and multiple
sclerosis. METHODS: This paper describes the development of an automated
microscopy technology, including methodological challenges and design decisions
of relevance for the future development of comparable vision-based instruments.
Morphological properties are used to distinguish eggs from impurities and two
features of the egg contents under brightfield and darkfield illumination are
used in a statistical classification to distinguish eggs with undifferentiated
contents (non-embryonated eggs) from eggs with fully developed larvae inside
(embryonated eggs). RESULTS: For assessment of the instrument's performance, six
egg suspensions of varying quality were used to generate a dataset of unseen
images. Subsequently, annotation of the detected eggs and impurities revealed a
high agreement with the manual, image-based assessments for both concentration
and embryonation percentage (both error rates <1.0%). Similarly, a strong
correlation was demonstrated in a final, blinded comparison with traditional
microscopic assessments performed by an experienced laboratory technician.
CONCLUSIONS: The present study demonstrates the applicability of computer vision
in the production, analysis, and quality control of T. suis eggs used as an
active pharmaceutical ingredient for the treatment of autoimmune diseases.
PMID- 25129018
TI - A computational pipeline for quantification of mouse myocardial stiffness
parameters.
AB - The mouse is an important model for theoretical-experimental cardiac research,
and biophysically based whole organ models of the mouse heart are now within
reach. However, the passive material properties of mouse myocardium have not been
much studied. We present an experimental setup and associated computational
pipeline to quantify these stiffness properties. A mouse heart was excised and
the left ventricle experimentally inflated from 0 to 1.44kPa in eleven steps, and
the resulting deformation was estimated by echocardiography and speckle tracking.
An in silico counterpart to this experiment was built using finite element
methods and data on ventricular tissue microstructure from diffusion tensor MRI.
This model assumed a hyperelastic, transversely isotropic material law to
describe the force-deformation relationship, and was simulated for many parameter
scenarios, covering the relevant range of parameter space. To identify well
fitting parameter scenarios, we compared experimental and simulated outcomes
across the whole range of pressures, based partly on gross phenotypes (volume,
elastic energy, and short- and long-axis diameter), and partly on node positions
in the geometrical mesh. This identified a narrow region of experimentally
compatible values of the material parameters. Estimation turned out to be more
precise when based on changes in gross phenotypes, compared to the prevailing
practice of using displacements of the material points. We conclude that the
presented experimental setup and computational pipeline is a viable method that
deserves wider application.
PMID- 25129022
TI - Exploring the effects of intervention for those at high risk of developing type 2
diabetes using a computer simulation.
AB - A simulation based computational method was conducted to reflect the effect of
intervention for those at high risk of type 2 diabetes. Hierarchy Support Vector
Machines (H-SVMs) were used to classify high risk. The proportion transitioning
from the high risk state to moderate state, low state or the normal state was
calculated. When Body Mass Index (BMI) decreased by 5% (weight loss 3-5kg), the
proportion of Class A transferring to a lower state was 15-25%, and risk also
appeared reduced for Class B1. In Class C, when cholesterol (CHOL) was decreased
by 2.5% (0.13-0.34mmol/L), 10-25% transitioned to a lower risk state. The method
could help determine risk transition by the adjustment of sensitive risk factors.
This might provide the basis for implementing intervention in cases in a high
risk state.
PMID- 25129023
TI - Finding multivariate outliers in fMRI time-series data.
AB - A fundamental challenge for researchers studying the brain is to explain how
distributed patterns of brain activity relate to a specific representation or
computation. Multivariate techniques are therefore becoming increasingly popular
for pattern localization of functional magnetic resonance imaging (fMRI) data.
The increased power of these techniques can be offset by their susceptibility to
multivariate outliers, a problem not directly encountered when fMRI data are
analyzed in more common univariate analysis techniques. We test how two
algorithms, High Dimensional Blocked Adaptive Computationally Efficient Outlier
Nominators (HD BACON) and Principal Component based Outlier detection (PCOut),
can detect multivariate outliers in high-dimensional fMRI data, in which the
number of variables is larger than the number of observations. We show how these
methods can be applied to individual, voxel time-series to identify outlying
voxels within a region of interest. Finally, we compare these methods with
simulated data to identify which aspects of the data each method is most
sensitive to. Voxels identified by both algorithms were primarily on the edges of
univariate activation clusters and near the boundaries between different tissue
types. Simulation results showed the PCOut outperformed HD BACON, maintaining
both high sensitivity and specificity across a wide range of outlier
contamination percentages. Our results suggest that multivariate analysis of fMRI
can benefit from including multivariate outlier detection as a routine data
quality check prior to model fitting.
PMID- 25129024
TI - Proximity of premolar roots to maxillary sinus: a radiographic survey using cone
beam computed tomography.
AB - INTRODUCTION: The proximity of the roots of the posterior maxillary teeth to the
maxillary sinus is a constant challenge to the dental practitioner. Because the
majority of studies have assessed the relationship regarding molars, the present
study focused on premolars. METHODS: Cone-beam computed tomographic images of 192
patients were reconstructed in sagittal, coronal, and axial planes to quantify
the distances between the root apices of the maxillary premolars and the adjacent
maxillary sinus. Measurements were taken for each root, and data were correlated
with age, sex, side, and presence of both or absence of 1 of the 2 premolars.
RESULTS: A total of 296 teeth (177 first and 119 second premolars) were
evaluated. The mean distances from buccal roots of the first premolars to the
border of the maxillary sinus in the sagittal, coronal, and axial planes ranged
from 5.15 +/- 2.99 to 8.28 +/- 6.27 mm. From palatal roots, the mean distances
ranged from 4.20 +/- 3.69 to 7.17 +/- 6.14 mm. The mean distances of second
premolars were markedly shorter in buccal roots between 2.32 +/- 2.19 and 3.28 +/
3.17 mm and in palatal roots between 2.68 +/- 3.58 and 3.80 +/- 3.71 mm,
respectively. The frequency of a premolar root protrusion into the maxillary
sinus was very low in first premolars (0%-7.2%) but higher in second premolars
(2.5%-13.6%). Sex, age, side, and presence/absence of premolars failed to
significantly influence the mean distances between premolar roots and the
maxillary sinus. CONCLUSIONS: Based on the calculated mean distances of the
present study, only few premolars (and if so second premolars) would present a
risk of violating the border of the maxillary sinus during conventional or
surgical endodontic treatment or in case of tooth extraction.
PMID- 25129026
TI - Assessment of the mechanical properties of ProTaper Next Nickel-titanium rotary
files.
AB - INTRODUCTION: The purpose of this study was to compare the torsional resistance,
flexibility, and surface microhardness of ProTaper Next files (PTN) with Twisted
Files (TF) and RaCe (RC). METHODS: A metal block with a cubical hole was used to
evaluate the torsional resistance. Five millimeters of the tip of each file was
securely held in place by filling the mold with a resin composite, and the files
were driven clockwise at 300 rpm. The number of load applications before fracture
was recorded for each file. A scanning electron microscope was used to
characterize the topographic features of the fracture surfaces of the broken
files. The files were tested for bending resistance by using cantilever-bending
test. Vickers microhardness was measured on the cross section of instruments with
300-g load and 15-second dwell time. Torsional resistance data were analyzed by
using the nonparametric Kruskal-Wallis and Mann-Whitney U tests. Bending
resistance and microhardness data were analyzed by using analysis of variance and
Tukey tests. RESULTS: PTN showed the highest torsional resistance and
microhardness, followed by RC (P < .05). The fracture cross sections of all
brands showed dimpling near the center of fracture surface. The ranking in the
bending resistance values was as follows: RC > PTN > TF. CONCLUSIONS: PTN
improved its resistance to torsional stresses and wear compared with TF and RC.
TF showed improved flexibility compared with other tested brands.
PMID- 25129025
TI - Zinc incorporation improves biological activity of beta-tricalcium silicate resin
based cement.
AB - INTRODUCTION: Matrix metalloproteinase (MMP) inhibition may improve endodontic
treatment prognosis. The purpose of this study was to determine if zinc
incorporation into experimental resin cements containing bioactive fillers may
modulate MMP-mediated collagen degradation of dentin. METHODS: Human dentin
samples untreated and demineralized using 10% phosphoric acid or 0.5 mol/L EDTA
were infiltrated with the following experimental resins: (1) unfilled resin, (2)
resin with Bioglass 45S5 particles (OSspray, London, UK), (3) resin with beta
tricalcium silicate particles (betaTCS), (4) resin with zinc-doped Bioglass 45S5,
and (5) resin with zinc-doped betaTCS particles. The specimens were stored in
artificial saliva (for 24 hours, 1 week, and 4 weeks) and submitted to
radioimmunoassay to quantify C-terminal telopeptide. Scanning electron microscopy
analysis was also undertaken on dentin samples after 4 weeks of storage. RESULTS:
Collagen degradation was prominent both in phosphoric acid and EDTA-treated
dentin. Resin infiltration strongly reduced MMP activity in demineralized dentin.
Resin containing Bioglass 45S5 particles exerted higher and stable protection of
collagen. The presence of zinc in betaTCS particles increases MMP inhibition.
Different mineral precipitation was attained in dentin infiltrated with the resin
cements containing bioactive fillers. CONCLUSIONS: MMP degradation of dentin
collagen is strongly reduced after resin infiltration of dentin. Zinc
incorporation in betaTCS particles exerted an additional protection against MMP
mediated collagen degradation. However, it did not occur in resin containing
Bioglass 45S5 particles, probably because of the formation of phosphate-zinc
compounds.
PMID- 25129027
TI - Psychometric evaluation of the child PTSD symptom scale in Spanish and English.
AB - Given the consistent growth of the Latino population in the United States, there
is a critical need for validated Spanish measures to assess posttraumatic stress
disorder (PTSD) symptoms in children. The current study examines the psychometric
properties of the Child PTSD Symptom Scale (CPSS). We examined 259 children (8-17
years) who had experienced a recent traumatic event. Study measures were
completed in Spanish (n = 106; boys = 58, girls = 48) or in English (n = 153;
boys = 96, girls = 57). In addition to internal consistency, confirmatory factor
analyses were conducted by testing four models to examine construct validity: (1)
PTS single-factor, (2) DSM-IV three-factor, (3) Numbing four-factor, and (4)
Dysphoria four-factor models. Findings demonstrated good internal consistency for
both the English and Spanish versions of the CPSS. The English version revealed
superior fit to the data for several models of PTS symptoms structure compared to
the Spanish version. The current study demonstrated construct validity for the
English CPSS, but not for the Spanish CPSS. Future studies will examine
additional alternative models as well as convergent and discriminant validity of
the Spanish CPSS.
PMID- 25129028
TI - Discovery of a new ATP-binding motif involved in peptidic azoline biosynthesis.
AB - Despite intensive research, the cyclodehydratase responsible for azoline
biogenesis in thiazole/oxazole-modified microcin (TOMM) natural products remains
enigmatic. The collaboration of two proteins, C and D, is required for
cyclodehydration. The C protein is homologous to E1 ubiquitin-activating enzymes,
whereas the D protein is within the YcaO superfamily. Recent studies have
demonstrated that TOMM YcaOs phosphorylate amide carbonyl oxygens to facilitate
azoline formation. Here we report the X-ray crystal structure of an
uncharacterized YcaO from Escherichia coli (Ec-YcaO). Ec-YcaO harbors an
unprecedented fold and ATP-binding motif. This motif is conserved among TOMM
YcaOs and is required for cyclodehydration. Furthermore, we demonstrate that the
C protein regulates substrate binding and catalysis and that the proline-rich C
terminus of the D protein is involved in C protein recognition and catalysis.
This study identifies the YcaO active site and paves the way for the
characterization of the numerous YcaO domains not associated with TOMM
biosynthesis.
PMID- 25129029
TI - Engineered oligosaccharyltransferases with greatly relaxed acceptor-site
specificity.
AB - The Campylobacter jejuni protein glycosylation locus (pgl) encodes machinery for
asparagine-linked (N-linked) glycosylation and serves as the archetype for
bacterial N-linked glycosylation. This machinery has been functionally
transferred into Escherichia coli, enabling convenient mechanistic dissection of
the N-linked glycosylation process in this genetically tractable host. Here we
sought to identify sequence determinants in the oligosaccharyltransferase PglB
that restrict its specificity to only those glycan acceptor sites containing a
negatively charged residue at the -2 position relative to asparagine. This
involved creation of a genetic assay, glycosylation of secreted N-linked acceptor
proteins (glycoSNAP), that facilitates high-throughput screening of
glycophenotypes in E. coli. Using this assay, we isolated several C. jejuni PglB
variants that could glycosylate an array of noncanonical acceptor sequences,
including one in a eukaryotic N-glycoprotein. These results underscore the
utility of glycoSNAP for shedding light on poorly understood aspects of N-linked
glycosylation and for engineering designer N-linked glycosylation biocatalysts.
PMID- 25129031
TI - Characteristics of MPO-ANCA-positive granulomatosis with polyangiitis: a
retrospective multi-center study in Japan.
AB - We studied the clinico-pathological differences among PR3-ANCA-positive
granulomatosis with polyangiitis (PR3-GPA), MPO-ANCA-positive GPA (MPO-GPA) and
microscopic polyangiitis (MPA). ANCA-associated vasculitis (AAV) was classified
using the European Medicines Agency classification. We retrospectively analyzed
38 patients with GPA and 41 with MPA treated in eight hospitals in Japan. Of the
patients with GPA, 17 were positive for MPO-ANCA, and 15 for PR3-ANCA. All
patients with MPA were MPO-ANCA positive. The mean ages of those with MPO-GPA
were 69.6 years old, 10 years older than those with PR3-GPA. The majority (82 %)
of patients with MPO-GPA were woman, a significantly greater proportion than for
PR3-GPA. We also found that ear, nose and throat (ENT), nervous system
involvement were significantly more common in MPO-GPA, but renal function was
less impaired than those with MPA. Both PR3-GPA and MPO-GPA relapsed more
frequently than MPA, but overall survival was significantly better (P < 0.01 and
P < 0.05, respectively). Univariate analysis identified the following factors as
predictors of a poor prognosis: MPA (P < 0.01), pulmonary UIP pattern (P < 0.005)
Cr >= 1.7 mg/dl (P < 0.01) and absence of ENT involvement (P < 0.05), which were
characteristics of MPA. In our cohort, MPO-GPA was most likely to affect older
women and was associated with otitis media, nervous system involvement, mild
renal impairment and more favorable outcome. It is clinically useful to
differentiate MPO-GPA from MPA and PR3-GPA in patients with AAV.
PMID- 25129030
TI - A chemical inhibitor of jasmonate signaling targets JAR1 in Arabidopsis thaliana.
AB - Jasmonates are lipid-derived plant hormones that regulate plant defenses and
numerous developmental processes. Although the biosynthesis and molecular
function of the most active form of the hormone, (+)-7-iso-jasmonoyl-L-isoleucine
(JA-Ile), have been unraveled, it remains poorly understood how the diversity of
bioactive jasmonates regulates such a multitude of plant responses. Bioactive
analogs have been used as chemical tools to interrogate the diverse and dynamic
processes of jasmonate action. By contrast, small molecules impairing jasmonate
functions are currently unknown. Here, we report on jarin-1 as what is to our
knowledge the first small-molecule inhibitor of jasmonate responses that was
identified in a chemical screen using Arabidopsis thaliana. Jarin-1 impairs the
activity of JA-Ile synthetase, thereby preventing the synthesis of the active
hormone, JA-Ile, whereas closely related enzymes are not affected. Thus, jarin-1
may serve as a useful chemical tool in search for missing regulatory components
and further dissection of the complex jasmonate signaling networks.
PMID- 25129032
TI - Association of abuse history with symptom severity and quality of life in
patients with fibromyalgia.
AB - A high prevalence of abuse has been reported in patients with fibromyalgia. We
aimed to examine the association between self-reported abuse history and symptom
severity and quality of life (QOL) in 962 patients with fibromyalgia. All
patients completed the Fibromyalgia Impact Questionnaire (FIQ) and the Short Form
36 health survey (SF-36). Multivariate regression analyses were performed. In
total, 289 patients (30%) reported a history of abuse. Of those who specified
abuse types, 161 patients (59%) reported more than 1 type of abuse (36%
emotional, 32% physical, 25% sexual, and 7% verbal). Patients in the abuse group
were younger and more likely to be female, unemployed, unmarried, and current
smokers compared with patients who reported no abuse. After adjusting for these
differences, abuse history was associated with worse symptoms, as indicated by a
higher FIQ total score (P < .001) and higher FIQ subscale scores in physical
function (P = .001), work missed (P < .001), job ability (P < .001), pain (P =
.02), depression (P < .001), and anxiety (P < .001). Similarly, abuse history was
associated with worse QOL, with lower SF-36 scores in all domains except the
physical component summary. In conclusion, abuse history in patients with
fibromyalgia was associated with worse symptoms and QOL compared with those
patients without abuse history. Future studies are needed to assess whether
additional tailored interventions as part of fibromyalgia treatment are helpful
for patients with a history of abuse.
PMID- 25129033
TI - Ultrasound, anthropometry and bioimpedance: a comparison in predicting fat
deposition in non-alcoholic fatty liver disease.
AB - PURPOSE: The aim of our study was the evaluation of anthropometric measurements
[waist circumference and sagittal abdominal diameter (SAD)] and abdominal
bioelectrical impedance analysis (BIA) (ViScan, TANITA) in comparison to several
abdominal ultrasonographic (US) measurements to estimate visceral fat deposition
and liver steatosis in a population of 105 subjects. METHODS: All 105 patients
underwent a complete anthropometric evaluation, blood sample for the
determination of total cholesterol, HDL cholesterol, triglycerides, glucose,
insulin, high-sensitivity C-reactive protein, BIA and US measurements
(peritoneal, pre-peritoneal, peri-renal, para-renal and peri-hepatic fat
thickness). RESULTS: All the ultrasonographic markers considered in our study are
related to the presence of non-alcoholic fatty liver disease (NAFLD), and so is
true for SAD. Comparing ROC curves, peritoneal fat tissue thickness, SAD and
ViScan visceral index are significantly better than waist circumference in
predicting the presence of NAFLD (AUC 0.79 +/- 0.04; 0.81 +/- 0.05; 0.82 +/- 0.04
vs 0.76 +/- 0.05, respectively). CONCLUSIONS: According to our data, various
methods may be useful in evaluating NAFLD, but only ViScan visceral index, US
peritoneal fat thickness and SAD are better than waist circumference. Among them,
SAD is the most promising, due to its small cost and time consumption.
PMID- 25129035
TI - Anger superiority effect for change detection and change blindness.
AB - In visual search, an angry face in a crowd "pops out" unlike a happy or a neutral
face. This "anger superiority effect" conflicts with views of visual perception
holding that complex stimulus contents cannot be detected without focused top
down attention. Implicit visual processing of threatening changes was studied by
recording event-related potentials (ERPs) using facial stimuli using the change
blindness paradigm, in which conscious change detection is eliminated by
presenting a blank screen before the changes. Already before their conscious
detection, angry faces modulated relatively early emotion sensitive ERPs when
appearing among happy and neutral faces, but happy faces only among neutral, not
angry faces. Conscious change detection was more efficient for angry than happy
faces regardless of background. These findings indicate that the brain can
implicitly extract complex emotional information from facial stimuli, and the
biological relevance of threatening contents can speed up their break up into
visual consciousness.
PMID- 25129036
TI - Complex continuous wavelet coherence for EEG microstates detection in insight and
calm meditation.
AB - Complex continuous wavelet coherence (WTC) can be used for non-stationary
signals, such as electroencephalograms. Areas of the WTC with a coherence higher
than the calculated optimal threshold were obtained, and the sum of their areas
was used as a criterion to differentiate between groups of experienced insight
focused meditators, calm-focused meditators and a control group. This method
demonstrated the highest accuracy for the real WTC parts in the frontal region,
while for the imaginary parts, the highest accuracy was shown for the frontal
occipital pairs of electrodes. In the frontal area, in the broadband frequency,
both types of experienced meditators demonstrated an enlargement of the increased
coherence areas for the real WTC parts. For the imaginary parts unaffected by the
volume conduction and global artefacts, the most significant increase occurred
for the frontal occipital pair of electrodes.
PMID- 25129034
TI - Apoptosis of Purkinje and granular cells of the cerebellum following chronic
ethanol intake.
AB - Ethanol alters motricity, learning, cognition, and cellular metabolism in the
cerebellum. We evaluated the effect of ethanol on apoptosis in Golgi, Purkinje,
and granule cells of the cerebellum in adult rats. There were two groups of 20
rats: a control group that did not consume ethanol and an experimental group of
UChA rats that consumed ethanol at 10% (<2 g ethanol/kg body weight/day). At 120
days old, rats were anesthetized and decapitated, and their cerebella were
collected and fixed. Cerebellar sections were subjected to immunohistochemistry
for terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), caspase
3, X-linked inhibitor of apoptosis protein (XIAP), and insulin-like growth factor
1-receptor (IGF-1R); real-time PCR (RT-PCR) to determine caspase-3, XIAP, and IGF
1R gene expression; and transmission electron microscopy (TEM). We identified
fragmentation of DNA and an increase in caspase-3 protein and XIAP in Purkinje
cells, whereas granule cells exhibited increased caspase-3 and XIAP. IGF-1R
expression was unchanged. There was no significant difference in gene expression
of caspase-3, XIAP, and IGF-1R. There were an increase in lipid droplets, a
reduction in the cellular cytoplasm in electron-dense nuclei, and changes in the
myelin sheath in the cerebellar cortex. In conclusion, our data demonstrated that
ethanol induced apoptosis in the Purkinje and granule cells of the cerebellum of
adult UChA rats.
PMID- 25129037
TI - The cognitive antecedents and motivational consequences of the feeling of being
in the zone.
AB - The feeling of being in the zone (related to "flow") is marked by an elevated yet
effortless sense of concentration. Prior research suggests that feelings of being
in the zone are strongest when the demand posed by a task matches one's level of
ability (i.e., the balance hypothesis). In the present article, we tested this
hypothesis using a novel experimental paradigm. By collecting numerous zone
judgments for each participant, we were able to examine intra-individual sources
of variance that explain why people often feel more or less in-the-zone on the
same task from one moment to the next. The results of two experiments provide
support for what we have termed the balance-plus hypothesis, which posits that
zone experiences are strongest (Experiments 1-2) and have the greatest
motivational force (Experiment 2) when the balance between task demand and
ability is accompanied by positive assessments of one's own performance.
PMID- 25129039
TI - Cellulolytic and xylanolytic potential of high beta-glucosidase-producing
Trichoderma from decaying biomass.
AB - Availability, cost, and efficiency of microbial enzymes for lignocellulose
bioconversion are central to sustainable biomass ethanol technology. Fungi
enriched from decaying biomass and surface soil mixture displayed an array of
strong cellulolytic and xylanolytic activities. Strains SG2 and SG4 produced a
promising array of cellulolytic and xylanolytic enzymes including beta
glucosidase, usually low in cultures of Trichoderma species. Nucleotide sequence
analysis of internal transcribed spacer 2 (ITS2) region of rRNA gene revealed
that strains SG2 and SG4 are closely related to Trichoderma inhamatum,
Trichoderma piluliferum, and Trichoderma aureoviride. Trichoderma sp. SG2 crude
culture supernatant correspondingly displayed as much as 9.84 +/- 1.12, 48.02 +/-
2.53, and 30.10 +/- 1.11 units mL(-1) of cellulase, xylanase, and beta
glucosidase in 30 min assay. Ten times dilution of culture supernatant of strain
SG2 revealed that total activities were about 5.34, 8.45, and 2.05 orders of
magnitude higher than observed in crude culture filtrate for cellulase, xylanase,
and beta-glucosidase, respectively, indicating that more enzymes are present to
contact with substrates in biomass saccharification. In parallel experiments,
Trichoderma species SG2 and SG4 produced more beta-glucosidase than the
industrial strain Trichoderma reesei RUT-C30. Results indicate that strains SG2
and SG4 have potential for low cost in-house production of primary lignocellulose
hydrolyzing enzymes for production of biomass saccharides and biofuel in the
field.
PMID- 25129040
TI - Detergent-compatible bacterial amylases.
AB - Proteases, lipases, amylases, and cellulases are enzymes used in detergent
formulation to improve the detergency. The amylases are specifically supplemented
to the detergent to digest starchy stains. Most of the solid and liquid
detergents that are currently manufactured contain alkaline enzymes. The
advantages of using alkaline enzymes in the detergent formulation are that they
aid in removing tough stains and the process is environmentally friendly since
they reduce the use of toxic detergent ingredients. Amylases active at low
temperature are preferred as the energy consumption gets reduced, and the whole
process becomes cost-effective. Most microbial alkaline amylases are used as
detergent ingredients. Various reviews report on the production, purification,
characterization, and application of amylases in different industry sectors, but
there is no specific review on bacterial or fungal alkaline amylases or detergent
compatible amylases. In this mini-review, an overview on the production and
property studies of the detergent bacterial amylases is given, and the stability
and compatibility of the alkaline bacterial amylases in the presence of the
detergents and the detergent components are highlighted.
PMID- 25129038
TI - Using familial information for variant filtering in high-throughput sequencing
studies.
AB - High-throughput sequencing studies (HTS) have been highly successful in
identifying the genetic causes of human disease, particularly those following
Mendelian inheritance. Many HTS studies to date have been performed without
utilizing available family relationships between samples. Here, we discuss the
many merits and occasional pitfalls of using identity by descent information in
conjunction with HTS studies. These methods are not only applicable to family
studies but are also useful in cohorts of apparently unrelated, 'sporadic' cases
and small families underpowered for linkage and allow inference of relationships
between individuals. Incorporating familial/pedigree information not only
provides powerful filtering options for the extensive variant lists that are
usually produced by HTS but also allows valuable quality control checks, insights
into the genetic model and the genotypic status of individuals of interest. In
particular, these methods are valuable for challenging discovery scenarios in HTS
analysis, such as in the study of populations poorly represented in variant
databases typically used for filtering, and in the case of poor-quality HTS data.
PMID- 25129041
TI - An anisakis larva attached to early gastric cancer: report of a case.
AB - Gastrointestinal anisakidosis is a nematode infection caused by the ingestion of
larvae-infected raw or undercooked fish. The Japanese like to eat raw or
undercooked fish, so gastric anisakiasis is a common disease in Japan. However,
reports of anisakiasis with gastrointestinal cancer are rare. A 63-year-old
Japanese male was diagnosed with a small early gastric cancerous lesion
associated with gastric anisakiasis. From our experience and based on a review of
the literature, the attachment of an anisakis larva to early gastric cancer is
not considered accidental.
PMID- 25129042
TI - DPP6 gene disruption in a family with Gilles de la Tourette syndrome.
AB - Gilles de la Tourette syndrome (TS) is a neurodevelopmental disorder
characterized by multiple motor and vocal tics, frequently associated with
psychiatric co-morbidities. Despite the significant level of heritability, the
genetic architecture of TS still remains elusive. Herein, we investigated an
Italian family where an 8-year-old boy, his father, and paternal uncle have a
diagnosis of TS. Array-CGH and high resolution SNP-array analyses revealed a
heterozygous microdeletion of ~135 kb at the 7q36.2 locus in the proband and his
father. Fluorescent in situ hybridization and quantitative PCR (qPCR) analyses
confirmed the presence of the alteration also in the paternal uncle. The deletion
selectively involves the first exon of the DPP6 gene, leading to a down
regulation of its expression, as demonstrated by the reduced messenger RNA (mRNA)
levels assessed by RT-qPCR. The DPP6 gene encodes for a type II membrane
glycoprotein expressed predominantly in the central nervous system. To date, a de
novo DPP6 exonic duplication, of uncertain significance, was reported in one
patient with TS. Moreover, the DPP6 gene has been implicated in the pathogenesis
of autism spectrum disorder (ASD) and, notably, in haloperidol-induced
dyskinesia. This first familial case provides evidence for association between
DPP6 haploinsufficiency and TS, further suggesting a plausible molecular link
between TS and ASD, and might shed some light on the efficacy and tolerability
profiles of antidopaminergic agents used for tic management, thus prompting
further studies on a larger cohort of patients.
PMID- 25129043
TI - Malignant dysphagia treated by esophageal sparing surgery with good prognosis.
PMID- 25129045
TI - Microbial lipid production: screening with yeasts grown on Brazilian molasses.
AB - Rhodotorula glutinis CCT 2182, Rhodosporidium toruloides CCT 0783, Rhodotorula
minuta CCT 1751 and Lipomyces starkeyi DSM 70296 were evaluated for the
conversion of sugars from Brazilian molasses into single-cell oil (SCO) feedstock
for biodiesel. Pulsed fed-batch fermentations were performed in 1.65 l working
volume bioreactors. The maximum specific growth rate (umax), lipid productivity
(Pr) and cellular lipid content were, respectively, 0.23 h(-1), 0.41 g l(-1) h(
1), and 41% for Rsp. toruloides; 0.20 h(-1), 0.27 g l(-1) h(-1), and 36% for Rta.
glutinis; 0.115 h(-1), 0.135 g l(-1) h(-1), and 27 % for Rta. minuta; and 0.11 h(
1), 0.13 g l(-1) h(-1), and 32% for L. starkeyi. Based on their microbial lipid
productivity, content, and profile, Rsp. toruloides and Rta. glutinis are
promising candidates for biodiesel production from Brazilian molasses. All the
oils from the yeasts were similar to the composition of plant oils (rapeseed and
soybean) and could be used as raw material for biofuels, as well as in food and
nutraceutical products.
PMID- 25129046
TI - Pretreatment with mechano-growth factor E peptide protects bone marrow
mesenchymal cells against damage by fluid shear stress.
AB - Improper fluid shear stress (FSS) can cause serious damages to bone marrow
mesenchymal stem cells (MSCs). Mechano-growth factor (MGF) E peptide pretreatment
was proposed to protect MSCs against FSS damage in this study. MSCs were exposed
to FSS for 30 min after they were pretreated with MGF E peptide for 24 h. Then,
the effects of MGF E peptide on the viability, proliferation and cell apoptosis
of MSCs were investigated. MGF E peptide pretreatment could recover the cellular
metabolic activity of MSCs reduced by 72 dyne cm(-2) FSS and had a synergistic
effect with FSS on the cellular metabolic viability of MSCs under 24 and 72 dyne
cm(-2) FSS. These results suggested that MGF E peptide pretreatment could be an
effective method for the protection of FSS damage in bone tissue engineering.
PMID- 25129044
TI - More than spikes: common oscillatory mechanisms for content specific neural
representations during perception and memory.
AB - Although previous research into the mechanisms underlying sensory and episodic
representations has primarily focused on changes in neural firing rate, more
recent evidence suggests that neural oscillations also contribute to these
representations. Here, we argue that multiplexed oscillatory power and phase
contribute to neural representations at the mesoscopic scale, complementary to
neuronal firing. Reviewing recent studies which used oscillatory activity to
decipher content-specific neural representations, we identify oscillatory
mechanisms common to both sensory and episodic memory representations and
incorporate these into a model of episodic encoding and retrieval. This model
advances the idea that oscillations provide a reference frame for phase-coded
item representations during memory encoding and that shifts in oscillatory
frequency and phase coordinate ensemble activity during memory retrieval.
PMID- 25129047
TI - Regioselective hydroxylation of 17beta-estradiol by mutants of CYP102A1 from
Bacillus megaterium.
AB - A large set of mutants of CYP102A1 from Bacillus megaterium have human cytochrome
P450-like activities and the ability to metabolize a number of marketed drugs and
steroids. Here, we tested whether the CYP102A1 mutants could be used to produce
hydroxylated human metabolites of 17beta-estradiol (E2). A set of the mutants,
which were generated by site-directed and random mutagenesis, was used to produce
hydroxylated human metabolites of E2 in this study. Some of the tested mutants
could regioselectively generate 2-OH E2 as a major metabolite but not other
hydroxylated products. These results suggest that CYP102A1 mutants would be
useful for the bioconversion of steroid hormones to hydroxylated products, which
can be used for industrial applications.
PMID- 25129048
TI - Probing the bioethanol production potential of Scheffersomyces (Pichia) stipitis
using validated genome-scale model.
AB - A detailed in silico analysis of different strategies for enhancement of
bioethanol production by Scheffersomyces stipitis, = Pichia stipitis, using
validated genome-scale metabolic model is presented. Glucose inhibition on xylose
uptake is dominant in S. stipitis which makes fed-batch fermentation more
effective for higher sugar concentrations. Bioethanol production potential of S.
stipitis can be improved by growth media modification by introducing certain
amino acids in small quantities. Slower sugar uptake by S. stipitis can be
overcome by community-culture with recombinant Escherichia coli strain ZSC113,
which has a higher xylose uptake rate. Ethanol yield and productivity of
community-culture can be further enhanced by genetic modification of E. coli
strain ZSC113.
PMID- 25129049
TI - Secretory expression of a bispecific antibody targeting tumor necrosis factor and
ED-B fibronectin in Pichia pastoris and its functional analysis.
AB - Specific targeting of tumor necrosis factor (TNF)-alpha antagonist to the
inflamed site could increase its efficacy and reduce side-effects. Here, we
constructed a bispecific diabody (BsDb) that targets TNF-alpha and ED-B
containing fibronectin, a fibronectin isoform specifically expressed in the
pannus of the inflamed synovium in rheumatoid arthritis. BsDb was secreted from
Pichia pastoris as functional protein and was purified to homogeneity. BsDb could
simultaneously bind to human TNF-alpha and B-FN and neutralize TNF-alpha action.
Additionally, BsDb showed a significant gain both in the antigen-binding affinity
and in TNF-alpha-neutralizing ability as compared to its original antibodies, L19
and anti-TNF-alpha scFv, which were produced in E. coli. BsDb was constructed and
was endowed with enhanced bioactivities and improved production processing.
Therefore, it holds great potential for in vivo applications.
PMID- 25129050
TI - Structural analysis of cerebrosides from Aspergillus fungi: the existence of
galactosylceramide in A. oryzae.
AB - Glucosylceramide and galactosylceramide were detected in three Aspergillus
species: Aspergillus oryzae, Aspergillus sojae and Aspergillus. awamori, using
borate-coated TLC. The cerebrosides from A. oryzae were further purified by ion
exchange and iatrobeads column chromatographies with or without borate, and
determined the composition of sugar, fatty acid and sphingoid base by GC/MS,
MALDI-TOF/MS and (1)H-NMR. We identified them as beta-glucosylceramide and beta
galactosylceramide. The ceramide moiety of both cerebrosides consisted mainly of
2-hydroxystearic acid and either 9-methyl-octadeca-4, 8-sphingadienine or
octadeca-4, 8-sphingadienine. To our knowledge, this is the first study to
provide evidence for the presence of beta-galactosylceramide in A. oryzae.
PMID- 25129051
TI - Comparative effects of technical-grade and a commercial formulation of glyphosate
on the pigment content of periphytic algae.
AB - We investigated the potentially different effects of one of the most commonly
used glyphosate formulations in Argentina, Glifosato Atanor((r)), and the
technical-grade glyphosate on the pigment content, as biomass indicators of the
algal fraction in a freshwater periphytic community. A laboratory bioassay was
carried out in 250-ml beakers. Two treatments were used: technical-grade
glyphosate acid and Glifosato Atanor((r)) (isopropylamine salt of glyphosate 48 %
w/v), which were at a concentration of 3 mg active ingredient per liter.
Treatments and the control (without herbicide) were replicated in triplicate. The
concentrations of chlorophyll a and b and carotenes were determined at 0, 2, 6,
10, 24, 48, 96 and 192 h after herbicide addition. A significant increase in
pigment content was observed for both herbicides after a 2-day exposure.
Moreover, the formulation had little or no effect compared to the active
ingredient, suggesting that the additives of Glifosato Atanor((r)) may not
enhance glyphosate toxicity.
PMID- 25129053
TI - Mechanistic modelling of toxicokinetic processes within Myriophyllum spicatum.
AB - Effects of chemicals are, in most cases, caused by internal concentrations within
organisms which rely on uptake and elimination kinetics. These processes might be
key components for assessing the effects of time-variable exposure of chemicals
which regularly occur in aquatic systems. However, the knowledge of toxicokinetic
patterns caused by time-variable exposure is limited, and gaining such
information is complex. In this work, a previously developed mechanistic growth
model of Myriophyllum spicatum is coupled with a newly developed toxicokinetic
part, providing a model that is able to predict uptake and elimination of
chemicals, as well as distribution processes between plant compartments (leaves,
stems, roots) of M. spicatum. It is shown, that toxicokinetic patterns, at least
for most of the investigated chemicals, can be calculated in agreement with
experimental observations, by only calibrating two chemical- specific parameters,
the cuticular permeability and a plant/water partition coefficient. Through the
model-based determination of the cuticular permeabilities of Isoproturon,
Iofensulfuron, Fluridone, Imazamox and Penoxsulam, their toxicokinetic pattern
can be described with the model approach. For the use of the model for predicting
toxicokinetics of other chemicals, where experimental data is not available,
equations are presented that are based on the log (P oct/wat) of a chemical and
estimate parameters that are necessary to run the model. In general, a method is
presented to analyze time-variable exposure of chemicals more in detail without
conducting time and labour intensive experiments.
PMID- 25129052
TI - Epidemiology of MPN: what do we know?
AB - The myeloproliferative neoplasms, are characterised by overproduction of myeloid
cells. Chronic myeloid leukaemia, polycythaemia vera, essential thrombocythaemia,
myelofibrosis and the very rare disorders chronic neutrophilic leukaemia, chronic
eosinophilic leukaemia not otherwise specified and mastocytosis are all included
in the group. Incidence and prevalence rates reported in the worldwide literature
are presented in this review. Survival data on each condition is described.
Information on the aetiology of the disorders is discussed including body mass
index, diet, smoking and alcohol, allergies, associated medical conditions,
occupation and environmental exposures with focus on recent new studies. The
aetiology of the myeloproliferative neoplasms remains unknown, and this review of
the current state of knowledge highlights the need for further comprehensive
research.
PMID- 25129054
TI - The use of the EQ-5D as a measure of health-related quality of life in people
with dementia and their carers.
AB - PURPOSE: To assess the acceptability, validity and inter-rater agreement of self-
and family carer proxy ratings of the EQ-5D as a generic health-related quality
of life (HRQOL) measure, in people with mild to moderate dementia (PwD) living in
the community. A secondary aim was to identify the most important factors
influencing self- and family carer proxy ratings of HRQOL, distinguishing between
spouse and adult child caregiver ratings. METHODS: Cross-sectional study of 488
dyads using the EQ-5D. Inter-rater agreement was examined using weighted kappa
scores, and validity by investigating the association of self- and family carer
ratings with clinical variables. Factors affecting HRQOL ratings were analysed
using multivariate regression. RESULTS: The response rate of the EQ-5D was
satisfactory; however, agreement between self- and family carer ratings was poor.
The most important predictors of PwD and carer ratings of the PwD's HRQOL were
family carer ratings of activities of daily living and mood. Anxiety experienced
by the PwD was a significant predictor of self-rated HRQOL, whereas depressive
symptoms independently predicted family carer ratings. The type of the caregiving
relationship influenced carer ratings of HRQOL, whereby sons and daughters rated
HRQOL lower for the PwD compared with spousal caregivers. CONCLUSIONS: People
with mild to moderate dementia are able to rate their own HRQOL through a brief
generic instrument; however, self-ratings consistently differ from family carer
ratings, which should be acknowledged in cost-effectiveness analyses. Spouse
caregivers rate HRQOL for the PwD more positively compared to adult children.
PMID- 25129055
TI - Ligand-directed tosyl chemistry for in situ native protein labeling and
engineering in living systems: from basic properties to applications.
AB - The ability to introduce any chemical probe to any endogenous target protein in
its native environment, that is in cells and in vivo, is anticipated to provide
various new exciting tools for biological and biomedical research. Although still
at the prototype stage, the ligand-directed tosyl (LDT) chemistry is a novel type
of affinity labeling technique that we developed for such a dream. This chemistry
allows for modifying native proteins by various chemical probes with high
specificity in various biological settings ranging from in vitro (in test tubes)
to in living cells and in vivo. Since the first report, the list of proteins that
are successfully labeled by the LDT chemistry has been increasing. A growing
number of studies have demonstrated its utility to create semisynthetic proteins
directly in cellular contexts. The in situ generated semisynthetic proteins are
applicable for various types of analysis and imaging of intracellular biological
processes. In this review, we summarize the basic properties of the LDT chemistry
and its applications toward in situ engineering and analysis of native proteins
in living systems. Current limitations and future challenges of this area are
also described.
PMID- 25129056
TI - Turning the spotlight on protein-lipid interactions in cells.
AB - Protein function is largely dependent on coordinated and dynamic interactions of
the protein with biomolecules including other proteins, nucleic acids and lipids.
Although powerful methods for global profiling of protein-protein and protein
nucleic acid interactions are available, proteome-wide mapping of protein-lipid
interactions is still challenging and rarely performed. The emergence of
bifunctional lipid probes with photoactivatable and clickable groups offers new
chemical tools for globally profiling protein-lipid interactions under cellular
contexts. In this review, we summarize recent advances in the development of
bifunctional lipid probes for studying protein-lipid interactions. We also
highlight how in vivo photocrosslinking reactions contribute to the
characterization of lipid-binding proteins and lipidation-mediated protein
protein interactions.
PMID- 25129057
TI - The role of mitochondrial reactive oxygen species in cartilage matrix
destruction.
AB - Upregulation of matrix metalloproteinases (MMPs) is a hallmark of osteoarthritis
progression; along with the role reactive oxygen species (ROS) may play in this
process. Moreover, mitochondrial DNA damage and dysfunction are also present in
osteoarthritic chondrocytes. However, there are no studies published
investigating the direct relationship between mitochondrial ROS, mitochondrial
DNA damage, and MMP expression. Therefore, the purpose of the present study was
to evaluate whether mitochondrial DNA damage and mitochondrial-originated
oxidative stress modulates matrix destruction through the upregulation of MMP
protein levels. MitoSox red was utilized to observe mitochondrial ROS production
while a Quantitative Southern blot technique was conducted to analyze
mitochondrial DNA damage. Additionally, Western blot analysis was used to
determine MMP protein levels. The results of the present study show that
menadione augmented mitochondrial-generated ROS and increased mitochondrial DNA
damage. This increase in mitochondrial-generated ROS led to an increase in MMP
levels. When a mitochondrial ROS scavenger was added, there was a subsequent
reduction in MMP levels. These studies reveal that mitochondrial integrity is
essential for maintaining the cartilage matrix by altering MMP levels. This
provides new and important insights into the role of mitochondria in chondrocyte
function and its potential importance in therapeutic approaches.
PMID- 25129058
TI - Pemetrexed ameliorates experimental arthritis in rats.
AB - Pemetrexed (PMTX) is an anti-folate drug as methotrexate. The purpose of this
study was to assess the efficacy of PMTX on collagen-induced arthritis (CIA).
Forty Wistar albino rats were randomized into four groups. Arthritis was induced
by intradermal injection of chicken type II collagen combined with incomplete
Freund's adjuvant. Animals were sacrificed at the 15th day after the onset of
arthritis. Tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-17, and
malondialdehyde (MDA) levels were increased, and superoxide dismutase (SOD),
catalase (CAT), and glutathione peroxidase (GPx) activities and the expressions
of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1)
were decreased in the arthritis group. In the PMTX-treated (0.2 and 1 mg/kg/week
i.p.) groups, the levels of TNF-alpha, IL-17, and MDA were decreased; the
activities of SOD, CAT, and GPx and the expressions of Nrf2 and HO-1 were
restored, and perisynovial inflammation and cartilage-bone destruction were
decreased. PMTX has anti-arthritic potential in the CIA model and may be a
therapeutic agent for rheumatoid arthritis.
PMID- 25129059
TI - Expression of CXCR1 (interleukin-8 receptor) in murine macrophages after
staphylococcus aureus infection and its possible implication on intracellular
survival correlating with cytokines and bacterial anti-oxidant enzymes.
AB - Interaction with the live Staphylococcus aureus promotes secretion of interleukin
8 (IL-8), although the expressions of functional CXCR1 (IL-8RA) in murine
macrophages have not been identified. Expression of CXCR1 was induced in S.
aureus-infected macrophages, whereas, CXCR1 was undetectable in control
macrophages. CXCR1 blocking significantly reduced the phagocytosis of S. aureus
and TNF-alpha, IL-6, IL-1beta, IFN-gamma, IL-12, and IL-8 production and
increased release of MIP-2 and soluble TNF-R1. Increased bacterial catalase and
decreased superoxide dismutase (SOD) activities by S. aureus with concomitant
decrease in hydrogen peroxide (H2O2), superoxide anion, and nitric oxide (NO)
release were observed in case of prior CXCR1 blocking. In the presence of
cytochalasin D, S. aureus-mediated induction of IL-8 was inhibited concomitant
with decreased bacterial count suggesting that internalization of S. aureus was
necessary for induction of IL-8. Shedding of TNF-R1 due to CXCR1 blocking after
S. aureus inoculation was critical for neutralization of TNF-alpha signaling and
arrests the inflammation.
PMID- 25129061
TI - Separation of cis- and trans-cypermethrin by reversed-phase high-performance
liquid chromatography.
AB - As a pyrethroid insecticide, cypermethrin (CP) possesses three chiral centers and
thus consists of eight optical isomers. High-performance liquid chromatography
(HPLC) methods have been established for the separation and determination of
pyrethroid insecticides. In this article, we report a new reversed-phase high
performance liquid chromatography (RP-HPLC) method of separating the
diastereomers of CP. Our method was performed on a C18 column with the following
specifications: mobile phase, methanol/acetonitrile/water (58:18:24, v/v/v); flow
rate, 1.0 mL/min; column temperature, 20 degrees C and UV-detection wavelength,
235 nm. The results showed that the applied procedure was linear based on
calibration curves with equation (y = 16.595x + 1.7892) within the CP
concentration range of 5-100 mg/L. The limit of detection and limit of
quantification of CP were 0.2 and 0.7 mg/L, respectively. CP or beta-CP extracted
from the microbial degradation system was determined, and the method was proved
to be accurate and applicable. Therefore, the proposed RP-HPLC method was simple,
inexpensive and can be used to study stability and determine CP residues in
pharmaceutical preparations or in the environment.
PMID- 25129060
TI - CD86 polymorphism affects pneumonia-induced sepsis by decreasing gene expression
in monocytes.
AB - Sepsis, a clinical syndrome occurring in patients following infection or injury,
is a leading cause of morbidity and mortality worldwide. CD86 (B7-2) is a
costimulatory molecule on antigen-presenting cells and plays critical roles in
immune responses. In the current study, we investigated the association of two
CD86 polymorphisms, rs1129055G/A and rs17281995G/C, with susceptibility to
pneumonia-induced sepsis and examined the effects of these two polymorphisms on
gene expression in monocytes. CD86 rs1129055G/A and rs17281995G/C were identified
in 192 pneumonia-induced septic patients and 201 healthy controls. Data showed
that frequencies of the rs1129055GA and AA genotypes were significantly lower in
patients than in controls (odds ratio [OR]=0.57, 95 % confidence interval [CI],
0.35-0.93, p=0.023, and OR=0.40, 95 % CI, 0.23-0.71, p=0.002). Interestingly, the
other polymorphism, rs17281995G/C, revealed significantly increased numbers in
pneumonia-induced sepsis compared to controls (OR=1.85, 95 % CI, 1.07-3.20,
p=0.025). Further analyses about CD86 gene expression revealed that both
messenger RNA (mRNA) and protein levels of CD86 were downregulated in monocytes
from controls carrying rs17281995GC genotype than those carrying wild-type
rs17281995GG genotype (p=0.022 and p=0013). These results suggest that
polymorphisms in CD86 gene have diverse effects on the pathogenesis of pneumonia
induced sepsis, in which rs17281995G/C may increase the risk of the disease by
interfering gene expression of CD86 in monocytes.
PMID- 25129062
TI - Validation of an HPLC-MS/MS and wipe procedure for mitomycin C contamination.
AB - A high-performance liquid chromatography-tandem mass spectrometric (HPLC-MS/MS)
method was developed for the determination of mitomycin C, an anticancer drug,
from contamination on various surfaces. Mitomycin C is often used in various
forms of intraperitoneal chemotherapy, and operating room healthcare worker
exposure to this drug is possible. The surface testing method consisted of a
wiping procedure utilizing a solution of 20/45/35 (v/v/v) of acetonitrile
isopropanol-water made 0.01 M in ammonium citrate (apparent pH 7.0). The wipe
solutions were analyzed by means of HPLC-MS/MS using a reversed-phase gradient
system and electrospray ionization in positive ion mode with a triple-quadrupole
MS detector. Accuracy and precision of this method were demonstrated by a series
of recovery studies of both spiked solutions and extracted wipes from various
surfaces (stainless steel, vinyl and Formica((r))) spiked with known levels of
mitomycin C. Recoveries of spiked solutions containing the analyte demonstrate
mean recoveries (accuracy) ranged from 93 to 105%. Precision as measured by the
relative standard deviation (% RSD) of multiple samples (n= 10) at each
concentration level demonstrated values of 7.5% or less. The recoveries from
spiked surfaces varied from 30 to 99%. The limit of detection for this
methodology is ~2 ng/100 cm(2) equivalent surface area, and the limit of
quantitation is ~6 ng/100 cm(2).
PMID- 25129063
TI - Discovery of common sequences absent in the human reference genome using pooled
samples from next generation sequencing.
AB - BACKGROUND: Sequences up to several megabases in length have been found to be
present in individual genomes but absent in the human reference genome. These
sequences may be common in populations, and their absence in the reference genome
may indicate rare variants in the genomes of individuals who served as donors for
the human genome project. As the reference genome is used in probe design for
microarray technology and mapping short reads in next generation sequencing
(NGS), this missing sequence could be a source of bias in functional genomic
studies and variant analysis. One End Anchor (OEA) and/or orphan reads from
paired-end sequencing have been used to identify novel sequences that are absent
in reference genome. However, there is no study to investigate the distribution,
evolution and functionality of those sequences in human populations. RESULTS: To
systematically identify and study the missing common sequences (micSeqs), we
extended the previous method by pooling OEA reads from large number of
individuals and applying strict filtering methods to remove false sequences. The
pipeline was applied to data from phase 1 of the 1000 Genomes Project. We
identified 309 micSeqs that are present in at least 1% of the human population,
but absent in the reference genome. We confirmed 76% of these 309 micSeqs by
comparison to other primate genomes, individual human genomes, and gene
expression data. Furthermore, we randomly selected fifteen micSeqs and confirmed
their presence using PCR validation in 38 additional individuals. Functional
analysis using published RNA-seq and ChIP-seq data showed that eleven micSeqs are
highly expressed in human brain and three micSeqs contain transcription factor
(TF) binding regions, suggesting they are functional elements. In addition, the
identified micSeqs are absent in non-primates and show dynamic acquisition during
primate evolution culminating with most micSeqs being present in Africans,
suggesting some micSeqs may be important sources of human diversity. CONCLUSIONS:
76% of micSeqs were confirmed by a comparative genomics approach. Fourteen
micSeqs are expressed in human brain or contain TF binding regions. Some micSeqs
are primate-specific, conserved and may play a role in the evolution of primates.
PMID- 25129064
TI - Usefulness and safety of vorapaxar in patients with non-ST-segment elevation
acute coronary syndrome undergoing percutaneous coronary intervention (from the
TRACER Trial).
AB - The therapeutic potential of vorapaxar in patients with non-ST-segment elevation
acute coronary syndrome undergoing percutaneous coronary intervention (PCI) is
unknown. This prespecified analysis of a postrandomization subgroup evaluated the
effects of vorapaxar compared with placebo among Thrombin Receptor Antagonist for
Clinical Event Reduction in Acute Coronary Syndrome (TRACER) participants
undergoing PCI, focusing on the implanted stent type (drug-eluting stent [DES] vs
bare-metal stent [BMS]). Among 12,944 recruited patients, 7,479 (57.8%) underwent
PCI during index hospitalization, and 3,060 (40.9%) of those patients received
exclusively BMS, whereas 4,015 (53.7%) received DES. The median (twenty-fifth,
seventy-fifth percentiles) duration of thienopyridine therapy was 133 days (47,
246) with BMS and 221 days (88, 341) with DES. At 2 years among patients
undergoing PCI, the primary (cardiovascular death, myocardial infarction, stroke,
recurrent ischemia with rehospitalization, or urgent coronary revascularization)
and secondary (cardiovascular death, myocardial infarction, or stroke) end points
did not differ between vorapaxar and placebo groups, which was consistent with
the treatment effect observed in the overall study population (p value for
interaction = 0.540). However, the treatment effect trended greater (p value for
interaction = 0.069) and the risk for bleeding in patients taking vorapaxar
versus placebo appeared attenuated in BMS-only recipients. After adjustment for
confounders, the interaction was no longer significant (p value = 0.301). The
covariate that mostly explained the stent-type-by-treatment interaction was the
duration of clopidogrel therapy. In conclusion, among patients with PCI, the
effect of vorapaxar is consistent with the overall TRACER results. Patients who
received a BMS underwent shorter courses of clopidogrel therapy and displayed
trends toward greater ischemic benefit from vorapaxar and lesser bleeding risk,
compared with patients who received a DES.
PMID- 25129065
TI - Comparison of safety of sotalol versus amiodarone in patients with atrial
fibrillation and coronary artery disease.
AB - Sotalol is a commonly prescribed antiarrhythmic drug (AAD) used for maintaining
sinus rhythm in patients with atrial fibrillation (AF). Although randomized
studies have found that sotalol can significantly delay time to AF recurrence,
its association with mortality is less clear, particularly among those with
coronary artery disease. We examined outcomes of 2,838 patients with coronary
artery disease and AF. Using Cox proportional hazards modeling, landmark
analysis, and time-dependent covariates for drug therapy, we compared cumulative
survival among patients treated with sotalol (n = 226), amiodarone (n = 856), or
no AAD (n = 1,756). Median follow-up was 4.2 years (interquartile range [IQR] 2.0
7.4). The median age was 68 years (IQR 60-75). Compared with those treated with
amiodarone or no AAD, patients treated with sotalol were less likely to be black
(6% vs 13% vs 13%) and have a previous myocardial infarction (35% vs 51% vs 48%)
or a left ventricular ejection fraction <40% (13% vs 26% vs 21%). In follow-up,
persistence of sotalol was limited; 97% of patients treated with sotalol were
treated for <25% of the follow-up period. In adjusted analysis accounting for
time on therapy, sotalol use was associated with an increased risk of all-cause
death compared with no drug (hazard ratio 1.53, 95% confidence interval 1.19 to
1.96, p = 0.0009), but a decreased risk of death compared with amiodarone (hazard
ratio 0.72, 95% confidence interval 0.55 to 0.91, p = 0.0141). In conclusion,
sotalol therapy was more frequently used in patients with fewer co-morbidities,
often discontinued early in follow-up, and was associated with increased
mortality compared with no AAD but decreased mortality relative to amiodarone.
PMID- 25129066
TI - Effect of spironolactone on 30-day death and heart failure rehospitalization
(from the COACH Study).
AB - The aim of our study is to investigate the effect of spironolactone on 30-day
outcomes in patients with acute heart failure (AHF) and the association between
treatment and outcomes stratified by biomarkers. We conducted a secondary
analysis of the biomarker substudy of the multicenter COACH (Co-ordinating Study
Evaluating Outcomes of Advising and Counseling in Heart Failure) trial involving
534 AHF patients for 30-day mortality and HF rehospitalizations. Spironolactone
therapy was initiated and terminated at the discretion of the treating physician;
30-day outcomes were compared between patients who were treated with
spironolactone and those who were not. Outcomes with spironolactone therapy were
explored based on N-terminal pro-B-type natriuretic peptide, ST2, galectin-3, and
creatinine levels. Spironolactone was prescribed to 297 (55.6%) patients at
discharge (158 new and 139 continued). There were 19 deaths and 30 HF
rehospitalizations among 46 patients by 30 days. Patients discharged on
spironolactone had significantly less 30-day event (hazard ratio 0.538, p =
0.039) after adjustment for multiple risk factors. Initiation of spironolactone
in patients who were not on spironolactone before admission was associated with a
significant reduction in event rate (hazard ratio 0.362, p = 0.027). The survival
benefit of spironolactone was more prominent in patient groups with elevations of
creatinine, N-terminal pro-B-type natriuretic peptide, ST2, or galectin-3. In
conclusion, AHF patients who received spironolactone during hospitalization had
significantly fewer 30-day mortality and HF rehospitalizations, especially in
high-risk patients.
PMID- 25129067
TI - Prevalence, clinical correlates, and functional impact of subaortic ventricular
septal bulge (from the Baltimore Longitudinal Study of Aging).
AB - A localized hypertrophy of the subaortic segment of the ventricular septum
ventricular septal bulge (VSB)-has been frequently described in series of elderly
population, but its prevalence with age, clinical correlates, and impact on
cardiac function and exercise capacity remain uncertain. We explored these
associations in a cross-sectional sample without known cardiac disease from the
Baltimore Longitudinal Study of Aging. We randomly selected 700 participants (50%
men, mean age 64 +/- 15, range 26 to 95 years) and reviewed their
echocardiograms. We identified 28 men and 21 women with VSB (7% overall
prevalence). The prevalence of VSB significantly increased with age in both
genders (p <0.0001). In multivariate logistic regression including hypertension
and other cardiovascular risk factors, only age displayed a significant
independent association with VSB (OR 1.06 per year, 95% confidence interval 1.03
to 1.10, p = 0.0001). After multiple adjustments, participants with VSB compared
with those without had enhanced global left ventricular contractility (fractional
shortening 41 +/- 1.3 vs 38 +/- 0.3%, p = 0.04; ejection fraction 71 +/- 1.6 vs
67 +/- 0.4%, p = 0.06; systolic velocity of the mitral annulus 8.4 +/- 0.1 vs 8.9
+/- 0.3, p = 0.06), and larger aortic root diameters (3.3 +/- 0.06 vs 3.1 +/-
0.02 cm, p = 0.02). In subgroup of participants who completed a maximal treadmill
test (177 women and 196 men), those with VSB (19, 5.1%) had significantly lower
peak oxygen consumption than their counterparts (19.6 +/- 3.8 vs 22.9 +/- 6.6
ml/kg/min, p = 0.03). However, this association was no longer significant after
multiple adjustments. In conclusion, the presence of VSB is independently
associated with older age and determines enhanced left ventricular contractility,
without any evident impact on exercise capacity.
PMID- 25129068
TI - Polysaccharopeptide enhanced the anti-cancer effect of gamma-tocotrienol through
activation of AMPK.
AB - BACKGROUND: Prostate cancer (PCa) frequently relapses after hormone ablation
therapy. Unfortunately, once progressed to the castration resistant stage, the
disease is regarded as incurable as prostate cancer cells are highly resistant to
conventional chemotherapy. METHOD: We recently reported that the two natural
compounds polysaccharopeptide (PSP) and Gamma-tocotrienols (gamma-T3) possessed
potent anti-cancer activities through targeting of CSCs. In the present study,
using both prostate cancer cell line and xenograft models, we seek to investigate
the therapeutic potential of combining gamma-T3 and PSP in the treatment of
prostate cancer. RESULT: We showed that in the presence of PSP, gamma-T3
treatment induce a drastic activation of AMP-activated protein kinase (AMPK).
This was accompanied with inactivation of acetyl-CoA carboxylase (ACC), as
evidenced by the increased phosphorylation levels at Ser 79. In addition, PSP
treatment also sensitized cancer cells toward gamma-T3-induced cytotoxicity.
Furthermore, we demonstrated for the first time that combination of PSP and gamma
T3 treaments significantly reduced the growth of prostate tumor in vivo.
CONCLUSION: Our results indicate that PSP and gamma-T3 treaments may have
synergistic anti-cancer effect in vitro and in vivo, which warrants further
investigation as a potential combination therapy for the treatment of cancer.
PMID- 25129069
TI - Audit-identified avoidable factors in maternal and perinatal deaths in low
resource settings: a systematic review.
AB - BACKGROUND: Audits provide a rational framework for quality improvement by
systematically assessing clinical practices against accepted standards with the
aim to develop recommendations and interventions that target modifiable
deficiencies in care. Most childbirth-associated mortality audits in developing
countries are focused on a single facility and, up to now, the avoidable factors
in maternal and perinatal deaths cataloged in these reports have not been pooled
and analyzed. We sought to identity the most frequent avoidable factors in
childbirth-related deaths globally through a systematic review of all published
mortality audits in low and lower-middle income countries. METHODS: We performed
a systematic review of published literature from 1965 to November 2011 in Pubmed,
Embase, CINAHL, POPLINE, LILACS and African Index Medicus. Inclusion criteria
were audits from low and lower-middle income countries that identified at least
one avoidable factor in maternal or perinatal mortality. Each study included in
the analysis was assigned a quality score using a previously published
instrument. A meta-analysis was performed for each avoidable factor taking into
account the sample sizes and quality score from each individual audit. The study
was conducted and reported according to PRISMA guidelines for systematic reviews.
RESULTS: Thirty-nine studies comprising 44 datasets and a total of 6,205 audited
deaths met inclusion criteria. The analysis yielded 42 different avoidable
factors, which fell into four categories: health worker-oriented factors, patient
oriented factors, transport/referral factors, and administrative/supply factors.
The top three factors by attributable deaths were substandard care by a health
worker, patient delay, and deficiencies in blood transfusion capacity (accounting
for 688, 665, and 634 deaths attributable, respectively). Health worker-oriented
factors accounted for two-thirds of the avoidable factors identified.
CONCLUSIONS: Audits provide insight into where systematic deficiencies in
clinical care occur and can therefore provide crucial direction for the targeting
of interventions to mitigate or eliminate health system failures. Given that the
main causes of maternal and perinatal deaths are generally consistent across low
resource settings, the specific avoidable factors identified in this review can
help to inform the rational design of health systems with the aim of achieving
continued progress towards Millennium Development Goals Four and Five.
PMID- 25129070
TI - The relationship between the cranial base and jaw base in a Chinese population.
AB - INTRODUCTION: The cranial base plays an important role in determining how the
mandible and maxilla relate to each other. This study assessed the relationship
between the cranial base and jaw base in a Chinese population. METHODS: This
study involved 83 subjects (male: 27; female: 56; age: 18.4+/-4.2 SD years) from
Hong Kong, who were classified into 3 sagittal discrepancy groups on the basis of
their ANB angle. A cephalometric analysis of the angular and linear measurements
of their cranial and jaw bases was carried out. The morphological characteristics
of the cranial and jaw bases in the three groups were compared and assessments
were made as to whether a relationship existed between the cranial base and the
jaw base discrepancy. RESULTS: Significant differences were found in the cranial
base angles of the three groups. Skeletal Class II cases presented with a larger
NSBa, whereas skeletal Class III cases presented with a smaller NSBa (P<0.001).
In the linear measurement, skeletal Class III cases presented with a shorter NBa
than skeletal Class I and II cases (P<0.01). There was a correlation between the
cranial base angle NSBa and the SNB for the whole sample, (r=-0.523, P<0.001).
Furthermore, correlations between SBaFH and Wits (r=-0.594, P<0.001) and SBaFH
and maxillary length (r=-0.616, P<0.001) were more obvious in the skeletal Class
III cases. CONCLUSIONS: The cranial base appears to have a certain correlation
with the jaw base relationship in a southern Chinese population. The correlation
between cranial base and jaw base tends to be closer in skeletal Class III cases.
PMID- 25129071
TI - Age-related change in sit-to-stand power in Japanese women aged 50 years or
older.
AB - BACKGROUND: This study examined whether the age-related change in power,
calculated from the score of a sit-to-stand (STS) test, corresponds to those in
knee extension torque and leg lean tissue mass in Japanese women aged 50 years or
older. FINDINGS: Time for a 10-times-repeated STS test and knee extension torque
were determined in 556 Japanese women aged 50 to 94 years. STS power was
calculated using an equation reported previously. In addition, leg lean tissue
mass was estimated using muscle thicknesses determined at thigh and lower leg.
STS power, knee extension torque, and lean tissue mass were negatively correlated
to age. STS power and knee extension torque, expressed as the percentages of the
mean value of the corresponding variable for the subjects aged 50 to 54 years
were lower than that of lean tissue mass in the subjects aged 60 years or over,
and were similar in those aged under 75 years. However, the relative value of STS
power was lower than that of knee extension torque in the subjects aged over 75
years. CONCLUSIONS: In Japanese women aged 50 to 74 years, STS power can be a
convenient measure for assessing the age-related decline in knee extension
torque, but not for leg lean tissue mass. At over 75 years old, the magnitude of
the age-related decline in STS power does not parallel to that in the force
generation capability of knee extensor muscles.
PMID- 25129072
TI - Freezing and thawing of artificial ice by thermal switching of geometric
frustration in magnetic flux lattices.
AB - The problem of an ensemble of repulsive particles on a potential-energy landscape
is common to many physical systems and has been studied in multiple artificial
playgrounds. However, the latter usually involve fixed energy landscapes, thereby
impeding in situ investigations of the particles' collective response to
controlled changes in the landscape geometry. Here, we experimentally realize a
system in which the geometry of the potential-energy landscape can be switched
using temperature as the control knob. This realization is based on a high
temperature superconductor in which we engineer a nanoscale spatial modulation of
the superconducting condensate. Depending on the temperature, the flux quanta
induced by an applied magnetic field see either a geometrically frustrated energy
landscape that favours an ice-like flux ordering, or an unfrustrated landscape
that yields a periodic flux distribution. This effect is reflected in a dramatic
change in the superconductor's magneto-transport. The thermal switching of the
energy landscape geometry opens new opportunities for the study of ordering and
reorganization in repulsive particle manifolds.
PMID- 25129073
TI - Biocomputing based on particle disassembly.
AB - Nanoparticles with biocomputing capabilities could potentially be used to create
sophisticated robotic devices with a variety of biomedical applications,
including intelligent sensors and theranostic agents. DNA/RNA-based computing
techniques have already been developed that can offer a complete set of Boolean
logic functions and have been used, for example, to analyse cells and deliver
molecular payloads. However, the computing potential of particle-based systems
remains relatively unexplored. Here, we show that almost any type of nanoparticle
or microparticle can be transformed into autonomous biocomputing structures that
are capable of implementing a functionally complete set of Boolean logic gates
(YES, NOT, AND and OR) and binding to a target as result of a computation. The
logic-gating functionality is incorporated into self-assembled
particle/biomolecule interfaces (demonstrated here with proteins) and the logic
gating is achieved through input-induced disassembly of the structures. To
illustrate the capabilities of the approach, we show that the structures can be
used for logic-gated cell targeting and advanced immunoassays.
PMID- 25129074
TI - Exposure to L-cycloserine incurs survival costs and behavioral alterations in
Aedes aegypti females.
AB - BACKGROUND: It was previously demonstrated that alanine aminotransferase (ALAT,
EC 2.6.1.2) participates in maintaining the alanine-proline cycle between flight
muscles and fat body during Aedes aegypti flight. ALAT is also actively involved
in the metabolism of ammonia in A. aegypti. Here, we investigated the survival
and behavioral costs of ALAT inhibition in A. aegypti females to better
understand the role of ALAT in blood-fed mosquitoes. METHODS: We analyzed how A.
aegypti female mosquitoes respond to blood meals supplemented with 0, 2.5, 5 and
10 mM L-cycloserine, a well-known inhibitor of ALAT in animals. Mosquitoes were
also exposed to blood meals supplemented with L-cycloserine and different
concentrations of glucose (0, 10 and 100 mM). Additionally, the effects of ALAT
inhibitor and glucose in mosquitoes starved for 24 or 48 h were investigated.
Survival and behavioral phenotypes were analyzed during a time course (1, 2, 4,
6, 12, 24, 48 and 72 h after feeding). RESULTS: L-cycloserine at 10 mM resulted
in high mortality relative to control, with an acute effect during the first 6 h
after treatment. A significant decrease in the number of active mosquitoes
coinciding with an increase in futile wing fanning during the first 24 h was
observed at all inhibitor concentrations. A high occurrence of knockdown
phenotype was also recorded at this time for both 5 and 10 mM L-cycloserine. The
supplementation of glucose in the blood meal amplified the effects of the ALAT
inhibitor. In particular, we observed a higher mortality rate concomitant with an
increase in the knockdown phenotype. Starvation prior to blood feeding also
increased the effects of L-cycloserine with a rapid increase in mortality.
CONCLUSIONS: Our results provide evidence that exposure of high doses of L
cycloserine during A. aegypti blood feeding affects mosquito survival and motor
activity, suggesting an interference with carbohydrate and ammonia metabolism in
a time-dependent manner.
PMID- 25129076
TI - Hippocampal-neocortical functional reorganization underlies children's cognitive
development.
AB - The importance of the hippocampal system for rapid learning and memory is well
recognized, but its contributions to a cardinal feature of children's cognitive
development-the transition from procedure-based to memory-based problem-solving
strategies-are unknown. Here we show that the hippocampal system is pivotal to
this strategic transition. Longitudinal functional magnetic resonance imaging
(fMRI) in 7-9-year-old children revealed that the transition from use of counting
to memory-based retrieval parallels increased hippocampal and decreased
prefrontal-parietal engagement during arithmetic problem solving. Longitudinal
improvements in retrieval-strategy use were predicted by increased hippocampal
neocortical functional connectivity. Beyond childhood, retrieval-strategy use
continued to improve through adolescence into adulthood and was associated with
decreased activation but more stable interproblem representations in the
hippocampus. Our findings provide insights into the dynamic role of the
hippocampus in the maturation of memory-based problem solving and establish a
critical link between hippocampal-neocortical reorganization and children's
cognitive development.
PMID- 25129075
TI - Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1,
RHBDF2 and other loci.
AB - We used a collection of 708 prospectively collected autopsied brains to assess
the methylation state of the brain's DNA in relation to Alzheimer's disease (AD).
We found that the level of methylation at 71 of the 415,848 interrogated CpGs was
significantly associated with the burden of AD pathology, including CpGs in the
ABCA7 and BIN1 regions, which harbor known AD susceptibility variants. We
validated 11 of the differentially methylated regions in an independent set of
117 subjects. Furthermore, we functionally validated these CpG associations and
identified the nearby genes whose RNA expression was altered in AD: ANK1, CDH23,
DIP2A, RHBDF2, RPL13, SERPINF1 and SERPINF2. Our analyses suggest that these DNA
methylation changes may have a role in the onset of AD given that we observed
them in presymptomatic subjects and that six of the validated genes connect to a
known AD susceptibility gene network.
PMID- 25129079
TI - [NCCN Asian consensus statement - can Asian patients with cancer accept treatment
modalities from NCCN guidelines ?].
AB - To spread the National Comprehensive Cancer Network(NCCN)guidelines widely in
Asia, committee members from Asian countries have been preparing an Asia
Consensus Statement(ACS)along the NCCN guidelines. The ACS for Kidney Cancer
guidelines and Prostate Cancer guidelines were issued in 2009 and in 2011,
respectively. In addition, second versions of both these guidelines were issued
in 2011 and 2013, respectively. In this review, the process and contents of NCCN
ACS have been described.
PMID- 25129080
TI - [Overview of guidelines for proper use of the G-CSF(2013 edition)].
AB - Guidelines for proper use of the G-CSF(2001 edition)by the Japan Society of
Clinical Oncology have been revised the first time in 12 years. The differences
between the first edition and the new one are as follows: The new guidelines(2013
edition) adopted the clinical question format, and used the level of evidence and
recommendation grades, along with the Handbook of Clinical Guidelines of
Minds(2007 edition). There are relatively few evidence-based randomized
controlled trials(RCTs) that can inform G-CSF use in Japan at present. Thus, we
had to select the evidence from RCTs conducted in Europe and the USA when setting
the recommendation level. Guidelines from Europe and the USA were also referred
to; however, because the incidence of febrile neutropenia(FN)is presumed to
differ between Japan and the USA/Europe, the clinical trials conducted in Japan
were investigated as much as possible. New chapters on topics such as
biosimilars, pegfilgrastim(domestic non-release), and the dosage and method of G
CSF administration(medical insurance in Japan)were added. The chemotherapy
regimen-specific incidence of FN in Japan for primary prophylactic G-CSF
administration and G-CSF use in hematological malignancy were described in
detail. Nurses, pharmacists, and medical doctors participated in guideline
steering committee, because the new guidelines are directed at a wide range of
health care workers.
PMID- 25129078
TI - The GABAergic parafacial zone is a medullary slow wave sleep-promoting center.
AB - Work in animals and humans has suggested the existence of a slow wave sleep (SWS)
promoting/electroencephalogram (EEG)-synchronizing center in the mammalian lower
brainstem. Although sleep-active GABAergic neurons in the medullary parafacial
zone (PZ) are needed for normal SWS, it remains unclear whether these neurons can
initiate and maintain SWS or EEG slow-wave activity (SWA) in behaving mice. We
used genetically targeted activation and optogenetically based mapping to examine
the downstream circuitry engaged by SWS-promoting PZ neurons, and we found that
this circuit uniquely and potently initiated SWS and EEG SWA, regardless of the
time of day. PZ neurons monosynaptically innervated and released synaptic GABA
onto parabrachial neurons, which in turn projected to and released synaptic
glutamate onto cortically projecting neurons of the magnocellular basal
forebrain; thus, there is a circuit substrate through which GABAergic PZ neurons
can potently trigger SWS and modulate the cortical EEG.
PMID- 25129081
TI - [Primary and secondary prophylactic administration of granulocyte-colony
stimulating factor(G-CSF)for febrile neutropenia].
AB - The Japanese guidelines for the proper use of granulocyte-colony stimulating
factor(G-CSF)have been revised on the basis of the current international
guidelines and latest evidence. The guidelines for primary and secondary
prophylactic administration of G-CSF are clearly defined in the revised version.
Primary prophylactic administration is recommended as per the incidence of
febrile neutropenia(FN): it is highly recommended for patients with an FN
rate>20%, but selectively recommended for patients with an FN rate<20%. Secondary
prophylactic administration is recommended only for patients who should be
maintained on a constant dose of G-CSF for curative purposes. The revised version
aims to improve, not limit, the clinical use of G-CSF based on both patient- and
evidence-oriented decisions in clinical practice.
PMID- 25129082
TI - [Appropriate use of granulocyte colony-stimulating factor in the management of
hematologic malignancies].
AB - There are two main types of therapy for hematologic malignancies: intensive
cytotoxic chemotherapy and hematopoietic stem cell transplantation(HSCT). The
roles of granulocyte colony-stimulating factor(G-CSF)in patients receiving HSCT
are the mobilization of hematopoietic stem cells/progenitor cells into peripheral
blood and the enhancement of neutrophil recovery as therapy or prophylaxis for
fatal complications following HSCT. In the treatment of acute leukemias, G-CSF is
used as therapy or prophylaxis for febrile complications during remission
induction and post-remission therapies. In the treatment of lymphomas, primary
prophylactic G-CSF is recommended during all cycles of chemotherapy when the
expected incidence of neutropenic fever is more than 20% or when the patient is
treated with potentially curative regimens. G-CSF is used as secondary
prophylaxis to maintain dose intensity in patients with lymphomas treated in
settings where reductions in chemotherapy dose intensity or dose density are
associated with poorer prognosis. In the treatment of multiple myelomas,
prophylactic G-CSF can be used when there is a high estimated risk of neutropenic
fever(e. g., in patients receiving high-dose chemotherapy). For all cases, the
appropriate use of G-CSF is recommended in accordance with the guidelines of the
American Society of Clinical Oncology(ASCO), European Organisation for Research
and Treatment of Cancer(EORTC), Infectious Diseases Society of America(IDSA),
National Comprehensive Cancer Network(NCCN), and our JSCO-2013.
PMID- 25129083
TI - [Use of granulocyte-colony stimulating factor(G-CSF)in patients with cancer at
high risk of febrile neutropenia on the basis of high age and complications,
recommendations for patients receiving radiotherapy, and adverse events because
of G-CSF].
AB - Neutropenic complications are the primary dose-limiting toxic effects observed in
patients treated with systemic cancer chemotherapy. Broad-spectrum antibiotic
therapy should be promptly administered to patients with febrile neutropenia(FN).
The risk assessment of FN includes the disease characteristics, chemotherapy
regimen, individual patient risk factors, and treatment intent. After considering
such risk factors of FN, clinicians should appropriately consider the use of
granulocytecolony stimulating factor(G-CSF)as a prophylactic or therapeutic
measure. Some types of lymphoma can be cured with chemotherapy. The incidence of
FN in patients receiving the standard rituximab, cyclophosphamide, doxorubicin,
vincristine, and prednisone(R-CHOP)regimen is approximately 20%. Primary
prophylactic use of G-CSF is recommended for patients agedB 65 years having
diffuse aggressive lymphoma and treated with curative chemotherapy in an effort
to improve their quality of life(QOL). Primary prophylaxis is recommended for the
prevention of FN in patients at high risk, on the basis of factors other than
age. G-CSF should be avoided in patients receiving concomitant chemotherapy and
radiation therapy, particularly in those with cancer involving the mediastinum.
The adverse events of G-CSF are generally graded mild to moderate; however, rare
life-threatening adverse effects have been published in the literature. A
clinical practice guideline for the use of G-CSF was published by the Japan
Society of Clinical Oncology in 2013. On the basis of this guideline, the above
issues have been discussed in this paper.
PMID- 25129077
TI - Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's
disease.
AB - Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is
characterized by progressive neuropathology and cognitive decline. We performed a
cross-tissue analysis of methylomic variation in AD using samples from four
independent human post-mortem brain cohorts. We identified a differentially
methylated region in the ankyrin 1 (ANK1) gene that was associated with
neuropathology in the entorhinal cortex, a primary site of AD manifestation. This
region was confirmed as being substantially hypermethylated in two other cortical
regions (superior temporal gyrus and prefrontal cortex), but not in the
cerebellum, a region largely protected from neurodegeneration in AD, or whole
blood obtained pre-mortem from the same individuals. Neuropathology-associated
ANK1 hypermethylation was subsequently confirmed in cortical samples from three
independent brain cohorts. This study represents, to the best of our knowledge,
the first epigenome-wide association study of AD employing a sequential
replication design across multiple tissues and highlights the power of this
approach for identifying methylomic variation associated with complex disease.
PMID- 25129084
TI - [Efficacy and safety of panitumumab for K-ras wild-type unresectable or recurrent
colorectal cancer - a study focusing on first-line treatment].
AB - Panitumumab was approved in June 2010 for use in the treatment of unresectable
advanced/recurrent colorectal cancer. Here, we report outcomes and adverse events
of panitumumab combination therapy or single-agent chemotherapy for K-ras wild
type unresectable or recurrent colorectal cancers. Our study focused on first
line treatments. The study involved 18 patients who started receiving panitumumab
in October 2010. Nine patients received panitumumab as a first-line treatment; 4,
as a second-line treatment; and 5, as a third-line or subsequent treatment. The
overall response rate was 27.8%. Among the patients who received panitumumab as a
first-line treatment, the response rate was 55.6%. Grade 1 and 2 skin disorders
were common adverse events. Grade 2 interstitial pneumonia was observed in 1
patient(5.6%). Grade 3 or higher events comprised peripheral neuropathy in 1
patient(5.6%)and neutropenia in another patient(5.6%). The treatment was
beneficial, and metastatic foci were resected in 3 patients. In this study, the
only adverse events of Grade 3 or higher were 1 case each of peripheral
neuropathy and neutropenia. Accordingly, adequate control seemed possible. The
specific line of treatment that panitumumab should belong to remains
controversial. However, active initiation as first-line treatment should be
considered for cases in which resection of metastatic foci can be expected from
tumor reductions due to panitumumab.
PMID- 25129085
TI - [Retrospective analysis of the bevacizumab and CapeOX combination in untreated
metastatic/recurrent colorectal cancer].
AB - In recent years, there has been significant progress in systemic chemotherapy for
metastatic or recurrent colorectal cancer. We investigated the clinical efficacy
and feasibility of the bevacizumab and capecitabine
/oxaliplatin(CapeOX)combination for untreated colorectal cancer. From October
2009 to June 2012, 38 patients were included, 18 receiving CapeOX alone and 20
receiving CapeOX plus bevacizumab. The response rate and disease-control rate
were 16% and 5 0%, respectively, in the CapeOX arm, and 5 5% and 8 5%,
respectively, in the CapeOX plus bevacizumab arm. Median progression-free
survival was 8.0 months in the CapeOX arm and 1 2.8 months in CapeOX plus
bevacizumab arm. The median overall survival was 21.6 months in the CapeOX arm
and 3 4.0 months in CapeOX plus bevacizumab arm. Our results suggest that CapeOX
treatment can be useful in the outpatient setting and more effective when
combined with bevacizumab. Except in cases of bevacizumab intolerance, addition
of bevacizumab to CapeOX treatment is considered useful as first-line therapy for
metastatic or recur- rent colorectal cancer.
PMID- 25129086
TI - [Tolerability of XELOX in postoperative adjuvant chemotherapy for colorectal
cancer].
AB - A regimen of capecitabine plus oxaliplatin(XELOX)has become one of the standard
postoperative adjuvant chemotherapies for colon cancer. However, few tolerability
studies have been conducted in Japan. In this study, we retrospectively examined
treatment continuation and the adverse events that occurred during 8 courses of
postoperative adjuvant chemotherapy with XELOX in 21 patients with colorectal
cancer who had undergone curative resection. The completion rate for 8 courses of
treatment with XELOX was 71.4%, while the median relative dose intensities of
capecitabine and oxaliplatin were 85.0% and 75.0%, respectively. Although the
incidence of subsequent Grade 3 or higher hand-foot syndrome was 14.3%, the rate
of peripheral neuropathy was 0%. Our hospital had a high rate of XELOX treatment
continuation, suggesting that XELOX adjuvant chemotherapy would be well tolerated
in clinical practice as well.
PMID- 25129087
TI - [Evaluation of breath alcohol concentration after the administration of alcohol
based docetaxel].
AB - In the present study, we measured breath alcohol concentration(BAC)after the
administration of alcohol-containing docetaxel(OTX)in breast cancer patients, and
examined the safety of OTX outpatient administration. Twenty breast cancer
patients who received OTX chemotherapy at our outpatient facility were included.
The administered doses were 100mg/m2 in 5 cases, 75mg/m / 2 in 13 cases, and 60
mg/m2 in 2 cases. BAC was measured 3 times: immediately after infusion, 30
minutes after infusion, and 60 minutes after infusion. No symptoms of hot flash
or drunkenness due to alcohol were observed. BAC was detected in 10
cases(50%)immediately after infusion, in 7 cases(35%)at 30 minutes after
infusion, and in 1 case(5%) at 60 minutes after infusion. BAC was more than
0.15mg/L in only 1 case(5%)and reduced to less than 0.15mg/L in all cases after
30 minutes. Our results suggest that the effects of alcohol are alleviated 60
minutes after infusion and that patients receiving OTX could return home safely.
PMID- 25129088
TI - Seasonal variations in breast cancer diagnosis in Osaka, Japan.
AB - To date, seasonal variations in breast cancer diagnosis have been reported in
Western countries. In the present study, we calculated the number of breast
cancer diagnoses according to season between 1976 and 2005, using data from the
Osaka Cancer Registry. In all time periods and all age groups, breast cancer
diagnosis showed peaks in early summer and troughs in winter. The number of
breast cancer diagnoses in the spring, summer, autumn, and winter were
2,595(26%), 2,739(27%), 2,585(26%), and 2,120(21%)in 1976-1985; 4,219(26%),
4,581(28%), 4,2 62(26%), and 3,466(21%)in 1986-1995; and 6,299(25%), 6,852(28%),
6,368(26%), and 5,335(22%)in 1996-2005, respectively. Most cases were diagnosed
because of an awareness of a breast mass. The trend in screening-detected cases
differed from the overall trend. As screening becomes more widely adopted, these
seasonal variations might change. Careful monitoring is needed to confirm these
findings.
PMID- 25129089
TI - [A case of recurrent lung cancer with bone metastases treated with tegafur-uracil
and zoledronic acid for long-term survival].
AB - We present the case of an 84-year-old man with lumbago due to bone metastases
from lung cancer that recurred three years after surgery. The patient received
carboplatin-paclitaxel combination as first-line chemotherapy for the treatment
of lung cancer, and palliative radiotherapy for the treatment of bone metastases.
Gemcitabine was administered as second-line chemotherapy. However, disease
progression was observed after three years, and he developed pulmonary
metastases. The general condition of the patient worsened, and tegafur-uracil
chemotherapy was initiated. Zoledronic acid was also administered. The tegafur
uracil treatment resulted in the disappearance of pulmonary metastases, and a
stabilization of the bone metastases. Disease progression was observed after 6
years with a recurrence of pulmonary metastases; however, this did not have a
negative impact on the patient's quality of life. Although slow progression may
be inherent to lung cancers, it is also possible that the tegafur-uracil and
zoledronic acid combination might have contributed to the patient's improved
performance.
PMID- 25129090
TI - [Analysis of factors associated with the quality of life in patients with non
small cell lung cancer who received outpatient pemetrexed maintenance therapy].
AB - Increasing number of patients with advanced non-small cell lung cancer are
receiving outpatient maintenance chemotherapy. It is very important to maintain
these patients' quality of life(QOL). Pemetrexed has been reported to be an
effective maintenance chemotherapy. However, its effects on the QOL of patients
with non-small cell lung cancer who are undergoing outpatient maintenance
chemotherapy are unknown; therefore, we conducted this study. To investigate
factors that influence the QOL of these patients, we provided a QOL
questionnaire,"The QOL Questionnaire for Cancer Patients Treated with Anticancer
Drugs(QOL-ACD)"to 7 patients with non-small cell lung cancer. The medical factors
related to the overall QOL scores, as well as other categories
indicating"activity","physical condition","psychological condition","social
relationship", and"face scale", were analyzed. No significant reductions in any
of the factors were observed in this study.
PMID- 25129091
TI - [Neuroendocrine gallbladder cancer treated with cisplatin plus irinotecan - a
case report].
AB - A 52-year-old woman was referred to our hospital because of upper abdominal pain.
A computed tomography(CT)scan revealed bulky gallbladder and liver tumors. We
reached a tentative diagnosis of invasive adenocarcinoma of the gallbladder and
performed needle biopsy of the tumor. Biopsied specimens showed the proliferation
of small round to oval cells with scanty cytoplasm and high rates of mitosis.
Immunohistochemical examination showed that many tumor cells were positive for
chromogranin A, synaptophysin, and CD56. Our final diagnosis was neuroendocrine
carcinoma of the gallbladder with multiple liver metastases. The patient received
cisplatin plus irinotecan chemotherapy. Remarkable shrinkage was observed after 3
cycles of chemotherapy, and a good response continued for more than 6 months.
Gallbladder cancer patients generally have a poor response to chemotherapy, so we
should be aware of the histopathological diagnosis of the cancer before starting
treatment.
PMID- 25129092
TI - [A patient with advanced breast cancer who developed bacterial meningitis after
chemotherapy].
AB - A 76-year-old woman was admitted to our hospital because of a right breast tumor
and a skin ulcer. The patient was diagnosed as having advanced breast cancer
T4bN2M1(lung), Stage IV. A regimen of 5-fluorouracil(500mg/m2)with
epirubicin(100mg/m / 2)and cyclophosphamide(500mg/m2)(FEC100)was administered.
However, the patient was hospitalized 12 days later because of febrile
neutropenia. The patient experienced a stiff neck the next day, and bacterial
meningitis was diagnosed on the basis of cerebrospinal fluid examination.
Antibacterial agents were administered according to the clinical practice
guidelines of bacterial meningitis. The patient recovered and was discharged from
our hospital 24 days after admission. Bacterial meningitis after chemotherapy is
rare, but this could be progress to a serious condition. Early diagnosis and
treatment are paramount in such cases.
PMID- 25129093
TI - [A case of a patient with gastric cancer and peritoneal dissemination who
survived for more than 10 years after successful treatment with S-1].
AB - A 50-year-old female patient underwent distal gastrectomy and intraperitoneal
CDDP administration for advanced gastric cancer accompanied by severe peritoneal
dissemination. She valued her quality of life and chose an oral anticancer drug,
S-1, as a postoperative chemotherapy agent. S-1 was administered at a dose of
100mg/body/day for 4 weeks, followed by a 2- week rest. There were no adverse
events due to S-1 and no exacerbation of peritoneal dissemination in the 5 years
following surgery. The S-1 administration schedule was then changed to alternate
day administration. Eight years after the surgery, the patient discontinued S-1
treatment and has since survived for 11 years with no obvious cancer recurrence.
PMID- 25129094
TI - [A case of pathologically complete response in a patient with locally advanced
sigmoid colon cancer after chemotherapy including bevacizumab/FOLFOX4].
AB - A 65-year-old man complaining of abdominal pain was admitted to our hospital. A
diagnosis of colon ileus due to sigmoidal colon cancer was made. A stoma was
created at the transverse colon, and elective surgery was scheduled. During the
operation, the tumor was found to have invaded the bladder and the pelvic wall,
making curative resection impossible. Chemotherapy consisting of
bevacizumab/oxaliplatin, Leucovorin, and 5-fluorouracil(FOLFOX4, intravenous drip
infusion every 2 weeks)was started. After 12 courses of treatment, remarkable
shrinkage of the tumor was noted, which led us to perform a sigmoidectomy and
partial resection of the bladder wall. A histopathological study of the
surgically resected specimen showed no cancer cells. Recovery was uneventful and
the patient was discharged on the 17th postoperative day. In cases of advanced
colon cancer, complete response of the primary tumor with preoperative
chemotherapy is very unusual. We conclude that chemotherapy with
bevacizumab/FOLFOX4 plays a role in the management of advanced/unresectable colon
cancer.
PMID- 25129095
TI - [Effectiveness of azacitidine in chronic myelomonocytic leukemia harboring
del(20q) - a case report].
AB - A 7 1-year-old man was admitted to our hospital with leukocytosis and anemia.
Chronic myelomonocytic leukemia (CMML)harboring del(20q)was diagnosed by
peripheral blood examination and bone marrow aspiration. The patient was
subsequently treated with azacitidine, which resulted in rapid disappearance of
monocytosis and resolved his dependency on red cell transfusion. With regard to
the chromosomal abnormality, although del(20q)is estimated to be encountered in
approximately 0.7-1.0% of all CMML cases, its significance in prognosis has not
been fully analyzed. Hence, more such cases need to be evaluated to elucidate the
therapeutic outcome of CMML involving del(20q). In addition, the Wilms tumor-1(WT
1)level in the patient gradually decreased after the initiation of azacitidine
therapy. This phenomenon of WT1 decrease synchronizing with the patient's
clinical improvement might reflect therapeutic efficacy with regard to the
clinical course, as had been observed in acute myeloid leukemia and
myelodysplastic syndrome.
PMID- 25129096
TI - [A case of small intestinal cancer in the upper intestine after pylorus
preserving pancreaticoduodenectomy].
AB - We report a case of small intestinal cancer that arose in the upper intestine 16
years after pylorus-preserving pancreaticoduodenectomy( PPPD). An 84-year-old
man, who had undergone PPPD for benign biliary tract disease 16 years previously,
was found to have a primary small intestinal tumor in the upper intestine by
upper gastrointestinal endoscopy, and primary intestinal cancer in the upper
intestine was finally diagnosed. We performed partial resection of the upper
small intestine and stomach and partial colectomy of the transverse colon to
account for direct invasion. Histopathologically, the primary lesion was
diagnosed as a moderately to poorly differentiated adenocarcinoma. Small
intestinal cancer in the upper intestine after PPPD is extremely rare.
PMID- 25129097
TI - [A case report of primary adenocarcinoma of the small intestine with peritoneal
dissemination treated with multidisciplinary therapy].
AB - A 55-year-old woman consulted our hospital complaining of abdominal distention
and vomiting. She was diagnosed with a malignant tumor in the small intestine and
an ovarian tumor with an upper gastro-intestinal series based on a computerized
tomography(CT)examination. Intra-operative findings showed that the primary tumor
was located in the proximal jejunum, 10 cm on the anal side from Treitz's
ligament. There were no liver metastases, but the tumor had spread into the
peritoneal cavity(light ovary). The jejunum and light ovary were therefore
resected. Pathological diagnosis of the resected specimen revealed adenocarcinoma
with lymph node metastases(T4N1M1, UICC StageIV). The patient received systemic
chemotherapy with oral S-1. A recurrent lesion on the right ovary was detected 6
months after surgery. The patient subsequently underwent resection of the right
ovary. For lung metastases and recurrent peritoneal dissemination, combination
chemotherapy with XELOX or FOLFIRI, along with capecitabine plus bevacizumab, and
cetuximab, was administered. The patient died 33 months after the first surgery.
Primary small intestinal adenocarcinoma is a rare disease, and it is often
diagnosed at an advanced stage because there are very few characteristic
symptoms. This case may be an important case for the development of a standard
chemotherapy regimen for advanced and recurrent adenocarcinoma of the small
intestine.
PMID- 25129098
TI - Neurolysis for secondary sciatic nerve entrapment: evaluation of surgical
feasibility and functional outcome.
AB - BACKGROUND: The study included 11 patients; seven males and four females with
mean age of 68.3 +/-11 years. All patients had sciatic nerve entrapment: three
had a penetrating injury, three suffered postoperative trauma, two had a crush
injury, two had inadvertent injections and one was trapped in a machine belt.
Clinical examination included: an evaluation of the extent of motor and sensory
impacts according to the British Medical Research Council (BMRC) scale and the
Semmes-Weinstein monofilament test; assessment of pain sensation using the visual
analogue scale (VAS); electromyography; and nerve conduction velocitiey
determination. The applied operative procedure for sciatic neurolysis was
modulated according to the suspected site of sciatic nerve entrapment. At 6 and
12 months after surgery all patients were evaluated for recovery of motor and
sensory function. RESULTS: All patients passed the smooth intraoperative course
within a mean operative time of 77.7 +/-21 min. The mean duration of wound
drainage and postoperative hospital stay was 2.6 +/-0.7 and 4.8 +/-0.8 days,
respectively. Pain sensation showed progressive significant improvement in nine
patients but decreased at time of discharge and remained stationary till 12-m
post-operative (PO). Recovery of motor function showed progressive significant
improvement at 6 and 12 months after sciatic nerve neurolysis. The frequency of
patients having muscle power recovery and regained sensation was significantly
higher at 6-m and 12-m PO as compared to preoperative grading with a
significantly higher frequency at the 6-m grading compared to preoperative
grading. Two patients showed no change of their muscle strength grade, while nine
patients showed improvement for a total success rate of motor strength recovery
of 81.8%. At 6- m PO five patients showed no change of their sensory group, while
six patients showed improvement for a total success rate of sensation recovery of
54.5%. At 12-m PO ten patients had fullly recovered protective sensation for a
success rate of 90.9%. CONCLUSION: Surgical exploration and neurolysis of cases
with sciatic nerve entrapment is a safe and effective therapeutic modality with
significant improvement of both motor and sensory functions without risk of
additional deficit secondary to neurolysis.
PMID- 25129099
TI - Quercetin glycosides induced neuroprotection by changes in the gene expression in
a cellular model of Parkinson's disease.
AB - Quercetin glycosides, rutin and isoquercitrin, are potent antioxidants that have
been found to possess neuroprotective effect in diseases like Parkinson's and
Alzheimer's disease. In the present study, we have examined the gene expression
changes with rutin and isoquercitrin pretreatment on 6-hydroxydopamine (6-OHDA)
treated toxicity in rat pheochromocytoma (PC12) cells. PC12 cells were pretreated
with rutin or isoquercitrin and subsequently exposed to 6-OHDA. Rutin-pretreated
PC12 attenuated the Park2, Park5, Park7, Casp3, and Casp7 genes which were
expressed significantly in the 6-OHDA-treated PC12 cells. Rutin upregulated the
TH gene which is important in dopamine biosynthesis, but isoquercitrin
pretreatment did not affect the expression of this gene. Both rutin and
isoquercitrin pretreatments upregulated the ion transport and antiapoptotic genes
(NSF and Opa1). The qPCR array data were further validated by qRT-PCR using four
primers, Park5, Park7, Casp3, and TH. This finding suggests that changes in the
expression levels of transcripts encoded by genes that participate in ubiquitin
pathway and dopamine biosynthesis may be involved in Parkinson's disease.
PMID- 25129100
TI - Microvascular lesions by estrogen-induced ID3: its implications in cerebral and
cardiorenal vascular disease.
AB - Severe symptoms of cerebral and cardiorenal vascular diseases can be triggered
when cerebral, coronary, or glomerular arterioles grow inappropriately as a
result of abnormal cell proliferation. The risk factor(s) and molecular
mechanisms responsible for microvascular lesion formation are largely unknown.
Although controversial, both animal and epidemiological studies have shown that
estrogen increases the risk of stroke which may be due to microvascular lesions.
Since microvascular diseases are characterized by excessive vessel growth, it is
plausible that estrogen-induced neovascularization contributes to the growth of
microvascular lesions. We present evidence for how ID3 overexpression in
endothelial cells contributes to the development of an estrogen-induced
neovascular phenotype with an additional focus on Pyk2 kinase. Our data showed
that ID3 overexpression increased neovascularization, cell migration, and
spheroid growth of human cerebral microvascular endothelial cells, hCMEC/D3. ID3
overexpressing cells showed significant estrogen-induced G2/M phase transition.
Estrogen treatment increased both ID3 phosphorylation; total protein that was
inhibited by tamoxifen, and Pyk2-mediated estrogen-induced ID3 mRNA expression.
These findings suggest that Pyk2 signals ID3 expression and ID3 is necessary for
estrogen-induced neovascularization in hCMEC/D3 cells. A better understanding of
how microvascular lesions depend on ID3 may open new avenues for prevention and
treatment of neurological diseases.
PMID- 25129101
TI - Qualitative and Quantitative Assessment of Hepatitis A Virus in Wastewaters in
Tunisia.
AB - Hepatitis A causes substantial morbidity in both industrialized and non
industrialized countries and represents an important health problem in several
southern Mediterranean countries. The objectives of the study were as follows:
(a) to assess the occurrence of hepatitis A virus (HAV) in Tunisia through the
monitoring of urban wastewaters collected at wastewater treatment plants (WTPs);
(b) to characterize environmental strains; and (c) to estimate the viral load in
raw and treated sewages, in order to evaluate the potential impact on superficial
waters receiving discharges. A total of 150 raw and treated wastewaters were
collected from three WTPs and analyzed by both qualitative (RT-PCR/nested) and
quantitative (qRT-PCR) methods. Of these, 100 (66%) were found to be positive for
HAV by the qualitative assay: 68.3% in influents and 64.7% in effluents. The vast
majority of HAV sequences belonged to sub-genotype IA, with 11 different strains
detected found to be identical to clinical strains isolated from Tunisian
patients with acute hepatitis. Five unique variants were also detected, not
previously reported in clinical cases. Only two IB strains were found, confirming
the rarity of this sub-genotype in this country. The results of the present study
indicate a wide circulation of the pathogen in the population, most probably in
the form of asymptomatic infections, a finding consistent with the classification
of the country as having intermediate/high endemicity. Quantitative data showed
high viral loads in influents (3.5E+05 genome copies/liter, mean value) as well
as effluents (2.5E+05 genome copies/liter, mean value), suggesting that
contaminated water could be a critical element in transmission.
PMID- 25129102
TI - Antiviral Effects of Lactococcus lactis on Feline Calicivirus, A Human Norovirus
Surrogate.
AB - Foodborne viruses, particularly human norovirus (NV) and hepatitis virus type A,
are a cause of concern for public health making it necessary to explore novel and
effective techniques for prevention of foodborne viral contamination, especially
in minimally processed and ready-to-eat foods. This study aimed to determine the
antiviral activity of a probiotic lactic acid bacterium (LAB) against feline
calicivirus (FCV), a surrogate of human NV. Bacterial growth medium filtrate
(BGMF) of Lactococcus lactis subsp. lactis LM0230 and its bacterial cell
suspension (BCS) were evaluated separately for their antiviral activity against
FCV grown in Crandell-Reese feline kidney (CRFK) cells. No significant antiviral
effect was seen when CRFK cells were pre-treated with either BGMF (raw or pH 7
adjusted BGMF) or BCS. However, pre-treatment of FCV with BGMF and BCS resulted
in a reduction in virus titers of 1.3 log10 tissue culture infectious dose
(TCID)50 and 1.8 log10 TCID50, respectively. The highest reductions in FCV
infectivity were obtained when CRFK cells were co-treated with FCV and pH 7
adjusted BGMF or with FCV and BCS (7.5 log10 TCID50 and 6.0 log10 TCID50,
respectively). These preliminary results are encouraging and indicate the need
for continued studies on the role of probiotics and LAB on inactivation of
viruses in various types of foods.
PMID- 25129103
TI - Tachykinin Peptide, substance p, and its receptor have a significant role in
tissue reactions induced by cytotoxic therapy.
PMID- 25129105
TI - Does endoscopic assessment of mucosal healing affect IBD management?
PMID- 25129104
TI - The transcription factor FOXA2 suppresses gastric tumorigenesis in vitro and in
vivo.
AB - BACKGROUND AND AIMS: The transcription factor forkhead box A2 (FOXA2) plays a
central role in the development of endoderm-derived organs. It has been reported
that FOXA2 acts as a suppressor in many kinds of tumor. However, little is known
about the role of FOXA2 in gastric cancer. METHODS: The expression of FOXA2 in
gastric cancer tissue samples from 89 patients was assessed by
immunohistochemistry, and the clinicopathological characteristics of the samples
were analyzed. The human gastric cancer cell line, BGC-823, was used to
investigate the effects of FOXA2 in gastric cancer in vitro and in vivo and the
potential mechanism involved was explored. RESULTS: FOXA2 expression in human
gastric cancer cell lines and human gastric cancer tissues was lower compared
with the normal gastric epithelium cell line GES1 and normal adult gastric
tissues, respectively. Patients with high FOXA2 expression level had longer 5
year overall survival than those with low FOXA2 expression level. FOXA2 markedly
inhibited growth of BGC-823 cells accompanied with the cell cycle arrest and
apoptosis. Infection of BGC-823 cells by FOXA2 lentivirus resulted in reduced
cell tumorigenesis in vitro and in vivo. Moreover, expression of Mucin 5AC was up
regulated along with increased expression of exogenous FOXA2 in BGC-823 cells; in
contrast, dedifferentiation markers, BMI, CD54 and CD24, were down-regulated.
CONCLUSIONS: These results suggest that FOXA2 induces the differentiation of
gastric cancer and highlight FOXA2 as a novel therapeutic target and prognostic
marker for human gastric cancer.
PMID- 25129106
TI - Proton receptor GPR68 expression in dendritic-cell-like S100beta-positive cells
of rat anterior pituitary gland: GPR68 induces interleukin-6 gene expression in
extracellular acidification.
AB - S100beta-positive cells, which do not express the classical pituitary hormones,
appear to possess multifunctional properties and are assumed to be heterogeneous
in the anterior pituitary gland. The presence of several protein markers has
shown that S100beta-positive cells are composed of populations such as
stem/progenitor cells, epithelial cells, astrocytes and dendritic cells.
Recently, we succeeded in separating S100beta-positive cells into round-cell
(dendritic-cell-like) and process-cell types. We also found the characteristic
expression of anti-inflammatory factors (interleukin-6, Il-6) and membrane
receptors (integrin beta-6) in the round type. Here, we further investigate the
function of the subpopulation of S100beta-positive cells. Since IL-6 is also a
paracrine factor that regulates hormone producing-cells, we examine whether a
correlation exists among extracellular acid stress, IL-6 and hormone production
by using primary cultures of anterior pituitary cells. Dendritic-cell-like
S100beta-positive cells notably expressed Gpr68 (proton receptor) and Il-6.
Furthermore, the expression of Il-6 and proopiomelanocortin (Pomc) was up
regulated by extracellular acidification. The functional role of IL-6 and GPR68
in the gene expression of Pomc during extracellular acidification was also
examined. Small interfering RNA for Il-6 up-regulated Pomc expression and that
for Gpr68 reversed the down-regulation of Il-6 and up-regulated Pomc expression
by extracellular acidification. Thus, S100beta-positive dendritic-like cells can
sense an increase in extracellular protons via GPR68 and respond by the
production of IL-6 in order to suppress the up-regulation of Pomc expression.
PMID- 25129107
TI - Involvement of RhoA/ROCK in insulin secretion of pancreatic beta-cells in 3D
culture.
AB - Cell-cell contacts and interactions between pancreatic beta-cells and/or other
cell populations within islets are essential for cell survival, insulin
secretion, and functional synchronization. Three-dimensional (3D) culture systems
supply the ideal microenvironment for islet-like cluster formation and functional
maintenance. However, the underlying mechanisms remain unclear. In this study,
mouse insulinoma 6 (MIN6) cells were cultured in a rotating 3D culture system to
form islet-like aggregates. Glucose-stimulated insulin secretion (GSIS) and the
RhoA/ROCK pathway were investigated. In the 3D-cultured MIN6 cells, more
endocrine-specific genes were up-regulated, and GSIS was increased to a greater
extent than in cells grown in monolayers. RhoA/ROCK inactivation led to F-actin
remodeling in the MIN6 cell aggregates and greater insulin exocytosis. The gap
junction protein, connexin 36 (Cx36), was up-regulated in MIN6 cell aggregates
and RhoA/ROCK-inactivated monolayer cells. GSIS dramatically decreased when Cx36
was knocked down by short interfering RNA and could not be reversed by RhoA/ROCK
inactivation. Thus, the RhoA/ROCK signaling pathway is involved in insulin
release through the up-regulation of Cx36 expression in 3D-cultured MIN6 cells.
PMID- 25129108
TI - A new role of Klumpfuss in establishing cell fate during the GMC asymmetric cell
division.
AB - Studies in the Drosophila embryonic NB4-2 lineage have suggested that the
transcription factor Klumpfuss (Klu) functions within embryonic neuroblast
lineages to differentiate between the identities of two adjacent ganglion mother
cells (GMCs). However, because of the limited lineage markers available, these
observations have been made only for the NB4-2 lineage. Recent findings have
placed this transcription factor in the vanguard of Drosophila neural stem cell
biology by demonstrating that Klu is necessary for larval neuroblast growth and
self-renewal. Here, we have studied the role of klu in an incipient model in
order to address basic mechanisms of neural specification: the Va system. None of
the previously reported roles of Klu satisfactorily explain our observations.
Unexpectedly, in this lineage, klu is necessary for differentiating between the
fates of the two neurons born from a unique GMC; klu mutants produce two B-type
cells, rather than one B-type (Notch-OFF) and one A-type (Notch-ON) cell.
Additionally, our results demonstrate that Klu operates in the GMC and/or in the
newly born neuron, but not in the neuroblast. Unlike in larval neuroblasts in
which Klu is an executor of Notch signaling, we have found that Klu does not lie
downstream of the Notch pathway in this cell division context.
PMID- 25129109
TI - Xenogeneic transplantation of articular chondrocytes into full-thickness
articular cartilage defects in minipigs: fate of cells and the role of
macrophages.
AB - Xenogeneic or allogeneic chondrocytes hold great potential to build up new
cartilage in vivo. However, immune rejection is a major concern for the utility
of universal donor-derived cells. In order to verify the reported immune
privilege of chondrocytes in vivo, the aim of this study was to assess
engraftment of human articular chondrocytes (HAC) in minipig knee cartilage
defects and their contribution to cartilage regeneration. HAC were transplanted
matrix-assisted within two hydrogels into full-thickness cartilage defects of
minipigs or implanted ectopically into immune deficient mice to assess
redifferentiation capacity. At 2 and 4 weeks after surgery, cell-persistence and
host cell invasion were monitored by species-specific in situ hybridization and
RT-PCR. Early tissue regeneration was evaluated by histomorphometry and a
modified O'Driscoll score. HAC capable of successful in vivo chondrogenic
redifferentiation persisted at ectopic sites for 4 weeks in both carrier
materials. Early defect regeneration involved extensive host cell invasion and a
decline of HAC to less than 5 % of initial cell numbers in 6/12 defects within 2
weeks. Few clusters of persisting HAC within collagen type II-rich tissue were
surrounded by porcine macrophages. Four weeks after cell transplantation, most of
the defects contained well-integrated cell-rich tissue free of human cells with
no apparent difference between hydrogel carriers. In summary, HAC failed to
engraft in porcine articular cartilage defects despite their ability for
successful in vivo redifferentiation. The co-localization of macrophages to
hydrogel-implanted HAC suggests active graft rejection without evidence for an
immune-privileged status of xenogeneic chondrocytes in a large animal joint.
PMID- 25129110
TI - Changing healthcare capital-to-labor ratios: evidence and implications for
bending the cost curve in Canada and beyond.
AB - Healthcare capital-to-labor ratios are examined for the 10 provincial single
payer health care plans across Canada. The data show an increasing trend
particularly during the period 1997-2009 during which the ratio as much as
doubled from 3 to 6 %. Multivariate analyses indicate that every percentage point
uptick in the rate of increase in this ratio is associated with an uptick in the
rate of increase of real per capita provincial government healthcare expenditures
by approximately $31 ([Formula: see text] 0.01). While the magnitude of this
relationship is not large, it is still substantial enough to warrant notice:
every percentage point decrease in the upward trend of the capital-to-labor ratio
might be associated with a one percentage point decrease in the upward trend of
per capita government healthcare expenditures. An uptick since 1997 in the rate
of increase in per capita prescription drug expenditures is also associated with
a decline in the trend of increasing per capita healthcare costs. While there has
been some recent evidence of a slowing in the rate of health care expenditure
increase, it is still unclear whether this reflects just a pause, after which the
rate of increase will return to its baseline level, or a long-term shift;
therefore, it is important to continue to explore various policy avenues to
affect the rate of change going forward.
PMID- 25129111
TI - Drug compartmentalization as strategy to improve the physico-chemical properties
of diclofenac sodium loaded niosomes for topical applications.
AB - The objective of this research was to study the effect of diclofenac sodium
compartmentalization on the physico-chemical properties (such as size, drug
entrapment efficiency and percutaneous permeation across rabbit skin) of niosomal
vesicles used as carriers. Niosomes were prepared starting from nonionic
commercial surfactants belonging to the class of Polysorbates and Pluronics:
mixtures of Span 60/F127 and Tween 60/F127 at different ratios were used to
obtain vesicles and all formulations were compared in terms of dimensions,
morphology, polydispersity index and entrapment efficiency. Moreover, the
enhancing effect of niosomes on the ex vivo percutaneous penetration of
diclofenac sodium was investigated using Franz-type diffusion chambers and
compared to that obtained by using the corresponding drug solution. Results
demonstrated that niosomes were spherical and homogeneous in shape. Their size
was found to be dependent on the hydrophile-lipophile balance of the surfactant
mixture: increasing hydrophobicity resulted in smaller vesicles. Drug
incorporation led to a significant variation in vesicle size dependently from the
compartment in which the drug was located. The permeation of diclofenac from free
solution used as control was found to be lower respect to that obtained for all
niosomal formulations, that can be considered as percutaneous permeation
enhancers. In particular, the results indicated that the highest cumulative
amounts of diclofenac permeated across rabbit skin after 24 h were obtained by
formulations in which the drug was located in the aqueous core.
PMID- 25129112
TI - A micro-drive hearing aid: a novel non-invasive hearing prosthesis actuator.
AB - The direct hearing device (DHD) is a new auditory prosthesis that combines
conventional hearing aid and middle ear implant technologies into a single
device. The DHD is located deep in the ear canal and recreates sounds with
mechanical movements of the tympanic membrane. A critical component of the DHD is
the microactuator, which must be capable of moving the tympanic membrane at
frequencies and magnitudes appropriate for normal hearing, with little
distortion. The DHD actuator reported here utilized a voice coil actuator design
and was 3.7 mm in diameter. The device has a smoothly varying frequency response
and produces a precisely controllable force. The total harmonic distortion
between 425 Hz and 10 kHz is below 0.5 % and acoustic noise generation is
minimal. The device was tested as a tympanic membrane driver on cadaveric
temporal bones where the device was coupled to the umbo of the tympanic membrane.
The DHD successfully recreated ossicular chain movements across the frequencies
of human hearing while demonstrating controllable magnitude. Moreover, the micro
actuator was validated in a short-term human clinical performance study where
sound matching and complex audio waveforms were evaluated by a healthy subject.
PMID- 25129113
TI - Shape and size of the medial patellofemoral ligament for the best surgical
reconstruction: a human cadaveric study.
AB - PURPOSE: The aim of this study was to investigate the shape and the attachments
of the medial patellofemoral ligament (MPFL) in cadaver specimens to determine an
anatomical basis for the best MPFL reconstruction. METHODS: Twenty fresh-frozen
knees were used. Dissection protocol implied performing dissections from within
the knee joint. We investigated the shape and the attachments between the MPFL
and the quadriceps tendon, the patellar and femur insertions, and all the other
relationships with the medial soft tissues of the knee. RESULTS: The distal
fibers of MPFL were interdigitated with the deep layer of the medial retinaculum.
All isolated ligament had a sail-like shape with the patellar side bigger than
the femoral side. The femoral insertion, distinct both from medial epicondyle and
adductor tubercle, was located at 9.5 mm (range 4-22) distal and anterior respect
to adductor tubercle and proximal and posterior to epicondyle. The medial third
of the thickness of patella was involved in the insertion. The proximal third of
the patella is always involved in the MPFL attachment; in 45% of the cases, it
was extended to the medial third and in one case, an extension at the distal
third was found. Additionally in 35% (7 cases), it extended to the quadriceps
tendon and it were inconstantly attached at the vastus medialis obliques (VMO)
tendon and at the vastus intermedius (VI) tendon in an aponeurotic structure.
CONCLUSIONS: The MPFL is a distinct structure that goes from patella to femur
with a sail-like shape; its patellar insertion, that mostly occur via an
aponeurosis tissue with VMO and VI, is at the proximal third of the patella but
it may extend in some cases to the medial third patella or to the quadriceps
tendon, or very rarely to the distal third of the patella. In the femoral side,
the MPFL is inserted in its own site, in most cases distinct both from epicondyle
and adductor tubercle, located on average at a 9.5 mm distance distally and
anteriorly in respect to the adductor tubercle. Its lower margin was difficult to
define. Given the importance of this structure, it must be reconstructed as
anatomically as possible in its insertion and in its shape. Many attempts have
been made to make functional reconstructions with less than excellent results.
PMID- 25129114
TI - Cutaneous manifestations of infection in returning travelers.
AB - Dermatologic problems are common in returning travelers who seek medical care.
Some common illnesses such as cellulitis or abscesses occur in travelers but are
not unique to this patient group. Additionally, dermatologic illnesses not due to
infection such as drug eruptions or phototoxicity are seen. Skin manifestations
occur in many tropical illnesses such as dengue, schistosomiasis, and
leishmaniasis. This article reviews the common causes of cutaneous illnesses
associated with travel including non-infectious causes, infections that are not
limited to travelers, and infections that are almost exclusively seen in
travelers.
PMID- 25129115
TI - Microbiology and treatment of cerebrospinal fluid shunt infections in children.
AB - Infections of cerebrospinal fluid (CSF) shunts remain a common surgical
complication causing significant morbidity in children with hydrocephalus. As
most of the literature regarding these infections includes only small cohorts
from a single institution's experience, there remain large knowledge gaps and
little support for the prevailing management strategies. Regarding the
microbiology of shunt infections, little has changed in the past 10 years, other
than the emergence of methicillin-resistant strains of coagulase-negative
staphylococcus (CoNS) and Staphylococcus aureus, which remain the two predominant
etiologic agents. Molecular diagnostics such as multiplex PCR have been used to
identify the complex microflora of shunt infections and in the future could prove
a useful adjunct for early diagnosis and targeting of antimicrobial therapy.
Antibiotic-impregnated catheters for use in external ventricular drains and CSF
shunts have been adopted into clinical practice and appear to reduce the risk of
shunt infection by susceptible organisms.
PMID- 25129116
TI - Management of Intra-abdominal Infections due to Carbapenemase-Producing
Organisms.
AB - The prevalence of bacterial resistance to carbapenem antibiotics continues to
increase because of bacteria producing metallo-beta-lactamases (MBL), called
carbapenemase-producing organisms (CPO). Enterobacteriaceae, which can be a
common cause of intra-abdominal infections (IAIs), have become carbapenem
resistant Enterobacteriaceae (CRE). Updated international guidelines for the
treatment of both IAIs and IAIs due to CRE have been published. Given the
multifaceted nature of these infections, these recommendations have been jointly
reviewed and endorsed by the Surgical Society and the Association of Medical
Microbiology and Infectious Disease. The aims of this review are to summarize the
general and new generation of multimodal procedure to manage IAIs due to CRE and
review the data available on the combination of interventions to reduce CRE.
Future research should focus on the development of novel and safe antimicrobial
therapies and the quantification of the incremental effect of infection control
programmes and new methods to rapidly detect pathogens before patients enter the
surgical setting.
PMID- 25129117
TI - Ventilator-associated conditions versus ventilator-associated pneumonia:
different by design.
AB - The Centers for Disease Control and Prevention (CDC) released a new surveillance
concept called ventilator-associated conditions (VACs) in early 2013. VAC was
created to overcome some of the limitations of traditional ventilator-associated
pneumonia (VAP) definitions, including their complexity, subjectivity, and
insensitivity to complications other than pneumonia. VAC is defined by sustained
increases in ventilator support after >=2 days of stable or decreasing settings.
The VAC definition was designed to be objective, reproducible, and amenable to
automated analysis. Moreover, VAC purposefully broadens the scope of surveillance
to include physiologically significant complications of care in addition to
pneumonia, most commonly pulmonary edema, atelectasis, and acute respiratory
distress syndrome. VAC definitions offer an opportunity for hospital quality
improvement programs to get a fuller picture of the breadth and burden of
complications in their critically ill populations and to use these data to
catalyze enhanced prevention and control programs to better prevent these
conditions.
PMID- 25129118
TI - [Pulmonary arterial hypertension associated with connective tissue diseases].
AB - Pulmonary arterial hypertension (PAH) is a classical complication of connective
tissue diseases (CTD), particularly in systemic sclerosis (SSc), systemic lupus
erythematous (SLE) or mixed connective tissue diseases (MCTD). The prevalence of
PAH in SSc, as measured by right heart catheterization (RHC), is estimated
between 7.85 to 13%. The detection of PAH in SSc is based on trans-thoracic
echocardiography. Early detection in pulmonary hypertension is the best way to
improve the survival in these diseases. In the DETECT study, 19% of high-risk PAH
patients with SSc (SSc diagnosed less than 3 years before and DLco<60% predicted)
have PAH as measured by RHC. Specific treatments for PAH are less efficient in
PAH related to SSc than in idiopathic PAH. The main characteristic of PAH related
to CTD other than SSc is a good response to immunosuppressive treatment, with an
improvement in 50% of cases in SLE or MCTD. The prognosis of PAH associated with
CTD seem to improve with the diversification of treatments available, but remains
reserved. Therapeutic combinations and new molecules should allow to improve the
prognosis.
PMID- 25129119
TI - Optic radiation damage in multiple sclerosis is associated with visual
dysfunction and retinal thinning--an ultrahigh-field MR pilot study.
AB - OBJECTIVE: To investigate posterior visual pathway damage in multiple sclerosis
using ultrahigh-field magnetic resonance imaging (MRI) at 7 Tesla (7 T), and to
determine its correlation with visual disability and retinal fibre layer (RNFL)
damage detectable by optic coherence tomography (OCT). METHODS: We studied 7 T
MRI, OCT, functional acuity contrast testing (FACT), and visually evoked
potentials (VEP, n = 16) in 30 patients (including 26 relapsing-remitting MS and
four clinically isolated syndrome patients) and 12 healthy controls to quantify
RNFL thickness, optic radiation lesion volume, and optic radiation thickness.
RESULTS: Optic radiation lesion volume was associated with thinning of the optic
radiation (p < 0.001), delayed VEP (p = 0.031), and visual disability indicated
by FACT (p = 0.020). Furthermore, we observed an inverse correlation between
optic radiation lesion volume and RNFL thickness (p < 0.001), including patients
without previous optic neuritis (p < 0.001). CONCLUSIONS: Anterior visual pathway
damage, but also (subclinical) optic radiation integrity loss detectable by 7 T
MRI are common findings in MS that are mutually affected. Given the association
between optic radiation damage, visual impairment, and increased VEP latency in
this exploratory study of a limited sample size, clinicians should be aware of
acute lesions within the optic radiation in patients with (bilateral) visual
disturbances. KEY POINTS: * Focal destruction of the optic radiation is
detectable by 7 T MRI. * Focal optic radiation damage is common in MS. * Optic
radiation damage is associated with RNFL thinning, detectable by OCT. * Optic
radiation damage is associated with delayed VEP and visual dysfunction. * RNFL
thickness in non-optic neuritis eyes correlates with optic radiation
demyelination.
PMID- 25129121
TI - Sorptive capacity of membrane lipids, storage lipids, and proteins: a preliminary
study of partitioning of organochlorines in lean fish from a PCB-contaminated
freshwater lake.
AB - Knowledge on the internal distribution of halogenated organic chemicals (HOCs)
would improve our understanding of dose-effect relationships and subsequently
improve risk assessment of contaminated sites. Herein, we determine the
concentrations of HOCs based on equilibrium partitioning in storage lipids,
membrane lipids, and proteins in field-contaminated fish using equilibrium
sampling devices. The study shows the importance of protein as a sorptive phase
in lean fish. Our results provide a basis for using species-specific equilibrium
partitioning coefficients between sorptive tissues and fish internal water as a
substitute for K(ow) in, for example, upgrading models that simulate food-chain
accumulation of the chemical.
PMID- 25129120
TI - Short- and long-term outcomes of LigaSure versus conventional surgery for
curative gastric cancer resection: a matched pair analysis.
AB - BACKGROUND: The LigaSure vessel sealing system allows dissection and hemostasis
in a safe and quick way, and it has been reported to be an effective tool to
shorten operative time and reduce intraoperative blood loss for various
surgeries. However, short- and long-term outcomes in comparison with conventional
surgery for gastric cancer resection are limited. METHODS: Between January 2005
and December 2009, 121 patients underwent curative resection for gastric cancer
with LigaSure. Perioperative and long-term results were compared with those of
242 matched patients who received curative resection for gastric cancer with the
conventional technique. Immediate operation outcomes, operation morbidity,
recurrence and survival were compared between groups. RESULTS: In the LigaSure
group compared with the conventional group, operation time was 156 versus 183 min
(P < 0.0001), intraoperative blood loss was 181 versus 236 ml (P = 0.042),
intraoperative blood transfusion was 68 versus 161 ml (P = 0.014), and hospital
stay was 11.9 versus 13.6 days (P = 0.001). There were no differences in
operation morbidity, recurrence rates, overall and disease-free survival between
the LigaSure and conventional groups. CONCLUSIONS: LigaSure is associated with
shorter operation time and hospital stay, less blood loss and transfusion, and
comparable operation morbidity and long-term outcomes in comparison with
conventional surgery for curative gastric cancer resection.
PMID- 25129122
TI - Role of thromboelastography and rapid thromboelastography to assess the
pharmacodynamic effects of vitamin K antagonists.
AB - Thromboelastography (TEG) measures the effects of antithrombotic agents by
assessing global functional clotting status by evaluating the viscoelastic
properties of in vitro clot formation. Recently, rapid TEG (r-TEG), which uses
tissue factor in addition to standard kaolin to accelerate activation of the
clotting cascade, has been proposed to obtain more immediate results. The
correlation between results of TEG or r-TEG with international normalized ratio
(INR) in patients on vitamin K antagonist (VKA) therapy has not been explored and
represents the aim of this study. Patients on chronic therapy with VKAs (n = 100)
were included in an observational prospective pharmacodynamic study. The
correlation between TEG parameters, in particular markers of thrombus generation
[Reaction time (R), maximum rate of thrombus generation (MRTG), and time to
maximum rate of thrombus generation (TMRTG)], and INR values as well as the
concordance between these parameters and therapeutic INR ranges were evaluated.
In addition, in a subgroup of subjects (n = 17), the correlation of r-TEG
parameters with TEG parameters and INR values was also assessed. No correlation
was found between INR and TEG parameters of thrombus generation, in particular
between INR and R (r = 0.189, p = 0.06), MRTG (r = -0.027, p = 0.79), and TMRTG
(r = 0.188, p = 0.06). Further, no concordance was found between these parameters
and recommended INR ranges. Significant Spearman correlations were found between
INR and activated clotting time (rS = 0.546, p < 0.001), r-R (rS = 0.572, p =
0.017), and r-TMRTG (rS = 0.510, p = 0.037), but not r-MRTG (rS = 0.131, p =
0.617). Results were obtained in 24 +/- 6 versus 12 +/- 4 min with TEG and r-TEG,
respectively (p < 0.001). In patients on chronic VKA therapy, TEG is not a useful
tool to evaluate VKA anticoagulant effect, compared with standard INR
measurements. However, r-TEG parameters of thrombus generation correlate with INR
levels, suggesting a possible role of this assay for measuring more expeditiously
anticoagulant treatment effects.
PMID- 25129123
TI - A role for membrane shape and information processing in cardiac physiology.
AB - While the heart is a dynamic organ and one of its major functions is to provide
the organism with sufficient blood supply, the regulatory feedback systems, which
allow adaptation to hemodynamic changes, remain not well understood. Our current
description of mechanosensation focuses on stretch-sensitive ion channels,
cytoskeletal components, structures such as the sarcomeric Z-disc, costameres,
caveolae, or the concept of tensegrity, but these models appear incomplete as the
remarkable plasticity of the myocardium in response to biomechanical stress and
heart rate variations remains unexplained. Signaling activity at membranes
depends on their geometric parameters such as surface area and curvature, which
links shape to information processing. In the heart, continuous cycles of
contraction and relaxation reshape membrane morphology and hence affect cardio
mechanic signaling. This article provides a brief review on current models of
mechanosensation and focuses on how signaling, cardiac myocyte dynamics, and
membrane shape interact and potentially give rise to a self-organized system that
uses shape to sense the extra- and intracellular environment. This novel concept
may help to explain how changes in frequency, and thus membrane shape, affect
cardiac plasticity. One of the conclusions is that hypertrophy and associated
fibrosis, which have been considered as necessary to cope with increased wall
stress, can also be seen as part of complex feedback systems which use local
membrane inhomogeneity in different cardiac cell types to influence whole
organphysiology and which are predicted to fine-tune and thus regulate membrane
mediated signaling.
PMID- 25129124
TI - Dipeptidyl-peptidase IV (DPP-IV) inhibitor delays tolerance to anxiolytic effect
of ethanol and withdrawal-induced anxiety in rats.
AB - Dipeptidyl-peptidase IV (DPP-IV) is an enzyme responsible for the metabolism of
endogenous gut-derived hormone, glucagon-like peptide-1 (GLP-1). DPP-IV is known
for its role in energy homeostasis and pharmacological blockade of this enzyme is
a recently approved clinical strategy for the management of type II diabetes.
Accumulating evidences suggest that enzyme DPP-IV can affect spectrum of central
nervous system (CNS) functions. However, little is known about the role of this
enzyme in ethanol-mediated neurobehavioral complications. The objective of the
present study was to examine the impact of DPP-IV inhibitor, sitagliptin on the
development of tolerance to anxiolytic effect of ethanol and anxiety associated
with ethanol withdrawal in rats. A dose-response study revealed that sitaglitpin
(20 mg/kg, p.o.) per se exhibit anxiolytic effect in the elevated plus maze (EPM)
test in rats. Tolerance to anxiolytic effect of ethanol (2 g/kg, i.p.; 8 % w/v)
was observed from 7(th) day of ethanol-diet (6 % v/v) consumption. In contrast,
tolerance to anxiolytic effect of ethanol was delayed in rats that were treated
daily with sitagliptin (20 mg/kg, p.o.) as tolerance was observed from 13(th)day
since commencement of ethanol-diet consumption. Discontinuation of rats from
ethanol-diet after 15-days of ethanol consumption resulted in withdrawal anxiety
between 8 h and 12 h post-abstinence. However, rats on 15-day ethanol-diet with
concomitant sitagliptin (20 mg/kg, p.o.) treatment exhibited delay in appearance
(24 h post-withdrawal) of withdrawal anxiety. In summary, DPP-IV inhibitors may
prove as an attractive research strategy against ethanol tolerance and
dependence.
PMID- 25129125
TI - CD44 expression in curettage and postoperative specimens of endometrial cancer.
AB - BACKGROUND: Adhesive molecules like CD44 are well defined key players in the
metastatic cascade in many cancers, including endometrial cancer. They could play
a role of markers of invasion, metastasis and prognostic factors. AIM OF THE
STUDY: The aim of the study is to assess a possible role of the CD44 as a marker
of invasion in endometrial cancer, both at the moment of preoperative workup and
final staging. MATERIALS AND METHODS: Available for analysis were archival
specimens of 51 patients who had underwent curettage and surgery between 2002 and
2007. An immunohistochemical study for CD44 expression was performed in curettage
and postoperative specimens. Normal endometrium of 20 randomly chosen patients
was used as a control group. RESULTS: In endometrial cancer the expression of
CD44 was significantly more intensive than in normal endometrium. In
postoperative specimens, the CD44 expression was weaker in serous than in
endometrioid cancer. There was no significant correlation between the adhesion
molecule expression and clinicopathological features: grade,depth of invasion,
cervical involvement, serosal and adnexal involvement, lymph-vascular space
involvement, lymph node and distant metastases nor FIGO stage. CONCLUSIONS: An
increased expression of CD44 in endometrial cancer suggests its possible role in
pathogenesis of this disease, however, it doesn't seem to be crucial. Different
expression of the CD44 in endometrioid and papillary-serous type may reflect
different pathogenesis of these types of cancer. No statistically proved relation
between the investigated molecule expression and clinicopathological parameters
suggests scepticism about its use in diagnostic process of endometrial cancer.
PMID- 25129126
TI - Regional variation in breast cancer treatment in the Netherlands and the role of
external peer review: a cohort study comprising 63,516 women.
AB - BACKGROUND: Treatment variation is an important issue in health care provision.
An external peer review programme for multidisciplinary cancer care was
introduced in 1994 in the Netherlands to improve the multidisciplinary
organisation of cancer care in hospitals.So far the clinical impact of external
quality assessment programmes such as external peer review and accreditation
remains unclear. Our objective was to examine the degree of variation in
treatment patterns and the possible effect of external peer review for
multidisciplinary cancer care for breast cancer patients. METHODS: Patients with
breast cancer were included from 23 hospitals from two 'intervention regions'
with the longest experience with the programme and 7 hospitals that never
participated (control group). Data on tumour and treatment characteristics were
retrieved from the Netherlands Cancer Registry. Treatment modalities investigated
were: the completeness of breast conserving therapy, introduction of the sentinel
node biopsy, radiotherapy after breast conserving surgery for ductal carcinoma in
situ (DCIS), adjuvant radiotherapy for locally advanced breast cancer (T3/M0 or
any T,N2-3/M0), adjuvant chemotherapy for early stage breast cancer (T1-2/N+/M0)
and neo-adjuvant chemotherapy for T4/M0 breast cancer. Hospitals from the two
intervention regions were dichotomised based on their implementation proportion
(IP) of recommendations from the final reports of each peer review (high IP vs.
low IP). This was regarded as a measure of how well a hospital participated in
the programme. RESULTS: 63,516 female breast cancer patients were included (1990
2010). Variation in treatment patterns was observed between the intervention
regions and control group. Multidisciplinary treatment patterns were not
consistently better for patients from hospitals with a high IP. CONCLUSIONS:
There is no relationship between the external peer review programme for
multidisciplinary cancer care and multidisciplinary treatment patterns for breast
cancer patients. Regional factors seem to exert a stronger effect on treatment
patterns than hospital participation in external peer review.
PMID- 25129127
TI - Utility of an initial adaptive bladder volume control with ultrasonography for
proton-beam irradiation for prostate cancer.
AB - PURPOSE: Our purpose was to evaluate the utility of time-fixed bladder volume
control and adaptive bladder volume control with ultrasonography (US). MATERIALS
AND METHODS: Seventy-five patients with prostate cancer treated with proton-beam
therapy were enrolled. Treatment plans were created using computed tomography
(CT) images obtained 60 min after urination with usual water intake. Just before
each irradiation, bladder volume was measured with US at the directed urine
collection time. Bladder volume was calculated according to orthogonal diameters.
A bladder volume of <50 ml was considered to reflect a collapsed bladder. The
percentage of collapsed bladders was examined in total and from the first to
fifth irradiations. RESULTS: In total, 1,439 US confirmations (51 %) in 2,821
fractions were obtained and analyzed. A collapsed bladder was observed 152 of
1,439 times (11 %) in total, and the percentages of collapsed bladders from the
first to fifth irradiations were 32 %, 18 %, 16 %, 12 %, and 7 %, respectively.
CONCLUSION: Time-fixed bladder control is associated with a risk of bladder
volume insufficiency. Adaptive bladder volume control with initial US feedback
could decrease the risk of bladder volume insufficiency.
PMID- 25129128
TI - High-density genetic linkage map construction and identification of fruit-related
QTLs in pear using SNP and SSR markers.
AB - Pear (Pyrus spp) is an important fruit crop, grown in all temperate regions of
the world, with global production ranked after grape and apples among deciduous
tree crops. A high-density linkage map is a valuable tool for fine mapping
quantitative trait loci (QTL) and map-based gene cloning. In this study, we
firstly constructed a high-density linkage map of pear using SNPs integrated with
SSRs, developed by the rapid and robust technology of restriction-associated DNA
sequencing (RADseq). The linkage map consists of 3143 SNP markers and 98 SSRs,
3241 markers in total, spanning 2243.4 cM, with an average marker distance of
0.70 cM. Anchoring SSRs were able to anchor seventeen linkage groups to their
corresponding chromosomes. Based on this high-density integrated pear linkage map
and two years of fruit phenotyping, a total of 32 potential QTLs for 11 traits,
including length of pedicel (LFP), single fruit weight (SFW), soluble solid
content (SSC), transverse diameter (TD), vertical diameter (VD), calyx status
(CS), flesh colour (FC), juice content (JC), number of seeds (NS), skin colour
(SC), and skin smooth (SS), were identified and positioned on the genetic map.
Among them, some important fruit-related traits have for the first time been
identified, such as calyx status, length of pedicel, and flesh colour, and
reliable localization of QTLs were verified repeatable. This high-density linkage
map of pear is a worthy reference for mapping important fruit traits, QTL
identification, and comparison and combination of different genetic maps.
PMID- 25129130
TI - A network perspective on nitrogen metabolism from model to crop plants using
integrated 'omics' approaches.
AB - Nitrogen (N), as an essential element in amino acids, nucleotides, and proteins,
is a key factor in plant growth and development. Omics approaches such as
metabolomics and transcriptomics have become a promising way to inspect complex
network interactions in N metabolism and can be used for monitoring the uptake
and regulation, translocation, and remobilization of N. In this review, the
authors highlight recent progress in omics approaches, including transcript
profiling using microarrays and deep sequencing, and show recent technical
developments in metabolite profiling for N studies. Further, network analysis
studies including network inference methods with correlations, information
theoretic measures, and a network concept to examine gene expression clusters in
relation to N regulatory systems in plants are introduced, and integrating
network inference methods and integrated networks using multiple omics data are
discussed. Finally, this review summarizes recent omics application examples
using metabolite and/or transcript profiling analysis to elucidate the regulation
of N metabolism and signalling and the coordination of N and carbon metabolism in
model plants (Arabidopsis and rice), crops (tomato, maize, and legumes), and
trees (Populus).
PMID- 25129129
TI - SRR1 is essential to repress flowering in non-inductive conditions in Arabidopsis
thaliana.
AB - Timing of flowering is determined by environmental and developmental signals,
leading to promotion or repression of key floral integrators. SENSITIVITY TO RED
LIGHT REDUCED (SRR1) is a pioneer protein previously shown to be involved in
regulation of the circadian clock and phytochrome B signalling in Arabidopsis
thaliana. This report has examined the role of SRR1 in flowering time control.
Loss-of-function srr1-1 plants flowered very early compared with the wild type
under short-day conditions and had a weak flowering response to increasing
daylength. Furthermore, FLOWERING LOCUS T (FT) transcript levels were elevated
already in short days in srr1-1 compared with the wild type. This correlated with
elevated end of day levels of CONSTANS (CO), whereas levels of CYCLING DOF FACTOR
1 (CDF1), a repressor of CO transcription, were reduced. srr1-1 gi-2 and srr1-1
co-9 double mutants showed that SRR1 can also repress flowering independently of
the photoperiodic pathway. srr1-1 flowered consistently early between 16 degrees
C and 27 degrees C, showing that SRR1 prevents premature flowering over a wide
temperature range. SRR1 also promotes expression of the repressors TEMPRANILLO 1
(TEM1) and TEM2. Consequently their targets in the gibberellin biosynthesis
pathway were elevated in srr1-1. SRR1 is thus an important focal point of both
photoperiodic and photoperiod-independent regulation of flowering. By stimulating
expression of the FT-binding repressors CDF1, TEM1 and TEM2, and FLC, flowering
is inhibited in non-inductive conditions.
PMID- 25129132
TI - Nitrogen control of developmental phase transitions in Arabidopsis thaliana.
AB - Nitrogen (N) is an essential macronutrient and a key structural component of
macromolecules in plants. N nutrients and metabolites can act as signals that
impact on many aspects of plant biology. The plant life cycle involves a series
of developmental phase transitions that must be tightly coordinated to external
and internal cues in order to ensure plant survival and reproduction. N
availability is one of the factors controlling phase changes. In this review, we
integrate and summarize the known effects of N over different developmental
stages in plants. Substantial advances have been made in our understanding of
signalling and N-responsive gene regulatory networks. We focus on the molecular
mechanisms underlying N regulation of developmental transitions and the role of
putative new regulators that might link N availability to pathways controlling
Arabidopsis growth and development from seed germination through the plant
reproductive transition.
PMID- 25129131
TI - Insights into transcriptional regulation of beta-D-N-acetylhexosaminidase, an N
glycan-processing enzyme involved in ripening-associated fruit softening.
AB - Tomato (Solanum lycopersicum) fruit ripening-specific N-glycan processing enzyme,
beta-D-N-acetylhexosaminidase (beta-Hex), plays an important role in the ripening
associated fruit-softening process. However, the regulation of fruit ripening
specific expression of beta-Hex is not well understood. We have identified and
functionally characterized the fruit ripening-specific promoter of beta-Hex and
provided insights into its transcriptional regulation during fruit ripening. Our
results demonstrate that RIPENING INHIBITOR (RIN), a global fruit ripening
regulator, and ABSCISIC ACID STRESS RIPENING 1 (SlASR1), a poorly characterized
ripening-related protein, are the transcriptional regulators of beta-Hex. Both
RIN and SlASR1 directly bound to the beta-Hex promoter fragments containing CArG
and C2-3(C/G)A cis-acting elements, the binding sites for RIN and SlASR1,
respectively. Moreover, beta-Hex expression/promoter activity in tomato fruits
was downregulated once expression of either RIN or SlASR1 was suppressed;
indicating that RIN and SlASR1 positively regulate the transcription of beta-Hex
during fruit ripening. Interestingly, RIN could also bind to the SlASR1 promoter,
which contains several CArG cis-acting elements, and SlASR1 expression was
suppressed in rin mutant fruits, indicating that RIN also acts as a positive
regulator of SlASR1 expression during fruit ripening. Taken together, these
results suggest that RIN, both directly and indirectly, through SlASR1, regulates
the transcription of beta-Hex during fruit ripening. The fruit ripening-specific
promoter of beta-Hex could be a useful tool in regulating gene expression during
fruit ripening.
PMID- 25129134
TI - The development of differences in hospital costs accross income groups in Finland
from 1998 to 2010.
AB - OBJECTIVE: To quantify differences in hospital costs between socioeconomic groups
and the development over time. METHODS: Register data on somatic specialised
hospital admissions for patients aged between 25 and 84 in Finland in 1998-2010
were used with income data individually linked to them. The cost of an admission
was calculated by multiplying the number of a patient's inpatient days by the
inpatient day cost of the patient's DRG. We calculated age-standardised admission
costs per resident and per user as well as costs per inpatient day and
concentration indices separately for men and women. RESULTS: Hospital admission
costs reduced with increasing income. The difference between the extreme income
quintiles was more than 50% throughout the study period, and this difference
widened. However, the cost per inpatient day was more than 20% higher in the
highest income group. The differences between income groups were the most
prominent in disease categories involving surgery. CONCLUSIONS: The growth
between socioeconomic groups in hospital costs is presumably mainly due to
increasing differences in morbidity. More attention needs to be paid to
prevention of health inequalities and access to and content of primary care among
low-income groups in order to decrease the need for hospitalisations.
PMID- 25129135
TI - Perspectives of physicians practicing in low and middle income countries towards
generic medicines: a narrative review.
AB - OBJECTIVES: This review was conducted to document published literature related to
physicians' knowledge, attitudes, and perceptions of generic medicines in low-
and middle-income countries (LMICs) and to compare the findings with high-income
countries. METHODS: A systematic search of articles published in peer-reviewed
journals from January 2001 to February 2013 was performed. The search comprised
nine electronic databases. The search strategy involved using Boolean operators
for combinations of the following terms: generic medicines, generic medications,
generic drugs, generic, generic substitution, generic prescribing, international
non-proprietary, prescribers, doctors, general practitioners, physicians, and
specialists. RESULTS: Sixteen articles were included in this review. The majority
(n=11) were from high income countries and five from LMICs. The main difference
between high income countries and LMICs is that physicians from high income
countries generally have positive views whereas those from LMICs tend to have
mixed views regarding generic medicines. Few similarities were identified among
different country income groups namely low level of physicians' knowledge of the
basis of bioequivalence testing, cost of generic medicines as an encouraging
factor for generic medicine prescribing, physicians' concerns towards safety and
quality of generic medicines and effect of pharmaceutical sales representative on
generic medicine prescribing. CONCLUSION: The present literature review revealed
that physicians from LMICs tend to have mixed views regarding generic medicines.
This may be due to differences in the health care system and pharmaceutical
funding system, medicine policies, the level of educational interventions, and
drug information sources in countries of different income levels.
PMID- 25129133
TI - Small RNAs as important regulators for the hybrid vigour of super-hybrid rice.
AB - Heterosis is an important biological phenomenon; however, the role of small RNA
(sRNA) in heterosis of hybrid rice remains poorly described. Here, we performed
sRNA profiling of F1 super-hybrid rice LYP9 and its parents using high-throughput
sequencing technology, and identified 355 distinct mature microRNAs and trans
acting small interfering RNAs, 69 of which were differentially expressed sRNAs
(DES) between the hybrid and the mid-parental value. Among these, 34 DES were
predicted to target 176 transcripts, of which 112 encoded 94 transcription
factors. Further analysis showed that 67.6% of DES expression levels were
negatively correlated with their target mRNAs either in flag leaves or panicles.
The target genes of DES were significantly enriched in some important biological
processes, including the auxin signalling pathway, in which existed a regulatory
network mediated by DES and their targets, closely associated with plant growth
and development. Overall, 20.8% of DES and their target genes were significantly
enriched in quantitative trait loci of small intervals related to important rice
agronomic traits including growth vigour, grain yield, and plant architecture,
suggesting that the interaction between sRNAs and their targets contributes to
the heterotic phenotypes of hybrid rice. Our findings revealed that sRNAs might
play important roles in hybrid vigour of super-hybrid rice by regulating their
target genes, especially in controlling the auxin signalling pathway. The above
finding provides a novel insight into the molecular mechanism of heterosis.
PMID- 25129136
TI - Sodium pentaborate pentahydrate and pluronic containing hydrogel increases
cutaneous wound healing in vitro and in vivo.
AB - After a disruption of skin integrity, the body produces an immediate response
followed by a functional and comparable regeneration period, referred to as wound
healing. Although normal wounds do not need much attention during the healing
period, chronic (non-healing) wounds are the major challenge of current
dermatological applications. Therefore, developing new, safe, and effective wound
healing drugs has always been an attractive area of international research. In
the current study, sodium pentaborate pentahydrate (NaB), pluronics (Plu; F68 and
F127), and their combinations were investigated for their wound healing
activities, using in vitro and in vivo approaches. The results revealed that NaB
significantly increased migration capacity and superoxide dismutase activity in
primary human fibroblasts. Combinations of optimized concentrations for pluronic
block co-polymers further increased cell migration, and the messenger RNA (mRNA)
expression levels of important growth factor and cytokines (vascular endothelial
growth factor (VEGF), transforming growth factor beta (TGF-beta), and tumor
necrosis factor alpha (TNF-alpha)). NaB containing hydrogel co-formulated with
pluronics was also investigated for their wound healing activities using a full
thickness wound model in rats. Macroscopic and histopathological analysis
confirmed that wounds in combination gel-treated groups healed faster than those
of control groups. NaB/Plu gel application was found to increase wound
contraction and collagen deposition in the wound area. Therefore, our results
suggest that NaB, and its pluronics combination, could be used in dermatological
clinics and be a future solution for chronic wounds. However, further studies
should be conducted to explore its exact action of mechanism and effects of this
formulation on chronic wounds.
PMID- 25129137
TI - Selenium deficiency inhibits the conversion of thyroidal thyroxine (T4) to
triiodothyronine (T3) in chicken thyroids.
AB - Selenium (Se) influences the metabolism of thyroid hormones in mammals. However,
the role of Se deficiency in the regulation of thyroid hormones in chickens is
not well known. In the present study, we examined the levels of thyroidal
triiodothyronine (T3), thyroidal thyroxine (T4), free triiodothyronine, free
thyroxine (FT4), and thyroid-stimulating hormone in the serum and the mRNA
expression levels of 25 selenoproteins in chicken thyroids. Then, principal
component analysis (PCA) was performed to analyze the relationships between the
selenoproteins. The results indicated that Se deficiency influenced the
conversion of T4 to T3 and induced the accumulation of T4 and FT4. In addition,
the mRNA expression levels of the selenoproteins were generally decreased by Se
deficiency. The PCA showed that eight selenoproteins (deiodinase 1 (Dio1), Dio2,
Dio3, thioredoxin reductase 2 (Txnrd2), selenoprotein i (Seli), selenoprotein u
(Selu), glutathione peroxidase 1 (Gpx1), and Gpx2) have similar trends, which
indicated that they may play similar roles in the metabolism of thyroid hormones.
The results showed that Se deficiency inhibited the conversion of T4 to T3 and
decreased the levels of the crucial metabolic enzymes of the thyroid hormones,
Dio1, Dio2, and Dio3, in chickens. In addition, the decreased selenoproteins
(Dio1, Dio2, Dio3, Txnrd2, Seli, Selu, Gpx1, and Gpx2) induced by Se deficiency
may indirectly limit the conversion of T4 to T3 in chicken thyroids. The
information presented in this study is helpful to understand the role of Se in
the thyroid function of chickens.
PMID- 25129138
TI - Just like a circus: the public consumption of sex differences.
AB - The study of sex differences is a rich, productive area of neuroscience, yielding
findings that inform our understanding of basic biology and hold promise for
clinical applications. There is a tremendous, problematic mismatch, however,
between the actual implications of this research and what has generally been
communicated to the public. The message communicated by the media, popular press,
and in some cases researchers is often inaccurate with respect to what can and
cannot be concluded from the data. This misrepresentation of findings has led to
a crisis in public education and threatens to do the same in public health. Here,
I suggest a number of ways that neuroscientists might address this growing
problem. First, we should acknowledge that the term 'sex difference' is usually
interpreted by the media and the public as evidence for dichotomous categories
that do not actually exist. Because data rarely sort so cleanly into sex-specific
categories, clearer presentation of the nature and size of sex differences is
warranted. The term 'sex effect' may be preferable to 'sex difference' when the
effect is not large. Second, factors that covary with sex, particularly
experience, should be considered as causes of sex differences before the idea of
"hardwiring" is invoked. Finally, we should be more vigilant about how our own
findings are conveyed to policymakers and the public and speak out when they are
misrepresented.
PMID- 25129139
TI - Physiological correlates of psychopathy, antisocial personality disorder,
habitual aggression, and violence.
AB - This chapter reviews the existing literature on physiological correlates of
psychopathy, antisocial personality disorder, and persistent violence/aggression.
Coverage is provided of findings from studies utilizing peripheral,
electrocortical, and neuroimaging measures. The review begins with a discussion
of how psychopathy and antisocial personality are defined, and how these
conditions relate to one another and to violent behavior. A case is made that the
relationships psychopathy and ASPD show with violent and aggressive behavior, and
similarities and differences in associations of each with physiological measures
of various types can be understood in terms of symptomatic features these
conditions have in common versus features that distinguish them. Following this,
an overview is provided of major lines of evidence emerging from
psychophysiological and neuroimaging studies conducted to date on these
conditions. The final section of the chapter summarizes what has been learned
from these existing studies and discusses implications and directions for future
research.
PMID- 25129140
TI - Connectivity measurements for network imaging.
AB - Communication across the brain networks is dependent on neuronal oscillations.
Detection of the synchronous activation of neurons can be used to determine the
well-being of the connectivity in the human brain networks. Well-connected highly
synchronous activity can be measured by MEG, EEG, fMRI, and PET and then analyzed
with several types of mathematical algorithms. Coherence is one mathematical
method that can detect how well 2 or more sensors or brain regions have similar
oscillatory activity with each other. Phase synchrony can be used to determine if
these oscillatory activities are in sync or out of sync with each other.
Correlation is used to determine the strength of interaction between two
locations or signals. Granger causality can be used to determine the direction of
the information flow in the neuronal brain networks. Statistical analysis can be
performed on the connectivity results to verify evidence of normal or abnormal
network activity in a patient.
PMID- 25129141
TI - Results of a comparative study analyzing octogenarians with renal cell carcinoma
in a competing risk analysis with patients in the seventh decade of life.
AB - OBJECTIVES: To analyze clinicopathological features and survival of surgically
treated patients with renal cell carcinoma (RCC) >= 80 years of age in comparison
with patients between the ages of 60 and 70 years. MATERIALS AND METHODS: The
data for 2,516 patients with a median follow-up of 57 months were retrieved from
a multinational database (Collaborative Research on Renal Neoplasms Association
[CORONA]), including data for 6,234 consecutive patients with RCC after radical
or partial nephrectomy. Comparative analysis of clinicopathological features of
241 octogenarians (3.9% of the database) and 2,275 reference patients between the
ages of 60 and 70 years (36.5%) was performed. Multivariable regression analysis
adjusted for competing risks was applied to identify the effect of advanced age
on cancer-specific mortality (CSM) and other-cause mortality (OCM). Furthermore,
instrumental variable analysis was employed to reduce residual confounding by
unmeasured parameters. RESULTS: Significantly more women were present (50% vs.
40%, P = 0.004), and significantly less often nephron-sparing surgery was
performed in octogenarians compared with the reference group (11% vs. 20%,
P<0.001). Although median tumor size and stages did not significantly defer,
older patients less often had advanced or metastatic disease (N+/M1) (4.6% vs.
9.6%, P = 0.009). On multivariable analysis, higher CSM (hazard ratio = 1.48, P =
0.042) and OCM rates (hazard ratio = 4.32, P<0.001) were detectable in
octogenarians (c-indices = 0.85 and 0.72, respectively). Integration of the
variable age group in multivariable models significantly increased the predictive
accuracy regarding OCM (6%, P<0.001), but not for CSM. Limitations are based on
the retrospective study design. CONCLUSIONS: Octogenarian patients with RCC
significantly differ in clinical features and display significantly higher CSM
and OCM rates in comparison with their younger counterparts.
PMID- 25129142
TI - Predictors of 30-day acute kidney injury following radical and partial
nephrectomy for renal cell carcinoma.
AB - INTRODUCTION: Patients with renal cell carcinoma who were treated with radical
nephrectomy (RN) or partial nephrectomy (PN) are at risk of postoperative acute
kidney injury (AKI), and in consequence, short- and long-term adverse outcomes.
We sought to identify independent predictors of 30-day AKI in patients undergoing
RN or PN. MATERIALS AND METHODS: Between 2005 and 2011, patients who underwent RN
or PN for renal cell carcinoma within the National Surgical Quality Improvement
Program data set were identified. Patients with preexisting severe renal failure,
defined as a preoperative estimated glomerular filtration rate<30 ml/min/1.73
m(2), were excluded from the analyses. AKI was defined as an elevation of serum
creatinine>2mg/dl above baseline or the need for dialysis within 30 days of
surgery. Univariable and multivariable logistic regression analyses were used to
examine the association between preoperative factors and the risk of
postoperative AKI. RESULTS: Overall, 1,944 (58.6%) and 1,376 (41.4%) patients
underwent RN and PN, respectively. Overall, 1.8% of the patients included in the
study experienced AKI within an average of 5.4 days after RN or PN. Independent
predictors for AKI included obesity (odds ratio [OR] = 2.24, P = 0.04), history
of neurovascular disease (OR = 5.29, P<0.001), and a preoperative chronic kidney
disease stage II (OR = 10.00, P = 0.03) or stage III (OR = 26.49, P = 0.02).
Furthermore, RN (OR = 2.87, P = 0.02) or the open approach (OR = 2.18, P = 0.04)
was significantly associated with postoperative AKI. AKI was significantly
associated with adverse postoperative outcomes, such as prolonged length of stay,
occurrence of any complication, and mortality (all P <0.001). CONCLUSIONS: The
assessment of preoperative kidney function and comorbidity status is essential to
identify patients at risk of postoperative AKI. In addition to preoperative
chronic kidney disease stages II and III, neurovascular disease, obesity, and
surgical approach (RN or open) represent predictors of 30-day AKI. Careful
patient selection as well as preoperative planning may help reduce this
unfavorable postoperative outcome.
PMID- 25129143
TI - Human somatic cell mutagenesis creates genetically tractable sarcomas.
AB - Creating spontaneous yet genetically tractable human tumors from normal cells
presents a fundamental challenge. Here we combined retroviral and transposon
insertional mutagenesis to enable cancer gene discovery starting with human
primary cells. We used lentiviruses to seed gain- and loss-of-function gene
disruption elements, which were further deployed by Sleeping Beauty transposons
throughout the genome of human bone explant mesenchymal cells. De novo tumors
generated rapidly in this context were high-grade myxofibrosarcomas. Tumor
insertion sites were enriched in recurrent somatic copy-number aberration regions
from multiple cancer types and could be used to pinpoint new driver genes that
sustain somatic alterations in patients. We identified HDLBP, which encodes the
RNA-binding protein vigilin, as a candidate tumor suppressor deleted at 2q37.3 in
greater than one out of ten tumors across multiple tissues of origin. Hybrid
viral-transposon systems may accelerate the functional annotation of cancer
genomes by enabling insertional mutagenesis screens in higher eukaryotes that are
not amenable to germline transgenesis.
PMID- 25129144
TI - JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital
neutropenia.
AB - The analysis of individuals with severe congenital neutropenia (SCN) may shed
light on the delicate balance of factors controlling the differentiation,
maintenance and decay of neutrophils. We identify 9 distinct homozygous mutations
in the JAGN1 gene encoding Jagunal homolog 1 in 14 individuals with SCN. JAGN1
mutant granulocytes are characterized by ultrastructural defects, a paucity of
granules, aberrant N-glycosylation of multiple proteins and increased incidence
of apoptosis. JAGN1 participates in the secretory pathway and is required for
granulocyte colony-stimulating factor receptor-mediated signaling. JAGN1 emerges
as a factor that is necessary in the differentiation and survival of neutrophils.
PMID- 25129145
TI - Jagunal homolog 1 is a critical regulator of neutrophil function in fungal host
defense.
AB - Neutrophils are key innate immune effector cells that are essential to fighting
bacterial and fungal pathogens. Here we report that mice carrying a hematopoietic
lineage-specific deletion of Jagn1 (encoding Jagunal homolog 1) cannot mount an
efficient neutrophil-dependent immune response to the human fungal pathogen
Candida albicans. Global glycobiome analysis identified marked alterations in the
glycosylation of proteins involved in cell adhesion and cytotoxicity in Jagn1
deficient neutrophils. Functional analysis confirmed marked defects in neutrophil
migration in response to Candida albicans infection and impaired formation of
cytotoxic granules, as well as defective myeloperoxidase release and killing of
Candida albicans. Treatment with granulocyte/macrophage colony-stimulating factor
(GM-CSF) protected mutant mice from increased weight loss and accelerated
mortality after Candida albicans challenge. Notably, GM-CSF also restored the
defective fungicidal activity of bone marrow cells from humans with JAGN1
mutations. These data directly identify Jagn1 (JAGN1 in humans) as a new
regulator of neutrophil function in microbial pathogenesis and uncover a
potential treatment option for humans.
PMID- 25129148
TI - Influence of transgenic rice expressing a fused Cry1Ab/1Ac protein on frogs in
paddy fields.
AB - As genetic engineering in plants is increasingly used to control agricultural
pests, it is important to determine whether such transgenic plants adversely
affect non-target organisms within and around cultivated fields. The cry1Ab/1Ac
fusion gene from Bacillus thuringiensis (Bt) has insecticidal activity and has
been introduced into rice line Minghui 63 (MH63). We evaluated the effect of
transgenic cry1Ab/1Ac rice (Huahui 1, HH1) on paddy frogs by comparing HH1 and
MH63 rice paddies with and without pesticide treatment. The density of tadpoles
in rice fields was surveyed at regular intervals, and Cry1Ab/1Ac protein levels
were determined in tissues of tadpoles and froglets collected from the paddy
fields. In addition, Rana nigromaculata froglets were raised in purse nets placed
within these experimental plots. The survival, body weight, feeding habits, and
histological characteristics of the digestive tract of these froglets were
analyzed. We found that the tadpole density was significantly decreased
immediately after pesticide application, and the weight of R. nigromaculata
froglets of pesticide groups was significantly reduced compared with no pesticide
treatment, but we found no differences between Bt and non-Bt rice groups.
Moreover, no Cry1Ab/1Ac protein was detected in tissue samples collected from 192
tadpoles and froglets representing all four experimental groups. In addition, R.
nigromaculata froglets raised in purse seines fed primarily on stem borer and non
target insects, and showed no obvious abnormality in the microstructure of their
digestive tracts. Based on these results, we conclude that cultivation of
transgenic cry1Ab/1Ac rice does not adversely affect paddy frogs.
PMID- 25129147
TI - A genetic mechanism for Tibetan high-altitude adaptation.
AB - Tibetans do not exhibit increased hemoglobin concentration at high altitude. We
describe a high-frequency missense mutation in the EGLN1 gene, which encodes
prolyl hydroxylase 2 (PHD2), that contributes to this adaptive response. We show
that a variant in EGLN1, c.[12C>G; 380G>C], contributes functionally to the
Tibetan high-altitude phenotype. PHD2 triggers the degradation of hypoxia
inducible factors (HIFs), which mediate many physiological responses to hypoxia,
including erythropoiesis. The PHD2 p.[Asp4Glu; Cys127Ser] variant exhibits a
lower K(m) value for oxygen, suggesting that it promotes increased HIF
degradation under hypoxic conditions. Whereas hypoxia stimulates the
proliferation of wild-type erythroid progenitors, the proliferation of
progenitors with the c.[12C>G; 380G>C] mutation in EGLN1 is significantly
impaired under hypoxic culture conditions. We show that the c.[12C>G; 380G>C]
mutation originated ~8,000 years ago on the same haplotype previously associated
with adaptation to high altitude. The c.[12C>G; 380G>C] mutation abrogates
hypoxia-induced and HIF-mediated augmentation of erythropoiesis, which provides a
molecular mechanism for the observed protection of Tibetans from polycythemia at
high altitude.
PMID- 25129149
TI - Soil surface colonization by phototrophic indigenous organisms, in two contrasted
soils treated by formulated maize herbicide mixtures.
AB - Soil phototrophic microorganisms, contributors to soil health and food webs,
share their particular metabolism with plants. Current agricultural practices
employ mixtures of pesticides to ensure the crops yields and can potentially
impair these non-target organisms. However despite this environmental reality,
studies dealing the susceptibility of phototrophic microorganisms to pesticide
mixtures are scarce. We designed a 3 months microcosm study to assess the
ecotoxicity of realistic herbicide mixtures of formulated S-metolachlor (Dual
Gold Safeneur((r))), mesotrione (Callisto((r))) and nicosulfuron (Milagro((r)))
on phototrophic communities of two soils (Limagne vertisol and Versailles
luvisol). The soils presented different colonizing communities, with diatoms and
chlorophyceae dominating communities in Limagne soil and cyanobacteria and
bryophyta communities in Versailles soil. The results highlighted the strong
impairment of Dual Gold Safeneur((r)) treated microcosms on the biomass and the
composition of both soil phototrophic communities, with no resilience after a
delay of 3 months. This study also excluded any significant mixture effect on
these organisms for Callisto((r)) and Milagro((r)) herbicides. We strongly
recommend carrying on extensive soil studies on S-metolachlor and its commercial
formulations, in order to reconsider its use from an ecotoxicological point of
view.
PMID- 25129151
TI - Management of pediatric and adolescent adnexal masses by gasless laparoendoscopic
single-site surgery.
AB - OBJECTIVE: To evaluate the safety and feasibility of gasless transumbilical
laparoendoscopic single-site (LESS) surgery for the management of adnexal masses
in pediatric and adolescent girls aged 19 years or younger. STUDY DESIGN:
Retrospective study of 28 pediatric and adolescent girls each undergoing gasless
LESS surgery and gasless multiport laparoscopic surgery for adnexal masses. In
each case, laparoscopic surgery was performed by the abdominal-wall lift method
under endotracheal general anesthesia. The two groups were compared for their
patient demographics and surgical outcome measures. RESULTS: In the LESS surgery
group, median age of the patients including three pre-menarcheal girls was 17.5
years. The most common symptom was abdominal pain. Median tumor diameter in the
LESS surgery group was 7.4cm. There were no statistical differences in clinical
features between LESS surgery and multiport laparoscopic surgery groups. In the
LESS surgery group, adnexal masses were managed by unilateral cystectomy (n=20),
unilateral salpingo-oophorectomy (n=5), bilateral cystectomy (n=2), and
unilateral salpingectomy (n=1). Emergency LESS surgery was performed for seven
cases due to adnexal torsion and one case due to cyst rupture. Preservation of
affected ovary was not achieved in three emergency cases with adnexal torsion due
to severe necrosis, and in one case each of recurrent mucinous cystadenoma and
huge mucinous cystadenoma. In 24 adnexal masses from 22 girls who received
adnexal cystectomy by LESS surgery, LESS-assisted extracorporeal cystectomy, was
possible in 14 masses while intracorporeal cystectomy was required in other 10.
In a case of dermoid cyst managed by LESS-assisted extracorporeal cystectomy,
additional hemostasis was required by intracorporeal suturing due to laceration
of utero-ovarian ligament. Median-excised tissue weight in the LESS surgery group
was 111g. Significant differences between LESS surgery and multiport laparoscopic
surgery groups were not noted in surgical outcomes and pathological diagnosis,
except for significantly lower C-reactive protein value on postoperative day 3 in
the LESS surgery group. CONCLUSION: Gasless LESS surgery for pediatric and
adolescent adnexal masses is a safe and feasible alternative to multiport
laparoscopic surgery.
PMID- 25129150
TI - Evaluation of single-port laparoscopy for peritoneal carcinomatosis assessment in
advanced ovarian cancer.
AB - OBJECTIVES: Ovarian cancers are usually diagnosed at an advanced stage. The
extent of the disease before surgery partly determines the ability to perform a
complete cytoreduction. The peritoneal cancer index (PCI) is used to evaluate
peritoneal carcinomatosis and has been validated in ovarian cancer and correlated
with resectability. The aim of our study was to assess the feasibility of single
port laparoscopy (SPL) for suspicion of advanced ovarian cancer and to describe
the ability to calculate the PCI score at the time of laparoscopy. STUDY DESIGN:
Between February 2011 and January 2013, 33 patients underwent SPL for suspected
advanced ovarian cancer. Individual records for all patients were prospectively
reviewed and analyzed. For each patient, we determined the PCI score. RESULTS: 33
patients underwent initial SPL, 85% had increased carcinological markers and 67%
a radiological suspicion of peritoneal carcinomatosis. The median operative time
was 90min. During SPL, 76% of patients underwent ascites evacuation; all patients
had peritoneal cytology and peritoneal biopsies. Only 3 patients experienced
perioperative complications. Two open conversions were recorded. Quotation of the
PCI score was possible for all patients. Eighteen patients (55%) had a PCI score
below 10; one had a maximal PCI score of 39. The PCI score was null for 9
patients. Non-browsing areas marked 8 procedures. CONCLUSIONS: SPL appeared to be
feasible, with satisfying immediate results and postoperative outcome, compared
to conventional laparoscopy. It allowed a satisfying exploration of the abdomino
pelvic cavity and a good description of peritoneal carcinomatosis with only a few
non-browsing PCI areas.
PMID- 25129152
TI - Obstetric and perinatal outcomes of twin pregnancies conceived following IVF/ICSI
treatment compared with spontaneously conceived twin pregnancies.
AB - OBJECTIVE: Twin pregnancy is associated with increased obstetric and perinatal
risk. There are conflicting reports on whether assisted conception (ART) further
increases these risks. The aim of this study is to assess the obstetric and
perinatal outcomes of twin pregnancies according to mode of conception. STUDY
DESIGN: A retrospective study of all viable dichorionic-diamniotic (DCDA) twin
pregnancies (n=539) delivered at Cork University Maternity Hospital, Ireland
between 2009 and 2012, divided according to spontaneous conception (SC) and ART
conception, specifically IVF or ICSI. RESULTS: The ART conceived group were on
average 4 years older (36.8+/-4.23 vs 32.3+/-4.93 years) and more frequently
nulliparous (73.7%; n=126 vs 36.1%; n=133) than their SC counterparts (p<0.001).
There was no significant difference in maternal antenatal complications. ART
twins were twice as likely to be delivered by caesarean section (CS) (OR 2.35;
95% CI 1.76-3.14). There was no significant difference in the rates of preterm
birth or NICU admission according to mode of conception. ART conceived twins were
almost twice as likely to be delivered moderately preterm (32-33(+6)) (OR 1.98,
95% CI 1.21-3.23) and were more likely to have RDS and neonatal hypoglycaemia
CONCLUSIONS: Twin pregnancy, irrespective of mode of conception, carries an
increased risk of morbidity and mortality for both mother and babies and
therefore couples should be counselled regarding the increased risk of iatrogenic
twinning associated with double embryo transfer. However, for those that do
conceive twins, they can be advised that assisted conception conveys no
significant disadvantage over naturally conceived twin pregnancies.
PMID- 25129153
TI - Predictive value of combined serum biomarkers for adverse pregnancy outcomes.
AB - OBJECTIVE: To determine if a combination of first and second trimester serum
biomarkers (pregnancy-associated plasma protein A (PAPP-A), free betahCG, and
maternal serum alpha-fetoprotein (msAFP)) may be utilized to develop a predictive
model for adverse pregnancy outcomes. STUDY DESIGN: We conducted a retrospective
analysis including all women who delivered at our institution between 2007 and
2010. We estimated the area under the ROC curve (AUC) to compare predictive
abilities of PAPP-A, free betahCG, and msAFP singularly, and in combination for
adverse pregnancy outcomes. We sought to predict the risks of preeclampsia,
preterm delivery (PTD, <37 weeks gestational age) and low birth weight (LBW,
<2500g). Using logistic regression analysis, we created models that controlled
for maternal age, race, parity, body mass index, and histories of chronic
hypertension and tobacco use. RESULTS: The final sample included 2199 women.
Determining the AUC and optimal cutoff probability values for each of the
biomarkers, we found that for PTD and LBW, the combination of all three
biomarkers was most predictive, while for preeclampsia the combination of msAFP
and PAPP-A was most predictive. The AUC of the three biomarker combination to
detect adverse pregnancy outcomes are as follows: LBW 67%, PTD 72%, and
preeclampsia 77%. We created race-specific logistic regression models to predict
the risk probabilities. To illustrate, the predictive probability for a 33-year
old African American, nullipara with a BMI of 50, chronic hypertension, tobacco
use, PAPP-A 0.3, msAFP 2.0 and free betahCG 0.98 MOMs are: PTD 59%, LBW 61% and
Preeclampsia 91%. CONCLUSION: The combination of biomarkers currently utilized in
Down syndrome screening may also be used to predict additional adverse pregnancy
outcomes. Further studies are needed to determine optimal maternal and fetal
surveillance, if and when increased risks are identified.
PMID- 25129154
TI - Personal birth preferences and actual mode of delivery outcomes of obstetricians
and gynaecologists in South West England; with comparison to regional and
national birth statistics.
AB - OBJECTIVE: To determine personal birth preferences of obstetricians in various
clinical scenarios, in particular elective caesarean section for maternal
request. To determine actual rates of modes of deliveries amongst the same group.
To compare the obstetrician's mode of delivery rates, to the general population.
STUDY DESIGN: Following ethical approval, a piloted online survey link was sent
via email to 242 current obstetricians and gynaecologists, (consultants and
trainees) in South West England. Mode of delivery results were compared to
regional and national population data, using Hospital Episode Statistics and
subjected to statistical analysis. RESULTS: The response rate was 68%. 90% would
hypothetically plan a vaginal delivery, 10% would consider a caesarean section in
an otherwise uncomplicated primiparous pregnancy. Of the 94/165 (60%) respondents
with children (201 children), mode of delivery for the first born child; normal
vaginal delivery 48%, caesarean section 26.5% (elective 8.5%, emergency 18%),
instrumental 24.5% and vaginal breech 1%. Only one chose an elective caesarean
for maternal request. During 2006-2011 obstetricians have the same overall actual
modes of birth as the population (p=0.9). CONCLUSIONS: Ten percent of
obstetricians report they would consider requesting caesarean section for
themselves/their partner, which is the lowest rate reported within UK studies.
However only 1% actually had a caesarean solely for maternal choice. When
compared to regional/national statistics obstetricians currently have modes of
delivery that are not significantly different than the population and suggests
that they choose non interventional delivery if possible.
PMID- 25129146
TI - Joint analysis of three genome-wide association studies of esophageal squamous
cell carcinoma in Chinese populations.
AB - We conducted a joint (pooled) analysis of three genome-wide association studies
(GWAS) of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese
ancestry (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058
controls for follow-up. In a logistic regression model adjusted for age, sex,
study and two eigenvectors, two new loci achieved genome-wide significance,
marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence
interval (CI) = 0.82-0.88; P = 7.72 * 10(-20)) and rs1642764 at 17p13.1 (per
allele OR = 0.88, 95% CI = 0.85-0.91; P = 3.10 * 10(-13)). rs7447927 is a
synonymous SNP in TMEM173, and rs1642764 is an intronic SNP in ATP1B2, near TP53.
Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved
genome-wide significance in the two populations at highest risk for ESSC (OR =
1.33, 95% CI = 1.22-1.46; P = 1.99 * 10(-10)). Our joint analysis identifies new
ESCC susceptibility loci overall as well as a new locus unique to the population
in the Taihang Mountain region at high risk of ESCC.
PMID- 25129155
TI - Atmospheric pollutants in fog and rain events at the northwestern mountains of
the Iberian Peninsula.
AB - Atmospheric polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls
(PCBs) are persistent organic pollutants (POPs) and exist in gas and particle
phases, as well as dissolved or suspended in precipitation (fog or rain). While
the hydrosphere is the main reservoir for PAHs, the atmosphere serves as the
primary route for global transport of PCBs. In this study, fog and rain samples
were collected during fourteen events from September 2011 to April 2012 in the
Xistral Mountains, a remote range in the NW Iberian Peninsula. PAH compounds
[especially of low molecular weight (LMW)] were universally found, but mainly in
the fog-water samples. The total PAH concentration in fog-water ranged from non
detected to 216 ng.L(-1) (mean of 45 ng.L(-1)), and was much higher in fall than
in winter. Total PAH levels in the rain and fog events varied from non-detected
to 1272 and 33 ng.L(-1) for, respectively, LMW and high molecular weight (HMW)
PAHs. Diagnostic ratio analysis (LMW PAHs/HMW PAHs) suggested that petroleum
combustion was the dominant contributor to PAHs in the area. Total PCB levels in
the rain and fog events varied from non-detected to 305 and 91 ng.L(-1) for,
respectively, PCBs with 2-3 Cl atoms and 5-10 Cl atoms. PCBs, especially those
with 5-10 Cl atoms, were found linked to rain events. The occurrence of the most
volatile PCBs, PCBs with 2-3 Cl atoms, is related to wind transport from far away
sources, whereas the occurrence of PCBs with 5-10 Cl atoms seems to be related
with the increase of its deposition during rainfall at the end of summer and
fall. The movement of this fraction of PCBs is facilitated by its binding to air
suspended particles, whose concentrations usually show an increase as the result
of a prolonged period of drought in summer.
PMID- 25129156
TI - Arsenic species in raw and cooked rice: implications for human health in rural
Bengal.
AB - This study compares the concentrations of total and different species of arsenic
(As) in 29 pairs of raw and cooked rice samples collected from households in an
area of West Bengal affected by endemic arsenicism. The aim is to investigate the
effects of indigenous cooking practice of the rural villagers on As accumulation
and speciation in cooked rice. It is found that inorganic As is the predominant
species in both raw (93.8%) and cooked rice (88.1%). Cooking of rice with water
low in As (<10 MUg L(-1)) significantly decreases the total and inorganic As
content in cooked rice compared to raw rice. Arsenic concentration is mainly
decreased during boiling of rice grains with excess water. Washing of rice grains
with low As water has negligible effect on grain As concentration. The study
suggests that rice cooking with low As water by the villagers is a beneficial
risk reduction strategy. Despite reductions in As content in cooked rice because
of cooking with low As water, the consumption of cooked rice represents a
significant health threat (in terms of chronic As toxicity) to the study
population.
PMID- 25129157
TI - The sub-lethal effects and tissue concentration of the human pharmaceutical
atenolol in rainbow trout (Oncorhynchus mykiss).
AB - Atenolol is a highly prescribed anti-hypertensive pharmaceutical and a member of
the group of beta-blockers. It has been detected at concentrations ranging from
ng L(-1) to low MUg L(-1) in waste and surface waters. The present study aimed to
assess the sub-lethal effects of atenolol on rainbow trout (Oncorhynchus mykiss)
and to determine its tissue-specific bioconcentration. Juvenile rainbow trout
were exposed for 21 and 42 days to three concentration levels of atenolol (1 MUg
L(-1) - environmentally relevant concentration, 10 MUg L(-1), and 1000 MUg L(
1)). The fish exposed to 1 MUg L(-1) atenolol exhibited a higher lactate content
in the blood plasma and a reduced haemoglobin content compared with the control.
The results show that exposure to atenolol at concentrations greater than or
equal to 10 MUg L(-1) significantly reduces both the haematocrit value and the
glucose concentration in the blood plasma. The activities of the studied
antioxidant enzymes (catalase and superoxide dismutase) were not significantly
affected by atenolol exposure, and only the highest tested concentration of
atenolol significantly reduced the activity of glutathione reductase. The
activities of selected CYP450 enzymes were not affected by atenolol exposure. The
histological changes indicate that atenolol has an effect on the vascular system,
as evidenced by the observed liver congestion and changes in the pericardium and
myocardium. Atenolol was found to have a very low bioconcentration factor (the
highest value found was 0.27). The bioconcentration levels followed the order
liver>kidney>muscle. The concentration of atenolol in the blood plasma was below
the limit of quantification (2.0 ng g(-1)). The bioconcentration factors and the
activities of selected CYP450 enzymes suggest that atenolol is not metabolised in
the liver and may be excreted unchanged.
PMID- 25129158
TI - Mercury in organisms from the Northwestern Mediterranean slope: importance of
food sources.
AB - Mercury (Hg) is a global threat for marine ecosystems, especially within the
Mediterranean Sea. The concern is higher for deep-sea organisms, as the Hg
concentration in their tissues is commonly high. To assess the influence of food
supply at two trophic levels, total Hg concentrations and carbon and nitrogen
stable isotope ratios were determined in 7 species (4 teleosts, 2 sharks, and 1
crustacean) sampled on the upper part of the continental slope of the Gulf of
Lions (Northwestern Mediterranean Sea), at depths between 284 and 816 m. Mean Hg
concentrations ranged from 1.30+/-0.61 to 7.13+/-7.09 MUg g(-1) dry mass, with
maximum values observed for small-spotted catshark Scyliorhinus canicula. For all
species except blue whiting Micromesistius poutassou, Hg concentrations were
above the health safety limits for human consumption defined by the European
Commission, with a variable proportion of the individuals exceeding limits (from
23% for the Norway lobster Nephrops norvegicus to 82% for the blackbelly rosefish
Helicolenus dactylopterus). Measured concentrations increased with increasing
trophic levels. Carbon isotopic ratios measured for these organisms demonstrated
that settling phytoplanktonic organic matter is not only the main source fueling
trophic webs but also the carrier of Hg to this habitat. Inter- and intraspecific
variations of Hg concentrations revealed the importance of feeding patterns in Hg
bioaccumulation. In addition, biological parameters, such as growth rate or
bathymetric range explain the observed contamination trends.
PMID- 25129159
TI - Defining fish community structure in Lake Winnipeg using stable isotopes
(delta(13)C, delta(15)N, delta(34)S): implications for monitoring ecological
responses and trophodynamics of mercury & other trace elements.
AB - The ecological integrity of freshwater lakes is influenced by atmospheric and
riverine deposition of contaminants, shoreline development, eutrophication, and
the introduction of non-native species. Changes to the trophic structure of Lake
Winnipeg, Canada, and consequently, the concentrations of contaminants and trace
elements measured in tissues of native fishes, are likely attributed to
agricultural runoff from the 977,800 km(2) watershed and the arrival of non
native zooplankters and fishes. We measured delta(13)C, delta(15)N, and
delta(34)S along with concentrations of 15 trace elements in 17 native fishes
from the north and south basins of Lake Winnipeg in 2009 and 2010. After
adjusting for differences in isotopic baseline values between the two basins,
fishes in the south basin had consistently higher delta(13)C and delta(34)S, and
lower delta(15)N. We found little evidence of biomagnification of trace elements
at the community level, but walleye (Sander vitreus) and freshwater drum
(Aplodinotus grunniens) had higher mercury and selenium concentrations with
increased trophic position, coincident with increased piscivory. There was
evidence of growth dilution of cobalt, copper, manganese, molybdenum, thallium,
and vanadium, and bioaccumulation of mercury, which could be explained by
increases in algal (and consequently, lake and fish) productivity. We conclude
that the north and south basins of Lake Winnipeg represent very different
communities with different trophic structures and trace element concentrations.
PMID- 25129161
TI - Accumulation and elimination of polychlorinated dibenzo-p-dioxins and
dibenzofurans in mule ducks.
AB - In Taiwan, a food safety crisis involving a presence of high concentrations of
dioxin residues in duck eggs occurred in 2004. The dioxin content in duck meat
sampled from supermarkets was also reported to be substantially higher than in
products from other farm animals. Despite increased awareness of the potential
for contamination and exposure to dioxins, the accumulation and elimination of
dioxins in ducks have not been well characterized. In the present study, mule
ducks were fed capsules containing polychlorinated dibenzo-p-dioxins and
dibenzofurans (PCDD/Fs) for 14 days and the trial was continued for another 28
days without PCDD/Fs supplementation. Ducks were sacrificed on the 14th, 28th,
and 42nd days from the beginning of administration and samples of abdominal fat,
breast, and liver tissue were obtained. The concentrations of PCDD/Fs were
analyzed in the samples to investigate their distribution and elimination in
various duck tissues. The bioaccumulation of PCDD/Fs in ducks was found to be
tissue-dependent. In the abdominal fat, the bioconcentration factor was
negatively correlated with the degree of chlorination. Conversely, more
chlorinated PCDD/Fs (hexa- or hepta-congeners) were associated with higher
bioconcentration in the liver and breast tissue. In terms of the efficiency of
PCDD/Fs elimination, the liver was found to be the fastest, followed by the
breast and the abdominal fat. The clearance rate positively correlated with the
degree of chlorination, as determined by comparing the apparent elimination rate
constant (k) of PCDD/Fs in various tissues. Overall, lower k values observed in
this study imply that mule ducks have a reduced clearance of PCDD/Fs in
comparison with layer and broiler chickens.
PMID- 25129160
TI - Remediation of petroleum hydrocarbon-contaminated sites by DNA diagnosis-based
bioslurping technology.
AB - The application of effective remediation technologies can benefit from adequate
preliminary testing, such as in lab-scale and Pilot-scale systems. Bioremediation
technologies have demonstrated tremendous potential with regards to cost, but
they cannot be used for all contaminated sites due to limitations in biological
activity. The purpose of this study was to develop a DNA diagnostic method that
reduces the time to select contaminated sites that are good candidates for
bioremediation. We applied an oligonucleotide microarray method to detect and
monitor genes that lead to aliphatic and aromatic degradation. Further, the
bioremediation of a contaminated site, selected based on the results of the
genetic diagnostic method, was achieved successfully by applying bioslurping in
field tests. This gene-based diagnostic technique is a powerful tool to evaluate
the potential for bioremediation in petroleum hydrocarbon contaminated soil.
PMID- 25129162
TI - Distribution, sources and composition of antibiotics in sediment, overlying water
and pore water from Taihu Lake, China.
AB - The occurrence of 15 antibiotics classified as sulphonamides, fluoroquinolones,
macrolides, tetracyclines and trimethoprim in sediment, overlying water, and pore
water matrices in Taihu Lake, China was studied. The total concentrations were
from 4.1 MUg/kg to 731 MUg/kg, from 127 ng/L to 1210 ng/L, and from 1.5 ng/L to
216 ng/L in sediment, overlying water and pore water, respectively. Antibiotics
in different locations originated from various sources, depending on human,
agricultural and aquacultural activities. Composition analysis indicated that
human-derived and animal-derived drugs significantly contributed to the total
contamination of antibiotics in the lake, indicating the high complexity of
contamination sources in Taihu Lake Basin. The in situ sediment-pore water
partitioning coefficients were generally greater than sediment-overlying water
partitioning coefficients, suggesting continuous inputs into the lake water. This
study shows that antibiotics are ubiquitous in all compartments in Taihu Lake,
and their potential hazards to the aquatic ecosystem need further investigation.
PMID- 25129163
TI - Trends of ambient fine particles and major chemical components in the Pearl River
Delta region: observation at a regional background site in fall and winter.
AB - In the fall and winter of 2007 to 2011, 167 24-h quartz filter-based fine
particle (PM2.5) samples were collected at a regional background site in the
central Pearl River Delta. The PM2.5 showed an annual reduction trend with a rate
of 8.58 MUg m(-3) (p<0.01). The OC component of the PM2.5 reduced by 1.10 MUg m(
3) yr(-1) (p<0.01), while the reduction rates of sulfur dioxide (SO2) and sulfate
(SO4(2-)) were 10.2 MUg m(-3) yr(-1) (p<0.01) and 1.72 MUg m(-3) yr(-1) (p<0.01),
respectively. In contrast, nitrogen oxides (NOx) and nitrate (NO(3-)) presented
growth trends with rates of 6.73 MUg m(-3) yr(-1) (p<0.05) and 0.79 MUg m(-3) yr(
1) (p<0.05), respectively. The PM2.5 reduction was mainly related to the decrease
of primary OC and SO4(2-), and the enhanced conversion efficiency of SO2 to SO4(2
) was related to an increase in the atmospheric oxidizing capacity and a decrease
in aerosol acidity. The discrepancy between the annual trends of NOx and NO3(-)
was attributable to the small proportion of NO3(-) in the total nitrogen budget.
CAPSULE ABSTRACT: Understanding annual variations of PM2.5 and its chemical
composition is crucial in enabling policymakers to formulate and implement
control strategies on particulate pollution.
PMID- 25129164
TI - Intraluminal lesion of the pulmonary artery: A diagnostic challenge.
PMID- 25129165
TI - Workplace accidents, absenteeism and productivity in patients with sleep apnea.
AB - INTRODUCTION: Obstructive sleep apnea-hypopnea syndrome (OSAHS) has health
related outcomes, but the impact of OSAHS on occupational health has been
scarcely studied. The aim of this study was to evaluate the effect of OSAHS on
workplace accidents, absenteeism and productivity. METHOD: One hundred eighty-two
OSAHS patients and 71 healthy subjects completed the Epworth Sleepiness Scale,
the Pittsburgh Sleep Quality Index and the Spanish IMPALA (Impact of Disease on
Work Productivity) index and answered various questions on workplace accidents
and sick leave. Participants were classified to an OSAHS group or a non-OSAHS
group according to polysomnography results. RESULTS: Patients with OSAHS had more
sick leave lasting longer than 30days (16.6% vs. 7%, P=.049) and lower
productivity (63.80% vs. 83.20%, P=.000) than subjects without OSAHS, although
the rate of workplace accidents was similar in both groups (27.4% vs 25.4%;
P>.050). None of the OSAHS-related variables was associated with workplace
accidents. A diagnosis of OSAHS was related with absenteeism. Psychological
distress and OSAHS were related with productivity. CONCLUSIONS: OSAHS causes
limitations in the working lives of patients and leads to a higher incidence of
sick leave and lower productivity. A diagnosis of OSAHS was the variable with
most influence on the working lives of patients.
PMID- 25129166
TI - A comparison of optimisation methods and knee joint degrees of freedom on muscle
force predictions during single-leg hop landings.
AB - The aim of this paper was to compare the effect of different optimisation methods
and different knee joint degrees of freedom (DOF) on muscle force predictions
during a single legged hop. Nineteen subjects performed single-legged hopping
manoeuvres and subject-specific musculoskeletal models were developed to predict
muscle forces during the movement. Muscle forces were predicted using static
optimisation (SO) and computed muscle control (CMC) methods using either 1 or 3
DOF knee joint models. All sagittal and transverse plane joint angles calculated
using inverse kinematics or CMC in a 1 DOF or 3 DOF knee were well-matched (RMS
error<3 degrees ). Biarticular muscles (hamstrings, rectus femoris and
gastrocnemius) showed more differences in muscle force profiles when comparing
between the different muscle prediction approaches where these muscles showed
larger time delays for many of the comparisons. The muscle force magnitudes of
vasti, gluteus maximus and gluteus medius were not greatly influenced by the
choice of muscle force prediction method with low normalised root mean squared
errors (<48%) observed in most comparisons. We conclude that SO and CMC can be
used to predict lower-limb muscle co-contraction during hopping movements.
However, care must be taken in interpreting the magnitude of force predicted in
the biarticular muscles and the soleus, especially when using a 1 DOF knee.
Despite this limitation, given that SO is a more robust and computationally
efficient method for predicting muscle forces than CMC, we suggest that SO can be
used in conjunction with musculoskeletal models that have a 1 or 3 DOF knee joint
to study the relative differences and the role of muscles during hopping
activities in future studies.
PMID- 25129167
TI - Investigation of impact loading rate effects on the ligamentous cervical spinal
load-partitioning using finite element model of functional spinal unit C2-C3.
AB - The cervical spine functions as a complex mechanism that responds to sudden
loading in a unique manner, due to intricate structural features and kinematics.
The spinal load-sharing under pure compression and sagittal flexion/extension at
two different impact rates were compared using a bio-fidelic finite element (FE)
model of the ligamentous cervical functional spinal unit (FSU) C2-C3. This model
was developed using a comprehensive and realistic geometry of spinal components
and material laws that include strain rate dependency, bone fracture, and
ligament failure. The range of motion, contact pressure in facet joints, failure
forces in ligaments were compared to experimental findings. The model
demonstrated that resistance of spinal components to impact load is dependent on
loading rate and direction. For the loads applied, stress increased with loading
rate in all spinal components, and was concentrated in the outer intervertebral
disc (IVD), regions of ligaments to bone attachment, and in the cancellous bone
of the facet joints. The highest stress in ligaments was found in capsular
ligament (CL) in all cases. Intradiscal pressure (IDP) in the nucleus was
affected by loading rate change. It increased under compression/flexion but
decreased under extension. Contact pressure in the facet joints showed less
variation under compression, but increased significantly under flexion/extension
particularly under extension. Cancellous bone of the facet joints region was the
only component fractured and fracture occurred under extension at both rates. The
cervical ligaments were the primary load-bearing component followed by the IVD,
endplates and cancellous bone; however, the latter was the most vulnerable to
extension as it fractured at low energy impact.
PMID- 25129168
TI - Challenges towards the elimination of Human African Trypanosomiasis in the
sleeping sickness focus of Campo in southern Cameroon.
AB - The sleeping sickness focus of Campo lies along the Atlantic coast and extends
along the Ntem River, which constitutes the Cameroonian and Equatorial Guinean
border. It is a hypo-endemic focus with the disease prevalence varying from 0.3
to 0.86% during the last few decades. Investigations on animal reservoirs
revealed a prevalence of Trypanosoma brucei gambiense of 0.6% in wild animals and
4.83% in domestic animals of this focus. From 2001 to 2012, about 19 931 tsetse
were collected in this focus and five tsetse species including Glossina palpalis
palpalis, G. pallicera, G. nigrofusca, G. tabaniformis and G. caliginea were
identified. The analysis of blood meals of these flies showed that they feed on
human, pig, goat, sheep, and wild animals such as antelope, duiker, wild pig,
turtle and snake. The percentage of blood meals taken on these hosts varies
according to sampling periods. For instance, 6.8% of blood meals from pig were
reported in 2004 and 22% in 2008. This variation is subjected to considerable
evolutions because the Campo HAT focus is submitted to socio-economic mutations
including the reopening of a new wood company, the construction of autonomous
port at "Kribi" as well as the dam at "Memve ele". These activities will bring
more that 3000 inhabitants around Campo and induce the deforestation for the
implementation of farmlands as well as breeding of domestic animals. Such
mutations have impacts on the transmission and the epidemiology of sleeping
sickness due to the modification of the fauna composition, the nutritional
behavior of tsetse, the zoophilic/anthropophilic index. To achieve the
elimination goal in the sleeping sickness focus of Campo, we report in this paper
the current epidemiological situation of the disease, the research findings of
the last decades notably on the population genetics of trypanosomes, the
modifications of nutritional behavior of tsetse, the prevalence of T. b.
gambiense in humans, domestic and wild animals. An overview on the types of
mutations occurring in the region has been raised and a discussion on the
strategies that can be implemented to achieve the elimination of the disease has
been made.
PMID- 25129169
TI - Sulfonamide inhibition study of the carbonic anhydrases from the bacterial
pathogen Porphyromonas gingivalis: the beta-class (PgiCAb) versus the gamma-class
(PgiCA) enzymes.
AB - The oral pathogenic bacterium Porphyromonas gingivalis, encodes for two carbonic
anhydrases (CAs, EC 4.2.1.1) one belonging to the gamma-class (PgiCA) and another
one to the beta-class (PgiCAb). This last enzyme has been cloned and
characterized here for its inhibition profile with the main class of CA
inhibitors, the sulfonamides. Many of the clinically used sulfonamides as well as
simple aromatic/heterocyclic sulfonamides were ineffective as PgiCAb inhibitors
whereas better inhibition was observed with simple derivatives such as
sulfanilamide, metanilamide, 4-aminoalkylbenzenesulfonamides (KIs of 364-475nM).
The halogenosulfanilamides incorporating heavy halogens, 4-hydroxy- and 4
hydroxyalkyl-benzenesulfonamides, were also micromolar, ineffective PgiCAb
inhibitors. The best inhibitors of the beta-class enzyme were acetazolamide and
ethoxzolamide, with KIs of 214-280nM. Interestingly, the gamma-class enzyme was
much more sensitive to sulfonamide inhibitors compared to the beta-class one,
PgiCAb. Identification of potent and possibly selective inhibitors of
PgiCAb/PgiCA may lead to pharmacological tools useful for understanding the
physiological role(s) of these enzymes, since this bacterium is the main
causative agent of periodontitis and few treatment options are presently
available.
PMID- 25129170
TI - 'Carba'-carfentanil (trans isomer): a MU opioid receptor (MOR) partial agonist
with a distinct binding mode.
AB - There is strong evidence to indicate that a positively charged nitrogen of
endogenous and exogenous opioid ligands forms a salt bridge with the Asp residue
in the third transmembrane helix of opioid receptors. To further examine the role
of this electrostatic interaction in opioid receptor binding and activation, we
synthesized 'carba'-analogues of the highly potent MU opioid analgesic
carfentanil (3), in which the piperidine nitrogen was replaced with a carbon. The
resulting trans isomer (8b) showed reduced, but still significant MOR binding
affinity (Ki(MU)=95.2nM) with no MOR versus DOR binding selectivity and was a MOR
partial agonist. The cis isomer (8a) was essentially inactive. A MOR docking
study indicated that 8b bound to the same binding pocket as parent 3, but its
binding mode was somewhat different. A re-evaluation of the uncharged morphine
derivative N-formylnormorphine (9) indicated that it was a weak MOR antagonist
showing no preference for MOR over KOR. Taken together, the results indicate that
deletion of the positively charged nitrogen in MU opioid analgesics reduces MOR
binding affinity by 2-3 orders of magnitude and may have pronounced effects on
the intrinsic efficacy and on the opioid receptor selectivity profile.
PMID- 25129171
TI - Design, synthesis, biological evaluation of substituted benzofurans as DNA
gyraseB inhibitors of Mycobacterium tuberculosis.
AB - DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase and is
a well-established and validated target for the development of novel
therapeutics. By adapting the medium throughput screening approach, we present
the discovery and optimization of ethyl 5-(piperazin-1-yl) benzofuran-2
carboxylate series of mycobacterial DNA gyraseB inhibitors, selected from Birla
Institute of Technology and Science (BITS) database chemical library of about
3000 molecules. These compounds were tested for their biological activity; the
compound 22 emerged as the most active potent lead with an IC50 of 3.2+/-0.15MUM
against Mycobacterium smegmatis DNA gyraseB enzyme and 0.81+/-0.24MUM in MTB
supercoiling activity. Subsequently, the binding of the most active compound to
the DNA gyraseB enzyme and its thermal stability was further characterized using
differential scanning fluorimetry method.
PMID- 25129172
TI - Comorbidity of psychiatric disorders with Internet addiction in a clinical
sample: the effect of personality, defense style and psychopathology.
AB - This study aims to contribute to the understanding of underlying causes for the
development of Internet Addiction Disorder (IAD) and assess comorbidity with
other mental disorders through the analysis of data from a clinical sample of
college students who presented for treatment of IAD. The clinical sample of our
study has demonstrated a high percentage of comorbidity with Axis I and II
disorders, while the temporal precedence of the establishment of those disorders
cannot lead to specific conclusions. Half of the sample (25/50) presented with
comorbidity of another Axis I disorder and 38% (19/50) with a concurrent Axis II
personality disorder. The majority of Axis I disorders (51.85%) were reported
before the onset of IAD, 33.3% after the onset while it was unclear in 14.81% of
cases. The examination of a path model demonstrated that important contributions
to the understanding of this disorder can be made through concepts from the
neurobiological, trait personality paradigm, as well as from the psychodynamic
defense style paradigm. Comorbid psychopathology can further exacerbate the
presentation of IAD through a direct link, regardless of the underlying
personality structure. The clinician treating IAD patients should complete a
clinical evaluation for comorbid Axis I and II diagnoses since their presence may
signify a more serious presentation.
PMID- 25129174
TI - Emergency department triage. Why and how?
PMID- 25129173
TI - Correlates of use of electronic cigarettes versus nicotine replacement therapy
for help with smoking cessation.
AB - INTRODUCTION: Electronic- or e-cigarettes are nicotine-delivery devices commonly
used by smokers to quit or reduce smoking. At present, not much is known about
the characteristics of smokers who specifically try e-cigarettes to quit smoking
compared to the nicotine replacement therapy (NRT) products approved by the U.S.
Food and Drug Administration (FDA). Determining the characteristics of smokers
who are likely to choose e-cigarettes as cessation aids would help develop
strategies to impart valid information about e-cigarettes to such smokers as
facts regarding the safety and utility of e-cigarettes emerge. METHODS: This
study is based on 834 daily smokers [mean age=45.8 (standard deviation=13)] from
Hawaii. Demographic, smoking- and cessation-related variables were examined as
correlates of ever use of e-cigarette only or any FDA-approved NRT product only
or both as cessation aids. RESULTS: Results indicated that younger smokers, non
White smokers, and smokers reporting higher income, lower nicotine dependence,
shorter smoking history, and higher lifetime quit attempts were more likely to
have tried e-cigarettes but not NRT products for help with smoking cessation.
CONCLUSION: Smokers who are attracted to use e-cigarettes but not FDA-approved
NRT products may differ from smokers who are likely to have used NRT products but
not e-cigarettes in terms of demographic (e.g., age, ethnicity) and smoking- or
cessation-related characteristics (e.g., nicotine dependence, quit attempts).
Given the lack of knowledge regarding the health effects of e-cigarettes and
their efficacy as cessation aids, future research needs to continue
characterizing smokers who are likely to use e-cigarettes for smoking cessation.
PMID- 25129175
TI - Update in the management of allergic fungal sinusitis.
AB - Over the last 3 decades, allergic fungal sinusitis (AFS) has been defined as a
clinically and pathologically distinct form of chronic rhinosinusitis. The
etiology, pathogenesis, and natural history of the disease has not been fully
understood, and the appropriate treatment for AFS is also controversial. The
management of AFS includes a combination of functional endoscopic sinus surgery
and medical treatment in the form of pre- and post-operative systemic steroids,
local steroids, and allergic immunotherapy. Close follow-up and coordination
between the surgeon and physician is needed for optimum outcome. Despite
aggressive medical and surgical treatment, high recurrence rates have been
reported. In this review, we study the current literature and data regarding
various surgical and non-surgical treatment options for AFS.
PMID- 25129176
TI - Microribonucleic acids and vascular restenosis.
AB - Microribonucleic acids (miRNAs) are small non-coding RNAs, which control diverse
cellular functions by either promoting degradation or inhibiting target messenger
RNA translation. An aberrant expression profile of miRNAs has been linked to
human diseases, including cardiovascular dysfunction. This review summarizes the
latest insights in the identification of vascular-specific miRNAs and the
underlying mechanisms for their roles in vascular restenosis mainly by
influencing the proliferation and migration of vascular smooth muscle cell. Here,
we discuss miRNA-based drug and gene therapy in vascular restenosis.
PMID- 25129177
TI - Systematic review of quality of care in Saudi Arabia. A forecast of a high
quality health care.
AB - OBJECTIVES: To explore the current structure of the Saudi health care system, and
assess the quality of health care in the Kingdom of Saudi Arabia (KSA) based on
the indicators provided by the Institute of Medicine (IOM), and to provide
recommendations for improvements. METHODS: This study explores the current
structure of the Saudi health care system using a systematic review of studies
published between 2009 and 2013. The IOM indicators of quality health care (safe,
effective, patient-centered, timely, efficient, and equitable) are used to
determine the current quality of healthcare in KSA. Studies that examined the
quality of health care were evaluated for methodological soundness by giving a
quality score based on Russell and Gregory's criteria. RESULTS: The quality of
healthcare in KSA has progressed significantly over the recent years at all
levels of health services. Like many countries, KSA is investing money and
efforts to improve quality of healthcare in the Kingdom. Although significant
progress has been made, barriers affecting this quality are still apparent as the
general population increases, patients' health care needs, and demands are also
rising. Factors affecting the quality of healthcare can be categorized into
patient factors (such as health literacy, access to care, and culture), and
providers' factors (including medical care, workload, culture, and job
satisfaction). CONCLUSION: As a result of these unaddressed issues, the quality
of healthcare in the Kingdom may be degenerating. Additionally, as the population
of KSA has increased and medical technology has become more sophisticated and
costly, and patients' demands and expectations have also increased. Providing
quality healthcare to all patients is a fundamental human right. Poor quality
healthcare causes patient suffering, institutional waste, and misuse of community
resources.
PMID- 25129178
TI - Cytotoxic effect of Salvadora persica extracts on human gingival fibroblast
cells.
AB - OBJECTIVES: To assess the cytotoxic potential of Salvadora persica (S. persica)
extracts on human gingival fibroblast (HGF) cells. METHODS: This study was
conducted between January and May 2012 in collaboration with Dental Caries
Research Chair, College of Dentistry, King Saud University, Riyadh, Saudi Arabia.
Extracts of S. persica using hexane, ethylacetate, and ethanol as solvents at
concentrations of 0.5 mg/ml and 1 mg/ml were evaluated for their cytotoxic
activity against HGFs using the 3 cytotoxic assays: (3-(4,5-Dimethylthiazol-2-yl)
2,5-diphenyltetrazolium bromide, a tetrazole) (MTS), lactic dehydrogenase (LDH),
and crystal violet (CV). International standards for the evaluation of medical
materials recommended cut-off value of cell survival >70% was used for
interpretation of the results. RESULTS: Ethanol extract of S. persica at 0.5
mg/ml and 1 mg/ml and hexane extract of S. persica at 0.5 mg/ml were completely
devoid of cytotoxic activity, hexane extract at 1 mg/ml in comparison with
controls demonstrated some cytotoxicity with cell survival of 88% (p=0.045) in
MTS, 86% (p=0.01) in LDH, and 88% (p=0.002) in CV assays. Similarly, ethyl
acetate extract of S. persica at 0.5 mg/ml maintained cell viability of 91% in
MTS, 81% in LDH, and 80% in CV assays. Maximum cytotoxicity against HGFs was
observed with ethyl acetate extract of S. persica at 1 mg/ml with cell survival
of 60% in MTS, 40% in LDH, and 66% CV assays (p=0.0001). CONCLUSION: The
acceptable level of cytotoxicity associated with S. persica ethanol and hexane
extracts requires further evaluation to be used as irrigation solutions in
endodontic treatment.
PMID- 25129179
TI - Diagnostic clues for spondylitis in acute brucellosis.
AB - OBJECTIVES: To determine the diagnostic factors for brucellar spondylitis.
METHODS: This retrospective study included 227 consecutive brucellosis patients
admitted to the Infectious Diseases and Clinical Microbiology clinics of Adiyaman
State Hospital and Adiyaman 82 nd Year State Hospital, Adiyaman, Turkey between
January 2010 and December 2012. Acute brucellosis was diagnosed by standard tube
agglutination test and/or growth of Brucella spp. in appropriately prepared
culture media (Bactec). Brucellar spondylitis was diagnosed and followed-up with
contrast-enhanced magnetic resonance imaging. RESULTS: Among the 227 brucellosis
patients included, 88 (38.8%) were male, and 139 (61.2%) were female. Brucellar
spondylitis was detected in 54 patients (23.7%). Brucellar spondylitis patients
had higher mean age, higher fever, and higher blood culture positivity rate when
compared with brucellosis patients (p=0.001, p=0.001, and p=0.001). Logistical
regression analysis determined that male gender (OR: 3.006), older age (OR:
1.025), erythrocyte sedimentation rate (ESR) (OR: 1.067), high fever at the time
of admission (OR: 2.550), and positive blood cultures for Brucella spp. (OR:
4.003) values were independently associated with brucellar spondylitis. However,
high C-reactive protein (CRP) levels (OR: 0.971) were not found as a risk factor
for brucellar spondylitis. CONCLUSIONS: The results of this study shows that the
risk of developing brucellar spondylitis is high in patients with acute
brucellosis, who are at advanced age, who have high fever, that have Brucella
spp. growth in their blood culture that has a high ESR value, and who are male.
PMID- 25129180
TI - Ten-year review of invasive Candida infections in a tertiary care center in Saudi
Arabia.
AB - OBJECTIVES: To review the epidemiology of invasive Candida infections in a single
center in Saudi Arabia over a subsequent 10-year period. METHODS: This
retrospective study was carried out in a single center in Saudi Arabia over a 10
year period. Records of all patients with invasive Candida infections (ICI) over
the period from January 2003 to December 2012 were reviewed. Mann-Whitney U test
was used for comparison of Candida albicans (C. albicans) versus non-albicans
Candida species, and fluconazole resistance versus fluconazole susceptible in
relation to crude mortality at 30 days and 90 days. RESULTS: Eight hundred
positive sterile site cultures, associated with 652 ICI were identified. Median
age was 52 years and 53% of patients were males. Candida albicans were the most
common species (38.7%), followed by Candida tropicalis (18.9%), and Candida
glabrata (C. glabrata) (16.3%). The proportion of ICI caused by C. albicans
remained stable over time (p=0.07), but C. glabrata increased significantly
(p<0.001). The median rate of ICI per 1,000 hospital discharges per year was
1.65, with a significant trend towards higher rates over time (p=0.01). Most
isolates were susceptible to fluconazole, voriconazole, and amphotericin B. Only
66.7% of Candida krusei were susceptible to caspofungin. Overall 30-day crude
mortality was 40.6%. There was no significant difference in crude mortality in
association with C. albicans compared with non-albicans species, nor in
association with fluconazole resistance. CONCLUSION: The rate of ICI increased
significantly in the proportion of ICI caused by C. glabrata. Most isolates
remain susceptible to caspofungin, voriconazole, and amphotericin B. The crude
mortality remains high.
PMID- 25129181
TI - Quality of life assessment using the World Health Organization quality
questionnaire pre- and post- otolaryngological surgery among patients in western
Saudi Arabia.
AB - OBJECTIVES: To evaluate the health-related quality of life (HRQoL) of patients'
pre- and post- otolaryngological surgery. METHODS: We conducted a cross-sectional
study of patients who underwent otolaryngological surgery in the western region
of Saudi Arabia between March and October 2013. We administered the Arabic
version of the World Health Organization Quality of Life assessment instrument to
all patients before surgery and 2-4 weeks after surgery. The demographic details
such as age, gender, level of education, marital status, patients' incomes,
otolaryngology diagnosis, and type of otolaryngology surgery were analyzed.
RESULTS: A total of 99 patients (43 males and 52 females), ranging from 1-75
years of age (mean: 21.6 years), were included in this study. The most frequently
diagnosed conditions were chronic tonsillitis and obstructive sleep apnea due to
adenoid enlargement. Adenotonsillectomy was the most frequently performed
surgery, followed by septoplasty and myringotomy with grommet tube insertion. For
all domains, patients had significantly higher scores post-surgery. The highest
score was obtained for the social relationship domain and the lowest for the
physical health domain. However, the highest differences between the pre- and
post- surgery scores were for physical health (7.9), psychological (5.1),
environmental (2.5), and social health (2.3) domains. CONCLUSION: The HRQoL of
patients improved significantly after otolaryngology surgery.
PMID- 25129182
TI - Risk factors for posterior to right recurrent laryngeal nerve lymph node
metastasis in papillary thyroid carcinoma.
AB - OBJECTIVES: To identify the risk factors for posterior right recurrent laryngeal
nerve lymph node metastasis (PRRLN-LNM) in papillary thyroid carcinoma (PTC).
METHODS: We conducted a retrospective study of 389 patients with primary PTC who
underwent right lobectomy or total thyroidectomy, and comprehensive right or
bilateral central compartment dissection (CCD) with or without lateral neck
dissection (LND) between January 2010 and May 2013 at the Department of Head and
Neck Surgery, Institute of Micro-Invasive Surgery of Zhejiang University,
Zhejiang, China. The clinicopathological findings were investigated, and relative
risk factors for PRRLN-LNM were analyzed. RESULTS: Central compartment LNM were
present in 50.9% (198/389), and PRRLN-LNM were present in 12.6% (49/389) of
patients, wherein 3.1% (12/389) had PRRLN-LNM only. A multivariate analysis
revealed that younger age (<= 35 years), extrathyroidal extension (ETE), lateral
compartment LNM, prelaryngeal LNM, pretracheal, and right paratracheal LNM were
independent predictors of PRRLN-LNM. CONCLUSION: This study revealed that younger
age (<= 35 years), ETE, prelaryngeal LNM, lateral compartment LNM, and
pretracheal and right paratracheal lymph nodes (anterior to the right recurrent
laryngeal nerve [level VIa]), LNM were independent factors of PRRLN-LN (level
VIb). Therefore, comprehensive right CCD should be routinely performed for such
patients.
PMID- 25129183
TI - Clinical outcomes of transradial unprotected left main coronary artery stenting
in the elderly.
AB - OBJECTIVES: To evaluate the long-term results in elderly patients undergoing
percutaneous coronary intervention (PCI) with drug-eluting stents for unprotected
left main coronary artery disease by transradial approach. METHODS: This study
took place in Qinhuangdao First Hospital, Hebei Medical University, Hebei, China
between October 2006 and December 2009. Seventy-nine elderly patients with
unprotected left main coronary artery (ULMCA) stenosis, aged >70 years, that
underwent drug-eluting stent were evaluated. The occurrence of major adverse
cardiac events (MACE) (death, non-fatal myocardial infarction, stroke or target
lesion revascularizations) was recorded after 3 years of follow-up. RESULTS:
After 3 years follow-up, the MACE free survival rate was 72.2%. Cardiac deaths
occurred in 7.6% of patients. Myocardial infarction occurred in 5.1%, and target
lesion revascularization in 13.9% of patients. Age and left main distal
bifurcation were favorable predictors of MACE. CONCLUSIONS: Percutaneous coronary
intervention can be performed with good angiographic and clinical results through
a transradial approach in the elderly. The long term survival suggests that PCI
in ULMCA patients >= 70 years is safe and efficacious.
PMID- 25129184
TI - External cephalic version for breech presentation at term. A prospective
interventional study.
AB - OBJECTIVES: To evaluate the external cephalic version (ECV) procedure for the
management of at term breech presenting fetuses. METHODS: In this prospective,
interventional study, 90 patients with uncomplicated breech presentations at or
after 37 weeks' gestation were considered for ECV. This was performed in Al
Batool Teaching Hospital, Mosul, Iraq, between January 2011 and March 2012. The
main outcome measure was assessed as the success rate of ECV attempt and the rate
of cesarean section following a successful procedure. Parity, type of breech,
placental location, and birth weight were evaluated as predictors of success.
Also, any fetal or maternal complications during the procedure were evaluated.
Data were analyzed by x2 test. Statistical significance was determined at a level
of p<0.05. RESULTS: The success rate was 80%. The rate of cesarean section
following successful procedure was only 12.5%. Prognostic parameters associated
with successful ECV were multiparity and flexed type of breech. There were no
serious fetal or maternal complications associated with the attempt. CONCLUSIONS:
With appropriate selection of patients, ECV is highly successful and is a safer
alternative to vaginal breech delivery or cesarean delivery.
PMID- 25129185
TI - Skeletal and dental characteristics of subjects with incompetent lips.
AB - OBJECTIVES: To evaluate the cephalometric features of subjects with incompetent
lips, and to find the most discriminant variables for lip incompetence among the
following: dental protrusion and proclination, antero-posterior and vertical
skeletal relationships, and lip dimensions. METHODS: This retrospective study was
conducted at King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, between
2011 and 2012. Cephalograms of 84 subjects (22 males and 62 females, aged 20.18+/
3.65 years) diagnosed as having incompetent lips were collected (incompetent
group [IG]) and compared with the control group (CG), matching in age and gender
distribution. Thirty-five measurements were compared between the 2 groups using
independent t-test. Stepwise discriminant analysis of lip incompetence was
performed. RESULTS: Compared to the CG, subjects in the IG had thinner upper
lips, shorter upper and lower lips, more retrognathic facial types, greater angle
between nasion-point A and nasion-point B, shorter anterior and posterior cranial
bases, shorter palatal length, shorter mandibular body length, shorter ramal
length, steeper mandibular plane, less prominent chin, bimaxillary dental
protrusion, and smaller inter-incisal angle. The significant discriminant
variables, in order, were inter-incisor angle, inclination of upper incisors,
ramal height, anterior cranial base, palatal plane to Frankfort horizontal plane
angle, lower and then upper anterior dental height, upper lip thickness, and
length. CONCLUSIONS: The presence of incompetent lips can be attributed to more
than one factor and not only bimaxillary protrusion. This should be considered
during the treatment planning of such problem.
PMID- 25129186
TI - A cross sectional study on the acceptance of pre-hospital continuous positive
airway pressure ventilation among ambulance paramedic in an urban emergency
medical service system in a developing country.
AB - OBJECTIVES: To assess the acceptance among the developing country urban
paramedics towards pre-hospital continuous positive airway pressure (CPAP)
ventilation. METHODS: A cross-sectional prospective study was conducted among the
ambulance paramedics working at the pre-hospital care unit of the Universiti
Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia from March 2012 to
August 2012 on ambulance paramedics. Questionnaires were used to assess their
experience, knowledge, and perception, while their competencies were assessed
using an Objective Structured Clinical Examination by 2 independent-calibrated
raters on the use of the Boussignac CPAP system. RESULTS: Twenty-six ambulance
paramedics qualified for this study with an average work experience of 5.59+/
3.53 years. A total of 76.9% had no formal training for CPAP during their study
years. Knowledge of CPAP apparatus-arrangement sequence scored as 88.5% correct,
while 96.2% scored 'Good' to 'Very-good' in the ability to diagnose conditions
that warrant its use. A total of 76.9% were confident to monitor patients on
CPAP, and 61.5% in applying the device. However, only 53.8% were confident to
start the CPAP, and 38.5% to troubleshoot if any problem arose. For perceptions,
96.2% felt it was easy to learn CPAP, while 88.5% felt that paramedics could use
it without supervision, and 80.8% felt that it should not be confined to the
Emergency Department setting. A total of 96.1% were competent in CPAP
application. CONCLUSION: Developing country urban ambulance paramedics possessed
adequate knowledge, positive attitudes, and demonstrated good CPAP application
skills. However, lack of confidence towards decision to initiate and troubleshoot
of potential complications were the main obstacles hindering its use.
PMID- 25129187
TI - Acute hemiplegia as a rare presentation of infantile Guillain-Barre syndrome.
AB - Guillain-Barre syndrome (GBS) usually presents in a symmetrical ascending fashion
of weakness. We present a 6-month-old male infant who presented to our emergency
room with acute left-sided limb weakness and head lag 3 days after a febrile
upper respiratory tract infection. A diagnosis of GBS was established by
confirming high cerebrospinal fluid protein, motor nerve reduced amplitude, and
prolonged conductions, and MRI T2 high signal intensity affecting the ventral
roots of the spinal cord. He showed remarkable clinical and neurophysiological
improvement after intravenous immunoglobulin and intensive physiotherapy. The
occurrence of infantile acute hemiplegia as a presentation of GBS is rare. This
report highlights the importance of considering GBS in the differential diagnosis
so that early effective treatment may be started.
PMID- 25129188
TI - Toe tourniquet syndrome.
AB - Toe tourniquet syndrome refers to external, mechanical, circumferential
constriction of the toes. We report a series of 4 infants with toe tourniquet
syndrome from Saudi Arabia who presented during wintertime with very similar
symptoms (approximately 48 hours of inconsolable crying and irritability),
similar involved region (toes), and similar constricting agent (hairs). Immediate
removal of the hair fibers was carried out in all patients, fortunately followed
by fast healing with no signs of tissue necrosis. The prompt diagnosis and
treatment of the condition were vital in attaining the good outcome and
preventing ischemic complications.
PMID- 25129189
TI - Colon cancer metastasis to the thyroid gland.
AB - Thyroid metastasis originating from colon cancer is an uncommon clinical entity.
We present a case of a 40-year-old Saudi male patient that was known to have
metastatic adenocarcinoma of the colon, and who presented initially with
hoarseness of voice. A left thyroid lesion was found and fine-needle aspiration
biopsy showed that it was a colon cancer metastasis. His condition later
deteriorated with development of stridor. Tracheostomy was performed and the
diagnosis was confirmed by biopsy. A high index of suspicion is required to
consider colorectal carcinoma metastatic to the thyroid.
PMID- 25129190
TI - Minimally invasive endoscopic removal of a massive trabecular juvenile ossifying
fibroma of the paranasal sinuses.
AB - An 11-year-old female patient presented with left-sided nasal obstruction and
upward displacement of the left eye of 3 months duration. Clinical examination
revealed a firm mass in the left nasal cavity. A CT scan showed a massive tumor
involving the left maxillary sinus with extension into the ethmoid sinus, and
encroaching on the left orbit. Histopathological examination revealed trabecular
juvenile ossifying fibroma, which was removed via a transnasal endoscopic surgery
by the Otorhinolaryngology, Head and Neck and the skull base team. She tolerated
the lengthy procedure well, and there was no recurrence postoperatively as the
tumor was resected completely. There was no external scarring and no
psychological trauma discerned.
PMID- 25129191
TI - Nasal chondromesenchymal hamartoma in an adolescent with pleuropulmonary
blastoma.
AB - Nasal chondromesenchymal hamartoma (NCMH) is an extremely rare benign lesion
arising in the sino-nasal tract. They usually affect children below one year of
age. The pathogenesis of these lesions is poorly understood however, they have
been associated with pleuropulmonary blastoma (PPB). Although benign, malignant
transformation has been reported in the literature. On literature review, we
found 32 reported cases, most of them occurring in children below one year. We
report a 14-year-old adolescent male with history of PPB at the age of 6,
presenting with bilateral nasal obstruction and decreased sense of smell. In our
case report we highlight the association between PPB and NCMH, and describe an
unusual presentation.
PMID- 25129192
TI - Direct digital radiograph. Technicians role in obtaining good images.
AB - OBJECTIVES: To determine the rejected rate of direct digital radiography (DRs) in
our hospital, benchmark it with other institutes, and explore the causes of
rejection. METHODS: Data were collected between June 2012 and May 2013 at King
Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia. The rejected
analysis was registered in the system, which is a built in software. Reasons for
rejection could not be deleted, and no further imaging is allowed for the same
patient without reporting the reason for rejection. Reasons for rejection are
predefined by the machine. RESULTS: Of 89,797 images that were acquired, 13,371
were rejected, with a rejection rate of 15%. Positioning errors were the main
reason for rejection, followed by artifact 28.5%, and motion 17.1%. As for body
parts pelvis, abdomen, spine, and knee were recorded as rejected with higher
rates than the average. CONCLUSION: This study has shown a number of unnecessary
repeated imaging of patients. In addition, reject analysis in DR is proven to be
an indicator for quality in imaging, the reasons of rejection that have high
percentage for occurrence should be given more focus during patients scan.
PMID- 25129193
TI - Quality of life among adults with beta-thalassemia major in western Saudi Arabia.
AB - OBJECTIVES: To assess the quality of life in the thalassemia adult patients and
clarify how effective the management is of these patients and whether a change in
care is warranted. METHODS: In this cross-sectional study, adult thalassemia
patients (>18 years) of both genders, attending the day care unit in King
Abdulaziz University Hospital, Jeedah, Saudi Arabia were surveyed using SF-36
questionnaire. Data were collected between October 2012 and December 2012. The
questions highlighted 3 health status scales; physical functioning (PF),
emotional functioning (EF), and social functioning (SF). Scores were analyzed
using SPSS. RESULTS: Forty-eight adults were surveyed (mean+/-SD: 26.02+/-5.56).
These were made up of 60.4% males and 41.7% were Saudis. The frequency of blood
transfusion was every 3 weeks in 81.3% of patients, but 18.8% were having
transfusions less frequently. Half of our sampled patients were splenectomized
(54.2%). The PF score for the total sample was 61.4 (SD=22.7), the SF score was
75 (SD=26.4) and the EF score was 69.7 (SD= 21.6); the SF and EF scores were
lower in females and non-Saudis compared to male Saudis. CONCLUSION: The PF score
in our sample was low compared to other regional studies; the SF and EF scores
were low in females and non-Saudis.
PMID- 25129194
TI - Effects of hyperandrogenism and high body mass index on acne severity in women.
AB - OBJECTIVES: To determine the association between hyperandrogenism and obesity
with acne, and correlation between the severity of acne with the clinical and
laboratory parameters of hyperandrogenism. METHODS: One hundred and forty-one
female with acne vulgaris and 73 healthy women were included in this study. The
correlation of clinical and laboratory signs of hyperandrogenism and the severity
of acne was examined. RESULTS: The prevalence of overweight and obese individuals
in the group with acne was determined significantly higher than the control
group. There was a positive correlation between body mass index (BMI) value and
the severity of acne. The frequency of hirsutism, menstrual irregularity,
androgenetic alopecia, seborrhea and polycystic ovary in the group with acne were
found significantly higher than the control group. The average levels of free
testosterone (fT), total testosterone (TT), dehydroepiandrosteron sulfate, and
prolactine in the groups with acne were found significantly higher compared with
the control group. There was a positive correlation between the fT and TT levels
and the severity of acne. CONCLUSION: The prevalence of hyperandrogenism and
obesity was increased in women with acne. According to the results of our study,
it can be said that circulating androgen levels and BMI play a key role in the
severity of acne.
PMID- 25129195
TI - Unconventional materials and substances used in water pipe (narghile) by smokers
in central western region of Saudi Arabia.
AB - OBJECTIVES: To investigate the use of unconventional substances and materials in
water pipe among cafe water pipe smokers. METHODS: This was a questionnaire-based
survey among subjects attending coffee shops in the region of Al Madinah, Saudi
Arabia between February and March 2013. RESULTS: We invited 110 subjects, only 90
consented to participate in the study. A percentage of 1.1% used fluids other
than water in the water pipe tank, 18.9% added other soft drinks to the tank, and
7.8% added flowers, spices or drugs to the tobacco mix placed in the head of the
water pipe. A proportion of participants used fruits to replace the water pipe
head (12.2%), or to replace water pipe tank (4.4%). Higher number of children the
smokers had and cafe smoking were all significantly associated with
unconventional practices. CONCLUSION: A substantial percentage of sample of water
pipe smokers in Al Madinah, Saudi Arabia use unusual materials and/or substances
in the water pipe and this is probably encouraged by cafe smoking.
PMID- 25129196
TI - Umbilical neoplasm as the first sign of pancreatic adenocarcinoma.
PMID- 25129197
TI - Infection prevention and control guidelines for patients with Middle East
Respiratory Syndrome Coronavirus (MERS-CoV) infection.
PMID- 25129198
TI - Timing of dental development in Saudi cleft lip and palate patients.
PMID- 25129199
TI - Asthma drugs suppress growth.
PMID- 25129200
TI - Longitudinal trajectories of aberrant behavior in fragile X syndrome.
AB - The Aberrant Behavior Checklist-Community (ABC-C; Aman et al., 1995) has been
increasingly adopted as a primary tool for measuring behavioral change in
clinical trials for individuals with fragile X syndrome (FXS). To our knowledge,
however, no study has documented the longitudinal trajectory of aberrant
behaviors in individuals with FXS using the ABC-C. As part of a larger
longitudinal study, we examined scores obtained on the ABC-C subscales for 124
children and adolescents (64 males, 60 females) with FXS who had two or more
assessments (average interval between assessments was approximately 4 years).
Concomitant changes in age-equivalent scores on the Vineland Adaptive Behavior
Scales (VABS) were also examined. As expected for an X-linked genetic disorder,
males with FXS obtained significantly higher scores on all subscales of the ABC-C
and significantly lower age-equivalent scores on the VABS than females with FXS.
In both males and females with FXS, scores on the Irritability/Agitation and
Hyperactivity/Noncompliance subscales of the ABC-C decreased significantly with
age, with little to no change occurring over time on the Lethargy/Social
Withdrawal, Stereotypic Behavior, and Inappropriate Speech subscales. The
decrease in scores on the Hyperactivity/Noncompliance domain was significantly
greater for males than for females. In both males and females, age-equivalent
scores on the VABS increased significantly over this developmental period. These
results establish a basis upon which to evaluate long-term outcomes from
intervention-based research. However, longitudinal direct observational studies
are needed to establish whether the severity of problem behavior actually
decreases over time in this population.
PMID- 25129202
TI - Patterns of habitual physical activity in youth with and without Prader-Willi
Syndrome.
AB - Children classified as overweight or obese and those with disabilities are at a
greater risk of not meeting the minimum recommendation of 60 min a day of
moderate to vigorous physical activity (PA). Youth with Prader-Willi Syndrome
(PWS) appear to participate in less PA compared to nonsyndromal children, likely
due to syndrome-related factors. However, description of PA patterns in youth
with PWS is lacking. The purpose of this study was to characterize PA in youth
with PWS and to compare it to PA in children with nonsyndromal obesity. Twenty
four youth with PWS (ages 8-16 years) and 40 obese children without PWS (OB)
(ages 8-11 years) wore accelerometers for eight consecutive days. Data were
screened for compliance and classified into PA intensities: sedentary behavior
(SED), light (LPA), moderate (MPA), vigorous (VPA) and moderate plus vigorous
(MVPA). Youth with PWS spent 19.4% less time in weekly LPA (p=0.007) and 29.8%
less time in weekly VPA compared to OB controls (p=0.036). All other intensities
were similar between groups. In addition, PWS participated in less LPA and VPA
during the weekends compared to OB, and less LPA on weekdays when compared to OB.
There was also a trend towards PWS participating in less MVPA during the weekends
and less VPA during the weekends than OB controls. There was a trend towards PWS
participating in less VPA on weekends compared to weekdays, while OB participated
similarly in VPA on weekdays and weekend days. On average, neither PWS nor OB
children met minimum MVPA recommendations. The results suggest there is a need to
design exercise programs for PWS youth that focus on integrating vigorous
intensity activities, especially during the weekends when structured PA may not
be available.
PMID- 25129201
TI - Prevalence and factors associated with polypharmacy in Victorian adults with
intellectual disability.
AB - Although polypharmacy is a medication safety concern leading to increased risk of
non-adherence, adverse drug reaction and drug-drug interactions, polypharmacy and
associated risk factors has rarely been investigated involving people with ID at
a population level. The purpose of this paper is to analyze the prevalence of
polypharmacy and to evaluate the role of different factors associated with
polypharmacy in a state-wide representative population of adults with ID. In a
population-based survey in Victoria, Australia, 897 people with ID 18 years of
age or older were selected by simple random sampling. The data were collected
from proxy respondents on behalf of people with ID. Polypharmacy was defined as
the concomitant use of five or more medications. The data were weighted to
reflect the age/sex/geographic distribution of the population. Results revealed
that more than 76% of adults with ID had used prescribed medicine and about 21%
were exposed to polypharmacy in the last two weeks. In both univariate and
multivariate analyses, polypharmacy was significantly associated with older age,
unemployment and inability to get help from family and friends if needed. After
controlling for age, sex and severity of intellectual disability, polypharmacy
was associated with having a blood pressure, blood cholesterol and blood glucose
level check. Polypharmacy was also associated with a greater number of visits to
general practitioners, fair or poor reported health status and inability to walk
unaided. Subjects with epilepsy, diabetes, stroke, osteoporosis and cancer had a
higher probability of polypharmacy. None of the disease inducing behaviors was
associated with polypharmacy. This study highlights the need that medication
should be regularly reviewed overall in ID population and particularly when
polypharmacy exists.
PMID- 25129203
TI - Glomerular nestin expression: possible predictor of outcome of focal segmental
glomerulosclerosis in children.
AB - BACKGROUND: A high prevalence of chronic kidney disease among children with focal
segmental glomerulosclerosis (FSGS) leads to a permanent quest for good
predictors of kidney dysfunction. Thus, we carried out a retrospective cohort
study in order to examine known clinical and morphological predictors of adverse
outcome, as well as to investigate glomerular nestin expression as a potential
new early predictor of kidney dysfunction in children with FSGS. Relationships
between nestin expression and clinical and morphological findings were also
investigated. METHODS: Among 649 renal biopsy samples, obtained from two
children's hospitals, FSGS was diagnosed in 60 children. Thirty-eight patients,
who met the criteria for this study, were followed up for 9.0 +/- 5.2 years.
Using Kaplan-Meier and Cox's regression analysis, potential clinical and
morphological predictors were applied in two models of prediction: after disease
onset and after the biopsy. RESULTS: The present study revealed the following
significant predictors of kidney dysfunction: patients' ages at disease onset, as
well as age at biopsy, resistance to corticosteroid treatment, serum creatinine
level, urine protein/creatinine ratio, vascular involvement, tubular atrophy,
interstitial fibrosis, and decreased glomerular nestin expression. CONCLUSIONS:
The most important finding of our study is that nestin can be used as a potential
new early morphological predictor of kidney dysfunction in childhood onset of
FSGS, since nestin has been obviously decreased in both sclerotic and normal
glomeruli seen by light microscopy.
PMID- 25129204
TI - Serum suPAR levels are modulated by immunosuppressive therapy of minimal change
nephrotic syndrome.
AB - BACKGROUND: Soluble urokinase-type plasminogen activator receptor (suPAR) could
be a causative factor in idiopathic focal segmental glomerulosclerosis (FSGS). It
is currently unknown to what extent suPAR levels could be affected by treatment
with immunosuppressive drugs such as cyclosporin A (CsA) and mycophenolate
mofetil (MMF). Treatment with CsA, but not MMF, is accompanied by nephrotoxicity,
and since suPAR levels correlate with glomerular filtration rate (GFR), treatment
with these drugs could indirectly modulate suPAR levels by their effect on renal
function. METHODS: We measured suPAR levels in a recent prospective multicenter
crossover trial comparing the efficacy of MMF and CsA in pediatric patients with
minimal change disease (MCD) and frequently relapsing steroid-sensitive nephrotic
syndrome (FR-SSNS). All patients had biopsy-proven MCD and normal renal function;
they were treated with each drug for 1 year in a crossover study design. Serum
suPAR levels were measured before and after 1 year of therapy with MMF (n = 40)
and CsA (n = 35). RESULTS: The suPAR levels decreased after 1 year of treatment
with MMF (p < 0.05). Conversely, suPAR levels increased after 1 year of treatment
with CsA in the same patients (p = 0.01). These changes in suPAR levels were not
correlated to the estimated glomerular filtration rate (eGFR) or changes in the
GFR. CONCLUSIONS: Data from this prospective randomized trial suggest that
treatment with MMF and CsA is associated with different effects on suPAR levels
in children with MCD and that these are independent of their effects on GFR.
PMID- 25129205
TI - Central venous catheterization using a perfused human cadaveric model:
application to surgical education.
AB - OBJECTIVE: The purpose of this article is to present a unique training model
using a perfused human cadaver for central line placement training with the
ultimate goal of reducing central venous catheter mechanical complications.
DESIGN: The applicability of the fresh tissue cadaver model for central line
placement was assessed using a 10-item questionnaire with a 5-point Likert-type
scale. Respondents were asked to rate their opinions as strongly agree, agree,
neutral, disagree, or strongly disagree. SETTING: All participants received a
didactic lecture followed by supervised practice on a commercially available
simulator. The students were then relocated to the Fresh Tissue Dissection
Laboratory where they practiced central vein catheterization on a fresh perfused
human cadaver. PARTICIPANTS: Course participants included 87 physicians from
various medical specialties at different stages of training. RESULTS: Results of
the survey demonstrated that 91% of the participating physicians found the
perfused cadaveric model to be a true simulation of conditions that exist in live
patients, and 98% reported that the use of this model promoted acquisition of
technical skills. CONCLUSION: The integration of central line placement training
on perfused cadavers into residency and fellowship training provides an
unparalleled realistic simulation to participants. Further study is needed to
assess whether realistic simulation translates into objective end points such as
decreased mechanical complications.
PMID- 25129206
TI - Post-mortem 7.0-tesla magnetic resonance study of cortical microinfarcts in
neurodegenerative diseases and vascular dementia with neuropathological
correlates.
AB - BACKGROUND: Until recently cortical microinfarcts (CMIs) were considered as the
invisible lesions in clinical-radiological correlation studies that rely on
conventional structural magnetic resonance imaging. The present study
investigates the presence of CMIs on 7.0-T magnetic resonance imaging (MRI) in
post-mortem brains with different neurodegenerative and cerebrovascular diseases.
MATERIALS AND METHODS: One hundred-seventy five post-mortem brains, composed of
37 with pure Alzheimer's disease (AD), 12 with AD associated to cerebral amyloid
angiopathy (AD-CAA), 38 with frontotemporal lobar degeneration, 12 with
amyotrophic lateral sclerosis, 16 with Lewy body disease (LBD), 21 with
progressive supranuclear palsy, 18 with vascular dementia (VaD) and 21 controls
were examined. According to their size several types of CMIs were detected on 3
coronal sections of a cerebral hemisphere with 7.0-T MRI and compared to the mean
CMI load observed on histological examination of one standard separate coronal
section of a cerebral hemisphere at the level of the mamillary body. RESULTS:
Overall CMIs were significantly prevalent in those brains with neurodegenerative
and cerebrovascular diseases associated to CAA compared to those without CAA.
VaD, AD-CAA and LBD brains had significantly more CMIs compared to the controls.
While all types of CMIs were increased in VaD and AD-CAA brains, a predominance
of the smallest ones was observed in the LBD brains. CONCLUSIONS: The present
study shows that 7.0-T MRI allows the detection of several types of MICs and
their contribution to the cognitive decline in different neurodegenerative and
cerebrovascular diseases.
PMID- 25129207
TI - Extrathymic malignancies in a defined cohort of patients with myasthenia gravis.
AB - INTRODUCTION: Myasthenia gravis (MG) may be associated with extrathymic
malignancies, especially in patients with thymoma. AIM: To determine the
frequency and type of extrathymic malignancies in MG patients from the Belgrade
area, and to identify potential risk factors associated with tumors. PATIENTS AND
METHOD: The study comprised 390 patients with MG. Different sociodemographic and
clinical variables potentially associated with extrathymic neoplasms were
analyzed. RESULTS: Extrathymic malignancies were present in 42 (10.8%) MG
patients - 22 (52.4%) males and 20 (47.6%) females. The most frequently detected
were breast (40%) and lung (40%) neoplasms. The tumors appeared with similar
frequency before (45.2%) and after the onset of MG (42.9%). Significant
predictors for the development of extrathymic malignancies were current age (p =
0.001) and immunoglobulin (IVIg) therapy (p = 0.021). On the other hand, current
age (p=0.001), longer MG duration (p = 0.001) and generalized form of MG (p =
0.002) were significant predictors of malignancy occurring after the MG onset.
CONCLUSION: Our study revealed that older MG patients, as well as those with
longer duration of the disease, and those who received IVIg therapy had a higher
oncogenic risk for the development of extrathymic malignancies.
PMID- 25129209
TI - Letter from the guest editors.
PMID- 25129210
TI - Dose tracking and dose auditing in a comprehensive computed tomography dose
reduction program.
AB - Implementation of a comprehensive computed tomography (CT) radiation dose
reduction program is a complex undertaking, requiring an assessment of baseline
doses, an understanding of dose-saving techniques, and an ongoing appraisal of
results. We describe the role of dose tracking in planning and executing a dose
reduction program and discuss the use of the American College of Radiology CT
Dose Index Registry at our institution. We review the basics of dose-related CT
scan parameters, the components of the dose report, and the dose-reduction
techniques, showing how an understanding of each technique is important in
effective auditing of "outlier" doses identified by dose tracking.
PMID- 25129208
TI - Curcumin improves the integrity of blood-spinal cord barrier after compressive
spinal cord injury in rats.
AB - Previous studies have shown that curcumin (Cur) can produce potent
neuroprotective effects against damage due to spinal cord injury (SCI). However,
whether Cur can preserve the function of the blood-spinal cord barrier (BSCB) is
unclear. The present study was performed to investigate the mechanism underlying
BSCB permeability changes, which were induced by treatment with Cur (75, 150, and
300 mg/kg, i.p.) after compressive SCI in rats. BSCB permeability was evaluated
by Evans blue leakage. Motor recovery of rats with SCI was assessed using the
Basso, Beattie, and Bresnahan scoring system every day until the 21st days post
injury. The protein levels of heme oxygenase-1 (HO-1), tight junction protein,
and inflammatory factors were analyzed by western blots. The expression of the
inflammatory factors tumor necrosis factor-alpha (TNF-alpha) and nuclear factor
kappaB (NF-kappaB) mRNA was determined with reverse transcription-polymerase
chain reactions. Treatment with Cur (150 and 300 mg/kg) significantly reduced
Evans blue leakage into the spinal cord tissue at 24h after SCI. Cur (150 mg/kg)
significantly increased HO-1 protein expression. The levels of TNF-alpha and NF
kappaB mRNA and protein greatly increased at 24h after SCI, and this increase was
significantly attenuated by Cur treatment. ZO-1 and occludin expression was
upregulated by Cur (150 mg/kg) treatment after SCI, and this effect was blocked
by the HO-1 inhibitor zinc protoporphyrin. Long-term effects of Cur on motor
recovery after SCI were observed. Our results indicated that Cur can improve
motor function after SCI, which could correlate with improvements in BSCB
integrity.
PMID- 25129211
TI - Magnetic resonance enterography in evaluation and management of children with
Crohn's disease.
AB - The role of radiologic evaluation in Crohn's disease (CD) has undergone a recent
paradigm shift in which the radiologist adds value to the multidisciplinary team
by longitudinally assessing therapeutic response and identifying treatment
modifying subtypes, such as fibrostenotic or fistulizing disease. Magnetic
resonance enterography (MRE) has become the primary imaging modality used. The
combination of multiplanar, multiparametric, and multiphasic contrast-enhanced
imaging with the high spatial resolution and very high tissue contrast of MR
imaging allows for detailed evaluation of intra-abdominal pathology, without the
risk of cumulative radiation exposure. MRE provides the benefit of a complete
evaluation of mural, extramural, and even extraintestinal manifestations and
complications of CD in a single examination. Cine motility sequences and
diffusion-weighted imaging may further increase sensitivity and specificity. MRE
represents an ideal imaging modality for initial evaluation, assessment of
therapeutic response, and evaluation of complications in patients with CD.
PMID- 25129212
TI - Neonatal neurosonography.
AB - Neonatal neurosonography is used commonly to evaluate the central nervous system
in the neonatal intensive care setting. The procedure can be performed at the
bedside in these critically ill patients who may suffer from hemodynamic and
thermoregulatory instability and often require mechanical ventilation. This
article reviews current recommendations regarding neurosonography technique,
pathophysiology, and imaging of intracranial insults including hemorrhage, white
matter injury, infarction, and hypoxic-ischemic encephalopathy.
PMID- 25129213
TI - Techniques that decrease or eliminate ionizing radiation for evaluation of
ventricular shunts in children with hydrocephalus.
AB - Shunted hydrocephalus in children is a commonly seen diagnosis in hospitals
throughout the world and is one of the most common chronic pediatric
neurosurgical conditions. These children undergo numerous studies for routine
surveillance as well as for evaluation of shunt malfunction, many of which are
associated with significant radiation exposure over the child's lifetime. It is
in the child's best interest to minimize the overall exposure to ionizing
radiation so as to decrease the chance of the deleterious effects from occurring.
The article outlines the epidemiology of ventricular shunt catheters, the typical
indications and methods for shunt evaluation, and the preferred alternative
imaging methods that eliminate or reduce radiation exposure.
PMID- 25129214
TI - Pectus excavatum: current imaging techniques and opportunities for dose
reduction.
AB - Pectus excavatum (PE) is the most common congenital chest wall deformity in
children. It affects 1 in every 300-1000 live births with a male to female ratio
of 5:1. Most of the patients present in their first year of life. During the
teenage years, patients may have exercise intolerance and psychological strain
because of their chest wall deformity. The Nuss and Ravitch procedures are
established methods of surgical correction of PE. An index of severity known best
as the Haller index, typically evaluated with computed tomography scan, when
measuring greater than 3.2 is considered to indicate moderate or severe PE and is
a prerequisite for third-party insurance reimbursement for these corrective
procedures. This article reviews the clinical features of PE, the role of
imaging, and the opportunities for radiation dose reduction.
PMID- 25129215
TI - Primary liver tumors in pediatric patients: proper imaging technique for
diagnosis and staging.
AB - Liver tumors in children are rare and comprise a diverse set of both benign and
malignant lesions, most of which are not clinically detected until they are large
and often difficult to resect. Technological advances in diagnostic imaging have
greatly influenced the surgical planning of these lesions and ultimately the
clinical outcome. The intent of this article is to present an imaging algorithm
for the effective and efficient workup of liver tumors in pediatric patients.
This includes the appropriate timing and use of various imaging modalities, such
as conventional radiographs, ultrasound, computed tomography, and magnetic
resonance imaging. This article also addresses the use of sedation, intravenous
contrast agents, and the benefits and limitations of specific imaging modalities.
An overview of the radiologic and pathologic findings in common liver lesions in
pediatric patients, as well as individual case examples demonstrating the use of
the proposed workup algorithm, is provided.
PMID- 25129216
TI - Imaging of nontraumatic acute hip pain in children: multimodality approach with
attention to the reduction of medical radiation exposure.
AB - Nontraumatic acute hip pain in children is common. However, the presentation and
etiology is variable, including difficulty with weight bearing and abnormal gait.
Barriers in communication, multiple possible etiologies, and age-specific
anatomical variations of the pediatric hip make the evaluation of hip pain in
children a difficult clinical diagnosis. Multimodality radiologic approach plays
an important role for the evaluation of these children. However, owing to the
complexity of pediatric hip disease, children sometimes undergo multiple
radiologic examinations, resulting in delay in diagnosis and increased radiation
dose. This article focuses on the illustration and discussion of common causes of
acute hip pain or limp in children. Current recommendations for the imaging of
these patients with specific attention to the ALARA (as low radiation as
reasonably achievable) principle of radiation exposure are considered. Examples
of the entities discussed are provided.
PMID- 25129217
TI - Pediatric interventional radiology and dose-reduction techniques.
AB - The pediatric interventional radiology community has worked diligently in recent
years through education and the use of technology to incorporate numerous dose
reduction strategies. This article seeks to describe different strategies where
we can significantly lower the dose to the pediatric patient undergoing a
diagnostic or therapeutic image-guided procedure and, subsequently, lower the
dose several fold to the staff and ourselves in the process. These strategies
start with patient selection, dose awareness and monitoring, shielding,
fluoroscopic techniques, and collimation. Advanced features such as cone-beam
technology, dose-reduction image processing algorithms, overlay road mapping, and
volumetric cross-sectional hybrid imaging are also discussed.
PMID- 25129218
TI - Imaging of lumps and bumps in pediatric patients: an algorithm for appropriate
imaging and pictorial review.
AB - Superficial lumps and bumps are a common presenting complaint in the pediatric
patient population. Although encountered frequently, the path to a definitive
diagnosis is not always a straightforward one. Imaging offers a valuable tool to
aid in this diagnostic challenge. Radiologists must be familiar with pediatric
lumps and bumps, their imaging characteristics, and the best way to further
evaluate challenging clinical presentations. This will not only allow the
radiologist to serve as a valuable asset to the treating physician in choosing
the most appropriate imaging modality but also help in accurate diagnosis, all
while ensuring the "image gently" principle. An algorithm for imaging in the
pediatric patient with lumps and bumps has been presented in this article and a
few example entities along with their imaging findings have also been reviewed.
PMID- 25129219
TI - Molecular responses in digestive tract of juvenile common carp after chronic
exposure to sublethal tributyltin.
AB - The effect of long-term exposure to tributyltin (TBT) on the intestine-related
biochemical biomarkers in common carp was investigated in this study. Fish were
exposed at sub-lethal concentrations of TBT (75 ng/L, 0.75 and 7.5 MUg/L) for 60
days. Multiple biomarkers were measured, including digestive enzymes (trypsin,
lipase and amylase), antioxidant responses (malondialdehyde (MDA) and total
antioxidative capacity (T-AOC)), RNA/DNA ratio and the expression of digestive
related genes (try, lipc and amy). TBT exposure at 0.75 and 7.5 MUg/L led to
significantly inhibited activities of all digestive enzymes. At higher
concentration of TBT, oxidative stress was apparent as reflected by the
significant higher MDA content in the fish intestine, associated with an
inhibition of T-AOC activities. After 60 days, the RNA/DNA ratio in fish
intestine was significantly lower in groups exposed to TBT at higher
concentrations (0.75 and 7.5 MUg/L). In addition, the expression levels of try,
lipc and amy in intestine of all treated fish were inhibited, even at the
environmental concentration (75 ng/L). Our results suggest that long-term
exposure to TBT could result in different responses of intestine-related
biochemical biomarkers in fish, which could be used as new potential indicators
for monitoring residual TBT present in aquatic environment.
PMID- 25129220
TI - A comprehensive insight into bacterial virulence in drinking water using 454
pyrosequencing and Illumina high-throughput sequencing.
AB - In order to comprehensively investigate bacterial virulence in drinking water,
454 pyrosequencing and Illumina high-throughput sequencing were used to detect
potential pathogenic bacteria and virulence factors (VFs) in a full-scale
drinking water treatment and distribution system. 16S rRNA gene pyrosequencing
revealed high bacterial diversity in the drinking water (441-586 operational
taxonomic units). Bacterial diversity decreased after chlorine disinfection, but
increased after pipeline distribution. alpha-Proteobacteria was the most dominant
taxonomic class. Alignment against the established pathogen database showed that
several types of putative pathogens were present in the drinking water and
Pseudomonas aeruginosa had the highest abundance (over 110/00 of total sequencing
reads). Many pathogens disappeared after chlorine disinfection, but P. aeruginosa
and Leptospira interrogans were still detected in the tap water. High-throughput
sequencing revealed prevalence of various pathogenicity islands and virulence
proteins in the drinking water, and translocases, transposons, Clp proteases and
flagellar motor switch proteins were the predominant VFs. Both diversity and
abundance of the detectable VFs increased after the chlorination, and decreased
after the pipeline distribution. This study indicates that joint use of 454
pyrosequencing and Illumina sequencing can comprehensively characterize
environmental pathogenesis, and several types of putative pathogens and various
VFs are prevalent in drinking water.
PMID- 25129221
TI - Brewers' rice induces apoptosis in azoxymethane-induced colon carcinogenesis in
rats via suppression of cell proliferation and the Wnt signaling pathway.
AB - BACKGROUND: Brewers' rice is locally known as temukut, is a byproduct of the rice
milling process, and consists of broken rice, rice bran, and rice germ. Unlike
rice bran, the health benefit of brewers' rice has yet to be fully studied. Our
present study aimed to identify the chemopreventive potential of brewers' rice
with colonic tumor formation and to examine further the mechanistic action of
brewers' rice during colon carcinogenesis. METHODS: Male Sprague-Dawley rats were
randomly divided into five groups: (G1) normal; (G2) azoxymethane (AOM) alone;
and (G3), (G4), and (G5), which were AOM fed with 10%, 20%, and 40% (w/w) of
brewers' rice, respectively. Rats in group 2 to 5 were injected intraperitoneally
with AOM (15 mg/kg body weight) once weekly for two weeks. Colon tumor incidence
and multiplicity was assessed by hematoxylin and eosin (H&E) staining. The
expression of beta-catenin, cyclooxygenase-2 (COX-2), and Ki-67 was evaluated by
immunohistochemical staining. The apoptosis-inducing activity was analyzed using
a TUNEL assay. The data were analyzed using a one-way analysis of variance
(ANOVA) with P-value<0.05 was considered significant. RESULTS: Overall analyses
revealed that brewers' rice reduced colon tumor incidence and multiplicity. The
results from immunohistochemistry analysis also showed that brewers' rice
decreased the expression of beta-catenin, COX-2, and Ki-67 in a dose-dependent
manner. Furthermore, TUNEL analysis demonstrated that administration of brewers'
rice in AOM-induced rat colorectal cancer resulted in a dose-dependent increase
in cell apoptosis. CONCLUSIONS: Taken together, our data suggested that brewers'
rice can inhibit cell proliferation, induce apoptosis, and suppress COX-2 and
beta-catenin expression via the Wnt signaling pathway and holds great promise in
the field of chemoprevention as a dietary agent.
PMID- 25129222
TI - Quiet standing after carbohydrate ingestion induces sympathoexcitatory and
pressor responses in young healthy males.
AB - OBJECTIVE: To investigate the role of the sympathetic nervous system in the
cardiovascular response to quiet standing in the postprandial state. METHOD:
Following a 30min pre-ingestion phase, 14 healthy young male subjects consumed a
600kcal carbohydrate-rich meal. Arterial blood pressure (BP) and heart rate (HR)
were recorded for a further 120min. Measurements were obtained (Finometer) in
both the supine (5min) and standing (5min) condition every 30min. Power spectral
analysis of RR-interval and BP variability was calculated, and heart rate
responses to the baroreceptor reflex were calculated to estimate spontaneous
baroreflex sensitivity (sBRS). Derived stroke volume (SV) was measured to track
changes to postural stress postprandially. RESULTS: Quiet standing increased RR
interval low frequency power, ratio of RR-interval low frequency power/high
frequency power (ratio of RR LF/HF), and systolic BP low frequency power (SBP LF
power), and decreased RR HF power and sBRS before, and after eating. After meal
ingestion, SBP LF power increased and sBRS decreased in lying and standing
conditions. During quiet standing postprandially, DBP and the mean arterial
pressure increased (P<0.01). The increased BP is associated with increased SV
(P<0.05) early postprandially, and increased SBP LF power (P<0.01) in the later
postprandial phase. SBP LF power is inversely correlated with SV postprandially
(P<0.001, R(2)=0.96). CONCLUSION: The findings suggest a sympathetic activation
mediated by baroreflex resetting. Quiet standing in the postprandial state
enhances sympathetic outflow to the vasculature, increasing BP. SV may be a
compensatory factor stabilising BP during quiet standing early postprandially.
PMID- 25129223
TI - Hepatitis B prevalence in a multi-ethnic community in South England: a 3 year
retrospective study.
PMID- 25129224
TI - Safety of street foods in Agartala, North East India.
PMID- 25129225
TI - Assessing the relationship between medical residents' perceived barriers to SBIRT
implementation and their documentation of SBIRT in clinical practice.
PMID- 25129226
TI - Factors affecting preparedness and capacity to manage pandemic influenza:
perceptions of healthcare managers.
AB - OBJECTIVES: Numerous interventions seeking to increase preparedness for pandemic
influenza have been implemented, but low compliance of healthcare providers has
been reported in many instances. The aim of this study was to identify factors
that affect preparedness for pandemic influenza by examining: hospital managers'
perceptions of measures implemented to promote preparedness for pandemic
influenza; hospital managers' assessments of the readiness and capability of
their hospitals to manage pandemic influenza; and the effectiveness of a national
pandemic preparedness programme in Israel over time. STUDY DESIGN: A quasi
experiment was conducted following implementation of a national pandemic
preparedness programme in Israel. A survey assessed hospital managers'
perceptions of the effectiveness of the programme, and the preparedness and
capacity of their hospitals to manage pandemic influenza. Two independent
evaluations of preparedness for biological threats were conducted, based on a
validated tool that included 60 objective parameters. METHODS: Correlations
between perceived preparedness and capacity and components of the preparedness
programme were analysed using Statistical Package for the Social Sciences Version
17. Stepwise logistic regression was used to determine the components that
influence preparedness and capability to manage pandemic influenza. RESULTS: All
general hospital managers in Israel were approached twice (first and second
evaluations). Ninety-one percent rated themselves as highly/very highly prepared
for pandemic influenza, and 87% rated themselves as highly/very highly capable of
dealing with pandemic influenza. Strong correlation was found between hospital
managers' perceived preparedness and capacity to manage pandemic influenza (rho =
0.761, P = 0.000), and between perceived preparedness and familiarity with the
disease (rho = 0.605, P = 0.003). Familiarity with guidelines accounted for 35%
of the variance in perceived capability (adjusted R(2) = 0.346, P = 0.002).
Inclusion of preparedness evaluations explained an additional 15% of the variance
(R(2) change = 0.146, P = 0.026). An increase in mean total score for emergency
preparedness was found in the second evaluation compared with the first
evaluation. CONCLUSIONS: Familiarity with guidelines and preparedness evaluations
affect the perceptions of healthcare managers regarding preparedness and
capability to manage pandemic influenza.
PMID- 25129227
TI - Socio-economic correlates of functional health literacy among patients of primary
health care in Kosovo.
AB - OBJECTIVES: Functional health literacy (FHL) has been related to individual
characteristics, ill-health and disease knowledge. However, the information about
FHL in Kosovo is very limited and thus the aim of this study was to assess the
demographic and socio-economic correlates of FHL among users of primary health
care in Kosovo, a postconflict country in the Western Balkans. STUDY DESIGN:
Cross-sectional study. METHODS: A cross-sectional study was conducted in Kosovo
between November 2012-February 2013, including a representative sample of 1035
consecutive primary care users aged >=18 years (60% females; overall mean age:
44.3 +/- 16.9 years; overall response rate: 86%). Test of Functional Health
Literacy in Adults (TOFHLA) was used to assess FHL. General linear model and
logistic regression were used to assess the association of TOFHLA score with
demographic and socio-economic characteristics. RESULTS: Overall, four out of
five participants exhibited inadequate or marginal FHL in this Kosovo sample. FHL
score was independently and inversely related to age, but positively associated
with educational attainment and being in a situation other than unemployed.
CONCLUSIONS: Limited or marginal FHL was very common among primary care users in
Kosovo and considerably higher than in the neighbouring Serbia. The low health
literacy levels in Kosovo may provide an additional barrier towards achievement
of health care goals. There is a need to design and implement suitable and
effective educational and health system interventions in the Kosovo context.
PMID- 25129228
TI - Amplitude-integrated EEG revealed nonconvulsive status epilepticus in children
with non-accidental head injury.
AB - OBJECTIVE: We describe the clinical course and amplitude-integrated EEG findings
in three children with non-accidental head injury and discuss on the importance
of continuous aEEG monitoring in infants. METHODS: NCSE was defined as a
continuous 30-min seizure or briefer seizures occurring consecutively comprising
at least 30 min of any 1-h period. Non-accidental head injury was diagnosed on
the basis of neuroimaging findings such as subdural hemorrhage. Antiepileptic
treatment was performed with continuous amplitude-integrated EEG monitoring.
RESULTS: The age of the patients ranged from 48 days to nine months. All of them
had loss of consciousness and seizures on presentation. Nonconvulsive status
epilepticus without clinical symptoms were recognized in all patients. Vigorous
antiepileptic treatment against nonconvulsive status epilepticus was made in two
patients, whereas nonconvulsive status epilepticus disappeared within one hour
without additional treatment in one. CONCLUSIONS: Our experience indicates that
nonconvulsive status epilepticus were not uncommon in children with non
accidental head injury. Continuous amplitude-integrated EEG monitoring will be
one of the useful methods in encephalopathic children in order to estimate
seizure burden objectively and to treat seizures appropriately.
PMID- 25129229
TI - Dietary effect on immunological energetics in mice.
AB - Defense against natural aggressors, such as bacterial infections, requires both
energy and an immune-cellular response. However, the question as to how these two
components are interconnected in small endotherms by means of the host diet
remains only poorly understood. Here, we tested in laboratory mice whether
dietary proteins and carbohydrates can modulate the interplay between energy
expenditure, food intake and the innate and adaptive immune response when
confronting a bacterial challenge (Bacillus Calmette-Guerin, BCG). We observed
that mice fed with a high protein diet (HP) developed a better immune response
associated to increased numbers of circulating monocytes. In addition, HP diet
directly influenced the peripheral blood proportions of both T and B lymphocytes
even before the BCG challenge. Interestingly, animals that developed this type of
immune response after BCG challenge showed an increased rate of metabolism and
food consumption before being challenged. Thus, HP diet induced in non-challenged
animals a similar energy expenditure and food intake described by BCG-treated
mice. These data suggest that a high amount of proteins in diet can modify the
energetic and nutrient dynamic in the host causing a better immune reaction
against a microbial challenge.
PMID- 25129230
TI - Modeling of rhythmic behavior in neutral lipid production due to continuous
supply of limited nitrogen: mutual growth and lipid accumulation in microalgae.
AB - The relative effects of three precise nitrogen limitation regimes on green micro
algae were assessed using the Trebouxiophycean alga Coccomyxa subellipsoidea
grown in a chemostatic bioreactor system. The data provides further evidence that
growth and triglyceride (TAG) accumulation are concurrent and independently
proportional to the degree of nitrogen limitation in algae. Additionally, TAG
accumulation was observed to proceed via oscillations with respect to time and
percent dry weight quantity. The predator-prey model was applied to fit the
experimental data and to obtain the physiological significance of these
oscillations. The results determine the conditions of maximum neutral lipid
productivity with respect to nitrate stress and highlight an area of potential
future research.
PMID- 25129231
TI - Effects of solubility properties of solvents and biomass on biomass pretreatment.
AB - Hildebrand solubility parameters of biomasses and pretreatment solvents were
examined by a method of intrinsic viscosity. This is to be used as basic
information in selecting a suitable solvent for biomass pretreatment processes.
The effects of mixing1-ethyl-3-methylimidazolium acetate (EMIM-AC) and different
solvents, lignin content in a pretreatment solvent, and biomass type on the
Hildebrand solubility parameter and thermodynamic properties were carried out and
calculated in this work. The Hildebrand solubility parameters of the mixtures are
according to those of organic solvents: deltaH[EMIM-AC/DMA]=25.071,000,000Da) at 50% of the cell dry weight (<8h).
P3HB also resulted from incubation with acetate, crotonate, or a mixture of
hydrolytic depolymerization products. Poly(3-hydroxybutyric acid-co-3
hydroxyvaleric acid) (PHBV) resulted from incubation with valerate or 2
pentenoate. A recycling strategy where abiotic depolymerization of waste PHAs
yields feedstock for customized PHA re-synthesis appears feasible, without the
need for energy-intensive feedstock purification.
PMID- 25129233
TI - The effect of poly-beta-hydroxyalkanoates degradation rate on nitrous oxide
production in a denitrifying phosphorus removal system.
AB - Poly-beta-hydroxyalkanoates (PHAs) and free nitrous acid (FNA) have been revealed
as significant factors causing nitrous oxide (N2O) production in denitrifying
phosphorus removal systems. In this study, the effect of PHA degradation rate on
N2O production was studied at low FNA levels. N2O production always maintained at
approximately 40% of the amount of nitrite reduced independent of the PHA
degradation rate. The electrons distributed to nitrite reduction were 1.6 times
that to N2O reduction. This indicated that electron competition between these two
steps was not affected by the PHA degradation rate. Continuous feed of nitrate
was proposed, and demonstrated to reduce N2O accumulation by 75%. While being
kept low, a possible compounding effect of a low-level FNA could not be ruled
out. The sludge used likely contained both polyphosphate- and glycogen
accumulating organisms, and the results could not be simply attributed to either
group of organisms.
PMID- 25129234
TI - Diversity and dynamics of the microbial community on decomposing wheat straw
during mushroom compost production.
AB - The development of communities of three important composting players including
actinobacteria, fungi and clostridia was explored during the composting of wheat
straw for mushroom production. The results revealed the presence of highly
diversified actinobacteria and fungal communities during the composting process.
The diversity of the fungal community, however, sharply decreased in the mature
compost. Furthermore, an apparent succession of both actinobacteria and fungi
with intensive changes in the composition of communities was demonstrated during
composting. Notably, cellulolytic actinomycetal and fungal genera represented by
Thermopolyspora, Microbispora and Humicola were highly enriched in the mature
compost. Analysis of the key cellulolytic genes revealed their prevalence at
different composting stages including several novel glycoside hydrolase family 48
exocellulase lineages. The community of cellulolytic microbiota also changed
substantially over time. The prevalence of the diversified cellulolytic
microorganisms holds the great potential of mining novel lignocellulose
decomposing enzymes from this specific ecosystem.
PMID- 25129236
TI - Absolute and relative quantification of RNA modifications via biosynthetic
isotopomers.
AB - In the resurging field of RNA modifications, quantification is a bottleneck
blocking many exciting avenues. With currently over 150 known nucleoside
alterations, detection and quantification methods must encompass multiple
modifications for a comprehensive profile. LC-MS/MS approaches offer a
perspective for comprehensive parallel quantification of all the various
modifications found in total RNA of a given organism. By feeding (13)C-glucose as
sole carbon source, we have generated a stable isotope-labeled internal standard
(SIL-IS) for bacterial RNA, which facilitates relative comparison of all
modifications. While conventional SIL-IS approaches require the chemical
synthesis of single modifications in weighable quantities, this SIL-IS consists
of a nucleoside mixture covering all detectable RNA modifications of Escherichia
coli, yet in small and initially unknown quantities. For absolute in addition to
relative quantification, those quantities were determined by a combination of
external calibration and sample spiking of the biosynthetic SIL-IS. For each
nucleoside, we thus obtained a very robust relative response factor, which
permits direct conversion of the MS signal to absolute amounts of substance. The
application of the validated SIL-IS allowed highly precise quantification with
standard deviations<2% during a 12-week period, and a linear dynamic range that
was extended by two orders of magnitude.
PMID- 25129237
TI - Generalization from episodic memories across time: a route for semantic knowledge
acquisition.
AB - The storage of input regularities, at all levels of processing complexity, is a
fundamental property of the nervous system. At high levels of complexity, this
may involve the extraction of associative regularities between higher order
entities such as objects, concepts and environments across events that are
separated in space and time. We propose that such a mechanism provides an
important route towards the formation of higher order semantic knowledge. The
present study assessed whether subjects were able to extract complex regularities
from multiple associative memories and whether they could generalize this
regularity knowledge to new items. We used a memory task in which subjects were
required to learn face-location associations, but in which certain facial
features were predictive of locations. We assessed generalization, as well as
memory for arbitrary stimulus components, over a 4-h post-encoding consolidation
period containing wakefulness or sleep. We also assessed the stability of
regularity knowledge across a period of several weeks thereafter. We found that
subjects were able to detect the regularity structure and use it in a
generalization task. Interestingly, the performance on this task increased across
the 4hr post-learning period. However, no differential effects of cerebral sleep
and wake states during this interval were observed. Furthermore, it was found
that regularity extraction hampered the storage of arbitrary facial features,
resulting in an impoverished memory trace. Finally, across a period of several
weeks, memory for the regularity structure appeared very robust whereas memory
for arbitrary associations showed steep forgetting. The current findings improve
our understanding of how regularities across memories impact memory
(trans)formation.
PMID- 25129235
TI - Fetal exposure to maternal depressive symptoms is associated with cortical
thickness in late childhood.
AB - BACKGROUND: Maternal depression is one of the most common prenatal complications.
The consequences of fetal exposure to maternal depression are poorly understood.
The aim of this study is to examine the association between fetal exposure to
maternal depressive symptoms and cortical thickness in children 6-9 years old.
METHODS: A prospective, longitudinal study of maternal depressive symptoms at 19,
25, and 31 weeks' gestation was followed by acquisition of a structural magnetic
resonance imaging scan in 81 children (age, 86.1 +/- 9.9 months). RESULTS:
Significant (p < .01) cortical thinning in children primarily in the right
frontal lobes was associated with exposure to prenatal maternal depression. The
strongest association was at 25 weeks' gestation; exposure to maternal depression
at 25 gestational weeks was associated with cortical thinning in 19% of the whole
cortex and 24% of the frontal lobes, primarily in the right superior, medial
orbital, and frontal pole regions of the prefrontal cortex (p < .01). The
significant association between prenatal maternal depression and child
externalizing behavior (p < .05) was mediated by cortical thinning in prefrontal
areas of the right hemisphere. CONCLUSIONS: The pattern of cortical thinning in
children exposed to prenatal maternal depression is similar to patterns in
depressed patients and in individuals with risk for depression. Exposure to
prenatal depression coupled with subsequent cortical thinning was associated with
presence of externalizing behavior in preadolescent children and may be prodromal
markers of risk for dysphoria. Vulnerability to prenatal influences at 25
gestational weeks may result from the enormous growth and dramatic structural
changes in the nervous system.
PMID- 25129238
TI - Hypoxic signature of microRNAs in glioblastoma: insights from small RNA deep
sequencing.
AB - BACKGROUND: Hypoxia is a critical aspect of the glioma microenvironment and has
been associated with poor prognosis and resistance to various therapies. However,
the mechanisms responsible for hypoxic survival of glioma cells remain unclear.
Recent studies strongly suggest that microRNAs act as critical mediators of the
hypoxic response. We thus hypothesized their prominent role in hypoxia resistance
in glioblastoma (GBM) and aimed to identify those. RESULTS: With this study, we
present the first detailed analysis of small RNA transcriptome of cell line
U87MG, a grade IV glioma cell line, and its alteration under hypoxic condition.
Based on deep sequencing and microarray data, we identify a set of hypoxia
regulated microRNAs, with the miR-210-3p and its isomiRs showing highest
induction in GBM cell lines U87MG and U251MG. We show miR-210-3p, miR-1275, miR
376c-3p, miR-23b-3p, miR-193a-3p and miR-145-5p to be up-regulated, while miR-92b
3p, miR-20a-5p, miR-10b-5p, miR-181a-2-3p and miR-185-5p are down-regulated by
hypoxia. Interestingly, certain hypoxia-induced miRNAs are also known to be over
expressed in GBM tumors, suggesting that hypoxia may be one of the factors
involved in establishing the miRNA signature of GBM. Transcription factor binding
sites for Hypoxia inducible factor 1 A (HIF1A) were identified in the promoter
region (5 kb upstream) of 30 hypoxia-induced miRNAs. HIF-1A over-expression and
silencing studies show regulation of specific miRNAs, including miR-210-3p, to be
HIF1A dependent. On the other hand, miR-210-3p leads to an increase in
transcriptional activity of HIF and its target genes vascular endothelial growth
factor (VEGF) and carbonic anhydrase 9 (CA9). MiR-210-3p levels were found to be
high in GBM patient samples and showed good correlation with the known hypoxia
markers CA9 and VEGF. We show that miR-210-3p promotes hypoxic survival and
chemoresistance in GBM cells and targets a negative regulator of hypoxic
response, HIF3A. Additionally, a total of 139 novel miRNAs were discovered by the
analysis of deep sequencing data and three of these were found to be
differentially expressed under hypoxia. CONCLUSIONS: Overall, our study reveals a
novel miRNA signature of hypoxia in GBM and suggests miR-210-3p to be an
oncogenic player and a novel potential intrinsic marker of hypoxia in
glioblastoma.
PMID- 25129239
TI - Quantitative electroencephalogram utility in predicting conversion of mild
cognitive impairment to dementia with Lewy bodies.
AB - Mild cognitive impairment (MCI) as a precursor of dementia with Lewy bodies (DLB)
is the focus of recent research, trying to explore the early mechanisms and
possible biomarkers of DLB. Quantitative electroencephalogram (QEEG) methods are
able to differentiate early DLB from Alzheimer's disease (AD). The aim of the
present study was to assess whether QEEG abnormalities, characterized by dominant
frequency <8 Hz and dominant frequency variability >1.5 Hz, typical of early DLB,
are already present at the stage of MCI and to evaluate whether EEG abnormalities
can predict the development of DLB. Forty-seven MCI subjects were followed for 3
years. EEG recordings were obtained at admission and at the end of the study. At
the end of follow-up, 20 subjects had developed probable DLB (MCI-DLB), 14 had
probable AD (MCI-AD), 8 did not convert to dementia, 5 developed a non-AD/DLB
dementia. One hundred percent of MCI-DLB showed EEG abnormalities at admission.
Ninety three percent of MCI-AD maintained a normal EEG throughout the study. QEEG
may represent a powerful tool to predict the progression from MCI to DLB with a
sensitivity and specificity close to 100%.
PMID- 25129240
TI - SNCA variants rs2736990 and rs356220 as risk factors for Parkinson's disease but
not for amyotrophic lateral sclerosis and multiple system atrophy in a Chinese
population.
AB - Previous studies found that polymorphisms rs2736990 and rs356220 in the alpha
synuclein (SNCA) gene increase the risk for Parkinson's disease (PD) in a
Caucasian population. In consideration of the overlapping of clinical
manifestations and pathologic characteristics among PD, amyotrophic lateral
sclerosis (ALS), and multiple system atrophy (MSA), the possible associations of
these 2 polymorphisms and 3 neurodegenerative diseases were studied in the
Chinese population. A total of 1011 PD, 778 sporadic ALS (SALS), 264 MSA
patients, and 721 healthy controls (HCs) were studied. All subjects were
genotyped for the 2 polymorphisms using polymerase chain reaction and direct
sequencing. Significant differences in the genotype frequencies (p = 0.0188 and
0.0064, respectively) and minor allele frequencies (MAFs) (p = 0.0065 and 0.0095,
respectively) of rs2736990 and rs356220 were observed between the PD patients and
HCs. Moreover, significant differences were found between the early-onset PD
patients (<50 years) and matched controls but not in the late-onset PD patients
(>=50 years). However, no differences were observed between subgroups with regard
to clinical features, such as sex, onset symptoms (tremor or rigidity), cognition
(normal or abnormal), and anxiety and depression (presence or absence). No
significant differences were found in the genotype frequencies and MAFs of these
2 single-nucleotide polymorphisms between SALS patients and HCs and between MSA
patients and HCs. No significant differences were found between subgroups with
regard to the clinical presentation of SALS and MSA. Our results show that
rs2736990 and rs356220 in SNCA decreased the risk for PD in a Chinese population.
These candidate polymorphisms were unlikely to be the causes of SALS and MSA in
this population.
PMID- 25129241
TI - Predictable dental rehabilitation in maxillomandibular reconstruction with free
flaps. The role of implant guided surgery.
AB - The reconstruction of maxillomandibular defects secondary to oral cancer surgery,
represent a great challenge for Maxillofacial surgeons. During the last decades
the reconstructive surgery has experimented a big advance due to the development
of the microsurgical techniques. At present, we are able to reconstruct complex
defects using free flaps that provide both soft and bone tissue. Fibula, iliac
crest and scapula free flaps have been the three classic options for the
maxillomandibular reconstruction owing to the amount of bone that this flaps
provide, allowing the posterior dental rehabilitation with implants. Today, our
objective it is not only the aesthetic reconstruction, but also the functional
reconstruction of the patients enhancing their life quality. Guided implant
surgery in free flap reconstructed patients has become an essential tool, helping
to define the exact position of the dental implant in the flap. In this way it is
possible to look for the areas with better bone conditions, avoiding the
osteosynthesis material used to fixate the flap with the native bone and deciding
the best biomechanical option, in terms of number and situation of the implants,
for the future dental prostheses. In summary, using the guided implant surgery,
it is possible to design an exact and predictable dental implant rehabilitation
in patients with oral cancer who are reconstructed with free microvascular flap,
resulting in an optimal aesthetic and functional result.
PMID- 25129242
TI - Morphological and topographical characteristics of posterior supernumerary molar
teeth: an epidemiological study on 25,186 subjects.
AB - OBJECTIVES: To investigate the prevalence , gender difference , arch , morphology
and position within the arch of supernumerary molar (SM) teeth in a referred
Italian Caucasian population. STUDY DESIGN: Records of 25,186 young patients were
evaluated. Only data related to supernumerary teeth in the posterior region of
the jaws were analyzed. The diagnosis of hyperdontia was formulated during the
clinical and radiological examinations based on panoramic radiographs.
Statistical analysis was conducted at level of subjects in the assessment of
prevalence of SMs and sex ratio. Statistical analysis was conducted at level of
teeth according to their morphological and topographic characteristics. The
analysis of association between supernumerary morphology and arch, between
supernumerary position and arch and between morphology and position was performed
using the chi2 test (P<= 0.05). RESULTS: 61 posterior supernumerary teeth were
found in 45 patients. The male to female ratio was 2.5:1 ;the mean age was 21.23
(IC:95%).The SMs were found more frequently in the maxilla (62.3%) than in the
mandible; supernumerary teeth (60.7%) were more frequent than supplemental teeth.
The SMs were mostly of tuberculate shape (56.8%) and paramolars teeth (64.9%)
were more common than distomolars. 54% of teeth were erupted in the arch. No
statistically significant relationship were found between the supernumerary teeth
shape and the arch (P= 0.087) , between supernumerary teeth position and the arch
(P=0.511) and between morphology and position (P=0.216). CONCLUSIONS:
Epidemiological studies related to supernumerary teeth can be useful to
clinicians in the early diagnosis of this anomaly. In this retrospective study
the prevalence of SMs was 0.18%. SMs were more frequent in males and in the
maxilla. Supernumerary were more frequent than supplemental; the conical
morphology and paramolar position were the most common shape and position.
PMID- 25129243
TI - Significant association of MTHFD1 1958G>A single nucleotide polymorphism with
nonsyndromic cleft lip and palate in Indian population.
AB - OBJECTIVE: Nonsyndromic cleft lip and palate (NSCLP) is genetically distinct from
those with syndromic clefts, and accounts for ~70% of cases with Oral clefts.
Folate, or vitamin B9, is an essential nutrient in our diet. Allelic variants in
genes involved in the folate pathway might be expected to have an impact on risk
of oral clefts. Given the key role of methylenetetrahydrofolate dehydrogenase 1
(MTHFD1) in folate metabolism, it would be of significant interest to assess its
role in NSCLP etiology. STUDY DESIGN: The present study aims at examining the
association between MTHFD1 1958G>A polymorphism and NSCLP risk by conducting a
case-control study in south Indian population. Our sample comprised of 142 cases
with nonsyndromic clefts and 141 controls without clefts or family history of
clefting. The MTHFD1 1958G>A polymorphism was genotyped using PCR-RFLP. RESULTS:
An increased risk was found for the heterozygous 1958GA (OR=2.44; P=0.020) and
homozygous 1958AA (OR=2.45; P=0.012) genotypes in the children. When the dominant
model (AG+AA vs GG) was applied the risk remained the same as co-dominant model,
but the level of significance increased (OR=2.44; P=0.002). CONCLUSION: The
results indicated the MTHFD1 1958G>A polymorphism to be one of the important
genetic determinants of NSCLP risk in South Indian subjects.
PMID- 25129244
TI - Ameloblastomas: clinicopathological features from 70 cases diagnosed in a single
oral pathology service in an 8-year period.
AB - Ameloblastomas are odontogenic tumors that can present some distinct
clinicopathological profiles when comparing different populations and studies.
OBJECTIVES: The aim of the present study was to analyze the clinicopathological
features from a series of ameloblastomas diagnosed in a single Oral Pathology
service in Brazil in an 8-year period. STUDY DESIGN: The files were revised and
all cases diagnosed as ameloblastomas in the period were retrieved. All
hematoxylin and eosin stained histological slides were reviewed and all clinical
and radiological information were obtained through a review of the laboratory
forms. Data were descriptively analyzed and a comparison was performed with the
different ameloblastomas subtypes. RESULTS: Seventy ameloblastomas composed the
final sample, including 57 (81%) solid/multicystic, 9 (13%) unicystic, 2 (3%)
desmoplastic and 2 (3%) peripheral ameloblastomas. Mean age of the affected
patients was in the forth decade of life and there was a slight male
predominance. Most tumors presented as multilocular radiolucencies, were located
in the posterior mandible and showed the follicular and plexiform histological
patterns. There was no difference on the mean age of the patients affected by
solid and unicystic ameloblastomas. CONCLUSIONS: The present results showed that
the clinicopathological features of the ameloblastomas included in this Brazilian
sample were similar to the features described in most other worldwide
populations.
PMID- 25129245
TI - Analysis of methylation and mRNA expression status of FADD and FAS genes in
patients with oral squamous cell carcinoma.
AB - BACKGROUND: Apoptosis is an important mechanism that is responsible for the
physiological deletion of harmful, damaged, or unwanted cells. Changed expression
of apoptosis-related genes may lead to abnormal cell proliferation and finally to
tumor genesis. Our aims were to analyze the promoter methylation and gene
expression profiles of FADD and FAS genes in risk of OSCC. MATERIAL AND METHODS:
we analyze the promoter methylation status of FADD and FAS genes using
Methylation - Specific PCR (MSP) in 86 OSCC tissues were kept in paraffin and 68
normal oral tissues applied as control. Also, FADD and FAS genes expression were
analyzed in 19 cases and 20 normal specimens by Real-Time Reverse-Transcripts
PCR. RESULTS: Aberrant promoter methylation of FADD and FAS genes were detected
in 12.79 % (11 of 86) and 60.46 % (52 of 86) of the OSCC cases, respectively,
with a significant difference between cases and healthy controls for both FADD
and FAS genes (P < 0.001). The gene expression analysis showed statistically
significant difference between cases and healthy controls for both FADD (p<0.02)
and FAS (p<0.007) genes. CONCLUSIONS: To the best our knowledge, the data of this
study are the first report regarding, the effect of promoter hypermethylation of
the FADD and FAS genes in development of OSCC. To confirm the data, it is
recommended doing further study in large sample sizes in various genetic
populations.
PMID- 25129246
TI - Association of -1082 interleukin-10 gene polymorphism in Peruvian adults with
chronic periodontitis.
AB - OBJECTIVES: The aim of this study was to assess association of the -1082 IL-10
gene polymorphism with chronic periodontitis CP in a Peruvian population. STUDY
DESIGN: Samples of venous blood and DNA were obtained from 106 Peruvian subjects:
a) 53 periodontally healthy; and b) 53 with CP. The association of the -1082 IL
10 promoter sequences was assessed by Polymerase chain reaction-restriction
fragment length polymorphism (PCR-RFLP). Student's t test were used to assess the
clinical parameters, as well as the chi2 test and the odds ratio (OR), with 95%
confidence intervals (CI) used performed for estimates regarding genotype and
allele frequencies. RESULTS: There were statistically significant differences
between groups regarding the mean bleeding on probing, mean attachment level and
mean probing depth (p < 0.00001) indicating that the matching based on the
evaluated groups was adequate. The chi2 test found a statistically significant
imbalance of genotypes between groups (p = 0.0172). The prevalence of CP was
significantly higher in subjects harboring at least one A allele at position
1082 (AA and GA genotypes) in comparison to patients with the GG genotype (OR =
2.96; CI: 0.52; 5.41; p = 0.0099). Equally, subjects with the AA genotype were
significantly associated to a diagnosis of CP (OR = 2.71; CI: 0.38; 5.04; p =
0.0231). On the other hand, subjects presenting a healthy periodontal status
presented at least one G allele in comparison with the AA genotype (OR = 0.37;
CI: 0.05, 0.69; p = 0.0231). For subjects with the GG genotype, the same positive
association was observed (OR = 0.34; CI: 0.06, 0.62; p = 0.0099). There were no
significant differences between groups amongst subjects with the GA genotype (OR
= 1.19; CI: 0.22, 2.16; p = 0.6774). CONCLUSIONS: Within the limits of this
study, IL-10 gene polymorphism at position -1082 does not appear to be associated
to CP. Conversely, subjects with AA genotype seem to be at an increased risk of
developing CP.
PMID- 25129247
TI - Effect of low-dose dexketoprofen trometamol and paracetamol on postoperative
complications after impacted third molar surgery on healthy volunteers: A pilot
study.
AB - OBJECTIVES: The aim of the present study was to investigate the analgesic and
anti-inflammatory effects of dexketoprofen trometamol (DT) and paracetamol on
deep acute somatic pain and inflammation in patients undergoing impacted third
molar surgery. This study was planned to present benefits that we could obtain
with low burden of drug. STUDY DESIGN: Effects of drugs, which were administered
preemptively before the procedure, on pain, mouth-opening limitation, and
swelling were assessed by visual analogue scale (VAS), magnetic resonance imaging
(MRI), and mouth-opening measurement. Following surgery, time intervals when the
patients first need to receive the drug were measured. RESULTS: The VAS scores of
the patients were lower in the side treated with DT than that in the paracetamol
treated side. There was no significant difference between the groups in terms of
mouth-opening limitation. MRI recordings revealed that swelling was lower in the
side treated with paracetamol than DT treated side. CONCLUSIONS: Administration
of the drugs before surgery contributed to the postoperative patient comfort. The
analgesic activity of 12.5 mg dose of DT was similar to, even better than, the
analgesic activity of 500 mg dose of paracetamol; however, DT had insufficient
anti-inflammatory efficacy.
PMID- 25129248
TI - The clinical significance of CDK1 expression in oral squamous cell carcinoma.
AB - OBJECTIVES: To evaluate the clinical significance of cyclin-dependent kinase 1
(CDK1) in 77 oral squamous cell carcinomas (OSCC) using immunohistochemical
methods. STUDY DESIGN: Immunohistochemical expression of CDK1 was compared with
various clinicopathological features in 77 OSCC and 60 controlled epithelia
adjacent to the tumours. In addition, correlation of CDK1 expression and
prognostic and the 5-year accumulative survival rate of OSCC were investigated.
RESULTS: The CDK1 protein was expressed in 52 cases of 77 tumor tissues (67.5%),
compared with 21 cases of 60 controlled (35.0%). The expression of CDK1 was
significantly correlated with the histological grade of OSCC (P<0.05). The CDK1
protein was over-expressed in recurrent tumors or in those with lymph node
metastasis. Statistical analysis showed a significant reduction in the 5-year
accumulative survival rate in CDK1 positive cases compared with CDK1 negative
cases (P<0.05). Namely, the CDK1 positive patients had poor prognosis.
CONCLUSIONS: The expression of CDK1 might serve as malignant degree and
prognostic markers for the survival of OSCC.
PMID- 25129249
TI - Odontogenic myxofibroma: a concise review of the literature with emphasis on the
surgical approach.
AB - PURPOSE: The aim of this work is to report a review of the literature concerning
epidemiology, clinical and radiographic features as well as treatment of
odontogenic myxofibroma (MF). METHODS: The PubMed database was searched using the
following keywords: "odontogenic myxofibroma", "odontogenic fibromyxoma",
"myxofibroma of the jaw" and "fibromyxoma of the jaw". RESULTS: Fifteen articles
reporting the experience with 24 patients were identified. Male/female ratio was
1:1.4 and the average age 29.5 years. The most frequent location was the
mandible. In 66.7% of the cases the radiographic appearance was a multilocular
radiolucency. Swelling was observed in 13 patients (92.86%), varying degrees of
pain in 5 (35.71%) and paresthesia in only one patient (7.14%). Six out of 24
patients (26.09%) were treated with radical surgery and 17 out of 24 (73.91%)
with a conservative approach. In two out of 21 cases (9.52%) a recurrence was
reported. CONCLUSIONS: MF is an extremely rare tumour and no agreement exist on
the causes of its development. According to the present review, the choice of
treatment should depend on variables such as localization, presence of a primary
or of a recurrent lesion, age, general medical conditions and aesthetic needs of
the patient.
PMID- 25129250
TI - Transition from glass to digital slide microscopy in the teaching of oral
pathology in a Brazilian dental school.
AB - OBJECTIVES: Several medical and dental schools have described their experience in
the transition from conventional to digital microscopy in the teaching of general
pathology and histology disciplines; however, this transitional process has
scarcely been reported in the teaching of oral pathology. Therefore, the
objective of the current study is to report the transition from conventional
glass slide to virtual microscopy in oral pathology teaching, a unique experience
in Latin America. STUDY DESIGN: An Aperio ScanScope(r) scanner was used to
digitalize histological slides used in practical lectures of oral pathology. The
challenges and benefits observed by the group of Professors from the Piracicaba
Dental School (Brazil) are described and a questionnaire to evaluate the
students' compliance to this new methodology was applied. RESULTS: An improvement
in the classes was described by the Professors who mainly dealt with questions
related to pathological changes instead of technical problems; also, a higher
interaction with the students was described. The simplicity of the software used
and the high quality of the virtual slides, requiring a smaller time to identify
microscopic structures, were considered important for a better teaching process.
CONCLUSIONS: Virtual microscopy used to teach oral pathology represents a useful
educational methodology, with an excellent compliance of the dental students.
PMID- 25129251
TI - Influence of bone parameters on peri-implant bone strain distribution in the
posterior mandible.
AB - OBJECTIVES: The success rate of dental implants depends on the type of bone at
the implant site. The purpose of the present study was to investigate the effects
of the bone parameters at the implant-placement site on peri-implant bone strain
distributions. STUDY DESIGN: The morphologies and bone densities of seventy-five
potential implant sites in the posterior mandible were measured using computed
tomography (CT). Based on the CT data, we defined bone parameters (low and high
in terms of cancellous-bone density and crestal-cortical bone density, and thin
and thick in terms of crestal-cortical bone thickness), and we constructed finite
element models simulating the various bone types. A buccolingual oblique load of
200 N was applied to the top of the abutment. The von Mises equivalent (EQV)
strains in the crestal-cortical bone and in the cancellous bone around the
implant were calculated. RESULTS: Cancellous-bone density greatly affected the
maximum EQV strain regardless of the density and thickness of the crestal
cortical-bone. The maximum EQV strains in the crestal cortical-bone and the
cancellous bone in the low-density cancellous-bone models (of 150 Hounsfield
units (HU)) were 1.56 to 2.62-fold and 3.49 to 5.31-fold higher than those in the
high-density cancellous-bone models (of 850 HU), respectively. The crestal
cortical-bone density affected the maximum EQV strains in the crestal cortical
bone and in the cancellous bone in the low-density cancellous-bone models. The
crestal cortical-bone thickness affected the maximum EQV strains in the
cancellous bone and in the crestal cortical-bone in the low-density cancellous
bone models. CONCLUSIONS: Our results confirm the importance of bone types for
the peri-implant bone strain distribution. Cancellous-bone density may be a
critical factor for peri-implant bone strain.
PMID- 25129252
TI - In vitro preliminary study of osteoblast response to surface roughness of
titanium discs and topical application of melatonin.
AB - OBJECTIVES: To observe human osteoblast behavior cultured in vitro on titanium
discs (Ti) in relation to surface roughness and melatonin application. STUDY
DESIGN: Human osteoblasts (MG-63) were cultured on 60 Ti6Al4V discs divided into
three groups: Group I: discs treated with dual acid etching; Group II dual acid
etching and blasting with calcium phosphate particles; Group III (control)
machined discs. Surface roughness and topography of the discs were examined with
scanning electron microscope (SEM) and confocal laser scanning electron
microscope( CLSM). Osteoblast adhesion, proliferation and cell morphology were
determined by means of fluorescence microscopy with Image-Pro Plus software and
SEM. RESULTS: Group II presented the roughest discs, while the least rough were
Group III. Cell adhesion was greatest in Group II. The addition of melatonin
improved cell proliferation. CONCLUSIONS: 1. Surface treatments (dual acid
etching, calcium phosphate impaction) increase surface roughness in comparison
with machined titanium. 2. Greater surface roughness tends to favor cell adhesion
after 24-hour cell culture. 3. The addition of melatonin tends to favor
osteoblast proliferation.
PMID- 25129253
TI - Mechanical behavior of provisional implant prosthetic abutments.
AB - INTRODUCTION: Implant-supported prostheses have to overcome a major difficulty
presented by the morphology and esthetics of peri-implant tissues in the anterior
sector. Diverse therapeutic techniques are used for managing the mucosa adjacent
to the implant and the most noteworthy is immediate/deferred fixed
provisionalization. OBJECTIVES: In vitro testing of strength and deformation of
implant prosthetic abutments made from different materials
(Titanium/PEEK/methacrylate). MATERIAL AND METHODS: Forty Sweden & Martina(r)
implant prosthetic abutments (n=40) were divided into five groups: Group MP:
methacrylate provisional abutments with machined titanium base; Group PP:
Polyether ether ketone (PEEK) provisional abutments; Group TP: titanium
provisional abutments; Group TAD: titanium anti-rotational definitive abutments;
Group TRD: titanium rotational definitive abutments. Their mechanical behavior
under static loading was analyzed. Samples were examined under a microscope to
determine the type of fracture produced. RESULTS AND CONCLUSIONS: Definitive anti
rotational titanium abutments and definitive rotational titanium abutments
achieved the best mean compression strength, while PEEK resin provisional
abutments obtained the lowest. The group that showed the greatest elastic
deformation was the group of titanium provisional abutments.
PMID- 25129254
TI - Pfeiffer syndrome: clinical and genetic findings in five Brazilian families.
AB - Pfeiffer syndrome (PS) is mainly characterized by craniosysnostosis, midface
hypoplasia, great toes with partial syndactyly of the digits, broad and medially
deviated thumbs. It is caused by allelic mutations in the fibroblast growth
factor receptor 1 and 2 (FGFR1 and 2) genes. This study describes the clinical
and genetic features of five Brazilian families affected by PS. All patients
exhibited the classical phenotypes related to PS. The genetic analysis was able
to detect the mutations Cys278Phe, Cys342Arg, and Val359Leu in three of these
families. Two mutations were de novo, with one familial. We identified pathogenic
mutations in four PS cases in five Brazilian families by PCR sequencing of FGFR1
exon 5 and FGFR2 exons 5, 8, 10, 11, 15, and 16. The clinical and genetic aspects
of these families confirm that this syndrome can be clinically variable, with
different mutations in the FGFR2 responsible for PS.
PMID- 25129255
TI - Genetic control of nerve conduction velocity may influence multiple sclerosis
phenotype.
AB - This commentary highlights the article by Lemcke et al that reports a
polymorphism in the Inpp4b gene, which is associated with increased risk of
developing multiple sclerosis.
PMID- 25129256
TI - Nerve conduction velocity is regulated by the inositol polyphosphate-4
phosphatase II gene.
AB - Impairment of nerve conduction is common in neurodegenerative and
neuroinflammatory diseases such as multiple sclerosis (MS), and measurement of
evoked potentials (visual, motor, or sensory) has been widely used for diagnosis
and recently also as a prognostic marker for MS. We used a classical genetic
approach to identify novel genes controlling nerve conduction. First, we used
quantitative trait mapping in F2 progeny of B10/SJL mice to identify EAE31, a
locus controlling latency of motor evoked potentials (MEPs) and clinical onset of
experimental autoimmune encephalomyelitis. Then, by combining congenic mapping,
in silico haplotype analyses, and comparative genomics we identified inositol
polyphosphate-4-phosphatase, type II (Inpp4b) as the quantitative trait gene for
EAE31. Sequence variants of Inpp4b (C/A, exon 13; A/C, exon 14) were identified
as differing among multiple mouse strains and correlated with individual cortical
MEP latency differences. To evaluate the functional relevance of the amino acid
exchanges at positions S474R and H548P, we generated transgenic mice carrying the
longer-latency allele (Inpp4b(474R/548P)) in the C57BL/6J background.
Inpp4b(474R/548P) mice exhibited significantly longer cortical MEP latencies (4.5
+/- 0.22 ms versus 3.7 +/- 0.13 ms; P = 1.04 * 10(-9)), indicating that INPP4B
regulates nerve conduction velocity. An association of an INPP4B polymorphism
(rs13102150) with MS was observed in German and Spanish MS cohorts (3676 controls
and 911 cases) (P = 8.8 * 10(-3)).
PMID- 25129257
TI - A novel frameshift mutation in BLM gene associated with high sister chromatid
exchanges (SCE) in heterozygous family members.
AB - The Bloom syndrome (BS) is an autosomic recessive disorder comprising a wide
range of abnormalities, including stunted growth, immunodeficiency, sun
sensitivity and increased frequency of various types of cancer. Bloom syndrome
cells display a high level of genetic instability, including a 10-fold increase
in the sister chromatid exchanges (SCE) level. Bloom syndrome arises through
mutations in both alleles of the BLM gene, which was identified as a member of
the RecQ helicase family. In this study, we screened a Tunisian family with three
BS patients. Cytogenetic analysis showed several chromosomal aberrations, and an
approximately 14-fold elevated SCE frequency in BS cells. A significant increase
in SCE frequency was observed in some family members but not reaching the BS
patients values, leading to suggest that this could be due to the heterozygous
profile. Microsatellite genotyping using four fluorescent dye-labeled
microsatellite markers revealed evidence of linkage to BLM locus and the healthy
members, sharing higher SCE frequency, showed heterozygous haplotypes as
expected. Additionally, the direct BLM gene sequencing identified a novel
homozygous frameshift mutation c.3617-3619delAA (p.K1207fsX9) in BS patients and
a heterozygous BLM mutation in the family members with higher SCE frequency. Our
findings suggest that this latter mutation likely leads to a reduced BLM activity
explaining the homologous recombination repair defect and, therefore, the
increase in SCE. Based on the present data, the screening of this mutation could
contribute to the rapid diagnosis of BS. The genetic confirmation of the mutation
in BLM gene provides crucial information for genetic counseling and prenatal
diagnosis.
PMID- 25129259
TI - Invasive fungal disease in systemic lupus erythematosus: a systematic review of
disease characteristics, risk factors, and prognosis.
AB - OBJECTIVES: Invasive fungal disease (IFD) is a life-threatening complication of
systemic lupus erythematosus (SLE) and/or its treatment. We conducted a
systematic review to characterize IFD in SLE and identify risk factors and
outcomes. METHODS: MEDLINE, Embase, and Web of Science were searched up to June
2013 using MeSH terms and keywords pertaining to SLE and IFD. Two independent
reviewers selected adult cohort studies and case series/reports on IFD in SLE
based on the established classification criteria for both diseases. RESULTS: In
total, 393 cases from 182 studies met the criteria for inclusion. Cryptococcus
spp., Aspergillus spp., and Candida spp. were the most common fungal pathogens.
Cohorts described IFD in 0.6-3.2% of SLE inpatients and 0.28% of SLE outpatients.
IFD occurred at a median of 2 years of disease duration (IQR: 0.5-7.1), and 39%
of cases occurred within the first year of SLE. Disease activity and
corticosteroid dose >60mg/day emerged as risk factors for IFD. IFD was associated
with a mortality rate of 53% (161/316 cases), and worse in the absence of
antifungal therapy (n = 43). Overall, 44 cases of IFD were only diagnosed on
autopsy. CONCLUSIONS: Our systematic review confirms the severe sequelae of IFD
in SLE. Cases occurred in patients with active SLE, who were on high daily
corticosteroids doses and at early stages of disease. This highlights the role of
poor disease control and a high "net state of immunosuppression" in risk. IFD in
SLE should be prospectively examined in the modern era.
PMID- 25129260
TI - Osseous sarcoidosis: clinical characteristics, treatment, and outcomes-
experience from a large, academic hospital.
AB - OBJECTIVE: Osseous sarcoidosis has been infrequently reported. We aimed to
characterize the distribution of lesions, clinical presentation, treatment, and
outcomes for osseous sarcoidosis. METHODS: Cases of osseous sarcoidosis were
identified by directed inquiry to clinicians and electronic query. Cases were
defined as having pathologic evidence of non-caseating granulomas on bone biopsy
or evidence of osseous lesions on imaging attributable to sarcoidosis in patients
with known sarcoidosis. Detailed characteristics were obtained by medical record
review. RESULTS: We identified a total of 20 cases of osseous sarcoidosis.
Osseous lesions were detected by imaging during the initial sarcoidosis
presentation in 60% of cases. In those who had a prior diagnosis of sarcoidosis,
the median duration of sarcoidosis before detection of osseous involvement was
4.3 years. Symptoms were present in 50% of cases. All cases had more than one
bone involved. The axial skeleton was involved in the majority of cases (90%),
primarily the pelvis and the lumbar spine. Most cases required no treatment
(55%); a minority of cases (45%) were treated, most often with prednisone,
methotrexate, or hydroxychloroquine. Two cases required multiple
immunosuppressants, including tumor necrosis factor inhibitors, for refractory
symptomatic osseous sarcoidosis. Treated cases were younger than those who were
untreated. At last follow-up, most cases (85%) were asymptomatic from osseous
lesions. CONCLUSIONS: In this case series of osseous sarcoidosis from a single
center, most patients had multiple bones affected and had other systemic
manifestations of sarcoidosis. A minority required treatment for relief of
symptoms, and most cases were asymptomatic at last follow-up.
PMID- 25129258
TI - Genetics of psychotropic medication induced side effects in two independent
samples of bipolar patients.
AB - The treatment of bipolar disorder (BD) usually requires combination therapies,
with the critical issue of the emergence of adverse drug reactions (ADRs) and the
possibility of low treatment adherence. Genetic polymorphisms are hypothesized to
modulate the pharmacodynamics of psychotropic drugs, representing potential
biological markers of ADRs. This study investigated genes involved in the
regulation of neuroplasticity (BDNF, ST8SIA2), second messenger cascades (GSK3B,
MAPK1, and CREB1), circadian rhythms (RORA), transcription (SP4, ZNF804A), and
monoaminergic system (HTR2A and COMT) in the risk of neurological, psychic,
autonomic, and other ADRs. Two independent samples of BD patients
naturalistically treated were included (COPE-BD n = 147; STEP-BD n = 659). In the
COPE-BD 34 SNPs were genotyped, while in the STEP-BD polymorphisms in the
selected genes were extracted from the genome-wide dataset. Each ADRs group was
categorized as absent-mild or moderate-severe and logistic regression with
appropriate covariates was applied to identify possible risk genotypes/alleles.
58.5 and 93.5 % of patients were treated with mood stabilizers, 44.2 and 50.7 %
were treated with antipsychotics, and 69.4 and 46.1 % were treated with
antidepressants in the COPE-BD and STEP-BD, respectively. Our findings suggested
that ST8SIA2 may be associated with psychic ADRs, as shown in the COPE-BD
(rs4777989 p = 0.0017) and STEP-BD (rs56027313, rs13379489 and rs10852173). A
cluster of RORA SNPs around rs2083074 showed an effect on psychic ADRs in the
STEP-BD. Trends supporting the association between HTR2A and autonomic ADRs were
found in both samples. Confirmations are needed particularly for ST8SIA2 and RORA
since the few available data regarding their role in relation to psychotropic
ADRs.
PMID- 25129261
TI - Is there a polysomnographic signature of augmentation in restless legs syndrome?
AB - OBJECTIVE: Augmentation of restless legs syndrome (RLS) is a potentially severe
side-effect of dopaminergic treatment. Data on objective motor characteristics in
augmentation are scarce. The aim of this study was to investigate in detail
different variables of leg movements (LM) in untreated, treated, and augmented
RLS patients. METHODS: Forty-five patients with idiopathic RLS [15 untreated, 15
treated (non-augmented), 15 augmented] underwent RLS severity assessment, one
night of video-polysomnography with extended electromyographic montage, and a
suggested immobilization test (SIT). RESULTS: Standard LM parameters as well as
periodicity index (PI) and muscle recruitment pattern did not differ between the
three groups. The ultradian distribution of periodic leg movements (PLM) in sleep
during the night revealed significant differences only during the second hour of
sleep (P <0.05). However, augmented patients scored highest on RLS severity
scales (P <0.05) and were the only group with a substantial number of PLM during
the SIT. CONCLUSION: This study demonstrates that polysomnography is of limited
usefulness for the diagnosis and evaluation of RLS augmentation. In contrast, the
SIT showed borderline differences in PLM, and differences on subjective scales
were marked. According to these results, augmentation of RLS is a phenomenon that
predominantly manifests in wakefulness.
PMID- 25129262
TI - Restless legs syndrome and central nervous system gamma-aminobutyric acid:
preliminary associations with periodic limb movements in sleep and restless leg
syndrome symptom severity.
AB - BACKGROUND: Previous research has demonstrated abnormalities in glutamate and N
acetyl aspartate (NAA) in the thalamus in individuals with restless legs syndrome
(RLS) compared with healthy matched controls. However, levels of these
transmitters in other RLS-related brain areas and levels of the most common
inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), have not been
assessed. METHODS: This study examined GABA, glutamate, and NAA levels in the
dorsal anterior cingulate cortex (ACC), thalamus and cerebellum with the use of
proton magnetic resonance spectroscopy ((1)H-MRS) at 4 tesla (4 T) and Megapress
difference-editing in 18 subjects with RLS and a matched control group without
RLS. Actigraphy was performed on the nights before scans to assess periodic limb
movements of sleep (PLMS). RESULTS: Levels of GABA, glutamate, and NAA were no
different between RLS and control subjects in any of the three voxels of
interest. However, GABA levels were positively correlated with both PLM indices
and RLS severity in the thalamus and negatively with both of these measures in
the cerebellum in RLS subjects. In addition, NAA levels were higher in the ACC in
RLS than in controls. CONCLUSION: Our preliminary data suggest that known
cerebellar-thalamic interactions may modulate the intensity of RLS sensory and
motor symptoms. In addition, anterior cingulate cortex may be associated with the
affective components of the painful symptoms in this disorder.
PMID- 25129263
TI - Coronary angioscopy and optical coherence tomography for confirmation of drug
coated neointimal plaque after paclitaxel-coated balloon angioplasty for in-stent
restenosis.
PMID- 25129264
TI - BDNF expression of macrophages and angiogenesis after myocardial infarction.
PMID- 25129265
TI - Coronary artery aneurysm formation within everolimus-eluting bioresorbable stent.
PMID- 25129267
TI - Cost-effectiveness analysis of Chagas' cardiomyopathy: early diagnosis and
prevention should be the target for comparison.
PMID- 25129266
TI - Meta-analysis of circulating 25-hydroxyvitamin D levels and risk of
cardiovascular and all-cause mortality in elderly population.
PMID- 25129268
TI - The effects of thiamine treatment on pre-diabetic versus overt diabetic rat
hearts: role of non-oxidative glucose pathways.
PMID- 25129269
TI - Intrinsic bleeding risk in patients with uninterrupted oral anticoagulation
undergoing cardiac implantable electronic device procedures: a pilot study.
PMID- 25129270
TI - Delay to diagnosis amongst patients with catecholaminergic polymorphic
ventricular tachycardia.
PMID- 25129271
TI - Determinants and implications of elevated soluble ST2 levels in heart failure.
PMID- 25129272
TI - Association of age and gender with anterior location of STEMI.
PMID- 25129273
TI - Is IL-10 a predictor of in-stent restenosis in stable and unstable angina
patients undergoing coronary interventions?
PMID- 25129274
TI - Resolution of acquired von Willebrand syndrome after transcatheter aortic valve
implantation through a left transcarotid approach.
PMID- 25129275
TI - Residual platelet reactivity after clopidogrel loading in ST-elevation myocardial
infarction patients undergoing a delayed catheterization. Impact on long term
clinical events.
PMID- 25129276
TI - Transthoracic echocardiographic backscatter-based assessment of left atrial
remodeling involving left atrial and ventricular fibrosis in patients with atrial
fibrillation.
PMID- 25129277
TI - The Anp genetic variant Rs5068 and circulating levels of natriuretic peptides in
patients with chronic heart failure.
PMID- 25129279
TI - Prevalence of overweight and obesity among children and adolescents is associated
with urbanization in Shandong, China.
PMID- 25129278
TI - Serum albumin changes and multivariate dynamic risk modelling in chronic heart
failure.
AB - BACKGROUND: We examined the prognostic utility of rate of change in serum albumin
over time in chronic heart failure (CHF), as well as the utility of multivariate
dynamic risk modelling. METHODS AND RESULTS: The survival implication of ?albumin
was analysed in 232 systolic CHF patients and validated in 212 patients. A
multivariate dynamic risk score predicated on the rate of change in 6 simple
indices including albumin was calculated and related to mortality. In derivation
patients, 50 (22%) deaths occurred over 13 months. Greater rates of decline in
albumin related to higher mortality (HR 0.55, 95% CI 0.41-0.73, P<0.0001)
independently, incrementally and more accurately than other covariates including
baseline albumin. A rate of attenuation >0.4 g/dL/month optimally forecasted
death and was associated with a 5-fold escalated risk of mortality (HR 5.13, 95%
CI 2.92-9.00, P<0.0001). Similar results were seen in the validation cohort. On
multivariate dynamic risk modelling, survival at 1-year worsened with higher
scores-a score >= 3 was associated with a 12-fold greater risk of death than a
score of 0, a 6-fold higher risk of death than a score of 1, and a 4-fold
enhanced risk of mortality than a score of 2. CONCLUSION: Attenuations in serum
albumin over time relate to increased mortality in CHF, and a risk model
predicated on the rate of change in 6 simple indices can identify patients at a
12-fold enhanced risk of death over the coming year.
PMID- 25129280
TI - Cardiovascular mortality and the financial crisis in Greece: trends and outlook.
PMID- 25129281
TI - Characterisation of novel cytokines in human atherosclerotic plaque.
PMID- 25129282
TI - Validation of rate of perceived exertion-based exercise training in patients with
heart failure: insights from autonomic nervous system adaptations.
AB - BACKGROUND: Exercise prescription in cardiac patients is based on heart rate (HR)
response to exercise. How to prescribe long-term exercise training outside
medically-supervised settings also considering changes in individual physical
capacity over time is unknown. In this study we hypothesized that in patients
with chronic heart failure (CHF) the session-rate of perceived exertion (RPE), a
subjective-based training methodology, provides autonomic and functional capacity
changes superimposable to those observed with HR-based Training Impulses (TRIMPi)
method. METHODS: Twenty patients with stable CHF were randomized to either
aerobic continuous training (ACT) or aerobic interval training (AIT) for 12
weeks. For each TRIMPi-guided exercise session, the session-RPE was recorded. By
this method, internal training load (TL) is quantified by multiplying the RPE of
the whole training session, using the Borg CR10-scale, by its duration. Heart
rate variability (HRV), and baroreflex sensitivity (BRS) were assessed at
baseline and at 3 weeks intervals. RESULTS: Significant correlations were found
between TRIMPi and individual session-RPE, for both ACT and AIT (r=0.63 to 0.81),
(P<0.05). The same occurred when ACT and AIT groups were pooled together (r=0.72;
P<0.01). R-R interval, HRV and BRS were significantly and very highly correlated
with weekly RPE-session (r(2) ranged from 0.77 to 0.97; P<0.001). A significant
relationship between session-RPE and performance at the 6MWT was also found.
CONCLUSIONS: Session-RPE is an easy-to-use, inexpensive and valid method for
exercise prescription and health maintenance, consistent with objective
physiological indices of training, that could be used for long-term physical
activity in patients with CHF.
PMID- 25129283
TI - In case of strict application, the third universal definition of myocardial
infarction will erase takotsubo syndrome as a diagnosis.
PMID- 25129284
TI - One of the causes of secondary cardiyomyopathies: diabetic cardiomyopathy.
PMID- 25129285
TI - Left ventricular hypertrophy and QTc dispersion are predictors of long-term
mortality in subjects with type 2 diabetes.
PMID- 25129286
TI - Coronary stent fracture mechanisms and clinical implications assessed by
multimodality imaging.
PMID- 25129287
TI - Electrical stimulation of the renal arterial nerves does not unmask the blindness
of renal denervation procedure in swine.
PMID- 25129288
TI - 6-year post-PCI follow-up of a 110-year myocardial infarction patient: a case
report.
PMID- 25129289
TI - Cardiotoxicity: anthracyclines and long term cancer survivors.
PMID- 25129290
TI - Electrocardiographic changes in young men with left-sided spontaneous
pneumothorax.
PMID- 25129292
TI - Atrial septal defect occluder for the distal re-entry tear in type B aortic
dissection.
PMID- 25129291
TI - Hemodynamic effects of Ivabradine in addition to dobutamine in patients with
severe systolic dysfunction.
AB - BACKGROUND: Dobutamine induced tachycardia increases myocardial oxygen
consumption and impairs ventricular filling. We hypothesized that Ivabradine may
be efficient to control dobutamine induced tachycardia. METHODS: We assessed the
effects of Ivabradine in addition to dobutamine in stable heart failure (HF)
patients (LVEF < 35%, n = 22, test population) and validated its effects in
refractory cardiogenic shock patients (n = 9, validation population) with
contraindication to cardiac assistance or transplant. In the test population (62
+/- 17 years, LVEF = 24 +/- 8%), systolic and diastolic function were assessed at
rest and under dobutamine [10 gamma/min], before and after Ivabradine [5mg per
os]. In the validation population (54 +/- 11 years, LVEF = 22 +/- 7%), Ivabradine
[5mg twice a day] was added to the dobutamine infusion. RESULTS: In the test
population, Ivabradine decreased heart rate [HR] at rest and during dobutamine
echocardiography (-9 +/- 8 bpm, P = 0.0004). The decrease in HR was associated
with a decrease in cardiac power output and an increase in diastolic duration at
rest (+ 74 +/- 67 ms, P = 0.0002), and during dobutamine infusion (+ 75 +/- 67
ms, P < 0.0001). Change in LVEF during dobutamine was greater after Ivabradine
treatment than before (+ 7.2 +/- 4.7% vs. + 3.6 +/- 4.2%, P = 0.002). In the
validation population, Ivabradine decreased HR (-18 +/- 11 bpm, P = 0.008) and
improved diastolic filling time (+ 67 +/- 42 ms, P = 0.012) without decreasing
cardiac output. At 24h, Ivabradine improved systolic blood pressure (+ 9 +/- 5
mmHg, P = 0.007), daily urine output (+ 0.7 +/- 0.5L, P = 0.008), oxygen balance
(DeltaScv02 = + 13 +/- 15%, P = 0.010), and NT-pro BNP (-2270 +/- 1912 pg/mL, P =
0.017). Finally, only 2/9 (22%) patients died whereas expected mortality
determined from a historical cohort was 78% (P = 0.017). CONCLUSION: This pilot
study demonstrates the safety and potential benefit of a HR lowering agent in
cardiogenic shock.
PMID- 25129293
TI - 10-year risk for atherosclerotic cardiovascular disease and coronary heart
disease among Korean adults: findings from the Korean National Health and
Nutrition Examination Survey 2009-2010.
AB - BACKGROUND: This study examined the distribution of the 10-year risk for
development of atherosclerotic cardiovascular disease (ASCVD) and coronary heart
disease (CHD), and the proportion of participants eligible for lipid management,
in the Korean population. METHODS: The risk was estimated using the Pooled Cohort
Equations for non-Hispanic Whites and the Adult Treatment Panel (ATP) III
equations. Eligibility for lipid-lowering treatment was assessed using the
American College of Cardiology/American Heart Association Blood Cholesterol
Guideline and the ATP III recommendation. Complex sampling design and area under
the receiver operator characteristic curve (AUC) were used. RESULTS: Among 7594
ASCVD-free Korean adults, aged 40-79 years, 31.3% (men, 44.1%; women, 19%) had a
10-year risk for an ASCVD event of >= 7.5%, and 27.1% (men, 39.4%; women, 15.2%)
had a 10-year risk for a CHD event of >= 10%. These proportions differed
according to age groups, ranging from 6.1 to 91.9% and 8.7 to 58.7% for patients
in their 40s-70s, using the ASCVD and CHD risk estimations, respectively.
Overall, 78.7% of individuals remain in the same risk stratum. Those eligible for
lipid management included 32.8% of the participants using the ACC/AHA Guideline
and 11.9% of those using the ATP III recommendation. In discriminating ASCVD,
AUCs for the ASCVD risk assessment method and the CHD risk assessment method were
0.70 and 0.64, respectively (P<0.001). CONCLUSIONS: The distribution of 10-year
ASCVD and CHD risk was different according to the risk assessment methods.
PMID- 25129294
TI - The electrocardiogram as a predictive tool for recovery from poor left
ventricular function following coronary revascularization.
PMID- 25129295
TI - Speckle tracking echocardiography in cardiac sarcoidosis.
PMID- 25129296
TI - Electrical alternans due to large bilateral pleural effusion without pericardial
effusion.
PMID- 25129297
TI - Bosentan treatment for pulmonary arterial hypertension due to patent ductus
arteriosus and Down's syndrome in an infant.
PMID- 25129298
TI - Effectiveness of switching 'low responders' to prasugrel to ticagrelor after
acute coronary syndrome.
PMID- 25129299
TI - Removal of an intracardiac lost port-A catheter utilizing a simple low-cost
method.
PMID- 25129300
TI - Obesity paradox in patients with atrial fibrillation and heart failure.
PMID- 25129301
TI - Are late potentials and fractionated electrocardiograms in patients with non
ischemic and ischemic cardiomyopathy wholly (or partially) due to repolarization
abnormalities?
PMID- 25129302
TI - Testosterone levels and heart failure in obese and non-obese men.
PMID- 25129303
TI - Left ventricular fibroma: what cardiac magnetic resonance imaging may add?
PMID- 25129304
TI - First report of stent thrombosis after a switch therapy resulting from ticagrelor
related dyspnea.
PMID- 25129305
TI - Utility of intra-aortic balloon pump support for multivessel coronary artery
spasm and cardiac arrest.
PMID- 25129306
TI - Intra-scar perfusion heterogeneity by cardiac magnetic resonance in a porcine
model of non-reperfused myocardial infarction.
PMID- 25129307
TI - Renal denervation: should we still hang in there?
PMID- 25129308
TI - Effects of weather on neurally mediated syncope tests.
PMID- 25129309
TI - Management of oral chronic pharmacotherapy in patients hospitalized for acute
decompensated heart failure.
AB - Acute decompensated heart failure (ADHF) is the most common cause of
cardiovascular hospitalization. The presentation is characterized by different
clinical profiles due to various underlying causes, volume balance and tissue
perfusion status. Currently, a variety of pharmacological therapies, including
diuretics, beta-blockers, ACE-inhibitors, angiotensin receptor blockers and
digoxin, are usually prescribed in order to treat chronic heart failure (HF)
syndromes caused by left ventricular systolic dysfunction. Despite the large
number of HF patients with frequent hospitalizations for decompensation, only a
few studies have evaluated the management of oral chronic therapies in the
clinical setting of ADHF. This article summarizes the information derived from
the few published trials on this subject and a therapeutic approach is suggested
with respect to the continuation, dose modification or suspension of oral
medications.
PMID- 25129310
TI - Circulating miR-222 in plasma and its potential diagnostic and prognostic value
in gastric cancer.
AB - Previous studies have revealed the significance of circulating microRNAs as
biomarkers for cancers. The aim of this study was to detect the levels of
circulating microRNA-222 (miR-222) in plasma of gastric cancer (GC) patients and
evaluate its diagnostic and prognostic value. Levels of circulating miR-222 were
detected by using qRT-PCR in plasma of 114 GC patients, 36 chronic atrophic
gastritis (CAG) patients and 56 healthy controls. The result showed that the
expression of circulating miR-222 in plasma was significantly upregulated in GC
compared with CAG and healthy controls (all at P < 0.001). And its high level was
significantly correlated with clinical stages (P < 0.001) and lymph nodes
metastasis (P = 0.009). The receiver operating characteristics (ROC) curve
analyses revealed that miR-222 had considerable diagnostic accuracy, yielded an
AUC (the areas under the ROC curve) of 0.850 with 66.1 % sensitivity and 88.3 %
specificity in discriminating GC from healthy controls. Moreover, Kaplan-Meier
analysis demonstrated a correlation between increased circulating miR-222 level
and reduced disease-free survival (P = 0.016) and overall survival (P = 0.012).
In multivariate analysis stratified for known prognostic variables, circulating
miR-222 was identified as an independent prognostic marker. In conclusion, our
findings suggested that circulating miR-222 in plasma might be a potential and
useful noninvasive biomarker for the early detection and prognosis of GC.
PMID- 25129311
TI - Expression of serum survivin protein in diagnosis and prognosis of gallbladder
cancer: a comparative study.
AB - The role of survivin in gallbladder cancer (GBC) has not been evaluated. We
investigated survivin protein expression in serum of patients with gallbladder
diseases (cholelithiasis, n = 30; GBC, n = 39) and compared with healthy controls
(n = 25). Clinicopathological parameters, diagnosis and prognosis of patients
with GBC were correlated with the expression of serum survivin by enzyme-linked
immunosorbent assay. Significantly higher (P < 0.0001) expression of survivin
protein was observed in GBC as compared to cholelithiasis and control. Increased
survivin expression was significantly associated with higher tumor stage (stage
III vs. stage II; P < 0.0001) and cellular differentiation (poor and moderate vs.
well differentiated; P < 0.0001) in GBC. No significant correlation was observed
with any of the other clinico-pathological parameters studied. The cutoff value
of survivin protein of 79 pg/ml with sensitivity of 81.16 % and specificity of 80
% differentiated the diseased group (cholelithiasis or GBC) from control group
were as the cutoff value of 109 pg/ml differentiated GBC from cholelithiasis with
a sensitivity of 82.05 % and specificity of 93.33 %. Though not significant,
increased expression of survivin was associated with median overall survival (12
vs. 18 months; P = 0.05) in GBC patients. Our study suggests that survivin
protein in serum could be both a useful diagnostic marker and an important
prognostic factor for GBC.
PMID- 25129312
TI - Diagnostic and prognostic significance of serum miR-24-3p in HBV-related
hepatocellular carcinoma.
AB - The aim of this study was to explore the diagnostic and prognostic value of serum
microRNAs (miRNAs) in hepatitis B viral (HBV)-related hepatocellular carcinoma
(HCC). We retrospectively analyzed clinical data of 84 consecutive patients with
HBV-related HCC who underwent curative resection. Additionally, we enrolled 46
healthy controls and 31 patients with chronic liver disease (CLD). Serum levels
of miR-155-5p, miR-24-3p, miR-490-3p, miR-210-3p, and miR-335-5p were measured.
Associations of serum miRNAs with clinicopathological factors were evaluated.
Receiver operating characteristic curves were established for discriminating HCC
patients from CLD patients, and the area under the curve (AUC) was calculated.
Overall survival (OS) and disease-free survival (DFS) were examined by the Kaplan
Meier method. Prognostic factors were determined by multivariate Cox analysis.
Consequently, serum miR-24-3p levels were significantly greater in HCC patients
than healthy controls and CLD patients. Serum miR-24-3p was significantly
associated with vascular invasion in HCC patients. Serum miR-24-3p discriminated
HCC patients from CLD, with an AUC of 0.636 [95 % confidence interval (CI) 0.524
0.748]. Combined serum alpha-fetoprotein (AFP) and miR-24-3p had an increased AUC
of 0.834 (95 % CI 0.745-0.923; P < 0.001). Elevated serum miR-24-3p was an
independent poor prognostic factor for OS and DFS of HCC patients. In conclusion,
the combination of serum miR-24-3p and AFP improves the diagnostic accuracy for
HCC prediction compared to each biomarker alone. High serum miR-24-3p level is an
independent predictor of poor OS and DFS in patients with HBV-related HCC.
PMID- 25129313
TI - Overexpression of fibrinogen-like protein 2 induces epithelial-to-mesenchymal
transition and promotes tumor progression in colorectal carcinoma.
AB - The main cause of death in colorectal carcinoma (CRC) patients is tumor
metastasis; however, the underlying molecular mechanisms are largely unknown. In
the present study, a novel metastasis-related gene, fibrinogen-like protein 2
(FGL2), was characterized for its role in CRC metastasis and underlying molecular
mechanisms. The clinical significance of FGL2 was investigated using tissue
microarray analysis of samples from 82 patients with CRC. The molecular effects
of FGL2 in CRC cells were determined using RNA interference and ectopic
expression of FGL2. The overexpression of FGL2 was examined by
immunohistochemistry in 82 CRC patients, and it was determined to be an
independent predictor of overall survival (P < 0.05). The depletion of FGL2
expression inhibited tumor progression and epithelial-to-mesenchymal transition
(EMT) in vitro and in vivo, while ectopic overexpression of FGL2 enhanced cell
invasion and induced EMT in vitro. Our results suggest that FGL2 plays an
important oncogenic role in CRC aggressiveness by inducing EMT, and FGL2 could be
employed as a novel prognostic marker and effective therapeutic target for CRC.
PMID- 25129314
TI - Action of nitroheterocyclic drugs against Clostridium difficile.
AB - The nitroheterocyclic classes of drugs have a long history of use in treating
anaerobic infections, as exemplified by metronidazole as a first-line treatment
for mild-to-moderate Clostridium difficile infection (CDI). Since direct
comparisons of the three major classes of nitroheterocyclic drugs (i.e.
nitroimidazole, nitazoxanide and nitrofurans) and nitrosating agents against C.
difficile are under-examined, in this study their actions against C. difficile
were compared. Results show that whilst transient resistance occurs to
metronidazole and nitazoxanide, stable resistance arises to nitrofurans upon
serial passage. All compounds killed C. difficile at high concentrations in
addition to the host defence nitrosating agent S-nitrosoglutathione (GSNO). This
suggests that GSNO killing of C. difficile contributes to its efficacy in murine
CDI. Although nitric oxide production could not be detected for the
nitroheterocyclic drugs, the cellular response to metronidazole and nitrofurans
has some overlap with the response to GSNO, causing significant upregulation of
the hybrid-cluster protein Hcp that responds to nitrosative stress. These
findings provide new insights into the action of nitroheterocyclic drugs against
C. difficile.
PMID- 25129316
TI - Carbapenem-resistant Enterobacter gergoviae harbouring blaKPC-2 in Brazil.
PMID- 25129317
TI - Mutant prevention concentrations of pradofloxacin for susceptible and mutant
strains of Escherichia coli with reduced fluoroquinolone susceptibility.
AB - Pharmacodynamic and mutant prevention properties of the fluoroquinolone
pradofloxacin (PRA) were measured against a set of 17 Escherichia coli strains
carrying no, one or two known mutations conferring reduced fluoroquinolone
susceptibility. The strains included susceptible wild-types, isogenic constructed
mutants, isogenic selected mutants and clinical isolates. The effectiveness of
PRA was determined with regard to preventing the selection of resistant mutants,
using static and changing concentrations of drug. Ciprofloxacin was used as a
reference drug. Minimum inhibitory concentrations (MICs) and mutant prevention
concentrations (MPCs) of PRA for the susceptible wild-type strains were in the
range 0.012-0.016mg/L and 0.2-0.3mg/L, respectively, giving a mean+/-standard
deviation mutant prevention index (MPI=MPC/MIC) of 17.7+/-1.1. The mean MPI PRA
of the 14 mutant strains was 19.2+/-12, and the mean MPI across all 17 strains
was 18.9+/-10.8. In an in vitro kinetic model in which PRA was diluted with a
half-life of 7h to mimic in vivo conditions, an initial concentration of PRA of
1.6-2.4mg/L (8-10* MPC), giving a PRA AUC/MPC ratio of 73-92, and a T>MPC of 21
23h was sufficient to prevent the selection of resistant mutants from the three
susceptible wild-type strains. Dosing to reduce selection for antibiotic
resistance in veterinary therapy has a role in reducing the reservoir of
resistant mutants. We conclude that a level of dosing that prevents the selection
of resistant mutants during therapy should be achievable in vivo.
PMID- 25129315
TI - Activity of echinocandins and triazoles against a contemporary (2012) worldwide
collection of yeast and moulds collected from invasive infections.
AB - In this study, 1717 fungal clinical isolates causing invasive fungal infections
were evaluated against nine antifungal agents using Clinical and Laboratory
Standards Institute (CLSI) reference broth microdilution methods. The isolates
comprised 1487 Candida spp., 109 Aspergillus spp., 86 non-Candida yeasts
(including 52 isolates of Cryptococcus neoformans) and 35 rare moulds obtained
during 2012 from 72 hospitals worldwide. Echinocandin resistance among Candida
spp. was low, and resistance rates to anidulafungin, caspofungin and micafungin
varied from 0.0% to 2.8% among different species. Echinocandin-resistant Candida
glabrata were shown to have fks mutations (fks2 HS1 F659Y, F659del, S663F and
S663P), and fluconazole resistance was also observed in those strains. One
Candida krusei and one Candida dubliniensis had L701M or S645P fks1 mutations,
respectively. Candida tropicalis and C. glabrata had higher fluconazole
resistance rates of 6.1% and 6.9%, respectively, compared with other Candida spp.
Fluconazole-resistant C. tropicalis were collected in five countries (USA, China,
Germany, Belgium and Thailand). Voriconazole was active against all Candida spp.,
inhibiting 91.2-99.7% of isolates using species-specific breakpoints. All agents
except for the echinocandins and posaconazole were active against Cr. neoformans.
Triazoles were active against other yeasts [MIC90 (minimum inhibitory
concentration encompassing 90% of isolates tested), 2MUg/mL]. The echinocandins
and the mould-active triazoles were active against Aspergillus [MIC/MEC90
(minimum effective concentration encompassing 90% of isolates tested) range,
0.015-2MUg/mL], but the activity of these agents was limited against uncommon
mould species (MIC/MEC90 range, 4MUg/mL to >16MUg/mL).
PMID- 25129318
TI - Neonatal candidiasis: diagnosis, prevention, and treatment.
AB - Infection with Candida species is associated with significant morbidity and
mortality in infants. The incidence of Candida infection varies widely across
centers, likely due to differences in practice related to modifiable risk factors
such as exposure to empiric antibiotics and length of parenteral nutrition. Early
diagnosis of Candida and prompt treatment with appropriate antifungal agents,
such as fluconazole, amphotericin B deoxycholate, and micafungin, are critical
for improved outcomes. This paper reviews the current literature relating to the
prevention, diagnosis, and treatment of Candida infections in the neonatal
intensive care unit.
PMID- 25129319
TI - [Practical management of neonatal sepsis risk in term or near-term infants].
AB - Incidence of neonatal early-onset sepsis has dramatically declined in France from
0.65 to 0.230/00 live births in 10 years since national guidelines to detect and
treat intrapartum women with group B streptococcus colonization have been
adopted. However, neonatal early-onset sepsis continues to be a common healthcare
burden. Group B streptococcus (GBS) remains the leading cause of bacterial
infection in term or near-term infants. As a result of prevention strategies,
approximately 30% of pregnant women and more than 2% of newborns are treated with
systemic antibiotics. Concerns have been expressed about the safety of wide use
of antibiotics such as antibiotic resistance, emergence of Escherichia coli
infections, and long-term side effects due to gut microbiota modifications. New
recommendations from the Centers of Disease Control in the United States and from
European countries aim at improving GBS detection methods, updating algorithms
for GBS intrapartum chemoprophylaxis in pregnant women, defining high-risk
newborns more efficiently, and limiting biological evaluation in low-risk
newborns.
PMID- 25129321
TI - The variation of HVL with focal spot to chamber distance as a function of beam
quality for the Pantak Therapax 150 X-ray unit and the implications on dose to
water determination using the IPEMB code of practice.
AB - Using a Pantak Therapax SXT 150 system HVL values for clinical beams generated
with filters 4-8, were determined as a function of FCD (30-130 cm). Aluminium
absorbers were placed midway between the focus and chamber with collimation to
define both narrow and broad beam geometries. For filters 4-7 with broad beam
geometry the HVL initially decreases as the FCD is increased from 30 cm and then
increases as the FCD approaches 130 cm. In contrast filter 8 exhibits a reduction
in HVL with increasing FCD attributed to the decreasing influence of absorber
scatter. With narrow beam geometry the HVL of filter 4 increases as the FCD is
increased. For other filters the HVL variation is similar to that for the broader
beam albeit that for a given FCD the HVL is smaller, a consequence of reduced
absorber scatter. Monte Carlo BEAMnrc simulations of filter 4-8 beams
demonstrated a quality dependent air attenuation effect associated with an
increase in HVL for lower quality beams with increasing FCD. Thus for the beams
investigated in this work the variation of HVL with FCD can be interpreted in
terms of the competing influences of absorber scatter, which tends to decrease
the measured HVL, and a quality dependent in air attenuation that tends to
increase the HVL with increasing FCD. In terms of an absorbed dose determination
it is shown that changes of HVL with FCD resulted in variations of D w,z = 0 < +/
0.5 %.
PMID- 25129320
TI - [Overdose or hypersensitivity to vitamin D?].
AB - Vitamin D intoxication with severe hypercalcemia is rare in the neonatal and
infancy period. Through nine cases of hypercalcemia, secondary to taking 600,000
units of vitamin D (Sterogyl((r))), a review of vitamin D requirements and
possible mechanisms of toxicity including hypersensitivity to this vitamin will
be discussed. We report nine cases of babies admitted to our department between
the ages of 25 and 105 days for treatment of severe dehydration. The pregnancies
were normal, with no incidents at delivery. Clinical signs were dominated by
weight loss, vomiting, and fever. Examination on admission revealed dehydration
whose degree ranged from 8 to 15% with preserved diuresis and loss weight between
100 and 1100 g. Laboratory tests objectified hypercalcemia between 113 and
235mg/L, hypercalciuria (urinary calcium/creatinine mmol/mmol >0.5), and a low
level of parathyroid hormone. The vitamin D values in nine patients were toxic
(344-749 nmol/L; normal >50 nmol/L; toxicity if >250 nmol/L). Abdominal
ultrasound objectified renal nephrocalcinosis in seven patients. The DNA study,
performed in eight patients, did not reveal a mutation of the vitamin D 24
hydroxylase gene (CYP24A1). The treatment consisted of intravenous rehydration
with treatment of hypercalcemia (diuretics and corticosteroids). Serum calcium
returned to the normal range within 4-50 days, with weight gain progressively
over the following weeks. The follow-up (2 years for the oldest case) showed the
persistence of images of nephrocalcinosis. Genetic susceptibility and metabolic
differences appear to modulate the threshold of vitamin D toxicity. However,
respect for recommended doses, recognized as safe in a large study population,
reduces the risk of toxicity.
PMID- 25129322
TI - [Acute stent thrombosis and reverse transient left ventricular dilatation after
performing a single-photon emission computed tomography myocardial perfusion].
AB - A 63-year-old male patient with a history of stent implantation in the left
anterior descending three months before. Due to the presentation of vegetative
symptoms, he was referred for gated-SPECT myocardial perfusion. During
acquisition of the resting images he presented chest pain and ST segment
elevation, so that urgent cardiac catheterization was performed, showing stent
thrombosis. Rest perfusion imaging showed a defect in anterior and apical
perfusion, more severe and extensive than in the stress images, with striking
left ventricular dilatation and a fall in the ejection fraction related to the
acute ischemia phenomenon. Intense exercise is associated with a transient
activation of the coagulation system and hemodynamic changes that might induce
thrombosis, especially in recently implanted coronary stents that probably still
have not become completely endothelialized.
PMID- 25129323
TI - The structure and demographic correlates of cancer fear.
AB - BACKGROUND: Cancer is often described as the 'number one' health fear, but little
is known about whether this affects quality of life by translating into high
levels of worry or distress in everyday life, or which population groups are most
affected. This study examined the prevalence of three components of cancer fear
in a large community sample in the UK and explored associations with demographic
characteristics. METHODS: Questions on cancer fear were included in a survey
mailed to a community sample of adults (n = 13,351; 55-64 years). Three items
from a standard measure of cancer fear assessed: i) whether cancer was feared
more than other diseases, ii) whether thinking about cancer caused discomfort,
and iii) whether cancer worry was experienced frequently. Gender, marital status,
education, and ethnicity were assessed with simple questions. Anxiety was
assessed with the brief STAI and a standard measure of self-rated health was
included. RESULTS: Questionnaire return rate was 60% (7,971/13,351). The majority
of respondents agreed or strongly agreed that they feared cancer more than other
diseases (59%), and felt uncomfortable thinking about it (52%), and a quarter
(25%) worried a lot about cancer. All items were significantly inter-correlated
(r = .35 to .42, p's < .001), and correlated with general anxiety (r = .16 to
.28, p's < .001) and self-rated health (r = -.07 to -.16, p's < .001). In
multivariable analyses including anxiety and general health, all cancer fear
indicators were significantly higher in women (ORs between 1.15 and 1.48),
respondents with lower education (ORs between 1.40 and 1.66), and those with
higher general anxiety (ORs between 1.50 and 2.11). Ethnic minority respondents
(n = 285; 4.4%) reported more worry (OR: 1.85). CONCLUSIONS: More than half of
this older adult sample in the UK had cancer as greatest health fear and this was
associated with feeling uncomfortable thinking about it and worrying more about
it. Women and respondents with less education or from ethnic minority backgrounds
were disproportionately affected by cancer fear. General anxiety and poor health
were associated with cancer fear but did not explain the demographic differences.
PMID- 25129324
TI - Radioactive and chemical contamination of the water resources in the former
uranium mining and milling sites of Mailuu Suu (Kyrgyzstan).
AB - An assessment of the radioactive and chemical contamination of the water
resources at the former uranium mines and processing sites of Mailuu-Suu, in
Kyrgyzstan, was carried out. A large number of water samples were collected from
the drinking water distribution system (DWDS), rivers, shallow aquifers and
drainage water from the mine tailings. Radionuclides and trace metal contents in
water from the DWDS were low in general, but were extremely high for Fe, Al and
Mn. These elements were associated with the particle fractions in the water and
strongly correlated with high turbidity levels. Overall, these results suggest
that water from the DWDS does not represent a serious radiological hazard to the
Mailuu Suu population. However, due to the high turbidities and contents of some
elements, this water is not good quality drinking water. Water from artesian and
dug wells were characterized by elevated levels of U (up to 10 MUg/L) and some
trace elements (e.g. As, Se, Cr, V and F) and anions (e.g. Cl(-), NO3(-), SO4(2
)). In two artesian wells, the WHO guideline value of 10 MUg/L for As in water
was exceeded. As the artesian wells are used as a source of drinking water by a
large number of households, special care should be taken in order to stay within
the WHO recommended guidelines. Drainage water from the mine tailings was as
expected highly contaminated with many chemicals (e.g. As) and radioactive
contaminants (e.g. U). The concentrations of U were more than 200 times the WHO
guideline value of 30 MUg/L for U in drinking water. A large variation in
(234)U/(238)U isotopic ratios in water was observed, with values near equilibrium
at the mine tailings and far from equilibrium outside this area (reaching ratios
of 2.3 in the artesian well). This result highlights the potential use of this
ratio as an indicator of the origin of U contamination in Mailuu Suu.
PMID- 25129326
TI - Obesity: a certain and avoidable cause of cancer.
PMID- 25129325
TI - Gastric residual evaluation in preterm neonates: a useful monitoring technique or
a hindrance?
AB - It is routine practice in most neonatal intensive care units to measure the
volume and color of gastric residuals (GRs) prior to enteral bolus feedings in
preterm very low birth weight infants. However, there is paucity of evidence
supporting the routine use of this technique. Moreover, owing to the lack of
uniform standards in the management of GRs, wide variations exist as to what
constitutes significant GR volume, the importance of GR color and frequency of GR
evaluation, and the color or volume standards that dictate discarding or
returning GRs. The presence of large GR volumes or green-colored residuals prior
to feeding often prompts subsequent feedings to be withheld or reduced because of
possible necrotizing enterocolitis resulting in delays in enteral feeding.
Cessation or delays in enteral feeding may result in extrauterine growth
restriction, a known risk factor for poor neurodevelopmental and growth outcomes
in preterm very low birth weight infants. Although some neonatal intensive care
units are abandoning the practice of routine GR evaluation, little evidence
exists to support the discontinuation or continuation of this practice. This
review summarizes the current state of GR evaluation and underlines the need for
a scientific basis to either support or refute the routine evaluation of GRs.
PMID- 25129327
TI - Africa's child demographics and the world's future.
PMID- 25129328
TI - Body-mass index and risk of 22 specific cancers: a population-based cohort study
of 5.24 million UK adults.
AB - BACKGROUND: High body-mass index (BMI) predisposes to several site-specific
cancers, but a large-scale systematic and detailed characterisation of patterns
of risk across all common cancers adjusted for potential confounders has not
previously been undertaken. We aimed to investigate the links between BMI and the
most common site-specific cancers. METHODS: With primary care data from
individuals in the Clinical Practice Research Datalink with BMI data, we fitted
Cox models to investigate associations between BMI and 22 of the most common
cancers, adjusting for potential confounders. We fitted linear then non-linear
(spline) models; investigated effect modification by sex, menopausal status,
smoking, and age; and calculated population effects. FINDINGS: 5.24 million
individuals were included; 166,955 developed cancers of interest. BMI was
associated with 17 of 22 cancers, but effects varied substantially by site. Each
5 kg/m(2) increase in BMI was roughly linearly associated with cancers of the
uterus (hazard ratio [HR] 1.62, 99% CI 1.56-1.69; p<0.0001), gallbladder (1.31,
1.12-1.52; p<0.0001), kidney (1.25, 1.17-1.33; p<0.0001), cervix (1.10, 1.03
1.17; p=0.00035), thyroid (1.09, 1.00-1.19; p=0.0088), and leukaemia (1.09, 1.05
1.13; p<=0.0001). BMI was positively associated with liver (1.19, 1.12-1.27),
colon (1.10, 1.07-1.13), ovarian (1.09, 1.04-1.14), and postmenopausal breast
cancers (1.05, 1.03-1.07) overall (all p<0.0001), but these effects varied by
underlying BMI or individual-level characteristics. We estimated inverse
associations with prostate and premenopausal breast cancer risk, both overall
(prostate 0.98, 0.95-1.00; premenopausal breast cancer 0.89, 0.86-0.92) and in
never-smokers (prostate 0.96, 0.93-0.99; premenopausal breast cancer 0.89, 0.85
0.94). By contrast, for lung and oral cavity cancer, we observed no association
in never smokers (lung 0.99, 0.93-1.05; oral cavity 1.07, 0.91-1.26): inverse
associations overall were driven by current smokers and ex-smokers, probably
because of residual confounding by smoking amount. Assuming causality, 41% of
uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be
attributable to excess weight. We estimated that a 1 kg/m(2) population-wide
increase in BMI would result in 3790 additional annual UK patients developing one
of the ten cancers positively associated with BMI. INTERPRETATION: BMI is
associated with cancer risk, with substantial population-level effects. The
heterogeneity in the effects suggests that different mechanisms are associated
with different cancer sites and different patient subgroups. FUNDING: National
Institute for Health Research, Wellcome Trust, and Medical Research Council.
PMID- 25129330
TI - Finding the Twitter users who stood with Wendy.
AB - OBJECTIVE: I examine Twitter discussion regarding the Texas omnibus abortion
restriction bill before, during and after Wendy Davis' filibuster in summer 2013.
This critical moment precipitated wide public discussion of abortion. Digital
records allow me to characterize the spatial distribution of participants in
Texas and the United States and estimate the proportion of participants who were
Texans. STUDY DESIGN: Building a dataset based on all hashtags associated with
the bill between June 19th and July 14th, 2013, I use GPS locations and text
descriptions of locations to classify users by county of residence. Mapping
tweets from accounts within the continental United States by day, I describe the
residential composition of the conversation in total and over time. Using
indirect estimation, I compute an estimate of the number of Texans who
participated. RESULTS: About 1.66 million tweets were sent using hashtags
associated with the bill from 399,081 user accounts. I estimate counties of
residence for 160,954 participants (40.3%). An estimated 115,500 participants
(29%) were Texans, and Texans sent an estimated 48.8% of all tweets. Tweets were
sent from users estimated to live in every region of Texas, including 189 of
Texas' 254 counties. Texans tweeted more than non-Texans on every day except the
filibuster and the day after. CONCLUSION: The analysis measures real-life
responses to proposed abortion restrictions from people across Texas and the
United States. It demonstrates that Twitter users from across Texas counties
opposed HB2 by describing the geographical range of US and Texan abortion rights
supporters on Twitter. IMPLICATIONS: The Twitter discussion surrounding Wendy
Davis' filibuster revealed a geographically diverse population of individuals who
strongly oppose abortion restrictions. Texans from across the state were among
those who actively voiced opposition. Identifying rights supporters through
online behavior may present a new way of classifying individuals' orientations
regarding abortion rights.
PMID- 25129329
TI - Unmet demand for highly effective postpartum contraception in Texas.
AB - OBJECTIVES: We aimed to assess women's contraceptive preferences and use in the
first 6 months after delivery. The postpartum period represents a key opportunity
for women to learn about and obtain effective contraception, especially since 50%
of unintended pregnancies to parous women occur within 2 years of a previous
birth. METHODS: We conducted a prospective cohort study of 800 postpartum women
recruited from three hospitals in Austin and El Paso, TX. Women aged 18-44 who
wanted to delay childbearing for at least 24 months were eligible for the study
and completed interviews following delivery and at 3 and 6 months postpartum.
Participants were asked about the contraceptive method they were currently using
and the method they would prefer to use at 6 months after delivery. RESULTS: At 6
months postpartum, 13% of women were using an intrauterine device or implant, and
17% were sterilized or had a partner who had had a vasectomy. Twenty-four percent
were using hormonal methods, and 45% relied on less effective methods, mainly
condoms and withdrawal. Yet 44% reported that they would prefer to be using
sterilization, and 34% would prefer to be using long-acting reversible
contraception (LARC). CONCLUSIONS: This study shows a considerable preference for
LARC and permanent methods at 6 months postpartum. However, there is a marked
discordance between women's method preference and actual use, indicating
substantial unmet demand for highly effective methods of contraception.
IMPLICATIONS: In two Texas cities, many more women preferred long-acting and
permanent contraceptive methods (LAPM) than were able to access these methods at
6 months postpartum. Women's contraceptive needs could be better met by
counseling about all methods, by reducing cost barriers and by making LAPM
available at more sites.
PMID- 25129332
TI - Antibacterial activities of nemonoxacin against clinical isolates of
Staphylococcus aureus: an in vitro comparison with three fluoroquinolones.
AB - In comparison with ciprofloxacin, levofloxacin and moxifloxacin, antimicrobial
activity of nemonoxacin against ciprofloxacin-susceptible/-resistant methicillin
susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus
aureus (MRSA) was determined with the availability to select resistant mutants
evaluated. Minimum inhibitory concentrations and mutant prevention concentrations
of quinolones were determined by agar dilution method, that concentrated
bacterial cells were spread onto Mueller-Hinton agar plates containing
antibacterials at different concentrations. Selection index (SI) was calculated.
Minimum inhibitory concentration and mutant prevention concentration of
nemonoxacin were 0.063 and 0.25 MUg/mL for ciprofloxacin-susceptible MSSA and
those were 0.5 and 4.0 MUg/mL for ciprofloxacin-resistant MSSA, lower than
observations of three fluoroquinolones distinctly. SI of nemonoxacin and
moxifloxacin were similar, with narrower mutant selective window than
levofloxacin and ciprofloxacin. Minimum inhibitory concentration and mutant
prevention concentration of nemonoxacin were 0.25 and 2.0 MUg/mL for
ciprofloxacin-susceptible MRSA, which were 0.5 and 16.0 MUg/mL for ciprofloxacin
resistant MRSA. Values were lower than those determined from fluoroquinolones.
Nemonoxacin presents good antimicrobial activity against clinical isolates of S.
aureus, especially for ciprofloxacin-resistant strains. But stepwise mutant
accumulation of ciprofloxacin-resistant MRSA can be hardly inhibited by
nemonoxacin with pharmacokinetic parameters considered.
PMID- 25129331
TI - Colorectal cancer with potentially resectable hepatic metastases: optimizing
treatment.
AB - Colorectal cancer is a common malignancy and often presents with synchronous or
metachronous distant spread. For patients with hepatic metastases, resection is
the principal curative option. Liberalization of the indications for hepatic
resection has introduced a number of challenges related to the size,
distribution, and number of metastases as well as the condition of the future
liver remnant. Advances in systemic therapy have solidified its role as both an
important adjunct to surgery and also for many patients as a mechanism to
facilitate resection. In patients whose disease is marginally resectable as a
consequence of the distribution of hepatic lesions that precludes complete
resection or out of concern for the future liver remnant, a number of strategies
have been advocated, including prehepatectomy systemic therapy, staged surgical
approaches, ablative technologies, and preoperative portal vein embolization. It
is the purpose of this review to discuss ways in which to optimize the treatment
of patients with potentially resectable disease, specifically those who are
judged to have "borderline" resectable situations.
PMID- 25129333
TI - Providing Rapid Out of Hospital Acute Cardiovascular Treatment 3 (PROACT-3).
AB - BACKGROUND: The outcomes of acute cardiovascular symptom presentations are
potentially modifiable with the use of biomarkers to accelerate accurate
diagnosis. This randomized trial tested troponin and B-type natriuretic peptide
before hospital guidance in patients with acute cardiovascular symptoms. METHODS:
Patients with either chest pain or shortness of breath were randomized to usual
care or biomarkers analyzed using a point-of-care device in the ambulance. The
primary end point was time to final disposition (discharge from the emergency
department or admission to hospital). The trial was stopped prematurely because
of less than expected enrollment of patients of interest and no difference in the
primary end point. RESULTS: We randomized 491 patients; 480 formed the final
cohort. Patients were 49% male; median age 70 years; 42% had previous acute
coronary syndrome; and 28% diabetes. The B-type natriuretic peptide level before
hospital arrival was >= 100 pg/mL in 36.4%. Troponin was > 0.03 ng/mL in 13.4%;
3.6% had troponin > 0.1 ng/mL. After adjudication, 16% had acute coronary
syndrome, 6.5% acute heart failure, 3.3% angina, and 74.2% another diagnosis. The
primary end point was 9.2 (interquartile range, 7.3-11.1) hours in the biomarker
group and 8.8 (interquartile range, 6.3-12.1) hours in the usual care group (P =
0.6). None died in the ambulance or in the emergency department: all-cause 30-day
mortality was 2.1% (usual care) and 1.7% (biomarker). CONCLUSIONS: To our
knowledge, this is the first randomized trial of biomarkers before hospital
arrival to guide emergency management of suspected acute cardiovascular disease
which showed no benefit and was terminated early because of futility. The results
have important implications for the use of biomarkers in emergency management of
heart disease and for the design of future randomized trials on this important
topic.
PMID- 25129334
TI - Case report: protein-losing enteropathy caused by Mesocestoides vogae (syn. M.
corti) in a dog.
AB - An eight-year-old, neutered, female Shetland Sheepdog presented with a 6-week
history of small intestinal diarrhea. Regenerative anemia, hypoproteinemia, and
an increased plasma C-reactive protein concentration were detected on blood
examination. Fecal examination and abdominal radiography were unremarkable.
Abdominal ultrasonography showed diffusely hyperechoic mucosa in the small
intestine. Gastroduodenoscopy, performed under general anesthesia, revealed
mucosal edema and increased granularity in the duodenum and jejunum.
Histopathological examination of the endoscopically biopsied small intestinal
mucosa revealed tapeworm infection. A single administration of a combined
anthelmintic drug (5mg/kg praziquantel, 14.4 mg/kg pyrantel pamoate, and 15 mg/kg
febantel) was successful for deworming, and the dog fully recovered. The
parasites were removed from stored frozen duodenal mucosa and morphologically
identified as Mesocestoides sp. immature adult worms. Mitochondrial (mt) 12S rDNA
and mt cytochrome c oxide subunit 1 genes were amplified from the parasites. DNA
sequence analysis showed that the genes shared 100% identity with those of
reported M. vogae (syn. M. corti). This is the first reported case of protein
losing enteropathy caused by M. vogae in a dog.
PMID- 25129335
TI - Evaluation of a novel dried blood spot collection device (HemaSpotTM) to test
blood samples collected from dogs for antibodies to Leishmania infantum.
AB - Collection of blood samples from veterinary and wildlife patients is often
challenging because the samples have to be collected on farm or in the wild under
various environmental conditions. This poses many technical problems associated
with venipuncture materials, their safe use and disposal, transportation and
processing of collected samples. Dried blood spot (DBS) sample collection
techniques offer a simple and practical alternative to traditional blood
collection methods to obtain blood samples from animals for parasite antibody
evaluation. The DBS collection devices are compact, simple to use, and are
particularly useful for large number of samples. Additionally, DBS samples take
up less space and they are easier to transport than traditional venipuncture
collected blood samples. Visceral leishmaniasis (VL) is a potentially fatal
parasitic disease of dogs and humans and it is frequently diagnosed by antibody
tests. Immunochromatographic tests (ICT) for antibodies to Leishmania infantum
are commercially available for dogs and they produce qualitative results in
minutes. Measurement of canine antibodies to L. infantum with the ICT using
traditional venipuncture has been validated previously, but the use of DBS
samples has not been evaluated using this method. The purpose of the present
study was to determine the ability of DBS samples to detect antibodies to L.
infantum in dogs using a commercial ICT assay. One hundred plasma samples from
dogs experimentally infected with the LIVT-1 strain of L. infantum were collected
by venipuncture and frozen. Individual samples were thawed, and then 80 MUl
plasma (2 drops) was aliquotted onto the 8-spoked disk pad on individual DBS
sample collection devices (HemaSpotTM, Spot-On Sciences, Austin, TX), dried, and
stored in the dark at room temperature. After one month and six months,
respectively, 2 spokes of the 8 spokes of the disk pad of each DBS sample were
removed and eluted in 200 MUl PBS. The eluate was used to test for antibodies in
the ICT and compared to ICT results using thawed plasma (same initial source).
Sensitivity and specificity of the ICT using DBS were determined by using ICT
results from traditional blood collection samples for comparison. After 1 month,
DBS samples showed 100% sensitivity and specificity when compared to ICT results
on thawed plasma samples collected by traditional venipuncture. After six months
storage at room temperature, DBS samples demonstrated 79% sensitivity and 100%
specificity compared to traditional blood collection. Results from this study
indicate that dried blood spot collection may be a useful tool for screening dogs
for antibodies to L. infantum with the ICT assay.
PMID- 25129336
TI - DNA fluorescence shift sensor: a rapid method for the detection of DNA
hybridization using silver nanoclusters.
AB - DNA-templated silver nanoclusters (AgNC) are a class of subnanometer sized
fluorophores with good photostability and brightness. It has been applied as a
diagnostic tool mainly for deoxyribonucleic acid (DNA) detection. Integration of
DNA oligomers to generate AgNCs is interesting as varying DNA sequences can
result in different fluorescence spectra. This allows a simple fluorescence
shifting effect to occur upon DNA hybridization with the hybridization efficiency
being a pronominal factor for successful shifting. The ability to shift the
fluorescence spectra as a result of hybridization overcomes the issue of
background intensities in most fluorescent based assays. Here we describe an
optimized method for the detection of single-stranded and double-stranded
synthetic forkhead box P3 (FOXP3) target by hybridization with the DNA
fluorescence shift sensor. The system forms a three-way junction by successful
hybridization of AgNC, G-rich strand (G-rich) to the target DNA, which generated
a shift in fluorescence spectra with a marked increase in fluorescence intensity.
The DNA fluorescence shift sensor presents a rapid and specific alternative to
conventional DNA detection.
PMID- 25129337
TI - Electrodialytic remediation of polychlorinated biphenyls contaminated soil with
iron nanoparticles and two different surfactants.
AB - Polychlorinated biphenyls (PCB) are persistent organic pollutants (POP) that
strongly adsorb in soils and sediments. There is a need to develop new and cost
effective solutions for the remediation of PCB contaminated soils. The suspended
electrodialytic remediation combined with zero valent iron nanoparticles (nZVI)
could be a competitive alternative to the commonly adapted solutions of
incineration or landfilling. Surfactants can enhance the PCB desorption,
dechlorination, and the contaminated soil cleanup. In this work, two different
surfactants (saponin and Tween 80) were tested to enhance PCB desorption and
removal from a soil sampled at a polluted site, in a two-compartment cell where
the soil was stirred in a slurry with 1% surfactant, 10mL of nZVI commercial
suspension, and a voltage gradient of 1Vcm(-1). The highest PCB removal was
obtained with saponin. Higher chlorinated PCB congeners (penta, hexa, hepta and
octachlorobiphenyl) showed removal percentages between 9% and 96%, and the
congeners with highest removal were PCB138, PCB153 and PCB180. The use of low
level direct current enhanced PCB removal, especially with saponin.
Electrodechlorination of PCB with surfactants and nZVI showed encouraging
tendencies and a base is thus formed for further optimization towards a new
method for remediation of PCB polluted soils.
PMID- 25129338
TI - Impact of alcohols on the formation and stability of protein-stabilized
nanoemulsions.
AB - Nanoemulsions are increasingly being used for encapsulation, protection, and
delivery of bioactive lipids, however, their formation from natural emulsifiers
is still challenging. We investigated the impact of alcohol on the formation and
stability of protein-stabilized oil-in-water nanoemulsions prepared by high
pressure homogenization. The influence of different alcohols (ethanol, 1
propanol, and 1-butanol) at various concentrations (0-25% w/w) on the formation
and stability of emulsions stabilized by sodium caseinate, whey protein isolate,
and fish gelatin was investigated. The mean particle diameter decreased with
increasing alcohol concentrations from 0 to 10%w/w, but extensive droplet
aggregation occurred at higher levels. This phenomenon was attributed to enhanced
protein-protein interactions between the adsorbed emulsifier molecules in the
presence of alcohol leading to droplet flocculation. The smallest droplets
(d<100nm) were obtained when 10%w/w 1-butanol was added to sodium caseinate
stabilized nanoemulsions, but relatively small droplets (d<150nm) could also be
obtained in the presence of a food-grade alcohol (ethanol). This study
demonstrated that alcohol addition might be a useful tool for producing protein
stabilized nanoemulsions suitable for use as delivery systems of lipophilic
bioactive agents.
PMID- 25129339
TI - Short-term impact of pictorial posters and a crash course on radiographic errors
for improving the quality of paediatric chest radiographs in an unsupervised unit
- a pilot study for quality-assurance outreach.
AB - BACKGROUND: Chest radiography is the most commonly performed diagnostic X-ray
examination. The radiation dose to the patient for this examination is relatively
low but because of its frequent use, the contribution to the collective dose is
considerable. Optimized image quality not only allows for more accurate diagnosis
but also supports radiation protection, which is particularly important in
children. OBJECTIVE: To determine whether the introduction of a poster of
technical errors in paediatric radiography accompanied by a short lecture (crash
course) for radiographers on common errors can sustainably decrease the number
and rate of these errors in an unsupervised radiology department (without a
paediatric-trained radiologist or paediatric-trained radiography personnel).
MATERIALS AND METHODS: We conducted a pilot study for quality-assurance outreach,
with retrospective and prospective components, in the paediatric radiology
department of a teaching hospital. The technical errors in frontal chest
radiographs performed in the unit were assessed by quality-assurance analysis
using a customized tick-sheet. The review was performed before and after an
intervention that involved a half-hour crash course and poster displays in the
department. We compared the rate of technical errors made before and after the
intervention. RESULTS: There was statistically significant improvement in quality
of radiographs (P < 0.0083) performed immediately after the intervention. There
was a statistically significant decline in the quality of radiographs performed
>2 months after the intervention. CONCLUSION: A simple intervention of a crash
course and poster placement resulted in improved quality of paediatric chest
radiographs. A decline in quality after 2 months suggests the need to repeat this
or another type of intervention regularly.
PMID- 25129340
TI - MR Imaging in a case of severe anorexia nervosa: the 'flip-flop' effect.
AB - We report an MR imaging phenomenon that can lead to misinterpretation. The unique
appearance of the soft tissues and bone marrow in a 19-year-old severely
malnourished woman with anorexia nervosa raised concerns about technical failure
or systemic pathology. Due to extreme fat depletion, the T1-weighted images
appeared to be fat-suppressed and the fat-suppressed fluid-sensitive images
appeared to be non-fat-suppressed ("flip-flopped"). Failure to recognize the
influence of a patient's overall nutritional status on MR images may cause
confusion and misdiagnosis.
PMID- 25129341
TI - Assessing response in breast cancer with dynamic contrast-enhanced magnetic
resonance imaging: are signal intensity-time curves adequate?
AB - Quantitative DCE-MRI parameters including K(trans) (transfer constant min(-1))
can predict both response and outcome in breast cancer patients treated with
neoadjuvant chemotherapy (NAC). Quantitative methods are time-consuming to
calculate, requiring expensive software and interpretive expertise. For
diagnostic purposes, signal intensity-time curves (SITCs) are used for tissue
characterisation. In this study, we compare the ability of NAC-related changes in
SITCs with K(trans) to predict response and outcomes. 73 women with primary
breast cancer underwent DCE-MRI studies before and after two cycles of NAC.
Patients received anthracycline and/or docetaxel-based chemotherapy. At
completion of NAC, patients had local treatment with surgery & radiotherapy and
further systemic treatments. SITCs for paired DCE-MRI studies were visually
scored using a five-curve type classification schema encompassing wash-in and
wash-out phases and correlated with K(trans) values and to the endpoints of
pathological response, OS and DFS. 58 paired patients studies were evaluable. The
median size by MRI measurement for 52 tumours was 38 mm (range 17-86 mm) at
baseline and 26 mm (range 10-85 mm) after two cycles of NAC. Median baseline
K(trans) (min(-1)) was 0.214 (range 0.085-0.469), and post-two cycles of NAC was
0.128 (range 0.013-0.603). SITC shapes were significantly related to K(trans)
values both before (chi (2) = 43.3, P = 0.000) and after two cycles of NAC (chi
(2) = 60.5, P = 0.000). Changes in curve shapes were significantly related to
changes in K(trans) (chi (2) = 53.5, P = 0.000). Changes in curve shape were
significantly correlated with clinical (P = 0.005) and pathological response (P =
0.005). Reductions in curve shape of >=1 point were significant for overall
improved survival using Kaplan-Meier analysis with a 5-year OS of 80.9 versus
68.6 % (P = 0.048). SITCs require no special software to generate and provide a
useful method of assessing the effectiveness of NAC for primary breast cancer.
PMID- 25129342
TI - Transcriptional repression of ER through hMAPK dependent histone deacetylation by
class I HDACs.
AB - Anti-estrogen therapies are not effective in ER- breast cancers, thus identifying
mechanisms underlying lack of ER expression in ER- breast cancers is imperative.
We have previously demonstrated that hyperactivation of MAPK (hMAPK) downstream
of overexpressed EGFR or overexpression/amplification of Her2 represses ER
protein and mRNA expression. Abrogation of hMAPK in ER- breast cancer cell lines
and primary cultures causes re-expression of ER and restoration of anti-estrogen
responses. This study was performed to identify mechanisms of hMAPK-induced
transcriptional repression of ER. We found that ER promoter activity is
significantly reduced in the presence of hMAPK signaling, yet did not identify
specific promoter sequences responsible for this repression. We performed an
epigenetic compound screen in an ER- breast cancer cell line that expresses hMAPK
yet does not exhibit ER promoter hypermethylation. A number of HDAC inhibitors
were identified and confirmed to modulate ER expression and estrogen signaling in
multiple ER- cell lines and tumor samples lacking ER promoter methylation. siRNA
mediated knockdown of HDACs 1, 2, and 3 reversed the mRNA repression in multiple
breast cancer cell lines and primary cultures and ER promoter-associated histone
acetylation increased following MAPK inhibition. These data implicate histone
deacetylation downstream of hMAPK in the observed ER mRNA repression associated
with hMAPK. Importantly, histone deacetylation appears to be a common mechanism
in the transcriptional repression of ER between ER- breast cancers with or
without ER promoter hypermethylation.
PMID- 25129343
TI - High NR2F2 transcript level is associated with increased survival and its
expression inhibits TGF-beta-dependent epithelial-mesenchymal transition in
breast cancer.
AB - NR2F2, a member of nuclear receptor subfamily 2, was shown to be associated with
cancer, but its role in breast malignancy remains unclear. In this study, we
aimed to explore the function of NR2F2 in breast cancer. We browsed GEO and TCGA
databases and used Kaplan-Meier survival analysis to explore the association
between NR2F2 transcript level and patient survival in breast cancer. NR2F2
expression in breast cancer tissues was evaluated by immunohistochemistry
staining. NR2F2-related functions and its role in Epithelial-Mesenchymal
Transition (EMT) were predicted by Gene Set Enrichment Analysis (GSEA) and
validated by in vitro assays with NR2F2 knockdown MDA-MB231 and MCF7 cells. We
found high NR2F2 transcript level was correlated with favorable overall survival
and distant metastasis-free survival. Positive rate of NR2F2 protein tended to be
decreased with the progression of malignancy. Results of in vitro migration and
invasion assays suggested NR2F2's potential in inhibiting invasiveness. NR2F2 was
predicted to be negatively linked with EMT and TGF-beta-pathway related genes,
which was supported by observation of EMT-like morphology and changes in EMT
markers E-cadherin and Slug. Additionally, we found TGF-beta inhibited the
expression of NR2F2. GSEA also predicted that NR2F2 could be inversely associated
with chemoresistance, which was verified by results of in vitro growth inhibition
assays using chemotherapeutic agents. Our results demonstrated high NR2F2
transcript level was associated with favorable clinical outcome, which might be
due to NR2F2's inhibitory effect on TGF-beta-dependent EMT and its role in
inhibiting chemoresistance.
PMID- 25129344
TI - Ki67 measured in metastatic tissue and prognosis in patients with advanced breast
cancer.
AB - The purpose of this study is to determine the prognostic role of Ki67 evaluated
in relapse biopsies from patients with metastatic breast cancer (MBC). Two
hundred and ten patients diagnosed with MBC in Stockholm, Sweden between 1998 and
2009 and with Ki67 assessed at time of first systemic relapse (mKi67) were
retrospectively identified and divided into two groups according to mKi67
fraction (low <=20 %, high >20 %). Post-relapse survival was compared between the
groups using Kaplan-Meier and Cox regression methods. Death rate as function of
continuous mKi67 was also evaluated. Furthermore, the prognostic role of intra
individual change in Ki67 between primary tumor and matched metastasis was
explored by Kaplan-Meier plots. One hundred and twenty-five patients had low and
85 had high mKi67. Median survival was 25 and 17 months in low- and high-mKi67
group, respectively [hazard ratio (HR) 0.69, 95 % confidence intervals (CI) 0.51
0.92, P = 0.01]. In a multivariate model adjusted for prognostic confounders, low
mKi67 showed a non-significant trend toward better survival (HR 0.85, 95 %CI 0.62
1.16, P = 0.30). Nevertheless, mKi67 independently correlated with survival when
compared with primary tumor proliferation (HR 0.56, 95 %CI 0.38-0.81, P = 0.002).
The 2-year death rate steeply increased as mKi67 increased. Moreover, the change
from high in primary tumor to low in metastasis significantly correlated with
longer survival when compared with stable Ki67 levels (HR 0.48, 95 %CI 0.31-0.76,
P = 0.002). In this cohort of MBC patients, mKi67 inversely but not independently
correlated with survival. However, a significant association between mKi67 and
survival was shown regardless of primary tumor proliferation.
PMID- 25129345
TI - Pathologic complete response to neoadjuvant cisplatin in BRCA1-positive breast
cancer patients.
AB - The aim of this study is to estimate the frequency of pathologic complete
response (pCR) after neoadjuvant treatment with cisplatin chemotherapy in women
with breast cancer and a BRCA1 mutation. One hundred and seven women with breast
cancer and a BRCA1 mutation, who were diagnosed with stage I to III breast cancer
between December 2006 and June 2014, were treated with cisplatin 75 mg/m(2) every
3 weeks for four cycles, followed by mastectomy and conventional chemotherapy.
Information was collected on clinical stage, grade, hormone receptor status, and
Her2neu status prior to treatment. pCR was determined by review of surgical
specimens. One hundred and seven patients were enrolled in the study, including
93 patients who were treated for first primary breast cancer and 14 patients who
had previously received treatment for a prior cancer. A pCR was observed in 65 of
the 107 patients (61 %). Platinum-based chemotherapy is effective in a high
proportion of patients with BRCA1-associated breast cancer.
PMID- 25129347
TI - The failed first metatarsophalangeal joint implant arthroplasty.
AB - Chronic pain in a first metatarsophalangeal implant arthroplasty can be early or
late, and may be due to infection or implant failure. Although excisional
arthroplasty can be considered, the most predictable result will come from
arthrodesis. Conversion of a failed implant arthroplasty to fusion will usually
require structural bone graft, with slower healing times than primary fusion.
PMID- 25129346
TI - Abrogating phosphorylation of eIF4B is required for EGFR and mTOR inhibitor
synergy in triple-negative breast cancer.
AB - Triple-negative breast cancer (TNBC) patients suffer from a highly malignant and
aggressive disease. They have a high rate of relapse and often develop resistance
to standard chemotherapy. Many TNBCs have elevated epidermal growth factor
receptor (EGFR) but are resistant to EGFR inhibitors as monotherapy. In this
study, we sought to find a combination therapy that could sensitize TNBC to EGFR
inhibitors. Phospho-mass spectrometry was performed on the TNBC cell line, BT20,
treated with 0.5 MUM gefitinib. Immunoblotting measured protein levels and
phosphorylation. Colony formation and growth assays analyzed the treatment on
cell proliferation, while MTT assays determined the synergistic effect of
inhibitor combination. A Dual-Luciferase reporter gene plasmid measured
translation. All statistical analysis was done on CalucuSyn and GraphPad Prism
using ANOVAs. Phospho-proteomics identified the mTOR pathway to be of interest in
EGFR inhibitor resistance. In our studies, combining gefitinib and temsirolimus
decreased cell growth and survival in a synergistic manner. Our data identified
eIF4B, as a potentially key fragile point in EGFR and mTOR inhibitor synergy.
Decreased eIF4B phosphorylation correlated with drops in growth, viability,
clonogenic survival, and cap-dependent translation. Taken together, these data
suggest EGFR and mTOR inhibitors abrogate growth, viability, and survival via
disruption of eIF4B phosphorylation leading to decreased translation in TNBC cell
lines. Further, including an mTOR inhibitor along with an EGFR inhibitor in TNBC
with increased EGFR expression should be further explored. Additionally,
translational regulation may play an important role in regulating EGFR and mTOR
inhibitor synergy and warrant further investigation.
PMID- 25129348
TI - Pain after cheilectomy of the first metatarsophalangeal joint: diagnosis and
management.
AB - Cheilectomy is commonly performed for osteoarthritis of the first
metatarsophalangeal joint and generally has a successful outcome and high rate of
patient satisfaction over the short to medium term. Despite the relatively good
results achieved in most cases, a proportion of patients have ongoing pain after
cheilectomy. This article outlines the potential causes of ongoing pain,
including progression of osteoarthritis, neuralgic symptoms, and transfer
metatarsalgia. Management strategies for treating the ongoing symptoms are
discussed.
PMID- 25129349
TI - Deceptions in hallux valgus: what to look for to limit failures.
AB - The treatment of hallux valgus depends on multiple factors, including clinical
examination, patient considerations, clinical findings, radiographic assessment,
and surgeon preference. Appropriate procedure selection and proper technique will
usually result in good-to-excellent outcomes. Complications following hallux
valgus correction include recurrence, transfer metatarsalgia, avascular necrosis,
hallux varus, and nonunion and malunion of metatarsal osteotomies. In order to
decrease the risks of complication, a precise and meticulous physical examination
should be conducted preoperatively. In addition, a surgeon should select
appropriate osteotomies to correct complex hallux valgus deformities. As a
general principle, the severity of deformity dictates treatment options.
PMID- 25129350
TI - Iatrogenic hallux varus treatment algorithm.
AB - Iatrogenic hallux varus is a relatively rare complication of corrective hallux
valgus surgery that has multiple pathologic facets. It requires a comprehensive
assessment that focuses on joint flexibility, joint integrity, soft tissue
balance, and bony deformity. A step-wise treatment approach is used to address
all elements of the deformity. The literature on hallux varus treatments consists
mainly of retrospective case series, with several proposed procedures addressing
various degrees of deformity. Comparison of these procedures is a challenging
endeavor and each case should be considered on an individual basis.
PMID- 25129351
TI - Etiology and management of lesser toe metatarsophalangeal joint instability.
AB - The terms crossover toe and lesser metatarsophalangeal joint instability both
describe a deterioration of the soft tissue structures that give stability to the
lesser MTP joints. Initial treatment regimens focused on indirect repair of the
instability without addressing the primary pathology. A staging system of the
clinical examination and a grading system of the surgical findings are now
available to help surgeons classify and treat the plantar plate insufficiency.
Improved imaging techniques and direct surgical repair techniques through a
dorsal approach have changed the treatment and possibly the results of this
difficult condition.
PMID- 25129352
TI - Recurrent metatarsalgia.
AB - Recurrent metatarsalgia has a multifactorial etiology. The analysis of the cause
is critical in planning appropriate treatment. Understanding etiology helps
understand the mechanism of prevention, which is the best treatment. Recurrent
metatarsalgia is often due to poor technique or poor understanding of the
underlying problem. In hallux valgus surgery, recurrent metatarsalgia can be a
problem of position of the first metatarsal after an inappropriate or poorly done
first metatarsal osteotomy or a problem of gastrocnemius tightness not previously
recognized. The best treatment is to restore the normal anatomy but that is not
always possible, and surgery on affected rays could be the solution.
PMID- 25129353
TI - Problems associated with the excision of the hallux sesamoids.
AB - Disorders of the hallux sesamoids can be a source of considerable pain and
disability. Inappropriate or inept removal can lead to further disability and
pain. Surgical intervention should only follow careful accurate assessment,
appropriate investigation, and failure of conservative treatments.
PMID- 25129354
TI - The recurrent Morton neuroma: what now?
AB - Interdigital neuromas are a common cause of forefoot pain, and approximately 80%
of patients require surgical excision for symptom relief. Although 50% to 85% of
patients obtain relief after primary excision, symptoms may recur because of an
incorrect diagnosis, inadequate resection, or adherence of pressure on a nerve
stump neuroma. The symptom relief rate after reoperation is similar to that after
primary excision. A plantar longitudinal incision provides optimal exposure, and
transposition of the nerve stump into bone or muscle and avoids traction or
pressure on the nerve ending that can result in a painful stump neuroma.
Preoperative counseling is essential to align patient expectations with potential
outcomes.
PMID- 25129355
TI - Recurrent tarsal tunnel syndrome.
AB - Recurrence of tarsal tunnel syndrome after surgery may be due to inadequate
release, lack of understanding or appreciation of the actual anatomy involved,
variations in the anatomy of the nerve(s), failure to execute the release
properly, bleeding with subsequent scarring, damage to the nerve and branches,
persistent hypersensitivity of the nerves, and preexisting intrinsic damage to
the nerve. Approaches include more thorough release, use of barrier materials to
decrease adherence of the nerve to surrounding tissues to avoid traction
neuritis, excisions of neuromas using conduits, and consideration of nerve
stimulators and systemic medications to deal with persistent neural pain.
PMID- 25129356
TI - The midfoot is really deformed after hindfoot arthrodesis: how to salvage?
AB - Concomitant hindfoot and midfoot deformity is common. Hindfoot fusion is
associated with prolonged recovery and significant disability. Further surgery is
often required to obtain a plantigrade foot. Understanding normal structural and
kinematic relationships between the midfoot and hindfoot, as well as recognizing
common combined patterns of midfoot and hindfoot deformity, can minimize the
unanticipated consequences of hindfoot fusion. Treatment of residual or resultant
midfoot deformity requires a thorough analysis of the deformity and familiarity
with a variety of operative techniques for correction.
PMID- 25129357
TI - Triple arthrodesis: tips and tricks to navigate trouble.
AB - Triple arthrodesis is a powerful corrector of hindfoot deformity related to
trauma, rheumatoid arthritis, and long-standing peritalar subluxation with
posterior tibial tendon dysfunction. To avoid the common postoperative
complications related to triple arthrodesis, one must be meticulous in
preoperative evaluation as well as surgical technique. Presented are some tips
and tricks to avoid the common complications and provide the patient with a
plantigrade, stable foot, as well as some salvage options for triple arthrodesis
in a malunited position.
PMID- 25129358
TI - Nonunion of fifth metatarsal fractures.
AB - Metatarsal fractures are those most frequently encountered in the foot. More than
half of these are of the 5th metatarsal. The incidence is increasing, along with
the activity levels of the general population. Fractures of the 5th metatarsal
require careful evaluation and classification to ensure selection of the optimum
treatment plan. Distal fractures rarely require fixation, even when displacement
is wide. Cases of established nonunion or refracture require fixation.
PMID- 25129359
TI - The treatment of calcaneal malunion.
AB - The surgical treatment of calcaneal malunion is technically very demanding and
requires a careful assessment of the exact cause of the problem. A number of
different surgeries are available depending on the precise cause of symptoms. The
results are reasonable and justify surgery in an otherwise disabled group of
patients. Calcaneal malunion surgery should not be performed by the occasional
surgeon, as the price of error is usually amputation.
PMID- 25129360
TI - Ongoing pain and deformity after an excision of the accessory navicular.
AB - Although a painful accessory navicula and a pes planus often coexist, they are
not necessarily causally related, and each condition should be assessed and
treated individually. A child or adolescent will notice the rubbing of an
accessory navicula against footwear as the foot and boney swelling grows. The
cause of persistent local pain such as inadequate bony resection, scar pain,
irritation of the tibialis posterior tendon, and so forth should be sought and
addressed; management will depend on the specific presentation and previous
procedure performed. The cause of the ongoing pain should be investigated.
PMID- 25129361
TI - Taking out the tarsal coalition was easy: but now the foot is even flatter. What
now?
AB - Patients with a preexisting hindfoot deformity, who undergo resection (with or
without soft tissue interposition) of a tarsal coalition, may present with
recurrent pain and worsening planovalgus deformity. This is due to the secondary
effect of soft tissue contractures (lateral ligaments, peroneal tendons, calf
muscles) "pulling" the foot into more valgus. Physiotherapy and insoles may help
some patients. Depending on the flexibility of the hindfoot and the presence or
otherwise of joint degeneration, joint-preserving corrective procedures or
corrective joint fusions may be needed. Gastrocnemius, Achilles, and/or peroneal
tendon releases may be required, to avoid equinus or further recurrence.
PMID- 25129362
TI - Osteomyelitis of the foot and ankle: diagnosis, epidemiology, and treatment.
AB - Osteomyelitis of the foot and ankle is a common, potentially devastating
condition with diagnostic and treatment challenges. Understanding the
epidemiology and pathogenesis of osteomyelitis can raise clinical suspicion and
guide testing and treatments. History and physical examination, laboratory
studies, vascular studies, histologic and microbiologic analyses, and various
imaging modalities contribute to diagnosis and treatment. Treatment including
empiric broad-spectrum antibiotics and surgery should take a multidisciplinary
approach to optimize patient factors, ensure eradication of the infection, and
restore function. Optimization of vascular status, soft tissues, limb
biomechanics, and physiologic state of the patient must be considered to
accelerate and ensure healing.
PMID- 25129363
TI - Managing complications of foot and ankle surgery. Preface.
PMID- 25129364
TI - Retrospective comparison of nucleic acid sequence-based amplification, real-time
PCR, and galactomannan test for diagnosis of invasive aspergillosis.
AB - Invasive aspergillosis is a life-threatening infection in immunocompromised
patients, and treating these infections at an early stage is often crucial for a
favorable outcome. Early diagnosis, however, remains challenging. We performed a
retrospective comparison of three methods: real-time quantitative PCR (qPCR),
nucleic acid sequence-based amplification (NASBA), and galactomannan enzyme
linked immunosorbent assay (GM-ELISA); these detect circulating Aspergillus DNA,
RNA, and galactomannan, respectively. Blood samples from 80 patients at high risk
for invasive aspergillosis were tested by each assay. The sensitivity of NASBA,
qPCR, and GM-ELISA was 76.47% (95% CI, 58.4-88.6%), 67.65% (95% CI, 49.4-82.0%),
and 52.94% (95% CI, 35.4-69.8%), respectively, and the specificity was 80.43%
(95% CI, 65.6-90.1%), 89.13% (95% CI, 75.6-95.9%), and 80.43% (95% CI, 65.6
90.1%), respectively. We also evaluated the efficiency of the three tests in
various combinations. Perfect specificity (100%; 95% CI, 90.4-100%) and perfect
positive predictive value (100%; 95% CI, 77.1-100%) were achieved by combining
NASBA and qPCR testing in series. Testing with both NASBA and qPCR in parallel
was the most sensitive and had the highest Youden index. Our data support the
great potential of NASBA and qPCR, singly or in combination, for diagnosis of
invasive aspergillosis in high-risk populations.
PMID- 25129365
TI - Towards the targeted management of Chediak-Higashi syndrome.
AB - Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive congenital
immunodeficiency caused by mutations in CHS1, a gene encoding a putative
lysosomal trafficking protein. In the majority of patients, this disorder is
typically characterized by infantile-onset hemophagocytic lymphohistiocytosis
(HLH), which is lethal unless allogeneic transplantation is performed. A small
number of individuals have the attenuated form of the disease and do not benefit
from transplant. Improved outcomes of transplantation have been reported when
performed before the development of HLH, thus it is important to quickly
differentiate patients that present with the childhood form of disease and to
prematurely enroll them into a transplantation protocol. In addition, this would
also preclude those that exhibit clinical phenotypes of adolescent and adult CHS
from this treatment. Patients with an absence of cytotoxic T lymphocyte (CTL)
function have a high risk for developing HLH, and could therefore benefit the
most from early hematopoietic stem cell transplantation (HSCT). However, although
normal CTL cytotoxicity or bi-allelic missense mutations do not exclude the
occurrence of HLH in childhood, a more conservative approach is justified. This
article summarizes recent advances in the clinical characterization of CHS
patients, provides updates on promising new testing methods, and focuses on
specific therapeutic approaches.
PMID- 25129366
TI - Factors influencing Oncotype DX use in the management of early breast cancer: a
single centre experience.
AB - BACKGROUND: Oncotype DX recurrence score is a multi-gene assay which quantifies
the risk of distant recurrence in patients with hormone receptor-positive (HR+)
early breast cancer (EBC) treated with tamoxifen, and predicts the magnitude of
clinical benefit of adjuvant chemotherapy. This retrospective study examined
factors that were associated with use of Oncotype DX assay at a tertiary care
cancer centre in Ottawa, Canada. METHODS: One hundred consecutive patients (pts)
diagnosed with HR+, HER2/neu negative EBC (stage I-II), who underwent Oncotype DX
testing (Test Group) between 1st April 2010, and 30th June 2011 were included in
the study. A second cohort of 100 randomly selected patients with HR+, HER2/neu
negative EBC diagnosed from the same time period who did not receive Oncotype DX
testing were used as the control group (Control Group). Demographic and
clinicopathologic data were obtained from review of charts. Logistic regression
was performed to identify variables associated with Oncotype DX usage. FINDINGS:
Median age was 58 years (r: 26-77) in Test Group and 63 years (r: 30-81) in
Control Group. Sixty-two patients in the Test Group had T1 tumours, compared with
71 in the Control Group. The median 10-year recurrence risks from Adjuvant!
Online were 19% and 12% in the Test Group and Control Group, respectively.
Factors significantly associated with the utilisation of Oncotype DX assay on
multivariate analysis include age 50-64 (p=0.049), tumour size 10.1-20mm
(p=0.008) and grade 2 histological grade (p=0.004). INTERPRETATION: Usage of
Oncotype DX assay is associated with several clinicopathological factors. These
factors reflect the clinical uncertainty of benefit from chemotherapy in these
subpopulations of patients and suggest how Oncotype DX assay could complement
clinicopathological factors in helping clinicians on treatment selection.
PMID- 25129367
TI - Effectiveness of erlotinib treatment in advanced KRAS mutation-negative lung
adenocarcinoma patients: Results of a multicenter observational cohort study
(MOTIVATE).
AB - OBJECTIVES: Erlotinib is an epidermal growth factor receptor tyrosine-kinase
inhibitor (EGFR-TKI), used for the treatment of non-small cell lung cancer. As
the clinical significance of KRAS mutational status has not yet been clearly
determined in this setting, our aim was to investigate the efficacy of erlotinib
in advanced KRAS mutation-negative lung adenocarcinoma patients. MATERIALS AND
METHODS: MOTIVATE is an open-label, multicenter, observational trial with
Tarceva((r)) (erlotinib) monotherapy. Enrolled patients with advanced (stage
IIIB/IV) KRAS wild type (WT) lung adenocarcinoma refractory to one or two courses
of prior chemotherapy were treated with erlotinib at 150mg/day. The primary
endpoint was progression-free survival (PFS). Secondary endpoints were overall
survival (OS) and best tumor response rate (RR). RESULTS AND CONCLUSION: In
total, 327 patients were included. Median PFS and OS were 3.3 and 14.4 months,
respectively. Three patients (1.2%) had complete response, 51 patients (20.2%)
had partial response and 123 patients (48.8%) had SD. Significantly longer median
PFS and OS were observed in Eastern Oncology Cooperative Group Performance Status
(ECOG PS) 0-1 patients, as compared to ECOG PS 2-3 patients. The longest median
OS (20.5 months) was found in patients with ECOG PS 0-1 who received erlotinib as
a second-line therapy. There was no difference in median OS in cohorts stratified
to disease stage and smoking status. Female patients had both longer median PFS
and OS. Disease control rate was 70.2%. Our results suggest that erlotinib
represents a valid treatment option for patients with KRAS WT lung adenocarcinoma
and, moreover, that KRAS mutation analysis could help to identify clinically
relevant subgroups of NSCLC patients that may benefit from EGFR-TKI therapy.
PMID- 25129368
TI - Retrospective evaluation of thromboembolic events in patients with non-small cell
lung cancer treated with platinum-based chemotherapy.
AB - OBJECTIVES: Thromboembolic events (TE) are common in patients with cancer and are
potentially life-threatening. In lung cancer, little is known about thrombosis
during chemotherapy treatment. The aim of this study was to describe the
incidence of TE in patients with non-small cell lung cancer (NSCLC), occurring
during treatment with platinum-based chemotherapy. METHODS: We retrospectively
selected patients with NSCLC treated with platinum-based chemotherapy at the VU
University Medical Center Amsterdam between 2000 and 2012. Patients who underwent
recent surgery were excluded. All TE were included that occurred from start of
chemotherapy treatment until 30 days after last administration. RESULTS: Among
784 included patients, 63 (8.0%) patients had 69 TE during treatment. Forty-five
venous TE (VTE) and 24 arterial TE (ATE). Six patients had multiple events within
treatment period, 3 of which had simultaneous ATE and VTE. In total, 613 patients
were treated with cisplatin, 119 patients received carboplatin and 52 patients
received both in first- or second-line treatment. In 8% (55/665) of the patients
exposed to cisplatin a TE had occurred vs. 5% (8/171) in patients exposed to
carboplatin (p=0.42). The majority of TE occurred in the first 2 cycles (70%).
History of TE was related to occurrence of TE during chemotherapy (p<0.01).
Median PFS was similar in patients with and without TE (6.2 vs. 7.2 months,
respectively; p=0.10). Median OS was significantly shorter in patients with TE
(9.5 vs. 12.9 months, respectively; p=0.03). CONCLUSION: In our series, both ATE
and VTE were a common finding during chemotherapy. TE was a poor prognostic
factor. No difference in TE incidence was found between patients treated with
cisplatin or carboplatin.
PMID- 25129369
TI - Optimal mediastinal staging in non-small cell lung cancer: what is the role of
TEMLA and VAMLA?
AB - OBJECTIVES: The aim of this review is to present the current role of two
techniques of extensive mediastinal dissection, in the staging of lung cancer.
MATERIALS AND METHODS: The authors performed a search for original papers
published in English language, peer-reviewed journals. RESULTS: According to the
published evidence, definitions of VAMLA and TEMLA are given and the main
elements of the operative technique are briefly presented. Extensiveness and
completeness of mediastinal lymph node dissection using these techniques, their
diagnostic yield as well as complications and use of hospital resources are
discussed. The role of VAMLA and TEMLA in the contemporary staging of lung cancer
is presented in context of other staging techniques and the current clinical
practice guidelines. CONCLUSION: On the basis of the evidence currently
available, it may be concluded that VAMLA and TEMLA have no contemporarily use in
the routine mediastinal staging of lung cancer. This is because of their
invasiveness and - at least for TEMLA - high risk of complications and mortality,
which renders it unacceptable as a diagnostic procedure, and also due to the
development of equally accurate, but far less invasive techniques, i.e. EBUS-NA
and EUS-NA.
PMID- 25129371
TI - Maximum tumor diameter adjusted to the risk profile predicts biochemical
recurrence after radical prostatectomy.
AB - Currently, no consensus exists on the best method for tumor quantification in
prostate cancer (PCA), and its prognostic value remains controversial. We
evaluated how a newly defined maximum tumor diameter (MTD) might contribute to
the prediction of biochemical recurrence (BCR) in a consecutive series of PCA
patients treated with radical prostatectomy (RP). Patients with PCA who underwent
RP without neoadjuvant therapy at a single center were included for analysis. MTD
was defined as the largest diameter of all identified tumors in all three
dimensions (i.e., length, width, or depth) of the prostate ("Basel technique").
Cox regression models addressed the association of MTD with BCR in three risk
groups (low risk-prostate-specific antigen (PSA) < 10 ng/ml, pT2, and Gleason
score (GS) <= 6; intermediate risk-PSA >= 10 and <20 ng/ml and/or pT2 and GS = 7;
high risk-PSA > 20 ng/ml or pT3 or GS >= 8) and whole cohort. Within a median
follow-up of 44 months (interquartile range (IQR) 23-66), 48 patients (9.4 %) in
the intermediate-risk and high-risk groups experienced BCR. In multivariate Cox
regression analysis, PSA, pathological stage (pT stage), GS, positive surgical
margins (PSMs), and MTD > 19.5 mm were independent predictors for BCR (p < 0.05).
In subgroup analysis, MTD as a nominal variable (<24.5 and >24.5 mm) was the only
independent predictor of BCR in the intermediate-risk group (hazard ratio (HR)
9.933, 95 % confidence interval (CI) 2.070-47.665; p < 0.05). MTD is an
independent risk factor of BCR in PC patients after RP. The combination of the
MTD with other well-known prognostic factors after RP may improve decision-making
concerning follow-up intensity or adjuvant treatment.
PMID- 25129372
TI - Caudal extension graft versus columellar strut with plumping graft for acute
nasolabial angle correction in rhinoplasty surgery.
AB - Nasal tip support is an important factor to be considered in rhinoplasty surgery.
There are several techniques for improving tip support. Caudal extension graft
(CEG) and columellar strut with plumping graft (CSPG) are two methods in
rhinoplasty surgery. The final goal of this experimental study is to find the
most effective method for tip correction among patients with tip ptosis. In this
study, we compare two different methods which are used for the tip correction
among patients who suffer from acute nasolabial angle (NLA) and columellar
retraction. We performed a randomized clinical trial to compare correction ratio
of NLA and columellar show obtained via CEG and CSPG methods. Standardized
photographs were taken before the surgery and 12 months after the surgery to
compare results between two groups. The mean post-operation NLA was 112.55
degrees in CEG and 104.17 degrees in CSPG (p value < 0.001). Correction ratio
of NLA was 22.26 degrees in CEG and 13.77 degrees in CSPG (p value < 0.001).
The difference in the mean and the correction ratio of NLA were statistically
significant in two groups. The mean post-operation columellar show was 3.75 mm in
CEG and 3.44 mm in CSPG (p value < 0.083). The correction ratio of columellar
show was 1.76 mm in CEG and 1.20 mm in CSPG (p value < 0.007). The difference in
the correction ratio of the two groups was statistically significant. Our study
reveals that both techniques properly improve NLA and columellar show, however,
CEG is a more stable method in patients with tip ptosis.
PMID- 25129370
TI - A ThPOK-LRF transcriptional node maintains the integrity and effector potential
of post-thymic CD4+ T cells.
AB - The transcription factor ThPOK promotes CD4(+) T cell differentiation in the
thymus. Here, using a mouse strain that allows post-thymic gene deletion, we show
that ThPOK maintains CD4(+) T lineage integrity and couples effector
differentiation to environmental cues after antigenic stimulation. ThPOK
preserved the integrity and amplitude of effector responses and was required for
proper differentiation of types 1 and 2 helper T cells in vivo by restraining the
expression and function of Runx3, a nuclear factor crucial for cytotoxic T cell
differentiation. The transcription factor LRF acts redundantly with ThPOK to
prevent the transdifferentiation of mature CD4(+) T cells into CD8(+) T cells. As
such, the ThPOK-LRF transcriptional module was essential for CD4(+) T cell
integrity and responses.
PMID- 25129373
TI - Reply to the comment to the article "Open partial horizontal laryngectomies: a
proposal for classification by the working committee on nomenclature of the
European Laryngological Society".
PMID- 25129374
TI - Increased frequency of mitral valve prolapse in patients with deviated nasal
septum.
AB - Any abnormality of collagen may affect the tissues with higher collagen content,
e.g., joints, heart valves, and great arteries. Mitral valve prolapse (MVP) is a
characteristic of generalized collagen abnormality. Nasal septum (NS) is
constituted by osseous and cartilaginous septums that are highly rich in
collagen. We evaluated the co-existence of deviation of NS (DNS) in patients with
MVP. We retrospectively evaluated the recordings of echocardiographic and nasal
examinations of subjects with MVP and DNS. We analyzed the features of MVP and
anatomical classification of DNS among subjects. Totally, 74 patients with DNS
and 38 subjects with normal nasal passage were enrolled to the study. Presence of
MVP was significantly higher in patients with DNS compared to normal subjects (63
vs 26%, p < 0.001). Prolapse of anterior, posterior and both leaflets was higher
in patients with DNS. Thickness of anterior mitral leaflet was significantly
increased in patients with DNS (3.57 +/- 0.68 vs 4.59 +/- 1.1 mm, p < 0.001)
compared to normal subjects. Type I, II, and III, IV DNS were higher in frequency
in patients with MVP while type V and VI were higher in normal subjects. DNS is
highly co-existent with MVP and increased thickness of mitral anterior leaflet.
Generalized abnormality of collagen which is the main component of mitral valves
and nasal septum may be accounted for co-existence of MVP and DNS. Also co
existence of them may exaggerate the symptoms of patients with MVP due to limited
airflow through the nasal passage.
PMID- 25129375
TI - Inhibitory effect of naringin on microcystin-LR uptake in the freshwater snail
Sinotaia histrica.
AB - Gastropods are an important food source for aquatic animals, and have been
demonstrated to transfer microcystin (MC) to higher trophic levels through the
food web. In this study, we performed an oral administration experiment to
evaluate whether naringin can inhibit MC-LR uptake in the freshwater snail
Sinotaia histrica. We also observed the effect of MC-LR on the organizational
pathology of the hepatopancreas in S. histrica. Following exposure to cells of
Microcystis ichthyoblabe, S. histrica showed vacuolization and separation of the
basal lamina from cells in the hepatopancreas. Initial treatment with 1mM
naringin resulted in the prevention of MC-LR uptake rate by approximately 60%
over 8days, whereas initial treatment with 10mM naringin suppressed microcystin
uptake in 2days, despite an increase in MC-LR levels in the snail from days 5 to
8. With continuous treatment of 10mM naringin, the uptake prevention rate was
100%. Overall, we observed a strong inhibitory effect against MC-LR with naringin
treatment. This study provides a potential mechanism to prevent the uptake of
microcystin in the aquatic food web, thereby limiting its toxicity in
cyanobacterial bloom-polluted areas where the environment can be controlled and
may have further applications in the aquaculture of gastropods.
PMID- 25129376
TI - Trophectoderm DNA fingerprinting by quantitative real-time PCR successfully
distinguishes sibling human embryos.
AB - PURPOSE: To validate a novel and more practical system for trophectoderm DNA
fingerprinting which reliably distinguishes sibling embryos from each other.
METHODS: In this prospective and blinded study two-cell and 5-cell samples from
commercially available sibling cell lines and excess DNA from trophectoderm
biopsies of sibling human blastocysts were evaluated for accurate assignment of
relationship using qPCR-based allelic discrimination from 40 single nucleotide
polymorphisms (SNPs) with low allele frequency variation and high heterozygosity.
RESULTS: Cell samples with self relationships averaged 95.1 +/- 5.9 % similarity.
Sibling relationships averaged 57.2 +/- 5.9 % similarity for all 40 SNPs, and
40.8 +/- 8.2 % similarity for the 25 informative SNPs. Assignment of
relationships was accomplished with 100 % accuracy for cell lines and embryos.
CONCLUSIONS: These data demonstrate the first trophectoderm qPCR-based DNA
fingerprinting technology capable of unequivocal discrimination of sibling human
embryos. This methodology will empower research and development of new markers
of, and interventions that influence embryonic reproductive potential.
PMID- 25129378
TI - Lead isotope ratios for bullets, a descriptive approach for investigative
purposes and a new method for sampling of bullet lead.
AB - To establish a link between a bullet fired from a suspected firearm,
investigation of striation marks are one of the corner stones in the forensic
laboratory. Nevertheless, on some occasions, the bullet may be deformed to such
extent that traditional investigation of striation marks will be impossible.
Fragments of lead can be investigated by lead isotope ratio determination in
order to distinguish between bullets with different origin. This approach
initially seems reasonable, since the abundance of lead isotopes varies
significantly in nature. To make a method valid for forensic purposes, it is
important to have a fundamental understanding of the variation within a box of
lead bullets and the expected variation between boxes. Studies of variability
within and between boxes of ammunition are imperative to perform any type of
forensic interpretation, both in an investigative and evaluative context. This
work presents an extensive study of variability within and between boxes of
ammunition by use of multicollector inductive coupled mass spectrometry. As a
first approximation to classify bullets to any given source, a simple and robust
graphical method is presented. In addition, an easy-to-use sampling procedure of
lead is presented.
PMID- 25129379
TI - Ontological reconstruction of the clinical terminology of traditional Chinese
medicine.
AB - This study proposes the ontological reconstruction of the current clinical
terminology of traditional Chinese medicine (TCM). It also provides an overview
of preliminary work related to the said reconstruction, including the ontology
based analysis of TCM clinical terminology. We conclude that the ontological
reconstruction of TCM clinical terminology provides a proper translation from the
idealized organizational model to real-world implementation and to a formalized,
shared, and knowledge-based framework.
PMID- 25129377
TI - Pharmacologic overview of systemic chlorogenic acid therapy on experimental wound
healing.
AB - Chlorogenic acid (CGA) is a well-known natural antioxidant in human diet. To
understand the effects of CGA on wound healing by enhancing antioxidant defense
in the body, the present study sought to investigate the potential role of
systemic CGA therapy on wound healing and oxidative stress markers of the skin.
We also aimed to understand whether chronic CGA treatment has side effects on
pivotal organs or rat bone marrow during therapy. Full-thickness experimental
wounds were created on the backs of rats. CGA (25, 50, 100, 200 mg/kg) or vehicle
was administered intraperitoneally for 15 days. All rats were sacrificed on the
16th day. Biochemical, histopathological, and immunohistochemical examinations
were performed. Possible side effects were also investigated. The results
suggested that CGA accelerated wound healing in a dose-dependent manner. CGA
enhanced hydroxyproline content, decreased malondialdehyde and nitric oxide
levels. and elevated reduced glutathione, superoxide dismutase, and catalase
levels in wound tissues. Epithelialization, angiogenesis, fibroblast
proliferation, and collagen formation increased by CGA while polymorph nuclear
leukocytes infiltration decreased. CGA modulated matrix metalloproteinase-9 and
tissue inhibitor-2 expression in biopsies. Otherwise, high dose of CGA increased
lipid peroxidation of liver and kidney without affecting the heart and muscle
samples. Chronic CGA increased micronuclei formation and induced cytotoxicity in
the bone marrow. In conclusion, systemic CGA has beneficial effects in improving
wound repair. Antioxidant, free radical scavenger, angiogenesis, and anti
inflammatory effects of CGA may ameliorate wound healing. High dose of CGA may
induce side effects. In light of these observations, CGA supplementation or
dietary CGA may have benefit on wound healing.
PMID- 25129380
TI - Clinical data quality problems and countermeasure for real world study.
AB - Real world study (RWS) has become a hotspot for clinical research. Data quality
plays a vital role in research achievement and other clinical research fields. In
this paper, the common quality problems in the RWS of traditional Chinese
medicine are discussed, and a countermeasure is proposed.
PMID- 25129382
TI - Quantifying the sensitivity of ephemeral streams to land disturbance activities
in arid ecosystems at the watershed scale.
AB - Large areas of public lands administered by the Bureau of Land Management and
located in arid regions of the southwestern United States are being considered
for the development of utility-scale solar energy facilities. Land-disturbing
activities in these desert, alluvium-filled valleys have the potential to
adversely affect the hydrologic and ecologic functions of ephemeral streams.
Regulation and management of ephemeral streams typically falls under a spectrum
of federal, state, and local programs, but scientifically based guidelines for
protecting ephemeral streams with respect to land-development activities are
largely nonexistent. This study developed an assessment approach for quantifying
the sensitivity to land disturbance of ephemeral stream reaches located in
proposed solar energy zones (SEZs). The ephemeral stream assessment approach used
publicly-available geospatial data on hydrology, topography, surficial geology,
and soil characteristics, as well as high-resolution aerial imagery. These
datasets were used to inform a professional judgment-based score index of
potential land disturbance impacts on selected critical functions of ephemeral
streams, including flow and sediment conveyance, ecological habitat value, and
groundwater recharge. The total sensitivity scores (sum of scores for the
critical stream functions of flow and sediment conveyance, ecological habitats,
and groundwater recharge) were used to identify highly sensitive stream reaches
to inform decisions on developable areas in SEZs. Total sensitivity scores
typically reflected the scores of the individual stream functions; some
exceptions pertain to groundwater recharge and ecological habitats. The primary
limitations of this assessment approach were the lack of high-resolution
identification of ephemeral stream channels in the existing National Hydrography
Dataset, and the lack of mechanistic processes describing potential impacts on
ephemeral stream functions at the watershed scale. The primary strength of this
assessment approach is that it allows watershed-scale planning for low-impact
development in arid ecosystems; the qualitative scoring of potential impacts can
also be adjusted to accommodate new geospatial data, and to allow for expert and
stakeholder input into decisions regarding the identification and potential
avoidance of highly sensitive stream reaches.
PMID- 25129381
TI - Dioxin-induced thrombocyte aggregation in zebrafish.
AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a canonical member of a group of
dioxins which are byproducts of industrial combustion and are dangerous
environmental pollutants. TCDD has been shown to cause several abnormalities in
humans and wildlife, and recently, some dioxins have been found to activate
platelets. However, TCDD-mediated platelet activation pathways are elusive and
virtually nothing is known about TCDD activation of fish thrombocytes. To
investigate TCDD effect on thrombocyte function, we tested zebrafish blood in
presence of TCDD using a thrombocyte functional assay. We found that TCDD
activated thrombocytes. Further experiments showed that thrombocytes of fish
treated with TCDD formed both aggregates and filopodia. To investigate the
mechanism of TCDD-mediated activation of thrombocytes we used inhibitors for Gq,
cyclooxygenase-1, aryl hydrocarbon receptor (AHR), c-src, Akt, and ERK1/2. We
found that TCDD induces AHR which activates c-src and signals the activation of
Akt and ERK1/2 which are ultimately involved in generation of thromboxane A2.
Furthermore, we found that ADP potentiates TCDD action, which led to the
discovery that ADP itself activates AHR in the absence of TCDD. Taken together,
these results resolved the pathway of TCDD activation of thrombocytes and led to
the finding that ADP is an activator of AHR.
PMID- 25129383
TI - Nickel(II) biosorption from aqueous solutions by shrimp head biomass.
AB - The present study evaluates the capacity of shrimp (Farfantepenaeus aztecus) head
to remove toxic Ni(II) ions from aqueous solutions. Relevant parameters that
could affect the biosorption process, such as shrimp head pretreatment, solution
pH level, contact time and initial Ni(II) concentration, were studied in batch
systems. An increase in Ni(II) biosorption capacity and a reduction in the time
required to reach Ni(II) biosorption equilibrium was manifested by shrimp head
biomass pretreated by boiling in 0.5 N NaOH for 15 min; this biomass was
thereafter denominated APSH. The optimum biosorption level of Ni(II) ions onto
APSH was observed at pH 7.0. Biosorption increased significantly with rising
initial Ni(II) concentration. In terms of biosorption dynamics, the pseudo-second
order kinetic model described Ni(II) biosorption onto APSH best. The equilibrium
data adequately fitted the Langmuir isotherm model within the studied Ni(II) ion
concentration range. According to this isotherm model, the maximum Ni(II)
biosorption capacity of APSH was 104.22 mg/g. Results indicate that APSH could be
used as a low-cost, environmentally friendly, and promising biosorbent with high
biosorption capacity to remove Ni(II) from aqueous solutions.
PMID- 25129384
TI - Detection of a pneumonia virus of mice (PVM) in an African hedgehog (Atelerix
arbiventris) with suspected wobbly hedgehog syndrome (WHS).
AB - A pneumonia virus of mice (PVM) from an African hedgehog (Atelerix arbiventris)
with suspected wobbly hedgehog syndrome (WHS) was detected and genetically
characterized. The affected hedgehog had a nonsuppurative encephalitis with
vacuolization of the white matter, and the brain samples yielded RNA reads highly
homogeneous to PVM strain 15 (96.5% of full genomic sequence homology by analysis
of next generation sequencing). PVM antigen was also detected in the brain and
the lungs immunohistochemically. A PVM was strongly suggested as a causative
agent of encephalitis of a hedgehog with suspected WHS. This is a first report of
PVM infection in hedgehogs.
PMID- 25129385
TI - Minimally invasive surgery with spotlight work channel system in the treatment of
lumbar disc herniation: a retrospective study of 21 cases.
AB - A group of lumbar discherniation cases was treated with posterior discectomy and
decompression with Spotlight working channel. We retrospectively studied these
patients. To study and analyze the clinical efficacy and technical features of
discectomy which is carried out with the Spotlight channel technology. The
development of the minimally invasive spine surgery technology promotes new
instruments and materials. For minimally invasive spine surgery in channel
technology, the newly launched Depuy(Spine) working channel-Spotlight, which is a
new generation of wide viewing angle, single-hole device for minimally invasive
spine operations, has good prospects for clinical application. From March 2011 to
March 2012, 21 patients who were diagnosed with lumbar disc herniation were
treated with posterior discectomy and decompression with Spotlight working
channel, then the lumbar and leg pain visual analogue scale (VAS) scores of
before and after surgery and that of the follow-ups and the Oswestry Disability
Index were analyzed. All patients were successfully operated, and also they
received follow-ups for more than 1 year. The postoperative lumbar and leg pain
VAS scores improved significantly compared with the preoperative ones (P < 0.05)
and can effectively maintain (P > 0.05). The three time points of lumbar pain VAS
were 7.80 +/- 0.49, 1.51 +/- 0.52 and 1.47 +/- 0.59. The leg pain VAS were 7.53
+/- 0.50, 1.58 +/- 0.58 and 1.49 +/- 0.67. During the follow-ups of the cases in
this group, no case of disc herniation relapsed. Patients were satisfied with
that. The Spotlight channel system is one of the surgical approaches to
"minimally invasive spine technology with direct vision". It has a good range of
surgical indications. It can be carried out flexibly and used widely, which means
it will be easier for the surgeons to master.
PMID- 25129386
TI - A review of cavernous malformations with trigeminal neuralgia.
AB - Cavernous malformation with trigeminal neuralgia is relatively rare; only 10
cases have been reported. In deciding treatment strategies, it is helpful to
classify cavernous malformation according to its origin, as follows: in the
Gasserian ganglion (Type G); between the cisternal and intra-axial portions of
the trigeminal nerve root (Type C); in the intra-axial trigeminal nerve root in
the pons (Type P); or in the spinal tract of the trigeminal nerve root (Type S).
A 62-year-old male presented with left trigeminal neuralgia (V2 area) and left
facial hypoesthesia. Imaging studies revealed a cerebellopontine angle mass
lesion with characteristics of a cavernous malformation and evidence of
hemorrhage. The lesion was completely removed via a left anterior transpetrosal
approach. The mass was attached to the trigeminal nerve root; it was located
between the cisternal and intra-axial portions of the nerve root, and feeding off
microvessels from the trigeminal nerve vascular plexus. Histological examination
confirmed a cavernous malformation. In this case, the cavernous malformation was
Type C. We review cases of cavernous malformation with trigeminal neuralgia and
discuss therapeutic strategies according to the area of origin.
PMID- 25129387
TI - The islands are different: human perceptions of game species in Hawaii.
AB - Hawaii's game animals are all non-native species, which provokes human-wildlife
conflict among stakeholders. The management of human-wildlife conflict in Hawaii
is further complicated by the discrete nature of island communities. Our goal was
to understand the desires and perceived values or impacts of game held by
residents of Hawaii regarding six game species [pigs (Sus scrofa), goats (Capra
hircus), mouflon (Ovis musimon), axis deer (Axis axis), turkeys (Melagris
gallopavo), and doves (Geopelia striata)]. We measured the desired abundance of
game on the six main Hawaiian Islands using the potential for conflict index and
identified explanatory variables for those desires via recursive partitioning. In
2011 we surveyed 5,407 residents (2,360 random residents and 3,047 pre-identified
stakeholders). Overall 54.5 and 27.6 % of the emailed and mailed surveys were
returned (n = 1,510). A non-respondent survey revealed that respondents and non
respondents had similar interest in wildlife, and a similar education level. The
desired abundance of game differed significantly among stakeholders, species, and
islands. The desired abundance scores were higher for axis deer, mouflon, and
turkeys compared to pigs, goats or doves. Enjoyment at seeing game and the
cultural value of game were widespread explanatory variables for desired
abundance. Models for Lanai emphasized the economic value of game, whereas models
for Maui identified the potential for game to contaminate soil and water. Models
for Oahu and Kauai revealed concern for human health and safety. Given our
findings we recommend managers design separate management plans for each island
taking into consideration the values of residents.
PMID- 25129388
TI - A novel surface-confined glucaminium-based ionic liquid stationary phase for
hydrophilic interaction/anion-exchange mixed-mode chromatography.
AB - Glucaminium-based ionic liquids are a new class of recently developed ionic
liquids and prepared by functionalizing the amine group of N-methyl-d-glucamine,
which renders them good hydrophilicity due to the presence of the glucose
structure and charged quaternary ammonium group. In the present study, a
glucaminium-based ionic liquid N,N-diallyl-N-methyl-d-glucaminium bromide was
synthesized and subsequently bonded to the surface of 3-mercaptopropyl modified
silica materials through "thiol-ene" click chemistry. The obtained stationary
phase was characterized by elemental analysis and infrared spectroscopy, and then
packed as a HPLC column. A mixture of five nucleosides was used to characterize
the separation performance of the obtained column under HILIC mode and the column
efficiency was determined with cytidine as the test solute, reaching
80,000plates/m. Then, the retention behavior was evaluated by investigating the
effect of various chromatographic factors on retention of different types of
solutes, and the results revealed that the developed surface-confined glucaminium
based ionic liquid stationary phase exhibited a hydrophilic interaction/anion
exchange mixed-mode retention mechanism. Finally, two mixtures of nucleotides and
flavonoids were separated on the glucaminium-based ionic liquid column,
respectively under hydrophilic interaction and hydrophilic interaction/anion
exchange mixed-mode chromatography. In conclusion, the multimodal retention
capabilities of the glucaminium-based ionic liquid column could offer a wider
range of retention behavior and flexible selectivity toward polar and hydrophilic
compounds.
PMID- 25129389
TI - Trace analysis of endocrine disrupting compounds in environmental water samples
by use of solid-phase extraction and gas chromatography with mass spectrometry
detection.
AB - A novel analytical method using a continuous solid-phase extraction system in
combination with gas chromatography-mass spectrometry for the simultaneous
separation and determination of endocrine disrupting compounds (EDCs) is
reported. The method was applied to major EDCs of various types including
parabens, alkylphenols, phenylphenols, bisphenol A and triclosan in water.
Samples were preconcentrated by using an automatic solid-phase extraction module
containing a sorbent column, and retained analytes eluted with acetonitrile for
derivatization with a mixture of N,O-bis(trimethylsilyl)trifluoroacetamide and
trimethylchlorosilane. A number of variables potentially influencing recovery of
the target compounds such as the type of SPE sorbent (Silica gel, Florisil, RP
C18, Amberlite XAD-2 and XAD-4, Oasis HLB and LiChrolut EN), eluent and
properties of the water including pH and ionic strength, were examined. LiChrolut
EN was found to be the most efficient sorbent for retaining the analytes, with
~100% efficiency. The ensuing method was validated with good analytical results
including low limits of detection (0.01-0.08ng/L for 100mL of sample) and good
linearity (r(2)>0.997) throughout the studied concentration ranges. The method
exhibited good accuracy (recoveries of 90-101%) and precision (relative standard
deviations less than 7%) in the determination of EDCs in drinking, river, pond,
well, swimming pool and waste water. Waste water samples were found to contain
the largest number and highest concentrations of analytes (3.2-390ng/L).
PMID- 25129390
TI - High performance characterization of triacylglycerols in milk and milk-related
samples by liquid chromatography and mass spectrometry.
AB - In this work, ultra high performance liquid chromatography was used for the
characterization of non polar lipids (triacylglycerols) in milk samples of
different origin, as well as milk-derivatives. For tackling such a task, three
core-shell type octadecylsilica columns were serially coupled, reaching a total
stationary phase length of 45cm, using acetonitrile-isopropanol gradient elution
allowing triacylglicerol separation according to increasing partition number. The
employment of an ion-trap-time-of-flight detection in conjunction with
atmospheric-pressure chemical ionization mass spectrometry was carried out to
positively identify a number of 243 different triacylglycerols containing up to
22 fatty acids, with 2-22 carbon atom alkyl chain length, and 0-3 double bonds.
This work reports an extensive characterization of the triacylglycerol fraction
in milk and milk-related samples of different sources.
PMID- 25129391
TI - Evaluation of stationary phases packed with superficially porous particles for
the analysis of pharmaceutical compounds using supercritical fluid
chromatography.
AB - Superficially porous particles (SPP), or core shell particles, which consist of a
non-porous silica core surrounded by a thin shell of porous silica, have gained
popularity as a solid support for chromatography over the last decade. In the
present study, five unbonded silica, one diol, and two ethylpyridine (2-ethyl and
4-ethyl) SPP columns were evaluated under SFC conditions using two mixtures, one
with 17 drug-like compounds and the other one with 7 drug-like basic compounds.
Three of the SPP phases, SunShellTM 2-ethylpyridine (2-EP), PoroshellTM HILIC,
and Ascentis((r)) Express HILIC, exhibited superior performances relative to the
others (reduced theoretical plate height (hmin) values of 1.9-2.5 for neutral
compounds). When accounting for both achievable plate count and permeability of
the support using kinetic plot evaluation, the CortecsTM HILIC 1.6MUm and
Ascentis((r)) Express HILIC 2.7MUm phases were found to be the best choices among
tested SPPs to reach efficiencies up to 30,000 plates in the minimum amount of
time. For desired efficiencies ranging from 30,000 to 60,000 plates, the
SunShellTM 2-EP 2.6MUm column clearly outperformed all other SPPs. With the
addition of a mobile phase additive such as 10mM ammonium formate, which was
required to elute the basic components with sharp peaks, the PoroshellTM HILIC,
SunShellTM Diol and SunShellTM 2-EP phases represent the most orthogonal SPP
columns with the highest peak capacities. This study demonstrates the obvious
benefits of using columns packed with SPP on current SFC instrumentation.
PMID- 25129392
TI - Identification of coding exon 3 duplication in the BMPR1A gene in a patient with
juvenile polyposis syndrome.
AB - Juvenile polyposis syndrome is an autosomal dominant inherited disorder
characterized by multiple juvenile polyps arising in the gastrointestinal tract
and an increased risk of gastrointestinal cancers, specifically colon cancer.
BMPR1A and SMAD4 germline mutations have been found in patients with juvenile
polyposis syndrome. We identified a BMPR1A mutation, which involves a duplication
of coding exon 3 (c.230+452_333+441dup1995), on multiple ligation dependent probe
amplification in a patient with juvenile polyposis syndrome. The mutation causes
a frameshift, producing a truncated protein (p.D112NfsX2). Therefore, the
mutation is believed to be pathogenic. We also identified a duplication
breakpoint in which Alu sequences are located. These results suggest that the
duplication event resulted from recombination between Alu sequences. To our
knowledge, partial duplication in the BMPR1A gene has not been reported
previously. This is the first case report to document coding exon 3 duplication
in the BMPR1A gene in a patient with juvenile polyposis syndrome.
PMID- 25129393
TI - Impact of implantable transvenous device lead location on severity of tricuspid
regurgitation.
AB - BACKGROUND: Implantable device leads can cause tricuspid regurgitation (TR) when
they interfere with leaflet motion. The aim of this study was to determine
whether lead-leaflet interference is associated with TR severity, independent of
other causative factors of functional TR. METHODS: A total of 100 patients who
underwent transthoracic two-dimensional and three-dimensional (3D)
echocardiography of the tricuspid valve before and after lead placement were
studied. Lead position was classified on 3D echocardiography as leaflet
interfering or noninterfering. TR severity was estimated by vena contracta (VC)
width. Logistic regression analysis was used to identify factors associated with
postdevice TR, including predevice VC width, right ventricular end-diastolic and
end-systolic areas, fractional area change, right atrial size, tricuspid annular
diameter, TR gradient, device lead age, and presence or absence of lead
interference. Odds ratios were used to describe the association with moderate (VC
width >= 0.5 cm) or severe (VC width >= 0.7 cm) TR, separately, using bivariate
and stepwise multivariate logistic regression analysis. RESULTS: Forty-five of
100 patients showed device lead tricuspid valve leaflet interference. The septal
leaflet was the most commonly affected (23 patients). On bivariate analysis,
preimplantation VC width, right atrial size, tricuspid annular diameter, and lead
leaflet interference were significantly associated with postdevice TR. On
multivariate analysis, preimplantation VC width and the presence of an
interfering lead were independently associated with postdevice TR. Furthermore,
the presence of an interfering lead was the only factor associated with TR
worsening, increasing the likelihood of developing moderate or severe TR by 15-
and 11-fold, respectively. CONCLUSION: Lead-leaflet interference as seen on 3D
echocardiography is associated with TR after device lead placement, suggesting
that 3D echocardiography should be used to assess for lead interference in
patients with significant TR.
PMID- 25129394
TI - Assessment of left ventricular volumes with echocardiography and cardiac magnetic
resonance imaging: real-life evaluation of standard versus new semiautomatic
methods.
AB - BACKGROUND: Routine quantitative assessment of left ventricular (LV) volumes with
echocardiography is hindered by time-consuming methods requiring a manual trace
of the LV cavity from two apical two-dimensional planes. Thus, the aim of this
study was to evaluate faster new semiautomatic echocardiographic methods that
could represent a feasible alternative for the assessment of LV volumes and
ejection fraction (EF) in clinical practice. METHODS: Two semiautomatic methods,
the automated EF (Auto-EF) for two-dimensional echocardiography and the 4D Auto
LVQ tool for three-dimensional echocardiography (3DE), were compared with the
biplane modified Simpson's method and cardiac magnetic resonance (CMR) imaging in
47 patients. To evaluate the accuracy of volumetry, additional in vitro
measurements using water-filled latex balloons were performed with both
modalities. RESULTS: Results of balloon volumetry by echocardiography and CMR
measurements were in good agreement with real balloon volumes. The mean LV EF was
45 +/- 11% by Auto-EF, 45 +/- 11% by 3DE, 48 +/- 11% by Simpson's method, and 54
+/- 12% by CMR. Linear regression and Bland-Altman analyses showed good
associations for semiautomatic methods with Simpson's method (Auto-EF, r = 0.85,
bias = 3%, limits of agreement [LOA] = 12%; 3DE, r = 0.79, bias = 3%, LOA = 14%),
as well as with CMR (Auto-EF, r = 0.74, bias = 9%, LOA = 17%; 3DE, r = 0.73, bias
= 9%, LOA = 17%). Intra- and interobserver variability were 6% and 12% with Auto
EF and 8% and 11% with 3DE, respectively. CONCLUSIONS: Good correlations between
semiautomatic echocardiographic parameters for assessment of LV volumes and EF
could be observed when compared with Simpson's method or CMR. However,
intertechnique agreement analysis of absolute LV volumes revealed considerable
differences, with significant underestimation of volumes and EF with respect to
CMR.
PMID- 25129395
TI - A randomized, blinded, controlled USA field study to assess the use of fluralaner
tablets in controlling canine flea infestations.
AB - BACKGROUND: The novel isoxazoline molecule fluralaner provides 12 weeks activity
against fleas and 8 to 12 weeks against tick infestations according to label
claims. METHODS: This blinded, multi-center study in client-owned dogs evaluated
the flea control provided by a single oral fluralaner treatment (25-56 mg/kg;
BravectoTM, Merck Animal Health) compared to a control group administered three
oral spinosad (30 - 60 mg/kg; Comfortis(r), Elanco) treatments at 4-week
intervals together with an amitraz collar (9%, Preventic(r), Virbac). Households
were randomized (3:1 ratio) to either fluralaner (224 dogs, 118 households) or
control (70 dogs, 39 households). Within households, one primary dog with at
least 10 live fleas at enrollment was randomly selected for whole body flea
counts every 4 weeks through Week 12; all dogs were followed for safety until
Week 12. Fluralaner dogs received two additional doses at Weeks 12 and 24 for
further safety and palatability observations through Week 26. RESULTS: Geometric
mean flea count reductions from baseline for the fluralaner group at Weeks 4, 8,
and 12 were 99.7%, 99.8%, and 99.8%, respectively; and 96.1%, 99.5%, and 99.6%
for the spinosad controls. Percentages of flea-free primary dogs at Weeks 4, 8,
and 12 were 91.1%, 95.4%, and 95.3% for the fluralaner group; and 44.7%, 88.2%,
and 84.4% for the controls; the differences were significant at Weeks 4 (P <
0.0001) and 12 (P = 0.0370). Improvements in veterinarian assessed flea allergy
dermatitis (FAD) were observed in both groups. Fluralaner tablets were accepted
free choice in over 90% of doses. The most common adverse event was vomiting,
occurring in 7.1% of the fluralaner group and 14.3% of the controls. No treatment
related serious adverse events were reported. CONCLUSIONS: A single treatment of
dogs with the palatable fluralaner flavored chewable tablet provides a safe and
effective option for 12 weeks of flea control at least equivalent to that of 3
sequential treatments with spinosad tablets. Linked to the high level of flea
control was a substantial alleviation of associated signs of FAD.
PMID- 25129396
TI - Factors associated with gastrostomy tube dependence after concurrent
chemoradiotherapy for hypopharyngeal cancer.
AB - PURPOSE: We aimed to identify tumor- and treatment-related factors predicting
gastrostomy tube dependence after concurrent chemoradiotherapy (CCRT) for
hypopharyngeal cancer. METHODS: We performed a retrospective review of all
patients with hypopharyngeal cancer treated with CCRT between 2002 and 2012
except for those with residual or recurrent disease at evaluation. The incidence
of gastrostomy tube dependence, defined as complete or almost complete dependence
on tube feeding, at 6 months after the completion of treatment was the endpoint.
A total of 75 patients were analyzed in this study. RESULTS: Twelve patients (16
%) showed gastrostomy tube dependence. Among tumor-related factors, the subsite
(posterior wall versus pyriform sinus plus postcricoid) was the most significant
factor correlated with gastrostomy tube dependence (p < 0.01 by multivariate
analysis). The T category of the primary tumor was also correlated with
gastrostomy tube dependence on univariate analysis (p < 0.01). Among treatment
related factors, the radiation dose was not associated with gastrostomy tube
dependence. On the other hand, gastrostomy tube dependence was also correlated
with the requirement of supportive nutrition with a nasogastric tube at the
beginning of and during treatment (both p < 0.01). CONCLUSION: Risk factors for
gastrostomy tube dependence after the completion of CCRT for hypopharyngeal
cancer were identified.
PMID- 25129397
TI - Exploring the views of parents regarding dietary habits of their young cancer
surviving children.
AB - PURPOSE: Adult survivors of childhood cancer have a poor dietary intake. These
habits may be manifesting themselves soon after treatment completion. This
qualitative study aimed to assess parental views regarding the dietary habits of
young child cancer survivors. METHODS: The parents/carers of 18 young child
cancer patients (YCCP) treated at Sydney Children's Hospital, Australia (<5 years
since treatment completion and <13 years of age), participated in this study.
Eighteen age- and sex-matched healthy controls were recruited from Sydney-based
community organizations. The interview schedule was semi-structured, and the
interview was conducted over the telephone. Interviews were conducted until
thematic saturation was reached. Coding and analysis was facilitated by
qualitative analysis software. RESULTS: Three main themes emerged regarding
parental perceptions of YCCP current intake as compared with their pre-diagnosis
eating habits: (1) decreased fruit and vegetable intake, (2) increased
consumption of "junk food," and (3) increased portion sizes. Parents also
described a continuation of poor eating habits that were established during their
cancer treatment. The eating habits of YCCP were substantively different to that
described by parents of the control group. CONCLUSION: This exploratory project
revealed parental concern regarding their child's dietary intake once the cancer
treatment had been completed. The varying habits of YCCP are likely
multifactorial and may be related to treatment-related side effects and food
habits established during the cancer treatment.
PMID- 25129399
TI - Handmade trileaflet valved stent graft for pulmonary valve implantation.
PMID- 25129398
TI - Have "new" methods in medical education reached German-speaking Central Europe: a
survey.
AB - BACKGROUND: Simulation-based-training (SBT) in the education of health
professionals is discussed as an effective alternative for knowledge and skills
enhancement as well as for the establishment of a secure learning environment,
for learners and patients. In the Anglo-American region, SBT and simulation and
training centers (STC) are numbered as standard for medical training. In German
speaking Central Europe, priority is still given to the establishment of SBT and
STC. The purpose of this study was (i) to survey the status quo relating to the
existence and facilities of simulation and training centers at medical
universities in German-speaking Central Europe and (ii) the evaluation of
training methods, especially in the area of emergency medicine skills. METHODS:
All public and private medical universities or medical faculties in Germany (36),
Austria (4) and German-speaking Switzerland (3) were interviewed. In the survey,
information regarding the existence and facilities of STCs and information with
regards to the use of SBT in the area of emergency medicine was requested. The
questions were partly posed in a closed-ended-, in an open-ended- and in a
multiple choice format (with the possibility of selecting more than one answer).
RESULTS: Of a total of 43 contacted medical universities/medical faculties, 40
ultimately participated in the survey. As decisive for the establishment of a STC
the potential to improve the clinical-practical training and the demand by
students were listed. Obligatory training in a STC during the first and sixth
academic year was confirmed only by 12 institutions, before the first invasive
procedure on patients by 17 institutions. 13 institutions confirmed the use of
the STC for the further training of physicians and care-staff. Training for the
acute care and emergency medicine skills in the field of pediatrics, for the most
part, occurs decentralized. CONCLUSIONS: New methods in medical training have
reached German-speaking Central Europe, but the simulation and training centers
vary in size, equipment or regarding their integration into the obligatory
curriculum as much as the number and variety of the offering to be trained
voluntarily or on an obligatory basis.
PMID- 25129400
TI - Targeting the parahippocampal area by auditory cortex stimulation in tinnitus.
AB - BACKGROUND: The final common pathway in tinnitus generation is considered to be
synchronized auditory oscillatory hyperactivity. Intracranial auditory cortex
stimulation (iACS) via implanted electrodes has been developed to treat severe
cases of intractable tinnitus targeting this final common pathway, in the hope of
being a panacea for tinnitus. However, not everybody responds to this treatment.
OBJECTIVE: The electrical brain activity and functional connectivity at rest
might determine who is going to respond or not to iACS and might shed light on
the pathophysiology of auditory phantom sound generation. METHOD: The resting
state electrical brain activity of 5 patients who responded and 5 patients who
did not respond to auditory cortex implantation are compared using source
localized spectral activity (Z-score of log transformed current density) and
lagged phase synchronization. RESULTS: sLORETA source localization reveals
significant differences between responders vs non-responders for beta3 in left
posterior parahippocampal, hippocampal and amygdala area extending into left
insula. Gamma band differences exist in the posterior parahippocampal areas and
BA10. Functional connectivity between the auditory cortex and the hippocampal
area is increased for beta2, delta and theta2 in responders, as well as between
the parahippocampal area and auditory cortex for beta3. CONCLUSION: The resting
state functional connectivity and activity between the auditory cortex and
parahippocampus might determine whether a tinnitus patient will respond to a
cortical implant. The auditory cortex may only be a functional entrance into a
larger parahippocampal based tinnitus network.
PMID- 25129401
TI - The effects of anodal stimulation of the left prefrontal cortex on sentence
production.
AB - BACKGROUND: Most studies in which Anodal Transcranial Direct Current Stimulation
(A-tDCS) has been used to improve language production have focused on single
words. Yet sentence production requires more than lexical retrieval. For example,
successful suppression of the past and careful planning of the future are two
critical requirements for producing a correct sentence. Can A-tDCS improves
those, and by extension, production at the sentence level? OBJECTIVE/HYPOTHESIS:
Given that many aspects of sentence production beyond word retrieval require
frontally-mediated operations, we hypothesized that A-tDCS to the left prefrontal
cortex should benefit various operation involved in producing sentences, two of
which, suppression of the past and planning of the future, were targeted in this
study. METHODS: We used a paradigm that elicited construction of sentences
through event description, but was structured enough to allow for between-subject
comparison, clear error identification, and implementation of experimental
manipulations to probe certain aspects of production. RESULTS: We showed that A
tDCS to the left PFC reliably decreased the number of incomplete and errorful
sentences. When the origin of this improvement was probed, we found that A-tDCS
significantly decreased errors due to premature commitment to the future word
(insufficient internal monitoring), and had a marginal effect on errors of
perseverations (insufficient suppression of the past). CONCLUSION: We conclude
that A-tDCS is a promising tool for improving production at the sentence level,
and that improvement can be expected when internal monitoring and control over
verbal responses is impaired, or for certain cases of perseveratory errors.
PMID- 25129402
TI - Endogenous cortical oscillations constrain neuromodulation by weak electric
fields.
AB - BACKGROUND: Transcranial alternating current stimulation (tACS) is a non-invasive
brain stimulation modality that may modulate cognition by enhancing endogenous
neocortical oscillations by application of sine-wave electric fields. Yet, the
role of endogenous network activity in enabling and shaping the effects of tACS
has remained unclear. OBJECTIVE: We combined optogenetic stimulation and
multichannel slice electrophysiology to elucidate how the effect of a weak sine
wave electric field depends on the ongoing cortical oscillatory activity. We
hypothesized that endogenous cortical oscillations constrain neuromodulation by
tACS. METHODS: We studied the effect of weak sine-wave electric fields on
oscillatory activity in mouse neocortical slices. Optogenetic control of the
network activity enabled the generation of in vivo-like cortical oscillations for
studying the temporal relationship between network activity and sine-wave
electric field stimulation. RESULTS: Weak electric fields enhanced endogenous
oscillations but failed to induce a frequency shift of the ongoing oscillation
for stimulation frequencies that were not matched to the endogenous oscillation.
This constraint on the effect of electric field stimulation imposed by endogenous
network dynamics was limited to the case of weak electric fields targeting in
vivo-like network dynamics. Together, these results suggest that the key
mechanism of tACS may be enhancing, but not overriding, intrinsic network
dynamics. CONCLUSION: Our results contribute to understanding the inconsistent
tACS results from human studies and propose that stimulation precisely adjusted
in frequency to the endogenous oscillations is key to rational design of non
invasive brain stimulation paradigms.
PMID- 25129403
TI - Elevated levels of Th17 cells and Th17-related cytokines are associated with
disease activity in patients with inflammatory bowel disease.
AB - OBJECTIVE: Interleukin-17(IL-17)-producing T helper(Th)17 cells are considered as
a new subset of cells critical to the development of inflammatory bowel disease
(IBD). We aimed to investigate the distribution of Th17 cells, the expressions of
Th17-related cytokines (IL-17, IL-21 and IL-22) and their association with
disease activity in IBD patients. METHODS: We collected intestinal tissue
biopsies from 40 patients with active ulcerative colitis (UC), 20 patients with
active Crohn's disease (CD) and 20 healthy controls. The distribution of Th17
cells and expressions of Th17-related cytokines in colonic tissues were evaluated
by a standard immunohistochemical procedure. Serum IL-17, IL-21 and IL-22 levels
were determined by ELISA. Pearson's and Spearman's correlation analyses were
performed to analyze the correlation between the number of Th17 cells, the
expressions of Th17-related cytokines and disease activity index, endoscopic and
histological grading, and CRP and PLT levels, respectively. RESULTS: Compared
with healthy controls, the number of Th17 cells and the expressions of IL-17, IL
21 and IL-22 were significantly increased in active IBD patients (P < 0.05). In
addition, Pearson's and Spearman's correlation analyses showed that the number of
Th17 cells and the expressions of Th17-related cytokines were correlated with
disease activity index, endoscopic and histological grading, CRP and PLT levels
(P < 0.05). CONCLUSIONS: Th17 cells and Th17-related cytokines (IL-17, IL-21 and
IL-22) were increased in the intestinal mucosa in active IBD patients and may
play an important role in disease activity and mucosal damage.
PMID- 25129404
TI - A novel method for passing cerebrospinal fluid shunt tubing: a proof of principle
study.
AB - INTRODUCTION: Few innovations in the method of tunneling shunt tubing for
cerebrospinal fluid (CSF) shunt diversion have been made since this treatment of
hydrocephalus was first developed. Therefore, this feasibility study was
performed with the hope of identifying an improved technique that could
potentially carry fewer complications. MATERIALS AND METHODS: On 10 cadaver sides
and when placed in the supine position, small skin incisions were made at the
clavicle and ipsilateral subcostal region, and magnets were used to pass standard
shunt tubing between the two incisions. RESULTS: Nickel-plated magnets were less
effective in pulling the shunt tubing below the skin compared with ceramic
magnets. Of these, magnets with pull strengths of 150-200 lbs were the most
effective in dragging the subcutaneous tubing between the two incisions. No
obvious damage to the skin from the overlying magnet was seen in any specimen.
CONCLUSIONS: Few options exist for tunneling distal shunt tubing for CSF shunt
procedures. Future patient studies are needed to determine if the technique
described herein is superior to current methods, particularly when examining
patient groups that are at a greater risk for injury during tunneling shunt
catheters.
PMID- 25129405
TI - A trimodality comparison of volumetric bone imaging technologies. Part I: Short
term precision and validity.
AB - In vivo peripheral quantitative computed tomography (pQCT) and peripheral
magnetic resonance imaging (pMRI) modalities can measure apparent bone
microstructure at resolutions 200 MUm or higher. However, validity and in vivo
test-retest reproducibility of apparent bone microstructure have yet to be
determined on 1.0 T pMRI (196 MUm) and pQCT (200 MUm). This study examined 67
women with a mean age of 74+/-9 yr and body mass index of 27.65+/-5.74 kg/m2,
demonstrating validity for trabecular separation from pMRI, cortical thickness,
and bone volume fraction from pQCT images compared with high-resolution pQCT (hr
pQCT), with slopes close to unity. However, because of partial volume effects,
cortical and trabecular thickness of bone derived from pMRI and pQCT images
matched hr-pQCT more only when values were small. Short-term reproducibility of
bone outcomes was highest for bone volume fraction (BV/TV) and densitometric
variables and lowest for trabecular outcomes measuring microstructure.
Measurements at the tibia for pQCT images were more precise than at the radius.
In part I of this 3-part series focused on trimodality comparisons of precision
and validity, it is shown that pQCT images can yield valid and reproducible
apparent bone structural outcomes, but because of longer scan time and potential
for more motion, the pMRI protocol examined here remains limited in achieving
reliable values.
PMID- 25129406
TI - A Trimodality Comparison of Volumetric Bone Imaging Technologies. Part II: 1-Yr
Change, Long-Term Precision, and Least Significant Change.
AB - The previous article in this 3-part series demonstrated short-term precision and
validity for volumetric bone outcome quantification using in vivo peripheral (p)
quantitative computed tomography (pQCT) and magnetic resonance imaging (MRI)
modalities at resolutions 200 MUm or higher. However, 1-yr precision error and
clinically significant references are yet to be reported for these modalities.
This study examined 59 women with mean age of 75 +/- 9 yr and body mass index of
26.84 +/- 4.77 kg/m2, demonstrating the lowest 1-yr precision error, standard
errors of the estimate, and least significant change values for high-resolution
(hr) pQCT followed by pQCT, and 1.0-T pMRI for all volumetric bone outcomes
except trabecular number. Like short-term precision, 1-yr statistics for
trabecular separation were similar across modalities. Excluding individuals with
a previous history of fragility fractures, or who were current users of
antiresorptives reduced 1-yr change for bone outcomes derived from pQCT and pMR
images, but not hr-pQCT images. In Part II of this 3-part series focused on
trimodality comparisons of 1-yr changes, hr-pQCT was recommended to be the prime
candidate for quantifying change where smaller effect sizes are expected, but
pQCT was identified as a feasible alternative for studies expecting larger
changes.
PMID- 25129408
TI - UPLC-MS/MS determination of thiamphenicol in human plasma and its application to
a pharmacokinetic study.
AB - A sensitive and rapid ultra performance liquid chromatography-tandem mass
spectrometry (UPLC-MS/MS) method was developed to determine thiamphenicol (TAP)
in human plasma using chlorzoxazone as the internal standard (IS). Sample
preparation was accomplished through a liquid-liquid extraction procedure with
ethyl acetate to precipitation of plasma protein, and to a 0.1 mL plasma sample.
The analyte and IS were separated on an Acquity UPLC BEH C18 column (2.1 mm * 50
mm, 1.7 MUm) with the mobile phase of acetonitrile and 1% formic acid in water
with gradient elution at a flow rate of 0.40 mL/min. The detection was performed
on a triple quadrupole tandem mass spectrometer equipped with electrospray
ionization (ESI) by multiple reactions monitoring (MRM) of the transitions at m/z
354.3->185.1 for TAP and m/z 168.1->132.1 for IS. The linearity of this method
was found to be within the concentration range of 10-8000 ng/mL with a lower
limit of quantification of 10 ng/mL. Only 1.5 min was needed for an analytical
run. The method herein described was superior to previous methods and was
successfully applied to the pharmacokinetic study of TAP in healthy Chinese
volunteers after oral administration.
PMID- 25129407
TI - A Trimodality Comparison of Volumetric Bone Imaging Technologies. Part III: SD,
SEE, LSC Association With Fragility Fractures.
AB - Part II of this 3-part series demonstrated 1-yr precision, standard error of the
estimate, and 1-yr least significant change for volumetric bone outcomes
determined using peripheral (p) quantitative computed tomography (QCT) and
peripheral magnetic resonance imaging (pMRI) modalities in vivo. However, no
clinically relevant outcomes have been linked to these measures of change. This
study examined 97 women with mean age of 75 +/- 9 yr and body mass index of 26.84
+/- 4.77 kg/m(2), demonstrating a lack of association between fragility fractures
and standard deviation, least significant change and standard error of the
estimate-based unit differences in volumetric bone outcomes derived from both
pMRI and pQCT. Only cortical volumetric bone mineral density and cortical
thickness derived from high-resolution pQCT images were associated with an
increased odds for fractures. The same measures obtained by pQCT erred toward
significance. Despite the smaller 1-yr and short-term precision error for
measures at the tibia vs the radius, the associations with fractures observed at
the radius were larger than at the tibia for high-resolution pQCT. Unit
differences in cortical thickness and cortical volumetric bone mineral density
able to yield a 50% increase in odds for fractures were quantified here and
suggested as a reference for future power computations.
PMID- 25129409
TI - Simultaneous determination of N(1)-methylnicotinamide, L-carnitine, and
creatinine in human plasma and urine by liquid chromatography with mass
spectrometry for assessing the activities of multiple renal cationic
transporters.
AB - Organic cation transporters are responsible for the disposition of various
endogenous and therapeutic agents in humans; thus, there is a great need for the
development of a simple assay for simultaneous assessment of the activities of
multiple transporters. Using liquid chromatography-mass spectrometry (LC/MS), we
developed an assay that allows for simultaneous quantitation of plasma and
urinary levels of N(1)-methylnicotinamide (a substrate of hOCT2/hMATEs), L
carnitine (a substrate of hOCTN2), and creatinine (an indicator of glomerular
filtration). Samples were diluted with ultrapure water, deproteinized with
trichloroacetic acid, filtered, and then injected on a cation exchange column.
The analytes were separated with a gradient LC technique and detected by MS. The
total assay time was less than 8 min. The lower detection limits for N(1)
methylnicotinamide, L-carnitine, and creatinine were 2, 10, and 24 ng/mL,
respectively. Recovery of the analytes was almost complete. A preliminary
clinical study conducted in 25 healthy subjects revealed that the mean+/-SD for
the renal clearance (CLR) of N(1)-methylnicotinamide (272.7+/-81.0 mL/min) far
exceeded the glomerular filtration rate (116.3+/-19.6 mL/min), indicating the
involvement of active tubular secretion, while the mean CLR of clearance of L
carnitine was close to nil (1.5+/-1.4 mL/min), indicating almost complete tubular
reabsorption. The present method is potentially useful for clinical studies on
the genetic control of cationic transporter activities and the transporter
mediated drug interactions.
PMID- 25129410
TI - Simultaneous multi-component quantitation of Chinese herbal injection Yin-zhi
huang in rat plasma by using a single-tube extraction procedure for mass
spectrometry-based pharmacokinetic measurement.
AB - Ying-zhi-huang injection (YZH-I) is an injectable multi-herbal prescription
derived from the ancient Chinese remedy "Yin-chen-hao-tang", which is widely used
in the clinic for the treatment of jaundice and chronic liver diseases. To date,
little information is available on the pharmacokinetic properties of this poly
herbal formulation. Herein, we reported a simple, rapid and sensitive liquid
chromatography-tandem mass spectrometry (LC-MS/MS) method for quantitative
multiple reaction monitoring (MRM) of eight major ingredients of YZH-I (including
baicalin, baicalein, wogonoside, geniposide, geniposidic acid, chlorogenic acid,
neochlorogenic acid, and caffeic acid) in rat plasma. A fast single-tube multi
impurity precipitation extraction ("SMIPE") procedure was introduced for
straightforward plasma preparation, based on one-pot deproteinization
precipitation with acidified methanol extraction and in-situ multifunction
impurity removal by a solid sorbent mixture (anh. magnesium sulfate plus
octadecylsilane). Particularly, the addition of ascorbic acid in methanol (10
mg/mL) was found to exhibit a pronounced protective effect and significantly
increase extraction effectiveness of the herbal phenolic components. Some
pretreatment variables (protein precipitating solvent, acidifying agent and
sorbent) were optimized with acceptable matrix effect (-18 to 7.7%), extraction
recovery (65-88%) and process efficiency (62-91%) for the SMIPE-based LC-MRM
multi-analyte quantitation using matrix-matched calibration (5-1000 ng/mL)
without using internal standard. Mean accuracies were obtained in the range of 83
114% at three different fortification levels, with intra- and inter-day
variations within 13%. This validated method was successfully applied to the
simultaneous measurement and pharmacokinetic investigation of the chemical
constituents in rats following an intravenous administration of YZH-I.
PMID- 25129411
TI - Simultaneous determination of seven bufadienolides in rat plasma after oral
administration of Shexiang Baoxin Pill by liquid chromatography-electrospray
ionization-tandem mass spectrometry: application to a pharmacokinetic study.
AB - A liquid chromatography-electrospray ionization-tandem mass spectrometry method
was described for the simultaneous determination of resibufogenin, bufalin,
gamabufotalin, telibufagin, arenobufagin, cinobufagin and bufotalin in rat
plasma. Plasma samples were pretreated by liquid-liquid extraction with ethyl
acetate. Chromatographic separation was carried out on an ACQUITY HSS T3 column
with gradient elution using mobile phase consisting of acetonitrile-0.1% formic
acid in water at a flow rate of 0.3 mL/min. All analytes showed good linearity
over a wide concentration range (r>0.99). The lower limit of quantification was
in the range of 0.5-10 ng/mL for seven bufadienolides. The mean recovery of the
analytes ranged from 94.36 to 104.18%. The intra- and inter-day precisions were
in the range of 1.74-13.78% and the accuracies were between 89.37 and 101.38%.
The validated method was successfully applied to a pharmacokinetic (PK) study of
the seven bufadienolides in rat plasma after oral administration of Shexiang
Baoxin Pill (SBP). The selected PK marker compounds with typical
efficacy/toxicity may provide a practical solution for marker compound selection
and dosage design for the therapeutic drug monitoring and PK study of SBP in its
clinical applications.
PMID- 25129412
TI - Chromatographic fingerprint analysis of metabolites in natural and artificial
agarwood using gas chromatography-mass spectrometry combined with chemometric
methods.
AB - Agarwood is a resinous material formed in wounded Aquilaria sinensis in China,
which is widely used as an effective traditional Chinese medicine (TCM). This
study is aimed to use gas chromatography-mass spectrometry combined with
chemometric methods to create reliable criteria for accurate identification of
natural agarwood and artificial agarwood, as well as for quality evaluation of
artificial agarwood. Natural agarwood and artificial agarwood (stimulated by
formic acid or formic acid plus fungal inoculation) were used as standards and
controls for the gas chromatography-mass spectrometry (GC-MS) and multivariate
analysis. The identification criteria developed were applied to commercial
agarwood. A reliable criteria including correlation coefficient of GC-MS
fingerprint of natural agarwood and 22 markers of metabolism in natural and
artificial agarwood was constructed. Compared with chemically stimulated agarwood
(formic acid) and in terms of the 22 markers, artificial agarwood obtained by
formic acid stimulation and fungal inoculation were much closer to natural
agarwood. The study demonstrates that the chemical components of artificial
agarwood obtained by comprehensive stimulated method (formic acid plus fungal
inoculation) are much closer to the natural agarwood than those obtained by
chemically stimulated method (formic acid), as times goes by. A reliable criteria
containing correlation coefficient of GC-MS fingerprint of natural agarwood and
22 metabolism markers can be used to evaluate the quality of the agarwood. As an
application case, three samples were identified as natural agarwood from the 25
commercial agarwood by using the evaluation method.
PMID- 25129413
TI - Enhanced metabolic and redox activity of vascular aquatic plant Lemna valdiviana
under polarization in Direct Photosynthetic Plant Fuel Cell.
AB - In this study, duckweed species Lemna valdiviana was investigated as a
photoautotrophycally grown biocatalyst in recently developed Direct
Photosynthetic Plant Fuel Cell. Stable current outputs, reaching maximum of 226+/
11 mA/m(2), were achieved during the operating period. The electricity production
is associated with electrons generated through the light-dependent reactions in
the chloroplasts as well as the respiratory processes in the mitochondria and
transferred to the anode via endogenous electron shuttle, synthesized by the
plants as a specific response to the polarization. In parallel, a considerable
increase in the content of proteins (47%) and reserve carbohydrates (44%) of
duckweeds grown under polarization conditions was established by means of
biochemical analyses. This, combined with the electricity generation, makes the
technology a feasible approach for the duckweed farming.
PMID- 25129414
TI - Pollution profiles and health risk assessment of VOCs emitted during e-waste
dismantling processes associated with different dismantling methods.
AB - Pollution profiles of typical volatile organic compounds (VOCs) emitted during
dismantling of various printed circuit board assemblies (PCBAs) of e-wastes using
different methods were comparatively investigated in the real e-waste dismantling
workshops in South China in April 2013. Similar pollution profiles and
concentrations of VOCs were observed between dismantling mobile phone and hard
disk PCBAs by using electric blowers and between dismantling television and power
supplier PCBAs using electric heating furnaces. Aromatic hydrocarbons (accounting
for >60% of the sum of VOCs) were the dominant group during using electric
blowers, while aromatic (accounting for >44% of the sum of VOCs) and halogenated
hydrocarbons (accounting for >48% of the sum of VOCs) were the two dominant
groups which contributed equally using electric heating furnaces. However, the
distribution profiles of VOCs emitted during dismantling of televisions, hard
disks and micro motors using rotary incinerators varied greatly, though aromatic
hydrocarbons were still the dominant group. The combustion of e-wastes led to the
most severe contamination of VOCs, with total VOCs (3.3*10(4) MUg m(-3)) using
rotary incinerators about 190, 180, 139, and 40 times higher than those using
mechanical cutting, electric soldering iron, electric blower, and electric
heating furnace, respectively. Both cancer and non-cancer risks existed for
workers due to exposure to on-site emitted VOCs in all workshops especially in
those using rotary incinerators according to the USEPA methodology, whereas only
cancer risks existed in rotary incinerator workshops according to the American
Conference of Industrial Hygienists methodology.
PMID- 25129415
TI - Influence of pharyngolaryngeal anomalies diagnosed through indirect laryngoscopy
in the prediction of difficult intubation.
AB - OBJECTIVE: To determine the pharyngolaryngeal anomalies not usually included in
the evaluation of difficult airway, in order to investigate the influence of
these anomalies in the prediction of difficult intubation. To do this, indirect
laryngoscopy with a 70 degrees rigid laryngoscope was performed on all patients
during the preoperative period. METHODS: This is an observational, prospective
study on 300 consecutive patients who were scheduled for endotracheal intubation
under general anesthesia. In addition to assessing the airway in the preoperative
period by demographic and clinical predictors of difficult airway, rigid indirect
laryngoscopy was performed to diagnose pharyngolaryngeal anomalies. Later, under
general anesthesia and direct laryngoscopy it was checked to see if there was
difficulty in intubating the larynx, and its association with all previous
variables was investigated. A logistic regression model for prediction purposes
was developed, and its power of discrimination was achieved by assessing the area
under the curve. RESULTS: During the examination by indirect laryngoscopy 46
anomalies were found, which were as follows: 31 abnormalities of the epiglottis
(22 omega epiglottis, 9 flaccid or hypertrophic epiglottis); 6 findings of
hypertrophic lingual tonsils, 3 cases of upper airway tumors, and 6 patients with
tongue disorders. Intubation difficulty was found in 14 cases (4.66%). The
regression model found, and its coefficients to develop it were:
f(x)=1.322+(2.173 thyromental distance <6.5 cm)+(1.813 omega epiglottis)
(1.310*cm opening mouth). Global power of discrimination was 0.83, with a 95%
confidence interval from 0.709 to 0.952). CONCLUSION: Indirect laryngoscopy
allowed pharyngolaryngeal anomalies to be diagnosed, including omega epiglottis,
which was one of the variables included in the logistic regression model.
PMID- 25129416
TI - Clinical decision rules and D-Dimer in venous thromboembolism: current
controversies and future research priorities.
AB - Venous thromboembolism (VTE) is a potentially lethal clinical condition that is
suspected in patients with common clinical complaints, in many and varied,
clinical care settings. Once VTE is diagnosed, optimal therapeutic management
(thrombolysis, IVC filters, type and duration of anticoagulants) and ideal
therapeutic management settings (outpatient, critical care) are also
controversial. Clinical prediction tools, including clinical decision rules and D
Dimer, have been developed, and some validated, to assist clinical decision
making along the diagnostic and therapeutic management paths for VTE. Despite
these developments, practice variation is high and there remain many
controversies in the use of the clinical prediction tools. In this narrative
review, we highlight challenges and controversies in VTE diagnostic and
therapeutic management with a focus on clinical decision rules and D-Dimer.
PMID- 25129417
TI - Communication in healthcare: lessons from diversity.
PMID- 25129418
TI - Origin of plant auxin biosynthesis.
AB - The recent finding of the tryptophan aminotransferase (TAA)/flavin monooxygenase
(YUC) pathway as the principal route of auxin production in plants provides an
opportunity to revisit the origin of plant auxin biosynthesis. Phylogenetic
analyses of the TAA and YUC gene families provide very little evidence for the
production of indole-3-acetic acid (IAA) in algae. Instead, horizontal gene
transfer of YUCs from bacteria to the ancestral land plant suggests that the
TAA/YUC pathway is a land plant innovation. In this Opinion article we postulate
that the origin of tryptophan-dependent IAA biosynthesis in land plants might
have evolved in response to interactions with microbes, particularly bacteria,
allowing plants to counteract bacterial activities and control their own auxin
signaling.
PMID- 25129419
TI - [Paraneoplastic sensory neuropathy associated with squamous cell carcinoma of the
larynx].
PMID- 25129420
TI - Metastatic hepatocellular carcinoma to parotid glands.
AB - PATIENT: Male, 66. FINAL DIAGNOSIS: Hepatocellular carcinoma. SYMPTOMS: Abdominal
distension * painful right facial swelling * weight loss. MEDICATION: -. CLINICAL
PROCEDURE: -. SPECIALTY: -. OBJECTIVE: Rare disease. BACKGROUND: Hepatocellular
carcinoma is a common cancer, but it rarely metastasizes to the salivary glands.
A review of the literature revealed only 5 reported cases of hepatocellular
carcinoma metastatic to parotid glands. We here report an additional case of this
rare association. CASE REPORT: A 66-year-old male with a background of type 2
diabetes mellitus and post-alcoholic decompensated liver cirrhosis presented with
a progressively enlarging painful right facial swelling for 2 months that was
eventually found to be due to hepatocellular carcinoma metastatic to the right
parotid gland. Fine needle aspiration from the right parotid showed sheets and
single malignant cells that were interpreted as carcinoma not otherwise specific.
However, biopsy showed metastatic hepatocellular carcinoma into the right parotid
gland. CONCLUSIONS: We report an additional case of the rare metastasis of
hepatocellular carcinoma to the parotid glands. It should therefore be considered
in a patient with decompensated liver cirrhosis presenting with a parotid
swelling. Furthermore, the present case demonstrates the importance of the tissue
biopsy for obtaining an accurate final diagnosis.
PMID- 25129421
TI - In vitro fungicidal photodynamic effect of hypericin on Trichophyton spp.
AB - Hypericin is a natural photosensitizer used in photodynamic therapy (PDT), which
has shown in vitro antifungal effect against Candida spp. The aim of this study
was to evaluate the in vitro fungicidal effect of hypericin-PDT on dermatophytes.
Trichophyton rubrum and Trichophyton mentagrophytes strains were incubated with
different concentrations of hypericin for different times and exposed to light
emitting diode lamp (602 +/- 10 nm, 10.3 mW cm(-2), and fluence 37 J cm(-2)).
Using the optimal incubation time, 60 min, a 3-log fungicidal effect was achieved
with hypericin concentration ranges of 10-20 MUM for T. rubrum and 20-50 MUM for
T. mentagrophytes (p = 0.95). Confocal fluorescence microscopy showed the
localization of hypericin inside the dermatophytes diffusely distributed in the
cytoplasm of conidia and hyphae and outside the nucleus. In conclusion, hypericin
PDT has a fungicidal effect in vitro on dermatophytes. Hypericin seems to be a
promising photosensitizer to treat localized dermatophytic infections such as
tinea pedis and onychomycosis.
PMID- 25129422
TI - Magnetic resonance enterography in pregnant women with Crohn's disease: case
series and literature review.
AB - BACKGROUND: Evaluation of pregnant women with known or suspected Crohn's disease
(CD) remains a challenge. Magnetic Resonance Enterography (MRE) is a promising
diagnostic tool in these patients; however, the clinical data on MRE utilization
in pregnancy is scarce. The aim of the study was to describe the experience with
MRE in pregnant CD patients in a tertiary referral center. METHODS: We
retrospectively reviewed MRE studies performed in pregnant women with known or
suspected CD that were performed between January 2007 and November 2012. Imaging
findings, clinical management and outcome were extracted from patient's file and
electronic records. Image quality was evaluated. RESULTS: Ten studies of 9
patients were included. MRE protocol was modified to maximize maternal and fetal
safety, and intravenous gadolinium was not used. In 7 patients, CD diagnosis was
previously established; six were admitted with clinical symptoms consistent with
CD exacerbation, and an additional patient with a recurrent groin abscess without
apparent luminal symptoms. In all seven patients, imaging features consistent
with active CD were detected; new penetrating complications were detected in 4
patients. Two patients underwent MRE for suspected CD which was not comforted by
study results. The clinical management was significantly impacted by MRE results
in all positive cases. The image quality of the fast MRE sequences obtained
without gadolinium was satisfactory and allowed meaningful interpretation.
CONCLUSION: MRE with an adapted protocol for pregnancy is a reliable imaging
modality to manage in pregnant women with known or suspected CD.
PMID- 25129423
TI - The Postpartum Worry Scale-Revised: continuing validation with a sample of NICU
mothers.
AB - This study represents the second validation phase of the Postpartum Worry Scale
Revised (PWS-R). As the PWS-R includes items tapping infant health and
development concerns, we compare its psychometric properties with a sample of
NICU mothers and the online sample used in the initial validation. We conduct a
confirmatory factor analysis (CFA) to fit the latent factor structure previously
validated with the online sample to the NICU sample. We also examine the
reliability and construct validity of the PWS-R when used with a NICU sample. The
PWS-R's reliability remains good and moderate concurrent correlations with
theoretically similar constructs are shown with the newly created PWS-R factors.
Model testing with the NICU sample reveals a different three factor structure
than the four factor structure previously revealed with the online sample. The
psychometric findings for the PWS-R provide continuing support for its use as a
measure of postpartum worry; however, the differences in factor structure suggest
that the PWS-R scores of high risk samples such as NICU parents should not be
compared to those of community samples. Next steps in the iterative validation
process and recommendations for use are considered, particularly with regard to
high-risk samples.
PMID- 25129424
TI - Austenite layer and precipitation in high Co-Ni maraging steel.
AB - In high Co-Ni maraging steel, austenite has a great effect on the fracture
toughness of the steel and the precipitated carbides are the main strengthening
phase. In this study, both austenite layers and precipitation were observed and
their formation theory was analyzed by Thermo-Calc simulation and several
reported results. TEM and HRTEM observation results showed that the thickness of
the austenite layers was about 5-10 nm and the length of the needle-like
precipitated carbides was less than 10nm. The carbides maintained coherent or
semi-coherent relation with the matrix.
PMID- 25129425
TI - Looking forward to genetically edited fruit crops.
AB - The availability of genome sequences for many fruit crops has redefined the
boundaries of genetic engineering and genetically modified (GM) crop plants.
However commercialization of GM crops is hindered by numerous regulatory and
social hurdles. Here, we focus on recently developed genome-editing tools for
fruit crop improvement and their importance from the consumer perspective.
Challenges and opportunities for the deployment of new genome-editing tools for
fruit plants are also discussed.
PMID- 25129427
TI - There is hope in Pandora's box.
PMID- 25129426
TI - Effect of preinjury warfarin use on outcomes after head trauma in Medicare
beneficiaries.
AB - BACKGROUND: Elderly Americans are at increased risk of head trauma, particularly
fall related. The effect of warfarin on head trauma outcomes remains
controversial. METHODS: Medicare beneficiaries with head injuries from 2009 to
2011 were identified by International Classification of Diseases (ICD)-9 code.
Preinjury warfarin use was determined using Part D claims. Multiple logistic
regression models determined the association of preinjury warfarin on need for
hospitalization, intensive care unit care, and occurrence of intracranial
hemorrhage. Association between warfarin and in-hospital mortality was assessed
using a Cox proportional hazard model. RESULTS: Of 11,078 head injured patients,
5.2% were injured while on warfarin. Preinjury warfarin increased the odds of
intracranial hemorrhage by 40% and doubled the risk of 30-day in-hospital
mortality after adjusting for demographic and clinical factors. CONCLUSIONS:
Warfarin at the time of head injury increases the risk of adverse outcomes in
Medicare beneficiaries with head injuries. Caution should be used when initiating
anticoagulation in elderly Americans at risk for trauma.
PMID- 25129429
TI - Female military medical school graduates entering surgical internships: are we
keeping up with national trends?
AB - BACKGROUND: Ratios of women graduating from the only US military medical school
and entering surgical internships were reviewed and compared with national
trends. METHODS: Data were obtained from the Uniformed Services University of the
Health Sciences graduation announcements from 2002 to 2012. RESULTS: There were
1,771 graduates from 2002 to 2012, with 508 female (29%) and 1,263 male (71%)
graduates. Female graduates increased over time (21% to 39%; P = .014). Female
general surgery interns increased from 3.9% to 39% (P = .025). Female overall
surgical subspecialty interns increased from 20% in 2002 to 36% in 2012 (P =
.046). Women were represented well in obstetrics (57%), urology (44%), and
otolaryngology (31%), but not in neurosurgery, orthopedics, and ophthalmology (0%
to 20%). CONCLUSIONS: The sex disparity between military and civilian medical
students occurs before entry. Once in medical school, women are just as likely to
enter general surgery or surgical subspecialty as their male counterparts.
Increased ratio of women in the class is unlikely to lead to a shortfall except
in specific subspecialties.
PMID- 25129428
TI - Influence of adrenal pathology on perioperative outcomes: a multi-institutional
analysis.
AB - BACKGROUND: Endoscopic or open adrenalectomies are performed for variable
pathologies. We investigated if adrenal pathology affects perioperative outcomes
independent of operative approach. METHODS: A multi-institutional retrospective
review of 345 adrenalectomies was performed. A multivariate analysis was
utilized. RESULTS: Pathology groups included benign non-pheochromocytoma tumors
(50.4%), pheochromocytomas (41%), adrenocortical carcinomas (5.2%), and
metastatic tumors (3.4%). Controlling for age, body mass index, tumor size,
procedure type, and pathology, pheochromocytomas exhibited greater blood loss (92
mL more, P = .007) and operative times (33 min more, P < .001) than benign non
pheochromocytoma tumors. Metastatic tumors demonstrated longer operative times
(53 min more, P = .013). Open adrenalectomy was associated with greater blood
loss (396 mL more, P = .001), transfusion requirement (P = .021), operative times
(79 min more, P < .001), hospital stay (6.6 days more, P < .001) and
complications (P < .001) when compared with endoscopic adrenalectomy.
CONCLUSIONS: The type of adrenal pathology appears to influence blood loss and
operative time but not complications in patients undergoing adrenalectomy. Open
adrenalectomy remains a major driver of adverse perioperative outcomes.
PMID- 25129430
TI - Factors and outcomes associated with surgical treatment options of contralateral
breast cancer.
AB - BACKGROUND: The treatment for a contralateral breast cancer (CBC) presents a
growing dilemma given the expanding number of long-term survivors. We hypothesize
that there will be specific surgical treatment trends with demographic
differences between the treatment groups. METHODS: The Surveillance,
Epidemiology, and End Results (SEER) cancer database was queried to identify CBC
patients from 1998 to 2010. Relevant data were compared among the surgical
treatment groups of lumpectomy, mastectomy, and mastectomy/reconstruction.
RESULTS: Of 1,534 patients, 31% underwent lumpectomy and 69% underwent mastectomy
[201 (21%) mastectomy/reconstruction; 748 (69%) mastectomy alone]. Older patients
(age >80 years) were more likely to undergo lumpectomy; those with larger tumors
(T4) or node-positive disease more often underwent mastectomy. Overall survival
was significantly higher in the mastectomy/reconstruction group (P = .05).
CONCLUSIONS: Younger age, larger tumor size, and positive nodal disease were
independently associated with mastectomy. As the number of long-term breast
cancer survivors increases, factors contributing to CBC treatments must be
studied to maximize survival potential.
PMID- 25129431
TI - Malnutrition, sex ratio, and selection: a study based on the great leap forward
famine.
AB - This study tests the evolutionary hypothesis that maternal nutritional condition
can influence offspring sex ratio at birth in humans. Using the 1959-1961 Chinese
Great Leap Forward famine as a natural experiment, this study combines two large
scale national data sources and difference-in-differences method to identify the
effect of famine-induced acute malnutrition on sex ratio at birth. The results
show a significant famine-induced decrease in the proportion of male births in
the 1958, 1961, and 1964 in the urban population but not in the rural population.
Given that both the urban and rural populations suffered from the famine-induced
malnutrition, and that the rural population experienced a drastic famine-induced
mortality increase and fertility reduction, these results suggest the presence of
a short-term famine effect, a long-term famine effect, and a selection effect.
The timing of the estimated famine effects suggests that famine influences sex
ratio at birth by differential implantation and differential fetal loss by fetal
sex.
PMID- 25129432
TI - Psychomotor retardation is a scar of past depressive episodes, revealed by simple
cognitive tests.
AB - The cumulative duration of depressive episodes, and their repetition, has a
detrimental effect on depression recurrence rates and the chances of
antidepressant response, and even increases the risk of dementia, raising the
possibility that depressive episodes could be neurotoxic. Psychomotor retardation
could constitute a marker of this negative burden of past depressive episodes,
with conflicting findings according to the use of clinical versus cognitive
assessments. We assessed the role of the Retardation Depressive Scale (filled in
by the clinician) and the time required to perform the neurocognitive d2
attention test and the Trail Making Test (performed by patients) in a sample of
2048 depressed outpatients, before and after 6 to 8 weeks of treatment with
agomelatine. From this sample, 1140 patients performed the TMT-A and -B, and 508
performed the d2 test, at baseline and after treatment. At baseline, we found
that with more past depressive episodes patients had more severe clinical level
of psychomotor retardation, and that they needed more time to perform both d2 and
TMT. When the analyses were performed again after treatment, and especially when
the analyses were restricted to patients with clinical remission, the cognitive
tests were the only ones correlated with past depressive episodes. Psychomotor
retardation tested at a cognitive level was therefore systematically revealing
the burden of past depressive episodes, with an increased weight for patients
with less remaining symptoms. If prospectively confirmed, interventions such as
cognitive remediation therapy could benefit from a more specific focus on
neurocognitive retardation.
PMID- 25129433
TI - Porcine reproductive and respiratory syndrome virus infection triggers HMGB1
release to promote inflammatory cytokine production.
AB - The high mobility group box 1 (HMGB1) protein is an endogenous damage-associated
molecular pattern (DAMP) molecule involved in the pathogenesis of various
infectious agents. Based on meta-analysis of all publicly available microarray
datasets, HMGB1 has recently been proposed as the most significant immune
modulator during the porcine response to porcine reproductive and respiratory
syndrome virus (PRRSV) infection. However, the function of HMGB1 in PRRSV
pathogenesis is unclear. In this study, we found that PRRSV infection triggers
the translocation of HMGB1 from the nucleus to the extracellular milieu in MARC
145 cells and porcine alveolar macrophages. Although HMGB1 has no effect on PRRSV
replication, HMGB1 promotes PRRSV-induced NF-kappaB activation and subsequent
expression of inflammatory cytokines through receptors RAGE, TLR2 and TLR4. Our
findings show that HMGB1 release, triggered by PRRSV infection, enhances the
efficiency of virus-induced inflammatory responses, thereby providing new
insights into the pathogenesis of PRRSV infection.
PMID- 25129435
TI - Kilham Rat Virus-induced type 1 diabetes involves beta cell infection and intra
islet JAK-STAT activation prior to insulitis.
AB - We used the LEW1.WR1 rat model of Kilham Rat Virus (KRV)-induced type 1 diabetes
(T1D) to test the hypothesis that disease mechanisms are linked with beta cell
infection and intra-islet immune activation prior to insulitis. KRV induces genes
involved in type I and type II interferon pathways in islet cell lines in vitro
and in islets from day-5-infected animals in vivo via mechanisms that do not
involve insulitis, beta cell apoptosis, or impaired insulin expression.
Immunohistochemistry studies indicated that KRV protein is expressed in beta
cells 5 days following infection. KRV induces the phosphorylation of Janus Kinase
1/2 (JAK1/2) and signal transducer and activator of transcription 1 (STAT-1) in
islet cells via a mechanism that could involve TLR9 and NF-kappaB pathways. These
data demonstrate for the first time that KRV-induced islet destruction is
associated with beta cell infection and intra-islet innate immune upregulation
early in the disease process.
PMID- 25129434
TI - Regulation of human genome expression and RNA splicing by human papillomavirus 16
E2 protein.
AB - Human papillomavirus 16 (HPV16) is causative in human cancer. The E2 protein
regulates transcription from and replication of the viral genome; the role of E2
in regulating the host genome has been less well studied. We have expressed HPV16
E2 (E2) stably in U2OS cells; these cells tolerate E2 expression well and gene
expression analysis identified 74 genes showing differential expression specific
to E2. Analysis of published gene expression data sets during cervical cancer
progression identified 20 of the genes as being altered in a similar direction as
the E2 specific genes. In addition, E2 altered the splicing of many genes
implicated in cancer and cell motility. The E2 expressing cells showed no
alteration in cell growth but were altered in cell motility, consistent with the
E2 induced altered splicing predicted to affect this cellular function. The
results present a model system for investigating E2 regulation of the host
genome.
PMID- 25129437
TI - The Cucumber leaf spot virus p25 auxiliary replicase protein binds and modifies
the endoplasmic reticulum via N-terminal transmembrane domains.
AB - Cucumber leaf spot virus (CLSV) is a member of the Aureusvirus genus, family
Tombusviridae. The auxiliary replicase of Tombusvirids has been found to localize
to endoplasmic reticulum (ER), peroxisomes or mitochondria; however, localization
of the auxiliary replicase of aureusviruses has not been determined. We have
found that the auxiliary replicase of CLSV (p25) fused to GFP colocalizes with ER
and that three predicted transmembrane domains (TMDs) at the N-terminus of p25
are sufficient for targeting, although the second and third TMDs play the most
prominent roles. Confocal analysis of CLSV infected 16C plants shows that the ER
becomes modified including the formation of punctae at connections between ER
tubules and in association with the nucleus. Ultrastructural analysis shows that
the cytoplasm contains numerous vesicles which are also found between the
perinuclear ER and nuclear membrane. It is proposed that these vesicles
correspond to modified ER used as sites for CLSV replication.
PMID- 25129436
TI - Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits
virus-specific immune response in mice.
AB - Yellow fever (YF) causes an acute hemorrhagic fever disease in tropical Africa
and Latin America. To develop a novel experimental YF vaccine, we applied iDNA
infectious clone technology. The iDNA represents plasmid that encodes the full
length RNA genome of 17D vaccine downstream from a cytomegalovirus (CMV)
promoter. The vaccine was designed to transcribe the full-length viral RNA and to
launch 17D vaccine virus in vitro and in vivo. Transfection with 10 ng of iDNA
plasmid was sufficient to start replication of vaccine virus in vitro. Safety of
the parental 17D and iDNA-derived 17D viruses was confirmed in AG129 mice
deficient in receptors for IFN-alpha/beta/gamma. Finally, direct vaccination of
BALB/c mice with a single 20 MUg dose of iDNA plasmid resulted in seroconversion
and elicitation of virus-specific neutralizing antibodies in animals. We conclude
that iDNA immunization approach combines characteristics of DNA and attenuated
vaccines and represents a promising vaccination strategy for YF.
PMID- 25129438
TI - Removal of a small C-terminal region of JCV and SV40 large T antigens has
differential effects on transformation.
AB - The large T antigen (LT) protein of JCV and SV40 polyomaviruses is required to
induce tumors in rodents and transform cells in culture. When both LTs are
compared side-by-side in cell culture assays, SV40 shows a more robust
transformation phenotype even though the LT sequences are highly conserved. A
complete understanding of SV40's enhanced transforming capabilities relative to
JCV is lacking. When the least conserved region of the LT proteins, the variable
linker and host range region (VHR), was removed, changes in T antigen expression
and cellular p53 post-translational modifications occurred, but interaction with
the pRB pathway was unaffected. Transformation assessed by growth in low serum
was reduced after VHR truncation of the SV40, but not the JCV, T antigen.
Conversely, anchorage independent transformation was enhanced only by truncation
of the JCV VHR. This is the first report to link the SV40 or JCV VHR region to
transformation potential.
PMID- 25129439
TI - Relationship between IL-10 expression and prognosis in patients with primary
breast cancer.
AB - This retrospective study was designed to investigate the relationship between the
expression of IL-10, CD4, CD8, and FOXP3 and clinicopathological features and
prognosis in breast cancer patients. The expression of IL-10, CD4, CD8, and FOXP3
was detected by immunohistochemistry. Staining intensity of only IL-10 was
associated with disease-free survival and distance disease-free survival
(P<0.05). Staining density of IL-10 in stromal cells was associated with overall
survival and distance disease-free survival (P<0.05). IL-10 expression levels
might be used as a prognostic indicator for the recurrence, metastasis, and
survival of breast cancer patients.
PMID- 25129440
TI - Down-regulation of HDAC5 inhibits growth of human hepatocellular carcinoma by
induction of apoptosis and cell cycle arrest.
AB - Histone deacetylases (HDACs) play a critical role in the proliferation,
differentiation, and apoptosis of cancer cells. An obstacle for the application
of HDAC inhibitors as effective anti-cancer therapeutics is that our current
knowledge on the contributions of different HDACs in various cancer types remains
scarce. The present study reported that the mRNA and protein levels of HDAC5 were
up-regulated in human hepatocellular carcinoma (HCC) tissues and cells as shown
by quantitative real-time PCR and Western blot. MTT assay and BrdU incorporation
assay showed that the down-regulation of HDAC5 inhibited cell proliferation in
HepG2, Hep3B, and Huh7 cell lines. Data from in vivo xenograft tumorigenesis
model also demonstrated the anti-proliferative effect of HDAC5 depletion on tumor
cell growth. Furthermore, the suppression of HDAC5 promoted cell apoptosis and
induced G1-phase cell cycle arrest in HCC cells. On the molecular level, we
observed altered expression of apoptosis-related proteins such as p53, bax, bcl
2, cyto C, and caspase 3 in HDAC5-shRNA-transfected cells. Knockdown of HDAC5 led
to a significant up-regulation of p21 and down-regulation of cyclin D1 and
CDK2/4/6. We also found that the down-regulation of HDAC5 substantially increased
p53 stability and promoted its nuclear localization and transcriptional activity.
Our study suggested that knockdown of HDAC5 could inhibit cancer cell
proliferation by the induction of cell cycle arrest and apoptosis; thus,
suppression of HDAC5 may be a viable option for treating HCC patients.
PMID- 25129441
TI - Long non-coding RNA CARLo-5 is a negative prognostic factor and exhibits tumor
pro-oncogenic activity in non-small cell lung cancer.
AB - Despite recent advances in the management of non-small cell lung cancer (NSCLC),
the prognosis of NSCLC is still relatively poor. Thus, it is of great importance
to identify novel effective diagnostic and prognostic biomarker of NSCLC. A
growing volume of literature has demonstrated the vital roles of long non-coding
RNAs (lncRNAs) in cancer biology. Cancer-associated region long non-coding RNA
(CARLo-5), a recently identified lncRNA, was initially characterized in colon
cancer. However, little is known about its role in NSCLC. In the present study, a
great upregulation of CARLo-5 was observed in cancer tissues compared to their
adjacent normal tissues. Meanwhile, patients with high CARLo-5 expression have
significantly poorer prognosis than those with low expression. Inhibition of
CARLo-5 by siRNA suppressed the proliferation, migration, and invasion in NSCLC
cell lines in vitro. In addition, silencing of CARLo-5 reversed the epithelial
mesenchymal transition in NSCLC cell line. Our study suggests that CARLo-5 may
represent a prognostic marker and a potential therapeutic target of NSCLC.
PMID- 25129442
TI - Outcome of gemcitabine plus molecular targeted agent for treatment of pancreatic
cancer: a meta-analysis of prospective phase III studies.
AB - The aim of this study is to assess the clinical outcome of gemcitabine (GEM) plus
molecular targeted agents (MTAs) for treatment of pancreatic cancer, in the
purpose of providing fundamental data for clinical practice. Databases like
PubMed, EMBASE, and MEDLINE, EMBASE and Cochrane Library were searched to
retrieve phase III clinical randomized controlled trials related to GEM plus MTAs
for pancreatic cancer (up to Oct 2013). Literatures were independently screened
by two researchers according to the inclusion and exclusion criteria. Data were
extracted and analyzed by using Stata 11.0 software. Total, 11 studies were
included, involving 5,451 participants who were divided into GEM plus MTAs group
(n=2,729) and GEM plus placebo group (n=2,722). There was no significant
difference in overall survival, progression-free survival, response rate,
complete response, partial response, and clinical benefit rate between two
groups. Compared with GEM plus placebo group, stable disease of GEM plus MTAs
group was significantly increased (risk ratios (RRs) =1.14, 95% confidence
interval (CI) 1.04-1.21, P=0.003). Further subgroup analysis indicated that GEM
plus epidermal growth factor receptor (EGFR) inhibitor use induced higher
response rate and clinical benefit rate than GEM plus placebo group (RRs=1.19,
95% CI 1.09-1.31, P=0.000; RR=1.18, 95% CI 1.09-1.27, P=0.000). In addition, no
significant difference in 3-4 grade adverse reactions (incidence, anemia rate,
neutropenia rate, and thrombocytopenia rate) was identified between two groups.
GEM plus MTAs may be effective and safe for stabilizing patients suffering
advanced pancreatic cancer, especially EGFR inhibitor.
PMID- 25129443
TI - Evaluation of squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IGM)
and alpha-L-fucosidase (AFU) as novel diagnostic biomarkers for hepatocellular
carcinoma.
AB - Hepatocellular carcinoma (HCC) surveillance lacks a reliable biomarker. Alpha
fetoprotein (AFP) is the most widely used. However, not all HCCs secrete AFP. AFP
may be elevated with cirrhosis in the absence of HCC. Serum alpha-L-fucosidase
(AFU) and squamous cell carcinoma antigen-immunoglobulin M complex (SCCA-IgM)
were found to be useful markers in diagnosing HCC. SCCA-IgM and AFU were assessed
by ELISA technique; AFP was measured by enzyme chemiluminescence in serum of 40
patients with HCC, 30 patients with liver cirrhosis, and 20 healthy control
participants to compare their accuracy in early diagnosis of HCC. Serum SCCA-IgM
and AFU levels were significantly elevated in HCC group compared to cirrhotic
group (P value<0.001 and <0.001, respectively). Receiver operating characteristic
curve showed the optimal cutoff value for SCCA-IgM was 233 AU/ml with sensitivity
87.5% and specificity 66% and for AFU was 25 U/L with sensitivity 87.5% and
specificity 98%. AFP cutoff value was 48 ng/mL with sensitivity of 70% and
specificity of 53.3%. The simultaneous determination of AFP and SCCA-IgM activity
increased the sensitivity to 92.5% and specificity to 62.1%. There were positive
significant correlations between SCCA-IgM and each of AFU (r=0.296, P=0.005) and
AFP (r=0.284, P=0.007) and no correlation between AFP and AFU. All markers did
not correlate with the tumor size or affected by the Child score. The significant
difference between SCCA-IgM and AFU levels among HCC and cirrhotic patients
suggests their use as potential diagnostic tools and allows identifying a new
group of HCC patients even in the absence of elevated AFP.
PMID- 25129444
TI - Proteomic analysis of formalin-fixed paraffin-embedded glomeruli suggests
depletion of glomerular filtration barrier proteins in two-kidney, one-clip
hypertensive rats.
AB - BACKGROUND: It is well known that hypertension may cause glomerular damage, but
the molecular mechanisms involved are still incompletely understood. METHODS: In
the present study, we used formalin-fixed paraffin-embedded (FFPE) tissue to
investigate changes in the glomerular proteome in the non-clipped kidney of two
kidney one-clip (2K1C) hypertensive rats, with special emphasis on the glomerular
filtration barrier. 2K1C hypertension was induced in 6-week-old Wistar Hannover
rats (n = 6) that were sacrificed 23 weeks later and compared with age-matched
sham-operated controls (n = 6). Tissue was stored in FFPE tissue blocks and later
prepared on tissue slides for laser microdissection. Glomeruli without severe
morphological damage were isolated, and the proteomes were analysed using liquid
chromatography-tandem mass spectrometry. RESULTS: 2K1C glomeruli showed reduced
abundance of proteins important for slit diaphragm complex, such as nephrin,
podocin and neph1. The podocyte foot process had a pattern of reduced abundance
of transmembrane proteins but unchanged abundances of the podocyte cytoskeletal
proteins synaptopodin and alpha-actinin-4. Lower abundance of important
glomerular basement membrane proteins was seen. Possible glomerular markers of
damage with increased abundance in 2K1C were transgelin, desmin and acyl-coenzyme
A thioesterase 1. CONCLUSIONS: Microdissection and tandem mass spectrometry could
be used to investigate the proteome of isolated glomeruli from FFPE tissue.
Glomerular filtration barrier proteins had reduced abundance in the non-clipped
kidney of 2K1C hypertensive rats.
PMID- 25129446
TI - Transport priorities, risk perception and worry associated with mode use and
preferences among Norwegian commuters.
AB - There is currently scant research on the role of transport priorities, risk
perception and worry for travel mode use and preferences. The present study aims
to examine these factors in relation to mode use and preferences among Norwegian
commuters. A web-based survey was conducted in a randomly obtained representative
sample of daily commuters in the extended greater Oslo area (n=690). The results
showed that those who prioritized efficiency and flexibility tended to commute by
car, while those who prioritized safety and comfort used public (e.g. metro,
tram, and train) or active (e.g. walking and cycling) transport. In a free choice
scenario, the respondents who prioritized flexibility reported a preference for
using a car, whereas those who prioritized safety and comfort preferred public
and active transport for their commuter travels. Risk perception of high impact
events, such as terrorism and major accidents, as well as risk perception related
to personal impact risks (theft, violence etc.) were related to car use on
commuter travels. Transport-related worry exerted weak influences on mode use and
preferences. Increased speed on rail transport and more frequent departures may
be effective in reducing car use on commuter travels. Risk communication should
focus on highlighting the low risk of experiencing security and safety issues in
the public transport sector, and this message should be complemented by efforts
to reduce the probability of negative events affecting public transport.
PMID- 25129445
TI - Fluoxetine modulates breast cancer metastasis to the brain in a murine model.
AB - BACKGROUND: Despite advances in the treatment of primary breast tumors, the
outcome of metastatic breast cancer remains dismal. Brain metastases present a
particularly difficult therapeutic target due to the "sanctuary" status of the
brain, with resulting inability of most chemotherapeutic agents to effectively
eliminate cancer cells in the brain parenchyma. A large number of breast cancer
patients receive various neuroactive drugs to combat complications of systemic
anti-tumor therapies and to treat concomitant diseases. One of the most
prescribed groups of neuroactive medications is anti-depressants, in particular
selective serotonin reuptake inhibitors (SSRIs). Since SSRIs have profound
effects on the brain, it is possible that their use in breast cancer patients
could affect the development of brain metastases. This would provide important
insight into the mechanisms underlying brain metastasis. Surprisingly, this
possibility has been poorly explored. METHODS: We studied the effect of
fluoxetine, an SSRI, on the development of brain metastatic breast cancer using
MDA-MB-231BR cells in a mouse model. RESULTS: The data demonstrate that
fluoxetine treatment increases the number of brain metastases, an effect
accompanied by elevated permeability of the blood-brain barrier, pro-inflammatory
changes in the brain, and glial activation. This suggests a possible role of
brain-resident immune cells and glia in promoting increased development of brain
metastases. CONCLUSION: Our results offer experimental evidence that neuroactive
substances may influence the pathogenesis of brain metastatic disease. This
provides a starting point for further investigations into possible mechanisms of
interaction between various neuroactive drugs, tumor cells, and the brain
microenvironment, which may lead to the discovery of compounds that inhibit
metastasis to the brain.
PMID- 25129447
TI - Vaccination and malaria prophylaxis among Greek international travelers to Asian
destinations.
AB - BACKGROUND: International travel is rapidly increasing worldwide, and the
greatest increases have occurred in tropical and subtropical areas. The aim of
the survey was to investigate the pre-travel health-seeking practices of
travelers to Asian destinations. METHODS: A questionnaire-based survey was
conducted at the Athens International Airport between the 1st of November 2011
and the 30th of April 2013. RESULTS: A total of 1666 adult travelers participated
in the study, and 69.7% were men. The mean age of the participants was 39 years.
Previous travel to tropical countries was reported by 69% of the participants.
The most frequent destination was the Indian subcontinent (45.0%). The main
reasons for travel were visiting friends and relatives (VFRs; 36.5%) and business
(32.4%). Most of the participants traveled for <1 month (51.4%). Only 24.5%
pursued pre-travel consultations. Vaccinations were administered to 14.4% of the
participants, and of those, 77%, 73%, and 32.5% received hepatitis A,
tetanus/diphtheria, and typhoid vaccines, respectively. Malaria prophylaxis was
given to 12.2% of the participants. Logistic regression analysis revealed that
being male and unemployed, having an elementary level of education, traveling to
visiting friends and relatives, and short durations of travel were significant
determinants of not seeking pre-travel consultations. CONCLUSION: Significant
gaps were revealed in the vaccinations and malaria prophylaxes of travelers
departing to Asia. Specific educational tools should be developed to improve the
awareness of travelers to high-risk destinations.
PMID- 25129448
TI - A multicenter point-prevalence survey of antibiotic use in 13 Chinese hospitals.
AB - BACKGROUND: The use of antibiotics is considered a major determinant of the
development of resistance in organisms. This study assessed current patterns of
antibiotic prescription and provides background for quality improvement in
general hospitals in Hubei, China. METHODS: A point-prevalence study was
performed in November 2008. All inpatients on the day of the survey were included
in the analysis. RESULTS: On the day of the study, 6904 patients (56%) were
receiving antibiotic therapy; the highest rate occurred in the ICU (90%), and the
lowest occurred in the medical wards (39%). The most commonly used antibiotics
were beta-lactam antibiotics, including cephalosporins (40%) and piperacillin
(19%), followed by fluoroquinolones (14%). CONCLUSIONS: Our data indicated a high
rate of antibiotic use in Chinese hospitals. These findings suggest important
areas for intervention and the implementation of antibiotic stewardship policies
in Chinese hospitals. A multi-faceted strategy should be implemented at the
national level in China and should include education, regulation, and greater
financial support from the government.
PMID- 25129449
TI - Response of the seagrass Posidonia oceanica to different light environments:
Insights from a combined molecular and photo-physiological study.
AB - Here we investigated mechanisms underlying the acclimation to light in the marine
angiosperm Posidonia oceanica, along its bathymetric distribution (at -5 m and
25 m), combining molecular and photo-physiological approaches. Analyses were
performed during two seasons, summer and autumn, in a meadow located in the
Island of Ischia (Gulf of Naples, Italy), where a genetic distinction between
plants growing above and below the summer thermocline was previously revealed. At
molecular level, analyses carried out using cDNA-microarray and RT-qPCR, revealed
the up-regulation of genes involved in photoacclimation (RuBisCO, ferredoxin,
chlorophyll binding proteins), and photoprotection (antioxidant enzymes,
xanthophyll-cycle related genes, tocopherol biosynthesis) in the upper stand of
the meadow, indicating that shallow plants are under stressful light conditions.
However, the lack of photo-damage, indicates the successful activation of defense
mechanisms. This conclusion is also supported by several responses at
physiological level as the lower antenna size, the higher number of reaction
centers and the higher xanthophyll cycle pigment pool, which are common plant
responses to high-light adaptation/acclimation. Deep plants, despite the lower
available light, seem to be not light-limited, thanks to some shade-adaptation
strategies (e.g. higher antenna size, lower Ek values). Furthermore, also at the
molecular level there were no signs of stress response, indicating that, although
the lower energy available, low-light environments are more favorable for P.
oceanica growth. Globally, results of whole transcriptome analysis displayed two
distinct gene expression signatures related to depth distribution, reflecting the
different light-adaptation strategies adopted by P. oceanica along the depth
gradient. This observation, also taking into account the genetic disjunction of
clones along the bathymetry, might have important implications for micro
evolutionary processes happening at meadow scale. Further investigations in
controlled conditions must be performed to respond to these questions.
PMID- 25129450
TI - How to minimize lymphoceles and treat clinically symptomatic lymphoceles after
radical prostatectomy.
AB - The development of a lymphocele after pelvic surgery is a well-documented
complication, especially where pelvic lymph node dissection (PLND) is part of the
operation. However, not all lymphoceles are symptomatic and require treatment.
Most lymphoceles spontaneously resolve, and even lymphoceles that become
symptomatic may resolve without any intervention. Robotic assisted radical
prostatectomy (RARP) is a common operation in urology where PLND is likely to be
performed in intermediate and high-risk prostate cancer patients. The rationale
for performing a PLND in prostate cancer is for accurate staging and potential
therapeutic benefits. However, due to potential intraoperative and postoperative
complications there is still a debate regarding the value of PLND in prostate
cancer. In this review, we will discuss the potential risk factors to be aware of
in pelvic surgery in order to minimize the formation of a lymphocele, along with
the management for clinically significant lymphoceles.
PMID- 25129451
TI - Effect of ecto-5'-nucleotidase (eN) in astrocytes on adenosine and inosine
formation.
AB - ATP is a gliotransmitter released from astrocytes. Extracellularly, ATP is
metabolized by a series of enzymes, including ecto-5'-nucleotidase (eN; also
known as CD73) which is encoded by the gene 5NTE and functions to form adenosine
(ADO) from adenosine monophosphate (AMP). Under ischemic conditions, ADO levels
in brain increase up to 100-fold. We used astrocytes cultured from 5NTE (+/+) or
5NTE (-/-) mice to evaluate the role of eN expressed by astrocytes in the
production of ADO and inosine (INO) in response to glucose deprivation (GD) or
oxygen-glucose deprivation (OGD). We also used co-cultures of these astrocytes
with wild-type neurons to evaluate the role of eN expressed by astrocytes in the
production of ADO and INO in response to GD, OGD, or N-methyl-D-aspartate (NMDA)
treatment. As expected, astrocytes from 5NTE (+/+) mice produced adenosine from
AMP; the eN inhibitor alpha,beta-methylene ADP (AOPCP) decreased ADO formation.
In contrast, little ADO was formed by astrocytes from 5NTE (-/-) mice and AOPCP
had no significant effect. GD and OGD treatment of 5NTE (+/+) astrocytes and 5NTE
(+/+) astrocyte-neuron co-cultures produced extracellular ADO levels that were
inhibited by AOPCP. In contrast, these conditions did not evoke ADO production in
cultures containing 5NTE (-/-) astrocytes. NMDA treatment produced similar
increases in ADO in both 5NTE (+/+) and 5NTE (-/-) astrocyte-neuron co-cultures;
dipyridamole (DPR) but not AOPCP inhibited ADO production. These results indicate
that eN is prominent in the formation of ADO from astrocytes but in astrocyte
neuron co-cultures, other enzymes or pathways contribute to rising ADO levels in
ischemia-like conditions.
PMID- 25129452
TI - Regional differences between US and Europe in radiological osteoarthritis and
self assessed quality of life in patients undergoing total hip arthroplasty
surgery.
AB - Precise indications for THA remain unclear and regional differences might exist
in selecting patients for surgery. In this study we investigate radiological OA
grade and self-reported quality of life in 909 patients undergoing THA in 16
centers across US and Europe. Patients in US were younger and had higher BMI.
More patients with mild Tonnis OA grade underwent surgery in the US compared to
Europe. Patients in the US had significantly higher pain VAS and significantly
lower SF-36 Physical, while having significantly higher EQ-VAS scores
preoperatively. Patient demographics and disease severity according to
radiological OA grade and self-reported survey scores vary between the United
States and Europe. This knowledge can be used in the interpretation of US and
European based studies on outcome following THA.
PMID- 25129453
TI - The impact of community support initiatives on the stigma experienced by people
living with HIV/AIDS in South Africa.
AB - In the current context of human resource shortages in South Africa, various
community support interventions are being implemented to provide long-term
psychosocial care to persons living with HIV/AIDS (PLWHA). However, it is
important to analyze the unintended social side effects of such interventions in
regards to the stigma felt by PLWHA, which might threaten the successful
management of life-long treatment. Latent cross-lagged modeling was used to
analyze longitudinal data on 294 PLWHA from a randomized controlled trial (1) to
determine whether peer adherence support (PAS) and treatment buddying influence
the stigma experienced by PLWHA; and (2) to analyze the interrelationships
between each support form and stigma. Results indicate that having a treatment
buddy decreases felt stigma scores, while receiving PAS increases levels of felt
stigma at the second follow up. However, the PAS intervention was also found to
have a positive influence on having a treatment buddy at this time. Furthermore,
a treatment buddy mitigates the stigmatizing effect of PAS, resulting in a small
negative indirect effect on stigma. The study indicates the importance of looking
beyond the intended effects of an intervention, with the goal of minimizing any
adverse consequences that might threaten the successful long-term management of
HIV/AIDS and maximizing the opportunities created by such support.
PMID- 25129455
TI - Evaluation of TAZ expression and its effect on tumor invasion and metastasis in
human glioma.
AB - OBJECTIVES: To evaluate the expression of TAZ and its role in tumor invasion and
metastasis in human glioma. METHODS: The expression of TAZ protein was measured
in 48 samples of surgically resected human glioma and 13 samples of normal brain
tissues using immunohistochemistry. TAZ was knocked down by a retrovirus-mediated
TAZ shRNA in a glioma cell line, SNB19. Transwell cell migration and invasion
assays were used to determine migration and invasion of SNB19 cells. RESULTS: The
positive expression rate of TAZ protein in glioma tissues was significantly
higher than that in normal brain tissues (79.2% vs. 15.4%, P<0.001). Furthermore,
clinical analysis suggested that the positive expression rate of TAZ protein in
poorly differentiated tumor tissues was significantly higher as compared with
that in well differentiated tissues (96.0% vs. 60.9%, P<0.01). TAZ was
significantly knocked down by TAZ shRNA (P<0.001), and TAZ knockdown
significantly reduced cell migration and invasion (P<0.01, respectively) in SNB19
cells. CONCLUSIONS: TAZ protein overexpression is observed in human glioma and
its elevated expression is significantly correlated with poor differentiation.
TAZ knockdown prominently reduces cell migration and invasion in SNB19 cells,
suggesting that TAZ may play a key role in the initiation and progression of
human glioma.
PMID- 25129454
TI - Looking Beyond Health-Related Quality of Life: Predictors of Subjective Well
Being among People Living with HIV in the Netherlands.
AB - Health care interventions are increasingly expected to improve subjective well
being (SWB) rather than health-related quality of life (HRQOL) only. However,
little is known about how HRQOL and other relevant quality of life (QOL) domains
relate to SWB among people living with HIV. People living with HIV treated in
Dutch HIV centers (n = 191) completed a cross-sectional survey on SWB, HRQOL, and
other QOL domains (social, financial, sexual, and environmental well-being). In
bivariate analyses, all QOL domains were significantly related to SWB (r = .17 to
.42). In structural equation models, physical health (beta = .14; p < .05),
mental health (beta = .27; p < .01), and environmental well-being (beta = .41; p
< .01) directly predicted SWB, while financial and social well-being explained
SWB indirectly. Thus, environmental well-being and mental health are the main
predictors of SWB, and physical health, social well-being, and financial well
being to a lesser extent. Given that most of HIV-care is directed at improving
physical health, from the perspective of promoting SWB HIV care should also be
directed at other life domains.
PMID- 25129456
TI - Expressions of oncogenes c-fos and c-myc in skin lesion of cutaneous squamous
cell carcinoma.
AB - OBJECTIVES: To explore the expressions of c-fos and c-myc in skin lesion of
cutaneous squamous cell carcinoma (CSCC). METHODS: Using retrospective analysis,
73 cases of CSCC were selected from Department of Dermatology, the Second
Affiliated Hospital of Xi'an Jiaotong University, which were removed between
January 2000 and January 2012. It was considered as experimental group.
Meanwhile, 11 cases of normal skin specimens of non tumor patients were selected
as control group. The expression level of c-fos and c-myc was compared in the two
groups. RESULTS: The expressions of c-fos [72.60% (53/73)] and c-myc [83.56%
(61/73)] in experimental group were statistically significant (P<=0.05) compared
with control group (0%). Expression of c-myc protein was negatively related to
differentiation of CSCC. The difference was statistically significant
(chi(2)=7.26, P=0.001<0.05). While expression of c-fos protein was positively
related to differentiation of CSCC, which was statistically significant
(chi(2)=7.47, P=0.001 2<0.025). CONCLUSIONS: The expression level of c-fos and c
myc can be used as an important indicator of CSCC differentiation, and it has
closely connection with the differentiated degree, which can guide clinical
prognosis.
PMID- 25129457
TI - HTRA1 gene expression in gastric epithelial cells.
AB - OBJECTIVES: To explore HtrA1 gene expression and its regulation in human gastric
cancers. METHODS: The HtrA1 mRNA levels were examined by QPCR analysis and
confirmed its expression with Northern blot analysis. The HtrA1 protein levels in
all six gastric epithelial cell lines were investigated by Western blot analysis.
Gene copy number was accessed and then sequenced the coding region from each mRNA
in all six cell lines. The HtrA1 promoter region DNA methylation status was
detected by using bisulfite sequencing analysis. Effect of decitabine and TSA on
HTRA1 expression in gastric cancer cell line was determined by RTPCR. RESULTS:
HIC analysis indicated that HtrA1 was highly expressed in normal epithelium, but
dramatically down-regulated in gastric carcinoma tissues and variably expressed
in tumor-adjacent tissues. HtrA1 gene expression was dramatically decreased in
gastric carcinoma cells compared to non-tumorigenic counterparts. The HtrA1 gene
loss in any of the 4 breast cancer cell lines was not detected. Total 14 CpGs in
this region were all methylated in gastric cancer cells, whereas two normal
cells, GES-1 and HFI-145, were having several unmethylated cytosines in this
region. HtrA1 showed as ~Mr 44,000, Expression of HtrA1 protein was not observed
in any of the four gastric cancer cell lines, BGC-823, MKN-45, SGC-7901and MKN
28. HtrA1 expression was observed in the HFI-145and GES-1 cell lines.
CONCLUSIONS: The epigenetic silencing for HtrA1 gene expression could provide a
possible strategy for re-activating HtrA1 gene expression in gastric cancer
cells, thus facilitating further investigation of HtrA1's role in chemotherapy.
PMID- 25129458
TI - Influence of As2O3 combined with ginsenosides Rg3 on inhibition of lung cancer
NCI-H1299 cells and on subsistence of nude mice bearing hepatoma.
AB - OBJECTIVES: To study the effect of arsenic trioxide (As2O3) combined with
ginsenosides Rg3 on inhibiting the NCI-H1299 lung cancer cells and subsistence in
nude mice bearing hepatoma. METHODS: MTT method was used to measure the
inhibition effect of As2O3 combined Rg3 on NCI-H1299 cells, and the proliferation
inhibiting effect was observed via establishing the transplanted tumor model in
vitro. A total of 40 tumor-bearing nude mice were randomly divided into normal
saline group, As2O3, Rg3 and As2O3+Rg3 group. Transplantation tumor model of lung
cancer in nude mice was constructed, followed by injection of certain
concentrations of normal saline, As2O3, ginseng saponin Rg3 and As2O3+Rg3 every
day. The survival duration and the tumors size of the mice were recorded and the
Kaplan-Meier curve was made; microscopic observation of apoptosis of tumor cells
in vivo was done using TUNEL staining. RESULTS: After 72 h of injection,
inhibition rate of tumor cell in normal saline group, As2O3 group, Rg3 group and
As2O3+Rg3 group was (5.66+/-0.31)%, (65.58+/-4.75)%, (44.69+/-3.32)% and (82.67+/
5.43)%, respectively. Inhibition rate of tumor cell in As2O3 group, Rg3 group and
As2O3+Rg3 group was significantly higher than that of normal saline group
(P<0.01); inhibition rate of tumor cells of As2O3+Rg3 group was significantly
higher than that of the two groups given As2O3 or Rg3 alone (P<0.01). The tumor
volume of As2O3 group, Rg3 group and As2O3+Rg3 group shrank to (65.38+/-3.25)%,
(77.68+/-3.43)% and (42.65+/-3.55)% of the original, tumor volume of saline group
was 1.21 times of the original size (P<0.01); Median survival of saline group,
Rg3 group, As2O3 group were significantly shorter than that of As2O3+Rg3 group
(P<0.01); co-ordinated intervention ability of As2O3+Rg3 on NCI-H1299 cell was
significantly higher than that of As2O3 or Rg3, separately. CONCLUSIONS: As2O3
combined with Rg3 can significantly inhibit proliferation of NCI-H1299 cells in
lung cancer, prolong survival of tumor-bearing nude mice, and promote tumor cell
apoptosis, and have significant effect on lung cancer treatment.
PMID- 25129459
TI - MicroRNA-184 promotes proliferation ability of glioma cells by regulating FOXO3.
AB - OBJECTIVES: To investigate the effect of microRNA (miR-184) on regulating the
genesis, development and proliferation of glioma cells. METHODS: Lipidosome was
used to transfect miR-184 mimic and inhibitor to glioma cell line, and the cell
proliferation ability changes were determined by MTT and plate cloning experiment
after the transfection. WB test was used to measure the levels of cyclinD1, p27
and FOXO3. Meanwhile, QPCR was used to detect miR-184 expression in glioma cell
line, glioma tissues and adjacent tissues. Luciferase experiment was used to test
3'UTR gene targeting regulation of miR-184 and FOXO3. RESULTS: QPCR results
showed a significant lower miR-184 expression level in glioma cell line and
glioma tissues than that in juxtacancerous tissue. MTT and plate cloning
experiments have shown that after over-expressing of miR-184, the cell
proliferation capacity of glioma U87 and T98G was significantly increased, which
was significantly inhibited after the inhibition of miR-184. WB results showed a
lower expression level of p27 in U87 and T98G cells, and a higher expression
level of cyclinD1 after over-expressing of miR-184 was observed. However, a lower
expression level of cyclinD1 and a higher expression level of p27 after the
inhibition of miR-184. The luciferase activity was inhibited after the over
expressing of miR-184. CONCLUSIONS: MiR-184 can affect the proliferation
abilities of glioma cells and regulate the cell cycle related protein. It plays
an important role in the occurrence and development of gliomas.
PMID- 25129460
TI - Lentivirus vectors construction of SiRNA targeting interference GPC3 gene and its
biological effects on liver cancer cell lines Huh-7.
AB - OBJECTIVES: To build GPC3 gene short hairpin interference RNA (shRNA) slow virus
vector, observe expression of Huh-7 GPC3 gene in human liver cell line
proliferation apoptosis and the effect of GPC3 gene influencing on liver cancer
cell growth, and provide theoretical basis for gene therapy of liver cancer.
METHODS: Hepatocellular carcinoma cell line Huh-7 was transfected by a RNA
interference technique. GPC3 gene expression in a variety of liver cancer cell
lines was detected by fluorescence quantitative PCR. Targeted GPC3 gene sequences
of small interfering RNA (siRNA) PGC-shRNA-GPC3 were restructured. Stable
expression cell lines of siRNA were screened and established with the help of
liposomes (lipofectamine(TM2000)) as carrier transfection of human liver cell
lines. In order to validate siRNA interference efficiency, GPC3 siRNA mRNA
expression was detected after transfection by using RT-PCR and Western blot. The
absorbance value of the cells of blank group, untransfection group and
transfection group, the cell cycle and cell apoptosis were calculated, and
effects of GPC3 gene on Huh-7 cell proliferation and apoptosis were observed.
RESULTS: In the liver cancer cell lines Huh-7, GPC3 gene showed high expression.
PGC-shRNA-GPC3 recombinant plasmid was constructed successfully via sequencing
validation. Stable recombinant plasmid transfected into liver cancer cell lines
Huh-7 can obviously inhibit GPC3 mRNA expression level. CONCLUSIONS: The targeted
GPC3 siRNA can effectively inhibit the expression of GPC3.
PMID- 25129461
TI - Effect of Fibulin-5 on cell proliferation and invasion in human gastric cancer
patients.
AB - OBJECTIVES: To explore the effect of Fibulin-5 expression on cell proliferation
and invasion in human gastric cancer patients. METHODS: Fibulin-5 expression was
detected in 56 samples of surgically resected gastric cancer and paired
noncancerous tissues using qRT-PCR and immunoblotting. Fibulin-5 was knocked down
by Fibulin-5 shRNA in MGC-803 cells, then BrdU cell proliferation and transwell
invasion assays were used to determine cell proliferation and invasion. RESULTS:
The level of Fibulin-5 mRNA in gastric cancer tissues was significantly higher as
compared with that in normal tumor-adjacent tissues (P<0.05). Otherwise, the
level of Fibulin-5 protein in cancer and noncancerous tissues was consistent with
mRNA expression (P<0.05). Fibulin-5 protein expression in tumor tissues with
poorly differentiated, lymph node metastasis and advanced TNM tumor stage was
significantly higher (P<0.05, respectively). Fibulin-5 was obviously knocked down
by Fibulin-5 shRNA (P<0.05), and Fibulin-5 knockdown significantly inhibited cell
proliferation and invasion in MGC-803 cells (P<0.05, respectively). CONCLUSIONS:
The high-expression of Fibulin-5 is associated with the malignant
clinicopathologic parameters in gastric cancer and Fibulin-5 knockdown inhibits
cell proliferation and invasion in MGC-803 cells, suggesting Fibulin-5 may act as
a key factor in the progression of gastric cancer.
PMID- 25129462
TI - Effect of simvastatin on expression of IL17, HMGB1 and TLR4 in LN kidney tissues
of rats.
AB - OBJECTIVES: To observe the intervention influence and effect of simvastatin on
the expression of interleukin 17 (LI17), high mobility group protein 1 (HMGB1)
and TLR4 path in Lupus nephritis (LN) rats. METHODS: A total of 28 BSXSB male
mice with LN (16 weeks) were randomly divided into observation group and the
comparison group, observation group was given 6 mg*kg(-1)*d(-1) simvastatin in
0.1% PBS lavage for 4 weeks, the comparison group was not given any treatment.
Blood urea nitrogen (BUN) level and urine trace albumin (Scr) level of two groups
were determined. The expression of IL17, HMGB1 and TLR4 protein was detected
using immune histochemical method, and the kidney histological damage was
observed. RESULTS: BNU, LI17, HMGB1, TLR4 protein and HMGB1 mRNA in observation
group was significantly lower than that in control group (P<0.05); There was no
statistical difference of Scr level between two groups (P>0.05). Histological
observation showed glomerular lesions integral of observation group was obviously
lower than that of control group. CONCLUSIONS: Simvastatin can reduce the
expression of IL17, HMGB1 and TLR4 protein in LN mice, thereby can inhibit the
autoimmune response as a potential treatment function of LN.
PMID- 25129463
TI - To investigate the effect of osteoporosis and intervertebral disc degeneration on
the endplate cartilage injury in rats.
AB - OBJECTIVES: To investigate the effect of osteoporosis and intervertebral disc
degeneration on the endplate cartilage injury in rats. METHODS: A total of 48
female Sprague Dawley rats (3 months) were randomly divided into Groups A, B, C
and D with 12 rats in each group. Osteoporosis and intervertebral disc
degeneration composite model, simple degeneration model and simple osteoporosis
model were prepared in Groups A, B and C respectively. After modeling, four rats
of each group at 12th, 18th and 24th week were sacrificed. Intervertebral height
of cervical vertebra C6/C7 was measured. Micro-CT was used to image the endplate
of cephalic and caudal cartilage at C6/C7 intervertebral disc. Abraded area rate
of C6 caudal and C7 cephalic cartilage endplate was calculated, and then C6/C7
intervertebral disc was routinely embedded and sectioned, stained with safranin O
to observe histological changes microscopically. RESULTS: At 12, 18 and 24 weeks,
intervertebral disc height of C6/C7 were (0.58+/-0.09) mm, (0.53+/-0.04) mm and
(0.04+/-0.06) mm in Group A rats, (0.55+/-0.05) mm, (0.52+/-0.07) mm and (0.07+/
0.05) mm in Group B rats. At 24th week, intervertebral disc height of Group A
rats was significantly lower than that of Group B rats (P<0.05); intervertebral
disc height of Groups A and B rats at each time point were significantly lower
than that of Groups C and D (P<0.05). There was no significantly statistical
difference of intervertebral disc height between Groups C and D (P>0.05). At 12
and 18 weeks, the abraded rate of C6 caudal and C7 cephalic cartilage endplate in
Group A rats were significantly higher than that in Groups B, C and D rats
(P<0.05); the abraded rate in Group B was significantly higher than that in
Groups C and D (P>0.05). Microscopic observation of CT showed that ventral
defects in C6 caudal or C7 cephalic cartilage endplate in Groups A and B appeared
after 12 weeks of modeling; obvious cracks were found in front of the C6 and C7
vertebral body, and cartilage defect shown the trend of "repairing" at 18 and 24
weeks after modeling. CONCLUSIONS: Intervertebral disc degeneration and
osteoporosis can cause damage to the cartilage endplate. Co-existence of these
two factors can induce more serious damage to the endplate, which has possitive
correlation with intervertebral disc degeneration. Osteoporosis plays a certain
role in intervertebral disc degeneration process, and accelerates the
degeneration of intervertebral disc in a specific time window.
PMID- 25129464
TI - Effects of aspirin on fracture healing in OPF rats.
AB - OBJECTIVES: To study the effect of aspirin on healing process of osteoporotic
fracture (OPF) in rats. METHODS: A total of 50 female Wistar rats aged 3 months
were randomly divided into observation group and control group, castration method
was adopted to establish the osteoporosis (OP) model. After artificial preparing
fractures on the midpoint of left femur, fixing gram needle intramedullary, OPF
modeling was complete. Aspirin lavage of 33 mg once a day was adopted in
observation group after modeling, same amount of normal saline was used in the
control as placebo. From each group, selected 5 rats at the 2nd, 4th, 8th and
12th week after modeling to measure the bone mineral density (BMD) and
histological examination of the fracture callus, radiology observation was
conducted at the 8th and 12th week. Left femur biomechanical measurement was
taken at the 12th week. RESULTS: BMD values of observation group at each time
point were significantly higher than that of the control group after modeling
(P<0.05); Histological observation showed that at the 8th week, the endochondral
ossification process of observation group was faster than that of observation
group, with fuzzy fracture line in observation group and clear fracture line in
observation group; at the 12th week, fracture line disappeared in observation
group, fracture line of the control group was fuzzy at the same time; three-point
bending load of the left femur in observation group rats was significantly higher
than that of control group after 12 weeks (P<0.05). CONCLUSIONS: Aspirin can
accelerate the healing of new callus in OPF rats, increase bone density and
biomechanics strength, and promote fracture healing of osteoporotic rats.
PMID- 25129465
TI - Nerve protective effect of Baicalin on newborn HIBD rats.
AB - OBJECTIVES: To investigate the nerve protective effect and mechanism of baicalin
on newborn rats with hypoxic ischemic brain damage (HIBD). METHODS: A total of 64
SD newborn rats were randomly divided into control group, model group, nerve
growth factor group and baicalin group, with 16 in each group. Left carotid
artery ligation method was adopted to establish the HIBD model except for in
control group, which was treated with intraperitoneal injection of salin e10
mL/kg for 3 d. After oxygen recovery on hypoxia ischemia rats, intraperitoneal
injection of saline 10 mL/kg was adopted in model group for 3 d. Intraperitoneal
injection of nerve growth factor injection 50 MUg/kg per day was adopted in nerve
growth factor group for 3 d; intraperitoneal injection of radix scutellariae 16
mg/kg per day was adopted in baicalin group for 3 d after modeling. Four rats of
each group were sacrificed at Day 1, 2, 3, 7 for microscopic observation of
pathological morphological changes in brain tissue after HE staining, S-P
immunohistochemical method was used for observation of Fas and FasL expression in
brain cells. RESULTS: Neat structure of cells was observed in control group;
edema cells in disordered arrangement was observed in model group, with some
cells necrosis and cavity change; tissue injury in nerve growth factor group and
baicalin group was significantly lighter than that in model group; Fas and FasL
expression in model group, nerve growth factor group and baicalin group were
significantly higher than that in control group at different time points
(P<0.05); Fas and FasL expression in nerve growth factor group and baicalin group
were significantly lower than that in model group at different time points
(P<0.05); There was no statistical difference of Fas, FasL expression at each
time point between nerve growth factor group and baicalin group (P>0.05).
CONCLUSIONS: Baicalin can reduce expression of Fas and FasL in HIBD rats, inhibit
apoptosis of nerve cells, thus achieve the protective effect on HIBD rat nerves.
PMID- 25129466
TI - H nuclear magnetic resonance-based metabolomics reveals sex-specific metabolic
changes of gastrodin intervention in rats.
AB - OBJECTIVES: To explore (1)H nuclear magnetic resonance-based metabolomics on sex
specific metabolic changes of gastrodin intervention in rats. METHODS: In this
research, (1)H NMR-based metabolomics was used for the first time to investigate
metabolic changes following chronic intervention with gastrodin in rats. RESULTS:
24 endogenous metabolites were identified. Body weight, daily diet and the total
volume of urine in in each day of each rat were measured synchronously.
Modifications in 12 metabolites were observed following gastrodin intervention,
indicating gastrodin-induced alterations in carbohydrate and energy metabolism.
Interestingly, these metabolic changes were not totally identical in female and
male rats. Some metabolic changes arising from gastrodin intervention showed
sexual dimorphism including LDL/VLDL and lactate which were on the decrease in
the female but on the increase in the male, together with arginine/ornithine,
creatine, and glycerol which were on the increase in the female but on the
decrease in the male. While the decrease in pyruvate, succinate and glutamate was
only shown in the male and the increase in valine, alpha-ketoglutarate, glycine
and glucose was only in the female. CONCLUSIONS: This research shows the sex
specific metabolic response to GAS intervention, weather GAS is a healthy dietary
supplement for the male merits further investigation.
PMID- 25129467
TI - Protective effect of pioglitazone on kidney injury in diabetic rats.
AB - OBJECTIVES: To investigate the protective effect of pioglitazone on kidney injury
in diabetic rat model and its mechanisms. METHODS: Forty healthy Sprague Dawley
rats were selected and randomly divided into five groups, with 8 rats in each
group. Group A served as control group and were administered with sterile citrate
buffer (i.p.) as placebo. Groups B, C, D and E rats were injected (i.p.) with
streptozotocin to induce type I diabetes. Diabetic rats in Group B were
intragastrically administered with sterile saline solution alone. Groups C, D and
E rats were intragastrically given pioglitazone hydrochloride suspension at doses
of 10, 20, 30 mg/kg per day, respectively. After eight weeks of treatment, all
rats were anesthetized and blood was withdrawn from the abdominal aortic for
detection of hemoglobin A1c, serum creatinine (SCr) and blood urea nitrogen (BUN)
levels. Rats were then sacrificed and the left kidney was excised for calculation
of kidney hypertrophy index (KHI), observation of renal pathological changes
using light microscope and electron microscope. Mean glomerular cross-sectional
areas (MGA), mean glomerular volume (MGV), glomerular basement membrane thickness
and foot process fusion ratio were calculated. RT-PCR was employed for detection
of podocalyxin (PCX) protein expression. RESULTS: Results showed that levels of
hemoglobin A1c, BUN, SCr in Groups B, C, D and E rats were significantly higher
than those in Group A (P<0.05), while BUN and SCr levels in rats of Groups C, D
and E were significantly lower than those in Group B (P<0.05). KHI, MGA and MGV
levels were significantly higher in Groups B, C, D and E rats than those in Group
A (P<0.05); KHI and MGA levels in Group B rats were significantly higher than
those in Groups C, D and E (P<0.05) and MGV in Groups D and E was significantly
lower than that in Groups B and C (P<0.05). Histology study showed normal
glomerulus structure, morphology, volume, endothelial cells and mesangial cells
as well as clear glomerular capillary in Group A rats. Renal mesangial matrix
proliferation and expansion of glomerulus cavities in Groups B, C, D and E were
observed. However, damage degree in Groups C, D and E were more moderate than
that in Group B. CONCLUSIONS: Pioglitazone can reduce kidney damage in diabetic
rats, which may be attributed to its role in increasing glomerular PCX protein
expression and inhibiting urinary excretion of PCX, and its effect is dose
dependent.
PMID- 25129468
TI - Role of immune dysfunction in pathogenesis of type 1 diabetes mellitus in
children.
AB - OBJECTIVES: To investigate the function of cytokines, chemokines, and regulatory
T cells (Tregs) in the pathogenesis of type 1 diabetes mellitus (T1DM) in
children. METHODS: A total of 35 children with T1DM and 30 healthy controls were
enrolled in this study. Levels of serum cytokines (IL-1alpha, IL-6, IL-10, IL-12,
and TNF-alpha) and chemokines (MIP-1alpha, MIP-1alpha and MCP-1) were detected by
enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells (PBMCs)
were isolated and culture supernatant of phytohaemagglutinin (PHA)-stimulated
PBMCs was subjected to ELISA for levels of cytokines (IL-1alpha, IL-6, IL-10, IL
12 and TNF-alpha) in T1DM and control group. Furthermore, flow cytometry was used
to determine the percentage of Tregs in PBMCs of two groups. RESULTS: Levels of
serum cytokines including IL-1alpha, IL-6, IL-10 and TNF-alpha as well as
chemokines, such as MIP-1alpha and MIP-1alpha in children with T1DM children were
significantly higher than those in healthy controls (P<0.05, respectively). PBMCs
with PHA stimulation in T1DM group secreted more IL-1alpha and TNF-alpha (P<0.05,
respectively), but less IL-10 (P<0.05), as compared with control group.
Furthermore, the proportion of CD4(+), CD25(+), Foxp3(+), Tregs in PBMCs isolated
from children with T1DM was obviously lower than those in healthy controls
(P<0.05). CONCLUSIONS: Immune dysfunction, with upregulation of inflammatory
factors such as IL-1alpha, IL-6, TNF-alpha and MIP-1alpha, downregulation of IL
10 and Tregs, plays an important role in the pathogenesis of T1DM in children.
PMID- 25129469
TI - Role of NLRP3 and NLRP1 inflammasomes signaling pathways in pathogenesis of
rheumatoid arthritis.
AB - OBJECTIVES: To investigate the role of NLRP3 and NLRP1 inflammasomes signaling
pathways in rheumatoid arthritis (RA). METHODS: A total of 36 patients with RA
were selected, peripheral blood mononuclear cell (PBMC) and granulocyte were
separated from venous blood. RT-qPCR method was used to detect the expression
level and diversity of NLRP3 and NLRP1 in PBMC and granulocyte mRNA in patients
with RA, and detect the mRNA expression of downstream factor IL-1alpha. The
correlation between RA and the expression of NLRP3 and NLRP1 was analyzed. Normal
30 cases were set as control group. RESULTS: Expression levels of NLRP1, and
caspase-1 mRNA in PBMC of RA group were significantly lower than those of control
group (P<0.05), while there was no significant difference in expression levels of
NLRP3, ASC, IL-1alpha mRNA between these two groups (P>0.05); NLRP3, caspase-1,
and ASC mRNA expression in granulocyte of RA patients were significantly lower
than those in control group (P<0.05). There was no correlation between rheumatoid
factor and expression levels of NLRP3, ASC, caspase-1 mRNA in RA group (P>0.05);
NLRP1, IL-1alpha mRNA expression level had a negative correlation with anti
rheumatoid factor antibody (P=0.033 2, 0.034 0). CONCLUSIONS: NLRP3 and NLRP1
inflammasomes signaling pathways are involved in RA inflammatory reaction process
as protective factors, and play an important role in RA inflammatory mechanisms.
PMID- 25129470
TI - Conserved regions of Plasmodium vivax potential vaccine candidate antigens in Sri
Lanka: conscious in silico analysis of prospective conformational epitope
regions.
AB - OBJECTIVES: To do mapping and modeling of conformational B cell epitope regions
of highly conserved and protective regions of three merozoitecandidate vaccine
proteins of Plasmodium vivax (P. vivax), ie. merozoite purface protein-1 (PvMSP
1), apical membrane antigen -1 domain ? (PvAMA1-D?) and region ? of the Duffy
binding protein (PvDBP?), and to analyze the immunogenic properties of these
predicted epitopes. METHODS: 3-D structures of amino acid haplotypes from Sri
Lanka (available in GeneBank) of PvMSP-119 (n=27), PvAMA1-D? (n=21) and PvDBP?
(n=33) were modeled. SEPPA, selected as the best online server was used for
conformational epitope predictions, while prediction and modeling of protein
structure and properties related to immunogenicity was carried out with Geno3D
server, SCRATCH Protein Server, NetSurfP Server and standalonesoftware, Genious
5.4.4. RESULTS: SEPPA revealed that regions of predicted conformational epitopes
formed 4 clusters in PvMSP-I19, and 3 clusters each in PvAMA1-D? and PvDBP?, all
of which displayed a high degree of hydrophilicity, contained solvent exposed
residues, displayed high probability of antigenicity and showed positive
antigenic propensity values, that indicated high degree of immunogenicity.
CONCLUSIONS: Findings of this study revealed and confirmed that different parts
of the sequences of each of the conserved regions of the three selected potential
vaccine candidate antigens of P. vivax are important with regard to
conformational epitope prediction that warrants further laboratory experimental
investigations in in vivo animal models.
PMID- 25129471
TI - Identification and characterization of TCRgamma and TCRdelta chains in channel
catfish, Ictalurus punctatus.
AB - Channel catfish, Ictalurus punctatus, T cell receptors (TCR) gamma and delta were
identified by mining of expressed sequence tag databases, and full-length
sequences were obtained by 5'-RACE and RT-PCR protocols. cDNAs for each of these
TCR chains encode typical variable (V), diversity (D), joining (J), and constant
(C) regions. Three TCRgamma V families, seven TCRgamma J sequences, and three
TCRgamma C sequences were identified from sequencing of cDNA. Primer walking on
bacterial artificial chromosomes (BACs) confirmed that the TRG locus contained
seven TRGJ segments and indicated that the locus consists of (Vgamma3-Jgamma6
Cgamma2)-(Vgamma1n-Jgamma7-Cgamma3)-(Vgamma2-Jgamma5-Jgamma4-Jgamma3-Jgamma2
Jgamma1-Cgamma1). In comparison for TCRdelta, two V families, four TCRdelta D
sequences, one TCRdelta J sequence, and one TCRdelta C sequence were identified
by cDNA sequencing. Importantly, the finding that some catfish TCRdelta cDNAs
contain TCR Valpha-D-Jdelta rearrangements and some TCRalpha cDNAs contain Vdelta
Jalpha rearrangements strongly implies that the catfish TRA and TRD loci are
linked. Finally, primer walking on BACs and Southern blotting suggest that
catfish have four TRDD gene segments and a single TRDJ and TRDC gene. As in most
vertebrates, all three reading frames of each of the catfish TRDD segments can be
used in functional rearrangements, and more than one TRDD segment can be used in
a single rearrangement. As expected, catfish TCRdelta CDR3 regions are longer and
more diverse than TCRgamma CDR3 regions, and as a group they utilize more
nucleotide additions and contain more nucleotide deletions than catfish TCRgamma
rearrangements.
PMID- 25129472
TI - Survey of major histocompatibility complex class II diversity in pig-tailed
macaques.
AB - Pig-tailed macaques (Macaca nemestrina) serve as important models for human
infectious disease research. Major histocompatibility complex (MHC) class II
molecules are important to this research since they present peptides to CD4+ T
cells. Despite the importance of characterizing the MHC-II alleles expressed in
model species like pig-tailed macaques, to date, less than 150 MHC-II alleles
have been named for the six most common classical class II loci (DRA, DRB, DQA,
DQB, DPA, and DPB) in this population. Additionally, only a small percentage of
these alleles are full-length, making it impossible to use the known sequence for
reagent development. To address this, we developed a fast, high-throughput method
to discover full-length MHC-II alleles and used it to characterize alleles in 32
pig-tailed macaques. By this method, we identified 128 total alleles across all
six loci. We also performed an exon 2-based genotyping assay to validate the full
length sequencing results; this genotyping assay could be optimized for use in
determining MHC-II allele frequencies in large cohorts of pig-tailed macaques.
PMID- 25129473
TI - Pericardial effusion following transcatheter aortic valve implantation:
echocardiography and multi-detector row computed tomography evaluation.
AB - Although pericardial effusion (PE) early after transcatheter aortic valve
implantation (TAVI) has been reported in few registries, late PE at follow-up
remains unexplored. Particularly, after transapical TAVI, diagnosis of PE with
transthoracic echocardiography (TTE) may be challenging. The present evaluation
assessed the incidence of PE early after TAVI and at 1 month follow-up using TTE
and multi-detector computed tomography (MDCT). The agreement between TTE and MDCT
to diagnose the presence and severity of PE at 1 month follow-up was evaluated.
Overall 293 patients undergoing TAVI were included. Pre-discharge TTE was
performed in all patients. At 1 month, repeat TTE was performed in 234 patients
and additional MDCT evaluation in 143 patients. Pre-discharge small and moderate
PE was observed in 74.1 and 4.1 % of patients, respectively, whereas significant
PE was diagnosed in 8 (2.7 %) patients without differences between procedural
access: 1.6 versus 3.6 % for transfemoral and transapical respectively, p =
0.474. At 1 month new-onset moderate PE was noted in 6 (2.5 %) patients all of
who underwent transapical TAVI. MDCT and TTE disagreed on the grade of PE in 38
patients. Importantly, one patient with small PE on TTE was considered having
moderate PE and two patients with small and moderate PE were considered having
large PE. Also, two patients with moderate PE on echocardiography were considered
small PE on MDCT. In conclusions, significant PE early after TAVI is infrequent.
The prevalence of small and moderate PE remains stable at 1 month follow-up. MDCT
refines the diagnosis of significant PE.
PMID- 25129476
TI - A light initiated chemiluminescent immunoassay for procalcitonin.
PMID- 25129474
TI - Associated factors with antipsychotic use in long-term institutional care in
eight European countries: Results from the RightTimePlaceCare study.
AB - OBJECTIVES: To determine factors associated with the antipsychotic (AP)
prescription for people with dementia (PwD) recently admitted to institutional
long-term care facilities (LTCFs) and to ascertain differences in the use of this
medication in 8 European countries. DESIGN: An exploratory cross-sectional study.
SETTING: LTCFs from 8 European countries (Estonia, Finland, France, Germany, The
Netherlands, Spain, Sweden, and England). PARTICIPANTS: A total of 791 PwD
recently admitted to an LTCF and their caregivers. MEASUREMENTS: Baseline data
from RightTimePlaceCare survey was used. Patients' medical conditions,
neuropsychiatric symptoms, physical and cognitive status, and medications were
recorded. Multiple logistic regression models were used to assess associations
with the AP use. RESULTS: A group of 296 patients (37.4%) of 791 patients
recently admitted received AP medication. The prevalence of the use of 1 or more
APs varied between study countries, ranging from 12% in Sweden to 54% in Spain.
Factors independently associated with the AP use were living in Sweden [odds
ratio (OR) 0.12, 95% confidence interval (CI) 0.05-0.30], Finland (OR 0.26, 95%
CI 0.14-0.48), Germany (OR 2.75, 95% CI 1.55-4.86) and Estonia (OR 6.79, 95% CI
3.84-12.0). The odds of AP use decreased with the presence of a dementia specific
unit in the LTCF (OR 0.60, 95% CI 0.39-0.92), but was higher among residents with
a hyperactivity behavior (OR 2.12, 95% CI 1.41-3.18). CONCLUSION: The current
study shows that more than one-third of the residents recently admitted received
APs and that prescription frequency across countries varied significantly. This
study raises the possibility that the presence of a dementia-specific unit might
play a role in the AP use. Further studies should investigate this association
and seek better understanding of what will achieve optimal quality of AP use
among newly admitted residents in LTCF.
PMID- 25129475
TI - Perioperative changes in pro and anticoagulant factors in prostate cancer
patients undergoing laparoscopic and robotic radical prostatectomy with different
anaesthetic techniques.
AB - BACKGROUND: Laparoscopic prostatectomy (LRP) may activate clotting system
influencing the risk of perioperative thrombosis in patients with prostate
cancer. Moreover, different anaesthetic techniques can also modify coagulant
factors. Thus, the aim of this study was to investigate the effects on pro- and
anti-coagulant and fibrinolytic factors of two established types of anaesthesia
in patients with prostate cancer undergoing elective LRP. METHODS: 102 patients
with primary prostate cancer, who underwent conventional LRP or robot-assisted
laparoscopic prostatectomy (RALP), were studied and divided into 2 groups to
receive total intravenous anesthesia with target-controlled infusion (TIVA-TCI)
or balanced inhalation anaesthesia (BAL) prior to surgery. Before the induction
of anaesthesia (T0), 1 hr (T1) and 24 hrs post-surgery (T2), some pro-coagulant
factors, fibronolysis markers, p-selectin and haemostatic system inhibitors were
evaluated. RESULTS: Both TIVA-TCI and BAL patients showed a marked and
significant increase in pro-coagulant factors and consequent reduction in
haemostatic system inhibitors in the early post operative period (p <= 0.004 for
each markers). Use of RALP showed a significant increase in prothrombotic markers
as compared to LRP. In TIVA patients undergoing LRP, a significant reduction of p
selectin levels between T0 and T2 (p = 0.001) was observed as compared to BAL,
suggesting a better protective effect on platelet activation of anaesthetic
agents used for TIVA. CONCLUSIONS: Both anaesthetic techniques significantly seem
to increase the risk of thrombosis in prostate cancer patients undergoing LRP,
mainly when the robotic device was utilized, encouraging the use of a peri
operative thromboembolic prophylaxis in these patients.
PMID- 25129477
TI - Role of Fas/FasL signaling in regulation of anti-viral response during HSV-2
vaginal infection in mice.
AB - Fas receptor-Fas ligand (FasL) signaling is involved in apoptosis of virus
infected cells but increasing evidence accumulates on Fas receptor as a mediator
of apoptosis-independent processes such as induction of activating and pro
inflammatory signals. In this study, we examined the role of Fas/FasL pathway in
regulation of anti-viral response to genital HSV-2 infection using a murine model
of HSV-2 infection applied to C57BL6/J, B6. MRL-Faslpr/J and B6Smn.C3-Faslgld/J
mice. HSV-2 infection of Fas- and FasL-deficient mice led to decreased migration
of IFN-gamma expressing NK cells and CD4+ T cells, but not of gammadelta T cells,
into the vaginal tissue. The vaginal tissues of HSV-2 infected Fas- and FasL
deficient mice showed increased production of IL-10, followed by low expression
of the early CD69 activation marker on CD4+ and CD8+ T cells and increased
numbers of regulatory T cells (Tregs). Experiments in co-cultures of CD4+ T cells
and bone marrow derived dendritic cells showed that lack of bilateral Fas-FasL
signaling led to expansion of Tregs and increased production of IL-10 and TGF
beta1. Our results demonstrate that Fas/FasL can regulate development of
tolerogenic dendritic cells and expansion of Tregs early during HSV-2 infection,
which further influences effective anti-viral response.
PMID- 25129478
TI - Modulatory role of vitamin A on the Candida albicans-induced immune response in
human monocytes.
AB - Beyond its well-documented role in reproduction, embryogenesis and maintenance of
body tissues, vitamin A has attracted considerable attention due to its
immunomodulatory effects on both the innate and the adaptive immune responses. In
infectious diseases, vitamin A has been shown to have a host-protective effect in
infections of bacterial, viral or protozoan origin. Nevertheless, its impact in
fungal infections remains unknown. Meanwhile, the frequency of invasive mycoses
keeps on growing, with Candida albicans being the major opportunistic fungal
pathogen and associated with high mortality. In the present work, we explored the
impact of all-trans retinoic acid (atRA), the most active metabolite of vitamin
A, on the innate immune response against C. albicans in human monocytes. Our
results show a strong immunomodulatory role for atRA, leading to a significant
down-regulation of the fungi-induced expression and secretion of the pro
inflammatory cytokines TNFalpha, IL6 and IL12. Moreover, atRA significantly
suppressed the expression of Dectin-1, a major fungal pattern recognition
receptor, as well as the Dectin-1-dependent cytokine production. Both RAR
dependent and RAR-independent mechanisms seem to play a role in the atRA-mediated
immunomodulation. Our findings open a new direction to elucidate the role of
vitamin A on the immune function during fungal infections.
PMID- 25129479
TI - CAPON-nNOS coupling can serve as a target for developing new anxiolytics.
AB - Anxiety disorders are highly prevalent psychiatric diseases. There is need for a
deeper understanding of anxiety control mechanisms in the mammalian brain and for
development of new anxiolytic agents. Here we report that the coupling between
neuronal nitric oxide synthase (nNOS) and its carboxy-terminal PDZ ligand (CAPON)
can serve as a target for developing new anxiolytic agents. Augmenting nNOS-CAPON
interaction in the hippocampus of mice by overexpressing full-length CAPON gave
rise to anxiogenic-like behaviors, whereas dissociating CAPON from nNOS by
overexpressing CAPON-125C or CAPON-20C (the C-terminal 125 or 20 amino acids of
CAPON) or delivering Tat-CAPON-12C (a peptide comprising Tat and the 12 C
terminal amino acids of CAPON) in the hippocampus of mice produced anxiolytic
like effects. Mice subjected to chronic mild stress (CMS) displayed a substantial
increase in nNOS-CAPON coupling in the hippocampus and a consequent anxiogenic
like phenotype. Disrupting nNOS-CAPON coupling reversed the CMS-induced
anxiogenic-like behaviors. Moreover, small-molecule blockers of nNOS-CAPON
binding rapidly produced anxiolytic-like effects. Dexamethasone-induced ras
protein 1 (Dexras1)-extracellular signal-regulated kinase (ERK) signaling was
involved in the behavioral effects of nNOS-CAPON association. Thus, nNOS-CAPON
association contributes to the modulation of anxiety-related behaviors via
regulating Dexras1-ERK signaling and can serve as a target for developing
potential anxiolytics.
PMID- 25129480
TI - In vivo proteomic imaging analysis of caveolae reveals pumping system to
penetrate solid tumors.
AB - Technologies are needed to map and image biological barriers in vivo that limit
solid tumor delivery and, ultimately, the effectiveness of imaging and
therapeutic agents. Here we integrate proteomic and imaging analyses of caveolae
at the blood-tumor interface to discover an active transendothelial portal to
infiltrate tumors. A post-translationally modified form of annexin A1 (AnnA1) is
selectively concentrated in human and rodent tumor caveolae. To follow
trafficking, we generated a specific AnnA1 antibody that targets caveolae in the
tumor endothelium. Intravital microscopy of caveolae-immunotargeted fluorophores
even at low intravenous doses showed rapid and robust pumping across the
endothelium to enter mammary, prostate and lung tumors. Within 1 h, the
fluorescence signal concentrated throughout tumors to exceed the peak levels in
blood. This transvascular pumping required the expression of caveolin 1 and
annexin A1. Tumor uptake with other antibodies were >100-fold less. This
proteomic imaging strategy reveals a unique target, antibody and caveolae pumping
system for solid tumor penetration.
PMID- 25129482
TI - IGRA as a predictive factor of silent pulmonary changes in individuals following
exposure to tuberculosis.
AB - OBJECTIVES: We conducted a study on usefulness of the tuberculin skin test (TST)
and the Quantiferon-TB Gold IT (QFT) tests as predictors of radiological changes
after contact with tuberculosis. MATERIALS AND METHODS: The study group consisted
of TB-exposed HCWs working in the Military Institute of Medicine (Warsaw,
Poland). The usefulness of TST, QFT, and a combination of both tests was assessed
for prediction of silent radiological findings. RESULTS: 83 previously TB-exposed
participants were recruited. None of the participants had a history of active
tuberculosis. Positive TST results were reported in 72 (86.8 %) participants, and
positive QFTs were observed in 27 (32.5 %) cases. Chest radiographs revealed 23
findings specific for non-active tuberculosis in 18 (21.7 %) participants. The
results of the QFTs were associated with the highest negative predictive value,
positive predictive value, and positive likelihood ratio of silent chest X-ray
findings suggestive of latent tuberculosis infection. Positive QFT was the only
statistically significant variable that increases the odds ratio (OR-8.3) of the
presence of typical of tuberculosis radiological changes in the lung. CONCLUSION:
A positive QFT result in an individual with no TB history who was exposed to
tuberculosis in the past is associated with a significantly higher risk of
clinically silent parenchymal lesions in lungs suggestive of previous
tuberculosis.
PMID- 25129481
TI - Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK
inhibition.
AB - Alopecia areata (AA) is a common autoimmune disease resulting from damage of the
hair follicle by T cells. The immune pathways required for autoreactive T cell
activation in AA are not defined limiting clinical development of rational
targeted therapies. Genome-wide association studies (GWAS) implicated ligands for
the NKG2D receptor (product of the KLRK1 gene) in disease pathogenesis. Here, we
show that cytotoxic CD8(+)NKG2D(+) T cells are both necessary and sufficient for
the induction of AA in mouse models of disease. Global transcriptional profiling
of mouse and human AA skin revealed gene expression signatures indicative of
cytotoxic T cell infiltration, an interferon-gamma (IFN-gamma) response and
upregulation of several gamma-chain (gammac) cytokines known to promote the
activation and survival of IFN-gamma-producing CD8(+)NKG2D(+) effector T cells.
Therapeutically, antibody-mediated blockade of IFN-gamma, interleukin-2 (IL-2) or
interleukin-15 receptor beta (IL-15Rbeta) prevented disease development, reducing
the accumulation of CD8(+)NKG2D(+) T cells in the skin and the dermal IFN
response in a mouse model of AA. Systemically administered pharmacological
inhibitors of Janus kinase (JAK) family protein tyrosine kinases, downstream
effectors of the IFN-gamma and gammac cytokine receptors, eliminated the IFN
signature and prevented the development of AA, while topical administration
promoted hair regrowth and reversed established disease. Notably, three patients
treated with oral ruxolitinib, an inhibitor of JAK1 and JAK2, achieved near
complete hair regrowth within 5 months of treatment, suggesting the potential
clinical utility of JAK inhibition in human AA.
PMID- 25129483
TI - A QM/MM study of the associative mechanism for the phosphorylation reaction
catalyzed by protein kinase A and its D166A mutant.
AB - Here we analyze in detail the possible catalytic role of the associative
mechanism in the gamma-phosphoryl transfer reaction in the catalytic subunit of
the mammalian cyclic AMP-dependent protein kinase (PKA) enzyme and its D166A
mutant. We have used a complete solvated model of the ATP-Mg2-Kemptide/PKA system
and good levels of theory (B3LYP/MM and MP2/MM) to determine several potential
energy paths from different MD snapshots, and we present a deep analysis of the
interaction distances and energies between ligands, metals and enzyme residues.
We have also tested the electrostatic stabilization of the transition state
structures localized herein with the charge balance hypothesis. Overall, the
results obtained in this work reopen the discussion about the plausibility of the
associative reaction pathway and highlight the proposed role of the catalytic
triad Asp166-Lys168-Thr201.
PMID- 25129484
TI - Exploring the dynamics and interaction of a full ErbB2 receptor and Trastuzumab
Fab antibody in a lipid bilayer model using Martini coarse-grained force field.
AB - Coarse grained (CG) modeling has been applied to study the influence of the
Trastuzumab monoclonal antibody on the structure and dynamics of the full ErbB2
receptor dimer, including the lipid bilayer. The usage of CG models to study such
complexes is almost mandatory, at present, due to the large size of the whole
system. We will show that the Martini model performs satisfactorily well, giving
results well-matched with those obtained by atomistic models as well as with the
experimental information existing on homolog receptors. For example, the extra
and intracellular domains approach the bilayer surface in both the monomer and
dimer cases. The Trastuzumab-Fab hinders the interaction of the receptors with
the lipid bilayer. Another interesting effect of the antibody is the disruption
of the antiparallel arrangement of the juxtamembrane segments in the dimer case.
These findings might help to understand the effect of the antibody on the
receptor bioactivity.
PMID- 25129485
TI - Buttressing the staple line: a randomized comparison between staple-line
reinforcement versus no reinforcement during sleeve gastrectomy.
AB - Bariatric surgery is recommended for Indian patients with body mass index (BMI)
>32.5 kg/m(2) with at least one comorbidity and >37.5 kg/m(2) without a
comorbidity. In laparoscopic sleeve gastrectomy, bleeding and leakage from the
staple line are common post-operative events. Peri-Strips Dry(r) with Veritas(r)
(PSD-V) is used in staple-line reinforcement. This was a single-investigator,
multicenter, randomized study of 100 patients undergoing standard sleeve
gastrectomy with a 34 or 36 French bougie. Patients were randomized 1:1 to PSD-V
or control groups; no buttress material was used in the control group. The
primary objective was to assess complication rates (any staple-line bleed or leak
from the intra-operative visit through day 30) associated with sleeve
gastrectomy. Surgical time (from first incision to closure of last incision) and
the number of clips and/or sutures used to control bleeding were also assessed.
Fewer staple-line bleeds were observed in the PSD-V group than the control group
(23/51 [45.1 %] vs 39/49 [79.6 %] patients; p=0.0005), and the bleeding was of a
lower severity (p=0.0002). No staple-line leaks were observed. Surgical time was
shorter in patients who received PSD-V (58.8 vs 72.8 min; p=0.0153), and fewer
patients required hemostatic clips and/or sutures (10/51 [19.6 %] vs 33/49 [67.3
%] patients; p<0.0001). Fewer patients in the PSD-V than the control group
experienced adverse events (2/51 [3.9 %] vs 5/49 [10.2 %] patients). The use of
PSD-V reduced the incidence and severity of staple-line bleeding and was
associated with a reduction in surgical time compared with no staple-line
reinforcement.
PMID- 25129486
TI - An update on United States asthma centers: 2013.
PMID- 25129487
TI - Prevalence and determinants of atopy and allergic diseases among school-age
children in rural Saskatchewan, Canada.
AB - BACKGROUND: There have been few investigations of farming-related activities or
specific characteristics resulting in the associations between those exposures
and atopic disease. OBJECTIVE: To study the associations between farm-associated
exposures and atopic diseases. METHODS: As part of a longitudinal study of lung
health in rural residents, a cross-sectional baseline study was conducted in
rural Saskatchewan, Canada. This included an initial survey phase followed by a
clinical testing phase. A subsample of 584 children (grades 1-8) completed skin
prick testing to assess atopic status. Atopy was defined as a positive reaction
to any of 6 allergens (local grasses, wheat dust, cat dander, house dust mite,
Alternaria species, or Cladosporium species) of at least 3 mm compared with the
negative control. RESULTS: Of those who completed clinical testing, the
prevalence of atopy was 19.4%, that of hay fever was 8.8%, and that of eczema was
27.4%. Based on skin prick testing, sensitization was highest for cat dander
(8.6%) followed by local grasses (8.2%) and house dust mite (5.1%). After
adjustment for potential confounders, home location (farm vs non-farm) was not
associated with atopic status. However, livestock farming was protective against
atopy (adjusted odds ratio 0.38, 95% confidence interval 0.17-0.88). In contrast,
current residence on a farm was associated with an increase in the likelihood of
hay fever in these children (adjusted odds ratio 3.68, 95% confidence interval
1.29-10.45). Also, regular farming activities in the past year were associated
with an increased risk of hay fever. CONCLUSION: In children, livestock exposure
has a protective effect on skin prick test positivity, whereas farm living and
activities increase the risk of hay fever.
PMID- 25129488
TI - Exploring the link between ceramide and ionizing radiation.
AB - The aim of radiotherapy is to eradicate cancer cells with ionizing radiation;
tumor cell death following irradiation can be induced by several signaling
pathways, most of which are triggered as a consequence of DNA damage, the primary
and major relevant cell response to radiation. Several lines of evidence
demonstrated that ceramide, a crucial sensor and/or effector of different
signalling pathways promoting cell cycle arrest, death and differentiation, is
directly involved in the molecular mechanisms underlying cellular response to
irradiation. Most of the studies strongly support a direct relationship between
ceramide accumulation and radiation-induced cell death, mainly apoptosis; for
this reason, defining the contribution of the multiple metabolic pathways leading
to ceramide formation and the causes of its dysregulated metabolism represent the
main goal in order to elucidate the ceramide-mediated signaling in radiotherapy.
In this review, we summarize the current knowledge concerning the different
routes leading to ceramide accumulation in radiation-induced cell response with
particular regard to the role of the enzymes involved in both ceramide neogenesis
and catabolism. Emphasis is placed on sphingolipid breakdown as mechanism of
ceramide generation activated following cell irradiation; the functional
relevance of this pathway, and the role of glycosphingolipid glycohydrolases as
direct targets of ionizing radiation are also discussed. These new findings add a
further attractive point of investigation to better define the complex interplay
between sphingolipid metabolism and radiation therapy.
PMID- 25129489
TI - Long term survival in a case of concurrent retroperitoneal liposarcoma and renal
cell carcinoma: a case report.
AB - BACKGROUND: Liposarcoma is one of the most common soft tissue sarcomas found in
adults. It has a predilection for retroperitoneal space. Renal cell carcinoma is
the most common tumor of the kidney. CASE PRESENTATION: Concurrent
retroperitoneal liposarcoma and renal cell carcinoma were found in a 34-year-old
Japanese man. The renal tumor was first detected by ultrasonography, it was
confirmed by computed tomography, which also identified a presumptive
retroperitoneal liposarcoma, and the tumors were further assessed with magnetic
resonance imaging. The patient was treated by surgical resection of
retroperitoneal liposarcoma and left nephrectomy and has been disease-free for 10
years. CONCLUSIONS: The concomitant occurrence of a renal tumor and a primary
primary liposarcoma is rare. The major factors promoting a good prognosis in this
case were the favorable histology and the small size of the tumors.
PMID- 25129491
TI - A pilot study of S-1-based concurrent chemoradiotherapy in patients with biliary
tract cancer.
AB - PURPOSE: S-1 chemotherapy is effective against advanced biliary tract cancer. The
purpose was to evaluate the efficacy and safety of S-1-based concurrent
chemoradiotherapy in patients with advanced biliary tract cancer. METHODS:
Patients with pathologically-proven advanced biliary tract cancer were eligible.
S-1 was orally administered at a dose of 40 mg/m(2), twice daily from day 1 to 14
and from day 22 to 35; concurrent radiotherapy of 180-200 cGy per fraction was
delivered in 25-28 fractions. After treatment completion, tumor response was
evaluated by computed tomography. In the first stage of the optimal two-stage
phase II design, 18 patients were required. RESULTS: Twenty patients were
enrolled between August 2006 and February 2009. The median age was 62.5 years
(range 45-77 years). The median follow-up time was 11.6 months (range 1.9-49.1
months). Fifteen patients (75%) had extrahepatic cholangiocarcinoma, two patients
(10%) had intrahepatic cholangiocarcinoma, and three patients (15%) had
gallbladder cancer. After treatment, a partial response was achieved in three
patients (15%), and stable disease was achieved in 14 patients (70%). The overall
response rate was 15%, and the disease stabilization rate was 85%. There was no
grade 4 toxicity or treatment-related death. The common grade 3 toxicities were
thrombocytopenia (15%), neutropenia (10%), and nausea (10%). The median
progression-free survival and median overall survival were 5.9 months (range 2.2
9.5 months) and 10.8 months (range 1.1-20.4 months), respectively. CONCLUSIONS:
This study shows that S-1-based concurrent chemoradiotherapy is feasible and
tolerable in patients with advanced biliary tract cancer. It will be further
confirmed in a following large-scale phase II study.
PMID- 25129492
TI - Utilization of roughages and concentrates relative to that of milk replacer
increases strongly with age in veal calves.
AB - We aimed to investigate the feeding values of milk replacer (MR), roughage, and
concentrates for veal calves in a paired-gain setting, thus avoiding any prior
assumptions in feeding values and major differences in nutrient intakes. One
hundred sixty male Holstein-Friesian calves at 2 wk of age and 45 +/- 0.2 kg of
body weight (BW) were included in the experiment. Calves were allocated to pens
(5 calves per pen) and pens were randomly assigned to 1 of 4 solid feed (SF)
levels: SF1, SF2, SF3, or SF4, respectively, and to 1 of 2 roughage-to
concentrate (R:C) ratios: 20:80 or 50:50. An adaptation period from wk 1 to 10
preceded the experimental period (wk 11 to 27). Total dry matter (DM) intake from
SF was targeted to reach 20, 100, 180, and 260 kg of DM for SF1 to SF4,
respectively, during the 16-wk experimental period, and increased with
preplanned, equal weekly increments. Roughage was composed of 50% corn silage and
50% chopped wheat straw based on DM. The quantity of MR provided was adjusted
every 2 wk based on BW to achieve similar targeted rates of carcass gain across
treatments. The reduction in MR provided (in kg of DM) to realize equal rates of
carcass gain with inclusion of SF (in kg of DM) differed between the R:C ratio of
50:50 (0.41 kg of MR/kg of SF) and the R:C ratio of 20:80 (0.52 kg of MR/kg of
SF). As carcass gain unintentionally increased with SF intake, the paired-gain
objective was not fully achieved. When adjusted for realized rates of carcass
gain, calves fed an R:C ratio of 20:80 still required 10% less MR than calves fed
an R:C ratio of 50:50 for equal rates of carcass gain, indicating that the
utilization of SF for gain increased with concentrate inclusion. Averaged for the
16-wk experimental period, the feeding value of MR relative to that of
concentrates and roughages was close to that predicted based on their respective
digestible energy contents. Nevertheless, the feeding value of SF relative to
that of MR increased substantially with age. Therefore, additivity in feeding
values of these ration components cannot be assumed. The results of the current
study may contribute to the development of new concepts for formulation of veal
calf diets with substantial amounts of SF.
PMID- 25129493
TI - Short communication: Added value of rumination time for the prediction of dry
matter intake in lactating dairy cows.
AB - The objective of the current study was to quantify the change in the prediction
of dry matter intake (DMI) resulting from the inclusion of rumination time (RT)
in the 2001 National Research Council (NRC) DMI prediction model. Forty-one
Holstein cows fed the same total mixed ration were involved in a 10-wk study.
Individual DMI were measured daily. The accuracy and precision of the original
NRC prediction model, based on body weight, fat-corrected milk, and week of
lactation as independent variables, was compared with the accuracy and precision
of the same model with RT as an additional independent variable. The RT estimate
was significant in the model developed but had a low value (0.031 kg/h). Root
mean square prediction errors were very similar in the 2 models (1.70 and 1.68
kg/d) as were the other indicators (R(2), linear bias, random error, and
concordance correlation coefficient) selected to compare the models in this
study. These results indicate no gain in DMI prediction precision or accuracy
when RT is included in the NRC model.
PMID- 25129494
TI - Factors affecting life cycle assessment of milk produced on 6 Mediterranean
buffalo farms.
AB - This study quantifies the environmental impact of milk production of Italian
Mediterranean buffaloes and points out the farm characteristics that mainly
affect their environmental performance. Life cycle assessment was applied in a
sample of 6 farms. The functional unit was 1 kg of normalized buffalo milk (LBN),
with a reference milk fat and protein content of 8.3 and 4.73%, respectively. The
system boundaries included the agricultural phase of the buffalo milk chain from
cradle to farm gate. An economic criterion was adopted to allocate the impacts on
milk production. Impact categories investigated were global warming (GW), abiotic
depletion (AD), photochemical ozone formation (PO), acidification (AC), and
eutrophication (EU). The contribution to the total results of the following farm
activities were investigated: (1) on-farm energy consumption, (2) manure
management, (3) manure application, (4) on-farm feed production (comprising
production and application of chemical fertilizers and pesticides), (5) purchased
feed production, (6) enteric fermentation, and (7) transport of purchased feeds,
chemical fertilizers, and pesticides from producers to farms. Global warming
associated with 1 kg of LBN resulted in 5.07 kg of CO2 Eq [coefficient of
variation (CV)=21.9%], AD was 3.5 * 10(-3) kg of Sb Eq (CV=51.7%), PO was 6.8 *
10(-4) kg of C2H4 Eq (CV=28.8%), AC was 6.5 * 10(-2) kg of SO2 Eq (CV=30.3%), and
EU was 3.3 * 10(-2) kg of PO4(3-) Eq (CV=36.5%). The contribution of enteric
fermentation and manure application to GW is 37 and 20%, respectively; on-farm
consumption, on-farm feed production, and purchased feed production are the main
contributors to AD; about 70% of PO is due to enteric fermentation; manure
management and manure application are responsible for 55 and 25% of AC and 25 and
55% of EU, respectively. Methane and N2O are responsible for 44 and 43% of GW,
respectively. Crude oil consumption is responsible for about 72% of AD;
contribution of CH4 to PO is 77%; NH3 is the main contributor to AC (92%); NO3(-)
and NH3 are responsible for 55 and 41% of EU, respectively; contribution of P to
EU is only 3.2%. The main characteristics explaining the significant variability
of life cycle assessment are milk productivity and amount of purchased feed per
kilogram of LBN. Improvement of LBN production per buffalo cow is the main
strategy for reducing GW and PO; improvement of the efficiency of feed use is the
strategy proposed for mitigating AD, PO, AC, and EU.
PMID- 25129490
TI - Biological Modulators in Eosinophilic Diseases.
AB - Eosinophils can regulate local and systemic inflammation, and their presence in
higher numbers appears to play an important role in the pathology of various
atopic and inflammatory diseases. Eosinophil maturation, recruitment, and
survival depend on several cytokine regulators, including interleukin (IL)-5, IL
4, and IL-13 as well as growth factors such as GM-CSF. Over the last decade, the
approach to treating eosinophilic diseases has changed greatly. A number of
biologic modulators have been developed to target eosinophilic inflammatory
pathways, and their usage has resulted in variable clinical improvement in the
treatment of eosinophilic-associated conditions. Novel targeted therapies that
are safe and effective for treating these disorders are being investigated. This
review summarizes the clinical use of biologic agents that have been studied in
clinical trials or approved for treating eosinophilic diseases.
PMID- 25129495
TI - Comparison of genomic predictions using genomic relationship matrices built with
different weighting factors to account for locus-specific variances.
AB - Various models have been used for genomic prediction. Bayesian variable selection
models often predict more accurate genomic breeding values than genomic BLUP
(GBLUP), but GBLUP is generally preferred for routine genomic evaluations because
of low computational demand. The objective of this study was to achieve the
benefits of both models using results from Bayesian models and genome-wide
association studies as weights on single nucleotide polymorphism (SNP) markers
when constructing the genomic matrix (G-matrix) for genomic prediction. The data
comprised 5,221 progeny-tested bulls from the Nordic Holstein population. The
animals were genotyped using the Illumina Bovine SNP50 BeadChip (Illumina Inc.,
San Diego, CA). Weighting factors in this investigation were the posterior SNP
variance, the square of the posterior SNP effect, and the corresponding minus
base-10 logarithm of the marker association P-value [-log10(P)] of a t-test
obtained from the analysis using a Bayesian mixture model with 4 normal
distributions, the square of the estimated SNP effect, and the corresponding
log10(P) of a t-test obtained from the analysis using a classical genome-wide
association study model (linear regression model). The weights were derived from
the analysis based on data sets that were 0, 1, 3, or 5 yr before performing
genomic prediction. In building a G-matrix, the weights were assigned either to
each marker (single-marker weighting) or to each group of approximately 5 to 150
markers (group-marker weighting). The analysis was carried out for milk yield,
fat yield, protein yield, fertility, and mastitis. Deregressed proofs (DRP) were
used as response variables to predict genomic estimated breeding values (GEBV).
Averaging over the 5 traits, the Bayesian model led to 2.0% higher reliability of
GEBV than the GBLUP model with an original unweighted G-matrix. The superiority
of using a GBLUP with weighted G-matrix over GBLUP with an original unweighted G
matrix was the largest when using a weighting factor of posterior variance,
resulting in 1.7 percentage points higher reliability. The second best weighting
factors were -log10 (P-value) of a t-test corresponding to the square of the
posterior SNP effect from the Bayesian model and -log10 (P-value) of a t-test
corresponding to the square of the estimated SNP effect from the linear
regression model, followed by the square of estimated SNP effect and the square
of the posterior SNP effect. In addition, group-marker weighting performed better
than single-marker weighting in terms of reducing bias of GEBV, and also slightly
increased prediction reliability. The differences between weighting factors and
scenarios were larger in prediction bias than in prediction accuracy. Finally,
weights derived from a data set having a lag up to 3 yr did not reduce
reliability of GEBV. The results indicate that posterior SNP variance estimated
from a Bayesian mixture model is a good alternative weighting factor, and common
weights on group markers with a size of 30 markers is a good strategy when using
markers of the 50,000-marker (50K) chip. In a population with gradually
increasing reference data, the weights can be updated once every 3 yr.
PMID- 25129497
TI - In vitro susceptibility of bovine mastitis pathogens to a combination of
penicillin and framycetin: development of interpretive criteria for testing by
broth microdilution and disk diffusion.
AB - Dry cow therapy is an important part of mastitis control. This therapy typically
consists of an antibiotic or antibiotics administered at a single dose by
intramammary infusion at dry off to treat or prevent infection by prevalent
mastitis pathogens. A combination dry cow therapy consisting of the active
components penicillin and framycetin is currently used in several countries.
Despite its use, standardized methods for the susceptibility testing of this
combination against mastitis pathogens have not been established. In this study,
which used Clinical and Laboratory Standards Institute methodology, preliminary
interpretive criteria for the broth microdilution minimum inhibitory
concentration (MIC) testing of mastitis pathogens to penicillin combined with
framycetin (2:1 wt/wt) were established based on the amount of drug achieved and
maintained postadministration in the udder. Based on resulting MIC distributions
of recent veterinary field isolates and a subset of isolates preselected for
resistance to beta-lactams or aminoglycosides and concentrations achieved
postadministration, criteria for broth microdilution testing of the combination
(susceptible, intermediate, resistant in micrograms per milliliter) were set as
follows: Escherichia coli <=8/4, 16/8, >=32/16; Staphylococcus spp. <=2/1, 4/2
8/4, >16/8; Streptococcus uberis and Streptococcus dysgalactiae <0.25/0.12,
0.5/0.25-2/1, >4/2. A disk diffusion test using disks containing 100 MUg of
framycetin and 10 IU of penicillin was also developed, and preliminary
interpretive criteria (susceptible, intermediate, resistant in millimeters) were
set based on correlation to broth MIC values and the minimization of interpretive
errors between isolates tested concurrently by broth microdilution and disk
diffusion as follows: E. coli >=18, 16-17, <=15; Staphylococcus spp. >=21, 18-20,
<=17; Strep. uberis and Strep. dysgalactiae >=21, 19-20, <=18. In addition,
ranges for the quality control of the testing of this combination by both broth
microdilution and disk diffusion are provided. Based on these criteria and recent
veterinary mastitis isolates, 96.0/96.8% of E. coli, 93.7/89.1% of Staph. aureus,
94.6/96.4% coagulase-negative staphylococci, 94.5/97.0% of Strep. uberis, and
96.7/100.0% Strep. dysgalactiae were susceptible to the combination by broth
microdilution or disk diffusion, respectively. The availability of these methods
will allow for the susceptibility testing of clinical isolates in the field and
will also provide a way to monitor for resistance development as this combination
is used going forward.
PMID- 25129496
TI - Enumeration of clostridia in goat milk using an optimized membrane filtration
technique.
AB - A membrane filtration technique developed for counting butyric acid bacteria in
cow milk was further developed for analysis of goat milk. Reduction of the sample
volume, prolongation of incubation time after addition of proteolytic enzyme and
detergent, and a novel step of ultrasonic treatment during incubation allowed
filtration of goat milk even in the case of somatic cell counts (SCC) exceeding
10(6)/mL. However, filterability was impaired in milk from goats in late
lactation. In total, spore counts were assessed in 329 farm bulk goat milk
samples. Membrane filtration technique counts were lower than numbers revealed by
the classic most probable number technique. Thus, method-specific thresholds for
milk to evaluate the risk of late blowing have to be set. As expected, the spore
counts of milk samples from suppliers not feeding silage were significantly lower
than the spore counts of milk samples from suppliers using silage feeds. Not only
were counts different, the clostridial spore population also varied
significantly. By using 16S rRNA gene PCR and gene sequencing, 342 strains from
15 clostridial species were identified. The most common Clostridium species were
Clostridium tyrobutyricum (40.4%), Clostridium sporogenes (38.3%), Clostridium
bifermentans (7.6%), and Clostridium perfringens (5.3%). The 2 most frequently
occurring species C. tyrobutyricum and C. sporogenes accounted for 84.7% of the
isolates derived from samples of suppliers feeding silage (n=288). In contrast,
in samples from suppliers without silage feeding (n=55), these species were
detected in only 45.5% of the isolates.
PMID- 25129498
TI - Methane emissions among individual dairy cows during milking quantified by
eructation peaks or ratio with carbon dioxide.
AB - The aims of this study were to compare methods for examining measurements of CH4
and CO2 emissions of dairy cows during milking and to assess repeatability and
variation of CH4 emissions among individual dairy cows. Measurements of CH4 and
CO2 emissions from 36 cows were collected in 3 consecutive feeding periods. In
the first period, cows were fed a commercial partial mixed ration (PMR)
containing 69% forage. In the second and third periods, the same 36 cows were fed
a high-forage PMR ration containing 75% forage, with either a high grass silage
or high maize silage content. Emissions of CH4 during each milking were examined
using 2 methods. First, peaks in CH4 concentration due to eructations during
milking were quantified. Second, ratios of CH4 and CO2 average concentrations
during milking were calculated. A linear mixed model was used to assess
differences between PMR. Variation in CH4 emissions was observed among cows after
adjusting for effects of lactation number, week of lactation, diet, individual
cow, and feeding period, with coefficients of variation estimated from variance
components ranging from 11 to 14% across diets and methods of quantifying
emissions. No significant difference was detected between the 3 PMR in CH4
emissions estimated by either method. Emissions of CH4 calculated from eructation
peaks or as CH4 to CO2 ratio were positively associated with forage dry matter
intake. Ranking of cows according to CH4 emissions on different diets was
correlated for both methods, although rank correlations and repeatability were
greater for CH4 concentration from eructation peaks than for CH4-to-CO2 ratio. We
conclude that quantifying enteric CH4 emissions either using eructation peaks in
concentration or as CH4-to-CO2 ratio can provide highly repeatable phenotypes for
ranking cows on CH4 output.
PMID- 25129499
TI - A pregnancy detection assay using milk samples: evaluation and considerations.
AB - Two experiments were conducted to evaluate a pregnancy-detection assay based on
the measurement of pregnancy-associated glycoproteins (PAG) in milk samples. In
experiment 1, milk samples were collected on the day of first pregnancy check (33
52 d postinsemination; n=119) or second check (60-74 d postinsemination; n=60).
The accuracy in identification of pregnant and nonpregnant cows was 99% at first
check. Only 6% of samples were found to be within an intermediate range of PAG
concentrations and classified as requiring recheck by the assay. At second check,
the accuracy of the assay was 98%. Fifteen percent of these samples were
classified as requiring recheck. In experiments 2a (n=17 cows) and 2b (n=16
cows), milk and plasma samples were collected from cows at weekly intervals
beginning 2 (experiment 2a) or 4 d (experiment 2b) after insemination. The
earliest time point at which pregnant cows were accurately classified as pregnant
by the assay was on d 30 postinsemination. A transient decline in PAG levels into
the intermediate range was observed on d 46 to 72 postinsemination. This
coincides with the time of recheck in experiment 1. Results obtained with the
plasma samples were essentially the same. The accuracy of pregnancy
identification based on milk samples from nonpregnant and pregnant cows was 99%.
Levels of PAG in milk were useful in identifying 6 incidences of embryonic
mortality. No consistent relationship was noted between the timing of the decline
in PAG levels and the timing of luteal regression in this small number of cows.
PMID- 25129500
TI - Interaction between milk allowance and fat content of the starter feed on
performance of Holstein calves.
AB - Sixty-six Holstein male calves [42 +/- 6.0 kg of body weight (BW) and 12 +/- 3.1
d of age] were housed individually and allocated to 1 of 4 treatments following a
2 * 2 factorial complete randomized design to assess the potential interaction
between milk replacer (MR) allowance and fat content in the starter feed. Thus, 4
treatments were evaluated: a low-fat (4.1% fat; LF) starter feed offered along
with 4 L/d of MR (4 LF), a high-fat (11.2% fat; HF) starter feed plus 4 L/d of MR
(4 HF), a LF starter feed offered with 6 L/d of MR (6LF), and an HF starter feed
offered with 6 L/d of MR (6 HF). Calves were fed either 4 or 6 L/d of MR (25%
crude protein and 19.2% fat) in 2 offers (0800 and 1630 h) and had ad libitum
access to either an LF or an HF starter feed (21.4 and 22.3% crude protein).
Calves were weaned at wk 6 of study by halving the daily MR allowance for 1 wk.
Individual MR and starter feed intakes were recorded daily and BW was determined
weekly. A glucose tolerance test was performed on d 30 of study to evaluate the
effects of increased energy provision on glucose metabolism. Apparent feed
digestibility was measured for the last 5 d of study. Overall, fat content of
starter feed had no effect on solid feed intake. However, during wk 8 of study
(after weaning), calves in the LF treatment had greater starter feed intake than
HF calves. Calves on 6 L/d of MR had greater BW than calves fed 4 L/d from the
second week of study until weaning. After weaning, 6 LF calves had lesser BW than
6 HF calves. Calves on 6 L/d of MR had greater average daily gain than calves fed
4 L/d, and 6 HF calves tended to have the greatest average daily gain. Glucose
clearance rate tended to be lesser for HF than for LF calves. In conclusion,
offering 6 L/d of MR increased growth performance before weaning and, when
offering 6 L/d of MR, feeding a high-fat starter feed resulted in the greatest BW
after weaning.
PMID- 25129501
TI - Effect of curd washing on the properties of reduced-calcium and standard-calcium
Cheddar cheese.
AB - Washed (W) and nonwashed (NW) variants of standard (SCa) and reduced-calcium
(RCa) Cheddar cheeses were made in triplicate, ripened for a 270-d period, and
analyzed for composition and changes during maturation. Curd washing was applied
to cheeses to give a target level of lactose plus lactic acid in cheese moisture
of 3.9 g/100 g in the W cheese, compared with a value of 5.3 g/100 g of lactose
plus lactic acid in cheese moisture in the control NW cheeses. The 4 cheese types
were denoted standard calcium nonwashed (SCaNW), standard calcium washed (SCaW),
reduced-calcium nonwashed (RCaNW), and reduced-calcium washed (RCaW). The mean
calcium level was 760 mg/100 g in the SCaNW and SCaW and 660 mg/100 g in the
RCaNW and RCaW cheeses. Otherwise the gross composition of all cheeses was
similar, each with protein, fat, and moisture levels of ~26, 32, and 36 g/100 g,
respectively. Curd washing significantly reduced the mean level of lactic acid in
the SCaW cheese and residual lactose in both SCaW and RCaW cheeses. The mean pH
of the standard-calcium cheese over the 270-d ripening period increased
significantly with curd washing and ripening time, in contrast to the reduced
calcium cheese, which was not affected by the latter parameters. Otherwise curd
washing had little effect on changes in populations of starter bacteria or
nonstarter lactic acid bacteria, proteolysis, rheology, or color of the cheese
during ripening. Descriptive sensory analysis at 270 d indicated that the SCaW
cheese had a nuttier, sweeter, less fruity, and less rancid taste than the
corresponding SCaNW cheese. In contrast, curd washing was not as effective in
discriminating between the RCaW and RCaNW cheeses. The RCaW cheese had a more
buttery, caramel odor and flavor, and a more bitter, less sweet, and nutty taste
than the SCaW cheese, whereas the RCaNW had a more pungent and less fruity
flavor, a less fruity odor, a saltier, more-bitter, and less acidic taste, and a
more astringent mouthfeel than SCaNW. Washing of curd during manufacture provides
a means of reducing the contents of lactic acid and residual lactose, increasing
pH, and altering the sensory properties of Cheddar cheese, with the level of
these effects being significantly less pronounced as the calcium content was
reduced.
PMID- 25129502
TI - Investigation of bacterial and fungal diversity in tarag using high-throughput
sequencing.
AB - This is the first study on the bacterial and fungal community diversity in 17
tarag samples (naturally fermented dairy products) through a metagenomic approach
involving high-throughput pyrosequencing. Our results revealed the presence of a
total of 47 bacterial and 43 fungal genera in all tarag samples, in which
Lactobacillus and Galactomyces were the predominant genera of bacteria and fungi,
respectively. The number of some microbial genera, such as Lactococcus,
Acetobacter, Saccharomyces, Trichosporon, and Kluyveromyces, among others, was
found to vary between different samples. Altogether, our results showed that the
microbial flora in different samples may be stratified by geographic region.
PMID- 25129503
TI - NMO spectrum of disorders: a paradigm for astrocyte-targeting autoimmunity and
its implications for MS and other CNS inflammatory diseases.
AB - When studying a rare or orphan disease, we hope to shed light on more prevalent
syndromes. Neuromyelitis optica (NMO), also known as Devic's disease, is a rare
disease with a prevalence of about 4 in 100,000. Since 2005 when the anti
Aquaporin 4 (AQP4) NMO autoantibody was discovered by Lennon's group at the Mayo
clinic, an enormous amount of data have been acquired on the pathogenesis of the
disease. A review of the literature showed 47 relevant publications in 2004,
compared with 353 in 2013. The auto-antigen AQP4 is expressed on the astrocytic
foot processes suggesting a role for astrocytes in the pathogenesis of the
disease. However, the astrocytes might play a more active role than has
previously been suggested in the immune cascade of NMO pathology. Here we will
review epidemiological, clinical diagnostic and therapeutic aspects of NMO and
highlight the possible role of astrocytes as major direct and indirect players in
the pathogenesis of NMO and related CNS inflammatory diseases.
PMID- 25129504
TI - Thymic CCL2 influences induction of T-cell tolerance.
AB - Thymic epithelial cells (TEC) and dendritic cells (DC) play a role in T cell
development by controlling the selection of the T cell receptor repertoire. DC
have been described to take up antigens in the periphery and migrate into the
thymus where they mediate tolerance via deletion of autoreactive T cells, or by
induction of natural regulatory T cells. Migration of DC to thymus is driven by
chemokine receptors. CCL2, a major ligand for the chemokine receptor CCR2, is an
inflammation-associated chemokine that induces the recruitment of immune cells in
tissues. CCL2 and CCR2 are implicated in promoting experimental autoimmune
encephalomyelitis (EAE), a mouse model for multiple sclerosis. We here show that
CCL2 is constitutively expressed by endothelial cells and TEC in the thymus.
Transgenic mice overexpressing CCL2 in the thymus showed an increased number of
thymic plasmacytoid DC and pronounced impairment of T cell development.
Consequently, CCL2 transgenic mice were resistant to EAE. These findings
demonstrate that expression of CCL2 in thymus regulates DC homeostasis and
controls development of autoreactive T cells, thus preventing development of
autoimmune diseases.
PMID- 25129506
TI - Invasive lobular breast cancer and its variants: how special are they for
systemic therapy decisions?
AB - The WHO classification of breast tumors distinguishes, besides invasive breast
cancer 'of no special type' (former invasive ductal carcinoma, representing 60
70% of all breast cancers), 30 special types, of which invasive lobular carcinoma
(ILC) is the most common (5-15%). We review the literature on (i) the specificity
and heterogeneity of ILC biology as documented by various analytical techniques,
including the results of molecular testing for risk of recurrence; (ii) the
impact of lobular histology on prediction of prognosis and effect of systemic
therapies in patients. Though it is generally admitted that ILC has a better
prognosis than IDC, is endocrine responsive, and responds poorly to chemotherapy,
currently available data do not unanimously support these assumptions. This
review demonstrates some lack of specific data and a need for improving clinical
research design to allow oncologists to make informed systemic therapy decisions
in patients with ILC. Importantly, future studies should compare various
endpoints in ILC breast cancer patients among the group of hormonosensitive
breast cancer.
PMID- 25129505
TI - Evaluation of textile substrates for dispensing synthetic attractants for malaria
mosquitoes.
AB - BACKGROUND: The full-scale impact of odour-baited technology on the surveillance,
sampling and control of vectors of infectious diseases is partly limited by the
lack of methods for the efficient and sustainable dispensing of attractants. In
this study we investigated whether locally-available and commonly used textiles
are efficient substrates for the release of synthetic odorant blends attracting
malaria mosquitoes. METHODS: The relative efficacy of (a) polyester, (b) cotton,
(c) cellulose + polyacrylate, and (d) nylon textiles as substrates for dispensing
a synthetic odour blend (Ifakara blend 1(IB1)) that attracts malaria mosquitoes
was evaluated in western Kenya. The study was conducted through completely
randomized Latin square experimental designs under semi-field and field
conditions. RESULTS: Traps charged with IB1-impregnated polyester, cotton and
cellulose + polyacrylate materials caught significantly more female Anopheles
gambiae sensu stricto (semi-field conditions) and An. gambiae sensu lato (field
conditions) mosquitoes than IB1-treated nylon (P = 0.001). The IB1-impregnated
cellulose + polyacrylate material was the most attractive to female An. funestus
mosquitoes compared to all other dispensing textile substrates (P < 0.001). The
responses of female An. funestus mosquitoes to IB1-treated cotton and polyester
were equal (P = 0.45). Significantly more female Culex mosquitoes were attracted
to IB1-treated cotton than to the other treatments (P < 0.001). Whereas IB1
impregnated cotton and cellulose + polyacrylate material attracted equal numbers
of female Mansonia mosquitoes (P = 0.44), the catches due to these two substrates
were significantly higher than those associated with the other substrates (P <
0.001). CONCLUSION: The number and species of mosquitoes attracted to a synthetic
odour blend is influenced by the type of odour-dispensing material used. Thus,
surveillance and intervention programmes for malaria and other mosquito vectors
using attractive odour baits should select an odour-release material that
optimizes the odour blend.
PMID- 25129507
TI - One-pot synthesis of GO/AgNPs/luminol composites with electrochemiluminescence
activity for sensitive detection of DNA methyltransferase activity.
AB - DNA methyltransferases catalyze the transfer of a methyl group from S
adenosylmethionine to the target adenine or cytosine, eventually inducing the DNA
methylation in both prokaryotes and eukaryotes. Herein, we developed a novel
electrochemiluminescence biosensor to quantify DNA adenine methylation (Dam)
methyltransferase (MTase) employing signal amplification of GO/AgNPs/luminol
composites to enhance the assay sensitivity. The method was developed by
designing a capture probe DNA, which was immobilized on gold electrode surface,
to hybridize with azide complementary DNA to form the azide-terminated dsDNA.
Then, alkynyl functionalized GO/AgNPs/luminol composites as the signal probe were
immobilized to azide-terminated dsDNA modified electrode via click chemistry,
resulting in a high electrochemiluminescence (ECL) signal. Once the DNA hybrid
was methylated (under catalysis of Dam MTase) and further cleaved by Dpn I
endonuclease (a site-specific endonuclease recognizing the duplex symmetrical
sequence of 5'-G-Am-T-C-3'), GO/AgNPs/luminol composites release from the
electrode surface to the solution, leading to significant reduction of the ECL
signal. The change of the ECL intensity is related to the methylation status and
MTase activity, which forms the basis of MTase activity assay and site-specific
methylation determination. This novel strategy can be further used as a universal
method for other transferase determination by designing various transferase
specific DNA sequences. In addition, this method can be used for the screening of
antimicrobial drugs and has a great potential to be further applied in early
clinical diagnosis.
PMID- 25129508
TI - Ultrasensitive electrochemical immunoassay for CEA through host-guest interaction
of beta-cyclodextrin functionalized graphene and Cu@Ag core-shell nanoparticles
with adamantine-modified antibody.
AB - A novel non-enzymatic immunoassay was designed for ultrasensitive electrochemical
detection of carcino-embryonic antigen (CEA) using beta-cyclodextrin
functionalized Cu@Ag (Cu@Ag-CD) core-shell nanoparticles as labels and beta
cyclodextrin functionalized graphene nanosheet (CD-GN) as sensor platform. CD-GN
has excellent conductivity which promoted the electric transmission between base
solution and electrode surface and enhanced sensitivity of immunosensor. In
addition, owing to supramolecular recognition of CD-GN for the guest molecule,
quite a few synthesized adamantine-modified primary antibodies (ADA-Ab1) were
immobilized on the CD-GN by supramolecular host-guest interaction between CD and
ADA. Cu@Ag-CD as a signal tag could be captured by ADA-modified secondary
antibody (ADA-Ab2) through a host-guest interaction, leading to a large loading
of Cu@Ag nanoparticles with high electrical conductivity and catalytic activity.
The fabricated immunosensor exhibits excellent analytical performance for the
measurement of CEA with wide range linear (0.0001-20 ng/mL), low detection limit
(20 fg/mL), good sensitivity, reproducibility and stability, which provide an
enormous application prospect in clinical diagnostics.
PMID- 25129510
TI - Electrogenerated chemiluminescence behavior of peptide nanovesicle and its
application in sensing dopamine.
AB - The electrogenerated chemiluminescence (ECL) behavior of the bioinspired peptide
nanovesicles (PNVs) was reported for the first time. The PNVs modified glassy
carbon electrodes have shown a stable and efficient cathodic ECL signal with
K2S2O8 as coreactant in aqueous solution. The possible ECL reaction mechanism was
proposed. Dopamine (DA) was chosen as a model analyte to study the potential of
the PNVs in the ECL analytical application. It was found that the ECL intensity
of the PNVs was effectively increased by trace amounts of DA. The limit of
detection was estimated to be 3.15 pM (S/N=3). These results suggest that the
PNVs could be a new class of promising materials for the ECL design and bioassays
in the future due to their fascinating features, such as excellent
biocompatibility, tunable composition as well as capability of molecular
recognition.
PMID- 25129509
TI - Engineering plasmonic nanorod arrays for colon cancer marker detection.
AB - Engineering plasmonic nanomaterials or nanostructures towards ultrasensitive
biosensing for disease markers or pathogens is of high importance. Here we
demonstrate a systematic approach to tailor effective plasmonic nanorod arrays by
combining both comprehensive numerical discrete dipole approximations (DDA)
simulation and transmission spectroscopy experiments. The results indicate that
200*50 nm nanorod arrays with 300*500 nm period provide the highest figure of
merit (FOM) of 2.4 and a sensitivity of 310 nm/RIU. Furthermore, we demonstrate
the use of nanorod arrays for the detection of single nucleotide polymorphism in
codon 12 of the K-ras gene that are frequently occurring in early stages of colon
cancer, with a sensitivity down to 10 nM in the presence of 100-fold higher
concentration of the homozygous genotypes. Our work shows significant potential
of nanorod arrays towards point-of-care applications in diagnosis and clinical
studies.
PMID- 25129511
TI - One-pot synthesis of 3-dimensional reduced graphene oxide-based hydrogel as
support for microbe immobilization and BOD biosensor preparation.
AB - We report a hydrothermal method to prepare reduced graphene oxide (rGO)-based
hydrogel (Gel(rGONR)), using neutral red (NR) to mediate the assembly of rGO
sheets and tune the pore size of Gel(rGONR). A series of techniques including
scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), X-ray
diffraction (XRD), Raman spectroscopy and BET were employed to characterize the
physico-chemical properties of Gel(rGONR). A large pore size of up to 20 um and
interconnected porous structure of Gel(rGONR) were obtained. Gel(rGONR) was used
as a support for immobilizing microbe (denoted as Gel(rGONR-M)), which showed
~3.3 times more load mass of microbe than commonly used supports (i.e., activated
carbon and carbon fiber felt) and 2.5 times higher biodegradation efficiency (BE)
than carbon fiber felt. Further use of Gel(rGONR-M) as a biocatalyst for
establishing a BOD biosensor exhibits a linear range of 2-64 mg O L(-1) and a
detection limit 0.4 mg O L(-1) for glucose-glutamic acid (GGA). Moreover, our
proposed BOD detection strategy shows a long-term viability over one year and
stability up to 2 months with a relative standard deviation of 2.1%. Our results
demonstrated the great potential of employing Gel(rGONR) as a microbe
immobilization support for biosensor development.
PMID- 25129512
TI - A novel modified electrode as GC/PPy-AuNPs-rGO/L-Cys/Ag@MUA nanostructure
configuration for determination of CCP and CRP antibodies in human blood serum
samples.
AB - In this work, silver nanoparticles were synthesized and stabilized with 11
mercaptoundecanoateanions to produce a new Ag@MUA core shell structure, and its
utilizing for fabrication of a new sensing film. Gold nanoparticles (AuNPs) were
electrochemically produced and simultaneously immobilized into the
electropolymerized polypyrrole (PPy) film with the reduced graphene oxide (rGO).
The Ag@MUA was then grafted to the surface of GC/PPy-AuNPs-rGO film using L
cysteine (L-Cys) linker agent and trifluoromethanesulfonic anhydride (TF2O), at
ambient temperature and under the electrode stirring. The characterization of the
sensor was studied by scanning electron microscopy, electrochemical impedance
spectroscopy, cyclic and square wave voltammetry techniques. The utility of the
modified electrode for clinical diagnosis has been successfully demonstrated by
the analysis of human blood serums with a certified CRP and CCP content. Thus,
the proposed sensor shows simple preparation, accuracy and precision in the
analysis of cytochrome c protein (CCP) and C-reactive protein (CRP (with less
side interferences.
PMID- 25129513
TI - Green synthesis and molecular recognition ability of patuletin coated gold
nanoparticles.
AB - Patuletin isolated from Tagetespatula was used as a capping and reducing agent to
synthesize in one pot gold nanoparticles capped with patuletin. Conjugation of
gold with patuletin was confirmed by FT-IR and UV-visible spectroscopy and amount
of patuletin conjugated to gold nanoparticles was found to be 63.2% by weight.
Particle sizes were measured by atomic force microscopy (AFM) and were found to
have a mean diameter of about 45 nm. Patuletin-coated gold nanoparticles were
found to be highly fluorescent. To examine their potential as chemical sensors,
they were contacted with fourteen different drugs. Of these drugs, only one,
piroxicam, was found to quench luminescence. Quenching obeyed Beer's law in a
concentration range of 20-260 uM. Important for molecular recognition
applications, fluorescence quenching by piroxicam was not affected by pH
variation, elevated temperatures, addition of other drugs and addition of blood
plasma to the colloidal suspensions.
PMID- 25129514
TI - Epithelial-derived nuclear IL-33 aggravates inflammation in the pathogenesis of
reflux esophagitis.
AB - BACKGROUND: IL-33 is a new tissue-derived cytokine constitutively expressed in
epithelial cells and plays a role in sensing damage caused by inflammatory
diseases. The function of IL-33 in the esophageal mucosa has not been previously
described. Accordingly, we examined the expression of IL-33 and its role in the
pathogenesis of reflux esophagitis (RE). METHODS: IL-33 in the esophageal mucosa
of RE patients and in an in vitro stratified normal esophageal squamous
epithelial model was examined at the messenger RNA and protein levels. The
correlation of the level of IL-33 and IL-8 or IL-6 was examined. Cell layers were
stimulated with bile acids and cytokines. IL-33 was knocked down by small
interfering RNA (siRNA). Pharmacological inhibitors and signal transducer and
activator of transcription 1 (STAT1) siRNA were used. RESULTS: IL-33 was
significantly upregulated in RE patients, and was located in the nuclei of basal
and suprabasal layers. Upregulated IL-33 messenger RNA expression was correlated
with IL-8 and IL-6 expression. In vitro, IL-33 was upregulated in the nuclei of
basal and suprabasal layers by interferon-gamma (IFNgamma), and the upregulation
was aggravated by the combination of deoxycholic acid (DCA) and IFNgamma. IL-33
knockdown dampened IFNgamma- and DCA-induced IL-8 and IL-6 production. IFNgamma
induced IL-33 was inhibited by a Janus kinase inhibitor, a p38 mitogen-activated
protein kinase inhibitor, and STAT1 siRNA. CONCLUSIONS: Nuclear IL-33 is
upregulated in erosive mucosa of RE patients and is correlated with IL-8 and IL-6
levels. The normal esophageal epithelial model enables us to show for the first
time that epithelial-cell-derived nuclear but not exogenous IL-33 is located
upstream of the production of inflammatory cytokines and can aggravate the
inflammation.
PMID- 25129515
TI - A cluster-randomized controlled trial to assess the effectiveness of using 15%
DEET topical repellent with long-lasting insecticidal nets (LLINs) compared to a
placebo lotion on malaria transmission.
AB - BACKGROUND: Long-lasting insecticidal nets (LLINs) have limited effect on malaria
transmitted outside of sleeping hours. Topical repellents have demonstrated
reduction in the incidence of malaria transmitted in the early evening. This
study assessed whether 15% DEET topical repellent used in combination with LLINs
can prevent greater malaria transmission than placebo and LLINs, in rural
Tanzania. METHODS: A cluster-randomized, placebo-controlled trial was conducted
between July 2009 and August 2010 in a rural Tanzanian village. Sample size
calculation determined that 10 clusters of 47 households with five
people/household were needed to observe a 24% treatment effect at the two-tailed
5% significance level, with 90% power, assuming a baseline malaria incidence of
one case/person/year. Ten clusters each were randomly assigned to repellent and
control groups by lottery. A total of 4,426 individuals older than six months
were enrolled. All households in the village were provided with an LLIN per
sleeping space. Repellent and placebo lotion was replaced monthly. The main
outcome was rapid diagnostic test (RDT)-confirmed malaria measured by passive
case detection (PCD). Incidence rate ratios were estimated from a Poisson model,
with adjustment for potential confounders, determined a priori. According-to
protocol approach was used for all primary analyses. RESULTS: The placebo group
comprised 1972.3 person-years with 68.29 (95% C.I 37.05-99.53) malaria
cases/1,000 person-years. The repellent group comprised 1,952.8 person-years with
60.45 (95% C.I 48.30-72.60) cases/1,000 person-years, demonstrating a non
significant 11.44% reduction in malaria incidence rate in this group, (Wilcoxon
rank sum z=0.529, p=0.596). Principal components analysis (PCA) of the socio
economic status (SES) of the two groups demonstrated that the control group had a
higher SES (Pearson's chi square=13.38, p=0.004). CONCLUSIONS: Lack of an
intervention effect was likely a result of lack of statistical power, poor
capture of malaria events or bias caused by imbalance in the SES of the two
groups. Low malaria transmission during the study period could have masked the
intervention effect and a larger study size was needed to increase discriminatory
power. Alternatively, topical repellents may have no impact on malaria
transmission in this scenario. Design and implementation of repellent
intervention studies is discussed. TRIAL REGISTRATION: The trial was registered
ISRCTN92202008--http://www.controlled-trials.com/ISRCTN92202008.
PMID- 25129516
TI - Value of CMR for the differential diagnosis of cardiac masses.
AB - OBJECTIVES: The goal of this study was to evaluate the diagnostic value of CMR
features for the differential diagnosis of cardiac masses. BACKGROUND:
Differentiation of cardiac tumors and thrombi and differentiation of benign from
malignant cardiac neoplasms is often challenging but important in clinical
practice. Studies assessing the value of cardiac magnetic resonance (CMR) in this
regard are scarce. METHODS: We reviewed the CMR scans of patients with a definite
cardiac thrombus or tumor. Mass characteristics on cine, T1-weighted turbo spin
echo (T1w-TSE) and T2-weighted turbo spin echo (T2w-TSE), contrast first-pass
perfusion (FPP), post-contrast inversion time (TI) scout, and late gadolinium
enhancement (LGE) sequences were analyzed. RESULTS: There were 84 thrombi, 17
benign tumors, and 25 malignant tumors in 116 patients. Morphologically, thrombi
were smaller (median area 1.6 vs. 8.5 cm(2); p < 0.0001), more homogeneous (99%
vs. 46%; p < 0.0001), and less mobile (13% vs. 33%; p = 0.007) than tumors.
Hyperintensity compared with normal myocardium on T2w-TSE, FPP, and LGE were more
common in tumors than in thrombi (85% vs. 42%, 70% vs. 4%, and 71% vs. 5%,
respectively; all p < 0.0001). A pattern of hyperintensity/isointensity (compared
with normal myocardium) with short TI and hypointensity with long TI was very
frequent in thrombi (94%), rare in tumors (2%), and had the highest accuracy
(95%) for the differentiation of both entities. Regarding the characterization of
neoplastic masses, malignant tumors were larger (median area 11.9 vs. 6.3 cm(2);
p = 0.006) and more frequently exhibited FPP (84% vs. 47%; p = 0.03) and LGE (92%
vs. 41%; p = 0.001). The ability of CMR features to distinguish benign from
malignant neoplasms was moderate, with LGE showing the highest accuracy (79%).
CONCLUSIONS: CMR features demonstrated excellent accuracy for the differentiation
of cardiac thrombi from tumors and can be helpful for the distinction of benign
versus malignant neoplasms.
PMID- 25129517
TI - Compressed sensing single-breath-hold CMR for fast quantification of LV function,
volumes, and mass.
AB - OBJECTIVES: The purpose of this study was to compare a novel compressed sensing
(CS)-based single-breath-hold multislice magnetic resonance cine technique with
the standard multi-breath-hold technique for the assessment of left ventricular
(LV) volumes and function. BACKGROUND: Cardiac magnetic resonance is generally
accepted as the gold standard for LV volume and function assessment. LV function
is 1 of the most important cardiac parameters for diagnosis and the monitoring of
treatment effects. Recently, CS techniques have emerged as a means to accelerate
data acquisition. METHODS: The prototype CS cine sequence acquires 3 long-axis
and 4 short-axis cine loops in 1 single breath-hold (temporal/spatial resolution:
30 ms/1.5 * 1.5 mm(2); acceleration factor 11.0) to measure left ventricular
ejection fraction (LVEF(CS)) as well as LV volumes and LV mass using LV model
based 4D software. For comparison, a conventional stack of multi-breath-hold cine
images was acquired (temporal/spatial resolution 40 ms/1.2 * 1.6 mm(2)). As a
reference for the left ventricular stroke volume (LVSV), aortic flow was measured
by phase-contrast acquisition. RESULTS: In 94% of the 33 participants (12
volunteers: mean age 33 +/- 7 years; 21 patients: mean age 63 +/- 13 years with
different LV pathologies), the image quality of the CS acquisitions was
excellent. LVEF(CS) and LVEF(standard) were similar (48.5 +/- 15.9% vs. 49.8 +/-
15.8%; p = 0.11; r = 0.96; slope 0.97; p < 0.00001). Agreement of LVSV(CS) with
aortic flow was superior to that of LVSV(standard) (overestimation vs. aortic
flow: 5.6 +/- 6.5 ml vs. 16.2 +/- 11.7 ml, respectively; p = 0.012) with less
variability (r = 0.91; p < 0.00001 for the CS technique vs. r = 0.71; p < 0.01
for the standard technique). The intraobserver and interobserver agreement for
all CS parameters was good (slopes 0.93 to 1.06; r = 0.90 to 0.99). CONCLUSIONS:
The results demonstrated the feasibility of applying the CS strategy to evaluate
LV function and volumes with high accuracy in patients. The single-breath-hold CS
strategy has the potential to replace the multi-breath-hold standard cardiac
magnetic resonance technique.
PMID- 25129519
TI - Practical guidance in echocardiographic assessment of global longitudinal strain.
PMID- 25129518
TI - The natural history of left ventricular geometry in the community: clinical
correlates and prognostic significance of change in LV geometric pattern.
AB - OBJECTIVES: This study sought to evaluate pattern and clinical correlates of
change in left ventricular (LV) geometry over a 4-year period in the community;
it also assessed whether the pattern of change in LV geometry over 4 years
predicts incident cardiovascular disease (CVD), including myocardial infarction,
heart failure, and cardiovascular death, during an additional subsequent follow
up period. BACKGROUND: It is unclear how LV geometric patterns change over time
and whether changes in LV geometry have prognostic significance. METHODS: This
study evaluated 4,492 observations (2,604 unique Framingham Heart Study
participants attending consecutive examinations) to categorize LV geometry at
baseline and after 4 years. Four groups were defined on the basis of the sex
specific distributions of left ventricular mass (LVM) and relative wall thickness
(RWT) (normal: LVM and RWT <80th percentile; concentric remodeling: LVM <80th
percentile but RWT >=80th percentile; eccentric hypertrophy: LVM >=80th
percentile but RWT <80th percentile; and concentric hypertrophy: LVM and RWT
>=80th percentile). RESULTS: At baseline, 2,874 of 4,492 observations (64%) had
normal LVM and RWT. Participants with normal geometry or concentric remodeling
progressed infrequently (4% to 8%) to eccentric or concentric hypertrophy. Change
from eccentric to concentric hypertrophy was uncommon (8%). Among participants
with concentric hypertrophy, 19% developed eccentric hypertrophy within the 4
year period. Among participants with abnormal LV geometry at baseline, a
significant proportion (29% to 53%) reverted to normal geometry within 4 years.
Higher blood pressure, greater body mass index (BMI), advancing age, and male sex
were key correlates of developing an abnormal geometry. Development of an
abnormal LV geometric pattern over 4 years was associated with increased CVD risk
(140 events) during a subsequent median follow-up of 12 years (adjusted-hazards
ratio: 1.59; 95% confidence interval: 1.04 to 2.43). CONCLUSIONS: The
longitudinal observations in the community suggest that dynamic changes in LV
geometric pattern over time are common. Higher blood pressure and greater BMI are
modifiable factors associated with the development of abnormal LV geometry, and
such progression portends an adverse prognosis.
PMID- 25129520
TI - Educational intervention to reduce outpatient inappropriate echocardiograms: a
randomized control trial.
AB - OBJECTIVES: This study sought to prospectively study the impact of an appropriate
use criteria (AUC)-based educational intervention on outpatient transthoracic
echocardiography (TTE) ordering by physicians-in-training. BACKGROUND: AUC were
developed in response to concerns about inappropriate utilization. It is unknown
whether an educational intervention can reduce inappropriate outpatient TTE.
METHODS: We conducted a randomized control trial in which physicians-in-training
were randomized to an AUC-based educational intervention or a control group at an
academic medical center in Boston, Massachusetts. The primary endpoints were the
rates of inappropriate and appropriate TTE. RESULTS: For the cardiology
physicians-in-training, the proportion of inappropriate TTE was significantly
lower in the intervention than in the control group (13% vs. 34%, p < 0.001). As
a corollary, the proportion of appropriate TTE ordered by the intervention group
was significantly higher than that of the control group (81% vs. 58%, p < 0.001).
The odds of ordering an appropriate TTE in the cardiology intervention group was
2.7 (95% confidence interval [CI]: 1.5 to 5.1, p = 0.002) relative to the control
group. The internal medicine physicians-in-training ordered a small number of TTE
overall, and there was a trend toward significant odds of ordering an appropriate
TTE in the intervention group relative to the control group (odds ratio [OR]:
8.1, 95% CI: 0.95 to 69.0, p = 0.055). Six clinical scenarios accounted for 75%
of all inappropriate TTE, with the 3 most common inappropriate indications being
routine surveillance (<1 year) of known cardiomyopathy without a change in
clinical status, routine surveillance of known small pericardial effusion, and
routine surveillance of ventricular function with known coronary artery disease
and no change in clinical status. CONCLUSIONS: In cardiology fellows with a high
rate of ordering inappropriate TTE, an AUC-based educational and feedback
intervention reduced the proportion of inappropriate outpatient TTE and increased
the proportion of appropriate outpatient TTE. (Educational Intervention to Reduce
Outpatient Inappropriate Transthoracic Echocardiograms; NCT01944202).
PMID- 25129522
TI - Now you see me, now you don't: iridescence increases the efficacy of lizard
chromatic signals.
AB - The selective forces imposed by primary receivers and unintended eavesdroppers of
animal signals often act in opposite directions, constraining the development of
conspicuous coloration. Because iridescent colours change their chromatic
properties with viewer angle, iridescence offers a potential mechanism to relax
this trade-off when the relevant observers involved in the evolution of signal
design adopt different viewer geometries. We used reflectance spectrophotometry
and visual modelling to test if the striking blue head coloration of males of the
lizard Lacerta schreibeiri (1) is iridescent and (2) is more conspicuous when
viewed from the perspective of conspecifics than from that of the main predators
of adult L. schreibeiri (raptors). We demonstrate that the blue heads of L.
schreiberi show angle-dependent changes in their chromatic properties. This
variation allows the blue heads to be relatively conspicuous to conspecific
viewers located in the same horizontal plane as the sender, while simultaneously
being relatively cryptic to birds that see it from above. This study is the first
to suggest the use of angle-dependent chromatic signals in lizards, and provides
the first evidence of the adaptive function of iridescent coloration based on its
detectability to different observers.
PMID- 25129521
TI - Accumulation of fatty acids in Chlorella vulgaris under heterotrophic conditions
in relation to activity of acetyl-CoAcarboxylase, temperature, and co
immobilization with Azospirillum brasilense [corrected].
AB - The relation between fatty acid accumulation, activity of acetyl-CoA carboxylase
(ACC), and consequently lipid accumulation was studied in the microalgae
Chlorella vulgaris co-immobilized with the plant growth-promoting bacterium
Azospirillum brasilense under dark heterotrophic conditions with Na acetate as a
carbon source. In C. vulgaris immobilized alone, cultivation experiments for 6
days showed that ACC activity is directly related to fatty acid accumulation,
especially in the last 3 days. In co-immobilization experiments, A. brasilense
exerted a significant positive effect over ACC activity, increased the quantity
in all nine main fatty acids, increased total lipid accumulation in C. vulgaris,
and mitigated negative effects of nonoptimal temperature for growth. No
correlation between ACC activity and lipid accumulation in the cells was
established for three different temperatures. This study demonstrated that the
interaction between A. brasilense and C. vulgaris has a significant effect on
fatty acid and lipid accumulation in the microalgae.
PMID- 25129523
TI - Staged seton fistulotomy after restorative proctocolectomy with ileal pouch-anal
anastomosis accompanied by a decline in anal pressure during manometry.
PMID- 25129524
TI - Cecal recurrence after one-stage resection of obstructive rectal cancer with
intraoperative colonic lavage through the appendix: a curious coincidence.
PMID- 25129525
TI - Massive colonic metastasis from breast cancer 23 years after mastectomy.
PMID- 25129526
TI - [Out of hospital emergencies towards a safety culture].
AB - OBJECTIVES: The aim of this study is to measure the degree of safety culture (CS)
among healthcare professional workers of an out-of-hospital Emergency Medical
Service. Most patient safety studies have been conducted in relation to the
hospital rather than pre-hospital Emergency Medical Services. The objective is to
analyze the dimensions with lower scores in order to plan futures strategies.
MATERIAL AND METHODS: A descriptive study using the AHRQ (Agency for Healthcare
Research and Quality) questionnaire. The questionnaire was delivered to all
healthcare professionals workers of 061 Advanced Life Support Units of Aragon,
during the month of August 2013. RESULTS: The response rate was 55%. Main
strengths detected: an adequate number of staff (96%), good working conditions
(89%), tasks supported from immediate superior (77%), teamwork climate (74%), and
non-punitive environment to report adverse events (68%). Areas for improvement:
insufficient training in patient safety (53%) and lack of feedback of incidents
reported (50%). CONCLUSIONS: The opportunities for improvement identified focus
on the training of professionals in order to ensure safer care, while extending
the safety culture. Also, the implementation of a system of notification and
registration of adverse events in the service is deemed necessary.
PMID- 25129527
TI - [Intervention in elderly patients with multiple morbidities and multiple
medications: results of the prescription and the quality of life].
AB - OBJECTIVE: To evaluate the effect of an intervention using STOPP/START criteria
and the Garfinkel algorithm on prescription and the health-related quality of
life (HRQoL) in elderly patients with multimorbidity and prescribed multiple
medications. MATERIAL AND METHOD: A before-after intervention study on 381
patients over 67 years old and prescribed multiple medications by 71 Primary Care
doctors. INTERVENTION: The doctors were trained in the STOPP / START criteria and
Garfinkel algorithm. Each doctor then reviewed all the drugs of their selected
patients and then made appointments with them for an initial medical consultation
and clinical assessment. Treatment was modified according to the criteria and the
HRQoL measured using the SF-12 questionnaire. Two months later, in a second
medical consultation, a new clinical assessment was made and the HRQoL was
measured. The dimensions of the HRQoL between the first and the second
consultation were compared using the paired Student-t test. RESULTS: The
intervention involved the removal of a mean of 1.5 drugs per patient. The dose
was modified in 4% of drugs, and 8.9% of patients were prescribed a new drug. Non
Steroidal Anti-inflammatory drugs (NSAID), psychoactive drugs and proton pump
inhibitors were the most modified. Social Function and Physical Component Summary
of the HRQOL improved significantly (P<.05) after intervention. CONCLUSION: The
intervention using the Garfinkel algorithm and STOPP -START criteria improved
HRQoL and reduced the number of prescribed drugs.
PMID- 25129528
TI - Beyond description: comment on "approaching human language with complex networks"
by Cong and Liu.
PMID- 25129529
TI - Fine structure of the midgut of Sinopanorpa tincta (Navas) (Mecoptera:
Panorpidae).
AB - Fine structure of the midgut and degeneration of the midgut epithelium of the
scorpionfly Sinopanorpa tincta (Navas) adults were investigated using light
microscopy and scanning and transmission electron microscopy. The results show
that the tubular midgut lacks gastric caeca and is composed of an outer
longitudinal and an inner circular muscle layer, a basal lamina, an epithelium
and a lumen from the outside to inside. A peritrophic membrane was not found in
the lumen. A mass of nodules was observed on the surface of the basal lamina.
Three types of cells were recognized in the epithelium: digestive, secretory, and
regenerative cells. The digestive cells contain irregular-shaped infoldings in
the basal membrane and two types of microvilli in the apical membrane. The
secretory cells are characterized by irregular shape and large quantities of
secretory granules in the basal cytoplasm. The regenerative cells are triangular
in shape and distributed only in the nodules. The epithelial cells are
degenerated through programmed cell-death mechanisms (apoptosis and necrosis).
The type, function, and degeneration of the epithelial cells of the midgut are
briefly discussed.
PMID- 25129530
TI - Effect of sporulation medium on wet-heat resistance and structure of
Alicyclobacillus acidoterrestris DSM 3922-type strain spores and modeling of the
inactivation kinetics in apple juice.
AB - Alicyclobacillus acidoterrestris is a spoilage bacterium in fruit juices leading
to high economic losses. The present study evaluated the effect of sporulation
medium on the thermal inactivation kinetics of A. acidoterrestris DSM 3922 spores
in apple juice (pH3.82+/-0.01; 11.3+/-0.1 degrees Brix). Bacillus acidocaldarius
agar (BAA), Bacillus acidoterrestris agar (BATA), malt extract agar (MEA), potato
dextrose agar (PDA) and B. acidoterrestris broth (BATB) were used for
sporulation. Inactivation kinetic parameters at 85, 87.5 and 90 degrees C were
obtained using the log-linear model. The decimal reduction times at 85 degrees C
(D85 degrees C) were 41.7, 57.6, 76.8, 76.8 and 67.2min; D87.5 degrees C-values
were 22.4, 26.7, 32.9, 31.5, and 32.9min; and D90 degrees C-values were 11.6,
9.9, 14.7, 11.9 and 14.1min for spores produced on PDA, MEA, BATA, BAA and BATB,
respectively. The estimated z-values were 9.05, 6.60, 6.96, 6.15, and 7.46,
respectively. The present study suggests that the sporulation medium affects the
wet-heat resistance of A. acidoterrestris DSM 3922 spores. Also, the dipicolinic
acid content (DPA) was found highest in heat resistant spores formed on mineral
containing media. After wet-heat treatment, loss of internal volume due to the
release of DPA from spore core was observed by scanning electron microscopy.
Since, there is no standardized media for the sporulation of A. acidoterrestris,
the results obtained from this study might be useful to determine and compare the
thermal resistance characteristics of A. acidoterrestris spores in fruit juices.
PMID- 25129531
TI - A web-based self-management intervention for Bipolar Disorder 'living with
bipolar': a feasibility randomised controlled trial.
AB - BACKGROUND: Bipolar Disorder (BD) is a severe mental health problem.
Psychological interventions are recommended by the National Institute for Health
and Care Excellence (NICE) but patients experience severe inequalities in access.
This study assessed the feasibility and potential effectiveness of a recovery
informed web-based self-management intervention for people with BD. METHODS: An
online randomised controlled trial (n=122) compared treatment as usual (TAU) plus
the 'Living with Bipolar' (LWB) intervention with a waiting list control (WLC)
group. RESULTS: The study recruited to target and the retention rates were high.
Participants engaged with the approach. Compared with the WLC, those receiving
LWB showed the most robust improvement in psychological and physical domains of
quality of life, wellbeing and recovery at the end of the intervention.
LIMITATIONS: The trial was not definitive and requires further investigation.
CONCLUSIONS: There is preliminary evidence that a web-based treatment approach in
BD is feasible and potentially effective. Such interventions could form part of
the Improving Access to Psychological Therapy (IAPT) initiative in severe mental
health.
PMID- 25129532
TI - Dysfunctional traits in obese women and underweight men.
AB - BACKGROUND: The prevalence of obesity is rapidly increasing worldwide, together
with its comorbidities. Our aim was to assess the emotional traits and affective
temperaments, according to various Body Mass Index (BMI) groups, in a large
sample. METHODS: Data was collected by a web-survey on psychological and
psychiatric measures (BRAINSTEP). The BMI was evaluated by self-reporting and
temperament was evaluated by the Affective and Emotional Composite Temperament
Scale (AFECTS). The final sample consisted of 10,786 individuals (mean age 27.9
+/- 7.8 years, 70% females). RESULTS: About 40% of the sample had a BMI score
higher than normal. The overall BMI score was particularly associated with a
higher Desire and a lower Control and Volition (p<0.001 for all), especially in
women. Obese females also had significantly lower Coping, Stability, and Caution.
In males only, underweight individuals were more fearful and sensitive, and they
had a lower Coping and Volition character than normal weight subjects, suggesting
a more fragile and immature profile. Linear regression with several adjustments
confirmed these associations. Regarding affective temperaments, a Depressive type
was more prevalent among underweight subjects, an Obsessive type was associated
with a normal BMI, and a Hyperthymic type was apparent in overweight individuals
of both genders. Underweight males and females were more prone to having an
internalized temperament. LIMITATIONS: Only self-reporting measures were used in
a cross-sectional design. CONCLUSIONS: Obese women and underweight men have a
more dysfunctional trait profile. Addressing these traits may be important for
prevention strategies and, possibly, for weight reduction in women.
PMID- 25129534
TI - PTSD prevalence and symptom structure of DSM-5 criteria in adolescents and young
adults surviving the 2011 shooting in Norway.
AB - BACKGROUND: Diagnostic criteria for Posttraumatic Stress Disorder (PTSD) have
been revised for DSM-5. Two key changes include alteration of the clustering of
PTSD symptoms and new PTSD symptom criteria related to negative alterations in
cognition and mood. In this study, we empirically investigated these changes.
METHODS: We interviewed 325 adolescents and young adults who survived the 2011
youth camp shooting at Utoya Island, Norway. The UCLA PTSD Reaction Index for DSM
IV was used to assess symptoms of PTSD. In addition, 11 questions were added to
assess the four new symptom criteria within the new DSM-5 symptom categories.
RESULTS: PTSD prevalence did not differ significantly whether DSM-IV (11.1%) or
DSM-5 (11.7%) criteria were used and the Cohen's Kappa for consistency between
the diagnoses was 0.061. Confirmatory factor analyses showed that the four-factor
structure of the DSM-5 fit the data adequately according to the conceptual model
outlined. LIMITATIONS: The homogeneity of this sample of highly exposed subjects
may preclude generalization to less severely exposed groups. Also, we did not
assess criterion G in regard to symptoms causing clinically significant distress
and functional impairment. CONCLUSION: The prevalence of PTSD was quite similar
regardless of diagnostic system. The relatively low concordance between the
diagnoses has implications for eligibility for a diagnosis of PTSD.
PMID- 25129533
TI - Long-term Tai Chi training is related to depressive symptoms among Tai Chi
practitioners.
AB - BACKGROUND: Due to the close association with physical and psychological health
and quality of life, mood disorders, especially depressive symptoms, are an
important global public-health issue. It is hypothesized that long-term physical
training and mood adjustment may have a beneficial effect on the prevention of
the onset of depressive symptoms. The aim of this study was to investigate the
relationship between long-term Tai Chi training and depressive symptoms among Tai
Chi practitioners. METHODS: This study analyzed a cross-sectional survey
including 529 Japanese Tai Chi practitioners. Tai Chi training information,
including total training time and a Tai Chi grade, was assessed using a
structured questionnaire, and depressive symptoms were evaluated using the 15
item Geriatric Depression Scale (GDS) for subjects aged >=65 and the 20-item Self
rating Depressive Scale (SDS) for subjects aged <65 with cut-off points: GDS >=5
and SDS >=11. RESULTS: The prevalence of depressive symptoms was 15.9%. After
adjustments for potential confounding factors, the odds ratios of having
depressive symptoms by increasing levels of Tai Chi training time were 1.00, 0.64
(0.37-1.11), 0.65 (0.37-1.13), 0.34 (0.18-0.65) (P for trend <0.01). LIMITATIONS:
This is a cross-sectional study, and not for making a clinical diagnosis of
depressive symptoms. CONCLUSIONS: This study has demonstrated that long-term Tai
Chi training is independently related to a lower prevalence of depressive
symptoms. These results suggest that long-term Tai Chi training may have a
beneficial effect on the prevention of depressive symptoms. Further studies are
needed to confirm these findings.
PMID- 25129535
TI - Long-term outcomes of intrastromal corneal ring segment implantation for post
LASIK ectasia.
AB - PURPOSE: To report the long-term results of intrastromal corneal ring segments
(ICRS) for postoperative LASIK ectasia. METHOD: In this retrospective
interventional cases series, 8 eyes of 6 patients who underwent femtosecond laser
assisted ICRS implantation for post-LASIK ectasia were enrolled. Main outcome
measures were uncorrected distance visual acuity (UDVA), corrected distance
visual acuity (CDVA), spherical equivalent refraction, and average keratometry
(Kavg) values were assessed. RESULTS: Mean+/-SD follow-up was 67+/-21 months
(range, 36-96 months). The mean UDVA, CDVA, spherical equivalent refraction, and
Kavg values were significantly improved at all postoperative visits when compared
to baseline values. No serious complications were observed during follow-up.
CONCLUSION: Our long-term findings showed that ICRS yielded improvements in
visual acuity, refractive status, and keratometric values without any progression
in cases with post-LASIK corneal ectasia.
PMID- 25129536
TI - Spectral transmittance of UV-blocking soft contact lenses: a comparative study.
AB - BACKGROUND: Three major parts of sunlight consist of visible, ultraviolet and
infrared radiation. Exposure to ultraviolet radiation (UVR) can result in a
spectrum of skin and ocular diseases. UV-blocking contact lenses help provide
protection against harmful UV radiation. We studied the ultraviolet and visible
light rays transmission in some soft UV-blocking contact lenses. MATERIAL AND
METHODS: Four available tinted soft lenses (Acuvue Moist, Zeiss CONTACT Day 30
Air spheric, Pretty Eyes and Sauflon 56 UV) have been evaluated for UV and
visible transmission. One-way ANOVA testing was performed to establish is there a
statistically significant difference between the UV regions and visible spectra
means for the contact lenses (alpha=0.05). RESULTS: Pretty Eyes, Zeiss CONTACT,
Acuvue Moist and Sauflon 56 UV showed UV-B transmittance value of 0.65%, 10.69%,
1.22%, and 5.78%, respectively. Pretty Eyes and Acuvue Moist had UV-A
transmittance values of 32% and 34%, Sauflon 56 UV and Zeiss CONTACT had
transmittance values of 48% and 43%, respectively. All of the studied lenses
transmitted at least 94.6% on the visible spectrum. The results of the one-way
ANOVA statistical analysis show that a statistically significant difference
exists within the group of contact lenses tested for the visible (p<0.001), UV-B
(p<0.001) and UV-A (p<0.001) portions of the spectrum (alpha=0.05). CONCLUSION:
Acuvue Moist has the best UV-blocking property and also visible transmission
between other tested contact lenses in this study.
PMID- 25129537
TI - Revision urethroplasty success is comparable to primary urethroplasty: a
comparative analysis.
AB - OBJECTIVE: To assess the efficacy and complications of revision urethroplasty
compared with urethroplasty-naive controls. MATERIALS AND METHODS: A
retrospective analysis was performed of 534 urethroplasties performed by a single
surgeon from August 2003 to March 2011. Patient age, stricture length, location,
etiology, comorbidities, and type of surgery were recorded. Statistical
comparison between the revision cohort and urethroplasty-naive group were made
using Fisher, chi(2), and unpaired t tests, with significance at P < .05 (2
tailed). The primary outcome was urethral patency assessed by cystoscopy.
Secondary (subjective) outcome measures included erectile dysfunction, pain,
urinary tract infection, or chordee at 6 months. RESULTS: A total of 476 patients
met inclusion criteria with completed cystoscopic follow-up. Previous
urethroplasty had failed in 49 patients (10.3%). Patients undergoing revision
urethroplasty were more likely to have stricture in the penile urethra (22.4%; P
= .001), to have strictures exceeding 4 cm in length (71.4% vs 54.3%; P = .023),
and to require tissue transfer (83.6% vs 65.1%; P = .010). Urethral patency rates
did not differ significantly between naive and revision urethroplasty cohorts,
with a mean follow-up of 49.9 months (94.6% vs 91.8%; P = .518). The revision
group had a higher incidence of chordee (2.7% vs 14.3%; P = .001) and urinary
tract infection (3.5% vs 10.2%; P = .04). The rates of erectile dysfunction,
scrotal pain, lower urinary tract symptoms, and incontinence did not differ
significantly between the 2 groups. CONCLUSION: Revision urethroplasty is an
effective treatment option for recurrent stricture after urethroplasty and is
comparable to results in urethroplasty-naive patients. Patients undergoing
revision urethroplasty are more likely to require tissue transfer and experience
higher rates of chordee and urinary tract infection.
PMID- 25129538
TI - Reply: To PMID 25129537.
PMID- 25129539
TI - Impact of prostatic apical shape and protrusion on early recovery of continence
after robot-assisted radical prostatectomy.
AB - OBJECTIVE: To investigate the impact of prostatic apical shape from preoperative
magnetic resonance imaging on early recovery of urinary continence after robot
assisted radical prostatectomy (RARP). MATERIALS AND METHODS: We reviewed the
records of 1011 patients who underwent RARP at a tertiary center from October
2007 to March 2013. Patients were stratified into 4 different groups by prostatic
apical shapes as shown on preoperative magnetic resonance imaging (groups A-D).
The early recovery of urinary continence was defined as 0 or 1 security pad/d
within 12 weeks after the surgery. The association between early recovery of
continence and various factors was analyzed. RESULTS: Overall, 807 patients
(79.8%) showed early recovery of urinary continence. The numbers of patients in
groups A, B, C, and D were 88 (8.7%), 478 (47.3%), 167 (16.5%), and 278 (27.5%),
respectively. There were no significant differences in the rates of early
recovery of urinary continence between different groups (P = .257). On
multivariate analysis, the patient's age (odds ratio [OR], 0.960; P = .004),
preoperative International Index of Erectile Function-5 score (OR, 1.029; P =
.009), neurovascular bundle preservation (OR, 1.586; P = .013), and membranous
urethral length (OR, 1.104; P = .001) were revealed as independent prognostic
factors in the early recovery of urinary continence. CONCLUSION: The results of
our study showed that the prostatic apical shape does not influence the early
recovery of urinary continence. We believe this is another strong point of RARP
compared with conventional open surgery, particularly for patients with complex
type of apical shape.
PMID- 25129540
TI - Clinical value of transurethral second resection of bladder tumor: systematic
review.
AB - OBJECTIVE: To systematically review prospective trials aimed at the role of
restaging transurethral resection (reTUR) to define the group of patients with
bladder cancer who would benefit. MATERIALS AND METHODS: A systematic review of
the literature in accordance with the Preferred Reporting Items for Systematic
Reviews and Meta-analysis guidelines was conducted. RESULTS: Of 120 trials, 7 met
the inclusion criteria. Most studied populations were high-risk non-muscle
invasive bladder cancer patients. Low-risk cancers as well as muscle-invasive
disease were analyzed in only 1 trial. Consistently through the publications,
reTUR improved staging with the rates of muscle-invasive disease mounting to
17.6% when primary resection was deemed to be complete. Although all trials
corroborated staging role of reTUR, only 4 provided recurrence and progression
outcomes, the first being significantly lower in the group of second early
resection. In 2 studies with the longest follow-up and the greatest number of
patients with high-risk non-muscle-invasive bladder cancer, progression rates
were found to be improved. In one trial, reTUR was associated with better
response to bacille Calmette-Guerin. CONCLUSION: The data convincingly suggest
that early second resection improves staging and reduces the recurrence as well
as progression rates of high-risk bladder tumors. reTUR brings benefit to those
subjected to bacille Calmette-Guerin. However, additional surgery would not
modify treatment plan in those with low-risk disease.
PMID- 25129541
TI - Editorial comment.
PMID- 25129542
TI - The association between testicular microlithiasis and semen parameters in Chinese
adult men with fertility intention: experience of 226 cases.
AB - OBJECTIVE: To investigate the association between testicular microlithiasis (TM)
and semen parameters in Chinese adult men with fertility intention. MATERIALS AND
METHODS: We retrospectively reviewed the ultrasonography results of the
reproductive system of 16,204 consecutive adult male patients in our hospital
with fertility intention from November 2012 to October 2013. TM was diagnosed by
scrotal ultrasonography. Patients with TM were divided into classic testicular
microlithiasis (CTM) or limited testicular microlithiasis (LTM). The clinical
data of CTM, LTM, and non-TM groups, especially of patients in whom sperms were
found in semen analysis, were collected and analyzed. RESULTS: There were 226 men
(1.39%) diagnosed with TM. The mean age was 28.96 +/- 5.12 years (range, 21-46
years), whereas mean testicular volume was 15.38 +/- 4.90 mL (range, 1.62-31.23
mL). CTM and LTM were detected in 141 (62.39%) and 85 patients (37.61%),
respectively. Among 200 patients who underwent semen analysis, sperms were found
in 159 men (79.5%; 97 men with CTM and 62 men with LTM). One hundred and twenty
cases without TM (ie, non-TM group) were collected in the control group. Sperm
concentration, total motility, and percentage of progressively motile of CTM,
LTM, and non-TM groups was (38.01 +/- 31.58 million/mL vs 52.31 +/- 33.26
million/mL vs 67.16 +/- 36.94 million/mL; P <.001), (46.03 +/- 23.69% vs 55.37 +/
24.16% vs 62.08 +/- 20.45%; P <.001), and (35.88 +/- 20.17% vs 43.15 +/- 21.08%
vs 47.10 +/- 17.84%; P <.001), respectively. CONCLUSION: TM is associated with
worse semen parameters in adult men with fertility intention. The extent of
microlithiasis correlates inversely with semen parameters.
PMID- 25129544
TI - Gonadoblastoma and selected other aspects of gonadal pathology in young patients
with disorders of sex development.
AB - Some patients with disorders of sex development (DSDs), previously known as
intersex disorders, have abnormal gonadal development and an increased risk of
germ cell tumors. Because of their relative rarity, however, many pathologists
are unfamiliar with the morphological findings in the gonads of DSD patients and
their clinical significance. This review concentrates on some of the most common
DSDs where gonadal specimens may come to the attention of pathologists. It
highlights the findings in gonadal dysgenesis, a DSD with a spectrum of clinical,
pathologic, and molecular features but with the shared attributes of having both
Y chromosomal material (even if in very limited amounts) in the gonad and also
having mutations or deletions in genes necessary for normal gonadal development,
mostly in those upstream of the SOX9 gene. This situation results in testicular
tissue lacking normal Sertoli cells, which are now considered an essential
element for the normal maturation of the primordial germ cells that migrate to
the gonad from the embryonic yolk sac. Germ cells with delayed maturation mimic
neoplastic germ cells, but there are both morphological and immunohistochemical
differences. If the gonad having germ cells with delayed maturation also harbors
the TSPY gene on the GBY locus of the Y chromosome, the cells may undergo
neoplastic transformation and result in the distinctive gonadoblastoma, whose
pathologic features are explored at length herein, including its potential for
variant morphologies, such as a "dissecting" pattern. Another important DSD, the
androgen insensitivity syndrome (AIS), is discussed at length, including the
varied appearances of the testis and its distinctive lesions-hamartomas and
Sertoli cell adenomas. The potential for germ cell neoplasia in the partial AIS
is also discussed and contrasted with that of the complete AIS. A third major
topic is ovotesticular DSD (true hermaphroditism). The clinical features and
morphology of this condition are reviewed, including the arrangements of the
tissue components in an ovotestis. Several other DSDs with distinctive gonadal
findings are also considered, including Klinefelter syndrome, 5alpha-reductase
deficiency, 17beta-hydroxysteroid dehydrogenase deficiency, and female
adrenogenital syndrome.
PMID- 25129543
TI - Molecular pathways reflecting poor intrauterine growth are found in Wharton's
jelly-derived mesenchymal stem cells.
AB - STUDY QUESTION: Are molecular pathways reflecting the biology of small for
gestational age (SGA) neonates preserved in umbilical cord-derived mesenchymal
stem cells (MSCs)? SUMMARY ANSWER: MSCs from SGA newborns were found to express
an altered EGR-1-dependent gene network involved in the regulation of cell
proliferation and oxidative stress. WHAT IS KNOWN ALREADY: Individuals with
suboptimal intrauterine development are at greater risk of metabolic diseases
such as type II diabetes, obesity and cardiovascular disease. STUDY DESIGN, SIZE,
DURATION: Umbilical cords (n = 283) from the GUSTO (growing up in Singapore
towards healthy outcomes) birth cohort study, and primary MSC isolates
established from SGA and matched control cases (n = 6 per group), were subjected
to gene expression analysis and candidate genes were studied for functional
validation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Umbilical cord specimens
were derived from babies born at the National University Hospital (NUH) in
Singapore. Local ethical approval was obtained. MSC isolates were established in
Wharton's jelly and molecular analysis was conducted by gene expression
microarrays and RT-PCR. Cells from SGA and control groups were compared in the
presence and absence of insulin and candidate gene function was studied via siRNA
mediated gene knockdown and over-expression experiments in MSCs. MAIN RESULTS AND
THE ROLE OF CHANCE: Using repeated measure ANOVAs, proliferation rates of MSCs
isolated from SGA neonates were found to be significantly increased (P < 0.01).
In the absence of insulin, EGR-1 levels were found to be significantly reduced in
the group of SGA-derived MSCs, whereas EGR-1 expression was found to be up
regulated in the same group in the presence of insulin (P < 0.01). EGR-1 was
found to induce expression of COX-2 in the SGA group (P < 0.01) and both, EGR-1
and COX-2 stimulated glucose uptake in MSCs (P < 0.01). EGR-1 and COX-2 levels
were associated in whole umbilical cords (n = 283, P < 0.01) and EGR-1 positively
correlated with abdominal circumference and birthweight (n = 91, P < 0.01 and n =
91, P < 0.01). LIMITATIONS, REASONS FOR CAUTION: Cell models may not entirely
reflect the physiology of the host and patient follow-up studies will be
necessary for further clinical validation. WIDER IMPLICATIONS OF THE FINDINGS:
Our study suggests that Wharton's jelly-derived MSCs are useful in identifying
pathways specific for fetal growth restriction. STUDY FUNDING/COMPETING
INTERESTS: This work is supported by the Translational Clinical Research (TCR)
Flagship Program on Developmental Pathways to Metabolic Disease funded by the
National Research Foundation (NRF) and administered by the National Medical
Research Council (NMRC), Singapore- NMRC/TCR/004-NUS/2008'. SICS Investigators
are supported through the Agency for Science Technology and Research (A*STAR)
funding. No potential conflicts of interest relevant to this article were
reported.
PMID- 25129545
TI - The Santa Pola saltern as a model for studying the microbiota of hypersaline
environments.
AB - Multi-pond salterns constitute an excellent model for the study of the microbial
diversity and ecology of hypersaline environments, showing a wide range of salt
concentrations, from seawater to salt saturation. Accumulated studies on the
Santa Pola (Alicante, Spain) multi-pond solar saltern during the last 35 years
include culture-dependent and culture-independent molecular methods and
metagenomics more recently. These approaches have permitted to determine in depth
the microbial diversity of the ponds with intermediate salinities (from 10%
salts) up to salt saturation, with haloarchaea and bacteria as the two main
dominant groups. In this review, we describe the main results obtained using the
different methodologies, the most relevant contributions for understanding the
ecology of these extreme environments and the future perspectives for such
studies.
PMID- 25129546
TI - Gamma knife radiosurgery for the treatment of gynecologic malignancies
metastasizing to the brain: clinical article.
AB - Gynecologic malignancies represent some of the commonest causes of cancer in the
female population. Despite their overall high prevalence, gynecologic
malignancies have seldom been reported to metastasize to the brain. The incidence
of gynecologic cancers spreading to the brain has been rising, and the optimal
management of these patients is not well defined. A retrospective analysis of
patients treated over the past ten years with gamma knife radiosurgery (GKRS) for
metastatic gynecologic cancer to the brain was performed. Radiographic treatment
response, tumor control, metastatic disease progression and survival data were
analyzed. Eight patients with ovarian cancer, six patients with endometrial
cancer and two separates who carried a diagnosis of cervical cancer or
leiomyosarcoma harbored metastatic disease to the brain that was treated with
GKRS. The median dose to the tumor margin was 20 Gy (range 10-22 Gy), and the
median maximum radiosurgical dose was 31 Gy (range 16-52.9 Gy). Tumor control was
achieved in all patients who had follow up imaging studies. Patients with ovarian
cancer had prolonged median survival following GKRS compared to patients with
endometrial cancer (22.3 vs 8.3 months, p = 0.02). The patient with cervical
cancer survived 8 months following her GKRS in the setting of metastatic brain
tumor progression, whereas the patient with leiomyosarcoma passed away within
several weeks of treatment secondary to disseminated extracranial primary
disease. GKRS is a safe and effective means of achieving intracranial tumor
control for patients with gynecologic cancer that has spread to the brain.
PMID- 25129547
TI - Incidence of medulloblastoma in Canadian children.
AB - Medulloblastoma is the most common malignant brain tumor in children. There was a
perception of pediatric neuro-oncologists that the incidence had declined in
Canada. An epidemiological survey was undertaken to determine the incidence of
this tumor in Canada and if a change had indeed occurred. All patients 14 years
and under diagnosed with medulloblastoma from 1990 to 2009 inclusive in Canada
were included. Data collected included date of diagnosis, age at diagnosis,
gender, stage, pathology, treatment, recurrence and current status. Data were
analysed for change in incidence over time. Data were obtained on 574 eligible
patients. The mean overall incidence per 1,000,000 persons was 4.82 (95 % CI 4.28
5.35) for the study time period. The mean age at diagnosis was 5.8 years, and
there was a male predominance. Although there was an increase in incidence over
the first three time periods (24 % for 1990-1994, 27.5 % for 1995-1999, 27.7 %
for 2000-2004), the most recent time period (2005-2009) showed a decrease (21 %).
This was true for male children while the incidence was stable for females. The
mean incidence rate was double for children under the age of 5 years (7.92 per
million) compared to those over 5 years (3.64 per million).This study showed that
from 1990 to 2009 the incidence of medulloblastoma was relatively stable, with a
slight decrease in the last five-year time period.
PMID- 25129548
TI - Social vulnerability from a social ecology perspective: a cohort study of older
adults from the National Population Health Survey of Canada.
AB - BACKGROUND: Numerous social factors, generally studied in isolation, have been
associated with older adults' health. Even so, older people's social
circumstances are complex and an approach which embraces this complexity is
desirable. Here we investigate many social factors in relation to one another and
to survival among older adults using a social ecology perspective to measure
social vulnerability among older adults. METHODS: 2740 adults aged 65 and older
were followed for ten years in the Canadian National Population Health Survey
(NPHS). Twenty-three individual-level social variables were drawn from the 1994
NPHS and five Enumeration Area (EA)-level variables were abstracted from the 1996
Canadian Census using postal code linkage. Principal Component Analysis (PCA) was
used to identify dimensions of social vulnerability. All social variables were
summed to create a social vulnerability index which was studied in relation to
ten-year mortality. RESULTS: The PCA was limited by low variance (47%) explained
by emergent factors. Seven dimensions of social vulnerability emerged in the most
robust, yet limited, model: social support, engagement, living situation, self
esteem, sense of control, relations with others and contextual socio-economic
status. These dimensions showed complex inter-relationships and were situated
within a social ecology framework, considering spheres of influence from the
individual through to group, neighbourhood and broader societal levels. Adjusting
for age, sex, and frailty, increasing social vulnerability measured using the
cumulative social vulnerability index was associated with increased risk of
mortality over ten years in a Cox regression model (HR 1.04, 95% CI:1.01-1.07, p
= 0.01). CONCLUSIONS: Social vulnerability has important independent influence on
older adults' health though relationships between contributing variables are
complex and do not lend themselves well to fragmentation into a small number of
discrete factors. A social ecology perspective provides a candidate framework for
further study of social vulnerability among older adults.
PMID- 25129550
TI - alpha-linolenic acid concentration and not wounding per se is the key regulator
of octadecanoid (oxylipin) pathway activity in rice (Oryza sativa L.) leaves.
AB - Using an in vitro system composed of crushed leaf tissues to simulate the
wounding response in rice leaves, we established that synthesis of jasmonic acid
(JA) and jasmonic acid-isoleucine (JA-Ile) can only occur in unwounded tissue
and, in wounded tissue, that only the chloroplast-located section of the
octadecanoid pathway is active, resulting in the accumulation of 12-oxo
phytodienoic acid (OPDA). We further showed that OPDA accumulation in vitro was
inhibited by 90% using the general lipase inhibitor, tetrahydrolipstatin,
indicating that production of alpha-linolenic acid was the rate-limiting step in
octadecanoid pathway activity in rice following wounding and the enzyme capacity
for an active pathway was already present. We confirmed this result by showing
that added alpha-linolenic acid stimulated OPDA synthesis in vitro and stimulated
OPDA, JA and JA-Ile synthesis in vivo in unwounded tissue. Thus, the response to
wounding can be mimicked by the provision of free alpha-linolenic acid. Our
results draw attention to the key importance of lipase activity in initiation of
JA and JA-Ile biosynthesis and our lack of knowledge of the cognate lipase(s),
lipase substrate identity and mechanism(s) of activation in wounded and unwounded
tissue.
PMID- 25129549
TI - Influence of carotid artery stenting on cognition of elderly patients with severe
stenosis of the internal carotid artery.
AB - BACKGROUND: The aim of this study was to investigate the influence of carotid
artery stenting (CAS) on the cognition and quality of life of elderly patients
with severe stenosis of the internal carotid artery. MATERIAL/METHODS: 65 elderly
patients with symptomatic severe stenosis of internal carotid artery were
recruited into 2 groups: the pharmacotherapy group (n=29) and the CAS group
(n=36). Before surgery and 1, 3, 6, and 12 months after surgery, Montreal
cognitive assessment (MoCA) was used for the evaluation of cognition and WHOQOL
BREF was used for the assessment of quality of life. RESULTS: At 12 months after
surgery, total MoCA score and WHOQOL-BREF score in the pharmacotherapy group was
significantly reduced when compared with those before surgery (P<0.05). In the
CAS group, the total MoCA score, scores of attention and delayed recall, and
WHOQOL-BREF score increased significantly at different time points after surgery
when compared with those before surgery (P<0.05). Moreover, in CAS group, the
MoCA score and WHOQOL-BREF markedly increased gradually over time (P<0.05).
Compared with the pharmacotherapy group, cognition and quality of life in the CAS
group were improved dramatically during the follow-up period (P<0.05).
CONCLUSIONS: Severe stenosis of the internal carotid artery is a cause of
cognition impairment, and CAS may improve cognition and quality of life.
PMID- 25129551
TI - Prospective, randomized, controlled, and open study in primarily inoperable,
stage III non-small cell lung cancer (NSCLC) patients given sequential
radiochemotherapy with or without epoetin alfa.
AB - BACKGROUND AND PURPOSE: Induction chemotherapy is associated with anemia in non
small cell lung cancer (NSCLC) patients undergoing radiotherapy. This randomized,
open-label study compared the effect of sequential radiochemotherapy (RCHT)
versus RCHT + epoetin alfa (RCHT + EPO), with respect to 2-year overall survival
(OS). MATERIAL AND METHODS: Patients ?18 years received sequential RCHT; one arm
also received EPO (chemotherapy day 1, when Hb<12 g/dL). Kaplan-Meier analysis
with log-rank test, and Cox-regression methods were performed. RESULTS: Of the
385 patients randomized (RCHT + EPO: n = 195; RCHT: n = 190), 78 (RCTH + EPO: 46
[23.6%]; RCHT: 32 [16.8%]) were anemic at baseline. Two-year OS was higher in
RCHT + EPO-treated versus RCHT-treated (28.5% [95% CI: 22.2-35.1%] versus 20.6%
[95% CI: 15.1-26.8%] [p = 0.2278]), and requirement for RBC transfusion was lower
(24/195 [12.3%] versus 61/190 [32.1%]). In anemic (baseline) patients (post hoc
analysis), median survival was shorter in RCTH-treated (212 days) versus RCHT +
EPO-treated (343 days) (Hazard ratio = 1.62 [95% CI: 0.99-2.63], p = 0.0525).
Adverse events were documented in 72.7% (RCHT + EPO: 75.0%; RCHT: 70.5%)
patients, and thrombovascular events (TVEs) in 45 patients (RCHT + EPO: 16.7%;
RCHT: 7.9%; p = 0.0099). CONCLUSIONS: A statistically non-significant trend for 2
year OS was observed in a sub-group of EPO-treated NSCLC-patients with baseline
anemia, although this trend was not maintained in the overall population with
inoperable NSCLC.
PMID- 25129552
TI - Laparoscopic repair for failed antireflux procedures.
AB - BACKGROUND: Minimally invasive procedures have become common, and more
reoperations for failed antireflux procedures are performed laparoscopically. We
wanted to study the outcomes of laparoscopic reoperations for reflux. METHODS:
Medical records of all patients who underwent reoperation without esophageal
resection after previous antireflux procedures between January 2000 and October
2012 were reviewed. RESULTS: Seventy-five patients were included in this report:
56 (77%) women and 19 (23%) men. Median age was 58 years. The previous operation
was laparoscopic antireflux procedures in 65 (87%) patients. The median interval
between the last antireflux procedure and laparoscopic reoperation was 42 months.
The median body mass index (BMI) was 28.7. All patients were symptomatic.
Intraoperative findings included recurrent hiatal hernia in 47 (63%) patients,
incompetent fundoplication in 14 (19%) patients, tight fundoplication in 8 (11%)
patients, and tight crura in 2 (3%) patients. Laparoscopic Nissen fundoplication
was performed in 57 (76%) patients, partial posterior fundoplication was
performed in 12 (16%) patients, partial anterior fundoplication was performed in
3 (4%) patients, removal of crural stitches was performed in 2 patients, and a
combination of partial posterior fundoplication and removal of crural stiches was
performed in 1 patient. Complications occurred in 13 (15%) patients. Improvement
in symptoms was observed in 70 (93%) patients in early postoperative follow-up
and in 59 (78%) patients in long-term follow-up. Functional results were
classified as excellent in 59 (78%) patients, good in 6 (7%) patients, fair in 7
(8%) patients, and poor in 3 (4%) patients. CONCLUSIONS: Laparoscopic reoperation
for failed antireflux operations is a complex procedure, but it is safe and
effective in selected patients. Reoperation after a failed antireflux repair
results in excellent or good functional status in a majority of patients, but
these results may deteriorate over time.
PMID- 25129553
TI - Pathogenic vibrios in environmental, seafood and clinical sources in Germany.
AB - Bacteria of the family Vibrionaceae naturally occur in marine and estuarine
environments. Only few species of Vibrionaceae are associated with human cases of
gastroenteritis, ear and wound infections, caused by ingestion of seafood or
contact with Vibrio containing water. Increasing consumption of seafood (fish,
fishery products and shellfish) poses a possible source of Vibrio infections in
Germany. Additionally, there is a growing concern that abundances of pathogenic
vibrios may increase in German coastal waters as a result of e.g. climate change
resulting in probably rising surface water temperatures. According to the One
Health concept the VibrioNet consortium started in 2010 to investigate the
occurrence and relevance of non-cholera vibrios of human concern in Germany.
Vibrios from environmental, seafood and clinical sources were analyzed with the
aim to find connections between different reservoirs or sources and to identify
potential ways of transmission of these pathogens to assess the risk of
infections associated with them. Potentially pathogenic strains mostly belong to
the species Vibrio parahaemolyticus, Vibrio vulnificus and non-O1/non-O139 Vibrio
cholerae. Investigations on imported seafood and mussels from primary production
areas confirmed the frequent occurrence of these species. Moreover, studies of
German coastal waters and sediments showed the presence and seasonality of these
marine bacteria. So far the incidence of clinical cases of vibriosis in Germany
is low. Between 1994 and 2013 thirteen cases of Vibrio spp. associated wound
infections and/or septicaemia have been reported. However, the high prevalence of
vibrios in aquatic environments and aquatic organisms is of concern and demands
continued control of food and surveillance for clinical infections with
pathogenic vibrios.
PMID- 25129555
TI - Staphylococcus aureus isolates from chronic osteomyelitis are characterized by
high host cell invasion and intracellular adaptation, but still induce
inflammation.
AB - Osteomyelitis is a severe inflammatory disease of the bone that is mainly caused
by Staphylococcus aureus. Particularly, bone infections are difficult to treat
and can develop into a chronic course with a high relapsing rate despite of
antimicrobial treatments. The complex interaction of staphylococci with osseous
tissue and the bacterial ability to invade host cells are thought to determine
the severity of infection. Yet, defined bacterial virulence factors responsible
for the pathogenesis of osteomyelitis have not been clearly identified. The aim
of this study was to detect S. aureus virulence factors that are associated with
osteomyelitis and contribute to a chronic course of infection. To this purpose,
we collected 41 S. aureus isolates, each 11 from acute osteomyelitis (infection
period less than 2 months), 10 from chronic osteomyelitis (infection period more
than 12 months), 10 from sepsis and 10 from nasal colonization. All isolates were
analyzed for gene expression and in functional in-vitro systems. Adhesion assays
to bone matrix revealed that all isolates equally bound to matrix structures, but
invasion assays in human osteoblasts showed a high invasive capacity of chronic
osteomyelitis isolates. The high invasion rate could not be explained by defined
adhesins, as all infecting strains expressed a multitude of adhesins that act
together and determine the level of adhesion. Following host cell invasion
isolates from chronic osteomyelitis induced less cytotoxicity than all other
isolates and a higher percentage of Small-colony-variant (SCV)-formation, which
represents an adaptation mechanism during long-term persistence. Isolates from
acute and chronic osteomyelitis strongly produced biofilm and highly expressed
agr and sarA that regulate secreted virulence factors and induced an inflammatory
response in osteoblasts. In conclusion, chronic osteomyelitis isolates were
characterized by a high host cell invasion rate, low cytotoxicity and the ability
to persist and adapt within osteoblasts. Furthermore, isolates from both acute
and chronic osteomyelitis strongly produced biofilm and induced high levels of
host cell inflammation, which may explain tissue destruction and bone deformation
observed as typical complications of long-lasting bone infections.
PMID- 25129554
TI - In vitro and in vivo cell invasion and systemic spreading of Mycoplasma
agalactiae in the sheep infection model.
AB - Generally regarded as extracellular pathogens, molecular mechanisms of mycoplasma
persistence, chronicity and disease spread are largely unknown. Mycoplasma
agalactiae, an economically important pathogen of small ruminants, causes chronic
infections that are difficult to eradicate. Animals continue to shed the agent
for several months and even years after the initial infection, in spite of long
antibiotic treatment. However, little is known about the strategies that M.
agalactiae employs to survive and spread within an immunocompetent host to cause
chronic disease. Here, we demonstrate for the first time its ability to invade
cultured human (HeLa) and ruminant (BEND and BLF) host cells. Presence of
intracellular mycoplasmas is clearly substantiated using differential
immunofluorescence technique and quantitative gentamicin invasion assays.
Internalized M. agalactiae could survive and exit the cells in a viable state to
repopulate the extracellular environment after complete removal of extracellular
bacteria with gentamicin. Furthermore, an experimental sheep intramammary
infection was carried out to evaluate its systemic spread to organs and host
niches distant from the site of initial infection. Positive results obtained via
PCR, culture and immunohistochemistry, especially the latter depicting the
presence of M. agalactiae in the cytoplasm of mammary duct epithelium and
macrophages, clearly provide the first formal proof of M. agalactiae's capability
to translocate across the mammary epithelium and systemically disseminate to
distant inner organs. Altogether, the findings of these in vitro and in vivo
studies indicate that M. agalactiae is capable of entering host cells and this
might be the strategy that it employs at a population level to ward off the host
immune response and antibiotic action, and to disseminate to new and safer niches
to later egress and once again proliferate upon the return of favorable
conditions to cause persistent chronic infections.
PMID- 25129556
TI - A motion-compensated image filter for low-dose fluoroscopy in a real-time tumor
tracking radiotherapy system.
AB - In the real-time tumor-tracking radiotherapy system, a surrogate fiducial marker
inserted in or near the tumor is detected by fluoroscopy to realize respiratory
gated radiotherapy. The imaging dose caused by fluoroscopy should be minimized.
In this work, an image processing technique is proposed for tracing a moving
marker in low-dose imaging. The proposed tracking technique is a combination of a
motion-compensated recursive filter and template pattern matching. The proposed
image filter can reduce motion artifacts resulting from the recursive process
based on the determination of the region of interest for the next frame according
to the current marker position in the fluoroscopic images. The effectiveness of
the proposed technique and the expected clinical benefit were examined by phantom
experimental studies with actual tumor trajectories generated from clinical
patient data. It was demonstrated that the marker motion could be traced in low
dose imaging by applying the proposed algorithm with acceptable registration
error and high pattern recognition score in all trajectories, although some
trajectories were not able to be tracked with the conventional spatial filters or
without image filters. The positional accuracy is expected to be kept within +/-2
mm. The total computation time required to determine the marker position is a few
milliseconds. The proposed image processing technique is applicable for imaging
dose reduction.
PMID- 25129558
TI - No sliding, no pneumothorax: thoracic ultrasound is not an all-purpose tool.
PMID- 25129559
TI - West Nile virus infection and postoperative neurological symptoms: a case report
and review of the literature.
AB - The incidence of West Nile virus, which may cause a range of clinical
presentations including subclinical infections, mild febrile illness, meningitis,
or encephalitis, has increased over recent years. Rare complications, including
optic neuritis, also have been reported. A patient who presented with
preoperative asymptomatic West Nile virus developed fever, altered mental status
and temporary vision loss after elective multilevel spine fusion surgery.
PMID- 25129560
TI - Quality of life after housing first for adults with serious mental illness who
have experienced chronic homelessness.
AB - This 1-year longitudinal study of adults who have recently transitioned from
homelessness to Permanent Supportive Housing (PSH) focuses on quality of life as
a primary outcome of interest. Eighty of 103 new tenants participated in
structured interviews at the time of entry into their new home and at 12-months
post-housing. t-tests assessed differences in community participation and quality
of life measures at the 2 time points. Mixed effects models examined the impact
of community participation on quality of life. Results show that time in
independent housing was significantly associated with several domains of quality
of life. Symptom severity was also significantly and negatively related to
quality of life domains. Community participation was significantly related to
frequency of social contacts only. These findings suggest that community
participation is not critical to improving quality of life, and that despite
concerns that individuals may feel isolated and lonely when living independently,
satisfaction with one's living situation and family relationships nevertheless
improves with housing tenure.
PMID- 25129557
TI - Neoadjuvant capecitabine, bevacizumab and radiotherapy for locally advanced
rectal cancer: results of a single-institute Phase I study.
AB - The aim of this Phase I clinical trial was to assess the feasibility and safety
of capecitabine-based preoperative chemoradiotherapy (CRT) combined with
bevacizumab and to determine the optimal capecitabine dose for Japanese patients
with locally advanced rectal cancer. Patients with cT3/T4 rectal cancer were
eligible. Bevacizumab was administered at 5 mg/kg intravenously on Days 1, 15 and
29. Capecitabine was administered on weekdays concurrently with pelvic
radiotherapy at a daily dose of 1.8 Gy, totally to 50.4 Gy. Capecitabine was
initiated at 825 mg/m(2) twice daily at Dose Level 1, with a planned escalation
to 900 mg/m(2) twice daily at Dose Level 2. Within 6.1-10.3 (median, 9.4) weeks
after the completion of the CRT, surgery was performed. Three patients were
enrolled at each dose level. Regarding the CRT-related acute toxicities, all of
the adverse events were limited to Grade 1. There was no Grade 2 or greater
toxicity. No patient needed attenuation or interruption of bevacizumab,
capecitabine or radiation. All of the patients received the scheduled dose of
CRT. All of the patients underwent R0 resection. Two (33.3%) of the six patients
had a pathological complete response, and five (83.3%) patients experienced
downstaging. In total, three patients (50%) developed postoperative
complications. One patient developed an intrapelvic abscess and healed with
incisional drainage. The other two patients healed following conservative
treatment. This regimen was safely performed as preoperative CRT for Japanese
patients with locally advanced rectal cancer. The recommended capecitabine dose
is 900 mg/m(2) twice daily.
PMID- 25129561
TI - Monitoring mood states in everyday life: a new device for patients with
cerebellar ataxia.
AB - Thirty patients with cerebellar ataxia and 40 healthy volunteers underwent 7 days
of mood monitoring using a new device requiring a low motor load. Its convergent
validity and compliance were tested. The measurements resulted consistent with
validated scale scores. Patients' motor impairment did not affect the compliance.
PMID- 25129562
TI - Effectiveness and clinical predictors of response to combined ECT and
antipsychotic therapy in patients with treatment-resistant schizophrenia and
dominant negative symptoms.
AB - The effectiveness and predictors of response to electroconvulsive therapy (ECT)
combined with antipsychotics (AP) in treatment-resistant schizophrenia patients
with the dominance of negative symptoms (TRS-NS) have not been studied
systematically so far. 29 patients aged 21-55 years diagnosed with TRS-NS
underwent ECT combined with antipsychotics (ECT+AP). Prior to the ECT, the
symptom profile and severity were evaluated using Positive and Negative Syndrome
Scale (PANSS). Demographic and medical data was collected; ECT parameters and
pharmacotherapy results were evaluated. After the combined ECT+AP therapy a
significant decrease in symptom severity was found. A response to treatment was
achieved by 60% of patients. The greatest reductions were obtained in general and
positive PANSS subscale (median change: 11 and 7 pts.) and the smallest, but
still significant, ones in negative symptoms subscale (median: 3.5 pts.).
Patients who responded to ECT+AP demonstrated a significantly shorter duration of
the current episode in comparison with patients who did not experience at least a
25% reduction in symptom severity (median: 4 vs. 8 months). A combination of ECT
and antipsychotic therapy can provide a useful treatment option for patients with
TRS-NS. The only significant predictor of response to treatment was a shorter
duration of the current episode.
PMID- 25129563
TI - Effects of mood state on divided attention in patients with bipolar disorder:
evidence for beneficial effects of subclinical manic symptoms.
AB - A relatively small number of studies have been dedicated to the differential
effects of the current mood state on cognition in patients with a bipolar
disorder (BD). The aim of the current study was to investigate the effect of
current mood state on divided attention (DA) performance, and specifically
examine possible beneficial effects of the (hypo-) manic state. Over a maximum
period of 24 months, medication use, divided attention test (a subtest of the
Test for Attentional Performance (TAP)) was assessed every 6 months in 189
outpatients with BD. Data were analyzed with multilevel regression analysis (i.e.
linear mixed models). DA performance varied considerable over time within
patients. Corrected for psychotropic medication a significant quadratic
relationship between manic symptoms and DA performance was found, with mild
hypomanic symptoms having a positive influence on divided attention scores and
moderate to severe manic symptoms having a negative influence. No association
between depressive symptoms and DA performance was found. In future research on
mania and cognition as well as in the clinical practice both the beneficial and
negative effects of mania should be taken into account.
PMID- 25129564
TI - Adult offspring perspectives on parental hoarding behaviors.
AB - Hoarding disorder (HD) is characterized by difficulty discarding unneeded items
and the accumulation of items within living spaces and is associated with
significant functional impairment and distress. Along with the negative impact of
hoarding on the individual, HD is substantially impairing for family members, and
linked to disruptions in family functioning. The present study utilized a path
model analysis to examine the associations between an array of hoarding variables
hypothesized to impact family functioning and parent-offspring relationships in
150 adult-aged children of hoarders who responded to online requests to
participate in a research study. It was hypothesized that increased hoarding
severity, decreased insight, and increased family accommodation (i.e., act of
family members facilitating or assisting in hoarding behaviors) would be
associated with decreased family functioning, decreased quality of parent
offspring relationships, and increased offspring impairment. Results from the
path model revealed that family functioning mediated the relationship between
hoarding severity and parent-offspring relationship. Diminished insight in the
hoarding parent (as reported by the offspring) was associated with increased
familial conflict and family functioning partially mediated the relationship
between insight and quality of parent-offspring relationship. Increased family
accommodation was significantly associated with increased impairment (work,
social, and family domains) in offspring of hoarders.
PMID- 25129565
TI - Concordance of the SHEA-IDSA severity classification for Clostridium difficile
infection and the ATLAS bedside scoring system in hospitalized adult patients.
AB - PURPOSE: The Society for Healthcare Epidemiology of America and Infectious
Diseases Society of America (SHEA-IDSA) guidelines for the treatment of
Clostridium difficile infection (CDI) recommend initial treatment of CDI based on
disease severity. This severity definition has not been validated or evaluated
based on clinical outcomes. The ATLAS scoring system is a validated tool useful
in predicting treatment response and mortality in CDI. The main purpose of this
study is to evaluate the concordance of the ATLAS scoring system and the SHEA
IDSA staging for CDI severity. METHODS: This was a retrospective study which
included hospitalized patients with confirmed CDI. Bivariate analyses compared
baseline demographics and clinical information between patients with nonsevere
and severe CDI based on the SHEA-IDSA criteria for CDI severity. Kappa scores
were calculated to compare the concordance of the two scoring systems in defining
CDI severity. Sensitivity and specificity of the ATLAS scoring system to
determine CDI severity were calculated using the SHEA-IDSA criteria as the
reference standard. RESULTS: Sixty-four patients met inclusion criteria. Of
those, 62.5% were classified as mild to moderate CDI, 25% were severe,
uncomplicated, and 12.5% were severe, complicated based on SHEA-IDSA criteria. In
the bivariate analyses, ATLAS score breakpoints of >= 4, >= 5, and >= 6 revealed
moderate agreement with the SHEA-IDSA classification for severity. The
sensitivities and specificities for ATLAS scores in predicting CDI severity
ranged from 58.3 to 87.5, and 67.5-87.5%, respectively. CONCLUSION: The ATLAS
score may be useful in evaluating CDI severity and determining drug therapy
selection.
PMID- 25129566
TI - A case study of enteric virus removal and insights into the associated risk of
water reuse for two wastewater treatment pond systems in Bolivia.
AB - Wastewater treatment ponds (WTP) are one of the most widespread treatment
technologies in the world; however, the mechanisms and extent of enteric virus
removal in these systems are poorly understood. Two WTP systems in Bolivia, with
similar overall hydraulic retention times but different first stages of
treatment, were analyzed for enteric virus removal. One system consisted of a
facultative pond followed by two maturation ponds (three-pond system) and the
other consisted of an upflow anaerobic sludge blanket (UASB) reactor followed by
two maturation (polishing) ponds (UASB-pond system). Quantitative polymerase
chain reaction with reverse transcription (RT-qPCR) was used to measure
concentrations of norovirus, rotavirus, and pepper mild mottle virus, while cell
culture methods were used to measure concentrations of culturable enteroviruses
(EV). Limited virus removal was observed with RT-qPCR in either system; however,
the three-pond system removed culturable EV with greater efficiency than the UASB
pond system. The majority of viruses were not associated with particles and only
a small proportion was associated with particles larger than 180 MUm; thus, it is
unlikely that sedimentation is a major mechanism of virus removal. High
concentrations of viruses were associated with particles between 0.45 and 180 MUm
in the UASB reactor effluent, but not in the facultative pond effluent. The
association of viruses with this size class of particles may explain why only
minimal virus removal was observed in the UASB-pond system. Quantitative
microbial risk assessment of the treated effluent for reuse for restricted
irrigation indicated that the three-pond system effluent requires an additional 1
to 2-log10 reduction of viruses to achieve the WHO health target of <10(-4)
disability-adjusted life years (DALYs) lost per person per year; however, the
UASB-pond system effluent may require an additional 2.5- to 4.5-log10 reduction
of viruses.
PMID- 25129567
TI - Screen-viewing among preschoolers in childcare: a systematic review.
AB - BACKGROUND: Screen-viewing is one of the most common sedentary behaviors among
preschoolers. Despite the high prevalence of sedentary behaviors in childcare,
little research exists on the context and/or type of activities that account for
these particular behaviors. Accordingly, if the amount of screen-viewing
accumulated by preschoolers in childcare is not considered, researchers may be
underestimating total screen time among this population, as only a portion of
their day is being captured (i.e., the home environment). This systematic review
provides a synthesis of research on the levels of screen-viewing among preschool
aged children (2.5-5 years) attending childcare (i.e., centre- and home-based
childcare). This review also examined the correlates of screen-viewing among
preschoolers in this setting. To provide additional contextual information,
availability of screen activities was used to help ameliorate the understanding
of preschoolers' screen-viewing behaviors in childcare. METHODS: Twelve
electronic databases were searched to retrieve relevant articles for inclusion
(dating from 2000 onwards). Additional studies were identified via manual
searching techniques (i.e., hand searching and citation tracking). Only English,
published peer-reviewed articles that examined preschoolers' screen-viewing
behaviors in childcare (i.e., rates of screen-viewing and access to/opportunities
for related activities) were included. No restrictions to study design were
applied. RESULTS: Seventeen international studies (4 experimental; 12 cross
sectional; 1 mixed-methods) published between 2004 and 2014 were examined. Of
those, eight studies reported rates of screen-viewing and found that preschoolers
spent approximately 0.1 to 1.3 hrs/day and 1.8 to 2.4 hrs/day engaged in this
behavior in center- and home-based childcare, respectively. High staff education
(negative association) and type of childcare arrangement (notably, home-based
childcare in comparison to center-based childcare; positive association) were
identified as two correlates in relation to preschoolers' screen-viewing in
childcare. Nine studies spoke to the availability of screen-viewing activities in
childcare, and found the childcare environment to be conducive to this behavior.
CONCLUSIONS: Despite some variability, preschoolers appear to engage in somewhat
high levels of screen-viewing while in childcare, particularly within home-based
facilities. This paper also highlighted the conduciveness of the childcare
environment with regard to screen-viewing among preschoolers. Additional
exploration into the correlates of screen-viewing in childcare is required.
(PROSPORO registration: CRD42013005552).
PMID- 25129568
TI - What can providers learn from childhood body mass index trajectories: a study of
a large, safety-net clinical population.
AB - OBJECTIVE: To describe childhood weight gain using body mass index (BMI) z-score
trajectories in a low-income urban safety-net population and identify among
gender- and race/ethnicity-specific groups any trends for increased risk.
METHODS: A retrospective cohort study was conducted among 2- to 12-year-old
patients (2006-2013) visiting a safety-net provider. BMI z-score trajectories
were calculated overall, for gender- and race/ethnicity-specific groups, and for
peak BMI percentile subgroups to describe weight gain longitudinally. RESULTS:
From 2006 to 2013, a total of 26,234 eligible children were followed for an
average of 3.7 years. At baseline (mean age, 4.2 years), 74% of patients were at
a normal weight compared to 65% at most recent observation (mean age, 7.8 years).
All gender and race/ethnicity subgroups showed increasing average BMI z-scores
during childhood. Children consistently under the 50th percentile and those of
white race had the most stable BMI z-score trajectories. BMI z-score increased
with increasing age in all subgroups. Hispanic boys and black girls had the most
significant increase in BMI z-score during this observation period. Children
observed in early childhood and whose BMI exceeded the 95th percentile at any
time were often already overweight (20%) or obese (36%) by 3 years of age.
CONCLUSIONS: The entire population demonstrated an upward trend in BMI z-score
trajectory. This trend was most notable among black girls and Hispanic boys. Many
obese children were already overweight by age 3, and persistence of obesity after
3 years of age was high, suggesting that intervention before age 3 may be
essential to curbing unhealthy weight trajectories.
PMID- 25129569
TI - The social construction of 'dowry deaths'.
AB - The classification of cause of death is real in its consequences: for the
reputation of the deceased, for her family, for those who may be implicated, and
for epidemiological and social research and policies and practices that may
follow from it. The study reported here refers specifically to the processes
involved in classifying deaths of women from burns in India. In particular, it
examines the determination of 'dowry death', a class used in India, but not in
other jurisdictions. Classification of death is situated within a framework of
special legal provisions intended to protect vulnerable women from dowry-related
violence and abuse. The findings are based on 33 case studies tracked in hospital
in real time, and interviews with 14 physicians and 14 police officers with
experience of dealing with burns cases. The formal class into which any given
death is allocated is shown to result from motivated accounting processes
representing the interests and resources available to the doctors, victims,
victim families, the victim's husband and his family, and ultimately, the police.
These processes may lead to biases in research and to injustice in the treatment
of victims and alleged offenders. Suggestions are made for methods of
ameliorating the risks.
PMID- 25129570
TI - The role of low levels of fullerene C60 nanocrystals on enhanced learning and
memory of rats through persistent CaMKII activation.
AB - Engineered nanomaterials are known to exhibit diverse and sometimes unexpected
biological effects. Fullerene nanoparticles have been reported to specifically
bind to and elicit persistent activation of hippocampal Ca(2+)/calmodulin
dependent protein kinase II (CaMKII), a multimeric intracellular serine/threonine
kinase central to Ca(2+) signal transduction and critical for synaptic
plasticity, but the functional consequence of that modulation is unknown. Here we
show that low doses of fullerene C60 nanocrystals (Nano C60), delivered through
intrahippocampal infusion and without any obvious cytotoxicity in hippocampal
neuronal cells, enhance the long-term potentiation (LTP) of rats. Intraperitoneal
injection of 320 MUg/kg of Nano C60, once daily for 10 days, also enhanced
spatial memory of rats in addition to an increase of LTP. In parallel, both the
IH and IP administration of Nano C60 increased the autonomous activity and the
level of threonine 286 (T286) autophosphorylation of CaMKII, enhanced post
synaptic AMPA/NMDA ratio, and triggered time-dependent activation of ERK and
CREB. Our results reveal a striking and highly unexpected ability of Nano C60 in
positively modulating learning and memory, an effect that is most likely
manifested through locking CaMKII in an active conformation, and may have
significant implications for the potential therapeutic applications of fullerene
C60, a classic engineered nanomaterial.
PMID- 25129571
TI - The mechanism for keratinocyte detaching from pH-responsive chitosan.
AB - In this study, we compared the detachment ratio of HaCaT and Hs68 cells from pH
responsive chitosan surface by raising medium pH from 7.20 to 7.65 for 60 min.
The detachment ratio of elongated Hs68 cells was over 75%, but that of round
shaped HaCaT cells was less than 50%, even extending the incubation time to 6 h
or enhancing the cytoskeletal contractile force with the Rho activator CN01.
However, the addition of 2 mm of EDTA into the medium at pH 7.65 could
effectively detach HaCaT cells (detachment ratio > 90%), indicating that the
calcium ion played an important role in the detachment process. Therefore, the
family of Ca(+2)-dependent integrin receptors was examined by RT-PCR, real-time
PCR and immunocytochemistry. It was found the expression of integrin beta4
(ITGb4) was HaCaT cell-specific and the mRNA level of ITGb4 in undetached HaCaT
cells was significantly higher than that in detached ones. By modulating ITGb4
activity with specific functional blocking antibody ASC-8, the detachment ratio
of HaCaT cells could be increased to be greater than 85%. Conversely, the
addition of the ligand of ITGb4 laminin into the culture system decreased the
medium pH-induced detachment ratio for HaCaT cells, but not for Hs68 cells.
Further addition of ASC-8 could rescue the effect of laminin on preventing the
detachment of HaCaT cells from pH-sensitive chitosan surface. Therefore, this
study demonstrated the interaction of ITGb4 and laminin played an important role
in controlling the detachment of HaCaT cells on pH-responsive chitosan.
PMID- 25129572
TI - Treatment of PTSD and Chronic Daily Headache.
AB - OPINION STATEMENT: Posttraumatic stress disorder (PTSD) is often comorbid with
chronic migraine (CM) and chronic tension-type headache (CTTH). Trauma-focused
cognitive behavioral psychotherapies, selective serotonin reuptake inhibitors
(SSRIs), and venlafaxine have demonstrated efficacy in the treatment of PTSD.
Amitriptyline, topiramate, sodium valproate, and botulinum toxin A are
efficacious for treatment of chronic daily headache (CDH). Treatment studies on
individuals with CDH and comorbid PTSD, however, are limited. As such, multiple
therapeutic agents or modes of interventions typically are necessary, such that
comprehensive treatment simultaneously utilizes approaches with established
efficacy for each individual condition.
PMID- 25129573
TI - Long-term wheel running changes on sensorimotor activity and skeletal muscle in
male and female mice of accelerated senescence.
AB - The senescence-accelerated mouse prone 8 (SAMP8) is considered a useful non
transgenic model for studying aspects of aging. Using SAM resistant 1 (SAMR1) as
controls, the long-term effects of wheel running on skeletal muscle adaptations
and behavioral traits were evaluated in senescent (P8) and resistant (R1) male
and female mice. Long-term wheel running (WR) led to increases in locomotor
activity, benefits in sensorimotor function, and changes in body weight in a
gender-dependent manner. WR increased body weight and baseline levels of
locomotor activity in female mice and improved balance and strength in male mice,
compared to sedentary-control mice. WR resulted in key metabolic adaptations in
skeletal muscle, associated with an increased activity of the sirtuin 1-AMP
activated protein kinase (AMPK)-PGC-1 alpha axis and changes in vascular
endothelial growth factor A (Vegfa), glucose transporter type 4 (Glut4), and
Cluster of Differentiation 36 (Cd36) gene expression. Overall, our data indicate
that activity, balance, and strength decrease with age and that long-term WR may
significantly improve the motor function in a mouse model of senescence in a
gender-dependent manner.
PMID- 25129574
TI - Are the leukocyte telomere length attrition and telomerase activity alteration
potential predictor biomarkers for sporadic TAA in aged individuals?
AB - A large variability in occurrence, complications, and age/gender manifestations
characterizes individual susceptibility of sporadic thoracic aortic aneurysms
(TAA), even in subjects with the same risk factor profiles. The reasons are
poorly understood. On the other hand, TAA pathophysiology mechanisms remain
unclear than those involved in abdominal aorta aneurysms. However, recent
evidence is suggesting a crucial role of biological ageing in inter-individual
risk variation of cardiovascular diseases, including sporadic TAA. Biological age
rather than chronological age is a better predictor of vascular risk. Relevant
assumptions support this concept. In confirming this evidence and our preliminary
data, the mean of blood leukocyte telomere length, through use of terminal
restriction fragment assay and in blood samples from sporadic TAA patients and
controls, was examined. Telomerase activity was also analyzed in two groups. In
addition, we verified the weight of genetic inflammatory variants and the major
TAA risk factors in telomere/telomerase impairment. Aorta histopathological
abnormalities and systemic inflammatory mediators were ultimately correlated with
telomere/telomerase impairment. Data obtained demonstrated shorter telomeres and
a reduced telomerase activity in TAA patients significantly associated with a
genetic inflammatory risk profile, age, gender, smoking, hypertension, a
histopathological phenotype, and higher levels of systemic inflammatory mediators
than controls. In conclusion, telomere and telomerase activity's detection might
be used as predictor biomarkers of sporadic TAA. Their impairment also suggests a
strong role of vascular ageing in sporadic TAA, evocated by both environmental
and genetic inflammatory factors.
PMID- 25129575
TI - Experiences with capnography in acute care settings: a mixed-methods analysis of
clinical staff.
AB - PURPOSE: Although capnography is being incorporated into clinical guidelines, it
is not used to its full potential. We investigated reasons for limited
implementation of capnography in acute care areas and explored facilitators and
barriers to its implementation. METHODS: A purposeful sample of physicians and
nurses in emergency departments and intensive care units participated in
semistructured interviews. Grounded theory, iterative data analysis, and the
constant comparative method were used to analyze the data to inductively generate
ideas and build theories. RESULTS: Nineteen providers were interviewed from 5
hospitals. Six themes were identified: variability in use of capnography among
acute care units, availability and accessibility of capnography equipment, the
evidence behind capnography use, the impact of capnography on patient care,
personal experiences impacting use of capnography, and variable knowledge about
capnography. Barriers and facilitators to use were found within each theme.
CONCLUSIONS: We observed varied responsiveness to capnography and identified
factors that work to foster or discourage its use. These data can guide future
implementation strategies. A deliberate strategy to foster utilization, mitigate
barriers, and broadly accelerate implementation has the potential to profoundly
impact use of capnography in acute care areas with the goal of improving patient
care.
PMID- 25129576
TI - Correlation of patient-reported outcomes of sedation and sedation assessment
scores in critically ill patients.
AB - PURPOSE: Patient-reported outcomes (PROs) are recommended as indicators of
quality in the intensive care unit. We studied the correlation between PROs of
sedation quality and a universal sedation assessment scale in critically ill
patients. MATERIALS AND METHODS: Twenty-nine mechanically ventilated adults
admitted to a surgical/trauma or medical intensive care unit requiring continuous
infusion sedation for 24 hours or more were prospectively included. Patient
reported outcomes were evaluated through sedation questionnaire 24 hours post
continuous infusion sedation. The primary outcome was the correlation of PROs
with Sedation-Agitation Scale (SAS) scores. RESULTS: Mean (SD) SAS scores per 12
hour nursing shift for propofol (n=179), midazolam (n=42), and dexmedetomidine
(n=8) were 3.78 (77), 3.31 (1.1), and 2.98 (0.76), respectively. The mean score
for survey questions addressing perceptions of comfort was 5.3 (1, complete
comfort; 10, not comfortable at all). Of the patients, 34%, 7%, and 52% would
want more, less, or the same amount of sedation, respectively, if this situation
were to arise again. Patient perception of comfort correlated with the percent
time at goal SAS score; r=0.31 (P<.05). CONCLUSION: Patient-reported outcomes of
sedation correlate with the percentage of time spent in the goal range of scores
for a universal sedation assessment scale. These findings represent initial
attempts to appreciate the patient's perspective in the management and monitoring
of agitation.
PMID- 25129577
TI - Aspiration pneumonia: a review of modern trends.
AB - PURPOSE: The purpose was to describe aspiration pneumonia in the context of other
lung infections and aspiration syndromes and to distinguish between the main
scenarios commonly implied when the terms aspiration or aspiration pneumonia are
used. Finally, we aim to summarize current evidence surrounding the diagnosis,
microbiology, treatment, risks, and prevention of aspiration pneumonia. MATERIALS
AND METHODS: Medline was searched from inception to November 2013. All
descriptive or experimental studies that added to the understanding of aspiration
pneumonia were reviewed. All studies that provided insight into the clinical
aspiration syndromes, historical context, diagnosis, microbiology, risk factors,
prevention, and treatment were summarized within the text. RESULTS: Despite the
original teaching, aspiration pneumonia is difficult to distinguish from other
pneumonia syndromes. The microbiology of pneumonia after a macroaspiration has
changed over the last 60 years from an anaerobic infection to one of aerobic and
nosocomial bacteria. Successful antibiotic therapy has been achieved with several
antibiotics. Various risks for aspiration have been described leading to several
proposed preventative measures. CONCLUSIONS: Aspiration pneumonia is a disease
with a distinct pathophysiology. In the modern era, aspiration pneumonia is
rarely solely an anaerobic infection. Antibiotic treatment is largely dependent
on the clinical scenario. Several measures may help prevent aspiration pneumonia.
PMID- 25129578
TI - Bacterial diversity assessment in soil of an active Brazilian copper mine using
high-throughput sequencing of 16S rDNA amplicons.
AB - Mining activities pose severe environmental risks worldwide, generating extreme
pH conditions and high concentrations of heavy metals, which can have major
impacts on the survival of organisms. In this work, pyrosequencing of the V3
region of the 16S rDNA was used to analyze the bacterial communities in soil
samples from a Brazilian copper mine. For the analysis, soil samples were
collected from the slopes (geotechnical structures) and the surrounding drainage
of the Sossego mine (comprising the Sossego and Sequeirinho deposits). The
results revealed complex bacterial diversity, and there was no influence of
deposit geographic location on the composition of the communities. However, the
environment type played an important role in bacterial community divergence; the
composition and frequency of OTUs in the slope samples were different from those
of the surrounding drainage samples, and Acidobacteria, Chloroflexi, Firmicutes,
and Gammaproteobacteria were responsible for the observed difference. Chemical
analysis indicated that both types of sample presented a high metal content,
while the amounts of organic matter and water were higher in the surrounding
drainage samples. Non-metric multidimensional scaling (N-MDS) analysis identified
organic matter and water as important distinguishing factors between the
bacterial communities from the two types of mine environment. Although habitat
specific OTUs were found in both environments, they were more abundant in the
surrounding drainage samples (around 50 %), and contributed to the higher
bacterial diversity found in this habitat. The slope samples were dominated by a
smaller number of phyla, especially Firmicutes. The bacterial communities from
the slope and surrounding drainage samples were different in structure and
composition, and the organic matter and water present in these environments
contributed to the observed differences.
PMID- 25129579
TI - Longitudinal changes of telomere length and epigenetic age related to traumatic
stress and post-traumatic stress disorder.
AB - Several studies have reported an association between traumatic stress and
telomere length suggesting that traumatic stress has an impact on ageing at the
cellular level. A newly derived tool provides an additional means to investigate
cellular ageing by estimating epigenetic age based on DNA methylation profiles.
We therefore hypothesise that in a longitudinal study of traumatic stress both
indicators of cellular ageing will show increased ageing. We expect that
particularly in individuals that developed symptoms of post-traumatic stress
disorder (PTSD) increases in these ageing parameters would stand out. From an
existing longitudinal cohort study, ninety-six male soldiers were selected based
on trauma exposure and the presence of symptoms of PTSD. All military personnel
were deployed in a combat zone in Afghanistan and assessed before and 6 months
after deployment. The Self-Rating Inventory for PTSD was used to measure the
presence of PTSD symptoms, while exposure to combat trauma during deployment was
measured with a 19-item deployment experiences checklist. These groups did not
differ for age, gender, alcohol consumption, cigarette smoking, military rank,
length, weight, or medication use. In DNA from whole blood telomere length was
measured and DNA methylation levels were assessed using the Illumina 450K DNA
methylation arrays. Epigenetic ageing was estimated using the DNAm age estimator
procedure. The association of trauma with telomere length was in the expected
direction but not significant (B=-10.2, p=0.52). However, contrary to our
expectations, development of PTSD symptoms was associated with the reverse
process, telomere lengthening (B=1.91, p=0.018). In concordance, trauma
significantly accelerated epigenetic ageing (B=1.97, p=0.032) and similar to the
findings in telomeres, development of PTSD symptoms was inversely associated with
epigenetic ageing (B=-0.10, p=0.044). Blood cell count, medication and premorbid
early life trauma exposure did not confound the results. Overall, in this
longitudinal study of military personnel deployed to Afghanistan we show an
acceleration of ageing by trauma. However, development of PTSD symptoms was
associated with telomere lengthening and reversed epigenetic ageing. These
findings warrant further study of a perhaps dysfunctional compensatory cellular
ageing reversal in PTSD.
PMID- 25129580
TI - Darwinian medicine and psoriasis.
AB - Darwinian medicine, or evolutionary medicine, regards some pathological
conditions as attempts by the organism to solve a problem or develop defense
mechanisms. At certain stages of human evolution, some diseases may have
conferred a selective advantage. Psoriasis is a high-penetrance multigenic
disorder with prevalence among whites of up to 3%. Psoriatic lesions have been
linked with enhanced wound-healing qualities and greater capacity to fight
infection. Leprosy, tuberculosis, and infections caused by viruses similar to
human immunodeficiency virus have been postulated as environmental stressors that
may have selected for psoriasis-promoting genes in some human populations. The
tendency of patients with severe psoriasis to develop metabolic syndrome may
reflect the body's attempt to react to environmental stresses and warning signs
by triggering insulin resistance and fat storage.
PMID- 25129581
TI - Editor's note.
PMID- 25129582
TI - Clarity of purpose, focused attention: The essence of excellence.
PMID- 25129583
TI - 2014 AATS guidelines for the prevention and management of perioperative atrial
fibrillation and flutter for thoracic surgical procedures. Executive summary.
PMID- 25129584
TI - Aspirin unresponsiveness predicts thrombosis in high-risk pediatric patients
after cardiac surgery.
AB - OBJECTIVE: Thrombosis occurs in up to 26% of patients with congenital heart
disease after cardiac surgery and is associated with increased morbidity and
mortality. Aspirin is commonly administered to reduce the risk of thrombosis, yet
aspirin responsiveness is rarely assessed. In this study, we hypothesize that
inadequate response to aspirin is associated with increased risk of thrombosis
after selected congenital cardiac procedures considered to be high risk for
thrombosis. METHODS: Patients undergoing high-risk congenital cardiac surgery who
received postoperative aspirin (N = 95) were studied. Response to aspirin was
determined using the VerifyNow system several days after administration. Patients
were monitored prospectively for 30 days for the development of a thrombosis
event and the relationship between aspirin unresponsiveness and a thrombosis
event was determined by the Fisher exact test. RESULTS: Rate of aspirin
unresponsiveness (>=550 aspirin reaction units [ARU]) was 10 of 95 (10.5%) and
was highest in patients weighing less than 5 kg given 20.25 mg/d of aspirin.
Thrombosis events occurred in 7 patients (7.4%). Thrombosis was observed in 6 of
10 (60%) patients who were unresponsive to aspirin, compared with 1 of 85 (1.2%)
patients who were responsive to aspirin (P < .001). In 2 patients who were
unresponsive to the initial aspirin dose, an increase in dose resulted in an
adequate therapeutic aspirin response (ARU < 550), suggesting insufficiency
rather than true resistance in a subset of patients. CONCLUSIONS: Postoperative
thrombosis is associated with aspirin unresponsiveness in this patient
population. In high-risk patients, monitoring of aspirin therapy and
consideration of dose adjustment or alternative agents for unresponsive patients
may be justified and warrants further investigation in a prospective trial.
PMID- 25129586
TI - Mechanisms of tricuspid regurgitation in patients with hypoplastic left heart
syndrome undergoing tricuspid valvuloplasty.
AB - OBJECTIVES: Tricuspid regurgitation (TR) remains a risk factor for morbidity and
mortality through staged palliation in patients with hypoplastic left heart
syndrome (HLHS). Reports on the mechanisms associated with TR in patients with
HLHS are limited. Thus, we sought to describe our experience with tricuspid valve
(TV) repair in these patients, focusing on the mechanisms of TR and corresponding
surgical techniques. METHODS: We performed a retrospective single-center review
(January 2000 to December 2012) of patients with HLHS undergoing TV repair and
completing Fontan circulation. We evaluated the pre- and postoperative
echocardiograms, intraoperative findings, and surgical techniques used. RESULTS:
A total of 53 TV repairs were performed in 35 patients with HLHS completing
staged palliation. TV repairs were performed at stage II in 15, between stage II
and III in 4, at stage III in 27, and after stage III in 7. The surgical
techniques for valvuloplasty included annuloplasty (38%), anteroseptal (AS)
commissuroplasty (66%), anterior papillary muscle repositioning (11%), multiple
commissuroplasties (9%), septal-posterior commissuroplasty (9%), and fenestration
closure (4%). The predominant jet of TR emanated along the AS commissure in 68%
of the cases. All patients survived the procedure and were discharged.
Preoperative echocardiography showed a dilated TV annulus on the lateral
dimension, anteroposterior dimension, and area that was significantly reduced
after TV repair (P < .0001). The preoperative mean TR, as assessed by lateral (P
= .002) and anteroposterior (P = .005) vena contracta, was also significantly
reduced after TV repair. TV repair did not significantly affect right ventricular
systolic function immediately after surgery (P = .17) or at the most recent
follow-up visit (P = .52). Patients with anterior leaflet prolapse were at
increased risk of worse outcomes, including moderate or greater right ventricular
dysfunction (P = .02). Patients requiring reoperation for TV repair were younger
(6.3 vs 28.1 months, P < .0001) at the initial operation. One patient died of
heart failure. Freedom from TV replacement and transplant-free survival were both
97% at the most recent follow-up point. CONCLUSIONS: TR in patients with HLHS
commonly emanates from the AS commissure. The associated mechanisms are often
annular dilatation and anterior leaflet prolapse. Preoperative anterior leaflet
prolapse was associated with worse outcomes. Annuloplasty, closure of the AS
commissure, and repositioning of the anterior papillary muscle are effective in
addressing TR in the short- and mid-term in this challenging population.
PMID- 25129589
TI - Pulmonary endarterectomy for distal chronic thromboembolic pulmonary
hypertension.
AB - OBJECTIVES: Chronic thromboembolic pulmonary hypertension can be cured by
pulmonary endarterectomy. Operability assessment remains a major concern, because
there are no well-defined criteria to discriminate proximal from distal
obstructions, and surgical candidacy depends mostly on the surgeon's experience.
The intraoperative classification of chronic thromboembolic pulmonary
hypertension describes 4 types of lesions, based on anatomy and location. We
describe our recent experience with the more distal (type 3) disease. METHODS:
More than 500 pulmonary endarterectomies were performed at Foundation I.R.C.C.S.
Policlinico San Matteo (Pavia, Italy). Because of recent changes in the patient
population, 331 endarterectomies performed from January 2008 to December 2013
were analyzed. Two groups of patients were identified according to the
intraoperative classification: proximal (type 1 and type 2 lesions, 221 patients)
and distal (type 3 lesions, 110 patients). RESULTS: The number of
endarterectomies for distal chronic thromboembolic pulmonary hypertension
increased significantly over time (currently ~37%). Deep venous thrombosis was
confirmed as a risk factor for proximal disease, whereas patients with distal
obstruction had a higher prevalence of indwelling intravascular devices. Overall
hospital mortality was 6.9%, with no difference in the 2 groups. Postoperative
survival was excellent. In all patients, surgery was followed by a significant
and sustained improvement in hemodynamic, echocardiographic, and functional
parameters, with no difference between proximal and distal cases. CONCLUSIONS:
Although distal chronic thromboembolic pulmonary hypertension represents the most
challenging situation, the postoperative outcomes of both proximal and distal
cases are excellent. The diagnosis of inoperable chronic thromboembolic pulmonary
hypertension should be achieved only in experienced centers, because many
patients who have been deemed inoperable might benefit from favorable surgical
outcomes.
PMID- 25129591
TI - Long-term outcomes after immediate aortic repair for acute type A aortic
dissection complicated by coma.
AB - OBJECTIVES: The management of acute type A aortic dissection complicated by coma
remains controversial. We previously reported an excellent rate of recovery of
consciousness provided aortic repair was performed within 5 hours of the onset of
symptoms. This study evaluates the early and long-term outcomes using this
approach. METHODS: Between August 2003 and July 2013, of the 241 patients with
acute type A aortic dissection brought to the Japanese Red Cross Kobe Hospital
and Hyogo Emergency Medical Center, 30 (12.4%) presented with coma; Glasgow Coma
Scale was less than 11 on arrival. Surgery was performed in 186 patients,
including 27 (14.5%) who were comatose. Twenty-four comatose patients underwent
successful aortic repair immediately (immediate group). Their mean age was 71.0
+/- 11.1 years, Glasgow Coma Scale was 6.5 +/- 2.4, and prevalence of carotid
dissection was 79%. For brain protection, deep hypothermia with antegrade
cerebral perfusion was used, and postoperative induced hypothermia was performed.
Neurologic evaluations were performed using the Glasgow Coma Scale, National
Institutes of Health Stroke Scale, and modified Rankin Scale. RESULTS: In the
immediate group, the time from the onset of symptoms to arrival in the operating
theater was 222 +/- 86 minutes. Hospital mortality was 12.5%. Full recovery of
consciousness was achieved in 79% of patients in up to 30 days. Postoperative
Glasgow Coma Scale and National Institutes of Health Stroke Scale improved
significantly when compared with the preoperative score (P < .05), and
postoperative activities of daily living independence (modified Rankin Scale <3)
was achieved in 50% of patients. The mean follow-up period was 56.5 months, and
the cumulative survival was 48.2% after 10 years. Cox proportional hazards
regression analysis indicated that immediate repair (hazard ratio, 4.3; P = .007)
was the only significant predictor of postoperative survival over a 5-year
period. CONCLUSIONS: The early and long-term outcomes as a result of immediate
aortic repair for acute type A aortic dissection complicated by coma were
satisfactory.
PMID- 25129593
TI - Management of mitral regurgitation in Marfan syndrome: Outcomes of valve repair
versus replacement and comparison with myxomatous mitral valve disease.
AB - OBJECTIVES: The study objective was to evaluate patients with Marfan syndrome and
mitral valve regurgitation undergoing valve repair or replacement and to compare
them with patients undergoing repair for myxomatous mitral valve disease.
METHODS: We reviewed the medical records of consecutive patients with Marfan
syndrome treated surgically between March 17, 1960, and September 12, 2011, for
mitral regurgitation and performed a subanalysis of those with repairs compared
with case-matched patients with myxomatous mitral valve disease who had repairs
(March 14, 1995, to July 5, 2013). RESULTS: Of 61 consecutive patients, 40
underwent mitral repair and 21 underwent mitral replacement (mean [standard
deviation] age, 40 [18] vs 31 [19] years; P = .09). Concomitant aortic surgery
was performed to a similar extent (repair, 45% [18/40] vs replacement, 43%
[9/21]; P = .87). Ten-year survival was significantly better in patients with
Marfan syndrome with mitral repair than in those with replacement (80% vs 41%; P
= .01). Mitral reintervention did not differ between mitral repair and
replacement (cumulative risk of reoperation, 27% vs 15%; P = .64). In the matched
cohort, 10-year survival after repair was similar for patients with Marfan
syndrome and myxomatous mitral disease (84% vs 78%; P = .63), as was cumulative
risk of reoperation (17% vs 12%; P = .61). CONCLUSIONS: Patients with Marfan
syndrome and mitral regurgitation have better survival with repair than with
replacement. Survival and risk of reoperation for patients with Marfan syndrome
were similar to those for patients with myxomatous mitral disease. These results
support the use of mitral valve repair in patients with Marfan syndrome and
moderate or more mitral regurgitation, including those having composite
replacement of the aortic root.
PMID- 25129595
TI - Topical vancomycin in combination with perioperative antibiotics and tight
glycemic control helps to eliminate sternal wound infections.
AB - OBJECTIVE: This study was undertaken to determine whether topical vancomycin
would further reduce the incidence of sternal infections in the presence of
perioperative antibiotics and tight glycemic control. METHODS: A total of 1075
consecutive patients undergoing cardiac surgery from December 2007 to August 2013
receiving topical vancomycin (2.5 g in 2 mL of normal saline) applied as a slurry
to the cut edges of the sternum were compared with 2190 patients from December
2003 to November 2007 who did not receive topical vancomycin. All patients
received perioperative antibiotics (cefazolin 2 g intravenously every 8 hours and
vancomycin 1 g intravenously every 12 hours) on induction of anesthetic and
continuing for 48 hours; and intravenous insulin infusions to maintain serum
blood glucose level between 120 and 180 mg/dL. RESULTS: Patients receiving
topical vancomycin had less superficial sternal infections (0% vs 1.6%; P <
.0001), deep sternal infections (0% vs 0.7%; P = .005), any type of sternal
infection (0% vs 2.2%; P < .0001) and significantly less sternal infections of
any type in patients with diabetes mellitus (0% vs 3.3%; P = .0004). CONCLUSIONS:
Topical vancomycin applied to the sternal edges, in conjunction with
perioperative antibiotics and tight glycemic control, helps to eliminate wound
infections in cardiac surgical patients.
PMID- 25129597
TI - Circulating tumor cells from a 4-dimensional lung cancer model are resistant to
cisplatin.
AB - OBJECTIVE: To determine the effect of cisplatin on circulatory tumor cells (CTC)
and tumor nodules in a four-dimensional (4D) lung cancer model. METHODS: CTCs
from the 4D model seeded with H1299, A549, or H460 and respective cells that were
grown under two-dimensional conditions in a Petri dish were treated with 50 MUM
cisplatin for 24 and 48 hours and cell viability was determined. The lung nodules
in the 4D model were then treated with different continuous or intermittent doses
of cisplatin and the nodule size, the number of CTCs, and the level of matrix
metalloproteinase (MMP) were determined. RESULTS: Cisplatin led to a significant
decrease in the viability of tumor cells grown under 2D conditions (P < .01) but
not in CTCs from the 4D model after both 24 hours and 48 hours. Cisplatin led to
regression of tumor nodules with both the continuous and intermittent treatments.
Moreover, there was a significantly higher number of CTCs per tumor area (P <
.05) and MMP-2 production per tumor area (P = .007) for all human lung cancer
cell lines grown in the 4D model when treated with cisplatin. CONCLUSIONS: The 4D
lung cancer model allows for the isolation of CTCs that are resistant to
cisplatin treatment. The model may allow us to better understand the biology of
cisplatin resistance.
PMID- 25129599
TI - Quantitative analysis of exhaled carbonyl compounds distinguishes benign from
malignant pulmonary disease.
AB - OBJECTIVES: The analysis of exhaled breath is a promising noninvasive tool for
the diagnosis of lung cancer, but its clinical relevance has yet to be
established. We report the analysis of exhaled volatile carbonyl compounds for
the identification of specific carbonyl cancer markers to differentiate benign
pulmonary disease from early-stage lung cancer and to compare its diagnostic
accuracy with positron emission tomography (PET) scans. METHODS: Aminooxy-coated
silicon microchips were used for the selective capture of exhaled carbonyls by an
oximation reaction. Breath samples were collected then directed through the
silicon chips by applying a vacuum. Carbonyl adducts were analyzed by Fourier
transform mass spectrometry. Eighty-eight control subjects, 107 patients with
lung cancer (64 stage 0, I, or II), 40 patients with benign pulmonary disease,
and 7 patients with a solitary pulmonary metastasis participated. Analysis of
cancer markers was performed blinded to the pathologic results. RESULTS: Four
carbonyls were defined as cancer markers with significantly higher concentrations
in patients with lung cancer. The number of increased cancer markers
distinguished benign disease from both early and stage III and IV lung cancer.
For early-stage disease, defining greater than 2 increased markers as diagnostic
of lung cancer resulted in 83% sensitivity and 74% specificity. PET scans for
this same cohort resulted in 90% sensitivity but only 39% specificity. Markers
normalized for 3 of the 4 markers after resection of the lung cancer.
CONCLUSIONS: Analysis of specific exhaled carbonyls can differentiate early lung
cancer from benign pulmonary disease. Breath analysis was more specific than PET
for a lung cancer diagnosis. Judicious use of these data may expedite the care of
patients with lung cancer.
PMID- 25129601
TI - Energy loss, a novel biomechanical parameter, correlates with aortic aneurysm
size and histopathologic findings.
AB - OBJECTIVE: Energy loss is a biomechanical parameter that represents the relative
amount of energy absorbed by the aorta during the cardiac cycle. We aimed to
correlate energy loss with ascending aortic aneurysm size and histopathologic
findings to elucidate the pathophysiology of aneurysm complications. METHODS:
Aneurysmal ascending aortic specimens were obtained during surgery. Control
specimens were obtained from autopsy and organ donors. Biaxial tensile tests were
performed on the 4 quadrants of the aortic ring. Energy loss was calculated using
the integral of the stress-strain curve during loading and unloading. It was
compared with the size and the traditional biomechanical parameter, stiffness
(apparent modulus of elasticity). Elastin, collagen, and mucopolysaccharide
content were quantified using Movat pentachrome staining of histology slides.
RESULTS: A total of 41 aortas were collected (34 aneurysmal, 7 control). The
aneurysms exhibited increased stiffness (P < .0001) and energy loss (P < .0001)
compared with the controls. Energy loss correlated significantly with aortic size
(P < .0001, r(2) = .60). A hinge point was noted at a diameter of 5.5 cm, after
which energy loss increased rapidly. The relationship between energy loss and
size became strongly linear once the size was indexed to the body surface area (P
< .0001, r(2) = .78). Energy loss correlated with the histopathologic findings,
especially the collagen/elastin ratio (P = .0002, r(2) = .49). High energy loss
distinguished patients with pathologic histologic findings from others with
similar diameters. CONCLUSIONS: As ascending aortas dilate, they exhibit greater
energy loss that rapidly increases after 5.5 cm. This mirrors the increase in
complications at this size. Energy loss correlates with imbalances in elastin and
collagen composition, suggesting a measurable link between the histopathologic
features and mechanical function.
PMID- 25129605
TI - Outcomes after implantation of partial-support left ventricular assist devices in
inotropic-dependent patients: Do we still need full-support assist devices?
AB - OBJECTIVES: Partial-support left ventricular assist devices (LVADs) represent a
novel strategy for heart failure treatment. The Synergy Pocket Micro-pump
(HeartWare Inc, Framingham, Mass), the smallest surgically implanted long-term
LVAD, provides partial flow up to 4.25 L/min and was primarily designed for "less
sick" patients with severe heart failure. This device is implanted minimally
invasively without sternotomy or cardiopulmonary bypass. Early implantation in
patients with Interagency Registry for Mechanically Assisted Circulatory Support
class 4 and higher was shown to be feasible and associated with significantly
improved hemodynamics and quality of life. The aim of this study was to present
our experience with implementation of long-term partial circulatory support as a
bridge to transplantation in patients with more advanced heart failure who were
dependent preoperatively on inotropic support or intra-aortic balloon pump.
METHODS: In this observational study, only inotropic or intra-aortic balloon pump
dependent patients with end-stage heart failure were included (n = 12). These
patients underwent Synergy device implantation between February 2012 and August
2013. RESULTS: The mean preoperative Interagency Registry for Mechanically
Assisted Circulatory Support class was 2.17 +/- 0.84 (class 1, 25%; class 2, 33%;
class 3, 42%). The mean age was 46 +/- 15 years, and 33% were female.
Preoperatively, 4 patients (33%) had at least 1 previous sternotomy, 3 patients
(25%) were supported with a balloon pump, 1 patient (8%) had a previous full
support LVAD, and 4 patients (33%) had cerebrovascular events in the past. After
device implantation, there were no right ventricular failures, device-related
infections, hemorrhagic strokes, arterial or venous thromboembolisms, or
worsenings of aortic and mitral regurgitation observed over the follow-up. The
mean follow up was 174 +/- 171 days (range, 5-764 days; cumulative, 3199 days).
One patient (8%) died, 3 patients (25%) successfully underwent transplantation, 1
device (8%) was explanted after myocardial recovery, and 5 patients (42%) are
still on ongoing support. Two patients (17%) were upgraded to a full-support LVAD
after 65 days of mean support. A total of 11 of 12 patients (92%) were discharged
from the hospital and are presently alive. Left ventricular end-diastolic
diameter was significantly reduced 3 months after device implantation.
CONCLUSIONS: Partial LVAD support may be clinically efficacious in inotropic and
intra-aortic balloon pump-dependent patients. On the basis of our experience and
evidence of previous research, such patients may benefit from minimally invasive
access, no need for sternotomy and cardiopulmonary bypass, a short implantation
time, an easy exchange if necessary, and a lower risk of subsequent heart
transplantation. Because the implantation is performed without sternotomy, device
upgrade is feasible with a comparatively low operative risk and good clinical
outcome. Our preliminary results show that partial-support devices may have the
potential to replace full-support LVADs in the near future.
PMID- 25129603
TI - Tissue-engineered, hydrogel-based endothelial progenitor cell therapy robustly
revascularizes ischemic myocardium and preserves ventricular function.
AB - OBJECTIVES: Cell-based angiogenic therapy for ischemic heart failure has had
limited clinical impact, likely related to low cell retention (<1%) and
dispersion. We developed a novel, tissue-engineered, hydrogel-based cell-delivery
strategy to overcome these limitations and provide prolonged regional retention
of myocardial endothelial progenitor cells at high cell dosage. METHODS:
Endothelial progenitor cells were isolated from Wistar rats and encapsulated in
fibrin gels. In vitro viability was quantified using a fluorescent live-dead
stain of transgenic enhanced green fluorescent protein(+) endothelial progenitor
cells. Endothelial progenitor cell-laden constructs were implanted onto ischemic
rat myocardium in a model of acute myocardial infarction (left anterior
descending ligation) for 4 weeks. Intramyocardial cell injection (2 * 10(6)
endothelial progenitor cells), empty fibrin, and isolated left anterior
descending ligation groups served as controls. Hemodynamics were quantified using
echocardiography, Doppler flow analysis, and intraventricular pressure-volume
analysis. Vasculogenesis and ventricular geometry were quantified. Endothelial
progenitor cell migration was analyzed by using endothelial progenitor cells from
transgenic enhanced green fluorescent protein(+) rodents. RESULTS: Endothelial
progenitor cells demonstrated an overall 88.7% viability for all matrix and cell
conditions investigated after 48 hours. Histologic assessment of 1-week implants
demonstrated significant migration of transgenic enhanced green fluorescent
protein(+) endothelial progenitor cells from the fibrin matrix to the infarcted
myocardium compared with intramyocardial cell injection (28 +/- 12.3 cells/high
power field vs 2.4 +/- 2.1 cells/high power field, P = .0001). We also observed a
marked increase in vasculogenesis at the implant site. Significant improvements
in ventricular hemodynamics and geometry were present after endothelial
progenitor cell-hydrogel therapy compared with control. CONCLUSIONS: We present a
tissue-engineered, hydrogel-based endothelial progenitor cell-mediated therapy to
enhance cell delivery, cell retention, vasculogenesis, and preservation of
myocardial structure and function.
PMID- 25129607
TI - Functional evaluation of human donation after cardiac death donor hearts using a
continuous isolated myocardial perfusion technique: Potential for expansion of
the cardiac donor population.
AB - OBJECTIVE: To investigate the resuscitation potential and contractile function in
adult human donation after cardiac death (DCD) hearts by ex vivo perfusion.
METHODS: With institutional review board approval and under the DCD protocol at
the University of Wisconsin (UW) Organ Procurement Organization, 5 brain dead
(BD) and 5 DCD donor hearts were evaluated. All BD hearts were declined for
clinical transplantation because of coronary artery disease, advanced age, or
social history. All hearts were preserved by flushing and cold storage with UW
solution. By using our ex vivo perfusion system, the left ventricular end
systolic pressure-volume relationship (LV-ESPVR) was assessed for 2 hours of
oxygenated blood reperfusion. RESULTS: All BD (n = 5) and 4 DCD hearts were
successfully resuscitated. One DCD heart was unable to be resuscitated due to
prolonged warm ischemic time (WIT; 174 minutes). Mean WIT for resuscitated DCD
hearts (from extubation to flushing with cold UW solution) was 34 +/- 3 minutes
(range, 26 to 40 minutes); mean cold ischemic time for BD donors was 211 +/- 31
minutes compared with 177 +/- 64 minutes for DCD donors. The calculated LV-ESPVRs
for BD hearts after 1 and 2 hours of reperfusion were 6.9 +/- 0.7 and 5.7 +/- 1.0
mm Hg/mL, respectively; LV-ESPVRs for DCD hearts after 1 and 2 hours of
reperfusion were 5.6 +/- 1.5 (P = .45) and 3.0 +/- 0.7 mm Hg/mL (P = .07),
respectively. CONCLUSIONS: We successfully resuscitated and measured ex vivo
cardiac function in human DCD and BD donor hearts. Resuscitation potential in DCD
hearts was achieved when the WIT was less than 40 minutes. Contractile
performance in DCD hearts tended to be lower compared with BD hearts. Further
investigation with longer reperfusion periods seems warranted.
PMID- 25129610
TI - Synergistic proteins for the enhanced enzymatic hydrolysis of cellulose by
cellulase.
AB - Reducing the enzyme loadings for enzymatic saccharification of lignocellulose is
required for economically feasible production of biofuels and biochemicals. One
strategy is addition of small amounts of synergistic proteins to cellulase
mixtures. Synergistic proteins increase the activity of cellulase without causing
significant hydrolysis of cellulose. Synergistic proteins exert their activity by
inducing structural modifications in cellulose. Recently, synergistic proteins
from various biological sources, including bacteria, fungi, and plants, were
identified based on genomic data, and their synergistic activities were
investigated. Currently, an up-to-date overview of several aspects of synergistic
proteins, such as their functions, action mechanisms and synergistic activity,
are important for future industrial application. In this review, we summarize the
current state of research on four synergistic proteins: carbohydrate-binding
modules, plant expansins, expansin-like proteins, and Auxiliary Activity family 9
(formerly GH61) proteins. This review provides critical information to aid in
promoting research on the development of efficient and industrially feasible
synergistic proteins.
PMID- 25129611
TI - Production of functional inclusion bodies in endotoxin-free Escherichia coli.
AB - Escherichia coli is the workhorse for gene cloning and production of soluble
recombinant proteins in both biotechnological and biomedical industries. The
bacterium is also a good producer of several classes of protein-based self
assembling materials such as inclusion bodies (IBs). Apart from being a
relatively pure source of protein for in vitro refolding, IBs are under
exploration as functional, protein-releasing materials in regenerative medicine
and protein replacement therapies. Endotoxin removal is a critical step for
downstream applications of therapeutic proteins. The same holds true for IBs as
they are often highly contaminated with cell-wall components of the host cells.
Here, we have investigated the production of IBs in a recently developed
endotoxin-free E. coli strain. The characterization of IBs revealed this mutant
as a very useful cell factory for the production of functional endotoxin-free IBs
that are suitable for the use at biological interfaces without inducing endotoxic
responses in human immune cells.
PMID- 25129612
TI - Bis (aspirinato) zinc (II) complex successfully inhibits carotid arterial
neointima formation after balloon-injury in rats.
AB - PURPOSE: Neointima formation following angioplasty is a serious consequence of
endothelial damage in arteries. Inflammatory mediators and lack of endothelial
regulatory mechanisms lead to migration and proliferation of smooth-muscle cells
and thus to restenosis. This study examines the effect of the novel bis
(aspirinato) zinc (II) complex on neointima formation in a rat model of carotid
balloon-injury. METHODS: Rats underwent balloon-injury of the right common
carotid artery, then received PEG400 vehicle (untreated-group), acetylsalicylic
acid (ASA-group), zinc-chloride (Zn-group) and bis (aspirinato) zinc (II) complex
(Zn(ASA) 2-group) orally for 18 consecutive days. From harvested carotid
arteries, histology, immunohistochemistry and mRNA expression analysis were
performed. RESULTS: Compared to the untreated-group, Zn (ASA) 2-treatment
significantly lowered stenosis ratio (54.0 +/- 5.8% to 25.5 +/- 3.9%) and reduced
neointima/media ratio (1.5 +/- 0.2 to 0.5 +/- 0.1). Significantly higher alpha
smooth muscle actin mRNA and protein expression were measured after Zn (ASA)2 and
Zn-treatment in comparison with the untreated and ASA-groups while the expression
of matrix-metalloproteinase-9 was significantly higher in these groups compared
to Zn (ASA)2. The presence of collagen in media was significantly decreased in
all treated groups. mRNA expressions of nuclear factor kappa-b, transforming
growth-factor-beta and proliferating cell nuclear antigen were significantly down
regulated, whereas a20 was up-regulated by Zn (ASA)2 treatment compared to the
untreated and ASA-groups. CONCLUSION: This study proves the effectivity of the
novel bis (aspirinato) zinc complex in reducing neointima formation and
restenosis after balloon-injury and supports the hypothesis that inhibition of
smooth-muscle transformation/proliferation plays a key role in the prevention of
restenosis.
PMID- 25129613
TI - Factors influencing eligibility for breast boost using noninvasive image-guided
breast brachytherapy.
AB - PURPOSE: Noninvasive image-guided breast brachytherapy (NIBB) allows for accurate
targeting of the tumor bed (TB) for breast boost by using breast immobilization
and image guidance. However, not all patients are candidates for this technique.
METHODS: Consecutive patients treated for breast cancer were evaluated. Patients
with very small breast size (cup <= A) for whom immobilization could not be
achieved were treated with electrons. All others underwent simulation for NIBB
boost. The rate of eligibility for NIBB, reasons for ineligibility, and related
patient and anatomic factors were analyzed. RESULTS: Of 52 patients evaluated, 6
patients were ineligible for NIBB because of small breast size. Of the remaining
patients who underwent simulation for NIBB boost, 33 patients (72%) were treated
with NIBB. Reasons for ineligibility were the absence of identifiable TB (n = 5),
inability to position patient/breast to adequately target the TB (n = 4),
posterior TB location (n = 3), and discomfort during compression (n = 1). The
likelihood of being eligible for NIBB boost was dependent on breast size: <=A
(0%), B (50%), C (71%), D-DD (77%), and >DD (80%) (p = 0.002). The presence of
surgical clips also predicted eligibility for NIBB: 79% clips vs. 45% without
clips (p = 0.05). A posterior TB location was not associated with ineligibility
(p = 0.2). CONCLUSIONS: NIBB boost is feasible in most patients. Patients with
larger breast size are more likely to be good candidates. Posterior TB location
can be challenging for NIBB, but most patients are still candidates. Surgical
clips are very helpful in defining the TB and greatly increase the likelihood of
eligibility for NIBB.
PMID- 25129615
TI - Set-back versus buried vertical mattress suturing: results of a randomized
blinded trial.
AB - BACKGROUND: The set-back suture, an absorbable dermal suturing technique,
purportedly improves wound eversion and cosmetic outcomes. OBJECTIVE: We sought
to conduct a split-wound, prospective, randomized study to compare the cosmetic
outcome and wound eversion achieved with the set-back suture and the buried
vertical mattress suture (BVMS). METHODS: A total of 46 surgical elliptical
wounds were randomized to subcuticular closure with the set-back suture on half
and the BVMS on the other. Maximum eversion height and width were measured
immediately postoperatively. At 3 months, 2 blinded observers evaluated each scar
using a 7-point Likert physician global scar assessment scale. Subjects and
observers also completed the validated Patient and Observer Scar Assessment
Scale, where a score of 6 represents normal-appearing skin and 60 represents
worst imaginable scar. RESULTS: In all, 42 subjects completed the study. The set
back suture provided statistically significant wound eversion. On the Likert
scale, observers rated the set-back suture side 1 point better than the BVMS
side. Both patient and observer total Patient and Observer Scar Assessment Scale
scores were significantly lower for the set-back suture side (subject mean 13.0
+/- 8.7 vs 16.2 +/- 12.0 [P = .039]; observer mean 24.5 +/- 10.4 vs 27.7 +/- 13.6
[P = .028], respectively). LIMITATIONS: Single institution experience and
relatively short follow-up are limitations. CONCLUSION: The set-back suture
provides superior wound eversion and better cosmetic outcomes than the BVMS.
PMID- 25129614
TI - Soluble amyloid beta levels are elevated in the white matter of Alzheimer's
patients, independent of cortical plaque severity.
AB - Alzheimer's disease (AD) is the most common neurodegenerative disease and the
leading cause of dementia. In addition to grey matter pathology, white matter
changes are now recognized as an important pathological feature in the emergence
of the disease. Despite growing recognition of the importance of white matter
abnormalities in the pathogenesis of AD, the causes of white matter degeneration
are still unknown. While multiple studies propose Wallerian-like degeneration as
the source of white matter change, others suggest that primary white matter
pathology may be due, at least in part, to other mechanisms, including local
effects of toxic Abeta peptides. In the current study, we investigated levels of
soluble amyloid-beta (Abeta) in white matter of AD patients (n=12) compared with
controls (n=10). Fresh frozen white matter samples were obtained from anterior
(Brodmann area 9) and posterior (Brodmann area 1, 2 and 3) areas of post-mortem
AD and control brains. ELISA was used to examine levels of soluble Abeta -42 and
Abeta -40. Total cortical neuritic plaque severity rating was derived from
individual ratings in the following areas of cortex: mid-frontal, superior
temporal, pre-central, inferior parietal, hippocampus (CA1), subiculum,
entorhinal cortex, transentorhinal cortex, inferior temporal, amygdala and basal
forebrain. Compared with controls, AD samples had higher white matter levels of
both soluble Abeta -42 and Abeta -40. While no regional white matter differences
were found in Abeta -40, Abeta -42 levels were higher in anterior regions than in
posterior regions across both groups. After statistically controlling for total
cortical neuritic plaque severity, differences in both soluble Abeta -42 and
Abeta -40 between the groups remained, suggesting that white matter Abeta
peptides accumulate independent of overall grey matter fibrillar amyloid
pathology and are not simply a reflection of overall amyloid burden. These
results shed light on one potential mechanism through which white matter
degeneration may occur in AD. Given that white matter degeneration may be an
early marker of disease, preceding grey matter atrophy, understanding the
mechanisms and risk factors that may lead to white matter loss could help to
identify those at high risk and to intervene earlier in the pathogenic process.
PMID- 25129609
TI - 2014 AATS guidelines for the prevention and management of perioperative atrial
fibrillation and flutter for thoracic surgical procedures.
PMID- 25129616
TI - Substrate derived peptidic alpha-ketoamides as inhibitors of the malarial
protease PfSUB1.
AB - Peptidic alpha-ketoamides have been developed as inhibitors of the malarial
protease PfSUB1. The design of inhibitors was based on the best known endogenous
PfSUB1 substrate sequence, leading to compounds with low micromolar to
submicromolar inhibitory activity. SAR studies were performed indicating the
requirement of an aspartate mimicking the P1' substituent and optimal P1-P4
length of the non-prime part. The importance of each of the P1-P4 amino acid side
chains was investigated, revealing crucial interactions and size limitations.
PMID- 25129617
TI - New insights into the genetics of 5-oxoprolinase deficiency and further evidence
that it is a benign biochemical condition.
AB - Inherited 5-oxoprolinase (OPLAH) deficiency is a rare inborn condition
characterised by 5-oxoprolinuria. To date, three OPLAH mutations have been
described: p.H870Pfs in a homozygous state, which results in a truncated protein,
was reported in two siblings, and two heterozygous missense changes, p.S323R and
p.V1089I, were independently identified in two unrelated patients. We describe
the clinical context of a young girl who manifested 5-oxoprolinuria together with
dusky episodes and who is compound heterozygote for two novel OPLAH variations:
p.G860R and p.D1241V. To gain insight into the aetiology of the 5-oxoprolinase
deficiency, we investigated the pathogenicity of all the reported missense
mutations in the OPLAH gene. A yeast in vivo growth assay revealed that only
p.S323R, p.G860R and p.D1241V affected the activity of the enzyme. CONCLUSION:
Taken together, this report further suggests that hereditary 5-oxoprolinase
deficiency is a benign biochemical condition caused by mutations in the OPLAH
gene, which are transmitted in an autosomal recessive manner, but 5-oxoprolinuria
may be a chance association in other disorders.
PMID- 25129618
TI - Direct observation of ferroelectric field effect and vacancy-controlled screening
at the BiFeO3/LaxSr1-xMnO3 interface.
AB - The development of interface-based magnetoelectric devices necessitates an
understanding of polarization-mediated electronic phenomena and atomistic
polarization screening mechanisms. In this work, the LSMO/BFO interface is
studied on a single unit-cell level through a combination of direct order
parameter mapping by scanning transmission electron microscopy and electron
energy-loss spectroscopy. We demonstrate an unexpected ~5% lattice expansion for
regions with negative polarization charge, with a concurrent anomalous decrease
of the Mn valence and change in oxygen K-edge intensity. We interpret this
behaviour as direct evidence for screening by oxygen vacancies. The vacancies are
predominantly accumulated at the second atomic layer of BFO, reflecting the
difference of ionic conductivity between the components. This vacancy exclusion
from the interface leads to the formation of a tail-to-tail domain wall. At the
same time, purely electronic screening is realized for positive polarization
charge, with insignificant changes in lattice and electronic properties. These
results underline the non-trivial role of electrochemical phenomena in
determining the functional properties of oxide interfaces. Furthermore, these
behaviours suggest that vacancy dynamics and exclusion play major roles in
determining interface functionality in oxide multilayers, providing clear
implications for novel functionalities in potential electronic devices.
PMID- 25129620
TI - Nanoelectrical analysis of single molecules and atomic-scale materials at the
solid/liquid interface.
AB - Evaluating the built-in functionality of nanomaterials under practical conditions
is central for their proposed integration as active components in next-generation
electronics. Low-dimensional materials from single atoms to molecules have been
consistently resolved and manipulated under ultrahigh vacuum at low temperatures.
At room temperature, atomic-scale imaging has also been performed by probing
materials at the solid/liquid interface. We exploit this electrical interface to
develop a robust electronic decoupling platform that provides precise information
on molecular energy levels recorded using in situ scanning tunnelling
microscopy/spectroscopy with high spatial and energy resolution in a high-density
liquid environment. Our experimental findings, supported by ab initio electronic
structure calculations and atomic-scale molecular dynamics simulations, reveal
direct mapping of single-molecule structure and resonance states at the
solid/liquid interface. We further extend this approach to resolve the electronic
structure of graphene monolayers at atomic length scales under standard room
temperature operating conditions.
PMID- 25129619
TI - Collective and individual migration following the epithelial-mesenchymal
transition.
AB - During cancer progression, malignant cells in the tumour invade surrounding
tissues. This transformation of adherent cells to a motile phenotype has been
associated with the epithelial-mesenchymal transition (EMT). Here, we show that
EMT-activated cells migrate through micropillar arrays as a collectively
advancing front that scatters individual cells. Individual cells with few
neighbours dispersed with fast, straight trajectories, whereas cells that
encountered many neighbours migrated collectively with epithelial biomarkers. We
modelled these emergent dynamics using a physical analogy to phase transitions
during binary-mixture solidification, and validated it using drug perturbations,
which revealed that individually migrating cells exhibit diminished
chemosensitivity. Our measurements also indicate a degree of phenotypic
plasticity as cells interconvert between individual and collective migration. The
study of multicellular behaviours with single-cell resolution should enable
further quantitative insights into heterogeneous tumour invasion.
PMID- 25129621
TI - Absorbed doses in tissue-equivalent spheres above radioactive sources in soil.
AB - Doses due to external exposure of terrestrial biota are assessed using
differential air kerma from radioactive sources in soil and energy-dependent
'absorbed dose-per-air kerma' conversion factors computed for spherical tissue
equivalent bodies. The presented approach allows computing average whole body
absorbed dose for terrestrial organisms with body masses from 1 mg to 1,000 kg
located at heights from 10 cm to 500 m above ground. Radioactive sources in soil
emitting photons with energies from 10 keV to 10 MeV have been considered.
Interpolation of the computed quantities over source energy, body mass, and
height above ground results in plausible estimates of whole body average absorbed
doses for non-human terrestrial biota from gamma-radiation emitted by any
radionuclides in contaminated terrain.
PMID- 25129622
TI - 13Calpha decoupling during direct observation of carbonyl resonances in solution
NMR of isotopically enriched proteins.
AB - Direct detection of (13)C can be advantageous when studying uniformly enriched
proteins, in particular for paramagnetic proteins or when hydrogen exchange with
solvent is fast. A scheme recently introduced for long-observation-window band
selective homonuclear decoupling in solid state NMR, LOW-BASHD (Struppe et al. in
J Magn Reson 236:89-94, 2013) is shown to be effective for (13)C(alpha)
decoupling during direct (13)C' observation in solution NMR experiments too. For
this purpose, adjustment of the decoupling pulse parameters and delays is
demonstrated to be important for increasing spectral resolution, to reduce three
spin effects, and to decrease the intensity of decoupling side-bands. LOW-BASHD
then yields (13)C' line widths comparable to those obtained with the popular IPAP
method, while enhancing sensitivity by ca 35 %. As a practical application of LOW
BASHD decoupling, requiring quantitative intensity measurement over a wide
dynamic range, the impact of lipid binding on the (13)C'-detected NCO spectrum of
the intrinsically disordered protein alpha-synuclein is compared with that on the
(1)H-detected (1)H-(15)N HSQC spectrum. Results confirm that synuclein's "dark
state" behavior is not caused by paramagnetic relaxation or rapid hydrogen
exchange.
PMID- 25129623
TI - Effective strategy to assign 1H- 15N heteronuclear correlation NMR signals from
lysine side-chain NH33+ groups of proteins at low temperature.
AB - Recent studies have shown that lysine side-chain NH3(+) groups are excellent
probes for NMR investigations of dynamics involving hydrogen bonds and ion pairs
relevant to protein function. However, due to rapid hydrogen exchange,
observation of (1)H-(15)N NMR cross peaks from lysine NH3(+) groups often
requires use of a relatively low temperature, which renders difficulty in
resonance assignment. Here we present an effective strategy to assign (1)H and
(15)N resonances of NH3(+) groups at low temperatures. This strategy involves two
new (1)H/(13)C/(15)N triple-resonance experiments for lysine side chains.
Application to a protein-DNA complex is demonstrated.
PMID- 25129624
TI - Synthesis, biological and comparative DFT studies on Ni(II) complexes of NO and
NOS donor ligands.
AB - Three new NOS donor ligands have been prepared by addition ethanolic suspension
of 2-hydrazino-2-oxo-N-phenyl-acetamide to phenyl isocyanate (H2PAPS), phenyl
isothiocyanate (H2PAPT) and benzoyl isothiocyanate (H2PABT). The Ni(II) complexes
prepared from the chloride salt and characterized by conventional techniques. The
isolated complexes were assigned the formulaes, [Ni2(PAPS)(H2O)2](H2O)2,
[Ni(H2PAPT)Cl2(H2O)](H2O)2 and [(Ni)2(HPABT)2Cl2(H2O)2], respectively. The IR
spectra of complexes shows that H2PAPS behaves as a binegative pentadentate via
both CO of hydrazide moiety in keto and enol form, enolized CO of cyanate moiety
and the CN (azomethine) groups of enolization. H2PAPT behaves as neutral
tridentate via both CO of hydrazide moiety and CN (azomethine) group due to SH
formation and finally H2PABT behaves as mononegative tetradentate via CO and
enolized CO of hydrazide moiety, CO of benzoyl moiety and C=S groups. The
experimental IR spectra of ligands are compared with those obtained theoretically
from DFT calculations. Also, the bond lengths, bond angles, HOMO (Highest
Occupied Molecular Orbitals), LUMO (Lowest Unoccupied Molecular Orbital) and
dipole moments have been calculated. The calculated HOMO-LUMO energy gap reveals
that charge transfer occurs within the molecule. The theoretical values of
binding energies indicate the higher stability of complexes than of ligands.
Also, the kinetic and thermodynamic parameters for the different thermal
degradation steps of the complexes were determined by Coats-Redfern and Horowitz
Metzger methods. The antibacterial activities were also tested against B.
Subtilis and E. coli bacteria. The free ligands showed a higher antibacterial
effect than their Ni(II) complexes. The antitumor activities of the Ligands and
their Ni(II) complexes have been evaluated against liver (HePG2) and breast (MCF
7) cancer cells. All ligands were found to display cytotoxicity that are better
than that of Fluorouracil (5-FU), while Ni(II) complexes show low activity.
PMID- 25129625
TI - On the spectroscopic analyses of 3-(4-Hydroxy-1-methyl-2-oxo-1,2-dihydro-quinolin
3-yl)-2-nitro-3-oxo-propionic acid (HMQNP).
AB - In the present work, a combined experimental and theoretical study on molecular
structure and vibrational frequencies of HMQNP were reported. The FT-IR spectrum
of HMQNP is recorded in the solid phase. The equilibrium geometries, harmonic
vibrational frequencies, thermo-chemical parameters, total dipole moment, nuclear
repulsion energy and HOMO-LUMO energies are calculated by DFT/B3LYP utilizing 6
311G(d,p) basis set. Results showed that HMQNP possesses a high dipole moment
value of 9.3 Debye. HMQNP spin is doublet state which enhances frontier molecular
orbitals to split into alpha (spin ?) and beta (spin ?) molecular orbitals with
two different energy gaps 4.2 and 2.7 eV, respectively. HMQNP is highly
recommended to be a more promising structure for many applications in
optoelectronic devices such as solar cells.
PMID- 25129626
TI - Synthesis, characterization and antimicrobial activities of mixed ligand
transition metal complexes with isatin monohydrazone Schiff base ligands and
heterocyclic nitrogen base.
AB - Mixed ligand complexes of Co(II), Ni(II), Cu(II) and Zn(II) with various
uninegative tridentate ligands derived from isatin monohydrazone with 2
hydroxynapthaldehyde/substituted salicylaldehyde and heterocyclic nitrogen base 8
hydroxyquinoline have been synthesized and characterized by elemental analysis,
conductometric studies, magnetic susceptibility and spectroscopic techniques (IR,
UV-VIS, NMR, mass and ESR). On the basis of these characterizations, it was
revealed that Schiff base ligands existed as monobasic tridentate ONO bonded to
metal ion through oxygen of carbonyl group, azomethine nitrogen and deprotonated
hydroxyl oxygen and heterocyclic nitrogen base 8-hydroxyquinoline existed as
monobasic bidentate ON bonded through oxygen of hydroxyl group and nitrogen of
quinoline ring with octahedral or distorted octahedral geometry around metal ion.
All the compounds have been tested in vitro against various pathogenic Gram
positive bacteria, Gram negative bacteria and fungi using different
concentrations (25, 50, 100, 200 MUg/mL) of ligands and their complexes.
Comparative study of antimicrobial activity of ligands, and their mixed complexes
indicated that complexes exhibit enhanced activity as compared to free ligands
and copper(II) Cu(LIV)(Q)?H2O complex was found to be most potent antimicrobial
agent.
PMID- 25129627
TI - Monteggia type IV fracture in a child with radial head dislocation irreducible by
closed means: a case report.
AB - BACKGROUND: Fractures of the proximal third of the ulna and radius with
associated anterior radial head dislocation are uncommon in children. Early
recognition and appropriate management are essential to prevent long-term
consequences of loss of forearm rotation, cubitus valgus, elbow instability and
chronic pain. CASE PRESENTATION: We present the case of a 3-year-old Caucasian
boy who attended the emergency department following an un-witnessed fall,
resulting in right elbow and forearm pain, swelling and deformity. Clinical and
radiological examination revealed a Monteggia type IV fracture-dislocation.The
patient was treated with closed manipulation and percutaneous fixation of both
bone forearm fractures with intra-medullary wires. After failed attempts at
closed reduction, open reduction of the radial head was required.The block to
reduction was due to a buttonholing of the radial head through the anterior joint
capsule, with interposition of the capsule in the radiocapitellar joint.
Subsequently, alignment was maintained with fracture healing. Follow-up at five
months showed a full range of elbow movement with no adverse symptoms.
CONCLUSION: Monteggia lesions of the paediatric elbow, albeit uncommon, should be
considered in all forearm fractures. Accurate reduction of the radiocapitellar
joint is crucial to prevent significant long-term consequences and failed closed
reduction requires open reduction. Here we have described the management of a
rare type IV lesion in which there was buttonholing of the radial head through
the anterior capsule, causing the radiocapitellar dislocation to be irreducible
(even after fixation of the radial and ulnar fractures).
PMID- 25129628
TI - Snowman sign: a possible predictor of catastrophic abnormal placentation.
PMID- 25129629
TI - Autonomy as self-sovereignty.
AB - The concept of autonomy as self-sovereignty is developed in this essay through an
examination of the thought of American transcendentalist philosophers Emerson and
Thoreau. It is conceived as the quality of living in accordance with one's inner
nature or genius. This conception is grounded in a transcendentalist moral
anthropology that values independence, self-reliance, spirituality, and the
capacity to find beauty in the world. Though still exerting considerable popular
and academic influence, both the concept of autonomy as self-sovereignty and the
underlying anthropology diverge in important ways from counterparts that are
prominent in contemporary bioethics. Autonomy as self-sovereignty calls into
question the manifold ways that patients (and citizens) are brought to heel by
institutional (and political) values they do not themselves affirm. It also
emphasizes the inevitable deep plurality of moral visions of health and
appropriate healthcare, rejecting tendencies (strong in mainstream bioethics) to
regard "health" as a univocal concept or healthcare as a basic need, to attempt
to conform "reasonable" clinical decision-making to a single model, and to
appoint government as a guarantor of access to healthcare or a regulator of
healthcare standards. Autonomy as self-sovereignty, like its competitors, can
justify itself only in question-begging terms. Still, bioethics might do well to
recognize it within the mix of moral visions.
PMID- 25129630
TI - Portions and sorts in Icelandic: an ERP study.
AB - An ERP study investigated the processing of mass nouns used to convey 'portions'
vs. 'sorts' interpretations in Icelandic. The sorts interpretation requires
semantic Coercion to a count noun; the portions interpretation entails extra
syntactic processing. Compared to a Neutral condition, Coercion escaped the
expected penalty (N400), but the Extra Syntax condition incurred the anticipated
costs (anterior negativity followed by P600). Furthermore, we examined the
effects of having to revise an initial commitment to head-noun status. When
another noun follows the mass noun (creating a compound), the second noun becomes
the head-noun. We hypothesized, for Icelandic, there would be no effect for Extra
Syntax because the compound should have been built before the second noun was
encountered; by contrast, for the Coercion and Neutral conditions, processing
costs would be incurred to detect and reconfigure the second noun as the head.
These predictions were largely borne out (early and sustained anterior
negativities).
PMID- 25129631
TI - Inflectional morphology in primary progressive aphasia: an elicited production
study.
AB - Inflectional morphology lies at the intersection of phonology, syntax and the
lexicon, three language domains that are differentially impacted in the three
main variants of primary progressive aphasia (PPA). To characterize spared and
impaired aspects of inflectional morphology in PPA, we elicited inflectional
morphemes in 48 individuals with PPA and 13 healthy age-matched controls. We
varied the factors of regularity, frequency, word class, and lexicality, and used
voxel-based morphometry to identify brain regions where atrophy was predictive of
deficits on particular conditions. All three PPA variants showed deficits in
inflectional morphology, with the specific nature of the deficits dependent on
the anatomical and linguistic features of each variant. Deficits in inflecting
low-frequency irregular words were associated with semantic PPA, with
lexical/semantic deficits, and with left temporal atrophy. Deficits in inflecting
pseudowords were associated with non-fluent/agrammatic and logopenic variants,
with phonological deficits, and with left frontal and parietal atrophy.
PMID- 25129632
TI - Role of chloride ions in the promotion of auxin-induced growth of maize
coleoptile segments.
AB - BACKGROUND AND AIMS: The mechanism of auxin action on ion transport in growing
cells has not been determined in detail. In particular, little is known about the
role of chloride in the auxin-induced growth of coleoptile cells. Moreover, the
data that do exist in the literature are controversial. This study describes
experiments that were carried out with maize (Zea mays) coleoptile segments, this
being a classical model system for studies of plant cell elongation growth.
METHODS: Growth kinetics or growth and pH changes were recorded in maize
coleoptiles using two independent measuring systems. The growth rate of the
segments was measured simultaneously with medium pH changes. Membrane potential
changes in parenchymal cells of the segments were also determined for chosen
variants. The question of whether anion transport is involved in auxin-induced
growth of maize coleoptile segments was primarily studied using anion channel
blockers [anthracene-9-carboxylic acid (A-9-C) and 4,4'-diisothiocyanatostilbene
2,2'-disulphonic acid (DIDS)]. In addition, experiments in which KCl was replaced
by KNO3 were also performed. KEY RESULTS: Both anion channel blockers, added at
0.1 mm, diminished indole-3-acetic acid (IAA)-induced elongation growth by ~30 %.
Medium pH changes measured simultaneously with growth indicated that while DIDS
stopped IAA-induced proton extrusion, A-9-C diminished it by only 50 %. Addition
of A-9-C to medium containing 1 mm KCl did not affect the characteristic kinetics
of IAA-induced membrane potential changes, while in the presence of 10 mm KCl the
channel blocker stopped IAA-induced membrane hyperpolarization. Replacement of
KCl with KNO3 significantly decreased IAA-induced growth and inhibited proton
extrusion. In contrast to the KCl concentration, the concentration of KNO3 did
not affect the growth-stimulatory effect of IAA. For comparison, the effects of
the cation channel blocker tetraethylammonium chloride (TEA-Cl) on IAA-induced
growth and proton extrusion were also determined. TEA-Cl, added 1 h before IAA,
caused reduction of growth by 49.9 % and inhibition of proton extrusion.
CONCLUSIONS: These results suggest that Cl(-) plays a role in the IAA-induced
growth of maize coleoptile segments. A possible mechanism for Cl(-) uptake during
IAA-induced growth is proposed in which uptake of K(+) and Cl(-) ions in concert
with IAA-induced plasma membrane H(+)-ATPase activity changes the membrane
potential to a value needed for turgor adjustment during the growth of maize
coleoptile cells.
PMID- 25129633
TI - Developmental changes in guard cell wall structure and pectin composition in the
moss Funaria: implications for function and evolution of stomata.
AB - BACKGROUND AND AIMS: In seed plants, the ability of guard cell walls to move is
imparted by pectins. Arabinan rhamnogalacturonan I (RG1) pectins confer
flexibility while unesterified homogalacturonan (HG) pectins impart rigidity.
Recognized as the first extant plants with stomata, mosses are key to
understanding guard cell function and evolution. Moss stomata open and close for
only a short period during capsule expansion. This study examines the
ultrastructure and pectin composition of guard cell walls during development in
Funaria hygrometrica and relates these features to the limited movement of
stomata. METHODS: Developing stomata were examined and immunogold-labelled in
transmission electron microscopy using monoclonal antibodies to five pectin
epitopes: LM19 (unesterified HG), LM20 (esterified HG), LM5 (galactan RG1), LM6
(arabinan RG1) and LM13 (linear arabinan RG1). Labels for pectin type were
quantitated and compared across walls and stages on replicated, independent
samples. KEY RESULTS: Walls were four times thinner before pore formation than in
mature stomata. When stomata opened and closed, guard cell walls were thin and
pectinaceous before the striated internal and thickest layer was deposited.
Unesterified HG localized strongly in early layers but weakly in the thick
internal layer. Labelling was weak for esterified HG, absent for galactan RG1 and
strong for arabinan RG1. Linear arabinan RG1 is the only pectin that exclusively
labelled guard cell walls. Pectin content decreased but the proportion of HG to
arabinans changed only slightly. CONCLUSIONS: This is the first study to
demonstrate changes in pectin composition during stomatal development in any
plant. Movement of Funaria stomata coincides with capsule expansion before
layering of guard cell walls is complete. Changes in wall architecture coupled
with a decrease in total pectin may be responsible for the inability of mature
stomata to move. Specialization of guard cells in mosses involves the addition of
linear arabinans.
PMID- 25129635
TI - Trends in analyzing emerging drugs of abuse--from seized samples to body samples.
AB - This article summarizes the current status of and new trends of analytical
approaches in the field of forensic/clinical toxicology for analyzing emerging
drugs of abuse. Instruments and devices used for compound identification will be
presented as well as types of biosample used to check for drug intake. Finally, a
new and promising strategy will be presented, which allows to monitor the
consumption of emerging drugs of abuse without using real body samples.
PMID- 25129634
TI - Quantification of cocaine and metabolites in exhaled breath by liquid
chromatography-high-resolution mass spectrometry following controlled
administration of intravenous cocaine.
AB - Breath has been investigated as an alternative matrix for detecting recent
cocaine intake; however, there are no controlled cocaine administration studies
that investigated the drug's disposition into breath. Breath was collected from
10 healthy adult cocaine users by asking them to breathe into a SensAbues device
for 3 min before and up to 22 h following 25 mg intravenous (IV) cocaine dosing
on days 1, 5, and 10, and assayed with a validated liquid chromatography-high
resolution mass spectrometry (LC-HRMS) method to quantify breath cocaine,
benzoylecgonine (BE), ecgonine methyl ester (EME), and norcocaine. The assay was
linear from 25 to 1,000 pg/filter, extraction efficiencies were 83.6-126%, intra-
and inter-assay imprecision was <10.6%, and bias was between -8.5 and 16.8%. No
endogenous or exogenous interferences were observed for more than 75 tested.
Analytes were generally stable under short-term storage conditions. Ion
suppression was less than 46%. Of breath specimens collected after controlled
cocaine administration, 2.6% were positive for cocaine (26.1-66 pg/filter, 1-9.5
h), 0.72% BE (83.3-151 pg/filter, 6.5-12.5 h), and 0.72% EME (50-69.1 pg/filter,
6.5-12.5 h); norcocaine was not detected. Methanolic extraction of the devices
themselves, after filters were removed, yielded 19.2% positive cocaine tests
(25.2-36.4 pg/device, 10 min-22 h) and 4.3% positive BE tests (26.4-93.7
pg/device, 10 min-22 h), explaining differences between the two extraction
techniques. These results suggest that the device reflects the drug in oral fluid
as well as lung microparticles, while the filter reflects only drug-laden
microparticles. A sensitive and specific method for cocaine, BE, EME, and
norcocaine quantification in breath was developed and validated. Cocaine in
breath identifies recent cocaine ingestion, but its absence does not preclude
recent use.
PMID- 25129636
TI - Reduced oocyte and embryo quality in response to elevated non-esterified fatty
acid concentrations: a possible pathway to subfertility?
AB - Reproductive performance is increasingly considered as a 'barometer' of general
well-being of the mother. A normal maternal 'metabolic health' status is
essential to safeguard successful ovulation, conception and further embryo
development. When alterations in serum metabolites are reflected in the oocyte
and embryonic micro-environment, these metabolic changes can affect follicle
health, oocyte development and even subsequent embryo physiology. The search
continues for signals that may be critically affecting the early developmental
stages in life. Years of expertise in animal in vitro embryo culture models
contribute to the awareness on the influence of elevated non-esterified fatty
acid (NEFA) concentrations on follicle cells, oocyte and embryo quality. High
NEFA concentrations in the blood are known to alter the follicular micro
environment. The latter alterations in NEFA concentrations have been associated
with a disappointing fertility outcome through disabled ovarian cell function and
reduced oocyte's developmental competence. Even more, elevated NEFA
concentrations during bovine oocyte maturation influence the subsequent embryo
characteristics. This review provides a cross-species overview on the
consequences of elevated NEFA concentrations, originating from maternal lipolytic
conditions, on female fertility, with particular focus on the early stages in
life. Thereby, we will describe to what extent elevated serum NEFA concentrations
are a potential threat around the period of conception.
PMID- 25129637
TI - Protein supplementation during a short-interval prostaglandin-based protocol for
timed AI in sheep.
AB - The aim of this experiment was to improve the reproductive performance of a short
interval prostaglandin (PG)-based protocol for timed artificial insemination in
sheep, using a short-term nutritional treatment. During the breeding season
(March-April), 132 multiparous and 61 nulliparous Corriedale ewes grazing natural
pastures (600 kg DM/ha, 8.5% CP), were allocated to two groups: 1, Control group
(n=100) two injections of D-Cloprostenol (75 MUg per dose, 7d apart:
Synchrovine((r)) protocol); and 2, Supplemented group (n=93) ewes in which stage
of the oestrous cycle was synchronised with Synchrovine((r)) protocol plus focus
feeding of a protein supplement (33.8% CP) between PG doses (Day -7 to -2).
Cervical AI was performed at fixed time (Day 0), 46 +/- 1.0 h after the second PG
injection using 150 million sperm per ewe. Ovulation rate (Day 10), pregnancy
rate, prolificacy and fecundity at Day 69 were evaluated by ultrasonography.
Ovulation rate at Day 10 (1.20 +/- 0.05 vs. 1.22 +/- 0.05), pregnancy (46 +/-
0.05 vs. 56 +/- 0.05), prolificacy (1.09 +/- 0.04 vs. 1.06 +/- 0.05), and
fecundity (0.49 +/- 0.06 vs. 0.59 +/- 0.06) at Day 69, were similar between
groups (P>0.05; Control and Supplemented group respectively). It is concluded
that focus feeding for 6d with protein supplementation during a short-interval PG
based protocol (Synchrovine((r))) did not improve the reproductive outcome
associated with this protocol.
PMID- 25129638
TI - Starting Ovsynch protocol on day 6 of first postpartum estrous cycle increased
fertility in dairy cows by affecting ovarian response during heat stress.
AB - The objective was to compare fertility in cows using an Ovsynch protocol starting
on day 6 of first postpartum estrous cycle with an Ovsynch protocol initiated at
random stages of the estrous cycle during heat stress (temperature-humidity index
(THI)=77-83). Cows (n=459) at the beginning of the lactation period were randomly
assigned to time-of-ovulation synchronization treatments: (1) control, Ovsynch
(first GnRH treatment, PGF2alpha treatment 7 days later, second GnRH treatment 56
h later, and TAI 16 h later), initiated at random stages of the estrous cycle (40
+/- 2 days postpartum, n=224) and (2) Ovsynch initiated on day 6 of first
postpartum estrous cycle (estrus=day 0) based on detection of the first estrus
after day 30 postpartum (O6, 35 +/- 2 postpartum, n=235). Statistical analyses
were conducted using SAS. The percentage of cows responding to the initial GnRH
injection using the Ovsynch protocol was greater with the O6 treatment compared
to the control treatment (60.4% compared with 52.6%). The percentage of cows
having a corpus luteum (CL) on the day of the PGF2alpha injection was not
different among treatments (control=87.0% and O6=90.2%, respectively). Also more
cows in the O6 treatment group responded to the second GnRH injection of the
Ovsynch protocol compared with control treatments (82.5% compared with 75.8%).
Treatment affected the percentage of cows diagnosed pregnant at 32 +/- 0.7 days
and 60 +/- 3 days after the resynchronized timing of AI but pregnancy losses
(5.3% compared with 6.8%) did not differ between treatment groups. It is
concluded that initiating the Ovsynch protocol 6 days after estrus during the
first 40 days postpartum resulted in a greater pregnancy rate at the synchronized
estrus and increased fertility compared with control cows during heat stress.
PMID- 25129639
TI - Impact of persistent smoking on long-term outcomes in patients with nonvalvular
atrial fibrillation.
AB - BACKGROUND: Although smoking is a risk factor for cardiovascular diseases, little
is known about the impact of smoking on long-term outcomes in patients with
atrial fibrillation (AF). METHODS: In 426 consecutive patients with nonvalvular
AF (mean age, 66 years; 307 men; mean follow-up, 5.8+/-3.2 years), clinical
variables including smoking status, CHADS2, and CHA2DS2-VASc score, incidences of
cardiovascular events (stroke, myocardial infarction, or admission for heart
failure), bleeding, and mortality were determined. RESULTS: Incidences of
intracranial bleeding (0.7% vs 0.1%/year, p<0.01), all-cause mortality (4.9% vs
2.6%/year, p<0.01), and death from stroke (0.8% vs 0.2%/year, p<0.05) were higher
in patients with history of smoking than in those without it. Incidence of
intracranial bleeding was significantly higher in persistent smokers than in non
persistent smokers (1.2% vs 0.2%/year, p<0.01). History of smoking predicted all
cause mortality [hazard ratio (HR), 2.7; 95% confidence interval (CI), 1.7-4.5;
p<0.01] and death from stroke (HR 4.7; 95% CI 1.0-22.3; p<0.05) independent of
age, antithrombotic treatment, CHADS2, and CHA2DS2-VASc score. Persistent smoking
predicted intracranial bleeding (HR 4.4; 95% CI 1.1-17.6; p<0.05) independent of
age and antithrombotic treatment. CONCLUSIONS: Smoking status, independent of
age, antithrombotic treatment, and clinical risk factors, predicted long-term
adverse outcomes including bleeding events in patients with nonvalvular AF. There
might be an obvious impact of persistent smoking on intracranial bleeding.
PMID- 25129640
TI - Multi-pore carbon phase plate for phase-contrast transmission electron
microscopy.
AB - A new fabrication method of carbon based phase plates for phase-contrast
transmission electron microscopy is presented. This method utilizes colloidal
masks to produce pores as well as disks on thin carbon membranes for phase
modulation. Since no serial process is involved, carbon phase plate membranes
containing hundreds of pores can be mass-produced on a large scale, which allows
"disposal" of contaminated or degraded phase modulating objects after use. Due to
the spherical shape of the mask colloid particles, the produced pores are
perfectly circular. The pore size and distribution can be easily tuned by the
mask colloid size and deposition condition. By using the stencil method, disk
type phase plates can also be fabricated on a pore type phase plate. Both pore
and disk type phase plates were tested by measuring amorphous samples and
confirmed to convert the sinus phase contrast transfer function to the cosine
shape.
PMID- 25129641
TI - Variability of Bacillus thuringiensis strains by ERIC-PCR and biofilm formation.
AB - Bacillus thuringiensis (Bt) is a soil-dwelling bacterium of great interest for
agronomical research because of its use as biological pesticide. There are some
limitations regarding the subspecies classification. Phenotyping and genotyping
studies are important to ascertain its variability. The diversity of 40
environmental strains, isolated from different regions in Mexico, was analyzed by
ERIC-PCR and the ability of biofilm formation. Thirty-nine different
fingerprinting patterns revealed enough data to discriminate among the 40
strains. A total of 24 polymorphic fragments with sizes between 139 and 1,468 bp
were amplified. Almost all (95 %) strains showed biofilm formation after 96 h of
incubation. At 96 h of incubation the biofilm-forming strains from the CINVESTAV
collection showed a more heterogeneous ability as biofilms producers. Results
showed a large intra-species genomic variability in Bt. However, some strains
could be correlated as they were found within clusters depending on the location
of isolation.
PMID- 25129642
TI - An unusual presentation of dermatophytosis in a premature infant.
PMID- 25129643
TI - Physical activity modifies the associations between genetic variants and blood
pressure in European adolescents.
AB - We hypothesized that physical activity and sedentary behavior could modify the
associations between known genetic variants blood pressure-associated genes in
European adolescents. Meeting current physical activity recommendations (>= 60
minutes/day) was able attenuate the deleterious effect of the NOS3 rs3918227
polymorphism on systolic blood pressure in European adolescents.
PMID- 25129644
TI - A photoacoustic image reconstruction method using total variation and nonconvex
optimization.
AB - BACKGROUND: In photoacoustic imaging (PAI), the reduction of scanning time is a
major concern for PAI in practice. A popular strategy is to reconstruct the image
from the sparse-view sampling data. However, the insufficient data leads to
reconstruction quality deteriorating. Therefore, it is very important to enhance
the quality of the sparse-view reconstructed images. METHOD: In this paper, we
proposed a joint total variation and Lp-norm (TV-Lp) based image reconstruction
algorithm for PAI. In this algorithm, the reconstructed image is updated by
calculating its total variation value and Lp-norm value. Along with the
iteration, an operator-splitting framework is utilized to reduce the
computational cost and the Barzilai-Borwein step size selection method is adopted
to obtain the faster convergence. RESULTS AND CONCLUSION: Through the numerical
simulation, the proposed algorithm is validated and compared with other widely
used PAI reconstruction algorithms. It is revealed in the simulation result that
the proposed algorithm may be more accurate than the other algorithms. Moreover,
the computational cost, the convergence, the robustness to noises and the tunable
parameters of the algorithm are all discussed respectively. We also implement the
TV-Lp algorithm in the in-vitro experiments to verify its performance in
practice. Through the numerical simulations and in-vitro experiments, it is
demonstrated that the proposed algorithm enhances the quality of the
reconstructed images with faster calculation speed and convergence.
PMID- 25129645
TI - Solubility and release modulation effect of sulfamerazine ternary complexes with
cyclodextrins and meglumine.
AB - This study investigated the effect on solubility and release of ternary complexes
of sulfamerazine (SMR) with beta-(betaCD), methyl-(MbetaCD) and hydroxypropyl
beta-cyclodextrin (HPbetaCD) using meglumine (MEG) as the ternary component. The
combination of MEG with MbetaCD resulted the best approach, with an increased
effect (29-fold) of the aqueous solubility of SMR. The mode of inclusion was
supported by 2D NMR, which indicated that real ternary complexes were formed
between SMR, MEG and MbetaCD or HPbetaCD. Solid state analysis was performed
using Fourier-transform infrared spectroscopy (FT IR), differential scanning
calorimetry (DSC) and powder X-ray diffraction (XRD), which demonstrated that
different interactions occurred among SMR, MEG and MbetaCD or HPbetaCD in the
ternary lyophilized systems. The ternary complexes with betaCD and MbetaCD
produced an additional retention effect on the release of SMR compared to the
corresponding binary complexes, implying that they were clearly superior in terms
of solubility and release modulation.
PMID- 25129646
TI - Localized Pulmonary Edema in the Middle and Inferior Lobes of the Right Lung
after One-lung Ventilation for Minimally Invasive Mitral Valve Surgery.
PMID- 25129647
TI - Pancreatic arteriovenous malformation.
PMID- 25129648
TI - High throughput screening of enzyme activity with mass spectrometry imaging.
AB - Mass spectrometry imaging (MSI) has found a diversity of applications ranging
from localizing metabolites and proteins in tissues to investigating microbial
interactions, and as a result is perhaps the fastest growing subfield of mass
spectrometry. Advances in surface mass spectrometry technologies are equally
applicable to the analysis of arrayed samples. One promising field in which this
capacity has been leveraged is the high-throughput analysis of enzyme activity,
an important step in the development of a wide range of biotechnologies. This
review article describes several emerging approaches that seek to improve the
quality and scope of this application of MSI.
PMID- 25129649
TI - Alpha linolenic acid and oleic acid additively down-regulate malignant potential
and positively cross-regulate AMPK/S6 axis in OE19 and OE33 esophageal cancer
cells.
AB - OBJECTIVE: Both oleic acid (OA) and alpha-linolenic acid (ALA) have been proposed
to down-regulate cell proliferation of prostate, breast, and bladder cancer
cells. However, direct evidence that OA and/or ALA suppresses to the development
of esophageal cancer has not been studied. Also, no previous studies have
evaluated how OA and/or ALA regulates malignant potential (cell proliferation,
migration, colony formation and adhesion) and intracellular signaling pathways,
and whether their effects might be synergistic and/or additive in esophageal
cancer cells has not yet been elucidated. MATERIALS/METHODS: We conducted in
vitro studies and evaluated whether OA and ALA alone or in combination may
regulate malignant potential in OE19 and OE33 esophageal cancer cell lines.
RESULTS: Both OA and ALA significantly down-regulated cell proliferation,
adhesion and/or migration. OA and/or ALA did not change the number of colonies
but decrease colony sizes when compared to control. Also, we observed that OA
and/or ALA positively cross-regulates the expression levels of AMPK/S6 axis.
Moreover, OA and ALA up-regulated tumor suppressor genes (p53, p21, and p27) and
these effects are abolished by AMPK siRNA administration. Importantly, we
observed that these effects are additively regulated by OA and ALA in combination
when compared to control in OE19 and OE33 esophageal cancer cell lines.
CONCLUSIONS: Our novel mechanistic studies provide evidence for an important role
for OA and ALA in esophageal cancer, and suggest that OA and/or ALA might be
useful agents in the management or chemoprevention of esophageal cancer.
PMID- 25129650
TI - Thyroid core needle biopsy: taking stock of the situation.
AB - Recently, the microhistologic evaluation by core needle biopsy (CNB) has been
reported as high accurate to diagnose thyroid nodules with previous indeterminate
or not adequate fine-needle aspiration cytology. In addition, sparse data have
been reported regarding the use of CNB in other conditions. Aim of this review
was to furnish the state of the art of this topic by summarizing published data
about the diagnostic performance of CNB in thyroid lesions, and provide an easy
to use reference for clinical practice. Sources encompass studies published
through May 2014. Original articles were investigated and following specific
aspects were discussed: 1. The "large" needle biopsy in 90's; 2. Complications by
and patient's comfort with thyroid CNB; 3. Advantages provided by examination of
a microhistologic sample of thyroid nodule; 4. Use of CNB in thyroid nodules with
previous not adequate (Thy 1/Class 1/Category I) cytology; 5. Use of CNB in
thyroid neoplasms (Thy 3/Class 3/Category III-IV) cytology; 6. Use of CNB in
specific ultrasonographic presentations of thyroid nodules or in patients with
peculiar clinical contexts; 7. First-line approach by CNB in thyroid nodules; 8.
Immunohistochemistry and molecular tests on CNB samples; and 9. Future
perspective.
PMID- 25129653
TI - Complete band gaps in a polyvinyl chloride (PVC) phononic plate with cross-like
holes: numerical design and experimental verification.
AB - In this work the existence of band gaps in a phononic polyvinyl chloride (PVC)
plate with a square lattice of cross-like holes is numerically and experimentally
investigated. First, a parametric analysis is carried out to find plate thickness
and cross-like holes dimensions capable to nucleate complete band gaps. In this
analysis the band structures of the unitary cell in the first Brillouin zone are
computed by exploiting the Bloch-Floquet theorem. Next, time transient finite
element analyses are performed to highlight the shielding effect of a finite
dimension phononic region, formed by unitary cells arranged into four concentric
square rings, on the propagation of guided waves. Finally, ultrasonic
experimental tests in pitch-catch configuration across the phononic region,
machined on a PVC plate, are executed and analyzed. Very good agreement between
numerical and experimental results are found confirming the existence of the
predicted band gaps.
PMID- 25129651
TI - Growth hormone tumor histological subtypes predict response to surgical and
medical therapy.
AB - Growth hormone (GH) pituitary tumors are associated with significant morbidity
and mortality. Current treatments, including surgery and medical therapy with
somatostatin analogs (SSA), dopamine agonists and/or a GH receptor antagonist,
result in disease remission in approximately half of patients. Predictors of GH
tumor response to different therapies have been incompletely defined based on
histologic subtype, particularly densely (DG) versus sparsely (SG) granulated
adenomas. The aim of this study was to examine our own institutional experience
with GH adenomas and correlate how subtype related to clinical parameters as well
as response to surgery and medical therapies. A retrospective chart review of 101
acromegalic patients operated by a single neurosurgeon was performed. Clinical
data were correlated with histologic subtype and disease control, as defined by
IGF-1 levels, and random growth hormone levels in response to surgery and/or
medical therapies. SG tumors, compared to DG, occurred in younger patients (p =
0.0010), were 3-fold larger (p = 0.0030) but showed no differences in tumor
invasion characteristics (p = 0.12). DG tumors had a higher rate of remission in
response to surgery compared to SG, 65.7 vs. 14.3 % (p < 0.0001), as well as to
medical therapy with SSAs (68.8 % for DG vs. 28.6 % for SG tumors; p = 0.028). SG
tumors not controlled with SSAs consistently responded to a switch to, or
addition of, a GH receptor antagonist. Histological GH tumor subtyping implicates
a different clinical phenotype and biologic behavior, and provides prognostic
significance for surgical success and response to medical therapies.
PMID- 25129654
TI - Altered head orientation patterns in children with idiopathic scoliosis in
conditions with sensory conflict.
AB - PURPOSE: Idiopathic scoliosis (IS) is the most common spinal deformity in
adolescents. Defective postural equilibrium may be a contributing factor. The
information of the three sensory systems combined enables the formation of a
central representation of head position and body posture. Comparison of head
angles of girls with and without scoliosis may result in a difference in head
orientation. METHODS: 25 girls with IS and 16 girls without scoliosis (NS)
between the age of 10-16 years stand in a special constructed box on a roll
tilting platform (tilt -14 degrees to +14 degrees ). RESULTS: NS and IS subjects
behave quite similarly if there is no sensory conflict, but if there is conflict,
the differences between the two groups are greater, especially within the 13- to
14-year-old category. CONCLUSIONS: The differences between groups for different
age categories suggest that the process of development of sensory integration for
estimation of verticality appears to be different for girls with scoliosis.
PMID- 25129652
TI - Steroid replacement in primary adrenal failure does not appear to affect
circulating adipokines.
AB - Despite continuous efforts for an optimal steroid replacement, recent
observations suggest increased cardiometabolic risk and related mortality in
primary adrenal insufficiency (PAI). Adipokines are peptides from the adipose
tissue, markers of cardiometabolic dysfunction. This study was aimed to evaluate
serum levels of adipokines: leptin, adiponectin, and resistin in PAI during
conventional steroid substitution. The analysis comprised 63 patients (mean age
42.7 +/- 14.1 years) and 63 healthy controls. Serum adipokines, lipid profile,
and plasma glucose were assessed in both cohorts. ACTH, serum insulin, HOMA-IR,
DHEA-S, cortisol and 24 h urinary free cortisol were determined in PAI. Body mass
composition was analyzed by Dual-Energy X-ray Absorptiometry. Mean BMI in the
control group was 24.1 +/- 3.9 kg/m(2) and 23.7 +/- 3.9 kg/m(2) in the PAI
cohort. Serum leptin and adiponectin levels were similar in both groups, whereas
resistin appeared significantly lower among affected subjects (p = 0.0002). Its
levels were weakly correlated with HOMA-IR (p = 0.048). Leptin was independently
correlated with fasting insulin, HOMA-IR, BMI, and body fat (p < 0.001). At the
multiple regression analysis only weight (p = 0.017), total and HDL cholesterol
(p < 0.001) appeared significant predictors of adiponectin level. No adipokine
correlations with serum cortisol or daily hydrocortisone dose were found.
Patients receiving DHEA substitution displayed lower leptin and adiponectin
levels (p < 0.05). In conclusion, our study did not provide evidence of an
adverse adipokine profile in patients with PAI under conventional glucocorticoid
replacement. Serum adipokines in treated PAI follow similar correlations to those
reported in healthy subjects. Further prospective studies are warranted to verify
and explain plausible excess of cardiovascular mortality in PAI.
PMID- 25129655
TI - Volumetric three-dimensional computed tomographic evaluation of the upper airway
in patients with obstructive sleep apnoea syndrome treated by maxillomandibular
advancement.
AB - Obstructive sleep apnoea syndrome is the periodic reduction or cessation of
airflow during sleep together with daytime sleepiness. Its diagnosis requires
polysomnographic evidence of 5 or more episodes of apnoea or hypopnoea/hour of
sleep (apnoea/hypopnoea index, AHI). Volumetric 3-dimensional computed
tomographic (CT) reconstruction enables the accurate measurement of the volume of
the airway. Nasal continuous positive airway pressure (CPAP) is the conventional
non-surgical treatment for patients with severe disease. Operations on the soft
tissues that are currently available give success rates of only 40%-60%.
Maxillomandibular advancement is currently the most effective craniofacial
surgical technique for the treatment of obstructive sleep apnoea in adults.
However, the appropriate distance for advancement has not been established.
Expansion of the air-flow column volume did not result in an additional reduction
in AHI, which raises the important issue of how much the maxillomandibular
complex should be advanced to obtain an adequate reduction in AHI while avoiding
the risks of overexpansion or underexpansion. We have shown that there is a
significant linear relation between increased absolute upper airway volume after
advancement and improvement in the AHI (p=0.013). However, increases in upper
airway volume of 70% or more achieved no further reduction in the AHI, which
suggests that the clinical improvement in AHI reaches a plateau, and renders
further expansion unnecessary. This gives a new perspective to treatment based on
the prediction of changes in volume, so the amount of sagittal advancement can be
tailored in each case, which replaces the current standard of 1cm.
PMID- 25129657
TI - [Effects of air pollution on mortality. Comments].
PMID- 25129658
TI - [Insulin treatment in patients over 80 years old and the risk of hypoglycemia].
PMID- 25129656
TI - Dietary fiber intake and its association with indicators of adiposity and serum
biomarkers in European adolescents: the HELENA study.
AB - PURPOSE: To evaluate total, energy-adjusted dietary fiber (DF), water-soluble
fiber (WSF), and water-insoluble fiber (WIF) intakes in European adolescents and
to investigate their association with indicators of adiposity and serum
biomarkers. METHODS: This study, conducted from 2006 to 2007, included 1804
adolescents aged 12.5-17.5 years (47% males) from eight European cities
completing two non-consecutive computerized 24-h dietary recalls. GLM
multivariate analysis was used to investigate associations. RESULTS: Mean DF
intake (20 g/day) of the sample met the European Food Safety Authority
recommendation, but was below those of the World Health Organization and of the
Institute of Medicine. Total DF, WSF and WIF intakes were higher in males (P <
0.001), but following energy-adjustments significantly higher intakes were
observed among females (P < 0.001). Bread and cereals contributed most to total
DF, WSF and WIF intakes, followed by potatoes and grains, energy-dense but low
nutritious foods, fruits and vegetables. Moreover, energy-adjusted WSF and WIF
were positively associated with body fat percentage (BF%), waist to height ratio
and low-density lipoprotein cholesterol, while energy-adjusted WSF was inversely
associated with serum fasting glucose (beta = -0. 010, P = 0.020). CONCLUSION:
Total DF intakes are rather low in European adolescents. An inverse association
with serum fasting glucose might indicate a possible beneficial role of DF in
preventing insulin resistance and its concomitant diseases, even though DF
intakes were positively associated with adolescents' BF%. Therefore, further
longitudinal studies should elaborate on these potential beneficial effects of DF
intake in the prevention of obesity and related chronic diseases.
PMID- 25129659
TI - Structural and dynamical properties of Li+-dibenzo-18-crown-6(DB18C6) complex in
pure solvents and at the aqueous-organic interface.
AB - Microstructure of dibenzo-18-crown-6 (DB18C6) and DB18C6/Li(+) complex in
different solvents (water, methanol, chloroform, and nitrobenzene) have been
analyzed using radial distribution function (RDF), coordination number (CN), and
orientation profiles, in order to identify the role of solvents on complexation
of DB18C6 with Li(+), using molecular dynamics (MD) simulations. In contrast to
aqueous solution of LiCl, no clear solvation pattern is found around Li(+) in the
presence of DB18C6. The effect of DB18C6 has been visualized in terms of
reduction in peak height and shift in peak positions of g(Li-Ow). The appearance
of damped oscillations in velocity autocorrelation function (VACF) of complexed
Li(+) described the high frequency motion to a "rattling" of the ion in the cage
of DB18C6. The solvent-complex interaction is found to be higher for water and
methanol due to hydrogen bond (HB) interactions with DB18C6. However, the
stability of DB18C6/Li(+) complex is found to be almost similar for each solvent
due to weak complex-solvent interactions. Further, Li(+) complex of DB18C6 at the
liquid/liquid interface of two immiscible solvents confirm the high interfacial
activity of DB18C6 and DB18C6/Li(+) complex. The complexed Li(+) shows higher
affinity for water than organic solvents; still they remain at the interface
rather than migrating toward water due to higher surface tension of water as
compared to organic solvents. These simulation results shed light on the role of
counter-ions and spatial orientation of species in pure and hybrid solvents in
the complexation of DB18C6 with Li(+).
PMID- 25129660
TI - Computational investigation of interaction of polypyrrole on the surface of
single-walled carbon nanotube.
AB - A density functional theory investigation of adsorption of monomer, dimer and
trimer forms of pyrrole on the outer surface of zigzag (7,0) single-walled carbon
nanotube (SWCNT) has been reported. Geometries of the complexes were optimized
using the M06-2X functional and the 6-31G(d,p) basis set. Moreover, 6-311G(d,p),
cc-pVDZ and cc-pVTZ basis sets were used for the adsorption energy calculation
and such energies were corrected for the basis set superposition error. Vertical
ionization potential and electron affinity of the investigated system were also
computed. The interaction of polypyrrole on the SWCNT surface is characterized by
the stacking interaction. Adsorption (binding) energy of pyrrole on the SWCNT
surface is weak, but such energy increases with the number of monomer units in
the pyrrole oligomer. In the SWCNT-pyrrole complexes, the oxidation and reduction
processes will take place only at the SWCNT. The influence of larger unit on the
electronic properties of the complex has been detailed.
PMID- 25129661
TI - Theoretical investigation of the mechanisms and dynamics of the reaction CHF2OCF
2CHFCl+Cl.
AB - The reaction of CHF2OCF2CHFCl with atomic chlorine was studied using B3LYP/6
311G(d,p), BHandHLYP/6-311G(d,p), and M06-2X/6-311G(d,p) methods and further
using CCSD(T) and QCISD(T) methods. Two hydrogen abstraction channels were found
for the title reaction. Dynamics calculations were followed by means of canonical
variational transition state with the small-curvature tunneling correction
between 220 and 2,000 K. Our rate constant k = 2.90 * 10(-15) cm(3) molecule(-1)
s(-1) is in reasonable agreement with the available data (3.20 +/- 0.32) * 10(
15) cm(3) molecule(-1) s(-1) at 296 K. The three-parameter Arrhenius expression
(in the unit of cm(3) molecule(-1) s(-1)) for the title reaction is given as k
(T) = 1.38 * 10 (-19) T (2.57) exp (-2622.95/T).
PMID- 25129662
TI - Evidence of a long C-C attractive interaction in cerussite mineral: QTAIM and ELF
analyses.
AB - Cerussite, an orthorhombic lead carbonate mineral, has a structure and physical
properties that cannot be understood merely in terms of ionic anion-cation
interactions. The nature of the chemical bonding in cerussite is analyzed by
means of the quantum theory of atoms in molecules (QTAIM) and the analysis of the
electron localization function (ELF). A long C-C attractive interaction (3.077 A)
along the c axis of the cerussite structure is evidenced by the presence of bond
critical points between the C atoms of the CO(3)(2-) molecular groups. It is
proposed that the Pb-O interactions, which are mostly ionic in nature, disturb
the structure of the CO(3)(2-) molecular groups and promote their interaction
along the c axis. The importance of this long-range interaction in the high
pressure crystal chemistry of carbonate minerals and in the explanation of some
crystal growth features observed for orthorhombic carbonates is also discussed in
this work.
PMID- 25129663
TI - Transcaval retrograde transcatheter aortic valve replacement for patients with no
other access: first-in-man experience with CoreValve.
PMID- 25129665
TI - Fluoroscopic anatomy of left-sided heart structures for transcatheter
interventions: insight from multislice computed tomography.
AB - With the introduction of transcatheter structural heart therapies, cardiologists
are increasingly aware of the importance of understanding anatomical details of
left-sided heart structures. Understanding fluoroscopic cardiac anatomy can
facilitate optimal positioning and deployment of prostheses during transcatheter
valve repair/replacement, left atrial appendage occlusion, septal defect closure,
and paravalvular leak closure. It is possible to use multislice computed
tomography to determine optimal fluoroscopic viewing angles for such
transcatheter therapies. The purpose of this paper is to describe how optimal
fluoroscopic viewing angles of left-sided heart structures can be obtained using
computed tomography. Two- and 3-chamber views are described and may become
standard in the context of transcatheter structural heart interventions.
PMID- 25129666
TI - Real-time assessment of myocardial viability in the catheterization laboratory
using the intracoronary electrograms recorded by the PTCA guidewire in patients
with left ventricular dysfunction: comparison with delayed-enhancement magnetic
resonance imaging.
AB - OBJECTIVES: This study aimed to determine whether the intracoronary electrograms
(IC-EGMs) recorded using a standard percutaneous coronary intervention guidewire
could provide myocardial viability information. BACKGROUND: The revascularization
of dysfunctional but viable myocardium may confer prognostic benefits compared
with medical therapy in patients with post-ischemic heart failure. However,
knowledge of myocardial viability is often unavailable at the time of the
procedure. METHODS: The peak-to-peak voltage of 317 IC-EGMs recordings from 25
patients with a previous myocardial infarction and systolic dysfunction were
matched with corresponding delayed-enhancement magnetic resonance imaging sites
using a 17-segment model of the left ventricle. RESULTS: Sixty-seven recordings
were obtained from segments classified as complete scar on delayed-enhancement
magnetic resonance imaging (group A), 162 from partially viable segments (group
B), and 88 from fully viable segments (group C). Three high-pass (HP) filters
(0.5, 30, and 100 Hz) were applied to the signals to modulate their spatial
resolution. For all filters, the peak-to-peak voltage significantly decreased
from group C to group B to group A (p < 0.001 for all comparisons). When receiver
operating characteristic analysis was used to compare nonviable (group A) with
viable (group B + C) segments, the optimal discriminating voltages were 4.6, 2.2,
and 0.78 mV for, respectively, HP-0.5, HP-30, and HP-100 filters, with a
sensitivity of 92%, 94%, and 99% and a specificity of 70%, 79%, and 69%.
CONCLUSIONS: The amplitude of the IC-EGMs discriminates viable from nonviable
left ventricular segments. Because this technique is simple and inexpensive and
provides real-time results, it is potentially useful to aid decision making in
the catheterization laboratory.
PMID- 25129664
TI - Mechanisms of atherothrombosis and vascular response to primary percutaneous
coronary intervention in women versus men with acute myocardial infarction:
results of the OCTAVIA study.
AB - OBJECTIVES: This study sought to assess in vivo sex differences in the
pathophysiology of ST-segment elevation myocardial infarction (STEMI) and
vascular response to primary percutaneous coronary intervention (PCI).
BACKGROUND: There is no consensus on whether differences in the pathophysiology
of STEMI and response to primary PCI between women and men reflect biological
factors as opposed to differences in age. METHODS: In this prospective,
multicenter study, 140 age-matched men and women with STEMI undergoing primary
PCI with everolimus-eluting stent were investigated with intravascular optical
coherence tomography, histopathology-immunohistochemistry of thrombus aspirates,
and serum biomarkers. Primary endpoints were the percentages of culprit plaque
rupture at baseline and everolimus-eluting stent strut coverage at 9-month follow
up as determined by optical coherence tomography. RESULTS: Men and women had
similar rates of plaque rupture (50.0% vs. 48.4%; risk ratio [RR]: 1.03; 95%
confidence interval [CI]: 0.73 to 1.47; p = 0.56). Nonruptured/eroded plaques
comprised 25% of all cases (p = 0.86 in men vs. women). There were no sex
differences in composition of aspirated thrombus and immune and inflammatory
serum biomarkers. At 9 months, women had similar strut coverage (90.9% vs. 92.5%;
difference in medians: RR: 0.2%; 95% CI: -0.4% to 1.3%; p = 0.89) and amount of
in-stent neointimal obstruction (10.3% vs. 10.6%; p = 0.76) as men did. There
were no sex differences in clinical outcome either at 30-day or 1-year follow-up.
CONCLUSIONS: In patients presenting with STEMI undergoing primary PCI, no
differences in culprit plaque morphology and factors associated with coronary
thrombosis were observed between age-matched men and women. Women also showed
similar vascular healing response to everolimus-eluting stents as men did.
(Optical Coherence Tomography Assessment of Gender Diversity In Primary
Angioplasty: The OCTAVIA Trial [OCTAVIA]; NCT01377207).
PMID- 25129667
TI - Thrombus formation at the MitraClip system during percutaneous mitral valve
repair.
PMID- 25129668
TI - Transapical transcatheter aortic valve for severe aortic regurgitation: expanding
the limits.
AB - OBJECTIVES: This study sought to evaluate the self-expandable ACURATE TA device
(Symetis SA, Ecublens, Switzerland) in a cohort of patients with pure aortic
regurgitation (AR). BACKGROUND: Transcatheter aortic valve replacement (TAVR) has
been initially considered as an alternative for high-risk patients with aortic
stenosis. Although the current experience is limited, TAVR might be also an
alternative to treat patients with pure, severe AR. METHODS: Between April 2012
and December 2013, a total of 8 high-risk patients with pure, severe AR were
enrolled (grade III+). Clinical and hemodynamic data as well as data on device
and procedure parameters and outcomes were collected. RESULTS: Patient mean was
72.5 +/- 8.4 years, and 37.5% of patients were female. Logistic EuroSCORE was
34.0 +/- 7.9% and the Society of Thoracic Surgeons score was 7.3 +/- 3.3% on
average. Two patients had undergone emergency aortic operation before due to
acute type A aortic dissection, and both were treated by replacement of the
ascending aorta (including root reconstruction) and the aortic arch combined with
or without E-vita Open stent graft (Jotec GmbH, Hechingen, Germany) (January 2011
and March 2012), whereas the other patients experienced primary AR. All patients
underwent successful transapical TAVR with the transapical ACURATE TA device
(size small, n = 1, size medium, n = 3, size large, n = 4) without any
intraprocedural complications according to the Valve Academic Research Consortium
2 criteria. Post-procedure AR grade I+ or lower, as revealed by transoesophageal
echocardiography and angiography, was present in all 8 patients. At 30 days, the
stroke incidence and all-cause mortality rate were 0%. CONCLUSIONS: This small
single-center series demonstrates the feasibility of transapical TAVR with the
self-expandable ACURATE TA device in high-risk patients with severe AR.
PMID- 25129669
TI - Left anterior descending coronary artery occlusion during transcatheter pulmonary
valve implantation: successful rescue percutaneous revascularization.
PMID- 25129670
TI - Contralateral embolization of intima after transfemoral aortic valve replacement.
PMID- 25129671
TI - Instant stent-accentuated 3-dimensional optical coherence tomography of a
bifurcation lesion treated with reverse minimum overlapping culotte stenting.
PMID- 25129672
TI - Initial German experience with transapical implantation of a second-generation
transcatheter heart valve for the treatment of aortic regurgitation.
AB - OBJECTIVES: This analysis reports on the initial German multicenter experience
with the JenaValve (JenaValve Technology GmbH, Munich, Germany) transcatheter
heart valve for the treatment of pure aortic regurgitation. BACKGROUND:
Experience with transcatheter aortic valve implantation (TAVI) for severe aortic
regurgitation is limited due to the risk of insufficient anchoring of the valve
stent within the noncalcified aortic annulus. METHODS: Transapical TAVI with a
JenaValve for the treatment of severe aortic regurgitation was performed in 31
patients (age 73.8 +/- 9.1 years) in 9 German centers. All patients were
considered high risk for surgery (logistic EuroSCORE [European System for Cardiac
Operative Risk Evaluation] 23.6 +/- 14.5%) according to a local heart team
consensus. Procedural results and clinical outcomes up to 6 months were analyzed.
RESULTS: Implantation was successful in 30 of 31 cases (aortic annulus diameter
24.7 +/- 1.5 mm); transcatheter heart valve dislodgement necessitated valve-in
valve implantation in 1 patient. Post-procedural aortic regurgitation was
none/trace in 28 of 31 and mild in 3 of 31 patients. During follow-up, 2 patients
underwent valvular reinterventions (surgical aortic valve replacement for
endocarditis, valve-in-valve implantation for increasing paravalvular
regurgitation). All-cause mortality was 12.9% and 19.3% at 30 days and 6 months,
respectively. In the remaining patients, a significant improvement in New York
Heart Association class was observed and persisted up to 6 months after TAVI.
CONCLUSIONS: Aortic regurgitation remains a challenging pathology for TAVI. After
initial demonstration of feasibility, this multicenter study revealed the
JenaValve transcatheter heart valve as a reasonable option in this subset of
patients. However, a significant early noncardiac mortality related to the high
risk population emphasizes the need for careful patient selection.
PMID- 25129673
TI - Impact of combined prenatal ethanol and prenatal stress exposures on markers of
activity-dependent synaptic plasticity in rat dentate gyrus.
AB - Prenatal ethanol exposure and prenatal stress can each cause long-lasting
deficits in hippocampal synaptic plasticity and disrupt learning and memory
processes. However, the mechanisms underlying these perturbations following a
learning event are still poorly understood. We examined the effects of prenatal
ethanol exposure and prenatal stress exposure, either alone or in combination, on
the cytosolic expression of activity-regulated cytoskeletal (ARC) protein and the
synaptosomal expression of AMPA-glutamate receptor subunits (GluA1 and GluA2) in
dentate gyrus of female adult offspring under baseline conditions and after 2
trial trace conditioning (TTTC). Surprisingly, baseline cytoplasmic ARC
expression was significantly elevated in both prenatal treatment groups. In
contrast, synaptosomal GluA1 receptor subunit expression was decreased in both
prenatal treatment groups. GluA2 subunit expression was elevated in the prenatal
stress group. TTTC did not alter ARC levels compared to an unpaired behavioral
control (UPC) group in any of the 4 prenatal treatment groups. In contrast, TTTC
significantly elevated both synaptosomal GluA1 and GluA2 subunit expression
relative to the UPC group in control offspring, an effect that was not observed
in any of the other 3 prenatal treatment groups. Given ARC's role in regulating
synaptosomal AMPA receptors, these results suggest that prenatal ethanol-induced
or prenatal stress exposure-induced increases in baseline ARC levels could
contribute to reductions in both baseline and activity-dependent changes in AMPA
receptors in a manner that diminishes the role of AMPA receptors in dentate gyrus
synaptic plasticity and hippocampal-sensitive learning.
PMID- 25129675
TI - Diminished reliability of tryptase as risk indicator of mastocytosis in older
overweight subjects.
AB - BACKGROUND: Currently, measurement of serum tryptase level is the most commonly
used test to estimate the need for bone marrow biopsy in patients suspected to
have indolent systemic mastocytosis (ISM). Yet tryptase levels do not solely
reflect the mast cell load and can be elevated by overweight, older age, and
impaired renal function. The influence of these factors on urinary
methylhistamine (MH) and methylimidazole acetic acid (MIMA) is still unknown.
OBJECTIVE: We investigated the impact of age, body mass index (BMI), and kidney
function on the diagnostic accuracy of tryptase, MH, and MIMA to select the most
optimal test indicating the necessity of a bone marrow biopsy in ISM-suspected
patients. METHODS: Retrospective data analysis of all adults in whom bone marrow
investigations were performed because of high clinical suspicion and/or elevated
tryptase, MH, or MIMA. RESULTS: 194 subjects were included. ISM was present in
112 and absent in 82 subjects (non-ISM). Tryptase was elevated by age and body
weight in non-ISM subjects and by BMI in ISM subjects; however, these factors did
not influence MH or MIMA. In the total study population, the diagnostic accuracy
of tryptase, MH, and MIMA were comparable (area under the curve 0.80, 0.80, and
0.83). In subjects >50 years with a BMI >25 kg/m(2), the diagnostic accuracy of
MIMA was higher compared with that of tryptase (area under the curve 0.93 vs
0.74; P = .011). CONCLUSION: In ISM-suspected patients >50 years with a BMI of
>25 kg/m(2), MIMA has a greater value compared with tryptase in estimating the
need for bone marrow biopsy.
PMID- 25129676
TI - B-cell linear epitopes mapping of antigen-5 allergen from Polybia paulista wasp
venom.
PMID- 25129674
TI - Ethanol treatment of lymphoblastoid cell lines from alcoholics and non-alcoholics
causes many subtle changes in gene expression.
AB - To elucidate the effects of a controlled exposure to ethanol on gene expression,
we studied lymphoblastoid cell lines (LCLs) from 21 alcoholics and 21 controls.
We cultured each cell line for 24 h with and without 75 mM ethanol and measured
gene expression using microarrays. Differences in expression between LCLs from
alcoholics and controls included 13 genes previously identified as associated
with alcoholism or related traits, including KCNA3, DICER1, ZNF415, CAT, SLC9A9,
and PPARGC1B. The paired design allowed us to detect very small changes due to
ethanol treatment: ethanol altered the expression of 37% of the probe sets (51%
of the unique named genes) expressed in these LCLs, most by modest amounts.
Ninety-nine percent of the named genes expressed in the LCLs were also expressed
in brain. Key pathways affected by ethanol include cytokine, TNF, and NFkappaB
signaling. Among the genes affected by ethanol were ANK3, EPHB1, SLC1A1, SLC9A9,
NRD1, and SH3BP5, which were reported to be associated with alcoholism or related
phenotypes in 2 genome-wide association studies. Genes that either differed in
expression between alcoholics and controls or were affected by ethanol exposure
are candidates for further study.
PMID- 25129677
TI - Influence of early-life exposures on food sensitization and food allergy in an
inner-city birth cohort.
AB - OBJECTIVE: Previous data suggest that food allergy (FA) might be more common in
inner-city children; however, these studies have not collected data on both
sensitization and clinical reactivity or early-life exposures. METHODS: Children
in the Urban Environment and Childhood Asthma birth cohort were followed through
age 5 years. Household exposures, diet, clinical history, and physical
examinations were assessed yearly; levels of specific IgE to milk, egg, and
peanut were measured at 1, 2, 3, and 5 years of age. On the basis of
sensitization (IgE >=0.35 kU/L) and clinical history over the 5-year period,
children were classified as having FA or being possibly allergic, sensitized but
tolerant, or not allergic/not sensitized. RESULTS: Five hundred sixteen children
were included. Overall, 55.4% were sensitized (milk, 46.7%; egg, 31.0%; and
peanut, 20.9%), whereas 9.9% were categorized as having FA (peanut, 6.0%; egg,
4.3%; and milk, 2.7%; 2.5% to >1 food). The remaining children were categorized
as possibly allergic (17.0%), sensitized but tolerant (28.5%), and not sensitized
(44.6%). Eighteen (3.5%) reported reactions to foods for which IgE levels were
not measured. Food-specific IgE levels were similar in children with FA versus
sensitized but tolerant children, except for egg, levels of which were higher in
patients with FA at ages 1 and 2 years. FA was associated with recurrent wheeze,
eczema, aeroallergen sensitization, male sex, breast-feeding, and lower endotoxin
exposure in year 1 but not with race/ethnicity, income, tobacco exposure,
maternal stress, or early introduction of solid foods. CONCLUSIONS: Even given
that this was designed to be a high-risk cohort, the cumulative incidence of FA
is extremely high, especially considering the strict definition of FA that was
applied and that only 3 common allergens were included.
PMID- 25129678
TI - Biological clustering supports both "Dutch" and "British" hypotheses of asthma
and chronic obstructive pulmonary disease.
AB - BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are
heterogeneous diseases. OBJECTIVE: We sought to determine, in terms of their
sputum cellular and mediator profiles, the extent to which they represent
distinct or overlapping conditions supporting either the "British" or "Dutch"
hypotheses of airway disease pathogenesis. METHODS: We compared the clinical and
physiological characteristics and sputum mediators between 86 subjects with
severe asthma and 75 with moderate-to-severe COPD. Biological subgroups were
determined using factor and cluster analyses on 18 sputum cytokines. The
subgroups were validated on independent severe asthma (n = 166) and COPD (n = 58)
cohorts. Two techniques were used to assign the validation subjects to subgroups:
linear discriminant analysis, or the best identified discriminator (single
cytokine) in combination with subject disease status (asthma or COPD). RESULTS:
Discriminant analysis distinguished severe asthma from COPD completely using a
combination of clinical and biological variables. Factor and cluster analyses of
the sputum cytokine profiles revealed 3 biological clusters: cluster 1: asthma
predominant, eosinophilic, high TH2 cytokines; cluster 2: asthma and COPD
overlap, neutrophilic; cluster 3: COPD predominant, mixed eosinophilic and
neutrophilic. Validation subjects were classified into 3 subgroups using
discriminant analysis, or disease status with a binary assessment of sputum IL
1beta expression. Sputum cellular and cytokine profiles of the validation
subgroups were similar to the subgroups from the test study. CONCLUSIONS: Sputum
cytokine profiling can determine distinct and overlapping groups of subjects with
asthma and COPD, supporting both the British and Dutch hypotheses. These findings
may contribute to improved patient classification to enable stratified medicine.
PMID- 25129679
TI - Total transcriptome, proteome, and allergome of Johnson grass pollen, which is
important for allergic rhinitis in subtropical regions.
AB - BACKGROUND: Genomic data are lacking for many allergen sources. To circumvent
this limitation, we implemented a strategy to reveal the repertoire of pollen
allergens of a grass with clinical importance in subtropical regions, where an
increasing proportion of the world's population resides. OBJECTIVE: We sought to
identify and immunologically characterize the allergenic components of the
Panicoideae Johnson grass pollen (JGP; Sorghum halepense). METHODS: The total
pollen transcriptome, proteome, and allergome of JGP were documented. Serum IgE
reactivities with pollen and purified allergens were assessed in 64 patients with
grass pollen allergy from a subtropical region. RESULTS: Purified Sor h 1 and Sor
h 13 were identified as clinically important allergen components of JGP with
serum IgE reactivity in 49 (76%) and 28 (43.8%), respectively, of patients with
grass pollen allergy. Within whole JGP, multiple cDNA transcripts and peptide
spectra belonging to grass pollen allergen families 1, 2, 4, 7, 11, 12, 13, and
25 were identified. Pollen allergens restricted to subtropical grasses (groups 22
24) were also present within the JGP transcriptome and proteome. Mass
spectrometry confirmed the IgE-reactive components of JGP included isoforms of
Sor h 1, Sor h 2, Sor h 13, and Sor h 23. CONCLUSION: Our integrated molecular
approach revealed qualitative differences between the allergenic components of
JGP and temperate grass pollens. Knowledge of these newly identified allergens
has the potential to improve specific diagnosis and allergen immunotherapy
treatment for patients with grass pollen allergy in subtropical regions and
reduce the burden of allergic respiratory disease globally.
PMID- 25129682
TI - Sputum adiponectin as a marker for western red cedar asthma.
PMID- 25129681
TI - Short- and long-term efficacy of prednisolone for first acute rhinovirus-induced
wheezing episode.
AB - BACKGROUND: Rhinovirus-induced wheezing is an important risk factor for recurrent
wheezing. There are no randomized controlled trials on the effect of systemic
corticosteroids in patients with this disease. OBJECTIVE: We sought to study the
short- and long-term effects of prednisolone treatment of the first acute,
moderate-to-severe, rhinovirus-induced wheezing episode in young children.
METHODS: After confirming rhinovirus from nasopharyngeal aspirate by using PCR,
79 children with a first wheezing episode at age 3 to 23 months were randomized
to receive oral prednisolone (first dose of 2 mg/kg, followed by 2 mg/kg/d in 2
divided doses for 3 days) or placebo. The trial was double blind throughout the
12-month follow-up. The primary outcomes were long term: new physician-confirmed
wheezing episode within 2 months, number of physician-confirmed wheezing episodes
within 12 months, and initiation of regular controller medication for asthma
symptoms within 12 months. The primary interaction analysis examined rhinovirus
load. RESULTS: Seventy-four patients completed the study (mean age, 13 months;
28% atopic). Long-term outcomes did not differ between groups (all P >= .30). For
short-term outcomes, the prednisolone group had less cough, rhinitis, noisy
breathing, severe breathing difficulties, and nocturnal respiratory symptoms at
home within 2 weeks (all P < .05). The 25 children with greater than 7000
rhinovirus copies/mL (most sensitive cutoff) benefitted from prednisolone in
terms of less risk of physician-confirmed recurrence within 2 and 12 months
compared with placebo (both P < .05). CONCLUSIONS: Prednisolone cannot be
routinely recommended for all young children experiencing their first acute,
moderate-to-severe, rhinovirus-induced wheezing episode. Prednisolone might be
beneficial in a subgroup of children with high viral loads.
PMID- 25129680
TI - Eosinophil-dependent skin innervation and itching following contact toxicant
exposure in mice.
AB - BACKGROUND: Contact toxicant reactions are accompanied by localized skin
inflammation and concomitant increases in site-specific itch responses. The
role(s) of eosinophils in these reactions is poorly understood. However, previous
studies have suggested that localized eosinophil-nerve interactions at sites of
inflammation significantly alter tissue innervation. OBJECTIVE: To define a
potential mechanistic link between eosinophils and neurosensory responses in the
skin leading to itching. METHODS: BALB/cJ mice were exposed to different contact
toxicants, identifying trimellitic anhydride (TMA) for further study on the basis
of inducing a robust eosinophilia accompanied by degranulation. Subsequent
studies using TMA were performed with wild type versus eosinophil-deficient PHIL
mice, assessing edematous responses and remodeling events such as sensory nerve
innervation of the skin and induced pathophysiological responses (ie, itching).
RESULTS: Exposure to TMA, but not dinitrofluorobenzene, resulted in a robust
eosinophil skin infiltrate accompanied by significant levels of degranulation.
Follow-up studies using TMA with wild type versus eosinophil-deficient PHIL mice
showed that the induced edematous responses and histopathology were, in part,
causatively linked with the presence of eosinophils. Significantly, these data
also demonstrated that eosinophil-mediated events correlated with a significant
increase in substance P content of the cutaneous nerves and an accompanying
increase in itching, both of which were abolished in the absence of eosinophils.
CONCLUSIONS: Eosinophil-mediated events following TMA contact toxicant reactions
increase skin sensory nerve substance P and, in turn, increase itching responses.
Thus, eosinophil-nerve interactions provide a potential mechanistic link between
eosinophil-mediated events and neurosensory responses following exposure to some
contact toxicants.
PMID- 25129684
TI - The structure and validity of directional measures of appearance social
comparison among emerging adults in China.
AB - We evaluated the structure and validity of the Upward Appearance Comparison Scale
(UPACS) and Downward Appearance Comparison Scale (DACS) (O'Brien et al., 2009) in
Chinese samples. In Study 1, principal component analysis on an initial sample
(427 women, 123 men) and confirmatory factor analysis on another sample (447
women, 121 men) found that a 15-item, two component model had the best overall
fit. Derived components had moderate correlations with most conceptually related
measures and low correlations with less conceptually related indices. Study 2
participants (310 women, 201 men) completed the UPACS and DACS as well as
measures of disordered eating, fatness concern, and negative affect; they were re
assessed one year later. Baseline UPACS scores predicted changes in disordered
eating for women and fatness concerns for men, independent of initial
disturbances, but DACS responses were not related to outcomes. Findings
highlighted the potential utility of derived UPACS and DACS within a Chinese
context.
PMID- 25129685
TI - "Appearance potent"? A content analysis of UK gay and straight men's magazines.
AB - With little actual appraisal, a more 'appearance potent' (i.e., a reverence for
appearance ideals) subculture has been used to explain gay men's greater body
dissatisfaction in comparison to straight men's. This study sought to assess the
respective appearance potency of each subculture by a content analysis of 32
issues of the most read gay (Attitude, Gay Times) and straight men's magazines
(Men's Health, FHM) in the UK. Images of men and women were coded for their
physical characteristics, objectification and nudity, as were the number of
appearance adverts and articles. The gay men's magazines featured more images of
men that were appearance ideal, nude and sexualized than the straight men's
magazines. The converse was true for the images of women and appearance adverts.
Although more research is needed to understand the effect of this content on the
viewer, the findings are consistent with a more appearance potent gay male
subculture.
PMID- 25129683
TI - Stress and asthma: novel insights on genetic, epigenetic, and immunologic
mechanisms.
AB - In the United States the economically disadvantaged and some ethnic minorities
are often exposed to chronic psychosocial stressors and disproportionately
affected by asthma. Current evidence suggests a causal association between
chronic psychosocial stress and asthma or asthma morbidity. Recent findings
suggest potential mechanisms underlying this association, including changes in
the methylation and expression of genes that regulate behavioral, autonomic,
neuroendocrine, and immunologic responses to stress. There is also evidence
suggesting the existence of susceptibility genes that predispose chronically
stressed youth to both post-traumatic stress disorder and asthma. In this review
we critically examine published evidence and suggest future directions for
research in this field.
PMID- 25129687
TI - Editorial overview: Mechanisms: Chemical and computational probes of biological
mechanism.
PMID- 25129686
TI - The role of media and peer influences in Australian women's attitudes towards
cosmetic surgery.
AB - The study aimed to examine the influence of media and peers on attitudes towards
cosmetic surgery using a sociocultural framework. A sample of 351 Australian
women aged 18-69 years completed measures of media exposure, friend
conversations, internalisation of appearance ideals, appearance comparison, body
dissatisfaction, and attitudes towards cosmetic surgery. Correlational analysis
showed that almost all media and friend variables were significantly correlated
with positive attitudes towards cosmetic surgery. A structural equation model
based on the sociocultural model showed a good level of fit to the data. The
effects of media exposure and friend conversations on body dissatisfaction and
attitudes towards cosmetic surgery were mediated by internalisation. We concluded
that media exposure and friend conversations affected attitudes towards cosmetic
surgery both directly and indirectly. Our results contribute to the understanding
of the sociocultural mechanisms underlying women's motivations for cosmetic
surgery.
PMID- 25129688
TI - A pitfall in diagnosing Cushing's disease: ectopic ACTH-producing pituitary
adenoma in the sphenoid sinus.
AB - PURPOSE: To show a rare case of Cushing's disease and possible cause of failed
transsphenoidal surgery. METHOD: We report on a 50-year-old woman suffering from
ACTH-dependent Cushing's syndrome. Endocrinological work-up including low
dose/high-dose dexamethasone test (Liddle-test) and CRH test were clearly
compatible with pituitary origin. Although an MRI showed no pituitary tumor, CRH
stimulated petrosal sinus sampling revealed a significant central-peripheral
gradient in ACTH concentrations, rendering Cushing's disease very likely. The
patient underwent transsphenoidal surgery with negative exploration of the
pituitary gland. After intraoperative re-evaluation of the preoperative MRI, a
"polyp" at the bottom of the sphenoid sinus was identified. The intraoperative
microscopic aspect as well as instantaneous sections and cytology of a biopsy
confirmed an adenoma, which was then removed. Histological analysis demonstrated
an ACTH-producing pituitary adenoma adjacent to respiratory mucous membrane
consisting of ciliated epithelium with submucous connective tissue.
Postoperatively, ACTH concentrations were decreased and intermittent
hydrocortisone substitution treatment was initiated. At the 3-month follow up,
Cushing's stigmata were found to be alleviated and the hydrocortisone dosage
could be reduced. CONCLUSION: Ectopic pituitary adenoma tissue causing Cushing's
disease is extremely rare but a potential cause for surgical failure or re
evaluation.
PMID- 25129689
TI - Effects of introducing Xpert MTB/RIF test on multi-drug resistant tuberculosis
diagnosis in KwaZulu-Natal South Africa.
AB - BACKGROUND: An algorithm instituted following Xpert MTB/RIF (Xpert) introduction
in South Africa advocates for treating all Xpert rifampicin resistant patients as
MDR-TB cases while awaiting confirmation by phenotypic or genotypic drug
susceptibility testing. This study evaluates how the Xpert has influenced the
diagnosis and management of drug resistant TB in the highest burdened district of
KwaZulu-Natal Province. METHODS: Data was retrospectively collected from all
patients with rifampicin resistance on Xpert performed between March 2011 and
April 2012. Xpert results were compared with those of phenotypic and/genotypic
drug susceptibility testing. Patients' records were used to determine the time to
treatment initiation. RESULTS: Out of 637 patients tested by Xpert, 50% had
confirmatory results, of which a third were sent on the same day as Xpert test.
The rate of rifampicin discordance and monoresistance was 8.8% and 13.4%
respectively and there was no difference between phenotypic and genotypic
confirmation. Among those who had been initiated on treatment, 28%, 40%, 21% and
8% of patients commenced within 2 weeks, 1 month, 2 months and 3 months of Xpert
testing respectively, while the remaining 3% were observed without treatment.
CONCLUSION: This study emphasizes the importance of complying with the algorithm
in confirming all Xpert rif resistant cases so as to ensure proper management of
these patients. Despite the rapidity of the Xpert results, only about 70% of
patients had been initiated treatment at one month. Therefore there is a definite
need to improve the health systems in order to improve on these delays.
PMID- 25129691
TI - Women's age and embryo developmental speed accurately predict clinical pregnancy
after single vitrified-warmed blastocyst transfer.
AB - The aim of this study was to establish a simple, objective blastocyst grading
system using women's age and embryo developmental speed to predict clinical
pregnancy after single vitrified-warmed blastocyst transfer. A 6-year
retrospective cohort study was conducted in a private infertility centre. A total
of 7341 single vitrified-armed blastocyst transfer cycles were included, divided
into those carried out between 2006 and 2011 (6046 cycles) and 2012 (1295
cycles). Clinical pregnancy rate, ongoing pregnancy rate and delivery rates were
stratified by women's age (<35, 35-37, 38-39, 40-41, 42-45 years) and time to
blastocyst expansion (<120, 120-129, 130-139, 140-149, >149 h) as embryo
developmental speed. In all the age groups, clinical pregnancy rate, ongoing
pregnancy rate and delivery rates decreased as the embryo developmental speed
decreased (P < 0.0001). A simple five-grade score based on women's age and embryo
developmental speed was determined by actual clinical pregnancy rates observed in
the 2006-2011 cohort. Subsequently, the novel grading score was validated in the
2012 cohort (1295 cycles), finding an excellent association. In conclusion, we
established a novel blastocyst grading system using women's age and embryo
developmental speed as objective parameters.
PMID- 25129692
TI - Cryobanking of human ovarian tissue: Do women still want their tissue stored
beyond 5 years?
AB - Cryopreservation of ovarian tissue is one way of preserving fertility in young
women with a malignant disease or other disorders that require gonadotoxic
treatment. The purpose of the study was to explore how many women remained
interested in continued cryostorage of their ovarian tissue beyond an initial 5
year period. Between 1999 and 2006, a total of 201 girls and young women had one
ovary cryopreserved for fertility preservation in Denmark. One hundred of these
met our inclusion criteria, which included a follow-up period of at least 5
years, and were mailed a questionnaire. The response rate was 95%. Sixteen of the
patients (17%) stated that they wanted disposal of their tissue; the main reason
was completion of family (63%). The mean age of those requesting disposal was
36.6 years, whereas those still wanting their tissue stored were significantly
younger, with a mean age of 33.0 years (P < 0.008). In conclusion, most women
with ovarian tissue cryobanked requested continued cryostorage after an initial
period of at least 5 years. The main reason for requesting disposal was
successful completion of a family.
PMID- 25129690
TI - Targeted sequencing by proximity ligation for comprehensive variant detection and
local haplotyping.
AB - Despite developments in targeted gene sequencing and whole-genome analysis
techniques, the robust detection of all genetic variation, including structural
variants, in and around genes of interest and in an allele-specific manner
remains a challenge. Here we present targeted locus amplification (TLA), a
strategy to selectively amplify and sequence entire genes on the basis of the
crosslinking of physically proximal sequences. We show that, unlike other
targeted re-sequencing methods, TLA works without detailed prior locus
information, as one or a few primer pairs are sufficient for sequencing tens to
hundreds of kilobases of surrounding DNA. This enables robust detection of single
nucleotide variants, structural variants and gene fusions in clinically relevant
genes, including BRCA1 and BRCA2, and enables haplotyping. We show that TLA can
also be used to uncover insertion sites and sequences of integrated transgenes
and viruses. TLA therefore promises to be a useful method in genetic research and
diagnostics when comprehensive or allele-specific genetic information is needed.
PMID- 25129693
TI - The social context for surrogates' motivations and satisfaction.
AB - This Commentary takes up two of the main findings by Imrie and Jadva's study,
namely surrogates' satisfaction with the post-surrogacy contact with intended
parents and their motivation for surrogacy. It argues that the findings are in
keeping with other qualitative research on surrogacy and that this similarity is
not the result of the similarity of surrogates' psychological makeup. The
Commentary highlights the centrality of social meanings and definitions, and
following Howard Becker, insists on taking into account the collective doings
that inform and shape individual feelings and behaviour.
PMID- 25129695
TI - Bayesian Proteoform Modeling Improves Protein Quantification of Global Proteomic
Measurements.
AB - As the capability of mass spectrometry-based proteomics has matured, tens of
thousands of peptides can be measured simultaneously, which has the benefit of
offering a systems view of protein expression. However, a major challenge is that
with an increase in throughput, protein quantification estimation from the native
measured peptides has become a computational task. A limitation to existing
computationally-driven protein quantification methods is that most ignore protein
variation, such as alternate splicing of the RNA transcript and post
translational modifications or other possible proteoforms, which will affect a
significant fraction of the proteome. The consequence of this assumption is that
statistical inference at the protein level, and consequently downstream analyses,
such as network and pathway modeling, have only limited power for biomarker
discovery. Here, we describe a Bayesian model (BP-Quant) that uses statistically
derived peptides signatures to identify peptides that are outside the dominant
pattern, or the existence of multiple over-expressed patterns to improve relative
protein abundance estimates. It is a research-driven approach that utilizes the
objectives of the experiment, defined in the context of a standard statistical
hypothesis, to identify a set of peptides exhibiting similar statistical behavior
relating to a protein. This approach infers that changes in relative protein
abundance can be used as a surrogate for changes in function, without necessarily
taking into account the effect of differential post-translational modifications,
processing, or splicing in altering protein function. We verify the approach
using a dilution study from mouse plasma samples and demonstrate that BP-Quant
achieves similar accuracy as the current state-of-the-art methods at proteoform
identification with significantly better specificity. BP-Quant is available as a
MatLab (r) and R packages at https://github.com/PNNL-Comp-Mass-Spec/BP-Quant.
PMID- 25129696
TI - Multifunctional graphene quantum dots for simultaneous targeted cellular imaging
and drug delivery.
AB - This study demonstrates that ligand-modified graphene quantum dots (GQDs)
facilitate the simultaneous operation of multiple tasks without the need for
external dyes. These tasks include selective cell labeling, targeted drug
delivery, and real-time monitoring of cellular uptake. Folic acid (FA)-conjugated
GQDs are synthesized and utilized to load the antitumor drug doxorubicin (DOX).
The fabricated nanoassembly can unambiguously discriminate cancer cells from
normal cells and efficiently deliver the drug to targeted cells. The inherent
stable fluorescence of GQDs enables real-time monitoring of the cellular uptake
of the DOX-GQD-FA nanoassembly and the consequent release of drugs. The
nanoassembly is specifically internalized rapidly by HeLa cells via receptor
mediated endocytosis, whereas DOX release and accumulation are prolonged. In
vitro toxicity data suggest that the DOX-GQD-FA nanoassembly can target HeLa
cells differentially and efficiently while exhibiting significantly reduced
cytotoxicity to non-target cells.
PMID- 25129697
TI - Adsorption at the biocompatible alpha-pinene-water interface and emulsifying
properties of two eco-friendly surfactants.
AB - In this contribution, we provide an accurate characterization at the alpha
pinene/water interface of two commercial polyoxytheylene glycerol ester
surfactants which differ in the number of ethylene oxide (EO) groups, comprising
a systematic analysis of interfacial pressure isotherms, dynamic curves,
interfacial rheology and emulsifying properties. Polyoxyethylene glycerol esters
derived from cocoa oil are non-ionic surfactants obtained from a renewable source
which fulfill the environmental and toxicological requirements to be used as eco
friendly emulsifying agents. alpha-Pinene is a renewable biosolvent completely
insoluble in water, which could find numerous applications. Interfacial rheology
and equilibrium interfacial pressure data fitted a rigorous reorientation model
that assumes that the surfactant molecules, when adsorbed at the interface, can
acquire two orientations. The surfactant with the highest number of EO groups
(Levenol C201) turned out to be more surface active at the alpha-pinene/water
interface. In addition, the surfactant with the lowest number of EO groups
(Levenol H&B) is solubilized into the adjacent oil phase. Slightly concentrated
alpha-pinene emulsions were obtained using both surfactants. Nevertheless, more
stable alpha-pinene emulsions with smaller droplet sizes and lower polidispersity
were obtained when Levenol C201 was used as emulsifier instead of Levenol H&B.
The systematic characterization presented in this work provides important new
findings on the interfacial and emulsifying properties of polyoxytheylene
glycerol ester surfactants, which can be applied in the rational development of
new biocompatible products.
PMID- 25129698
TI - Exercise-based injury prevention in child and adolescent sport: a systematic
review and meta-analysis.
AB - BACKGROUND: The promotion of sport and physical activity (PA) for children is
widely recommended to support a healthy lifestyle, but being engaged in sport
bears the risk of sustaining injuries. Injuries, in turn, can lead to a reduction
in current and future involvement in PA and, therefore, may negatively affect
future health as well as quality of life. Thus, sports injury prevention is of
particular importance in youth. OBJECTIVE: The aim of this systematic review was
to quantify the effectiveness of exercise-based injury prevention programs in
child and adolescent sport in general, and with respect to different
characteristics of the target group, injury prevention program, and outcome
variables. DATA SOURCES: An Internet-based literature search was conducted in six
databases (CINAHL, Cochrane, EMBASE, ISI Web of Science, PubMed, SPORTDiscus)
using the following search terms with Boolean conjunction: (sport injur* OR
athletic injur* OR sport accident*) AND (prevent* OR prophylaxis OR avoidance)
AND (child* OR adolescent OR youth). STUDY SELECTION: Randomized controlled
trials and controlled intervention studies in organized sport, published in
English in a peer-reviewed journal, analyzing the effects of an exercise-based
injury prevention program in athletes younger than 19 years of age. DATA
EXTRACTION: Two reviewers evaluated eligibility and methodological quality. Main
outcome extracted was the rate ratio (RR). Statistical analyses were conducted
using the inverse-variance random effects model. RESULTS: Twenty-one trials,
conducted on a total of 27,561 athletes (median age 16.7 years [range 10.7
17.8]), were included. The overall RR was 0.54 (95% CI 0.45-0.67) [p < 0.001].
Girls profited more from injury prevention than boys (p = 0.05). Both prevention
programs with a focus on specific injuries (RR 0.48 [95% CI 0.37-0.63]) and those
aiming at all injuries (RR 0.62 [95% CI 0.48-0.81]) showed significant reduction
effects. Pre-season and in-season interventions were similarly beneficial (p =
0.93). Studies on programs that include jumping/plyometric exercises showed a
significant better (p = 0.002) injury preventive effect (RR 0.45 [95% CI 0.35
0.57], Z = 6.35, p < 0.001) than studies without such exercises (RR 0.74 [95% CI
0.61-0.90], Z = 3.03, p = 0.002). CONCLUSIONS: The results provide good evidence
and clearly demonstrate beneficial effects of exercise-based injury prevention
programs in youth sports as they can result in statistically significant and
practically relevant injury reduction. In particular, multimodal programs
including jumping/plyometric exercises can be recommended. However, there is a
considerable lack of data for children (under 14 years of age) and for individual
sports in general. Future research should include these groups and focus on the
effect of specific exercises and compliance.
PMID- 25129699
TI - The impact of exercise-induced bronchoconstriction on athletic performance: a
systematic review.
AB - BACKGROUND: Exercise-induced bronchoconstriction (EIB) describes the phenomenon
of transient airway narrowing in association with physical activity. Although it
may seem likely that EIB would have a detrimental impact on athletic performance,
this has yet to be established. OBJECTIVES: The aim of this review is to provide
a systematic appraisal of the current status of knowledge regarding EIB and
exercise performance and to highlight potential mechanisms by which performance
may be compromised by EIB. DATA SOURCES AND STUDY SELECTION: PubMed/Medline and
EBSCO databases were searched up to May 2014 using the search parameter:
[('exercise' OR 'athlete') AND ('asthma' OR 'bronchoconstriction' OR
'hypersensitivity') AND 'performance']. This search string returned 243
citations. After systematically reviewing all of the abstracts, 101 duplicate
papers were removed, with 132 papers excluded for not including an exercise
performance outcome measure. RESULTS: The remaining ten studies that met the
initial criteria were included in this review; six evaluated the performance of
physically active individuals with asthma and/or EIB while four assessed the
effects of medication on performance in a comparable population. CONCLUSION: The
evidence concludes that whilst it is reasonable to suspect that EIB does impact
athletic performance, there is currently insufficient evidence to provide a
definitive answer.
PMID- 25129700
TI - Antibacterial phototoxic effects of synthetic asymmetric and glycosylated
curcuminoids in aqueous formulations: studies on curcumin and curcuminoids. LIV.
AB - The aim of this study was to evaluate the in vitro phototoxic potential of
synthetic asymmetric and glycosylated curcuminoids on planktonic model bacteria
by counting the colony forming units. The Gram-positive Enterococcus faecalis and
the Gram-negative Escherichia coli were exposed to aqueous solutions of the
curcuminoids (?2.5 MUM) in the presence or absence of selected pharmaceutical
excipients (Pluronic F127, PEG 400 and HPgammaCD) in combination with a low
irradiation dose (5 J/cm(2); lambdamax: 450 nm) of constant irradiance and time.
All the asymmetric curcuminoids, but only one of the glycosylated curcuminoids
demonstrated substantial phototoxic effect on E.faecalis (?4.7 log reduction).
Only two of the asymmetric curcuminoids showed a moderate to low phototoxic
effect on the more persistent E.coli. This study emphasized that aromatic
hydroxyl substituents in the para-position are important to maintain the
phototoxic potential of curcuminoids independent of molecular symmetry.
Glycosylation of the aromatic substituents resulted in a substantial loss in
phototoxicity towards planktonic bacteria, an apparent change in the non
radiative S1-decay process and a weaker interaction with Pluronic F127 compared
to the non-glycosylated curcuminoids. The selected excipients Pluronic F127, PEG
400 and HPgammaCD strongly influenced the phototoxic potential of the
unsymmetrical, non-glycosylated compounds.
PMID- 25129701
TI - A simple and effective method to synthesize fluorescent nanoparticles using
tryptophan and light and their lethal effect against bacteria.
AB - A simple, environmentally friendly and cost-effective method was used to
synthesize silver nanoparticles using tryptophan and light. To prepare the
nanoparticles, the following components were used: deionized water, silver
nitrate, light and tryptophan. The effects of the tryptophan concentration and
light exposure time on the formation of tryptophan silver nanoparticles (Tnnps)
were studied. The synthesized Tnnps were characterized using transmission
electron microscopy (TEM), absorption and fluorescence spectroscopy and zeta
potential measurements. The synthesized Tnnps were nearly spherical, with sizes
of approximately 17 nm. In addition, the antibacterial activity of Tnnps was
determined by monitoring the growth curves of strains of Escherichia coli,
Pseudomonas aeruginosa, Staphylococcus epidermidis, Serratia marcescens, and
Enterococcus faecalis using the microdilution test. The Minimum Inhibitory
Concentration (MIC) for 4 of 5 tested bacteria was determined to be between 20.0
and 17.5 MUg/mL for 48 h and between 22.5 and 20.0 MUg/mL for 72 h.
PMID- 25129703
TI - A calculator for temporal artery biopsy result prediction in giant cell arteritis
suspects.
PMID- 25129702
TI - High tibial osteotomy.
AB - High tibial osteotomy (HTO) is a widely accepted and performed procedure to treat
medial knee arthrosis. The aim of this review is to evaluate the different
surgical options in medial knee arthrosis, focusing on indications, patient's
selection, long-term follow-up and survival analysis of HTO. Comparison and
pooling of results are challenging because of different evaluation systems, small
cohort number, and different surgical techniques. No differences have been
described between opening and closing wedged HTO in terms of outcomes. Excellent
early survivorship and good clinical outcomes were reported also with concomitant
procedures. Correct indications, preoperative workup/planning, and technique
selection are essential in achieving good results. The choice between opening and
closing wedge osteotomy, graft selection in opening wedge HTO, comparison between
HTO and unicompartmental knee arthroplasty, and the results of revised HTO to
total knee replacement are currently under debate and will be discussed in the
present review.
PMID- 25129704
TI - Adjacent segment disease after anterior cervical interbody fusion: a multicenter
retrospective study of 288 patients with long-term follow-up.
AB - INTRODUCTION: Cervical discectomy with interbody fusion is a common procedure in
spinal surgery. The resultant biomechanical alterations accelerate degeneration
of the adjacent segment, but the contribution of natural degeneration to adjacent
segment disease is unclear. OBJECTIVE: To assess the long-term rate of surgery to
discs adjacent to cervical interbody fusion; and to assess the associated
incidence of cervico-brachial neuralgia and radiological degeneration of adjacent
discs. MATERIAL AND METHOD: A multicenter retrospective study included anterior
cervical discectomy patients at a minimum of 10 years' follow-up. Clinical
variables comprised pain, use of analgesics and surgical revision. Functional
assessment was performed on the Neck Disability Index (NDI). Radiologic
degeneration was assessed on the Goffin score based on cervical spine X-ray.
RESULTS: Two hundred and eighty-eight patients were contacted and filled out the
clinical questionnaire. Among the patients, 153 underwent radiological
reassessment. Mean age was 46 years (range, 16-73 years). Mean follow-up was 14.5
years (12-18 years). The rate of surgical revision on a disc adjacent to the
primary level was 5.9%. Frequent attacks of cervico-brachial neuralgia were
reported in 20.5% of cases. Radiologic adjacent segment degeneration was found in
81.3% of cases over follow-up. There was a significant correlation between degree
of radiologic adjacent segment degeneration and NDI (P=0.02). DISCUSSION:
Degeneration adjacent to discectomy/fusion is partly due to aging. The present
findings, however, agree with the literature and indicate accelerated
degeneration in adjacent segments. These findings should be taken into account in
treatment decision-making and suggest a possible interest of more physiological
surgery such as arthroplasty. LEVEL OF EVIDENCE: IV - Multicenter retrospective
study.
PMID- 25129705
TI - The reliability of the anterior pelvic plane for computer navigated acetabular
component placement during total hip arthroplasty: prospective study with the EOS
imaging system.
AB - INTRODUCTION: Computer navigated total hip arthroplasty is mostly based on the
use of the anterior pelvic plane (APP) as a reference. EOS is a new imaging
system that provides three-dimensional analysis of the pelvis in a functional
position with a low dose of radiation. The aim of this study was to evaluate the
reliability of the APP for placement of the cup during computer navigated THA
using EOS. HYPOTHESIS: The reliability of the APP is limited for the placement of
the acetabular cup during computer navigated THA. MATERIALS AND METHODS: This was
a prospective monocentric study using the EOS imaging system evaluating 44
patients in the standing position three months after computer navigated THA
(Orthopilot). Reproducibility of EOS measurements were analyzed using SterEOS
software and the reliability of the navigation data for the position of the cup
were assessed. RESULTS: Intra and interobserver reproducibility of the
measurements of the orientation of the cup by EOS were good with correlation
coefficients above 93% and 95% and confidence intervals of less than +/-5 degrees
. Mean cup inclination and anteversion were 41.3 degrees and 20.9 degrees and
44.3 degrees and 29.5 degrees respectively in operatively and post-operatively.
The differences between measurements of operative cup inclination using computer
assisted navigation and the post-operative EOS measurements were significant
(P<0.05) with a correlation coefficient of less than 40%. DISCUSSION: Our study
confirms the lack of precision of the APP as a reference for positioning of the
acetabular component, especially in relation to anteversion. Although for many
years the APP was considered to be a global reference, in fact, it is subject to
significant inter-individual variations and variations during changes in
position. These factors, associated with the difficulty of determining the
preoperative APP, explain the lack of reliability of this reference. Preoperative
evaluation of the orientation of APP by EOS and its integration into the
navigation system could help the operator position these components. LEVEL OF
EVIDENCE: Level III Prospective diagnostic case controlled study.
PMID- 25129706
TI - Blade-plate fixation for distal femoral fractures: a case-control study.
AB - BACKGROUND: The blade-plate is the earliest of the contemporary internal fixation
devices introduced for distal femoral fractures. The recent development of
dedicated, fixation devices has considerably limited its use. The objective of
this study was to evaluate outcomes after blade-plate fixation and after fixation
using other devices. HYPOTHESIS: Outcomes after blade-plate fixation are similar
to those after condylar screw-plate, distal femoral nail, or locking condylar
plate fixation. MATERIAL AND METHODS: We reviewed outcomes after 62 patients
managed with blade-plate fixation and included in a multicentre retrospective
study (n=57) or a multicentre prospective study (n=5) and we compared them to
outcomes after fixation using condylar screw-plates (n=82), distal femoral nail
(n=219), or locking condylar plates (n=301). The four groups were comparable for
age, gender distribution, occupational status, prevalence of skin wounds, patient
related factors, type of accident, and type of fracture. The evaluation relied on
the clinical International Knee Society (IKS) score and on radiographs. RESULTS:
No significant differences existed across the four groups for operative time,
blood transfusion use, complications, need for bone grafting, non-union rate, or
IKS score values. The early surgical revision rate for removal of the fixation
material was 4% with the blade-plate and 16% with the other three fixation
devices (P=0.02). Post-operative fracture deformity was similar in the four
groups with, however, a higher proportion of residual malalignment in the screw
fixation group. The final anatomic axis was 3.3+/-1.4 degrees with the blade
plate versus 2.3+/-3.7 degrees with the other three fixation devices. The blade
plate group had few patients with axial malalignment, and the degree of
malalignment was limited to 3 degrees of varus and 10 degrees of valgus at the
most, compared to 10 degrees and 18 degrees respectively, with the other three
fixation devices. CONCLUSION: Despite the now extremely limited use and teaching
of blade-plate fixation, as well as the undeniable technical challenges raised by
the implantation of this device, the blade-plate is a simple, strong, and
inexpensive fixation method. It remains reliable for the fixation of distal
femoral fractures. The disfavour into which the blade-plate is currently falling
is not warranted. LEVEL OF EVIDENCE: III, case-control study.
PMID- 25129707
TI - Application of electrochemical technology for removing petroleum hydrocarbons
from produced water using lead dioxide and boron-doped diamond electrodes.
AB - Although diverse methods exist for treating polluted water, the most promising
and innovating technology is the electrochemical remediation process. This paper
presents the anodic oxidation of real produced water (PW), generated by the
petroleum exploration of the Petrobras plant-Tunisia. Experiments were conducted
at different current densities (30, 50 and 100 mA cm(-2)) using the lead dioxide
supported on tantalum (Ta/PbO2) and boron-doped diamond (BDD) anodes in an
electrolytic batch cell. The electrolytic process was monitored by the chemical
oxygen demand (COD) and the residual total petroleum hydrocarbon [TPH] in order
to know the feasibility of electrochemical treatment. The characterization and
quantification of petroleum wastewater components were performed by gas
chromatography mass spectrometry. The COD removal was approximately 85% and 96%
using PbO2 and BDD reached after 11 and 7h, respectively. Compared with PbO2, the
BDD anode showed a better performance to remove petroleum hydrocarbons compounds
from produced water. It provided a higher oxidation rate and it consumed lower
energy. However, the energy consumption and process time make useless anodic
oxidation for the complete elimination of pollutants from PW. Cytotoxicity has
shown that electrochemical oxidation using BDD could be efficiently used to
reduce more than 90% of hydrocarbons compounds. All results suggest that
electrochemical oxidation could be an effective approach to treat highly
concentrated organic pollutants present in the industrial petrochemical
wastewater and significantly reduce the cost and time of treatment.
PMID- 25129708
TI - Effects of dietary wheat bran arabinoxylans on cholesterol metabolism of
hypercholesterolemic hamsters.
AB - The aim of the present study is to investigate the effects of dietary wheat bran
arabinoxylans (AXs) on cholesterol metabolism in hypercholesterolemic hamsters.
The hamsters were divided into 3 groups and fed the experimental diets containing
AXs or oat beta-glucan at a dose of 5 g/kg for 30 days. As the results, the AXs
lowered plasma total cholesterol and LDL-cholesterol concentrations, and
increased excretions of total lipids, cholesterol and bile acids, as well as oat
beta-glucan. The AXs reduced the activity of 3-hydroxy-3-methyl glutaryl-coenzyme
A (HMG-CoA) reductase, and increased the activity of cholesterol 7-alpha
hydroxylase (CYP7A1) in liver. Moreover, the AXs increased propionate and the
total short-chain fatty acids (SCFAs) concentrations. These results indicated
that dietary AXs reduced the plasma total cholesterol and LDL-cholesterol
concentrations by promoting the excretion of fecal lipids, regulating the
activities of HMG-CoA reductase and CYP7A1, and increasing colonic SCFAs in
hamsters.
PMID- 25129709
TI - A novel method to estimate the stiffness of carbohydrate polyelectrolyte polymers
based on the ionic strength dependence of zeta potential.
AB - Polysaccharides have received a great deal of attention from, for example, the
food, cosmetic and pharmaceutical industries. Their conformations
(flexibility/stiffness) span a wide range of conformational flexibilities with
large hydrated volumes, these properties are important in relation to
polysaccharide structure-function relationships. Perhaps the simplest parameter
available to estimate the dilute solution conformation of polysaccharides is the
Smidsrod-Haug stiffness parameter (B) where the stiffness of polyelectrolytes can
be estimated by measuring the intrinsic viscosity at a number of different ionic
strengths. In this paper we propose an alternative method for estimating the
Smidsrod-Haug stiffness parameter (B) using the ionic strength dependency of zeta
potential. For this purpose we have studied a number of different
polysaccharides.
PMID- 25129710
TI - Synergistic effects of mixed salt on the gelation of kappa-carrageenan.
AB - The effect of the addition of calcium or sodium ions on the potassium induced
gelation of kappa-carrageenan (kappa-car) is investigated using oscillatory shear
rheology and turbidimetry. Both the gelation kinetics and the steady state shear
moduli are investigated. Gelation in mixed salt solutions is compared with that
in pure potassium and calcium solutions. It is shown that the elastic shear
modulus increases with increasing pure KCl concentration, but decreases with
increasing pure CaCl2 concentration. In mixed salts, gelation of kappa-car is
induced by potassium and addition of CaCl2 leads to an increase of the elastic
modulus with increasing CaCl2 concentration. kappa-Car gelled at low mixed salt
concentrations for which it remained liquid in pure salt. At equivalent ionic
strengths, the effect of adding NaCl on potassium induced gelation is much
weaker. In pure KCl solutions, kappa-car gels are transparent, but in pure CaCl2
they become increasingly turbid with increasing CaCl2 concentration. The
turbidity of gels formed in mixed salts is intermediate.
PMID- 25129711
TI - The excreted polysaccharide of Pleurotus eryngii inhibits the foam-cell formation
via down-regulation of CD36.
AB - Previous study has verified the polysaccharide from the fruiting body of
Pleurotus eryngii (PEPE) is capable of decreasing the lipid content in both of
cell-line and mouse model. However, little is known about underlying mechanisms
and whether this bioactive polysaccharide exists in submerged culture. Here, we
verified the excreted polysaccharides EP and EP-1 from submersion culture of P.
eryngii have the remarkable inhibitory effects on lipid accumulation in
macrophage-derived foam cells. Structure analysis indicates EP-1 consists of D
types of glucose, galactose and mannose with the main beta(1 -> 3)-glucan
glycosidic linkage branched at O-6 by alpha-D-glucose while EP digested by beta
1,3-glucanase fails to decrease the lipid accumulation, suggesting that the
special structure is essential for its function. Expression analysis suggests
that EP is able to cause the down-regulation of the scavenger receptor-CD36 on
both transcription and protein levels. Most importantly, EP can be obtained by
fermentation in a mass-production.
PMID- 25129712
TI - Thermo-mechanical and hydrophilic properties of polysaccharide/gluten-based
bioplastics.
AB - The influence of adding different polysaccharides (locust bean gum, LBG; methyl
cellulose, MC; and carboxymethyl cellulose, CMC) to gluten-based biodegradable
polymeric materials was assessed in this work. Gluten/polysaccharide/plasticiser
bioplastics were prepared at different polysaccharide concentrations (0-4.5%) and
pH values by mixing in a two-blade counter-rotating batch mixer (at 25 degrees C
under adiabatic conditions) and thermomoulding at 9MPa and 130 degrees C.
Bioplastic probes were evaluated through dynamic mechanical thermal analysis,
tensile strength and water absorption capacity tests. Results pointed out that a
moderate enhancement of the network structure may be achieved by adding
polysaccharide at a pH close to the protein isoelectric point (pH 6), which also
conferred a further thermosetting capacity to the system. Moreover, the addition
of MC and CMC was found to significantly enhance material elongation properties.
However, the presence of charges induced by pH leaded to a higher incompatibility
between the polysaccharide and protein domains forming the composite. The pH
value played a relevant role in the material water absorption, which
significantly increased under acidic or basic conditions (particularly at pH 3).
PMID- 25129713
TI - Modification of carboxymethyl cellulose grafted with collagen peptide and its
antioxidant activity.
AB - Carboxymethyl cellulose used in wounds has little antioxidant capacity. The aim
of the present study was to improve the scavenging ability of carboxymethyl
cellulose by modified with collagen peptide. The reaction conditions have been
optimized by varying mass ratio of collagen peptide to carboxymethyl cellulose,
temperature and reaction time. Antioxidant activities of carboxymethyl cellulose
derivatives (CMCC) were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH),
hydroxyl, superoxide radicals and the reducing power. The effects of
concentration, degree of substitution (DS) and molecular weight on three
different radicals scavenging activity and reducing power were examined.
Methylthiazol tetrazolium (MTT) assay was used to evaluate the fibroblasts cells
cytotoxicity of CMCC. Results showed that the scavenging effects of CMCC
increased with the increasing of DS and concentration. This product of CMCC
possesses a distinct antioxidant capacity on radicals.
PMID- 25129714
TI - Synthesis and surface modification of polyurethanes with chitosan for
antibacterial properties.
AB - Surface modification and providing antibacterial properties to the materials or
devices are getting great attention especially in the last decades. In this
study, polyurethane (PU) films were prepared by synthesizing them in medical
purity from toluene diisocyanate and polypropylene ethylene glycol without using
any other ingredients and then the film surfaces were modified by covalent
immobilization of chitosan (CH) which has antibacterial activity. CH immobilized
PU films (PU-CH) were found to be more hydrophilic than control PU films.
Electron Spectroscopy for Chemical Analysis (ESCA) and Atomic Force Microscopy
(AFM) analyses showed higher nitrogen contents and rougher surface topography for
PU-CH compared to PU films. Modification with CH significantly increased
antibacterial activity against Gram positive (Staphylococcus aureus) and Gram
negative (Pseudomonas aeruginosa) bacteria. It was observed that the number of
bacteria colonies were less about 10(2)-10(5) CFU/mL and number of attached
viable bacteria decreased significantly after CH modification of PU films.
PMID- 25129715
TI - Transglycosylation reactions between galactomannans and arabinogalactans during
dry thermal treatment.
AB - Aiming to investigate the possible occurrence of transglycosylation reactions
between galactomannans and side chains of arabinogalactans during coffee
roasting, mixtures of beta-(1 -> 4)-D-mannotriose and alpha-(1 -> 5)-L
arabinotriose were subjected to dry thermal treatments at 200 degrees C. Matrix
assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis
allowed identifying polysaccharides composed by pentose and hexose residues with
a degree of polymerization up to 18 residues. Methylation analysis showed the
occurrence of new types of glycosidic linkages in all thermally treated mixtures,
as well as the occurrence of terminally and 5-linked ribose, possibly formed from
arabinose isomerization. Also, xylose and lyxose were identified and proposed to
be formed from mannose. These results support the occurrence of
transglycosylation reactions promoted by roasting involving both oligosaccharides
in the starting mixtures, resulting in arabinan and mannan chimeric
polysaccharides. These structural features were also found in roasted coffee
polysaccharide samples.
PMID- 25129716
TI - Xylan-cellulose films: improvement of hydrophobicity, thermal and mechanical
properties.
AB - Xylan-rich hemicellulose from corn cob has been used for new material
elaboration. Commercial cellulose was used as reinforcement in different
percentages to improve properties of the films. Two types of composites were
elaborated by solvent casting. Hydrophilic films, composed by bleached
hemicellulose (BH), unmodified cellulose and glycerol as plasticizer, and
hydrophobic films formed by acetylated bleached hemicellulose (BAH) and
acetylated cellulose. The degree of substitution of BAH was 1.8 and acetylated
cellulose presented a degree of substitution of 0.54. Thermal and mechanical
properties of films were analyzed. A significant improvement was observed in the
thermal behavior of hydrophobic films (Tmax ~ 368 degrees C) respect to
hydrophilic films (Tmax ~ 300 degrees C). Although the addition of cellulose
clearly increase the properties of both type of films, hydrophobic films (Young's
modulus ~ 2300 MPa, strength ~ 44.1MPa, strain at break ~ 5.7%) showed better
mechanical properties than hydrophilic films (Young's modulus ~ 3 MPa, strength ~
3.3 MPa, strain at break ~ 5.3%).
PMID- 25129717
TI - Purification, characterization and immunomodulatory effects of Plantago depressa
polysaccharides.
AB - Four purified polysaccharide fractions from seeds of Plantago depressa (PDSP-1,
PDSP-2, PDSP-3 and PDSP-4) were obtained by isolation and purification using DEAE
52 cellulose and Sephacryl S-400 HR chromatography. Basic physicochemical
properties including molecular weight, chemical composition, FT-IR and glycosidic
linkage of these fractions were investigated. They seemed to be homogeneous
acidic protein-bound heteropolysaccharides with high molecular weight of over
1000 kDa and contained a lot more beta-type glycosidic linkages than alpha-type.
PDSP-3 mainly contained mannose, arabinose and fucose, and the others were rich
in arabinose, fucose and galacturonic acid. The immunomodulatory effects of them
were assessed by splenocyte proliferation index and production of NO and TNF
alpha from macrophages. They all showed significant immunomodulatory activities,
and PDSP-3 presented the strongest effect. Their observed differences in
biological activities were probably due to their structure differences. And
monosaccharide compositions, linkage types and molecular weight may affect their
immunomodulatory activities.
PMID- 25129718
TI - (1 -> 3)-beta-D-Glucan nanofibers from paramylon via electrospinning.
AB - (1 -> 3)-beta-D-Glucans of paramylon from Euglena gracilis were dissolved in
concentrated formic acid and electrospinning was conducted using a newly designed
setup. The diameter of the as-spun fibers ranged from 0.05 to 1 MUm, and most of
the fibers were straight and aligned parallel to two arbitrary fins (electrodes).
By polarized optical microscopy, we determined that the anisotropic texture of
the fibers was indicative of parallel alignment of the molecular chains to the
fiber axis. The wide-angle X-ray scattering curve for the fibers showed amorphous
halo scattering in spite of the high crystallinity of starting paramylon powder.
PMID- 25129719
TI - Physicochemical characteristics of polysaccharide conjugates prepared from fresh
tea leaves and their improving impaired glucose tolerance.
AB - Hot-water extracts were prepared from fresh tea leaves and fractionated by DEAE
cellulose DE-52 column chromatography to yield one unexplored polysaccharide
conjugate fraction TPC-L (tea polysaccharide conjugates). Chemical components,
molecular weight and its distribution, water vapor sorption properties, zeta
potentials and optical characteristics of TPC-L were investigated. As compared
with injured cell group, the two dosages of TPC-L (150 and 300 MUg/mL) were
discovered to possess remarkably protective effect on human umbilical vein
endothelial cells against impairments induced by high glucose in a dose-dependent
manner (p < 0.05, p < 0.001, respectively). Compared with group NC (normal
control), the ingestion of 40 mg/kg of TPC-L could significantly reduce blood
glucose levels of normal mice ingesting starch, and significant difference of AUC
(area under the curve of blood glucose) and DeltaAUC (p < 0.05, p < 0.01) at the
postprandial time point of 0.5 and 1.0 h were observed. The three dosages of TPC
L (10, 40 and 160 mg/kg) did not significantly lower postprandial blood glucose
levels of normal mice ingesting glucose. TPC-L could improve starch tolerance to
prevent impaired glucose tolerance (IGT) from developing into diabetes as well as
protective effects on HUVE cells against impairments induced by high glucose It
was suggested that TPC-L improved IGT through its capability of inhibition on
digestive enzymes.
PMID- 25129720
TI - Structures of octenylsuccinylated starches: effects on emulsions containing beta
carotene.
AB - Starches with different amylopectin contents and different molecular sizes
prepared using acid hydrolysis were hydrophobically modified using
octenylsuccinic anhydride (OSA). The OSA-modified starches were used as
surfactants to stabilize emulsions of beta-carotene and canola oil dispersed in
water. The objective of this study is to investigate the relationship between
starch molecular structure and the chemical stability of the emulsified beta
carotene, as well as the colloidal stability of emulsion droplets during storage.
The oil droplet size in emulsions was smaller when starch had (a) lower
hydrodynamic volume (Vh) and (b) higher amylopectin content. The oxidative
stability of beta-carotene was similar across samples, with higher results at
increased amylopectin content but higher Vh. Steric hindrance to coalescence
provided by adsorbed OSA-modified starches appears to be improved by more rigid
molecules of higher degree of branching.
PMID- 25129721
TI - Assessment of the physical, mechanical, and moisture-retention properties of
pullulan-based ternary co-blended films.
AB - Multi-component substances made through direct blending or blending with co
drying can form films on the surfaces of intermediate moisture foods (IMFs),
which help retain moisture and protect food texture and flavor. An IMF film
system based on pullulan, with glycerol serving as the plasticizer, was studied
using alginate and four different types of polysaccharides (propyleneglycol
alginate, pectin, carrageenan, and aloe polysaccharide) as the blend-modified
substances. The physical, mechanical, color, transparency, and moisture-retention
properties of the co-blended films with the polysaccharides were assessed. A new
formula was established for the average moisture retention property, water
barrier, tensile strength, elongation at break, and oxygen barrier property of
the ternary co-blended films using the Design Expert software. The new model
established for moisture content measurement used an indirect method of film
formation on food surfaces by humectants, which should expedite model validation
and allow a better comprehension of moisture transfer through edible films.
PMID- 25129722
TI - CTAB turbidimetric method for assaying hyaluronic acid in complex environments
and under cross-linked form.
AB - The cetyltrimethylammonium bromide turbidimetric method (CTM) has been developed
to quantify the hyaluronic acid (HA) in complex media to overcome the lack of
selectivity and specificity of the standard carbazole method. The objective of
this work is to assess the potential application of CTM to determine HA
concentration. Factors such as duration of incubation, linearity range, HA size
and form (natural linear HA or cross linked HA), pH and ionic environment impact
were investigated. The incubation time was set to 10 min and the calibration
curve was linear up to 0.6 g L(-1). The quantitative method was relevant whatever
the HA size and form, and also for a wide range of conditions. The robustness of
the CTM added to its high specificity and simplicity demonstrated that the CTM is
a valuable method that would be an interesting substitute to the carbazole assay
for HA quantification.
PMID- 25129723
TI - Immunomodulation of human macrophages and myeloid cells by 2-substituted (1-3)
beta-D-glucan from P. parvulus 2.6.
AB - beta-glucans produced by eukaryotic cells and by microorganisms are known to
modulate immune responses by affecting macrophage activation. Here, we have
investigated the effect of purified 2-substituted (1-3)-beta-D-glucan, produced
by either Pediococcus parvulus 2.6 or Lactococcus lactis NZ9000[pNGTF], on the
effector functions of human PMA-differentiated THP-1 cells and M1 pro
inflammatory monocyte-derived macrophages. The results reveal that this kind of
beta-D-glucan activates macrophages and has an anti-inflammatory effect.
PMID- 25129724
TI - Antioxidant and immunological activities of polysaccharides from Gentiana scabra
Bunge roots.
AB - Two polysaccharide fractions, GSP I-a and GSP II-b, were isolated from Gentiana
scabra Bunge roots. Both GSP I-a and GSP II-b comprised seven monosaccharides:
fructose, mannose, rhamnose, galacturonic acid, glucose, galactose, and fucose.
Ultraviolet and infrared analyses show that GSP I-a and GSP II-b are
proteoglycans. In vitro evaluation of the antioxidant activity suggests that GSP
I-a and GSP II-b scavenge 1,1-diphenyl-2-picrylhydrazyl radicals. However, the
scavenging activity of the latter is stronger than that of the former. GSP I-a
and GSP II-b have relatively low reducing powers and scavenging activities toward
superoxide anions and hydroxyls. GSP I-a and GSP II-b significantly increase
lymphocyte proliferation when lipopolysaccharide is used as a mitogen for
lymphocytes, but only GSP I-a can significantly increase lymphocyte proliferation
within the test-dosage range when concanavalin A is used as a mitogen.
PMID- 25129725
TI - Surface-initiated atom transfer radical polymerization from chitin nanofiber
macroinitiator film.
AB - This paper reports the preparation of chitin nanofiber-graft-poly(2-hydroxyethyl
acrylate) (CNF-g-polyHEA) films by surface-initiated atom transfer radical
polymerization (ATRP) of HEA monomer from a CNF macroinitiator film. First, a CNF
film was prepared by regeneration from a chitin ion gel with an ionic liquid.
Then, acylation of the CNF surface with alpha-bromoisobutyryl bromide was carried
out to obtain the CNF macroinitiator film having the initiating moieties (alpha
bromoisobutyrate group). The surface-initiated graft polymerization of HEA from
the CNF macroinitiator film by ATRP was performed to produce the CNF-g-polyHEA
film. The IR, XRD, and SEM measurements of the resulting film indicated the
progress of the graft polymerization of HEA on surface of CNFs. The molecular
weights of the grafted polyHEAs increased with prolonged polymerization times,
which affected the mechanical properties of the films under tensile mode.
PMID- 25129726
TI - True molecular solutions of natural cellulose in the binary ionic liquid
containing solvent mixtures.
AB - Evidence is presented for the first time of true molecular dissolution of
cellulose in binary mixtures of common polar organic solvents with ionic liquid.
Cryogenic transmission electron microscopy, small-angle neutron-, X-ray- and
static light scattering were used to investigate the structure of cellulose
solutions in mixture of dimethyl formamide and 1-ethyl-3-methylimidazolium
acetate. Structural information on the dissolved chains (average molecular weight
~ 5 * 10(4)g/mol; gyration radius ~ 36 nm, persistence length ~ 4.5 nm), indicate
the absence of significant aggregation of the dissolved chains and the calculated
value of the second virial coefficient ~ 2.45 * 10(-2)mol ml/g(2) indicates that
this solvent system is a good solvent for cellulose. More facile dissolution of
cellulose could be achieved in solvent mixtures that exhibit the highest
electrical conductivity. Highly concentrated cellulose solution in pure ionic
liquid (27 wt.%) prepared according to novel method, utilizing the rapid
evaporation of a volatile co-solvent in binary solvent mixtures at superheated
conditions, shows insignificant cellulose molecular aggregation.
PMID- 25129727
TI - Radiolytically depolymerized sodium alginate improves physiological activities,
yield attributes and composition of essential oil of Eucalyptus citriodora Hook.
AB - Eucalyptus citriodora Hook. is highly valued for its citronellal-rich essential
oil (EO) extracted from its leaves. Hence, escalated EO production of eucalyptus
is the need of hour. Marine polysaccharides (sodium alginate) are processed
through gamma radiation of particular intensity, to obtain the irradiated sodium
alginate (ISA). A pot experiment was conducted to study the effect of foliar
application of ISA on growth, biochemical, physiological, EO yield and
composition of E. citriodora. The treatments were applied as: foliar spray of
deionized water only (control), seed soaked with ISA (90 mg L(-1)) and foliar
spray of ISA with 30, 60, 120 and 240 mg L(-1). The treatment 6 (spray of ISA at
120 mg L(-1)) showed the highest value for most of the parameters studied. It
also enhanced the EO content (33.3%), EO yield (86.7%), citronellal content
(63.4%) and citronellal yield (205.5%) as compared to the control.
PMID- 25129728
TI - From algal polysaccharides to cyclodextrins to stabilize a urease inhibitor.
AB - N-Butyl-phosphorotriamide (NBPT) is a fertilizer widely used for its urease
inhibiting properties. Nevertheless, formulations currently commercialized are
complex and do not avoid severe decrease of activity due to the low stability of
the bioactive compound under acidic conditions. According to its structure, NPBT
was thought to be able to interact with both polar additives, by its
phosphoramide function, and hydrophobic ones, through its alkyl chain. In this
context, and in order to simplify formulations of this bioactive compound, a
panel of natural polysaccharides was studied, including starch, beta-(1,3)
glucans, carraghenans and alginates. We also used cyclodextrins, characterized
the most stable inclusion complex with alpha-cyclodextrin and evaluated the
stability of NBPT thus protected against hydrolysis under acidic conditions.
PMID- 25129729
TI - Effects of chitosan on oxidative stress and related factors in hemodialysis
patients.
AB - In recent world-wide studies, chitosans were tested as a dietary supplement for
inhibiting the absorption of certain lipids and bile acids. We previously
demonstrated the antioxidative and renoprotective potential of chitosan
supplementation in chronic renal failure using 5/6 nephrectomized rats. In this
study, we report the effects of chitosan on oxidative stress and related factors
in hemodialysis patients. The ingestion of chitosan over a 12-week period
resulted in a significant decrease in serum indoxyl sulfate and phosphate levels,
compared with the levels prior to the start of the study. The ingestion of
chitosan also resulted in a lowered ratio of oxidized to reduced albumin and a
decrease in the level of advanced oxidized protein products. In in vitro studies,
chitosan solutions were found to bind 38.5% of the indoxyl sulfate and 17.8% of
the phosphate, respectively. Further, the oxidized albumin ratio was correlated
with serum indoxyl sulfate levels in vivo. These results suggest that the
ingestion of chitosan results in a significant reduction in the levels of pro
oxidants, which include uremic toxins, in the gastrointestinal tract, thereby
inhibiting the subsequent development of oxidative stress in the systemic
circulation. In addition, the long-term ingestion of chitosan has the potential
for use in treating hyperphosphatemia in hemodialysis patients.
PMID- 25129730
TI - Light-induced surface graft polymerizations initiated by an anthraquinone dye on
cotton fibers.
AB - Anthraquinone and its derivatives could serve as photo-sensitizers and generate
radicals and reactive oxygen species in polymers under exposure of UVA or day
light. Such a property was utilized in development of novel light-induced surface
radical graft polymerizations on cotton fibers that were dyed with an
anthraquinone derivative, 2-ethylanthraquinone. Several functional monomers were
directly grafted onto the dyed cotton fibers upon UVA exposure. The chemical and
morphological structures and thermal properties of the grafted fibers were
confirmed and characterized by Fourier transform infrared spectrometer (FTIR),
scanning electron microscope (SEM) and thermal gravimetric analysis (TGA).
Reaction conditions including concentrations of the photosensitizer, the amount
of monomers, as well as UVA irradiation time could influence grafting
efficiencies. More interestingly, the surface graft polymerization did not
significantly change the light active functions of the agent, evidenced by the
light-active antimicrobial functions of the grafted fibers.
PMID- 25129731
TI - Improvement of polyvinyl alcohol properties by adding nanocrystalline cellulose
isolated from banana pseudostems.
AB - Cellulose nanocrystals (CNCs) isolated from banana pseudostems fibers (BPF) of
the Pacovan variety were used as fillers in a polyvinyl alcohol (PVOH) matrix to
yield a nanocomposite. The fibers from the external fractions of the BPF were
alkaline bleached and hydrolyzed under acidic conditions (H2SO4 62% w/w, 70 min,
45 degrees C) to obtain CNCs with a length (L) of 135.0 +/- 12.0 nm and a
diameter (D) of 7.2 +/- 1.9 nm to yield an aspect ratio (L/D) of 21.2. The CNCs
were applied to PVOH films at different concentrations (0%, 1%, 3%, and 5% w/w,
dry basis). With higher concentrations of CNCs, the water-vapor barrier of the
films increased, while the optical properties changed very little. Increasing the
concentration of the CNCs up to 3% significantly improved the mechanical
properties of the nanocomposite.
PMID- 25129732
TI - Fucosylated chondroitin sulfate diversity in sea cucumbers: a review.
AB - Fucosylated chondroitin sulfate (FucCS) is structurally distinct
glycosaminoglycans found from the sea cucumber body wall consisted of chondroitin
sulfate type backbone with attached sulfated or non-sulfated fucose side chain.
Structurally this compound plays an important role in maintaining the body wall
integrity and possesses a wide spectrum of biological activities. Recently
several glycosaminoglycans' structures have been solved to elucidate its
physicochemical activity. The purpose of this review paper is to elaborate
existing structural properties and functions, reporting over 30 years and
systematically discussion herein.
PMID- 25129733
TI - Validation of lignocellulosic biomass carbohydrates determination via acid
hydrolysis.
AB - This work studied the two-step acid hydrolysis for determining carbohydrates in
lignocellulosic biomass. Estimation of sugar loss based on acid hydrolyzed sugar
standards or analysis of sugar derivatives was investigated. Four model
substrates (starch, holocellulose, filter paper and cotton) and three levels of
acid/material ratios (7.8, 10.3 and 15.4, v/w) were studied to demonstrate the
range of test artifacts. The method for carbohydrates estimation based on acid
hydrolyzed sugar standards having the most satisfactory carbohydrate recovery and
relative standard deviation. Raw material and the acid/material ratio both had
significant effect on carbohydrate hydrolysis, suggesting the acid to have
impacts beyond a catalyst in the hydrolysis. Following optimal procedures, we
were able to reach a carbohydrate recovery of 96% with a relative standard
deviation less than 3%. The carbohydrates recovery lower than 100% was likely due
to the incomplete hydrolysis of substrates, which was supported by scanning
electron microscope (SEM) images.
PMID- 25129734
TI - Crosslinking chitosan into H3PO4/HNO3-NANO2 oxidized cellulose fabrics as
antibacterial-finished material.
AB - The primary hydroxyl groups on C6 position in glucose units of cellulose with
H3PO4/HNO3-NaNO2 mediated oxidation produced monocarboxy cellulose and binding
sites, subsequent amide reaction with chitosan solution to obtain chitosan
crosslinked cotton fabrics. Scanning electron microscope and FT-IR spectroscopy
were used to detect the fiber morphology and chemical bonding between chitosan
and oxidized cellulose, respectively. The influences of H3PO4/HNO3-NaNO2
oxidation and chitosan treatment on physical properties of cotton fabrics were
examined by determining carboxyl content, weight loss and mechanical properties
of fabrics, as well as chitosan content in the composite fabrics. Antibacterial
performance of chitosan-cellulose fabrics against Escherichia coli and
Staphylococcus aureus was evaluated. As a result, chitosan was bonded into cotton
fiber via the amido bond of CN formed between amino groups of chitosan and
carboxyl groups on oxidized cellulose, and these resultant chitosan-cotton
fabrics showed high antimicrobial activity and excellent antibacterial washing
durability.
PMID- 25129735
TI - Green synthesis of silver and copper nanoparticles using ascorbic acid and
chitosan for antimicrobial applications.
AB - Silver and copper nanoparticles were produced by chemical reduction of their
respective nitrates by ascorbic acid in the presence of chitosan using microwave
heating. Particle size was shown to increase by increasing the concentration of
nitrate and reducing the chitosan concentration. Surface zeta potentials were
positive for all nanoparticles produced and these varied from 27.8 to 33.8 mV.
Antibacterial activities of Ag, Cu, mixtures of Ag and Cu, and Ag/Cu bimetallic
nanoparticles were tested using Bacillus subtilis and Escherichia coli. Of the
two, B. subtilis proved more susceptible under all conditions investigated.
Silver nanoparticles displayed higher activity than copper nanoparticles and
mixtures of nanoparticles of the same mean particle size. However when compared
on an equal concentration basis Cu nanoparticles proved more lethal to the
bacteria due to a higher surface area. The highest antibacterial activity was
obtained with bimetallic Ag/Cu nanoparticles with minimum inhibitory
concentrations (MIC) of 0.054 and 0.076 mg/L against B. subtilis and E. coli,
respectively.
PMID- 25129736
TI - Amberlyst 15 as a new and reusable catalyst for the conversion of cellulose into
cellulose acetate.
AB - The acetylation of cellulose using sulfonated Amberlyst 15 as a new and reusable
catalyst was investigated. Optimization of the acetylation process was carried
out by variation in the amount of added catalyst, acetic acid, and acetic
anhydride as well as the reaction conditions, which includes reaction time and
reaction medium. Cellulose acetate, with a degree of substitution (DS) value of
2.38 and yield of 54.1%, was obtained under the optimized conditions and
characterized using Fourier-transform infrared (FTIR) spectroscopy,
thermogravimetric analysis-derivative thermogravimetry (TGA-DTG), and
differential scanning calorimetry (DSC). The sulfonated polymer catalyst could be
easily recovered by centrifugation after acetylation. Both the fresh and
recovered catalysts were characterized by means of FTIR, TGA-DTG, DSC, and
scanning electron microscopy (SEM), and the recovered catalyst could be
successfully reused without further treatment. It was found that Amberlyst 15
possessed excellent catalytic stability, no significant changes in the DS values,
and consistent yields of cellulose acetate observed over four reaction cycles.
PMID- 25129737
TI - Starch granules as a vehicle for the oral administration of immobilized antigens.
AB - Microparticles of diverse compositions are often used as carriers for interesting
antigens. In this work, we propose the use of natural microparticulated starch as
a vehicle for antigens. The proposed system is composed of raw starch
microparticles and a starch-binding domain that when fused to another protein,
allows for a stable protein immobilization onto the granule surface. To
demonstrate the use of starch as an antigen carrier, a fusion combining fragment
C of the tetanus toxin with the starch-binding domain was adsorbed to starch and
administered orally to mice in two different doses and, importantly, without the
use of any adjuvant. The results showed that the system allows the induction of
specific antibodies; moreover mice given this immobilized protein presented a
delay in the onset of tetanus symptoms compared to mice administered the non
immobilized protein. The study outlines the viability of this immobilization
system as an antigen and protein carrier.
PMID- 25129738
TI - Inducing PLA/starch compatibility through butyl-etherification of waxy and high
amylose starch.
AB - In this study, waxy and high amylose starches were modified through butyl
etherification to facilitate compatibility with polylactide (PLA). Fourier
transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy
and wettability tests showed that hydrophobic butyl-etherified waxy and high
amylose starches were obtained with degree of substitution values of 2.0 and 2.1,
respectively. Differential scanning calorimetry, tensile testing, and scanning
electron microscopy (SEM) demonstrated improved PLA/starch compatibility for both
waxy and high amylose starch after butyl-etherification. The PLA/butyl-etherified
waxy and high amylose starch composite films had higher tensile strength and
elongation at break compared to PLA/non-butyl-etherified composite films. The
morphological study using SEM showed that PLA/butyl-etherified waxy starch
composites had a more homogenous microstructure compared to PLA/butyl-etherified
high amylose starch composites. Thermogravimetric analysis showed that PLA/starch
composite thermal stability decreased with starch butyl-etherification for both
waxy and high amylose starches. This study mainly demonstrates that PLA/starch
compatibility can be improved through starch butyl-etherification.
PMID- 25129739
TI - Electrosprayed inulin microparticles for microbiota triggered targeting of colon.
AB - Inulin, a naturally occurring polysaccharide, was acetylated to make it
processable by electrospraying, a facile and single step method for microparticle
fabrication. Electrospraying process parameters were optimized for fabrication of
spherical and monodisperse indomethacin (IDM) loaded inulin acetate (INA)
microparticles. The apparent entrapment efficiency of IDM was determined to be
100%, whereas working encapsulation efficiency was estimated to be 35.39 +/-
1.63%. Differential scanning calorimetry and X-ray diffraction analysis confirmed
molecular dispersion of IDM in an amorphous state within the INA matrix. Finally,
the results from in vitro release study performed in simulated gastro-intestinal
fluids demonstrated that IDM was released only in simulated colonic fluid that
contained inulinase. Therefore, this study demonstrates that acetylation of
inulin does not alter its susceptibility to inulinase and that microparticles
fabricated from INA can be developed as a colon targeting drug delivery system.
PMID- 25129741
TI - Characterization of an amylose-graft-poly(n-butyl methacrylate) copolymer
obtained by click chemistry by EPR and SS-NMR spectroscopies.
AB - We present an investigation of the main chemical and physico-chemical properties
of a graft copolymer of amylose and poly(n-butyl methacrylate), Am-g-PBMA,
amphiphilic and able to self-assemble in water, prepared by coupling end azide
functionalized PBMA and alkyne-functionalized amylose under convenient click
conditions. A deep knowledge of these properties is necessary in the perspective
of real applications of the copolymer. To this aim we combined a basic
characterization through FT-IR, TGA, ICP-OES and SEM with an extensive EPR and
Solid State NMR investigation. It was possible to characterize the main
structural and dynamic properties of Am-g-PBMA and highlight the presence of
residual copper (Cu(II)) from the catalyst, even after an extensive purification
procedure. We could identify two main species of Cu(II): Cu(II) complexes
coordinated to the N,N,N',N'',N''-pentamethyldiethylenetriamine (PMDETA) ligand
from the catalyst and to the copolymer triazole nitrogens and multi-nuclear or
clustered Cu(II) species likely coordinated to amylose hydroxyl groups.
PMID- 25129740
TI - Alginate based hybrid copolymer hydrogels--influence of pore morphology on cell
material interaction.
AB - Alginate based hybrid copolymer hydrogels with unidirectional pore morphology
were prepared to achieve synergistic biological performance for cardiac tissue
engineering applications. Alginate based hybrid copolymer (ALGP) were prepared
using alginate and poly(propylene fumarate) (HT-PPF) units. Different hybrid
bimodal hydrogels were prepared by covalent crosslinking using poly(ethylene
glycol diacrylate) and vinyl monomer viz acrylic acid, methyl methacrylate, butyl
methacrylate and N-N'-methylene-bis-acrylamide and ionic crosslinking with
calcium. The morphologically modified hydrogels (MM-hydrogels) with
unidirectional elongated pores and high aspect ratio were prepared. MM-hydrogels
favour better mechanical properties; it also enhances cell viability and
infiltration due to unidirectional pores. However, the crosslinkers influence the
fibroblast infiltration of these hydrogels. Synthesis of collagen and fibroblast
infiltration was greater for alginate copolymer crosslinked with poly(ethylene
glycol diacrylate-acrylic acid (ALGP-PA) even after one month (288%). This hybrid
MM-hydrogel promoted cardiomyoblast growth on to their interstices signifying its
potent applications in cardiac tissue engineering.
PMID- 25129742
TI - Nanostructured membranes based on native chitin nanofibers prepared by mild
process.
AB - Procedures for chitin nanofiber or nanocrystal extraction from Crustaceans modify
the chitin structure significantly, through surface deacetylation, surface
oxidation and/or molar mass degradation. Here, very mild conditions were used to
disintegrate chitin fibril bundles and isolate low protein content individualized
chitin nanofibers, and prepare nanostructured high-strength chitin membranes.
Most of the strongly 'bound' protein was removed. The degree of acetylation,
crystal structure as well as length and width of the native chitin microfibrils
in the organism were successfully preserved. Atomic force microscopy and scanning
transmission electron microscopy, showed chitin nanofibers with width between 3
and 4 nm. Chitin membranes were prepared by filtration of hydrocolloidal
nanofiber suspensions. Mechanical and optical properties were measured. The
highest data so far reported for nanostructured chitin membranes was obtained for
ultimate tensile strength, strain to failure and work to fracture. Strong
correlation was observed between low residual protein content and high tensile
properties and the reasons for this are discussed.
PMID- 25129743
TI - Bio-inspired Aloe vera sponges for biomedical applications.
AB - Chemical composition and biological properties of Aloe vera (AV), a tropical
plant, explain its potential use for cosmetic, nutritional and biomedical
applications. AV gel present in AV leaves is rich in several compounds, nutrients
and polysaccharides. This work proposes using AV gel complex structure and
chemical composition, associated with freeze-drying, to produce sponges. To
increase the structures stability in aqueous media, a thin coating of gellan gum
(GG), was applied onto AV gel. AV-based sponges showed a heterogeneous porous
formation, interconnected pores and good porosity (72-77%). The coating with a GG
layer onto AV influenced the stability, swelling behavior and mechanical
properties of the resulting sponges. Moreover, sponges provided the sustained
release of BSA-FTIC, used as a model protein, over 3 weeks. Also, in vitro cell
culture studies evidenced that sponges are not cytotoxic for a mouse fibroblast
like cell line. Therefore, developed AV-based sponges have potential use in
biomedical applications.
PMID- 25129745
TI - Preparation of aligned porous chitin nanowhisker foams by directional freeze
casting technique.
AB - Structured biofoams with aligned porous structures were fabricated from nanosized
chitin by employing a directional freeze-casting technique. The effects of the
freezing conditions and slurry formulation on nanochitin foam morphology were
investigated. The morphology of obtained foams was characterized using scanning
electron microscopy (SEM). It was found that the pore structure of the obtained
foams was a likewise of the ice crystals formed during the directional freezing.
The results indicate that directional freeze-casting protocol can significantly
influence the morphological features and microstructures of the obtained biofoams
which could have numerous applications, including engineered carriers, scaffolds,
filters and specifically as a template for potential multi-layered composites
after infusion with a second phase.
PMID- 25129746
TI - Aqueous counter collision using paired water jets as a novel means of preparing
bio-nanofibers.
AB - This study involved a detailed investigation of a novel approach to reducing
naturally occurring cellulose fibers into nanofibers solely by the use of aqueous
counter collision (ACC) without any chemical modification. In this process,
equivalent aqueous suspensions of cellulose are ejected from dual nozzles and
collide at high speed and pressure. Even a few repetitions of the collision
process are sufficient to produce nano-sized fibers dispersed in water. This work
compared the ACC nano-pulverization of stable Ibeta-rich and meta-stable Ialpha
rich cellulose samples. The ACC method is applicable to various kinds of
polymeric materials with hierarchical structures, either natural or synthetic, as
a means of preparing aqueous dispersions of nano-sized structures.
PMID- 25129744
TI - Enhanced multiparametric hyaluronan degradation for production of molar-mass
defined fragments.
AB - Hyaluronic acid (HA) is known to serve as a dynamic mediator intervening in many
physiological functions. Its specific effect has been repeatedly confirmed to be
strongly influenced by the molecular size of hyaluronan fragments. However common
technological approaches of HA fragments production have their limitations. In
many cases, the final products do not meet the strict pharmaceutical
requirements, specifically due to size polydispersity and reaction contaminants.
We present novel methodology based on combination of unique incidental ability of
the plant-derived protease papain to split the glycosidic bonds and an
indispensable advantages of biocompatible macroporous material with incorporated
ferrous ions serving as carrier for covalent papain fixation. This atypical and
yet unpublished highly efficient multiparametric approach allows enhanced HA
fragmentation for easily and safely producing molar-mass-defined HA fragments
with narrow size distribution. Native polyacrylamide gel electrophoresis (PAGE)
and size exclusion chromatography/multi-angle light scattering (SEC-MALS)
confirmed the effectiveness of our multiparametric approach.
PMID- 25129747
TI - Durability and synergistic effects of KI on the acid corrosion inhibition of mild
steel by hydroxypropyl methylcellulose.
AB - The performance of hydroxypropyl methylcellulose (HPMC) as safe corrosion
inhibitor for mild steel in aerated 0.5M H2SO4 solution was appraised by weight
loss, impedance and polarization measurements. Results indicate that HPMC
functions as a good inhibitor in the studied environment and inhibition
efficiency increased with increasing concentration of inhibitor and temperature.
Time-dependent effect of the inhibition efficiency reveals that inhibition
efficiency increased with time up to the fourth day after which it waned, but
improved on addition of KI. The synergism parameter evaluated confirmed the
synergistic effect of KI and HPMC. Impedance results clearly show that HPMC
inhibited the corrosion reaction via adsorption onto the metal/solution interface
following Freundlich adsorption isotherm. Polarization results indicate that HPMC
acts as a mixed-type inhibitor with predominant cathodic effect. Theoretical
study using density functional theory was employed to establish the correlation
between the structure (molecular and electronic) and the inhibition efficiency.
PMID- 25129748
TI - Chemical studies on the polysaccharides of Salicornia brachiata.
AB - A group of 12 polysaccharide extracts were prepared from the tips, stem and roots
of an Indian halophyte Salicornia brachiata Roxb. obtained by sequential
extractions with cold water (CW), hot water (HW), aqueous ammonium oxalate (OX)
and aqueous sodium hydroxide (ALK) solutions. Monosaccharide composition analysis
revealed that all the polysaccharide extract samples consisted primarily of
rhamnose, arabinose, mannose, galactose, glucose, whereas ribose and xylose were
present only in some of the extracts. All the extracts exhibited low apparent
viscosity (1.47-2.02 cP) and sulphate and contained no prominent toxic metal
ions. Fucose was detected only in OX extract of the roots. These polysaccharides
were found to be heterogeneous and highly branched (glycoside linkage analysis,
size-exclusion chromatography, (13)C-NMR, FT-IR, circular dichroism and optical
rotation data). Physico-chemical analyses of these polysaccharides including
uronic acid, sulphate and protein contents were also carried out. This
constitutes the first report on the profiling of Salicornia polysaccharides.
PMID- 25129749
TI - Modification of pine pulp during oxygen delignification by xylan self-assembly.
AB - Self-assembly is a technique of preparing functional materials based on targeted
intermolecular interactions involving different macromolecules. In this work,
hardwood xylan was disassembled from wood and birch bleached kraft pulp using
pressurized hot water extraction (HWX) and cold alkali extraction (CAX),
respectively. The extracted biopolymers were characterized using gas
chromatography (GC), size exclusion chromatography (SEC) and Fourier transform
infrared spectroscopy (FTIR), and subsequently added into an oxygen
delignification reactor containing pine kraft pulp. The assembly of xylan-pulp
fiber was characterized using advanced time-of-flight secondary ion mass
spectrometry (ToF-SIMS) and imaging. The xylan-pine pulp assembly was not
significantly removed during the whole elemental chlorine free bleaching sequence
or during low consistency refining. Modified fibers had superior mechanical
properties compared to the reference pulp. Our concept can be easily applied in
the pulp and paper industry, and it opens new possibilities for the utilization
of fully bio-based fibers in new materials.
PMID- 25129750
TI - Evolution of amylopectin structure in developing wheat endosperm starch.
AB - In this study, starches extracted from wheat grains harvested at 7, 14, 28, and
35 days after anthesis (DAA) were used as a means of examining the molecular
structure of amylopectin (AP) from developing wheat grain. Scanning electron
microscopy of wheat grain cross-sections revealed the presence of endosperm at 7
DAA and contained lenticular-shaped developing large (A-type) granules. From 14
DAA onward, spherical-shaped small (B-type) granules coexisted with large
granules in the endosperm. During granule development, the fine structure of AP
varied with maturity in both large and small granules. Towards the end of the pre
physiological maturity stage (28 DAA), AP in small and large granules had
shortest external chain length (ECL), longest internal chain length (ICL) and
lowest amount of A-chains. At physiological maturity (35 DAA), these changes in
ECL, ICL and amount of A-chains were reversed when compared to 28 DAA. In both
large and small granules, the external AP structure was apparently more organized
at physiological maturity than at pre-physiological maturity.
PMID- 25129751
TI - Structure of clusters and building blocks in amylopectin from developing wheat
endosperm.
AB - Changes in internal structure of amylopectin (AP) during wheat endosperm
development were studied by isolating clusters and building blocks of AP from
both large A-type and small B-type starch granules at different maturity stages
up to harvest time at 49 days after anthesis (DAA). Clusters isolated from B-type
granules had a degree of branching (DB) of 16.5-16.8% and were more tightly
branched than those isolated from A-type granules (DB 15.7-16.2%). The degree of
polymerization (DP) of the clusters increased in both types of granules during
the pre-physiological maturity stage up to 28 DAA. Clusters at maturity were
smaller with less branches and building blocks than at the end of the pre
maturity stage. It is suggested that this was due to a continuous trimming of the
cluster structure after the active period of starch synthesis. Differences were
evident between A- and B-type granules with regards to glucan trimming and the
type of new chains produced.
PMID- 25129753
TI - Synthesis and characterization of cellulose acetate from rice husk: eco-friendly
condition.
AB - Cellulose acetate was synthesized from rice husk by using a simple, efficient,
cost-effective and solvent-free method. Cellulose was isolated from rice husk
(RH) using standard pretreatment method with dilute alkaline and acid solutions
and bleaching with 2% H2O2. Cellulose acetate (CA) was synthesized successfully
with the yield of 66% in presence of acetic anhydride and iodine as a catalyst in
eco-friendly solvent-free conditions. The reaction parameters were standardized
at 80 degrees C for 300 min and the optimum results were taken for further
study. The extent of acetylation was evaluated from % yield and the degree of
substitution (DS), which was determined by (1)H NMR and titrimetrically. The
synthesized products were characterized with the help modern analytical
techniques like FT-IR, (1)H NMR, XRD, etc. and the thermal behavior was evaluated
by TGA and DSC thermograms.
PMID- 25129752
TI - Stretching properties of xanthan and hydroxypropyl guar in aqueous solutions and
in cosmetic emulsions.
AB - Filament stretchability of xanthan gum (XG) and hydroxypropyl guar (HPG) was
investigated in aqueous solutions (0.125, 0.25, 0.5, 1, 1.2 and 1.5% w/w) and in
O/W emulsions using a texture analyzer. Additionally, rheological
characterizations were carried out on the systems and shear and oscillation
parameters were used to interpret stretching properties. XG solutions exhibited a
solid-like behavior with rheological parameters much higher than for HPG one
whatever the concentration. Filament stretching values of XG solutions were
superior to HPG for concentration below 1% w/w and then became comparable for
higher concentrations. No meaningful relationship was found between rheological
and stretching values. Synergy was observed for all XG/HPG mixtures at 0.125,
0.25 and 0.5% influencing both the rheological and the filament stretching
values. The 25/75 XG/HPG ratio showed the maximum synergistic effect at all
concentrations while the filament stretchability was enhanced in a wider range of
ratios. XG and HPG did not present the same behavior in emulsions. No clear
synergistic effect was observed and XG markedly influenced the emulsion filament
stretching.
PMID- 25129754
TI - Viscoelastic behavior of maize kernel studied by dynamic mechanical analyzer.
AB - The creep recovery, stress relaxation, temperature-dependence and their frequency
dependence of maize kernel were determined within a moisture content range of
11.9% to 25.9% (w/w) by using a dynamic mechanical analyzer. The 4-element
Burgers model was found to adequately represent the creep behavior of the maize
seeds (R(2)>0.97). The 5-element Maxwell model was able to better predict the
stress relaxation behavior of maize kernel than the 3-element Maxwell model. The
Tg values for the maize kernels decreased with increased moisture content. For
example, the Tg values were 114 degrees C and 65 degrees C at moisture content
values of 11.9% (w/w) and 25.9% (w/w), respectively. The magnitude of the loss
moduli and loss tangent and their rate of change with frequency were highest at
20.7% and lowest at 11.9% moisture contents. The maize kernel structure exhibited
A-type crystalline pattern and the microstructure was found to expand with
increase in moisture content.
PMID- 25129755
TI - Ginsenoside compound K-bearing glycol chitosan conjugates: synthesis,
physicochemical characterization, and in vitro biological studies.
AB - Ginsenosides are triterpenoids found in Panax ginseng and have a numerous
structural, functional, and pharmacological properties. The purpose of this study
was to develop hydrophilic polymer functionalized ginsenoside conjugates to
enhance water solubility and targeted delivery. To this end, hydrophobic
ginsenoside compound K (CK) was covalently conjugated to the backbone of
hydrophilic glycol chitosan (GC) through an acid-labile linkage. The resulting GC
CK conjugates formed self-assembled spherical nanoparticles in an aqueous
solution, and their particles sizes were (296 nm and 255 nm) dependent on the
degree of CK substitution. The nanoparticles were stable in the physiological
buffer (pH 7.4) over a period of 8 days, whereas they were readily degraded under
acidic conditions (pH 5.0) mimicking the intracellular pH-conditions. From in
vitro release experiment, it was found that CK released slowly from the self
assembled nanoparticles in the physiological buffer (pH 7.4). On the other hand,
the release rate of CK was rapidly increased under the acidic condition (pH 5.0).
In vitro cytotoxicity assays revealed that GC-CK conjugates exhibited higher
cytotoxicity than CK in HT29, and similar cytotoxicity in HepG2, and HT22 cell
lines. Moreover, RAW264.7 cells treated with GC-CK maintained good cell viability
and exhibited decreased lipopolysaccharide-induced NO production. Taken together,
these results suggest that the GC-CK conjugate may be potentially useful as a
tumor-specific delivery vehicle.
PMID- 25129756
TI - Carboxymethylcellulose film for bacterial wound infection control and healing.
AB - Infection control and wound healing profiles of sodium carboxymethylcellulose
(SCMC) films were investigated as a function of their anti-bacterial action,
physical structures, polymer molecular weights and carboxymethyl substitution
degrees. The films were prepared with in vitro polymer/film and in vivo microbe
colonized wound healing/systemic infection profiles examined. Adhesive high
carboxymethyl substituted SCMC films aided healing via attaching to microbes and
removing them from wound. Pseudomonas aeruginosa was removed via encapsulating in
gelling low molecular weight SCMC film, whereas Staphylococcus aureus was trapped
in tight folds of high molecular weight SCMC film. Incomplete microbe removal
from wound did not necessary translate to inability to heal as microbe remnant at
wound induced fibroblast migration and aided tissue reconstruction. Using no film
nonetheless will cause systemic blood infection. SCMC films negate infection and
promote wound healing via specific polymer-microbe adhesion, and removal of S.
aureus and P. aeruginosa requires films of different polymer characteristics.
PMID- 25129757
TI - Transdermal delivery of 10,11-methylenedioxycamptothecin by hyaluronic acid based
nanoemulsion for inhibition of keloid fibroblast.
AB - This study designs an alternative transdermal delivery system for 10,11
methylenedioxycamptothecin(MD-CPT) to inhibit keloid. Hyaluronic acid
nanoemulsions (HANs) with nano size, negative charge and good stability were
prepared as transdermal carriers. The MD-CPT loaded HANs performed desirable skin
permeable capacity across human keloid skin and the drug was transferred directly
to keloid lesion area. MD-CPT was delivered percutaneously higher than the
control group. FITC-HANs could be successfully internalized by keloid fibroblast
(KF) and deliver MD-CPT toward nucleus, inhibited the proliferation of KF, while
there was no serious toxicity to normal skin fibroblasts. The growth-inhibitory
effect was further clarified upon cell cycle regulation, which arrested cells at
G1/S and prevented them entry into mitosis. KF gene expression demonstrated
plasminogen activator inhibitor-1 (PAI-1) was significantly down-regulated and
Smad7 up-regulated, which was beneficial to inhibit keloid. The study
demonstrated that as transdermal delivery of MD-CPT by HANs has potential for
inhibition of keloid fibroblast.
PMID- 25129758
TI - Biosynthesis of oligodextrans with different Mw by synergistic catalysis of
dextransucrase and dextranase.
AB - In this study, we have investigated various adding times of dextranase to the
dextransucrase system to reveal the synergistic process of dextransucrase and
dextranase. Dextranase added into the dextransucrase-sucrose system at different
times gave rise to different main dextran products. The results showed that
dextranase added into sucrose system at the same time with dextransucrase
synthesized low molecular weight (Mw) dextran targeted to 5 kDa, while dextranase
added during the reaction process of dextransucrase directionally prepared
dextran with medium Mw of 10 kDa and 20 kDa. Fourier-transform infrared (FTIR)
spectroscopy and (1)H Nuclear magnetic resonance (NMR) exhibited that the
synthesized oligodextrans were mainly composed of alpha-1,6-glycosidic linkages
(dextran 6587 Da, 96.82%; dextran 22,521 Da, 96.03%) and low alpha-1,3-glycosidic
branch. The research established the relationship between the synergistic
catalysis of the double enzymatic system and the synthesis of oligodextrans with
different Mw.
PMID- 25129759
TI - Optimum extraction of polysaccharides from motherwort leaf and its antioxidant
and antimicrobial activities.
AB - Box-Behnken design was employed to optimize the extraction conditions for
polysaccharides from the leaves of motherwort (Leonurus cardiaca L.). Three
independent variables including extraction temperature (60-100 degrees C),
extraction time (60-120 min), and the ratio of water to raw material (20-60) were
investigated. The results revealed that the quadratic and linear terms of three
factors had strong effects on the extraction yield of polysaccharides from
motherwort leaf. The best extraction conditions for the yield of polysaccharide
(LCLP) was extraction temperature of 81.4 degrees C, time of 106.6 min and the
ratio of water to raw material of 45.2. Under the optimal conditions, the
extraction yield of LCLP was 9.17 +/- 0.39%, which was well matched with value
predicted by the model 9.26%. The results indicated that the purified LCLP
exerted obvious scavenging effects on free radicals in vitro. Furthermore,
motherwort polysaccharides could be used as a novel antimicrobial additive.
PMID- 25129760
TI - Purification and structural data of a highly substituted exopolysaccharide from
Pseudomonas stutzeri AS22.
AB - Pseudomonas stutzeri AS22, when grown on media containing starch and yeast
extract and incubated at 30 degrees C and 200 rpm for 24h, was found to produce
an acidic and high-molecular mass exopolysaccharide (EPS22). The EPS22 was
purified and a yield of 1.3g/l was achieved. The average molecular mass of the
EPS22 was determined by high-performance size-exclusion chromatography (HPSEC)
and showed an average molecular mass of 9.9 * 10(5)Da and a polydispersity index
Mw/Mn (Mw, weight-average and Mn, number-average) of 1.197 +/- 0.015. Structural
data of this EPS22 were determined using a combination approach including
monosaccharide composition (HPAEC-PAD and GLC), methylation analysis (GC-MS) and
NMR spectroscopy analysis. EPS22 was found to be a complex heteropolysaccharide
with a repeating unit mainly composed of glucose, mannose and lactyl rhamnose in
a molar ratio of 1:1.1:0.7. The acidic nature of the polysaccharide is due to the
presence of three non-osidic substituents consisting of a lactyl, acetyl, and
pyruvyl groups.
PMID- 25129761
TI - Hydroxyl radical-induced crosslinking and radiation-initiated hydrogel formation
in dilute aqueous solutions of carboxymethylcellulose.
AB - Ionizing radiation causes chain scission of polysaccharides in the absence of
crosslinking agents. It has been demonstrated before that degradation of
carboxyalkylated polysaccharides may be prevented, despite presence of strong
electrostatic repulsing forces between chains, at very high polymer concentration
in water (paste-like state) when physical proximity promotes recombination of
radiation-generated polymer radicals. In such conditions, crosslinking dominates
over chain scission and covalent, macroscopic gels can be formed. In an approach
proposed in this work, neutralizing the charges on carboxymethylcellulose (CMC)
by lowering the pH results in retracting the electrostatic repulsion between
chain segments and thus allows for substantial reduction of polymer concentration
required to achieve gelation due to domination of crosslinking reactions.
Electron-beam irradiation of aqueous solutions of low pH containing 0.5-2% CMC
results in hydrogel formation with 70% yield, while both concentration and dose
determine their swelling properties. Time-resolved studies by laser flash
photolysis clearly indicate strong pH influence on decay kinetics of CMC
radicals.
PMID- 25129762
TI - Removing polysaccharides-and saccharides-related coloring impurities in alkyl
polyglycosides by bleaching with the H2O2/TAED/NaHCO3 system.
AB - The effect of H2O2/TAED/NaHCO3 system, namely NaHCO3 as alkaline agent with the
(tetra acetyl ethylene diamine (TAED)) TAED-activated peroxide system, bleaching
of alkyl polyglycosides solution was studied by spectrophotometry. The results
showed that the optimal bleaching conditions about H2O2/TAED/NaHCO3 system
bleaching of alkyl polyglycosides solution were as follows: molar ratio of TAED
to H2O2 was 0.06, addition of H2O2 was 8.6%, addition of NaHCO3 was 3.2%,
bleaching temperature of 50-65 degrees C, addition of MgO was 0.13%, and
bleaching time was 8h. If too much amount of NaHCO3 was added to the system and
maintained alkaline pH, the bleaching effect would be greatly reduced. Fixing
molar ratio of TAED to H2O2 and increasing the amount of H2O2 were beneficial to
improve the whiteness of alkyl polyglycosides, but adding too much amount of H2O2
would reduce the transparency. In the TAED-activated peroxide system, NaHCO3 as
alkaline agent and buffer agent, could overcome the disadvantage of producing
black precipitates when NaOH as alkaline agent.
PMID- 25129763
TI - Correlation of chemical, structural and thermal properties of natural fibres for
their sustainable exploitation.
AB - The potential of lignocellulosic natural fibres as renewable resources for
thermal conversion and material reinforcement is largely dependent on the
correlation between their chemical composition, crystalline structure and thermal
decomposition properties. Significant differences were observed in the chemical
composition of cotton, flax, hemp, kenaf and jute natural fibres in terms of
cellulose, hemicellulose and lignin content, which influence their morphology,
thermal properties and pyrolysis product distribution. A suitable methodology to
study the kinetics of the thermal decomposition process of lignocellulosic fibres
is proposed combining different models (Friedman, Flynn-Wall-Ozawa, Criado and
Coats-Redfern). Cellulose pyrolysis can be modelled with similar kinetic
parameters for all the natural fibres whereas the kinetic parameters for
hemicellulose pyrolysis show intrinsic differences that can be assigned to the
heterogeneous hemicellulose sugar composition in each natural fibre. This study
provides the ground to critically select the most promising fibres to be used
either for biofuel or material applications.
PMID- 25129764
TI - Rheological properties of micro-/nanofibrillated cellulose suspensions: wall-slip
and shear banding phenomena.
AB - The rheological properties of enzymatically hydrolyzed and TEMPO-oxidized
microfibrillated/nanofibrillated cellulose (MFC/NFC) aqueous suspensions were
investigated in oscillation and steady-flow modes and were compared with the
morphology of the studied materials. The flow instabilities, which introduce an
error in the rheological measurements, were discovered during flow measurements.
A wall-slip (interfacial slippage on the edge of geometry tools and suspension)
was detected at low shear rates for two types of NFC suspensions while applying
cone-plate geometry. A roughening of the tool surfaces was performed to overcome
the aforementioned problem. Applying to TEMPO-oxidized NFC, a stronger suspension
response was detected at low shear rates with higher values of measured shear
stress. However, a shear banding (localization of shear within a sample volume)
became more pronounced. The use of serrated tools for enzymatically hydrolyzed
NFC produced lower shear stress at the moderate shear rates, which was influenced
by water release from the suspension.
PMID- 25129765
TI - Molecular self assembly of mixed comb-like dextran surfactant polymers for SPR
virus detection.
AB - The synthesis of two comb-like dextran surfactant polymers, that are different in
their dextran molecular weight (MW) distribution and the presence of carboxylic
groups, and their characterization are reported. A bimodal carboxylic dextran
surfactant polymer consists of poly(vinyl amine) (PVAm) backbone with carboxyl
higher MW dextran, non-functionalized lower MW dextran and hydrophobic hexyl
branches; while a monomodal dextran surfactant polymer is PVAm grafted with non
functionalized lower MW dextran and hexyl branches. Layer formation of non
covalently attached dextran chains with bimodal MW distributions on a surface
plasmon resonance (SPR) chip was investigated from the perspective of mixed
physisorption of the bimodal and monomodal surfactant polymers. Separation
distances between the carboxylic longer dextran side chains within the bimodal
surfactant polymer and between the whole bimodal surfactant molecules on the chip
surface could be well-controlled. SPR analysis of shrimp yellow head virus using
our mixed surfactant chips showed dependence on synergetic adjustment of these
separation distances.
PMID- 25129766
TI - Chemo-selective high yield microwave assisted reaction turns cellulose to green
chemicals.
AB - Exceptionally high cellulose liquefaction yields, up to 87% as calculated from
the amount of solid residue, were obtained under mild conditions by utilizing the
synergistic effect of microwave radiation and acid catalysis. The effect of
processing conditions on degradation products was fingerprinted by rapid laser
desorption ionization-mass spectrometry (LDI-MS) method. The reaction was chemo
tunable, enabling production of glucose (Glc) or levulinic acid (LeA) at
significantly high selectivity and yields, the relative molar yields being up to
50 and 69%, respectively. A turning point from pure depolymerization to glucose
to further degradation to levulinic acid and formic acid was observed at
approximately 50% liquefaction or above 140 degrees C. This was accompanied by
the formation of small amounts of solid spherical carbonized residues. The
reaction was monitored by multiple analytical techniques. The high yields were
connected to the ability of the process to break the strong secondary
interactions in cellulose. The developed method has great potential for future
production of green platform chemicals.
PMID- 25129767
TI - Analysis of isoamylase debranched starches with size exclusion chromatography
utilizing PFG columns.
AB - Debranched starches were tested with a previously developed method for size
exclusion chromatography (SEC) with multi detection utilizing different columns
than usually used for the separation of starch in DMSO. A number of debranched
starches were analyzed. This system allows good separation of amylose and
amylopectin after debranching of starch, and provides quantitative information on
the amylose content. Additionally molar mass versus hydrodynamic radii (Rh)
distributions of various debranched starches show that the debranching was not
100% and that the differences in the structure of various starches can be
followed.
PMID- 25129768
TI - Simple synthesis and chelation capacity of N-(2-sulfoethyl)chitosan, a taurine
derivative.
AB - This study presents a simple and effective synthesis method of N-(2
sulfoethyl)chitosan (NSE-chitosan) via a reaction between sodium 2
bromoethanesulfonate and chitosan that allows polymer transformation without
using additional reagents and organic solvents. The chemical structure of the
obtained NSE-chitosan was characterized by FT-IR and (1)H NMR spectroscopies.
Thermogravimetric study of NSE-chitosan coupled with FT-IR analysis has shown
stability of the polymer up to 200 degrees C, which almost does not change with
the increase of degree of substitution (DS). The sorption of transition and
alkaline earth metal ions from multicomponent solutions on NSE-chitosan was
investigated. The synthesized sorbents showed the selective recovery of silver(I)
and copper(II) ions from ammonium acetate buffer solution. The increase of DS
enhanced the selectivity to silver(I) ions sorption in comparison with copper(II)
ions. Selectivity coefficients K(Ag/Cu) increase from 1.3 to 10.9 with DS
increasing up to 0.7 (ammonium acetate buffer solution, pH 6.5). Sorption
isotherms of transition metal ions on NSE-chitosan with DS = 0.5 have been fitted
using Langmuir, Freundlich, and Redlich-Peterson models. The maximum sorption
capacities of sorbent in ammonium acetate buffer solution at pH 6.0 were 1.72
mmol/g for Cu(II), 1.23 mmol/g for Ag(I) and below 0.5 mmol/g for Co(II), Zn(II),
Cd(II), Pb(II), Mn(II) and Ni(II) ions.
PMID- 25129769
TI - An antioxidative galactomannan-protein complex isolated from fermentation broth
of a medicinal fungus Cs-HK1.
AB - A protein-containing polysaccharide, EPS2BW, was fractionated from the
exopolysaccharide (EPS) produced by a medicinal fungus Cordyceps sinensis (Cs
HK1). EPS2BW was mainly composed of galactomannan with about 16% (w/w) protein
and 50 kDa average molecular weight. The galactomannan part consisted of mannose
and galactose at 1.7:1.0 molar ratio, and the protein segments were composed of
sixteen amino acids with 12.5% proline and 16.6% threonine (mol%) being the most
abundant. Based on analytical results from NMR, methylation analysis, partial
acid hydrolysis and GC-MS, the galactomannan structure was elucidated as a (1 ->
2)-alpha-D-mannopyranosyl (Manp) backbone with O-6-linked galactopyranosyl (Galp)
branches. EPS2BW exhibited a high antioxidant capacity in both chemical and cell
culture assays, with a Trolox equivalent radical scavenging activity of 44.7
MUmol Trolox/mg, a Fe(3+) reducing power of 38.9 MUmol Fe(2+)/mg, and significant
cytoprotective effect against H2O2-induced PC12 cell death at 50-250 MUg/mL.
PMID- 25129770
TI - Characterization of glucomannan from Amorphophallus oncophyllus and its prebiotic
activity in vivo.
AB - Porang (Amorphophallus oncophyllus) is local perennial plant rich in glucomannan.
The aim of this study was to extract and characterize glucomannan from porang
tuber and to evaluate its potency as prebiotic in vivo. The research consisted of
the following steps, i.e. extraction of glucomannan, evaluation of its physico
chemical properties, and in vivo study. Extraction was done by immersing porang
fluor with water at 55 degrees C followed by coagulating glucomannan using
ethanol. Solubility, water holding capacity, viscosity, degree of acetylation,
degree of polymerization (DP), and purity of the glucomannan were evaluated. In
vivo study was done using thirty-two Wistar rats which were divided into four
groups. Each group was treated for 14 days with standard AIN 93 (standard),
porang glucomannan, commercial konjac glucomannan, and inulin diet as source of
fiber. Bacterial population and chemical properties of digesta were analyzed
after intervention. The results of the study indicated that the yield of
glucomannan from porang flour was 18.05% with 92.69% purity. Compared to
commercial glucomannan, porang glucomannan showed higher solubility (86.4%) and
degree of acetylation (13.7%), but lower viscosity (5400 cps), WHC (34.5 g/g),
and DP (9.4). Diet supplemented with porang glucomannan inhibited the growth of
Escherichia coli, enhanced the production of total SCFA, and reduced pH value of
cecal content. The study indicated that glucomannan from porang may be used as
functional food.
PMID- 25129771
TI - Effect of hyaluronic acid on the thermogelation and biocompatibility of its
blends with methyl cellulose.
AB - Aim of this work was to investigate the influence of hyaluronic acid (HA)
molecular weight on the thermogelation and biocompatibility of its blends with
methyl cellulose in view of a possible application in drug delivery and/or wound
healing. We found out that it was possible to obtain MC/HA blends showing a
rheological behavior typical of a viscous solution at 20 degrees C and of a weak
gel at 37 degrees C only when blending MC with low molecular weight HA.
Moreover, the blends containing low molecular weight HA did not affect human
foreskin fetal fibroblasts viability, proliferation and migration. On the
contrary, the cell incubation with high molecular weight HA resulted in a marked
and significant reduction of cell viability, compared to control cells. Finally,
the optimized blends, in terms of rheological properties and biocompatibility,
proved to be able to control and prolong bovine serum albumin release by a
combined mechanism of platform dissolution and drug diffusion.
PMID- 25129772
TI - The role of poly-M and poly-GM sequences in the metal-mediated assembly of
alginate gels.
AB - Whilst the involvement of poly-G sequences in the formation of metal-mediated
alginate gels has been previously studied in some detail, investigations into the
role of poly-M and poly-GM sequences has been relatively neglected. In this
regard, the binding of sodium and calcium ions to poly-M and poly-GM decamers,
and their influence on chain aggregation, has been modelled by conducting a
series of molecular dynamics simulations. This work complements a previous
analogous study carried out for the poly-G decamer, whereby up to three strands
are systematically introduced into each simulation. As in the previous study,
this method allows intrinsic binding modes and interchain structural motifs to be
revealed, that are consistent with those observed in available AFM images of
consolidated 3-D networks. It is apparent from these studies that different
sequences have different structural implications for metal-mediated chain
association.
PMID- 25129773
TI - Gas permeability and selectivity of cellulose nanocrystals films (layers)
deposited by spin coating.
AB - Cellulose nanocrystals (CNC) were extracted from a cellulose residue using two
different acid hydrolysis procedures. CNC extracted with sulfuric acid (CNC(S))
showed higher surface charge (339 MUmol/g) compared with crystals extracted with
hydrochloric acid (CNC(HCl)). Spin-coated films with two different configurations
were prepared; the first with alternate layers of poly(allylamine hydrochloride)
(PAHCl) and CNC, and the second with a single layer of PAHCl coated with
multilayers of CNC. Film characteristics such as roughness, thickness, contact
angle, orientation, gas permeability and gas selectivity were studied. Optical
microscopy showed more homogeneous films of CNC(S) compared to CNC(HCl). The
surface charge of the crystals impacted the films' hydrophobicity, being highest
for 25 alternate layers of PAHCl and CNC(HCl). The gas permeability coefficient
was different for each film, depending primarily on the surface charge of the
crystals and secondly on the film configuration. The films made with CNC(HCl)
displayed gas barriers with nitrogen and oxygen, and gas selectivity with some
gas combinations. CNC(S) films did not show gas selectivity. These results
indicate that CNC with low surface charge can be further developed for gas
separation and barrier applications.
PMID- 25129775
TI - Hydroxypropyl cellulose stabilizes amorphous solid dispersions of the poorly
water soluble drug felodipine.
AB - Overcoming the low oral bioavailability of many drugs due to their poor aqueous
solubility is one of the major challenges in the pharmaceutical industry. The
production of amorphous solid dispersions (ASDs) of these drugs using hydrophilic
polymers may significantly improve their solubility. However, their storage
stability and the stability of their supersaturated solutions in the
gastrointestinal tract upon administration are unsolved problems. We have
investigated the potential of a low viscosity grade of a cellulosic polymer,
hydroxypropyl cellulose (HPC-SSL), and compared it with a commonly used vinyl
polymer, polyvinylpyrrolidone vinyl acetate (PVP-VA), for stabilizing the ASDs of
a poorly water soluble drug, felodipine. The ASDs were produced using hot melt
mixing and stored under standard and accelerated stability conditions. The ASDs
were characterized using differential scanning calorimetry, powder X-ray
diffraction, and Fourier transform infrared spectroscopy. Drug dissolution and
partitioning rates were evaluated using single- and biphasic dissolution studies.
The ASDs displayed superior drug dissolution and partitioning as compared to the
pure crystalline drug, which might be attributed to the formation of a drug
polymer molecular dispersion, amorphous conversion of the drug, and drug-polymer
hydrogen bonding interactions. Late phase separation and early re-crystallization
occurred at lower and higher storage temperatures, respectively, for HPC-SSL
ASDs, whereas early phase separation, even at low storage temperatures, was noted
for PVP-VA ASDs. Consequently, the partitioning rates for ASDs dispersed in HPC
SSL were greater than those of PVP-VA at lower and room temperature storage,
whereas the performance of both of the ASDs was similar when stored at higher
temperatures.
PMID- 25129774
TI - Preparation and characterization of galactosylated alginate-chitosan oligomer
microcapsule for hepatocytes microencapsulation.
AB - Galactosylated alginate (GA)-chitosan oligomer microcapsule was prepared to
provide a sufficient mechanical stability, a selective permeability and an
appropriate three-dimensional (3D) microenvironment for hepatocytes
microencapsulation. The microcapsule has a unique asymmetric membrane structure,
with a dense layer located in the inner surface and gradually decreasing toward
the outside surface. The stable microcapsule was obtained when GA lower than 50%,
while the permeability was increased with increasing of GA. A balance between
mechanical stability and permeability was achieved through modulating membrane
porosity and thickness. The optimal microcapsule displays a selective
permeability allowing efficient transport of human serum albumin while
effectively blocking immunoglobulin G. Hepatocytes exhibited high and long term
viability (>92%), proliferability, multicellular spheroid morphology, and
enhancement of liver-specific functions in the microcapsule wherein galactose
moieties present chemical cues to support cell-matrix interactions while the 3D
structure of the microcapsule behaves physical cues to facilitate cell-cell
interactions.
PMID- 25129776
TI - Polyoxometalates acid treatment for preparing starch nanoparticles.
AB - In this article, a new way of preparing starch-based nanoparticles (SNPs) with
high yields by a polyoxometalates acid treatment is presented. The particle
morphology, mean size and size distribution of the obtained SNPs are
characterized using a dynamic light scattering (DLS) and scanning electron
microscope (SEM). By changing parameters such as temperature, concentration of
polyoxometalates and treating time the size of SNPs can be controlled. In
addition, there are no changes in the structures of the starch granules as
confirmed by IR or (1)H NMR. Freeze-dried SNPs are amorphous as characterized by
wide-angle X-ray diffraction (WXRD).
PMID- 25129777
TI - Influence of both cation and alginate nature on the rheological behavior of
transition metal alginate gels.
AB - The rheological properties of several ionotropic alginate hydrogels were
investigated according to the nature of the divalent cation (Mn(2+), Co(2+),
Cu(2+)) and the guluronic fraction of the alginate (HG and LG for "high G
content" and "low G-content"). Six hydrogels (Mn-LG, Mn-HG, Co-LG, Co-HG, Cu-LG
and Cu-HG) were synthesized and studied by spectromechanical analyses. On one
hand, Cu-HG, Cu-LG and Co-HG behaved as viscoelastic solids: the elastic
contribution was higher than the dissipative component in all the frequency range
studied (G'>G"). No flow zone (G">G') was detected even at very low values of the
shearing frequency. On the other, Mn-HG, Mn-LG and Co-LG presented a
spectromechanical behavior that resembled that observed classically for entangled
polymers. Indeed, at high frequency, these latter materials could be compared to
a viscoelastic solid but at low frequency, the flow zone was described and the
viscous character became prevalent with finite relaxation time. Very good
correlations with the microscopic structurations of the network were evidenced
(rubbery vs. flow zone and fibrillar vs. complex morphology respectively).
PMID- 25129778
TI - Novel polymer Li-ion binder carboxymethyl cellulose derivative enhanced
electrochemical performance for Li-ion batteries.
AB - Novel water-based binder lithium carboxymethyl cellulose (CMC-Li) is synthesized
by cotton as raw material. The mechanism of the CMC-Li as a binder is reported.
Electrochemical properties of batteries' cathodes based on commercially available
lithium iron phosphate (LiFePO4, LFP) and water-soluble binder are investigated.
Sodium carboxymethyl cellulose (CMC-Na, CMC) and CMC-Li are used as the binder.
After 200 cycles, compared with conventional poly(vinylidene fluoride) (PVDF)
binder, the CMC-Li binder significantly improves cycling performance of the LFP
cathode 96.7% of initial reversible capacity achieved at 175 mA h g(-1). Constant
current charge-discharge test results demonstrate that the LFP electrode using
CMC-Li as the binder has the highest rate capability, followed closely by those
using CMC and PVDF binders, respectively. Electrochemical impedance spectroscopy
test results show that the electrode using CMC-Li as the binder has lower charge
transfer resistance than the electrodes using CMC and PVDF as the binders.
PMID- 25129779
TI - Green synthesis of silver and gold nanoparticles employing levan, a biopolymer
from Acetobacter xylinum NCIM 2526, as a reducing agent and capping agent.
AB - With a vision of finding greener materials to synthesize nanoparticles, we report
the production and isolation of levan, a polysaccharide with repeating units of
fructose, from Acetobacter xylinum NCIM2526. The isolated levan were
characterized using potassium ferricyanide reducing power assay, Fourier
transform infra-red (FTIR) spectroscopy and (1)H nuclear magnetic resonance
spectroscopy ((1)H NMR). To exploit levan in nanotechnology, we present a simple
and greener method to synthesize silver nanoparticles (AgNPs) and gold
nanoparticles (AuNPs) using biopolymer, levan as both reducing and stabilizing
agents. The morphology and stability of the AgNPs and AuNPs were examined by
transmission electron microscopy (TEM) and UV-vis absorption (UV-vis)
spectroscopy. The possible capping mechanism of the nanoparticles was postulated
using FTIR studies. As synthesized biogenic nanoparticles showed excellent
catalytic activity as evidenced from sodium borohydride mediated reduction of 4
nitro phenol and methylene blue.
PMID- 25129780
TI - Inter vs. intraglycosidic acetal linkages control sulfation pattern in semi
synthetic chondroitin sulfate.
AB - Microbial-sourced unsulfated chondroitin could be converted into chondroitin
sulfate (CS) polysaccharide by a multi-step strategy relying upon benzylidenation
and acetylation reactions as key-steps for its regioselective protection. By
conducting the two reactions one- or two-pots, CSs with different sulfation
patterns could be obtained at the end of the semi-synthesis. In particular, a CS
polysaccharide possessing sulfate groups randomly distributed between positions 4
and 6 of N-acetyl-galactosamine (GalNAc) units could be obtained through the two
pots route, whereas the one-pot pathway allowed an additional sulfation at
position 3 of some glucuronic acid (GlcA) units. This difference was ascribed to
the stabilization of a labile interglycosidic benzylidene acetal involving
positions O-3 and O-6 of some GlcA and GalNAc, respectively, when the benzylidene
acetylation reactions were conducted in a one-pot fashion. Isolation and
characterization of a polysaccharide intermediate showing interglycosidic acetal
moieties was accomplished.
PMID- 25129781
TI - Dextran synthesized by Leuconostoc mesenteroides BD1710 in tomato juice
supplemented with sucrose.
AB - The characteristics of the growth of Leuconostoc mesenteroides BD1710 and the
synthesis of dextran in tomato juice supplemented with 15% sucrose were assayed.
L. mesenteroides BD1710 could synthesize approximately 32 g L(-1) dextran in the
tomato-juice-sucrose medium when cultured at 28 degrees C for 48 h, which was on
the same level as the dextran yield in a chemically defined medium. The viscosity
of the cultured tomato-juice-sucrose medium with various dextran contents was
also measured. The results of the monosaccharide composition, molecular-weight
distribution, Fourier transform infrared spectra (FTIR) and nuclear magnetic
resonance spectra (NMR) showed that the polysaccharide synthesized by L.
mesenteroides BD1710 in the tomato-juice-sucrose medium was dextran with a peak
molecular weight of 6.35 * 10(5)Da, a linear backbone composed of consecutive
alpha-(1 -> 6)-linked d-glucopyranosyl units and approximately 6% alpha-(1 -> 3)
branches.
PMID- 25129782
TI - In vitro fermentation of the polysaccharides from Cyclocarya paliurus leaves by
human fecal inoculums.
AB - In vitro fermentation of polysaccharide from Cyclocarya paliurus leaves by human
fecal inoculums was investigated by determining the changes in contents of
neutral and reducing sugar and pH value, consumption of monosaccharide and
production of short-chain fatty acids (SCFAs). During fermentation, the content
of neutral sugar and reducing sugar decreased as fermentation time increased
except that the content of reducing sugar increased within the fermentation time
0.5h. The pH value significantly dropped from 7.2 to 6.04. Remarkably, the
greatest yields and the fastest consumption of galacturonic acid were found and
the yield of glucose and arabinose were relatively high. The dominant SCFAs,
which were acetic acid, propionic acid and n-butyric acid, significantly
increased. These results showed that polysaccharide was partly fermented,
glycosidic bonds with galacturonic acid being more susceptible to be attacked by
gut bacteria and galacturonic acid might be deemed as the main producer of acetic
acid.
PMID- 25129783
TI - Hydration and the phase diagram of acid hydrolyzed potato starch.
AB - We investigated hydration of acid hydrolyzed potato starch (maltodextrin)
employing a multi-method approach. In particular, synchrotron radiation X-ray
scattering and differential scanning calorimetry were used, and, for the first
time, the material was investigated with sorption calorimetry and a newly
developed quartz crystal microbalance with humidity scanning. The dry starch was
found to be in an amorphous state. During hydration it exhibits a glass
transition in both bulk and thin film samples, followed by an exothermic event
where the starch crystallized. Recrystallized bulk samples displayed neither a
pronounced glass transition nor crystallization upon hydration whereas both
events occurred in thin film samples. The hydration-driven crystallization
resulted in an X-ray pattern consistent with the coexistence of A and B type
crystallites; however, at higher water concentrations only the B form occurred.
The results were used to construct the first ever acid hydrolyzed starch-water
phase diagram.
PMID- 25129785
TI - Preparation of oxidized agar and characterization of its properties.
AB - A series of oxidized agars with different carboxyl content were prepared, and
their properties were determined and analyzed. The results showed that the
gelling temperature, the optical rotation and the apparent viscosity of the agar
solution, and the melting temperature, the strength, the hardness, the
fracturability, the springiness, the chewiness and the gumminess of agar gel all
decreased except that the cohesiveness increased after oxidation. The gel
skeleton structures of agar before and after oxidation were all of the porous
network structures, but the pores of gel skeleton structure became smaller and
denser after oxidation.
PMID- 25129784
TI - Free-radical degradation by Fe2+/Vc/H2O2 and antioxidant activity of
polysaccharide from Tremella fuciformis.
AB - The free-radical degradation and antioxidant activity of polysaccharide from
Tremella fuciformis was investigated. In present study, the combination of
Fe(2+), ascorbic acid and H2O2 was used as degradation regents in order to obtain
the lower molecular weight product. The result ascertained oxidative-reduce
degradation did not change the main structure of polysaccharides in the test
conditions. Five degraded polysaccharides were selected to evaluate their
antioxidant activities in vitro. It was found that the degraded sample with lower
molecular weight possessed the higher antioxidant activities. It was possible
that free-radical degradation is an effective way for enhancing antioxidant
activity to decrease molecular weight of polysaccharides.
PMID- 25129786
TI - Probing the structural details of xylan degradation by real-time NMR
spectroscopy.
AB - The biodegradation of abundantly available cell wall polysaccharides has recently
received much attention, not least because cell wall polysaccharides are
substrates for the human gut microbiota and for environmentally sustainable
processes of biomass conversion to value-added compounds. A major fraction of
cereal cell wall polysaccharides consists of arabinoxylans. Arabinoxylan and its
degradation products are therefore present in a variety of agro-industrial
residues and products. Here, we undertook to track the structural details of
wheat arabinoxylan degradation with high resolution NMR spectroscopy. More than
15 carbohydrate residues were distinguished in the substrate and more than 20
residues in partially degraded samples without any sample cleanup. The resolution
of a plethora of structural motifs in situ permits the readout of persisting
structures in degradation processes and in products. Reaction progress was
visualized for the biodegradation of arabinoxylan by different crude microbial
enzyme preparations. The direct observation of structural details in complex
mixtures containing arabinoxylan fragments is significant, as such structural
details reportedly modulate the health-promoting functions of arabinoxylan
fragments.
PMID- 25129787
TI - Hydroxyethylcellulose used as an eco-friendly inhibitor for 1018 c-steel
corrosion in 3.5% NaCl solution.
AB - The inhibition effect of hydroxyethylcellulose (HEC) on 1018 c-steel corrosion in
3.5% NaCl solution was investigated by using potentiodynamic polarization,
electrochemical frequency modulation (EFM) and electrochemical impedance
spectroscopy (EIS) techniques. The potentiodynamic polarization studies suggested
that HEC acts as a mixed-type inhibitor. Data obtained from EIS were analyzed to
model the corrosion inhibition process through equivalent circuit. Results
obtained from EFM technique were shown to be in agreement with potentiodynamic
and EIS techniques. The adsorption behavior of HEC on steel surface follows the
Langmuir adsorption isotherm. Thermodynamic parameter (DeltaG degrees (ads)) and
activation parameters (Ea(*), DeltaH(*) and DeltaS(*)) were calculated to
investigate mechanism of inhibition. Scanning electron microscopy (SEM) and
energy dispersive X-ray (EDX) analysis system were performed to characterize the
film formed on the metal surface. DMol(3) quantum chemical calculations were
performed to support the adsorption mechanism with the structure of HEC molecule.
PMID- 25129788
TI - Effect of carboxymethylation on antioxidant properties and radical degradation of
mannans and glucans.
AB - Carboxymethyl derivatives (CM-derivatives) of alpha,beta-mannans from yeasts,
Saccharomyces cerevisiae beta-glucan and dextran (alpha-glucan) were found to
possess strong antioxidant activities against reactive hydroxyl radicals (OH*)
compared to underivatized polysaccharides. When CM-derivatives having similar DS
(0.41-0.45) were compared, the antioxidant activity decreased in order CM
mannan>CM-beta-glucan>CM-dextran. Moreover, the antioxidant activities against
OH* increased with increasing degree of substitution (DS) of polysaccharides. The
CM-mannan and CM-dextran with the highest DS (0.73 and 1.1, respectively) were
the strongest antioxidants and their degradation by OH* decreased with increased
carboxymethylation. The scavenging abilities of CM-polysaccharides against stable
DPPH radical (DPPH) were lower than those of original underivatized ones. Also
this scavenging property against DPPH was lower compared to antioxidant effect
against OH*.
PMID- 25129789
TI - Purification, characterisation and protective effects of polysaccharides from
alfalfa on hepatocytes.
AB - The objective of this study was to determine the preliminary characteristics and
protective effects of alfalfa polysaccharides (APS) on hepatocytes in vitro. The
crude APS was purified by DEAE-cellulose and Sephadex G-100 chromatography,
resulting in the four purified fractions: APS-1, APS-2, APS-3 and APS-4. The
results indicated that APS-3 had higher carbohydrate and uronic acid contents and
that APS-4 had a more complicated monosaccharide composition compared to the
other purified fractions. The average molecular weights of APS-1, APS-2, APS-3
and APS-4 were 48,536, 6,221, 66,559 and 13,076 Da, respectively. Furthermore,
APS (crude and its purified fractions) restored the activities of antioxidant
enzymes and increased the total antioxidant capacity of hepatocytes subjected to
H2O2-induced oxidative stress. Furthermore, APS treatment counteracted the
increases in lactic dehydrogenase and malonaldehyde in the culture supernatant.
These results clearly demonstrate that APS possesses a protective effect against
oxidative injury in hepatocytes.
PMID- 25129790
TI - Effects of carbohydrate sources on biosorption properties of the novel
exopolysaccharides produced by Arthrobacter ps-5.
AB - The crude exopolysaccharides (EPSs) were obtained from Arthrobacter ps-5
fermentation using various carbohydrate sources followed by centrifugation,
ethanol precipitation, and the isolated EPSs were further deproteinized and
lyophilized. Carbohydrates from various sources resulted in different yield of
EPSs from the fermentation and different molecular weight of EPSs. A maximum
yield of 0.27 mg/g was achieved by using the culture medium supplemented with
sucrose. The EPS produced by glucose-supplemented medium had the maximum content
of acidic polysaccharides, subsequently presented the highest biosorption
capacity for Cu(2+) and Pb(2+) at 257.9 mg/g and 331.8 mg/g, respectively. The
ratio of acidic to neutral polysaccharides presented in EPSs was a key factor to
explicate the biosorption mechanism, the higher the ratio, the stronger the
biosorption capacity.
PMID- 25129791
TI - Process optimization and analysis of microwave assisted extraction of pectin from
dragon fruit peel.
AB - Microwave assisted extraction (MAE) technique was employed for the extraction of
pectin from dragon fruit peel. The extracting parameters were optimized by using
four-variable-three-level Box-Behnken design (BBD) coupled with response surface
methodology (RSM). RSM analysis indicated good correspondence between
experimental and predicted values. 3D response surface plots were used to study
the interactive effects of process variables on extraction of pectin. The optimum
extraction conditions for the maximum yield of pectin were power of 400 W,
temperature of 45 degrees C, extracting time of 20 min and solid-liquid ratio of
24 g/mL. Under these conditions, 7.5% of pectin was extracted.
PMID- 25129792
TI - pH sensitive N-succinyl chitosan grafted polyacrylamide hydrogel for oral insulin
delivery.
AB - pH sensitive PAA/S-chitosan hydrogel was prepared using ammonium persulfate (APS)
as an initiator and methylenebisacrylamide (MBA) as a crosslinker for oral
insulin delivery. The synthesized copolymer was characterized by Fourier
transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) study;
morphology was observed under scanning electron microscope (SEM). The PAA/S
chitosan with ~ 38% of insulin loading efficiency (LE) and ~ 76% of insulin
encapsulation efficiency (EE), showed excellent pH sensitivity, retaining ~ 26%
of encapsulated insulin in acidic stomach pH 1.2 and releasing of ~ 98% of
insulin in the intestine (pH 7.4), providing a prolonged attachment with the
intestinal tissue. The oral administration of insulin loaded PAA/S-chitosan
hydrogel was successful in lowering the blood glucose level of diabetic mice. The
bioavailability of insulin was ~ 4.43%. Furthermore, no lethality or toxicity was
documented after its peroral administration. Thus, PAA/S-chitosan hydrogel could
serve as a promising oral insulin carrier in future.
PMID- 25129793
TI - Molecular engineering of manipulated alginate-based polyurethanes.
AB - The novel soluble alginate-based polyurethanes in organic solvents were
synthesized by the reaction of NCO-terminated prepolymers and tributylammonium
alginate (TBA-Alg) for the first time. The chemical structures of synthesized
polyurethanes were characterized using FTIR, (1)H NMR and TGA. The reaction
completion was confirmed by disappearing of NCO band in FTIR spectra.
Furthermore, a peak at 4.71 ppm and some small peaks at a range of 4.12-4.37 ppm
in the (1)H NMR of alginate-based polyurethanes were assigned to the backbone of
alginate. The results of both FTIR and (1)H NMR were remarkably confirmed by TGA
data. The ionic nature of polyurethane backbone not only affects on thermal
properties of samples, but it also changes the chemically-bonded alginate
morphology. Both polyether and polyester based non-ionic polyurethanes extended
by TBA-Alg illustrated the distinct alginate, whereas those ionomers extended by
alginate were appeared as the continuous systems at nanoscale.
PMID- 25129794
TI - Enzymatic hydrolysis studies of arabinogalactan-protein structure from Acacia
gum: the self-similarity hypothesis of assembly from a common building block.
AB - Arabinogalactan (AG) and arabinogalactan-protein (AGP) fractions were treated
enzymatically using several proteases in acidic (pH 4) and alkaline (pH 7)
conditions in order to go deeper insight into the structure and conformations of
the two main fractions of Acacia senegal gum. Endoproteinase Glu-C, pepsin and
phosphatase acid were thus used in acidic conditions while subtilisin A, pronase,
trypsin, papain and proteinase K were used in alkaline conditions to cleave
protein moieties of the two fractions. Structures of AG and AGP were probed using
HPSEC-MALLS, small angle neutron scattering and far-UV circular dichroism.
Enzymes did not affect AG fraction structure whatever the pH conditions used,
highlighting the inaccessibility of the peptide backbone and the remarkable
stability of this fraction in acidic and alkaline conditions. This result was in
agreement with the thin oblate ellipsoid model we previously identified for the
AG fraction where the 43 amino-acid residues peptide sequence was supposed, based
on spectroscopic methods, to be totally buried. Contrary to AG fraction, AGP
protein component was therefore cleaved using enzymes in alkaline conditions, the
absence of enzymatic efficiency in acidic conditions being probably ascribed to
long range electrostatic repulsions occurring between negatively charged AGP and
enzymes at pH 4. The decrease of AGP molecular weight after hydrolysis in
alkaline conditions went from 1.79 * 10(6) g mol(-1) for control AGP to as low as
1.68 * 10(5) g mol(-1) for papain-treated AGP. The overall structure of the
enzyme-treated AGPs was found to be surprisingly quite similar whatever the
enzyme used and close, with however some subtle differences, to AG unit. A tri
axial ellipsoid conformation was found in enzyme-treated AGPs and the two main
preferential distances identified in the pair distance distribution function
would claim in favor of rod-like or elongated particles or alternatively would
indicate the presence of two particles differing in dimensions. The secondary
structures content of control and enzyme-treated AGPs were similar, highlighting
both the high rigidity of the protein backbone and the overall symmetry of AGP.
This conclusion was reinforced by the more compact structures found when AGP was
intact compare to the more elongated structures found when AGP was enzymatically
cleaved. Finally, the structural similarities found in enzyme-treated AGP
together with the theoretical calculations to analytically probe the type of
branching would suggest that AGP would be made of a self-similar assembly of two
types of building blocks, the second being a five-fold repetition of the first
one, for which palindromic amino acid sequence would ensure a self-ordering of
carbohydrate moieties along the polypeptide chains. The cleavage would therefore
lead to hydrolysed building blocks with similar secondary structures and
conformations whatever the enzyme used.
PMID- 25129795
TI - Synthesis of alginate bioencapsulated nano-hydroxyapatite composite for selective
fluoride sorption.
AB - This article focuses on the development of eco-friendly adsorbent by alginate
(Alg) bioencapsulating nano-hydroxyapatite (n-HAp) namely n-HApAlg composite for
defluoridation studies in batch mode. n-HAp powder utilized as a promising
defluoridating material, but it causes a significant pressure drop during field
applications. To overcome such technological bottlenecks, n-HApAlg composite was
synthesized. The defluoridation capacity (DC) of synthesized n-HApAlg composite
possesses an enhanced DC of 3870 mg F(-)/kg when compared to n-HAp and calcium
alginate (CaAlg) composite which possess DC of 1296 and 680 mg F(-)/kg,
respectively. The biocomposite features were characterized using FTIR and SEM
with EDAX analysis. The various adsorption influencing parameters like contact
time, pH, co-anions, initial fluoride concentration and temperature were
optimized. The adsorption process was enlightened by various isotherms and
kinetic models. The suitability of the biocomposite at field conditions was also
tested.
PMID- 25129796
TI - Nanoporous membranes with cellulose nanocrystals as functional entity in
chitosan: removal of dyes from water.
AB - Fully biobased composite membranes for water purification were fabricated with
cellulose nanocrystals (CNCs) as functional entities in chitosan matrix via
freeze-drying process followed by compacting. The chitosan (10 wt%) bound the
CNCs in a stable and nanoporous membrane structure with thickness of 250-270 MUm,
which was further stabilized by cross-linking with gluteraldehyde vapors.
Scanning electron microscopy (SEM) studies revealed well-individualized CNCs
embedded in a matrix of chitosan. Brunauer, Emmett and Teller (BET) measurements
showed that the membranes were nanoporous with pores in the range of 13-10nm. In
spite of the low water flux (64 Lm(-2) h(-1)), the membranes successfully removed
98%, 84% and 70% respectively of positively charged dyes like Victoria Blue 2B,
Methyl Violet 2B and Rhodamine 6G, after a contact time of 24h. The removal of
dyes was expected to be driven by the electrostatic attraction between negatively
charged CNCs and the positively charged dyes.
PMID- 25129797
TI - Horse chestnut (Aesculus hippocastanum L.) starch: Basic physico-chemical
characteristics and use as thermoplastic material.
AB - Starch isolated from non-edible Aesculus hippocastanum seeds was characterized
and used for preparing starch-based materials. The apparent amylose content of
the isolated starch was 33.1%. The size of starch granules ranged from 0.7 to 35
MUm, and correlated with the shape of granules (spherical, oval and irregular).
The chain length distribution profile of amylopectin showed two peaks, at
polymerization degree (DP) of 12 and 41-43. Around 53% of branch unit chains had
DP in the range of 11-20. A. hippocastanum starch displayed a typical C-type
pattern and the maximum decomposition temperature was 317 degrees C.
Thermoplastic starch (TPS) prepared from A. hippocastanum with glycerol and
processed by melt blending exhibited adequate mechanical and thermal properties.
In contrast, plasticized TPS with glycerol:malic acid (1:1) showed lower thermal
stability and a pasty and sticky behavior, indicating that malic acid accelerates
degradation of starch during processing.
PMID- 25129798
TI - Salt stress alters the cell wall polysaccharides and anatomy of coffee (Coffea
arabica L.) leaf cells.
AB - Coffea arabica is the most important agricultural commodity in the world, and
salinity is a major threat to its sustainable irrigation. Coffee leaf
polysaccharides from plants subjected to salt stress were extracted and the
leaves visualized through optical and electron microscopy. Alterations were
detected in the monosaccharide composition of the pectin and hemicelluloses, with
increases in uronic acid in all fractions. Changes in the polysaccharides were
confirmed by HPSEC and FTIR. Moreover, the monolignol content was increased in
the final residue, which suggests increased lignin content. The cytoplasm was
altered, and the chloroplasts appeared irregular in shape. The arrangement of the
stroma lamellae was disordered, and no starch granules were present. It was
concluded that leaves of C. arabica under salt stress showed alterations in cell
wall polysaccharides, increased monolignol content and structural damage to the
cells of the mesophyll.
PMID- 25129799
TI - Preparation and stabilization of D-limonene Pickering emulsions by cellulose
nanocrystals.
AB - The aim of this study was to investigate D-limonene Pickering emulsion stabilized
by cellulose nanocrystals (CNCs) and factors that may affect its properties. CNCs
were prepared by ammonium persulfate hydrolysis of corncob cellulose, and D
limonene Pickering emulsions were generated by ultrasonic homogenizing method.
The morphology and size of the prepared emulsions with different CNCs
concentrations were studied by optical microscopy and laser light diffraction. In
addition, factors that may affect the stability of emulsions such as ionic
concentration, pH and temperature were also studied. As indicated by the
experiment data, when temperature rose, the stability to of emulsions would be
increased, and the stability of emulsions was reduced with low pH or high salt
concentration due to electrostatic screening of the negatively charged CNC
particles. In conclusion, high stability of D-limonene Pickering emulsions could
be obtained by CNCs.
PMID- 25129800
TI - Isolation, structural characterization, and potential applications of
hemicelluloses from bamboo: a review.
AB - Bamboo is one of the mostly fast growing natural resources and has great
potential to be used as a valuable feedstock for biorefinery. The hemicelluloses,
next to cellulose, represent a diverse group of polysaccharides in plant cell
wall. Elucidation and understanding of the hemicelluloses from bamboo play an
important role in the efficient conversion of bamboo into biofuels and
bioproducts. This review summarized the recent reports on hemicelluloses from
bamboo, including immunohistochemical localization, focused on extraction and
purification methods, chemical components, characterization of structural
features, as well as physicochemical properties. In addition, attention was also
paid to derivatives prepared from bamboo hemicelluloses and to potential
applications of bamboo hemicelluloses in a variety of areas such as biomaterials,
biofuel, and food.
PMID- 25129801
TI - Thermal degradation and stability of cationic starches and their complexes with
iodine.
AB - Thermal degradation processes of cationic starch (CS) and CS-iodine complex were
investigated by thermogravimetry (TG) in air and under nitrogen atmosphere at 10
degrees C min(-1) heating rate and compared. Moreover, the thermal stability of
CS with different degree of substitution (DS) and their complexes with iodine was
studied by TG under nitrogen atmosphere at different heating rates. The average
E(a) values for CS were found to be slightly lower as compared to native starch,
suggesting lower thermal stability of modified starches due to cationisation. The
main thermodegradation event of native starch-iodine and CS-iodine complexes can
be separated in two steps: the release of iodine in the range of 137-196 degrees
C, followed by the subsequent iodine induced thermochemical degradation of
polysaccharide macromolecules, which appears at lower temperatures than in the
absence of iodine. "Blue" inclusion complex showed higher thermal stability than
ionic CS-iodine complex.
PMID- 25129802
TI - Impact of molecular and crystalline structures on in vitro digestibility of waxy
rice starches.
AB - The in vitro digestibility, molecular structure and crystalline structure of waxy
rice starches isolated from six Korean cultivars (Shinsun, Dongjin, Baekok,
Whasun, Chungbaek, and Bosuk) were investigated. The molecular weight (M(w)) of
waxy rice starches ranged from 1.1 * 10(8)g/mol to 2.2 * 10(8)g/mol. Chungbaek
waxy rice starch had the highest average chain length (24.3) and proportion
(20.7%) of long branch chains (DP >= 37), and the lowest proportion (19.0%) of
short branch chains (DP 6-12) among the tested six waxy rice starches. The
relative crystallinity and intensity ratio of 1047/1022 ranged from 38.9% to
41.1% and from 0.691 to 0.707, respectively. Chungbaek had the highest
gelatinization temperature and enthalpy. Chungbaek had the highest pasting
temperature (70.7 degrees C), setback (324 cP) and final viscosity (943 cP),
whereas Baekok showed the highest peak viscosity (1576 cP) and breakdown (1031
cP). Chungbaek had lower rapidly digestible starch (RDS) content and expected
glycemic index (eGI), and higher resistant starch (RS) content, whereas Whasun
exhibited higher RDS content and eGI. The slowly digestible starch (SDS) content
of Shinsun (38.3%) and Bokok (32.0%) was significantly higher than that of other
cultivars (11.3-22.0%).
PMID- 25129803
TI - Synthesis of chitosan-PEO hydrogels via mesylation and regioselective Cu(I)
catalyzed cycloaddition.
AB - In this work, a well-defined hydrogel was developed by coupling chitosan with PEO
through "click chemistry". Azide functionalities were introduced onto chitosan,
through mesylation of C-6 hydroxyl groups, and reacted with a di-alkyne PEO by a
regioselective Cu(I)-catalyzed cycloaddition. This synthetic approach allowed us
to obtain a hydrogel with a controlled crosslinking degree. In fact, the extent
of coupling is strictly dependent on the amount of azido groups on chitosan,
which in turn can be easily modulated. The obtained hydrogel, with a crosslinking
degree of around 90%, showed interesting swelling properties. With respect to
chitosan hydrogels reported in literature, a considerably higher equilibrium
uptake was reached (940%). The possibility to control the crosslinking degree of
hydrogel and its capability to rapidly absorb high amounts of water make this
material suitable for several applications, such as controlled drug release and
wound healing.
PMID- 25129804
TI - Redox-stimuli responsive micelles from DOX-encapsulating polycaprolactone-g
chitosan oligosaccharide.
AB - Chitosan-based amphiphilic graft copolymers are commonly obtained by modification
of chitosan backbones with synthetic polymers hampering both bioactivity and
biodegradability. In this work, we report the preparation of a series of chitosan
oligosaccharide-grafted copolymers (PCL-g-COs) from coupling reactions between
azide-pendent polycaprolactones (PCL-N3) and reducing-end alkynyl-modified
chitosan oligosaccharides (COs-alkynyl). The resulting PCL-g-COs self-organized
in water into nanoscale micelles (Rh<20 nm) having a COs shell and a PCL core.
Locking of the core-micelles structure employing a disulfide-containing bis
alkyne cross-linker resulted in the formation of nano-vehicles which can be
degraded in response to physiological (redox) stimuli. This feature was
advantageously exploited to preferentially release an anticancer drug,
doxororubicin, in response to the intracellular glutathione level.
PMID- 25129805
TI - Rheological study of chitosan acetate solutions containing chitin nanofibrils.
AB - Rheological properties of chitosan acetate solutions containing chitin
nanofibrils (n-chitin) and biocompatible plasticizers intended for preparation of
biodegradable films are reported in the steady, oscillatory and transient shear
flow. The experiments were performed on slurries with an optimum proportion of
65/35 wt.% between chitosan and n-chitin in the films which was determined from
our results of mechanical properties and absorption of water vapor. The time
dependent dynamic experiments revealed the chitin nanofibrils as an effective
"gelling agent" of chitosan phase. The phenomenon is explained by a chitosan-like
surface of n-chitin and by the interactions inducing orientational cooperativity
of chitosan molecules dissolved in close neighborhood of the anisotropic chitin
nanofibrils. Additions of glycerol or poly(ethylene glycol), improving mechanical
properties of the films, delay significantly the onset of gelation of chitosan/n
chitin slurries. The effect is induced by an increase in viscosity of the
slurries and by their enhanced chaotropic character.
PMID- 25129806
TI - Influence of feeding regimens on rat gut fluids and colonic metabolism of
diclofenac-beta-cyclodextrin.
AB - Feeding states may affect the performance of colonic prodrugs. The aim is to
investigate the influence of feeding regimen in Wistar rats on: (i) distribution
and pH contents along the gut and (ii) metabolism of two colonic prodrugs,
diclofenac-beta-cyclodextrin and a commercially available control, sulfasalazine,
within the caecal and colonic contents. Male Wistar rats were subject to four
different feeding regimens, the gut contents characterized (mass and pH) and the
metabolism of prodrugs investigated. The feeding regimen affects gut contents
(mass and pH), more specifically in the stomach and lower intestine, and affects
the rate of metabolism of diclofenac-beta-cyclodextrin, but not that of
sulfasalazine. The latter's degradation is much faster than that of diclofenac
beta-cyclodextrin while the metabolism of both prodrugs is faster in colonic
(versus caecal) contents. Fasting results in most rapid degradation of diclofenac
beta-cyclodextrin, possibly due to lack of competition (absence of food) for
microbial enzymatic activity.
PMID- 25129807
TI - Desipramine and citalopram attenuate pretest swim-induced increases in
prodynorphin immunoreactivity in the dorsal bed nucleus of the stria terminalis
and the lateral division of the central nucleus of the amygdala in the forced
swimming test.
AB - Dynorphin in the nucleus accumbens shell plays an important role in
antidepressant-like effect in the forced swimming test (FST), but it is unclear
whether desipramine and citalopram treatments alter prodynorphin levels in other
brain areas. To explore this possibility, we injected mice with desipramine and
citalopram 0.5, 19, and 23 h after a 15-min pretest swim and observed changes in
prodynorphin expression before the test swim, which was conducted 24 h after the
pretest swim. The pretest swim increased prodynorphin immunoreactivity in the
dorsal bed nucleus of the stria terminalis (dBNST) and lateral division of the
central nucleus of the amygdala (CeL). This increase in prodynorphin
immunoreactivity in the dBNST and CeL was blocked by desipramine and citalopram
treatments. Similar changes in prodynorphin mRNA levels were observed in the
dBNST and CeL, but these changes did not reach significance. To understand the
underlying mechanism, we assessed changes in phosphorylated CREB at Ser(133)
(pCREB) immunoreactivity in the dBNST and central nucleus of the amygdala (CeA).
Treatment with citalopram but not desipramine after the pretest swim
significantly increased pCREB immunoreactivity only in the dBNST. These results
suggest that regulation of prodynorphin in the dBNST and CeL before the test swim
may be involved in the antidepressant-like effect of desipramine and citalopram
in the FST and suggest that changes in pCREB immunoreactivity in these areas may
not play an important role in the regulation of prodynorphin in the dBNST and
CeA.
PMID- 25129808
TI - Enhancing the efficiency of direct reprogramming of human primary fibroblasts
into dopaminergic neuron-like cells through p53 suppression.
AB - Dopaminergic (DA) neuron-like cells obtained through direct reprogramming of
primary human fibroblasts offer exciting opportunities for treatment of
Parkinson's disease. A significant obstacle is the low efficiency of conversion
during the reprogramming process. Here, we demonstrate that the suppression of
p53 significantly enhances the efficiency of transcription factor-mediated
conversion of human fibroblasts into functional dopaminergic neurons. In
particular, blocking p53 activity using a dominant-negative p53 (p53-DN) in IMR90
cells increases the conversion efficiency by 5-20 fold. The induced DA neuron
like cells exhibit dopamine neuron-specific gene expression, significant dopamine
uptake and production capacities, and enables symptomatic relief in a rat
Parkinson's disease model. Taken together, our findings suggest that p53 is a
critical barrier in direct reprogramming of fibroblast into dopaminergic neurons.
PMID- 25129809
TI - No correlation between the diversity and productivity of assemblages: evidence
from the phytophage and predator assemblages in various cotton agroecosystems.
AB - Biodiversity research has shown that primary productivity increases with plant
species number, especially in many experimental grassland systems. Here, we
assessed the correlation between productivity and diversity of phytophages and
natural enemy assemblages associated with planting date and intercropping in four
cotton agroecosystems. Twenty-one pairs of data were used to determine Pearson
correlations between species richness, total number of individuals, diversity
indices and productivity for each assemblage every five days from 5 June to 15
September 2012. At the same trophic level, the productivity exhibited a
significant positive correlation with species richness of the phytophage or
predator assemblage. A significant correlation was found between productivity and
total number of individuals in most cotton fields. However, no significant
correlations were observed between productivity and diversity indices (including
indices of energy flow diversity and numerical diversity) in most cotton fields
for either the phytophage or the predator assemblages. Species richness of
phytophage assemblage and total individual numbers were significantly correlated
with primary productivity. Also, species richness of natural enemy assemblage and
total number of individuals correlated with phytophage assemblage productivity. A
negative but not significant correlation occurred between the indices of
numerical diversity and energy flow diversity and lower trophic-level
productivity in the cotton-phytophage and phytophage-predator assemblages for
most intercropped cotton agroecosystems. Our results clearly showed that there
were no correlations between diversity indices and productivity within the same
or lower trophic levels within the phytophage and predator assemblages in cotton
agroecosystems, and inter-cropped cotton fields had a stronger ability to support
the natural enemy assemblage and potentially to reduce phytophages.
PMID- 25129810
TI - False memories to emotional stimuli are not equally affected in right- and left
brain-damaged stroke patients.
AB - Previous research has attributed to the right hemisphere (RH) a key role in
eliciting false memories to visual emotional stimuli. These results have been
explained in terms of two right-hemisphere properties: (i) that emotional stimuli
are preferentially processed in the RH and (ii) that visual stimuli are
represented more coarsely in the RH. According to this account, false emotional
memories are preferentially produced in the RH because emotional stimuli are both
more strongly and more diffusely activated during encoding, leaving a memory
trace that can be erroneously reactivated by similar but unstudied emotional
items at test. If this right-hemisphere hypothesis is correct, then RH damage
should result in a reduction in false memories to emotional stimuli relative to
left-hemisphere lesions. To investigate this possibility, groups of right-brain
damaged (RBD, N=15), left-brain-damaged (LBD, N=15) and healthy (HC, N=30)
participants took part in a recognition memory experiment with emotional
(negative and positive) and non-emotional pictures. False memories were
operationalized as incorrect responses to unstudied pictures that were similar to
studied ones. Both RBD and LBD participants showed similar reductions in false
memories for negative pictures relative to controls. For positive pictures,
however, false memories were reduced only in RBD patients. The results provide
only partial support for the right-hemisphere hypothesis and suggest that inter
hemispheric cooperation models may be necessary to fully account for false
emotional memories.
PMID- 25129811
TI - Combination effects of baicalein with antibiotics against oral pathogens.
AB - BACKGROUND: Baicalein is one of the major flavonoids in Scutellaria baicalensis
Georgi, which has long been used in Asia as herbal medicine. Several biological
effects of baicalein, such as antiviral, anti-inflammatiom, anti-hepatotoxicity,
and anti-tumour properties, have been reported. OBJECTIVE AND DESIGN: In this
study, the antibacterial activities of baicalein were investigated in combination
with ampicillin and/or gentamicin against oral bacteria. RESULTS: Baicalein was
determined with MIC and MBC values ranging from 80 to 320 and 160 to 640 MUg/mL
against oral bacteria. The range of MIC50 and MIC90 were 20-160 MUg/mL and 80-320
MUg/mL, respectively. The combination effects of baicalein with antibiotics were
synergistic (FIC index <0.375-0.5 and FBCI <0.5) against oral bacteria.
Furthermore, a time-kill study showed that the growth of the tested bacteria was
completely attenuated after 1-6 h of treatment with the MIC50 of baicalein,
regardless of whether it was administered alone or with ampicillin or gentamicin.
CONCLUSION: These results suggest that baicalein combined with other antibiotics
may be microbiologically beneficial and not antagonistic.
PMID- 25129812
TI - Effect of radiotherapy on the eruption rate and morphology of the odontogenic
region of rat incisors.
AB - OBJECTIVE: The goal in this study was to evaluate the results of doses of 5 and
15 Gy of radiation in odontogenic region of the rats inferior mandibular-incisors
by a histological analysis and the rate of eruptions. DESIGN: Animals were
divided into three groups: control, radiotherapy 5 Gy and radiotherapy 15 Gy. In
which tooth-eruption-rate was measured every two days. RESULTS: Animals in Group
5 Gy presented values similar to those of the control group. Animals in Group 15
Gy presented reduction in tooth-eruption-rate as of the sixth day of the
experiment, vast disorganization of odontoblasts and ameloblasts, apparent
reduction in cell population in the follicle region and alterations in cervical
loop formation of the dental organ. CONCLUSIONS: It was concluded that there was
a difference between the researched doses, and histological alteration at 15 Gy
lead to statistical reduction in tooth-eruption-rate.
PMID- 25129813
TI - Metal splinter ejected by circular saw into the left ventricle.
AB - We report a case of a metal splinter ejected by a circular saw tooth from a
wooden board into the left ventricle of the heart. A 35-year old man was admitted
second day after accident attributed to work complaining about general weakness.
Only a small non-bleeding wound was found near his sternum. CT scan showed a
metal wire entrapped inside his heart. Successful removal was done during
surgery.
PMID- 25129814
TI - What is the value of topical cooling as an adjunct to myocardial protection?
AB - A best evidence topic in cardiac surgery was written according to a structured
protocol. The question addressed was 'What is the value of topical cooling as an
adjunct to myocardial protection?' Using the reported search, 9 papers
represented the best evidence to answer the clinical question. The authors,
journal, date and country of publication, patient group studied, study type,
relevant outcomes and results of these papers are tabulated. The studies included
four randomized controlled trials (RCTs). Two RCTs demonstrated no
cardioprotective effects of topical hypothermia as they found no statistically
significant differences in myocardial markers between patients with or without
topical cooling. In a randomized study of 249 patients undergoing elective
cardiac surgery, phrenic nerve injury and failure of extubation occurred more
frequently with the use of topical hypothermia with iced slush (P = 0.009 and P =
0.034, respectively). One retrospective analysis found that patients who received
iced topical hypothermia had longer postoperative hospitalization, higher
incidence of atelectasis and higher left diaphragms on chest X-ray. Another study
showed increased morbidity and mortality associated with postoperative
diaphragmatic dysfunction resulting from the use of iced slush topical cooling of
the heart. We conclude that topical cooling is an unnecessary adjunct to
myocardial protection in patients undergoing cardiac surgery. There is no
evidence of any additional cardioprotective benefit. Several studies showed that
the use of topical hypothermia is associated with phrenic nerve injury, leading
to diaphragmatic paralysis and increased pulmonary complications. Moreover, long
term follow-up data showed often incomplete regression of the phrenic nerve
paralysis. However, few randomized studies exist on the value of topical cooling
as an adjunct to myocardial protection.
PMID- 25129815
TI - Motivational interviewing in permanent supportive housing: the role of
organizational culture.
AB - This study evaluated motivational interviewing (MI) in a permanent supportive
housing agency. The agency's contradictory social service and business missions
resulted in an incompatible organizational culture theorized to diminish MI's
effectiveness. A combination of observational, interview, and archival data
collected over 3 years were used to examine MI implementation within an
incompatible supportive housing agency. Two major themes arose: how MI is used to
categorize and change clients in permanent supportive housing and how worker
worker relationships affect MI implementation. The results suggest that within
incompatible organizational environments, key elements of effective MI
implementation are greatly weakened.
PMID- 25129816
TI - Phases and phase transition in insoluble and adsorbed monolayers of amide
amphiphiles: Specific characteristics of the condensed phases.
AB - For understanding the role of amide containing amphiphiles in inherently complex
biological processes, monolayers at the air-water interface are used as simple
biomimetic model systems. The specific characteristics of the condensed phases
and phase transition in insoluble and adsorbed monolayers of amide amphiphiles
are surveyed to highlight the effect of the chemical structure of the amide
amphiphiles on the interfacial interactions in model monolayers. The mesoscopic
topography and/or two-dimensional lattice structures of selected amino acid
amphiphiles, amphiphilic N-alkylaldonamide, amide amphiphiles with specific
tailored headgroups, such as amide amphiphiles based on derivatized ethanolamine,
e.g. acylethanolamines (NAEs) and N-,O-diacylethanolamines (DAEs) are presented.
Special attention is devoted the dominance of N,O-diacylated ethanolamine in
mixed amphiphilic acid amide monolayers. The evidence that a first order phase
transition can occur in adsorption layers and that condensed phase domains of
mesoscopic scale can be formed in adsorption layers was first obtained on the
basis of the experimental characteristics of a tailored amide amphiphile. New
thermodynamic and kinetic concepts for the theoretical description of the
characteristics of amide amphiphile's monolayers were developed. In particular,
the equation of state for Langmuir monolayers generalized for the case that one,
two or more phase transitions occur, and the new theory for phase transition in
adsorbed monolayers are experimentally confirmed at first by amide amphiphile
monolayers. Despite the significant progress made towards the understanding the
model systems, these model studies are still limited to transfer the gained
knowledge to biological systems where the fundamental physical principles are
operative in the same way. The study of biomimetic systems, as described in this
review, is only a first step in this direction.
PMID- 25129817
TI - Hard scalp lump with headache.
PMID- 25129819
TI - Malnutrition among cognitively intact, noncritically ill older adults in the
emergency department.
AB - STUDY OBJECTIVE: We estimate the prevalence of malnutrition among older patients
presenting to an emergency department (ED) in the southeastern United States and
identify subgroups at increased risk. METHODS: We conducted a cross-sectional
study with random time block sampling of cognitively intact patients aged 65
years and older. Nutrition was assessed with the Mini Nutritional Assessment
Short-Form (0 to 14 scale), with malnutrition defined as a score of 7 or less and
at risk for malnutrition defined as a score of 8 to 11. The presence of
depressive symptoms was defined as a Center for Epidemiological Studies
Depression-10 score of 4 or more (0 to 10 scale). RESULTS: Among 138 older
adults, 16% (95% confidence interval [CI] 11% to 23%) were malnourished and 60%
(95% CI 52% to 68%) were either malnourished or at risk for malnutrition.
Seventeen of the 22 malnourished patients (77%) denied previously receiving a
diagnosis of malnutrition. The prevalence of malnutrition was not appreciably
different between men and women, across levels of patient education, or between
those living in urban and rural areas. However, the prevalence of malnutrition
was higher among patients with depressive symptoms (52%), those residing in
assisted living (44%), those with difficulty eating (38%), and those reporting
difficulty buying groceries (33%). CONCLUSION: Among a random sample of
cognitively intact older ED patients, more than half were malnourished or at risk
for malnutrition, and the majority of malnourished patients had not previously
received a diagnosis. Higher rates of malnutrition among individuals with
depression, difficulty eating, and difficulty buying groceries suggest the need
to explore multifaceted interventions.
PMID- 25129820
TI - Efficacy and safety of out-of-hospital intravenous metoprolol administration in
anterior ST-segment elevation acute myocardial infarction: insights from the
METOCARD-CNIC trial.
AB - STUDY OBJECTIVE: We seek to examine the efficacy and safety of prereperfusion
emergency medical services (EMS)-administered intravenous metoprolol in anterior
ST-segment elevation myocardial infarction patients undergoing eventual primary
angioplasty. METHODS: This is a prespecified subgroup analysis of the Effect of
Metoprolol in Cardioprotection During an Acute Myocardial Infarction trial
population, who all eventually received oral metoprolol within 12 to 24 hours. We
studied patients receiving intravenous metoprolol by EMS and compared them with
others treated by EMS but not receiving intravenous metoprolol. Outcomes included
infarct size and left ventricular ejection fraction on cardiac magnetic resonance
imaging at 1 week, and safety by measuring the incidence of the predefined
combined endpoint (composite of death, malignant ventricular arrhythmias,
advanced atrioventricular block, cardiogenic shock, or reinfarction) within the
first 24 hours. RESULTS: From the total population of the trial (N=270), 147
patients (54%) were recruited during out-of-hospital assistance and transferred
to the primary angioplasty center (74 intravenous metoprolol and 73 controls).
Infarct size was smaller in patients receiving intravenous metoprolol compared
with controls (23.4 [SD 15.0] versus 34.0 [SD 23.7] g; adjusted difference -11.4;
95% confidence interval [CI] -18.6 to -4.3). Left ventricular ejection fraction
was higher in the intravenous metoprolol group (48.1% [SD 8.4%] versus 43.1% [SD
10.2%]; adjusted difference 5.0; 95% CI 1.6 to 8.4). Metoprolol administration
did not increase the incidence of the prespecified safety combined endpoint: 6.8%
versus 17.8% in controls (risk difference -11.1; 95% CI -21.5 to -0.6).
CONCLUSION: Out-of-hospital administration of intravenous metoprolol by EMS
within 4.5 hours of symptom onset in our subjects reduced infarct size and
improved left ventricular ejection fraction with no excess of adverse events
during the first 24 hours.
PMID- 25129822
TI - Cellular domains and viral lineages.
AB - It has been claimed that giant DNA viruses represent a separate, fourth domain of
life in addition to the domains of Bacteria, Archaea, and Eukarya. Such
classification disregards fundamental differences between the two types of living
entities - viruses and cells - and results in confusion and controversies in
evolutionary scenarios. We highlight these problems and emphasize the importance
of restricting the term 'domain' to the descendants of the last universal
cellular ancestor (LUCA), based on the shared ribosome structure. We suggest
tracing phylogeny of viruses along evolutionary lineages primarily defined by
virion architectures and the structures of the major capsid proteins.
PMID- 25129821
TI - DJ-1: a promising marker in metastatic uveal melanoma.
AB - PURPOSE: Overexpression of DJ-1 was associated with metastatic uveal melanoma
(UM). The purpose of this study was to evaluate the potential of serum DJ-1 as a
biomarker for metastasis of uveal melanoma. METHODS: Serum DJ-1 levels were
determined by ELISA assays in 27 patients with metastatic UM metastatic uveal
melanoma and in 76 patients who were disease free for at least 10 years and 30
age- and sex-matched controls. Receiver operating characteristic (ROC) curve was
used to evaluate the feasibility of DJ-1 in detection of metastatic uveal
melanoma. RESULTS: Serum DJ-1 levels were significantly higher in patients with
metastatic UM compared with patients who were disease free for at least 10 years
(P < 0.001) or with controls (P < 0.001). ROC curve for DJ-1 revealed an area
under the curve of 86.3%, and when 3.350 ng/mL was used as the cutoff value, a
sensitivity of 74.1% and a specificity of 94.3% were achieved. Comparison of DJ-1
and liver function tests (LFTs) ROC curves indicated that DJ-1 was superior to
LFTs in detection of metastatic UM. CONCLUSIONS: Our data suggest that DJ-1 might
be a promising serum marker for monitoring metastatic uveal melanoma.
PMID- 25129823
TI - Microbial communities associated with human decomposition and their potential use
as postmortem clocks.
AB - Most forensic research that is used to better understand how to estimate the
postmortem interval (PMI) entails the study of the physiochemical characteristics
of decomposition and the effects that environmental factors have on the
decomposition process. Forensic entomology exploits the life cycles of arthropods
like Diptera (blow flies or flesh flies) and Coleoptera (beetles) deposited on
the decaying carcass to determine PMI. Forensic taphonomy, from the Greek word
taphos meaning burial, studies the creation of the fossils of decomposed cadavers
to ascertain information as to the nature and time of death. Compared to other
areas of taphonomy, there have been relatively few forensic science studies that
have investigated the impact of human decomposition on the microbial changes
occurring on or in a corpse or in the soil communities underneath a body. Such
research may facilitate the critical determination of PMI. Therefore, the scope
of this review is to provide a concise summary of the current progress in the
newly emerging field of microbial diversity and the next-generation metagenomic
sequencing approaches for assessing these communities in humans and in the soil
beneath decomposing human.
PMID- 25129824
TI - Motivational Profiles of Gambling Behavior: Self-determination Theory, Gambling
Motives, and Gambling Behavior.
AB - Gambling among young adults occurs at a higher rate than in the general
population and is associated with a host of negative consequences. Self
determination theory (SDT) posits that individuals develop general motivational
orientations which predict a range of behavioral outcomes. An autonomy
orientation portrays a choiceful perspective facilitating personal growth,
whereas a controlled orientation represents a chronic proclivity toward external
pressures and a general lack of choice. Further, an impersonal orientation is
characterized by alack of intention and feeling despondent and ineffective.
Controlled orientation has previously been associated with more frequent and
problematic gambling. This research was designed to examine gambling motives as
mediators of associations between motivational orientations and gambling
behaviors. Undergraduates (N = 252) who met 2+ criteria on the South Oaks
Gambling Screen participated in a laboratory survey assessing their motivational
orientations, gambling motives, and gambling behavior (quantity, frequency, and
problems). Mediation analyses suggested that autonomy was negatively associated
with gambling problems through lower levels of chasing and escape motives.
Further, controlled orientation was associated with more problems through higher
levels of chasing and interest motives. Finally, impersonal orientation was
negatively associated with amount won through escape motives. Overall, results
support exploring gambling behavior and motives using a SDT framework.
PMID- 25129825
TI - Magnetic resonance perfusion and diffusion imaging characteristics of transient
bone marrow edema, avascular necrosis and subchondral insufficiency fractures of
the proximal femur.
AB - PURPOSE: To evaluate magnetic resonance (MR) perfusion and diffusion imaging
characteristics in patients with transient bone marrow edema (TBME), avascular
necrosis (AVN), or subchondral insufficiency fractures (SIF) of the proximal
femur. MATERIALS AND METHODS: 29 patients with painful hip and bone marrow edema
pattern of the proximal femur on non-contrast MR imaging were examined using
diffusion-weighted and dynamic gadolinium-enhanced sequences. Apparent diffusion
coefficients (ADCs) and perfusion parameters were calculated for different
regions of the proximal femur. Regional distribution and differences in ADC
values and perfusion parameters were evaluated. RESULTS: Seven patients presented
with TBME, 15 with AVN and seven with SIF of the proximal femur. Perfusion
imaging showed significant differences for maximum enhancement values (Emax),
slope (Eslope) and time to peak (TTP) between the three patient groups (p<0.05).
In contrast, no significant differences for ADC values were calculated when
comparing TBME, AVN, and SIF patients. CONCLUSION: Diffusion weighted imaging of
bone marrow of the proximal femur did not show significant differences between
patients with TBME, AVN or SIF. In contrast, MR perfusion imaging demonstrated
significant differences for the different patient groups and may as a
complementary imaging technique add information to the understanding of the
pathophysiology of diseases associated with bone marrow edema.
PMID- 25129826
TI - Involvement of threonine deaminase FgIlv1 in isoleucine biosynthesis and full
virulence in Fusarium graminearum.
AB - In this study we characterized FgIlv1, a homologue of the Saccharomyces
cerevisiae threonine dehydratase (TD) from the important Fusarium head blight
fungus Fusarium graminearum. TD catalyzes the first step in the biosynthesis
pathway of isoleucine (Ile) for conversion of threonine (Thr) to 2-ketobutyrate
(2-KB). The FgILV1 deletion mutant DeltaFgIlv1-3 was unable to grow on minimal
medium or fructose gelatin agar which lacked Ile. Exogenous supplementation of
Ile or 2-KB but not Thr rescued the mycelial growth defect of DeltaFgIlv1-3,
indicating the involvement of FgIlv1 in the conversion of Thr to 2-KB in Ile
biosynthesis. Additionally, exogenous supplementation of Methionine (Met) could
also rescue the mycelial growth defect of DeltaFgIlv1-3, indicating a crosstalk
between Ile biosynthesis and Met catabolism in F. graminearum. Deletion of FgILV1
also caused defects in conidial formation and germination. In addition,
DeltaFgIlv1-3 displayed decreased virulence on wheat heads and a low level of
deoxynivalenol (DON) production in wheat kernels. Taken together, results of this
study indicate that FgIlv1 is an essential component in Ile biosynthesis and is
required for various cellular processes including mycelial and conidial
morphogenesis, DON biosynthesis, and full virulence in F. graminearum. Our data
indicate the potential of targeting Ile biosynthesis for anti-FHB management.
PMID- 25129827
TI - In vitro properties of apheresis platelet during extended storage in plasma
treated with anandamide.
AB - BACKGROUND: In China apheresis platelets (PLTs) are stored in plasma for only 5
days, resulting in PLT inventory pressures. Anandamide (ANA) was reported to be a
potential agent to inhibit PLT apoptosis. The aim of this study was to evaluate
the characteristics of extended storage PLTs in plasma treated with ANA in vitro.
METHODS: Apheresis PLTs (n = 20) were prepared in plasma treated with ANA, and
stored at 22 degrees C for up to 11 days. On day 1, 3, 5, 7, 9 and 11, PLTs were
tested for PLT count, mean PLT volume (MPV), PLT distribution width (PDW), pH,
pCO(2), pO(2), hypotonic shock response (HSR), phosphatidylserine (PS) exposure
and soluble P-selectin content. RESULTS: PLTs stored in plasma with/without ANA
didn't show significant differences during the first 5 days of storage. From the
7(th) day on, PLTs stored in plasma with ANA displayed significantly lower PS
expression, soluble P-selectin content and higher HSR scores than those stored in
plasma without ANA (P <0.05), respectively. CONCLUSION: The extended storage of
PLTs in plasma treated with 0.5 umol/l ANA showed better characteristics of the
PLTs, compared with the control group, which was suggested to potentially
alleviate the PLT storage lesion.
PMID- 25129828
TI - Treatment of steroid resistant ulcerative colitis with severe autoimmune
haemolytic anaemia.
PMID- 25129829
TI - Use of aprotinin to reduce blood loss and transfusion in major orthopedic
surgery: a meta-analysis.
AB - BACKGROUD: Conflicting reports have been published regarding the effectiveness
and safety of aprotinin in reducing blood loss and transfusion in patients
undergoing orthopedic surgery. We performed a meta-analysis to evaluate the
effectiveness and safety of aprotinin in reducing blood loss and transfusion in
major orthopedic surgery. MATERIALS AND METHODS: MEDLINE, PubMed, EMBASE and
Cochrane databases were searched for relevant studies. Only randomized controlled
trials were eligible for this study. The weighted mean difference in blood loss,
and number of transfusions per patient and the summary risk ratio of transfusion
requirements, and deep-vein thrombosis (DVT) were calculated in the aprotinin
treated group and the control group. RESULTS: Eighteen randomized controlled
trials involving 1276 patients were included. The use of aprotinin reduced total
blood loss by a mean of 498.88 ml (95% confidence interval [CI]; -735.03 to
262.72), intra-operative blood loss by a mean of 246.11 ml (95% CI; -352.11 to
140.11), post-operative blood loss by a mean of 169.11 ml (95% CI; -234.06 to
105.55), the number of blood transfusions per patient by 0.93 units (95% CI;
1.36 to -0.51). Aprotinin led to a signficant reduction in transfusion
requirements (RR 0.59; 95% CI; 0.51 to 0.69) and no increase in the risk of DVT
(RR 0.58; 95% CI; 0.38 to 1.08). CONCLUSION: The meta-analysis shows that
aprotinin could significantly reduce blood loss and blood transfusion
requirements in patients undergoing orthopedic surgery, and it did not appear to
increase the risk of DVT.
PMID- 25129830
TI - Response to Al-Khabori M. et al.'s "validation of a non-invasive pulse CO
oximetry based hemoglobin estimation in normal blood donors," Transfusion and
Apheresis Science 2013 Nov 4. Accurate enough for blood donors? Not so fast.
PMID- 25129832
TI - Relationship between protozoan and metazoan communities and operation and
performance parameters in a textile sewage activated sludge system.
AB - The present study aims at investigating the possibility of assessing performance
and depuration conditions of an activated sludge wastewater treatment plant
through an exploration of the microfauna. The plant, receiving textile industrial
(70%) and domestic (30%) sewage, consists of a two-step biological depurating
plant, with activated sludge followed by a percolating system. A total of 35
samples were analyzed during five months, and 30 taxa of protozoa and small
metazoa were found. Epistylis rotans, Vorticella microstoma, Aspidisca cicada and
Arcella sp. were the most frequent protozoa identified. Several significant
correlations between biological, physical-chemical and operational parameters
were determined, but no significant correlations could be established between
biological parameters and removal efficiencies. The Sludge Biotic Index (SBI)
reflected the overall state of the community but only presented statistically
significant correlations with the influent total suspended solids (TSS), total
suspended solids in mixed-liquor (MLTSS) and dissolved oxygen (DO). The
determination of key groups and taxa along with general community parameters
showed to have potential value as indicators of the depuration conditions.
Despite the impossibility of correlating biological parameters and the removal
efficiencies, the present study attests the value of the microfauna to assess the
operation of the activated sludge systems even in the case of non-conventional
plants and/or plants receiving industrial sewage.
PMID- 25129833
TI - Multivariate morphometric analyses of the predatory ciliate genus Semispathidium
(Ciliophora: Litostomatea), with description of S. longiarmatum nov. spec.
AB - We studied morphometrical variation, species boundaries, and importance of
morphometric features for a reliable separation of five African Semispathidium
taxa. Altogether, 20 features traditionally used in alpha-taxonomy of the
predatory genus Semispathidium were measured or scored on 85 protargol
impregnated interphase specimens, and were analyzed using hierarchical clustering
as well as principal component and canonical discriminant analyses. This
multivariate approach confirmed that a population found in Botswanan floodplain
soil represents a distinct taxon. The new species is described here as S.
longiarmatum, using live observation, protargol impregnation, and scanning
electron microscopy. Semispathidium longiarmatum strongly resembles S. armatum
and S. breviarmatum but it is clearly distinguished from these species by the
extrusome pattern. The reliability of S. longiarmatum is also strengthened,
according to the canonical discriminant analysis, by several quantitative
features, viz., the number of ciliary rows, the length:width ratio of the
macronucleus, and the number of dikinetids in brush row 1. Moreover, the present
study documents the distinctness of all African Semispathidium species which can
be separated by a combination of both qualitative and quantitative (morphometric)
features. Consequently, Semispathidium species do not form a continuous complex
but fairly discrete clusters in the phenotypic space.
PMID- 25129831
TI - Childhood infections and trauma as risk factors for stroke.
AB - Stroke is as common as brain tumor in children. The etiology of childhood
arterial ischemic stroke (AIS) appears to be multifactorial, resulting from the
interaction between genetic predisposition and environmental triggers. The risk
factors for AIS in children are markedly different from the atherosclerotic risk
factors in adults. Trauma and infections have been identified as associations in
previous studies and are exposures of particular interest because of their
increased prevalence in the children. The aim of this review article is to
provide an overview of the research studies that have addressed the role of
infections and trauma in pediatric AIS.
PMID- 25129834
TI - Colonization dynamics of ciliate morphotypes modified by shifting sandy
sediments.
AB - Sandy stream-bed sediments colonized by a diverse ciliate community are subject
to various disturbance regimes. In microcosms, we investigated the effect of
sediment shifting on the colonization dynamics of 3 ciliate morphotypes differing
in morphology, behavior and feeding strategy. The dynamics of the ciliate
morphotypes inhabiting sediment pore water and overlying water were observed at 3
sediment shifting frequencies: (1) stable sediments, (2) periodically shifting
sediments such as migrating ripples, and (3) continuously shifting sediments as
occurring during scour events of the uppermost sediment. Sediment shifting
significantly affected the abundance and growth rate of the ciliate morphotypes.
The free-swimming filter feeder Dexiostoma campylum was vulnerable to washout by
sediment shifting since significantly higher numbers occurred in the overlying
water than in pore water. Abundance of D. campylum only increased in pore water
of stable sediments. On the contrary, the vagile grasper feeder Chilodonella
uncinata and the sessile filter feeder Vorticella convallaria had positive growth
rates and successfully colonized sediments that shifted periodically and
continuously. Thus, the spatio-temporal pattern of sediment dynamics acts as an
essential factor of impact on the structure, distribution and function of ciliate
communities in sand-bed streams.
PMID- 25129835
TI - Redescription of Atopospira galeata (Kahl, 1927) nov. comb. and A. violacea
(Kahl, 1926) nov. comb. with redefinition of Atopospira Jankowski, 1964 nov.
stat. and Brachonella Jankowski, 1964 (Ciliophora, Armophorida).
AB - The taxonomy of the Metopidae (Ciliophora, Armophorida) remains poorly understood
since most of its members have not been studied by modern morphologic and
molecular methods. Recent molecular investigations have indicated that the two
most species-rich genera, Metopus and Brachonella, are likely nonmonophyletic
with at least one well-supported 18S rDNA clade comprised of a species from each
of these genera (Brachonella galeata and Metopus violaceus). We investigated
these two species with silver impregnation and scanning electron microscopy. Both
taxa share important morphologic characteristics not described in other species
of Metopus or Brachonella. These synapomorphies include: (1) a diplostichomonad
paroral membrane, (2) a bipartite adoral zone with a short buccal part composed
of ordinary membranelles and a longer distal part composed of much smaller
membranelles bearing a single cilium or none and extending the same length as the
perzonal ciliary stripe. We transfer Brachonella galeata (Kahl, 1927) Jankowski,
1964 and Metopus violaceus Kahl, 1926 to genus Atopospira Jankowski, 1964 nov.
stat. Pending detailed morphologic and molecular characterization, Brachonella
campanula, B. cydonia and B. pyriforma, B. intercedens, and B. lemani remain in
Brachonella Jankowski 1964.
PMID- 25129836
TI - Morphology of Clapsiella magnifica gen. n., sp. n., a new hypotrichous ciliate
with a curious dorsal ciliary pattern.
AB - The present work describes the morphology and infraciliature of a new
hypotrichous ciliate, Clapsiella magnifica gen. n., sp. n., found in rewetted
soil from a temporal pond in Argentina. It was studied by means of live
observation and protargol impregnation. Its main diagnostic features are:
Flexible hypotrich measuring 250-320 MUm * 70-140 MUm in vivo; two macronuclear
nodules and 4-6 micronuclei. Single contractile vacuole. Cytoplasm transparent,
cortical granules absent. Somatic ciliature composed of a tricorona of cirri,
three buccal(?) cirri, 6-9 ventral rows, 3-5 right marginal(?) rows, one left
marginal row, and 12-17 transverse cirri. Dorsal pattern rather complicated, with
about 14 kineties and kinety fragments, with scattered kinetids among them; 17-28
caudal cirri arranged in three rows on dorsal kineties 1, 3, and 7. Remarkably,
dorsal kinetids have two or four basal bodies, bearing a stiff bristle arising
from left anterior basal body. Adoral zone composed of 70-92 membranelles,
occupying about 40% of body length in protargol preparations; paroral and endoral
curved, resembling a cyrtohymenid pattern. The peculiar dorsal ciliary
arrangement and the unique combination of other characters require the
establishment of a new genus for this new species, which is considered incertae
sedis in the Hypotricha but possibly related to the oxytrichids.
PMID- 25129837
TI - Ciliate communities of a large shallow lake: association with macrophyte beds.
AB - We investigated the influence of macrophyte composition on ciliate community
structure in a large, shallow, eutrophic Lake Vortsjarv. We hypothesized that
macrophyte composition must have strong influence on the dispersal of
ecologically different ciliate groups in a shallow lake and that more diverse
macrophyte stands cause also a greater diversity in the ciliate community. In
Vortsjarv macrophyte distribution is spatially strongly polarized both in east
west and north-south directions in relation to abiotic factors. Phragmites
australis and Myriophyllum spicatum were the most widespread species occurring in
most parts of the lake. Correlation of environmental, macrophyte and planktonic
ciliate variables confirmed the suggested spatial gradients. More diverse
macrophyte stands supported a high species richness and abundance of
epiplanktonic community but showed negative influence on the number and abundance
of euplanktonic ciliate taxa. Opposite trends were found relative to the
abundance of P. australis. Benthic ciliates showed a similar distribution pattern
to euplanktonic taxa being most abundant in sites were the Shannon-Weaver index
for macrophytes was low. Strong polarizing effect of the lake's vegetation on
planktonic ciliate diversity was reflected in correlations of the number of
ciliate taxa as well as the numbers of eu- and epiplanktonic taxa with geographic
co-ordinates.
PMID- 25129838
TI - Diurnal and twenty-four hour patterning of human diseases: cardiac, vascular, and
respiratory diseases, conditions, and syndromes.
AB - Various medical conditions, disorders, and syndromes exhibit predictable-in-time
diurnal and 24 h patterning in the signs, symptoms, and grave nonfatal and fatal
events, e.g., respiratory ones of viral and allergic rhinorrhea, reversible
(asthma) and non-reversible (bronchitis and emphysema) chronic obstructive
pulmonary disease, cystic fibrosis, high altitude pulmonary edema, and
decompression sickness; cardiac ones of atrial premature beats and tachycardia,
paroxysmal atrial fibrillation, 3rd degree atrial-ventricular block, paroxysmal
supraventricular tachycardia, ventricular premature beats, ventricular
tachyarrhythmia, symptomatic and non-symptomatic angina pectoris, Prinzmetal
vasospastic variant angina, acute (non-fatal and fatal) incidents of myocardial
infarction, sudden cardiac arrest, in-bed sudden death syndrome of type-1
diabetes, acute cardiogenic pulmonary edema, and heart failure; vascular and
circulatory system ones of hypertension, acute orthostatic postprandial,
micturition, and defecation hypotension/syncope, intermittent claudication,
venous insufficiency, standing occupation leg edema, arterial and venous branch
occlusion of the eye, menopausal hot flash, sickle cell syndrome, abdominal,
aortic, and thoracic dissections, pulmonary thromboembolism, and deep venous
thrombosis, and cerebrovascular transient ischemic attack and hemorrhagic and
ischemic stroke. Knowledge of these temporal patterns not only helps guide
patient care but research of their underlying endogenous mechanisms, i.e.,
circadian and others, and external triggers plus informs the development and
application of effective chronopreventive and chronotherapeutic strategies.
PMID- 25129839
TI - Diurnal and twenty-four hour patterning of human diseases: acute and chronic
common and uncommon medical conditions.
AB - The symptom intensity and mortality of human diseases, conditions, and syndromes
exhibit diurnal or 24 h patterning, e.g., skin: atopic dermatitis, urticaria,
psoriasis, and palmar hyperhidrosis; gastrointestinal: esophageal reflux, peptic
ulcer (including perforation and hemorrhage), cyclic vomiting syndrome, biliary
colic, hepatic variceal hemorrhage, and proctalgia fugax; infection:
susceptibility, fever, and mortality; neural: frontal, parietal, temporal, and
occipital lobe seizures, Parkinson's and Alzheimer's disease, hereditary
progressive dystonia, and pain (cancer, post-surgical, diabetic neuropathic and
foot ulcer, tooth caries, burning mouth and temporomandibular syndromes,
fibromyalgia, sciatica, intervertebral vacuum phenomenon, multiple sclerosis
muscle spasm, and migraine, tension, cluster, hypnic, and paroxysmal hemicranial
headache); renal: colic and nocturnal enuresis and polyuria; ocular: bulbar
conjunctival redness, keratoconjunctivitis sicca, intraocular pressure and
anterior ischemic optic neuropathy, and recurrent corneal erosion syndrome;
psychiatric/behavioral: major and seasonal affective depressive disorders,
bipolar disorder, parasuicide and suicide, dementia-associated agitation, and
addictive alcohol, tobacco, and heroin cravings and withdrawal phenomena; plus
autoimmune and musculoskeletal: rheumatoid arthritis, osteoarthritis, axial
spondylarthritis, gout, Sjogren's syndrome, and systemic lupus erythematosus.
Knowledge of these and other 24 h patterns of human pathophysiology informs
research of their underlying circadian and other endogenous mechanisms, external
temporal triggers, and more effective patient care entailing clinical
chronopreventive and chronotherapeutic strategies.
PMID- 25129840
TI - [Crystalluria in ethylene glycol intoxication].
AB - When seen, some habits of calcium oxalate monohydrate crystals (whewellite) are
so typical of ethylene glycol intoxication that they may be helpful for its
diagnosis when circumstances are not clearly established.
PMID- 25129841
TI - IT Infrastructure to support the secondary use of routinely acquired clinical
imaging data for research.
AB - We propose an infrastructure for the automated anonymization, extraction and
processing of image data stored in clinical data repositories to make routinely
acquired imaging data available for research purposes. The automated system,
which was tested in the context of analyzing routinely acquired MR brain imaging
data, consists of four modules: subject selection using PACS query, anonymization
of privacy sensitive information and removal of facial features, quality
assurance on DICOM header and image information, and quantitative imaging
biomarker extraction. In total, 1,616 examinations were selected based on the
following MRI scanning protocols: dementia protocol (246), multiple sclerosis
protocol (446) and open question protocol (924). We evaluated the effectiveness
of the infrastructure in accessing and successfully extracting biomarkers from
routinely acquired clinical imaging data. To examine the validity, we compared
brain volumes between patient groups with positive and negative diagnosis,
according to the patient reports. Overall, success rates of image data retrieval
and automatic processing were 82.5 %, 82.3 % and 66.2 % for the three protocol
groups respectively, indicating that a large percentage of routinely acquired
clinical imaging data can be used for brain volumetry research, despite image
heterogeneity. In line with the literature, brain volumes were found to be
significantly smaller (p-value <0.001) in patients with a positive diagnosis of
dementia (915 ml) compared to patients with a negative diagnosis (939 ml). This
study demonstrates that quantitative image biomarkers such as intracranial and
brain volume can be extracted from routinely acquired clinical imaging data. This
enables secondary use of clinical images for research into quantitative
biomarkers at a hitherto unprecedented scale.
PMID- 25129842
TI - Shwachman-Diamond syndrome with autoimmune-like liver disease and enteropathy
mimicking celiac disease.
AB - Liver abnormalities that normalize during infancy as well an enteropathy are
reported in Shwachman-Diamond syndrome (SDS). The pathogenesis of both conditions
is unknown. We report two SDS cases with autoimmune-like (antismooth muscle
and/or antinuclear antibody positivity) liver disease and antigliadin antibody
positive inflammatory enteropathy. Hypertransaminasemia did not resolve after
immunosuppressive therapy and/or a gluten-free diet. These transient autoimmune
phenomena and gut-liver axis perturbations may have played a role in transient
SDS hepatopathy and enteropathy. Our report may stimulate other studies to define
the relationship between the SDS genetic defect and intestinal permeability as
the pathogenic mechanism underlying SDS related liver and intestinal
inflammation.
PMID- 25129843
TI - Ertapenem induced hyperbilirubinemia.
PMID- 25129845
TI - Is guava phenolic metabolism influenced by elevated atmospheric CO2?
AB - Seedlings of Psidium guajava cv. Pedro Sato were distributed into four open-top
chambers: two with ambient CO(2) (~390 ppm) and two with elevated CO(2) (~780
ppm). Monthly, five individuals of each chamber were collected, separated into
root, stem and leaves and immediately frozen in liquid nitrogen. Chemical
parameters were analyzed to investigate how guava invests the surplus carbon. For
all classes of phenolic compounds analyzed only tannins showed significant
increase in plants at elevated CO(2) after 90 days. There was no significant
difference in dry biomass, but the leaves showed high accumulation of starch
under elevated CO(2). Results suggest that elevated CO(2) seems to be favorable
to seedlings of P. guajava, due to accumulation of starch and tannins, the latter
being an important anti-herbivore substance.
PMID- 25129846
TI - Resolution of airflow obstruction on polysomnography after laryngotracheal
reconstruction with anterior tracheal wall suspension in a patient with DiGeorge
Syndrome.
AB - DiGeorge Syndrome (DGS) may be associated with airway abnormalities including
laryngomalacia and suprastomal collapse of the trachea (SCT), which may lead to
sleep disordered breathing (SDB). We present a 4-year-old boy with DGS, SCT, and
SDB by polysomnography (PSG) while the tracheostomy tube was capped. The patient
underwent anterior tracheal wall suspension (ATWS) with concurrent tracheostomy
decannulation. Following the repair, the patient experienced improved airway
patency visually and by PSG with resolution of obstructive sleep apnea and
hypoventilation. ATWS is an effective method to repair SCT in selected patients
and may lead to early decannulation and improvement of SDB.
PMID- 25129844
TI - Adaptations to local environments in modern human populations.
AB - After leaving sub-Saharan Africa around 50000-100000 years ago, anatomically
modern humans have quickly occupied extremely diverse environments. Human
populations were exposed to further environmental changes resulting from cultural
innovations, such as the spread of farming, which gave rise to new selective
pressures related to pathogen exposures and dietary shifts. In addition to
changing the frequency of individual adaptive alleles, natural selection may also
shape the overall genetic architecture of adaptive traits. Here, we review recent
advances in understanding the genetic architecture of adaptive human phenotypes
based on insights from the studies of lactase persistence, skin pigmentation and
high-altitude adaptation. These adaptations evolved in parallel in multiple human
populations, providing a chance to investigate independent realizations of the
evolutionary process. We suggest that the outcome of adaptive evolution is often
highly variable even under similar selective pressures. Finally, we highlight a
growing need for detecting adaptations that did not follow the classical sweep
model and for incorporating new sources of genetic evidence such as information
from ancient DNA.
PMID- 25129848
TI - A new method of real-time skin dose visualization. Clinical evaluation of
fluoroscopically guided interventions.
AB - INTRODUCTION: We have conducted a prospective study to clinically evaluate a new
radiation dose observing tool that displays patient's peak skin dose (PSD) map in
real time. METHODS: The skin dose map (SDM) prototype quantifies the air kerma
based on exposure parameters from the X-ray system. The accuracy of this
prototype was evaluated with radiochromic films, which were used as a mean for
PSD measurement. RESULTS: The SDM is a reliable tool that provides an accurate
PSD estimation and location. CONCLUSION: SDM also has many advantages over the
radiochromic films, such as real-time dose evaluation and easy access to critical
operational parameters for physicians and technicians.
PMID- 25129847
TI - Acute airway obstruction by Ascaris lumbricoides in a 14-month-old boy.
AB - We describe the case of a 14-month-old child with airway obstruction caused by a
mature Ascaris lumbricoides worm. The child had been admitted to the paediatric
intensive care unit due to overwhelming sepsis, and during the course of his
illness developed acute airway obstruction that resolved once the worm was
removed from the airway. The Ascaris life-cycle is detailed, and a literature
review of patients with airway obstruction due to Ascaris worms is presented.
PMID- 25129849
TI - Severe depressive symptoms are associated with elevated endothelin-1 in younger
patients with acute coronary syndrome.
AB - OBJECTIVE: To explore the relationship of depressive symptom severity to
circulating endothelin (ET)-1 in younger patients with acute coronary syndrome
(ACS). Younger patients report greater depressive symptom severity, which
predicts poorer post-ACS prognosis. The pathways linking depression to post-ACS
prognosis require further elucidation. ET-1 is a potent endogenous
vasoconstrictor which has been previously linked to adverse post-ACS outcomes.
METHODS: The sample (n=153) included males <= 50 years of age and females <= 55
years of age who participated in a larger study. Blood samples for ET-1
assessment were collected within 2-3h of ACS admission. Depressive symptoms were
assessed with the Beck Depression Inventory (BDI) II within 2-5 days of
admission. ET-1 was treated as a transformed continuous variable (ET-1T). BDI-II
scores were classified into four categories using conventional thresholds
demarcating mild, moderate, and severe levels of depressive symptoms. The
relationship of classified BDI-II score to ET-1T was examined in simple and
multivariable linear regression models. RESULTS: Classified BDI-II score was
related to ET-1T in both unadjusted (chi(2)=9.469, p=0.024) and multivariable
(chi(2)=8.430, p=0.038) models, with ET-1T being significantly higher in patients
with severe depressive symptoms than in those with mild and moderate depressive
symptoms. CONCLUSIONS: In this sample of younger post-ACS patients, severe
depressive symptoms were associated with elevated ET-1. We acknowledge that the
observed association could be eliminated by the inclusion of some unmeasured
variable(s). Longitudinal research should examine whether ET-1 mediates the
relationship of depressive symptoms to long-term post-ACS outcomes.
PMID- 25129850
TI - Optimism measured pre-operatively is associated with reduced pain intensity and
physical symptom reporting after coronary artery bypass graft surgery.
AB - OBJECTIVE: Optimism is thought to be associated with long-term favourable
outcomes for patients undergoing coronary artery bypass graft (CABG) surgery. Our
objective was to examine the association between optimism and post-operative pain
and physical symptoms in CABG patients. METHODS: We assessed optimism pre
operatively in 197 adults undergoing CABG surgery, and then followed them up 6-8
weeks after the procedure to measure affective pain, pain intensity, and physical
symptom reporting directly pertaining to CABG surgery. RESULTS: Greater optimism
measured pre-operatively was significantly associated with lower pain intensity
(beta=-0.150, CI=-0.196 to -0.004, p=.042) and fewer physical symptoms following
surgery (beta=-0.287, CI=-0.537 to -0.036, p=.025), but not with affective pain,
after controlling for demographic, clinical and behavioural covariates, including
negative affectivity. CONCLUSIONS: Optimism is a modest, yet significant,
predictor of pain intensity and physical symptom reporting after CABG surgery.
Having positive expectations may promote better recovery.
PMID- 25129852
TI - Efficacy and safety of fronto-temporal transcranial random noise stimulation
(tRNS) in drug-free patients with schizophrenia: a case study.
PMID- 25129851
TI - Pithomyces species (Montagnulaceae) from clinical specimens: identification and
antifungal susceptibility profiles.
AB - The fungal genus Pithomyces comprises numerous dematiaceous saprobic species
commonly found on dead leaves and stems of a great variety of plants.
Occasionally, they have been recovered from clinical specimens. We
morphologically and molecularly (rDNA sequences) investigated a set of 42
isolates tentatively identified as Pithomyces recovered from clinical specimens
in the United States. The predominant species were P. chartarum and P. sacchari
(33.3% each), followed by Pithomyces sp. I (28.6%) and P. maydicus (4.8%). Most
of the isolates were obtained from samples of superficial tissue (50%), the
respiratory tract (21.4%), and the nasal region (19%). In general, these fungi
were highly susceptible in vitro to the eight antifungal agents tested.
PMID- 25129853
TI - Mere extension of the field of resection cannot be the answer to surgery for
metastatic spread: we need individualized approaches based on modern imaging
techniques.
PMID- 25129855
TI - Medical and molecular perspectives into a forgotten epidemic: encephalitis
lethargica, viruses, and high-throughput sequencing.
AB - The emergence of encephalitis lethargica (EL), an acute-onset polioencephalitis
of unknown etiology as an epidemic in the years 1917-1925 is still unexplainable
today. Questioned by the first descriptor of EL himself, Constantin von Economo,
there has been much debate shrouding a possible role of the "Spanish" H1N1
influenza A pandemic virus in the development of EL. Previous molecular studies
employing conventional PCR for the detection of influenza A virus RNA in archived
human brain samples from patients who died of acute EL were negative. However,
the clinical and laboratory characteristics of EL and its epidemiology are
consistent with an infectious disease, and recently a possible enterovirus cause
was investigated. With the rapid development of high-throughput sequencing, new
information about a possible viral etiology can be obtained if sufficient
specimens for analysis were still available today. Here, we discuss the
implications of these technologies for the investigation of a possible infectious
cause of EL from archived material, as well as a prospectus for future work for
acquiring viral nucleic acids from these sources.
PMID- 25129856
TI - A psoas abscess caused by Propionibacterium propionicum.
AB - Pelvic actinomycosis-like disease due to Propionibacterium propionicum has been
very rare and only a few cases have been reported in the literature. We herein
report a probable first case of a psoas abscess caused by P. propionicum. Since
P. propionicum is indistinguishable from Actinomyces israelii by morphological
features or routine biochemical tests, 16S rRNA gene sequencing was useful to
discriminate these two species in this case.
PMID- 25129854
TI - Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant
prostate cancer.
AB - BACKGROUND: Extracellular microRNAs (miRNAs) embedded in circulating exosomes may
serves as prognostic biomarkers in cancer. OBJECTIVE: To identify and evaluate
plasma exosomal miRNAs for prognosis in castration-resistant prostate cancer
(CRPC). DESIGN, SETTING, AND PARTICIPANTS: RNA sequencing was performed to
identify candidate exosomal miRNAs associated with overall survival in a
screening cohort of 23 CRPC patients. Candidate miRNAs were further evaluated for
prognosis using quantitative real-time polymerase chain reaction in a follow-up
cohort of 100 CRPC patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox
regression and Kaplan-Meier survival analyses were used to evaluate survival
association using candidate miRNAs along with clinical prognostic factors.
RESULTS AND LIMITATIONS: RNA sequencing in screening cohort generated
approximately 6.80 million mappable reads per patient. Of those with normalized
read counts >= 5, 43% were mapped to miRNAs for a total of 375 known and 57 novel
miRNAs. Cox regression analysis identified an association of miR-1290, -1246, and
-375 with overall survival (false discover rate < 0.05). Of those, higher levels
of miR-1290 and -375 were significantly associated with poor overall survival (p
< 0.004) in the follow-up cohort. Incorporation of miR-1290/-375 into putative
clinical prognostic factors-based models in CRPC stage significantly improved
predictive performance with a time-dependent area under the curve increase from
0.66 to 0.73 (p = 6.57 * 10(-6)). CONCLUSIONS: Plasma exosomal miR-1290 and miR
375 are promising prognostic biomarkers for CRPC patients. Prospective validation
is needed for further evaluation of these candidate miRNAs. PATIENT SUMMARY: In
this study, we evaluated whether small RNAs circulating in blood could be used to
predict clinical outcomes in late-stage prostate cancer patients. We identified
two blood-based small RNAs whose levels showed significant association with
survival. Our results warrant further investigation because the noninvasive blood
based test has great potential in the management of late-stage prostate cancer.
PMID- 25129857
TI - Urethral polyp-like lesions on prostatic urethra caused by Chlamydia trachomatis
infection: a case report.
AB - Urethral polyp is one of differential diagnoses for the male patients complain of
gross-hematuria and/or hematospermia. However, there have been limited numbers of
case reports including infectious etiology. Here we reported clinical course and
pathological findings of one rare case who was diagnosed and treated as urethral
polyp-like lesions on the prostatic urethra caused by Chlamydia trachomatis
infection. A 25 year-old man who had a past history of frequent sexual
intercourse with unspecified female sexual partner visited the clinic. His chief
complaint was gross-hematuria and hematospermia. Endoscopic findings showed that
non-specific hemorrhagic polyp-like lesions. To determine the pathological
findings including malignant diseases and diagnosis, transurethral resection was
performed. Because the pathological findings were similar to those of chlamydial
proctitis, additional examination was done. As the results, nucleic acid
amplification test of C. trachomatis in urine specimen was positive and
immunohistochemical staining of specific chlamydia antigen in resected specimen
was also positive. Treatment by orally minocyline 100 mg twice daily for 4 weeks
was introduced. After the treatment, symptom was disappeared and nucleic acid
amplification test of C. trachomatis in urine specimen turned to be negative. No
recurrence was reported 2 years posttreatment.
PMID- 25129858
TI - Normalization of nano-sized TiO2-induced clastogenicity, genotoxicity and
mutagenicity by chlorophyllin administration in mice brain, liver, and bone
marrow cells.
AB - The intensive uses of titanium dioxide (TiO2) nanoparticles in sunscreens,
toothpaste, sweats, medications, etc. making humans exposed to it daily by not
little amounts and also increased its risks including genotoxicity. Thus, the
present study was designed as one way to reduce nano-titanium-induced
clastogenicity, genotoxicity, and mutagenicity in mice by co-administration of
the free radical scavenger chlorophyllin (CHL). In addition, markers of oxidative
stress were detected to shed more light on mechanism(s) underlying nano-sized
TiO2 genotoxicity. Male mice were exposed to multiple injection into the
abdominal cavity for five consecutive days with either CHL (40 mg/kg bw/day), or
each of three dose levels of nano-sized TiO2 (500, 1000, or 2000 mg/kg bw/day)
alone, or both simultaneously and sacrificed by cervical dislocation 24 h after
the last treatment. After CHL co-administration, the observed dose-dependent
genotoxicity of TiO2 nanoparticles indicated by the significant elevations in
frequencies of both micronuclei and DNA damage induction was significantly
decreased and returned to the negative control level. The observed induced
mutations in p53 exons 5, 7, & 8 and 5 & 8 in the liver and brain, respectively,
were declined in most cases. Moreover, CHL significantly decreased hepatic
malondialdehyde level and significantly increased glutathione level and
superoxide dismutase, catalase, and glutathione peroxidase activities that were
significantly disrupted in animal groups treated with nano-TiO2 alone. In
conclusion, the evidenced in vivo genotoxicity of nano-TiO2 in the present study
was normalized after CHL co-administration which supports the previously
suggested oxidative stress as the possible mechanism for titanium toxicity.
PMID- 25129859
TI - Remarkable diversity of tick or mammalian-associated Borreliae in the
metropolitan San Francisco Bay Area, California.
AB - The diversity of Lyme disease (LD) and relapsing fever (RF)-group spirochetes in
the metropolitan San Francisco Bay area in northern California is poorly
understood. We tested Ixodes pacificus, I. spinipalpis, and small mammals for
presence of borreliae in Alameda County in the eastern portion of San Francisco
Bay between 2009 and 2012. Analyses of 218 Borrelia burgdorferi sensu lato (Bb
sl) culture or DNA isolates recovered from host-seeking I. pacificus ticks
revealed that the human pathogen Bb sensu stricto (hereinafter, B. burgdorferi)
had the broadest habitat distribution followed by B. bissettii. Three other North
American Bb sl spirochetes, B. americana, B. californiensis and B. genomospecies
2, also were detected at lower prevalence. OspC genotyping of the resultant 167
B. burgdorferi isolates revealed six ospC alleles (A, D, E3, F, H and K) in I.
pacificus. A novel spirochete belonging to the Eurasian Bb sl complex, designated
CA690, was found in a questing I. spinipalpis nymph. Borrelia miyamotoi, a
relapsing-fever (RF) group spirochete recently implicated as a human pathogen,
was detected in 24 I. pacificus. Three rodent species were infected with Bb sl:
the fox squirrel (Sciurus niger) with B. burgdorferi, and the dusky-footed wood
rat (Neotoma fuscipes) and roof rat (Rattus rattus) with B. bissettii. Another
spirochete that clustered phylogenetically with the Spanish R57 Borrelia sp. in a
clade distinct from both the LD and RF groups infected some of the roof rats.
Together, eight borrelial genospecies were detected in ticks or small mammals
from a single Californian county, two of which were related phylogenetically to
European spirochetes.
PMID- 25129860
TI - Distinct Anaplasma phagocytophilum genotypes associated with Ixodes trianguliceps
ticks and rodents in Central Europe.
AB - Rodents are important reservoir hosts of tick-borne pathogens. Anaplasma
phagocytophilum is the causative agent of granulocytic anaplasmosis of both
medical and veterinary importance. In Europe, this pathogen is primarily
transmitted by the Ixodes ricinus tick among a wide range of vertebrate hosts.
However, to what degree A. phagocytophilum exhibits host specificity and vector
association is poorly understood. To assess the extent of vector association of
this pathogen and to clarify its ecology in Central Europe we have analyzed and
compared the genetic variability of A. phagocytophilum strains from questing and
feeding I. ricinus and Ixodes trianguliceps ticks, as well as from rodent' tissue
samples. Tick collection and rodent trapping were performed during a 2-year study
(2011-2012) in ecologically contrasting setting at four sites in Eastern
Slovakia. Genetic variability of this pathogen was studied from the collected
samples by DNA amplification and sequencing of four loci followed by Bayesian
phylogenetic analyses. A. phagocytophilum was detected in questing I. ricinus
ticks (0.7%) from all studied sites and in host feeding I. trianguliceps ticks
(15.2%), as well as in rodent biopsies (ear - 1.6%, spleen - 2.2%), whereas A.
phagocytophilum was not detected in rodents from those sites where I.
trianguliceps ticks were absent. Moreover, Bayesian phylogenetic analyses have
shown the presence of two distinct clades, and tree topologies were concordant
for all four investigated loci. Importantly, the first clade contained A.
phagocytophilum genotypes from questing I. ricinus and feeding I. ricinus from a
broad array of hosts (i.e.,: humans, ungulates, birds and dogs). The second clade
comprised solely genotypes found in rodents and feeding I. trianguliceps. In this
study we have confirmed that A. phagocytophilum strains display specific host and
vector associations also in Central Europe similarly to A. phagocytophilum'
molecular ecology in United Kingdom. This study suggests that A. phagocytophilum
genotypes associated with rodents are probably transmitted solely by I.
trianguliceps ticks, thus implying that rodent-associated A. phagocytophilum
strains may not pose a risk for humans.
PMID- 25129861
TI - Dynamic loading of electrospun yarns guides mesenchymal stem cells towards a
tendon lineage.
AB - Alternative strategies are required when autograft tissue is not sufficient or
available to reconstruct damaged tendons. Electrospun fibre yarns could provide
such an alternative. This study investigates the seeding of human mesenchymal
stem cells (hMSC) on electrospun yarns and their response when subjected to
dynamic tensile loading. Cell seeded yarns sustained 3600 cycles per day for 21
days. Loaded yarns demonstrated a thickened cell layer around the scaffold's
exterior compared to statically cultured yarns, which would suggest an increased
rate of cell proliferation and/or matrix deposition, whilst maintaining a
predominant uniaxial cell orientation. Tensile properties of cell-seeded yarns
increased with time compared to acellular yarns. Loaded scaffolds demonstrated an
up-regulation in several key tendon genes, including collagen Type I. This study
demonstrates the support of hMSCs on electrospun yarns and their differentiation
towards a tendon lineage when mechanically stimulated.
PMID- 25129862
TI - Ligamentum teres injury is associated with the articular damage pattern in
patients with femoroacetabular impingement.
AB - PURPOSE: The objective of this study was to investigate the association between
ligamentum teres injury and the hip joint cartilage damage pattern in patients
with femoroacetabular impingement. METHODS: We compared articular cartilage
damage between ligamentum teres-intact and-ruptured hips. Data were collected for
77 consecutive patients with femoroacetabular impingement who underwent hip
arthroscopy. The locations of the chondral lesions were recorded on anatomic
articular maps using the geographic zone method. The patients were divided into 2
groups (ligamentum teres-intact and-injured groups), and the incidence and degree
of cartilage injury were compared between the 2 groups by use of the Mann-Whitney
U test. RESULTS: In patients with ligamentum teres injury, chondral damage
extended to the middle-inferior area of the acetabulum (7.6% [grade 1] in
ligamentum teres-intact group and 66.6% [grade 1, 12.1%; grade 2, 42.4%; grade 3,
12.1%] in ligamentum teres-injured group, P < .01) and the apex of the femoral
head (anterior apex: 7.1% [grade 1, 3.8%; grade 2, 3.3%] in intact group and
42.4% [grade 1, 30.3%; grade 2, 12.1%] in injured group, P < .01; middle apex:
7.6% [grade 1, 3.8%; grade 2, 3.8%] in intact group and 63.5% [grade 1, 42.4%;
grade 2, 18.1%; grade 3, 3.0%] in injured group, P = .04; posterior apex: 7.6%
[grade 1, 3.8%; grade 2, 3.8%] in intact group and 42.4% [grade 1, 30.3%; grade
2, 12.1%] in injured group, P < .01). CONCLUSIONS: This study showed the
association between ligamentum teres injury and articular cartilage damage in the
inferior middle part of the acetabulum and the apex of the femoral head in
patients treated for femoroacetabular impingement. LEVEL OF EVIDENCE: Level IV,
case-control study.
PMID- 25129863
TI - Effects of varying locations for biceps tendon tenotomy and superior labral
integrity on shoulder stability in a cadaveric concavity-compression model.
AB - PURPOSE: The purpose of this study was to examine the location of biceps tenotomy
and the integrity of the superior labrum as they relate to superior glenohumeral
joint stability in a cadaveric concavity-compression model. METHODS: Eight
cadaveric glenoid labrums were mounted individually onto a load cell with the
corresponding humerus fixed to the loading arm in the hanging-arm position. All
surrounding soft tissue was removed except the labrum and proximal stump of the
long head of the biceps (LHB) tendon, simulating a biceps tenotomy. A compressive
load of 22 N was applied across the glenohumeral joint. The humerus was then
translated superiorly until it subluxated over the glenoid labrum. The force
resisting superior translation was characterized for each of 50 cycles. Each
specimen was tested under the following conditions: (1) with a 4 cm biceps stump
after tenotomy, (2) with a 0 cm biceps stump, (3) after full detachment of the
superior labrum, and (4) after repair of the labrum. RESULTS: Biceps tenotomy
performed at the biceps-labral junction resulted in an average decrease in force
required to superiorly subluxate the humeral head by 8.6% (P = .01) when compared
with leaving 4 cm of biceps stump. Resection of the entire superior labrum
resulted in a future decrease to 15.2% (P < .001) from baseline. Repair of the
labrum resulted in restoration of stability with a mean of 101.1% (P = .82) and
was not statistically different from baseline. The kinematics of the glenohumeral
joint was affected by labral repair, with an earlier upslope on the force-to
displacement curve and alteration in the total energy required to cause
subluxation of the humeral head noted. CONCLUSIONS: In this study, location of
the biceps tenotomy and integrity of the superior labrum affected glenohumeral
stability during axial loading in the hanging-arm position. Repair of the labrum
restored stability for superior subluxation but also changed the kinematics of
the subluxation event. CLINICAL RELEVANCE: Preservation of superior labrum after
biceps tenotomy provides increased resistive force to superior translation in a
unidirectional biomechanical model.
PMID- 25129864
TI - Preliminary development of a clinical prediction rule for treatment of patients
with suspected SLAP tears.
AB - PURPOSE: To use the clinical prediction rule process to identify patient
variables, measured on initial clinical presentation, that would be predictive of
failure to achieve satisfactory improvement, while following a rehabilitation
program, in the modification of SLAP injury symptoms and dysfunction. METHODS: A
cohort of patients received the clinical diagnosis of a SLAP lesion based on
specific history and examination findings and/or magnetic resonance imaging. They
underwent a physical examination of the kinetic chain and shoulder, including
tests for labral injury. Patients followed a standardized physical therapy
program emphasizing restoration of demonstrated strength, flexibility, and
strength-balance deficits. At 6 weeks' follow-up, patients were re-evaluated and
divided into those recommended for surgery (RS) and those not recommended for
surgery (NRS). Bivariate logistic regression was performed to identify the best
combination of predictive factors. RESULTS: Fifty-eight patients (aged 39 +/- 11
years, 45 men) were included. Of these, 31 (53%) were categorized as NRS and 27
(47%) as RS. The presence of a painful arc of motion (odds ratio, 3.95; P = .024)
and the presence of increased forward scapular posture (odds ratio, 1.27; P =
.094) on the injured side were predictive of being in the RS group. This finding
indicates that the odds of being in the RS group increased 4 times when a
positive painful arc was present and increased 27% with every 1-cm increase in
involved anterior shoulder posture. CONCLUSIONS: A structured rehabilitation
program resulted in modification of symptoms and improved function at 6 weeks'
follow-up in over half of patients in the study group. On initial evaluation, the
presence of a painful arc of overhead motion, indicating loss of normal
glenohumeral kinematics, and the presence of forward shoulder posture, indicating
an altered scapular position, represent negative predictive factors for success
of rehabilitation. Future validation of the model in a larger population is
necessary. LEVEL OF EVIDENCE: Level II, prospective comparative study.
PMID- 25129865
TI - The role of arthroscopy in the management of glenohumeral osteoarthritis: a
Markov decision model.
AB - PURPOSE: The purposes of this study were (1) to construct a theoretical Markov
decision model to compare the total remaining quality-adjusted life-years
following either arthroscopic management (AM) or total shoulder arthroplasty
(TSA) for the treatment of glenohumeral osteoarthritis and (2) to determine the
possible effects of age on the preferred treatment strategy. METHODS: A Markov
decision model was constructed to compare AM and TSA in patients with
glenohumeral osteoarthritis. The rates of surgical complications, revision
surgery, and death were derived from the literature and analyzed. The principal
outcome measure was the mean total remaining quality-adjusted life-years after
each treatment strategy. Sensitivity analyses were performed for age at the
initial procedure, utilities, and transition probabilities. RESULTS: This
theoretical decision model showed that AM was the preferred strategy for patients
younger than 47 years, TSA was the preferred strategy for patients older than 66
years, and both treatment strategies were reasonable for patients aged between 47
and 66 years. The model was highly sensitive to age at the index surgery,
utilities of wellness states, survivorship, and the probability of failure after
either AM or TSA. CONCLUSIONS: According to this theoretical decision model, AM
was the preferred treatment strategy for patients younger than 47 years, primary
TSA was the preferred treatment strategy for patients older than 66 years, and
both treatment options were reasonable for patients aged between 47 and 66 years.
LEVEL OF EVIDENCE: Level II, economic and decision analysis.
PMID- 25129866
TI - Gait and lower extremity kinematic analysis as an outcome measure after
femoroacetabular impingement surgery.
AB - PURPOSE: Lower extremity and pelvis kinematics have been shown to be abnormal in
patients with femoroacetabular impingement (FAI). We conducted this systematic
review to evaluate the current status of gait and lower extremity kinematics as
an outcome measure in patients treated surgically for FAI. METHODS: We searched
the Embase, Medline, and PubMed databases for all reports of studies published
through February 22, 2014, evaluating kinematic assessment of patients undergoing
FAI surgery. A review of eligible studies was conducted, and the references were
searched. Methodologic quality was evaluated for all studies that met the
inclusion and exclusion criteria, and data were extracted regarding methods of
kinematic assessment and clinical and kinematic outcomes. RESULTS: We identified
633 reports, of which 5 met our eligibility criteria. These studies included a
total of 58 patients with symptomatic FAI (age range, 18 to 50 years). All
included studies were of moderate methodologic quality. Kinematic assessments
were completed preoperatively and postoperatively with variable methodology and
follow-up (range, 3 to 32 months). Most studies used high-speed motion-capture
camera systems with reflective tracking markers to evaluate in vivo kinematic
function. Of the 5 included studies, 3 documented kinematic improvements
postoperatively particularly regarding sagittal hip range of motion primarily
with flexion (weighted mean, 35.1 degrees +/- 5.4 degrees preoperatively and
37.8 degrees +/- 6.3 degrees postoperatively). CONCLUSIONS: Gait and lower
extremity kinematics can be used as an outcome measure after FAI surgery.
However, the lack of uniformity in the methodology used and underpowered case
series limit the ability to identify clear and predictable differences after
corrective surgery for FAI. Though statistically significant, functional outcome
improvements were often conflicting and not necessarily of clinical significance.
A uniform outcome measure and technique to reliably assess in vivo hip motion are
required for future comparative studies. LEVEL OF EVIDENCE: Level IV, systematic
review of Level IV studies.
PMID- 25129867
TI - Synthesis of heteroaryl/aryl kojic acid conjugates as stimulators of glucose
uptake by GLUT4 translocation.
AB - Insulin exerts its metabolic actions through the insulin receptor (IR) and plays
an essential role in treatment of diabetes. The inconvenience of daily injections
and the undesirable side-effects associated with insulin injections demand novel
drugs for the disease. To search for bioactive insulin mimetic, we synthesized a
chemical library of small molecules (2a-3f) based on the indolylkojic acid
scaffold (B). An In vitro screening assay was performed to stimulate glucose
transport in rat L6 skeletal muscle cells, post treatment of the compounds (2a
3f) for the time period incubation of 16 h. Compounds 2f, 2g, 2l, 3a, 3b, 3c and
3d have shown significant glucose uptake stimulation as compared to the controls
at micromolar concentrations. In mechanistic studies, we observed that these
compounds exert their biological action by enhancing GLUT4 translocation to cell
surface via PI3K-dependent signalling pathway in agreement to the insulin mode of
action. Hence, these promising conjugates should be useful for further drug
development in diabetes treatment.
PMID- 25129868
TI - Sequential synthesis of amino-1,4-naphthoquinone-appended triazoles and triazole
chromene hybrids and their antimycobacterial evaluation.
AB - A general method for the synthesis of a library of hitherto unreported amino-1,4
naphthoquinone-appended triazoles was accomplished via a sequential three
component reaction of substituted N-propargylaminonaphthoquinones with variously
substituted alkyl bromides/2-bromonaphthalene-1,4-dione and sodium azide in the
presence of Et3N/CuI in water. Aminonaphthoquinone-appended iminochromene
triazole hybrid heterocycles were also synthesized from the amino-1,4
naphthoquinone-appended-1,2,3-triazolylacetonitriles. All the triazole hybrids
were screened for their in vitro activity against Mycobacterium tuberculosis
H37Rv (MTB). Among the triazoles, 2-(((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)(4
(trifluoromethyl)phenyl)amino)naphthalene-1,4-dione (7d) emerged as the most
active one with IC50 = 1.87 MUM, being more potent than the anti-TB drugs,
cycloserine (6 times), pyrimethamine (20 times) and equipotent as the drug
ethambutol (IC50 < 1.56 MUM).
PMID- 25129869
TI - Capsaicin cough threshold test in diagnostics.
AB - BACKGROUND: Among patients with chronic unexplained cough, there is a recognized
subgroup with respiratory symptoms induced by environmental irritants like
chemicals and odours. The diagnosis of sensory hyperreactivity (SHR) has been
suggested for this group of patients and can be made using a tidal breathing
capsaicin inhalation test. The aim of the present study was to evaluate the
ability of a single-breath, dose-response capsaicin threshold test to
discriminate such patients from control subjects. METHODS: A total of 46 patients
with chronic cough and SHR who had previously shown a positive reaction in
accordance with limits set for a tidal breathing capsaicin test were tested once
with a single-breath, dose-response capsaicin cough threshold test, assessing
capsaicin concentrations to evoke 2 (C2), 5 (C5) or 10 (C10) coughs. Twenty-nine
subjectively healthy control subjects were also included and tested with the
threshold method. RESULTS: Patients had significantly lower C2, C5 and C10 in
comparison to controls. From the results among patients and controls, sensitivity
and specificity were calculated, and a receiver operating characteristic curve
was constructed, showing excellent ability for C5 and C10 to discriminate
patients from control subjects. CONCLUSIONS: For patients with SHR and chronic
cough, capsaicin cough sensitivity was once again confirmed to be increased, in
this case, using the single-breath dose-response method. Limits set for cough
reactions regarded as more sensitive than normal can be useful in diagnostics and
further research. C5 seems to be the best measure to use in research and
differential diagnostics.
PMID- 25129870
TI - Expression of adiponectin and adiponectin receptors 1 and 2 in the porcine
uterus, conceptus, and trophoblast during early pregnancy.
AB - Adiponectin, one of the several adipocytokines secreted mainly by the adipose
tissue, plays an important role in regulating energy homeostasis and controls
female fertility. Female reproductive functions are closely associated with
nutritional status, and adiponectin seems to be an important factor linking the
regulation of metabolic homeostasis with reproductive processes. The biological
activity of adiponectin is mediated by two distinct receptors, adiponectin
receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). The objective of this
study was to determine the presence of and changes in the gene and protein
expression pattern of adiponectin and its receptors in the porcine uterus during
early pregnancy and on Days 10 to 11 of the estrous cycle and in the conceptus
and trophoblast. The highest level of adiponectin transcript was observed on Days
15 to 16 of gestation, Days 10 to 11 of the cycle in the endometrium, and Days 15
to 16 of gestation in the myometrium. The highest expression of AdipoR1 and
AdipoR2 genes was detected on Days 10 to 11 of gestation in the endometrium, and
Days 12 to 13 in the myometrium. The highest content of adiponectin protein was
noted on Days 12 to 13 and 30 to 32 of gestation in the endometrium and Days 10
to 11 of the cycle in the myometrium. The expression of adiponectin protein was
higher on Days 27 to 28 and 30 to 32 in the conceptuses. AdipoR1 protein content
in the myometrium was highest on Days 12 to 13 and 30 to 32. In contrast, in the
endometrium, it was more constant. The highest content of AdipoR2 protein was
detected on Days 15 to 16 and 30 to 32 of gestation, Days 10 to 11 of the cycle
in the endometrium, and Days 10 to 11 of gestation in the myometrium. In the
conceptuses, the highest AdipoR1 protein content was observed on Days 15 to 16,
and the highest AdipoR2 protein expression was determined on Days 15 to 16 and 27
to 28. In the trophoblasts, AdipoR1 protein content was higher on Days 27 to 28
than on Days 30 to 32, whereas the expression of AdipoR2 was higher on Days 30 to
32. This study demonstrated the presence of adiponectin and its receptors in the
uteri, conceptuses, and trophoblasts of pregnant pigs and that the local
adiponectin system is dependent on the stage of pregnancy.
PMID- 25129871
TI - Hydroxyflutamide alters the characteristics of live boar spermatozoa.
AB - Our previous study revealed that in vitro incubation of boar ejaculates with
hydroxyflutamide (OH-Flu) causes changes in sperm plasma membrane integrity and
its stability and sperm mitochondrial oxidative capability. To broaden the
knowledge of cellular physiology of spermatozoa, we investigated direct effects
of OH-Flu administered for 2 and 24 hours at concentrations of 5, 50, and 100
MUg/mL, on sperm mitochondrial membrane potential and mitochondrial superoxide
anion production using JC-1 dye and MitoSOX Red fluorescent probe, respectively.
We further measured phosphatidylserine membrane translocation (PST) from the
inner to the outer layer of the sperm plasma membrane using an annexin-V binding
assay. To provide new information of direct effects of OH-Flu on cell signaling
pathway, we measured sperm intracellular calcium ion dynamics using Fluo-3.
Finally, we assessed sperm motility using a computer-assisted spermatozoa
analysis system. Motile sperm were highlighted using the "C-Ruch" computer
program for detailed analysis of the straight line velocity distribution. For
each functional test, boar spermatozoa were examined and analyzed by flow
cytometry and/or confocal microscopy. The results revealed a significant decrease
(P<0.05) in sperm mitochondrial membrane potential and a concomitant increase
(P<0.05) in mitochondrial superoxide anion production after a 2-hour incubation
with 50 MUg OH-Flu compared with the respective controls and other doses used
(P<0.05). The adverse effects of OH-Flu become strengthened over time (P<0.05).
Notably, 50 and 100 MUg OH-Flu appeared to be effective in decreasing sperm
motility. Hydroxyflutamide significantly decreased (P<0.05) the fast sperm
subpopulation percentage after 15 minutes and reduced the straight line velocity
distribution (P<0.05). An assessment of PST revealed an increase in the
percentage of PST-positive spermatozoa (P<0.05) only after exposure to OH-Flu for
24 hours. Moreover, OH-Flu at all concentrations induced a rapid increase in
sperm intracellular calcium ion concentration. Altogether, the altered in vitro
characteristics of live boar spermatozoa provide new insight into direct effects
of OH-Flu on sperm mitochondrial membrane potential, superoxide anion production,
translocation of membrane phosphatidylserine, free calcium ion dynamics, and
sperm motility.
PMID- 25129872
TI - DNA fragmentation and sperm head morphometry in cat epididymal spermatozoa.
AB - Sperm DNA fragmentation is an important parameter to assess sperm quality and can
be a putative fertility predictor. Because the sperm head consists almost
entirely of DNA, subtle differences in sperm head morphometry might be related to
DNA status. Several techniques are available to analyze sperm DNA fragmentation,
but they are labor-intensive and require expensive instrumentations. Recently, a
kit (Sperm-Halomax) based on the sperm chromatin dispersion test and developed
for spermatozoa of different species, but not for cat spermatozoa, became
commercially available. The first aim of the present study was to verify the
suitability of Sperm-Halomax assay, specifically developed for canine semen, for
the evaluation of DNA fragmentation of epididymal cat spermatozoa. For this
purpose, DNA fragmentation indexes (DFIs) obtained with Sperm-Halomax and
terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) were
compared. The second aim was to investigate whether a correlation between DNA
status, sperm head morphology, and morphometry assessed by computer-assisted
semen analysis exists in cat epididymal spermatozoa. No differences were observed
in DFIs obtained with Sperm-Halomax and TUNEL. This result indicates that Sperm
Halomax assay provides a reliable evaluation of DNA fragmentation of epididymal
feline spermatozoa. The DFI seems to be independent from all the measured
variables of sperm head morphology and morphometry. Thus, the evaluation of the
DNA status of spermatozoa could effectively contribute to the completion of the
standard analysis of fresh or frozen semen used in assisted reproductive
technologies.
PMID- 25129873
TI - Neuroimaging findings in primary insomnia.
AB - State-of-the-art neuroimaging techniques have accelerated progress in the study
and understanding of sleep in humans. Neuroimaging studies in primary insomnia
remain relatively few, considering the important prevalence of this disorder in
the general population. This review examines the contribution of functional and
structural neuroimaging to our current understanding of primary insomnia.
Functional studies during sleep provided support for the hyperarousal theory of
insomnia. Functional neuroimaging also revealed abnormalities in cognitive and
emotional processing in primary insomnia. Results from structural studies suggest
neuroanatomical alterations in primary insomnia, mostly in the hippocampus,
anterior cingulate cortex and orbitofrontal cortex. However, these results are
not well replicated across studies. A few magnetic resonance spectroscopy studies
revealed abnormalities in neurotransmitter concentrations and bioenergetics in
primary insomnia. The inconsistencies among neuroimaging findings on insomnia are
likely due to clinical heterogeneity, differences in imaging and overall
diversity of techniques and designs employed. Larger samples, replication, as
well as innovative methodologies are necessary for the progression of this
perplexing, yet promising area of research.
PMID- 25129874
TI - Emotional maltreatment and disordered eating in adolescents: testing the
mediating role of emotion regulation.
AB - The present study aimed to determine if emotion regulation mediates the
relationship between emotional maltreatment and disordered eating behavior in
adolescents. Participants were 222 secondary school pupils (aged 14-18 years)
from a state high school in the UK. Standardized questionnaire measures were used
to gather self-report data on emotional abuse and emotional neglect, functional
and dysfunctional emotion regulation strategies and disordered eating behavior.
Results showed that disordered eating was associated with emotional abuse,
dysfunctional emotion regulation and being female. Multiple mediation analysis
found an indirect relationship between emotional abuse and disordered eating
through dysfunctional emotion regulation. Interestingly, emotional neglect
predicted lower levels of functional emotion regulation. The findings support
previous research showing emotion regulation to mediate the relationship between
childhood abuse and disordered eating in adults and a differential effect of
abuse and neglect on emotion regulation. Longitudinal studies are required to
confirm the direction of relationships; however these data suggest that
dysfunctional emotion regulation is a significant variable in the development of
disordered eating and may be a useful target for intervention.
PMID- 25129875
TI - Cadmium concentrations and their implications in Mallard and Coot from fish pond
areas.
AB - During the studies in 2003, high concentrations of cadmium (Cd) were noted among
Mallards and Coots in Poland. Further research, five years later, showed the
histopathological alterations in birds from the same area which were probably
stimulated by Cd. This paper presents the analysis of Cd in ten different
materials collected from these species (n=180) in years 2006-2009 in two areas,
including southern - Zator and western Poland - Milicz. Similarly high
concentrations to those from 2003 were noted only in kidneys of Mallards from the
Zator area (up to 56.49 MUg g(-1) d.w.). Other comparable materials accumulated
significantly lower concentration of Cd. Generally, lower concentrations occurred
in birds from Milicz. Concentrations varied also between species and age groups.
They correlated between liver and kidneys, brain and muscle and brain and spleen.
Potential in vivo bioindicators (blood, feathers and excrements) did not seem to
be useful as biomarkers in both areas.
PMID- 25129876
TI - Comparison of accuracy of two different methods to determine ankle-brachial index
to predict peripheral arterial disease severity confirmed by angiography.
AB - Ankle-brachial index (ABI) is conventionally derived as the ratio of higher of
the 2 systolic ankle blood pressures to the higher brachial pressure (HABI
method). Alternatively, ABI may be derived using the lower of the 2 systolic
ankle pressures (LABI method). The objective of this study was to assess the
utility and difference between 2 techniques in predicting peripheral artery
disease (PAD). Participants who underwent both ABI measurement and arteriography
from July 2005 to June 2010 were reviewed. Angiographic disease burden was scored
semiquantitatively (0=<50%, 1=50% to 75%, and 2=>75% stenosis of any lower
extremity arterial segment), and PAD by angiography was defined as >50% stenosis
of any 1 lower extremity arterial segment. A combined PAD disease score was
calculated for each leg. A total of 130 patients were enrolled (260 limbs). The
ABI was <0.9 (abnormal) in 68% of patients by HABI method and in 84% by LABI.
LABI method had higher sensitivity and overall accuracy to detect PAD compared
with the HABI method. Regression analysis showed that an abnormal ABI detected by
LABI method is more likely to predict angiographic PAD and total PAD burden
compared with HABI. Moreover, abnormal ABI by LABI method had higher sensitivity
and accuracy to detect PAD in patients with diabetes and below knee PAD compared
with the HABI method. In conclusion, ABI determined by the LABI method has higher
sensitivity and is a better predictor of PAD compared with the conventional
(HABI) method.
PMID- 25129877
TI - Alcohol consumption and risk of death in male physicians with heart failure.
AB - The 5-year risk of death after onset of heart failure (HF) is about 50%. Although
previous studies have shown beneficial effects of light-to-moderate alcohol
consumption and risk of cardiovascular diseases and mortality, it is unclear
whether moderate alcohol consumption is associated with a lower risk of death in
subjects with HF. We investigated whether alcohol consumption and type of alcohol
preference are associated with the risk of total mortality in 449 US male
physicians with prevalent HF. Alcohol consumption was assessed through food
frequency questionnaire, and mortality was ascertained through annual follow-up
questionnaires and adjudicated by an Endpoint Committee. The mean age of subjects
was 75.7+/-8.2 years with an average follow-up of 7 years. We found evidence of a
J-shaped relation between alcohol consumption and mortality (hazard ratio [95%
confidence interval] 1.00 [reference], 0.85 [0.61 to 1.20], 0.60 [0.40 to 0.88],
and 0.71 [0.42 to 1.21] for alcohol intake of none, <1 drink/day, 1 to 2
drinks/day, and 3+ drinks/day, respectively [p for quadratic trend=0.058]). There
was no relation between beverage preference (beer, wine, or liquor) and
mortality. In conclusion, our data showed a J-shaped association between alcohol
intake and mortality in patients with HF.
PMID- 25129878
TI - Subclinical myocardial injury identified by cardiac infarction/injury score and
the risk of mortality in men and women free of cardiovascular disease.
AB - Previous studies have explored the ability of the Cardiac Infarction/Injury Score
(CIIS) to identify individuals who are high risk for cardiovascular disease (CVD)
mortality. However, its prognostic significance among those without CVD in the
United States general population has not been established. This analysis included
6,298 participants (mean age 59+/-13 years, 53% women, 51% nonwhites) from the
Third National Health and Nutrition Examination Survey, excluding participants
with a history of CVD or electrocardiographic evidence of old myocardial
infarction or ischemic ST depression at baseline. Subclinical myocardial injury
was defined as CIIS>=10. Mortality data were ascertained using the National Death
Index. Cox proportional hazards regression was used to compute hazard ratios
(HRs) and 95% confidence intervals (95% CIs) for the association between
subclinical myocardial injury and CVD and all-cause mortalities. Subclinical
myocardial injury was detected in 1,376 participants (22%). A total of 1,928
deaths occurred during a median follow-up of 14 years of which 765 (40%) were due
to CVD. In a multivariate model adjusted for demographics, traditional CVD risk
factors, and other medical co-morbidities, subclinical myocardial injury was
associated with an increased risk of CVD (HR 1.26, 95% CI 1.02 to 1.56) and all
cause (HR 1.42, 95% CI 1.23 to 1.63) mortalities. In conclusion, subclinical
myocardial injury in those without manifestations of CVD is associated with an
increased risk of CVD and all-cause mortalities. These findings highlight the
important role of CIIS to identify subclinical myocardial injury and its
association with mortality among men and women in the United States.
PMID- 25129879
TI - Determination of organophosphorus pesticides in stomach contents of postmortem
animals by QuEChERS and gas chromatography.
AB - The quick, easy, cheap, effective, rugged and safe (QuEChERS) method for sample
preparation was applied to determine seven organophosphorus pesticides (OPs) in
stomach contents of poisoned postmortem animals. The pesticides consisted of
diazinon, edifenphos, ethyl p-nitrophenyl phenylphosphonothioate, fenitrothion,
monocrotophos, parathion and phosphamindon, and tested samples included stomach
contents from postmortem animals of cattle, goat, dog, cat, birds, deer and
rabbit. The pesticides were spiked into the samples which were found to be
negative through previous pesticide poisoning analysis, and the pesticides were
extracted and cleaned up based on the QuEChERS process and then they were
analyzed using gas chromatography (GC)-flame photometric detector (FPD) or GC
nitrogen-phosphorus detector (NPD) with a DB-5 column. Limits of detection ranged
from 0.27 to 0.41 mg/kg for the seven pesticides. The mean recoveries ranged from
80 to 99% in GC-FPD and 83 to 90% in GC-NPD. The coefficients of variation were
<10% for all analytes and sample matrix combinations except for phosphamidon and
edifenphos in dog stomach contents. This study demonstrated that the method using
QuEChERS and GC-FPD and/or GC-NPD is very effective to analyze the OPs in the
stomach contents of postmortem animals.
PMID- 25129880
TI - Cardiac autonomic responses induced by mental tasks and the influence of musical
auditory stimulation.
AB - We investigated the acute effects of musical auditory stimulation on cardiac
autonomic responses to a mental task in 28 healthy men (18-22 years old). In the
control protocol (no music), the volunteers remained at seated rest for 10 min
and the test was applied for five minutes. After the end of test the subjects
remained seated for five more minutes. In the music protocol, the volunteers
remained at seated rest for 10 min, then were exposed to music for 10 min; the
test was then applied over five minutes, and the subjects remained seated for
five more minutes after the test. In the control and music protocols the time
domain and frequency domain indices of heart rate variability remained unchanged
before, during and after the test. We found that musical auditory stimulation
with baroque music did not influence cardiac autonomic responses to the mental
task.
PMID- 25129881
TI - Additional effects of homeopathy on chronic periodontitis: a 1-year follow-up
randomized clinical trial.
AB - BACKGROUND AND OBJECTIVE: The aim of this study was test the hypothesis that
homeopathy (H) enhances the effects of scaling and root planing (SRP) in patients
with chronic periodontitis (CP). MATERIALS AND METHODS: 50 patients with CP were
randomly allocated to one of two treatment groups: SRP (C-G) or SRP + H (H-G).
Assessments were made at baseline and after 3 and 12 months of treatments. The
local and systemic responses to the treatments were evaluated by clinical and
serologic parameters, respectively. RESULTS: Both groups displayed significant
improvements, however, using clinical attachment gain and reductions in HDL, LDL
and Total Cholesterol, Triglycerides, Glucose and Uric acid, from baseline to 1
year, as criteria for treatment success, H-G performed significantly better than
C-G. CONCLUSION: The findings of this 1-year follow-up randomized clinical trial
suggest that homeopathic medicines, as an adjunctive to SRP, can provide
significant local and systemic improvements for CP patients.
PMID- 25129882
TI - The effects of family-friend visits on anxiety, physiological indices and well
being of MI patients admitted to a coronary care unit.
AB - OBJECTIVE: To investigate the effect of family-friend visits on anxiety,
physiological indices and well-being of patients with acute myocardial
infarction. METHODS: A checklist was used to gather socio-demographic data and
physiologic indices including blood pressure, heart rate, respiratory rate, and
arterial oxygen saturation. The short-form of the Spielberger state anxiety
inventory, a visual analog scale well-being and cardiac monitoring devices were
used for collecting data. RESULTS: Patients exhibited a lower heart rate and
respiratory rate in the normal range during the 10-min visiting period and within
10 and 30 min after the visiting period. The arterial oxygen saturation increased
in this period. After the visiting period, patients exhibited an increase in the
sense of well-being and a decrease in the level of anxiety. CONCLUSION: Family
friend visits can improve MI patients' sense of well-being and decrease their
anxiety. Moreover, the visits can help to keep the physiological indices within
normal limits.
PMID- 25129884
TI - Effect of Rosa damascene aromatherapy on sleep quality in cardiac patients: a
randomized controlled trial.
AB - OBJECTIVE: Sleep disorders are common among patients hospitalized in coronary
care unit (CCU). This study aimed to investigate the effect of Rosa damascene
aromatherapy on sleep quality of patients hospitalized in CCU. METHODS: In this
randomized controlled trial, 60 patients who met the inclusion criteria were
conveniently sampled and randomly allocated to the experimental and control
groups. Patients in the control group received routine care. In the experimental
group, patients received routine care and Rosa damascene aromatherapy for three
subsequent nights. In the both groups the sleep quality was assessed using the
Pittsburgh Sleep Quality Index. RESULTS: After the study, the mean scores of five
domains of Pittsburg Sleep Quality Index as well as the mean of total score of
the index in the experimental group were significantly lower than the control
group. CONCLUSION: Rosa damascene aromatherapy can significantly improve the
sleep quality of patients hospitalized in CCUs.
PMID- 25129885
TI - Report on a membership audit of the Association of Chartered Physiotherapists in
Reflex Therapy (ACPIRT).
AB - Reflex Therapy (RT), akin to reflexology, is a non-invasive physiotherapy
modality approved by the UK Chartered Society of Physiotherapists. One hundred
members of the Association of Chartered Physiotherapists in Reflex Therapy
(ACPIRT) participated in an audit to establish a baseline of practice. Findings
indicate that experienced therapists use RT in conjunction with their
professional skills to induce relaxation (95%) and reduce pain (86%) for patients
with conditions including whiplash injury and chronic pain. According to 68% of
respondents, RT is "very good," "good" or "as good as" orthodox physiotherapy
practices. Requiring minimal equipment, RT may be as cost effective as orthodox
physiotherapy with regards to duration and frequency of treatment.
PMID- 25129883
TI - Trauma-sensitive yoga as an adjunct mental health treatment in group therapy for
survivors of domestic violence: a feasibility study.
AB - This study is a feasibility test of whether incorporating trauma-sensitive yoga
into group therapy for female victims of partner violence improves symptoms of
anxiety, depression, and posttraumatic stress disorder (PTSD) beyond that
achieved with group therapy alone. Seventeen (9 control, 8 intervention) adult
female clients seeking group psychotherapy were enrolled. A 12-week trauma
sensitive yoga protocol was administered once weekly for 30-40 min at the end of
each group therapy session. The control group received typical group
psychotherapy. Feasibility was assessed through recruitment and retention rates
as well as participants' self-reported perceptions of the safety and utility of
the study. The study enrolled 85% (17/20) of those screened eligible. Loss to
follow-up was 30% (5/17). No one reported emotional or physical harm. All of the
respondents reported that the study was personally meaningful and that the
results would be useful to others.
PMID- 25129886
TI - Reprogramming the genetic code in vitro.
AB - The site-specific introduction of non-canonical amino acids into polypeptides
through genetic code reprogramming has become a powerful tool for biochemical
studies and bioorganic synthesis. Although a variety of such techniques have been
developed, all are based on the 'mis-acylation' of tRNA molecules with non
canonical amino acids. Multiple strategies have been devised to synthesize such
non-canonical aminoacyl-tRNAs; for example, those based on protein or ribozyme
aminoacyl-tRNA synthetase enzymes are particularly useful. Such techniques have
enabled the incorporation of hundreds of different non-canonical amino acids into
polypeptides in vitro. This review discusses the development and application of
in vitro genetic code reprogramming techniques, especially enzymatic mis
acylation, and examines recent efforts to engineer the translational machinery to
increase the range of translatable non-canonical amino acids.
PMID- 25129888
TI - Disgust as a unique affective predictor of mental contamination following sexual
trauma.
AB - Mental contamination has been described as an internal experience of dirtiness
that can arise and persist in the absence of contact with observable physical
contaminants. Recent research has examined mental contamination specifically
related to unwanted physical contact and sexual trauma. This study evaluated the
degree to which disgust propensity and both self-focused and perpetrator-focused
peritraumatic disgust were associated with mental contamination in a sample of
women who experienced sexual trauma (n=72). Results showed that peritraumatic
self-focused disgust, but not peritraumatic perpetrator-focused disgust or fear,
was significantly associated with mental contamination. Additionally, disgust
propensity contributed significantly to the incremental validity of the model.
These findings support the nascent literature showing that disgust plays a
significant role in mental contamination, particularly following sexual trauma.
Future research directions, and clinical/theoretical implications of these
results are discussed.
PMID- 25129889
TI - The Cortical Signature of Central Poststroke Pain: Gray Matter Decreases in
Somatosensory, Insular, and Prefrontal Cortices.
AB - It has been proposed that cortical structural plasticity plays a crucial role in
the emergence and maintenance of chronic pain. Various distinct pain syndromes
have accordingly been linked to specific patterns of decreases in regional gray
matter volume (GMV). However, it is not known whether central poststroke pain
(CPSP) is also associated with cortical structural plasticity. To determine this,
we employed T1-weighted magnetic resonance imaging at 3 T and voxel-based
morphometry in 45 patients suffering from chronic subcortical sensory stroke with
(n = 23) and without CPSP (n = 22), and healthy matched controls (n = 31). CPSP
patients showed decreases in GMV in comparison to healthy controls, involving
secondary somatosensory cortex (S2), anterior as well as posterior insular
cortex, ventrolateral prefrontal and orbitofrontal cortex, temporal cortex, and
nucleus accumbens. Comparing CPSP patients to nonpain patients revealed a similar
but more restricted pattern of atrophy comprising S2, ventrolateral prefrontal
and temporal cortex. Additionally, GMV in the ventromedial prefrontal cortex
negatively correlated to pain intensity ratings. This shows for the first time
that CPSP is accompanied by a unique pattern of widespread structural plasticity,
which involves the sensory-discriminative areas of insular/somatosensory cortex,
but also expands into prefrontal cortex and ventral striatum, where emotional
aspects of pain are processed.
PMID- 25129890
TI - Factors contributing to home-based acceptability of rapid testing for HIV
infection among the inner city commuter population in Johannesburg, South Africa.
AB - BACKGROUND: The study aimed to determine factors contributing to the
acceptability of home-based HIV counselling and testing (HBHCT) among commuters
in Johannesburg inner city. METHODS: Simple random sampling was used to select
participants in a venue based intercept survey at Noord Street taxi rank in
Johannesburg central business district. A total of 1146 individuals were
interviewed and logistic regression analysis assessed factors associated with
HBHCT acceptability. RESULTS: HBHCT acceptability was 64%. Home testing was
preferred as an alternative to testing at a health facility. High school
education (adjusted odds ratio [aOR] 0.61, CI: 0.46-0.85), inner city residence
aOR 0.70, CI: 0.52-0.94), previous HIV testing in the hospital (aOR 0.22, CI:
0.15-0.32) and at home (aOR 0.18, CI: 0.11-0.27) were significantly less likely
associated with HBHCT acceptability. Being married (aOR 1.64, CI: 1.15-2.32),
recent HIV testing (aOR 1.85, CI: 1.15-2.99) and having experienced negative
health worker attitude (aOR 2.41, CI: 1.66-3.48) were significantly more likely
associated with HBHCT acceptability. CONCLUSIONS: High acceptability of HBHCT
among urban-based commuters plus factors that would deter HBHCT acceptability
were identified. Further research to identify strategies to improve HBHCT
acceptability among commuter populations is needed.
PMID- 25129891
TI - Childhood mortality and its association with household wealth in rural and semi
urban Burkina Faso.
AB - BACKGROUND: This study aimed to investigate the relationship between household
wealth and under-5 year mortality in rural and semi-urban Burkina Faso. METHODS:
The study included 15 543 children born between 2005 and 2010 in the Nouna Health
and Demographic Surveillance System. Information on household wealth was
collected in 2009. Two separate wealth indicators were calculated by principal
components analysis for the rural and the semi-urban households, which were then
divided into quintiles accordingly. Multivariable Cox proportional hazards
regression was used to study the effect of the respective wealth measure on under
5 mortality. RESULTS: We observed 1201 childhood deaths, corresponding to 5-year
survival probability of 93.6% and 88% in the semi-urban and rural area,
respectively. In the semi-urban area, household wealth was significantly related
to under-5 mortality after adjustment for confounding. There was a similar but
non-significant effect of household wealth on infant mortality, too. There was no
effect of household wealth on under-5 mortality in rural children. CONCLUSIONS:
Results from this study indicate that the more privileged children from the semi
urban area with access to piped water and electricity have an advantage in under
5 survival, while under-5 mortality in the rural area is rather homogeneous and
still relatively high.
PMID- 25129892
TI - Prediction of postoperative atrial fibrillation after cardiac surgery: light at
the end of the tunnel?
PMID- 25129893
TI - Phenylephrine in cardiac surgery: will it have a place?
PMID- 25129894
TI - Authors' reply: How much evidence is the evidence for a case report?
PMID- 25129887
TI - Absence of a simple code: how transcription factors read the genome.
AB - Transcription factors (TFs) influence cell fate by interpreting the regulatory
DNA within a genome. TFs recognize DNA in a specific manner; the mechanisms
underlying this specificity have been identified for many TFs based on 3D
structures of protein-DNA complexes. More recently, structural views have been
complemented with data from high-throughput in vitro and in vivo explorations of
the DNA-binding preferences of many TFs. Together, these approaches have greatly
expanded our understanding of TF-DNA interactions. However, the mechanisms by
which TFs select in vivo binding sites and alter gene expression remain unclear.
Recent work has highlighted the many variables that influence TF-DNA binding,
while demonstrating that a biophysical understanding of these many factors will
be central to understanding TF function.
PMID- 25129895
TI - Authors' reply.
PMID- 25129896
TI - US court invalidates Pfizer's Celebrex(r) patent.
PMID- 25129897
TI - Idenix files three patent infringement lawsuits in Europe.
PMID- 25129898
TI - Iroko pharmaeuticals announces patent for ZorvolexTM.
PMID- 25129899
TI - The evolution of the rubber endotracheal tube.
PMID- 25129900
TI - Jeanette Thirlwell: three decades of service to the Journal.
PMID- 25129901
TI - Education and training in ultrasound-guided neuraxial anaesthesia.
PMID- 25129902
TI - Screening for colorectal cancer and prostate cancer: challenges for New Zealand.
Richardson and Potter's reply.
PMID- 25129903
TI - Without rewards, the cycle of innovation would stop.
PMID- 25129904
TI - Charging what the market will bear is inappropriate.
PMID- 25129905
TI - Greater effectiveness for the same cost.
PMID- 25129906
TI - The system over-rewards incremental gains.
PMID- 25129907
TI - Impressive gains with innovative medicines.
PMID- 25129908
TI - Waste and missed opportunities drive costs upward.
PMID- 25129909
TI - Short-term costs can lead to long-term gain.
PMID- 25129910
TI - Eliminate cost-plus reimbursement for drugs.
PMID- 25129911
TI - [No methodological data? No comparable laboratory results].
PMID- 25129912
TI - [New antibiotics with activity against multidrug-resistant enterobacteriaceae.
Combination preparations are now being tested clinically].
PMID- 25129913
TI - [Point of care analyses are not used uniformly in primary health care. Equalis
survey shows that volume and the type of tests performed varies between different
health care centers].
PMID- 25129914
TI - [Swedish cooperation for genomic analyses of breast cancer tissue. Basis for
future individualized cancer treatment].
PMID- 25129915
TI - [Register studies measure the effectiveness of drugs in clinical practice. The
example PsoReg - redistribution of systemic treatment can increase the
efficiency].
PMID- 25129917
TI - [Freeze-dried plasma should be available for use in Swedish health care].
PMID- 25129916
TI - [Bleeding and surgery in the treatment with new oral anticoagulants. The
management can be complicated by the lack of specific antidotes].
PMID- 25129918
TI - [The GUCH example: A challenge to educate future "super specialists"].
PMID- 25129919
TI - ["There is no educational culture of in health care"].
PMID- 25129920
TI - [Statistical analysis improves medicine history research].
PMID- 25129921
TI - [Woody plant species composition and community structure in residual fragments of
broad-leaved Korean pine mixed forests in Changbai Mountains area].
AB - The broad-leaved Korean pine mixed forest represents the typical vegetation type
of the eastern mountain area in Northeast China. However, due to the interference
of human activities, the natural broad-leaved Korean pine forest only distributes
in some residual fragments with unequal areas in Changbai Mountains and Small
Hinggan Mountains. To compare and analyze the similarities and differences of
broad-leaved Korean pine mixed forests in the different areas, we established six
forest plots following the field protocol of the 50 hm2 forest plot in Panama
(Barro Colorado Island, BCI) in 2012 in Changbai Mountain National Nature Reserve
in Jilin Province and the eastern mountain area in Liaoning Province. All free
standing plant species with DBH (diameter at breast height) > or = 1 cm were
mapped, tagged and identified to species. The results showed that there were 69
woody species in the six plots, comprising 42 genera and24 families. Aceraceae
was the most species-rich family in all six plots. Most species belonged to the
plant type of North Temperate Zone, with a minor subtropical plant species
component. The statistics of species abundance, basal area, mean DBH, and
importance value showed that there were obviously dominant species in each
community. The DBH distribution of all individuals showed a reversed "J" type.
However, the percentage of individuals in small size-class and large size-class
varied in the six communities, which indicated that these communities were at
different successional stages. Ranked by the importance value, the DBH
distribution of the top three species in the six plots showed four distribution
types: reversed "J" distribution, reversed "L" distribution, unimodal
distribution, and partial peak distribution. Spatial distribution patterns of the
main species in the six plots changed differently with species and size-class,
and the distribution patterns of the same species varied in the different plots.
PMID- 25129922
TI - [Ecologically critical areas of broad-leaved Korean pine mixed forest in Changbai
Mountains, China].
AB - In order to improve the protection system to reduce the damage of biodiversity
and protect broad-leaved Korean pine mixed forest, 64 forest farms from 6
Forestry Bureaus around Changbai Mountains Nature Reserve were investigated and
analyzed. A total of 41 plants were selected as key protected plants, and felling
area, cropland, mining area, highway, railway and residential area were
considered as the disturbance factors. GAP and GIS spatial analysis were used to
draw the indicator plant and disturbance intensity distribution maps. The results
showed that the indicator species distribution was uneven. The indicator plant
enrichment regions were located on the north western and southern slopes centered
with Shengli and Lenggouzi forest farms of Quanyang County, respectively, and
single distributions of the endemic plants were found in Baoshan, Henshan,
Lenggouzi and Heishan forest farms. The different disturbance severities were
observed in the different forest farms, among which the north part in Lushuihe
and Baihe forest farms were severely disrupted. Two ecologically critical areas,
Quanyang-Lushuihe-Baihe on the north slope of Changbai Mountains and the east
part of Changbai County on the south slope, were determined based on the
comprehensive analysis.
PMID- 25129923
TI - [Variation of forest vegetation carbon storage and carbon sequestration rate in
Liaoning Province, Northeast China].
AB - The forest vegetation carbon stock and carbon sequestration rate in Liaoning
Province, Northeast China, were predicted by using Canadian carbon balance model
(CBM-CFS3) combining with the forest resource data. The future spatio-temporal
distribution and trends of vegetation carbon storage, carbon density and carbon
sequestration rate were projected, based on the two scenarios, i. e. with or
without afforestation. The result suggested that the total forest vegetation
carbon storage and carbon density in Liaoning Province in 2005 were 133.94 Tg and
25.08 t x hm(-2), respectively. The vegetation carbon storage in Quercus was the
biggest, while in Robinia pseudoacacia was the least. Both Larix olgensis and
broad-leaved forests had higher vegetation carbon densities than others, and the
vegetation carbon densities of Pinus tabuliformis, Quercus and Robinia
pseudoacacia were close to each other. The spatial distribution of forest
vegetation carbon density in Liaoning Province showed a decrease trend from east
to west. In the eastern forest area, the future increase of vegetation carbon
density would be smaller than those in the northern forest area, because most of
the forests in the former part were matured or over matured, while most of the
forests in the later part were young. Under the scenario of no afforestation, the
future increment of total forest vegetation carbon stock in Liaoning Province
would increase gradually, and the total carbon sequestration rate would decrease,
while they would both increase significantly under the afforestation scenario.
Therefore, afforestation plays an important role in increasing vegetation carbon
storage, carbon density and carbon sequestration rate.
PMID- 25129924
TI - [Estimating leaf area index of black locust (Robinia pseudoacacia L.) plantations
based on texture parameters of quickbird imagery].
AB - The black locust plantations located in Weibei area were chosen as research
objects and the texture parameters of different window sizes from high resolution
imagery were measured. Four different techniques, including simple linear
regression model, quadratic regression model, power model and exponential model,
were developed to describe the relationship between the texture parameters and
field measurements of LAI and to select the most effective texture parameters and
window size. The results showed that the texture parameters influenced the
accuracy of LAI estimation. Angular second moment and entropy index yielded
better adjust r2 than the other parameters. The r2 changed with the window size.
Dissimilarity and contrast index gained the largest r2 when the window size was
9x9. The r2 of the other texture parameters reduced as the window size increased
and a window size of 3 x 3 was more successful than any of the others. Power
equation performed poorest than the other three techniques for estimation of LAI.
PMID- 25129925
TI - [Effects of simulated nitrogen deposition on growth and phosphorus efficiency of
Pinus massoniana under low phosphorus stress].
AB - Atmospheric nitrogen (N) deposition dramatically raised in recent decades,
resulting in increases of soil N availability and N/P ratio, which would impact
plant growth and P efficiency under low P stress. Taking breeding population of
Pinus massoniana as test materials, a pot experiment was conducted to simulate
two P conditions, i. e., homogeneous low P availability vs. heterogeneous low P
among soil layers, in combination with two N deposition levels on growth traits
and P absorption and utilization efficiency of P. massoniana. Under the
homogeneous low phosphorus condition, growth traits and P efficiency of P.
massoniana were not significantly improved by simulated nitrogen deposition, but
significant nitrogen x family interaction effect was detected, with the biomass
of family 40x44 and 71x20 being increased, 36x29 and 73x23 being decreased. Under
the heterogeneous low P condition, significant N effects on the seedling height,
biomass and P absorption efficiency were observed, due to promoted root length
and root distribution ratio of topsoil. In addition, the effects of simulated N
deposition on growth and P efficiency of P. massoniana were relevant to the N/P
ratio. Under the homogeneous low P condition, the N/P ratio of P. massoniana
plant was 13.8, plants exhibited a low sensitivity to simulated N deposition,
root secreted APase activity was increased but the plant growth was not promoted.
In comparison, the plant N/P ratio was 9.7 under the heterogeneous low P
condition, and the plant growth and P efficiency were significantly promoted,
while no obvious change occurred in root secreted APase activity.
PMID- 25129926
TI - [Changes in vegetation and soil characteristics under tourism disturbance in
lakeside wetland of northwest Yunnan Plateau, Southwest China].
AB - The characteristics of vegetation and soil were investigated in Bita Lake and
Shudu Lake wetlands in northwest Yunnan Plateau under tourism disturbance. The 22
typical plots in the wetlands were classified into 4 types by TWINSPAN, including
primary wetland, light degradation, moderate degradation, and severe degradation.
Along the degradation gradient, the plant community density, coverage, species
number and Shannon diversity index increased and the plant height decreased in
Bita Lake and Shudu Lake wetlands, and Whittaker diversity index increased in
Bita Lake wetland. Plant species number, soil organic matter, total nitrogen,
porosity, available nitrogen, available phosphorus and available potassium
contents were higher in Shudu Lake wetland than in Bita Lake wetland, but the
plant density, height, soil total potassium and pH were opposite. Canonical
correspondence analysis (CCA) by importance values of 42 plants and 11 soil
variables showed that soil organic matter, total nitrogen and total potassium
were the key factors on plant species distribution in Bita Lake and Shudu Lake
wetlands under tourism disturbance. TWINSPAN classification and analysis of
vegetation-soil characteristics indicated the effects of tourism disturbance in
Bita Lake wetland were larger than in Shudu Lake wetland.
PMID- 25129927
TI - [Effects of snow pack on soil nitrogen transformation enzyme activities in a
subalpine Abies faxioniana forest of western Sichuan, China].
AB - This study characterized the dynamics of the activities of urease, nitrate
reductase and nitrite reductase in both soil organic layer and mineral soil layer
under three depths of snow pack (deep snowpack, moderate snowpack and shallow
snowpack) over the three critical periods (snow formed period, snow stable
period, and snow melt period) in the subalpine Abies faxoniana forest of western
Sichuan in the winter of 2012 and 2013. Throughout the winter, soil temperature
under deep snowpack increased by 46.2% and 26.2%, respectively in comparison with
moderate snowpack and shallow snowpack. In general, the three nitrogen-related
soil enzyme activities under shallow snowpack were 0.8 to 3.9 times of those
under deep snowpack during the winter. In the beginning and thawing periods of
seasonal snow pack, shallow snowpack significantly increased the activities of
urease, nitrate and nitrite reductase enzyme in both soil organic layer and
mineral soil layer. Although the activities of the studied enzymes in soil
organic layer and mineral soil layer were observed to be higher than those under
deep- and moderate snowpacks in deep winter, no significant difference was found
under the three snow packs. Meanwhile, the effects of snowpack on the activities
of the measured enzymes were related with season, soil layer and enzyme type.
Significant variations of the activities of nitrogen-related enzymes were found
in three critical periods over the winter, and the three measured soil enzymes
were significantly higher in organic layer than in mineral layer. In addition,
the activities of the three measured soil enzymes were closely related with
temperature and moisture in soils. In conclusion, the decrease of snow pack
induced by winter warming might increase the activities of soil enzymes related
with nitrogen transformation and further stimulate the process of wintertime
nitrogen transformation in soils of the subalpine forest.
PMID- 25129928
TI - [Effects of drought stress on growth and water use efficiency of two medicinal
plants].
AB - Growth characteristics, stable carbon isotope discrimination (Delta13C), water
use efficiency (WUE), and their correlation of Cassia obtusifolia and Isatis
indigotica were measured at three soil water levels, i. e., 30%, 50% and 75% of
field water holding capacity (FWHC), and at three growth stages. The growth
indices of the two medicinal plants at 75% of FWHC were higher than those at 30%
and 50% of FWHC, suggesting that the two medicinal plants could obtain high
production under sufficient moisture condition. The Delta13C(A) (aboveground
biomass-based Delta13C) and Delta13C(T) (total biomass-based Delta13C) decreased,
and the WUE(A) (aboveground biomass-based WUE) and WUE(T) (total biomass-based
WUE) of C. obtusifolia and I. indigotica increased with the increasing degree of
drought stress. The growth indices of the two medicinal plants had little
difference in the different water treatments, which indicated that the two
medicinal plants were insensitive to drought stress. Water use efficiency of I.
indigotica had significant negative relationships with aboveground biomass and
total biomass, while that of C. obtusifolia had a significant positive
correlation with the root/shoot ratio.
PMID- 25129929
TI - [Effects of stand structure regulation on soil labile organic carbon in Pinus
elliottii plantation].
AB - Taking 21-year-old Pinus elliottii pure plantation as the control, effects of
enrichment planting with broadleaf trees (Liquidambar fornosana) after thinning
the conifer trees (P. elliottii) on soil labile organic carbon of different
plantations, including 3-year-old, 6-year-old, 9-year-old P. elliottii and 21
year-old P. elliottii-L. fornosana mixed plantations, were investigated. The
results showed that the contents of soil dissolved organic carbon (DOC), readily
oxidizable organic carbon (ROC), and microbial biomass carbon (MBC) significantly
increased in the 6-year-old and 9-year-old plantations compared with those in the
21-year-old P. elliottii pure plantation. Soil labile organic carbon contents in
the 21-year-old P. elliottii-L. fornosana mixed plantation increased
significantly than those in 3-year-old, 6-year-old, 9-year-old stands, and the
DOC, ROC and MBC contents increased by 113.1%, 53.3% and 54.6%, respectively,
compared with those in the 21-year-old P. elliottii pure plantation. The results
suggested that replanting with broadleaf trees are an effective measure to
improve the soil ecological function in pure P. elliottii plantation.
PMID- 25129930
TI - [Community structure and distribution of riparian Bambusa rigida along lower
Gongjiang River, China].
AB - The community structure and distribution of secondary riparian Bambusa rigida in
lower Gongjiang River were studied by the transect sampling method and reverse
age-class addition. The species in tree and shrub layers in the riparian B.
rigida community had the strong native trait. Along the river gradient, the
associated species in tree and shrub layers were fragmented, and associated with
shore highland plants, suggesting that their distribution did not meet the RCC
theory of continuous riparian law. Plant species in herb layer was in accordance
with the RCC law, and the species abundance in lower reach was the greatest with
29 families, 55 genera, and 70 species. B. rigida was absolutely dominant in the
riparian communities and adapted to the regulation of tree density and
physiological integration. The proliferation ratio of B. rigida rapidly decreased
to become stabilized, and the degree of its clump dispersion pattern gradually
increased. The average density of secondary riparian B. rigida was 114-141 bamboo
trees per clump, and the community was in the mid- and late succession stage.
PMID- 25129931
TI - [Root system distribution and biomechanical characteristics of Bambusa oldhami].
AB - To determine the mechanism of soil stabilizing through Bambusa oldhami root
system, the vertical distribution of B. oldhami root system in soil was
investigated, and the tensile strength of individual root and soil shear strength
were measured in B. oldhami forest. The dry mass, length, surface area and volume
of the B. oldhami root system decreased with the increasing soil depth, with more
than 90% of the root system occurring in the 0-40 cm soil layer. The root class
with D 1 mm occupied the highest percentage of the total in terms of root length,
accounting for 79.6%, but the lowest percentage of the total in terms of root
volume, accounting for 8.2%. The root class with D >2 mm was the opposite, and
the root class with D= 1-2 mm stayed in between. The maximum tensile resistance
of B. oldhami root, either with 12% moisture content or a saturated moisture
content, increased with the increasing root diameter, while the tensile strength
decreased with the increasing root diameter in accordance with power function.
Tensile strength of the root, with either of the two moisture contents, was
significantly different among the diameter classes, with the highest tensile
strength occurring in the root with D < or = 1 mm and the lowest in the root with
D > or = 2 mm. The tensile strength of root with 12% moisture content was
significantly higher than that with the saturated moisture content, and less
effect of moisture content on root tensile strength would occur in thicker roots.
The shear strengths of B. oldhami forest soil and of bare soil both increased
with the increasing soil depth. The shear strength of B. oldhami forest soil had
a linear positive correlation with the root content in soil, and was
significantly higher than that of bare soil. The shear strength increment in B.
oldhami forest was positively correlated with the root content in soil according
to an exponential function, but not related significantly with soil depth.
PMID- 25129932
TI - [Adaptability analysis of FAO Penman-Monteith model over typical underlying
surfaces in the Sanjiang Plain, Northeast China].
AB - It is very important for studying surface energy and water balance to improve the
accuracy of evapotranspiration (ET) estimation. Based on eddy covariance
measurements and microclimate observational data available, comparisons were done
in accuracy of simulating ET with the FAO Penman-Monteith model from the
marshland, rice paddy and soybean field in the Sanjiang Plain. The results showed
that the values of ET simulated with the model over marshland was significantly
higher than the measured one (averagely 81.8% higher) when the crop coefficients
recommend by FAO were adopted, and its modeling efficiency was negative, which
indicated that the ET from the marshland couldn' t be simulated by the model.
While the seasonal variation of ET over rice paddy and soybean field could be
simulated by the model and the accuracy in simulating ET from rice paddy was
better than that from soybean field. Crop coefficients (Kc) of marshland, rice
paddy and soybean field were all significantly positively related to leaf area
index, and crop coefficient of soybean field was also significantly negatively
related to vapor pressure deficit. With Kc modified through linear regression,
the FAO Penman-Monteith model markedly improved the estimation accuracy for
marshland, rice paddy and soybean field, with the mean bias error ranging from
0.1 to 0.3 mm x d(-1), root mean square error ranging from 0.50 to 0.67 mm x d(
1) and modeling efficiency ranging from 0.69 to 0.85. Still, the accuracy in
simulating ET from rice paddy was superior to that from the other two underlying
surfaces. The FAO Penman-Monteith model was suitable to simulate the ET from rice
paddy whether the crop coefficient was modified or not. However, the crop
coefficient must be modified if the model was used to simulate the ET from
marshland and soybean field.
PMID- 25129933
TI - [Effects of irrigation amount on morphological characteristics and water use of
Jatropha curcas].
AB - Jatropha curcas is the most promising energy tree, and soil moisture is the key
factor which affects the seedling quality and water use efficiency of J. curcas.
With aims to evaluate the effect of different irrigation amount on growth,
morphological characteristics and water use of J. curcas, a pot experiment was
conducted with four irrigation amounts, i. e., W1:472.49 mm, W2: 228.79 mm,
W3:154.18 mm and W4:106.93 mm, respectively. Compared with W1 treatment, the leaf
area and stem cross-section area of base significantly decreased in W2, W3 and W4
treatments, but Huber value significantly increased, which could improve the
efficiency of water transfer from root to shoot, thus enhance the capability of
resistance to drought stress. Compared with W, treatment, the healthy index of J.
curcas seedlings decreased slightly in W2 treatment but significantly decreased
in W3 and W4 treatments. Hence, the irrigation amount from 228.79 to 472.49 mm
was beneficial to increase the healthy index of J. curcas seedlings. Compared
with W1 treatment, irrigation water was saved by 67.4% in W3 treatment, and the
total dry mass and evapotranspiration significantly decreased by 17.4% and 68.6%,
and the irrigation water use efficiency and total water use efficiency increased
by 153.2% and 163.2%, respectively. In the condition of this study, the
irrigation amount of 154.18 mm was beneficial to increase water use efficiency.
PMID- 25129934
TI - [Characteristics of soil organic carbon mineralization at different temperatures
in paddy soils under long-term fertilization].
AB - Dynamics of soil organic carbon mineralization affected by long-term
fertilizations and temperature in relation to different soil carbon fractions
were investigated in paddy soils. Soil samples were collected from the plough
layer of 3 long-term national experimental sites in Xinhua, Ningxiang and
Taojiang counties of Hunan Province. Mineralization of soil organic C was
estimated by 33-day aerobic incubation at different temperatures of 10, 20 and 30
degrees C. The results showed that the rates of CO2 production were higher during
the earlier phase (0-13 d) in all treatments, and then decreased according to a
logarithm function. Higher incubation temperature strengthened C mineralization
in the different treatments. The quantities of cumulative CO2 production in NPK
with manure or straw treatments were greater than in inorganic fertilizers
treatments. The Q10 values in the different soil treatments ranged from 1.01
1.53. There were significantly positive correlations between the Q10 values and
soil total organic carbon (TOC), easy oxidation organic carbon (EOOC), humic acid
carbon (C(HA)), fulvic acid carbon (CFA). The cumulative amount of mineralized C
was significantly positively correlated with microbial biomass carbon (MBC) at 10
and 20 degrees C, but not significantly at 30 degrees C. Significant correlations
were found between the cumulative amount of mineralized C and different soil
carbon fractions and C(HA)/C(FA). The correlations of differ- ent soil carbon
fractions with the ratio of cumulative mineralized C to TOC were negatively
correlated at 10 degrees C, but not significantly at 20 and 30 degrees C. These
results suggested that the application of NPK with manure or straw would be
helpful to increase the sequestration of C in paddy soils and reduce its
contribution of CO2 release in the atmosphere.
PMID- 25129935
TI - [Impacts of nighttime warming on rice growth stage and grain yield of leading
varieties released in different periods in Jiangsu Province, China].
AB - A field experiment was conducted to investigate the actual impacts of nighttime
warming on rice growth stage and grain yield in Danyang, Jiangsu Province, with 8
leading varieties approved and released during 1970s-2000s. The field was warmed
at nighttime for an entire growth stage (i. e. sown date to harvest) with a Free
Air Temperature Increase (FATI) facility. The results showed that there were
significant differences in the extents of warming impact on rice growth stage and
grain yield among the leading varieties, though the impact trends were similar.
An increase of 0.9 degrees C in nighttime mean temperature in rice canopy could
shorten the length of rice entire growth stage by 1.3 d. Nighttime warming tended
to decrease post-anthesis green leaves area and the flag leaf area, and to
decline rice aboveground biomass production and grain yield by 3.5% and 5.1%,
respectively. Meanwhile, nighttime warming decreased the plant nitrogen
concentration at maturity. Nighttime warming reduced the grain yield mainly
through decreasing the effective panicles and grain numbers per panicle. There
was no stable changing trend in the differences in warming impacts on the
varieties released in the different periods.
PMID- 25129936
TI - [Effects of all-day warming on growth, development and yield of winter wheat
cultivars bred in different periods].
AB - A field experiment was conducted to study the effects of all-day warming on the
growth, development and yield of winter wheat cultivars bred in different periods
under free air temperature increase (FATI) in Xuzhou and Danyang, Jiangsu
Province. Warming decreased the effective tillers by 5.2% and 9.6%, and the
ineffective tillers by 15.6% and 9.7% in Xuzhou and Danyang, respectively. Plant
height under FATI was higher in Xuzhou, but lower in Danyang than that of the
control. Plant heights of the late cultivars were lower than that of the early
cultivars. Warming increased the leaf area index for all cultivars. Warming
increased the net photosynthetic rates of the winter wheat cultivars except for
those bred in 1950-1960s and 1980s in Xuzhou and 1950-1960s and 1990s in Danyang.
There were different changing tendencies of the night respiration rate among the
winter wheat cultivars bred in different periods. Aboveground biomass and harvest
index of all cultivars increased under FATI. Harvest index of late cultivars was
higher than that of early cultivars in Xuzhou and Danyang. Growth period of
different cultivars under FATI was all shortened, av- eragely by 3.2 and 4.1 d in
Xuzhou and Danyang, respectively, mainly due to shortening the preheading stage
(averagely by 7.5 and 8.5 d in Xuzhou and Danyang, respectively) and prolonging
the filling stage (by average 4.3 d). Except for 1950-1960s cultivars in Xuzhou,
the grain yields increased under FATI, averagely by 21.0% and 14.1% in Xuzhou and
Danyang, respectively. Statistical analysis of variance showed that the warming
induced wheat yield changes were due to the changes in grain number per spike and
effective spikes in Xuzhou and the change in 1000-grain mass in Danyang,
respectively.
PMID- 25129937
TI - [Effects of N and S application on grain filling characteristics and yield of
winter wheat].
AB - A field experiment was conducted on the Guanzhong Plain, China, to evaluate the
effects of N and S application on characteristics of winter wheat (cv. Xiaoyan
22) grain filling and yield, using a central composite rotatable design with two
factors nitrogen (N) and sulfur (S). The results showed that, with the combined
application of N and S, grain filling followed a "S" curve which increased slowly
at first, then quickly, and then slowly again. With 108 and 267 kg N x hm(-2),
the grain fill duration, theoretical maximum grain yield, and average filling
rate decreased as the S application rate increased. With 97.5 and 202.5 kg S x
hm(-2), N application improved grain filling parameter values. With 187.5 kg N x
hm(-2) or 150 kg S x hm(-2), the parameters firstly increased, reached a maximum,
and then decreased as the S or N input increased. Grain filling rate increased
for 25 days following anthesis, and then declined at a rate that varied among
treatments. When the N input was > 187.5 kg x hm(-2) or the S input was > 150 kg
x hm(-2), the grain filling rate decreased with increasing the S or N input. The
results also indicated that combined application of N and S fertilizers at
appropriate rates could increase the head density and grain yield. Using the
regression equations, highest grain yields estimates (> or = 3753 kg x hm(-2))
were achieved with the combination of a high N rate (178.31-256.36 kg x hm(-2))
and a moderate S rate (131.95-167.65 kg x hm(-2)).
PMID- 25129938
TI - [Effects of shading on endogenous hormones regulation in kernel development of
summer maize in the field].
AB - Taking 3 maize hybrids, Zhenjie 2 (ZJ2), Denghai 605 (DH605) and Zhengdan 958
(ZD958) as test materials, the effects of shading on the physiological function
of endogenous hormones during grain formation of summer maize were investigated
in the field. The ambient sunshine treatment was used as the control (CK) and 3
shading treatments with a shading degree of 60% were designed in growth periods
ranging from tasseling to maturity (S1), from jointing to tasseling stage (S2)
and whole growing period (S3), respectively. Results showed that the total floret
number, filament number and pollination floret number decreased after shading in
comparison with CK, and aborted seeds increased accordingly. The kernels per ear
showed an order of CK > S2 > S > S3, and those of S1, S2 and S3 were 18.9%, 43.7%
and 80.8% lower than that of CK. The IAA, GA and ZR contents of normal grain in
the shading treatments were lower than in CK, while the ABA content was opposite.
The same hormone change with grain growth in all treatments presented a similar
trend. Compared to normal grains, the maximum value of IAA content in aborted
grains shifted from the 20th day to the 10th day after pollination, with less IAA
accumulation and rapid reduction, and the contents of GA and ZR decreased
significantly, while that of ABA was still high at the 20th day after
pollination. Therefore, the effects of shading on hormone contents in grains
might lead to grain abortion and yield reduction.
PMID- 25129939
TI - [Effects of high temperature and humidity stress at the physiological maturity
stage on seed vigor, main nutrients and coat structure of spring soybean].
AB - A pot experiment was conducted to investigate the effects of high temperature and
humidity stress [(40 +/- 2) degrees C/(30 +/- 2) degrees C, RH (95 +/- 5)%/(70 +/
5)%, 10 h/14 h (day/night)] at the physiological maturity stage of two spring
soybean cultivars (Xiangdou No. 3 and Ningzhen No. 1) on seed vigor indices, main
nutritional components and coat anatomical structure. High temperature and
humidity stress were found to cause the decrease of seed viability, germination
potential, and germination percentage as well as the dehydrogenase and acid
phosphatase activities, but increased the seed cell membrane permeability as well
as H+, soluble sugar and leucine levels in the seed soaking liquid of each
cultivar. Moreover, the stress led to irregular changes of seed oil and protein
contents and alteration of anatomical structure of episperm and hilum in the two
cultivars. A shortterm stress (less than 5 h) had no significant impact on seed
vigor, but a long-term one (more than 48 h) caused rapid decrease of seed vigor
indices. Xiangdou No. 3 showed less decreases in seed germination potential and
enzyme activities, and less increase in extravasation content in the seed soaking
liquid, had compact seed coat and intact hilum, suggesting it was more resistant
to high temperature and humidity stress.
PMID- 25129940
TI - [Effects of root cutting under different seedling conditions on root system
distribution and senescence character of peanut].
AB - The effects of root cutting on root system distribution and senescence character
of peanut (Arachis hypogaea) under different seedling conditions were
investigated by using the box culture method. The results showed that, with three
types of peanut seedlings, including overgrowing, strong and week seedlings, root
cutting all first restricted and then promoted the root system growth, especially
promoted the root growth to deep soil. This effect was stronger on the
overgrowing and strong seedlings, while relatively weaker on the weak seedlings.
After root cutting, root activity, superoxide dismutase (SOD) and peroxidase
(POD) activity all reduced at first, and then increased, compared with each
control. The extents of decrease in root activity, SOD and POD activity were
highest in the weak seedlings, lowest in the overgrowing seedlings, and moderate
in the strong seedlings. However, in the later stage after root cutting, the
extents of increase in root activity, SOD and POD activity were higher in the
overgrowing and strong seedlings, than in the weak seedlings. Generally, root
cutting could promote the root activity of peanut and delay the senescence.
PMID- 25129941
TI - [Effects of exogenous silicon on physiological characteristics of cucumber
seedlings under ammonium stress].
AB - The present study evaluated the effects of exogenous silicon on growth and
physiological characteristics of hydroponically cultured cucumber seedlings under
ammonium stress. The results showed that the growth, especially the aerial part
growth of cucumber seedlings cultured with ammonium were significantly inhibited
than those with nitrate, especially after treatment for 10 d, the aerial part
fresh mass of cucumber seedlings were reduced 6.17 g per plant. The accumulation
of reactive oxygen species (ROS) was also promoted in cucumber seedlings under
ammonium, and the contents of O2*- and H2O2 were significantly increased in
cucumber leaves. With the exogenous silicon treatment, the activities of
superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate
peroxidase (APX) were significantly improved, the ability to remove reactive
oxygen species was enhanced, the contents of O2*- and H2O2 were significantly
reduced in cucumber leaves, decreasing the reactive oxygen damage to the cell
membrane, and the ratio of electrolyte leakage and the content of MDA in cucumber
leaves. Also, with exogenous silicon treatment, the plasma membrane and activity
of vacuolar membrane H(+)-ATP was significantly increased, transport capacity of
intracellular proton was improved, and the level of ammonium in cucumber body was
significantly reduced, thereby reducing the toxicity of ammonium. In conclusion,
exogenous silicon could relieve ammonium stress, by increasing the antioxidant
enzyme activity, H(+)-ATP activity, and decreasing the ammonium content in
cucumber seedlings.
PMID- 25129942
TI - [Effects of nutrition medium on cucumber growth and soil microenvironment in
greenhouse under continuous cropping].
AB - An experiment of continuous cropping of cucumber in nutrition medium (composted
with straw, rural soil and puffed chicken manure) or soil was conducted in
greenhouse in order to study the effects of medium type on the cucumber growth
and soil microenvironment, respectively. The results showed that the two
treatments both displayed different levels of obstacles resulted from continuous
cropping. In the same cropping season, the nutrient content, soil invertase and
urease activities and B/F (bacteria/fungi) ratio in the nutrition medium were
obviously higher but fungi quantity was lower than in the soil medium, suggesting
the use of nutrition medium changed the bacterial population structure as to
improve the cucumber growth and yield. Under continuous cropping, correlation
analysis showed that the bacterial quantity was significantly positively related
with plant height and root dry mass, and markedly significantly positive
correlation exited between the aboveground dry mass and yield of cucumber. The
urease activity was also significantly positively related with the cucumber
yield. Compared with the soil medium, the nutrition medium could greatly improve
soil microenvironment and alleviate the continuous cropping obstacle.
PMID- 25129943
TI - [Optimal nighttime temperature for tomato plant in greenhouse in autumn and
winter].
AB - In order to investigate the effect of nighttime temperature (NT) on adult stage
tomato plants in greenhouse, an experiment was conducted by using natural light
growth chamber. Tomato plants were treated with 4 nighttime temperature as
natural NT (CK), 14, 16, and 18 degrees C, on condition of the same daytime
temperature (DT). Actual NT of CK, 14, 16, and 18 degrees C treatments were 13.1,
13.4, 14.7, and 16.3 degrees C, respectively. Physiological response,
photosynthesis, dry matter accumulation and production of tomato plant under
different NT treatments were determined. The results showed that, tomato plants
under CK treatment suffered lower temperature press periodically, and the
membrane system was damaged to some extent, resulting in the lowest dry matter
accumulation and nearly no early yield (28 g mature fruit per plant). Compared
with CK, dry matter accumulation of tomato plant under 14 degrees C treatment was
increased significantly, early yield was 304 g per plant, and total production
was increased by 58% (immature fruit included). As for the 18 degrees C
treatment, the net photosynthetic rate (Pn) of tomato plant was significantly
increased by 10.6%-12.5%, dry matter accumulation was increased by 26%, flower
time was advanced by 4-12 days, fruit number per plant was 3.8, fresh matter per
fruit was increased by 42.7 g, early yield per plant was 476 g, and the total
production per plant was increased by 101%. All the items under 16 degrees C
treatment were between those under 14 degrees C and 18 degrees C treatments.
Therefore, at DT of 22 degrees C, the low NT limit was 13.4 degrees C and the
optimal NT should be above 16.3 degrees C for greenhouse tomato plants in autumn
and winter in North China.
PMID- 25129944
TI - [Effect of shifting sand burial on evaporation reduction and salt restraint under
saline water irrigation in extremely arid region].
AB - The Taklimakan Desert Highway Shelterbelt is drip-irrigated with high saline
groundwater (2.58-29.70 g x L(-1)), and shifting sand burial and water-salt
stress are most common and serious problems in this region. So it is of great
importance to study the effect of shifting sand burial on soil moisture
evaporation, salt accumulation and their distribution for water saving, salinity
restraint, and suitable utilization of local land and water resources. In this
study, Micro-Lysimeters (MLS) were used to investigate dynamics of soil moisture
and salt under different thicknesses of sand burial (1, 2, 3, 4, and 5 cm), and
field control experiments of drip-irrigation were also carried out to investigate
soil moisture and salt distribution under different thicknesses of shifting sand
burial (5, 10, 15, 20, 25, 30, 35, and 40 cm). The soil daily and cumulative
evaporation decreased with the increase of sand burial thickness in MLS,
cumulative evaporation decreased by 2.5%-13.7% compared with control. And
evaporative inhibiting efficiency increased with sand burial thickness,
evaporative inhibiting efficiency of 1-5 cm sand burial was 16.7%-79.0%. Final
soil moisture content beneath the interface of sand burial increased with sand
burial thickness, and it increased by 2.5%-13.7% than control. The topsoil EC of
shifting sand in MLS decreased by 1.19-6.00 mS x cm(-1) with the increasing sand
burial thickness, whereas soil salt content beneath the interface in MLS
increased and amplitude of the topsoil salt content was higher than that of the
subsoil. Under drip-irrigation with saline groundwater, average soil moisture
beneath the interface of shifting sand burial increased by 0.4% -2.0% compare
with control, and the highest value of EC was 7.77 mS x cm(-1) when the sand
burial thickness was 10 cm. The trend of salt accumulation content at shifting
sand surface increased firstly, and then decreased with the increasing sand
burial thickness. Soil salt contents beneath the interface of shifting sand
burial were much lower than that of shifting sand surface. 35 cm was the critical
sand burial thickness for water-saving and salt restraint. In summary, sand
burial had obvious inhibition effects on soil evaporation and salt accumulation,
so maybe it could be used to save water and reduce salt accumulation in arid
shifting desert areas.
PMID- 25129945
TI - [Quantitative analysis of the built-up area expansion in Su-Xi-Chang region,
China].
AB - Based on RS-derived maps and socio-economic statistics, this paper analyzed the
spatiotemporal dynamic pattern and driving mechanism of built-up area expansion
in Su-Xi-Chang region from 1990 to 2010. 3S-based spatial analysis techniques
were used, landscape expansion indices were calculated, and multiple stepwise
regression models were also used. In the past 20 years, the built-up area had
experienced rapid-moderate-accelerating expansion stages, which was strongly
affected by the national development strategies and policies regarding land use.
During the study period, the built-up area had increased by 2218.9 km2 mainly due
to the encroaching from paddy field, dryland and artificial ponds. From 1990
1995, the pattern of built-up area expansion was dominated by the infilling and
edge-expansion type; from 1995-2000, the outlying-type had overplayed infilling
and edge-expansion types due to policy restrictions on the latter; after 2000,
the outlying-type growth had decreased by a large extent, whereas the infilling
mode had increased dramatically, which resulted in the spatially compact pattern
of the newly built-up area. The increase of urban population and the boom of
regional economy were the major driving forces of built-up area expansion. The
study implied that improvements were urgently needed in land management system
and high-efficiency use of cropland. Promoting the compact development of built
up area was also crucial for striving toward regional sustainability.
PMID- 25129946
TI - [Evaluation of ecosystem service values of the forests of Shennongjia Nature
Reserve].
AB - As an ecological protected area for rare animals and plants in a subtropical
forest zone, Shennongjia National Reserve plays an important role in the study of
biodiversity in China. By using the market value, shade-price and opportunity
cost methods, the forest ecosystem service values of Shennongjia National Nature
Reserve were evaluated, including forest production, recreation and culture,
water conservation, soil conservation, gas regulation, environment purification,
nutrient circulation and biodiversity conservation. The total value of the
Shennongjia Nature Reserve was approximately 204.33 x 10(8) yuan RMB x a(-1). The
values of the different functions were in order of biodiversity conservation
(68.5%) > soil conservation (12.7%) > recreation and culture (4.9%) > gas
regulation (4.8%) > forest production (4.2%) > water conservation (3.9%) >
environment purification (0.7%) > nutrient circulation (0.3%). The values with
respect to utility were in sequence of unused value (68.5%) > indirect value in
use (22.4% ) > direct value in use (9.1%).
PMID- 25129947
TI - [Responses of ecosystem services value to land use change in national nature
reserves in Xinjiang, China].
AB - With GIS and RS technology, characteristics of land use change and ecosystem
services value of different years in six national nature reserves in Xinjiang,
China were analyzed with remote sensing image of the year 2000-2010. Results
showed that the area of water body and grassland decreased while the area of
forest, farmland, wetland, unused land and construction land increased in 2000
2010. Variation rate of land use change in 2000-2005 was faster, as 2.4-6.3 times
as that in 2005-2010. The total ecosystem services value mostly consisted of that
of water body, grassland and forest, accounting for 93% approximately. During the
study, the values of all kinds of the ecosystem services increased except for
grassland and water body, the total ecosystem services value increased firstly
and then decreased, and overall emerged as a reducing trend with the rate of
1.2%. In the process of the development of the west regions, it is necessary to
pay more attention to the protection of natural resources and ecosystem
restoration, so as to achieve sustainable development of resources, environment
and social economy in the western regions.
PMID- 25129948
TI - [Evaluation of wetland ecological benefit and restoration in the natural reserves
of western Jilin Province, China].
AB - In order to correctly evaluate wetland ecological benefit and restoration in the
natural reserves of western Jilin Province, an index system of wetland ecological
benefit assessment for nature reserves was established based on ecosystem service
theory and catastrophe theory. Considering the diversity characteristics of
ecological benefit, and consulting the research results of ecological benefit in
study area in 2001, the analytic hierarchy process and entropy method were
introduced to analyze the ecological benefit and restoration in 2005 and 2012.
The results showed that the ecological benefit level was very high in Momoge
Nature Reserve since 2005, high in Chaganhu and Xianghai nature reserves, and
moderate in Dabusu Nature Reserve. This study showed that the assessment
combining the catastrophe progression method with the analytic hierarchy process
and entropy method could reveal the dynamics and the integrality of wetland
ecological benefit, and accurately reflect the reality of the ecological
restoration in study area. In recent years, some achievements in ecological
protection and environmental remediation had been obtained in the west of Jilin
Province, and the whole ecological benefit of the wetlands had been improved and
enhanced by means of man-made effective interference.
PMID- 25129949
TI - [System construction of early warning for ecological security at cultural and
natural heritage mixed sites and its application: a case study of Wuyishan
Scenery District].
AB - This paper proposed a new concept of ecological security for protection by a
comprehensive analysis of the contents and standards of world heritage sites. A
frame concept model named "Pressure-State-Control" for early warning of
ecological security at world heritage mixed sites was constructed and evaluation
indicators of this frame were also selected. Wuyishan Scenery District was chosen
for a case study, which has been severely disturbed by natural and artificial
factors. Based on the frame model of "Pressure-State-Control" and by employing
extension analysis, the matter-element model was established to assess the
ecological security status of this cultural and natural world heritage mixed
site. The results showed that the accuracy of ecological security early warning
reached 84%. Early warning rank was I level (no alert status) in 1997 and 2009,
but that in 2009 had a higher possibility to convert into II level. Likewise, the
early-warning indices of sensitive ranks were different between 1997 and 2009.
Population density, population growth rate, area index for tea garden, cultivated
land owned per capita, level of drought, and investment for ecological and
environmental construction were the main limiting factors to hinder the
development of ecological security from 2009 to future. In general, the status of
Wuyishan Scenery District ecological security was relatively good and considered
as no alert level, while risk conditions also existed in terms of a few early
warning indicators. We still need to pay more attention to serious alert
indicators and adopt effective prevention and control measures to maintain a good
ecological security status of this heritage site.
PMID- 25129950
TI - [Effects of bacterial consortium EG03 on control of pepper bacterial wilt and
rhizosphere microbial community characteristics in fields].
AB - Bacterial consortium EG03, consisted of several different antagonistic bacteria
against Ralstonia solanacearum, was demonstrated to efficiently control bacterial
wilt of pepper in field with a biocontrol efficacy of 85.8%. The traditional
dilution plate method, the most probable number (MPN) method and Biolog system
were adopted to determine effects of EG03 on characteristics of microbial
community in pepper rhizosphere. It's shown that EGO3's effects on microbial
community in pepper rhizospheric soil varied with time. There were an increase in
the number of fungus and Bacillus spp. to some extent and a significant increase
in that of nitrogen-fixing bacteria. Biolog analysis showed that the curve
between average well color development (AWCD) and incubation time was S-shaped
for all the treatments and that the AWCD of pepper rhizospheric soil at the early
stage was higher than at the late stage. The analysis of carbon source
utilization showed that EG03 decreased microbial utilization of carbon source in
short-term, and the microbial community of pepper rhizospheric soil at the late
stage composed mainly of microbes depended on sugars as carbon resource. EG03
treatment could decrease the five microbial diversity indices of rhizospheric
microbes in short term, then increased those indices instead, especially with
significant (P < 0.05) increases in Simpson index and McIntosh evenness.
PMID- 25129951
TI - [Effects of inoculating plant growth-promoting rhizobacteria on the biological
characteristics of walnut (Juglans regia) rhizosphere soil under drought
condition].
AB - Effects of four plant growth-promoting rhizobacteria (PGPR) , namely Pseudomonas
sp. YT3, Bacillus subtilis DZ1, B. cereus L90 and B. fusiformis L13 on the
biological characteristics of walnut (Juglans regia) rhizosphere soil under
drought stress were investigated. Results showed that drought stress had little
effect on available nutrients of walnut rhizosphere soil, but significantly
decreased the activity of organic carbon by 18.4% and increased the pH from 7.34
to 7.79. Under drought stress condition, the inoculation of Bacillus cereus L90
significantly increased high-labile organic carbon in walnut rhizosphere by 14.5%
relative to the un-inoculated control, and decreased the pH to 7.41. Compared
with the irrigated control, the total microbial populations, root exudates,
microbial biomass carbon, and microbial biomass nitrogen in walnut rhizosphere
soil were significantly decreased by 36.0%, 20.7%, 33.5% and 30.7%, respectively,
because of drought stress. However, L90 inoculation decreased these deficits to
14.1%, 10.3%, 12.1% and 12.7%, respectively. Some terminal restriction fragments
(T-RFs) disappeared under the drought condition and PGPR inoculation had great
influence on T-RFs according to Terminal Restriction Fragment Length Polymorphism
profiles. The Margalef index and the Shannon index of walnut rhizosphere soil
significantly decreased, but the Simpson index increased relative to the
irrigated control. Compared with the un-inoculated control, the Margalef index
significantly increased from 0.42 to 0.99, as well as the Shannon index increased
from 0.52 to 0.98. However, the Simpson index de- creased from 0.60 to 0.39.
Inoculating YT3, DZ1 and L13 had weaker effects on the biological characteristics
of walnut rhizosphere soil compared to inoculating L90, suggesting L90
inoculation could interfere with the suppression of drought stress to the
biological characteristics of walnut rhizosphere soil.
PMID- 25129952
TI - [Nest habitat quality evaluation for the oriental great reed warbler
(Acrocephalus orientalis) in Baiyangdian Wetland].
AB - The Baiyangdian Wetland Natural Reserve is an important breeding habitat for
oriental great reed warbler (OGRWs), Acrocephalus orientalis, in North China
Plain. We investigated the nesting sites of OGRWs by line transect method during
June-July, 2011, and 112 nests were found out in total. The ecological-niche
factor analysis (ENFA) was applied in nesting habitat suitability assessment for
OGRWs in Baiyangdian. The results showed that OGRWs in this reserve preferred
nesting in dry land reed landscapes, which located at relatively high altitudes
and away from anthropocentric disturbance. In 2011, the suitable and the most
suitable nesting habitats of OGRWs in this reserve were 2474.69 hm2 and 1131.19
hm2, accounting 7.6% and 3.5% of the total reserve area, respectively. The most
suitable nesting habitats shaped a circle-like structure, and they all clustered
together around Damai and Shaoche core area, which located in the east part of
the reserve. In order to protect the nesting habitats for OGRWs within
Baiyangdian wetland reserve, it was suggested that the functional zone should be
reorganized, and that the Damai and Shaoche core area should be integrated into
one. This new core area would be bigger and more concentrated, at the same time
the buffer zone should also be established appropriately, so as to protect the
natural landscapes in this reserve as much as possible.
PMID- 25129953
TI - [Photosynthetic activity of Gloiopeltis furcata (intertidal red macroalga) in
response to desiccation].
AB - In this study, the diurnal change of photosynthesis activity in response to
various tidal patterns, the relationship between photosynthetic activity and
tissue water content, and the interactive effect of desiccation and irradiance on
photosynthetic activity in Gloiopeltis furcata were investigated by using
portable pulse amplitude modulated (PAM) fluorometer. Results showed that Fv/Fm
decreased more rapidly during the noon low tide than during the morning- or
evening low tide. F/Fm decreased slowly at the beginning of desiccation during
the morning low tide, but decreased rapidly throughout the evening low tide.
Fv/Fm recovered to the initial values on the same day no matter when the low tide
occurred, suggesting the occurrence of dynamic photoinhibition. These features
endowed G. furcata with an ability to adapt to the periodic desiccation on high
intertidal rocks. The maximum (Fv/Fm) and effective (Phi(PSII)) quantum yield
declined with the decrease of tissue water content (TWC). However, photosynthetic
activity could recover completely when TWC exceeded 6%, showing a strong ability
of G. furcata to tolerate desiccation. The relationships between TWC and Fv/Fm
and Phi (PS II) as were as follows: F/Fm = 0.68 + (0.44-0.68)/[1 +(TWC/ 66.96)]5
, R2 = 0.99; Phi(PSII) = 0.585 + (0.004-0.585)/[1+(TWC/73)10], R2 = 0.99. ANOVA
result further showed that the interactive effect of irradiance and desiccation
on photosynthetic activity was significant, and that the photoinhibition degree
increased with elevation of irradiation and duration of desiccation. The extreme
condition (6 h desiccation at 1000 micromol photons x m(-2) x s(-1)) resulted in
a serious photoinhibition, with the longest period of complete recovery for
photosynthesis activity.
PMID- 25129954
TI - [Seasonal variation of functional diversity of aquatic microbial community in
Apostichopus japonicus cultural pond].
AB - The functional diversity of aquatic microbial communities in sea cucumber
(Apostichopus japonicus) cultural ponds was examined in this paper. The Biolog
plate technique and redundancy analysis (RDA) method were used to evaluate
seasonal changes and their relationships with environmental factors. The results
showed that both total amount and types of carbon sources utilized by microbes in
the sea cucumber cultural ponds varied seasonally, and were the highest in summer
and lowest in winter, with polymers being the main type of carbon sources.
Principal component analysis revealed that the carbon utilization diversity of
the microbial communities varied significantly over the seasonal courses. A total
of 10 categories of carbon sources were significantly related to the principal
component 1, among which were polymers, carbohydrates, carboxylic acids, amino
acids, and amines. Significant seasonal changes were detected for all carbon
utilization diversity indices of the microbial communities, including Shannon,
McIntosh, Simpson, and S-E. However, seasonal variations were different among the
microbial diversity indices. RDA analysis revealed that TP, NO(3-)-N, TN, and
PO4(3-)-P were the critical environmental factors influencing the seasonal
changes in functional diversity of aquatic microbial community in sea cucumber
cultural ponds.
PMID- 25129955
TI - [Estimation of biological parameters and yield per recruitment for Coilia
nasustaihuensis in Dianshan Lake, Shanghai, China].
AB - Coilia nasustaihuensis is the most abundant species in Dianshan Lake and plays an
important role in the lake ecosystem. From July 2010 to August 2011, a total of
3107 samples of C. nasustaihuensis were collected from Dianshan Lake. Based on
length data of these samples, ELEFAN I technique was employed to estimate growth
and mortality parameters, and the Beverton-Holt dynamic model was used to
evaluate the population dynamics trend for C. nasustaihuensis. Growth of this
species was described using avon Bertalanffy model, and the estimated parameters
were Linfinity = 35.70 cm, k = 0.54, and t0 = -0.48 a. The turning point for body
mass growth curve of the stock was situated at t = 1.37 a. Natural mortality
coefficient M was then estimated using Pauly's empirical equation and found to be
0. 872. Length-converted catch curves were used to estimate the total mortality
coefficient Z, which was found to be 2.121. Accordingly, the fishing mortality
coefficient (F) was equal to 1.249, and the current exploitation rate was 0. 589,
suggesting the stock was over-exploited. According to the Beverton-Holt dynamic
model, the minimum capture size for C. nasustaihuensis should be 21.42 cm (age
1.22 years).
PMID- 25129956
TI - [Effects of different host plants on the cold-resistant substances in
overwintering larvae of Carposina sasakii Matsumura (Lepidoptera: Carposinidae)].
AB - To evaluate the influence of different host plants including apple, wild jujube,
jujube, pear and hawthorn on the cold-tolerance substances in overwintering
larvae of the peach fruit moth Carposina sasakii Matsumura, we measured the
larvae super-cooling capacity, the water content (W), total fat content (TFC),
total protein content (TPC) and total glycogen content (TGC) in the body. Results
showed that the mean super-cooling point (SCPs) and freezing point (FPs) of
overwintering larvae from the 5 host plant fruits differed significantly, ranging
from -15.53 to -8.50 degrees C and -11.31 to -4.04 degrees C, respectively. The
overwintering larvae fed on hawthorn owned the highest SCP, FP, TGC and the
lowest W, while those fed on apple had the lowest SCP, FP, TFC and TGC but the
highest W and TPC. The fresh mass (FM) of the overwintering larvae fed on pear
was the highest, while those fed on jujube was very low. Those fed on jujube
accumulated the highest TFC but the lowest TPC.
PMID- 25129957
TI - [Accuracy of predicting in vitro ruminal methane production in goats using
volatile fatty acids stoichiometric models].
AB - This study was conducted to investigate the accuracy of predicting in vitro
ruminal methane (CH4) production using volatile fatty acids (VFA) stoichiometric
models [CH4 = 0.5Ace-0.25Pro + 0.5But-0.25Val] (model 1), where CH4, Ace, Pro,
But and Val are the production amounts of CH4, acetate, propionate, butyrate and
valerate, respectively. Ten common feedstuffs, including four concentrates and
six roughages with a wide range of chemical composition were incubated in serum
bottles, and VFAs and CH4 production at 72 h were determined. The differences
between the predicted and measured CH4 production were quantified using the model
accuracy analysis. The results showed that the predicted CH4 production amounts
were generally greater than the measured values obtained using the model 1, and
the bias, slope and random error were 62.6%, 11.7% and 25.7%, respectively,
indicating that fixed error exceeded 70%. By assuming 80% of total hydrogen being
used for CH4 synthesis, the VFA stoichiometric model could be re-expressed as
[CH4 = 0.8 (0.5Ace-0.25Pro + 0.5But-0.25Val)] (model 2). The root mean square
prediction error (rMSPE = 0.18) for model 2 was less than for model 1 (rMSPE =
0.60). In addition, the bias, slope and random error of the model 2 were 2.1%,
5.7%, 92.3%, respectively, indicating that fixed error was less than 10%. In
model 1, hydrogen formation resulting from VFA production were assumed to be
totally consumed by methanogens for CH4 synthesis, without considering other
pathways of hydrogen metabolism, which was the main factor resulting in the
higher predicted values than the measured values.
PMID- 25129958
TI - [Effects of plant viruses on vector and non-vector herbivorous arthropods and
their natural enemies: a mini review].
AB - Plant viruses transmitted by arthropods, as an important biotic factor, may not
only directly affect the yield and quality of host plants, and development,
physiological characteristics and ecological performances of their vector
arthropods, but also directly or indirectly affect the non-vector herbivorous
arthropods and their natural enemies in the same ecosystem, thereby causing
influences to the whole agro-ecosystem. This paper reviewed the progress on the
effects of plant viruses on herbivorous arthropods, including vector and non
vector, and their natural enemies, and on their ecological mechanisms to provide
a reference for optimizing the management of vector and non-vector arthropod
populations and sustainable control of plant viruses in agro-ecosystem.
PMID- 25129959
TI - [Effects of iron on the algae growth and microcystin synthesis: a review].
AB - Iron, as one of the essential mineral elements for algae growth, plays an
extremely important role in the physiological processes such as plant
photosynthesis, respiration, nitrogen fixation, protein and nucleic acid
synthesis. In view of the fact that iron in different forms could be absorbed and
utilized by algae, the existing forms and circulation approaches in the aquatic
environment, the absorption mechanism by algae, and the effects on algae growth
and microcystin synthesis were reviewed in this paper. The relevant microcystin
synthesis genes and their expression under iron restricted conditions were
summarized, and the research directions for harmful algal blooms regulation and
control by ferritin genes were suggested. It was hoped to provide the reference
for eutrophication remediation technology.
PMID- 25129960
TI - [Applications of stable isotope analysis in the trophic ecology studies of
cephalopods].
AB - Cephalopods play an important role in marine food webs, however, knowledge about
their complex life history, especially their feeding ecology, remains limited.
With the rapidly increasing use of stable isotope analysis (SIA) in ecology, it
becomes a powerful tool and complement of traditional methods for investigating
the trophic ecology and migration patterns of invertebrates. Here, after
summarizing the current methods for trophic ecology investigation of cephalopods,
applications of SIA in studying the trophic ecology of cephalopods were reviewed,
including the key issues such as standardization of available tissues for SIA
analyzing, diet shift and migration patterns of cephalopods, with the aim of
advancing its application in the biology of cephalopods in the future.
PMID- 25129961
TI - [Control study on risk factors of children with secretory otitis media nested
case].
PMID- 25129962
TI - [Mutation screening in taperin gene in Chinese with prelingual nonsyndromic
hearing impairment].
AB - OBJECTIVE: To screen and identify the frequency and characteristic of mutation in
stereocilium-related gene Taperin of Chinese prelingual nonsyndromic hearing
impairment with DNA microarray combined with PCR. METHOD: One hundred and thirty
four patients of prelingual nonsyndromic deafness and one hundred health
individuals in China were investigated in this study. Genomic DNA was extracted
from the patients and was subjected to DNA microarray to screen mutations in 4
most common genes. The samples that carried none of the common mutant alleles
were subjected to PCR and sequenced to detect mutations in Taperin gene. RESULT:
Ninteen out of one hundred and thirty-four patients of prelingual nonsyndromic
deafness were detected carring common deafness gene with DNA microarray. Taperin
gene were detected in one hundred and fifteen patients with PCR. A187S was
detected in Taperin as hetrozygous state in 2 patients and their unaffected
members of their family. It occurred at the evolutionary conservation of the
amino acids of taperin according to alignment analysis. Two polymorphism, 157C>T
and 318C>T, were found in the patients and the control group. CONCLUSION: A novel
Taperin mutation, A187S was detected in Chinese patients with prelingual
nonsyndromic hearing loss, which may be relevant to hearing loss. Two
polymorphism, 157C>T and 318C>T, were found in Chinese in our research. The
carrier frequency for Taperin mutation is about 1.74% of prelingual nonsyndromic
deafness in Chinese patients.
PMID- 25129963
TI - [Analysis on GJB2 gene mutations with nonsyndromic hearing impairment in Kazak
patients of Xinjiang].
AB - OBJECTIVE: To study mutations in the GJB2 gene in Kazak patients with
nonsyndromic hearing impairment from Xinjiang. METHOD: One hundred and ninety
three cases of Kazak from the Xinjiang region, including 97 cases of hearing loss
and 96 cases of normal people, were performed mutational analysis of the GJB2
coding region by PCR-direct sequencing. RESULT: Eight kinds of mutation were
found in the encoding region of hearing impairment group:12 cases of 35 delG
homozygous, 5 cases of 79G>A homozygous, 8 cases of 79G>A heterozygous, 1 case of
79G>A heterozygous and 608T>C heterozygous, 5 cases of 79G>A heterozygous and
341A>G heterozygous, 4 cases of 235 delC heterozygous, 2 cases of 341A>G
heterozygous, 1 case of 439T>G heterozygous, 1 cases of 457G> A heterozygous, 2
cases of 521G>A homozygous. Four kinds of mutations found in the normal group
were confirmed as common polymorphic mutation. CONCLUSION: The study suggests
that the GJB2 gene mutation of the Kazak deaf population in Xinjiang has ethnic
and regional characteristics. There is a rather high carrier frequency of GJB2
mutation of Kazak patients in Xinjiang. In this study the 35 delG mutation is a
common mutation of Kazak patients.
PMID- 25129965
TI - [Clinic significance of CT scan in diagnosis and management unsudden unilateral
sensorineural hearing loss].
AB - OBJECTIVE: To investigate the clinic significance of the temporal bone high
resolution CT in discovering unilateral sensorineural hearing loss of
adolescents, and to provide the basis for the rational using of medical
resources. METHOD: A retrospective study was conducted on 28 outpatients with
unilateral sensorineural hearing loss at unsure time. Their medical history and
CT examine were reevaluated,combined with associated articles in this report.
RESULT: All of the 28 patients with unilateral sensorineural hearing loss had the
normal external ear and middle ear and received CT scan. Nine out of twenty-eight
cases had inner ear malformation. Among the nine cases, 1 cases was Mondini
malformation and 1 cases was common cavity, 5 cases were single stenosis of IAC,
and 2 cases were semicircular canal and vestibular malformation. 19 cases were
not found abnormal by CT, and 4 cases had had suffered from mumps. CONCLUSION: CT
scan was available in diagnosis of unsudden unilateral sensorineural hearing
loss, which would help us to use medical resource more rationally.
PMID- 25129964
TI - [DNA microarray screening analysis in children with profound hearing impairment
in Hubei province].
AB - OBJECTIVE: To investigate characteristics of molecular etiology of children with
profound sensorineural hearing loss in Hubei province, and to provide reference
for deafness treatment and genetic counseling. METHOD: Three hundred and six
children with profound sensorineural hearing loss in Hubei province were
enrolled, their genomic DNA were extracted from peripheral blood and a deafness
gene test chip was used to screen nine hot spot mutation in the GJB2, GJB3,
SLC26A4, and mitochondria 12SrRNA gene. All patients with SLC26A4 gene mutation
were given temporal bone CT scan. RESULT: One hundred and thirty-two (43.14%) out
of 306 children were found carrying at least one pathogenic gene mutation. The
mutation rates of GJB2, SLC26A4 and mitochondria DNA 12SrRNA gene were 29.41%
(90/306), 13.72% (42/306) and 0.65% (2/306), respectively. None out of 306
children was detected GJB3 gene mutation. Thirty-six patients carrying SLC26A4
gene mutation were detected enlarged vestibular aqueduct by CT scan. CONCLUSION:
Mutations of GJB2 and SLC26A4 gene are two major pathogenic gene for genetic
hearing loss in children. 235delC mutation is the main mutation type, followed by
IVS7-2A> G mutation type. The screening of SLC26A4 gene common mutations
contribute to the diagnosis of enlarged vestibular aqueduct syndrome.
PMID- 25129966
TI - [Cochlear implantation in patients with cochlear ossification].
AB - OBJECTIVE: To investigate cochlear implantation surgical techniques and
postoperative results in patients with cochlear ossification. METHOD: Twenty-nine
cochlear ossification patients with cochlear implantation in our department were
retrospectively studied during 1997-2011. Preoperative imaging and
electrophysiological assessment were done to classify the cochlear ossification
of all the patients. Categories of auditory performance and speech
intelligibility rating were detected to assess the outcome of cochlear implant
postoperatively. RESULT: Among 29 cases with cochlear ossification, 19 cases were
grade II, 4 cases were grade I, 4 cases were grade III, and 2 cases were apical
turn ossification. Among 23 patients with cochlear ossification grade I and II,
17 cases were totally cochlear array insertion, and 6 cases were partial cochlear
array insertion. Patients with cochlear ossification grade III were all partial
cochlear array insertion. Most patients achieved good hearing and language
ability after cochlear implantation. CONCLUSION: Cochlear implantation can be
successfully performed on the basis of systematic preoperative assessment and
some patients can achieve good postoperative results in patients with cochlear
ossification. Intraoperative electrical stimulation of the auditory evoked
response provides a good method to assess the residual spiral nerve function.
PMID- 25129967
TI - [Complementary self-treatment for posterior canal benign paroxysmal positional
vertigo].
AB - OBJECTIVE: To examine the value of self-treatment for Posterior canal benign
paroxysmal positional vertigo (PC-BPPV). The treatment effect was compared
between patients treated with modified Epley in outpatient clinic combined with
self treatment at home and patients treated by modified Epley alone. METHOD: A
randomized controlled trial were carried out in the Department of Otolaryngology
Head and Neck Surgery, the Affiliated Sixth People's Hospital of Shanghai Jiao
Tong University from December 2012 to May 2013. 147 out of 150 patients with
unilateral idiopathic BPPV-PSC were enrolled in follow-up. Among which, 73
patients were allocated in modified Epley-alone group and 74 were allocated in
slef-treatment group. RESULT: The success rate was 53.4% in modified Epley-alone
group vs 83.8% in self-treatment group (P < 0.01) after 1 week treatment. In the
modified Epley-alone group,the success rate of hand repositioning group and chair
assisted repositioning group was 45.9% vs 61.1% (P > 0.05), the risk rate was
0.752, 95% CI (0.486 - 1.163). In the self-treatment group, the success rate of
hand repositioning group and chair-assisted repositioning group was 87.5% vs
81.0% (P > 0.05), the risk rate was 1.081, 95% CI (0.888-1.316). Incidence rate
of serious complications was 0% in the modified Epley-alone group and 1.3% in the
self-treatment group (P > 0.05). CONCLUSION: Complementary self-treatment with
modified Epley maneuver treated PC-BPPV sooner and more effectively, Compared
with modified Epley maneuver alone. And its incidence rate of serious
complications didn't increase. Chair-assisted repositioning showed better result
than hand repositioning alone, and self-treatment at home can reduce the effect
of the gap. We found that complementary self-treatment with modified Epley
maneuver had more benefits for patients with PC-BPPV.
PMID- 25129968
TI - [Research of cochlear coiling pattern and orientation in general population by CT
3D reconstruction].
AB - OBJECTIVE: To perform morphometric analysis of bilateral cochleae in all subjects
based on computed 3-dimensional reconstruction tomographic data and assist the
surgeon in diagnosing the inner ear abnormality or surgical strategies. METHOD:
Two hundred normal developed cochleae from 100 patients were divided into 5
groups according to age. Morphometric analysis of bilateral cochleae was
performed in all subjects by 3D reconstructions and 2D multiplanar reformation.
The length and width of the cochlear base, the length within the cochlear base,
the height of the cochlea, the angle between the first and second turn of the
cochlea, and the cochlear orientation within the cranial base were measured and
compared in different age, sex and bilateral groups. RESULT: The length of the
cochlear base was (8.56 +/- 0.52)mm, the width was (6.63 +/- 0.56)mm, the length
within the cochlear base was (7.33 +/- 10.56)mm, the height of the cochlea was
(3.76 +/- 0.28)mm, and the angle between the first and second turn of the cochlea
was (15.82 +/- 2.78)degrees. All index above did not change significantly in
different aging, sex or side (P > 0. 05). Variability in the angle between the
first and second turn of the cochlea was considerable, and a smaller angle (from
the midsagittal line) was showed in the older age groups than the younger groups
(P < 0.05). CONCLUSION: 3D and 2D volume rendering enables us to evaluate the
features of cochlear morphology and orientation that may assist the surgeon in
diagnosing the inner ear abnormality or surgical strategies.
PMID- 25129969
TI - [A comparison of 226 Hz and 1 000 Hz tympanometry in diagnosis of infants otitis
media effusion].
AB - OBJECTIVE: To provide a clinical reference by comparing the conventional 226 Hz
tympanometry with 1000 Hz tympanometry in two groups of young children with
otitis media effusion evidenced by CT scan. METHOD: One hundred and seventy-seven
young children (226 ears), from 1 to 60 months, with otitis media effusion were
involved in this study. They were divided into six groups by age: 0-6 months
group, 6-12 months group, 12-18 months group, 18-24 months group, 24-36 months
group, 36-60 months group. They were tested with tympanometry of 2 probe-tones of
226 and 1 000 Hz. Type A tympanogram was defined as a normal middle ear function
in 226 Hz and single-or double-peak in 1 000 Hz tympanometry. One hundred and
fifty-eight normal young children (266 ears) were selected as control group. The
results were analysed with Chi square test. Receiver operator characteristic
(ROC) analysis was performed to evaluate the two methods. RESULT: In the young
children with otitis media effusion, the detection rate of 226 Hz tympanogram in
six groups was 21.1%, 35.2%, 46.9%, 42%, 62.5% and 68% respectively, while 94.7%,
98.1%, 96.9%, 91.2%, 95.8% and 88% respectively in 1 000 Hz tympanogram. In the
young children with normal middle ear function, the detection rate of 226 Hz
tympanogram in six groups was 95.1%, 88.6%, 85.1%, 93.3%, 88.5% and 93.5%, while
87.8%, 94.3%, 89.4%, 95.6%, 94.2% and 97.8% respectively in 1 000 Hz tympanogram.
The detection rate was significantly different between 226 and 1 000 Hz
tympanogram in the young children under 36-month old. CONCLUSION: A single-or
double-peak 1000 Hz tympanometric patterns as normal criteria was a simple way to
evaluate young children s' middle ear function. 1 000 Hz tympanometry should be
given priority to the children within 36-month old in detection middle ear
function,the 226 and 1 000 Hz tympanometry should be done at the same time within
36-60 months old.
PMID- 25129970
TI - [Analysis of TEOAE and AABR hearing screening and follow-up in NICU].
AB - OBJECTIVE: To study the results of TEOAE and AABR hearing screening and follow-up
in NICU. METHOD: Total 574 cases in NICU were included in this study, all cases
received both TEOAE and AABR hearing screening while admission and rescreening
when one-month-old. The cases that were abnormal on either test in rescreening
were asked to return for diagnostic tests at 3 moths old. The patients who didn't
return as required in 3 months were surveyed by call and analyzed. RESULT: Among
574 cases, 472 cases passed both TEOAE and AABR hearing screening while
admission. While 102 cases had abnormal test results in either screening test.
Thirty-three cases returned for follow-up, 13 of which passed rescreening test
one month after discharge, the other 20 cases had ABR diagnostic tests after 3
months. Among them, 8 cases had normal hearing, 12 cases had various degree of
hearing loss. Sixty-nine cases lost follow-up. The reason of lost follow-up was
as follows, parents changed phone number/contact information, parents didn't
understand the screening results, parents believe that their children having no
need for further testing; parents had retest in other hospitals, parents didn't
pay attention to hearing loss because of other severe complicated comorbidities.
CONCLUSION: The passing rate (normal) of TEOAE and AABR hearing screening in NICU
was 82.2%, non- passing rate wass 17.8%, and the prevalence of hearing loss was
high in those followed cases. Hyperbilirubinemia was the main risk factors of
hearing loss in our NICU patients. We reviewed the reason for high rate (67.6%)
of losing follow-up.
PMID- 25129971
TI - [Effect of ossicular chain reconstruction with titanium ossicular replacement
prosthesis in mastoidectomy with synchronous ossiculoplasty].
AB - OBJECTIVE: To assess hearing effect of ossicular chain reconstruction with
titanium ossicular replacement prosthesis during mastoidectomy with synchronous
ossiculoplasty in chronic middle ear disease. METHOD: Retrospective reviews were
performed for 139 patients who had underwent mastoidectomy and tympanoplasty with
titanium ossicular replacement prostheses at the same time between 2008 and 2011.
The partial ossicular replacement prostheses (PORP) were used in 91 patients and
the total ossicular replacement prostheses (TORP) were used in 48 patients
respectively. All patients had follow-up for 2 to 5 years. The preoperative and
postoperative mean air conduction and air-bone gaps(ABG) for the four frequencies
(0.5, 1.0, 2.0 and 4.0 kHz) were evaluated. The improvement of mean air
conduction and ABG over the same frequencies were measured. A postoperative ABG
less than or equal to 20 dB was considered a successful operation. The hearing
results of titanium PORP and TORP were compared. RESULT: The mean air conductions
were (53.97 +/- 11.32)dB and (36.80 +/- 11.68) dB preoperatively and
postoperatively in PORP group. The mean improvement in air conduction was (17.17
+/- 5.79)dB. The mean ABG was (31.84 +/- 6.17)dB and (15.13 +/- 7.22)dB
preoperatively and postoperatively in PORP group. The mean improvement in ABG was
(17.71 +/- 5.5)dB. The difference of hearing threshold between preoperative and
postoperative had statistical significance (P < 0.01). The mean air conduction
were (58.05 +/- 11.35)dB and (44.53 +/- 13.15)dB preoperatively and
postoperatively in TORP group. The mean improvement in air conduction was (13.52
+/- 7.81)dB. The mean ABG; were (35.67 +/- 5.73)dB and (21.48 +/- 7.01)dB
preoperatively and postoperatively for TORP group. The mean improvement of
hearing threshold in ABG was (14.18 +/- 7.53)dB. The difference of hearing
threshold between preoperative and postoperative had statistical significance (P
< 0.01). ABG less than 20 dB after operationwas happened in 68.63% of the
patients (74.73% for PORP and 54.17% for TORP). There was statistically
significant difference between PORP and TORP (P < 0.05). CONCLUSION: We conclude
that titanium ossicular reconstruction during mastoidectomy with synchronous
ossiculoplasty give stable and excellent hearing results. We obtained better
results with PORP than with TORP.
PMID- 25129972
TI - [Paraglottic space primary paraganglioma: a case report and review].
AB - OBJECTIVE: To investigate the clinical feature, diagnose and therapeutic methods
of paraglottic space primary paraganglioma. METHOD: One case of paraglottic space
primary paraganglioma was reported and the relevant literatures were reviewed.
RESULT: One case showed a hoarse voice, who was cured after the surgery of neck
incision. NSE and CgA were positively expressed. CONCLUSION: Paraganglioma of the
paraglottic space is very rare. The diagnosis of paraglottic space primary
paraganglioma bases on histopathology and immunohistochemistry. The
immunohistochemistry and clinical character must be comprehensively analyzed to
increase the diagnosis accuracy.
PMID- 25129973
TI - [Comparison of application of several psychophysical olfactory test methods in
clinic].
AB - OBJECTIVE: To compare the consistency of four olfactory psychophysical test
methods. METHOD: Twenty out-patients were done with olfactory psychophysical test
and the results were analyzed. The four olfactory psychophysical test methods
include simple test method, UPSIT, Sniffin Sticks test and the T&T olfactometer
test. RESULT: The consistency of four test methods reached 85%, and UPSIT test
can identify pseudo smell obstacles. CONCLUSION: There is reliable and stable
outcome of the four psychophysical olfactory test methods.
PMID- 25129974
TI - [Investigation of skin prick test on patients with allergic rhinitis in Urumqi
area].
AB - OBJECTIVE: To investigate the geographic distribution of air-borne allergens
which caused allergic rhinitis in Urumqi, and offer guide for prevention and
treatment of the patients with allergic rhinitis. METHOD: Skin prick tests were
performed on 350 patients with allergic rhinitis by assay of Novo-helisen depot
(NHD) fluid. RESULT: The total positive rate of inhaled allergens among 350
patients was 78.86%. The most frequent of allergen was chenopodium 78.86% (255
cases). The other frequent allergens were ragweed 36.86% (128 cases), artemisir
28% (98 cases), timothy 27.14% (95 cases), elm 5.71% (90 cases), willow 25.14%
(88 cases), poplar 18.86% (66 cases), cockroach 18.86% (66 cases), dust-mite
14.86% (62 cases), flour mite 14.86% (52 cases), alternaria spp 2.86% (10 cases).
Allergen were multiple in most AR patients. There was not statistically
significant difference between the sexes. There was statistically significant
difference between the tribes. CONCLUSION: Chenopodium, ragweed and artemisir
were the main allergens in patients with allergic rhinitis in Urumqi.
PMID- 25129975
TI - [Effect of ambroxol on biofilm of Haemophilus influenzae and bactericidal
action].
AB - OBJECTIVE: To establish a biofilm model of Haemophilus influenzae and observe the
effect of ambroxol on biofilm of Haemophilus influenzae and bactericidal action.
METHOD: Thirty strains of Haemophilus influenzae were isolated from adenoids of
children with adenoidal hypertrophy. Two strains which could build stronger
biofilms was selected in a 96-well plate. The effect of ambroxol on biofilms were
determined by crystal violet, and the structure of biofilms were observed by
scanning electron microscope (SEM). The numbers of viable bacterial in biofilm
after ambroxol treatmented determined by plate culture count. RESULT: Through
crystal violet assay, significant difference (P < 0.01) between the two group
after treatment was found when ambroxol concentration reached at 0.25 mg/ml and
0.49 mg/ml. The biofilms was destroyed by SEM. Ambroxol had the positive effect
on bacterial killing by plate culture count,and the effect was in a dose
dependent. CONCLUSION: Ambroxol could destroy the biofilm of Haemophilus
influenzae, and had bactericidal function in vitro.
PMID- 25129976
TI - [Multiple factors quantitative analysis on middle ear function in primarily
diagnosed patients with nasopharyngeal carcinoma].
AB - OBJECTIVE: To explore the ways of quantitative and objective evaluation for
analyzing the multiple influence factors on middle ear function in the patients
with primarily diagnosed NPC, and to analyze the influence factors of middle ear
function in the patients with primarily diagnosed nasopharyngeal carcinoma (NPC).
METHOD: Three hundred and twenty cases (320 ears) of primarily diagnosed NPC
patients were examinated with electric otoscope, acoustic immittance measurement,
pure tone audiometry, nasopharynx and middle ear CT or MRI scanning, eustachian
tube function examination, and electronic nasopharyngoscope. A series of
quantitative methods, as the influence factors including T stage, clinical stage,
location, diffusion type and form of tumor, eustachian tube function, pharynx
mouth shape, imaging extension (nasal, skull base, pharyngeal recess,
parapharyngeal space, tensor veli palatini muscle, levator veli palatini and so
on), were used to evaluate the middle ear function. SPSS 13.0 was used to anlyze
the single and multiple factors in statistics. RESULT: T stage, clinical stage,
location, diffusion type, and form of tumor, pharynx mouth shape, imaging
extension (nasal, skull base, pharyngeal recess, parapharyngeal space, tensor
veli palatini muscle, levator veli palatini) were the single influence factors on
the function of middle ear in primarily diagnosed NPC patients. The gender, age,
pathological types, N staging and M staging of NPC patients primarily diagnosed
had no effect on middle ear function. The multple factors analysis showed that T
stage, tumor location, the function of eustachian tube, tensor veli palatini
muscle invasion, and skull base invasion were independent factor of affecting the
middle ear function on primarily diagnosed NPC patients. CONCLUSION: In this
study, the influence factors of middle ear function with primarily diagnosed NPC
were related to T stage, location of tumor, the function of eustachian tube,
tensor veli palatini muscle invasion, skull base invasion, otitis media and
quantitative criteria. The way of quantitative analysis could be used to evaluate
objectively the middle ear function in patients with primarily diagnosed NPC.
PMID- 25129977
TI - [Silenced NgR gene expression by RNA interference to promote rats facial nerve
regeneration in vitro].
AB - OBJECTIVE: To suppress NgR gene expression in neural stem cells and observe
differentiation of neural stem cells in vitro after interfered which provide
nutritional support for the facial nerve repair in vivo. METHOD: PCR
amplification, restriction endonuclease digestion, T4DNA ligase connections were
used to connected NgR with rector pGCsi, and constructed recombinant vector (NgR
shRNA). Lipofectamine 2000 were used to transfect the NSC. The expression of NgR
was examined by Western Blot. The proportion of neural stem cells transformed
into neurons after transfection was tested by Immunocytochemistry. Neural stem
cells were planted in PLGA tubes after transfected, and were scanned by electron
microscopy. RESULT: NgR shRNA plasmid was constructed and infected neural stem
cells successfully. Western Blot showed that the expression of NgR decreased in
neural stem cells after interference. Immunocytochemistry showed that the rate of
the neural stem cells transformed into neurons after interfered was significantly
higher (P < 0.01). CONCLUSION: Neural stem cells were transformed into neurons
after NgR shRNA plasmid infected neural stem cells, which promoted axonal
regeneration more effectively and provided a efficient and stable gene platform
for facial nerve repair.
PMID- 25129978
TI - [The effect of forsythiaside on the expression of c-jun induced by cisplatin in
the cochlea of guinea pig].
AB - OBJECTIVE: To study the effect of forsythiaside on the expression of c-jun
induced by cisplatin in the cochlea of guinea pig. METHOD: Thirty guinea pigs
were randomly divided into control group (10), cisplatin group (10) and
forsythiaside group (10). The ototoxicity model was done with intraperitoneal
injection of cisplatin solution (8 mg/kg per day) for 7 days. Forsythiaside (25
mg/kg per day) was injected 30 min before cisplatin solution treated in guinea
pigs of forsythiaside group for 7 consecutive days. The saline instead of
cisplatin was injected in normal control group. The distortion product
otoacoustic emission (DPOAE) was detected before animals were killed. The
expression of c-jun in cochlea of guinea pigs was detected by western blotting.
The expression of c-jun mRNA in cochlea of guinea pigs was detected by reverse
transcriptase polymerase chain reaction (RT-PCR). RESULT: DPOAE amplitudes in
cisplatin group was significantly lower than in control group (P < 0.01).
Compared with cisplatin group, DPOAE amplitudes in forsythiaside group was
increased significantly (P < 0.05). The expression of c-jun protein and mRNA were
significantly increased in cisplatin group than in control group (P < 0.01).
Compared with cisplatin group, the expression of c-jun protein and mRNA were
significantly decreased in forsythiaside group. CONCLUSION: Forsythiaside can
significantly reduce the side effects induced by cisplatin through down
regulating the expression of c-jun.
PMID- 25129979
TI - [Clinical efficacy of mouse nerve growth factor in the treatment of sudden
deafness].
AB - OBJECTIVE: To study the clinical efficacy of mouse nerve growth factor (NGF) in
the treatment of sudden deafness. METHOD: A retrospective analysis was performed
on 115 cases of hospitalized patients who were suffered from sudden deafness.
Patients were divided into two groups according to treatment medicine. Control
group: patients were treated with intravenous vasodilators, energy mixture,
steroid pulse therapy, and methylcobalamin neurotrophic therapy. NGF group:
intramuscular NGF treatment was added on the basis of conventional therapy
mentioned above. Both treatments lasted 14 days, the total efficiency were
compared. Patients were further divided into sub-groups according to age,
duration and the level of pre-treatment PTA, and the treatment efficiency was
further compared. By SPSS 11.0 statistical analysis, a P < 0.05 was considered as
statistical significant difference. RESULT: (1) The total efficiency of NGF group
was significantly higher than control group. (2) Regard of age, the efficiency of
NGF treatment group was significantly higher than control group. (3) For the
patients whose duration were less than 7 d, or the PTA < or = 60 dBHL, the
efficiency of NGF group were significantly higher. For the patients whose
duration were more than 7 d, or the PTA>60 dBHL, the efficiency of NGF therapy
was not superior to the traditional treatment. CONCLUSION: NGF can significantly
improve the symptom of patients with short duration or low PTA. For this kind of
patients, NGF adjuvant therapy should be recommended. For the patients with
longer duration and higher level of PTA, NGF therapy is not advocated. NGF
treatment should not be in consideration of the age.
PMID- 25129980
TI - [The clinical application of modified rhytidectomy incision in superficial
parotid tumor surgery].
AB - OBJECTIVE: To evaluate the modified rhytidectomy incision in superficial
parotidectomy. METHOD: Thirty-five patients with superficial parotid tumor were
included in this study. A modified rhytidectomy incision often used in facial
plastic surgery was used for superficial parotidectomy and subtotal superficial
parotidectomy with preservation of facial nerve and great auricular nerve. The
follow-up study included the exposed region, the cosmetic effect of this approach
and the rate of complication. RESULT: All patients healed without salivary
fistula, and were satisfied with this modified approach. Temporary paralysis of
the marginal mandibular branch of facial nerve were found in five patients, and
six patients felt insensible around earlobe after operation. They all recovered
in 1 to 3 months after surgery, no recurrence was happened during follow-up in 36
to 60 months (median follow-up period was 48 months). CONCLUSION: The modified
rhytidectomy incision provided good exposure, had less complication and better
cosmetic outcome.
PMID- 25129981
TI - [Microsurgical efficacy of cholesteatoma of external auditory canal combined with
filling drugs by ear endoscopy].
PMID- 25129982
TI - [Perioperative treatments of congenital microtia with auricular reconstruction].
PMID- 25129983
TI - [The position and protection of the vertical facial nerve during cochlear
implantation guided by HRCT].
PMID- 25129984
TI - [The development and application of MRI of the inner ear after gadolinium
injections in the diagnosis of Meniere's disease].
AB - Due to the lack of objective examination method, the diagnosis of Meniere's
disease mainly relies on subjective symptoms. MRI of the inner ear after
gadolinium injections had become a new technology in otology in recent years. The
image can clearly distinguish perilymph from endolymph in the labyrinth and can
be applied to the imaging diagnosis, evaluation of treatment and the pathogenesis
research of Meniere's disease. This article is a review of the development and
the application in clinical research of this new technology.
PMID- 25129985
TI - [The giant mucous cyst of frontoethmomaxillary sinus: one case report].
AB - One case of rare giant mucous cyst of nasal sinus that implicated frontal,
ethmoid and maxillary sinus was in our hospital. The patient manifested mainly
slowly developing swelling and pain of cheek, exophthalmos and visual impairment.
The image studies indicated cyst of nasal sinus, including frontal, ethmoid, and
maxillary sinuses. The clinical diagnosis was cyst of frontoethmomaxillary sinus.
PMID- 25129986
TI - Carboplatin dosing for adult Japanese patients.
AB - Carboplatin is a platinum-based anticancer drug that has been long used to treat
many types of solid cancer. Because the clearance of carboplatin strongly
correlates with the glomerular filtration rate (GFR), its dosage is calculated
with the Calvert formula on the basis of the patient's GFR to achieve the target
area under the plasma drug concentration-time curve (AUC) for each patient.
However, many lines of evidence from previous clinical studies should be
interpreted with caution because different methods were used to estimate drug
clearance and derive the dosage of carboplatin. There is a particularly high risk
of carboplatin overdosing when the dosage is determined on the basis of
standardized serum creatinine values. When deciding the dose of carboplatin for
adult Japanese patients, preferred methods to assess renal function instead of
directly measuring GFR include (1) 24-h urinary collection-based creatinine
clearance adjusted by adding 0.2 mg/dl to the serum creatinine concentration
measured by standardized methods, and (2) equation-based GFR (eGFR) with a back
calculation to units of ml/min per subject. Given the limitations of serum
creatinine-based GFR estimations, the GFR or creatinine clearance should be
directly measured in each patient whenever possible. To ensure patient safety and
facilitate a medical-team approach, the single most appropriate method available
at each institute or medical team should be consistently used to calculate the
dose of carboplatin with the Calvert formula.
PMID- 25129987
TI - Retrospective case series of 15 patients treated with chemoradiation using 5-FU
and nedaplatin for gynecological malignancy: with regard to hemotoxicity.
AB - We conducted a retrospective comparison of the hemotoxicity of the sequential
administration of 5-Fluorouracil (5-FU) prior to Nedaplatin (NDP) (FN therapy)
and that of its reverse sequence (NF therapy) for gynecological malignancy. From
February 2002 to November 2004, a total of 15 gynecological malignancy patients
were treated with radiation therapy combined with NDP and 5-FU. Of these 15
patients, 5 were treated with NF therapy, and 10 were treated with FN therapy. No
significant differences were detected between the FN and NF groups with regard to
white blood cell count (WBC), hemoglobin level (Hb), and platelet count. The
results of this study do not show that the FN group has a lesser degree of
hemotoxicity than the NF group.
PMID- 25129988
TI - Family support for women's health-seeking behavior: a qualitative study in rural
southern Egypt (Upper Egypt).
AB - This qualitative study investigated the influence of family support on women's
health-seeking behavior in rural southern Egypt (Upper Egypt). We carried out
separate focus group discussions (FGDs) with 3 groups (6 women with children
under 5 years old, 6 men, and 4 elderly women, respectively) in a village in
Assiut Governorate, an underprivileged region in Upper Egypt. The FGDs aimed to
identify how different types of family support affected women's health-seeking
behavior in areas including maternal health and common illnesses of women and
children. Our results showed that maternal health issues were often discussed by
husbands and wives, while mothers-in-law had little apparent influence. We also
found that women could access support resources more easily than expected through
their extended families. Our study showed that husbands had an important role in
encouraging women's health in the family, while the effect of mothers-in-law on
women's health-seeking behavior was not substantial. The study indicated that
women received considerable support from co-resident family members, their natal
family, and their neighbors, which helped women in seeking health services.
PMID- 25129989
TI - Useful base plate to support the head during Leksell skull frame placement in
gamma knife perfexion radiosurgery.
AB - We developed an original base plate to support both the patient's head and a
Leksell stereotactic skull frame during frame placement in the supine position.
The base plate is made of transparent acrylic board with holes at the posterior
posts for injection of local anesthetics and maneuver of fixation screws through
them. A stable and comfortable position of the patient's head in a supine
position is obtained and maintained on this base plate with an air-pressure cuff
beneath the patient's head. The patient is able to keep a stable, relaxed and
comfortable posture during the procedures of skull frame placement.
PMID- 25129991
TI - A learning curve in aortic dissection surgery with the use of cumulative sum
analysis.
AB - This study demonstrates the risk adjusted cumulative sum analysis of an
individual surgical learning curve for acute type A aortic dissection surgery.
Thirty consecutive patients were operated by a single surgeon for acute type A
aortic dissection from April 2001 to March 2008. Operative variables, mortality,
and major morbidities were analyzed. The learning curve was calculated by
cumulative sum analysis. The anticipated 30-day operative mortality rate was 20.2
+/- 12.7% (range, 3.3-56.7%) and the expected 30-day mortality and morbidity rate
was 47.0 +/- 13.3% (range, 21.7-70.6%) according to the Japan SCORE calculator.
The observed operative and in-hospital mortality rate was 6.67% (two patients),
and the observed major postoperative morbidity rate was 10.0% (three patients).
Risk-adjusted cumulative sum analysis revealed that no excess deaths occurred
beginning at the seventh case and thereafter. The surgeries for acute type A
aortic dissection could be performed at the professionally permissive level from
the beginning. Risk-adjusted cumulative sum analysis was a useful tool to monitor
the performance of the surgical procedure.
PMID- 25129990
TI - Premature cardiac senescence in DahlS.Z-Lepr(fa)/Lepr(fa) rats as a new animal
model of metabolic syndrome.
AB - Aging is accelerated by metabolic and cardiovascular diseases, and the risk of
these diseases increases with age. Obesity is an important risk factor for many
age-related diseases and is linked to reduced telomere length in white blood
cells. We investigated whether cardiac senescence might be enhanced in DahlS.Z
Lepr(fa)/Lepr(fa) (DS/obese) rats, which we recently established as a new animal
model of metabolic syndrome. The heart of DS/obese rats was compared with that of
homozygous lean littermates (DahlS.Z-Lepr+/Lepr+, or DS/lean, rats). DS/obese
rats manifested hypertension as well as left ventricular hypertrophy, fibrosis,
and diastolic dysfunction at 18 weeks of age. Myocardial oxidative stress and
inflammation were increased in DS/obese rats compared with DS/lean rats. Telomere
length in myocardial cells did not differ between the two rat strains, whereas
telomerase activity and expression of the telomerase reverse transcriptase gene
were increased in DS/obese rats. Expression of the senescence-associated genes
for checkpoint kinase 2 (Chk2), p53, and p21 as well as that of genes related to
the renin-angiotensin-aldosterone system were also up-regulated in the DS/obese
rat heart. Our results indicate that DS/obese rats undergo premature cardiac
senescence as well as cardiac remodeling in association with the development of
diastolic dysfunction in these animals.
PMID- 25129993
TI - A novel method for managing water and electrolyte balance after transsphenoidal
surgery: preliminary study of moderate water intake restriction.
AB - Hyponatremia is a common and potentially serious complication of transsphenoidal
surgery (TSS). Since September 2009, we have implemented moderate water intake
restriction (< 2500 mL/day) after TSS in an attempt to prevent this complication.
The aim of this study was to investigate the efficacy of a combination of
moderate restriction of water intake plus antidiuretic hormone (arginine
vasopressin [AVP]) replacement therapy in patients with diabetes insipidus (DI)
for reducing the incidence of delayed hyponatremia after TSS. Patients treated
from September 2005 to August 2009 were allowed to drink water freely after
surgery (the control group), while patients treated from September 2009 to June
2012 were restricted to less than 2500 mL water per day (the water restriction
group). To reduce the occurrence of hypernatremia, AVP replacement therapy was
provided immediately after the development of DI. We retrospectively analyzed the
incidence of hyponatremia, DI, and hypernatremia in patients following TSS.
Hyponatremia incidence was significantly lower in the water restriction group (P
= 0.017); however, there were no significant differences in DI incidence and
hypernatremia incidence between the 2 groups. Under DI control with AVP
replacement therapy, the water restriction group showed no significant difference
in the daily self-rated thirst level for the patients with and without DI.
Moderate water intake restriction in addition to AVP replacement therapy
significantly decreases the incidence of hyponatremia without patient discomfort
(extreme thirst) and other complications. However, further studies are required
to determine the most effective amount of water and the optimal duration of
postoperative water restriction.
PMID- 25129992
TI - Glucocorticoids activate cardiac mineralocorticoid receptors in adrenalectomized
Dahl salt-sensitive rats.
AB - We previously showed that selective mineralocorticoid receptor (MR) blockade by
eplerenone is cardioprotective in Dahl salt-sensitive (DS) rats. To clarify the
consequences of glucocorticoid-mediated MR activation in these animals, we
investigated the effects of exogenous corticosterone on blood pressure as well as
cardiac remodeling and function after adrenalectomy. DS rats were subjected to
adrenalectomy at 6 weeks of age and thereafter fed a high-salt diet and
administered corticosterone (20 mg/kg per day) or vehicle. Systolic blood
pressure was higher in the corticosterone group than in the vehicle group at 7
weeks and thereafter. By 11 weeks, corticosterone had reduced left ventricular
(LV) mass and induced LV diastolic dysfunction. The ratio of collagen type I to
type III mRNA levels in the left ventricle was increased in the corticosterone
group compared with the vehicle group. Administration of a non-antihypertensive
dose of the MR antagonist spironolactone (20 mg/kg per day) from 6 weeks
inhibited the effects of corticosterone on both the collagen type I to type III
mRNA ratio and diastolic function without affecting the decrease in LV mass.
Spironolactone attenuated both the increase in NADPH oxidase activity in the left
ventricle and coronary vascular inflammatory responses apparent in the
corticosterone group. These results indicate that exogenous glucocorticoids
induce hypertension, cardiac remodeling, and diastolic dysfunction in
adrenalectomized DS rats fed a high-salt diet. The cardiac effects of exogenous
glucocorticoids are likely attributable, at least in part, to myocardial
oxidative stress and coronary vascular inflammation induced by glucocorticoid
activated MRs.
PMID- 25129994
TI - Unexpected ovarian malignancy found after laparoscopic surgery in patients with
adnexal masses--a single institutional experience.
AB - Laparoscopy has become the standard surgery for the treatment of benign ovarian
tumors. The aim of this study was to evaluate the appropriateness of laparoscopy
for ovarian tumors, including those with malignant potential. A total of 487
patients with adnexal masses underwent laparoscopic surgery in Social Insurance
Chukyo Hospital from January 2000 to December 2012. We reviewed 471 cases that
fulfilled the criteria set for this study, and examined 10 cases with unexpected
ovarian malignancy to analyze their preoperative diagnosis, second surgery,
postoperative chemotherapy, and prognosis. The ages of the 471 patients ranged
from 13 to 50 years, with a median of 31. Nulliparous patients numbered
321(68.1%). Of all, 436 patients mostly consisted of those with endometrioma,
benign ovarian neoplasm or functional cyst. In all, we histologically identified
10 women with malignancy: 6 with borderline ovarian tumors (BOT), 2 with ovarian
cancer, and 2 with histologically rare tumors (immature teratoma and granulosa
cell tumor). All patients with BOT were diagnosed with a mucinous histology. Two
patients underwent both second radical surgery (hysterectomy and contra- or
bilateral salpingo-oophorectomy) and chemotherapies that consisted of CBDCA and
PTX or DTX. Thus, 2 patients underwent staging procedures, but the remaining 8
cases did not. None of them had evidence of recurrences. With accurate staging
and careful postoperative follow-up, laparoscopic surgery could be a feasible
initial operation for patients with adnexal masses including early-stage ovarian
malignancy.
PMID- 25129995
TI - External beam radiotherapy for painful bone metastases from hepatocellular
carcinoma: multiple fractions compared with an 8-Gy single fraction.
AB - External beam radiotherapy (EBRT) for hepatocellular carcinoma (HCC) bone
metastases has not been popular in palliative therapy, and optimum dose schedules
have not been decided because of limited published reports. We here evaluated the
palliative effect of EBRT for HCC bone metastases and compared the dose-response
relationship between multiple fractions (MFs) and an 8-Gy single fraction (SF).
Twenty-eight patients (42 sites) with painful bone metastases who received EBRT
and were analyzed retrospectively. Eight patients (12 sites) received SF. Of the
remaining 20 patients (30 sites), 10 received MFs at moderate doses (20-30 Gy; 17
sites) and 10 received MFs at high doses (36-52 Gy; 13 sites). Overall response
was achieved at 83% (35) of all sites; 75% (9) and 87% (26) for the SF and MF
patients (88%, moderate dose; 85%, high dose), respectively. No significant
differences in overall response were observed between each fraction schedule.
Response duration was significantly longer for the high-dose MF patients than for
the SF patients and moderate-dose MF patients (P < 0.05). SF was as effective as
MF radiotherapy in terms of pain relief, but high-dose MF delivery relieved pain
for a significantly longer duration.
PMID- 25129996
TI - The results of volar locking plate fixation for the fragility fracture population
with distal radius fracture in Japanese women.
AB - The purpose of this study was to determine whether volar locking plate fixation
for distal radius fracture benefits the fragility fracture population as much as
it benefits the non-fragility fracture population. This matched case-control
study was conducted based on a multi-center clinical prospective cohort. A
comparison of treatment outcomes after volar locking plate fixation was made
between females 55 years of age and older (fragility fracture population) and
males less than 75 years of age (non-fragility fracture population) by evaluating
clinical, radiological, and subjective outcomes using Hand20, a validated patient
rated disability instrument. A total of 170 patients were enrolled in this study.
The two cohorts were matched in terms of AO fracture type. The fragility fracture
population group and the non-fragility fracture population group each consisted
of 50 patients. All objective measurements including wrist range of motion and
radiological evaluations, but excluding grip strength, were not significantly
different between the two groups. However, the Hand20 at 18 months after surgery
was worse in the fragility fracture population group than in the non-fragility
fracture population group. Carpal tunnel syndrome was the most frequently
encountered complication in the fragility fracture population group, with one
case (2%) in the non-fragility fracture population group and six cases (12%) in
the fragility fracture population group, but the difference was not significant.
In conclusion, there was a significant deficit in the improvement in disability
despite favorable radiological and functional outcomes in fragility fracture
population patients. Therefore, the fragility fracture population, especially
middle-aged or older women, needs to be informed about prolonged disability and
the higher risk of upper extremity disorders prior to surgery.
PMID- 25129997
TI - Polymorphisms of Nrf2, an antioxidative gene, are associated with blood pressure
in Japanese.
AB - Nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a transcription
factor that regulates the expression of antioxidant genes by activating Nrf2
antioxidant response element (ARE) pathway. This study aimed to investigate
association of Nrf2 gene single nucleotide polymorphisms (SNPs), rs35652124 (A -
> G) and rs6721961 (C --> A), with various laboratory data in 464 health
evaluation examinees. The genotyping of these SNPs was performed using polymerase
chain reaction with confronting two-pair primers (PCR-CTPP) assay. The genotype
frequencies of rs35652124 SNP were 21.1% for AA, 44.0% for AG, and 34.9% for GG.
The frequency of A allele was 0.431. In male subjects, cholinesterase was
significantly high, and HDL cholesterol was significantly low in (AG+GG)
carriers. In female subjects, diastolic blood pressure (BP) was significantly low
in (AG+GG) carriers. The genotype frequencies of rs6721961 SNP were 55.2% for CC,
34.7% for CA, and 10.1% for AA. The frequency of A allele was 0.275. In male
subjects, systolic BP, diastolic BP and cholinesterase were significantly low,
and iron was significantly high in (CA+AA) carriers. In female subjects,
cholinesterase was significantly high in (CA+AA) carriers, and diastolic BP was
significantly high in AA carriers. In conclusion, Nrf2 polymorphisms are
associated with BP in Japanese.
PMID- 25129998
TI - A long-term follow-up of patients with retinopathy of prematurity treated with
photocoagulation and cryotherapy.
AB - To evaluate the refractive characteristics of adults diagnosed with retinopathy
of prematurity (ROP) treated with ablation treatment as children, we measured
best corrected visual acuity (BCVA, logMAR), spherical equivalent refraction
(SER), axial length (AL), lens thickness (LT), anterior chamber depth (ACD) and
the corneal curvature radius (CCR) from 46 eyes, 24 patients (15-30 years old)
that were diagnosed with ROP. Patients were divided into two groups dependent on
the size of the treated retina at the time of ablation treatment; i.e., 360
degrees group (treatment over the whole circumference of the retina; n = 18) and
partial group (treatment over part of the retina; n = 28). The study showed that
LT was significantly larger (P < 1x10(-4)) and ACD was significantly shorter (P <
1 x 10(-3)) in 360 degrees group (4.26 +/- 0.40 mm and 2.92 +/- 0.48 mm,
respectively) than those in partial group (3.71 +/- 0.34 mm and 3.42 +/- 0.26 mm,
respectively). However, there were no differences in SER (-6.52 +/- 3.54 diopter
vs. -5.95 +/- 4.12 diopter, P = 0.31), AL (23.9 +/- 1.42 mm vs. 25.0 +/- 21.48
mm, P = 0.08) and CCR (7.59 +/- 0.37 mm vs. 7.59 +/- 0.19 mm, P = 0.86). These
results indicated that the eyes in the 360 degrees group had larger LTs but did
not have extended ALs compared with the partial group.
PMID- 25129999
TI - Factors associated with early postpartum maternity blues and depression tendency
among Japanese mothers with full-term healthy infants.
AB - Maternity blues and postpartum depression are common mental health problems
during the early postpartum period. However, few studies have examined the
factors associated with maternity blues and postpartum depression in healthy
mothers with spontaneous births of healthy full-term infants. This study aimed to
determine the demographic and obstetric factors, various feelings during
pregnancy, and psychological factors by using the Maternity Blues Scale (MBS) and
Edinburgh Postnatal Depression scale (EPDS) among healthy Japanese mothers. We
distributed the MBS and EPDS self-administered questionnaires to 100 Japanese
mothers during their 4-5 day hospitalization and at a health check-up 1-month
after delivery, respectively. Multiple regression analyses were performed
including the above-mentioned variables as independent variables and the maximum
MBS or EPDS scores as dependent variables. The answers "Having a friend I can
talk to about maternity life or child rearing" [beta (95% confidence interval) =
1.53 (-2.68 - -0.378)] and "Satogaeri bunben", a Japanese traditional support
system wherein a postnatal woman lives with her husband/parents [-2.82 (-4.73 -
0.898)] were significantly associated with MBS scores. The answer "Having a
friend I can talk to about maternity life or child rearing" [-2.83 (-4.76 -
0.903)] was also significantly associated with EPDS scores, although the
association between the partner's age and these scores was marginally significant
[-0.106 (-0.008 - 0.221)]. This study shows that it is important to provide
support for healthy women without delivery complications, both at home and in the
community.
PMID- 25130000
TI - Biochemical staging of the chronic hepatic lesions of Wilson disease.
AB - BACKGROUND: Copper toxicity steadily affects the livers of patients with Wilson
disease. However, the toxic effect of copper on serum aspartate and alanine
aminotransferase levels remains to be clarified as a prerequisite for diagnostic
tests. The clinical records of 33 cases were analyzed to clarify the natural
history of Wilson disease. Phenotypes were simplified into hepatic, acute, and
neurologic. The bio-low stage of both enzymes was less than 40 IU/L, the bio
moderate stage was intermediate between 40 and 200 IU/L, and the bio-high stage
was more than 200 IU/L of either or both enzymes. Rebounded enzyme levels at the
recovery period from anemia were presumed to be the chronic baselines when pre
anemic enzyme levels were not available in the acute phenotype. We investigated
whether these enzyme levels may provide information useful for screening
patients. The natural history of chronic Wilson disease consisted of the first
increasing and second decreasing phases. The clinical courses of a 4-year-old boy
and 12-year-old girl were representative of the 2 phases, respectively. All but
one patient were in the decreasing phase. Negative correlations were obtained
between age and enzyme level in the decreasing phase. The hepatic phenotype may
be a prototype found throughout the 2 phases, and acute and neurologic phenotypes
may be major complications in the bio-moderate and bio-low stages of the
decreasing phase, respectively. Biochemical staging may provide a better
understanding of Wilson disease when combined with phenotypes. Bio-high stage
patients should be referred to a medical center for diagnosis.
PMID- 25130001
TI - Rat model demonstrates a high risk of tremolite but a low risk of anthophyllite
for mesothelial carcinogenesis.
AB - Asbestos was abundantly used in industry during the last century. Currently,
asbestos confers a heavy social burden due to an increasing number of patients
with malignant mesothelioma (MM), which develops after a long incubation period.
Many studies have been conducted on the effects of the asbestos types that were
most commonly used for commercial applications. However, there are few studies
describing the effects of the less common types, or minor asbestos. We performed
a rat carcinogenesis study using Japanese tremolite and Afghan anthophyllite.
Whereas more than 50% of tremolite fibers had a diameter of < 500 nm, only a
small fraction of anthophyllite fibers had a diameter of < 500 nm. We
intraperitoneally injected 1 or 10 mg of asbestos into F1 Fischer-344/Brown
Norway rats. In half of the animals, repeated intraperitoneal injections of
nitrilotriacetate (NTA), an iron chelator to promote Fenton reaction, were
performed to evaluate the potential involvement of iron overload. Tremolite
induced MM with a high incidence (96% with 10 mg; 52% with 1 mg), and males were
more susceptible than females. Histology was confirmed using
immunohistochemistry, and most MMs were characterized as the sarcomatoid or
biphasic subtype. Unexpectedly NTA showed an inhibitory effect in females. In
contrast, anthophyllite induced no MM after an observation period of 550 days.
The results suggest that the carcinogenicity of anthophyllite is weaker than
formerly reported, whereas that of tremolite is as potent as major asbestos as
compared with our previous data.
PMID- 25130002
TI - Dimensions of women's empowerment and their influence on the utilization of
maternal health services in an Egyptian village: a multivariate analysis.
AB - This study investigated the association between women's empowerment and the
utilization of maternal health services by women in Egypt and analyzed the
dimensions of women's empowerment that are associated with increased health
service utilization. A cross-sectional survey was conducted in a village in Egypt
in November 2007. A total of 189 women, who had ever been married and had at
least one child, were interviewed to collect data on the utilization of maternal
health services, such as the number of antenatal care (ANC) visits during their
pregnancies and whether delivery of their child was attended by skilled health
personnel. Proxy variables on five different dimensions of women's empowerment
were obtained by principal component analysis, and were tested for an association
with the utilization of maternal health services, using logistic regression
models. The five dimensions extracted from the data were freedom of movement,
economic security and stability, support by family and freedom from domination,
decision-making in daily life, and relationship with the community/participation
in society. Among these dimensions, support by family and freedom from domination
was the only factor that was positively associated with maternal health service
utilization (regular ANC: OR = 1.38, P = 0.05; deliveries assisted by skilled
health personnel: OR = 1.71, P = 0.01). Current age was also associated with the
latter, possibly influenced by the recent rapid increase in the provision of
health services in the village studied. Furthermore, this study revealed that a
relatively high proportion of younger women still only limited access to maternal
health services in Egypt.
PMID- 25130004
TI - Human laryngitis caused by Clinostomum complanatum.
AB - A 64-year-old Japanese man visited our outpatient department complaining of an
irritable sensation in the throat, occurring two days after eating raw freshwater
fish (carp sashimi) at a Japanese-style inn. During laryngeal endoscopy, a slow
moving worm (fluke) was found attached to the surface of the right aryepiglottic
fold. After inhalation of 4% lidocaine, the fluke was removed using endoscopic
forceps. Patient's throat symptoms immediately improved. The worm was
microscopically identified as Clinostomum complanatum. C. complanatum is a
digenetic trematode that usually infects fish-eating water birds. Clinostomum
infections in humans are rare, and only 21 cases have been described in Japan and
Korea. C. complanatum infection is known to occur after eating raw freshwater
fish, which is a secondary intermediate host. In humans, the metacercariae are
released into the stomach and migrate through the esophagus before lodging in the
throat. Primary therapy involves endoscopic removal of the worm.
PMID- 25130003
TI - Multidisciplinary management of small cell carcinoma of the breast: a case
report.
AB - We report a case of primary small cell carcinoma (SCC) of the breast in a 59-year
old female. To the best of our knowledge, there are only 44 cases of this disease
reported in the English literature. The patient also had regional nodal
metastases, but no distant metastases. She underwent neoadjuvant chemotherapy
according to a regimen of pulmonary SCC, and combination of cisplatin and
etoposide (CDDP+VP16). The tumor partially responded to neoadjuvant chemotherapy.
The treatment was followed by modified radical mastectomy and adjuvant
chemotherapy, i.e., EC therapy (epirubicin and cyclophosphamide). She was also
administered in total 50 Gy of radiation treatment to the chest wall. At this
writing, the patient has evidenced no recurrence 36 months after her diagnosis.
PMID- 25130006
TI - Chronic spontaneous lumbar epidural hematoma simulating extradural spinal tumor:
a case report.
AB - Spinal epidural hematoma (SEH) is an uncommon disorder, and chronic SEHs are
rarer than acute SEHs. However, there is few reported involving the bone change
of the vertebral body in chronic SEHs. We present a case report of lumbar
epidural hematoma that required differentiation from extramedullary spinal tumors
by a long process because the CT scan revealed scalloping of the vertebral body
and review the relevant literature. A 78-year-old man had experienced a gradual
onset of low back pain and excruciating pain in both legs. Lumbar MRI on T1
weighted images revealed a space-occupying lesion with a hyperintense signal
relative to the spinal cord with no enhancement on gadolinium adminisration.
Meanwhile, T2-weighted images revealed a heterogeneous intensity change,
accompanying a central area of hyperintense signals with a hypointense peripheral
border at the L4 vertebra. Moreover, the CT scan demonstrated scalloping of the
posterior wall of the L4 vertebral body which is generally suspected as the CT
finding of spainal tumor. During the epidural space exploration, we found a dark
red-colored mass surrounded by a capsular layer, which was fibrous and adhered to
the flavum and dura mater. Microscopic histological examination of the resected
mass revealed a mixture of the relatively new hematoma and the hematoma that was
moving into the connective tissue. Accordingly, the hematoma was diagnosed as
chronic SEH. The particular MRI findings of chronic SEHs are helpful for making
accurate preoperative diagnoses of this pathology.
PMID- 25130005
TI - Gamma knife radiosurgery of brain metastasis from malignant pleural mesothelioma-
report of three cases with autopsy study in a case.
AB - The median survival time of malignant pleural mesothelioma (MPM) has been 9
months. Given the short survival, there have been only few cases in which brain
metastases have been diagnosed and treated before death. Three cases of brain
metastases treated by gamma knife radiosurgery (GKR) are reported. Case I showed
a metastatic lesion in the right frontal lobe which was treated by GKR two years
after diagnosis of MPM. The lesion markedly reduced and the symptoms were
improved, But the patient died of progression of pleural tumor four months after
GKR. A year and three months after the diagnosis, asymptomatic bifrontal lesions
were treated with GKR. However, Case 2 died of abdominal mass a month after. Case
3 showed headache one and half year after the diagnosis. Three brain lesions were
treated by GKR, which disappeared in 4 months. The patient died of new multiple
brain metastases and periventricular dissemination seven months after. The
autopsy revealed a MPM occupying the left pleural cavity. No neoplastic lesion
was found in gamma knife-treated sites. The cause of death was the mass effect by
new metastatic lesions. GKR was found effective also for the treatment of brain
metastasis of MPM.
PMID- 25130007
TI - Intraoperative migration of the trial femoral head into the pelvis during total
hip arthroplasty--report of two cases.
AB - Various complications occur during total hip arthroplasty (THA). It is common to
implement trial treatments of various implants during THA. Here we report on 2
cases in which the trial femoral head fell into the pelvis and migrated during
THA. The trial head was not retrieved but left inside in one case, while the
other presented the opportunity for a possible retrieval. It is important to
recognize the existence of such rare complications.
PMID- 25130008
TI - Partial necrosis of the lunate after a translunate palmar perilunate fracture
dislocation.
AB - We present an extreme rare case of traumatic partial avascular necrosis of the
lunate after palmar perilunate dislocation with lunate fracture. A 32-year-old
female was injured by motorcycle accident with palmar perilunate fracture
dislocation and lunate fracture. Scapholunate and lunotriquetrum dislocations
were reduced and fixed temporarily. The torn dorsal ligament was repaired.
Considering close observation with both arthroscopy and fluoroscopy, we decided
not to conduct open reduction and internal fixation for the lunate. Partial
avascular necrosis of the lunate appeared gradually in follow-up.
PMID- 25130009
TI - Recurrence of solitary fibrous tumor of the cervical spinal cord.
AB - Solitary fibrous tumor (SFT) mostly originates from the pleura because of
proliferation of fibroblast cells. It is extremely rare for the tumor to
originate from the spinal cord. Here, we report a rare case of SFT in the spinal
cord that recurred repeatedly and progressed from intramedullary to
extramedullary. A 40-year-old man underwent C4-5 intramedullary and
extramedullary tumor resection in another hospital. Eighteen years later, he
experienced symptoms of myelopathy because of tumor recurrence; therefore, he
consulted with our hospital and underwent tumor resection again. During surgery,
we found that the tumor had an intramedullary and extramedullary location. Only
partial resection was possible because of intraoperative deterioration in the
compound motor action potential (CMAP). After resection, the pathological
diagnosis was SFT. The postoperative course was good. However, two years later, a
third tumor resection was required because of dysuria and tumor growth. In this
surgery, total resection of the tumor was possible without intraoperative
deterioration of the CMAP. The tumor has not subsequently recurred. However, SFT
recurrence is relatively common and careful follow-up is required for early
detection of recurrence, even after successful removal of the tumor.
PMID- 25130011
TI - Medical identity theft: prevention and reconciliation initiatives at
Massachusetts General Hospital.
AB - BACKGROUND: Medical identity theft refers to the misuse of another individual's
identifying medical information to receive medical care. Beyond the financial
burden on patients, hospitals, health insurance companies, and government
insurance programs, undetected cases pose major patient safety challenges.
Inaccuracies in the medical record may persist even after the theft has been
identified because of restrictions imposed by patient privacy laws. Massachusetts
General Hospital (MGH; Boston) has conducted initiatives to prevent medical
identity theft and to better identify and respond to cases when they occur.
METHODS: Since 2007, MGH has used a notification tree to standardize reporting of
red flag incidents (warning signs of identity theft, such as suspicious personal
identifiers or account activity). A Data Integrity Dashboard allows for tracking
and reviewing of all potential incidents of medical identity theft to detect
trends and targets for mitigation. An identity-checking policy, VERI-(Verify
Everyone's Identity) Safe Patient Care, requires photo identification at every
visit and follow-up if it is not provided. RESULTS: Data from MGH suggest that an
estimated 120 duplicate medical records are created each month, 25 patient
encounters are likely tied to identity theft or fraud each quarter, and 14
patients are treated under the wrong medical record number each year. As of
December 2013, 80%-85% of patients were showing photo identification at
appointments. CONCLUSION: Although an organization's policy changes and
educational campaigns can improve detection and reconciliation of medical
identity theft cases, national policies should be implemented to streamline the
process of correcting errors in medical records, reduce the financial
disincentive for hospitals to detect and report cases, and create a single point
of entry to reduce the burden on individuals and providers to reconcile cases.
PMID- 25130010
TI - A case of mediastinal embryonal carcinoma successfully treated by integrative
therapy.
AB - Mediastinal embryonal carcinoma is rare, and the life prognosis of this disease
is assumed to be relatively short. We encountered a case of mediastinal embryonal
carcinoma for which we could perform radical surgical resection. The patient was
male, aged 16 years, and acutely aware of back pain. Because the pain increased
during the same year, he visited a local doctor, and an expanding neoplastic
lesion was detected in the right thoracic wall by computed tomography (CT). Then
he was referred to our institution. Magnetic resonance imaging (MRI) showed a
dumbbell type tumor (Eden type 3) at the Th7/8 level. Malignant disease was
suspected, so the authors planned and performed CT-guided biopsy. The result
showed that this tumor pathologically corresponded to malignant peripheral nerve
sheath tumor (MPNST). Therefore, chemotherapy was considered the main treatment.
After 2 courses of chemotherapy, the tumor size decreased dramatically. The
authors thought that radical resection is possible if there is no intrathoracic
tumor dissemination as a result of a favorable response to chemotherapy. We thus
perfomed surgical resection after we confirmed by a thoracoscopic exploratory
thoracotomy that there was no intrathoracic tumor dissemination. Pathological
findings were consistent with an embryonal carcinoma. Both the cutting ends of
the thoracic wall and the epidural lateral sides of the excised lesion were
negative for tumor cells. There is no image finding from the MRI and PET-CT
suggesting metastasis or recurrence in the MRI and PET-CT 18 months after
surgical resection. Therefore, the long-term vital prognosis can be expected in
this patient.
PMID- 25130012
TI - A clinical practice agreement between pharmacists and surgeons streamlines
medication management.
AB - BACKGROUND: Collaborative practice agreements (CPAs), which have been widely used
in ambulatory care, were applied to hospital surgical teams in a postsurgical
colorectal surgery unit at Mayo Clinic Rochester (Minnesota). METHODS: The CPA
allowed pharmacists the decision rights to initiate, modify, or discontinue
medications in accordance with the surgical teams' practice standards, evidence
based medicine, and/or institutional policies without specific request and
response from the surgeon/provider. Interventions for CPA and non-CPA groups were
captured from a prospectively maintained database. Admission medication
reconciliation (patient medication list compared with hospital orders) was
compared between CPA patients and non-CPA patients. Time-to-decision and surgical
service interruptions were measured by an audit of 50 CPA interventions versus 50
non-CPA interventions. RESULTS: For the 135 CPA-eligible colorectal and general
surgery patients in January-March 2011, there were 417 pharmacist interventions
(3.1 per patient episode), compared with 537 for 305 non-CPA patients on a
comparable surgical unit (1.8 per patient episode) (p < or = .0200). Admission
medication reconciliation was completed for 135/135 (100%) of CPA patients versus
220/305 (72%) of non-CPA patients (p < or = .001). Rules-based interventions with
CPA totaled 21/417 (5%) versus 221/537 (41%) without CPA (p < or = .0001). The
time-to-decision (CPA versus non-CPA) was within 1 minute versus 0 to 4,320
minutes (mean, 314.2 minutes; median, 138 minutes), respectively (p = .0063).
CONCLUSION: The CPA increased pharmacist interventions and increased both
accuracy and efficiency in resolving medication-related problems. The CPA
streamlined and improved medication management of hospitalized surgical patients.
PMID- 25130013
TI - Walkrounds in practice: corrupting or enhancing a quality improvement
intervention? A qualitative study.
AB - BACKGROUND: Walkrounds, introduced as Leadership (or Executive) WalkRounds, are a
widely advocated model for increasing leadership engagement in patient safety to
improve safety culture, but evidence for their effectiveness is mixed. In the
English National Health Service (NHS), hospitals have been strongly encouraged to
make use of methods closely based on the walkrounds approach. A study was
conducted to explore how walkrounds are used in practice and to identify
variations in implementation that might mediate their impact on safety and
culture. METHODS: The data, collected from 82 semistructured interviews in the
English NHS, were drawn from two components of a wider study of culture and
behavior around quality and safety in the English system. Analysis was based on
the constant comparative method. FINDINGS: Our analysis highlights how local,
pragmatic adjustments to the walkrounds approach could radically alter its
character and the way in which it is received by those at the front line. The
modification and expansion of walkrounds to increase the scope of knowledge
produced could increase the value that executives draw from them. However, it
risks replacing the main objectives of walkrounds--specific, actionable knowledge
about safety issues, and a more positive safety culture and relationship between
ward and board--with a form of surveillance that could alienate frontline staff
and produce fallible insights. CONCLUSION: The studys findings suggest some
plausible explanations for the mixed evidence for walkrounds' effectiveness in
creating a safety culture. On a practical level, they point to critical questions
that executives must ask themselves in practicing interventions of this nature to
ensure that adaptations align rather than conflict with the intervention's model
of change.
PMID- 25130014
TI - Barriers and facilitators for taking action after classroom-based crew resource
management training at three ICUs.
AB - BACKGROUND: Given growing awareness of the crucial role of nontechnical skills in
providing safe patient care, crew resource management (CRM) training is being
increasingly used to improve them. Implementing the plans of action that are
formulated during CRM training may constitute an important first step in the
successful uptake of skills. Accordingly, understanding the factors that
determine why participants do or do not carry out those plans should help improve
CRM training and enhance its impact. A study was conducted to examine the impact
of pretraining readiness factors and posttraining barriers and facilitators on
follow-up on plans of action. METHODS: Three ICUs, each at a different
nonacademic teaching hospital in The Netherlands, received two-day classroom
based CRM training in 2010. During the training, new ideas for safety initiatives
were documented as concrete plans of action. All plans were categorized as
individual (for example, "Always ask a colleague to double-check your
medication"), team, or organizational. Two months before and three months after
the CRM training, all ICU employees were asked to fill out a set of
questionnaires. RESULTS: Management support for patient safety before the
training was a positive determinant of the number of perceived facilitators. A
significant relationship was found between the perceived barriers and
facilitators after CRM training and Taking Action. More barriers were negatively
associated, while more facilitators were positively associated, with Taking
Action. When assessed separately, none of the readiness factors were
significantly associated with taking action, while when assessed together, the
readiness factors were positive related to Taking Action. DISCUSSION: To overcome
the barriers and profit from the facilitators, they should be considered during
the training and in regular CRM meetings afterward.
PMID- 25130015
TI - Improving the quality of care and communication during patient transitions: best
practices for urgent care centers.
AB - BACKGROUND: Although high-quality care transitions require timely and accurate
communication of clinical information between providers, such communication is
inconsistent, and there are few established guidelines outside the hospital
setting. METHODS: Using a systematic, collaborative quality improvement process,
Healthcentric Advisors (Providence, Rhode Island) undertook a multistage approach
to define best practices for care transitions in the urgent care setting. This
approach entailed review of the medical literature to identify processes that
improve care transitions outcomes, gathering of information about clinicians'
preferences, and a statewide community meeting with urgent care clinicians and
other stakeholders to vet draft guidelines and obtain consensus on the concepts.
RESULTS: Because of an inability to identify any guidelines or research that
globally addressed care transitions from the urgent care setting, information was
gathered from studies on patient discharge instructions and extrapolated from the
evidence base available for related settings. The resulting set of eight best
practices for urgent care center transitions focuses on clinician-to-clinician
communication and patient activation, which can be implemented to establish
measurable, communitywide expectations for communication. CONCLUSION: This set of
best practices constitutes the first known guidelines to establish expectations
and measures tailored specifically to transitions from the urgent care setting to
the emergency department or primary care office. They can serve as a resource and
a framework for urgent care clinicians expanding their collaboration with
community partners, such as emergency departments and primary care providers,
particularly in the context of emerging payment models.
PMID- 25130016
TI - A medication-based trigger tool to identify adverse events in pediatric
anesthesiology.
PMID- 25130017
TI - A situational analysis of priority disaster hazards in Uganda: findings from a
hazard and vulnerability analysis.
AB - BACKGROUND: Most countries in sub-Saharan Africa have not conducted a disaster
risk analysis. Hazards and vulnerability analyses provide vital information that
can be used for development of risk reduction and disaster response plans. The
purpose of this study was to rank disaster hazards for Uganda, as a basis for
identifying the priority hazards to guide disaster management planning. METHODS:
The study as conducted in Uganda, as part of a multi-country assessment. A
hazard, vulnerability and capacity analysis was conducted in a focus group
discussion of 7 experts representing key stakeholder agencies in disaster
management in Uganda. A simple ranking method was used to rank the probability of
occurance of 11 top hazards, their potential impact and the level vulnerability
of people and infrastructure. RESULTS: In-terms of likelihood of occurance and
potential impact, the top ranked disaster hazards in Uganda are: 1) Epidemics of
infectious diseases, 2) Drought/famine, 3) Conflict and environmental degradation
in that order. In terms of vulnerability, the top priority hazards to which
people and infrastructure were vulnerable were: 1) Conflicts, 2) Epidemics, 3)
Drought/famine and, 4) Environmental degradation in that order. Poverty, gender,
lack of information, and lack of resilience measures were some of the factors
promoting vulnerability to disasters. CONCLUSION: As Uganda develops a disaster
risk reduction and response plan, it ought to prioritize epidemics of infectious
diseases, drought/famine, conflics and environmental degradation as the priority
disaster hazards.
PMID- 25130018
TI - Institutional frameworks for management of epizoonotic emergencies in six
countries in the Eastern Africa region: a situational analysis.
AB - INTRODUCTION: The Eastern Africa region is a hot-spot for epidemics of emerging
zoonotic diseases ('epizoonotics'). However, the region's capacity for response
to epidemics of zoonotic origin has not been documented. This paper presents a
multi-country situational analysis on the institutional frameworks for management
of zoonotic epidemics in the Eastern Africa region. METHODS: A multi-country
assessment of 6 country teams was conducted (Uganda, Kenya, Tanzania, Ethiopia,
DRC and Rwanda). It involved a review of records and interviews with key
informants from agencies with a stake in the management of zoonotic and disasters
in general in the respective countries. Qualitative data were analyzed for key
emerging themes. FINDINGS: There are many socio-cultural risk factors to epidemic
prone zoonotic diseases in the region. Countries have varying levels of
preparedness for zoonotic emergencies. All 6 countries have a framework for
disaster management. However, technical response to epidemics is managed by the
line sectors, with limited Inter-sectoral collaboration. Some sectors were
disproportionately more prepared than others. Surveillance systems are mostly
passive and inadequate for early detection. All 6 countries have built reasonable
capacity to respond to avian influenza, but not other zoonotic emergencies. Most
countries lack personnel at the operational levels, and veterinary public health
services are ill-facilitated. CONCLUSION: There is need to strengthen veterinary
public health services at all levels, but with a 'one health' approach. There is
also need to establish 'risk-based surveillance' hot spots for zoonotic epidemics
and to build community resilience 'epizoonotic' diseases.
PMID- 25130019
TI - A descriptive overview of the burden, distribution and characteristics of
epidemics in Uganda.
AB - BACKGROUND: Although Uganda is a high burden country for epidemics of infectious
diseases, the pattern of epidemics has not yet been adequately documented. The
purpose of this study was to describe the distribution, magnitude and
characteristics of recent epidemics in Uganda, as a basis for informing policy on
priorities for targeted prevention of epidemics. METHODS: Qualitative and
quantitative data was collected from the Epidemiological Surveillance Division of
the Ministry of Health and the African Field Epidemiology Network through key
informant interviews and a documents review. RESULTS: Acute outbreaks that have
occurred since 2002 are: Cholera, Meningitis, Malaria, Viral Hemorrhagic Fevers
(Ebola, Marburg), arboviruses (yellow-fever), Anthrax, Hepatitis E, Measles,
Polio, Influenza A viruses, dysentery and other diarrheal diseases. Chronic
outbreaks include: Propagated epidemics of cholera, head nodding disease,
Hepatitis B, Hepatitis E, HIV and Typhoid Fever. Thirty-one districts had a high
incidence of cholera. Most of the epidemic prone diseases are preventable through
appropriate behavior change and sanitation measures. However, current focus is
mainly on prevention, low focus on prevention. Community involvement in
resilience and early detection is inadequate. CONCLUSION: Uganda has a high
burden of preventable epidemic prone diseases. There is need to invest in
surveillance, early detection and sustainable prevention through appropriate
technology and behavior change involving individuals, families, communities and
policy makers.
PMID- 25130020
TI - Opportunities for strategic use of e-learning in scaling up disaster management
capacity in Eastern Africa: a descriptive analysis.
AB - BACKGROUND: The growing need for disaster management skills at all levels in
Eastern Africa requires innovative approaches to training planners at all levels.
While information technology tools provide a viable option, few studies have
assessed the capacity for training institutions to use technology for cascading
disaster management skills. METHODS: The design was an explorative survey. A pre
training survey was conducted among 16 faculty members (9 academic staff and 7
information technology (IT) staff) from 7 schools of public health in Eastern
Africa. Key informant interviews with 4 students and 4 staff members were
conducted at the school of public health in Makerere. IT staff also conducted
observations on trends of use of information technology infrastructure. RESULTS:
Current levels of use of ICT among teaching and IT staff is variable. On-site use
of the internet is high, but off-site access is low. Personal computers, e-mail,
discussion forums and other web-based learning management platforms and open
education resources (OERs) have been variably used by faculty and students to
facilitate learning. On the other hand, videos, web-conferencing, social media,
web-based document management tools, and mobile telephone applications were much
less frequently used. A disaster management short course produced by the Health
Emergencies Management Project (HEMP) has been adapted to a web-based open
education resource and an interactive CD-ROM. Challenges included low levels of
awareness and skills in technology options among students and faculty and access
to reliable internet. CONCLUSIONS: Despite the existing challenges, technology
tools are a viable platform for cascading disaster management skills in Eastern
Africa.
PMID- 25130022
TI - Achievements and challenges of resource allocation for health in a decentralized
system in Tanzania: perspectives of national and district level officers.
AB - OBJECTIVE: The goal of this study was to identify the achievements and challenges
of a resource allocation process in a decentralized health system in Tanzania as
they are perceived by national and district level officers. METHODOLOGY: This
study was conducted between May 2011 and July 2012 in two districts of Dodoma
region: Kongwa and Bahi. Data were collected from 25 key people involved in
policy, planning and management aspects for the allocation of financial resources
from the central government to local government districts. Thus, the recruitment
of the study participants was purposive, as it took account of their positions
and experience in health resource allocation and management. The data were
collected through conversation in face-to-face in-depth interviews with the
officers concerned. The data were analysed manually using qualitative content
analysis. RESULTS: The study has identified the achievements and challenges of
resource allocation in a decentralized health system of Tanzania. The
achievements include: the design and use of a needs-based resource allocation
formula; reduced resource allocation inequalities between rural and urban
districts; and a wide discretion by the district council to mobilize and utilize
health insurance funds and user fees. On the other hand, the challenges are: the
disbursed funds fall far short of centrally determined budget ceilings, and the
funds are sent late; Council Health Management Teams (CHMT) develop budgets but
are restricted on the percentage they can allocate to different areas--so there
is severe under-funding of disease prevention and health promotion initiatives at
the community level. CONCLUSION: This study has identified achievements that
should be further nurtured and challenges that should be worked on for the
improvement of the decentralized health system. Thus, as a way forward, it is
recommended that the equitable allocation of resources should go beyond the
recurrent costs for the delivery of health services.
PMID- 25130021
TI - Hazard analysis of Arid and semi-Arid (ASAL) regions of Kenya.
AB - INTRODUCTION: This paper describes a situationanalysis on hazards in the Arid and
semi-Arid lands of Kenya. The leading hazards affecting the Arid and semi-arid
lands are mainly natural and include among others drought, floods, and
landslides. Other hazards of importance were found to be war and conflict,
HIV/AIDS and fires. Over 80% of these are weather related. OBJECTIVES: The
overall objective of this study was to prioritize hazards in the ASAL region.
Specifically, the study identified the top ten hazards in the ASAL Districts of
Kenya, determined Probability of occurrence; Analyzed the potential impact of the
hazard and utilizing multiplier effect prioritized the Hazards using a
hypothetical model. METHODOLOGY: This was a descriptive study conducted in over
half of the Kenya's ASAL Districts in four regions of Lower and Upper Eastern,
North Eastern and part of the Coast region. Six Districts were purposively
selected per region with six officers from each District all totaling one hundred
and forty four. The sectors where respondents were sourced from were Agriculture,
Health, local Government, and Provincial Administration, Environment and NGO. The
members through a consensus process analyzed hazards in groups of their
respective districts using a tool that had been developed and respondents trained
on its use. RESULTS: One hundred and forty four (144) officers from Twenty four
Districts in the four regions were recruited. One hundred twenty seven (81%) were
male and only 27 (19% ) were female The representation of participants per sector
was Governance 25% followed by Civil society organizations 21%, Health 16%,
Agriculture and arid lands 15%, Research and scientific institutions 13%. The top
Priority Hazards identified using the mean score were Drought and famine (5.4)
Epidemics and epizootics (3.8), HIV/AIDS (3.6), War and conflict (2.5), Floods
(2.5) CONCLUSIONS: The exercise confirmed the priority hazards in the Arid and
semi-arid regions of Kenya and described vulnerability factors that included
water scarcity, poverty and low educational levels. The region suffers from a
variety of hazards in particular Drought and famine, Epidemics including HIV/AIDS
and War and conflict. Environmental degradation though given a low score may be
more of a perception. There is need to undertake a comprehensive hazard and
Vulnerability analysis at regional and country level to inform interventions and
other developmental activities. Women should be targeted at the community and
leadership level, and efforts to empower them should be stepped up.
PMID- 25130023
TI - Prioritization of disasters and their management in Rwanda.
AB - INTRODUCTION: Rwanda has been experiencing quite a significant number of
disastrous events of both natural and man-made origin in the last 2 decades. Many
cases of disasters are particularly linked to the geographic, historical and
socio-cultural aspects of the country. The overall objective of the present
article is to perform a situation analysis of disasters in Rwanda and to
highlight the institutional and legal framework of disaster management. METHODS:
An assessment questionnaire focused on the current capacity, institutional
frameworks and on-going initiatives for disaster management at country level and
operational level was administered. The assessment was descriptive and used
mainly qualitative methods. These included review of records (country policies
and policy briefs, programme documents), interviews with key informants from line
ministries, and interviews with key informants from stakeholder agencies.
RESULTS: The Rwandan hazard profile, its vulnerability and capacity assessment
shows top seven disasters which are related to epidemics, hails storms/floods;
roads accidents; environmental degradation and earthquakes/volcanic eruption.
Currently, the Institutional framework for disaster management and response is
coordinated by Ministry of Disaster Management and Refugee Affairs through the
Rwanda National Disasters Operation Center. Although disaster risk reduction has
been integrated into sustainable policies and plans, most districts do not have
adequate capacity to plan for disasters and the majority of districts disaster
committees have not yet been trained. CONCLUSION: Rwanda has established a legal
and institutional framework for disasters management. There is a need to build
capacity in disaster management at operational level (District).
PMID- 25130024
TI - Use of the Automated Disaster and Emergency Planning Tool in developing district
level public health emergency operating procedures in three East African
countries.
AB - BACKGROUND: Sub-Saharan Africa is vulnerable to several natural and man-made
disasters. We used the CDC Automated Disaster and Emergency Planning Tool (ADEPT)
to develop all-hazards disaster management plans at district level in three
eastern African countries. METHODS: During July 2008-February 2011, we used the
automated disaster and emergency planning tool to conduct training on disaster
planning and management in the three east African countries namely Kenya,
Tanzania and Uganda. We trained district disaster teams per country. We held 7
trainings in Tanzania, 8 in Uganda and 10 in Kenya respectively. The district
disaster management teams trained comprised five district administrative
personnel and a national Red Cross officer. The training took 5 days. RESULTS: A
total of 100 districts teams (40 in Uganda and 35 in Kenya and Tanzania
respectively) were trained using the ADEPT and consequently 100 district disaster
response plans were developed during 2008-2011. A total 814 district disaster
team members from these districts were trained. Our experience has shown that the
Automated Disaster Emergency Planning Tool is a relatively quick, easy,
practical, participatory and inexpensive approach to developing emergency
operating plans at the sub-national (district) level. CONCLUSIONS: The ADEPT can
be used relatively easily, quickly and inexpensively at the sub-national levels
to develop emergency operating procedures to improve disaster management.
Although the ADEPT enables district disaster response teams to generate their
disaster response plans, the use of the ADEPT may be hampered by lack of computer
skills and knowledge of MS computer programme by district personnel in resource
limited settings.
PMID- 25130025
TI - Regional approach to building operational level capacity for disaster planning:
the case of the Eastern Africa region.
AB - BACKGROUND: The Eastern Africa region is regularly affected by a variety of
disasters ranging from drought, to human conflict and population displacement.
The magnitude of emergencies and response capacities is similar across the
region. In order to strengthen public health disaster management capacities at
the operational level in six countries of the Eastern Africa region, the USAID
funded leadership project worked through the HEALTH Alliance, a network of seven
schools of public health from six countries in the region to train district-level
teams. OBJECTIVES: To develop a sustainable regional approach to building
operational level capacity for disaster planning. METHODS: This project was
implemented through a higher education leadership initiative. Project activities
were spear-headed by a network of Deans and Directors of public health schools
within local universities in the Eastern Africa region. The leadership team
envisioned a district-oriented systems change strategy. Pre-service and in
service curricula were developed regionally and district teams were formed to
attend short training courses. Project activities began with a situational
analysis of the disaster management capacity at national and operational levels.
The next steps were chronologically the formation of country training teams and
training of trainers, the development of a regional disaster management training
curriculum and training materials, the cascading of training activities in the
region, and the incorporation of emerging issues into the training curriculum. An
evaluation model included the analysis of preparedness impact of the training
program. RESULTS: The output from the district teams was the creation of
individual district-level disaster plans and their implementation. This 4-year
project focused on building operational level public health emergency response
capacity, which had not previously been part of any national program. Use of the
all-hazard approach rather than a scenario-based contingency planning led to the
development of a standardized curriculum for training both in-service and pre
service personnel. Materials developed during the implementation phases of the
project have been incorporated into public health graduate curricula in the seven
schools. This systems-based strategy resulted in demonstrable outcomes related to
district preparedness and university engagement in disaster management.
CONCLUSION: University partnerships are an effective method to build district
level disaster planning capacity. Use of a regional network created a
standardized approach across six countries.
PMID- 25130026
TI - Performance of district disaster management teams after undergoing an operational
level planners' training in Uganda.
AB - INTRODUCTION: Uganda is vulnerable to several natural, man-made and a hybrid of
disasters including drought, famine, floods, warfare, and disease outbreaks. We
assessed the district disaster team's performance, roles and experiences
following the training. FINDINGS: The disasters most commonly experienced by the
district teams were epidemics of diseases in humans (7 of 12), animals
(epizoonotics) (3 of 12) and crops (3 of 12); hailstorms and floods (3 of 12).
The capabilities viewed most useful for management of disasters were provision of
health care services (9/12) and response management (8 of 12). The capability
domains most often consulted during the disasters were general response
management (31%), health services (29%) and water and sanitation (17%). The
skills areas perceived to be vital following the training were response to
epidemics 10/12, disaster management planning 8/12, hazards and vulnerability
analysis 7/12 and principles of disaster planning 7/12 respectively. Main
challenges mentioned by district teams were inadequacy of finance and logistics,
lack of commitment by key partners towards disaster preparedness and response.
CONCLUSIONS: The most common disaster experienced disasters related to outbreaks
of diseases in man, animals and crops. The most frequently applied capabilities
were response management and provision of emergency health services. The
activities most frequently implemented following disaster management teams
training were conducting planning meetings, refinement of plans and dissemination
of skills gained. The main challenges were related to limited budget allocations
and legal frameworks for disaster management that should be addressed by both
central and local governments.
PMID- 25130027
TI - A descriptive analysis of the institutional frameworks for disaster management in
Uganda: structures, functions and gaps.
AB - BACKGROUND: There is insufficient documentation of the institutional frameworks
for disaster management and resilience at different levels in sub-Saharan Africa.
The objective of this study was to describe the institutional framework for
disaster management in Uganda, and to identify actionable gaps at the different
levels. METHODS: This was part of a multi-country assessment in which 6 countries
in Eastern Africa developed and applied a common tool. The assessment was
qualitative in nature employing a mixed methods approach including review of
documents, interviews with key informants from agencies involved in disaster
management in Uganda, group discussions with stakeholder and synthesis meetings
of the assessment team. FINDINGS: The Office of the Prime Minister is the lead
agency for disaster management, but management of disasters of a technical nature
is devolved to line ministries (e.g. epidemics by the Health Ministry and
Epizootics by the Agriculture Ministry). A new policy spells out disaster
management structures at national, district, sub-county, and village levels. Key
challenges included coordination, more focus on prevention than risk reduction,
differences in capacity between sectors and inadequate inter-sectoral
collaboration. The new policy and structures have not yet been rolled out to
districts and sub-district levels, and districts lack a line item budget for
disaster capacity building. CONCLUSIONS: The institutional framework for disaster
management in Uganda needs to be strengthened at all levels through initiation of
the relevant structures, training, and resource allocation so that they develop
disaster management plans.
PMID- 25130028
TI - Challenges towards realization of health care sector goals of Tanzania
development vision 2025: training and deployment of graduate human resource for
health.
AB - BACKGROUND: Human resource for health (HRH) is an essential building block for
effective and efficient health care system. In Tanzania this component is faced
by many challenges which in synergy with others make the health care system
inefficient. In vision 2025 the country recognizes the importance of the health
care sector in attaining quality livelihood for its citizens. The vision is in
its 13th year since its launch. Given the central role of HRH in attainment of
this vision, how the HRH is trained and deployed deserves a deeper understanding.
OBJECTIVE: To analyze the factors affecting training and deployment process of
graduate level HRH of three core cadres; Medical Doctors, Doctor of Dental
Surgery and Bachelor of Pharmacy towards realization of development vision 2025.
METHODS: Explorative study design in five training institutions for health and
Ministry of Health and Social Welfare (MoHSW) headquarters utilizing in-depth
interviews, observations and review of available documents methodology. RESULTS:
The training Institutions which are cornerstone for HRH training are
understaffed, underfunded (donor dependent), have low admitting capacities and
lack co-ordination with other key stakeholders dealing with health. The
deployment of graduate level HRH is affected by; limited budget, decision on
deployment handled by another ministry rather than MoHSW, competition between
health care sector and other sectors and lack of co-ordination between employer,
trainers and other key health care sector stakeholders. Awareness on vision 2025
is low in the training institutions. CONCLUSIONS: For the vision 2025 health care
sector goals to be realized well devised strategies on raising its awareness in
the training institutions is recommended. Quality livelihood as stated in vision
2025 will be a forgotten dream if the challenges facing the training and
deployment of graduate level HRH will not be addressed timely. It is the authors'
view that reduction of donor dependency syndrome, extension of retirement age for
academic Staffs in the training institutions for health and synergizing the
training and deployment of the graduate level HRH can be among the initial
strategies towards addressing these challenges.
PMID- 25130029
TI - A retrospective study on the unseen epidemic of road traffic injuries and deaths
due to accidents in Mwanza City - Tanzania.
AB - BACKGROUNDS: Sixty percent of the global deaths and injuries occur in the
developing world and mostly are due to Road traffic accidents (RTAs. looking at
the etiological related factors which include, carelessness of the driver,
condition of the vehicle or motorcycle, poor condition of roads, risky behavior
of the driver, most of these factors can be prevented to some extent. This study
therefore, determined the pattern of cases and deaths due to traffic road
accidents in Mwanza City Tanzania. METHODS: In this retrospective study, records,
registers and case notes In the surgical ward and causality, medical records and
central police station from 2008 to 2011 were used. The study focused on the two
referral hospitals (Sekouture regional hospital and Bugando Medical Center).
RESULTS: There were 3450 cases due to accidents reported at both centers
(Sekouture regional hospital and Bugando Medical Center of which 3224 (93.4%) had
complete information for analysis.2225 (69%) were male and 999 (31%) were female,
and the most affected group were male. Among the RTAs2809 cases (87%) were due to
motor cycle accidents which were the leading cause of RTAs with case fatality
rate of 5% while motor vehicle has case fatality rate of 24% which is 5 times
that of motor cycle. CONCLUSION AND RECOMMENDATION: Among all RTAs the leading
cause of injuries is Motor cycle traffic accidents followed by motor vehicle.
RTAs are on increase particularly the motor cycle traffic accidents and has
claimed a good number of innocent people's lives however most of them are
preventable, therefore driving course to be introduced to motor cycle drivers
with emphasize on the road posters signal, rules and regular checkup of their
motor cycles especially commercial motor cycle.
PMID- 25130031
TI - [Dietary recommendations for chronic kidney disease, 2014].
PMID- 25130030
TI - [Classification of Diabetic Nephropathy 2014].
AB - The Committee on Diabetic Nephropathy revised the classification of diabetic
nephropathy in view of the current status of eGFR and CKD in Japan. To make
revisions for the classification of diabetic nephropathy 2014, the Committee
carefully evaluated the report of the Research Group on Diabetic Nephropathy,
Ministry of Health, Labour, and Welfare of Japan. The major revisions made were
as follows: 1. eGFR can be used for the evaluation of GFR; 2. In stage 3 (overt
nephropathy), A and B were combined; 3. Stage 4 (renal failure) was defined as
GFR less than 30 mL/min/1.73 m2, regardless of albuminuria; and 4. The importance
of differential diagnosis was stressed in all stages.
PMID- 25130032
TI - [A case of glomerulopathy associated with the vascular endothelial growth factor
inhibitor bevacizumab].
AB - The patient was a 73-year-old Japanese female diagnosed with stage IIIc primary
peritoneal cancer. After undergoing total hysterectomy and bilateral
oophorectomy, she received regimens consisting of paclitaxel (PTX) and
carboplatin (CBDCA). She subsequently developed recurrence four years after the
disease onset and was treated with PTX, CBDCA and the vascular endothelial growth
factor (VEGF) inhibitor bevacizumab (Bev). Although clinical remission was
maintained with the administration of Bev monotherapy every three weeks,
proteinuria was detected six months later, and gradually increased. The findings
of a renal biopsy showed diffuse wrinkling and double contouring of the
glomerular tufts under light microscopy, although no immune complex deposition
was observed on immunostaining. Additionally, electron microscopy showed
hypertrophy of glomerular endothelial cells and widening of the subendothelial
spaces. These histopathological findings were fully consistent with those of
reported patients treated with VEGF inhibitors. The proteinuria attenuated
following the initiation of treatment with losartan. Therefore, the
administration of renoprotective therapy contributed to the patient's ability to
continue the anticancer regimen with Bev in this case.
PMID- 25130033
TI - [A case of atypical hemolytic uremic syndrome successfully weaned from plasma
exchange by treatment with eculizumab].
AB - The patient was a 48-year-old man hospitalized for jaundice and anemia after a 6
day history of diarrhea. Examination demonstrated hemolytic anemia, renal
dysfunction, and thrombocytopenia. Typical hemolytic uremic syndrome (HUS) was
suspected based on the preceding colitis; however, plasma exchange (PE) was
performed because the possibility of atypical HUS (aHUS) could not be ignored,
given that the patient was an adult male. After 4 days of PE, his laboratory
results improved. Stool culture on admission yielded negative results for
Escherichia coli serotype O157 and ADAMTS13 activity. Antinuclear antibodies were
normal, and no other drugs or infections indicating HUS were detected. Four
months after onset, he suffered recurrence of aHUS after colitis. As a result,
aHUS was suspected and therefore, PE was performed on the day of hospitalization.
We diagnosed aHUS due to a result indicating complement dysregulation on
hemolytic assay testing, which detected a complement factor H abnormality. After
undergoing PE and maintaining a stable condition, the interval between PEs was
extended; however, on day 17 after the last PE, he suffered a recurrent aHUS
attack again. He could not be weaned from PE and started showing an allergic
reaction to PE treatment, thereby leading to a switch from PE to eculizumab.
Since switching to eculizumab treatment, the patient has not experienced another
aHUS attack and his condition remains stable.
PMID- 25130034
TI - [A case of thrombotic microangiopathy with glomerular subendothelial IgA
deposition due to bevacizumab].
AB - Bevacizumab, an inhibitor of vascular endothelial growth factor, is approved for
the treatment of various cancers, but the incidence of proteinuria as a side
effect has been reported to be 2-64%. We report a case of renal impairment due to
thrombotic microangiopathy (TMA) accompanied with glomerular subendothelial
deposition of IgA resulting from bevacizumab administration. A 57-year-old female
with advanced breast cancer, to whom bevacizumab had been administered from
October 2012, developed proteinuria and epithelial casts in her urine about a
month later. Serum creatinine remained at 0.7-0.8 mg/dL until June 2013, but
gradually increased to 1.3 mg/dL in September. She was referred to our hospital
because her renal function had not improved despite termination of bevacizumab,
and a renal biopsy was performed in October. At that time, the levels of
proteinuria, serum creatinine and serum IgA were high at 1.3 g/g x Cr, 1.6 mg/dL
and 430 mg/dL, respectively. Histological examinations showed prominent IgA
deposits in the subendothelial area and glomerular infiltration of CD68 positive
cells in addition to features of TMA, such as narrowed glomerular capillary
lumina and double contours of the basement membranes. In consideration of her
clinical history, a diagnosis of bevacizumab-induced TMA was made. Through follow
up care without readministration of bevacizumab, epithelial casts in her urine
disappeared, and proteinuria decreased to 0.62 g/g x Cr in November. Serum
creatinine remains high at around 1.3 mg/dL, but has not elevated further. Serum
IgA gradually decreased and reached 289 mg/dL in April 2014. TMA due to
bevacizumab described in several other reports was also accompanied by glomerular
IgA deposition, thus a differential diagnosis of IgA nephropathy is required. TMA
was recently added to a section of "significant adverse effects" in the package
insert of bevacizumab. Nephrologists should be fully aware of this drug-induced
nephropathy.
PMID- 25130035
TI - Foreword. Recent developments in the regulation of kinins.
PMID- 25130036
TI - Preface. Recent developments in the regulation of kinins.
PMID- 25130037
TI - Basic and clinical aspects of bradykinin receptor antagonists.
AB - Bradykinin and related kinins may act on two types of receptors designated as B1
and B2. It seems that the B2 receptors are most commonly found in various
vascular and non-vascular smooth muscles, whereas B1 receptors are formed in
vitro during trauma, and injury, and are found in bone tissues. These bradykinin
(BK) receptors are involved in the regulation of various physiological and
pathological processes. The mode of kinin actions are based upon the interactions
between the kinin and their specific receptors, which can lead to activation of
several second-messenger systems. Recently, numerous BK receptor antagonists have
been synthesized with prime aim to treat diseases caused by excessive kinin
production. These diseases are rheumatoid arthritis (RA), inflammatory diseases
of the bowel, asthma, rhinitis and sore throat, allergic reactions, pain,
inflammatory skin disorders, endotoxic and anaphylactic shock and coronary heart
diseases. On the other hand, BK receptor antagonists could be contraindicated in
hypertension, since these drugs may antagonize the antihypertensive therapy and/
or may trigger the hypertensive crisis. It is worth suggesting that the BK
receptor agonists might be useful antihypertensive drugs.
PMID- 25130038
TI - The kallikrein-kinin pathways in hypertension and diabetes.
AB - Cardiovascular diseases are the most common causes of mortality worldwide.
Hypertension and diabetes are the two major risk factors in the development of
cardiac hypertrophy, ischemic heart disease, and cardiac failure. In Kuwait, high
rate of prevalence of hypertension and diabetes has been documented. Previous
studies have indicated altered activities of the BK-generating components in
hypertension and diabetes. Bradykinin is pharmacologically active polypeptide
that can promote both cardiovascular and renal function, for example,
vasodilation, natriuresis, diuresis, and release of nitric oxide (NO). In
addition, B2 kinin receptors are present in the cardiac endothelial cells which
may enhance the biosynthesis and release of NO. It has been demonstrated that
reduced urinary (renal) kallikrein levels may be associated with the development
of high blood pressure in humans and spontaneously hypertensive and diabetic
rats. The BK may produce its pharmacological effects via NO and cyclic GMP
release. Furthermore, it is established that the BK has cardioprotective actions
in myocardial ischemia and can prevent left ventricular hypertrophy. Also,
transgenic mice carrying tissue kallikrein gene and overexpressing tissue
kallikrein had reduced blood pressure. NO synthase and renal tissue kallikrein
are both involved in blood pressure regulation. The ability of kallikrein gene
delivery and the use of kinin B2 receptor agonists to produce a wide spectrum of
beneficial effects make it a powerful candidate in treating hypertension,
cardiovascular, and renal diseases. Strategies that activate kinin receptors
might be applicable to the treatment of cardiovascular disease. Increased plasma
prekallikrein levels in diabetic patients may serve as an indicator of developing
hypertension and renal damage. Also high plasma and urine concentrations of
tissue kallikrein may cause higher glucose levels in the blood.
PMID- 25130039
TI - Tissue kallikrein-kinin therapy in hypertension and organ damage.
AB - Tissue kallikrein is a serine proteinase that cleaves low molecular weight
kininogen to produce kinin peptides, which in turn activate kinin receptors to
trigger multiple biological functions. In addition to its kinin-releasing
activity, tissue kallikrein directly interacts with the kinin B2 receptor,
protease-activated receptor-1, and gamma-epithelial Na channel. The tissue
kallikrein-kinin system (KKS) elicits a wide spectrum of biological activities,
including reducing hypertension, cardiac and renal damage, restenosis, ischemic
stroke, and skin wound injury. Both loss-of-function and gain-of-function studies
have shown that the KKS plays an important endogenous role in the protection
against health pathologies. Tissue kallikrein/kinin treatment attenuates
cardiovascular, renal, and brain injury by inhibiting oxidative stress,
apoptosis, inflammation, hypertrophy, and fibrosis and promoting angiogenesis and
neurogenesis. Approaches that augment tissue kallikrein-kinin activity might
provide an effective strategy for the treatment of hypertension and associated
organ damage.
PMID- 25130041
TI - The kallikrein-kinin system in diabetic retinopathy.
AB - Diabetic retinopathy (DR) is a major microvascular complication associated with
type 1 and type 2 diabetes mellitus, which can lead to visual impairment and
blindness. Current treatment strategies for DR are mostly limited to laser
therapies, steroids, and anti-VEGF agents, which are often associated with
unwanted side effects leading to further complications. Recent evidence suggests
that kinins play a primary role in the development of DR through enhanced
vascular permeability, leukocytes infiltration, and other inflammatory
mechanisms. These deleterious effects are mediated by kinin B1 and B2 receptors,
which are expressed in diabetic human and rodent retina. Importantly, kinin B1
receptor is virtually absent in sane tissue, yet it is induced and upregulated in
diabetic retina. These peptides belong to the kallikrein-kinin system (KKS),
which contains two separate and independent pathways of regulated serine
proteases, namely plasma kallikrein (PK) and tissue kallikrein (TK) that are
involved in the biosynthesis of bradykinin (BK) and kallidin (Lys-BK),
respectively. Hence, ocular inhibition of kallikreins or antagonism of kinin
receptors offers new therapeutic avenues in the treatment and management of DR.
Herein, we present an overview of the principal features and known inflammatory
mechanisms associated with DR along with the current therapeutic approaches and
put special emphasis on the KKS as a new and promising therapeutic target due to
its link with key pathways directly associated with the development of DR.
PMID- 25130040
TI - Renal (tissue) kallikrein-kinin system in the kidney and novel potential drugs
for salt-sensitive hypertension.
AB - A large variety of antihypertensive drugs, such as angiotensin converting enzyme
inhibitors, diuretics, and others, are prescribed to hypertensive patients, with
good control of the condition. In addition, all individuals are generally
believed to be salt sensitive and, thus, severe restriction of salt intake is
recommended to all. Nevertheless, the physiological defense mechanisms in the
kidney against excess salt intake have not been well clarified. The present
review article demonstrated that the renal (tissue) kallikrein-kinin system (KKS)
is ideally situated within the nephrons of the kidney, where it functions to
inhibit the reabsorption of NaCl through the activation of bradykinin (BK)-B2
receptors localized along the epithelial cells of the collecting ducts (CD).
Kinins generated in the CD are immediately inactivated by two kidney-specific
kinin-inactivating enzymes (kininases), carboxypeptidase Y-like exopeptidase
(CPY), and neutral endopeptidase (NEP). Our work demonstrated that ebelactone B
and poststatin are selective inhibitors of these kininases. The reduced secretion
of the urinary kallikrein is linked to the development of salt-sensitive
hypertension, whereas potassium ions and ATP-sensitive potassium channel blockers
ameliorate salt-sensitive hypertension by accelerating the release of renal
kallikrein. On the other hand, ebelactone B and poststatin prolong the life of
kinins in the CD after excess salt intake, thereby leading to the augmentation of
natriuresis and diuresis, and the ensuing suppression of salt-sensitive
hypertension. In conclusion, accelerators of the renal kallikrein release and
selective renal kininase inhibitors are both novel types of antihypertensive
agents that may be useful for treatment of salt-sensitive hypertension.
PMID- 25130042
TI - Genetic manipulation and genetic variation of the kallikrein-kinin system: impact
on cardiovascular and renal diseases.
AB - Genetic manipulation of the kallikrein-kinin system (KKS) in mice, with either
gain or loss of function, and study of human genetic variability in KKS
components which has been well documented at the phenotypic and genomic level,
have allowed recognizing the physiological role of KKS in health and in disease.
This role has been especially documented in the cardiovascular system and the
kidney. Kinins are produced at slow rate in most organs in resting condition
and/or inactivated quickly. Yet the KKS is involved in arterial function and in
renal tubular function. In several pathological situations, kinin production
increases, kinin receptor synthesis is upregulated, and kinins play an important
role, whether beneficial or detrimental, in disease outcome. In the setting of
ischemic, diabetic or hemodynamic aggression, kinin release by tissue kallikrein
protects against organ damage, through B2 and/or B1 bradykinin receptor
activation, depending on organ and disease. This has been well documented for the
ischemic or diabetic heart, kidney and skeletal muscle, where KKS activity
reduces oxidative stress, limits necrosis or fibrosis and promotes angiogenesis.
On the other hand, in some pathological situations where plasma prekallikrein is
inappropriately activated, excess kinin release in local or systemic circulation
is detrimental, through oedema or hypotension. Putative therapeutic application
of these clinical and experimental findings through current pharmacological
development is discussed in the chapter.
PMID- 25130043
TI - Increased transfusion-free survival following auxiliary pig liver
xenotransplantation.
AB - BACKGROUND: Pig to baboon liver xenotransplantation typically results in severe
thrombocytopenia and coagulation disturbances, culminating in death from
hemorrhage within 9 days, in spite of continuous transfusions. We studied the
contribution of anticoagulant production and clotting pathway deficiencies to
fatal bleeding in baboon recipients of porcine livers. METHODS: By transplanting
liver xenografts from alpha1,3-galactosyltransferase gene-knockout (GalT-KO)
miniature swine donors into baboons as auxiliary organs, leaving the native liver
in place, we provided the full spectrum of primate clotting factors and allowed
in vivo mixing of porcine and primate coagulation systems. RESULTS: Recipients of
auxiliary liver xenografts develop severe thrombocytopenia, comparable to
recipients of conventional orthotopic liver xenografts and consistent with
hepatic xenograft sequestration. However, baboons with both pig and native livers
do not exhibit clinical signs of bleeding and maintain stable blood counts
without transfusion for up to 8 consecutive days post-transplantation. Instead,
recipients of auxiliary liver xenografts undergo graft failure or die of sepsis,
associated with thrombotic microangiopathy in the xenograft, but not the native
liver. CONCLUSION: Our data indicate that massive hemorrhage in the setting of
liver xenotransplantation might be avoided by supplementation with primate
clotting components. However, coagulation competent hepatic xenograft recipients
may be predisposed to graft loss related to small vessel thrombosis and ischemic
necrosis.
PMID- 25130044
TI - Altered expression of 3beta-HSD, CYP17 and 17beta-HSD in the foetal porcine
gonads in response to anti-androgen flutamide exposure.
AB - We investigated whether the limited access to androgens during late prenatal
period alters expression of steroidogenic enzymes involved in androgen
production: 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase (3beta
HSD), cytochrome P450 17alpha-hydroxylase/17,20-lyase (CYP17) and 17beta
hydroxysteroid dehydrogenase type 1 (17beta-HSD1) or type 3 (17beta-HSD3) in the
foetal porcine gonads. Pregnant gilts were injected with anti-androgen flutamide
(for seven days, 50 mg/day/kg bw) or corn oil (control) starting at 83 (GD90) or
101 (GD108) gestational day. To assess 3beta-HSD, CYP17 and 17beta-HSD1 or 17beta
HSD3 expression, real-time PCR and immunohistochemistry were performed. In testes
from flutamide-treated foetuses, increased 3beta-HSD and CYP17 mRNA expression
was observed in the GD90 group, while decreased 3beta-HSD and 17beta-HSD3 mRNA
expression and increased CYP17 mRNA expression were found in the GD108 group.
CYP17 and 17beta-HSD3 were localized in Leydig cells. Following flutamide
administration, the intensity of CYP17 immunostaining was higher in both treated
groups, while 17beta-HSD3 intensity was lower in the GD108 group. In ovaries from
flutamide-treated foetuses in the GD90 group, mRNA level for 3beta-HSD was
elevated, but it was diminished for CYP17 and 17beta-HSD1. In the GD108 group,
flutamide treatment led to lower mRNA level for 3beta-HSD but higher for CYP17.
3beta-HSD was found in granulosa cells, while CYP17 was localized within egg
nests and oocytes of forming follicles. Following flutamide treatment, the
intensity of 3beta-HSD and CYP17 immunostaining was higher in the GD90 and GD108
groups, respectively. Immunohistochemical staining for 3beta-HSD was restricted
to the ovary. Concluding, diminished androgen action in the porcine foetal gonads
during late gestation induces changes in steroidogenic enzymes expression, which
may led to changes in gonadal function. However, it seems that androgens exert
diverse biological effects depending on the gestational period.
PMID- 25130045
TI - Comparison of the results of intradermal test reactivity and serum allergen
specific IgE measurement for Malassezia pachydermatis in atopic dogs.
AB - BACKGROUND: Malassezia pachydermatis is part of the normal flora of canine skin.
Malassezia hypersensitivity is recognized as a trigger for clinical signs of
atopic dermatitis (AD) in some dogs. Determinations of Malassezia
hypersensitivity are often made with intradermal testing (IDT), which may have
limited availability in a first-opinion veterinary practice.
HYPOTHESIS/OBJECTIVES: The purpose of this study was to compare immediate IDT
reactivity to M. pachydermatis with results of an enzyme-linked immunosorbent
assay (ELISA) designed to detect anti-Malassezia IgE. ANIMALS: Eighty-four dogs
with a clinical diagnosis of AD. METHODS: Multi-allergen IDT was performed on all
dogs. Serum testing for allergen-specific IgE against a panel of common
environmental allergens and M. pachydermatis was performed by ELISA using the
FcepsilonRIalpha receptor fragment as a detection reagent, with results reported
as adjusted optical density (OD). A receiver operating characteristic (ROC) curve
was used to analyse the results of the two tests. RESULTS: The median adjusted OD
of the anti-Malassezia IgE ELISA for dogs reactive and nonreactive to M.
pachydermatis on IDT was 0.137 and 0.024, respectively. Analysis of the ROC curve
suggested a cut-off point for the anti-Malassezia ELISA that yielded a
sensitivity of 77.0% and a specificity of 89% relative to IDT results.
CONCLUSIONS AND CLINICAL IMPORTANCE: Substantial agreement was demonstrated
between IDT reactivity and anti-Malassezia IgE as detected by the
FcepsilonRIalpha receptor reagent. Although correlation with a clinical diagnosis
of Malassezia dermatitis was not attempted in this study, the results indicate
that the ELISA may be used to demonstrate the presence of immediate-type
Malassezia hypersensitivity in dogs with AD.
PMID- 25130046
TI - Practitioner Review: Diagnosing childhood resilience--a systemic approach to the
diagnosis of adaptation in adverse social and physical ecologies.
AB - BACKGROUND: With growing interest in resilience among mental health care
providers globally, there is a need for a simple way to consider the complex
interactions that predict adaptive coping when there is exposure to high levels
of adversity such as family violence, mental illness of a child or caregiver,
natural disasters, social marginalization, or political conflict. METHODS: This
article presents diagnostic criteria for assessing childhood resilience in a way
that is sensitive to the systemic factors that influence a child's wellbeing. The
most important characteristics of children who cope well under adversity and
avoid problems like depression, PTSD, and delinquency are highlighted. RESULTS: A
multidimensional assessment of resilience is presented that examines, first, the
severity, chronicity, ecological level, children's attributions of causality, and
cultural and contextual relevance of experiences of adversity. Second, promotive
and protective factors related to resilience are assessed with sensitivity to the
differential impact these have on outcomes depending on a child's level of
exposure to adversity. These factors include individual qualities like
temperament, personality, and cognitions, as well as contextual dimensions of
positive functioning related to the available and accessibility of resources,
their strategic use, positive reinforcement by a child's significant others, and
the adaptive capacity of the environment itself. Third, an assessment of
resilience includes temporal and cultural factors that increase or decrease the
influence of protective factors. A decision tree for the diagnosis of resilience
is presented, followed by a case study and diagnosis of a 15-year-old boy who
required treatment for a number of mental health challenges. CONCLUSIONS: The
diagnostic criteria for assessing resilience and its application to clinical
practice demonstrate the potential usefulness of a systemic approach to
understanding resilience among child populations.
PMID- 25130047
TI - Management of children with possible appendicitis: a survey of emergency
physicians in Australia and New Zealand.
AB - OBJECTIVES: To describe current practice in managing children with possible acute
appendicitis in EDs in Australia and New Zealand as the basis for a clinical
practice guideline (CPG). METHODS: An anonymous survey was distributed to
consultant emergency physicians working at PREDICT (Paediatric Research in
Emergency Departments International Collaborative) sites in Australia and New
Zealand in April 2013. A second, site-based survey was distributed to the PREDICT
representatives at each of the 13 sites. RESULTS: The response rate was 100%
(13/13) for the site-based survey and 82% (145/176) for the physician survey.
Most respondents agreed that right lower quadrant (RLQ) tenderness (94%),
anorexia (92%), migration of abdominal pain to the RLQ (86%), rebound tenderness
in the RLQ (60%) and RLQ tenderness produced on coughing, hopping or percussion
(63%) were valuable symptoms and signs in diagnosing appendicitis. The responses
regarding nausea and vomiting and fever were less consistent. Less than 50%
regarded blood tests (C-reactive protein, white cell count) as relevant for the
diagnosis of appendicitis. Most physicians (61%) agreed there was a role for a
validated CPG for possible appendicitis in children, although only 3/13 sites
reported use of such a CPG. CONCLUSIONS: This survey of senior emergency
physicians across Australia and New Zealand demonstrated congruence in several
clinical markers and disagreements in others in the approach to diagnosing
children with possible appendicitis. Whereas emergency physicians would like a
validated CPG, this survey has highlighted some critical issues. Particularly,
the low regard for blood tests, integral to published diagnostic scoring systems,
will be a challenge for the development and introduction of such a CPG in
Australia and New Zealand.
PMID- 25130048
TI - The effect of trait type and strength of selection on heritability and
evolvability in an island bird population.
AB - The heritability (h(2) ) of fitness traits is often low. Although this has been
attributed to directional selection having eroded genetic variation in direct
proportion to the strength of selection, heritability does not necessarily
reflect a trait's additive genetic variance and evolutionary potential
("evolvability"). Recent studies suggest that the low h(2) of fitness traits in
wild populations is caused not by a paucity of additive genetic variance (VA )
but by greater environmental or nonadditive genetic variance (VR ). We examined
the relationship between h(2) and variance-standardized selection intensities (i
or betasigma ), and between evolvability (IA :VA divided by squared phenotypic
trait mean) and mean-standardized selection gradients (betaMU ). Using 24 years
of data from an island population of Savannah sparrows, we show that, across
diverse traits, h(2) declines with the strength of selection, whereas IA and IR
(VR divided by squared trait mean) are independent of the strength of selection.
Within trait types (morphological, reproductive, life-history), h(2) , IA , and
IR are all independent of the strength of selection. This indicates that certain
traits have low heritability because of increased residual variance due to the
age at which they are expressed or the multiple factors influencing their
expression, rather than their association with fitness.
PMID- 25130049
TI - Evidence-based guidelines for laboratory screening for infectious diseases before
initiation of systemic immunosuppressive agents in patients with autoimmune
bullous dermatoses.
AB - Autoimmune bullous dermatoses (ABD) compromise the skin's innate barrier function
for preventing infection. Treating patients with ABD frequently requires systemic
immunosuppressive therapy, often with multiple agents. Currently, no pretreatment
infection testing guidelines are available for clinicians caring for patients
with ABD. We performed a systematic literature review in other medical
disciplines that use similar iatrogenic immunosuppressive medications to treat
various diseases and conditions and developed infection-testing recommendations
for patients with ABD before initiating immunosuppressive therapy. Assessing
individual patient risk factors for latent infection and preventable communicable
diseases can direct testing for select infections before starting
immunosuppressive therapy. Testing patients for hepatitis B virus, hepatitis C
virus, and Mycobacterium tuberculosis infection is recommended before initiating
rituximab treatment.
PMID- 25130050
TI - Prevalence and risk factors for isolation of methicillin-resistant Staphylococcus
in dogs with keratitis.
AB - OBJECTIVE: To determine the prevalence of, and risk factors for, methicillin
resistant Staphylococcus (MRS) isolation in dogs with naturally acquired
bacterial keratitis. PROCEDURES: All Staphylococcus spp. isolated from corneal
samples of dogs with keratitis during a 2-year period were evaluated for
methicillin resistance by bacteriologic methods. Each MRS isolate was subjected
to in vitro susceptibility testing for systemic and ocular antimicrobials. Nasal
swabs for culture were collected from all dogs with MRS corneal isolation to
evaluate for nasal carrier status. Potential risk factors for MRS isolation were
investigated by medical record review and administration of an epidemiological
survey to dog owners. Collected information characterizing animal, client, and
environmental variables was analyzed for association with MRS isolation. RESULTS:
Seventy-one Staphylococcus spp. were isolated from seventy individual dogs with
keratitis during the study period. Seventeen of the Staphylococcus isolates
(23.9%) were methicillin resistant. The MRS isolates included Staphylococcus
epidermidis (n = 10), Staphylococcus pseudintermedius (n = 6), and Staphylococcus
aureus (n = 1). The MRS corneal isolates displayed extensive antimicrobial
resistance. Four dogs (23.5%) with MRS corneal isolates had positive nasal
cultures for MRS. Client occupation was significantly (P = 0.01) associated with
MRS isolation, and dogs belonging to owners employed in veterinary or human
healthcare fields were four times more likely to have MRS keratitis than dogs
owned by clients with different professions. There were no significant
associations between the other evaluated animal, client, and environmental
factors. CONCLUSIONS: Methicillin resistance is relatively common in
Staphylococcus isolates from dogs with corneal infections, particularly among
dogs belonging to healthcare workers.
PMID- 25130051
TI - Portal blood - a new source of dendritic cells for pancreatic cancer vaccine.
AB - INTRODUCTION: Cohort study evaluated dendritic cells (DCs) subsets in portal and
peripheral blood of patients with pancreatic cancer (PC) and chronic pancreatitis
(CHP). MATERIAL AND METHODS: Myeloid type 1 (mDCs1) and 2 (mDCs2), plasmocytoid
(pDCs) and SLAN + DCs were assessed in PC (n = 20) and CHP (n = 6) patients.
RESULTS: Percentage of mDCs1 was significantly lower in PC patients when compared
to CHP (0.48 +/- 0.26 vs 0.76 +/- 0.3; p = 0.038) only in portal, but not
peripheral blood. DISCUSSION: Further studies to assess the functional properties
of portal blood DCs and their applicability in anticancer vaccination are needed.
PMID- 25130053
TI - Upper limb joint kinetics of three sitting pivot wheelchair transfer techniques
in individuals with spinal cord injury.
AB - STUDY DESIGN: Repeated measures design. OBJECTIVE: This study compared the upper
extremity (UE) joint kinetics between three transfer techniques. SETTING:
Research laboratory. METHODS: Twenty individuals with spinal cord injury
performed three transfer techniques from their wheelchair to a level tub bench.
Two of the techniques involved a head-hips method with leading hand position
close (HH-I) and far (HH-A) from the body, and the third technique with the trunk
upright (TU) and hand far from body. Motion analysis equipment recorded upper
body movements and force sensors recorded their hand and feet reaction forces
during the transfers. RESULTS: Several significant differences were found between
HH-A and HH-I and TU and HH-I transfers indicating that hand placement was a key
factor influencing the UE joint kinetics. Peak resultant hand, elbow, and
shoulder joint forces were significantly higher for the HH-A and TU techniques at
the trailing arm (P < 0.036) and lower at the leading arm (P < 0.021), compared
to the HH-I technique. CONCLUSION: Always trailing with the same arm if using HH
A or TU could predispose that arm to overuse related pain and injuries. Technique
training should focus on initial hand placement close to the body followed by the
amount of trunk flexion needed to facilitate movement.
PMID- 25130052
TI - Pharmacodynamic effects of oral oxymorphone: abuse liability, analgesic profile
and direct physiologic effects in humans.
AB - Oxymorphone is a semisynthetic MU-opioid agonist, marketed as a prescription
analgesic purported to be twice as potent as oxycodone for pain relief. Oral
formulations of oxymorphone were reintroduced in the United States in 2006 and
reports of abuse ensued; however, there are limited data available on its
pharmacodynamic effects. The current study aimed to examine the direct
physiologic effects, relative abuse liability, analgesic profile and overall
pharmacodynamic potency of oxymorphone in comparison with identical doses of
oxycodone. Healthy, non-dependent opioid abusers (n = 9) were enrolled in this
within-subject, double-blind, placebo-controlled, 3-week inpatient study. Seven
experimental sessions (6.5 hours) were conducted, during which an oral dose of
immediate-release formulations of oxymorphone (10, 20 and 40 mg), oxycodone (10,
20 and 40 mg) or placebo was administered. An array of physiologic, abuse
liability and experimental pain measures was collected. At identical doses,
oxymorphone produced approximately twofold less potent effects on miosis,
compared with oxycodone. Oxymorphone also produced lesser magnitude effects on
measures of respiratory depression, two experimental pain models and observer
rated agonist effects. However, 40 mg of oxymorphone was similar to 40 mg of
oxycodone on several abuse-related subjective ratings. Formal relative potency
analyses were largely invalid because of the substantially greater effects of
oxycodone. Overall, oxymorphone is less potent on most pharmacodynamic measures,
although at higher doses, its abuse liability is similar to oxycodone. These data
suggest that the published clinical equianalgesic estimates may not be consistent
with the observed direct physiologic effects of opioids, results of experimental
pain models or abuse liability measures, as assessed in the human laboratory.
PMID- 25130056
TI - Necessary stem cell transplantation using myeloablative therapy for
myelodysplastic syndrome with progression of genotypic abnormalities and TP53
dysfunction in a young adult.
AB - A 14-yr-old male was admitted to our hospital with MDS and the chromosomal
abnormality 45,XY,der(5;17)(p10;q10). He rapidly developed karyotype
abnormalities, accompanied by the loss of tumor suppressor gene TP53 function. He
suffered an early relapse after reduced-intensity-conditioning SCT and ultimately
required myeloablative therapy before a second SCT. We consider that the analysis
of TP53 mutations is essential when planning the treatment of patients with MDS.
PMID- 25130054
TI - Assessment of respiration-induced displacement of canine abdominal organs in
dorsal and ventral recumbency using multislice computed tomography.
AB - Respiratory-induced organ displacement during image acquisition can produce
motion artifacts and variation in spatial localization of an organ in diagnostic
computed tomography (CT) examinations. The purpose of this prospective study was
to quantify respiratory-induced abdominal organ displacement in dorsal and
ventral recumbency using five normal dogs. All dogs underwent CT examinations
using 64 multidetector row CT (64-MDCT). A "3-dimensional (3D) apneic CT exam" of
the abdomen was acquired followed by a "4-dimensional (4D) ventilated CT exam."
The liver, pancreas, both kidneys, both medial iliac lymph nodes, and urinary
bladder were delineated on the 3D-apneic examination and the organ outlines were
compared to the maximum alteration in organ position in the 4D-ventilated
examination. Displacement was measured in dorsal-to-ventral (DV), right-to-left
(RL), and cranial-to-caudal (CC) directions. Respiratory-induced displacement of
canine abdominal organs was not predictable and showed large variability in the
three directions evaluated. For most canine abdominal organs, dorsal recumbency
provided overall the least amount of displacement among all directions evaluated
except for liver and urinary bladder. For liver, a large variability was found
for all directions and a statistically significant difference was found only in
the RL direction with ventral recumbency exhibiting less displacement (P =
0.0099). For the urinary bladder, ventral recumbency also provided less
displacement but this was statistically significant only in the RL direction (P <
0.0001). Findings from this study indicated that dorsal recumbency may be
preferred for minimizing respiratory motion artifacts in whole abdomen studies,
but ventral recumbency may be preferred for liver and urinary bladder studies
when respiration cannot be controlled.
PMID- 25130057
TI - Targeted proteomics analysis of protein degradation in plant signaling on an LTQ
Orbitrap mass spectrometer.
AB - Targeted proteomics has become increasingly popular recently because of its
ability to precisely quantify selected proteins in complex cellular backgrounds.
Here, we demonstrated the utility of an LTQ-Orbitrap Velos Pro mass spectrometer
in targeted parallel reaction monitoring (PRM) despite its unconventional dual
ion trap configuration. We evaluated absolute specificity (>99%) and sensitivity
(100 amol on column in 1 MUg of total cellular extract) using full and mass range
scans as survey scans together with data-dependent (DDA) and targeted MS/MS
acquisition. The instrument duty cycle was a critical parameter limiting
sensitivity, necessitating peptide retention time scheduling. We assessed
synthetic peptide and recombinant peptide standards to predict or experimentally
determine target peptide retention times. We applied optimized PRM to protein
degradation in signaling regulation, an area that is receiving increased
attention in plant physiology. We quantified relative abundance of selected
proteins in plants that are mutant for enzymatic components of the N-end rule
degradation (NERD) pathway such as the two tRNA-arginyl-transferases ATE1 and
ATE2 and the two E3 ubiquitin ligases PROTEOLYSIS1 and 6. We found a number of
upregulated proteins, which might represent degradation targets. We also targeted
FLAGELLIN SENSITIVE2 (FLS2), a pattern recognition receptor responsible for
pathogen sensing, in ubiquitin ligase mutants to assay the attenuation of plant
immunity by degradation of the receptor.
PMID- 25130058
TI - Human tyrosinase is able to oxidize both enantiomers of rhododendrol.
AB - Racemic RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol, RD) was used as a topical
skin-whitening agent until it was recently reported to induce leukoderma. We then
showed that oxidation of RD with mushroom tyrosinase rapidly produces RD-quinone,
which is quickly converted to RD-cyclic quinone and RD-hydroxy-p-quinone. In this
study, we examined whether either or both of the enantiomers of RD can be
oxidized by human tyrosinase. Using a chiral HPLC column, racemic RD was resolved
optically to R(-)-RD and S(+)-RD enantiomers. In the presence of a catalytic
amount of l-dopa, human tyrosinase, which can oxidize l-tyrosine but not d
tyrosine, was found to oxidize both R(-)- and S(+)-RD to give RD-catechol and its
oxidation products. S(+)-RD was more effectively oxidized than l-tyrosine, while
R(-)-RD was less effective. These results support the notion that the melanocyte
toxicity of RD depends on its tyrosinase-catalyzed conversion to toxic quinones
and the concomitant production of reactive oxygen species.
PMID- 25130059
TI - Drowned, buried and carried away: effects of plant traits on the distribution of
native and alien species in riparian ecosystems.
AB - Riparian vegetation is exposed to stress from inundation and hydraulic
disturbance, and is often rich in native and alien plant species. We describe 35
traits that enable plants to cope with riparian conditions. These include traits
for tolerating or avoiding anoxia and enabling underwater photosynthesis, traits
that confer resistance and resilience to hydraulic disturbance, and attributes
that facilitate dispersal, such as floating propagules. This diversity of life
history strategies illustrates that there are many ways of sustaining life in
riparian zones, which helps to explain high riparian biodiversity. Using
community assembly theory, we examine how adaptations to inundation, disturbance
and dispersal shape plant community composition along key environmental
gradients, and how human actions have modified communities. Dispersal-related
processes seem to explain many patterns, highlighting the influence of regional
processes on local species assemblages. Using alien plant invasions like an
(uncontrolled) experiment in community assembly, we use an Australian and a
global dataset to examine possible causes of high degrees of riparian invasion.
We found that high proportions of alien species in the regional species pools
have invaded riparian zones, despite not being riparian specialists, and that
riparian invaders disperse in more ways, including by water and humans, than
species invading other ecosystems.
PMID- 25130060
TI - Intraoperative changes in blood pressure, heart rate, plasma vasopressin, and
urinary noradrenalin during elective ovariohysterectomy in dogs: repeatability at
removal of the 1st and 2nd ovary.
AB - OBJECTIVE: To investigate the physiologic reactions after removal of 1st ovary
and whether this is repeated during removal of the 2nd ovary in elective
ovariohysterectomy. STUDY DESIGN: Prospective study. ANIMALS: Dogs (n = 10).
METHODS: Dogs were premedicated with acepromazine, carprofen, and methadone and
anesthetized with propofol and isoflurane. Blood pressure, heart rate, and end
tidal isoflurane concentration were measured every minute. The effects of various
events during surgery on physiologic variables were analyzed using mixed linear
models. Blood and urine samples were collected before anesthesia, before
incision, before and after removal of ovaries with a 15 minute pause between
ovary removal, and after abdominal closure. Plasma vasopressin and urinary
noradrenalin and creatinine concentrations were analyzed. RESULTS: The magnitude
of blood pressure increase at removal of the 1st ovary was greater than for the
2nd ovary because of an elevation in baseline. Similarly, the heart rate
increased at the removal of the 1st ovary but not at removal of the 2nd ovary.
Plasma vasopressin concentration increased at removal of both ovaries. Urinary
noradrenalin/creatinine ratio increased at anesthesia, removal of both ovaries,
and was elevated at closure of the abdomen. End-tidal isoflurane concentration
did not change. Blood pressure and vasopressin concentrations changed in parallel
using z-scores for comparison. CONCLUSIONS: Peak values for blood pressure, heart
rate, plasma vasopressin concentration, and urinary noradrenalin/creatinine ratio
did not differ between removals of the ovaries. Relative changes differed between
repeated noxious stimuli, which should be considered in evaluation of methods at
ovary removal.
PMID- 25130062
TI - Lithium for bipolar disorder: a review of the recent literature.
AB - Lithium is a commonly prescribed treatment for bipolar disorder. Many early
studies on which its use has been historically based no longer meet current
research standards. A large number of studies with more modern designs have been
recently published warranting a review. New research adds to the evidence for
lithium's efficacy in mania and maintenance. There is also additional evidence,
albeit less robust, to support its benefit in bipolar depression and mixed
episodes. Meta-analyses of mainly observational data have found reduced suicidal
behavior in bipolar patients taking lithium. Careful monitoring and prescribing
can reduce the risk of adverse effects.
PMID- 25130061
TI - Effects of lifestyle modification and metformin on irisin and FGF21 among HIV
infected subjects with the metabolic syndrome.
AB - OBJECTIVE: Few studies have investigated irisin and FGF21 to elucidate the role
of these hormones to regulate 'beiging' in HIV-infected patients. DESIGN: Fifty
HIV-infected subjects with the metabolic syndrome were previously recruited and
randomized to receive lifestyle modification (LSM) and/or metformin over 12
months. In the current study, we assessed FGF21 and irisin at baseline and after
intervention. In addition, we assessed circulating FGF21 and irisin in
relationship to brown adipose tissue (BAT) gene expression in dorsocervical
subcutaneous fat biopsies from 13 HIV-infected subjects. RESULTS: At baseline,
prior to intervention, HIV-infected subjects demonstrated increased log FGF21
(2.13 +/- 0.06 vs 1.98 +/- 0.05 pg/ml, P = 0.05) and log irisin (0.33 +/- 0.02 vs
0.17 +/- 0.04 MUg/ml, P = 0.003) compared with healthy controls well matched
based on waist circumference. After 12 months, HIV-infected subjects randomized
to LSM demonstrated a relative reduction in FGF21 compared with those not
randomized to LSM (-10 [-35,22] vs 40 [0,94] %change, P = 0.01). Changes in FGF21
were inversely associated with improved parameters of energy homoeostasis,
including increased REE (rho = -0.34, P = 0.046) and max VO2 (rho = -0.38, P =
0.02), and reduced RQ (rho = 0.40, P = 0.02) among all HIV-infected subjects.
Increased UCP-1 (r = 0.75, P = 0.003), DIO2 (r = 0.58, P = 0.04) and CideA (r =
0.73, P = 0.01) gene expression in dorsocervical fat was significantly associated
with FGF21 in HIV-infected subjects. CONCLUSION: HIV-infected subjects with
metabolic complications demonstrate increases in FGF21 in relationship to BAT
gene expression. Relative reductions in FGF21 in those receiving long-term LSM
relate to overall improvements in energy expenditure parameters. In contrast,
irisin levels are elevated in HIV-infected subjects, but are not influenced by
LSM nor associated with BAT gene expression.
PMID- 25130063
TI - Acylation of ghrelin is increased in heart failure and decreases post heart
transplantation.
AB - OBJECTIVES: Ghrelin is an anabolic hormone that is elevated in heart failure
(HF), with resistance to its anabolic effects. This resolves after heart
transplantation (HTx). Ghrelin exists in acylated and des-acyl forms, with the
acylated form being primarily responsible for endocrine actions. We tested the
hypothesis that ghrelin derangements in HF are due to inadequate acylation and
that this resolves post transplantation. DESIGN: Plasma levels of des-acyl and
acylated ghrelin and acylated/total ratios were assessed in HF (n = 20), post-HTx
(n = 35), and healthy controls (n = 4), and correlated with each other and with
clinical parameters. RESULTS: Median (interquartile range) of des-acyl ghrelin
level, was 167 (121-195) pg/ml in HF versus 149 (130-223) pg/ml in post-HTx, p =
NS. Acylated ghrelin level was 76 (51-99) pg/ml versus 13 (0-30) pg/ml, p <
0.001. Acylated/total ratios were 0.33 (0.20-0.47) versus 0.08 (0-0.13), p <
0.001. The correlation between acylated and total ghrelin levels was greater in
HF than that in HTx. Acyl ghrelin correlated inversely with body mass index in
HF, but not in HTx. CONCLUSION: Acylated ghrelin and the acylated/total ratio
were dramatically higher in HF compared with those in HTx. Acylation rather than
secretion of ghrelin is upregulated in HF and the resistance to ghrelin's
anabolic and appetite-stimulating effects is not at the level of acylation, but
downstream at the ghrelin-receptor level.
PMID- 25130064
TI - Cost analysis of the development and implementation of a spatial decision support
system for malaria elimination in Solomon Islands.
AB - BACKGROUND: The goal of malaria elimination faces numerous challenges. New tools
are required to support the scale up of interventions and improve national
malaria programme capacity to conduct detailed surveillance. This study
investigates the cost factors influencing the development and implementation of a
spatial decision support system (SDSS) for malaria elimination in the two
elimination provinces of Isabel and Temotu, Solomon Islands. METHOD: Financial
and economic costs to develop and implement a SDSS were estimated using the
Solomon Islands programme's financial records. Using an ingredients approach,
verified by stakeholders and operational reports, total costs for each province
were quantified. A budget impact sensitivity analysis was conducted to
investigate the influence of variations in standard budgetary components on the
costs and to identify potential cost savings. RESULTS: A total investment of US$
96,046 (2012 constant dollars) was required to develop and implement the SDSS in
two provinces (Temotu Province US$ 49,806 and Isabel Province US$ 46,240). The
single largest expense category was for computerized equipment totalling
approximately US$ 30,085. Geographical reconnaissance was the most expensive
phase of development and implementation, accounting for approximately 62% of
total costs. Sensitivity analysis identified different cost factors between the
provinces. Reduced equipment costs would deliver a budget saving of approximately
10% in Isabel Province. Combined travel costs represented the greatest influence
on the total budget in the more remote Temotu Province. CONCLUSION: This study
provides the first cost analysis of an operational surveillance tool used
specifically for malaria elimination in the South-West Pacific. It is
demonstrated that the costs of such a decision support system are driven by
specialized equipment and travel expenses. Such factors should be closely
scrutinized in future programme budgets to ensure maximum efficiencies are gained
and available resources are allocated effectively.
PMID- 25130065
TI - The mental health of unaccompanied refugee minors on arrival in the host country.
AB - Despite increasing numbers of unaccompanied refugee minors (UM) in Europe and
heightened concerns for this group, research on their mental health has seldom
included the factor "time since arrival." As a result, our knowledge of the
mental health statuses of UM at specific points in time and over periods in their
resettlement trajectories in European host countries is limited. This study
therefore examined the mental health of UM shortly after their arrival in Norway
(n = 204) and Belgium (n = 103) through the use of self-report questionnaires
(HSCL-37A, SLE, RATS, HTQ). High prevalence scores of anxiety, depression and
posttraumatic stress disorder (PTSD) symptoms were found. In addition, particular
associations were found with the number of traumatic events the UM reported. The
results indicate that all UM have high support needs on arrival in the host
country. Longitudinal studies following up patterns of continuity and change in
their mental health during their trajectories in the host country are necessary.
PMID- 25130066
TI - Study on accommodation by autorefraction and dynamic refraction in children.
AB - PURPOSE: Childhood accommodation interferes with accurate diagnosis of the latent
refractive errors. Dynamic retinoscopy offers accurate measurements of
accommodative response, while an autorefractometer can predict the accommodative
system activation in children. A correlation of the accommodative effort with the
dynamic refraction has been investigated in emmetropic children, before and after
cycloplegia. METHODS: A prospective clinical study of accommodative effort in 149
emmetropic children, in the age group 3-16 years, has been conducted using TOPCON
AR RM-8000B autorefractor. Dynamic refraction was performed by monocular
estimation method before and after cycloplegia, using the retinoscope mirror
light as target. Retinoscopic reflex produced 'with the motion' was corrected
with positive spherical lenses, and that 'against the motion' was corrected with
negative spherical lenses, to achieve neutralization. RESULTS: Mean accommodative
effort measured for 149 children included in the study was -0.63+/-0.69D and
dynamic refraction was -0.07+/-0.44D before cycloplegia, while the mean was+0.52D
after cycloplegia, irrespective of the method used. Autorefractor measured -0.17D
of accommodative effort per unit change in dynamic refraction before cycloplegia
and +0.90D after cycloplegia. CONCLUSIONS: The performance of TOPCON AR RM-8000B
autorefractor was comparable to dynamic retinoscopy. Presence of many children,
and in turn, large number of accommodative response data in 11-13 and 14-15 years
group is probably linked to prolonged reading/writing. The accuracy and the
agreement of the actual accommodative measurements revealed after cycloplegia.
PMID- 25130067
TI - Bowman strip complications during routine LASIK: Two cases demonstrating the
clinical advantage of using Mitomicyn C in such cases.
PMID- 25130068
TI - Does organizational justice predict empowerment? Nurses assess their work
environment.
AB - PURPOSE: The purpose of the study was to explore how nurses assess their
empowerment and clarify organizational justice compared to other work-related
factors. In addition, we examined the major variables pertinent to empowerment.
DESIGN: Cross-sectional survey data were used. METHODS: A total of 2,152 nurses
returned the completed questionnaire. The instruments consisted of nurse
empowerment, organizational justice, job control, and possibilities for
developing work. The data analysis was based on descriptive statistics and
further statistical tests. FINDINGS: Organizational justice and empowerment had a
clear correlation. Job control, possibilities for developing work and
organizational justice were statistically significant predictors of nurse
empowerment. CONCLUSIONS: Organizational justice and the possibility to use one's
individual skills at work are significant factors in staff activity and its
development in nursing. They increase the level of empowerment and commitment as
well as motivation to work. CLINICAL RELEVANCE: The results of this study confirm
that nurses regard organizational justice as highly important. We can facilitate
both work-related empowerment and organizational justice by creating and
maintaining a culture of fairness and justice. Employees should be heard and
involved more in the planning and decision making of work.
PMID- 25130069
TI - High preoperative C-reactive protein values predict poor survival in patients on
chronic hemodialysis undergoing nephrectomy for renal cancer.
AB - OBJECTIVES: Previous studies have reported that elevated pretreatment C-reactive
protein (CRP) levels are associated with poor outcome in various malignancies,
including renal cell carcinoma (RCC), in the general population. However, there
is no evidence of such an association in dialysis patients. Therefore, the aim of
this study is to evaluate the prognostic significance of preoperative serum CRP
levels in patients with RCC related to end-stage renal disease (ESRD) requiring
hemodialysis (HD). MATERIALS AND METHODS: We evaluated 315 patients with ESRD
requiring HD who underwent nephrectomy for RCC as the first-line treatment at our
hospital from 1982 to 2013. Complete patient- and tumor-specific characteristics
as well as preoperative CRP levels were assessed. We defined a serum CRP level
>0.5mg/dl as elevated and divided these patients into 2 groups according to their
preoperative CRP levels (CRP<=0.5 and >0.5mg/dl). The median follow-up was 51
months. RESULTS: Preoperative CRP levels were elevated in 75 patients (23.8%).
The Kaplan-Meier 5-year cancer-specific survival rates were 95.2% and 69.9% in
patients with CRP levels<=0.5 and>0.5mg/dl, respectively (P<0.0001). Multivariate
analysis identified preoperative CRP level as an independent predictor for cancer
specific survival, along with a pathological TNM stage and tumor grade (CRP>0.5:
hazard ratio = 3.47; 95% CI: 1.35-9.18; P = 0.0098). The concordance index of
multivariable base models increased after including the preoperative CRP levels.
CONCLUSIONS: Preoperative serum CRP level might be an independent predictor of
postoperative survival in patients with RCC related to ESRD requiring HD. Its
routine use, together with the TNM classification and tumor grade, could allow
better risk stratification and risk-adjusted follow-up of these patients.
PMID- 25130070
TI - PEG mediated synthesis and biological evaluation of asymmetrical pyrazole
curcumin analogues as potential analgesic, anti-inflammatory and antioxidant
agents.
AB - The new series of asymmetrical pyrazole curcumin analogues 4a-g were synthesized
by using polyethylene glycol (PEG-400) as a green reaction medium and evaluated
for their in vivo analgesic and in vitro antioxidant (H2 O2 , DPPH, Ferrous
reducing power and Nitric oxide scavenging activity) and anti-inflammatory
activities. All the compounds synthesized 4a-g showed the potential to
demonstrate analgesic activity as compared to the standard ibuprofen. Among the
tested series, compounds 4e and 4b exhibited good hydrogen peroxide scavenging
activity as compared to the standard butylated hydroxy toluene (BHT). Compounds
4b, 4d, 4f, and 4g showed good DPPH free radical scavenging activity. Compounds
4b, 4c, 4d, 4e and 4g showed excellent ferrous-reducing power activity, whereas
all the compounds showed better nitric oxide scavenging activity than standard
ascorbic acid. Additionally, all the synthesized compounds were also screened for
their in vitro anti-inflammatory activity. Compounds 4b, 4d, 4f and 4g showed
good anti-inflammatory activity as compared to standard diclofenac sodium.
PMID- 25130071
TI - Isolation of Enterococcus faecium NM113, Enterococcus faecium NM213 and
Lactobacillus casei NM512 as novel probiotics with immunomodulatory properties.
AB - Probiotics, defined as living bacteria that are beneficial for human health,
mainly function through their immunomodulatory abilities. Hence, these
microorganisms have proven successful for treating diseases resulting from immune
deregulation. The aim of this study was to find novel candidates to improve on
and complement current probiotic treatment strategies. Of 60 lactic acid
bacterial strains that were isolated from fecal samples of healthy, full-term,
breast-fed infants, three were chosen because of their ability to activate human
immune cells. These candidates were then tested with regard to immunomodulatory
properties, antimicrobial effects on pathogens, required pharmacological
properties and their safety profiles. To identify the immunomodulatory structures
of the selected isolates, activation of specific innate immune receptors was
studied. The three candidates for probiotic treatment were assigned Enterococcus
faecium NM113, Enterococcus faecium NM213 and Lactobacillus casei NM512. Compared
with the established allergy-protective strain Lactococcus lactis G121, these
isolates induced release of similar amounts of IL-12, a potent inducer of T
helper 1 cells. In addition, all three neonatal isolates had antimicrobial
activity against pathogens. Analysis of pharmacological suitability showed high
tolerance of low pH, bile salts and pancreatic enzymes. In terms of safe
application in humans, the isolates were sensitive to three antibiotics
(chloramphenicol, tetracycline and erythromycin). In addition, the Enterococcus
isolates were free from the four major virulence genes (cylA, agg, efaAfs and
ccf). Moreover, the isolates strongly activated Toll-like receptor 2, which
suggests lipopeptides as their active immunomodulatory structure. Thus, three
novel bacterial strains with great potential as probiotic candidates and
promising immunomodulatory properties have here been identified and
characterized.
PMID- 25130073
TI - Relationship between oral bacteria count and pneumonia onset in elderly nursing
home residents.
AB - AIM: Oral bacteria, which are a source of infection for aspiration pneumonia,
were examined in frail older adults with the aim of establishing a standard
bacteria count that indicates the risk of pneumonia onset in this group. METHODS:
A survey of bacteria count in the saliva using a simple instrument for
measurement of the number of oral bacteria, along with factors including
swallowing function and nutritional status, was carried out in 691 elderly
individuals requiring care (137 men; mean age 82.6 +/- 8.3 years; 554 women; mean
age 88.0 +/- 7.1 years; total mean age 86.7 +/- 7.8 years) at 16 nursing homes in
Japan. All participants gave their consent for inclusion in the present study.
During a 6-month follow-up period, participants who developed pneumonia were
identified, and relationships between the factors measured at the start of the
period and pneumonia onset were examined. RESULTS: During the 6-month follow-up
period, 33 participants (4.8%; 5 men, 28 women; mean age 88.3 +/- 7.4 years)
developed pneumonia. Pneumonia onset was significantly associated with reduced
activities of daily living, swallowing dysfunction and undernourishment. Logistic
regression analysis identified a saliva bacteria count of 10(8.5) colony-forming
units/mL as an independent explanatory factor for pneumonia onset (P = 0.012, RR
= 3.759). CONCLUSIONS: Oral bacteria count of 10(8.5) colony-forming units/mL
saliva in an elderly person requiring care was identified as a risk factor for
pneumonia onset.
PMID- 25130072
TI - Immune response of gammadeltaT cells in Schistosome japonicum-infected C57BL/6
mouse liver.
AB - Systematic evaluation of the role of gammadeltaT cells during the Schistosoma
japonicum infection has not been reported, despite the fact that gammadeltaT
cells contribute to many infectious diseases in innate immunity. Therefore, the
aim of this study was to observe the properties of gammadeltaT cells in the liver
of C57BL/6 mice infected by S. japonicum. In this report, using immuno
fluorescent histological analysis, gammadeltaT cells were found around hepatic
granulomatous. Moreover, the flow cytometry results revealed that the percentage
of hepatic gammadeltaT cells increased significantly after S. japonicum
infection. More interestingly, a subset of CD3(-)gammadeltaTCR(+) cells were
found and markedly increased after infection. Furthermore, expression of
activation markers (CD25 and CD69) and cytokine profiles were detected in these
hepatic CD3(+)gammadeltaTCR(+) and CD3(-)gammadeltaTCR(+) cells. The
significantly higher level of CD69, IL-4 and IL-17 were observed in
CD3(+)gammadeltaTCR(+) cells after infection, suggesting that
CD3(+)gammadeltaTCR(+) cells instead of CD3(-)gammadeltaTCR(+) cells might play a
predominant role during the infection. Finally, our results indicated that the
expression of NKG2D on CD3(+)gammadeltaTCR(+) cells was higher than that on CD3(
)gammadeltaTCR(+) cells. Collectively, gammadeltaT cells could play an important
role in the liver of C57BL/6 mouse during japonicum infection.
PMID- 25130074
TI - Modalities of fetal evaluation to detect fetal compromise prior to the
development of significant neurological damage.
AB - AIMS: The aim of this study was to clarify the developmental mechanism underlying
fetal heart rate (FHR) long-term variability (LTV) and acceleration with respect
to fetal brain damage. MATERIAL AND METHODS: The fetal state was deduced from the
developmental mechanism of FHR variability analyzed by actocardiogram, animal
experiments, and simulations. RESULTS: LTV develops due to minor fetal movements
in the fetal midbrain, moderate LTV by fetal periodic movements and triangular
accelerations by large fetal movement bursts. Stimulation of the fetal midbrain
by sound and light produces fetal movements that lead to FHR acceleration. Severe
hypoxia can result in the loss of LTV and neuronal necrosis that may damage the
fetal brain. Therefore, a cesarean section is recommended prior to the loss of
LTV, rather than after its loss. The vagal center of the fetal medulla oblongata
is excited by hypoxia and produces FHR bradycardia. The heart rate of hypoxic
rabbits was found to be closely correlated with the PaO2, thus the impact of
hypoxia could be estimated by the hypoxia index, which is calculated from the
reciprocal of nadir FHR and bradycardia duration. CONCLUSIONS: Analyzing the
development of FHR signs could help to diagnose fetal state. An early cesarean
section is recommended before the loss of LTV as indicated by the hypoxia index,
which will contribute to prevent fetal brain damage and neurological sequels.
PMID- 25130076
TI - Causes of readmission after operation for congenital heart disease.
AB - BACKGROUND: Readmission after operations for congenital heart conditions has
significant implications for patient care. Readmission rates vary between 8.7%
and 15%. The aim of this study was to determine the incidence, causes, and risk
factors associated with readmission. METHODS: 811 consecutive patients undergoing
operations for congenital heart conditions were analyzed. Readmission was defined
as admission to any hospital within 30 days of discharge for any cause.
Demographic, preoperative, operative, and postoperative variables were evaluated.
Univariate comparisons were made between the nonreadmission and readmission
groups, and multivariate logistic regression analysis was made to determine
independent risk factors for readmission. RESULTS: There were a total of 92
readmissions in 79 patients (9.7%). The reasons included cardiac (36, 39%),
pulmonary (20, 22%), gastrointestinal (13, 14%), infectious (20, 22%), and other
adverse events (2, 2%). Patients with either single-ventricle palliation or
nasogastric feeding accounted for 40 (50%) readmissions. On univariate analysis,
there were significant differences between readmitted and nonreadmitted patients
in relation to patient age, chromosomal abnormality, mortality risk score,
duration of mechanical ventilation, postoperative length of stay, single
ventricle physiology, and nasogastric feeding at discharge (p < 0.05). On
multivariate analysis, significant risk factors for readmission were single
ventricle physiology (odds ratio [OR] 2.39; 95% confidence interval [CI] 1.28 to
4.47; p=0.005), preoperative arrhythmia (OR 2.59; 95% CI 1.02 to 6.59; p=0.04),
longer postoperative length of stay (OR 2.2; 95% CI 1.22 to 3.99; p=0.008), and
nasogastric tube feeding at discharge (OR 2.2; 95% CI 1.15 to 4.19; p=0.01).
CONCLUSIONS: The incidence of readmission after operations for congenital cardiac
conditions remains high. Efforts focusing on patients with single-ventricle
palliation and those with preoperative arrhythmia, prolonged postoperative length
of stay and nasogastric tube feeding at discharge may be particularly beneficial.
PMID- 25130075
TI - Posterior papillary muscle anchoring affects remote myofiber stress and pump
function: finite element analysis.
AB - BACKGROUND: The role of posterior papillary muscle anchoring (PPMA) in the
management of chronic ischemic mitral regurgitation (CIMR) is controversial. We
studied the effect of anchoring point direction and relocation displacement on
left ventricular (LV) regional myofiber stress and pump function. METHODS:
Previously described finite element models of sheep 16 weeks after posterolateral
myocardial infarction (MI) were used. True-sized mitral annuloplasty (MA) ring
insertion plus different PPM anchoring techniques were simulated. Anchoring
points tested included both commissures and the central anterior mitral annulus;
relocation displacement varied from 10% to 40% of baseline diastolic distance
from the PPM to the anchor points on the annulus. For each reconstruction
scenario, myofiber stress in the MI, border zone, and remote myocardium as well
as pump function were calculated. RESULTS: PPMA caused reductions in myofiber
stress at end-diastole and end-systole in all regions of the left ventricle that
were proportional to the relocation displacement. Although stress reduction was
greatest in the MI region, it also occurred in the remote region. The maximum 40%
displacement caused a slight reduction in LV pump function. However, with the
correction of regurgitation by MA plus PPMA, there was an overall increase in
forward stroke volume. Finally, anchoring point direction had no effect on
myofiber stress or pump function. CONCLUSIONS: PPMA reduces remote myofiber
stress, which is proportional to the absolute distance of relocation and
independent of anchoring point. Aggressive use of PPMA techniques to reduce
remote myofiber stress may accelerate reverse LV remodeling without impairing LV
function.
PMID- 25130077
TI - Myocardial perfusion, scarring, and function in anomalous left coronary artery
from the pulmonary artery syndrome: a long-term analysis using magnetic resonance
imaging.
AB - BACKGROUND: Anomalous left coronary artery from the pulmonary artery (ALCAPA) is
a rare congenital heart defect. We aimed to examine the role of cardiac magnetic
resonance imaging (MRI) in the long-term surveillance of repaired ALCAPA with
regard to myocardial scarring, wall motion abnormalities, perfusion deficits, and
myocardial function. METHODS: Twenty-one patients after direct reimplantation of
ALCAPA (median age at operation, 2.8 years) were examined after a median 10.6
years by MRI at rest and under dobutamine stress conditions, echocardiography,
and ergometry. Results were compared with preoperative, immediately postoperative
(5 days), and intermediate-term (5.8 years) echocardiography. RESULTS: No early
or late deaths occurred. Improvements in indexed left ventricular end-diastolic
dimension, ejection fraction, and mitral valve function were observed in all
patients. However, MRI at rest showed wall motion abnormalities in 67% and
perfusion deficits in 28%. Myocardial scars were seen in 67%. Dobutamine stress
MRI detected wall motion abnormalities in 19% and perfusion deficits in 14%,
which were not seen on MRI at rest. Exercise testing did not reflect cardiac
dysfunction. CONCLUSIONS: Although long-term follow-up showed global left
ventricular function had improved after ALCAPA repair, MRI showed left
ventricular wall motion abnormalities, perfusion deficits, and myocardial
scarring were seen in many patients. Dobutamine stress MRI identified deficits
that were not evident on MRI at rest, and can therefore be considered a valuable
surveillance tool. These results suggest the need for lifelong surveillance of
repaired ALCAPA.
PMID- 25130078
TI - Congenital cardiac lesions involving systolic flow abnormalities are associated
with platelet dysfunction in children.
AB - BACKGROUND: Shear stress-induced platelet dysfunction (PD) is prevalent among
adults with aortic stenosis. Our aim was to determine whether abnormal platelet
function was associated with specific congenital cardiac lesions in children.
METHODS: The charts of 407 children who had undergone cardiopulmonary bypass and
had preoperative platelet function analysis were evaluated. Patients were
assigned to 1 of 11 different lesion categories. Platelet dysfunction (PD) was
defined as prolonged closure time (CT) as measured with a platelet function
analyzer. Odds ratio (OR) estimates for prolonged CT were calculated for each
lesion category. Mean CTs were compared with Tukey-Kramer separated means
testing. Analysis of variance modeling was used to determine association between
hematocrit value and CT. RESULTS: CT in patients with ventricular septal defects
(VSD) and right ventricular outflow tract obstruction (RVOTO) lesions was
prolonged. OR analysis found that patients with VSDs (OR, 2.46) or RVOTO (OR,
2.88) had at least a 95% probability of an abnormal CT. In contrast, patients
with atrial septal defect (ASD), bidirectional Glenn procedure (BDG), and
pulmonary insufficiency (PI) had a reduced probability of a prolonged CT (p <
0.05). A similar pattern was seen in parametric analysis comparing mean CTs
across lesion categories. A lower preoperative hematocrit value was associated
with prolonged CTs across all lesion types (p < 0.05). CONCLUSIONS: PD was common
in children with congenital cardiac lesions involving systolic flow abnormalities
and was uncommon among children with lesions having diastolic abnormalities.
Lower preoperative hematocrit values were associated with prolonged CTs,
suggesting subclinical bleeding secondary to excessive platelet shearing.
PMID- 25130079
TI - Impact of neonatal versus nonneonatal total repair of tetralogy of fallot on
growth in the first year of life.
AB - BACKGROUND: Optimal timing for total repair in tetralogy of Fallot (TOF) is
controversial. We aimed to determine if weight at 1 year differs between patients
who undergo neonatal total repair versus those who undergo nonneonatal total
repair later in the first year of life. METHODS: A retrospective review of
infants admitted with TOF between January 2004 and June 2011 was conducted.
Patient data, including weight, were collected throughout the first year of life,
and neonatal total repair versus nonneonatal total repair groups were compared.
RESULTS: Of 163 infants, neonatal total repair was undertaken in 36 (22%) of
them, whereas 127 (78%) infants had nonneonatal total repair at greater than 28
days of life. The median neonatal intensive care unit length of stay (LOS) was
longer for the neonatal total repair group than for the nonneonatal total repair
group (17.5 [11-24] versus 7 [0-15] days; p < 0.001). Patients in the neonatal
total repair group were more likely to have a transannular patch (TAP) (p <
0.001) than were those in the nonneonatal total repair group, whereas patients in
the nonneonatal total repair group were more likely to have undergone a valve
sparing operation (p = 0.002). The mean weight-for-age z score was 0.7 higher in
the neonatal total repair group compared with the nonneonatal total repair group
(p = 0.03) controlling for birth weight (BW), diagnostic subgroup, and
gestational age (GA). CONCLUSIONS: Patients with TOF who underwent neonatal total
repair were more likely to receive a TAP but had higher weight-for-age scores at
1 year compared with patients who underwent full repair later in the first year
of life.
PMID- 25130080
TI - A half-sandwich organometallic single-ion magnet with hexamethylbenzene
coordinated to the Dy(III) ion.
AB - A half-sandwich organolanthanide complex, [(C6Me6)Dy(AlCl4)3], in which Dy(III)
is coordinated with a pi-bonded arene was synthesized and magnetically
characterized. This complex displays slow magnetic relaxation and a hysteresis
loop associated with single-ion magnet behavior. The orientation of the magnetic
anisotropy axis is analyzed using ab initio calculations.
PMID- 25130081
TI - Prognostic role of hyponatremia in 564 small cell lung cancer patients treated
with topotecan.
AB - OBJECTIVES: Hyponatremia is reported in about 15% of small cell lung cancer
(SCLC). Variable results of the prognostic significance of low plasmatic sodium
(Napl) have been reported. Our study was performed to investigate the prognostic
role of hyponatremia in SCLC patients treated in second-line with topotecan
chemotherapy. MATERIALS AND METHODS: Data were retrospectively collected from a
database including clinical data from 631 patients enrolled in 6 prospective
topotecan iv studies. Final data were obtained from 564 patients in which data on
baseline Napl were available. Univariate and multivariate analysis were carried
out to study the possible correlation between Napl and second-line clinical
outcomes. RESULTS: Hyponatremia (Napl<135mequiv./l) was present in 101 cases
(17.9%). Napl was <125mequiv./l in 16 patients (2.8%), 126-130mequiv./l in 11
(2%), 130-134mequiv./l in 74 (13.1%), while 463 patients (82.1%) showed normal
values. The median survival was 28.7 weeks in patients with normal Napl, and 21.1
weeks in patients with hyponatremia (p<0.0001, HR=1.67, 95%CI=1.32-2.10). By Cox
multivariate analysis, hyponatremia was associated with poorer prognosis
(p=0.0024, HR=1.44, 95%CI=1.13-1.82). A not statistically significant trend of
correlation between hyponatremia and progression-free survival (p=0.085, HR=1.23,
95%CI 0.97-1.55) and response rate (p=0.5037, OR=0.81, 95%CI 0.44-1.49) was
observed. CONCLUSION: Hyponatremia is an independent prognostic factor for
patients with SCLC treated with topotecan in second-line setting. Further studies
are needed to prospectically confirm these results and to develop an optimal
therapy for hyponatremic patients.
PMID- 25130082
TI - Lung cancer in the era of Greek economic crisis.
PMID- 25130083
TI - Metastatic sites and survival in lung cancer.
AB - OBJECTIVES: Population-based data on metastatic sites and survival in site
specific metastases are lacking for lung cancer and for any cancer because most
cancer registries do not record metastases. This study uses a novel population
based approach to identify metastases from both death certificates and national
inpatient data to describe metastatic pathways in lung cancer patients. MATERIALS
AND METHODS: 17,431 deceased lung cancer patients diagnosed 2002-2010 were
identified from the nationwide Swedish Cancer Registry, which is based on
compulsory reports. The influence of age at diagnosis, sex, and histological
subtype on metastatic spread was investigated. Survival in metastatic lung cancer
was assessed by histology and metastatic site. RESULTS: The most frequent
metastatic sites were the nervous system, bone, liver, respiratory system, and
adrenal gland. Liver (35%) and nervous system (47%) metastases were common in
patients with metastases from small cell lung cancer, and bone (39%) and
respiratory system (22%) metastases in adenocarcinoma. Women (43% vs. 35%) and
younger patients had more metastases to the nervous system. Median survival after
diagnosis was 13 months for non-metastatic and five months for metastatic lung
cancer. In this novel data, liver metastases conferred the worst prognosis (three
months), especially for large cell histology. Bone metastases also featured poor
survival, whereas survival in respiratory and nervous system metastases was
better. CONCLUSION: Metastatic sites and survival in metastatic lung cancer is
influenced by sex, histological subtype, and age at diagnosis. Liver and bone
metastases signal poor survival, compared with nervous system metastases.
PMID- 25130085
TI - Chiral speciation of selenoamino acids in biological samples.
AB - In this paper, the "state of the art" of chiral speciation of selenoamino acids
(SeAAs) in biological samples is critically reviewed. The significance and the
features of such studies are highlighted. A special focus lies on chiral
speciation of SeAAs by hyphenation techniques in which a chiral separation method
(such as gas chromatography (GC), high performance liquid chromatography (HPLC)
and capillary electrophoresis (CE)) is on-line coupled with an elemental specific
detector, especially inductively coupled plasma mass spectrometry (ICP-MS). The
advances in the development and application of hyphenation techniques in chiral
speciation of SeAAs in biological samples are summarized and a perspective for
future developments including sophisticated and innovative applications is
discussed. Overall, HPLC-ICP-MS is more applicable than GC/CE-ICP-MS for chiral
speciation of SeAAs. In the future, more novel chiral HPLC methods with high
enantio-resolution, low cost and robustness, and their more applications in real
biological samples analysis are expected.
PMID- 25130084
TI - A phase II trial evaluating the clinical and immunologic response of HLA-A2(+)
non-small cell lung cancer patients vaccinated with an hTERT cryptic peptide.
AB - OBJECTIVES: The immunological and clinical responses of patients with NSCLC
treated, in the context of an expanded action program, with the cryptic hTERT
targeting Vx-001 vaccine are presented. MATERIALS AND METHODS: Forty-six HLA
A*0201-positive patients with advanced NSCLC and residual (n=27) or progressive
(n=19) disease following front-line treatment received two subcutaneous
injections of the optimized TERT572Y peptide followed by four injections of the
native TERT572 peptide, every 3 weeks. Peptide-specific immune responses were
monitored by enzyme-linked immunosorbent spot assay at baseline, and after the
2nd and the 6th vaccinations. Thirty-eight HLA-A*0201-positive matched patients
were used as historical controls. RESULTS: Twenty-three patients (50%) completed
the vaccination protocol and 87% received at least two administrations. Twelve
patients (26%) without disease progression after the 6th vaccination received
boost vaccinations. Three (7%) patients achieved a partial response and 13 (28%)
disease stabilization. The disease control rate was significantly higher in
patients with non-squamous histology compared to those with squamous-cell
histology [n=14 (45%) versus n=2 (13%); p=0.03]. The median progression-free
survival (PFS) and overall survival (OS) was 3.8 (range, 0.7-99.4) and 19.8
months (range, 0.7-99.4), respectively. Patients who developed immune response
had a numerically higher PFS compared to those who failed to mount any (6.7
versus 2.7 months; p=0.090). However, the median OS for the immune-responders was
significantly prolonged compared to non-responders (40.0 versus 9.2 months,
respectively; p=0.02). Toxicity was =24 kg/m2)
nulliparous women, 14 developed non-proteinuric PIH and 12 developed proteinuric
PIH (preeclampsia), whereas 46 had normotensive pregnancies. Insulin sensitivity
was assessed via the whole-body insulin sensitivity index (ISI) and the
homeostatic model of assessment - insulin resistance (HOMA-IR) at 24 weeks of
gestation. Maternal serum levels of FABP4, high-sensitive C-reactive protein (hs
CRP), total testosterone, and non-protein-bound calculated free testosterone
(cfT) were determined at 24 and 32 weeks. RESULTS: Measures of ISI, HOMA-IR, hs
CRP, testosterone and lipids did not differ at 24 and/or at 32 weeks in women who
were subsequently hypertensive. SBP was higher at all time points and FABP4
levels tended to be higher at 24 and 32 weeks in patients compared to controls.
In logistic regression analysis, baseline FABP4 (OR [95% CI] 1.069 [1.020-1.121],
P = 0.006) and SBP after 10 min standing (OR [95% CI] 1.087 [1.029-1.149], P =
0.003) were associated with the development of PIH. FABP4 levels at 24 weeks did
not correlate with insulin sensitivity. Neither was correlation seen between
FABP4 levels at 24 and 32 weeks, vs. those of hs-CRP and testosterone. DISCUSSION
AND CONCLUSIONS: Serum FABP4 concentration and SBP after 10 min standing in an
orthostatic test at 24 weeks are associated with subsequent development of PIH.
PMID- 25130096
TI - Alkaloids: an overview of their antibacterial, antibiotic-enhancing and
antivirulence activities.
AB - With reports of pandrug-resistant bacteria causing untreatable infections, the
need for new antibacterial therapies is more pressing than ever. Alkaloids are a
large and structurally diverse group of compounds that have served as scaffolds
for important antibacterial drugs such as metronidazole and the quinolones. In
this review, we highlight other alkaloids with development potential. Natural,
semisynthetic and synthetic alkaloids of all classes are considered, looking
first at those with direct antibacterial activity and those with antibiotic
enhancing activity. Potent examples include CJ-13,136, a novel actinomycete
derived quinolone alkaloid with a minimum inhibitory concentration of 0.1 ng/mL
against Helicobacter pylori, and squalamine, a polyamine alkaloid from the
dogfish shark that renders Gram-negative pathogens 16- to >32-fold more
susceptible to ciprofloxacin. Where available, information on toxicity, structure
activity relationships, mechanisms of action and in vivo activity is presented.
The effects of alkaloids on virulence gene regulatory systems such as quorum
sensing and virulence factors such as sortases, adhesins and secretion systems
are also described. The synthetic isoquinoline alkaloid virstatin, for example,
inhibits the transcriptional regulator ToxT in Vibrio cholerae, preventing
expression of cholera toxin and fimbriae and conferring in vivo protection
against intestinal colonisation. The review concludes with implications and
limitations of the described research and directions for future research.
PMID- 25130097
TI - Human, food and animal Campylobacter spp. isolated in Portugal: high genetic
diversity and antibiotic resistance rates.
AB - Infections by Campylobacter jejuni and Campylobacter coli are considered the
major cause of bacterial gastroenteritis in humans, with food being the main
source of infection. In this study, a total of 196 Campylobacter strains (125
isolates from humans, 39 from retail food and 32 from food animal sources)
isolated in Portugal between 2009 and 2012 were characterised by multilocus
sequence typing (MLST) and flaA short variable region (SVR) typing.
Susceptibility to six antibiotics as well as the mechanisms underlying antibiotic
resistance phenotypes was also studied. Based on MLST typing, C. coli strains
were genetically more conserved, with a predominant clonal complex (CC828), than
C. jejuni strains. In contrast, C. coli isolates were genetically more variable
than C. jejuni with regard to flaA-SVR typing. A high rate of resistance was
observed for quinolones (100% to nalidixic acid, >90% to ciprofloxacin) and, in
general, resistance was more common among C. coli, especially for erythromycin
(40.2% vs. 6.7%). In addition, most isolates (86%) were resistant to multiple
antimicrobial families. Besides the expected point mutations associated with
antibiotic resistance, detected polymorphisms in the cmeABC locus likely play a
role in the multiresistant phenotype. This study provides for the first time an
overview of the genetic diversity of Campylobacter strains from Portugal. It also
shows a worrying antibiotic multiresistance rate and the emergence of
Campylobacter strains resistant to antibiotics of human use.
PMID- 25130099
TI - Value of integron detection for predicting antibiotic resistance in patients with
Gram-negative septicaemia.
AB - Multidrug-resistant Enterobacteriaceae are a major public health threat and
complicate the choice of drugs for empirical antibiotic therapy, especially in
sepsis patients who require rapid, appropriate treatment. The objective of this
study was to examine the value of integrons as a global predictive marker of
acquired antibiotic resistance in septicaemia-causing Enterobacteriaceae by
direct detection in positive blood cultures. The integron genetic marker can be
detected in a single test, whereas multiple PCRs are needed to detect the
hundreds of known antibiotic resistance genes. A total of 166 positive blood
cultures were included in the study, and integrons were detected with a
quantitative PCR method both in positive blood cultures and isolated
Enterobacteriaceae. The results of integron detection directly on positive blood
cultures were consistent in 98.8% of cases with integron detection in isolated
Enterobacteriaceae. Negative predictive values (NPVs) were >90% for resistance to
third-generation cephalosporins, aminoglycosides, ciprofloxacin and
trimethoprim/sulfamethoxazole. In the current context of antibiotic stewardship,
these good NPVs indicate that this method might be useful for preserving broad
spectrum antibiotics. The results of this proof-of-concept study must be
confirmed in order to demonstrate the clinical relevance of integron detection,
not only in positive blood cultures but also, to gain time, in raw biological
samples.
PMID- 25130100
TI - Background activities, induction, and behavioral allocation in operant
performance.
AB - In experiments on operant behavior, other activities, called "background"
activities, compete with the operant activities. Herrnstein's (1970) formulation
of the matching law included background reinforcers in the form of a parameter
rO, but remained vague about the activities (BO) that produce rO. To gain more
understanding, we analyzed data from three studies of performance with pairs of
variable-interval schedules that changed frequently in the relative rate at which
they produced food: Baum and Davison (2014), Belke and Heyman (1994), and Soto,
McDowell, and Dallery (2005). Results sometimes deviated from the matching law,
suggesting variation in rO. When rO was calculated from the matching equation,
two results emerged: (a) rO is directly proportional to BO, as in a ratio
schedule; and (b) rO and BO depend on the food rate, which is to say that BO
consists of activities induced by food, as a phylogenetically important event.
Other activities unrelated to food (BN ) correspond to Herrnstein's original
conception of rO and may be included in the matching equation. A model based on
Baum's (Baum, 2012) concepts of allocation, induction, and contingency explained
the deviations from the matching law. In the model, operant activity B, BO, and
BN competed unequally in the time allocation: B and BO both replaced BN , BO
replaced lever pressing (Soto et al.), and key pecking replaced BO (Baum &
Davison). Although the dependence of rO and BO on food rate changes Herrnstein's
(1970) formulation, the model preserved the generalized matching law for operant
activities by incorporating power-function induction.
PMID- 25130098
TI - Surveillance study of Treponema pallidum harbouring tetracycline resistance
mutations in patients with syphilis.
PMID- 25130102
TI - Superficial siderosis and spinal intradural extramedullary cavernous angioma.
PMID- 25130101
TI - The anthropometry of children and adolescents may be influenced by the prenatal
smoking habits of their grandmothers: a longitudinal cohort study.
AB - OBJECTIVES: Previously, in the Avon Longitudinal Study of Parents and Children
(ALSPAC), we have shown different sex-specific birth anthropometric measurements
contingent upon whether or not prenatal smoking was undertaken by paternal
grandmother (PGM+/-), maternal grandmother (MGM+/-), and the study mother (M+/-).
The findings raised the question as to whether there were long-term associations
on the growth of the study children over time. METHODS: Measures of weight,
height, body mass index, waist circumference, lean mass, and fat mass of children
in the ALSPAC study from 7 to 17 years of age were used. We compared growth in
four categories at each age: PGM+M- with PGM-M-; MGM+M- with MGM-M-; PGM+M+ with
PGM-M+; MGM+M+ with MGM-M+; and adjusted for housing tenure, maternal education,
parity, and paternal smoking at the start of the study pregnancy. RESULTS: We
found that if the PGM had, but the study mother had not, smoked in pregnancy, the
girls were taller and both genders had greater bone and lean mass. However, if
the MGM had smoked prenatally but the mother had not (MGM+M-), the boys became
heavier than expected with increasing age-an association that was particularly
due to lean rather than fat mass, reflected in increased strength and fitness.
When both the maternal grandmother and the mother had smoked (MGM+M+) girls had
reduced height, weight, and fat/lean/bone mass when compared with girls born to
smoking mothers whose own mothers had not smoked (MGM-M+). CONCLUSIONS: This
study indicates that smoking in humans can have sex-specific transgenerational
effects.
PMID- 25130103
TI - Spasm provocation tests performed under medical therapy: a new approach for
treating patients with refractory coronary spastic angina on emergency admission.
AB - Objective There are no objective methods for evaluating the severity of
vasospasms in patients with refractory coronary spastic angina (R-CSA) under
adequate medical therapy. We examined whether spasm provocation tests performed
under adequate medication are useful for evaluating the severity of disease in R
CSA patients on emergency admission. Methods and Results We performed spasm
provocation tests before and after the administration of medical therapy in eight
R-CSA patients, including one ventricular fibrillation survivor (VF-S) and seven
patients with unstable angina (UAP) on emergency readmission. We also performed
these tests only after medical therapy on urgent admission in four R-CSA
patients, including two patients with UAP, one patient with VF-S and one patient
with acute coronary syndrome. All 12 R-CSA patients had been medicated with >= 2
vasodilator drugs. Positive coronary spasms were defined as >99% transient
narrowing. The coronary artery spasms disappeared in three patients under
medication, and mitigation of vasospasticity was observed in three patients. In
these six cases we continued the same medications. Meanwhile in two patients, we
recommended a consultation for psychosomatic medicine. In contrast, the remaining
six R-CSA patients exhibited higher levels of vasospasticity, irrespective of the
administration of aggressive medical therapy, in which the doses of vasoactive
drugs were increased in order to suppress coronary artery spasms. Conclusion In
some R-CSA patients on emergency admission, performing spasm provocation tests
under medical therapy is useful for determining the subsequent treatment
strategy. Therefore, this test may become a new tool in the treatment of R-CSA.
PMID- 25130104
TI - A pilot study to examine the management of asymptomatic hyperparathyroidism in
Japanese patients in accordance with the guidelines for asymptomatic PHPT
proposed at the Third International Workshop in 2008.
AB - Objective The treatment for asymptomatic primary hyperparathyroidism (PHPT)
remains controversial. In 2008, the Third International Workshop on the
Management of Asymptomatic PHPT proposed a set of guidelines for the management
of asymptomatic PHPT. We therefore evaluated the application of the Workshop
recommendations in Japanese patients with asymptomatic PHPT. Methods We analyzed
each parameter of the guidelines in 87 Japanese patients with asymptomatic PHPT
who underwent methoxy-isobutyl-isonitrile (MIBI) scintigraphy. Results Fewer than
10% of the patients were less than 50 years of age. The bone mineral density T
score was below -2.5 SD in 20 women (46.5% of all women analyzed) and in none of
the men. The eGFR was <60 mL/min/1.73 m(2) in 17 patients. A majority of patients
(43) satisfied only one parameter, while 25 patients satisfied none of the
parameters. Furthermore, the MIBI-positive and surgically treated patients tended
to satisfy a larger number of the parameters. The Workshop criteria and levels of
PTH, daily Ca excretion, serum ALP and 1,25(OH)2 Vitamin D were further analyzed
in relation to the findings of MIBI scans, and almost all of the parameters were
found to be significantly correlated with the results of the MIBI studies.
Conclusion Our results suggest the need to reassess the Workshop guidelines for
the treatment of hyperparathyroidism in Japanese patients. It is desirable that
MIBI scintigraphy be performed whenever possible, as this modality is anticipated
to play an important role in determining whether or not surgery is appropriate.
PMID- 25130105
TI - Oral tacrolimus for megacolon in patients with severe ulcerative colitis.
AB - Toxic megacolon is an infrequent but life-threatening complication that occurs
most commonly in patients with severe ulcerative colitis. Intravenous steroids
are often recommended for patients with toxic megacolon secondary to ulcerative
colitis. However, steroid dependency may mask the presence of intra-abdominal
sepsis and is associated with refractoriness, during which cytomegalovirus
reactivation may occur. In this report, we present two rare cases of megacolon
accompanying pancolonic severe ulcerative colitis that were successfully treated
with oral tacrolimus, including one steroid-naive patient. In cases of ulcerative
colitis with megacolon, treatment with oral tacrolimus is recommended, thereby
avoiding steroid dependency and improving the long-term prognosis.
PMID- 25130106
TI - Successful treatment with entecavir for reactivation of hepatitis B virus
following systemic chemotherapy in a hepatitis B surface antigen-negative patient
with colorectal cancer.
AB - Reactivation of hepatitis B virus (HBV) has recently been reported as a fatal
complication in patients undergoing cytotoxic chemotherapy. We herein describe a
case of reactivation in a 76-year-old man who had undergone pelvic exenteration
for colorectal cancer (CRC). He was treated with a modified FOLFOX6 chemotherapy
regimen after the operation. Thirteen months later, his laboratory data showed
severe liver dysfunction. His hepatitis B surface antigen (HBsAg) test was
positive, and his HBV-DNA level was elevated. We diagnosed the patient with HBV
reactivation as his HBsAg test was negative before starting chemotherapy. His
liver dysfunction improved after administration of entecavir. This is the first
report describing HBV reactivation following chemotherapy for an HBsAg-negative
CRC patient.
PMID- 25130107
TI - Alcoholic liver disease complicated by deep bleeding into the muscles or
retroperitoneum: report of three cases and a review of the literature.
AB - We herein report three cases of alcoholic cirrhosis complicated by deep bleeding.
In two of the three cases, intramuscular or retroperitoneal hematomas developed
spontaneously. In contrast, in the remaining case, an intramuscular hematoma
developed after trauma. In the former two patients, the intramuscular hematomas
recurred at other sites during hospitalization. All three patients received
conservative therapy, and one patient with a retroperitoneal hematoma underwent
transcatheter arterial embolization. All of the patients eventually died of liver
failure. The occurrence of severe alcoholic liver disease with deep bleeding has
recently been reported with increasing frequency, and clinicians should bear this
condition in mind as a life-threatening complication of alcoholic liver disease.
PMID- 25130109
TI - Life-threatening acute heart failure due to primary cardiac undifferentiated
pleomorphic sarcoma.
AB - A 41-year-old man was admitted with acute heart failure and shock status. An
echocardiogram showed a mobile tumor obstructing blood flow through the mitral
valve with a stalk on the posterior left atrium (LA) wall. Emergent open-heart
surgery was performed to resect the tumor (77*36*30 mm). Histological examination
confirmed that it was an undifferentiated pleomorphic sarcoma. Unfortunately,
positron emission tomography performed five months after surgery demonstrated a
local recurrence around the right pulmonary vein and LA. We performed proton beam
radiotherapy to treat the local recurrence, and it was effective. The patient has
survived more than one year since the first life-threatening heart failure
episode.
PMID- 25130108
TI - Double-valve replacement for mitral and aortic regurgitation in a Patient with
Libman-Sacks endocarditis.
AB - A 53-year-old woman with systemic lupus erythematosus and antiphospholipid
syndrome presented with central nervous system (CNS) lupus and vegetation of the
mitral and aortic valves. Her CNS lupus was relieved with methylprednisolone
pulse therapy; however, her mitral regurgitation worsened, and she developed
acute decompensated heart failure. The mitral and aortic valves were replaced
with mechanical heart valves. Microscopic examination of the excised valves
showed no bacterial invasion, and Libman-Sacks (LS) endocarditis of both valves
was confirmed. This was a case of LS endocarditis with clear vegetation that
spread over the mitral and aortic valves.
PMID- 25130110
TI - A rare presentation of subclinical Cushing's syndrome as a pubic fracture.
AB - Osteoporosis and bone fractures are commonly seen in patients with Cushing's
syndrome (CS). Fractures usually occur in the vertebrae and ribs whereas pubic
fractures are less common. Similar to obvious hypercortisolemia, subclinical
hypercortisolemia can increase the risk of fractures. However, in subclinical
cases, bone fractures are very rarely seen as the presenting symptom. We herein
report the case of a 62-year-old postmenopausal woman who was presented with a
pubic fracture. During the evaluation of the fracture, thoracoabdominal magnetic
resonance imaging of the patient demonstrated an adrenal mass. Although the
patient did not show any signs of overt hypercortisolism, an endocrinologic
evaluation revealed hypercortisolism due to an adrenal tumor. Adrenalectomy was
performed, which resulted in a cure of the disease. During the orthopedic follow
up, the patient's pubic area pain gradually improved, and the pubic fracture
healed without any accompanying new bone fractures. One year after the surgery, a
remarkable improvement was detected in the patient's bone density in spite of the
lack of administration of any medications for osteoporosis. Subclinical CS can
present as a pubic fracture, and awareness of this relationship can help
physicians to diagnose the disease.
PMID- 25130111
TI - Coexistence of gastrointestinal stromal tumors (GISTs) and pheochromocytoma in
three cases of neurofibromatosis type 1 (NF1) with a review of the literature.
AB - It is well known that neurofibromatosis type 1 (NF1) is uncommonly associated
with pheochromocytoma development and also, to a larger extent, with
gastrointestinal stromal tumors (GISTs). We herein document three cases with the
rare condition of NF1 coexisting with GIST and pheochromocytoma, while one of
them also has a composite tumor and another has papillary thyroid carcinoma.
PMID- 25130113
TI - A rare case of acquired methemoglobinemia associated with alkaptonuria.
AB - We herein present a rare case of acquired methemoglobinemia associated with
alkaptonuria. Alkaptonuria is a congenital error of metabolism caused by the
deficiency of homogentisic acid oxidase, which subsequently results in the
accumulation of homogentisic acid (HGA) in body tissues. As renal dysfunction
progresses, the level of HGA excretion in the urine decreases and the blood
concentration of HGA increases. HGA oxidizes oxyhemoglobin to methemoglobin,
which can induce multiple organ failure accompanied by tissue hypoxia,
intravascular hemolysis and metabolic acidosis. The mortality of this disease is
high when alkaptonuria is associated with the presence of methemoglobinemia;
therefore, treatment should be carefully planned in such cases.
PMID- 25130112
TI - Liraglutide as a potentially useful agent for regulating appetite in diabetic
patients with hypothalamic hyperphagia and obesity.
AB - Hypothalamic hyperphagia and obesity are characterized by a lack of satiety and
an abnormally high appetite that is difficult to control. We herein report the
cases of two patients with hypothalamic hyperphagia and obesity with MRI
detectable hypothalamic lesions. These patients suffered from diabetes mellitus
associated with an abnormal eating behavior and weight gain. Liraglutide was
successfully used to treat their diabetes mellitus and suppress their abnormal
appetites. Glucagon-like peptide-1 analogues, including liraglutide, are
promising treatment options in patients with hypothalamic hyperphagia and
obesity, as these agents enhance the hypothalamic input of the satiety signal,
which is lacking in such patients.
PMID- 25130114
TI - Marked elevation of serum hyaluronan levels in collagenofibrotic glomerulopathy.
AB - Collagenofibrotic glomerulopathy is a rare glomerular disease characterized by
the massive deposition of type III collagen in mesangial and subendothelial
spaces. We observed markedly increased serum hyaluronan levels in patients with
collagenofibrotic glomerulopathy; levels in three patients were more than 1,000
times greater than the normal upper limit. However, one kidney transplant patient
had normal serum hyaluronan levels. We found that serum levels and activities of
the enzyme hyaluronidase were normal, and hyaluronan was not markedly deposited
in the mesangial or subendothelial spaces. Our findings suggest that serum
hyaluronan levels may be a specific diagnostic marker of collagenofibrotic
glomerulopathy, and kidney transplantation may alleviate marked increases in
serum hyaluronan.
PMID- 25130115
TI - Severe hypokalemia and thyrotoxic paralysis from painless thyroiditis complicated
by life-threatening polymorphic ventricular tachycardia and rhabdomyolysis.
AB - A 61-year-old man presented with lower extremity paralysis and severe
hypokalemia. His thyroid function test showed thyrotoxicosis. Despite attempts to
correct his hypokalemia, he developed pulseless polymorphic ventricular
tachycardia two hours later. He was successfully resuscitated after
defibrillation. We performed continuous venovenous hemodiafiltration for 10 days
due to acute kidney injury and rhabdomyolysis. We observed life-threatening
polymorphic ventricular tachycardia requiring urgent defibrillation, as well as
rhabdomyolysis requiring dialysis during the transient thyrotoxic phase of
painless thyroiditis. Pay attention to the possibility of the development of life
threatening ventricular tachycardia associated with hypokalemia in the setting of
thyroiditis and thyrotoxic paralysis.
PMID- 25130116
TI - Diffuse parenchymal pulmonary amyloidosis showing an objective response to
bortezomib-based chemotherapy.
AB - A 77-year-old woman was admitted because of bilateral hand numbness and dyspnea
on exertion. Her serum IgG was increased, and a bone marrow aspiration analysis
supported a diagnosis of multiple myeloma. Additionally, computed tomography
scans of the chest showed bilateral ground glass attenuations, linear opacities,
and consolidations. Transbronchial lung biopsy revealed Congo Red-positive
amorphous eosinophilic deposits. She was therefore diagnosed with diffuse
parenchymal pulmonary amyloidosis accompanied by multiple myeloma. Following
combination chemotherapy including bortezomib, her serum monoclonal protein
levels were normalized, and pulmonary function and oxygenation improved.
PMID- 25130117
TI - Bevacizumab for critical brain metastases in a patient with pulmonary pleomorphic
carcinoma.
AB - Bevacizumab was initially contraindicated in patients with brain metastases, but
several reports have shown the efficacy and safety of bevacizumab for brain
metastases. We herein report the case of a patient with pulmonary pleomorphic
carcinoma for which bevacizumab plus weekly paclitaxel following whole-brain
radiotherapy (WBRT) was effectively and safely administered for critical and
refractory brain metastases. Although the 50-year-old male patient received WBRT
with anti-edema therapies for progressive brain metastases, his clinical symptoms
deteriorated rapidly. After the completion of WBRT, we administered bevacizumab
plus weekly paclitaxel, and his neurological symptoms improved dramatically.
Brain magnetic resonance imaging demonstrated a marked response by the brain
metastases and improved brain edema. This case suggested both synergism between
WBRT and bevacizumab, and an anti-edema effect of bevacizumab. Bevacizumab may be
therefore a potent therapeutic option for patients with refractory brain
metastases.
PMID- 25130118
TI - Esophagomediastinal fistula secondary to multidrug-resistant tuberculous
mediastinal lymphadenitis.
AB - Esophagomediastinal fistula secondary to mediastinal tuberculosis (TB)
lymphadenitis is a rare and unusual complication. A 32-year-old woman visited our
clinic because of chest pain. Computed tomography (CT) demonstrated an
esophagomediastinal fistula with subcarinal lymphadenopathy and no remarkable
parenchymal lung lesions. The esophagomediastinal fistula was confirmed by
esophagoscopy; however, the patient's bronchoscopy findings were unremarkable.
The endobronchial ultrasound-guided lymph node aspiration did not confirm a
diagnosis of TB. Finally, the patient was diagnosed via a lymph node biopsy. A
drug-sensitivity test revealed the presence of a multidrug-resistant pathogen. To
the best of our knowledge, this is the first case of esophagomediastinal fistula
secondary to multidrug-resistant (MDR-) TB mediastinal lymphadenitis.
PMID- 25130119
TI - Wandering pneumonia caused by dabigatran.
AB - We herein describe the case of a 74-year-old man who experienced pulmonary
consolidation and chest pain following administration of dabigatran, a novel oral
anticoagulant. The consolidation settled spontaneously in another lung area, a
condition sometimes referred to as "wandering pneumonia." Although we did not
find specific pathological evidence of interstitial lung disease on
transbronchial lung biopsy, a lung opacity spontaneously disappeared following
discontinuance of dabigatran, and there was no recurrence. There are no other
reports of dabigatran-induced lung injury, except alveolar hemorrhage and
eosinophilic pneumonia. We should consider that any novel drug could cause
various types of pulmonary injuries.
PMID- 25130120
TI - Chronic thromboembolic pulmonary hypertension complicated by a cavitating lung
infection caused by Mycobacterium intracellulare.
AB - A 35-year-old man with a six-month history of progressive exertional dyspnea was
referred to our institution. He had been diagnosed with Mycobacterium
intracellulare pulmonary infection with lung cavitation two years earlier, and
was being followed up without any medications. After being referred to our
hospital, he underwent computed tomographic pulmonary angiography, which
indicated a pulmonary thrombus and lung cavitation. Furthermore, right heart
catheterization confirmed pulmonary hypertension, and we made a diagnosis of
chronic thromboembolic pulmonary hypertension (CTEPH). Following successful
pulmonary endarterectomy, the patient's symptoms and hemodynamics were
significantly improved, with the disappearance of lung cavitation. It is
important to suspect CTEPH in patients with unaccountable infectious lung
cavities.
PMID- 25130121
TI - Lung adenocarcinoma complicated by Trousseau's syndrome successfully treated by a
combination of anticoagulant therapy and chemotherapy.
AB - A 63-year-old woman was diagnosed with advanced lung adenocarcinoma complicated
by Trousseau's syndrome characterized by non-bacterial thrombotic endocarditis,
asymptomatic brain infarction, deep venous thrombosis, and low-grade disseminated
intravascular coagulation (DIC). The patient's DIC rapidly became widespread, and
multiple micropulmonary embolisms led to severe respiratory failure. She received
a blood transfusion and anticoagulant treatment with heparin and recombinant
human soluble thrombomodulin, which modestly ameliorated her symptoms, and
additional chemotherapy led to tumor shrinkage with concomitant resolution of
Trousseau's syndrome. Although there are no established medical approaches for
managing Trousseau's syndrome, intensive anticoagulant treatment may be effective
for improving the patients' general condition in order for them to be able to
undergo subsequent combination chemotherapy.
PMID- 25130122
TI - Acquired factor X deficiency associated with atypical AL-amyloidosis.
AB - We herein describe the case of a 77-year-old woman with acquired factor X
deficiency that was likely caused by atypical amyloidosis. The patient developed
severe gastrointestinal bleeding as a result of a significant decrease of factor
X activity. Neither proteinuria nor diarrhea was observed as an initial
manifestation. Although a bone marrow examination revealed direct fast scarlet
positive extracellular deposits, they did not exhibit red-to-green dichroism
under polarized light. Immunofluorescence microscopy showed that the fibrillar
proteins were positive for CD138 but negative for beta2-microglobulin or amyloid
A antibodies. These atypical pathological features of immunoglobulin light chain
amyloidosis in this patient might be related to its unique clinical presentation.
PMID- 25130123
TI - Crystalglobulinemia with fulminant course with cylinder-like bodies on peripheral
blood smear.
AB - A 63-year-old woman presented to our hospital with fever, purpura and pain in
both legs and died 4 days after admission. Her blood smear and skin biopsy showed
cylinder-like bodies (20*120 MUm). She was diagnosed to have monoclonal
gammopathy (IgG, lambda type). An autopsy revealed cylinder-like bodies in the
vasculature of various organs. We noted a proliferation of atypical plasma cells
in her bone marrow, suggesting pre-existing myeloma. Crystalglobulinemia is a
rare manifestation of hypergammaglobulinemia that can cause multiple embolisms of
the small vessels, and this resulted in the patient's fulminant course. The
identification of cylinder-like bodies in the peripheral blood may help in
reaching a diagnosis in such cases.
PMID- 25130124
TI - Bortezomib-induced posterior reversible encephalopathy syndrome: clinical and
imaging features.
AB - Posterior reversible encephalopathy syndrome (PRES) is a rare and potentially
harmful complication in patients receiving targeted chemotherapy. We herein
present a case of PRES that occurred after 33 days of high-dose bortezomib
treatment and propose both overwhelmed cerebral autoregulation and toxin-mediated
blood-brain barrier damage as the underlying mechanisms based on the imaging
findings. A favorable recovery was observed two days after achieving stringent
hypertension control and withholding bortezomib. Follow-up images obtained two
weeks later unveiled a dramatic remission, with faint areas of subcortical
hyperintensity in the bilateral parieto-occipital regions. With explicit clinical
and imaging features, this case highlights the need for early recognition of PRES
during the clinical course of bortezomib therapy.
PMID- 25130125
TI - An aberrant subclavian artery exhibiting the partial steal phenomenon in a
patient with VACTERL association.
AB - We herein report the case of a 22-year-old Caucasian man with known vertebral
defects, anal atresia, tracheoesophageal fistula with esophageal atresia, cardiac
defects, renal and limb anomalies (VACTERL) association who presented with a
headache and vertigo following the sudden and temporary loss of consciousness
while attending a concert four days before admission to the hospital. On a
physical examination, the following findings were found: a low body height, low
set ears, thoracic scoliosis and a mild holosystolic heart murmur. A
neurosonological examination revealed a partial subclavian steal phenomenon. CT
angiography of the neck vessels and aortic arch confirmed an anomalous right
subclavian artery -known as the lusorian artery. Further studies are warranted in
patients with VACTERL in order to identify possible links between the prevalence
of an aberrant right subclavian artery (lusorian artery) and possible congenital
subclavian steal syndrome or dysphagia lusoria. In addition, duplex ultrasound of
the carotid and vertebral arteries may be performed as part of screening
examinations in patients with congenital syndromes.
PMID- 25130126
TI - Spinal intradural extramedullary cavernous angioma presenting with superficial
siderosis and hydrocephalus: a case report and review of the literature.
AB - A 36-year-old man with progressive hearing impairment visited our hospital
complaining of a severe headache. A neurological examination revealed bilateral
sensorineural hearing impairment, mild ataxia, hyperreflexia and mild cognitive
dysfunction. Brain MRI demonstrated hydrocephalus and typical hypointensity
rimming the brain surface on T2(*)-weighted images. The patient was diagnosed as
having superficial siderosis. Spinal MRI disclosed the presence of a lumbar
intradural extramedullary mass. The surgically resected tumor was histologically
found to be a cavernous angioma. Superficial siderosis is an important cause of
hearing loss. With respect to the detection of disorders underlying this
pathological condition, MRI examinations, including those of the brain and whole
spinal cord, are recommended.
PMID- 25130127
TI - A rare case of diffuse pulmonary nodules in a patient with adult-onset Still's
disease.
AB - Adult-onset Still's disease (AOSD) is a multisystemic inflammatory disorder, but
pulmonary involvement is rare. We herein describe the case of a woman diagnosed
with AOSD; treatment resolved her symptoms, but nine days later she was admitted
with pyrexia and a productive cough. A chest X-ray revealed diffuse pulmonary
nodules and patchy shadows. A high-resolution chest computed tomography scan
confirmed diffuse infiltration in the pulmonary parenchyma, signs of alveolar
nodules, distribution along the lobule center, several areas of tree-in-bud
patterns, and bilateral pleural effusion. The patient was treated with high doses
of corticosteroids, which rapidly reduced the size of her diffuse pulmonary
nodules and dramatically improved her pleural effusion.
PMID- 25130128
TI - Grade 3 lymphomatoid granulomatosis in a patient receiving methotrexate therapy
for rheumatoid arthritis.
AB - Lymphomatoid granulomatosis (LyG) is a rare, B-cell derived, lymphoproliferative
disorder that often presents as pulmonary nodular lesions with a histopathology
of lymphatic invasion of the vascular wall. The development of LyG may be
associated with reactivation of the Epstein-Barr virus under an immunosuppressive
state. We herein report a case of Grade 3 LyG that developed during methotrexate
therapy for rheumatoid arthritis and regressed following the withdrawal of the
drug.
PMID- 25130129
TI - Elizabethkingia meningoseptica as an unusual pathogen causing healthcare
associated bacteriuria.
AB - Elizabethkingia meningoseptica is recovered from urine samples in very unusual
cases, although the clinical significance of its detection remains unclear. Four
cases of E. meningoseptica bacteriuria were analyzed, and E. meningoseptica was
found to be the causative agent of healthcare-associated bacteriuria, including
urinary tract infections, asymptomatic bacteriuria and transient bacteriuria,
primarily in elderly patients with diabetes. Although E. meningoseptica cultured
from urine was found to be resistant to most antimicrobial agents, bacteriuria
caused by E. meningoseptica resolved in all four cases. However, instances of
death have also been previously reported.
PMID- 25130130
TI - Prevotella brain abscesses and stroke following dental extraction in a young
patient: a case report and review of the literature.
AB - A brain abscess is a life-threatening infection. There are few reports describing
Prevotella bacteremia with middle cerebral artery (MCA) occlusion and brain
abscess following dental extraction in the literature. We herein describe a 32
year-old healthy man who experienced headache after tooth extraction. He was not
correctly diagnosed until he experienced a stroke and a blood culture revealed
Prevotella denticola weeks later. This case and our detailed review of related
cases highlight the importance of thorough medical history-taking and clinical
evaluations. Brain abscess formation should be considered in previously healthy
patients with fever, stroke, and a recent history of tooth extraction.
PMID- 25130131
TI - Spontaneous esophageal perforation with a posterior mediastinal hematoma.
PMID- 25130132
TI - Localized infarction of the lateral geniculate body.
PMID- 25130134
TI - Reducing radiation, revising reference levels.
PMID- 25130133
TI - Exploring arrays of vertical one-dimensional nanostructures for cellular
investigations.
AB - The endeavor of exploiting arrays of vertical one-dimensional (1D) nanostructures
(NSs) for cellular applications has recently been experiencing a pronounced surge
of activity. The interest is rooted in the intrinsic properties of high-aspect
ratio NSs. With a height comparable to a mammalian cell, and a diameter 100-1000
times smaller, NSs should intuitively reach far into a cell and, due to their
small diameter, do so without compromising cell health. Single NSs would thus be
expedient for measuring and modifying cell response. Further organization of
these structures into arrays can provide up-scaled and detailed spatiotemporal
information on cell activity, an achievement that would entail a massive leap
forward in disease understanding and drug discovery. Numerous proofs-of-principle
published recently have expanded the large toolbox that is currently being
established in this rapidly advancing field of research. Encouragingly, despite
the diversity of NS platforms and experimental conditions used thus far, general
trends and conclusions from combining cells with NSs are beginning to
crystallize. This review covers the broad spectrum of NS materials and dimensions
used; the observed cellular responses with specific focus on adhesion,
morphology, viability, proliferation, and migration; compares the different
approaches used in the field to provide NSs with the often crucial cytosolic
access; covers the progress toward biological applications; and finally,
envisions the future of this technology. By maintaining the impressive rate and
quality of recent progress, it is conceivable that the use of vertical 1D NSs may
soon be established as a superior choice over other current techniques, with all
the further benefits that may entail.
PMID- 25130135
TI - Temporal effect of inertial cavitation with and without microbubbles on surface
deformation of agarose S gel in the presence of 1-MHz focused ultrasound.
AB - Sonoporation has the potential to deliver extraneous molecules into a target
tissue non-invasively. There have been numerous investigations of cell membrane
permeabilization induced by microbubbles, but very few studies have been carried
out to investigate sonoporation by inertial cavitation, especially from a
temporal perspective. In the present paper, we show the temporal variations in
nano/micro-pit formations following the collapse of inertial cavitation bubbles,
with and without Sonazoid(r) microbubbles. Using agarose S gel as a target
material, erosion experiments were conducted in the presence of 1-MHz focused
ultrasound applied for various exposure times, Tex (0.002-60 s). Conventional
microscopy was used to measure temporal variations in micrometer-scale pit
numbers, and atomic force microscopy utilized to detect surface roughness on a
nanometer scale. The results demonstrated that nanometer-scale erosion was
predominantly caused by Sonazoid(r) microbubbles and C4F10 gas bubbles for 0.002
s C variant on leucovorin rescue and risk of relapse in
childhood acute lymphoblastic leukemia treated with high-dose methotrexate.
AB - BACKGROUND: Recent studies suggest that SLCO1B1 c.521T > C variant decreases the
clearance of methotrexate (MTX) and elevates its plasma concentration, hence
leucovorin doses may need to be adjusted. However, high leucovorin doses may
affect the cure rate in childhood acute lymphoblastic leukemia (ALL). Hitherto
neither the appropriate dose of leucovorin in carriers of SLCO1B1 c.521T > C
variant nor the impact of SLCO1B1 polymorphism on the risk of ALL relapse has
been clarified. PROCEDURE: A double-blind and controlled study was conducted in
136 children with ALL. They were genotyped for rs4149056 single nucleotide
polymorphism into wild-type group and variant group, and received MTX at 3-5
g/m(2) . Plasma concentration MTX and its metabolite were determined by HPLC. The
toxicity of MTX, dose of leucovorin and 5-year relapse rate of ALL were recorded.
RESULTS: Compared with wild-type group, area under the concentration time curve
of MTX increased by 4.2-fold and peripheral clearance rate decreased
significantly in variant group. Patients carrying rs4149056 C allele endured a
remarkable longer time above the MTX safety threshold and suffered from a higher
frequency of toxicity, so 2.2-fold leucovorin was given. However, no association
was found between SLCO1B1 c.521T > C variant and the relapse risk in five years.
CONCLUSIONS: The SLCO1B1 c.521T > C variant was an important determinant of MTX
disposition and their carriers were exposed to increased intensity and time of
MTX. An appropriate leucovorin dose raise in variant group was beneficial to
reducing the serious toxicity. The c.521T > C variant wasn't associated with the
risk of ALL relapse.
PMID- 25130191
TI - Investigation of the effects of some phenolic compounds on the activities of
glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase from human
erythrocytes.
AB - Polyphenols are the important compounds that have various bioactivities. They
constitute vital active agents of not only daily diet but also natural medicines
that are used traditionally. It is generally considered that they are safe
because they are natural. In some conducted studies, different negative effects
of these compounds were mentioned. Twelve phenolic compounds have been assayed to
determine the effect of inhibition on glucose-6-phosphate dehydrogenase (G6PD)
and 6-phosphogluconate dehydrogenase (6PGD) enzymes activity. For in vitro
studies, the enzymes were purified from human erythrocytes using 2',5'-ADP
Sepharose 4B affinity chromatography. Naringenin, caffeic acid, ellagic acid,
ferulic acid, and sinapic acid against two enzymes, hesperidin and polydatin,
only on G6PD activity and chrysin solely against 6PGD showed inhibitory effect.
Chlorogenic acid, p-coumaric acid, and syringic acid did not exhibit an effect on
the activity of the two enzymes.
PMID- 25130194
TI - A pilot study to develop an objective clinical score for canine otitis externa.
AB - BACKGROUND: The lack of an accepted clinical scoring system in canine otitis
externa makes it difficult to compare clinical trials. HYPOTHESIS/OBJECTIVES: To
develop a score that is clinically relevant, reliable and sensitive to change.
ANIMALS: Client-owned healthy dogs (n = 55) and dogs with otitis externa (n =
60). METHODS: We compared 0-3 and 0-5 assessments of erythema, oedema/swelling,
erosion/ulceration, exudate and pain of the ear canals with a reference 0-2
scale. Additional data included odour, pruritus scores, tympanic membrane
condition, treatment outcome and neutrophil, bacterial and Malassezia counts.
RESULTS: There were no significant differences between the vertical and
horizontal canal scores (correlation coefficients >0.93). Correlation
coefficients for the 0-3 and 0-5 scales were also >0.9 for all parameters, but
the 0-2 scale was more variable. Pain and pruritus did not correlate well with
the lesion scores and were associated with suppurative and erythroceruminous
otitis, respectively. Neutrophil and microbial counts were variable and could not
be used to generate cut-off values to differentiate healthy and affected ears or
determine the response to therapy. Total scores >=4 differentiated affected from
healthy ears with 91.1% sensitivity and 100% specificity; scores <=3 were 100%
sensitive and 91.9% specific for clinical success. The intra- and interobserver
reliability was high (intraclass correlation coefficients >0.95 and Cohen's kappa
coefficients >0.65). CONCLUSIONS AND CLINICAL IMPORTANCE: This pilot study showed
that the 0-3 Otitis Index Score (OTIS3) for erythema, oedema/swelling,
erosion/ulceration and exudate is suitable for further validation by a larger
group of clinicians.
PMID- 25130192
TI - Chronic activity-based therapy does not improve body composition, insulin-like
growth factor-I, adiponectin, or myostatin in persons with spinal cord injury.
AB - Spinal cord injury (SCI) induces dramatic changes in body composition including
reductions in fat-free mass (FFM) and increases in fat mass (FM). OBJECTIVE: To
examine changes in body composition in response to chronic activity-based therapy
(ABT) in persons with SCI. DESIGN: Longitudinal exercise intervention. METHODS:
Seventeen men and women with SCI (mean age=36.1+/-11.5 years) completed 6 months
of supervised ABT consisting of load bearing, resistance training, locomotor
training, and functional electrical stimulation. At baseline and after 3 and 6
months of ABT, body weight, body fat, and FFM were assessed using dual-energy X
ray absorptiometry, and fasting blood samples were obtained to assess changes in
insulin-like growth factor-I (IGF-I), adiponectin, and myostatin. RESULTS: Across
all subjects, there was no change (P>0.05) in body weight, percent body fat, or
FFM of the leg, arm, or trunk, whereas whole-body FFM declined (P=0.02, 50.4+/
8.4 to 49.2+/-7.4 kg). No changes (P=0.21-0.41) were demonstrated in IGF-I,
adiponectin, or myostatin during the study. CONCLUSIONS: Chronic ABT focusing on
the lower extremity does not slow muscle atrophy or alter body fat, body mass, or
regional depots of FFM in persons with SCI. Further, it does not induce
beneficial changes in adiponectin, myostatin, or IGF-I. Alternative exercise
based therapies are needed in SCI to reverse muscle atrophy and minimize the
onset of related health risks.
PMID- 25130193
TI - Polymorphisms in melanoma differentiation-associated gene 5 link protein function
to clearance of hepatitis C virus.
AB - Among patients newly infected with hepatitis C virus (HCV), only 20-30% clear the
infection spontaneously. In the remaining 70% the infection persists, causing
chronic liver inflammation and disease. It is well established that polymorphisms
in host genes, especially in components of the innate immune response, contribute
to the phenomenon of spontaneous HCV clearance. Retinoic acid inducible gene-I
(RIG-I)-like helicases such as melanoma differentiation-associated gene 5 (MDA-5)
are cytoplasmic sensors of viral RNA that are critical for triggering innate
immune responses after infection with RNA viruses. We analyzed 14 nonsynonymous
single-nucleotide polymorphisms in RIG-I-like helicase-pathway-genes comparing
European patients who spontaneously cleared HCV (n = 285) or had persistent
infection (n = 509). We found that polymorphic haplotypes in the MDA-5 gene IFIH1
encoding histidine at position 843 and threonine at position 946 strongly
correlate with the resolution of HCV infection (odds ratio [OR]: 16.23; 95%
confidence interval [CI]: 3.67-71.87; P = 1.1 * 10(-6) ). Overexpression of MDA-5
genetic variants in HEK 293 cells and in a tissue culture model of HCV infection
revealed that the histidine 843/threonine 946 variant leads to increased baseline
and ligand-induced expression of interferon-induced genes and confers an
increased ability to suppress HCV replication. CONCLUSION: These data suggest
that MDA-5 plays a significant role in the defense against HCV and that
polymorphisms in MDA-5 can influence the outcome of HCV infection.
PMID- 25130195
TI - Detection of Toxoplasma gondii DNA in fresh and frozen semen from rams in Brazil.
AB - The aim of this study was to estimate the prevalence of genomic DNA of Toxoplasma
gondii in semen samples from commercial rams in artificial insemination centres
in Brazil, as well as in fresh semen from rams in the northeast of Brazil. In
total, 108 semen samples were obtained from artificial insemination centres, and
genomic DNA of T. gondii was detected in 24 of 108 (22.2%). The prevalence of
antibodies anti-Toxoplasma gondii among sheep on rural properties was 9.2%
(10/109), and 100% of the semen samples of these animals were positive in the PCR
for T. gondii DNA. The molecular identity was confirmed through sequencing, which
indicated 99.9% similarity with the T. gondii DNA sequences stored in the
GenBank. This study reports the first occurrence of T. gondii DNA in the semen of
rams, which came from artificial insemination centres in Brazil, as well as the
occurrence of T. gondii DNA in the fresh semen of naturally infected rams in the
northeast of Brazil.
PMID- 25130196
TI - Islet xenotransplantation: what is the optimal age of the islet-source pig?
AB - BACKGROUND: The need for pig islet xenotransplantation in patients with type 1
diabetes is compelling; however, the ideal age at which islets should be isolated
from the donor pig remains uncertain. Pig islet transplantation in primates, as a
valuable pre-clinical model, has been explored using adult, neonatal, fetal pig
islets, and also pancreatic primordia from pig embryos as beta cell donors.
Neonatal pig islets have some advantages over adult and fetal islets, but the
optimal age within the first month of life at which neonatal islets should be
isolated and transplanted is as yet unclear. METHODS: In an attempt to answer
this question, we carried out a literature search, but limited the search
primarily to evidence in the clinically-relevant pig-to-non-human primate model.
RESULTS: We identified surprisingly few studies in this model directed to this
topic. Even in pig-to-rodent models, there were few definitive data. CONCLUSION:
From the few data available to us, we conclude that pancreatectomy and islet
isolation from neonatal pigs may have advantages over adult pigs and that
isolation during the first week of life may have minor advantages over later
weeks.
PMID- 25130197
TI - Effects of exposure to mixed volatile organic compounds on the neurobehavioral
test performance in a cross-sectional study of US adults.
AB - While the environmental exposure to multiple volatile organic compounds (VOCs) is
ubiquitous, its neurobehavioral effects are not well understood. We assessed the
associations between short-term exposure to VOC mixtures and neurobehavioral test
performances on 497 participants in the Third National Health and Nutrition
Examination Survey, using quantile and ordinary least squares regression models.
We grouped 10 blood VOCs into 3 mixtures based on the principal component
analysis, where Mix1 included benzene, toluene, ethylbenzene, m-/p-xylene, o
xylene, and styrene; Mix2 included chloroform and tetrachloroethene; and Mix3
included 1,1,1-trichloroethane and 1,4-dichlorobenzene. We found a general lack
of significant adverse effects with exceptions limited to those with the worst
performance (i.e. the top 10 percent) in the simple reaction time test,
suggesting that these people were potentially more susceptible to impacts of VOC
mixtures. However, further research is needed to clarify the neurobehavioral
effects of chronic low-level exposure to VOC mixtures among the general
population.
PMID- 25130198
TI - The association of chemotherapy versus hormonal therapy and health outcomes among
patients with hormone receptor-positive, HER2-negative metastatic breast cancer:
experience from the patient perspective.
AB - This study aimed to characterize the impact of metastatic breast cancer (MBC) and
cancer treatments on health-related quality of life, treatment satisfaction, and
daily productivity from the patient perspective. This was a cross-sectional
survey of patients with MBC (USA, n = 200; EU, n = 160). Post-menopausal women
aged >=50 years with hormone receptor positive (HR+), HER2-negative (HER2-) MBC,
currently using hormonal therapy (HT) or using chemotherapy (CT) for <=1 year
were recruited. Fifty three percent (n = 191) reported CT and 47% (n = 169)
reported HT use. Adjusting for covariates, HT users reported greater health
related quality of life (p < 0.05), greater satisfaction with treatment and
better feelings about side-effects (p < 0.001). HT users reported less bother
with treatment side-effects (0-5 scale, p < 0.001) and less activity impairment
than CT users (p < 0.001). HT was associated with better patient-reported
outcomes than CT in first-line MBC management. These findings should be taken
into consideration while making treatment decisions for HR+/HER2- MBC.
PMID- 25130199
TI - Yeast synthetic biology for the production of recombinant therapeutic proteins.
AB - The production of recombinant therapeutic proteins is one of the fast-growing
areas of molecular medicine and currently plays an important role in treatment of
several diseases. Yeasts are unicellular eukaryotic microbial host cells that
offer unique advantages in producing biopharmaceutical proteins. Yeasts are
capable of robust growth on simple media, readily accommodate genetic
modifications, and incorporate typical eukaryotic post-translational
modifications. Saccharomyces cerevisiae is a traditional baker's yeast that has
been used as a major host for the production of biopharmaceuticals; however,
several nonconventional yeast species including Hansenula polymorpha, Pichia
pastoris, and Yarrowia lipolytica have gained increasing attention as alternative
hosts for the industrial production of recombinant proteins. In this review, we
address the established and emerging genetic tools and host strains suitable for
recombinant protein production in various yeast expression systems, particularly
focusing on current efforts toward synthetic biology approaches in developing
yeast cell factories for the production of therapeutic recombinant proteins.
PMID- 25130201
TI - Quantitative developmental data in a phylogenetic framework.
AB - Following the embryonic period of organogenesis, most development is allometric
growth, which is thought to produce most of the evolutionary morphological
divergence between related species. Bivariate or multivariate coefficients of
allometry are used to describe quantitative developmental data and are comparable
across taxa; as such, these coefficients are amenable to direct treatment in a
phylogenetic framework. Mapping of actual allometric coefficients onto
phylogenetic trees is supported on the basis of the evolving nature of growth
programs and the type of character (continuous) that they represent. This
procedure depicts evolutionary allometry accurately and allows for the generation
of reliable reconstructions of ancestral allometry, as shown here with a
previously published case study on rodent cranial ontogeny. Results reconstructed
the signature allometric patterns of rodents to the root of the phylogeny, which
could be traced back into a (minimum) Paleocene age. Both character and
statistical dependence need to be addressed, so this approach can be integrated
with phylogenetic comparative methods that deal with those issues. It is shown
that, in this particular sample of rodents, common ancestry explains little
allometric variation given the level of divergence present within, and
convergence between, major rodent lineages. Furthermore, all that variation is
independent of body mass. Thus, from an evolutionary perspective, allometry
appears to have a strong functional and likely adaptive basis.
PMID- 25130200
TI - Natural selection acts in opposite ways on correlated hormonal mediators of
prenatal maternal effects in a wild bird population.
AB - Maternal hormones are important mediators of prenatal maternal effects. Although
many experimental studies have demonstrated their potency in shaping offspring
phenotypes, we know remarkably little about their adaptive value. Using long-term
data on a wild collared flycatcher (Ficedula albicollis) population, we show that
natural selection acts in opposite ways on two maternally derived androgens, yolk
androstenedione (A4) and yolk testosterone (T). High yolk A4 concentrations are
associated with higher fitness, whereas high yolk T concentrations are associated
with lower fitness. Natural selection thus favours females that produce eggs with
high A4 and low T concentrations. Importantly, however, there exists a positive
(non-genetic) correlation between A4 and T, which suggests that females are
limited in their ability to reach this adaptive optimum. Thereby, these results
provide strong evidence for an adaptive value of differential maternal androgen
deposition, and a mechanistic explanation for the maintenance of variation in
maternal investment in the wild.
PMID- 25130202
TI - Protective effects of myricitrin against osteoporosis via reducing reactive
oxygen species and bone-resorbing cytokines.
AB - Oxidative stress is a crucial pathogenic factor in the development of
osteoporosis. Myricitrin, isolated from Myrica cerifera, is a potent antioxidant.
We hypothesized that myricitrin possessed protective effects against osteoporosis
by partially reducing reactive oxygen species (ROS) and bone-resorbing cytokines
in osteoblastic MC3T3-E1 cells and human bone marrow stromal cells (hBMSCs). We
investigated myricitrin on osteogenic differentiation under oxidative stress.
Hydrogen peroxide (H2O2) was used to establish an oxidative cell injury model.
Our results revealed that myricitrin significantly improved some osteogenic
markers in these cells. Myricitrin decreased lipid production and reduced
peroxisome proliferator-activated receptor gamma-2 (PPARgamma2) expression in
hBMSCs. Moreover, myricitrin reduced the expression of receptor activator of
nuclear factor kappa-B ligand (RANKL) and IL-6 and partially suppressed ROS
production. In vivo, we established a murine ovariectomized (OVX) osteoporosis
model. Our results demonstrated that myricitrin supplementation reduced serum
malondialdehyde (MDA) activity and increased reduced glutathione (GSH) activity.
Importantly, it ameliorated the micro-architecture of trabecular bones in the 4th
lumbar vertebrae (L4) and distal femur. Taken together, these results indicated
that the protective effects of myricitrin against osteoporosis are linked to a
reduction in ROS and bone-resorbing cytokines, suggesting that myricitrin may be
useful in bone metabolism diseases, particularly osteoporosis.
PMID- 25130203
TI - Clinical risk factors for central lymph node metastasis in papillary thyroid
carcinoma: a systematic review and meta-analysis.
AB - BACKGROUND: Prophylactic central lymph node dissection (CLND) in clinically node
negative patients remains controversial, and predictive factors for central lymph
node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) are not
well defined. Herein, we conducted a systematic review to quantify the
clinicopathologic factors predictive for CLNM in patients with PTC. METHODS: A
systematic search of electronic databases (PubMed, Embase, Cochrane CENTRAL,
Scopus and Wanfang Database) for studies published until July 2014 was performed.
Cohort, case-control studies and randomized controlled trials that examined
clinical risk factors of CLNM were included. RESULTS: Twenty-five studies (4
prospective and 21 retrospective studies) involving 7,719 patients met final
inclusion criteria. From the pooled analyses, male gender (OR 1.93, 95% CI 1.40
to 2.64), tumour multifocality (OR 1.93, 95% CI 1.62 to 2.30), tumour size >0.5
cm (OR 3.48, 95% CI 2.24 to 5.41), capsular invasion (OR 1.91, 95% CI 1.36 to
2.67), extrathyroidal extension (OR 2.42, 95% CI 1.58 to 3.71), lymphovascular
invasion (OR 13.29, 95% CI 5.61 to 31.48) and lateral lymph node metastasis (OR
14.33, 95% CI 5.34 to 38.50) were significantly associated with increased risk of
CLNM, while age >45 years (OR 0.65, 95% CI 0.51 to 0.83) and lymphocytic
thyroiditis (OR 0.70, 95% CI 0.53 to 0.92) resulted in decreased risk of CLNM.
Bilaterality and tumour location were not significantly associated with CLNM
development (all P > 0.05). CONCLUSIONS: Our analysis identified several
clinicopathologic factors associated with CLNM. These findings may guide the
necessity and extent of prophylactic CLND and ultimately improve the outcomes of
patients with PTC.
PMID- 25130204
TI - Direct observation of coherent oscillations in solution due to microheterogeneous
environment.
AB - We report, for the first time, direct observation of coherent oscillations in the
ground-state of IR775 dye due to microheterogeneous environment. Using ultrafast
near-infrared degenerate pump-probe technique centered at 800 nm, we present the
dynamics of IR775 in a binary mixture of methanol and chloroform at ultra-short
time resolution of 30 fs. The dynamics of the dye in binary mixtures, in a time
scale of a few fs to ~740 ps, strongly varies as a function of solvent
composition (volume fraction). Multi-oscillation behavior of the coherent
vibration was observed, which increased with decreasing percentage of methanol in
the dye mixture. Maximum number of damped oscillations were observed in 20%
methanol. The observed vibrational wavepacket motion in the ground-state is
periodic in nature. We needed two cosine functions to fit the coherent
oscillation data as two different solvents were used. Dynamics of the dye
molecule in binary mixtures can be explained by wavepacket motion in the ground
potential energy surface. More is the confinement of the dye molecule in binary
mixtures, more is the number of damped oscillations. The vibrational cooling
time, tau2, increases with increase in the confinement of the system. The
observed wavepacket oscillations in ground-state dynamics continued until 1.6 ps.
PMID- 25130205
TI - Prospective comparison treatment of 595-nm pulsed-dye lasers for virgin port-wine
stain.
AB - BACKGROUND: Vbeam((r)) and Cynergy((r)) are 595-nm pulsed-dye laser (PDL)
equipment options, both extensively used in the clinical treatment of port-wine
stains (PWS). However, there has been no study conducted of the differences in
PWS therapeutic outcomes across both devices. OBJECTIVES: To compare the efficacy
and safety of Vbeam and Cynergy equipment in the treatment of PWS. METHODS:
Twenty-two patients with PWS were included in this study and were treated with
both Vbeam and Cynergy. Patients underwent three treatment sessions. Treatment
parameters used were as follows: (i) Cynergy((r)) , Cynosure Corp., 595-nm
wavelength, radiant exposure of 11 J cm(-2) , 2-ms pulse duration, 7-mm spot
size, cold-air cooling system of level 3. (ii) Vbeam((r)) , Candela Corp., 595-nm
wavelength, radiant exposure of 11 J cm(-2) , 1.5-ms pulse duration, 7-mm spot
size, cryogen spray cooling (30 ms of cooling with a 20-ms delay). Clinical
efficacy outcomes were evaluated by chromameter and visual assessment 2 months
post-treatment. RESULTS: All patients were treated by both Vbeam and Cynergy on
adjacent sites. Chromameter evaluation showed that the average blanching rate was
21.24% for Cynergy sites and 36.42% for Vbeam sites. This difference was
statistically significant (P = 0.05), which suggests that PWS respond better to
Vbeam than to Cynergy at the settings used in this study. No patients developed
scarring or permanent pigmentation change. CONCLUSIONS: Compared with Cynergy,
Vbeam may be more effective in the treatment of PWS. Despite using supposedly
equivalent fluences in 595-nm PDLs, equivalent clinical results cannot be
guaranteed.
PMID- 25130207
TI - Developing Clinical Research Relationship: Views from Within.
AB - The nature of the relationship between clinical investigator and research
participant continues to be contested. The related discussions have largely
focused on the doctor-researcher dichotomy thought to permeate the work of a
clinical investigator with research participants, whom in turn occupy two
corresponding roles: patient and subject. This paper contributes to current
debates on the topic by providing a voice to research participants, whose
perspectives have been largely invisible. It draws on 42 in-depth interviews
conducted in Ghana and South Africa with respondents at different stages of
involvement in clinical research, ranging from no experience in clinical research
to enrollment in several clinical trials. The perspectives of all respondents
were largely congruent and rooted in the common view that clinical research
contributed to the improvement of local health. They went beyond the
researcher/participant versus doctor/patient dichotomy, long established in
research ethics, and preferred to view participants and investigators as partners
working together to find ways to address local health needs. The
conceptualization of investigator-participant relations as a partnership
reinforced expectations of care, transparency and accountability, which were
viewed as necessary expressions of mutuality and respect within equal
collaborations. It is important to engage with these views in order to avoid
antagonizing societal expectations and to build up long-term public trust,
crucial for the continuous operation of clinical research.
PMID- 25130206
TI - Parent-of-origin growth effects and the evolution of hybrid inviability in dwarf
hamsters.
AB - Mammalian hybrids often show abnormal growth, indicating that developmental
inviability may play an important role in mammalian speciation. Yet, it is
unclear if this recurrent phenotype reflects a common genetic basis. Here, we
describe extreme parent-of-origin-dependent growth in hybrids from crosses
between two species of dwarf hamsters, Phodopus campbelli and Phodopus sungorus.
One cross type resulted in massive placental and embryonic overgrowth, severe
developmental defects, and maternal death. Embryos from the reciprocal cross were
viable and normal sized, but adult hybrid males were relatively small. These
effects are strikingly similar to patterns from several other mammalian hybrids.
Using comparative sequence data from dwarf hamsters and several other hybridizing
mammals, we argue that extreme hybrid growth can contribute to reproductive
isolation during the early stages of species divergence. Next, we tested if
abnormal growth in hybrid hamsters was associated with disrupted genomic
imprinting. We found no association between imprinting status at several
candidate genes and hybrid growth, though two interacting genes involved in
embryonic growth did show reduced expression in overgrown hybrids. Collectively,
our study indicates that growth-related hybrid inviability may play an important
role in mammalian speciation but that the genetic underpinnings of these
phenotypes remain unresolved.
PMID- 25130209
TI - Participant comprehension of research for which they volunteer: a systematic
review.
AB - PURPOSE: Evidence indicates that research participants often do not fully
understand the studies for which they have volunteered. The aim of this
systematic review was to examine the relationship between the process of
obtaining informed consent for research and participant comprehension and
satisfaction with the research. DESIGN: Systematic review of published research
on informed consent and participant comprehension of research for which they
volunteer using the Preferred Reporting Items for Systematic Review and Meta
Analysis (PRISMA) Statement as a guide. METHODS: PubMed, Cumulative Index for
Nursing and Allied Health Literature, Cochrane Central Register of Controlled
Trails, and Cochrane Database of Systematic Reviews were used to search the
literature for studies meeting the following inclusion criteria: (a) published
between January 1, 2006, and December 31, 2013, (b) interventional or descriptive
quantitative design, (c) published in a peer-reviewed journal, (d) written in
English, and (e) assessed participant comprehension or satisfaction with the
research process. Studies were assessed for quality using seven indicators:
sampling method, use of controls or comparison groups, response rate, description
of intervention, description of outcome, statistical method, and health literacy
assessment. FINDINGS: Of 176 studies identified, 27 met inclusion criteria: 13
(48%) were randomized interventional designs and 14 (52%) were descriptive. Three
categories of studies included projects assessing (a) enhanced consent process or
form, (b) multimedia methods, and (c) education to improve participant
understanding. Most (78%) used investigator-developed tools to assess participant
comprehension, did not assess participant health literacy (74%), or did not
assess the readability level of the consent form (89%). Researchers found
participants lacked basic understanding of research elements: randomization,
placebo, risks, and therapeutic misconception. CONCLUSIONS: Findings indicate (a)
inconsistent assessment of participant reading or health literacy level, (b)
measurement variation associated with use of nonstandardized tools, and (c)
continued therapeutic misconception and lack of understanding among research
participants of randomization, placebo, benefit, and risk. While the Agency for
Healthcare and Quality and National Quality Forum have published informed consent
and authorization toolkits, previously published validated tools are
underutilized. CLINICAL RELEVANCE: Informed consent requires the assessment of
health literacy, reading level, and comprehension of research participants using
validated assessment tools and methods.
PMID- 25130210
TI - Maternal unresponsiveness and child disruptive problems: the interplay of
uninhibited temperament and dopamine transporter genes.
AB - This study examined how and why dopamine transporter (DAT1) susceptibility
alleles moderate the relation between maternal unresponsiveness and young
children's behavior problems in a disadvantaged, predominantly minority sample of
201 two-year-old children and their mothers. Using a multimethod, multisource
design, the findings indicated that a genetic composite of DAT1 susceptibility
alleles (rs27072, rs40184) potentiated associations between maternal unresponsive
caregiving and increases in children's behavior problems 2 years later. Moderator
mediated-moderation analyses further revealed that the DAT1 diathesis was more
proximally mediated by the potentiating effects of children's uninhibited
temperament in the pathway between maternal unresponsiveness and disruptive
behavior problems. Results are interpreted in the context of supporting and
advancing the biosocial developmental model (Beauchaine & Gatzke-Kopp, 2012).
PMID- 25130208
TI - Assessing the effectiveness of the 'Incredible Years((r)) parent training' to
parents of young children with ADHD symptoms - a preliminary report.
AB - This study examined the effectiveness of an evidence-based parent training
program in a real-world Scandinavian setting. Parents of 36 young children with
or at risk of Attention Deficit Hyperactive Disorder (ADHD) self-referred to
participate in the Incredible Years((r)) Parent Training Program (IYPT) through a
Danish early intervention clinic. Using a benchmarking approach, we compared self
report data with data from a recent efficacy study. Eight out of nine outcome
measures showed comparable or higher magnitude of effect from pretest to
posttest. Effects were maintained or improved across six months. The methodology
of this study exemplifies a rigorous but feasible approach to assessing
effectiveness when evidence-based US protocols are transferred into the existing
Scandinavian service delivery. Findings suggest that IYPT can be implemented
successfully as an easy-access early intervention to families of children with or
at risk of ADHD.
PMID- 25130211
TI - Persistent inflammation and its relationship to leptin and insulin in phases of
bipolar disorder from acute depression to full remission.
AB - OBJECTIVE: A proinflammatory phase with various immunomodulatory mechanisms has
been noted in bipolar mania and major depression. Weight gain and increased
production of leptin may be associated with immunomodulation and insulin
resistance in bipolar disorder. However, immunomodulation and its linkage with
leptin and insulin in the depressive episode of bipolar disorder remain unclear.
We investigated alterations in inflammatory markers and their relationship with
leptin and insulin levels in patients with phases of bipolar disorder from acute
depression to full remission. METHODS: Thirty-two physically healthy bipolar I
depressed patients aged <45 years and age- and sex-matched healthy controls
participated in this study. We measured their circulating levels of leptin,
insulin, high-sensitivity C-reactive protein (hs-CRP), soluble interleukin-2
receptor (sIL-2R), soluble interleukin-6 receptor (sIL-6R), soluble tumor
necrosis factor receptor 1 (sTNF-R1), and interleukin-1 receptor antagonist (IL
1Ra) in three phases, i.e., acute depression, subsequent partial remission, and
full remission. RESULTS: In acute depression, subsequent partial remission, and
full remission, patients with bipolar disorder had significantly higher mean
levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R compared with control subjects. The
IL-1Ra and sTNF-R1 levels in various affective phases were significantly
correlated to body mass index, leptin level, circulating lipids, and medication
status. The sIL-2R levels in the three affective phases were all independent of
other inflammatory markers and clinical and laboratory variables. Patients showed
no alteration of sIL-6R levels through the depressive episode. CONCLUSIONS:
Patients with bipolar disorder in depressive episodes may exhibit persistent
inflammation with elevated levels of hs-CRP, IL-1Ra, sTNF-R1, and sIL-2R but not
sIL-6R from the acute phases to full remission. Only sIL-2R production seems to
be tightly linked with the pathophysiology of bipolar depression and is
independent of insulin and leptin levels.
PMID- 25130213
TI - IMAGING DIAGNOSIS--ACUTE MESENTERIC ISCHEMIA ASSOCIATED WITH HYPERTROPHIC
CARDIOMYOPATHY IN A CAT.
AB - A middle-aged cat was presented with vomiting, diarrhea, and pelvic limb paresis.
Radiography showed cardiomegaly, interstitial pulmonary infiltration, distended
intestinal loops, and portal venous gas. Hypertrophic cardiomyopathy (HCM) was
confirmed. On CT, thrombi were identified at the abdominal aorta, superior
mesenteric artery, bilateral renal arteries, and cauda vena cava at the level of
the iliac vein bifurcation. Dilated and gas-filled loops of bowel with a "paper
thin wall" were observed on CT images and were considered indicative of necrotic
bowel. This case report describes the CT findings of acute mesenteric ischemia
associated with HCM in a cat.
PMID- 25130212
TI - A comprehensive analysis of the cellular and EBV-specific microRNAome in primary
CNS PTLD identifies different patterns among EBV-associated tumors.
AB - Primary central nervous system (pCNS) posttransplant lymphoproliferative disorder
(PTLD) is a complication of solid organ transplantation characterized by poor
outcome. In contrast to systemic PTLD, Epstein-Barr virus (EBV)-association of
pCNS PTLD is almost universal, yet viral and cellular data are limited. To
identify differences in the pattern of EBV-association of pCNS and systemic PTLD,
we analyzed the expression of latent and lytic EBV transcripts and the viral and
cellular microRNAome in nine pCNS (eight EBV-associated) and in 16 systemic PTLD
samples (eight EBV-associated). Notably although 15/16 EBV-associated samples
exhibited a viral type III latency pattern, lytic transcripts were also strongly
expressed. Members of the ebv-miR-BHRF1 and ebv-miR-BART clusters were expressed
in virtually all EBV-associated PTLD samples. There were 28 cellular microRNAs
differentially expressed between systemic and pCNS PTLD. pCNS PTLD expressed
lower hsa-miR-199a-5p/3p and hsa-miR-143/145 (implicated in nuclear factor kappa
beta and c-myc signaling) as compared to systemic PTLD. Unsupervised
nonhierarchical clustering of the viral and cellular microRNAome distinguished
non-EBV-associated from EBV-associated samples and identified a separate group of
EBV-associated pCNS PTLD that displayed reduced levels of B cell lymphoma
associated oncomiRs such as hsa-miR-155, -21, -221 and the hsa-miR-17-92 cluster.
EBV has a major impact on viral and cellular microRNA expression in EBV
associated pCNS PTLD.
PMID- 25130215
TI - Plasmon modes in graphene: status and prospect.
AB - Plasmons in graphene have unusual properties and offer promising prospects for
plasmonic applications covering a wide frequency range, ranging from terahertz up
to the visible. Plasmon modes have been recently studied in both free-standing
and supported graphene. Here, we review plasmons in graphene with particular
emphasis on plasmonic excitations in epitaxial graphene and on the influence of
the underlying substrate on the screening processes. Although the theoretical
comprehension of plasmons in supported graphene is still incomplete, several
experimental results provide clues regarding the nature of plasmonic excitations
in graphene on metals and semiconductors. Plasmon in graphene can be tuned by
chemical doping and gating potentials. We show through selected examples that the
adsorbates can be used to tune the plasmon frequency, while the intercalation of
chemical species allows the decoupling of the graphene sheet from the substrate
to recover the plasmon dispersion of pristine graphene. Finally, we also report
intriguing effects due to many-body interaction, such as the excitations
generated by electron-electron coupling (magnetoplasmons) and the composite modes
arising from the coupling of plasmons with phonons and with charge carriers.
PMID- 25130216
TI - Addressing asthma disparities using clinical decision support in the electronic
health record.
PMID- 25130217
TI - From underrepresented minority high school student to medical school faculty
member: how an outreach program changed my life.
PMID- 25130214
TI - Homotopic connectivity in drug-naive, first-episode, early-onset schizophrenia.
AB - BACKGROUND: The disconnection hypothesis of schizophrenia has been extensively
tested in adults. Recent studies have reported the presence of brain
disconnection in younger patients, adding evidence to support the
neurodevelopmental hypothesis of schizophrenia. Because of drug confounds in
chronic and medicated patients, it has been extremely challenging for researchers
to directly investigate abnormalities in the development of connectivity and
their role in the pathophysiology of schizophrenia. The present study aimed to
examine functional homotopy - a measure of interhemispheric connection - and its
relevance to clinical symptoms in first-episode drug-naive early-onset
schizophrenia (EOS) patients. METHODS: Resting-state functional magnetic
resonance imaging was performed in 26 first-episode drug-naive EOS patients (age:
14.5 +/- 1.94, 13 males) and 25 matched typically developing controls (TDCs)
(age: 14.4 +/- 2.97, 13 males). We were mainly concerned with the functional
connectivity between any pair of symmetric interhemispheric voxels (i.e.,
functional homotopy) measured by voxel-mirrored homotopic connectivity (VMHC).
RESULTS: Early-onset schizophrenia patients exhibited both global and regional
VMHC reductions in comparison with TDCs. Reduced VMHC values were observed within
the superior temporal cortex and postcentral gyrus. These interhemispheric
synchronization deficits were negatively correlated with negative symptom of the
Positive and Negative Syndrome Scale. Moreover, regions of interest analyses
based on left and right clusters of temporal cortex and postcentral gyrus
revealed abnormal heterotopic connectivity in EOS patients. CONCLUSIONS: Our
findings provide novel neurodevelopmental evidence for the disconnection
hypothesis of schizophrenia and suggest that these alterations occur early in the
course of the disease and are independent of medication status.
PMID- 25130218
TI - Ability to deliver services in Spanish: a survey of Michigan home health
agencies, 2012.
AB - The capacity of home health agencies to serve children from families with low
English proficiency is not well understood. We conducted an exploratory survey of
home health agencies in Michigan in 2012 to document whether they can provide
services in Spanish, serve children, and accept Medicaid.
PMID- 25130219
TI - Influence of education on HIV infection among pregnant women attending their
antenatal care in Sekondi-Takoradi metropolis, Ghana.
AB - This study investigated the influence of the level of education on HIV infection
among pregnant women attending antenatal care in Sekondi-Takoradi, Ghana. A cross
sectional study was conducted at four hospitals in the Sekondi-Takoradi
metropolis. The study group comprised 885 consenting pregnant women attending
antenatal care clinics. Questionnaires were administered and venous blood samples
were screened for HIV and other parameters. Multivariable logistic regression
analyses were performed to determine the association between the level of
education attained by the pregnant women and their HIV statuses. The data showed
that 9.83% (87/885) of the pregnant women were HIV seropositive while 90.17%
(798/885) were HIV seronegative. There were significant differences in mean age
(years) between the HIV seropositive women (27.45 +/- 5.5) and their HIV
seronegative (26.02 +/- 5.6) counterparts (p = .026) but the inference
disappeared after adjustment (p = .22). Multivariable logistic regression
analysis revealed that pregnant women with secondary/tertiary education were less
likely to have HIV infection compared with those with none/primary education
(adjusted OR, 0.53; 95% CI, 0.30-0.91; p = .022). Our data showed an association
with higher level of education and HIV statuses of the pregnant women. It is
imperative to encourage formal education among pregnant women in this region.
PMID- 25130220
TI - Post-traumatic stress symptoms among juvenile offenders in nigeria: implications
for holistic service provisioning in juvenile justice administration.
AB - BACKGROUND: There is hardly any study examining exposure to traumatic events and
post-traumatic stress disorder (PTSD) among juvenile justice populations in
Nigeria or any part of sub-Saharan Africa. METHOD: We examined the prevalence and
trauma determinants of PTSD among a cohort of juvenile justice inmates in
Nigeria, compared with a cohort of school-going adolescents. RESULTS: Ninety
percent (90%) of the juvenile justice inmates reported exposure to at least one
lifetime traumatic event with higher mean incident events, compared with 60%
among the comparison group (p=.001). Juvenile justice inmates had significantly
higher prevalence rate of current and lifetime PTSD than the comparison group
(current: 5.8% vs. 1.4%; lifetime: 9.7% vs. 2.8%, p<.05). Mean incident traumatic
event was statistically significantly higher among juvenile justice inmates who
had PTSD. CONCLUSION: Posttraumatic stress symptoms are common among adolescents
coming in contact with the juvenile justice system. Implications for holistic
service provisioning in juvenile justice administration are discussed.
PMID- 25130221
TI - Gendered inequalities within Ghana's National Health Insurance Scheme: are poor
women being penalized with a late renewal policy?
AB - This article addresses the implications of the mandatory delay in coverage for
individuals residing in the Upper West Region (UWR) of Ghana who have dropped out
of the National Health Insurance Scheme (NHIS) but later attempt to reenroll.
Using data collected in 2011 in Ghana's UWR, we use a negative log-log model
(n=1,584) to compare those who remain enrolled in the scheme with those who have
dropped out. Women with unreliable incomes, who reported being food-insecure and
those living with young children were more likely to drop out (OR range: 1.22
1.79, p<.05). Men, in contrast, were 50% more likely to drop out of the NHIS for
being unsatisfied with services provided (OR range: 1.25-1.62, p<.01). Contrary
to the original mandate of the NHIS, our study reveals clear gender differences
in the factors contributing to dropouts, pointing to a bias in the impact of the
block-out policy that is penalizing women for being poor.
PMID- 25130222
TI - End-of-life treatment preference among low-income older adults: a race/ethnicity
comparison study.
AB - INTRODUCTION: Racial/ethnic minority older adults in low-income status might be
at a greater risk than others of developing chronic illness. We sought to examine
the effects of race/ethnicity on end-of-life (EOL) treatment preference among low
income older adults. METHODS: A cross-sectional study surveyed 256 low-income
older adults (90 Whites, 82 Hispanics, 84 Blacks) in a California city. RESULTS:
Hierarchical multiple regression results showed that participants with greater
religiosity (p < .01) or more frequent doctors' visits (p < .05) had greater
preference for life-sustaining treatments during the final phase of life.
Conversely, those with greater comfort about death (p < .01) or a belief that
life and death are predestined (p < .05) preferred life-sustaining treatments
less often. Race/ethnicity had no significant relationship with EOL treatment
preference after accounting for other factors. CONCLUSION: Race/ethnicity
encompasses multiple life contexts. Understanding the influences of both cultural
beliefs and individual circumstances on EOL treatment preference is imperative.
PMID- 25130223
TI - Unmet medical care and sexual health counseling needs-: a cross-sectional study
among university students in Uganda.
AB - In 2010, unmet medical care and sexual health counseling needs were assessed
among students at a Ugandan University. Unmet medical care need was associated
with poor mental health, experience of sexual coercion, and poor self-rated
health. Unmet sexual health counseling need was significantly associated with
being female, coming from an urban area, low social participation, poor mental
health status, experience of sexual coercion, poor self-rated health,
inconsistent condom use, and having multiple sexual partners. Gender differences,
poor mental health, sexual coercion, poor self-rated health, and risky sexual
behavior must be considered when designing intervention models to reduce unmet
health care needs among young people in this setting.
PMID- 25130225
TI - Definition and management of hypertension among Haitian immigrants: a qualitative
study.
AB - Hypertension is a major health concern among Haitian immigrants, one of the
largest Caribbean immigrant groups in the United States. Yet, little is known
about how Hatian immigrants define and manage hypertension. For this qualitative
study, face-to-face semi-structured interviews were conducted with 31 Haitian
immigrants in Miami Dade County, Florida. Results indicated that most Haitian
immigrants used the Haitian Creole word tansyon to represent hypertension.
Tansyon was considered as either a normal condition of the human body or a maladi
(illness). Both traditional biomedical and alternative approaches were used to
manage hypertension. The findings show that how Haitian immigrants defined
hypertension shaped their beliefs about its occurrence and the resulting
management strategies used. Those who believed tansyon was a normal body
condition did not take any management measures. Awareness and understanding of
Haitian immigrants' beliefs about and approaches to hypertension management can
enhance culturally sensitive care and improve health outcomes.
PMID- 25130224
TI - Barriers to HIV Testing in Black Immigrants to the U.S.
AB - BACKGROUND: Late HIV testing is common among immigrants from sub Saharan Africa
and the Caribbean. Since 2010, HIV testing is no longer a required component of
immigrant screening examinations or mandatory for immigrants seeking long term
residence in the US. Thus, barriers to HIV testing must be addressed. METHODS:
Five hundred and fifty-five (555) immigrants completed a barriers-to-HIV testing
scale. Univariate and multivariate linear regression were performed to examine
predictors of barriers. RESULTS: In multivariate analysis, primary language other
than English (beta=2.9, p=.04), lower education (beta=5.8, p=.03), low income [=
below $20K/year] (beta=4.6, p=.01), no regular provider (beta=5.2, p=.002) and
recent immigration (beta=5.7, p=.0008) were independently associated with greater
barriers. Barriers due to health care access, privacy, fatalism, and anticipated
stigma were greater for recent versus longer term immigrants. DISCUSSION:
Immigrants from sub-Saharan Africa and the Caribbean face significant barriers to
HIV testing. Interventions to improve access and timely entry into care are
needed.
PMID- 25130227
TI - Family gym: a model to promote physical activity for families with young
children.
AB - This report describes Family Gym, a family-centered model that (1) provides free
access to physical activity for low-income families in the inner city; (2)
targets young children (3-8 years) and their families; (3) engages families
together in physical activity; and (4) stimulates social interaction among
families.
PMID- 25130226
TI - Promoting Chinese-speaking primary care physicians' communication with immigrant
patients about colorectal cancer screening: a cluster randomized trial design.
AB - Chinese Americans underutilize colorectal cancer screening. This study evaluated
a physician-based intervention guided by social cognitive theory (SCT) to inform
future research involving minority physicians and patients. Twenty-five Chinese
speaking primary care physicians were randomized into intervention or usual care
arms. The intervention included two 45-minute in-office training sessions paired
with a dual-language communication guide detailing strategies in addressing
Chinese patients' screening barriers. Physicians' feedback on the intervention,
their performance data during training, and pre-post intervention survey data
were collected and analyzed. Most physicians (~85%) liked the intervention
materials but ~84% spent less than 20 minutes reading the guide and only 46%
found the length of time for in-office training acceptable. Despite this, the
intervention increased physicians' perceived communication self-efficacy with
patients (p<.01). This study demonstrated the feasibility of enrolling and
intervening with minority physicians. Time constraints in primary care practice
should be considered in the design and implementation of interventions.
PMID- 25130228
TI - Patching the safety net: establishing a free specialty care clinic in an academic
medical center.
AB - We describe the collaboration between an academic medical center and a free
primary care clinic that provides multi-specialty services to indigent community
members. Complementary components of both institutions have engendered a system
in which they broaden the array of available services, providing a prototype for
other institutions to consider.
PMID- 25130229
TI - Exploring Protective factors among homeless youth: the role of natural mentors.
AB - This study explored the presence and characteristics of natural mentors among 197
homeless youth and the association between natural mentoring relationships and
youth functioning. Few studies have explored protective factors in the lives of
homeless youth and how these may buffer against poor health outcomes.
Relationships with natural mentors have been shown to have protective effects on
adolescent functioning among the general adolescent population, and, thus,
warrant further investigation with homeless youth. Results from this study
revealed that 73.6% of homeless youth have natural mentoring relationships, split
between kin and non-kin relationships. Having a natural mentor was associated
with higher satisfaction with social support and fewer risky sexual behaviors.
Findings suggest that natural mentors may play a protective role in the lives of
homeless youth and should be considered an important source of social support
that may enhance youth resilience.
PMID- 25130230
TI - Health outcomes and retention in care following release from prison for patients
of an urban post-incarceration transitions clinic.
AB - Chronic health conditions are overrepresented among prisoners who often face
barriers to medical care following release. Transitions clinics seek to provide
timely access to medical care following release. This retrospective cohort study
investigated care delivery and health outcomes for recently released prisoners
receiving care at the Bronx Transitions Clinic. Among 135 recently released
prisoners, median time from release to initial medical visit was 10 days (IQ
Range: 5-31). Six-month retention in care was high for HIV-infection (86%), but
lower for opioid dependence (33%), hypertension (45%) and diabetes (43%). At six
months, 54% of HIV-patients had a suppressed viral load, but fewer buprenorphine
treated patients reduced opioid use (19%), and fewer hypertensive and diabetic
patients reached respective blood pressure (35%) and hemoglobin A1c (14%) goals.
Access to medical care is necessary but not sufficient to control chronic health
conditions. Additional interventions are necessary for formerly incarcerated
people to achieve optimal health outcomes.
PMID- 25130231
TI - Do our patients have enough to eat?: Food insecurity among urban low-income
cancer patients.
AB - This study assessed the prevalence and predictors of food insecurity among a
cohort of underserved oncology patients at New York City cancer clinics. A
demographic survey and the U.S. Household Food Security Survey Module were
administered. A multivariate General Linear Model Analysis of Covariance was used
to evaluate predictors of food insecurity. Four hundred and four (404) completed
the surveys. Nearly one-fifth (18%) had very low, 38% low, 17% marginal, and 27%
high food security. The Analysis of Covariance was statistically significant
(F[7, 370] = 19.08; p < .0001; R-Square = 0.26). Younger age, Spanish language,
poor health care access, and having less money for food since beginning cancer
treatment were significantly associated with greater food insecurity. This cohort
of underserved cancer patients had rates of food insecurity nearly five times
those of the state average. More research is needed to understand better the
causes and impact of food insecurity among cancer and chronic disease patients.
PMID- 25130232
TI - Adverse childhood events: incarceration of household members and health-related
quality of life in adulthood.
AB - BACKGROUND: Incarceration of a household member has been associated with adverse
outcomes for child well-being. METHODS: We assessed the association between
childhood exposure to the incarceration of a household member and adult health
related quality of life (HRQOL) in the 2009/2010 Behavioral Risk Factor
Surveillance System controlling for age, race/ethnicity, education, and
additional adverse childhood experiences. RESULTS: Adults who lived in childhood
with an incarcerated household member had higher risk of poor HRQOL compared with
adults who had not (adjusted relative risk [ARR] 1.18; 95% CI 1.07, 1.31). Among
Black adults the association was strongest with the physical health component of
HRQOL (ARR 1.58 [95% CI 1.18, 2.12]); among White adults, the association was
strongest with the mental health component of HRQOL (ARR 1.29, [95% CI 1.07
1.54]). CONCLUSIONS: Living with an incarcerated household member during
childhood is associated with higher risk of poor HRQOL during adulthood,
suggesting that the collateral damages of incarceration for children are long
term.
PMID- 25130233
TI - "The stress will kill you": prisoner reentry as experienced by family members and
the urgent need for support services.
AB - The role of incarceration and community reentry after incarceration has been
studied extensively for individual and community health; however, little
attention has been given to the experiences of individuals who provide support to
those in reentry. Through a community-academic partnership, seven focus groups
were conducted with 39 individuals supporting a family member in reentry in the
summer of 2012. The primary objectives of the focus groups were to explore
community experiences and perspectives regarding providing support during a
family member's reentry from a period of incarceration and any desired support
for themselves during this time. Five themes emerged under a metatheme of stress,
indicating that family members experience acute stress as a result of family
reentry that adds to the chronic stress they already endure. Programs that
acknowledge the difficult role of family members as supporters during an
individual's reentry and provide support to them are desperately needed.
PMID- 25130234
TI - Psychiatric disorders, high-risk behaviors, and chronicity of episodes among
predominantly African American homeless Chicago youth.
AB - OBJECTIVE: This cross-sectional study investigated the relationships between
psychiatric and substance-related disorders, high-risk behaviors, and the onset,
duration, and frequency of homelessness among homeless youth in Chicago. METHODS:
Sixty-six homeless youth were recruited from two shelters in Chicago. Demographic
characteristics, psycho-pathology, substance use, and risk behaviors were
assessed for each participant. RESULTS: Increased frequency and duration of
homeless episodes were positively correlated with higher rates of psychiatric
diagnoses. Increased number of psychiatric diagnoses was positively correlated
with increased high-risk behaviors. Participants with diagnoses of Current
Suicidality, Manic Episodes, Obsessive Compulsive Disorder, Substance Abuse, and
Psychotic Disorder had a higher chronicity of homelessness than those without
diagnoses. CONCLUSIONS: Significant differences were evident between the three
time parameters, suggesting that stratification of data by different time
variables may benefit homelessness research by identifying meaningful subgroups
who may benefit from individualized interventions.
PMID- 25130235
TI - Substance use, risk of dependence, counseling and treatment among adult health
center patients.
AB - Health centers provide primary care to 20 million underserved patients. We
examined the prevalence of substance use and risk of dependence among health
center patients, and identified factors associated with desire for
counseling/treatment and discussions about substance use with a doctor. National
data on 3,949 adults came from the 2009 Health Center Patient Survey. Forty
percent of patients reported past-year binge drinking, 14% of patients had used
any drug in the past three months, and 13% of these recent users were at high
risk of dependence. Eighty-four percent of patients who desired substance use
counseling or treatment reported receiving it. Several factors were associated
with patients discussing substance use with their doctors (e.g., younger age,
being male, severe mental illness, current smoking). Patients most likely to
desire substance use counseling or treatment were male, unmarried, insured,
current smokers, and indicated mental health problems.
PMID- 25130236
TI - Homelessness and risk of end-stage renal disease.
AB - To identify homeless people with chronic kidney disease (CKD) who were at highest
risk for end-stage renal disease (ESRD), we studied 982 homeless and 15,674
domiciled people with CKD receiving public health care. We developed four risk
prediction models for the primary outcome of ESRD. Overall, 71 homeless and 888
domiciled people progressed to ESRD during follow-up (median: 6.6 years).
Homeless people with CKD experienced significantly higher incidence rates of ESRD
than poor but domiciled peers. Most homeless people who developed progressive CKD
were readily identifiable well before ESRD using a prediction model with five
common variables. We estimated that program following homeless people in the
highest decile of ESRD risk would have captured 64-85% of those who eventually
progressed to ESRD within five years. Thus, an approach targeting homeless people
at high risk for ESRD appears feasible and could reduce substantial morbidity and
costs incurred by this highly vulnerable group.
PMID- 25130237
TI - The impact of obesity on medication use and expenditures among nonelderly adults
with asthma.
AB - Obesity contributes substantially to health resource use and costs. This study
examines the impact of obesity on medication use and expenditures among
nonelderly adults with asthma using the Medical Expenditure Panel Survey. Obese
classes II/III individuals were more likely to have current asthma, seek
treatment for asthma, use more medications, and have higher medication and health
care expenditures compared with normal weight individuals. Multivariate results
indicate that if obese classes II/III were normal weight the probability of
asthma treatment would decrease by 8.0 percentage points. Conditional on any
asthma treatment, if obese classes II/III were normal weight the mean number of
total prescribed medications would decrease by 19.42 fills, and expected
expenditures on total prescribed medications and health care would decrease by
$1,738.68 and $3,682.58, respectively. These results suggest that, all else
equal, reduction in body weight may help reduce health resource use and
expenditures for nonelderly adults with asthma.
PMID- 25130238
TI - Affecting African American men's prostate cancer screening decision-making
through a mobile tablet-mediated intervention.
AB - African American men experience a 60% higher incidence of prostate cancer and are
more than twice as likely to die from it than White men. Evidence is insufficient
to conclude that definitively screening for prostate cancer reduces the
likelihood of morbidity or death. Patients are encouraged to discuss screening
alternatives with health care providers for informed decision-making (IDM). The
extent of IDM in clinical or community setting is not known. This study uses data
from a community-based, computer-mediated, IDM intervention that targeted 152
African American aged 40 to 70. Pretest-posttest differences in means for
prostate cancer knowledge, screening decisional conflict, and screening
decisional self-efficacy were examined by two-tailed t-tests. Overall, the
intervention significantly improved respondents' prostate cancer knowledge
(p<.0001), significantly improved decisional self-efficacy (p<.0001) and
significantly reduced decisional conflict (p<.0001). Specifically, the
intervention significantly promoted IDM among men who reported more education,
being married, having financial resources, and younger age.
PMID- 25130240
TI - Structural vulnerability and problem drinking among Latino migrant day laborers
in the San Francisco Bay Area.
AB - Latino migrant day laborers (LMDLs) live under challenging conditions in the San
Francisco Bay Area. This study explored day laborer alcohol use guided by a
structural vulnerability framework, specifically problem vs. non-problem drinking
as perceived by LMDLs and how they cope with or try to avoid problem drinking
given their broader environment. The study utilized ethnographic methods
including in-depth semi-structured qualitative interviews with 51 LMDLs. Findings
revealed the considerable challenge of avoiding problem drinking given socio
environmental factors that influence drinking: impoverished living and working
conditions, prolonged separation from home and family, lack of work
authorization, consequent distress and negative mood states, and peer pressure to
drink. While participants shared strategies to avoid problem drinking, the
success of individual-level efforts is limited given the harsh structural
environmental factors that define day laborers' daily lives. Discussed are
implications for prevention and intervention strategies at the individual,
community, national and international levels.
PMID- 25130239
TI - Trust in health care providers: factors predicting trust among homeless veterans
over time.
AB - We examined whether a combination of predisposing, enabling, need, and primary
care experience variables would predict trust in medical health care providers
for homeless veterans over 18 months. Linear mixed model analysis indicated that,
among these variables, race, social support, service-connected disability status,
and satisfaction and continuity with providers predicted trust in provider over
time. Trust in providers improved during the initial stages of the relationship
between patient and provider and then declined to slightly below baseline levels
over time. Further research is needed to determine generalizability and effects
of provider trust on patient health care status over longer periods of time.
PMID- 25130242
TI - Injectable Contraceptive Continuation among Female Exotic Dancers Seeking Mobile
Reproductive Health Services.
AB - OBJECTIVES: We describe depot medroxyprogesterone acetate (DMPA) continuation
patterns among female exotic dancers receiving reproductive health services at a
mobile syringe exchange. METHODS: Clients initiating DMPA between November 2009
and August 2012 were identified retrospectively via chart review. Life table
analysis measured continuation. Client characteristics were compared using chi
square tests. RESULTS: Sixty nine clients were identified; 72% were African
American and 63% were younger than 25. At three months, 36% of the study sample
continued DMPA; those continuing were more likely to be White (p=0.01) and
receive other services (p=.01). The 12-month cumulative continuation probability
was 0.09. Considering those who had received an injection, continuation
proportions were higher (46% at 6; 71% at 12 months). CONCLUSIONS: A subset of
female exotic dancers may favor DMPA as a long term contraceptive. Integrating
mobile reproductive health services into public health programs can help fulfill
the unique health needs of this high-risk population.
PMID- 25130241
TI - Contraceptive implant knowledge and practices of providers serving an urban, low
income community.
AB - Contraceptive implants are highly effective but infrequently used by low-income
women, who are at high risk of unintended pregnancy. Provider factors that may
affect implant acceptance merit further exploration. We surveyed 66 clinicians
serving an urban, low-income community from adult primary care, women's health,
and adolescent practices. We assessed implant education, knowledge, perceptions
of accessibility and cost, and patient selection practices. Education about
implants varied from 15% in adult primary care to 30% in adolescent practice and
75% in women's health. Among women's health providers, 54% were trained to insert
implants. Despite having eligible candidates, some providers were unlikely to
recommend implants to patients who are nulliparous (8%), teens (22%), depressed
(24%) or obese (22%). Forty-one percent of providers reported insertion wait
times of at least three weeks. Among low-income women, deficits in provider
education, restrictive practice patterns, and long insertion wait times may
affect contraceptive implant use.
PMID- 25130243
TI - African American male and female student perceptions of Pulvers Body Images:
implications for obesity, health care, and prevention.
AB - Differences in male and female perception response to the Pulvers Body Image
Scale (PBIS) were examined among 356 freshmen African American students attending
an urban historically Black college/university (HBCU). Participants completed a
questionnaire identifying images that best represented their current, healthy,
and ideal body image. Compared with males, more females selected the normal body
image as their ideal (63.3% vs. 15.3%) and healthy body shape (59.3% vs. 15.3%)
(p<.001). Compared with females, more males selected the overweight body image as
their ideal (44.6% vs. 30.2%) and healthy body shape (52.2% vs. 36.2%) (p<.01).
Similarly, more males selected the obese body image as their ideal (40.1% vs.
6.5%) and healthy body shape (32.5% vs. 4.5%) compared with females (p<.001).
Male freshmen at an HBCU perceive a larger body image as healthy and ideal more
often than their female counterparts, thereby increasing the potential for their
weight-related health risks.
PMID- 25130244
TI - Are female college students who are diagnosed with depression at greater risk of
experiencing sexual violence on college campus?
AB - We examined the association between depression and sexual violence among 18-24
year-old female college students using National College Health Assessment survey.
Data were collected from a nationally representative sample of 10,541 female
students on 33 college campuses. Results showed that female students who were
reportedly ever diagnosed with depression were 1.56 times more likely than those
who had never been diagnosed with depression to have experienced sexual violence.
Female students who had one or more sexual partners currently were found 3.17
times more likely than those who had no sexual partner to have experienced sexual
violence; similarly, female students who engaged in binge drinking in the
previous two weeks were found about two times more likely than their counterparts
to have experienced sexual violence. Depression is a public health issue and must
be addressed sooner rather than later in order to reduce and prevent sexual
violence on college campuses.
PMID- 25130246
TI - Medicare eligibility age, health disparities, and medicare reform.
AB - Medicare eligibility age is a major focus of health policy discussions about how
to tackle increasing health care costs and reduce the national debt. Raising the
Medicare eligibility age from 65 to 67 would presumably reduce the cost of
Medicare, but the opponents caution it could exacerbate health disparities by
race and/or income. We compared the mortality rate, hospitalization rate, and
annual Medicare expenditures of current White and Black Medicare beneficiaries at
age 65-66 years using the Medicare Current Beneficiary Survey. We found Blacks
have higher health care demand reimbursed by Medicare than Whites at these ages.
To raise the Medicare eligibility age from 65 to 67 would likely have more
negative health and economic effects among Blacks than among Whites, and would
likely exacerbate health disparities by race. We suggest great caution when
considering this policy option.
PMID- 25130247
TI - Hospital practices in the collection of patient race, ethnicity, and language
data: a statewide survey, California, 2011.
AB - California mandates hospitals to collect and report patient race, ethnicity, and
primary spoken language (REL). A lack of specific guidelines and standardized
practices on how data should be collected has contributed to inconsistent and
incomplete data.General acute care hospitals in California completed a survey to
elucidate practices regarding collection and auditing of patient REL. Nearly all
hospitals reported collecting race and/or ethnicity (97%). The majority of
hospitals used standardized forms for collection, and 75% audited patient
information for completeness. Popular accepted strategies to improve the quality
and completeness of REL included collecting data at the first encounter, routine
staff training, incorporating REL questions into existing admissions forms, and
developing and enforcing hospital policies regarding data collection.California
hospitals are collecting information on patient REL as mandated, but variation in
data collection exists. Hospitals endorse many reasonable approaches for
standardization, and may benefit from standardized data collection and auditing
practices.
PMID- 25130245
TI - HIV testing and engagement in care among highly vulnerable female sex workers:
implications for treatment as prevention models.
AB - BACKGROUND: Although emerging Treatment as Prevention models can be effective in
reducing HIV incidence among high-risk populations, many HIV infected individuals
remain undiagnosed or fail to engage in HIV care. METHODS: This study examined
the factors associated with HIV testing and care among a population of substance
using female sex workers. RESULTS: Recent HIV testing was associated with higher
education level, having a regular health care provider or clinic, recent crack
use, and higher sexual risk behaviors; HIV treatment utilization was associated
with higher levels of social support, having a regular health care provider or
clinic, housing stability and insurance coverage. Qualitative data revealed HIV
related stigma, denial, social isolation, and substance use as barriers to HIV
testing and treatment; social support and accessibility of services were key
enablers. CONCLUSIONS: Improving HIV testing and linkage to treatment among
female sex workers will require structural initiatives to reduce stigma and
increase service seeking support.
PMID- 25130249
TI - Race/ethnicity and other social determinants of psychological well-being and
functioning in mental health clinics.
AB - Significant racial and ethnic differences exist in the receipt of psychiatric
care and help-seeking. We examined the relationship between race/ethnicity and
psychological well-being and functioning in psychiatric outpatients. We analyzed
intake data for 8,697 adult patients in psychiatry clinics in New England between
2008 and 2010. Patients rated psychological wellbeing using the Schwartz Outcome
Scale (SOS-10); clinicians rated the Global Assessment of Functioning (GAF). In
an analysis of variance with covariates, race/ethnicity exhibited a small but
statistically significant association with GAF (F(4,8481)=17.902, p<.001) and SOS
10 scores (F(4,8165)=7.271, p<.001). However, after adjustment for physical
health and socioeconomic variables, these differences became insignificant or
were reversed. Our findings suggest that the relationship between race/ethnicity
and mental health may be confounded by other socioeconomic or health differences
and may be small compared with the effect of those variables. Future studies on
race and psychological well-being should take social determinants of health into
consideration.
PMID- 25130248
TI - The development of the DSM-5 Cultural Formulation Interview-Fidelity Instrument
(CFI-FI): a pilot study.
AB - This paper reports on the development of the Cultural Formulation Interview
Fidelity Instrument (CFI-FI) which assesses clinician fidelity to the DSM-5
Cultural Formulation Interview (CFI). The CFI consists of a manualized set of
standard questions that can precede every psychiatric evaluation. It is based on
the DSM-IV Outline for Cultural Formulation, the cross-cultural assessment with
the most evidence in psychiatric training. Using the New York sample of the DSM-5
CFI field trial, two independent raters created and finalized items for the CFI
FI based on six audio-taped and transcribed interviews. The raters then used the
final CFI-FI to rate the remaining 23 interviews. Inter-rater reliability ranged
from .73 to 1 for adherence items and .52 to 1 for competence items. The
development of the CFI-FI can help researchers and administrators determine
whether the CFI has been implemented with fidelity, permitting future
intervention research.
PMID- 25130251
TI - Opting to opt-in: policy choice, program expectations and results in West
Virginia's Medicaid reform initiative.
AB - Following the passage of the Federal Deficit Reduction Act in 2005, a few states,
including West Virginia, redesigned their Medicaid programs to emphasize personal
responsibility and consumer-driven health decisions. The West Virginia program
was implemented in 2006 and was subsequently abandoned in 2010 due to changes in
Federal laws and continuing criticism by advocacy groups whose expectations for
enrollment in a wellness-based plan were not met. Using the results of a survey
of the West Virginia members, the authors explore the public policy and
implementation factors of this program. We argue that initial policy design
relied on existing implementation mechanisms, while it needed specific tactics to
address the novelty of the choice members were facing. With the passage of the
Patient Protection and Affordable Care Act, the West Virginia results provide
valuable insights for future health reform policy implementation, especially as
they relate to consumer-directed health decision-making and the role of
intermediaries who can play a role in assisting consumers in their choices.
PMID- 25130250
TI - The pattern of association between U.S. economic indicators and infant mortality
rates at the state level.
AB - This cross-sectional ecological study examines the pattern of association of
state income and income inequality (measured by Gini coefficient) with state
infant mortality rates (IMRs) in the U.S. Scatter plots and correlation
coefficients were used to examine bivariate associations and bubble plots to
examine three-way relationships. Infant mortality rate was positively associated
with Gini (R=0.397, p=.004) and negatively with income (R=-0.482, p <.001).
However using Black and White IMRs, the associations with Gini were non
significant, but with income remained significant. The bubble plot of Gini versus
White IMR (income represented by bubble size) showed increasing IMR as Gini
increases and income decreases, except for a subgroup of high-gini, high-income
states with low IMRs. State income appears to be a stronger and more consistent
predictor of U.S. IMRs for both Black and White races and can explain the pattern
of association of White IMR with state Gini coefficient.
PMID- 25130254
TI - Ag2S-hollow Fe2O3 nanocomposites with NIR photoluminescence.
AB - A facile synthesis of Ag2S-hollow Fe2O3 nanocomposites with NIR photoluminescence
was firstly demonstrated by the sulfidation of Ag-Fe2O3 core-shell nanoparticles.
Characteristic morphology transformations along with color changes were recorded
and a mechanism was proposed for the sulfidation process, which can provide new
possibilities to fabricate other complex nanostructures.
PMID- 25130255
TI - Case of radioactive iodine exposure during pregnancy.
AB - A 43-year-old woman (gravida 0, para 0) was diagnosed with thyroid carcinoma and
had been receiving radioactive iodine for remnant ablation. Eventually, her
pregnant status became apparent; during radiation, she was at 5 gestational
weeks. She decided to continue the pregnancy and delivered a boy of 2362 g at 37
gestational weeks. The infant did not present thyroid dysfunction or
developmental abnormalities at 2 months of age. The patient was in the early
pregnancy stage during radiation, so the fetus did not develop radiation-related
damage of the thyroid gland because at this stage, the fetal thyroid does not
concentrate iodine. Although the mother had received radioactive iodine during
the critical organogenesis period, the fetus did not develop teratogenicity
because the radiation was administered at the borderline threshold for
teratogenicity. This case suggests the importance of iodine thyroid absorption
when considering radiation-related damage to the fetal thyroid gland during early
pregnancy.
PMID- 25130257
TI - WITHDRAWN: Laparoscopic surgery for pelvic pain associated with endometriosis.
PMID- 25130256
TI - Vertical inhibition of the MAPK pathway enhances therapeutic responses in NRAS
mutant melanoma.
AB - The MEK inhibitor MEK162 is the first targeted therapy agent with clinical
activity in patients whose melanomas harbor NRAS mutations; however, median PFS
is 3.7 months, suggesting the rapid onset of resistance in the majority of
patients. Here, we show that treatment of NRAS-mutant melanoma cell lines with
the MEK inhibitors AZD6244 or trametinib resulted in a rebound activation of
phospho-ERK (pERK). Functionally, the recovery of signaling was associated with
the maintenance of cyclin-D1 expression and therapeutic escape. The combination
of a MEK inhibitor with an ERK inhibitor suppressed the recovery of cyclin-D1
expression and was associated with a significant enhancement of apoptosis and the
abrogation of clonal outgrowth. The MEK/ERK combination strategy induced greater
levels of apoptosis compared with dual MEK/CDK4 or MEK/PI3K inhibition across a
panel of cell lines. These data provide the rationale for further investigation
of vertically co-targeting the MAPK pathway as a potential treatment option for
NRAS-mutant melanoma patients.
PMID- 25130258
TI - WITHDRAWN: Laparoscopic surgery for subfertility associated with endometriosis.
PMID- 25130260
TI - Mechanistic aspects of thioflavin-T self-aggregation and DNA binding: evidence
for dimer attack on DNA grooves.
AB - Thioflavin-T (TFT) is a fluorescent marker widely employed in biomedical research
but the mechanism of its binding to polynucleotides has been poorly understood.
This paper presents a study of the mechanisms of TFT self-aggregation and binding
to DNA. Relaxation kinetics of TFT solutions show that the cyanine undergoes
dimerization followed by dimer isomerisation. The interaction of TFT with DNA has
been investigated using static methods, such as spectrophotometric and
spectrofluorometric titrations under different conditions (salt content,
temperature), fluorescence quenching, viscometric experiments and the T-jump
relaxation method. The combined use of these techniques enabled us to show that
the TFT monomer undergoes intercalation between the DNA base pairs and external
binding according to a branched mechanism. Moreover, it has also been observed
that, under dye excess conditions, the TFT dimer binds to the DNA grooves. The
molecular structures of intercalated TFT and the groove-bound TFT dimer are
obtained by performing QM/MM MD simulations.
PMID- 25130261
TI - Reactivity of cosmetic UV filters towards skin proteins: model studies with Boc
lysine, Boc-Gly-Phe-Gly-Lys-OH, BSA and gelatin.
AB - OBJECTIVE: Organic UV filters are used as active ingredients in most sunscreens
and also in a variety of daily care products. Their good (photo) stability is of
special interest to guarantee protective function and to prevent interactions
with the human skin. Due to the mostly electrophilic character of the UV filters,
reactions with nucleophilic protein moieties like lysine side chains are
conceivable. Prior studies showed that the UV filters octocrylene (OCR), butyl
methoxydibenzoylmethane (BM-DBM), ethylhexyl salicylate (EHS), ethylhexyl
methoxycinnamate (EHMC), benzophenone-3 (BP-3), ethylhexyl triazone (EHT) and
dibenzoylmethane (DBM) were able to covalently bind to an HPTLC amino phase and
the amino acid models ethanolamine and butylamine after slightly heating and/or
radiation. METHODS: Boc-protected lysine, the tetrapeptide Boc-Gly-Phe-Gly-Lys
OH, bovine serum albumin (BSA) and porcine gelatin were used as more complex
models to determine the reactivity of the mentioned UV filters towards skin
proteins under thermal or UV irradiation conditions. RESULTS: After gentle
heating at 37 degrees C, benzophenone imines were identified as reaction products
of BP-3 and OCR with Boc-lysine and the tetrapeptide, whereas DBM and BM-DBM
yielded enamines. For EHMC, a Michael-type reaction occurred, which resulted in
addition of Boc-lysine or the tetrapeptide to the conjugated double bond. Ester
aminolysis of EHS and EHT mainly afforded the corresponding amides. Reactions of
the UV filters with BSA changed the UV spectrum of BSA, generally associated with
an increase of the absorption strength in the UVA or UVB range. For all protein
models, the UV filters showed an increasing reactivity in the order EHT < EHMC <
EHS < BP-3 < OCR < DBM < BM-DBM. CONCLUSION: Especially the UV absorbers BM-DBM,
OCR and BP-3, which are seen as common allergens or photoallergens, showed a high
reactivity towards the different skin protein models. As the formation of protein
adducts is recognized as important key element in the induction of skin
sensitization, the results of this study can contribute to a better understanding
of the underlying chemical mechanisms of such reactions.
PMID- 25130259
TI - Myc inhibition is effective against glioma and reveals a role for Myc in
proficient mitosis.
AB - Gliomas are the most common primary tumours affecting the adult central nervous
system and respond poorly to standard therapy. Myc is causally implicated in most
human tumours and the majority of glioblastomas have elevated Myc levels. Using
the Myc dominant negative Omomyc, we previously showed that Myc inhibition is a
promising strategy for cancer therapy. Here, we preclinically validate Myc
inhibition as a therapeutic strategy in mouse and human glioma, using a mouse
model of spontaneous multifocal invasive astrocytoma and its derived
neuroprogenitors, human glioblastoma cell lines, and patient-derived tumours both
in vitro and in orthotopic xenografts. Across all these experimental models we
find that Myc inhibition reduces proliferation, increases apoptosis and
remarkably, elicits the formation of multinucleated cells that then arrest or die
by mitotic catastrophe, revealing a new role for Myc in the proficient division
of glioma cells.
PMID- 25130263
TI - Drought effect on plant nitrogen and phosphorus: a meta-analysis.
AB - Climate change scenarios forecast increased aridity in large areas worldwide with
potentially important effects on nutrient availability and plant growth. Plant
nitrogen and phosphorus concentrations (plant [N] and [P]) have been used to
assess nutrient limitation, but a comprehensive understanding of drought stress
on plant [N] and [P] remains elusive. We conducted a meta-analysis to examine
responses of plant [N] and [P] to drought manipulation treatments and duration of
drought stress. Drought stress showed negative effects on plant [N] (-3.73%) and
plant [P] (-9.18%), and a positive effect on plant N:P (+ 6.98%). Drought stress
had stronger negative effects on plant [N] and [P] in the short term (< 90 d)
than in the long term (> 90 d). Drought treatments that included drying-rewetting
cycles showed no effect on plant [N] and [P], while constant, prolonged, or
intermittent drought stress had a negative effect on plant [P]. Our results
suggest that negative effects on plant [N] and [P] are alleviated with extended
duration of drought treatments and with drying-rewetting cycles. Availability of
water, rather than of N and P, may be the main driver for reduced plant growth
with increased long-term drought stress.
PMID- 25130262
TI - Youth depression alleviation: the Fish Oil Youth Depression Study (YoDA-F): A
randomized, double-blind, placebo-controlled treatment trial.
AB - AIM: US authorities have recommended 'black-box' warnings for antidepressants
because of the increased risk of suicidality for individuals up to age 25. There
is thus a clinical and ethical imperative to provide effective treatment for
youth depression with an acceptable risk-benefit balance. Long-chain omega-3
polyunsaturated fatty acids (PUFAs) play an important role in a range of
physiological processes in living organisms. Supplementation with omega-3 PUFAs
has been shown to have a range of beneficial effects on both physical and mental
health, and results of previous trials suggest that omega-3 PUFAs may be a safe
and effective treatment for depression. However, conclusions from these trials
have been limited by their relatively small sample sizes. METHODS: This trial
will test the effectiveness of a 12-week parallel group, double-blind,
randomized, placebo-controlled trial of 1.4 g day(-1) omega-3 PUFAs in help
seeking 15- to 25-year-olds (N = 400) presenting with major depressive disorder.
The primary hypothesis is that young people will show greater improvement of
depressive symptoms after 12 weeks of treatment with omega-3 PUFAs plus cognitive
behavioural case management compared with treatment with placebo plus cognitive
behavioural case management. CONCLUSION: Because of using a large sample, results
from this study will provide the strongest evidence to date to inform the use of
omega-3 PUFAs as first-line therapy in young people presenting with major
depressive disorder. The study also heralds an important step towards indicated
prevention of persistent depression, which may reduce the burden, stigmatization,
disability and economic consequences of this disorder.
PMID- 25130264
TI - Use of porcine luteinizing hormone at oestrous onset in a protocol for fixed-time
artificial insemination in gilts.
AB - The aim of this study was to evaluate the effect of porcine luteinizing hormone
(pLH) given at oestrous onset in gilts, by different routes and doses, on the
interval between onset of oestrus and ovulation (IOEO) and reproductive
performance using a single fixed-time artificial insemination (FTAI). A total of
153 gilts were submitted to oestrous detection at 8-h intervals and assigned to
three groups: control - without hormone application and inseminated at 0, 24 and
48 h after oestrous onset; VS2.5FTAI - 2.5 mg pLH by the vulvar submucosal route
at oestrous onset and a single FTAI 16 h later; IM5FTAI - 5 mg pLH by the
intramuscular route at oestrous onset and a single FTAI 16 h later. More
VS2.5FTAI gilts (47.1%; p < 0.05) ovulated within 24 h after oestrous onset than
control gilts (25.5%) whereas IM5FTAI gilts had an intermediate percentage
(31.4%; p > 0.05). The IOEO tended to be shorter (p = 0.06) in VS2.5FTAI (30.2 +/
1.4 h) than in control (34.7 +/- 1.4 h) gilts, but there was no difference (p >
0.05) between control and IM5FTAI (32.8 +/- 1.4 h) gilts. Farrowing rate was not
different (p > 0.05) among treatments. Total born piglets (TB) was lower (p <
0.05) in VS2.5FTAI (12.3 +/- 0.4) than in control gilts (14.1 +/- 0.4), whereas
intermediate TB was observed in IM5FTAI gilts (13.3 +/- 0.4). Due to the
advancement of ovulation, reduction of the hormonal dose and the ease of
application, the vulvar submucosal route would be the best option for FTAI
protocols, but their negative impact on litter size remains to be elucidated.
Taking into account the good fertility results obtained in IM5FTAI gilts whose
ovulation was not advanced, the possibility of a single FTAI without any hormonal
treatment should be further investigated, to establish reliable FTAI protocols
for gilts.
PMID- 25130266
TI - Sublingual immunotherapy alters expression of IL-4 and its soluble and membrane
bound receptors.
AB - Seasonal allergic rhinitis (SAR) is a disease of increasing prevalence, which
results from an inappropriate T helper cell, type 2 (Th2) response to pollen.
Specific immunotherapy (SIT) involves repeated treatment with small doses of
pollen and can result in complete and lasting reversal of SAR. Here, we assayed
the key Th2 cytokine, IL-4, and its soluble and membrane-bound receptor in
patients with SAR before and after SIT. Using allergen-challenge assays, we found
that SIT treatment decreased IL-4 cytokine levels, as previously reported. We
also observed a significant decrease in the IL-4 membrane-bound receptor (mIL4R)
at the level of both mRNA and protein. SIT treatment resulted in a significant
increase in the inhibitory soluble IL-4 receptor (sIL4R). Reciprocal changes in
mIL4R and sIL4R were also observed in patient serum. Altered mIL4R and sIL4R is a
novel explanation for the positive effects of immunotherapy with potential basic
and clinical research implications.
PMID- 25130265
TI - The association between depressive symptoms from early to late adolescence and
later use and harmful use of alcohol.
AB - Depressive symptoms and alcohol misuse contribute substantially to the global
health burden. These phenotypes often manifest, and frequently co-occur, during
adolescence. However, few studies have examined whether both baseline levels of
depressive symptoms and change in symptoms are associated with alcohol outcomes.
In addition, inconsistent findings could be due to sex differences or the use of
different alcohol outcomes. Using data from a prospective population-based cohort
in the UK, we estimated trajectories of depressive symptoms from 12 years 10
months to 17 years 10 months, separately for male and female participants. We
assessed whether baseline and change in depressive symptoms were associated with
use and harmful use of alcohol at 18 years 8 months. Among females, increasing
depressive symptoms were associated with increased alcohol use; whilst for males,
there was little evidence of this. When examining harmful levels of alcohol use,
baseline levels of depressive symptoms in males were weakly related to later
harmful alcohol use but this association was attenuated substantially through
adjustment for confounders. In contrast, both baseline symptoms and increase in
symptoms were associated with later harmful alcohol use in females and these
associations were not diminished by confounder adjustment. Elevated depressive
symptoms during adolescence are positively associated with increases in both use
and harmful use of alcohol at 18 years 8 months. These findings differ between
the sexes. Further research is needed to examine the mechanisms underlying the
link between depressive symptoms and harmful alcohol use to identify potentially
modifiable factors for intervention.
PMID- 25130268
TI - Bone loss and fractures in limbs paralyzed by spinal cord injury: Prevention,
diagnosis, and treatment.
PMID- 25130269
TI - Reflections on the enduring value of critical scholarship.
PMID- 25130267
TI - Quantitative relations between the eyeball, the optic nerve, and the optic canal
important for intracranial pressure monitoring.
AB - OBJECTIVE: To find correlations between diameters of the optic nerve sheath
(ONSD), the eyeball, and the optic canal that might be important for intracranial
pressure monitoring. METHODS: In a prospective cohort study, the CT data of
consecutive 400 adults (18+) with healthy eyes and optic nerves and absence of
neurological diseases were collected and analyzed. When the CT scans were
obtained, the diameters of the optic nerve sheath, the eyeball, and the optic
canal were measured and statistically analyzed. The data obtained from the left
and from the right eyeballs and optic nerves were compared. The correlation
analysis was performed within these variables, with the gender, and the age.
RESULTS: In healthy persons, the ONSD varies from 3.65 mm to 5.17 mm in different
locations within the intraorbital space with no significant difference between
sexes and age groups. There is a strong correlation between the eyeball
transverse diameter (ETD) and ONSD that can be presented as ONSD/ETD index. In
healthy subjects, the ONSD/ETD index equals 0.19. CONCLUSION: The calculation of
an index when ONSD is divided by the ETD of the eyeball presents precise
normative database for ONSD intracranial pressure measurement technique. When the
ONSD is measured for intracranial pressure monitoring, the most stable results
can be obtained if the diameter is measured 10 mm from the globe. These data
might serve as a normative database at emergency departments and in general
neurological practice.
PMID- 25130270
TI - Image analysis of skin color heterogeneity focusing on skin chromophores and the
age-related changes in facial skin.
AB - BACKGROUND/PURPOSE: Heterogeneity with respect to skin color tone is one of the
key factors in visual perception of facial attractiveness and age. However, there
have been few studies on quantitative analyses of the color heterogeneity of
facial skin. The purpose of this study was to develop image evaluation methods
for skin color heterogeneity focusing on skin chromophores and then characterize
ethnic differences and age-related changes. METHODS: A facial imaging system
equipped with an illumination unit and a high-resolution digital camera was used
to develop image evaluation methods for skin color heterogeneity. First, melanin
and/or hemoglobin images were obtained using pigment-specific image-processing
techniques, which involved conversion from Commission Internationale de
l'Eclairage XYZ color values to melanin and/or hemoglobin indexes as measures of
their contents. Second, a spatial frequency analysis with threshold settings was
applied to the individual images. Cheek skin images of 194 healthy Asian and
Caucasian female subjects were acquired using the imaging system. Applying this
methodology, the skin color heterogeneity of Asian and Caucasian faces was
characterized. RESULTS: The proposed pigment-specific image-processing techniques
allowed visual discrimination of skin redness from skin pigmentation. In the
heterogeneity analyses of cheek skin color, age-related changes in melanin were
clearly detected in Asian and Caucasian skin. Furthermore, it was found that the
heterogeneity indexes of hemoglobin were significantly higher in Caucasian skin
than in Asian skin. CONCLUSION: We have developed evaluation methods for skin
color heterogeneity by image analyses based on the major chromophores, melanin
and hemoglobin, with special reference to their size. This methodology focusing
on skin color heterogeneity should be useful for better understanding of aging
and ethnic differences.
PMID- 25130271
TI - Hsp27 regulates EGF/beta-catenin mediated epithelial to mesenchymal transition in
prostate cancer.
AB - Increased expression of the molecular chaperone Hsp27 is associated with the
progression of prostate cancer (PCa) to castration-resistant disease, which is
lethal due to metastatic spread of the prostate tumor. Metastasis requires
epithelial to mesenchymal transition (EMT), which endows cancer cells with the
ability to disseminate from the primary tumor and colonize new tissue sites. A
wide variety of secreted factors promote EMT, and while overexpression and
constitutive activation of epidermal growth factor (EGF) signaling is associated
with poor prognosis of PCa, a precise role of EGF in PCa progression to
metastasis remains unclear. Here, we show that Hsp27 is required for EGF-induced
cell migration, invasion and MMPs activity as well as the expression of EMT
markers including Fibronectin, Vimentin and Slug with concomitant decrease of E
cadherin. Mechanistically, we found that Hsp27 is required for EGF-induced AKT
and GSK3beta phosphorylation and beta-catenin nuclear translocation. Moreover,
silencing Hsp27 decreases EGF dependent phosphorylation of beta-catenin on
tyrosine 142 and 654, enhances beta-catenin ubiquitination and degradation,
prevents beta-catenin nuclear translocation and binding to the Slug promoter.
These data suggest that Hsp27 is required for EGF-mediated EMT via modulation of
the beta-catenin/Slug signaling pathway. Together, our findings underscore the
importance of Hsp27 in EGF induced EMT in PCa and highlight the use of Hsp27
knockdown as a useful strategy for patients with advanced disease.
PMID- 25130272
TI - Cochlear implantation in children with bacterial meningitic deafness: The
influence of the degree of ossification and obliteration on impedance and charge
of the implant.
AB - OBJECTIVES: To determine impedance values and charge consumption following
cochlear implantation post-meningitic deaf children depending on the grade of
cochlear ossification and obliteration. METHODS: Post-meningitic deaf (n=49) and
control (n=43) children treated with cochlear implants were included in the
study. Impedance and charge values were calculated for each group. The degree of
ossification of the cochlea was evaluated from a high-resolution computed
tomography (HRCT) scan whereas the degree of obliteration was determined
intraoperatively by the surgeon. RESULTS: Pneumococci were the principal pathogen
responsible for bacterial meningitis, followed by meningococci. In HRCT scans,
the degree of ossification was 1 and 2 in 29% of patients. The results of the
intraoperative assessment of the cochlea showed obliteration grade 1 in 38% and
grade 2 in 23% of cases. Children in the meningitis group showed significant
higher impedances comparing to the control group. A significantly increased
charge consumption was observed in patients with a grade 2 ossification when
compared to those without ossification (P=0.02). Discussion Cochlea implanted
children with meningitis-related deafness exhibit higher impedances, especially
in the region of the basal and middle turn, however, not depending on the degree
of cochlear ossification. High impedances and charge in the meningitis group may
be explained by alterations in the central auditory pathway or on the electrode
surface. CONCLUSION: To optimize the outcome in post-meningitic deaf children,
surgery is advisable at an early stage prior to the onset of cochlear
ossification.
PMID- 25130273
TI - The yeast oligopeptide transporter Opt2 is localized to peroxisomes and affects
glutathione redox homeostasis.
AB - Glutathione, the most abundant small-molecule thiol in eukaryotic cells, is
synthesized de novo solely in the cytosol and must subsequently be transported to
other cellular compartments. The mechanisms of glutathione transport into and out
of organelles remain largely unclear. We show that budding yeast Opt2, a close
homolog of the plasma membrane glutathione transporter Opt1, localizes to
peroxisomes. We demonstrate that deletion of OPT2 leads to major defects in
maintaining peroxisomal, mitochondrial, and cytosolic glutathione redox
homeostasis. Furthermore, ?opt2 strains display synthetic lethality with
deletions of genes central to iron homeostasis that require mitochondrial
glutathione redox homeostasis. Our results shed new light on the importance of
peroxisomes in cellular glutathione homeostasis.
PMID- 25130275
TI - Continuous eclogite melting and variable refertilisation in upwelling
heterogeneous mantle.
AB - Large-scale tectonic processes introduce a range of crustal lithologies into the
Earth's mantle. These lithologies have been implicated as sources of
compositional heterogeneity in mantle-derived magmas. The model being explored
here assumes the presence of widely dispersed fragments of residual eclogite
(derived from recycled oceanic crust), stretched and stirred by convection in the
mantle. Here we show with an experimental study that these residual eclogites
continuously melt during upwelling of such heterogeneous mantle and we
characterize the melting reactions and compositional changes in the residue
minerals. The chemical exchange between these partial melts and more refractory
peridotite leads to a variably metasomatised mantle. Re-melting of these
metasomatised peridotite lithologies at given pressures and temperatures results
in diverse melt compositions, which may contribute to the observed heterogeneity
of oceanic basalt suites. We also show that heterogeneous upwelling mantle is
subject to diverse local freezing, hybridization and carbonate-carbon-silicate
redox reactions along a mantle adiabat.
PMID- 25130274
TI - Microglial regulation of immunological and neuroprotective functions of
astroglia.
AB - Microglia and astroglia play critical roles in the development, function, and
survival of neurons in the CNS. However, under inflammatory conditions the role
of astrogliosis in the inflammatory process and its effects on neurons remains
unclear. Here, we used several types of cell cultures treated with the bacterial
inflammogen LPS to address these questions. We found that the presence of
astroglia reduced inflammation-driven neurotoxicity, suggesting that astrogliosis
is principally neuroprotective. Neutralization of supernatant glial cell line
derived neurotrophic factor (GDNF) released from astroglia significantly reduced
this neuroprotective effect during inflammation. To determine the immunological
role of astroglia, we optimized a highly-enriched astroglial culture protocol and
demonstrated that LPS failed to induce the synthesis and release of TNF-alpha and
iNOS/NO. Instead we found significant enhancement of TNF-alpha and iNOS
expression in highly-enriched astroglial cultures required the presence of 0.5-1%
microglia, respectively. Thus suggesting that microglial-astroglial interactions
are required for LPS to induce the expression of pro-inflammatory factors and
GDNF from astroglia. Specifically, we found that microglia-derived TNF-alpha
plays a pivotal role as a paracrine signal to regulate the neuroprotective
functions of astrogliosis. Taken together, these findings suggest that astroglia
may not possess the ability to directly recognize the innate immune stimuli LPS,
but rather depend on crosstalk with microglia to elicit release of neurotrophic
factors as a counterbalance to support neuronal survival from the collateral
damage generated by activated microglia during neuroinflammation.
PMID- 25130276
TI - Prenatal testosterone of progenitors could be involved in the etiology of both
anorexia nervosa and autism spectrum disorders of their offspring.
AB - OBJECTIVES: High intrauterine testosterone (T) levels seem to play a role in the
development of autism spectrum disorders (ASDs), but their role in anorexia
nervosa (AN) is controversial. Parents with masculinized 2D:4D ratios, a marker
of the organizational effects of T, may have other relevant biological
characteristics, in particular exposing their offspring to high T levels in the
prenatal environment. This would increase the likelihood of their offspring
developing these disorders. METHODS: The present study examined whether parents
of offspring with AN (n=34; mean age= 51) and ASD (n=36; mean age=45) differ from
control parents (n=40; mean age=43) in 2D:4D ratio, as well as by salivary T
levels and its relationships. RESULTS: Our results revealed that AN and ASD
parents (fathers and mothers) have masculinized 2D:4D ratios of the right hand
compared to control parents. However, the difference compared to controls was
larger in the ASD than the AN group. Furthermore, current salivary T levels were
negatively related to the 2D:4D ratio in ASD and AN parents only. CONCLUSIONS:
Our data partially support the view of high prenatal masculinization as a
potential intermediate phenotype to the development of these disorders in their
offspring.
PMID- 25130277
TI - Abiotic stress tolerance and competition-related traits underlie phylogenetic
clustering in soil bacterial communities.
AB - Soil bacteria typically coexist with close relatives generating widespread
phylogenetic clustering. This has been ascribed to the abiotic filtering of
organisms with shared ecological tolerances. Recent theoretical developments
suggest that competition can also explain the phylogenetic similarity of
coexisting organisms by excluding large low-competitive clades. We propose that
combining the environmental patterns of traits associated with abiotic stress
tolerances or competitive abilities with phylogeny and abundance data, can help
discern between abiotic and biotic mechanisms underlying the coexistence of
phylogenetically related bacteria. We applied this framework in a model system
composed of interspersed habitats of highly contrasted productivity and
comparatively dominated by biotic and abiotic processes, i.e. the plant patch-gap
mosaic typical of drylands. We examined the distribution of 15 traits and 3290
bacterial taxa in 28 plots. Communities showed a marked functional response to
the environment. Conserved traits related to environmental stress tolerance (e.g.
desiccation, formation of resistant structures) were differentially selected in
either habitat, while competition related traits (e.g. organic C consumption,
formation of nutrient-scavenging structures) prevailed under high resource
availability. Phylogenetic clustering was stronger in habitats dominated by
biotic filtering, suggesting that competitive exclusion of large clades might
underlie the ecological similarity of co-occurring soil bacteria.
PMID- 25130278
TI - Association between binge eating and attention-deficit/hyperactivity disorder in
two pediatric community mental health clinics.
AB - OBJECTIVE: Attention-Deficit/ Hyperactivity Disorder (ADHD) has been linked with
obesity; however its relationship with binge eating (BE) is less clear. We aimed
to explore the associations among ADHD, weight, and BE in pediatric mental health
clinics. METHOD: We retrospectively reviewed consecutive intakes in two pediatric
mental health clinics (N = 252). BE was assessed using the C-BEDS scale.
Associations between ADHD, BE, and BMI-z score were assessed via regression.
RESULTS: Mean age was 10.8 (3.7 SD) years. Twelve percent (n = 31) had BE. The
association between ADHD and BE was statistically significant (OR 16.1, p <
.001), and persisted after adjusting for comorbid diagnoses, medications,
demographic variables, and clinic. There was a statistically significant
association between ADHD and BMI z-scores (beta = 0.54, p < .001). After
adjusting for BE, the relationship between ADHD and BMI z-scores was attenuated
(beta = 0.35, p = .025), and the coefficient for BE was decreased (beta = 0.75, p
= .001). Although stimulant use was associated with a three-fold increase in odds
of BE (OR 3.16, p = .006), stimulants were not associated with greater BMI-z
scores (beta = 0.18, p = .32). DISCUSSION: There was a significant association
between ADHD and BE in two pediatric mental health clinics. Although these data
are cross-sectional, and cannot be used to make causal inferences, these findings
are compatible with the hypothesis that BE partially mediates the association
between ADHD and BMI z-scores. In mental health clinics, children with ADHD may
present as overweight or obese. Further, children with ADHD may exhibit BE.
Future prospective studies should elucidate the complex relationships among ADHD,
weight, stimulants, and BE.
PMID- 25130279
TI - Appropriateness of the definition of 'sedentary' in young children: Whole-room
calorimetry study.
AB - OBJECTIVES: The present study aimed to measure the energy cost of three common
sedentary activities in young children to test whether energy expended was
consistent with the recent consensus definition of 'sedentary' as 'any behaviour
conducted in a sitting or reclining posture and with an energy cost <= 1.5
metabolic equivalents (METs)' (Sedentary Behaviour Research Network, 2012).
DESIGN: Observational study. METHODS: Whole-room calorimetry measures of
television viewing, sitting at a table drawing and reading, and sitting on the
floor playing with toys were made in 40 young children (mean age 5.3 years, SD
1.0). RESULTS: The energy cost of each sedentary activity was consistent with the
recent consensus definition of sedentary: 1.17 METs (95% CI 1.07-1.27) for TV
viewing; 1.38 METs (95% CI 1.30-1.46) for sitting at a table; and 1.35 METs (95%
CI 1.28-1.43) for floor-based play. CONCLUSIONS: Common sedentary activities in
young children have energy costs which are consistent with the recent consensus
definition of 'sedentary', and the present study is supportive of this
definition.
PMID- 25130280
TI - The relationship between clinically measured hip rotational motion and shoulder
biomechanics during the pitching motion.
AB - OBJECTIVES: To examine how clinically measured hip motion is related to shoulder
biomechanics during the pitching motion. DESIGN: Cross-sectional. METHODS:
Bilateral hip rotational range of motion was measured clinically among 34
collegiate baseball pitchers. External rotation torque and maximum horizontal
adduction range of motion of the throwing shoulder were measured using a three
dimensional, high speed video capture system. RESULTS: Separate standard multiple
regression analyses showed that the total hip rotational range of motion of the
lead leg had a significant relationship with shoulder external rotation torque
during the throwing motion (r=0.56, P=0.003). Both lead leg hip external rotation
range of motion (r=-0.39, P=0.02) and internal rotation range of motion (r=0.42,
P=0.009) made significant contributions to this dependent variable. Lead leg
external rotation range of motion also had a significant negative relationship
with shoulder horizontal adduction range of motion (r=-0.36, P=0.04). The total
rotational range of motion of the trail leg had a significant relationship with
shoulder horizontal adduction range of motion (r=0.43, P=0.04). However, trail
leg external rotation range of motion was the only significant contributor to
this relationship (r=-0.35, P=0.04). No other significant relationships were
noted (r<0.37, P>0.11). CONCLUSIONS: Our results demonstrate that altered hip
rotational range of motion, measured clinically, has a direct effect on the
amount of external rotation torque and horizontal adduction range of motion of
the shoulder during the throwing motion.
PMID- 25130282
TI - The effects of serotonin1A receptor on female mice body weight and food intake
are associated with the differential expression of hypothalamic neuropeptides and
the GABAA receptor.
AB - Both common eating disorders anorexia nervosa and bulimia nervosa are
characteristically diseases of women. To characterize the role of the 5-HT1A
receptor (5-HT1A-R) in these eating disorders in females, we investigated the
effect of saline or 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) treatment
on feeding behavior and body weight in adult WT female mice and in adult 5-HT1A-R
knockout (KO) female mice. Our results showed that KO female mice have lower food
intake and body weight than WT female mice. Administration of 8-OH-DPAT decreased
food intake but not body weight in WT female mice. Furthermore, qRT-PCR was
employed to analyze the expression levels of neuropeptides, gamma-aminobutyric
acid A receptor subunit beta (GABAA beta subunits) and glutamic acid
decarboxylase in the hypothalamic area. The results showed the difference in food
intake between WT and KO mice was accompanied by differential expression of POMC,
CART and GABAA beta2, and the difference in body weight between WT and KO mice
was associated with significantly different expression levels of CART and GABAA
beta2. As such, our data provide new insight into the role of 5-HT1A-R in both
feeding behavior and the associated expression of neuropeptides and the GABAA
receptor.
PMID- 25130283
TI - Phenylboronate chromatography selectively separates glycoproteins through the
manipulation of electrostatic, charge transfer, and cis-diol interactions.
AB - Phenylboronate chromatography (PBC) has been applied for several years, however
details regarding the mechanisms of interactions between the ligand and
biomolecules are still scarce. The goal of this work is to investigate the
various chemical interactions between proteins and their ligands, using a protein
library containing both glycosylated and nonglycosylated proteins. Differences in
the adsorption of these proteins over a pH range from 4 to 9 were related to two
main properties: charge and presence of glycans. Acidic or neutral proteins were
strongly adsorbed below pH 8 although the uncharged trigonal form of
phenylboronate (PB) is less susceptible to forming electrostatic and cis-diol
interactions with proteins. The glycosylated proteins were only adsorbed above pH
8 when the electrostatic repulsion between the boronate anion and the protein
surface was mitigated (at 200 mM NaCl). All basic proteins were highly adsorbed
above pH 8 with PB also acting as a cation-exchanger with binding occurring
through electrostatic interactions. Batch adsorption performed at acidic
conditions in the presence of Lewis base showed that charge-transfer interactions
are critical for protein retention. This study demonstrates the multimodal
interaction of PBC, which can be a selective tool for separation of different
classes of proteins.
PMID- 25130284
TI - Authors' response to letter by Ritzen et al. (Published online 25 July 2014, DOI:
10.1111/cen.12531).
PMID- 25130281
TI - Results of a randomized, double-blind, parallel-group, placebo- and active
controlled, multicenter study of mirabegron, a beta3-adrenoceptor agonist, in
patients with overactive bladder in Asia.
AB - AIMS: To assess the efficacy and safety of mirabegron 50 mg once daily compared
with placebo and the active control, tolterodine extended-release (ER) 4 mg once
daily, in patients with symptoms of overactive bladder (OAB) in Taiwan, Korea,
China, and India. METHODS: A 12-week multinational, randomized, double-blind,
parallel-group placebo- and active-controlled trial. The primary efficacy
endpoint was change from baseline to final visit in mean number of
micturitions/24 hr. Secondary endpoints were: mean number of urgency episodes,
incontinence episodes and urge incontinence episodes/24 hr, mean number of
nocturia episodes per night, mean volume voided per micturition, and quality-of
life (QoL) scores as assessed by the King's Health Questionnaire (KHQ). RESULTS:
Of 1,126 patients who were randomized to receive double-blind study drug, 921
patients (300, 311, and 310 in the placebo, mirabegron 50 mg, and tolterodine ER
4 mg groups, respectively) completed the treatment period. Demographic
characteristics were similar across treatment groups. A statistically significant
improvement versus placebo in mean number of micturitions/24 hr was seen with
mirabegron 50 mg at all timepoints (P < 0.05) as well as final visit (-0.57 with
95% confidence intervals [CIs] of [-1.04, -0.09], P = 0.019). There was no
significant difference between treatment groups in improvement from baseline to
final visit in any of the secondary outcome measures except volume voided per
micturition. The overall incidence of drug-related adverse events was 17.2%,
15.8%, and 21.3%, in the placebo, mirabegron 50 mg, and tolterodine ER 4 mg
groups, respectively. CONCLUSIONS: Mirabegron 50 mg once daily for 12 weeks was
superior to placebo in reducing the frequency of micturitions in patients with
symptoms of OAB in Taiwan, Korea, China, and India.
PMID- 25130285
TI - Inability of Turbidimetry Method in Detecting Glycated Hemoglobin to Select
Diabetes Mellitus Patients According to Their Concentrations of Blood Glucose
Levels.
AB - BACKGROUND: Diabetes mellitus is a chronicle illness in which there is a high
blood glucose level defined as hyperglycemia, resulted by a deficiency in insulin
secretion and/or in its action. Nowadays, it is being seen as a public health
problem and is reaching increasing proportions with regard to the appearance of
new cases. For diagnosis, sensible and accurate methods should be used to avoid
complications of the sickness. The measure of glycated hemoglobin may not be used
for diagnosis, but is the reference method to evaluate the grade of glycemic
control in the long term, reflecting the blood glucose level in the latest 2-3
months. The aim of this study was to evaluate the grade of concordance between
turbidimetry and liquid chromatography methods in the glycated hemoglobin
determination and to estimate the sensibility and specificity values of
turbidimetry. METHODS: This study included 133 blood samples obtained from
patients and healthy donors, ageing between 18 and 80 years with glycemic values
between 58 and 473 mg/dl. RESULTS AND CONCLUSION: Turbidimetry is a useful method
for determining glycemic levels above 100 and over 200 mg/dl, but does not have
the ability to select samples with intermediary blood glucose concentrations.
PMID- 25130286
TI - Ontogenetic cell death and phagocytosis in the visual system of vertebrates.
AB - Programmed cell death (PCD), together with cell proliferation, cell migration,
and cell differentiation, is an essential process during development of the
vertebrate nervous system. The visual system has been an excellent model on which
to investigate the mechanisms involved in ontogenetic cell death. Several phases
of PCD have been reported to occur during visual system ontogeny. During these
phases, comparative analyses demonstrate that dying cells show similar but not
identical spatiotemporally restricted patterns in different vertebrates.
Additionally, the chronotopographical coincidence of PCD with the entry of
specialized phagocytes in some regions of the developing vertebrate visual system
suggests that factors released from degenerating cells are involved in the cell
migration of macrophages and microglial cells. Contradicting this hypothesis
however, in many cases the cell corpses generated during degeneration are rapidly
phagocytosed by neighboring cells, such as neuroepithelial cells or Muller cells.
In this review, we describe the occurrence and the sites of PCD during the
morphogenesis and differentiation of the retina and optic pathways of different
vertebrates, and discuss the possible relationship between PCD and phagocytes
during ontogeny.
PMID- 25130288
TI - Morphological properties of the last primaries, the tail feathers, and the alulae
of Accipiter nisus, Columba livia, Falco peregrinus, and Falco tinnunculus.
AB - We investigated the mechanical properties (Young's modulus, bending stiffness,
barb separation forces) of the tenth primary of the wings, of the alulae and of
the middle tail feathers of Falco peregrinus. For comparison, we also
investigated the corresponding feathers in pigeons (Columba livia), kestrels
(Falco tinnunculus), and sparrowhawks (Accipiter nisus). In all four species, the
Young's moduli of the feathers ranged from 5.9 to 8.4 GPa. The feather shafts of
F. peregrinus had the largest cross-sections and the highest specific bending
stiffness. When normalized with respect to body mass, the specific bending
stiffness of primary number 10 was highest in F. tinnunculus, while that of the
alula was highest in A. nisus. In comparison, the specific bending stiffness,
measured at the base of the tail feathers and in dorso-ventral bending direction,
was much higher in F. peregrinus than in the other three species. This seems to
correlate with the flight styles of the birds: F. tinnunculus hovers and its
primaries might therefore withstand large mechanical forces. A. nisus has often
to change its flight directions during hunting and perhaps needs its alulae for
this maneuvers, and in F. peregrinus, the base of the tail feathers might need a
high stiffness during breaking after diving.
PMID- 25130287
TI - Diagnosing and following adult patients with acute myeloid leukaemia in the
genomic age.
AB - The diagnosis and follow-up process of adult patients with acute myeloid
leukaemia (AML) is challenging to clinicians and laboratory staff alike. While
several sets of recommendations have been published over the years, the
development of high throughput screening and characterization for both genetic
and epigenetic events have evolved with astonishing speed. Here we attempt to
provide a practical guide to diagnose and follow adult AML patients with a focus
on how to balance the wealth of information on the one hand, with the restriction
put on these processes in terms of time, feasibility and economy when caring for
these patients, on the other.
PMID- 25130289
TI - A randomized trial of cefozopran versus cefepime as empirical antibiotic
treatment of febrile neutropenia in pediatric cancer patients.
AB - BACKGROUND: Febrile neutropenia (FN) is a common and serious complication of
cancer chemotherapy associated with significant morbidity and mortality.
Cefozopran (CZOP) is a potential candidate for empirical monotherapy in FN.
However, studies on the use of CZOP as empirical treatment for pediatric patients
with FN are quite limited. The purpose of this study was to compare the efficacy
and safety of CZOP with cefepime (CFPM) empirical monotherapy in pediatric cancer
patients with FN. PROCEDURES: A total of 64 patients with 224 episodes of FN were
randomly assigned to receive antibiotic therapy with either CZOP (100 mg/kg/day)
or CFPM (100 mg/kg/day). Of these episodes, 223 were considered eligible for the
study. Success was defined as resolution of febrile episodes and clinical signs
of infection within 120 hr following the start of antibiotic therapy. RESULTS:
The success rate was not significantly different between the CZOP (64.0%) and
CFPM (56.3%) groups (P = 0.275). Duration of fever, duration of antibiotic
therapy, and the success rate in patients with blood stream infection did not
differ between the two groups. There was no infection-related mortality in the
study period. CONCLUSION: Both CZOP and CFPM as monotherapy appear to be
effective and safe in pediatric patients. This study suggests that CZOP has
satisfactory efficacy and is well tolerated as initial empirical therapy for
pediatric cancer patients with FN.
PMID- 25130290
TI - Screening for obstructive sleep apnea in children with syndromic cleft lip and/or
palate.
AB - BACKGROUND: Craniofacial malformations including cleft lip and/or palate (CL/P)
increase risk for obstructive sleep apnea (OSA). While 30% of CL/P occurs in the
context of underlying genetic syndromes, few studies have investigated the
prevalence of OSA in this high-risk group. This study aims to determine the
incidence and risk factors of positive screening for OSA in this complex patient
population. METHODS: The Pediatric Sleep Questionnaire (PSQ) was prospectively
administered to all patients cared for by the cleft lip and palate clinic at the
Children's Hospital of Philadelphia between January 2011 and August 2013. The PSQ
is a 22-item, validated screening tool for OSA with a sensitivity and specificity
of 0.83 and 0.87 in detecting an apnea-hypopnea index (AHI) >5/hour in healthy
children. The Fisher exact and Chi-square tests were used for purposes of
comparison. RESULTS: 178 patients with syndromic CL/P completed the PSQ. Mean
cohort age was 8.1 +/- 4.4 years. Patients were predominately female (53.9%),
Caucasian (78.1%), and had Veau Class II cleft (50.6%). Craniofacial syndromes
included isolated Pierre Robin Sequence (PRS) (29.8%), 22q11.2 deletion syndrome
(14.6%), Van der Woude syndrome (6.7%), and other rare genetic abnormalities
(28.8%). The overall incidence of positive OSA screening was 32.0%. Males were at
increased risk for positive OSA screening (P = 0.030), as were non-Caucasians (P
= 0.044). Symptoms with the highest positive predictive value for OSA were
"others comment on child appearing sleepy" (76.2%) and "stops breathing during
the night" (75.0%). Notably, patients with 22q11.2 deletion syndrome were at
highest risk for positive screens (50.0%, P = 0.042). CONCLUSIONS: Nearly a third
of our patients with syndromic CL/P screened positively for OSA (32.0%),
highlighting the importance of screening in this at-risk population. Future work
will correlate screening results with polysomnograms to help validate these
findings. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, III.
PMID- 25130291
TI - Customized negative pressure wound therapy for intractable auricular defects
using alginate dressings and feeding tubes.
PMID- 25130292
TI - Variations in 30-day hospital readmission rates across primary care clinics
within a tertiary referral center.
AB - BACKGROUND: Reducing hospital readmissions is a national healthcare priority.
Little is known about how readmission rates vary across unique primary care
practices. OBJECTIVE: To calculate all-cause 30-day hospital readmission rates at
the level of individual primary care practices and identify factors associated
with variations in these rates. DESIGN: Retrospective analysis SETTING: Seven
primary care clinics affiliated with the University of California, San Francisco
(UCSF). PATIENTS: Adults >=18 years old with a primary care provider (PCP) at
UCSF MEASUREMENTS: All-cause 30-day readmission rates were calculated for primary
care clinics for discharges between July 1, 2009 and June 30, 2012. We built a
model to identify demographic, clinical, and hospital factors associated with
variation in rates. RESULTS: There were 12,564 discharges for patients belonging
to the 7 clinics, with 8685 index discharges and 1032 readmissions. Readmission
rates varied across practices, from 14.9% in Human Immunodeficiency Virus primary
care and 7.7% in women's health. In multivariable analyses, factors associated
with variation in readmission rates included: male gender (odds ratio [OR]: 1.21,
95% confidence interval [CI]: 1.05-1.40), Medicare insurance (OR: 1.31, 95% CI:
1.05, 1.64; Ref = private), Medicare-Medicaid dual eligible (OR: 1.26, 95% CI:
1.01-1.56), multiple comorbidities, and admitting services. Patients with a
departed PCP awaiting transfer assignment to a new PCP had an OR of 1.59 (95% CI:
1.16-2.17) compared with having a current faculty PCP. CONCLUSIONS: Primary care
practices are important partners in improving care transitions and reducing
hospital readmissions, and this study introduces a new way to view readmission
rates. PCP turnover may be an important risk factor for hospital readmissions.
PMID- 25130293
TI - Long-term efficacy, safety, and side effect profile of botulinum toxin in
dystonia: a 20-year follow-up.
AB - Most long-term studies of the efficacy and safety profile of botulinum toxin
(BoNT) in the treatment of dystonia are limited by lack of objective assessments,
relatively small sample size, or short follow-up periods. We present one of the
longest follow-up studies of BoNT treatment. This is a retrospective,
longitudinal study that analyzes data on 89 patients treated with BoNT for
dystonia at our Movement Disorders Clinic for up to 26 years (mean follow-up
period of 18.5 years). The mean ages at the time of the first and last injections
were 49 and 68 years old, respectively. The most common diagnoses were cervical
dystonia (N = 51), blepharospasm (N = 34), and oromandibular dystonia (N = 26).
The total number of onabotulinumtoxinA units received during the first injection
was 140.3 as compared to 224.5 at the last injection (p < 0.0001). The global
response effect was 3.18 after the first injection session and 3.57 after the
last injection (p < 0.0001). The duration of response after the initial injection
session and at the last injection was 16.33 weeks versus 19.42 weeks (p 0.0037),
respectively. Adverse events, typically related to injection site, were reported
in 19% of the visits. This series of dystonia patients with the longest reported
treatment with BoNT provide evidence that in selected patients repeated
chemodenervation is associated with sustained symptomatic benefit, decreased
latency effect, and prolonged duration of therapeutic response. Despite the
higher requirement of mean units per visit over time, only 19% of all treatment
cycles are associated with adverse, but tolerable, side effects.
PMID- 25130294
TI - Qualitative and spatial metabolite profiling of lichens by a LC-MS approach
combined with optimised extraction.
AB - INTRODUCTION: Lichens are self-sustaining partnerships comprising fungi as shape
forming partners for their enclosed symbiotic algae. They produce a tremendous
diversity of metabolites (1050 metabolites described so far). OBJECTIVES: A
comparison of metabolic profiles in nine lichen species belonging to three genera
(Lichina, Collema and Roccella) by using an optimised extraction protocol,
determination of the fragmentation pathway and the in situ localisation for major
compounds in Roccella species. METHODS: Chemical analysis was performed using a
complementary study combining a Taguchi experimental design with qualitative
analysis by high-performance liquid chromatography coupled with mass spectrometry
techniques. RESULTS: Optimal conditions to obtain the best total extraction yield
were determined as follows: mortar grinding to a fine powder, two successive
extractions, solid:liquid ratio (2:60) and 700 rpm stirring. Qualitative analysis
of the metabolite profiling of these nine species extracted with the optimised
method was corroborated using MS and MS/MS approaches. Nine main compounds were
identified: 1 beta-orcinol, 2 orsellinic acid, 3 putative choline sulphate, 4
roccellic acid, 5 montagnetol, 6 lecanoric acid, 7 erythrin, 8 lepraric acid and
9 acetylportentol, and several other compounds were reported. Identification was
performed using the m/z ratio, fragmentation pathway and/or after isolation by
NMR analysis. The variation of the metabolite profile in differently organised
parts of two Roccella species suggests a specific role of major compounds in
developmental stages of this symbiotic association. CONCLUSION: Metabolic
profiles represent specific chemical species and depend on the extraction
conditions, the kind of the photobiont partner and the in situ localisation of
major compounds.
PMID- 25130295
TI - IL-12-and IL-23 in health and disease.
AB - Interleukin (IL)-12 and IL-23 play important roles in the development of
experimental autoimmune disease models and numerous afflictions affecting humans.
Preclinical data over the last 20 years combined with successful clinical trials
has identified a clear relationship between IL-12, IL-23 and the generation of
pathogenic T helper cells capable of orchestrating tissue inflammation.
Observations made in the clinic have shown that IL-12p40, a common subunit shared
by IL-12 and IL-23, is critical to pathologies associated with psoriasis,
inflammatory bowel disease (IBD) and tumor growth. These advancements have set in
motion the development of a number of potential therapeutics aimed at
manipulating IL-12/23 signaling pathways in both mice and humans. This review
will discuss a brief history of the understanding and expansion of the IL-12
cytokine family, some difficulties associated with preclinical data
interpretation and finally the medicinal interventions that have been developed
to combat IL-12/23-driven autoimmune disorders.
PMID- 25130296
TI - Exploiting differential expression of the IL-7 receptor on memory T cells to
modulate immune responses.
AB - Interleukin-7 is a non-redundant growth, differentiation and survival factor for
human T lymphocytes. Most circulating, mature T cells express the receptor for IL
7, but not all. Importantly, CD4 Tregs express greatly reduced levels of IL-7R
compared to conventional CD4 T cells, presenting an opportunity to selectively
target the latter cells with either more IL-7 to boost responses, or to block IL
7 signalling to limit responses. This article reviews what is known about
regulation of IL-7R expression, and recent progress in therapeutic approaches
related to IL-7 and its receptor.
PMID- 25130298
TI - AFM images of the dark biocidal action of cationic conjugated polyelectrolytes
and oligomers on Escherichia coli.
AB - Polymers and oligomers with conjugated phenylene ethynylene or thiophene
ethynylene backbones have been shown to be potent antimicrobials. The mechanisms
by which they act have been unclear, though AFM imaging of Escherichia coli cells
before and after exposure to two such biocides, PPE-Th polymer and EO-OPE-1(C3),
shows their effects on cell surface structure. Dried, unexposed E. coli cells
could be imaged at resolution high enough to discern the physical structure of
the cell surfaces, including individual porin proteins and their distribution on
the cell. Exposure to 30 MUg/mL PPE-Th polymer caused major cell surface
disruption due to either emulsification of the outer membrane or the formation of
polymer aggregates or both. In contrast, exposure to 30 MUg/mL EO-OPE-1(C3)
oligomer did not cause large-scale membrane disruption but did cause apparent
reorganization of the surface proteins into linear arrays or protein-lipid-OPE
complexes that dominate on a small scale. E. coli cells were also successfully
imaged underwater, allowing a real-time AFM image series as cells were exposed to
30 MUg/mL EO-OPE-1(C3). Solution exposure caused the cell surfaces to noticeably
increase their roughness over time. These results agree with proposed mechanisms
for cell killing by PPE-Th and EO-OPE-1(C3) put forth by Wang et al.1 in which
PPE-Th kills by large-scale disruption of the outer membrane and EO-OPE-1(C3)
kills by membrane reorganization with possible pore formation.
PMID- 25130297
TI - A randomized controlled clinical trial of levofloxacin 750 mg versus 500 mg
intravenous infusion in the treatment of community-acquired pneumonia.
AB - The objective of this study was to compare the efficacy and safety of
levofloxacin 750 mg for 5 days versus 500 mg for 7-14 days intravenous (IV) in
the treatment of community-acquired pneumonia (CAP). This clinical trial was the
first of its kind conducted in Chinese people and also in Asian population. A
total of 241 were enrolled and randomized to 750 mg group (n = 121) or 500 mg (n
= 120) group from 10 study centers. The median treatment duration was 5.0 days in
750 mg and 9.0 days in 500 mg group. The median total dose was 3750 mg in 750 mg
and 4500 mg in 500 mg group. The bacterial eradication rate was 100% in both
groups. The overall efficacy rate in 750 mg group was 86.2% (94/109), and 84.7%
(94/111), in 500 mg group of full analysis set visit 4, 95% confidence interval
of 1.6% (-7.8-10.9%); the statistical results showed that 750 mg group was non
inferior to 500 mg group. The most common clinical adverse drug reactions were
injection site adverse reactions in both 750 mg group and 500 mg group; the other
common adverse drug reactions were insomnia, nausea, skin rash, etc. The most
common drug-related laboratory abnormalities were neutrophil percentage
decreased, decreased white blood cell count, alanine aminotransferase, and
aspartate aminotransferase elevation in both 750 mg group and 500 mg group. Most
of adverse drug reactions were mild in severity and well-tolerated. In summary,
the regimen of levofloxacin 750 mg IV for 5 days was at least as effective and
well tolerated as 500 mg IV for 7-14 days for the treatment of CAP.
PMID- 25130299
TI - Rats' choices with token stimuli in concurrent variable-interval schedules.
AB - Four rats responded on concurrent variable-interval schedules that delivered
token stimuli (stimulus lights arranged vertically above each of two side
levers). During exchange periods, each token could be exchanged for one food
pellet by responding on a center lever, with one response required for each
pellet delivery. In different conditions, the exchange requirements (number of
tokens that had to be earned before they could be exchanged for food) varied
between one and four for the two response levers. The experiments were closely
patterned after research with pigeons by Mazur and Biondi (2013), and the results
from the rats in the present experiment were similar. Response percentages on the
two levers changed as each additional token was earned, and these patterns
indicated that choice was controlled by both the time to the exchange periods and
the number of food pellets that were delivered in the exchange period. In some
conditions, the exchange requirement was three tokens for each lever, but the
token lights were not turned on as they were earned for one of the two keys. The
rats showed a slight preference for the lever without the token lights, which may
indicate that the token lights were not serving as conditioned reinforcers (a
result also found by Mazur and Biondi with pigeons). Overall, these results
suggest that, in this choice procedure, the token stimuli served primarily as
discriminative stimuli that signaled the temporal proximity and quantity of the
primary reinforcer, food.
PMID- 25130300
TI - The association between secondhand smoke and sleep-disordered breathing in
children: a systematic review.
AB - OBJECTIVE: To systematically review existing literature on the association
between secondhand smoke and sleep-disordered breathing in children. DATA
SOURCES: PubMed, Embase, Cochrane CENTRAL, Web of Science, and Scopus. REVIEW
METHODS: Inclusion criteria included English-language papers containing original
human data, with seven or more subjects and age <18 years. Data were
systematically collected on study design, patient demographics, clinical
characteristics/outcomes, and level of evidence. Two investigators independently
reviewed all manuscripts. RESULTS: The initial search yielded 72 abstracts; 18
articles were ultimately included with a total study population of 47,462
patients. Fifteen (83%) articles found a statistically significant association
between secondhand smoke and sleep-disordered breathing. All were case-control
studies. Quality of articles based on the Newcastle-Ottawa scale averaged 5.8/9
stars. Secondhand smoke was characterized by serum cotinine testing in only two
(11%) studies. Sleep-disordered breathing was quantified by polysomnography in
only four (22%) of the studies and only one (6%) classified subject using
polysomnography exclusively. Habitual snoring was the most common form of sleep
disordered breathing studied in 14/18 (78%) studies, whereas obstructive sleep
apnea was reported in one (6%) study and sleep-related hypoxia in another (6%)
study. CONCLUSIONS: Although the majority of studies included in this review
found a significant association between secondhand smoke and sleep-disordered
breathing, all of them were evidence level 3b, for an overall grade of B (Oxford
Centre for Evidence-based Medicine). Further higher-quality studies should be
performed in the future to better evaluate the relationship between second- smoke
and sleep-disordered breathing in children.
PMID- 25130302
TI - Identification of a developmentally-regulated and psychostimulant-inducible novel
rat gene mrt3 in the neocortex.
AB - The psychotomimetic effects of stimulant drugs including amphetamines and cocaine
are known to change during the postnatal development in humans and experimental
animals. To obtain an insight into the molecular basis of the onset of stimulant
induced psychosis, we have explored the gene transcripts that differentially
respond to methamphetamine (MAP) in the developing rat brains using a
differential cloning technique, the RNA arbitrarily-primed PCR. We identified
from the rat neocortex a novel and developmentally regulated MAP-inducible gene
mrt3 (MAP responsive transcript 3) that is transcribed to a presumable non-coding
RNA of 3.8kb and is located on the reverse strand of the F-box/LRR-repeat protein
17-like gene mapped on the rat chromosome Xq12. The mrt3 mRNAs are predominantly
expressed in the brain and lung. Acute MAP injection upregulated the mrt3
expression in the neocortex at postnatal day 50, but not days 8, 15 and 23, in a
D1 receptor antagonist-sensitive manner. This upregulation was mimicked by
another stimulant, cocaine, whereas pentobarbital and D1 antagonist failed to
alter the mrt3 expression. Moreover, repeated treatment with MAP for 5 days
inhibited the ability of the challenge dose of MAP or cocaine to increase the
neocortical mrt3 expression without affecting the basal mrt3 mRNA levels on day
14 of withdrawal. These late-developing, cocaine-cross reactive, D1 antagonist
sensitive and long-term regulations of mrt3 by MAP are similar to those of
stimulant-induced behavioral sensitization, a model of the onset and relapse of
stimulant-induced psychosis and schizophrenia, and therefore may be associated
with the pathophysiology of the model.
PMID- 25130303
TI - N-acetyl-aspartate (NAA) as a correlate of pharmacological treatment in
psychiatric disorders: a systematic review.
AB - The amino-acid N-acetyl-aspartate (NAA) is located in neurons and the
concentration of NAA correlates with neuronal mitochondrial function. The signal
of NAA, as measured with proton magnetic resonance spectroscopy (1H-MRS), is
considered to reflect both, neuronal density and integrity of neuronal
mitochondria. A reduction of the NAA concentrations has been found in several
psychiatric disorders. Newer studies report reversal of decreased NAA
concentration with treatment. The objective of this review is to summarize the
literature on NAA changes in association with psychopharmacological treatment in
psychiatric disorders (affective disorders, obsessive-compulsive disorder,
schizophrenia and dementia). The majority of studies identified increased NAA
concentrations in response to treatment, while a smaller number of studies did
not find this effect. The NAA increase seems to be neither specific for a certain
disorder nor for a specific intervention. This suggests that the reduction of NAA
may represent an altered functional (metabolic) state of neurons common to
different psychiatric disorders and the increase after treatment to indicate
functional restoration as one general effect of interventions.
PMID- 25130301
TI - Transcranial electrical brain stimulation modulates neuronal tuning curves in
perception of numerosity and duration.
AB - Transcranial direct current stimulation (tDCS) is a non-invasive brain
stimulation method with many putative applications and reported to effectively
modulate behaviour. However, its effects have yet to be considered at a
computational level. To address this we modelled the tuning curves underlying the
behavioural effects of stimulation in a perceptual task. Participants judged
which of the two serially presented images contained more items (numerosity
judgement task) or was presented longer (duration judgement task). During
presentation of the second image their posterior parietal cortices (PPCs) were
stimulated bilaterally with opposite polarities for 1.6s. We also examined the
impact of three stimulation conditions on behaviour: anodal right-PPC and
cathodal left-PPC (rA-lC), reverse order (lA-rC) and no-stimulation condition.
Behavioural results showed that participants were more accurate in numerosity and
duration judgement tasks when they were stimulated with lA-rC and rA-lC
stimulation conditions respectively. Simultaneously, a decrease in performance on
numerosity and duration judgement tasks was observed when the stimulation
condition favoured the other task. Thus, our results revealed a double
dissociation of laterality and task. Importantly, we were able to model the
effects of stimulation on behaviour. Our computational modelling showed that
participants' superior performance was attributable to a narrower tuning curve-
smaller standard deviation of detection noise. We believe that this approach may
prove useful in understanding the impact of brain stimulation on other cognitive
domains.
PMID- 25130304
TI - SDF-1/CXCR4 axis in Tie2-lineage cells including endothelial progenitor cells
contributes to bone fracture healing.
AB - CXC chemokine receptor 4 (CXCR4) is a specific receptor for stromal-derived
factor 1 (SDF-1). SDF-1/CXCR4 interaction is reported to play an important role
in vascular development. On the other hand, the therapeutic potential of
endothelial progenitor cells (EPCs) in fracture healing has been demonstrated
with mechanistic insight of vasculogenesis/angiogenesis and osteogenesis
enhancement at sites of fracture. The purpose of this study was to investigate
the influence of the SDF-1/CXCR4 pathway in Tie2-lineage cells (including EPCs)
in bone formation. We created CXCR4 gene conditional knockout mice using the
Cre/loxP system and set two groups of mice: Tie2-Cre(ER) CXCR4 knockout mice
(CXCR4(-/-) ) and wild-type mice (WT). We report here that in vitro, EPCs derived
from of CXCR4(-/-) mouse bone marrow demonstrated severe reduction of migration
activity and EPC colony-forming activity when compared with those derived from WT
mouse bone marrow. In vivo, radiological and morphological examinations showed
fracture healing delayed in the CXCR4(-/-) group and the relative callus area at
weeks 2 and 3 was significantly smaller in CXCR4(-/-) group mice. Quantitative
analysis of capillary density at perifracture sites also showed a significant
decrease in the CXCR4(-/-) group. Especially, CXCR4(-/-) group mice demonstrated
significant early reduction of blood flow recovery at fracture sites compared
with the WT group in laser Doppler perfusion imaging analysis. Real-time RT-PCR
analysis showed that the gene expressions of angiogenic markers (CD31, VE
cadherin, vascular endothelial growth factor [VEGF]) and osteogenic markers
(osteocalcin, collagen 1A1, bone morphogenetic protein 2 [BMP2]) were lower in
the CXCR4(-/-) group. In the gain-of-function study, the fracture in the SDF-1
intraperitoneally injected WT group healed significantly faster with enough
callus formation compared with the SDF-1 injected CXCR4(-/-) group. We
demonstrated that an EPC SDF-1/CXCR4 axis plays an important role in bone
fracture healing using Tie2-Cre(ER) CXCR4 conditional knockout mice.
PMID- 25130305
TI - What is a paternal effect?
AB - Maternal effects are now universally recognised as a form of nongenetic parental
influence on offspring but, until recently, paternal effects were regarded as an
anomaly. Although it is now clear that paternal effects are both widespread and
important, their proximate basis and evolutionary consequences have received
little attention and remain poorly understood. In particular, because many
paternal effects are mediated by maternal responses such as differential
allocation, the boundary between paternal and maternal effects is sometimes
blurred. We distinguish here three basic types of paternal effect and clarify the
role of maternal responses in these effects. We also outline key questions that
can serve as a road map for research on the proximate basis and evolutionary
implications of paternal effects.
PMID- 25130306
TI - Failure mode analysis in adrenal vein sampling: a single-center experience.
AB - PURPOSE: To analyze failure modes in a high-volume adrenal vein sampling (AVS)
practice in an effort to identify preventable causes of nondiagnostic sampling.
MATERIALS AND METHODS: A retrospective database was constructed containing 343
AVS procedures performed over a 10-year period. Each nondiagnostic AVS procedure
was reviewed for failure mode and correlated with results of any repeat AVS. Data
collected included selectivity index, lateralization index, adrenalectomy
outcomes if performed, and details of AVS procedure. All AVS procedures were
performed after cosyntropin stimulation, using sequential technique. RESULTS: AVS
was nondiagnostic in 12 of 343 (3.5%) primary procedures and 2 secondary
procedures. Failure was right-sided in 8 (57%) procedures, left-sided in 4 (29%)
procedures, bilateral in 1 procedure, and neither in 1 procedure (laboratory
error). Failure modes included diluted sample from correctly identified vein (n =
7 [50%]; 3 right and 4 left), vessel misidentified as adrenal vein (n = 3 [21%];
all right), failure to locate an adrenal vein (n = 2 [14%]; both right),
cosyntropin stimulation failure (n = 1 [7%]; diagnostic by nonstimulated
criteria), and laboratory error (n = 1 [7%]; specimen loss). A second AVS
procedure was diagnostic in three of five cases (60%), and a third AVS procedure
was diagnostic in one of one case (100%). Among the eight patients in whom AVS
ultimately was not diagnostic, four underwent adrenalectomy based on diluted AVS
samples, and one underwent adrenalectomy based on imaging; all five experienced
improvement in aldosteronism. CONCLUSIONS: A substantial percentage of AVS
failures occur on the left, all related to dilution. Even when technically
nondiagnostic per strict criteria, some "failed" AVS procedures may be sufficient
to guide therapy. Repeat AVS has a good yield.
PMID- 25130307
TI - Contemporary systematic review and meta-analysis of early outcomes with
percutaneous treatment for infrapopliteal atherosclerotic disease.
AB - PURPOSE: The need for specialty devices to improve the technical outcome of
endovascular interventions is dependent on the rate of early failure in such
procedures. This meta-analysis assessed procedural outcomes of such interventions
to elucidate the rate of early procedural failures and the need for such
specialty devices. MATERIALS AND METHODS: MEDLINE and EMBASE were searched for
contemporary studies (2000-2012) reporting procedural or short-term outcomes for
revascularization of infrapopliteal atherosclerotic lesions. A random-effects
metaanalysis was performed, which included post hoc comparisons among treatment
groups. RESULTS: A total of 42 studies with 52 treatment arms representing 3,660
unique patients were included. Technical success rates were higher with bare
metal stents (BMSs; 98.6%) than with atherectomy (92.2%; P < .05) or percutaneous
transluminal angioplasty (PTA; 91.2%; P = .01), and higher with drug-eluting
stents (DESs) than with PTA (P < .001). DES use had higher primary patency rates
than atherectomy (P < .05), BMS use (P < .001), and PTA (P < .01). The 30-day
rate of target lesion revascularization was significantly higher with PTA (8.1%)
than with BMSs (2.2%; P < .05) and DESs (1.1%; P < .05). Thirty-day rates of
major unplanned amputation (range, 1.5%-4.4%) and mortality (range, 0.9%-3.3%)
were comparable among treatment groups. Significant heterogeneity among studies
was noted for most PTA outcomes. Publication bias was evident for most PTA and
DES outcomes. CONCLUSIONS: Early failure of percutaneous therapies in patients
with infrapopliteal atherosclerotic lesions is device- and technique-dependent.
Specialty devices designed to reduce technical failure rates may therefore be of
benefit in this selected group of patients. Study results are confounded by
inconsistent data reporting, heterogeneity of treatment effects, and publication
bias.
PMID- 25130308
TI - An economic analysis of sublobar resection versus thermal ablation for early
stage non-small-cell lung cancer.
AB - PURPOSE: To compare medical costs for a matched-pair cohort of Medicare patients
with early-stage non-small-cell lung cancer (NSCLC) who underwent treatment with
sublobar resection or thermal ablation. MATERIALS AND METHODS: Patients at least
65 years of age with stage IA/IB NSCLC treated with sublobar resection or thermal
ablation from 2007 to 2009 were identified from Surveillance, Epidemiology, and
End Results/Medicare-linked data and matched by propensity scores. The primary
outcome of interest, cost from the payer's perspective, was derived from Medicare
claims data. A partitioned inverse probability-weighted estimator was used to
calculate mean and median treatment-related costs and costs at 1, 3, 12, 18, and
24 months after treatment. Baseline characteristics, Kaplan-Meier survival
curves, and calculated cost variables were compared between the two groups.
RESULTS: The final matched cohort of 128 patients had similar baseline
characteristics and overall survival (P = .52). Patients who underwent ablation
had significantly lower treatment-related costs than those who underwent sublobar
resection (P < .001). The difference in median treatment-related cost was
$16,105. At 1 month, 3 months, and 12 months after treatment, cumulative costs
remained significantly different (P <= .011). Lower cost associated with
ablations performed in the outpatient setting was a major contributor to the
differences between the two treatment modalities, although inpatient ablations
maintained a small cost advantage over sublobar resections. CONCLUSIONS: Among
matched Medicare patients with stage I NSCLC, thermal ablation resulted in
significantly lower treatment-related costs and cumulative medical costs 1 month,
3 months, and 12 months after treatment compared with sublobar resection.
PMID- 25130309
TI - Reply: To PMID 24913549.
PMID- 25130310
TI - Understanding the complex needs of automotive training at final assembly lines.
AB - Automobile final assembly operators must be highly skilled to succeed in a low
automation environment where multiple variants must be assembled in quick
succession. This paper presents formal user studies conducted at OPEL and VOLVO
Group to identify assembly training needs and a subset of requirements; and to
explore potential features of a hypothetical game-based virtual training system.
Stakeholder analysis, timeline analysis, link analysis, Hierarchical Task
Analysis and thematic content analysis were used to analyse the results of
interviews with various stakeholders (17 and 28 participants at OPEL and VOLVO,
respectively). The results show that there is a strong case for the
implementation of virtual training for assembly tasks. However, it was also
revealed that stakeholders would prefer to use a virtual training to complement,
rather than replace, training on pre-series vehicles.
PMID- 25130311
TI - Assessment model for perceived visual complexity of automotive instrument
cluster.
AB - This research proposes an assessment model for quantifying the perceived visual
complexity (PVC) of an in-vehicle instrument cluster. An initial study was
conducted to investigate the possibility of evaluating the PVC of an in-vehicle
instrument cluster by estimating and analyzing the complexity of its individual
components. However, this approach was only partially successful, because it did
not take into account the combination of the different components with random
levels of complexity to form one visual display. Therefore, a second study was
conducted focusing on the effect of combining the different components. The
results from the overall research enabled us to suggest a basis for quantifying
the PVC of an in-vehicle instrument cluster based both on the PVCs of its
components and on the integration effect.
PMID- 25130312
TI - Cisplatin-induced testicular toxicity in rats: the protective effect of arjunolic
acid.
AB - In the present study, the effect of arjunolic acid on testicular damage induced
by intraperitoneal injection of rats with 7 mg/kg cisplatin was studied.
Cisplatin induced a significant reduction in testicular weights, plasma
testosterone, and testicular reduced glutathione levels in addition to a
significant elevation of testicular malondialdehyde levels and testicular gene
expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor
alpha (TNF-alpha), and p38 mitogen-activated protein kinase (MAPK) when compared
with the control group (p < 0.05). Lower tubular diameters and depletion of germ
cells and irregular small seminiferous tubules with Sertoli cells only were
observed in the cisplatin group. Arjunolic acid administration significantly
corrected the changes in both biochemical and histopathological parameters.
Arjunolic acid plays a significant protective role against cisplatin-induced
testicular injury by attenuating oxidative stress parameters along with
downregulation of iNOS, TNF-alpha, and p38-MAPK testicular expressions.
PMID- 25130313
TI - Sensory modality-specific spatio-temporal dynamics in response to counting tasks.
AB - From perception to behavior, the human brain processes information in a flexible
and abstract manner independent of an input sensory modality. However, the
mechanism of such multisensory neural information processing in the brain remains
under debate. Relatedly, studies often aim to investigate whether certain brain
regions behave in a modality-specific manner or invariantly. Previous studies
regarding multisensory information processing have commonly reported only on the
activation of brain regions in response to unimodal or multimodal sensory
stimuli. However, less attention has been given to the modality effect on the
dynamics of such regions, which could advance our understanding of neuronal
information processing. In this study, we investigated whether brain regions show
modality-specific or invariant high-temporal dynamics. Electrocardiogram (EEG)
was recorded from healthy, normal subjects during beep-, flash- and click
counting tasks, which corresponded to auditory, visual and tactile modalities,
respectively. EEG dynamics regarding event-related spectral perturbations (ERSP)
in ICA time-series data were compared across the sensory modalities using a
multivariate pattern analysis. We found modality-specific EEG dynamics in the
prefrontal cortex, whereas we found modality-specific and cross-modal dynamics in
the early visual cortex.
PMID- 25130314
TI - Nursing grand rounds: a strategy for promoting evidence-based learning among
pediatric nurses.
AB - This paper describes the collaboration of nurses from five specialty units within
a large tertiary care pediatric hospital in the development and presentation of
Nursing Grand Rounds (NGR). NGR was generated, prepared, and presented quarterly
by bedside nurses to their peers in a professional format. NGR lasted 2hours,
were simultaneously offered via Webinar, and incorporated literature reviews,
guest/expert speakers, and case studies. In addition, attendees were eligible for
continuing education credits (CEUs). Based on favorable evaluations, NGR is
purported as a creative method for nurses to be kept up-to-date about evidence
and knowledge unique to their patient population.
PMID- 25130315
TI - Adipocyte transdifferentiation and its molecular targets.
AB - According to the World Health Organization obesity is defined as the excessive
accumulation of fat, which increases risk of other metabolic disorders such as
insulin resistance, dyslipidemia, hypertension, cardiovascular diseases, etc.
There are two types of adipose tissue, white and brown adipose tissue (BAT) and
the latter has recently gathered interest of the scientific community. Discovery
of BAT has opened avenues for a new therapeutic strategy for the treatment of
obesity and related metabolic syndrome. BAT utilizes accumulated fatty acids for
energy expenditure; hence it is seen as one of the possible alternates to the
current treatment. Moreover, browning of white adipocyte on exposure to cold, as
well as with some of the pharmacological agents presents exciting outcomes and
indicates the feasibility of transdifferentiation. A better understanding of
molecular pathways and differentiation factors, those that play a key role in
transdifferentiation are of extreme importance in designing novel strategies for
the treatment of obesity and associated metabolic disorders.
PMID- 25130317
TI - Commentary on "biochemical and immunomorphological evaluation of hepatocyte
growth factor and c-Met pathway in patients with critical limb ischemia":
regenerative therapy of chronically ischaemic wounds: land in sight?
PMID- 25130318
TI - Rafting through traffic: Membrane domains in cellular logistics.
AB - The intricate and tightly regulated organization of eukaryotic cells into
spatially and functionally distinct membrane-bound compartments is a defining
feature of complex organisms. These compartments are defined by their lipid and
protein compositions, with their limiting membrane as the functional interface to
the rest of the cell. Thus, proper segregation of membrane proteins and lipids is
necessary for the maintenance of organelle identity, and this segregation must be
maintained despite extensive, rapid membrane exchange between compartments.
Sorting processes of high efficiency and fidelity are required to avoid
potentially deleterious mis-targeting and maintain cellular function. Although
much molecular machinery associated with membrane traffic (i.e. membrane
budding/fusion/fission) has been characterized both structurally and
biochemically, the mechanistic details underlying the tightly regulated
distribution of membranes between subcellular locations remain to be elucidated.
This review presents evidence for the role of ordered lateral membrane domains
known as lipid rafts in both biosynthetic sorting in the late secretory pathway,
as well as endocytosis and recycling to/from the plasma membrane. Although such
evidence is extensive and the involvement of membrane domains in sorting is
definitive, specific mechanistic details for raft-dependent sorting processes
remain elusive.
PMID- 25130319
TI - Dual effect of thiol addition on fluorescent polymeric micelles: ON-to-OFF
emissive switch and morphology transition.
AB - The morphology transition from micelles to vesicles of a solution-state self
assembled block copolymer, containing a fluorescent dye at the core-shell
interface, has been induced by an addition-elimination reaction using a thiol,
and has been shown to be coupled to a simultaneous ON-to-OFF switch in particle
fluorescence.
PMID- 25130316
TI - Effects of soluble extracts from Leishmania infantum promastigotes, Toxoplasma
gondii tachyzoites on TGF-beta mediated pathways in activated CD4+ T lymphocytes.
AB - Interference with transforming growth factor-beta-mediated pathways helps several
parasites to survive for long periods in immunocompetent hosts. Macrophages and
dendritic cells infected by Toxoplasma, Leishmania and Plasmodium spp. produce
large amounts of transforming growth factor-beta and induce the differentiation
of antigen-specific T-regulatory cells. Mechanisms not mediated by antigen
presentation could also account for the expansion of T-regulatory cells in
parasitic diseases and they also might be mediated through transforming growth
factor-beta-receptor activated pathways. We explored the properties of soluble
extracts from Leishmania infantum promastigotes, Toxoplasma gondii tachyzoites,
Trichinella spiralis muscle larvae to expand the pool of T-regulatory cells in a
population of polyclonally activated T cells in the absence of accessory cells,
and compared their effects to those induced by Plasmodium falciparum extracts.
Similarly to P. falciparum, L. infantum extracts activate the latent soluble form
of transforming growth factor-beta and that bound to the membrane of activated T
lymphocytes. The interaction of the active cytokine with transforming growth
factor-beta receptor induces Foxp3 expression by activated lymphocytes, favoring
their conversion through the T-regulatory phenotype. Both Toxoplasma gondii and
L. infantum extracts are able to induce transforming growth factor-beta
production by activated T cells in the absence of accessory cells.
PMID- 25130320
TI - Survival of Atlantic salmon Salmo salar smolts through a hydropower complex.
AB - This study evaluated Atlantic salmon Salmo salar smolt survival through the lower
Penobscot River, Maine, U.S.A., and characterized relative differences in
proportional use and survival through the main-stem of the river and an
alternative migration route, the Stillwater Branch. The work was conducted prior
to removal of two main-stem dams and operational changes in hydropower facilities
in the Stillwater Branch. Survival and proportional use of migration routes in
the lower Penobscot were estimated from multistate (MS) models based on 6 years
of acoustic telemetry data from 1669 smolts and 2 years of radio-telemetry data
from 190 fish. A small proportion (0.12, 95% c.i. = 0.06-0.25) of smolts used the
Stillwater Branch, and mean survival through the two operational dams in this
part of the river was relatively high (1.00 and 0.97). Survival at Milford Dam,
the dam that will remain in the main-stem of the Penobscot River, was relatively
low (0.91), whereas survival through two dams that were removed was relatively
high (0.99 and 0.98). Smolt survival could decrease in the Stillwater Branch with
the addition of two new powerhouses while continuing to meet fish passage
standards. The effects of removing two dams in the main-stem are expected to be
negligible for smolt survival based on high survival observed from 2005 to 2012
at those locations. Survival through Milford Dam was been well below current
regulatory standards, and thus improvement of passage at this location offers the
best opportunity for improving overall smolt survival in the lower river.
PMID- 25130321
TI - Medical burden in bipolar disorder: findings from the Clinical and Health
Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study
(Bipolar CHOICE).
AB - OBJECTIVES: Individuals with bipolar disorder have high rates of other medical
comorbidity, which is associated with higher mortality rates and worse course of
illness. The present study examined common predictors of medical comorbidity.
METHODS: The Clinical and Health Outcomes Initiative in Comparative Effectiveness
for Bipolar Disorder study (Bipolar CHOICE) enrolled 482 participants with
bipolar I or bipolar II disorder in a six-month, randomized comparative
effectiveness trial. Baseline assessments included current and lifetime DSM-IV-TR
diagnoses, demographic information, psychiatric and medical history, severity of
psychiatric symptoms, level of functioning, and a fasting blood draw. Medical
comorbidities were categorized into two groups: cardiometabolic (e.g., diabetes,
hyperlipidemia, and metabolic syndrome) and non-cardiovascular (e.g., seizures,
asthma, and cancer). Additionally, we looked at comorbid substance use (e.g.,
smoking and drug dependence). RESULTS: We found that 96.3% of participants had at
least one other medical comorbidity. Older age predicted a greater likelihood of
having a cardiometabolic condition. Early age of onset of bipolar symptoms was
associated with a lower chance of having a cardiometabolic condition, but a
greater chance of having other types of medical comorbidity. Additional
predictors of other medical comorbidities in bipolar disorder included more time
spent depressed, less time spent manic/hypomanic, and longer duration of illness.
Medications associated with weight gain were associated with low high-density
lipoprotein and abnormal triglycerides. CONCLUSIONS: There appears to be a
substantial medical burden associated with bipolar disorder, highlighting the
need for collaborative care among psychiatric and general medical providers to
address both psychiatric and other medical needs concomitantly in this group of
patients.
PMID- 25130322
TI - Shape-shift: semicircular canal morphology responds to selective breeding for
increased locomotor activity.
AB - Variation in semicircular canal morphology correlates with locomotor agility
among species of mammals. An experimental evolutionary mouse model was used to
test the hypotheses that semicircular canal morphology (1) evolves in response to
selective breeding for increased locomotor activity, (2) exhibits phenotypic
plasticity in response to early-onset chronic exercise, and (3) is unique in
individuals possessing the minimuscle phenotype. We examined responses in canal
morphology to prolonged wheel access and selection in laboratory mice from four
replicate lines bred for high voluntary wheel-running (HR) and four nonselected
control (C) lines. Linear measurements and a suite of 3D landmarks were obtained
from 3D reconstructions of MUCT-scanned mouse crania (MUCT is microcomputed
tomography). Body mass was smaller in HR than C mice and was a significant
predictor of both radius of curvature and 3D canal shape. Controlling for body
mass, radius of curvature did not differ statistically between HR and C mice, but
semicircular canal shape did. Neither chronic wheel access nor minimuscle
affected radius of curvature or canal shape These findings suggest that
semicircular canal morphology is responsive to evolutionary changes in locomotor
behavior, but the pattern of response is potentially different in small- versus
large-bodied species.
PMID- 25130323
TI - Barriers to evidence-based medicine: a systematic review.
AB - INTRODUCTION: Evidence-based medicine (EBM) has emerged as an effective strategy
to improve health care quality. The aim of this study was to systematically
review and carry out an analysis on the barriers to EBM. METHODS: Different
database searching methods and also manual search were employed in this study
using the search words ('evidence-based' or 'evidence-based medicine' or
'evidence-based practice' or 'evidence-based guidelines' or 'research
utilization') and (barrier* or challenge or hinder) in the following databases:
PubMed, Scopus, Web of Knowledge, Cochrane library, Pro Quest, Magiran, SID.
RESULTS: Out of 2592 articles, 106 articles were finally identified for study.
Research barriers, lack of resources, lack of time, inadequate skills, and
inadequate access, lack of knowledge and financial barriers were found to be the
most common barriers to EBM. Examples of these barriers were found in primary
care, hospital/specialist care, rehabilitation care, medical education,
management and decision making. The most common barriers to research utilization
were research barriers, cooperation barriers and changing barriers. Lack of
resources was the most common barrier to implementation of guidelines.
CONCLUSION: The result of this study shows that there are many barriers to the
implementation and use of EBM. Identifying barriers is just the first step to
removing barriers to the use of EBM. Extra resources will be needed if these
barriers are to be tackled.
PMID- 25130324
TI - A genome-wide search for quantitative trait loci affecting the cortical surface
area and thickness of Heschl's gyrus.
AB - Heschl's gyrus (HG) is a core region of the auditory cortex whose morphology is
highly variable across individuals. This variability has been linked to sound
perception ability in both speech and music domains. Previous studies show that
variations in morphological features of HG, such as cortical surface area and
thickness, are heritable. To identify genetic variants that affect HG morphology,
we conducted a genome-wide association scan (GWAS) meta-analysis in 3054 healthy
individuals using HG surface area and thickness as quantitative traits. None of
the single nucleotide polymorphisms (SNPs) showed association P values that would
survive correction for multiple testing over the genome. The most significant
association was found between right HG area and SNP rs72932726 close to gene
DCBLD2 (3q12.1; P=2.77 * 10(-7) ). This SNP was also associated with other
regions involved in speech processing. The SNP rs333332 within gene KALRN
(3q21.2; P=2.27 * 10(-6) ) and rs143000161 near gene COBLL1 (2q24.3; P=2.40 * 10(
6) ) were associated with the area and thickness of left HG, respectively. Both
genes are involved in the development of the nervous system. The SNP rs7062395
close to the X-linked deafness gene POU3F4 was associated with right HG thickness
(Xq21.1; P=2.38 * 10(-6) ). This is the first molecular genetic analysis of
variability in HG morphology.
PMID- 25130325
TI - Systematic review: internet-based program for youth smoking prevention and
cessation.
AB - PURPOSE: To review the characteristics and effects Internet-based youth smoking
prevention and cessation programs. DESIGN: Systematic review of published
articles in peer-reviewed journals in the past 10 years, focused on Internet
based youth smoking prevention and cessation programs. METHODS: Twelve articles
were selected based on the following criteria: studies reporting the outcomes of
Internet-based smoking cessation or prevention intervention programs for
adolescents who are younger than 24 years. FINDINGS: The components of youth
Internet-based smoking intervention programs are analyzed based on study features
(i.e., sample, design, theoretical basis, analysis, outcome measures) and program
characteristics (i.e., focus, setting, frequency, duration, intensity, and
different components) that make the programs effective. The most common
components of effective Internet-based programs are identified as the following:
the use of multimedia, tailored approaches, personalized feedback, and
interactive features. CONCLUSIONS: The characteristics and effects of the
programs vary, but most programs show positive results in youth smoking
prevention and cessation in spite of the studies' limitations. CLINICAL
RELEVANCE: The evidence from this review provides useful information of recent
efforts related to Internet-based youth smoking prevention and cessation
programs, which can have significant clinical implications in developing future
innovative youth smoking prevention and intervention programs.
PMID- 25130326
TI - Graft rejection and failure following endothelial keratoplasty (DSAEK) and
penetrating keratoplasty for secondary endothelial failure.
AB - PURPOSE: To compare the frequency of rejection and graft failure after Descemet's
stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty
(PK) for secondary endothelial failure. METHODS: Seventy-eight eyes undergoing
DSAEK from 2006 to 2013 and 80 eyes undergoing PK from 1998 to 2013 were
included. Indications were endothelial failure due to pseudophakic bullous
keratopathy (82%), previous eye trauma (8%), uveitis (4%) or other causes (6%).
Rejection episodes and graft failure were recorded, together with preoperative
risk factors (glaucoma, neovascularization and active inflammation). Kaplan-Meier
survival curves with up to 4 years follow-up were used to compare DSAEK with PK,
as well as low-risk with high-risk eyes. RESULTS: During follow-up, 15% of the PK
treated eyes and 4% of the DSAEK-treated eyes experienced rejection. Graft
failure occurred in 8% of the PK-treated eyes and in 7% of the DSAEK-treated
eyes. No significant differences were found in the rate of rejection (p=0.11),
graft failure (p=0.29) or rejection-related graft failure (p=0.30) between DSAEK
and PK in low-risk eyes. In DSAEK, high-risk eyes (mainly with glaucoma)
experienced significantly more rejection episodes (p=0.01), graft failures
(p=0.04) and rejection-related graft failures (p=0.04) compared with low-risk
eyes. No differences were seen between high-risk and low-risk PK-treated eyes
(p>0.40). CONCLUSION: In the present, relatively small study, no differences in
rejection rate or graft failure were found between DSAEK and PK in low-risk eyes.
However, glaucoma seems to increase the risk of graft complications after DSAEK
for secondary endothelial failure. Long-term studies of larger samples sizes are
needed to confirm this.
PMID- 25130327
TI - Can platelet count and mean platelet volume during the first trimester of
pregnancy predict preterm premature rupture of membranes?
AB - AIM: The aim of our study was to evaluate the values of platelet count and mean
platelet volume (MPV) obtained from maternal serum during the first trimester to
predict subsequent preterm premature rupture of membranes (PPROM). MATERIAL AND
METHODS: The records of 318 women with PPROM and 384 healthy controls in a single
center between 2009 and 2013 were retrospectively evaluated. Platelet count and
MPV values between 7 and 14 weeks of gestation were compared. Receiver-operator
curve analysis was performed to identify the optimal platelet count and MPV cut
off levels predicting PPROM. RESULTS: Compared with controls, women with PPROM
had significantly increased levels of platelet count and significantly decreased
levels of MPV in the first trimester (P < 0.001). The area under the receiver
operator curve was 0.642 for MPV and 0.579 for platelet count. The cut-off values
of MPV <= 8.6 fL and platelet count >=216 * 10(3) /MUL predicted PPROM with a
sensitivity of 58% and 65% and specificity of 62% and 44%, respectively.
CONCLUSION: MPV can be used as a more efficient predictor for an early diagnosis
of PPROM than platelet count. However, further research combining other markers
is needed to increase the efficiency of prediction.
PMID- 25130329
TI - NIR photoregulated chemo- and photodynamic cancer therapy based on conjugated
polyelectrolyte-drug conjugate encapsulated upconversion nanoparticles.
AB - The design of nanoplatforms with target recognition and near-infrared (NIR) laser
photoregulated chemo- and photodynamic therapy is highly desirable but remains
challenging. In this work, we have developed such a system by taking advantage of
a conjugated polyelectrolyte (CPE)-drug conjugate and upconversion nanoparticles
(UCNPs). The poly(ethylene glycol) (PEG) grafted CPE not only serves as a polymer
matrix for UCNP encapsulation, but also as a fluorescent imaging agent, a
photosensitizer as well as a carrier for chemotherapeutic drug doxorubicin (DOX)
through a UV-cleavable ortho-nitrobenzyl (NB) linker. Upon 980 nm laser
irradiation, the UCNPs emit UV and visible light. The up-converted UV light is
utilized for controlled drug release through the photocleavage of the ortho
nitrobenzyl linker, while the up-converted visible light is used to initiate the
polymer photosensitizer to produce reactive oxygen species (ROS) for photodynamic
therapy. The NIR photo-regulated UCNP@CPE-DOX showed high efficiency of ROS
generation and controlled drug release in cancer cells upon single laser
irradiation. In addition, the combination therapy showed enhanced inhibition of
U87-MG cell growth as compared to sole treatments. As two light sources with
different wavelengths are always needed for traditional photodynamic therapy and
photoregulated drug release, the adoption of UCNPs as an NIR light switch is
highly beneficial to combined chemo- and photodynamic therapy with enhanced
therapeutic effects.
PMID- 25130328
TI - Interferon regulatory factor 3 as key element of the interferon signature in
plasmacytoid dendritic cells from systemic lupus erythematosus patients: novel
genetic associations in the Mexican mestizo population.
AB - Many genetic studies have found an association between interferon regulatory
factors (IRF) single nucleotide polymorphisms (SNPs) and systemic lupus
erythematosus (SLE); however, specific dendritic cell (DC) alterations have not
been assessed. The aim of the present study was to address the expression of IRF3
and IRF5 on different DC subsets from SLE patients, as well as their association
with interferon (IFN)-alpha production and novel SNPs. For the genetic
association analyses, 156 SLE patients and 272 healthy controls from the Mexican
mestizo population were included. From these, 36 patients and 36 controls were
included for functional analysis. Two IRF3 SNPs - rs2304206 and rs2304204 - were
determined. We found an increased percentage of circulating pDC in SLE patients
in comparison to controls (8.04 +/- 1.48 versus 3.35 +/- 0.8, P = 0.032). We also
observed enhanced expression of IRF3 (64 +/- 6.36 versus 36.1 +/- 5.57, P =
0.004) and IRF5 (40 +/- 5.25 versus 22.5 +/- 2.6%, P = 0.010) restricted to this
circulating pDC subset from SLE patients versus healthy controls. This finding
was associated with higher IFN-alpha serum levels in SLE (160.2 +/- 21 versus
106.1 +/- 14 pg/ml, P = 0.036). Moreover, the IRF3 rs2304206 polymorphism was
associated with increased susceptibility to SLE [odds ratio (OR), 95% confidence
interval (CI) = 2.401 (1.187-4.858), P = 0.021] as well as enhanced levels of
serum type I IFN in SLE patients who were positive for dsDNA autoantibodies. The
IRF3 rs2304204 GG and AG genotypes conferred decreased risk for SLE. Our findings
suggest that the predominant IRF3 expression on circulating pDC is a key element
for the increased IFN-alpha activation based on the interplay between the
rs2304206 gene variant and the presence of dsDNA autoantibodies in Mexican
mestizo SLE patients.
PMID- 25130330
TI - Cryopreserved platelets: frozen in a logjam?
PMID- 25130331
TI - Chikungunya virus: new risk to transfusion safety in the Americas.
PMID- 25130332
TI - Transfusion medicine illustrated. An allergic transfusion reaction with
angioedema.
PMID- 25130333
TI - Apples, oranges, and autotransfusion techniques.
PMID- 25130334
TI - In reply.
PMID- 25130336
TI - Coagulation values in extreme premature infants.
PMID- 25130335
TI - Safety measures to prevent hepatitis E virus transmission by blood transfusion.
PMID- 25130337
TI - Obesity.
AB - This narrative symposium was inspired by the American Medical Associations (AMA)
decision to label obesity a disease. How do people who have been classified as
obese feel this decision impacts on their lives? Personal narrative authors offer
their experiences with obesity and healthcare. The symposium also hosts five
commentary articles from scholars and stakeholders with a wide range of
perspectives. These articles pull from themes in the personal narratives and
bring them into dialogue with the current scholarly literature on this topic.
PMID- 25130338
TI - I am not obese. I am just fat.
PMID- 25130339
TI - Experiences of an obese patient.
PMID- 25130340
TI - Shame is not an effective diet plan.
PMID- 25130341
TI - Little body hidden within.
PMID- 25130342
TI - My story: evolving obesities.
PMID- 25130343
TI - Explode and die! A fat woman's perspective on prenatal care and the fat panic
epidemic.
PMID- 25130344
TI - Fitness, fatness, and aesthetic judgments of the female body: what the AMA
decision to medicalize obesity means for other non-normal female bodies.
PMID- 25130345
TI - Obesity treatment: one size does not fit all.
PMID- 25130346
TI - Stepping off the edge of the earth: a bariatric patient's journey out of obesity.
PMID- 25130347
TI - I'm Your Patient, Not a Problem.
PMID- 25130348
TI - Journey to wellness.
PMID- 25130349
TI - Obesity as disease: definition by desperation.
PMID- 25130350
TI - Fatness, medicalization, and stigma: on the need to do better.
AB - This article comments on a collection of remarkable narratives authored by fat
writers addressing the American Medical Association's decision to label obesity a
disease. Endeavoring to avoid what has been termed "thinsplaining," the
commentary examines the voices of the writers in the hopes of identifying key
themes and points that emerge from these fat narratives. The commentary canvasses
the writers' perspectives on topics such as the medicalization and
pathologization of fat, the Western and especially American tendency to emphasize
individual culpability for fatness, and, of course, the horrific commonality and
intensity of fat stigma. Stigma is a particular focus for the commentary, both
because it is a principal theme in the collection, and also because it is
important to understand precisely what stigma is and its deep connections to
larger macrosocial structures. The commentary concludes with a simple admonition,
gleaned from the narratives: we should strive to do better.
PMID- 25130351
TI - When one size does not fit all: a commentary.
AB - This commentary explores a few of the common threads in a symposium of obesity
narratives in light of the American Medical Association's classification of
obesity as a disease. While the narratives illustrate the breadth of experiences,
they each highlight the absence of a clear approach for the treatment of obesity,
as well as the lack of conversation and compassion in the most basic of
interactions with medical professionals. This could be cause for despair, yet we
learn through these shared experiences that we can take control of our care and
plot a course for real and lasting assistance with this condition.
PMID- 25130352
TI - The burden of obesity: personal stories, professional insights.
AB - The word obesity invokes multiple connotations that contain a realm of disparate
descriptions ranging from disease to disdain. There are also few other human
conditions that cause increased morbidity and mortality and affect millions of
individuals worldwide yet is still viewed by many as a character fault or moral
failure. Herein we have the opportunity to read the personal reflections of
individuals with obesity who have struggled with their weight over a lifetime.
Through a series of 12 narratives, the authors collectively share their shame,
humiliation, dignity, inner strength and advice for health professionals who they
entrust.
PMID- 25130353
TI - Die another day: the obstacles facing fat people in accessing quality healthcare.
AB - In this issue of Narrative Inquiries in Bioethics, fat individuals share their
healthcare experiences. Through reading the narratives, it becomes clear that
access to proper healthcare is often blocked for fat patients by a variety of
things, including shame and fat stigma. From physical spaces in which they do not
fit, to doctors who diagnose all of their problems as 'fat', similar themes are
echoed across the stories. And common are the refrains for better treatment, less
shame, and access to evidenced based care from educated providers. In this
manuscript, I highlight common themes from the stories and integrate them with
themes from the literature. I allow the two dissenting narratives to suggest
other ways of thinking about fatness and well-being. And I conclude by suggesting
ways to provide better access to quality healthcare for fat individuals.
PMID- 25130354
TI - Risk factor medicalization, hubris, and the obesity disease.
AB - The essays on obesity in this issue frequently refer to the recent American
Medical Association (AMA) declaration of obesity as a disease. In response to
these essays, I describe and explore the significance of 'risk-factor
medicalization' and how negative unintended consequences with this approach to
disease modeling are exemplified in many of the essays. I also relate the essays'
content to the issue of physician hubris in the face of their own helplessness in
aiding the obese patient.
PMID- 25130355
TI - Stories worth telling: moral experiences of suicidal behavior.
AB - Moral constructions of suicide are deliberately avoided in contemporary
suicidology, yet morality persists, little or imperfectly acknowledged, in its
practices and in the policies, discourses, and instruments that it underpins.
This study used narrative methodologies to examine the normative force of
suicidology and its implications for persons who had engaged in an act of
nonfatal suicidal behavior. I interviewed a convenience sample of twelve persons
from two inner-urban community mental health centers who were receiving crisis
and case management services after a recent act of nonfatal suicidal behavior.
Interviews focused on events leading up to and after participants' suicidal
behavior; the responses their suicidal behavior generated in others, including
family, friends, and the health professionals caring for them; and cultural views
of suicide more broadly. Analysis of these interviews revealed that, although
participants' narratives were broadly consistent with a number of recognizable,
canonical story formats common to our cultural repertoire of stories of suicide,
they also revealed important tensions, divisions, conflicts, and challenges to
contemporary suicidological discourse and practice. Despite evidence to suggest
that biomedical understandings of suicide provided some therapeutic benefit to
participants, they did not address important social and moral dimensions of human
life or explore their connection to suicidal behavior-aspects of the suicidal
event that were critical to its causation and to its retelling and "resolution."
The results of this study provide important insights into the moral features of
suicidal behavior, the moral and ethical implications of suicide research, and
the limitations of moral and ethical discourse in suicidology.
PMID- 25130356
TI - Desperately seeking a surrogate - for a patient lacking decision-making capacity.
AB - Our hospital's policy and procedures for "Patients Without Surrogates" provides
for gradated safeguards for managing patients' treatment and care when they lack
decision-making capacity, have no advance directives, and no surrogate decision
makers are available. The safeguards increase as clinical decisions become more
significant and have greater consequences for the patient. The policy also
directs social workers to engage in "rigorous efforts" to search for surrogates
who can potentially provide substituted judgments for such patients. We describe
and illustrate the policy, procedures, and kinds of expected rigorous efforts
through our narration of an actual but disguised case for which we provided
clinical ethics guidance and social work expertise. Our experience with and
reflection on this case resulted in four recommendations we make for health care
facilities and organizations that aim to provide quality care for their own
patients without surrogates.
PMID- 25130357
TI - Dax's case redux: when comes the end of the day?
AB - Forty years after Dax Cowart fought to have his voice heard regarding his medical
treatment, patient autonomy and rights are at the heart of patient care today.
Yet, despite its centrality in patient care, the tension between a severely
burned patient's right to stop treatment and the physician's role in saving a
life has not abated. As this case study explores, barriers remain to hearing and
respecting a patient's treatment decisions. Dismantling these barriers involves
dispelling the myths that burn patients must grin and bear intense pain to
recover and that a patient's choice to discontinue treatment equals physician
failure. Moreover, in these situations, sustained, direct engagement between
physician and patient can reduce the moral distress of all involved and enable
physicians to hear and better accept when a patient is calling for the end of the
day.
PMID- 25130358
TI - Undocumented and at the end of life.
AB - Three of the most contentious issues in contemporary American society-allocation
of medical resources, end of life care, and immigration-converge when
undocumented immigrant patients are facing the terminal phase of chronic illness.
The lack of consistent, pragmatic policy in each of these spheres leaves us with
little guidance for how to advocate for undocumented patients at the end of life.
Limited resources and growing need compound the problem. Care for patients in
this unfortunate situation should be grounded in clinical and economic reality as
well as respect for the dignity of the individual to avoid exacerbating
inequalities.
PMID- 25130359
TI - Calling obesity a disease is a terrible decision.
PMID- 25130360
TI - The weight I just can't lose.
PMID- 25130361
TI - You mean it's not my fault: learning about lipedema, a fat disorder.
PMID- 25130362
TI - Editors' note.
PMID- 25130363
TI - The ZnSn(OH)6 nanocube-graphene composite as an anode material for Li-ion
batteries.
AB - ZnSn(OH)6 (ZSH) nanocubes with a uniform size of 40-80 nm were synthesized by
using a simple hydrothermal route and then combined with graphene sheets (rGO)
via the electrostatic interaction. The formed composite of ZnSn(OH)6 nanocube
graphene (ZSH-rGO) was used as an anode material for Li-ion batteries and it
exhibited significantly enhanced electrochemical performance. For instance, a
capacity of 540 mA h g(-1) at 500 mA g(-1) was retained after 40 cycles.
PMID- 25130364
TI - A comparison of four gutta-percha filling techniques in simulated C-shaped
canals.
AB - AIM: To compare four gutta-percha filling techniques in simulated C-shaped canals
based on filling quality at three cross-sectional levels, filling time and the
apical extrusion of gutta-percha. METHODOLOGY: Forty resin simulated C-shaped
canals were constructed and filled using one of four techniques: cold lateral
compaction (LC), ultrasonic compaction (UC), single cone with injectable gutta
percha (Obtura II(TM) ) (IT) and core-carrier (Thermafil((r)) ) (CC). Cross
sections were made at 1 (L1), 3 (L3) and 6 (L6) mm from the canal terminus. Areas
of gutta-percha, sealer and voids in each cross section were measured using an
image analysis system. Data were analysed using a univariate general linear model
and post hoc test (Dunnett's T3). Data on time taken to fill canals was evaluated
using the Bonferroni post hoc test. RESULTS: CC had more gutta-percha and less
sealer compared with IT at L1 (P < 0.05). LC had marginally significantly less
gutta-percha than CC at this level (P = 0.049). At level 3 mm, significantly more
gutta-percha and less sealer were present in IT compared with LC (P < 0.05). The
techniques showed no difference in quality at L6. The time for LC (20.72 min) was
three times longer than for both IT (6.11 min) and CC (6.67 min), whereas for UC
(26.92 min), it was four times longer (P < 0.001). Finally, the four techniques
were not different in the occurrence of apical extrusion of gutta-percha.
CONCLUSIONS: The core-carrier technique was the most effective technique when
assessed by gutta-percha area in this simulated C-shaped canal.
PMID- 25130365
TI - M2(m-dobdc) (M = Mg, Mn, Fe, Co, Ni) metal-organic frameworks exhibiting
increased charge density and enhanced H2 binding at the open metal sites.
AB - The well-known frameworks of the type M2(dobdc) (dobdc(4-) = 2,5-dioxido-1,4
benzenedicarboxylate) have numerous potential applications in gas storage and
separations, owing to their exceptionally high concentration of coordinatively
unsaturated metal surface sites, which can interact strongly with small gas
molecules such as H2. Employing a related meta-functionalized linker that is
readily obtained from resorcinol, we now report a family of structural isomers of
this framework, M2(m-dobdc) (M = Mg, Mn, Fe, Co, Ni; m-dobdc(4-) = 4,6-dioxido
1,3-benzenedicarboxylate), featuring exposed M(2+) cation sites with a higher
apparent charge density. The regioisomeric linker alters the symmetry of the
ligand field at the metal sites, leading to increases of 0.4-1.5 kJ/mol in the H2
binding enthalpies relative to M2(dobdc). A variety of techniques, including
powder X-ray and neutron diffraction, inelastic neutron scattering, infrared
spectroscopy, and first-principles electronic structure calculations, are applied
in elucidating how these subtle structural and electronic differences give rise
to such increases. Importantly, similar enhancements can be anticipated for the
gas storage and separation properties of this new family of robust and
potentially inexpensive metal-organic frameworks.
PMID- 25130367
TI - Edge effects in the primate community of the biological dynamics of Forest
Fragments Project, Amazonas, Brazil.
AB - While much is known about abiotic and vegetative edge effects in tropical
forests, considerably less is known about the impact of forest edges on large
mammals. In this study, we examine edge effects in a primate community to
determine: 1) the distance from the edge over which edge effects in primate
density are detectable, 2) whether individual species exhibit edge effects in
their density, and 3) whether biological characteristics can be used to predict
primate presence in edge habitats. Given their importance to many primate
species, we also examine the influence of the number of large trees. We found
edge penetration distances of 150 m for the five species that experienced edge
effects, suggesting that primates respond to edge-related changes in the plant
community that are known to be strongest over the first 150 m. Four species had
higher edge densities: Alouatta macconnelli (folivore-frugivore), Chiropotes
chiropotes (frugivorous seed predator), Saguinus midas (frugivore-faunivore), and
Sapajus apella apella (frugivore-faunivore); one species' density was lower:
Ateles paniscus (frugivore); and the final species, Pithecia chrysocephala
(frugivorous seed predator), did not show an edge-related pattern. The lone
significant relationship between the biological characteristics examined (body
weight, diet, group size, and home range size) and primate presence in edge
habitats was a negative relationship with the amount of fruit consumed. Though we
did not examine primate responses to edges that border a denuded matrix, we have
shown that edges influence primate distribution even following decades of
secondary forest regeneration at habitat edges.
PMID- 25130366
TI - Quantitative super-resolution imaging of Bruchpilot distinguishes active zone
states.
AB - The precise molecular architecture of synaptic active zones (AZs) gives rise to
different structural and functional AZ states that fundamentally shape chemical
neurotransmission. However, elucidating the nanoscopic protein arrangement at AZs
is impeded by the diffraction-limited resolution of conventional light
microscopy. Here we introduce new approaches to quantify endogenous protein
organization at single-molecule resolution in situ with super-resolution imaging
by direct stochastic optical reconstruction microscopy (dSTORM). Focusing on the
Drosophila neuromuscular junction (NMJ), we find that the AZ cytomatrix (CAZ) is
composed of units containing ~137 Bruchpilot (Brp) proteins, three quarters of
which are organized into about 15 heptameric clusters. We test for a quantitative
relationship between CAZ ultrastructure and neurotransmitter release properties
by engaging Drosophila mutants and electrophysiology. Our results indicate that
the precise nanoscopic organization of Brp distinguishes different physiological
AZ states and link functional diversification to a heretofore unrecognized
neuronal gradient of the CAZ ultrastructure.
PMID- 25130369
TI - Decline in self-reported health (EQ-5D) over time after surgical reconstruction
of the right ventricular outflow tract: a longitudinal cohort study of 103
patients.
AB - OBJECTIVE: Patients with congenital heart disease may be operated with surgical
reconstruction of the right ventricular outflow tract (RVOT). Reintervention is
common in this group of patients. The aim of this study was to examine
longitudinal self-reported health measured by the EQ-5D questionnaire. DESIGN:
Data were collected from the Swedish Registry of Congenital Heart Disease. EQ-5D,
which measures health outcome, was introduced into the registry in 2005. All
adult patients with previous surgical reconstruction of the RVOT who had EQ-5D
data from their first and latest visit were analyzed. RESULTS: Among 103 patients
(65 male and 38 female), mean age 31 (range 19-78 years), the diagnoses were:
tetralogy of Fallot (n = 66); truncus, transpositions, and double outlet right
ventricle (n = 23); and Ross-operated congenital aortic valve disease (n = 14).
Time from first to latest visit was 3 years (range 1-7 years). Eighteen patients
underwent 26 reinterventions in the observational period from the first to latest
visit, including operations, percutaneous interventions, pacemaker implantations,
and ablations. Health perception, mean EQ-5D visual analog scale, VAS, declined
from 84.4 (standard deviation (SD) = 14.6) to 78.6 (SD = 18.3) at the latest
visit, P = .001. The decline is almost exclusively seen in patients without
reinterventions. Low EQ-VAS was associated with symptoms and New York Heart
Association class II-IV. Patient-reported problems in the EQ-5D dimension usual
activities were more common in the patients having reinterventions (25%) than
those without reintervention (7%), P = .04. CONCLUSION: In this longitudinal
cohort study of patients with previous surgical reconstruction of the RVOT,
health perception declined over time. The decline was not observed in patients
undergoing any additional interventions.
PMID- 25130368
TI - Examining gender difference in adult-onset psychosis in Hong Kong.
AB - AIM: Gender-specific treatment strategies for psychosis have been suggested in
recent years. Data on gender difference were largely consistent regarding
premorbid functioning, age of onset and negative symptoms; however, results
regarding neurocognitive function and duration of untreated psychosis were mixed
and inconclusive. In this study, we aimed at a thorough examination on the gender
differences in 360 Chinese patients with first-episode psychosis in Hong Kong.
METHODS: From June 2009 to August 2011, participants were consecutively recruited
from a population-based territory-wide study of early psychosis targeting first
episode psychosis in Hong Kong. Comprehensive data on basic demographics,
premorbid functioning and schizoid and schizotypal traits, clinical, functioning,
medication side effects and a battery of neurocognitive measures were collected
upon entry into the service. RESULTS: In 360 patients with first-episode
psychosis aged between 26 and 55 years, 43.6% (n = 157) were male and 56.4% (n =
203) were female. Males had poorer premorbid functioning and adjustment, earlier
age of onset, more negative symptoms and poorer functioning in terms of work
productivity, independent living and immediate social network relationships at
presentation of first-episode psychosis. Interestingly, our data indicate that
males tend to be more educated, and also characterized by higher IQ, better
neurocognitive performance on visual domain compared with females. Duration of
untreated psychosis was not different between the two genders. CONCLUSION: Data
from this homogeneous cohort of Chinese populations enabled tailored and
culturally sensitive recommendation on gender-specific treatment strategies,
hence improving patients' care and facilitate better diagnostic and
interventional decisions for patients with psychosis.
PMID- 25130370
TI - Validation of a field based chromatin dispersion assay to assess sperm DNA
fragmentation in the bottlenose dolphin (Tursiops truncatus).
AB - Over the last two decades, there have been significant advances in the use of
assisted reproductive technology for genetic and reproductive management of
captive dolphin populations, including evaluation of sperm DNA quality. This
study validated a customized sperm chromatin dispersion test (SCDt) for the
bottlenose dolphin (Tursiops truncatus) as a means of assessing sperm DNA damage
both in the field and in the laboratory. After performing the SCDt, two different
sperm morphotypes were identified: (i) sperm with fragmented DNA showed large
haloes of dispersed DNA fragments emerging from a compact sperm nucleoid core and
(ii) sperm containing non-fragmented DNA displayed small compact haloes
surrounded by a dense core of non-dispersed DNA and protein complex. Estimates of
sperm DNA fragmentation by means of SCDt were directly comparable to results
obtained following a two-tailed comet assay and showed a significant degree of
correlation (r = 0.961; p < 0.001). This investigation also revealed that the
SCDt, with minor modifications to the standard protocol, can be successfully
conducted in the field using a LED florescence microscopy obtaining a high
correlation (r = 0.993; p = 0.01) between the data obtained in the laboratory and
in the field.
PMID- 25130372
TI - Extracellular DNA traps in bronchoalveolar fluid from a murine eosinophilic
pulmonary response.
AB - Asthma is associated with a loss of the structural integrity of airway epithelium
and dysfunction of the physical barrier, which protects airways from external
harmful factors. Granulocyte activation causes the formation of extracellular
traps, releasing web-like structures of DNA and proteins, being important to kill
pathogens extracellularly. We investigated whether eosinophils infiltrating
airways in an experimental model of asthma would induce eosinophil extracellular
traps (EETs) in bronchoalveolar lavage fluid and lung tissue. We showed that an
ovalbumin (OVA) asthma protocol presented a significant increase in eosinophil
counts with increased extracellular DNA in bronchoalveolar lavage fluid as well
as in lung tissue, confirming the presence of DNA traps colocalized with
eosinophil peroxidase. EETs formation was reversed by DNase treatment. With these
approaches, we demonstrated for the first time that OVA-challenged mice release
extracellular DNA traps, which could aggravate pulmonary dysfunction.
PMID- 25130371
TI - miR-338-3p is over-expressed in blood, CFS, serum and spinal cord from sporadic
amyotrophic lateral sclerosis patients.
AB - Amyotrophic lateral sclerosis (ALS) is a progressive and seriously disabling
adult-onset neurological disease. Ninety percent of ALS patients are sporadic
cases (sALS) with no clear genetic linkage. Accumulating evidence indicates that
various microRNAs (miRNAs), expressed in a spatially and temporally controlled
manner in the brain, play a key role in neuronal development. In addition,
microRNA dysregulation contributes to some mental disorders and neurodegeneration
diseases. In our research, the expression of one selected miRNA, miR-338-3p,
which previously we have found over-expressed in blood leukocytes, was studied in
several different tissues from sALS patients. For the first time, we detected a
specific microRNA disease-related upregulation, miR-338-3p, in blood leukocytes
as well in cerebrospinal fluid, serum, and spinal cord from sALS patients.
Besides, staining of in situ hybridization showed that the signals of miR-338-3p
were localized in the grey matter of spinal cord tissues from sALS autopsied
patients. We propose that miRNA profiles found in tissue samples from sALS
patients can be relevant to understand sALS pathogenesis and lead to set up
effective biomarkers for sALS early diagnosis.
PMID- 25130373
TI - Resource loss, self-efficacy, and family support predict posttraumatic stress
symptoms: a 3-year study of earthquake survivors.
AB - BACKGROUND AND OBJECTIVES: Social support and self-efficacy are regarded as
coping resources that may facilitate readjustment after traumatic events. The
2009 Cinchona earthquake in Costa Rica serves as an example for such an event to
study resources to prevent subsequent severity of posttraumatic stress symptoms.
DESIGN: At Time 1 (1-6 months after the earthquake in 2009), N=200 survivors were
interviewed, assessing resource loss, received family support, and posttraumatic
stress response. At Time 2 in 2012, severity of posttraumatic stress symptoms and
general self-efficacy beliefs were assessed. METHODS: Regression analyses
estimated the severity of posttraumatic stress symptoms accounted for by all
variables. Moderator and mediator models were examined to understand the
interplay of received family support and self-efficacy with posttraumatic stress
symptoms. RESULTS: Baseline posttraumatic stress symptoms and resource loss (T1)
accounted for significant but small amounts of the variance in the severity of
posttraumatic stress symptoms (T2). The main effects of self-efficacy (T2) and
social support (T1) were negligible, but social support buffered resource loss,
indicating that only less supported survivors were affected by resource loss.
Self-efficacy at T2 moderated the support-stress relationship, indicating that
low levels of self-efficacy could be compensated by higher levels of family
support. Receiving family support at T1 enabled survivors to feel self
efficacious, underlining the enabling hypothesis. CONCLUSIONS: Receiving social
support from relatives shortly after an earthquake was found to be an important
coping resource, as it alleviated the association between resource loss and the
severity of posttraumatic stress response, compensated for deficits of self
efficacy, and enabled self-efficacy, which was in turn associated with more
adaptive adjustment 3 years after the earthquake.
PMID- 25130375
TI - A quantitative evaluation method using processed optical images and analysis of
age-dependent changes on nasolabial lines.
AB - BACKGROUND/PURPOSE: Nasolabial lines (NL) and wrinkles of the face are major
features of aging. Wrinkles have been studied widely by morphological methods
using 3-dimensional (3D) photographic analysis instrument, but NL were evaluated
by visual scoring usually. To evaluate NL quantitatively, another method is
needed. This study is purposed to find out quantitative method for evaluation of
NL. METHOD: One hundred Korean female subjects aged 20 to 60 were recruited in
this study. Facial image was taken using light source adjusted VISIA-CR((r)) and
3-dimensional wrinkle depth on the NL area was evaluated by Phase shift rapid in
vivo measuring of human skin (PRIMOS((r))). The pixel number of NL area and the
angle were obtained using processed images. The severity of NL was assessed by
visual score. Skin elasticity was measured by Cutometer((r)) MPA580. Statistical
significance was determined at P < 0.05. RESULT: The optical images obtained by
light source adjusted VISIA-CR((r)) were easy to distinguish NL and significantly
increased age-dependently. And three parameters of elasticity (R2, R5, and R7) on
NL area were gradually decreased with age. The Pearson correlation coefficient
was -0.756 (P < 0.01) between R7 parameter and ages. Also the pixel number of NL
area, angle, wrinkle depth on the NL area (Ra), and visual score were decreased
elasticity-dependently. The pixel number of NL area was highly related to Ra (r =
0.567, P < 0.01) and visual score (r = 0.647, P < 0.01). CONCLUSION: This study
has shown that NL severity is related to decrease of dermal elasticity and age
using quantitative new method by processing optical images.
PMID- 25130376
TI - TGFbeta1 increases microglia-mediated engulfment of apoptotic cells via
upregulation of the milk fat globule-EGF factor 8.
AB - Milk fat globule-epidermal growth factor-factor 8 (Mfge8) has been described as
an essential molecule during microglia-mediated clearance of apoptotic cells via
binding to phosphatidylserine residues and subsequent phagocytosis. Impaired
uptake of apoptotic cells by microglia results in prolonged inflammatory
responses and damage of healthy cells. Although the mechanisms of Mfge8-mediated
engulfment of apoptotic cells are well understood, endogenous or exogenous
factors that regulate Mfge8 expression remain elusive. Here, we describe that
TGFbeta1 increases the expression of Mfge8 and enhances the engulfment of
apoptotic cells by primary mouse microglia in a Mfge8-dependent manner. Further,
apoptotic cells are capable of increasing microglial TGFbeta expression and
release and shift the microglia phenotype toward alternative activation.
Moreover, we provide evidence that Mfge8 expression is differentially regulated
in microglia after classical and alternative activation and that Mfge8 is not
able to exert direct antiinflammatory effects on LPS-treated primary microglia.
Together, these results underline the importance of TGFbeta1 as a regulatory
factor for microglia and suggest that increased TGFbeta1 expression in models of
neurodegeneration might be involved in clearance of apoptotic cells via
regulation of Mfge8 expression.
PMID- 25130374
TI - Bacteriology of pressure ulcers in individuals with spinal cord injury: What we
know and what we should know.
AB - Individuals with spinal cord injury (SCI) are at increased risk for the
development of pressure ulcers. These chronic wounds are debilitating and
contribute to prolonged hospitalization and worse medical outcome. However, the
species of bacteria and the role that specific species may play in delaying the
healing of chronic pressure ulcers in the SCI population has not been well
characterized. This study will review the literature regarding what is known
currently about the bacteriology of pressure ulcers in individuals with SCI. An
electronic literature search of MEDLINE (1966 to February 2014) was performed.
Eleven studies detailing bacterial cultures of pressure ulcers in the SCI
population met inclusion criteria and were selected for review. Among these
studies, bacterial cultures were often polymicrobial with both aerobic and
anaerobic bacteria identified with culture techniques that varied significantly.
The most common organisms identified in pressure ulcers were Staphylococcus
aureus, Proteus mirabilis, Pseudomonas aeruginosa, and Enterococcus faecalis. In
general, wounds were poorly characterized with minimal to no physical description
and/or location provided. Our present understanding of factors that may alter the
microbiome of pressure ulcers in individuals with SCI is quite rudimentary, at
best. Well-designed studies are needed to assess appropriate wound culture
technique, the impact of bacterial composition on wound healing, development of
infection, and the optimum medical and surgical approaches to wound care.
PMID- 25130377
TI - The significance of p40 expression in sclerosing hemangioma of lung.
AB - To explore the histogenesis of cuboidal and polygonal tumor cells in the
sclerosing hemangioma of lung (SHL), eighteen cases of SHL were retrospectively
studied. SPB, p40, TTF-1,EMA,CKpan, vimentin,SMA, CgA,Syn and CD34 were
immunohistochemically labeled by the EnVisionmethod. It was found that the four
main types of structure in SHL were solid,papillary, hemorrhagic and sclerotic
patterns. The tumor cells were composed mainly of two types of cells: cuboidal
tumor cells and polygonal tumor cells. The immunohistochemistry showed that p40
was expressed only in cuboidal tumor cells. TTF-1 and EMA were expressed in both
polygonal cells and cuboidal cells. SPB was also expressed in cuboidal tumor
cells; vimentin was expressed in all polygonal tumor cells and some cuboidal
cells. The findings suggest that the p40-positive cuboidal tumor cells may be
pluripotent original respiratory epithelial cells, with multi-directional
differentiation capacity.
PMID- 25130378
TI - Evidence of inbreeding depression on height, weight, and body mass index: a
population-based child cohort study.
AB - OBJECTIVE: The study was aimed to estimate the effect of inbreeding on height,
weight, and body mass index (BMI) in comparison with non-inbred children.
METHODS: A cohort study was conducted during April 2013 through July 2013 in
Jammu (North India) and a total of 1,270 children (5-15 years of age) were
selected in a random way both from inbred and non-inbred families of five Muslim
populations. The height and weight was measured using standard methods and the
BMI categories were employed as adapted by World Health Organization (WHO).
Family pedigrees were drawn to access the family history and children's inbred
status in terms of coefficient of inbreeding (F). RESULTS: Children of inbred
families showed decline in mean value for height, weight, and BMI (P < 0.0001).
The mean difference (95% confidence interval) in height -7.318 (5.827-8.809),
weight -6.590 (5.100-8.081) and BMI -2.133 (0.6419-3.624) for inbred as compared
with non-inbred children were found to be significant (P < 0.001). We observed an
increase in the difference in mean values for height, weight and BMI with the
increase of inbreeding coefficient and these were statistically significant (P <
0.05, using post hoc tests). The frequency of underweight children was found to
be higher among individuals in the inbred category (<18.5 kg/m(2) = 47.31%) as
compared with the non-inbred category (<18.5 kg/m(2) = 13.41%) and subsequent
depression was found among the inbred children due to an increase of inbreeding
coefficient. CONCLUSIONS: Our results provide the evidence of inbreeding
depression on height, weight, and BMI being important in context of child health.
PMID- 25130379
TI - Mononuclear and terminal zirconium and hafnium methylidenes.
AB - The dimethyl aryloxide complexes [(PNP)M(CH3)2(OAr)] (M=Zr or Hf; PNP(-)=N[2
P(CHMe2)2-4-methylphenyl]2); Ar=2,6-iPr2C6H3), which were readily prepared from
[(PNP)M(CH3)3] by alcoholysis with HOAr, undergo photolytically induced alpha
hydrogen abstraction to cleanly produce complexes [(PNP)M=CH2(OAr)] with terminal
methylidene ligands. These unique systems have been fully characterized,
including the determination of a solid-state structure in the case of M=Zr.
PMID- 25130380
TI - Restrictive food intake as a choice--a paradigm for study.
AB - OBJECTIVE: Inadequate intake and preference for low-calorie foods are salient
behavioral features of Anorexia Nervosa (AN). The neurocognitive mechanisms
underlying pathological food choice have not been characterized. This study aimed
to develop a new paradigm for experimentally modeling maladaptive food choice in
AN. METHOD: Individuals with AN (n = 22) and healthy controls (HC, n = 20)
participated in a computer-based Food Choice Task, adapted for individuals with
eating disorders. Participants first rated 43 food images (including high-fat and
low-fat items) for Healthiness and Tastiness; an item rated neutral on both
blocks was then selected as the Reference item. On each of 42 subsequent trials
participants were asked to choose between the food item presented and the
Reference item. RESULTS: The AN group was less likely to choose high-fat foods
relative to HC, as evidenced both in multilevel logistic regression (z = 2.59, p
= .009) and ANOVA (F(1,39) = 7.80, p = .008) analyses. Health ratings influenced
choice significantly more in AN relative to HC (z = 2.7, p = .006), and were more
related to Taste among AN (chi(2) = 4.10, p = .04). Additionally, taste ratings
declined with duration of illness (r = -.50, p = .02). DISCUSSION: The Food
Choice Task captures the preference for low-fat foods among individuals with AN.
The findings suggest that the experience of tastiness changes over time and may
contribute to perpetuation of illness. By providing an experimental quantitative
measure of food restriction, this task opens the door to new experimental
investigations into the cognitive, affective, and neural factors contributing to
maladaptive food choices characteristic of AN.
PMID- 25130384
TI - Surgery for non-small cell lung cancer in younger patients: what are the
differences?
AB - BACKGROUND: Non-small cell lung cancer (NSCLC) in young adults is uncommon. The
objective of this study was to evaluate the clinicopathological characteristics,
outcomes and prognosis of people younger than 50 years old treated surgically for
NSCLC. METHODS: A retrospective study was conducted using the institutional
database of four thoracic surgery units to collect patients with NSCLC younger
than 50 years who had undergone surgery. These patients were compared with older
patients (>75-years) operated in the same institutions and in the same period.
RESULTS: We identified 113 young patients and 347 older patients. Younger
patients were more likely to be female, non-smokers, with fewer comorbidities.
Younger patients were more likely to be symptomatic at the time of diagnosis.
Risk factors for poor prognosis in younger patients were T-stage, and disease
free-interval less than 548 days. Kaplan-Meier analysis showed a lower five-year
survival in older patients compared with the younger ones (66% vs 38%, p=0.001).
CONCLUSIONS: In conclusion NSCLC in younger patients has some distinct
clinicopathological characteristics. The overall-survival of young patients is
better than in older patients. Young patients receive more complete and
aggressive treatment that could explain better survival. Further prospective
studies with larger patient populations are required, to clarify the biological
and genetic variance of NSCLC in younger patients.
PMID- 25130383
TI - Left ventricular geometry and all-cause mortality in advanced age.
AB - BACKGROUND: Abnormalities of cardiac structure and function are common in a wide
range of populations including those with and without established clinical
cardiovascular disease (CVD). This study reports the prevalence of left
ventricular hypertrophy (LVH), the four patterns of LV geometry and establishes
clinical characteristics and five-year outcomes of each group in people of
advanced age. METHOD: A study conducted in general practices and Maori Health
Services in three New Zealand North Island locations. One hundred participants
had a full clinical echocardiogram performed and analysed in 2008 by one
experienced cardiologist blinded to the participant's clinical history. RESULTS:
Two-thirds of the participants had CVD. Thirty-two participants had
echocardiographic LVH. Those with LVH had higher left atrial area [median (IQR)
26.4cm(2) (10.9) vs. 22.0cm(2) (7.0), p<0.01] and E/e' [median (IQR) 13 (6.8)
vs.10.8 (4.1), p=0.01] than those without LVH. Of those with LVH, 10 demonstrated
concentric hypertrophy (CH) and 22 eccentric hypertrophy (EH); 12 concentric
remodelling (CR) and 40 normal geometry (NG). Both CR and EH were independently
associated with higher risk of all-cause mortality (p<0.01) and hospital
admissions (p<0.05) than those with NG. Those with EH also had a higher risk of
CVD events (p=0.029). CONCLUSIONS: Despite a high prevalence of CVD and
hypertension in this sample, half had normal LV geometry. Concentric remodelling
and eccentric hypertrophy were associated with higher mortality and adverse CVD
outcomes in people of advanced age.
PMID- 25130385
TI - Simulation-based ureteroscopy training: a systematic review.
AB - OBJECTIVE: Simulation is a common adjunct to operative training and various
modalities exist for ureteroscopy. This systematic review aims the following: (1)
to identify available ureteroscopy simulators, (2) to explore evidence for their
effectiveness using characteristic criterion, and (3) to provide recommendations
for simulation-based ureteroscopy training. DESIGN: The preferred reporting items
for systematic reviews and meta-analysis statement guidelines were used. A
literature search was performed using the PubMed, EMBASE, and Cochrane Library
databases. RESULTS: In total, 20 articles concerning ureteroscopy simulators were
included. Overall, 3 high-fidelity bench models are available. The Uro-Scopic
Trainer has demonstrated face, construct, and concurrent validity, whereas the
Scope Trainer has undergone content, construct, and predictive validation. The
adult ureteroscopy trainer has demonstrated face, content, and construct
validity. The URO Mentor is the only available ureteroscopy virtual-reality
system; 10 studies were identified demonstrating its face, content, construct,
concurrent, and predictive validity. The Uro-Scopic Trainer, the Scope Trainer,
and the URO Mentor have demonstrated high educational impact. A noncommercially
available, low-fidelity model has demonstrated effectiveness comparable to its
high-fidelity counterpart at 185 times lesser than the price of the Uro-Scopic
Trainer. The use of porcine models has also been described in 3 studies but
require further study. CONCLUSIONS: Valid models are available for simulation
based ureteroscopy training. However, there is a lack of many high-level studies
conducted, and further investigation is required in this area. Furthermore,
current research focuses on the technical skills acquisition with little research
conducted on nontechnical skills acquisition within ureteroscopy. The next step
for ureteroscopy training is a formalized and validated curriculum, incorporating
simulation, training models, development of nontechnical skills, and real-life
practice.
PMID- 25130386
TI - Research productivity of residents and surgeons with formal research training.
AB - OBJECTIVE: The spectrum of the surgeon-scientist ranges from a clinician who
participates in the occasional research collaboration to the predominantly
academic scientist with no involvement in clinical work. Training surgeon
scientists can involve resource-intense and lengthy training programs, including
Masters and PhD degrees. Despite high enrollment rates in such programs, limited
data exist regarding their outcome. The aim of the study was to investigate the
scientific productivity of general surgeons who completed Masters or PhD graduate
training compared with those who completed clinical residency training only.
DESIGN: A retrospective cohort study of graduates of general surgery residency
was conducted over 2 decades. Data regarding graduation year, dedicated research
training type, as well as publication volume, authorship role, and publication
impact of surgeons during and after training, were analyzed. SETTING: The study
was conducted in 2 general surgery residency training programs in Canada
(University of Alberta and University of Toronto). PARTICIPANTS: A cohort of 323
surgeons who completed general surgery residency between 1998 and 2012. RESULTS:
Overall, 25% of surgeons obtained graduate-level research degrees. Surgeons with
graduate degrees were proportionately more likely to participate in research
publications both during training (100% of PhD, 82% of Masters, and 38% of
clinical-only graduates, p < 0.05) and after training (91% of PhD, 81% of
Masters, and 44% of clinical-only graduates, p < 0.05). Among surgeons involved
in publication, the individual publication volume and impact of publication were
highest among those with PhD degrees, as compared with clinical-only or Masters
training. CONCLUSIONS: The volume and impact of research publication of PhD
trained surgeon-scientists are significantly higher than those having clinical
only and Masters training. The additional 1 or 2 years of training to obtain a
PhD over a Masters degree significantly nurtures trainees to hone research skills
within a supervised environment and should be encouraged for research-inclined
residents.
PMID- 25130387
TI - The right posterior sector graft in living donor liver transplantation revisited.
PMID- 25130388
TI - Suboptimal duration of granulocyte colony-stimulating factor use and chemotherapy
induced neutropenia in women diagnosed with breast cancer.
AB - PURPOSE: Prophylactic use of granulocyte colony-stimulating factor (G-CSF) is
recommended for cancer patients who are at high risk of neutropenic events.
However, whether the clinical effectiveness of G-CSF from randomized controlled
trials translates into "real-world" clinical practice is questionable. The goal
of this retrospective cohort study was to examine the impact of G-CSF prophylaxis
and other potential risk factors of severe neutropenia in women with breast
cancer. METHODS: Our study subjects were women who were diagnosed with breast
cancer and who received a new course of chemotherapy between January 1, 2010, and
December 31, 2010, at a cancer center in Taiwan. Generalized estimating equations
were applied to examine the association between G-CSF prophylaxis and neutropenic
events. FINDINGS: We identified 353 women with breast cancer who received a total
of 2776 cycles of chemotherapy. G-CSF was used as primary prophylaxis in 7% (n =
202) of cycles and as secondary prophylaxis in 11% (n = 319) of cycles. The mean
duration of G-CSF for primary and secondary prophylaxis was 4.9 and 3.7 days,
respectively. A chemotherapy regimen with high risk of febrile neutropenia was
found to be a risk factor for severe neutropenic events (odds ratio, 3.22 [95%
CI, 1.97-5.27]). Prophylactic use of G-CSF was not statistically significantly
associated with febrile neutropenia. IMPLICATIONS: The major determinants of
neutropenic events among patients with breast cancer were the content and
intensity of chemotherapy regimens. Suboptimal use of G-CSF may not be effective
in preventing neutropenic events among women with breast cancer.
PMID- 25130390
TI - Bioactive nanoparticles stimulate bone tissue formation in bioprinted three
dimensional scaffold and human mesenchymal stem cells.
AB - Bioprinting based on thermal inkjet printing is a promising but unexplored
approach in bone tissue engineering. Appropriate cell types and suitable
biomaterial scaffolds are two critical factors to generate successful bioprinted
tissue. This study was undertaken in order to evaluate bioactive ceramic
nanoparticles in stimulating osteogenesis of printed bone marrow-derived human
mesenchymal stem cells (hMSCs) in poly(ethylene glycol)dimethacrylate (PEGDMA)
scaffold. hMSCs suspended in PEGDMA were co-printed with nanoparticles of
bioactive glass (BG) and hydroxyapatite (HA) under simultaneous polymerization so
the printed substrates were delivered with highly accurate placement in three
dimensional (3D) locations. hMSCs interacted with HA showed the highest cell
viability (86.62 +/- 6.02%) and increased compressive modulus (358.91 +/- 48.05
kPa) after 21 days in culture among all groups. Biochemical analysis showed the
most collagen production and highest alkaline phosphatase activity in PEG-HA
group, which is consistent with gene expression determined by quantitative PCR.
Masson's trichrome staining also showed the most collagen deposition in PEG-HA
scaffold. Therefore, HA is more effective comparing to BG for hMSCs osteogenesis
in bioprinted bone constructs. Combining with our previous experience in
vasculature, cartilage, and muscle bioprinting, this technology demonstrates the
capacity for both soft and hard tissue engineering with biomimetic structures.
PMID- 25130391
TI - Can a baseline morning cortisol predict outcome of short Synacthen test in an
endocrine unit in an outpatient setting.
PMID- 25130389
TI - Discoidin domain receptor 2 (DDR2) promotes breast cancer cell metastasis and the
mechanism implicates epithelial-mesenchymal transition programme under hypoxia.
AB - A wide range of genes involved in breast cancer metastasis have been reported to
be related to the microenvironment. We studied the role of discoidin domain
receptor 2 (DDR2), a collagen-binding receptor, in breast cancer progression
under hypoxic conditions. We showed that DDR2 protein expression closely
correlated with the expression of hypoxic marker HIF-1alpha in clinical breast
cancer specimens. The in vitro data demonstrated that hypoxia treatment increased
the levels of both expression and phosphorylation of DDR2 in human breast cancer
cell lines. In vivo, orthotopic breast tumour xenografts with DDR2 knockdown
displayed reduced dissemination and significant prevention in pulmonary and
lymphatic metastasis; conversely, these processes were significantly facilitated
by the enforced expression of the activated form of DDR2. Further mechanism
studies indicated that DDR2 plays an indispensable role in a series of hypoxia
induced behaviours of breast cancer cells, including migration, invasion, and
epithelial-mesenchymal transition (EMT). The transcription factor Snail was found
to mediate DDR2-induced down-regulation of the cell-cell adhesion molecule E
cadherin. It was also documented that there is a correlation between DDR2 and E
cadherin expression with the presence of lymph node metastases in 160 cases of
invasive human breast carcinoma. In addition, we provided evidence that DDR2
silencing in breast cancer cells prevents the hypoxia-induced activation of ERK
MAPK, suggesting its potential involvement in mediating the effect of DDR2 on
hypoxia-induced signalling. Based on the results of this study, we conclude that
DDR2 participates in hypoxia-induced breast cancer metastasis through the
regulation of cell migration, invasion, and EMT, and thus may serve as an
accessible therapeutic target for the treatment of breast cancer.
PMID- 25130392
TI - Serum Cytokine Levels in Behcet's Disease.
AB - BACKGROUND: The aim of this study is to investigate and compare the serum levels
of various cytokines in patients with Behcet's Disease and healthy controls.
METHODS: Thirty-five patients with Behcet's disease and 29 age and sex-matched
healthy controls were included in the study. The patients were separated into
groups with active and inactive disease. Serum IL-2, IL-6, IL-8, IL-10, IL-17A,
and IFN-gamma levels were determined using the enzyme-linked immunosorbent assay
method. Cytokine levels of the two patient groups and healthy controls were
compared using SPSS 15.0. RESULTS: Ten patients with active disease and 25
patients with inactive disease were present. Serum IL-8 levels of active BD
patients were higher compared to inactive patients (P = 0.048) and healthy
controls (P = 0.02). IL-8 levels were correlated with the duration of symptoms (r
= 0.490, P = 0.003) and time passed since diagnosis (r = 0.579, P ? 0.001).
CONCLUSION: Behcet's disease involves complex interactions of cells of the immune
system, mainly T lymphocytes and neutrophils. Further studies on the cytokine
profile in Behcet's disease will aid in elucidation of its pathogenesis.
PMID- 25130393
TI - Identification of binding sites for C-terminal pro-gastrin-releasing peptide
(GRP)-derived peptides in renal cell carcinoma: a potential target for future
therapy.
AB - OBJECTIVE: To determine the expression and biology of the neuroendocrine growth
factor gastrin-releasing peptide (GRP) and other proGRP-derived peptides in renal
cancer. MATERIALS AND METHODS: Receptor binding studies, enzyme-linked
immunosorbent assay (ELISA) and radioimmunoassay, were used to quantitate the
presence of proGRP-derived peptide receptors and their ligands in renal cancer
cell lines and human renal cancers. Biological activity of proGRP peptides was
confirmed with proliferation, migration, and extracellular-signal-regulated
kinases 1 and 2 (ERK1/2) activation assays in vitro. In vivo, ACHN renal cancer
xenografts were treated with proGRP-derived peptides to assess tumour size and
necrosis. hypoxia-inducible factor 1alpha (HIF1alpha) and vascular endothelial
growth factor (VEGF) expression were investigated with Western blotting and ELISA
respectively, to determine the possible contribution of the proGRP peptides to
tumour viability. RESULTS: In ACHN cells that expressed both proGRP- and GRP
receptors, the expression of proGRP binding sites was 80-fold greater than the
GRP-receptor (GRPR). C-terminal proGRP-derived peptides stimulated the activation
of ERK1/2, but with a different time course to GRP, consistent with the
suggestion that these peptides may have unique cellular functions. Both GRP and
proGRP47-68 stimulated proliferation and migration of ACHN cells in vitro, but
only GRP reduced the extent of tumour necrosis in ACHN xenografts. GRP, but not
proGRP47-68, was able to induce HIF1alpha and VEGF expression in ACHN cells. This
may account in part for the reduction in necrosis after GRP treatment. C-terminal
proGRP-derived peptides were present in all three renal cancer cell lines and a
panel of human renal cancers, but mature amidated GRP was absent. CONCLUSION: C
terminal proGRP peptides are more abundant in renal cancers and their cell lines
than the more extensively studied amidated peptide, GRP. These results suggest
that C-terminal proGRP-derived peptides may be a better target for novel renal
cancer treatments.
PMID- 25130394
TI - Histone H1.5, a novel prostatic cancer marker: an immunohistochemical study.
AB - Histone H1.5 (HH1.5) is a somatic subtype of the histone H1 family of linker
proteins that are located in the nucleus and play a role in stabilizing higher
order chromatin structure, gene expression, DNA repair, and cell proliferation.
Recently, differential immunohistochemical expression of HH1.5 has been found in
various neuroendocrine neoplasms. This study aimed to investigate the
immunohistochemical expression of HH1.5 in prostatic adenocarcinomas. Sixty-three
prostate needle core biopsies, 9 radical prostatectomy specimens, and 3
metastatic prostate cancer cases were evaluated. HH1.5 immunohistochemistry
revealed strong nuclear reactivity in 68 (93%) of 73 cases of prostate
adenocarcinomas, compared to only 7 (9%) of 75 cases of benign prostatic glands
(P <= .0001). In all positive benign prostate epithelium, HH1.5 was limited to
focal and weak reactivity. Similarly, all 23 foci of high-grade prostatic
intraepithelial neoplasia exhibited focal staining, with the vast majority having
only weak nuclear reactivity. Increased HH1.5 reactivity was observed in Gleason
patterns 4 and 5 as compared to Gleason pattern 3, 72% and 56%, respectively (P
<= .02). All 3 metastatic prostate cancer cases showed strong nuclear reactivity.
HH1.5 may be a useful diagnostic tool in evaluating prostatic biopsies,
particularly with small foci of cancer. Further studies are needed to support
these findings and investigate the possible prognostic significance of HH1.5 in
prostatic adenocarcinomas.
PMID- 25130395
TI - Protein expression of the chemokine receptor CXCR4 and its ligand CXCL12 in
primary cutaneous melanoma--biomarkers of potential utility?
AB - Dysregulation of the CXCR4/CXCL12 axis, relevant in melanoma progression,
activates cell cycle progression and migration via stimulation of the MAPK
pathway. We sought to ascertain the cooperativity of the CXCR4/CXCL12 axis with
established prognosticators and BRAF status in melanoma. Samples (n = 107) of
primary cutaneous melanoma were assessed for protein expression of CXCR4 and
CXCL12, and molecular analyses were performed to ascertain BRAF status.
Univariate analyses of CXCR4 protein showed that the proportion of CXCR4
positives was greater in melanomas with absence of mitoses (P < .0001), absence
of ulceration (P = .0008), and absence of regression (P = .02). Patients
presenting at shallower stages (American Joint Committee on Cancer [AJCC] 1-2)
exhibited a larger proportion of CXCR4 positives (76.9%, P < .0001 and 69.0%, P =
.008), whereas those at deeper stages (AJCC 3-4) exhibited a larger proportion of
negatives (75.0%, P = .004 and 66.7%, P = .22). In a multivariate analysis, lower
odds of CXCR4 protein expression were associated with AJCC stage 3 (odds ratio
[OR]=0.16, P = .01), AJCC stage 4 (OR=0.17, P = .04), and mitoses (OR=0.21, P =
.01). Univariate analyses of CXCL12 protein showed that the proportion of CXCL12
negatives was significantly smaller in melanomas with depth of at least 1 mm,
absence of ulceration, and absence of vascular invasion (P < .0001 for all).
CXCR4 and CXCL12 appear to be biomarkers associated with established
prognosticators of good and poor clinical outcome, respectively, in primary
cutaneous melanoma. A BRAF mutation does not appear to be associated with
CXCR4/CXCL12 axis upregulation in primary cutaneous melanoma.
PMID- 25130396
TI - Multiple metastases from histologically benign intraarticular diffuse-type
tenosynovial giant cell tumor: a case report.
AB - Diffuse-type tenosynovial giant cell tumor (D-TGCT) is a relatively rare
mesenchymal tumor. It is a locally aggressive but virtually nonmetastasizing
neoplasm and thus regarded as benign. Only a few D-TGCTs with benign histology
have been reported to metastasize. We report an extremely rare case of benign D
TGCT in which multiple metastases developed 9 years after surgery for the primary
tumor. The present case suggests that conventional D-TGCT has the potential to
form distant metastases, albeit exceptionally rarely, and that this probable
implantation phenomenon can be managed conservatively.
PMID- 25130397
TI - Recent progress in analytical capillary isotachophoresis.
AB - This paper brings a survey of papers on analytical capillary ITP published since
2012 until the first quarter of 2014. These papers are ranged according to their
nature, the techniques used, and the instrumentation employed. The sequence of
the related chapter titles is as follows: Theory and simulations, techniques and
instrumentation, single-column and column-switching applications of ITP, ITP in
microfluidic systems, on-line ITP-CZE and transient ITP (tITP) techniques and
applications. The review shows the position of analytical capillary ITP among
contemporary separation techniques and implies the potential future trends.
PMID- 25130398
TI - Nonreproductive role of gonadotropin-releasing hormone in the control of ascidian
metamorphosis.
AB - BACKGROUND: Gonadotropin-releasing hormones (GnRHs) are neuropeptides that play
central roles in the reproduction of vertebrates. In the ascidian Ciona
intestinalis, GnRHs and their receptors are expressed in the nervous systems at
the larval stage, when animals are not yet capable of reproduction, suggesting
that the hormones have non-reproductive roles. RESULTS: We showed that GnRHs in
Ciona are involved in the animal's metamorphosis by regulating tail absorption
and adult organ growth. Absorption of the larval tail and growth of the adult
organs are two major events in the metamorphosis of ascidians. When larvae were
treated with GnRHs, they completed tail absorption more frequently than control
larvae. cAMP was suggested to be a second messenger for the induction of tail
absorption by GnRHs. tGnRH-3 and tGnRH-5 (the "t" indicates "tunicate") inhibited
the growth of adult organs by arresting cell cycle progression in parallel with
the promotion of tail absorption. CONCLUSIONS: This study provides new insights
into the molecular mechanisms of ascidian metamorphosis conducted by non
reproductive GnRHs.
PMID- 25130399
TI - Mitochondrial complex I activity suppresses inflammation and enhances bone
resorption by shifting macrophage-osteoclast polarization.
AB - Mitochondrial complex I (CI) deficiency is associated with multiple neurological
and metabolic disorders. However, its effect on innate immunity and bone
remodeling is unclear. Using deletion of the essential CI subunit Ndufs4 as a
model for mitochondrial dysfunction, we report that mitochondria suppress
macrophage activation and inflammation while promoting osteoclast differentiation
and bone resorption via both cell-autonomous and systemic regulation. Global
Ndufs4 deletion causes systemic inflammation and osteopetrosis. Hematopoietic
Ndufs4 deletion causes an intrinsic lineage shift from osteoclast to macrophage.
Liver Ndufs4 deletion causes a metabolic shift from fatty acid oxidation to
glycolysis, accumulating fatty acids and lactate (FA/LAC) in the circulation.
FA/LAC further activates Ndufs4(-/-) macrophages via reactive oxygen species
induction and diminishes osteoclast lineage commitment in Ndufs4(-/-)
progenitors; both inflammation and osteopetrosis in Ndufs4(-/-) mice are
attenuated by TLR4/2 deletion. Together, these findings reveal mitochondrial CI
as a critical rheostat of innate immunity and skeletal homeostasis.
PMID- 25130400
TI - FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure,
and weight loss.
AB - The mechanism by which pharmacologic administration of the hormone FGF21
increases energy expenditure to cause weight loss in obese animals is unknown.
Here we report that FGF21 acts centrally to exert its effects on energy
expenditure and body weight in obese mice. Using tissue-specific knockout mice,
we show that betaKlotho, the obligate coreceptor for FGF21, is required in the
nervous system for these effects. FGF21 stimulates sympathetic nerve activity to
brown adipose tissue through a mechanism that depends on the neuropeptide
corticotropin-releasing factor. Our findings provide an unexpected mechanistic
explanation for the strong pharmacologic effects of FGF21 on energy expenditure
and weight loss in obese animals.
PMID- 25130402
TI - The structure of the gas bladder of the spotted gar, Lepisosteus oculatus.
AB - We report here on the macroscopic, light microscopic, and electron microscopic
structure of the gas bladder (GB) of the spotted gar, Lepisosteus oculatus. The
GB opens into the pharynx, dorsal to the opening of the oesophagus, through a
longitudinal slit bordered by two glottal ridges. Caudal to the ridges, the GB is
an elongated sac divided into a central duct and right and left lobes. The lobes
are formed by a cranio-caudal sequence of large air spaces that open into the
central duct. The structure of the GB is that of a membranous sac supported by a
system of septa arising from the walls of a central duct. The septa contain
variable amounts of striated and smooth muscle might function to maintain the
bladder shape and in providing contractile capabilities. The presence of muscle
cells, nerves, and neuroepithelial cells in the wall of the GB strongly suggests
that GB function is tightly regulated. The central duct and the apical surface of
the thickest septa are covered by mucociliated epithelium. Most of the rest of
the inner bladder surface is covered by a respiratory epithelium which contains
goblet cells and a single type of pneumocyte. These two cell types produce
surfactant. The respiratory barrier contains thick areas with fibrillar material
and cell prolongations, and thin areas that only contain basement membrane
material between the capillary wall and the respiratory epithelium. Lungs and GBs
share many anatomical and histological features. There appears to be no clear
criterion for structural distinction between these two types of respiratory
organs.
PMID- 25130404
TI - Bedside interprofessional rounds: perceptions of benefits and barriers by
internal medicine nursing staff, attending physicians, and housestaff physicians.
AB - BACKGROUND: Interprofessional collaboration improves the quality of care, but
integration into workflow is challenging. Although a shared conceptualization
regarding bedside interprofessional rounds may enhance implementation, little
work has investigated providers' perceptions of this activity. OBJECTIVE: To
evaluate the perceptions of nurses, attending physicians, and housestaff
physicians regarding the benefits/barriers to bedside interprofessional rounds.
DESIGN AND PARTICIPANTS: Observational, cross-sectional survey of hospital-based
medicine nurses, attending physicians, and housestaff physicians. Descriptive,
nonparametric Wilcoxon rank sum and nonparametric correlation were used. MAIN
MEASURES: Bedside interprofessional rounds were defined as "encounters including
2 physicians plus a nurse or other care provider discussing the case at the
patient's bedside." Eighteen items related to "benefits" and 21 items related to
"barriers" associated with bedside interprofessional rounds. RESULTS: Of 171
surveys sent, 149 were completed (87%). Highest-ranked benefits were related to
communication/coordination, including "improves communication between nurses
physicians;" lowest-ranked benefits were related to efficiency, process, and
outcomes, including "decreases length-of-stay" and "improves timeliness of
consultations." Nurses reported most favorable ratings for all items (P < 0.05).
Rank order for 3 provider groups showed high correlation (r = 0.92, P < 0.001).
Highest-ranked barriers were related to time, including "nursing staff have
limited time;" lowest-ranked barriers were related to provider- and patient
related factors, including "patient lack of comfort." Rank order of barriers
among all groups showed moderate correlation (r = 0.62-0.82). CONCLUSIONS:
Although nurses perceived greater benefit for bedside interprofessional rounds
than physicians, all providers perceived coordination/teamwork benefits higher
than outcomes. To the extent the results are generalizable, these findings lay
the foundation for facilitating meaningful patient-centered interprofessional
collaboration.
PMID- 25130403
TI - Malignant peripheral nerve sheath tumors (MPNST): a SEER analysis of incidence
across the age spectrum and therapeutic interventions in the pediatric
population.
AB - BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are very rare in the
general population and challenging to treat. A paucity of data exists regarding
the incidence of MPNST across all age groups and treatment outcomes in the
pediatric population. We aimed to characterize both using the Survival,
Epidemiology, and End Results (SEER) database. PROCEDURE: The SEER-18 database
with information on the United States population from 1973 to 2009 was queried
for cases of MPNST. For incidence data, 1,182 cases were found among the general
population. Of those, 165 cases were in individuals aged 0-19. After exclusions,
139 cases from the SEER-18 database met study criteria for outcomes analysis. For
each patient, variables including gender, age, race, stage (localized, regional,
or distant), surgical treatment, and radiotherapy were obtained. RESULTS: The
overall incidence of MPNST was 1.46 per million person-years, with increased
incidence among the elderly. In the pediatric population, the incidence was 0.56
per million person-years, and was higher among post-pubertal children aged 10-19.
Median overall survival in the pediatric population was 30 months, with only
localized disease and treatment with surgery being positive prognostic factors on
multivariate analysis. CONCLUSIONS: MPNST is a rare disease and, among children,
is most frequent seen in adolescents. Surgery is crucial as first-line treatment
for MPNST, especially if the tumor is localized at diagnosis. In patients with
non-localized MPNST, the disease remains extremely difficult to manage, and both
surgery and radiotherapy are interventions that should be considered.
PMID- 25130405
TI - Increased NT-proANP predicts risk of congestive heart failure in Cavalier King
Charles spaniels with mitral regurgitation caused by myxomatous valve disease.
AB - OBJECTIVES: To evaluate the predictive value of plasma N-terminal pro-atrial
natriuretic peptide (NT-proANP) and nitric oxide end-products (NOx) as markers
for progression of mitral regurgitation caused by myxomatous mitral valve
disease. ANIMALS: Seventy-eight privately owned Cavalier King Charles spaniels
with naturally occurring myxomatous mitral valve disease. METHODS: Prospective
longitudinal study comprising 312 measurements over a 4.5 year period. Clinical
values were recorded, NT-proANP concentrations were measured by radioimmunoassay,
and NOx were analyzed colorimetrically. To predict congestive heart failure
(CHF), Cox proportional hazards models with time-varying covariates were
constructed. RESULTS: The hazard ratio for NT-proANP (per 1000 pmol/l increase)
to predict future CHF was 6.7 (95% confidence interval, 3.6-12.5; p < 0.001). The
median time to CHF for dogs with NT-proANP levels >1000 pmol/l was 11 months (95%
confidence interval, 5.6-12.6 months), compared to 54 months (46 - infinity) for
dogs with concentrations <= 1000 pmol/l (p < 0.001). Due to intra- and inter
individual variability, most corresponding analyses for NOx were insignificant
but dogs reaching CHF had a lower mean NOx concentration than dogs not reaching
CHF (23 vs. 28 MUmol/l, p = 0.016). Risk of CHF increased with increase in heart
rate (>130 beats per minute) and grade of murmur (>= 3/6). CONCLUSIONS: The risk
of CHF due to mitral regurgitation is increased in dogs with blood NT-proANP
concentrations above 1000 pmol/l. Measurement of NT-proANP can be a valuable tool
to identify dogs that may develop CHF within months.
PMID- 25130406
TI - Atrial septal pacing in small dogs: a pilot study.
AB - OBJECTIVE: To determine the feasibility of atrial septal pacing via a delivery
catheter-guided small non-retracting helix pacing lead. ANIMALS: Six healthy
beagles (8.3-12.9 kg). METHODS: Using single plane fluoroscopic guidance,
Medtronic((r)) 3830 SelectSecure leads were connected to the atrial septum via
Medtronic(r) Attain Select(r) II standard 90 Left Heart delivery catheter. Pacing
threshold and lead impedance were measured at implantation. The Wenckebach point
was tested via atrial pacing up to 220 paced pulses per minute (ppm). Thoracic
radiographs were performed following implantation to identify the lead position,
and repeated at 24 h, 1 month, and 3 months post-operatively. RESULTS: Macro-lead
dislodgement occurred in two dogs at 24 h and in three dogs at one-month post
implantation. Lead impedance, measured at the time of implantation, ranged from
583 to 1421 Omega. The Wenckebach point was >220 ppm in four of the six dogs. The
remaining two dogs had Wenckebach points of 120 and 190 ppm. CONCLUSIONS: This
pilot study suggests the selected implantation technique and lead system were
inadequate for secure placement in the atrial septum of these dogs. The possible
reasons for inadequate stability include unsuitable lead design for this
location, inadequate lead slack at the time of implantation and inadequate
seating of the lead as evidenced by low impedance at the time of implantation.
Other implantation techniques and/or pacing leads should be investigated to
determine the optimal way of pacing the atria in small breed dogs that are prone
to sinus node dysfunction.
PMID- 25130401
TI - A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and
efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and
rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects
with relapsed chronic lymphocytic leukaemia.
AB - Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of
chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with
lumiliximab alone and in combination with fludarabine, cyclophosphamide and
rituximab (FCR) established its potential efficacy and tolerability. The 152CL201
trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus
FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized
(1:1), open-label, multicentre study of lumiliximab in combination with FCR
versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven
patients were randomized to either arm. Overall the combination of lumiliximab
with FCR was not significantly better than FCR alone (overall response rate 71%
vs. 72%, complete response rate 16% vs. 15%, median progression-free survival
24.6 vs. 23.9 months respectively, for FCR with and without lumiliximab). There
was a slightly increased incidence of adverse events with lumiliximab but these
increases did not appear to lead to differences in eventual outcomes. An interim
analysis failed to show sufficient efficacy of the combination of lumiliximab
with FCR. The study was therefore stopped early for lack of efficacy. Despite the
eventual outcome, the LUCID trial is one of the largest studies that provides
valuable insight into the efficacy and tolerability of FCR as a therapeutic
option for patients with relapsed CLL.
PMID- 25130408
TI - A quantitative geometric mechanics lens model: insights into the mechanisms of
accommodation and presbyopia.
AB - This study expands on a geometric model of ocular accommodation (Reilly and Ravi,
Vision Res. 50:330-336; 2010) by relaxing assumptions regarding lens symmetry
about the equator. A method for predicting stretching force was derived. Two
models were then developed: Model 1 held the equatorial geometry constant at all
stages of accommodation, while Model 2 allowed localized deformation at the
equator. Both models were compared to recent data for axial thickness, anterior
and posterior radii of curvature, surface area, cross-sectional area, volume, and
stretching force for the 29-year-old lens. Age-related changes in accommodation
were also simulated. Model 1 gave predictions which agreed with the Helmholtz
theory of accommodation, while Model 2's predictions agreed with the Schachar
mechanism of accommodation. Trends predicted by Model 1 agreed with all available
experimental data, while Model 2 disagreed with recent surface area measurements.
Further analysis indicated that Model 1 was fundamentally more efficient in that
it required less force per diopter change in optical power than Model 2. Model 1
more accurately predicted age-related changes in accommodation amplitude. This
implies that the zero-force (fully accommodated) state geometry changes with age
due to a shifting balance in residual stresses between the lens and capsule.
PMID- 25130407
TI - How shape from contours affects shape from shading.
AB - The spatial pattern of reflected light carries detailed but ambiguous information
about 3D shapes of illuminated objects. A little studied factor that affects the
perceived 3D relief of 2D shaded figures is the shape of their contours. An
experiment is reported in which 102 subjects matched twelve contoured grating
displays (horizontal three-cycle gratings with variously shaped top and bottom
contours) with perspective line drawings of different 3D shapes, and also judged
their depth extent and direction of illumination. The results showed that contour
shapes can have surprisingly strong and salient effects on perceived relief. For
each display there was a dominant matching drawing, chosen by the largest
percentage of subjects, which varied from 95% to 26% across the set of displays.
The luminance distribution of contoured gratings is essentially 1D, so that,
compared to the general 2D case, their mathematical analysis is considerably
simplified, and shape can in certain cases be recovered from shading in
analytical form, yielding a three-parameter family of solutions. An analysis of
subject responses showed that most reported reliefs had shapes which were closely
related to members of the solution family. Furthermore, the particular perceived
shapes of contoured gratings could with some success be predicted from the shapes
of their contours, based on a simple shape-from-contours rule. However, the data
also indicated the presence of a convexity tendency, independent from contour
shape.
PMID- 25130409
TI - Efficiency of electronically monitored amblyopia treatment between 5 and 16 years
of age: new insight into declining susceptibility of the visual system.
AB - The notion of a limited, early period of plasticity of the visual system has been
challenged by more recent research demonstrating functional enhancement even into
adulthood. In amblyopia ("lazy eye") it is still unclear to what extent the
reduced effect of treatment after early childhood is due to declining plasticity
or lower compliance with prescribed patching. The aim of this study was to
determine the dose-response relationship and treatment efficiency from acuity
gain and electronically recorded patching dose rates, and to infer from these
parameters on a facet of age dependence of functional plasticity related to
occlusion for amblyopia. The Occlusion Dose Monitor was used to record occlusion
in 27 participants with previously untreated strabismic and/or anisometropic
amblyopia aged between 5.4 and 15.8 (mean 9.2) years during 4months of
conventional treatment. Group data showed improvement of acuity throughout the
age span, but significantly more in patients younger than 7years despite
comparable patching dosages. Treatment efficiency declined with age, with the
most pronounced effects before the age of 7years. Thus, electronic recording
allowed this first quantitative insight into occlusion treatment spanning the age
range from within to beyond the conventional age for patching. Though
demonstrating improvement in over 7year old patients, it confirmed the importance
of early detection and treatment of amblyopia. Treatment efficiency is presented
as a tool extending insight into age-dependent functional plasticity of the
visual system, and providing a basis for comparisons of effects of patching vs.
emerging alternative treatment approaches for amblyopia.
PMID- 25130410
TI - Bias corrected double judgment accuracy during spatial attention cueing: unmasked
stimuli with non-predictive and semi-predictive cues.
AB - The present experiments indicate that in a 7-AFC double judgment accuracy task
with unmasked stimuli, cue location response bias can be quantified and removed,
revealing unbiased improvements in response accuracy for valid cues compared to
invalid cues. By testing for cueing effects over a range of contrast levels with
unmasked stimuli, changes in the psychometric function were examined and provide
insight into the mechanisms of involuntary attention which might account for the
observed cueing effects. Cue validity was varied between two separate experiments
showing that non-predictive (14.3%) and moderately-predictive cues (50%) equally
facilitate stimulus identification and localization during transient involuntary
attention capture. Observers had improved accuracy at identifying both the
location and the feature identity of target letters throughout a range of
contrast levels, without any dependence on backward masking. There was a leftward
shift of the psychometric function threshold with valid cued data and no slope
reduction suggesting that any additive hypothesis based on spatial uncertainty
reduction or perceptual enhancement is not a sufficient explanation for the
observed cueing effects. The interdependence of the perceptual processes of
stimulus discrimination and localization were also investigated by analyzing
response contingencies, showing that observers were equally skilled at making
identification and localization accuracy judgments with unmasked stimuli.
PMID- 25130411
TI - Identification of phenanthrene derivatives in Aerides rosea (Orchidaceae) using
the combined systems HPLC-ESI-HRMS/MS and HPLC-DAD-MS-SPE-UV-NMR.
AB - INTRODUCTION: In our continued efforts to contribute to the general knowledge on
the chemical diversity of orchids, we have decided to focus our investigations on
the Aeridinae subtribe. Following our previous phytochemical study of Vanda
coerulea, which has led to the identification of phenanthrene derivatives, a
closely related species, Aerides rosea Lodd. ex Lindl. & Paxton, was chosen for
investigation. OBJECTIVE: To identify new secondary metabolites, and to avoid
isolation of those already known, by means of the combined systems HPLC-DAD(diode
array detector) with high-resolution tandem mass spectrometry (HRMS/MS) and HPLC
DAD-MS-SPE(solid-phase extraction)-UV-NMR. METHODS: A dereplication strategy was
developed using a HPLC-DAD-HRMS/MS targeted method and applied to fractions from
A. rosea stem extract. Characterisation of unknown minor compounds was then
performed using the combined HPLC-DAD-MS-SPE-UV-NMR system. RESULTS: The
dereplication method allowed the characterisation of four compounds (gigantol,
imbricatin, methoxycoelonin and coelonin), previously isolated from Vanda
coerulea stem extract. The analyses of two fractions permitted the identification
of five additional minor constituents including one phenanthropyran, two
phenanthrene and two dihydrophenanthrene derivatives. The full set of NMR data of
each compound was obtained from microgram quantities. CONCLUSION: Nine secondary
metabolites were characterised in A. rosea stems, utilising HPLC systems combined
with high-resolution analytical systems. Two of them are newly described
phenanthrene derivatives: aerosanthrene (5-methoxyphenanthrene-2,3,7-triol) and
aerosin (3-methoxy-9,10-dihydro-2,5,7-phenanthrenetriol).
PMID- 25130412
TI - Neoadjuvant chemotherapy followed by surgery in very locally advanced technically
unresectable oral cavity cancers.
AB - BACKGROUND: The median survival of technically unresectable oral-cavity cancers
(T4a and T4b) with non surgical therapy is 2-12 months. We hypothesized that
neoadjuvant chemotherapy (NACT) could reduce the tumour size and result in
successful resection and ultimately improved outcomes. We present a retrospective
analysis of consecutive patients who received NACT at our centre between January
2008 and August 2012. PATIENTS AND METHODS: All patients with technically
unresectable oral cancers were assessed in a multidisciplinary clinic and
received 2 cycles of NACT. After 2 cycles, patients were reassessed and planned
for either surgery with subsequent CTRT or nonsurgical therapy including CT-RT,
RT or palliation. SPSS version 16 was used for analysis of locoregional control
and overall survival (OS). Univariate and multivariate analysis was done for
factors affecting the OS. RESULTS: 721 patients with stage IV oral-cavity cancer
received NACT. 310 patients (43%) had sufficient reduction in tumour size and
underwent surgical resection. Of the remaining patients, 167 received
chemoradiation, 3 radical radiation and 241 palliative treatment alone The
locoregional control rate at 24 months was 20.6% for the overall cohort, 32% in
patients undergoing surgery and 15% in patients undergoing non surgical treatment
(p=0.0001). The median estimated OS in patients undergoing surgery was 19.6
months (95% CI, 9.59-25.21 months) and 8.16 months (95%, CI 7.57-8.76) in
patients treated with non surgical treatment (p=0.0001). CONCLUSION: In our
analysis, NACT led to successful resection and improved overall survival in a
significant proportion of technically unresectable oral-cancer patients.
PMID- 25130413
TI - Oral health, dental care and mouthwash associated with upper aerodigestive tract
cancer risk in Europe: the ARCAGE study.
PMID- 25130414
TI - Correlation between chronic inflammation and oral squamous cell carcinoma (OSCC).
PMID- 25130415
TI - Labeled protein recognition at a membrane bilayer interface by embedded synthetic
receptors.
AB - Self-folding deep cavitands embedded in a supported lipid bilayer are capable of
recognizing suitably labeled proteins at the bilayer interface. The addition of a
choline derived binding "handle" to a number of different proteins allows their
selective noncovalent recognition, with association constants on the order of
10(5) M(-1). The proteins are displayed at the water:bilayer interface, and a
single binding handle allows recognition of the large, charged protein by a small
molecule synthetic receptor via complementary shape and charge interactions.
PMID- 25130417
TI - Polysomnography: assessment of decannulation readiness in chronic upper airway
obstruction.
AB - OBJECTIVES/HYPOTHESIS: To evaluate the clinical value of polysomnography in
patients with a tracheotomy due to chronic upper airway obstruction prior to
attempting decannulation. STUDY DESIGN: Retrospective chart review. METHODS:
Subjects with chronic upper airway obstruction were identified using a clinical
database between 2000 and 2014. All subjects had a tracheotomy, were assessed by
the senior author in a tertiary care academic center, and underwent
polysomnography prior to attempting decannulation. Patients were excluded if they
did not undergo polysomnography or had severe obstructive sleep apnea as the
primary indication for tracheotomy. RESULTS: Fifteen patients were identified.
The majority (87.5%) of patients were successfully decannulated after their first
polysomnography showed acceptable results when carried out with the tracheotomy
occluded. Obstructive sleep apnea was identified in four of the nine patients who
tolerated overnight tracheotomy occlusion, and continuous positive airway
pressure (CPAP) was initiated. An additional four of the remaining six patients
were decannulated after subsequent polysomnography demonstrated improvement with
CPAP, and two required an additional airway procedure. CONCLUSIONS: Chronic upper
airway obstruction requiring tracheotomy can be challenging to treat and
successfully decannulate. Indirect laryngoscopy is essential to evaluate the
anatomy of the larynx; however, it cannot assess potential increased obstruction
during sleep. The study indicates that polysomnography can assist with the
evaluation of decannulation readiness in patients with chronic upper airway
obstruction as an adjunct measure in addition to imaging and laryngoscopy. LEVEL
OF EVIDENCE: 4.
PMID- 25130418
TI - Ultrathin core-sheath fibers for liposome stabilization.
AB - Ultrathin core-sheath fibers with small unilamellar vesicles (SUVs) in the core
were prepared by coaxial electrospinning. SUVs/sodium hyaluranate (HA-Na)/water
and polyvinylpyrrolidone (PVP)/ethanol solutions were used as core and sheath
fluid in electrospinning, respectively. The ultrathin fibers were characterized
by scanning and transmission electron microscopy (SEM and TEM) and laser scanning
confocal microscopy (LSCM). The SUVs were successfully encapsulated in the core
HA-Na matrix of the ultrathin fibers and are in the elliptic shape. The SUVs
encapsulated in the core matrix of the ultrathin fibers have an excellent
stability. The SUVs embedded in the ultrathin fibers are stable. When the
ultrathin fibers were re-dissolved in water after one-month storage at room
temperature, the rehydrated SUVs have the similar size and size distribution as
the as-prepared SUVs. The liposome-loaded ultrathin fiber mats have the promising
applications in wound healing materials.
PMID- 25130416
TI - Modeling the effects of sensory reinforcers on behavioral persistence with
alternative reinforcement.
AB - Problem behavior often has sensory consequences that cannot be separated from the
target response, even if external, social reinforcers are removed during
treatment. Because sensory reinforcers that accompany socially mediated problem
behavior may contribute to persistence and relapse, research must develop analog
sensory reinforcers that can be experimentally manipulated. In this research, we
devised analogs to sensory reinforcers in order to control for their presence and
determine how sensory reinforcers may impact treatment efficacy. Experiments 1
and 2 compared the efficacy of differential reinforcement of alternative behavior
(DRA) versus noncontingent reinforcement (NCR) with and without analog sensory
reinforcers in a multiple schedule. Experiment 1 measured the persistence of key
pecking in pigeons, whereas Experiment 2 measured the persistence of touchscreen
responses in children with intellectual and developmental disabilities. Across
both experiments, the presence of analog sensory reinforcers increased the
levels, persistence, and variability of responding relative to when analog
sensory reinforcers were absent. Also in both experiments, target responding was
less persistent under conditions of DRA compared to NCR regardless of the
presence or absence of analog sensory reinforcers.
PMID- 25130419
TI - Delphinid systematics and biogeography with a focus on the current genus
Lagenorhynchus: multiple pathways for antitropical and trans-oceanic radiation.
AB - The six species currently classified within the genus Lagenorhynchus exhibit a
pattern of antitropical distribution common among marine taxa. In spite of their
morphological similarities they are now considered an artificial grouping, and
include both recent and the oldest representatives of the Delphinidae radiation.
They are, therefore, a good model for studying questions about the evolutionary
processes that have driven dolphin speciation, dispersion and distribution. Here
we used two different approaches. First we constructed a multigenic phylogeny
with a minimum amount of missing data (based on 9 genes, 11,030bp, using the 6
species of the genus and their closest relatives) to infer their relationships.
Second, we built a supermatrix phylogeny (based on 33 species and 27 genes) to
test the effect of taxon sampling on the phylogeny of the genus, to provide
inference on biogeographic history, and provide inference on the main events
shaping the dispersion and radiation of delphinids. Our analyses suggested an
early evolutionary history of marine dolphins in the North Atlantic Ocean and
revealed multiple pathways of migration and radiation, probably guided by
paleoceanographic changes during the Miocene and Pliocene. L. acutus and L.
albirostris likely shared a common ancestor that arose in the North Atlantic
around the Middle Miocene, predating the radiation of subfamilies Delphininae,
Globicephalinae and Lissodelphininae.
PMID- 25130420
TI - Highly sensitive assay for acetylcholinesterase activity and inhibition based on
a specifically reactive photonic nanostructure.
AB - Assays for acetylcholinesterase (AChE) with high sensitivity and high selectivity
as well as facile manipulation have been urgently required in various fields. In
this work, a reaction-based photonic strategy was developed for the efficient
assay of AChE activity and inhibition based on the synergetic combination of the
specific thiol-maleimide addition reaction with photonic porous structure. It was
found that various applications including detection of AChE activity, measurement
of the related enzymatic kinetics, and screening of inhibitors could be
efficiently implemented using such strategy. Remarkably, the unique photonic
nanostructure endows the constructed sensing platform with high sensitivity with
a limit of detection (LOD) of 5 mU/mL for AChE activity, high selectivity, and
self-reporting signaling. Moreover, the label-free solid film-based sensing
approach described here has advantages of facile manipulation and bare-eye
readout, compared with conventional liquid-phase methods, exhibiting promising
potential in practical application for the AChE assay.
PMID- 25130422
TI - A dogma-breaking concept: glutamate oxidation in astrocytes is the source of
lactate during aerobic glycolysis in resting subjects.
PMID- 25130421
TI - The longitudinal effects of physical activity and dietary calcium on bone mass
accrual across stages of pubertal development.
AB - Childhood and adolescence are critical periods of bone mineral content (BMC)
accrual that may have long-term consequences for osteoporosis in adulthood.
Adequate dietary calcium intake and weight-bearing physical activity are
important for maximizing BMC accrual. However, the relative effects of physical
activity and dietary calcium on BMC accrual throughout the continuum of pubertal
development in childhood remains unclear. The purpose of this study was to
determine the effects of self-reported dietary calcium intake and weight-bearing
physical activity on bone mass accrual across the five stages of pubertal
development in a large, diverse cohort of US children and adolescents. The Bone
Mineral Density in Childhood study was a mixed longitudinal study with 7393
observations on 1743 subjects. Annually, we measured BMC by dual-energy X-ray
absorptiometry (DXA), physical activity and calcium intake by questionnaire, and
pubertal development (Tanner stage) by examination for up to 7 years. Mixed
effects regression models were used to assess physical activity and calcium
intake effects on BMC accrual at each Tanner stage. We found that self-reported
weight-bearing physical activity contributed to significantly greater BMC accrual
in both sexes and racial subgroups (black and nonblack). In nonblack males, the
magnitude of the activity effect on total body BMC accrual varied among Tanner
stages after adjustment for calcium intake; the greatest difference between high-
and low-activity boys was in Tanner stage 3. Calcium intake had a significant
effect on bone accrual only in nonblack girls. This effect was not significantly
different among Tanner stages. Our findings do not support differential effects
of physical activity or calcium intake on bone mass accrual according to
maturational stage. The study demonstrated significant longitudinal effects of
weight-bearing physical activity on bone mass accrual through all stages of
pubertal development.
PMID- 25130424
TI - Residual left atrial mass after myxoma resection.
PMID- 25130423
TI - Response: Does perioperative dexmedetomidine improve mortality after coronary
artery bypass surgery?
PMID- 25130425
TI - Dynamism of the mitral annulus: a spatial and temporal analysis.
AB - OBJECTIVE: In this study, the authors sought to investigate the extent and timing
of changes in mitral annular area during the cardiac cycle. Particularly, the
authors assessed whether these changes were limited to the posterior part of the
annulus or were more global in nature. DESIGN: Prospective, observational study
SETTING: Tertiary care university hospital PARTICIPANTS: Twenty three patients
undergoing non-valvular cardiac surgery and 3 patients undergoing vascular
procedures. INTERVENTIONS: Intraoperative 3-dimensional transesophageal
echocardiographic data obtained from patients with normal mitral valves
undergoing non-valvular cardiac surgery were analyzed geometrically. Annular
areas and diameters were measured during various stages of the cardiac cycle.
Intertrigonal distance also was measured using 3D data. MEASUREMENTS AND MAIN
RESULTS: Both anterior and posterior portions of the mitral annulus demonstrated
dynamism throughout the cardiac cycle. The expansion phase ranged from mid
systole to early-diastole, whereas mid-diastole to early-systole was
characterized by an annular contraction phase. Area changes were contributed
equally by anterior and posterior parts of the annulus. Annular dimensions
increased in accordance with mitral annular area (p<0.05). Echocardiographically
identified intertrigonal distance showed the least delta change. CONCLUSIONS:
Both the anterior and posterior parts of the annulus contribute to changes in
mitral annular area, which undergoes discrete expansion and contraction phases
that extend into both systole and diastole. Compared to other annular dimensions,
the echocardiographically-identified intertrigonal distance does not change
significantly during the cardiac cycle.
PMID- 25130426
TI - Does perioperative dexmedetomidine improve mortality after coronary artery bypass
surgery?
PMID- 25130427
TI - Genetic ablation of solute carrier family 7a3a leads to hepatic steatosis in
zebrafish during fasting.
AB - Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver
disorder caused by abnormal lipid metabolisms, such as reduced hepatic fatty acid
oxidation (FAO), but intracellular control of FAO under physio- and pathological
conditions remains largely undefined. Here, we demonstrate that deprivation of
Slc7a3a leads to hepatic steatosis in fasted zebrafish as a result of defects in
arginine-dependent nitric oxide (NO) synthesis. Fast-induced hepatic steatosis in
slc7a3a-null mutants can be rescued by treatments with NO donor, cyclic guanosine
monophosphate analog, adenosine-monophosphate-activated protein kinase (AMPK)
activator, or peroxisome proliferator-activated receptor alpha (PPAR-alpha)
agonist. In contrast, inhibitors of NO synthases, AMPK, or soluble guanylate
cyclase and liver-specifically expressed dominant negatives of peroxisome
proliferator-activated receptor-gamma coactivator 1 alpha and PPAR-alpha are
sufficient to induce hepatic steatosis in fasted wild-type larvae. Moreover,
knockdown of Slc7a3 in mice or SLC7A3 in human liver cells impaired AMPK-PPAR
alpha signaling and resulted in lipid accumulation under fasting or glucose
starvation, respectively. CONCLUSION: These findings have revealed a NO-AMPK-PPAR
alpha-signaling pathway that is crucial for the control of hepatic FAO in
vertebrates.
PMID- 25130428
TI - Pressure pain thresholds fluctuate with, but do not usefully predict, the
clinical course of painful temporomandibular disorder.
AB - Central sensitization elicits pain hypersensitivity and is thought to be causally
implicated in painful temporomandibular disorder (TMD). This causal inference is
based on cross-sectional evidence that people with TMD have greater sensitivity
than controls to noxious stimuli. We tested this inference in the Orofacial Pain:
Prospective Evaluation and Risk Assessment (OPPERA) prospective cohort study of
3258 adults with no lifetime history of TMD when enrolled (visit 1). During 5
years of follow-up, 1 group labeled "persistent TMD cases" (n=72) developed first
onset TMD by visit 2 that persisted ? 6 months until visit 3. Another group
labeled "transient TMD cases" (n=75) developed first-onset TMD at visit 2, which
resolved by visit 3. Randomly sampled "controls" (n=126) remained TMD-free
throughout all 3 visits. At each visit, pressure pain thresholds (PPTs) were
measured by algometry at 10 cranial and bodily sites. In persistent TMD case
patients, mean PPTs reduced 43 kPa (P<.0001) between visits 1 and 2 and
thereafter did not change significantly. In transient TMD case patients, mean
PPTs reduced 41 kPa (P<.001) between visits 1 and 2, and then increased 20 kPa
(P<.001) by visit 3. These patterns were similar after excluding cranial sites
symptomatic for TMD. Importantly, visit 1 PPTs had no clinically useful
prognostic value in predicting first-onset TMD (odds ratio [OR]=1.07, P=.15).
Among first-onset case patients, visit 2 PPTs were modest predictors of
persistent TMD (OR=1.36, P=.002). In this longitudinal study, PPTs reduced when
TMD developed then rebounded when TMD resolved. However, premorbid PPTs poorly
predicted TMD incidence, countering the hypothesis that PPTs signify mechanisms
causing first-onset TMD.
PMID- 25130430
TI - Cytokines and disability in interferon-beta-1b treated and untreated women with
multiple sclerosis.
AB - BACKGROUND AND AIMS: T-helper (Th) cells involved in the pathogenesis of multiple
sclerosis (MS) represent a functionally heterogeneous population defined by their
cytokine secretion profile. The effects of immunotherapeutic drugs on the
cytokine network are still not fully clarified. This study aimed to investigate
serum levels of IFN-gamma, TNF-alpha, IL-4, IL-10 in interferon-beta-1b-treated
and untreated women with relapsing-remitting MS (RRMS) in comparison with healthy
controls and the relationship between cytokine concentrations and the degree of
disability. METHODS: The study included 35 women with RRMS and 35 age-matched
healthy controls. The patients were divided in two groups: Group A-without
disease modifying treatment; Group B-treated with interferon-beta-1b. Degree of
disability was assessed by the Expanded Disability Status Scale (EDSS). Serum
cytokine concentrations were measured by ELISA during relapse and remission.
RESULTS: Group A showed higher IFN-gamma in remission (p = 0.0239) than the
controls; Group B had lower IFN-gamma during relapse (p = 0.0226) than controls.
EDSS in relapse correlated with the levels of IL-10 for Group A (p = 0.015) and
with the concentration of IFN-gamma for Group B (p = 0.039). Nontreated patients
showed higher EDSS in relapse compared to the interferon-beta-1b-treated group (p
= 0.005). CONCLUSIONS: We found an imbalance in the patients' cytokine profile,
which may be seen as supportive of the hypothesis that demyelination in the
central nervous system is mediated by Th1 lymphocytes. IFN-gamma is probably one
of the important indicators for intensity of the immune reaction and shows
promise as a potential biomarker for the therapeutic effect of interferon-beta
1b. The role of IL-10 in the autoimmune process needs further investigation.
PMID- 25130431
TI - The effects of Gremlin1 on human umbilical cord blood hematopoietic progenitors.
AB - Bone morphogenetic proteins (BMPs) support malignant hematopoiesis in CML.
Conversely, the multi-functional BMP antagonist Gremlin1 supports self-renewing
cancer stem cells of other malignancies. Inhibition of BMP signaling in CML, or
of Gremlin1 in solid tumors, may therefore have therapeutic potential. However,
since BMPs regulate hematopoietic stem cell (HSC) decisions in the stem cell
niche, it is necessary to determine how Gremlin1 influences normal HSC. We
examined the effects of Gremlin1 on long-term culture-initiating cells (LTC-IC)
and transplantable hematopoietic stem cells (SCID-repopulating cells: SRC) in
human umbilical cord blood. Gremlin1 inhibited BMP signaling, downregulated BMP-6
and cyclin E2 expression and upregulated hairy and enhancer of split-1 (HES-1; a
Notch transcriptional target) and Hedgehog interacting protein-1 (HHIP-1; an
inhibitor of Hedgehog signaling). The functional effects of Gremlin1 on SRC, i.e.
skewing of their myelopoietic:lymphopoietic potential towards B lymphopoiesis
without affecting long-term engraftment potential, were entirely consistent with
changes in gene expression induced by Gremlin1. Since both BMPs and Gremlin1 are
secreted by osteoblasts in vivo, our studies provide potential insights into the
molecular regulation of hematopoiesis in the stem cell niche. These results also
suggest that Gremlin1 (and possibly its mimetics that may be developed for
therapeutic use) may not adversely affect normal human hematopoietic stem cell
survival, though they may reduce their myelopoietic potential.
PMID- 25130429
TI - Natural antioxidants exhibit chemopreventive characteristics through the
regulation of CNC b-Zip transcription factors in estrogen-induced breast
carcinogenesis.
AB - The objective of the present study was to characterize the role of resveratrol
(Res) and vitamin C (VC) in prevention of estrogen-induced breast cancer through
regulation of cap "n"collar (CNC) b-zip transcription factors. Human breast
epithelial cell line MCF-10A was treated with 17beta-estradiol (E2) and VC or Res
with or without E2. mRNA and protein expression levels of CNC b-zip transcription
factors nuclear factor erythroid 2-related factor 1 (Nrf1), nuclear factor
erythroid 2 related factor 2 (Nrf2), nuclear factor erythroid 2 related factor 3
(Nrf3), and Nrf2-regulated antioxidant enzymes superoxide dismutase 3 (SOD3) and
NAD(P)H: quinone oxidoreductase 1 (NQO1) were quantified. The treatment with E2
suppressed, whereas VC and Res prevented E2-mediated decrease in the expression
levels of SOD3, NQO1, Nrf2 mRNA, and protein in MCF-10A cells. The treatment with
E2, Res, or VC significantly increased mRNA and protein expression levels of
Nrf1. 17beta-Estradiol treatment significantly increased but VC or Res decreased
Nrf3 mRNA and protein expression levels. Our studies demonstrate that estrogen
induced breast cancer might be prevented through upregulation of antioxidant
enzymes via Nrf-dependent pathways.
PMID- 25130432
TI - Cellular proteolytic modification of tumor-suppressor CYLD is critical for the
initiation of human T-cell acute lymphoblastic leukemia.
AB - There exists a general recognition of the fact that post translational
modification of CYLD protein through proteolytic cleavage by MALT-1 results in
sustained cellular NF-kB activity which is conspicuously found to be associated
with cancer in general and hematological malignancies in particular. The present
study was directed to understand the contribution of MALT-1 and deubiquitinase
CYLD to the initiation of T-cell acute lymphoblastic leukemia (T-ALL). Such a
study revealed for the first time that the 35kDa CYLD cleaved factor generated by
MALT-1 mediated proteolytic cleavage was conspicuously present in human T- ALL
subjects of pediatric age group. Further, over-expression of this 35kDa CYLD
factor within normal human peripheral blood mononuclear cells had the inherent
capacity to program the genome of these cells resulting in T-cell lineage ALL.
Based upon these results, we propose that MALT1 inhibitors may be of crucial
importance in the treatment of T-ALL subjects of pediatric age group.
PMID- 25130433
TI - IFN-gamma CA microsatellite polymorphism is associated with susceptibility to
respiratory syncytial virus Infection and severity.
AB - AIM: IFN-gamma, an essential cytokine in the viral cell-mediated immune response,
has been associated with the pathogenesis of respiratory syncytial virus (RSV)
bronchiolitis and to the severity of the infection. The aim of this study was to
investigate whether IFN-gamma CA microsatellite (rs3138557) polymorphism was
associated with susceptibility to RSV in Chinese Han children and with the
severity of the infection. METHODS: The IFN-gamma CA microsatellite was tested in
218 RSV bronchiolitis inpatients and 303 healthy controls, and the severity of
the RSV bronchiolitis was evaluated using a standardised respiratory scoring
system. RESULTS: The frequencies of CA12+/CA12+, CA12+/CA12- and CA12-/CA12- in
the 218 RSV bronchiolitis patients and 303 controls were approximately 11% versus
19%, 55% versus 53% and 34% versus 28%, respectively. The gene polymorphism of
IFN-gamma CA repeats between the two groups was statistically different. The
clinical respiratory scores of RSV bronchiolitis cases with CA12+/CA12+ and
CA12+/CA12- were 2.84 +/- 0.40 (SD) and 2.95 +/- 0.44 (SD), respectively, and
these were significantly lower than the 3.1 +/- 0.36 (SD) score for those with
CA12-/CA12-. CONCLUSION: IFN-gamma CA microsatellite polymorphism was associated
with the susceptibility of Chinese Han children to RSV and the severity of the
infection.
PMID- 25130434
TI - Photocatalytic CO2 conversion over alkali modified TiO2 without loading noble
metal cocatalyst.
AB - Surface modification of TiO2 with NaOH promoted the chemisorption, activation and
photocatalytic CO2 reduction. An optimized loading amount of NaOH kept a good
balance between CO2 chemisorption quantity and BET surface area of TiO2. This
noble metal free method provides a simple pathway for effective multiple H(+)/e(
) CO2 photoreduction.
PMID- 25130435
TI - Phylogeny suggests nondirectional and isometric evolution of sexual size
dimorphism in argiopine spiders.
AB - Sexual dimorphism describes substantial differences between male and female
phenotypes. In spiders, sexual dimorphism research almost exclusively focuses on
size, and recent studies have recovered steady evolutionary size increases in
females, and independent evolutionary size changes in males. Their discordance is
due to negative allometric size patterns caused by different selection pressures
on male and female sizes (converse Rensch's rule). Here, we investigated
macroevolutionary patterns of sexual size dimorphism (SSD) in Argiopinae, a
global lineage of orb-weaving spiders with varying degrees of SSD. We devised a
Bayesian and maximum-likelihood molecular species-level phylogeny, and then used
it to reconstruct sex-specific size evolution, to examine general hypotheses and
different models of size evolution, to test for sexual size coevolution, and to
examine allometric patterns of SSD. Our results, revealing ancestral moderate
sizes and SSD, failed to reject the Brownian motion model, which suggests a
nondirectional size evolution. Contrary to predictions, male and female sizes
were phylogenetically correlated, and SSD evolution was isometric. We interpret
these results to question the classical explanations of female-biased SSD via
fecundity, gravity, and differential mortality. In argiopines, SSD evolution may
be driven by these or additional selection mechanisms, but perhaps at different
phylogenetic scales.
PMID- 25130436
TI - In search of the "Holy Grail": will we ever prove the efficacy of Rapid Response
Systems (RRS)?
PMID- 25130437
TI - Non-coding RNAs: a novel level of genome complexity.
PMID- 25130438
TI - Lumisterol is metabolized by CYP11A1: discovery of a new pathway.
AB - Lumisterol3 (L3) is produced by photochemical transformation of 7
dehydrocholesterol (7-DHC) during exposure to high doses of ultraviolet B
radiation. It has been assumed that L3 is biologically inactive and is not
metabolized in the body. However, some synthetic derivatives of L3 display
biological activity. The aim of this study was to test the ability of CYP11A1 to
metabolize L3. Incubation of L3 with bovine or human CYP11A1 resulted in the
formation of three major and a number of minor products. The catalytic efficiency
of bovine CYP11A1 for metabolism of L3 dissolved in 2-hydroxypropyl-beta
cyclodextrin was approximately 20% of that reported for vitamin D3 and
cholesterol. The structures of the three major products were identified as 24
hydroxy-L3, 22-hydroxy-L3 and 20,22-dihydroxy-L3 by NMR. 22-Hydroxy-L3 was
further metabolized by bovine CYP11A1 to 20,22-dihydroxy-L3. Both 22-hydroxy-L3
and 20,22-dihydroxy-L3 gave rise to a minor metabolite identified from authentic
standard and mass spectrometry as pregnalumisterol (pL) (product of C20-C22 side
chain cleavage of L3) and two trihydroxy-L3 products. The capability of tissues
expressing CYP11A1 to metabolize L3 was demonstrated using pig adrenal fragments
where 20,22-dihydroxy-L3, 22-hydroxy-L3, 24-hydroxy-L3 and pL were detected by
LC/MS. Thus, we have established that L3 is metabolized by CYP11A1 to 22- and 24
hydroxy-L3 and 20,22-dihydroxy-L3 as major products, as well as to pL and other
minor products. The previously reported biological activity of pL and the
presence of CYP11A1 in skin suggest that this pathway may serve to produce
biologically active products from L3, emphasizing a novel role of CYP11A1 in
sterol metabolism.
PMID- 25130439
TI - Endotoxin-induced vascular endothelial cell migration is dependent on TLR4/NF
kappaB pathway, NAD(P)H oxidase activation, and transient receptor potential
melastatin 7 calcium channel activity.
AB - Endothelial dysfunction is decisive and leads to the development of several
inflammatory diseases. Endotoxemia-derived sepsis syndrome exhibits a broad
inflammation-induced endothelial dysfunction. We reported previously that the
endotoxin, lipopolysaccharide (LPS), induces the conversion of endothelial cells
(ECs) into activated fibroblasts, showing a myofibroblast-like protein expression
profile. Enhanced migration is a hallmark of myofibroblast function. However, the
mechanism involved in LPS-induced EC migration is no totally understood. Some
studies have shown that the transient receptor potential melastatin 7 (TRPM7) ion
channel is involved in fibroblast and tumor cell migration through the regulation
of calcium influx. Furthermore, LPS modulates TRPM7 expression. However, whether
TRPM7 is involved in LPS-induced EC migration remains unknown. Here, we study the
participation of LPS as an inducer of EC migration and study the mechanism
underlying evaluating the participation of the TRPM7 ion channel. Our results
demonstrate that LPS induced EC migration in a dose-dependent manner.
Furthermore, this migratory process was mediated by the TLR-4/NF-kappaB pathway
and the generation of ROS through the PKC-activated NAD(P)H oxidase. In addition,
LPS increased the intracellular calcium level and the number of focal adhesion
kinase (FAK)-positive focal adhesions in EC. Finally, we demonstrate that using
TRPM7 blockers or suppressing TRPM7 expression through siRNA successfully
inhibits the calcium influx and the LPS-induced EC migration. These results point
out TRPM7 as a new target in the drug design for several inflammatory diseases
that impair vascular endothelium function.
PMID- 25130441
TI - Lack of association of LOXL1 gene variants in Japanese patients with central
retinal vein occlusion without clinically detectable pseudoexfoliation material
deposits.
AB - PURPOSE: A possible association has been reported between exfoliation syndrome
(EX) and various ocular and systemic vascular disorders; however, it is unclear
if there is an association between EX and central retinal vein occlusion (CRVO).
Because latent deposits of exfoliation materials might not be recognized during
slit-lamp examination, an ocular biopsy is required to establish a precise
diagnosis. We evaluated a possible association between EX and CRVO using lysyl
oxidase-like 1 (LOXL1) gene variants as alternative markers for EX. METHODS: The
allelic and genotypic frequencies of three LOXL1 variants (rs1048661, rs3825942,
and rs2165241) were determined in 68 consecutive Japanese patients with CRVO [15
with exfoliation syndrome (EX+) and 53 without exfoliation syndrome (EX-)] and 90
control patients with cataract without EX (CT). RESULTS: The frequencies of the
rs1048661 and rs3825942 variants showed borderline difference between the CRVO
and CT groups (p = 0.04085 and p = 0.06088, respectively, for allelic
frequencies, and p = 0.06838 and p = 0.03482, respectively, for genotypic
frequencies). Compared with the CT group, subgroup analysis showed that the CRVO
EX+ group had significant differences in the allelic and genotypic frequencies of
rs1048661 (p = 0.0006447 and p = 0.0001392, respectively) and had borderline
differences in the allelic and genotypic frequencies of rs3825942 (p = 0.03403
and p = 0.07341, respectively), while the CRVO EX- group did not (p = 0.1324
0.6306). Subgroup analysis showed that the frequencies of rs2165241 did not
differ between the CRVO and CT groups. CONCLUSIONS: When the LOXL1 variants were
used as disease markers for clinically undetectable EX, there was no association
between CRVO and EX. The results suggested that the LOXL1 variants, which are
well-established markers for EX, are not likely genetic markers for CRVO in
Japanese subjects.
PMID- 25130440
TI - Mouse monocyte chemoattractant protein 1 (MCP1) functions as a monomer.
AB - Monocyte chemoattractant protein 1 (MCP1) is an important chemoattractant for
microglia. Rodent MCP1 carries a heavily glycosylated C-terminus, which has been
predicted to increase local MCP1 concentration, promote MCP1
dimerization/oligomerization, and facilitate receptor engagement. Previous
studies have shown that MCP1 mutant lacking the glycosylated C-terminus cannot
dimerize/oligomerize, but has higher chemotactic potency than the wild-type (full
length) MCP1, suggesting that rodent MCP1 may function as a monomer. Although
many groups support this hypothesis, there is no direct evidence on whether
rodent MCP1 dimer is functional. In this paper, using forced recombinant dimeric
MCP1 proteins we show that mouse MCP1 dimer is unable to activate Rac1, promote
protrusion of lamellipodia, or induce microglial migration, although it can bind
to CCR2 and mediate its internalization. These results support the idea that
signaling events mediated by MCP1 require the presence of the monomeric form of
this chemokine.
PMID- 25130442
TI - How resistant is 'treatment-resistant' obsessive-compulsive disorder in youth?
AB - OBJECTIVES: Obsessive-compulsive disorder (OCD) is often perceived as being
difficult to treat. This study aimed to test the hypothesis that treatment non
response in routine clinical practice is often due to failures in the delivery of
treatment, and that most patients who are apparently treatment-resistant will
respond to treatment if adequately delivered. DESIGN: Retrospective cohort data
analysis. METHODS: Forty-three young people with severe, treatment-resistant OCD
(defined as Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS] scores >=
30 and non-response to previous cognitive behaviour therapy [CBT] and selective
serotonin reuptake inhibitors) were referred to a specialist clinic and completed
a course of manualized CBT, with (N = 21) or without (N = 22) optimization of
medication. A sub-sample (N = 15) completed a semi-structured interview to
determine characteristics of their previous CBT; quality was assessed according
to pre-determined criteria. RESULTS: Specialist treatment was associated with
significant reductions in OCD symptoms at post-treatment with gains maintained at
3-month follow-up. At the 3-month follow-up, 58% of patients showed a meaningful
clinical response (>= 35% drop on the CY-BOCS) and 22% were in remission (<= 12
on the CY-BOCS). Patients whose medication was optimized tended (non
significantly) to have better responses. The quality of previous CBT was assessed
in a sub-group of participants and rated as inadequate in 95.5% of cases. The
most common inadequacy was insufficient focus on exposure techniques.
CONCLUSIONS: These findings provide support for the notion that treatment non
response in routine practice may be due to technical treatment failures and
highlight the need to disseminate good quality evidence-based treatment among
this population. Research is also needed to understand factors that impede
outcome to further improve response and remission rates. PRACTITIONER POINTS:
Among young people with OCD, failure to respond to treatment in routine clinical
practice may often reflect the nature of the treatment received. Exposure
techniques may often be overlooked in CBT for OCD, potentially resulting in poor
therapeutic response. Most young people with severe and apparent treatment
resistant OCD respond to outpatient CBT incorporating E/RP. Further research is
needed to establish effective methods for disseminating good quality CBT for OCD.
PMID- 25130443
TI - Preliminary characterisation of nanotubes connecting T-cells and their use by HIV
1.
AB - BACKGROUND INFORMATION: Cells, especially those of the immune system, can form
long and thin connections termed tunnelling nanotubes (TNTs). These structures
can reach >100 um in length and, in T-cells, contain actin but no tubulin and are
not open ended. T-cell TNTs were found to form following cell contact and to
enable the transfer of HIV-1 from an infected- to a connected-T-cell. TNTs are
poorly characterised at molecular level. RESULTS: We found Rab11 and
tetraspanins, especially CD81, all along T-cells TNTs, whereas Rab4 and Rab35
were absent from these structures. Regarding actin cytoskeleton regulators,
Exo70, N-WASP and especially ezrin accumulated at the level of the TNT tip that
contacts the connected cell. Phosphoinositides such as PI(4,5)P2 were also
concentrated at this level together with HIV-1 Gag. Gag spots on cells and TNTs
were essentially immobile, and likely correspond to area of Gag multimerisation
for budding to form virus-like particles. Mobility of PHPLCdelta , a specific
probe for PI(4,5)P2 , was reduced > threefold at the level of TNT basis or tip
compared with the cell body. CONCLUSION: Our study identified the TNT tip as an
active zone of actin cytoskeleton reorganisation with the presence of ezrin,
Exo70, N-WASP and PI(4,5)P2 . The latter is also known to enable HIV-1 Gag
recruitment for viral budding, and the presence of Gag at this level, contacting
the connected cell, indicates that the TNT tip is also a favourite place for HIV
1 assembly and budding.
PMID- 25130445
TI - Improved tracking performance of Lagrangian block-matching methodologies using
block expansion in the time domain: in silico, phantom and in vivo evaluations.
AB - The aim of this study was to evaluate tracking performance when an extra
reference block is added to a basic block-matching method, where the two
reference blocks originate from two consecutive ultrasound frames. The use of an
extra reference block was evaluated for two putative benefits: (i) an increase in
tracking performance while maintaining the size of the reference blocks,
evaluated using in silico and phantom cine loops; (ii) a reduction in the size of
the reference blocks while maintaining the tracking performance, evaluated using
in vivo cine loops of the common carotid artery where the longitudinal movement
of the wall was estimated. The results indicated that tracking accuracy improved
(mean = 48%, p < 0.005 [in silico]; mean = 43%, p < 0.01 [phantom]), and there
was a reduction in size of the reference blocks while maintaining tracking
performance (mean = 19%, p < 0.01 [in vivo]). This novel method will facilitate
further exploration of the longitudinal movement of the arterial wall.
PMID- 25130444
TI - Comparison of strain and shear wave elastography for the differentiation of
benign from malignant breast lesions, combined with B-mode ultrasonography:
qualitative and quantitative assessments.
AB - Our aim was to compare the diagnostic performance of strain elastography (SE) and
shear-wave elastography (SWE), combined with B-mode ultrasonography (US), in
breast cancer. For 79 breast lesions that underwent SE and SWE, two radiologists
reviewed five data sets (B-mode US, SWE, SE and two combined sets). Qualitative
and quantitative elastographic data and Breast Imaging Reporting and Data System
(BI-RADS) categories were recorded. The area under the receiver operating
characteristic curve (AUC) was evaluated. No significant difference in the AUC
between the two elastography methods was noted. After subjective assessment by
reviewers, the AUC for the combined sets was improved (SWE, 0.987; SE, 0.982; B
mode US, 0.970; p < 0.05). When SE and SWE were added, 38% and 56% of benign BI
RADS category 4a lesions with a low suspicion of cancer were downgraded without
false-negative results, respectively. SE and SWE performed similarly. Therefore,
addition of SE or SWE improved the diagnostic performance of B-mode US,
potentially reducing unnecessary biopsies.
PMID- 25130447
TI - Computation of the temperature rise at the corneal endothelium during cataract
surgery by modeling of heat generation inside the anterior chamber.
AB - The corneal endothelium sustaining the transparency of the cornea is a vulnerable
cell layer. Thermal exposure during phacoemulsification is considered to be a
potential cause of post-operative cell loss. Knowledge of the temperature rise
and particularly of its dependence on region and system settings could deliver
useful information about a potential correlation with cell damage. However, there
exists a lack of understanding of the process and location of heat generation.
Analytical calculations and experiments enabled the quantification of different
mechanisms acting as heat sources during phacoemulsification. Heat generation
caused by viscous friction was estimated using both an analytical approach and a
numerical simulation. In contrast to absorption of sound and self-heating of the
probe, this effect was ascertained to be the main heat source. Calorimetric
measurement of the power input verified this modeling. On the basis of these
results, the local temperature distribution inside a porcine eye was computed
time dependently using the finite-element method. Two different amplitude
settings were compared with respect to the temperature increase at the corneal
endothelium. Various conclusions on the mitigation of thermal exposure during
treatment can be drawn from this finite-element simulation.
PMID- 25130446
TI - Monitoring and staging abdominal aortic aneurysm disease with pulse wave imaging.
AB - The abdominal aortic aneurysm (AAA) is a silent and often deadly vascular disease
caused by the localized weakening of the arterial wall. Previous work has
indicated that local changes in wall stiffness can be detected with pulse wave
imaging (PWI), which is a non-invasive technique for tracking the propagation of
pulse waves along the aorta at high spatial and temporal resolutions. The aim of
this study was to assess the capability of PWI to monitor and stage AAA
progression in a murine model of the disease. ApoE/TIMP-1 knockout mice (N = 18)
were given angiotensin II for 30 days via subcutaneously implanted osmotic pumps.
The suprarenal sections of the abdominal aortas were imaged every 2-3 d after
implantation using a 30-MHz VisualSonics Vevo 770 with 15-MUm lateral resolution.
Pulse wave propagation was monitored at an effective frame rate of 8 kHz by using
retrospective electrocardiogram gating and by performing 1-D cross-correlation on
the radiofrequency signals to obtain the displacements induced by the waves. In
normal aortas, the pulse waves propagated at constant velocities (2.8 +/- 0.9
m/s, r(2) = 0.89 +/- 0.11), indicating that the composition of these vessels was
relatively homogeneous. In the mice that developed AAAs (N = 10), the wave speeds
in the aneurysm sac were 45% lower (1.6 +/- 0.6 m/s) and were more variable (r(2)
= 0.66 +/- 0.23). Moreover, the wave-induced wall displacements were at least 80%
lower within the sacs compared with the surrounding vessel. Finally, in mice that
developed fissures (N = 5) or ruptures (N = 3) at the sites of their AAA, higher
displacements directed out of the lumen and with no discernible wave pattern
(r(2) < 0.20) were observed throughout the cardiac cycle. These findings indicate
that PWI can be used to distinguish normal murine aortas from aneurysmal,
fissured and ruptured ones. Hence, PWI could potentially be used to monitor and
stage human aneurysms by providing information complementary to standard B-mode
ultrasound.
PMID- 25130448
TI - A new method for measuring the speed of sound in rat liver ex vivo using an
ultrasound system: correlation of sound speed with fat deposition.
AB - The speed of sound correlates well with the fat content of the liver. Therefore,
non-invasive quantification of sound speed in the liver might be of diagnostic
value. Here we describe a new non-invasive method that would be clinically
applicable for measurement of sound speed in the liver. Sprague-Dawley rats were
divided into two groups: a control group and a fatty liver group prepared by
keeping the rats on a choline-deficient diet for 6 wk. The livers were subjected
to pathologic and biochemical analysis; the speed of sound through the liver
tissue was measured using our proposed method and a pulser-receiver as standard.
Our results indicated that use of the proposed method makes it feasible to
diagnose fatty liver with good accuracy on the basis of sound speed. This
approach would have considerable potential for non-invasive diagnosis of fatty
liver and would be a valuable adjunct to conventional liver diagnostic
procedures.
PMID- 25130449
TI - Localized in vivo model drug delivery with intravascular ultrasound and
microbubbles.
AB - An intravascular ultrasound (IVUS) and microbubble drug delivery system was
evaluated in both ex vivo and in vivo swine vessel models. Microbubbles with the
fluorophore DiI embedded in the shell as a model drug were infused into ex vivo
swine arteries at a physiologic flow rate (105 mL/min) while a 5-MHz IVUS
transducer applied ultrasound. Ultrasound pulse sequences consisted of acoustic
radiation force pulses to displace DiI-loaded microbubbles from the vessel lumen
to the wall, followed by higher-intensity delivery pulses to release DiI into the
vessel wall. Insonation with both the acoustic radiation force pulse and the
delivery pulse increased DiI deposition 10-fold compared with deposition with the
delivery pulse alone. Localized delivery of DiI was then demonstrated in an in
vivo swine model. The theoretical transducer beam width predicted the measured
angular extent of delivery to within 11%. These results indicate that low
frequency IVUS catheters are a viable method for achieving localized drug
delivery with microbubbles.
PMID- 25130450
TI - Teles-operated echocardiography using a robotic arm and an internet connection.
AB - The objective was to design and validate a method of tele-operated
echocardiography. The method was tested in a hospital facility with an expert
sonographer located in a room 10 m away from the patient. An ultrasound probe,
fixed to a motorized probe holder, was located on the patient by a non
sonographer and was remotely controlled by the expert sonographer via an Internet
connection. Scans were performed on 41 cardiac patients. The quality of the
cardiac views obtained using tele-echocardiography was lower than that of
reference echocardiography, but generated similar measurements in 93%-100% of the
cases. Bland-Altman plots and statistical comparison of tele- and reference
echocardiography measures revealed no differences (p > 0.05). Of the 71 valve
leaks or aortic stenoses present, 61 (86%) were detected using tele
echocardiography. These results indicate that tele-echocardiography provided
reliable diagnoses and acceptable measurements in 86% and 93% of cases,
respectively, with no false-positive diagnoses being reported.
PMID- 25130451
TI - High-intensity focused ultrasound leads to histopathologic changes of the
inferior turbinate mucosa with allergic inflammation.
AB - This study was aimed at understanding the histopathologic changes that occur in
the nasal mucosa of patients with perennial allergic rhinitis after high
intensity focused ultrasound (HIFU) treatment. Biopsy specimens of the inferior
turbinate mucosa were taken from 11 PAR patients before, immediately after and 1
y after HIFU treatment. Morphometric analysis revealed that the density of
eosinophils and other inflammatory cells increased immediately after treatment
and then were decreased significantly 1 y post-treatment. Submucosal glands were
swollen and venous sinusoids were dilated, but there was no statistically
significant change in their density, immediately after treatment. However, both
glands and venous sinusoids significantly decreased in number 1 y after HIFU
treatment. The ciliated epithelium or basement membrane of the nasal mucosa was
well preserved at all stages. In conclusion, HIFU is a tolerable and effective
treatment to reduce inflammation of the inferior turbinate mucosa in patients
with perennial allergic rhinitis.
PMID- 25130452
TI - Reliability of automatic vibratory equipment for ultrasonic strain measurement of
the median nerve.
AB - The objective of this study was to test the reliability of ultrasonic median
nerve strain measurements using automatic vibratory equipment. Strain ratios of
the median nerve in the carpal tunnel model and the reference coupler were
measured at three different settings of the transducer: 0, +2 and +4 mm (+ =
compressing the model down 2-4 mm initially). After measurement of the carpal
tunnel model, a +4-mm setting was chosen for in vivo measurement. The median
nerve strains of 30 wrists were measured by two examiners using the equipment.
Intra- and inter-examiner correlation coefficients (CCs) for the strain ratios
were calculated. The closest ratio was found in the +4-mm placement (strain
ratio: 0.73, Young's modulus ratio: 0.79). The intra-examiner CC was 0.91 (p <
0.01), and the inter-examiner CCs were 0.72-0.78 (p < 0.01). The automatic
vibratory equipment was useful in quantifying median nerve strain at the wrist.
PMID- 25130453
TI - Is the frequent sonographic anechoic area distally in metacarpophalangeal joints
a sign of arthritis?
AB - In clinical practice, ultrasonography (US) often reveals, in the dorsal scan, a
small anechoic area distally in both inflamed and clinically non-inflamed
metacarpophalangeal joints. This "distal anechogenicity in the
metacarpophalangeal joint" (DAEM) might thus be scored false positively as
arthritis. We aimed to investigate whether the DAEM is a sign of arthritis. We
evaluated the prevalence of DAEMs in 24 non-arthritic subjects. We then compared
the dimensions of the DAEM in 10 non-arthritic subjects with a DAEM and 7
consecutive rheumatoid arthritis (RA) outpatients, using 2-D and 3-D ultrasound.
Furthermore, we dissected two fresh-frozen postmortem hand specimens after US. A
DAEM was observed in the metacarpophalangeal 2 (MCP2) joints of 54% of the 24 non
selected non-arthritic individuals; in none of those did the joint exhibit a
power Doppler signal. A DAEM was observed in 86% of the 7 RA patients. Dimensions
of DAEMs did not statistically significantly differ between these groups. At 3-D
imaging and dissection, the DAEM was found to be an extension of the
metacarpophalangeal joint capsule. In conclusion, DAEMs occur frequently and are
not a sign of arthritis, but are distal joint recesses. This should be taken into
account when using current sensitive ultrasonographic scoring systems grading
arthritis.
PMID- 25130454
TI - A new metric for measuring condition in large predatory sharks.
AB - A simple metric (span condition analysis; SCA) is presented for quantifying the
condition of sharks based on four measurements of body girth relative to body
length. Data on 104 live sharks from four species that vary in body form,
behaviour and habitat use (Carcharhinus leucas, Carcharhinus limbatus,
Ginglymostoma cirratum and Galeocerdo cuvier) are given. Condition shows similar
levels of variability among individuals within each species. Carcharhinus leucas
showed a positive relationship between condition and body size, whereas the other
three species showed no relationship. There was little evidence for strong
differences in condition between males and females, although more male sharks are
needed for some species (e.g. G. cuvier) to verify this finding. SCA is
potentially viable for other large marine or terrestrial animals that are
captured live and then released.
PMID- 25130455
TI - Friends interventions in psychosis: a narrative review and call to action.
AB - AIMS: To highlight the importance of friendships to young people with psychosis,
and the need for clinical interventions to help maintain peer relationships
during illness. To structure a research agenda for developing evidence-based
interventions with friends. METHOD: An argument is developed through a narrative
review of (i) the proven efficacy of family interventions, and (by comparison) a
relative absence of friend-based interventions; (ii) the particular primacy of
friendships and dating for young people, and typical effects of exclusion; and
(iii) reduced friendship networks and dating experiences in psychosis, in pre-,
during and post-psychosis phases, also links between exclusion and psychosis.
RESULTS: We put forward a model of how poor friendships can potentially be a
causal and/or maintenance factor for psychotic symptoms. Given this model, our
thesis is that interventions aiming to maintain social networks can be hugely
beneficial clinically for young people with psychosis. We give a case study to
show how such an intervention can work. CONCLUSIONS: We call for 'friends
interventions' for young people with psychosis to be developed, where
professionals directly work with a young person's authentic social group to
support key friendships and maintain social continuity. An agenda for future
research is presented that will develop and test theoretically driven
interventions.
PMID- 25130457
TI - Effect of truncated neurokinin-1 receptor expression changes on the interaction
between human breast cancer and bone marrow-derived mesenchymal stem cells.
AB - Previous studies in breast cancer cell lines showed that truncated neurokinin
receptor-1 (NK1R-Tr) was able to promote malignant transformation of breast
cells, and NK1R-Tr may contribute to tumor progression and promote distant
metastasis in human breast cancer. A co-culture model of breast cancer and bone
marrow-derived human mesenchymal stem (HMSC-bm) cells showed that HMSC-bm
inhibited the growth of breast cancer cells and entered the bone marrow at early
stages. Down-regulation of NK1R-Tr may be a key factor in maintaining the
quiescent phenotype of breast cancer cells among bone marrow stroma. Stromal
derived factor (SDF)-1alpha expression was negatively correlated with NK1R-Tr
expression in breast cancer cells. Secretion of SDF-1alpha by HMSC-bm may
maintain the quiescent phenotype of breast cancer cells among bone marrow stroma
by down-regulating NK1R-Tr expression. Transforming growth factor (TGF)-beta1
expression was positively associated with NK1R-Tr expression in breast cancer
cells. In a co-culture system, MDA-MB-231-TGF-beta1I (TGF-beta genes were
suppressed using specific shRNA) cells were able to attach to HMSC-bm quickly,
indicating that TGF-beta1 was also a key factor for maintaining the quiescent
phenotype of breast cancer cells in bone marrow stroma. However, the detailed
mechanism still remained unclear and could involve other molecules, in addition
to NK1R-Tr.
PMID- 25130456
TI - Differential partial activation phenotype and production of tumour necrosis
factor-alpha by conventional dendritic cells in response to lipopolysaccharide in
HIV+ viraemic subjects and HIV+ controllers.
AB - HIV(+) subjects are reported to have increased soluble CD14 (sCD14) in plasma, an
indicator of microbial translocation. We evaluated if microbial translocation has
a differential impact on the activation and function of conventional dendritic
cells (cDC) from viraemic HIV(+) subjects and HIV(+) controllers (CTs). The
HIV(+) subjects were classified into two groups according to their plasma viral
load (pVL): CT and viraemic. Subjects without HIV were included as controls (HIV(
) ). The frequencies and phenotypes of cDC from these subjects were evaluated by
multi-parameter flow cytometry. In addition, peripheral blood mononuclear cells
(PBMCs) were stimulated with lipopolysaccharide (LPS) or single-stranded RNA40
(ssRNA40), the phenotype of the cDC and the intracellular production of tumour
necrosis factor (TNF)-alpha by the cDC were evaluated by flow cytometry. We
observed a partial activation phenotype for the cDC in the viraemic subjects and
CTs ex vivo and after LPS activation, which showed differences in the expression
of CD40 and CD86. Furthermore, in response to LPS the cDC from the viraemic
subjects produced more TNF-alpha compared to the cDC from CTs. Interestingly, the
percentage of TNF-alpha(+) cDC was found to be correlated positively with the
pVL. The partial activation of cDC and the over-production of TNF-alpha in
response to LPS in viraemic HIV(+) subjects might be related to the increased
chronic activation observed in these subjects. In contrast, cDC from CTs seem to
have a regulated response to LPS, indicating that they respond differently to
chronic immune activation. These results may have implications in the development
of HIV therapies and vaccines using DC.
PMID- 25130459
TI - An update on red blood cell storage lesions, as gleaned through biochemistry and
omics technologies.
AB - Red blood cell (RBC) aging in the blood bank is characterized by the accumulation
of a significant number of biochemical and morphologic alterations. Recent mass
spectrometry and electron microscopy studies have provided novel insights into
the molecular changes underpinning the accumulation of storage lesions to RBCs in
the blood bank. Biochemical lesions include altered cation homeostasis,
reprogrammed energy, and redox metabolism, which result in the impairment of
enzymatic activity and progressive depletion of high-energy phosphate compounds.
These factors contribute to the progressive accumulation of oxidative stress,
which in turn promotes oxidative lesions to proteins (carbonylation,
fragmentation, hemoglobin glycation) and lipids (peroxidation). Biochemical
lesions negatively affect RBC morphology, which is marked by progressive membrane
blebbing and vesiculation. These storage lesions contribute to the altered
physiology of long-stored RBCs and promote the rapid clearance of up to one
fourth of long-stored RBCs from the recipient's bloodstream after 24 hours from
administration. While prospective clinical evidence is accumulating, from the
present review it emerges that biochemical, morphologic, and omics profiles of
stored RBCs have observable changes after approximately 14 days of storage.
Future studies will assess whether these in vitro observations might have
clinically meaningful effects.
PMID- 25130460
TI - Cecropin A-melittin mutant with improved proteolytic stability and enhanced
antimicrobial activity against bacteria and fungi associated with gastroenteritis
in vitro.
AB - Cecropin A-melittin (CAM), a chimeric antimicrobial peptide with potent
antimicrobial activity, is threatened by some special extracellular proteases
when used to deal with certain drug-resistant pathogenic microbes in the
gastrointestinal tract. Thus, a four-tryptophan-substitution mutant (CAM-W) from
CAM was developed via the replacement of special amino acid residues to enhance
the antimicrobial potency and to improve the proteolytic stability of this agent.
The pharmaceutical index of CAM-W was investigated, with a focus on biological
potency, cytotoxicity, and proteolytic stability, as well as pH and thermal
resistance. CAM-W exhibited potent antimicrobial activity and was approximately 3
12 times higher than that of CAM. CAM-W also exhibited a strong antifungal
activity against a series of common pathogenic fungi, in a lower IC50 range
between 2.1mg/L and 3.3mg/L than that of its reference CAM ranging from 9.8mg/L
to 14.2mg/L. Besides, CAM-W showed moderate cytotoxicity (IC50>300mg/L) in
erythrocyte lysis test. In addition, CAM-W overcame challenges under various
conditions, including specific temperatures (20, 30, 40, 50, 60, 70, 80, and 90
degrees C), pH values (2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, and 9.0), and proteases
(trypsin, pepsin, human neutrophil elastase, Pseudomonas aeruginosa elastase, and
Staphylococcus aureus V8 protease) that are commonly present in human
gastrointestinal tract. These results suggest that the four-tryptophan
substitution can confer CAM-W with a high pharmaceutical index, which is
important for CAM-W to become a potential alternative to conventional antibiotics
against bacteria and fungi associated with gastroenteritis.
PMID- 25130458
TI - Sex-specific behavioral traits in the Brd2 mouse model of juvenile myoclonic
epilepsy.
AB - Idiopathic generalized epilepsy represents about 30-35% of all epilepsies in
humans. The bromodomain BRD2 gene has been repeatedly associated with the
subsyndrome of juvenile myoclonic epilepsy (JME). Our previous work determined
that mice haploinsufficient in Brd2 (Brd2+/-) have increased susceptibility to
provoked seizures, develop spontaneous seizures and have significantly decreased
gamma-aminobutyric acid (GABA) markers in the direct basal ganglia pathway as
well as in the neocortex and superior colliculus. Here, we tested male and female
Brd2+/- and wild-type littermate mice in a battery of behavioral tests (open
field, tube dominance test, elevated plus maze, Morris water maze and Barnes
maze) to identify whether Brd2 haploinsufficiency is associated with the human
behavioral patterns, the so-called JME personality. Brd2+/- females but not males
consistently displayed decreased anxiety. Furthermore, we found a highly
significant dominance trait (aggression) in the Brd2+/- mice compared with the
wild type, more pronounced in females. Brd2+/- mice of either sex did not differ
from wild-type mice in spatial learning and memory tests. Compared with wild-type
littermates, we found decreased numbers of GABA neurons in the basolateral
amygdala, which is consistent with the increase in aggressive behavior. Our
results indicate that Brd2+/- haploinsufficient mice show no cognitive impairment
but have behavioral traits similar to those found in patients with JME
(recklessness, aggression). This suggests that either the BRD2 gene is directly
responsible for influencing many traits of JME or it controls upstream regulators
of individual phenotypes.
PMID- 25130461
TI - Cholesterol efflux from THP-1 macrophages is impaired by the fatty acid component
from lipoprotein hydrolysis by lipoprotein lipase.
AB - Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes
triglycerides within circulating lipoproteins. Macrophage LPL contributes to
atherogenesis, but the mechanisms behind it are poorly understood. We
hypothesized that the products of lipoprotein hydrolysis generated by LPL promote
atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To
test this hypothesis, we treated human THP-1 macrophages with total lipoproteins
that were hydrolyzed by LPL and we found significantly reduced transcript levels
for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1),
ABCG1, and scavenger receptor BI. These decreases were likely due to significant
reductions for the nuclear receptors liver-X-receptor-alpha, peroxisome
proliferator activated receptor (PPAR)-alpha, and PPAR-gamma. We prepared a
mixture of free fatty acids (FFA) that represented the ratios of FFA species
within lipoprotein hydrolysis products, and we found that the FFA mixture also
significantly reduced cholesterol transporters and nuclear receptors. Finally, we
tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I,
and we found that the treatment of THP-1 macrophages with the FFA mixture
significantly attenuated cholesterol efflux. Overall, these data show that the
FFA component of lipoprotein hydrolysis products generated by LPL may promote
atherogenesis by inhibiting cholesterol efflux, which partially explains the pro
atherogenic role of macrophage LPL.
PMID- 25130462
TI - Testosterone treatment increases androgen receptor and aromatase gene expression
in myotubes from patients with PCOS and controls, but does not induce insulin
resistance.
AB - Polycystic ovary syndrome (PCOS) is associated with insulin resistance and
increased risk of type 2 diabetes. Skeletal muscle is the major site of insulin
mediated glucose disposal and the skeletal muscle tissue is capable to
synthesize, convert and degrade androgens. Insulin sensitivity is conserved in
cultured myotubes (in vitro) from patients with PCOS, but the effect of
testosterone on this insulin sensitivity is unknown. We investigated the effect
of 7days testosterone treatment (100nmol/l) on glucose transport and gene
expression levels of hormone receptors and enzymes involved in the synthesis and
conversion of testosterone (HSD17B1, HSD17B2, CYP19A1, SRD5A1-2, AR, ER-alpha,
HSD17B6 and AKR1-3) in myotubes from ten patients with PCOS and ten matched
controls. Testosterone treatment significantly increased aromatase and androgen
receptor gene expression levels in patients and controls. Glucose transport in
myotubes was comparable in patients with PCOS vs. controls and was unchanged by
testosterone treatment (p=0.21 PCOS vs. controls). These results suggest that
testosterone treatment of myotubes increases the aromatase and androgen receptor
gene expression without affecting insulin sensitivity and if testosterone is
implicated in muscular insulin resistance in PCOS, this is by and indirect
mechanism.
PMID- 25130463
TI - PDI family protein ERp29 forms 1:1 complex with lectin chaperone calreticulin.
AB - Lectin chaperone calreticulin is well known to interact with ERp57 which is one
of PDI family proteins. The interaction of ERp57 with calreticulin is believed to
assist disulfide bond formation of nascent glycoprotein in the ER. Various kinds
of PDI family proteins are present in the ER, however, their precise roles have
been unclear. In this study, interaction assay between PDI family proteins and
calreticulin by SPR analysis was performed. Our analysis revealed for the first
time formation of a 1:1 complex between ERp29 and calreticulin. The dissociation
constant of interaction between ERp29 and calreticulin was shown to be almost
identical to ERp57-calreticulin interaction. We speculate that the recognition
site of ERp29 within calreticulin is different from that of ERp57.
PMID- 25130464
TI - Leucine methylation of protein phosphatase PP4C at C-terminal is critical for its
cellular functions.
AB - BACKGROUND: Protein phosphatase 4 (PP4) has been known to have critical functions
in DNA double strand break (DSB) repair and cell cycle by the regulation of
phosphorylation of its target proteins, such as H2AX, RPA2, KAP-1, 53BP1.
However, it is largely unknown how PP4 itself is regulated. METHODS: We examined
the PP4C methylation on L307 at C-terminal by using methylated-leucine specific
antibody. Then with PP4C L307A mutant, we explored that how nonmethylated form of
PP4C affects its known cellular functions by immunoprecipitation,
immunofluorescence, and DNA DSB repair assays. RESULTS: Here we show that PP4C is
methylated on its C-terminal leucine residue in vivo and this methylation is
important for cellular functions mediated by PP4. In the cells PP4C L307A mutant
has significantly low activity of dephosphorylation against its known target
proteins, and the loss of interaction between L307A PP4 mutant and regulatory
subunits, R1, R2, or R3alpha/beta causes the dissociation from its target
proteins. Moreover, PP4C L307A mutant loses its role in both DSB repair pathways,
HR (homologous recombination) and NHEJ (non-homologous end joining), which
phenocopies PP4C depletion. CONCLUSION: Our results demonstrate the key site of
PP4C methylation and establish the physiological importance of this regulation.
PMID- 25130465
TI - Differential impact of glucose levels and advanced glycation end-products on
tubular cell viability and pro-inflammatory/profibrotic functions.
AB - High glucose (HG) or synthetic advanced glycation end-products (AGE) conditions
are generally used to mimic diabetes in cellular models. Both models have shown
an increase of apoptosis, oxidative stress and pro-inflammatory cytokine
production in tubular cells. However, the impact of the two conditions combined
has rarely been studied. In addition, the impact of glucose level variation due
to cellular consumption is not clearly characterized in such experiments.
Therefore, the aim of this study was to compare the effect of HG and AGE
separately and of both on tubular cell phenotype changes in the HK2 cell line.
Moreover, glucose consumption was monitored every hour to maintain the glucose
level by supplementation throughout the experiments. We thus observed a
significant decrease of apoptosis and H2O2 production in the HK2 cell. HG or AGE
treatment induced an increase of total and mitochondrial apoptosis as well as TGF
beta release compared to control conditions; however, AGE or HG led to apoptosis
preferentially involving the mitochondria pathway. No cumulative effect of HG and
AGE treatment was observed on apoptosis. However, a pretreatment with RAGE
antibodies partially abolished the apoptotic effect of HG and completely
abolished the apoptotic effect of AGE. In conclusion, tubular cells are sensitive
to the lack of glucose as well as to the HG and AGE treatments, the AGE effect
being more deleterious than the HG effect. Absence of a potential synergistic
effect of HG and AGE could indicate that they act through a common pathway,
possibly via the activation of the RAGE receptors.
PMID- 25130466
TI - LOX-1 - dependent mitochondrial DNA damage and NLRP3 activation during systemic
inflammation in mice.
AB - BACKGROUND: Lectin-like oxidized low-density lipoprotein scavenger receptor-1
(LOX-1) is known to be involved in many pathophysiological events, such as
inflammation. METHODS: To clarify the role of LOX-1 in mtDNA damage and NLRP3
inflammasome activation, we studied wild-type (WT) and LOX-1 knockout (KO) mice
given thioglycollate, an inflammatory stimulus. RESULTS: We observed intense
inflammatory response (CD45 and CD68 expression) and mtDNA damage in spleen and
kidneys of WT mice given thioglycollate. The abrogation of LOX-1 (use of LOX-1
knockout mice) reduced the inflammatory response as well as mtDNA damage (P<0.05
vs. WT mice). We also observed that mice with LOX-1 deletion had markedly reduced
expression of caspase-1 (P10 and P20 subunits) as well as cleaved IL-1beta and IL
18. These mice also had much less mtDNA damage and only limited NLRP3
inflammasome expression. CONCLUSIONS: These in vivo observations indicate that
LOX-1 plays a key role in mtDNA damage which then leads to NLRP3 inflammasome
activation during inflammation.
PMID- 25130468
TI - Biophysical and biological meanings of healthspan from C. elegans cohort.
AB - Lifespan among individuals ranges widely in organisms from yeast to mammals, even
in an isogenic cohort born in a nearly uniform environment. Needless to say,
genetic and environmental factors are essential for aging and lifespan, but in
addition, a third factor or the existence of a stochastic element must be
reflected in aging and lifespan. An essential point is that lifespan or aging is
an unpredictable phenomenon. The present study focuses on elucidating the
biophysical and biological meanings of healthspan that latently indwells a
stochastic nature. To perform this purpose, the nematode Caenorhabditis elegans
served as a model animal. C. elegans fed a healthy food had an extended
healthspan as compared to those fed a conventional diet. Then, utilizing this
phenomenon, we clarified a mechanism of healthspan extension by measuring the
single-worm ATP and estimating the ATP noise (or the variability of the ATP
content) among individual worms and by quantitatively analyzing biodemographic
data with the lifespan equation that was derived from a fluctuation theory.
PMID- 25130467
TI - Chemical rescue of DeltaF508-CFTR in C127 epithelial cells reverses aberrant
extracellular pH acidification to wild-type alkalization as monitored by
microphysiometry.
AB - Cystic fibrosis (CF) is caused by mutations in the gene for CFTR, a cAMP
activated anion channel expressed in apical membranes of wet epithelia. Since
CFTR is permeable to HCO3(-), and may regulate bicarbonate exchangers, it is not
surprising evidence of changes in extracellular pH (pHo) have been found in CF.
Previously we have shown that tracking pHo can be used to differentiate cells
expressing wild-type CFTR from controls in mouse mammary epithelial (C127) and
fibroblast (NIH/3T3) cell lines. In this study we characterized forskolin
stimulated extracellular acidification rates in epithelia where chemical
correction of mutant DeltaF508-CFTR converted an aberrant response in
acidification (10%+ increase) to wild-type (25%+ decrease). Thus treatment with
corrector (10% glycerol) and the resulting increased expression of DeltaF508-CFTR
at the surface was detected by microphysiometry as a significant reversal from
acidification to alkalization of pHo. These results suggest that CFTR activation
as well as correction can be detected by carefully monitoring pHo and support
findings in the field that extracellular pH acidification may impact the function
of airway surface liquid in CF.
PMID- 25130469
TI - NFkappaB activation is essential for miR-21 induction by TGFbeta1 in high glucose
conditions.
AB - Transforming growth factor beta1 (TGFbeta1) is a pleiotropic growth factor with a
very broad spectrum of effects on wound healing. Chronic non-healing wounds such
as diabetic foot ulcers express reduced levels of TGFbeta1. On the other hand,
our previous studies have shown that the microRNA miR-21 is differentially
regulated in diabetic wounds and that it promotes migration of fibroblast cells.
Although interplay between TGFbeta1 and miR-21 are studied in relation to cancer,
their interaction in the context of chronic wounds has not yet been investigated.
In this study, we examined if TGFbeta1 could stimulate miR-21 in fibroblasts that
are subjected to high glucose environment. MiR-21 was, in fact, induced by
TGFbeta1 in high glucose conditions. The induction by TGFbeta1 was dependent on
NFkappaB activation and subsequent ROS generation. TGFbeta1 was instrumental in
degrading the NFkappaB inhibitor IkappaBalpha and facilitating the nuclear
translocation of NFkappaB p65 subunit. EMSA studies showed enhanced DNA binding
activity of NFkappaB in the presence of TGFbeta1. ChIP assay revealed binding of
p65 to miR-21 promoter. NFkappaB activation was also required for the nuclear
translocation of Smad 4 protein and subsequent direct interaction of Smad
proteins with primary miR-21 as revealed by RNA-IP studies. Our results show that
manipulation of TGFbeta1-NFkappaB-miR-21 pathway could serve as an innovative
approach towards therapeutics to heal diabetic ulcers.
PMID- 25130470
TI - Fasting times in serum PSA assay.
PMID- 25130471
TI - Prospects for clinically relevant epigenetic tests in the andrology laboratory.
PMID- 25130472
TI - Risk prediction models for biochemical recurrence after radical prostatectomy
using prostate-specific antigen and Gleason score.
AB - Many computer models for predicting the risk of prostate cancer have been
developed including for prediction of biochemical recurrence (BCR). However,
models for individual BCR free probability at individual time-points after a BCR
free period are rare. Follow-up data from 1656 patients who underwent
laparoscopic radical prostatectomy (LRP) were used to develop an artificial
neural network (ANN) to predict BCR and to compare it with a logistic regression
(LR) model using clinical and pathologic parameters, prostate-specific antigen
(PSA), margin status (R0/1), pathological stage (pT), and Gleason Score (GS). For
individual BCR prediction at any given time after operation, additional ANN, and
LR models were calculated every 6 months for up to 7.5 years of follow-up. The
areas under the receiver operating characteristic (ROC) curve (AUC) for the ANN
(0.754) and LR models (0.755) calculated immediately following LRP, were larger
than that for GS (AUC: 0.715; P = 0.0015 and 0.001), pT or PSA (AUC: 0.619; P
always <0.0001) alone. The GS predicted the BCR better than PSA (P = 0.0001), but
there was no difference between the ANN and LR models (P = 0.39). Our ANN and LR
models predicted individual BCR risk from radical prostatectomy for up to 10
years postoperative. ANN and LR models equally and significantly improved the
prediction of BCR compared with PSA and GS alone. When the GS and ANN output
values are combined, a more accurate BCR prediction is possible, especially in
high-risk patients with GS >=7.
PMID- 25130474
TI - Hiccups and gastroesophageal reflux disease as seen on high resolution esophageal
manometry.
PMID- 25130473
TI - Correlates of adolescent and young adult sexual initiation patterns.
AB - CONTEXT: Identifying adolescent characteristics associated with different
patterns of sexual initiation is critical to promoting healthy sexual
development. METHODS: Patterns of sexual initiation were examined among 12,378
respondents to Waves 1 (1994-1995) and 4 (2008) of the National Longitudinal
Study of Adolescent Health. Multinomial logistic regression explored associations
between adolescent characteristics and membership in five latent classes
capturing the timing, sequence, pace and variety of sexual initiation patterns.
RESULTS: Age and indicators of greater psychosocial conventionality were
associated with membership in the atypical "postponers" class (characterized by
postponement of oral, vaginal and anal sexual activity until early adulthood),
although patterns of associations varied by gender. For example, compared with
males who attended religious services at least once a week, males who never
attended religious services were more likely to appear in the vaginal
initiators/multiple behaviors class (characterized by initiation of vaginal sex
first and then initiation of another behavior after at least one year), rather
than in the postponers class (relative risk ratio, 2.5). Compared with women who
prayed at least once a day, those who never prayed were more likely to be in the
vaginal initiators/single behavior class (whose members typically engaged in only
one type of behavior), rather than in the postponers class (2.0). CONCLUSIONS:
Individuals who are more adherent, and presumably more committed, to the
attitudes, values and expectations of conventional society are more likely than
others to delay multiple types of sexual activity until well beyond the norm for
their peers.
PMID- 25130475
TI - Validation of mechanical, electrical and thermal nociceptive stimulation methods
in horses.
AB - REASONS FOR PERFORMING STUDY: To validate a model for investigating the effects
of analgesic drugs on mechanical, thermal and electrical stimulation testing.
OBJECTIVES: To investigate repeatability, sensitivity and specificity of
nociceptive tests. STUDY DESIGN: Randomised experiment with 2 observers in 2
phases. METHODS: Mechanical (M), thermal (TL) and electrical (E) stimuli were
applied to the dorsal metacarpus (M-left and TL-right) and coronary band of the
left thoracic limb (E) and a thoracic thermal stimulus (TT) was applied caudal to
the withers in 8 horses (405 +/- 43 kg). Stimuli intensities were increased until
a clear avoidance response was detected without exceeding 20 N (M), 60 degrees C
(TL and TT) and 15 V (E). For each set of tests, 3 real stimuli and one sham
stimulus were applied (32 per animal) using a blinded, randomised, crossover
design repeated after 6 months. A distribution frequency and, for each stimulus,
Chi-square and McNemar tests compared both the proportion of positive responses
detected by 2 observers and the 2 study phases. The kappa coefficients estimated
interobserver agreement in determining endpoints. Sensitivity (384 tests) and
specificity (128 tests) were evaluated for each nociceptive stimulus to assess
the evaluators' accuracy in detecting real and sham stimuli. RESULTS: Nociceptive
thresholds were 3.1 +/- 2 N (M), 8.1 +/- 3.8 V (E), 51.4 +/- 5.5 degrees C (TL)
and 55.2 +/- 5.3 degrees C (TT). The level of agreement after all tests, M, E, TL
and TT, was 90, 100, 84, 98 and 75%, respectively. Sensitivity was 89, 100, 89,
98 and 70% and specificity 92, 97, 88, 91 and 94%, respectively. CONCLUSIONS: The
high interobserver agreement, sensitivity and specificity suggest that M, E and
TL tests are valid for pain studies in horses and are suitable tools for
investigating antinociceptive effects of analgesics in horses.
PMID- 25130476
TI - Sequential ofatumumab and lenalidomide for the treatment of relapsed and
refractory chronic lymphocytic leukemia and small lymphocytic lymphoma.
AB - Ofatumumab is a fully human anti-CD20 monoclonal antibody with enhanced antibody
dependent and complement dependent cytotoxicity. Lenalidomide induces T cell and
natural killer (NK) cell activation and in vitro enhances clearance of chronic
lymphocytic leukemia (CLL) cells by monoclonal antibodies. We performed a multi
center, phase 2 trial of sequential treatment with ofatumumab and lenalidomide in
patients with advanced, relapsed and refractory (R/R) CLL, consisting of
ofatumumab 2000 mg intravenously on day 1 and lenalidomide 10 mg on days 8-28,
for up to six cycles. Twenty-one subjects were included with median age of 63
years and two prior lines of therapy. The overall response rate was 47.6% and
23.8% had stable disease. Median overall survival was 21.5 months. Neutropenia
and thrombocytopenia were the most frequent adverse events. Tumor flare reaction
occurred in 43% of subjects. Intracycle sequential ofatumumab plus lenalidomide
is active in high-risk R/R CLL and well tolerated except for frequent cytopenias.
PMID- 25130477
TI - Activating somatic mutations in diffuse large B-cell lymphomas: lessons from next
generation sequencing and key elements in the precision medicine era.
AB - Diffuse large B-cell lymphoma (DLBCL) is the most common form of lymphoma,
accounting for 30-40% of newly diagnosed non-Hodgkin lymphomas. Historically,
DLBCL has been thought to involve recurrent translocations of the immunoglobulin
heavy (IGH) locus and the deregulation of rearranged oncogenes. Whole exome
sequencing (WES) of more than 200 DLBCLs has completely redefined the genetic
landscape of the disease by identifying recurrent single nucleotide variants and
providing new therapeutic opportunities in DLBCL molecular subtypes. Some of
these somatic mutations target genes that play a crucial role in B-cell function
(B cell receptor [BCR] signaling, nuclear factor kappaB [NF-kappaB] pathway, Toll
like receptor [TLR] signaling and phosphatidylinositol 3-kinase [PI3K] pathway),
immunity, cell cycle/apoptosis or chromatin modification. In this review,
following an overview of the somatic mutations reported in DLBCL, we focus on
activating and clustered mutations targeting genes including MYD88, CD79A/B, EZH2
and CARD11 and discuss their clinical and therapeutic relevance in the precision
medicine era.
PMID- 25130480
TI - Interface control of the magnetic chirality in CoFeB/MgO heterostructures with
heavy-metal underlayers.
AB - Recent advances in the understanding of spin orbital effects in ultrathin
magnetic heterostructures have opened new paradigms to control magnetic moments
electrically. The Dzyaloshinskii-Moriya interaction (DMI) is said to play a key
role in forming a Neel-type domain wall that can be driven by the spin Hall
torque. Here we show that the strength and sign of the DMI can be changed by
modifying the adjacent heavy-metal underlayer (X) in perpendicularly magnetized
X/CoFeB/MgO heterostructures. The sense of rotation of a domain wall spiral is
reversed when the underlayer is changed from Hf, Ta to W and the strength of DMI
varies as the filling of 5d orbitals, or the electronegativity, of the heavy
metal layer changes. The DMI can even be tuned by adding nitrogen to the
underlayer, thus allowing interface engineering of the magnetic texture in
ultrathin magnetic heterostructures.
PMID- 25130479
TI - Estradiol induces gene proximity and MLL-MLLT3 fusion in an activation-induced
cytidine deaminase-mediated pathway.
AB - Epidemiological data have linked birth control formulations to an increased risk
of infant acute leukemia involving MLL rearrangements. Reverse transcription
polymerase chain reaction (RT-PCR) studies showed that 10 nM estradiol enhanced
MLL transcription in addition to its common translocation partners, MLLT2 (AF4)
and MLLT3 (AF9). The same concentration of estradiol triggered MLL and MLLT3 co
localization without affecting the interaction of genes located on the same
chromosomes. Estradiol also stimulated the generation of MLL-MLLT3 fusion
transcripts as seen by RT-PCR. RNAi knockdown of activation-induced cytidine
deaminase (AICDA) suppressed the induction of MLL-MLLT3 fusion transcript
formation observed with estradiol. Additionally, chromatin immunoprecipitation
(ChIP) analysis showed estradiol dependent localization of AICDA in MLL intron
11, upstream of a hotspot for both DNA cleavage and rearrangement, but not
downstream within intron 12. Combined, these studies show that levels of
estradiol consistent with that observed during pregnancy have the potential to
initiate MLL fusions through an AICDA-mediated mechanism.
PMID- 25130478
TI - Assessment of carbonic anhydrase IX expression and extracellular pH in B-cell
lymphoma cell line models.
AB - The expression of carbonic anhydrase IX (CA IX) and its relationship to acidosis
in lymphomas has not been widely studied. We investigated the protein expression
of CA IX in a human B-cell lymphoma tissue microarray, and in Raji, Ramos and
Granta 519 lymphoma cell lines and tumor models, while also investigating the
relationship with hypoxia. An imaging method, acidoCEST magnetic resonance
imaging (MRI), was used to estimate lymphoma xenograft extracellular pH (pHe).
Our results showed that clinical lymphoma tissues and cell line models in vitro
and in vivo had moderate CA IX expression. Although in vitro studies showed that
CA IX expression was induced by hypoxia, in vivo studies did not show this
correlation. Untreated lymphoma xenograft tumor pHe had acidic fractions, and an
acidity score was qualitatively correlated with CA IX expression. Therefore, CA
IX is expressed in B-cell lymphomas and is qualitatively correlated with
extracellular acidosis in xenograft tumor models.
PMID- 25130481
TI - Aqueous route to facile, efficient and functional silica coating of metal
nanoparticles at room temperature.
AB - Various metal (Ag, Au, and Pt)@thiol-functionalized silica (SiO2-SH)
nanoparticles (NPs) are successfully prepared at room temperature by a facile,
efficient, functional, universal and scalable coating process in alcohol-free
aqueous solution using pre-hydrolyzed 3-(mercaptopropyl)trimethoxysilane (MPTMS).
The controlled pre-hydrolysis of the silane precursor in water and the
consecutive condensation processes are the key to achieve the effective and
uniform silica coating on metal NPs in aqueous solution. The thickness of the
silica shell is tuned by simply varying the coating time. The silica shell can
act as an effective protecting layer for Ag NPs in Ag@SiO2-SH NPs under
conditions for silica coating in aqueous solution; however, it leads to a
directional dissolution of Ag NPs in a more strongly basic ammonia solution. The
environmentally friendly silica coating process in water is also applied to
prepare highly surface-enhanced Raman scattering (SERS)-active Ag@SiO2-SH NPs
with different types of Raman molecules for highly sensitive SERS-based
applications in various fields.
PMID- 25130482
TI - Spectroscopic analysis of catalytic water oxidation by [Ru(II)(bpy)(tpy)H2O]2+
suggests that Ru(V)?O is not a rate-limiting intermediate.
AB - Modern chemistry's grand challenge is to significantly improve catalysts for
water splitting. Further progress requires detailed spectroscopic and
computational characterization of catalytic mechanisms. We analyzed one of the
most studied homogeneous single-site Ru catalysts, [Ru(II)(bpy)(tpy)H2O](2+)
(where bpy = 2,2'-bipyridine, tpy = 2,2';6',2"-terpyridine). Our results reveal
that the [Ru(V)(bpy)(tpy)?O](3+) intermediate, reportedly detected in catalytic
mixtures as a rate-limiting intermediate in water activation, is not present as
such. Using a combination of electron paramagnetic resonance (EPR) and X-ray
absorption spectroscopy, we demonstrate that 95% of the Ru complex in the
catalytic steady state is of the form [Ru(IV)(bpy)(tpy)?O](2+).
[Ru(V)(bpy)(tpy)?O](3+) was not observed, and according to density functional
theory (DFT) analysis, it might be thermodynamically inaccessible at our
experimental conditions. A reaction product with unique EPR spectrum was detected
in reaction mixtures at about 5% and assigned to Ru(III)-peroxo species with (
OOH or -OO- ligands). We also analyzed the [Ru(II)(bpy)(tpy)Cl](+) catalyst
precursor and confirmed that this molecule is not a catalyst and its oxidation
past Ru(III) state is impeded by a lack of proton-coupled electron transfer. Ru
Cl exchange with water is required to form active catalysts with the Ru-H2O
fragment. [Ru(II)(bpy)(tpy)H2O](2+) is the simplest representative of a larger
class of water oxidation catalysts with neutral, nitrogen containing
heterocycles. We expect this class of catalysts to work mechanistically in a
similar fashion via [Ru(IV)(bpy)(tpy)?O](2+) intermediate unless more
electronegative (oxygen containing) ligands are introduced in the Ru coordination
sphere, allowing the formation of more oxidized Ru(V) intermediate.
PMID- 25130483
TI - The Mirror Program: Preparing Women for the Postoperative Mastectomy Mirror
Viewing Experience.
AB - PROBLEM: Preparing women for the experiences they will endure during the breast
cancer trajectory improves psychological outcomes and quality of life. Women have
found that it may be difficult to view themselves in a mirror after having a
mastectomy. Supporting women who have had a mastectomy in mirror-viewing and body
image is a relatively new yet important intervention in oncology nursing.
METHODS: The feasibility of a preoperative mirror program given by oncology nurse
navigators to women who were scheduled for a mastectomy was examined in this
randomized control study. FINDINGS: Pre- and postoperative data on anxiety, body
image, depression, emotional well-being, and mirror use were collected from
intervention participants (n = 10) and control subjects (n = 9). CONCLUSION: This
article illustrates the development of the mirror program and the results of the
feasibility trial, and provides a discussion with implications for future
research.
PMID- 25130484
TI - Let-7a is differentially expressed in bronchial biopsies of patients with severe
asthma.
AB - Asthma is a chronic inflammatory disease. Around 5 to 10% of patients classified
as having severe asthma can-not be adequately controlled despite the use of all
currently available therapeutic approaches. Previous studies have revealed the
potential important role of miRNAs in the regulation of a variety of inflammatory
processes, including asthma. Expression of selected miRNAs, specifically let-7a,
miR-21 and miR-223, that were shown to have important roles in asthma
pathogenesis, were analyzed in bronchial biopsies of 24 patients with asthma, 12
mild and 12 severe, and 10 controls with no chronic disease. We found
significantly reduced expression of let-7a in bronchial biopsies from patients
with severe asthma in comparison to patients with mild asthma as well as in
comparison to the non-asthmatic controls. On the other hand, no significant
differences in miR-21 and miR-223 expression were found between the different
groups analyzed. Reduced let-7a levels in bronchial biopsies of patients with
severe therapy-resistant asthma could not only be used as a potential biomarker
to discriminate between different asthma phenotypes, but also might be a target
for modulation of treatment at the inflammatory site for a group of patients that
are most affected and still lack effective treatment.
PMID- 25130485
TI - Interfacial molecular restructuring of plasticized polymers in water.
AB - Upon water contact, phthalate-plasticized poly(vinyl chloride) (PVC) surfaces are
highly unstable because the plasticizer molecules are not covalently bound to the
polymer network. As a result, it is difficult to predict how the surface polymer
chains and plasticizers may interact with water without directly probing the
plastic/water interface in situ. We successfully studied the molecular surface
restructuring of 10 wt% and 25 wt% bis 2-ethylhexyl phthalate (DEHP)-plasticized
and pure PVC films (deposited on solid substrates) in situ due to water contact
using sum frequency generation (SFG) vibrational spectroscopy. SFG spectral
signals from both the top and the bottom of the plastic film were obtained
simultaneously, so a thin-film model spectral analysis was applied to separately
identify the molecular changes of plastics at the surface and the
plastic/substrate interface in water. It was found that in water both the
structures of the plastic surface and the buried plastic/substrate interface
changed. After removing the samples from the water and exposing them to air
again, the surface structures did not completely recover. Further SFG experiments
confirmed that small amounts of DEHP were transferred into the water. The leached
DEHP molecules could reorder and permanently transfer to new surfaces through
water contact. Our studies indicate that small amounts of phthalates can transfer
from surface to surface through water contact in an overall scope of minutes.
This study yields vital new information on the molecular surface structures of
DEHP plasticized PVC in water, and the transfer behaviors and environmental fate
of plasticizers in polymers.
PMID- 25130486
TI - Effect of LEPR, ABCG2 and SCD1 gene polymorphisms on reproductive traits in the
Iranian Holstein cattle.
AB - During the last decades, genetic selection for milk production traits has led to
increased fertility and health problems in dairy cattle. The aim of this study
was to investigate the impact of three polymorphisms located in the ATP-binding
cassette superfamily G member 2 transporter (ABCG2), stearoyl-CoA desaturase 1
(SCD1) and leptin receptor (LEPR) genes on reproductive traits and somatic cell
count (SCC). The analysis was conducted on 408 randomly selected cows. The SNPs
within the genes (LEPR, ABCG2 and SCD1) were genotyped using the PCR-RFLP method.
All three possible genotypes were observed for SCD1-T878C and LEPR-T945M SNPs,
but not for ABCG2-Y581S SNP. LEPR-T945M and ABCG2-Y581S SNPs had no statistically
significant effect on the studied reproductive traits and SCC. However, SCD1
T878C SNP were negatively and significantly related to pregnancy length, dry days
and open days (p < 0.05), which lead to decreased profitability in dairy herds.
The results suggest that the T878C SNP of SCD1 might be useful as a DNA marker to
decrease reproductive problems and improve production traits in Iranian Holstein
dairy cows.
PMID- 25130487
TI - Identifying predictors of hospital readmission following congenital heart surgery
through analysis of a multiinstitutional administrative Database.
AB - BACKGROUND: Despite resource burdens associated with hospital readmission, there
remains little multiinstitutional data available to identify children at risk for
readmission following congenital heart surgery. METHODS AND RESULTS: Children
undergoing congenital heart surgery and discharged home between January of 2011
and December 2012 were identified within the Pediatric Health Information System
database, a multiinstitutional collection of clinical and administrative data.
Patient discharges were assigned to derivation and validation cohorts for the
purposes of predictive model design, with 17 871 discharges meeting inclusion
criteria. Readmission within 30 days was noted following 956 (11%) of discharges
within the derivation cohort (n = 9104), with a median time to readmission of 9
days (interquartile range [IQR] 5-18 days). Readmissions resulted in a
rehospitalization length of stay of 4 days (IQR 2-8 days) and were associated
with an intensive care unit (ICU) admission in 36% of cases. Independent
perioperative predictors of readmission included Risk Adjustment in Congenital
Heart Surgery score of 6 (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.8
3.7, P < .001) and ICU length of stay of at least 7 days (OR 1.9 95% CI 1.6-2.2,
P < .001). Demographic predictors included Hispanic ethnicity (OR 1.2, 95% CI 1.1
1.4, P = .014) and government payor status (OR 1.2, 95% CI 1.1-1.4, P = .007).
Predictive model performance was modest among validation cohort (c statistic
0.68, 95% CI 0.66-0.69, P < .001). CONCLUSIONS: Readmissions following congenital
heart surgery are common and associated with significant resource consumption.
While we describe independent predictors that may identify patients at risk for
readmission prior to hospital discharge, there likely remains other unreported
factors that may contribute to readmission following congenital heart surgery.
PMID- 25130488
TI - A prognosis based classification of undifferentiated uterine sarcomas:
identification of mitotic index, hormone receptors and YWHAE-FAM22 translocation
status as predictors of survival.
AB - Undifferentiated uterine sarcomas (UUS) are rare tumors with a heterologous
biology and a poor prognosis. The goal of this study was to examine
clinicopathology, biomarkers and YWHAE-FAM22 translocation status, in the
prognosis of these tumors. Twenty-six cases of UUS were included. All original
slides were rereviewed and age at diagnosis, tumor stage, "Kurihara" diagnosis,
mitotic index, presence of necrosis and grade of nuclear atypia were recorded.
Additionally, a tissue microarray was constructed from 22 of the cases, and the
protein biomarkers P53, P16, Ki-67, Cyclin-D1, ER, PR and ANLN were evaluated by
immunohistochemistry. All tumors were evaluated for the presence of a YWHAE-FAM
translocation; the translocation was demonstrated in the three Cyclin-D1 positive
tumors. Follow-up data in the form of overall survival were available on all
patients. These tumors could be divided into two prognostic groups, a high
mitotic index group (10 cases, M = 36.8, SD = 5.4) and a low mitotic index group
(16 cases, M = 8.7, SD = 5.8). These two groups showed a statistically
significant difference in prognosis. The expression of ER, PR or presence of the
YWHAE-FAM22 translocation correlated with low mitotic index and an additionally
improved prognosis, although the number of cases was small. These results
indicate that UUS can be divided into two prognostic groups using mitotic index
as a primary criteria, followed by expression of either ER, PR or the presence of
a YWHAE-FAM22 translocation as a secondary criteria. This study demonstrates the
presence of statistically significant prognostic subgroups within UUS, and
provides treatment insights.
PMID- 25130490
TI - Electron confurcation in anaerobic lactate oxidation.
PMID- 25130489
TI - Characterizing methyl-bearing side chain contacts and dynamics mediating amyloid
beta protofibril interactions using 13C(methyl)-DEST and lifetime line
broadening.
AB - Many details pertaining to the formation and interactions of protein aggregates
associated with neurodegenerative diseases are invisible to conventional
biophysical techniques. We recently introduced (15)N dark-state exchange
saturation transfer (DEST) and (15)N lifetime line-broadening to study solution
backbone dynamics and position-specific binding probabilities for amyloid beta
(Abeta) monomers in exchange with large (2-80 MDa) protofibrillar Abeta
aggregates. Here we use (13)C(methyl)DEST and lifetime line-broadening to probe
the interactions and dynamics of methyl-bearing side chains in the Abeta
protofibril-bound state. We show that all methyl groups of Abeta40 populate
direct-contact bound states with a very fast effective transverse relaxation
rate, indicative of side-chain-mediated direct binding to the protofibril
surface. The data are consistent with position-specific enhancements of
(13)C(methyl)-R2(tethered) values in tethered states, providing further insights
into the structural ensemble of the protofibril-bound state.
PMID- 25130491
TI - Dnmt3a and Dnmt3b have overlapping and distinct functions in hematopoietic stem
cells.
AB - Epigenetic regulation of hematopoietic stem cells (HSCs) ensures lifelong
production of blood and bone marrow. Recently, we reported that loss of de novo
DNA methyltransferase Dnmt3a results in HSC expansion and impaired
differentiation. Here, we report conditional inactivation of Dnmt3b in HSCs
either alone or combined with Dnmt3a deletion. Combined loss of Dnmt3a and Dnmt3b
was synergistic, resulting in enhanced HSC self-renewal and a more severe block
in differentiation than in Dnmt3a-null cells, whereas loss of Dnmt3b resulted in
a mild phenotype. Although the predominant Dnmt3b isoform in adult HSCs is
catalytically inactive, its residual activity in Dnmt3a-null HSCs can drive some
differentiation and generates paradoxical hypermethylation of CpG islands.
Dnmt3a/Dnmt3b-null HSCs displayed activated beta-catenin signaling, partly
accounting for the differentiation block. These data demonstrate distinct roles
for Dnmt3b in HSC differentiation and provide insights into complementary de novo
methylation patterns governing regulation of HSC fate decisions.
PMID- 25130493
TI - Individual patient data from registrational trials of silodosin in the treatment
of non-neurogenic male lower urinary tract symptoms (LUTS) associated with benign
prostatic hyperplasia (BPH): subgroup analyses of efficacy and safety data.
AB - OBJECTIVE: To evaluate efficacy and safety of silodosin in a pooled analysis of
individual patient data from three registrational randomised controlled trials
(RCTs) comparing silodosin and placebo in patients with lower urinary tract
symptoms (LUTS). PATIENTS AND METHODS: A pooled analysis of 1494 patients from
three 12-week, multicentre, double-blind, placebo-controlled phase III RCTs was
performed. Efficacy and safety data were assessed across patients with different
baseline characteristics. RESULTS: Silodosin was significantly more effective
than placebo in improving all International Prostate Symptom Score (IPSS)-related
parameters, and maximum urinary flow rate (Qmax ) regardless of patients age (P <
0.041). Comparing the efficacy of silodosin in the different age groups, there
were no differences for all the IPSS-related parameters, whereas Qmax improvement
was slightly higher in patients aged <65 years (P = 0.009). Silodosin was
significantly more effective than placebo in reducing all IPSS-related parameters
regardless of baseline IPSS (P <= 0.001). Similarly, silodosin was more effective
than placebo in improving IPSS-related parameters regardless of baseline Qmax (P
<= 0.02). Silodosin was associated with significantly higher adverse event (AE)
rates, compared with placebo, in all patient subgroups, with retrograde
ejaculation being the most common. Prevalence of dizziness, orthostatic
hypotension, and discontinuation rate was similar with silodosin and placebo in
most patient subgroups. CONCLUSIONS: We analysed the efficacy and safety of
silodosin in several patient subgroups, showing that silodosin was more effective
than placebo in improving all IPSS-related parameters in all patient subgroups,
whereas AEs were similar. Notably, cardiovascular AEs were not higher in patients
taking antihypertensive drugs or with mild renal function impairment.
Discontinuation rates due to AEs were lower in elderly patients.
PMID- 25130492
TI - Adult hepatocytes are generated by self-duplication rather than stem cell
differentiation.
AB - The liver is thought to utilize facultative stem cells, also known as "oval
cells" or "atypical ductal cells" (ADCs), for regeneration following various
types of injury. However, this notion has been based largely on in vitro studies
and transplantation models; where lineage tracing has been used, results have
been conflicting and effect sizes have been small. Here, we used genetic and
nucleoside analog-based tools to mark and track the origin and contribution of
various cell populations to liver regeneration in vivo following several ADC
inducing insults. We report that, contrary to prevailing stem-cell-based models
of regeneration, virtually all new hepatocytes come from preexisting hepatocytes.
PMID- 25130495
TI - Investigation of pediatric neck response and muscle activation in low-speed
frontal impacts.
AB - Pediatric necks present different responses and injury patterns compared with
those of adults in motor vehicle crashes (MVCs). To evaluate the effect of
different muscle modeling methodologies, three muscle models were developed and
simulated under low-speed frontal impact conditions with an average peak
acceleration of 3g's. The muscle activation curve for the curve-guided model, the
muscle segment was curved using guiding nodes, was further optimized based on
experimental data. The pediatric neck model was also simulated under more severe
frontal impact conditions with an average peak acceleration of 8g's. Simulation
results revealed that the curve-guided model needed more muscle force than the
straight-guided model, in which the muscle segment was straight with guiding
nodes, and the curve-constrained model, in which the muscle segment was curved
without guiding nodes and which imposes more constraints on the head and neck
than the curve-guided model. The predicted head responses for the child finite
element neck model were within or close to the experimental corridors of 3- and 8
g's frontal impacts. The neck injuries for a 10-year-old child commonly occurred
at the interspinous ligament in the C7-T1 segment. The model could be used to
analyze the responses and injuries of pediatric neck and head in low-speed
frontal impacts.
PMID- 25130494
TI - Comparison of therapeutic results from radiofrequency ablation and stereotactic
body radiotherapy in solitary lung tumors measuring 5 cm or smaller.
AB - BACKGROUNDS: This retrospective study was conducted to compare the clinical
outcomes of radiofrequency ablation (RFA) with those of stereotactic body
radiotherapy (SBRT) in patients with lung tumors. METHODS: Local tumor
progression, adverse events, and overall survival were compared in patients who
underwent either RFA or SBRT for a single lung tumor measuring 5 cm or smaller.
This study was approved by the institutional review boards of two institutions.
Informed consent was waived. RESULTS: During September 2009 to June 2012, 48
patients [30 males and 18 females, with a mean age +/- standard deviation (SD) of
75.0 +/- 7.5 years] underwent RFA at one institution and 47 patients (21 males
and 26 females, with a mean age +/- SD of 77.0 +/- 7.5 years) underwent SBRT in
another. The mean maximum tumor diameter +/- SD was 2.0 +/- 0.8 cm (range 0.6-3.9
cm) in the RFA group, and 2.1 +/- 0.9 cm (range 0.8-4.7 cm, p = 0.539) in the
SBRT group. The RFA and SBRT groups showed similar 3-year local tumor progression
[9.6%, 95% confidence interval (CI) 3.6-23.9% vs. 7.0%, 95% CI 0.2-20.2%, p =
0.746] and overall survival rates (86.4%, 95% CI 69.2-94.3% vs. 79.6%, 95% CI
60.6-90.1%, p = 0.738). No factor significantly affected local tumor progression.
A maximum tumor size of 2 cm was identified as a prognostic factor in both
univariate and multivariate analyses. No death was related to treatment
procedures. Major complication rates (Grade 3 adverse events) of the RFA (10.4%,
5/48) and SBRT (8.5%, 4/47, p > 0.999) groups were similar. CONCLUSION: For lung
tumor patients, lung RFA provided local tumor control and survival that were
similar to those achieved using SBRT, with equal safety.
PMID- 25130496
TI - Effectiveness of a stress management program to enhance perimenopausal women's
ability to cope with stress.
AB - AIM: To evaluate the effectiveness of a stress management program to enhance the
ability to cope with stress in perimenopausal women. METHODS: In this quasi
experimental design, a stress management program was provided to an experimental
group (n = 55), while a control group (n = 42) was given an informational
pamphlet. The stress management program included a short lecture, group
discussion, and hands-on training in 2 h sessions once a week for 3 weeks.
Participants were recruited through a public announcement. Data were collected
before and after the intervention, and 1 month following the intervention. The
ability to cope with stress was the primary outcome, while psychological well
being and relief of symptoms were the secondary outcomes. The primary purpose of
this program is to enhance the ability to cope with stress. Therefore, the
aspects of knowledge, coping flexibility, and manageability were measured in the
resultant ability to cope with stress. RESULTS: Compared to the control group,
knowledge in the experimental group improved positively as the primary outcome (P
< 0.01). Changes in coping flexibility were demonstrated within the experimental
group (P < 0.05). A comparison between groups for the secondary outcome of
psychological well-being showed that personal growth (P < 0.05) and happiness (P
< 0.01) significantly improved in the experimental group. In addition, the
secondary outcome of relief of symptoms indicated not improved. CONCLUSION:
Results suggest that the stress management program has the potential to boost
perimenopausal women's ability to cope with stress and improve their
psychological well-being.
PMID- 25130497
TI - Isoform-selective regulation of glycogen phosphorylase by energy deprivation and
phosphorylation in astrocytes.
AB - Glycogen phosphorylase (GP) is activated to degrade glycogen in response to
different stimuli, to support both the astrocyte's own metabolic demand and the
metabolic needs of neurons. The regulatory mechanism allowing such a
glycogenolytic response to distinct triggers remains incompletely understood. In
the present study, we used siRNA-mediated differential knockdown of the two
isoforms of GP expressed in astrocytes, muscle isoform (GPMM), and brain isoform
(GPBB), to analyze isoform-specific regulatory characteristics in a cellular
setting. Subsequently, we tested the response of each isoform to phosphorylation,
triggered by incubation with norepinephrine (NE), and to AMP, increased by
glucose deprivation in cells in which expression of one GP isoform had been
silenced. Successful knockdown was demonstrated on the protein level by Western
blot, and on a functional level by determination of glycogen content showing an
increase in glycogen levels following knockdown of either GPMM or GPBB. NE
triggered glycogenolysis within 15 min in control cells and after GPBB knockdown.
However, astrocytes in which expression of GPMM had been silenced showed a delay
in response to NE, with glycogen levels significantly reduced only after 60 min.
In contrast, allosteric activation of GP by AMP, induced by glucose deprivation,
seemed to mainly affect GPBB, as only knockdown of GPBB, but not of GPMM, delayed
the glycogenolytic response to glucose deprivation. Our results indicate that the
two GP isoforms expressed in astrocytes respond to different physiological
triggers, therefore conferring distinct metabolic functions of brain glycogen.
PMID- 25130498
TI - Robustness to noise of arterial blood flow estimation methods in CT perfusion.
AB - BACKGROUND: Perfusion CT is a technology which allows functional evaluation of
tissue vascularity. Due to this potential, it is finding increasing utility in
oncology. Although since its introduction continuous advances have interested CT
technique, some issues have to be still defined, concerning both clinical and
technical aspects. In this study, we dealt with the comparison of two widely
employed mathematical models (dual input one compartment model - DOCM - and
maximum slope - SM -) analyzing their robustness to the noise. METHODS: We
carried out a computer simulation process to quantify effect of noise on the
evaluation of an important perfusion parameter (Arterial Blood Flow - BFa) in
liver tumours. A total of 4500 liver TAC, corresponding to 3 fixed BFa values,
were simulated using different arterial and portal TAC (computed from 5 real CT
images) at 10 values of signal to noise ratio (SNR). BFa values were calculated
by applying four different algorithms, specifically developed, to these noisy
simulated curves. Three algorithms were developed to implement SM (one
semiautomatic, one automatic and one automatic with filtering) and the last for
the DOCM method. RESULTS: In all the simulations, DOCM provided the best results,
i.e., those with the lowest percentage error compared to the reference value of
BFa. Concerning SM, the results are variable. Results obtained with the automatic
algorithm with filtering are close to the reference value, but only if SNR is
higher than 50. Vice versa, results obtained by means of the semiautomatic
algorithm gave, in all simulations, the lowest results with the lowest standard
deviation of the percentage error. CONCLUSIONS: Since the use of DOCM is limited
by the necessity that portal vein is visible in CT scans, significant restriction
for patients' follow-up, we concluded that SM can be reliably employed. However,
a proper software has to be used and an estimation of SNR would be carried out.
PMID- 25130499
TI - Rapid one-step purification of single-cells encapsulated in alginate
microcapsules from oil to aqueous phase using a hydrophobic filter paper:
implications for single-cell experiments.
AB - By virtue of the biocompatibility and physical properties of hydrogel, picoliter
sized hydrogel microcapsules have been considered to be a biometric signature
containing several features similar to that of encapsulated single cells,
including phenotype, viability, and intracellular content. To maximize the
experimental potential of encapsulating cells in hydrogel microcapsules, a method
that enables efficient hydrogel microcapsule purification from oil is necessary.
Current methods based on centrifugation for the conventional stepwise rinsing of
oil, are slow and laborious and decrease the monodispersity and yield of the
recovered hydrogel microcapsules. To remedy these shortcomings we have developed
a simple one-step method to purify alginate microcapsules, containing a single
live cell, from oil to aqueous phase. This method employs oil impregnation using
a commercially available hydrophobic filter paper without multistep centrifugal
purification and complicated microchannel networks. The oil-suspended alginate
microcapsules encapsulating single cells from mammalian cancer cell lines (MCF-7,
HepG2, and U937) and microorganisms (Chlorella vulgaris) were successfully
exchanged to cell culture media by quick (~10 min) depletion of the surrounding
oil phase without coalescence of neighboring microcapsules. Cell proliferation
and high integrity of the microcapsules were also demonstrated by long-term
incubation of microcapsules containing a single live cell. We expect that this
method for the simple and rapid purification of encapsulated single-cell
microcapsules will attain widespread adoption, assisting cell biologists and
clinicians in the development of single-cell experiments.
PMID- 25130500
TI - A Comparison of mucosal surface area and villous histology in small intestines of
the Brazilian free-tailed bat (Tadarida brasiliensis) and the mouse (Mus
musculus).
AB - Studies on birds have led to the hypothesis that increased intestinal absorption
between enterocytes (paracellular) evolved as a compensation for smaller
intestinal size in fliers, which was perhaps selected to minimize the mass of
digesta carried. This hypothesis predicts that bats will also exhibit relatively
reduced intestinal size and high paracellular absorption, compared with nonflying
mammals. Published studies on three bat species indicate relatively high
paracellular absorption. One mechanism for increasing paracellular absorption per
cm2 small intestine (SI) is increased number of tight junctions (TJs) across
which paracellular absorption occurs. To our knowledge, we provide the first
comparative analysis of enterocyte size and number in flying and nonflying
mammals. Intestines of insectivorous bats Tadarida brasiliensis were compared
with Mus musculus using hematoxylin and eosin staining method. Bats had shorter
and narrower SIs than mice, and after correction for body size difference by
normalizing to mass3/4, the bats had 40% less nominal surface area than the
mouse, as predicted. Villous enhancement of surface area was 90% greater in the
bat than in the mouse, mainly because of longer villi and a greater density of
villi in bat intestines. Bat and mouse were similar in enterocyte diameter. Bats
exceeded mice by 54.4% in villous area per cm length SI and by 95% in number of
enterocytes per cm2 of the nominal surface area of the SI. Therefore, an
increased density of TJs per cm2 SI may be a mechanistic explanation that helps
to understand the high paracellular absorption observed in bats compared to
nonflying mammals.
PMID- 25130501
TI - Non-local atomic manipulation on semiconductor surfaces in the STM: the case of
chlorobenzene on Si(111)-7*7.
AB - Control over individual atoms with the scanning tunnelling microscope (STM) holds
the tantalising prospect of atomic-scale construction, but is limited by its "one
atom at a time" serial nature. "Remote control" through non-local STM
manipulation-as we have demonstrated in the case of chlorobenzene on Si(111)-7*7
offers a new avenue for future "bottom-up" nanofabrication, since hundreds of
chemical reactions may be carried out in parallel. Thus a good understanding of
the non-local manipulation process, as provided by recent experiments, is
important. Comparison of scanning tunnelling spectroscopy (STS) measurements of
the bare Si(111)-7*7 surface and chemisorbed chlorobenzene molecules with the
voltage dependence of the non-local STM-induced desorption of chlorobenzene
proves particularly instructive. For example, the chlorobenzene LUMO appears at
+0.9 V with respect to the Fermi level, whereas non-local manipulation thresholds
are found at +2.1 V and +2.7 V. This difference supports a picture in which the
voltage thresholds for non-local electron-induced desorption depend principally
on the energies of the electronic states of the surface. Furthermore, the
demonstration that the non-local process is largely insensitive to surface steps
up to five layers in height suggests that either the electron transport in this
process is subsurface in character or surface charge transport is responsible but
is in some way unaffected by the steps.
PMID- 25130502
TI - Purification of active myrosinase from plants by aqueous two-phase counter
current chromatography.
AB - INTRODUCTION: Myrosinase (thioglucoside glucohydrolase; E.C. 3.2.1.147), is a
plant enzyme of increasing interest and importance to the biomedical community.
Myrosinase catalyses the formation of isothiocyanates such as sulforaphane (from
broccoli) and 4-(alpha-l-rhamnopyranosyloxy)benzyl isothiocyanate (from moringa),
which are potent inducers of the cytoprotective phase-2 response in humans, by
hydrolysis of their abundant glucosinolate (beta-thioglucoside N-hydroxysulphate)
precursors. OBJECTIVE: To develop an aqueous two-phase counter-current
chromatography (CCC) system for the rapid, three-step purification of
catalytically active myrosinase. METHODS: A high-concentration potassium
phosphate and polyethylene glycol biphasic aqueous two-phase system (ATPS) is
used with a newly developed CCC configuration that utilises spiral-wound, flat
twisted tubing (with an ovoid cross-section). RESULTS: Making the initial crude
plant extract directly in the ATPS and injecting only the lower phase permitted
highly selective partitioning of the myrosinase complex before a short
chromatography on a spiral disk CCC. Optimum phase retention and separation of
myrosinase from other plant proteins afforded a 60-fold purification. CONCLUSION:
Catalytically active myrosinase is purified from 3-day broccoli sprouts, 7-day
daikon sprouts, mustard seeds and the leaves of field-grown moringa trees, in a
CCC system that is predictably scalable.
PMID- 25130504
TI - Are cytokeratin-positive cells in sentinel lymph nodes of patients with invasive
breast carcinomas up to 5 mm usually insignificant?
AB - AIMS: It is known that sentinel lymph nodes (SLN) may be falsely positive due to
displaced epithelial cells, particularly in cases with an underlying intraductal
papilloma. Given the low metastatic rate in pT1a carcinomas, we aimed to
investigate the effect of this phenomenon on staging. METHODS AND RESULTS: Using
morphology and immunohistochemistry, we classified the epithelial cells in the
SLN in 39 cases of pT1a carcinoma as positive for carcinoma in six, negative in
26 and undetermined in seven. Comparative morphology and immunohistochemistry
(using oestrogen receptor, ER) showed complete concordance between the primary
carcinoma and SLN in the positive cases, and discordance in the negative cases.
The primary tumours in the negative cases were ER-positive except one, in
contrast to the SLN cytokeratin-positive (CK(+) ) cells, which were ER-negative.
The exception was a case with a Her2-positive primary, in which the SLN CK(+)
cells did not stain for Her2. In these cases considered SLN-negative, either
displacement (19 cases) or an intraductal papilloma (20 cases) was identified.
Two cases showed displacement of benign and malignant cells in the biopsy. Seven
cases were indeterminate due to the small number of SLN CK(+) cells, precluding
comparison with the primary. CONCLUSION: Given the low rate of metastases in pT1a
carcinomas, the significance of SLN CK(+) cells should be resolved by comparative
morphology and immunohistochemistry to prevent erroneous upstaging.
PMID- 25130503
TI - A high polymerized grass pollen extract is efficacious and safe in a randomized
double-blind, placebo-controlled study using a novel up-dosing cluster-protocol.
AB - BACKGROUND: Cluster immunotherapy represents an interesting alternative to
conventional up-dosing schedules because it allows achieving the maintenance dose
within a shorter time interval. In this study, the efficacy and safety of cluster
immunotherapy with a high polymerized allergen extract of a grass/rye pollen
mixture have been evaluated in a randomized, double-blind, placebo-controlled,
multicenter study. METHODS: In total, 121 patients with allergic
rhinoconjunctivitis due to grass pollen were randomized 1 : 1 to verum or placebo
group. A short cluster up-dosing schedule of only 1 week was applied to achieve
the maintenance dose which was administered monthly during the study period of 1
year. Total combined symptom and medication score (TCS) was defined as primary
outcome parameter. Secondary outcome parameters were individual symptom and
medication scores, 'well days,' global improvement as well as immunological
effects and nasal allergen challenge. The safety profile was evaluated based on
the European academy of allergy and clinical immunology grading system. RESULTS:
Significant reduction in the verum compared to the placebo group (intention-to
treat, population, verum: n = 55; placebo: n = 47) was found regarding TCS (P =
0.005), rhinoconjunctivitis total symptom score (RTSS, P = 0.006), and total
rescue medication score (TRMS, P = 0.002). Additionally, secondary outcomes such
as 'well days,' nasal challenge results, and increase of specific IgG4 were in
favor of the active treatment. All systemic adverse reactions (0.8% of all
injections in the verum group) were of mild intensity. No severe reactions
related to the study medication were observed. CONCLUSION: Cluster immunotherapy
with high polymerized grass pollen extracts resulted in significant clinical
efficacy and has been shown to be a safe treatment for grass pollen-allergic
patients.
PMID- 25130505
TI - High prevalence of vitamin D deficiency and insufficiency in adolescent
inpatients diagnosed with eating disorders.
AB - OBJECTIVE: Previous studies assessing vitamin D status in adolescents with eating
disorders showed inconsistent results. The aim of the current study was to assess
vitamin D status in a large cohort of adolescent inpatients with eating disorders
and its relation to bone mineral density (BMD) and depression. METHOD: 25
Hydroxyvitamin D (25OHD), calcium, phosphorus, and alkaline phosphatase levels as
well as BMD and depression were assessed on admission in 87 inpatients (aged 16
+/- 2 years, females = 81) with eating disorders [anorexia nervosa (AN) = 64;
bulimia nervosa (BN) = 5; eating disorders not otherwise specified-binge/purge
type (EDNOS-B/P) = 18]. RESULTS: Mean 25OHD levels were 24.1 +/- 7.5 ng/ml (25.0
+/- 7.6, 25.4 +/- 9.9, and 22.0 +/- 9.9 ng/ml in patients with AB, BN, and EDNOS
B/P, respectively). Vitamin D deficiency (<15 ng/ml) was found in 7.8% of the
patients, and insufficiency (15-20 ng/ml) in 22.2%. Only 16.7% had levels >32
ng/ml, considered optimal by some experts. No associations were found between
25OHD levels and BMD or comorbid depression. 25OHD levels during winter were
significantly lower than summer levels (p < .001). Mean lumbar spine BMD z-score
in patients with AN and EDNOS-B/P type was low (-1.5 +/- 1.1) and correlated with
body mass index standard deviation score (p = .03). DISCUSSION: Adolescents with
eating disorders show a high prevalence of vitamin D deficiency and
insufficiency. Given the risk of osteoporosis in this population, 25OHD levels
found in this group may not offer optimal bone protection. Vitamin D levels
should be routinely checked and supplementation should be administered as
required.
PMID- 25130506
TI - Rethinking nasal tip support: a finite element analysis.
AB - OBJECTIVE: We employ a nasal tip finite element model (FEM) to evaluate
contributions of two of the three major tip support mechanisms: attachments
between the upper and lower lateral cartilages and attachment of the medial crura
to the caudal septum. STUDY DESIGN: The nasal tip FEM computed stress
distribution and strain energy density (SED) during nasal tip compression. We
examined the impact of attachments between the upper and lower lateral cartilages
and the attachment of the medial crura to the caudal septum on nasal tip support.
METHODS: The FEM consisted of three tissue components: bone, cartilage, and skin.
Four models were created: A) control model with attachments present at the scroll
and caudal septum; B) simulated disruption of scroll; C) simulated disruption of
medial crura attachments to caudal septum; and D) simulated disruption of scroll
and medial crura attachments to caudal septum. Spatial distribution of stress and
SED were calculated. RESULTS: The keystone, intermediate crura, caudal septum,
and nasal spine demonstrated high concentration of stress distribution. Across
all models, there was no difference in stress distribution. Disruption of the
scroll resulted in 1% decrease in SED. Disruption of the medial crura attachments
to the caudal septum resulted in 4.2% reduction in SED. Disruption of both scroll
and medial crural attachments resulted in 9.1% reduction in SED. CONCLUSION: The
nasal tip FEM is an evolving tool to study structural nasal tip dynamics and
demonstrates the loss of nasal tip support with disruption of attachments at the
scroll and nasal base. LEVEL OF EVIDENCE: N/A.
PMID- 25130507
TI - Ivermectin: panacea for resource-poor communities?
AB - The 2014 Gairdner Global Health Award was conferred for discovery of the unique
microorganism that is the sole source of the endectocidal avermectins, and the
Public sector/Private sector Partnership that developed innovative
biopharmaceuticals with immeasurably beneficial impact on public health
worldwide. Ivermectin is already labelled a 'wonder drug', essential for
campaigns to eliminate two disfiguring and devastating tropical diseases. New
uses for it are identified regularly, including possible antibacterial,
antiviral, and anticancer potential. Hundreds of millions of people are taking
ivermectin to combat various diseases and afflictions, and mass administration of
ivermectin in polyparasitised poor communities around the world is increasingly
recognised as a mechanism to easily and cost-effectively improve overall health
and quality of life for everyone.
PMID- 25130508
TI - Impact of body mass index on outcomes of laparoscopic radical prostatectomy with
long-term follow-up.
AB - OBJECTIVE: The aim of this study was to investigate the impact of body mass index
(BMI) on the functional and oncological results of patients who had undergone
laparoscopic radical prostatectomy (LRP). MATERIAL AND METHODS: In total, 1224
patients with follow-up data (>24 months) were enrolled. Patients were divided
into three groups according to BMI (kg/m(2)) as: group 1 (normal, BMI <25, n =
425), group 2 (overweight, 25 <= BMI <30, n = 594) and group 3 (obese, BMI >= 30,
n = 205). Demographic, intraoperative and postoperative data with oncological
outcomes were recorded. The impact of obesity on those parameters was evaluated
and statistical analyses were performed. RESULTS: Mean age was 63.8 +/- 6.1 years
and mean follow-up was 43.1 +/- 25.1 months (mean +/- SD). There were 425 (34.7%)
patients in group 1, 594 (48.5%) in group 2 and 205 (16.8%) in group 3. Operation
time, clinical stage and estimated blood loss were significantly higher in group
3 than in the other groups (p < 0.001, p = 0.001 and p = 0.001, respectively).
Bilateral nerve-sparing rate and bladder neck-sparing rate were significantly
decreased in group 3 compared with the other groups (p = 0.001 and p < 0.038,
respectively). Statistically significantly higher pathological stage, tumour
volume, positive surgical margin and Gleason scores were determined in group 3
compared with the other groups (p = 0.023, p = 0.018, p = 0.009 and p = 0.028,
respectively). There were similar urinary continence rates among the groups. The
rate of penetration with or without medication was significantly lower in group 3
than in the other groups (p = 0.593 and p = 0.007, respectively). CONCLUSIONS:
LRP seemed safe and effective in obese patients, with similar mean overall
survival, cancer-specific survival, complication rates and continence rates to
normal weight patients in the long term.
PMID- 25130510
TI - Diagnosis and management of atrial fibrillation: an overview.
AB - Atrial fibrillation (AF) has been defined as the new cardiovascular "epidemic".
Its prevalence is rising in developed countries, and the associated social and
economic costs are high. In the last few years, there has been an increasing
interest in understanding the mechanisms of AF and its management. New
pharmacotherapies together with novel techniques for surgical and catheter
treatment of AF have been developed, allowing the maintenance of sinus rhythm and
the alleviation of symptoms in a large number of patients with AF. However, there
are still some challenges that need to be addressed. This article gives an
overview of the current state of the art on novel techniques for diagnosis and
management of AF.
PMID- 25130511
TI - Detecting human cytomegalovirus drug resistant mutations and monitoring the
emergence of resistant strains using real-time PCR.
AB - BACKGROUND: Antiviral resistance development is a serious complication of human
cytomegalovirus virostatic therapy caused by mutations in UL 97 and/or UL54
genes. OBJECTIVES: To determinate the presence of sensitive and resistant strains
in patients developing antiviral resistance. STUDY DESIGN: We used three
different molecular biological methods for mutation analysis-restriction fragment
length polymorphism, sequencing and real-time PCR approach. RESULTS: We describe
three allogeneic hematopoietic stem cell transplant patients developing the GCV
resistant HCMV strains manifested by virostatic treatment failure. In these
patients we identified UL97 mutations L595S, A594V and A594T and monitored the
dynamics of coexisted sensitive/resistant strains. We confirmed the presence of
mixed HCMV populations and in two patients a phenomenon of sensitive strain
repopulation which occurred after 6.5 months and 1 month after removing GCV
pressure. CONCLUSIONS: Our results show changes in proportions of
sensitive/resistant subpopulations over time but other studies would be required
to demonstrate the beneficial impact of their monitoring on clinical outcome.
PMID- 25130509
TI - CHARMM-GUI Membrane Builder toward realistic biological membrane simulations.
AB - CHARMM-GUI Membrane Builder, http://www.charmm-gui.org/input/membrane, is a web
based user interface designed to interactively build all-atom protein/membrane or
membrane-only systems for molecular dynamics simulations through an automated
optimized process. In this work, we describe the new features and major
improvements in Membrane Builder that allow users to robustly build realistic
biological membrane systems, including (1) addition of new lipid types, such as
phosphoinositides, cardiolipin (CL), sphingolipids, bacterial lipids, and
ergosterol, yielding more than 180 lipid types, (2) enhanced building procedure
for lipid packing around protein, (3) reliable algorithm to detect lipid tail
penetration to ring structures and protein surface, (4) distance-based algorithm
for faster initial ion displacement, (5) CHARMM inputs for P21 image
transformation, and (6) NAMD equilibration and production inputs. The robustness
of these new features is illustrated by building and simulating a membrane model
of the polar and septal regions of E. coli membrane, which contains five lipid
types: CL lipids with two types of acyl chains and phosphatidylethanolamine
lipids with three types of acyl chains. It is our hope that CHARMM-GUI Membrane
Builder becomes a useful tool for simulation studies to better understand the
structure and dynamics of proteins and lipids in realistic biological membrane
environments.
PMID- 25130513
TI - Urodynamic testing: physiological background, setting-up, calibration and
artefacts.
AB - Urodynamics (UDS) is an interactive diagnostic study of lower urinary tract
function. It is composed of several tests that can be used to obtain functional
information about urine storage and expulsion. Its main goal is to reproduce the
patients' symptoms and determine their cause. The present article is a review of
the physiological concepts behind UDS, and explains the various normal and
abnormal forces and parameters that are measured and used during the tests to
assist the physician in making a diagnosis. It outlines the importance and
methods of the calibration of UDS equipment to optimise diagnostic accuracy and
reliability, which would have a crucial impact over the treatment's decision, and
consequently the patient's outcome.
PMID- 25130512
TI - IFNL4 polymorphism predicts response to hepatitis C treatment after liver
transplantation.
AB - BACKGROUND: Recent studies in chronic hepatitis C patients have shown that
rs368234815 polymorphism nearby IL28B is a better predictor of response to
antiviral treatment with pegylated interferon and ribavirin than IL28B
polymorphisms (rs12979860 and rs8099917). Its effect could be related to
interferon lambda 4 (IFNL4), a protein which seems to confer some paradoxical
disadvantages in hepatitis C virus (HCV) immune response. OBJECTIVES: To assess
the role of IFNL4 rs368234815 polymorphism on the response to antiviral treatment
after liver transplantation (LT). STUDY DESIGN: IFNL4 and IL28B polymorphisms
were genotyped in 86 HCV-infected LT recipients and in their donors; all patients
had undergone antiviral treatment with pegylated interferon and ribavirin after
LT. RESULTS: IFNL4 polymorphism strongly correlated with IL28B ones (p < 0.001).
The favorable IFNL4 genotype (TT/TT) was significantly more frequent among donors
than recipients (60% donors vs. 22% recipients, p <0.001). Recipient TT/TT
genotype was associated with a higher sustained virological response rate after
LT (p = 0.024). Nevertheless, the highest sustained virological response
frequency was found when both donors and recipients had favorable genotypes (73%
vs. 25%, p = 0.002), suggesting a role for donor genotype. CONCLUSIONS: Our study
demonstrates that IFNL4 rs368234815 polymorphism is an important predictor of
response to antiviral treatment in the LT setting. These findings warrant further
studies on IFNL4 role in immune response against HCV.
PMID- 25130515
TI - Bariatric surgery in the elderly: 2009-2013.
AB - BACKGROUND: Ample evidence supports the safety and effectiveness of bariatric
surgery in the general adult population but more information is needed in
patients age 60 years and older (elderly). We previously examined the outcome of
bariatric surgery performed in the elderly between 1999 and 2005 using the
University HealthSystem Consortium (UHC) Clinical Database. The aim of this study
was to analyze contemporary outcomes of bariatric surgery in the elderly and to
compare them to previous data from 1999-2005. METHODS: Using International
Classification of Diseases, 9(th) Revision diagnosis and procedure codes, we
obtained data from the UHC database for all elderly (age >60 yr) and adult
nonelderly (age 19-60 yr) patients who underwent bariatric surgery for the
treatment of morbid obesity between 2009 and 2013. Outcome measures, such as
patient characteristics, LOS, morbidity, and observed-to-expected (risk-adjusted)
mortality ratio were compared between elderly and nonelderly patients. RESULTS:
Bariatric surgery in the elderly made up 2.7% of all bariatric operations in 1999
2005. This represents an increase to 10.1% of all bariatric operations in 2009
2013. In-hospital mortality was .30% for the nonelderly and .70% for the elderly
in 1999-2005, whereas contemporary in-hospital mortality has decreased to .11%
for the nonelderly and .05% for the elderly. CONCLUSION: Our results show that
the number of bariatric procedures performed in the elderly is increasing and now
represents 10% of all bariatric operations performed at academic centers. In
hospital mortality in bariatric surgery in the elderly has improved so much that
it is now even better than in-hospital mortality in the nonelderly in 1999-2005.
PMID- 25130514
TI - TNF-alpha-induced cardiomyocyte apoptosis contributes to cardiac dysfunction
after coronary microembolization in mini-pigs.
AB - This experimental study was designed to clarify the relationship between
cardiomyocyte apoptosis and tumour necrosis factor-alpha (TNF-alpha) expression,
and confirm the effect of TNF-alpha on cardiac dysfunction after coronary
microembolization (CME) in mini-pigs. Nineteen mini-pigs were divided into three
groups: sham-operation group (n = 5), CME group (n = 7) and adalimumab pre
treatment group (n = 7; TNF-alpha antibody, 2 mg/kg intracoronary injection
before CME). Magnetic resonance imaging (3.0-T) was performed at baseline, 6th
hour and 1 week after procedure. Cardiomyocyte apoptosis was detected by cardiac
TUNEL staining, and caspase-3 and caspase-8 were detected by RT-PCR and
immunohistochemistry. Furthermore, serum TNF-alpha, IL-6 and troponin T were
analysed, while myocardial expressions of TNF-alpha and IL-6 were detected. Both
TNF-alpha expression (serum level and myocardial expression) and average number
of apoptotic cardiomyocyte nuclei were significantly increased in CME group
compared with the sham-operation group. Six hours after CME, left ventricular end
systolic volume (LVESV) was increased and the left ventricular ejection fraction
(LVEF) was decreased in CME group. Pre-treatment with adalimumab not only
significantly improved LVEF after CME (6th hour: 54.9 +/- 2.3% versus 50.4 +/-
3.9%, P = 0.036; 1 week: 56.7 +/- 4.2% versus 52.7 +/- 2.9%, P = 0.041), but also
suppressed cardiomyocyte apoptosis and the expression of caspase-3 and caspase-8.
Meanwhile, the average number of apoptotic cardiomyocytes nuclei was inversely
correlated with LVEF (r = -0.535, P = 0.022). TNF-alpha-induced cardiomyocyte
apoptosis is likely involved in cardiac dysfunction after CME. TNF-alpha antibody
therapy suppresses cardiomyocyte apoptosis and improves early cardiac function
after CME.
PMID- 25130516
TI - Mesenteric venous thrombosis following vertical sleeve gastrectomy in an
adolescent.
PMID- 25130517
TI - Comment on: POSSUM and p-POSSUM overestimate morbidity and mortality in
laparoscopic bariatric surgery.
PMID- 25130519
TI - CD8+ tumour-infiltrating lymphocytes and COX2 expression may predict relapse in
differentiated thyroid cancer.
AB - BACKGROUND/OBJECTIVE: There is an increasing rate of papillary thyroid carcinomas
that may never progress to cause symptoms or death. Predicting outcome and
determining tumour aggressiveness could help diminish the number of patients
submitted to aggressive treatments. We aimed to evaluate whether markers of the
immune system response and of tumour-associated inflammation could predict
outcome of differentiated thyroid cancer (DTC) patients. DESIGN: Retrospective
cohort study. PATIENTS: We studied 399 consecutive patients, including 325
papillary and 74 follicular thyroid carcinomas. MEASUREMENTS: Immune cell markers
were evaluated using immunohistochemistry, including tumour-associated
macrophages (CD68) and subsets of tumour-infiltrating lymphocytes (TIL), such as
CD3, CD4, CD8, CD16, CD20, CD45RO, GRANZYME B, CD69 and CD25. We also
investigated the expression of cyclooxygenase 2 (COX2) in tumour cells and the
presence of concurrent lymphocytic infiltration characterizing chronic
thyroiditis. RESULTS: Concurrent lymphocytic infiltration characterizing chronic
thyroiditis was observed in 29% of the cases. Among all the immunological
parameters evaluated, only the enrichment of CD8+ lymphocytes (P = 0.001) and
expression of COX2 (P =0.01) were associated with recurrence. A multivariate
model analysis identified CD8+ TIL/COX2 as independent risk factor for
recurrence. A multivariate analysis using Cox's proportional-hazards model
adjusted for the presence of concurrent chronic thyroiditis demonstrated that the
presence of concurrent chronic thyroiditis had no effect on prognostic prediction
mediated by CD8+ TIL and COX2. CONCLUSION: In conclusion, we suggest the use of a
relatively simple pathology tool to help select cases that may benefit of a more
aggressive approach sparing the majority of patients from unnecessary procedures.
PMID- 25130520
TI - Impulsivity, risk-taking, and distractibility in rats exhibiting robust
conditioned orienting behaviors.
AB - When a neutral cue is followed by a significant event such as food delivery, some
animals become engaged with the cue itself and acquire cue-directed behaviors.
One type of cue-directed behavior is observed following insertion of a lever used
as a conditioned stimulus (CS). Rats showing robust approach behavior to the
lever also display impulsivity and altered attention, as compared to rats showing
behavior directed toward the reward delivery location. The current study used a
light CS to categorize rats' propensity for cue-directed behavior, and assessed
whether individual differences in impulsivity and related behaviors still
emerged. During the light-food pairings, some rats displayed enhanced rearing or
orienting to the light (Orienters) prior to showing food cup approach behavior,
while other rats only showed food cup approach behavior (Nonorienters). Our
results showed that Orienters made more impulsive and risky decisions in two
different choice tasks, and were quicker to leave a familiar dark environment to
enter a novel bright field. Orienters also showed less accurate target detection
when a visual distractor was introduced during an attentional challenge. Our
current study suggests that light CS-induced rearing/orienting behavior might not
necessarily share an identical mechanism with lever CS-approach behavior in
predicting impulsivity-related behaviors.
PMID- 25130518
TI - Cost effectiveness of telecare management for pain and depression in patients
with cancer: results from a randomized trial.
AB - OBJECTIVE: Pain and depression are prevalent and treatable symptoms among
patients with cancer, yet they are often undetected and undertreated. The Indiana
Cancer Pain and Depression (INCPAD) trial demonstrated that telecare management
can improve pain and depression outcomes. This article investigates the
incremental cost effectiveness of the INCPAD intervention. METHODS: The INCPAD
trial was conducted in 16 community-based urban and rural oncology practices in
Indiana. Of the 405 participants, 202 were randomized to the intervention group
and 203 to the usual-care group. Intervention costs were determined, and
effectiveness outcomes were depression-free days and quality-adjusted life years.
RESULTS: The intervention group was associated with a yearly increase of 60.3
depression-free days (S.E. = 15.4; P < 0.01) and an increase of between 0.033 and
0.066 quality-adjusted life years compared to the usual care group. Total cost of
the intervention per patient was US$1189, which included physician, nurse care
manager and automated monitoring set-up and maintenance costs. Incremental cost
per depression-free day was US$19.72, which yields a range of US$18,018 to
US$36,035 per quality-adjusted life year when converted to that metric. When
measured directly, the incremental cost per quality-adjusted life year ranged
from US$10,826 based on the modified EQ-5D to US$73,286.92 based on the SF-12.
CONCLUSION: Centralized telecare management, coupled with automated symptom
monitoring, appears to be a cost effective intervention for managing pain and
depression in cancer patients.
PMID- 25130522
TI - Anterior guidance--movement and stability.
AB - Instability of our orthodontic treatment is not uncommon, in particular in the
anterior teeth. Given that the mandible is constantly in movement and that the
lower and upper teeth regularly meet head-on during normal functioning, one might
ask: are the static and normative end of treatment objectives we generally target
sufficient to ensure treatment stability?
PMID- 25130524
TI - Between a rock and a hard place: getting families to change behaviors to reduce
pediatric stone disease recurrence.
PMID- 25130525
TI - Transobturator versus retropubic approach for a mid urethral sling.
PMID- 25130523
TI - A lower intensity of treatment may underlie the increased risk of thrombosis in
young patients with masked polycythaemia vera.
AB - In patients who do not meet the World Health Organization (WHO) criteria for
overt polycythaemia vera (PV), a diagnosis of masked PV (mPV) can be determined.
A fraction of mPV patients may display thrombocytosis, thus mimicking essential
thrombocythaemia (ET). No previous studies have examined clinical outcomes of mPV
among young JAK2-mutated patients. We analysed a retrospective cohort of 538 JAK2
mutated patients younger than 40 years, after a re-assessment of the diagnosis
according to the haemoglobin threshold for mPV. In this cohort of patients, 97
(18%) met the WHO criteria for PV, 66 patients (12%) were classified as mPV and
375 (70%) as JAK2-mutated ET. Surprisingly, a significant difference in the
incidence of thrombosis was found when comparing mPV versus overt PV patients (P
= 0.04). In multivariate analysis, the only factor accounting for the difference
in the risk of thrombosis was the less frequent use of phlebotomies and
cytoreduction in mPV patients compared to those with overt PV. Thus, we emphasize
the need for the identification of mPV in young JAK2-mutated patients in order to
optimize their treatments.
PMID- 25130528
TI - Editorial comment.
PMID- 25130529
TI - Outcomes of retroperitoneal lymph node dissection for the most challenging cases.
PMID- 25130530
TI - Epigenetic factors affect tumor initiation, progression and recurrence.
PMID- 25130531
TI - Complications of stone disease in the 21st century--can noninvasive and minimally
invasive treatment modalities improve the overall renal health of stone formers?
PMID- 25130532
TI - Water nanodroplets make a greater contribution to facial skin moisture levels in
air-conditioned rooms during winter than in summer.
AB - BACKGROUND/PURPOSE: By performing experiments in air-conditioned chamber, we
previously demonstrated that the presence of water nanodroplets (mist) improved
facial skin moisture levels without reducing water loss from the facial skin
surface or inducing excessive humidity. Some previous studies have demonstrated
that the epidermis is a less effective barrier to water in winter because the
corneocytes that comprise facial skin become smaller in winter as skin turnover
increases in cold environments. We hypothesized that it would be easier for mist
to penetrate into the facial stratum corneum (SC) in winter than in summer. In
the present study, we investigated the ability of mist to improve facial skin
moisture levels in winter and summer. METHODS: We examined transepidermal water
loss (TEWL) as an index of barrier function and skin conductance as an index of
SC hydration at the forehead, lateral canthus, and cheeks in eight healthy
Japanese females (mean +/- SD: 45.5 +/- 3.2 years) in the presence or absence of
mist in February-March and July. RESULTS: In the absence of mist, skin
conductance at the forehead and lateral canthus was significantly higher in
summer than in winter, but these seasonal differences were diminished in the
presence of mist. In the presence of mist, skin conductance was increased in
winter and decreased in summer at the lateral canthus; however, these changes
were not significant. Thus, our findings suggest that mist penetrates into the SC
and improves skin moisture levels in winter. CONCLUSION: We demonstrated that it
is easier for mist to penetrate into the SC at the lateral canthus during winter
than in summer. Thus, mist is expected to improve facial moisture levels in
winter by penetrating into and remaining in the SC. Hence, mist could be used to
help prevent facial skin from becoming dry in air-conditioned rooms during
winter.
PMID- 25130534
TI - Inpatient pharmacological sleep aid utilization is common at a tertiary medical
center.
AB - BACKGROUND: Sleep is known to be poor in the hospital. Patients frequently
request pharmacological sleep aids, despite the risk of altered mental status
(delirium) and falls. Little is known about the scope of pharmacological sleep
aid use in hospitalized patients. METHODS: We performed a single center,
retrospective review of all patients admitted to the general adult (age >18
years) medical and surgical units of a tertiary care center during a recent 2
month period (January 2013-February 2013). Review of the electronic medication
administration system was performed to assess for medications administered for
sleep. RESULTS: Of 642 unique admissions, 168 patients (26.2%) received a
medication for sleep. Most (n = 115, 68.5%) had no known history of insomnia or
regular prior sleep medication use. Patients most frequently were treated with
trazodone (30.4%; median dose, 50 mg; range, 12.5-450 mg), lorazepam (24.4%;
median, 0.5 mg; range, 0.25-2 mg), and zolpidem tartrate (17.9%; median, 10 mg;
range, 2.5-10 mg). Of the medications given, 36.7% were given early (before 9 pm)
or late (after midnight). Of patients not known to be previously taking a
pharmacological sleep aid, 34.3% of them were discharged with a prescription for
one. CONCLUSIONS: Despite increasing evidence of risks such as delirium or falls,
pharmacological sleep aid use in general wards remains common, even in elderly
patients. Medication administration time is frequently suboptimal. Many
previously sleep medication-naive patients leave the hospital with a sleep aid
prescription. Further research is needed to understand the factors that
contribute to the high rate of sleep medication use in hospitalized patients.
PMID- 25130536
TI - Curcumin attenuates Cr(VI)-induced ascites and changes in the activity of
aconitase and F(1)F(0) ATPase and the ATP content in rat liver mitochondria.
AB - Occupational and environmental exposure to potassium dichromate (K2Cr2O7), a
hexavalent chromium compound, can result in liver damage associated with
oxidative stress and mitochondrial dysfunction. The purpose of this study was to
evaluate the effect of the antioxidant curcumin (400 mg/kg b.w.) on the K2Cr2O7
induced injury, with special emphasis on ascitic fluid accumulation and oxidative
phosphorylation mitochondrial enzymes and the adenosine triphosphate (ATP) levels
in isolated mitochondria from livers of rats treated with K2Cr2O7 (15 mg/kg
b.w.). Thus, curcumin attenuated the ascites generation, prevented the decrease
in the activities of aconitase and F1F0 ATPase, and maintained the ATP levels.
The activity of complex II was not completely reestablished by curcumin, whereas
complexes III and IV activities were unchanged.
PMID- 25130535
TI - Nutrient intakes associated with elevated serum C-reactive protein concentrations
in normal to underweight breastfeeding women in Northern Kenya.
AB - OBJECTIVES: Low-grade elevation of C-reactive protein (CRP) is a non-specific
inflammatory marker, used as a predictor for cardiovascular disease development
and chronic inflammatory risks. Research investigating dietary influences on
inflammation has focused primarily on the relationship between dietary
characteristics, CRP elevation and BMI in the populations at greatest risk for
cardiovascular disease, namely those in the overweight and obese ranges, often in
clinical settings and/or among those middle aged or older, leaving little
information about normal to underweight populations of reproductive age in
ecological settings. This study evaluates impacts of dietary nutrients on serum
CRP levels in a population of predominantly underweight to normal weight adult
women experiencing the additional nutritional demands of lactation. METHODS: Data
from non-overweight breastfeeding Ariaal women of Kenya collected in 2006 were
used (n = 194). Logistic regression models were applied using low-grade CRP
elevation (hsCRP > 3 mg/L) as the outcome variable and dietary nutrients, age,
BMI, and serum retinol as predictors. RESULTS: Models showed that energy intake
(Kcal) and age were positive predictors of CRP elevation while folate intake,
total vitamin A intake, and serum retinol concentration were protective against
CRP elevation. Unlike previous studies among higher BMI populations, this study
found no significant effect of dietary lipids/fatty acids or BMI on CRP
elevation. CONCLUSIONS: The effects of specific dietary nutrients on inflammatory
status may vary with BMI or, in women, reproductive status. Further research
should investigate the role of dietary fats, fatty acids, and antioxidant
vitamins across populations with a wide range of BMI, including postpartum women.
PMID- 25130533
TI - Epigenetic mechanisms of memory formation and reconsolidation.
AB - Memory consolidation involves transcriptional control of genes in neurons to
stabilize a newly formed memory. Following retrieval, a once consolidated memory
destabilizes and again requires gene transcription changes in order to
restabilize, a process referred to as reconsolidation. Understanding the
molecular mechanisms of gene transcription during the consolidation and
reconsolidation processes could provide crucial insights into normal memory
formation and memory dysfunction associated with psychiatric disorders. In the
past decade, modifications of epigenetic markers such as DNA methylation and
posttranslational modifications of histone proteins have emerged as critical
transcriptional regulators of gene expression during initial memory formation and
after retrieval. In light of the rapidly growing literature in this exciting area
of research, we here examine the most recent and latest evidence demonstrating
how memory acquisition and retrieval trigger epigenetic changes during the
consolidation and reconsolidation phases to impact behavior. In particular we
focus on the reconsolidation process, where we discuss the already identified
epigenetic regulators of gene transcription during memory reconsolidation, while
exploring other potential epigenetic modifications that may also be involved, and
expand on how these epigenetic modifications may be precisely and temporally
controlled by important signaling cascades critical to the reconsolidation
process. Finally, we explore the possibility that epigenetic mechanisms may serve
to regulate a system or circuit level reconsolidation process and may be involved
in retrieval-dependent memory updating. Hence, we propose that epigenetic
mechanisms coordinate changes in neuronal gene transcription, not only during the
initial memory consolidation phase, but are triggered by retrieval to regulate
molecular and cellular processes during memory reconsolidation.
PMID- 25130538
TI - Bioreducible branched polyethyleneimine derivatives physically loaded with
hydrophobic pheophorbide A: preparation, characterization, and light-induced
cytotoxicity.
AB - Branched-type hydrophilic polyethyleneimine derivatives (i.e., bPEI derivatives)
are developed polymeric carriers for photodynamic therapy. Their chemical
structures which contain pH-tunable hydrophobic/hydrophilic cavities enable
efficient loading of hydrophobic drugs in basic pH environments. Intracellular
stimuli trigger the release of the loaded drugs in bPEI derivatives. As expected,
the hydrophobic photosensitizer known as pheophorbide A (PheoA) is solubilized by
physical loading in the inner hydrophobic spaces of bPEI derivatives in
environments with basic pH values. Interestingly, acidic pH environments induce
aggregation, resulting in poor release of the loaded PheoA as well as in quenched
photo-activity of the PheoA-loaded polymers. However, when reducible polycation
derivatives of bPEI are used (i.e., RPC-bPEI), intracellular thiols degrade the
disulfide linkages in the polymers, resulting in rapid PheoA release.
Particularly, a RPC-bPEI containing 6 wt% PheoA (i.e., RPC-bPEI(0.8 kDa)
PheoA(6%)) respond remarkably well to light exposure and display large
differences between dark toxicity and light-induced toxicity. Cellular uptake of
RPC-bPEI(0.8 kDa)-PheoA(6%) is approximately sevenfold to ninefold lower than
that of free PheoA. Nevertheless, the photo-toxicity of RPC-bPEI(0.8 kDa)
PheoA(6%) was only two- to sixfold less potent than that of free PheoA. These
results suggest that reducible bPEI materials may act as potential solubilizers
and carriers for low-molecular-weight hydrophobic anti-cancer drugs.
PMID- 25130537
TI - The PAX2-null immunophenotype defines multiple lineages with common expression
signatures in benign and neoplastic oviductal epithelium.
AB - The oviducts contain high-grade serous cancer (HGSC) precursors (serous tubal
intraepithelial neoplasia or STINs), which are gamma-H2AX(p) - and TP53 mutation
positive. Although they express wild-type p53, secretory cell outgrowths (SCOUTs)
are associated with older age and serous cancer; moreover, both STINs and SCOUTs
share a loss of PAX2 expression (PAX2(n) ). We evaluated PAX2 expression in
proliferating adult and embryonic oviductal cells, normal mucosa, SCOUTs,
Walthard cell nests (WCNs), STINs, and HGSCs, and the expression of genes chosen
empirically or from SCOUT expression arrays. Clones generated in vitro from
embryonic gynaecological tract and adult Fallopian tube were Krt7(p) /PAX2(n)
/EZH2(p) and underwent ciliated (PAX2(n) /EZH2(n) /FOXJ1(p) ) and basal (Krt7(n)
/EZH2(n) /Krt5(p) ) differentiation. Similarly, non-ciliated cells in normal
mucosa were PAX2(p) but became PAX2(n) in multi-layered epithelium undergoing
ciliated or basal (WCN) cell differentiation. PAX2(n) SCOUTs fell into two
groups: type 1 were secretory or secretory/ciliated with a 'tubal' phenotype and
were ALDH1(n) and beta-catenin(mem) (membraneous only). Type 2 displayed a
columnar to pseudostratified (endometrioid) phenotype, with an EZH2(p) , ALDH1(p)
, beta-catenin(nc) (nuclear and cytoplasmic), stathmin(p) , LEF1(p) , RCN1(p) ,
and RUNX2(p) expression signature. STINs and HGSCs shared the type 1
immunophenotype of PAX2(n) , ALDH1(n) , beta-catenin(mem) , but highly expressed
EZH2(p) , LEF1(p) , RCN1(p) , and stathmin(p) . This study, for the first time,
links PAX2(n) with proliferating fetal and adult oviductal cells undergoing basal
and ciliated differentiation and shows that this expression state is maintained
in SCOUTs, STINs, and HGSCs. All three entities can demonstrate a consistent
perturbation of genes involved in potential tumour suppressor gene silencing
(EZH2), transcriptional regulation (LEF1), regulation of differentiation (RUNX2),
calcium binding (RCN1), and oncogenesis (stathmin). This shared expression
signature between benign and neoplastic entities links normal progenitor cell
expansion to abnormal and neoplastic outgrowth in the oviduct and exposes a
common pathway that could be a target for early prevention.
PMID- 25130539
TI - Parenteral administration of GnRH constructs and adjuvants: immune responses and
effects on reproductive tissues of male mice.
AB - Two gonadotrophin releasing hormone (GnRH) constructs prepared by either chemical
conjugation to keyhole limpet hemocyanin (GnRH-KLH) or as an expressed
recombinant fusion protein (Multimer) were evaluated with or without adjuvants
(immunostimulating complexes, ISCOMs, or cytosine-phosphate-guanosine
oligodeoxynucleotides, CpG ODNs). After subcutaneous administration to Balb/c
male mice at Weeks 0, 2 and 4, these preparations were assessed for induction of
immune responses and effects on reproductive organs. GnRH-KLH plus ISCOMs
formulation induced strong IgG immune responses from Week 4 through Week 12
resulting in consistent reproductive organ atrophy by Week 12 after subcutaneous
administration. GnRH-KLH plus CpG ODNs generated immune responses but no atrophy
of reproductive tissues by Week 12. Multimer plus ISCOMs induced poor immune
responses and no effects on reproductive tissues by Week 12. In the absence of
additional adjuvant, none of the GnRH constructs induced reproductive organ
atrophy. GnRH-KLH induced stronger immune responses when formulated with ISCOMs
or CpG ODN compared to Multimer. GnRH-KLH with ISCOMs could be an effective
colloidal alternative for emulsion GnRH vaccine formulations.
PMID- 25130540
TI - Complete protection against lethal challenge of novel H7N9 virus with
heterologous inactivated H7 vaccine in mice.
AB - A prototype H7 influenza vaccine constructed based on the H7N7 outbreak in 2003
was tested for the protective efficacy against the novel H7N9 virus in a lethal
murine challenge model. Serum samples from vaccinated mice showed significant
neutralizing activity against the H7N9 virus and the mice were completely
protected with no significant weight loss. The results have direct implications
on how to overcome potential vaccine shortage and identify donors for immune sera
for passive immunization.
PMID- 25130541
TI - Mesochanneled hierarchically porous aluminosiloxane aerogel microspheres as a
stable support for pH-responsive controlled drug release.
AB - The molecular-scale self-assembly of a 3D aluminosiloxane (Al-O-Si) hybrid gel
network was successfully performed via the cocondensation of hydrolyzed alumina
(AlOOH) and (3-aminopropyl)trimethoxysilane (APS). It was transformed into a
microspherical aerogel framework of Al-O-Si containing mesochannels with tunable
hierarchically bimodal meso/macroporosities by a subcritical drying technique.
Good homogeneity of AlOOH and APS brought during the synthesis guaranteed a
uniform distribution of two metal oxides in a single body. A systematic
characterization of the aerogel support was carried out using FTIR, SEM, TEM,
nitrogen adsorption/desorption analysis, WAXS, SAXS, and xi-potential measurement
in order to explore the material for drug uptake and release. The drug loading
and release capacity and chemical stability of an aluminosiloxane aerogel were
studied using two nonsteroidal antiinflammatory drugs, ibuprofen and aspirin. A
comprehensive evaluation of the aluminosiloxane aerogel with ordered mesoporous
MCM-41 was also performed. Aerogel supports showed a high drug loading capacity
and a pH-responsive controlled-release property compared to MCM-41. Meanwhile,
kinetic modeling studies indicate that the drug releases with a zero-order
profile following the Korsmeyer-Peppas model. The biocompatibility of
aluminosiloxane aerogels was established via ex vivo and in vivo studies. We also
outline the use of aluminosiloxane aerogel as a support for a possible 3D matrix
for an osteoconductive structure for bone tissue engineering.
PMID- 25130542
TI - Proteomic Profiling of Invasive Ductal Carcinoma (IDC) using Magnetic Beads-based
Serum Fractionation and MALDI-TOF MS.
AB - AIM: To reveal the serum proteomic profiling of intraductal carcinoma (IDC)
patients in China, establish a serum proteome fractionation technique for
choosing magnetic beads for proteomic analysis in breast cancer research; and
identify differentially expressed peptides (m/z; P < 0.0001) as potential
biomarkers of early IDCs. METHODS: We used two different kinds of magnetic beads
(magnetic bead-based weak cation exchange chromatography (MB-WCX) and immobilized
metal ion affinity chromatography (MB-IMAC-Cu)) to analyze 32 patients with early
stage (stages I-II) IDC and 32 healthy control serum samples for proteomic
profiling by matrix-assisted laser desorption/ionization time-of-flight mass
spectrometry (MALDI-TOF MS) analysis. The mass spectra, analyzed using
ClinProTools software, distinguished between IDC patients and healthy individuals
based on k-nearest neighbor genetic algorithm. RESULTS: The serum samples
purified in the MB-WCX group provided better proteomic patterns than the MB-IMAC
Cu group. The samples purified by MB-WCX had better average peak numbers, higher
peak intensities, and better capturing ability of low abundance proteins or
peptides in serum samples. In addition, the MB-WCX and MB-IMAC-Cu purification
methods, followed MALDI-TOF MS identification and use of ClinProTools software
accurately distinguished patients with early stage IDC from healthy individuals.
CONCLUSION: Serum proteomic profiling by MALDI-TOF MS is a novel potential tool
for the clinical diagnosis of patients with IDC in China.
PMID- 25130543
TI - The vertebrate corneal epithelium: from early specification to constant renewal.
AB - BACKGROUND: The cornea is an ectodermal/neural crest derivative formed through a
cascade of molecular mechanisms to give rise to the specific optical features
necessary for its refractory function. Moreover, during cornea formation and
maturation, epithelial stem cells are sequestered to ensure a constant source for
renewal in the adult. RESULTS: Recent progress in the molecular and stem cell
biology of corneal morphogenesis and renewal shows that it can serves as a
paradigm for epithelial /mesenchymal organ biology. This review will synthesize
historical knowledge together with recent data to present a consistent overview
of cornea specification, formation, maturation, and maintenance. CONCLUSIONS:
This should be of interest not only to developmental biologists but also
ophthalmologists, as several human vision problems are known to be rooted in
defects in corneal development.
PMID- 25130545
TI - The disintegrin and metalloproteinase ADAM10 mediates a canonical Notch-dependent
regulation of IL-6 through Dll4 in human endothelial cells.
AB - Although the involvement of the disintegrin and metalloproteinase ADAM10 in
several areas of vascular biology is now clearly established, its role in
vascular inflammation and in Notch signaling at the endothelial level remains
unclear. In this study, we demonstrated that ADAM10 specifically localizes in the
CD31(+) endothelial cells (ECs) in normal human cardiac tissues and in cultured
primary arterial ECs. In vitro, ADAM10 drives a specific regulation of the Notch
pathway in vascular ECs. Using an ADAM10 gain and loss of function approach we
show an ADAM10-dependent regulation of Dll1 and Dll4 expression in association
with changes in Hes1 and Hey1 expression. We also identified IL-6, IL-8, MCP-1
and sVCAM-1 as novel targets of ADAM10 upon inflammation. Although Notch pathway
does not seem to be required for the production of IL-8, MCP-1 and sVCAM-1, the
release of IL-6 by ECs occurred through ADAM10 and a canonical Notch signaling
pathway, dependent of gamma-secretase activity. Moreover, sustained expression of
Dll4 mediated by ADAM10 elicits an increased release of IL-6 suggesting a strong
implication of the specific Dll4 signaling in this mechanism. Modulation of IL-6
mediated by ADAM10/Notch signaling required PI3K activity. Thus, our findings
suggest that ADAM10/Dll4 signaling is a major signaling pathway in ECs driving
inflammatory events involved in inflammation and immune cell recruitment.
PMID- 25130544
TI - Distinct mechanisms of cell-kill by triapine and its terminally dimethylated
derivative Dp44mT due to a loss or gain of activity of their copper(II)
complexes.
AB - Triapine, currently being evaluated as an antitumor agent in phase II clinical
trials, and its terminally dimethylated derivative Dp44mT share the alpha-pyridyl
thiosemicarbazone backbone that functions as ligands for transition metal ions.
Yet, Dp44mT is approximately 100-fold more potent than triapine in cytotoxicity
assays. The aims of this study were to elucidate the mechanisms underlying their
potency disparity and to determine their kinetics of cell-kill in culture to aid
in the formulation of their clinical dosing schedules. The addition of Cu(2+)
inactivated triapine in a 1:1 stoichiometric fashion, while it potentiated the
cytotoxicity of Dp44mT. Clonogenic assays after finite-time drug-exposure
revealed that triapine produced cell-kill in two phases, one completed within 20
min that caused limited cell-kill, and the other occurring after 16 h of exposure
that produced extensive cell-kill. The ribonucleotide reductase inhibitor
triapine at 0.4 MUM caused immediate complete arrest of DNA synthesis, whereas
Dp44mT at this concentration did not appreciably inhibit DNA synthesis. The
inhibition of DNA synthesis by triapine was reversible upon its removal from the
medium. Cell death after 16 h exposure to triapine paralleled the appearance of
phospho-(gamma)H2AX, a marker of DNA double-strand breaks induced by collapse of
DNA replication forks after prolonged replication arrest. In contrast to
triapine, Dp44mT produced robust cell-kill within 1h in a concentration-dependent
manner. The short-term action of both agents was prevented by thiols, indicative
of the involvement of reactive oxygen species. The time dependency in the
production of cell-kill by triapine should be considered in treatment regimens.
PMID- 25130546
TI - Identification of one-electron reductases that activate both the hypoxia prodrug
SN30000 and diagnostic probe EF5.
AB - SN30000 is a second-generation benzotriazine-N-oxide hypoxia-activated prodrug
scheduled for clinical trial. Previously we showed that covalent binding of the
hypoxia probe EF5 predicts metabolic activation of SN30000 in a panel of cancer
cell lines under anoxia, suggesting that they are activated by the same
reductases. However the identity of these reductases is unknown. Here, we test
whether forced expression of nine oxidoreductases with known or suspected roles
in bioreductive prodrug metabolism (AKR1C3, CYB5R3, FDXR, MTRR, NDOR1, NOS2A,
NQO1, NQO2 and POR) enhances oxic or anoxic reduction of SN30000 and EF5 by
HCT116 cells. Covalent binding of (14)C-EF5 and reduction of SN30000 to its 1
oxide and nor-oxide metabolites was highly selective for anoxia in all lines,
with significantly elevated anoxic metabolism of both compounds in lines over
expressing POR, MTRR, NOS2A or NDOR1. There was a strong correlation between EF5
binding and SN30000 metabolism under anoxia across the cell lines (R(2)=0.84,
p=0.0001). Antiproliferative potency of SN30000 under anoxia was increased most
strongly by overexpression of MTRR and POR. Transcript abundance in human
tumours, evaluated using public domain mRNA expression data, was highest for
MTRR, followed by POR, NOS2A and NDOR1, with little variation between tumour
types. Immunostaining of tissue microarrays demonstrated variable MTRR protein
expression across 517 human cancers with most displaying low expression. In
conclusion, we have identified four diflavin reductases (POR, MTRR, NOS2A and
NDOR1) capable of reducing both SN30000 and EF5, further supporting use of 2
nitroimidazole probes to predict the ability of hypoxic cells to activate
SN30000.
PMID- 25130547
TI - Zinc: an underappreciated modulatory factor of brain function.
AB - The divalent cation, zinc is the second most abundant metal in the human body and
is indispensable for life. Zinc concentrations must however, be tightly regulated
as deficiencies are associated with multiple pathological conditions while an
excess can be toxic. Zinc plays an important role as a cofactor in protein
folding and function, e.g. catalytic interactions, DNA recognition by zinc finger
proteins and modulation ion channel activity. There are 24 mammalian proteins
specific for zinc transport that are subdivided in two groups with opposing
functions: ZnT proteins reduce cytosolic zinc concentration while ZIP proteins
increase it. The mammalian brain contains a significant amount of zinc, with 5
15% concentrated in synaptic vesicles of glutamatergic neurons alone. Accumulated
in these vesicles by the ZnT3 transporter, zinc is released into the synaptic
cleft at concentrations from nanomolar at rest to high micromolar during active
neurotransmission. Low concentrations of zinc modulate the activity of a
multitude of voltage- or ligand-gated ion channels, indicating that this divalent
cation must be taken into account in the analysis of the pathophysiology of CNS
disorders including epilepsy, schizophrenia and Alzheimer's disease. In the
context of the latest findings, we review the role of zinc in the central nervous
system and discuss the relevance of the most recent association between the zinc
transporter, ZIP8 and schizophrenia. An enhanced understanding of zinc
transporters in the context of ion channel modulation may offer new avenues in
identifying novel therapeutic entities that target neurological disorders.
PMID- 25130548
TI - Should we encourage exercise and sports in children and adolescents with cancer?
PMID- 25130550
TI - Asymmetric synthesis of agrochemically attractive trifluoromethylated
dihydroazoles and related compounds under organocatalysis.
AB - The unique, partially saturated, fluorinated five-membered heterocyclic
compounds, trifluoromethylated dihydroazoles, and their derivatives, have emerged
as a new class of heterocycles with remarkable biological activities in the 21st
century. Despite their small molecular structures, a single sterically demanding
tetrasubstituted trifluoromethylated stereogenic carbon center has prevented
chemists from achieving the asymmetric synthesis of these compounds. In this
account, we describe our recent progress in the catalytic asymmetric synthesis of
a series of trifluoromethylated heterocycles, such as isoxazolines and pyrrolines
having a stereogenic carbon center, based on organocatalysis. Our protocols have
advantages in terms of employing inexpensive reagents and organocatalysts and
they would be useful for industrial production.
PMID- 25130549
TI - Measuring sleep need.
PMID- 25130551
TI - The influence of life-history strategy on genetic differentiation and lineage
divergence in darters (Percidae: Etheostomatinae).
AB - Recent studies determined that darters with specialized breeding strategies can
exhibit deep lineage divergence over fine geographic scales without apparent
physical barriers to gene flow. However, the extent to which intrinsic
characteristics interact with extrinsic factors to influence population
divergence and lineage diversification in darters is not well understood. This
study employed comparative phylogeographic and population genetic methods to
investigate the influence of life history on gene flow, dispersal ability, and
lineage divergence in two sympatric sister darters with differing breeding
strategies. Our results revealed highly disparate phylogeographic histories,
patterns of genetic structure, and dispersal abilities between the two species
suggesting that life history may contribute to lineage diversification in
darters, especially by limiting dispersal among large river courses. Both species
also showed striking differences in demographic history, indicating that
extrinsic factors differentially affected each species during the Pleistocene.
Collectively, our results indicate that intrinsic and extrinsic factors have
influenced levels of gene flow among populations within both species examined.
However, we suggest that life-history strategy may play a more important role in
lineage diversification in darters than previously appreciated, a finding that
has potentially important implications for understanding diversification of the
rich North American freshwater fish fauna.
PMID- 25130552
TI - Reply: heart donation and the Grinch effect.
PMID- 25130553
TI - Left ventricular myocardial response to exercise in children after heart
transplant.
AB - BACKGROUND: Data on myocardial response to exercise after pediatric heart
transplant (HTx) are limited. In this study we used semi-supine bicycle ergometry
(SSCE) stress echocardiography to evaluate left ventricular (LV) systolic and
diastolic reserve in pediatric HTx recipients. METHODS: Forty-three HTx patients
and 23 controls underwent stepwise SSCE stress echocardiography. Color tissue
Doppler imaging (TDI) peak systolic (s') and early diastolic (e') velocities in
the LV lateral wall and basal septum, and LV peak global longitudinal and
circumferential strain were measured at rest and during different stages of
exercise. LV myocardial acceleration during isovolumic contraction (IVA) was
measured at incremental heart rates (HRs) to determine the force-frequency
relationship (FFR). RESULTS: At rest, compared with controls, HTx patients showed
lower TDI velocities in the basal septum (s': 4.7 +/- 1.1 vs 5.8 +/- 0.8 cm/s, p
= 0.002; e': 8.5 +/- 2.1 vs 11.3 +/- 1.7 cm/s, p < 0.001), whereas in the LV
lateral wall only e' was lower (11.2 +/- 2.6 vs 13.8 +/- 2.3 cm/s, p < 0.001). LV
IVA was not different between the groups (p = 0.10). LV peak global longitudinal
strain was lower in HTx patients (18 +/- 1.9% vs 20 +/- 2.2%, p = 0.001), but
peak circumferential strain was not different (p = 0.50). At peak, HR was lower
in the HTx group (141 +/- 12 vs 165 +/- 15, p < 0.001), and all systolic and
diastolic parameters, except circumferential strain, were lower in HTx
recipients. When assessing the increase in TDI and strain values in relation to
HR, the slopes were not significantly different between patients and controls.
CONCLUSIONS: Despite resting differences in myocardial functional parameters,
pediatric HTx recipients have preserved LV diastolic and systolic myocardial
reserve in response to exercise.
PMID- 25130554
TI - De novo donor HLA-specific antibodies predict development of bronchiolitis
obliterans syndrome after lung transplantation.
AB - BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the major cause of late
graft failure after lung transplantation. The objective was to determine whether
de novo donor human leukocyte antigen (HLA)-specific antibodies (DSA) are
associated with the development of BOS or patient survival. Data were analyzed
from 188 lung transplant recipients with a follow-up period up to 8 years.
METHODS: HLA antibody monitoring was performed at 3-month intervals post
transplant at routine outpatient clinic attendances and during the investigation
of any acute deterioration. HLA antibody data were available for 148 patients; 66
(45%) had produced HLA antibodies after transplant, of which 38 (26%) were DSA
and 28 (19%) non-donor-specific HLA antibodies. RESULTS: De novo DSA was
associated with development of BOS Stage 1 (BOS1; hazard ratio [HR] = 2.302, p =
0.0015), BOS2 (HR = 3.627, p < 0.0001) and BOS3 (HR = 5.736, p < 0.0001). De novo
persistent DSA correlated strongly with shorter time to onset of BOS3 (HR =
6.506, p = 0.0001). There was a significant reduction in patient survival
associated with de novo DSA (HR = 1.886, p = 0.047). In multivariable analyses,
de novo DSA was an independent predictor for development of all stages of BOS as
well as an independent predictor of poor patient survival. CONCLUSIONS: De novo
DSA is a major risk factor for progression to BOS and shorter patient survival.
Treatments to remove antibodies or limit antibody-mediated damage could be
considered when DSA are first detected. However, a randomized, controlled trial
of treatment options would enable a clearer understanding of the benefits, if
any, of antibody-removal therapies.
PMID- 25130555
TI - Effect of initial surgical palliation on allosensitization and post-transplant
outcomes in infants with hypoplastic left heart syndrome.
PMID- 25130556
TI - Sulforaphane-induced autophagy flux prevents prion protein-mediated neurotoxicity
through AMPK pathway.
AB - Prion diseases are neurodegenerative and infectious disorders that involve
accumulation of misfolded scrapie prion protein, and which are characterized by
spongiform degeneration. Autophagy, a major homeostatic process responsible for
the degradation of cytoplasmic components, has garnered attention as the
potential target for neurodegenerative diseases such as prion disease. We focused
on protective effects of sulforaphane found in cruciferous vegetables on prion
mediated neurotoxicity and the mechanism of sulforaphane related to autophagy. In
human neuroblastoma cells, sulforaphane protected prion protein (PrP) (106-126)
mediated neurotoxicity and increased autophagy flux marker microtubule-associated
protein 1 light chain 3-II protein levels, following a decrease of p62 protein
level. Pharmacological and genetical inhibition of autophagy by 3MA, wortmannin
and knockdown of autophagy-related 5 (ATG5) led to block the effect of
sulforaphane against PrP (106-126)-induced neurotoxicity. Furthermore we
demonstrated that both sulforaphane-induced autophagy and protective effect of
sulforaphane against PrP (106-126)-induced neurotoxicity are dependent on the AMP
activated protein kinase (AMPK) signaling. The present results indicated that
sulforaphane of cruciferous vegetables enhanced autophagy flux led to the
protection effects against prion-mediated neurotoxicity, which was regulated by
AMPK signaling pathways in human neuron cells. Our data also suggest that
sulforaphane has a potential value as a therapeutic tool in neurodegenerative
disease including prion diseases.
PMID- 25130557
TI - Contribution of Ih to the relative facilitation of synaptic responses induced by
carbachol in the entorhinal cortex during repetitive stimulation of the
parasubiculum.
AB - Neurons in the superficial layers of the entorhinal cortex provide the
hippocampus with the majority of its cortical sensory input, and also receive the
major output projection from the parasubiculum. This puts the parasubiculum in a
position to modulate the activity of entorhinal neurons that project to the
hippocampus. These brain areas receive cholinergic projections that are active
during periods of theta- and gamma-frequency electroencephalographic (EEG)
activity. The purpose of this study was to investigate how cholinergic receptor
activation affects the strength of repetitive synaptic responses at these
frequencies in the parasubiculo-entorhinal pathway and the cellular mechanisms
involved. Whole-cell patch-clamp recordings of rat layer II medial entorhinal
neurons were conducted using an acute slice preparation, and responses to 5-pulse
trains of stimulation at theta- and gamma-frequency delivered to the
parasubiculum were recorded. The cholinergic agonist carbachol (CCh) suppressed
the amplitude of single synaptic responses, but also produced a relative
facilitation of synaptic responses evoked during stimulation trains. The N-methyl
d-aspartate (NMDA) glutamate receptor blocker APV did not significantly reduce
the relative facilitation effect. However, the hyperpolarization-activated
cationic current (Ih) channel blocker ZD7288 mimicked the relative facilitation
induced by CCh, suggesting that CCh-induced inhibition of Ih could produce the
effect by increasing dendritic input resistance (Rin). Inward-rectifying and leak
K(+) currents are known to interact with Ih to affect synaptic excitability.
Application of the K(+) channel antagonist Ba(2+) depolarized neurons and
enhanced temporal summation, but did not block further facilitation of train
evoked responses by ZD7288. The Ih-dependent facilitation of synaptic responses
can therefore occur during reductions in inward-rectifying potassium current
(IKir) associated with dendritic depolarization. Thus, in addition to cholinergic
reductions in transmitter release that are known to facilitate train-evoked
responses, these findings emphasize the role of inhibition of Ih in the
integration of synaptic inputs within the entorhinal cortex during
cholinergically-induced oscillatory states, likely due to enhanced summation of
excitatory postsynaptic potentials (EPSPs) induced by increases in dendritic Rin.
PMID- 25130558
TI - Diphenyl-diselenide suppresses amyloid-beta peptide in Caenorhabditis elegans
model of Alzheimer's disease.
AB - Alzheimer's disease (AD) is the most common and devastating neurodegenerative
disease. The etiology of AD has yet to be fully understood, and common treatments
remain largely non-efficacious. The amyloid hypothesis posits that extracellular
amyloid-beta (Abeta) deposits are the fundamental etiological factor of the
disease. The present study tested the organoselenium compound diphenyl-diselenide
(PhSe)2, which is characterized by its antioxidant and antiinflammatory
properties and has shown efficacy in several neurodegenerative disease models. We
employed a transgenic Caenorhabditis elegans AD model to analyze the effects of
(PhSe)2 treatment on Abeta peptide-induced toxicity. Chronic exposure to (PhSe)2
attenuated oxidative stress induced by Abeta1-42, with concomitant recovery of
associative learning memory in C. elegans. Additionally, (PhSe)2 decreased Abeta1
42 transgene expression, suppressed Abeta1-42 peptide, and downregulated hsp-16.2
by reducing the need for this chaperone under Abeta1-42-induced toxicity. These
observations suggest that (PhSe)2 plays an important role in protecting against
oxidative stress-induced toxicity, thus representing a promising pharmaceutical
modality that attenuates Abeta1-42 expression.
PMID- 25130560
TI - 5-HT3A receptors are required in long-term depression and AMPA receptor
internalization.
AB - 5-Hydroxytrytamine (serotonin) type 3A receptors (5-HT3ARs), as the only ligand
gated ion channels in the serotonin receptor family, are known to regulate
neuronal excitation and release of GABA in hippocampal interneurons. However,
their physiological role in glutamatergic synaptic plasticity remains unclear.
Here, we show that deletion of the 5-HT3AR gene in transgenic mice abolished N
methyl-d-aspartate (NMDA) receptor (NMDAR)-dependent long-term depression (LTD)
induced by low-frequency stimulation (LFS) in hippocampal CA1 synapses in slices,
whereas the metabotropic glutamate receptor (mGluR)-dependent LTD did not change
in the 5-HT3AR knockout mice. In addition, 5-HT3ARs disruption inhibited alpha
amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs)
internalization, without altering basal surface levels of AMPARs. However, the
deletion of 5-HT3ARs did not lead to loss of synapses and structural alteration
of dendritic spines. Furthermore, the concentrations of 5-HT and 5
hydroxyindoleacetic acid (5-HIAA) in the hippocampus were not affected by the
deletion of 5-HT3ARs. These observations revealed an important role of 5-HT3ARs
in NMDAR-dependent long-term depression, which is critical for learning
behaviors.
PMID- 25130559
TI - Downstream effects of striatal-enriched protein tyrosine phosphatase reduction on
RNA expression in vivo and in vitro.
AB - Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific
tyrosine phosphatase that has been shown to de-phosphorylate several key neuronal
signaling proteins, including kinases (extracellular signal-regulated kinase
(ERK1/2), FYN, PYK2) and glutamate receptor subunits (N-methyl-d-aspartate
receptor subtype 2B (NR2B), glutamate receptor 2 (GLUR2)). Step knock-out mice
have increased phosphorylation of these substrates in the brain, with potential
functional consequences in synaptic plasticity and cognitive tasks. It is
therefore of interest to identify the molecular pathways and downstream
transcriptional targets that are impacted by Step knockdown. In the present
study, striatal RNA samples from Step wild-type, knock-out and heterozygous mice
were hybridized to Affymetrix microarray chips and evaluated for transcriptional
changes between genotypes. Pathway analysis highlighted Erk signaling and
multiple pathways related to neurotrophin signaling, neuronal development and
synaptic transmission. Potential genes of interest identified by microarray were
confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) in the
cortex and hippocampus, which shared several transcriptional alterations with the
striatum. In order to evaluate Step knockdown in an in vitro system, a panel of
genes were evaluated using qRT-PCR in rat cortical neurons that were transduced
with lentivirus expressing short hairpin RNA against Step or a non-targeting
control. Our data suggest that Step has a role in the expression of immediate
early genes relevant to synaptic plasticity, in both in vitro and in vivo
systems.
PMID- 25130562
TI - Maternal administration of flutamide during late gestation affects the brain and
reproductive organs development in the rat male offspring.
AB - We have previously demonstrated that male rats exposed to stress during the last
week of gestation present age-specific impairments of brain development. Since
the organization of the fetal developing brain is subject to androgen exposure
and prenatal stress was reported to disrupt perinatal testosterone surges, the
aim of this research was to explore whether abnormal androgen concentrations
during late gestation affects the morphology of the prefrontal cortex (PFC),
hippocampus (HPC) and ventral tegmental area (VTA), three major areas that were
shown to be affected by prenatal stress in our previous studies. We administered
10-mg/kg/day of the androgen receptor antagonist flutamide (4'nitro-3'
trifluoromethylsobutyranilide) or vehicle injections to pregnant rats from days
15-21 of gestation. The antiandrogenic effects of flutamide were confirmed by the
analysis of androgen-dependent developmental markers: flutamide-exposed rats
showed reduced anogenital distance, delay in the completion of testis descent,
hypospadias, cryptorchidism and atrophied seminal vesicles. Brain morphological
studies revealed that prenatal flutamide decreased the number of MAP2 (a
microtubule-associated protein type 2, present almost exclusively in dendrites)
immunoreactive neuronal processes in all evaluated brain areas, both in
prepubertal and adult offspring, suggesting that prenatal androgen disruption
induces long-term reductions of the dendritic arborization of several brain
structures, affecting the normal connectivity between areas. Moreover, the number
of tyrosine hydroxylase (TH)-immunopositive neurons in the VTA of prepubertal
offspring was reduced in flutamide rats but reach normal values at adulthood. Our
results demonstrate that the effects of prenatal flutamide on the offspring brain
morphology resemble several prenatal stress effects suggesting that the mechanism
of action of prenatal stress might be related to the impairment of the
organizational role of androgens on brain development.
PMID- 25130561
TI - Age-related increases in right frontal activation during task switching are
mediated by reaction time and white matter microstructure.
AB - Age-related increases in right frontal cortex activation are a common finding in
the neuroimaging literature. However, neurocognitive factors contributing to
right frontal over-recruitment remain poorly understood. Here we investigated the
influence of age-related reaction time (RT) slowing and white matter (WM)
microstructure reductions as potential explanatory factors for age-related
increases in right frontal activation during task switching. Groups of younger
(N=32) and older (N=33) participants completed a task switching paradigm while
functional magnetic resonance imaging (fMRI) was performed, and rested while
diffusion tensor imaging (DTI) was performed. Two right frontal regions of
interest (ROIs), the dorsolateral prefrontal cortex (DLPFC) and insula, were
selected for further analyses from a common network of regions recruited by both
age groups during task switching. Results demonstrated age-related activation
increases in both ROIs. In addition, the older adult group showed longer RT and
decreased fractional anisotropy in regions of the corpus callosum with direct
connections to the fMRI ROIs. Subsequent mediation analyses indicated that age
related increases in right insula activation were mediated by RT slowing and age
related increases in right DLPFC activation were mediated by WM microstructure.
Our results suggest that age-related RT slowing and WM microstructure declines
contribute to age-related increases in right frontal activation during cognitive
task performance.
PMID- 25130564
TI - Sea surface temperature contributes to marine crocodylomorph evolution.
AB - During the Mesozoic and Cenozoic, four distinct crocodylomorph lineages colonized
the marine environment. They were conspicuously absent from high latitudes, which
in the Mesozoic were occupied by warm-blooded ichthyosaurs and plesiosaurs.
Despite a relatively well-constrained stratigraphic distribution, the varying
diversities of marine crocodylomorphs are poorly understood, because their
extinctions neither coincided with any major biological crises nor with the
advent of potential competitors. Here we test the potential link between their
evolutionary history in terms of taxic diversity and two abiotic factors, sea
level variations and sea surface temperatures (SST). Excluding Metriorhynchoidea,
which may have had a peculiar ecology, significant correlations obtained between
generic diversity and estimated Tethyan SST suggest that water temperature was a
driver of marine crocodylomorph diversity. Being most probably ectothermic
reptiles, these lineages colonized the marine realm and diversified during warm
periods, then declined or became extinct during cold intervals.
PMID- 25130565
TI - Catalytic constructive deoxygenation of lignin-derived phenols: new C-C bond
formation processes from imidazole-sulfonates and ether cleavage reactions.
AB - As part of a programme aimed at exploiting lignin as a chemical feedstock for
less oxygenated fine chemicals, several catalytic C-C bond forming reactions
utilising guaiacol imidazole sulfonate are demonstrated. These include the cross
coupling of a Grignard, a non-toxic cyanide source, a benzoxazole, and
nitromethane. A modified Meyers reaction is used to accomplish a second
constructive deoxygenation on a benzoxazole functionalised anisole.
PMID- 25130563
TI - The network property of the thalamus in the default mode network is correlated
with trait mindfulness.
AB - Mindfulness is typically defined as nonjudgmental awareness of experiences in the
present moment, which is beneficial for mental and physical well-being. Previous
studies have identified multiple regions in the default mode network (DMN) that
are involved in mindfulness, but little is known about how these regions work
collaboratively as a network. Here, we used resting-state functional magnetic
resonance imaging to investigate the role of the DMN in trait mindfulness by
correlating spontaneous functional connectivity among DMN nodes with self
reported trait mindfulness in a large population of young human adults. Among all
pairs of the DMN nodes, we found that individuals with weaker functional
connectivity between the thalamus and posterior cingulate cortex (PCC) were more
mindful of the present. Post-hoc analyses of these two nodes further revealed
that graph-based nodal properties of the thalamus, not the PCC, were negatively
correlated with trait mindfulness, suggesting that a low involvement of the
thalamus in the DMN is relevant for high trait mindfulness. Our findings not only
suggest the thalamus as a switch between mind-wandering and mindfulness, but also
invite future studies on mechanisms of how mindfulness produces beneficial
effects by modulating the thalamus.
PMID- 25130566
TI - Radiobiological modeling and the study of hypofractionated radiotherapy for
prostate cancer.
PMID- 25130567
TI - Does reduced feeding prior to release improve the marine migration of hatchery
brown trout Salmo trutta smolts?
AB - The aim of this study was to test the hypothesis that hatchery brown trout Salmo
trutta smolts, with 50% reduced or no feeding over the last 5 months before
release, were more likely to migrate to the sea than individuals with standard
feeding ratios. The juvenile fish were divided into three groups 176 days before
release: (A) with no feeding, (B) with 50% and (C) with 100% feeding. To study
their seaward migration, 40 fish from each feeding group were tagged with
acoustic transmitters and tracked by automatic listening stations in the River
Nidelva, Trondheim, Norway, its estuary and in the nearest marine environment. At
the time of release, mean condition factor was significantly lower in group A and
the fish from groups A and B had higher levels of Na+, K+-ATPase. Significantly
more fish from group A migrated to the sea, but the rate of downstream
progression from release to the estuary did not differ between the three groups.
In conclusion, the S. trutta smolts with no access to food in the last 176 day
before release were more likely to migrate to the sea. Fish from all three
feeding groups, however, appeared to smoltify and had the same rate of downstream
progression to the estuary. This indicates that differences in migratory
behaviour between individuals from the three feeding groups begin from the time
when the fish reach saline waters. It is suggested that feeding in hatcheries has
to be greatly reduced (by 50% or more) over several months to have a pronounced
effect on the migratory behaviour in S. trutta.
PMID- 25130568
TI - First-episode affective psychosis and lipid monitoring: survival analysis of the
first abnormal lipid test.
AB - AIM: This study aimed to assess the probability of developing a lipid test
abnormality over time, among first-time users of antipsychotic medications with
affective psychosis. METHODS: Survival analysis was used to analyse data from an
early intervention in psychosis programme for the first 53 consecutive and
eligible cases of patients between the ages of 14 and 40 years who had a
diagnosis of affective psychosis. Data on initiation of antipsychotic medications
and lipid laboratory test results were abstracted from chart reviews. RESULTS:
Within the first 18 months of receiving antipsychotic medications, the
probability of surviving without an abnormal lipid test was only 25% (confidence
interval 95%: 13.1%, 40.4%). The median time to the development of an abnormal
test was 8 months for males and 12 months for females (P < 0.001). CONCLUSIONS:
Additional studies are needed to document the incidence over time of abnormal
lipid tests to inform clinicians about the optimal frequency of monitoring.
PMID- 25130569
TI - Overall ED efficiency is associated with decreased time to percutaneous coronary
intervention for ST-segment elevation myocardial infarction.
AB - BACKGROUND: Performance of percutaneous coronary intervention (PCI) within 90
minutes of hospital arrival for ST-segment elevation myocardial infarction
patients is a commonly cited clinical quality measure. The Centers for Medicare
and Medicaid Services use this measure to adjust hospital reimbursement via the
Value-Based Purchasing Program. This study investigated the relationship between
hospital performance on this quality measure and emergency department (ED)
operational efficiency. METHODS: Hospital-level data from Centers for Medicare
and Medicaid Services on PCI quality measure performance was linked to
information on operational performance from 272 US EDs obtained from the
Emergency Department Benchmarking Alliance annual operations survey. Standard
metrics of ED size, acuity, and efficiency were compared across hospitals grouped
by performance on the door-to-balloon time quality measure. RESULTS: Mean
hospital performance on the 90-minute arrival to PCI measure was 94.0% (range, 42
100). Among hospitals failing to achieve the door-to-balloon time performance
standard, median ED length of stay was 209 minutes, compared with 173 minutes
among those hospitals meeting the benchmark standard (P < .001). Similarly,
median time from ED patient arrival to physician evaluation was 39 minutes for
hospitals below the performance standard and 23 minutes for hospitals at the
benchmark standard (P < .001). Markers of ED size and acuity, including annual
patient volume, admission rate, and the percentage of patients arriving via
ambulance did not vary with door-to-balloon time. CONCLUSION: Better performance
on measures associated with ED efficiency is associated with more timely PCI
performance.
PMID- 25130570
TI - Rhodium-coordinated poly(arylene-ethynylene)-alt-poly(arylene-vinylene) copolymer
acting as photocatalyst for visible-light-powered NAD+/NADH reduction.
AB - A 2,2'-bipyridyl-containing poly(arylene-ethynylene)-alt-poly(arylene-vinylene)
polymer, acting as a light-harvesting ligand system, was synthesized and coupled
to an organometallic rhodium complex designed for photocatalytic NAD(+)/NADH
reduction. The material, which absorbs over a wide spectral range, was
characterized by using various analytical techniques, confirming its chemical
structure and properties. The dielectric function of the material was determined
from spectroscopic ellipsometry measurements. Photocatalytic reduction of
nucleotide redox cofactors under visible light irradiation (390-650 nm) was
performed and is discussed in detail. The new metal-containing polymer can be
used to cover large surface areas (e.g. glass beads) and, due to this
immobilization step, can be easily separated from the reaction solution after
photolysis. Because of its high stability, the polymer-based catalyst system can
be repeatedly used under different reaction conditions for (photo)chemical
reduction of NAD(+). With this concept, enzymatic, photo-biocatalytic systems for
solar energy conversion can be facilitated, and the precious metal catalyst can
be recycled.
PMID- 25130571
TI - Randomized trial of human milk cream as a supplement to standard fortification of
an exclusive human milk-based diet in infants 750-1250 g birth weight.
AB - OBJECTIVE: To evaluate whether premature infants who received an exclusive human
milk (HM)-based diet and a HM-derived cream supplement (cream) would have weight
gain (g/kg/d) at least as good as infants receiving a standard feeding regimen
(control). STUDY DESIGN: In a prospective noninferiority, randomized, unmasked
study, infants with a birth weight 750-1250 g were randomly assigned to the
control or cream group. The control group received mother's own milk or donor HM
with donor HM-derived fortifier. The cream group received a HM-derived cream
supplement if the energy density of the HM tested <20 kcal/oz using a near
infrared HM analyzer. Infants were continued on the protocol until 36 weeks
postmenstrual age. Primary outcomes included growth velocities and amount of
donor HM-derived fortifier used. The hypothesis of noninferiority was established
if the lower bound of the one-sided 95% CI for the difference in weight
velocities exceeded -3 g/kg/day. RESULTS: There were no differences between
groups in baseline demographics for the 78 infants studied except racial
distribution (P = .02). The cream group (n = 39) had superior weight (14.0 +/-
2.5 vs 12.4 +/- 3.0 g/kg/d, P = .03) and length (1.03 +/- 0.33 vs 0.83 +/- 0.41
cm/wk, P = .02) velocity compared with the control group (n = 39). There were no
significant differences in amount of fortifier used between study groups. The 1
sided 95% lower bound of the CI for the difference in mean velocity (cream
control) was 0.38 g/kg/d. CONCLUSIONS: Premature infants who received HM-derived
cream to fortified HM had improved weight and length velocity compared with the
control group. HM-derived cream should be considered an adjunctive supplement to
an exclusive HM-based diet to improve growth rates in premature infants.
PMID- 25130573
TI - Cultural adaptation of preschool PATHS (Promoting Alternative Thinking
Strategies) curriculum for Pakistani children.
AB - Cultural adaptation of evidence-based programmes has gained importance primarily
owing to its perceived impact on the established effectiveness of a programme. To
date, many researchers have proposed different frameworks for systematic
adaptation process. This article presents the cultural adaptation of preschool
Promoting Alternative Thinking Strategies (PATHS) curriculum for Pakistani
children using the heuristic framework of adaptation (Barrera & Castro, 2006).
The study was completed in four steps: information gathering, preliminary
adaptation design, preliminary adaptation test and adaptation refinement.
Feedbacks on programme content suggested universality of the core programme
components. Suggested changes were mostly surface structure: language,
presentation of materials, conceptual equivalence of concepts, training needs of
implementation staff and frequency of programme delivery. In-depth analysis was
done to acquire cultural equivalence. Pilot testing of the outcome measures
showed strong internal consistency. The results were further discussed with
reference to similar work undertaken in other cultures.
PMID- 25130572
TI - An automated system using spatial oversampling for optical mapping in murine
atria. Development and validation with monophasic and transmembrane action
potentials.
AB - We developed and validated a new optical mapping system for quantification of
electrical activation and repolarisation in murine atria. The system makes use of
a novel 2nd generation complementary metal-oxide-semiconductor (CMOS) camera with
deliberate oversampling to allow both assessment of electrical activation with
high spatial and temporal resolution (128 * 2048 pixels) and reliable assessment
of atrial murine repolarisation using post-processing of signals. Optical
recordings were taken from isolated, superfused and electrically stimulated
murine left atria. The system reliably describes activation sequences, identifies
areas of functional block, and allows quantification of conduction velocities and
vectors. Furthermore, the system records murine atrial action potentials with
comparable duration to both monophasic and transmembrane action potentials in
murine atria.
PMID- 25130574
TI - JSAP1 and JLP are required for ARF6 localization to the midbody in cytokinesis.
AB - The ADP-ribosylation factor 6 (ARF6) GTPase is important in cytokinesis and
localizes to the midbody. However, the mechanism and regulation of ARF6's
recruitment to the midbody are largely unknown. Here, we investigated the
functions of two binding partners of active ARF6, c-Jun NH2 -terminal kinase
(JNK)/stress-activated protein kinase-associated protein 1 (JSAP1) and JNK
associated leucine zipper protein (JLP), by gene knockout and rescue experiments
in mouse embryonic fibroblasts. Depleting both JSAP1 and JLP impaired ARF6's
localization to the midbody and delayed cytokinesis. These defects were almost
completely rescued by wild-type JSAP1 or JLP, but not by JSAP1 or JLP mutants
that were unable to interact with active ARF6 or with the kinesin heavy chain
(KHC) of kinesin-1. In transfected cells, a constitutively active form of ARF6
associated with KHC only when co-expressed with wild-type JSAP1 or JLP and not
with a JSAP1 or JLP mutant. These findings suggest that JSAP1 and JLP, which
might be paralogous to each other, are critical and functionally redundant in
cytokinesis and control ARF6 localization to the midbody by forming a tripartite
complex of JSAP1/JLP, active ARF6, and kinesin-1.
PMID- 25130576
TI - A possible means of countering the underdiagnosis of Klinefelter Syndrome.
PMID- 25130578
TI - New insights into SET protein during mouse spermatogenesis.
PMID- 25130577
TI - Testicular parenchymal abnormalities in Klinefelter syndrome: a question of
cancer? Examination of 40 consecutive patients.
AB - Klinefelter syndrome (KS) is a hypergonadotropic hypogonadism characterized by a
47, XXY karyotype. The risk of testicular cancer in KS is of interest in relation
to theories about testicular cancer etiology generally; nevertheless it seems to
be low. We evaluated the need for imaging and serum tumor markers for testicular
cancer screening in KS. Participants were 40 consecutive KS patients, enrolled
from December 2009 to January 2013. Lactate dehydrogenase (LDH), alpha
fetoprotein (AFP), and beta-human chorionic gonadotrophin subunit (beta-HCG)
serum levels assays and testicular ultrasound (US) with color Doppler, were
carried out at study entry, after 6 months and every year for 3 years. Abdominal
magnetic resonance (MR) was performed in KS when testicular US showed micro
calcifications, testicular nodules and cysts. Nearly 62% of the KS had regular
testicular echotexture, 37.5% showed an irregular echotexture and 17.5% had micro
calcifications and cysts. Eighty seven percent of KS had a regular vascular
pattern, 12.5% varicocele, 12.5% nodules <1 cm, but none had nodules >1 cm. MR
ruled out the diagnosis of cancer in all KS with testicular micro calcifications,
nodules and cysts. No significant variations in LDH, AFP, and beta-HCG levels and
in US pattern have been detected during follow-up. We compared serum tumor
markers and US pattern between KS with and without cryptorchidism and no
statistical differences were found. We did not find testicular cancer in KS, and
testicular US, tumor markers and MR were, in selected cases, useful tools for
correctly discriminating benign from malignant lesions.
PMID- 25130580
TI - Bacteria and the prostate: infertility versus symptoms.
PMID- 25130581
TI - Glucocorticoid metabolism in testicular tissue: a key to fertility?
PMID- 25130582
TI - Complex and time-consuming laboratory modifications are not always necessary to
improve outcome.
PMID- 25130583
TI - The impact of male overweight on semen quality and outcome of assisted
reproduction.
PMID- 25130584
TI - Prevention of erectile dysfunction after radiotherapy for prostate cancer.
AB - With increasing scrutiny of prostate cancer (PCa) diagnosis and treatment, much
attention has been given to the morbidity caused by radical prostatectomy (RP)
and/or radiotherapy (RT). One of the most common side-effects of either treatment
is erectile dysfunction (ED). Approximately, 40% of patients will experience ED
after RT for PCa. The post-RT ED causes significant patient dissatisfaction with
cancer treatment as well as decrease in patient and partner psychosocial
function. To address this issue in patients undergoing RT, Pisansky et al.
conducted a prospective, randomized, double-blinded, placebo-controlled trial to
assess the efficacy of a phosphodiesterase enzyme-5 inhibitor (PDE5i), tadalafil,
as a preventive measure for patients undergoing RT for PCa and found no
difference in erectile function between the control and treatment groups.
PMID- 25130585
TI - Circumcision standards: can we improve further?
PMID- 25130586
TI - Male patients with terminal renal failure exhibit low serum levels of
antimullerian hormone.
AB - Male reproductive function is impaired during end-stage renal disease (ESRD).
Disturbance of the hypothalamic-pituitary-gonadal axis, and therefore the
regulation of sex hormones, is one of the major causes. Our focus was to include
antimullerian hormone (AMH) and inhibin B concentrations. Twenty male patients on
hemodialysis, median age 40 (26-48) years, were analyzed for follicle-stimulating
hormone (FSH), luteinizing hormone (LH), prolactin, sex hormone-binding globulin
(SHBG), testosterone, estradiol, AMH and inhibin B levels. We used 144 proven
fertile men, median age 32 (19-44) years as a control group and analyzed
differences using multiple linear regression. Males with ESRD demonstrated higher
mean values for prolactin, 742 versus normal 210 mIE l-1 (95% confidence interval
(CI): 60.3, 729), LH, 8.87 versus normal 4.5 IE l-1 (95% CI: 2.75, 6.14), and
estradiol 89.7 versus normal 79.0 pmol l-1 (95% CI: -1.31, -0.15). Mean value for
AMH was lower, 19.5 versus normal 47.3 pmol l-1 (95% CI: -37.6, -11.6). There
were no differences found for FSH, SHBG, inhibin B and testosterone. The most
important difference was found for AMH, a marker of Sertoli cell function in the
testes, which decreased by close to 60% when compared with controls. Combined
with an increase in LH, these findings may indicate a dysfunction of Sertoli
cells and an effect on Leydig cells contributing to a potential mechanism of
reproductive dysfunction in men with ESRD.
PMID- 25130587
TI - Region 2 of 8q24 is associated with the risk of aggressive prostate cancer in
Caribbean men of African descent from Guadeloupe (French West Indies).
AB - Multiple regions of the genome have been associated with the risk of prostate
cancer in Caucasians, particularly including several polymorphisms located at
8q24. Region 2 of 8q24 has been repeatedly found to be associated with the risk
of prostate cancer among men of African descent, although one study performed in
the Caribbean island of Jamaica did not report this finding. In this study, the
single nucleotide polymorphism rs16901979, located in region 2 of 8q24, was
genotyped in 498 cases of histologically confirmed prostate cancer and 541
controls from the French Caribbean islands of Guadeloupe, where the population is
largely of African descent. The AA genotype and the A allele at rs16901979 were
associated with elevated risks of prostate cancer (odds ratios [ORs] = 1.84, 95%
confidence interval [95% CI] = 1.26-2.69, P = 0.002 and OR = 1.36, 95% CI = 1.13
1.64, P = 0.001, respectively). Following stratification of the patients by
disease aggressiveness, as defined by the Gleason score, the pooled genotypes AC
+ AA were associated with a higher risk of a Gleason score >=7 at diagnosis (OR =
1.79, 95% CI = 1.17-2.73, P = 0.007). In summary, the A allele at rs16901979 was
associated with the risk of prostate cancer in the Caribbean population of
Guadeloupe, confirming its involvement in populations of African descent.
Moreover, our study provides the first evidence of an association between this
variant and the risk of aggressive prostate cancer.
PMID- 25130589
TI - Stress modulation of cellular metabolic sensors: interaction of stress from
temperature and rainfall on the intertidal limpet Cellana toreuma.
AB - In the natural environment, organisms are exposed to large variations in physical
conditions. Quantifying such physiological responses is, however, often performed
in laboratory acclimation studies, in which usually only a single factor is
varied. In contrast, field acclimatization may expose organisms to concurrent
changes in several environmental variables. The interactions of these factors may
have strong effects on organismal function. In particular, rare events that occur
stochastically and have relatively short duration may have strong effects. The
present experiments studied levels of expression of several genes associated with
cellular stress and metabolic regulation in a field population of limpet Cellana
toreuma that encountered a wide range of temperatures plus periodic rain events.
Physiological responses to these variable conditions were quantified by measuring
levels of mRNA of genes encoding heat-shock proteins (Hsps) and metabolic sensors
(AMPKs and Sirtuin 1). Our results reveal high ratios of individuals in
upregulation group of stress-related gene expression at high temperature and
rainy days, indicating the occurrence of stress from both prevailing high summer
temperatures and occasional rainfall during periods of emersion. At high
temperature, stress due to exposure to rainfall may be more challenging than heat
stress alone. The highly variable physiological performances of limpets in their
natural habitats indicate the possible differences in capability for
physiological regulation among individuals. Our results emphasize the importance
of studies of field acclimatization in unravelling the effects of environmental
change on organisms, notably in the context of multiple changes in abiotic
factors that are accompanying global change.
PMID- 25130588
TI - Nematode resistance to ivermectin (630 and 700MUg/kg) in cattle from the
Southeast and South of Brazil.
AB - Two high doses of ivermectin (630MUg/kg and 700MUg/kg) that are sold commercially
in Brazil were evaluated in dose-and-slaughter trials with 144 naturally nematode
infected cattle from eight regions within the states of Minas Gerias, Sao Paulo
and Rio Grande do Sul in Brazil. Treatment groups were based on fecal egg counts
1, 2, and 3days before treatment; all animals studied had a minimum egg count of
at least 500 eggs per gram of feces (EPG). Post-mortem analyses were conducted on
day 14. The highest levels of resistance to ivermectin were found for Haemonchus
placei, Cooperia punctata and Oesophagostomum radiatum; all populations of H.
placei were resistant to the 630MUg/kg dose, and 67% were resistant to 700MUg/kg;
86% of C. punctata were resistant to the 630MUg/kg dose, and 33% were resistant
to 700MUg/kg. A combined analysis revealed that 57% of O. radiatum were resistant
to the lower dose of ivermectin. H. placei, C. punctata and O. radiatum, in
order, were the nematode populations with the highest indices of resistance,
whereas Trichostrongylus axei was the most susceptible to 630 and 700MUg/kg
dosages of ivermectin. The results of helminthic resistance to ivermectin for
different populations of H. placei and C. punctata described in the present study
support previous literature data, in which a small decrease in the average
parasitic burden of C. punctata and a consequent increase of H. placei were
observed in cattle from the Southeast, South and Center-West regions of Brazil.
PMID- 25130591
TI - Dominant components of the Thoroughbred metabolome characterised by (1) H-nuclear
magnetic resonance spectroscopy: A metabolite atlas of common biofluids.
AB - REASONS FOR PERFORMING STUDY: Metabonomics is emerging as a powerful tool for
disease screening and investigating mammalian metabolism. This study aims to
create a metabolic framework by producing a preliminary reference guide for the
normal equine metabolic milieu. OBJECTIVES: To metabolically profile plasma,
urine and faecal water from healthy racehorses using high resolution (1) H
nuclear magnetic resonance (NMR) spectroscopy and to provide a list of dominant
metabolites present in each biofluid for the benefit of future research in this
area. STUDY DESIGN: This study was performed using 7 Thoroughbreds in race
training at a single time point. Urine and faecal samples were collected
noninvasively and plasma was obtained from samples taken for routine clinical
chemistry purposes. METHODS: Biofluids were analysed using (1) H-NMR
spectroscopy. Metabolite assignment was achieved via a range of one- and 2
dimensional experiments. RESULTS: A total of 102 metabolites were assigned across
the 3 biological matrices. A core metabonome of 14 metabolites was ubiquitous
across all biofluids. All biological matrices provided a unique window on
different aspects of systematic metabolism. Urine was the most populated
metabolite matrix with 65 identified metabolites, 39 of which were unique to this
biological compartment. A number of these were related to gut microbial host
cometabolism. Faecal samples were the most metabolically variable between
animals; acetate was responsible for the majority (28%) of this variation. Short
chain fatty acids were the predominant features identified within this biofluid
by (1) H-NMR spectroscopy. CONCLUSIONS: Metabonomics provides a platform for
investigating complex and dynamic interactions between the host and its
consortium of gut microbes and has the potential to uncover markers for health
and disease in a variety of biofluids. Inherent variation in faecal extracts
along with the relative abundance of microbial-mammalian metabolites in urine and
invasive nature of plasma sampling, infers that urine is the most appropriate
biofluid for the purposes of metabonomic analysis.
PMID- 25130592
TI - Does Synergy Exist in Nursing? A Concept Analysis.
AB - AIM: The aim is to analyze the concept of synergy, particularly as the concept
applies to teamwork, and determine if the concept has utility in improving the
work environment for nurses. Tackling nursing shortages that result from a poor
work environment is a priority for many nurse leaders. Producing synergy among
teams may be an effective strategy in enhancing the work environment. However,
the understanding of synergy and the ability to produce synergy among teams has
been seldom highlighted or discussed within nursing literature. Walker and
Avant's approach was used to guide this concept analysis of synergy. SOURCES:
Literature searches involved databases (PsycInfo, Medline, Cumulative Index for
Nursing and Allied Health Literature [CINAHL], and Scopus), Internet search
engines (Google), and hand searches. CONCLUSION: The analysis suggests that
synergy is an outcome of the successful collaboration of the following three
attributes: group cohesion, the pursuit of a common goal, and the achievement of
a positive gain, considerably more than what was thought possible by the group.
The foundation for this accomplishment requires an underlying feeling of special
importance, the acknowledgment of each member's role, and open communication and
dialogue among members. Nursing leaders would benefit from a broader
understanding of synergy, and the mindful application and utility of synergy as
an outcome of effective teamwork among nurses.
PMID- 25130590
TI - Histone acetylation in the nucleus accumbens shell modulates ethanol-induced
locomotor activity in DBA/2J mice.
AB - BACKGROUND: A growing body of literature suggests that epigenetic mechanisms,
including histone acetylation, may play key roles in drug abuse and the
development of addiction. Experiments in this study were designed to investigate
the role of histone acetylation in ethanol (EtOH)-induced locomotor
sensitization. METHODS: Immunohistochemical, Western blotting, and site-directed
pharmacological techniques were used to explore the roles of histone acetylation
at histone H3 (acH3K9) in both the expression of and acquisition of EtOH-induced
locomotor sensitization. A commonly used sensitization protocol, in which animals
were exposed to repeated injections of a low dose of EtOH while in their home
cage, was used to examine this behavioral phenomenon. Additionally, site-directed
administration of the histone deacetylase inhibitor (HDACi) Trichostatin A (TSA),
in the absence of repeated EtOH injections, was used to examine the role of
hyperacetylation in the nucleus accumbens (NAC) shell in EtOH-induced locomotor
sensitization. RESULTS: Sensitized mice displayed elevated acH3K9
immunoreactivity (IR) localized to the shell of the NAC. This augmentation in
acH3K9 IR was confirmed, in a separate experiment, using Western blot analyses.
Next, repeated intra-accumbal infusions of TSA, in the absence of repeated EtOH
injections, were sufficient to induce an augmented locomotor response to a later
injection of a low dose (2.0 g/kg, intraperitoneally) of EtOH, indicative of
cross-sensitization to this locomotor stimulation between TSA and EtOH. Finally,
a local infusion of TSA into the shell of the accumbens was also associated with
a significant increase in acH3K9 IR within this region. CONCLUSIONS: Together,
the present observations suggest that histone acetylation, particularly within
the shell of the NAC, is important for the development and expression of EtOH
induced locomotor sensitization.
PMID- 25130594
TI - Benzodithiophene based pi-conjugated macrocycles: synthesis, morphology and
electrochemical characterization.
AB - A 7,8-didodecyloxybenzo[1,2-b:4,3-b']dithiophene (BdT-Dod) containing a
macrocycle was synthesized from a thiophene capped BdT-Dod comonomer through a
Ti(iv) mediated McMurry reaction and characterized by (1)H NMR, (13)C NMR and
MALDI-TOF mass spectrometry. Additionally, the morphological characterization was
performed by AFM and SEM to investigate the self-aggregation properties. The
macrocycle underwent self-assembly in the solid state to form fibers on the
Si/SiO2 surface with a length in the MUm range and a thickness of about 400 nm.
PMID- 25130593
TI - Clinical performance of the Prostate Health Index (PHI) for the prediction of
prostate cancer in obese men: data from the PROMEtheuS project, a multicentre
European prospective study.
AB - OBJECTIVES: To test serum prostate-specific antigen (PSA) isoform [-2]proPSA
(p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in
predicting prostate cancer in obese men and to test whether PHI is more accurate
than PSA in predicting prostate cancer in obese patients. PATIENTS AND METHODS:
The analysis consisted of a nested case-control study from the pro-PSA
Multicentric European Study (PROMEtheuS) project. The study is registered at
http://www.controlled-trials.com/ISRCTN04707454. The primary outcome was to test
sensitivity, specificity and accuracy (clinical validity) of serum p2PSA, %p2PSA
and PHI, in determining prostate cancer at prostate biopsy in obese men [body
mass index (BMI) >=30 kg/m(2) ], compared with total PSA (tPSA), free PSA (fPSA)
and fPSA/tPSA ratio (%fPSA). The number of avoidable prostate biopsies (clinical
utility) was also assessed. Multivariable logistic regression models were
complemented by predictive accuracy analysis and decision-curve analysis.
RESULTS: Of the 965 patients, 383 (39.7%) were normal weight (BMI <25 kg/m(2) ),
440 (45.6%) were overweight (BMI 25-29.9 kg/m(2) ) and 142 (14.7%) were obese
(BMI >=30 kg/m(2) ). Among obese patients, prostate cancer was found in 65
patients (45.8%), with a higher percentage of Gleason score >=7 diseases (67.7%).
PSA, p2PSA, %p2PSA and PHI were significantly higher, and %fPSA significantly
lower in patients with prostate cancer (P < 0.001). In multivariable logistic
regression models, PHI significantly increased accuracy of the base multivariable
model by 8.8% (P = 0.007). At a PHI threshold of 35.7, 46 (32.4%) biopsies could
have been avoided. CONCLUSION: In obese patients, PHI is significantly more
accurate than current tests in predicting prostate cancer.
PMID- 25130595
TI - The birth of an infant decreases group spacing in a zoo-housed lowland gorilla
group (Gorilla gorilla gorilla).
AB - Changes in group composition can alter the behavior of social animals such as
gorillas. Although gorilla births are presumed to affect group spacing patterns,
there is relatively little data about how these events affect gorilla group
cohesion. We investigated how members of a western lowland gorilla group (n = 6)
at Lincoln Park Zoo (Chicago, IL, USA) spaced themselves prior to and after the
birth of an infant, to investigate changes in group cohesion. Gorillas were
housed in an indoor-outdoor enclosure in which access to the outdoors was
permitted when temperatures exceeded 5 degrees C. We recorded spatial locations
of each group member using 30-min group scans on tablet computers with an
electronic map interface, as well as noting their access to outdoor areas. Data
from the 4 months following the birth was compared to a control period
corresponding to early pregnancy. We measured distances between all possible
group dyads for each scan and subsequently calculated a mean distance between all
group members. An ANOVA revealed that access to the outdoors had no effect on
group spacing (F(1,56) = 0.066, P = 0.799). However, the presence of an infant
resulted in a significant reduction in inter-individual distance (F(1,56) =
23.988, P = 0.000), decreasing inter-individual spacing by 12.5%. This
information helps characterize the behavioral impact of a new birth on captive
gorilla social structure and could potentially inform future management of
breeding gorilla groups.
PMID- 25130596
TI - Social participation and health-related quality of life in people with multiple
sclerosis.
AB - BACKGROUND: Social participation is an integral part of everyday life in society;
however, evidence about its association with health-related quality of life
(HRQoL) in people with multiple sclerosis (MS) is lacking. OBJECTIVE: The aim of
this study is to explore whether social participation is associated with the
Physical Component Summary of HRQoL (PCS) and Mental Component Summary of HRQoL
(MCS) in people with MS, controlled for age, gender, disease severity and disease
duration. METHODS: The sample consisted of 116 consecutive people with MS
(response rate: 75.8%; 72.4% women; mean age 40.3 +/- 9.8). People with MS
completed the Short-Form Health Survey (SF-36) for measuring PCS and MCS and the
Participation Scale, which measures the level of social participation. Disability
was assessed using the Expanded Disability Status Scale (EDSS). The associations
between social participation, PCS and MCS, were analyzed using linear regression
that controlled for sociodemographic and clinical variables. RESULTS: PCS was
significantly associated with age, disease duration, EDSS and social
participation. MCS did not show significant association with the studied
variables. Overall, a multiple regression model explained 48% of the PCS
variance, while the proportion of MCS variance explained was not significant.
CONCLUSIONS: Social participation was significantly associated with PCS,
suggesting a possibility for intervention in this domain.
PMID- 25130597
TI - A nationwide population-based cohort study on tonsillectomy and subsequent cancer
incidence.
AB - OBJECTIVES/HYPOTHESIS: Tonsillectomy is related to increased risk of certain
types of cancer. This study evaluates the possible association between
tonsillectomy and cancer in Taiwan. METHODS: Data from the National Health
Insurance system of Taiwan was used. A cohort study consisting of 997 patients
with a new diagnosis of tonsillectomy from 2000 to 2005 and a comparison cohort
of 3,988 subjects without tonsillectomy were used in the Poisson regression
analysis to estimate the incidence rate ratios (IRRs) and 95% confidence
intervals (CIs) of cancers. RESULTS: The incidence rate of all cancer types was
higher in the tonsillectomy group than in the control group (4.28 vs. 2.97 per
1,000 person-years, respectively), with an IRR = 1.54 and 95% CI of 1.05 to 2.25,
but the significant difference was limited to patients with more than 3 years
follow-up. Site-specific analysis found no significant association between
tonsillectomy and any individual cancer after adjusting for age, sex,
hyperlipidemia, hypertension, and diabetes; however, tonsillectomy patients with
more than 3 years follow-up had a marginally significantly higher risk for breast
cancer development (adjusted IRR = 2.62; CI = 0.97-7.03). CONCLUSION: Our study
found that Taiwanese people with tonsillectomy have a significantly higher
overall risk of developing cancer and a marginally higher risk of developing
breast cancer when follow-up is longer than 3 years.
PMID- 25130598
TI - Nursing educators' perceptions about disaster preparedness and response in
Istanbul and Miyazaki.
AB - AIM: As healthcare professionals, nursing educators need to be prepared to manage
and deliver care in what are often dangerous conditions. This research aims to
determine and compare nursing educators' perceptions of disaster preparedness and
response (DP&R) in Istanbul and Miyazaki. METHODS: An 18 question descriptive
questionnaire was used. RESULTS: One hundred and forty-four nursing educators
representing two state university nursing schools in Istanbul, Turkey, and one
state and two private universities in Miyazaki, Japan were enrolled. Educators
had an average age of 40 years and had been educators for 1-15 years. Just over
half of the participants had basic knowledge regarding DP&R with most of them
considering taking special courses in the future. The majority considered
"caregiver" as a role they could undertake in a disaster situation. The existence
of major concerns and conflicts in disaster responses were low. The top ranked
item was in the area of conflict between family and job responsibilities. Age and
academic levels showed significant differences in basic knowledge on DP&R.
Regardless of knowledge in this subject area, no statistical significance on
personal preparedness or being a volunteer to disaster events was found.
CONCLUSION: Nursing educators were not thinking about what kinds of disasters
occur in the areas where they currently teach and were underprepared to deal with
disaster situations. To improve the perceptions of the nursing educators on DP&R,
mass casualty care and disaster management skills need to be incorporated into
formal education and training on disaster preparedness and workplace
preparedness.
PMID- 25130599
TI - A general overview of the organocatalytic intramolecular aza-Michael reaction.
AB - The organocatalytic intramolecular aza-Michael reaction gives access to
enantiomerically enriched nitrogen-containing heterocycles in a very simple
manner. Enals, enones, conjugated esters and nitro olefins have been employed as
Michael acceptors, while moderate nitrogen nucleophiles such as sulphonamides,
carbamates and amides have been shown to be appropriate Michael donors in this
type of reaction. Additionally, the process has been performed under both
covalent and non-covalent catalysis, with diaryl prolinols, imidazolidinones,
thioureas and chiral binol phosphoric acids being the most frequently used
catalysts. The level of efficiency reached with this protocol is demonstrated by
the implementation of numerous tandem processes, as well as the total synthesis
of several natural products.
PMID- 25130600
TI - Fabrication of ultralong hybrid microfibers from nanosheets of reduced graphene
oxide and transition-metal dichalcogenides and their application as
supercapacitors.
AB - Two-dimensional materials have attracted increasing research interest owing to
their unique electronic, physical, optical, and mechanical properties. We thus
developed a general strategy for the fabrication of ultralong hybrid microfibers
from a mixture of reduced graphene oxide and transition-metal dichalcogenides
(TMDs), including MoS2 , TiS2 , TaS2 , and NbSe2 . Furthermore, we prepared fiber
based solid-state supercapacitors as a proof-of-concept application. The
performance of thus-prepared supercapacitors was greatly improved by the
introduction of the TMDs.
PMID- 25130601
TI - Molecular pathology in lung cancer: a guide to the techniques used in clinical
practice.
AB - Five year survival rates for lung cancer patients are poor; however the
development of new therapeutic options, which benefit subsets of the population,
offer hope of improvement. These novel therapies frequently rely upon the
analysis of biomarkers in pathology samples; in lung cancer patients, testing is
now routinely carried out to identify small mutations and chromosomal
rearrangements in order to predict response to treatment. The recent increase in
biomarker analyses in pathology samples has lead to the development of a new
specialty, molecular pathology. The use of molecular pathology assays in clinical
samples is largely under the control of the histopathologist; who is likely to be
asked, as a minimum, to select tissue sections for molecular analysis and mark
areas of H&E stained slides for macro or microdissection. Many histopathologists
will also be involved in the sourcing and implementation of new assays. This
review aims to provide a guide to some of the most commonly used molecular
pathology methods - their advantages and their limitations.
PMID- 25130603
TI - The STRONGkids nutritional risk screening tool can be used by paediatric nurses
to identify hospitalised children at risk.
AB - AIM: Hospitalised children have higher rates of undernutrition. Early detection
of at-risk patients could lead to prompt preventative or corrective
interventions. Several nutritional risk screening tools are available for
screening hospitalised children including the STRONGkids tool. This study was
designed to assess the usefulness of STRONGkids when applied by nurses rather
than a paediatrician. METHODS: The STRONGkids questionnaire was simplified to
enhance clarity with nursing staff. Trained nursing staff were asked to apply the
tool to children, aged 1 month to 17 years, admitted to the Christchurch
Hospital, New Zealand. Each patient was also assessed by a paediatrician. In
addition, the current nutritional state of each patient was defined by measuring
their weight and height. RESULTS: Of the 162 children enrolled, 11.7% were
undernourished and 13% overnourished. STRONGkids recognised 84% of undernourished
children when the tool was applied by nurses and 90% when the tool was applied by
a paediatrician, indicating substantial agreement (kappa = 0.65). A minor
simplification to the questionnaire improved its utility. CONCLUSION: STRONGkids
successfully recognised at-risk children, when applied by either nurses or a
paediatrician. It was suitable and feasible for nursing staff to use it to screen
for children at risk of nutritional deterioration.
PMID- 25130602
TI - Risk factors for major adverse events late after Fontan palliation.
AB - OBJECTIVE: Risk factors for major adverse events late after Fontan palliation are
unknown. Prior studies have suggested ventricular function and morphology as
important risk factors. The aim of this study is to (1) characterize the late
major adverse event profile in adult Fontan patients and (2) identify additional
risk factors that may contribute to adverse outcomes. DESIGN AND SETTING: A
retrospective review of all adult patients >15 years post-Fontan seen at a
tertiary academic center was conducted. Clinical, laboratory, cardiac data, and
abdominal imaging were collected via chart review. Major adverse events (death,
cardiac transplantation, or listing) were identified, and timing of events was
plotted using Kaplan-Meier methods. Univariate and multivariate logistic
regression was used to determine independent predictors of late-term events.
RESULTS: A total of 123 adult Fontan patients were identified (mean time post
Fontan 22.4 years [+/-4.4]). Major adverse events occurred in 19/123 patients
(15%). In this 15-year survivor cohort, transplant-free survival rates were
94.6%, 82.9%, and 59.8% at 20, 25, and 30 years postoperation, respectively.
Modes of death were Fontan failure with preserved function (4), congestive heart
failure with decreased function (2), sudden death (2), thromboembolic event (1),
post-Fontan conversion (2), and posttransplant (2). No differences in adverse
outcomes were found based on morphology of the systemic ventricle, Fontan type,
or systolic ventricular function. On the other hand, features of portal
hypertension (OR 19.0, CI 4.7-77.3, P < .0001), presence of a pacemaker (OR 13.4,
CI 2.6-69.8, P = .002), and systemic oxygen desaturation (OR 0.86, CI 0.75-0.98,
P = .02) were risk factors for major adverse events in the multivariate analysis.
CONCLUSIONS: In adult Fontan patients surviving >15 years post-Fontan, portal
hypertension, oxygen desaturation, and need for pacemaker were predictive of
adverse events. Traditional measures may not predict late-term outcomes in adult
survivors; further study of the liver's role in late outcomes is warranted.
PMID- 25130604
TI - Aptamers as drug delivery vehicles.
AB - The benefits of directed and selective therapy for systemic treatment are reasons
for increased interest in exploiting aptamers for cell-specific drug delivery.
Nucleic acid based pharmaceuticals represent an interesting and novel tool to
counter human diseases. Combining inhibitory potential and cargo transfer upon
internalization, nanocarriers as well as various therapeutics including siRNAs,
chemotherapeutics, photosensitizers, or proteins can be imported via these
synthetic nucleic acids. However, widespread clinical application is still
hampered by obstacles that must be overcome. In this review, we give an overview
of applications and recent advances in aptamer-mediated drug delivery. We also
introduce prominent selection methods as well as useful approaches in choice of
drug and conjugation method. We discuss the challenges that need to be considered
and present strategies that have been applied to achieve intracellular delivery
of effectors transported by readily internalized aptamers.
PMID- 25130605
TI - Predonation screening of candidate donors and prevention of window period
donations.
AB - BACKGROUND: Infectious window period donations slip through routine donor
screening procedures. To explore the potential value of predonation screening of
candidate donors, we compared the proportion of incident transfusion
transmissible infections in candidate donors, in first-time donors, and in repeat
donors. STUDY DESIGN AND METHODS: A retrospective analysis was performed of all
incident hepatitis B virus (HBV), hepatitis C virus (HCV), and human
immunodeficiency virus (HIV) infections in candidate, first-time, and repeat
donors in the Netherlands during the period 2009 to 2013. RESULTS: In total,
176,716 candidate donors, 144,226 first-time donations, and 4,143,455 repeat
donations were screened for HBV, HCV, and HIV infection. Acute HBV infection was
identified in the predonation sample of six candidate donors. One first-time
donor, testing HIV-negative at predonation screening, tested positive for anti
HIV and HIV RNA in the first donation 29 days later. Among repeat donations we
identified 15, one, and six incident HBV, HCV and HIV infections, respectively.
The proportion of incident infections among candidate donors/first-time
donations/repeat donations was for HBV, 3.40/0/0.36; for HCV, 0/0/0.02; and for
HIV 0/0.69/0.14 per 100,000, respectively. CONCLUSION: Predonation screening of
candidate donors very likely causes a loss of donations, but it might prevent
undetected window period donations. Further studies are necessary to determine
the value of predonation screening as an additional safety measure.
PMID- 25130606
TI - THP-1 cell line: an in vitro cell model for immune modulation approach.
AB - THP-1 is a human leukemia monocytic cell line, which has been extensively used to
study monocyte/macrophage functions, mechanisms, signaling pathways, and nutrient
and drug transport. This cell line has become a common model to estimate
modulation of monocyte and macrophage activities. This review attempts to
summarize and discuss recent publications related to the THP-1 cell model. An
overview on the biological similarities and dissimilarities between the THP-1
cell line and human peripheral blood mononuclear cell (PBMC) derived-monocytes
and macrophages, as well as the advantages and disadvantages of the use of THP-1
cell line, is included. The review summarizes different published co-cultivation
studies of THP-1 cells with other cell types, for instance, intestinal cells,
adipocytes, T-lymphocytes, platelets, and vascular smooth muscle cells, which can
be an option to study cell-cell interaction in vitro and can be an approach to
better mimic in vivo conditions. Macrophage polarization is a relatively new
topic which gains interest for which the THP-1 cell line also may be relevant.
Besides that an overview of newly released commercial THP-1 engineered-reporter
cells and THP-1 inflammasome test-cells is also given. Evaluation of recent
papers leads to the conclusion that the THP-1 cell line has unique
characteristics as a model to investigate/estimate immune-modulating effects of
compounds in both activated and resting conditions of the cells. Although the THP
1 response can hint to potential responses that might occur ex vivo or in vivo,
these should be, however, validated by in vivo studies to draw more definite
conclusions.
PMID- 25130607
TI - Prolonged pretreatment of mice with cholera toxin, but not isoproterenol,
alleviates acute lethal systemic inflammatory response.
AB - Isoproterenol, a synthetic non-selective beta-adrenergic agonist, is often used
during the immediate postoperative period after open heart surgery for its
chronotropic and vasodilatory effects. It has been demonstrated that
isoproterenol pretreatment followed by immediate LPS administration leads to
reduced tumor necrosis factor-alpha (TNF-alpha) response in vivo. However, sepsis
never happens immediately after the surgery, but rather severe immune dysfunction
occurs at least 24h later. It remains elusive what effects isoproterenol might
exert to innate immunity during the period. In this scenario, we investigated the
effects of 24-h isoproterenol pretreatment on septic shock induced by
experimental endotoxemia and bacterial peritonitis, with cholera toxin as another
cAMP elevator. Unexpectedly, we found that isoproterenol and cholera toxin
exhibited distinct effects in acute lethal systemic inflammatory response.
Isoproterenol worsened liver injury without enhancing NK/NKT activity. Meanwhile,
cholera toxin but not isoproterenol showed dramatically reduced TNF-alpha
response in LPS induced septic shock. Our data provide a caution for the clinical
use of isoproterenol and suggest that isoproterenol has cAMP-independent
functions.
PMID- 25130608
TI - All trans-retinoic acid abrogates the pro-tumorigenic phenotype of prostate
cancer tumor-associated macrophages.
AB - Tumor-associated macrophages (TAMs) are a prominent cell type of the tumor stroma
and stimulate malignant cell growth, survival and metastasis. The present
manuscript demonstrates that prostate cancer cell-derived factors induce a pro
tumoral TAM-like phenotype characterized by increased proliferation and increased
expression of pro-angiogenic, immunosuppressive and pro-metastatic factors. These
effects were abrogated by all trans-retinoic acid (ATRA), a clinically available
molecule with known immune-modulating properties. Furthermore, ATRA inhibited the
cancer cell-stimulated proliferation of the pro-tumoral macrophages and restored
their cytotoxic capacity towards prostate cancer cells. These findings suggest
the use of ATRA as an immunomodulating agent to block the activity of prostate
cancer TAMs.
PMID- 25130610
TI - Shared genetic risk factors for psychiatric illness.
PMID- 25130609
TI - "Celtic migrations": fact or fiction? Strontium and oxygen isotope analysis of
the Czech cemeteries of Radovesice and Kutna Hora in Bohemia.
AB - Strontium and oxygen isotope analysis of human remains from the early La Tene
(fourth/third century BC) Czech cemeteries of Radovesice I (RAD I), Radovesice II
(RAD II), and Kutna Hora were conducted to investigate the importance of
residential changes during the period of the historic "Celtic migrations". In the
initial phases (LT A/B), the grave goods of these cemeteries are typical for the
core area of the La Tene culture, while around 300 BC (LT B2) an alteration
occurs and typical Bohemian styles arise, and connections to Moravia and the
Danubian region become visible. The strontium isotope ratios are highly varied
with (87) Sr/(86) Sr values between 0.7062 and 0.7153 in Radovesice, and between
0.7082 and 0.7147 in Kutna Hora. The oxygen isotope data are more homogeneous and
yield delta(18) Op ratios from 14.80/00 to 17.20/00 [mean: 16.20/00 +/- 0.5
(1sigma)] in Radovesice, and from 14.90/00 to 17.30/00 [mean: 16.50/00 +/- 0.6
(1sigma)] in Kutna Hora. Because the geological properties of the landscapes
around the sites are variable and complex, most of the observed variations among
the strontium isotope ratios may have been caused by agricultural practices, such
as regularly changing farming land. Nevertheless, there are some individuals who
differ completely from the regional isotopic baseline values. This suggests that
at least a small part of the community migrated, which does not seem to be
correlated with any particular phase of the La Tene period. Remarkably, it is
mainly males who seem to be of nonlocal origin, and particularly those who were
buried as warriors. Females, on the other hand, appear to have been more closely
bonded to the Bohemian region. Whether the "foreign" individuals with differing
isotopic compositions came from Moravia or the Danubian region remains debatable.
PMID- 25130611
TI - Der p 2 can induce bystander activation of B cells derived from patients with
systemic lupus erythematosus.
AB - Although many patients with SLE also have allergies, the immunological events
triggering the onset and progression of the clinical manifestations of SLE by
allergens have yet to be clarified. A total of three autoantigens,
phosphoglycerate kinase 1 (PGK-1), triosephosphate isomerase (TIM) and enolase
were identified by autologous serum in B cell lysate derived from HDM allergic
SLE patients after Der p 2 stimulation. Autoantigen, TRIM-21 expression were also
significantly increased in B cells derived from HDM allergic SLE patients. In
PBMCs derived from SLE patients, the concentration of anti-PGK-1 was
significantly upregulated after Der p 2 stimulation compared to HDM allergic
without SLE patients and healthy subjects. Inflammatory related cytokines and
chemokines include IL-1beta, IL-6, IL-8, CXCL5 could be upregulated after Der p 2
stimulation in PBMCs derived from HDM allergic SLE patients. In conclusion, our
data demonstrated that long-term allergen exposure could be a contributing factor
in the development of SLE.
PMID- 25130612
TI - Efficacy analysis of tyrosine kinase inhibitors on rare non-small cell lung
cancer patients harboring complex EGFR mutations.
AB - The efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR
TKI) in patients with non-small cell lung cancer (NSCLC) is related to EGFR
mutations. Although the p.L858R point mutation in exon 21 and the in-frame
deletion mutation in exon 19 are well known, efficacy of EGFR-TKI in patients
with more than one EGFR mutation is not well understood. 799 NSCLC patients were
screened for EGFR mutations. Of the 799 patients, 443 (55.4%) had mutations, out
of which 22 (2.75%) had multiple complex mutations. Most multiple mutations
(20/22) harbored common mutations such as the p.L858R point mutation in exon 21
and the in-frame deletion mutation in exon 19. 11 out of 22 patients who had
multiple EGFR mutations underwent TKI therapy and primary end-points of
progression free and overall survival were determined. Our analysis revealed that
cases with multiple mutations had similar end-point outcomes as single mutation
to TKI therapy. Report of these cases will be helpful in decision making for
treatment of NSCLC patients harboring multiple EGFR mutations.
PMID- 25130613
TI - Carbamylation of immunoglobulin abrogates activation of the classical complement
pathway.
AB - Post-translational modifications of proteins significantly affect their structure
and function. The carbamylation of positively charged lysine residues to form
neutral homoitrulline occurs primarily under inflammatory conditions through
myeloperoxidase-dependent cyanate (CNO-) formation. We analyzed the pattern of
human IgG1 carbamylation under inflammatory conditions and the effects that this
modification has on the ability of antibodies to trigger complement activation
via the classical pathway. We found that the lysine residues of IgG1 are rapidly
modified after brief exposure to CNO- . Interestingly, modifications were not
random, but instead limited to only few lysines within the hinge area and the N
terminal fragment of the CH2 domain. A complement activation assay combined with
mass spectrometry analysis revealed a highly significant inverse correlation
between carbamylation of several key lysine residues within the hinge region and
N-terminus of the CH2 domain and the proper binding of C1q to human IgG1 followed
by subsequent complement activation. This severely hindered complement-dependent
cytotoxicity of therapeutic IgG1 . The reaction can apparently occur in vivo, as
we found carbamylated antibodies in synovial fluid from rheumatoid arthritis
patients. Taken together, our data suggest that carbamylation has a profound
impact on the complement-activating ability of IgG1 and reveals a pivotal role
for previously uncharacterized lysine residues in this process.
PMID- 25130614
TI - Mutation of Dcdc2 in mice leads to impairments in auditory processing and memory
ability.
AB - Dyslexia is a complex neurodevelopmental disorder characterized by impaired
reading ability despite normal intellect, and is associated with specific
difficulties in phonological and rapid auditory processing (RAP), visual
attention and working memory. Genetic variants in Doublecortin domain-containing
protein 2 (DCDC2) have been associated with dyslexia, impairments in phonological
processing and in short-term/working memory. The purpose of this study was to
determine whether sensory and behavioral impairments can result directly from
mutation of the Dcdc2 gene in mice. Several behavioral tasks, including a
modified pre-pulse inhibition paradigm (to examine auditory processing), a 4/8
radial arm maze (to assess/dissociate working vs. reference memory) and rotarod
(to examine sensorimotor ability and motor learning), were used to assess the
effects of Dcdc2 mutation. Behavioral results revealed deficits in RAP, working
memory and reference memory in Dcdc2(del2/del2) mice when compared with matched
wild types. Current findings parallel clinical research linking genetic variants
of DCDC2 with specific impairments of phonological processing and memory ability.
PMID- 25130616
TI - Soil as a source of Legionella pneumophila sequence type 47.
AB - Legionella pneumophila sequence type (ST) 47 was isolated from soil in a garden.
We speculate that this strain was transmitted from soil to the whirlpool in the
garden where it caused an outbreak of Legionnaires' disease and Pontiac fever. In
the Netherlands, ST47 is frequently isolated from patients, but hardly ever from
environmental sources. It is possible that human pathogenic Legionella strains,
with ST47 as one of the predominant strains, are transmitted to humans from
sources such as natural soil that are currently not targeted in outbreak
investigations.
PMID- 25130615
TI - Bone regeneration with osteogenically enhanced mesenchymal stem cells and their
extracellular matrix proteins.
AB - Although bone has remarkable regenerative capacity, about 10% of long bone
fractures and 25% to 40% of vertebral fusion procedures fail to heal. In such
instances, a scaffold is employed to bridge the lesion and accommodate
osteoprogenitors. Although synthetic bone scaffolds mimic some of the
characteristics of bone matrix, their effectiveness can vary because of
biological incompatibility. Herein, we demonstrate that a composite prepared with
osteogenically enhanced mesenchymal stem cells (OEhMSCs) and their extracellular
matrix (ECM) has an unprecedented capacity for the repair of critical-sized
defects of murine femora. Furthermore, OEhMSCs do not cause lymphocyte
activation, and ECM/OEhMSC composites retain their in vivo efficacy after
cryopreservation. Finally, we show that attachment to the ECM by OEhMSCs
stimulates the production of osteogenic and angiogenic factors. These data
demonstrate that composites of OEhMSCs and their ECM could be utilized in the
place of autologous bone graft for complex orthopedic reconstructions.
PMID- 25130617
TI - Efficacy of real-time polymerase chain reaction for rapid diagnosis of
endobronchial tuberculosis.
AB - OBJECTIVES: The definitive diagnosis of endobronchial tuberculosis (EBTB) is
challenging because the disease manifests in various non-specific ways, and acid
fast bacilli (AFB) are often undetectable by sputum smear. The objective of this
study was to evaluate the efficacy of real-time PCR of bronchoscopic biopsy
specimens for the diagnosis of EBTB. METHODS: Real-time PCR amplification of
Mycobacterium tuberculosis DNA in biopsy tissue from EBTB patients was performed
prospectively. Diagnostic yields were compared for real-time PCR and for auramine
O-stained sputum smears and bronchial brush smears. Whether diagnostic yield
depended on bronchoscopic subtype of EBTB was also evaluated. RESULTS: Diagnostic
yields were 4.1% (3/74) for sputum smear, 39.2% (29/74) for bronchial brush
smear, and 89.2% (66/74) for real-time PCR. Real-time PCR melting curve analysis
showed significantly higher yields than did AFB staining of bronchial brush
smears for granular and caseating EBTB (p<0.01). CONCLUSIONS: Real-time PCR
detection of M. tuberculosis DNA in EBTB biopsy tissue is more sensitive than
sputum smear and bronchial brush smear, including at early disease stages. This
PCR method may be a useful adjunct to culture- and smear-based techniques to
allow more rapid EBTB diagnosis and timelier treatment.
PMID- 25130618
TI - Xylan-mediated aggregation of Lactobacillus brevis and its relationship with the
surface properties and mucin-mediated aggregation of the bacteria.
AB - Some Lactobacillus brevis strains were found to aggregate upon the addition of
xylan after screening for lactic acid bacteria that interact with plant
materials. The S-layer proteins of cell surface varied among the strains. The
strains that displayed xylan-mediated aggregation retained its ability even after
the removal of S-layer proteins. L. brevis had negative zeta potentials. A
correlation between the strength of aggregation and zeta potential was not
observed. However, partial removal of S-layer proteins resulted in decreases in
the electric potential and aggregation ability of some strains. Therefore, xylan
mediated aggregation of L. brevis was considered to be caused by an electrostatic
effect between the cells and xylan. L. brevis also aggregated in the presence of
mucin, and the strengths of aggregation among the strains were similar to that
induced by xylan. Thus, xylan- and mucin-mediated L. brevis aggregation was
supposed to be caused by a similar mechanism.
PMID- 25130619
TI - Calculating core-level excitations and X-ray absorption spectra of medium-sized
closed-shell molecules with the algebraic-diagrammatic construction scheme for
the polarization propagator.
AB - Core-level excitations are generated by absorption of high-energy radiation such
as X-rays. To describe these energetically high-lying excited states
theoretically, we have implemented a variant of the algebraic-diagrammatic
construction scheme of second-order ADC(2) by applying the core-valence
separation (CVS) approximation to the ADC(2) working equations. Besides
excitation energies, the CVS-ADC(2) method also provides access to properties of
core-excited states, thereby allowing for the calculation of X-ray absorption
spectra. To demonstrate the potential of our implementation of CVS-ADC(2), we
have chosen medium-sized molecules as examples that have either biological
importance or find application in organic electronics. The calculated results of
CVS-ADC(2) are compared with standard TD-DFT/B3LYP values and experimental data.
In particular, the extended variant, CVS-ADC(2)-x, provides the most accurate
results, and the agreement between the calculated values and experiment is
remarkable.
PMID- 25130620
TI - Alpine climate treatment of atopic dermatitis: a systematic review.
AB - Climate therapy has been used for decades in the treatment of atopic dermatitis
(AD), but evidence of its effectiveness has not yet been assessed systematically.
A systematic literature search in Medline, Embase, and the Cochrane library was
performed to identify all original studies concerning alpine climate treatment.
The risk of bias of individual studies was assessed following the Cochrane
Handbook, and level of evidence was rated using GRADE guidelines. Fifteen
observational studies were included concerning 40 148 patients. Four studies
concerning 2670 patients presented follow-up data over a period of 1 year.
Disease activity decreased in the majority of patients during treatment (96% of n
= 39 006) and 12-month follow-up (64% of n = 2670). Topical corticosteroid use
could often be reduced or stopped during treatment (82% of n = 1178) and during
12-month follow-up (72% of n = 3008). Quality assessment showed serious study
limitations, therefore resulting in a very low level of evidence for the
described outcomes. Randomized controlled trials designed with a follow-up period
including well-defined patient populations, detailed description and measurement
of applied interventions during climate therapy and using validated outcomes
including cost-effectiveness parameters, are required to improve the evidence for
alpine climate therapy as an effective treatment for patients with AD.
PMID- 25130621
TI - Blockade of monoacylglycerol lipase inhibits oligodendrocyte excitotoxicity and
prevents demyelination in vivo.
AB - The endocannabinoids 2-araquidonoylglycerol (2-AG) and anandamide (AEA) are
bioactive lipids crucially involved in the regulation of brain function in basal
and pathological conditions. Blockade of endocannabinoid metabolism has emerged
as a promising therapeutic strategy for inflammatory diseases of the central
nervous system, including myelin disorders such as multiple sclerosis.
Nevertheless, the biological actions of endocannabinoid degradation inhibitors in
oligodendrocytes and white matter tracts are still ill defined. Here we show that
the selective monoacylglycerol lipase (MAGL) inhibitor JZL184 suppressed cell
death by mild activation of AMPA receptors in oligodendrocytes in vitro, an
effect that was mimicked by MAGL substrate 2-AG and by the second major
endocannabinoid AEA, in a concentration-dependent manner, whereas inhibition of
the AEA metabolizing enzyme fatty acid amide hydrolase with URB597 was devoid of
effect. Pharmacological experiments suggested that oligodendrocyte protection
from excitotoxicity resulting from MAGL blockade involved the activation of
cannabinoid CB1 receptors and the reduction of AMPA-induced cytosolic calcium
overload, mitochondrial membrane depolarization, and production of reactive
oxygen species. Administration of JZL184 under a therapeutic regimen decreased
clinical severity, prevented demyelination, and reduced inflammation in chronic
experimental autoimmune encephalomyelitis. Furthermore, MAGL inactivation
robustly preserved myelin integrity and suppressed microglial activation in the
cuprizone-induced model of T-cell-independent demyelination. These findings
suggest that MAGL blockade may be a useful strategy for the treatment of immune
dependent and -independent damage to the white matter.
PMID- 25130622
TI - Supine or sitting? Economic considerations regarding patient position during
plasma metanephrine analysis for the exclusion of chromaffin tumours.
PMID- 25130623
TI - Improving acid-fast fluorescent staining for the detection of mycobacteria using
a new nucleic acid staining approach.
AB - Acid fast staining of sputum smears by microscopy remains the prevalent method
for detecting Mycobacterium tuberculosis. The sensitivity of microscopy using
acid fast stains requires 10(4) bacilli per ml of sputum. Although fluorescent
acid fast stains, such as Auramine-O, show improved sensitivity, almost half of
culture-positive TB cases are currently estimated to remain smear-negative. These
current diagnosis problems provide impetus for improving staining procedures. We
evaluated a novel fluorescent acid-fast staining approach using the nucleic acid
binding dye SYBR((r)) Gold on mycobacterial in vitro cultures. The SYBR((r)) Gold
stain detected 99% of MTB in both actively replicating aerobic and non
replicating hypoxic cultures. Transmission light microscopy with Ziehl-Neelsen
fuchsin, and fluorescence microscopy with Auramine-O or Auramine-rhodamine
detected only 54%-86% of MTB bacilli. SYBR((r)) Gold fluoresces more intensely
than Auramine-O, and is highly resistant to fading. The signal to noise ratio is
exceptionally high due to a >1000-fold enhanced fluorescence after binding to
DNA/RNA, thereby reducing most background fluorescence. Although cost and
stability of the dye may perhaps limit its clinical use at this time, these
results warrant further research into more nucleic acid dye variants. In the
meantime, SYBR((r)) Gold staining shows great promise for use in numerous
research applications.
PMID- 25130624
TI - Biogeochemical environments of streambed-sediment pore waters with and without
arsenic enrichment in a sedimentary rock terrain, New Jersey Piedmont, USA.
AB - Release of arsenic (As) from sedimentary rocks has resulted in contamination of
groundwater in aquifers of the New Jersey Piedmont Physiographic Province, USA;
the contamination also may affect the quality of the region's streamwater to
which groundwater discharges. Biogeochemical mechanisms involved in the release
process were investigated in the streambeds of Six Mile Run and Pike Run,
tributaries to the Millstone River in the Piedmont. At Six Mile Run, streambed
pore water and shallow groundwater were low or depleted in oxygen, and contained
As at concentrations greater than 20 MUg/L. At Pike Run, oxidizing conditions
were present in the streambed, and the As concentration in pore water was 2.1
MUg/L. The 16S rRNA gene and the As(V) respiratory reductase gene, arrA, were
amplified from DNA extracted from streambed pore water at both sites and
analyzed, revealing that distinct bacterial communities that corresponded to the
redox conditions were present at each site. Anaerobic enrichment cultures were
inoculated with pore water from gaining reaches of the streams with acetate and
As(V). As(V) was reduced by microbes to As(III) in enrichments with Six Mile Run
pore water and groundwater, whereas no reduction occurred in enrichments with
Pike Run pore water. Cloning and sequencing of the arrA gene indicated 8 unique
operational taxonomic units (OTUs) at Six Mile Run and 11 unique OTUs at Pike
Run, which may be representative of the arsenite oxidase gene arxA. Low-oxygen
conditions at Six Mile Run have favored microbial As reduction and release,
whereas release was inhibited by oxidizing conditions at Pike Run.
PMID- 25130625
TI - Comparison of three pesticide fate models with respect to the leaching of two
herbicides under field conditions in an irrigated maize cropping system.
AB - The ability of three models (PEARL, MACRO and PRZM) to describe the water
transfer and leaching of the herbicides S-metolachlor and mesotrione as observed
in an irrigated maize monoculture system in Toulouse area (France) was compared.
The models were parameterized with field, laboratory and literature data, and
pedotransfer functions using equivalent parameterization to better compare the
results and the performance of the models. The models were evaluated and compared
from soil water pressure, water content and temperature data monitored at 0.2,
0.5 and 1 m depth, together with water percolates and herbicide concentrations
measured in a tension plate lysimeter at 1 m depth. Some hydraulic (n, theta(s))
parameters and mesotrione DT50 needed calibration. After calibration, the
comparison of the results obtained by the three models indicated that PRZM was
not able to simulate properly the water dynamic in the soil profile. On the
contrary, PEARL and MACRO simulated generally quite well the observed water
pressure head and volumetric water content at the three different depths during
wetting periods (e.g. irrigated cropping period) while a poorest performance was
obtained for drying periods (fallow period with bare soil and beginning of crop
period). Similar water flow dynamics were simulated by PEARL and MACRO in the
soil profile although in general, and due to a higher evapotranspiration in
MACRO, PEARL simulated a wetter soil than MACRO. For the whole simulated period,
the performance of all models to simulate water leaching at 1m depth was poor,
with an overestimation of the total water volume measured in the lysimeter
(ranging from 2.2 to 6.6 times). By contrast, soil temperature was properly
reproduced by the three models. The models were able to simulate the leaching of
herbicides at 1m depth in similar appearance time and order of magnitude as field
observations. Cumulative observed and simulated mesotrione losses by leaching
were consistently higher than the observed and simulated losses of the less
mobile herbicide, S-metolachlor. In general, PRZM predicted the highest
concentrations for both herbicides in the leachates while PEARL simulated the
observed herbicide concentrations better than MACRO and PRZM.
PMID- 25130626
TI - Over the sands and far away: interpreting an Iberian mitochondrial lineage with
ancient Western African origins.
AB - OBJECTIVES: There is an ongoing effort to characterize the genetic links between
Africa and Europe, mostly using lineages and haplotypes that are specific to one
continent but had an ancient origin in the other. Mitochondrial DNA has been
proven to be a very useful tool for this purpose since a high number of
putatively European-specific variants of the African L* lineages have been
defined over the years. Due to their geographic locations, Spain and Portugal
seem to be ideal places for searching for these lineages. METHODS: Five members
of a minor branch of haplogroup L3f were found in recent DNA samplings in the
region of Asturias (Northern Spain), which is known for its historical isolation.
The frequency of L3f in this population (~1%) is unexpectedly high in comparison
with other related lineages in Europe. Complete mitochondrial DNA sequencing of
these L3f lineages, as well phylogenetic and phylogeographic comparative analyses
have been performed. RESULTS: The L3f variant found in Asturias seems to
constitute an Iberian-specific haplogroup, distantly related to lineages in
Northern Africa and with a deep ancestry in Western Africa. Coalescent algorithms
estimate the minimum arrival time as 8,000 years ago, and a possible route
through the Gibraltar Strait. CONCLUSIONS: Results are concordant with a
previously proposed Neolithic connection between Southern Europe and Western
Africa, which might be key to the proper understanding of the ancient links
between these two continents.
PMID- 25130627
TI - The mitochondrial genome of Paragyrodactylus variegatus (Platyhelminthes:
Monogenea): differences in major non-coding region and gene order compared to
Gyrodactylus.
AB - BACKGROUND: Paragyrodactylus Gvosdev and Martechov, 1953, a viviparous genus of
ectoparasite within the Gyrodactylidae, contains three nominal species all of
which infect Asian river loaches. The group is suspected to be a basal lineage
within Gyrodactylus Nordmann, 1832 sensu lato although this remains unclear.
Further molecular study, beyond characterization of the standard Internal
Transcribed Spacer region, is needed to clarify the evolutionary relationships
within the family and the placement of this genus. METHODS: The mitochondrial
genome of Paragyrodactylus variegatus You, King, Ye and Cone, 2014 was amplified
in six parts from a single worm, sequenced using primer walking, annotated and
analyzed using bioinformatic tools. RESULTS: The mitochondrial genome of P.
variegatus is 14,517 bp, containing 12 protein-coding genes (PCGs), 22 transfer
RNA (tRNA) genes, two ribosomal RNA (rRNA) genes and a major non-coding region
(NCR). The overall A + T content of the mitochondrial genome is 76.3%, which is
higher than all reported mitochondrial genomes of monogeneans. All of the 22
tRNAs have the typical cloverleaf secondary structure, except tRNACys, tRNASer1
and tRNASer2 that lack the dihydrouridine (DHU) arm. There are six domains
(domain III is absent) and three domains in the inferred secondary structures of
the large ribosomal subunit (rrnL) and small ribosomal subunit (rrnS),
respectively. The NCR includes six 40 bp tandem repeat units and has the double
identical poly-T stretches, stem-loop structure and some surrounding structure
elements. The gene order (tRNAGln, tRNAMet and NCR) differs in arrangement
compared to the mitochondrial genomes reported from Gyrodactylus spp. CONCLUSION:
The Duplication and Random Loss Model and Recombination Model together are the
most plausible explanations for the variation in gene order. Both morphological
characters and characteristics of the mitochondrial genome support
Paragyrodactylus as a distinct genus from Gyrodactylus. Considering their
specific distribution and known hosts, we believe that Paragyrodactylus is a
relict freshwater lineage of viviparous monogenean isolated in the high plateaus
of central Asia on closely related river loaches.
PMID- 25130628
TI - Marked Elevation of Excitatory Amino Acids in Cerebrospinal Fluid Obtained From
Patients With Rotavirus-Associated Encephalopathy.
AB - Rotavirus is the most common cause of severe gastroenteritis in young children;
however, its pathogenesis and immunity are not completely understood. Even less
well recognized is rotavirus-induced central nervous system (CNS) involvement,
which has been associated with seizure, encephalopathy and death, among others.
To elucidate the host response to rotavirus infection, we retrospectively
examined neurotransmitter amino acids in the cerebrospinal fluid (CSF) of 19
children with CNS involvement associated with rotavirus infection. Subjects were
classified into two groups: those with encephalopathy followed by prolonged
seizure (encephalopathy group) and those who had experienced afebrile, brief
cluster of seizures without encephalopathy (cluster group). The levels of
glutamate, glycine, and taurine in the encephalopathy group were significantly
higher than those in the cluster group. Increased levels of excitatory amino
acids in the CSF may induce neurological disorders and be related to disorder
severity. To the best of our knowledge, this is the first report regarding amino
acids in the CSF obtained from patients with rotavirus-induced CNS involvement.
Further study is necessary to elucidate the role of CSF amino acid levels in
rotavirus-induced CNS involvement.
PMID- 25130629
TI - [Effect of the liquid milk nutritional supplement with enhanced content of whey
protein on the nutritional status of the elderly].
AB - AIM: The aim of this study was to evaluate the effect of long-term administration
of liquid nutritional supplement with increased amounts of whey protein and
reduced amounts of lactose, produced in accordance with a new recipe "Nutrisen"
on the elderly living in institutionalized care. METHODS: The study was carried
out from May to July, 2013, on 47 retirement home residents, living in Prague,
all of which were 65 years or older. Supplemented group (n = 23) consumed (200
ml) milk drinks with three different flavours on a daily basis for eight weeks.
The reference group was on a normal diet. There was no significant difference in
baseline characteristics between participants in both groups. Anthropometric and
biochemical indicators of nutritional status and tolerance of the nutritional
supplement during long-term use were evaluated. RESULTS: Both compliance (daily
intake program) and tolerance of the nutritionally defined supplement were very
good. For the supplemented group, there was an average weight increased of 700
grams after the 8 week nutritional supplement test period. Average levels of
albumin and prealbumin increased significantly (from the beginning to the end of
the program), 35.5 +/- 4.52 g/l vs 36.19 +/- 4.1 g/l and 0.160 +/- 0.05 vs 0.174
+/- 0.04 g/l (p < 0.05), vitamin D levels increased from 31.2 +/- 16.4 nmol/l to
36.8 +/- 17.7 nmol/l (p < 0.001) and HDL-cholesterol levels increased from 1.29
+/- 0.33 mmol/l to 1.35 +/- 0.35 mmol/l (p < 0.001). CONCLUSION: The specific
nutritionally defined milk drink (Nutrisen), used in this study, was well
tolerated by the elderly study participants, over the eight-week clinical study.
We observed a positive effect on the participants weight, serum albumin,
prealbumin, vitamin D and HDL-cholesterol.
PMID- 25130630
TI - [Celiac disease in adult patients with type 1 diabetes mellitus].
AB - OBJECTIVE: To assess the prevalence of celiac disease in adult patients with type
1 diabetes mellitus (T1DM). Influence the new started treatment of celiac disease
on glycemic control and body mass index (BMI) of the patients. Prevail the anti
transglutaminase antibody (atTG) positivity one year after commencement of the
therapy. METHODS: A retrospective assessment of celiac disease targeted screening
in 465 adult T1DM patients at Diabetes Center, 1st Medical Department, University
Hospital in Pilsen (80 % of all T1DM patients) from 1. 1. 2007 until 1. 7. 2011.
Enterobiopsy was indicated in case of atTG-A (or atTG-G) positivity. In patients
with newly started gluten-free diet, HbA1c and BMI within a year after diagnosis
of celiac disease were compared to a year period six months after treatment
commencement (3-4 visits), atTG was evaluated one year after treatment beginning.
Paired T-test was used for statistical evaluation. RESULTS: The prevalence of all
forms of celiac disease in the studied group was 10.5 %. Celiac disease diagnosed
in childhood was found in 1.1 % patients (5/465). Positivity of atTG was newly
observed in 9.5 % (44/465) patients. Three patients with atTG > 300 kIU/l refused
the enterobiopsy examination. Celiac disease is highly plausible. The influence
of gluten-free diet on BMI and HbA1c could not be evaluated due to the lack of
compliance. 22 patients had a potential form of celiac disease (negative
histology). Positive enterobiopsy was found in 19 patients (4.1 %). Another 3
patients had to be excluded from the subgroup of 22 patients (newly indicated
gluten-free diet) as the HbA1c values and BMI were affected by the primary
diagnosis of T1DM. Subgroup characteristics: 9 women and 7 men, mean age 38 +/-
12 years, diabetes duration 21 +/- 13 years, celiac disease diagnosed 20.7 +/- 13
years since first diagnosis of T1DM. No statistically significant change in HbA1c
(67 +/- 11.4 vs 69 +/- 13.9 mmol/mol) was observed in the studied period, however
and a significant change of BMI from 25.4 +/- 4.2 to 25.9 +/- 4.3 (p < 0.01) was
found. The atTG positivity prevailed in 47 % (9/19) of patients after one year.
CONCLUSION: A total prevalence of the celiac disease in the group of adult T1DM
patients was 10.5 %. No significant change in HbA1c occurred following treatment,
a significant change of BMI was observed. The atTG positivity prevailed in 47 %
of patients after one year.
PMID- 25130632
TI - [Genetics and pharmacogenetics of osteoporosis].
AB - Osteoporosis is a serious disease characterized by high morbidity and mortality
due to atraumatic fractures. In pathogenesis of osteoporosis, except environment,
internal factors, such as hormonal dysbalance and genetic background, are also in
play. In this review, candidate genes for osteoporosis are classified according
to metabolic or hormonal pathways, which regulate bone mineral density/and or
quality (estrogen, RANKL/RANK/OPG, mevalonate, Wnt circuit, genes for collagen
and vitamin D). Authors discuss the perspectives of practical utilization of
pharmacogenetics (identification of single candidate genes using PCR) or
pharmacogenomics (using genome wide association studies) in choice of optimal
treatment of osteoporosis. Potentional predictors of effectivity of
antiresorption therapy are genes ER, FDPS, Cyp19A1, VDR, Col1A1 and gene of Wnt
pathway. Moreover, polymorphisms of CYP2C gene, but also FDPS may identify
patients with high risk of undesirable effects of bisphosphonates (osteonecrosis
of jaw). Unfortunately, results of the most association studies has not been
confirmed by other investigators. The controversial results could be explained by
different methodic approaches in individual studies (different sample size,
homogenity of investigated groups, ethnic differences or linkage disquilibrium
between genes). Key cliff of association studies is low variability (7-10 %) of
bone phenotypes associated with investigated genes. Nevertheless, identification
of new genes and verification their association with bone density and/or quality
using both PCR and genome wide association studies remain to be a great challenge
targeting optimal prevention and treatment of osteoporosis.
PMID- 25130631
TI - [Acute pancreatitis - validation of revised Atlanta classification on 159
patients and prognostic factors].
AB - INTRODUCTION: In the last few years the Atlanta classification of acute
pancreatitis (AP) have been revised. However prognostic markers of AP are still
being searched for. The aim of this study is to validate the 3 severity
categories proposed by the revised Atlanta classification. We also tried to
reevaluate the association between two laboratory markers (leucocyte count and
RDW - red cell distribution width) on admission and prognosis of the patients
with AP. METHODS: 159 patients were included into the study. The patients were
classified according to revised Atlanta criteria and the subgroups evaluated
according to mortality, length of hospital stay and need for interventions.
Leucocyte count and RDW on admission was evaluated in the patients. RESULTS: All
the subgroups of patients were associated with significantly relevant differences
in mortality, length of hospital stay and need for operations on pancreas.
Leucocyte count and RDW were identified as significant predictors for severe AP
and RDW was also identified as significant predictor for mortality in patients
with AP. CONCLUSION: New categories of severity as defined by Revised Atlanta
classification are describing well the mortality, length of hospital stay and
need for interventions in the patients with AP. Leucocyte count and RDW on
admission are needed to be confirmed as potential prognostic markers of severity
and mortality in AP.
PMID- 25130633
TI - [Importance of lymphangiogenesis and ultrastructure of lymphatic capillaries in
metastasis of malignant melanoma].
AB - Lymphangiogenesis - proliferation of lymphatic capillaries - in melanoma and in
its vicinity plays an important role in metastatic process of malign melanoma
cells in organism. Melanoma produces epidermal growth factor EGF which induces
vascular endothelial growth factor VEGF-C and thereby starts lymphangiogenesis.
It is very probable that malignant melanoma cells enter lymphatic capillaries
also through specialized inter-endothelial junctions (endothelial microvalves,
primary valves) situated in their walls. After entry of malign cells into
lymphatic capillaries, these cells travel in lymph to the sentinel lymph node.
Malign cells metastasize through lymphatic vessels probably also directly into
distal regional lymphatic nodes. Metastasizing through blood vessels is
suggestible also in early stage melanoma.
PMID- 25130634
TI - [What is new in heart failure with preserved ejection fraction within last five
years?].
AB - Heart failure with preserved ejection fraction of left ventricle (heart failure
with normal ejection fraction, HFPEF, HFNEF) is frequent disease with serious
consequences. Incidence of HFPEF in population is still growing. The exact
pathophysiological mechanism of HFPEF remain unclear .Recent evidence suggests a
relationship between inflammation associated with obesity or Diabetes mellitus
and progression of HFPEF. Consistently, it has been reported that serum
concentration of some pro-inflammatory markers such as adiponectin is positively
related to HFPEF. By HFPEF is attended diastolic dysfunction. Diastolic
dysfunction is linked to many other cardiac and non-cardiac diseases. Despite the
great effort and new therapeutic approaches the prognosis of HFPEF does not
improve. The gold standard in HFPEF diagnosis remains heart catheterization.
Electrocardiography, chest X-ray, blood examination including diagnostic markers
of heart failure and mainly echocardiography with Doppler imaging are used
diagnose the underlying disease leading to heart failure.
PMID- 25130636
TI - [Osteoporosis and bone alterations in celiac disease in adults].
AB - Both celiac disease and osteoporosis are common diseases which are considered an
emerging problem in medicine. Celiac disease is a condition at high risk for
secondary osteoporosis. Osteoporosis or osteopenia are typically present in
untreated adult symptomatic celiac disease with an overt malabsorption syndrome,
but is found in about 50 % in suboptimally treated celiac patients, subclinical
patients and asymptomatic adult celiac patients, too. Etiology of pathologic bone
alteration in celiac disease is multifactorial; however, two main mechanisms are
involved: intestinal malabsorption and chronic inflammation. The evaluation of
bone mineral metabolism (total calcium/albumin, 25-OH vitamin D3 and parathormone
levels in serum) and bone mineral density (densitometry) is recommended in the
clinical management of celiac patients. Many studies have demonstrated that bone
mineral density values in adults show a good improvement in the first period
after the institution of gluten-free diet, the improvement is then unsatisfactory
and treatment with a mineral-active drug should probably be considered.
PMID- 25130637
TI - [Education model at the Clinic of Internal Medicine of the Faculty Hospital Motol
Prague - our experience with local education project for young physicians on
postgraduate education].
AB - In 2004 the principal legislative changes were accepted in the field of
postgraduate medical education in Czech Republic (law No. 95/2004 Code).
Replacement of two-stage system of specialized education by its one- stage option
has brought some problems and according to our opinion did not lead to clear
improvement of postgraduate education, more likely the other way around. Our
effort to improve the quality of process of postgraduate specialization in
internal medicine brought us to creation of own local system of postgraduate
education using the next 4 basic principles: principle of robust internal base as
a platform for the following specialization, principle of repeating to fix the
knowledge, principle of knowledge control and last but not least principle of
active participation in educational system.
PMID- 25130635
TI - [Specifics of diabetes mellitus in women].
AB - Approximately 4 % of female population suffers from diabetes. A permanent
interaction between diabetes, its treatment and sex hormonal changes (childhood,
puberty, reproduction, pregnancy, menopause) occurs in those women. This review
article summarizes up to date published studies concerning reciprocal
relationship between diabetes and sexual development in women.
PMID- 25130638
TI - [Zdenek Maratka and his share in the founding of the Czech Gastroenterological
Society and its journal. Gastroenterological Society in Czech and Slovac
republics].
AB - Zdenek Maratka (1914-2010) was a leading person in a Czech and Slovak
gastroenterology in spite of the infavourable approach of the official communist
policy to him.. He was one of the founders of gastroenterology in Czechoslovakia.
He had been habilitated in 1948 for thesis Ulcerative colitis. Maratka stood at
the first steps of foundation of Czech Gastroenterology Society very soon after
the WW2 and followed with the preparation as a secretary ge-neral of the 8th
ASNEMGE Congress in Prague 1968 and as a president the 1st Congress of Endoscopy
in the very optimistic atmosphere of ,,Prague Spring". He was nominated or
elected by several international gastroenterology organisations, during 1976-1980
had been President of ESGE. He started with editoring of Czech gastroenterology
Association journal as a member of editorial board and had been its main editor
between 1969-1999. His well appreciated novelty in the magazine was a short
remarks in one or two sentences from the world scientific literature which
appeared in every copy. As an editor emeritus he supported the quality of the
journal by many advices and contributions including articles.
PMID- 25130639
TI - [Crohn's disease surgery].
AB - Surgery of Crohns disease is an important part of the general treatment
algorithm. The role of surgery is changing with the development of conservative
procedures. The recent years have seen the return to early treatment of patients
with Crohns disease. Given the character of the disease and its intestinal
symptoms, a specific approach to these patients is necessary, especially
regarding the correct choice of surgery. The paper focuses on the luminal damage
of the small and large intestine including complications of the disease. We
describe the individual indications for a surgical solution, including the choice
of anastomosis or multiple / repeated surgeries.
PMID- 25130640
TI - [Advances in diagnosis and therapy of inflammatory bowel diseases].
AB - The inflammatory bowel diseases have been an interesting topic not only for
gastroenterologists, but also for other medical professionals, since the
beginning of the last century, when this group of inflammatory autoimmune
diseases was revealed. Logically, the doyen of Czech gastroenterology, Professor
MUDr. Zdenek Maratka, DrSc., who dedicated a substantial part of his life to
research into inflammatory bowel disease, particularly ulcerative colitis, was no
exception. The current century is characterized by a very rapid development of
scientific research and almost immediate introduction of scientific knowledge
into clinical practice. In the area of inflammatory bowel diseases, the biggest
advances have been made in diagnosis and therapy. The examination of the small
bowel and large bowel by magnetic resonance belongs at the very pinnacle in the
non-invasive diagnosis of the lower part of the gastrointestinal tract. The
administration of biological therapy to patients with the most severe forms of
inflammatory bowel diseases should be considered a breakthrough since the
introduction of corticosteroids into the therapy of inflammatory bowel diseases
in the 1950s.
PMID- 25130641
TI - [Biological therapy in women with inflammatory bowel disease during pregnancy].
AB - The aim of this article is to objective review available research data regarding
the safety of biological therapies during pregnancy and breastfeeding in women
with inflammatory bowel disease. Biological therapies appear to be safe in
pregnancy, as no increased risk of malformations has been demonstrated. Available
clinical results suggest that the efficacy of infliximab and adalimumab in
achieving clinical response and maintaining remission in pregnant patients might
outweigh the theoretical risks of drug exposure to the fetus. If possible, anti
TNF therapy should be stopped by the end of the second trimester due to
transplacental transfer and potential risk for the fetus. The use of infliximab
and adalimumab is probably compatible with breastfeeding.
PMID- 25130642
TI - [Crohn's disease - etiopathogenetic factors].
AB - Crohn's disease is often purely inflammatory, but most patients develop
complicated disease with strictures or fistulae. Specific etiopathogenesis of
this severe disease is not definitely clear despite research efforts and learning
of many pathogenetic mechanisms. Many studies have suggested that NOD2 mutations
are associated with increased risk of complicated disease. Presence of NOD2
mutation itself is just one of factors contributing to development of this
disease. Genetically predisposed individuals in combination with influence of
environmental factors result in a disturbed innate (i.e., disturbed intestinal
barrier, Paneth cell dysfunction) and adaptive (i.e., imbalance of effector and
regulatory T cells and cytokines, migration and retention of leukocytes) immune
response towards a diminished diversity of commensal microbiota. Data of meta
analysis made so far provide ambiguous evidence to support top-down therapy based
solely on single NOD2 mutations, but suggest that targeted early-intensive
therapy for high-risk patients with two NOD2 mutations might be beneficial, but
more prospective trials could answer these questions.
PMID- 25130643
TI - [Etiology and pathogenesis of inflammatory bowel diseases].
AB - Zdenek Maratka has been the first physician, who had brought a new information
for the Czech medical community with topic of inflammatory bowel diseases, which
had been systematic studied for him. He had prepared an original theory - two
component hypothesis about origin of ulcerative colitis, which had been developed
and innovated by him for long time. From the international point of view, Maratka
has had an extraordinary impact and significant contribution for recognition of
ulcerative colitis and Crohn's disease. Despite the fact that the true origin of
ulcerative colitis and Crohn's disease (UC) still remain elusive, basic as well
as clinical research bring many new data on etiology and pathogenesis of this
inflammatory condition. It seems clear that IBD originate from interaction of
several intrinsic and extrinsic factors that contribute individually in a
particular patient. Among internal factors the genes play an important role,
because its influence on the mucosal immunity system and immunological response.
Among the external factors importance are recognized the gut microbiota content,
cigarette smoking and psychological stress.
PMID- 25130644
TI - [History of surgical treatment of non-specific inflammatory bowel diseases].
AB - Treatment of non-specific inflammatory bowel diseases was from the start
accompanied by forced operations. In the 19th and early 20th century operations
were burdened with high mortality, but most were more successful than the limited
possibilities of conservative treatment. Gradually developed principles for the
treatment of Crohns disease, a length of bowel sparing surgery are still valid
today. Surgical treatment of ulcerative colitis passed the time of colonic
irrigation, bypass surgery, limited resection to todays gold standard -
proctocolectomy with ileo-pouch-anal anastomosis.
PMID- 25130645
TI - [Epidemiology of dyspepsia].
AB - Epidemiology of uninvestigated dyspepsia was studied in the Czech Republic for
the first time in 2001. The aim of our current multi-centre prospective study was
to evaluate dyspepsia using the same methods in a representative sample of
general unselected population from the same geographical areas 10 years later. A
total of 22 centres entered the study. A total of 1,836 subjects (aged 5-98
years) were enrolled. The overall prevalence of dyspepsia was 12 %; namely 3.5 %
in subjects aged 5-24 years, 18 % among 25-64-year-old persons and 15 % in
subjects 65 years. Despite the substantial decrease of Helicobacter pylori
infection in the Czech Republic over the past 10 years, the prevalence and basic
socio-demographic determinants of uninvestigated dyspepsia did not change
significantly.
PMID- 25130646
TI - [Management of patients with dyspepsia].
AB - Dyspepsia is a common clinical problem with an extensive differential diagnosis
and a heterogeneous pathophysiology. Dyspepsia affects up to 40 % of the general
population and significantly reduces quality of life. According to the Rome III
criteria, dyspepsia is defined as one or more of the following symptoms:
epigastric pain and/or burning (classified as epigastric pain syndrome),
postprandial fullness and/or early satiation (classified as postprandial distress
syndrome). Initial evaluation should focus on the identification and treatment of
potential causes of symptoms such as gastroesophageal reflux disease, peptic
ulcer disease, and medication side effects but also on recognizing those at risk
for more serious conditions such as gastric cancer. An empiric PPI trial or "test
and treat" strategy for Helicobacter pylori are the initial approaches to a
patient with dyspepsia, followed by endoscopy if initial management fails. Once
an organic cause for symptoms is excluded, a diagnosis of functional dyspepsia is
made. This article will review the definition, etiology, and general approach to
the evaluation and management of the patient with dyspepsia including the role of
proton-pump inhibitors, treatment of Helicobacter pylori, and endoscopy.
PMID- 25130647
TI - [Endoscopic classification of colon and rectal neoplasias].
AB - Along with the dynamic evolution of the new field of digestive endoscopy, the
need of unified and unambiguous terms for endoscopic findings arose in the second
half of the 20th century. In collaboration with the OMED members, professor
Zdenek Maratka drew up the first internationally acknowledged terminology for
digestive endoscopy which was used in the full range for a period of almost 20
years. The technical progress later brought with it endoscopes which made it
possible to view flat lesions, frequently overlooked until then. The
classification of the surface lesions was further specified by the Paris
Classification which drew from the experience of Japanese endoscopists. Thanks to
the new endoscopic methods of imaging mucosa in vivo and the pit-pattern and
vascular-pattern classification, we can currently estimate the biological nature
of lesion with great accuracy and therefore choose the best therapeutic
procedure.
PMID- 25130649
TI - Efficacy of low-dose human chorionic gonadotropin therapy in dogs with
spermatogenic dysfunction: a preliminary study.
AB - Human chorionic gonadotropin (hCG) is a glycoprotein used in the treatment of
spermatogenic dysfunction. However, previous studies performed in dogs show that
repeated administration of large doses of hCG produces antibodies against hCG. In
this study, we examined the efficacy of low-dose injections of hCG in four male
dogs with spermatogenic dysfunction and low plasma testosterone (T) levels. We
administered 100 IU hCG per animal, five times at 3-day intervals, and evaluated
the changes in semen quality and plasma T levels. The total number of sperm in
ejaculate, the percentage of progressively motile sperm and the plasma T levels
had increased by 3-5 weeks after the first injection of hCG in three of the four
dogs, but were unchanged in the fourth dog. These findings indicate that
temporary improvement of the semen quality of dogs with spermatogenic dysfunction
and low plasma T levels is possible after five low-dose injections of hCG.
PMID- 25130648
TI - Engineering persister-specific antibiotics with synergistic antimicrobial
functions.
AB - Most antibiotics target growth processes and are ineffective against persister
bacterial cells, which tolerate antibiotics due to their reduced metabolic
activity. These persisters act as a genetic reservoir for resistant mutants and
constitute a root cause of antibiotic resistance, a worldwide problem in human
health. We re-engineer antibiotics specifically for persisters using tobramycin,
an aminoglycoside antibiotic that targets bacterial ribosomes but is ineffective
against persisters with low metabolic and cellular transport activity. By giving
tobramycin the ability to induce nanoscopic negative Gaussian membrane curvature
via addition of 12 amino acids, we transform tobramycin itself into a transporter
sequence. The resulting molecule spontaneously permeates membranes, retains the
high antibiotic activity of aminoglycosides, kills E. coli and S. aureus
persisters 4-6 logs better than tobramycin, but remains noncytotoxic to
eukaryotes. These results suggest a promising paradigm to renovate traditional
antibiotics.
PMID- 25130650
TI - Long-term therapeutic and reporter gene expression in lentiviral vector treated
cystic fibrosis mice.
AB - BACKGROUND: Persistent reporter gene and cystic fibrosis transmembrane
conductance regulator (CFTR) nasal airway gene expression can be achieved with a
single lentiviral (LV) gene vector dosing when coupled with a preparatory
lysophosphatidylcholine (LPC) airway pre-treatment. In the present study, we
characterised the duration of gene expression in individual cystic fibrosis (CF)
knockout mice (cftr(tm1unc)) over their lifetimes. METHODS: CF mouse nasal
airways were treated with LV-Rx, a mixture of a therapeutic LV-CFTR gene vector
and a LV-luciferase reporter gene vector, after pre-treatment with LPC. Control
groups received either PBS sham pre-treatment followed by LV-Rx, or LPC prior to
delivery of a LV vector containing no transgene (LV-MT). Airway reporter gene
expression was monitored by bioluminescence, and functional CFTR expression was
assessed via nasal transepithelial potential difference measurements at regular
intervals up to 21 months. The presence of the CFTR transgene in the nasal septa,
liver and spleen tissues were assessed by a quantitative polymerase chain
reaction. Circulating antibodies to the vector glycoprotein envelope and to the
luciferase protein were also measured. RESULTS: The combined use of LPC and LV
gene vectors in the nasal airway produced enhanced and sustained luciferase and
CFTR gene expression lasting at least 12 months. Improved survival was also
observed in CF knockout mice treated with the LV vector mixture compared to all
control CF mouse groups. CONCLUSIONS: The present study showed that our airway
pre-treatment and gene delivery technique resulted in sustained functional CFTR
expression and improved survival in CF mice.
PMID- 25130651
TI - Association between combative behavior requiring intervention and delirium in
hospitalized patients.
AB - BACKGROUND: We hypothesized that delirium contributes to combative behavior
requiring intervention in hospitalized patients. Delirium identification would
therefore potentially provide an opportunity for prevention and early
identification of patients at risk, thereby improving safety for patients and
staff. OBJECTIVE: To determine whether delirium is associated with combative
behavior requiring intervention in a general hospital population. DESIGN: Case
control study. SETTING: A 336-bed, nonuniversity, teaching hospital serving
adults in the Pacific Northwest. PATIENTS: One hundred twenty consecutive
hospitalized patients with combative behavior requiring intervention compared to
159 randomly selected inpatient control subjects, all from 2011. INTERVENTION:
Bivariate statistics were used to compare demographics; diagnoses; presence of
delirium, dementia, substance use, other psychiatric diagnosis; medications;
hospital length of stay; and discharge disposition. We used stepwise logistic
regression to determine the association of combative behavior requiring
intervention with delirium after adjustment for covariates. RESULTS: Delirium
preceding the combative behavior was present in 50% (60/120) of patients with
combative behavior requiring intervention compared to 16% (26/159) of controls (P
< 0.001). Combative-behavior patients were hospitalized longer (9.4 vs 4.5 days,
P < 0.001), and were more likely to be discharged to a skilled nursing facility
(26%, 31/120) or to leave against medical advice (10%, 12/120, P < 0.001).
Delirium was strongly associated with combative behavior requiring intervention,
after adjustment (odds ratio: 3.8, 95% confidence interval: 2.0-7.3, P < 0.001).
CONCLUSION: Delirium is strongly associated with combative behavior requiring
intervention, which poses a significant safety risk for patients and staff.
PMID- 25130652
TI - Klotho suppresses renal tubulo-interstitial fibrosis by controlling basic
fibroblast growth factor-2 signalling.
AB - Increased basic fibroblast growth factor-2 (FGF2) and reduced Klotho have both
been reported to be closely associated with renal fibrosis. However, the
relationship between Klotho and FGF2 remains unclear. We demonstrate that FGF2
induced tubulo-epithelial plasticity in cultured HK-2 cells, accompanied by a
reduction in Klotho expression, whereas recombinant Klotho protein could inhibit
the action of FGF2. The FGF2 effects required extracellular signal-regulated
protein kinase 1/2 activation, which was suppressed by Klotho. Moreover, Klotho
also restrained FGF2-induced fibroblast proliferation and activation. The
inhibitory effect of Klotho on the activity of FGF2 was likely due to its potent
ability to compete with FGF2 binding to FGF receptor 1. Unilateral ureteral
obstruction (UUO)-induced renal fibrosis was associated with an increase in FGF2
and a reduction in Klotho expression in wild-type mice, whereas FGF2(-/-) mice
largely preserved Klotho expression and developed only mild renal fibrosis after
obstructive injury. Furthermore, administration of Klotho protein in UUO mice
significantly reduced renal fibrosis, concomitant with a marked suppression of
FGF2 production and signalling. These studies demonstrate a feedback loop between
Klotho depletion and FGF2 activation in renal fibrosis. Our results also suggest
that Klotho treatment reduces renal fibrosis, at least in part, by inhibiting
FGF2 signalling.
PMID- 25130653
TI - Telocytes in liver regeneration: possible roles.
AB - Telocytes (TCs) are a novel type of interstitial cells which are potentially
involved in tissue regeneration and repair (www.telocytes.com). Previously, we
documented the presence of TCs in liver. However, the possible roles of TCs in
liver regeneration remain unknown. In this study, a murine model of partial
hepatectomy (PH) was used to induce liver regeneration. The number of TCs
detected by double labelling immunofluorescence methods (CD34/PDGFR-alpha,
CD34/PDGFR-beta and CD34/Vimentin) was significantly increased when a high level
of hepatic cell proliferation rate (almost doubled) as shown by 5-ethynyl-2'
deoxyuridine (EdU) immunostaining and Western Blot of Proliferating cell nuclear
antigen (PCNA) was found at 48 and 72 hrs post-PH. Meanwhile, the number of CK-19
positive-hepatic stem cells peaked at 72 hrs post-PH, co-ordinating with the same
time-point, when the number of TCs was most significantly increased. Taken
together, the results indicate a close relationship between TCs and the cells
essentially involved in liver regeneration: hepatocytes and stem cells. It
remains to be determined how TCs affect hepatocytes proliferation and/or hepatic
stem cell differentiation in liver regeneration. Besides intercellular junctions,
we may speculate a paracrine effect via ectovesicles.
PMID- 25130654
TI - Slit2 is decreased after spontaneous labour in myometrium and regulates pro
labour mediators.
AB - Preterm birth, a global healthcare problem, is commonly associated with
inflammation. As Slit2 plays an emerging role in inflammation, the purpose of
this study was to determine the effect of Slit2 on labour mediators in human
gestational tissues. Slit2 mRNA and protein expression were assessed using qRT
PCR and immunohistochemistry in foetal membranes and myometrium obtained before
and after labour. Slit2 silencing was achieved using siRNA in primary myometrial
cells. Pro-inflammatory and pro-labour mediators were evaluated by qRT-PCR, ELISA
and gelatin zymography. Slit2 mRNA and protein expression were found to be
significantly lower in myometrium after labour onset. There was no effect of term
or preterm labour on Slit2 expression in foetal membranes. Slit2 mRNA expression
was decreased in myometrium treated with LPS and IL-1beta. Slit2 siRNA in
myometrial cells increased IL-1beta-induced pro-inflammatory cytokine gene
expression and release (IL-6 and IL-8), COX-2 expression and prostaglandin PGE2
and PGF2alpha release, and MMP-9 gene expression and pro MMP-9 release. There was
no effect of Slit2 siRNA on IL-1beta-induced NF-kappaB transcriptional activity.
Our results demonstrate that Slit2 is decreased in human myometrium after labour
and our knock-down studies describe an anti-inflammatory effect of Slit2 in
myometrial cells.
PMID- 25130655
TI - Pollination ecology and inbreeding depression control individual flowering
phenologies and mixed mating.
AB - We analyze evolution of individual flowering phenologies by combining an
ecological model of pollinator behavior with a genetic model of inbreeding
depression for plant viability. The flowering phenology of a plant genotype
determines its expected daily floral display which, together with pollinator
behavior, governs the population rate of geitonogamous selfing (fertilization
among flowers on the same plant). Pollinators select plant phenologies in two
ways: they are more likely to visit plants displaying more flowers per day, and
they influence geitonogamous selfing and consequent inbreeding depression via
their abundance, foraging behavior, and pollen carry-over among flowers on a
plant. Our model predicts two types of equilibria at stable intermediate selfing
rates for a wide range of pollinator behaviors and pollen transfer parameters.
Edge equilibria occur at maximal or minimal selfing rates and are constrained by
pollinators. Internal equilibria occur between edge equilibria and are determined
by a trade-off between pollinator attraction to large floral displays and
avoidance of inbreeding depression due to selfing. We conclude that unavoidable
geitonogamous selfing generated by pollinator behavior can contribute to the
common occurrence of stable mixed mating in plants.
PMID- 25130656
TI - A presenilin 1 mutation in the first case of Alzheimer's disease: revisited.
AB - BACKGROUND: Recently, a single point mutation in the presenilin 1 (PSEN1) gene of
the first described Alzheimer's disease (AD) patient Auguste D was reported by
Muller and co-workers. However, the sequencing results of the DNA from a 100-year
old tissue contained some uncertainties. METHODS: We heat extracted DNA from an
original histological slice of Auguste D's brain and used nested polymerase chain
reaction for the amplification of different exons of genes known to be affected
in familial forms of AD. RESULTS: Our sequencing analysis did not validate the
reported mutation. Furthermore, an extended sequencing analysis of Auguste D's
DNA revealed no indication of a nonsynonymous hetero- or homozygous mutation in
the exons of APP, PSEN1, and PSEN2 genes comprising the already known familial AD
mutations. CONCLUSION: Despite the wealth of data from Muller and co-workers, our
results emphasize the requirement of more detailed analysis of Auguste D's DNA in
future.
PMID- 25130657
TI - Identification of preclinical Alzheimer's disease by a profile of pathogenic
proteins in neurally derived blood exosomes: A case-control study.
AB - BACKGROUND: Proteins pathogenic in Alzheimer's disease (AD) were extracted from
neurally derived blood exosomes and quantified to develop biomarkers for the
staging of sporadic AD. METHODS: Blood exosomes obtained at one time-point from
patients with AD (n = 57) or frontotemporal dementia (FTD) (n = 16), and at two
time-points from others (n = 24) when cognitively normal and 1 to 10 years later
when diagnosed with AD were enriched for neural sources by immunoabsorption. AD
pathogenic exosomal proteins were extracted and quantified by enzyme-linked
immunosorbent assays. RESULTS: Mean exosomal levels of total tau, P-T181-tau, P
S396-tau, and amyloid beta 1-42 (Abeta1-42) for AD and levels of P-T181-tau and
Abeta1-42 for FTD were significantly higher than for case-controls. Step-wise
discriminant modeling incorporated P-T181-tau, P-S396-tau, and Abeta1-42 in AD,
but only P-T181-tau in FTD. Classification of 96.4% of AD patients and 87.5% of
FTD patients was correct. In 24 AD patients, exosomal levels of P-S396-tau, P
T181-tau, and Abeta1-42 were significantly higher than for controls both 1 to 10
years before and when diagnosed with AD. CONCLUSIONS: Levels of P-S396-tau, P
T181-tau, and Abeta1-42 in extracts of neurally derived blood exosomes predict
the development of AD up to 10 years before clinical onset.
PMID- 25130659
TI - Survival and early recourse to care for dementia: A population based study.
AB - BACKGROUND: A large proportion of dementia cases are still undiagnosed. Although
early dementia care has been hypothesized to benefit both patients and families,
evidence-based benefits are lacking. Thus, investigating the benefits for newly
demented persons according to their recourse to care in the "real life" appears
critical. METHODS: We examined the relation between initial care recourse care
and demented individuals' survival in a large cohort of incident dementia cases
screened in a prospective population-based cohort, the Three-City Study. We
assessed recourse to care for cognitive complaint at the early beginning of
dementia when incident cases were screened. We classified patients in three
categories: no care recourse, general practitioner consultation or specialist
consultation. We used proportional hazard regression models to test the
association between recourse to care and mortality, adjusting on socio
demographical and clinical characteristics. RESULTS: Two hundred and fifty-three
incident dementia participants were screened at the 2 year or 4 year follow-up.
One third of the incident demented individuals had not consulted a physician for
cognitive problems. Eighty-six (34.0%) individuals had reported a cognitive
problem only to their general practitioner (GP) and 80 (31.6%) had consulted a
specialist. Mean duration of follow-up after incident dementia was 5.1 years,
during which 146 participants died. After adjustment on potential confounders,
participants who had consulted a specialist early in the disease course presented
a poorer survival than those who did not consult any physician (hazard ratio =
1.64, 95% confidence interval 1.03-2.62). There was a trend but no significant
differential survival profile between participants who complained to their GP and
those without any care recourse. CONCLUSION: Neither recourse to a specialist nor
recourse to GP improve survival of new dementia cases. Those who had consulted a
specialist early in the disease course even reported a worse life expectancy than
those who did not.
PMID- 25130658
TI - Delphi definition of the EADC-ADNI Harmonized Protocol for hippocampal
segmentation on magnetic resonance.
AB - BACKGROUND: This study aimed to have international experts converge on a
harmonized definition of whole hippocampus boundaries and segmentation
procedures, to define standard operating procedures for magnetic resonance (MR)
based manual hippocampal segmentation. METHODS: The panel received a
questionnaire regarding whole hippocampus boundaries and segmentation procedures.
Quantitative information was supplied to allow evidence-based answers. A
recursive and anonymous Delphi procedure was used to achieve convergence.
Significance of agreement among panelists was assessed by exact probability on
Fisher's and binomial tests. RESULTS: Agreement was significant on the inclusion
of alveus/fimbria (P = .021), whole hippocampal tail (P = .013), medial border of
the body according to visible morphology (P = .0006), and on this combined set of
features (P = .001). This definition captures 100% of hippocampal tissue, 100% of
Alzheimer's disease-related atrophy, and demonstrated good reliability on
preliminary intrarater (0.98) and inter-rater (0.94) estimates. DISCUSSION:
Consensus was achieved among international experts with respect to hippocampal
segmentation using MR resulting in a harmonized segmentation protocol.
PMID- 25130660
TI - Diagnostic value of dilated intercellular space and histopathologic scores in
gastroesophageal reflux disease.
AB - The aim of this paper is to investigate the diagnostic value of histopathologic
score and the dilated intercellular space (DIS) in patients with gastroesophageal
reflux disease (GERD) and functional heartburn (FH). Participants with GERD
symptoms including reflux esophagitis, non-erosive reflux disease (NERD),
Barrett's esophagus (BE), functional heartburn (FH), along with a control group
with atypical GERD-like symptom (Sym-C), and asymptomatic healthy volunteers (H
C) were administered GERD questionnaire, and subjected to endoscopy and biopsies,
as well as 24-hour pH-impedance monitoring. Biopsies were evaluated using
standards from the 2011 Esohisto Project after Hematoxylin-Eosin staining. DIS
was measured quantitatively under light microscopy. Among the total of 565
participants with qualified biopsy specimens, the mean DIS of the reflux
esophagitis (RE) group was significantly wider compared with the other five
groups. DIS in patients with GERD-like symptoms was significantly wider compared
with the H-C. No significant differences were observed between NERD and FH.
Results from 24-hour pH-impedance monitoring indicated that only the DIS of
patients with acid reflux or the amount of acid reflux episodes in patients with
DIS was significantly wider compared with patients with nonacid reflux or
patients without DIS (P < 0.001). With DIS = 0.9 MUm as the cutoff value, the
sensitivity and specificity were 62.6% and 54.1%, respectively. Using the total
histopathologic score > 3 as the diagnostic criterion, the sensitivity and
specificity were 71.7% and 47.4%. DIS is closely associated with GERD and acid
reflux. The diagnostic value of histological scores in lower esophagus in GERD is
very similar to that of the quantitative measurement of DIS.
PMID- 25130662
TI - SUN11602 has basic fibroblast growth factor-like activity and attenuates neuronal
damage and cognitive deficits in a rat model of Alzheimer's disease induced by
amyloid beta and excitatory amino acids.
AB - Basic fibroblast growth factor (bFGF/FGF-2) is known to possess neuroprotective
and neurite outgrowth activity properties. In this study, the effects of a novel
synthetic compound that mimics the neuroprotective properties of bFGF - SUN11602
were examined in vitro and in vivo. SUN11602 promoted neurite outgrowth of
primarily cultured rat hippocampal neurons. For the in vivo study, an Alzheimer's
disease (AD) model with severe damage to the hippocampal tissue was constructed
by injecting the hippocampi of rats with aggregated Abeta1-40, followed 48 h
later by an injection of ibotenate [an agonist for N-methyl-d-aspartate (NMDA)
receptor]. Oral administration of SUN11602 at the midpoint of Abeta1-40 and
ibotenate injections attenuated short-term memory impairment in the Y-maze test,
as well as spatial learning deficits in the water maze task. In addition, the
SUN11602 treatment inhibited the increase of peripheral-type benzodiazepine
binding sites (PTBBS), which are a marker for gliosis. A negative correlation was
found between PTBBS numbers and learning capacity in the water maze task. These
results suggest that SUN111602 improved memory and learning deficits in the
hippocampally lesioned rats by preventing neuronal death and/or promotion of
neurite outgrowth. Taken together, these results indicate that SUN11602, a bFGF
like compound with neuroprotective and neurite outgrowth activity, may be
beneficial for the treatment of progressive neurodegenerative diseases such as
AD.
PMID- 25130663
TI - A new Drosophila model to study the interaction between genetic and environmental
factors in Parkinson's disease.
AB - The fruit fly Drosophila melanogaster has long been used as a model organism for
human diseases, including Parkinson's disease (PD). Its short lifespan, simple
maintenance, and the widespread availability of genetic tools allow researchers
to study disease mechanisms as well as potential drug therapies. Many different
PD models have already been developed, including ones utilizing mutated alpha-Syn
and chronic exposure to rotenone. However, few animal models have been used to
study interaction between the PD causing factors. In this study, we developed a
new model of PD for use in the larval stage in order to study interaction between
genetic and environmental factors. First, the 3rd instar larvae (90-94 hours
after egg laying) expressing a mutated form of human alpha-Syn (A53T) in
dopaminergic (DA) neurons were video-taped and quantified for locomotion (e.g.
crawling pattern and speed) using ImageJ software. A53T mutant larvae showed
locomotion deficits and also loss of DA neurons in age-dependent manner.
Similarly, larvae chronically exposed to rotenone (10 MUM in food) showed age
dependent decline in locomotion accompanied by loss of DA neurons. We further
show that combining the two models, by exposing A53T mutant larvae to rotenone,
causes a much more severe PD phenotype (i.e. locomotor deficit). Our finding
shows interaction between genetic and environmental factors underlying
development of PD symptoms. This model can be used to further study mechanisms
underlying the interaction between genes and different environmental PD factors,
as well as to explore potential therapies for PD treatment.
PMID- 25130665
TI - Internal and external spatial attention examined with lateralized EEG power
spectra.
AB - Several authors argued that retrieval of an item from visual short term memory
(internal spatial attention) and focusing attention on an externally presented
item (external spatial attention) are similar. Part of the neuroimaging support
for this view may be due to the employed experimental procedures. Furthermore, as
internal spatial attention may have a more induced than evoked nature some
effects may not have been visible in event related analyses of the
electroencephalogram (EEG), which limits the possibility to demonstrate
differences. In the current study, a colored frame cued which stimulus, one out
of four presented in separate quadrants, required a response, which depended on
the form of the cued stimulus (circle or square). Importantly, the frame occurred
either before (precue), simultaneously with (simultaneous cue), or after the
stimuli (postcue). The precue and simultaneous cue condition both concern
external attention, while the postcue condition implies the involvement of
internal spatial attention. Event-related lateralizations (ERLs), reflecting
evoked effects, and lateralized power spectra (LPS), reflecting both evoked and
induced effects, were determined. ERLs revealed a posterior contralateral
negativity (PCN) only in the precue condition. LPS analyses on the raw EEG showed
early increased contralateral theta power at posterior sites and later increased
ipsilateral alpha power at occipito-temporal sites in all cue conditions.
Responses were faster when the internally or externally attended location
corresponded with the required response side than when not. These findings
provide further support for the view that internal and external spatial attention
share their underlying mechanism.
PMID- 25130661
TI - The protective role of prosaposin and its receptors in the nervous system.
AB - Prosaposin (also known as SGP-1) is an intriguing multifunctional protein that
plays roles both intracellularly, as a regulator of lysosomal enzyme function,
and extracellularly, as a secreted factor with neuroprotective and glioprotective
effects. Following secretion, prosaposin can undergo endocytosis via an
interaction with the low-density lipoprotein-related receptor 1 (LRP1). The
ability of secreted prosaposin to promote protective effects in the nervous
system is known to involve activation of G proteins, and the orphan G protein
coupled receptors GPR37 and GPR37L1 have recently been shown to mediate signaling
induced by both prosaposin and a fragment of prosaposin known as prosaptide. In
this review, we describe recent advances in our understanding of prosaposin, its
receptors and their importance in the nervous system.
PMID- 25130666
TI - Role of Re species and acid cocatalyst on Ir-ReOx /SiO2 in the C-O hydrogenolysis
of biomass-derived substrates.
AB - The catalytic performance of ReOx -modified Ir metal catalyst in the
hydrogenolysis of C-O bonds is strongly dependent on the choice of solvent. The
acidic property of the Re species becomes obvious in the alkane solvent, and the
hydrogenolysis reaction proceeds mainly by acid-catalyzed dehydration and the
subsequent metal-catalyzed hydrogenation. The acidic property of the Re species
is weakened in water; however, the hydrogenolysis reaction proceeds in water via
a direct mechanism involving SN 2-like attack of a hydride species at the
interface between Ir and ReOx on the adsorbed Re alkoxide species. This mechanism
enabled the selective dissociation of the C-O bond neighboring the CH2 OH group.
PMID- 25130664
TI - Kisspeptin-10 potentiates miniature excitatory postsynaptic currents in the rat
supraoptic nucleus.
AB - Kisspeptin is the natural ligand of the G protein-coupled receptor -54 and plays
a major role in gonadotropin-releasing hormone secretion in the hypothalamus.
Kisspeptin-10 is an endogenous derivative of kisspeptin and has 10 -amino acids.
Previous studies have demonstrated that central administration of kisspeptin-10
stimulates the secretion of arginine vasopressin (AVP) in male rats. We examined
the effects of kisspeptin-10 on- excitatory synaptic inputs to magnocellular
neurosecretory cells (MNCs) including AVP neurons in the supraoptic nucleus (SON)
by obtaining in vitro whole-cell patch-clamp recordings from slice preparations
of the rat brain. The application of kisspeptin-10 (100 nM-1 MUM) significantly
increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) in
a dose-related manner without affecting the amplitude. The kisspeptin-10-induced
potentiation of the mEPSCs was significantly attenuated by previous exposure to
the kisspeptin receptor antagonist kisspeptin-234 (100 nM) and to the protein
kinase C inhibitor bisindolylmaleimide I (20 nM). These results suggest that
kisspeptin-10 participates in the regulation of synaptic inputs to the MNCs in
the SON by interacting with the kisspeptin receptor.
PMID- 25130668
TI - Association between right ventricular dysfunction and restrictive lung disease in
childhood cancer survivors as measured by quantitative echocardiography.
AB - BACKGROUND: Restrictive lung disease is a complication in childhood cancer
survivors who received lung-toxic chemotherapy and/or thoracic radiation. Left
ventricular dysfunction is documented in these survivors, but less is known about
right ventricular (RV) function. Quantitative echocardiography may help detect
subclinical RV dysfunction. The aim of this study was to assess RV function
quantitatively in childhood cancer survivors after lung-toxic therapy.
PROCEDURES: We identified records of 33 childhood cancer survivors who (1) were
treated with lung-toxic therapy and/or radiation, (2) were cancer-free for >= one
year after therapy, and (3) had pulmonary function tests and echocardiograms from
their most recent follow-up visit. RESULTS: Participants' mean age was 11.6 +/-
4.5 years at cancer diagnosis and 23 +/- 8.6 years at evaluation. The most common
diagnosis was lymphoma/leukemia (n = 27). Twenty-nine subjects had anthracycline
exposure. Eleven of the 33 subjects demonstrated restrictive pulmonary impairment
(total lung capacity 3.69 +/- 1.5 L [69.3 +/- 22.4% predicted]). Among
quantitative measures of RV function, isovolumetric acceleration (IVA), a measure
of contractility, was significantly lower in the group with restrictive lung
disease (2.42 +/- 0.56 vs. 1.83 +/- 0.78 m/sec(2); P < 0.05). There was a trend
towards lower tissue Doppler derived S' and tricuspid annular plane systolic
excursion in the group with restrictive lung disease. Subjects with restrictive
lung disease were found to have >= 2 abnormal parameters (P < 0.01). CONCLUSION:
IVA may detect early RV dysfunction in childhood cancer survivors with
restrictive lung disease. Our findings require confirmation in a larger study
population and validation by cardiac MRI.
PMID- 25130667
TI - D-Cycloserine ameliorates social alterations that result from prenatal exposure
to valproic acid.
AB - Prenatal exposure to valproic acid (VPA) alters rodent social interactions in a
dose-dependent way: exposure to a high dose of VPA (>500 mg/kg) mid-gestation
decreases social interactions whereas a moderate dose of VPA (350 mg/kg)
increases peer-directed social behavior. The moderate dose also decreases
expression of the mRNA for serine in amygdala and orbitofrontal cortex. In this
study, we examined whether d-cycloserine could ameliorate VPA-induced alterations
in ultrasonic vocalizations (USVs), social interactions, and locomotor activity.
Pregnant Sprague Dawley rats were given intraperintoneal injections of VPA
(200mg/kg each) on gestational days 12, 12.5 and 13; controls were injected with
saline. Offspring received a subcutaneous injection of saline or d-cycloserine
(32 or 64 mg/kg) either acutely (1h prior to testing) or repeatedly (once per day
for four days). Social interactions were assessed during late adolescence, and
USVs were recorded concomitantly. Male and female rats that were exposed to VPA
demonstrated more locomotor activity than control animals during habituation to
the testing chamber. VPA-exposed males showed increased play fighting. d
Cycloserine normalized the VPA-induced increase in play fighting in males and
also increased social motivation in females. When the pair contained a VPA
exposed rat, significantly fewer USVs were emitted and 16% of the vocalizations
were of a novel waveform. These effects were not seen in pairs containing VPA
exposed animals that were treated with d-cycloserine. Overall, these findings are
consistent with data from other laboratories suggesting that d-cycloserine may be
a promising pharmacotherapeutic compound for improving social behavior disorders.
PMID- 25130669
TI - Mechano-actuated ultrafast full-colour switching in layered photonic hydrogels.
AB - Photonic crystals with tunability in the visible region are of great interest for
controlling light diffraction. Mechanochromic photonic materials are periodically
structured soft materials designed with a photonic stop-band that can be tuned by
mechanical forces to reflect specific colours. Soft photonic materials with broad
colour tunability and fast colour switching are invaluable for application. Here
we report a novel mechano-actuated, soft photonic hydrogel that has an ultrafast
response time, full-colour tunable range, high spatial resolution and can be
actuated by a very small compressive stress. In addition, the material has
excellent mechanical stability and the colour can be reversibly switched at high
frequency more than 10,000 times without degradation. This material can be used
in optical devices, such as full-colour display and sensors to visualize the time
evolution of complicated stress/strain fields, for example, generated during the
motion of biological cells.
PMID- 25130670
TI - Molecular crystals by design?
AB - In this Viewpoint, the impact of the paper published by Gautam R. Desiraju and
Angelo Gavezzotti (J. Chem. Soc., Chem. Commun., 1989, 621) upon the development
of Crystal Engineering, now recognised a key discipline in contemporary
chemical/pharmaceutical/materials science, is discussed.
PMID- 25130671
TI - Epidermal axonal swellings in painful and painless diabetic peripheral
neuropathy.
AB - INTRODUCTION: The pathophysiology of neuropathic pain (NeP) in diabetic
peripheral neuropathy (DPN) is unclear. A potential pathological feature
associated with intraepidermal nerve fiber density (IENFD) loss in DPN is axonal
swellings. METHODS: We determined the prevalence of intraepidermal axonal
swellings in DPN patients with or without NeP and compared the findings with
diabetes patients without DPN, patients with idiopathic neuropathy with NeP, and
control subjects. The primary outcome measure was the ratio of axonal swellings
to IENFD. Secondary outcome measures included clinical neuropathy severity and
assessment for messenger RNA for voltage-gated sodium and calcium channels.
RESULTS: IENFD was depressed in DPN (with/without pain) and in idiopathic
neuropathy patients. Axonal swelling ratios were similar for DPN subjects with
and without pain. There was no overexpression of voltage-gated ion channels in
epidermis from DPN patients. Clinical neuropathy severity was only related to
IENFD. CONCLUSIONS: There was no clinical relationship to pain or clinical
neuropathy severity for axonal swellings in DPN.
PMID- 25130672
TI - A simplified method to estimate body growth parameters of the European eel
Anguilla anguilla.
AB - A simple approach is proposed to fit a body growth model for the European eel
Anguilla anguilla to data-poor case studies. The model is a modified von
Bertalanffy curve allowing for delayed sex determination and sexual dimorphism.
The proposed procedure provides preliminary estimates of model parameters on the
basis of average age and body length of silver eels.
PMID- 25130673
TI - Liver allocation: can we ever get it right and should we ever get it right?
PMID- 25130675
TI - Implementation of an emergency department sign-out checklist improves transfer of
information at shift change.
AB - BACKGROUND: Transitions of care are ubiquitous in the emergency department (ED)
and inevitably introduce the opportunity for errors. Few emergency medicine
residency programs provide formal training or a standard process for patient
handoffs. Checklists have been shown to be effective quality-improvement measures
in inpatient settings and may be a feasible method to improve ED handoffs.
OBJECTIVE: To determine if the use of a sign-out checklist improves the accuracy
and efficiency of resident sign-out in the ED. METHODS: A prospective pre
/postinterventional study of residents rotating in the ED at a tertiary academic
medical center. Trained research assistants observed resident sign-out during
shift change over a 2-week period and completed a data collection tool to
indicate whether or not key components of sign-out occurred and time to sign out
each patient. An electronic sign-out checklist was implemented using a multi
faceted educational effort. A 2-week postintervention observation phase was
conducted. Proportions, means, and nonparametric comparison tests were calculated
using STATA. RESULTS: One hundred fifteen sign-outs were observed prior to
checklist implementation and 114 were observed after. Significant improvements
were seen in four sign-out components: reporting of history of present illness
increased from 81% to 99%, ED course increased from 75% to 86%, likely diagnosis
increased from 60% to 77%, and team awareness of plan increased from 21% to 41%.
Use of the repeat-back technique decreased from 13% to 5% after checklist
implementation and time to sign-out showed no significant change. CONCLUSION:
Implementation of a checklist improved the transfer of information without
increasing time to sign-out.
PMID- 25130674
TI - Degradation of toluene by ortho cleavage enzymes in Burkholderia fungorum FLU100.
AB - Burkholderia fungorum FLU100 simultaneously oxidized any mixture of toluene,
benzene and mono-halogen benzenes to (3-substituted) catechols with a selectivity
of nearly 100%. Further metabolism occurred via enzymes of ortho cleavage
pathways with complete mineralization. During the transformation of 3
methylcatechol, 4-carboxymethyl-2-methylbut-2-en-4-olide (2-methyl-2-enelactone,
2-ML) accumulated transiently, being further mineralized only after a lag phase
of 2 h in case of cells pre-grown on benzene or mono-halogen benzenes. No lag
phase, however, occurred after growth on toluene. Cultures inhibited by
chloramphenicol after growth on benzene or mono-halogen benzenes were unable to
metabolize 2-ML supplied externally, even after prolonged incubation. A control
culture grown with toluene did not show any lag phase and used 2-ML as a
substrate. This means that 2-ML is an intermediate of toluene degradation and
converted by specific enzymes. The conversion of 4-methylcatechol as a very minor
by-product of toluene degradation in strain FLU100 resulted in the accumulation
of 4-carboxymethyl-4-methylbut-2-en-4-olide (4-methyl-2-enelactone, 4-ML) as a
dead-end product, excluding its nature as a possible intermediate. Thus, 3
methylcyclohexa-3,5-diene-1,2-diol, 3-methylcatechol, 2-methyl muconate and 2-ML
were identified as central intermediates of productive ortho cleavage pathways
for toluene metabolism in B. fungorum FLU100.
PMID- 25130676
TI - Genetic variability in anthocyanin composition and nutritional properties of
blue, purple, and red bread (Triticum aestivum L.) and durum (Triticum turgidum
L. ssp. turgidum convar. durum) wheats.
AB - Renewed interest in breeding for high anthocyanins in wheat (Triticum ssp.) is
due to their antioxidant potential. A collection of different pigmented wheats
was used to investigate the stability of anthocyanins over three crop years. The
data show higher anthocyanins in blue-aleurone bread wheat (Triticum aestivum
L.), followed by purple- and red-pericarp durum wheat (Triticum turgidum L. ssp.
turgidum convar. durum), using cyanidin 3-O-glucoside as standard. HPLC of the
anthocyanin components shows five to eight major anthocyanins for blue wheat
extracts, compared to three anthocyanins for purple and red wheats. Delphinidin 3
O-rutinoside, delphinidin 3-O-glucoside, and malvidin 3-O-glucoside are
predominant in blue wheat, with cyanidin 3-O-glucoside, peonidin 3-O-galactoside,
and malvidin 3-O-glucoside in purple wheat. Of the total anthocyanins, 40-70%
remain to be structurally identified. The findings confirm the high heritability
for anthocyanins, with small genotype * year effects, which will be useful for
breeding purposes, to improve the antioxidant potential of cereal-based foods.
PMID- 25130677
TI - Comparison of adenocarcinoma (ACA) and squamous cell carcinoma (SCC) of the
uterine cervix in a sub-optimally screened cohort: a population-based
epidemiologic study of 51,842 women in Brazil.
AB - BACKGROUND: Most cancers of the uterine cervix are SCC, but the relative and
absolute incidence of ACA has risen in recent years, and ACA now accounts for
approximately 20% of invasive cervical cancers in the screened populations
worldwide. OBJECTIVE: To compare the epidemiological, clinical characteristics,
and treatment outcomes of ACA with those of SCC of the cervix in a sub-optimally
screened population. METHODS: Data from cervical cancer patients with SCC and ACA
treated from 2000 through 2009 were obtained from the Brazilian Hospital Cancer
Register databases. The summary odds ratios and chi-square tests were estimated.
RESULTS: A total of 51,842 patients including 45,540 (87.8%) cases of SCC and
6302 (12.2%) of ACA were analyzed. Compared with the ACA patients, the SCC
patients were younger and more frequently black and had a higher degree of
illiteracy and alcohol and tobacco consumers. The tumor stage at the time of
diagnosis was also significantly different between the two groups. However,
initial therapeutic response and death rate after the first course of treatment
were similar in both groups. CONCLUSIONS: Differences between ACA and SCC were
observed for all demographic and clinical variables analyzed but not for
responses to treatment and death at the end of the first course of treatment.
Irrespective of the histological subtype, the quality of screening and treatment
must be improved in developing countries, since initial therapeutic response of
ACA and SCC is similar.
PMID- 25130678
TI - In a randomized, double-blind clinical trial, adjuvant atorvastatin improved
symptoms of depression and blood lipid values in patients suffering from severe
major depressive disorder.
AB - BACKGROUND: The administration of statins seems to be a promising new avenue in
the treatment of patients suffering from major depressive disorder (MDD), though
patients suffering from severe MDD remain unstudied in this respect. The aim of
the present study was therefore to investigate, in a randomized double-blind
clinical trial, the influence of adjuvant atorvastatin on symptoms of depression
in patients with MDD. METHODS: A total of 60 patients suffering from MDD (mean
age: 32.25 years; 53% males) received a standard medication of 40 mg/d
citalopram. Next, patients were randomly assigned either to the atorvastatin
group (20 mg/d) or to the placebo group. Blood lipid values were assessed at
baseline and on completion of the study 12 weeks later. Experts rated depressive
symptoms via Hamilton Depression Rating Scales (HDRS) at baseline and 3, 6 and 12
weeks later. RESULTS: HDRS scores decreased over time; the significant Time by
Group interaction showed that symptoms of depression decreased more in the
atorvastatin than in the placebo group. Compared to the placebo group, in the
atorvastatin group cholesterol, triglyceride, and Low Density Lipids (LDL)
significantly decreased, and High Density Lipids (HDL) significantly increased
over time. HDRS scores and blood lipid values were generally not associated.
CONCLUSIONS: The pattern of results suggests that adjuvant atorvastatin favorably
influences symptoms of depression among patients with severe MDD. Given that
after 12 weeks of monotherapy and adjuvant atorvastatin patients were still
moderately to severely depressed, more powerful treatment algorithms such as
augmentation and change of medication are highly recommended.
PMID- 25130679
TI - The growing epidemic of water pipe smoking: health effects and future needs.
AB - Water pipe smoking (WPS), an old method of tobacco smoking, is re-gaining
widespread popularity all over the world and among various populations. Smoking
machine studies have shown that the water pipe (WP) mainstream smoke (MSS)
contains a wide array of chemical substances, many of which are highly toxic and
carcinogenic for humans. The concentrations of some substances exceed those
present in MSS of cigarettes. Despite being of low grade, current evidence
indicates that WPS is associated with different adverse health effects, not only
on the respiratory system but also on the cardiovascular, hematological, and
reproductive systems, including pregnancy outcomes. In addition, association
between WPS and malignancies, such as lung, oral and nasopharyngeal cancer, has
been suggested in different studies and systematic reviews. Despite its long
standing history, WPS research still harbors a lot of deficiencies. The magnitude
of toxicants and carcinogen exposures, effects on human health, as well as the
addiction and dependence potentials associated with WPS need to be studied in
well-designed prospective trials. Unfortunately, many of the tobacco control and
clean indoor policies have exempted water pipes. World wide awareness among the
public, smokers, and policymakers about the potential health effects of WPS is
urgently required. Furthermore, stringent policies and laws that control and ban
WPS in public places, similar to those applied on cigarettes smoking need to be
implemented.
PMID- 25130680
TI - A simple rule to identify patients with chronic obstructive pulmonary disease who
may need treatment reevaluation.
AB - BACKGROUND: A simple rule based on short-acting inhaled beta2-agonist (SABA) use
could identify patients with chronic obstructive pulmonary disease (COPD) at
increased risk of exacerbations and signal the need for maintenance therapy
change, similar to asthma "Rules of Two((r))". METHODS: Associations between SABA
use, COPD exacerbations, and health care costs over 1 year were examined
retrospectively using de-identified patient data from the Optum Research Database
(ORD; N = 56,581) and the Impact National Benchmark Database (IMPACTTM; N =
9423). Nebulized and metered-dose inhaler (MDI) SABA doses were normalized to 2.5
mg and 90 mcg albuterol equivalents, respectively. RESULTS: The GOLD initiative
establishes >=2 exacerbations/year as indicative of increased risk in COPD. We
identified a correlation (p < 0.0001) between 1.5 SABA doses/day and this
frequency of exacerbations. In ORD, patients using >=1.5 versus <1.5 SABA
doses/day experienced significantly more exacerbations: 1.92 (95% confidence
interval [CI], 1.89-1.96) versus 1.36 (95% CI, 1.34-1.38) per patient year (PPY).
Above-threshold use was associated with higher average annual COPD-related costs
(2010 $US): $21,868 (standard deviation [SD], $53,910) versus $11,686 (SD,
$32,707) for nebulized SABA only, $9216 (SD, $30,710) versus $7334 (SD, $24,853)
for MDI SABA only, and $15,806 (SD, $35,260) versus $11,233 (SD, $27,006) for
both nebulized and MDI SABA. IMPACTTM validated these findings. CONCLUSION:
Patients with COPD using >=1.5 SABA doses/day were at increased risk of
exacerbations. Our results suggest a "Rule of 3-2": SABA use >=3 times in 2 days
should be considered a clinical marker for needing treatment reevaluation.
PMID- 25130681
TI - Getting going and letting go: Religiosity fosters opportunity-congruent coping
with work-related uncertainties.
AB - This study investigated how religiosity relates to goal engagement (i.e.,
investing time and effort; overcoming obstacles) and goal disengagement (i.e.,
protecting self-esteem and motivational resources against failure experiences;
distancing from unattainable goals) in coping with perceived work-related
uncertainties (e.g., growing risk of job loss) that arise from current social
change. We hypothesised that religiosity not only expands individuals' capacities
for both engagement and disengagement but also fosters an opportunity-congruent
pattern of engagement and disengagement, promoting engagement especially under
favourable opportunities for goal-striving in the social ecology and facilitating
disengagement especially under unfavourable opportunities. Multilevel analyses in
a sample of N = 2089 Polish adults aged 20-46 years partly supported these
predictions. Religiosity was associated with higher goal engagement, especially
under favourable economic opportunities for goal-striving in the social ecology
(as measured by the regional net migration rate). For disengagement, the results
were more mixed; religiosity was related to higher self-protection independently
of the economic opportunity structure and predicted higher goal-distancing only
under the most unfavourable opportunities. These results suggest that religiosity
can promote different coping strategies under different conditions, fostering a
pattern of opportunity-congruent engagement and, to some extent, disengagement
that is likely to be adaptive.
PMID- 25130682
TI - How can weight-loss app designers' best engage and support users? A qualitative
investigation.
AB - OBJECTIVES: This study explored young adults' experiences of using e-health
internet-based computer or mobile phone applications (apps) and what they valued
about those apps. DESIGN AND METHODS: A qualitative design was used. Semi
structured interviews were conducted with a community sample of 19 young adults
who had used a publicly available phone or internet-based application.
Transcripts were analysed using thematic analysis. RESULTS: Participants valued
an attractive user interface. Structure, ease of use, personalised features and
accessibility (including dual phone-computer access) were all important to
participants and users indicated that continued use depended on these design
features. Many believed that a focus on calorie counting was too limiting. Some
users mentioned behaviour change strategies and known behaviour change techniques
utilised by apps including; self-monitoring, goal setting and behavioural
feedback. Only a few users reported positive changes in physical activity levels.
CONCLUSIONS: Use of particular design features and application of evidence-based
behaviour change techniques could optimise continued use and the effectiveness of
internet/smart phone interventions. Statement of contribution What is already
known on this subject? E-health is increasingly used to deliver weight
loss/control programs. Most e-health programs have not been founded on evidence
based designs and it is unclear what features and functions users find useful or
not so useful. What does this study add? Weight loss app users valued structure,
ease of use, personalised features and accessibility. Goal setting and feedback
on calorie intake/energy balance were the most widely used behaviour change
techniques. Designers should consider an extensive food database, a food scanner,
and provision of diaries.
PMID- 25130683
TI - Expression of costimulatory molecule B7-H3 and its prognostic implications in
human acute leukemia.
AB - OBJECTIVES: This study focused on the expression pattern and clinical
significance of B7-H3 expression in human acute leukemia. METHODS: We
systematically analyzed 134 patients with acute myeloid leukemia (101 cases) and
acute lymphocytic leukemia (33 cases) by flow cytometry. RESULTS: The frequency
of B7-H3(+) cases was 44.8% in total. The B7-H3 expression rate differed from 0%
to 74.8% in individual cases. The correlation between B7-H3 expression and
traditional prognostic factors, such as age and gender, the white blood cell
count was not confirmed. However, B7-H3 had a significant higher expression in
CD34(+) cases and high risk karyotypes. CONCLUSIONS: Owing to the expression of
B7-H3 being statistically relevant in predicting disease progression and a
shorter life survival, our results demonstrated that B7-H3 expression in acute
leukemia predicts an unfavorable outcome.
PMID- 25130685
TI - Nutrition of the captive western lowland gorilla (Gorilla gorilla gorilla): a
dietary survey.
AB - The successful management of captive animals requires attention to multiple
interconnected factors. One critical aspect of the daily life of a captive animal
is the recommended and/or provisioned diet. This study focuses on the diets of
zoo-housed gorillas. A national survey of diets among zoo-housed gorillas was
conducted to examine diets being offered to captive gorillas in the United States
and Canada. This survey serves as a follow-up to a 1995 dietary survey of zoo
housed gorillas and goes further to quantify nutritional profiles at responding
institutions. Results are encouraging, as zoos have made clear improvements in
dietary nutrient profiles offered over the past 15 years. However, we suggest
that zoological and sanctuary institutions follow Gorilla Species Survival Plan
(SSP) recommendations and work to continuously improve diets provided, which
could improve gorillas' health and well-being.
PMID- 25130684
TI - Gestational diabetes mellitus modulates neonatal high-density lipoprotein
composition and its functional heterogeneity.
AB - Gestational diabetes mellitus (GDM) is related to neonatal macrosomia and an
increased risk of vascular events. We hypothesized that GDM exerts qualitative
effects on neonatal high-density lipoprotein (HDL). HDL was isolated from control
(n=11) and GDM maternal/neonatal donors (n=9) and subjected to shotgun
proteomics. Differences in HDL mobility were assessed by FPLC and native gel
electrophoresis. Paraoxonase (PON1) activity, cholesterol ester-transfer protein
(CETP) mass and activity, phospholipid, triglyceride and cholesterol
concentrations were quantified with commercial kits. Total anti-oxidative
capacity and cholesterol efflux capability of HDLs were measured. Four proteins
involved in lipid metabolism, inflammation and innate immunity were
differentially expressed between controls and GDM neonates. ApoM (decreased,
p<0.05) and SAA1 (increased, p<0.05) showed the same differences on both,
maternal and neonatal GDM HDL. Lower PON1 protein expression was corroborated by
lower activity (p<0.05) which in turn was associated with attenuated anti-oxidant
capacity of GDM HDL. Protein changes were accompanied by increased levels of
triglycerides and decreased levels of cholesterol esters, respectively. The
observed differences in GDM HDL lipid moiety may be related to CETP mass and
activity alterations. The rate of cholesterol efflux from term trophoblasts to
maternal and from placental endothelial cells to neonatal GDM HDL was impaired
(p<0.05). In conclusion, GDM causes changes in HDL composition and is intimately
associated with impaired cholesterol efflux capability as well as diminished anti
oxidative particle properties. Remodeling of neonatal GDM HDL in utero supports
the hypothesis that maternal conditions in pregnancy impact neonatal lipoprotein
metabolism.
PMID- 25130687
TI - The social media revolution is changing the conference experience: analytics and
trends from eight international meetings.
AB - OBJECTIVE: To analyse the use of Twitter at urology conferences to enhance the
social media conference experience. MATERIALS AND METHODS: We prospectively
registered the hashtags of eight international urology conferences taking place
in 2013, using the social media metrics website, Symplur.com. In addition, we
prospectively registered the hashtag for the European Association of Urology
(EAU) Annual Congress for 3 consecutive years (2012-2014) to analyse the trend in
the use of Twitter at a particular meeting. Metrics including number of 'tweets',
number of participants, tweet traffic per day, and overall digital impressions,
which were captured for 5 days before each conference, the conference itself, and
the following 2 days. We also measured corresponding social media activity at a
very large non-urology meeting (the American Society of Clinical Oncology) for
comparative purposes. RESULTS: Twitter activity was noted at all eight
conferences in 2013. In all, 12,363 tweets were sent generating over 14 million
impressions. The number of participants tweeting at each meeting varied from 80
(Congress of the Societe Internationale d'Urologie, #SIU2013) to 573 (the
American Urological Association, #AUA13). Overall, the AUA meeting (#AUA13)
generated the most Twitter activity with >8.6 million impressions and a total of
4663 tweets over the peri-conference period. It also had the most impressions and
tweets per day over this period, at 717,000 and 389, respectively. The EAU Annual
Congress 2013 (#EAU13) generated 1.74 million impressions from a total of 1762
tweets from 236 participants. For trends in Twitter use, there was a very sharp
rise in Twitter activity at the EAU Annual Congress between 2012 and 2014. Over
this 3-year period, the number of participants increased almost 10-fold, leading
to an increase in the number of tweets from 347 to almost 6000. At #EAU14,
digital impressions reached 7.35 million with 5903 tweets sent by 797
participants. CONCLUSIONS: Urological conferences, to a varying extent, have
adopted social media as a means of amplifying the conference experience to a
wider audience, generating international engagement and global reach. Twitter is
a very powerful tool that amplifies the content of scientific meetings, and
conference organisers should put in place strategies to capitalise on this.
PMID- 25130686
TI - Migration and differentiation of gonadal germ cells under cross-sex germline
chimeras condition in domestic chickens.
AB - A series of experiments was conducted to investigate migration, proliferation and
differentiation of gonadal germ cells (GGCs) collected from the gonads of 7-day
old chick embryos under cross-sex germline chimera conditions. The migratory and
proliferative abilities of exogenous GGCs were examined by transferring 50
fluorescently labeled GGCs collected from White Leghorn (WL) embryos into the
blood of 2-day-old Rhode Island Red (RIR) embryos. No significant difference was
observed in the number of fluorescently labeled GGCs in the gonads of recipient
embryos among any of the four possible donor and recipient sex combinations.
Cross-sex germline chimeras were produced to examine the differentiation of GGCs
by transferring 100 GGCs from WL embryos into 2-day-old RIR embryos. Exogenous
GGC-derived progeny were obtained from both male and female recipients, except
when female GGCs were transferred into male recipients. The migratory ability of
GGCs recovered from the 7-day-old embryonic gonad was not influenced by cross-sex
germ cell transfer conditions, whereas the differentiation of the GGCs was
affected by the sex combinations of GGCs donors and recipients.
PMID- 25130688
TI - Prognostic factors in adolescent and adult patients with acute lymphoblastic
leukemia with two protocols of chemotherapy: a cross-sectional study.
AB - BACKGROUND: We evaluated the clinical, laboratory, and prognostic factors in
adolescent and adult patients with acute lymphoblastic leukemia (ALL). MATERIALS
AND METHODS: In this observational, retrospective, cross-sectional study, we
examined the medical records of all consecutive patients with ALL admitted to a
public hospital in Brazil from 1990 to 2005. RESULTS: Of the 102 patients
included, 88 were treated with 2 protocols of chemotherapy (Berlin-Frankfurt
Munster [BFM] 86 modified [BFM-86M] and UCLA [University of California, Los
Angeles] protocol). The complete remission (CR), disease-free survival, and
overall survival (OS) rate was 70.6%, 27%, and 30.5%, respectively (median follow
up, 49 months). Age < 18 years and no leukemic infiltration in the central
nervous system (CNS) at diagnosis were positively associated with CR (P = .03);
no bleeding and hepatomegaly at diagnosis and age < 35 years were associated with
better OS on multivariate analyses of the whole population (P = .01). OS at 4
years was superior with BFM-86M than with UCLA (49.5% vs. 16%; P = .004),
especially in young adults without risk factors. CONCLUSION: We identified age as
the most important prognostic factor in patients with ALL. CNS infiltration,
hepatomegaly, and bleeding were associated with lower OS but must be validated in
future research with South American populations and worldwide. The BFM-86M
protocol can be considered a therapeutic option for young adults (age < 35 years)
without adverse prognostic factors. For other patients with ALL, we emphasize the
need for different therapeutic approaches.
PMID- 25130689
TI - An orthogonal click-chemistry approach to design poly(glycerol monomethacrylate)
based nanomaterials for controlled immunostimulation.
AB - A versatile approach is proposed for the synthesis of novel immunoactive
nanomaterials based on biocompatible poly(glycerol monomethacrylate) (PGMMA).
Propargyl-terminated PGMMA is synthesized via atom transfer radical
polymerization and then modified through the introduction of dangling acrylate
groups, at controlled degree of functionalisation. Acrylates are then able to
react quantitatively with thiols, such as immunoactive thiomannose, through
Michael-type addition under mild conditions and at a physiologically acceptable
pH. The terminal propargyl group can be modified independently with azide end
capping groups and it is utilized to graft the macromolecules to a fluorescent
dye. The resulting mannose-linked PGMMAs confirm a safe cytotoxic profile and are
able to stimulate cytokine production (TNFalpha), membrane protein expression
(CD40), and cellular uptake in bone marrow derived dendritic cells. Cell
stimulation is dependent on the mannose content and enhanced by serum proteins,
suggesting a role for mannose-binding receptors and/or complement receptors in
the cell membrane.
PMID- 25130693
TI - The biology of Mur ligases as an antibacterial target.
AB - With antibiotic resistance mechanisms increasing in diversity and spreading among
bacterial pathogens, the development of new classes of antibacterial agents
against judiciously chosen targets is a high-priority task. The biochemical
pathway for peptidoglycan biosynthesis is one of the best sources of
antibacterial targets. Within this pathway are the Mur ligases, described in this
review as highly suitable targets for the development of new classes of
antibacterial agents. The amide ligases MurC, MurD, MurE and MurF function with
the same catalytic mechanism and share conserved amino acid regions and
structural features that can conceivably be exploited for the design of
inhibitors that simultaneously target more than one enzyme. This would provide
multi-target antibacterial weapons with minimized likelihood of target-mediated
resistance development.
PMID- 25130694
TI - Hibernation alters the diversity and composition of mucosa-associated bacteria
while enhancing antimicrobial defence in the gut of 13-lined ground squirrels.
AB - The gut microbiota plays important roles in animal nutrition and health. This
relationship is particularly dynamic in hibernating mammals where fasting drives
the gut community to rely on host-derived nutrients instead of exogenous
substrates. We used 16S rRNA pyrosequencing and caecal tissue protein analysis to
investigate the effects of hibernation on the mucosa-associated bacterial
microbiota and host responses in 13-lined ground squirrels. The mucosal
microbiota was less diverse in winter hibernators than in actively feeding spring
and summer squirrels. UniFrac analysis revealed distinct summer and late winter
microbiota clusters, while spring and early winter clusters overlapped slightly,
consistent with their transitional structures. Communities in all seasons were
dominated by Firmicutes and Bacteroidetes, with lesser contributions from
Proteobacteria, Verrucomicrobia, Tenericutes and Actinobacteria. Hibernators had
lower relative abundances of Firmicutes, which include genera that prefer plant
polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some
of which can survive solely on host-derived mucins. A core mucosal assemblage of
nine operational taxonomic units shared among all individuals was identified with
an average total sequence abundance of 60.2%. This core community, together with
moderate shifts in specific taxa, indicates that the mucosal microbiota remains
relatively stable over the annual cycle yet responds to substrate changes while
potentially serving as a pool for 'seeding' the microbiota once exogenous
substrates return in spring. Relative to summer, hibernation reduced caecal crypt
length and increased MUC2 expression in early winter and spring. Hibernation also
decreased caecal TLR4 and increased TLR5 expression, suggesting a protective
response that minimizes inflammation.
PMID- 25130696
TI - A novel method for autograft placement during tegmen repair: the suture "pull
through" technique.
PMID- 25130695
TI - Sequential gene silencing using wavelength-selective caged morpholino
oligonucleotides.
AB - Spectrally differentiated caged morpholino oligonucleotides (cMOs) and wavelength
selective illumination have been used to sequentially inactivate organismal gene
function. The efficacy of these reverse-genetic chemical probes has been
demonstrated in zebrafish embryos, and these reagents have been employed to
examine the mechanisms of mesoderm patterning.
PMID- 25130697
TI - Residence-time dependent cell wall deformation of different Staphylococcus aureus
strains on gold measured using surface-enhanced-fluorescence.
AB - Bacterial adhesion to surfaces is accompanied by cell wall deformation that may
extend to the lipid membrane with an impact on the antimicrobial susceptibility
of the organisms. Nanoscale cell wall deformation upon adhesion is difficult to
measure, except for Deltapbp4 mutants, deficient in peptidoglycan cross-linking.
This work explores surface enhanced fluorescence to measure the cell wall
deformation of Staphylococci adhering on gold surfaces. Adhesion-related
fluorescence enhancement depends on the distance of the bacteria from the surface
and the residence-time of the adhering bacteria. A model is forwarded based on
the adhesion-related fluorescence enhancement of green-fluorescent microspheres,
through which the distance to the surface and cell wall deformation of adhering
bacteria can be calculated from their residence-time dependent adhesion-related
fluorescence enhancement. The distances between adhering bacteria and a surface,
including compression of their extracellular polymeric substance (EPS)-layer,
decrease up to 60 min after adhesion, followed by cell wall deformation. Cell
wall deformation is independent of the integrity of the EPS-layer and proceeds
fastest for a Deltapbp4 strain.
PMID- 25130699
TI - Abstracts of the SMART STROKES 2014 Conference, 28-29 August, 2014, Sydney, NSW,
Australia.
PMID- 25130698
TI - miR-639 regulates transforming growth factor beta-induced epithelial-mesenchymal
transition in human tongue cancer cells by targeting FOXC1.
AB - Epithelial-to-mesenchymal transition (EMT) is implicated in embryonic development
and various pathological events. Transforming growth factor beta (TGFbeta) has
been reported to induce EMT in tumor cells, which is a critical step in the
process of metastasis leading to cancer spreading and treatment failure. However,
the involvement of microRNA during the EMT process in tongue squamous cell
carcinoma (TSCC) remains to be determined. To address this question, TSCC cell
lines SCC9 and CAL27 were treated with human recombinant TGFbeta1 for 48 h. miRNA
microarray illustrated that miR-639 was significantly downregulated in TGFbeta
treated SCC9 cells. Ectopic expression of miR-639 with miRNA mimics effectively
blocked TGFbeta-induced EMT in SCC9 and CAL27 cells, but inhibition of miR-639 in
SCC9 and CAL27 cells with antisense oligonucleotides induced EMT. Computational
microRNA target predictions detected a conserved sequence matching to the seed
region of miR-639 in the 3'-UTR of FOXC1 mRNA. Luciferase reporter assays
revealed that miR-639 targets FOXC1. Ectopic expression of FOXC1 induces EMT in
TSCC cells. Silencing FOXC1 expression blocked TGFbeta-induced EMT in SCC9 cells.
Clinically, reduced miR-639 expression was associated with metastasis in TSCC and
poor patient survival. The data from the present study suggest that reduced
expression of miR-639 underscores the mechanism of TGFbeta-induced EMT in TSCC by
targeting FOXC1 and may serve as therapeutic targets in the process of
metastasis.
PMID- 25130700
TI - Functionalization of cantilever tips with nucleotides by the phosphoramidite
method.
AB - In atomic force microscopy (AFM) a sharp cantilever tip is used to scan surfaces
at the atomic level. One further application is force spectroscopy, in which
force-distance curves between binding partners located on the cantilever and
substrate surface are determined. This requires specifically immobilized
molecules. Herein we describe the covalent binding of single adenosine and
thymidine nucleotides on an amino-PEGylated cantilever tip by the phosphoramidite
method. Force-distance curves between these cantilever tips and gold surfaces
were recorded. The rupture forces of the coordination bond between the primary
amine of adenosine and the undercoordinated gold atoms were determined to be 145
pN, which is in agreement with previously published data. The force-distance
curves of thymidine-functionalized tips did not show rupture events, because this
nucleotide does not possess a primary amine function. Nucleotide-functionalized
tips could aid in the understanding of binding mechanisms of nucleotide binding
molecules such as polymerases immobilized on surfaces or membranes.
PMID- 25130702
TI - Marker genes for the metabolic adaptation of Pseudomonas aeruginosa to the
hypoxic cystic fibrosis lung environment.
AB - Pseudomonas aeruginosa is the leading pathogen of chronic cystic fibrosis (CF)
lung infection. Life-long persistence in the inflamed and ever fluctuating CF
lungs results in the selection of a variety of changes in P. aeruginosa
physiology. Accumulating evidence suggests that especially metabolic changes
support the survival and growth of P. aeruginosa within the hypoxic and
nutritious CF mucus. To investigate if metabolic adaptations we described for
hypermutable P. aeruginosa from late CF lung disease (Hoboth et al., 2009. J.
Infect. Dis., pp. 118-130) may represent specific changes in response to the
selective conditions within the oxygen-restricted CF mucus, we determined the
expression of a set of genes during aerobic and hypoxic growth in LB and the
artificial sputum medium ASM. We further focused on the regulation of the two
isocitrate dehydrogenases Icd and Idh. Interestingly, both isoenzymes may replace
each other under aerobic and hypoxic conditions. The NADPH- and RpoS-dependent
Icd seems to be the leading isoenzyme under prolonged oxygen limitation and
stationary growth phase. LacZ reporter analysis revealed that oxygen-restriction
increased the expression levels of azu, cbb3-1, cbb3-2, ccpR, icd, idh and oprF
gene, whereas himD and nuoA are increasingly expressed only during hypoxic growth
in ASM. Overexpression of the anaerobic regulator Anr improved the expression of
azu, ccpR, cbb3-2 and icd. In summary, expression of azu, cbb3-1, cbb3-2, ccpR,
icd, idh, oprF, himD, and nuoA appeared to be beneficial for the growth of P.
aeruginosa under hypoxic conditions indicating these genes may represent marker
genes for the metabolic adaptation to the CF lung environment.
PMID- 25130703
TI - Risk factors for MRSA infection in companion animals: results from a case-control
study within Germany.
AB - Increasing numbers of companion animals suffering from infections with
methicillin-resistant Staphylococcus aureus (MRSA) have been reported in the
recent past. These infections are of particular concern because of the limited
treatment options for MRSA and their transferability to humans. Since MRSA
lineages isolated from infected companion animals often mirror typical human
epidemic strains circulating in the same region, successful strategies to combat
MRSA need strong and coordinated efforts from both, the human and the veterinary
field according to the "One Health" concept. Hence, to identify potential risk
factors related to MRSA infections in dogs, cats and horses, a case-control study
was conducted, including data on 106 MRSA-infected animal patients as cases and
102 MSSA-infected animals as controls, originating from 155 different veterinary
settings within Germany. Demographic data on animal patients, patient history and
administration of antibiotics as well as practice/clinic specific parameters were
assessed as putative risk factors. Multivariable logistic regression identified
the following variables as risk factors for MRSA infection compared to MSSA
infection: number of employees working at the veterinary setting (n>10; p<0.001),
antibiotic treatment prior to sampling (systemic: p=0.002; local: p=0.049, both:
p=0.011) and surgical site infection (p<0.001). Spa typing revealed predominantly
clonal complexes well-known for hospital-associated lineages spreading in human
health-care settings in Germany (CC5 and CC22) for isolates of dog and cat
origin. CC398-MRSA dominated among equine isolates, a CC that was described as a
nosocomial pathogen in equine clinical settings before. The identified risk
factors and genotyping results are in accordance with numerous study outcomes
from the field of human medicine and point towards reasonable problems with
nosocomial spread of MRSA, especially within companion animal veterinary clinics.
To define targeted infection control strategies against nosocomial pathogens, it
is important to accomplish intervention studies addressing routes of transmission
in companion animal veterinary settings.
PMID- 25130701
TI - The effects of the pharmaceutical carbamazepine on life history characteristics
of flat-headed mayflies (Heptageniidae) and aquatic resource interactions.
AB - Pharmaceutical pollutants are commonly detected in freshwater ecosystems around
the world and have biological effects on aquatic organisms. However, current
understanding of the influence this contaminant class has on freshwater
communities and ecosystems is lacking. Recently the scientific community has
called for research focusing on certain pharmaceuticals due to their ubiquity and
potential toxicity. Carbamazepine is one of these pharmaceuticals. To better
understand the effect carbamazepine has on life history characteristics of
aquatic organisms and consumer-resource interactions, we quantified the influence
of carbamazepine on the development, growth and behavior of mayfly nymphs
(Stenonema sp.) and the alterations in food consumer-resource interactions
between Stenonema and algae (Chaetophora). Microcosms were assembled in a
factorial design containing algae and mayfly nymphs native to central Indiana and
dosed with environmentally relevant concentrations of carbamazepine. From this
ecotoxicological experiment we were able to infer that carbamazepine at 2,000
ng/L influenced the development and behavior of Stenonema nymphs and the body
dimensions of adult individuals. However, it appears that carbamazepine does not
influence consumer-resource interactions at concentrations found in surface
waters. The pharmaceutical carbamazepine may influence the behavior, growth and
development of mayflies, which could have significant consequences at the
population, community and ecosystem level.
PMID- 25130704
TI - Cost-effectiveness of red blood cell transfusion vs. non-intervention in women
with acute anaemia after postpartum haemorrhage.
AB - BACKGROUND: Red blood cell (RBC) transfusion is frequently used to treat women
with acute anaemia after postpartum haemorrhage. We aimed to assess the economic
consequences of red blood cell transfusion compared to non-intervention in these
women. METHODS: A trial-based cost-effectiveness analysis was performed alongside
the Well-Being of Obstetric patients on Minimal Blood transfusions (WOMB) trial.
Women with acute anaemia [Hb 4.8-7.9 g/dl (3.0-4.9 mm)] after postpartum
haemorrhage, without severe anaemic symptoms, were randomly allocated to RBC
transfusion or non-intervention. Primary outcome of the trial was physical
fatigue (Multidimensional Fatigue Inventory, scale 4-20; 20 represents maximal
fatigue). Total costs per arm were calculated using a hospital perspective with a
6 weeks time horizon. RESULTS: Per woman, mean costs in the RBC transfusion arm
(n = 258) were ?1957 compared to ?1708 in the non-intervention arm (n = 261; P =
0.024). The 13% difference in costs between study arms predominantly originated
from costs of RBC units, as costs of RBC units were six times higher in the RBC
transfusion arm. RBC transfusion led to a small improvement in physical fatigue
of 0.58 points per day; thus, the costs to improve the physical fatigue score
with one point would be ?431. CONCLUSION: In women with acute anaemia after
postpartum haemorrhage (PPH), RBC transfusion is on average ?249 more expensive
per woman than non-intervention, with only a small gain in HRQoL after RBC
transfusion. Taking both clinical and economic consequences into account,
implementation of a non-intervention policy seems justified.
PMID- 25130706
TI - Exchange-coupled nanocomposites: chemical synthesis, characterization and
applications.
AB - Nanocomposites containing soft and hard magnetic phases have attracted immense
attention for energy-related and biomedical applications. With exchange coupling
between nanoscale grains in the composites, magnetization of the soft magnetic
phase can rotate coherently with that of the hard magnetic phase. In particular,
good control of the soft and hard phases at the nanoscale in the composites is of
great importance for effective exchange coupling, allowing us to make the best of
the strengths of soft and hard magnetic phases and to optimize the magnetic
properties for targeted applications. In this review, we present the recent
progress in the chemical synthesis and applications of exchange-coupled
nanocomposites. Firstly, the principle of nanomagnetism and exchange coupling is
introduced. Secondly, the characterization of exchange-coupled nanocomposites is
summarized. Thirdly, the chemical methods for the production of different
exchange-coupled nanocomposites are presented. Finally, applications of exchange
coupled nanocomposites in magnetic energy storage and biomedicine are addressed.
PMID- 25130705
TI - Minimally invasive fetal autopsy using ultrasound: a feasibility study.
AB - OBJECTIVES: To evaluate postmortem ultrasound (PM-US) for minimally invasive
autopsy, and to demonstrate its feasibility, sensitivity and specificity, as
compared with conventional autopsy, in detecting major congenital abnormalities.
METHODS: Over a 19-month study period from 1 March 2012 to 30 September 2013, we
recruited from a referral hospital 88 consecutive fetuses, at 11-40 weeks'
gestation, which had undergone termination, miscarriage or intrauterine fetal
death. We performed PM-US using different transducers and compared the data with
those from conventional autopsy. The latter was performed, according to the
Societe Francaise de Foetopathologie (France) guidelines, by experienced
perinatal pathologists who were blinded to the ultrasound data. RESULTS: Complete
virtual autopsy by ultrasound was possible in 95.5% of the cases. The sensitivity
of PM-US for detecting brain abnormalities was 90.9% (95% CI, 58.7-99.8%) and the
specificity was 87.3% (95% CI, 75.5-94.7%). In 20% of cases, a neuropathological
examination was not possible due to severe maceration. The sensitivity for
detection of thoracic abnormalities was 88.9% (95% CI, 65.3-98.6%) and the
specificity was 92.8% (95% CI, 84.1-97.6%), and the sensitivity for detection of
abdominal anomalies was 85.7% (95% CI, 57.2-98.2%) and the specificity was 94.6%
(95% CI, 86.7-98.5%). CONCLUSION: This pilot study confirms the feasibility of PM
US for virtual autopsy as early as 11 weeks' gestation. This new technique shows
high sensitivity and specificity in detecting congenital structural abnormalities
as compared with conventional autopsy. Copyright (c) 2014 ISUOG. Published by
John Wiley & Sons Ltd.
PMID- 25130707
TI - Predictors of men's sexual response to erotic film stimuli: the role of affect
and self-reported thoughts.
AB - INTRODUCTION: Both emotions and cognitions seem to play a role in determining
sexual arousal. However, no studies to date have tested the effects of self
reported thoughts on subjective sexual arousal and genital response using
psychophysiological methods. AIM: The aim of the present study was to evaluate
the role of self-reported thoughts and affect during exposure to erotic material
in predicting subjective and genital responses in sexually healthy men. METHODS:
Twenty-seven men were presented with two explicit films, and genital responses,
subjective sexual arousal, self-reported thoughts, and positive and negative
affect were assessed. MAIN OUTCOME MEASURES: Men's genital responses, subjective
sexual arousal, affective responses, and self-reported thoughts during exposure
to sexual stimulus were measured. RESULTS: Regression analyses revealed that
genital responses were predicted by self-reported thoughts (explaining 20% of the
variance) but not by affect during exposure to erotic films. On the other hand,
subjective sexual arousal was significantly predicted by both positive and
negative affect (explaining 18% of the variance) and self-reported thoughts
(explaining 37% of the variance). Follow-up analyses using the single predictors
showed that "sexual arousal thoughts" were the only significant predictor of
subjective response (beta = 0.64; P < 0.01) and that "distracting/disengaging
thoughts" were the best predictor of genital response (beta = -0.51; P < 0.05).
CONCLUSIONS: The findings of this study suggest that both affect and sexual
arousal thoughts play an important role in men's subjective sexual response,
whereas genital response seems to be better predicted by distracting thoughts.
PMID- 25130708
TI - Nanotube aerogel sheet flutter for actuation, power generation, and infrasound
detection.
AB - Electromagnetic induction (EMI) is a mechanism of classical physics that can be
utilized to convert mechanical energy to electrical energy or electrical to
mechanical energy. This mechanism has not been exploited fully because of lack of
a material with a sufficiently low force constant. We here show that carbon
nanotube (CNT) aerogel sheets can exploit EMI to provide mechanical actuation at
very low applied voltages, to harvest mechanical energy from small air pressure
fluctuations, and to detect infrasound at inaudible frequencies below 20 Hz.
Using conformal deposition of 100 nm thick aluminum coatings on the nanotubes in
the sheets, mechanical actuation can be obtained by applying millivolts, as
compared with the thousand volts needed to achieve giant-stroke electrostatic
actuation of carbon nanotube aerogel sheets. Device simplicity and performance
suggest possible applications as an energy harvester of low energy air
fluctuations and as a sensor for infrasound frequencies.
PMID- 25130709
TI - Simultaneous KIT mutation and succinate dehydrogenase (SDH) deficiency in a
patient with a gastrointestinal stromal tumour and Carney-Stratakis syndrome: a
case report.
PMID- 25130710
TI - Prediction of the net energy value of broiler diets.
AB - Thirty pelleted diets were given to broiler chickens (eight birds per diet; 21 to
35 days of age) for individual in vivo measurements of dietary net energy (NE)
value, using three trials with 10 diets/trial. Amino acid formulation of diets
was done on the basis of ratios to CP. NE was measured according to the body
analysis method. The basal metabolism component of NE values was calculated on
the basis of mean metabolic weight using a coefficient obtained in a previous
experiment. Information about apparent metabolisable energy (AME) value of diets,
AME corrected to zero nitrogen retention (AMEn) and digestibilities of proteins,
lipids, starch and sugars was available from a previous publication. In each
trial, mean NE/AME ratios of diets varied by about 6%. From the multiple
regressions (n=30) expressing NE and AMEn values as functions of digestible
component contents, it was deduced that the NE/AMEn ratios assigned to dietary
components were 0.760, 0.862, 0.806, 0.690 and 0.602 for CP, lipids, starch,
(sucrose+glucose) and fermentable sugars (alpha-galacto-oligosaccharides and
lactose), respectively. The NE/AME ratio of CP was 0.680. Regression calculations
showed that the NE values assigned to individual birds (n=240) could also be
predicted with diet AMEn values (NE=0.80 AMEn; R 2=0.770) or with an equation
combining AMEn value and CP/AMEn ratio (R 2=0.773). The latter ratio was found to
be the only additional parameter that was significant when added in the NE
regression scheme based on AMEn.
PMID- 25130711
TI - Changes in plasma leptin concentration during different types of exercises
performed by horses.
AB - Leptin is a tissue-derivative adipokine that regulates appetite, food intake and
energy expenditure. It is still not clear how exercise affects plasma leptin
concentration in horses. The aim of this study was to evaluate the influence of
exercise intensity and duration on plasma leptin levels in working horses. A
total of 38 horses were prospectively included in the study and grouped according
to the type of exercise they performed: dressage (six stallions, group D),
jumping (12 stallions, group J), race (12 Thoroughbred horses, six stallions and
six mares, group R) and harness (10 light draft stallions, group H). Blood
samples were taken both before and after routine exercise (immediately after the
exercise, 30 min and 24 h after). Blood lactic acid (LA) and plasma concentration
of leptin, cortisol, uric acid, triacylglycerols, glycerol and free fatty acids
were determined. Immediately after exercise, group R had the highest level of LA,
whereas groups D and J had the lowest levels. A significant increase in plasma
leptin concentration was stated only in group H in samples taken immediately
after the end of the exercise period and 30 min after the exercise period, as
compared with the values obtained at rest. A significant increase in plasma
cortisol concentration was found immediately after the end of the exercise period
in groups R and H. Leptin exercise-to-rest ratio was significantly correlated
with cortisol exercise-to-rest ratio (r=0.64; P<0.001). The increase in plasma
leptin concentration in exercised horses was related to the increased plasma
cortisol concentration and took place only during long-lasting exercise, which
was not intensive.
PMID- 25130712
TI - Injurious tail biting in pigs: how can it be controlled in existing systems
without tail docking?
AB - Tail biting is a serious animal welfare and economic problem in pig production.
Tail docking, which reduces but does not eliminate tail biting, remains
widespread. However, in the EU tail docking may not be used routinely, and some
'alternative' forms of pig production and certain countries do not allow tail
docking at all. Against this background, using a novel approach focusing on
research where tail injuries were quantified, we review the measures that can be
used to control tail biting in pigs without tail docking. Using this strict
criterion, there was good evidence that manipulable substrates and feeder space
affect damaging tail biting. Only epidemiological evidence was available for
effects of temperature and season, and the effect of stocking density was
unclear. Studies suggest that group size has little effect, and the effects of
nutrition, disease and breed require further investigation. The review identifies
a number of knowledge gaps and promising avenues for future research into
prevention and mitigation. We illustrate the diversity of hypotheses concerning
how different proposed risk factors might increase tail biting through their
effect on each other or on the proposed underlying processes of tail biting. A
quantitative comparison of the efficacy of different methods of provision of
manipulable materials, and a review of current practices in countries and
assurance schemes where tail docking is banned, both suggest that daily provision
of small quantities of destructible, manipulable natural materials can be of
considerable benefit. Further comparative research is needed into materials, such
as ropes, which are compatible with slatted floors. Also, materials which double
as fuel for anaerobic digesters could be utilised. As well as optimising housing
and management to reduce risk, it is important to detect and treat tail biting as
soon as it occurs. Early warning signs before the first bloody tails appear, such
as pigs holding their tails tucked under, could in future be automatically
detected using precision livestock farming methods enabling earlier reaction and
prevention of tail damage. However, there is a lack of scientific studies on how
best to respond to outbreaks: the effectiveness of, for example, removing biters
and/or bitten pigs, increasing enrichment, or applying substances to tails should
be investigated. Finally, some breeding companies are exploring options for
reducing the genetic propensity to tail bite. If these various approaches to
reduce tail biting are implemented we propose that the need for tail docking will
be reduced.
PMID- 25130713
TI - Adolescent Motivations to Engage in Pro-Social Behaviors and Abstain From Health
Risk Behaviors: A Self-Determination Theory Approach.
AB - The present study used self-determination theory to examine adolescents'
motivations to engage in charitable donating and community volunteering and to
abstain from sexual intercourse and marijuana use. The sample consisted of 419
late adolescents recruited from across the country through an online survey
panel. Participants completed online measures of motivations to engage in
donating and volunteering, motivations to abstain from sex and marijuana, and
single-item indexes of the four behaviors. Variable-centered analyses
(correlation and regression) found evidence for a general motivational factor,
motivational specificity by behavioral domain (positive and negative behaviors),
motivational specificity by particular behavior (charitable donating,
volunteering, sexual risk-taking, and marijuana use), and a stronger relative
role for autonomous motivations than controlled motivations. Person-centered
analyses (cluster analysis) found four motivation profiles (low motivation,
medium motivation, high motivation, and mixed motivation) for all four behaviors
and suggested that level of autonomous motivation was a key factor
differentiating the groups on levels of behavior. The findings suggest different
levels of motivational specificity and highlight the importance of autonomous
motivations in predicting behaviors as compared to controlled motivations.
Further, similar patterns were found for motivations to engage and to abstain.
PMID- 25130714
TI - [Thrombosed orbital varix presenting as a subretinal mass].
PMID- 25130715
TI - Cognitive and neuroprotective effects of chlorogenic acid.
AB - OBJECTIVES: The aim of this review was to provide an overview of studies
conducted to determine the effects of chlorogenic acid (CGA) on cognition and
neurological health. METHODS: A literature search was conducted using PubMed and
various search terms including chlorogenic acid, CGA, memory, neuroscience,
cognition, nutrition, antioxidant, pharmacokinetics, neuroprotection, and
neurodegeneration. RESULTS: Many studies have linked CGA consumption to a wide
range of health benefits, including neuroprotection, cardioprotection, weight
loss, chemopreventive properties, anti-inflammatory activity, decreased blood
pressure, decreased diet-induced insulin resistance, decreased blood pressure,
anxiolytic effects, and antihyperalgesic effects. Pre-clinical and clinical
studies both provide evidence that CGA supplementation could protect against
neurological degeneration and the resulting diseases associated with oxidative
stress in the brain; however, no formal, well-controlled studies have been
performed to date. DISCUSSION: Recent research suggests that dietary consumption
of CGA could produce a wide range of health benefits and physiological effects.
There is also mounting evidence that the consumption of polyphenols, including
CGA, in the diet could reduce the risk of developing neurodegenerative
conditions. Further studies should be conducted with a focus on the effects of
CGA on cognition and the nervous system and employing well-designed clinical
studies.
PMID- 25130716
TI - Genetic, molecular and physiological mechanisms involved in human obesity:
Society for Endocrinology Medal Lecture 2012.
AB - The health consequences of obesity represent one of the major public health
challenges of our time. Whilst the role of environmental drivers such as reduced
physical activity and increased food intake is widely acknowledged, the
importance of biological factors which influence individual variation in weight
is less readily recognised. Considerable evidence suggests that genetic factors
influence a person's weight in a given environment and that these genetic
influences are more potent at the extremes of the body mass index (BMI)
distribution. The discovery that genetic disruption of certain pathways can lead
to severe obesity has informed our current understanding of how body weight is
regulated by brain circuits that regulate appetite and energy expenditure. These
studies provide a framework for investigating patients and ultimately may guide
the development of more rational-targeted therapies for genetically susceptible
individuals with severe obesity.
PMID- 25130717
TI - Stone/tissue differentiation during intracorporeal lithotripsy using diffuse
white light reflectance spectroscopy: In vitro and clinical measurements.
AB - BACKGROUND AND OBJECTIVE: Holmium laser lithotripsy is the 'gold standard' for
intracorporeal fragmentation of stones. However, there is a risk of damaging and
perforating the ureter wall when the laser is accidentally fired while the fiber
is in contact with tissue. The aim of this study was to evaluate if white
illumination light, diffusely reflected back into the treatment fiber and
spectrally analyzed, can be used for differentiating between stone and tissue.
STUDY DESIGN/MATERIALS AND METHODS: Firstly, in vitro reflectance spectra (Xenon
light source, wavelength range lambda = 350-850 nm) of 38 human kidney stones,
porcine renal calix and ureter tissue were collected. Secondly, in an in vivo
study with 8 patients, 72 ureter and 49 stone reflectance signals were recorded
during endourological interventions. The spectra were analyzed to discriminate
between stone and tissue by the absence or presence of minima due to hemoglobin
absorption at lambda1 = 542nm and lambda3 = 576nm. RESULTS: In vitro, all stone
and tissue signals could correctly be identified by calculating the ratio R = I
(lambda1 = 542 nm)/I (lambda2 = 475 nm): Because of the hemoglobin absorption
at lambda1 , R is smaller for tissue than for calculi. In vivo, only 75% tissue
spots could correctly be identified utilizing this method. Using the more
sophisticated evaluation of looking for minima in the diffuse reflectance spectra
at lambda1 = 542 nm and lambda3 = 576 nm, 62 out of 64 tissue spots were
correctly identified (sensitivity 96.9%). This was also the case for 39 out of 43
stone spots. Taking into account the number of measured spectra, a tissue
detection probability of 91% and a stone detection probability of 77% was
achieved (significance level 5%). CONCLUSION: White light diffusely reflected off
the treatment zone into the fiber can be used to strongly improve the safety of
Holmium laser lithotripsy by implementing an automatic feedback control algorithm
that averts mispositioning the fiber.
PMID- 25130718
TI - Family history of psychosis and social, occupational and global outcome in
schizophrenia: a meta-analysis.
AB - OBJECTIVE: We aimed to investigate associations between family history of
psychosis and long-term occupational, social and global (i.e. combined
occupational, social and clinical) outcome in schizophrenia. METHOD: A systematic
search to identify potentially relevant studies was conducted using seven
electronic databases and a manual search of literature. Only observational
studies with a follow-up period of at least 2 years were included. RESULTS: The
search identified 4081 unique potentially relevant articles, of which 14 met our
inclusion criteria. The presence of family history of psychosis was associated
with poor occupational and global outcome (n=3; r=0.17; P=0.008, n=11; r=0.13;
P=0.002, respectively). CONCLUSION: This was the first systematic review on the
effects of family history of psychosis on occupational and social outcome in
schizophrenia. Based on the review, the presence of family history of psychosis
has a relatively small but statistically significant association with long-term
occupational and global outcome in patients with schizophrenia.
PMID- 25130719
TI - How French paediatric emergency departments manage painful vaso-occlusive
episodes in sickle cell disease patients.
AB - AIM: The most common manifestation of sickle cell disease (SCD) is painful vaso
occlusive episodes (PVOE), and inappropriate treatment leads to unnecessary
suffering and potentially fatal complications. This study describes how French
paediatric emergency departments (EDs) manage PVOE and their knowledge, and
implementation of the French National Authority for Health recommendations on the
management of sickle cell patients. METHODS: A questionnaire on managing PVOE was
sent to all the 111 French paediatric EDs. RESULTS: We received responses from 81
(72.9%) of the EDs. Of those who responded to each individual question, 85% said
that they had read the national recommendations, 71.6% said they used nalbuphine
for moderate PVOE, and 85% used intravenous morphine for severe PVOE. The
majority (91.7%) of EDs thought that intravenous morphine provided relief for
severe PVOE, but only 30.9% thought that intravenous nalbuphine did. A 50:50
nitrous oxide/oxygen mix was used by 71.3% of departments to relieve procedural
pain and by 48% to enhance analgesia when morphine was insufficient for severe
pain. CONCLUSIONS: Most French EDs follow the national recommendations for PVOE.
Nalbuphine was the most commonly used opioid for moderate PVOE and morphine for
severe PVOE. A nitrous oxide/oxygen mixture was widely used for PVOE.
PMID- 25130720
TI - Canalicular network morphology is the major determinant of the spatial
distribution of mass density in human bone tissue: evidence by means of
synchrotron radiation phase-contrast nano-CT.
AB - In bone remodeling, maturation of the newly formed osteonal tissue is associated
with a rapid primary increase followed by a slower secondary increase of
mineralization. This requires supply and precipitation of mineral into the bone
matrix. Mineral delivery can occur only from the extracellular fluid via
interfaces such as the Haversian system and the osteocyte pore network. We
hypothesized that in mineralization, mineral exchange is achieved by the
diffusion of mineral from the lacunar-canalicular network (LCN) to the bone
matrix, resulting in a gradual change in tissue mineralization with respect to
the distance from the pore-matrix interface. We expected to observe alterations
in the mass density distribution with tissue age. We further hypothesized that
mineral exchange occurs not only at the lacunar but also at the canalicular
boundaries. The aim of this study was, therefore, to investigate the spatial
distribution of mass density in the perilacunar and pericanalicular bone matrix
and to explore how these densities are influenced by tissue aging. This is
achieved by analyzing human jawbone specimens originating from four healthy
donors and four treated with high-dosage bisphosphonate using synchrotron
radiation phase-contrast nano-CT with a 50-nm voxel size. Our results provide the
first experimental evidence that mass density in the direct vicinity of both
lacunae (p < 0.001) and canaliculi (p < 0.001) is different from the mean matrix
mass density, resulting in gradients with respect to the distance from both pore
matrix interfaces, which diminish with increasing tissue age. Though limited by
the sample size, these findings support our hypotheses. Moreover, the density
gradients are more pronounced around the lacunae than around the canaliculi,
which are explained by geometrical considerations in the LCN morphology. In
addition, we speculate that mineral exchange occurs at all interfaces of the LCN,
not only in mineralization but also in mineral homeostasis.
PMID- 25130721
TI - RhoA/ROCK pathway mediates p38 MAPK activation and morphological changes
downstream of P2Y12/13 receptors in spinal microglia in neuropathic pain.
AB - Recent studies have indicated an important role of ATP receptors in spinal
microglia, such as P2Y12 or P2Y13, in the development of chronic pain. However,
intracellular signaling cascade of these receptors have not been clearly
elucidated. We found that intrathecal injection of 2-(methylthio)adenosine 5'
diphosphate (2Me-SADP) induced mechanical hypersensitivity and p38 mitogen
activated protein kinase (MAPK) phosphorylation in the spinal cord. Intrathecal
administration of P2Y12/P2Y13 antagonists and Rho-associated coiled-coil
containing protein kinase (ROCK) inhibitor H1152 suppressed not only p38 MAPK
phosphorylation, but also mechanical hypersensitivity induced by 2Me-SADP. In the
rat peripheral nerve injury model, intrathecal administration of antagonists for
the P2Y12/P2Y13 receptor suppressed activation of p38 MAPK in the spinal cord. In
addition, subarachnoidal injection of H1152 also attenuated nerve injury-induced
spinal p38 MAPK phosphorylation and neuropathic pain behavior, suggesting an
essential role of ROCK in nerve injury-induced p38 MAPK activation. We also found
that the antagonists of the P2Y12/P2Y13 receptor and H1152 had inhibitory effects
on the morphological changes of microglia such as retraction of processes in both
2Me-SADP and nerve injured rats. In contrast these treatments had no effect on
the number of Iba1-positive cells in the nerve injury model. Collectively, our
results have demonstrated roles of ROCK in the spinal microglia that is involved
in p38 MAPK activation and the morphological changes. Inhibition of ROCK
signaling may offer a novel target for the development of a neuropathic pain
treatment.
PMID- 25130722
TI - Transcriptional regulation of CCL20 expression.
AB - Chemokines are key mediators of leukocyte recruitment during immunoregulatory and
proinflammatory responses. CCL20 is a cysteine-cysteine chemokine that was
originally shown to be chemotactic for immature dendritic cells, effector or
memory CD4(+) T lymphocytes, and B lymphocytes. Additionally, CCL20 and its only
receptor (CCR6) are exploited by cancer cells for migration and metastatic spread
and play important roles in the development and progression of cancer. However,
it still remains unclear how the activity of the CCL20/CCR6 axis is controlled
and regulated at the transcriptional level. The CCL20 promoter region contains a
transcription start site, a nuclear factor (NF)-kappaB binding site, a
CCAAT/enhancer-binding proteins binding site, an activator protein-1 binding
sites, and a specificity protein 1 (Sp1)-binding site. In this review, we outline
recent advances in our understanding of the structure of the CCL20 promoter
region and discuss the transcriptional regulation of the CCL20 promoter.
PMID- 25130723
TI - Genetic battle between Helicobacter pylori and humans. The mechanism underlying
homologous recombination in bacteria, which can infect human cells.
AB - Helicobacter pylori is a gram-negative pathogenic bacterium that colonises the
human stomach. The chronic infection it causes results in peptic ulcers and
gastric cancers. H. pylori can easily establish a chronic infection even if the
immune system attacks this pathogen with oxidative stress agents and
immunoglobulins. This is attributed to bacterial defence mechanisms against these
stresses. As a defence mechanism against oxidative stresses, in bacterial
genomes, homologous recombination can act as a repair pathway of DNA's double
strand breaks (DSBs). Moreover, homologous recombination is also involved in the
antigenic variation in H. pylori. Gene conversion alters genomic structures of
babA and babB (encoding outer membrane proteins), resulting in escape from
immunoglobulin attacks. Thus, homologous recombination in bacteria plays an
important role in the maintenance of a chronic infection. In addition, H. pylori
infection causes DSBs in human cells. Homologous recombination is also involved
in the repair of DSBs in human cells. In this review, we describe the roles of
homologous recombination with an emphasis on the maintenance of a chronic
infection.
PMID- 25130724
TI - Giving blood donors something to drink before donation can prevent fainting
symptoms: is there a physiological or psychological reason?
AB - The vasovagal reaction has been widely studied but its anatomic and physiological
nature remains uncertain. The mechanisms underlying vasovagal reaction related to
blood donation are not completely understood either. Does its occurrence depend
on the blood donors' physical characteristics and health variables or
psychological factors? On the basis that a psychological approach considerably
prevents donor reactions, the effect of fruit juice ingestion was studied in a
group of 1849 first-time high-school students as a simple strategy to avoid
systemic reactions at blood donation. The reasons for the psychological effect of
this hydration protocol are stressed also in light of previous physiological
studies on the hemodynamic effects of water or carbohydrate drinks.
PMID- 25130725
TI - Comparison of plasma exchange performances between Spectra Optia and COBE Spectra
apheresis systems in repeated procedures considering variability and using
specific statistical models.
AB - Repeated therapeutic plasma exchange (TPE) procedures using centrifugation
techniques became a standard therapy in some diseases. As the new device Spectra
Optia (SPO; Terumo BCT) was available, we studied its performances in repeated
procedures in 20 patients in three apheresis units. First we analysed the
performance results obtained by SPO. Second we compared the performances of the
SPO device to a standard device, COBE Spectra (CSP; Terumo BCT) in the same
patients using statistical method of mixed effects linear regression that
considers variability between patients, centres and apheresis procedures. The
performances analysed were classified according to plasma removal performances
and their consequences on patients whose blood disturbances were assessed.
Primary outcome was plasma removal efficiency (PRE) and PRE-anticoagulant
corrected which was a more accurate parameter. Secondary outcomes corresponded to
the volume of ACD-A consumed, platelets content in waste bag, procedure duration
and status of coagulation system observed after TPE sessions. Before comparing
the performances of both devices we compared the plasma volumes (PVs) processed
in both techniques which showed that the PVs processed in SPO procedures were
lower than in CSP procedures. In these conditions the statistical analysis
revealed similar performances in both apheresis devices in PRE (p = ns) but
better performances with SPO when considering higher PRE corrected by
anticoagulant volume used (p < 0.05). Comparison of secondary outcomes showed no
difference after SPO and CSP. After verifying that pre-apheresis patients'
coagulation blood levels were identical before SPO and CSP, we showed identical
haemostasis disturbances after SPO and CSP but lower platelet losses and higher
fibrinogen post-apheresis blood levels after SPO (p < 0.05). No side effects or
technical complications occurred during and after SPO and CSP. This study
demonstrated that the Spectra Optia device is an alternative device to today's
standard, the COBE Spectra device.
PMID- 25130726
TI - Absolute immature platelet count helps differentiate thrombotic thrombocytopenic
purpura from hypertension-induced thrombotic microangiopathy.
AB - ADAMTS13 activity measurement is used in the diagnostic algorithm of thrombotic
thrombocytopenic purpura (TTP), but results may not be available before
initiation of therapeutic plasma exchange (TPE). The immature platelet fraction
(%-IPF) and the calculated absolute immature platelet count (A-IPC) represent a
test of real-time thrombopoiesis, and can be performed in most laboratories using
automated analyzers. Here we report on using A-IPC kinetics to exclude idiopathic
TTP in a patient with severe hypertension, thrombocytopenia, and acute renal
failure, which was confirmed by a normal ADAMTS13. The complete resolution of
thrombocytopenia occurred once blood pressure was controlled favoring a diagnosis
of hypertension-induced thrombotic microangiopathy.
PMID- 25130727
TI - The effects of anakinra on focal cerebral ischemic injury in rats.
PMID- 25130728
TI - Enzymes for ecdysteroid biosynthesis: their biological functions in insects and
beyond.
AB - Steroid hormones are responsible for the coordinated regulation of many aspects
of biological processes in multicellular organisms. Since the last century, many
studies have identified and characterized steroidogenic enzymes in vertebrates,
including mammals. However, much less is known about invertebrate steroidogenic
enzymes. In the last 15 years, a number of steroidogenic enzymes and their
functions have been characterized in ecdysozoan animals, especially in the fruit
fly Drosophila melanogaster. In this review, we summarize the latest knowledge of
enzymes crucial for synthesizing ecdysteroids, the principal insect steroid
hormones. We also discuss the functional conservation and diversity of
ecdysteroidogenic enzymes in other insects and even non-insect species, such as
nematodes, vertebrates, and lower eukaryotes.
PMID- 25130729
TI - Conformation-specific antibodies to target amyloid beta oligomers and their
application to immunotherapy for Alzheimer's disease.
AB - Amyloid beta-protein (Abeta) oligomers, intermediates of Abeta aggregation, cause
cognitive impairment and synaptotoxicity in the pathogenesis of Alzheimer's
disease (AD). Immunotherapy using anti-Abeta antibody is one of the most
promising approaches for AD treatment. However, most clinical trials using
conventional sequence-specific antibodies have proceeded with difficulty. This is
probably due to the unintended removal of the non-pathological monomer and
fibrils of Abeta as well as the pathological oligomers by these antibodies that
recognize Abeta sequence, which is not involved in synaptotoxicity. Several
efforts have been made recently to develop conformation-specific antibodies that
target the tertiary structure of Abeta oligomers. Here, we review the recent
findings of Abeta oligomers and anti-Abeta antibodies including our own, and
discuss their potential as therapeutic and diagnostic tools.
PMID- 25130730
TI - Simultaneous measurement of nicotinamide and its catabolites, nicotinamide N
oxide, N(1)-methyl-2-pyridone-5-carboxamide, and N(1)-methyl-4-pyridone-3
carboxamide, in mice urine.
AB - Nicotinamide N-oxide is a major nicotinamide catabolite in mice but not in humans
and rats. A high-performance liquid chromatographic method for the simultaneous
measurement of nicotinamide, nicotinamide N-oxide, N(1)-methyl-2-pyridone-5
carboxamide, and N(1)-methyl-4-pyridone-3-carboxamide in mice urine was developed
by modifying the mobile phase of a reported method for measurement of
nicotinamide N-oxide.
PMID- 25130731
TI - cDNA cloning and characterization of vanadium-dependent bromoperoxidases from the
red alga Laurencia nipponica.
AB - The marine red alga genus Laurencia is one of the richest producers of unique
brominated compounds in the marine environment. The cDNAs for two Laurencia
nipponica vanadium-dependent bromoperoxidases (LnVBPO1 and LnVBPO2) were cloned
and expressed in Escherichia coli. Enzyme assays of recombinant LnVBPO1 and
LnVBPO2 using monochlorodimedone revealed that they were thermolabile but their
Km values for Br(-) were significantly lower than other red algal VBPOs. The
bromination reaction was also assessed using laurediol, the predicted natural
precursor of the brominated ether laurencin. Laurediol, protected by
trimethylsilyl at the enyne, was converted to deacetyllaurencin by the LnVBPOs,
which was confirmed by tandem mass spectrometry. Native LnVBPO partially purified
from algal bodies was active, suggesting that LnVBPO is functional in vivo. These
results contributed to our knowledge of the biosynthesis of Laurencia brominated
metabolites.
PMID- 25130732
TI - (2-Nitroethyl)benzene: a major flower scent from the Japanese loquat Eriobotrya
japonica [Rosales: Rosaceae].
AB - (2-Nitroethyl)benzene was identified as a major component of the flower scent of
the Japanese loquat Eriobotrya japonica [Rosales: Rosaceae], together with p
methoxybenzaldehyde and methyl p-methoxybenzoate. The corresponding volatiles
from chopped leaves did not contain these three compounds. This is the first time
that 1-nitro-2-phenyl-ethane has been demonstrated to be a natural product among
Japanese plants, although two Japanese millipedes are known to possess the same
aromatics.
PMID- 25130733
TI - Total synthesis of aurachins C, D, and L, and a structurally simplified analog of
aurachin C.
AB - The quinoline antibiotics aurachins C, D, and L, and a structurally simplified
analog of aurachin C were synthesized from 1-(2-nitrophenyl)butane-1,3-dione via
reductive cyclizations of delta-nitro ketone intermediates, with zinc or iron as
key steps. The results of antimicrobial tests indicate that the N
hydroxyquinolone nucleus mimics the electron carrier in the respiratory chain
more strongly than the quinoline N-oxide nucleus.
PMID- 25130734
TI - Diversity in mRNA expression of the serine-type carboxypeptidase ocpG in
Aspergillus oryzae through intron retention.
AB - Alternative splicing is thought to be a means for diversification of products by
mRNA modification. Although some intron retentions are predicted by transcriptome
analysis in Aspergillus oryzae, its physiological significance remains unknown.
We found that intron retention occurred occasionally in the serine-type
carboxypeptidase gene, ocpG. Analysis under various culture conditions revealed
that extracellular nitrogen conditions influence splicing patterns; this
suggested that there might be a correlation between splicing efficiency and the
necessity of OcpG activity for obtaining a nitrogen source. Since further
analysis showed that splicing occurred independently in each intron, we
constructed ocpG intron-exchanging strain by interchanging the positions of
intron-1 and intron-2. The splicing pattern indicated the probability that ocpG
intron retention was affected by the secondary structures of intronic mRNA.
PMID- 25130736
TI - A genomic search approach to identify carbonyl reductases in Gluconobacter
oxydans for enantioselective reduction of ketones.
AB - The versatile carbonyl reductases from Gluconobacter oxydans in the
enantioselective reduction of ketones to the corresponding alcohols were
exploited by genome search approach. All purified enzymes showed activities
toward the tested ketoesters with different activities. In the reduction of 4
phenyl-2-butanone with in situ NAD(P)H regeneration system, (S)-alcohol was
obtained with an e.e. of up to 100% catalyzed by Gox0644. Under the same
experimental condition, all enzymes catalyzed ethyl 4-chloroacetoacetate to give
chiral products with an excellent e.e. of up to 99%, except Gox0644. Gox2036 had
a strict requirement for NADH as the cofactor and showed excellent
enantiospecificity in the synthesis of ethyl (R)-4-chloro-3-hydroxybutanoate. For
the reduction of ethyl 2-oxo-4-phenylbutyrate, excellent e.e. (>99%) and high
conversion (93.1%) were obtained by Gox0525, whereas the other enzymes showed
relatively lower e.e. and conversions. Among them, Gox2036 and Gox0525 showed
potentials in the synthesis of chiral alcohols as useful biocatalysts.
PMID- 25130735
TI - A genome-wide survey of homeodomain-leucine zipper genes and analysis of cold
responsive HD-Zip I members' expression in tomato.
AB - Homeodomain-leucine zipper (HD-Zip) proteins are a kind of transcriptional
factors that play a vital role in plant growth and development. However, no
detailed information of HD-Zip family in tomato has been reported till now. In
this study, 51 HD-Zip genes (SlHZ01-51) in this family were identified and
categorized into 4 classes by exon-intron and protein structure in tomato
(Solanum lycopersicum) genome. The synthetical phylogenetic tree of tomato,
Arabidopsis and rice HD-Zip genes were established for an insight into their
evolutionary relationships and putative functions. The results showed that the
contribution of segmental duplication was larger than that of tandem duplication
for expansion and evolution of genes in this family of tomato. The expression
profile results under abiotic stress suggested that all SlHZ I genes were
responsive to cold stress. This study will provide a clue for the further
investigation of functional identification and the role of tomato HD-Zip I
subfamily in plant cold stress responses and developmental events.
PMID- 25130737
TI - IkappaB kinase epsilon expression in adipocytes is upregulated by interaction
with macrophages.
AB - Macrophage infiltration in the adipose tissue, and the interaction with
adipocytes, is well documented to be involved in fat inflammation and obesity
associated complications. In this study, we isolated IkappaB kinase epsilon
(IKKepsilon) as a key adipocyte factor that is potentially affected by
interaction with macrophages in adipose tissue in vivo. We showed that IKKepsilon
mRNA expression levels in white adipose tissue were increased in both genetic and
diet-induced obese mouse. Furthermore, IKKepsilon mRNA expression was decreased
by the administration of vitamin B6, an anti-inflammatory vitamin, and that
IKKepsilon expression levels in adipose tissue were closely correlated with the
numbers of infiltrating macrophages. In a co-culture system, we showed that
IKKepsilon expression in adipocytes was upregulated by interaction with activated
macrophages. This study provides novel insight into IKKepsilon, which is involved
in adipose tissue inflammation during the development of obesity.
PMID- 25130738
TI - Down-regulated miR-15a mediates the epithelial-mesenchymal transition in renal
tubular epithelial cells promoted by high glucose.
AB - High glucose (HG) has been reported to be associated with renal dysfunction. And
one potential mechanism underlining the dysfunction is the epithelial-mesenchymal
transition (EMT) of renal tubular epithelial cells. Present study showed that EMT
was induced in the HG-treated renal tubular epithelial cells by promoting the
expression of mesenchymal phenotype molecules, such as alpha-SMA and collagen I,
and down-regulating the expression of epithelial phenotype molecule E-cadherin.
Moreover, we have identified the down-regulation of miR-15a which was accompanied
with the HG-induced EMT. And the miR-15a overexpression inhibited the alpha-SMA,
collagen I expression, and the promotion of E-cadherin expression by targeting
and down-regulating AP4 which was also significantly promoted by the HG in the
renal tubular epithelial cells. Thus, this study revealed that the weakening
regulation on the AP4 expression by miR-15a might contribute to the HG-induced
EMT in the renal tubular epithelial cells.
PMID- 25130740
TI - Glutathione contributes to the efflux of selenium from hepatoma cells.
AB - Selenite is a selenium source for selenoprotein biosynthesis in mammalian cells.
Although previous studies have suggested the involvement of glutathione (GSH)
and/or thioredoxin reductase in selenite metabolism, intracellular selenite
metabolism remains largely unknown. Here, we report that GSH depletion did not
affect the amount of selenoprotein in Hepa 1-6 cells, suggesting that GSH does
not play a central role in the reduction of selenite in selenoprotein
biosynthesis. On the other hand, we found that GSH is involved in the efflux of
low-molecular-weight selenium compounds from cells, presumably via the formation
of selenodiglutathione. Moreover, selenite inhibited the efflux of a fluorescent
bimane-GS conjugate that is mediated by ATP-dependent multidrug-resistant
proteins, implying the existence of an active transporter for
selenodiglutathione. This is the first report demonstrating that GSH plays a role
in selenium excretion from cells by forming a GSH-conjugate, which may contribute
to the distribution, detoxification, and homeostasis of selenium in the body.
PMID- 25130741
TI - Regio- and stereoselective oxygenation of proline derivatives by using microbial
2-oxoglutarate-dependent dioxygenases.
AB - We evaluated the substrate specificities of four proline cis-selective
hydroxylases toward the efficient synthesis of proline derivatives. In an initial
evaluation, 15 proline-related compounds were investigated as substrates. In
addition to l-proline and l-pipecolinic acid, we found that 3,4-dehydro-l
proline, l-azetidine-2-carboxylic acid, cis-3-hydroxy-l-proline, and l
thioproline were also oxygenated. Subsequently, the product structures were
determined, revealing cis-3,4-epoxy-l-proline, cis-3-hydroxy-l-azetidine-2
carboxylic acid, and 2,3-cis-3,4-cis-3,4-dihydroxy-l-proline.
PMID- 25130739
TI - Bisphenol A exerts estrogenic effects by modulating CDK1/2 and p38 MAP kinase
activity.
AB - Bisphenol A (BPA) is considered to be an endocrine disruptor, but the mechanisms
by which it disrupts endocrine functions are poorly understood. Here, we have
shown that BPA binds both estrogen receptor (ER)-alpha and ER-beta (ER-beta)
using a fluorescence polarization competitive binding assay. In addition, we
found that BPA induced cell proliferation by modulating cell cycle-related genes
in the MCF-7 human mammary cancer cell line. Moreover, using a BG1 luciferase ER
transactivation assay, we found that BPA has estrogenic activity. Modulating the
MAPK pathway by using an ERK inhibitor (PD98059) or a JNK inhibitor (SP600125)
had no effect on the ability of BPA to induce estrogenic activity. However, the
antiestrogen, ICI 182,780, and the p38 inhibitor, PD 169316 successfully blocked
BPA-induced estrogenic activity. Our findings suggest that BPA mimics ER
dependent estrogenic activity by targeting proteins that regulate the cell cycle
and p38 MAPK.
PMID- 25130742
TI - Ethanol stress impairs protein folding in the endoplasmic reticulum and activates
Ire1 in Saccharomyces cerevisiae.
AB - Impaired protein folding in the endoplasmic reticulum (ER) evokes the unfolded
protein response (UPR), which is triggered in budding yeast, Saccharomyces
cerevisiae, by the ER-located transmembrane protein Ire1. Here, we report that
ethanol stress damages protein folding in the ER, causing activation of Ire1 in
yeast cells. The UPR likely contributes to the ethanol tolerance of yeast cells.
PMID- 25130743
TI - Anti-diabetic properties of Daphniphyllum macropodum fruit and its active
compound.
AB - We evaluated in vitro anti-diabetic activities of 497 native plants of Jeju
Island (South Korea) by measuring the induction of adipocyte differentiation.
Among the plants, Daphniphyllum macropodum fruit extract (DME) had the highest
peroxisome proliferator-activated receptor gamma (PPARgamma) agonist activity and
was therefore selected as a potential source of anti-diabetic agents. To
elucidate the active components of DME, constituent compounds were purified and
their effects on the adipocyte differentiation were studied. Using activity
guided fractionation, four compounds were isolated from DME and their adipogenic
effects were evaluated. Among the compounds isolated, 5,7-dihydroxychromone
potently induced the differentiation of mouse 3T3-L1 preadipocytes. DME and 5,7
dihydroxychromone increased PPARgamma and liver X receptor alpha (LXRalpha) mRNA
expression levels. To determine whether the adipogenic effects we observed might
affect serum glucose levels, we undertook in vivo experiment using streptozotocin
/high-fat diet-induced type 2 diabetes mouse model. DME supplementation reduced
serum glucose, total cholesterol, and triacylglycerol levels in diabetes mice.
These results suggest that DME may be useful for the prevention and treatment of
type 2 diabetes mellitus. Moreover, it was proposed that 5,7-dihydroxychromone
isolated from DME is one of the active compounds that may contribute to regulate
blood glucose levels.
PMID- 25130744
TI - Unripe Rubus coreanus Miquel suppresses migration and invasion of human prostate
cancer cells by reducing matrix metalloproteinase expression.
AB - Rubus coreanus Miquel (RCM) is used to promote prostate health and has been shown
to have anti-oxidant and anti-carcinogenic activities. However, the effects and
mechanisms of RCM on prostate cancer metastasis remain unclear. PC-3 and DU 145
cells were treated with ethanol or water extract of unripe or ripe RCM and
examined for cell invasion, migration, and matrix metalloproteinases (MMPs)
activity and expression. Phosphoinositide 3-kinase (PI3K) and Akt activities were
examined. Unripe RCM extracts exerted significant inhibitory effects on cell
migration, invasion, and MMPs activities. A significant reduction in MMPs
activities by unripe RCM ethanol extract treatment (UE) was associated with
reduction of MMPs expression and induction of tissue inhibitors of
metalloproteinases (TIMPs) expression. Furthermore, PI3K/Akt activity was
diminished by UE treatment. In this study, we demonstrated that UE decreased
metastatic potential of prostate cancer cells by reducing MMPs expression through
the suppression of PI3K/Akt phosphorylation, thereby decreasing MMP activity and
enhancing TIMPs expression.
PMID- 25130745
TI - Effects of drying conditions on moisture distribution in rehydrated spaghetti.
AB - Moisture distributions in spaghettis prepared at a maximum temperature of 50, 70,
or 85 degrees C, designated as LT-, HT-, or VHT-spaghetti, respectively, and
cooked to the average moisture content of 1.71 +/- 0.01 kg-H2O/kg-d.m., were
measured. The moisture contents near the surface and at the center of the LT
spaghetti were lower and higher, respectively, than those of HT- and VHT
spaghetti.
PMID- 25130747
TI - Diallyl trisulfide induces apoptosis in Jurkat cells by the modification of
cysteine residues in thioredoxin.
AB - We reported the regulation of protein function by oxidative modification of the
specific cysteine residue(s) by diallyl trisulfide (DATS). In this study, we
examined if DATS modifies the cysteine residue of thioredoxin (Trx) by urea
polyacryl amide gel electrophoresis. DATS modified two specific cysteine residues
in Trx and this oxidative modification of cysteine residues would be sole
causative of the apoptosis induced by DATS in leukemic cells.
PMID- 25130748
TI - Optimization of culture conditions of Fusarium solani for the production of neoN
methylsansalvamide.
AB - The aim of this study was to optimize the culture conditions of Fusarium solani
KCCM90040 on cereal grain for the production of neoN-methylsansalvamide, a novel
low-molecular-weight cyclic pentadepsipeptide exhibiting cytotoxic and multidrug
resistance reversal effects. From the analysis of variance results using response
surface methodology, temperature, initial moisture content, and growth time were
shown to be important parameters for the production of neoN-methylsansalvamide on
cereal grain. A model was established in the present study to describe the
relationship between environmental conditions and the production of neoN
methylsansalvamide on rice, the selected cereal grain. The optimal culture
conditions were determined at 25.79 degrees C with the initial moisture content
of 40.79%, and 16.19 days of growth time. This report will give important
information concerning the optimization of environmental conditions using
statistic methodology for the production of a new cyclic pentadepsipeptide from
fungi.
PMID- 25130746
TI - Identification of molecular target of diallyl trisulfide in leukemic cells.
AB - To identify the molecular target of diallyl trisulfide (DATS) in human leukemic
cell line U937, we examined modification of thiol group(s) of cellular proteins
by the redox 2D PAGE. A unique protein spot appeared by DATS treatment was
identified to be heat shock protein 27 (HSP27). Hsp27 is suggested to be one of
the molecular target of DATS in U937.
PMID- 25130749
TI - A cell wall protein (YqgA) is genetically related to the cell wall-degrading dl
endopeptidases in Bacillus subtilis.
AB - The Gram-positive bacterium Bacillus subtilis has a thick cell wall. The cell
wall contains various proteins, both for secretion and for peptidoglycan (PG)
maintenance. Penicillin-binding proteins for PG synthesis, PG hydrolases
(autolysins), and regulator proteins for the autolysins are the known components
of the PG maintenance system. YqgA was identified as an abundant protein attached
to the cell wall of B. subtilis through a proteomics analysis. The YqgA protein
was localized at cell division sites during the transition period between the
exponential and the stationary phases. YqgA localization was affected by
mutations in the dl-endopeptidases (DLEPases), which are the autolysins involved
in cell morphogenesis. Furthermore, yqgA mutations on a background of defective
DLEPases led to delays in cell growth and cell morphological changes. These
results demonstrate that yqgA is genetically related to the genes encoding
DLEPases involved in cell morphogenesis.
PMID- 25130750
TI - Comparison of hydrophilic variation and bioethanol production of furfural
residues after delignification pretreatment.
AB - Furfural residue (FR) is a waste lignocellulosic material with enormous potential
for bioethanol production. In this study, bioethanol production from FR after
delignification was compared. Hydrophilic variation was measured by
conductometric titration to detect the relationship between hydrophilicity and
bioethanol production. It was found that ethanol yield increased as
delignification enhanced, and it reached up to 75.6% of theoretical yield for
samples with 8.7% lignin. The amount of by-products decreased as delignification
increased. New inflection points appeared in conductometric titration curves of
samples that were partially delignified, but they vanished in the curves of the
highly delignified samples. Total charges and carboxyl levels increased after
slight delignification, and they decreased upon further delignification. These
phenomena suggested some new hydrophilic groups were formed during pretreated
delignification, which would be beneficial to enzymatic hydrolysis. However, some
newly formed groups may act as toxicant to the yeast during simultaneous
saccharification and fermentation.
PMID- 25130751
TI - Evaluation of bifidobacterial adhesion to acidic sugar chains of porcine colonic
mucins.
AB - The aim of this study was to assess the adhesion of Bifidobacterium strains to
acidic carbohydrate moieties of porcine colonic mucin. Mucins were extracted and
purified via gel filtration chromatography followed by density-gradient
ultracentrifugation. The presence of sulfated and sialylated carbohydrates in
mucins was shown by enzyme-linked immunosorbent assays using PGM34 and HMC31
monoclonal antibodies (mAbs), respectively. Adhesion of Bifidobacterium strains
to mucin preparations was markedly affected by the degree of purification. In
eight of 22 strains, we observed increased adhesion to mucin preparations
purified by ultracentrifugation. Moreover, in some of these eight strains,
adhesion to mucin was reduced by pretreatment with sulfatase and/or sialidase,
and competitively inhibited by pretreatment with PGM34 and/or HCM31 mAbs. Our
results showed that some Bifidobacterium strains adhered to sulfo- and/or
sialomucin and were able to recognize carbohydrate structures of the mAbs
epitopes.
PMID- 25130752
TI - Antioxidant activities of cysteine derivatives against lipid oxidation in
anhydrous media.
AB - This study investigated antioxidant activities of cysteine derivatives of amino
and carboxylic acid moieties against lipid oxidation in anhydrous acetonitrile.
Only cysteine derivatives bearing free amino or carboxylate ion were found to
exert potent antioxidant activities. Sequential proton loss and electron transfer
like proton shift and subsequent electron transfer (PS-ET) mechanism may
facilitate the antioxidant activities of cysteine derivatives against lipid
oxidation in anhydrous media.
PMID- 25130753
TI - Pattern of visuospatial lateralization in two corvid species, black-billed
magpies and Clark's nutcrackers.
AB - Cerebral lateralization is widespread amongst vertebrate species suggesting
advantages are gained by having one of the brain's hemispheres exert dominant
control over certain cognitive functions. A recently devised task for assessing
lateralization of visuospatial attention by birds (Diekamp et al., 2005) has
allowed researchers to suggest the corpus callosum may not be necessary for the
emergence of such asymmetries. More recently, this task has been adopted to
examine the embryonic development of lateralization in birds, research which may
provide important insights as to the underlying genetic mechanisms (Chiandetti,
2011; Chiandetti et al., 2013) of vertebrate cerebral lateralization. However, to
date only chicks and pigeons have been used in this paradigm. Thus, it is unclear
whether other avian species will also show lateralization of visuospatial
attention during this task. Here, we examined the pattern of visuospatial
lateralization in two corvid species: social black-billed magpies (Pica hudsonia)
and non-social Clark's nutcrackers (Nucifraga columbiana). We find that neither
the magpies nor the nutcrackers show evidence for population level lateralization
or predictable individual level lateralization, as only a subset of individuals
of each species showed a significant individual bias, which were rarely stable
over repeated testing.
PMID- 25130754
TI - Influence of temperament score and handling facility on stress, reproductive
hormone concentrations, and fixed time AI pregnancy rates in beef heifers.
AB - The objectives were (i) to evaluate the effect of temperament, determined by
modified 2-point chute exit and gait score, on artificial insemination (AI)
pregnancy rates in beef heifers following fixed time AI and (ii) to determine the
effect of temperament on cortisol, substance-P, prolactin and progesterone at
initiation of synchronization and at the time of AI. Angus beef heifers (n = 967)
at eight locations were included in this study. At the initiation of
synchronization (Day 0 = initiation of synchronization), all heifers received a
body condition score (BCS), and temperament score (0 = calm; slow exit and walk
or 1 = excitable; fast exit or jump or trot or run). Blood samples were collected
from a sub-population of heifers (n = 86) at both synchronization initiation and
the time of AI to determine the differences in serum progesterone, cortisol,
prolactin and substance-P concentrations between temperament groups. Heifers were
synchronized with 5-day CO-Synch+ controlled internal drug release (CIDR)
protocol and were inseminated at 56 h after CIDR removal. Heifers were examined
for pregnancy by ultrasound 70 days after AI to determine AI pregnancy.
Controlling for synchronization treatment (p = 0.03), facility design (p = 0.05),
and cattle handling facility design by temperament score interaction (p = 0.02),
the AI pregnancy differed between heifers with excitable and calm temperament
(51.9% vs 60.3%; p = 0.01). The alley-way with acute bends and turns, and long
straight alley-way had lower AI pregnancy rate than did the semicircular alley
way (53.5%, 56.3% and 67.0% respectively; p = 0.05). The serum hormone
concentrations differed significantly between different types of cattle handling
facility (p < 0.05). The cattle handling facility design by temperament group
interactions significantly influenced progesterone (p = 0.01), cortisol (p =
0.01), prolactin (p = 0.02) and substance-P (p = 0.04) both at the initiation of
synchronization and at the time of AI. Inter- and intra-rater agreement for
temperament scoring were moderate and good (Kappa = 0.596 +/- 0.07 and 0.797 +/-
0.11) respectively. The predictive value for calm and pregnant to AI was 0.87,
and excited and non-pregnant to AI was 0.76. In conclusion, the modified 2-point
temperament scoring method can be used to identify heifers with excitable
temperament. Heifers with excitable temperament had lower AI pregnancy. Further,
cattle handling facility design influenced the temperament and AI pregnancy.
PMID- 25130755
TI - Cranial nerve VI palsy as an initial presentation of necrotizing sarcoid
granulomatosis in a 14-year-old female: case report and literature review.
AB - OBJECTIVES: We describe a case of pediatric necrotizing sarcoid granulomatosis
(NSG) presenting with right cranial nerve VI palsy and multiple lung nodules,
successfully treated with corticosteroids. METHODS: This is a descriptive case
report of one patient with review of the literature. RESULTS: A 14-year-old
Caucasian female presented with complaints of pain on inspiration and dyspnea on
exertion, as well as diplopia that was worse with right gaze. The patient
presented to our emergency department with persistent diplopia and was found to
have stable right cranial nerve VI palsy. CTA showed multiple pulmonary nodules.
Despite continued extensive multispecialty work-up, the patient's cranial nerve
VI palsy had not resolved, thus tissue confirmation via lung biopsy was
performed. Pathologic diagnosis revealed necrotizing sarcoid granulomatosis. The
patient was subsequently started on intravenous corticosteroids, which led to the
rapid resolution of her presenting symptoms. CONCLUSIONS: Necrotizing sarcoid
granulomatosis is a multisystem organ disease that is rare in children. Pathology
commonly reveals epithelioid noncaseating granuloma and granulomatous vasculitis
with necrosis. We report an unusual presentation involving sixth nerve palsy in a
14-year-old girl. Diagnosis was determined and confirmed by histopathology of a
pulmonary nodule biopsy. This is the first case to our knowledge of NSG
presenting with cranial nerve palsy in a pediatric patient.
PMID- 25130756
TI - Do hospitalists overuse proton pump inhibitors? Data from a contemporary cohort.
PMID- 25130757
TI - Evidence for multiple paternity in the school shark Galeorhinus galeus found in
New Zealand waters.
AB - This study assessed the levels of relatedness of Galeorhinus galeus of progeny
arrays using six microsatellite DNA markers. A parentage analysis from five
families (mother and litter) from the North Island of New Zealand suggested the
occurrence of genetic polyandry in G. galeus with two of the five litters showing
multiple sires involved in the progeny arrays. This finding may be consistent
with the reproductive characteristics of G. galeus, in which females can
potentially store sperm for long periods of time after the mating season.
PMID- 25130758
TI - Metal deposition at the liquid-liquid interface.
AB - Metal nanoparticles are readily formed, with a reasonable degree of size and
shape control, using solution-based reduction methods under ambient conditions.
Despite the large number of reports in this field, much of our knowledge of
nanoparticle growth is largely empirical, with the relationship between particle
form and growth conditions, for example, still not well understood. Many
nanoparticle preparation routes actually depend on not one, but two, solution
phases, i.e. the syntheses involve reaction or transfer at the liquid-liquid
(organic-water) interface. This interface can be polarised electrochemically, an
approach that offers promise as a route to better understanding, and ultimately
control, of nanoparticle growth.
PMID- 25130759
TI - An Evaluation of Laboratory Efficiency in Shanghai Emergency by Turn Around Times
Level.
AB - OBJECTIVE: China launched a health care reform policy due to the aging population
and rapid urbanization. However, emergency overcrowding is not improved. We
assessed the laboratory efficiency of emergency department (ED) in Shanghai
hospitals. METHODS: We recorded the turn around times for processing laboratory
biomarkers to assess laboratory efficiency at 17 EDs in national/regional
hospitals. We compared TAT between national and regional hospitals and between
central and ED laboratories to analyze the relationship between the laboratory
efficiency and the ED overcrowding. RESULTS: All the participating hospitals have
an emergency laboratory. The median TAT for c-TNT was 61 min (46-76 min) at
regional EDs compared with 64 min (46-87 min) at national EDs; therefore, the TAT
at regional EDs were more efficient (P < 0.05). The TAT were longer (65 min (53
85 min)) at ED labs than (60 min (42-83 min)) at central labs (P < 0.05),
independent of the hospital tier and working period. We discovered that only 9%
of investigated samples at Tier II EDs and 5% at Tier III EDs were assayed by
point-of-care (POC) instruments. CONCLUSION: Our TAT level is approaching the
recommended international standard. However, the TAT evaluation from ED
laboratories demonstrates that their existence does not decrease the waiting time
for laboratory reports compared to central laboratory. Thus, they have not yet
approached a level to share the burden of the ED overcrowding. Further
arrangement should be assigned to separate the function of emergency laboratory
and central laboratory. It is worth deploying the POC assay in the ED, which will
save twice the TAT level. The idea of evaluating routine laboratory efficiency by
TAT at ED is fast, convenient, although it does not represent the general level
of laboratory efficiency.
PMID- 25130760
TI - Sleep duration, sleep quality, and obesity risk among older adults from six
middle-income countries: findings from the study on global AGEing and adult
health (SAGE).
AB - OBJECTIVES: Changes in sleep patterns often occur in older adults. Previous
studies have documented associations between sleep duration, sleep quality, and
obesity risk in older individuals, yet few studies have examined these trends in
lower-income countries. The present cross-sectional study uses nationally
representative datasets from six countries to examine these relationships.
METHODS: Two hypotheses related to obesity risk and sleep patterns were tested
using data from the first wave of the World Health Organization's Study on global
AGEing and adult health (SAGE). This longitudinal study draws on samples of older
adults (>50 years old) in six middle-income countries (China, Ghana, India,
Mexico, Russian Federation, and South Africa). Self-report data were used to
measure sleep duration, sleep quality, lifestyle and sociodemographic
information, while anthropometric measurements were collected to assess body mass
index (BMI) and waist circumference (WC). Multiple linear regressions were used
to examine the relationship between sleep patterns and obesity risk while
controlling for lifestyle factors. RESULTS: Shorter sleep durations in both men
and women were significantly associated with higher BMI and WC measures (P <
0.05). Low sleep quality did not significantly contribute to increased obesity
risk. Surprisingly, high sleep quality was significantly associated with
increased male BMI and WC in China and India (P < 0.01). CONCLUSIONS: This study
documented an association between short sleep duration and increased obesity
risk, which is important given the global increase of obesity-related diseases.
PMID- 25130761
TI - Flexor tendons repair: effect of core sutures caliber with increased number of
suture strands and peripheral sutures. A sheep model.
AB - BACKGROUND: Surgeons have aimed to achieve strong repair so as to begin early
active rehabilitation programs for flexor tendon injury. Multi-strand suture
techniques were developed to gain improved gap resistance and ultimate force
compared with the respective two-strand techniques. In vivo studies indicate that
multiple strands may cause ischemia during the intrinsic healing process by
decreasing the total cross-sectional area of the injured site, unless the total
cross-sectional area of the sutures is not decreased. HYPOTHESIS: The hypothesis
was to design an in vitro study to understand the biomechanical relationship
between suture calibers of core sutures with increased number of suture strands
and peripheral suture on final repair strength. MATERIALS AND METHODS: Sixty
fresh sheep forelimb flexor digitorum profundus tendons were randomly placed into
three groups (A, B, and C), each containing 20 specimens, for tendon repair. Two
, four-, and eight-strand suture techniques were respectively used in Groups A,
B, and C. A simple running peripheral suture technique was used in Subgroups A2,
B2, and C2. For each repaired tendon, the 2-mm gap-formation force, 2-mm gap
formation strength, maximum breaking force and maximum breaking strength were
determined. RESULTS: Differences in 2-mm gap-formation force and 2-mm gap
formation strength were found between Subgroups A1 and A2, B1 and B2, and C1 and
C2. Between Groups A and B, A and C, and B and C, there was no difference as
well. CONCLUSION: Both the number of strands and the ratio between the total
suture volume and tendon volume at the repair site are important for ideal
repair. If the total cross-sectional area of the sutures is equal in 2-strand, 4
strand, and 8-strand procedure, there is no difference in the strength of the
repair. A decrease in caliber size suture requires more passes to achieve the
same strength. Instead, it is much better to use peripheral suture techniques to
improve the strength of the repair with larger diameter 2-strand core sutures.
PMID- 25130762
TI - Stemmed hemiarthroplasty versus resurfacing in primary shoulder osteoarthritis: a
single-center retrospective series of 78 patients.
AB - INTRODUCTION: Resurfacing shoulder arthroplasty is proposed in primary
osteoarthritis of the shoulder. The present study compared resurfacing versus 3rd
generation stemmed hemiarthroplasty in terms of survival, functional results and
implant positioning effects. MATERIALS AND METHODS: Seventy eight patients
underwent arthroplasty for primary osteoarthritis of the shoulder: 41 by
resurfacing and 37 by stemmed hemiarthroplasty. The two populations were
comparable on all baseline variables. Minimum follow-up was 2 years. The
principal assessment criterion was survivorship with surgical revision as end
point. Secondary criteria were functional results on Constant, quick-DASH, Neer
and SSV scores, and implant positioning effects assessed on radiology. RESULTS:
At a mean 44 months' follow-up (range, 24-118 months), there were no significant
differences in functional scores. Radiologic analysis found greater varus
positioning and lateral offset of the humeral head in resurfacing compared with
stemmed hemiarthroplasty (128 degrees vs 138 degrees , P<0.01; 6.5 +/- 2 vs 4.6
+/- 1.6mm, P<0.01). Survivorship without revision was significantly poorer in
resurfacing, with 4 revision procedures for glenoid wear (9.8%), versus none in
hemiarthroplasty (P=0.02). There was no correlation between humeral head size,
positioning or lateral offset and revision. CONCLUSION: Revision-free survival
was significantly lower in resurfacing than in hemiarthroplasty. Greater humeral
head size may increase lateral offset, accelerating glenoid wear. Down-sizing the
humeral head in resurfacing procedures might limit these complications. LEVEL OF
EVIDENCE: Level III; case-control study.
PMID- 25130763
TI - Does Biolox Delta ceramic reduce the rate of component fractures in total hip
replacement?
AB - Biolox Delta ceramic has been optimized with nano-sized, yttria-stabilized
tetragonal zirconium and strontium oxide to help limit cracking propagation.
Although its mechanical properties are better than those of earlier generation
ceramics, existing data on this material are limited, thus the goals of this
study were to determine: 1) the remaining rate of implant fracture; 2) the ideal
combination of head diameter and component position. Hypothesis. We hypothesized
that the use of the ceramic composite Biolox Delta had reduced the risk of
implant fracture. Materials and methods. The bibliographic search (in Pubmed
database with the key words "ceramic fracture" and "total hip prosthesis ")
identified 46 articles on fractures in third or fourth generation ceramic
components, including 5 involving Biolox Delta. Manufacturer's data and ANSM
(Agence nationale de securite du medicament et des produits de sante) (National
Agency for Safety of Drugs and Medical Products) reports were compared with the
few clinical cases published in the literature. Results. According to the
manufacturer (CeramTec GmbH, Plochingen, Germany), the use of Biolox Delta
ceramic has reduced the rate of femoral head fractures to 0.003% compared to
0.021% with alumina ceramic. The fracture rate of liners has remained stable, at
approximately 0.03%. The number of ANSM reports confirmed these tendencies. The
rate of head component fractures decreases as the head diameter increases. The
quality of impaction on the morse taper (cleanliness of the taper, insertion
along the axis) plays an important role. Although it is generally only available
for cup sizes above 50mm, a 36-mm head diameter seems to be optimal because it
prevents impingement between the cup rim and the neck of the stem, without
increasing micro-separation with larger diameters. Conclusion. Although Biolox
Delta ceramic is more resistant to fractures than alumina ceramic, it can be
fractured under suboptimal implantation conditions including edge loading. Its
use requires the same precautions as other hard-on-hard bearings and requires
special attention to cup position, insertion on or in morse tapers and adjustment
of leg length. LEVEL OF EVIDENCE: V expert's opinion.
PMID- 25130764
TI - Estimating premium sensitivity for children's public health insurance coverage:
selection but no death spiral.
AB - OBJECTIVE: To estimate the effect of premium increases on the probability that
near-poor and moderate-income children disenroll from public coverage. DATA
SOURCES: Enrollment, eligibility, and claims data for Georgia's PeachCare for
Kids(TM) (CHIP) program for multiple years. STUDY DESIGN: We exploited policy
induced variation in premiums generated by cross-sectional differences and
changes over time in enrollee age, family size, and income to estimate the
duration of enrollment as a function of the effective (per child) premium. We
classify children as being of low, medium, or high illness severity. PRINCIPAL
FINDINGS: A dollar increase in the per-child premium is associated with a slight
increase in a typical child's monthly probability of exiting coverage from 7.70
to 7.83 percent. Children with low illness severity have a significantly higher
monthly baseline probability of exiting than children with medium or high illness
severity, but the enrollment response to premium increases is similar across all
three groups. CONCLUSIONS: Success in achieving coverage gains through public
programs is tempered by persistent problems in maintaining enrollment, which is
modestly affected by premium increases. Retention is subject to adverse selection
problems, but premium increases do not appear to significantly magnify the
selection problem in this case.
PMID- 25130765
TI - Multidimensional analysis of nanoparticles with highly disperse properties using
multiwavelength analytical ultracentrifugation.
AB - The worldwide trend in nanoparticle technology toward increasing complexity must
be directly linked to more advanced characterization methods of size, shape and
related properties, applicable to many different particle systems in science and
technology. Available techniques for nanoparticle characterization are
predominantly focused on size characterization. However, simultaneous size and
shape characterization is still an unresolved major challenge. We demonstrate
that analytical ultracentrifugation with a multiwavelength detector is a powerful
technique to address multidimensional nanoparticle analysis. Using a high
performance optical setup and data acquisition software, information on size,
shape anisotropy and optical properties were accessible in one single experiment
with unmatched accuracy and resolution. A dynamic rotor speed gradient allowed us
to investigate broad distributions on a short time scale and differentiate
between gold nanorod species including the precise evaluation of aggregate
formation. We report how to distinguish between different species of single-wall
carbon nanotubes in just one experiment using the wavelength-dependent
sedimentation coefficient distribution without the necessity of time-consuming
purification methods. Furthermore, CdTe nanoparticles of different size and
optical properties were investigated in a single experiment providing important
information on structure-property relations. Thus, multidimensional information
on size, density, shape and optical properties of nanoparticulate systems becomes
accessible by means of analytical ultracentrifugation equipped with
multiwavelength detection.
PMID- 25130766
TI - Addressing the shortage of health professionals in South Africa through the
development of a new cadre of health worker: the creation of Clinical Associates.
AB - South Africa made a decision in 2002 to develop so-called mid-level medical
workers, now known as clinical associates. This article describes the background
to this decision, and the national process of developing the profession and its
scope of practice, which was aligned with the needs of the health service,
particularly those of rural district hospitals. A common national curriculum was
then developed, with implementation in three faculties. The first graduates have
entered the profession, starting in 2011, and are in the process of establishing
themselves across the country. They are already making an important contribution
to rural health care, and are seeking ways in which the profession can be
enhanced to ensure sustainability. The profession needs to adapt itself to the
changing realities of the South African context.
PMID- 25130767
TI - Sudden death in a 15-year-old with diffuse cardiac rhabdomyomatosis: an autopsy
case report.
AB - A 15-year-old African-American female with a 4-month history of sporadic rapid
heartbeat and fatigue was found pulseless and apneic in her residence. At
autopsy, patchy scarring was diffuse throughout the circumference of the left
ventricle of the heart. Microscopically, the myocardium had diffuse infiltration
of rhabdomyoma-like cells with significant associated fibrosis. Unlike cardiac
rhabdomyoma, there was no discrete tumor mass. Differential diagnoses considered
were congenital cardiac rhabdomyoma with partial regression, cardiac fibroma,
histiocytoid cardiomyopathy, glycogen storage diseases, and drug-induced vacuolar
cardiomyopathy. However, the findings are most consistent with cardiac
rhabdomyomatosis, an entity not well described in the literature.
PMID- 25130769
TI - Relations between virtues and positive mental health in a Korean population: a
Multiple Indicators Multiple Causes (MIMIC) model approach.
AB - A Multiple Indicators Multiple Causes (MIMIC) approach was applied to investigate
the relationship between virtues and positive mental health as determined using
the Character Strength Test and the Mental Health Continuum-Short Form. The study
participants were 876 college students (54% women; overall mean age [SD] 21.50
years [2.35]) recruited from introductory psychology courses at two universities
in Seoul. Findings revealed that the intellectual virtues of college students
predicted subjective well-being according to all emotional, social and
psychological measures. Results are discussed in the context of previous work
using the Values in Action classification of virtues and character strengths. In
addition, implications regarding understanding the nature and possible origins of
positive mental health are outlined.
PMID- 25130768
TI - Comparative study of temporary effect on the water content at different depths of
the skin by hot and cold moisturizing formulations.
AB - BACKGROUND: Researchers have studied the water content at different skin depths.
Since skin differs among tissue depth, we sought to determine the depth
variability of the water content after moisturizing formulation application.
Furthermore, we compared the effects of formulations with different type of
manufacturing processes (hot and cold process). METHODS: To characterize the
variations in the water content at different depths in the skin, measurements
were done on the center of the inner forearm middle line of 18 sitting healthy
women, before and after 1, 3, and 5 h of the application of two different
moisturizing formulations (hot and cold process). Measurements included stratum
corneum hydration via capacitance (SC) at 1.25 MHz (30-40 MUm), and dermal water
via tissue dielectric constant (TDC) at 300 MHz to depths of 500, 1500, and 2500
MUm. RESULTS: There were significant differences between the SC mean values at
all evaluated time intervals after application of both formulations when compared
to baseline before application (T0). The SC mean values at 1 and 3 h are higher
than those of the 5 h post application for both formulations. When comparing the
formulations, hot formulation shows higher SC levels at 3 and 5 h, than cold
formulation. TDC mean values to skin depths of 500 and 1500 MUm increased after
the application for both formulations. This increase was statistically
significant at 1 and 3 h, when compared with T0. At 5 h no increases were seen in
the TDC for any of the formulations. When comparing the mean values of each time
evaluated, there is no statistically significant difference between the two
formulations at depth of neither 500 MUm nor 1500 MUm. TDC mean value to a depth
of 2500 MUm does not increase after the application of any of the formulations.
CONCLUSIONS: Hot and cold formulations are effective moisturizers; however, a
distinct profile was obtained for each. When water content averages were
compared, the effect of hot formulation in the superficial layers of the skin was
greater and longer in time than those of the cold formulation. On the other hand,
moisturizing formulations applied to the skin affected the dermis water content
until depth of 1500 MUm.
PMID- 25130770
TI - Heparin co-factor II enhances cell motility and promotes metastasis in non-small
cell lung cancer.
AB - Using the Serial Analysis of Gene Expression (SAGE) database from the Cancer
Genome Anatomy Project, we identified heparin co-factor II (HCII), which is over
expressed in non-small cell lung cancer (NSCLC). Here, we investigated the
clinical significance of HCII and provided molecular evidence to support the
suggestion that HCII could enhance cancer metastasis in NSCLC. We found that high
HCII expression in tumour tissue was associated with increased cancer recurrence
and shorter overall survival times in 75 clinically operable NSCLC patients. High
pretreatment plasma concentration of HCII was associated with reduced overall
survival in 57 consecutive NSCLC patients. We over-expressed and knocked down
HCII expression in lung cancer cell lines and confirmed that HCII could promote
cell motility, invasion ability and filopodium dynamics in NSCLC cells in vitro
and increased metastatic colonization in an in vivo mouse model. Exogenous
treatment of HCII promoted cancer cell migration, and this promigratory effect of
HCII was independent of thrombin. We further showed that HCII could up-regulate
cancer cell migration through the activation of PI3K, which acts upstream of Rac1
and Cdc42, and this effect could be blocked by heparin. We suggest that HCII is a
novel metastasis enhancer and may be used as a prognostic predictor for heparin
treatment in NSCLC.
PMID- 25130772
TI - The crystallization water of gypsum rocks is a relevant water source for plants.
AB - Some minerals, like gypsum, hold water in their crystalline structure. Although
still unexplored, the use of such crystallization water by organisms would point
to a completely new water source for life, critical under dry conditions. Here we
use the fact that the isotopic composition of free water differs from gypsum
crystallization water to show that plants can use crystallization water from the
gypsum structure. The composition of the xylem sap of gypsum plants during summer
shows closer values to gypsum crystallization water than to free soil water.
Crystallization water represents a significant water source for organisms growing
on gypsum, especially during summer, when it accounts for 70-90% of the water
used by shallow-rooted plants. Given the widespread occurrence of gypsum in dry
lands throughout the Earth and in Mars, these results may have important
implications for arid land reclamation and exobiology.
PMID- 25130771
TI - Development and application of molecular methods (PCR) for detection of Tasmanian
Atlantic salmon reovirus.
AB - Molecular (PCR) diagnostic tests for the detection and identification of
aquareovirus in general, and Tasmanian Atlantic salmon reovirus (TSRV)
specifically, were developed, and their diagnostic sensitivity and specificity
were determined and compared with virus isolation in cell culture.
Intralaboratory and interlaboratory comparison of PCR (conventional hemi-nested
RT-PCR & RT-qPCR) and virus isolation in cell culture using finfish cell lines,
CHSE-214 and EPC, was carried out for the detection and identification of TSRV
using field samples of farmed Atlantic salmon Salmo salar, L. from various
aquaculture sites around Tasmania. The interlaboratory comparison of diagnostic
methods was carried out between two laboratories, AAHL-CSIRO and DPIPWE-Tasmania.
A total of 144 fish from nine sites (12-33 fish per site) were sampled from two
regions of Tasmania (Tamar River estuary in the north and Huon River estuary in
the south-east) during late spring to early summer of 2009, and the data were
analysed using different statistical approaches. The prevalence of TSRV ranged
from 6% to 22% in both regions. All the diagnostic methods (data from both
laboratories) had high specificity, while the estimated sensitivity varied
between tests with RT-qPCR being the most sensitive (95.2%) method followed by
virus isolation and then conventional hemi-nested RT-PCR.
PMID- 25130773
TI - Effects of three hydrogen-rich liquids on hemorrhagic shock in rats.
AB - BACKGROUND: Hydrogen-rich saline provides a high concentration of hydrogen, which
selectively reduces levels of hydroxyl radicals and alleviates acute oxidative
stress in many models. We investigated the protective effects and mechanisms of
three different hydrogen-rich liquid resuscitation preparations on lung injury
induced uncontrolled-hemorrhagic shock (UHS) in rats. MATERIALS AND METHODS: A
UHS rat model was prepared using the method of Capone et al. of arterial bleeding
and tail amputation. Healthy male Wistar rats were randomly divided into seven
groups (10 per group) to receive: sham treatment; Ringer solution; hydrogen-rich
Ringer solution (H-Ringer solution); hydroxyethyl starch (HES); hydrogen-rich
hydroxyethyl starch (H-HES); hypertonic saline/hydroxyethyl starch (HSH); and
hydrogen-rich hypertonic saline/hydroxyethyl starch (H-HSH). At 72 h after
successful resuscitation, lung tissue was Hematoxylin Eosin stained to score any
pathologic changes. We also determined wet-to-dry (W/D) lung weight ratios and
lung tissue concentrations of interleukin (IL)-6, tumor necrosis factor (TNF)
alpha, IL-10, malondialdehyde (MDA), and superoxide dismutase (SOD) and
myeloperoxidase (MPO) activities. RESULTS: Compared with the non-H groups,
polymorphonuclear neutrophil accumulation in alveoli in the H groups was
significantly reduced (P value), and capillary leakage and wall edema were
ameliorated. Compared with the sham group, pathologic pulmonary injury scores,
W/D ratios, IL-6, TNF-alpha, IL-10, MDA concentrations, and MPO activity in the
other groups were all increased, whereas SOD activity was decreased (P < 0.01).
Comparing the H-Ringer, H-HES, and H-HSH groups respectively with the Ringer,
HES, and HSH groups, pathologic pulmonary injury scores, W/D ratios, IL-6, TNF
alpha, MDA concentrations, and MPO activity were all reduced, whereas IL-10
concentrations and SOD activity were increased (P < 0.01). CONCLUSIONS: Each
hydrogen-rich liquid resuscitation preparation could protect the lung against
acute injury secondary to UHS. These mechanisms may be associated with hydrogen
inhibiting the release of pro-inflammatory cytokines, promoting anti-inflammatory
cytokine release, and reducing oxidative damage.
PMID- 25130774
TI - Dakin solution alters macrophage viability and function.
AB - BACKGROUND: Macrophages are important in wound defense and healing. Dakin's
solution (DS), buffered sodium hypochlorite, has been used since World War I as a
topical antimicrobial for wound care. DS has been shown to be toxic to host
cells, but effects on immune cells are not well documented. MATERIALS AND
METHODS: DS at 0.5%, 0.125%, and ten-fold serial dilutions from 0.25%-0.00025%
were evaluated for cellular toxicity on murine macrophages (J774A.1). The effect
of DS on macrophage adhesion, phagocytosis, and generation of reactive oxygen
species was examined. Macrophage polarization following DS exposure was
determined by gene expression using quantitative real-time polymerase chain
reaction. RESULTS: Concentrations of DS >0.0025% reduced macrophage viability to
<5% in exposure times as short as 30 s. Similarly, phagocytosis of Staphylococcus
aureus, Pseudomonas aeruginosa, and Aspergillus flavus were significantly reduced
at all tested concentrations by macrophages pretreated with DS. H2O2 production
was reduced by 8%-38% following treatment with 0.00025%-0.125% DS. Macrophage
adherence was significantly increased with >0.0025% DS after 15 min of exposure
compared with controls. Quantitative real-time polymerase chain reaction
demonstrated that DS exposure resulted in classical macrophage activation, with
increased expression of inducible nitric oxide synthase 2, interferon-gamma, and
interleukin (IL)-1beta. CONCLUSIONS: DS at clinically used concentrations (0.025%
0.25%) was detrimental to macrophage survival and function. For optimal clinical
use, understanding the impact of DS on macrophages is important as depletion may
result in impaired pathogen clearance and delayed healing. These findings
indicate that 0.00025% DS is a safe starting dose; however, optimal use of DS
requires further validation with in vivo models.
PMID- 25130775
TI - Risk factors for late-onset neutropenia after rituximab treatment of B-cell
lymphoma.
AB - OBJECTIVES: Late-onset neutropenia after rituximab (RTX) therapy (R-LON) has been
widely reported, but clinical studies on a large number of cases are limited. In
this study, we aimed to investigate the incidence and risk factors of R-LON.
PATIENTS AND METHODS: In this study, we retrospectively analyzed data of 213
enrolled B-cell lymphoma patients (male 114; female 99) treated with RTX at a
single institution. R-LON was defined as otherwise unexplained grade III-IV
neutropenia after RTX. The median age of the patients was 62 years, and 129 of
them were initially diagnosed at advanced stages (stage III-IV). RESULTS: R-LON
occurred in 19 patients within a median of 121 (range, 49-474) days after the
last RTX administration. The 1-year cumulative incidence was 9.0%. On univariate
analysis, older age (>60 years), advanced stage, and purine analog or
methotrexate administration were significant or borderline significant risk
factors for R-LON, whereas sex, disease type, bone marrow invasion, combination
with cytotoxic chemotherapeutic drugs, intensified therapy (compared with R
CHOP), prior autologous transplantation, and repeated RTX administration were
not. On multivariate analysis, older age (hazard ratio (HR), 2.95) and advanced
stage (HR, 3.56) were significant risk factors. Treatment with granulocyte colony
stimulating factor was feasible in grade IV R-LON patients with high risk of
infection. DISCUSSION AND CONCLUSION: Careful follow-up is therefore necessary
after B-cell lymphoma treatment, especially in high-risk patients with advanced
disease or of older age.
PMID- 25130776
TI - 6-Bromoindirubin-3'oxime (BIO) decreases proliferation and migration of canine
melanoma cell lines.
AB - Despite recent therapeutic advances, malignant melanoma is an aggressive tumor in
dogs and is associated with a poor outcome. Novel, targeted agents are necessary
to improve survival. In this study, 6-bromoindirubin-3'-oxime (BIO), a
serine/threonine kinase inhibitor with reported specificity for glycogen synthase
kinase-3 beta (GSK-3beta) inhibition, was evaluated in vitro in three canine
melanoma cell lines (CML-10C2, UCDK9M2, and UCDK9M3) for beta-catenin-mediated
transcriptional activity, Axin2 gene and protein expression levels, cell
proliferation, chemotoxicity, migration and invasion assays. BIO treatment of
canine malignant melanoma cell lines at 5 uM for 72 h enhanced beta-catenin
mediated transcriptional activity, suggesting GSK-3beta inhibition, and reduced
cell proliferation and migration. There were no significant effects on invasion,
chemotoxicity, or apoptosis. The results suggest that serine/threonine kinases
may be viable therapeutic targets for the treatment of canine malignant melanoma.
PMID- 25130778
TI - Emotional perception and theory of mind in first episode psychosis: the role of
obsessive-compulsive symptomatology.
AB - The aim of the present study was to investigate the effects of comorbid obsessive
compulsive symptoms on emotional perception and theory of mind (ToM) in patients
with first-episode psychosis. Participants were 65 patients with non-affective
first episode psychosis (FEP) and 47 healthy controls. The patient group was
divided into two subgroups, those with (FEP+; n=38) and those without obsessive
compulsive symptomatology (FEP-; n=27). Emotion perception and ToM were assessed
with the Perception of Social Inference Test. Severity of psychotic and obsessive
compulsive symptoms was assessed with the Positive and Negative Syndrome Scale
(PANSS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), respectively.
Deficits in emotion recognition and theory of mind were confirmed in patients
with non-affective first-episode psychosis compared to healthy controls. In
patients, comorbidity with obsessive-compulsive symptoms was associated with
worse performance on certain aspects of social cognition (ToM 2nd order) compared
to FEP- patients. Our findings of impaired emotion perception and ToM in patients
with first-episode psychosis support the hypothesis that deficits are already
present at illness onset. Presence of OCS appears to have further deleterious
effects on social cognition, suggesting that these patients may belong to a
schizo-obsessive subtype of schizophrenia characterized by more extensive
neurobiological impairment.
PMID- 25130777
TI - Sensitivity of magnetic resonance imaging in the diagnosis of mobile and
nonmobile L4-L5 degenerative spondylolisthesis.
AB - BACKGROUND CONTEXT: Lumbar degenerative spondylolisthesis (LDS) is often
diagnosed by conventional supine magnetic resonance imaging (MRI). Numerous
studies have shown, however, that the degree of spondylolisthesis can be reduced
or disappears when the patient is supine as compared with standing lateral and
flexion-extension (SLFE) radiographs. PURPOSE: To compare the sensitivity of
supine MRI with SLFE radiographs in patients with L4-L5 LDS. STUDY DESIGN: A
retrospective imaging study. PATIENT SAMPLE: Included patients diagnosed with L4
L5 LDS with both SLFE films and supine MRI. METHODS: Lumbar degenerative
spondylolisthesis was defined radiographically as a slip greater than 4.5 mm.
Mobile LDS was defined as a difference of greater than 3% in slip percentage
between lateral radiographs and sagittal MRIs. Additional measurements included
L4-L5 facet effusion diameter on axial MRIs. Measurements were performed by two
independent examiners. The kappa coefficient was used to assess the interobserver
agreement. RESULTS: Of 103 patients assessed, 68% were women and the average age
was 66 years. Lumbar degenerative spondylolisthesis was seen on 101 (98%) lateral
films and 80 (78%) MRIs. Average slip was 10.0 mm for lateral standing
radiographs and 6.6 mm on MRI (p<.0001). Fifty (48%) patients were identified
with mobile LDS. The positive predictive value of facet joint effusion for mobile
LDS increased from 52% for effusions greater than 1 mm to 100% for effusions
greater than 3.5 mm. CONCLUSIONS: This study found that MRI had a sensitivity of
78% for detecting L4-L5 LDS compared with 98% for lateral standing films. We also
identified facet effusion size as a marker to predict mobile LDS. These findings
suggest that, particularly in the setting of facet effusions, the complete workup
of patients in whom LDS is possible should include standing radiographs.
PMID- 25130779
TI - Association between FYN polymorphisms and defense mechanisms in healthy Chinese
Han subjects.
PMID- 25130780
TI - An exploratory study of evoked facial affect in adolescent females with anorexia
nervosa.
AB - The aim of this exploratory study was to investigate facial affect in adolescent
females with anorexia nervosa (AN). Evoked facial affect was recorded whilst AN
and control participants (n=34) viewed emotional films. Significantly less facial
affect was found in AN adolescents, despite reporting no differences in
subjective emotion experience. These findings correspond with previous studies in
adults with AN. Altered facial affect may impair interpersonal functioning and
contribute to illness maintenance.
PMID- 25130781
TI - Differences in personality traits between male-to-female and female-to-male
gender identity disorder subjects.
AB - The present study aimed to investigate differences in personality traits among
male-to-female (MtF), female-to-male (FtM) gender identity disorder (GID)
subjects and non-transsexual male (M) and female (F) controls. Subjects were 72
MtF and 187 FtM GID subjects without psychiatric comorbidities together with 184
male and 159 female non-transsexual controls. Personality traits were assessed
using a short version of the Temperament and Character Inventory (TCI-125). Group
comparisons were made by two-way ANOVA. Statistical significances were observed
as follows: 1) lower novelty seeking in FtM than in M or MtF, 2) higher reward
dependence in FtM than in M, 3) higher cooperativeness in FtM than in M or MtF,
4) the highest self-transcendence in MtF among all the groups. The highest self
transcendence in MtF subjects may reflect their vulnerable identity and
constrained adaptation to society as the minority. Nevertheless, higher reward
dependence and cooperativeness in FtM subjects can be related to more determined
motivation for the treatments of GID and might promise better social functioning
and adjustment than MtF subjects.
PMID- 25130782
TI - Association between the 9 repeat allele of the dopamine transporter 40bp variable
tandem repeat polymorphism and Alzheimer's disease.
AB - A case-control study was performed to investigate the association between the
dopamine transporter (DAT) gene (SLC6A3) rs28363170 polymorphism and the risk for
Alzheimer's disease (AD). Our results indicated a statistically significant
correlation between the inheritance of the SLC6A3 9 repeat allele and the genetic
susceptibility to AD in a dose-dependent manner.
PMID- 25130783
TI - Why are you here again? Concordance between consumers and providers about the
primary concern in recurring psychiatric visits.
AB - Patient-centered care has become increasingly important over the last decade,
both in physical and mental health care. In support of patient-centered care,
providers need to understand consumers' primary concerns during treatment visits.
The current study explored what primary concerns were brought to recurring
psychiatric visits for a sample of adults with severe mental illness (N=164),
whether these concerns were concordant with those recognized by providers, and
which factors predicted concordance. We identified 17 types of primary concerns,
most commonly medications and symptoms, with only 50% of visits showing evidence
of at least partial agreement between consumers and providers. Contrary to
expectations, consumer demographics, activation, trust, and perceptions of
patient-centeredness were not predictive, while greater preferences for autonomy
predicted poorer agreement. Our findings highlight the need for interventions to
promote a shared understanding of primary concerns in recurring psychiatric
visits. Further attention is needed to ensure the provision of patient-centered
care such that consumer concerns are acknowledged and addressed within recurring
psychiatric visits.
PMID- 25130784
TI - Functional dyspepsia: outcome of focus groups for the development of a
questionnaire for symptom assessment in patients suffering from postprandial
distress syndrome (PDS).
AB - BACKGROUND: To date, no patient reported outcomes (PRO) instrument is available
for evaluation of treatment efficacy in functional dyspepsia (FD)/postprandial
distress syndrome (PDS). The aim of our study was to perform focus group
interviews for the development of a new questionnaire for assessing symptom
pattern and severity in PDS. METHODS: Random ambulatory patients diagnosed with
FD/PDS based on Rome III criteria and no predominant gastro-esophageal reflux
disease (GERD) symptoms were invited to participate. Focus group sessions were
organized where patients reported and discussed their symptoms, facilitated by an
experienced physician. After reaching saturation of identified symptom items,
questions for a pilot PRO instrument were drafted and evaluated in cognitive
interviews for relevance, clarity, and consistency. KEY RESULTS: Of 225 screened
patients, 26 patients were diagnosed with PDS without overlapping GERD as single
final diagnosis. Fifteen of these (87% female, 48 +/- 3.2 years) participated in
one of three focus groups. All (100%) confirmed experiencing symptoms that were
triggered or aggravated by ingestion of a meal, corresponding to early satiation
(100%), and postprandial fullness (100%). In addition reported gastroduodenal
symptoms were nausea (40%, postprandial in all, interprandial in 20%), upper
abdominal bloating (33%), excessive belching (27%), and vomiting (13%).
Epigastric pain and burning were present in respectively 20% and 13%. Non
gastroduodenal symptoms that patients reported included heartburn (33%, but
mostly sporadic), weight loss (93%, on average 5.0 +/- 1.7 kg), and fatigue
(67%). Questions evaluating these symptoms were validated in 15 cognitive
interviews. CONCLUSIONS & INFERENCES: This focus group study confirms symptoms
corresponding to postprandial fullness and early satiation as the key items for
developing a PRO for PDS.
PMID- 25130786
TI - Esophageal leukoplakia: a rare cause of white patches in esophagus with malignant
potential.
PMID- 25130785
TI - Isoselective ring-opening polymerization of rac-lactide initiated by achiral
heteroscorpionate zwitterionic zinc complexes.
AB - A highly isotactic stereoblock PLA has been obtained using the achiral
heteroscorpionate zwitterionic zinc complexes as catalysts, for the first time,
via a chain-end control mechanism.
PMID- 25130787
TI - Unilateral postural tremor caused by frontal cavernoma.
PMID- 25130788
TI - Analysis of biomarkers for risk of acute kidney injury after primary angioplasty
for acute ST-segment elevation myocardial infarction: results of the HORIZONS-AMI
trial.
AB - OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) may occur after
percutaneous coronary intervention (PCI). METHODS: We evaluated patients with ST
elevation myocardial infarction (STEMI) undergoing emergency PCI with serial
biomarkers. RESULTS: Of the 390 patients enrolled in the HORIZONS-AMI biomarker
substudy, 56 (14.3%) developed AKI. In the AKI group, the levels of B-type
natriuretic peptide were consistently higher than in the no-AKI group at baseline
(P = 0.0327), hospital discharge (P = 0.0002), 30-day follow-up (P = 0.0193), and
1-year follow-up (P = 0.031). At hospital discharge, the AKI group had elevated
biomarkers compared to the no-AKI group: D-dimer (P = 0.0066), C-reactive protein
(P = 0.0468), endothelial cell-selective adhesion molecule (P = 0.0169),
adiponectin (P = 0.0346), and von Willebrand factor (P = 0.0168); there was also
a trend toward higher cystatin C (P = 0.0585) in the AKI group. Similar
correlations between biomarker panel increase and the development of CI-AKI were
consistent at baseline, 30-day, and 1-year follow-up. Chemokine (C-C motif)
ligand 23 showed an opposite pattern with an increase at all time points in the
no-AKI compared to the AKI group. CONCLUSIONS: The risk of CI-AKI after primary
PCI for STEMI may be associated with hemostatic imbalances, activation of
procoagulants, decreased endogenous anticoagulants, enhanced inflammation,
platelet activation, or decreased fibrinolytic activity.
PMID- 25130789
TI - Prevalence and risk factors of sexual problems and sexual distress in a sample of
women suffering from chronic widespread pain.
AB - INTRODUCTION: Chronic widespread pain (CWP) is a prevalent musculoskeletal
problem and a cardinal symptom of fibromyalgia, affecting up to 15% of the
population. CWP is associated with substantial physical and psychological
impairment and reduced quality of life. AIM: To describe sexual problems in women
having CWP. To compare the sexual function between patients with CWP and healthy
women, and to explore potential predictors of sexual problems in women suffering
from CWP. METHODS: A descriptive, cross sectional study involving a total of 853
individuals, including 166 with CWP and 687 healthy counterparts. For the
screening of sexual problems and distress, the original and amended lifelong
version of the Female Sexual Function Index (FSFI) and the Female Sexual Distress
Scale were applied. A set of standardized questionnaires to assess potential risk
factors for sexual problems was further used. MAIN OUTCOME MEASURES: The levels
of sexual function and distress in women with CWP was compared with those of
healthy women. Univariate and multivariate linear regression was used to
determine the potential predictors for sexual problems in women with CWP and
healthy counterparts. RESULTS: Women with CWP reported more difficulties with
lubrication, more sexual pain, and higher levels of sexual distress. Potential
predictors of sexual problems in women with CWP were heterogeneous, with
relationship dissatisfaction being associated with lower levels of sexual
function in all the FSFI domains. Significant, domain-specific effects were
further detected for anxiety sensitivity, emotional intelligence, obsessive
compulsive behavior, and the big five personality traits. In general, factors
influencing recent sexual problems were different from those influencing lifelong
sexual function. CONCLUSIONS: CWP patients report more sexual pain and sexual
distress compared with controls. Assessment of sexual problems should therefore
be added to routine care of patients with CWP.
PMID- 25130790
TI - Mounier-Kuhn syndrome: a systematic analysis of 128 cases published within last
25 years.
AB - BACKGROUND AND AIMS: Mounier-Kuhn syndrome is a rare disease with abnormal
enlargement of major airways, but epidemiological studies are lacking, and
currently the most available data about it come from case reports, making it
difficult to collate changes in a particular patient to those in previously
published cases. The aim of this work is to systematically review cases published
in the last 25 years and to use descriptive statistics to summarize the patient
demographic and clinical information therein in order to acquire details about
patient clinical characteristics. METHODS: Cases published in world literature
between 1987 and 2013 were sought and reviewed according to PRISMA guidelines.
Cases were included only if patient's age was at least 18 years, and a computed
tomography scan with tracheal measurements was available. RESULTS: An 8:1 male
predominance was found in 89 identified reports (128 cases). Mean age was 53.9
years, and average tracheal diameter was 36.1 mm. No correlation between
increasing age and increasing tracheal diameter was found. Bronchiectasis,
tracheal diverticulosis and tracheobronchial dyskinesia were common (49.2%, 33.6%
and 28.9%, respectively). Cough, dyspnea and recurrent respiratory infections
(71.1%, 51.6% and 50.8%, respectively) were the most common complaints.
CONCLUSIONS: The data confirm that syndrome mostly manifests with nonspecific
respiratory symptoms and is significantly more common in males. Importantly,
there was no connection between age and airway diameter, a fact that could mean
that the enlargement does not progress over time, and its severity depends on
some other yet undetermined factors.
PMID- 25130791
TI - Stop adding metal layers: Will bioabsorbable scaffolds become the gold standard
for late in-stent restenosis and neo-atherosclerosis?
AB - The optimal management of instent restenosis has yet to be fully clarified. Drug
eluting balloons are a popular strategy, but a new stent is preferred when
dilatation gives a suboptimal result because of insufficient extrusion of
neointimal tissue. There is concern for adding multiple permanent metallic layers
to the vessel wall, especially in small vessels. The use of bioabsorbable
vascular scaffolds appears an appealing alternative strategy, since it scaffolds
the neointimal tissue without further adding metal struts to the vessel wall.
PMID- 25130792
TI - A comprehensive immunohistochemistry algorithm for the histological subtyping of
small biopsies obtained from non-small cell lung cancers.
AB - AIMS: Need for accurate histologic subtyping of non-small cell lung carcinomas
(NSCLCs) is growing. IHC patterns may be ambiguous in some cases, rendering it
difficult to determine subtypes. METHODS AND RESULTS: Tissue microarrays composed
of 184 resected NSCLCs were stained for TTF-1, Napsin A, CK7, p40, p63, CK5/6,
and mucicarmine. TTF-1 and Napsin A were chosen as the most accurate
adenocarcinoma (ADC) marker (ACM), and p40 as squamous cell carcinoma (SCC)
marker (SCM). We then prospectively performed IHC using these markers (TTF-1,
Napsin A, and p40) in a cohort of small NSCLC biopsies (n = 186) with ambiguous
morphology. Of these biopsies, 82.8% (154/186) were classifiable into either ADC
or SCC by applying '3-marker IHC panel'. Additional CK7, p63, and CK5/6 were
applied in 30 biopsies with equivocal IHC patterns, including 18 ACM-/SCM-
(double-negative) and 12 ACM+/SCM+ (double-positive) cases. Decision tree and
support vector machine models revealed that TTF-1 was a critical single marker
for ADC in double-positive cases (91.7% accuracy), whereas p63 and/or CK5/6
helped to subtype double-negative cases (72.2% accuracy). CONCLUSIONS: We propose
a novel comprehensive algorithm for subtyping NSCLCs using a 3-marker IHC panel
and additional p63 and CK5/6 that would be useful for subtyping small NSCLC
biopsies.
PMID- 25130794
TI - Footprints of cardiac mechanical activity as expressed in lung Doppler signals.
AB - AIMS: To determine the diagnostic information contained in cardiac pulsatile
pressure waves as expressed in the Doppler signals recorded over the right lung.
METHODS AND RESULTS: The pulsatile characteristics of the pulmonary vascular
system were studied by means of the novel pulse Doppler technology in 38 control
volunteers, 31 patients with atrial fibrillation (AF) and 7 patients with atrial
flutter. The Doppler velocity waveforms recorded were interpreted in relation to
the cardiac cycle mechanical events that generate them: Ventricular systole (S),
diastole (D) and presystolic left atrial contraction (A). It was demonstrated
that in all cases of AF, wave-A was absent. With longer diastole a high frequency
velocity waves were visible. It is assumed that they represent the atrial
mechanical fibrillation. In the patients with atrial flutter, the single A-wave
was replaced by a waveform termed F, the frequency of which exactly matched that
of the flutter wave on the ECG. The F-wave had both a positive and negative
component. CONCLUSION: The lung Doppler signals contain distinct signatures
typical of arrhythmias such as AF and atrial flutter that can be used for both
diagnosis and to gain insight into the nature of the phenomena.
PMID- 25130793
TI - Weight's up? Predictors of weight-related communication during primary care
visits with overweight adolescents.
AB - OBJECTIVE: Physicians' use of Motivational Interviewing (MI) techniques when
discussing weight with adolescent patients is unknown. METHODS: We coded audio
recorded encounters between 49 primary care physicians and 180 overweight
adolescent patients. During weight discussions, we used the MITI 3.0 to assess:
Empathy, MI Spirit, open-ended questions, reflections, MI consistent behaviors
(e.g., praising) and MI inconsistent behaviors (e.g., confronting). We examined
associations of patient and physician characteristics with (1) MI techniques, (2)
time discussing weight, and (3) encounter time. RESULTS: Physicians used more MI
consistent techniques with female patients (p=0.06) and with heavier patients
(p=0.02). Physicians with prior MI training also used more MI consistent
techniques (p=0.04) and asked more open-ended questions (p=0.05). Pediatricians
had a higher MI Spirit score than family physicians (p=0.03). Older patient age
was associated with physicians spending less time discussing weight-related
topics (p=0.04) and higher BMI percentile was associated with physicians spending
more time discussing weight-related topics (p=0.01). Increased use of MI
inconsistent techniques was associated with longer encounters (p=0.02).
CONCLUSION: Physicians' weight discussions vary based on adolescent and physician
characteristics. Importantly, not using MI lengthened encounter time. PRACTICE
IMPLICATIONS: Physicians might consider using MI techniques more and attempt to
use these equally with all adolescents.
PMID- 25130795
TI - High expression of Beclin-1 predicts favorable prognosis for patients with
colorectal cancer.
AB - PURPOSE: Beclin-1 is an autophagy gene. It promotes the formation of the
autophagic vesicle as well as plays an essential role in guarding the cells
against chromosomal instability. Overexpression of Beclin-1 has been reported to
predict a favorable survival in various cancers. However, little is known about
its prognostic significance in colorectal cancer. METHODS AND MATERIALS: A total
of three hundred and sixty-three (363) colorectal tissues from colorectal cancer
(CRC) patients were collected. Tissue micro-arrays and immunohistochemistry were
used to investigate the expression and prognostic significance of Beclin-1 in
CRC. The associations among Beclin-1 expression, clinicopathological parameters
and prognosis were evaluated. RESULTS: Beclin-1 had a higher expression in CRC
tissues than in normal tissues. A high expression of Beclin-1 was positively
correlated with gender (P=0.027), histological grade (P=0.003), pM status
(P=0.003) and clinical stage (P=0.024). Patients with a high Beclin-1 expression,
when compared to those with a lower expression had both a better overall survival
(OS, P=0.006) and disease-free survival (DFS, P=0.008). In the pT3 subgroup,
Beclin-1 was also found to be a good prognostic indicator (P<0.05). Multivariate
analysis showed a high expression of Beclin-1 was indeed a positive independent
prognostic factor of OS and DFS for CRC patients (P<0.05). CONCLUSION: Our
results demonstrated that a high expression of Beclin-1 correlated with a better
overall survival and disease-free survival, thus serving as a favorable
independent prognostic marker in CRC.
PMID- 25130796
TI - Aspirin may reduce liver fibrosis progression: Evidence from a multicenter
retrospective study of recurrent hepatitis C after liver transplantation.
AB - BACKGROUND AND AIMS: There is evidence for an association between thrombosis in
the hepatic microcirculation and liver fibrosis. The aim of this study was to
evaluate the role of daily low-dose aspirin (75 or 100mg, given for prevention of
hepatic artery thrombosis) in fibrosis progression to >= F2 fibrosis score in
liver-transplant recipients with recurrent hepatitis C virus (HCV). METHODS: All
HCV-positive patients who had undergone liver transplantation (LT) between 2000
and 2010 were included. Exclusion criteria were negative HCV RNA, previous LT or
death within a year of LT. Liver fibrosis was assessed by histological
evaluation. Data were censored at the date of the last histological evaluation
before starting anti HCV therapy. Progression to fibrosis F >= 2 was analyzed
with a multistate model with time-dependent covariables. RESULTS: One hundred and
eighty-eight patients were included. In univariate analysis, older recipient and
donor age, male donor gender, activity score >= A2 after LT, number of steroid
boluses and aspirin intake (HR: 0.75 [0.57-0.97]; P=0.03) influenced the risk of
progression to fibrosis >= F2. In multivariate analysis, adjusted on site, older
donor age, male donor gender, activity score >= A2 and number of steroids
boluses, remained independent predictors of fibrosis progression, while younger
recipient age and aspirin intake (HR: 0.65 [0.47-0.91]; P=0.01) were associated
with a slower fibrosis progression. CONCLUSION: Low-dose aspirin treatment might
be associated with a lower risk of liver fibrosis progression in patients with
HCV recurrence after LT.
PMID- 25130797
TI - [Progress and potential applications of induced pluripotent stem cell
technology].
AB - Differentiated somatic cells can be reprogrammed to a pluripotent state through
ectopic expression of specific transcription factors. These reprogrammed cells,
which were designated as induced pluripotent stem (iPS) cells, are detected to
exhibit unlimited self-renewal capacity and pluripotency. This breakthrough in
stem cell research provides a powerful and novel tool for the studies on
pathogenesis of diseases, reprogramming mechanism and development of new
therapies. For this reason, the iPSC technology has currently become one of the
hot topics in stem cells research. Recently, major progress in this field has
been achieved: initially, researchers succeeded in inducing the reprogramming of
mouse fibroblasts by retroviral transduction of four specific transcription
factors; in succession, the accelerated development of iPSC technology by
employing non-integrating viral vectors, non-viral vectors or removing the
introduced foreign genes via gene knock-out has ensured the yields of much safer
iPSC; meanwhile, some researches discovered the proofs that a number of micro
molecular compounds were potent in accelerating the cellular reprogramming. For a
prospect, iPSC are highly promising for regenerative medicine, disease modeling
and drug screening. In this review, the recent progress in the generation of
iPSC, prospects of their possible clinical applications and problems in the iPSC
research are summarized and discussed.
PMID- 25130798
TI - [Frequently ABL kinase domain G:C->A:T mutation and uracil DNA glycosylase
abnormal expression in TKI-resistant acute lymphoblastic leukemia of Chinese
population].
AB - Most Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL)
patients often show rapid recurrence and development of ABL kinase domain (KD)
mutation after tyrosine kinase inhibitor (TKI) treatment. To further investigate
the mechanism of Ph(+) ALL fast relapse after TKI treatment, ABL KD mutation in
35 Chinese Ph(+) ALL with TKI resistance was detected by direct sequencing. The
results showed that 77.1% (27/35) Ph(+) ALL patients with TKI resistance had ABL
KD mutation and 55.6% (15/27) Ph(+) ALL patients with ABL KD mutation had T315I.
Interestingly, 77.8% (21/27) Ph(+)ALL showed ABL mutation G: C->A:T, including
T315I, E255K and E459K. Furthermore, all the Ph(+) ALL patients with two or more
ABL KD mutations collaborated with complex chromosome abnormality and all the TKI
resistant Ph(+) ALL patients, whose karyotype progressed from simple t (9;22)
into complex, developed ABL KD mutation. Moreover, the expression level of uracil
DNA glycosylase UNG2, which inhibits G:C->A:T transition in genomic DNA,
decreased in Ph(+) ALL with TKI-resistance compared to that in newly diagnosis
Ph(+) ALL. It is concluded that there is a high frequent ABL KD G:C->A:T mutation
and a high genomic instability in Chinese TKI-resistant Ph(+) ALL. In addition,
the decreased UNG2 expression in TKI-resistant Ph(+) ALL probably contributes to
their high rate of ABL KD G:C->A:T mutation.
PMID- 25130800
TI - [Expression of G-CSFR IV isoform in adult acute myeloid leukemia and its clinical
significance].
AB - This study was aimed to investigate the expression of granulocyte colony
stimulating factor receptor IV(G-CSFR IV) in adult acute leukemia patients and
its clinical significance. The bone marrow hematopoietic stem cells from healthy
persons were used as controls. The real-time RT-PCR was used to determine the
expression level of G-CSFR I-IV in 99 AML, 34 ALL patients and 19 healthy
persons. The results showed that the relative expression level of G-CSFR IV/G
CSFR I in AML patients was obviously elevated, as compared with that in ALL
patients and controls, while the relative expression level of G-CSFR IV/G-CSFR I
in ALL patients showed no statistical difference from controls. The analysis of
clinical features and chemotherapeutic efficacy demonstrated that the clinical
remission rate in patients with high expression of G-CSFR IV/G-CSFR I was lower
than that in patients with low expression. The relative expression level of G
CSFR IV/G-CSFR I was not related with risk stratification from sex, age, blast
ratio, FAB typing, chromosome and fusion gene. It is concluded that the abnormal
high expression of G-CSFR IV relates with poor prognosis of AML.
PMID- 25130799
TI - [Effects of Sam68 gene silence on proliferation of acute T lymphoblastic leukemia
cell line Jurkat].
AB - This study was purpose to investigate the effect of Sam68 gene silence on
proliferation of human acute T lymphoblastic leukemia cell line Jurkat. The
sequence of shRNA targeting the site 531-552 of Sam68 mRNA was designed and
chemically synthesized, then a single-vector lentiviral, Tet-inducible shRNA
Sam68 system (pLKO-Tet-On) was constructed; next the Jurkat cells were infected
with lentivirus to create stable cell clones with regulatable Sam68 gene
expression. The inhibitory efficiency of Sam68 gene was assayed by Real-time PCR
and Western blot; the cell activity of Jurkat cells was detected with MTT assay;
the change of colony forming potential of Jurkat cells was analyzed by colony
forming test; the cell cycle distribution was tested by flow cytometry. The
results indicated that the expression of Sam68 in experimental cells was
statistically decreased as compared with that of the control cells; the cells
activity and colony forming capacity of the Jurkat cells with Sam68 gene silence
were significantly inhibited; with Sam68 gene silencing, the percentage of S
phase cells was significantly increased, while the percentage of G2 phase cells
was significantly decreased. It is concluded that the silencing Sam68 gene using
shRNA interference can effectively inhibit the proliferation of human acute T
lymphoblastic leukemia cell line Jurkat.
PMID- 25130802
TI - [Bioinformatic analysis of chronic myeloid leukemia progression and preliminary
experimental verification].
AB - This study was aimed to explore the progression mechanism of chronic myeloid
leukemia, so as to provide the new molecular markers for evaluation of CML
clinical outcome and selection of treatment. The microarray data of genes related
with progression from different phase of chronic myeloid leukemia (CML) were
collected from public data depository GEO (Gene expression datasets). SAM
analysis, fold change filtering, cross comparison were used to analyze the data
and identify different genes. Moreover, MeV and pSTIING sofewares were used to
analyze the key differential genes and signal pathways. At last, Q-PCR were used
to confirm the predicted key gene. The results indicated that after comparison, 9
genes were differentially expressed from AP to BC, and the integrin-mediated cell
adhesion , focal adhesion, regulation of actin cytoskeleton were the principal
pathways during CML progression. Network construction analysis found that AP
related genes or pathways may be the original signals; and MLLT4, WDR35 and EPHB4
were the key genes for CML progression. EPHB4 was confirmed by Q-PCR in CML BC
patients and CP patients. It is concluded that MLLT4, WDR35, EPHB4, integrin
mediated cell adhesion, focal adhesion and regulation of actin cytoskeleton are
the principal genes and pathways during CML progression.
PMID- 25130801
TI - [Construction of IK6 recombinant lentiviral vector and its expression and
biologic feature in THP1 cells].
AB - The purpose of this study was to construct a lentiviral vector carrying IK6 gene
and to observe the expression of IK6 as well as related biologic feature in THP1
cells, so as to provide an effective method to further investigate the role of
this gene in leukemia. The IK6 gene was obtained by using reverse transcription
polymerase chain reaction (RT-PCR). Then IK6 was recombined with the pGC-FU
vector to construct a recombinant lentiviral vector named pGC-FU-IK6 gene
GFP,which was confirmed by PCR and sequencing. The 293T cells were transfected
with pGC-FU- IK6-GFP by using Lipofectamine 2000. After examining the titer of
the virus, pGC-FU- IK6-GFP was used to transfect THP1 cells. The transfection
efficiency was detected by flow cytometry, and the expression level of mRNA and
IK6-GFP fusion protein were confirmed by RT-PCR and Western blot respectively.
Then the impact of IK6 on apoptosis and cell cycle was analyzed. The results
showed that the IK6 gene was obtained by RT-PCR and connected into the linearized
lentiviral vector to successfully constructed target plasmid named pGC-FU-IK6-GFP
with Amp resistant. The target plasmid was transfected into 293T cells and the
virus titer was 2.0*10(9)TU/ml. Next, THP1 cells were transfected with pGC-FU-IK6
GFP and the efficiency was up to 90%. The detection of the IK6 mRNA and IK6-GFP
fusion protein in target cells showed that IK6 could promote target cell clone
formation and inhibit apoptosis, but had no significant effect on the cell cycle.
It is concluded that virus vector carrying IK6 gene had been successfully
constructed and expressed in THP1 stably. Biology studies of target THP1 cell
shows that the IK6 is likely to interfere with the function of normal Ikaros
protein as tumor suppressor, and it exerts a potential anti-apoptotic effect.
Thus, IK6 can promote leukemia cell growth. However, there is no significant
effect on the cell cycle. It provides an effective method for exploring the
function of IK6 in acute myeloid leukemia.
PMID- 25130803
TI - [Comparison and analysis between CLL-hBMSC and N-hBMSC].
AB - This study was purpose to compare and analyze the chronic lymphocytic leukemia
human bone marrow stromal cells (CLL-hBMSC) and normal hBMSC (N-hBMSC) so as to
provide theoretical evidence for establishment of CLL-hBMSC interaction model to
imitate CLL microenvironment. Mononuclear cells (MNC) were isolated from bone
marrow of CLL patients and healthy donors and then were cultured, hBMSC were
established by expanding for at least five passages. The mRNA expression of
adhesion molecules, such as vascular cell adhesion molecule 1 (VCAM-1) and
intercellular adhesion molecule 1 (ICAM-1), was analyzed by real-time PCR. The
mRNA and protein expression of lymphotoxin beta receptor (LTbetaR) were
determined by real-time PCR and Western blot, respectively. The individual NF
kappaB members at protein level of CLL-hBMSC and N-hBMSC were examined by Western
blot. The effect of LTalpha1beta2 on individual NF-kappaB family members at
protein level in CLL-hBMSC and N-hBMSC was also examined by Western blot. The
death of CLL cells was determined by flow cytometry with PI staining when
cultured with or without CLL-hBMSC and N-hBMSC at different time points. The
results showed that the hBMSC could be established successfully from bone marrow
of CLL patients, which were similar to N-hBMSC. Adhesion molecules, such as VCAM
1 and ICAM-1, were found to be expressed at similar mRNA levels in CLL-hBMSC and
N-hBMSC. LTbetaR expressions at mRNA and protein levels were comparable between
CLL-hBMSC and N-hBMSC. The protein expression of the individual NF-kappaB family
members could be detected in CLL-hBMSC and N-hBMSC with similar expression
levels. LTalpha1beta2 stimulation activated both the classical ( RelA/p50 ) and
alternative ( RelB/p52 ) NF-kappaB complexes in CLL-hBMSC and N-hBMSC. The
capacities of CLL-hBMSC and N-hBMSC to protect CLL cell survival were similar. It
is concluded that there is no statistical difference between bone marrow from
healthy donors and CLL patients in the efficiency of generating of hBMSC. LTbetaR
NF-kappaB signaling molecules are expressed and activated on hBMSC with a similar
pattern.
PMID- 25130804
TI - [Expression of TFPI-2 gene and its promoter methylation in acute myeloid
leukemia].
AB - The aim of this study was to detect the mRNA expression of tissue factor pathway
inhibitor-2 ( TFPI-2) and its methylation in bone marrow mononuclear cells from
acute myeloid leukemia (AML) patients and to explore its significance in AML.
Bone marrow mononuclear cells were isolated from newly diagnosed AML patients (n
= 33), complete remission AML patients (n = 19), relapsed/refractory AML patients
(n = 12) and iron deficiency anemia patients (control group, n = 15). Expression
of TFPI-2 mRNA was detected with real-time quantitative PCR (RT-PCR) and the
methylation of CpG island in its promoter was detected with methylation-specific
PCR (MSP). The results showed that the expression of TFPI-2 mRNA in newly
diagnosed AML, complete remission AML and relapsed/refractory AML patients was
much lower than that in the controls (P < 0.05). Furthermore, its expression in
relapsed/refractory AML patients was lower than that in newly diagnosed AML
patients (P = 0.006). Compared with complete remission AML patients, the
expression of TFPI-2 mRNA in newly diagnosed AML patients was significantly
reduced (P = 0.030). The percentage of TFPI-2 promoter methylation in AML
patients was 64.63% (42/64). In newly diagnosed AML group, complete remission AML
group and relapsed/refractory AML group,the percentages of TFPI-2 promoter
methylation were 66.67% (22/33), 52.63% (10/19) and 83.33% (10/12) (P > 0.05),
respectively. The optical density ratio of TFPI-2 mRNA expression was 0.165
(0.005-2.099) in methylated AML patients, and 0.597 (0.011-2.787) in unmethylated
AML patients (P < 0.05). Methylation of TFPI-2 gene promoter was not detected in
control patients. After 2 courses of chemotherapy, the level of TFPI-2 mRNA was
much higher in the CR group than that in the non-CR group (P < 0.05). It is
concluded that the down-regulation or silence of TFPI-2 gene potentially results
from its promoter methylation, and the expression level of TFPI-2 and the
methylation status of its promoter may be used as indicators of risk
stratification and evaluation of disease progress.
PMID- 25130806
TI - [Anti-leukemia mechanism of miR-17 and miR-20a silencing mediated by miRNA
sponge].
AB - This study was aimed to quantitatively detect the expression levels of pre-miR-17
and pre-miR-20a in acute leukemia patients and eight kinds of leukemia cell
lines, and to investigate the anti-leukemia mechanism of miR-17 and miR-20a
silence mediated by miRNA Sponge. Quantitative real-time PCR was used to detect
the mRNA expression levels of pre-miR-17 and pre-miR-20a in patients with various
types of leukemia and leukemia cell lines. The Jurkat cells over-expressing miR
17 and miR-20a were transfected with recombinant lentivirus-transfecting units
targeted at miR-17 and miR-20a plus 6 ug/ml of polybrene. Then the proliferation
ability and cell cycle of Jurkat cells was evaluated by CCK-8 and flow cytometry
respectively. The results showed that the expression level of pre-miR-17 and pre
miR-20a in all leukemia patients was significantly higher than that in normal
group(P < 0.05), the expression of pre-miR-17 and pre-miR-20a in acute lymphoid
leukemia was significantly higher than that in acute myeloid leukemia(P < 0.05),
and the pre-miR-17 and pre-miR-20a expression level did not correlate
significantly with high white blood cell count>20.0*10(9)/L(P > 0.05). The miR-17
and miR-20a silencing mediated by miRNA Sponge led to a significant decrease of
cell growth, restored G1 accumulation and increase of cell apoptosis. It is
concluded that the expression of miR-17 and miR-20a is upregulated in leukemia
patients, which may contribute to leukemogenesis. Over-expressed miR-17 and miR
20a promote cell growth and cell cycle progression, and inhibit apoptosis through
negatively-regulating P21 and E2F1 after-transcriptionally.
PMID- 25130805
TI - [Expression of BCR/ABL fusion gene in circulating endothelial cells from chronic
myelogenous leukemia patients and its clinical significance].
AB - Several studies have shown that the tumor endothelial cells are different from
the normal tissue endothelial cells. These tumor endothelial cells may contribute
to tumor neo-vasculogenesis. This study was purposed to analyze the biologic
features and determine the expression level of CD133 and BCR/ABL fusion gene in
circulating endothelial cells (CEC) isolated from peripheral blood of CML
patients, as well as to investigate the role of CEC in disease progression.
Mononuclear cells were isolated from peripheral blood by density gradient
centrifugation; CEC were sorted by MACS and harvested in the endothelial growth
medium. The morphologic features of CEC were observed by microscopy, the cell
growth rate was calculated by cell counting, and the cells were identified by
immunofluorescence staining for the expression of CD31,CD34,VWF and CD133. The
expression of BCR/ABL fusion gene was examined by FISH in 12 CML patients. The
results indicated that the isolated CEC displayed the typical cobble-stone
morphology. These cells could be identified by the positive immunofluorescence
staining for CD31, CD34 and VWF, and showed more increased proliferative
potential as compared to that of healthy donors. It was found that the positive
rate of CD133 was 31.29% in CML patients, which was significantly different from
that of healthy donors (P < 0.05). In 12 CML patients, CEC carried the same
chromosome aberration as the leukemia cells (10.77%). Higher expression level of
CD133 and BCR/ABL fusion gene positively correlated with progression of disease.
It is concluded that the CEC may participate in invasion and angiogenesis in
patients with CML and possibly correlate to the spreading and progression of the
disease.
PMID- 25130807
TI - [Silence potentiates chemosensitivity of K562 cells to SAHA].
AB - Ribosomal protein S27a (RPS27a) can perform extra-ribosomal functions besides
imparting a role in ribosome biogenesis and post-translational modifications of
proteins. The RPS27a gene has been reported to be over-expressed in breast
fibroadenomas, colorectal and renal cancers, advanced-phase chronic myeloid
leukemia (CML) and acute leukemia (AL) patients. This study was purposed to
explore the function of RPS27a in CML-erythroleukemia cell line K562 cells.
RPS27a was silenced by short hairpin RNA (shRNA) in K562 cells. Furthermore, the
proliferation changes of K562 cells was detected by MTT method after silencing
the RPS27a with suberoylanilide hydroxamic acid (SAHA), then the IC50 of K562
sh1/sh2 and K562-scr cells to SAHA was measured. The results indicated that
compared with K562-scr cells, the IC50 of K562-sh1/sh2 to SAHA at 24 h and 48 h
decreased (P < 0.01); RPS27a silence significantly increased the percentage of
apoptotic K562-sh1/sh2 cells after incubation with 1 umol/L, 2 umol/L and 5
umol/L SAHA for 24 h and 48 h as compared with that of K562-scr cells (P < 0.01).
K562-sh1, K562-sh2 and K562-scr cells after incubation with or without 2 umol/L
SAHA for 48 h presented apoptosis features: i. e. chromatin condensation, nucleic
fragmentation and apoptotic body formation. It is concluded that RPS27a can
inhibit the apoptosis of K562 cells and RPS27a silence can potentiate sensitivity
of K562 cells to SAHA.
PMID- 25130808
TI - [Effects of As2O3 in combination with TPA on K562 cells].
AB - This study was aimed to investigate the effects of arsenic trioxide (As2O3)
combined with TPA on cell cycle, cell differentiation and apoptosis of K562 cell
line, and their possible mechanisms. K562 cells were treated with 200 nmol/L TPA,
2 umol/L As2O3 alone and 200 nmol/L TPA combined with 2 umol/L As2O3. The
proliferative inhibition rates were determined with CCK-8. Annexin V and agarose
gel electrophoresis were adopted to detect apoptosis. Colony formation test was
used to determine the colony-formation efficiency. Flow cytometry was used to
detect the cell differentiation and cell cycle changes. Western blot was employed
to detect the expression of P38 and p-P38 proteins. The results showed that
combination treatment had synergistic effects on the proliferative inhibition and
apoptosis, which were much higher than those treated alone. As2O3 could decrease
the colony formation ability of K562 cells. The cells treated with both TPA and
As2O3 expressed far more CD11b antigens compared with cells exposed to As2O3
alone. K562 cells treated with TPA were arrested in G1 phase compared with the
control group, As2O3 increased the percentage of K562 cells in the G2 phase. The
combination treatment increased the expression of p-P38 of K562 cells compared
with the cells exposed As2O3 alone. It is concluded that TPA can enhance the
effect of As2O3 on inducing apoptosis and adjusting cell cycle , which will
expect to provide a new therapeutic program.
PMID- 25130809
TI - [Clinical analysis of acute myeloid leukemia with t(8;21) (q22;q22) and loss of Y
chromosome].
AB - This study was aimed to investigate the clinical characteristics of acute myeloid
leukemia (AML) with t (8;21) (q22;q22) and loss of Y chromosomes. Clinical data
of 267 cases of AML were collected from January 2010 to June 2013. Among 267 AML,
there were 13 cases with t (8;21) (q22;q22) and loss of Y chromosomes. The
clinical data including clinical indicators, treatment protocols, curative effect
and prognosis were analyzed retrospectively. The results showed that after
normalized chemotherapy, there were 4 patients with complete remission at the
first cycle of treatment, 4 patients with complete remission at the second cycle,
4 patients with complete remission at the third cycle, but one patient without
complete remission after 4 cycles. There were 6 patients who did not relapse
during consolidation and intensive therapy. Among these 6 patients, 4 cases
accepted chemotherapy combined with transplantation, other 2 cases accepted
chemotherapy. In the remainder 6 patients, 4 cases relapsed once, one cases
relapsed twice, 1 cases relapsed for three times. Moreover, 2 cases who accepted
the chemotherapy and auto-hematopoietic stem cell trans-plantation, were
diagnosed as relapse, after accepted allo-hematopoietic stem cell
transplantation, currently are in disease-free status. In follow-up period, the
relapse-free survival (RFS) time was 4.67 +/- 3.45 months in chemotherapy group,
the RFS time is 34.17 +/- 21.37 months in chemotherapy and transplantation group.
The chemotherapy combined with transplantation extended the RFS time (P < 0.05).
It is concluded that the NCCN guide indicates that AML with t (8;21) ( q22;q22)
showed a good prognosis. but the clinical course of treatment confirmed that the
prognosis of AML patients with t (8;21) (q22;q22) and loss Y chromosomes is poor,
including uneasy remission and easy relapse, for improving the prognosis of these
patients, the hematopoietic stem cell transplantation should be recommended.
PMID- 25130810
TI - [Analysis of efficacy and prognosis of induction chemotherapy in 76 elderly
patients with acute myeloid leukemia (non-APL)].
AB - This study was purposed to investigate the clinical features, diagnosis,
treatment and prognosis of elderly patients with acute myeloid leukemia (AML)
(non-APL). The clinical data of 76 elderly ( >= 60 old years) AML (non-APL)
patients from January 2000 to January 2010 were analyzed retrospectively.
According to treatment methods,the 76 patients were divided into 2 groups:
induction chemotherapy group (51 cases) and best supportive treatment group (25
cases). The patients in induction chemotherapy group received the cytarabine
based induction chemotherapy regimens, including DA, MA, HA, IA and CAG; the
patients in best supportive treatment group received supportive treatment
including hydroxyurea, blood transfusion and so on. The clinical features,
diagnosis, treatment and prognosis between 2 groups were compared. The results
showed that the median survival times of patients in induction chemotherapy and
best supportive treatment groups were 5 (0.2-89) and 3 (0.1-17) months
respectively, there was significantly statistical difference in median survival
time between 2 groups(P < 0.01) suggesting that the induction chemotherapy
obviously prolonged the survival time of elderly CML patients. The 5 patients in
induction chemotherapy group survived more than 60 months, one of them survived
more than nine years. After the first cycle of chemotherapy, the complete
remission (CR) rate of patients was 19.6% (10/51), partial remission (PR) rate
was 19.6% (10/51), the overall response rate (ORR) was 39.2%, the mortality of
patients in induction remission stage was 13.7% (7/51) in induction chemotherapy
group; no 1 case in best supportive treatment group reached to CR. The CR rate of
patients by using MA regimen was 44.4% and its ORR was 55.5%, which was higher
than that by using DA, HA, IA and CAG regimens. The median chemotherapy cycles
were 3 (1-14). The follow-up found that the 3 months-survival rate of patients
was 65% and 42%, the 6 month-survival rate of patients was 43% and 21%, the 1
year-survival rate of patients was 29% and 13%, the 5 year-survival rate of
patients was 13% and 0% in induction chemotherapy and best supportive treatment
groups respectively, showing that the survival of patients in induction
chemotherapy group was better than those in best supportive treatment group. A
total of 31 of out 51 cases (60.8%) in induction chemotherapy group not response
to the first cycle of chemotherapy, the survival time of these patients was not
statistically significantly different from that of patients in best supportive
treatment group. It is concluded that the induction chemotherapy can
significantly improve the prognosis of elderly patients with AML, and prolong
their median survival time. The induction remission rate in elderly patients with
AML is lower than that of younger patients. The MA regimen is better than DA, HA,
IA and CAG, there is individual difference in the elderly patients with AML, If
the first cycle of chemotherapy has not reached to CR or PR, the best supportive
treatment may be considered. The low toxicity, efficient and well-tolerated
chemotherapy regimens may be chosen to prolong the survival time of the elderly
patients with AML (non-APL).
PMID- 25130811
TI - [Effect of SU11248 on leukemia cell line K562 and its molecular mechanisms].
AB - This study was aimed to investigate the effect of SU11248 on proliferation and
apoptosis of leukemia cell line K562 in vitro and its mechanism. The inhibitory
effect of 3.2 ug/ml SU11248 on K562 proliferation was tested by MTT assay. The
ability of SU11248 to induce apoptosis of K562 cells was examined by TUNEL and
DNA ladder. The expression of C-MYC, hTERT and BCR-ABL mRNA in K562 cells was
detected by RT-PCR. The protein expression of Akt and p-Akt in K562 cells was
detected by Western blot. The results showed that the proliferation of K562 cells
was obviously inhibited by 3.2 ug/ml SU11248 in a time-dependent manner. SU11248
could induce K562 cells apoptosis in dose-and time-dependent manner. The mRNA
expression of C-MYC, hTERT and BCR-ABL was reduced significantly by SU11248 in a
time-dependent manner (P < 0.05). Western blot detection showed that the
expression of p-Akt protein in K562 cells decreased in dose-and time-dependent
manner after SU11248 treatment, but the expression of Akt was not significantly
changed. It is concluded that SU11248 can inhibit the growth of K562 cells
efficiently through inducing apoptosis, its mechanism may be closely relate with
the expression down-regulation of C-MYC, hTERT, BCR-ABL and the inhibition of Akt
phosphorylation.
PMID- 25130812
TI - [Inhibitory effect of genistein on the proliferation of Raji cells and its
related mechanism].
AB - This study was aimed to investigate the anti-proliferative effect of genistein
(Gen) on BCL-6 positive Raji cells and its related mechanism. Trypan blue
staining and MTT method were used to analyze the anti-proliferative effect of Gen
on Raji cells. Cell apoptosis, protein expression and the interaction of BCL-6
and NCoR were detected by PI/AV dual staining, Western blot and Co-IP method,
respectively. The results showed that Gen had time- and dose-dependent inhibitory
effect on Raji cell proliferation and induced apoptosis. Different dose of Gen
had no significant effect on the expression of BCL-6 and NCoR, but could inhibit
the binding of BCL-6 and NCoR. It is concluded that Gen shows inhibitory effect
on BCL-6 positive lymphoma cells, which can be as a adjuvant therapy for combined
rituximab with chemotherapy.
PMID- 25130813
TI - [Analysis of the therapeutic efficacy and prognosis for acute myeloid leukemia
M2a patients treated by IA and DA regimens].
AB - This study was purposed to compare the therapeutic efficacy and prognosis of
acute myeloid leukemia M2a (AML-M2a) patients treated by idarubicin (IDA)
combined with cytarabine (Ara-C) (IA) and daunorubicin (DNR) combined cytarabine
(Ara-C) (DA) regimens. The clinical data of 65 patients with AML-M2a in our
hospital were collected from May 2009 to May 2013 and analyzed. The results
indicated the complete remission in IA group was slightly higher than that in DA
group, there was no statistically significant difference(P > 0.05); leukocyte
minimum value in IA group [(0.58 +/- 0.40)*10(9)/L] was obviously lower than that
in DA group [(0.99 +/- 0.67)*10(9)/L] (P < 0.05); neutrophil minimum value in IA
group [(0.19 +/- 0.09)*10(9)/L] was significantly lower than that in DA group
[(0.21 +/- 0.16)*10(9)/L] (P < 0.05); the neutropenia duration in IA group (12.59
+/- 5.31)d was much longer than that in DA group (9.17 +/- 7.04)d (P < 0.05). The
median survival time of patients in IA group was 36.67 months, which was
obviously longer than that of patients in DA group (21.45 months) (P < 0.05). The
lactate dehydrogenase (LDH) value and chemotherapy regimens were the
independently risk factor affecting the prognosis of AML-M2a patients. It is
concluded that as compared with DA regimen, the IA regimen can prolong the median
survival time and has better long-term therapeutic efficacy, thus it can be used
as the first chemotherapy regimen for treatment of AML-M2a.
PMID- 25130814
TI - [Association of XRCC1 genetic polymorphism with susceptibility to non-Hodgkin's
lymphoma].
AB - The purpose of this study was to explore the association between X-ray repair
cross-complementing group 1 (XRCC1)gene polymorphism and non-Hodgkin's lymphoma
risk. A total of 282 non-Hodgkin's lymphoma (NHL) patients and 231 normal
controls were used to investigate the effect of three XRCC1 gene polymorphisms
(rs25487, rs25489, rs1799782) on susceptibility to non-Hodgkin's lymphoma.
Genotyping was performed by using SNaPshot method. All statistical analyses were
done with R software. Genotype and allele frequencies of XRCC1 were compared
between the patients and controls by using the chi-square test. Crude and
adjusted odd ratios and 95% confidence intervals were calculated by using
logistic regression on the basis of genetic different models. For four kinds of
NHL, subgroup analyses were also conducted. Combined genotype analyses of the
three XRCC1 polymorphisms were also done by using logistic regression. The
results showed that the variant genotype frequency was not significantly
different between the controls and NHL or NHL subtype cases. Combined genotype
analyses of XRCC1 399-280-194 results showed that the combined genotype was not
associated with risk of NHL overall, but the VT-WT-WT combined genotype was
associated with the decreased risk of T-NHL (OR: 0.21; 95%CI (0.06-0.8); P =
0.022), and the WT-VT-WT combined genotype was associated with the increased risk
of FL(OR:15.23; 95%CI (1.69-137.39); P = 0.015). It is concluded that any studied
polymorphism (rs25487, rs25489, rs1799782) alone was not shown to be rela-ted
with the risk of NHL or each histologic subtype of NHL. The combined genotype
with mutation of three SNP of XRCC1 was not related to the risk of NHL. However,
further large-scale studies would be needed to confirm the association of
decreased or increased risk for T-NHL and FL with the risk 3 combined SNP mutants
of XRCC1 polymorphism.
PMID- 25130815
TI - [Interaction between tumor-associated macrophages (TAMs) and HUT-78 lymphoma
cells].
AB - This study was aimed to explore the effects of lymphoma cells on the
differentiation of monocytes from peripheral blood to tumor-associated
macrophages (TAM) and the effect of TAM on proliferation of lymphoma cells in
vitro, and investigate the difference between newly diagnosed lymphoma patients
and healthy volunteers. Blood samples were obtained from 15 newly diagnosed
lymphoma patients and 8 healthy volunteers. Monocytes from peripheral blood were
isolated by Ficoll- Hypaque density gradient centrifugation and CD14 immuno
magnetic beads. Then monocytes were directly co-cultured with HUT-78 lymphoma
cells by using Transwell apparatus in vitro. Expression of the markers of TAM
(CD68 and CD163) were detected by flow cytometry to analyse the proportion of
differentiated TAM. Growth curve of HUT-78 cells was made by direct cell count.
The IL-10 and VEGF levels in the co-culture system were detected by ELISA. The
detection results of newly diagnosed lymphoma patients were compared with that of
healthy controls. The results showed that the proportion of CD68(+), CD163(+) and
CD68+CD163 (+) cells were significantly up-regulated after co-cultured with HUT
78 lymphoma cells in both patients and healthy controls (P < 0.05). There was no
statistical significance in the increasing degree between patients and healthy
controls. TAM differentiated from peripheral blood monocytes showed no
significant promotion or inhibition on the growth of co-cultured lymphoma cells.
For patients, the IL-10 and VEGF levels in the co-culture group were
significantly lower than those in two single culture groups (P < 0.05) . For
healthy controls, there was no significant difference between these two. It is
concluded that lymphoma cells can promote the differentiation of monocytes to
macrophages with M2-like phenotype. There is no difference in the promoting
degree between patients and healthy controls. TAM differentiated from patients'
monocytes significantly down-regulate levels of IL-10 and VEGF in the co-culture
system, exhibited functions more like M1 macrophages. In contrast, TAM
differentiated from monocytes of healthy controls show no such effects on the co
culture system.
PMID- 25130816
TI - [Clinical analysis of lymphoblastic lymphoma/leukemia treated with Hyper-CVAD/MA
regimen chemotherapy combined with haploidentical hematopoietic stem cell
infusion].
AB - This study was aimed to investigate the efficacy of Hyper-CVAD/MA regimen
chemotherapy combined with haploidentical hematopoietic stem cell infusion for
the treatment of lymphoblastic lymphoma/leukemia (LBL/ALL). Seven patients with
LBL/ALL were treated in Second Artillery General Hospital from August 2009 to
September 2012. All patients received programmed infusions of granulocyte-colony
stimulating factor (G-CSF)-mobilized family related HLA-haploidentical donor
peripheral blood hematopoietic stem cell (G-PBHSC) after each of cycle of Hyper
CVAD/MA regimen chemotherapy without graft-versus-host disease (GVHD)
prophylaxis. A total of four cycles of therapy were planned. The interval between
each cycle of treatment was 8 to 12 weeks. By April 2014, the median follow-up
time was 41 (20-57) months. The results showed that the 7 patients totally
received 30 cycles of treatment, and all patients achieved complete remission
(CR). The patients were generally well-tolerated to therapy, and the most
significant toxicities of grade 3 to 4 neutropenia and thrombocytopenia developed
in nearly all of the patients after each course of the Hyper-CVAD/MA regimen. No
GVHD was observed in any of the patients during treatment. Up to now, 5 patients
were still alive, 2 patients were died of relapse. It is concluded that the
combination of chemotherapy and programmed haploidentical G-PBHSC infusion is a
promising approach to the treatment of LBL/ALL.
PMID- 25130817
TI - [Clinical analysis of 202 cases of extranodal NK/T-cell lymphoma].
AB - This study was purposed to explore the therapeutic strategy and factors
influencing prognosis through the analysis of clinical characteristics, genetic
aberrations, treatment and prognosis of the patients with extranodal NK/T cell
lymphoma (ENKTL). A total of 202 patients with ENKL from 2005-2013 were analyzed
retrospectively in term of Ann Arbor stage, B symptoms, lactate dehydrogenase
(LDH), international prognostic index (IPI), beta2-microglobulin and the
expression of MYC,HXO11,BCL-2. The survival was analyzed using Kaplan-Meier
method, and the COX regression model was employed for multivariate analysis. The
results showed that the 5 year overall survival (OS) rate and event-free survival
(EFS) rate were 61.9% and 53.9% respectively; chemoradiotherapy was apparently
better than chemotherapy alone for OS and EFS; OS and EFS of the patients with
BCL-2 expression were apparently better than patients without BCL-2 expression;
multivariant analysis by COX regression showed that Ann Arbor stage and BCL-2
expression were independent prognostic factors for EFS/OS. It is concluded that
chemoradiotherapy is better than chemotherapy alone for treatment of ENKL. Ann
Arbor stage and BCL-2 expression are independent prognostic factors.
PMID- 25130818
TI - [Efficacy of liver transplantation for acute hepatic failure caused by
reactivation of hepatitis B virus infection after chemotherapy and radiotherapy
for diffuse large B-cell lymphoma].
AB - This study was aimed to investigate the morphological, biological ,clinical and
therapy features in a special case of primary gastric non-Hodgkin's lymphoma (PG
NHL) through analysis of PG-NHL patient who developed fulminating hepatitis
following chemotherapy and radiotherapy and thus received liver transplantation
(LT). The morphological changes of cells were analyzed by bone marrow smear, the
expression and mutation of abnormal genes were detected by nested multiplex PCR,
and HBV-DNA copies were detected by real-time fluorescence quantitative PCR (FQ
PCR). The results showed that at onset of disease, patient was diagnosed as
primary gastric non-Hodgkin's lymphoma (PG-NHL) with HBsAg(+) and HBVDNA(-).
LUGANO stage was Ia. aaIPI score was 0.The patient was treated with R-CHOP
regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone),
rituximab maintenance treatment and radiotherapy. During the treatment, the
patient has taken entecavir, 1 week later after the radiotherapy (2 months later
after the chemotherapy), then the entecavir was discontinued. Six months later
HBV DNA(+), the progressive acute hepatic failure (AHF) happened to the patient,
who thus received phylogenetic right liver transplantation (LT). He has survived
for 3 years after LT so far. The liver function of patient was normal more than 3
years after LT. The patient was checked regularly by PET-CT, and his PG-NHL
continue complete remission(CR). It is concluded that the patients receiving
chemotherapy or immunosuppressive therapy should be screened for HBV DNA, liver
function and HBV reactivation signs. HbsAg positive patients should receive
preventive antiviral therapy. After chemotherapy or immunosuppressive therapy,
the patients should be given antiviral maintenance therapy, and the liver damage
should receive the hepatoprotective and effective support treatment, LT is
necessary and feasible to obtain long-term survival.
PMID- 25130819
TI - [Inhibitory effect of pumpkin protein on expression of Notch signal in RPMI8226
myeloma cells].
AB - This study was aimed to explore the inhibitory effect of pumpkin protein
(cucurmosin, CUS) on proliferation of RPMI8226 myeloma cells in vitro and its
mechanism. Western blot was used to detect the expression level of Notch-1,
Jagged-2, P-Akt and NF-KB in the myeloma cells treated by different
concentrations of CUS. The results demonstrated that CUS could down-regulate the
protein expression levels of Notch1, Jagged-2, P-Akt and NF-KB in the myeloma
cells and with time-and concentration-dependent way, at the same time CUS could
also decrease the expressions of BCL-2 and P-Akt. It is concluded that CUS can
obviously inhibit the RPMI8226 cell proliferation in vitro, down-regulate the
expression levels of Notch signal and its down-stream target genes. Therefore,
Notch signaling pathway can be used as a new treatment target for multiple
myeloma, and CUS may be become a potential new drug for regulating Notch
signaling pathway.
PMID- 25130820
TI - [Apoptosis-inducing effect of valproic acid combined with arsenic trioxide on
RPMI 8226 cells and its mechanism].
AB - This study was aimed to investigate the apoptosis-inducing effect of valproic
acid (VPA) combined with arsenic trioxide (ATO) on human multiple myeloma RPMI
8226 cells and its mechanism. The cell proliferation of RPMI 8226 cells was
assayed by CCK-8 method. The cell apoptosis were detected by flow cytometry.
Semiquantitative RT-PCR and Western blot were applied respectively to detect the
mRNA and protein expression level of BCL-2, BAX, caspase-8 and caspase-9 gene.
The results showed that both the VPA and ATO inhibited RPMI 8226 cell
proliferation. The combination of ATO and VPA has synergistic effect (Q values
greater than 1.15). The RPMI 8226 cell apoptosis rate in combined drug group was
significantly higher than that in single drug group (P < 0.05). The mRNA and
protein expressions of BCL-2 gene in combined drug group decreased, while the
mRNA and protein expressions of BAX, caspase-8 and caspase-9 significantly
increased, compared with single drug group (P < 0.05) . It is concluded that VPA
can enhance the sensitivity of RPMI 8226 cells to ATO-induced apoptosis, which
may be associated with decreasing the BCL-2 expression and increasing the BAX,
caspase-8 and caspase-9 gene expression.
PMID- 25130821
TI - [JAK2V617F mutation and TNF-alpha expression in myeloproliferative neoplasms and
their correlation].
AB - This study was aimed to explore the JAK2V617F mutation and TNF-alpha expression
in patients with myeloproliferative neoplasm (MPN), and the relation between them
so as to provide theoretical basis for clinical practice and target therapy.
Sixty-two confirmed BCR-ABL-negative MPN patients and 15 healthy adults were
enrolled in this study. The peripheral blood mononuclear cells of the patients
and healthy controls were divided into two parts, one part was used to extract
DNA, the other one was used to extract mRNA and reverse-transcribe into cDNA.
Real-time fluorescent quantitative PCR was used to detect JAK2V617F mutation
proportion and the expression level of TNF-alpha. The results showed that the
positive rate of JAK2V617F mutation in MPN patients was 64.52% (40/62) ,
including 54.28% in essential thrombocythemia (ET) patients (19/35), 94.74% in
polycythemia vera (PV) patients (18/19) and 37.50% in myelofibrosis (MF) (3/8)
patients. Mutation proportions of JAK2V617F in ET, PV and MF patients were 0.838
+/- 0.419, 4.417 +/- 0.658, 2.746 +/- 2.009 respectively. The expression of TNF
alpha in ET, PV and MF patients were higher than that in healthy controls: 1.7,
7.0, 8.2-fold (P < 0.05) respectively. In addition, TNF-alpha expression was
correlated with JAK2V617F allele burden (Pearson r = 0.610,R(2) = 0.372,P =
0.005). It is concluded that TNF-alpha plays an important role in the
pathogenesis of MPN, the TNF-alpha expression increases and is different in ET,PV
and MF patients,which correlates with JAK2V617F allele burden.
PMID- 25130823
TI - [Role of Toll-like receptor 2 in primary immune thrombocytopenia].
AB - The aim of this study was to explore the role of Toll-like receptor (TLR) 2 in
primary immune thrombocytopenia (ITP) by detecting TLR2 expression in the
peripheral blood lymphocytes of patients with ITP and evaluating the role of TLR2
activation on inflammatory cytokine secretion. A total of 39 ITP patients and 21
normal controls were enrolled in this study. The expression of TLR2 was detected
by real-time PCR and flow cytometry, and the concentration of IL-6 and TNF-alpha
in culture supernatant of PBMNC treated with pam3CSK4 for 48 hours were detected
by ELISA. The results showed that the expression of TLR2 mRNA in active ITP
patients (3.561 +/- 0.741) was significantly higher than that in normal controls
(1.750 +/- 0.314) (P < 0.05), but there was no statistically significant
difference between remission ITP patients (2.333 +/- 0.448) and normal controls
(P > 0.05) . Flow cytometry analysis found that the TLR2 was not expressed on T
and B cells, but expressed on all monocytes both from ITP patients and normal
controls. Further activation experiment showed that TLR2 activation in vitro
could induce the expression of IL-6 (1644 +/- 634.0 vs 4111 +/- 525.2 pg/ml) and
TNF-alpha (75.37 +/- 22.31 vs 326.0 +/- 109.9 pg/ml) in PBMNC from ITP patients
(both P < 0.05), but just could promote IL-6 expression in normal controls (2119
+/- 636.9 vs 4671 +/- 315.9 pg/ml)(P < 0.05). It is concluded that the expression
of TLR2 mRNA is up-regulated in PBMNC of ITP patients, and this increased TLR2
maybe participate in ITP through inducing secretion of inflammatory cytokines.
PMID- 25130822
TI - [Iron chelation therapy and its influence on the alleviation of EPO resistance in
MDS patients].
AB - This study was aimed to investigate the changes of erythropoietin (EPO),
hemoglobin(Hb) and recombinant EPO (rEPO) levels in MDS patients receiving iron
chelation therapy, and to explore the relationship between EPO and serum
ferritin(SF). A total of 172 MDS patients and 30 healthy controls were studied.
The levels of SF, EPO, serum iron (SI), total iron binding capacity (TIBC), C
reaction protein (CRP) and Hb were measured respectively, the level of SF was
adjusted according to the changes of CRP. Among them, there were 34 cases of low
risk (SF>1 000 mg/L) receiving deferoxamine therapy, whose changes of SF, EPO,
SI, TIBC, Hb levels were detected and compared before and after treatment.
Besides, the difference in the incidence of EPO resistance in iron overload group
and non-iron overload group was assessed before and after therapy, and 58 cases
of low-risk and EPO<1 000 U/L MDS patients were given rEPO therapy. The results
showed that the level of EPO in non-iron overload group was higher than that in
the normal control group (997.44 +/- 473.48 vs 467.27 +/- 238.49, P < 0.05).
Obviously, the level of EPO in iron overload group was higher than that in non
iron overload group and control group (3257.59 +/- 697.19 vs 997.44 +/- 473.48, P
= 0.012, 3257.59 +/- 697.19 vs 467.27 +/- 238.49, P = 0.002). Otherwise, the
incidence of EPO resistance in iron overload group was higher than that in non
iron overload group (18/35 vs 2/23, P = 0.001), and the level of EPO and SF was
positively related to each other in iron overload group (r = 0.310,P = 0.036).
After receiving iron chelation therapy, the levels of SF, SI, TIBC and EPO in
iron overload group were significantly lower than that before therapy (3942.38 +/
641.82 vs 2266.35 +/- 367.31, P = 0.028;48.61 +/- 10.65 vs 28.52 +/- 12.61, P =
0.034;59.84 +/- 12.62 vs 33.76 +/- 15.43, P = 0.045;3808.01 +/- 750.22 vs 1954.78
+/- 473.18, P = 0.042). Moreover, the level of Hb increased (35 +/- 18 vs 57 +/-
21, P = 0.046) and the EPO resistance in some patients was decreased. It is
concluded that iron chelation therapy can improve the efficacy of EPO to
alleviate EPO resistance in patients wtih anemic MDS, decrease the pathological
level of EPO, enhance Hb levels and reduce the dependency on blood transfusion.
PMID- 25130824
TI - [Expressive changes of CD4(+)T cell subset transcription factors in patients with
aplastic anemia, myelodysplastic syndrome and acute myeloid leukemia and their
clinical significances].
AB - This study was aimed to compare the expressions of specific transcription factors
of CD4(+) T cell subset ( T-bet, GATA-3, RORgammat and FoxP3 mRNA) in peripheral
blood of patients with aplastic anemia(AA), myelodysplastic syndrome(MDS), and
acute myeloid leukemia(AML), and investigate their immune status and
pathogenesis, so as to provide experimental basis for the choice of clinical
treatment. The expression of T-box (T-bet), GATA-3, ROR-gammat and Foxp3 mRNA in
PBMNC were examined by RT-PCR in 42 cases of MDS, including 22 refractory
anemia(MDS-RA) and 20 refractory anemia with excess blasts (MDS-RAEB), in 23
cases of AA, 17 cases of AML patients and 16 healthy volunteers respectively. The
results indicated that, compared with normal control group, expressions of T-bet
and RORgammat mRNA in AA patient group were significantly higher (P < 0.01),
expression levels of GATA3 Foxp3 mRNA were lower (both P < 0.01). There was no
significant difference in expression of T-bet and GATA3 mRNA between MDS group
and normal control group, but the expression levels of Foxp3 and RORgammat mRNA
were higher than those in normal controls (P < 0.05); T-bet and RORgammat in MDS
RA group were higher than those in the normal controls(P < 0.01), and GATA3
expression significantly reduced (P < 0.05), however, there was no significant
difference in expression of Foxp3 between MDS-RA and the controls. Expression
levels of T-bet and RORgammat mRNA in patients with MDS-RAEB and AML were lower
than those in normal controls (P < 0.05), but the expression levels of GATA3 and
Foxp3 mRNA were significantly higher than those in normal controls (P < 0.01). It
is concluded that the transcription factor expressions are different in PBMNC of
patients among these three diseases. Immune-mediated excessive apoptosis may play
an important role in pathogenesis, bone marrow failure in patients with AA and
MDS-RA, and abnormal clones of immature cells may be one of main reasons for bone
marrow failure in AML and late stage of MDS.
PMID- 25130825
TI - [Abnormal quantity of regulatory T cells in peripheral blood of patients with
severe aplastic anemia and its clinical significance].
AB - This study was purposed to investigate the role of regulatory T cells (Treg) in
the immune unbalance for patients with acquired severe aplastic anemia (SAA). The
flow cytometry was used to detect the quantity of CD4(+) CD25(+) CD127(dim)
Tregs, T cell subset (CD4(+)/CD8(+) ratio), dendritic cell(DC) subset(mDC/pDC
ratio) in 44 SAA patients(25 untreated patients and 19 recovery patients) and 23
normal controls. The correlation between Tregs and T cell subset, DC subset and
hemogram were analyzed. The results showed that the percentage of CD4(+) CD25(+)
CD127(dim) Tregs in peripheral blood lymphocyte(PBL) of untreated patients was
(0.83 +/- 0.44) %, which was obviously lower than that in recovery patients (2.91
+/- 1.24)% and normal controls (2.18 +/- 0.55)% (P < 0.05), but the difference
was not statistically significant between latter two groups. The ratio of
CD4(+)/CD8(+) was (0.5 +/- 0.3) in untreated patients, which was obviously lower
than that in recovery patients (1.2 +/- 0.4) and normal controls (1.11 +/- 0.24)
(P < 0.05). The ratio of mDC/pDC was (3.08 +/- 0.72) in untreated patients, which
was significantly higher than that in recovery patients(1.61 +/- 0.49) and normal
controls (1.39 +/- 0.36) (P < 0.05). The percentage of CD4(+) CD25(+)CD127(dim)
Tregs in PBL positively correlated with CD4(+)/CD8(+) ratio (r = 0.695, P <
0.01), and that negatively correlated with mDC/pDC ratio (r = -0.796, P < 0.01).
There were significant positive correlations between CD4(+)CD25(+)CD127(dim)
Tregs/PBL and WBC, Ret% (r = 0.761, 0.749 respectively, P < 0.01). It is
concluded that the decrease of CD4(+)CD25(+)CD127(dim) Tregs quantity in SAA may
be one of mechanisms underlying bone marrow failure resulting from the
deterioration of immune tolerance and hyperfunction of T-cells.
PMID- 25130826
TI - [Safety and effectiveness of tumor-ablative chemotherapy combined with low
intensity modified conditioning regimen for 30 patients with hematologic
malignancies receiving allogeneic hematopoietic stem cell transplantation].
AB - This study was aimed to investigate the safety and effectiveness of tumor
ablative Chemotherapy combined with low intensity conditioning regiment
BUCy/TBICy for patients with hematologic malignancies receiving allogeneic
hematopoietic stem cell transplantation (allo-HSCT). The clinical data of 30
patients with hematologic malignancies received above-mentioned therapeutic
method from January 2012 to January 2013 was analyzed retrospectively, and the
engraftment, GVHD, infection, conditioning-related toxicity, relapse and survival
rates were evaluated. All the patients signed the informed consent before
transplantation. The median follow-up duration was 20.5 (16.3-27.3) months. The
results indicated that all the patients had been engrafted successfully. One year
overall survival (OS) and disease-free survival (DFS) rates were 93.3% and 83.3%
respectively. No conditioning-related toxicity occurred. The incidences of II-IV
grade aGVHD was 37.9%, among which incidence of III-IV grade aGVHD was 3.4%;
incidence of extensive cGVHD was 13.8%. So far, 1 case relapsed, 1 case displayed
graft rejection, and poor function of graft occurred in 1 case, death occurred in
2 cases(6.7%). It is concluded that tumor-ablative chemotherapy combined with low
intensity-modified BUCy/TBICy is safe and effective in allogeneic hematopoietic
stem cell transplantation for hematologic malignancies, and it is useful to
reduce relapse of hematologic malignancies after transplantation.
PMID- 25130827
TI - [Transplantation of umbilical cord mesenchymal stem cells combined with
haploidentical hematopoietic stem cells for 36 patients with refractory/relapsed
myeloid leukemia].
AB - This study was purposed to analyse the clinical efficacy of transplantation of
umbilical cord mesenchymal stem cells (UC-MSC) combined with haploidentical
hematopoietic stem cells (haplo-HSCT) for patients with refractory/relapsed
myeloid leukemia. The clinical data of 36 patients received transplantation of UC
MSC combined with haplo-HSCT from January 2007 to June 2013 were summarized
retrospectively, the engraftment, GVHD and 2 years-overall survival (OS) were
analysed. The results showed that the median times of neutrophil
count>0.50*10(9)/L and platelet count>20*10(9)/L were 12.0 days and 14.0 days,
respectively. Grade III to IV aGVHD occurred in 5 out of 36 patients (13.8%).
cGVHD occurred in 12 out of 32 patients (37.5%) and extensive cGVHD occurred in 2
patients. Additionally, only 3 patients (8.3%) experienced relapse. The 2-year OS
rate of patients was 76.9%. It is concluded that the transplantation of UC-MSC
combined with haplo-HSCT has good therapeutic efficacy for patients with
refractory/relapsed myeloid leukemia, and may be served as a therapeutic method
especially for patients with high risk and without well matched donor.
PMID- 25130828
TI - [Allogeneic hematopoietic stem cell transplantation for chronic myelomonocytic
leukemia and juvenile myelomonocytic leukemia].
AB - This study was purposed to explore the therapeutic efficacy and influencing
factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in
patients with chronic myelomonocytic leukemia (CMML) and in patients with
juvenile myelomonocytic leukemia (JMML). The clinical data of 3 cases of CMML and
2 cases of JMML underwent allo-HSCT were analysed in term of multiparameter. The
results showed that the hematopoietic stem cells in 5 patients grafted
successfully. One case of JMML died of pulmonary disease, other 4 cases survive
without disease. The analysis found that the disease burden before transplant,
chromosome karyotype, acute GVHD II-IV and poor risk cytogenetics all associated
with the relapse rate and disease-free survival rate of CMML. The low intensity
conditioning regimen was better than myeloablative conditioning regimen. Type of
donor and source of stem cells did not statistically and significantly affect OS
and RFS. The splenectomy before allo-HSCT as well as spleen size at time of the
alloHSCT did not influence on posttransplantation outcome of JMML. However, cord
blood HSCT for JMML patients delayed hematologic recovery as compared to that of
bone marrow or peripheral blood HSCT. The age, GVHD, HbF level played an
important role in leukemia replace. It is concluded that the allogeneic
hematopoietic stem cell transplantation is a curative regimen for CMML and JMML,
but there also is a serial problems to be resolved.
PMID- 25130829
TI - [Effects of myeloid antigen expression on hematopoietic reconstitution and
disease prognosis in acute lymphocytic leukemia patients after allogeneic stem
cell transplantation].
AB - This study was aimed to investigate the effects of myeloid antigen expression on
hematopoietic reconstitution and disease prognosis in acute lymphocytic leukemia
patients post-allogeneic stem cell transplantation (allo-HSCT). Clinical data of
20 patients with acute lymphocytic leukemia in Department of Hematology of the
First Affiliated Hospital of Xi'an Jiaotong University from 2008 January to 2014
April were retrospectively analyzed, in which 5 cases were with myeloid antigen
(My(+) ALL), while 15 patients were without myeloid antigen expression (My(-)
ALL). Differences in prognosis and hematopoietic reconstitution post-allo-HSCT
were observed in My(+) ALL and My(-) ALL patients. The results showed that the
poor platelet engraftment in patients with My(+) ALL was found more than that in
My(-)ALL patients. Three My(+) ALL patients experienced skin chronic graft versus
host disease (cGVHD) including local in 2 cases and extensive in one case, and 3
My(-) ALL patients developed grade I-II acute GVHD, while five patients of My(-)
ALL experienced cGVHD including local in 3 cases, extensive in 2 cases. One and
two year overall survival rate of My(+) ALL and My(-) ALL patients was 80% and
85.7%, 53% and 69.8% respectively, one and two year progress-free survival rate
was 53.3% and 54.7%, 26% and 27.4%, respectively. And there was no significant
statistical difference between two groups (P > 0.05). It is concluded that the
myeloid antigen expression may impact the platelet engraftment post
transplantation. There is no significant difference between one and two year
overall survival rate and progress-free survival rate of My(+) ALL and My(-) ALL
patients after allogeneic stem cell transplantation.
PMID- 25130830
TI - [Effect of notch signaling pathway on VEGF promoting rat mesenchymal stem cell
proliferation].
AB - This study was purposed to investigate the effect of Notch signaling pathway on
VEGF promoting the proliferation of rat mesenchymal stem cells (MSC). Rat MSC
were cultured in vitro, and the cells in logarithmic growth phase were used for
experiments. The inhibitor DAPT was used to block Notch signaling pathway, and
the effect of the pathway on VEGF promoting proliferation of MSC was observed.
The experiment was divided into 4 groups: control, VEGF, DAPT and VEGF+DAPT. The
CCK-8 was used to assay the cells proliferation of each group, while RT-PCR was
used to detect the changes of related genes (Notch1, Notch2, Flk-1, Hes-1) at
mRNA levels. The results indicated that the cells survival rate MSC in DAPT group
and VEGF+DAPT group was low in each time point (24 h, 48 h, 72 h), the cell
number decreased, and the cells became rounded. The survival rate of MSC in VEGF
group was the highest; the difference of cell survival rate was statistically
significant between the groups (P < 0.01); Compared with the control group, the
mRNA expression level of Notch1, Notch2 and Flk-1 in VEGF group was raised, while
the expression level of Notch1 and Notch2 in DAPT group and VEGF+DAPT group come
down, with statistically significant differences (P < 0.05); whereas the mRNA
expression level of Hes-1 in VEGF group was down-regulated, but that in DAPT
group and VEGF+DAPT group was up-regulated, and the difference was statistically
significant (P < 0.05). Flk-1 mRNA level in DAPT group and VEGF+DAPT group was
slightly lower, but the difference was not statistically significant (P > 0.05).
It is concluded that Notch signaling pathway plays an important role in promoting
the proliferation of rat MSC, treated with VEGF, however, the DAPT can weaken
this effect.
PMID- 25130831
TI - [Effects of salidroside on proliferation of bone marrow mesenchymal stem cells].
AB - This study was aimed to investigate the effect of salidroside on proliferation of
bone marrow mesenchymal stem cells (MSC) and their secretion of stem cell factor
(SCF). MSC were isolated and amplified in vitro via density gradient
centrifugation and adherence screening method. MCS were identified by flow
cytometry and osteogenic/adipogenic induction. The effects of salidroside on cell
proliferation, cell cycle and the SCF secretion of MSC were detected by flow
cytometry. The results showed that the salidroside could induce the proliferation
of MSC, peaked at the concentration of 1.5 mg/ml and in a time-dependent manner
(in 24 h, 48 h and 72 h). Salidroside at 1.5 mg/ml could more effectively
increase the percentage of cells in S and G1/M phase. Co-cultured with
salidroside at the concentration of 1.5 mg/ml for 48 h, the SCF and the
expression levels of SCF mRNA in co-culture supernatant were both significantly
increased (P < 0.01). It is concluded that salidroside in a range of certain
concentration can obviously promote the proliferation of MSC and increase the
expression and secretion of SCF.
PMID- 25130832
TI - [Protective effect of bone marrow mesenchymal stem cell-derived microvesicles on
glutamate injured PC12 cells].
AB - This study was aimed to investigate the protective effect of bone mesenchymal
stem cell-derived microvesicles (BMMSC-MV) on glutamate injured PC12 cells so as
to elucidate the mechanism of the neural damage repair. BMMSC were isolated and
purified with density-gradient centrifugation method, BMMSC-MV were harvested
from the supernatants of BMMSC by hypothermal ultracentrifugation method. The
surface markers of BMMSC reacted against different antibodies were detected by
flow cytometry. The morphology features of MV were observed under an electron
microscope. Experiment was divided into three groups, one was a control group,
and the other two were glutamate-injured group and co-culture group of BMMSC-MV
and glutamate-damaged cells respectively. MTT test was used to evaluate the
proliferative status of PC12 cells and the AnnexinV-FITC detecting kit and
Hoechst33342 were used to detect the apoptosis of PC12 cells in different groups.
The results showed that BMMSC isolated from rat bone marrow were highly positive
for CD29, CD44 and negative for CD31, CD34 and CD45. The morphology of MV was
round and the vesicles were homogenous in size. BMMSC-MV exhibited a protective
effect on the excitotoxicity-injured PC12 cells, displaying increase of cell
viability, decrease of Annexin-V/PI staining positive and nuclear condensed
cells. It is concluded that BMMSC-MV can protect PC12 cells from glutamate
induced apoptosis, suggesting that BMMSC-MV may be a potential candidate for
treatment of neurological diseases.This study provides the preliminary
experimental and theoretical evidence for use of BMMSC-MV in treatment of neural
excited damage.
PMID- 25130833
TI - [Effect of umbilical cord MSC infusion on the pulmonary infection in
haploidentical hematopoietic stem cell transplantation].
AB - This study was purposed to investigate the effect of umbilical cord mesenchymal
cells (UC-MSC) infusion on the pulmonary infection in haploidentical
hematopoietic stem cell transplantation (hi-HSCT). The infection of 83 patients
underwent hi-HSCT was detected and analysed, among them 42 patients received
haploidentical hi-HSCT, 41 received hi-HSCT combined with UC-MSC infusion. The
results showed that 31 cases (73.81% +/- 6.78%) were infected by cytomegalovirus
and 21 cases in patients received hi-HSCT experienced pulmonary infections,
including infections of fungal, virus, bacteria, tubercle bacillus, PCP and so
on, the incidence rate was (50 +/- 7.72)%; the infection of cytomegalovirus (CMV)
was found in 31 cases, the incidence rate was (78.05 +/- 6.46)%. In patients
received hi-HSCT combined with UC-MSC, only 15 patients experienced pulmonary
infection, the incidence rate was (36.59 +/- 7.52)%, and the infection of
cytomegalovirus (CMV) was observed in 32 patients, the incidence rate was (78.05
+/- 6.46)%. There was no obvious statistical difference between two groups(P >
0.05). It is concluded that the UC-MSC infusion not increases the infection rate
in hi-HSCT.
PMID- 25130834
TI - [Infection status of HBV, HCV and HIV in voluntary blood donors of Chinese
Nanjing area during 2010-2013].
AB - This study was purposed to understand the infection of HBV, HCV, HIV among the
voluntary blood donors and the epidemic trend in infectious population in Chinese
Nanjing area, and to guide the mobilization and recruitment of blood donors. A
total of 199777 whole blood samples of voluntary blood donors were tested by
ELISA, the nucleic acid technology (NAT) combined detection (HBV-DNA, HCV-RNA,
HIV-RNA) was added for detection of the samples with HBsAg,anti-HCV, anti-HIV at
least unilateral negative donors from June 10, 2010 to June 9, 2013 years, and
these statistic data were analyzed. Every HIV reactive sample(HIV-antibody and/or
HIV-RNA) was sent to be confirmed in the Centers for Disease Control and
Prevention in Nanjing. The results showed that the voluntary donors' infection
rate of HBsAg, anti-HCV, anti-HIV were 0.45%, 0.28%, 0.11% respectively; NAT
positive rate was 0.07%, 32 cases were confirmed with anti-HIV positive, in which
30 cases were male (6 cases were repeated blood donors) and 2 cases were female,
3 cases were unconfirmed, in which 2 cases were males and 1 case was female. The
statistical analysis demonstrated that the difference of unqualitative rate of
HBsAg, anti-HCV, anti-HIV was statistically significant between the first-time
and repeated blood donors.It is concluded that the positive rate of anti-HCV and
anti-HIV displayed a declining trend year by year in Nanjing voluntary blood
donation population from June 10,2010 to June 9, 2013 years. The unqualitative
rate of HBsAg and NAT increased with the age increasing, while that of anti-HCV,
anti-HIV decreased with age increasing. The unqualitative rate of the repeated
blood donors is far lower than that of the first-time blood donors. The ELISA
positive rate of anti-HIV testing in females is higher than that in males, but
the confirmed positive rate of male is significantly higher than that of female.
Therefore the consulting skills before donating should be improved, concerning
the link of recruiting donors, focusing on strengthening the first-time donors'
consultation, evaluating and developing the fixed voluntary blood donors, and
vigorously popularizing NAT technology in blood screening to improve the blood
safety effectively.
PMID- 25130836
TI - [Holstein-Friesian RBC as human blood substitute].
AB - alpha-Gal, the main xenotransplantation antigen, can lead to hyperacute rejection
(HAR) in xenotransplantation. This study was purposed to investigate the effect
of recombinant alpha-galactosidase (alpha-Gal antigen) on the Holstein-Friesian(H
F) red blood cells (RBC). The enzymelysis method was used to digest the alpha-Gal
antigen on H-F RBC; the saline and anti-human globulin methods were used to
perform the agglutination test of H-F RBC and human plasma; the flow cytometry
was used to detect the alpha-Gal antigen on surface of H-F RBC, fluorescence
intensity of FITC-IB4 and FITC-IgG labeled RBC. The results indicated that the
saline and anti-human globulin method showed alpha-galactosidase-treated H-F RBC
fail to agglutinate with human pooled plasma; the flow cytometry showed the
fluorescence intensity of FITC-IB4 and FITC-IgG labeled RBC decrease 99.0% and
87.8%, respectively. It is concluded that the novel alpha-galactosidase can be
used to cleared the alpha-Gal antigen on the surface of H-F RBC and alpha
galactosidase-treated H-F RBC may be considered as human blood substitute.
PMID- 25130835
TI - [Clinical application of blood matching with hemolytic test in vitro for
transfusion treatment of crisis puerpera with acute hemolytic anemia].
AB - This study was aimed to establish the matching method of hemolytic test in vitro,
and to guide the transfusion treatment for puerpera with acute hemolytic disease.
The donor's erythrocytes were sensibilized by all the antibodies in plasma of
patient in vitro and were added with complement, after incubation for 6.5 hours
at 38 degrees C, the hemolysis or no hemolysis were observed. It is safe to
transfuse if the hemolysis did not occur. The results showed that when the
matching difficulty happened to puerpera with acute hemolytic disease, the
compatible donor could be screened by hemolytic test in vitro. There were no
untoward effects after transfusion of 6 U leukocyte-depleted erythrocyte
suspension. The all hemoglobin, total bilirubins, indirect bilirubin,
reticulocyte, D-dimex and so on were rapidly improved in patient after
transfusion , showing obvious clinical efficacy of treatment. It is concluded
that when the matching results can not judge accurately compatible or
incompatible through the routine method of cross matching, the agglutinated and
no-hemolytic erythrocytes can be screened by hemolytic test in vitro and can be
transfused with good efficacy; the hemoglobin level can be promoted rapidly, and
no untoward effects occur.
PMID- 25130837
TI - [Comparative analysis of collecting mononuclear cells from peripheral blood by
using Fenwal CS-3000 plus, haemonetics MCS plus and COBE spectra separators].
AB - This study was aimed to compare the collection efficiency of mononuclear cells
(MNC) from peripheral blood as well as the changes of blood-related indices in
patient by using 3 cell separators. MNC were collected from 94 tumor patients by
using Fenwal CS-3000plus, Haemonetics MCSplus and COBE spectra separators.
Routine blood test was performed before and after MNC collection to detect the
potential effects of cell separators on blood-related indices in the patients.
MNC count was performed. The percentages of CD3(+), CD4(+) and CD8(+) in
peripheral blood cells were determined. The results showed that the MNC counts
were (3.08 +/- 0.79)*10(9), (3.21 +/- 1.12)*10(9), and (3.22 +/- 1.84)*10(9) per
bag by CS-3000plus, MCSplus and COBE spectra, respectively. And the corresponding
decrease of platelet percentage was (6.86 +/- 5.70)%, (8.05 +/- 5.14)% and (5.89
+/- 4.48)%, respectively. The CD3, CD4 and CD8 ratios in peripheral blood of
patients before and after treatment were significantly statistical different (P <
0.001). It is concluded that the MNC collection can be performed successfully
with CS-3000plus, MCSplus and COBE spectra, and their collections can meet the
needs in clinic.
PMID- 25130838
TI - [Analysis of clinical, iconographical and pathological characteristics, prognosis
and treatment methods for 35 cases of Langerhans cell histiocytosis].
AB - Purpose of this study was to analyse the characteristics of clinical,
iconographical, pathological and treatment methods of Langerhans cell
histiocytosis (LCH), so as to improve the diagnosis and treatment level of this
disease. The clinical data of 35 LCH patients were studied retrospectively. These
patients were divided into 2 groups according to age <14 years old and >= 14
years old. The clinical symptoms were analysed and the signs, imageology and
pathology manifestation and treatment results were evaluated. The results showed
that LCH clinical manifestations were diverse and complex. Surgical treatment for
patients with single system involvement of LCH was better than that of multi
system involvement of LCH (MS-LCH). For the latter, combined chemotherapy effects
was better. After 3-year follow-up, 1-year OS was 94% +/- 4%, 2-years OS was 91%
+/- 5%, 3-year OS was 86% +/- 7%. 3 years OS of group <14 years old and >= 14
years old was 94% +/- 6% and 81% +/- 10% respectively. The OS of former was
better than that of the later, but because a small number of cases, this
difference was not statistically significant. It is concluded that LCH is easy to
be misdiagnosed, the pathological biopsy is the gold standard of LCH diagnosis.
The PET-CT can be of great help in identifying stages and finding lesion areas of
the disease. Pulmonary Langerhans cell histiocytosis (PLCH) is more common in
adult. Combined chemotherapy can improve the prognosis of the patients. The
treatment methods should be choosed according to the stage and classification of
disease.
PMID- 25130839
TI - [Effect of different irradiation doses on the establishment of murine cGVHD model
after MHC matched spleen stem cell transplantation].
AB - This study was aimed to investigate the effect of different irradiation doses on
the establishment of murine cGVHD model after MHC matched spleen stem cell
transplantation. The male mouse BALB/c(H)-2d was totally irradiated with
different radiation dose of (60)Co (TBI), then was infused with the same number
of splenocytes from MHC matched DBA/2 male mice. After transplantation, the
bodyweight, general appearance, hair changes, survival time and pathological
damage were observed. The results indicated that compared to the control group (0
Gy) and the 7.0 Gy group, the mice irradiated with 7.5 Gy and 8.0 Gy showed cGVHD
symptoms and obvious pathological damage. At the end of experiments (60 d after
transplantation), all mice irradiated by 7.5 Gy survived while only 60% animals
survived in the 8.0 Gy group. It is concluded that under infusion of 10(8) MHC
matched splenocytes per mouse, 7.5 Gy irradiation is appropriate to efficiently
establish cGVHD model. This study laid an important foundation for further
studying the pathogenesis, biological characteristics, and intervention factors
of cGVHD.
PMID- 25130840
TI - [Leukemia stem cells and their targeted clearance].
AB - Leukemia stem cells(LSC) are the root causes of the leukemia, and are also the
main reason for the leukemia relapse. Researchers hope that there are some
methods to specifically mark the LSC and to clear them for promoting the
advancements in the treatment of leukemia. This review discusses the biological
characteristics of LSC and its microenvironment, the current internationally
recognized main methods for specific marking of LSC, including marking LSC self
renewal, apoptosis signaling pathways, microenvironment, cell cycle-related
signaling pathways and LSC-specific immune phenotype, so as to eliminate LSC and
minimal residual disease through these marking ways. But, at present, there are
no specific methods to remove leukaemia stem cells independently, possibly the
combination of LSC immune phenotype with blocking the microenvironment signaling
pathways can target at and remove LSC, thus improving the prognosis of leukemia.
PMID- 25130841
TI - [Mechanisms of aging and programmed death of erythrocytes].
AB - Erythrocytes lack nuclei and mitochondria, critical elements in the machinery of
nucleated cell apoptosis. However, most recently, it became obvious that
erythrocytes may undergo programmed aging, as well as suicidal death. The term
eryptosis has been coined to describe the suicidal erythrocyte death. Eryptosis
is triggered mainly by increased cytosolic Ca(2+) activity, in turn, Ca(2+)
activates Ca(2+)-sensitive K(+) channels, scramblase, calpain and other
proteases, respectively. A series of molecular events of erythrocyte programmed
death induced. The cascade reaction of related molecules and finally lead to cell
clearance. There is evidence suggesting that erythrocytes aging and death process
are regulated tightly and there are many molecular participants and signaling
pathways involved in aging and death process of erythrocytes. Erythrocytes have
already been used as a model for aging study, and the knowledge about mechanisms
involved in eryptosis may provide an important clue to understand the mechanisms
involved in suicidal death of nucleated cells. In this review the factors
influencing programmed death of erythrocytes, the role of Ca(2+) and ceramide in
programmed death of erythrocytes, the role of blebbing in process of erythrocyte
aging, the antigens of erythrocyte aging and so on are summarized.
PMID- 25130842
TI - [Autophagy and hematologic malignancies].
AB - Autophagy is a major topic of discussion in recent years, and is a physiological
process of eukaryotic cells under metabolic stress as hunger, hypoxia, and drug
treatment to gain energy by its degradation, and is closely related to the
pathogenesis and progression of hematologic malignancies. At present, the results
of study on the relationship between autophagy and hematologic malignancies has
been found to be indistinct and contradictory. The appropriate treatment should
inhibit the growth of tumor cells selectively and meanwhile have no damage to
normal cells. So how to choose the target strategies plays an important role in
the autophagy related treatment for hematologic malignancies. This article
summarizes the occurrence and development of autophagy, the relationship between
autophagy and hematologic malignancies, as well as the possible mechanism of
autophagy in hematologic malignancies.
PMID- 25130843
TI - [Roles of osteoblasts in hematopoietic stem cell niche and relationship between
osteoblasts and hematopoietic diseases].
AB - Hemopoietic stem cells(HSCs) are regulated by two niches: osteoblastic niche and
vascular niche. Osteoblasts are the critical constitutive regulators of the
osteoblastic niche. The significance of osteoblasts for hematopoietic disease has
not escaped attention. This review attempts to capture the discoveries of the
last few years regarding the role of osteoblasts in hematopoietic stem cell niche
and relationship between osteoblasts and hematopoietic diseases.
PMID- 25130844
TI - [Clinical translational research of chimeric antigen receptor-T (CAR-T) cells for
the treatment of relapsed and refractory B-cell lymphoma/leukemia].
AB - B-cell lymphoma and leukemia are the most common subtypes of malignant lymphomas.
Relapse and refractory to multiple therapy are the main reasons of treatment
failure. As the classical anti-tumor methods, surgery, radiation, chemotherapy
and palliative therapy have cured lots of cancer patients. However, each year
many patients still died of different kinds of hard-to-treat cancers. Although
the ratio of complete remission of B-cell lymphoma/leukemia patients particularly
with CD20 positive mature B cell malignancies has been largely increased after
the application of Rituximab in clinic, nearly 20%-40% patients still died due to
relapse and refractory to the treatment. During last five years, the development
of chimeric antigen receptor-T (CAR-T) cells, especially CD19 CAR-T cells, which
can recognize CD19 specifically expressed on B cells and have been demonstrated
to be significantly effective to relapsed and refractory B cell lymphoma/leukemia
in clinical trials, has gradually attracted extensively concerning from
researchers and clinicians. Many medical institutions all over the world (besides
in China) have registered the clinical trials for B-cell lymphoma/leukemia
patients by use of CAR-T cells. In this review, we summarize the developmental
history, the main ongoing clinical trials and proved potential adverse affects of
CD19 CAR-T cells for the treatment of patients with B-cell lymphoma/leukemia.
PMID- 25130846
TI - [Dendritic cells and acute myeloid leukemia].
AB - Dendritic cells can be derived from leukemia cells and normal precursor cells in
the patients with acute myeloid leukemia (AML). Dendritic cells may capture
leukemia antigen in bone marrow or lymph nodes, and present leukemia common
antigen to stimulate proliferation of specific CD8(+) T cells, playing anti
leukemia effect. Dendritic cells for clinical and experimental use are
transformed from leukemia cells and peripheral blood mononuclear cells and loaded
in vitro with leukemia -specific or tumor common antigen, play a therapeutic role
after reinfusion. This article reviews dendritic cells in the immunotherapy of
AML.
PMID- 25130847
TI - [Research advances on microchimerism].
AB - The microchimerism is a status of the microcell or DNA of an individual in
another one with genetic differences. Taking an overall view about the discovery
and research of the microchimerism, it was found that although the study of the
microchimerism emphasizes the formation, origin, distribution, type, relationship
to disease and several other aspects, the objects of the study are always the
microchimerism that obtained naturally. As it is known to all, the microchimerism
can also be produced in some clinical treatment, such as in the transplant and
transfusion, but compared with the microchimerism gained naturally, obviously,
the study for the iatrogenic microchimerism formed in the treatment is not
elaborate enough. The curative effect of micro transplantation, a new technique
for leukemia treatment, is obvious, but its mechanism is unclear, whether that is
related to microchimerism still needs further research. This review summarizes
the study history and perspective of the microchimerism so as to provide some
ideas for studying the action mechanism of microchimerism in micro
transplantation.
PMID- 25130845
TI - [Research advances on ADAM28 expression and ADAM28-mediated tumor metastasis].
AB - A disintegrin-metalloproteinase 28 (ADAM28) is one of important members of ADAM
family, that is involved in various biological events including cell adhesion,
proteolysis, growth and metastasis of solid tumors and hematological
malignancies. Studies have shown that ADAM28 is highly expressed in several human
tumors, such as lung, breast and bladder cancers, and chronic lymphocytic
leukemia, and its tissue expression levels correlate with cancer metastasis.
ADAM28-mediated cancer cell metastasis may be related with the cleavage of von
Willebrand's factor (vWF), insulin-like growth factor binding protein-3 (IGFBP-3)
and connective tissue growth factor (CTGF), as well as the promoting PSGL-1/P
selectin-mediated cell adhesion. This review summarizes the basic and
translational aspects of ADAM28 biology that might stimulate the interest in
ADAM28 research and discovery of novel ADAM28 targets, providing potential novel
therapies for metastatic cancers.
PMID- 25130848
TI - [Structure and function of ADAMTS13 protease and its relation with diagnosis and
treatment of TTP].
AB - ADAMTS13, a plasma metalloprotease, specifically cleaves von Willebrand factor
(vWF). Severe deficiency of plasma ADAMTS13 activity results in thrombotic
thrombocytopenic purpura (TTP). In this review, the structure and function of
ADAMTS13 protease and its relationship with TTP are summarized.
PMID- 25130849
TI - [Research advances in the pathogenesis, diagnosis and treatment of hemophagocytic
lymphohistiocytosis in children].
AB - Hemophagocytic lymphohistiocytosis (HLH), or hemophagocytic syndrome (HPS), is
characterized clinically by abrupt onset and progressive deterioration and even
death. HLH is much more prevalent in children, and is potentially fatal if early
diagnosis is not made and appropriate HLH-directed therapy not instituted.
Increasing genetic defects and underlying diseases or causative factors have been
identified to be closely implicated in the pathogenesis of HLH. In addition,
great advances have been made in the past few years in terms of HLH diagnosis and
clinical management. In the present review, the cause of disease, contemporary
classification, epidemiology, genetic defects and molecular mechanisms, updated
diagnostic criteria and novel treatment strategies for childhood HLH are
summarized.
PMID- 25130850
TI - [Research advances on roles of ADAMTS-13 in thrombotic diseases].
AB - ADAMTS-13 is a plasma metalloprotease that cleaves von willebrand factor (vWF).At
the present,it has been made great progresses on its structure, biological
characteristics and function. ADAMTS-13 plays an important role in artery and
venous thrombosis,besides controlling the cleaving of vWF, and the activity of
the ADAMTS-13 can be effected by ion concentration and thrombin signal
transduction pathway,but how the mechanism of ADAMTS-13 controlled is still not
clear. This article reviews ADAMTS-13 changes,relevant mechanism and influencing
factors of the enzyme regulation.
PMID- 25130851
TI - [Progress of improving blood donor screening by nucleic acid technology].
AB - With increasing application of blood transfusion, the research of side-effects
such as transfusion-transmitted infections (TTIs) became more and more important.
Up to the 90's of the 20th century, the first blood donor screening for pathogens
transfected from blood transfusion entirely depended on serological test. At this
time, the detection of virus were performed mainly by using method of detecting
antibody, except hepatitis B virus (HBV) can be detected by hepatitis B surface
antigen (HBsAg). Now, the molecular technologies, such as the polymerase chain
reaction (PCR), have been used in clinic. These technologic methods can provide
capability of detection for blood donor screening and reduced possibility of
infection from blood transfusion. This review summarises the development of
nucleic acid amplification technology and describes its current state.
PMID- 25130852
TI - [Recent advances on the prognostic value of immunophenotyping in multiple myeloma
by flow cytometry].
AB - Clinical application of flow cytometry in multiple myeloma (MM) can be found in
various dimensions, such as in differential diagnosis of malignant plasma cell
disorder from reactive plasmacytosis, identification of the progression risk in
MM, and in the detection of minimal residual disease. Flow cytometry-based
clonality assessment with immuno-phenotyping encourages and enables the most
stringent method of diagnosis and follow-up. The objective of this review is to
summarize the recent information of the malignant plasma cell phenotypic profile
of MM. The most comprehensive antigens, such as CD19, CD27, CD28, CD45, CD56 and
CD117, play a significant role in the characterization of normal and malignant
plasma cells. This review also focuses on the association of malignant phenotypic
markers with chromosomal aberrations that identify the specific prognostic
factors in MM.
PMID- 25130853
TI - [Role of ASXL1 mutation in myeloid malignancies].
AB - Additional sex comb-like 1 ( ASXL1) is an enhancer of Trithorax and Polycomb
family, which are necessary for the maintenance of stable repression of homeotic
and other loci. Recently, alterations of ASXL1 gene were identified in the
hematopoietic cells from patients with a variety of myeloid malignancies,
including chronic myelomonocytic leukemia (CMML, 43% of cases), myelodysplastic
syndrome (MDS, 20%), myeloproliferative neoplasms (MPN, 10%) and acute myeloid
leukemia (AML, 20%). The majority of ASXL1 mutations are frameshift and nonsense
mutations. These clinical data suggest an important role of ASXL1 in the
pathogenesis and/or transformation of myeloid malignancies. However, the role of
ASXL1 in the pathogenesis of myeloid malignancies and in normal hematopoiesis in
vivo, as well as the underlying mechanisms remains unknown. This article reviews
the structure and function of ASXL1, the clinical characteristic and prognostic
significance of ASXL1 mutation, the association of ASXL1 with other gene
mutation, as well as ASXL1 knock-down or silence in vitro and in vivo models.
PMID- 25130854
TI - [Research progress on hereditary fibrinogen abnormalities].
AB - As the most abundant component of coagulation system, fibrinogen not only takes
part in clotting, but also works as one of acute phase proteins, which
participates in many physiological and pathophysiological processes. Studies of
fibrinogen abnormalities contribute to understand the molecular basis of
disorders of fibrinogen protein function and metabolism, caused mainly by gene
mutation, commonly associated with bleeding, thrombophilia, or both. Diseases
affecting fibrinogen could be classified to the acquired or inherited disease. In
this review, the research progress on the molecular basis, possible action
mechanism of the hereditary fibrinogen abnormalities and its clinical research
are summarized.
PMID- 25130855
TI - Effect of a novel synthesized sulfonamido-based gallate-SZNTC on chondrocytes
metabolism in vitro.
AB - The ideal therapeutic agent for treatment of osteoarthritis (OA) should have not
only potent anti-inflammatory effect but also favorable biological properties to
restore cartilage function. Gallic acid (GA) and its derivatives are anti
inflammatory agents reported to have an effect on OA (Singh et al., 2003) [1].
However, GA has much weaker antioxidant effects and inferior bioactivity compared
with its derivatives. We modified GA with the introduction of sulfonamide to
synthesize a novel sulfonamido-based gallate named sodium salt of 3,4,5
trihydroxy-N-[4-(thiazol-2-ylsulfamoyl)-phenyl]-benzamide (SZNTC) and analyzed
its chondro-protective and pharmacological effects. Comparison of SZNTC with GA
and sulfathiazole sodium (ST-Na) was also performed. Results showed that SZNTC
could effectively inhibit the Interleukin-1 (IL-1)-mediated induction of
metalloproteinase-1 (MMP-1) and MMP-3 and could induce the expression of tissue
inhibitor of metalloproteinase-1 (TIMP-1), which demonstrated ability to reduce
the progression of OA. SZNTC can also exert chondro-protective effects by
promoting cell proliferation and maintaining the phenotype of articular
chondrocytes, as evidenced by improved cell growth, enhanced synthesis of
cartilage specific markers such as aggrecan, collagen II and Sox9. Expression of
the collagen I gene was effectively down-regulated, revealing the inhibition of
chondrocytes dedifferentiation by SZNTC. Hypertrophy that may lead to chondrocyte
ossification was also undetectable in SZNTC groups. The recommended dose of SZNTC
ranges from 3.91MUg/ml to 15.64MUg/ml, among which the most profound response was
observed with 7.82MUg/ml. In contrast, its source products of GA and ST-Na have a
weak effect in the bioactivity of chondrocytes, which indicated the significance
of this modification. This study revealed SZNTC as a promising novel agent in the
treatment of chondral and osteochondral lesions.
PMID- 25130856
TI - Differential effects of baicalein and its sulfated derivatives in inhibiting
proliferation of human breast cancer MCF-7 cells.
AB - This study was to investigate the anticancer effects of baicalein (Bai) and its
two sulfated derivatives, namely baicalein-7-O-sulfate (BoS) and baicalein-8
sodium sulfonate (BcS). BcS was shown to exhibit stronger growth inhibition
against human breast cancer MCF-7 cells, compared with structurally related Bai
and BoS, where IC50 values of BoS, Bai and BcS were 97.7, 68.3 and 30.4MUM,
respectively. BoS, Bai and BcS were further shown to mediate the cell-cycle
arrest principally in G0/G1-phase within 12h of treatment with MCF-7 cells, and
after 12h, they arrested principally in S-phase. It was also found that 17.7%,
44.9% and 70.5% of MCF-7 cells entered the early phase of apoptosis when treated
with 200MUM BoS, Bai and BcS for 24h, followed by an intracellular ROS
generation. BcS displays strong antitumor effect through ROS-dependent apoptosis
pathway in MCF-7 cells, and has promising potential to be developed as an
antitumor compound.
PMID- 25130857
TI - Carbohydrate malabsorption mechanism for tumor formation in rats treated with the
SGLT2 inhibitor canagliflozin.
AB - Canagliflozin is an SGLT2 inhibitor used for the treatment of type 2 diabetes
mellitus. Studies were conducted to investigate the mechanism responsible for
renal tubular tumors and pheochromocytomas observed at the high dose in a 2-year
carcinogenicity study in rats. At the high dose (100mg/kg) in rats, canagliflozin
caused carbohydrate malabsorption evidenced by inhibition of intestinal glucose
uptake, decreased intestinal pH and increased urinary calcium excretion. In a 6
month mechanistic study utilization of a glucose-free diet prevented carbohydrate
malabsorption and its sequelae, including increased calcium absorption and
urinary calcium excretion, and hyperostosis. Cell proliferation in the kidney and
adrenal medulla was increased in rats maintained on standard diet and
administered canagliflozin (100mg/kg), and in addition an increase in the renal
injury biomarker KIM-1 was observed. Increased cell proliferation is considered
as a proximal event in carcinogenesis. Effects on cell proliferation, KIM-1 and
calcium excretion were inhibited in rats maintained on the glucose-free diet,
indicating they are secondary to carbohydrate malabsorption and are not direct
effects of canagliflozin.
PMID- 25130858
TI - Role of Rho small GTPases in meniscus cells.
AB - We previously reported that mechanical stretch regulates Sry-type HMG box (SOX) 9
dependent alpha1(II) collagen (COL2A1) expression in inner meniscus cells. This
study examined the role of the small Rho guanosine 5' triphosphatase Rac1 and Rho
associated kinase (ROCK) in the regulation of stretch-induced SOX9 gene
expression in cultured human inner meniscus cells. COL2A1 and SOX9 gene
expression was assessed by real-time PCR after application of uni-axial cyclic
tensile strain (CTS) in the presence or absence of ROCK and Rac1 inhibitors. The
subcellular localization of SOX9 and the Rac1 effector cyclic AMP response
element-binding protein (CREB), the phosphorylation state of SOX9, Rac1
activation, and the binding of CREB to the SOX9 promoter were assessed. CTS
increased the expression of COL2A1 and SOX9, which was suppressed by inhibition
of Rac1. ROCK inhibition enhanced COL2A1 and SOX9 gene expression in the absence
of CTS. CTS stimulated the nuclear translocation and phosphorylation of SOX9, and
increased Rac1 activation. CTS also increased the binding of CREB to the SOX9
promoter. The results suggest that mechanical stretch-dependent upregulation of
SOX9 by CREB in inner meniscus cells depends on the antagonistic activities of
ROCK and Rac1.
PMID- 25130860
TI - Activated recombinant factor VIIa should not be used in patients with refractory
variceal bleeding: it is mostly ineffective, is expensive, and may rarely cause
serious adverse events.
PMID- 25130859
TI - Nutritional assessment of amyotrophic lateral sclerosis in routine practice:
value of weighing and bioelectrical impedance analysis.
AB - INTRODUCTION: We evaluated clinical and bioelectrical impedance (BIA) parameters
at the time of diagnosis and during follow-up and associated these parameters
with survival in amyotrophic lateral sclerosis (ALS) patients. METHODS: One
hundred seventeen patients were enrolled and were evaluated prospectively every 3
months. All patients underwent at least 1 BIA-based assessment, and 73 underwent
at least 2 assessments. Data regarding the site of onset, age at onset, weight,
body mass index (BMI), amyotrophic lateral sclerosis functional rating scale
score (ALSFRS), fat-free mass (FFM), fat mass (FM), and phase angle (PA) were
collected. RESULTS: At the time of diagnosis, weight loss exceeding 5% of the
premorbid weight and low PA were poor prognostic factors. During follow-up, a
decrease of PA and FFM were associated with shorter survival, regardless of
weight loss. CONCLUSIONS: These results confirm that BIA is useful to identify
poor prognostic factors at the time of diagnosis and during follow-up and thus
could be used to monitor patients during follow-up. Early identification of poor
prognostic factors enables nutritional management and might improve patient
survival.
PMID- 25130861
TI - Surgical extrusion of multiple teeth with crown-root fractures: a case report
with 18-months follow up.
AB - The objective of this case report is to describe the treatment procedure involved
in surgical extrusion of multiple crown-root fractures and review the critical
factors to be considered for successful and predictable outcome. The treatment of
complicated crown-root fracture in anterior teeth is likely to compromise
function and aesthetics when approached with conventional surgical crown
lengthening. Orthodontic extrusion has also been suggested; however, it is time
consuming, aesthetically compromising and hardly applicable on multiple anterior
crown-root fractures due to the limited source of anchorage. To overcome the
shortcomings of suggested treatment modalities, we performed atraumatic surgical
extrusion of four anterior fractured teeth along with their rotation within the
sockets. The teeth were gently luxated and extruded to the desired position,
minimizing damage to the marginal alveolar bone and root surfaces without rigid
splint. The treated teeth were functioning normally 18 months after the
procedure, and the mobility and probing depths were within normal limits.
Radiographs revealed functional periodontal ligament space along with lamina dura
formation around the extruded roots. There was neither root resorption nor
significant marginal bone loss. This technique might be a promising alternative
to conventional crown lengthening, especially in the anterior zone to avoid
functional or aesthetic complications.
PMID- 25130863
TI - Relationships between dietary intakes of children and their parents: a cross
sectional, secondary analysis of families participating in the Family Diet
Quality Study.
AB - BACKGROUND: Being overweight and obese in Australian children is common. Current
evidence related to parental influence on child dietary intake is conflicting,
and is particularly limited in terms of which parent exerts the stronger
relationship. The present study aimed to assess mother-father and parent-child
dietary relationships and to identify which parent-child relationship is
stronger. METHODS: A cross-sectional analysis was performed of dietary intake
data from 66 families with one parent and one child aged 8-12 years who were
participating in the Family Diet Quality Study, in the Hunter and Forster regions
of New South Wales, Australia. Dietary intakes were assessed using adult and
child specific, validated semi-quantitative 120-item food frequency
questionnaires. Diet quality and variety subscores were assessed using the
Australian Recommended Food Scores for adults and children/adolescents. Pearson's
correlations were used to assess dietary relationships between mother-father,
father-child and mother-child dyads. RESULTS: Weak-to-moderate correlations were
found between mother-child dyads for components of dietary intake (r = 0.27
0.47). Similarly, for father-child dyads, predominantly weak-to-moderate
correlations were found (r = 0.01-0.52). Variety of fruit intake was the most
strongly correlated in both parent-child dyads, with the weakest relationships
found for fibre (g 1000 kJ(-1) ) in father-child and percentage energy from total
fats for mother-child dyads. Mother-father dyads demonstrated mostly moderate-to
strong correlations (r = 0.13-0.73), with scores for condiments showing the
weakest relationship and vegetables the strongest. For all dyads, strong
correlations were observed for overall diet quality (r = 0.50-0.59). CONCLUSIONS:
Parent-child dietary intake is significantly related but differs for mother
versus fathers. Further research is required to examine whether differing dietary
components should be targeted for mothers versus fathers in interventions aiming
to improve family dietary patterns.
PMID- 25130864
TI - Sono-assisted extraction of alcohol-insoluble extract from Althaea rosea:
purification and chemical analysis.
AB - A Box-Behnken design (BBD) was used to evaluate the effects of ultrasonic power,
extraction time, extraction temperature, and water to raw material ratio on
extraction yield of alcohol-insoluble polysaccharide of Althaea rosea leaf
(ARLP). Purification was carried out by dialysis method. Chemical analysis of
ARLP revealed contained 12.69 +/- 0.48% moisture, 79.33 +/- 0.51% total sugar,
3.82 +/- 0.21% protein, 11.25 +/- 0.37% uronic acid and 3.77 +/- 0.15% ash. The
response surface methodology (RSM) showed that the significant quadratic
regression equation with high R(2) (=0.9997) was successfully fitted for
extraction yield of ARLP as function of independent variables. The overall
optimum region was found to be at the combined level of ultrasonic power 91.85 W,
extraction time 29.94 min, extraction temperature 89.78 degrees C, and the ratio
of water to raw material 28.77 (mL/g). At this optimum point, extraction yield of
ARLP was 19.47 +/- 0.41%. No significant (p>0.05) difference was found between
the actual and predicted (19.30 +/- 0.075%) values. The results demonstrated that
ARLP had strong scavenging activities on DPPH and hydroxyl radicals.
PMID- 25130865
TI - Predictors of cerebral microembolization during phased radiofrequency ablation of
atrial fibrillation: role of the ongoing rhythm and the site of energy delivery.
AB - BACKGROUND: Pulmonary vein isolation with phased radiofrequency current and use
of a pulmonary vein ablation catheter (PVAC) has recently been associated with a
high incidence of clinically silent brain infarcts on diffusion-weighted magnetic
resonance imaging, and a high microembolic signal (MES) count detected by
transcranial Doppler. We investigated the potential effects of the ongoing rhythm
and the target vein during energy delivery (ED) on MES generation during PVAC
ablations. METHODS AND RESULTS: A total of 735 EDs during 48 PVAC ablations were
analyzed. MES counts were recorded for each ED and time-stamped for correlation
with the ongoing rhythm and the target vein for each ED. Significantly higher MES
counts were observed during ablations of the left-sided as compared with the
right-sided pulmonary veins (P = 0.0003). Similarly, higher MES counts were
detected during EDs in atrial fibrillation as compared with sinus rhythm when the
temperature was >56 degrees C (P < 0.0001). The ongoing rhythm had no effect on
the number of MESs at lower temperatures during ablation. CONCLUSIONS: Both the
ongoing rhythm during ED and the site of ablation influence microembolus
generation during PVAC ablation procedures.
PMID- 25130862
TI - Predicting the evolution of spreading on complex networks.
AB - Due to the wide applications, spreading processes on complex networks have been
intensively studied. However, one of the most fundamental problems has not yet
been well addressed: predicting the evolution of spreading based on a given
snapshot of the propagation on networks. With this problem solved, one can
accelerate or slow down the spreading in advance if the predicted propagation
result is narrower or wider than expected. In this paper, we propose an iterative
algorithm to estimate the infection probability of the spreading process and then
apply it to a mean-field approach to predict the spreading coverage. The
validation of the method is performed in both artificial and real networks. The
results show that our method is accurate in both infection probability estimation
and spreading coverage prediction.
PMID- 25130868
TI - Psychopathy and Low Anxiety: Meta-Analytic Evidence for the Absence of
Inhibition, Not Affect.
AB - Despite historical conviction that the psychopath is low-anxious, contemporary
research remains equivocal. An examination of the literature suggests that the
lack of consensus may be due to problems with the conceptualization of
"psychopathic low anxiety." It was hypothesized that ambiguous relations could be
clarified by parsing the psychopathic low anxiety construct into more discrete
components: anxiety, fear, and constraint. The current study examined the
relations between psychopathy and these three different low anxiety
conceptualizations through three meta-analyses. Results indicated that anxiety
and fear were negligibly related to psychopathy Total. In contrast, constraint
demonstrated a medium negative relation with psychopathy Total. Relations showed
divergence across psychopathy factor scores. Anxiety, fear, and constraint were
all negatively related to Factor 1 scores, whereas anxiety was positively
related, and constraint negatively related, to Factor 2 scores. These meta
analytic findings suggest that although psychopathic individuals have deficits in
inhibition/constraint, they do not necessarily exhibit a consistent absence of
negative affect. This interpretation is consistent with predictions regarding the
personality correlates of the factors of psychopathy, indicating that while
constraint composes a large part of psychopathy assessments, it is less clear how
much anxiety lends to the construct.
PMID- 25130866
TI - Prevalence and correlates of treatment failure among Kenyan children hospitalised
with severe community-acquired pneumonia: a prospective study of the clinical
effectiveness of WHO pneumonia case management guidelines.
AB - OBJECTIVE: To determine the extent and pattern of treatment failure (TF) among
children hospitalised with community-acquired pneumonia at a large tertiary
hospital in Kenya. METHODS: We followed up children aged 2-59 months with WHO
defined severe pneumonia (SP) and very severe pneumonia (VSP) for up to 5 days
for TF using two definitions: (i) documentation of pre-defined clinical signs
resulting in change of treatment (ii) primary clinician's decision to change
treatment with or without documentation of the same pre-defined clinical signs.
RESULTS: We enrolled 385 children. The risk of TF varied between 1.8% (95% CI 0.4
5.1) and 12.4% (95% CI 7.9-18.4) for SP and 21.4% (95% CI 15.9-27) and 39.3% (95%
CI 32.5-46.4) for VSP depending on the definition applied. Higher rates were
associated with early changes in therapy by clinician in the absence of an
obvious clinical rationale. Non-adherence to treatment guidelines was observed
for 70/169 (41.4%) and 67/201 (33.3%) of children with SP and VSP, respectively.
Among children with SP, adherence to treatment guidelines was associated with the
presence of wheeze on initial assessment (P = 0.02), while clinician non
adherence to guideline-recommended treatments for VSP tended to occur in children
with altered consciousness (P < 0.001). Using propensity score matching to
account for imbalance in the distribution of baseline clinical characteristics
among children with VSP revealed no difference in TF between those treated with
the guideline-recommended regimen vs. more costly broad-spectrum alternatives
[risk difference 0.37 (95% CI -0.84 to 0.51)]. CONCLUSION: Before revising
current pneumonia case management guidelines, standardised definitions of TF and
appropriate studies of treatment effectiveness of alternative regimens are
required.
PMID- 25130867
TI - Mutation in the nuclear-encoded mitochondrial isoleucyl-tRNA synthetase IARS2 in
patients with cataracts, growth hormone deficiency with short stature, partial
sensorineural deafness, and peripheral neuropathy or with Leigh syndrome.
AB - Mutations in the nuclear-encoded mitochondrial aminoacyl-tRNA synthetases are
associated with a range of clinical phenotypes. Here, we report a novel disorder
in three adult patients with a phenotype including cataracts, short-stature
secondary to growth hormone deficiency, sensorineural hearing deficit, peripheral
sensory neuropathy, and skeletal dysplasia. Using SNP genotyping and whole-exome
sequencing, we identified a single likely causal variant, a missense mutation in
a conserved residue of the nuclear gene IARS2, encoding mitochondrial isoleucyl
tRNA synthetase. The mutation is homozygous in the affected patients,
heterozygous in carriers, and absent in control chromosomes. IARS2 protein level
was reduced in skin cells cultured from one of the patients, consistent with a
pathogenic effect of the mutation. Compound heterozygous mutations in IARS2 were
independently identified in a previously unreported patient with a more severe
mitochondrial phenotype diagnosed as Leigh syndrome. This is the first report of
clinical findings associated with IARS2 mutations.
PMID- 25130869
TI - Wasted, overdosed, or beyond saving--to act or not to act? Heroin users' views,
assessments, and responses to witnessed overdoses in Malmo, Sweden.
AB - BACKGROUND: Overdose is a significant cause of death among heroin users.
Frequently, other heroin users are present when an overdose occurs, which means
the victim's life could be saved. There is a lack of studies that, based on
heroin users own stories, examine their views, assessments, and responses to
witnessed overdoses. METHODS: The study is based on qualitative interviews with
thirty-five heroin users who witnessed someone else's overdose. RESULTS: The
heroin users generally had a positive attitude towards assisting peers who had
overdosed. A number of factors and circumstances, however, contribute to
witnesses often experiencing resistance to or ambivalence about responding. The
witness's own high, the difficulty in assessing the seriousness of the situation,
an unwillingness to disturb someone else's high, uncertainty about the motive
behind the overdose and whether the victim does or does not want assistance as
well as fear of police involvement, were common factors that acted as barriers to
adequate responses in overdose situations. CONCLUSION: The fact that being high
makes it difficult to respond to overdoses, using traditional methods, argues for
simpler and more effective response techniques. This can include intranasal
naloxone programs for heroin users. The findings regarding the uncertainty about
the intention of the overdose victim and the sensitivity to the experience of a
good high argue for more up-front communication and discussion amongst using
peers so that they can make their intentions clear to each other. Issues like
this can be addressed in overdose education interventions. Overdose prevention
measures also need to address the fact that fear of the police acts as a barrier
to call emergency services.
PMID- 25130870
TI - N-heterocyclic carbene catalyzed formal [3+2] annulation reaction of enals: an
efficient enantioselective access to spiro-heterocycles.
AB - A highly enantioselective N-heterocyclic carbene (NHC) catalyzed formal [3+2]
annulation of alpha,beta-unsaturated aldehydes with azaaurones or aurone
generating spiro-heterocycles has been developed. The protocol represents a
unique NHC-activation-based approach to access spiro-heterocyclic derivatives
bearing a quaternary stereogenic center with high optical purity (up to 95% ee).
PMID- 25130872
TI - Structure, stability, and IgE binding of the peach allergen Peamaclein (Pru p 7).
AB - Knowledge of the structural properties of allergenic proteins is a necessary
prerequisite to better understand the molecular bases of their action, and also
to design targeted structural/functional modifications. Peamaclein is a recently
identified 7 kDa peach allergen that has been associated with severe allergic
reactions in sensitive subjects. This protein represents the first component of a
new allergen family, which has no 3D structure available yet. Here, we report the
first experimental data on the 3D-structure of Peamaclein. Almost 75% of the
backbone resonances, including two helical stretches in the N-terminal region,
and four out of six cysteine pairs have been assigned by 2D-NMR using a natural
protein sample. Simulated gastrointestinal digestion experiments have highlighted
that Peamaclein is even more resistant to digestion than the peach major allergen
Pru p 3. Only the heat-denatured protein becomes sensitive to intestinal
proteases. Similar to Pru p 3, Peamaclein keeps its native 3D-structure up to 90
degrees C, but it becomes unfolded at temperatures of 100-120 degrees C. Heat
denaturation affects the immunological properties of both peach allergens, which
lose at least partially their IgE-binding epitopes. In conclusion, the data
collected in this study provide a first set of information on the molecular
properties of Peamaclein. Future studies could lead to the possible use of the
denatured form of this protein as a vaccine, and of the inclusion of cooked peach
in the diet of subjects allergic to Peamaclein.
PMID- 25130873
TI - Retinoic acid signaling in cancer: The parable of acute promyelocytic leukemia.
AB - Inevitably fatal some 40 years, acute promyelocytic leukemia (APL) can now be
cured in more than 95% of cases. This clinical success story is tightly linked to
tremendous progress in our understanding of retinoic acid (RA) signaling. The
discovery of retinoic acid receptor alpha (RARA) was followed by the cloning of
the chromosomal translocations driving APL, all of which involve RARA. Since
then, new findings on the biology of nuclear receptors have progressively
enlightened the basis for the clinical efficacy of RA in APL. Reciprocally, the
disease offered a range of angles to approach the cellular and molecular
mechanisms of RA action. This virtuous circle contributed to make APL one of the
best-understood cancers from both clinical and biological standpoints. Yet, some
important questions remain unanswered including how lessons learnt from RA
triggered APL cure can help design new therapies for other malignancies.
PMID- 25130871
TI - The chicken model of spontaneous ovarian cancer.
AB - The chicken is a unique experimental model for studying the spontaneous onset and
progression of ovarian cancer (OVC). The prevalence of OVC in chickens can range
from 5 to 35% depending on age, genetic strain, reproductive history, and diet.
Furthermore, the chicken presents epidemiological, morphological, and molecular
traits that are similar to human OVC making it a relevant experimental model for
translation research. Similarities to humans include associated increased risk of
OVC with the number of ovulations, common histopathological subtypes including
high-grade serous, and molecular-level markers or pathways such as CA-125
expression and p53 mutation frequency. Collectively, the similarities between
chicken and human OVC combined with a tightly controlled genetic background and
predictable onset window provides an outstanding experimental model for studying
the early events and progression of spontaneous OVC tumors under controlled
environmental conditions. This review will cover the existing literature on OVC
in the chicken and highlight potential opportunities for further exploitation
(e.g. biomarkers, prevention, treatment, and genomics).
PMID- 25130875
TI - Abstracts of the 70th Congress of the Italian Society of Pediatrics, June 11-14,
2014, Palermo, Italy.
PMID- 25130874
TI - Impact of VEGFA -583C > T polymorphism on serum VEGF levels and the
susceptibility to acute chest syndrome in pediatric patients with sickle cell
disease.
AB - We investigated the association of VEGFA -583C > T on VEGF serum levels and acute
chest syndrome (ACS) in 351 pediatric patients with sickle cell disease (SCD), of
whom 90 had ACS, and 261 were ACS-free controls. Significant differences in -583C
> T minor allele and genotype frequencies were seen between ACS cases and
controls, evidenced by enrichment of -583T/T genotypes in patients with ACS,
which were linked with reduction in VEGF serum levels. VEGFA -583C > T and
reduced VEGF serum levels may influence ACS risk in patients with SCD, which will
aid in identifying patients with SCD who are at high risk of ACS.
PMID- 25130876
TI - Incidence and risk factors of poor mobilization in adult autologous peripheral
blood stem cell transplantation: a single-centre experience.
AB - BACKGROUND AND OBJECTIVES: Collection of sufficient CD34+ cells for autologous
peripheral blood stem cell (PBSC) transplantation is frequently failed in
patients with lymphoma or multiple myeloma (MM). We investigated the incidence
and the predictive factors for poor mobilization. MATERIALS AND METHODS: A total
of 205 adult patients (101 lymphoma and 104 MM) were retrospectively included for
identifying the incidence of mobilization failure and the predictive factors for
poor mobilization in conventional G-CSF-based mobilization regimen. Another 17
patients who used plerixafor for mobilization were included. RESULTS: Overall,
14.1% of patients (21.8% of patients with lymphoma, 6.7% of patients with MM)
were poor mobilizers. Univariate analysis and multivariate analysis revealed an
interval from G-CSF administration to PBSC collection exceeding 10 days and
peripheral blood mononuclear cells count on the first day of collection were
predictive factors for poor mobilization in lymphoma, but not in MM. Among
plerixafor-treated patient group, 9 of 11 poor mobilizers who received second
cycle plerixafor mobilization were able to collect higher number of CD34+ cells
than that of CD34+ cells during the G-CSF-based first mobilization. All patients
who had received initial plerixafor mobilization reached 2.0 * 10(6) CD34+
cells/kg during the four leukaphereses. CONCLUSION: In conventional G-CSF-based
mobilization, early PBSC collection after G-CSF administration might enhance
CD34+ cell yield. A combination of a new mobilizing agent, plerixafor, would be
helpful to harvest sufficient number of CD34+ cells for successful
transplantation outcome while reducing the effort of collection procedures in
poor mobilizers.
PMID- 25130878
TI - Surface charge effects on optical trapping of nanometer-sized lipid vesicles.
AB - Optical trapping of nanometer-sized lipid vesicles has been challenging due to
the low refractive index contrast of the thin lipid bilayer to the aqueous
medium. Using an "optical bottle", a recently developed technique to measure
interactions of nanoparticles trapped by an infrared laser, we report, for the
first time, quantitative measurements of the trapping energy of charged lipid
vesicles. We found that the trapping energy increases with the relative amount of
anionic lipids (DOPG) to neutral lipids (DOPC) in vesicles. Moreover, as
monovalent salt is added into the exterior solution of vesicles, the trapping
energy rapidly approaches zero, and this decrease in trapping energy strongly
depends on the amount of anionic lipids in vesicles. A simple model with our
experimental observations explains that the trapping energy of charged lipid
vesicles is highly correlated with the surface charge density and electric double
layer. In addition, we demonstrated selective trapping of a binary mixture of
vesicles in different mole fractions of charged lipids, a strategy that has
potential implications on charge selective vesicle sorting for engineering
applications.
PMID- 25130879
TI - Biomarker driven population enrichment for adaptive oncology trials with time to
event endpoints.
AB - The development of molecularly targeted therapies for certain types of cancers
has led to the consideration of population enrichment designs that explicitly
factor in the possibility that the experimental compound might differentially
benefit different biomarker subgroups. In such designs, enrollment would
initially be open to a broad patient population with the option to restrict
future enrollment, following an interim analysis, to only those biomarker
subgroups that appeared to be benefiting from the experimental therapy. While
this strategy could greatly improve the chances of success for the trial, it
poses several statistical and logistical design challenges. Because late-stage
oncology trials are typically event driven, one faces a complex trade-off between
power, sample size, number of events, and study duration. This trade-off is
further compounded by the importance of maintaining statistical independence of
the data before and after the interim analysis and of optimizing the timing of
the interim analysis. This paper presents statistical methodology that ensures
strong control of type 1 error for such population enrichment designs, based on
generalizations of the conditional error rate approach. The special difficulties
encountered with time-to-event endpoints are addressed by our methods. The
crucial role of simulation for guiding the choice of design parameters is
emphasized. Although motivated by oncology, the methods are applicable as well to
population enrichment designs in other therapeutic areas.
PMID- 25130877
TI - Telechelic poly(2-oxazoline)s with a biocidal and a polymerizable terminal as
collagenase inhibiting additive for long-term active antimicrobial dental
materials.
AB - Dental repair materials face the problem that the dentin below the composite
fillings is actively decomposed by secondary caries and extracellular proteases.
To address this problem, poly(2-methyloxazoline) with a biocidal and a
polymerizable terminal was explored as additive for a commercial dental adhesive.
2.5 wt% of the additive rendered the adhesive contact-active against
Streptococcus mutans and washing with water for 101 d did not diminish this
effect. The adhesive with 5 wt% additive kills S. mutans cells in the tubuli of
bovine dentin. Further, the additive inhibits bacterial collagenase at 0.5 wt%
and reduces activity of MMP-9. Human MMPs bound to dentin are inhibited by 96% in
a medium with 5 wt% additive. Moreover, no adverse effect on the enamel/dentine
shear bond strength was detected.
PMID- 25130880
TI - Glutathione S-transferase Mu-1 gene polymorphism in Egyptian patients with
idiopathic male infertility.
AB - The aim of this study was to examine whether an association exists between
glutathione S-transferase Mu-1 (GSTM1) gene polymorphism and idiopathic male
infertility. Sixty men with primary idiopathic infertility and 60 fertile men,
serving as controls, were recruited for the study. The polymorphism was analysed
using polymerase chain reaction-restriction fragment length polymorphism (PCR
RFLP) technique. The frequency of GSTM1 null genotype was observed to be higher
in infertile men 40% in comparison with 33.3% in the fertile men, but this
difference was not statistically significant. There was statistically significant
difference between cases and controls as regards GSTM1 genotype distribution
((MC) P = 0.006*) in GSTM1-positive men. Patients with the GSTM1 null genotype
had significantly lower sperm concentrations and total sperm count when compared
with patients with GSTM1-positive genotype. In the control group, men with GSTM1
null genotype had significantly lower sperm concentrations but not total sperm
count when compared with men with GSTM1-positive genotype. The results of this
study suggest a possible negative effect of GSTM1 null genotype on the
spermatogenic potential of the testis.
PMID- 25130881
TI - Microbial existence in controlled habitats and their resistance to space
conditions.
AB - The National Research Council (NRC) has recently recognized the International
Space Station (ISS) as uniquely suitable for furthering the study of microbial
species in closed habitats. Answering the NRC's call for the study, in
particular, of uncommon microbial species in the ISS, and/or of those that have
significantly increased or decreased in number, space microbiologists have begun
capitalizing on the maturity, speed, and cost-effectiveness of molecular/genomic
microbiological technologies to elucidate changes in microbial populations in the
ISS and other closed habitats. Since investigators can only collect samples
infrequently from the ISS itself due to logistical reasons, Earth analogs, such
as spacecraft-assembly clean rooms, are used and extensively characterized for
the presence of microbes. Microbiologists identify the predominant, problematic,
and extremophilic microbial species in these closed habitats and use the ISS as a
testbed to study their resistance to extreme extraterrestrial environmental
conditions. Investigators monitor the microbes exposed to the real space
conditions in order to track their genomic changes in response to the selective
pressures present in outer space (external to the ISS) and the spaceflight (in
the interior of the ISS). In this review, we discussed the presence of microbes
in space research-related closed habitats and the resistance of some microbial
species to the extreme environmental conditions of space.
PMID- 25130882
TI - Promoting effects of a single Rhodopseudomonas palustris inoculant on plant
growth by Brassica rapa chinensis under low fertilizer input.
AB - Several Rhodopseudomonas palustris strains have been isolated from rice paddy
fields in Taiwan by combining the Winogradsky column method and molecular marker
detection. These isolates were initially screened by employing seed germination
and seedling vigor assays to evaluate their potential as inoculants. To fulfill
the demand in the present farming system for reducing the application of chemical
fertilizers, we assessed the plant growth-promoting effects of the R. palustris
YSC3, YSC4, and PS3 inoculants on Brassica rapa chinensis (Chinese cabbage)
cultivated under a half quantity of fertilizer. The results obtained showed that
supplementation with approximately 4.0*10(6) CFU g(-1) soil of the PS3 inoculant
at half the amount of fertilizer consistently produced the same plant growth
potential as 100% fertility, and also increased the nitrogen use efficiency of
the applied fertilizer nutrients. Furthermore, we noted that the plant growth
promotion rate elicited by PS3 was markedly higher with old seeds than with new
seeds, suggesting it has the potential to boost the development of seedlings that
were germinated from carry-over seeds of poor quality. These beneficial traits
suggest that the PS3 isolate may serve as a potential PGPR inoculant for
integrated nutrient management in agriculture.
PMID- 25130883
TI - Phylogeny and functions of bacterial communities associated with field-grown rice
shoots.
AB - Metagenomic analysis was applied to bacterial communities associated with the
shoots of two field-grown rice cultivars, Nipponbare and Kasalath. In both
cultivars, shoot microbiomes were dominated by Alphaproteobacteria (51-52%),
Actinobacteria (11-15%), Gammaproteobacteria (9-10%), and Betaproteobacteria (4
10%). Compared with other rice microbiomes (root, rhizosphere, and phyllosphere)
in public databases, the shoot microbiomes harbored abundant genes for C1
compound metabolism and 1-aminocyclopropane-1-carboxylate catabolism, but fewer
genes for indole-3-acetic acid production and nitrogen fixation. Salicylate
hydroxylase was detected in all microbiomes, except the rhizosphere. These
genomic features facilitate understanding of plant-microbe interactions and
biogeochemical metabolism in rice shoots.
PMID- 25130884
TI - Space habitation and microbiology: status and roadmap of space agencies.
PMID- 25130886
TI - Linear-dendritic copolymers/indoxacarb supramolecular systems: biodegradable and
efficient nano-pesticides.
AB - Photodegradable and biocompatible nano-indoxacarb was prepared successfully by
encapsulation of indoxacarb with poly(citric acid)-poly(ethylene glycol)
poly(citric acid) (PCA-PEG-PCA) ABA type linear-dendritic copolymers both with
(nano-IND/TiO2) and without (nano-IND) TiO2 nanoparticles via supramolecular
interactions. Preparation of nano-indoxacarb by both formulae was confirmed using
spectroscopy and microscopy analyses. TEM images showed small particles with
average sizes of 10 nm for nano-IND and 12 nm for nano-IND/TiO2. Interestingly,
the rate of degradation of indoxacarb in both nano-IND/TiO2 and nano-IND exposed
to UV and natural light was higher than that for free indoxacarb in the presence
of TiO2 nanoparticles. Furthermore, results of bioassay experiments on the model
pest showed that the essential dosage of pesticide for pest control significantly
decreased when nano-IND and nano-IND/TiO2 were used. Because of the higher
loading capacity and slower release rate for indoxacarb from nano-IND than from
nano-IND/TiO2, and because TiO2 nanoparticles show toxicity in bioassay
experiments, nano-IND is introduced as a promising and eco-friendly pesticide
system.
PMID- 25130885
TI - Microbial monitoring of crewed habitats in space-current status and future
perspectives.
AB - Previous space research conducted during short-term flight experiments and long
term environmental monitoring on board orbiting space stations suggests that the
relationship between humans and microbes is altered in the crewed habitat in
space. Both human physiology and microbial communities adapt to spaceflight.
Microbial monitoring is critical to crew safety in long-duration space habitation
and the sustained operation of life support systems on space transit vehicles,
space stations, and surface habitats. To address this critical need, space
agencies including NASA (National Aeronautics and Space Administration), ESA
(European Space Agency), and JAXA (Japan Aerospace Exploration Agency) are
working together to develop and implement specific measures to monitor, control,
and counteract biological contamination in closed-environment systems. In this
review, the current status of microbial monitoring conducted in the International
Space Station (ISS) as well as the results of recent microbial spaceflight
experiments have been summarized and future perspectives are discussed.
PMID- 25130887
TI - Pediatric tracheostomy revisited: a nine-year experience using horizontal
intercartilaginous incision.
AB - OBJECTIVES/HYPOTHESIS: To describe our tracheostomy procedure using a vertical
skin incision and a horizontal intercartilaginous incision and to compare our
postoperative results with those in the recent literature. STUDY DESIGN:
Retrospective chart review and literature review. METHODS: One hundred eleven
children underwent tracheostomy using a vertical skin incision and a horizontal
intercartilaginous incision over a 9-year period. A retrospective chart review
was undertaken with respect to the following variables: demographics, weight,
primary diagnosis, surgical indication, follow-up duration, decannulation,
interval between tracheostomy and decannulation, and complications experienced.
In addition, the outcomes were compared to results from a literature review.
RESULTS: Of the 111 patients, 56 had a history of prolonged intubation, 52 had
upper airway obstruction, and three underwent tracheostomy for tracheobronchial
toileting. Three (2.7%) patients experienced early major complications without
major sequelae, and 14 (12.6%) experienced late major complications. Twenty-one
(18.9%) patients were decannulated during the follow-up period, whereas 17
(17.8%) died of their primary disease or tracheostomy-related complications (15
died of their primary disease and two died of tracheostomy-related
complications). The complication rates showed overall no differences, but our
patient series showed significantly less stomal granulation tissue formation and
non-significant trend for less suprastomal collapse as compared with previous
literature. CONCLUSIONS: Pediatric tracheostomy using a vertical skin incision
and horizontal intercartilaginous incision is comparable with the conventional
procedure in terms of complication and mortality rates. Future randomized
controlled studies are mandatory to directly compare conventional tracheotomy
using a vertical skin incision and a horizontal intercartilaginous incision with
our procedure. LEVEL OF EVIDENCE: 4.
PMID- 25130888
TI - Evaluation and management of heart rhythm disturbances due to cardiac
sarcoidosis.
AB - Cardiac sarcoidosis (CS) affects less than 5% of patients with pulmonary or
systemic sarcoidosis, but when present is often associated with a spectrum of
clinically significant conduction abnormalities and arrhythmias. The cardinal
manifestations of CS include conduction disturbances, arrhythmias, or congestive
heart failure. Less commonly, there is concealed subclinical disease. The
electrophysiologic evaluation for CS includes a history and physical exam, ECG,
and echocardiogram for all sarcoidosis patients, along with MRI, PET/nuclear
scans, and EPS for certain subsets of patients. Despite variable data to support
their efficacy, glucocorticoids should still be considered in the treatment plan
of CS. Antiarrhythmics in isolation are often ineffective in controlling
ventricular arrhythmias. Cardiac pacemakers have provided important therapy for
patients with conduction defects and implantable cardioverter defibrillator (ICD)
therapy provides the strongest insurance to prevent fatal arrhythmias from CS. A
recent consensus statement provides guidance for clinicians on the diagnosis and
management of arrhythmias associated with CS including indications for ICDs. The
use of pacemakers, ICD implantation and early implementation of corticosteroid
therapy have led to an improvement in the overall prognosis and clinical outcomes
of CS.
PMID- 25130889
TI - Optimising the detection and management of familial hypercholesterolaemia:
central role of primary care and its integration with specialist services.
AB - Familial hypercholesterolaemia (FH) is the most common monogenic lipid disorder
associated with premature coronary heart disease (CHD). However, the majority of
people with FH are undiagnosed or undertreated. Early cholesterol lowering
therapy reduces cardiovascular disease mortality in FH. Low awareness and
knowledge of FH in specialty and general practice highlights the need for
strategies to improve the detection and management of FH. We present an algorithm
describing a multidisciplinary approach to FH detection and management. We
highlight the role of primary care, and where GPs can work with preventive
cardiologists to improve care of FH. Novel strategies to detect index cases with
FH are presented including the community laboratory, highlighting patients at
high risk of FH, and targeted FH detection through searching the general practice
database. General practitioners request over 90% of LDL cholesterol measurements
in the community. Once an individual with FH is detected only a small proportion
of patients require specialty management with the majority of patients suitably
managed in primary care. However, it is crucial to screen family members, as 50%
of first-degree family members are expected to have FH due to the autosomal
dominant inheritance.
PMID- 25130890
TI - Patent foramen ovale influences the presentation of decompression illness in
SCUBA divers.
AB - BACKGROUND: Few have examined the influence of patent foramen ovale (PFO) on the
phenotype of decompression illness (DCI) in affected divers. METHODOLOGY: A
retrospective review of our database was performed for 75 SCUBA divers over a 10
year period. RESULTS: Overall 4,945 bubble studies were performed at our
institution during the study period. Divers with DCI were more likely to have
positive bubble studies than other indications (p<0.001). Major DCI was observed
significantly more commonly in divers with PFO than those without (18/1,000 v.s.
3/1,000, p=0.02). Divers affected by DCI were also more likely to require a
longer course of hyperbaric oxygen therapy (HBOT) if PFO was present (p=0.038).
If the patient experienced one or more major DCI symptoms, the odds ratio of PFO
being present on a transoesophageal echocardiogram was 3.2 (p=0.02) compared to
those who reported no major DCI symptoms. CONCLUSION: PFO is highly prevalent in
selected SCUBA divers with DCI, and is associated with a more severe DCI
phenotype and longer duration of HBOT. Patients with unexpected DCI with one or
more major DCI symptoms should be offered PFO screening if they choose to
continue diving, as it may have considerable prognostic and therapeutic
implications.
PMID- 25130891
TI - The FM/AM world is shaping the future of deep brain stimulation.
PMID- 25130892
TI - Ophthalmic complications of targeted cancer therapy and recently recognized
ophthalmic complications of traditional chemotherapy.
AB - As our understanding of cancer pathophysiology has increased, so have the number
of targeted therapeutic agents available. By targeting specific molecules
involved in tumorigenesis, targeted therapeutic agents offer the potential for
significant efficacy against tumor cells while minimizing the adverse effects. We
highlight the recently recognized ophthalmic complications of targeted cancer
therapy, as well as recently recognized complications of traditional
chemotherapeutic agents.
PMID- 25130893
TI - Pathogenesis of juvenile idiopathic arthritis associated uveitis: the known and
unknown.
AB - Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic
disease and the most prevalent systemic disorder in children with uveitis. The
current prevailing opinion is that JIA is a multifactorial, genetically
predisposed autoimmune disorder that can be influenced by environmental factors
and infections; the specific pathogenesis of JIA-associated uveitis is not
understood, however, nor has the relationship between the eye and joint
inflammation been established. Nevertheless, subtypes of JIA that are associated
with uveitis, oligoarthritis, polyarticular rheumatoid factor negative, and
psoriatic arthritis appear to have common pathogenicity. We summarize our current
knowledge regarding the pathogenesis of JIA-associated uveitis and discuss the
possible role of immune responses and cytokine involvement, genetic associations,
and the influence of external triggers in this disease-an association that is
supported by data obtained from arthritis research and experimental uveitis
models.
PMID- 25130894
TI - The promise of telemedicine.
AB - We have developed an extraordinary capability to capture and transmit digital
ocular imaging, enabling remote interpretation of every aspect of the eye. The
issues regarding telemedicine were primarily technical and procedural when this
journal first reviewed the topic in 1999. Fourteen years later, telemedicine
presents strikingly different challenges-legal, ethical, and professional. Some
"tele-ophthalmology" applications have now become a reliable part of daily
practice. Although it offers improved health care at lower cost to more people,
telemedicine could also radically transform the traditional doctor-patient
interaction.
PMID- 25130895
TI - The use of vermicompost in organic farming: overview, effects on soil and
economics.
AB - Vermicomposting is a process in which earthworms are used to convert organic
materials into humus-like material known as vermicompost. A number of researchers
throughout the world have found that the nutrient profile in vermicompost is
generally higher than traditional compost. In fact, vermicompost can enhance soil
fertility physically, chemically and biologically. Physically, vermicompost
treated soil has better aeration, porosity, bulk density and water retention.
Chemical properties such as pH, electrical conductivity and organic matter
content are also improved for better crop yield. Nevertheless, enhanced plant
growth could not be satisfactorily explained by improvements in the nutrient
content of the soil, which means that other plant growth-influencing materials
are available in vermicomposts. Although vermicomposts have been shown to improve
plant growth significantly, the application of vermicomposts at high
concentrations could impede growth due to the high concentrations of soluble
salts available in vermicomposts. Therefore, vermicomposts should be applied at
moderate concentrations in order to obtain maximum plant yield. This review paper
discusses in detail the effects of vermicompost on soil fertility physically,
chemically and biologically. Future prospects and economy on the use of organic
fertilizers in the agricultural sector are also examined.
PMID- 25130896
TI - Stearoyl-CoA desaturase regulates inflammatory gene expression by changing DNA
methylation level in 3T3 adipocytes.
AB - Adipocytes are one of the primary sources of inflammatory cytokines that drive
the low-grade inflammation associated with obesity and obesity-related diseases.
Stearoyl-CoA desaturase, a key adipogenic enzyme in rodents and humans, plays
significant role in the regulation of adipocyte inflammation via a mechanism that
involves the regulation of inflammatory gene expression. In the present study, we
tested the hypothesis that the stearoyl-CoA desaturase 1-related regulation of
gene expression might be driven by changes in DNA methylation. We showed that
stearoyl-CoA desaturase 1 overexpression causes the global hypomethylation of
DNA, even as early as 12h after the induction of differentiation, with the
greatest difference seen in mature adipocytes. In contrast, both the silencing of
stearoyl-CoA desaturase 1 gene expression by siRNA and inhibition of stearoyl-CoA
desaturase 1 activity resulted in DNA hypermethylation in 3T3-L1 adipocytes. The
analysis of the promoter methylation of 22 genes that are related to the
inflammatory response showed that the level of methylation of CpG sites in
interleukin-10 receptor a, interleukin-4 receptor a, interleukin-6 signal
transducer, and transforming growth factor beta 1 promoters was strongly related
to stearoyl-CoA desaturase 1 expression or activity. The changes in methylation
at CpG promoter sites correlated with differential expression of the
aforementioned genes. The results show that stearoyl-CoA desaturase 1 regulates
the level of DNA methylation in adipocytes and suggest that the mechanism by
which stearoyl-CoA desaturase 1 affects adipocyte inflammation may involve
changes in the methylation of inflammatory genes.
PMID- 25130897
TI - Allogeneic hematopoietic stem cell transplantation for T-prolymphocytic leukemia:
a report from the French society for stem cell transplantation (SFGM-TC).
AB - T-prolymphocytic leukemia (T-PLL), a rare aggressive mature T-cell disorder,
remains frequently resistant to conventional chemotherapy. Studies have suggested
that allogeneic hematopoietic stem cell transplantation (HSCT) might possibly
serve to consolidate the response to initial chemotherapy. The current report
summarizes the outcome of 27 T-PLL cases identified in the registry in French
Society for stem cell transplantation (SFGM-TC). Prior to HSCT, 14 patients were
in complete remission (CR), 10 in partial response, three refractory, or in
progression. Following HSCT, 21 patients achieved CR as best response. With a
median follow-up for surviving patients of 33 (range, 6-103) months, 10 patients
are still alive in continuous CR. Overall survival and progression-free survival
estimates at 3 yr were 36% (95% CI: 17-54%) and 26% (95% CI: 14-45%),
respectively. The relapse incidence after HSCT was 47% occurring at a median of
11.7 (range, 2-24) months. Overall cumulative incidence of transplant-related
mortality was 31% at 3 yr. These results suggest that HSCT may allow long-term
survival in patients with T-PLL following induction treatment; however, it is
associated with a significant rate of toxicity.
PMID- 25130898
TI - Self-awakening improves alertness in the morning and during the day after partial
sleep deprivation.
AB - The ability to awaken at a predetermined time without an alarm is known as self
awakening. Self-awakening improves morning alertness by eliminating sleep
inertia; however, the effects of self-awakening on daytime alertness and
alertness that has deteriorated as a result of sleep loss are unknown. The aim of
this study was to determine the effects of self-awakening on both morning and
daytime alertness after partial sleep deprivation. Fifteen healthy males without
the habit of self-awakening participated in a cross-over trial including forced
awakening and self-awakening conditions. In each condition, participants' sleep
was restricted to 5 h per night in their homes for 4 consecutive days. They
completed a psychomotor vigilance task and subjective ratings of sleepiness
immediately upon awakening each morning. On the fourth day, participants
completed subjective ratings of sleepiness, a psychomotor vigilance task and
sleep latency tests in the laboratory seven times at 1-h intervals during the
day. The response speed on the psychomotor vigilance task, in the morning and
during the day, was higher in the self-awakening than the forced awakening
condition. Our results showed that self-awakening improved alertness (assessed by
response speeds) by reducing sleep inertia and alleviated daytime sleepiness
heightened by partial sleep deprivation.
PMID- 25130900
TI - Correction of penile torsion and chordee by mobilization of urethra with
spongiosum in chordee without hypospadias.
AB - OBJECTIVE: To investigate the feasibility of correcting coexistent penile torsion
and chordee without hypospadias by mobilization of the urethra and spongiosum.
MATERIALS AND METHODS: A retrospective study of nine patients with simultaneous
penile torsion and chordee without hypospadias was undertaken between January
2006 and December 2012. During this period, a total of 364 cases of hypospadias
and 38 of chordee without hypospadias were operated on, making a total of 402
patients with hypospadias-related complexes. The same steps were used for
correction of both torque and chordee. After a circumcoronal incision, the penis
was fully degloved and the spongiosum with urethra was lifted up off the
cavernosa. Next, mobilization of the hypoplastic urethra with spongiosum was
extended into the glans. If chordee or torque persisted, urethral mobilization
was performed proximally up to the bulbar urethra, as required. Spongioplasty and
glansplasty were done and a per-urethral stent was kept in for three to five
days. RESULTS: The age of the patients ranged from 5 to 16 years (median 6
years). Penile torsion ranged from 30 degrees to 120 degrees , with a median of
75 degrees . Ventral chordee ranged from 45 degrees to 100 degrees , with a
median of 50 degrees . A ratio of 1:9.6 was found for chordee without hypospadias
compared to the total hypospadias cases, with an incidence of 9.5%. The ratio of
chordee without hypospadias with torsion compared to the total hypospadias cases
was 1:29. There was an incidence of chordee without hypospadias with penile
torsion of 3.5% in all patients with hypospadias. The ratio of chordee without
hypospadias with torsion to only chordee without hypospadias was 1:1.71, with an
incidence of 37.0%. Every step contributed to the correction of curvature and
torsion. Chordee was corrected in two patients by penile degloving and lifting of
the spongiosa off the urethral plate; three patients required additional
mobilization of the urethra into the glans. Another two patients needed proximal
urethral mobilization and one required a dorsal plication. In five patients,
torque was corrected by penile degloving, lifting of the spongiosa and
mobilization of the urethra into the glans; four patients required further
proximal urethral mobilization. All patients had excellent functional and
cosmetic results. No residual chordee or torque was observed in any patient on
follow-up at 12-24 months. CONCLUSION: The technique of distally mobilizing a
hypoplastic urethra with spongiosum from the corpora into the glans, and
proximally up to the bulbar region corrects moderate to severe chordee and
torsion with excellent cosmetic results. The incidence of torsion with chordee
without hypospadias was 3.5% of all cases of hypospadias.
PMID- 25130901
TI - The challenges in diagnosis and gender assignment in disorders of sex development
presenting to a pediatric surgical unit in a developing country: the role of
laparoscopy and simple tests for gender identity.
AB - OBJECTIVE: We aimed to assess how the diagnosis and determination of gender
identity of disorders of sex development (DSD) is different in a developing
country from Western medicine, and whether a pediatric surgery department can
determine the underlying diagnosis and use simple tools to determine the likely
gender identity (GI). MATERIAL AND METHODS: We reviewed the records of DSD
patients admitted to the Department of Pediatric Surgery, Chittagong Medical
College & Hospital (CMCH), Chittagong, Bangladesh, from January 2006 to December
2012 and performed a cross-sectional study on GI and gender-related behavior in
these patients during the year 2012. DSD boys and girls answered a GI interview
and had their gender role behavior assessed by observations of structural toy
play and analyzed for differences in scores. RESULTS: This cohort of DSD patients
presented in mid-childhood (6 months-16 years, mean 6.9 years) rather than
infancy, and 30% came from consanguineous unions. Congenital adrenal hyperplasia
(CAH) constituted only 11 of 50 (22%) of the DSD cohort, and not all families had
access to steroid hormone replacement. A simple assessment of GI and gender
related behavior allowed effective gender assignment, as there was significant
difference between DSD boys and girls in GI and gender-related behavior score.
CONCLUSIONS: DSD management in Bangladesh provides some unique challenges because
of limited resources. A national reference laboratory for biochemical and genetic
testing and development of a quaternary referral center for DSD patients will be
helpful. Continued use of the GI interview and gender-related behavior study will
enable effective interim decisions about diagnosis and management.
PMID- 25130899
TI - Cellular zinc levels are modulated by TRPML1-TMEM163 interaction.
AB - Mucolipidosis type IV (MLIV) is caused by loss of function mutations in the
TRPML1 ion channel. We previously reported that tissue zinc levels in MLIV were
abnormally elevated; however, the mechanism behind this pathologic accumulation
remains unknown. Here, we identify transmembrane (TMEM)-163 protein, a putative
zinc transporter, as a novel interacting partner for TRPML1. Evidence from yeast
two-hybrid, tissue expression pattern, co-immunoprecipitation, mass spectrometry
and confocal microscopy studies confirmed the physical association of TMEM163
with TRPML1. This interaction is disrupted when a part of TMEM163's N-terminus
was deleted. Further studies to define the relevance of their interaction
revealed that the plasma membrane (PM) levels of TMEM163 significantly decrease
when TRPML1 is co-expressed in HEK-293 cells, while it mostly localizes within
the PM when co-expressed with a mutant TRPML1 that distributes mostly in the PM.
Meanwhile, co-expression of TMEM163 does not alter TRPML1 channel activity, but
its expression levels in MLIV patient fibroblasts are reduced, which correlate
with marked accumulation of zinc in lysosomes when these cells are acutely
exposed to exogenous zinc (100 MUM). When TMEM163 is knocked down or when TMEM163
and TRPML1 are co-knocked down in HEK-293 cells treated overnight with 100 nm
zinc, the cells have significantly higher intracellular zinc levels than
untreated control. Overall, these findings suggest that TMEM163 and TRPML1
proteins play a critical role in cellular zinc homeostasis, and thus possibly
explain a novel mechanism for the pathological overload of zinc in MLIV disease.
PMID- 25130902
TI - Chironomidae and Oligochaeta for water quality evaluation in an urban river in
southeastern Brazil.
AB - Considering the importance of benthic macroinvertebrates for diagnosis of
variations in the ecological conditions of aquatic habitats, the aim of this
study was to investigate the structure of the Chironomidae and Oligochaeta
assemblages along an organic pollution gradient. The fauna specimens were
obtained with the use of artificial substrates, and the environmental variables
were recorded at five sites of the Sao Lourenco River, during 12 months. Metrics
of the assemblage and detrended correspondence analysis were used to verify the
response of the fauna to the pollution gradient. Procrustes analysis was used to
verify whether the data on the Chironomidae and Oligochaeta assemblages, as well
as the taxonomic and numerical resolution of these groups, provide similar
results in relation to the pollution gradient. The richness, evenness, and
taxonomic composition of the Chironomidae and Oligochaeta assemblages varied
significantly among the collection sites, with distinct conservation conditions.
Genera of the subfamilies Orthocladiinae and Tanypodinae were associated with the
sites upstream of the urban area, where the dissolved oxygen levels are higher.
Species of Oligochaeta and the genus Chironomus were associated with more
organically polluted sites. No concordance was observed in the response of the
Chironomidae and Oligochaeta assemblages in relation to the environmental
variables, indicating the need to use both groups in biomonitoring studies. On
the other hand, both the data on composition (presence or absence) and those on
the lowest taxonomic resolution (abundance of subfamilies) were effective to
diagnose the pollution gradient in the river studied. Therefore, when the
environmental conditions along a river's gradient are contrasting, we suggest the
use of the lowest taxonomic resolution of Chironomidae and Oligochaeta in
biomonitoring. That procedure considerably reduces the assessment time, besides
being a method that can be used by people not specializing in the taxonomy of
groups.
PMID- 25130903
TI - Labeo rosae (Cypriniformes: Cyprinidae) in the Congo basin: a relict distribution
or a historical introduction?
AB - Labeo rosae, a species with a native range in Southern Africa, was discovered in
the Congo basin by re-identification of two museum specimens previously
identified as Labeo mesops. The occurrence of this species in the upper Congo
implies a range extension of the species of more than 1000 km. Although the
species' distribution is mirrored by that of some other Cypriniformes, its
occurrence in the Congo might be due to introduction by humans.
PMID- 25130904
TI - Atopy does not affect the frequency of adenotonsillar hypertrophy and sleep
apnoea in children who snore.
AB - AIM: Viral respiratory infections and atopy have been implicated in the
pathogenesis of adenotonsillar hypertrophy and obstructive sleep apnoea (OSA),
but the role of atopy is controversial. We aimed to test our hypothesis that
atopy, expressed as physician-diagnosed eczema, was associated with
adenotonsillar hypertrophy and OSA among children who snored. METHODS: Data on
children who snored and were referred for polysomnography were reviewed. The
primary outcome measures were adenotonsillar hypertrophy and OSA. RESULTS: We
analysed data on 855 children with a mean age (+/-standard deviation) of 6.3 (+/
2.5) years and median obstructive apnoea-hypopnea index of 2.1 episodes per hour.
Of the 855 subjects, 133 (15.6%) had physician-diagnosed eczema, 591 (69.1%) had
adenoidal hypertrophy, 605 (70.8%) had tonsillar hypertrophy, 219 (25.6%) were
obese and 470 (55%) had OSA. Eczema was not related to adenoidal or tonsillar
hypertrophy after adjustment for gender and age, with odds ratios (OR) of 1.00
(95% confidence interval 0.67-1.49; p = 0.98) and 0.88 (95% confidence interval
0.59-1.32; p = 0.54), respectively. Similarly, eczema did not affect OSA
frequency after adjustment for adenoidal and tonsillar hypertrophy, obesity,
gender and age, with an adjusted OR of 0.82 (0.56-1.21; p = 0.32). CONCLUSIONS:
Atopy was not related to adenotonsillar hypertrophy or OSA in children who snore.
PMID- 25130905
TI - Arterial supply to the thyroid gland and the relationship between the recurrent
laryngeal nerve and the inferior thyroid artery in human fetal cadavers.
AB - The aim of this study was to identify the arterial supply to the thyroid gland
and the relationship between the inferior thyroid artery (ITA) and the recurrent
laryngeal nerve (RLN) in fetal cadavers using anatomical dissection. The anterior
necks of 200 fetuses were dissected. The origins of the superior thyroid artery
(STA) and the ITA and location of the ITA in relation to the entrance of the
thyroid lobe were examined. The relationship between the ITA and the RLN was
determined. The origins of the STA were classified as: external carotid artery,
common carotid artery (CCA), and the thyrolingual trunk. The origins of the ITA
were the thyrocervical trunk and the CCA. The ITA was absent on the left side in
two cases. The relationship of the RLN to the ITA fell into seven different
types. Type 1: the RLN lay posterior to the artery; right (42.5%), left (65%).
Type 2: the RLN lay anterior to the artery; right (40.5%), left (22.5%). Type 3:
the RLN lay parallel to the artery; right (11.5%), left (7%). Type 4: the RLN lay
between the two branches of the artery; right (1%), left (3.5%). Type 5: The
extralaryngeal branch of the RLN was detected before it crossed the ITA; right
(4.5%), left (0%). Type 6: the ITA lay between the two branches of the RLN; right
(0%), left (0.5%). Type 7: the branches of the RLN lay among the branches of the
ITA; right (0%), left (0.5%). The results from this study would be useful in
future thyroid surgeries.
PMID- 25130906
TI - Protein localization of epidermal growth factor in sheep ovaries and improvement
of follicle survival and antrum formation in vitro.
AB - The aims of this study were to characterize EGF protein expression in ovine
ovaries and to verify the effect of EGF on the in vitro development of isolated
pre-antral follicles. After collection, ovarian tissue was fixed for
immunohistochemical analysis. Additional pairs of ovaries were collected, and
secondary follicles were cultured for 18 days in alpha-MEM(+) (control) alone or
supplemented with EGF (1, 10 or 50 ng/ml). The immunostaining for EGF was
observed in oocytes from pre-antral and antral follicles, in granulosa cells of
primary and secondary follicles, as well as in cumulus and mural cells of antral
follicles. After 18 days, the results showed that treatment with 50 ng/ml EGF
significantly increased the percentage of morphologically normal follicles
compared with the control group (alpha-MEM(+) ) and significantly reduced the
precocious extrusion of oocytes and increased the percentage of antral follicles
compared with the control and 1 ng/ml EGF. All the treatments induced a
progressive and significant increase of the follicular diameter throughout the
period of culture. However, there were no significant differences in follicular
diameter or in the daily growth rate among treatments. In conclusion, this study
demonstrated the presence of EGF in ovine ovaries. Moreover, 50 ng/ml EGF
increased the percentage of normal follicles and improved antrum formation in
isolated ovine follicles after 18 days of in vitro culture.
PMID- 25130907
TI - DNA barcoding of wild edible mushrooms consumed by the ethnic tribes of India.
AB - Wild edible mushrooms are consumed by the tribes of Meghalaya in the North
Eastern region of India, as part of their ethnic cuisine because of their favored
organoleptic characteristics and traditionally known health benefits. Majority of
these mushrooms have not yet been characterized in detail and are slowly
shrinking in their natural habitats owing to anthropogenic factors and climate
change. In the present study, representative specimens of ten morphologically
distinct groups of wild edible mushrooms available in the traditional markets and
their respective forest habitats, were subjected to multi-loci molecular
characterization using SSU, ITS, RPB1 and RPB2 markers. The species identities
inferred for the ten mushroom types using the SSU marker matched their
morphological description in the case of four morphological groups only whereas
the ITS marker successfully resolved the species identity for nine out of the ten
mushroom groups under study. Both the protein coding gene markers RPB1 and RPB2
successfully resolved the species identity for three out of the ten
morphologically distinct groups. Finally the most likely identity of the wild
edible mushrooms under study has been suggested by matching their unique
morphological characteristics with the generated DNA barcoding data. The present
molecular characterization reveals the ten widely consumed wild mushroom types of
Meghalaya, India to be Gomphus floccosus, Lactarius deliciosus, Lactarius
volemus, Cantharellus cibarius, Tricholoma viridiolivaceum, Inocybe aff.
sphaerospora, Laccaria vinaceoavellanea, Albatrellus ellisii, Ramaria maculatipes
and Clavulina cristata. The final species identity generated by the ITS marker
matched more accurately with the morphological characteristics/appearance of the
specimens indicating the ITS region as a reliable barcode for identifying wild
edible mushrooms.
PMID- 25130908
TI - Cloning, expression and cellular localization of the Doublesex gene in the water
flea, Daphnia carinata, during different developmental stages.
AB - In this study, one of Doublesex genes from the common freshwater cladoceran
Daphnia carinata, designated DapcaDsx1, was cloned using primers based on
homologous sequences and rapid amplification of cDNA ends (RACE). qPCR was
employed to quantify differences in DapcaDsx1 expression between the different
sexual phases, with expression levels being higher in sexual females. The role of
DapcaDsx1 in the reproductive transformation was further investigated in
parthenogenetic-phase females and sexual-phase females using whole-mount in situ
hybridization. This cellular localization study showed specific expression of
DapcaDsx1 in the thoracic segments, second antenna and part of the ventral
carapace. Higher expression levels were exhibited in sexual females compared to
parthenogenetic females. This suggests that the DapcaDsx1 gene plays significant
roles in switching modes of reproduction and during sexual differentiation.
PMID- 25130909
TI - Diverse expression pattern of wheat transcription factors against abiotic
stresses in wheat species.
AB - Abiotic stress including drought and salinity affects quality and yield of wheat
varieties used for the production of both bread and pasta flour. bZIP, MBF1,
WRKY, MYB and NAC transcription factor (TF) genes are the largest transcriptional
regulators which are involved in growth, development, physiological processes,
and biotic/abiotic stress responses in plants. Identification of expression
profiling of these TFs plays a crucial role to understand the response of
different wheat species against severe environmental changes. In the current
study, expression analysis of TaWLIP19 (wheat version of bZIP), TaMBF1, TaWRKY10,
TaMYB33 and TaNAC69 genes was examined under drought and salinity stress
conditions in Triticum aestivum cv. (Yuregir-89), Triticum turgidum cv. (Kiziltan
91), and Triticum monococcum (Siyez). After drought stress application, all five
selected genes in Kiziltan-91 were induced. However, TaMBF1 and TaWLIP19 were the
only downregulated genes in Yuregir-89 and Siyez, respectively. Except TaMYB33 in
Siyez, expression level of the remaining genes increased under salt stress
condition in all Triticum species. For determination of drought response to
selected TF members, publicly available RNA-seq data were also analyzed in this
study. TaMBF1, TaWLIP19 and TaNAC69 transcripts were detected through in silico
analysis. This comprehensive gene expression analysis provides valuable
information for understanding the roles of these TFs under abiotic stresses in
modern wheat cultivars and ancient einkorn wheat. In addition, selected TFs might
be used for determination of drought or salinity-tolerant and susceptible
cultivars for molecular breeding studies.
PMID- 25130910
TI - Thermodynamic stability and kinetic inertness of a Gd-DTPA bisamide complex
grafted onto gold nanoparticles.
AB - Gold nanoparticles coated by gadolinium (III) chelates (Au@DTDTPA) where DTDTPA
is a dithiolated bisamide derivative of diethylenetriamine-N,N,N',N'',N''
pentaacetic acid (DTPA), constituted contrast agents for both X-ray computed
tomography and magnetic resonance imaging. In an MRI context, highly stable
Gd(3+) complexes are needed for in vivo applications. Thus, knowledge of the
thermodynamic stability and kinetic inertness of these chelates, when grafted
onto gold nanoparticles, is crucial since bisamide DTPA chelates are usually less
suited for Gd(3+) coordination than DTPA. Therefore, these parameters were
evaluated by means of potentiometric titrations and relaxivity measurements. The
results showed that, when the chelates were grafted onto the nanoparticle, not
only their thermodynamic stability but also their kinetic inertness were
improved. These positive effects were correlated to the chelate packing at the
nanoparticle surface that stabilized the corresponding Gd(3+) complexes and
greatly enhanced their kinetic inertness.
PMID- 25130911
TI - Ancient DNA evidence reveals that the Y chromosome haplogroup Q1a1 admixed into
the Han Chinese 3,000 years ago.
AB - OBJECTIVES: Y chromosome haplogroup Q1a1 is found almost only in Han Chinese
populations. However, it has not been found in ancient Han Chinese samples until
now. Thus, the origin of haplogroup Q1a1 in Han Chinese is still obscure. This
study attempts to provide answer to this question, and to uncover the origin and
paternal genetic structure of the ancestors of the Han Chinese. METHODS: Eighty
nine ancient human remains that were excavated from the presumed geographic
source of the Han Chinese and dated to approximately 3,000 years ago were treated
by the amelogenin gene polymerase chain reaction test, to determine their sex.
Then, Y chromosome single nucleotide polymorphisms were subsequently analyzed
from the samples detected as male. RESULTS: Samples from 27 individuals were
successfully amplified. Their haplotypes could be attributed to haplogroups N,
O*, O2a, O3a, and Q1a1. Analyses showed that the assigned haplogroup of each
sample is correlated to the suspected social status and observed burial custom
associated with the sample. CONCLUSIONS: The origins of the observed haplotypes
and their distribution in present day Han Chinese and in the samples suggest that
haplogroup Q1a1 was probably introduced into the Han Chinese population
approximately 3,000 years ago.
PMID- 25130913
TI - Local analyses of ionic liquid/solid interfaces by frequency modulation atomic
force microscopy and photoemission spectroscopy.
AB - Local analyses of ionic liquid/solid electrode interfaces at a controlled
electrode potential are of fundamental importance to understanding the origin and
properties of the electric double layer at the interfaces, which is necessary for
their application to electrochemical devices. This account summarizes our recent
achievements of such analyses by using the novel analytical tools of
electrochemical frequency modulation AFM (EC-FM-AFM) and electrochemical
photoemission spectroscopy (EC-PES). Rather stable stepped structures composed of
layers of ion pairs and softer solvation layers outside of the imaged layer were
clearly visualized by FM-AFM depending on the substrates. An extremely extended
diffusion layer was directly observed by EC-PES during the electrodeposition of
metal ion solutes.
PMID- 25130912
TI - Platelet activation biomarkers in Berkeley sickle cell mice and the response to
prasugrel.
AB - Vaso-occlusive crisis (VOC) is a common complication that occurs in sickle cell
disease (SCD) patients. Although underlying mechanisms of VOC remain unclear,
platelet activation has been associated with VOC. In the present study, plasma
adenine nucleotide measurements using LC-ESI-MS/MS showed that plasma ADP in the
Berkeley murine model of SCD was significantly higher (applox. 2.7-fold increase)
compared with control mice. Assessment of platelet activation markers using flow
cytometry indicated that in SCD mice at steady state (8 weeks old), circulating
platelets were partially activated and this tended to increase with age (15 weeks
old). The administration of prasugrel, a thienopiridyl P2Y12 antagonist, did not
affect the activation state of circulating platelets suggesting P2Y12 independent
mechanism of activation. In this murine SCD model, ex vivo addition of ADP or
PAR4 TRAP resulted in further platelet activation as assessed by expression of
activated GPIIb/IIIa and P-selectin both at 8 and 15 weeks. In 15 weeks old SCD
mice, agonist-induced increases in activation markers were enhanced compared to
control mice. Oral administration of prasugrel effectively inhibited ex vivo
platelet activation consistent with clinical data in patients with SCD. In
conclusion, in the Berkeley murine model of SCD, we found evidence of basal and
agonist-stimulated platelet activation which could in part be attenuated by
prasugrel. These data are consistent with observations made in patients with SCD
and suggest possible utility of this murine model and prasugrel therapy in
exploring treatment options for patients with SCD.
PMID- 25130914
TI - Inability to Measure M-Protein With Capillary Zone Electrophoresis (CAPPILLARYS
2) in Tracings With NonDiscernable Peaks.
AB - BACKGROUND: We performed a retrospective study to illustrate the challenges with
quantifying monoclonal (M)-protein in the cases of serum protein capillary zone
electrophoresis (SPCZE) where no discernable peak is apparent. MATERIALS AND
METHODS: We retrospectively reviewed 160 serum immunofixation electrophoresis
(SIFE) that were performed at Memorial Hermann Hospital-Texas Medical Center
between October 2013 and November 2013 and we identified the positive SIFE
results. The corresponding SPCZE of the positive SIFE were retrieved and
evaluated for the ability to quantify M-proteins in them. We define the ability
to quantify M-protein as the ability for the operator of the SPCZE to identify a
discernable peak and to be able to manually gate the area under the peak.
RESULTS: Twenty-two cases of SIFE detected a monoclonal immunoglobulin. Of the
corresponding 22 SPCZE, we could not quantify the M-protein in 6 (27.3%) of the
cases. CONCLUSION: We have shown several cases where we were not able to quantify
the M-protein with SPCZE. This poses a challenge in the diagnosis and management
of these patients.
PMID- 25130915
TI - Human papillomavirus genotype distribution in invasive cervical cancer in Bosnia
and Herzegovina.
AB - PURPOSE: Countries of the former Yugoslavia bear some of the highest cervical
cancer burden in Europe. In Bosnia and Herzegovina (B&H), data on human
papillomavirus (HPV) genotype distribution among cervical cancer cases is scarce.
This baseline information is critical in order to evaluate the impact of
prophylactic HPV vaccines. This study aims to provide specific information for
B&H. METHODS: The final analysis comprised 283 cases of invasive cervical cancer
identified at the Polyclinic for Laboratory Diagnostic, University Clinical
Center Tuzla in B&H between 1984 and 2004. HPV was detected through amplification
of HPV DNA using SPF-10 broad spectrum primers followed by deoxyribonucleic acid
enzyme inmunoassay and genotyping by reverse line probe assay (LiPA(25), version
1). RESULTS: Most cases (92.2%) were histologically classified as squamous cell
carcinoma (SCC). A total of 268 cases (94.7%) were positive for HPV. Infections
were mainly present as single (95.5%) and HPV16 and 18 accounted for 77.8% of the
positive cases. The next most common HPV types were HPV45 (4.4%), HPV33 (3.1%),
HPV51 (2.3%) and HPV31 (2.2%). The mean age of cases infected with the seven most
common types worldwide (HPV16/18/45/31/33/52/58) was 51.1 (SD=11.6), six years
younger than the one for cases infected with other types (56.3, SD=12.9).
CONCLUSIONS: Available HPV vaccines could potentially prevent 77.8% of Bosnian
cervical cancer cases (i.e. those associated with HPV16/18). If the reported
magnitude of the cross-protection of licensed vaccines for non-vaccine HPV types
is long lasting, an additional 6 to 10% of cases could be prevented.
PMID- 25130917
TI - Vacuum-free, maskless patterning of Ni electrodes by laser reductive sintering of
NiO nanoparticle ink and its application to transparent conductors.
AB - We introduce a method for direct patterning of Ni electrodes through selective
laser direct writing (LDW) of NiO nanoparticle (NP) ink. High-resolution Ni
patterns are generated from NiO NP thin films by a vacuum-free, lithography-free,
and solution-processable route. In particular, a continuous wave laser is used
for the LDW reductive sintering of the metal oxide under ambient conditions with
the aid of reducing agents in the ink solvent. Thin (~ 40 nm) Ni electrodes of
glossy metallic surfaces with smooth morphology and excellent edge definition can
be fabricated. By applying this method, we demonstrate a high transmittance
(>87%), electrically conducting panel for a touch screen panel application. The
resistivity of the Ni electrode is less than an order of magnitude higher
compared to that of the bulk Ni. Mechanical bending test, tape-pull test, and
ultrasonic bath test confirm the robust adhesion of the electrodes on glass and
polymer substrates.
PMID- 25130916
TI - Using self-reported health measures to predict high-need cases among Medicaid
eligible adults.
AB - OBJECTIVE: To assess the ability of different self-reported health (SRH) measures
to prospectively identify individuals with high future health care needs among
adults eligible for Medicaid. DATA SOURCES: The 1997-2008 rounds of the National
Health Interview Survey linked to the 1998-2009 rounds of the Medical Expenditure
Panel Survey (n = 6,725). STUDY DESIGN: Multivariate logistic regression models
are fitted for the following outcomes: having an inpatient visit; membership in
the top decile of emergency room utilization; and membership in the top cost
decile. We examine the incremental predictive ability of six different SRH
domains (health conditions, mental health, access to care, health behaviors,
health-related quality of life [HRQOL], and prior utilization) over a baseline
model with sociodemographic characteristics. Models are evaluated using the c
statistic, integrated discrimination improvement, sensitivity, specificity, and
predictive values. PRINCIPAL FINDINGS: Self-reports of prior utilization provide
the greatest predictive improvement, followed by information on health conditions
and HRQOL. Models including these three domains meet the standard threshold of
acceptability (c-statistics range from 0.703 to 0.751). CONCLUSIONS: SRH measures
provide a promising way to prospectively profile Medicaid-eligible adults by
likely health care needs.
PMID- 25130918
TI - Increase in skin surface elasticity in normal volunteer subjects following the
use of copper oxide impregnated socks.
AB - BACKGROUND: Copper is an essential mineral involved in the formation and
stabilisation of extracellular skin proteins. As copper can be absorbed through
intact skin, we reasoned that using socks containing copper-impregnated fibres
may have an effect on skin elasticity. METHODS: A double blind, placebo
controlled study was conducted in which one group of healthy volunteers (n = 32)
wore socks with fibres containing microscopic copper oxide particles and the
other group wore identical socks without copper oxide (n = 28). The socks were
worn for at least 10 h a day for 4 weeks. Skin elasticity measurements were taken
from three separate test sites on the side of the ankle using a Cutometer at
baseline and after 2 and 4 weeks of product use. RESULTS: There was an increase
in the mean net skin elasticity (R5) of 6.4% (P = 0.6) and 31.4% (P = 0.004)
after 2 and 4 weeks respectively, in the group of individuals that used the
copper oxide containing socks, but no increase in the group of individuals that
used the control socks. Similarly, there was an increase in the mean biological
elasticity (R7 values) of 3% (P = 0.55) and 20.7% (0.014) after 2 and 4 weeks,
respectively, only in the group of individuals that used the copper oxide
containing socks. The differences between treatments (i.e. socks used) were
statistically significant at 4 weeks (P = 0.0058 and P = 0.0327 for R5 and R7,
respectively). CONCLUSION: Using copper oxide containing socks results in an
increase in skin elasticity of the feet.
PMID- 25130919
TI - Effects of diabetes mellitus on left atrial volume and functions in normotensive
patients without symptomatic cardiovascular disease.
AB - PURPOSE: Left atrial (LA) size has been shown to be a predictor of adverse
cardiovascular outcomes. The aim of the study was to evaluate the direct effect
of diabetes mellitus (DM) on left atrial volume and phasic functions by using
real-time three-dimensional echocardiography (RT3DE) in a population of patients
free of symptomatic cardiovascular disease and hypertension. METHODS:
Comprehensive transthoracic echocardiographic examination was performed on 40
consecutive patients with DM (20 male, age: 50.5+/-7.3 years) and 40 healthy
controls (20 male, age: 48.4+/-6.7 years). In addition to conventional 2D
echocardiographic measurements RT3DE was performed to assess LA volumes and
phasic functions. RESULTS: There were no significant difference between groups
regarding parameters reflecting LV systolic function as LV diameters and ejection
fraction. However, regarding parameters reflecting LV diastolic function;
transmitral deceleration time and E/E' ratio values were significantly higher and
majority of early diastolic tissue Doppler velocity values were significantly
lower in diabetic patients compared with controls. RT3DE demonstrated
significantly higher LA maximum and minimum volumes for diabetic patients
compared with controls (40.9+/-11.9 vs 34.6+/-9.3 mL, p: 0.009 and 15.6+/-5.9 vs
11.9+/-4.6 mL, p: 0.002, consecutively). LA total emptying fraction (TEF),
expansion index (EI) and active emptying fraction (AEF) were found to be
significantly lower in diabetics reflecting depressed LA reservoir and pump
functions. There was no significant difference between groups regarding passive
emptying fraction (PEF) which is assumed to be a marker of left atrial conduit
function. CONCLUSION: Patients with type 2 diabetes mellitus were found to have
increased LA volume and impaired atrial compliance and contractility. Evaluation
of asymptomatic diabetic patients by using RT3DE atrial volume analysis may
facilitate recognition of subtle myocardial alterations related with type 2
diabetes.
PMID- 25130924
TI - The cultural dimension of tightness-looseness: An analysis of situational
constraint in Estonia and Greece.
AB - The importance of tightness-looseness as a dimension that explains a considerable
amount of variance between cultures was demonstrated by Gelfand et al. (2011).
Tight nations have many strong norms and a low tolerance of deviant behaviour,
whereas loose nations have weak social norms and a high tolerance of deviant
behaviour. The main aim of the current studies was to examine situational
constraint in Estonia and Greece: that is, how the cultural dimension of
tightness-looseness is manifested in everyday situations in those two countries.
The findings of a questionnaire study (Study 1) suggested that, in general, there
is higher constraint across everyday situations in Greece than in Estonia, but
situational constraint in Greece is especially strong in school and
organisational settings where people have hierarchically structured roles. The
results of an observational study (Study 2) revealed a relatively high agreement
between appropriateness of certain behaviours as judged by the respondents in
Study 1 and the frequencies of observed behaviours in the two countries. Our
findings suggest that the strength of situations may substantially vary both
within and across cultures, and that the attitudes of the members about
situational strength in their respective cultures are in concordance with
observations of situations by neutral observers in how people in general behave
in their culture.
PMID- 25130920
TI - Lixisenatide plus basal insulin in patients with type 2 diabetes mellitus: a meta
analysis.
AB - AIMS: The efficacy of the once-daily prandial GLP-1 receptor agonist lixisenatide
plus basal insulin in T2DM was assessed by pooling results of phase III trials.
METHODS: A meta-analysis was performed of results from three trials in the
GetGoal clinical program concerning lixisenatide or placebo plus basal insulin
with/without OADs. The primary endpoint was change in HbA1c from baseline to week
24. Secondary endpoints were change in PPG, FPG, insulin dose, and weight from
baseline to week 24. Hypoglycemia rates and several composite endpoints were
assessed. RESULTS: Lixisenatide plus basal insulin was significantly more
effective than basal insulin alone at reducing HbA1c at 24 weeks. Composite and
secondary endpoints were improved significantly with lixisenatide plus basal
insulin, with the exception of FPG, which showed no significant difference
between the groups. Lixisenatide plus basal insulin was associated with an
increased incidence of hypoglycemia versus basal insulin alone. CONCLUSIONS:
Lixisenatide plus basal insulin resulted in significant improvement in glycemic
control versus basal insulin alone, particularly in terms of controlling PPG.
Prandial lixisenatide in combination with basal insulin is a suitable option for
treatment intensification in patients with T2DM insufficiently controlled with
basal insulin, as these agents have complementary effects on PPG and FPG,
respectively.
PMID- 25130925
TI - Cystic lesions in the kidney of flower horn fish, hybrid cichlid.
PMID- 25130926
TI - First report of a rare mutation in a Polish patient with painful late-onset
transthyretin amyloidosis.
PMID- 25130927
TI - Individual factors enhance poor health-related quality of life outcome in
multiple sclerosis patients. Significance of predictive determinants.
AB - BACKGROUND: Individual factors in multiple sclerosis (MS) patients may modify the
reliability of health-related quality of life (HRQOL) assessment. Knowledge of
these effects may enable physicians to identify patients at risk for poor
perceived health. OBJECTIVE: To investigate what individual factors may interact
with MS symptoms and their severity to modify the reliability of HRQOL
assessment; to explore the predictive values of the significant variables
identified. METHODS: HRQOL was assessed in 57 patients by the 36-Item Short Form
Health Survey (SF-36). The Physical Component Summary and Mental Component
Summary were dichotomized and applied as dependent variables for logistic
regression analysis. The Functional Independence Measure (FIM), Expanded
Disability Status Scale (EDSS), Fatigue Severity Scale (FSS), Cognitive
Behavioral Assessment (CBA) and specific individual factors were tested as
independent variables. Two-way contingency tables were used to calculate the
predictive values. RESULTS: Unemployment, smoking, and night waking were the most
significant individual factors. Introversion, physical pain and difficulty
falling asleep were also significant. EDSS-total >=2, EDSS-pyramidal >=2, FIM
<=123, FSS >=5, depressive manifestations and bowel/bladder dysfunction were
significant MS-related determinants. Sensitivity and specificity differed widely
for each variable. CONCLUSIONS: Individual factors have relevance in HRQOL
assessment. Their identification may help physicians construct the patient's risk
profile. Sensitivity and specificity add weight to the significance of variables.
PMID- 25130928
TI - Anatomical localization of p53 mutated tumors: A radiographic study of human
glioblastomas.
AB - Accumulating evidence has suggested that tumor location is linked to the genetic
profile of gliomas. Therefore, the aim of this study was to investigate the
anatomical characteristics of p53-mutated glioblastomas. We also sought to
provide new insight into the possible niche locations of cells of glioblastoma
origin. In order to accomplish this, preoperative magnetic resonance images from
163 patients with primary glioblastomas were retrospectively analyzed. All tumors
were manually marked and registered to the standard space. Using the voxel-based
lesion-symptom mapping approach, voxels exhibiting the strongest correlations
with p53 mutants were identified. T-values of voxels that were greater than 95%
of the permutations were factored into the results of the mapping analysis.
Distinct anatomical characteristics between p53-mutated and wild-type
glioblastomas were demonstrated using this approach. More specifically, we found
that p53-mutated glioblastomas were preferentially located in the frontal lobe in
the area surrounding the rostral extension of the lateral ventricles. The
distinct anatomical characteristics of p53-mutated and wild-type glioblastomas
provide further evidence that these gliomas arise from distinct niche locations.
PMID- 25130929
TI - Increased proinflammatory cytokines in sera of patients with multifocal motor
neuropathy.
AB - BACKGROUND: Multifocal motor neuropathy (MMN) is characterized by clinical
improvement with intravenous immunoglobulin and the frequent detection of anti
ganglioside antibodies. However, the immunological background of the neuronal
damage in MMN is still unclear. OBJECTIVE: The aim of this study is to
investigate abnormalities in the cytokine and chemokine profiles of MMN patients.
METHODS: Sera from 16 patients with MMN, 16 patients with sporadic amyotrophic
lateral sclerosis (ALS), and 15 patients with other non-inflammatory neurological
diseases (ONDs) were analyzed for 27 cytokines and chemokines using a multiplex
bead array. We also checked whether the altered cytokine/chemokine profile in the
MMN group differed significantly in the presence or absence of abnormal
electrophysiological findings. RESULTS: Serum IL-1Ra, IL-2, G-CSF, TNF-alpha, and
TNFR1 levels were significantly higher in the MMN group than in the ONDs group.
Of these, G-CSF and TNF-alpha also showed significant increases compared to the
ALS group. Serum G-CSF and TNF-alpha levels were significantly higher in MMN
patients presenting with focal demyelination including conduction block than in
patients without any focal demyelination. CONCLUSIONS: Proinflammatory cytokines
may contribute to peripheral nerve demyelination in MMN.
PMID- 25130930
TI - Polymyositis in solid organ transplant recipients receiving tacrolimus.
AB - Tacrolimus, also known as FK506, is an immunosuppressive agent widely used for
the prevention of acute allograft rejection in organ transplantation and for the
treatment of immunological diseases. This study reports two male patients who
underwent solid organ transplantation (liver and kidney). After transplant, the
patients received continuous immunosuppressive therapy with oral tacrolimus and
later presented clinical manifestations and laboratory signs of myopathy. Muscle
biopsies of both patients clearly documented an inflammatory myopathy with the
histological features of polymyositis including CD8+ T cells which invaded
healthy muscle fibers and expressed granzyme B and perforin, many CD68+
macrophages and MHC class I antigen upregulation on the surface of most fibers.
Because of the temporal association while receiving tacrolimus and since other
possible causes for myopathy were excluded, the most likely cause of polymyositis
in our patients was tacrolimus toxicity. We suggest that patients on tacrolimus
should be carefully monitored for serum CK levels and clinical signs of muscle
disease.
PMID- 25130931
TI - Synthesis of octitols and the respective amino-derivatives from 'organo-aldols'.
AB - Two diastereoisomeric keto-octoses, obtained in the reaction of 2,3:4,5-diacetone
D-arabinose with protected dihydroxyacetone catalyzed with L- or D-proline, were
converted into octitols by stereoselective reduction of the carbonyl group with
zinc borohydride and final deprotection. The study on the preparation of the
respective amino-derivatives by reductive amination of these organo-adducts is
presented; stereochemical aspects of these processes are discussed.
PMID- 25130933
TI - Safe storage of radical initiators within a polyaromatic nanocapsule.
AB - 2,2'-Azobisisobutyronitrile and its derivatives are standard reagents for polymer
and organic syntheses that generate radical species on stimuli by light or heat.
Radical initiators like the azo compounds are unstable so that they should be
kept in the dark at low temperature to avoid photochemical and thermal
decomposition as well as accidental explosion. Here we report the spontaneous and
quantitative encapsulation of the radical initiators by a supramolecular
nanocapsule in aqueous solution. We demonstrate the remarkable stability of the
initiators toward light and heat in the well-defined cavity shielded by the
polyaromatic capsule shell. The incarcerated and stabilized initiators can be
directly utilized for the radical polymerization of olefins on spontaneous
release of the initiators from the capsule under the reaction conditions.
PMID- 25130932
TI - The visual system in eyelid myoclonia with absences.
AB - OBJECTIVE: To investigate the functional and structural brain correlates of
eyelid myoclonus and absence seizures triggered by eye closure (eye closure
sensitivity [ECS]). METHODS: Fifteen patients with eyelid myoclonus with absences
(EMA, Jeavons syndrome), 14 patients with idiopathic generalized epilepsies (IGE)
without ECS, and 16 healthy controls (HC) underwent an electroencephalography
(EEG)-correlated functional magnetic resonance imaging (fMRI) and voxel brain
morphometry (VBM) protocol. The functional study consisted of 30-second epochs of
eyes-open and eyes-closed conditions. The following EEG events were marked and
the relative fMRI maps obtained: (1) eye closure times, (2) spontaneous blinking,
and (3) spontaneous and eye closure-triggered spike and wave discharges (SWD; for
EMA and IGE). Within-group and between-groups comparisons were performed for fMRI
and VBM data as appropriate. RESULTS: In EMA compared to HC and IGE we found: (1)
higher blood oxygenation level-dependent (BOLD) signal related to the eye closure
over the visual cortex, the posterior thalamus, and the network implicated in the
motor control of eye closure, saccades, and eye pursuit movements; and (2)
increments in the gray matter concentration at the visual cortex and thalamic
pulvinar, whereas decrements were observed at the bilateral frontal eye field
area. No BOLD differences were detected when comparing SWD in EMA and IGE.
INTERPRETATION: Results demonstrated altered anatomo-functional properties of the
visual system in EMA. These abnormalities involve a circuit encompassing the
occipital cortex and the cortical/subcortical systems physiologically involved in
the motor control of eye closure and eye movements. Our work supports EMA as an
epileptic condition with distinctive features and provides a contribution to its
classification among epileptic syndromes.
PMID- 25130934
TI - Patulin reduction in apple juice by inactivated Alicyclobacillus spp.
AB - This study aimed to investigate the reduction of patulin (PAT) in apple juice by
12 inactivated Alicyclobacillus strains. The reduction rate of PAT by each strain
was determined by high-performance liquid chromatography (HPLC). The results
indicated that the removal of PAT was strain specific. Alicyclobacillus
acidoterrestris 92 and A. acidoterrestris 96 were the most effective ones among
the 12 tested strains in the removal of PAT. Therefore, these two strains were
selected to study the effects of incubation time, initial PAT concentration and
bacteria powder amount on PAT removal abilities of Alicyclobacillus. The highest
PAT reduction rates of 88.8 and 81.6% were achieved after 24-h incubation with
initial PAT concentration of 100 MUg l(-1) and bacteria powder amount of 40 g l(
1) , respectively. Moreover, it was found that the treatment by these 12
inactivated Alicyclobacillus strains had no negative effect on the quality
parameters of apple juice. Similar assays were performed in supermarket apple
juice, where inactivated Alicyclobacillus cells could efficiently reduce PAT
content. Taken together, these data suggest the possible application of this
strategy as a means to detoxify PAT-contaminated juices. SIGNIFICANCE AND IMPACT
OF THE STUDY: Inactivated Alicyclobacillus cells can efficiently reduce patulin
concentration in apple juice. It provides a theoretical foundation for recycling
of Alicyclobacillus cells from spoiled apple juice to reduce the source of
pollution and the cost of juice industry. This is the first report on the use of
Alicyclobacillus to remove patulin from apple juice.
PMID- 25130935
TI - RBC alloimmunization and double alloantibodies in thalassemic patients.
AB - PURPOSE: Alloimmunization is a common consequence of chronic blood transfusion.
Double alloantibody production may complicate the condition of such patients
especially for finding matched blood. In this study, we evaluated the frequency
of alloantibodies in thalassemic patients with previous history of transfusion
reactions. SAMPLES AND METHODS: This study was performed on 441 multiply
transfused thalassemia patients Antibody screening test was carried out using
three cell-panel by gel method. Positive patients were followed up for antibody
identification using 11-cell panel. Direct combs' test was performed to detect
auto antibodies. RESULTS: In a total of 441 cases (362 thalassemia major and 79
intermedia), 234 were males (53.1%) and 207 females (46.9%); mean age 22 years,
range 3-61 years. Alloimmunization was detected in 50(11.3%) patients, including
37(74%) patients with one alloantibody, 8(16%) with two antibodies, 4(8%)
patients with unknown antibodies and one patient (2%) with autoantibody. The most
common alloantibodies were anti-Rh antibodies (-E/e/C/c/Cw) (26%), anti-K (28%),
anti-D (16%), and anti-Colton (4%). Double antibodies were detected in eight out
of 50 patients, including: Anti-D+anti-C (8%), anti-D+anti-E (2%), anti-Kell+anti
D (2%), and anti-Kell+KPa (2%). A significant association was observed between
the transfusion reaction history and the alloantibody detection results (p <
0.05). CONCLUSION: Antibody production against RBC antigens makes hard condition
in regular blood transfusion. Double antibodies production may more complicate
this situation. Thus, it is advisable to phenotype patients and matches the red
cells in multiply transfused thalassemia patients.
PMID- 25130936
TI - A population-based study of incidence, risk factors, clinical spectrum, and
outcomes of ischemic colitis.
AB - BACKGROUND & AIMS: Little is known about progression of ischemic colitis (IC)
among unselected patients. We aimed to estimate the incidence, risk factors, and
natural history of IC in a population-based cohort in Olmsted County, Minnesota.
METHODS: We performed a retrospective population-based cohort and nested case
control study of IC. Each IC case was matched to 2 controls from the same
population on the basis of sex, age, and closest registration number. Conditional
logistic regression, the Kaplan-Meier method, and proportional hazards regression
were used to assess comorbidities, estimate survival, and identify
characteristics associated with survival, respectively. RESULTS: Four hundred
forty-five county residents (median age, 71.6 years; 67% female) were diagnosed
with IC from 1976 through 2009 and were matched with 890 controls. The age
adjusted and sex-adjusted incidence rates of IC nearly quadrupled from 6.1
cases/100,000 person-years in 1976-1980 to 22.9/100,000 in 2005-2009. The odds
for IC were significantly higher among subjects with atherosclerotic diseases;
odds ratios ranged from 2.6 for individuals with coronary disease to 7.9 for
individuals with peripheral vascular disease. Of IC cases, 59% survived for 5
years (95% confidence interval, 54%-64%), compared with 90% of controls (95%
confidence interval, 88%-92%). Age >40 years, male sex, right-sided colon
involvement, concomitant small bowel involvement, and chronic obstructive
pulmonary disease were all independently associated with mortality (P < .05).
CONCLUSIONS: The incidence of IC increased during the past 3 decades in a
population-based cohort in Minnesota. IC typically presents in older patients
with multiple comorbidities and is associated with high in-hospital mortality
(11.5%) and rates of surgery (17%).
PMID- 25130938
TI - What gastroenterologists should know about testing patients with eosinophilic
esophagitis for food allergies.
PMID- 25130939
TI - Outcomes of children after esophagogastroduodenoscopy for chronic abdominal pain.
PMID- 25130937
TI - Long-term use of antibiotics and proton pump inhibitors predict development of
infections in patients with cirrhosis.
AB - BACKGROUND & AIMS: Bacterial infections, particularly repeated infections, are
significant causes of morbidity and mortality among patients with cirrhosis. We
investigated and characterized risk factors for repeat infections in these
patients. METHODS: In a prospective study, we collected data from 188 patients
hospitalized with cirrhosis and infections and enrolled in the North American
Consortium for the Study of End-Stage Liver Disease (12 centers). Patients were
followed up for 6 months after hospital discharge and data were analyzed on type
of infections and factors associated with subsequent infections. RESULTS: Six
months after hospital discharge, 14% of subjects had received liver transplants,
27% died, and 59% were alive without liver transplantation. After discharge, 45%
had subsequent infections, but only 26% of the subsequent infections occurred at
the same site. Compared with patients not re-infected, patients with repeat
infections were older and a higher proportion used proton pump inhibitors (PPIs)
(P = .006), rifaximin (P < .001), or prophylactic therapy for spontaneous
bacterial peritonitis (SBP) (P < .001). Logistic regression showed that SBP
prophylaxis (odds ratio [OR], 3.44; 95% confidence interval [CI], 1.56-7.63), PPI
use (OR, 2.94; 95% CI, 1.39-6.20), SBP at hospital admission (OR, 0.37; 95% CI,
0.15-0.91), and age (OR, 1.06; 95% CI, 1.02-1.11) were independent predictors of
subsequent infections. CONCLUSIONS: Patients hospitalized with cirrhosis and
infections are at high risk for subsequent infections, mostly at different sites,
within 6 months of index infection resolution. Those at highest risk include
previously infected older patients receiving PPIs and/or SBP prophylaxis,
although these associations do not prove that these factors cause the infections.
New strategies are needed to prevent infections in patients with cirrhosis.
PMID- 25130941
TI - COSAN as a molecular imaging platform: synthesis and "in vivo" imaging.
AB - A labelling method for the covalent attachment of radioiodine to the boron-rich 8
I-cobaltabisdicarbollide (I-COSAN) and a bi-functional (iodine and PEG) COSAN
derivative, [3,3'-Co(8-I-1,2-C2B9H10)(8'-(OCH2CH2)2COOC6H5-1',2'-C2B9H10)], is
reported. Biodistribution studies in rodents using dissection/gamma counting and
in vivo nuclear imaging have been performed. The general strategy reported here
can be applied in the future to COSAN derivatives bearing a wide range of
functionalities.
PMID- 25130940
TI - Cerebral venous thrombosis after embolization of pediatric AVM with jugular bulb
stenosis or occlusion: management and prevention.
AB - PURPOSE: Thrombosis of cerebral arteriovenous malformation after embolization is
rare, but can involve the normal venous network with extensive venous thrombosis.
We report angioarchitecture findings, our management and prevention strategy for
this complication in pediatric AVMs. METHODS: In this 5.5-year retrospective
series, we reviewed records of 13 patients under 15 years who were anticoagulated
after embolization. In our initial experience 4 children who didn't receive any
prophylactic anticoagulation presented with extensive venous thrombosis after
embolization (group 1). Following this, nine children with similar
angioarchitecture and embolization modalities were treated with prophylactic
anticoagulation immediately after embolization (group 2). We analyzed the type of
AVM, angioarchitecture, dose of prophylactic anticoagulant,
efficacy/complications of treatment and late outcome. RESULTS: All patients in
group 1 had severe jugular bulb stenosis/occlusion associated with cerebral
venous dilatation. In group 2 with similar angioarchitecture, only three patients
(33%) developed extensive thrombosis. In both groups, thrombosis occurred within
two days of treatment in six children and two weeks in one child. The diagnosis
was suspected on intracranial hypertension in five patients and occulomotor
disorder in one. One was asymptomatic. All children were treated with therapeutic
doses of LMWH (anti-Xa: 0.5-1). No hemorrhagic complications occurred. Good
venous remodeling was observed in all but one patient. CONCLUSION:
Anticoagulation in extensive venous thrombosis after AVM embolization in children
appears to be safe and effective. In cases with angioarchitectural features of
dilatation of the cerebral venous network and occlusion/severe stenosis of the
jugular bulbs, full dose anticoagulation may be required to prevent thrombosis.
PMID- 25130942
TI - Tracheal rupture in complicated delivery: a case report and review of the
literature.
AB - A case of distal tracheal rupture is described, literature review reveals two
previously reported cases of neonatal distal tracheal rupture, as well as 14
cases of anterior subglottic rupture. All patients had shoulder dystocia, and 59%
had associated brachial plexus injury. Delayed diagnosis (>3 days) was common in
the distal tracheal group (66%), compared to 0% in the anterior subglottic group.
The 2 distal tracheal rupture patients were initially managed conservatively, but
ultimately required open repair. Distal tracheal rupture is exceedingly rare and
more difficult to diagnose and manage than the more common anterior subglottic
rupture.
PMID- 25130943
TI - Letter to the Editor regarding "In reference to the value of resident
presentations at scientific meetings".
PMID- 25130944
TI - Letter to the Editor regarding "Otoacoustic emissions in newborn hearing
screening: a systematic review of the effects of different protocols on test
outcomes".
PMID- 25130945
TI - Intra-thyroidal hemangioma--a rare congenital anomaly: case presentation and
literature review.
AB - Infantile hemangiomas (IH) present and evolve in a predictable way. In certain
cases, however, they can be of clinical significance. IHs in the airway can cause
significant respiratory distress. We present the first reported case of an
intrathyroidal hemangioma to cause significant respiratory distress, which was
successfully treated with propranolol and dexamethasone. A review of the
literature was also performed.
PMID- 25130946
TI - Velopharyngeal dysfunction in children with Prader-Willi syndrome after
adenotonsillectomy.
AB - INTRODUCTION: Prader-Willi syndrome (PWS) is a rare genetic disorder with an
incidence rate of 1 in 10,000-30,000. Patients with PWS typically have symptoms
related to hypotonia, obesity, and hypothalamic dysfunction. A high rate of
obstructive sleep apnea (OSA) is found among this population of patients.
Adenotonsillectomy has been advocated as a first line approach for treatment of
OSA in patients with PWS. Velopharyngeal dysfunction (VPD) is a known
complication of adenotonsillectomy. VPD can also be present in patients with
global hypotonia, such as those with PWS. The objective of this study is to
review the occurrence of VPD in patients with PWS after adenotonsillectomy for
OSA. METHODS: A retrospective review was performed of all patients with PWS and
OSA from a tertiary pediatric hospital between the years of 2002 and 2012. Pre-
and post-operative sleep studies and sleep disordered breathing symptoms, post
operative VPD assessment by the speech-language pathologist (SLP), and VPD
treatments were evaluated. RESULTS: Eleven patients (five males and six females),
fitting the inclusion criteria, were identified. The age of the patient at the
initial otolaryngologic evaluation ranged from 2 to 9 years. All patients
underwent adenotonsillectomy for sleep disordered breathing. Four patients were
diagnosed with post-operative hypernasality after assessment by a speech-language
pathologist. The hypernasality ranged from mild to moderately severe. Of the four
patients with hypernasality, two were found to have structural issues requiring
surgery (pharyngeal flap). Both of the surgical patients experienced significant
improvement in their VPD after surgery. The remaining two patients were found to
have articulation error patterns that were considered more developmental in
nature and both responded to speech therapy. All patients, except one, had
improvement in their polysomnogram or sleep symptoms after adenotonsillectomy.
However, three patients continue to require continuous positive airway pressure
at night. CONCLUSION: Velopharyngeal dysfunction may occur after
adenotonsillectomy in patients with Prader-Willi Syndrome. Families should be
counseled of this risk and the potential need for operative intervention to
correct it.
PMID- 25130947
TI - Unintentional epidural injection of 88 MUg.kg(-1) of epinephrine.
AB - We report the effects of 88 MUg.kg(-1) of epinephrine (1:10,000) injected into
the caudal epidural space of a 42-week postconceptual age infant. No long-term
neurological or cardiovascular sequelae occurred. Noninvasive cardiac output (CO)
monitoring revealed increased CO, contractility, and stroke volume for about an
hour, accompanied by a reduction in peripheral vascular resistance and a modest
increase in pulse and blood pressure.
PMID- 25130948
TI - Svelte integrated delivery system performance examined through diagnostic
catheter delivery: the SPEED registry.
AB - AIMS: The multi-center SPEED registry evaluated the procedural success and in
hospital clinical outcomes of direct stenting with the Svelte 'all-in-one'
coronary stent Integrated Delivery System (IDS) through diagnostic catheters to
identify the clinical indications for which this approach is appropriately
suited. METHODS & RESULTS: Forty-eight (48) patients with 54 lesions of lengths
<=20 mm and RVD 2.5-3.5 mm were targeted for direct stenting through diagnostic
catheters (4-6F) via radial or femoral approach. Procedural characteristics early
in an investigator's experience (28 lesions) were compared with outcomes
following experience (26 lesions). Procedure, device and strategy success were
realized in 54 (100%), 50 (93%) and 46 (85%) lesions, respectively, with strategy
success significantly related to RVD (P = 0.05), lesion location (P = 0.01), and
diagnostic catheter size (P = 0.05). Significant improvement in crossing and
intervention time and trends toward improvement in device and strategy success,
reductions in procedure and radiation time and contrast use were observed.
CONCLUSIONS: Direct stenting through diagnostic catheters via radial or femoral
approach using the Svelte IDS is feasible and associated with good in-hospital
outcomes. This approach offers the attractive option of assessing lesions via
diagnostic catheter and, depending upon vessel anatomy and lesion morphology,
continuing with ad-hoc interventional treatment using the same diagnostic
catheter. Improvements in strategy success and procedural efficiencies, based on
operator experience, facilitate catheter downsizing and reduce intervention time,
ancillary product use and overall procedure costs. (c) 2014 Wiley Periodicals,
Inc.
PMID- 25130950
TI - Respiratory sinus arrhythmia in Chagas disease.
AB - We applied the respiratory sinus arrhythmia (RSA) quantification algorithm to 24
hour ECG recordings of Chagas disease (ChD) patients with (G1, n=148) and without
left ventricular dysfunction (LVD) (G2, n=33), and in control subjects (G0,
n=28). Both ChD groups displayed a reduced RSA index; G1=299 (144-812); G2=335
(162-667), p=0.011, which was correlated with vagal indexes of heart rate
variability analysis. RSA index is a marker of vagal modulation in ChD patients.
PMID- 25130949
TI - The sympathetic skin response located in the penis as a predictor of the response
to sertraline treatment in patients with primary premature ejaculation.
AB - INTRODUCTION: The pathologic mechanisms of primary premature ejaculation (PPE)
are complex and multifactorial, and hyperactivity of the sympathetic nervous
system is one of the mechanisms. AIM: To examine the effects of sertraline on
sympathetic nervous system activity and assess the predictive value of the
sympathetic skin response located in the penis (PSSR) on the response to
sertraline treatment in PPE patients. METHODS: Sixty-one patients with PPE were
recruited. Each received 50 mg sertraline daily for 8 weeks. Before and after the
experiment, the patients were evaluated for PSSR tests and sexual performance
parameters. Additionally, based on the latency of PSSR, we divided the patients
into a normal PSSR group and an abnormal PSSR group, and compared the sertraline
treatment efficacy between the two groups. MAIN OUTCOME MEASURES: Changes in
intravaginal ejaculation latency time (IELT) and the Chinese premature
ejaculation index-5 (CIPE-5), and the latencies and amplitudes of PSSR after
sertraline treatment. RESULTS: Overall, 58 (95.1%) patients completed the entire
study and were analyzed. After the 8-week sertraline treatment, compared with
those of pretreatment, IELT and CIPE-5 scores were significantly increased (both
P < 0.001), and the amplitudes and latencies of PSSR in the PPE patients were
remarkably decreased and prolonged, respectively (both P < 0.001). In addition,
the changes of the latencies of PSSR were positively correlated with the
increment of IELT (r = 0.375, P = 0.004). The treatment outcome was better in
patients with a baseline abnormal PSSR than in those with a baseline normal PSSR
(P = 0.021). CONCLUSIONS: These results suggest that clinical improvement in
response to sertraline in the PPE patients, at least in part, is mediated through
reducing sympathetic nervous system activity indexed by PSSR. Measurement of the
PSSR appears to provide useful information for predicting treatment responses in
the PPE patients.
PMID- 25130951
TI - Frequency and clinical significance of respiratory isolates of non-tuberculous
mycobacteria in Riyadh, Saudi Arabia.
AB - BACKGROUND AND AIMS: The prevalence of pulmonary non-tuberculous mycobacteria
(NTM) disease is increasing worldwide. The aim of this study was to assess the
frequency and clinical significance of NTM isolated from respiratory specimens at
King Abdul-Aziz Medical City-Riyadh, Saudi Arabia. METHODS: The medical records
of all patients who had at least one respiratory specimen that was positive for
growth of NTM between 2006 and 2012 were retrospectively reviewed. The clinical
significance of the isolates was determined using the diagnostic criteria for NTM
disease published by the American Thoracic Society (ATS). RESULT: A total of 380
respiratory specimens with positive culture for NTM from 142 patients were
identified. Forty patients (28%) had definite pulmonary NTM disease with a mean
(+/- standard deviation) age of 54 +/- 16 years, 58% were male and 50% had had
underlying chronic lung disease. Mycobacterium avium complex (MAC) (n = 19, 48%)
and Mycobacterium abscessus (n = 10, 25%) were the most commonly encountered NTM.
The clinical manifestations of NTM lung disease are non-specific, with symptoms
indistinguishable from pulmonary tuberculosis (TB). The most common radiological
features of NTM lung disease were nodular bronchiectasis (45%) and fibrocavitary
lesions (40%). CONCLUSIONS: Twenty-eight percent of the patients with NTM
isolates met the ATS diagnostic criteria for NTM lung disease. MAC and M.
abscessus were the most encountered NTM isolated species that caused NTM lung
disease in our population, which is a rate similar to many previous studies.
PMID- 25130952
TI - Immunohistochemical staining for BRAF V600E supports the diagnosis of metanephric
adenoma.
PMID- 25130953
TI - Probing the topological properties of the Jackiw-Rebbi model with light.
AB - The Jackiw-Rebbi model describes a one-dimensional Dirac field coupled to a
soliton field and can be equivalently thought of as a model describing a Dirac
field with a spatially dependent mass term. Neglecting the dynamics of the
soliton field, a kink in the background soliton profile yields a topologically
protected zero-energy mode for the field, which in turn leads to charge
fractionalisation. We show here that the model, in the first quantised form, can
be realised in a driven slow-light setup, where photons mimic the Dirac field and
the soliton field can be implemented-and tuned-by adjusting optical parameters
such as the atom-photon detuning. Furthermore, we discuss how the existence of
the zero-mode and its topological stability can be probed naturally by studying
the transmission spectrum. We conclude by analysing the robustness of our
approach against possible experimental errors in engineering the Jackiw-Rebbi
Hamiltonian in this optical setup.
PMID- 25130954
TI - Spectral Doppler interrogation of the patent foramen ovale-a window to left heart
hemodynamics.
AB - Spectral Doppler interrogation of flow across a patent foramen ovale (PFO) allows
recording of the instantaneous pressure gradient between left and right atrium
(RA). The assessment of RA pressure using the size and collapsibility of the
inferior vena cava would thus allow estimation of left atrial (LA) pressure. In
this article, we illustrate the value of spectral Doppler interrogation of flow
across the PFO by transthoracic echocardiography as a novel and simple tool for
the assessment of LA pressure and left cardiac hemodynamics in addition to the
conventional noninvasive parameters.
PMID- 25130955
TI - Extraskeletal myxoid chondrosarcoma with a t(9;16)(q22;p11.2) resulting in a
NR4A3-FUS fusion.
AB - Extraskeletal myxoid chondrosarcoma (EMC) is a rare neoplasm characterized by
rearrangement of NR4A3. A t(9;22)(q22;q12), creating a fusion protein of EWSR1
and NR4A3, has been reported as a unique, recurring translocation in most cases.
Reported variant translocations have resulted in fusion of NR4A3 with three other
genes: TAF15, TCF12, and TFG. We report a case of EMC in a 59-year-old man who
presented with a 6-month history of an enlarging mass in the proximal right
thigh. The karyotype of fresh tissue from tumor taken at incisional biopsy
revealed a t(9;16)(q22;p11.2). There was no evidence of an EWSR1 rearrangement by
dual-color break-apart fluorescence in situ hybridization (FISH). Dual-color FISH
probes revealed fusion of NR4A3 and FUS, a member of the TET family of genes,
which includes EWSR1 and TAF15. Break-apart FISH probe results confirmed
rearrangement of FUS. These findings show that a fusion product of FUS and NR4A3
may be an additional pathway to development of EMC.
PMID- 25130956
TI - Association of sociodemographic factors and prostate-specific antigen (PSA)
testing.
AB - OBJECTIVES: There are conflicting recommendations regarding the use of prostate
specific antigen (PSA) as a screening test. Integral to this debate is an
understanding of who is currently being tested. The purpose of this study was to
provide a detailed account of PSA testing practices in a major Canadian city
(Calgary, Alberta) and to identify variables that may affect access to the PSA
test. DESIGN AND METHODS: PSA test counts were retrieved from Calgary Laboratory
Services' Laboratory Information System from January 1, 2011 to December 31,
2011. A total of 75,914 individual PSA tests were included in our analysis. The
frequency of PSA testing was plotted onto a dissemination area map of Calgary
using ArcGIS software. Associations with sociodemographic variables were tested
using Poisson regression. RESULTS: The median PSA value was 0.93 MUg/L and the
median age at collection was 58 years. Forty-three percent of men aged 60-69
received a PSA test. Visible minority status 'Black' (P=0.0002) and Metis status
(P=0.0075) were associated with lower PSA testing frequencies, while median
household income (P=<0.0001) and university education (P=<0.0001) were associated
with higher PSA testing frequencies. CONCLUSION: There are areas in Calgary which
are significantly over or under tested relative to the mean. The amount of PSA
testing in men <50 years of age is increasing, which is contrary to PSA testing
guidelines.
PMID- 25130957
TI - Evaluation of Beckman Coulter DxI 800 immunoassay system using clinically
oriented performance goals.
AB - OBJECTIVES: We evaluated the analytical performance of 24 immunoassays using the
Beckman Coulter DxI 800 immunoassay systems at Mayo Clinic, Rochester, MN for
trueness, precision, detection limits, linearity, and consistency (across
instruments and reagent lots). METHODS: Clinically oriented performance goals
were defined using the following methods: trueness-published desirable accuracy
limits, precision-published desirable biologic variation; detection limits - 0.1
percentile of patient test values, linearity - 50% of total error, and
consistency-percentage test values crossing key decision points. Local data were
collected for precision, linearity, and consistency. Data were provided by
Beckman Coulter, Inc. for trueness and detection limits. RESULTS: All evaluated
assays except total thyroxine were within the proposed goals for trueness. Most
of the assays met the proposed goals for precision (86% of intra-assay results
and 75% of inter-assay results). Five assays had more than 15% of the test
results below the minimum detection limits. Carcinoembryonic antigen, total
thyroxine and free triiodothyronine exceeded the proposed goals of +/-6.3%, +/-5%
and +/-5.7% for dilution linearity. All evaluated assays were within the proposed
goals for instrument consistency. Lot-to-lot consistency results for cortisol,
ferritin and total thyroxine exceeded the proposed goals of 3.3%, 11.4% and 7% at
one medical decision level, while vitamin B12 exceeded the proposed goals of 5.2%
and 3.8% at two decision levels. CONCLUSIONS: The Beckman Coulter DxI 800
immunoassay system meets most of these proposed goals, even though these
clinically focused performance goals represent relatively stringent limits.
PMID- 25130958
TI - Biological variation of the osmolality and the osmolal gap.
PMID- 25130959
TI - Validating laboratory results in a national observational cohort study without
field centers: the Reasons for Geographic and Racial Differences in Stroke
cohort.
AB - OBJECTIVES: The REasons for Geographic and Racial Differences in Stroke (REGARDS)
study is a prospective cohort of 30,239 Americans in the contiguous United
States; the first of this scale to use home visits to obtain, process, and ship
biologic samples to a core laboratory. Pre-analytical factors resulting from this
study design may affect the results of some laboratory assays. We investigated
the impact of REGARDS processing on a variety of analytes. DESIGN AND METHODS: In
REGARDS, blood samples were processed in the field by technicians who were
trained on standardized methods for phlebotomy and sample processing. Field
processing included centrifugation using varying non-uniform equipment and
shipping overnight on ice to the University of Vermont, where samples were re
centrifuged for 30,000 *g-minutes and stored at -80 degrees C. We assessed the
effects of REGARDS sample handling by processing split samples from 20 volunteers
using either ideal procedures or simulated REGARDS procedures. Assays for 19
analytes for potential study in REGARDS were then run on both samples and results
compared. RESULTS: Spearman correlation coefficients for analytes measured in
ideal versus REGARDS processed samples ranged from 0.11 to 1.0. Thirteen of 19
analytes were highly correlated (>0.75), but platelet proteins were more
variable. CONCLUSIONS: Simulation of non-optimal field processing and shipment to
a central laboratory showed high variability in analytes released by platelets.
The majority of other analytes produced valid results, but platelet contamination
in REGARDS samples makes measurement of platelet proteins unadvisable in these
samples. Future analytes considered by REGARDS or similar studies should undergo
similar pilot testing.
PMID- 25130961
TI - Plantar pressure characteristics in hallux valgus feet.
AB - Due to the pathoanatomical changes in hallux valgus feet, the plantar flexion
moment of the first metatarsophalangeal joint is reduced. Therefore, load bearing
of the hallux is decreased during push-off. We assessed loading parameters in
hallux valgus feet. Based on dorsal-plantar weight bearing radiographs of 61
feet, the intermetatarsal-, hallux valgus-, distal metatarsal articulation-angle,
and sesamoid position were evaluated. Plantar pressure assessment was performed
with the emed(r) system during level walking. We found negative correlations
between hallux valgus angle and peak pressure in the great toe (r=-0.301,
p<0.023), the maximum force of the hallux (r=-0.481, p<0.001), and contact time
of the great toe (r=-0.448, p<0.001), and positive correlations for force time
integral (r=0.348, p<0.001), contact area (r=0.307, p<0.020), maximum force
(r=0.430, p<0.001), and peak pressure (r=0.361, p<0.006) of the fifth metatarsal
head. A positive correlation between the sesamoid and the metatarsal subluxation
regarding maximum force (r=0.294, p<0.034), and a negative correlation between
the contact area of the hallux (r=-0.232, p<0.020) was shown. Depending on the
severity, hallux valgus angle, and sesamoid subluxation, load shows significant
lateral transmission in hallux valgus feet.
PMID- 25130960
TI - Is preoperative radiotherapy suitable for all patients with primary soft tissue
sarcoma of the limbs?
AB - AIM: To evaluate the indications and results of preoperative radiotherapy (RT) on
a series of selected patients treated at our institution with curative intent for
a limb sarcoma (STS). PATIENTS AND METHODS: From 05/1993 to 12/2011, 64 STS
patients received preoperative RT. RESULTS: RT was delivered as a "limb salvage
treatment" prior to surgery for the following reasons: as the preferential
induction treatment in 53 patients (83%) or as a second intent (17%) after the
failure of neoadjuvant systemic chemotherapy/isolated limb perfusion. Surgery was
performed after RT in 54 (84%) patients and final limb salvage was performed in
98%. Musculo-cutaneous flap reconstruction was planned upfront in 44% patients,
and 19% had a skin graft. Seven patients (13%) had a postoperative RT boost.
Thirteen (20%) patients had grade (G) 3/4 adverse events, one after RT and 12
after surgery. At a median follow-up of 3.5 years, the 3-year actuarial overall
survival (OS) and distant relapse (DR) rates were 83% and 31%, respectively. Two
patients developed a local relapse and two a local progression (non-operated
patients). In the multivariate analysis (MVA), histological subtype
(leiomyosarcoma) and grade 3 were predictive of poorer survival. Patients with >3
month delay between the start of RT and surgery at our institution had an
increased risk of DR in the MVA. CONCLUSION: Induction RT should be personalised
according to histological subtype, tumour site and risks-benefit ratio of
preoperative radiotherapy and is best managed by a multidisciplinary surgical and
oncology team in a specialist sarcoma centre.
PMID- 25130962
TI - Routine assessment of psychosocial problems after cancer genetic counseling:
results from a randomized controlled trial.
AB - Approximately 70% of counselees undergoing cancer genetic counseling and testing
(CGCT) experience some degree of CGCT-related psychosocial problems. We evaluated
the efficacy of an intervention designed to increase detection and management of
problems 4 weeks after completion of CGCT. In this randomized, controlled trial,
118 participants completed a CGCT-related problem questionnaire prior to an -
audiotaped - telephone session with their counselor 1 month after DNA-test
disclosure. For those randomized to the intervention group (n = 63), a summary of
the questionnaire results was provided to the counselor prior to the telephone
session. Primary outcomes were discussion of the problems, counselors' awareness
of problems, and problem management. Secondary outcomes included self-reported
distress, cancer worries, CGCT-related problems, and satisfaction. Counselors who
received a summary of the questionnaire were more aware of counselees' problems
in only one psychosocial domain (practical issues). No significant differences in
the number of problems discussed, in problem management, or on any of the
secondary outcomes were observed. The prevalence of problems was generally low.
The telephone session, combined with feedback on psychosocial problems, has
minimal impact. The low prevalence of psychosocial problems 1 month post-CGCT
recommends against its use as a routine extension of the CGCT procedure.
PMID- 25130963
TI - [Down-regulated betaIII-tubulin expression can reverse paclitaxel resistance in
A549/taxol cells lines].
AB - BACKGROUND: Chemotherapy drug resistance is the primary causes of death in
patients with pulmonary carcinoma which make tumor recurrence or metastasis. beta
tubulin is the main cell targets of anti-microtubule drug. Increased expression
of betaIII-tubulin has been implicated in non-small cell lung cancer (NSCLC) cell
lines. To explore the relationship among the expression level of betaIII-tubulin
and the sensitivity of A549/Taxolcell lines to Taxol and cell cycles and cell
apoptosis by RNA interference-mediated inhibition of betaIII-tubulin in
A549/Taxol cells. METHODS: Three pairs of siRNA targetd betaIII-tubulin were
designed and prepared, which were transfected into A549/Taxol cells using
LipofectamineTM 2000. We detected the expression of betaIII-tubulin mRNA using
Real-time fluorescence qRT-PCR. Tedhen we selected the most efficient siRNA by
the expression of betaIII-tubulin mRNA in transfected group. betaIII-tubulin
protein level were mesured by Western blot. The taxol sensitivity in transfected
group were evaluated by MTT assay. And the cell apoptosis and cell cycles were
determined by flow cytometry. RESULTS: betaIII-tubulin mRNA levels in A549/Taxol
cells were significantly decreased in transfected grop by Real-time qRT-PCR than
control groups. And betaIII-tubulin siRNA-1 sequence showed the highest
transfection efficiency, which was (87.73+/-4.87)% (P<0.01); Western blot results
showed that the expressional level of BIII tublin protein was significantly down
reulated in the transfectant cells than thant in the control cells. By MTT assay,
we showed that the inhibition ratio of Taxol to A549/Taxol cells transfeced was
higher than that of control group (51.77+/-4.60)% (P<0.01). The early apoptosis
rate of A549/Taxol cells in transfected group were significantly higher than that
of control group (P<0.01); G2-M content in taxol group obviously increased than
untreated samples by the cell cycle (P<0.05). CONCLUSIONS: betaIII-tubulin down
regulated significantly sensitized NSCLC A549/Taxol cells to Paclitaxel.
PMID- 25130964
TI - [Multi-factor retrospective study in 91 small cell lung cancer patients].
AB - BACKGROUND: Small cell lung cancer accounts for about 15%-25% of lung cancer,
although the new chemotherapy drugs and radiation technology are continuously
progressing, but the prognosis is still poor. To explore the prognostic factor of
small cell lung cancer (SCLC), we study the correlation between effect, prognosis
and TNM stage, various treatment mode. METHODS: We collected 91 Limited-disease
SCLC patients' data From 2006 to 2012. The data were reviewed retrospectively and
restaged as I, II, IIIa and IIIb stage groups according to the clinical staging
in the seventh edition of the tumor. We compare the progression-free survival
(FPS) and overall survival (OS). Survival analysis was evaluated by Kaplan-Meier
and multivariate analysis was performed by Cox proportional hazards model.
RESULTS: In the whole group, patients achieved complete response and partial
response, exhibited an RR of 93.4%. The median PFS was 14.25 months of which,
22.03 months in patients in stage I, 15.97 months in stage II, 11.99 months in
stage IIIa and 10.5 months in stage IIIb (P<0.05). The median overall survival
(OS) was 19.56 months of which, 33.38 months in patients in stage I, 22.07 months
in stage II, 16.0 months in stage IIIa and 15.52 months in stage IIIb (P<0.05).
Patients of stage IIIa and IIIb have longer survival time in earlier radiation
groups then that of later radiation groups. Univariate analysis indicate stage of
TNM, the pattern of radiation therapy and chemotherapy cycles before radiation
therapy were significantly related to the survival in SCLC. Multivariate analysis
showed that stage of TNM, ECOG (Eastern Cooperative Oncology Group) performance
status, pattern of radiation therapy and cycle numbers of chemotherapy before
radiation were factors correlated with survival. CONCLUSIONS: The stage of TNM
may become beneficial prognostic factors in the treatment of LD-SCLC. The time of
radiation therapy in stage IIIa and IIIb is of worth further investigation.
PMID- 25130965
TI - [Postoperative complications of bilobectomy compared with lobectomy in the right
lung of non-small cell lung cancer patients].
AB - BACKGROUND: The mismatch between pleural space and remnant lung after bilobectomy
has been considered as the main reason for the high incidence of postoperative
complications in non-small cell lung cancer (NSCLC) patients. The aim of this
study is to analyze the differences in postoperative complications between
bilobectomy and lobectomy in the right lung of NSCLC patients. METHODS: This
study included 528 NSCLC patients who underwent right pulmonary lobectomy. A
total of 352 cases that underwent upper or lower right lobectomy (108 upper and
244 lower) were the control group, and 176 cases that underwent bilobectomy (57
upper and middle and 119 lower and middle) were the observation group. A
retrospective case-control study was performed on a series of matched NSCLC
patients. Cases and controls were matched by age, ppoFEV1%, LEVF%, operation
method, cardiac comorbidity, type of postoperative management, and pathological
type at a ratio of 1:2. The prevalence of 30-day death, occurrence of cardiac
respiratory complications (hospital-acquired pneumonia, low oxygen concentration,
pulmonary embolism, cerebral apoplexy, arrhythmia, myocardial ischemia or
infarction, and cardiac insufficiency) and occurrence of space-related
complications (atelectasis, air leak more than 5 days, and pneumothorax) were
compared between the bilobectomy and lobectomy groups. RESULTS: The prevalence of
30-day death was 3.4% (6/176) in the bilobectomy group and 2.3% (8/352) in the
lobectomy group. No statistical significance was observed between the two groups.
The cardiac-respiratory complication rate in bilobectomy group (23.8%; 42/176)
was higher than that in lobectomy group (10.7%; 38/352). The cardiac-respiratory
complication rate of the lower and middle pulmonary lobectomy patients in the
bilobectomy group (26.5%; 31/119) was significantly higher than that in the lower
pulmonary lobectomy patients (4.9%; 12/244). The space-related complications in
bilobectomy group and lobectomy group were 20.4% (36/176) and 17.3% (61/352),
respectively. No statistically significant difference between the two groups was
observed. CONCLUSIONS: The postoperative cardiac-respiratory complications of
NSCLC patients with right bilobectomy are higher than those of the right
lobectomy patients, but the prevalence of 30-day death and space-related
complication was not statistically different between the two groups.
PMID- 25130966
TI - [A meta-analysis of Association between MGMT gene promoter methylation and non
small cell lung cancer].
AB - BACKGROUND: DNA promoter methylation of the tumor suppressor genes was one of the
key mechanism for gene silence. The aim of this study is to investigate the
difference of MGMT gene promoter methylation rate in tumor tissue and autologous
controls (serum, normal lung tissue and bronchial lavage fluid) in patients with
non-small cell lung cancer (NSCLC). METHODS: The databases of Medline, EMBSE,
CNKI and Wanfang were searched for selection of published articles of MGMT gene
promoter methylation and non-small cell lung carcinoma risk. The pooled odds
ratio (OR) and percentage of MGMT for lung cancer tissue of NSCLC patients
compared with normal lung tissue, plasma and the bronchial lavage fluid were
pooled. RESULTS: 15 articles of association between MGMT gene promoter
methylation and non small cell lung carcinoma risk were included in this meta
analysis. The combined results demonstrated the methylation rate of MGMT in NSCLC
cancer tissue was 38% (95%CI: 23%-53%). For normal lung tissue, plasma and the
bronchial lavage fluid were 16% (95%CI: 5%-27%), 23% (95%CI: 10%-34%) and 39%
(95%CI: 23%-55%) respectively. The OR in cancer tissue was much higher than that
in normal lung tissue and plasma odds ratio (OR) 3.98 (95%CI: 2.71-5.84, P<0.05)
and OR 1.88 (95%CI: 1.16-3.05, P<0.05), but not in bronchial lavage fluid OR 2.05
(95%CI: 0.88-4.78, P>0.05). CONCLUSIONS: Mehtylation rate in MGMT gene promoter
of cancer tissue in NSCLC patients was much higher than that in normal lung
tissue and plasma, which showed a close association between NSCLC cancer and MGMT
gene promoter methylation.
PMID- 25130967
TI - [A comparison of direct sequencing and ARMS assay performance in EGFR mutation
analysis of non-small cell lung cancer patients].
AB - BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors are mainly used
for the targeted therapy of non-small cell lung cancer (NSCLC). Therefore, EGFR
mutations should be detected to treat lung cancer. The aim of this study is to
determine the detection rate of NSCLC in patients with EGFR gene mutations by
conducting direct sequencing and ARMS assay. METHODS: A total of 451 patients who
were diagnosed with NSCLC between April 2012 and June 2013 participated in this
study. Gene mutation was detected in the exon of EGFR 18 to 21 by direct
sequencing and ARMS assay. RESULTS: All of the 451 cases of NSCLC were subjected
to direct sequencing and ARMS assay. Using both techniques, we detected the same
EGFR mutation in 127 cases and different EGFR mutations in 5 cases, but no
mutations were detected in 186 cases. In direct sequencing alone, EGFR mutation
was detected in 50 cases. In ARMS assay alone, EGFR mutation was detected in 83
cases. The mutation rates of direct sequencing and ARMS assay were 40.4% and
47.7%, respectively. Therefore, the mutation detection rate of ARMS assay was
significantly higher than that of direct sequencing (P<0.001). In 204 paraffin
tissue samples of NSCLC, the mutation detection rate of ARMS assay (59.80%) was
significantly higher than that of direct sequencing (41.67%; P<0.001). By
comparison, the mutation detection rates of ARMS assay (39.58%) and direct
sequencing (38.33%) showed no significant difference (P=0.083) when 240 fresh
tissue samples of NSCLC were used. CONCLUSIONS: Direct sequencing and ARMS assay
exhibited similar efficacy in detecting EGFR mutations. Despite its high
operational costs, ARMS assay was more sensitive and more convenient than direct
sequencing, particularly when a small number of tissues were used. By comparison,
direct sequencing could detect mutations that were not detected by ARMS assay.
Therefore, the combination of direct sequencing and ARMS assay could provide more
reliable and comprehensive test results than the lone application of each
technique.
PMID- 25130968
TI - [Association of genetic polymorphisms in IL-6 and IL-1beta gene with risk of lung
cancer in female non-smokers].
AB - BACKGROUND: Interleukin-6 (IL-6) and interleukin-1beta (IL-1beta), known as
multifunctional cytokines with high biological activity, play an important role
in physiological and pathological responses such as inflammation, immune response
and even tumors. There have been multiple polymorphism loci found in IL-6 gene
and IL-1beta gene. The aim of this study is to investigate the relationship
between IL-6-643 (C/G) and IL-1beta-31 (C/T) polymorphisms and lung cancer risk
among female non-smokers and explore the interaction effects on lung cancer risk
between this two polymorphisms and potential risk factors such as cooking oil
fumes exposure and history of tuberculosis. METHODS: We performed a case-control
study using 363 female lung cancer patients as cases and 370 healthy volunteers
as controls. Genomic DNA was extracted from peripheral blood samples using
classical phenol chloroform method. The genotyping of IL-6-634 or IL-1beta-31
polymorphisms was performed using Taqman real time PCR technique by ABI7500. Two
sided chi2 test was used to compare the distribution of the genotypes and risk
factors between cases and controls. Unconditional Logistic regression analysis
was performed to calculate the odds ratios (ORs) with 95% confidence intervals
(CIs) for estimating the association between certain genotypes and lung cancer
and exploring the interaction of risk factors and genetic polymorphisms. RESULTS:
The risk of lung cancer was significantly higher in those with IL-6-634 CG
genotype than those with CC genotype (OR=1.61, 95%CI: 1.19-2.19, P=0.002). The CG
or GG genotype carriers had an elevated risk of lung cancer than CC genotype
carriers (OR=1.48, 95%CI: 1.10-1.98, P=0.01). No significant association was
observed between IL-1beta-31 gene polymorphism and lung cancer risk. Compared
with IL-6-634 CC genotype carriers with no cooking oil fumes exposure, a
significant higher risk was found in individuals who were CG or GG genotype
carriers with exposure to cooking oil fumes (OR=2.45, 95%CI: 1.54-3.90). Compared
with IL-6-634 CC genotype carriers with no history of tuberculosis, a significant
elevated risk was found in individuals who were CG or GG genotype carriers with
history of tuberculosis (OR=2.44, 95%CI: 1.05-5.66). CONCLUSIONS: Our results
indicated that IL-6-634 polymorphism was associated with the risk of lung cancer
risk in female non-smokers. Individuals with both IL-6-634 CG or GG genotype and
exposure to cooking oil fumes had a higher risk of lung cancer. Also individuals
with both IL-6-634 CG or GG genotype and history of tuberculosis had an elevated
risk of lung cancer.
PMID- 25130969
TI - [Research status on molecular targeted therapy for squamous-cell lung cancer].
AB - Lung cancer is one of the world's highest morbidity and mortality disease in
malignant tumors currently. Squamous-cell lung cancer (SQCLC) is one of the most
prevalent subtypes of lung cancer worldwide, after surgery, radiotherapy,
chemotherapy and other comprehensive treatment, its 5-year survival rate is still
below 15%. The current molecular targeted therapy plays an important role in the
treatment of SQCLC, an urgent need to be more in-depth study. SQCLC molecular
targeted therapy mainly epidermal growth factor receptor (EGFR), phosphoin-3
kinase catalytic alpha polypeptide (PIK3CA), fibroblast growth factor receptor 1
(FGFR1), discoidin domain receptor 2 (DDR2), phosphatase and tensin homolog
deleted on chromosome ten (PTEN), BRAF, MET, insulin-like growth factor 1
receptor (IGF-1R) and other as the target of the drug, some targeted drugs are
being developed, and some targeted drugs have entered clinical trials. In recent
years, with studies molecular targeted therapy in SQCLC, analysis of the
development and trgeted therapy achieved substantial progress in improving the
survival rate of SQCLC, and other research to improve the quality of life, make
is possible to individualized targeted therapy of SQCLC.
PMID- 25130970
TI - [Dysregulation of HGF/c-Met signal pathway and their targeting drugs in lung
cancer].
AB - C-MET is a coding product of proto oncogene c-MET, hepatocyte growth factor (HGF)
receptor with tyrosine kinase activity. The abnormal expression of c-Met gene is
correlated with the tumorigenesis and development of lung cancer. Once the
tyrosine kinase is activated by the interaction between the HGF ligand and the TK
receptor, and the activated kinase will promote the cell proliferation,
angiogenesis, invasion and metastasis of different tumors, as well as lung
cancer. The targeted therapy to HGF/c-Met signal pathway is a new highlight in
the treatments of lung cancer. In this review, we will discuss the dysregulation
of HGF/c-Met signal pathway in lung cancer and the new progress for the targeted
drugs to this pathway.
PMID- 25130972
TI - The response regulator BcSkn7 is required for vegetative differentiation and
adaptation to oxidative and osmotic stresses in Botrytis cinerea.
AB - The high-osmolarity glycerol pathway plays an important role in the responses of
fungi to various environmental stresses. Saccharomyces cerevisiae Skn7 is a
response regulator in the high-osmolarity glycerol pathway, which regulates the
oxidative stress response, cell cycle and cell wall biosynthesis. In this study,
we characterized an Skn7 orthologue BcSkn7 in Botrytis cinerea. BcSKN7 can partly
restore the growth defects of S. cerevisiae SKN7 mutant and vice versa. The
BcSKN7 mutant (DeltaBcSkn7-1) revealed increased sensitivity to ionic osmotic and
oxidative stresses and to ergosterol biosynthesis inhibitors. In addition,
DeltaBcSkn7-1 was also impaired dramatically in conidiation and sclerotial
formation. Western blot analysis showed that BcSkn7 positively regulated the
phosphorylation of BcSak1 (the orthologue of S. cerevisiae Hog1) under osmotic
stress, indicating that BcSkn7 is associated with the high-osmolarity glycerol
pathway in B. cinerea. In contrast with BcSak1, BcSkn7 is not involved in the
regulation of B. cinerea virulence. All of the phenotypic defects of DeltaBcSkn7
1 are restored by genetic complementation of the mutant with the wild-type
BcSKN7. The results of this study indicate that BcSkn7 plays an important role in
the regulation of vegetative differentiation and in the response to various
stresses in B. cinerea.
PMID- 25130973
TI - Recent advances in the evaluation of the oxygen transfer rate in oak barrels.
AB - The entry of atmospheric oxygen into wine barrels is a desirable characteristic
of the wine aging process. The oxygen transfer rate regulates changes in wine
affecting aging rates because some barrels may undergo a greater wine
oxygenation. This study measured the transfer rate and oxygen distribution within
a barrel. The analysis confirmed the presence of a dissolved oxygen concentration
gradient in the liquid, with greater concentrations near the bung. The study of
the transfer rate of oxygen over time, in 12 barrels of different types, showed
that wetting wood reduces oxygen diffusion and the oxygen transfer rate (OTR).
These results are the first to determine the kinetics of oxygen entry into wine
barrels and can be used to quantify the annual rate of oxygen entry into wine
barrels.
PMID- 25130971
TI - [Effect of PI3K/AKT pathway on cisplatin resistance in non-small cell lung
cancer].
AB - Accumulating evidences indicate that aberrant activation of PI3K/AKT pathway in
non-small cell lung cancer plays a vital role in tumor cell
proliferation,apoptosis, and survival including drug resistance. Cisplatin as
first-line chemotherapy are in widespread clinical use in patients with non-small
cell lung cancer, however, the development of cisplatin resistance significantly
impedes its clinic efficacy. Cisplatin resistance is a complicated process that
various mechanisms participating in to interact, of which PI3K/AKT pathway
keeping sustained activated is one of the most important reasons. This article
reviewed the progress of research on the relationship between PI3K/AKT pathway
and cisplatin resistance.
PMID- 25130974
TI - Bridging the gap between metabolic liver processes and functional tissue
structure by integrated spatiotemporal modeling applied to hepatic ammonia
detoxification.
PMID- 25130975
TI - Neurophysiological evidence for generalized sensory neuronopathy in cerebellar
ataxia with neuropathy and bilateral vestibular areflexia syndrome.
AB - INTRODUCTION: Cerebellar ataxia with neuropathy and bilateral vestibular
areflexia syndrome (CANVAS) is a recently described multisystem ataxia defined by
the presence of cerebellar ataxia, bilateral vestibulopathy, and a somatosensory
deficit. The characteristic clinical sign is an abnormal visually enhanced
vestibuloocular reflex. The somatosensory deficit contributes to a significant
level of disability in CANVAS. METHODS: This study was a neurophysiological
investigation of 14 patients with CANVAS. RESULTS: Findings revealed uniformly
absent sensory nerve action potentials in all limbs, abnormal blink reflexes in
13 of 14 patients, and abnormal masseter reflexes in 6 of 11 patients. Tibial H
reflexes were absent in 11 of 14 patients. Somatosensory evoked potentials were
abnormal in 10 of the 11 patients tested, and brainstem auditory evoked responses
were abnormal in 3 of 8. Cutaneous silent period responses were abnormal in 7 of
14 patients. CONCLUSIONS: We suggest that a sensory neuronopathy should be sought
in cerebellar and/or vestibular ataxias, particularly where the degree of ataxia
is out of proportion to the clinically identified cerebellar and/or vestibular
dysfunction.
PMID- 25130977
TI - The electrode-tissue interface: the revolutionary role of steroid-elution.
AB - The electrode-tissue interface is that area lying between the cathode of a low
voltage implantable pacemaker or cardioverter-defibrillator (ICD) lead and the
endocardium or epi-myocardium of the cardiac chamber being paced. The electrical
stimulus that is delivered to this interface is responsible for myocyte
depolarization with consequent cardiac contraction. The process by which this
occurs is reasonably well understood and any explanation requires a basic
understanding of the physics and cellular electrophysiology of pacing. The
effective and efficient delivery of electrical energy to the myocardium via the
lead is dependent on many factors to be discussed in this review. However,
despite numerous evolutionary changes occurring in the cathode's material,
design, and surface configuration, it was not until the incorporation of steroid
elution to the electrode-tissue interface that reliable and significantly low
stimulation threshold cardiac pacing became possible.
PMID- 25130978
TI - The economic burden of pneumonia and meningitis among children less than five
years old in Hanoi, Vietnam.
AB - OBJECTIVE: To estimate the average treatment costs of pneumonia and meningitis
among children under five years of age in a tertiary hospital in Hanoi, Vietnam
from societal, health sector and household perspectives. METHODS: We used a cost
of-illness approach to identify cost categories to be included for different
perspectives. A prospective survey was conducted among eligible patients to get
detailed personal costing items. RESULTS: From the perspective of the health
sector, the mean costs for treating a case of pneumonia and meningitis were USD
180 and USD 300, respectively. From the household's perspective, the average
treatment costs were USD 272 for pneumonia and USD 534 for meningitis. When also
including indirect costs, the average total treatment costs from the societal
perspective were USD 318 for pneumonia and USD 727 for meningitis. CONCLUSION:
The study contributed to limited evidence on the high treatment costs of
pneumonia and meningitis to the Vietnamese society, which is useful for a cost
effectiveness analysis of Haemophilus influenzae type b vaccine or other relevant
disease preventions. It also indicated a need to re-evaluate the health insurance
policy for children under 6 years old, so that the unnecessarily high out-of
pocket costs of these diseases are reduced.
PMID- 25130979
TI - Morphological alterations in the synganglion and integument of Rhipicephalus
sanguineus ticks exposed to aqueous extracts of neem leaves (Azadirachta indica
A. JUSS).
AB - Currently, the necessity of controlling infestation by ticks, especially by
Rhipicephalus sanguineus, has led researchers and public health managers around
the world to search for new and more efficient control methods. This way, we can
highlight neem (Azadirachta indica A. Juss) leaf, bark, and seed extracts, which
have been very effective on tick control, and moreover causing less damage to the
environment and to the host. This study showed the potential of neem as a control
method for R. sanguineus through morphological and morphometric evaluation of the
integument and synganglion of females, in semiengorged stage. To attain this,
routine techniques of optical microscopy, scanning electron microscopy and
morphometry of the cuticle and subcuticle of the integument were applied.
Expressive morphological alterations were observed in both organs, presenting a
dose-dependent effect. Integument epithelial cells and nerve cells of the
synganglion showed signs of cell vacuolation, dilated intercellular boundaries,
and cellular disorganization, alterations not previously reported in studies with
neem. In addition, variations in subcuticle thickness were also observed. In
general, the effects of neem are multiple, and affect the morphology and
physiology of target animals in various ways. The results presented in this work
are the first evidence of its effects in the coating and nervous system of ticks,
thus allowing an indication of neem aqueous extracts as a potential control
method of the brown dog tick and opening new perspectives on acaricide use.
PMID- 25130980
TI - Cryptocoryne spiralis, a substitute of Aconitum heterophyllum in the treatment of
diarrhoea.
AB - OBJECTIVE: To scientifically validate the traditional substitution of roots of
highly expensive Aconitum heterophyllum (AH) with rhizomes of Cryptocoryne
spiralis (CS) in the treatment of diarrhoea. METHODS: Different fractions from
root/rhizome extract of both the plant were subjected to faecal excretion rate
and castor oil-induced diarrhoea models. Further, bioactive fractions from both
plants, i.e. chloroform (CAH) from AH at 50 mg/kg p.o. and ethyl acetate (EACS)
from CS at 100 mg/kg p.o., were examined for small intestinal transit, intestinal
fluid accumulation and PGE2 -induced enteropooling models in rats. Biochemical
estimations and Na(+) and K(+) concentration in intestinal fluid were also
determined along with antibacterial studies. Phytochemical standardisation of AH
and CS was performed by quantifying aconitine for the former and stigmasterol for
the latter using HPLC. KEY FINDINGS: CAH and EACS illustrated a significant
reduction in faecal output rate and demonstrated a protection of 63.068% at CAH
50 and 59.090% at EACS 100 mg/kg p.o. in castor oil-induced diarrhoea model. The
fractions also persuaded promising effects in all the other models, restored
alterations in biochemical parameters and showed potential antibacterial
activity. CONCLUSION: The antidiarrhoeal potential of AH and CS may be attributed
to an antimotility and antisecretory type of effect.
PMID- 25130981
TI - The stroke 'Act FAST' campaign: remembered but not understood?
AB - BACKGROUND: The stroke awareness raising campaign 'Act FAST' (Face, Arms, Speech:
Time to call Emergency Medical Services) has been rolled out in multiple waves in
England, but impact on stroke recognition and response remains unclear. PURPOSE:
The purpose of this study was to test whether providing knowledge of the FAST
acronym through a standard Act FAST campaign leaflet increases accurate
recognition and response in stroke-based scenario measures. METHODS: This is a
population-based, cross-sectional survey of adults in Newcastle upon Tyne, UK,
sampled using the electoral register, with individuals randomized to receive a
questionnaire and Act FAST leaflet (n = 2500) or a questionnaire only (n = 2500)
in 2012. Campaign message retention, stroke recognition, and response measured
through 16 scenario-based vignettes were assessed. Data were analyzed in 2013.
RESULTS: Questionnaire return rate was 32.3% (n = 1615). No differences were
found between the leaflet and no-leaflet groups in return rate or demographics.
Participants who received a leaflet showed better campaign recall (75.7% vs.
68.2%, P = 0.003) and recalled more FAST mnemonic elements (66.1% vs. 45.3%
elements named correctly, P < 0.001). However, there were no between-group
differences for stroke recognition and response to stroke-based scenarios (P >
0.05). CONCLUSIONS: Despite greater levels of recall of specific 'Act FAST'
elements among those receiving the Act FAST leaflet, there was no impact on
stroke recognition and response measures.
PMID- 25130982
TI - Quantification and probabilistic modeling of CRT obsolescence for the State of
Delaware.
AB - The cessation of production and replacement of cathode ray tube (CRT) displays
with flat screen displays have resulted in the proliferation of CRTs in the
electronic waste (e-waste) recycle stream. However, due to the nature of the
technology and presence of hazardous components such as lead, CRTs are the most
challenging of electronic components to recycle. In the State of Delaware it is
due to this challenge and the resulting expense combined with the large
quantities of CRTs in the recycle stream that electronic recyclers now charge to
accept Delaware's e-waste. Therefore it is imperative that the Delaware Solid
Waste Authority (DSWA) understand future quantities of CRTs entering the waste
stream. This study presents the results of an assessment of CRT obsolescence in
the State of Delaware. A prediction model was created utilizing publicized sales
data, a variety of lifespan data as well as historic Delaware CRT collection
rates. Both a deterministic and a probabilistic approach using Monte Carlo
Simulation (MCS) were performed to forecast rates of CRT obsolescence to be
anticipated in the State of Delaware. Results indicate that the peak of CRT
obsolescence in Delaware has already passed, although CRTs are anticipated to
enter the waste stream likely until 2033.
PMID- 25130983
TI - Macrophage induced gelsolin in response to Group B Streptococcus (GBS) infection.
AB - Group B Streptococcus (GBS) has evolved several strategies to avoid host
defences. We have shown that interaction of macrophages with GBS causes
macrophage calpain activation, cytoskeletal disruption and apoptosis,
consequences of intracellular calcium increase induced by membrane permeability
alterations provoked by GBS-beta-haemolysin. Open question remains about what
effect calcium influx has on other calcium-sensing proteins such as gelsolin,
involved in cytoskeleton modulation and apoptosis. Therefore we analysed the
effect of GBS-III-COH31:macrophage interaction on gelsolin expression. Here we
demonstrate that an early macrophage response to GBS-III-COH31 is a very strong
gelsolin increase, which occurs in a time- and infection-ratio-dependent manner.
This is not due to transcriptional events, translation events, protein turnover
alterations, or protein-kinase activation, but to calcium influx, calpain
activation and caspase-3 degradation. In fact, EGTA and PD150606 (calpain
inhibitor) prevented gelsolin increase while BAF (caspase inhibitor) enhanced it.
Since gelsolin increase is induced by highly beta-haemolytic GBS-III-NEM316 and
GBS-V-10/84, but not by weakly beta-haemolytic GBS, or GBS-III-COH31 in
conditions suppressing beta-haemolysin expression/activity and the presence of
dipalmitoylphosphatidylcholine (beta-haemolysin inhibitor), GBS-beta-haemolysin
is solely responsible for gelsolin increase causing, through membrane
permeability defects, calcium influx and calpain activation. Early gelsolin
increase could represent a macrophage response to antagonize apoptosis since
gelsolin knockdown increases macrophage susceptibility to GBS-induced apoptosis.
This response seems to be GBS specific because macrophage apoptosis by
Staurosporine or Cycloeximide does not induce gelsolin.
PMID- 25130976
TI - Etiology, triggers and neurochemical circuits associated with unexpected,
expected, and laboratory-induced panic attacks.
AB - Panic disorder (PD) is a severe anxiety disorder that is characterized by
recurrent panic attacks (PA), which can be unexpected (uPA, i.e., no clear
identifiable trigger) or expected (ePA). Panic typically involves an abrupt
feeling of catastrophic fear or distress accompanied by physiological symptoms
such as palpitations, racing heart, thermal sensations, and sweating. Recurrent
uPA and ePA can also lead to agoraphobia, where subjects with PD avoid situations
that were associated with PA. Here we will review recent developments in our
understanding of PD, which includes discussions on: symptoms and signs associated
with uPA and ePAs; Diagnosis of PD and the new DSM-V; biological etiology such as
heritability and gene*environment and gene*hormonal development interactions;
comparisons between laboratory and naturally occurring uPAs and ePAs;
neurochemical systems that are associated with clinical PAs (e.g. gene
associations; targets for triggering or treating PAs), adaptive fear and panic
response concepts in the context of new NIH RDoc approach; and finally strengths
and weaknesses of translational animal models of adaptive and pathological panic
states.
PMID- 25130984
TI - Near-IR-triggered, remote-controlled release of metal ions: a novel strategy for
caged ions.
AB - A ligand incorporating a dithioethenyl moiety is cleaved into fragments which
have a lower metal-ion affinity upon irradiation with low-energy red/near-IR
light. The cleavage is a result of singlet oxygen generation which occurs on
excitation of the photosensitizer modules. The method has many tunable factors
that could make it a satisfactory caging strategy for metal ions.
PMID- 25130985
TI - Laparoscopic hepatectomy is theoretically better than open hepatectomy: preparing
for the 2nd International Consensus Conference on Laparoscopic Liver Resection.
AB - Six years have passed since the first International Consensus Conference on
Laparoscopic Liver Resection was held. This comparatively new surgical technique
has evolved since then and is rapidly being adopted worldwide. We compared the
theoretical differences between open and laparoscopic liver resection, using
right hepatectomy as an example. We also searched the Cochrane Library using the
keyword "laparoscopic liver resection." The papers retrieved through the search
were reviewed, categorized, and applied to the clinical questions that will be
discussed at the 2nd Consensus Conference. The laparoscopic hepatectomy procedure
is more difficult to master than the open hepatectomy procedure because of the
movement restrictions imposed upon us when we operate from outside the body
cavity. However, good visibility of the operative field around the liver, which
is located beneath the costal arch, and the magnifying provide for neat
transection of the hepatic parenchyma. Another theoretical advantage is that
pneumoperitoneum pressure reduces hemorrhage from the hepatic vein. The
literature search turned up 67 papers, 23 of which we excluded, leaving only 44.
Two randomized controlled trials (RCTs) are underway, but their results are yet
to be published. Most of the studies (n = 15) concerned short-term results, with
some addressing long-term results (n = 7), cost (n = 6), energy devices (n = 4),
and so on. Laparoscopic hepatectomy is theoretically superior to open hepatectomy
in terms of good visibility of the operative field due to the magnifying effect
and reduced hemorrhage from the hepatic vein due to pneumoperitoneum pressure.
However, there is as yet no evidence from previous studies to back this up in
terms of short-term and long-term results. The 2nd International Consensus
Conference on Laparoscopic Liver Resection will arrive at a consensus on the
basis of the best available evidence, with video presentations focusing on
surgical techniques and the publication of guidelines for the standardization of
procedures based on the experience of experts.
PMID- 25130986
TI - Surgical management of thymic epithelial tumors in children: lessons from the
French Society of Pediatric Oncology and review of the literature.
AB - PURPOSE: We report the results of a French multicenter retrospective study based
on a period of more than 30 years and a review of the literature in order to more
clearly define the surgical approach and specific pediatric risk factors.
METHODS: Clinical data of children comprising all histologic subtypes of thymic
epithelial tumors (TET) treated between 1979 and 2009 in French pediatric
oncology centers were retrospectively analyzed and discussed in the light of a
review of all pediatric cases reported in the literature. RESULTS: Nine cases
were identified, corresponding to five females and four males with a median age
of 13 years (range: 7.5-17). Histologic subtypes were type AB (n = 1), type B (n
= 5) and type C (n = 3). Treatment consisted of tumor resection (4 R0, 4 R1, 1
R2) via right anterior thoracotomy, posterolateral thoracotomy, left
thoracoscopy, sternotomy and cervicosternotomy, and/or chemotherapy, mainly
cyclophosphamide-doxorubicin-cisplatin (CAP; n = 5), and/or radiotherapy (n = 4).
Two patients with TET type C died. All other patients are alive with a median
follow-up of 4 years (range: 1.5-20). Review of a total of 93 pediatric cases
reported in the literature showed statistically significant associations between
less favorable histologic subtypes and male gender (P = 0.012), advanced Masaoka
stage (P < 0.001) and quality of resection (P < 0.001) respectively. CONCLUSIONS:
A review of the literature and our series identified several risk factors to take
into account in the therapeutically decision. Complete resection through a
sternotomy is highly recommended.
PMID- 25130987
TI - Effect O6-guanine alkylation on DNA flexibility studied by comparative molecular
dynamics simulations.
AB - Alkylation of guanine at the O6 atom is a highly mutagenic DNA lesion because it
alters the coding specificity of the base causing G:C to A:T transversion
mutations. Specific DNA repair enzymes, e.g. O(6)-alkylguanin-DNA-Transferases
(AGT), recognize and repair such damage after looping out the damaged base to
transfer it into the enzyme active site. The exact mechanism how the repair
enzyme identifies a damaged site within a large surplus of undamaged DNA is not
fully understood. The O(6)-alkylation of guanine may change the deformability of
DNA which may facilitate the initial binding of a repair enzyme at the damaged
site. In order to characterize the effect of O(6)-methyl-guanine (O(6)-MeG)
containing base pairs on the DNA deformability extensive comparative molecular
dynamics (MD) simulations on duplex DNA with central G:C, O(6)-MeG:C or O(6)
MeG:T base pairs were performed. The simulations indicate significant differences
in the helical deformability due to the presence of O(6)-MeG compared to regular
undamaged DNA. This includes enhanced base pair opening, shear and stagger
motions and alterations in the backbone fine structure caused in part by
transient rupture of the base pairing at the damaged site and transient insertion
of water molecules. It is likely that the increased opening motions of O(6)-MeG:C
or O(6)-MeG:T base pairs play a decisive role for the induced fit recognition or
for the looping out of the damaged base by repair enzymes.
PMID- 25130988
TI - Paradoxical findings in direct antiglobulin test and classification of
agglutinating autoantibodies using eluates and monospecific anti-human globulin
sera.
AB - BACKGROUND AND OBJECTIVES: Agglutinating autoantibodies are rarely the cause of
autoimmune haemolytic anaemia (AIHA) of warm type. These antibodies can be
difficult to classify, and serological testing may result in confusion. Here, we
describe the occurrence of paradoxical results in direct antiglobulin test (DAT)
and a simple technique for the characterization of such antibodies. MATERIALS AND
METHODS: Seven patients with AIHA were included in this study. Serological
testing was performed using standard techniques. Classification of autoantibodies
was performed by preincubation of the eluates from patients' red blood cells
(RBCs) with monospecific anti-human globulin sera (mAHG). RESULTS: Strong
autoagglutination of patients' RBCs was observed in six of seven cases, with the
identification of panagglutinating serum antibodies in three patients. Initially,
cold agglutinins with high thermal amplitude were suggested in four patients, and
IgM warm autoantibodies were suggested in the remaining three patients. However,
inhibition of the eluates revealed autoantibodies of IgA class in two patients,
of IgM class in three other cases and of IgG class in two patients. The results
of DAT were confusing due to paradoxical effects of mAHG and/or strong
autoagglutination. CONCLUSION: Strongly agglutinating autoantibodies can be a
source of confusion and can be classified by inhibition experiments using eluates
and monospecific antibodies.
PMID- 25130989
TI - GMM logistic regression models for longitudinal data with time-dependent
covariates and extended classifications.
AB - When analyzing longitudinal data, it is essential to account both for the
correlation inherent from the repeated measures of the responses as well as the
correlation realized on account of the feedback created between the responses at
a particular time and the predictors at other times. As such one can analyze
these data using generalized estimating equation with the independent working
correlation. However, because it is essential to include all the appropriate
moment conditions as you solve for the regression coefficients, we explore an
alternative approach using a generalized method of moments for estimating the
coefficients in such data. We develop an approach that makes use of all the valid
moment conditions necessary with each time-dependent and time-independent
covariate. This approach does not assume that feedback is always present over
time, or if present occur at the same degree. Further, we make use of
continuously updating generalized method of moments in obtaining estimates. We
fit the generalized method of moments logistic regression model with time
dependent covariates using SAS PROC IML and also in R. We used p-values adjusted
for multiple correlated tests to determine the appropriate moment conditions for
determining the regression coefficients. We examined two datasets for
illustrative purposes. We looked at re-hospitalization taken from a Medicare
database. We also revisited data regarding the relationship between the body mass
index and future morbidity among children in the Philippines. We conducted a
simulated study to compare the performances of extended classifications.
PMID- 25130990
TI - How accurate is sperm morphology as an indicator of sperm function?
AB - Sperm morphology has been consistently correlated with fertilisation success or
failure. The clinical relevance of the percentage normal spermatozoa has been a
widely discussed topic amongst infertility specialists and scientists. This study
aimed to evaluate the role of sperm morphology as an indicator of additional
sperm functions among 114 andrology referrals. The sperm functions that were
investigated included chromatin packaging quality (CMA3 test (n = 109), zona
induced acrosome reaction (ZIAR test; n = 36), hemizona assay (HZI; n = 36) and
progressive motility (n = 47). Chromatin packaging quality had a negative and
significant (P = 0.0001, r = -0.74) correlation with the percentage normal
spermatozoa, while progressive motility had a significant and positive
correlation (P = 0.0001, 0.59). Accurate sperm morphology scoring as described by
the WHO 2010 manual can therefore be used as an indicator of specific sperm
functions.
PMID- 25130991
TI - Laterally structured ripple and square phases with one and two dimensional
thickness modulations in a model bilayer system.
AB - Molecular dynamics simulations of bilayers in a surfactant/co-surfactant/water
system with explicit solvent molecules show formation of topologically distinct
gel phases depending upon the bilayer composition. At low temperatures, the
bilayers transform from the tilted gel phase, Lbeta', to the one dimensional (1D)
rippled, Pbeta' phase as the surfactant concentration is increased. More
interestingly, we observe a two dimensional (2D) square phase at higher
surfactant concentration which, upon heating, transforms to the gel Lbeta' phase.
The thickness modulations in the 1D rippled and square phases are asymmetric in
two surfactant leaflets and the bilayer thickness varies by a factor of ~2
between maximum and minimum. The 1D ripple consists of a thinner interdigitated
region of smaller extent alternating with a thicker non-interdigitated region.
The 2D ripple phase is made up of two superimposed square lattices of maximum and
minimum thicknesses with molecules of high tilt forming a square lattice
translated from the lattice formed with the thickness minima. Using Voronoi
diagrams we analyze the intricate interplay between the area-per-head-group,
height modulations and chain tilt for the different ripple symmetries. Our
simulations indicate that composition plays an important role in controlling the
formation of low temperature gel phase symmetries and rippling accommodates the
increased area-per-head-group of the surfactant molecules.
PMID- 25130993
TI - Role of bisphosphonates in non-metastatic prostate cancer.
PMID- 25130994
TI - Fertility preservation for girls and young women with cancer: population-based
validation of criteria for ovarian tissue cryopreservation.
AB - BACKGROUND: Ovarian tissue cryopreservation with later reimplantation has been
shown to preserve fertility in adult women, but this approach remains unproven
and experimental in children and adolescents. We aimed to assess the use of the
Edinburgh selection criteria for ovarian tissue cryopreservation in girls and
young women with cancer to determine whether we are offering this invasive
procedure to the patients who are most at risk of premature ovarian
insufficiency. METHODS: Cryopreservation of ovarian tissue has been selectively
offered to girls and young women with cancer who met the Edinburgh selection
criteria since 1996. Between Jan 1, 1996, and June 30, 2012, 410 female patients
younger than 18 years at diagnosis were treated for cancer (including leukaemia
and brain tumours) at the Edinburgh Children's Cancer Centre, which serves the
whole South East of Scotland region. We determined the ovarian status of these
patients from review of clinical records and classified them as having premature
ovarian insufficiency or not, or as unable to be determined. Patients younger
than 12 years at time of data cutoff (Jan 31, 2013) were excluded from the
analysis. FINDINGS: 34 (8%) of the 410 patients met the Edinburgh selection
criteria and were offered ovarian tissue cryopreservation before starting cancer
treatment. 13 patients declined the procedure and 21 consented, and the procedure
was completed successfully in 20 patients. Of the 20 patients who had ovarian
tissue successfully cryopreserved, 14 were available for assessment of ovarian
function. Of the 13 patients who had declined the procedure, six were available
for assessment of ovarian function. Median age at the time of follow-up for the
20 assessable patients was 16.9 years (IQR 15.5-21.8). Of the 14 assessable
patients who had successfully undergone ovarian cryopreservation, six had
developed premature ovarian insufficiency at a median age of 13.4 years (IQR 12.5
14.6), one of whom also had a natural pregnancy. Of the six assessable patients
who had declined the procedure, one had developed premature ovarian
insufficiency. Assessment of ovarian function was possible for 141 of the 376
patients who were not offered cryopreservation; one of these patients had
developed premature ovarian insufficiency. The cumulative probability of
developing premature ovarian insufficiency after treatment was completed was
significantly higher for patients who met the criteria for ovarian tissue
cryopreservation than for those who did not (15-year probability 35% [95% CI 10
53] vs 1% [0-2]; p<0.0001; hazard ratio 56.8 [95% CI 6.2-521.6] at 10 years).
INTERPRETATION: The results of this analysis show that the Edinburgh selection
criteria accurately identify the few girls and young women who will develop
premature ovarian insufficiency, and validate their use for selection of patients
for ovarian tissue cryopreservation. Further follow-up of this cohort of patients
is likely to allow refinement of the criteria for this experimental procedure in
girls and young women with cancer. FUNDING: UK Medical Research Council.
PMID- 25130996
TI - Ovarian tissue cryopreservation in children with cancer.
PMID- 25130995
TI - Short-term androgen suppression and radiotherapy versus intermediate-term
androgen suppression and radiotherapy, with or without zoledronic acid, in men
with locally advanced prostate cancer (TROG 03.04 RADAR): an open-label,
randomised, phase 3 factorial trial.
AB - BACKGROUND: We investigated whether 18 months of androgen suppression plus
radiotherapy, with or without 18 months of zoledronic acid, is more effective
than 6 months of neoadjuvant androgen suppression plus radiotherapy with or
without zoledronic acid. METHODS: We did an open-label, randomised, 2 * 2
factorial trial in men with locally advanced prostate cancer (either T2a N0 M0
prostatic adenocarcinomas with prostate-specific antigen [PSA] >=10 MUg/L and a
Gleason score of >=7, or T2b-4 N0 M0 tumours regardless of PSA and Gleason
score). We randomly allocated patients by computer-generated minimisation-
stratified by centre, baseline PSA, tumour stage, Gleason score, and use of a
brachytherapy boost--to one of four groups in a 1:1:1:1 ratio. Patients in the
control group were treated with neoadjuvant androgen suppression with leuprorelin
(22.5 mg every 3 months, intramuscularly) for 6 months (short-term) and
radiotherapy alone (designated STAS); this procedure was either followed by
another 12 months of androgen suppression with leuprorelin (intermediate-term;
ITAS) or accompanied by 18 months of zoledronic acid (4 mg every 3 months for 18
months, intravenously; STAS plus zoledronic acid) or by both (ITAS plus
zoledronic acid). The primary endpoint was prostate cancer-specific mortality.
This analysis represents the first, preplanned assessment of oncological
endpoints, 5 years after treatment. Analysis was by intention-to-treat. This
trial is registered with ClinicalTrials.gov, number NCT00193856. FINDINGS:
Between Oct 20, 2003, and Aug 15, 2007, 1071 men were randomly assigned to STAS
(n=268), STAS plus zoledronic acid (n=268), ITAS (n=268), and ITAS plus
zoledronic acid (n=267). Median follow-up was 7.4 years (IQR 6.5-8.4). Cumulative
incidences of prostate cancer-specific mortality were 4.1% (95% CI 2.2-7.0) in
the STAS group, 7.8% (4.9-11.5) in the STAS plus zoledronic acid group, 7.4% (4.6
11.0) in the ITAS group, and 4.3% (2.3-7.3) in the ITAS plus zoledronic acid
group. Cumulative incidence of all-cause mortality was 17.0% (13.0-22.1), 18.9%
(14.6-24.2), 19.4% (15.0-24.7), and 13.9% (10.3-18.8), respectively. Neither
prostate cancer-specific mortality nor all-cause mortality differed between
control and experimental groups. Cumulative incidence of PSA progression was
34.2% (28.6-39.9) in the STAS group, 39.6% (33.6-45.5) in the STAS plus
zoledronic acid group, 29.2% (23.8-34.8) in the ITAS group, and 26.0% (20.8-31.4)
in the ITAS plus zoledronic acid group. Compared with STAS, no difference was
noted in PSA progression with ITAS or STAS plus zoledronic acid; however, ITAS
plus zoledronic acid reduced PSA progression (sub-hazard ratio [SHR] 0.71, 95% CI
0.53-0.95; p=0.021). Cumulative incidence of local progression was 4.1% (2.2-7.0)
in the STAS group, 6.1% (3.7-9.5) in the STAS plus zoledronic acid group, 1.5%
(0.5-3.7) in the ITAS group, and 3.4% (1.7-6.1) in the ITAS plus zoledronic acid
group; no differences were noted between groups. Cumulative incidences of bone
progression were 7.5% (4.8-11.1), 14.6% (10.6-19.2), 8.4% (5.5-12.2), and 7.6%
(4.8-11.2), respectively. Compared with STAS, STAS plus zoledronic acid increased
the risk of bone progression (SHR 1.90, 95% CI 1.14-3.17; p=0.012), but no
differences were noted with the other two groups. Cumulative incidence of distant
progression was 14.7% (10.7-19.2) in the STAS group, 17.3% (13.0-22.1) in the
STAS plus zoledronic acid group, 14.2% (10.3-18.7) in the ITAS group, and 11.1%
(7.6-15.2) in the ITAS plus zoledronic acid group; no differences were recorded
between groups. Cumulative incidence of secondary therapeutic intervention was
25.6% (20.5-30.9), 28.9% (23.5-34.5), 20.7% (16.1-25.9), and 15.3% (11.3-20.0),
respectively. Compared with STAS, ITAS plus zoledronic acid reduced the need for
secondary therapeutic intervention (SHR 0.67, 95% CI 0.48-0.95; p=0.024); no
differences were noted with the other two groups. An interaction between trial
factors was recorded for Gleason score; therefore, we did pairwise comparisons
between all groups. Post-hoc analyses suggested that the reductions in PSA
progression and decreased need for secondary therapeutic intervention with ITAS
plus zoledronic acid were restricted to tumours with a Gleason score of 8-10, and
that ITAS was better than STAS in tumours with a Gleason score of 7 or lower.
Long-term morbidity and quality-of-life scores were not affected adversely by 18
months of androgen suppression or zoledronic acid. INTERPRETATION: Compared with
STAS, ITAS plus zoledronic acid was more effective for treatment of prostate
cancers with a Gleason score of 8-10, and ITAS alone was effective for tumours
with a Gleason score of 7 or lower. Nevertheless, these findings are based on
secondary endpoint data and post-hoc analyses and must be regarded cautiously.
Long- term follow-up is necessary, as is external validation of the interaction
between zoledronic acid and Gleason score. STAS plus zoledronic acid can be ruled
out as a potential therapeutic option. FUNDING: National Health and Medical
Research Council of Australia, Novartis Pharmaceuticals Australia, Abbott
Pharmaceuticals Australia, New Zealand Health Research Council, New Zealand
Cancer Society, University of Newcastle (Australia), Calvary Health Care (Calvary
Mater Newcastle Radiation Oncology Fund), Hunter Medical Research Institute,
Maitland Cancer Appeal, Cancer Standards Institute New Zealand.
PMID- 25130997
TI - Dual targeting of HER2 with lapatinib and trastuzumab.
PMID- 25130999
TI - Is elevated beta-hexosaminidase activity a potential biomarker for Parkinson's
disease?
PMID- 25130998
TI - Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO):
survival outcomes of a randomised, open-label, multicentre, phase 3 trial and
their association with pathological complete response.
AB - BACKGROUND: Findings from the randomised phase 3 NeoALTTO trial in women with
HER2-positive early breast cancer showed that the combination of lapatinib and
trastuzumab significantly improved rates of pathological complete response
compared with either drug alone. Here, we report data for the prespecified
secondary endpoints of event-free and overall survival, and assess the
association between these outcomes and pathological complete response. METHODS:
We enrolled women with HER2-positive early breast cancer and randomly assigned
them to receive oral lapatinib (1500 mg), intravenous trastuzumab (4 mg/kg
loading dose followed by 2 mg/kg), or lapatinib (1000 mg) plus trastuzumab (same
dose as for single agent) in combination for 6 weeks, followed by an additional
12 weeks of the assigned anti-HER2 therapy in combination with weekly paclitaxel
(80 mg/m(2)). Definitive surgery was done 4 weeks after the last dose of
paclitaxel. After surgery, women received three cycles of FEC (fluorouracil 500
mg/m(2) plus epirubicin 100 mg/m(2) plus cyclophosphamide 500 mg/m(2)) given
intravenously every 3 weeks, followed by 34 weeks of the same assigned
neoadjuvant anti-HER2 therapy. The primary endpoint was pathological complete
response. Secondary endpoints included event-free and overall survival (intention
to-treat analysis), and the association between pathological complete response
and event-free or overall survival (analysed by landmark analysis at 30 weeks
after randomisation). Follow-up is ongoing, and the trial is registered with
ClinicalTrials.gov, number NCT00553358. FINDINGS: 455 patients were enrolled: 154
(34%) were assigned to the lapatinib group, 149 (33%) to the trastuzumab group,
and 152 (33%) to the lapatinib plus trastuzumab group. At an event follow-up of
3.77 years (IQR 3.50-4.22), 3-year event-free survival was 78% (95% CI 70-84) in
the lapatinib group, 76% (68-82) in the trastuzumab group, and 84% (77-89) in the
combination group. Event-free survival did not differ between the lapatinib and
trastuzumab groups (HR 1.06, 95% CI 0.66-1.69, p=0.81), nor between the
combination and trastuzumab groups (0.78, 0.47-1.28, p=0.33). Median survival
follow-up was 3.84 years (IQR 3.60-4.24), and 3-year overall survival was 93%
(95% CI 87-96) for lapatinib, 90% (84-94) for trastuzumab, and 95% (90-98) for
combination therapy. Overall survival did not significantly differ between the
lapatinib and trastuzumab groups (HR 0.86, 95% CI 0.45-1.63, p=0.65), nor between
the combination and trastuzumab groups (0.62, 0.30-1.25, p=0.19). Landmark
analyses showed that 3-year event-free survival was significantly improved for
women who achieved pathological complete response compared with those who did not
(HR 0.38, 95% CI 0.22-0.63, p=0.0003), as was 3-year overall survival (0.35, 0.15
0.70, p=0.005). Adverse events occurred in 149 (99%) patients receiving
lapatinib, 142 (96%) patients receiving trastuzumab, and 147 (99%) patients
receiving combination therapy. The most common adverse events were diarrhoea,
rash or erythema, hepatic adverse events, and neutropenia (not related to FEC
administration), and were consistent with known safety profiles of lapatinib and
trastuzumab. Three primary and eight secondary cardiac events occurred, with no
significant difference in incidence between treatment groups for primary or any
cardiac events. INTERPRETATION: Although event-free survival or overall survival
did not differ between treatment groups, findings from our study confirm that
patients who achieve pathological complete response after neoadjuvant anti-HER2
therapy have longer event-free and overall survival than do patients without
pathological complete response. FUNDING: GlaxoSmithKline.
PMID- 25131000
TI - The efficacy of steroids for edema and ecchymosis after rhinoplasty: a meta
analysis.
AB - OBJECTIVES: Postoperative periorbital edema and ecchymosis following rhinoplasty
can result in dissatisfaction for both the surgeon and the patient. The goal of
this study was to perform a systematic review of the literature on the efficacy
of steroids on edema and ecchymosis during rhinoplasty. DATA SOURCES: MEDLINE,
SCOPUS, and Cochrane database. REVIEW METHODS: Two authors independently searched
the databases from their inception of article collection to February 2014.
Studies comparing perioperative steroid administration (steroid group) with no
treatment (control group) where the outcomes of interest were edema and
ecchymosis on postoperative days were included in the analysis. Overall, a total
of nine trials met the inclusion criteria of this study, with a total sample size
of 312 patients. RESULTS: The lower and upper eyelid edema during the 7 days
postoperatively was statistically decreased in the steroid group versus control
group. The lower and upper eyelid ecchymosis in the steroid group was
significantly decreased in comparison to the control group for the first 4 days
follow surgery. Regarding the outcome comparison between single-dose and multiple
dose administration of steroids, the multiple-dose administration decreased edema
and ecchymosis significantly compared to single-dose administration after the
fourth day. CONCLUSIONS: Perioperative administration of steroid during
rhinoplasty could reduce the level of edema and eyelid ecchymosis. Multiple-dose
administration of steroids has more advantages in terms of the outcomes of late
postoperative edema and ecchymosis compared to a single-dose regimen.
PMID- 25131001
TI - The antimicrobial activity of fruits from some cultivar varieties of Rubus idaeus
and Rubus occidentalis.
AB - Raspberries, derived from different cultivar varieties, are a popular ingredient
of everyday diet, and their biological activity is a point of interest for
researchers. The ethanol-water extracts from four varieties of red (Rubus
idaeus'Ljulin', 'Veten', 'Poranna Rosa') and black (Rubus occidentalis'Litacz')
raspberries were evaluated in the range of their antimicrobial properties as well
as phenolic content - sanguiin H-6, free ellagic acid and anthocyanins. The
antimicrobial assay was performed with the use of fifteen strains of bacteria,
both Gram-negative and Gram-positive. The antimicrobial activity of the extracts
varied and depended on the analysed strain of bacteria and cultivar variety, with
the exception of Helicobacter pylori, towards which the extracts displayed the
same growth inhibiting activity. Two human pathogens Corynebacterium diphtheriae
and Moraxella catarrhalis proved to be the most sensitive to raspberry extracts.
Contrary to the extracts, sanguiin H-6 and ellagic acid were only active against
eight and nine bacterial strains, respectively. The determined MIC and MBC values
of both compounds were several times lower than the tested extracts. The highest
sensitivity of Corynebacterium diphtheriae to extracts from both black and red
raspberries may be due to its sensitivity to sanguiin H-6 and ellagic acid.
PMID- 25131003
TI - Failure of replicating the association between hippocampal volume and 3 single
nucleotide polymorphisms identified from the European genome-wide association
study in Asian populations.
AB - Hippocampal volume is a key brain structure for learning ability and memory
process, and hippocampal atrophy is a recognized biological marker of Alzheimer's
disease. However, the genetic bases of hippocampal volume are still unclear
although it is a heritable trait. Genome-wide association studies (GWASs) on
hippocampal volume have implicated several significantly associated genetic
variants in Europeans. Here, to test the contributions of these GWASs identified
genetic variants to hippocampal volume in different ethnic populations, we
screened the GWAS-identified candidate single-nucleotide polymorphisms in 3
independent healthy Asian brain imaging samples (a total of 990 subjects). The
results showed that none of these single-nucleotide polymorphisms were associated
with hippocampal volume in either individual or combined Asian samples. The
replication results suggested a complexity of genetic architecture for
hippocampal volume and potential genetic heterogeneity between different ethnic
populations.
PMID- 25131002
TI - Age-associated evolution of plasmatic amyloid in mouse lemur primates:
relationship with intracellular amyloid deposition.
AB - Alzheimer's disease (AD) is the most common age-related neurodegenerative
disorder. Amyloid-beta peptide (Abeta) deposition in the brain is one of its
hallmarks, and the measure of plasma Abeta is considered to be a biomarker for
anti-amyloid drug efficacy in animal models of AD. However, age-associated
plasmatic Abeta modulation in animal models is practically never addressed in the
literature. Mouse lemur primates are used as a model of normal and AD-like
cerebral aging. Here, we studied the effect of age on plasmatic Abeta in 58 mouse
lemurs aged from 1 to 10 years. A subset of animals presented high plasmatic
Abeta, and the proportion of animals with high plasmatic Abeta was higher in aged
animals as compared with young ones. Histologic evaluation of the brain of some
of these animals was carried out to assess extracellular and intracellular
amyloid load. In aged lemurs, plasmatic Abeta was negatively correlated with the
density of neurons accumulating deposits of Abeta.
PMID- 25131005
TI - Response to Dr. Sertoglu and colleagues.
PMID- 25131004
TI - Single neuropsychological test scores associated with rate of cognitive decline
in early Alzheimer disease.
AB - Alzheimer disease (AD) characteristically begins with episodic memory impairment
followed by other cognitive deficits; however, the course of illness varies, with
substantial differences in the rate of cognitive decline. For research and
clinical purposes it would be useful to distinguish between persons who will
progress slowly from persons who will progress at an average or faster rate. Our
objective was to use neurocognitive performance features and disease-specific and
health information to determine a predictive model for the rate of cognitive
decline in participants with mild AD. We reviewed the records of a series of 96
consecutive participants with mild AD from 1995 to 2011 who had been administered
selected neurocognitive tests and clinical measures. Based on Clinical Dementia
Rating (CDR) of functional and cognitive decline over 2 years, participants were
classified as Faster (n = 45) or Slower (n = 51) Progressors. Stepwise logistic
regression analyses using neurocognitive performance features, disease-specific,
health, and demographic variables were performed. Neuropsychological scores that
distinguished Faster from Slower Progressors included Trail Making Test - A,
Digit Symbol, and California Verbal Learning Test (CVLT) Total Learned and
Primacy Recall. No disease-specific, health, or demographic variable predicted
rate of progression; however, history of heart disease showed a trend. Among the
neuropsychological variables, Trail Making Test - A best distinguished Faster
from Slower Progressors, with an overall accuracy of 68%. In an omnibus model
including neuropsychological, disease-specific, health, and demographic
variables, only Trail Making Test - A distinguished between groups. Several
neuropsychological performance features were associated with the rate of
cognitive decline in mild AD, with baseline Trail Making Test - A performance
best separating those who declined at an average or faster rate from those who
showed slower progression.
PMID- 25131007
TI - Organ transplants and education: experience of the Universidade Federal de
Ciencias da Saude de Porto Alegre with subjects.
AB - INTRODUCTION: Today there is an insufficient number of donated organs in Brazil.
This is particularly due to the general population's and health care
professionals' lack of information. Therefore, with this project we intend to
consolidate knowledge on organ donation to teach health care students of
different areas so they are able to propagate such knowledge. MATERIALS AND
METHODS: In 2006, at Universidade Federal de Ciencias da Saude de Porto Alegre,
an "Organ donation and transplants" subject was created, with the aim to educate
health care students. In the next years, it was split in two subjects, named
"Introduction to transplants" and "Donation and transplants." By enrolling,
students get theoretical classes and practical experience in out- and inpatient
facilities and in surgical environments at the Santa Casa Hospital Complex.
Furthermore, they can participate in campaigns at parks, stadiums, and health
care fairs that take place at several schools in Porto Alegre. To finish the
subjects, students present a conclusion report. RESULTS: Seven years after
implementation of the subject, and with more than 400 students enrolled, several
accomplishments can be highlighted. For example, the creation of the Organ
Transplantation League, the implementation of a day to spread conception of the
donation-transplant process (with the elaboration of a Web page on the subject),
and the release of a book on the subject written by students and professors.
DISCUSSION AND CONCLUSION: Health care professionals' education is a central
point in donation and transplant process. This is because they become,
inevitably, educators, and this brings a long-term consequence, consisting of
enhanced logistics skills on brain-death diagnosis and further transfer of
information to the population (hopefully reducing denial by families at the time
of the donation). We conclude that this is a project to be followed by other
medical schools so that, effectively, the number of donors increases and,
consequently, the transplantation of organs and tissues as well.
PMID- 25131008
TI - Reasons for family refusal of ocular tissue donation.
AB - INTRODUCTION: Corneal donations do not fill the transplant demand. The waiting
list had 5512 individuals in Brazil and 143 in Rio Grande do Sul in December
2012. The aim of this study was to identify the reasons for family refusal of
ocular tissues donation. METHODS: This retrospective study analyzed interview
records for ocular tissue procurement performed in a general, public university
hospital located in Southern Brazil between January 2008 and December 2012. It
identified the reasons of family refusal for ocular tissue donation. RESULTS: A
total of 1010 interviews for ocular tissues procurement were performed. From
these, 513 (50.79%) refused donation with the following reasons: 60 (11.69%)
family members were unaware of the desire of the potential donor, 153 (29.82%) of
potential donors spoke against donation in life, 113 (22.02%) family members were
undecided about the donation, 156 (30.40%) family members were against donation,
3 (0.58%) family members were unhappy with the service, 11 (2.14%) family members
were afraid of body release delay, 6 (1.16%) families expressed religious
convictions against donation, and 11 (2.14%) family members wanted to keep the
body intact. CONCLUSION: There are many reasons for ocular tissues donation
refusal, and the knowledge provides better strategies for family interviews. In
this study, most of the reasons, around 90%, can be related to lack of
information or communication about the subject. Greater awareness of the
population about the subject can be a good way to increase ocular tissue
procurement indexes.
PMID- 25131009
TI - Family informed consent to organ donation--who performs better: organ procurement
organizations, in-hospital coordinators, or intensive care unit professionals?
AB - Successful organ donation in countries adopting informed consent legislation
depends on adequate interviewing of potential donors' families. As the number of
both referral and effective donors in Brazil increases, health care managers
argue whether educational efforts should be directed toward training in-hospital
coordinators (IHC)--based on the "Spanish model"--or on the creation of extra
hospital-based professionals (Organ Procurement Organizations [OPOs], the
"American model"). Meanwhile, many potential donor families are still approached
by intensive care unit (ICU) professionals not trained in donation interviews.
The aim of our study was to compare performances in obtaining informed consent
from potential donors' families, according to the type of health care
professional conducting the interviews: OPO, IHC, or ICU staff. In this
retrospective 2-year study performed in Rio de Janeiro, Brazil, we observed an
increase in referrals (285 to 411) and consent rates (48.1% to 55.7%). Each year,
OPO professionals conducted most family interviews (58.6% and 60.4%,
respectively) and obtained better consent rates (63.5% and 64.5%, respectively),
when compared to IHC (41.8% and 53.7%, respectively) or untrained ICU
professionals (22.1% and 13.4%, respectively). Our results show that adequate
professional training is necessary for obtaining family consent for organ
donation. Both established international policies for organ procurement and
donation, namely the "Spanish model" with its IHCs or the "American model" of
extra-hospital OPOs, may equally achieve this task. However, family interviews
performed by untrained ICU professionals result in low donation rates and should
be discouraged.
PMID- 25131010
TI - The family interview in the process of donating organs and tissues for
transplantation: perceptions of potential donors' relatives.
AB - BACKGROUND: The family interview is a complex phase of the organ donation process
because it involves aspects of the interviewer, the interviewee, the interview
location, and ethical and legal issues. However, there are few publications on
this phase of the donation process. This study aimed to reveal the meaning
assigned to the interview phase, in the process of donating organs and tissues
for transplantation, by the families of potential donors. METHODS: We performed a
qualitative study of the phenomenologic aspect, within the modality "structure
situated phenomena." The study included the participation of 10 families.
RESULTS: After analyzing the interviews, the meaning of the interview was
unveiled by the family members. CONCLUSIONS: The statements revealed that the
family interview is considered to be an important step for warnings,
clarifications, and encouraging families to think about the possibility of
donating to save and/or improve the quality of life of people in need for a
transplant, and that studies contribute to the technical and scientific
qualification of the interviewer as well as stimulate discussion among health
professionals to improve the interviewing process.
PMID- 25131011
TI - Genetic expression profile of human liver grafts in ischemia-reperfusion injury:
comparison of familial amyloidotic polyneuropathy and deceased-donor liver
grafts.
AB - This study aimed to compare the histologic and molecular gene expression at
several surgical times (beginning of harvesting, T0; end of cold ischemia period,
T1; and after reperfusion, T2) to characterize the ischemia-reperfusion injury
(IRI) in deceased-donor liver grafts harvested from patients with familial
amyloidotic polyneuropathy (FAP). For this purpose, 54 patients undergoing liver
transplantation were studied and divided into 3 groups: deceased donor to
cirrhotic recipient (group 1; n = 27), deceased donor to FAP recipient (group 2;
n = 15), and FAP donor to cirrhotic recipient (group 3; n = 12). The main
comparison was performed between a histologic score (Suzuki score, adding
steatosis and neutrophil infiltration), and molecular gene expression of the
following genes: interleukin (IL) 1beta, IL-6, E-selectin, Fas-ligand, granzyme
B, heme oxygenase 1 (HO1), and nitric oxide synthetase (iNOS2A). We observed less
neutrophil infiltration levels in group 3 in sample T0 (P = .0082), which was
associated with gene expression of HO1 in the biopsies at T2 (P = .022). In group
3, the molecular expression of genes related to attenuated proinflammatory
reaction during IRI, iNOS2A at T0 and HO1 at T2, was detected. We conclude that
FAP liver grafts express differently the genes associated with an attenuated
proinflammatory reaction, presenting less neutrophil infiltration at harvesting.
These findings add more knowledge about the better short-term outcomes in
patients receiving this type of liver graft.
PMID- 25131012
TI - Evaluation of the reasons for nonacceptance of kidneys retrieved or offered in
Rio Grande do Sul and Pais Vasco.
AB - In Rio Grande do Sul (RS), as in Pais Vasco (PV), some kidneys are retrieved or
offered and not accepted for transplantation. This study aimed to evaluate the
profile of the available kidneys and the reasons for them not being accepted in
the 2 regions, and to compare the characteristics of the organs and reasons for
refusal. All of the kidneys retrieved or offered in RS in December 2012 and in PV
from September to December 2012 were evaluated. Data were collected from each
local donation registry. There were 61 kidneys available in RS and 61 in PV in
the study period. Of these, 16 kidneys (26%) in RS and 27 (44%) in PV were not
implanted. The age of the donors was higher in PV (59 years) than in RS (45
years; P = .000), as was the age of the donors of accepted kidneys (62 and 41
years old, respectively; P = .000). The proportion of donors considered to be
"extended criteria" was higher in PV (78%) than in RS (47%; P = .001), and the
refusal rate of the kidneys from these donors was the same in the 2 regions. The
reasons for not using the kidneys in RS and in PV were similar and absolute. It
is concluded that there is no organ waste in the 2 regions, but that the offer of
kidneys can be expanded in RS by considering elderly donors for evaluation, even
if this means a higher number of refused organs.
PMID- 25130992
TI - Linking temporal changes in bacterial community structures with the detection and
phylogenetic analysis of neutral metalloprotease genes in the sediments of a
hypereutrophic lake.
AB - We investigated spatial and temporal variations in bacterial community structures
as well as the presence of three functional proteolytic enzyme genes in the
sediments of a hypereutrophic freshwater lake in order to acquire an insight into
dynamic links between bacterial community structures and proteolytic functions.
Bacterial communities determined from 16S rRNA gene clone libraries markedly
changed bimonthly, rather than vertically in the sediment cores. The phylum
Firmicutes dominated in the 4-6 cm deep sediment layer sample after August in
2007, and this correlated with increases in interstitial ammonium concentrations
(p < 0.01). The Firmicutes clones were mostly composed of the genus Bacillus. npr
genes encoding neutral metalloprotease, an extracellular protease gene, were
detected after the phylum Firmicutes became dominant. The deduced Npr protein
sequences from the retrieved npr genes also showed that most of the Npr sequences
used in this study were closely related to those of the genus Bacillus, with
similarities ranging from 61% to 100%. Synchronous temporal occurrences of the
16S rRNA gene and Npr sequences, both from the genus Bacillus, were positively
associated with increases in interstitial ammonium concentrations, which may
imply that proteolysis by Npr from the genus Bacillus may contribute to the
marked increases observed in ammonium concentrations in the sediments. Our
results suggest that sedimentary bacteria may play an important role in the
biogeochemical nitrogen cycle of freshwater lakes.
PMID- 25131013
TI - Ten years' evaluation of potential pancreas donors in Sao Paulo, Brazil.
AB - BACKGROUND: Pancreas transplantation is a treatment for advanced type 1 diabetes
and offers significant improvement in quality of life. Recent advances in
surgical techniques and immunosuppression regimes lead to good outcomes. However,
despite significant higher rates of multiorgan donors in Brazil, pancreas
transplantation seems to have remained stable. This study aimed to investigate
the acceptance rate of potential pancreas donors in the past 10 years in Sao
Paulo State. METHODS: We retrospectively evaluated potential pancreas donors
characteristics and its acceptance rate in Sao Paulo State in the past 10 years.
We divided this period into 2 eras: 1st era from January 2003 to January 2008;
and 2nd era from January 2008 to January 2013. Data were obtained from Sao
Paulo's government official website. RESULTS: During the whole period, 5,005
deceased donors of all ages were available for pancreas transplantation.
According to eras, we had 1,588 donors in the 1st and 3,417 in the 2nd era. In
the 2nd era, donors >49 years old were significantly more common (P < .001).
Blood test abnormalities, donor comorbidities, and high dosage of vasopressors
also were significantly higher in the 2nd era. Rate of graft acceptance had a
significant decrease in the 2nd era, from 46.4% to 25% (P < .05). CONCLUSIONS:
Despite greater organ availability, pancreas transplantations performed in Sao
Paulo State remained stable. Rate of graft acceptance is dramatically lower in
more recent years.
PMID- 25131014
TI - Profile of organ donors in Ceara, northeastern Brazil, from 1998 to 2012.
AB - The use of cadaver donors for transplantation is often the only alternative in
the treatment of patients with organ failure. The purpose of this study was to
draw a comprehensive profile of solid organ donors in Ceara, northeastern Brazil,
from 1998 to 2012. The study was retrospective and based on secondary data
regarding sex, age, blood typing, and cause of brain death obtained from the
solid organ donor database of the Ceara Transplantation Center covering the
period November 1998 to December 2012. During the study period, 976 donors (69%
male) were used. Donors were distributed in 4 age groups as follows: 12.9% <18
years, 50.9% 18-40 years, 28.5% 41-60 years, and 7.7% >60 years. The average age
was 35 +/- 16 years. On the average, female donors were older than male donors
(38.4 +/- 17 y vs 33.5 +/- 16 y; P < .0001). Men were predominant in the age
groups 18-40 y (75.3%; P < .0001) and 41-60 y (59.4%; P < .0001). The main causes
of brain death were traumatic brain injury (TBI) (56.7%) and stroke (33.1%). The
former was more common in men (P < .0001), the latter in women (P < .0001). TBI
was caused by traffic accidents (51.4%), of which 50.7% were motorcycle
accidents, and urban violence (22.6%), of which 71.2% were associated with
firearms. The number of donations increased in the study period (11.2 donors per
million population in 1998-2002 to 68.1 in 2008-2012). In Ceara, solid organ
donation is on the rise. The predominant donor profile was young men aged 18-40
years with brain death due to TBI caused by traffic accidents and urban violence.
PMID- 25131015
TI - Waiting for a kidney transplant: association with anxiety and stress.
AB - BACKGROUND: The pretransplantation period is characterized by many stressful
events that can result in symptoms of anxiety and stress and ultimately can have
a negative impact on graft outcome. Our objective was to evaluate the association
between symptoms of anxiety and stress in patients awaiting kidney
transplantation. METHODS: This was a transversal study describing 50 randomly
selected patients undergoing hemodialysis and waitlisted for kidney
transplantation. We collected social and demographic data, and adopted the Beck
Anxiety Inventory and the Lipp Stress Symptoms for Adults Inventory to
respectively evaluate anxiety and stress. RESULTS: The mean age was 50.2 +/- 11.7
years, 54% of patients were female, time on dialysis was 6.5 +/- 4.5 years, and
transplant waitlist time was 5.9 +/- 4.4 years. Forty-six percent of patients
were married or had a stable relationship, 50% were illiterate or had only
finished primary school, and 64% were pensioners. Stress was documented in 60% of
patients, of which 30% had severe stress, whereas 56% of patients showed symptoms
of anxiety. The presence of stress was associated with longer waitlist time (P =
.006) and longer time on dialysis (P = .052). Less severe stress was associated
with higher education level (P = .031), whereas patients in more advanced phases
of stress showed higher levels of anxiety. After a multivariate analysis, stress
was 3.6 times (CI 1.34 to 9.89) more frequent among individuals with anxiety.
CONCLUSIONS: Stress and anxiety were prevalent in patients on a waitlist and were
associated with social and chronic kidney disease-related patterns. This
observation can stimulate the adoption of strategies for the prevention of stress
and anxiety, avoiding posttransplantation complications, such as nonadherence to
treatment.
PMID- 25131016
TI - Historical cohort with diabetes mellitus after kidney transplantation and
associated factors of its development in adult patients of a transplantation
reference center in the State of Ceara, Brazil.
AB - Post-transplantation diabetes mellitus (PTDM) is an important complication
related to kidney transplantation (KT), and its occurrence is associated with
increased morbidity and mortality. Nevertheless, KT is considered to be the most
effective treatment option that offers better quality of life for patients with
end-stage kidney disease. This study aimed to describe the occurrence of PTDM and
the risk factors associated with its development in kidney transplant patients of
a transplantation reference center in the State of Ceara (Brazil). This
historical cohort study, based on medical records data, included adult patients
undergoing KT from January 2006 to December 2010 in a public tertiary hospital.
Multivariate analysis was performed with the use of a logistic regression model,
with PTDM presence as dependent variable and the possible risk factors under
study as independent variables. Throughout the evaluated period, 430 KTs were
performed; 92 patients were excluded. Diabetes mellitus was already present in
9.2% of patients before KT. Hyperglycemia during the 1st month after
transplantation occurred in 34.5% of recipients, and the occurrence of PTDM to
the end of study was 19.9%. Factors associated with PTDM development were:
fasting plasma glucose 1 month after KT (P < .001; odds ratio [OR] 1.05),
deceased-donor KT (P = .015; OR 3.53), impaired fasting glucose before
transplantation (P = .014; OR 4.10), and acute rejection occurrence (P = .003; OR
6.43). High PTDM occurrence was found, in accordance with the literature.
Identification of factors associated with PTDM development, as well as its early
diagnosis, could result in long-term improvement in patient and graft survivals.
PMID- 25131017
TI - Kidney transplantation across a positive crossmatch: a single-center experience.
AB - BACKGROUND: Kidney transplantation is the treatment of choice for end-stage renal
disease, with improved mortality and quality of life compared with dialysis.
Desensitization protocols have allowed kidney transplantation of highly
sensitized patients, who have a lower probability to receive a matching kidney
from a deceased or living donor. The aim of this work was to analyze the post
transplantation period of highly HLA-sensitized patients with positive flow
cytometry crossmatch against donor cells. METHODS: Following an observational,
retrospective design, we investigated 16 highly sensitized patients who underwent
kidney or kidney-pancreas transplantation, assessing the impact of
desensitization protocols and investigating treatment-related complications,
graft function, antibody-mediated rejection (AMR) rate, and graft and patient
survivals. RESULTS: We studied 16 patients with positive flow cytometry
crossmatch, who were divided into 2 groups based on whether they were submitted
to a desensitization protocol or not. Patients who were desensitized underwent
transplantation in later years, had higher immunologic risk (panel reactive
antibody peak 62% vs 33%; P = .038), higher percentage of 2nd kidney transplant
(75% vs 25%; P = .066), and higher percentage of donor-specific anti-HLA
antibodies identified (P = .028). A majority of patients were desensitized with
high-dose intravenous immunoglobulin and plasmapheresis, and 5 patients received
rituximab. Acute AMR rate was of 38%, and rituximab was associated with fewer
episodes of AMR. Only 1 patient had graft failure, due to chronic humoral
rejection, and the remaining maintained good graft function (mean serum
creatinine value of 1.33 mg/dL). No patient died and few complications related to
immunossupression were observed. CONCLUSIONS: Desensitization protocols were safe
and allowed kidney transplantation in highly sensitized patients that probably
would never undergo transplantation and gave the opportunity of living-donor
transplant to patients with anti-HLA antibodies against the donor.
PMID- 25131018
TI - C4d deposits in borderline rejection: an early marker for chronic renal
dysfunction?
AB - The impact of borderline rejection in renal graft remains controversial. The aim
of this study was to analyze the presence of C4d deposits in peritubular
capillaries and macrophage infiltration in renal biopsies with diagnosis of
borderline rejection ant its effect on graft function. Thirty-one renal
transplant recipients with a diagnosis of borderline rejection were included.
Initial and sequential biopsies were analyzed for morphology, C4d, and macrophage
staining and compared with clinical data. Initial biopsies showed 12 samples to
be C4d positive, associated with a higher incidence of delayed graft function,
earlier post-transplantation time, higher acute tubular necrosis score,
capillaritis, and glomerular macrophage infiltration, and a lower level of
tubulitis, interstitial fibrosis, and tubular atrophy compared with the C4d
negative samples. In sequential biopsies, 5 patients from the negative group
turned C4d positive. Patients with >=1 positive C4d biopsy (n = 17) showed lower
renal graft function at 6 months (1.8 +/- 0.8 vs 1.4 +/- 0.5 mg/dL; P < .01), 1
year (2.1 +/- 1 vs 1.5 +/- 0.5 mg/dL; P < .01), and 2 years (2.3 +/- 1.3 vs 1.5
+/- 0.7 mg/dL; P < .05) of follow-up. The expression of C4d in peritubular
capillaries of renal biopsies classified as borderline rejection was associated
with a worse prognosis for the renal allograft.
PMID- 25131020
TI - Renal transplantation in human immunodeficiency virus-positive patients: a report
of four cases.
AB - INTRODUCTION: Renal transplantation (RT) in patients infected with human
immunodeficiency virus (HIV) has significantly improved under the advent of
combined antiretroviral therapy (cART). The authors describe their experience in
RT in patients with HIV from September 2010 to June 2013. CASES REPORT: Four
patients underwent transplantation (3 with HIV-1 and 1 with HIV-2), three
patients were male, and one was black. None were coinfected with hepatitis B
virus (HBV) or hepatitis C virus (HCV). Etiology of kidney disease was HIV
associated nephropathy (2 patients), immunoglobulin (Ig)A nephropathy, and
unknown. Average age at RT was 51 (range, 41-63) years. No patient was of high
immunologic risk. Immunosuppression consisted of basiliximab for induction and
prednisolone, tacrolimus (TAC), and mycophenolate mofetil for maintenance. TAC
levels varied considerably in the early days (8.5-46 ng/mL), requiring major
adjustments in TAC dose. Only the HIV-2 patient had delayed graft function. The
follow-up of patients with HIV-1 was 37, 19, and 16 months, and 3 months for the
HIV-2 patient. CD4+ T cells decreased in the early days after transplantation
with subsequent improvement, along with persistent virological suppression. In
the HIV-1 group there were no major infectious, cardiovascular, or neoplastic
complications. Nevertheless, the HIV-2 patient died 3 months after RT due to H1N1
pneumonia complicated by pulmonary aspergillosis. Average estimated (CKD- EPI)
glomerular filtration rate (eGFR) at 6 months was 85.6 mL/min/1.73 m(2).
CONCLUSION: Besides the difficulty in adjusting calcineurin inhibitors levels due
to its interaction with antiretroviral therapy, namely with protease inhibitors,
no patient had acute rejection. Furthermore, all patients presented an excellent
control of viro-immunologic parameters. At the last follow-up neither
cardiovascular events nor neoplastic complications were observed. Our results
highlight the favorable outcome of RT in HIV-1-infected patients. The HIV-2
patient died due to severe infection, and the clinical management and potential
benefit of RT in HIV-2-infected patients needs further study.
PMID- 25131021
TI - Predictive factors of graft-censored failure in pediatric kidney transplantation.
AB - Kidney transplantation in children has shown steady improvement in graft survival
outcome over the last decades. Using data obtained from the transplantation
registry of our center between 1984 and 2012, we assessed the independent
determinants of graft failure using the Cox proportional hazards regression.
Altogether, 128 recipients younger than 18 years of age at the time of kidney
transplantation and who had >3 months graft survival were studied. During 9.95
years of medium follow-up, 27 censored graft failures occurred. Censored graft
survival rates at 5, 10, 15, and 20 years post-transplantation were 93%, 82%,
70%, and 63%, respectively. Studied factors included recipient and donor age,
recipient gender, dialysis vintage, donor/recipient cytomegalovirus (CMV)
serology, panel-reactive antibody percentage, human leukocyte antigen
mismatching, previous transplantation number, donor type (deceased vs living
donation), cold ischemia time, induction therapy with antithymocyte globulin,
occurrence of acute tubular necrosis, and development of acute rejection. Using
univariate analysis, the significant predictors for graft-censored failure were
adult donor (P < .001), recipient age (P = .035), human leukocyte antigen
mismatching (P = .025), antithymocyte globulin induction (P = .03), and
development of acute rejection (P < .001). Two factors independently predicted
graft-censored failure in multivariate analysis. The odds ratios for graft
failure in patients with acute rejection and in children who received an organ of
an adult were 3.744 and 4.962, respectively. Pediatric recipients should receive
the first priority for allografts from pediatric donors and acute rejection
should be meticulously prevented.
PMID- 25131019
TI - Physical activity in daily life assessed by an accelerometer in kidney transplant
recipients and hemodialysis patients.
AB - BACKGROUND: Sedentary lifestyle is a problem among hemodialysis (HD) patients,
potentially attenuated after kidney transplantation. However, the effect of
kidney transplantation on physical activity has not been thoroughly investigated.
OBJECTIVE: This study sought to evaluate the physical activity in daily life in
kidney transplant recipients (KTRs) compared with HD patients and to explore its
relationship with clinical variables. METHODS: A cross-sectional study enrolled
KTRs who received transplants at least 6 months before the study (N = 23; 48.3 +/
10.3 years) and patients undergoing HD for at least 6 months (N = 20; 47.3 +/-
12.6 years). Time spent in different activities (walking, standing, sitting, and
lying down) and number of steps taken, measured by a multiaxial accelerometer
used for 12 h/d on 2 consecutive days for KTRs and on 4 consecutive days for HD
patients, were evaluated. RESULTS: KTRs engaged in more active time per day (sum
of walking and standing time) than HD patients (311 +/- 87 vs 196 +/- 54 min/d; P
= .001), with longer walking (106 +/- 53 vs 70 +/- 27 min/d; P = .008) and
standing time (205 +/- 55 vs 126 +/- 42 min/d; P < .001). Sixty-five percent of
KTRs were classified as active (>7500 steps/d) compared with only 20% of the HD
group (P < .05). The multivariate analysis showed that time posttransplantation
was significantly associated with walking time and active time. CONCLUSIONS: By
using an accelerometer, a precise method, this study showed that KTRs are
significantly more active in daily life than HD patients, and that daily physical
activity increases with time since transplantation.
PMID- 25131022
TI - Incidence, risk factors, and outcomes of delayed graft function in deceased donor
kidney transplantation in a Brazilian center.
AB - BACKGROUND: A high incidence of delayed graft function (DGF) after deceased donor
kidney transplantation occurs in Brazil. The reasons for such have not been
adequately studied. METHODS: We performed a retrospective cohort study of 346
kidney transplant recipients from deceased donors. DGF risk factors related to
the recipient, donor, and transplantation surgery were analyzed and correlated
with graft outcomes. A logistic regression analysis was used to identify
independent risk factors and patient and graft survival were assessed using
Kaplan-Meier curves. RESULTS: The incidence of DGF was 70.8% (245 cases). Our
final model of multivariate analysis showed that DGF is associated (P < .05) with
donor final serum creatinine (relative risk [RR], 1.84; 95% confidence interval
[CI], 1.26-2.70), donor age (RR, 1.02 [1.0-1.033]), receiving a kidney from
national offer (RR, 2.44 [1.06-5.59]), and need for antibody induction (RR, 2.87
[1.33-6.18]). Outcomes that were associated with DGF were longer length of
hospital stay (32.5 +/- 20.5 vs 18.8 +/- 16.3 days; P = .01), higher incidence of
acute rejection (37.8 vs 12.9%; P < .01), worse graft survival at 1 year (83.5%
vs 93.9%; P < .01), and higher levels of serum creatinine at 3, 6, and 12 months
(P < .05). There was no difference in patient survival and the occurrence of
acute rejection did not influence the survival of patients or grafts. CONCLUSION:
DGF was associated with higher donor final serum creatinine, donor age, receiving
a kidney from the national supply, and need for antibody induction. Most
importantly, DGF was associated with worse outcomes.
PMID- 25131023
TI - Kidney retransplantation: removal or persistence of the previous failed
allograft?
AB - A significant percentage of patients with failed renal graft are candidates for
retransplantation. The outcomes of retransplantation are poorer than those of
primary transplantation and sensitization is documented to be a major reason. The
management of a failed allograft that is not immediately symptomatic is still
very controversial. The aim of this study was to determine the impact of the
failed allograft nephrectomy on a subsequent transplantation and its importance
in the sensitization. We performed a retrospective analysis of the local
prospective transplantation registry of the outcome of 126 second kidney
transplantations among 2438 transplantations performed in our unit between June
1980 and March 2013, comparing those who underwent allograft nephrectomy prior to
retransplantation with those who retained the failed graft. Primary endpoints
were graft and patient survival. The levels of panel-reactive antibodies (PRA)
and rate of acute rejections on retransplantation outcomes were also studied.
Among the 126 patients who underwent a second renal transplantation, 76 (60.3%)
had a prior graft nephrectomy (Group A), whereas 50 (39.7%) kept their failed
graft (Group B). Group A showed significantly more positive PRA levels when
compared with the other group (38% vs 10%; P < .001), as measured before the most
recent transplantation, and a higher rate of acute rejection (19% vs 5.6%; P =
.016). There were 28 (36%) renal allograft losses for Group A and 18 (36%) for
those who had not had transplantectomy (P = not significant [NS]). One-, 3-, and
5-year graft survival rates were 96.6%, 90.7%, and 83.4%, respectively, in Group
A and 95%, 82%, and 68.4%, respectively, in Group B, with no statistical
differences (P = .19). Five-year actuarial patient survival rates in the 2 groups
was 89.3% and 82.8%, respectively (P = .55). Multivariate analysis showed that
PRA level and delayed graft function (DGF) had a statistically significant
influence on graft survival (P = .028; odds ratio [OR] = 1.029; and P = .024; OR
= 8.6), irrespective of whether the patient had graft nephrectomy or not. The
allosensitization indicated by PRA increases after transplantectomy and leads to
a higher incidence of acute rejection after retransplantation. Nephrectomy of
failed allograft does not seem to significantly influence the survival of a
subsequent graft. The decision to remove or retain a failed graft in the context
of retransplantation should thus be based on known clinical indications for the
procedure.
PMID- 25131024
TI - Post-transplantation weight gain: prevalence and the impact of steroid-free
therapy.
AB - INTRODUCTION: Weight gain after renal transplantation has a multifactorial
etiology, which can be associated with complications such as hypertension,
dyslipidemia and diabetes, with a probable impact on cardiovascular morbidity and
mortality post-transplantation. OBJECTIVE: The objectives of this study were to
investigate the prevalence of weight gain and obesity post-transplantation among
renal recipients of a hospital and to evaluate the impact of immunosuppressive
therapy without steroids. MATERIALS AND METHODS: We have evaluated all patients
who had kidney transplantations performed between January 2005 and December 2009
at General Hospital of Fortaleza, who were older than 18 years of age and had at
least 12 months of follow-up post-transplantation. Overweight was defined as body
mass index (BMI) between 25 and 30 kg/m(2) and obesity >30 kg/m(2). The
association between weight gain and the following variables was investigated: age
and gender of the recipient and the donor, donor type, steroid use, presence of
systemic arterial hypertension (SAH) and diabetes mellitus, creatinine, glucose,
cholesterol, and triglycerides. RESULTS: The study population included 203
recipients; 59.5% were males, their mean age systemic arterial hypertension (SAH)
was 37 years, and 64.2% had deceased donors. In regard to immunosuppression,
41.3% made use of steroids. After 36 months of follow-up, the average weight gain
was 6.6 kg in relation to the first month post-transplantation. Among the
variables studied, the recipient's younger age and female gender, the younger
donor, and the creatinine level were associated with greater weight gain after 36
months of transplantation. CONCLUSION: The percentage of weight gain was on
average 9% after 36 months post-transplantation, although the prevalence of
overweight and obesity increased significantly in the same period. The use of
steroid therapy had no impact on the percentage of weight gain post
transplantation, and association was observed only between the younger age and
the female gender of the recipient, the younger donor age, and the creatinine
level with the highest weight gain post-transplantation.
PMID- 25131025
TI - Metabolic surgery for the treatment of type 2 diabetes in pancreas after kidney
transplant candidates.
AB - Metabolic surgery for the treatment of type 2 diabetes mellitus (T2DM) in
patients not morbidly obese (BMI <35) has been widely studied. Taking into
account that ~12% of pancreas transplants are performed in patients with T2DM,
our goal was to evaluate the impact of metabolic surgery on the management of
obese patients with T2DM on waiting lists for a pancreas transplant. We performed
a Roux-en-Y gastrointestinal bypass in 5 patients with insulin-dependent T2DM who
were candidates for pancreas after kidney transplant and with a BMI <35. Three
patients became insulin independent by the end of the first year while the other
2 reduced their insulin requirements by 70%. Furthermore, all patients achieved
improved control of lipid levels. We concluded that the surgery was effective in
controlling blood glucose and lipid metabolism in these obese T2DM kidney
transplant recipients. In this population, a pancreas transplant, along with its
associated morbidity, may be avoided.
PMID- 25131026
TI - Fatigue effects in daily life activities of kidney transplant recipients.
AB - After undergoing kidney transplantation, some patients still face one symptom
that continues after the dialysis sessions: fatigue (physical and mental
tiredness that does not get better after resting). Fatigue effects in the
everyday lives of kidney transplant patients can be beneficially modified early
by changing this scenario. This is a quantitative study about the intensity and
impacts of fatigue in kidney transplant patients admitted to the Hypertension and
Kidney Hospital from October 2011 to March 2012. The fatigue pictogram was used
to evaluate the level of fatigue interference in the daily life activities of
kidney transplant patients. The sample consists of 39 patients, and was developed
in 2 phases: data collection and attendance after and before the transplantation
until hospital discharge. Descriptive statistical analyses were used. In the
group at issue, we have noticed the following profile of the sample: 84.3% of
transplantations with live donors, most were men, average age 36.5 years old,
average hospitalization time 11.1 days, average time of renal failure 66.4
months, systemic arterial hypertension prevalence 66.7%, and the prevalence of at
least 1.8 diseases in each individual. The self-referred causes of chronic renal
failure were uncontrolled systemic arterial hypertension, glomerulonephritis, and
overuse of anti-inflammatory drugs, among others. The study shows that fatigue is
directly related to the level of activities of daily living, causing less ability
to perform activities in the higher level of fatigue, which is in the immediate
postoperative period and only settling fully on the 9th postoperative day.
PMID- 25131027
TI - Body mass index in the first year after kidney transplantation.
AB - INTRODUCTION: Kidney transplant recipients (KTR) experience better appetite,
partly due to the use of steroids, and are subjected to less severe dietetic
restrictions, hence they tend to increase the uptake of calories, which favors
weight gain posttransplantation. In this study, we evaluate the profile of body
mass index (BMI) in the first year posttransplantation. METHODS: This was a
retrospective study including 131 patients who received transplants between 1991
and 2011. We collected demographic and clinical data such as body weight and
height, and calculated BMI pretransplantation and at 6 and 12 months
posttransplantation. RESULTS: Mean age was 47.1 +/- 13.1 years, 64.9% were male,
and 29% of patients were diabetic. Pretransplantation mean BMI was 23.04 +/- 4.08
kg/m(2), and at 6 and 12 months posttransplantation it increased to 24.55 +/- 4.2
kg/m(2) and 24.65 +/- 4.16 kg/m(2), respectively (P < .001). At 6 months, this
significant weight gain occurred in all patients, even those malnourished,
eutrophic, overweight, and obese at pretransplantation. Looking at
pretransplantation malnourished patients, 30.8% remained malnourished 1 year
after transplantation. Otherwise, 28.6% of pretransplantation overweight patients
and 100% of pretransplantation obese patients could be classified as obese at 1
year posttransplantation. CONCLUSIONS: Increase in BMI is common in obese and
nonobese KTR. This study highlights the importance of identifying subjects at
risk for excessive weight gain posttransplantation, thus allowing an early
nutritional intervention to prevent its complications.
PMID- 25131028
TI - Outcome of bacteremia caused by extended-spectrum beta-lactamase-producing
Enterobacteriaceae after solid organ transplantation.
AB - INTRODUCTION: Although infection with extended-spectrum beta-lactamase-producing
Enterobacteriaceae (ESBL-E) has been recognized as an important cause of
morbidity after solid organ transplantation, there are limited data on the
outcome of this complication among transplant recipients. The objective of this
study was to describe the outcome and factors associated with mortality among
recipients of abdominal solid organ transplants with bloodstream infection caused
by ESBL-E. PATIENTS AND METHODS: This study was a retrospective analysis of a
case series of patients who had bacteremia caused by ESBL-E after undergoing
renal or liver transplantation between January 2000 and September 2008 at a
university-affiliated hospital in Rio de Janeiro, Brazil. The primary end point
of the study was death within 30 days of the diagnosis of bacteremia. RESULTS:
During the study period, 997 subjects underwent kidney (759 patients) or liver
(238 patients) transplantation. Fifty-four episodes of bacteremia caused by ESBL
E were diagnosed in 39 patients (4%). Mortality after the first episode of ESBL-E
bacteremia was 26% (10 deaths). In multiple logistic regression analysis, the
Pitt bacteremia score (P = .005) and being on mechanical ventilation at the time
of infection diagnosis (P = .02) were the only variables associated with
mortality. Thirteen episodes of recurrent bacteremia occurred in 8 (28%) of the
29 patients who survived the first episode. Two (25%) of these 8 patients died
during the course of a recurrent episode. CONCLUSIONS: Bacteremia caused by ESBL
E was associated with high mortality and high risk of recurrence. Factors
associated with clinical severity at the time of infection diagnosis were the
main predictors of mortality.
PMID- 25131029
TI - Urinary tract infection in renal transplant recipients: incidence, risk factors,
and impact on graft function.
AB - INTRODUCTION: Urinary tract infection (UTI) is the most common infection
posttransplant. However, the risk factors for and the impact of UTIs remain
controversial. The aim of this study was to identify the incidence of
posttransplant UTIs in a series of renal transplant recipients from deceased
donors. Secondary objectives were to identify: (1) the most frequent infectious
agents; (2) risk factors related to donor; (3) risk factors related to
recipients; and (4) impact of UTI on graft function. PATIENTS AND METHODS: This
was a retrospective analysis of medical records from renal transplant patients
from January to December 2010. Local ethics committee approved the protocol.
RESULTS: The incidence of UTI in this series was 34.2%. Risk factors for UTI were
older age, (independent of gender), biopsy-proven acute rejection episodes, and
kidneys from deceased donors (United Network for Organ Sharing criteria). For
female patients, the number of pretransplant pregnancies was an additional risk
factor. Recurrent UTI was observed in 44% of patients from the UTI group. The
most common infectious agents were Escherichia coli and Klebsiella pneumoniae,
for both isolated and recurrent UTI. No difference in renal graft function or
immunosuppressive therapy was observed between groups after the 1-year follow-up.
CONCLUSIONS: In this series, older age, previous pregnancy, kidneys from expanded
criteria donors, and biopsy-proven acute rejection episodes were risk factors for
posttransplant UTI. Recurrence of UTI was observed in 44%, with no negative
impact on graft function or survival.
PMID- 25131030
TI - MELD score and albumin replacement are related to higher costs during management
of patients with refractory ascites.
AB - BACKGROUND: Ascites is the most common complication of cirrhosis and indicates
that the disease is at an advanced stage. In cirrhotic patients with refractory
ascites, treatment is based on repeat paracentesis. The objective of this study
is to evaluate the cost of paracentesis in cirrhotic patients and to determine
the factors related to this cost. METHODS: This prospective study included all
patients with cirrhosis who underwent paracentesis between March 2012 and March
2013 at the Outpatient Service of the Liver Transplantation Unit, Clinical
Hospital, University of Sao Paulo School of Medicine. Microcost analysis was
performed with individual tabbed data regarding the consumption of albumin and
containers for ascites. The remaining cost components were drugs, materials used
during the procedure, and human resources. Statistical analysis was performed
using SPSS version 20. RESULTS: We conducted a total of 881 paracentesis
procedures in a group of 155 patients that included 60.5% men and 39.5% women
with a mean age of 57 years (range 20 to 80 years). Patients underwent an average
of 5.3 paracentesis procedures per year (range 1 to 32). The total cost of all
procedures was $193,126.60 and the most costly component was albumin
($87,162.10). The average cost per procedure was $219.50. The most frequent liver
disease diagnoses were hepatitis C (24%) and alcoholic cirrhosis (24%). The
majority of patients were on the liver transplant list (54.2%). Factors
associated with higher costs in the period were a Model for End-Stage Liver
Disease score higher than 24 (P = .001) and patients on the transplant waiting
list (P = .042). CONCLUSIONS: Paracentesis in cirrhotic patients is a high-cost
procedure in health care. The main factors related to cost are the volume of
fluid drained due to the need for albumin replacement and the severity of liver
disease that is related to the frequency of paracentesis.
PMID- 25131031
TI - Liver transplantation for unresectable hepatocellular carcinoma in elderly
patients: what to expect.
AB - INTRODUCTION: Elderly patients have orthotopic liver transplantation (OLT)
outcomes comparable to younger individuals. However, it is undefined whether such
results are also seen in those with unresectable hepatocellular carcinoma (HCC).
The primary endpoints of this study were overall survival (OS), retransplantation
rate, and disease-free survival (DFS) in OLT recipients with HCC and aged >=65
years compared with those aged <65 years. PATIENTS AND METHODS: This was a single
center retrospective review of a cohort of adult deceased-donor OLT recipients
due to unresectable HCC within the Milan criteria from May 2006 through March
2013. Demographic and clinical variables and outcomes of patients aged >=65 years
were compared with those aged <65 years. RESULTS: Thirty-seven individuals >=65
years of age (group 1) and 141 individuals <65 years of age (group 2) were
analyzed. OS (group 1 vs group 2) at 1 year (78% vs 81%), 3 years (64% vs 70%),
and 5 years (64% vs 66%) (P = .49) was comparable. Retransplantation rates were
also similar (group 1: 13.5%; group 2, 10.6% [P = .61]). DFS (group 1 vs group 2)
at 1 year (100% vs 95%), 3 years (91% vs 92%), and 5 years (91% vs 92%) (P = .56)
was also not significantly different between groups. On multivariate analysis,
age >65 years was not an independent predictor of OS or DFS. CONCLUSIONS:
Patients aged >=65 years with HCC presented with outcomes similar to their
younger counterparts. Chronologic age is not a good predictor of outcome, and
transplantation is feasible if overall clinical conditions and comorbidities
allow.
PMID- 25131032
TI - Surface electromyography for respiratory assessment of liver transplant
candidates, healthy subjects and after chevron post-operative incision.
AB - BACKGROUND: Surface electromyography is a noninvasive technique for detecting the
activity of skeletal muscles and especially the muscles for respiratory
compliance; namely, the diaphragm and rectus abdominis. This study compares these
muscles in healthy individuals, liver disease patients, and after abdominal
surgery. OBJECTIVE: To study muscle activity by surface electromyography of the
right diaphragm muscles and right rectus abdominis (root means square, RMS), and
the manovacuometry muscle strength (maximal inspiratory pressure, MIP; and
maximal expiratory pressure, MEP). RESULTS: We evaluated 246 subjects who were
divided into 3 groups: healthy (65), liver disease (171), and post-surgery (10).
In liver disease group the BMI was higher significantly for ascites (P = .001),
and was increase in RMS rectum (P = .0001), RMS diaphragm (P = .030), and a
decreased inspiratory and expiratory indices (P = .0001) pressure in the post
surgery group. A multivariate analysis showed tendency to an increased BMI in
liver disease and in the post-surgery groups correlated with an increased RMS
rectum and the lower MIP/MEP (P = .11). The receiver operating characteristic
curve showed that RMS rectus was capable of discriminating liver disease and post
surgery patients from healthy subjects (area = 0.63; 95% CI 0.549-0.725).
CONCLUSION: The muscle activity of normal individuals is lower than in subjects
with deficit muscles because less effort is necessary to overcome the same
resistance, observed by surface electromyography and muscle strength.
PMID- 25131033
TI - Evaluation of functional status, pulmonary capacity, body composition, and
quality of life of end-stage liver disease patients who are candidates for liver
surgery.
AB - INTRODUCTION: Muscular weakness in combination with malnutrition can induce a
global motor impairment and physical inactivity, adversely impairing the daily
living activities and quality of life of end-stage liver disease patients who are
candidates for liver transplantation. OBJECTIVES: To evaluate functional status,
pulmonary capacity, body composition and quality of life in end-stage liver
disease patients who are candidates for liver transplantation; to verify if there
is a correlation between the functional variables of the individuals tested
through the 6-minute walk test (6MWT) and covariables: pulmonary function test
(PFP), quality of life and body composition. METHODS: This study was carried out
at the Liver Transplantation Unit of the State University of Campinas (UNICAMP).
We included 46 patients with end-stage liver disease who underwent the following
evaluations: medical history, quality of life questionnaire "Short Form 36" (SF
36), surface electromyography (sEMG) of the diaphragm and rectus abdominis
muscles, body composition assessment by electrical vioimpedance (BIA), 6MWT and
PFP. RESULTS: Univariate analysis and Pearson's correlation found correlations
between distance walked on 6MWT and QOL (P = .006 and P = .02) and TBW (P = .5
and P = .02). Pearson's correlation were found between respiratory variables of
6MWT, QOL, and PFP. CONCLUSION: The functional status may be correlated to body
composition, quality of life and pulmonary capacity of patients with liver
disease, candidates for transplantation.
PMID- 25131034
TI - Effects of a respiratory physiotherapeutic program in liver transplantation
candidates.
AB - BACKGROUND: Candidates for liver transplantation may have malnutrition, fatigue,
loss of muscle mass and function. The combination of these factors leads to
overall physical disability and physical inactivity. OBJECTIVE: The aim of the
study was to evaluate the effects of a respiratory physiotherapeutic program on
liver transplantation candidates. METHOD: Forty-two patients were evaluated by
respiratory muscle strength, surface electromyography of the rectus abdominis and
diaphragm, and spirometry. We also applied the SF-36. The patients were divided
into two groups: 12 randomly assigned to the control group and 5 in the
intervention group. The intervention consisted of an explanatory and illustrative
manual to be followed at home with diaphragmatic breathing exercises,
diaphragmatic isometric exercise, Threshold IMT, lifting the upper limbs with a
bat, and strengthening the abdominals. RESULTS: Significant difference was found
between initial forced expiratory flow (FEF)25-75% (P = .042) and final FEF25-75
in the intervention group. The control group had significant difference (P =
.036) in the diaphragm RMS between initial time and end time. In conclusion, the
control group showed greater electrical activity of the diaphragm after 3 months.
CONCLUSION: The intervention group benefited from the exercise, thus improving
the FEF25-75%.
PMID- 25131035
TI - Clinical evaluation of hepatic transection on pediatric liver transplantation.
AB - OBJECTIVES: Liver transplantation is an effective technique in the treatment of
end-stage liver disease. The aim of this study was to evaluate the impact of
hepatic transection, an advanced surgical technique able to tailor size to
generate two grafts to from a single donor. MATERIALS AND METHODS: A
retrospective study between January 2000 and September 2013, reviewing 91
pediatric patients who underwent 96 liver transplants from deceased donors.
Patients were distributed into two groups: whole organ (WO, n = 39) and
transected liver grafts (TLG, n = 57). The following were evaluated: etiology,
anthrophometric parameters (age, weight, height, z score weight/age, and
height/age), model for end-stage liver disease (MELD) or pediatric end-stage
liver disease (PELD), previous surgeries, transfusion of blood components, 1-year
survival rate, preoperative laboratory testing, from the second and seventh
postoperative days, lactate during surgery, postoperative complications, duration
of surgery, duration of cold and warm ischemia, types of biliary reconstruction,
and laboratory testing of the donor. RESULTS: The anthropometric values showed
significant differences (P < .05) between the groups. The average age was 124.7
months in the WO group and 33.6 months in the TLG group (P < .0001), while the
weight was 28.0 kg and 7.4 kg, respectively (P < .0001). The analysis of z score
weight/age showed that the TLG had greater acute and chronic malnutrition,
probably due to the etiology of liver disease, present from birth in patients as
young. Red blood transfusion was higher in the TLG group (P < .0006) due to the
cut surface of the graft, emphasizing the use and improvement of hemostatic
techniques. CONCLUSION: Despite differences between the groups, clinical and
surgical complications were similar, showing that liver transection injury didn't
change the results of transplantation. There was no impact on liver function,
graft, or 1-year patient survival after liver transection. Second postoperative
lactate is a predictive factor of death. Transection liver transplantation is an
effective method as an alternative to pediatric liver transplantation.
PMID- 25131036
TI - Grade IV fibrosis interferes in biliary drainage after Kasai procedure.
AB - OBJECTIVES: Biliary atresia (BA) is the most common cause of liver
transplantation in children. The earlier the treatment is done, the better the
prognosis. The aim is to evaluate the impact of late diagnosis in children with
BA, including the histopathological findings and success rate of biliary drainage
in patients submitted to hepatic portoenterostomy (HPE). MATERIALS AND METHODS: A
retrospective study of cases of BA in the Department of Pediatric Surgery,
Federal University of Sao Paulo (UNIFESP) between 1998-2011. We found 63 cases of
BA; of these, 42 underwent HPE and 21 were referred for liver transplantation.
Clinic and pathologic data were evaluated. RESULTS: The HPE was performed with a
mean age of 86.5 days, with 16.6% having the operation at 60 days or earlier;
59.2% between 61 and 90 days; and 23.8% after 90 days. Successful biliary
drainage occurred in 31% of surgeries, Mean days when HPE drained was 69.1 days,
and 94.3 days when the surgery did not drain (P = .05). All patients who were
successfully drained, did not have grade IV fibrosis on histology. In cases in
which surgery was performed after 60 days that had not drained, 25% had grade IV
fibrosis on biopsy (P = .0469). CONCLUSION: The age of HPE relates to better
prognosis of the disease. It was found that the rate of grade IV fibrosis is
higher in no drainage patients. All patients with grade IV fibrosis had no
biliary drainage.
PMID- 25131037
TI - Comparative morphometric analysis of 5 interpositional arterial autograft options
for adult living donor liver transplantation.
AB - In living donor liver transplantation, the right-sided graft presents thin and
short vessels, bringing forward a more difficult anastomosis. In these cases, an
interpositional arterial autograft can be used to favor the performance of the
arterial anastomosis, making the procedure easier and avoiding surgical
complications. OBJECTIVE: We compared the inferior mesenteric artery (IMA), the
splenic artery (SA), the inferior epigastric artery (IEA), the descending branch
of the lateral circumflex femoral artery (LCFA), and the proper hepatic artery
(PHA) as options for interpositional autograft in living donor liver
transplantation. METHOD: Segments of at least 3 cm of all 5 arteries were
harvested from 16 fresh adult cadavers from both genders through standardized
dissection. The analyzed measures were proximal and distal diameter and length.
The proximal diameter of the RHA and the distal diameter of the SA, IMA, IEA and
the LCFA were compared to the distal diameter of the RHA. The proximal and distal
diameters of the SA, IEA and LCFA were compared to study caliber gain of each
artery. RESULTS: All arteries except the IMA showed statistical significant
difference in relation to the RHA in terms of diameter. Regarding caliber gain,
the arteries demonstrated statistical significant difference. All the harvested
arteries except PHA were 3 cm in length. CONCLUSION: The IMA demonstrated the
best compatibility with the RHA in terms of diameter and showed sufficient length
to be employed as interpositional graft. The PHA, the SA, the IEA and the LCFA
presented statistically significant different diameters when compared to the RHA.
Among these vessels, only the PHA did not show sufficient mean length.
PMID- 25131038
TI - Is there a relationship between intraoperative hemodynamic instability and
calcineurin inhibitor-related toxicity, early after liver transplantation? A
single-center observational study.
AB - This study evaluated the relationship between intraoperative hemodynamic
instability (IOHI) and the development of calcineurin inhibitor (CNI) toxicity in
the early postoperative period after liver transplantation (LT). Eighty-two
patients were enrolled during a 1-year period and a 3-month follow-up. IOHI,
requiring continuous infusion of vasopressors, was observed in 31 patients (38%,
group 1; control group 2, n = 51). Acute kidney injury (AKI) developed in 28
patients (52% in group 1 vs 24% in group 2, P = .02), and CNI-related
neurotoxicity (CNI-NT) in 26 (48% in group 1 vs 22% in group 2, P = .03). Group 1
patients received mainly deceased donor grafts (87% vs 57% in group 2, P < .001).
An independent association between IOHI and CNI-NT (P = .029) and AKI (P = .016)
was observed. The receiver-operator characteristic curve revealed an area under
the curve of 0.63 for IHI (sensitivity 56%; specificity 75%) and 0.65 for AKI
(sensitivity 56%; specificity 70.2%). In conclusion, patients undergoing LT with
IOHI may be more prone to developing CNI-NT and AKI in the early postoperative
period.
PMID- 25131039
TI - Ten-year experience with liver transplantation for hepatocellular carcinoma in a
Federal University Hospital in the Northeast of Brazil.
AB - Hepatocellular carcinoma (HCC) is the most frequent and important primary liver
tumor, with annual worldwide incidence of over 1 million cases, accounting for at
least 500,000 deaths per year. The majority of cases of HCC occur in the setting
of liver cirrhosis. In this retrospective, descriptive, and analytical study,
between May 2002 and April 2012, 664 liver transplantations (LT) were conducted
at a Federal University Hospital in the Northeast of Brazil, among which 140 LT
were performed in patients with HCC. The tumor was more frequent in men with an
average age of 56 years and infected with hepatitis C virus, many with a history
of alcohol abuse. Alpha-fetoprotein was not useful in the diagnosis, and imaging
methods have failed to diagnose the nodules in 19 patients (13.6%). Transarterial
chemoembolization was the most-used bridging therapy to inhibit tumor growth for
patients with HCC eligible for transplantation. The implementation of the Model
for End Stage Liver Disease score in 2006 brought benefits to these patients. The
rate of HCC recurrence after LT was 8.57% and occurred more often in the first 2
years after transplantation, with the liver graft being the most common site.
Significant risk factors for recurrence were a long time on the LT waiting list,
number of liver nodules over 3.5, and the presence of vascular invasion. In
conclusion, LT for HCC leads to excellent long-term survival, with relatively few
patients dying from tumor recurrence.
PMID- 25131040
TI - Response to transarterial chemoembolization in candidates with hepatocellular
carcinoma within Milan criteria does not predict post-transplant disease-free
survival.
AB - INTRODUCTION: Few groups have studied the impact of pretransplant transarterial
chemoembolization (TACE) in the outcomes of liver transplant recipients with
hepatocellular carcinoma (HCC). We verified whether response to TACE in HCC
candidates impacts post-transplant disease-free survival. METHODS: This a single
center retrospective study of patients who underwent liver transplantation from
2006-2013. Included were those transplanted due to HCC within the Milan criteria
who were treated with TACE in the pre-transplant period. Response to TACE
followed the modified RECIST (mRECIST) criteria. Disease free-survival was the
main endpoint of the study. RESULTS: We included 187 patients in this study. The
population had an average age of 57.5 years, predominantly formed by men (82.5%),
with an average IMC of 26.7, MELD of 13, with viral hepatitis as main cause of
liver disease. Average waiting time was 253 days and follow-up was 27.3 months.
Based on response to TACE, 3-year disease-free survival was 84.1% for those with
complete response to TACE, 84.1% for those with partial response to TACE, 85.7%
for those with stable disease and 100% for patients with progressive disease.
Multivariate analysis did not identify response to TACE as a predictor of disease
free post-transplant survival. CONCLUSIONS: Response to TACE in candidates with
HCC within Milan criteria does not predict post-transplant disease-free survival.
PMID- 25131041
TI - Results from a liver transplant center in northeastern Brazil that performed more
than 100 transplants in 2011.
AB - BACKGROUND: Orthotopic liver transplantation is an essential approach performed
in several centers around the world. Our center lies in northeastern Brazil and
has performed this procedure since 2002. In 2011, 126 liver transplants were
performed at our institution. METHODS: This study is a retrospective and
descriptive analysis of the data collected from the medical records of those
transplants. Epidemiological and clinical aspects were considered in this
evaluation. The outcome analysis considered overall survival rates within 30 days
and 1 year after transplantation. RESULTS: The sample of 124 patients showed 60%
of all patients came from other regions, particularly the North and Midwest
regions of Brazil, which had a combined population of >30 million in 2011. The
most frequent etiologies for end-stage liver disease were hepatitis C and
alcoholism. The average calculated MELD (Model for end-stage liver disease) was
21.0. Patient survival curves were 88.4% after 30 days and 81.5% after 1 year.
CONCLUSION: The development of effective perioperative management for this
procedure resulted in improved outcomes. Our center's performance is based on a
multidisciplinary approach performed by qualified personnel, careful pre- and
postoperative follow-up and continuous improvement of services.
PMID- 25131042
TI - Effect of a physical exercise program on the functional capacity of liver
transplant patients.
AB - BACKGROUND: Recently there has been great concern about the quality of life and
health of liver transplant patients (LTP). These patients often present with
metabolic disorders, which can improve with regular physical exercise. The aim of
this study was to investigate the effect of a physical exercise program on the
functional capacity of LTP. METHOD: The distance walked in the 6-minute walk test
and the resting energy expenditure (REE) were evaluated in 15 subjects who
regularly attend the outpatient Bias Fortes Clinic at Universidade Federal de
Minas Gerais. The patients were divided into 2 groups, the Exercise Group (EG) (6
men and 3 women; 52 +/- 15 years old, BMI 22.4 +/- 4.0 kg/m2) performed 24
sessions of continuous 30 min treadmill exercise. Intensity of exercise was
increased from 50%-70% of the maximum heart rate over the training period. A
group of 3 men and 3 women (39 +/- 15 years, BMI 24.5 +/- 4.4 kg/m2) served as
controls (CG). RESULTS: After undergoing exercise training, patients in the EG
showed a 19.4% increase in the distance walked (pre = 453.6 +/- 128.0 m and post
= 582.5 +/- 90.1 m). Also, there was an increase in their REE (pre = 1,060.0 +/-
194.2 kcal and post = 1,375.0 +/- 258.6 kcal) (P < .05) indicating an increase in
their exercise capacity and metabolic improvements. There were no differences in
the distance walked (pre = 516.5 +/- 62.0 m and post = 517.7 +/- 71.9 m) and REE
(pre = 1,393.0 +/- 213.3 kcal to post = 1,465.0 +/- 170.3 kcal) (P > .05) for CG.
Our results are in agreement with previous studies. CONCLUSIONS: We conclude that
the exercise program promoted significant improvements in functional capacity.
These findings have positive implications for the control of metabolic diseases,
which are common in patients after liver transplantation.
PMID- 25131043
TI - Use of IGL-1 preservation solution in liver transplantation.
AB - University of Wisconsin (UW) solution has been known as the standard solution for
liver graft preservation. Alternative preservation solutions have been used in
liver transplantation, such as histidine-tryptophan-ketoglutarate (HTK) and
Celsior solution. Institut Georges Lopez-1 (IGL-1) is a new preservation solution
with lower potassium and lower viscosity than UW solution that has recently been
used in liver transplant. Data from 178 patients who received transplants from
August 2008 to June 2013 at Hospital Santa Isabel, Blumenau, Brazil, were
analyzed. All patients received grafts from brain death donors. In November 2011
we started to use IGL-1 as an alternate preservation solution. Therefore, 53
patients using IGL-1 preserved grafts were compared to 125 using HTK solution.
The donor age in the HTK group ranged from 11-77 years, with a mean of 43.4 +/-
4.8. In the IGL-1 group donor age ranged from 9-62 years, with a mean of 35.8 +/-
4.5. Cold ischemia time in the HTK group ranged from 85-1145 minutes, mean 443.5
+/- 183.5 minutes. In the IGL-1 group, cold ischemia time ranged from 85-670
minutes, mean 329.3 +/- 134.8 minutes. The overall operative mortality rate was
14% (25 patients); in the HTK group, 14.4% (18 patients); and in the IGL-1 group,
13.4% (7 patients). One graft in the HTK group presented with primary non
function (PNF), 0.7%; there were none in the IGL-1 group. In our study, IGL-1 has
been shown to be safe to use as a preservation solution for liver
transplantation. Early post-transplant graft function was comparable to that
observed with HTK solution, although a tendency for lower alanine
aminotransferase levels was noticed. IGL-1 has been shown to be safe, cost
efficient, and an effective preservation solution.
PMID- 25131044
TI - Is urinary gamma-glutamyl transpeptidase superior to urinary neutrophil
gelatinase-associated lipocalin for early prediction of acute kidney injury after
liver transplantation?
AB - In this prospective study, we comparatively evaluated the accuracy of several
biomarkers of acute kidney injury (AKI) on predicting its occurrence after liver
transplantation (LT). The parameters evaluated were urinary tubular enzymes
(gamma-glutamyl transpeptidase [gammaGT], alkaline phosphatase, and urinary
lactate dehydrogenase) and urinary neutrophil gelatinase-associated lipocalin.
These parameters were evaluated both as isolated variables and divided by urinary
creatinine. Samples were collected by the end of surgery (determination 1) and at
12 to 24 hours after surgery (determination 2). The study endpoint was the
development of AKI. The study was performed over a 1-year period, and 61 of 77
patients were enrolled (main exclusion criteria were perioperative death,
previous known renal failure, and insufficient data for analysis). Of these 61
patients, AKI was observed in 19 (group 1). The main relevant parameter to
predict AKI was the absolute value of urinary gammaGT at determination 1 (area
under the curve, 0.74; specificity, 72.5%; sensitivity, 70.3%; cutoff, 36 U/mL).
Urinary neutrophil gelatinase-associated lipocalin was not as accurate; the best
predicted value for this parameter was absolute value at D1 with an area under
the curve of 0.5 (specificity, 84.2%; sensitivity, 35.7%; cutoff value, 44.6
ng/mL). We concluded that the absolute value of urinary gammaGT evaluated at the
end of LT was the most accurate parameter to predict AKI in our cohort. Urinary
enzyme levels must be taken into account in future analysis of this issue.
PMID- 25131045
TI - Acute kidney injury after liver transplantation: incidence and mortality.
AB - INTRODUCTION: Patients undergoing orthotopic liver transplantation often present
with acute kidney injury (AKI) in the postoperative period. It has been
associated with a greater number of complications and high mortality rates. The
goal of this study was to determine the incidence of AKI during the early
posttransplant period and mortality in patients undergoing orthotopic liver
transplantation in our hospital. PATIENTS AND METHODS: In this retrospective
cohort study, we reviewed the medical records of all patients aged >18 years
undergoing liver transplantation from April 2008 to April 2011. The exclusion
criteria were a glomerular filtration rate (estimated by using the Modification
of Diet in Renal Disease formula) <60 mL/min/1.73 m(2) or AKI at the time of
transplantation. AKI was defined as an increase >=50% from preoperative baseline
serum creatinine levels during the hospitalization period. RESULTS: Of 113
selected patients, 78 (69%) were male. The mean age was 54.03 +/- 9.38 years. The
mean preoperative baseline creatinine level was 0.94 +/- 0.15 mg/dL, and the
estimated glomerular filtration rate was 87.09 +/- 19.67 mL/min/1.73 m(2). The
mean calculated Model for End-Stage Liver Disease score was 13. Hepatitis C
serology was present in 70.8%, hepatitis B in 11.5%, hepatocellular carcinoma in
75.2%, and alcohol abuse in 31.9% of patients. The incidence of AKI was 56.6% (64
of 113 patients). The main risk factors for AKI were Model for End-Stage Liver
Disease score and diuretic use at baseline. Renal replacement therapy (RRT) was
performed in 19.5% (22 of 113) of patients. The hospital mortality rate in the
group with AKI was 25% (16 of 64 patients) and 6.1% (3 of 49 patients) between
patients without AKI (odds ratio, 5.11 [confidence interval, 1.39-18.7]; P <
.01]. Among patients who underwent RRT, the in-hospital mortality rate was 54.5%
(12 of 22 patients) compared with 7.7% (7 of 91 patients) from the other
remaining patient cohort (odds ratio, 14.40 [confidence interval, 4.60-45.00]; P
< .01). CONCLUSIONS: There was a high incidence of AKI in patients undergoing
liver transplantation and an increased risk of mortality among patients who
needed RRT.
PMID- 25131046
TI - Relevance of anxiety and stress levels on sleep quality after liver
transplantation.
AB - The goal of this study was to assess the effects of anxiety and stress on sleep
quality in liver transplantation recipients. A prospective cross-sectional study
was performed including 45 recipients enrolled at a liver transplantation program
at Ribeirao Preto, State of Sao Paulo, Brazil. Anxiety and stress were evaluated
by using a reduced version of the State-Trait Anxiety Inventory and the Perceived
Stress Scale, respectively. Sleep quality and excessive daytime sleepiness were
evaluated by using the Brazilian Portuguese versions of the Pittsburgh Sleep
Quality Index and the Epworth Sleepiness Scale. Thirty-two (71.11%) recipients
presented with compromised sleep quality and 5 (11.11%) presented with excessive
daytime sleepiness. Recipients with bad sleep quality had anxiety (mean, 26.91
points) and stress (mean, 17.88 points) levels that were higher than the levels
of patients with normal sleep quality patterns, with anxiety levels presenting
with statistically significant differences (P = .0420). Patients with above
average stress levels also had increased anxiety (mean, 28 points) and
compromised sleep quality (mean, 7.03 points). In conclusion, a liver
transplantation recipient who experiences bad sleep quality also has higher
levels of anxiety and stress, suggesting a relationship between the sleep
wakefulness cycle and anxiety/stress. Planning strategies aimed at reducing such
emotional shifts among recipients is of paramount importance. Therefore, new
strategies focusing on improving the sleep pattern of patients are necessary
because unhealthy sleep behavior may impair postoperative recovery.
PMID- 25131047
TI - Risk factors of pancreatic graft loss and death of receptor after simultaneous
pancreas/kidney transplantation.
AB - Simultaneous pancreas/kidney transplants require a long graft survival and the
recipient to present with more benefits than risks. We evaluated the risk factors
of receptor's death and pancreatic graft loss on 2 occasions (3 and 12 months'
postoperatively) in 292 transplants in whom 22 variables were evaluated.
Variables were selected, 9 receivers, 8 donors, and 5 variables related to the
surgical procedure. All independent variables were compared with the dependent
variables of pancreatic graft losses and patient deaths. Those considered
significant according to univariate analysis were analyzed by using multiple
logistic regression techniques in an attempt to develop a mathematical model
capable of predicting both pancreatic graft and patient losses. Lastly, based on
the resulting models with all significant variables, scores were created to
determine the risk of patient death and pancreatic graft loss. In the adjusted
multivariate analysis, the significant variables were donor age, receiver's body
mass index, initial pancreas implant, iliac venous drainage, and use of induction
therapy related to pancreatic loss within 3 months after transplantation.
Independent risk factors regarding the loss of patients within 12 months were
body mass index and receptor induction therapy. The variables related to
pancreatic graft loss within 3 months were donor age, receiver body mass index,
initial use of pancreatic graft, iliac venous drainage, and induction therapy;
these variables can be used for creating a risk score. The donor body mass index
and the induction therapy were independently related to patient loss within 12
months after the transplant.
PMID- 25131048
TI - Component analysis of hospital cost of pancreas-kidney transplant and
correlations with different variables in a Brazilian hospital.
AB - INTRODUCTION: Simultaneous pancreas-kidney transplantation is associated with a
high rate of complications when it is compared with transplantation of other
organs; these increased complications can result in increased financial costs of
the procedure. The objective of this study was to determine operating costs and
financial results of simultaneous pancreas-kidney transplantation and its
different variables in a Brazilian hospital. PATIENTS AND METHODS: Between
January 2008 and December 2011, the monthly costs of 105 patients were
calculated. These patients were divided into 2 groups; the first consecutive 53
patients were labeled group I and the second set of 52 patients were labeled
group II. The cost evaluation was made in US dollars. RESULTS: A total of 89
patients corresponded to the public health system and 16 patients to the
supplementary health system. The percentage of hospital discharge was 92.4%.
There was an increase in operating room costs in group II compared with group I
with no statistically significant difference ($18,749.33 for group I and
$17,608.26 for group II). The outcome of the operation was positive; it was
greater for group II than for group I ($16,303.22 vs $3494.53). CONCLUSIONS:
Simultaneous pancreas-kidney transplantation is a financially feasible procedure
in Brazil, with the public health system being the main payment source.
PMID- 25131049
TI - Home parenteral nutrition program and referral of potential candidates for
intestinal and multivisceral transplantation in a single Brazilian center.
AB - Intestinal failure is a multifaceted condition that may require high-complexity
treatment and a multidisciplinary program, including home parenteral nutrition
therapy (HPNT) and intestinal transplantation. In this article, we profile a
Brazilian single-center experience with 128 cases of HTPN followed for the last
30 years and appraise the referral for potential intestinal and multivisceral
transplantation.
PMID- 25131050
TI - Heart transplantation in pediatric population and in adults with congenital heart
disease: long-term follow-up, critical clinical analysis, and perspective for the
future.
AB - BACKGROUND: Heart transplantation is a treatment option for children as well as
for adults with congenital heart disease. OBJECTIVE: To report the experience of
a tertiary center with heart transplant program in pediatric population and in
adults with congenital heart disease. PATIENTS AND METHODS: The study consisted
of the evaluation of pediatric as well as adult patients undergoing heart
transplantation for congenital heart disease. We evaluated the following
indication and complications such as renal dialysis, graft vascular disease,
tumors and survival. RESULTS: From October 1992 to November 2013, 134 patients
had transplantation, and there were 139 transplantations and 5
retransplantations. The immunosuppression regimen is based on calcineurin
inhibitors and cytostatic drugs. The type of heart disease indicated for
transplantation was cardiomyopathies in 70% and congenital heart disease in 30%.
Of these 134 patients, 85 patients were alive. Actuarial survival is 77.4%,
69.6%, 59.3% at 1, 5, and 10 years after transplantation. Three patients
underwent renal transplantation, 1 patient is in renal dialysis, and 8.2% of
patients had post-transplant lymphoproliferative disease. Two patients had
retransplantation for graft vascular disease; 1 of them required a simultaneous
kidney transplant and died 30 days after the procedure and 1 patient is
clinically well 2 years after retransplantation. CONCLUSION: Heart
transplantation in children and in adults with congenital heart disease is a
promising therapeutic option and enables long-term survival for these patients.
PMID- 25131051
TI - Posterior reversible encephalopathy syndrome in lung transplantation: 5 case
reports.
AB - Posterior reversible encephalopathy syndrome (PRES) is a cliniconeuroradiologic
entity characterized by typical neurologic symptoms with characteristic cerebral
image alterations. It has been reported in solid organ transplantations,
especially related to the use of calcineurin inhibitors. The incidence of PRES in
lung transplantation is unknown and probably under-reported in the literature.
Here we describe 5 cases of PRES after bilateral lung transplantation. One of the
reported cases was the first in the literature in which the neurologic onset
precluded the introduction of calcineurin inhibitor. Therefore, although
calcineurin inhibitors are known to play an important role in the development of
PRES in the setting of lung transplantation, other causes seems to be involved in
the physiopathology of this syndrome.
PMID- 25131052
TI - Fungal infection by Mucorales order in lung transplantation: 4 case reports.
AB - Mucorales is a fungus that causes systemic, highly lethal infections in
immunocompromised patients. The overall mortality of pulmonary mucormycosis can
reach 95%. This work is a review of medical records of 200 lung transplant
recipients between the years of 2003 and 2013, in order to identify the
prevalence of Mucorales in the Lung Transplantation service of Heart Institute
(InCor), Hospital das Clinicas da Universidade de Sao Paulo, Brazil, by culture
results from bronchoalveolar lavage and necropsy findings. We report 4 cases
found at this analyses: 3 in patients with cystic fibrosis and 1 in a patient
with bronchiectasis due to Kartagener syndrome. There were 2 unfavorable outcomes
related to the presence of Mucorales, 1 by reduction of immunosuppression,
another by invasive infection. Another patient died from renal and septic
complications from another etiology. One patient was diagnosed at autopsy just 5
days after lung transplantation, with the Mucor inside the pulmonary vein with a
precise, well-defined involvement only of donor's segment, leading to previous
colonization hypothesis. There are few case reports of Mucorales infection in
lung transplantation in the literature. Surveillance for the presence of Mucor
can lead to timely fungal treatment and reduce morbidity and mortality in the
immunocompromised patients, especially lung transplant recipients.
PMID- 25131053
TI - Cardiac effect of ischemic preconditioning and heparin following intestinal
ischemia and reperfusion in rats.
AB - To study the role of heparin and ischemic preconditioning (IPC) in cardiac injury
after intestinal ischemia (I) and reperfusion (R), 54 rats underwent 60 minutes
of I, which was produced by occlusion of the superior mesenteric artery, and/or
120 minutes of R. The IPC group had the I procedure stimulation for 5 minutes and
R for 10 minutes. The control group was subjected to sham surgery only, and the
other groups were injected with saline solution (SS; 0.1 mL) or heparin (100
IU/kg) via the inferior cava vein 5 minutes before I and 5 minutes before R and
55 minutes after the R begins in I-R groups. In all animals, cardiac samples were
stained with hematoxylin and eosin for optical microscopy analysis, and other
sample was processed for lipid peroxidation determination. In I-R groups, both
heparin and IPC showed significant protection compared to the SS group;
conversely, in animals subjected only to I, no protection was observed. Moreover,
when heparin was associated with IPC, I-R protection was compromised and the
ischemic injury increased. Data showed that IPC and heparin attenuated cardiac
dysfunction caused by intestinal I and I-R, but when used in association did not
show beneficial effects.
PMID- 25131054
TI - Ex situ regeneration of liver remnants hypothermically preserved for 24 hours.
AB - INTRODUCTION: After partial hepatectomy (PH), the liver remnant (LR) shows a
regenerative response, always keeping a percent relationship with the host. This
process has been well described in the literature, but several aspects still need
to be understood. There are no studies on hepatic LR regeneration during
hypothermic preservation. Thus, the objective of the present study was to analyze
LR regeneration after PH under conditions of hypothermal preservation. MATERIALS
AND METHODS: Twenty adult Wistar rats were divided into 4 experimental groups:
PHS (70% PH); PHP (70% PH of an organ perfused and preserved for 24 hours); PWL
(perfused whole liver preserved for 24 hours); and NPWL (nonperfused whole
liver). The liver was perfused with 250 mL Celsior solution with a catheter
connected to a 1.30-cm-high liquid column. Hepatic tissue samples were submitted
to immunohistochemical analysis for the evaluation of protein Ki67 expression,
related to the mechanism of cell proliferation, to analysis of micro-RNA
expression (miR-21 and miR-16) by real-time polymerase chain reaction, and to
analysis of mitochondrial function. Nonparametric statistical analysis was used
(P < .05). RESULTS: Ki67 analysis revealed that the PHP group showed 17.41% cell
proliferation in LR (P < .01) compared to PHS (42.22%), PWL (11.43%), and NPWL
(11.98%). miR-16 expression (proapoptotic) was found to be higher in the NPWL
group compared to all others (PHS, PHP, and PWL), with a statistically
significant difference between the NPWL group and the PHS and PHP groups.
CONCLUSION: The animals submitted to PHS and PHP presenting greater Ki67
expression showed low miR-16 expression, indicating a low apoptotic index. In
summary, the LR showed ex situ regeneration even under hypothermal conditions.
There are no similar data in the literature surveyed.
PMID- 25131055
TI - Ischemic preconditioning and atenolol on lung injury after intestinal ischemia
and reperfusion in rats.
AB - The aim of this study was evaluate the beta blocker atenolol (AT) and ischemic
preconditioning (IPC) strategies for tissue protection against systemic effects
of intestinal ischemia (I) and reperfusion (R) injury. Forty-two rats were
pretreated with AT (1.5 mg . kg(-1)), 0.9% saline solution (SS; 0.1 mL), or IPC
and then subjected to prolonged occlusion of the superior mesenteric artery for
60 minutes leading to I followed or not by 120 minutes of R, according to the
group. For IPC, 5 minutes of I prior to 10 minutes of R were established. After
this process of I or I-R, the right lung of each animal was adequately prepared
for staining with hematoxylin and eosin and subsequent histologic analysis for
quantification of inflammatory infiltrate was done. The left lung was frozen and
prepared for assessment of oxidative stress by the quantification of
thiobarbituric acid-reactivity substances (TBARS). Histologic analysis showed an
important inflammatory infiltrate in the I-R + SS (I-R + SS = 4.5), which was
significantly (P < .05) reduced by IPC (I-R + IPC = 3.0) or AT (I-R + AT = 3.0).
Likewise, the TBARS levels were decreased by both strategies (I-R + SS = 0.63; I
R + IPC = 0.23; I-R + AT = 0.38; P < .05). Our results showed that AT and IPC
attenuate pulmonary lesions caused by intestinal I and R process.
PMID- 25131056
TI - Effect of ischemic preconditioning and postconditioning on liver regeneration in
prepubertal rats.
AB - BACKGROUND: Liver regeneration has great importance for transplantation,
especially in children; however, it has not been studied sufficiently in
development animals. Ischemia-reperfusion injury is a problem, and strategies
such as ischemic preconditioning and postconditioning are not well defined
regarding regeneration. OBJECTIVE: This study sought to evaluate liver
regeneration with modulation by ischemic preconditioning and postconditioning in
prepubertal rats subjected to total ischemia and reperfusion. METHODS: Thirty
five 5-week-old female Wistar rats were divided into groups of 7 animals each:
control group (SHAM), 70% hepatectomy (HEP), total ischemia 30 minutes before
hepatectomy (IR), ischemic preconditioning 10/10 minutes before ischemia (PRE),
and two 30/30-second ischemic postconditioning cycles after ischemia and
hepatectomy (POS). All animals were subjected to 24-hour reperfusion. Aspartate
aminotransferase and alanine aminotransferase activity were measured to evaluate
liver damage, and histological analysis, proliferating cell nuclear antigen
(PCNA) and regenerated mass liver were used to evaluate liver regeneration.
Statistical analyses were performed using ANOVA and Kruskal-Wallis test. RESULTS:
Alanine aminotransferase and aspartate aminotransferase levels were significantly
lower in conditioned groups than in the IR group. Regarding mitotic index, IR >
control group and HEP (P < .05), PRE and POS were not significantly different
from IR, and POS > HEP (P < .05). PCNA analysis showed that IR > HEP (P < .01),
PRE < IR (P < .01), and no significant differences were observed between POS and
IR groups. No significant differences in regenerated mass liver were observed
between conditioned groups and HEP. CONCLUSIONS: Ischemic postconditioning
prevented ischemic injury, promoted greater liver regeneration, and should be
further investigated as an alternative better than ischemic preconditioning.
PMID- 25131057
TI - Effects of immunosuppressive drugs on gastrointestinal transit of rats: effects
of tacrolimus, cyclosporine, and prednisone.
AB - Triple immunosuppressive therapy after organ transplantation may cause several
gastrointestinal disturbances. It is difficult to identify which drug causes more
complications, requiring an appropriate animal model. The aim was to compare the
gastrointestinal transit in immunosuppressed rats under triple immunosuppressive
therapy. Male rats were immunosuppressed by gavage during 14 days with tacrolimus
(n = 10), cyclosporine (n = 12), and prednisone (n = 9). Animals received a
magnetic pellet before (control) and after treatment that was monitored at
predetermined intervals by AC biosusceptometry, a noninvasive and radiation-free
technique. The following parameters were measured: creatinine serum, mean time of
gastric emptying (MGET), mean time to reach cecum (MCAT), and mean transit time
through small bowel (MSBTT). The differences were analyzed by ANOVA (Tukey). Our
results showed that MGET of animals treated with prednisone, cyclosporine, and
tacrolimus were reduced compared with control subjects (P < .03, P < .009, and P
< .002, respectively). There was no difference in MCAT, whereas MSBTT was longer
for tacrolimus and prednisone compared with control subjects (P < .004 and P <
.004, respectively). Also, prednisone and tacrolimus presented a reduced MGET (P
< .05 and P < .01, respectively) compared with cyclosporine. Our data showed a
low serum creatinine level and no difference among groups regarding renal
function. In summary, cyclosporine has less effect on the gastrointestinal
transit; however, all of these drugs should be carefully prescribed to prevent
gastrointestinal symptoms and improve quality of life after transplantation.
PMID- 25131058
TI - Late biliary obstruction in Wistar rats after intermittent hepatic pedicle
clamping.
AB - INTRODUCTION: The temporary vascular occlusion of hepatic flow is one of the
essential procedures in hepatic surgery. AIM: Evaluate the late liver alterations
after intermittent pedicle hepatic clamping (IHPC) in Wistar rats. METHODS: Male
Wistar rats (n = 14) with average weight of 281.1 g, were anesthetized with
intraperitoneal ketamine 5%. The IHPC group (n = 7) was submitted to U-shaped
abdominal incision; the hepatic pedicle was isolated and submitted to IHPC
ischemia 4 times, 5 minutes each, followed by reperfusion 4 times, 5 minutes
each. The simulated operation group (n = 7) was subjected to anesthesia,
laparotomy, and manipulation of the hepatic pedicle. On day 35, after fasting for
12 hours, liver biopsies were collected and blood was tested for liver
aminotransferases (aspartate aminotransferase/alanine aminotransferase). RESULTS:
All the IHPC group animals had a dilated common bile duct and increased liver
enzymes (P < .05 by Mann-Whitney test). Ductular proliferation (100% of cases),
porta-porta septa (42.8%), formation of lumps (42.8%), foci of necrosis (14.2%),
and bile plugs (14, 2%) were observed only in the IHPC group. CONCLUSION: In
rats, IHPC caused morphologic features leading to biliary obstruction.
PMID- 25131059
TI - Effect of platelet-rich plasma therapy associated with exercise training in
musculoskeletal healing in rats.
AB - BACKGROUND: Muscle healing is a time-dependent process associated with an
increase in the total amount of local collagen fibers. Platelet-rich plasma
therapy (PRPT) associated with exercise may improve this healing process. The aim
of this study was to demonstrate the regenerative effect of PRPT in association
with exercise training on musculoskeletal healing. METHODS: Male Wistar rats were
submitted to an injury in the vastus lateralis muscle and randomly divided into 4
groups (n = 5/group): sedentary sham-operated (SSO); sedentary group submitted to
PRPT (SPR); swim-trained (SWT); and swim-trained group submitted to PRPT (SWP).
Serum lactate level was used to confirm the training protocol effectiveness to
increase aerobic fitness. The collagen fiber concentration was measured by the
polarization colors in picrosirius red-stained tissue sections. RESULTS: Lactate
levels decreased in both training groups (SWT and SWP; P < .05) after training
(SWT: from 6.2 +/- 0.44 to 4.7 +/- 0.22 mmol/L; SWP: from 5.5 +/- 0.99 to 4.0 +/-
0.78 mmol/L). There were less type 1 collagen fibers in SWP group compared with
other groups (SSO = 31.8 +/- 10.3, SSP = 32.3 +/- 13.5, SWT = 14.6 +/- 13.4, SWP
= 5.7 +/- 4.7, P < .05), while there were more type 3 collagen fibers on SWP (SSO
= 68.7 +/- 9.8, SSP = 71.2 +/- 12.2, SWT = 85.4 +/- 13.4, SWP = 94.4 +/- 4.6, P <
.05) in the injured region. CONCLUSION: Exercise in association with PRPT
enhances the skeletal muscle-healing process.
PMID- 25131060
TI - Regeneration of skin tissue promoted by mesenchymal stem cells seeded in
nanostructured membrane.
AB - BACKGROUND: The mesenchymal stem cell therapy has proven to be an effective
option in the treatment of skin injuries. The combination of these cells with
nanostructured membranes seems to be the future for tissues recovery. The aim of
this project was to use biomolecules of polysaccharides to be incorporated on
regenerated cellulose membranes and to prospect the improvement as bioactive
wound dressings with mesenchymal stem cells. METHODS: The biocomposites were
obtained after defibrillation with the use of never-dried bacterial cellulose to
form a pulp, and, after the films were regenerated, in the presence of gellan gum
with or without fluconazole. Membrane atomic force microscopy was performed for
comparison of their structures. RESULTS: Adipose-derived mesenchymal stem cells
were obtained from human adipose tissue liposuction in accordance with Zuk et al.
The flow cytometric analysis and induction tests for adipocytes and osteocytes
were performed. In vitro assays were performed on different membranes to evaluate
the ability of these cells to adhere at 2 hours and proliferate at 7 days; the
results were obtained by use of the MTT cell counting technique. In vivo testing
allowed us to observe cell migration and participation in wound-healing by
fluorescence labeling of the cells with BrdU. The bioactive curative, seeded with
cells, was tested in skin burned in a murine model. CONCLUSIONS: The bacterial
cellulose with gelan gum membrane incorporated with fluconazole presented the
best performance in adhesion and proliferation tests. The cells can be identified
in burned host tissue after occurrence of the wound.
PMID- 25131061
TI - Rhabdomyolysis as a clinical manifestation of association with ciprofibrate,
sirolimus, cyclosporine, and pegylated interferon-alpha in liver-transplanted
patients: a case report and literature review.
AB - BACKGROUND: Rhabdomyolysis is a syndrome characterized by impaired metabolic
integrity of myocytes, causing the release of intracellular constituents into the
circulation, and can be a serious side effect of drug intake. CASE REPORT: This
report describes a unique case of rabdomyolysis secondary in which ciprofibrate,
sirolimus, cyclosporine, and pegylated interferon-alpha in a liver transplant
patient was used. A 47-year-old male liver transplant recipient in 2009, who had
hepatitis C and incidental hepatocellular carcinoma, underwent immunosuppressive
therapy (cyclosporine and sirolimus). The patient is currently in treatment for
viral recurrence with pegylated interferon-alpha and ribavirin; he had a history
of hypertriglyceridemia treated with ciprofibrate. He had development of severe
and generalized myalgia and fever after the eighth application of pegylated
interferon-alpha and increasing doses of cyclosporine. Laboratorial tests showed
acute renal failure and significant increase in creatine kinase. Rhabdomyolysis
secondary to interaction of fibrate-cyclosporine-pegylated interferon-alpha was
postulated. CONCLUSIONS: Medical professionals should be aware of possible drug
interactions and should monitor patients receiving these drugs.
PMID- 25131062
TI - Endovascular management of massive hemobilia as a late complication of
percutaneous biliary drainage in a pediatric liver transplant recipient: a case
report.
AB - Development of biliary strictures after liver transplantation is not uncommon,
and minimally invasive procedures are the first-line treatment of choice in most
centers. Hemobilia is an infrequent, usually self-limited complication related to
the initial biliary access procedure. Massive hemobilia with severe hemodynamic
instability is a rare event, particularly as a delayed complication. The
difficulty of obtaining surgical access makes management of this condition highly
challenging. Endovascular embolization may represent an important treatment
option in this setting.
PMID- 25131063
TI - Hepatic artery thrombosis in live liver donor transplantation: how to solve--a
case report.
AB - The decrease in the number of cadaveric donors has proved a limiting factor in
the number of liver transplants, leading to the death of many patients on the
waiting list. The living donor liver transplantation is an option that allows, in
selected cases, increase the number of donors. One of the most serious
complications in liver transplantation is hepatic artery thrombosis, in the past
considered potentially fatal without urgent re-transplantation. A white male
patient, 48 years old, diagnosed with hepatocellular carcinoma in chronic liver
failure caused by hepatitis B virus, underwent living donor liver transplantation
(right lobe). Doppler echocardiography performed in the immediate postoperative
period did not identify arterial flow in the right branch, having been confirmed
thrombosis of the right hepatic artery in CT angiography. Urgent re-laparotomy
was performed, which consisted of thrombectomy and re-anastomosis of the hepatic
artery with segmental splenic artery allograft interposition. The patient started
anticoagulation and antiplatelet therapy with acetylsalicylic acid. Serial
evaluation with Doppler echocardiography showed hepatic artery patency. At
present, the patient is asymptomatic. One of the most devastating complications
in liver transplantation, and particularly in living liver donor, is thrombosis
of the hepatic artery; thus, early diagnosis and treatment is vital. The rapid
intervention for revascularization of the graft avoids irreversible ischemia of
the bile ducts and hepatic parenchyma, thus avoiding the need for re
transplantation.
PMID- 25131065
TI - What defines success in pancreas and islet transplantation-insulin independence
or prevention of hypoglycemia? A review.
AB - Pancreas transplantation is considered to be the treatment of choice for selected
uremic and diabetic patients, and insurance coverage is widely provided. In the
USA, islet transplantation is considered to be an experimental procedure that
awaits formal results of ongoing phase III trials to justify biologic licensure
and transition to standard of care. Pancreas and islet registry analyses focus on
different functional endpoints: insulin independence (pancreas transplants)
versus avoidance of hypoglycemia (islet transplants). Although the results of
islet transplants have significantly improved, the frequent use of multiple donor
organs, suboptimal islet yields, and difficulties in monitoring successful
engraftment or in diagnosing rejection remain major barriers that need to be
overcome. Although pancreas and islet transplantations are frequently considered
to be competing procedures, they are actually complementary treatment options for
patients with type 1 diabetes mellitus. Because the results of pancreas
transplants are superior to those for islet transplants, diabetic patients with a
low surgical risk should undergo a pancreas transplantation. Type 1 diabetics
with a high surgical risk (eg, serious comorbidities) should undergo an islet
transplantation. Only an integrated approach to pancreas and islet
transplantation, tailored to the need of the individual patient, will maximize
the benefit of a scarce resource. Both procedures, if successful, have in common
that they represent the only biologic treatment option to date for type 1
diabetic patients that prevents hypoglycemia long term.
PMID- 25131066
TI - Short and long-term outcomes of systemic drainage to IVC: a new technique for
pancreas transplantation.
AB - Ninety-eight percent of the whole pancreas does not serve the purpose of
pancreatic transplantation and it is a major cause of surgical complications. Up
to 30% of pancreas transplant recipients experience surgical complications and
require reoperation. Graft thrombosis and pancreatitis are the most common
complications of pancreas transplantation (PT). Thus, different surgical
techniques have been described to overcome the surgical hurdles and reduce
surgical complications. In this study, for the first time, we report short- and
long-term outcomes of PT with inferior vena cava (IVC) venous drainage. Forty
five PTs (22 simultaneous pancreas and kidney [SPK] transplantations and 23
pancreas after kidney [PAK] transplantations) were performed with this technique
in our center. Sixty-eight percent of the donors were imported from outside of
our area after they were declined by their local transplantation center. Patient
and graft survival rates were 100% at 1 year. No graft thrombosis or pancreatitis
occurred with this technique. Six patients (13.3%) required reoperation (3
bleeding, 2 anastomotic leak, and 1 small bowel perforation). No patient or graft
loss occurred due to surgical complications. We conclude that this technique
provides fast and easy dissection of the venous drainage of the PT without the
need of complete occlusion of venous outflow. Surgical complication rates were
lower with this technique compared with other reported techniques.
PMID- 25131067
TI - Simultaneous pancreas-kidney transplantation with duodeno-duodenal anastomosis.
AB - Simultaneous pancreas-kidney transplantation (SPKT) is now accepted as the method
of choice for patients with insulin-dependent diabetes mellitus (type I) who have
end-stage renal disease (ESRD). We believe that retroperitoneal positioning of
the donor pancreas with the formation of duodeno-duodenal anastomosis is the most
physiologically relevant. Starting in January 2008, the SPKT was chosen as the
treatment method of 32 patients with diabetes mellitus. In 15 cases comprising
group I (46.9%), the pancreas was placed intra-abdominally (including the
formation of the duodeno-jejunal anastomosis). In the remaining 17 patients
(53.1%) comprising group II, the pancreas was positioned retroperitoneally
(including the formation of the duodeno-duodenal anastomosis). We compared the
main parameters of the early postoperative period in these groups. There were no
substantial differences between the groups in the prevalence of immunological
(13.3% and 11.8%, P = .9), surgical (20% and 23.5%, P = .81), and infectious
complications (20% and 5.9%, P = .23). On discharge there were no significant
differences in the values of the following between the two groups, respectively:
serum creatinine values, 112.7 +/- 31.2 and 104.8 +/- 54.6 MUmol/L, P = .17;
glomerular filtration rate, 73.5 +/- 28.6 and 78.7 +/- 24.9 mL/min, P = .55;
alpha-amylase, 121.9 +/- 63.6 and 150.1 +/- 72.1 U/L, P = .27; pancreatic
amylase, 102 +/- 51.5 and 122.5 +/- 75.4 U/L, P = .6; lipase, 115.4 +/- 67.3 and
96 +/- 65.7 U/L, P = .5; S-peptide, 4.44 +/- 1.9 and 4.02 +/- 2.4 ng/mL, P = .47;
HbA1c, 5.45 +/- 0.8% and 5.56 +/- 1.12%, P = .9; and intact insulin, 12.2 +/- 5.4
and 12.9 +/- 8.8 mcIU/mL, P = .95). SPKT remains the best method of medical and
social rehabilitation for patients who have diabetes mellitus (type-I) with ESRD.
Compared to the classic method, we have seen no significant deviations in either
of the following: the qualitative features marking the restoration of function of
the two transplanted organs and/or the quality of compensation of carbohydrate
metabolism, incidence of rejection, and graft loss. At the same time,
retroperitoneal positioning of the pancreas exhibited lower repeat surgery rates.
PMID- 25131068
TI - Portal versus systemic venous drainage of the pancreatic graft: the effect on
glucose metabolism in pancreas and kidney transplant recipients.
AB - Two different methods of graft venous drainage are used in pancreas
transplantation: portal (PVD) and systemic (SVD). PVD is considered to be more
physiologic due to its similarity to venous outflow of the native pancreas. The
aim of our study was to compare glucose metabolism in Type 1 diabetic recipients
of kidney and pancreatic grafts with PVD versus SVD by intravenous glucose
tolerance test (IVGTT). We examined 28 insulin-independent patients after
simultaneous pancreas and kidney transplantation: 14 recipients with PVD of the
pancreatic graft and 14 with SVD after a mean post-transplant period of 1 year.
All recipients had stable good function of the kidney graft. Fasting glycemia,
insulin levels, glycosylated hemoglobin (HbA1c), and standard IVGTT with
coefficient of glucose assimilation (KG) calculation were assessed. Insulin
sensitivity and production were evaluated using the homeostasis model assessment
(homeostasis model assessment of insulin resistance [HOMA-IR], homeostasis model
assessment of B-cell function [HOMA-B]). Total C-peptide and insulin secretions
were calculated as areas under the curves (AUCs) from the serum levels during the
IVGTT. PVD and SVD groups did not differ in age, body mass index (BMI) and
duration of post-transplantation period (P >= .05). We did not find any
significant difference in fasting glycemia, HbA1c, KG, HOMA-IR, parameters of C
peptide level, fasting insulin level, and response during IVGTT. HOMA-B and AUC
of insulin level were higher in the SVD group (45.1 +/- 35.1 versus 19.8 +/-
15.5, P =.03 and 1075 +/- 612 versus 1799 +/- 954 mIU/L/60 minutes, P < .03,
respectively). In the PVD group, 1 patient had an abnormal response to the
glucose stimulus, 8 patients had an impaired glucose tolerance, and 5 patients
had a normal glucose tolerance. In the SVD group, an abnormal response was
present in none, impaired glucose tolerance in 4, and normal glucose tolerance in
10 recipients. Athough this was not a prospectively randomized trial, we conclude
that the change of surgical technique from SVD to PVD did not lead to any
substantial change in terms of glucose tolerance.
PMID- 25131069
TI - Evaluation of insulin independence using 11C-methionine positron emission
tomography after living-donor and brain-dead donor pancreas transplantation.
AB - We recently reported that (11)C-methionine positron-emission tomography (PET) is
clinically useful for the evaluation of the pancreatic function of the living
donor. The objective of this study was to evaluate the postoperative insulin
independence in 10 living donor (LD) and 10 brain-dead donor (BD) pancreas
transplantations for 20 patients with type I diabetes mellitus by using (11)C
methionine PET. After 6 months, PET/computed tomography was performed 30 minutes
after (11)C-methionine (370-740 MBq) injection. The uptake in the pancreas was
expressed as the standardized uptake value (SUV). Patient survival rates were
100% at 5 years for LD transplantations and at 2 years for BD transplantations.
Insulin independence was 60% for LD transplantations at 5 years and 75% for BD
transplantations at 2 years. There were no major surgical complications such as
vascular thrombosis, intra-abdominal abscess, and graft pancreatitis. The SUVs
for LD and BD pancreas transplantations with insulin independence were 7.2 +/-
1.8 and 10.4 +/- 2.3, respectively. The SUVs for LD pancreas transplantations
with insulin dependence and BD pancreas transplantations with graft failure were
3.6 +/- 1.1 and 2.9 +/- 1.0, respectively. At 5 years after transplantation, for
the LD transplants, the insulin-independent rate was 100% for the graft
recipients with an SUV higher than 5, and the median insulin independence
duration of the graft recipients with an SUV less than 5 was 7 months (P < .01).
The (11)C-methionine PET may be a potent modality to predict long-term insulin
independence and the avoidance of pancreas graft failure.
PMID- 25131070
TI - A novel screening test for detecting graft thrombosis after pancreatic
transplantation using contrast-enhanced ultrasonography with sonazoid.
AB - Pancreatic graft thrombosis is the primary cause of nonimmunologic graft loss,
with an incidence ranging from 5% to 15%. Therefore, developing a screening test
to detect graft thrombosis after pancreatic transplantation is important. We
created a screening test to assess graft thrombosis after pancreatic
transplantation using contrast-enhanced ultrasonography (CEUS) with Sonazoid in
addition to Doppler ultrasonography. A total of seven patients were examined
using CEUS after undergoing pancreatic transplantation. All patients were
observed to have a clear blood flow from the horizontal region to the peripheral
region of the splenic vein in the pancreatic graft, and only one of the seven
patients exhibited a blood flow in the horizontal portion of the splenic vein on
Doppler ultrasonography performed immediately after pancreatic transplantation.
Results from CEUS with Sonazoid showed the blood flow in the splenic vein and
parenchyma of the pancreatic graft in detail, despite the slow and lateral blood
flow in the splenic vein of the pancreatic graft immediately after
transplantation.
PMID- 25131071
TI - Long-term outcomes of pancreas after kidney transplantation in small centers: is
it justified?
AB - BACKGROUND: Currently, the long-term advantages of having a pancreas
transplantation (PT) are debated, particularly in patients receiving pancreas
after kidney (PAK) allografts. The United Network for Organ Sharing (UNOS)
requires that a transplant center perform a minimum number of PT per year to
remain an active PT center. The long-term outcomes and challenges of PAK in small
pancreas transplant centers are not well studied. METHODS: In this retrospective
analysis, we report short- and long-term outcomes in a small center performing 2
9 PT annually. RESULTS: Forty-eight PT (25 simultaneous pancreas and kidney
transplantation [SPK], 23 PAK) were performed in our center. Donor and recipient
demographics were similar in both groups. All suitable local donors were used for
SPK. All organs for PAK transplantation were imported from other UNOS regions.
Mean follow-up was 61 +/- 46 and 74 +/- 46 months for SPK and PAK, respectively.
Patient and graft survival rates were similar in SPK and PAK groups and better
than the reported national average. Four patients (11%) died (1 due to trauma, 1
brain lymphoma, 1 ruptured aneurysm; and 1 unknown cause). Two patients (4%; 1
SPK, 1 PAK) lost their grafts because of thrombosis on postoperative days 3 and 5
in 2002. No graft thrombosis occurred since 2002. Seven patients (15%) required
reoperation (4 for bleeding, 2 anastomotic leaks, 1 small bowel perforation). Two
patients (4%) developed post-transplantation lymphoproliferative disease. Five
patients (11%) experienced cytomegalovirus antigenemia which responded well to
antiviral therapy. CONCLUSIONS: Compared with outcomes for diabetic patients on
dialysis, current SPK and PAK short- and long-term results are favorable even in
a small PT center. Therefore, unless there is a contraindication, PT should be
offered to all type 1 diabetic patients with end-stage renal disease at the time
of kidney transplantation or afterward.
PMID- 25131072
TI - Similar results with solitary pancreas transplantation compared with simultaneous
pancreas-kidney transplantation in the new millennium.
AB - INTRODUCTION: The purpose of this study was to analyze our single-center outcomes
according to pancreas transplant (PT) category in the new millennium by using
standardized management protocols. PATIENTS AND METHODS: We retrospectively
studied 202 consecutive PTs (179 with portal-enteric drainage) in 192 patients;
all received either rabbit antithymocyte globulin or alemtuzumab induction in
combination with tacrolimus, mycophenolate mofetil, and tapered corticosteroids
or early steroid withdrawal. Unlike simultaneous pancreas/kidney (SPK)
transplant, solitary PT (SPT) recipients were managed with routine perioperative
anticoagulation and surveillance pancreas biopsies. RESULTS: From November 2001
to March 2013, we performed 162 SPK transplants, 35 pancreas after kidney
transplants, and 5 pancreas-alone transplants (40 SPTs). Demographic
characteristics were mostly comparable; however, the SPT group had younger
donors, shorter waiting time, fewer HLA mismatches, and fewer African-American
recipients but more retransplants (all, P < .05). With a mean follow-up of 5.5
versus 7.5 years, overall patient (86.4% SPK vs 86.8% SPT), kidney graft (74% SPK
vs 80% SPT), and pancreas graft (both 65%) survival rates were comparable.
Although mortality rates were similar, mortality patterns differed because no SPT
recipients died early, whereas the 1-, 3-, and 5-year mortality rates after SPK
transplant were 4%, 9% and 12%, respectively (P < .05). The most common causes of
pancreas graft loss were death with functioning grafts in SPK recipients and
acute/chronic rejection in SPT recipients. Rates of early thrombosis were 8.6% in
SPK patients and 5% in SPT patients. Cumulative clinical acute rejection rates
were similar between groups (SPK 29% vs SPT 27.5%; P = NS). CONCLUSIONS: In the
setting of depleting antibody induction and tacrolimus-based therapy, HLA
matching, careful donor and recipient selection, portal-enteric drainage,
selective perioperative anticoagulation, and surveillance SPT biopsy monitoring,
similar medium-term outcomes can be achieved in SPK transplants and SPTs in the
new millennium.
PMID- 25131073
TI - 5-year results of a prospective, randomized, single-center study of alemtuzumab
compared with rabbit antithymocyte globulin induction in simultaneous kidney
pancreas transplantation.
AB - INTRODUCTION: The study purpose was to analyze 5-year outcomes in a prospective,
randomized trial of alemtuzumab (ALEM) versus rabbit antithymocyte globulin
(rATG) induction in simultaneous kidney-pancreas transplantation (SKPT). PATIENTS
AND METHODS: From February 2005 through October 2008, a total of 46 SKPTs (45
portal-enteric drainage) were prospectively randomized to receive either single
dose ALEM (30 mg intraoperatively) or multiple-dose rATG antibody induction
(starting intraoperatively, minimum of 3 doses administered) with
tacrolimus/mycophenolate and/or steroids. RESULTS: Of 222 kidney transplant
patients enrolled in the study, 46 received SKPTs; 28 (61%) received ALEM and 18
(39%) received rATG induction. Follow-up ranged from 54 to 98 months (mean, 69
months). There were no significant differences between the 2 groups in 5-year
patient (82% ALEM vs 89% rATG), kidney graft (79% ALEM vs 72% rATG), or pancreas
graft (64% ALEM vs 56% rATG) survival rates. Death-censored kidney (90% ALEM vs
75% rATG) and pancreas (71% ALEM vs 56% rATG) graft survival rates were likewise
comparable (both, P = NS). Acute rejection (21% ALEM vs 44% rATG; P = .11) and
major infection (39% ALEM vs 67% rATG; P = .13) rates were slightly lower in the
ALEM group; cytomegalovirus infections were significantly lower (0% ALEM vs 17%
rATG; P = .05). The incidence of late acute rejection was low in both groups.
There were no differences in early pancreas thromboses (3.6% ALEM vs 11% rATG),
postoperative bleeding (11% ALEM vs 0% rATG), other surgical complications, or
readmissions between groups. In patients with functioning grafts, 5-year mean
serum creatinine (1.4 ALEM vs 1.6 mg/dL rATG), calculated abbreviated
Modification of Diet in Renal Disease glomerular filtration rate (55 ALEM vs 52
mL/min/1.73 m(2) rATG), glycosylated hemoglobin (both 5.4%), and C-peptide (2.2
ALEM vs 2.3 ng/mL rATG) levels were similar. CONCLUSIONS: Single-dose ALEM and
multiple dose rATG induction provided similar medium-term patient, kidney, and
pancreas graft function and survival rates. ALEM induction may be associated with
less acute rejection and major infection over the long term.
PMID- 25131074
TI - Excellent outcomes can be achieved in young pancreas transplant alone recipients
by addition of sirolimus to maintenance immunosuppression regimen.
AB - BACKGROUND: Pancreas transplant alone (PTA) has evolved into a viable treatment
option for nonuremic patients with labile diabetes mellitus. Historically, PTA
outcomes were inferior to simultaneous pancreas-kidney transplant outcomes,
because of the higher rate of graft loss due to rejection in PTA recipients. But
with advances in immunosuppression, PTA outcomes have improved significantly-
except in young PTA recipients. The more potent immune system in young recipients
appears to play a key role. In this study, our objective was to investigate
outcomes of PTA, by recipient age, with the use of different immunosuppressive
maintenance regimens. METHODS: Using information from the International Pancreas
Transplant Registry and from the United Network for Organ Sharing, we analyzed
outcomes of 393 technically successful enteric-drained transplants in the PTA
category that were performed from January 2003 through December 2012. All PTA
recipients underwent induction immunosuppression with thymoglobulin and pulse
steroids and were then maintained on long-term low-dose prednisone. Excluded from
our study group were patients who experienced surgical graft loss. We divided the
393 recipients into 2 age groups: <42 years (187 patients) versus >=42 years (206
patients). For both the younger group and the older group, we compared 2
maintenance immunosuppressive regimens: (1) tacrolimus (Tac) and mycophenolate
mofetil (MMF) versus (2) Tac/MMF and sirolimus (Srl). We refer to
immunosuppression with Tac and MMF as the non-Srl regimen. RESULTS: The overall 3
year graft survival rate, across both age groups, was significantly better with
the Srl regimen (P = .03). Regardless of the immunosuppressive regimen used,
outcomes were significantly better in the older group than in the younger group
(P = .05). In the older group, with both regimens, outcomes were similar (P =
.55). But in the younger group, outcomes with the Srl regimen were significantly
better (P = .009) than with the non-Srl regimen and, in fact, were similar to
outcomes in the older group. CONCLUSIONS: Our study shows that adding Srl to the
standard maintenance immunosuppressive regimen of Tac and MMF provides the best
outcomes in young PTA recipients, the most immunologically robust and therefore
the most immunologically challenging age group. To achieve excellent outcomes,
more potent immunosuppression is required in this cohort. We think that PTA
should be offered to young patients with labile diabetes before secondary
complications develop.
PMID- 25131075
TI - Declining numbers of pancreas transplantations but significant improvements in
outcome.
AB - In the United States, over the past 8 years, the number of pancreas
transplantations has steadily declined. This decline comes as a surprise, because
patient and graft outcomes have substantially improved during the same period of
time. Patient survival rates at 1 year in all 3 recipient categories are >96%;
graft survival rates are 82%-89%. Changes in immunosuppressive therapy have had a
positive impact on outcome, as have better pancreas donor and recipient selection
criteria and refined post-transplantation patient care. Although different
factors may have contributed to the declining pancreas transplantation numbers, a
more effective process of publicly promoting and widely communicating the
improved results of pancreas transplantation is warranted.
PMID- 25131076
TI - High urine amylase level and the risk of enteric conversion in solitary pancreas
transplant recipients.
AB - INTRODUCTION: Compared with enteric drainage, bladder-drained solitary pancreas
transplants can be monitored for rejection by measuring urine amylase levels.
However, bladder drainage is associated with a higher risk of infection and
metabolic complications, necessitating enteric conversion in about one third of
patients. We hypothesized that hypersecreting pancreata with high urine amylase
levels have a higher propensity for enteric conversion from an antecedent
elevated enzymatic effect on the urinary tract and increased fluid losses.
PATIENTS AND METHODS: We analyzed the risk for enteric conversion in 312 bladder
drained solitary pancreas transplant recipients. Urine amylase levels at 30 days
were used to identify those at risk for enteric conversion. Time-to-event
analysis was used to evaluate the risk of enteric conversion at 10 years,
adjusting for urine amylase level and other confounding factors. Confounding risk
factors statistically related to enteric conversion were incorporated into the
multivariable analysis by using Cox proportional hazards regression at 3 years'
posttransplant. RESULTS: During the median follow-up of 184.6 months, 31% of
recipients underwent duct conversion. A majority of recipients (84.5%) who
required duct conversion were primary transplants. The 30-day median urine
amylase level was 1749 IU/h (quartile 1, <777 IU/h; quartile 3, >=3272 IU/h).
Using receiver operating characteristic analysis, it was determined that urine
amylase levels >3272 IU/h had the greatest specificity for predicting risk of
enteric conversion. In the multivariate analysis, high urine amylase levels
increased the risk of enteric conversion only in repeated pancreas transplants.
CONCLUSIONS: Primary transplants are more likely to undergo enteric conversion
than retransplants. High urine amylase levels increase the risk of enteric
conversion in retransplants only, and therefore this enzyme alone cannot serve as
the sole predictor for conversion in primary transplants. Other factors, such as
fluid and bicarbonate losses, increased bladder pressure, and a pre-existing
lower urinary tract pathologic condition may be also responsible for the
development of complications; these factors warrant additional study.
PMID- 25131077
TI - The influence of collagen III expression on the efficiency of cell isolation with
the use of collagenase H.
AB - OBJECTIVE: We previously demonstrated that collagenase H (ColH) plays a crucial
role in rat islet isolation, whereas collagenase G (ColG) plays only a supporting
role. We also showed that collagen III appears to be one of the key targets of
ColH based on a mass spectrometry analysis. In the present study, we investigated
whether our novel findings in an islet isolation model are universally applicable
for other types of cell isolation, such as a hepatocyte isolation, with the use
of enzyme blends of recombinant collagenases. METHODS: As the first step, the
expression of one of the main matrix components, collagen III, on rat pancreatic
and hepatic tissues was assessed with the use of immunohistochemical staining.
ColG and ColH were expressed in recombinant E. coli carrying expression plasmids
for each collagenase. Then the efficiency of the collagenase subtype on rat
hepatocyte isolation was evaluated in terms of cell yield with the use of
thermolysin combined with either ColG or ColH (n = 3, respectively). RESULTS: The
expression of collagen III on rat hepatic tissues was dramatically lower than
that of rat pancreatic tissues. In the rat hepatocyte isolation, a substantial
amount of hepatocytes (0.81 +/- 0.11 * 10(6)) were obtained in the ColG group,
whereas almost no hepatocytes were retrieved in the ColH group, indicating that
the influence of the collagenase subtypes in rat hepatocyte isolation are
completely opposite to that observed in rat islet isolation. CONCLUSIONS:
Considering that the expression of collagen III on hepatic tissues was relatively
low and that almost no hepatocytes were retrieved when ColH and thermolysin were
used, the present study supports our novel finding that collagen III appears to
be one of the key targets of ColH in hepatocyte isolation. Therefore, the
semiquantification of collagen III on the target tissues not only may positively
contribute to efficient islet isolation, but also may affect other types of cell
isolation by optimizing the ColH amount.
PMID- 25131078
TI - Pretreatment of donor pigs with a diet rich in soybean oil increases the yield of
isolated islets.
AB - INTRODUCTION: The pig is considered the donor species of choice for islet
xenotransplantation. However, isolation of porcine islets is difficult,
particularly from young pigs. Early life exposure to a high-fat diet (HFD)
reportedly encourages islet beta-cell expansion in neonatal rodents and improves
islet viability in culture from pretreated weanling pigs. In this study, we
examined the influence of young donor pretreatment with a soybean oil-enriched
HFD on porcine islet mass and yield after islet isolation. MATERIALS AND METHODS:
Postweaning and between days 70 and 250, pigs were fed either a standard diet
(control group; n = 5) or an HFD (experimental group; n = 6). Biochemical blood
parameters and acute C-peptide response to intravenous glucose were monitored
before pancreas procurement. The study was blinded to objectively evaluate the
influence of treated diet. After procurement, pancreas biopsy samples were taken
from control and pretreated donor pigs to assess islet number by using a
dithizone scoring method and histologic islet area fraction determination.
Control and HFD donor pig islets were isolated by using our standard isolation
protocol to determine islet yield. Islet isolation characteristics and islet
quality were assessed in both groups, and the results were compared. RESULTS:
There were no significant differences in the donor characteristics (age, body
weight, glucose disposal rate, acute C-peptide response to intravenous glucose,
cholesterol, and aspartate aminotransferase) except fasting blood glucose level
between the control and treatment groups (84 +/- 6 vs 99 +/- 12 mg/dL; P =
.0317). The stimulated insulin and C-peptide levels between groups were similar.
However, the dithizone score was slightly higher in the treatment group compared
with the control group (95.4 +/- 38.5 vs 62.6 +/- 23.9; P = .1208). Digestion
time, digested pancreas weight, pellet volume, and the fragility index were
similar in both groups. However, the average islet count (islet equivalent
number/g pancreas) at the digest level was significantly higher in the HFD group
than in the control group (1578 +/- 994 vs 738 +/- 202; P = .0344). The
functional viability of 2- and 7 day-cultured islets, as assessed by using oxygen
consumption rate corrected for DNA, was similar in both groups. CONCLUSIONS:
Pretreatment of pigs with HFD enriched with soybean oil could potentially be used
to improve the islet mass in donor pigs. Further studies are needed to confirm
and optimize the use of HFD for the purpose of increasing islet yield from young
donor pigs.
PMID- 25131079
TI - Effects of all-trans retinoid acid and exendin-4 on islet transplantation in NOD
mice.
AB - Type 1 diabetes usually develops due to autoimmune destruction of beta-cells in
the pancreas. It has been shown that all-trans retinoid acid (ATRA), a potent
derivative of vitamin A, hinders the development of autoimmune diabetes by
inducing immune tolerance status. In addition, exendin-4, a glucagon-like peptide
1 receptor agonist, stimulates growth and differentiation of beta-cells and
exerts anti-apoptotic effect on beta-cells. Thus, we hypothesized that the ATRA
and exendin-4 therapy may improve the outcome of islet transplantation in non
obese diabetic (NOD) mice. After the onset of diabetes, each NOD mouse was
transplanted with 300 or 600 islets isolated from NOD/severe combined
immunodeficient (SCID) mice with or without treatment of ATRA (0.5 mg
intraperitoneally every other day) and/or exendin-4 (3 MUg/kg subcutaneously
twice daily) for 6 weeks. After 300 or 600 NOD/SCID islet transplantation without
any other treatment, all NOD recipients remained diabetic. However, the lowest
blood glucose level in mice transplanted with 600 but not 300 islets was
significantly lower than those without islet transplantation (P < .05), although
their survival time was comparable. Among recipients treated with ATRA, exendin
4, ATRA and exendin-4, and without treatment, their lowest blood glucose levels
and survival time were not different. However, one recipient treated with ATRA
survived for 223 days with intermittent hyperglycemia and the other who was
treated with ATRA and exendin-4 achieved normoglycemia. In conclusion, islet
transplantation lowered blood glucose levels in diabetic NOD mice. With a few
exceptions, treatment with ATRA and exendin-4 alone or in combination in islet
recipients could not reverse diabetes or prolong survival.
PMID- 25131080
TI - Islet preparation purity is overestimated, and less pure fractions have lower
post-culture viability before clinical allotransplantation.
AB - BACKGROUND: Replacement of beta-cells with the use of isolated islet
allotransplantation (IT) is an emerging therapy for type 1 diabetics with
hypoglycemia unawareness. The current standard protocol calls for a 36-72-hour
culture period before IT. We examined 13 clinical islet preparations with >=2
purity fractions to determine the effect of culture on viability. METHODS: After
standard islet isolation and purification, pure islet fractions were placed at 37
degrees C with 5% CO2 for 12-24 hours and subsequently moved to 22 degrees C,
whereas less pure fractions were cultured at 22 degrees C for the entire
duration. Culture density was targeted at a range of 100-200 islet equivalents
(IEQ)/cm(2) adjusted for purity. Islets were assessed for purity (dithizone
staining), quantity (pellet volume and DNA), and viability (oxygen consumption
rate normalized to DNA content [OCR/DNA] and membrane integrity). RESULTS:
Results indicated that purity was overestimated, especially in less pure
fractions. This was evidenced by significantly larger observed pellet sizes than
expected and tissue amount as quantified with the use of a dsDNA assay when
available. Less pure fractions showed significantly lower OCR/DNA and membrane
integrity compared with pure. The difference in viability between the 2 purity
fractions may be due to a variety of reasons, including hypoxia, nutrient
deficiency, toxic metabolite accumulation, and/or proteolytic enzymes released by
acinar tissue impurities that are not neutralized by human serum albumin in the
culture media. CONCLUSIONS: Current clinical islet culture protocols should be
examined further, especially for less pure fractions, to ensure the maintenance
of viability before transplantation. Even though relatively small, the difference
in viability is important because the amount of dead or dying tissue introduced
into recipients may be dramatically increased, especially with less pure
preparations.
PMID- 25131081
TI - Assessment of human islet grafts in frozen sections of CD-1 athymic nu/nu mouse
liver for molecular analysis.
AB - BACKGROUND: Post-transplantation islet graft monitoring is hampered by a lack of
efficient methods to locate and analyze islets in situ. We evaluated histologic
methods to rapidly locate islets within the liver parenchyma post
transplantation, using several staining strategies, prior to analysis using laser
capture microdissection. METHODS: Human islets were isolated (n = 8) from brain
dead, multiorgan donor pancreases at the McGill University Health Centre Islet
Transplant Laboratory. Mean yield was 247,609 +/- 195,272 IE and 3172 +/- 1645
IE/g (purity and viability, respectively, 84.5 +/- 8.6% and 95 +/- 5% average;
mean +/- SD). Diabetic athymic CD-1 nu/nu mice (streptozotocin intraperitoneal
injection, 200 mg/kg) were maintained with sustained release insulin pellets
until a suitable islet preparation was available for transplant. Intraportal
islet transplantation of 2000 IE/mouse was performed via the ileocecal vein, as
previously described. Frozen sections of liver containing human islets were
prepared from specimens collected on days 0, 4, and 30 post-transplant. Every
twentieth slide from serial sectioned liver was stained using a rapid protocol to
determine if islets were present. Sections were fixed and stained for 5 minutes
with either an anti-human insulin fluorescein isothiocyanate (FITC)-conjugated
primary antibody (Ins-FITC), Newport Green (NG), or diphenylthiocarbazone
(dithizone, DZ). RESULTS: Islets were readily localized using each technique,
mostly toward the liver periphery. However, DZ had a faint appearance in 10-MUm
thick sections and was best utilized to locate sections containing islets during
sectioning. CONCLUSION: Ins-FITC, NG, and DZ are all good candidates for a rapid
islet staining protocol to evaluate human islet grafts in situ, with DZ being
best for sectioning and Ins-FITC and NG being equal in locating islets during
processing for laser capture microdissection.
PMID- 25131082
TI - Metabolic profile of pancreatic acinar and islet tissue in culture.
AB - BACKGROUND: The amount and condition of exocrine impurities may affect the
quality of islet preparations, especially during culture. In this study, the
objective was to determine the oxygen demand and viability of islet and acinar
tissue post-isolation and whether they change disproportionately while in
culture. METHOD: We compared the oxygen consumption rate (OCR) normalized to DNA
(OCR/DNA, a measure of fractional viability in units of nmol/min/mg DNA), and the
percent change in OCR and DNA recoveries between adult porcine islet and acinar
tissue from the same preparation (paired) over 6-9 days of standard culture.
Paired comparisons were done to quantify differences in OCR/DNA between islet and
acinar tissue from the same preparation, at specified time points during culture.
RESULTS: The mean (+/-SE) OCR/DNA was 74.0 +/- 11.7 units higher for acinar (vs
islet) tissue on the day of isolation (n = 16, P < .0001), but 25.7 +/- 9.4 units
lower after 1 day (n = 8, P = .03), 56.6 +/- 11.5 units lower after 2 days (n =
12, P = .0004), and 65.9 +/- 28.7 units lower after 8 days (n = 4, P = .2) in
culture. DNA and OCR recoveries decreased at different rates for acinar versus
islet tissue over 6-9 days in culture (n = 6). DNA recovery decreased to 24 +/-
7% for acinar and 75 +/- 8% for islets (P = .002). Similarly, OCR recovery
decreased to 16 +/- 3% for acinar and remained virtually constant for islets (P =
.005). CONCLUSION: Differences in the metabolic profile of acinar and islet
tissue should be considered when culturing impure islet preparations. OCR-based
measurements may help optimize pre-islet transplantation culture protocols.
PMID- 25131083
TI - Effect of mesenchymal stem cells on the vascularization of the artificial site
for islet transplantation in rats.
AB - An adequate vascularization of the artificially created cavity is crucial for
subsequent transplantation of isolated pancreatic islets. In a reported study,
dynamic contrast-enhanced magnetic resonance imaging was used to assess the
effect of mesenchymal stem cells on neoangiogenesis within connective tissue
surrounding an implantable biocompatible device. The signal increase detected
after injection of magnetic resonance contrast agent in each target region was
considered to be an effect of contrast agent, which was related to the blood
supply. To minimize the influence of variability in contrast agent application,
all outcomes measured in the implanted devices were normalized to the signal
intensity of kidney tissue. When supported by mesenchymal stem cells, the mean
signal increase intra-abdominally was 42%, 41%, and 64% and within subcutaneously
implanted devices was 23%, 54%, and 52% of that measured in kidney.
PMID- 25131085
TI - Donor height in combination with islet donor score improves pancreas donor
selection for pancreatic islet isolation and transplantation.
AB - To maximize the islet isolation yield for successful islet transplantation, the
key task has been to identify an ideal pancreas donor. Since implementation of
the islet donor score in donor selection, we have consistently obtained higher
islet yields and transplantation rates. In this study, we tested whether
assessing donor height as an independent variable in combination with the donor
score could improve the pancreas donor selection. Donor and islet isolation
information (n = 22) were collected and studied between 2011 and 2012. Pearson
correlation analysis was used in statistical analysis. Donor height as an
independent variable was significantly correlated to the weight of the pancreas,
pre-Islet Equivalents (pre-IEQ), post-IEQ, and IDS (P < .05). When donor with
height of 179 cm +/- 3 was selected in combination with IDS > 80, the clinical
islet transplantation rate reached 80%.
PMID- 25131084
TI - Improved coating of pancreatic islets with regulatory T cells to create local
immunosuppression by using the biotin-polyethylene glycol-succinimidyl valeric
acid ester molecule.
AB - BACKGROUND: We showed that T regulatory (Treg) cells can be attached to the
surface of pancreatic islets providing local immunoprotection. Further
optimization of the method can improve coating efficiency, which may prolong
graft survival. In this study, we compared the effectiveness of two different
molecules used for binding of the Tregs to the surface of pancreatic islets. Our
aim was to increase the number of Treg cells attached to islets without
compromising islets viability and function. METHODS: The cell surface of human
Treg cells and pancreatic islets was modified using biotin-polyethylene glycol-N
hydroxylsuccinimide (biotin-PEG-NHS) or biotin-PEG-succinimidyl valeric acid
ester (biotin-PEG-SVA). Then, islets were incubated with streptavidin as
islet/Treg cells binding molecule. Treg cells were stained with CellTracker CM
DiL dye and visualized using a Laser Scanning Confocal Microscope. The number of
Treg cells attached per islets surface area was analyzed by Imaris software. The
effect of coating on islet functionality was determined using the glucose
stimulated insulin response (GSIR) assay. RESULTS: The coating procedure with
biotin-PEG-SVA allowed for attaching 40% more Treg cells per 1 MUm(2) of islet
surface. Although viability was comparable, function of the islets after coating
using the biotin-PEG-SVA molecule was better preserved than with NHS molecule.
GSIR was 62% higher for islets coated with biotin-PEG-SVA compared to biotin-PEG
NHS. CONCLUSION: Coating of islets with Treg cells using biotin-PEG-SVA improves
effectiveness with better preservation of the islet function. Improvement of the
method of coating pancreatic islets with Treg cells could further facilitate the
effectiveness of this novel immunoprotective approach and translation into
clinical settings.
PMID- 25131086
TI - Impact of hypothermic preservation on tissue yield and viability in pig
pancreata.
AB - INTRODUCTION: Chronic shortage of quality human cadaveric pancreata limits islet
transplantation. Porcine islet xenotransplantation is being explored to increase
the donor pool. For clinical-ready islets, centralized animal husbandry, Current
Good Manufacturing Practice-regulated processing facilities, and organ
transportation support are required. Amount of cold ischemia time (CIT) before
isolation significantly affects transplantation. The goal of this study was to
determine the maximum safe CIT of whole pancreata before islet isolation.
MATERIALS AND METHODS: Pancreata were rapidly removed from Yorkshire pigs (age,
14-22 days) and stored in modified University of Wisconsin solution or in
EuroCollins solution at 4( degrees )C. Pancreata were processed with <1 hour CIT
(control) or stored for 4 or 12 hours before isolation. Islet yield and percent
purity and viability were determined after 7 days of in vitro tissue culture and
maturation. Samples from nonprocessed pancreata were collected and snap-frozen in
liquid nitrogen at 0, 3, 6, 9, 12, 15, and 24 hours of preservation, then
analyzed for adenosine diphosphate/adenosine triphosphate ratio as a measure of
tissue energetics. RESULTS: Up to 12 hours in cold storage had no significant
impact on overall islet yield after 7 days of in vitro culture compared with
controls; islet yield at the end of the maturation process was 28,700 +/- 500
islet equivalents per pancreas (mean +/- SEM control yield, 30,300 +/- 900 islet
equivalents per pancreas); islet purity was 75 +/- 5% compared with 74 +/- 5% in
controls. Islet viability was significantly reduced at 12 hours compared with
controls (80 +/- 6% vs 96 +/- 5%; P < .05). The tissue adenosine
diphosphate/adenosine triphosphate ratio was maintained within the first 6 hours
(1.6 +/- 0.1 to 1.8 +/- 0.2; P = NS) but was markedly increased during the 24
hour study (3.3 +/- 0.1 at 24 hours), indicating a progressive loss of adenosine
triphosphate tissue stores. CONCLUSIONS: Young pig pancreata can be
hypothermically stored for up to 12 hours without affecting islet yield and
purity; however, islet viability is reduced. These data highlight the need for
uniform shipping parameters to standardize islet quality, ideally with CIT <6
hours.
PMID- 25131087
TI - Results of open and robot-assisted pancreatectomies with autologous islet
transplantations: treating chronic pancreatitis and preventing surgically induced
diabetes.
AB - For patients with chronic pancreatitis (CP), standard surgical procedures (eg,
partial or total resections, drainage procedures) are inadequate treatment
options, because they do not confer pain relief and they leave patients prone to
brittle diabetes and hypoglycemia. The combination of total pancreatectomy and
islet autotransplantation (TP-IAT), however, can create insulin-independent and
pain-free states. At our center, from August 2009 through August 2013, 61
patients with CP underwent either open or robot-assisted TP-IAT. The 30-day
mortality rate was 0%. The transplanted islet equivalents per body weight ranged
from 10,000 to 17,770. In all, 19% of the patients became insulin independent
(after a range of 1-24 months); 27% of patients required <10 units of insulin.
Moreover, at 12 months after surgery, 71% of the patients were pain free and no
longer required analgesics. Our metabolic outcomes could have been even better if
most patients had been referred at an earlier disease stage; instead, ~80% had
already undergone surgical procedures, and 91% had abnormal results on
preoperative continuous glucose monitoring tests. Only if patients with CP are
referred early for a TP-IAT-rather than being subjected to additional inadequate
endoscopic and surgical procedures-can insulin-independent and pain-free states
be accomplished in most.
PMID- 25131088
TI - Long-term outcomes of clinical transplantation of pancreatic islets with
uncontrolled donors after cardiac death: a multicenter experience in Japan.
AB - BACKGROUND: Pancreatic islet transplantation has emerged as an effective
treatment for type 1 diabetes mellitus, but its use is limited due to an
insufficient supply of cadaveric pancreata. In Japan, uncontrolled donors after
cardiac death (DCD) are not deemed to be suitable for whole-organ pancreatic
transplantation, and can provide a source of pancreas for islet transplantation.
However, the long-term outcomes and utility of uncontrolled DCD in the clinical
setting remain controversial. Here, we summarize the long-term outcomes of islet
transplantation employing uncontrolled DCD as reported to the Japan Islet
Transplantation Registry. METHODS: Sixty-four isolations and 34 transplantations
of pancreatic islets were conducted in 18 subjects with type 1 diabetes mellitus
under the cover of immunosuppression with basiliximab, sirolimus, and tacrolimus.
All donors were uncontrolled DCD at the time of harvesting. The mean follow-up
time was 76 months. RESULTS: Of the 18 recipients, 8, 4, and 6 recipients
received 1, 2, and 3 islet infusions, respectively. Overall graft survivals
(defined as a C-peptide level >=0.3 ng/mL) were 72.2%, 44.4%, and 22.2% at 1, 2,
and 5 years, respectively, whereas the corresponding graft survivals after
multiple infusions were 90.0%, 70.0%, and 30.0%, respectively. Three of these
recipients achieved insulin independence in 14, 79, and 215 days. HbA1c levels
and the requirement of exogenous insulin were improved before loss of graft
function. All recipients became free of severe hypoglycemia unawareness, however,
at least 5 of 14 patients who had graft failure experienced recurrence of severe
hypoglycemia after the loss of graft function. CONCLUSIONS: Islet transplantation
from DCD can relieve glucose instability and problems with hypoglycemia when the
graft is functioning. However, islets from uncontrolled DCD may be associated
with reduced long-term graft survival. Further improvements in the clinical
outcome by modification of islet isolation/transplantation protocols are
necessary to establish islet transplantation using DCD.
PMID- 25131089
TI - Islet oxygen consumption rate dose predicts insulin independence for first
clinical islet allotransplants.
AB - BACKGROUND: Human islet allotransplantation for the treatment of type 1 diabetes
is in phase III clinical trials in the U.S. and is the standard of care in
several other countries. Current islet product release criteria include viability
based on cell membrane integrity stains, glucose-stimulated insulin release, and
islet equivalent (IE) dose based on counts. However, only a fraction of patients
transplanted with islets that meet or exceed these release criteria become
insulin independent following 1 transplant. Measurements of islet oxygen
consumption rate (OCR) have been reported as highly predictive of transplant
outcome in many models. METHOD: In this article we report on the assessment of
clinical islet allograft preparations using OCR dose (or viable IE dose) and
current product release assays in a series of 13 first transplant recipients. The
predictive capability of each assay was examined and successful graft function
was defined as 100% insulin independence within 45 days post-transplant. RESULTS:
OCR dose was most predictive of CTO. IE dose was also highly predictive, while
glucoses stimulated insulin release and membrane integrity stains were not.
CONCLUSION: OCR dose can predict CTO with high specificity and sensitivity and is
a useful tool for evaluating islet preparations prior to clinical human islet
allotransplantation.
PMID- 25131090
TI - Human islet viability and function is maintained during high-density shipment in
silicone rubber membrane vessels.
AB - BACKGROUND: The shipment of human islets (IE) from processing centers to distant
laboratories is beneficial for both research and clinical applications. The
maintenance of islet viability and function in transit is critically important.
Gas-permeable silicone rubber membrane (SRM) vessels reduce the risk of hypoxia
induced death or dysfunction during high-density islet culture or shipment. SRM
vessels may offer additional advantages: they are cost-effective (fewer flasks,
less labor needed), safer (lower contamination risk), and simpler (culture vessel
can also be used for shipment). METHOD: IE were isolated from two manufacturing
centers and shipped in 10-cm(2) surface area SRM vessels in temperature- and
pressure-controlled containers to a distant center after at least 2 days of
culture (n = 6). Three conditions were examined: low density (LD), high density
(HD), and a microcentrifuge tube negative control (NC). LD was designed to mimic
the standard culture density for IE preparations (200 IE/cm(2)), while HD was
designed to have a 20-fold higher tissue density, which would enable the culture
of an entire human isolation in 1-3 vessels. Upon receipt, islets were assessed
for viability (measured by oxygen consumption rate normalized to DNA content
[OCR/DNA)]), quantity (measured by DNA), and, when possible, potency and function
(measured by dynamic glucose-stimulated insulin secretion measurements and
transplants in immunodeficient B6 Rag(+/-) mice). Postshipment OCR/DNA was not
reduced in HD vs LD and was substantially reduced in the NC condition. HD islets
exhibited normal function postshipment. Based on the data, we conclude that
entire islet isolations (up to 400,000 IE) may be shipped using a single, larger
SRM vessel with no negative effect on viability and ex vivo and in vivo function.
PMID- 25131091
TI - Clinical porcine islet xenotransplantation under comprehensive regulation.
AB - BACKGROUND: Xenotransplantation with porcine islets is a promising approach to
overcome the shortage of human donors. This is the first report of phase 1/2a
xenotransplantation study of encapsulated neonatal porcine islets under the
current framework of regulations for xenotransplantation in New Zealand. METHODS:
Newborn piglets were anesthetized and bled, and the pancreata were removed with
the use of sterile technique and processed. Encapsulated neonatal porcine islets
were implanted with the use of laparoscopy into the peritoneal cavity of 14
patients with unstable type 1 diabetes without any immunosuppressive drugs. The
patients received encapsulated islets of 5,000 (n = 4; group 1), 10,000 (n = 4;
group 2), 15,000 (n = 4; group 3), or 20,000 (n = 2; group 4) islet equivalents
per kg body weight. Outcome was determined from adverse event reports, HbA1c,
total daily insulin dose, and frequency of unaware hypoglycemic events. To assess
graft function, transplant estimated function (TEF) scores were calculated.
Sufficient or marginal numbers of encapsulated neonatal porcine islets were
transplanted into streptozotocin-induced diabetic B6 mice as an in vivo
functional assay. RESULTS: There were 4 serious adverse events, of which 3 were
considered to be possibly related to the procedure. Tests for porcine endogenous
retrovirus DNA and RNA were all negative. The numbers of unaware hypoglycemia
events were reduced after transplantation in all groups. Four of 14 patients
attained HbA1c <7% compared with 1 at baseline. The average TEF scores were 0.17,
0.02, -0.01, and 0.08 in groups 1, 2, 3, and 4 respectively. The in vivo study
demonstrated that a sufficient number of the transplanted group reversed diabetes
with positive porcine C-peptide. CONCLUSIONS: Transplantation of encapsulated
neonatal porcine islets was safe and was followed by a reduction in unaware
hypoglycemia events in unstable type 1 diabetic patients. The mouse in vivo
assessment data demonstrated certain graft function.
PMID- 25131092
TI - Pancreatic islet autotransplantation after completion pancreatectomy for
pancreatic fistula after hemipancreatoduodenectomy for carcinoma.
AB - OBJECTIVE: Pancreatic islet autotransplantation (IAT) has a potential to prevent
brittle diabetes in patients after total pancreatectomy. Because of the fear of
tumor spread, IAT has rarely been used in case of malignancy. We report our
experience with patients who underwent hemipancreatoduodenectomy for carcinoma
and later completion pancreatectomy for pancreatic fistula with islet
autotransplantation at our institution. METHODS: From August 2007 to December
2012, 5 patients underwent IAT after completion pancreatectomy for pancreatic
fistula after hemipancreatoduodenectomy for carcinoma. Islets were isolated from
the pancreatic tail with the use of digestion with collagenase. Nonpurified islet
suspension was infused into the portal vein during surgery. RESULTS: The median
number of islets transplanted was 175,000 islet equivalents (range, 70,000
365,000). One patient died after surgery for reasons unrelated to IAT. Another 3
patients had stable diabetes with partial graft function (fasting C-peptide
levels 0.23, 0.41, and 0.61 nmol/L and HbA1c 4.8%, 4.6%, and 6.9% at 24, 24 and 9
months after IAT, respectively). The 1st patient, with pancreatic head carcinoma,
was alive 28 months after IAT with lymph node and liver recurrence since 18
months after IAT. The 2nd patient, with gall bladder and distal bile duct
carcinoma, died 47 months after IAT with tumor recurrence. The 3rd patient, with
ampullary carcinoma, died 12 months after IAT with local recurrence and solitary
liver metastasis. The last patient had been off insulin 9 months after IAT
without tumor recurrence (fasting C-peptide, 0.89 nmol/L; HbA1c, 4.2%).
CONCLUSIONS: Autotransplantation of pancreatic islets isolated from the residual
pancreatic tissue in patients who previously underwent hemipancreatoduodenectomy
for cancer may provide stable glucose control and thus improve quality of life.
In this small series we did not observe early development of multiple liver
metastases caused by islet suspension contamination with malignant cells.
Oncologic outcome of the patients was not worse than what would be expected
without IAT.
PMID- 25131093
TI - Xenograft of microencapsulated Sertoli cells for the cell therapy of type 2
diabetes mellitus in spontaneously diabetic nonhuman primates: preliminary data.
AB - Insulin resistance in type 2 diabetes mellitus (T2DM) may be due to a chronic
inflammation of the visceral adipose tissue (VAT) leading to local and systemic
increases in proinflammatory cytokines. Microencapsulated porcine Sertoli cells
(MC-pSC), by provision of immunomodulatory and trophic factors, have been
successfully used to reduce such inflammation in rodent animal models of type 1
diabetes with no complications or deleterious side effects. Herein, we have begun
to investigate this novel and safe therapeutic approach in the spontaneously
obese nonhuman primate with spontaneous, insulin-dependent T2DM. After MC-pSC
intraperitoneal injection we have evaluated, throughout a 6-month follow-up
period, daily ad libitum fed glucose levels, daily exogenous insulin
supplementation, biweekly body weight measurements, periodic fasting blood
glucose concentrations, glycated hemoglobin (HbA1c) levels, glucose tolerance
tests (GTT), and fluorescence-activated cell sorting cytometry (FACS) assessment
of peripheral blood mononuclear cells. Very preliminarily, we have observed a
slight reduction in fasting (FPG) and mean nonfasting (NF) plasma glucose levels.
We found minimal changes, only in 1 animal, in daily exogenous insulin
requirements and HbA1c levels. Flow cytometric analysis was associated with
decrease in CD8(+) cells only in 1 recipient with a reduction in mean regulatory
T Cells (Treg), whereas interestingly, decrease of B lymphocytes was observed in
both animals. These results may suggest that this novel MC-SC-based
transplantation protocol might possibly impact the metabolic status of T2DM in
higher mammals that are close to humans.
PMID- 25131095
TI - Resistance of spontaneously diabetic Ins2(akita) mice to allograft tolerance
induced by anti-CD154 therapy.
AB - BACKGROUND: Despite ongoing advances in the clinical islet transplant field,
progressive decline in graft function continues to reduce the long-term success
of islet transplantation for restoring euglycemia in type 1 diabetic recipients.
To preserve graft function and avoid the use of chronic immunosuppressive drug
therapy, a key goal is to induce donor-specific immune tolerance to islet
transplants. Preclinical rodent studies of islet transplantation largely utilize
models of diabetes either induced experimentally with beta cell toxins or
spontaneously occurring in strains genetically prone to autoimmune diabetes. In
this study, we sought to determine if chronic, severe hyperglycemia itself,
independent of both beta cell toxins and host autoimmunity, influenced acute
allograft rejection and/or the capacity to induce allograft tolerance. METHOD: To
this end, we studied the response to islet allografts in severely diabetic, non
autoimmune C57Bl/6 Ins2(akita) recipients. RESULTS: Results indicate that
diabetic Ins2(akita) mice display higher levels of blood glucose, show more rapid
acute islet allograft rejection, and are resistant to allograft prolongation
induced with anti-CD154 therapy relative to wild-type littermates rendered
diabetic with streptozotocin. As such, results suggest that severe hyperglycemia
may be an independent risk factor impacting the capacity to induce tolerance to
islet allografts. Thus, Ins2(akita) mice represent a stringent model for
evaluating anti-rejection strategies in the setting of severe metabolic demand on
islet transplants.
PMID- 25131094
TI - Failure to achieve normal metabolic response in non-obese diabetic mice and
streptozotocin-induced diabetic mice after transplantation of primary murine
hepatocytes electroporated with the human proinsulin gene (p3MTChins).
AB - BACKGROUND: A recent study by Chen et al described a therapy for diabetes that
involved electroporation of primary hepatocytes with human proinsulin cDNA,
p3MTChins. Intrahepatic transplantation of treated hepatocytes into
streptozotocin (STZ) murine and porcine models led to euglycemia, weight
maintenance, and normal insulin production. We tested the repeatability of their
basic experiments and transplantation technique and expanded the study to include
an autoimmune model. METHODS: Hepatocytes were isolated from B6 mice,
electroporated with p3MTChins, and glucose-challenged or were injected into
hepatic or spleen parenchyma of STZ-diabetic B6 and non-obese diabetic mice.
Outcomes included survival, serum glucose levels, insulin, and c-peptide release.
Untransfected primary hepatocytes and mice transplanted with these cells served
as controls. RESULTS: p3MTChins-hepatocytes secreted insulin during glucose
challenge, but glucose levels did not change with increasing glucose
concentrations. Direct hepatic injection led to high mortality rates. Mice that
underwent intrasplenic injection survived for >50 days (control = 4 days) and had
a mild but stable improvement in hyperglycemia. C-peptide in both mouse models
was detectable but eventually declined to baseline in the non-obese diabetic
mice. CONCLUSIONS: Hepatocytes can be transfected with p3MTChins to produce human
insulin but may lack the proper glucose-sensing or complex storage and secretion
capabilities that allow for a finely tuned dynamic insulin response. Treatment is
subtherapeutic, and p3MTChins-hepatocyte function may not endure in an autoimmune
model. Without successful preliminary findings, cell therapy involving
electroporation of p3MTChins does not appear to be practical as a therapy for
diabetes and may not be a strategy to pursue at this time.
PMID- 25131096
TI - Back to the reinnervation of the pancreas after transplantation? (Experimental
study on dogs, cats, and rats).
AB - BACKGROUND: Significant functional decrease and sclerosis of the pancreas graft
in late delays cannot only be related to chronic rejection. Any transplantation
leads to graft denervation, which may be an important cause of dysfunction.
Studies concerning graft reinnervation were controversial. PURPOSE OF THE STUDY:
The purpose of this study was to investigate the feasibility and pertinence of a
surgically directed reinnervation (SDR) of denervated/neuro-reflex isolated (NRI)
or autotransplanted (aTx) pancreas. BASIC PROCEDURES: Anatomy of the nerves
penetrating into the pancreas was studied in humans, dogs, cats, and rats.
Surgery and physiological investigations were performed in dogs, cats, and rats.
Nervous conductivity between NRI, NRI+SDR pancreas, and brain was tested. Load
tests with glucose, insulin, and adrenalin were performed; amylase and lipase
were determined in fasted and not fasted animals to evaluate the influence of NRI
and SDR on pancreatic function. Histology was provided. Observation delays were 6
months. MAIN FINDINGS: Anatomic feasibility of SDR in humans and animals was
proved. Models of pancreatic tail NRI and surgical reconstitution of the
interrupted nervous pathways (SDR) were elaborated in animals. The restoration of
the pancreas-brain reflex axis after SDR was electro physiologically proved. As
blood glucose curves after load test, exocrine amylase and lipase determination
have shown that pancreas NRI or aTx leads to an exaggerated reaction to usual
stimulations that may cause the observed graft functional exhaustion in late
delays. SDR shortened the period of the graft neuro-reflex isolation, contributed
to a quick normalization of its function, and prevented its late degradation.
CONCLUSION: SDR was shown to be a simple surgical technique, easily performed
after the graft surgical revascularization. Its functional and morphological
efficiency was tested and proved. Thus, SDR may be recommended in human pancreas
transplantation as pertinent.
PMID- 25131097
TI - Surgical salvage of partial pancreatic allograft thrombosis presenting as
ruptured pancreatic cyst: a case report.
AB - INTRODUCTION: Vascular thrombosis is an important cause of pancreatic graft loss,
and the vast majority is managed using graft pancreatectomy. There are limited
reports and case series of successful salvage of the pancreas allograft. We
describe a case of partial pancreatic allograft thrombosis presenting as ruptured
pancreatic cyst successfully salvaged using a graft distal pancreatectomy.
METHODS: We used descriptive retrospective analysis. RESULTS: A 29-year-old
patient with type 1 diabetes and end-stage renal failure underwent a simultaneous
pancreas kidney transplantation with immediate graft function. The cadaveric
pancreas allograft was placed head up in the right iliac fossa with enteric
exocrine drainage and standard vascular anastomosis. He presented with
compressive symptoms on his bladder 5 months later, and a computed tomography
(CT) showed a 4-cm cystic lesion in the body and tail of the pancreas allograft.
Spontaneous rupture of the cyst occurred 3 weeks after the initial onset of
symptoms with generalized abdominal pain. He underwent graft distal
pancreatectomy with good recovery. He remains euglycemic, insulin-free with a
normal renal function. Histology of the resected unhealthy graft showed an
arterial thrombus with xanthogranulomatous inflammation and necrosis. CONCLUSION:
Surgical salvage with graft distal pancreatectomy is feasible for partial
pancreatic allograft thrombosis. Cystic lesion in the pancreas is a possible
presentation of vascular thrombosis.
PMID- 25131098
TI - Successful management of a ruptured mycotic pseudoaneurysm following pancreas
transplantation using bovine pericardial patch: a case report.
AB - Arterial mycotic pseudoaneurysms are a rare complication of pancreas
transplantation. Rupture results in catastrophic hemorrhage with a high risk of
mortality. Definitive management is complicated by an extensive arterial defect
within a contaminated surgical field. Synthetic vascular grafts often fail due to
subsequent graft infection whereas primary repair often results in arterial
stenosis. Arterial ligation may be required to prevent exsanguination. A 41-year
old man, type 1 diabetic with associated renal failure, underwent successful
simultaneous pancreas and kidney transplantation. He presented, 9 months
following transplantation, with life-threatening rectal bleeding secondary to a
ruptured mycotic pseudoaneurysm. This was successfully managed with a bovine
pericardial patch (BPP) repair of the arterial defect and enteric diversion
following graft pancreatectomy. He remains well with no vascular insufficiency 18
months following the procedure. A ruptured mycotic pseudoaneurysm following
transplantation carries a significant risk of mortality and represents a surgical
challenge as conventional techniques using synthetic materials often fail due to
the contaminated field. A BPP offers good handling characteristics, excellent
hemostatic properties and a favorable profile of infection risk in comparison
with synthetic grafts. This case highlights its use as a treatment for a post
transplantation ruptured mycotic pseudoaneurysm.
PMID- 25131100
TI - Donor organ shortage crisis: a case study review of a financial incentive-based
system.
AB - INTRODUCTION: Current organ supply system depends on altruistic noncoercive
donation, which has failed to meet the demand of organ transplantation. Providing
financial incentives to donors is one of several approaches to address organ
shortage. However, its feasibility is debatable as it relates to medical,
ethical, and economic dimensions. An incentive-based procurement system (IBPS)
applied by the Mobile Donor Action Team (MDAT) was instituted in Riyadh, Saudi
Arabia, resulting in a 3-fold increase in donation rate. The goal of this study
was to provide a qualitative review of a 7-year experience with IBPS. MATERIALS
AND METHODS: A qualitative approach was used. Documents were reviewed to create a
chronological audit and shape interview questions. Sampling was purposeful and
inclusive of MDAT members. Semi-structured interviews were conducted, and
findings were subjected to thematic analysis. RESULTS: Documents reflected the
evolution of MDAT. The essence of MDAT is field work and liberal use of financial
incentives, which resulted in a 3-fold increase in the donation rate. MDAT
members believed that IBPS is the main reason behind this increase. Moreover,
IBPS is viewed as acceptable from a moral, ethical, and religious standpoint,
with a high degree of professional satisfaction. CONCLUSIONS: Theoretical
assumptions doubted the feasibility of IBPS. This real-life experience with IBPS
proved the contrary. The findings may be applicable only to the setting in
Riyadh, Saudi Arabia, however; further research is thus needed to explore its
transferability to other settings. IBPS may be an alternative to altruistic
noncoercive donation and should be piloted in different settings.
PMID- 25131101
TI - Communication with family after loss, in the context of transplantology.
AB - BACKGROUND: Cooperation with a patient is a joint venture, based on a division of
power and authority. Its character is not hierarchical. It assumes that this
power is based on knowledge and experience, which is the opposite of power based
on role or position. The good doctor-patient relationship affects a range of
factors, including the healing process, the possibility of understanding the
causes of a disease and its treatment and in a broader perspective, trust in the
health service, which can in turn have a positive influence on public attitudes
to organ donation. Because consent is presumed in Poland, there is no family
consent requirement for organ donation of a deceased family member. In practice,
however, medical professionals usually strive to get consent from family members,
and in cases of refusal, they will not harvest. The aim of our study was to
answer the following questions: (1) Does the way in which care was provided for
the still-alive patient, as well as the relationship between the doctor and the
patient's family, influence the family's decision to agree to the harvest of the
dead patient's organs? (2) Does previous experience with healthcare institutions
and personnel influence their decision to agree to organ donation? METHODS:
Research was conducted on a group of 173 people, using a questionnaire comprising
18 questions. RESULTS: Obtained results show that 34% of people are satisfied
with the level of medical care. The majority claim that doctors treat them
without due care. Thirty-eight percent believe that doctors are capable of
stopping therapy in order to get organs for transplantation. CONCLUSIONS: It is
necessary to recognize the correlation between a correct doctor-patient
relationship, gaining trust, and how reliable a doctor's opinions are. A
patient's conviction that he or she is well treated may lead to regaining the
belief in the straightforwardness of the doctor's opinion, and less
dissatisfaction with and less criticism of medical care.
PMID- 25131102
TI - Organ donation: new hope through the expected amendment in Germany?
AB - INTRODUCTION: The current organ donor shortage in Germany results in the death of
1000 patients on the transplant waiting list every year. In response, a recent
amendment to the German Transplant Act aiming to increase donor rates was passed.
Among a number of other measures, Germans are asked to decide whether they choose
to donate organs or not in the event of a brain death or whether they would like
to designate someone who should decide for them in this situation. The objective
of this study was to collect and evaluate data on the public's attitude toward
organ donation before the expected amendment. METHODS: A survey on the subject of
organ donation was conducted in 2011 among clients of a public pharmacy in a
major city in the federal state North Rhine-Westphalia, Germany. Data regarding
sex, age, health behavior, and attitude toward the amendment were collected and
association organ donor card possession was analyzed. RESULTS: A total of 1485
questionnaires were evaluated. Of those surveyed, only 14.1% had an organ donor
card. No statistically significant associations between sex (P value .3045), age
(P value .1453) and the possession of a donor card were observed. We found that
72.5% of respondents stated that they appreciated the expected amendment, and in
the case of implementation, the majority would obtain an organ donor card.
DISCUSSION: The future success of transplantation medicine relies on an increase
in the public's overall willingness to donate organs. Educating the public and
ensuring transparency in transplantation medicine are vital to achieving higher
donation rates. The new German transplantation act may be an important step to
increase society's awareness and participation in organ donation.
PMID- 25131103
TI - Islamic founding principles on organ transplantation and the evolution of Islamic
scholarly opinions on the subject.
AB - BACKGROUND: Muslims constitute about one-fourth of the human population, and a
significant fraction of the organ recipients identify themselves as Muslims. A
large fraction of the Muslim population is devout but unclear regarding the
religious principles on organ donation and transplantation and is dependent on
scholars' and imams' opinions. METHODS: The Qur'an, the authentic Prophetic
Traditions, and expert opinions on the subject were investigated. RESULTS: The
sources of the Islamic founding principles on organ donation and transplantation
are the Qur'an, the Prophetic Traditions, Usulul Fiqh or expert opinions based on
the Qur'an and Traditions, and Maslaha or the principles of public interest
deduced by the scholars. Some Muslim scholars, mostly from the Indian
subcontinent, opine that live organ donation, extraction of organs from dead
persons, and transplantation are prohibited. Many Arab scholars and Muslim
scholars settled in the western hemisphere opine that live organ donation, organ
extraction from dead persons, and transplantation are permitted, but organ
donation must be a voluntary act of charity. Of late, the Iranian imams/scholars
have recognized that the national government may acquire live donor organs for a
uniform compensation and equitably distribute the acquired organs to patients
with failing organs. CONCLUSIONS: The current Islamic working principles on
transplantation medicine are nonuniform, transitory, and somewhat detached from
the bulk of the population. How such heterogeneity is affecting transplantation
medicine, and organ donation in particular, among Muslim populations warrants
further investigation.
PMID- 25131104
TI - Motivation for organ donation among college students in the United States.
AB - BACKGROUND: The majority of the patients presently waiting for an organ are
waiting for a kidney. Living kidney donation by about 0.1% of the adult
population of a nation may completely eliminate kidney shortage. We investigated
the concerns of college students toward charitable and compensated organ
donation. METHODS: A 40-question survey was conducted. The respondents were
students of the Biology Department of Utah Valley University, Orem, Utah, United
States. The data were tabulated and analyzed. Tests of association among
potentially linked attributes and the difference between two independent
proportions were performed at the 0.05 level of significance and P-values were
also calculated using XLSTAT software. RESULTS: The participants (n = 321) were
47% male, 53% female, 89% Caucasian, and 93% healthy, and 7% of the respondents
had some health conditions. Of the respondents, 55% were ages 18 to 25 and 40%
were ages 26 to 50 years; 43% were unmarried or single, 57% were married, and 85%
had health insurance. About 65% of the respondents lived in small cities and the
rest lived in large cities (23%) or the countryside (9%). There was no
significant association between gender, level of education, location of living,
and household income in relation to belief in organ donation with or without
compensation, except that males favored compensated organ donation over females
(P = .004). Rumors on organ theft and extraction of organ from questionable brain
dead patients had not negatively affected the decision of participants on being
listed as organ donors in their driver's license (P = .0001). Those who
considered organ donation ethically acceptable also believed that a person has
the right to sale a kidney (P = .015) and the donor party should be somehow
compensated (P = .001). CONCLUSIONS: A large percentage of college students
supports compensated organ donation and considers that compensation will increase
organ donation.
PMID- 25131105
TI - Heart donation in Japan before and after the revision of the Japanese
Transplantation Act.
AB - INTRODUCTION: After the revision of the Organ Transplant Act in July 2010, brain
dead organ donation increased from 13 to 45 per year, and heart donation
increased. The purpose of this study was to review 166 consecutive brain dead
heart donors to evaluate our strategies to identify and manage organ donors.
METHODS: This study reviewed 166 consecutive brain dead heart donors since the
Act was issued. Whereas 69 heart donations were performed between October 1997
and July 2010 before the revision of the Act, 97 heart donations were performed
for the 3 years after the revision. Since November 2002, special transplant
management doctors were sent to donor hospitals to assess donor organ function
and to identify which organs could be transplanted. They also intensively cared
for the donors to stabilize hemodynamics and to improve cardiac function by
giving intravenous antidiuretic hormones and by pulmonary toileting via
bronchofiberscope. RESULTS: The mean heart donor age increased from 41.0 to 43.9
years after the revision. Notably, 11 hearts from donors more than 60 years old
were transplanted successfully after the revision. Before the revision, the cause
of death was 37 cerebrovascular disease (SAH 34, stroke 1, bleeding 2), 18 head
trauma, 13 asphyxia, and 2 postresuscitation brain damage. After the revision,
there were 49 cerebrovascular disease (SAH 37, stroke 2, bleeding 16, and other
4), 17 head trauma, 10 asphyxia, and 11 postresuscitation brain damage. A total
of 58 donors had a history of cardiac arrest, 58 required a high dose of
catecholamine drip infusion, and only 1 recipient died of primary graft
dysfunction. Patient survival rate at 3 years after heart transplantation was not
different before and after the revision of the Act (98.6% vs 92.2%). CONCLUSIONS:
Although donor age was increased and donors who died of cerebral bleeding or
postresuscitation after the revision of the Act increased, the outcome after
heart transplantation was not changed.
PMID- 25131106
TI - Regional variation in organ donation in Saudi Arabia.
AB - INTRODUCTION: There is marked regional variation in organ donation among the
different regions of Saudi Arabia. Our aim was to study the dominating factors
for these variations to improve organ donation in low-donation areas. MATERIALS
AND METHODS: This study was a retrospective review of the Saudi Center for Organ
Transplantation data for cadaveric organ donation from 2006 to 2012, with the
number of cases reported, documented, consented, and harvested in various regions
(northern, southern, eastern, western, and central). The region, number, and size
of contributing intensive care units (ICUs), overall donation rate, and
transplanted rate (potential donor and those harvested, respectively) were also
reviewed. RESULTS: Between 2006 and 2012, a total of 512 cases were procured and
analyzed from Saudi Arabia. From the central region, 393 were acquired,
representing 76.7% of the total consented cases. These 393 cases came from 30 of
97 contributing ICUs (31%). The eastern region was ranked second, followed by the
western region. The conversion rate for all regions followed a similar trend.
CONCLUSIONS: There is marked variation with regard to organ donation in different
regions throughout Saudi Arabia, from 1.9% in the southern region to 76.7% in the
central region. This finding is related to the presence of a Mobile Action Donor
Team in the central region. The number of potential donors and the contributing
ICUs were strong predictors of the number of actual donors. We suggest that
having a mobile donor team in each region will increase the number of donors by
at least 3 times within the next 3 to 5 years.
PMID- 25131107
TI - Successful international collaboration improves family donation conversations
resulting in increased organ donation.
AB - INTRODUCTION: Australian donation leaders recognized that to increase organ
donation outcomes, health professionals conducting family donation conversations
(FDCs) required support and specialist training. An international training
institute with programs based on proven results was engaged to create and
implement a customized training program to influence change in FDC practice and
culture. The goal was to increase donation rates by developing and implementing a
customized, self-sustaining training program to enhance FDC practices of health
professionals. Other goals included providing training and communications skills
to lead FDC, supporting families in making decisions, and influencing health
professionals to adopt FDC practices. MATERIALS AND METHODS: To gain support and
determine program suitability, two 1-day pilot training sessions were provided to
45 Australian donation leaders in 2011. Training was further customized with an
emphasis on creating changes to achieve and sustain desired results. A
comprehensive national training plan was implemented over 18 months. Twenty-six 2
day FDC training workshops were held in 8 cities (646 participants). Program
evaluations and debriefings showed distinct shifts in perspectives and an
enthusiasm to implement new processes. In 2012 to 2013, an instructor program was
developed to transition training facilitation. The training institute remains
involved in development and training to build and sustain skill and expertise.
RESULTS: There was a 58% increase in organ donors in Australia from 2009 to 2013
(data reflect 2013 Australian end-of-year organ donation information). This
represents a 36% increase in organ donors (2009-2011); the remaining 22% increase
was achieved in the 2 years since the FDC training was implemented in Australia
(2011-2013). CONCLUSIONS: Improved skills training in the conduct of FDCs seem to
have contributed to improved donation outcomes in national identification,
request, and consent rates. The integration of another organization's process
poses distinct challenges; thoughtful collaboration, sensitive to cultural
aspects and family care, communication, and donation practices, can result in
successful customized training that shifts perspectives, provides new skills, and
achieves and sustains an increase in organ donation rates.
PMID- 25131108
TI - In-house coordination for organ donation--single-center experience in a pilot
project in Germany (2006 to 2013).
AB - A challenge for solid organ transplantation in Germany is the shortage of organs.
In an effort to increase donation rates, some federal states mandated hospitals
to install transplantation officers to coordinate, evaluate, and enhance the
donation and transplantation processes. In 2009 the German Foundation for Organ
Transplantation (DSO) implemented the In-House Coordination Project, which
includes retrospective, quarterly, information technology-based case analyses of
all deceased patients with primary or secondary brain injury in regard to the
organ donation process in maximum care hospitals. From 2006 to 2008 an analysis
of potential organ donors was performed in our hospital using a time-consuming,
complex method using questionnaires, hand-written patient files, and the hospital
IT documentation system (standard method). Analyses in the In-House Coordination
Project are instead carried out by a proprietary semiautomated IT tool called
Transplant Check, which uses easily accessible standard data records of the
hospital controlling and accounting unit. The aim of our study was to compare the
results of the standard method and Transplant Check in detecting and evaluating
potential donors. To do so, the same period of time (2006 to 2008) was re
evaluated using the IT tool. Transplant Check was able to record significantly
more patients who fulfilled the criteria for inclusion than the standard method
(641 vs 424). The methods displayed a wide overlap, apart from 22 patients who
were only recorded by the standard method. In these cases, the accompanying brain
injury diagnosis was not recorded in the controlling and accounting unit data
records due to little relative clinical significance. None of the 22 patients
fulfilled the criteria for brain death. In summary, Transplant Check is an easy
to-use, reliable, and valid tool for evaluating donor potential in a maximum care
hospital. Therefore from 2010 on, analyses were performed exclusively with
Transplant Check at our university hospital.
PMID- 25131109
TI - Exchange of best practices within the European Union: surgery standardization of
abdominal organ retrieval.
AB - Considering the growing organ demand worldwide, it is crucial to optimize organ
retrieval and training of surgeons to reduce the risk of injury during the
procedure and increase the quality of organs to be transplanted. In the
Netherlands, a national complete trajectory from training of surgeons in
procurement surgery to the quality assessment of the procured organs was
implemented in 2010. This mandatory trajectory comprises training and
certification modules: E-learning, training on the job, and a practical session.
Thanks to the ACCORD (Achieving Comprehensive Coordination in Organ Donation)
Joint Action coordinated by Spain and co-funded under the European Commission
Health Programme, 3 twinning activities (led by France) were set to exchange best
practices between countries. The Dutch trajectory is being adapted and
implemented in Hungary as one of these twinning activities. The E-learning
platform was modified, tested by a panel of Hungarian and UK surgeons, and was
awarded in July 2013 by the European Accreditation Council for Continuing Medical
Education of the European Union of Medical Specialists. As a pilot phase for
future national training, 6 Hungarian surgeons from Semmelweis University are
being trained; E-learning platform was fulfilled, and practical sessions,
training-on-the-job activities, and evaluations of technical skills are ongoing.
The first national practical session was recently organized in Budapest, and the
new series of nationwide selected candidates completed the E-learning platform
before the practical. There is great potential for sharing best practices and for
direct transfer of expertise at the European level, and especially to export this
standardized training in organ retrieval to other European countries and even
broader. The final goal was to not only provide a national training to all
countries lacking such a program but also to improve the quality and safety
criteria of organs to be transplanted.
PMID- 25131110
TI - Study of education program of in-hospital procurement transplant coordinators in
Japan.
AB - BACKGROUND: As the number of donated organs is still extremely small in Japan
compared with other developed countries, in-hospital procurement transplant
coordinators (In-Hp PTC) may play an important role in increasing organ donation
and making the procurement procedure smoother. In this study, our education
program of In-Hp PTC is described. MATERIALS AND METHODS: In May 2012, our
department started the In-Hp PTC Education Program. In the first semester, a 2
hour lecture is provided every 2 weeks for 5 months to 15 In-Hp PTCs working near
Osaka. In the second semester, 20 lectures were provided for 3 consecutive days
to 31 In Hp PTCs, more than 80% of whom work far from Osaka. Lecture topics were
the history and current status of organ donation in Japan, social regulation of
organ donation, care of transplant recipients, overall procedures of organ
donation, the role of In-Hp PTC, donor family care, donor indications, and donor
assessment and management. Lectures also included simulations of the organ
donation process. RESULTS: Participants were surveyed for their opinions after
the program, Most participants were satisfied with the program, topics and
duration. As most of them are not full-time In-Hp PTCs, they preferred to attend
the 3-day program. Many participants are currently working as main In-Hp PTCs and
establishing their own organ donation system in their hospital. CONCLUSIONS: In
Hp PTCs have an important role to play in establishing an organ procurement
system and increasing organ donation in Japan. This program may help establish a
systematic education program for this occupation in Japan.
PMID- 25131111
TI - The impact of interleukin 12B (1188A>C), interleukin 16 (-295T>C), and
interleukin 18 (607C>A, 137G>C) gene polymorphisms on long-term renal transplant
function and recipient outcomes.
AB - BACKGROUND: Inflammatory mediators play an important role in kidney graft
outcome. The cytokine and chemokine gene polymorphisms are associated with
variable production, activity, expression, or ligand-receptor affinity. Genetic
variation in the DNA sequence of the interleukin 12B (IL12B), interleukin 16
(IL16), and interleukin 18 (IL18) genes may lead to altered cytokine production
and activity. These variations can lead to changes in individual patient outcomes
after kidney transplantation. It is known that polymorphisms of interleukins have
an influence on inflammatory diseases, eg, Crohn's disease, diabetes, and asthma.
AIM: The aim of this study was to evaluate the correlation between IL12B, IL16,
and IL18 gene polymorphisms with delayed graft function (DGF), acute rejection
episodes (AR), and chronic rejection episodes (CR). MATERIALS AND METHODS: A
total of 267 (38.6% women, 61.4% men) recipients were included in the study.
Cadaveric kidney transplantations were performed at the Department of General
Surgery and Transplantation. Polymerase chain reaction was used to determine gene
polymorphisms of IL12B (rs3212227), IL16 (4778889), and IL18 (rs1946518,
rs187238) in 2 mL of serum. Statistical significance (P < .05) was analyzed by
logit regression, ANOVA and odds ratio (OR) of chi(2) with Yates correction (95%
confidence interval). RESULTS: Regression analysis revealed no significance
between AR/DGF/CR and IL-2B, IL16, IL18rs1946518, and IL18-rs187238 (P > .05).
The CR group, AA vs CC genotype of IL18 (rs1946518), had an OR = 2.35 (P = .04).
AR and DGF groups had no significance in OR. CONCLUSIONS: There was no
statistical significance between IL12B, IL16, and IL18 (rs187238) gene
polymorphisms and kidney graft outcome after transplantation. Presence of AA
genotype (IL18-rs1946518) is connected with a 2.35 times higher risk of CR
occurrence.
PMID- 25131112
TI - Reuse of a previously transplanted kidney from a deceased donor using Luminex
virtual crossmatching: a case report.
AB - Kidney transplantation is the most desired modality of renal replacement therapy
for patients with end-stage renal disease (ESRD). We have attempted to expand the
organ donor pool through several methods, including the use of expanded donor
criteria. Although previously transplanted kidneys are rarely reused, they can be
suitable for transplantation into patients in need. We report a case of
successful reuse of a previously transplanted kidney from a deceased donor by
means of Luminex virtual crossmatching with the first donor and actual
crossmatching with the second donor.
PMID- 25131115
TI - Histologic evaluation of organ preservation injury and correlation with cold
ischemia time in 13 intestinal grafts.
AB - Lesions produced in the graft mucosa due to harvesting, storage, and implantation
must be graduated to assess the subsequent protocolized biopsy specimens. The aim
is to identify type and intensity of graft mucosal lesions observed immediately
after implantation. Congestion, hemorrhage, microthrombi, neutrophilic
infiltrates, shortening of villi, epithelial detachment, erosion, and crypt loss
were separately evaluated by two pathologists in mucosal biopsy specimens from 13
grafts. Each change was assessed as normal, mild, moderate, or severe and by
splintering the summation of points a global score was designed. Cold ischemia
time was registered. Correlation between the pathologists' evaluations and
between final preservation injury degree and cold ischemia time was determined
using the "index of correlation rho (rho)" (Spearman's test). The same changes
were assessed in 19 biopsy specimens from day 2 to day 6 (3.6 +/- 1.1) to
determine their evolution. Congestion was found in 7 biopsy specimens,
microthrombi in 2, hemorrhage in 4, neutrophils in 6, villous atrophy in 8,
epithelial detachment in 9, erosions in 2 and/or crypt loss in 2. The maximum
degree of preservation injury was expressed as intense congestion and hemorrhage
associated with epithelial detachment and villous atrophy. The global
preservation score was grade 3 in 2 cases, grade 2 in 5, grade 1 in 2, and grade
0 in 4. There was positive correlation (rho = 0.915) in the evaluation between
pathologists (P < .01), total agreement in 9 biopsy specimens, and partial
agreement (only 1 point disagreement) in 4. Mean cold ischemia time was 327 +/-
101 min. (135-480). There was positive correlation (rho = 0.694) between
preservation score and cold ischemia time (P < .01). In the follow-up biopsy
procedures, histological injury decreased by at least one grade in every case.
Additionally, karyorrhexis was observed in 3 grafts and very occasional apoptosis
in 2 others. This scale achieves good reproducibility and allows graduate
preservation injury in intestinal transplantation.
PMID- 25131114
TI - Short- and long-term outcomes of every graft recovered during a multi-organ
procurement procedure including the intestine.
AB - BACKGROUND: The development of intestinal transplant (Tx) programs introduces
thymoglobulin donor treatment as well as an almost complete warm dissection of
the abdominal organs to allocate them to different recipients. Our aim is to
assess the reproducibility and feasibility of the surgical technique of multi
organ procurement with the use of thymoglobulin donor pre-treatment and report
the short- and long-term outcomes of every graft harvested as part of multi-organ
procurement (MTOp), including the intestine. METHODS: Data were collected of all
organs harvested from MTOp, including the intestines allocated to our center from
March 2006 to July 2011. Data from 92 recipients and 116 organs procured from 29
MTOp were analyzed. Twelve hearts, 2 lungs, and 1 cardio-pulmonary block were
transplanted; primary graft dysfunction developed in 4 of the 12 hearts and in
the cardio-pulmonary block. RESULTS: The survival rate was 75% and 100% for
hearts and lungs, respectively. Nineteen livers, 9 kidney-pancreas, 19 kidneys,
and 29 intestines were transplanted. Delayed graft function (DGF) of the pancreas
developed in 3 of 9 kidney-pancreas, and the other 3 exhibited DGF of the kidney;
4 of 19 Tx kidneys had DGF. The survival was 84%, 78%, 95%, and 65.5% for livers,
kidney-pancreas, kidneys, and intestines, respectively. CONCLUSIONS: Organs
procured during MTOp including the intestine can be safely used, increasing organ
availability and transplant applicability without compromising allocation,
quality, and long-term results of the non-intestinal-procured organs.
PMID- 25131116
TI - Histologic evaluation of post-implantation immediate C4d deposition in 13
intestinal grafts: correlation with cell-based crossmatching, cold ischemia time,
and preservation injury.
AB - C4d deposits are predictive of humoral rejection in kidney and heart
transplantation. The aim of this study was to identify C4d deposit patterns in
intestinal mucosa of the grafts on biopsy specimens obtained immediately after
implantation and to detect if it could be a valuable tool to predict humoral or
acute rejection. A second objective was to search for a statistically significant
relationship between positive C4d deposition and other collected variables.
Thirteen immediately post-transplantation mucosal graft biopsy specimens,
formalin fixed, underwent immunohistochemical stain for C4d deposits. Diffuse
intense staining of capillary endothelium was considered positive and absent,
focal or weak stains as negative. Preservation injury grade and cold ischemia
times were registered for each case. Donor-specific preformed antibodies were
detected by complement dependent cytotoxicity serologic technique
(crossmatching). Another 19 endoscopic follow-up biopsy specimens from days 2 to
6 were also evaluated. Statistical studies were made using the index of
correlation rho (Spearman's test). Diffuse intense C4d deposits were observed in
2 grafts, focal and weak in 5, and completely negative in 6. The mean cold
ischemia time was 327 +/- 101 minutes. Two cases showed diffuse positive
deposits, 1 had a positive crossmatch and the cold ischemia time was 360 minutes
whereas the other had not preformed antibodies and its cold ischemia time was 475
minutes. Humoral or acute rejection was not observed in follow-up mucosal biopsy
specimens. There was no statistically significant relationship between the C4d
deposition, cold ischemia time, crossmatching results, and preservation injury
degree. In conclusion, C4d deposition was not a helpful tool for diagnosis of
humoral rejection and prediction of acute rejection during the early post
transplantation period.
PMID- 25131117
TI - A surgical perspective of the outcome of a multidisciplinary intestinal
rehabilitation program for children with short bowel syndrome in The Netherlands.
AB - AIM: In 2001, a multidisciplinary intestinal rehabilitation program, prompted by
a nationwide collaboration on intestinal failure (Dutch Registry for Intestinal
Failure and Intestinal Transplantation), was started for children who have short
bowel syndrome (SBS). This study evaluates this program, focusing on children who
have SBS after extensive bowel resection. DESIGN: This is a retrospective cohort
study. METHOD: Demographic data, general information on disease status, and
outcome of intestinal rehabilitation of patients treated between 2001 and 2009
were collected. Outcome measures were intestinal autonomy, intestinal and/or
liver transplantation, and survival. RESULTS: Ten boys and 9 girls, median
gestational age 36 weeks, were treated. Eight were referred, 3 times as many as
in the period 1991-2000. Causes of SBS were intestinal atresia (3), gastroschisis
(2), volvulus (9), necrotising enterocolitis (3), and strangulation (2). The
median remaining small-intestinal length was 35 cm (range, 10 to 70 cm). In 14
patients the ileocecal valve was still present. In all patients at least 25% of
colon was still present. The median follow-up was 25 months (range, 50 days to 9
years). After a median of 138 days (range, 41 days to 11 years) on total
parenteral nutrition, 16 patients (84%) reached intestinal autonomy. Central
venous catheter-related complications occurred in all; there were liver function
disorders in 68%, and a failure to thrive in 26%. One patient underwent
intestinal lengthening. No patient needed intestinal transplantation, but one
underwent liver transplantation for intestinal failure-associated liver disease.
Overall mortality was 11%: those 2 patients died of abdominal sepsis. CONCLUSION:
This specialized intestinal rehabilitation program led to intestinal autonomy in
84% of the patients who had SBS. None of the patients underwent an intestinal
transplantation.
PMID- 25131118
TI - Quality of life and performance status before and after small intestinal
transplantation.
AB - INTRODUCTION: Intestinal transplantation (IT) is considered for patients with
irreversible intestinal failure who develop life-threatening complications of
parenteral nutrition or have extensive intra-abdominal disease requiring
evisceration. Developing indications may include quality of life (QOL)
considerations and therefore assessment of QOL and performance status (PS) after
IT is important. We report QOL and PS before and after IT in our cohort. METHODS:
Consecutive patients undergoing IT were included. QOL was assessed using the
generic 36-item short form survey (SF 36) tool at assessment and 6-month
intervals post-transplantation. Performance was assessed using a visual analogue
scale (VAS), Karnofsky scale (KS), and the Eastern Cooperative Oncology Group
scale at three time points: premorbidly, at listing, and after transplantation.
RESULTS: Data were available for 21 patients. There were 11 complete SF 36
datasets and 15 performance scores. Data were not available from 3 patients, and
the overall response rate was 62%. Overall, there was a trend for improved SF 36
scores post-transplantation in approximately half of the patients with scores
remaining stable in approximately one third. The results of the SF 36
significantly improved in 1 patient (P < .01). After IT, 66% of patients had
better VAS scores than at listing and >75% of patients scored better or the same
in KS compared to status at listing. However, PS after IT did not improve to
premorbid levels. CONCLUSION: We found a trend for QOL scores to improve in
approximately half of the patients compared to their status at listing, remain
static in approximately one third, and a minority experience a decline. For the
majority, differences were not statistically significant. PS of patients after
transplantation is equal or better than that at listing in 75%, but rarely
reaches that of the premorbid status. Longer-term studies are needed and may
reveal progressive improvement.
PMID- 25131119
TI - Adult small intestinal and multivisceral transplantation: lessons through the
"retrospecto-scope" at a single UK centre from 1991 to 2013.
AB - The first intestinal transplantation in the United Kingdom was performed in
Cambridge in 1991. Thirty-eight intestinal transplantations have since been
performed in 35 patients. All deaths in the first postoperative month related to
hemorrhage, in 2 cases to severe portal hypertension (SPH) and poor venous access
in 2. We have modified our practice to reduce the bleeding risk with SPH. Loss of
venous access can be avoided by timely referral. Rejection was implicated in 3/14
deaths all dying of sepsis. Cytomegalovirus disease resulted in 2 deaths; we try
to avoid CMV-positive donors giving to CMV-negative recipients. Three deaths were
related to psychiatric illness, which led to loss of graft in 2 others. Three
patients were retransplanted (2 rejections and 1 infarction) and all remain
alive. Most patients (10/13) experienced a fall in body weight in the first
postoperative year after SB/MV transplantation. Body weight fell by as much as
25%. As transplantation resulted in a net gain in small bowel in most cases, the
postoperative loss of native body weight may be underestimated. Interestingly
this was not associated with a significant fall in midarm circumference or
handgrip strength. Long-term nutrition can be maintained with oral intake in the
majority of patients post-SBT. There is improvement in handgrip strength post
transplant. Transplantation does not significantly alter weight, albumin, or
other common anthropometric markers. Despite these problems, our 5-year survival
results remain relatively good at 73% in the cohort from 1991, 79% from 2003, and
80% from 2008. We consider that deployment of strategies learned from our
experiences has improved outcomes.
PMID- 25131120
TI - Selenium homocholic acid taurocholate scanning, selenium-75-labeled bile acid, a
novel method for testing the function of the terminal ileum in small bowel
transplant recipients: a pilot study.
AB - INTRODUCTION: The terminal ileum (TI) is important for the active reabsorption of
bile salts and is the site of allograft rejection; disruption of enterohepatic
circulation (EHC) may give insights to inflammatory and other physiologic
processes at the TI. SUBJECTS AND METHODS: Four children aged 5 to 12 years who
had received small bowel transplantation (SBTx), 3 recovering from post
transplant lymphoproliferative disease (PTLD) and 1 with acute rejection, were
studied. Two of the 4 had stoma reversal. Another child (15 years) with
progressive familial intrahepatic cholestasis (PFIC) and pruritus, despite liver
transplantation and biliary diversion, was studied. Selenium homocholic acid
taurocholate scanning ((75)SeHCAT) capsule was given orally (n = 3) or via
introducer during endoscopy (n = 2); a baseline whole-body gamma camera scan was
done 4 hours later and on days 1 to 5. RESULTS: The normal 3-day bile salt
retention is 30% to 70% of baseline and normal adult biological half-life, t1/2
is 62 +/- 17 hours. The results in children with a stoma were very low (0.1% at
7.6 hours; 5% at 17 hours). The children with reversed stoma had retention and
t1/2 closer to the reference range (18% at 29 hours; 22% at 33 hours). The child
with PFIC + biliary diversion had an initial very high gamma emission from the
stoma bag suggesting excellent reabsorption of bile salts from his TI, but
retention was 0.6% and t1/2 9.8 hours, demonstrating efficient biliary diversion.
CONCLUSION: These results confirm children with stomas malabsorb bile acids,
which can be ameliorated after stoma closure. SeHCAT demonstrated that the
biliary diversion was working well and may be helpful in preoperative assessment
of abnormal EHC. The role of SeHCAT in SBTx requires further evaluation.
PMID- 25131121
TI - Impact of intestinal transplantation for intestinal failure in Japan.
AB - INTRODUCTION: The prognosis of intestinal failure has improved dramatically in
the past few decades with the development of parenteral nutrition (PN). However,
PN-dependent patients still have numerous complications. Intestinal
transplantation can significantly improve their prognosis and quality of life. We
report on the impact of intestinal transplantation for intestinal failure in
Japan. METHODS: Intestinal transplantations have been performed in Japan since
1996. Standardized forms were sent to all known intestinal transplantation
programs, asking for information on intestinal transplantations performed between
1996 and June 31, 2012. All programs responded. Patient and graft survival
estimates were obtained using the Kaplan-Meier method and analyzed with the
Wilcoxon statistic. RESULTS: Five institutions provided data on 24 grafts in 21
patients. There were 12 cadaveric and 12 living related donor transplants. Causes
of intestinal failure included short gut syndrome (n = 9), intestinal motility
function disorders (n = 11), retransplantation (n = 3), and other (n = 1). The
overall 1- and 5-year patient survival rates were 86% and 68%, respectively. In
cases (n = 15) after 2006, the 1-year patient survival rate was 92%, and the 5
year survival rate was 83%. One- and five-year graft survival rates were 87% and
78%, respectively. More than 80% of all current survivors discontinued PN.
CONCLUSIONS: Intestinal transplantation has become an effective therapy for
patients with intestinal failure who cannot tolerate PN. After 2006, patient and
graft survival rates approached rates associated with standard treatment for end
stage intestinal failure. Further improvements are expected with early referral
due to suitable donor organ and pretransplant management.
PMID- 25131122
TI - Evaluation of epithelial chimerism after bone marrow mesenchymal stromal cell
infusion in intestinal transplant patients.
AB - Intestinal transplantation is the most effective treatment for patients with
short bowel syndrome and small bowel insufficiencies. We evaluated epithelial
chimerism after infusion of autologous bone marrow mesenchymal stromal cells
(BMSCs) in patients undergoing cadaveric donor isolated intestinal
transplantation (I-ITx). BMSCs were isolated from patients' bone marrow via iliac
puncture and expanded in vitro prior to infusion. Two out of the 3 patients were
infused with autologous BMSCs, and small intestine tissue biopsies collected post
operatively were analyzed for epithelial chimerism using XY fluorescent in situ
hybridization and short tandem repeat polymerase chain reaction. We observed
epithelial chimeric effect in conditions both with and without BMSC infusion.
Although our results suggest a higher epithelial chimerism effect with autologous
BMSC infusion in I-ITx, the measurements in multiple biopsies at different time
points that demonstrate the reproducibility of this finding and its stability or
changes in the level over time would be beneficial. These approaches may have
potential implications for improved graft survival, lower immunosuppressant
doses, superior engraftment of the transplanted tissue, and higher success rates
in I-ITx.
PMID- 25131123
TI - Prothrombotic disorders in a cohort of 25 patients undergoing transplantation:
investigation and management implications.
AB - BACKGROUND: Many patients referred for intestinal transplantation have a history
of thrombosis. We undertook an analysis of transplanted patients to describe the
history and frequency of thrombosis, clinical course, and management strategies
used. RESULTS: Twenty-five patients underwent transplantation of intestine
containing blocks between 2007 and 2012; 20 of 25 are still alive. Five of 25
patients were transplanted with history of portomesenteric thrombosis, 6 of 25
had experienced loss of venous access due to thrombosis, and 6 of 25 had history
of mesenteric ischemia. Pretransplantation, 16 of 25 patients were
anticoagulated. Thrombophilia screens identified 3 of 16 patients who were JAK2
positive, 1 of 25 who had antithrombin deficiency, and 1 of 25 who had a factor V
Leiden heterozygote. Post-transplantation, of all 16 patients who were
anticoagulated pretransplantation and continued postoperatively, 1 of 16
infarcted their small bowel graft and 4 of 16 developed a further venous
thrombosis despite anticoagulation. Of the 9 without a previous history of
thrombosis, 1 had a pulmonary embolus more than a decade after transplantation
and another had an upper limb deep vein thrombosis associated with a line. Both
were then anticoagulated. Seven of 25 are not anticoagulated, although they are
administered antiplatelet prophylaxis. Postoperative bleeding complications of
anticoagulation occurred in 3 patients. After a subarachnoid hemorrhage in 1 of
those 3 patients, anticoagulation was stopped. The other 2 patients bled during
ileal biopsy, and both remain on low molecular weight heparin treatment.
CONCLUSION: Those with identifiable thrombophilic tendency and a history of
venous or arterial thrombosis are considered to be at high risk for recurrent
thrombosis. Those without such a history could be considered low risk. Our
practice is to anticoagulate all high-risk individuals before and after
transplantation and offer antiplatelet prophylaxis to low-risk patients as the
risk of anticoagulation probably outweighs the risk of thrombosis for them. Early
input from hematologists is vital in the management of high-risk patients,
particularly those who thrombose when anticoagulated.
PMID- 25131124
TI - Psychiatric disorders in patients undergoing intestinal transplantation.
AB - BACKGROUND: Psychiatric disorders are common in chronic disease states;
intestinal transplantation recipients may therefore be at high risk for
psychiatric disorder (PD). We sought to investigate the frequency and type of PD
in our cohort of patients undergoing transplantation between 2007 and 2012.
RESULTS: The notes of 25 patients who had undergone transplantations since 2007
were available for analysis. Five of 25 patients had died at the time of data
collection. Pretransplantation, 14 of 25 patients had a history of a single
psychiatric disorder (SPD) (depression). Two of 25 had double psychiatric
diagnoses (DPD; depression with anxiety), and 1 had three PDs. Three of 25
patients suffered from chronic pain syndrome and 1 patient had this as an
isolated diagnosis without any other PD. Post-transplantation, 10 of 14 patients
still had an SPD; however, 3 of 14 had acquired a second diagnosis (DPD; anxiety
with depression) with suicidal ideation in 2 cases. Those with DPD preoperatively
did not improve. Depression resolved in 1 of 14 after transplantation. One
patient without a history of psychiatric issues developed DPD during the
postoperative course. Only 3 of 25 surviving patients are free of any
psychological diagnosis post-transplantation. The presence of other problems in
the cohort such as chronic pain syndrome in 4 of 25, medical noncompliance in 3
of 25, cyclizine dependency in 2 of 25, and recreational drug use suspected in 1
were also identified. Problems with body image relating to the stoma were
experienced by 2 of 25 patients. CONCLUSION: The incidence of psychiatric
disorder in patients embarking on transplantation is high and relates to their
history of chronic illness. The additional stress of the transplantation
operation and the long in-hospital rehabilitation period takes its toll on
patients' emotional health and many acquire further psychiatric diagnoses.
Managing the psychiatric health of patients is important for successful
rehabilitation and their long-term health and wellbeing.
PMID- 25131125
TI - Renal failure associated with intestinal transplantation: our experience in
Spain.
AB - BACKGROUND: Renal failure (RF) is a frequent complication in non-renal solid
organ transplants. In the present study, we analyze our experience with
intestinal transplants (ITx). METHODS: Between 2004 and 2012, we performed 21 ITx
in 19 adult patients. Alemtuzumab was used as an induction agent followed by
tacrolimus. Renal function was assessed before ITx and during the perioperative
period. RESULTS: The main cause for transplants was non-resectable desmoids
tumors (33.3%), followed by vascular thrombosis (19%) and others. Medical
complications were frequent, especially infectious diseases, which were the most
common (51%). Surgical complications were also frequent, but most of them (>50%)
were mild but leading to a great number of re-operations and prolonged stays in
hospital. Acute rejection is very frequent (66.6%) but mild in more than 70% of
the cases. Finally, RF was very frequent (68.4%; 13/19 patients) and accounted
for 15.6% of all medical complications. Causes were multiple. One patient is
awaiting a kidney transplant, but no other patients need renal replacement
therapy at the moment. Ileostomy closure was performed in 5 of 12 patients alive,
showing improved renal function in 3 of them. CONCLUSIONS: RF is a problem in ITx
and is always multifactorial. Increases in hospital stay, higher morbidity and is
a cause for hospital readmission. Almost all patients had an impaired renal
function when discharged. Immunosuppressants and ileostomy closure as soon as
possible might prevent RF.
PMID- 25131126
TI - The "Pavia model" of experimental small bowel transplantation in pigs: technical
variations for ischemia reperfusion injury studies.
AB - Ischemia reperfusion injury (IRI) is a major field of study in small bowel
transplantation because of its implications regarding intestinal immunity. In
this study, we have introduced some variations to the described models of IRI in
pigs to make possible a complete isolation of the small bowel for IRI studies. In
swine, two anatomical barriers make impossible a complete isolation of the small
bowel at the origin of superior mesenteric artery (SMA) and vein (SMV): the main
colic vessels, which originate distally to form SMA and SMV, and the blood supply
of the distal portion of the duodenum and the cephalic part of the pancreas. In a
group of Large White pigs (n = 5), we have performed a complete isolation of the
small bowel, including sub-total colectomy and pancreaticoduodenectomy. Both SMA
and SMV were isolated at the origin from the aorta and at the junction of the
splenic vein, respectively. Intestinal continuity was restored with
duodenojejunal anastomosis and with ileotransverse colon anastomosis. One pig
died on postoperative day 5 from intestinal occlusion due to adhesions. The
remaining four pigs were killed on postoperative day 7 after an uneventful
postoperative course. No complications were found at autopsy. In swine, resection
of part of the pancreas and duodenum and removal of the large bowel does not
affect short-term survival, allowing a full isolation of the entire small bowel
mimicking the transplantation procedure. Thus, this model appears to be
attractive for IRI studies in the field of intestinal transplantation.
PMID- 25131127
TI - Anti-inflammatory effects of ischemic preconditioning on rat small bowel
allografts.
AB - INTRODUCTION: Minimizing the inflammatory events that follow intestinal
transplantation may influence immediate graft function and improve outcome.
Ischemic preconditioning (IPc) has been shown to ameliorate early inflammatory
responses, and it may also attenuate the potentially damaging inflammation after
intestinal transplantation. Herein, we examine the influence of intestinal IPc on
inflammatory indices (tissue expression of ICAM-1, CD11a, and CD44 and serum
levels of the soluble ICAM-1, sICAM-1) after heterotopic intestinal
transplantation. METHODS: Lewis rats received full-length preconditioned or non
preconditioned Brown Norway intestinal allografts in the absence of
immunosuppression. Preconditioned grafts were subjected to 1 cycle of 10 minutes
of ischemia-reperfusion. Preconditioned and non-preconditioned isografts acted as
controls. Blood was collected on alternate days post-transplant, and graft tissue
harvested on sacrifice. ICAM-1, CD44, and CD11a expression was determined by
immunohistochemistry, and the area of staining was quantified using image
analysis. Serum soluble ICAM-1 levels were determined using an R&D Systems
Quantikine enzyme immunoassay. RESULTS: (1) IPc ameliorated serum levels of sICAM
1 until severe rejection (day 7) overcame this down-regulation when compared to
non-preconditioned allografts (day 3: 34,304 vs 40,479 pg/mL; day 5: 52,441 vs
61,593 pg/mL; day 7: 75,114 vs 73,309 pg/mL; day 9: 72,872 vs 76,314 pg/mL,
respectively). (2) ICAM-1 expression was significantly lower in preconditioned
allografts (1.02 vs 2.01 mm(2)). (3) CD44 tissue levels were also found to be
lower in preconditioned allografts (0.86 vs 1.13 mm(2)). (4) There was a
significant relationship between tissue ICAM-1 expression and serum levels of
soluble ICAM-1 (P < .02). CONCLUSIONS: IPc improves inflammatory indices in the
early stages following intestinal transplantation, and this might lead to a
preserved cellular, architectural, and functional graft status. Furthermore, our
results support the use of soluble ICAM-1 as a marker of endothelial activation,
and thence of inflammation and developing rejection.
PMID- 25131128
TI - Preface: The dawn of the new age. First experiences after being full member of
Eurotransplant.
AB - After so many years of the first initiative, to join the Eurotransplant (ET),
this dream of many experts and professionals has become true. This difficult and
long story was discussed in details and published here as the--prefaces of the
11(th) and 12(nd) Congresses of the Hungarian Transplantation Society. Since
1(st) July 2014 Hungary became a full member of ET. The 15(th) Congress was the
first occasion to summarize the early experience of the membership.
PMID- 25131129
TI - Early histopathological changes in new-onset diabetes after kidney
transplantation.
AB - BACKGROUND: New-onset diabetes after transplantation (NODAT) is one of the most
common complications after kidney transplantation. METHODS: Patients were
randomly assigned to receive cyclosporine A-based or tacrolimus-based
immunosuppression. Fasting and oral glucose tolerance tests were performed, and
the patients were assigned to one of the following 3 groups, on the basis of the
results: normal, impaired fasting glucose/impaired glucose tolerance, or NODAT.
NODAT developed in 14% of patients receiving cyclosporine A-based
immunosuppression and in 26% of patients taking tacrolimus (P = .0002). RESULTS:
Albumin levels were similar, but uric acid level (P = .002) and the age of the
recipient (P = .003) were significantly different between the diabetic and the
normal groups. Evaluation of tissue samples revealed that acute cellular
rejection and interstitial fibrosis/tubular atrophy were significantly different
in the NODAT group. Changes in the Banff score provided significant difference
regarding tubulitis and interstitial inflammation (P = .05). CONCLUSIONS: The
pathological effect of new-onset diabetes after kidney transplantation can be
detected in the morphology of the renal allograft earlier, before the development
of any sign of functional impairment.
PMID- 25131130
TI - Prevalence of obesity and metabolic changes after kidney transplantation:
Hungarian pediatric cohort study.
AB - BACKGROUND: Cardiovascular mortality rate in patients with end-stage renal
disease is 3 magnitudes higher than in the general population; it remains 10-fold
higher after successful renal transplantation (Tx). Among others, obesity and
hypertension can exert deleterious effects on vascular structure and function
after Tx. Successful kidney transplantation may induce excessive weight gain in
part because of the effects of steroid treatment. METHODS: The purpose of this
study was to evaluate the presence of obesity in Tx children, their obesity
related metabolic disturbances, and to assess their blood pressure and arterial
stiffness in relation to obesity. Forty-one transplant children (age, 15.7 [3.5]
years; 28 males) were studied. Body composition was assessed by body mass index
(BMI), waist circumference, skin-fold measurements, and multifrequence
bioimpedance analysis. Glucose metabolism, blood pressure, and arterial stiffness
(with the use of pulse wave velocity) were studied. Age- and sex-dependent
parameters were expressed as standard deviation scores (SDS). RESULTS: The
prevalence of overweight (BMI >85%) increased from 3.2% to 24.4% at 49 months (3
183) (median, range); the BMI SDS increased from -0.27 (0.79) to 0.67 (1.35)
after Tx. There was a close correlation between BMI SDS and the percentage of
body fat and body fat mass in the Tx group (r = 0.80; r = 0.94, P = .0001).
Children with disturbed glycemic control (n = 14) had higher percentage of body
fat and higher blood pressure compared with those with normal glucose metabolism
(P < .05). There was no difference in pulse wave velocity between the lean and
obese patients. CONCLUSIONS: The prevalence of overweight or obese patients in
the Hungarian pediatric renal cohort is low at transplantation and rises
subsequently. Overweight is associated with disturbed glycemic control and
increased blood pressure; however, these disturbances are not yet reflected by
stiffening of the arteries. Strategies are needed to prevent obesity, its impact
on hypertension, and cardiovascular disease in pediatric transplantation.
PMID- 25131131
TI - De novo Prograf versus de novo Advagraf: are trough level profile curves similar?
AB - BACKGROUND: According to the clinical trials, Advagraf (ADV) has efficacy and
safety profile similar to Prograf (PROG). The aim of this study was to compare
the graft functions, dosages, and tacrolimus (TAC) trough level profile curves of
patients on de novo PROG and ADV therapy. METHODS: The ADV group included 39 de
novo renal cases who had received initial immunosuppression (IS) with once-daily
TAC (1 * 0.2 mg/kg from day1 after transplantation). We compared them with a PROG
group of 38 transplant patients who received equivalent IS with twice-daily TAC
(2 * 0.1 mg/kg from day1). In both groups, the IS was combined with
antimetabolites and steroids. The mean follow-up time was similar (13.5 +/- 7
days) in both groups after renal transplantation until the emission of the
patients from our clinic. RESULTS: TAC mean total daily dose was reduced and
whole-blood trough levels decreased over the time in early postoperative days.
Only on day 3 and day 4 after transplant, a significant higher adjustment in the
ADV dosage was necessary to achieve sufficient TAC trough levels. The average TAC
trough level profile curves were similar in PROG and ADV groups, but the
individual curves were very different. Mainly in patients on ADV therapy, the
initial concentrations were often >30 ng/mL, and in some cases on the 9th
posttransplant day decreased to <5 ng/mL, then slowly increased into the required
therapeutic range. CONCLUSIONS: The results demonstrate that patients after renal
transplantation can be safely treated de novo with ADV. Setting the required
therapeutic TAC blood levels may require more attention to avoid the
"fluctuations" of trough level profile curve during the early postoperative
period. Our data suggest that dose adjustment of ADV can be carried out more
carefully compared with PROG on the basis of clinical symptoms and the value of
TAC blood levels to avoid acute rejection and toxicity.
PMID- 25131132
TI - Three-year longitudinal clinical trial of arterial function assessed by a
oscillometric non-invasive method in comparison with carotid sclerosis and
transferrin kidney-transplanted patients.
AB - Chronic kidney disease remains one of the main risk factors of cardiovascular
disease. However, patients with kidney transplantation have better life
expectancy and better quality of life compared with patients on dialysis. In
patients with a well-functioning graft, the main cause of death is cardiovascular
in origin. Metabolic pathways have complex effects on arterial function that can
be monitored by conventional ultrasonography and with the assessment of arterial
stiffness by oscillometric non-invasive technique. Forty-one primer cadaver
kidney-transplanted patient were involved in a 3-year longitudinal clinical trial
(21 female, 20 male; average age, 40.16 +/- 12.56 years). Arterial stiffness
parameters referring to rigidity of the arterial wall (pulse wave velocity [PWV],
augmentation index, and pulse pressure) were investigated. Correlation between
stiffness, and laboratory parameters (serum creatinine, urea, hemoglobin,
albumin, cholesterine, triglycerides, transferrin, uric acid, glomerular
filtration rate, and C-reactive protein) were analyzed. A non-invasive
oscillometric method--Tensiomed Arteriograph--was applied to assess the arterial
stiffness parameters. Statistical analysis was performed with the use of
Statistica for Windows, version 8.0. A value of P < .05 was considered
statistically significant for all statistical tests. We found a positive
correlation between PWV and left ventricular wall thickness and a negative
correlation between PWV and ejection fraction. We also found a positive
significant correlation between serum level of transferrin and PWV. There was
simultaneous significant progression concerning PWV and carotid artery sclerosis
in a 3-year follow-up. There was no fatal cardiovascular event during the study
period among our patients. All of our patients involved in this study are still
alive. Our findings suggest that arterial stiffness monitoring is a reliable
method to assess global cardiovascular risk among kidney-transplanted patients.
The oscillometric method is convenient, fast, painless technique to monitor
arterial function, which, in the case of pathological findings, proposes more
frequent cardiovascular control.
PMID- 25131133
TI - Endogenous thrombin potential and examination of a further 31 analytes in liver
transplant candidates.
AB - BACKGROUND: To predict the change in patient status and differentation of the
basic diseases, endogenous thrombin potential (ETP), clinical chemistry, and
coagulation variables were measured in liver transplant-listed patients with
different etiologies. METHODS: Differences in values of ETP and analytes of 30
control persons and 164 cirrhotic patients were examined by means of binary
logistic regression. The relationship between the analytes and ETP parameters
were analyzed by means of Spearman correlation. The different etiologies of
cirrhosises were studied by factor and discriminant analyses. Binary logistic
regression was applied to forecast changes in clinical status. Survival analysis
was carried out with the appropriate variable. RESULTS: International Normalized
Ratio and activated partial thromboplastin time values were higher, whereas the
area-under-the-curve values were lower in cirrhosis than in healthy subjects. A
strong relationship was found only between the peak height and the anti-thrombin
III (ATIII) values. In the factor analysis, 3 factors were found, which explained
81.6% of the total variance. Combination of aspartate aminotransferase and ATIII
mostly separated the basic disease groups from each other in the discriminant
analysis. From 35 variables, the lactate dehydrogenase (LDH) and ATIII have been
suited for predicting the change in patient status. Eighty percent of patients
with low ATIII and high LDH levels had deterioration of their clinical status.
CONCLUSIONS: Our study demonstrated that the ETP parameters did not provide
additional information compared with "conventional" coagulation tests in
cirrhosis. On the basis of our study, LDH and ATIII appear to be promising
analytes to assess the clinical status of patients with cirrhosis. In our
opinion, the classification system of liver transplant-listed patients can be
improved with their use.
PMID- 25131134
TI - New-onset diabetes mellitus and the analysis of dipeptidyl-peptidase-4 after
liver transplantation.
AB - BACKGROUND: New-onset diabetes mellitus after transplantation (NODAT) is a common
complication after orthotopic liver transplantation (OLT). The diabetogenic
effect of hepatitis C virus (HCV) infection is well known. The aim of this study
was to analyze the glucose homeostasis before and after OLT. The oral glucose
tolerance test (OGTT) was carried out, and dipeptidyl-peptidase-4 (DPP-4)
activity was measured. METHODS: The study period was from 2012 to 2014. We
enrolled 49 non-diabetic patients from the waiting list (group A) and 21 patients
after OLT (group B). Seven patients were monitored continuously both before and
after OLT. According to our preoperative OGTT results, 13 patients in group A had
newly diagnosed diabetes mellitus (group A/DM) and 11 had impaired glucose
tolerance (group A/IGT). In 25 cases, normal glucose tolerance was diagnosed
(group A/NGT). The calculated homeostasis model assessment insulin resistance
(HOMA2-IR) values were both in group A/DM and-IGT higher compared with group
A/NGT (2.42 +/- 0.81 vs 2 +/- 0.98 vs 1.28 +/- 0.67; P = .001). In the case of
HCV infection (n = 14; 29%) DM and IGT were more frequent. RESULTS: Six patients
in group B had NODAT. In 9 cases, IGT and in 6 cases NGT was detected. In the
case of HCV infection (n = 9; 43%), DPP-4 levels were higher compared with that
in patients with all other indications for OLT (15.5 +/- 5.2 vs 8.7 +/- 3.5; P =
.008). We evaluated the same individuals before and after OLT (n = 7), and a
decrease in beta-cell function was noted. CONCLUSIONS: Preoperative OGTT is an
important and easy investigation to rule out glucose imbalance before OLT. The
HOMA2 calculation can also be useful both in preoperative and postoperative risk
assessment. In our results, DPP-4 activity is not specific for the type of
glucose homeostasis imbalance, but, in HCV infection, it is higher. DPP-4
inhibitors can be effective in the therapy of NODAT, especially in HCV-infected
patients.
PMID- 25131135
TI - Effect of setting temperature on glucono-delta-lactone-induced gelation of silver
carp surimi.
AB - BACKGROUND: Setting temperature is important for heat-induced surimi gel
formation. However, there is little information concerning setting temperature on
the properties of glucono-delta-lactone (GDL)-induced surimi gel, which is
considered a new preparation technique. RESULTS: The pH of surimi gel induced by
2% GDL was about 4.6, while the breaking force of GDL-induced surimi gel
preheated at a temperature range of 35-50 degrees C was higher than that of heat
induced surimi gel. The breaking force, deformation and whiteness of GDL-induced
surimi gel were increased with increasing setting temperature from 30 to 45
degrees C, but water-holding capacity was decreased. When setting temperature was
further increased to 50 degrees C, the textural properties were decreased, and
myosin heavy chain (MHC) was degraded slightly. The data of protein subunits
solubilized in various solvents revealed that MHC participated in the formation
of GDL-induced surimi gel mainly through hydrophobic interactions. Furthermore,
when GDL-induced surimi gel was preheated at 45 degrees C, a compact and fine
fiber microstructure was observed by scanning electron microscopy. CONCLUSION:
Setting treatment at the appropriate temperature could promote the formation of a
fine, compact GDL-induced surimi gel network, resulting in improved textural
properties.
PMID- 25131136
TI - Lessons learned from mice and man: mimicking human allergy through mouse models.
AB - The relevance of using mouse models to represent human allergic pathologies is
still unclear. Recent studies suggest the limitations of using models as a
standard for assessing immune response and tolerance mechanisms, as mouse models
often do not sufficiently depict human atopic conditions. Allergy is a
combination of aberrant responses to innocuous environmental agents and the
subsequent TH2-mediated inflammatory responses. In this review, we will discuss
current paradigms of allergy - specifically, TH2-mediated and IgE-associated
immune responses - and current mouse models used to recreate these TH2-mediated
pathologies. Our overall goal is to highlight discrepancies that exist between
mice and men by examining the advantages and disadvantages of allergic mouse
models with respect to the human allergic condition.
PMID- 25131137
TI - Characterisation of tissue transglutaminase-reactive T cells from patients with
coeliac disease and healthy controls.
AB - Previous studies have shown evidence for T lymphocytes specific for tissue
transglutaminase (tTG) in the periphery of coeliac disease (CD) patients. These
cells could play a role in disease pathogenesis and may be involved in providing
help for the production of anti-tTG autoantibodies. The objective of this study
was to further investigate the presence of tTG-specific T cells in patients with
treated and untreated CD, and normal controls. Positive proliferative responses
to three different commercial tTG antigens were detected in all groups tested,
occurring more frequently and at higher levels in untreated CD patients. The
addition of antibodies to HLA-DQ and HLA-DR caused a significant reduction in the
proliferative response to tTG. T cell lines specific for tTG and composed
predominantly of CD4-positive T cells were generated from responsive CD and
control individuals, and were found to produce large amounts of interferon-gamma,
as well as interleukins 10, 17A, and 21.
PMID- 25131138
TI - C-Myc participates in beta-catenin-mediated drug resistance in A549/DDP lung
adenocarcinoma cells.
AB - The aim of this study was to investigate c-Myc and beta-catenin-mediated drug
resistance in A549/DDP lung adenocarcinoma cells. Cisplatin sensitivity was
determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
(MTT) toxicity assay. beta-Catenin and c-Myc protein expression following
cisplatin treatment were determined using western blotting and
immunofluorescence. Flow cytometry was performed to detect cell cycle and
apoptosis in A549, A549/DDP, and c-Myc small interfering RNA (siRNA)-transfected
A549/DDP cells before and after treatment with different doses of cisplatin. The
median inhibitory concentration (IC50 ) in cisplatin-treated A549 and A549/DDP
cells was 5.769 +/- 0.24 MUmol/L and 28.373 +/- 0.96 MUmol/L, respectively; the
cisplatin resistance of A549 cells was about five times that of A549/DDP cells.
Endogenous beta-catenin and c-Myc expression in A549/DDP cells were higher than
that in A549 cells, and were upregulated in A549/DDP cells (p < 0.05) and
downregulated in A549 cells after 48 h cisplatin treatment (p < 0.05). beta
catenin localization transferred from membrane/cytoplasmic/nuclear to
cytoplasmic/nuclear, and c-Myc localization transferred from cytoplasmic/nuclear
to nuclear in both cell lines following cisplatin treatment. The rate of
apoptosis increased in a dose-dependent manner with cisplatin. After 48-h
transfection with c-myc siRNA, A549/DDP cells were blocked in the S phase, and
G0/G1-phase cells increased. Simultaneously, the apoptotic rate was increased (p
< 0.05) and the IC50 decreased significantly (p < 0.05). C-myc, the downstream
target gene of beta-catenin, plays an important role in regulating cisplatin
resistance in A549/DDP cells. C-Myc siRNA improved the sensitivity of A549/DDP
cells to cisplatin.
PMID- 25131139
TI - Effects on upper airway collapsibility of presence of a pharyngeal catheter.
AB - Catheters that traverse the pharynx are often in place during clinical or
research evaluations of upper airway function. The purpose of this study was to
determine whether the presence of such catheters affects measures of upper airway
collapsibility itself. To do so, pharyngeal critical closing pressure (Pcrit) and
resistance upstream of the site of collapse Rus) were assessed in 24 propofol
anaesthetized subjects (14 men) with and without a multi-sensor oesophageal
catheter (external diameter 2.7 mm) in place. Anaesthetic depth and posture were
maintained constant throughout each study. Six subjects had polysomnography(PSG)
defined obstructive sleep apnea (OSA) and 18 either did not have or were at low
risk of OSA. Airway patency was maintained with positive airway pressure. At
intervals, pressure was reduced by varying amounts to induce varying degrees of
inspiratory flow limitation. The slope of the pressure flow relationship for flow
limited breaths defined Rus. Pcrit was similar with the catheter in and out (-1.5
+/- 5.4 cmH2 O and -2.1 +/- 5.6 cmH2O, respectively, P = 0.14, n = 24). This
remained the case both for those with PSG-defined OSA (3.9 +/- 2.2 cmH2O and 2.6
+/- 1.4 cmH2O, n = 6) and those at low risk/without OSA (-3.3 +/- 4.9 cmH2O and
3.7 +/- 5.6 cmH2O, respectively, n = 18). Rus was similar with the catheter in
and out (20.0 +/- 12.3 cmH2O mL(-1) s(-1) and 16.8 +/- 10.1 cmH2O mL(-1) s(-1), P
= 0.22, n = 24). In conclusion, the presence of a small catheter traversing the
pharynx had no significant effect on upper airway collapsibility in these
anaesthestized subjects, providing reassurance that such measures can be made
reliably in their presence.
PMID- 25131141
TI - Is essential fatty acid status in late pregnancy predictive of post-natal
depression?
AB - OBJECTIVE: We tested the hypothesis that abnormal levels of omega-3 and omega-6
polyunsaturated fatty acids (PUFAs) during late pregnancy are associated with
antenatal and post-natal depression. METHOD: We interviewed a sample of more than
900 women in late pregnancy. We assessed whether they met criteria for depression
on a standardized measure of post-natal depression [the Edinburgh Post-natal
Depression Scale (EPDS)] and met DSM-IV criteria for major depression and/or were
in receipt of antidepressant medication. Blood was collected at that time to
generate data on nine PUFA variables. Sample members were re-interviewed post
natally to determine depressive experience in the 3 months following the birth of
their baby. RESULTS: Univariate associations were demonstrated between pre-natal
depression categorized using DSM criteria and measures of blood fatty acids
including total omega-3, the ratio of omega-6 to omega-3, docosahexaenoic acid
(DHA) omega-3 and DHA plus eicosapentaenoic acid (EPA) omega-3. Such associations
were not found post-natally, but different associations were quantified between
EPDS-diagnosed depression and total omega-6, total omega-3 and EPA omega-3. In
multivariate analyses, slight associations were maintained between EPDS and lower
omega-3, lower EPA and higher omega-6 when neuroticism, stress during pregnancy,
a lifetime episode of depression and older age were included in the analysis.
CONCLUSION: Findings in such a large sample indicate that PUFA status in late
pregnancy is only slightly linked with the risk of post-natal depression when
depression was quantified by the EPDS. There were no associations between post
natal depression diagnosed by DSM criteria and any fatty acid variables.
PMID- 25131140
TI - Targeting of viral capsids to nuclear pores in a cell-free reconstitution system.
AB - Many viruses deliver their genomes into the nucleoplasm for viral transcription
and replication. Here, we describe a novel cell-free system to elucidate specific
interactions between viruses and nuclear pore complexes (NPCs). Nuclei
reconstituted in vitro from egg extracts of Xenopus laevis, an established
biochemical system to decipher nuclear functions, were incubated with GFP-tagged
capsids of herpes simplex virus, an alphaherpesvirus replicating in the nucleus.
Capsid binding to NPCs was analyzed using fluorescence and field emission
scanning electron microscopy. Tegument-free capsids or viral capsids exposing
inner tegument proteins on their surface bound to nuclei, while capsids
inactivated by a high-salt treatment or covered by inner and outer tegument
showed less binding. There was little binding of the four different capsid types
to nuclei lacking functional NPCs. This novel approach provides a powerful system
to elucidate the molecular mechanisms that enable viral structures to engage with
NPCs. Furthermore, this assay could be expanded to identify molecular cues
triggering viral genome uncoating and nuclear import of viral genomes.
PMID- 25131142
TI - Imported loiasis in Italy: an analysis of 100 cases.
AB - BACKGROUND: loiasis is a neglected filariasis, affecting millions of individuals
living in the rainforest areas of West and Central Africa. Aim of this study was
to compare clinical and parasitological manifestations of loiasis between
subjects born in endemic areas and expatriates/travelers. METHODS: we report
clinical and parasitological manifestations of 100 patients with imported loiasis
seen between 1993 and 2013 at the Center of Tropical Diseases, Negrar, Italy.
RESULTS: among the 100 patients, 30 were African immigrants, 70 were Europeans
(59 long-term expatriates and 11 travelers). Thirty-five patients (19 Africans
and 16 Europeans) had positive microfilaremia. Calabar swellings were twice as
frequent in Europeans (90%) than in Africans (46.7%), while a history of
"eyeworm" was recorded in a higher proportion of Africans (43.3%) than in
Europeans (17.4%). The median duration of exposure in the non-endemic group was
also fairly long (14.6 years). Different drug regimens were used for treatment.
CONCLUSIONS: we suggest that the differences between Africans and Europeans are
more likely to be related to genetic differences, rather than to chronicity.
Moreover the management of imported loiasis needs standardization.
PMID- 25131143
TI - Anemia and thrombocytopenia in Plasmodium vivax malaria is not unusual in
patients from endemic and non-endemic settings.
PMID- 25131145
TI - Differential growth in estuarine and freshwater habitats indicated by plasma IGF1
concentrations and otolith chemistry in Dolly Varden Salvelinus malma.
AB - This study employed a combination of otolith microchemistry to indicate the
recent habitat use, and plasma concentrations of the hormone insulin-like growth
factor 1 (IGF1) as an index of recent growth rate, to demonstrate differences in
growth and habitat use by Dolly Varden Salvelinus malma occupying both freshwater
and estuarine habitats in south-west Alaska. Extensive sampling in all habitats
revealed that fish had higher IGF1 levels in estuarine compared to lake habitats
throughout the summer, and that the growth rates in different habitats within the
estuary varied seasonally. In addition, otolith microchemistry indicated
differentiation in estuarine habitat use among individual S. malma throughout
summer months. Although growth in the estuary was higher than in fresh water in
nearly all sites and months, the benefits and use of the estuarine habitats
varied on finer spatial scales. Therefore, this study further illustrates the
diverse life histories of S. malma and indicates an evaluation of the benefits of
marine waters needs to include sub-estuary scale habitat use.
PMID- 25131144
TI - Prospective relations between family conflict and adolescent maladjustment:
security in the family system as a mediating process.
AB - Conflict in specific family systems (e.g., interparental, parent-child) has been
implicated in the development of a host of adjustment problems in adolescence,
but little is known about the impact of family conflict involving multiple family
systems. Furthermore, questions remain about the effects of family conflict on
symptoms of specific disorders and adjustment problems and the processes
mediating these effects. The present study prospectively examines the impact of
family conflict and emotional security about the family system on adolescent
symptoms of specific disorders and adjustment problems, including the development
of symptoms of anxiety, depression, conduct problems, and peer problems. Security
in the family system was examined as a mediator of these relations. Participants
included 295 mother-father-adolescent families (149 girls) participating across
three annual time points (grades 7-9). Including auto-regressive controls for
initial levels of emotional insecurity and multiple adjustment problems (T1),
higher-order emotional insecurity about the family system (T2) mediated relations
between T1 family conflict and T3 peer problems, anxiety, and depressive
symptoms. Further analyses supported specific patterns of emotional
security/insecurity (i.e., security, disengagement, preoccupation) as mediators
between family conflict and specific domains of adolescent adjustment. Family
conflict was thus found to prospectively predict the development of symptoms of
multiple specific adjustment problems, including symptoms of depression, anxiety,
conduct problems, and peer problems, by elevating in in adolescent's emotional
insecurity about the family system. The clinical implications of these findings
are considered.
PMID- 25131146
TI - Relationships between facial temperature changes, end-exercise affect and during
exercise changes in affect: a preliminary study.
AB - The present study was performed as an evaluation of the relationships between
changes in facial temperature and self-reported pleasure-displeasure during an
acute aerobic exercise bout. Ninety-two students performed a 10-minute long
session of cycle ergometry at 80-85% of age-predicted maximal heart rate. Using
infrared thermography and a single-item measure of pleasure-displeasure (the
Feeling Scale, FS), facial temperature and the FS score were sampled at the
beginning (Min1:00) and at the end of the exercise session (Min9:00). Statistical
analyses revealed that cheek (but not forehead) temperature was higher at the end
of the exercise bout compared to Min1:00 (it increased by about 5%). Change in
cheek temperature was negatively related to end-exercise affect (beta = -0.28, P
< 0.001) and to during-exercise affective changes (beta = -0.35, P < 0.001). No
significant relationship with forehead temperature was found. Some of the
possible reasons for this differential effect as well as theoretical and
practical implications of our findings are discussed.
PMID- 25131147
TI - Revisiting the surface anatomy of the sciatic nerve in the gluteal region.
AB - The surface anatomy of the sciatic nerve (SN) in the gluteal region is clinically
important (e.g., intramuscular injection). Anatomy texts describe the nerve in
relation to the posterior superior iliac spine (PSIS), ischial tuberosity (IT),
and greater trochanter (GT) but descriptions are inconsistent. The surface
anatomy of the SN was determined in relation to these bony landmarks using
computed tomography (CT) scans in living adults. One hundred consecutive adult
pelvic CT scans (36 females, mean age 76 years) were available for dual consensus
analysis. A further 19 adults (9 females, mean age 74 years) underwent pelvic CT
scans in both prone and supine positions. The surface projection of the SN along
a line between the PSIS and IT and between the IT and GT was measured. The SN was
identified in 95% of scans at a mean of 5.2 +/- 1.0 cm from the PSIS and 11.4 +/-
1.1 cm from the IT. The SN was a mean of 5.8 +/- 0.8 cm from the IT and 6.2 +/-
1.0 cm from the GT. There were no significant differences in mean positions of
the nerve between sides and sexes. A small but clinically irrelevant difference
in the surface marking of the SN was found between supine and prone positions
with respect to the GT and IT but not in relation to the PSIS and IT. In living
adults, the SN lies approximately one-third of the way along a line between the
PSIS and IT and half way between the GT and IT.
PMID- 25131148
TI - General, but not abdominal, overweight increases odds of asthma among Norwegian
adolescents: the Young-HUNT study.
AB - AIM: The aim of this analysis was to examine the association between asthma and
general and abdominal weight status, defined by age- and sex-specific cut-offs
for body mass index (BMI) and waist circumference (WC) in adolescents. METHODS:
Participants aged 12-19 years in the Young-HUNT (YH) Study (YH1 1995-1997: n =
8222; YH3 2006-2008: n = 7403) completed self-administered questionnaires in
school as part of a series of cross-sectional, population-based studies conducted
in Nord-Trondelag, Norway. Weight, height and WC were measured. Adjusted odds
ratios (ORs) and 95% Confidence Intervals (CI) for asthma, defined by self
reported physician diagnosis, were calculated. Potential effect modifiers
evaluated included sex and pubertal development status (PDS). RESULTS: Asthma was
reported by 11.8% of the adolescents in YH1 and 17.0% in YH3. Asthma odds
significantly increased for adolescents with general (OR = 1.33; 95%CI: 1.13,
1.56), but not abdominal, overweight and increased for adolescents with general
(OR = 1.34; 95%CI: 1.02, 1.75) or abdominal obesity (OR = 1.36; 95%CI: 1.16,
1.60). Underweight had no association with asthma regardless of weight assessment
type, and PDS did not meaningfully influence the associations between asthma and
weight. CONCLUSION: Overweight and obesity both increased the odds of asthma in
12-19 year-old Norwegians. WC did not add further information to that already
provided by BMI to improve our understanding of the association between asthma
and weight.
PMID- 25131149
TI - Effects of prolonged in vitro culture and cryopreservation on viability, DNA
fragmentation, chromosome stability and ultrastructure of bovine cells from
amniotic fluid and umbilical cord.
AB - The objective of this work was to study cellular types that did not participated
in the gastrulation process, amniotic fluid cells (AFCs) and umbilical cord cells
(UCCs), in conditions of long-term culture and cryopreserved with different
solutions. The AFCs and UCCs were used in a comparative study with ear fibroblast
cells (EFCs) that were cultured in vitro until 20 cellular passages and
cryopreserved in 10% dimethylsulphoxide (DMSO), 5% dimethyl formamide (DMF) and
7% glycerol (Gly) solutions. The cellular viability, ultrastructure, DNA
fragmentation and chromosome stability were evaluated to determine the cellular
type most resistant. In all cell types, it was possible to evaluate the AFCs
until 15 passages and UCCs until 20 passages with different periods of cellular
growth to reach the confluence phase. Solutions containing 10% DMSO ensured
viability of 90.33 +/- 5.58%, 90.56 +/- 4.40% and 81.90 +/- 3.31%, respectively
for EFCs, AFCs and UCCs, being significantly more efficient and with less
variation than other cryoprotectant solutions. The AFCs were more sensitive to
cryopreservation and presented low viability rate at the passage 20 (17.2 +/-
8.87%). There was no change in karyotype and nuclear fragmentation was low in all
cellular passages studied. With the scanning electron analysis was possible the
characterization of AFCs and UCCs in suspension. The three cellular types of
cells presented different shapes and characteristics on the surface. The results
demonstrate that bovine AFCs and UCCs can be isolated, cultured in vitro and
cryopreserved in 10% DMSO, not causing damage to DNA and chromosomes. The UCCs
were more resistant than AFCs in all aspects.
PMID- 25131150
TI - Practical approach to prepare solid dispersion drug product using spherical
silicate.
AB - The purpose of this study is to establish a novel approach for preparing a solid
dispersion drug product using spherical silicate by a Wurster-type fluidized bed
granulator. The spherical silicate used in this study has porous structure and
ideal particle size for loading by a Wurster-type fluidized bed granulator. As
model drugs, ibuprofen (IBU), indomethacin (IMC), and phenytoin (PNT) were used
and the proposed approach was applied to prepare amorphous drug. All drugs could
be loaded on the spherical silicate in an amorphous state. On the other hand,
spray drying of spherical silicate suspended in IBU solution was conducted to
prepare amorphous product of IBU as a reference; however, complete amorphization
was not achieved. Dissolution profiles of each drug after loading on spherical
silicate by a Wurster-type fluidized bed granulator were evaluated, and dramatic
improvement of dissolution was observed compared with those of crystalline drug.
In the proposed approach, specific surface area and particle size of spherical
silicate were determined as a key factors to contribute to high yield of
amorphous product.
PMID- 25131151
TI - Survival dynamics of tick-borne encephalitis virus in Ixodes ricinus ticks.
AB - Biotic factors contributing to the survival of tick-borne viruses in nature are
poorly understood. Using tick-borne encephalitis virus (TBEV) and its principal
European vector, Ixodes ricinus, we examined the relative roles of salivary gland
infection, co-feeding transmission, and moulting in virus survival. Virus titres
in the salivary glands increased after blood-feeding in a time- and dose
dependent manner. This was observed in ticks infected by inoculation but not in
ticks infected by the natural route of co-feeding. Amplification of infection
prevalence occurred via co-feeding. However, when larvae or nymphs subsequently
moulted, the infection prevalence dramatically declined although this was not
observed when ticks were infected by inoculation. Trans-stadial survival is a
hitherto overlooked parameter that may contribute to the low incidence of TBEV
infection in field-collected I. ricinus ticks.
PMID- 25131153
TI - Affective neural networks and cognitive learning systems for big data analysis.
PMID- 25131152
TI - Co-circulation of multiple species of Rickettsiales bacteria in one single
species of hard ticks in Shenyang, China.
AB - Bacteria in the order Rickettsiales include some of the most important zoonotic
(re)emerging pathogens for animals and humans. In 2012, a total of 1267 adult
Haemaphysalis longicornis ticks were collected from domestic animals (cattle and
sheep) in Shenyang of Liaoning Province, China. These ticks were grouped into 181
pools (each pool with 6-7 ticks). Rickettsiales agents were identified in 93
(51.38%) tick pools using PCR targeting rrs (16S rRNA). In addition to 16S rRNA
gene sequences, gltA and groEL gene sequences were also recovered from these
positive samples. Phylogenetic analyses of these sequences revealed the presence
of five species of Rickettsiales bacteria in a single tick species (H.
longicornis) in nature in Shenyang, including Rickettsia japonica, Rickettsia
raoultii, Anaplasma centrale, Anaplasma bovis, and a potentially novel A.
phagocytophilum variant. Additionally, two Candidatus Ehrlichia spp. (Ehrlichia
sp. Yonaguni138, Candidatus Ehrlichia shimanensis) were also identified in these
ticks, with the highest prevalence of Ehrlichia sp. Yonaguni138 (73/181, 40.3%).
Notably, these agents except the novel A. phagocytophilum variant had close
evolutionary relationships with those previously identified in northeastern Asian
countries including Korea, Japan, and Russia, indicating a geographic clustering
pattern. Our data also reinforce the need for vigilance in recognition and
prevention of rickettsiosis, ehrlichiosis, and anaplasmosis in humans and animals
in this region.
PMID- 25131154
TI - Perspectives on heterogeneous photochemistry.
AB - Heterogeneous photochemistry has a potentially important role in production of
energy, in environmental remediation and in sustainable production of chemicals.
Photochemical efficiency depends on both materials properties and the desired
chemical reaction that is promoted through creation of an excited state. A
detailed understanding of the interplay between materials properties and
reactivity requires a molecular-scale approach that determines the elementary
steps in the overall process. This personal account summarizes the role of
defects in determining the photochemical and thermal reactions on rutile titania,
a model for semiconductor metal oxide photocatalysts that defects, e.g., Ti
interstitials present in the subsurface region, and O adatoms on the surface,
have a substantial impact on the efficiency for photochemical conversion through
modification of molecular binding and also through likely modification of charge
carrier dynamics. Design of materials must include engineering of the optical and
electronic properties of the semiconductor photocatalyst, and understanding of
the key photochemical steps involved in specific processes to ensure proper
alignment of their electronic states with the band structure of the material.
Thus, fundamental surface science studies and development of time-dependent
theoretical methods that map out the reaction mechanism for photochemical
processes on materials with controlled composition and structure are critical.
PMID- 25131155
TI - Leptin receptor is expressed by epidermis and skin appendages in dog.
AB - Leptin is a polypeptide secreted by adipocytes which binds to a specific receptor
(Ob-R) that is expressed in various tissues. The wide distribution of the Ob-R
suggests that leptin might exert diverse biological functions, not only by
regulating energy metabolism and appetite, but also by acting as a mitogen in
many cell types, including keratinocytes. In this study, the presence and
localization of Ob-R was investigated in the skin of the dog using RT-PCR and
immunohistochemical techniques. RT-PCR revealed the presence of Ob-R m-RNA in the
skin specimens collected from the dorsal region of two smooth coat breed dogs.
Through immunohistochemistry performed on the skin of five dogs, the expression
of the receptor was observed in the basal layer of the epidermis, in the hair
follicles as well as in the apocrine sweat and sebaceous glands. No staining for
Ob-R was detected in the suprabasal epidermis layers. Strong positive signals
were observed in many cells of the outer root sheath of hair follicles in growing
and in regressive phases. The identification of Ob-R in the above targets
suggests that leptin may play a role in the regulation of cyclic renewal of the
epidermis and skin appendages in dog. This study represents an important
contribution to understand the complex mechanisms that are involved in the skin
biology in this species.
PMID- 25131157
TI - Impact of Body Mass Index on Progression of IgA Nephropathy Among Japanese
Patients.
AB - BACKGROUND: The impact of being overweight remains unclear in Asian populations
that tend to be lean. The objective of this study is to clarify the impact of
body mass index (BMI) and metabolic factors on the prognosis of Japanese patients
with IgA nephropathy (IgAN). METHODS: A total of 193 patients with IgAN were
divided into three groups equally according to BMI: Group L (lean group, BMI:
15.6-20.1 kg/m(2) ), Group M (middle group, BMI: 20.2-23.0 kg/m(2) ), and Group O
(obesity group, BMI: 23.1-31.9 kg/m(2) ). Clinical data at the time of renal
biopsy and the progression of the patients after renal biopsy were analyzed.
RESULTS: At the time of renal biopsy, hypertension, dyslipidemia, hyperuricemia,
and hypercomplementemia in Group O were more significant compared with those in
Group L and/or Group M. Uric acid, triglyceride, C3, C4, high-density lipoprotein
cholesterol, serum creatinine, systolic blood pressure (BP), and diastolic BP
were significantly correlated with BMI. In Group O, the remission of urinary
protein over 5 years was significantly delayed using a log-rank test. At the
final observation, the BMI of each group was as similar as that at renal biopsy.
The patients with aggressive therapy, such as steroid therapy and/or
tonsillectomy in Group O did not have major side effects, except for a slight
elevation of total cholesterol and low-density lipoprotein cholesterol.
CONCLUSION: Even slightly high BMI seems to be a risk factor for progress in
Japanese patients with IgAN.
PMID- 25131158
TI - Precise determination of the threshold diameter for a single-walled carbon
nanotube to collapse.
AB - Closed-edged bilayer graphene nanoribbons were formed by the spontaneous collapse
of large-diameter single-walled carbon nanotubes (SWNTs) grown on gold
nanoparticles by chemical vapor deposition. Such bilayer graphene nanoribbons
could adopt different stacking configurations, such as AB-stacking or stacking
order with any rotation angle, correlated with the chiral angles of their parent
rounded SWNTs. On the basis of the electron diffraction characterizations on a
good number of collapsed and uncollapsed SWNTs, the threshold diameter for SWNTs
to collapse was precisely determined to be 5.1 nm, independent of the chiral
angle of the SWNTs. The determination is consistent with that calculated by both
classical adaptive intermolecular reactive empirical bond order force field and
density functional theory after having taken the stacking effect and thermal
fluctuation into account.
PMID- 25131156
TI - Impact of a pharmacy benefit change on new use of mail order pharmacy among
diabetes patients: the Diabetes Study of Northern California (DISTANCE).
AB - OBJECTIVE: To assess the impact of a pharmacy benefit change on mail order
pharmacy (MOP) uptake. DATA SOURCES/STUDY SETTING: Race-stratified, random sample
of diabetes patients in an integrated health care delivery system. STUDY DESIGN:
In this natural experiment, we studied the impact of a pharmacy benefit change
that conditionally discounted medications if patients used MOP and prepaid two
copayments. We compared MOP uptake among those exposed to the benefit change (n =
2,442) and the reference group with no benefit change (n = 8,148), and estimated
differential MOP uptake across social strata using a difference-in-differences
framework. DATA COLLECTION/EXTRACTION METHODS: Ascertained MOP uptake (initiation
among previous nonusers). PRINCIPAL FINDINGS: Thirty percent of patients started
using MOP after receiving the benefit change versus 9 percent uptake among the
reference group (p < .0001). After adjustment, there was a 26 percentage point
greater MOP uptake (benefit change effect). This benefit change effect was
significantly smaller among patients with inadequate health literacy (15 percent
less), limited English proficiency (14 percent less), and among Latinos and
Asians (24 and 16 percent less compared to Caucasians). CONCLUSIONS:
Conditionally discounting medications delivered by MOP effectively stimulated MOP
uptake overall, but it unintentionally widened previously existing social gaps in
MOP use because it stimulated less MOP uptake in vulnerable populations.
PMID- 25131159
TI - Modification of a melanoma discrimination index derived from hyperspectral data:
a clinical trial conducted in 2 centers between March 2011 and December 2013.
AB - BACKGROUND: The morphology of pigmented skin lesions (PSLs) is predominantly a
result of varying concentrations and distributions of pigmented molecules such as
melanin and hemoglobin. Based on these differences and the fact that their
information is contained in cutaneous spectra, a hyperspectral imager (HSI) for
pigmented melanoma and a single discrimination index derived from the resultant
hyperspectral data are proposed. OBJECTIVE: To develop and evaluate a new
discrimination index for melanomas, compared to the previous index. METHODS: A
HSI, which is convenient for both patients and clinicians, was newly developed
and used in a clinical trial conducted in 2 centers with 80 patients with primary
lesions and 17 volunteers between March 2011 and December 2013. There were 24
melanomas and 110 other PSLs. A previously proposed discrimination index was used
without modifications. A new index, which emphasized the essential features of
melanoma, was proposed, and its performance was examined. For each index, a
threshold value was set to minimize the average value of the false positive and
false negative fractions. The performances of both indices were compared.
RESULTS: The sensitivity and specificity of the old index were 75% and 97%,
respectively, while those of the new index were 96% and 87%. CONCLUSION: The new
index had a higher sensitivity and adequate specificity, indicating that it is
more useful than the old index.
PMID- 25131160
TI - The immune pathogenesis of immune reconstitution inflammatory syndrome associated
with highly active antiretroviral therapy in AIDS.
AB - The present study investigated the immunological pathogenesis of immune
reconstitution inflammatory syndrome (IRIS) in acquired immunodeficiency syndrome
(AIDS) patients undergoing highly active antiretroviral therapy (HAART). A total
of 238 patients with AIDS who received initial HAART were included in this
prospective cohort study. Blood samples were collected immediately, at baseline,
at week 12, and at week 24 after initial HAART and at the onset of IRIS.
Lymphocyte subsets, Th1 and Th2 cytokines, and interleukin (IL)-7 levels were
measured by flow cytometry or ELISA. Among the 238 patients with AIDS who
received HAART, 47 patients developed IRIS. The percentages of CD4(+) and CD8(+)
naive, memory, and activated cells exhibited no significant differences between
AIDS patients with and without IRIS 24 weeks after initial HAART. The percentage
of CD4(+)CD25(+)Foxp3(+) regulatory T cells was lower in IRIS patients than in
non-IRIS patients before HAART, 12 weeks after HAART, 24 weeks after HAART, and
at the onset of IRIS. IL-2 and interferon (IFN)-gamma levels were significantly
higher at week 4 and at the onset of IRIS in IRIS patients than in non-IRIS
patients. In contrast, IL-4 and IL-10 levels were significantly lower at week 4
and at the onset of IRIS in IRIS patients than in non-IRIS patients. Plasma IL-7
decreased gradually with the progression of HAART. The level of IL-7 was higher
in IRIS patients than in non-IRIS patients at all follow-up time points. An
imbalance of Th1/Th2 cytokines, a consistently low CD(+)CD25(+)Fox3(+)
percentage, and a high IL-7 level may be crucial in the pathogenesis of IRIS in
AIDS patients who had received HAART.
PMID- 25131161
TI - Psychogenic nonepileptic seizures: should we use response to AEDS as a red flag
for the diagnosis?
AB - PURPOSE: Lack of response to anti-epileptic drugs (AEDS) is considered a "red
flag" pointing to a diagnosis of Psychogenic Nonepileptic Seizures (PNES). On the
other hand, placebo effects are relevant in any medical condition with a complex
psychosocial component. We aimed to evaluate the presence and frequency of a
placebo response in patients with sole PNES and explore its impact on diagnostic
delay. METHODS: We reviewed the medical records of 102 patients referred for
video EEG monitoring and diagnosed with PNES. Patients with PNES and epilepsy
were excluded. The response to AEDs was analyzed according to patients' reports
and medical records. Patients were classified, according to the response to AEDs,
in two groups: responders (patients achieving remission) and non-responders.
Then, we compared the diagnostic delay from the first event to the final
diagnosis between these groups. RESULTS: Forty-seven patients (79.7%) with sole
PNES who were using AEDs were identified. Twenty-two patients (46.8%) had
reported complete or partial remission of PNES with mean response duration of 7.2
months (SD+9.6 months). The time delay of the diagnosis in the AED responder
group was 10.6 years; the delay in non-responders was 5.6 years (p=0.035).
CONCLUSION: Patients with sole PNES receiving AEDs can go into PNES remission. A
favorable response to AEDs is likely to be interpreted as supporting a diagnosis
of epilepsy and is associated with diagnostic delay. Physicians should bear in
mind that patients with PNES may be particularly vulnerable to placebo effects.
PMID- 25131162
TI - Ehlers-Danlos syndrome: a cause of epilepsy and periventricular heterotopia.
AB - PURPOSE: Ehlers-Danlos syndrome (EDS) comprises a variety of inherited connective
tissue disorders that have been described in association with various
neurological features. Until now the neurological symptoms have not been studied
in detail; therefore, the aim of this review is to analyze the possible
association between EDS, epilepsy and periventricular heterotopia (PH). METHODS:
We have carried out a critical review of all cases of epilepsy in EDS patients
with and without PH. RESULTS: Epilepsy is a frequent neurological manifestation
of EDS; generally, it is characterized by focal seizures with temporo-parieto
occipital auras and the most common EEG findings epileptiform discharges and slow
intermittent rhythm with delta-theta waves. Epilepsy in EDS patients is usually
responsive to common antiepileptic therapy; very few cases of drug resistant
focal epilepsy requested surgical treatment, with favorable results in terms of
outcome. Epilepsy is the most common presenting neurological manifestation
associated with PH in EDS patients. Abnormal anatomic circuitries (including
heterotopic nodules) could generate epilepsy in patients with PH. CONCLUSION:
Among the principal neurological manifestations, epilepsy and PH have a
considerable importance and can influence the long-term evolution of these
patients. We hypothesize that PH may determine the epileptic manifestations in
patients with EDS; much remains to be learnt about the relationships between
nodules and the epileptic manifestations in EDS syndrome.
PMID- 25131163
TI - Human Beta-papillomavirus infection and keratinocyte carcinomas.
AB - Although the role of oncogenic human Alpha-papillomaviruses (HPVs) in the
development of mucosal carcinomas at different body sites (eg cervix, anus,
oropharynx) is fully recognized, a role for HPV in keratinocyte carcinomas (KCs;
basal and squamous cell carcinomas) of the skin is not yet clear. KCs are the
most common cancers in Caucasians, with the major risk factor being ultraviolet
(UV) light exposure. A possible role for Beta-HPV types (BetaPV) in the
development of KC was suggested several decades ago, supported by a number of
epidemiological studies. Our current review summarizes the recent molecular and
histopathological evidence in support of a causal association between BetaPV and
the development of KC, and outlines the suspected synergistic effect of viral
gene expression with UV radiation and immune suppression. Further insights into
the molecular pathways and protein interactions used by BetaPV and the host cell
is likely to extend our understanding of the role of BetaPV in KC.
PMID- 25131164
TI - Pharmacokinetics of oral chlortetracycline in nonpregnant adult ewes.
AB - The objectives of this study were to determine plasma concentrations and
pharmacokinetic parameters of feed-grade chlortetracycline (CTC) in sheep after
oral administration of 80 or 500 mg/head daily, divided into two equal doses
given at 12-h intervals for 8 days. These are the approved, and commonly used but
unapproved, feed additive doses, respectively, in the United States for the
prevention of ovine infectious abortion. Blood samples were collected just prior
to dosing at 0, 12, 24, 72, 96, and 192 h, as well as 4, 8, 12, 24, and 36 h
after the last dose, and noncompartmental pharmacokinetic analysis was performed
to estimate elimination half-life and area under the plasma concentration-time
curve (AUC). Mean observed maximum CTC concentrations (Cmax ) were 20.0 ng/mL (80
mg dose) and 101 ng/mL (500 mg dose). Mean apparent elimination half-life was 18
h (80 mg dose) and 20 h (500 mg dose). Although published data do not exist to
estimate plasma CTC concentrations necessary for the prevention of ovine
infectious abortion, concentrations reached in our study suggest that either the
FDA-approved and FDA-unapproved dosages are not high enough or that the
pharmacodynamic parameter relating preventive dose to pathogen minimum inhibitory
concentrations is yet to be determined.
PMID- 25131166
TI - Transcatheter implantation of a newly designed aortic prosthesis in a patient
with a mechanical mitral valve.
PMID- 25131165
TI - Total arterial revascularization with internal thoracic and radial artery grafts
in triple-vessel coronary artery disease is associated with improved survival.
AB - OBJECTIVES: We sought to evaluate our experience with total arterial
revascularization and compare it with the traditional approach of a single
internal thoracic artery supplemented by saphenous veins. METHODS: From 1995 to
2010, 6059 patients with triple-vessel coronary artery disease underwent primary
isolated coronary artery bypass grafting at 8 centers. A study cohort of 3774
patients was formed, with 2988 (79%) undergoing total arterial revascularization
and 786 (21%) receiving only saphenous veins to supplement a single in situ
internal thoracic artery. In the total arterial revascularization group,
bilateral internal thoracic arteries were used in 1079 patients (36%) and at
least 1 radial artery was used in 2916 patients (97%). Propensity score matching
was used for risk adjustment. RESULTS: Patients undergoing total arterial
revascularization were younger (65.0+/-10.4 years vs 71.3+/-7.9 years, P<.001)
and less likely to have diabetes, cerebrovascular disease, recent myocardial
infarction, and severe left ventricular impairment. At 15 years, patients who
underwent total arterial revascularization experienced superior unadjusted
survival (62%+/-1.1% vs 35%+/-1.9%, P<.001). Multivariable Cox regression in the
entire study cohort showed the total arterial group had improved survival with a
hazard ratio of 0.79 (95% confidence interval, 0.70-0.90; P<.001). After
propensity score matching yielded 384 patient pairs, patients who underwent total
arterial revascularization showed improved survival at 15 years than patients who
underwent single arterial revascularization (54%+/-3.3% vs 41%+/-3.0%, P=.0004).
CONCLUSIONS: This large multicenter study suggests that a strategy of total
arterial revascularization is associated with improved long-term survival
compared with the use of only a single arterial and saphenous vein grafts. Total
arterial revascularization should be encouraged in patients with a reasonable
life expectancy.
PMID- 25131167
TI - Usefulness of bridging thoracic endovascular aortic repair and sac irrigation
followed by open repair in patients with mycotic thoracic aortic aneurysms.
PMID- 25131168
TI - Skeletal muscle and plasma concentrations of cefazolin during cardiac surgery in
infants.
AB - OBJECTIVE: To describe the pharmacokinetics and tissue disposition of
prophylactic cefazolin into skeletal muscle in a pediatric population undergoing
cardiac surgery. METHODS: The subjects included 12 children, with a median age of
146 days (interquartile range, 136-174) and median weight of 5.5 kg
(interquartile range, 5.2-7.3) undergoing cardiac surgery and requiring
cardiopulmonary bypass with or without deep hypothermic circulatory arrest.
Institutional cefazolin at standard doses of 25 mg/kg before incision and 25
mg/kg in the bypass prime solution were administered. Serial plasma and skeletal
muscle microdialysis samples were obtained intraoperatively and the unbound
cefazolin concentrations measured. Noncompartmental pharmacokinetic analyses were
performed and the tissue disposition evaluated. RESULTS: After the first dose of
cefazolin, the skeletal muscle concentrations peaked at a median microdialysis
collection interval of 30 to 38.5 minutes. After the second dose, the peak
concentrations were delayed a median of 94 minutes in subjects undergoing deep
hypothermic circulatory arrest. Skeletal muscle exposure to cefazolin measured by
the area under concentration time curve 0-last measurement was less in the
subjects who underwent deep hypothermic circulatory arrest than in those who
received cardiopulmonary bypass alone (P = .04). The skeletal muscle
concentrations of cefazolin exceeded the goal concentrations for methicillin
sensitive Staphylococcus aureus prophylaxis; however, the goal concentrations for
gram-negative pathogens associated with surgical site infections were achieved
only 42.1% to 84.2% and 0% to 11.2% of the intraoperative time in subjects
undergoing cardiopulmonary bypass alone or deep hypothermic circulatory arrest,
respectively. CONCLUSIONS: This cefazolin dosing strategy resulted in skeletal
muscle concentrations that are likely not effective for surgical prophylaxis
against gram-negative pathogens but are effective against methicillin-sensitive S
aureus in infants undergoing cardiac surgery.
PMID- 25131169
TI - The CarboMedics supra-annular Top Hat valve improves long-term left ventricular
mass regression.
AB - OBJECTIVE: The present study aimed to identify potential differences in
hemodynamic performance between the supra-annular CarboMedics Top Hat valve and
the intra-annular CarboMedics standard valve in terms of the long-term left
ventricular mass reduction and transvalvular gradients. METHODS: We
retrospectively reviewed a series of 186 consecutive patients who had undergone
aortic valve replacement with a small size mechanical prosthesis at our
institution from 2003 to 2013, receiving either a CarboMedics Top Hat valve (53
patients, valve size, 21 mm in 52.8% and 23 mm in 47.2%) or a CarboMedics
standard prosthesis (133 patients, valve size, 19 mm in 14.3% and 21 mm in
85.7%). RESULTS: The in-hospital mortality was 9.4% and 11.3% in the Top Hat and
standard groups, respectively (P = .71). The mean percentage of left ventricular
mass reduction was greater in the Top Hat group (33% +/- 15.8% vs 20.1% +/-
16.6%, P < .001). The mean postoperative peak aortic gradient was lower in the
Top Hat group (19.9 +/- 8.9 vs 29.6 +/- 8.6 mm Hg; P < .001). Spearman analysis
showed a positive correlation between the indexed effective orifice area and the
percentage of left ventricular mass reduction (Rho = +0.65, P = .02). The
survival in the Top Hat group was 79.7% and 71.7% at 5 and 10 years,
respectively. In the standard group, survival was 66.8% and 61.5% at 5 and 10
years, respectively (log-rank test, 0.19). Cox regression demonstrated severe
myocardial hypertrophy (hazard ratio, 2.559; 95% confidence interval, 1.095
5.981) as one of the independent predictors of survival. CONCLUSIONS: The Top Hat
valve surpasses hemodynamically the intra-annular valve. We suggest the supra
annular Top Hat prosthesis can be especially recommended for patients with a
small aortic root and severe myocardial hypertrophy.
PMID- 25131171
TI - A simple approach to mitral valve repair: posterior leaflet height adjustment
using a partial fold of the free edge.
AB - OBJECTIVES: Multiple techniques have been used to repair degenerative mitral
valve prolapse with leaflet elongation, without creating systolic anterior
motion. We describe a simple, reproducible, measured technique to guide repair.
METHODS: From January 2010 to July 2012, 171 patients underwent mitral valve
repair; 128 (75%) with Carpentier type II prolapse. For 48 patients (37.5%), the
resected posterior leaflet free edge was partially folded to restore the normal
2:1 ratio of the A2 and P2. All patients underwent complete ring annuloplasty
sized to the height of A2. RESULTS: The preoperative A2/P2 ratio was 1.5 +/- 0.5.
After repair, the A2/P2 ratio was 1.9 +/- 0.3 and 2.0 +/- 0.3 in the no fold and
partial fold groups, respectively (P = .57). The ring sizes were larger in the
partial fold group (P < .001) because the A2 height was larger (P = .001). No
obstructive systolic anterior motion was present. Of the 171 patients, 91.4% had
grade 4+ preoperative mitral regurgitation, with no 3 or 4+ mitral regurgitation
during follow-up. At the last follow-up visit, grade 2+ mitral regurgitation was
observed in 5% of the patients. No 30-day mortalities or reoperations occurred.
CONCLUSIONS: Partial fold of the posterior leaflet free edge is a simple
technique to restore the normal 2:1 ratio of A2/P2 with a ring size determined by
the A2 height. Using just the A2 height, mitral surgeons can reproducibly repair
the posterior leaflet prolapse, choose the appropriate ring size, and avoid more
complex leaflet reconstruction or judgment of the neochord length.
PMID- 25131172
TI - New technique for passage of endograft through problematic arch anatomy.
PMID- 25131173
TI - Expanded level of sympathetic chain removal does not increase the incidence or
severity of compensatory hyperhidrosis after endoscopic thoracic sympathectomy.
AB - OBJECTIVE: Compensatory hyperhidrosis is a common devastating adverse effect
after endoscopic thoracic sympathectomy for patients undergoing surgical
treatment of primary hyperhidrosis. We sought to determine whether a correlation
existed in our patient population between the level and extent of sympathetic
chain resection and the subsequent development of compensatory hyperhidrosis.
METHODS: All patients undergoing endoscopic thoracic sympathectomy in the T2-T3,
T2-T4, T2-T5, or T2-T6 levels for palmar or axillary hyperhidrosis at the
University of Iowa Hospital and Clinics (n = 97) from January 2004 to January
2013 were retrospectively reviewed. RESULTS: Differences in the preoperative
patient characteristics were not statistically significant among the patients
receiving T2-T3, T2-T4, T2-T5, or T2-T6 level resections. Of the 97 included
patients, 28 (29%) experienced transient compensatory hyperhidrosis and 4 (4%)
complained of severe compensatory hyperhidrosis and required additional
treatment. No operative mortalities occurred, and the morbidity was similar among
the groups. CONCLUSIONS: Most patients had successful outcomes after undergoing
extensive resection without changes in the incidence of compensatory
hyperhidrosis. Therefore, we recommend performing complete and adequate resection
for relief of symptoms in patients with primary hyperhidrosis.
PMID- 25131174
TI - Surgical repair of descending thoracic and thoracoabdominal aortic aneurysm
involving the distal arch: open proximal anastomosis under deep hypothermia
versus arch clamping technique.
AB - BACKGROUND: Surgical repair of a descending thoracic and thoracoabdominal aortic
aneurysm (DTA/TAAA) involving the distal arch is challenging and requires either
deep hypothermic circulatory arrest (DHCA) or crossclamping of the distal arch.
The aim of this study was to compare these 2 techniques in the treatment of
DTA/TAAA involving the distal arch. METHODS: From 1994 to 2012, 298 patients
underwent open repair of DTA/TAAA through a left thoracotomy. One hundred seventy
four patients with distal arch involvement who were suitable for either DHCA
(n=81) or arch clamping (AC; n=93), were analyzed. In-hospital outcomes were
compared using propensity scores and inverse-probability-of-treatment weighting
adjustment to reduce treatment selection bias. RESULTS: Early mortality was 11.1%
in the DHCA group and 8.6% in the AC group (P=.58). Major adverse outcomes
included stroke in 16 patients (9.2%), low cardiac output syndrome in 15 (8.6%),
paraplegia in 10 (5.7%), and multiorgan failure in 10 (5.7%). After adjustment,
patients who underwent DHCA were at similar risk of death (odds ratio [OR], 1.14;
P=.80) and permanent neurologic injury (OR, 0.95; P=.92) to those who underwent
AC. Although prolonged ventilator support (>24 hours) was more frequent with DHCA
than with AC (OR, 2.60; P=.003), DHCA showed a tendency to lower the risk of
paraplegia (OR, 0.15; P=.057). CONCLUSIONS: Compared with AC, DHCA did not
increase postoperative mortality and morbidity, except for prolonged ventilator
support. However, DHCA may offer superior spinal cord protection to AC during
repair of DTA/TAAA involving the distal arch.
PMID- 25131175
TI - Echo-acoustic flow dynamically modifies the cortical map of target range in bats.
AB - Echolocating bats use the delay between their sonar emissions and the reflected
echoes to measure target range, a crucial parameter for avoiding collisions or
capturing prey. In many bat species, target range is represented as an orderly
organized map of echo delay in the auditory cortex. Here we show that the map of
target range in bats is dynamically modified by the continuously changing flow of
acoustic information perceived during flight ('echo-acoustic flow'). Combining
dynamic acoustic stimulation in virtual space with extracellular recordings, we
found that neurons in the auditory cortex of the bat Phyllostomus discolor encode
echo-acoustic flow information on the geometric relation between targets and the
bat's flight trajectory, rather than echo delay per se. Specifically, the
cortical representation of close-range targets is enlarged when the lateral
passing distance of the target decreases. This flow-dependent enlargement of
target representation may trigger adaptive behaviours such as vocal control or
flight manoeuvres.
PMID- 25131176
TI - A new target for the old regulator: H-NS suppress T6SS secretory protein EvpP,
the major virulence factor in the fish pathogen Edwardsiella tarda.
AB - The evpP gene in fish pathogen Edwardsiella tarda, coding the T6SS secretory
protein EvpP and carrying an evpA-evpO independent promoter region, was crucial
for host cell invasion. The transcription of evpP was positively regulated by
either the two-component system EsrA-EsrB or iron concentration, and its
overexpression was known to enhance the invasion ability in our previous study.
This work demonstrated that the H-NS protein, a pleiotropic regulator of gene
expression, was a new transcriptional modulator of evpP gene. The results showed
that in vivo the transcriptional level of evpP was downregulated by H-NS and in
vitro this global regulator interacted directly with evpP promoter region.
Moreover, DNase I footprinting experiments mapping the interaction regions of H
NS and evpP revealed that this global regulator bound to evpP promoter and
neighbouring areas at multiple sites. We provided a new insight into evpP
regulation network and demonstrated the repression of H-NS to the transcription
of evpP gene. SIGNIFICANCE AND IMPACT OF THE STUDY: Recently, the devastating
fish disease edwardsiellosis caused by Edwardsiella tarda has been widely
concerned. The xenogeneic silencing of the classic regulator H-NS to the T6SS
secretory protein EvpP, which played an important role in the virulence of Edw.
tarda, was firstly reported in this study. It raised a better understanding of
the virulence regulation of EvpP and provided more information about the complex
infection mechanism of this pathogen. Our findings would contribute to the
development of live attenuated vaccines against edwardsiellosis thus reducing the
economic losses caused by this bacterium.
PMID- 25131178
TI - Edge effects on moisture reduce wood decomposition rate in a temperate forest.
AB - Forests around the world are increasingly fragmented, and edge effects on forest
microclimates have the potential to affect ecosystem functions such as carbon and
nutrient cycling. Edges tend to be drier and warmer due to the effects of
insolation, wind, and evapotranspiration and these gradients can penetrate
hundreds of metres into the forest. Litter decomposition is a key component of
the carbon cycle, which is largely controlled by saprotrophic fungi that respond
to variation in temperature and moisture. However, the impact of forest
fragmentation on litter decay is poorly understood. Here, we investigate edge
effects on the decay of wood in a temperate forest using an experimental
approach, whereby mass loss in wood blocks placed along 100 m transects from the
forest edge to core was monitored over 2 years. Decomposition rate increased with
distance from the edge, and was correlated with increasing humidity and moisture
content of the decaying wood, such that the decay constant at 100 m was nearly
twice that at the edge. Mean air temperature decreased slightly with distance
from the edge. The variation in decay constant due to edge effects was larger
than that expected from any reasonable estimates of climatic variation, based on
a published regional model. We modelled the influence of edge effects on the
decay constant at the landscape scale using functions for forest area within
different distances from edge across the UK. We found that taking edge effects
into account would decrease the decay rate by nearly one quarter, compared with
estimates that assumed no edge effect.
PMID- 25131179
TI - The consequences of contracting early and often.
PMID- 25131177
TI - Quantification of in vivo colonic motor patterns in healthy humans before and
after a meal revealed by high-resolution fiber-optic manometry.
AB - BACKGROUND: Until recently, investigations of the normal patterns of motility of
the healthy human colon have been limited by the resolution of in vivo recording
techniques. METHODS: We have used a new, high-resolution fiber-optic manometry
system (72 sensors at 1-cm intervals) to record motor activity from colon in 10
healthy human subjects. KEY RESULTS: In the fasted colon, on the basis of rate
and extent of propagation, four types of propagating motor pattern could be
identified: (i) cyclic motor patterns (at 2-6/min); (ii) short single motor
patterns; (iii) long single motor patterns; and (iv) occasional retrograde, slow
motor patterns. For the most part, the cyclic and short single motor patterns
propagated in a retrograde direction. Following a 700 kCal meal, a fifth motor
pattern appeared; high-amplitude propagating sequences (HAPS) and there was large
increase in retrograde cyclic motor patterns (5.6 +/- 5.4/2 h vs 34.7 + 19.8/2 h;
p < 0.001). The duration and amplitude of individual pressure events were
significantly correlated. Discriminant and multivariate analysis of duration,
gradient, and amplitude of the pressure events that made up propagating motor
patterns distinguished clearly two types of pressure events: those belonging to
HAPS and those belonging to all other propagating motor patterns. CONCLUSIONS &
INFERENCES: This work provides the first comprehensive description of colonic
motor patterns recorded by high-resolution manometry and demonstrates an
abundance of retrograde propagating motor patterns. The propagating motor
patterns appear to be generated by two independent sources, potentially
indicating their neurogenic or myogenic origin.
PMID- 25131180
TI - Delayed QRS transition in the precordial leads of an electrocardiogram as a
predictor of sudden cardiac death in the general population.
AB - BACKGROUND: QRS transition zone is related to the electrical axis of the heart in
the horizontal plane and is easily determined from the precordial leads of a
standard 12-lead ECG. However, whether delayed QRS transition, or clockwise
rotation of the heart, carries prognostic implications and predicts sudden
cardiac death (SCD) is unclear. OBJECTIVE: The purpose of this study was to study
whether delayed transition is associated with mortality and SCD. METHODS: We
evaluated 12-lead ECGs of 10,815 Finnish middle-aged subjects from the general
population (52% men, mean age 44 +/- 8.5 years) and followed them for 30 +/- 11
years. Main end-points were mortality and SCD. RESULTS: Delayed QRS transition at
lead V4 or later occurred in 1770 subjects (16.4%) and markedly delayed
transition at lead V5 or later in 146 subjects (1.3%). Delayed transition zone
was associated with older age, male gender, higher body mass index, hypertension,
baseline cardiovascular disease, leftward shift of the frontal QRS axis, wider
QRS-T angle, and ECG left ventricular hypertrophy. After adjusting for several
clinical and ECG variables, delayed transition was associated with overall
mortality (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.07-1.22, P <
.001) and SCD (HR 1.23, 95% CI 1.03-1.47, P = .029). Markedly delayed transition
at V5 or later predicted significantly SCD (HR 1.89, 95% CI 1.18-3.03, P = .008)
and all-cause mortality (HR 1.30, 95% CI 1.07-1.58, P = .01). However, further
adjustments for repolarization abnormalities attenuated this effect. CONCLUSION:
Delayed QRS transition in the precordial leads of an ECG seems to be a novel ECG
risk marker for SCD. In particular, markedly delayed transition was associated
with significantly increased risk of SCD, independent of confounding factors.
PMID- 25131181
TI - [Familial combined hyperlipidemia: consensus document].
AB - Familial combined hyperlipidemia (FCH) is a frequent disorder associated with
premature coronary artery disease. It is transmitted in an autosomal dominant
manner, although there is not a unique gene involved. The diagnosis is performed
using clinical criteria, and variability in lipid phenotype and family history of
hyperlipidemia are necessaries. Frequently, the disorder is associated with type2
diabetes mellitus, arterial hypertension and central obesity. Patients with FCH
are considered as high cardiovascular risk and the lipid target is an LDL
cholesterol <100mg/dL, and <70mg/dL if cardiovascular disease or type 2 diabetes
are present. Patients with FCH require lipid lowering treatment using potent
statins and sometimes, combined lipid-lowering treatment. Identification and
management of other cardiovascular risk factors as type 2 diabetes and
hypertension are fundamental to reduce cardiovascular disease burden. This
document gives recommendations for the diagnosis and global treatment of patients
with FCH directed to specialists and general practitioners.
PMID- 25131182
TI - Myelosuppression toxicity of palliative splenic irradiation in myelofibrosis and
malignant lymphoma.
AB - OBJECTIVES: Distinctive splenomegaly resulting from extramedullary hematopoiesis
and infiltration of neoplastic cells is observed in some patients with
myelofibrosis (MF) or malignant lymphoma. Palliative splenic irradiation is known
to be effective for such patients and is widely performed. However, little is
known about the biological mechanism of palliative splenic irradiation. Various
reports have focused on irradiation doses, in terms of efficacy and safety. We
examined the toxicity of myelosuppression and the timing of the platelet, white
blood cell, and red blood cell count nadirs within 3 months after the start of
irradiation in a total of eight patients with MF or malignant lymphoma, all of
whom underwent palliative splenic irradiation at our hospital between 2004 and
2013. METHODS: Five patients with idiopathic MF and three patients with non
Hodgkin's lymphoma (NHL) treated with splenic irradiation between 2004 and 2013.
Of the three patients with NHL, two had diffuse large B-cell lymphoma and one had
mantle cell lymphoma. There were four male and four female patients, with median
age of 61 years (range, 51-73). Patients with MF received irradiation at 20-100
cGy per fraction dose; four patients received irradiation five times a week and
one patient received irradiation three times a week. In three of these patients,
the irradiation dose was gradually increased while observing for hematotoxicity.
Patients with NHL received irradiation at a fraction dose of 150-200 cGy, and all
received irradiation five times a week. Irradiation was terminated when we judged
symptoms to be alleviated, splenomegaly reduced, or efficacy to be poor. With
regard to the total irradiation dose, 175, 320, 400, 600, and 640 cGy were given
to one MF patient each, and 1050 and 3000 cGy were given to one and two NHL
patients, respectively. RESULTS: Symptoms diminished or disappeared in five of
the six symptomatic patients (83%). A reduction in the size of the spleen was
confirmed in five of six patients (83%) with splenomegaly. For MF, the platelet
count nadir was observed at week 3 in two patients, week 5 in two, and week 6 in
one patient. For NHL, it was observed at week 1 in one patient, week 4 in one,
and week 9 in one patient. For MF, the white blood cell count nadir was observed
in at week 2 in one patient, week 3 in two, and week 5 in two patients. For NHL,
it was observed at week 1 in one patient and week 4 in two patients. For MF, the
red blood cell count nadir was observed at week 1 in two patients, week 3 in one,
week 7 in one, and week 8 in one patient. For NHL patients, it was observed at
week 1 in one patient, week 4 in one, and week 9 in one patient. Discussion There
was a trend for the nadir to be steeper in patients with MF than in those with
NHL. With regard to the total dose, symptoms diminished at the minimum dose of
175 cGy in MF patients, whereas the maximum dose of 3000 cGy was not effective in
NHL patients. These observations suggest that a splenic lesion in NHL patients
may be the primary site of neoplastic cell infiltration and that extramedullary
hematopoiesis may not necessarily occur in the spleen. CONCLUSION: Although
palliative irradiation of splenic lesions in patients with MF or NHL is safe and
effective, optimal irradiation doses may differ for MF and NHL. More cases need
to be accumulated to elucidate these differences.
PMID- 25131183
TI - Targeting Th17 cells in autoimmune diseases.
AB - T helper 17 (Th17) cells have been implicated in the pathogenesis of most common
autoimmune diseases, including psoriasis, rheumatoid arthritis (RA), inflammatory
bowel disease (IBD), and multiple sclerosis (MS). Although anti-interleukin-17
(IL-17) antibodies show marked clinical efficacy in psoriasis, targeting IL-17
alone is not sufficient to improve clinical end points in other autoimmune
conditions, namely RA and Crohn's disease. Given that Th17 cells express IL-17
together with many other proinflammatory cytokines [IL-17F, IL-22, IL-26, and
granulocyte-macrophage colony-stimulating factor (GM-CSF)], targeting the Th17
cell lineage may be superior to blocking a single effector cytokine. Here, we
discuss the rationale for targeting two checkpoints in the development and
inflammatory function of Th17 cells, retinoid-related orphan receptor-gammat
(RORgammat) and IL-23, and we review recent progress in the development of both
RORgammat small molecule inhibitors and IL-23 neutralizing antibodies.
PMID- 25131184
TI - Factors influencing prostate-specific antigen response among men treated with
testosterone therapy for 6 months.
AB - INTRODUCTION: Factors influencing prostate-specific antigen (PSA) changes in men
undergoing testosterone (T) therapy have not been well studied. AIM: The aim of
this study was to assess the influence of selected variables on PSA changes in
hypogonadal men administered with 1.62% testosterone gel (T-gel) for 6 months.
METHODS: A double-blind, placebo-controlled study of 274 (234 T-gel, 40 placebo)
hypogonadal men >18 years of age, with baseline T concentrations <300 ng/dL, PSA
<=2.5 ng/mL, and negative digital rectal examination. Subjects received once
daily T-gel for T therapy. MAIN OUTCOME MEASURES: Changes in mean serum PSA,
percentage of free PSA (%fPSA), and T from baseline to 6 months (182 days).
RESULTS: Mean age was 53.5 years and baseline mean values were total T 247 ng/dL,
PSA 0.9 ng/mL, and %fPSA 24.6%. Among men treated with T-gel, T increased to 499
ng/dL and PSA increased by 0.1 ng/mL (P = 0.0012). PSA increased >=0.3 ng/mL in
26.3%, <0.3 ng/mL in 73.7%, including a decline from baseline in 33.0%. In the
placebo group, T increased 29 ng/dL to 274 ng/dL, and PSA decreased 0.1 ng/mL,
compared with baseline. A greater increase in PSA was noted in men >=60 years old
than in men <60 years old (0.4 vs. 0.05 ng/mL, respectively; P = 0.0006). Mean
PSA did not change in men with baseline serum T >250 ng/dL, whereas it increased
by 0.2 ng/mL in men with T <=250 ng/dL (P = 0.0031). PSA increased 0.3 ng/mL in
men with baseline %fPSA <20% and 0.1 ng/mL in men with %fPSA >=20%. CONCLUSIONS:
Overall, T-gel treatment was associated with a minor increase in PSA, of
questionable clinical significance. Factors predicting greater PSA increases
included age >=60 years, baseline T <=250 ng/dL, and %fPSA <20%. Men with T >250
ng/dL and age <60 years demonstrated minimal or no PSA change.
PMID- 25131185
TI - Surface confined heteroleptic copper(II)-polypyridyl complexes for photonuclease
activity.
AB - Heteroleptic copper(II)-polypyridyl complexes with extended pi-conjugated,
aromatic terminal units were immobilized on glass/Si substrates to intercalate
DNA and cleave it upon photoexposure. Photonuclease activity is shown to be high,
well reproducible and non-destructible towards the assembled complexes.
PMID- 25131186
TI - The Research Launchpad: measuring the efficiency and effectiveness of CTSA
resource and service provision.
PMID- 25131187
TI - In-vitro bipolar nano- and microsecond electro-pulse bursts for irreversible
electroporation therapies.
AB - Under the influence of external electric fields, cells experience a rapid
potential buildup across the cell membrane. Above a critical threshold of
electric field strength, permanent cell damage can occur, resulting in cell
death. Typical investigations of electroporation effects focus on two distinct
regimes. The first uses sub-microsecond duration, high field strength pulses
while the second uses longer (50 MUs+) duration, but lower field strength pulses.
Here we investigate the effects of pulses between these two extremes. The
charging behavior of the cell membrane and nuclear envelope is evaluated
numerically in response to bipolar pulses between 250 ns and 50 MUs. Typical
irreversible electroporation protocols expose cells to 90 monopolar pulses, each
100 MUs in duration with a 1 second inter-pulse delay. Here, we replace each
monopolar waveform with a burst of alternating polarity pulses, while keeping the
total energized time (100 MUs), burst number (80), and inter-burst delay (1s) the
same. We show that these bursts result in instantaneous and delayed cell death
mechanisms and that there exists an inverse relationship between pulse-width and
toxicity despite the delivery of equal quantities of energy. At 1500 V/cm only
treatments with bursts containing 50 MUs pulses (2*) resulted in viability below
10%. At 4000 V/cm, bursts with 1 MUs (100*), 2 MUs (50*), 5 MUs (20*), 10 MUs
(10*), and 50 MUs (2*) duration pulses reduced viability below 10% while bursts
with 500 ns (200*) and 250 ns (400*) pulses resulted in viabilities of 31% and
92%, respectively.
PMID- 25131188
TI - No impact of endogenous prothrombotic conditions on the risk of central venous
line-related thrombotic events in children: results of the KIDCAT study (KIDs
with Catheter Associated Thrombosis).
AB - BACKGROUND AND OBJECTIVE: Central venous lines (CVLs) are the major exogenous
risk factor for deep venous thrombosis (DVT) in children. The study objective was
to assess whether endogenous prothrombotic conditions contribute to the risk of
CVL-related DVT in children. METHODS: This was a cohort study of consecutive
children with heart disease requiring CVLs for perioperative care. CVLs were
inserted percutaneously in the upper venous system and patients received
prophylaxis with continuous unfractionated heparin (50 u kg(-1) d(-1) ). Blood
samples to test for prothrombotic conditions were collected prospectively and
assayed in a blinded fashion. Outcome assessment was by screening for DVT by
venography, venous ultrasound and echocardiography. RESULTS: The study population
consisted of 90 children, median age 2.7 years (0 months-18 years). Prevalence
rates of antithrombin deficiency, protein C deficiency, protein S deficiency,
heterozygous factor V Leiden, prothrombin G20210A mutation,
methylentetrahydrofolate C677TT genotype, hyperhomocysteinemia, lupus
anticoagulant, anticardiolipin antibodies and increased levels of lipoprotein (a)
were within the range reported for the general population. At least one
prothrombotic condition was present in 38% of children and combined abnormalities
in 8%. The incidence of DVT was 28% (25/90), and most DVTs were asymptomatic.
None of the prothrombotic conditions showed a significant association with DVT.
The population attributable risk (i.e. the risk of DVT in the overall population
attributable to a specific condition) did not exceed 2.2%. CONCLUSION:
Prothrombotic conditions did not have an important impact on the risk of DVT in
children with short-term CVLs. The results of the study suggest that screening
for prothrombotic conditions is not justified in this setting.
PMID- 25131189
TI - Evaluation of 18S rDNA PCR assay using skin fragments as a diagnostic test for
Trypanosoma caninum.
AB - Trypanosoma caninum is a new species that has been recently identified in Brazil
and infects domestic dogs. To date, no accurate diagnostic assays for this
parasite have been established; thus, our aim was to evaluate more than one type
of PCR for the diagnosis and molecular screening of T. caninum in 229 dogs living
in Rio de Janeiro state. The tests were based on the amplification and sequencing
of the 18S ribosomal DNA (rDNA) gene using healthy skin fragments. Additionally,
PCR amplification of the kDNA minicircles region specific to the Leishmania genus
was performed. The PCR results were compared with those of culture-based analysis
performed with the same specimen. Using cultures, T. caninum and Leishmania
chagasi were isolated from 11 and 12 dogs, respectively, whereas the 18S rDNA PCR
assay detected parasitic infection in 35 dogs. Among these, 25 dogs showed an
amplification pattern similar to T. caninum and 10 showed a pattern similar to L.
chagasi; these results were confirmed by sequencing analysis. The kDNA PCR
analysis showed that 14 dogs were positive for Leishmania infection. Of these, 2
dogs showed negative culture results and 12 were positive for L. chagasi,
including 4 with negative 18S rDNA PCR results. Thus far, culture-based testing
has been the only tool used successfully for T. caninum diagnosis. Our results
demonstrate that 18S rDNA PCR-based test should be a useful diagnostic tool,
particularly for distinguishing between T. caninum and L. chagasi infections in
areas where these 2 parasites co-exist.
PMID- 25131190
TI - On the use of posterior predictive probabilities and prediction uncertainty to
tailor informative sampling for parasitological surveillance in livestock.
AB - Model-based geostatistics and Bayesian approaches are appropriate in the context
of Veterinary Epidemiology when point data have been collected by valid study
designs. The aim is to predict a continuous infection risk surface. Little work
has been done on the use of predictive infection probabilities at farm unit
level. In this paper we show how to use predictive infection probability and
related uncertainty from a Bayesian kriging model to draw a informative samples
from the 8794 geo-referenced sheep farms of the Campania region (southern Italy).
Parasitological data come from a first cross-sectional survey carried out to
study the spatial distribution of selected helminths in sheep farms. A grid
sampling was performed to select the farms for coprological examinations. Faecal
samples were collected for 121 sheep farms and the presence of 21 different
helminths were investigated using the FLOTAC technique. The 21 responses are very
different in terms of geographical distribution and prevalence of infection. The
observed prevalence range is from 0.83% to 96.69%. The distributions of the
posterior predictive probabilities for all the 21 parasites are very
heterogeneous. We show how the results of the Bayesian kriging model can be used
to plan a second wave survey. Several alternatives can be chosen depending on the
purposes of the second survey: weight by posterior predictive probabilities,
their uncertainty or combining both information. The proposed Bayesian kriging
model is simple, and the proposed samping strategy represents a useful tool to
address targeted infection control treatments and surbveillance campaigns. It is
easily extendable to other fields of research.
PMID- 25131191
TI - Dysautonomic responses during percutaneous carotid intervention: principles of
physiology and management.
AB - Percutaneous carotid artery stenting (CAS) has emerged as a less invasive
alternative to carotid endarterectomy for the treatment of carotid
atherosclerotic disease. The main risk of CAS is the occurrence of neuro-vascular
complications; however, carotid artery stenting-related dysautonomia (CAS-D)
(hypertension, hypotension, and bradycardia) is the most frequently reported
problem occurring in the periprocedural period. Alterations in autonomic
homeostasis result from baroreceptor stimulation, which occurs particularly at
the time of balloon inflation in the region of the carotid sinus. The response
can be profound enough to induce asystole or even complete cessation of
postganglionic sympathetic nerve activity. Frequency and factors predisposing a
patient to CAS-D have been investigated in several studies; however, there are
significant discrepancies in results among reports. Lack of consistent findings
may arise from using different methods and definitions, as well as other factors
discussed in detail in this review. Furthermore, a correlation of CAS-D with
short and long-term outcomes has been investigated only in small and mostly
retrospective studies, explaining why its prognostic significance remains
uncertain. In this manuscript, we have focused on risk factors, pathophysiology
and management of periprocedural autonomic dysfunction. As there is no
standardized approach to the treatment of CAS-D, we present an algorithm for the
periprocedural management of patients undergoing CAS. The proposed algorithm was
developed based on our procedural experience as well as data from the available
literature. The Yale Algorithm was successfully implemented at our institution
and we are currently collecting data for short- and long-term safety. (c) 2014
Wiley Periodicals, Inc.
PMID- 25131193
TI - Pre-conception and diabetes: are we doing enough?
PMID- 25131192
TI - NEK9-dependent proliferation of cancer cells lacking functional p53.
AB - Dysfunction of the p53 network is a major cause of cancer development, and
selective elimination of p53-inactivated cancer cells therefore represents an
ideal therapeutic strategy. In this study, we performed a microRNA target screen
that identified NEK9 (NIMA-related kinase 9) as a crucial regulator of cell-cycle
progression in p53-inactivated cancer cells. NEK9 depletion selectively inhibited
proliferation in p53-deficient cancer cells both in vitro and in vivo. The
resultant cell-cycle arrest occurred predominantly in G1 phase, and exhibited
senescence-like features. Furthermore, NEK9 repression affected expression of a
broad range of genes encoding cell-cycle regulators and factors involved in mRNA
processing, suggesting a novel role for NEK9 in p53-deficient cells. Lung
adenocarcinoma patients with positive staining for NEK9 and mutant p53 proteins
exhibited significantly poorer prognoses, suggesting that expression of both
proteins promotes tumor growth. Our findings demonstrate that a novel NEK9
network regulates the growth of cancer cells lacking functional p53.
PMID- 25131194
TI - Diabetes and dementia in older people: a Best Clinical Practice Statement by a
multidisciplinary National Expert Working Group.
AB - Both dementia and diabetes mellitus are long-term disabling conditions and each
may be a co-morbidity of the other. Type 2 diabetes is associated with a 1.5- to
2-fold higher risk of dementia. Diabetes also may occur for the first time in
many individuals with mental ill health, including cognitive impairment and
dementia, and this may complicate management and lead to difficulties in self
care. Case finding is often poor for cognitive impairment in medical settings and
for diabetes in mental health settings and this needs to be addressed in the
development of care pathways for both conditions. Many other deficiencies in
quality care (both for dementia and diabetes) currently exist, but we hope that
this Best Clinical Practice Statement will provide a platform for further work in
this area. We have outlined the key steps in an integrated care pathway for both
elements of this clinical relationship, produced guidance on identifying each
condition, dealt with the potentially hazardous issue of hypoglycaemia, and have
outlined important competencies required of healthcare workers in both
medical/diabetes and mental health settings to enhance clinical care.
PMID- 25131195
TI - In-vivo imaging of the fracture healing in medaka revealed two types of
osteoclasts before and after the callus formation by osteoblasts.
AB - The fracture healing research, which has been performed in mammalian models not
only for clinical application but also for bone metabolism, revealed that
generally osteoblasts are induced to enter the fracture site before the induction
of osteoclasts for bone remodeling. However, it remains unknown how and where
osteoclasts and osteoblasts are induced, because it is difficult to observe
osteoclasts and osteoblasts in a living animal. To answer these questions, we
developed a new fracture healing model by using medaka. We fractured one side of
lepidotrichia in a caudal fin ray without injuring the other soft tissues
including blood vessels. Using the transgenic medaka in which osteoclasts and
osteoblasts were visualized by GFP and DsRed, respectively, we found that two
different types of functional osteoclasts were induced before and after
osteoblast callus formation. The early-induced osteoclasts resorbed the bone
fragments and the late-induced osteoclasts remodeled the callus. Both types of
osteoclasts were induced near the surface on the blood vessels, while osteoblasts
migrated from adjacent fin ray. Transmission electron microscopy revealed that no
significant ruffled border and clear zone were observed in early-induced
osteoclasts, whereas the late-induced osteoclasts had clear zones but did not
have the typical ruffled border. In the remodeling of the callus, the expression
of cox2 mRNA was up-regulated at the fracture site around vessels, and the
inhibition of Cox2 impaired the induction of the late-induced osteoclasts,
resulting in abnormal fracture healing. Finally, our developed medaka fracture
healing model brings a new insight into the molecular mechanism for controlling
cellular behaviors during the fracture healing.
PMID- 25131196
TI - Drosophila protein kinase N (Pkn) is a negative regulator of actin-myosin
activity during oogenesis.
AB - Nurse cell dumping is an actin-myosin based process, where 15 nurse cells of a
given egg chamber contract and transfer their cytoplasmic content through the
ring canals into the growing oocyte. We isolated two mutant alleles of protein
kinase N (pkn) and showed that Pkn negatively-regulates activation of the actin
myosin cytoskeleton during the onset of dumping. Using live-cell imaging analysis
we observed that nurse cell dumping rates sharply increase during the onset of
fast dumping. Such rate increase was severely impaired in pkn mutant nurse cells
due to excessive nurse cell actin-myosin activity and/or loss of tissue
integrity. Our work demonstrates that the transition between slow and fast
dumping is a discrete event, with at least a five to six-fold dumping rate
increase. We show that Pkn negatively regulates nurse cell actin-myosin activity.
This is likely to be important for directional cytoplasmic flow. We propose Pkn
provides a negative feedback loop to help avoid excessive contractility after
local activation of Rho GTPase.
PMID- 25131197
TI - Gas2l3 is essential for brain morphogenesis and development.
AB - Growth arrest-specific 2-like 3 (Gas2l3) is a newly discovered cell cycle protein
and a cytoskeleton orchestrator that binds both actin filament and microtubule
networks. Studies of cultured mammalian cells established Gas2l3 as a regulator
of the cell division process, in particular cytokinesis and cell abscission. Thus
far, the role of Gas2l3 in vivo remains entirely unknown. In order to investigate
Gas2l3 in developing vertebrates, we cloned the zebrafish gene. Spatiotemporal
analysis of gas2l3 expression revealed a ubiquitous maternal transcript as well
as a zygotic transcript primarily restricted to brain tissues. We next conducted
a series of loss-of-function experiments, and searched for developmental
anomalies at the end of the segmentation period. Our analysis revealed abnormal
brain morphogenesis and ventricle formation in gas2l3 knockdown embryos. This
signature phenotype could be rescued by elevated levels of gas2l3 RNA. At the
tissue level, gas2l3 downregulation interferes with cell proliferation,
suggesting that the cell cycle activities of Gas2l3 are essential for brain
tissue homeostasis. Altogether, this study provides the first insight into the
function of gas2l3 in vivo, demonstrating its essential role in brain
development.
PMID- 25131198
TI - Conversion of the thymus into a bipotent lymphoid organ by replacement of FOXN1
with its paralog, FOXN4.
AB - The thymus is a lymphoid organ unique to vertebrates, and it provides a unique
microenvironment that facilitates the differentiation of immature hematopoietic
precursors into mature T cells. We subjected the evolutionary trajectory of the
thymic microenvironment to experimental analysis. A hypothetical primordial form
of the thymus was established in mice by replacing FOXN1, the vertebrate-specific
master regulator of thymic epithelial cell function, with its metazoan ancestor,
FOXN4, thereby resetting the regulatory and coding changes that have occurred
since the divergence of these two paralogs. FOXN4 exhibited substantial
thymopoietic activity. Unexpectedly, histological changes and a functional
imbalance between the lymphopoietic cytokine IL7 and the T cell specification
factor DLL4 within the reconstructed thymus resulted in coincident but spatially
segregated T and B cell development. Our results identify an evolutionary
mechanism underlying the conversion of a general lymphopoietic organ to a site of
exclusive T cell generation.
PMID- 25131199
TI - The TSC complex is required for the benefits of dietary protein restriction on
stress resistance in vivo.
AB - Protein restriction (PR) is important for the benefits of dietary restriction on
longevity and stress resistance, but relevant nutrient sensors and downstream
effectors in mammals remain poorly defined. We used PR-mediated protection from
hepatic ischemia reperfusion injury to probe genetic requirements for the
evolutionarily conserved nutrient sensors GCN2 and mTORC1 in stress resistance.
One week of PR reduced free amino acids and circulating growth factors,
activating GCN2 and mTORC1 repressor tuberous sclerosis complex (TSC). However,
although GCN2 was dispensable for PR-induced protection, hepatic TSC1 was
required. PR improved hepatic insulin sensitivity in a TSC1-dependent manner
prior to ischemia, facilitating increased prosurvival signaling and reduced
apoptosis after reperfusion. These benefits were partially abrogated by
pharmacological PI3K inhibition or genetic deletion of the insulin receptor in
hepatocytes. In conclusion, improved insulin sensitivity upon short-term PR
required TSC1, facilitated increased prosurvival signaling after injury, and
contributed partially to PR-mediated resistance to clinically relevant ischemia
reperfusion injury.
PMID- 25131200
TI - A polymorphic enhancer near GREM1 influences bowel cancer risk through
differential CDX2 and TCF7L2 binding.
AB - A rare germline duplication upstream of the bone morphogenetic protein antagonist
GREM1 causes a Mendelian-dominant predisposition to colorectal cancer (CRC). The
underlying disease mechanism is strong, ectopic GREM1 overexpression in the
intestinal epithelium. Here, we confirm that a common GREM1 polymorphism,
rs16969681, is also associated with CRC susceptibility, conferring ~20%
differential risk in the general population. We hypothesized the underlying cause
to be moderate differences in GREM1 expression. We showed that rs16969681 lies in
a region of active chromatin with allele- and tissue-specific enhancer activity.
The CRC high-risk allele was associated with stronger gene expression, and higher
Grem1 mRNA levels increased the intestinal tumor burden in Apc(Min) mice. The
intestine-specific transcription factor CDX2 and Wnt effector TCF7L2 bound near
rs16969681, with significantly higher affinity for the risk allele, and CDX2
overexpression in CDX2/GREM1-negative cells caused re-expression of GREM1.
rs16969681 influences CRC risk through effects on Wnt-driven GREM1 expression in
colorectal tumors.
PMID- 25131202
TI - BRCA1 is a histone-H2A-specific ubiquitin ligase.
AB - The RING domain proteins BRCA1 and BARD1 comprise a heterodimeric ubiquitin (E3)
ligase that is required for the accumulation of ubiquitin conjugates at sites of
DNA damage and for silencing at DNA satellite repeat regions. Despite its links
to chromatin, the substrate and underlying function of the BRCA1/BARD1 ubiquitin
ligase remain unclear. Here, we show that BRCA1/BARD1 specifically ubiquitylates
histone H2A in its C-terminal tail on lysines 127 and 129 in vitro and in vivo.
The specificity for K127-129 is acquired only when H2A is within a nucleosomal
context. Moreover, site-specific targeting of the BRCA1/BARD1 RING domains to
chromatin is sufficient for H2Aub foci formation in vivo. Our data establish
BRCA1/BARD1 as a histone-H2A-specific E3 ligase, helping to explain its
localization and activities on chromatin in cells.
PMID- 25131201
TI - A macrohistone variant links dynamic chromatin compaction to BRCA1-dependent
genome maintenance.
AB - Appropriate DNA double-strand break (DSB) repair factor choice is essential for
ensuring accurate repair outcome and genomic integrity. The factors that regulate
this process remain poorly understood. Here, we identify two repressive chromatin
components, the macrohistone variant macroH2A1 and the H3K9 methyltransferase and
tumor suppressor PRDM2, which together direct the choice between the antagonistic
DSB repair mediators BRCA1 and 53BP1. The macroH2A1/PRDM2 module mediates an
unexpected shift from accessible to condensed chromatin that requires the ataxia
telangiectasia mutated (ATM)-dependent accumulation of both proteins at DSBs in
order to promote DSB-flanking H3K9 dimethylation. Remarkably, loss of macroH2A1
or PRDM2, as well as experimentally induced chromatin decondensation, impairs the
retention of BRCA1, but not 53BP1, at DSBs. As a result, macroH2A1 and/or PRDM2
depletion causes epistatic defects in DSB end resection, homology-directed
repair, and the resistance to poly(ADP-ribose) polymerase (PARP) inhibition-all
hallmarks of BRCA1-deficient tumors. Together, these findings identify dynamic,
DSB-associated chromatin reorganization as a critical modulator of BRCA1
dependent genome maintenance.
PMID- 25131203
TI - Perturbation of NCOA6 leads to dilated cardiomyopathy.
AB - Dilated cardiomyopathy (DCM) is a progressive heart disease characterized by left
ventricular dilation and contractile dysfunction. Although many candidate genes
have been identified with mouse models, few of them have been shown to be
associated with DCM in humans. Germline depletion of Ncoa6, a nuclear hormone
receptor coactivator, leads to embryonic lethality and heart defects. However, it
is unclear whether Ncoa6 mutations cause heart diseases in adults. Here, we
report that two independent mouse models of NCOA6 dysfunction develop severe DCM
with impaired mitochondrial function and reduced activity of peroxisome
proliferator-activated receptor delta (PPARdelta), an NCOA6 target critical for
normal heart function. Sequencing of NCOA6-coding regions revealed three
independent nonsynonymous mutations present in 5 of 50 (10%) patients with
idiopathic DCM (iDCM). These data suggest that malfunction of NCOA6 can cause DCM
in humans.
PMID- 25131204
TI - Evidence against a stem cell origin of new hepatocytes in a common mouse model of
chronic liver injury.
AB - Hepatocytes provide most liver functions, but they can also proliferate and
regenerate the liver after injury. However, under some liver injury conditions,
particularly chronic liver injury where hepatocyte proliferation is impaired,
liver stem cells (LSCs) are thought to replenish lost hepatocytes. Conflicting
results have been reported about the identity of LSCs and their contribution to
liver regeneration. To address this uncertainty, we followed candidate LSC
populations by genetic fate tracing in adult mice with chronic liver injury due
to a choline-deficient, ethionine-supplemented diet. In contrast to previous
studies, we failed to detect hepatocytes derived from biliary epithelial cells or
mesenchymal liver cells beyond a negligible frequency. In fact, we failed to
detect hepatocytes that were not derived from pre-existing hepatocytes. In
conclusion, our findings argue against LSCs, or other nonhepatocyte cell types,
providing a backup system for hepatocyte regeneration in this common mouse model
of chronic liver injury.
PMID- 25131205
TI - Stabilization of cartwheel-less centrioles for duplication requires CEP295
mediated centriole-to-centrosome conversion.
AB - Vertebrate centrioles lose their geometric scaffold, the cartwheel, during
mitosis, concurrently with gaining the ability to recruit the pericentriolar
material (PCM) and thereby function as the centrosome. Cartwheel removal has
recently been implicated in centriole duplication, but whether "cartwheel-less"
centrioles are intrinsically stable or must be maintained through other
modifications remains unclear. Here, we identify a newborn centriole-enriched
protein, KIAA1731/CEP295, specifically mediating centriole-to-centrosome
conversion but dispensable for cartwheel removal. In the absence of CEP295,
centrioles form in the S/G2 phase and lose their associated cartwheel in mitosis
but cannot be converted to centrosomes, uncoupling the two events. Strikingly,
centrioles devoid of both the PCM and the cartwheel progressively lose centriolar
components, whereas centrioles associating with either the cartwheel or PCM alone
can exist stably. Thus, cartwheel removal can have grave repercussions to
centriole stability, and centriole-to-centrosome conversion mediated by CEP295
must occur in parallel to maintain cartwheel-less centrioles for duplication.
PMID- 25131206
TI - Multilineage potential and self-renewal define an epithelial progenitor cell
population in the adult thymus.
AB - Thymic epithelial cells (TECs) are critical for T cell development and self
tolerance but are gradually lost with age. The existence of thymic epithelial
progenitors (TEPCs) in the postnatal thymus has been inferred, but their identity
has remained enigmatic. Here, we assessed the entire adult TEC compartment in
order to reveal progenitor capacity is retained exclusively within a subset of
immature thymic epithelium displaying several hallmark features of
stem/progenitor function. These adult TEPCs generate mature cortical and
medullary lineages in a stepwise fashion, including Aire+ TEC, within fetal
thymus reaggregate grafts. Although relatively quiescent in vivo, adult TEPCs
demonstrate significant in vitro colony formation and self-renewal. Importantly,
3D-cultured TEPCs retain their capacity to differentiate into cortical and
medullary TEC lineages when returned to an in vivo thymic microenvironment. No
other postnatal TEC subset exhibits this combination of properties. The
characterization of adult TEPC will enable progress in understanding TEC biology
in aging and regeneration.
PMID- 25131207
TI - Reconstruction of insulin signal flow from phosphoproteome and metabolome data.
AB - Cellular homeostasis is regulated by signals through multiple molecular networks
that include protein phosphorylation and metabolites. However, where and when the
signal flows through a network and regulates homeostasis has not been explored.
We have developed a reconstruction method for the signal flow based on time
course phosphoproteome and metabolome data, using multiple databases, and have
applied it to acute action of insulin, an important hormone for metabolic
homeostasis. An insulin signal flows through a network, through signaling
pathways that involve 13 protein kinases, 26 phosphorylated metabolic enzymes,
and 35 allosteric effectors, resulting in quantitative changes in 44 metabolites.
Analysis of the network reveals that insulin induces phosphorylation and
activation of liver-type phosphofructokinase 1, thereby controlling a key
reaction in glycolysis. We thus provide a versatile method of reconstruction of
signal flow through the network using phosphoproteome and metabolome data.
PMID- 25131208
TI - Nontranscriptional role of Hif-1alpha in activation of gamma-secretase and notch
signaling in breast cancer.
AB - gamma-Secretase is composed of four proteins that are obligatory for protease
activity: presenilin, nicastrin, Aph1, and Pen-2. Despite the progress toward
understanding the function of these individual subunits, there is no information
available pertaining to the modulation of gamma-secretase in response to
environmental changes in cells. Here, we show that hypoxia upregulates gamma
secretase activity through a direct interaction with Hif-1alpha, revealing an
unconventional function for Hif-1alpha as an enzyme subunit, which is distinct
from its canonical role as a transcription factor. Moreover, hypoxia-induced cell
invasion and metastasis are alleviated by either gamma-secretase inhibitors or a
dominant-negative Notch coactivator, indicating that gamma-secretase/Notch
signaling plays an essential role in controlling these cellular processes. The
present study reveals a mechanism in which gamma-secretase can achieve temporal
control through conditional interactions with regulatory proteins, such as Hif
1alpha, under select physiological and pathological conditions.
PMID- 25131210
TI - Dysregulated expression of neuregulin-1 by cortical pyramidal neurons disrupts
synaptic plasticity.
AB - Neuregulin-1 (NRG1) gene variants are associated with increased genetic risk for
schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased
expression of NRG1 in the brains of schizophrenia patients, given that both
findings have been reported from autopsy studies. To study NRG1 functions in
vivo, we generated mouse mutants with reduced and elevated NRG1 levels and
analyzed the impact on cortical functions. Loss of NRG1 from cortical projection
neurons resulted in increased inhibitory neurotransmission, reduced synaptic
plasticity, and hypoactivity. Neuronal overexpression of cysteine-rich domain
(CRD)-NRG1, the major brain isoform, caused unbalanced excitatory-inhibitory
neurotransmission, reduced synaptic plasticity, abnormal spine growth, altered
steady-state levels of synaptic plasticity-related proteins, and impaired
sensorimotor gating. We conclude that an "optimal" level of NRG1 signaling
balances excitatory and inhibitory neurotransmission in the cortex. Our data
provide a potential pathomechanism for impaired synaptic plasticity and suggest
that human NRG1 risk haplotypes exert a gain-of-function effect.
PMID- 25131211
TI - Sequencing of captive target transcripts identifies the network of regulated
genes and functions of primate-specific miR-522.
AB - Identifying microRNA (miRNA)-regulated genes is key to understanding miRNA
function. However, many miRNA recognition elements (MREs) do not follow canonical
"seed" base-pairing rules, making identification of bona fide targets
challenging. Here, we apply an unbiased sequencing-based systems approach to
characterize miR-522, a member of the oncogenic primate-specific chromosome 19
miRNA cluster, highly expressed in poorly differentiated cancers. To identify
miRNA targets, we sequenced full-length transcripts captured by a biotinylated
miRNA mimic. Within these targets, mostly noncanonical MREs were identified by
sequencing RNase-resistant fragments. miR-522 overexpression reduced mRNA,
protein levels, and luciferase activity of >70% of a random list of candidate
target genes and MREs. Bioinformatic analysis suggested that miR-522 regulates
cell proliferation, detachment, migration, and epithelial-mesenchymal transition.
miR-522 induces G1 cell-cycle arrest and causes cells to detach without anoikis,
become invasive, and express mesenchymal genes. Thus, our method provides a
simple but effective technique for identifying miRNA-regulated genes and
biological function.
PMID- 25131212
TI - Childhood florid follicular hyperplasia with immunoglobulin light-chain
restriction in the gastrointestinal tract.
AB - AIMS: Immunoglobulin light-chain expression is used routinely as an indirect
marker of clonality for recognizing B cell lymphoproliferative disorders. METHODS
AND RESULTS: Here we describe four floral follicular hyperplasia cases in the
gastrointestinal tract (appendix and rectum) of children (4 to 6 years).
Immunohistochemical studies revealed lambda light-chain restriction that was
associated with polyclonal IgH pattern. Clinical features and follow-up of the
patients did not reveal any other systemic symptoms, laboratory abnormalities or
organ alterations. CONCLUSIONS: Recognition of this phenomenon is useful in the
diagnosis of nodular lymphoid hyperplasia of the gastrointestinal tract, for
avoiding overdiagnosis of lymphoid malignancies, and raises concerns that the
identification of light-chain restriction is not necessarily a marker of
monoclonality.
PMID- 25131209
TI - Kcnn4 is a regulator of macrophage multinucleation in bone homeostasis and
inflammatory disease.
AB - Macrophages can fuse to form osteoclasts in bone or multinucleate giant cells
(MGCs) as part of the immune response. We use a systems genetics approach in rat
macrophages to unravel their genetic determinants of multinucleation and
investigate their role in both bone homeostasis and inflammatory disease. We
identify a trans-regulated gene network associated with macrophage
multinucleation and Kcnn4 as being the most significantly trans-regulated gene in
the network and induced at the onset of fusion. Kcnn4 is required for osteoclast
and MGC formation in rodents and humans. Genetic deletion of Kcnn4 reduces
macrophage multinucleation through modulation of Ca(2+) signaling, increases bone
mass, and improves clinical outcome in arthritis. Pharmacological blockade of
Kcnn4 reduces experimental glomerulonephritis. Our data implicate Kcnn4 in
macrophage multinucleation, identifying it as a potential therapeutic target for
inhibition of bone resorption and chronic inflammation.
PMID- 25131213
TI - Reconsidering the age thresholds for type II diabetes screening in the U.S.
AB - BACKGROUND: Type II diabetes and its complications can sometimes be prevented, if
identified and treated early. One fifth of diabetics in the U.S. remain
undiagnosed. Commonly used screening guidelines are inconsistent. PURPOSE: To
examine the optimal age cut-point for opportunistic universal screening, compared
to targeted screening, which is recommended by U.S. Preventive Services Task
Force (USPSTF) and American Diabetes Association (ADA) guidelines. METHODS: Cross
sectional analysis of a nationally representative sample from the National Health
and Nutrition Examination Survey, 2007-2010. Number of people needed to screen
(NNS) to obtain one positive test result was calculated for different guidelines.
Sampling weights were applied to construct national estimates. The 2010 Medicare
fee schedule was used for cost estimation. Analysis was conducted in January
2014. RESULTS: NNS, under universal screening, drops sharply at age 35 years,
from 80 (30-34-year-olds) to 31 (35-39-year-olds). Opportunistic universal
screening of eligible people aged >=35 years would yield an NNS of 15,
translating to $66 per positive test. Among people aged 35-44 years (who are not
recommended for universal screening by ADA), most (71%) were overweight or obese
and all had at least one other ADA risk factor. Only 34% of individuals aged >=35
years met USPSTF criteria. Strictly enforcing USPSTF guidelines would have
resulted in a majority (61%) of potential positive test cases being missed
(5,508,164 cases nationwide). CONCLUSIONS: Opportunistic universal screening
among individuals aged >=35 years could greatly reduce the national prevalence of
undiagnosed pre-diabetes or diabetes at relatively low cost.
PMID- 25131215
TI - End-of-life care in pediatric neuro-oncology.
AB - BACKGROUND: The management of children with cancer during the end-of-life (EOL)
period is often difficult and requires skilled medical professionals. Patients
with tumors of the central nervous system (CNS) with relapse or disease
progression might have additional needs because of the presence of unique issues,
such as neurological impairment and altered consciousness. Very few reports
specifically concerning the EOL period in pediatric neuro-oncology are available.
PROCEDURE: Among all patients followed at our center during the EOL, we
retrospectively analyzed data from 39 children and adolescents with brain tumors,
in order to point out on their peculiar needs. RESULTS: Patients were followed-up
for a median time of 20.1 months. Eighty-two percent were receiving only
palliative therapy before death. Almost half the patients (44%) died at home,
while 56% died in a hospital. Palliative sedation with midazolam was performed in
58% of cases; morphine was administered in 51.6% of cases. No patient had
uncontrolled pain. CONCLUSIONS: The EOL in children with advanced CNS cancer is a
period of active medical care. Patients may develop complex neurological symptoms
and often require long hospitalization. We organized a network-based
collaboration among the reference pediatric oncology center, other pediatric
hospitals and domiciliary care personnel, with the aim to ameliorate the quality
of care during the EOL period. In our cohort, palliative sedation was widely used
while no patients died with uncontrolled pain. A precise process of data
collection and a better sharing of knowledge are necessary in order to improve
the management of such patients.
PMID- 25131216
TI - Controlled release of beta-carotene in beta-lactoglobulin-dextran-conjugated
nanoparticles' in vitro digestion and transport with Caco-2 monolayers.
AB - Undesirable aggregation of nanoparticles stabilized by proteins may occur at the
protein's isoelectric point when the particle has zero net charge. Stability
against aggregation of nanoparticles may be improved by reacting free amino
groups with reducing sugars by the Maillard reaction. beta-Lactoglobulin (BLG)
dextran conjugates were characterized by SDS-PAGE and CD. Nanoparticles (60-70 nm
diameter) of beta-carotene (BC) encapsulated by BLG or BLG-dextran were prepared
by the homogenization-evaporation method. Both BLG and BLG-dextran nanoparticles
appeared to be spherically shaped and uniformly dispersed by TEM. The stability
and release of BC from the nanoparticles under simulated gastrointestinal
conditions were evaluated. Dextran conjugation prevented the flocculation or
aggregation of BLG-dextran particles at pH ~4-5 compared to very large sized
aggregates of BLG nanoparticles. The released contents of BC from BLG and BLG
dextran nanoparticles under acidic gastric conditions were 6.2 +/- 0.9 and 5.4 +/
0.3%, respectively. The release of BC from BLG-dextran nanoparticles by trypsin
digestion was 51.8 +/- 4.3% of total encapsulated BC, and that from BLG
nanoparticles was 60.9 +/- 2.9%. Neither BLG-BC nanoparticles nor the Maillard
reacted BLG-dextran conjugates were cytotoxic to Caco-2 cells, even at 10 mg/mL.
The apparent permeability coefficient (Papp) of Caco-2 cells to BC was improved
by nanoencapsulation, compared to free BC suspension. The results indicate that
BC-encapsulated beta-lactoglobulin-dextran-conjugated nanoparticles are more
stable to aggregation under gastric pH conditions with good release and
permeability properties.
PMID- 25131214
TI - Phenotypic spectrum associated with PTCHD1 deletions and truncating mutations
includes intellectual disability and autism spectrum disorder.
AB - Studies of genomic copy number variants (CNVs) have identified genes associated
with autism spectrum disorder (ASD) and intellectual disability (ID) such as
NRXN1, SHANK2, SHANK3 and PTCHD1. Deletions have been reported in PTCHD1 however
there has been little information available regarding the clinical presentation
of these individuals. Herein we present 23 individuals with PTCHD1 deletions or
truncating mutations with detailed phenotypic descriptions. The results suggest
that individuals with disruption of the PTCHD1 coding region may have subtle
dysmorphic features including a long face, prominent forehead, puffy eyelids and
a thin upper lip. They do not have a consistent pattern of associated congenital
anomalies or growth abnormalities. They have mild to moderate global
developmental delay, variable degrees of ID, and many have prominent behavioral
issues. Over 40% of subjects have ASD or ASD-like behaviors. The only consistent
neurological findings in our cohort are orofacial hypotonia and mild motor
incoordination. Our findings suggest that hemizygous PTCHD1 loss of function
causes an X-linked neurodevelopmental disorder with a strong propensity to
autistic behaviors. Detailed neuropsychological studies are required to better
define the cognitive and behavioral phenotype.
PMID- 25131218
TI - Low-magnitude high-frequency vibration enhances gene expression related to callus
formation, mineralization and remodeling during osteoporotic fracture healing in
rats.
AB - Low magnitude high frequency vibration (LMHFV) has been shown to improve anabolic
and osteogenic responses in osteoporotic intact bones and during osteoporotic
fracture healing; however, the molecular response of LMHFV during osteoporotic
fracture healing has not been investigated. It was hypothesized that LMHFV could
enhance osteoporotic fracture healing by regulating the expression of genes
related to chondrogenesis (Col-2), osteogenesis (Col-1) and remodeling (receptor
activator for nuclear factor- kappa B ligand (RANKL) and osteoproteger (OPG)). In
this study, the effects of LMHFV on both osteoporotic and normal bone fracture
healing were assessed by endpoint gene expressions, weekly radiographs, and
histomorphometry at weeks 2, 4 and 8 post-treatment. LMHFV enhanced osteoporotic
fracture healing by up-regulating the expression of chondrogenesis-, osteogenesis
and remodeling-related genes (Col-2 at week 4 (p=0.008), Col-1 at week 2 and 8
(p<0.001 and p=0.008) and RANKL/OPG at week 8 (p=0.045)). Osteoporotic bone had a
higher response to LMHFV than normal bone and showed significantly better results
as reflected by increased expression of Col-2 and Col-1 at week 2 (p<0.001 for
all), larger callus width at week 2 (p=0.001), callus area at week 1 and 5(p<0.05
for all) and greater relative area of osseous tissue (p=0.002) at week 8. This
study helps to understand how LMHFV regulates gene expression of callus
formation, mineralization and remodeling during osteoporotic fracture healing.
PMID- 25131217
TI - Late diagnosis of hepatitis C virus infection in the Chronic Hepatitis Cohort
Study (CHeCS): Missed opportunities for intervention.
AB - To determine the stage of liver disease at initial diagnosis of hepatitis C virus
(HCV) infection, we analyzed data from the Chronic Hepatitis Cohort Study
(CHeCS), a large U.S. observational study. We examined the temporal relationships
of initial HCV infection diagnosis with cirrhosis-defined by liver biopsy or mean
FIB-4 score >5.88-and time to onset of cirrhotic decompensation in electronic
medical records. We determined time in the health system prior to HCV diagnosis
and rates of hospitalization and death following HCV diagnosis. Of 14,717
patients with chronic HCV seen during 2006-2011, 6,166 (42%) had a definable time
of initial HCV diagnosis. Of these, 1,056 (17%) patients met our definition for
"late diagnosis" with either cirrhosis concurrent with initial HCV diagnosis (n =
550), a first diagnosis of hepatic decompensation before or within 12 months
after initial HCV diagnosis (n = 506), or both (n = 314). Patients with late
diagnosis had an average of 6 years in the health system before their HCV
diagnosis. In a comparison with patients without late diagnosis, hospitalization
(59% versus 35%) and death (33% versus 9%) were more frequent among patients with
late diagnosis. Among all who died, mean (median) time from initial HCV diagnosis
to death was 4.8 (4.2) years. CONCLUSION: Many CHeCS patients had advanced liver
disease concurrent with their initial HCV diagnosis despite many years of
engagement with the healthcare system, and these patients had high rates of
hospitalization and mortality.
PMID- 25131219
TI - Comparison of 2-limb versus 3-limb electrodiagnostic studies in the evaluation of
chronic inflammatory demyelinating polyneuropathy.
AB - INTRODUCTION: European Federation of Neurological Societies/Peripheral Nerve
Society electrodiagnostic (EDx) criteria for the definite diagnosis of chronic
inflammatory demyelinating polyneuropathy (CIDP) require the presence of
demyelinating findings (DF) in at least 2 nerves. Data are lacking, however,
regarding the optimal number of nerves to test. METHODS: We retrospectively
reviewed EDx data from 53 patients with CIDP and compared the number of DF found
on 2- and 3-limb testing. RESULTS: A median of 3 (range 2-5) DF were found on 2
limb testing compared with 5 (range 4-7) DF when 3 limbs were evaluated. Two-limb
EDx studies were sufficient to diagnose definite CIDP in 92.3% of typical, 84.2%
of asymmetric, and 66.7% of distal phenotypes. Testing a third limb increased
diagnostic certainty in 11 patients (20.8%) to definite CIDP. CONCLUSIONS: Three
limb testing may increase diagnostic sensitivity of definite CIDP, especially in
patients with atypical phenotypes. Larger prospective studies are needed to
better assess the benefit of performing 3-limb EDx studies.
PMID- 25131220
TI - Multi-omics analysis of inflammatory bowel disease.
AB - Crohn's disease and ulcerative colitis, known together as inflammatory bowel
disease (IBD), are severe autoimmune disorders now causing gut inflammation and
ulceration, among other symptoms, in up to 1 in 250 people worldwide. Incidence
and prevalence of IBD have been increasing dramatically over the past several
decades, although the causes for this increase are still unknown. IBD has both a
complex genotype and a complex phenotype, and although it has received
substantial attention from the medical research community over recent years, much
of the etiology remains unexplained. Genome-wide association studies have
identified a rich genetic signature of disease risk in patients with IBD,
consisting of at least 163 genetic loci. Many of these loci contain genes
directly involved in microbial handling, indicating that the genetic architecture
of the disease has been driven by host-microbe interactions. In addition,
systematic shifts in gut microbiome structure (enterotype) and function have been
observed in patients with IBD. Furthermore, both the host genotype and enterotype
are associated with aspects of the disease phenotype, including location of the
disease. This provides strong evidence of interactions between host genotype and
enterotype; however, there is a lack of published multi-omics data from IBD
patients, and a lack of bioinformatics tools for modeling such systems. In this
article we discuss, from a computational biologist's point of view, the potential
benefits of and the challenges involved in designing and analyzing such multi
omics studies of IBD.
PMID- 25131221
TI - Current status of anticoagulant treatments and improvements for hemodialysis
patients in northern Chinese cities: a five-year comparative study.
AB - BACKGROUND: Anticoagulation treatments are an important aspect of hemodialysis;
however, few reports have addressed these treatments. This investigation intends
to increase the understanding of the current status and improvements of
hemodialysis-related anticoagulation treatments in China. METHODS: In this study,
an epidemiological investigation was conducted that examined 842 patients in 2007
and 1 175 patients in 2012 who underwent hemodialysis anticoagulation treatments
in seven blood purification centers in northern Chinese cities. RESULTS: Heparin
was the most commonly used anticoagulant, although the percentage of use of low
molecular-weight heparin (LMWH) increased from 26.5% in 2007 to 42.1% in 2012. In
2007, there were no significant differences in anticoagulant selection among
either patients with various primary diseases or patients with hemorrhage,
thrombosis, thrombocytopenia, or a low hemoglobin level. However, compared with
patients with other diseases, significantly lower doses of LMWH were administered
to patients with hypertension (55.5 U/kg vs. 67.3 U/kg, P < 0.05) or diabetes
(58.5 U/kg vs. 67.3 U/kg, P < 0.05), and patients with hemorrhage received lower
doses of heparin than the other patients (61.6 U/kg vs. 71.8 U/kg, P < 0.01). In
2012, patients with diabetic nephropathy (51.5% vs. 36.5%, P < 0.01), hemorrhage
(43.4% vs. 31.7%, P < 0.01), or a hemoglobin level below 90 g/L (57.2% vs. 37.1%,
P < 0.01) experienced significantly higher doses of LMWH administration; patients
with hemorrhage received significantly reduced LMWH dosages (50.4 U/kg vs. 57.8
U/kg, P < 0.05), and patients with thrombosis received significantly higher doses
of heparin (73.8 U/kg vs. 62.1 U/kg, P < 0.01) or LMWH (57.8 U/kg vs. 52.6 U/kg,
P < 0.05). Antiplatelet drugs were administered to 20.4% of the examined patients
in 2007 and 20.7% in 2012. In 2012, patients with hypertension (25.9% vs. 18.5%,
P < 0.01) and thrombosis (36.6% vs. 16.1%, P < 0.01) had a higher rate of using
antiplatelet drugs than patients with other primary diseases and complications.
Patients receiving antiplatelet drugs also received higher doses of heparin than
patients without using antiplatelet drugs (74.4 U/kg vs. 65.9 U/kg, P < 0.01).
However, the use of the drugs was not correlated with thrombocytopenia. The rate
at which coagulation indices were determined increased from 45.7% in 2007 to 64%
in 2012. CONCLUSION: These findings suggested that hemodialysisrelated
anticoagulation treatments in China have gradually become more standardized and
individualized.
PMID- 25131222
TI - Diagnostic utility of N-terminal-proBNP in differentiating acute pulmonary
embolism from heart failure in patients with acute dyspnea.
AB - BACKGROUND: The plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP)
level is frequently elevated in dyspnoeic patients and increasingly used in
emergency departments to assess the cause of acute dyspnea. In this study we
prospectively tested NT-proBNP levels in patients with congestive heart failure
(CHF) and/or acute pulmonary embolism (APE) and determined the utility of NT
proBNP for discriminating APE from CHF. METHODS: A cohort of 177 dyspnoeic
patients with a diagnosis of APE and/or CHF was prospectively studied between
June 2010 and March 2013. NT-proBNP was measured by the electrochemiluminescence
immunoassay (ECLIA). All patients were evaluated with transthoracic
echocardiography (TTE). APE was diagnosed in the presence of thrombi signs in the
pulmonary arteries with computed tomographic pulmonary angiography (CTPA) or a
high-probability lung ventilation/perfusion scan. Risk stratification was based
on the evaluation on admission according to the ESC guidelines from 2008. The
diagnosis of CHF was based on the guidelines of the American College of
Cardiology/American Heart Association and the European Society of Cardiology. Two
physicians independently reviewed the records to determine the final diagnosis.
RESULTS: Fifty-nine patients met the criteria for dyspnea caused by APE, and 113
patients were diagnosed with CHF. Most of the APE patients (41, 69.5%) were
intermediate-risk. The symptoms and signs, such as orthopnea, paroxysmal
nocturnal dyspnea and rales in the lungs, were more common in patients with CHF
than in patients with APE (P < 0.01). Median NT-proBNP was significantly lower in
patients with APE compared to those in patients with CHF (2 855.9 pg/ml vs. 6
911.4 pg/ml, P < 0.01). We constructed the receiver operating characteristics
(ROC) curve in predicting the diagnosis of APE. At a cut point = 1 582.750 pg/ml,
NT-proBNP provided a specificity of 93% and a true positive rate (sensitivity) of
17% for the diagnosis. At a cut point = 3 390.000 pg/ml, NT-proBNP had a
specificity of 83% and a sensitivity of 84% for the diagnosis of APE. At a cut
point = 6 486.500 pg/ml, they were 54% and 93% respectively. CONCLUSIONS: NT
proBNP can assist in excluding CHF patients from those admitted to the emergency
department with acute dyspnea and identifying patients with a high probability of
APE, which would reduce the missed diagnosis of APE. Larger studies are necessary
to validate these findings.
PMID- 25131223
TI - Tartrate-resistant acid phosphatase 5b is a potential biomarker for rheumatoid
arthritis: a pilot study in Han Chinese.
AB - BACKGROUND: Bone damage around the joints is one of the major pathophysiological
mechanisms that leads to rheumatoid arthritis (RA) chronic disability. Serum
tartrate-resistant acid phosphatase 5b (TRACP-5b) is secreted by osteoclasts, its
activity can be used as a clinically relevant bone resorption marker. The aim of
this study was to test whether the measurement of serum levels of TRACP-5b in
patients with RA would correlate with measures of disease activity and with
responses to therapy. METHODS: Fifty-six patients were randomly assigned to
receive recombinant human cytotoxic tlymphocyte-associated antigen-4
immunoglobulin (RhCTLA4-Ig), infliximab or methotrexate (MTX). The clinical and
serologic indicators of RA activity were evaluated at baseline and at 24 weeks.
Serum TRACP-5b was measured by Enzyme-linked Immunosorbent Assay (ELISA) at 0, 12
and 24 weeks. Hand X-rays were obtained at baseline. RESULTS: At baseline, the
levels of TRACP-5b correlated with the severity of X-ray damage, disease duration
(r = 0.332, P = 0.012), and tender joint count (r = 0.408, P = 0.002). The 24
weeks values of TRACP-5b for RhCTLA4-Ig group and infliximab group differed
significantly from the baseline values in each group (P < 0.05; P < 0.05),
whereas only the value for RhCTLA4-Ig group differed significantly from the 24
weeks value for the MTX group (P < 0.01). Considering the two biologics-treated
groups together, the TRACP-5b levels at 24 weeks differed significantly from the
baseline values only in those patients who reached an ACR70 level (P < 0.05).
CONCLUSIONS: Measurement of serum TRACP-5b in RA patients reflects clinical and
radiological measures of disease activity, treatment with certain biologics, and
degree of response to therapy. TRACP-5b should be investigated further as a
potential biomarker to predict response to therapy, including slowing of
radiographic progression.
PMID- 25131224
TI - Augmentation plating in hypertrophic non-union after nail fixation of femoral
shaft fracture compared with exchange plating.
AB - BACKGROUND: Augmentation plating has been used successfully to treat hypertrophic
non-union after nail fixation. This study compared the efficacy of augmentation
plating and exchange plating for treating hypertrophic non-union of femoral shaft
fracture after intramedullary nail fixation. METHODS: A total of 12 patients
received augmentation plating and 15 patients received exchange plating as
treatment for femoral shaft hypertrophic non-union. The procedures were conducted
at our medical centre between January 2005 and January 2012. Clinical follow-up
was conducted at 2 weeks, 1 month and then monthly until union was achieved to
compare union time, operation time, bleeding and complications between the two
groups. RESULTS: All patients underwent follow-up examinations until fracture
union was achieved. The average length of follow-up time after the second
treatment was (18.37 +/- 3.28) months. The time needed for union was (4.17 +/-
0.94) months in the augmentation plating group and (5.33 +/- 1.72) months in the
exchange plating group. The operation time was (90.00 +/- 17.58) minutes in the
augmentation plating group and (160.00 +/- 25.35) minutes in the exchange plating
group. The amount of blood loss during the operation was (270.00 +/- 43.32) ml in
the augmentation plating group and (530.00 +/- 103.65) ml in the exchange plating
group. Both groups showed significant difference (P < 0.05) in their results. No
complications were reported after the second operation. CONCLUSIONS: Augmentation
plating after nail fixation could remove local rotation instability, facilitate
simple operation, create minimal damage and enable exercise for early functional
recovery. Therefore, augmentation plating is excellent for treating hypertrophic
non-union after nail fixation in femoral shaft fracture.
PMID- 25131225
TI - Intravitreal ranibizumab for the treatment of pathological myopia associated with
choroidal neovascularization in Chinese patients.
AB - BACKGROUND: Pathological myopia (PM) is the leading cause for choroidal
neovascularization (CNV) in people below 50 years of age, the anti-vascular
endothlial growth factor (VEGF) medicine is now available to treat CNV secondary
to PM. This study aimed to observe the efficacy of intravitreal ranibizumab for
PM associated with subfoveal or juxtafoveal CNV in Chinese patients. METHODS:
Fifty-four eyes of 52 consecutive patients were included, they treated with
intravitreal ranibizumab 0.5 mg for PM associated with CNV. The best corrected
visual acuity (BCVA) of Snellen chart, letters of ETDRS chart, retinal thickness,
leakage of CNV lesion, and complications with surgery were analyzed pre- and post
treatment. Eligibility criteria included diopter >=-8.0 D or eye axis >= 28 mm
with fundus changes of PM (lacquer crack, optic disc atrophy, chorioretinal
atrophy, posterior scleral staphyloma); CNV secondary to PM; subfoveal or
juxtafoveal CNV. RESULTS: For 54 affected eyes of 52 consecutive patients, the
average BCVA of Snellen chart and letters of ETDRS chart were 0.29 and 30.4,
respectively; fundus fluorescein angiography (FFA)/indocyanine green angiography
(ICGA) showed CNV leakage, and average retinal thickness on optical coherence
tomography (OCT) was 267.2 um before treatment. Injections of ranibizumab ranged
from 1 to 4 (mean 2.2). Follow-up time varied from 12 to 36 months (mean 31.9
months). At the last visit, the BCVA of Snellen chart was increased by three
lines (mean 0.65) (P < 0.01); the letters of ETDRS chart were increased to 17.0
letters (mean 47.4, P < 0.01); the visual acuity increased more than 15 letters
in 30 eyes (55.5%), decreased in 1 eye (1.9%); the retinal thickness on OCT
images was decreased by 17.0 um (mean 250.2 um) (P = 0.082); no active leakage
from the CNV lesion occurred in 18 eyes (33.3%), reduced leakage in 30 eyes
(55.6%), and no change in 6 eyes (11.1%) as shown by FFA/ICGA. Increased
retinoschisis was observed in one eye after the second injection. CONCLUSIONS:
Intravitreal ranibizumab for neovascular PM was well tolerated in Chinese
patients, with functional and anatomic improvements in a short-term study, while
a long-term study is still needed.
PMID- 25131226
TI - Strabismus surgery distribution during 10-year period in a tertiary hospital.
AB - BACKGROUND: There is no large population-based study of the distribution and
changing trend of strabismus surgeries in China. This study aimed to investigate
the distribution and the changing trend of strabismus surgery in a tertiary
hospital of China. METHODS: A retrospective study of all the strabismus surgeries
performed in Beijing Tongren Eye Center from 2003 to 2012 was carried out.
Characteristics analyzed included the type of strabismus, age, and gender.
RESULTS: Totally 26 524 strabismus surgeries were performed in Tongren Eye Center
during the 10-year period. The number of surgeries increased steadily from 1 507
in 2003 to 3 482 in 2008 and slightly decreased to 3 124 in 2009, but there was a
sharp drop to 2 569 in 2010 and then kept relatively steady at 2 760 in 2011 and
2 463 in 2012. Intermittent exotropia (30.3%) was the most common among all kinds
of strabismus. The number of strabismus surgeries performed on children under 12
years of age (43.60%) was significantly higher than those of the other age groups
(P < 0.05). Unilateral superior oblique paralysis was the most common subtype of
paralytic strabismus (8.64%). CONCLUSIONS: The type distribution of strabismus
surgery has changed during the recent decade. The age and type distribution of
different strabismus remained basically constant, among which intermittent
exotropia was the most common.
PMID- 25131227
TI - Relationship between chronic diarrhea with normal colonoscopy findings and
terminal ileum lesions.
AB - BACKGROUND: The causes and mechanisms of chronic diarrhea are complex. This study
aimed to explore the relationship between chronic diarrhea with normal
colonoscopy findings and terminal ileum lesions. METHODS: All cases were
collected from January 2009 to June 2010. The 40 patients in the patient group
had chronic diarrhea with normal colonoscopy findings. Those who had
hyperthyroidism, diabetes, chronic pancreatitis, cirrhosis, atrophic gastritis,
short bowel syndrome and connective tissue diseases had been excluded. The
control group contained 40 healthy individuals without diarrhea. Endoscopy of the
terminal ileum was applied in both groups, with the endoscope inserted into
terminal ileum for more than 20 cm. The patients diagnosed of chronic diarrhea
with terminal ileum lesions were treated with metronidazole and probiotics for 10
14 days. RESULTS: Before treatment there were significant differences in
endoscopy findings of the terminal ileum between the two groups (P < 0.05). In
the patient group, endoscopy showed congestion, edema, erosion and ulcers in 29
cases, hyperplasia and enlargement of lymphoid follicles in 10 cases with a
maximal diameter of 7-8 mm, and 1 case showed normal endoscopy results. After
treatment, 35 patients recovered from diarrhea, and terminal ileum lesions
disappeared in 30 cases as determined by endoscopy. In the control group,
endoscopy showed scattered hyperplasia of lymphoid follicles in 5 cases, and the
follicles were small with the maximal diameter being 3 mm. There was no
hyperemia, edema, erosion or ulcers. CONCLUSIONS: Chronic diarrhea patients with
normal colonoscopy findings may have lesions in the terminal ileum that can be
detected by endoscopy; including hyperemia, erosion, ulcers and lymphoid follicle
hyperplasia. Therapeutic effect is good with metronidazole and probiotics.
PMID- 25131228
TI - Prognosis of R1-resection at the bronchial stump in patients with non-small cell
lung cancer.
AB - BACKGROUND: The prognosis of R1-resection at the bronchial stump in patients with
non-small cell lung cancer (NSCLC) remains unclear. This study intends to
identify the prognostic factors and to optimize treatments for these patients
under update conditions. METHODS: The data of 124 NSCLC patients who underwent R1
resection at the bronchial stump was reviewed. There were 41 patients in the
surgery group (S), 21 in the postoperative radiotherapy (PORT) group (S+R), 30 in
the postoperative chemotherapy (POCT) group (S+C), and 32 in the PORT plus POCT
group (S+R+C). The constitute proportion in different groups was tested using the
chi(2) method, univariate analysis was performed using the Kaplan-Meier and log
rank method, and multivariate analysis was done using the Cox hazard regression
with entry factors including age, sex, pathological type and stage,
classification of the residual disease, and treatment procedure. The process was
performed stepwise backward with a maximum iteration of 20 and an entry
possibility of 0.05 as well as an excluded possibility of 0.10 at each step.
RESULTS: In univariate analysis, survival was more favorable for patients with
squamous cell carcinoma, early pathological T or N stage, and chemotherapy or
radiotherapy. There was no significant difference in the survival for patients
with different types of the residual disease, except for the difference between
patients with carcinoma in situ and lymphangiosis carcinomatosa (P = 0.030). The
survival for patients receiving chemoradiotherapy was superior to that for those
undergoing surgery alone (P = 0.016). In multivariate analysis, the pathological
type (HR 2.51, 95% CI 1.59 to 3.96, P = 0.000), pathological T (HR 1.29, 95% CI
1.04 to 1.60, P = 0.021) or N stage (HR 2.04, 95% CI 1.40 to 2.98, P = 0.000),
and chemotherapy (HR 0.24, 95% CI 0.13 to 0.43, P = 0.000) were independent
prognostic factors. CONCLUSION: Patients with squamous cell carcinoma, early
pathological T or N stage, or receiving chemotherapy had a more favorable
prognosis.
PMID- 25131229
TI - Analysis of risk factors affecting the prognosis of pancreatic neuroendocrine
tumors.
AB - BACKGROUND: Pancreatic neuroendocrine tumors (pNETs) are a type of tumors with
the characteristics of easy metastasis and recurrence. Till date, the risk
factors affecting the prognosis are still in the debate. In this study, several
risk factors will be discussed combined with our cases and experience. METHODS:
Thirty-three patients diagnosed as pNETs were enrolled and the clinical features,
blood tests, pathological features, surgical treatment, and follow-up data of
these patients were collected and analyzed. RESULTS: In this study, operation
time of G3 cases was longer than G1/G2 cases (P = 0.017). The elevated level of
tumor markers such as AFP, CEA, Ca125, and Ca19-9 may predict easier metastasis,
earlier recurrence, and poor prognosis (P = 0.007). The presence of cancer
embolus and nerve invasion increases along with the TNM stage (P = 0.037 and P =
0.040), and the incidence of positive surgical margin increased (P = 0.007). When
the presence of nerve invasion occurs, the chance of cancer embolus and lymph
node metastasis also increases (P = 0.016 and P = 0.026). CONCLUSIONS: pNETs were
tumors with the features of easy recurrence and metastasis and many risk factors
could affect its prognosis such as the elevated levels of tumor markers and the
presence of nerve invasion, except some recognized risk factors. If one or more
of these factors existed, postoperative treatments may be needed to improve
prognosis.
PMID- 25131230
TI - Effect of fixing distal radius fracture with volar locking palmar plates while
preserving pronator quadratus.
AB - BACKGROUND: L-shaped incision of pronator quadratus (PQ) muscle along its radial
and distal borders was always taken for distal radius fractures reduction and
internal fixation. Repair of the PQ muscle was always recommended at the end of
operation for some instructive reasons. But repair of PQ is not satisfied because
of poor quality of muscle and fascial tissues which may cause pain or impede
forearm pronation and supination for post-operative scarring around PQ. Inserting
the locking palmar plate to pass under the pronator quadratus muscle and the
locking screws are inserted through mini-incisions in pronator quadratus in some
patients with distal radius fractures is a reasonable technique which can
preserve the pronator quadratus. The purpose of this study was to evaluate and
compare the clinical effects after volar plating of the distal radius fractures
while preserving the pronator quadratus and pronator quadratus repair. METHODS:
Between September 2010 and April 2012, 65 patients (42 males and 23 females; aged
20-68 years and a mean age of 42.5 years) with distal radius fracture underwent
open reduction and internal fixation using the volar locking palmar plates (Depuy
or Smith companies). The patients were classified as 23A-2 through 23C-3
according to the Orthopaedic Trauma Association (OTA) classifications. All
surgeries were completed by the same trained team. The volar locking palmar
plates of distal radius performed with preserving pronator quadratus group
involved 30 patients including 19 males and 11 females and performed with
pronator quadratus repair group involved 35 patients including 23 males and 12
females. We compared the two groups for wrist pain, forearm range of motion, grip
strength, perioperative complications and wrist functional recovery score.
RESULTS: The minimum follow-up for the whole cohort was one year. The differences
between the two groups were significant with regard to wrist pain, forearm range
of motion, grip strength and wrist function at 1, 2, and 6 weeks postoperatively,
but insignificant at 6 and 12 months postoperatively. No significant differences
were found in the perioperative complications and radiographs postoperatively.
CONCLUSIONS: Preservation of the pronator quadratus muscle is a satisfactory
method for the treatment of majority of the fractures of the distal radius with
volar locking palmar plates, as this technique can yield better early wrist
function and shorten the rehabilitation.
PMID- 25131231
TI - En bloc resection concept for endoscopic endonasal nasopharyngectomy: surgical
anatomy and outcome.
AB - BACKGROUND: Nasopharyngeal carcinoma (NPC) patients have a 19%-56% locoregional
recurrence rate after primary therapy. For those recurrent NPC (rNPC) patients,
re-irradiation may cause some complications. In recent years, endoscopic
endonasal nasopharyngectomy (EEN) has become a surgical option for rNPC patients.
Here we introduce the concept of en bloc excision (EBE) technique for EEN,
including the surgical technique and clinical outcomes. METHODS: A retrospective
study was conducted covering September 2009 to May 2013, involving the collection
of locoregional rNPC cases from two institutions (Kuang-Tien General Hospital
(KTGH) in Taiwan and National University Health System (NUHS) in Singapore).
These patients failed prior therapy and then underwent EEN. We reported the 2
year overall survival rate, the 2-year disease-free survival rate, and related
complications. RESULTS: Nine patients (five from KTGH and four from NUHS)
completed this study, with five, two, and two patients of recurrence tumors
(rT1), rT2, and rT3, respectively. The mean age was 46.4 years (range 32-63); the
mean follow-up period was 24.9 months (range 10-45). The 2-year survival rate and
the 2-year disease-free rate were 100% and 80%, respectively, in five patients.
No significant complications or cases of mortality occurred. CONCLUSIONS: The EBE
concept of EEN is suitable for early rT1 and has relatively encouraging short
term outcomes. In selected rT2, careful EBE can be performed by expanding the
surgical field. A clear view of the internal carotid artery-related anatomy is
indispensable. In the future, more series may be needed to determine the role of
EEN in rNPC patients.
PMID- 25131232
TI - Influence of tube voltage on digitized image qualityof patients exposed to
occupational dust: phantoms and clinical studies.
AB - BACKGROUND: High-voltage analog X-ray examination is a main tool for
pneumoconiosis, which is challenged by digital radiography (DR). The tube voltage
of DR chest films required for diagnosis and staging of pneumoconiosis is
concerned technically. We investigated the influence of the tube voltage on chest
X-ray DR image quality of patients exposed to occupational dust. METHODS: DR
images of the CDRAD2.0model, an anatomical chest phantom, and 136 exposed workers
were analyzed at different tube voltages by threereaders. Image quality factors
(IQF) were calculated and compared using the CDRAD2.0 model. DR images of ten
anatomic positions were scored against those of the high-kilovolt chest films in
anatomical phantom and clinical cases, and differences in scores were analyzed.
RESULTS: In the CDRAD2.0 model, all three readers had a minimal IQF at 120 kV
(mean: 22.25 kV). The differences in the mean IQF of DR images at different tube
voltages was significant (F = 13.78, P < 0.001). The IQF of DR imaging at 120 kV
was similar to high kilovolt analog imaging (t = -0.58, P > 0.05). In the
anatomic phantom and clinical cases, the DR images at 120 kV were closest in
anatomical detail to the high kV analog images, and the means were similar (P >
0.05). CONCLUSIONS: Among different tube voltages, DR image quality is closest to
the high kilovolt analog images at 120 kV in patients exposed to occupational
dust.
PMID- 25131233
TI - Dynamic long-term microstructural and ultrastructural alterations in sensory
nerves of rats of paclitaxel-induced neuropathic pain.
AB - BACKGROUND: Paclitaxel, as a first line anti-neoplastic compound, frequently
produces long-term pain after tumors have been treated. Clinical manifestations
are varied and non-specific. Pathology of the nervous system during the
development of the neuropathic pain is unclear. Thus, early diagnosis and
treatment is often unsatisfying for patients. This study aimed to promote
considerate understanding of the structural alteration of sensory nerves.
METHODS: All rats were simply randomized into 3 groups: paclitaxel group, vehicle
group and saline group. An established rat model of paclitaxel-induced peripheral
neuropathy (2 mg/kg) was chosen for our research, behavior tests were operated
during the procedure of 56 days. All rats were sampled on days 0, 3, 7, 28 and
56. The hind paw plantar skin, sciatic nerves, dorsal root ganglion and attached
fibers, and lumbar spinal cord were processed for light and electron microscopy.
The differences among 3 groups were analyzed with one-way analysis of variance
(ANOVA). RESULTS: We affirmed that paclitaxel-induced mechano-allodynia and
mechano-hyperalgesia occured after a 3-7-day delay, and this pain peaked at day
28 and persisted to day 56. Paclitaxel and vehicle treatment both evoked thermal
hyperalgesia. Paclitaxel-induced axonal and myelin sheath degeneration was
evident. At days 3 and 7, significant increases in atypical mitochondria in both
myelinated axons and C-fibers of paclitaxel-treated nerves indicated that injured
mitochondria correlated to specific paclitaxel-induced neuropathic pain, and the
abnormity sustained till day 56. Microtubule was unaffected in myelinated axons
or C-fibers in paclitaxel- or vehicle-treated rats. Significant increase of G
ratio was evident with paclitaxel injection at days 7 and 28. CONCLUSION: Our
research suggests a causal role for axonal degeneration, abnormalities in axonal
mitochondria, and structural modification of axonal microtubules in paclitaxel
induced neuropathic pain, and the abnormal mitochondria could be connected to the
chronic neuropathic pain.
PMID- 25131234
TI - Short-term intensive atorvastatin therapy improves endothelial function partly
via attenuating perivascular adipose tissue inflammation through 5-lipoxygenase
pathway in hyperlipidemic rabbits.
AB - BACKGROUND: Atherosclerosis is a kind of disease with multiple risk factors, of
which hyperlipidemia is a major classical risk factor resulting in its
pathogenesis and development. The aim of this study was to determine the effects
of short-term intensive atorvastatin (IA) therapy on vascular endothelial
function and explore the possible mechanisms that may help to explain the
clinical benefits from short-term intensive statin therapy. METHODS: After
exposure to high-fat diet (HFD) for 8 weeks, the animals were, respectively,
treated with IA or low-dose atorvastatin (LA) for 5 days. Blood lipids, C
reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6
(IL-6), nitric oxide (NO), endothelin-1 (ET-1), and endothelium-dependent
vasorelaxation function were, respectively, measured. mRNA and protein expression
of CRP, TNF-alpha, IL-6, macrophage chemoattractant protein-1 (MCP-1), and 5
lipoxygenase (5-LO) were also evaluated in pericarotid adipose tissue (PCAT) and
cultured adipocytes. RESULTS: HFD increased serum inflammatory factor levels;
induced significant hyperlipidemia and endothelial dysfunction, including
imbalance between NO and ET-1; enhanced inflammatory factors and 5-LO expression;
and promoted macrophage infiltration into adipose tissue. Five-day IA therapy
could significantly decrease serum inflammatory factor levels and their
expression in PCAT; restore the balance between NO and ET-1; and improve
endothelial function and macrophage infiltration without significant changes in
blood lipids. However, all of the above were not observed in LA therapy. In vitro
experiment found that lipopolysaccharide (LPS) enhanced the expression of
inflammatory factors and 5-LO in cultured adipocytes, which could be attenuated
by short-time (6 hours) treatment of high-dose (5 umol/L) but not low-dose (0.5
umol/L) atorvastatin. In addition, inhibiting 5-LO by Cinnamyl-3,4-dihydroxy
alpha-cyanocinnamate (CDC, a potent and direct 5-LO inhibitor) could
significantly downregulate the above-mentioned gene expression in LPS-treated
adipocytes. CONCLUSION: Short-term IA therapy could significantly ameliorate
endothelial dysfunction induced by HFD, which may be partly due to attenuating
inflammation of PCAT through inhibiting 5-LO pathway.
PMID- 25131235
TI - Iloprost inhibits fracture repair in rats.
AB - BACKGROUND: Previous studies have shown that prostaglandins (PGs) dramatically
stimulate healing processes in bone. However, the effect of prostaglandin I2
(PGI2) on fracture healing remains unclear. To investigate the effect of PGI2, a
study on fracture healing process in closed tibia fractures was designed.
METHODS: Thirty-six Sprague-Dawley male rats were randomized into two groups. On
the first day, their right tibias were fractured by three-point bending
technique. The study group (n = 18) received a single injection of 10 ug/kg
iloprost for 5 days, while the control group (n = 18) received saline solution in
the same way. On the 7th, 14th and 28th days following the fracture, six rats
were sacrificed and their right legs were harvested in each group. The
progression of fracture healing was assessed for each specimen by the scores of
radiography (by Lane-Sandhu) and histology (by Huo et al). RESULTS: On the 7th
day, the radiographic and histologic scores were equal. On the 14th day
radiographic total score was 6 and histologic total score was 23 in the iloprost
group, whereas radiographic total score was 11 and histologic total score was 33
in the control group. On the 14th day radiographic and histologic scores were
significantly decreased in the iloprost group compared to the control group (P <
0.05). On the 28th day radiographic total score was 12 and histologic total score
was 37 in the iloprost group, whereas radiographic total score was 15 and
histologic total score was 40 in the control group. On the 28th day although
there was a decrease in radiographic and histologic scores of the iloprost group
acording to control group, it was not statistically significant (P > 0.05).
CONCLUSION: Iloprost delays fracture healing in early stage in rats.
PMID- 25131236
TI - Effect and mechanism of tacrolimus on melanogenesis on A375 human melanoma cells.
AB - BACKGROUND: Topical tacrolimus has been used for vitiligo as a common treatment
option for more than ten years while the underlying mechanism is still uncertain.
The aim of this study was to investigate the direct effects of tacrolimus on the
melanogenesis and migration on human A375 melanoma cells. The expression of c-KIT
mRNA and protein of human A375 cells were also investigated. METHODS: The
cultured A375 human melanoma cells were randomly assigned to control and
tacrolimus treatment groups (10, 10(2), 10(3) and 10(4) nmol/L). The cell
proliferation was measured with Cell Counting Kit-8 assays. Melanin content was
measured with NaOH method. Transwell migration assay was used to measure cell
migration. The expression of c-KIT mRNA and protein were measured with real-time
fluorescence quantitative polymerase chain reaction and immunohistochemistry
respectively. RESULTS: The cell proliferation of the 10(3) and 10(4) nmol/L
tacrolimus groups were significantly lower (0.666 +/- 0.062 and 0.496 +/- 0.038)
as compared with the control (0.841 +/- 0.110, P < 0.05). The mean melanin
content in all groups treated with different concentration of tacrolimus (10,
10(2), 10(3), 10(4) nmol/L) increased compared with the control group (P < 0.05).
Dose-dependent increase in cell migration were seen in all tacrolimus-treated
groups (P < 0.01). The expression of c-KIT mRNA level in A375 cells exposed to
tacrolimus (10(3) and 10(4) nmol/L) had significantly increased by 3.03-fold and
3.19-fold respectively compared with the control (P < 0.05). CONCLUSIONS:
Although tacrolimus had no effects on cell proliferation on A375 human melanoma
cells, it could increase the melanin content and cell migration. The expression
of c-KIT mRNA and protein increased dose-dependently in tacrolimus-treated groups
as compared with the control. Our study demonstrated that tacrolimus could
enhance the melanogenesis and cell migration on A375 cells.
PMID- 25131237
TI - Reinnervation of hair cells by neural stem cell-derived neurons.
AB - BACKGROUND: Replacement of spiral ganglion neurons would be one prioritized step
in an attempt to restore sensory neuronal hearing loss. However, the possibility
that transplanted neurons could regenerate new synaptic connections to hair cells
has not been explored. The objective of this study was to test whether neural
stem cell (NSC)-derived neurons can form synaptic connections with hair cells in
vitro. METHODS: NSCs were mechanically separated from the hippocampus in SD rat
embryos (E12-E14) and cultured in a serum-free medium containing basic fibroblast
growth factor and epidermal growth factor. Rat NSCs were co-cultured with
explants of cochlea sensory epithelia obtained from postnatal Day 3 rats under
transway filter membrane. RESULTS: At Day 3, the NSCs began to show chemotactic
differentiation and grew toward cochlea sensory epithelia. After 9-day co
culture, neurites of NSC-derived neurons predominantly elongated toward hair
cells. Immunohistochemical analyses revealed the fibers overlapped with synapsin
and hair cells, indicating the formation of new synaptic connections. After 14
day culture, triple staining revealed the fibers overlapped with PSD95
(postsynaptic density) which is juxtaposed with CtBP2 (presynaptic vesicle),
indicating the formation of new ribbon synapse. CONCLUSIONS: NSC-derived neurons
can make synaptic connections with hair cells and provide a model for studying
synaptic plasticity and regeneration. Whether the newly forming synapse is
functional merits further electrophysiological study.
PMID- 25131238
TI - Regulation of lovastatin on a key inflammation-related microRNA in myocardial
cells.
AB - BACKGROUND: Advances in the understanding of cardiovascular pathogenesis have
highlighted that inflammation plays a central role in atherosclerotic coronary
heart disease. Therefore, exploring pharmacologically based anti-inflammatory
treatments to be used in cardiovascular therapeutics is worthwhile to promote the
discovery of novel ways of treating cardiovascular disorders. METHODS: The
myocardial cell line H9c2(2-1) was exposed to lipopolysaccharide (LPS) in culture
and resulted in a cellular pro-inflammation status. miR-21 microRNA levels were
detected using quantitative real-time polymerase chain reaction (Q-RT-PCR). The
influence of lovastatin on miR-21 under normal and pro-inflammatory conditions
was tested after being added to the cell culture mixture for 24 hours.
Conditional gene function of two predicted cardiovascular system relevant
downstream targets of miR-21, protein phosphatase 1 regulatory subunit 3A
(PPP1R3A) and signal transducer and activator of transcription 3 (STAT3), were
analyzed with immunoblotting. RESULTS: Forty-eight hours of LPS treatment
significantly increased the miR-21 to 170.71%+/- 34.32% of control levels (P =
0.002). Co-treatment with lovastatin for 24 hours before harvesting attenuated
the up-regulation of miR-21 (P = 0.013). Twenty-four hours of lovastatin exposure
up-regulated PPP1R3A to 143.85%+/- 21.89% of control levels in cardiomyocytes (P
= 0.023). Lovastatin up-regulated the phosphorylation level of STAT3 compared to
the background LPS pretreatment (P = 0.0077), this effect was significantly (P =
0.018) blunted when miR-21 was functionally inhibited. CONCLUSIONS: miR-21 plays
a major role in the regulation of the cellular anti-inflammation effects of
lovastatin.
PMID- 25131239
TI - Comparison of the clinical and radiological outcomes following midvastus and
medial parapatellar approaches for total knee arthroplasty: a meta-analysis.
AB - BACKGROUND: Controversy still exists regarding whether medial parapatellar
approach (MP) or midvastus approach (MV) is preferable in total knee arthroplasty
(TKA) up to now. The aim of this meta-analysis was to compare the clinical and
radiological outcomes following the MV or MP for TKA. METHODS: A comprehensive
search of unrestricted-language literature of all studies comparing MP with MV
was conducted through the electronic literature databases of PubMed, EMBASE,
Cochrane Library, CNKI, VIP, and WANFANG. Retrieval time was from the time when
databases were built to October 2013. Manual search of relevant trials, reviews,
and related articles was also performed. Outcomes of interest included
postoperative knee extensor and flexor function, postoperative pain, patella
tilt, and complications. Relative risk (RR) and weighted mean differences (WMD)
from each trial were pooled using random-effects or fixed-effects model depending
on the heterogeneity of the included studies. A subgroup analysis or a
sensitivity analysis was conducted to explore the potential source of
heterogeneity when necessary. RESULTS: Twenty-one randomized controlled trials
(RCTs) comprising 1 188 patients (1 450 knees) were eligible. Our results showed
that MV was associated with better early postoperative extension (WMD = -1.26,
95% CI -2.36 to -0.16, P = 0.02) and flexion (WMD = 10.13, 95% CI 5.36 to 14.90,
P < 0.01), less postoperative pain (WMD = -0.21, 95% CI -0.34 to -0.07, P =
0.002) , and no greater risk for complications than MP. The patella tilt did not
differ significantly between the two groups (WMD = -0.70, 95% CI -1.94 to 0.54, P
= 0.27). CONCLUSIONS: MV may be a better approach than MP, as it improves
postoperative early joint function and decreases pain. Future multi-center
randomized controlled studies with large sample sizes are required to verify the
current findings.
PMID- 25131240
TI - Prevalence of depression in coronary heart disease in China: a systematic review
and meta-analysis.
AB - BACKGROUND: Coronary heart diseases (CHD) have been identified as one of topmost
diseases affecting the Chinese population. However, depression in CHD has not
been reported and there are limited high quality empirical studies in China
focused on the prevalence of the comorbidity. This study aimed to estimate the
pooled prevalence of depression with CHD in China. METHODS: Systematic review and
meta-analysis of published epidemiologic studies on the depression in CHD
patients in China were conducted. The research findings dated before 30 September
2013 were obtained from Ovid Medline, EMBASE and two Chinese electronic
publication libraries WANFANG and CNKI. We used "cardiovascular disease",
"depression" and "China" as the search themes in Ovid Medline and EMBASE and
"cardiovascular disease" and "depression" in WANFANG and CNKI. Random-effects
meta-analysis was used to estimate the prevalence of depression in CHD patients.
RESULTS: Twenty-seven studies were included in the review. Twenty-three studies
had 5 236 participants who were hospitalized and four studies had 1 353
participants from community. The overall prevalence of depression in CHD from
hospital was 51% (95% CI: 0.43, 0.58; I-squared = 97%, P = 0.000).The prevalence
of depression in CHD from community ranged between 34.6% to 45.8%, and the severe
depression was found ranging between 3.1% to 11.2%. CONCLUSIONS: On comparing
data with other countries, the prevalence of depression in CHD among admitted
patients in China was found to be high. The physicians and healthcare providers
should pay more attention to the "physical-mental" health of the CHD patients.
PMID- 25131241
TI - Mixed phenotype acute leukemia.
AB - OBJECTIVE: To highlight the current understanding of mixed phenotype acute
leukemia (MPAL). DATA SOURCES: We collected the relevant articles in PubMed (from
1985 to present), using the terms "mixed phenotype acute leukemia", "hybrid acute
leukemia", "biphenotypic acute leukemia", and "mixed lineage leukemia". We also
collected the relevant studies in WanFang Data base (from 2000 to present), using
the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia". STUDY
SELECTION: We included all relevant studies concerning mixed phenotype acute
leukemia in English and Chinese version, with no limitation of research design.
The duplicated articles are excluded. RESULTS: MPAL is a rare subgroup of acute
leukemia which expresses the myeloid and lymphoid markers simultaneously. The
clinical manifestations of MPAL are similar to other acute leukemias. The World
Health Organization classification and the European Group for Immunological
classification of Leukaemias 1998 criteria are most widely used. MPAL does not
have a standard therapy regimen. Its treatment depends mostly on the patient's
unique immunophenotypic and cytogenetic features, and also the experience of
individual physician. The lack of effective treatment contributes to an
undesirable prognosis. CONCLUSION: Our understanding about MPAL is still limited.
The diagnostic criteria have not been unified. The treatment of MPAL remains to
be investigated. The prognostic factor is largely unclear yet. A better
diagnostic criteria and targeted therapeutics will improve the therapy effect and
a subsequently better prognosis.
PMID- 25131242
TI - Sphingosine Kinase-1/sphingosine 1-phosphate pathway in diabetic nephropathy.
AB - OBJECTIVE: Diabetic nephropathy (DN) is the major cause of end-stage renal
disease worldwide and its prevalence continues to increase. Currently, therapies
for DN provide only partial renoprotection; hence new targets for therapeutic
intervention need to be identified. In this review, we summarized the new target,
sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) pathway, explored its
potential therapeutic role in the prevention and treatment of DN. DATA SOURCES:
Most relevant articles were mainly identified by searching PubMed in English.
STUDY SELECTION: Mainly original articles and critical review articles by major
pioneer investigators in this field were selected to be reviewed. RESULTS:
SphK1/S1P pathway can be activated by hyperglycemia, advanced glycation end
products, and many pro-inflammatory cytokines, which leads to fibronectin,
transforming growth factor-beta1 up-regulation and AP-1 activation. And then it
could promote glomerular mesangial cells proliferation and extracellular matrix
accumulation, mediating the initiation and progression of diabetic renal
fibrosis. CONCLUSIONS: SphK1/S1P pathway is closely correlated with the
pathogenesis of DN. The results suggest that SphK1/S1P pathway as a new target
for clinically improving DN in future is of great prospect.
PMID- 25131243
TI - Cardiorenal syndrome: pathophysiological mechanism, preclinical models, novel
contributors and potential therapies.
AB - OBJECTIVE: To review the current knowledge about the pathophysiological
mechanisms, preclinical models, novel contributors and potential therapies of
cardiorenal syndrome. DATA SOURCES: The literature concerning cardiorenal
syndrome in this review was collected from PubMed published in English up to
January 2014. STUDY SELECTION: Original articles and critical reviews related to
cardiorenal syndrome were selected and carefully analyzed. RESULTS: Cardiorenal
syndrome is a condition characterized by kidney and heart failure where failure
of one organ worsens the function of the other thus further accelerating the
progressive failure of both organs. The pathophysiology of cardiorenal syndrome
is not fully understood, but may be caused by a complex combination of
neurohormonal system activation, endothelial dysfunction, proteinuria, oxidative
stress, uremic toxins and other factors. Managing cardiorenal syndrome is still a
major therapeutic challenge in clinical practice because many of the drugs used
to control heart failure can worsen renal function, and vice versa. Non
dialyzable uremic toxins, such as indoxyl sulfate, causing detrimental effects on
the heart and kidney as well as stimulation of inflammatory responses, may be an
effective therapeutic target for cardiorenal syndrome. CONCLUSIONS: Suitable
disease models of cardiorenal syndrome are urgently needed to investigate the
pathophysiology and effective therapeutic approaches to the condition. Non
dialyzable protein-bound uremic toxins that may have cardiac and renal effects
may provide therapeutic benefit to cardiorenal syndrome patients.
PMID- 25131244
TI - Predictors of anti-vascular endothelial growth factor treatment responses in
macular edema following central vein occlusion.
PMID- 25131245
TI - Neurological outcomes of patients admitted to the intensive care unit for cardiac
arrest.
PMID- 25131246
TI - Robotic and laparoscopic hybrid pancreaticoduodenectomy: surgical techniques and
early outcomes.
PMID- 25131247
TI - Pulmonary embolism with septicemia after N-butyl-2-cyanoacrylate injection for
bleeding gastric varices.
PMID- 25131248
TI - Extracorporeal membrane oxygenation as a platform for the management of massive
hemoptysis caused by bronchial artery aneurysm.
PMID- 25131249
TI - Aortic valve replacement for quadricuspid aortic valve with regurgitation and
stenosis in a renal transplant recipient.
PMID- 25131250
TI - Significance of ST-segment elevation in lead aVR.
PMID- 25131251
TI - Caseous calcification of the mitral annulus: a rare variant of mitral annular
calcification.
PMID- 25131252
TI - Weaning method from mechanical ventilation, more computer or clinical
perspective: who is helping whom truly?
PMID- 25131253
TI - Treatment of coexisting bullous pemphigoid and psoriasis with triptergium
wilfordii.
PMID- 25131254
TI - Ruptured pancreatic desmoid tumor presenting as hemorrhagic shock: a rare cause
of acute abdomen.
PMID- 25131255
TI - Should radioactive iodine therapy be administrated in patient of papillary
thyroid carcinoma?
PMID- 25131256
TI - Severity stratification of aplastic anemia.
PMID- 25131257
TI - Circulating miR-192 in liver fluke-associated cholangiocarcinoma patients: a
prospective prognostic indicator.
AB - BACKGROUND: This study aimed to investigate the miR-192 levels in patients' sera
of liver fluke-associated cholangiocarcinoma (CCA) for a prospective prognostic
indicator. METHODS: MicroRNA polymerase chain reaction (PCR) array was performed
using pooled serum samples from 11 CCA patients and nine healthy subjects.
Selected miRNAs were verified for the differential levels in both sera and tumor
tissues (of patients and Opisthorchis viverrini (Ov)-induced CCA model) using
TaqMan miRNA expression assay. RESULTS: Our results demonstrated that miR-192 was
significantly higher in the serum of CCA patients than that in healthy subjects
giving a sensitivity of 74% and specificity of 72% (area under the curve [AUC] =
0.803; 95% confidence interval [CI], 0.708-0.897, P < 0.0001). Serum miR-192
examined in Ov infected subjects and subjects with periductal fibrosis were
increased but not statistically significantly when compared with healthy
subjects. High levels of serum miR-192 were significantly correlated with lymph
node metastasis (P = 0.047) and shorter survival compared with individuals with
low levels of serum miR-192 (hazard ratio [HR] 2.076, 95% CI 1.004-4.291, P =
0.049). We also found that the expression levels of miR-192 appeared to be
elevated in both CCA tissues of patients and in Ov-induced CCA tissues of a
hamster model. CONCLUSIONS: This finding indicates that elevated levels of miR
192 may be involved in CCA genesis and have a potential utility as a noninvasive
prognostic indicator for CCA patients.
PMID- 25131258
TI - Influence of cultivar and ripening time on bioactive compounds and antioxidant
properties in Cape gooseberry (Physalis peruviana L.).
AB - BACKGROUND: Cape gooseberry (Physalis peruviana) is an exotic fruit highly valued
for its organoleptic properties and bioactive compounds. Considering that the
presence of phenolics and ascorbic acid could contribute to its functional
capacity, it is important to investigate the quality parameters, bioactive
contents and functional properties with respect to genotype and ripening time. In
this study the genotype effect was evaluated in 15 cultivars for two different
harvest times. Changes during maturation were recorded in two commercial
cultivars within seven levels of maturity. RESULTS: Multivariate statistical
analysis suggested that phenolic content and ORAC value were mainly affected by
harvest time and that ascorbic acid content and DPPH level were mainly affected
by genotype. In addition, acidity, phenolic content, ORAC value and inhibition of
LDL oxidation decreased with maturity, but soluble solids content, ascorbic acid
content, beta-carotene content and DPPH-scavenging activity were higher in mature
fruits. CONCLUSION: The phenolic content, ascorbic acid content and antioxidant
properties of Cape gooseberry fruit were strongly affected by cultivar, harvest
time and maturity state. Consequently, the harvest time must be scheduled
carefully to gain the highest proportion of bioactive compounds according to the
specific cultivar and the environment where it is grown.
PMID- 25131259
TI - Solvent induced helical aggregation in the self-assembly of cholesterol tailed
platinum complexes.
AB - Three alkynylplatinum(ii) bipyridyl complexes in which two cholesterol groups are
combined with a bipyridyl group via alkyl chains and amido bonds were designed
and synthesized. The complexes have different lengths of ethylene glycol chains
at the para-position of 1-phenylethyne. All three complexes can self-assemble to
gel networks in DMSO, while only the morphology of 1a without an ether chain
shows a well-defined right-handed helical structure in layer packing mode.
However, 1c with long ethylene glycol chains forms perfect regular left-handed
helical structures in aqueous ethanol solution while the volume percentage of
water is less than 5% (v/v). As the ratio of water increases, the chirality
changes from a left-handed helix to a right-handed helix and the packing mode
alters from a monolayer structure to a hexagonal structure. As the ratio of water
further increases to greater than 50% (v/v), the structure of the assembly
finally transforms into bilayer vesicles. The process of the morphology
transition is traced by circular dichroism spectra, powder X-ray diffraction, SEM
and TEM images. The result indicates that a polar solvent (water) acts as a
trigger to change the self-assembly of the chiral structures of the complex due
to the strong hydrophobic interaction between cholesterol groups and the balance
of the hydrophobicity and hydrophilicity of the solvent environment.
PMID- 25131260
TI - The small GTPases regulate HMC05-induced NQO-1 expression with an antioxidant
effect in smooth muscle cells.
AB - Recently, Banhabackchulchunmatang (HMC05) has been implicated as a preventive
and/or therapeutic candidate for cardiovascular diseases due to its inhibition of
atherosclerosis lesions and its reduction of neointima formation. Knowledge of
the mechanism of HMC05 in smooth muscle cells (SMC) is limited. However, SMC may
be a potential target for HMC05 therapy because they are supported by the HMC05
mediated preservation of medial smooth muscle cell layers in pathogenic
progression. Therefore, in the present study, we hypothesized that the effect of
HMC05 is associated with reduced nicotinamide adenine dinucleotide phosphate
(NAD(P)H):quinone oxidoreductase-1 (NQO-1) gene regulation, which precipitates an
antioxidant effect in SMC. HMC05 significantly increased NQO-1 gene expression in
a dose- and time-dependent manner. The reactive oxygen species-mediated toxicity
that was generated by xanthine/xanthine oxidase was suppressed by HMC05. The
knockdown of the NQO-1 gene abrogated the HMC05-mediated cytoprotection.
Interestingly, pretreatment with a chemical inhibitor of geranylgeranyl
transferase 1 or farnesyl transferase abolished the NQO-1 gene induction and
cytoprotection by HMC05. The transfection of dominant negative RhoA or Ras
suppressed HMC05-induced gene expression. Berberine and hesperidin, which are
found in large quantities in HMC05, also induced NQO-1 gene expression. Taken
together, this is the first study to demonstrate that HMC05 is efficacious in
protection against oxidative stress through NOQ-1 gene induction via the
regulation of RhoA and/or Ras, and that berberine and hesperidin are major
components of NQO-1 gene induction. This study provides mechanistic targets of
HMC05 in reducing atherosclerotic lesions in atherosclerosis.
PMID- 25131261
TI - Thyroarytenoid cross-innervation by the external branch of the superior laryngeal
nerve in the porcine model.
AB - OBJECTIVES/HYPOTHESIS: Cross-innervation patterns to the thyroarytenoid (TA)
muscle have long been sought after. We have identified in the porcine model,
cross-innervation by way of the external branch of the superior laryngeal nerve
(eSLN). STUDY DESIGN: Experimental study. METHODS: TA contraction was
electromyographically recorded when electrically stimulating the eSLN in six
porcine necks. The recurrent laryngeal nerve (RLN) was subsequently transected.
The insertion of the cricothyroid (CT) muscle on the cricoid was then
subsequently removed as well. RESULTS: Stimulation of the eSLN rendered a
response from the TA muscle in 6/6 subject necks, with a mean latency of 2.76
msec. TA muscle contraction by way of eSLN stimulation persisted after the RLN
was transected and after CT insertion release. CONCLUSIONS: The TA muscle is
directly cross-innervated by a branch of the eSLN in the porcine model. This
finding may have implications regarding possible future laryngeal pacing
strategies and could be a target nerve for rehabilitation.
PMID- 25131263
TI - Do the treasures of 'big data' combined with behavioural intervention therapies
contain the key to the mystery of large psychiatric issues?
PMID- 25131262
TI - Association of daunorubicin to a lipid nanoemulsion that binds to low-density
lipoprotein receptors enhances the antitumour action and decreases the toxicity
of the drug in melanoma-bearing mice.
AB - OBJECTIVES: To test the toxicity and antitumoral activity of the compound N-oleyl
daunorubicin (oDNR) with a cholesterol-rich nanoemulsion (LDE) formulation.
METHODS: LDE-oDNR was prepared by high-pressure homogenisation of lipid mixtures.
B16F10 melanoma cells and NIH/3T3 fibroblasts were used for cytotoxicity tests.
The maximum tolerated dose (MTD) of both commercial and LDE-oDNR was determined
in mice, and melanoma-bearing mice were used for the antitumoral activity tests.
KEY FINDINGS: CC50 for LDE-oDNR and DNR in melanoma cells were 200 MUm and 15
MUm, respectively, but LDE-oDNR was less toxic against fibroblasts than DNR. MTD
for LDE-oDNR was 65-fold higher than commercial DNR. In tumour-bearing mice, LDE
oDNR (7.5 MUmol/kg) reduced tumour growth by 59 +/- 2%, whereas the reduction by
DNR was only 23 +/- 2%. LDE-oDNR increased survival rates (P < 0.05), which was
not achieved by DNR treatment. The number of mice with metastasis was only 30% in
LDE-oDNR-treated mice, compared with 82% under DNR treatment. By flow cytometry,
there were 9% viable cells in tumours of animals treated with LDE-oDNR compared
with 27% in DNR-treated animals. Less haematological toxicity was observed in LDE
oDNR-treated mice. CONCLUSIONS: Compared with DNR, LDE-oDNR improved tumour
growth inhibition and survival rates with pronouncedly less toxicity, and thus
may become a new tool for cancer treatment.
PMID- 25131264
TI - Repeated formaldehyde inhalation impaired olfactory function and changed SNAP25
proteins in olfactory bulb.
AB - BACKGROUND: Formaldehyde inhalation exposure, which can occur through
occupational exposure, can lead to sensory irritation, neurotoxicity, mood
disorders, and learning and memory impairment. However, its influence on
olfactory function is unclear. OBJECTIVES: To investigate the mechanism and the
effect of repeated formaldehyde inhalation exposure on olfactory function.
METHODS: Rats were treated with formaldehyde inhalation (13.5+/-1.5 ppm, twice 30
minutes/day) for 14 days. Buried food pellet and locomotive activity tests were
used to detect olfactory function and locomotion. Western blots were used to
evaluate synaptosomal-associated protein 25 (SNAP25) protein levels in the
olfactory bulb (OB) lysate and synaptosome, as well as mature and immature
olfactory sensory neuron markers, olfactory marker protein (OMP), and Tuj-1. Real
time polymerase chain reaction (PCR) was used to detect SNAP25 mRNA amounts.
RESULTS: Repeated formaldehyde inhalation exposure impaired olfactory function,
whereas locomotive activities were unaffected. SNAP25 protein decreased
significantly in the OB, but not in the occipital lobe. SNAP25 also decreased in
the OB synaptosome when synaptophysin did not change after formaldehyde
treatment. mRNA levels of SNAP25A and SNAP25B were unaffected. Mature and
immature olfactory sensory neuron marker, OMP, and Tuj-1, did not change after
formaldehyde treatment. CONCLUSION: Repeated formaldehyde exposure impaired
olfactory function by disturbing SNAP25 protein in the OB.
PMID- 25131268
TI - Seventy-five years completed and thirty-six to go!
PMID- 25131265
TI - Uses of cancer registries for public health and clinical research in Europe:
Results of the European Network of Cancer Registries survey among 161 population
based cancer registries during 2010-2012.
AB - AIM: To provide insight into cancer registration coverage, data access and use in
Europe. This contributes to data and infrastructure harmonisation and will foster
a more prominent role of cancer registries (CRs) within public health, clinical
policy and cancer research, whether within or outside the European Research Area.
METHODS: During 2010-12 an extensive survey of cancer registration practices and
data use was conducted among 161 population-based CRs across Europe. Responding
registries (66%) operated in 33 countries, including 23 with national coverage.
RESULTS: Population-based oncological surveillance started during the 1940-50s in
the northwest of Europe and from the 1970s to 1990s in other regions. The
European Union (EU) protection regulations affected data access, especially in
Germany and France, but less in the Netherlands or Belgium. Regular reports were
produced by CRs on incidence rates (95%), survival (60%) and stage for selected
tumours (80%). Evaluation of cancer control and quality of care remained modest
except in a few dedicated CRs. Variables evaluated were support of clinical
audits, monitoring adherence to clinical guidelines, improvement of cancer care
and evaluation of mass cancer screening. Evaluation of diagnostic imaging tools
was only occasional. CONCLUSION: Most population-based CRs are well equipped for
strengthening cancer surveillance across Europe. Data quality and intensity of
use depend on the role the cancer registry plays in the politico, oncomedical and
public health setting within the country. Standard registration methodology could
therefore not be translated to equivalent advances in cancer prevention and mass
screening, quality of care, translational research of prognosis and survivorship
across Europe. Further European collaboration remains essential to ensure access
to data and comparability of the results.
PMID- 25131266
TI - Surgical site infection after total en bloc spondylectomy: risk factors and the
preventive new technology.
AB - BACKGROUND CONTEXT: Surgical site infection (SSI) associated with instruments
remains a serious and common complication in patients who undergo total en bloc
spondylectomy (TES). It is very important that the risk factors for SSI are known
to prevent it. PURPOSE: The purpose of the study was to identify independent risk
factors for SSI after TES and evaluate the positive effect of iodine-supported
spinal instruments in the prevention of SSI after TES. STUDY DESIGN: This is a
retrospective clinical study. PATIENT SAMPLE: One hundred twenty-five patients
who underwent TES for vertebral tumor were evaluated. OUTCOME MEASURES: Incidence
rate of SSI, risk factors for SSI after TES, and safety of iodine-supported
spinal instruments were the outcome measures. METHODS: Risk factors for SSI were
analyzed using logistic regression. In recent 69 patients with iodine-supported
spinal instruments, the thyroid hormone levels in the blood were examined to
confirm if iodine from the implant influenced thyroid function. Postoperative
radiological evaluations were performed regularly. RESULTS: The rate of SSI was
6.4% (8/125 patients). By multivariate logistic regression, combined anterior and
posterior approach and nonuse of iodine-supported spinal instruments were
associated with an increased risk of SSI. The rate of SSI without iodine
supported spinal instruments was 12.5%, whereas the rate with iodine-supported
spinal instruments was 1.4%. This difference was statistically significant. There
were no detected abnormalities of thyroid gland function with the use of iodine
supported instruments. Among the 69 patients with iodine-supported spinal
instruments, 2 patients required additional surgery because of instrument
failure. However, there were no obvious involvements with the use of iodine
supported spinal instruments. CONCLUSIONS: This study identified combined
anterior and posterior approach and nonuse of iodine-supported spinal instruments
to be independent risk factors for SSI after TES. Iodine-supported spinal
instrument was extremely effective for prevention of SSI in patients with
compromised status, and it had no detection of cytotoxic or adverse effects on
the patients.
PMID- 25131271
TI - Third-grade retention and reading achievement in Texas: a nine year panel study.
AB - The academic performance of over 38,000 Texas students who failed the state's
1994 reading test was examined through their sophomore year in high school.
Propensity score matching resulted in strata with retained and promoted students
of comparable observed characteristics. Reading scores were analyzed using a two
level hierarchical linear model. Same grade comparisons show that third graders
failing the state-mandated reading test who repeated the grade consistently
outperformed in later grades the socially promoted children who also failed the
third grade test. Additional analyses indicate that alternative explanations for
the findings such as omitted variables, regression to the mean, differential
panel attrition and cohort effects are not supported. The results are consistent
with findings from other recent studies which suggest that grade retention in
third grade may help increase student achievement.
PMID- 25131270
TI - A neural mass model based on single cell dynamics to model pathophysiology.
AB - Neural mass models are successful in modeling brain rhythms as observed in
macroscopic measurements such as the electroencephalogram (EEG). While the
synaptic current is explicitly modeled in current models, the single cell
electrophysiology is not taken into account. To allow for investigations of the
effects of channel pathologies, channel blockers and ion concentrations on
macroscopic activity, we formulate neural mass equations explicitly incorporating
the single cell dynamics by using a bottom-up approach. The mean and variance of
the firing rate and synaptic input distributions are modeled. The firing rate
curve (F(I)-curve) is used as link between the single cell and macroscopic
dynamics. We show that this model accurately reproduces the behavior of two
populations of synaptically connected Hodgkin-Huxley neurons, also in non-steady
state.
PMID- 25131272
TI - Understanding the links between education and smoking.
AB - This study extends the theoretical and empirical literature on the relationship
between education and smoking by focusing on the life course links between
experiences from adolescence and health outcomes in adulthood. Differences in
smoking by completed education are apparent at ages 12-18, long before that
education is acquired. I use characteristics from the teenage years, including
social networks, future expectations, and school experiences measured before the
start of smoking regularly to predict smoking in adulthood. Results show that
school policies, peers, and youths' mortality expectations predict smoking in
adulthood but that college aspirations and analytical skills do not. I also show
that smoking status at age 16 predicts both completed education and adult
smoking, controlling for an extensive set of covariates. Overall, educational
inequalities in smoking are better understood as a bundling of advantageous
statuses that develops in childhood, rather than the effect of education
producing better health.
PMID- 25131273
TI - Tracing the cigarette epidemic: an age-period-cohort study of education, gender
and smoking using a pseudo-panel approach.
AB - This study examined if temporal variations in daily cigarette smoking and never
smoking among groups with different levels of education fit the pattern proposed
by the theory of diffusion of innovations (TDI), while taking into account the
separate effects of age, period and birth cohort (APC). Aggregated data from
nationally representative interview surveys from Norway from 1976 to 2010 was
used to calculate probabilities of smoking using an APC approach in which the
period variable was normalized to pick up short term cyclical effects. Results
showed that educational differences in smoking over time were more strongly
determined by birth cohort membership than variations in smoking behavior across
the life course. The probability of daily smoking decreased faster across cohorts
among higher compared to lower educated. In contrast, the change in probability
of never having smoked across cohorts was similar in the two education groups,
but stronger among men compared to women. Moreover, educational differences in
both daily and never smoking increased among early cohorts and leveled off among
late cohorts. The results emphasizes the importance of birth cohort for social
change and are consistent with TDI, which posits that smoking behavior diffuse
through the social structure over time.
PMID- 25131274
TI - Life satisfaction across nations: the effects of women's political status and
public priorities.
AB - Feminist scholars suggest that improving the quality of life of individuals
living in nations around the world may be more readily achieved by increasing
women's political power and by reorienting public-policy priorities, than by
focusing primarily on economic growth. These considerations raise the question of
which characteristics of societies are associated with the quality of life of the
people in those societies. Here, we address this issue empirically by
statistically analyzing cross-national data. We assess the effects of gender
equality in the political sphere, as well as a variety of other factors, on the
subjective well-being of nations, as indicated by average self-reported levels of
life satisfaction. We find that people report the highest levels of life
satisfaction in nations where women have greater political representation, where
military spending is low, and where health care spending is high, controlling for
a variety of other factors. GDP per capita, urbanization, and natural resource
exploitation are not clearly associated with life satisfaction. These findings
suggest that nations may be able to improve the subjective quality of life of
people without increasing material wealth or natural resource consumption by
increasing gender equality in politics and changing public spending priorities.
PMID- 25131275
TI - Is the social volcano still dormant? Trends in Chinese attitudes toward
inequality.
AB - Data from two China national surveys, in 2004 and 2009, focusing on popular
attitudes toward current inequalities and mobility opportunities, are compared to
examine two key questions: (1) Did the continued rise in income gaps and the
impact within China of the global financial crisis lead to rising popular anger
about the unfairness of current inequality patterns in 2009? and (2) Did the
social contours of attitudes toward current inequalities shift over the five
years between surveys? Through systematic comparisons of data from both surveys,
we conclude that there is no general increase in anger about inequalities in the
2009 survey, and that the predictors of variations in these attitudes had changed
relatively little, with the unexpectedly positive views of villagers still
visible in 2009, although a bit muted. Trends in Chinese society between 2004 and
2009, and in the personal experience of survey respondents, are used to explain
why popular acceptance of current inequalities remains widespread, despite
continuing increases in China's income gaps.
PMID- 25131277
TI - Social welfare support and homicide: longitudinal analyses of European countries
from 1994 to 2010.
AB - The purpose of this research is to explore the extent to which retrenchment in
welfare support is related to homicide trends across European countries between
1994 and 2010. Using a longitudinal decomposition design that allows for stronger
causal inferences compared to typical cross-sectional designs, we examine these
potential linkages between social support spending and homicide with data
collected from a heterogeneous sample of European nations, including twenty
Western nations and nine less frequently analyzed East-Central nations, during
recent years in which European nations generally witnessed substantial changes in
homicide rates as well as both economic prosperity and fiscal crisis. Results
suggest that even incremental, short-term changes in welfare support spending are
associated with short-term reductions in homicide-specifically, impacting
homicide rates within two to three years for this sample of European nations.
PMID- 25131276
TI - Intimate partner victimization, poor relationship quality, and depressive
symptoms during young adulthood.
AB - Using longitudinal data from the Toledo Adolescent Relationships Study (n = 927),
we examined physical victimization, poor quality, and depression among young
adults in casually dating, exclusively dating, cohabiting, and marital
relationships. In multivariate models, victimization was a risk factor for
depression with the inclusion of prior depression, family factors reflecting the
intergenerational transmission of violence, sociodemographic background, and
relationship characteristics including union status. With the inclusion of
indicators of poor relational quality, victimization was not a significant
predictor of depression. Arguing and poor communication influenced victimization
and depression. Associations between victimization and depression did not differ
by gender, nor were the effects of poor quality on depression conditional on
gender. Thus, victimization occurs within relationships characterized by a range
of negative dynamics. Multifaceted relationship-centered prevention efforts are
more useful than focusing only on the use of aggression with a partner.
PMID- 25131278
TI - Homonegativity among first and second generation migrants in Europe: the
interplay of time trends, origin, destination and religion.
AB - Previous studies reported declining disapproval of homosexuality in Europe but
have simultaneously identified the decelerating effect of religiosity and the
higher disapproval of homosexuality among migrants. In this paper, we address
disapproval of homosexuality among first- and second-generation migrants in
Europe by assessing (1) period and cohort changes, (2) origin and destination
country influences and (3) the role of religiosity. We develop a specific cross
classified multilevel design enabling us to simultaneously examine these
influences. We test hypotheses using a subsample of the European Social Survey
(ESS), containing 19,878 first and second generation migrants. The analyses lead
to three important conclusions. Firstly, disapproval of homosexuality is
declining both over time and across cohorts. Secondly, migrants conform to levels
of disapproval of homosexuality among natives in the destination country, and
this explains the decline among migrants over time. Thirdly, religion has a multi
faceted influence on levels of disapproval of homosexuality among migrants.
PMID- 25131279
TI - College quality and hourly wages: evidence from the self-revelation model,
sibling models and instrumental variables.
AB - This paper addresses the recent discussion on confounding in the returns to
college quality literature using the Norwegian case. The main advantage of
studying Norway is the quality of the data. Norwegian administrative data provide
information on college applications, family relations and a rich set of control
variables for all Norwegian citizens applying to college between 1997 and 2004 (N
= 141,319) and their succeeding wages between 2003 and 2010 (676,079 person-year
observations). With these data, this paper uses a subset of the models that have
rendered mixed findings in the literature in order to investigate to what extent
confounding biases the returns to college quality. I compare estimates obtained
using standard regression models to estimates obtained using the self-revelation
model of Dale and Krueger (2002), a sibling fixed effects model and the
instrumental variable model used by Long (2008). Using these methods, I
consistently find increasing returns to college quality over the course of
students' work careers, with positive returns only later in students' work
careers. I conclude that the standard regression estimate provides a reasonable
estimate of the returns to college quality.
PMID- 25131280
TI - Identifying predictors of survey mode preference.
AB - To increase the likelihood of response, many survey organizations attempt to
provide sample members with a mode they are thought to prefer. Mode assignment is
typically based on conventional wisdom or results from mode choice studies that
presented only limited options. In this paper we draw heavily on research and
theory from the mode effects and the survey participation literatures to develop
a framework for understanding what characteristics should predict mode
preferences. We then test these characteristics using data from two different
surveys. We find that measures of familiarity with and access to a mode are the
strongest predictors of mode preference and measures of safety concerns, physical
abilities, and normative concerns are unexpectedly weak predictors. Our findings
suggest that variables that may exist on sample frames can be used to inform the
assignment of "preferred" modes to sample members.
PMID- 25131281
TI - Abortion attitudes in context: a multidimensional vignette approach.
AB - The effects of relationship status, rationale for considering abortion (life
circumstance versus health issue), and the male partner's wishes on abortion
attitudes were examined using a multiple-segment factorial vignette with a
probability sample of 532 Kentucky households. Respondents expressed strong
opinions in the absence of contextual details, yet many shifted the direction of
their strongly-held positions once contextual information was revealed that
challenged their initial assumptions. Results confirm and extend prior research
by indicating that attitudes are strongly held but are simultaneously highly
responsive to context. The validity of surveys and polls that attempt to measure
global attitudes toward abortion, such as pro-choice versus pro-life, in the
absence of contextual details is therefore questioned. The full context of one's
life and situation is weighed in the abortion decision-making process, and our
findings indicate that attitudes toward abortion are largely responsive and
reflective of that context as well.
PMID- 25131282
TI - Intelligence and childlessness.
AB - Demographers debate why people have children in advanced industrial societies
where children are net economic costs. From an evolutionary perspective, however,
the important question is why some individuals choose not to have children.
Recent theoretical developments in evolutionary psychology suggest that more
intelligent individuals may be more likely to prefer to remain childless than
less intelligent individuals. Analyses of the National Child Development Study
show that more intelligent men and women express preference to remain childless
early in their reproductive careers, but only more intelligent women (not more
intelligent men) are more likely to remain childless by the end of their
reproductive careers. Controlling for education and earnings does not at all
attenuate the association between childhood general intelligence and lifetime
childlessness among women. One-standard-deviation increase in childhood general
intelligence (15 IQ points) decreases women's odds of parenthood by 21-25%.
Because women have a greater impact on the average intelligence of future
generations, the dysgenic fertility among women is predicted to lead to a decline
in the average intelligence of the population in advanced industrial nations.
PMID- 25131283
TI - When do doctors follow patients' orders? Organizational mechanisms of physician
influence.
AB - Physicians, like other professionals, are expected to draw from specialized
knowledge while remaining receptive to clients' requests. Using nationally
representative U.S. survey data from the Community Tracking Study, this paper
examines the degree to which physicians are influenced by patients' requests, and
how physicians' workplaces may mediate acquiescence rates through three
mechanisms: constraints, protection, and incentives. We find that, based on
physicians' reports of their responses to patients' suggestions, patient
influence is rare. This influence is least likely to be felt in large workplaces,
such as large private practices, hospitals, and medical schools. We find that the
protection and incentives mechanisms mediate the relationship between workplace
types and physician acquiescence but more prescriptive measures such as
guidelines and formularies do not affect acquiescence. We discuss these findings
in light of the ongoing changes in the structure of medicine.
PMID- 25131284
TI - NIMBYism - a re-examination of the phenomenon.
AB - NIMBYism is the idea that citizens will oppose the siting of facilities in their
neighborhood for selfish reasons. Using a new treatment - type of facility rather
than geographical proximity to a particular site - the paper explores two rarely
researched manifestations of NIMBYism: that people are so sensitive to nuisances
that they oppose the siting of all facility types in their neighborhood; and that
people will adjust motivations for resistance to appear public minded. Results
from both observational and experimental studies support the basic claims of
NIMBYism.
PMID- 25131285
TI - The consequences of unrealized occupational goals in the transition to adulthood.
AB - Do unmet occupational goals have negative consequences for well-being? Several
social-psychological theories posit that aspirations become standards against
which individuals judge themselves, thereby decreasing well-being when unmet. Yet
other evidence points to young adults' goal flexibility and resilience,
suggesting unmet aspirations may not affect well-being. This paper tests these
alternatives using data from the National Longitudinal Study of Youth 1979 (N =
9016) and the National Educational Longitudinal Study of 1988 (N = 10,547) to
examine whether the degree of match between adolescent occupational aspirations
(NLSY) and expectations (NELS) and later attainment affect job satisfaction and
depression. This paper also examines gender differences in the cost to unmet
goals. Findings reveal a cost to falling short of one's occupational goals,
manifested in more depressive symptoms for men in the older cohort, and lower job
satisfaction for both men and women across two cohorts born approximately 14
years apart.
PMID- 25131286
TI - The misunderstood consequences of Shelley v. Kraemer.
AB - Shelley v. Kraemer (1948) was a landmark civil rights ruling, in which the
Supreme Court held that private racial covenants could not be enforced by the
state to evict black buyers of "restricted" homes. Fair housing scholars have
generally dismissed or downplayed the practical effects of Shelley, since other
forms of housing discrimination remained very powerful. Using spatial lag models
and detailed geographic data on the location of covenants and patterns of intra
urban black migration, we compare the role of Shelley with other forces shaping
mid-century neighborhood change. We find that Shelley precipitated white-to-black
neighborhood transitions after 1948 and changed the nature of the dual housing
market in important ways. We also show that increased black mobility produced a
sharp increase in intra-black economic segregation during the 1950s and 1960s.
PMID- 25131287
TI - Friendship networks and the social structure of opportunities for contact and
interaction.
AB - This paper explores the Partnermarktsurvey to analyze how the size and
composition of individuals' friendship networks are associated with the
opportunities for contact and interaction provided by individuals' immediate
social environment. The size and composition of individuals' social environment
are strongly reflected in the size and composition of their network of friends.
Several properties of an individual's foci of activity help to transform mere
contacts into opportunities for interaction. The paper suggests to combine macro
structural theory with micro-sociological theories about action and social
capital.
PMID- 25131288
TI - Political polarization on support for government spending on environmental
protection in the USA, 1974-2012.
AB - Since the early 1990s, the American conservative movement has become increasingly
hostile toward environmental protection and Congressional Republicans have become
increasingly anti-environmental in their voting records. Party sorting theory
holds that such political polarization among elites will likely extend to the
general public. Analyzing General Social Survey data from 1974 to 2012, we
examine whether political polarization has occurred on support for government
spending on environmental protection over this time period in the US general
public. We find that there has been significant partisan and ideological
polarization on support for environmental spending since 1992-consistent with the
expectations of party sorting theory. This political polarization on
environmental concern in the general public will likely endure save for political
convergence on environmental concern among elites in the near future. Such
polarization likely will inhibit the further development and implementation of
environmental policy and the diffusion of environmentally friendly behaviors.
PMID- 25131289
TI - The dynamic relationships between union dissolution and women's employment: a
life-history analysis of 16 countries.
AB - The specialization theory from Gary Becker is often used to explain the effect of
women's work on the risk of divorce. The main argument is that women with little
work experience have higher economic costs to exit marriage. Using the Fertility
and Family Surveys, we test for 16 countries to what extent women's employment
increases the risk of separation. We also more directly examine the role of
economic exit costs in separation by investigating the effect of separated
women's work history during the union on women's post-separation employment. The
results imply that Becker was right to some extent, especially in contexts with
little female employment support. However, in settings where women's employment
opportunities are more ample, sociological or psychological theories have
probably more explanatory power to explain the causes and consequences of union
dissolution.
PMID- 25131290
TI - Predictors of self-protective behaviors in non-sexual violent encounters: the
role of victim sex in understanding resistance.
AB - Self-protective behaviors are actions that victims take in a violent encounter to
thwart the attack or avoid/minimize injury. This study examines the predictors of
self-protective behaviors in non-sexual assault incidents with a particular focus
on how the sex of the victim may moderate these conclusions. Non-sexual assault
incidents in the National Crime Victimization Survey were analyzed (n=16,309) and
four categories of self-protective behaviors were regressed on a variety of
predictors using multivariate probit models. A variety of pre-assault factors
(e.g., demographic characteristics), situational characteristics (e.g., location
of assault), and the relationship between the victim and offender are associated
with the use of resistance. Situational characteristics emerged as the most
consistent and strongest predictors of self-protective behaviors. There was
little evidence to suggest that separate models for male and female victims were
warranted.
PMID- 25131291
TI - Twelve-year survey (2001-2012) of the antimicrobial susceptibility of
Streptococcus pneumoniae isolates from otorhinolaryngology clinics in Miyagi
Prefecture, Japan.
AB - INTRODUCTION: Streptococcus pneumoniae is one of the most common bacteria causing
otorhinolaryngological infections, such as acute otitis media and upper
respiratory tract infection. Our group surveyed the drug susceptibility profile
of S. pneumoniae isolates from otorhinolaryngology patients. MATERIALS AND
METHODS: A total of 41,069 S. pneumoniae isolates were detected at Miyagi Medical
Association Health Center between May 2001 and December 2012. Specimens were
obtained from patients at 40 otorhinolaryngology outpatient clinics in Miyagi
Prefecture, Japan. The minimum inhibitory concentrations (MICs) of 8
antimicrobial agents were measured using the broth microdilution method according
to Clinical and Laboratory Standards Institute guidelines. RESULTS: In children
aged 0-2 years old, the MIC50 values of penicillins decreased after 2010 (PCG: 1
MUg/ml (2010) to 0.06 MUg/ml (2012); ABPC: 1 MUg/ml (2010) to 0.25 MUg/ml
(2012)). The prevalence of penicillin-resistant S. pneumoniae (PRSP) decreased
from 35.2% (2010) to 14.6% (2012) in rhinorrhea specimens and from 43.4% (2010)
to 14.3% (2012) in otorrhea specimens. Susceptibility to cephems (ceftriaxone and
cefditoren) and carbapenems (panipenem) also showed improvement after 2010. For
macrolides (clarithromycin) and lincosamides (clindamycin), MIC50 values
increased in all age groups during the study period, and a high level of
resistance was seen until 2012. There were no marked changes of susceptibility to
fluoroquinolones (LVFX) during the study period. CONCLUSION: Improvement of
susceptibility of S. pneumoniae to beta-lactams occurred after 2010 in Miyagi
Prefecture, Japan.
PMID- 25131292
TI - Post-marketing safety and effectiveness evaluation of the intravenous anti
influenza neuraminidase inhibitor peramivir (I): a drug use investigation.
AB - Peramivir is the only intravenous formulation among anti-influenza neuraminidase
inhibitors currently available. Peramivir was approved for manufacturing and
marketing in Japan in January 2010. We conducted a drug use investigation of
peramivir from October 2010 to February 2012 and evaluated its safety and
effectiveness under routine clinical settings. We collected data of 1309 patients
from 189 facilities across Japan and examined safety in 1174 patients and
effectiveness in 1158 patients. In total, 143 adverse events were observed with
an incidence rate of 7.33% (86/1174). Of these, 78 events were adverse drug
reactions (ADRs) with an incidence rate of 4.34% (51/1174). The most frequently
reported ADRs were diarrhea, vomiting, and nausea, with incidence rates of 1.87%
(22/1174), 0.85% (10/1174), and 0.68% (8/1174), respectively. Moreover, no ADR
was reported as serious. ADR onset was within 3 days after the start of peramivir
administration in 91.0% (71 events) of the 78 ADRs, and ADRs were resolved or
improved within 7 days after onset in 96.2% (75 events) of the 78 ADRs. Neither
patient characteristics nor treatment factors appeared to significantly affect
drug safety. With regard to effectiveness, the median time to alleviation of both
influenza symptoms and fever was 3 days, including the first day of
administration. The present study demonstrates the safety and effectiveness of
peramivir under routine clinical settings.
PMID- 25131293
TI - Helicobacter cinaedi kidney cyst infection and bacteremia in a patient with
autosomal dominant polycystic kidney disease.
AB - A 48-year-old man with autosomal dominant polycystic kidney disease (ADPKD) was
admitted to our hospital with a 5-day history of lower right back pain, high
grade fever, and arthralgia. He was diagnosed with right kidney cyst infection
and bacteremia due to Helicobacter cinaedi (H. cinaedi) based on these symptoms,
highly elevated CRP (32.25 mg/dL), abdominal magnetic resonance imaging findings,
and the identification of H. cinaedi from blood cultures using PCR and sequence
analysis of the 16S ribosomal DNA gene. Intravenous cefotaxime 0.5 g twice daily
followed by meropenem 0.5 g twice daily and ciprofloxacin 200 mg twice daily were
partially effective; oral doxycycline added at 200 mg/day finally eradicated the
infection. Total duration of antimicrobial therapy was 9 weeks. H. cinaedi
infections typically present as bacteremia with or without cellulitis in
immunocompromised patients such as those with AIDS or malignant disease. To our
knowledge, this is the first report describing an ADPKD patient with H. cinaedi
cyst infection. Although H. cinaedi infections are increasingly recognized, even
in immunocompetent subjects, numerous cases may still be overlooked given that
this bacterium is slow-growing, and is difficult to culture, be Gram-stained, and
identify on phenotypic tests. Consideration of this bacterium as a possible
pathogen and sufficient duration of incubation with molecular testing are
necessary in treating ADPKD patients with cyst infection.
PMID- 25131294
TI - First report of spondylodiscitis due to vancomycin heteroresistant Staphylococcus
capitis in immunocompetent host.
AB - We report a successfully treated case of spondylodiscitis and bloodstream
infection due to vancomycin heteroresistant Staphylococcus capitis, in an adult
immunocompetent patient with multiple antibiotics intolerance. S. capitis is
rarely involved in osteomyelitis and, to our knowledge, this is the first report
of vancomycin heteroresistance phenomenon in an S. capitis strain causing
spondylodiscitis.
PMID- 25131295
TI - Two types of genetic carrier, the IncP genomic island and the novel IncP-1beta
plasmid, for the aac(2')-IIa gene that confers kasugamycin resistance in
Acidovorax avenae ssp. avenae.
AB - A unique aminoglycoside antibiotic, kasugamycin (KSM), has been used to control
many plant bacterial and fungal diseases in several countries. The emergence of
KSM-resistant Acidovorax avenae ssp. avenae and Burkholderia glumae, which cause
rice bacterial brown stripe and rice bacterial grain and seedling rot,
respectively, is a serious threat for the effective control of these diseases.
Previously, we have identified the aac(2')-IIa gene, encoding a KSM 2'-N
acetyltransferase, from both KSM-resistant pathogens. Although all KSM-resistant
isolates from both species possess the aac(2')-IIa gene, only A. avenae strain 83
showed higher resistance than other strains. In this research, kinetic analysis
indicates that an amino acid substitution from serine to threonine at position
146 of AAC(2')-IIa in strain 83 is not involved in this increased resistance.
Whole draft genome analysis of A. avenae 83 shows that the aac(2')-IIa gene is
carried by the novel IncP-1beta plasmid pAAA83, whereas the genetic carrier of
other strains, the IncP genomic island, is inserted into their chromosomes. The
difference in the nucleotides of the promoter region of aac(2')-IIa between
strain 83 and other strains indicates an additional transcription start site and
results in the increased transcription of aac(2')-IIa in strain 83. Moreover,
biological characterization of pAAA83 demonstrates that it can be transferred by
conjugation and maintained in the host cells. These results demonstrate that
acquisition of the aac(2')-IIa gene takes place in at least two ways and that the
gene module, which includes aac(2')-IIa and the downstream gene, may be an
important unit for the dissemination of antibiotic resistance.
PMID- 25131296
TI - Response.
PMID- 25131297
TI - Vmp1 regulates PtdIns3P signaling during autophagosome formation in Dictyostelium
discoideum.
AB - Generation and turnover of phosphatidylinositol 3-phosphate (PtdIns3P) signaling
is essential for autophagosome formation and other membrane traffic processes. In
both Dictyostelium discoideum and mammalian cells, autophagosomes are formed from
specialized regions of the endoplasmic reticulum (ER), called omegasomes, which
are enriched in the signaling lipid PtdIns3P. Vacuole membrane protein 1 (Vmp1)
is a multispanning membrane protein localized at the ER that is required for
autophagosome formation. There are conflicting reports in the literature as to
whether Vmp1 is strictly required or not for autophagy-related PtdIns3P signaling
and its hierarchical relationship with Atg1 and PI3K. We have now addressed these
questions in the Dictyostelium model. We show that Dictyostelium cells lacking
Vmp1 have elevated and aberrant PtdIns3P signaling on the ER, resulting in an
increased and persistent recruitment of Atg18 and other autophagic proteins. This
indicates that Vmp1 is not strictly essential for the generation of PtdIns3P
signaling but rather suggests a role in the correct turnover or modulation of
this signaling. Of interest, these PtdIns3P-enriched regions of the ER surround
ubiquitinated protein aggregates but are unable to form functional
autophagosomes. vmp1 null cells also have additional defects in macropinocytosis
and growth, which are not shared by other autophagy mutants. Remarkably, we show
that these defects and also the aberrant PtdIns3P distribution are largely
suppressed by the concomitant loss of Atg1, indicating that aberrant autophagic
signaling on the ER inhibits macropinocytosis. These results suggest that Atg1
functions upstream of Vmp1 in this signaling pathway and demonstrates a
previously unappreciated link between abnormal autophagy signaling and
macropinocytosis.
PMID- 25131298
TI - Lateral MoS2 p-n junction formed by chemical doping for use in high-performance
optoelectronics.
AB - This paper demonstrates a technique to form a lateral homogeneous 2D MoS2 p-n
junction by partially stacking 2D h-BN as a mask to p-dope MoS2. The fabricated
lateral MoS2 p-n junction with asymmetric electrodes of Pd and Cr/Au displayed a
highly efficient photoresponse (maximum external quantum efficiency of ~7000%,
specific detectivity of ~5 * 10(10) Jones, and light switching ratio of ~10(3))
and ideal rectifying behavior. The enhanced photoresponse and generation of open
circuit voltage (VOC) and short-circuit current (ISC) were understood to
originate from the formation of a p-n junction after chemical doping. Due to the
high photoresponse at low VD and VG attributed to its built-in potential, our
MoS2 p-n diode made progress toward the realization of low-power operating
photodevices. Thus, this study suggests an effective way to form a lateral p-n
junction by the h-BN hard masking technique and to improve the photoresponse of
MoS2 by the chemical doping process.
PMID- 25131299
TI - Variation in orgasm occurrence by sexual orientation in a sample of U.S. singles.
AB - INTRODUCTION: Despite recent advances in understanding orgasm variation, little
is known about ways in which sexual orientation is associated with men's and
women's orgasm occurrence. AIM: To assess orgasm occurrence during sexual
activity across sexual orientation categories. METHODS: Data were collected by
Internet questionnaire from 6,151 men and women (ages 21-65+ years) as part of a
nationally representative sample of single individuals in the United States.
Analyses were restricted to a subsample of 2,850 singles (1,497 men, 1,353 women)
who had experienced sexual activity in the past 12 months. MAIN OUTCOME MEASURES:
Participants reported their sex/gender, self-identified sexual orientation
(heterosexual, gay/lesbian, bisexual), and what percentage of the time they
experience orgasm when having sex with a familiar partner. RESULTS: Mean
occurrence rate for experiencing orgasm during sexual activity with a familiar
partner was 62.9% among single women and 85.1% among single men, which was
significantly different (F1,2848 = 370.6, P < 0.001, eta(2) = 0.12). For men,
mean occurrence rate of orgasm did not vary by sexual orientation: heterosexual
men 85.5%, gay men 84.7%, bisexual men 77.6% (F2,1494 = 2.67, P = 0.07, eta(2)
= 0.004). For women, however, mean occurrence rate of orgasm varied significantly
by sexual orientation: heterosexual women 61.6%, lesbian women 74.7%, bisexual
women 58.0% (F2,1350 = 10.95, P < 0.001, eta(2) = 0.02). Lesbian women had a
significantly higher probability of orgasm than did either heterosexual or
bisexual women (P < 0.05). CONCLUSIONS: Findings from this large dataset of U.S.
singles suggest that women, regardless of sexual orientation, have less
predictable, more varied orgasm experiences than do men and that for women, but
not men, the likelihood of orgasm varies with sexual orientation. These findings
demonstrate the need for further investigations into the comparative sexual
experiences and sexual health outcomes of sexual minorities.
PMID- 25131300
TI - The glutamate receptor GluN2 subunit regulates synaptic trafficking of AMPA
receptors in the neonatal mouse brain.
AB - The N-methyl-D-aspartate receptor (NMDAR) plays various physiological and
pathological roles in neural development, synaptic plasticity and neuronal cell
death. It is composed of two GluN1 and two GluN2 subunits and, in the neonatal
hippocampus, most synaptic NMDARs are GluN2B-containing receptors, which are
gradually replaced with GluN2A-containing receptors during development. Here, we
examined whether GluN2A could be substituted for GluN2B in neural development and
functions by analysing knock-in (KI) mice in which GluN2B is replaced with
GluN2A. The KI mutation was neonatally lethal, although GluN2A-containing
receptors were transported to the postsynaptic membrane even without GluN2B and
functional at synapses of acute hippocampal slices of postnatal day 0, indicating
that GluN2A-containing NMDARs could not be substituted for GluN2B-containing
NMDARs. Importantly, the synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazole
propionic acid receptor (AMPAR) subunit GluA1 was increased, and the
transmembrane AMPAR regulatory protein, which is involved in AMPAR synaptic
trafficking, was increased in KI mice. Although the regulation of AMPARs by
GluN2B has been reported in cultured neurons, we showed here that AMPAR-mediated
synaptic responses were increased in acute KI slices, suggesting differential
roles of GluN2A and GluN2B in AMPAR expression and trafficking in vivo. Taken
together, our results suggest that GluN2B is essential for the survival of
animals, and that the GluN2B-GluN2A switching plays a critical role in synaptic
integration of AMPARs through regulation of GluA1 in the whole animal.
PMID- 25131302
TI - An antibody tag-team: driving neutralization through escape.
AB - HIV rapidly mutates to escape antibody detection, and B cells counter this
mutation by continual evolution to restore recognition, serendipitously resulting
in the evolution of neutralizing activity in a fraction of infected individuals.
A recent Cell paper describes how antibody repertoires stochastically
collaborated, shaping the viral swarm and utilizing viral immune evasion to their
advantage.
PMID- 25131301
TI - The Dutch String-of-Pearls Stroke Study: protocol of a large prospective
multicenter genetic cohort study.
AB - BACKGROUND: In the last couple of years, genome-wide association studies have
largely altered the scope in genetic research in diseases in which both
environmental and genetic risk factors contribute to the disease. To date, the
genetic risk loci identified in stroke have lagged behind those in other complex
diseases, possibly because of the heterogeneity of stroke phenotypes.
Sufficiently large cohorts with well-defined and detailed phenotyping of stroke
patients are needed to identify additional genetic risk loci. DESIGN: The String
of-Pearls Institute is a unique partnership between all eight University Medical
Centers in the Netherlands. It was established in 2007 by the Netherlands
Federation of University Medical Centers, and it conducts a large prospective
cohort study in which comprehensive clinical data, detailed phenotyping of
stroke, imaging data, and biomaterials are collected in a large cohort of stroke
patients. AIMS: The study aims (1) to collect a sufficiently large prospective
cohort of stroke patients, with well-defined phenotypes; (2) to collect blood
samples and DNA in a standardized infrastructure, allowing for storing and
analyzing the samples in a uniform way; (3) to investigate associations between
genetic risk loci and stroke; (4) to create possibilities to perform
epidemiological studies in a well-defined hospital-based cohort of stroke
patients; and (5) to allow for pooling data with other large ongoing genetic
stroke studies.
PMID- 25131304
TI - MLL/KMT2A translocations in diffuse large B-cell lymphomas.
AB - Translocations of the histone-lysine N-methyltransferase 2A (KMT2A) gene,
formerly known as myeloid lymphoid leukemia/mixed-lineage leukemia gene, are
commonly associated with high-risk de novo or therapy-associated B-cell and T
cell lymphoblastic leukemias and myeloid neoplasms. Rare B-cell non-Hodgkin
lymphomas harboring KMT2A translocations have been reported, but information
regarding the clinical behavior of such cases is limited. Here, we describe two
extranodal diffuse large B-cell lymphomas (DLBCLs): a primary thyroid DLBCL and a
large cell transformation of a splenic marginal zone lymphoma, which displayed
complex karyotypes and translocations involving chromosome 11q23 targeting the
KMT2A gene. The pathological and clinical characteristics of these cases are
discussed in the context of previously reported lymphomas associated with
different types of KMT2A genetic aberrations. In contrast to the poor clinical
outcomes of patients with acute leukemias and myeloid neoplasms associated with
KMT2A translocations, patients with B-cell non-Hodgkin lymphomas, exhibiting
similar translocations, appear to respond well to immunochemotherapy. Our
findings add to the growing list of histone methyltransferase genes deregulated
in DLBCL and highlight the diversity of mechanisms, altering the function of
epigenetic modifier genes in lymphomas.
PMID- 25131303
TI - Grocery store podcast about omega-3 fatty acids influences shopping behaviors: a
pilot study.
AB - OBJECTIVES: To determine whether listening to a podcast about omega-3 fatty acids
(n-3s) while grocery shopping increased shoppers' awareness about and purchases
of seafood and other foods rich in n-3s. METHODS: Repeated-measures design with a
convenience sample (n = 56) of grocery shoppers who listened to the podcast while
shopping. Pre- and postintervention semistructured interviews were conducted. The
Theory of Reasoned Action was the study's framework. RESULTS: Shoppers were
primarily females (mean age, 41 +/- 15.3 years). Their perceived ability to buy
[t(55) = 6.27, P < .0001] and perceived importance regarding buying [t(55) =
3.38, P < .01] n-3-rich foods improved significantly. At least 1 n-3 rich food
(mean, 1.5 +/- 0.8) was purchased by 30%, and 79% planned future purchases.
CONCLUSION AND IMPLICATIONS: Podcasts may effectively communicate nutrition
information. More research with a larger sample size is needed to evaluate the
effects of the podcast on long-term changes in shopping behavior.
PMID- 25131305
TI - Role of turmeric in oxidative modulation in end-stage renal disease patients.
AB - Oxidative stress is considered as a major player in uremia-associated morbidity
and mortality in hemodialysis (HD) patients. The aim of this study was to
evaluate the effects of turmeric on oxidative stress markers in HD patients. This
study was a prospective and double-blind randomized clinical trial. Fifty HD
patients aged 18-60 years were recruited after fulfilling the inclusion criteria.
Patients were randomly categorized into 2 groups: trial group received turmeric
and control group received placebo for 8 weeks. Each patient in the trial group
received turmeric, whereas the control group received starch for the same 8
weeks. Plasma malondialdehyde (MDA), red blood cell (RBC) antioxidant enzyme
activities as glutathione peroxidase (GPX), glutathione reductase (GR), and
catalase (CAT), cholesterol, high-density lipoprotein-cholesterol, low-density
lipoprotein-cholesterol, triglyceride, albumin, and hemoglobin were also measured
before and after study. Although MDA level was reduced in both groups, the ratio
of decrease was significantly higher in the turmeric group (0.2 vs. 0.1, P =
0.040). Three enzymes of GPX, GR, and CAT levels were increased in both groups;
the ratio of increased was significantly higher in the turmeric group for the CAT
enzyme (0.73 vs. 0.54; P = 0.02). Also, significant elevation of albumin level in
the turmeric group compared with the control group was observed (P = 0.001).
Regular ingestion of turmeric reduces plasma MDA and increases RBC CAT activity
and plasma albumin levels in HD patients. Turmeric showed no adverse effects.
PMID- 25131306
TI - The expression and localization of Crb3 in developmental stages of the mice
embryos and in different organs of 1-week-old female mice.
AB - Crumbs homolog 3 (Crb3) is a member of the Crumbs family of proteins. This
protein may play a role in epithelial cell polarity and is associated with tight
junctions at the apical surface of epithelial cells. Alternative transcriptional
splice variants that encode different Crb3 isoforms have been characterized. The
expression of Crb3 mRNA and protein was observed in the pre-implantation mouse
embryos and different organs of 1-week-old mouse, and Crb3 expression was
primarily observed in the cytoplasm. Crb3 was expressed in a unique temporal
pattern in pre-implantation embryos. The main characteristic of Crb3 expression
was that the positive signals were stronger in the mature oocytes and zygotes
than in the 2-cell, 4-cell, and 8-cell stages and the morula, but a similar level
of high expression was observed in blastocysts. Therefore, the Crb3 expression
signal during the course of development process grew gradually stronger from the
2-cell stage to blastocyst. In addition, Crb3 protein was widely distributed in
each stage of the post-implantation embryos. Crb3 expression was observed in the
inner cell mass, trophoblast cells and endoderm of E4.5d embryos; in the chorion,
amnion, trophoblast cells, yolk sac endoderm and embryo ectoderm of E7.5d
embryos; in the amnion and limb bud of E8.0d embryos; and in the semicircular
canal epithelium, retina, lens vesicle and liver tissue of E13.5d embryos. Crb3
was expressed at different levels in different organs of 1-week-old mouse with
the strengths in the following order: kidney > small intestine > stomach > uterus
> liver > skeletal muscle > cerebellum > brain. The presence of Crb3 in many
organs and the regularity of Crb3 distribution in the process of mouse embryonic
development indicate that Crb3 protein plays an important role in establishing
and maintaining the polarity of mouse embryos.
PMID- 25131307
TI - Reversible nano-structuring of SrCrO3-delta through oxidation and reduction at
low temperature.
AB - Oxygen vacancies are often present in complex oxides as point defects, and their
effect on the electronic properties is typically uniform and isotropic.
Exploiting oxygen deficiency in order to generate controllably novel structures
and functional properties remains a challenging goal. Here we show that epitaxial
strontium chromite films can be transformed, reversibly and at low temperature,
from rhombohedral, semiconducting SrCrO(2.8) to cubic, metallic perovskite
SrCrO(3-delta). Oxygen vacancies in SrCrO(2.8) aggregate and give rise to ordered
arrays of {111}-oriented SrO(2) planes interleaved between layers of
tetrahedrally coordinated Cr(4+) and separated by ~1 nm. First-principle
calculations provide insight into the origin of the stability of such
nanostructures and, consistent with the experimental data, predict that the
barrier for O(2-) diffusion along these quasi-two-dimensional nanostructures is
significantly lower than that in cubic SrCrO(3-delta). This property is of
considerable relevance to solid oxide fuel cells in which fast O(2-) diffusion
reduces the required operating temperature.
PMID- 25131308
TI - Ursolic acid triggers nonprogrammed death (necrosis) in human glioblastoma
multiforme DBTRG-05MG cells through MPT pore opening and ATP decline.
AB - SCOPE: Ursolic acid, a natural pentacyclic triterpenic acid, possesses anticancer
potential and diverse biological effects, but its correlation with glioblastoma
multiforme cells and different modes of cell death is unclear. We studied the
cellular actions of human glioblastoma multiforme DBTRG-05MG cells after ursolic
acid treatment and explored cell-selective killing effect of necrotic death as a
cell fate. METHODS AND RESULTS: Ursolic acid effectively reversed temozolomide
resistance and reduced DBTRG-05MG cell viability. Surprisingly, ursolic acid
failed to stimulate the apoptosis- and autophagy-related signaling networks. The
necrotic death was characterized by annexin V/propidium iodide double-positive
detection and release of high-mobility group protein B1 and lactate
dehydrogenase. These ursolic acid elicited responses were accompanied by reactive
oxygen species generation and glutathione depletion. Rapid mitochondrial
dysfunction was paralleled by the preferential induction of necrosis, rather than
apoptotic death. Mitochondrial permeability transition (MPT) is a phenomenon to
provide the onset of mitochondrial depolarization during cellular necrosis. The
opening of MPT pores that were mechanistically regulated by cyclophilin D, and
adenosine triphosphate decline occurred in treated necrotic DBTRG-05MG cells.
Cyclosporine A (an MPT pore inhibitor) prevented ursolic acid-provoked necrotic
death and the acid-involved key regulators. CONCLUSION: Our study is the first to
report that ursolic acid-modified mitochondrial function triggers defective death
by necrosis in DBTRG-05MG cells rather than augmenting programmed death.
PMID- 25131309
TI - In Vivo Evaluation of Chemical Composition of Eight Types of Urinary Calculi
Using Spiral Computerized Tomography in a Chinese Population.
AB - BACKGROUND: This study was conducted to evaluate the chemical composition of
eight types of urinary calculi using spiral computerized tomography (CT) in vivo.
METHODS: From October 2011 to February 2013, upper urinary tract calculi were
obtained from 122 patients in the department of urinary surgery of the First
Affiliated Hospital of Soochow University. All patients were scanned with a 64
detector row helical CT scanner using 6.50 mm collimation before
ureterorenoscopy. Data from the preoperative spiral CT scans and postoperative
chemical composition of urinary calculi were collected. RESULTS: The chemical
composition analysis indicates that there were five types of pure calculi and
three types of mixed calculi, including 39 calcium oxalate calculi, 12 calcium
phosphate calculi, 10 calcium carbonate calculi, 8 magnesium ammonium phosphate
calculi, 6 carbonated apatite, 21 uric acid/ammonium urate calculi, 10 uric
acid/calcium oxalate calculi, and 16 calcium oxalate/calcium phosphate calculi.
There were significant differences in the mean CT values among the five types of
pure calculi (P < 0.001). Furthermore, we also observed significant differences
in the mean CT values among three types of mixed calculi (P < 0.001). Significant
differences in the mean CT values were also found among eight types of urinary
calculi (P < 0.001). However, no statistically significant difference was
observed between the mean CT values of magnesium ammonium phosphate calculi and
uric acid/calcium oxalate calculi (P = 0.262). CONCLUSION: Our findings suggest
that spiral CT could be a promising tool for determining the chemical composition
of upper urinary tract calculi.
PMID- 25131311
TI - History of the Harvard ChemDraw project.
PMID- 25131310
TI - The effect of immunoadsorption with the Immusorba TR-350 column on coagulation
compared to plasma exchange.
AB - BACKGROUND AND OBJECTIVES: Plasma exchange (PE) and immunoadsorption with the
Immusorba TR-350 column (IA) are used to remove autoantibodies from plasma in
acute neurological autoimmune disorders. The impact of IA on coagulation and on
low molecular weight heparin (LMWH) levels in comparison with PE was
investigated. PATIENTS AND METHODS: In five patients with neurological autoimmune
disorders, coagulation parameters (global tests, coagulation factors) were
measured before and after PE or IA (Part A). In five other patients under
anticoagulation with LMWH, anti-Xa activity and global tests were measured before
and after the treatments (Part B). RESULTS: After PE, coagulation factors were
significantly reduced by 50-70%. After IA, a distinct reduction was observed for
fibrinogen, but not for antithrombin and most of the other coagulation factors.
Anti-Xa activity was reduced after PE (from 0.57 +/- 0.10 to 0.13 +/- 0.05 IU/ml)
and almost unchanged after IA. CONCLUSION: It is advisable to discontinue or to
reduce LMWH doses and to monitor coagulation parameters and anti-Xa activity
after PE or IA to decide about further LMWH dosing.
PMID- 25131312
TI - Vitamin D and the athlete: emerging insights.
AB - Interest in Vitamin D has risen considerably recently with many athletes now
advised to take daily vitamin D supplements. The reason for this interest is
partly not only attributed to the resurgence of the Vitamin D-deficient disease
rickets but also due to the discovery of a Vitamin D receptor in many tissues
suggesting a more global role for Vitamin D than previously considered. Unlike
the other vitamins that are obtained through the diet, Vitamin D is unique since
endogenous synthesis following ultraviolet B (UVB) exposure is the predominant
route of entry into systemic circulation. Moreover, Vitamin D could be better
classed as a seco-steroid, given that its structure is similar to that of a
steroid, and its production is derived from a cholesterol precursor (7
dehydrocholesteol) in the skin. The classification of Vitamin D status is
currently subject to considerable debate with many authors opposing governing
body recommendations. Regardless of the suggested optimal concentration, there is
now growing evidence to suggest that many athletes are in fact Vitamin D
deficient, especially in the winter months largely as a consequence of inadequate
sun exposure, combined with poor dietary practices, although the consequences of
such deficiencies are still unclear in athletic populations. Impaired muscle
function and reduced regenerative capacity, impaired immune function, poor bone
health and even impaired cardiovascular function have all been associated with
low Vitamin D in athletes, however, to date, the majority of studies on Vitamin D
have described associations and much more research is now needed examining
causation.
PMID- 25131313
TI - Morphological characteristics of the cranial root of the accessory nerve.
AB - There has been the controversy surrounding the cranial root (CR) of the accessory
nerve. This study was performed to clarify the morphological characteristics of
the CR in the cranial cavity. Fifty sides of 25 adult cadaver heads were used.
The accessory nerve was easily distinguished from the vagus nerve by the dura
mater in the jugular foramen in 80% of 50 specimens. The trunk of the accessory
nerve from the spinal cord penetrated the dura mater at various distances before
entering the jugular foramen. In 20% of the specimens there was no dural
boundary. In these cases, the uppermost cranial rootlet of the accessory nerve
could be identified by removing the dura mater around the jugular foramen where
it joined to the trunk of the accessory nerve at the superior vagal ganglion. The
cranial rootlet was formed by union of two to four short filaments emerging from
the medulla oblongata (66%) and emerged single, without filament (34%), and
usually joined the trunk of the accessory nerve directly before the jugular
foramen. The mean number of rootlets of the CR was 4.9 (range 2-9) above the
cervicomedullary junction. The CR of the accessory nerve was composed of two to
nine rootlets, which were formed by the union of two to four short filaments and
joined the spinal root of the accessory nerve. The CR is morphologically distinct
from the vagus nerve, confirming its existence.
PMID- 25131314
TI - Observation is a valid way of assessing common variables in typical babbling and
identifies infants who need further support.
AB - AIM: It is important to identify speech and language difficulties in children as
early as possible. This study investigated the validity of observing babbling
structure and consonant articulation. METHODS: We focused on the language
capabilities of children, with and without cleft palates, at 12 months of age (n
= 29) and 18 months of age (n = 38), comparing observations made by speech and
language pathologists on babbling structure and consonant articulation to audio
recordings phonetically transcribed by experts blinded to the aim of the study.
Descriptive cross-tabs, sensitivity, specificity and predictive values were
analysed to investigate the validity of agreement between the methods. RESULTS:
We found high mean agreement between the two methods (94%) and within the
observation (100%) and transcription (88.5%) teams when it came to canonical
babbling, high-pressure/oral stop consonants and anterior placement of bilabial
and dental/alveolar consonants. The observations had high specificity and
negative predictive values (0.90-1) at both ages, with low to moderate
sensitivity (0-0.86). However, there was low agreement, between and within the
groups, on the number of consonant types and the unproven predictive variable
glottal place of articulation. CONCLUSION: Previously suggested predictive
measures of babbling were shown to be valid and observation is a reliable method
of identifying children who need further support.
PMID- 25131315
TI - Endogenous concentrations, pharmacokinetics, and selected pharmacodynamic effects
of a single dose of exogenous GABA in horses.
AB - The anti-anxiety and calming effects following activation of the GABA receptor
have been exploited in performance horses by administering products containing
GABA. The primary goal of the study reported here was to describe endogenous
concentrations of GABA in horses and the pharmacokinetics, selected
pharmacodynamic effects, and CSF concentrations following administration of a
GABA-containing product. The mean (+/-SD) endogenous GABA level was 36.4 +/- 12.5
ng/mL (n = 147). Sixteen of these horses received a single intravenous and oral
dose of GABA (1650 mg). Blood, urine, and cerebrospinal fluid (n = 2) samples
were collected at time 0 and at various times for up to 48 h and analyzed using
LC-MS. Plasma clearance and volume of distribution was 155.6 and 147.6 L/h and
0.154 and 7.39 L for the central and peripheral compartments, respectively.
Terminal elimination half-life was 22.1 (intravenous) and 25.1 (oral) min. Oral
bioavailability was 9.81%. Urine GABA concentrations peaked rapidly returning to
baseline levels by 3 h. Horses appeared behaviorally unaffected following oral
administration, while sedative-like changes following intravenous administration
were transient. Heart rate was increased for 1 h postintravenous administration,
and gastrointestinal sounds decreased for approximately 30 min following both
intravenous and oral administration. Based on a limited number of horses and time
points, exogenously administered GABA does not appear to enter the CSF to an
appreciable extent.
PMID- 25131316
TI - From yeast to patient neurons and back again: powerful new discovery platform.
AB - No disease-modifying therapies are available for synucleinopathies, including
Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple systems
atrophy (MSA). The lack of therapies has been impeded by a paucity of validated
drug targets and problematic cell-based model systems. New approaches are
therefore needed to identify genes and compounds that directly target the
underlying cellular pathologies elicited by the pathological protein, alpha
synuclein (alpha-syn). This small, lipid-binding protein impinges on
evolutionarily conserved processes such as vesicle trafficking and mitochondrial
function. For decades, the genetically tractable, single-cell eukaryote, budding
yeast, has been used to study nearly all aspects of cell biology. More recently,
yeast has revealed key insights into the underlying cellular pathologies caused
by alpha-syn. The robust cellular toxicity caused by alpha-syn expression
facilitates unbiased high-throughput small-molecule screening. Critically, one
must validate the discoveries made in yeast in disease-relevant neuronal models.
Here, we describe two recent reports that together establish yeast-to-human
discovery platforms for synucleinopathies. In this exemplar, genes and small
molecules identified in yeast were validated in patient-derived neurons that
present the same cellular phenotypes initially discovered in yeast. On
validation, we returned to yeast, where unparalleled genetic approaches
facilitated the elucidation of a small molecule's mode of action. This approach
enabled the identification and neuronal validation of a previously unknown
"druggable" node that interfaces with the underlying, precipitating pathologies
caused by alpha-syn. Such platforms can provide sorely needed leads and fresh
ideas for disease-modifying therapy for these devastating diseases.
PMID- 25131317
TI - [Hepatitis due to secondary syphilis].
PMID- 25131319
TI - Communication satisfaction of professional nurses working in public hospitals.
AB - AIM: This study aimed to establish and describe the level of communication
satisfaction that professional nurses experience in selected public hospitals in
the City of Johannesburg, South Africa. BACKGROUND: The success of any
organisation depends on the effectiveness of its communication systems and the
interaction between staff members. METHOD: Data were collected by means of
questionnaires, based on the Communication Satisfaction Questionnaire (CSQ), from
a sample of 265 professional nurses from different categories, chosen using a
disproportionate random stratified sampling method. RESULTS: The results
indicated poor personal feedback between nurse managers (operational managers)
and professional nurses, as well as dissatisfaction among nurse managers and
professional nurses with regard to informal communication channels. A lack of
information pertaining to policies, change, financial standing and achievements
of hospitals was identified. CONCLUSION: Nurse managers should play a leadership
role in bringing staff of different departments together by creating interactive
communication forums for the sharing of ideas. IMPLICATIONS FOR NURSING
MANAGEMENT: The results emphasise the need for nurse managers to improve
communication satisfaction at all levels of the hospital services in order to
enhance staff satisfaction and create a positive working environment for staff
members.
PMID- 25131318
TI - Bouveret's syndrome.
PMID- 25131320
TI - Increased prevalence of autoimmune diseases in functional gastrointestinal
disorders: case-control study of 23471 primary care patients.
AB - BACKGROUND: There is increasing evidence that impaired mucosal defence mechanisms
are implicated in the pathogenesis of the functional gastrointestinal disorders
(FGIDs), allowing inappropriate immune activation. AIM: To test the hypothesis
that an excess of autoimmune disorders among sufferers, using a large primary
care database to examine this. METHODS: Cases were diagnosed with FGIDs -
irritable bowel syndrome (IBS), functional dyspepsia (FD), chronic idiopathic
constipation (CIC), and multiple FGIDs. Controls were those without FGIDs.
Prevalence of autoimmune disorders was compared between cases and controls using
odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We included 23,471
patients (mean age 51.4 years, 66.1% female). Prevalence of autoimmune disorders
was greater among all FGIDs, compared with controls without. In those with FD (OR
1.35; 95% CI 1.12-1.63), CIC (OR 1.75; 95% CI 1.11-2.75), or multiple FGIDs (OR
1.49; 95% CI 1.25-1.77) this was statistically significant after controlling for
age and gender. Rheumatological autoimmune disorders were significantly more
frequent in those with FD (OR 1.44; 95% CI 1.15-1.80), CIC (OR 1.84; 95% CI 1.08
3.13), or multiple FGIDs (OR 1.53; 95% CI 1.24-1.88), after controlling for age
and gender. However, endocrine autoimmune disorders were no more frequent in
those with FGIDs, after controlling for age and gender. CONCLUSIONS: In a large
sample of primary care patients, there was a significantly higher prevalence of
autoimmune disorders among those with FD, CIC, or multiple FGIDs not explained by
differences in age or gender. We were unable to control for concomitant drug use,
which may partly explain this association.
PMID- 25131321
TI - Timing of and outcomes after selective termination of anomalous fetuses in
dichorionic twin pregnancies.
AB - OBJECTIVE: The objective of this article is to determine if selective termination
(ST) of an anomalous dichorionic twin at early gestational age (GA) is associated
with a decreased risk of fetal loss and prematurity. METHOD: All patients who had
ST for dichorionic twin pregnancies from 2004 through 2010 at Mount Sinai Medical
Center were included. Data were collected via chart review and patient interview.
Two case-control analyses were carried out: first, cases were nonviable
deliveries, and controls were live births; and second, cases were live births <37
weeks' GA, and controls were live births >=37 weeks' GA. Univariable and then
multivariable analyses identified characteristics associated with pregnancy loss
and prematurity. RESULTS: Among 80 participants, there were four (5%) fetal
losses and 15 (19%) premature births. GA at ST was the only characteristic
associated with pregnancy loss in multivariable exact logistic regression [OR =
1.43, 95% CI (1.03, 2.26), P = 0.03]. GA at ST was the only characteristic
associated with premature delivery in multivariable exact logistic regression [OR
= 1.18, 95% CI (1.02, 1.37), P = 0.03]. CONCLUSION: This study suggests that ST
performed earlier in pregnancy is associated with decreased fetal loss and
prematurity.
PMID- 25131322
TI - Laparoscopic gastrectomy after coronary artery bypass grafting using the right
gastroepiploic artery: a report of two cases.
AB - We successfully executed laparoscopic distal gastrectomy in two patients who had
previously undergone coronary artery bypass grafting using the right
gastroepiploic artery (RGEA). A laparoscopic distal gastrectomy preserving the
RGEA graft with Roux-en-Y reconstruction was performed on two men, one 69 years
of age and one 73 years of age. In both cases, the RGEA was used during coronary
artery bypass grafting for the posterior descending branch. The laparoscopic
approach helped avoid injury to the RGEA associated with laparotomy and retractor
placement. In addition, the locations of ports necessary for laparoscopy were
situated away from the RGEA graft and from adhesions resulting from bypass. Using
typical laparoscopic settings, we were able to easily identify the grafted RGEA.
Thus, laparoscopic distal gastrectomy is not only less invasive than open
gastrectomy procedures, but it is also associated with a lower risk of injury to
the RGEA graft.
PMID- 25131323
TI - Transcervical approach to percutaneous endoscopic gastrostomy tube insertion in a
patient with head and neck cancer.
AB - This is the case of a 48-year-old woman with recurrent head and neck cancer. Six
years before presenting at our institution, she was diagnosed with a moderately
differentiated squamous cell carcinoma involving the right maxilla and underwent
surgical resection followed by chemoradiation. More recently, she presented at
our institution with oral bleeding and pain. Examination revealed severe trismus,
and biopsy demonstrated recurrent squamous cell carcinoma. She underwent surgical
resection with a plan for simultaneous placement of a feeding gastrostomy tube.
Owing to the near non-existent mouth opening, traditional per-oral placement of a
percutaneous endoscopic gastrostomy (PEG) tube was impossible. Intraoperatively,
following tumor resection, endoscopy was performed via direct pharyngeal access
through a right cervical incision. The PEG tube was then placed uneventfully.
Numerous studies have shown the superiority of PEG tubes over either
radiologically or surgically placed gastrostomy tubes. This report describes an
approach to PEG placement in a patient in whom per-oral placement was not
feasible.
PMID- 25131324
TI - Laparoscopic reduced port surgery for schwannoma of the sigmoid colon: a case
report.
AB - A 74-year-old woman who developed schwannoma of the sigmoid colon was referred to
our hospital for colonography to determine the cause of her stool occult blood.
Colonoscopy revealed a submucosal tumor, which measured 3 cm in diameter, in the
sigmoid colon. Endoscopic ultrasonography revealed a low echoic, homogeneous and
demarcated submucosal tumor that continued into the fourth layer of the colonic
wall. Gastrointestinal stromal, myogenic or neurogenic tumor was suspected, and
thus, laparoscopic sigmoidectomy was carried out. We used two ports during the
operation, a SILS Port in the umbilical region and a 12-mm port in the right
lower abdominal wall, and performed sigmoidectomy with D2 lymph node dissection.
Histological findings revealed spindle-like tumor cells with multiform nuclei.
The tumor was diagnosed by immunostaining as benign schwannoma of the sigmoid
colon. The conventional surgical treatment for schwannoma of the digestive tract
is partial resection, but if preoperative diagnosis is unknown, radical resection
with lymphadenectomy is acceptable for submucosal tumors in the digestive tract.
In this case, laparoscopic reduced port surgery using only one or two ports may
be more feasible and beneficial with regard to cosmesis and reduced postoperative
pain than conventional laparoscopic colectomy.
PMID- 25131325
TI - Sterile abdominal abscess resulting from remnant laparoscopic clips after
sigmoidectomy: a case report and literature review.
AB - The occurrence of intra-abdominal sterile abscesses due to remnant clips after
laparoscopic sigmoidectomy is rare. Here, we report one such case in a 74-year
old woman. Two years after laparoscopic sigmoidectomy, abdominal CT indicated an
area of fluid accumulation approximately 5 cm in diameter and located in the
middle of the abdominal cavity that contained a cluster of clips. Fine-needle
aspiration of the fluid was performed through the wall of the sigmoid colon. The
luminal fluid was found not to contain cancer cells on histological examination.
After 1 year, abdominal surgery was performed. The abscess was located in the
mesorectum at the anastomosis site; it was incised and a significant quantity of
ivory-white viscous solution containing a cluster of clips was extracted. This
case emphasizes the importance of reducing the number of clips used in
laparoscopic surgery.
PMID- 25131326
TI - Laparoscopic resection of hepatoblastoma: report of a case.
AB - Despite the increasing number of recent reports on laparoscopic resection of
malignant liver tumors in adults, there have been few reports involving children.
In this paper we discuss the laparoscopic resection of a hepatoblastoma in a 1
year-old boy. The CT scan revealed an exophytic hepatic tumor on S5 measuring 6 *
5 * 4 cm after preoperative chemotherapy. The operation time was 225 min with an
estimated blood loss of about 38 mL; intraoperative transfusion was not required.
Radiofrequency-assisted precoagulation was performed. The patient had an
uncomplicated recovery and started postoperative chemotherapy on postoperative
day 12. Our literature search revealed only five reported cases of laparoscopic
resection of hepatoblastoma in which there was no postoperative complication or
recurrence. Laparoscopic resection of a hepatoblastoma in a selected subgroup of
patients can be safe and feasible.
PMID- 25131327
TI - Laparoscopy assisted middle-segment-preserving pancreatectomy for multiple
pancreatic neuroendocrine tumors: report of a case.
AB - For multiple low-grade malignant tumors located in the pancreatic head and tail,
middle-segment-preserving pancreatectomy (MSPP) is sometimes indicated. However,
MSPP has rarely been performed laparoscopically. Here we report the first case of
laparoscopic MSPP for multiple pancreatic neuroendocrine tumors diagnosed
preoperatively under an endoscopic ultrasound-guided fine-needle aspiration
biopsy. A 70-year-old man had multiple small tumors located in the pancreatic
head, body and tail. Endoscopic ultrasound-guided fine-needle aspiration biopsy
with immunohistochemical staining made a definitive diagnosis of a pancreatic
neuroendocrine tumor (G1). To preserve the 5-cm pancreas body, we successfully
performed laparoscopic MSPP: subtotal stomach-preserving pancreaticoduodenectomy
followed by distal pancreatosplenectomy. Pathological examination revealed
negative surgical margin after resection. Postoperative course was uneventful,
and at 14 months after the operation, the patient remains tumor-free. The patient
has discontinued insulin supplement therapy but does use an oral hypoglycemic
agent. Laparoscopy-assisted MSPP, with reconstruction through a 6-cm transverse
incision, can be safely performed for selected cases of borderline and malignant
lesions.
PMID- 25131328
TI - Hand-assisted laparoscopic splenectomy for sclerosing angiomatoid nodular
transformation of the spleen complicated by chronic disseminated intravascular
coagulation: a case report.
AB - A 36-year-old man who presented with a nosebleed and anemia was referred to our
hospital. Laboratory test results showed platelet depletion, decreased levels of
fibrinogen, and increased fibrinogen degeneration products. CT showed a 13-cm
splenic tumor. T2 -weighted MRI revealed a high-intensity mass. We preoperatively
diagnosed splenic hemangioma with chronic disseminated intravascular coagulation
and scheduled an operation to relieve the disseminated intravascular coagulation.
We also performed hand-assisted laparoscopic splenectomy to ensure easy handling
of the splenomegaly. The resected specimen microscopically consisted of
hemorrhages and hemangiomatous lesions, and multiple angiomatoid nodules were
scattered and separated by fibrocollagenous stroma with inflammatory cells. Three
types of vessels (capillaries, sinusoids and small veins) were contained in the
angiomatoid nodules, and the pathological diagnosis was sclerosing angiomatoid
nodular transformation. The results of this case suggest that we should consider
sclerosing angiomatoid nodular transformation in the differential diagnosis of
patients with splenic tumors, as sclerosing angiomatoid nodular transformation
with hemangiomatous features may cause coagulation disorders for which
splenectomy should be performed.
PMID- 25131329
TI - Laparoscopic repair of Bochdalek hernia with intrathoracic kidney in a 2-year-old
child.
AB - Intrathoracic kidney with Bochdalek hernia is a very rare congenital anomaly.
Some case reports have discussed repair by laparotomy or thoracotomy. We report a
case in a child performed using a laparoscopic approach. A 2-year-old boy arrived
at our hospital with gastric volvulus caused by a left-sided Bochdalek hernia. CT
also showed a left-sided intrathoracic kidney. After conservative therapy for the
volvulus, laparoscopic repair of the diaphragmatic hernia was performed. The key
problem during the operation was the presence of the intrathoracic kidney. If
direct closure of the hernia had been performed without the intrathoracic kidney
having been relocated to the abdomen, a complete closure would have been
impossible because of the renal vessels. After the intrathoracic kidney was
relocated to the abdomen, the diaphragmatic defect was closed. The boy has been
doing well without complications for 5 years, and CT reveals that the left-sided
kidney is almost normally positioned.
PMID- 25131330
TI - Hybrid technique for laparoscopic incisional ventral hernia repair combining
laparoscopic primary closure and mesh repair.
AB - INTRODUCTION: Incisional ventral hernia is one of the most common surgical
complications after laparotomy. Laparoscopic repair of incisional ventral hernia
has been conducted recently, and the advantages of this procedure have been
reported. However, in large orifice cases, the recurrence rate is increased. To
improve recurrence rates in large cases, a hybrid method combining laparoscopic
primary closure and mesh repair can be applied. MATERIALS AND SURGICAL TECHNIQUE:
Monofilament thread was inserted into the abdominal cavity for hernia closure and
pulled from the other side of the orifice. The same procedure was performed from
the upper side to the lower side without closure, and all thread was placed in
line. Both sides of the thread were then introduced to the midline of the
incision through a subcutaneous route. This procedure was conducted with an
introducer. All threads were tied, and then a mesh was placed. DISCUSSION: Hybrid
techniques already combine mini-laparotomy for hernia closure and subsequent
laparoscopic intraoperative onlay mesh for reinforcement, but such techniques
require laparotomy. In our technique, closure of the linea alba does not require
laparotomy. All procedures were performed laparoscopically. This procedure is
very easy and safe, and does not require the abdominal cavity to be opened. Thus,
hybrid methods are effective for treating cases of incisional hernia involving a
large orifice.
PMID- 25131331
TI - The role of IgG4 (+) plasma cells in the association of Hashimoto's thyroiditis
with papillary carcinoma.
AB - Hashimoto's thyroiditis (HT) is considered to be a risk factor for the formation
of papillary carcinoma. The association of IgG4-related sclerosing disease with
tumor is reported to be as sporadic cases in many organs. In this study, it was
intended to re-classify the HT diagnosed cases on the basis of the existence of
IgG4 (+) plasma cells; to investigate the clinicopathologic and histopathologic
features of the both groups; and in addition, to evaluate the papillary carcinoma
prevalence in IgG4 (+) and IgG4 (-) HT cases as well as the prognostic parameters
between these groups. Totally 59 cases between the years 2008-2013, 29 of which
contain Hashimoto thyroiditis diagnosis in total thyroidectomy materials, and 30
of which contain the diagnosis of HT+papillary carcinoma, were included in the
study. The materials were immunohistochemically applied IgG and IgG4; and the
cases were classified in two groups as IgG4-positive HT and IgG4-negative HT
containing cases, on the basis of IgG4/IgG rate. All histopathologic and
clinicopathologic parameters between these two groups, as well as their
association with papillary carcinoma were investigated. Thirty eight (64.4%) of
total 59 cases were NonIgG4 thyroiditis, and 21 (35.5%) were IgG4 thyroiditis.
Tumors were detected in 14 (36.8%) of the NonIgG4 thyroiditis cases, and in 16
(76.1%) of the IgG4 thyroiditis cases. The association of IgG4 thyroiditis with
tumor is statistically significant (p < 0.004). Multifocality was found to be at
a higher rate in IgG4 thyroiditis cases. Perithyroidal extension was detected in
six of the cases with tumor, and five of the six cases were IgG4 thyroiditis
cases. The association of IgG4 (+) HT cases with increased papillary carcinoma
prevalence is suggestive of that IgG4 (+) plasma cells can play a role in
carcinogenesis in papillary carcinomas developed in HTs, without a chronic
sclerosing ground. In addition, although the number of cases is limited, the high
association of IgG4 (+) plasma cells with adverse prognostic parameters such as
multifocality and extrathyroidal extension is attention-grabbing. To render these
possibilities evaluable, studies to be carried out with larger case series are
needed.
PMID- 25131332
TI - IFITM3-containing exosome as a novel mediator for anti-viral response in dengue
virus infection.
AB - Interferon-inducible transmembrane proteins 1, 2 and 3 (IFITM1, IFITM2 and
IFITM3) have recently been identified as potent antiviral effectors that function
to suppress the entry of a broad range of enveloped viruses and modulate cellular
tropism independent of viral receptor expression. However, the antiviral effect
and mechanisms of IFITMs in response to viral infections remain incompletely
understood and characterized. In this work, we focused our investigation on the
function of the extracellular IFITM3 protein. In cell models of DENV-2 infection,
we found that IFITM3 contributed to both the baseline and interferon-induced
inhibition of DENV entry. Most importantly, our study for the first time
demonstrated the presence of IFITM-containing exosome in the extracellular
environment, and identified an ability of cellular exosome to intercellularly
deliver IFITM3 and thus transmit its antiviral effect from infected to non
infected cells. Thus, our findings provide new insights in the basic mechanisms
underlying the actions of IFITM3, which might lead to future development of
exosome-mediated anti-viral strategies using IFITM3 as a therapeutic agent.
Conceivably, variations in the basal and inducible levels of IFITMs, as well as
in intracellular and extracellular levels of IFITMs, might predict the severity
of dengue virus infections among individuals or across species.
PMID- 25131333
TI - Dietary squid ink polysaccharides ameliorated the intestinal microflora
dysfunction in mice undergoing chemotherapy.
AB - Gastrointestinal mucositis and infection by chemotherapy treatment are associated
with alteration of intestinal microflora and bacterial translocation due to the
potential damage induced by anti-cancer drugs on the intestinal barrier and
microbiota homeostasis. This study aimed to investigate the protective effect of
dietary polysaccharides on chemotherapy induced intestinal microflora
dysfunction. In the current contribution, with a mouse model intraperitoneally
injected with 50 mg kg(-1) of cyclophosphamide (Cy) for 2 days, we revealed that
polysaccharides from the ink of Ommastrephes bartrami (OBP) altered the
intestinal microflora composition. OBP retarded the excessive growth of
intestinal bacteria induced by cyclophosphamide, based on 16S rRNA gene (16S
rDNA) quantification. The clone libraries of intestinal bacteria 16S rDNA were
used to decipher the difference in bacterial community structures in different
groups of mice. Followed by RFLP evaluation and OTU abundance analysis, they
imply that OBP changed the intestinal microflora composition, in which the
quantity of probiotic Bifidobacterium got up-regulated but Bacteroidetes
decreased in mice undergoing chemotherapy. Our results may have important
implications for OBP as a functional food component or nutrient against
chemotherapy induced intestinal injury and potential pathogenic intestinal
disorders involving inflammation and infection.
PMID- 25131334
TI - Chimeric RNAs generated by intergenic splicing in normal and cancer cells.
AB - A hallmark of many neoplasias is chromosomal rearrangement, an event that
commonly results in the fusion of two separate genes. The RNA and protein
resulting from these gene fusions often play critical roles in cancer
development, maintenance, and progression. Traditionally, these fusion products
are thought to be produced solely due to DNA level changes and are therefore
considered unique to cancer. Recent advances in microarray and deep-sequencing
have revealed many more fusion transcripts. Surprisingly, some are without
detectable rearrangement at the DNA level. Reports have demonstrated that at
least some of these chimeric RNAs are generated via intergenic splicing. In this
review, we highlight three examples of these noncanonical chimeric transcripts
that are formed by trans-splicing or cis-splicing of adjacent genes and summarize
the knowledge we have regarding these noncanonical fusions. We discuss the
implications of the chimeric RNAs in both cancer and normal physiology, as some
of these fusion transcripts are found in normal, noncancerous cells with
sequences identical to those generated by canonical chromosomal translocation
found in cancer cells. Finally, we present methods that are currently being used
to discover additional chimeric RNAs.
PMID- 25131335
TI - Higher biodiversity is required to sustain multiple ecosystem processes across
temperature regimes.
AB - Biodiversity loss is occurring rapidly worldwide, yet it is uncertain whether few
or many species are required to sustain ecosystem functioning in the face of
environmental change. The importance of biodiversity might be enhanced when
multiple ecosystem processes (termed multifunctionality) and environmental
contexts are considered, yet no studies have quantified this explicitly to date.
We measured five key processes and their combined multifunctionality at three
temperatures (5, 10 and 15 degrees C) in freshwater aquaria containing different
animal assemblages (1-4 benthic macroinvertebrate species). For single processes,
biodiversity effects were weak and were best predicted by additive-based models,
i.e. polyculture performances represented the sum of their monoculture parts.
There were, however, significant effects of biodiversity on multifunctionality at
the low and the high (but not the intermediate) temperature. Variation in the
contribution of species to processes across temperatures meant that greater
biodiversity was required to sustain multifunctionality across different
temperatures than was the case for single processes. This suggests that previous
studies might have underestimated the importance of biodiversity in sustaining
ecosystem functioning in a changing environment.
PMID- 25131336
TI - Successful treatment of non-invasive bladder tumour in a haemophilia A patient
with high-responding inhibitors: a case report.
PMID- 25131338
TI - Prescribing patterns and adherence to medication among South-Asian, Chinese and
white people with type 2 diabetes mellitus: a population-based cohort study.
AB - AIM: To determine the prescribing of and adherence to oral hypoglycaemic agents,
insulin, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers
and statin therapy among South-Asian, Chinese and white people with newly
diagnosed diabetes. METHODS: The present study was a population-based cohort
study using administrative and pharmacy databases to include all South-Asian,
Chinese and white people aged >= 35 years with diabetes living in British
Columbia, Canada (1997-2006). Adherence to each class of medication was measured
using proportion of days covered over 1 year with optimum adherence defined as >=
80%. RESULTS: The study population included 9529 South-Asian, 14 084 Chinese and
143 630 white people with diabetes. The proportion of people who were prescribed
angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statin
or oral hypoglycaemic agents was <= 50% for all groups. South-Asian and Chinese
people had significantly lower adherence for all medications than white people,
with the lowest adherence to angiotensin-converting enzyme inhibitor treatment
(South-Asian people: adjusted odds ratio 0.37, 95% CI 0.34-0.39; P<0.0001;
Chinese people: adjusted odds ratio 0.50, 95% CI 0.47-0.54; P<0.0001) and statin
therapy (South-Asian people: adjusted odds ratio 0.47, 95% CI 0.41 - 0.53, P <
0.0001; Chinese people: adjusted odds ratio 0.72, 95% CI 0.67 - 0.77; P<0.0001)
compared with white people. CONCLUSION: Adherence to evidence-based
pharmacotherapy was substantially worse among the South-Asian and Chinese
populations. Care providers need to be alerted to the high levels of non
adherence in these groups and the underlying causes need to be investigated.
PMID- 25131337
TI - Toothbrushing after an erosive attack: will waiting avoid tooth wear?
AB - The purpose of this study was to determine if storage for up to 4 h in human
saliva results in a decrease of erosive tooth wear (ETW) and in an increase of
surface microhardness (SMH) of enamel samples after an erosive attack with
subsequent abrasion. Furthermore, we determined the impact of individual salivary
parameters on ETW and SMH. Enamel samples were distributed into five groups:
group 1 had neither erosion nor saliva treatment; groups 2-5 were treated with
erosion, then group 2 was placed in a humid chamber and groups 3-5 were incubated
in saliva for 30 min, 2 h, and 4 h, respectively. After erosion and saliva
treatments, all groups were treated with abrasion. Surface microhardness and ETW
were measured before and after erosion, incubation in saliva, and abrasion.
Surface microhardness and ETW showed significant changes throughout the
experiment: SMH decreased and ETW increased in groups 2-5, regardless of the
length of incubation in saliva. The results of groups 3-5 (exposed to saliva)
were not significantly different from those of group 2 (not exposed to saliva).
Exposure of eroded enamel to saliva for up to 4 h was not able to increase SMH or
reduce ETW. However, additional experiments with artificial saliva without
proteins showed protection from erosive tooth wear. The recommendation to
postpone toothbrushing of enamel after an erosive attack should be reconsidered.
PMID- 25131340
TI - Auditory velocity discrimination in the horizontal plane at very high velocities.
AB - We determined velocity discrimination thresholds and Weber fractions for sounds
revolving around the listener at very high velocities. Sounds used were a
broadband white noise and two harmonic sounds with fundamental frequencies of 330
Hz and 1760 Hz. Experiment 1 used velocities ranging between 288 degrees /s and
720 degrees /s in an acoustically treated room and Experiment 2 used velocities
between 288 degrees /s and 576 degrees /s in a highly reverberant hall. A third
experiment addressed potential confounds in the first two experiments. The
results show that people can reliably discriminate velocity at very high
velocities and that both thresholds and Weber fractions decrease as velocity
increases. These results violate Weber's law but are consistent with the
empirical trend observed in the literature. While thresholds for the noise and
330 Hz harmonic stimulus were similar, those for the 1760 Hz harmonic stimulus
were substantially higher. There were no reliable differences in velocity
discrimination between the two acoustical environments, suggesting that auditory
motion perception at high velocities is robust against the effects of
reverberation.
PMID- 25131339
TI - Graphene nanoribbons as a drug delivery agent for lucanthone mediated therapy of
glioblastoma multiforme.
AB - We report use of PEG-DSPE coated oxidized graphene nanoribbons (O-GNR-PEG-DSPE)
as agent for delivery of anti-tumor drug Lucanthone (Luc) into Glioblastoma
Multiformae (GBM) cells targeting base excision repair enzyme APE-1 (Apurinic
endonuclease-1). Lucanthone, an endonuclease inhibitor of APE-1, was loaded onto
O-GNR-PEG-DSPEs using a simple non-covalent method. We found its uptake by GBM
cell line U251 exceeding 67% and 60% in APE-1-overexpressing U251, post 24h.
However, their uptake was ~38% and 29% by MCF-7 and rat glial progenitor cells
(CG-4), respectively. TEM analysis of U251 showed large aggregates of O-GNR-PEG
DSPE in vesicles. Luc-O-GNR-PEG-DSPE was significantly toxic to U251 but showed
little/no toxicity when exposed to MCF-7/CG-4 cells. This differential uptake
effect can be exploited to use O-GNR-PEG-DSPEs as a vehicle for Luc delivery to
GBM, while reducing nonspecific cytotoxicity to the surrounding healthy tissue.
Cell death in U251 was necrotic, probably due to oxidative degradation of APE-1.
PMID- 25131341
TI - Not too late to take vitamin D supplements.
PMID- 25131342
TI - A colorimetric immunoassay for respiratory syncytial virus detection based on
gold nanoparticles-graphene oxide hybrids with mercury-enhanced peroxidase-like
activity.
AB - A novel colorimetric immunoassay for highly sensitive detection of respiratory
syncytial virus (RSV), one of the leading causes of severe lower respiratory
tract infections in all age groups, has been proposed based on Hg(2+)-stimulated
peroxidase-like activity of gold nanoparticles-graphene oxide (AuNPs-GO) hybrids.
This metal ion-enhanced immunoassay shows high promise in the field of biomedical
sciences.
PMID- 25131344
TI - Controlling extreme events on complex networks.
AB - Extreme events, a type of collective behavior in complex networked dynamical
systems, often can have catastrophic consequences. To develop effective
strategies to control extreme events is of fundamental importance and practical
interest. Utilizing transportation dynamics on complex networks as a prototypical
setting, we find that making the network "mobile" can effectively suppress
extreme events. A striking, resonance-like phenomenon is uncovered, where an
optimal degree of mobility exists for which the probability of extreme events is
minimized. We derive an analytic theory to understand the mechanism of control at
a detailed and quantitative level, and validate the theory numerically.
Implications of our finding to current areas such as cybersecurity are discussed.
PMID- 25131345
TI - Influence of genetic background on bleeding phenotype in the tail-tip bleeding
model and recommendations for standardization: communication from the SSC of the
ISTH.
PMID- 25131343
TI - Treatment with melatonin after onset of experimental uveitis attenuates ocular
inflammation.
AB - BACKGROUND AND PURPOSE: Uveitis is a prevalent intraocular inflammatory disease
and one of the most damaging ocular conditions. Pretreatment with melatonin
prevented ocular inflammation induced by an intravitreal injection of bacterial
LPS in the Syrian hamster. Here, we have assessed the anti-inflammatory effects
of melatonin administered after the onset of ocular inflammation. EXPERIMENTAL
APPROACH: The eyes of male Syrian hamsters were intravitreally injected with
vehicle or LPS. Melatonin was injected i.p. every 24 h, starting 12 or 24 h after
the LPS injection. A clinical evaluation (with a score index based on clinical
symptoms), the number of infiltrating cells, protein concentration and PGE2 and
PGF2alpha levels in the aqueous humour, as well as retinal NOS activity, lipid
peroxidation and TNF-alpha levels were assessed. Retinal function was assessed by
scotopic electroretinography, and light microscopy and immunohistochemistry were
used to evaluate the state of the retinal structure. KEY RESULTS: Both treatment
regimens with melatonin decreased clinical symptoms, reduced the leakage of cells
and proteins, and decreased PG levels in aqueous humour from eyes injected with
LPS. In addition, melatonin treatment blocked the decrease in scotopic
electroretinogram a- and b-wave amplitude, protected the retinal structure and
reduced the increase in NOS activity, lipid peroxidation and TNF-alpha levels,
induced by LPS. CONCLUSIONS AND IMPLICATIONS: These results indicate that
treatment with melatonin, starting after the onset of uveitis, attenuated ocular
inflammation induced by LPS in the Syrian hamster and support the use of
melatonin as a therapeutic resource for uveitis treatment.
PMID- 25131346
TI - Iatrogenic right coronary artery stenosis resulting from surgical tricuspid valve
replacement: case report and review of the literature.
AB - Iatrogenic injury to the right coronary artery (RCA) is a rare complication of
tricuspid valve surgery. We herein describe the first-ever report of RCA injury
related to tricuspid valve replacement surgery. A 38-year-old man with recurrent
tricuspid endocarditis underwent redo tricuspid valve replacement by means of a
minimally invasive right thoracotomy with a 32-mm St. Jude bioprosthetic valve.
His post-operative course was complicated by pulseless ventricular tachycardia
requiring CPR and defibrillation. Cardiac catheterization revealed a "kinked"
stenotic distal RCA. The lesion was noted to be flow limiting by fractional flow
reserve and was treated with two everolimus-eluting stents. The RCA runs in the
atrioventricular groove and is susceptible to injury especially in the region of
the posterior leaflet of the tricuspid valve, where the relationship of the
tricuspid annulus to the RCA is most intimate. Repair of surgically induced
coronary stenosis can be accomplished with percutaneous intervention.
PMID- 25131347
TI - The construction and legitimation of workplace bullying in the public sector:
insight into power dynamics and organisational failures in health and social
care.
AB - Health-care and public sector institutions are high-risk settings for workplace
bullying. Despite growing acknowledgement of the scale and consequence of this
pervasive problem, there has been little critical examination of the
institutional power dynamics that enable bullying. In the aftermath of large
scale failures in care standards in public sector healthcare institutions, which
were characterised by managerial bullying, attention to the nexus between
bullying, power and institutional failures is warranted. In this study, employing
Foucault's framework of power, we illuminate bullying as a feature of structures
of power and knowledge in public sector institutions. Our analysis draws upon the
experiences of a large sample (n = 3345) of workers in Australian public sector
agencies - the type with which most nurses in the public setting will be
familiar. In foregrounding these power dynamics, we provide further insight into
how cultures that are antithetical to institutional missions can arise and seek
to broaden the debate on the dynamics of care failures within public sector
institutions. Understanding the practices of power in public sector institutions,
particularly in the context of ongoing reform, has important implications for
nursing.
PMID- 25131349
TI - What's in this issue?
PMID- 25131350
TI - Critical care nurses as dual agents: enhancing inter-professional collaboration
or hindering patient advocacy?
PMID- 25131348
TI - Fiber intake and plasminogen activator inhibitor-1 in type 2 diabetes: Look AHEAD
(Action for Health in Diabetes) trial findings at baseline and year 1.
AB - Plasminogen activator inhibitor 1 (PAI-1) is elevated in obese individuals with
type 2 diabetes and may contribute, independently of traditional factors, to
increased cardiovascular disease risk. Fiber intake may decrease PAI-1 levels. We
examined the associations of fiber intake and its changes with PAI-1 before and
during an intensive lifestyle intervention (ILI) for weight loss in 1,701 Look
AHEAD (Action for Health in Diabetes) participants with dietary, fitness, and PAI
1 data at baseline and 1 year. Look AHEAD was a randomized cardiovascular disease
trial in 5,145 overweight/obese patients with type 2 diabetes, comparing ILI
(goal of >=7% reduction in baseline weight) with a control arm of diabetes
support and education. ILI participants were encouraged to consume vegetables,
fruits, and grain products low in sugar and fat. At baseline, median fiber intake
was 17.9 g/day. Each 8.3 g/day higher fiber intake was associated with a 9.2%
lower PAI-1 level (P=0.008); this association persisted after weight and fitness
adjustments (P=0.03). Higher baseline intake of fruit (P=0.019) and high-fiber
grain and cereal (P=0.029) were related to lower PAI-1 levels. Although
successful in improving weight and physical fitness at 1 year, the ILI in Look
AHEAD resulted in small increases in fiber intake (4.1 g/day, compared with -2.35
g/day with diabetes support and education) that were not related to PAI-1 change
(P=0.34). Only 31.3% of ILI participants (39.8% of women, 19.1% of men) met daily
fiber intake recommendations. Increasing fiber intake in overweight/obese
individuals with diabetes interested in weight loss is challenging. Future
studies evaluating changes in fiber consumption during weight loss interventions
are warranted.
PMID- 25131356
TI - Effect of intravenous infusion of dobutamine hydrochloride on the development of
early postoperative cognitive dysfunction in elderly patients via inhibiting the
release of tumor necrosis factor-alpha.
AB - To investigate the effects of dobutamine hydrochloride on early postoperative
cognitive dysfunction (POCD) and plasma tumor necrosis factor (TNF)-alpha
concentration in patients undergoing hip arthroplasty, 124 patients undergoing
unilateral total hip arthroplasty, aged 70-92 years old, were randomly assigned
to four groups (n=31) as follows: a control group of patients receiving only
saline (intravenous infusion, i.v.); and groups receiving 2, 4, or 6MUgkg(-1)min(
1) (i.v.) of dobutamine hydrochloride. Cognitive functions were assessed on the
day before surgery (T1), and the 1st day (T2), 3rd day (T3), and 7th day (T4)
postsurgery using the Mini Mental State Examination (MMSE). The plasma TNF-alpha
protein level was determined 10min before anesthesia (Ta), and 10min (Tb), 30min
(Tc), and 60min (Td) after anesthesia by an enzyme-linked immunosorbent assay.
Cognitive disorder was observed within the first 3 days after hip arthroplastic
surgery, and it had recovered 7 days after the operation in the control group of
patients. Administration of 2 or 4MUgkg(-1)min(-1) dobutamine hydrochloride was
able to reverse the early POCD. Simultaneously, an increase of plasma TNF-alpha
levels 30min after anesthesia was observed (41.34+/-9.61 vs. 27.75+/-5.45), which
was significantly suppressed by the administration of low-dose dobutamine
hydrochloride (29.23+/-7.32 vs. 41.34+/-9.61) but not by high-dose dobutamine
hydrochloride (45.9+/-12.11 vs. 41.34+/-9.61). Together, our data indicated that
the plasma concentration of TNFalpha was engaged in the effect of dobutamine
hydrochloride on POCD.
PMID- 25131357
TI - A matter of trial and error for motor learning.
AB - Climbing fiber inputs to cerebellar Purkinje cells are thought to carry error
signals that can trigger motor learning across multiple time scales. A new study
by Kimpo et al. finds that the potency of climbing fibers as instructive signals
for adaptation of the vestibulo-ocular reflex depends on task conditions.
PMID- 25131358
TI - Basal ganglia: racing to say no.
AB - How we choose one action over another has intrigued neuroscientists for decades.
Early models of decision-making involved a race between processes representing
alternative choices. To explain behaviour in complex decisions, for example,
where one must cancel an impending action, a Stop unit must also join the race.
Recent neuronal recordings have demonstrated just such a race between Go and Stop
processes in the basal ganglia. This is a landmark advance because it
neurophysiologically justifies the need for a Stop process in such tasks, and
very likely in other behaviours requiring rapid cancellation of impending
actions.
PMID- 25131360
TI - Livedoid vasculopathy (LV) associated with sticky platelets syndrome type 3 (SPS
type 3) and enhanced activity of plasminogen activator inhibitor (PAI-1)
anomalies.
PMID- 25131361
TI - Primary cutaneous anaplastic large cell lymphomas with 6p25.3 rearrangement
exhibit particular histological features.
AB - AIMS: CD30-positive primary cutaneous lymphoproliferative disorders include
several entities with differing clinical presentation but overlapping
histological features, including lymphomatoid papulosis and primary cutaneous
anaplastic large cell lymphoma (C-ALCL). DUSP22-IRF4 locus translocation is
present in 20-57% of C-ALCLs, and has also been described in a series of 11
lymphomatoid papulosis patients, where it was associated with a particular
biphasic histological pattern, including pagetoid reticulosis-type epidermal
infiltration. We aimed to study whether the presence of this translocation may
define distinctive histological features in C-ALCL. METHODS AND RESULTS: We
collected three cases of C-ALCL with histological features similar to those
described in the new variant of lymphomatoid papulosis with 6p25.3 rearrangement.
We studied their histological features and immunophenotype, using a panel of
antibodies against CD30, TCR-betaF1, TCR-gamma, CD4, CD8, CD20, Ki-67 and ALK.
FISH analyses were performed using an IRF4-DUSP22 break-apart probe for the study
of the 6p25.3 rearrangement. FISH results were positive in the three cases, which
all showed distinctive histological and immunohistochemical features: a diffuse
dermal infiltrate of atypical medium-to-large cells, and marked epidermotrophism
with small, atypical intra-epidermal lymphocytes. CONCLUSIONS: Our findings
suggest that the presence of 6p25.3 rearrangement might be related to this
particular biphasic pattern.
PMID- 25131362
TI - [Extrapulmonary tuberculosis].
AB - Each year, there are more than eight million new cases of tuberculosis and 1.3
million deaths. There is a renewed interest in extrapulmonary forms of
tuberculosis as its relative frequency increases. Among extrapulmonary organs,
pleura and lymph nodes are the most common. Their diagnosis is often difficult
and is based on clinical, radiological, bacteriological and histological
findings. Extrapulmonary lesions are paucibacillary and samplings, in most cases,
difficult to obtain, so diagnosis is often simply presumptive. Nucleic acid
amplification tests, which are fast and specific, have greatly facilitated the
diagnosis of some forms of extrapulmonary tuberculosis. However, their
sensitivity is poor and a negative test does not eliminate the diagnosis.
Treatment is the same as for pulmonary forms, but its duration is nine to 12
months for central nervous system and for bone tuberculosis. Corticosteroids are
indicated in meningeal and pericardial localizations. Complementary surgery is
used for certain complicated forms.
PMID- 25131363
TI - [Diaphragmatic bronchogenic cyst: an exceptional location].
AB - A 64-year-old man complained of persistent dyspnea and bilateral basi-thoracic
pain with shoulder irradiation. Chest computed tomography revealed a
heterogeneous left diaphragmatic mass, while magnetic resonance imaging showed
hypo-T1 and hyper-T2 signal. Positron-emission tomography did not show any
hypermetabolism. Video-assisted thoracic surgery was decided. At inspection,
tumour appeared within the posterior costal part of the diaphragmatic muscle.
Tumour resection was extended to a 8-cm-long portion of the lumbar part of
diaphragm. Diaphragm was repaired with non-absorbable interrupted sutures.
Postoperative course was uneventful. Final pathology revealed an intra
diaphragmatic bronchogenic cyst, which is an exceptional condition. Primary
diaphragmatic tumours are very rare and preoperative diagnosis cannot be
affirmed. Embryologic hypotheses (migration along the oesophagus or envelopment
within diaphragmatic precursors of an abnormal supernumerary lung bud) including
recent molecular findings of deregulated pathways (fibroblast growth factor-10
and NOTCH) are discussed.
PMID- 25131364
TI - [Sarcoidose in patient with chronic hepatitis C treated with pegylated
interferon].
AB - Induced sarcoidosis during therapy with interferon for chronic viral hepatitis C
involves mainly by isolated cutaneous lesions or with lung lesions. Systemic
forms are very rare. We report an observation. A 50-year-old patient developed a
systemic sarcoidosis two months after the end of treatment for hepatitis C with
pegylated interferon and ribavirin with lung, joint and hepatic manifestations.
After starting corticosteroid therapy, the evolution was favourable. Induced
sarcoidosis by interferon therapy is rare, treatment necessitates stopping
interferon, and sometimes corticosteroid therapy.
PMID- 25131359
TI - Control of neural circuit formation by leucine-rich repeat proteins.
AB - The function of neural circuits depends on the precise connectivity between
populations of neurons. Increasing evidence indicates that disruptions in
excitatory or inhibitory synapse formation or function lead to
excitation/inhibition (E/I) imbalances and contribute to neurodevelopmental and
psychiatric disorders. Leucine-rich repeat (LRR)-containing surface proteins have
emerged as key organizers of excitatory and inhibitory synapses. Distinct LRR
proteins are expressed in different cell types and interact with key pre- and
postsynaptic proteins. These protein interaction networks allow LRR proteins to
coordinate pre- and postsynaptic elements during synapse formation and
differentiation, pathway-specific synapse development, and synaptic plasticity.
LRR proteins, therefore, play a critical role in organizing synaptic connections
into functional neural circuits, and their dysfunction may contribute to
neuropsychiatric disorders.
PMID- 25131365
TI - [Place and role of the pleura in non-small cell lung cancer dissemination].
AB - INTRODUCTION: The pleural involvement (PLI) in non-small cell lung cancer (NSCLC)
has a poor prognosis, even though it might be very heterogeneous. PATIENTS AND
METHODS: A multicentric retrospective descriptive study was performed over 2329
patients who were operated for NSCLC between 1979 and 2010. The patients with PLI
were classified in P(Parietal)PLI and V(visceral)PLI and then each subdivided :
VPLI to peripheric (VPLI-P) and fissural (VPLI-F) and PPLI to mediastinal (PPLI
M) and costal (PPLI-C). Characteristics and survival were compared between the
subgroups as well as with patients without PLI (WPLI, n=1439). RESULTS: The sex
ratio was 2.8 (males: n=1713). The PLI patients were significantly younger, with
a less sex-ratio, less R0 resections (96% versus 98.7%, P=0.000076), and less N0
(60% vs 70%, P<10(-6)) as their 5-year survival (45.7% vs 55.5%, P<10(-6)). The
PLI was related to the size of NSCLC (P<10(-6)) and N2 involvement (P=0.0020). It
was less frequent after neoadjuvant treatment (36.2% vs 39.1% P=0.03). In the
VPLI-F or PPLI-M, pneumonectomies were more frequent (P<10(-6)). In VPLI-P
(n=196/561), there were more pN1 and pN2 (P=0.0065) with a 5-year survival of
42.9% vs 54.4%, P=0.013. In multivariate analysis, the PLI was not an independent
prognostic factor contrary to age, sex, type of resection, pT and pN. CONCLUSION:
The pleura play a major role in NSCLC dissemination. Its involvement affects pN,
the type of surgical resection and justifies the use of neoadjuvant treatment.
PMID- 25131366
TI - [Lung cancer surgery in solid organ transplanted patients].
AB - BACKGROUND: The incidence of lung cancer is reputed to be higher and prognosis
worse in solid organ transplant recipients than in the general population. Our
purpose was to review the results of surgery in this group of patients. METHODS:
We retrospectively reviewed 49 male and 6 female patients; mean aged 60.6 years
(38-85). Transplanted organ was heart (n = 37), kidney (n=12), liver (n = 5) and
both-lungs (n = 1); 48 patients had smoking habits and 42 heavy comorbidities
(76.4%). Lung cancer was diagnosed during surveillance (78.2%, n = 43) or because
of symptoms (21.8%, n = 12). We reviewed TNM and other main characteristics,
among them histology (squamous-cell-carcinoma n = 23, adenocarcinomas n = 24,
others n = 8). RESULTS: Surgery consisted of: exploratory thoracotomy (n = 2),
wedge resections (n = 6), segmentectomy (n = 1), lobectomy (n = 42),
pneumonectomy (n = 4). Postoperative mortality was 7.4% (n = 4) and complication
rate 34.5% (n = 19). Five-year survival rate was 46.4% (65.4% for stage I
patients, n = 25). Among the 35 dead patients during follow-up, 14 died of their
lung cancer (40%). Two had been re-operated from another lung cancer: one after 3
and 8 years who survived 16 years, and the other after 2 years who survived 70
months. CONCLUSIONS: Surgery results are good and postoperative events acceptable
despite theoretically increased risks. This also supports performing a close
follow-up of transplanted patients and particularly those with smoking history in
view of detecting lung cancer appearing at an early stage.
PMID- 25131367
TI - [Epidemiology of tuberculosis].
AB - Tuberculosis is a contagious disease caused by Mycobacterium tuberculosis. It
represents, according to World Health Organization (WHO), one of the most leading
causes of death worldwide. With nearly 8 million new cases each year and more
than 1 million deaths per year, tuberculosis is still a public health problem.
Despite of the decrease in incidence, morbidity and mortality remain important
partially due to co-infection with human immunodeficiency virus and emergence of
resistant bacilli. All WHO regions are not uniformly affected by TB. Africa's
region has the highest rates of morbidity and mortality. The epidemiological
situation is also worrying in Eastern European countries where the proportion of
drug-resistant tuberculosis is increasing. These regional disparities emphasize
to develop screening, diagnosis and monitoring to the most vulnerable
populations. In this context, the Stop TB program, developed by the WHO and its
partner's, aims to reduce the burden of disease in accordance with the global
targets set for 2015.
PMID- 25131368
TI - [Pneumonectomy for benign disease: indication and factors affecting the
postoperative course].
AB - Pneumonectomy for benign disease is rare but may generate more postoperative
morbimortality than when performed for lung cancer. We questioned this assessment
and retrospectively reviewed 1436 pneumonectomies and 54 completions of which 82
and 10 performed for benign disease (5.7% and 18.5%, respectively): left n=65 and
right n=27. Indications were: post-tuberculosis destroyed lung (n=37),
aspergilloma (n=18), bronchiectasis (n=19), infection (n=5), congenital
malformations (n=5), inflammatory pseudotumor (n=3), trauma (n=2), post-radiation
(n=2) and mucormycosis (n=1). Pneumonectomy consisted of 48 standard and 44
pleuro-pneumonectomies. Stump coverage by flaps was performed in 66.3% (61/92).
Complications occurred in 21.7% (20/92) and postoperative deaths in 7.6% (7/92,
of which 5 with fungal infections), which was not different than what was
observed in lung cancer. There was no difference in fistula formation and
mortality regarding the side, the type of resection and the protective role of
stump coverage. Considering patients with fungal infections versus others,
mortality was 26.3% (n=5/19) and 2.7% (n=2/74), respectively (P=0.0028).
Pneumonectomy for benign disease achieves cure with acceptable mortality and
morbidity. However, presence of fungal infection should raise the attention for
possibility of increased postoperative risks.
PMID- 25131369
TI - [Tracheal tumor treated as asthma].
AB - Primary tumors of the trachea are very rare. In adults, the majority of them are
malignant. Schwannomas are exceedingly rare benign tumors in the tracheobronchial
tree. We report a case of a 37-year-old man who was hospitalized for increasing
dyspnea. He had been treated for bronchial asthma for the last 4 years with no
benefit. The CT scan of the chest and bronchoscopy identified a tracheal mass
that was prolapsed in the left stem bronchus. The patient did not remain free of
disease after endoscopic laser resection. So, surgical resection was made. The
tumor was excised at its base. A segment of the left stem bronchus was removed
and primary anastomosis was performed. The histopathologic diagnosis was of a
benign schwannoma without malignant elements. There was no recurrence during the
follow-up period. This case demonstrates that intratracheal masses should be
considered in patients with dyspnea or in patients with asthma refractory to
conventional therapy.
PMID- 25131370
TI - [Disseminated tuberculosis following infliximab therapy for Crohn disease: a case
report].
AB - Anti-tumor necrosis factor (TNF) therapy has been the major advance in the
treatment of inflammatory bowel disease, especially Crohn's disease. But there is
a higher risk of infections, especially tuberculosis (TB), in patients treated
with anti-TNFalpha. The authors report a case of disseminated tuberculosis with
the following features: pulmonary tuberculosis, left supra clavicular cervical
and meditational lymphadenopathy, bilateral pleural effusion, peritoneal and
splenic involvement. This disseminated tuberculosis was observed in a 39-year-old
woman who was treated by infliximab for refractory Crohn's disease. The evolution
with antituberculosis drugs was fatal, the death of the patient was due to
hepatic encephalitis. CONCLUSION: The physicians should always be aware in the
use of TNF-alpha blockers according to guidelines. Its recommended to realize a
complete pretherapeutic assessment and it is necessary to follow-up the patients
to detect possible reactivation of latent tuberculosis.
PMID- 25131371
TI - [Major pulmonary resections for lung cancer and thoracoscopic approach: some
reflections on published data].
AB - Video-assisted thoracic surgery has a renewed topicality in treating early stage
non-small cell lung cancer. Numerous publications show the benefits of this
surgical technique in comparison with conventional thoracotomy. However, some
surgeons are still apprehensive for its validity in lung cancer. Few works were
dedicated to the critical aspect of this new technique which generates silent
controversy and is far from having the general approval of all surgical teams. A
critical review of several papers disclosed some concerns related to this
approach, notably the risk of intra-operative technical problems and the
possibility of questionable results concerning cancer dissection and clearance. A
randomized clinical trial is now mandatory to confirm the safety and usefulness
of this technique.
PMID- 25131372
TI - [Primitive lung abscess: an unusual situation in children].
AB - INTRODUCTION: Lung abscess is a localized area of non tuberculosis suppurative
necrosis of the parenchyma lung, resulting in formation of a cavity containing
purulent material. This pathology is uncommon in childhood. CASE REPORT: A 3-year
6 month-old boy was admitted with prolonged fever and dyspnea. Chest X-ray showed
a non systemized, well limited, thick walled, hydric, and excavated opacity
containing an air-fluid level. Chest ultrasound examination showed a collection
of 6. 8 cm of diameter in the right pulmonary field with an air-fluid level.
Hemoculture showed Staphylococcus aureus. The patient received large spectrum
antibiotherapy. Three days after, he presented a septic shock and surgical
drainage was indicated. Histological examination confirmed the diagnosis of lung
abscess. Any underlying condition such as inoculation site, local cause or immune
deficiency, was noted and diagnosis of primary abscess was made. The patient
demonstrated complete recovery. He is asymptomatic with normal chest X-ray and
pulmonary function after 3 years of evolution. CONCLUSION: Lung abscess represent
a rare cause of prolonged fever in childhood. An underlying condition must be
excluded to eliminate secondary abscess.
PMID- 25131375
TI - Small RNA and degradome profiling reveals a role for miRNAs and their targets in
the developing fibers of Gossypium barbadense.
AB - microRNAs (miRNAs) are 20-24 nucleotide non-coding small RNAs that play important
roles in plant development. The stages of cotton fiber development include
initiation, elongation, secondary wall thickening (SWT) and maturation. We
constructed seven fiber RNA libraries representing the initiation, elongation and
SWT stages. In total, 47 conserved miRNA families and seven candidate miRNAs were
profiled using small RNA sequencing. Northern blotting and real-time polymerase
chain reaction (PCR) analyses revealed the dynamic expression of miRNAs during
fiber development. In addition, 140 targets of 30 conserved miRNAs and 38 targets
of five candidate miRNAs were identified through degradome sequencing. Analysis
of correlated expression between miRNAs and their targets demonstrated that
specific miRNAs suppressed the expression of transcription factors, SBP and MYB,
a leucine-rich receptor-like protein kinase, a pectate lyase, alpha-tubulin, a
UDP-glucuronic acid decarboxylase and cytochrome C oxidase subunit 1 to affect
fiber development. Histochemical analyses detected the biological activity of
miRNA156/157 in ovule and fiber development. Suppressing miRNA156/157 function
resulted in the reduction of mature fiber length, illustrating that miRNA156/157
plays an essential role in fiber elongation.
PMID- 25131373
TI - Early diagnosis of Gaucher disease in pediatric patients: proposal for a
diagnostic algorithm.
AB - Gaucher disease (GD) is caused by an enzyme deficiency that leads to the
accumulation of glycolipids in various organs. Although the signs and symptoms of
GD emerge in childhood in the majority of patients, the disease often remains
unrecognized for many years with delay of benefits of therapy or development of
irreversible complications. Based on published data and data from the
International Collaborative Gaucher Group Registry, an algorithm has been drafted
for early diagnosis of GD in pediatric patients. It will help hematologists in
promoting a timely diagnosis and early access to therapy for pediatric patients
with GD.
PMID- 25131376
TI - Sonography in carpal tunnel syndrome with normal nerve conduction studies.
AB - INTRODUCTION: We assessed the yield of high-resolution ultrasonography (HRUS) in
patients with clinically definite carpal tunnel syndrome (CTS) and normal nerve
conduction studies (NCS). METHODS: This blinded, prospective, cross-sectional
study involved 35 patients (60 hands) with clinically definite CTS and normal
NCS, and 20 controls (40 hands). Cross-sectional area (CSAs) of the median nerve
at the level of the pisiform bone and flexor retinaculum thickness (FRT) were
measured. RESULTS: CSA was abnormal in 48.6% of patients (confidence interval
32.0-65.2%, P = 0.95). FRT was increased in only 34.3% (18.3-49.7%), but was
independently abnormal in 2 patients. CSA abnormalities correlated with positive
provocative tests and sensory loss. The HRUS changes were mild. CONCLUSIONS: HRUS
confirms clinically diagnosed CTS in about half of the patients with normal NCS.
PMID- 25131377
TI - Alleviation of respiratory syncytial virus replication and inflammation by fungal
immunomodulatory protein FIP-fve from Flammulina velutipes.
AB - Respiratory syncytial virus (RSV) causes bronchiolitis in children followed by
inflammation and asthma-like symptoms. The development of preventive therapy for
this virus continues to pose a challenge. Fungal immunomodulatory proteins (FIPs)
exhibit anti-inflammatory function. FIP-fve is an immunomodulatory protein
isolated from Flammulina velutipes. To determine whether FIP-fve affects the
infection or consequence of immunity of RSV, we investigated viral titers of RSV
and inflammatory cytokine levels in vivo and in vitro. Oral FIP-fve decreased RSV
induced airway hyperresponsiveness (AHR), airway inflammation, and IL-6
expression in bronchoalveolar lavage fluid (BALF) of BALB/c mice. RSV replication
and interleukin 6 (IL-6) levels in RSV-infected HEp-2 cells were compared before
and after FIP-fve treatment. FIP-fve inhibited viral titers on plaque assay and
Western blot, as well as inhibited RSV-stimulated expression of IL-6 on ELISA and
RT-PCR. The results of this study suggested that FIP-fve decreases RSV
replication, RSV-induced inflammation and respiratory pathogenesis. FIP-fve is a
widely used, natural compound from F.velutipes that may be a safe agent for viral
prevention and even therapy.
PMID- 25131378
TI - Modulation of inflammation and pathology during dengue virus infection by p38
MAPK inhibitor SB203580.
AB - Dengue virus (DENV) infection could lead to dengue fever (DF), dengue hemorrhagic
fever (DHF) or dengue shock syndrome (DSS). The disease outcome is controlled by
both viral and host factors. Inflammation mediators from DENV-infected cells
could contribute to increased vascular permeability, leading to severe DHF/DSS.
Therefore, suppression of inflammation could be a potential therapeutic approach
for treatment of dengue patients. In this context, p38 MAPK (mitogen-activated
protein kinase) is a key enzyme that modulates the initiation of stress and
inflammatory responses. Here we show that SB203580, a p38 MAPK inhibitor,
suppressed the over production of DENV-induced pro-inflammatory mediators such as
TNF-alpha, IL-8, and RANTES from human PBMCs, monocytic THP-1, and granulocyte
KU812 cell lines. Oral administration of SB203580 in DENV-infected AG129 mice
prevented hematocrit rise and lymphopenia, limited the development of
inflammation and pathology (including intestine leakage), and significantly
improved survival. These results, for the first time, have provided experimental
evidence to imply that a short term inhibition of p38 MAPK may be beneficial to
reduce disease symptoms in dengue patients.
PMID- 25131379
TI - Anti-lipopolysaccharide factor isoform 3 from Penaeus monodon (ALFPm3) exhibits
antiviral activity by interacting with WSSV structural proteins.
AB - In innate immunity, antimicrobial peptides (AMPs) play a vital role in combating
microbial pathogens. Among the AMPs identified in Penaeus monodon, only anti
lipopolysaccharide factor isoform 3 (ALFPm3) has been reported to exhibit
activity against white spot syndrome virus (WSSV). However, the mechanism(s)
involved are still not clear. In the present study, ALFPm3-interacting proteins
were screened for from a WSSV library using the yeast two-hybrid screening
system, revealing the five potential ALFPm3-interacting proteins of WSSV186,
WSSV189, WSSV395, WSSV458 and WSSV471. Temporal transcriptional analysis in WSSV
infected P. monodon revealed that all five of these WSSV gene transcripts were
expressed in the late phase of infection (24h and 48h post-infection). Of these,
WSSV189 that was previously identified as a structural protein, was selected for
further analysis and was shown to be an enveloped protein by Western blot and
immunoelectron microscopy analyses. The in vitro pull-down assay using
recombinant WSSV189 (rWSSV189) protein as bait confirmed the interaction between
ALFPm3 and WSSV189 proteins. Moreover, pre-incubation of rWSSV189 protein with
rALFPm3 protein interfered with the latter's neutralization effect on WSSV in
vivo, as shown by the increased cumulative mortality of shrimp injected with WSSV
following prior treatment with pre-incubated rWSSV189 and rALFPm3 proteins
compared to that in shrimp pre-treated with rALFPm3 protein. Thus, ALFPm3 likely
performs its anti-WSSV action by binding to the envelope protein WSSV189 and
possibly other WSSV structural proteins.
PMID- 25131380
TI - Homing effect of adipose-derived stem cells to the injured liver: the shift of
stromal cell-derived factor 1 expressions.
AB - BACKGROUND: Whether systemically transplanted human adipose-derived stem cells
(ADSCs) homed to the injured liver in nude mice under stress with subsequent
hepatectomy (Hx) and ischemia-reperfusion (I/R) was investigated in the present
study. The types of cells in the liver that were involved in the homing of ADSCs
were clarified, with focus on the stromal-derived factor-1 (SDF-1)/C-X-C
chemokine receptor type 4 (CXCR-4) axis. METHODS: Adipose-derived stem cells were
transplanted intravenously immediately after 70% Hx and I/R. ADSCs were traced by
in vivo imaging for 24 h after transplantation and ADSCs were histologically
detected in the liver. SDF-1 and CXCR-4 expressions in the liver were evaluated
by real time RT-PCR. The immunohistochemical analysis of SDF-1 was also performed
to identify SDF-1 expressing cells in the liver. RESULTS: Adipose-derived stem
cells were found in various organs immediately following transplantation and
almost accumulated in remnant liver or spleen at 6 h after transplantation. ADSCs
were also histologically revealed in the harvested liver. Hx and I/R injury
significantly enhanced SDF-1 expressions regardless of ADSCs transplantation, and
only ADSC transplantation increased CXCR-4 expressions. The predominant SDF-1
positive cells in the liver were equally identified in parenchymal and non
parenchymal cells at 6 h, but shifted to non-parenchymal cells at 24 h after
transplantation. CONCLUSIONS: Systemically transplanted ADSCs homed to the
injured liver after transplantation, possibly based on the mechanisms of SDF
1/CXCR-4 axis. Therefore, systemic transplantation might be an effective and
practical route for the transplantation of ADSCs.
PMID- 25131381
TI - Sustaining dignity? food insecurity in homeless young people in urban Australia.
AB - ISSUE ADDRESSED: Food insecurity is recognised as an increasing problem in
disadvantaged and marginalised groups. The aim of this study was to investigate
issues associated with food insecurity and nutrition in young people
experiencing, or at risk of, homelessness in metropolitan Australia. METHODS:
Eight focus group discussions were conducted with 48 young people (aged between
15 and 25 years) in specialist homelessness services in central and south-western
Sydney. RESULTS: Participants described daily experiences of food insecurity,
persistent hunger and poverty. Structural barriers to food security and nutrition
were identified and included poverty and reduced physical access to fresh foods.
Participants also described a desire to save time, for convenience and to be
socially connected. Despite the hardships and the chaos of youth homelessness,
the groups were defined by their strength of character, resilience and hope for
the future. CONCLUSION: Homeless young people within central and south-western
Sydney report varying degrees of food insecurity, despite being supported by
specialist youth homelessness services. SO WHAT? A collaborative, multistrategic
approach with youth participation is required to further enhance the capacity of
youth services to improve food security, food access and the availability of
nutritious foods for homeless young people. A greater focus on advocacy and
policy action is also required to bring food security and nutrition to the
forefront of national efforts to improve the health and welfare of disadvantaged
groups.
PMID- 25131382
TI - Evolutionary ecology of microsporidia associated with the invasive ladybird
Harmonia axyridis.
AB - Invasive species are characterized by the rapid growth and spread of their
populations after establishing a foothold in new habitats, and there are now many
examples of such species negatively affecting biodiversity and the economy. It is
unclear why some species can become successful invaders, whereas most (even if
closely related) remain noninvasive. We previously proposed a hypothesis that
parasites associated with invading species can promote their invasive success if
they are harmless toward the invaders but harmful to their competitors and/or
predators in the newly colonized habitat. Here we discuss whether microsporidia
that have recently been discovered in the invasive ladybird Harmonia axyridis
contribute to its invasive success. We show that all H. axyridis beetles sourced
from diverse collection sites all over the world carry abundant microsporidia.
This suggests that both native and invasive H. axyridis populations are
associated with these tolerated parasites, which were likely to have existed in
native populations before expansion rather than being acquired in newly colonized
areas. We describe the pathogenesis of the microsporidia during different
developmental stages of H. axyridis and we address the possibility that the
predation of its infected eggs and larvae by competing native ladybird species
may lead to their infection and ultimately to their decline. Finally, we discuss
our initial hypothesis: microsporidia that are tolerated by an invasive vector
insect can be active against susceptible native competitors and/or predator
species.
PMID- 25131383
TI - Purification and characterization of alpha-acetolactate decarboxylase (ALDC) from
newly isolated Lactococcus lactis DX.
AB - BACKGROUND: Diacetyl (2,3-butanedione) is a common flavor aroma from fermented
dairy products. There is a need to screen new microorganisms that can efficiently
produce large amounts of diacetyl. RESULTS: A new lactic acid bacterium that
produced high concentrations of diacetyl was identified based on Gram staining,
microscopic examination and 16S rDNA sequence analysis as Lactococcus lactis DX.
Its alpha-acetolactate decarboxylase (ALDC) was purified using 0.45 g mL(-1)
ammonium sulfate precipitation, Sephacryl S-300 and S-200 HR and native-PAGE. The
purified ALDC displayed a monomer structure and had a molecular mass of about
73.1 kDa, which was estimated using SDS-PAGE. IR analysis showed that the ALDC
had a typical protein structure. The optimal temperature and pH for ALDC activity
were 40 degrees C and 6.5 respectively. The ALDC of L. lactis DX was activated
by Fe(2+) , Zn(2+) , Mg(2+) , Ba(2+) and Ca(2+) , while Cu(2+) significantly
inhibited ALDC activity. Leucine, valine and isoleucine activated the ALDC.
CONCLUSION: A strain that had high ability to produce diacetyl was identified as
L. lactis DX. The difference in diacetyl production may be due to the ALDC, which
is different from other ALDCs.
PMID- 25131384
TI - Discoveries of hydrogen sulfide as a novel cardiovascular therapeutic.
AB - Hydrogen sulfide (H2S) is an endogenously produced gaseous signaling molecule
that elicits a number of cytoprotective effects in mammalian species. H2S was
originally considered toxic at elevated levels, but 15 years ago the labile
molecule was discovered in mammalian tissue and termed a gasotransmitter, thus
opening the door for research aimed towards understanding its physiologic nature.
Since then, novel findings have depicted the beneficial aspects of H2S therapy,
such as vasodilation, antioxidant upregulation, inflammation inhibition, and
activation of anti-apoptotic pathways. These cytoprotective alterations
effectively treat multiple forms of cardiac injury at the preclinical level of
research. The field has progressed towards instituting novel H2S donors that
prove more effective at activating the subsequent cardioprotective enhancements
over longer time periods. As more findings explore the efficacy of H2S, research
focused on detection of sulfhydrated targets is on the rise. Understanding the
molecular mechanisms that stem from H2S treatment may lead the field towards
powerful therapeutics in the clinical setting. This review will discuss the
cytoprotective and cardioprotective effects of H2S therapy, provide analysis on
the molecular alterations that lead to these enhancements, and explore recently
developed therapeutics that may bring this gasotransmitter into the clinic in the
near future.
PMID- 25131385
TI - Biobased building blocks for the rational design of renewable block polymers.
AB - Block polymers (BPs) derived from biomass (biobased) are necessary components of
a sustainable future that relies minimally on petroleum-based plastics for
applications ranging from thermoplastic elastomers and pressure-sensitive
adhesives to blend compatibilizers. To facilitate their adoption, renewable BPs
must be affordable, durable, processable, versatile, and reasonably benign. Their
desirability further depends on the relative sustainability of the renewable
resources and the methods employed in the monomer and polymer syntheses. Various
strategies allow these BPs' characteristics to be tuned and enhanced for
commercial applications, and many of these techniques also can be applied to
manipulate the wide-ranging mechanical and thermal properties of biobased and
self-assembling block polymers. From feedstock to application, this review
article highlights promising renewable BPs, plus their material and assembly
properties, in support of de novo design strategies that could revolutionize
material sustainability.
PMID- 25131386
TI - Protective effect of ((4-tert-butylcyclohexylidene) methyl) (4-methoxystyryl)
sulfide, a novel unsymmetrical divinyl sulfide, on an oxidative stress model
induced by sodium nitroprusside in mouse brain: involvement of glutathione
peroxidase activity.
AB - OBJECTIVES: In this study, the antioxidant action of ((4-tert
butylcyclohexylidene) methyl) (4-methoxystyryl) sulfide, a novel unsymmetrical
divinyl sulfide, against oxidative damage induced by sodium nitroprusside (SNP)
in brains of mice was investigated. METHODS: Mice received SNP (0.335 MUmol/site,
intracerebroventricular) 30 min after administration of sulfide (10 mg/kg,
intragastrically). After 1 h, animals were sacrificed and the brains were removed
to biochemistry analysis. Thiobarbituric acid reactive species (TBARS), protein
carbonyl (PC) and non-protein thiol (NPSH) levels, as well as catalase (CAT),
superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase
(GR) and glutathione S-transferase (GST) activities were determined. KEY
FINDINGS: SNP increased TBARS and PC levels, CAT, GPx, GR and GST activities and
reduced NPSH levels. Administration of the sulfide attenuated the changes
produced by SNP and increased per se GPx activity in brains of mice.
Toxicological parameters revealed that this compound did not cause acute renal or
hepatic damage. CONCLUSIONS: In conclusion, ((4-tert-butylcyclohexylidene)
methyl) (4-methoxystyryl) sulfide protected against oxidative damage caused by
SNP in mouse brain. GPx activity is involved, at least in part, in the cerebral
antioxidant action of this compound.
PMID- 25131387
TI - Bone formation in peri-implant defects grafted with microparticles: a pilot
animal experimental study.
AB - AIM: This study aimed to evaluate the healing of peri-implant defects grafted
with microparticles (MPs). MATERIAL AND METHODS: Six domestic pigs received nine
standardized defects at the calvaria, and an implant was inserted in the middle
of each defect. The space between the implant and lateral bone portion was filled
with MP pellets (n = 18) or MP supernatant (n = 18) or left unfilled (n = 18).
After 14 and 28 days, three animals were sacrificed and specimens removed for
further processing. Samples were microradiographically and histologically
analysed. In addition, we immunohistochemically stained for anti-vWF as a marker
of angiogenesis. RESULTS: In the case of bone regeneration and vessel formation,
the null hypothesis can be partially rejected. After 14 and 28 days, no
significant difference was observed within groups regarding de novo bone
formation, bone density and osseointegration. However, superior vessel formation
was found at both time points. CONCLUSION: Microparticles represent a promising
treatment option to accelerate peri-implant vessel formation. Further studies are
needed to investigate the regenerative properties of MPs more precisely.
PMID- 25131388
TI - Correlation of plasma brain-derived neurotrophic factor and metabolic profiles in
drug-naive patients with bipolar II disorder after a twelve-week pharmacological
intervention.
AB - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is thought to be involved in
the pathophysiology of bipolar disorder (BD) and metabolic syndrome. We
investigated the correlation between plasma BDNF with mood symptoms and metabolic
indices in patients with BD-II over a 12-week pharmacological intervention.
METHOD: Drug-naive patients with BD-II (n=117) were recruited. Metabolic profiles
[cholesterol, triglyceride, HbA1C, fasting serum glucose, body mass index (BMI)]
and plasma BDNF wtrun "tblautotrun "tblsctrun "tbl_contere measured at baseline
and 2, 8, and 12 weeks after beginning medication. To adjust within-subject
dependence over repeated assessments, multiple linear regressions with
generalized estimating equation methods were used. RESULTS: Seventy-six (65.0%)
patients completed the intervention. Plasma BDNF levels were significantly
associated with BMI (P=9.6E-5), low-density lipoprotein (P=0.034) and total
(P=0.001) cholesterol, but not with the Hamilton Depression Rating Scale-17 and
Young Mania Rating Scale scores over the 12-week treatment. CONCLUSION: We found
initial evidence of a positive correlation between plasma BDNF levels and BMI,
low-density lipoprotein and total cholesterol in drug-naive patients with BD-II.
The specific function of BDNF in regulating and maintaining peripheral metabolic
health requires additional investigation.
PMID- 25131389
TI - Minimally Invasive Early Operative Treatment of Progressive Foot and Ankle
Deformity Associated With Charcot-Marie-Tooth Disease.
AB - Charcot-Marie-Tooth disease is a neuromuscular disorder that commonly results in
a predictable pattern of progressive bilateral lower extremity weakness,
numbness, contracture, and deformity, including drop foot, loss of ankle eversion
strength, dislocated hammertoes, and severe cavus foot deformity. Late stage
reconstructive surgery will be often necessary if the deformity becomes
unbraceable or when neuropathic ulcers have developed. Reconstructive surgery for
Charcot-Marie-Tooth deformity is generally extensive and sometimes staged.
Traditional reconstructive surgery involves a combination of procedures,
including tendon lengthening or transfer, osteotomy, and arthrodesis. The
described technique highlights our early surgical approach, which involves
limited intervention before the deformity becomes rigid, severe, or disabling. We
present 2 cases to contrast our early minimally invasive technique with
traditional late stage reconstruction. Charcot-Marie-Tooth disease affects
different muscles at various stages of disease progression. As 1 muscle becomes
weak, the antagonist will overpower it and cause progressive deformity. The focus
of the early minimally invasive approach is to decrease the forces that cause
progressive deformity yet maintain function, where possible. Our goal has been to
maintain a functional and braceable foot and ankle, with the hope of avoiding or
limiting the extent of future major reconstructive surgery. The presented cases
highlight the patient selection criteria, the ideal timing of early surgical
intervention, the procedure selection criteria, and operative pearls. The early
minimally invasive approach includes plantar fasciotomy, Achilles tendon
lengthening, transfer of the peroneus longus to the fifth metatarsal, Hibbs and
Jones tendon transfer, and hammertoe repair of digits 1 to 5.
PMID- 25131390
TI - Long-term functional outcomes and quality of life after oncologic surgery and
microvascular reconstruction in patients with oral or oropharyngeal cancer.
AB - CONCLUSIONS: Surgery for oral or oropharyngeal cancer with free-flap
reconstruction is associated with moderate but persistent functional and quality
of life (QoL) problems. Patient age, tumor stage, tumor site, and radiotherapy
were the main predictors of functional outcome. OBJECTIVES: To evaluate long-term
functional outcomes and QoL, and to determine their predictive factors in
patients with oral or oropharyngeal cancer after oncologic surgery and free-flap
reconstruction. METHODS: Patients who underwent surgery with free-flap
reconstruction for oral or oropharyngeal cancer between 2000 and 2009 who were
alive at least 1 year after therapy were included in this study. Patients
completed the Voice Handicap Index (VHI-10) questionnaire and the European
Organization for Research and Treatment of Cancer (EORTC) QoL questionnaires QLQ
C30 and H&N35. Swallowing was evaluated using the Dysphagia Outcome and Severity
Scale (DOSS) and by flexible fiberoptic laryngoscopy. RESULTS: Sixty-four
patients were included in the study. VHI-10 mean score was 11.2 +/- 9 and its
predictive factors were T stage (p = 0.005) and tumor involvement of the tongue
base (p = 0.01). The mean DOSS score was 4 +/- 0.8. Age (p = 0.008), gender (p =
0.04), and radiotherapy (p = 0.001) were the main predictive factors of the DOSS
score.
PMID- 25131391
TI - Gastroesophageal reflux and carcinoma of larynx or pharynx: a meta-analysis.
AB - CONCLUSION: The meta-analysis supported the proposition that the prevalence of
gastroesophageal reflux disease (GERD) was associated with laryngeal cancer,
particularly in the hospital-based control group and diagnosed by
esophagogastroduodenoscopy (EGD) or esophageal pH monitoring. However, no
significant association was found between GERD and pharyngeal carcinoma.
OBJECTIVES: A number of studies have been conducted to investigate the
relationship between gastroesophageal reflux and laryngeal or pharyngeal
carcinoma. The conclusions are still debated. METHODS: We conducted a systematic
review of studies associated with the prevalence of GERD in laryngeal or
pharyngeal cancer, published up to November 2013.Odds ratios (ORs) and
corresponding 95% confidence intervals (CIs) were estimated using random effects
models or fixed effects models, according to heterogeneity I(2). RESULTS: Ten
studies were included in this meta-analysis. On average, GERD was significantly
higher in the tumor tissue of the study group compared with normal tissue of the
control group (OR = 2.17, 95% CI = 1.50, 3.14; random effects analysis). The
pooled ORs for laryngeal carcinoma were 2.21 (95% CI = 1.53-3.19; I(2) = 97,
random effects model) and 3.76 (95% CI = 0.21-67.48; I(2) = 94, random effects
model) for pharyngeal carcinoma.
PMID- 25131392
TI - Factors associated with malnutrition in patients with head and neck cancer.
AB - CONCLUSIONS: Comorbidities as well as T classification were the primary
determinants for the nutritional status of patients with head and neck cancer.
OBJECTIVES: We aimed to elucidate the underlying conditions of malnutrition in
patients with head and neck cancer. METHODS: We retrospectively reviewed 726
patients diagnosed with head and neck cancer between 2004 and 2013. Associations
between malnutrition and clinical parameters were assessed using univariate and
multivariate analyses. RESULTS: Median body mass index was 21.5 (range 11.6
38.0). According to World Health Organization criteria, the nutritional status of
these patients was classified into four groups: underweight (18%), normal (63%),
overweight (17%), and obese (1%). Comorbidities were detected in 40% of patients.
Multivariate analysis revealed the following factors to be independent factors
associated with malnutrition: advanced T stage, metachronous cancer, collagen
disease, gastrointestinal disease, and pulmonary disease.
PMID- 25131393
TI - Long-term administration of vasopressin can cause Meniere's disease in mice.
AB - CONCLUSION: A new murine model of Meniere's disease has been developed, based on
long-term administration of vasopressin. Induction of vestibular dysfunction in
the present animal model can cause additional stress, by reducing inner ear blood
flow. Latanoprost, a selective agonist for the FP prostanoid receptor, may become
a new remedy for Meniere's disease. OBJECTIVE: The purpose of this study was to
develop a more suitable animal model, with a closer resemblance to the
pathophysiological process in Meniere's disease. METHODS: Adult CBA/J or ICR mice
were treated by subcutaneous injection of vasopressin for 5 days up to 8 weeks.
Morphological analyses were performed of the cochlea, vestibular end organs and
endolymphatic sac. The effect of latanoprost on the development of endolymphatic
hydrops was also examined. RESULTS: All experimental animals showed mild to
moderate endolymphatic hydrops, increasing in severity as the vasopressin
treatment was prolonged. Animals treated with vasopressin for 8 weeks showed
severe endolymphatic hydrops with partial loss of outer hair cells and spiral
ganglion cells. These animals also had a reversible vestibular dysfunction
following intratympanic injection of epinephrine. Latanoprost inhibited the
development of endolymphatic hydrops caused by vasopressin.
PMID- 25131396
TI - Assessing carbon and hydrogen isotopic fractionation of diesel fuel n-alkanes
during progressive evaporation.
AB - Compound-specific isotope analysis offers potential for fingerprinting of diesel
fuels, however, possible confounding effects of isotopic fractionation due to
evaporation need to be assessed. This study measured the fractionation of the
stable carbon and hydrogen isotopes in n-alkane compounds in neat diesel fuel
during evaporation. Isotope ratios were measured using a continuous flow gas
chromatograph/isotope ratio mass spectrometer. Diesel samples were progressively
evaporated at 24 +/- 2 degrees C for 21 days. Increasing depletion of deuterium
in nC12-nC17 alkanes in the remaining liquid with increasing carbon chain length
was observed. Negligible carbon isotope fractionation was observed. Preferential
vaporization was measured for the shorter chain n-alkanes and the trend decreased
with increasing chain length. The decrease in delta(2) H values indicates the
preferential vaporization of the isotopically heavier species consistent with
available quantitative data for hydrocarbons. These results are most important in
the application of stable isotope technology to forensic analysis of diesel.
PMID- 25131395
TI - Vasorelaxant effects of 1-nitro-2-phenylethene in rat isolated aortic rings.
AB - Previously, we showed that nitro-2-phenylethane is a vasorelaxant constituent of
the essential oil of Aniba canelilla. Here, we investigated the mechanisms
underlying the vascular effects of 1-nitro-2-phenylethene (NPe), a structural
analog of 1-nitro-2-phenylethane obtained synthetically, in rat isolated thoracic
aortic preparations. At 0.1-100 MUg/mL, NPe similarly relaxed endothelium-intact
or endothelium-denuded aortic preparations pre-contracted with 60mM KCl or with
phenylephrine (PHE, 1 MUM). Vasorelaxant effects of NPe against PHE-induced
contractions remained unaffected following blockade of potassium channels by TEA,
and inhibition of either nitric oxide synthase by l-NAME, cyclooxygenase by
indomethacin or guanylate cyclase by ODQ. In preparations maintained under Ca(2+)
free conditions, NPe significantly reduced the contractions induced (i) by PHE,
but not those evoked by caffeine, (ii) by CaCl2 in either PHE (in the presence of
1 MUM verapamil)- or KCl-stimulated preparations, (iii) by extracellular Ca(2+)
restoration in thapsigargin-treated aortic preparations, and (iv) by the
activator of protein kinase C phorbol-12,13-dibutyrate or the inhibitor of
protein tyrosine phosphatase sodium orthovanadate. It is concluded that NPe
induced an endothelium-independent vasorelaxation with potency greater than its
structural analog 1-nitro-2-phenylethane. Such action appears to occur
intracellularly probably through inhibition of contractile events that are
clearly independent of Ca(2+) influx from the extracellular milieu.
PMID- 25131394
TI - Heterozygous FGF8 mutations in patients presenting cryptorchidism and multiple
VATER/VACTERL features without limb anomalies.
AB - BACKGROUND: The acronym VATER/VACTERL association describes the combination of at
least three of the following cardinal features: vertebral defects, anorectal
malformations, cardiac defects, tracheoesophageal fistula with or without
esophageal atresia, renal malformations, and limb defects. Although fibroblast
growth factor-8 (FGF8) mutations have mainly found in patients with Kallmann
syndrome, mice with a hypomorphic Fgf8 allele or complete gene invalidation
display, aside from gonadotropin-releasing hormone deficiency, parts or even the
entire spectrum of human VATER/VACTERL association. METHODS: We performed FGF8
gene analysis in 49 patients with VATER/VACTERL association and 27 patients
presenting with a VATER/VACTERL-like phenotype (two cardinal features). RESULTS:
We identified two heterozygous FGF8 mutations in patients displaying either
VATER/VACTERL association (p.Gly29_Arg34dup) or a VATER/VACTERL-like phenotype
(p.Pro26Leu) without limb anomalies. Whereas the duplication mutation has not
been reported before, p.Pro26Leu was once observed in a Kallmann syndrome
patient. Both our patients had additional bilateral cryptorchidism, a key
phenotypic feature in males with FGF8 associated Kallmann syndrome. Each mutation
was paternally inherited. Besides delayed puberty in both and additional
unilateral cryptorchidism in one of the fathers, they were otherwise healthy.
Serum hormone levels downstream the gonadotropin-releasing hormone in both
patients and their fathers were within normal range. CONCLUSION: Our results
suggest FGF8 mutations to contribute to the formation of the VATER/VACTERL
association. Further studies are needed to support this observation.
PMID- 25131398
TI - Teen parties: who has parties, what predicts whether there is alcohol and who
supplies the alcohol?
AB - This study explores which youth are more likely to have parties at home, what
factors are associated with the presence of alcohol at parties, and who supplies
the alcohol. We collected data in 2011 and 2012 through telephone interviews with
1,121 teens living in 50 mid-sized California cities. Overall, about a quarter of
teens reported having had a party at their house in the past 12 months, of whom
39 % reported that there was alcohol at their last party. Multiple sources
supplied alcohol for most parties. Seventy-two percent of those having a party
stated that at least one of their parents knew about their last party, and 64 %
reported that a parent was home at least part of the time. Seventy percent of
youth who hosted a party with alcohol said that their parent(s) definitely knew
that there was alcohol at the party, 24 % replied that their parent(s) probably
knew, and only 5 % said that their parent(s) did not know that there was alcohol
at the party. Logistic regression analyses indicated that youth with parents who
host parties at home are themselves more likely to host parties at home. Having
alcohol at a party was positively related to the age of the teen and the number
of guests attending, and was negatively related to parents' awareness of the
party. However, we found no relationship between whether a parent was at home at
the time of the party and whether it included alcohol. These findings suggest
that teens who have parties with alcohol at home have parents who know that there
is alcohol at the party, even though only a small number of parents provided
alcohol for the party.
PMID- 25131397
TI - Understanding the determinants of substrate specificity in IMP family metallo
beta-lactamases: the importance of residue 262.
AB - In Gram-negative bacteria, resistance to beta-lactam antibacterials is largely
due to beta-lactamases and is a growing public health threat. One of the most
concerning beta-lactamases to evolve in bacteria are the Class B enzymes, the
metallo-beta-lactamases (MBLs). To date, penams and cephems resistant to
hydrolysis by MBLs have not yet been found. As a result of this broad substrate
specificity, a better understanding of the role of catalytically important amino
acids in MBLs is necessary to design novel beta-lactams and inhibitors. Two MBLs,
the wild type IMP-1 with serine at position 262, and an engineered variant with
valine at the same position (IMP-1-S262V), were previously found to exhibit very
different substrate spectra. These findings compelled us to investigate the
impact of a threonine at position 262 (IMP-1-S262T) on the substrate spectrum.
Here, we explore MBL sequence-structure-activity relationships by predicting and
experimentally validating the effect of the S262T substitution in IMP-1. Using
site-directed mutagenesis, threonine was introduced at position 262, and the IMP
1-S262T enzyme, as well as the other two enzymes IMP-1 and IMP-1-S262V, were
purified and kinetic constants were determined against a range of beta-lactam
antibacterials. Catalytic efficiencies (kcat /KM ) obtained with IMP-1-S262T and
minimum inhibitory concentrations (MICs) observed with bacterial cells expressing
the protein were intermediate or comparable to the corresponding values with IMP
1 and IMP-1-S262V, validating the role of this residue in catalysis. Our results
reveal the important role of IMP residue 262 in beta-lactam turnover and support
this approach to predict activities of certain novel MBL variants.
PMID- 25131399
TI - Morphogenesis of Streptomyces in submerged cultures.
AB - Members of the genus Streptomyces are mycelial bacteria that undergo a complex
multicellular life cycle and propagate via sporulation. Streptomycetes are
important industrial microorganisms, as they produce a plethora of medically
relevant natural products, including the majority of clinically important
antibiotics, as well as a wide range of enzymes with industrial application.
While development of Streptomyces in surface-grown cultures is well studied,
relatively little is known of the parameters that determine morphogenesis in
submerged cultures. Here, growth is characterized by the formation of mycelial
networks and pellets. From the perspective of industrial fermentations, such
mycelial growth is unattractive, as it is associated with slow growth,
heterogeneous cultures, and high viscosity. Here, we review the current insights
into the genetic and environmental factors that determine mycelial growth and
morphology in liquid-grown cultures. The genetic factors include cell-matrix
proteins and extracellular polymers, morphoproteins with specific roles in liquid
culture morphogenesis, with the SsgA-like proteins as well-studied examples, and
programmed cell death. Environmental factors refer in particular to those
dictated by process engineering, such as growth media and reactor set-up. These
insights are then integrated to provide perspectives as to how this knowledge can
be applied to improve streptomycetes for industrial applications.
PMID- 25131400
TI - Interactions between arbuscular mycorrhizal fungi and organic material
substrates.
AB - Arbuscular mycorrhizal (AM) associations are widespread and form between ca. two
thirds of all land plants and fungi in the phylum Glomeromycota. The association
is a mutualistic symbiosis with the fungi enhancing nutrient capture for the
plant while obtaining carbon in return. Although arbuscular mycorrhizal fungi
(AMF) lack any substantial saprophytic capability they do preferentially
associate with various organic substrates and respond by hyphal proliferation,
indicating the fungus derives a benefit from the organic substrate. AMF may also
enhance decomposition of the organic material. The benefit to the host plant of
this hyphal proliferation is not always apparent, particularly regarding nitrogen
(N) transfer, and there may be circumstances under which both symbionts compete
for the N released given both have a large demand for N. The results of various
studies examining AMF responses to organic substrates and the interactions with
other members of the soil community will be discussed.
PMID- 25131401
TI - Transcription regulation in the third domain.
AB - The ability of organisms to sense and respond to their environment is essential
to their survival. This is no different for members of the third domain of life,
the Archaea. Archaea are found in diverse and often extreme habitats. However,
their ability to sense and respond to their environment at the level of gene
expression has been understudied when compared to bacteria and eukaryotes. Over
the last decade, the field has expanded, and a variety of unique and interesting
regulatory schemes have been unraveled. In this review, the current state of
knowledge of archaeal transcription regulation is explored.
PMID- 25131402
TI - Bacteria-phage interactions in natural environments.
AB - Phages are considered the most abundant and diverse biological entities on Earth
and are notable not only for their sheer abundance, but also for their influence
on bacterial hosts. In nature, bacteria-phage relationships are complex and have
far-reaching consequences beyond particular pairwise interactions, influencing
everything from bacterial virulence to eukaryotic fitness to the carbon cycle. In
this review, we examine bacteria and phage distributions in nature first by
highlighting biogeographic patterns and nonhost environmental influences on phage
distribution, then by considering the ways in which phages and bacteria interact,
emphasizing phage life cycles, bacterial responses to phage infection, and the
complex patterns of phage host specificity. Finally, we discuss phage impacts on
bacterial abundance, genetics, and physiology, and further aim to clarify
distinctions between current theoretical models and point out areas in need of
future research.
PMID- 25131403
TI - The interactions of bacteria with fungi in soil: emerging concepts.
AB - In this chapter, we review the existing literature on bacterial-fungal
interactions in soil, exploring the role fungi may play for soil bacteria as
providers of hospitable niches. A focus is placed on the mycosphere, i.e., the
narrow zone of influence of fungal hyphae on the external soil milieu, in which
hypha-associated bacterial cells dwell. Evidence is brought forward for the
contention that the hyphae of both mycorrhizal and saprotrophic fungi serve as
providers of ecological opportunities in a grossly carbon-limited soil, as a
result of their release of carbonaceous compounds next to the provision of a
colonizable surface. Soil bacteria of particular nature are postulated to have
adapted to such selection pressures, evolving to the extent that they acquired
capabilities that allow them to thrive in the novel habitat created by the
emerging fungal hyphae. The mechanisms involved in the interactions and the modes
of genetic adaptation of the mycosphere dwellers are discussed, with an emphasis
on one key mycosphere-adapted bacterium, Burkholderia terrae BS001. In this
discussion, we interrogate the positive interactions between soil fungi and
bacteria, and refrain from considering negative interactions.
PMID- 25131404
TI - Production of specialized metabolites by Streptomyces coelicolor A3(2).
AB - The actinomycetes are well-known bioactive natural product producers, comprising
the Streptomycetes, the richest drug-prolific family in all kingdoms, producing
therapeutic compounds for the areas of infection, cancer, circulation, and
immunity. Completion and annotation of many actinomycete genomes has highlighted
further how proficient these bacteria are in specialized metabolism, which have
been largely underexploited in traditional screening programs. The genome
sequence of the model strain Streptomyces coelicolor A3(2), and subsequent
development of genomics-driven approaches to understand its large specialized
metabolome, has been key in unlocking the high potential of specialized
metabolites for natural product genomics-based drug discovery. This review
discusses systematically the biochemistry and genetics of each of the specialized
metabolites of S. coelicolor and describes metabolite transport processes for
excretion and complex regulatory patterns controlling biosynthesis.
PMID- 25131405
TI - Synthetic polyester-hydrolyzing enzymes from thermophilic actinomycetes.
AB - Thermophilic actinomycetes produce enzymes capable of hydrolyzing synthetic
polyesters such as polyethylene terephthalate (PET). In addition to
carboxylesterases, which have hydrolytic activity predominantly against PET
oligomers, esterases related to cutinases also hydrolyze synthetic polymers. The
production of these enzymes by actinomycetes as well as their recombinant
expression in heterologous hosts is described and their catalytic activity
against polyester substrates is compared. Assays to analyze the enzymatic
hydrolysis of synthetic polyesters are evaluated, and a kinetic model describing
the enzymatic heterogeneous hydrolysis process is discussed. Structure-function
and structure-stability relationships of actinomycete polyester hydrolases are
compared based on molecular dynamics simulations and recently solved protein
structures. In addition, recent progress in enhancing their activity and thermal
stability by random or site-directed mutagenesis is presented.
PMID- 25131406
TI - Characterization of robotic system passive path repeatability during specimen
removal and reinstallation for in vitro knee joint testing.
AB - Robotic testing systems are commonly utilized for the study of orthopaedic
biomechanics. Quantification of system error is essential for reliable use of
robotic systems. Therefore, the purpose of this study was to quantify a 6-DOF
robotic system's repeatability during knee biomechanical testing and characterize
the error induced in passive path repeatability by removing and reinstalling the
knee. We hypothesized removing and reinstalling the knee would substantially
alter passive path repeatability. Testing was performed on four fresh-frozen
cadaver knees. To determine repeatability and reproducibility, the passive path
was collected three times per knee following the initial setup (intra-setup), and
a single time following two subsequent re-setups (inter-setup). Repeatability was
calculated as root mean square error. The intra-setup passive path had a position
repeatability of 0.23 mm. In contrast, inter-setup passive paths had a position
repeatability of 0.89 mm. When a previously collected passive path was replayed
following re-setup of the knee, resultant total force repeatability across the
passive path increased to 28.2N (6.4N medial-lateral, 25.4N proximal-distal, and
10.5 N anterior-posterior). This study demonstrated that removal and re-setup of
a knee can have substantial, clinically significant changes on our system's
repeatability and ultimately, accuracy of the reported results.
PMID- 25131407
TI - Suppression of NGB and NAB/ERabp1 in tomato modifies root responses to potato
cyst nematode infestation.
AB - Plant-parasitic nematodes cause significant damage to major crops throughout the
world. The small number of genes conferring natural plant resistance and the
limitations of chemical control require the development of new protective
strategies. RNA interference or the inducible over-expression of nematicidal
genes provides an environment-friendly approach to this problem. Candidate genes
include NGB, which encodes a small GTP-binding protein, and NAB/ERabp1, which
encodes an auxin-binding protein, which were identified as being up-regulated in
tomato roots in a transcriptome screen of potato cyst nematode (Globodera
rostochiensis) feeding sites. Real-time reverse transcription-polymerase chain
reaction (RT-PCR) and in situ hybridization confirmed the localized up-regulation
of these genes in syncytia and surrounding cells following nematode infection.
Gene-silencing constructs were introduced into tomato, resulting in a 20%-98%
decrease in transcription levels. Nematode infection tests conducted on
transgenic plants showed 57%-82% reduction in the number of G. rostochiensis
females in vitro and 30%-46% reduction in pot trials. Transmission electron
microscopy revealed a deterioration of cytoplasm, and degraded mitochondria and
plastids, in syncytia induced in plants with reduced NAB/ERabp1 expression.
Cytoplasm in syncytia induced in plants with low NGB expression was strongly
electron translucent and contained very few ribosomes; however, mitochondria and
plastids remained intact. Functional impairments in syncytial cytoplasm of
silenced plants may result from NGB's role in ribosome biogenesis; this was
confirmed by localization of yellow fluorescent protein (YFP)-labelled NGB
protein in nucleoli and co-repression of NGB in plants with reduced NAB/ERabp1
expression. These results demonstrate that NGB and NAB/ERabp1 play important
roles in the development of nematode-induced syncytia.
PMID- 25131408
TI - Exit strategy for unmappable VT?
PMID- 25131410
TI - Low capping group surface density on zinc oxide nanocrystals.
AB - The ligand shell of colloidal nanocrystals can dramatically affect their
stability and reaction chemistry. We present a methodology to quantify the
dodecylamine (DDA) capping shell of colloidal zinc oxide nanocrystals in a
nonpolar solvent. Using NMR spectroscopy, three different binding regimes are
observed: strongly bound, weakly associated, and free in solution. The surface
density of bound DDA is constant over a range of nanocrystal sizes, and is low
compared to both predictions of the number of surface cations and maximum
coverages of self-assembled monolayers. The density of strongly bound DDA ligands
on the as-prepared ZnO NCs is 25% of the most conservative estimate of the
maximum surface DDA density. Thus, these NCs do not resemble the common picture
of a densely capped surface ligand layer. Annealing the ZnO NCs in molten DDA for
12 h at 160 degrees C, which is thought to remove surface hydroxide groups,
resulted in a decrease of the weakly associated DDA and an increase in the
density of strongly bound DDA, to ca. 80% of the estimated density of a self
assembled monolayer on a flat ZnO surface. These findings suggest that as
prepared nanocrystal surfaces contain hydroxide groups (protons on the ZnO
surfaces) that inhibit strong binding of DDA.
PMID- 25131409
TI - The effect of obesity and type 1 diabetes on renal function in children and
adolescents.
AB - BACKGROUND: Early signs of renal complications can be common in youths with type
1 diabetes (T1D). Recently, there has been an increasing interest in potential
renal complications associated with obesity, paralleling the epidemics of this
condition, although there are limited data in children. HYPOTHESIS: Obese
children and adolescents present signs of early alterations in renal function
similar to non-obese peers with T1D. SUBJECTS: Eighty-three obese (age: 11.6 +/-
3.0 yr), 164 non-obese T1D (age: 12.4 +/- 3.2 yr), and 71 non-obese control (age:
12.3 +/- 3.2 yr) children and adolescents were enrolled in the study. METHODS:
Anthropometric parameters and blood pressure were measured. Renal function was
assessed by albumin excretion rate (AER), serum cystatin C, creatinine and
estimated glomerular filtration rate (e-GFR), calculated using the Bouvet's
formula. RESULTS: Obese and non-obese T1D youths had similar AER [8.9(5.9-10.8)
vs. 8.7(5.9-13.1) ug/min] and e-GFR levels (114.8 +/- 19.6 vs. 113.4 +/- 19.1
mL/min), which were higher than in controls [AER: 8.1(5.9-8.7) ug/min, e-GFR:
104.7 +/- 18.9 mL/min]. Prevalence of microalbuminuria and hyperfiltration was
similar between obese and T1D youths and higher than their control peers (6.0 vs.
8.0 vs. 0%, p = 0.02; 15.9 vs. 15.9 vs. 4.3%, p = 0.03, respectively). Body mass
index (BMI) z-score was independently related to e-GFR (r = 0.328; p < 0.001),
and AER (r = 0.138; p = 0.017). Hemoglobin A1c (HbA1c) correlated with AER (r =
0.148; p = 0.007) but not with eGFR (r = 0.041; p = 0.310). CONCLUSIONS: Obese
children and adolescents show early alterations in renal function, compared to
normal weight peers, and they have similar renal profiles than age-matched peers
with T1D.
PMID- 25131411
TI - Defining the biology component of the drug discovery strategy for malaria
eradication.
AB - Malaria is still considered a deadly scourge in Africa, Asia, and South America
despite improved vector control and curative treatments with new antimalarial
combinations. The next challenge is to work towards disease eradication. To
achieve this goal it is crucial to develop, validate, and integrate biological
assays into test cascades that align with the key target product profiles. For
anti-relapse, a parent molecule should kill hypnozoites or cause activation of
Plasmodium vivax liver stages. For transmission blocking, dual equal-activity
antimalarials killing both the asexual and the sexual parasite stages in human
blood are favored. Finally, by assessing cross resistance and generating drug
resistance in the laboratory, it is expected that new medicines with acceptable
resistance profiles will be forthcoming.
PMID- 25131412
TI - Lesions to the CA2 region of the hippocampus impair social memory in mice.
AB - The function of the CA2 region of the hippocampus is poorly understood. Although
the CA1 and CA3 regions have been extensively studied, for years the CA2 region
has primarily been viewed as a linking area between the two. However, the CA2
region is known to have distinct neurochemical and structural features that are
different from the other parts of the hippocampus and in recent years it has been
suggested that the CA2 region may play a role in the formation and/or recall of
olfactory-based memories needed for normal social behavior. Although this
hypothesis has been supported by hippocampal lesion studies that have included
the CA2 region, no studies have attempted to specifically lesion the CA2 region
of the hippocampus in mice to determine the effects on social recognition memory
and olfaction. To fill this knowledge gap, we sought to perform excitotoxic N
methyl-D-aspartate lesions of the CA2 region and determine the effects on social
recognition memory. We predicted that lesions of the CA2 region would impair
social recognition memory. We then went on to test olfaction in CA2-lesioned
mice, as social memory requires a functional olfactory system. Consistent with
our prediction, we found that CA2-lesioned animals had impaired social
recognition. These findings are significant because they confirmed that the CA2
region of the hippocampus is a part of the neural circuitry that regulates social
recognition memory, which may have implications for our understanding of the
neural regulation of social behavior across species.
PMID- 25131413
TI - Pilot study of an oral care protocol on poststroke survivors.
AB - PURPOSE: The pilot study purpose was to determine the effects of a new
standardized oral care protocol (intervention) to usual care practices (control)
in poststroke patients. DESIGN: This study is a randomized controlled clinical
trial. METHOD: Fifty-one subjects were enrolled. Subjects in the intervention
group received oral care twice a day including tooth brushing, tongue brushing,
flossing, mouth rinse, and lip care while control patients received usual oral
care. FINDINGS: Subjects in the control and intervention groups showed
improvement in their oral health assessments, swallowing abilities and oral
intake. There were no significant differences between the two groups. Although
not statistically significant, overall prevalence of methicillin-resistant
Staphylococcus aureus and methicillin-sensitive Staphylococcus aureus
colonization in the control group almost doubled (from 4.8% to 9.5%), while
colonization in the intervention group decreased (from 20.8% to 16.7%).
CONCLUSIONS/CLINICAL RELEVANCE: These findings demonstrate the importance of oral
care in the poststroke patient with dysphagia.
PMID- 25131414
TI - Comparison of conventional freezing and vitrification with dimethylformamide and
ethylene glycol for cryopreservation of ovine embryos.
AB - The aim of this work was to evaluate the efficiency of the cryoprotectants
dimethylformamide and ethylene glycol for cryopreservation of ovine embryos using
vitrification and conventional freezing. The recovered embryos were distributed
randomly in three treatment groups: Gr. 1: conventional freezing (n = 44), Gr. 2:
vitrification with ethylene glycol (n = 39) and Gr. 3: vitrification with
dimethylformamide (n = 38). Quality of fresh embryos in control group as well as
of frozen and vitrified embryos was examined by three methodologies: staining
with propidium iodide and Hoechst 33258 and evaluation under fluorescent
microscopy, evaluation of re-expansion and hatching rates after culture, and
determination of apoptotic index with TUNEL technique. It was established that re
expansion rate in all treatment groups was similar. In the same time, hatching
rates were higher in Gr. 1 (40.5%) and Gr. 2 (35.3%) in comparison with Gr. 3
(15.5%, p < 0.05). The number of dead cells in vitrified embryos of Gr. 2 and Gr.
3 was higher (42.6 +/- 26.2 and 63.2 +/- 34.65, respectively) in comparison with
Gr. 1 (conventional freezing, 10.1 +/- 8.5, p < 0.05). Embryos vitrified with
dimethylformamide included the same quality of apoptotic cells that Gr. 1
(conventional freezing) and fresh embryos. In conclusion, the dimethylformamide
and ethylene glycol used as cryoprotectant to vitrify ovine embryos, in the
concentrations and exposition time tested in this work, were not as efficient as
the conventional freezing for cryopreservation of ovine embryos Thus, the
conventional freezing with ethylene glycol was the most efficient method to
cryopreserve ovine embryos in comparison with vitrification.
PMID- 25131415
TI - Pneumocystis jirovecii pneumonia in patients with end-stage renal disease: a
comparison with the general population.
AB - BACKGROUND: Data on occurrence and risk factors for pneumocystis pneumonia (PCP)
in patients with end-stage renal disease (ESRD) are sparse. METHODS: This was a
nationwide population-based study assessing occurrence and risk factors for PCP
among patients with ESRD and population controls over a 21-year period (1/1 1990
to 31/12 2010). Using Danish registry data, first-time diagnoses of PCP were
identified. RESULTS: We identified 13 296 adult patients with ESRD and 244 255
controls, yielding 63 560 and 2 223 660 person-years of follow-up (PYFU),
respectively. Fifty-eight first-time diagnoses of PCP were recorded in the ESRD
group. Forty-six episodes occurred among renal transplant recipients (RTx) and 12
among haemodialysis patients (HD), yielding incidence rates of 181 (136-242) and
43.1 (24.5-75.9) per 100 000 PYFU. Compared to population controls, we found
incidence rate-ratios of 125.9 (78.4-204) among RTx and 29.9 (14.1-59.7) among HD
patients. Risk factors for PCP in RTx were age 50-65 years, age > 65 years,
diabetes, polycystic kidney disease and hypertensive kidney
disease/nephrosclerosis with an IRR of 2.22 (1.14-4.31), 3.12 (1.35-7.21), 3.44
(1.16-10.2), 4.25 (1.55-11.7) and 3.87 (1.49-10.0), respectively, and more than
36 months of dialysis before transplantation with an IRR of 1.99 (1.03-3.84).
Among RTx the risk of PCP was highest during the first 6 months post
transplantation and increased from the beginning (IR1990-94 = 111 (46.3-267) per
100 000 PYFU) towards the end of the study period (IR2005-10 = 299 (203-439)).
CONCLUSION: The PCP risk is substantial in RTx within the first 6 months of
transplantation, emphasizing the potential benefit of prophylactic treatment in
the early post-transplant period. Importantly, we identified subgroups within the
RTx group that require more attention.
PMID- 25131416
TI - Interface-induced nonswitchable domains in ferroelectric thin films.
AB - Engineering domains in ferroelectric thin films is crucial for realizing
technological applications including non-volatile data storage and solar energy
harvesting. Size and shape of domains strongly depend on the electrical and
mechanical boundary conditions. Here we report the origin of nonswitchable
polarization under external bias that leads to energetically unfavourable head-to
head domain walls in as-grown epitaxial PbZr(0.2)Ti(0.8)O3 thin films. By mapping
electrostatic potentials and electric fields using off-axis electron holography
and electron-beam-induced current with in situ electrical biasing in a
transmission electron microscope, we show that electronic band bending across
film/substrate interfaces locks local polarization direction and further produces
unidirectional biasing fields, inducing nonswitchable domains near the interface.
Presence of oxygen vacancies near the film surface, as revealed by electron
energy loss spectroscopy, stabilizes the charged domain walls. The formation of
charged domain walls and nonswitchable domains reported in this study can be an
origin for imprint and retention loss in ferroelectric thin films.
PMID- 25131417
TI - Cover versus recovery: contrasting responses of two indicators in seagrass beds.
AB - Despite being a highly valuable key-stone ecosystem, seagrass meadows are
threatened and declining worldwide, creating urgent need for indicators of their
health status. We compared two indicators for seagrass health: standing leaf area
index versus relative recovery from local disturbance. Disturbance was created by
removing aboveground biomass and recording the rate of regrowth for Zostera
marina meadows exposed to contrasting wave regimes and nutrient stress levels.
Within the experimental period, relative regrowth in gaps was around 50% in most
plots, except for the ambient nutrient treatment at the sheltered site, where it
exceeded 100%. The two indicators showed an opposite response to disturbance: the
higher the standing leaf area index, the lower the relative recovery from
disturbance. This conflicting response raises the question on the proper
interpretation of such indicators to estimate seagrass health and resilience, and
how to ideally monitor seagrass ecosystems in order to predict collapse.
PMID- 25131418
TI - Marine debris is selected as nesting material by the brown booby (Sula
leucogaster) within the Swain Reefs, Great Barrier Reef, Australia.
AB - Many seabirds are impacted by marine debris through its presence in foraging and
nesting areas. To determine the extent of this problem, marine debris use in nest
material of the brown booby (Sula leucogaster) in the Great Barrier Reef,
Australia, was investigated. Nine cays were examined using beach and nest
surveys. On average, four marine debris items were found per nest (n=96) with
58.3% of surveyed nests containing marine debris. The source of marine debris in
nests and transects were primarily oceanic. Hard plastic items dominated both
nest (56.8%) and surveyed beaches (72.8%), however only two item types were
significantly correlated between these surveys. Nest surveys indicated higher
levels of black and green items compared to beach transects. This selectivity for
colours and items suggest these nests are not good indicators of environmental
loads. This is the first study to examine S. leucogaster nests for marine debris
in this location.
PMID- 25131419
TI - Vertical distribution and source identification of polycyclic aromatic
hydrocarbons (PAHs) in southwest of the Caspian Sea: most petrogenic events
during the late Little Ice Age.
AB - In this study, 75 samples of two (210)Pb-dated cores from the southwest of the
Caspian Sea were analysed for 30 compounds of polycyclic aromatic hydrocarbons
(PAHs). The TPAH29 flux of the last six centuries ranged from 16.3 to 177.3 and
22.3 to 426.2 ng cm(-2)y(-1) in the Rezvanshahr and Anzali core sediments,
respectively. Prior to 1840, four distinct maxima in PAH fluxes (61-426.2 ng cm(
2)y(-1)) with a low weathered petrogenic pattern were found in each of the core
sediments. Simultaneity of distinct peaks of PAH fluxes before 1840 and Caspian
Sea level high-stands during the Little Ice Age (LIA), revealed the high
importance of this phenomenon in washing and transport of land-based oil
pollution into the Caspian Sea. An overall increase in some diagnostic ratios
(Flu/202, IP/276 and BaA/228), especially after 1940, indicated increase of
pyrogenic PAHs as a result of industrial development in the catchment area.
PMID- 25131420
TI - Sources and preservation of sedimentary organic matter in the Southern Bohai Sea
and the Yellow Sea: evidence from lipid biomarkers.
AB - The region of Southern Bohai Sea (SBS) and Yellow Sea (YS) represents one of the
best examples of large river-dominated ocean margins. The transport and
accumulation of sediments played a primary role in distribution of the lipids in
the region and could lead to a preferential accumulation of these more refractory
land-based lipids. The spatial distribution of total organic carbon (TOC) matched
with the lipid distributions over the shelf, and high TOC presented in the
central YS, but TOC burial fluxes decreased from 110 ton/km(2)/yr of SBS to 25-32
ton/km(2)/yr of YS. Good correlations were observed between terrestrial n-alkanes
and TOC in the sediments of SBS and northern YS, but they were poor for southern
YS, meanwhile higher ratios of nC27+nC29+nC31/nC15+nC17+nC19 (12+/-6) were
observed in SBS, and lower in YS (2.2+/-1.0), suggesting the Yellow River
discharge was an important source of terrestrial organic matter to the shelf.
PMID- 25131422
TI - Writing and functionalisation of suspended DNA nanowires on superhydrophobic
pillar arrays.
AB - Nanowire arrays and networks with precisely controlled patterns are very
interesting for innovative device concepts in mesoscopic physics. In particular,
DNA templates have proven to be versatile for the fabrication of complex
structures that obtained functionality via combinations with other materials, for
example by functionalisation with molecules or nanoparticles, or by coating with
metals. Here, the controlled motion of the a three-phase contact line (TCL) of
DNA-loaded drops on superhydrophobic substrates is used to fabricate suspended
nanowire arrays. In particular, the deposition of DNA wires is imaged in situ,
and different patterns are obtained on hexagonal pillar arrays by controlling the
TCL velocity and direction. Robust conductive wires and networks are achieved by
coating the wires with a thin layer of gold, and as proof of concept conductivity
measurements are performed on single suspended wires. The plastic material of the
superhydrophobic pillars ensures electrical isolation from the substrate. The
more general versatility of these suspended nanowire networks as functional
templates is outlined by fabricating hybrid organic-metal-semiconductor nanowires
by growing ZnO nanocrystals onto the metal-coated nanowires.
PMID- 25131423
TI - Mycobacterium tuberculosis Secreted Proteins As Potential Biomarkers for the
Diagnosis of Active Tuberculosis and Latent Tuberculosis Infection.
AB - BACKGROUND: The detection of Mycobacterium tuberculosis (Mtb) specific human
antibodies has been an important diagnostic aid in the diagnosis of tuberculosis
(TB) cases with smear-negative sputum samples, especially for the screening of
high-risk population. This study focused on the analysis and comparison of the
four potential Mtb-secreted proteins (ESAT6, CFP10, Ag85B, Hsp16.3) and the
fusion protein Ag85B-Hsp16.3 as new markers in the serodiagnosis between active
TB and latent TB infection (LTBI). METHODS: These five recombinant proteins were
produced and used in optimized ELISA to detect IgG serum antibodies against the
four secreted proteins. The capacity of identifying infection was evaluated
either in active TB patients or LTBI individuals, which was compared with the
control groups consisting of hospitalized non-TB individuals. RESULTS: The
results showed that Ag85B-Hsp16.3/ESAT6 and Hsp16.3/ESAT6 were the best
associated antigens for serology diagnosis of the active TB and LTBI individuals
because of their specificity, sensitivity, YI values, and positive rates,
respectively. ELISA test demonstrated that 41.67% (25/60) of blood donors respond
to Ag85B-Hsp16.3/ESAT6. The consistency of this positive respond with clinical
diagnosis almost reached 84% (21/25). CONCLUSION: Thus, a combined test of
multiple Mtb-secreted proteins Ag85B, Hsp16.3, and ESAT6 may be the ascendant
preliminary screening antigens for active TB or LTBI patients.
PMID- 25131424
TI - Current update of chemomechanical caries removal methods.
AB - Chemomechanical caries removal is an excellent method for minimally invasive
caries excavation, and the removal agents are either sodium hypochlorite (NaOCl)-
or enzyme-based. The NaOCl-based agents include GK-101, GK-101E (Caridex) and
Carisolv, and the enzyme-based agents include Papacarie and the experimental
material, Biosolv. This review outlines the changes in chemomechanical caries
removal methods and focuses on recently published laboratory and clinical
studies. The historical development, mechanism of action, excavation time and
biological effects on pulp and dental hard tissues are described. Based on
existing evidence, the currently available chemomechanical caries removal methods
are viable alternatives to conventional rotary instrument methods.
Chemomechanical methods could be extremely useful in very anxious, disabled and
paediatric patients. It does seem some of these agents would still benefit from
quicker excavation times in order to achieve more universal acceptance. However,
as a means of conserving the caries-affected dentine, chemomechanical caries
removal is possibly much more successful than conventional rotary
instrumentation.
PMID- 25131421
TI - Single-cell genetic analysis reveals insights into clonal development of prostate
cancers and indicates loss of PTEN as a marker of poor prognosis.
AB - Gauging the risk of developing progressive disease is a major challenge in
prostate cancer patient management. We used genetic markers to understand genomic
alteration dynamics during disease progression. By using a novel, advanced,
multicolor fluorescence in situ hybridization approach, we enumerated copy
numbers of six genes previously identified by array comparative genomic
hybridization to be involved in aggressive prostate cancer [TBL1XR1, CTTNBP2, MYC
(alias c-myc), PTEN, MEN1, and PDGFB] in six nonrecurrent and seven recurrent
radical prostatectomy cases. An ERG break-apart probe to detect TMPRSS2-ERG
fusions was included. Subsequent hybridization of probe panels and cell
relocation resulted in signal counts for all probes in each individual cell
analyzed. Differences in the degree of chromosomal and genomic instability (ie,
tumor heterogeneity) or the percentage of cells with TMPRSS2-ERG fusion between
samples with or without progression were not observed. Tumors from patients that
progressed had more chromosomal gains and losses, and showed a higher degree of
selection for a predominant clonal pattern. PTEN loss was the most frequent
aberration in progressers (57%), followed by TBL1XR1 gain (29%). MYC gain was
observed in one progresser, which was the only lesion with an ERG gain, but no
TMPRSS2-ERG fusion. According to our results, a probe set consisting of PTEN,
MYC, and TBL1XR1 would detect progressers with 86% sensitivity and 100%
specificity. This will be evaluated further in larger studies.
PMID- 25131425
TI - Dissolution-enhanced luminescent bioassay based on inorganic lanthanide
nanoparticles.
AB - Conventional dissociation-enhanced lanthanide fluoroimmunoassays (DELFIA) using
molecular probes suffer from a low labeling ratio of lanthanide ions (Ln(3+) )
per biomolecule. Herein, we develop a unique bioassay based on the dissolution
enhanced luminescence of inorganic lanthanide nanoparticles (NPs). As a result of
the highly concentrated Ln(3+) ions in a single Ln(3+) NP, an extremely high
Ln(3+) labeling ratio can be achieved, which amplifies significantly the
luminescence signal and thus improves the detection sensitivity compared to
DELFIA. Utilizing sub-10 nm NaEuF4 NPs as dissolution-enhanced luminescent
nanoprobes, we demonstrate the successful in vitro detection of carcinoembryonic
antigen (CEA, an important tumor marker) in human serum samples with a record-low
detection limit of 0.1 pg mL(-1) (0.5 fM). This value is an improvement of
approximately 3 orders of magnitude relative to that of DELFIA. The dissolution
enhanced luminescent bioassay shows great promise in versatile bioapplications,
such as ultrasensitive and multiplexed in vitro detection of disease markers in
clinical diagnosis.
PMID- 25131426
TI - Construction and evaluation of a genetic construct for specific detection and
measurement of propionate by whole-cell bacteria.
AB - Anaerobic digestion is a microbiological technology that converts biomass wastes
into biogas, achieving both waste treatment and bioenergy production.
Accumulation of volatile fatty acids (VFA) during acidogenesis, particularly
propionate, often causes upset or failure of digesters. Early detection and
monitoring of propionate concentration in digesters allow for just-in-time
interventions to prevent irreversible costly process breakdown. In an attempt to
develop a rapid method of measuring propionate concentration and bioavailability,
we constructed a genetic construct for specific detection of bioavailable
propionate. The genetic construct was constructed by transcriptional fusion of
the regulatory gene (prpR) and the promoter of the prp operon (PprpB ) of
Escherichia coli W3110 with the reporter gene cassette luxCDABE. When the genetic
construct was carried on a plasmid and transformed into E. coli (referred to as
plasmid-based biosensor), it resulted in stronger emission of luminescence than
when it was inserted into the chromosome of E. coli (referred to as chromosome
based biosensor). The biosensor responded specifically to propionate. The
luminescence signal increased linearly with increasing concentration of
propionate from 1 to 10 mM. The utility of the biosensor was evaluated using
samples collected from anaerobic digesters. Once instrumented in future studies,
the whole-cell bacterial biosensor developed in this study may provide an
alternative technology for real-time detection and measurement of propionate in
digesters.
PMID- 25131427
TI - High doses of benzodiazepine predict analgesic and sedative drug withdrawal
syndrome in paediatric intensive care patients.
AB - AIM: Critically ill children can develop withdrawal syndrome after prolonged
analgesia and sedation in a paediatric intensive care unit (PICU), when treatment
is stopped abruptly or reduced quickly. The aim of this study was to evaluate the
incidence of withdrawal syndrome in patients after three or more days of
analgesic or sedative drug therapy, using a validated scale. We also analysed the
association between withdrawal syndrome and the patients' outcome and factors
related to analgesia and sedation treatment. METHODS: This prospective
observational study analysed 89 periods of weaning from analgesia and sedation in
60 children between October 2010 and October 2011. Of these, 65% were less than
six months old and 45% were admitted to the PICU after heart surgery. Withdrawal
syndrome was assessed using the Withdrawal Assessment Tool-1 (WAT-1) scale.
RESULTS: The incidence of withdrawal syndrome was 37%, and the only variable that
predicted its presence was the highest administered dose of benzodiazepine. The
duration of weaning, Sophia Observational Withdrawal Symptom scale score and
nurse judgment were also associated with positive WAT-1 scores. CONCLUSION:
Withdrawal syndrome should be considered after three or more days of analgesic or
sedative treatment. A high dose of benzodiazepine increases the risk of
developing withdrawal symptoms.
PMID- 25131428
TI - Pharmacokinetic modeling and Monte Carlo simulation of ondansetron following oral
administration in dogs.
AB - Ondansetron is a potent antiemetic drug that has been commonly used to treat
acute and chemotherapy-induced nausea and vomiting (CINV) in dogs. The aim of
this study was to perform a pharmacokinetic analysis of ondansetron in dogs
following oral administration of a single dose. A single 8-mg oral dose of
ondansetron (Zofran((r)) ) was administered to beagles (n = 18), and the plasma
concentrations of ondansetron were measured by liquid chromatography-tandem mass
spectrometry. The data were analyzed by modeling approaches using ADAPT5, and
model discrimination was determined by the likelihood-ratio test. The peak plasma
concentration (Cmax ) was 11.5 +/- 10.0 ng/mL at 1.1 +/- 0.8 h. The area under
the plasma concentration vs. time curve from time zero to the last measurable
concentration was 15.9 +/- 14.7 ng.h/mL, and the half-life calculated from the
terminal phase was 1.3 +/- 0.7 h. The interindividual variability of the
pharmacokinetic parameters was high (coefficient of variation > 44.1%), and the
one-compartment model described the pharmacokinetics of ondansetron well. The
estimated plasma concentration range of the usual empirical dose from the Monte
Carlo simulation was 0.1-13.2 ng/mL. These findings will facilitate determination
of the optimal dose regimen for dogs with CINV.
PMID- 25131429
TI - Development and evaluation of the Stages of Change in Oral Health instrument.
AB - OBJECTIVES: Oral health personnel are limited in their ability to assess the
readiness of patients to make changes to improve oral health. We aimed to develop
and test the Stages of Change in Oral Health (SOCOH) model, a scaled index of the
stages of change - pre-contemplative, contemplative or active - with particular
emphasis on pregnancy. MATERIALS AND METHODS: Items were collected in a self
report questionnaire conducted among a convenience sample of 446 mothers (age
range: 14-43 years) pregnant with Aboriginal children in South Australia,
Australia. Scales representing openness (four items; Cronbach's alpha = 0.73),
value (four items; Cronbach's alpha = 0.71), inconvenience (six items; Cronbach's
alpha = 0.79) and permissiveness (four items; Cronbach's alpha = 0.66) were
developed. Participants were categorised according to the Stages of Change model
and were evaluated against key self-reported oral health outcomes. RESULTS: Some
11.9% of participants were classified as pre-contemplators, 46.4% as
contemplators and 41.7% as active. A higher proportion of active participants had
a higher education, last visited a dentist less than a year previously, had no
dental fear, owned a toothbrush, brushed the previous day, used toothpaste, had
no difficulties paying a $100 dental bill, self-reported their dental health as
'excellent' and in the previous 12 months did not experience dental pain,
embarrassment related to their dental appearance or difficulties eating food.
CONCLUSIONS: The SOCOH model offers an internally consistent and valid instrument
for detailed assessment of the readiness for change in regarding oral health
behaviours in pregnancy and has potential benefits for clinical decision making
and research.
PMID- 25131430
TI - Anticonvulsants to treat post-traumatic stress disorder.
AB - OBJECTIVE: We reviewed the existing literature on the efficacy of anticonvulsants
in treating post-traumatic stress disorder. METHODS: We performed a literature
search using PubMed, EMBASE and the Cochrane database on 30 September 2013.
Randomized,controlled studies that investigated the efficacy of anticonvulsants
for post-traumatic stress disorder were included in this review. Studies with
retrospective designs, case reports and case series were excluded. RESULTS: A
total of seven studies met the inclusion criteria for this review. Three studies
used topiramate with negative findings regarding its efficacy. Two studies used
divalproex, both of which failed to show superiority over placebo. One study used
lamotrigine, with favourable results, and one study used tiagabine, with negative
results. CONCLUSIONS: Future long-term studies with larger sample sizes are
needed to investigate the clinical utility of anticonvulsants for posttraumatic
stress disorder treatment.
PMID- 25131431
TI - [Allopurinol and its role in the treatment of sarcopenia].
AB - Xanthine oxidase (XO) is an enzyme that catalyzes the oxidation of hypoxanthine
to xanthine and uric acid and plays an important role in purine catabolism. The
purine analogue, allopurinol, is a well-known inhibitor of XO widely used in the
clinical management of gout and conditions associated with hyperuricemia. More
recent data indicate that allopurinol reduces oxidative stress and improves
vascular function in several cardiometabolic diseases, prolongs exercise time in
angina, and improves the efficiency of cardiac contractility in heart failure. XO
also plays an important role in free radical generation during skeletal muscle
contraction and thus, it has been related to the muscle damage associated to
exhaustive exercise. Several research groups have shown the protective effect of
allopurinol in the prevention of this type of damage. Based on this background, a
critical overview is presented on the possible role of allopurinol in the
treatment of sarcopenia, a geriatric syndrome characterized by progressive and
generalized loss of skeletal muscle mass and strength with a risk of adverse
outcomes, such as physical disability, poor quality of life and death.
PMID- 25131432
TI - Body size evolution in Titanosauriformes (Sauropoda, Macronaria).
AB - Titanosauriformes is a conspicuous and diverse group of sauropod dinosaurs that
inhabited almost all land masses during Cretaceous times. Besides the diversity
of forms, the clade comprises one of the largest land animals found so far,
Argentinosaurus, as well as some of the smallest sauropods known to date,
Europasaurus and Magyarosaurus. They are therefore good candidates for studies on
body size trends such as the Cope's rule, the tendency towards an increase in
body size in an evolutionary lineage. We used statistical methods to assess body
size changes under both phylogenetic and nonphylogenetic approaches to identify
body size trends in Titanosauriformes. Femoral lengths were collected (or
estimated from humeral length) from 46 titanosauriform species and used as a
proxy for body size. Our findings show that there is no increase or decrease in
titanosauriform body size with age along the Cretaceous and that negative changes
in body size are more common than positive ones (although not statistically
significant) for most of the titanosauriform subclades (e.g. Saltasaridae,
Lithostrotia, Titanosauria and Somphospondyli). Therefore, Cope's rule is not
supported in titanosauriform evolution. Finally, we also found a trend towards a
decrease of titanosauriform mean body size coupled with an increase in body size
standard deviation, both supporting an increase in body size variation towards
the end of Cretaceous.
PMID- 25131433
TI - Involvement of NLRP3 inflammasome in rituximab-induced interstitial lung disease:
a case report.
AB - WHAT IS KNOWN AND OBJECTIVE: Rituximab is a chimeric anti-CD20 IgG1 monoclonal
antibody for the treatment of various forms of lymphoma and haematological
autoimmune diseases. Interstitial lung disease is a rare but lethal pulmonary
toxicity of rituximab. Nod-like receptor pyrin domain-containing protein 3
(NLRP3) inflammasome is a molecular platform activated upon signs of cellular
'danger' to trigger the maturation of pro-inflammatory cytokines. We report the
first case of rituximab-induced interstitial lung disease (R-ILD) with NLRP3
inflammasome activation in the lung. CASE SUMMARY: A 30-year-old male patient
diagnosed with idiopathic thrombocytopenic purpura (ITP) was treated with four
cycles of rituximab in one month. Three weeks after last rituximab
administration, he developed progressive dyspnoea associated with respiratory
failure, which was diagnosed as R-ILD. The patient showed a good response to
steroid treatment, and lung biopsy was performed 5 days after the treatment.
Immunohistopathological studies of lung specimens showed high expressions of
inflammasome components NLRP3, apoptosis-associated speck-like protein containing
a caspase recruitment domain (ASC) and caspase-1 in lung interstitium with a
heavy infiltration of CD19-positive cells. The levels of inflammasome-related
cytokines IL-1beta and IL-18 in the serum were declined during the therapy. WHAT
IS NEW AND CONCLUSIONS: This is the first report confirmed the role of NLRP3
inflammasome in pulmonary toxicity of rituximab. Inhibited activation of NLRP3
inflammasome in lung by steroid treatment could reverse R-ILD and block
subsequent lung fibrosis. This result could open a new sight into the
pathogenesis and provide a new target for the treatment of R-ILD.
PMID- 25131437
TI - Alterations in collagen fibre patterns in breast cancer. A premise for tumour
invasiveness?
AB - Stromal tissue in the breast plays a key role in cancer invasiveness due to
molecular and cellular changes. Collagen is the main component of the stroma. The
purposes of this study were to investigate differences in collagen fibre patterns
between tumour-induced stromal tissue and normal stroma, and between high-grade
and low-grade breast cancer stroma, using second harmonic generation microscopy.
Thirty-seven ductal carcinomas were examined: Twenty-one Luminal A phenotype and
sixteen HER2 or Basal-like phenotype. Three regions were examined in each case:
intratumoral, juxtatumoral and extratumoral. Two images were captured in each
region. Two characteristics of collagen fibres were examined: the degree of
straightness, and the degree of alignment. Collagen fibres were visually
classified as curly, intermediate or straight, and as parallel or not parallel.
The results of angle measurement and visual analysis showed that collagen fibres
were straightest in the intratumoral region and curliest in the extratumoral
region. Collagen fibres were more parallel in the juxtatumoral region compared to
the two other regions. There were no significant differences between high-grade
and low-grade tumours. As a breast tumour progresses, collagen fibres appear to
straighten and align at the tumour boundary. This could facilitate invasion of
the tumour into the surrounding stroma.
PMID- 25131436
TI - Regulation of fatty acid biosynthesis by the global regulator CcpA and the local
regulator FabT in Streptococcus mutans.
AB - SMU.1745c, encoding a putative transcriptional regulator of the MarR family, maps
to a location proximal to the fab gene cluster in Streptococcus mutans. Deletion
of the SMU.1745c (fabTS m ) coding region resulted in a membrane fatty acid
composition comprised of longer-chained, unsaturated fatty acids (UFA), compared
with the parent strain. Previous reports have indicated a role for FabT in
regulation of genes in the fab gene cluster in other organisms, through binding
to a palindromic DNA sequence. Consensus FabT motif sequences were identified in
S. mutans in the intergenic regions preceding fabM, fabTSm and fabK in the fab
gene cluster. Chloramphenicol acetyltransferase (cat) reporter fusions, using the
fabM promoter, revealed elevated transcription in a ?fabTS m background.
Transcription of fabTS m was dramatically elevated in cells grown at pH values of
5 and 7 in the ? fabTS m background. Transcription of fabTS m was also elevated
in a strain carrying a deletion for the carbon catabolite repressor CcpA.
Purified FabTS m and CcpA bound to the promoter regions of fabTS m and fabM.
Hence, the data indicate that FabTS m acts as a repressor of fabM and fabTS m
itself and the global regulator CcpA acts as a repressor for fabTS m .
PMID- 25131439
TI - The effect of calcium phosphate composite scaffolds on the osteogenic
differentiation of rabbit dental pulp stem cells.
AB - The objective of this study is to compare the effects of the two calcium
phosphate composite scaffolds on the attachment, proliferation, and osteogenic
differentiation of rabbit dental pulp stem cells (DPSCs). One nano
hydroxyapatite/collagen/poly (l-lactide) (nHAC/PLA), imitating the composition
and the micro-structure characteristics of the natural bone, was made by Beijing
Allgens Medical Science & Technology Co., Ltd. (China). The other beta-tricalcium
phosphate (beta-TCP), being fully interoperability globular pore structure, was
provided by Shanghai Bio-lu Biomaterials Co, Ltd. (China). We compared the
absorption water rate and the protein adsorption rate of two scaffolds and the
characterization of DPSCs cultured on the culture plate and both scaffolds under
osteogenic differentiation media (ODM) treatment. The constructs were then
implanted subcutaneously into the back of severely combined immunodeficient
(SCID) mice for 8 and 12 weeks to compare their bone formation capacity. The
results showed that the ODM-treated DPSCs expressed osteocalcin (OCN), bone
sialoprotein (BSP), type I collagen (COLI) and osteopontin (OPN) by
immunofluorescence staining. Positive alkaline phosphatase (ALP) staining,
calcium deposition and calcium nodules were also observed on the ODM-treated
DPSCs. The absorption water rate and protein adsorption rate of nHAC/PLA was
significantly higher than beta-TCP. The initial attachment of DPSCs seeded onto
nHAC/PLA was significantly higher than that onto beta-TCP; and the proliferation
rate of the cells was also significantly higher than that of beta-TCP on 1, 3,
and 7 days of cell culture. The ALP activity, calcium/phosphorus content and
mineral formation of DPSCs + beta-TCP were significantly higher than DPSCs +
nHAC/LA. When implanted into the back of SCID mice, nHAC/PLA alone had no new
bone formation, newly formed mature bone and osteoid were only observed in beta
TCP alone, DPSCs + nHAC/PLA and DPSCs + beta-TCP, and this three groups displayed
increased bone formation over the 12-week period. The percentage of total bone
formation area had no difference between DPSCs + beta-TCP and DPSCs + nHAC/PLA at
each time point, but the percentage of mature bone formation area of DPSCs + beta
TCP was significantly higher than that of DPSCs + nHAC/PLA. Our results
demonstrated that the DPSCs on nHAC/PLA had a better proliferation, and that the
DPSCs on beta-TCP had a more mineralization in vitro, much more newly formed
mature bones in vivo were presented in DPSCs + beta-TCP group. These findings
have provided a further knowledge that scaffold architecture has different
influence on the attachment, proliferation and differentiation of cells. This
study may provide insight into the clinical periodontal bone tissue repair with
DPSCs + beta-TCP construct.
PMID- 25131440
TI - Bi-compartmental elderly or adult dynamic digestion models applied to interrogate
protein digestibility.
AB - The world's population is inevitably ageing thanks to modern progress; however,
the development of food and oral formulations tailored to the needs of the
elderly is still in its infancy. In vitro digestion models offer high throughput,
robust and practically ethics free evaluation of the digestive fate of ingested
products. To date, no data have been made publicly available to facilitate the
development or application of an in vitro model mirroring the physicochemical
conditions of the elderly gastrointestinal system. This study reports the
development of a novel and highly bio-relevant in vitro model based on two
serially connected bioreactors recreating the dynamic conditions of the adult or
elderly alimentary canal. This report and its supplementary material describe in
detail the set-up of the system, the applied physicochemical parameters and the
development of the controlling software. These are intended to openly depict a
versatile platform, which could assist future efforts to develop age-tailored
oral formulations. SDS-PAGE analyses of samples collected from the in vitro
digestion of beta-lactoglobulin, alpha-lactalbumin and lactoferrin suggest the
bioaccessibility of "slow digesting" and "fast digesting" proteins identified in
adult models do not necessarily maintain this trait under elderly gastro
intestinal conditions. Overall, this study brings forward a new generic yet
advanced model that could facilitate age-tailoring the digestive fate of liquid
formulations.
PMID- 25131438
TI - Lipid interactions during virus entry and infection.
AB - For entry and infection viruses have developed numerous strategies to subjugate
indispensable cellular factors and functions. Host cell lipids and cellular lipid
synthesis machinery are no exception. Not only do viruses exploit existing lipid
signalling and modifications for virus entry and trafficking, they also reprogram
lipid synthesis, metabolism, and compartmentalization for assembly and egress.
Here we review these various concepts and highlight recent progress in
understanding viral interactions with host cell lipids during entry and assembly.
PMID- 25131441
TI - The role of the hippocampus in passive and active spatial learning.
AB - Rats with lesions of the hippocampus or sham lesions were required in four
experiments to escape from a square swimming pool by finding a submerged
platform. Experiments 1 and 2 commenced with passive training in which rats were
repeatedly placed on the platform in one corner-the correct corner-of a pool with
distinctive walls. A test trial then revealed a strong preference for the correct
corner in the sham but not the hippocampal group. Subsequent active training of
being required to swim to the platform resulted in both groups acquiring a
preference for the correct corner in the two experiments. In Experiments 3 and 4,
rats were required to solve a discrimination between different panels pasted to
the walls of the pool, by swimming to the middle of a correct panel. Hippocampal
lesions prevented a discrimination being formed between panels of different
lengths (Experiment 3), but not between panels showing lines of different
orientations (Experiment 4); rats with sham lesions mastered both problems. It is
suggested that an intact hippocampus is necessary for the formation of stimulus
goal associations that permit successful passive spatial leaning. It is further
suggested that an intact hippocampus is not necessary for the formation of
stimulus-response associations, except when they involve information about length
or distance.
PMID- 25131442
TI - Short- and long-term prognosis of previous and new-onset atrial fibrillation in
ST-segment elevation acute myocardial infarction.
AB - INTRODUCTION AND OBJECTIVES: The impact of atrial fibrillation on the prognosis
of myocardial infarction is still the subject of debate. We analyzed the
influence of previous and new-onset atrial fibrillation on in-hospital and long
term prognosis in patients with acute myocardial infarction. METHODS: Prospective
study of 4284 patients with ST-segment elevation acute myocardial infarction. We
studied all-cause in-hospital and long-term mortality (median, 7.2 years) using
adjusted models. RESULTS: In total, 3.2% of patients had previous atrial
fibrillation and 9.8% had new-onset atrial fibrillation. In general, both groups
of patients had a high baseline risk profile and an increased likelihood of in
hospital complications. The crude in-hospital mortality rate was higher in
patients with previous atrial fibrillation than in those with new-onset atrial
fibrillation (22% vs 12%; P<.001; 30% vs 10%; P<.001). The long-term mortality
rate was 11.11/100 patient-years in patients with previous atrial fibrillation
and 5.35/100 patient years in those with new-onset atrial fibrillation (both
groups, P<.001). New-onset fibrillation alone (odds ratio=1.55; 95% confidence
interval, 1.08-2.22) was an independent predictor of in-hospital mortality.
Previous atrial fibrillation (hazard ratio=1.24; 95% confidence interval, 0.94
1.64) and new-onset atrial fibrillation (hazard ratio=0.98; 95% confidence
interval, 0.80-1.21) were not independent predictors of long-term mortality.
CONCLUSIONS: New-onset atrial fibrillation during hospitalization is an
independent risk factor for in-hospital mortality in acute myocardial infarction.
PMID- 25131443
TI - Ecological mechanisms underpinning climate adaptation services.
AB - Ecosystem services are typically valued for their immediate material or cultural
benefits to human wellbeing, supported by regulating and supporting services.
Under climate change, with more frequent stresses and novel shocks, 'climate
adaptation services', are defined as the benefits to people from increased social
ability to respond to change, provided by the capability of ecosystems to
moderate and adapt to climate change and variability. They broaden the ecosystem
services framework to assist decision makers in planning for an uncertain future
with new choices and options. We present a generic framework for operationalising
the adaptation services concept. Four steps guide the identification of intrinsic
ecological mechanisms that facilitate the maintenance and emergence of ecosystem
services during periods of change, and so materialise as adaptation services. We
applied this framework for four contrasted Australian ecosystems. Comparative
analyses enabled by the operational framework suggest that adaptation services
that emerge during trajectories of ecological change are supported by common
mechanisms: vegetation structural diversity, the role of keystone species or
functional groups, response diversity and landscape connectivity, which underpin
the persistence of function and the reassembly of ecological communities under
severe climate change and variability. Such understanding should guide ecosystem
management towards adaptation planning.
PMID- 25131444
TI - Abortion providers, stigma and professional quality of life.
AB - OBJECTIVES: The Providers Share Workshop (PSW) provides abortion providers safe
space to discuss their work experiences. Our objectives were to assess changes in
abortion stigma over time and explore how stigma is related to aspects of
professional quality of life, including compassion satisfaction, burnout and
compassion fatigue for providers participating in the workshops. STUDY DESIGN:
Seventy-nine providers were recruited to the PSW study. Surveys were completed
prior to, immediately following and 1 year after the workshops. The outcome
measures were the Abortion Provider Stigma Survey and the Professional Quality of
Life (ProQOL) survey. Baseline ProQOL scores were compared to published averages
using t tests. Changes in abortion stigma and aspects of professional quality of
life were assessed by fitting a two-level random-effects model with repeated
measures at level 1 (period-level) and static measures (e.g., demographic data)
at level 2 (person-level). Potential covariates included age, parenting status,
education, organizational tenure, job type and clinic type (stand-alone vs.
hospital-based clinics). RESULTS: Compared to other healthcare workers, abortion
providers reported higher compassion satisfaction (t=2.65, p=.009) and lower
burnout (t=5.13, p<.0001). Repeated-measures analysis revealed statistically
significant decreases in stigma over time. Regression analysis identified
abortion stigma as a significant predictor of lower compassion satisfaction,
higher burnout and higher compassion fatigue. CONCLUSIONS: Participants in PSW
reported a reduction in abortion stigma over time. Further, stigma is an
important predictor of compassion satisfaction, burnout and compassion fatigue,
suggesting that interventions aimed at supporting the abortion providing
workforce should likely assess abortion stigma. IMPLICATIONS: Stigma is an
important predictor of compassion satisfaction, burnout and compassion fatigue
among abortion care providers. Therefore, strengthening human resources for
abortion care requires stigma reduction efforts. Participants in the PSWs show
reductions in stigma over time.
PMID- 25131445
TI - APRI and FIB-4 are good predictors of the stage of liver fibrosis in chronic
hepatitis B: the Chronic Hepatitis Cohort Study (CHeCS).
AB - We aim to determine the predictive ability of APRI, FIB-4 and AST/ALT ratio for
staging of liver fibrosis and to differentiate significant fibrosis (F2-F4) from
none to minimal fibrosis (F0-F1) in chronic hepatitis B (CHB). Liver biopsy
results were mapped to an F0-4 equivalent fibrosis stage. Mean APRI and FIB-4
scores were significantly higher for each successive fibrosis level from F1 to F4
(P < 0.05). Based on optimized cut-offs, the AUROCs in distinguishing F2-F4 from
F0 to F1 were 0.81 (0.76-0.87) for APRI, 0.81 (0.75-0.86) for FIB-4 and 0.56
(0.49-0.64) for AST/ALT ratio. APRI and FIB-4 distinguished F2-F4 from F0 to F1
with good sensitivity and specificity and can be useful for treatment decisions
and monitoring progression of fibrosis.
PMID- 25131447
TI - Interplay between brain stem angiotensins and monocyte chemoattractant protein-1
as a novel mechanism for pressor response after ischemic stroke.
AB - Pressor response after stroke commonly leads to early death or susceptibility to
stroke recurrence, and detailed mechanisms are still lacking. We assessed the
hypothesis that the renin-angiotensin system contributes to pressor response
after stroke by differential modulation of the pro-inflammatory chemokine
monocyte chemoattractant protein-1 (MCP-1) in the rostral ventrolateral medulla
(RVLM), a key brain stem site that maintains blood pressure. We also investigated
the beneficial effects of a novel renin inhibitor, aliskiren, against stroke
elicited pressor response. Experiments were performed in male adult Sprague
Dawley rats. Stroke induced by middle cerebral artery occlusion elicited
significant pressor response, accompanied by activation of angiotensin II (Ang
II)/type I receptor (AT1R) and AT2R signaling, depression of Ang-(1-7)/MasR and
Ang IV/AT4R cascade, alongside augmentation of MCP-1/C-C chemokine receptor 2
(CCR2) signaling and neuroinflammation in the RVLM. Stroke-elicited pressor
response was significantly blunted by antagonism of AT1R, AT2R or MCP-1/CCR2
signaling, and eliminated by applying Ang-(1-7) or Ang IV into the RVLM.
Furthermore, stroke-activated MCP-1/CCR2 signaling was enhanced by AT1R and AT2R
activation, and depressed by Ang-(1-7)/MasR and Ang IV/AT4R cascade. Aliskiren
inhibited stroke-elicited pressor response via downregulating MCP-1/CCR2 activity
and reduced neuroinflammation in the RVLM; these effects were potentiated by Ang
(1-7) or Ang IV. We conclude that whereas Ang II/AT1R or Ang II/AT2R signaling in
the brain stem enhances, Ang-(1-7)/MasR or Ang IV/AT4R antagonizes pressor
response after stroke by differential modulations of MCP-1 in the RVLM.
Furthermore, combined administration of aliskiren and Ang-(1-7) or Ang IV into
the brain stem provides more effective amelioration of stroked-induced pressor
response.
PMID- 25131446
TI - Deep brain stimulation in rats: different targets induce similar antidepressant
like effects but influence different circuits.
AB - Recent studies in patients with treatment-resistant depression have shown similar
results with the use of deep brain stimulation (DBS) in the subcallosal cingulate
gyrus (SCG), ventral capsule/ventral striatum (VC/VS) and nucleus accumbens
(Acb). As these brain regions are interconnected, one hypothesis is that by
stimulating these targets one would just be influencing different relays in the
same circuitry. We investigate behavioral, immediate early gene expression, and
functional connectivity changes in rats given DBS in homologous regions, namely
the ventromedial prefrontal cortex (vmPFC), white matter fibers of the frontal
region (WMF) and nucleus accumbens. We found that DBS delivered to the vmPFC, Acb
but not WMF induced significant antidepressant-like effects in the FST (31%, 44%,
and 17% reduction in immobility compared to controls). Despite these findings,
stimulation applied to these three targets induced distinct patterns of regional
activity and functional connectivity. While animals given vmPFC DBS had increased
cortical zif268 expression, changes after Acb stimulation were primarily observed
in subcortical structures. In animals receiving WMF DBS, both cortical and
subcortical structures at a distance from the target were influenced by
stimulation. In regard to functional connectivity, DBS in all targets decreased
intercorrelations among cortical areas. This is in contrast to the clear
differences observed in subcortical connectivity, which was reduced after vmPFC
DBS but increased in rats receiving Acb or WMF stimulation. In conclusion,
results from our study suggest that, despite similar antidepressant-like effects,
stimulation of the vmPFC, WMF and Acb induces distinct changes in regional brain
activity and functional connectivity.
PMID- 25131448
TI - Folate deficiency-induced oxidative stress contributes to neuropathy in young and
aged zebrafish--implication in neural tube defects and Alzheimer's diseases.
AB - Folate is a nutrient essential for the development, function and regeneration of
nervous systems. Folate deficiency has been linked to many neurological disorders
including neural tube defects in fetus and Alzheimer's diseases in the elderly.
However, the etiology underlying these folate deficiency-associated diseases is
not completely understood. In this study, zebrafish transgenic lines with timing
and duration-controllable folate deficiency were developed by ectopically
overexpressing a recombinant EGFP-gamma-glutamyl hydrolase (gammaGH). Impeded
neural crest cell migration was observed in the transgenic embryos when folate
deficiency was induced in early stages, leading to defective neural tube closure
and hematopoiesis. Adding reduced folate or N-acetylcysteine reversed the
phenotypic anomalies, supporting the causal link between the increased oxidative
stress and the folate deficiency-induced abnormalities. When folate deficiency
was induced in aged fish accumulation of beta-amyloid and phosphorylated Tau
protein were found in the fish brain cryo-sections. Increased autophagy and
accumulation of acidic autolysosome were apparent in folate deficient
neuroblastoma cells, which were reversed by reduced folate or N-acetylcysteine
supplementation. Decreased expression of cathepsin B, a lysosomal protease, was
also observed in cells and tissue with folate deficiency. We concluded that
folate deficiency-induced oxidative stress contributed to the folate deficiency
associated neuropathogenesis in both early and late stages of life.
PMID- 25131450
TI - Use of Sato's curved laryngoscope and an insulated-tip knife for endoscopic
incisional therapy of esophageal web.
AB - We experienced two cases of esophageal web accompanying severe stricture that
were treated by endoscopic incisions with an insulated-tip knife (IT-knife). With
attention paid to the mucosa at the stricture, the lesion was incised with an IT
knife without complications. Sato's curved laryngoscope was used even in cervical
esophageal lesions and an excellent field was secured.
PMID- 25131451
TI - Relationship of hyperinsulinaemia, insulin resistance and beta-cell dysfunction
with incident diabetes and pre-diabetes: the Tehran Lipid and Glucose Study.
AB - AIMS: To examine the association of fasting insulin, insulin resistance and
reduced beta-cell function with incident Type 2 diabetes and pre-diabetes
(isolated impaired fasting glucose/isolated impaired glucose tolerance and
combined impaired fasting glucose/impaired glucose tolerance). METHODS: An
Iranian population comprising 1532 men and 2221 women, aged >= 20 years, with
normal fasting glucose and normal glucose tolerance at baseline, were enrolled in
the study. Multivariable Cox proportional hazard models were used to calculate
the hazard ratios and 95% CIs of fasting insulin, updated homeostasis model
assessments of insulin resistance and beta-cell function for incident Type 2
diabetes, isolated impaired fasting glucose, isolated impaired glucose tolerance
and combined impaired fasting glucose/impaired glucose tolerance. RESULTS: During
a median follow-up of 9.2 years, the annual incidence rates (95% CI) of diabetes
were 3.73 (2.74-4.94) and 4.06 (3.21-5.06) per 1000 person-years in men and
women, respectively. In both men and women, fasting insulin and homeostasis model
assessment of insulin resistance (>= 75th percentile) were significantly
associated with incident diabetes and combined impaired fasting glucose/impaired
glucose tolerance; however, reduced beta-cell function as measured by homeostasis
model assessment of beta-cell function (< 25th percentile) was associated with
incident isolated impaired fasting glucose solely in men [hazard ratio 1.35 (95%
CI 1.02-1.78)] in multivariable analysis including waist-hip ratio).
Hyperinsulinaemia, insulin resistance and beta-cell dysfunction were not related
to the incidence of isolated impaired glucose tolerance in either gender.
CONCLUSIONS: Fasting hyperinsulinaemia and insulin resistance were strong risk
factors for progression to diabetes and combined impaired fasting
glucose/impaired glucose tolerance in a population with normal fasting
glucose/normal glucose tolerance. In addition, impaired beta-cell function at
baseline was related to the development of isolated impaired fasting glucose only
in men and, in both men and women, neither insulin resistance nor beta-cell
dysfunction were associated with incident isolated impaired glucose tolerance.
PMID- 25131452
TI - Genetic history of hepatitis C virus in Pakistan.
AB - Hepatitis C virus (HCV) genotype 3a accounts for ~80% of HCV infections in
Pakistan, where ~10 million people are HCV-infected. Here, we report analysis of
the genetic heterogeneity of HCV NS3 and NS5b subgenomic regions from genotype 3a
variants obtained from Pakistan. Phylogenetic analyses showed that Pakistani
genotype 3a variants were as genetically diverse as global variants, with
extensive intermixing. Bayesian estimates showed that the most recent ancestor
for genotype 3a in Pakistan was last extant in ~1896-1914 C.E. (range: 1851
1932). This genotype experienced a population expansion starting from ~1905 to
~1970 after which the effective population leveled. Death/birth models suggest
that HCV 3a has reached saturating diversity with decreasing turnover rate and
positive extinction. Taken together, these observations are consistent with a
long and complex history of HCV 3a infection in Pakistan.
PMID- 25131453
TI - Effects of three different low-intensity exercise interventions on physical
performance, muscle CSA and activities of daily living: a randomized controlled
trial.
AB - OBJECTIVES: To evaluate the short-term effects of three different resistance
training programs, conducted at low intensity, on physical performance, muscle
cross-sectional area (CSA) and the capacity to perform daily tasks in older
adults living in a geriatric nursing home. DESIGN: Randomized controlled trial,
with a 4-month intervention period. SETTING: A geriatric nursing home in
Valencia, Spain. PARTICIPANTS: Eighty-nine adults aged 75 to 96 who were
independent in their daily activities. INTERVENTION: After a baseline assessment,
the participants were randomly assigned to the control group or one of the three
intervention groups: volitional contraction (VC; n=22), neuromuscular electrical
stimulation (NMES; n=22), or neuromuscular electrical stimulation superimposed
onto voluntary contractions (NMES+; n=22). The intervention focused on knee
extension exercises and its intensity was set at 40% of one-repetition maximum
(1RM). MEASUREMENTS: The primary outcome measure was mobility. Secondary outcomes
were rectus femoris CSA, balance, aerobic endurance, upper-body strength and the
capacity to perform daily tasks. All data were collected at baseline and after
the 4-month intervention period. RESULTS: The two-way ANOVA analysis showed a
significant group*time interaction effect for the mobility (P=.022), rectus
femoris CSA (P=.001), and the capacity to perform daily tasks (P=.05). The within
group analysis found a more prominent effect in the NMES+ group. Significant
improvements were seen in rectus femoris CSA and the capacity to perform daily
tasks in all intervention groups. Mobility only improved in the NMES+ group
(P=.026). CONCLUSION: From a short-term perspective, NMES+ exercise training,
performed at low intensity, can improve physical performance, muscle CSA, and the
capacity to perform daily activities, and to partially mitigate age-related
consequences in older adults.
PMID- 25131454
TI - Testicular hypofunction and multiple sclerosis risk: a record-linkage study.
AB - The influence of gonadal hormones on multiple sclerosis (MS) is not well
characterized and has thus far been investigated primarily in animal models or as
a proposed therapeutic approach. We investigated a potential association between
testicular hypofunction, as a proxy for low testosterone levels, and MS risk
through analysis of linked English national Hospital Episode Statistics from 1999
to 2011. We report a strong positive association between testicular hypofunction
and subsequent MS (rate ratio = 4.62, 95% confidence interval = 2.3-8.24, p <
0.0001). Future work should aim more directly to elucidate the relationship
between testosterone levels and MS in both males and females.
PMID- 25131456
TI - A facilely synthesized amino-functionalized metal-organic framework for highly
specific and efficient enrichment of glycopeptides.
AB - A facilely synthesized amino-functionalized metal-organic framework (MOF) MIL
101(Cr)-NH2 was first applied for highly specific glycopeptide enrichment based
on the hydrophilic interactions. With the special characteristics of the MOF, the
material performed well in selectivity and sensitivity for both standard
glycoprotein samples and complex biological samples.
PMID- 25131449
TI - HDL and cognition in neurodegenerative disorders.
AB - High-density lipoproteins (HDLs) are a heterogeneous group of lipoproteins
composed of various lipids and proteins. HDL is formed both in the systemic
circulation and in the brain. In addition to being a crucial player in the
reverse cholesterol transport pathway, HDL possesses a wide range of other
functions including anti-oxidation, anti-inflammation, pro-endothelial function,
anti-thrombosis, and modulation of immune function. It has been firmly
established that high plasma levels of HDL protect against cardiovascular
disease. Accumulating evidence indicates that the beneficial role of HDL extends
to many other systems including the central nervous system. Cognition is a
complex brain function that includes all aspects of perception, thought, and
memory. Cognitive function often declines during aging and this decline manifests
as cognitive impairment/dementia in age-related and progressive neurodegenerative
disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease,
and amyotrophic lateral sclerosis. A growing concern is that no effective therapy
is currently available to prevent or treat these devastating diseases. Emerging
evidence suggests that HDL may play a pivotal role in preserving cognitive
function under normal and pathological conditions. This review attempts to
summarize recent genetic, clinical and experimental evidence for the impact of
HDL on cognition in aging and in neurodegenerative disorders as well as the
potential of HDL-enhancing approaches to improve cognitive function.
PMID- 25131457
TI - Self-aggregation of synthetic zinc chlorophyll derivatives possessing 3(1)
hydroxy or methoxy group and 13(1)-mono- or dicyanomethylene moiety in nonpolar
organic solvents as models of chlorosomal bacteriochlorophyll-d aggregates.
AB - Methyl 13(1)-(di)cyanomethylene-pyropheophorbides were synthesized by Knoevenagel
reactions of the corresponding 13(1)-oxo-chlorins prepared from modifying
chlorophyll-a with malononitrile or cyanoacetic acid. Alternatively, methyl 13(1)
cyanomethylene-pyropheophorbides were produced by Wittig reactions of 13(1)-oxo
chlorins with Ph3P=CHCN. Self-aggregation of zinc complexes of the semi-synthetic
chlorophyll derivatives possessing a hydroxy or methoxy group at the 3(1)
position was examined in 1%(v/v) tetrahydrofuran or dichloromethane and hexane by
electronic absorption and circular dichroism spectroscopy. Although
intermolecular hydrogen-bonding between the 3(1)-hydroxy and 13(1)-oxo groups of
bacteriochlorophylls-c/d/e/f was essential for their self-aggregation in natural
light-harvesting antenna systems (=chlorosomes), zinc 3(1)-hydroxy-13(1)
di/monocyanomethylene-chlorins self-aggregated in the less/lesser polar organic
solvents to form chlorosome-like large oligomers in spite of lacking the 13(1)
oxo moiety as the hydrogen-bonding acceptor. Zinc 3(1)-methoxy-13(1)
dicyanomethylene-chlorin gave similar self-aggregates regardless of lack of both
the 3(1)-hydroxy and 13(1)-oxo groups. The present self-aggregation was
ascribable to stronger coordination of the 3(1)-oxygen atom to the central zinc
than the conventional systems, where the electron-withdrawing cyano group(s)
increased the coordinative ability of the central zinc through the chlorin pi
system.
PMID- 25131459
TI - [Transperitoneal laparoscopic ureteral reimplantation with extracorporeal
tailoring and direct nipple ureteroneocystostomy for adult obstructive
megaureter].
AB - This paper focuses on a novel modified technique about the treatment of adult
obstructed megaureter by the transperitoneal laparoscopic procedure. With the
improvement of the laparoscopic surgery, many urological surgeries can be safely
and effectually performed by laparoscopic approach. The previously reported
laparoscopic methods for treatment of adult obstructed megaureter were complex
and time-consuming. To simplify the method, we modified the laparoscopic approach
based on the previous methods. The innovative points of our novel technique are
the extracorporeal tailoring of ureter and nipple ureteroneocystostomy. By this
modified procedure, the time of operation can be obviously reduced while the
procedure is effective. We hope this modified procedure will be accepted by more
urologists.
PMID- 25131460
TI - [Incidence and clinicopathological characteristics of incidental prostatic
adenocarcinoma in radical cystoprostatectomy specimens].
AB - OBJECTIVE: To analyze the incidence and clinicopathological features of
incidental prostate cancer (IPCa) in specimens from radical cystoprostatectomy
(RCP) for bladder cancer. METHODS: We retrospectively reviewed the
histopathological features of 865 male patients who underwent an RCP between
January 2005 and March 2014. No patients had preoperative clinical or biological
suspicion of prostate cancer (PCa). RESULTS: Among the 865 specimens, IPCa was
diagnosed in 235 patients (27.2%). Most tumors (228/235, 97.0%) were organ
confined (pT2); And 7 cases (3.0 %) of them were diagnosed at T3. Gleason score
was < 6 in 84 cases (35.7 %), 6 in 77 cases (32.8%), 7 in 64 cases (27.2 %), and
> 7 in 10 cases (4.3 %). CONCLUSION: The rate of incidentally diagnosed IPCa was
8.5%, and that in RCP and TURP specimens was 19.5% and 4.4% respectively. The
majority of these IPCas were organ-confined. Gleason score in most of these
specimens was <= 7. Moreover, prostate examination in the RCP specimen should be
careful and sufficient, whole-amount prostate sections improve diagnostic
accuracy.
PMID- 25131455
TI - Endothelin@25 - new agonists, antagonists, inhibitors and emerging research
frontiers: IUPHAR Review 12.
AB - Since the discovery of endothelin (ET)-1 in 1988, the main components of the
signalling pathway have become established, comprising three structurally similar
endogenous 21-amino acid peptides, ET-1, ET-2 and ET-3, that activate two GPCRs,
ETA and ETB . Our aim in this review is to highlight the recent progress in ET
research. The ET-like domain peptide, corresponding to prepro-ET-193-166 , has
been proposed to be co-synthesized and released with ET-1, to modulate the
actions of the peptide. ET-1 remains the most potent vasoconstrictor in the human
cardiovascular system with a particularly long-lasting action. To date, the major
therapeutic strategy to block the unwanted actions of ET in disease, principally
in pulmonary arterial hypertension, has been to use antagonists that are
selective for the ETA receptor (ambrisentan) or that block both receptor subtypes
(bosentan). Macitentan represents the next generation of antagonists, being more
potent than bosentan, with longer receptor occupancy and it is converted to an
active metabolite; properties contributing to greater pharmacodynamic and
pharmacokinetic efficacy. A second strategy is now being more widely tested in
clinical trials and uses combined inhibitors of ET-converting enzyme and neutral
endopeptidase such as SLV306 (daglutril). A third strategy based on activating
the ETB receptor, has led to the renaissance of the modified peptide agonist
IRL1620 as a clinical candidate in delivering anti-tumour drugs and as a
pharmacological tool to investigate experimental pathophysiological conditions.
Finally, we discuss biased signalling, epigenetic regulation and targeting with
monoclonal antibodies as prospective new areas for ET research.
PMID- 25131461
TI - [Expression of brainderived neurotrophic factor in urine of patients with benign
prostatic hyperplasia complicated overactive bladder symptoms].
AB - OBJECTIVE: To investigate the expression of urinary brainderived neurotrophic
factor (BDNF) in benign prostatic hyperplasia patients with overactive bladder
(OAB) symptoms and its correlation with the severity of OAB symptoms. METHODS:
According to the inclusion and exclusion criteria, a total of 178 patients with
benign prostatic hyperplasia who were to undergo transurethral resection of
prostate (TURP) were enrolled in this study. All the patients had accepted basic
preoperative evaluations, as well as an assessment of their International
Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS). The
patients who had been scheduled for surgery had to take the urodynamic
assessment. Urinary BDNF levels were measured by the enzyme-linked immunosorbent
assay (ELISA) and the results were further normalized to the concentration of
urinary creatinine (BDNF/Cr, mg/mol). RESULTS: The urinary BDNF/Cr levels of the
patients with moderate and severe lower urinary tract symptoms were (1.189 +/-
0.753) mg/mol and (1.817 +/- 1.110) mg/mol (P < 0.001). The urinary BDNF/Cr
levels of the patients with grades III-VI obstruction were (1.382 +/- 0.945)
mg/mol, (1.435 +/- 0.938) mg/mol, (1.640 +/- 1.104) mg/mol, and (1.653 +/- 1.019)
mg/mol, respectively (P > 0.05). There was no correlation between the urinary
BDNF/Cr levels and the severity of obstruction (r = 0.103, P = 0.173). The
urinary BDNF/Cr levels in the patients with and without OAB symptoms were (1.913
+/- 0.843) mg/mol and (0.297 +/- 0.183) mg/mol (P < 0.001). The urinary BDNF/Cr
levels in the patients with mild, moderate and severe OAB symptoms were (1.501 +/
0.543) mg/mol, (1.806 +/- 0.703) mg/mol and (2.560 +/- 0.979) mg/mol,
respectively (P < 0.05). There was a correlation between the urinary BDNF/Cr
levels and the severity of OAB symptoms (r = 0.743, P < 0.001). The urinary
BDNF/Cr levels in the patients with urodynamic detrusor overativity were
significantly higher than those without detrusor overativity [(1.917 +/- 0.866)
mg/mol and (1.194 +/- 1.013) mg/mol, P < 0.001]. CONCLUSION: There is no
correlation between urinary BDNF and severity of obstruction in benign prostatic
hyperplasia patients with moderate and severe lower urinary tract symptoms. The
urinary BDNF levels in patients with OAB symptoms are elevated compared with
patients without OAB symptoms, and are correlated with the severity of OAB
symptoms.
PMID- 25131462
TI - [Characteristics of lymph node metastasis in patients undergoing radical
cystectomy for bladder cancer: a retrospective single-center study of 522 cases].
AB - OBJECTIVE: To investigate the characteristics and related influence factors of
lymph node metastases in patients undergoing radical cystectomy and lymph node
dissection for bladder cancer. METHODS: The data of 522 patients who underwent
radical cystectomy and pelvic lymph node dissection at Department of Urology,
Peking University First Hospital from 1998 to 2012, were retrospectively
collected, and the lymph node mapping was performed in all the patients to
determine the location of metastatic lymph nodes. RESULTS: For the 522 patients
with bladder cancer, lymph node metastasis occurred in 99 patients, and the
incidence of lymph node metastasis was 19.0%. The incidence at different tumor
stages was: 3.7% in T1 (6/164), 10.5% in T2 (17/160), 36.7% in T3(40/107), and
41.9% in T4 (36/86). The most common involved lymph nodes were
hypogastric/obturator lymph nodes (77/99, 77.8%) and external iliac lymph nodes
(35/99, 35.4%). The mean number of lymph nodes dissected was 11.6 (1-51). The
lymph node density (number of lymph nodes involved/number of lymph nodes removed)
was 44.1%. The incidence of lymph node metastasis was statistical related to
tumor stage (P < 0.01, OR 2.71,95% CI 2.13-3.44) and tumor grade (P < 0.01, OR
3.81,95% CI 1.66-8.74), while age, gender, smoke history, and weight had no
statistical significance. CONCLUSION: Lymph node metastasis is the most common
metastasis route of bladder cancer. The incidence of lymph node tumor involvement
is correlated with increasing tumor stage and tumor grade. The most common
involved lymph nodes are hypogastric/obturator lymph nodes and external iliac
lymph nodes. Radical cystectomy and bilateral pelvic lymph nodes dissection are
of great significance in the treatment of bladder cancer.
PMID- 25131463
TI - [Long-term outcome of isolated local recurrence following radical nephrectomy].
AB - OBJECTIVE: To characterize the long-term outcome of surgical extirpation for
local recurrence after radical nephrectomy of renal cell carcinoma (RCC) and
identify prognostic factors for locally recurrent RCC. METHODS: Peking University
First Hospital urologic database was queried for all patients with isolated local
recurrence following radical nephrectomy for localized RCC. According to previous
literature, local recurrence included relapse in the renal fossa, ipsilateral
adrenal gland and ipsilateral retroperitoneal lymph nodes. The median follow up
was 62 months. The cancer specific survival and relapse patterns were estimated
using the Kaplan-Meier method. RESULTS: In our institutional database,1 045
patients were treated with nephrectomy for localized RCC from January 1994 to
December 2011.With a postoperative follow-up of (62.7 +/- 36.2) months, 15
patients (1.44%) experienced local recurrence, 9 of which were managed by
surgical resection, and the rest 6 did not receive operation. The patients who
received surgical resection had a 1-year cancer specific survival rate of 87%,
compared with 60% of the patients without receiving surgical treatment. The 4
year cancer specific survival rate was 72% vs. 30%.The survival time was(51.8 +/-
7.4) months vs. (28.4 +/- 9.2) months. The recurrence interval was (39.4 +/-
29.5) months vs. (29.3 +/- 23.9) months. CONCLUSION: Surgical resection for local
recurrence of RCC in selected patients is a feasible management and may prolong
the survival time.
PMID- 25131458
TI - Endogenous versus exogenous markers of adult neurogenesis in canaries and other
birds: advantages and disadvantages.
AB - Although the existence of newborn neurons had originally been suggested, but not
broadly accepted, based on studies in adult rodent brains, the presence of an
active neurogenesis process in adult homoeothermic vertebrates was first firmly
established in songbirds. Adult neurogenesis was initially studied with the
tritiated thymidine technique, later replaced by the injection and detection of
the marker of DNA replication 5-bromo-2'-deoxyuridine (BrdU). More recently,
various endogenous markers were used to identify young neurons or cycling
neuronal progenitors. We review here the respective advantages and pitfalls of
these different approaches in birds, with specific reference to the microtubule
associated protein, doublecortin (DCX), that has been extensively used to
identify young newly born neurons in adult brains. All these techniques of course
have limitations. Exogenous markers label cells replicating their DNA only during
a brief period and it is difficult to select injection doses that would
exhaustively label all these cells without inducing DNA damage that will also
result in some form of labeling during repair. On the other hand, specificity of
endogenous markers is difficult to establish due to problems related to the
specificity of antibodies (these problems can be, but are not always, addressed)
and more importantly because it is difficult, if not impossible, to prove that a
given marker exhaustively and specifically labels a given cell population.
Despite these potential limitations, these endogenous markers and DCX staining in
particular clearly represent a useful approach to the detailed study of
neurogenesis especially when combined with other techniques such as BrdU.
PMID- 25131464
TI - [Effects of interval time between prostate biopsy and surgery on laparoscopic
radical prostatectomy].
AB - OBJECTIVE: To investigate the length of interval time between biopsy and
laparascopic radical prostatectomy in difficulty and effects of surgery. METHODS:
We retrospectively analyzed 89 cases of laparascopic radical prostatectomy from
June 2011 to September 2013. The patients were divided into two groups according
to the interval time of 6 weeks. The mean interval time was 3.1 weeks (ranging
from 1.5 to 4.4 weeks) in group IT< 6 weeks and 4.4 weeks (ranging from 6.0 to
16.2 weeks) in group IT >= 6 weeks. The mean age was 67 years (ranging from 57 to
78 years). The PSA level was 15.4 MUg/L (ranging from 5.2 to 72.0). The prostate
volume was 55 mL (ranging from 42 to 89 mL). The parameters, such as operation
duration, blood loss, positive surgical margin rate, incharge time postoperation,
were evaluated. RESULTS: All the surgeries went successfully. The average
operation duration was 150 min (ranging from 110 to 242 min), and the blood loss
was 230 mL (ranging from 100 to 750 mL). The positive surgical margin rate was
18% and the urinary continence rate was 100% at 3 months after operation. The
clinical recurrence was not found during the follow-up. No significant difference
was found between the groups in the patients' age, preoperative PSA, Gleason
score and prostate volume (P > 0.05). No statistical significance existed in the
operation time, blood loss, positive margin rate, post-operative hospital stay,
urinary continence rate at 3 months after operation, postoperative differences of
clinical recurrence rates. CONCLUSION: The length of interval time between
prostate biopsy and laparascopic radical prostatectomy does not influence the
difficulty and effect in the early stage, and the long time survival and
recurrent rate need further observation.
PMID- 25131465
TI - [Technique of renal pedicle control in transperitoneal laparoscopic nephrectomy:
experience of 191 cases by a single surgeon].
AB - OBJECTIVE: To explore the technique of vascular control in transperitoneal
laparoscopic nephrectomy. METHODS: From May 2010 to September 2013, 191
consecutive transperitoneal laparoscopic nephrectomies were performed by a single
surgeon. The operations included 116 radical nephrectomies, 57
nephroureterectomies, and 18 simple nephrectomies. Improved 4-trocar method was
applied. Through lifting up inferior pole of the kidney by an assistant, and
observing renal vascular from the bottom or back of the kidney, the exposure of
renal vessels were improved. The renal vessels were managed with Hem-o-lock or
Endo GIA. For tumors of stage >= T2, ipsilateral lymph node dissection of renal
hilus was performed. RESULTS: Of the entire 191 cases,190 were performed
successfully, only 1 converted to open surgery because of the difficulty in
separating the tumor from the invaded colon. The average time of operation was
171.5 min (74-352). The blood loss was 5-1 000 mL with an average of 94.8 mL. The
complications included vascular injuries (5 cases), cerebral infarction
accompanied by acute renal injury (1 case), and pulmonary infection (2 cases).
The mean postoperative hospital stay was 5.6 days (2-19 days). No perioperative
death occurred. CONCLUSION: The reformative technique of vascular control could
improve the exposure of renal vessels, increase surgery safety, and shorten the
time of transperitoneal laparoscopic nephrectomy.
PMID- 25131466
TI - [Comparison of the outcomes of microscopic varicocelectomy and laparoscopic
varicocelectomy].
AB - OBJECTIVE: To compare and analyze semen quality improvement between the patients
with microscopic varicocelectomy and laparoscopic varicocelectomy. METHODS: A
total of 291 patients with varicocele were included in this study, of whom 176
underwent microscopic varicocelectomy and 115 laparoscopic varicocelectomy. The
improvement rates of semen quality and pregnancy rates between the two groups
were compared. RESULTS: The improvement rate of sperm density in microscopic
group was significantly higher than that of laparoscopic group (87.6% vs. 73.7%,
P = 0.006). Spouse pregnancy rate of microscopic group was significantly higher
than that of laparoscopic group (45.4% vs. 30.3%, P = 0.017). CONCLUSION: The
effect of microscopic varicocelectomy was superior to that of laparoscopic
varicocelectomy.
PMID- 25131467
TI - [Analysis for related factors of upper urinary tract deterioration in patients
with spinal cord injury].
AB - OBJECTIVE: To evaluate the related factors of upper urinary tract deterioration
in spinal cord injured patients. METHODS: Medical records of spinal cord injured
patients from Jan.2002 to Sep.2009 were retrospectively reviewed. All the
patients were divided into the upper urinary tract deterioration group and non
deterioration group according to the diagnostic criteria. Indexes such as
demographic characteristic (gender, age), spinal cord injury information (cause,
level, completeness), statuses of urinary tract system (bladder management, urine
routine, urine culture, ultrasound, serum creatinine, fever caused by urinary
tract infection) and urodynamics information(bladder compliance, bladder
stability, bladder sensation, detrusor sphincter dyssynergia, detrusor leak point
pressure, maximum cystometric capacity, relative safe bladder capacity, maximum
flow rate, maximum urethra closure pressure) were compared between the two
groups.Then Logistic regression analysis were performed. RESULTS: There was
significantly difference between the two groups in spinal cord injury
level(chi(2) = 8.840, P = 0.031),bladder management(chi(2) = 11.362, P = 0.045),
urinary rutine(chi(2) = 17.983, P = 0.000), fever caused by urinary tract
infection(chi(2)= 64.472, P = 0.000), bladder compliance(chi(2) = 6.531, P =
0.011), bladder sensation(chi(2) = 11.505, P = 0.009), maximum cystometric
capacity(t = 2.209, P = 0.043), and detrusor-sphincter dyssynergia(chi(2) =
4.247, P = 0.039). The multiple-factor non-conditional Logistic regression
analysis showed that bladder management (OR = 1.114, P = 0.006), fever caused by
urinary tract infection(OR = 1.018,P = 0.000), bladder compliance (OR = 1.588, P
= 0.040) and detrusor-sphincter dyssynergia(OR = 1.023, P = 0.034) were the key
factors of upper urinary tract deterioration in spinal cord injured patients.
CONCLUSION: Urinary tract infection, lower bladder compliance, detrusor-sphincter
dyssynergia and unreasonable bladder management are the risk factors of upper
urinary tract deterioration in spinal cord injured patients.
PMID- 25131468
TI - [Ureteral stricture following renal transplantation: risk factors and surgical
management].
AB - OBJECTIVE: To evaluate the prevalence and the risk factors of the ureteral
stricture following renal transplantation and outcomes of surgical managements.
METHODS: By a retrospective analysis, we assessed 1 293 patients who underwent
renal transplantation between January 2001 and December 2013 at our center. The
patients with ureteral stricture had undergone surgical management which included
neoureterocystostomy, ureteral anastomosis with the native ureter and endoscopic
therapy. RESULTS: Ureteral stricture following renal transplantation was
diagnosed in 17 cases (1.3%) including 6 males and 11 females. The mean age of
the patients at the time of surgery was 44 (29 to 64) years. The median interval
between ureteral stricture obstruction and kidney transplantation was 4 (1 to
120) months. The ureteral stricture was significantly correlated with multiple
renal arteries, donor age and delayed graft function. The effective rate of
surgical management was 65.75%. CONCLUSION: The incidence of ureteral stricture
as a urologic complication after renal transplantation is low. The advanced
techniques that preserve the ureteric blood supply should be applied. The
surgical managements have respective advantages and disadvantages. The
neoureterocystostomy shows best outcome, while ureteral anastomosis with the
native ureter has poor outcome.
PMID- 25131469
TI - [Pathogenesis and therapy of hydronephrosis after hematopoietic stem cell
transplantation].
AB - OBJECTIVE: To investigate the pathogenesis and therapy of hydronephrosis after
hematopoietic stem cell transplantation (HSCT). METHODS: From March 2004 to March
2014, 23 patients with hydronephrosis after HSCT were identified. With these
data, the pathogenesis of hydronephrosis after HSCT were analyzed. According to
the surgical intervention of hydronephrosis and ureteral dialation of ureteral
stricture, the patients were divided into two groups, rank-sum test and exact
probability test were used to evaluate whether there were significant differences
in the time of hemorrhagic cystitis (HC) occurred, ureteritis and viremia.
RESULTS: HC, ureteritis, ureteral stenosis were all the causes of hydronephrosis
after HSCT. In this study, 69.6% (16/23) of the patients suffered from HSCT were
cured by conservative treatment, 30.4% (7/23) by surgical intervention, and 13.0%
(3/23) by insertion DJ stent or nephrostomy.Of the patients [17.4% (4/23)] who
suffered ureteral stenosis, 2 were cured after the balloon dialation of ureter, 1
needed DJ tube long-term insertion, and 1 was still followed-up. rank-sum test
and exact probability test results showed that the patients who needed surgical
intervention might suffer from HC later than other patients, and their incidences
of viremia and ureteritis were higher, but the differences between the two groups
were not statistically significant (P = 0.524, P = 0.169, and P = 0.124,
respectively). The results also showed that the ureteritis incidences of the
patients who suffered from ureteral stricture and needed ureteral dialation were
higher than that of the other patients, and the difference between the two groups
was statistically significant (P = 0.024). The patients who needed ureteral
dialation suffered from HC later and their incidences of viremia was higher, but
the differences between the two groups were not statistically significant (P =
0.73 and P = 0.27). CONCLUSION: HC, ureteritis and ureteral stenosis may cause
hydronephrosis after HSCT. Patients may treated by conservative treatment first.
Patients who suffered from HC later, viremia and especially ureteritis should be
paid more attention to, and be treated with surgical intervention when necessary.
The patients with ureteral stenosis could be treated by ureteral balloon
dialation.
PMID- 25131470
TI - [Diagnosis and treatment of hydrocephalus-accompanied renal calculi complicated
with renal tumor: 5 case reports].
AB - OBJECTIVE: To investigate the diagnosis and treatment of renal pelvic tumor
combined with renal urinary calculi and hydronephrosis. METHODS: Five patients
with renal pelvic tumor who underwent relief of the upper urinary obstruction
were reviewed. RESULTS: One of the cases lost the opportunity of surgical therapy
when pelvic tumor was detected at the advanced stage, and the other 4 cases had
received surgery and were followed up. CONCLUSION: As pelvic tumor progresses
rapidly after the renal blood flow is improved, and renal urinary calculi with
hydronephrosis relieved; the patients with renal pelvic tumor need early
diagnosis, aggressive treatment and close follow-up.
PMID- 25131471
TI - [Percutaneous renal puncture guide by a novel real-time needle-tracking
ultrasound system for percutaneous nephrolithotomy: analysis of 16 cases].
AB - OBJECTIVE: To evaluate the feasibility and efficacy of percutaneous renal
puncture in percutaneous nephrolithotomy guided by novel needle-tracking
ultrasound system. METHODS: From may to october 2013, 16 cases of percutaneous
nephrolithotomy were performed under the guidance of ultrasound system. The
clinical data including the time of completing percutaneous renal puncture, the
color of urine sucked out from the kidney calices, and the complications were
analyzed retrospectively. RESULTS: Of the 16 patients, 18 percutaneous renal
access were established guided by ultrasound system. All of them were successtul
for the first time, and the average time of completing percutaneous renal
punctures was (26.90 +/- 11.37) s (15 to 54 s). After the operation, the
hemoglobin decreased by (9.56 +/- 5.27)%(1.41% to 24.06%), and no complications
occurred except for postoperative fever in 2 case. CONCLUSION: The novel
ultrasound system is a safe and effective technique that can reduce the technical
difficulty of percutaneous renal puncture in percutaneous nephrolithotomy.
PMID- 25131472
TI - [Analysis for risk factors of systemic inflammatory response syndrome after one
phase treatment for apyrexic calculous pyonephrosis by percutaneous
nephrolithotomy].
AB - OBJECTIVE: To investigate the risk factors of systemic inflammatory response
syndrome (SIRS) after one-phase treatment for apyrexic calculous pyonephrosis by
percutaneous nephrolithotomy (PCNL). METHODS: Clinical data of consecutive
apyrexic calculous pyonephrosis patients who underwent one-stage PCNL from
January 2008 to December 2013 were analyzed retrospectively. The data collected
included white blood cells in urine analysis before surgery, midstream urine
culture, preoperative renal function, using antibiotics time before surgery,
operative time, the number of tracts, intraoperative irrigation peak flow, blood
transfusion, and stone composition. Chi-square, t test and Logistic regression
methods were used for analysis of each factor and SIRS. RESULTS: A total of 182
patients were enrolled in this study and 38 patients developed SIRS (20.88%).
There were no statistically significant differences among white blood cells in
urine analysis (P = 0.483), urine culture positive (P = 0.136), and struvite (P =
0.324) in terms of the incidence of postoperative SIRS. Multivariate Logistic
regression model indicated that risk factors of SIRS for apyrexic calculous
pyonephrosis after one-phase PCNL were renal insufficiency (OR = 5.41, 95% CI
1.84 to 22.64, P = 0.014), operative time (OR = 1.01, 95% CI 1.00 to 1.02, P =
0.024), operative tracts (OR = 3.37, 95% CI -1.92 to 32.55, P = 0.077),
intraoperative irrigation peak flow >=500 mL/min (OR = 45.87,95% CI 4.39 to
231.68, P = 0.007), and blood transfusion (OR = 5.98, 95% CI 1.12 to 46.66, P =
0.043). The protective factor was antibiotics use for more than 3 days (OR =
0.34, 95% CI -3.92 to 12.55, P = 0.047). CONCLUSION: The incidence of SIRS after
one-phase PCNL treatment for apyrexic calculous pyonephrosis was similar to that
of other patients. It is relatively safe and reliable to do this. Preoperative
antibiotics should be used for more than 3 days before surgery. Careful
manipulation is needed to avoid blood transfusion. It is better to shorten the
operative time and to reduce multiple tracts operation. Particularly, irrigation
peak flow >=500 mL/min should be avoided in the circumstance of bleeding or
turbid urine.
PMID- 25131473
TI - [Influence of tension-free midurethral sling surgery on sexual function in women
with stress urinary incontinence].
AB - OBJECTIVE: To investigate the change of the female patients' sexual function
after tension free vaginal tape (TVT) or transobturator suburethral tape (TVT-O)
surgery for stress urinary incontinence (SUI). METHODS: Female sexual function
index (FSFI) was sent to 66 female patients who underwent a TVT/TVT-O surgery at
least 3 months after the operation, to a maximum of 5 years. All The patients
were divided into two groups according to different surgical methods, different
follow-up intervals (more than or less than 1 year) and whether there was
concomitant coital incontinence (CCI) before the operation. The changes of FSFI
scores before and after the operation were compared between the two groups by
multiple covariances analysis. The total score was higher, and the sexual
function was better. RESULTS: In the study, 60 patients answered the
questionnaire, and 51 questionnaires were available. Before surgery, there were
no significant difference between TVT and TVT-O groups in FSFI, age, body mass
index (BMI). As to patients who had TVT/TVT-O surgery, when the influence of the
postoperative period and symptoms accompanying intercourse were corrected, the
two groups had no significant difference in difference of FSFI (dFSFI) scores
after operation (F = 2.52, P = 0.119), and they had similar sexual function
improvement ratio (40.0% vs. 44.4%, P > 0.05). But to the patients who had
concomitant coital incontinence before the operations, the dFSFI scores was
higher than patients who did not have concomitant coital incontinence (1.86 +/-
1.95 vs. -0.09 +/- 2.24, P < 0.05). CONCLUSION: TVT and TVT-O surgery have no
significant difference in influence on sexual function in women between each
other, but the patients who suffer from CCI before the surgery will have a better
sexual function improvement.
PMID- 25131474
TI - [Management of female urethral obliteration with the rotary excision appliance].
AB - OBJECTIVE: To describe a new technique using the rotary excision appliance for
the treatment of female urethral obliteration and to evaluate the effect of the
management. METHODS: Between October 2000 and July 2013, 5 cases of female
urethral obstruction (age from 23 to 65 years, time to treatment from 3 to 60
months, obliteraion length from 0.5 to 1.8 cm) were managed using the rotary
excision appliance and the patients had been followed up. RESULTS: After a mean
of 32.4 months (range: 5 to 75 months) of follow-up, normal micturation had been
achieved in all the patients. The maximal urinary flow rate (MFR) ranged from 15
to 28 mL/s (mean 20.6 mL/s). Three patients were continent and 2 patients had
slight incontinence. CONCLUSION: The rotary excision appliance is a useful
instrument for the management of female urethral obliteration. Our Long-term
follow-up provides further support for use of this technique by demonstrating
that urethral continuity can be established without increased incidence of
stricture formation or incontinence.
PMID- 25131475
TI - Chinese urologists' practice patterns of diagnosing and treating chronic pelvic
pain syndrome: a questionnaire survey.
AB - OBJECTIVE: To investigate the application of the Chinese Urological Association
(CUA) guidelines on prostatitis and the effects on the clinical practice patterns
of diagnosing and treating chronic pelvic pain syndrome (CPPS) among Chinese
urologists. METHODS: We conducted a questionnaire investigation of the CUA
guidelines on prostatitis among the urologists from 399 hospitals in 63 cities of
China, and performed statistical analyses on all the eligible questionnaires
collected. RESULTS: Of the 2 251 questionnaires distributed, 2 046 (90.9%) were
eligible, of which 92.5% were from the urologists in tertiary or secondary
hospitals, of whom 72.3% had senior or intermediate professional titles, and
90.2% had studied the CUA guidelines. Most respondents agreed that Type III
prostatitis was a clinical syndrome, of which the diagnosis should be made after
other conditions with similar symptoms had been ruled out and the aim was to
relieve pain, alleviate urination symptoms and improve quality of life. Those who
had and those who had not studied the CUA guidelines differed in their viewpoints
on CPPS as illustrated in the guidelines. In clinical practice, the most common
treatment options for CPPS were pharmaceutical therapy (95.0%), life style
adjustment (88.9%), and psychotherapy (79.9%), and the most frequently prescribed
drugs were phytotherapy (84.5%), alpha-blockers (79.0%) and antibiotics (64.0%).
CONCLUSION: CUA guidelines on prostatitis has gained a nationwide application and
promoted the standardization of the management of CPPS in China.
PMID- 25131476
TI - [Anaplastic lymphoma kinase fusion gene expression, clinical pathological
characteristics and prognosis in 95 Chinese patients with non-small cell lung
cancer].
AB - OBJECTIVE: To examine the prevalence of anaplastic lymphoma kinase (ALK) fusion
gene in Chinese patients with non-small cell lung cancer (NSCLC). METHODS: In
this study, 95 patients with NSCLC and corresponding clinical information and
formalin-fixed paraffin-embedded (FFPE) tissue blocks were included. Hematoxylin
& eosin (HE) staining, conventional ALK immunochemistry (IHC) staining and
intercalated antibody-enhanced polymer (iAEP) IHC staining, and dual-color split
fluorescence in situ hybridization (FISH) for ALK fusion gene were performed.
RESULTS: Eight ALK-positive cases were detected using anti-ALK
immunohistochemistry with the iAEP method, and FISH analyses revealed 4 patients
of them who harbored the ALK fusion gene (4.2%, 4/95), including 2 cases of
female patients with solid signet-ring cell adenocarcinoma and 2 cases of male
patients with adenosquamous carcinoma. The positive cases were all non-smokers
without EGFR/KRAS mutations. Furthermore, the positive cases all survived, and
the overall postsurgery survival time of 2 cases was more than 5 years.
CONCLUSION: ALK IHC with the iAEP method is better than conventional ALK IHC, and
the percentage of the positive cells is more important than that of the
intensity. ALK translocations were infrequent in the entire NSCLC patient
population (<5%) with better prognosis.
PMID- 25131477
TI - [Relationship of genetic variants and cardiovascular risk factors with
interleukin-6 and interleukin-10 secreted by monocytes].
AB - OBJECTIVE: To examine the relationship of interleukin (IL)-6 and IL-10 genetic
variants and cardiovascular factors [oxygenized low density lipoprotein (ox-LDL),
lower physical activity, overweight, etc.] with IL-6 and IL-10 secreted by
monocytes. METHODS: In the study, 40 health persons, aged from 51 to 80 years,
without stroke and myocardial infarction, were randomly sampled from a community
based population in Beijing in 2010. Their data on smoking, drinking, blood
pressure, fasting glucose, and lipid were collected. The single nucleotide
polymorphisms (SNPs) of IL-6 (rs1800796, rs1524107, rs2066992) and IL-10
(rs1800872, rs1554286, rs3021094) were genotyped. The human monocytes were
cultivated in RPMI 1640 medium for 24 h; then divided into two equal parts, in
which ox-LDL (50 mg/L) and phosphate buffer solution (PBS) were added for another
48 h. Finally, the secretions of IL-6 and IL-10 in the culture supernatants were
measured with ELISA. RESULTS: Paired Wilcoxon tests showed that the IL-6, IL-10,
and IL-6/IL-10 were significantly higher in ox-LDL medium than in PBS one (all P
< 0.01). The concentrations in PBS/ox-LDL taken as repeated measurements, and
adjusted for age and gender, the repeated general linear models showed: IL-10 was
significantly lower for those overweight (BMI >= 26 kg/m(2)) than for those
normal weight (P = 0.007), and IL-6/IL-10 was significantly higher in those
overweight (P = 0.003). The IL-6/IL-10 was significantly higher in those with
lower physical activity [metabolic equivalent of energy, METS < 166 kJ/(kg.d)]
than those with higher physical activities (P = 0.046). IL-6 and IL-10 were
significantly higher in alcohol drinkers (P = 0.049 and P = 0.006). IL-6 was
significantly higher in those with higher high-density lipoprotein-cholesterol
(HDL-c, >= 56.4 mg/dL, P = 0.027). There were significant interactions between IL
10 SNPs and ox-LDL on IL-10 (all P < 0.05), but no significant interactions
between IL-6 gene SNPs and ox-LDL on IL-6. CONCLUSION: The ox-LDL together with
lower physical activity and overweight shifts the balance of pro-inflammatory and
anti-inflammatory in the direction of pro-inflammatory. The interaction between
IL-10 gene and ox-LDL is intensively correlated with the secretion of the anti
inflammatory cytokine IL-10.
PMID- 25131478
TI - [Speckle tracking analysis of left atrial phasic function in patients with
hypertension].
AB - OBJECTIVE: To assess left atrial (LA) phasic function in hypertension (HT) and to
evaluate its relationship with left ventricular diastolic function. METHODS:
Cross-sectional data of 738 population (149 non-HT as control, and 589 HT were
further grouped into normal left ventricular diastolic function, mild diastolic
dysfunction and moderate/severe diastolic dysfunction sub-groups) in an urban
community of Beijing were used. LA global longitudinal strain in late diastole
(Sa), early diastole (Se), and total strain (Stot = Sa+ Se), strain rate in late
diastole (SRa), systole (SRs), and early diastole (SRe) were measured using off
line speckle-tracking echocardiography analyzing software, and were compared
between non-HT and HT groups, and among HT sub-groups. RESULTS: LA reservoir
[Stot: 22.7% +/- 5.9% vs. 21.0% +/- 5.8%, P = 0.002; SRs: (1.1 +/- 0.3)/s vs.
(1.0 +/- 0.3)/s, P = 0.033] and conduit [Se: 11.1% +/- 4.8% vs. 9.6% +/- 4.2%, P
= 0.001; SRe: (1.0 +/- 0.4)/s vs. (0.9 +/- 0.3)/s, P < 0.001] indexes were
reduced significantly in HT, while contraction (Sa & SRa) indexes were similar to
those of non-HT. CONCLUSION: LA reservoir and conduit functions are impaired in
HT and deteriorate with left ventricular diastolic dysfunction. LA contraction is
preserved in HT with normal and mild diastolic dysfunction while impaired in
moderate/severe diastolic dysfunction.
PMID- 25131479
TI - [Cardioprotective effect and mechanism of intensive lipid modulation on patients
with coronary artery disease undergoing noncardiac surgery].
AB - OBJECTIVE: To explore the protective effect and possible mechanism of intensive
lipid modulation on the perioperative period of patients with stable coronary
artery disease undergoing noncardiac surgery. METHODS: In the study, 60 patients
with stable coronary artery disease undergoing elective noncardiac surgery were
randomly divided into intensive lipid modulation group (n = 30) and conventional
group (n = 30). In intensive lipid modulation group, the patients were given
atorvastatin 40 mg every night before surgery, 80 mg 12 h before surgery, and 40
mg 2 h before surgery, and 40 mg every night after noncardiac surgery. In
conventional group, the patients were given atorvastatin 20 mg every night before
surgery and also after the surgery. The occurrence of perioperative major adverse
cardiac events (including sudden cardiac death, acute myocardial infarction,
unplanned revascularization) were compared in the two groups. Preoperative and 48
h postoperative changes of lipid levels and inflammatory markers were also
compared in the two groups. RESULTS: In conventional group, one patient suffered
myocardial infarction with acute anterior ST-segment elevation and was given
emergency left anterior descending artery interventional reperfusion therapy, and
7 patients suffered asymptomatic myocardial infarction. In intensive lipid
modulation group, one patient suffered asymptomatic myocardial infarction, and
the incidence rate of perioperative acute myocardial infarction reduced
significantly compared with conventional group (P < 0.05). There was no
significant difference in preoperative and postoperative changes of lipid levels
in the two groups (P > 0.05), and compared with conventional group, there was
significantly lower levels of inflammatory markers in intensive lipid modulation
group (P < 0.05). CONCLUSION: The intensive lipid modulation group significantly
reduced the incidence of perioperative major adverse cardiac events especially
asymptomatic myocardial infarction, and the inhibition of the inflammatory
response may be one of the protective mechanisms, which still needs to be further
confirmed by large multicenter randomized controlled clinical trials.
PMID- 25131480
TI - [Clinical observation of middle cerebral artery angioplasty in treatment of
subcortex cerebral watershed infarction with moderate or severe disabilities].
AB - OBJECTIVE: To assess the safety and effectiveness of middle cerebral artery
angioplasty in treatment of subcortical watershed infarcts (S-CWI) with moderate
or severe disabilities. METHODS: From June 2011 to May 2012, 5 S-CWI patients
(six lesions) with moderate or severe disabilities combining severe stenosis in
Ipsilateral middle cerebral artery received middle cerebral artery angioplasty in
Interventional Radiology and Vascular Surgery Department, Peking University Third
Hospital. We observed the neurological score before and after angioplasty and
assessed the improvement of neurological functions. RESULTS: The National
Institute of Health stroke scale(NIHSS) scores were decreased by 4-6 points and
modified Rankin scale(mRs) scores were decreased 1 point in 7 days. In the 3
months' follow-up, 4 patients' mRs scores were 1 point, and 1 patient's was 2
points. In the 1-year follow-up, there were no new strokes and instent restenosis
events. CONCLUSION: Middle cerebral artery angioplasty in treatment of S-CWI with
moderate or severe disabilities is beneficial.
PMID- 25131481
TI - [Controlled clinical study of trigeminal ganglion puncture guided by CT/MRI image
fusion interface navigation].
AB - OBJECTIVE: To build the radio-frequency thermocoagulation (RFT) interface under
navigation including foramen ovale and trigeminal ganglion based on CT/MRI image
fusion technology, to visualize the relationship between the trigeminal ganglion
and the puncture needle, and to observe clinical effects of this method. METHODS:
CT and MRI data of 20 trigeminal neuralgia patients which were input into
BrainLAB-iPlan navigation planning system, were aligned and merged, so that the 3
dimentional image fusion interface of CT and MRI for puncture was built.
According to the image fusion interface, the pathways targeting the trigeminal
ganglion were planned to assist trigeminal ganglion puncture and RFT. The
treatment consequences were observed and compared with 20 patients under the RFT
only with the direction of pre- and intra-operative CT. RESULTS: In the group of
CT/MRI image fusion cases, 3 cases had been predicted to be difficult because of
unreachable ganglion through the foramen ovale pathway. The postoperative
clinical examination proved that the ganglions of these 3 cases were only
insufficiently damaged or undamaged. The other 17 cases proved better results,
except 2 cases whose treatment was changed in operation. The valid rates for both
image fusion navigation group and CT group were all above 95%. CONCLUSION:
Navigation interface including both foramen ovale and trigeminal ganglion based
on CT/MRI image fusion made visualization of the pathway targeting ganglion come
true, which made the treatment more accurate and individual. Whether the pathway
could reach the ganglion might distinguish the trouble cases from others.
PMID- 25131482
TI - [Amplicon density-weighted algorithms for analyzing dissimilarity and dynamic
alterations of RAPD polymorphisms of Cordyceps sinensis].
AB - OBJECTIVE: To examine the dynamic maturational alterations of random amplified
polymorphic DNA (RAPD) molecular marker polymorphism resulted from differential
expressions of multiple fungi in the caterpillar body, stroma and ascocarp
portion of Cordyceps sinensis (Cs). METHODS: Used the fuzzy, integral RAPD
molecular marker polymorphism method with 20 random primers; used density
weighted cluster algorithms and ZUNIX similarity equations; compared RAPD
polymorphisms of the caterpillar body, stroma and ascocarp of Cs during
maturation; and compared RAPD polymorphisms of Cs and Hirsutella sinensis (Hs).
RESULTS: Density-unweighted algorithms neglected the differences in density of
the DNA amplicons. Use of the density-weighted ZUNIX similarity equations and the
clustering method integrated components of the amplicon density differences in
similarity computations and clustering construction and prevented from the loss
of the information of fungal genomes. An overall similarity 0.42 (< the overall
dissimilarity 0.58) was observed for all compartments of Cs at different
maturation stages. The similarities for the stromata or caterpillar bodies of Cs
at 3 maturational stages were 0.57 or 0.50, respectively. During Cs maturation,
there were dynamic Low->High->Low alterations of the RAPD polymorphisms between
stromata and caterpillar bodies dissected from the same pieces of Cs. The
polymorphic similarity was the highest (0.87) between the ascocarp and mature
stroma, forming a clustering clade, while the premature stroma and caterpillar
body formed another clade. These 2 clades merged into one cluster. Another clade
containing the maturing stroma and caterpillar body merged with mature
caterpillar body, forming another cluster. The RAPD polymorphic similarities
between Hs and Cs samples were 0.55-0.69. Hs were separated from Cs clusters by
the out-group control Paecilomyces militaris. CONCLUSION: The wealthy RAPD
polymorphisms change dynamically in the Cs compartments with maturation. The
different RAPD polymorphism for Hs from those for Cs supports the hypothesis of
integrated micro-ecosystem Cs with multiple fungi, but does not support the
"single fungal species" hypothesis for Cs and the anamorph-teleomorph connection
between Hs and Cs.
PMID- 25131483
TI - [Preparation and property study of doxorubicin loaded microspheres].
AB - OBJECTIVE: To prepare doxorubicin-loaded polyvinylalcohol-acrylic acid (PVA-AA)
microspheres and evaluate properties of this chemoembolic agent. METHODS: PVA-AA
microspheres were synthesized by inverse suspension polymerization method and
then verified by infrared spectroscopy. drug loading (DL) and entrapment
efficiency (EE%) were measured after doxorubicinwas loaded on PVA-AA
microspheres. Their morphology and elasticity were investigated by optical
microscope, environmental scanning electron microscope and texture analyzer,
respectively. T-cell apparatus was used to evaluate the in vitro release behavior
of doxorubicin-loaded microspheres.The external carotid of the rabbit was chosen
as an embolization site to evaluate the in vivo embolic property of the
microspheres. RESULTS: PVA-AA microspheres, which were transparent spheres,turned
into red spheres after doxorubicin loading. DL of the microspheres was (20.56 +/-
0.69)g/L and (23.25 +/- 0.27) g/L,and EE% was 82.22% +/- 2.76% and 93.00% +/-
1.06% within 20 min and 6 h, respectively. The in vitro release results showed a
significantly delayed release of the drug for 10.32% +/- 0.47% after 24 h. The
Young's modulus was (178.30 +/- 12.33) kPa and (213.29 +/- 15.61) kPa for blank
microspheres and doxorubicin-loaded microspheres, respectively. Both blank
microspheres and doxorubicin-loaded microspheres exhibited good elasticity. In
vivo embolization showed that 0.3 mL of microspheres could produce distal embolic
efficiency. CONCLUSION: The doxorubicin-loaded microspheres are expected to be a
promising new chemoembolic agent.
PMID- 25131484
TI - [A prospective randomized control study: new rigid cystoscopy technology to
improve patients' comfort].
AB - OBJECTIVE: To determine whether the extruded irrigation solution bag during
passage of rigid cystoscope will reduce the patient's discomfort. METHODS: In the
study, 378 male patients undergoing rigid cystoscopies were randomized into
"Institute of Urology Peking University (IUPU)" technique group (n = 193) and
routine manipulation group (n = 185). All the patients had received 10 mL
oxybuprocaine gel before manipulation. In the IUPU technique group, irrigation
solution bag was connected with cystoscope sheath and obturator. As the scope
passed through the bulbar urethra, a nurse was instructed to extrude the
irrigating fluid bag. A 10-point visual analog pain scale assessment was
completed by the patient after the procedure. RESULTS: The visual analog pain
score was 2 (1-2) in the IUPU technique group and 4 (3-6) in the routine
manipulation group (P < 0.001, Mann-Whitney U test). All the procedure
indications had no effect on the findings. CONCLUSION: This study has shown that
a simple IUPU technique can significantly reduce the patient's discomfort during
outpatient rigid cystoscopy. We strongly recommend this technique for all male
patients undergoing rigid cystoscopy.
PMID- 25131485
TI - [Transabdominal laparoscopic radical nephrectomy of modified Pfannenstiel
incision].
AB - OBJECTIVE: To evaluate the efficacy and safety of transperitoneal laparoscopic
radical nephrectomy with the modified Pfannenstiel incision. METHODS: Between
Aug. 2012 and Jul. 2013, the same surgeon performed transperitoneal laparoscopic
radical nephrectomy for 12 patients with renal masses. The approach was usually
performed through 3 ports or 4 ports placed in a traditional manner. After
laparoscopic radical nephrectomy was completed, and the specimen was entrapped in
a specimen retrieval bag, a 7 cm modified Pfannenstiel skin incision was made
over the symphysis pubis, lateralized slightly toward the side of surgery.
RESULTS: All the procedures were completed without conversion to open radical
nephrectomy. The operative time was 106 to 234 minutes and the blood loss was
minimal. There was no intra- or post-operative complications. The pathological
result was renal cell carcinoma. One patient died of multiple organ metastasis
after 5 months. No recurrence was seen after 9 to 20 months' follow-up.
CONCLUSION: Laparoscopic radical nephrectomy with the modified Pfannenstiel
incision where the kidney is removed offers the benefits of improved cosmesis
over the traditional muscle-cutting extension of an upper abdominal, lateral port
site. The modified Pfannenstiel incision combines the advantages of a low
abdominal incision and improved cosmesis, and can be considered a potential
alternative for traditional laparoscopic nephrectomy.
PMID- 25131486
TI - [Micropump infusion of gonadorelin in the treatment of hypogonadotropic
hypogonadism in patients with pituitary stalk interruption syndrome: cases
analysis and literature review].
AB - Two cases of hypogonadotropic hypogonadism caused by pituitary stalk interruption
syndrome treated by pulse infusion of gonadorelin via micropump were reported,
and their clinical features and the treatment process of pulse infusion of
gonadorelin via micropump summarized. Both of the 2 patients were presented
primarily with hypogonadotropic hypogonadism. After the treatment with pulse
infusion of gonadorelin via micropump, their syndrome of androgen deficiency
improved and the gonadotropin levels promoted at the end of 12 weeks' follow-up.
Pulse infusion of gonadorelin via micropump is an alternative to treat
hypogonadotropic hypogonadism caused by pituitary stalk interruption syndrome.
PMID- 25131487
TI - [Leucine-rich glioma inactivated-1 protein antibody associated limbic
encephalitis: one case report].
AB - OBJECTIVE: To report a case of leucine-rich glioma inactivated-1 protein antibody
(LGI1-Ab) associated limbic encephalitis. METHODS: A 76-year-old woman was
admitted to the hospital because of cognitive impairment and faciobrachial
dystonic seizures for six months. Hyponatremia was also noted in this patient.
Antibodies to the LGI1 were positive.(18)F-FDG uptake was measured on the PET-CT
scans of this patient. RESULTS: PET-CT showed bilateral putamen hypermetabolism
with hypometabolism in other regions. Her symptoms were improved after
intravenous immunoglobulin therapy. CONCLUSION: LGI1-Ab associated encephalitis
can manifest as basal ganglia hypermetabolism and faciobrachial dystonic
seizures.
PMID- 25131488
TI - [Retroperitoneal laparoscopic partial nephrectomy for treatment of cystic
nephroma: one case report].
AB - The clinical features and pathologic findings of one case of cystic nephroma was
reported,and the safety of treatment by retroperitoneal laparoscopic partial
nephrectomy evaluated. The patient was a 20-year-old woman, and found left renal
cyst for 1 year with pain in her left flank one month ago. The patient was
diagnosed as complex renal cyst, then underwent retroperitoneal laparoscopic
partial nephrectomy. In the operation, the tumor was located in the middle and
lower part of her left kidney, with a number of small sample masses, and a solid
mass near the renal parenchymal part. The operation time was 224 min, and the
artery occlusion time was about 17 min. The blood loss was 20 mL, with no blood
transfusion. The pathology was cystic nephroma. No operation complication was
seen, nor was recurrence after a short-term follow-up. Cystic nephroma is a
relatively rare benign lesion of the kidney. Retroperitoneal laparoscopic partial
nephrectomy is a safe and effective way to treat cystic nephroma.
PMID- 25131489
TI - [Use of abiraterone acetate in the treatment of patients with metastatic
castration resistant prostate cancer and no prior chemotherapy: 3 case reports
and literature review].
AB - OBJECTIVE: To evaluate the safety and efficiency of using abiraterone and
prednisone in the treatment of patient with metastatic castration resistant
prostate cancer (mCRPC) no prior chemotherapy. METHODS: Three mCRPC no prior
chemotherapy patients accepted abiraterone and prednisone treatment. The clinical
data were analyzed retrospectively and the safety and efficiency of this
treatment option were discussed. The Gleason scores of the three mCRPC patients
were 5, 9, and 9. The clinical stages were T3aNxM0, T3aNxM1b, and T3aNxM1b. The
patients received abiraterone 1 000 mg daily and prednisone 5 mg twice daily and
androgen deprivation therapy in the treatment. Their blood pressure, complete
blood count, prostate specific antigen (PSA), biochemical parameters, whole body
CT scan and bone scan were done regularly to monitor the progression of the
diseases. RESULTS: In this study, the general condition improved in two patients.
Two of the three patients experienced decrease of PSA and no progression. One
patient experienced disease progression. Generally, abiraterone and prednisone
resulted in prolonged radiographic progression-free survival and delayed in PSA
progression in mCRPC no prior chemotherapy. There were no severe side effects,
such as hypokalemia, hypertension, and water-sodium retention. The patient's
tolerance was good. CONCLUSION: Abiraterone and prednisone are safe and can
improve mCRPC no prior chemotherapy patient's life quality and may prolong the
overall survival.
PMID- 25131490
TI - [Balloon dilation by B ultrasound monitoring for treatment of urethral stricture:
5 case reports].
AB - Urethral stricture is a common urologic disease and there are many therapeutic
methods for it. Here we investigated the application of balloon dilation under B
mold ultrasound monitoring in the treatment of urethral stricture. Five male
patients suffering from urethral stricture were treated with balloon dilation
under B-mold ultrasound monitoring.Their urination was assessed after operation.
All the patients underwent the operation successfully, without serious
complications. The urinary catheter was removed 3-4 weeks after operation. The
patients were followed up for 8 to 15 months. Four patients were voiding well and
one improved. Balloon dilation under B-mold ultrasound monitoring in the
treatment of urethral stricture was intuitive, safe and effective.
PMID- 25131491
TI - [Paroxysmal kinesigenic dyskinesia: 2 case reports].
AB - Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological condition in which
brief and frequent dyskinetic attacks are provoked by sudden movement. PKD is
more common in men and can be idiopathic (commonly familial) or due to a variety
of causes. The pathophysiology of PKD is uncertain but it could be an ion-channel
disorder. Genetic linkage studies have isolated several loci on chromosome 16,
and proline-rich transmembrane protein 2 (PRRT2) has been identified as a
causative gene of PKD by using a combination of exome sequencing and linkage
analysis. Antiepileptic drugs, particularly, carbamazepine are very helpful in a
large proportion of cases. Sometimes it can be difficult to distinguish this
syndrome from epilepsy. We reported 2 patients who presented abnormal involuntary
attack. Evaluations included general physical examinations, endocrinologic and
metabolic studies, video electroencephalograms and brain MRI imaging. All of
these studies were normal. All of symptoms showed excellent response to
carbamazepine.
PMID- 25131492
TI - Sensitive determination of carbidopa through the electrochemiluminescence of
luminol at graphene-modified electrodes.
AB - Using the concept of electrogenerated chemiluminescence (ECL), a sensitive
analytical method for the determination of carbidopa is described. Electro
oxidation of carbidopa on the surface of a graphene oxide (GO)-modified gold
electrode (GE) leads to enhancement of the weak emission of oxidized luminol.
Under optimum experimental conditions, the ECL signal increases linearly with
increasing carbidopa concentrations over a range of 1.0 * 10(-9) -1.7 * 10(-7)
M, with a detection limit of 7.4 * 10(-10) M. The proposed ECL method was
successfully used for the determination of carbidopa in urine samples.
PMID- 25131493
TI - Significant factors in family difficulties for fathers and mothers who use
support services for children with hikikomori.
AB - AIMS: Hikikomori is a new psychosociological phenomenon among youth, of almost
complete withdrawal from social interaction, and it has received considerable
attention in community mental health in Japan. The aims of the present study were
to identify the influential factors of family difficulties of parents who use
support services for children with hikikomori, and compare them between fathers
and mothers. METHODS: Data were collected from 110 parents (55 couples) of
children with hikikomori with regard to family difficulties, quality of life, and
depression variables via self-report questionnaires. To assess the influential
factors of Family Difficulties for parents with children with hikikomori,
hierarchical multiple linear regression analysis was carried out for gender.
RESULTS: While 94.5% of mothers received some kind of family support, only 61.9%
of fathers received it. For both genders, the number of services that the fathers
received was significantly correlated with marital cooperation, and the number of
services that the mothers received was significantly correlated with support
resource utilization. CONCLUSIONS: It is necessary for fathers to receive more
support, and it is important for professionals to encourage parents to address
their difficulties together.
PMID- 25131494
TI - The role of influenza in the severity and transmission of respiratory bacterial
disease.
AB - Infections with influenza viruses and respiratory bacteria each contribute
substantially to the global burden of morbidity and mortality. Simultaneous or
sequential infection with these pathogens manifests in complex and difficult-to
treat disease processes that need extensive antimicrobial therapy and cause
substantial excess mortality, particularly during annual influenza seasons and
pandemics. At the host level, influenza viruses prime respiratory mucosal
surfaces for excess bacterial acquisition and this supports increased carriage
density and dissemination to the lower respiratory tract, while greatly
constraining innate and adaptive antibacterial defences. Driven by virus-mediated
structural modifications, aberrant immunological responses to sequential
infection, and excessive immunopathological responses, co-infections are noted by
short-term and long-term departures from immune homoeostasis, inhibition of
appropriate pathogen recognition, loss of tolerance to tissue damage, and general
increases in susceptibility to severe bacterial disease. At the population level,
these effects translate into increased horizontal bacterial transmission and
excess use of antimicrobial therapies. With increasing concerns about future
possible influenza pandemics, the past decade has seen rapid advances in our
understanding of these interactions. In this Review, we discuss the
epidemiological and clinical importance of influenza and respiratory bacterial co
infections, including the foundational efforts that laid the groundwork for
today's investigations, and detail the most important and current advances in our
understanding of the structural and immunological mechanisms underlying the
pathogenesis of co-infection. We describe and interpret what is known in
sequence, from transmission and phenotypic shifts in bacterial dynamics to the
immunological, cellular, and molecular modifications that underlie these
processes, and propose avenues of further research that might be most valuable
for prevention and treatment strategies to best mitigate excess disease during
future influenza pandemics.
PMID- 25131495
TI - Development and validation of a microRNA based diagnostic assay for primary tumor
site classification of liver core biopsies.
AB - Identification of the primary tumor site in patients with metastatic cancer is
clinically important, but remains a challenge. Hence, efforts have been made
towards establishing new diagnostic tools. Molecular profiling is a promising
diagnostic approach, but tissue heterogeneity and inadequacy may negatively
affect the accuracy and usability of molecular classifiers. We have developed and
validated a microRNA-based classifier, which predicts the primary tumor site of
liver biopsies, containing a limited number of tumor cells. Concurrently we
explored the influence of surrounding normal tissue on classification. MicroRNA
profiling was performed using quantitative Real-Time PCR on formalin-fixed
paraffin-embedded samples. 278 primary tumors and liver metastases, representing
nine primary tumor classes, as well as normal liver samples were used as a
training set. A statistical model was applied to adjust for normal liver tissue
contamination. Performance was estimated by cross-validation, followed by
independent validation on 55 liver core biopsies with a tumor content as low as
10%. A microRNA classifier developed, using the statistical contamination model,
showed an overall classification accuracy of 74.5% upon independent validation.
Two-thirds of the samples were classified with high-confidence, with an accuracy
of 92% on high-confidence predictions. A classifier trained without adjusting for
liver tissue contamination, showed a classification accuracy of 38.2%. Our
results indicate that surrounding normal tissue from the biopsy site may
critically influence molecular classification. A significant improvement in
classification accuracy was obtained when the influence of normal tissue was
limited by application of a statistical contamination model.
PMID- 25131499
TI - Prevalence and risk factors for diabetic retinopathy in the 40 to 80 year-old
population in Yazd, Iran: the Yazd Eye Study.
PMID- 25131496
TI - Acid ceramidase is associated with an improved prognosis in both DCIS and
invasive breast cancer.
AB - Acid ceramidase (ASAH1) a key enzyme of sphingolipid metabolism converting pro
apoptotic ceramide to sphingosine has been shown to be overexpressed in various
cancers. We previously demonstrated higher expression of ASAH1 in ER positive
compared to ER negative breast cancer. In the current study we performed subtype
specific analyses of ASAH1 gene expression in invasive and non invasive breast
cancer. We show that expression of ASAH1 is mainly associated with luminal A -
like cancers which are known to have the best prognosis of all breast cancer
subtypes. Moreover tumors with high ASAH1 expression among the other subtypes are
also characterized by an improved prognosis. The good prognosis of tumors with
high ASAH1 is independent of the type of adjuvant treatment in breast cancer and
is also detected in non small cell lung cancer patients. Moreover, even in pre
invasive DCIS of the breast ASAH1 is associated with a luminal phenotype and a
reduced frequency of recurrences. Thus, high ASAH1 expression is generally
associated with an improved prognosis in invasive breast cancer independent of
adjuvant treatment and could also be valuable as prognostic factor for pre
invasive DCIS.
PMID- 25131498
TI - Having a direct look: analysis of DNA damage and repair mechanisms by next
generation sequencing.
AB - Genetic information is under constant attack from endogenous and exogenous
sources, and the use of model organisms has provided important frameworks to
understand how genome stability is maintained and how various DNA lesions are
repaired. The advance of high throughput next generation sequencing (NGS)
provides new inroads for investigating mechanisms needed for genome maintenance.
These emerging studies, which aim to link genetic toxicology and mechanistic
analyses of DNA repair processes in vivo, rely on defining mutational signatures
caused by faulty replication, endogenous DNA damaging metabolites, or exogenously
applied genotoxins; the analysis of their nature, their frequency and
distribution. In contrast to classical studies, where DNA repair deficiency is
assessed by reduced cellular survival, the localization of DNA repair factors and
their interdependence as well as limited analysis of single locus reporter
assays, NGS based approaches reveal the direct, quantal imprint of mutagenesis
genome-wide, at the DNA sequence level. As we will show, such investigations
require the analysis of DNA derived from single genotoxin treated cells, or DNA
from cell populations regularly passaged through single cell bottlenecks when
naturally occurring mutation accumulation is investigated. We will argue that the
life cycle of the nematode Caenorhabditis elegans, its genetic malleability
combined with whole genome sequencing provides an exciting model system to
conduct such analysis.
PMID- 25131501
TI - WITHDRAWN: Who are the patients with extrapulmonary tuberculosis?
AB - This article has been withdrawn for editorial reasons because the journal will be
published only in English. In order to avoid duplicated records, this article can
be found at http://dx.doi.org/10.1016/j.rppnen.2014.06.010. The Publisher
apologizes for any inconvenience this may cause. The full Elsevier Policy on
Article Withdrawal can be found at
http://www.elsevier.com/locate/withdrawalpolicy.
PMID- 25131500
TI - Sirtuin inhibitor Ex-527 causes neural tube defects, ventral edema formations,
and gastrointestinal malformations in Xenopus laevis embryos.
AB - Chemical reagent Ex-527 is widely used as a major inhibitor of Sirtuin enzymes,
which are a family of highly conserved protein deacetylases and have been linked
with caloric restriction and aging by modulating energy metabolism, genomic
stability, and stress resistance. However, the extent to which Ex-527 controls
early developmental events of vertebrate embryos remains to be understood. Here,
we report an examination of Ex-527 effects during Xenopus early development,
followed by a confirmation of expressions of xSirt1 and xSirt2 in embryonic
stages and enhancement of acetylation by Ex-527. First, we found that reductions
in size of neural plate at neurula stages were induced by Ex-527 treatment.
Second, tadpoles with short body length and large edematous swellings in the
ventral side were frequently observed. Moreover, Ex-527-treated embryos showed
severe gastrointestinal malformations in late tadpole stages. Taken together with
these results, we conclude that the Sirtuin family start functioning at early
embryonic stages and is required for various developmental events.
PMID- 25131502
TI - WITHDRAWN: Bronchial-pulmonary adenocarcinoma subtyping relates with different
molecular pathways.
AB - This article has been withdrawn for editorial reasons because the journal will be
published only in English. In order to avoid duplicated records, this article can
be found at http://dx.doi.org/10.1016/j.rppnen.2014.05.006. The Publisher
apologizes for any inconvenience this may cause. The full Elsevier Policy on
Article Withdrawal can be found at
http://www.elsevier.com/locate/withdrawalpolicy.
PMID- 25131503
TI - A case for the use of autoethnography in nursing research.
AB - AIMS: This paper discusses the basis for and potential usefulness of
autoethnography as a research method in nursing. BACKGROUND: While qualitative
research in nursing has traditionally involved the researcher taking an objective
stance, autoethnography, with roots in the social sciences, is an emerging method
that examines the researcher's own experience in a cultural context. DESIGN:
Discussion paper. DATA SOURCES: Data sources from 1979-2013 in the CINAHL,
Medline and PsycInfo databases were drawn on including articles from nursing and
social science journals on autoethnography and related narrative-based
approaches. DISCUSSION: Autoethnography is based on the assumption that reality
is multifaceted and the role of culture and context is crucial in understanding
human experience. The reader is engaged through the evocation of emotion and the
stimulation of reflection. IMPLICATIONS FOR NURSING: While autoethnography has
thus far been little used in the discipline of nursing, it is a methodology that
offers novel insights and an opportunity to examine the impact of nurses'
personal and professional cultural identity on their practice. CONCLUSION:
Through the use of a subjective lens, autoethnography gives nurses the
opportunity to tell stories that would otherwise not be heard. It involves a
courageous laying bare of the self to gain new cultural understandings and it
offers the potential for nurses to learn from the experiences and reflections of
other nurses.
PMID- 25131504
TI - Reported side effects of intravenous midazolam sedation when used in paediatric
dentistry: a review.
AB - BACKGROUND: Intravenous (IV) midazolam may be of value as an alternative
paediatric dental sedation technique, but there is some apprehension concerning
its routine use due to a lack of evidence regarding its safety and side effects.
AIM: To review all available literature reporting the side effects of IV
midazolam in children undergoing dental procedures. DESIGN: Both randomised
controlled trials (RCT) and non-randomised studies were reviewed. Reported side
effects were categorised as either significant or minor, and the percentage
prevalence of significant or minor side effects per episode of treatment was
calculated. RESULTS: Five RCTs were included, in which no significant side events
were reported; however, minor side effects were recorded (n = 33, 19.5%), with
paradoxical reaction being the most common (n = 11, 6.5%). Six non-randomised
studies were included, in which no significant side effects were reported;
however, minor side effects were reported (n = 118, 16.8%) with paradoxical
reaction being the most common (n = 89, 12.7%). CONCLUSIONS: Although no
significant side effects were recorded, of the minor side effects reported
paradoxical reaction was the most common. Due to inconsistency in side effect
reporting, the authors suggest the application of a standardised adverse event
reporting tool for future studies of sedation in paediatric dentistry.
PMID- 25131505
TI - Daytime light exposure: effects on biomarkers, measures of alertness, and
performance.
AB - Light can elicit an alerting response in humans, independent from acute melatonin
suppression. Recent studies have shown that red light significantly increases
daytime and nighttime alertness. The main goal of the present study was to
further investigate the effects of daytime light exposure on performance,
biomarkers and measures of alertness. It was hypothesized that, compared to
remaining in dim light, daytime exposure to narrowband long-wavelength (red)
light or polychromatic (2568K) light would induce greater alertness and shorter
response times. Thirteen subjects experienced three lighting conditions: dim
light (<5lux), red light (lambdamax=631nm, 213lux, 1.1W/m(2)), and white light
(2568K, 361lux, 1.1W/m(2)). The presentation order of the lighting conditions was
counterbalanced across the participants and each participant saw a different
lighting condition each week. Our results demonstrate, for the first time, that
red light can increase short-term performance as shown by the significant
(p<0.05) reduced response time and higher throughput in performance tests during
the daytime. There was a significant decrease (p<0.05) in alpha power and alpha
theta power after exposure to the white light, but this alerting effect did not
translate to better performance. Alpha power was significantly reduced after red
light exposure in the middle of the afternoon. There was no significant effect of
light on cortisol and alpha amylase. The present results suggest that red light
can be used to increase daytime performance.
PMID- 25131506
TI - The effects of curcumin on depressive-like behavior in mice after
lipopolysaccharide administration.
AB - Current evidence supports that inflammation and increased cytokine levels are
associated with depression-like symptoms and neuropsychological disturbances in
humans. Curcumin has anti-inflammatory, antioxidant and anti-depressant-like
properties. Here, we examined the effects of curcumin on lipopolysaccharide (LPS)
induced depressive-like behavior and inflammation in male mice. A single
administration of LPS (0.83mg/kg, i.p.) increased the immobility time in the
forced swimming test (FST) and tail suspension test (TST), reduced sucrose
consumption without affecting spontaneous locomotor activity. Pretreatment with
curcumin (50mg/kg, i.p.) for 7 consecutive days reversed LPS-induced alterations
in the FST, TST, and sucrose preference test. Moreover, pre-treatment with
curcumin attenuated LPS-induced microglial activation and overproduction of pro
inflammatory cytokine (interleukin-1beta and tumor necrosis factor-alpha), as
well as the levels of inducible nitric oxide synthase and cyclooxygenase-2 mRNA
in the hippocampus and prefrontal cortex (PFC). In addition, curcumin ameliorated
LPS-induced NF-kappaB activation in the hippocampus and PFC. The results
demonstrate that curcumin may be an effective therapeutic agent for LPS-induced
depressive-like behavior, partially due to its anti-inflammatory aptitude.
PMID- 25131508
TI - Treats: low socioeconomic status Australian parents' provision of extra foods for
their overweight or obese children.
AB - ISSUE ADDRESSED: Child obesity is a global issue, with rates highest among
disadvantaged groups. Overconsumption of treats is a contributor to children's
weight problems. The objective of this study was to explore low socioeconomic
parents' beliefs and behaviours relating to their provision of treat foods for
their overweight or obese children. METHODS: Qualitative methods were used to
collect data; these included introspections, interviews and focus groups. A total
of 37 parents of overweight or obese children aged between 5 and 9 years took
part in the 12-month study. RESULTS: Most parents provided their children with
treats on a daily basis. Factors affecting parents' provision of treats included
parents' desire to control their children's behaviour, to demonstrate love and
affection, and to address deprivation beliefs. CONCLUSION: There is considerable
scope for improving these parents' treating behaviours by understanding the
relevant factors underpinning their situations and choices. SO WHAT? The findings
provide an indication of the kinds of health promotion interventions that may be
needed to assist in addressing treating behaviours among disadvantaged parents
with overweight or obese children.
PMID- 25131510
TI - Experimental and theoretical confirmation of the scaling exponent 2 in pyramidal
load displacement data for depth sensing indentation.
AB - A series of articles by Kaupp et al. have recently been published in "Scanning,"
containing erroneous claims about the curvature of pyramidal nanoindentation
loading curves. The present paper recalls the theoretical reasons why, for self
similar indenter shapes like pyramidal or conical indentations, the load scales
with the indentation depth squared. Furthermore, experimental evidence for that
behavior is provided for a wide variety of materials, ranging from ceramics to
metals and polymers.
PMID- 25131509
TI - Liver sinusoidal endothelial cells in hepatic fibrosis.
AB - Capillarization, lack of liver sinusoidal endothelial cell (LSEC) fenestration,
and formation of an organized basement membrane not only precedes fibrosis, but
is also permissive for hepatic stellate cell activation and fibrosis. Thus,
dysregulation of the LSEC phenotype is a critical step in the fibrotic process.
Both a vascular endothelial growth factor (VEGF)-stimulated, nitric oxide (NO)
independent pathway and a VEGF-stimulated NO-dependent pathway are necessary to
maintain the differentiated LSEC phenotype. The NO-dependent pathway is impaired
in capillarization and activation of this pathway downstream from NO restores
LSEC differentiation in vivo. Restoration of LSEC differentiation in vivo
promotes HSC quiescence, enhances regression of fibrosis, and prevents
progression of cirrhosis.
PMID- 25131511
TI - Controlled silica deposition on self-assembled peptide nanostructures via varying
molecular structures of short amphiphilic peptides.
AB - Cationic amphiphilic peptides are highly similar to native silaffins and
silicateins for biosilicification in terms of their composition, amphiphilicity,
and self-assembling propensity. To understand the relationship between organic
molecular structures, molecular self-assembly and silica morphogenesis during
biosilicification, we have prepared a series of short self-assembling peptide
amphiphiles (I3-5K, I4K2, I3-4R, and I4R2) and investigated their capability to
mediate silicification under ambient conditions. I3K self-assembled into tubular
nanofibrils while I4K1-2 and I5K formed solid nanofibrils in aqueous solution
with their outer diameters decreasing as the number of hydrophobic or hydrophilic
amino acid residues increased. Changes in molecular structure thus altered their
self-assembled geometries, and the exposed surfaces and surface lysine densities
under different geometries then played different mediating roles in
silicification, leading to different silica deposition patterns and final silica
nanostructures. The templating capacity was weakened or lost when lysine was
replaced by arginine, despite the fact that I3-4R and I4R2 self-assembled into
nanofibrils and nanoribbons under similar conditions.
PMID- 25131512
TI - Duration of obesity and overweight and risk of type 2 diabetes among US women.
AB - OBJECTIVE: The purpose of this study was to examine the association between
duration of adiposity and risk of type 2 diabetes (T2D) in US women. METHODS:
Nearly 61,821 participants were prospectively followed from the Nurses' Health
Study (1984-2008) and 63,653 participants from Nurses' Health Study II (1991
2011). Participants were considered overweight (BMI 25-30 kg m(-2) ) or obese
(BMI >= 30 kg m(-2) ) if their BMI was above the cutoffs for two successive
assessments. The time-dependent Cox proportional hazard models were used to
assess associations between excess weight duration and T2D risk. RESULTS: In
pooled multivariable analyses of the two cohorts, each two extra years of being
overweight was associated with 9% (RR = 1.09, 95% CI 1.08-1.09) increased risk of
developing T2D. For each 2-year increment in obesity duration, the risk of T2D
was increased by 14% (RR = 1.14, 95% CI 1.14-1.15). Adjustment for current BMI
greatly attenuated the association for obesity duration (RR = 1.02, 95% CI 1.01
1.03), although the attenuation was less for overweight duration (RR = 1.04, 95%
CI 1.04-1.05). CONCLUSIONS: Both overweight and obesity duration were associated
with a significantly higher risk of T2D, and these associations were mainly
explained by current BMI, especially for obesity duration.
PMID- 25131513
TI - The effect of ZnCl2 on green Spanish-style table olive packaging, a presentation
style dependent behaviour.
AB - BACKGROUND: Zinc chloride has been used previously as a preservative in directly
brined olives with promising results. However, this is the first time that the
effects of ZnCl2 addition (0-1 g L(-1) ) on green Spanish-style table olive (cv.
Manzanilla) packaging has been studied. RESULTS: The presence of ZnCl2 affected
the physico-chemical characteristics of the products; the presence of the Zn led
to lower pH values (particularly just after packaging) and titratable and
combined acidity values than the control but did not produce clear trends in the
colour parameters. No Enterobacteriaceae were found in any of the treatments
evaluated. At the highest ZnCl2 concentrations, the lactic acid bacteria were
inhibited while, unexpectedly, its presence showed a lower effect than potassium
sorbate against the yeast population. Regardless of the use of potassium sorbate
or ZnCl2 , the packages had a reduced microbial biodiversity because only
Lactobacillus pentosus and Pichia galeiformis were found at the end of the shelf
life. With respect to organoleptic characteristics, the presentations containing
ZnCl2 were not differentiated from the traditional product. CONCLUSION: Zinc
chloride was less efficient than potassium sorbate as a yeast inhibitor in green
Spanish-style olives, showing clear presentation style dependent behaviour for
this property. Its presence produced significant changes in chemical parameters
but scarcely affected colour or sensory characteristics.
PMID- 25131514
TI - The amnion muscle combined graft (AMCG) conduits: a new alternative in the repair
of wide substance loss of peripheral nerves.
AB - The use of autologous sural nerve grafts is still the current gold standard for
the repair of peripheral nerve injuries with wide substance losses, but with a
poor rate of functional recovery after repair of mixed and motor nerves, a
limited donor nerve supply, and morbidity of donor site. At present, tubulization
through the muscle vein combined graft, is a viable alternative to the nerve
autografts and certainly is a matter of tissue engineering still open to
continuous development, although this technique is currently limited to a
critical gap of 3 cm with less favorable results for motor function recovery. In
this report, we present a completely new tubulization method, the amnion muscle
combined graft (AMCG) technique, that consists in the combination of the human
amniotic membrane hollow conduit with autologous skeletal muscle fragments for
repairing the substance loss of peripheral nerves and recover both sensory and
motor functions. In a series of five patients with loss of substance of the
median nerve ranging 3-5 cm at the wrist, excellent results graded as S4 in two
cases, S3+ in two cases, and S3 in one case; M4 in four cases and M3 in one case
were achieved. No iatrogenic damage due to withdrawal of a healthy nerve from
donor site was observed. This technique allows to repair extensive loss of
substance up to 5 cm with a good sensory and motor recovery. The AMCG thus may be
considered a reasonable alternative to traditional nerve autograft in selected
clinical conditions.
PMID- 25131515
TI - Is evaluative conditioning really resistant to extinction? Evidence for changes
in evaluative judgements without changes in evaluative representations.
AB - Evaluative conditioning (EC) is defined as the change in the evaluation of a
conditioned stimulus (CS) due to its pairing with a positive or negative
unconditioned stimulus (US). Although several individual studies suggest that EC
is unaffected by unreinforced presentations of the CS without the US, a recent
meta-analysis indicates that EC effects are less pronounced for post-extinction
measurements than post-acquisition measurements. The disparity in research
findings suggests that extinction of EC may depend on yet unidentified
conditions. In an attempt to uncover these conditions, three experiments (N =
784) investigated the influence of unreinforced post-acquisition CS presentations
on EC effects resulting from simultaneous versus sequential pairings and pairings
with single versus multiple USs. For all four types of CS-US pairings, EC effects
on self-reported evaluations were reduced by unreinforced CS presentations, but
only when the CSs had been rated after the initial presentation of CS-US
pairings. EC effects on an evaluative priming measure remained unaffected by
unreinforced CS presentations regardless of whether the CSs had been rated after
acquisition. The results suggest that reduced EC effects resulting from
unreinforced CS presentations are due to judgement-related processes during the
verbal expression of CS evaluations rather than genuine changes in the underlying
evaluative representations.
PMID- 25131507
TI - Regulation of object recognition and object placement by ovarian sex steroid
hormones.
AB - The ovarian hormones 17beta-estradiol (E2) and progesterone (P4) are potent
modulators of hippocampal memory formation. Both hormones have been demonstrated
to enhance hippocampal memory by regulating the cellular and molecular mechanisms
thought to underlie memory formation. Behavioral neuroendocrinologists have
increasingly used the object recognition and object placement (object location)
tasks to investigate the role of E2 and P4 in regulating hippocampal memory
formation in rodents. These one-trial learning tasks are ideal for studying acute
effects of hormone treatments on different phases of memory because they can be
administered during acquisition (pre-training), consolidation (post-training), or
retrieval (pre-testing). This review synthesizes the rodent literature testing
the effects of E2 and P4 on object recognition (OR) and object placement (OP),
and the molecular mechanisms in the hippocampus supporting memory formation in
these tasks. Some general trends emerge from the data. Among gonadally intact
females, object memory tends to be best when E2 and P4 levels are elevated during
the estrous cycle, pregnancy, and in middle age. In ovariectomized females, E2
given before or immediately after testing generally enhances OR and OP in young
and middle-aged rats and mice, although effects are mixed in aged rodents.
Effects of E2 treatment on OR and OP memory consolidation can be mediated by both
classical estrogen receptors (ERalpha and ERbeta), and depend on glutamate
receptors (NMDA, mGluR1) and activation of numerous cell signaling cascades
(e.g., ERK, PI3K/Akt, mTOR) and epigenetic processes (e.g., histone acetylation,
DNA methylation). Acute P4 treatment given immediately after training also
enhances OR and OP in young and middle-aged ovariectomized females by activating
similar cell signaling pathways as E2 (e.g., ERK, mTOR). The few studies that
have administered both hormones in combination suggest that treatment can enhance
OR and OP, but that effects are highly dependent on factors such as dose and
timing of administration. In addition to providing more detail on these general
conclusions, this review will discuss directions for future avenues of research
into the hormonal regulation of object memory.
PMID- 25131517
TI - A review of the relationship between the needs of mothers who have hearing
impairment children and their state-trait anxiety levels.
AB - This descriptive research was carried out to identify the relationship between
the needs of those mothers who have hearing impairment children and their
state/trait anxiety levels. Significant positive relationships were found between
the mothers' state anxiety level and the overall FNS score, the subscales of Need
for Information, Help Explaining to Others, Community Services, Financial
Assistance and Family Functioning and also significant positive relationship were
found between the trait anxiety level and the overall FNS score, the subscales of
Need for Information, Need for Support, Help Explaining to Others Community
Services, Financial Assistance and Family Functioning.
PMID- 25131518
TI - Geography and the burden of care in pediatric cancers.
AB - BACKGROUND: Childhood cancers typically require rigorous treatment at specialized
centers in urban areas, which can create substantial challenges for families
residing in remote communities. We evaluated the impact of residence and travel
time on the burden of care for families of childhood cancer patients. PROCEDURE:
We conducted a cross-sectional, self-administered survey of 354 caregivers of
pediatric cancer patients at a children's hospital serving a seven state area.
Measures included the impact of cancer treatment on relocation, employment,
schooling, and finances. We evaluated these domains by rural/urban residence and
travel time (>1 hour and >2 hours) to the hospital in multivariable regression
models. RESULTS: Of the 29% of caregivers who reported moving residences as their
child was diagnosed, 33% reported that the move was due to their child's cancer.
Rural and remote (e.g., >1 hour travel time) caregivers missed more days of work
during the first month after diagnosis than did urban and local caregivers,
however, these differences did not persist over the first 6 months of therapy.
One-third of caregivers reported quitting or changing jobs as a direct result of
their child being diagnosed with cancer. Rural respondents had greater out-of
pocket travel expenses and reported a significantly greater perceived financial
burden. Rural patients missed more school days and were at an increased risk of
having to repeat a grade. CONCLUSIONS: Childhood cancer has an appreciable impact
on the lives of patients and caregivers. The burden is greater for those living
far from a treatment center.
PMID- 25131519
TI - Clinical and neuropsychological characteristics of euthymic bipolar patients
having a history of severe suicide attempt.
AB - OBJECTIVE: Identifying bipolar patients at high-suicide risk is a major health
issue. To improve their identification, we compared dimensional and
neuropsychological profile of bipolar patients with or without history of suicide
attempt, taking into account suicidal severity (i.e. admission to intensive
ward). METHOD: A total of 343 adult euthymic bipolar out-patients recruited in
the French FondaMental Advanced Centres of Expertise for Bipolar Disorder were
divided into three subgroups: 214 patients without history of suicide attempt, 88
patients with past history of non-severe suicide attempt and 41 patients with
past history of severe suicide attempt. General intellectual functioning, speed
of information processing, verbal learning and memory, verbal fluency and
executive functioning were assessed. RESULTS: Severe suicide attempters had lower
affective intensity and lability than non-severe attempters. Severe suicide
attempters outperformed non-severe attempters for verbal learning and non
attempters for Stroop word reading part after adjustment for study centre, age,
gender, educational level, antipsychotics use, depression score, anxious and
addictive comorbidities. CONCLUSION: Neuropsychological tasks commonly used to
assess bipolar patients do not seem accurate to identify suicide attempters in
euthymic patients. In the future, decision-making and emotional recognition tasks
should be assessed. Moreover, clinical and neuropsychological profiles should be
considered together to better define suicidal risk.
PMID- 25131521
TI - Fibroadenomatosis involving bilateral breasts and axillary accessory breast
tissues in a renal transplant recipient given cyclosporin A.
AB - We present the mammographic and sonographic findings in a case of
fibroadenomatosis involving both breasts and axillae in a renal transplant
patient after 16 years of treatment with cyclosporin A. Awareness of the fact
that cyclosporin A may induce the formation of fibroadenomas, including in
accessory breast tissue, is important for correct diagnosis and preventing
unnecessary intervention.
PMID- 25131520
TI - Correlation between congenital heart defects and maternal copper and zinc
concentrations.
AB - BACKGROUND: The aim of this study was to investigate the correlation between
maternal concentrations of copper and zinc and the risk of having an infant with
a congenital heart defect (CHD). METHODS: A multi-center hospital-based case
control study was conducted in China. A total of 212 cases and 212 controls were
recruited from pregnant women who received prenatal examinations in four tertiary
hospitals accredited to perform prenatal diagnosis in the cities of Shenzhen,
Zhenzhou, Fuzhou and Wuhan between February 2010 and November 2011. Correlation
between CHDs and maternal copper and zinc concentrations was estimated by a 1:1
conditional logistic regression. Also the interaction between copper and zinc was
analyzed. RESULTS: Compared with the controls, mothers with hair copper
concentrations of 17.77 MUg/g or more were more likely to have a child with a CHD
than those with a lower concentration. The adjusted odds ratio was 5.70 (95%
confidence interval, 2.58-12.61) for CHDs and 6.32 (95% confidence interval, 2.11
18.92) for conotruncal defects. Zinc concentrations were not significantly
different in the case and control groups. The results suggest that mothers whose
zinc content was 104.60 MUg/g or less did not have a significantly higher risk of
having a child with a CHD. No interaction between maternal copper and zinc
concentrations was observed in the multiplicative or additive model. CONCLUSION:
Women with excessive copper concentrations have a significantly increased risk of
having offspring with a CHD. A low maternal zinc status might have a correlation
with CHDs, and an interaction between copper and zinc might exists, but an
epidemiological study with a larger sample size is needed to confirm this
finding.
PMID- 25131523
TI - Usefulness of lewis lead for visualizing p-wave.
PMID- 25131522
TI - Novel tricyclic[2,1-f]theophylline derivatives of LCAP with activity in mouse
models of affective disorders.
AB - OBJECTIVES: The purpose of this study was to investigate the central activity of
the two new imidazo[2,1-f]purine-2,4-dione derivatives behaved as presynaptic
5HT1A receptor agonists and postsynaptic 5HT1A , 5HT2A and D2 receptors
antagonists. The compounds were examined using animal tests towards
antipsychotic, antidepressant- and anxiolytic-like properties and then compared
with effects evoked by an atypical antipsychotic drug ziprasidone. METHODS: D
amphetamine-induced hyperactivity test was used to determine antipsychotic-like
activity of compounds 7 and 9. The forced swim test (FST) and the four-plate test
were conducted to investigate antidepressant- and antianxiety-like activity,
respectively, of studied agents. The investigated compounds 7, 9 and ziprasidone
were administered intraperitoneally 60 min before the tests. Diazepam and
imipramine were used as standard anxiolytic and antidepressant drugs,
respectively. KEY FINDINGS: The obtained results demonstrate that new synthesized
compound 9 evokes antipsychotic-like activity alike ziprasidone and, in contrary
to the antipsychotic drug, shows antidepressant- and anxiolytic-like properties
in behavioural tests in mice. CONCLUSIONS: The present preclinical results
indicate that one of the two investigated imidazo[2,1-f]purine-2,4-dione
derivatives, compound 9, with methyl group at 7 position of imidazo[2,1-f]purine
2,4-dione fragment and the ortho-OCH3 substituent in the aryl moiety, acts as an
antipsychotic drug with additional antidepressant and anxiolytic properties.
PMID- 25131524
TI - Spontaneous coronary artery dissection.
AB - Spontaneous coronary artery dissection (SCAD) is a rare but challenging clinical
entity of unknown etiology. From a pathophysiological standpoint, SCAD may occur
in patients with a coronary intimal tear (presenting with the classic
angiographic "flap" and multiple lumens), but also in patients without an intimal
rupture (presenting as an intramural hematoma). Until now, available information
on SCAD was largely based on multiple, small case-series studies but, recently,
data from relatively large registries have cast a new light on this disease.
Classically, SCAD was thought to present in young females without traditional
atherosclerotic risk factors but recent reports suggest a broader clinical
spectrum encompassing older patients with associated coronary artery disease. In
this review, we concentrate on 3 main aspects of this unique disease: (1) the
value of intracoronary diagnostic techniques (intravascular ultrasound and
optical coherence tomography) to complement coronary angiography and to provide
novel diagnostic insights on this elusive clinical condition; (2) the growing
clinical evidence suggesting an association and potential causation between
fibromuscular dysplasia and SCAD; and (3) the challenges of coronary
revascularization in this adverse anatomic setting, together with recent data
suggesting that a initial, conservative medical management may be preferable for
the majority of patients with SCAD.
PMID- 25131525
TI - Diagnosis of Takotsubo cardiomyopathy.
AB - Takotsubo cardiomyopathy, also known as left ventricular apical ballooning
syndrome and stress-induced cardiomyopathy, is typically characterized by
transient systolic dysfunction of the apical and mid-segments of the left
ventricle, in the absence of obstructive coronary artery lesions. Patients may
present with symptoms and signs of acute coronary syndrome, and the provider is
challenged to differentiate between these conditions. In this review, we guide
the reader through the diagnostic pathway, focusing on differential diagnoses and
diagnostic criteria for takotsubo cardiomyopathy.
PMID- 25131526
TI - [Post-stroke depression].
AB - Cerebrovascular diseases are associated with a high incidence of psychiatric
disorders. Depressive illness after stroke has been extensively investigated
during the last three decades. Post-stroke depression is estimated to occur in 30
35% of the patients during the first year after stroke. Numerous studies have
given information on its prevalence, pathogenesis, clinical course, treatment and
prevention. Despite the high level of comorbidity, depressive symptoms appear to
remain frequently unrecognized and untreated. This has a negative effect on the
rehabilitation, quality of live, cognitive function and mortality of stroke
patients.
PMID- 25131527
TI - [Cardiovascular screening programme in the Central Hungarian region. The
Budakalasz Study].
AB - INTRODUCTION: The reduction in mortality due to prevention programmes observed in
some European countries is not currently reached in Hungary. Effective prevention
is based on the screening of risk factors and health state of the population.
AIM: The goal of this study was to develop a longitudinal, population-based
screening programme in the Central Hungarian region in order to collect
information on the health state and cardiovascular risk profile of the citizens
and discover new potential cardiovascular risk factors. METHOD: The Budakalasz
Study is a self-voluntary programme involving the adult population (>20 yrs,
approx. 8000 persons), and it consists of questionnaires, non-invasive tests
(anthropometry, cardiac echo, carotid duplex scan, blood pressure measurement,
ankle-brachial index), venous blood sample collection and laboratory tests.
RESULTS: Until January, 2014, 2420 persons (30% of the population, male: 41.2%,
average age 54.8 years) participated in the programme. Cardiovascular morbidity
was higher in contrast to a former national survey. The number of risk factors
and, therefore, 10-year cardiovascular risk were also elevated in this
population. CONCLUSIONS: These findings underline the importance of screening
programmes and effective therapies.
PMID- 25131528
TI - [International comparative study on health condition of young people].
AB - INTRODUCTION: The connection between physical condition, coping strategies and
emotional intelligence is widely studied in the international literature, but
comparative research data collected among Transylvanian and Hungarian adolescents
are not available in contemporary psychological literature. AIM: The aim of the
authors was to study health indicators, emotional intelligence and coping
strategies among adolescents and analyse connections between these factors and
physical condition as part of an international research. METHOD: The physical
condition, coping strategies and emotional intelligence of 390 individuals, aged
between 13 and 19 years living in Debrecen (Hungary) and Ermihalyfalva (Romania)
were observed. RESULTS: adaptive (i. e. problem-focused) coping strategies used
in stressful situations resulted in lower depression rates, as well as better
mental well-being than the maladaptive ones such as emotional clearing, self
punishment, distraction of attention. Adolescents showing higher emotional
intelligence had lower depression levels and better mental well-being.
CONCLUSIONS: Institutionally initiated emotional intelligence and coping strategy
development for young people may prove to be an important preventive
interventional public health programme. This may serve as a basis to assist
health-consciousness and personality formatting.
PMID- 25131529
TI - [Patient rights in the remote past? Regulation of medical services until the 19th
century, based particularly on Hungary's first comprehensive Royal Decree of the
health system].
PMID- 25131530
TI - [The place of our Earth in the cosmos and the turning points in its history-
thoughts related to climate change].
PMID- 25131533
TI - Acute fatal upper airway obstruction from an occult cavernous hemangioma of the
larynx.
AB - A 42-year-old previously well man collapsed while holding his throat.
Resuscitation was unsuccessful, and at autopsy, the most significant findings
were limited to the larynx, pharynx, and anterior mediastinum where there were
multinodular dark blue tumors. Within the larynx, the lower border of the tumor
was well demarcated, not extending beyond the vocal cords. A separate large
polypoidal tumor mass was attached to the right aryepiglottic fold by a thin
fibrous stalk. Histologic examination revealed numerous large, thin-walled
cavernous-type vascular spaces typical of a multifocal cavernous hemangioma.
Death was due to asphyxiation from obstruction of the upper airways by a
cavernous hemangioma of the larynx. Adult laryngeal hemangiomas are rare and are
usually supraglottic. This case demonstrates that pedunculated laryngeal
cavernous hemangiomas may remain occult until the initiation of an obstructive
episode with sudden collapse and death. In such instances, the diagnosis must
rely upon an autopsy examination.
PMID- 25131531
TI - alphabetaT cell receptors expressed by CD4(-)CD8alphabeta(-) intraepithelial T
cells drive their fate into a unique lineage with unusual MHC reactivities.
AB - Coreceptor CD4 and CD8alphabeta double-negative (DN) TCRalphabeta(+)
intraepithelial T cells, although numerous, have been greatly overlooked and
their contribution to the immune response is not known. Here we used T cell
receptor (TCR) sequencing of single cells combined with retrogenic expression of
TCRs to study the fate and the major histocompatibility complex (MHC) restriction
of DN TCRalphabeta(+) intraepithelial T cells. The data show that commitment of
thymic precursors to the DN TCRalphabeta(+) lineage is imprinted by their TCR
specificity. Moreover, the TCRs they express display a diverse and unusual
pattern of MHC restriction that is nonoverlapping with that of CD4(+) or
CD8alphabeta(+) T cells, indicating that they sense antigens that are not
recognized by the conventional T cell subsets. The new insights indicate that DN
TCRalphabeta(+) T cells form a third lineage of TCRalphabeta T lymphocytes
expressing a variable TCR repertoire, which serve nonredundant immune functions.
PMID- 25131532
TI - Elevated T cell receptor signaling identifies a thymic precursor to the
TCRalphabeta(+)CD4(-)CD8beta(-) intraepithelial lymphocyte lineage.
AB - The origin and developmental pathway of intestinal T cell receptor alphabeta(+)
CD4(-)CD8beta(-) intraepithelial lymphocytes (unconventional iIELs), a major
population of innate-like resident cytolytic T cells, have remained elusive. By
cloning and expressing several TCRs isolated from unconventional iIELs, we
identified immature CD4(lo)CD8(lo)(DP(lo))CD69(hi)PD-1(hi) thymocytes as the
earliest postsignaling precursors for these cells. Although these precursors
displayed multiple signs of elevated TCR signaling, a sizeable fraction of them
escaped deletion to selectively engage in unconventional iIEL differentiation.
Conversely, TCRs cloned from DP(lo)CD69(hi)PD-1(hi) thymocytes, a population
enriched in autoreactive thymocytes, selectively gave rise to unconventional
iIELs upon transgenic expression. Thus, the unconventional iIEL precursor
overlaps with the DP(lo) population undergoing negative selection, indicating
that, concomitant with the downregulation of both CD4 and CD8 coreceptors, a
balance between apoptosis and survival signals results in outcomes as divergent
as clonal deletion and differentiation to the unconventional iIEL lineage.
PMID- 25131534
TI - Risk of drug-induced liver injury from tumor necrosis factor antagonists.
AB - BACKGROUND & AIMS: Antagonists of tumor necrosis factor (anti-TNF agents) can
cause drug-induced liver injury (DILI), yet little is known about the level of
risk. METHODS: We identified cases of DILI caused by anti-TNF agents in Iceland,
from 2009 through 2013, at the National University Hospital of Iceland (n = 11).
We collected data on the total use of the drugs by patients with DILI, and
outcomes, compared with patients who received anti-TNF agents but who did not
develop DILI (controls, n = 22). RESULTS: Of the 11 cases of DILI identified (8
women; mean age, 46 y), 9 cases were caused by infliximab. DILI developed in 1 of
120 patients who received infliximab, 1 in 270 patients who received adalimumab,
and 1 in 430 patients who received etanercept. Most patients with infliximab
associated DILI developed this disorder after 4 infusions (n = 6). Four patients
had jaundice at diagnosis of DILI, and 8 patients had hepatocellular liver
injury. The mean peak level of alanine aminotransferase was 704 U/L, of aspartate
aminotransferase was 503 U/L, of alkaline phosphatase was 261 U/L, and of
bilirubin was 47 MUmol/L. Seven patients with DILI were tested for antinuclear
antibodies before therapy with an anti-TNF agent and 3 had positive test results,
compared with 5 of the 14 controls tested. At DILI diagnosis, 8 of 11 patients
tested positive for antinuclear antibodies. Of liver biopsy specimens collected
from 5 patients with DILI, 3 showed signs of severe acute hepatitis. Only 9% of
the patients who developed DILI received methotrexate during anti-TNF therapy,
compared with 59% of controls (P = .009). DILI was treated with steroids in 5
patients, and in 4 cases steroid therapy was discontinued without relapse. Eight
patients with DILI went on to receive treatment with different TNF antagonists
without developing DILI. CONCLUSIONS: Of anti-TNF agents, infliximab is
associated most frequently with DILI, developing in 1 of 120 patients who
received this drug. Fifty percent of patients with anti-TNF-associated DILI
required steroid therapy, but most did not need long-term treatment. The addition
of methotrexate to anti-TNF therapy might reduce the risk of DILI.
PMID- 25131535
TI - Structural and mutational studies on an aldo-keto reductase AKR5C3 from
Gluconobacter oxydans.
AB - An aldo-keto reductase AKR5C3 from Gluconobacter oxydans (designated as Gox0644)
is a useful enzyme with various substrates, including aldehydes, diacetyl, keto
esters, and alpha-ketocarbonyl compounds. The crystal structures of AKR5C3 in
apoform in complex with NADPH and the D53A mutant (AKR5C3(-D53A) ) in complex
with NADPH are presented herein. Structure comparison and site-directed
mutagenesis combined with biochemical kinetics analysis reveal that the conserved
Asp53 in the AKR5C3 catalytic tetrad has a crucial role in securing active pocket
conformation. The gain-of-function Asp53 to Ala mutation triggers conformational
changes on the Trp30 and Trp191 side chains, improving NADPH affinity to AKR5C3,
which helps increase catalytic efficiency. The highly conserved Trp30 and Trp191
residues interact with the nicotinamide moiety of NADPH and help form the NADPH
binding pocket. The AKR5C3(-W30A) and AKR5C3(-W191Y) mutants show decreased
activities, confirming that both residues facilitate catalysis. Residue Trp191 is
in the loop structure, and the AKR5C3(-W191Y) mutant does not react with
benzaldehyde, which might also determine substrate recognition. Arg192, which is
involved in the substrate binding, is another important residue. The introduction
of R192G increases substrate-binding affinity by improving hydrophobicity in the
substrate-binding pocket. These results not only supplement the AKRs superfamily
with crystal structures but also provide useful information for understanding the
catalytic properties of AKR5C3 and guiding further engineering of this enzyme.
PMID- 25131536
TI - Design, synthesis, in silico and in vitro studies of novel 4-methylthiazole-5
carboxylic acid derivatives as potent anti-cancer agents.
AB - Since inhibitors of mucin onco proteins are potential targets for breast cancer
therapy, a series of novel 4-methylthiazole-5-carboxylic acid (1) derivatives 3a
k were synthesized by the reaction of 1 with SOCl2 followed by different
bases/alcohols in the presence of triethylamine. Once synthesized and
characterized, their binding modes with MUC1 were studied by molecular docking
analysis using Aruglab 4.0.1 and QSAR properties were determined using HyperChem.
All synthesized compounds were screened for in vitro anti-breast cancer activity
against MDA-MB-231 breast adenocarcinoma cell lines by Trypan-blue cell viability
assay and MTT methods. Compounds 1, 3b, 3d, 3e, 3i and 3f showed good anti-breast
cancer activity. Since 1 and 3d exhibited high potent activity against MDA-MB-231
cell lines, they show could be effective mucin onco protein inhibitors.
PMID- 25131537
TI - Inhibition of activated STAT5 in Bcr/Abl expressing leukemia cells with new
pimozide derivatives.
AB - STATs are transcription factors acting as intracellular signaling after
stimulation with cytokines, growth factors and hormones. STAT5 is also
constitutively active in many forms of cancers, including chronic myelogenous
leukemia, acute lymphoblastic leukemia and Hodgkin's lymphoma. Recently,
literature reported that the neuroleptic drug pimozide inhibits STAT5
phosphorylation inducing apoptosis in CML cells. We undertook an investigation
from pimozide structure, obtaining simple derivatives with cytotoxic and STAT5
inhibitory activity, two of them markedly more potent than pimozide.
PMID- 25131538
TI - Screening and identification of novel compounds with potential anti-proliferative
effects on gallium-resistant lung cancer through an AXL kinase pathway.
AB - The clinical application of gallium compounds as anticancer agents is hampered by
development of resistance. As a potential strategy to overcome the limitation,
eight series of compounds were identified through virtual screening of AXL kinase
homology model. Anti-proliferative studies were carried using gallium-sensitive
(S) and gallium-resistant (R) human lung adenocarcinoma (A549) cells. Compounds
5476423 and 7919469 were identified as leads. The IC50 values from treating R
cells showed compounds 5476423 and 7919469 had 80 fold and 13 fold increased
potency, respectively, compared to gallium acetylacetonate (GaAcAc). The efficacy
of GaAcAc against R-cells was increased 2 fold and 1.2 fold when combined with
compounds 5476423 and 7919469, respectively. Compared with S-cells, R-cells
showed elevated expression of AXL protein, which was significantly suppressed
through treatments with the lead compounds. It is anticipated that the lead
compounds could be applied in virtual screening programs to identify novel
scaffolds for new therapeutic agents as well as combinatorial therapy agents in
gallium resistant lung cancer.
PMID- 25131539
TI - Synthesis, in vitro and in silico studies of a PPARgamma and GLUT-4 modulator
with hypoglycemic effect.
AB - Compound {4-[({4-[(Z)-(2,4-dioxo-1,3-thiazolidin-5
ylidene)methyl]phenoxy}acetyl)amino]phenoxy}acetic acid (1) was prepared and the
in vitro relative expression of PPARgamma, GLUT-4 and PPARalpha, was estimated.
Compound 1 showed an increase of 2-fold in the mRNA expression of PPARgamma
isoform, as well as the GLUT-4 levels. The antidiabetic activity of compound 1
was determined at 50 mg/Kg single dose using a non insulin dependent diabetes
mellitus (NIDDM) rat model. The in vivo results indicated a significant decrease
of plasma glucose levels, during the 7 h post-administration. Also, we performed
a molecular docking of compound 1 into the ligand binding pocket of PPARgamma,
showing important short contacts with residues Ser289, His323 and His449 in the
active site.
PMID- 25131540
TI - Correlates of quality of sexual life in male and female patients with Parkinson
disease and their partners.
AB - INTRODUCTION: Patients with Parkinson disease (PD) and their partners may
experience a worsening of their sexual life. AIM: To assess quality of sexual
life (QoSL) in male and female PD patients and their partners. MATERIALS AND
METHODS: Medical, demographic and clinical data was collected regarding
consecutive PD patients, including depression, and motor symptom rating.
Partners' data included the short form-12 health questionnaire (SF-12). All
patients and partners filled the 5-item QoSL questionnaire. RESULTS: Data from 89
PD patients (66 men) and 69 spouses (52 women) was analyzed. Male patients
rejected sex significantly less than female patients and their sexual desire was
higher, but female patients reported higher sexual satisfaction. Patients and
partners similarly perceived their relationship which was averagely good.
Analysis within couples demonstrated that better QoSL of patients could be
predicted by gender (male), better QoSL of their partners and, motor severity,
but not the patient's depression, age or use of l-dopa. The partner's QoSL was
explained by younger age, and better motor scores of their parkinsonian partner.
Treatment of the PD patient with l-dopa or dopamine agonist was associated with
worse partner's QoSL. CONCLUSION: Differences in QoSL of male and female PD
patients and within couples were found. These findings suggest that focusing on
partner's needs may improve QoSL of patients and partners troubled by PD.
PMID- 25131542
TI - Transgenerational epigenetics and brain disorders.
AB - Neurobehavioral and psychiatric disorders are complex diseases with a strong
heritable component; however, to date, genome-wide association studies failed to
identify the genetic loci involved in the etiology of these brain disorders.
Recently, transgenerational epigenetic inheritance has emerged as an important
factor playing a pivotal role in the inheritance of brain disorders. This field
of research provides evidence that environmentally induced epigenetic changes in
the germline during embryonic development can be transmitted for multiple
generations and may contribute to the etiology of brain disease heritability. In
this review, we discuss some of the most recent findings on transgenerational
epigenetic inheritance. We particularly discuss the findings on the epigenetic
mechanisms involved in the heritability of alcohol-induced neurobehavioral
disorders such as fetal alcohol spectrum disorders.
PMID- 25131544
TI - Epigenetic regulatory mechanisms in stress-induced behavior.
AB - Stress response is considered to have adaptive value for organisms faced with
stressful condition. Chronic stress however adversely affects the physiology and
may lead to neuropsychiatric disorders. Repeated stressful events in animal
models have been shown to cause long-lasting changes in neural circuitries at
molecular, cellular, and physiological level, leading to disorders of mood as
well as cognition. Molecular studies in recent years have implicated diverse
epigenetic mechanisms, including histone modifications, DNA methylation, and
noncoding RNAs, that underlie dysregulation of genes in the affected neural
circuitries in chronic stress-induced pathophysiology. A review of the myriad
epigenetic regulatory mechanisms associated with neural and behavioral responses
in animal models of stress-induced neuropsychiatric disorders is presented here.
The review also deals with clinical evidence of the epigenetic dysregulation of
genes in psychiatric disorders where chronic stress appears to underlie the
etiopathology.
PMID- 25131545
TI - Epigenetics of schizophrenia: an open and shut case.
AB - During the last decade and a half, there has been an explosion of data regarding
epigenetic changes in schizophrenia. Most initial studies have suggested that
schizophrenia is characterized by an overly restrictive chromatin state based on
increases in transcription silencing histone modifications and DNA methylation at
schizophrenia candidate gene promoters and increases in the expression of enzymes
that catalyze their formation. However, recent studies indicate that the
pathology is more complex. This complexity may greatly impact pharmacological
approaches directed at targeting epigenetic abnormalities in schizophrenia. The
current review explores epigenetic studies of schizophrenia and what this can
tell us about the underlying pathophysiology. We hypothesize based on recent
studies that it is also plausible that drugs that further restrict chromatin may
be efficacious.
PMID- 25131546
TI - Epigenetic mechanisms in autism spectrum disorder.
AB - Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by
impaired social interactions, language deficits, as well as restrictive or
repetitive behaviors. ASD is clinically heterogeneous with a complex
etiopathogenesis which may be conceptualized as a dynamic interplay between
heterogeneous environmental cues and predisposing genetic factors involving
complex epigenetic mechanisms. Inherited and de novo copy number variants provide
novel information regarding genes contributing to ASD. Epigenetic marks are
stable, yet potentially reversible, chromatin modifications that alter gene
expression profiles by locally changing the degree of nucleosomal compaction,
thereby opening or closing promoter access to the transcriptional machinery.
Here, we review progress on studies designed to provide a better understanding of
how epigenetic mechanisms impact transcriptional programs operative in the brain
that contribute to ASD.
PMID- 25131547
TI - MicroRNAs and ethanol toxicity.
AB - MicroRNAs (miRNAs) are a class of small nonprotein-coding RNAs (ncRNAs) that have
been shown to promote the degradation of target messenger RNAs and inhibit the
translation of networks of protein-coding genes to control the development of
cells and tissues, and facilitate their adaptation to environmental forces. In
this chapter, we will discuss recent data that show that miRNAs are an important
component of the epigenetic landscape that regulates the transcription as well as
the translation of protein-coding gene networks. We will discuss the evidence
that implicates miRNAs in both developmental and adult effects of alcohol
consumption. Understanding the interactions of this novel class of ncRNAs with
the epigenome will be important for understanding the etiology of alcohol
teratology and addiction as well as potential new treatment strategies.
PMID- 25131548
TI - Preface. Epigenetics.
PMID- 25131549
TI - A new way forward: improving maternal and child health in America.
PMID- 25131541
TI - Environmental alterations of epigenetics prior to the birth.
AB - The etiology of many brain diseases remains allusive to date after intensive
investigation of genomic background and symptomatology from the day of birth.
Emerging evidences indicate that a third factor, epigenetics prior to the birth,
can exert profound influence on the development and functioning of the brain and
over many neurodevelopmental syndromes. This chapter reviews how aversive
environmental exposure to parents might predispose or increase vulnerability of
offspring to neurodevelopmental deficit through alteration of epigenetics. These
epigenetic altering environmental factors will be discussed in the category of
addictive agents, nutrition or diet, prescriptive medicine, environmental
pollutant, and stress. Epigenetic alterations induced by these aversive
environmental factors cover all aspects of epigenetics including DNA methylation,
histone modification, noncoding RNA, and chromatin modification. Next, the
mechanisms how these environmental inputs influence epigenetics will be
discussed. Finally, how environmentally altered epigenetic marks affect
neurodevelopment is exemplified by the alcohol-induced fetal alcohol syndrome. It
is hoped that a thorough understanding of the nature of prenatal epigenetic
inputs will enable researchers with a clear vision to better unravel
neurodevelopmental deficit, late-onset neuropsychiatric diseases, or
idiosyncratic mental disorders.
PMID- 25131550
TI - Magnet application in ICD patients.
PMID- 25131551
TI - Smart vesicle kit for in situ monitoring of intracellular telomerase activity
using a telomerase-responsive probe.
AB - A smart vesicle kit was designed for in situ imaging and detection of cytoplasmic
telomerase activity. The vesicle kit contained a telomerase primer (TSP) and a
Cy5-tagged molecular beacon (MB) functionalized gold nanoparticle probe, which
were encapsulated in liposome for intracellular delivery. After the vesicle kit
was transfected into cytoplasm, the released TSP could be extended in the
presence of telomerase to produce a telomeric repeated sequence at the 3' end,
which was just complementary with the loop of MB assembled on probe surface.
Thus, the MB was opened upon hybridization to switch the fluorescent state from
"off" to "on". The fluorescence signal depended on telomerase activity, leading
to a novel strategy for in situ imaging and quantitative detection of the
cytoplasmic telomerase activity. The cytoplasmic telomerase activity was
estimated to be 3.2 * 10(-11), 2.4 * 10(-11), and 8.6 * 10(-13) IU in each HeLa,
BEL tumor and QSG normal cell, respectively, demonstrating the capability of this
approach to distinguish tumor from normal cells. The proposed method could be
employed for dynamic monitoring of the cytoplasmic telomerase activity in
response to a telomerase-based drug, suggesting the potential application in
discovery and screening of telomerase-targeted anticancer drugs.
PMID- 25131552
TI - The object of sexual desire: examining the "what" in "what do you desire?".
AB - INTRODUCTION: Over the past two decades, sexual desire and desire discrepancy
have become more frequently studied as have potential pharmaceutical
interventions to treat low sexual desire. However, the complexities of sexual
desire-including what exactly is desired-remain poorly understood. AIMS: To
understand the object of men's and women's sexual desire, evaluate gender
differences and similarities in the object of desire, and examine the impact of
object of desire discrepancies on overall desire for partner in men and women in
the context of long-term relationships. METHODS: A total of 406 individuals, 203
men and 203 women in a relationship with one another, completed an online survey
on sexual desire. MAIN OUTCOME MEASURES: Reports of the object of sexual desire
in addition to measures of sexual desire for current partner were collected from
both members of the couple. RESULTS: There were significant gender differences in
the object of sexual desire. Men were significantly more likely to endorse desire
for sexual release, orgasm, and pleasing their partner than were women. Women
were significantly more likely to endorse desire for intimacy, emotional
closeness, love, and feeling sexually desirable than men. Discrepancies within
the couple with regard to object of desire were related to their level of sexual
desire for partner, accounting for 17% of variance in men's desire and 37% of
variance in women's desire. CONCLUSIONS: This research provides insights into the
conceptualization of sexual desire in long-term relationships and the
multifaceted nature of sexual desire that may aid in more focused ways to
maintain desire over long-term relationships. Future research on the utility of
this perspective of sexual desire and implications for clinicians working with
couples struggling with low sexual desire in their relationships is discussed.
PMID- 25131543
TI - The epigenetic landscape of alcoholism.
AB - Alcoholism is a complex psychiatric disorder that has a multifactorial etiology.
Epigenetic mechanisms are uniquely capable of accounting for the multifactorial
nature of the disease in that they are highly stable and are affected by
environmental factors, including alcohol itself. Chromatin remodeling causes
changes in gene expression in specific brain regions contributing to the
endophenotypes of alcoholism such as tolerance and dependence. The epigenetic
mechanisms that regulate changes in gene expression observed in addictive
behaviors respond not only to alcohol exposure but also to comorbid
psychopathology such as the presence of anxiety and stress. This review
summarizes recent developments in epigenetic research that may play a role in
alcoholism. We propose that pharmacologically manipulating epigenetic targets, as
demonstrated in various preclinical models, hold great therapeutic potential in
the treatment and prevention of alcoholism.
PMID- 25131553
TI - A pathogenicity determinant maps to the N-terminal coat protein region of the
Pepino mosaic virus genome.
AB - Pepino mosaic virus (PepMV) poses a worldwide threat to the tomato industry.
Considerable differences at the genetic level allow for the distinction of four
main genotypic clusters; however, the basis of the phenotypic outcome is
difficult to elucidate. This work reports the generation of wild-type PepMV
infectious clones of both EU (mild) and CH2 (aggressive) genotypes, from which
chimeric infectious clones were created. Phenotypic analysis in three solanaceous
hosts, Nicotiana benthamiana, Datura stramonium and Solanum lycopersicum,
indicated that a PepMV pathogenicity determinant mapped to the 3'-terminal region
of the genome. Increased aggression was only observed in N. benthamiana, showing
that this factor is host specific. The determinant was localized to amino acids
11-26 of the N-terminal coat protein (CP) region; this is the first report of
this region functioning as a virulence factor in PepMV.
PMID- 25131554
TI - Pregnancy outcome according to male diagnosis after ICSI with non-ejaculated
sperm compared with ejaculated sperm controls.
AB - The aim of this study was to describe pregnancy outcome in couples who had
undergone ICSI using non-ejaculated sperm from men with non-obstructive
azoospermia, obstructive azoospermia and aspermia compared with the outcome of
ICSI with ejaculated sperm from men with severe oligozoospermia, treated during
the same time period. This nationwide cohort study included all children born
after ICSI with non-ejaculated sperm in Norway, from when the method was first
permitted in Norway in April 2004 to the end of 2010, resulting in 420
pregnancies and a total of 359 children. In 235 of these children, the father was
diagnosed with obstructive azoospermia, in 72 with non-obstructive azoospermia,
in 31 with aspermia, and in 21 the male cause was unclassifiable. The control
group consisted of 760 children from 939 pregnancies conceived by ICSI with
ejaculated sperm. Sex ratio, birth weight, rate of pregnancy loss and congenital
malformations were not significantly associated with sperm origin or the cause of
male factor infertility.
PMID- 25131555
TI - The long-term experiences of surrogates: relationships and contact with surrogacy
families in genetic and gestational surrogacy arrangements.
AB - This study examined the contact arrangements and relationships between surrogates
and surrogacy families and whether these outcomes differed according to the type
of surrogacy undertaken. Surrogates' motivations for carrying out multiple
surrogacy arrangements were also examined, and surrogates' psychological health
was assessed. Semi-structured interviews were administered to 34 women who had
given birth to a child conceived through surrogacy approximately 7 years prior to
interview. Some surrogates had carried out multiple surrogacy arrangements, and
data were collected on the frequency, type of contact, and surrogate's feelings
about the level of contact in each surrogacy arrangement, the surrogate's
relationship with each child and parent, and her experience of, and motivation
for, each surrogacy. Questionnaire measures of psychological health were
administered. Surrogates had completed a total of 102 surrogacy arrangements and
remained in contact with the majority of families, and reported positive
relationships in most cases. Surrogates were happy with their level of contact in
the majority of arrangements and most were viewed as positive experiences. Few
differences were found according to surrogacy type. The primary motivation given
for multiple surrogacy arrangements was to help couples have a sibling for an
existing child. Most surrogates showed no psychological health problems at the
time of data collection.
PMID- 25131556
TI - Androgen receptor CAG repeat length is associated with ovarian reserve but not
with ovarian response.
AB - The human androgen receptor (AR) gene contains a highly polymorphic CAG repeat
sequence within exon 1. In-vitro studies have shown a relationship between CAG
repeats in the AR gene and its transactivation potential. This variation in
length may play a role in anovulatory infertility. The objective of this study
was to investigate whether CAG polymorphism of the AR gene has a predictive value
for ovarian reserve, response and cycle outcome in an egg donor programme. CAG
length of the AR gene was determined in 147 oocyte donors. All donors underwent
ovarian stimulation with a gonadotrophin-releasing hormone antagonist protocol (n
= 355). No differences were reported in days of stimulation, gonadotrophin doses,
and number of oocytes retrieved. Clinical outcomes were not affected by the CAG
repeat length of the AR gene; the primary end-point, antral follicle count, was
significantly affected (P < 0.05). In conclusion, in a population of fertile egg
donors AR gene CAG polymorphism does not affect ovarian response to
gonadotrophins. Antral follicle count was associated with the CAG polymorphism
genotype. This suggests that genetic factors may increase susceptibility to poor
ovarian reserve, and that AR gene genotype could play a role in the natural
ovarian ageing process.
PMID- 25131557
TI - Effect of chromosomal polymorphisms of different genders on fertilization rate of
fresh IVF-ICSI embryo transfer cycles.
AB - To explore whether chromosomal polymorphisms of different genders affect outcomes
of fresh IVF and intracytoplasmic sperm injection (ICSI) embryo transfer cycles
differently, 37 couples with chromosomal polymorphisms were identified out of 614
infertile couples undergoing IVF-ICSI treatments. Group 1 included 20 couples in
which only the male carried chromosomal polymorphisms; group 2 included 17
couples with female carriers only; group 3 included 19 infertile couples with
normal karyotypes randomly selected as controls. A significantly lower
fertilization rate was found in group 1 compared with groups 2 and 3 (56.68% in
Group 1, 78.02% in group 2 and 71.74% in group 3; group 1 versus group 2, P <
0.001; group 1 versus group 3, P = 0.001; respectively). When stratified
according to fertilization method, the fertilization rate in IVF cycles of group
1 was significantly lower than group 3 (50.00% in Group 1, 73.89% in Group 3, P <
0.001). Fertilization rates in ICSI cycles between groups 1 and 3 were not
significantly different. This study suggests that male chromosomal polymorphisms
adversely influence fertilization rates of IVF cycles. The use of ICSI may
improve the success of infertility treatment by increasing the fertilization rate
for men with chromosomal polymorphisms.
PMID- 25131558
TI - In-vitro culture system for mesenchymal progenitor cells derived from waste human
ovarian follicular fluid.
AB - To characterize different cell populations in the human ovary, morphological and
functional characteristics of cell populations collected during routine IVF
procedures were studied. Cells obtained from follicular fluid grew in vitro under
minimal medium conditions, without growth factor, including leukaemia-inhibiting
factor. Morphological analysis revealed a heterogeneous cell population, with
cells displaying a fibroblast-like, epithelial-like and also neuron-like
features. Morpho-functional characteristics of fibroblast-like cells were similar
to mesenchymal stem cells, and, in particular, were positive for mesenchymal
stemness markers, including CD90, CD44, CD105, CD73, but negative for epithelial
proteins, such as cytokeratins, CD34 and CD45 antigens. Cell proliferation
activity at different times and colony-forming unit capability were evaluated,
and multipotency of a subset of granulosa cells was established by in-vitro
differentiation studies (e.g. osteogenic, chondrogenic and adipogenic
differentiation). This study suggests that cells provided by mesenchymal
plasticity can be easily isolated by waste follicular fluid, avoiding scraping of
human ovaries, and cultivated in minimal conditions. Successful growth of such
progenitor cells on three-dimensional cryogel scaffold provides the basis for
future developments in tissue engineering. This culture system may be regarded as
an experimental model in which biological behaviour is not influenced by specific
growth factors.
PMID- 25131559
TI - Quadrivalent asymmetry in reciprocal translocation carriers predicts meiotic
segregation patterns in cleavage stage embryos.
AB - The effect of quadrivalent geometry on meiotic behaviour was evaluated.
Segregation patterns of 404 cleavage stage embryos from 40 reciprocal
translocation carriers undergoing 75 PGD cycles were analysed according to the
asymmetric degree of quadrivalent. The percentage of alternate products with
severe asymmetric quadrivalents was significantly lower than patients with mild
asymmetric quadrivalents (22.5% versus 38.7%, P = 0.001). The incidence of 3:1
products was significantly higher in patients with severe compared with mild
asymmetric quadrivalents (23.1% versus 12.2%, P = 0.004). The incidence of
adjacent 1 (25.8% versus 24.3%), 2 (11.5% versus 12.6%) and 4:0/other segregation
products (17.0% versus 12.2%) were not statistically significantly different
between embryos from patients with severe or mild asymmetric quadrivalents. After
adjusting for the confounder of sex using a logistic regression model, the odds
of alternate embryos is about one-half for carriers classified as severe (OR
0.456, 95% CI 0.291 to 0.705), and the odds of 3:1 embryos is 2.2 times higher
for carriers with severe asymmetric quadrivalents (OR 2.235, 95% CI 1.318 to
3.846). Our results suggest that the meiotic segregation pattern is related to
the degree of asymmetry of specific quadrivalents. Severe asymmetric
quadrivalents increases the risk of abnormal embryos.
PMID- 25131560
TI - Association of serum uric acid levels to inflammation biomarkers and endothelial
dysfunction in obese prepubertal children.
AB - BACKGROUND: High serum uric acid (SUA) levels are present in patients with
metabolic syndrome (MetS), when the latter is associated with endothelial
dysfunction, inflammation, and hypertension. This increase in SUA levels may have
a key role in cardiovascular diseases. OBJECTIVE: We aim to quantify the
differences in inflammation biomarkers, endothelial dysfunction, and parameters
associated with MetS in obese prepubertal children compared to non-obese
children, and determine if there is a relationship between uric acid levels and
these variables. METHODS: A cross-sectional study was carried out on obese
children (6-9 yr old). The study included 43 obese children and the same number
of non-obese children (control group), matched by age and sex. SUA, C-reactive
protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1
(sICAM-1), glucose, insulin, lipid profile, and blood pressure were all measured.
RESULTS: SUA levels, CRP, and sICAM-1 were significantly higher in obese
children. In the obese group, SUA levels showed a positive correlation with body
mass index (BMI), insulin, homeostasis model assessment for insulin resistance
(HOMA-IR), CRP, IL-6, sICAM-1, and triglycerides (TGs), and correlated negatively
with high-density lipoprotein cholesterol (HDL-C) and Apo-AI, but not with Apo-B.
When adjusted for age, sex, and creatinine, it was noted that SUA levels are
independent predictive factors for sICAM-1, CRP, and IL-6. CONCLUSIONS:
Inflammation biomarkers, endothelial dysfunction, and parameters associated with
MetS are elevated in obese prepubertal children and correlate to uric acid
levels.
PMID- 25131561
TI - Ex vivo-expanded natural killer cells kill cancer cells more effectively than ex
vivo-expanded gammadelta T cells or alphabeta T cells.
AB - Adoptive immunotherapy of cancer is evolving with the development of novel
technologies for generating a large number of activated killer cells such as
natural killer (NK) cells, gammadelta T cells, and alphabeta T cells. We have
recently established large-scale culture methods to generate activated NK cells
from human peripheral blood, and demonstrated that expanded NK cells have higher
cytotoxicity against cancer cells than freshly isolated NK cells. In this study,
we compared cultured NK cells with cultured gammadelta T and alphabeta T cells
that were prepared by conventional culture methods regarding the expression of
cytotoxic molecules and cytotoxicity against cancer cells. Natural cytotoxicity
receptors such as NKp30, NKp44 and NKp46, and perforin were expressed most
exclusively on NK cells. Granzyme A, NKG2D, and interferon-gamma were dominantly
expressed in NK cells and gammadelta T cells but not in alphabeta T cells.
Consistent with the expression profiles of the cytotoxic molecules, cultured NK
cells from both healthy volunteers and cancer patients demonstrated significantly
higher cytotoxicity against cancer cell lines, including MHC class I-positive
cell lines, compared with cultured gammadelta T cells and cultured alphabeta T
cells. Additionally, NK cells, unlike gammadelta T cells or alphabeta T cells,
expressed high levels of CD16, and showed augmented cytotoxicity when co
administered with an anti-CD20 monoclonal antibody drug, rituximab. These results
suggest the excellent efficacy of expanded NK cells for cancer treatment.
PMID- 25131563
TI - Commercial sexual exploitation and sex trafficking of children in the United
States.
AB - Child commercial sexual exploitation and sex trafficking are global health
problems requiring a multidisciplinary approach by individuals, organizations,
communities, and national governments. The adverse emotional, physical, and
social consequences for victims are legion and in many areas of the United States
and the rest of the world, victim resources are scarce. Since violence,
deprivation, abuse, and infection are so integral to the exploitation experience,
victims may present for care to community and academic pediatric and adolescent
health care providers. It is essential that medical professionals have the
knowledge, skills, and resources to recognize victims, assess their needs, and
treat them appropriately, including making key referrals for community services.
However, to date medical information and resources regarding commercial sexual
exploitation and sex trafficking has been sparse. There are no clinically
validated screening tools specifically designed to identify victims in the health
care setting and since victims seldom self-identify, it is likely that the
majority of victims are unrecognized. The opportunity for comprehensive
assessment and intervention is lost. Further, professionals receive little
training on appropriate interview techniques for this special population, and
many are ill equipped to ensure safety and optimal medical evaluation during the
visit. This article provides a general overview of child sex trafficking and
commercial sexual exploitation (CSEC), describing the epidemiology of
international and domestic exploitation, and reviewing the challenges of
conducting research on this population. The five stages of trafficking are
explained, as are typical physical and emotional consequences of exploitation.
The medical evaluation is described, including potential indicators of CSEC and
sex trafficking, common medical presentations by victims, approaches to the
comprehensive medical interview, and the appropriate medical exam with diagnostic
testing and treatment. Finally, a discussion of common victim needs is provided,
with a description of resources and referrals.
PMID- 25131564
TI - Environmental contributors to autism: the pediatrician's role.
PMID- 25131565
TI - Commentary: Commercial sexual exploitation--a survivor's perspective: "Can you
help me? Do you care?".
PMID- 25131562
TI - Cannabinoid modulation of alpha2 adrenergic receptor function in rodent medial
prefrontal cortex.
AB - Endocannabinoids acting at the cannabinoid type 1 receptor (CB1R) are known to
regulate attention, cognition and mood. Previous studies have shown that, in the
rat medial prefrontal cortex (mPFC), CB1R agonists increase norepinephrine
release, an effect that may be attributed, in part, to CB1Rs localised to
noradrenergic axon terminals. The present study was aimed at further
characterising functional interactions between CB1R and adrenergic receptor (AR)
systems in the mPFC using in vitro intracellular electrophysiology and high
resolution neuroanatomical techniques. Whole-cell patch-clamp recordings of layer
V/VI cortical pyramidal neurons in rats revealed that both acute and chronic
treatment with the synthetic CB1R agonist WIN 55,212-2 blocked elevations in
cortical pyramidal cell excitability and increases in input resistance evoked by
the alpha2-adrenergic receptor (alpha2-AR) agonist clonidine, suggesting a
desensitisation of alpha2-ARs. These CB1R-alpha2-AR interactions were further
shown to be both action potential- and gamma-aminobutyric acid-independent. To
better define sites of cannabinoid-AR interactions, we localised alpha2A
adrenergic receptors (alpha2A-ARs) in a genetically modified mouse that expressed
a hemoagglutinin (HA) tag downstream of the alpha2A-AR promoter. Light and
electron microscopy indicated that HA-alpha2A-AR was distributed in axon
terminals and somatodendritic processes especially in layer V of the mPFC. Triple
labeling immunocytochemistry revealed that alpha2A-AR and CB1R were localised to
processes that contained dopamine-beta-hydroxylase, a marker of norepinephrine.
Furthermore, HA-alpha2A-AR was localised to processes that were directly apposed
to CB1R. These findings suggest multiple sites of interaction between cortical
cannabinoid-adrenergic systems that may contribute to understanding the effect of
cannabinoids on executive functions and mood.
PMID- 25131566
TI - Quality of life in caregivers of severely disabled war survivors.
AB - PURPOSE: To evaluate quality of life (QOL) of caregivers of severely disabled war
survivors and identify variables threatening caregivers' QOL. METHODS: A cross
sectional study was performed on 532 caregivers of Iran-Iraq war related injured
survivors by using Persian version of 36-item Short Form Health Survey (SF-36).
FINDINGS: Caregivers had lower QOL compared to the Iranian female population (p <
.001). Caregivers of amputees had better SF-36 scores compared to caregivers of
two groups of chemical warfare survivors (p ranging from .01 to <.001).
Caregiving to chemical warfare and being married at the time of trauma were the
independent predictors of poor QOL in both the physical component summary (OR =
5.08, 95% CI = 3.35-7.7; OR = 0.57, 95% CI = 0.37-0.89) and the mental component
summary (OR = 4.12, 95% CI = 2.68-6.32; OR = 0.63, 95% CI = 0.40-0.98).
CONCLUSION AND CLINICAL RELEVANCE: Caregivers of war veterans suffer from poor
QOL. Chemical warfare agents contribute to more persistent poor QOL in caregivers
than the injuries caused by conventional weapons.
PMID- 25131567
TI - Prehypertension in rural northeastern China: results from the northeast China
rural cardiovascular health study.
AB - This study aimed to determine the present status of prehypertension in rural
China. It was conducted between January and August 2013, using a multistage
clustering method to select a representative sample of individuals (>=35 years
old), resulting in a study population of 11,576 adults. Prehypertension was
defined as a systolic blood pressure (BP) in the range of 120 mm Hg to 139 mm Hg
and/or a diastolic BP between 80 mm Hg and 89 mm Hg according to the Seventh
Report of the Joint National Committee on the Prevention, Detection, Evaluation,
and Treatment of High Blood Pressure (JNC 7). The results showed that the mean+/
standard deviation systolic and diastolic BP values for the entire population
were 141.8+/-23.5 mm Hg and 82.1+/-11.8 mm Hg, respectively. Among the whole
population, 35.1% of men and 32.5% of women were prehypertensive. Multiple
logistic regression analysis showed that high body mass index, advanced age,
alcohol consumption, diabetes, high triglyceride and low-density lipoprotein
cholesterol levels, and elevated diet score were risk factors for
prehypertension. This study indicates that there is a high prevalence of
prehypertension in rural China and confirms the importance of healthy lifestyles-
including the control of obesity, diabetes, and dyslipidemia--to decrease the
incidence of prehypertension.
PMID- 25131569
TI - Negative poisson's ratio in single-layer black phosphorus.
AB - The Poisson's ratio is a fundamental mechanical property that relates the
resulting lateral strain to applied axial strain. Although this value can
theoretically be negative, it is positive for nearly all materials, though
negative values have been observed in so-called auxetic structures. However,
nearly all auxetic materials are bulk materials whose microstructure has been
specifically engineered to generate a negative Poisson's ratio. Here we report
using first-principles calculations the existence of a negative Poisson's ratio
in a single-layer, two-dimensional material, black phosphorus. In contrast to
engineered bulk auxetics, this behaviour is intrinsic for single-layer black
phosphorus, and originates from its puckered structure, where the pucker can be
regarded as a re-entrant structure that is comprised of two coupled orthogonal
hinges. As a result of this atomic structure, a negative Poisson's ratio is
observed in the out-of-plane direction under uniaxial deformation in the
direction parallel to the pucker.
PMID- 25131568
TI - First description of scrotal testicles in a dog affected by 78, XX testicular
disorder of sex development.
AB - An eight-month-old female dog presented with ambiguous external genitalia. A
thorough clinical examination together with various imaging techniques and a
histology examination showed the presence of two testicles linked to both the
Mullerian and Wolffian ducts. The discovery of the 78,XX SRY-negative karyotype
led to the diagnosis of incoherence between the chromosomal and gonadal sex,
which is typical for a 78,XX testicular disorder of sex development. Our case was
unique because the testicles were still located in their normal scrotal position,
whereas the literature contains reports of the presence of cryptorchid testicles
in this karyotype setting. To our knowledge, this is the first case that
describes an SRY-negative 78,XX testicular disorder of sex development with
bilateral scrotal testicles.
PMID- 25131570
TI - Overview of hepatitis B prevalence, prevention, and management in the Pacific
Islands and Territories.
AB - There are over 500-750 000 deaths per year because of hepatitis B virus (HBV)
related cirrhosis and liver cancer worldwide and the World Health Organization
Western Pacific Region has some of the highest endemic levels of HBV in the
world, particularly within China, South East Asia and Pacific Island Countries
and Territories (PICT). The PICT have unique ethnic diversity and a very high
prevalence of smoking and metabolic syndrome, both important risk factors for
liver fibrosis and liver cancer. However, in contrast to many Asian countries,
there is little published data on HBV prevalence and related liver disease burden
in PICT. In this review, the available published literature and World Health
Organization data for HBV prevalence and related liver disease and liver cancer
burden in PICT is outlined, and unmet needs for improving HBV prevention and
control in the region are highlighted.
PMID- 25131571
TI - Non-small cell lung cancer metastasis to the oral cavity: a case report.
AB - Lung cancer, including non-small cell lung cancer, remains prevalent in Australia
and has a very poor survival rate. Metastases to the oral cavity are a rare
occurrence that can arise from lung cancers. This case report describes the
presentation of a metastatic lesion from a poorly differentiated lung
adenocarcinoma on the mandibular buccal alveolar attached gingivae. The inpatient
had terminal disease with known pleural, brain and liver metastases and was
receiving palliative care at the time of diagnosis of the oral lesion.
PMID- 25131580
TI - Enhanced RBC Aggregation in Type 2 Diabetes Patients.
AB - BACKGROUND: This study aimed to investigate the relationship between HbA1c and
RBC aggregation in type 2 diabetes mellitus (T2DM) patients by analysis of data
from routine clinical tests and from in vitro experiments. METHODS: A total of
2,111 inpatients with type 2 diabetes were selected and among them, 364 patients
(Group A) had limited influence of plasma proteins on erythrocyte sedimentation
rate (ESR) and was compared with the rest of the 1,747 inpatients (Group B). ESR,
HbA1c , WBC, CRP, Fbg, and HCT were measured in all samples. Sixty samples were
also collected from T2DM patients and used for in vitro ESR studies. Spearman's
correlation coefficients were employed to reflect the correlation between ESR and
other parameters. Mann-Whitney U test was used to compare the study parameters.
RESULTS: The test results for Group A were lower than Group B with respect to
ESR, age, HCT, HbA1c , CRP, WBC, and Fbg. Only the difference in HbA1c , CRP, and
Fbg values had statistical significance (P < 0.05). In addition, HbA1c correlated
better with ESR for Group A (R = 0.622) than Group B (R = 0.563), whereas CRP and
Fbg were contrary to this. In the in vitro studies, the HbA1c values were
classified into the subgroups of 6.5-8.0%, 8.1-10%, and >10%. The corresponding
ESR values were 28 +/- 5.1 mm/h, 33 +/- 2.7 mm/h, and 40 +/- 4.1 mm/h,
respectively. CONCLUSION: ESR results of T2DM patients were elevated that was
mainly caused by Fbg levels, and in addition HbA1c in part contributed to RBC
aggregation.
PMID- 25131581
TI - Extensive structural rearrangements upon reduction of 9H-9-borafluorene.
AB - Common wisdom has it that organoboranes are readily oxidized. Described herein is
that also their reduction can result in remarkable chemistry. Treatment of
dimeric 9H-9-borafluorene with Li metal in toluene yields two strikingly
different classes of compounds. One part of the sample reacts in a way similar to
B2H6, thus affording an aryl(hydro)borane cluster reminiscent of the [B3H8](-)
anion. The other part furnishes a dianionic boron-doped graphene flake devoid of
hydrogen substituents at the boron centers and featuring a central B=B bond. A
change in the solvent to THF allows an isolation of this dibenzo[g,p]chrysene
analogue in good yields.
PMID- 25131583
TI - Amyloid structure.
AB - Amyloid fibrils are formed by numerous proteins and peptides that share little
sequence homology. The structures formed are highly ordered and extremely stable,
being composed of beta-sheet structure and stabilized along their length by
hydrogen bonding. The fibrils are formed by several protofilaments that wind
around one another in rope-like structures, lending further strength and
stability to the resulting fibres. The fact that so many proteins and peptides
form amyloid structures under suitable conditions, seems to suggest that the
sequence of the precursor is unimportant. However, it is now clear that side
chains play a central role in forming interactions between several beta-sheets to
further stabilize and regulate the structures. The primary sequence plays a
central role in determining the rate of fibril formation, the stability of the
resulting structure to degradation and the final morphology of the fibrils. The
side chains regulate the elongation and growth, and also the lateral association
of the protofilament and fibrils, having a significant impact on the final
architecture.
PMID- 25131584
TI - The physical chemistry of the amyloid phenomenon: thermodynamics and kinetics of
filamentous protein aggregation.
AB - In this chapter, we present an overview of the kinetics and thermodynamics of
protein aggregation into amyloid fibrils. The perspective we adopt is largely
experimental, but we also discuss recent developments in data analysis and we
show that only a combination of well-designed experiments with appropriate
theoretical modelling is able to provide detailed mechanistic insight into the
complex pathways of amyloid formation. In the first part of the chapter, we
describe measurements of the thermodynamic stability of the amyloid state with
respect to the soluble state of proteins, as well as the magnitude and origin of
this stability. In the second part, we discuss in detail the kinetics of the
individual molecular steps in the overall mechanism of the conversion of soluble
protein into amyloid fibrils. Finally, we highlight the effects of external
factors, such as salt type and concentration, chemical denaturants and molecular
chaperones on the kinetics of aggregation.
PMID- 25131585
TI - Predicting aggregation-prone sequences in proteins.
AB - Owing to its association with a diverse range of human diseases, the determinants
of protein aggregation are studied intensively. It is generally accepted that the
effective aggregation tendency of a protein depends on many factors such as
folding efficiency towards the native state, thermodynamic stability of that
conformation, intrinsic aggregation propensity of the polypeptide sequence and
its ability to be recognized by the protein quality control system. The intrinsic
aggregation propensity of a polypeptide sequence is related to the presence of
short APRs (aggregation-prone regions) that self-associate to form intermolecular
beta-structured assemblies. These are typically short sequence segments (5-15
amino acids) that display high hydrophobicity, low net charge and a high tendency
to form beta-structures. As the presence of such APRs is a prerequisite for
aggregation, a plethora of methods have been developed to identify APRs in amino
acid sequences. In the present chapter, the methodological basis of these
approaches is discussed, as well as some practical applications.
PMID- 25131582
TI - Genetic analysis of colon tumors induced by a dietary carcinogen PhIP in CYP1A
humanized mice: Identification of mutation of beta-catenin/Ctnnb1 as the driver
gene for the carcinogenesis.
AB - Replacing mouse Cyp1a with human CYP1A enables the humanized CYP1A mice to mimic
human metabolism of the dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5
b]pyridine (PhIP), by N(2) -hydroxylation to a proximate carcinogen. Our previous
study demonstrated that PhIP, combined with the dextrin sulfate sodium (DSS)
induced colitis, induces colon carcinogenesis in hCYP1A mice. Here, we employed
whole exome sequencing and found multiple gene mutations in PhIP/DSS-induced
colon tumors. Mutations in the exon 3 of Ctnnb1/beta-catenin, however, were the
predominant events. We further sequenced the key fragments of Apc, Ctnnb1, and
Kras, because mutations of these genes in the humans are commonly found as the
drivers of colorectal cancer. Mutations on either codon 32 or 34 in the exon 3 of
Ctnnb1 were found in 39 out of 42 tumors, but no mutation was found in either Apc
or Kras. The sequence context of codons 32 and 34 suggests that PhIP targets +3G
in a TGGA motif of Ctnnb1. Since mutations that activate Wnt signal is a major
driving force for human colorectal cancers, we conclude that the mutated beta
catenin is the driver in PhIP/DSS-induced colon carcinogenesis. This result
suggests that the colon tumors in hCYP1A mice mimic human colorectal
carcinogenesis not only in the dietary etiology involving PhIP, but also in the
aberrant activation of the Wnt signaling pathway as the driving force.
PMID- 25131586
TI - Protein folding, misfolding and quality control: the role of molecular
chaperones.
AB - Cells have to cope with stressful conditions and adapt to changing environments.
Heat stress, heavy metal ions or UV stress induce damage to cellular proteins and
disturb the balanced status of the proteome. The adjusted balance between folded
and folding proteins, called protein homoeostasis, is required for every aspect
of cellular functionality. Protective proteins called chaperones are expressed
under extreme conditions in order to prevent aggregation of cellular proteins and
safeguard protein quality. These chaperones co-operate during de novo folding,
refolding and disaggregation of damaged proteins and in many cases refold them to
their functional state. Even under physiological conditions these machines
support protein homoeostasis and maintain the balance between de novo folding and
degradation. Mutations generating unstable proteins, which are observed in
numerous human diseases such as Alzheimer's disease, Huntington's disease,
amyotrophic lateral sclerosis and cystic fibrosis, also challenge the protein
quality control system. A better knowledge of how the protein homoeostasis system
is regulated will lead to an improved understanding of these diseases and provide
potential targets for therapy.
PMID- 25131587
TI - Insights into amyloid disease from fly models.
AB - The formation of amyloid aggregates is a feature of most, if not all, polypeptide
chains. In vivo modelling of this process has been undertaken in the fruitfly
Drosophila melanogaster with remarkable success. Models of both neurological and
systemic amyloid diseases have been generated and have informed our understanding
of disease pathogenesis in two main ways. First, the toxic amyloid species have
been at least partially characterized, for example in the case of the Abeta
(amyloid beta-peptide) associated with Alzheimer's disease. Secondly, the genetic
underpinning of model disease-linked phenotypes has been characterized for a
number of neurodegenerative disorders. The current challenge is to integrate our
understanding of disease-linked processes in the fly with our growing knowledge
of human disease, for the benefit of patients.
PMID- 25131588
TI - Yeast models for amyloid disease.
AB - Saccharomyces cerevisiae (baker's yeast) is a well-established eukaryotic model
organism, which has significantly contributed to our understanding of mechanisms
that drive numerous core cellular processes in higher eukaryotes. Moreover, this
has led to a greater understanding of the underlying pathobiology associated with
disease in humans. This tractable model offers an abundance of analytical
capabilities, including a vast array of global genetics and molecular resources
that allow genome-wide screening to be carried out relatively simply and cheaply.
A prime example of the versatility and potential for applying yeast technologies
to explore a mammalian disease is in the development of yeast models for amyloid
diseases such as Alzheimer's, Parkinson's and Huntington's. The present chapter
provides a broad overview of high profile human neurodegenerative diseases that
have been modelled in yeast. We focus on some of the most recent findings that
have been developed through genetic and drug screening studies using yeast
genomic resources. Although this relatively simple unicellular eukaryote seems
far removed from relatively complex multicellular organisms such as mammals, the
conserved mechanisms for how amyloid exhibits toxicity clearly underscore the
value of carrying out such studies in yeast.
PMID- 25131589
TI - Amyloid beta-peptide and Alzheimer's disease.
AB - One of the hallmarks of AD (Alzheimer's disease) is the formation of senile
plaques in the brain, which contain fibrils composed of Abeta (amyloid beta
peptide). According to the 'amyloid cascade' hypothesis, the aggregation of Abeta
initiates a sequence of events leading to the formation of neurofibrillary
tangles, neurodegeneration, and on to the main symptom of dementia. However,
emphasis has now shifted away from fibrillar forms of Abeta and towards smaller
and more soluble 'oligomers' as the main culprit in AD. The present chapter
commences with a brief introduction to the disease and its current treatment, and
then focuses on the formation of Abeta from the APP (amyloid precursor protein),
the genetics of early-onset AD, which has provided strong support for the amyloid
cascade hypothesis, and then on the development of new drugs aimed at reducing
the load of cerebral Abeta, which is still the main hope for providing a more
effective treatment for AD in the future.
PMID- 25131590
TI - The physiology and pathology of microtubule-associated protein tau.
AB - Tau belongs to the family of microtubule-associated proteins predominantly
expressed in neurons where they play an important role in promoting microtubule
assembly and stabilizing microtubules. In addition, tau proteins interact with
other cytoskeletal elements to allow spacing between microtubules. Recent studies
have shown that tau is also actively involved in regulating cell viability and
activity. Translated from a single gene located on chromosome 17q21, six isoforms
of tau are produced by alternative splicing in adult human brain. Due to multiple
post-translational modifications, heterogeneous tau species with a wide range of
apparent molecular masses have been observed by denaturing polyacrylamide-gel
electrophoresis. Since tau gene mutations and abnormal post-translational
modifications have been detected in over 20 neurodegenerative disorders, namely
the tauopathies, tau has gained widespread attention as a target protein in
Alzheimer's disease and other neurodegenerative disorders. In the present
chapter, research progress regarding physiology and pathology of tau is reviewed,
particularly in terms of the role of post-translational modification.
PMID- 25131591
TI - Role of alpha-synuclein in neurodegeneration: implications for the pathogenesis
of Parkinson's disease.
AB - alpha-Syn (alpha-synuclein) is a small soluble acidic protein that is extensively
expressed in the nervous system. Genetic, clinical and experimental studies
demonstrate that alpha-syn is strongly implicated in the pathogenesis of PD
(Parkinson's disease). However, the pathogenic mechanism remains elusive. In the
present chapter, we first describe the normal expression and potential
physiological functions of alpha-syn. Then, we introduce recent research progress
related to the pathogenic role of alpha-syn in PD, with special emphasis on how
alpha-syn oligomers cause the preferential degeneration of dopaminergic neurons
in the substantia nigra and the spreading of alpha-syn pathology in the brain of
PD patients.
PMID- 25131592
TI - Oligomers of alpha-synuclein: picking the culprit in the line-up.
AB - In the present chapter, we discuss the key findings on alphasyn (alpha-synuclein)
oligomers from a biophysical point of view. Current structural methods cannot
provide a high-resolution structure of alphasyn oligomers due to their size,
heterogeneity and tendency to aggregate. However, a low-resolution structure of a
stable alphasyn oligomer population is emerging based on compelling data from
different research groups. alphasyn oligomers are normally observed during the
formation of amyloid fibrils and we discuss how they are connected to this
process. Another important topic is the interaction of alphasyn oligomers and
membranes, and we will discuss the evidence which suggests that this interaction
might be essential in the pathogenesis of Parkinson's disease and other
neurodegenerative disorders. Finally, we present a remarkable example of how
small molecules are able to stabilize non-amyloid oligomers and how this might be
a potential strategy to inhibit the inherent toxicity of alphasyn oligomers. A
major challenge is to link the very complex oligomerization pathways seen in
clever experiments in vitro with what actually happens in the cell. With the
tremendous developments in optical microscopy in mind, we believe that it will be
possible to make this link very soon.
PMID- 25131593
TI - Many roads lead to Rome? Multiple modes of Cu,Zn superoxide dismutase
destabilization, misfolding and aggregation in amyotrophic lateral sclerosis.
AB - ALS (amyotrophic lateral sclerosis) is a fatal neurodegenerative syndrome
characterized by progressive paralysis and motor neuron death. Although the
pathological mechanisms that cause ALS remain unclear, accumulating evidence
supports that ALS is a protein misfolding disorder. Mutations in Cu,Zn-SOD1
(copper/zinc superoxide dismutase 1) are a common cause of familial ALS. They
have complex effects on different forms of SOD1, but generally destabilize the
protein and enhance various modes of misfolding and aggregation. In addition,
there is some evidence that destabilized covalently modified wild-type SOD1 may
be involved in disease. Among the multitude of misfolded/aggregated species
observed for SOD1, multiple species may impair various cellular components at
different disease stages. Newly developed antibodies that recognize different
structural features of SOD1 represent a powerful tool for further unravelling the
roles of different SOD1 structures in disease. Evidence for similar cellular
targets of misfolded/aggregated proteins, loss of cellular proteostasis and cell
cell transmission of aggregates point to common pathological mechanisms between
ALS and other misfolding diseases, such as Alzheimer's, Parkinson's and prion
diseases, as well as serpinopathies. The recent progress in understanding the
molecular basis for these devastating diseases provides numerous avenues for
developing urgently needed therapeutics.
PMID- 25131595
TI - Prion disease and the 'protein-only hypothesis'.
AB - Prion disease is the only naturally occurring infectious protein misfolding
disorder. The chemical nature of the infectious agent has been debated for more
than half a century. Early studies on scrapie suggested that the unusual
infectious agent might propagate in the absence of nucleic acid. The 'protein
only hypothesis' provides a theoretical model to explain how a protein self
replicates without nucleic acid, which predicts that a prion, the proteinaceous
infectious agent, propagates by converting its normal counterpart into the
likeness of itself. Decades of studies have provided overwhelming evidence to
support this hypothesis. The latest advances in generating infectious prions with
bacterially expressed recombinant prion protein in the presence of cofactors not
only provide convincing evidence supporting the 'protein-only hypothesis', but
also indicate a role of cofactors in forming prion infectivity and encoding prion
strains. In the present chapter, we review the literature regarding the chemical
nature of the infectious agent, describe recent achievements in proving the
'protein-only hypothesis', and discuss the remaining questions in this research
area.
PMID- 25131594
TI - Spontaneous self-assembly of pathogenic huntingtin exon 1 protein into amyloid
structures.
AB - PolyQ (polyglutamine) diseases such as HD (Huntington's disease) or SCA1
(spinocerebellar ataxia type 1) are neurodegenerative disorders caused by
abnormally elongated polyQ tracts in human proteins. PolyQ expansions promote
misfolding and aggregation of disease-causing proteins, leading to the appearance
of nuclear and cytoplasmic inclusion bodies in patient neurons. Several lines of
experimental evidence indicate that this process is critical for disease
pathogenesis. However, the molecular mechanisms underlying spontaneous polyQ
containing aggregate formation and the perturbation of neuronal processes are
still largely unclear. The present chapter reviews the current literature
regarding misfolding and aggregation of polyQ-containing disease proteins. We
specifically focus on studies that have investigated the amyloidogenesis of polyQ
containing HTTex1 (huntingtin exon 1) fragments. These protein fragments are
disease-relevant and play a critical role in HD pathogenesis. We outline
potential mechanisms behind mutant HTTex1 aggregation and toxicity, as well as
proteins and small molecules that can modify HTTex1 amyloidogenesis in vitro and
in vivo. The potential implications of such studies for the development of novel
therapeutic strategies are discussed.
PMID- 25131596
TI - Amyloid diseases of yeast: prions are proteins acting as genes.
AB - The unusual genetic properties of the non-chromosomal genetic elements [URE3] and
[PSI+] led to them being identified as prions (infectious proteins) of Ure2p and
Sup35p respectively. Ure2p and Sup35p, and now several other proteins, can form
amyloid, a linear ordered polymer of protein monomers, with a part of each
molecule, the prion domain, forming the core of this beta-sheet structure.
Amyloid filaments passed to a new cell seed the conversion of the normal form of
the protein into the same amyloid form. The cell's phenotype is affected, usually
from the deficiency of the normal form of the protein. Solid-state NMR studies
indicate that the yeast prion amyloids are in-register parallel beta-sheet
structures, in which each residue (e.g. Asn35) forms a row along the filament
long axis. The favourable interactions possible for aligned identical hydrophilic
and hydrophobic residues are believed to be the mechanism for propagation of
amyloid conformation. Thus, just as DNA mediates inheritance by templating its
own sequence, these proteins act as genes by templating their conformation.
Distinct isolates of a given prion have different biological properties,
presumably determined by differences between the amyloid structures. Many lines
of evidence indicate that the Saccharomyces cerevisiae prions are pathological
disease agents, although the example of the [Het-s] prion of Podospora anserina
shows that a prion can have beneficial aspects.
PMID- 25131597
TI - Functional amyloid: widespread in Nature, diverse in purpose.
AB - Amyloids are insoluble fibrillar protein deposits with an underlying cross-beta
structure initially discovered in the context of human diseases. However, it is
now clear that the same fibrillar structure is used by many organisms, from
bacteria to humans, in order to achieve a diverse range of biological functions.
These functions include structure and protection (e.g. curli and chorion
proteins, and insect and spider silk proteins), aiding interface transitions and
cell-cell recognition (e.g. chaplins, rodlins and hydrophobins), protein control
and storage (e.g. Microcin E492, modulins and PMEL), and epigenetic inheritance
and memory [e.g. Sup35, Ure2p, HET-s and CPEB (cytoplasmic polyadenylation
element-binding protein)]. As more examples of functional amyloid come to light,
the list of roles associated with functional amyloids has continued to expand.
More recently, amyloids have also been implicated in signal transduction [e.g.
RIP1/RIP3 (receptor-interacting protein)] and perhaps in host defence [e.g. aDrs
(anionic dermaseptin) peptide]. The present chapter discusses in detail
functional amyloids that are used in Nature by micro-organisms, non-mammalian
animals and mammals, including the biological roles that they play, their
molecular composition and how they assemble, as well as the coping strategies
that organisms have evolved to avoid the potential toxicity of functional
amyloid.
PMID- 25131598
TI - Meta-analysis of peak wall stress in ruptured, symptomatic and intact abdominal
aortic aneurysms.
AB - BACKGROUND: Abdominal aortic aneurysm (AAA) is an important cause of sudden
death; however, there are currently incomplete means to predict the risk of AAA
rupture. AAA peak wall stress (PWS) can be estimated using finite element
analysis (FEA) methods from computed tomography (CT) scans. The question is
whether AAA PWS can predict AAA rupture. The aim of this systematic review was to
compare PWS in patients with ruptured and intact AAA. METHODS: The MEDLINE
database was searched on 25 May 2013. Case-control studies assessing PWS in
asymptomatic intact, and acutely symptomatic or ruptured AAA from CT scans using
FEA were included. Data were extracted independently. A random-effects model was
used to calculate standard mean differences (SMDs) for PWS measurements. RESULTS:
Nine studies assessing 348 individuals were identified and used in the meta
analysis. Results from 204 asymptomatic intact and 144 symptomatic or ruptured
AAAs showed that PWS was significantly greater in the symptomatic/ ruptured AAAs
compared with the asymptomatic intact AAAs (SMD 0.95, 95 per cent confidence
interval 0.71 to 1.18; P < 0.001). The findings remained significant after
adjustment for mean systolic blood pressure, standardized at 120 mmHg (SMD 0.68,
0.39 to 0.96; P < 0.001). Minimal heterogeneity between studies was noted (I(2)
= 0 per cent). CONCLUSION: This study suggests that PWS is greater in symptomatic
or ruptured AAA than in asymptomatic intact AAA.
PMID- 25131599
TI - Prostaglandin E2 as a read out for endotoxin detection in a bovine whole blood
assay.
AB - The detection of endotoxin contamination is an essential part of drug safety
testing. The rabbit pyrogen test (RPT), the limulus amoebocyte lysate (LAL) test,
and the monocyte activation test (MAT) are established methods for the detection
of pyrogens. However, the RPT is insufficiently standardized; the LAL test is
solely capable of identifying the presence of endotoxins, whereas the use of the
MAT is limited by the availability of human blood. Here, we introduce a new
procedure for testing endotoxin contamination using prostaglandin E2 (PGE2 )
release from bovine whole blood. We incubated bovine whole blood overnight with
lipopolysaccharide (LPS) from Escherichia coli 0111:B4, concentrations ranging
from 1.56 to 12.5 pg/mL, and found significantly increased PGE2 production for
even the lowest LPS concentrations. Testing the possibility of storing the blood
at 4 degrees C before use also yielded positive results as 1.56 pg/mL still
significantly increased PGE2 production, thus suggesting some flexibility of the
assay regarding time. These results emphasize the potential of using bovine whole
blood for highly sensitive endotoxin testing. As a perspective, currently ongoing
research aims to show whether the assay is also capable of detecting nonendotoxin
pyrogens.
PMID- 25131600
TI - Dietary total antioxidant capacity is associated with leukocyte telomere length
in a children and adolescent population.
AB - BACKGROUND & AIMS: Oxidative stress and inflammation seem to be potential
underlying mechanisms for telomere attrition. A lack of specific antioxidants is
believed to increase free radical damage and a greater risk for telomere
shortening. Our aim was to evaluate the relationship between diet and leukocyte
telomere length in a cross-sectional study of children and adolescents. We
hypothesized that dietary total antioxidant capacity would be positively
associated with telomere length. METHODS: Telomere length was measured by
quantitative real-time polymerase chain reaction in 287 participants (55% males,
6-18 years), who were randomly selected from the GENOI study. RESULTS: A positive
correlation between dietary total antioxidant capacity and telomere length (r =
0.157, p = 0.007) was found after adjustment for age and energy intake. However,
higher white bread consumption was associated with shorter telomeres (beta =
0.204, p = 0.002) in fully-adjusted models. Interestingly, those individuals who
had simultaneously higher dietary total antioxidant capacity and lower white
bread consumption significantly presented the longest telomeres. Moreover, the
multivariable-adjusted odds ratio for very short telomeres was 0.30 for dietary
total antioxidant capacity (p = 0.023) and 1.37 for white bread (p = 0.025).
CONCLUSION: It was concluded that longer telomeres were associated with higher
dietary total antioxidant capacity and lower white bread consumption in Spanish
children and adolescents. These findings might open a new line of investigation
about the potential role of an antioxidant diet in maintaining telomere length.
PMID- 25131601
TI - Routes for early enteral nutrition after esophagectomy. A systematic review.
AB - BACKGROUND: Early enteral feeding following surgery can be given orally, via a
jejunostomy or via a nasojejunal tube. However, the best feeding route following
esophagectomy is unclear. OBJECTIVES: To determine the best route for enteral
nutrition following esophagectomy regarding anastomotic leakage, pneumonia,
percentage meeting the nutritional requirements, weight loss, complications of
tube feeding, mortality, patient satisfaction and length of hospital stay.
DESIGN: A systematic literature review following PRISMA and MOOSE guidelines.
RESULTS: There were 17 eligible studies on early oral intake, jejunostomy or
nasojejunal tube feeding. Only one nonrandomized study (N = 133) investigated
early oral feeding specifically following esophagectomy. Early oral feeding was
associated with a reduced length of stay with delayed oral feeding, without
increased complication rates. Postoperative nasojejunal tube feeding was not
significantly different from jejunostomy tube feeding regarding complications or
catheter efficacy in the only randomised trial on this subject (N = 150).
Jejunostomy tube feeding outcome was reported in 12 non-comparative studies (N =
3293). It was effective in meeting short-term nutritional requirements, but major
tube-related complications necessitated relaparotomy in 0-2.9% of patients. In
three non-comparative studies (N = 135) on nasojejunal tube feeding only minor
complications were reported, data on nutritional outcome was lacking. Data on
patient satisfaction and long-term nutritional outcome were not found for any of
the feeding routes investigated. CONCLUSION: It is unclear what the best route
for early enteral nutrition is after esophagectomy. Especially data regarding
early oral intake are scarce, and phase 2 trials are needed for further
investigation. REGISTRATION: International prospective register of systematic
reviews, CRD42013004032.
PMID- 25131603
TI - Gender differences in perceived stigma of dementia in Chinese Americans.
PMID- 25131602
TI - Changes of hepatic lipid mediators associated with intake of high-fat diet for 12
weeks in endotoxemic rats using LC-ESI-MS/MS.
AB - BACKGROUND & AIMS: It has recently been reported that anti-inflammatory lipid
mediators are increased in the late phase of acute inflammation, whereas
proinflammatory lipid mediators are regulated at the initiation of inflammation.
The purpose of this study was to evaluate changes of hepatic lipid mediators due
to high-fat diet (HFD) feeding in endotoxemic rats. METHODS: Male Wistar rats
were fed either HFD or control diet for 12 weeks, and were then killed 0, 1.5,
and 6 h after lipopolysaccharide (LPS) injection. Analyses included lipidomics
assessment of mediators using liquid chromatography-electrospray ionization/multi
stage mass spectrometry; measuring expression of hepatic polyunsaturated fatty
acid (PUFA)-oxidizing enzyme, tumor necrosis factor (TNF)-alpha, interleukin (IL)
6, and inducible nitric oxide synthase mRNA levels; blood biochemical tests; and
liver histology. RESULTS: HFD feeding worsened liver injury, increased expression
of TNF-alpha and IL-6 mRNA, and increased oxidative stress after LPS injection.
PUFA-oxidizing enzymes were higher in HFD-fed rats after LPS injection. The
proinflammatory prostaglandin (PG)E2 and thromboxane B2 were increased 1.5 h
after LPS injection, and had decreased by 6 h in HFD-fed rats. In contrast,
potent pro-resolving resolvins derived from eicosapentaenoic acid and
docosahexaenoic acid were not detected, but anti-inflammatory epoxyeicosatrienoic
acids, lipoxin A4, and 15-deoxy-PGJ2 were increased after LPS injection in HFD
fed rats. CONCLUSIONS: HFD feeding for 12 weeks enhanced proinflammatory lipid
mediators 1.5 h after LPS injection suggesting relation to liver injury.
PMID- 25131604
TI - Depression, anxiety, and memory impairment among geriatric inpatient subjects.
PMID- 25131606
TI - Nurses are essential players in all health and policy arenas.
PMID- 25131607
TI - Ethical dilemmas: the challenge of advocating for human rights.
PMID- 25131608
TI - The power of unity.
PMID- 25131610
TI - C. pneumoniae disrupts eNOS trafficking and impairs NO production in human aortic
endothelial cells.
AB - Endothelial nitric oxide synthase (eNOS) generated NO plays a crucial
physiological role in the regulation of vascular tone. eNOS is a constitutively
expressed synthase whose enzymatic function is regulated by dual acylation,
phosphorylation, protein-protein interaction and subcellular localization. In
endothelial cells, the enzyme is primarily localized to the Golgi apparatus (GA)
and the plasma membrane where it binds to caveolin-1. Upon stimulation, the
enzyme is translocated from the plasma membrane to the cytoplasm where it
generates NO. When activation of eNOS ceases, the majority of the enzyme is
recycled back to the membrane fraction. An inability of eNOS to cycle between the
cytosol and the membrane leads to impaired NO production and vascular
dysfunction. Chlamydia pneumoniae is a Gram-negative obligate intracellular
bacterium that primarily infects epithelial cells of the human respiratory tract,
but unlike any other chlamydial species, C. pneumoniae displays tropism toward
atherosclerotic tissues. In this study, we demonstrate that C. pneumoniae
inclusions colocalize with eNOS, and the microorganism interferes with
trafficking of the enzyme from the GA to the plasma membrane in primary human
aortic endothelial cells. This mislocation of eNOS results in significant
inhibition of NO release by C. pneumoniae-infected cells. Furthermore, we show
that the distribution of eNOS in C. pneumoniae-infected cells is altered due to
an intimate association of the Golgi complex with chlamydial inclusions rather
than by direct interaction of the enzyme with the chlamydial inclusion membrane.
PMID- 25131605
TI - The safe passage study: design, methods, recruitment, and follow-up approach.
AB - BACKGROUND: The Safe Passage Study is a large, prospective, multidisciplinary
study designed to (1) investigate the association between prenatal alcohol
exposure, sudden infant death syndrome (SIDS), and stillbirth, and (2) determine
the biological basis of the spectrum of phenotypic outcomes from exposure, as
modified by environmental and genetic factors that increase the risk of
stillbirth, SIDS, and in surviving children, fetal alcohol spectrum disorders.
METHODS: The results provided are based on an interim assessment of 6004 women
enrolled, out of the 12,000 projected, from the Northern Plains, US, and Cape
Town, South Africa, areas known to be of high risk for maternal drinking during
pregnancy. Research objectives, study design, and descriptive statistics,
including consent, recruitment, and retention information, are provided. RESULTS:
Overall visit compliance is 87%, and includes prenatal, delivery/newborn, and
postnatal contacts through 1 year post-delivery. Pregnancy outcome ascertainment
is 98% prior to medical chart review; less than 2% of women withdraw. Consent for
the use of DNA and placental tissue exceed 94%, and consent to participate in the
autopsy portion of the study is 71%. CONCLUSIONS: The Safe Passage Study is the
first multi-site study of SIDS and stillbirth to integrate prospectively
collected exposure information with multidisciplinary biological information in
the same maternal and fetal/infant dyad using a common protocol. Essential
components of the study design and its success are close ties to the community
and rigorous systems and processes to ensure compliance with the study protocol
and procedures.
PMID- 25131611
TI - Potential efficacy of dopamine loaded-PVP/PAA nanogel in experimental models of
Parkinsonism: possible disease modifying activity.
AB - This study aimed to investigate the ability of dopamine (DA)-loaded
polyvinylpyrrolidone-poly(acrylic acid) (PVP/PAAc) nanogel [synthesized by gamma
(gamma) radiation-induced template polymerization] [Nano-DA] to deliver DA across
the blood brain barrier, and to evaluate the efficacy and safety of the acute and
subchronic administration of Nano-DA in modulating motor activity and/or the
biochemical changes in rat brain; induced by different models of Parkinsonism. In
this respect, (PVP/PAAc) nanogel was synthesized by gamma radiation-induced
polymerization of acrylic acid (AAc) in an aqueous solution of PVP as a template
polymer, and then, it was used as a nano-drug carrier for DA. The PVP/PAAc and
(PVP/PAAc loaded-DA nanogel particles were characterized by dynamic light
scattering, infrared spectroscopy, and field emission-scanning electron
microscopy. The loaded gel was administered in different doses and dosing
regimens to Parkinsonian rats, and the catalepsy score and striatal DA levels
were assessed. Then, the potential disease-modifying activity of this form of DA
was investigated, through the assessment of the improvement in mitochondrial
function, following the subchronic administration of Nano-DA to Parkinsonian
rats. Significant disease-modifying effects were observed upon the administration
of Nano-DA; in addition to normalization in their motor activity.
PMID- 25131613
TI - Thoracic manifestations of connective tissue diseases.
AB - Connective tissue diseases (CTDs) comprise several immunologic systemic
disorders, each of which associated with a particular set of clinical
manifestations and autoimmune profile. CTDs may cause numerous thoracic
abnormalities, which vary in frequency and pattern according to the underlying
disorder. The CTDs that most commonly involve the respiratory system are
progressive systemic sclerosis, systemic lupus erythematosus, rheumatoid
arthritis, Sjogren syndrome, polymyositis, dermatomyositis, and mixed connective
tissue disease. Pulmonary abnormalities in this group of patients may result from
CTD-related lung disease or treatment complications, namely drug toxicity and
opportunistic infections. The most important thoracic manifestations of CTDs are
interstitial lung disease and pulmonary arterial hypertension, with nonspecific
interstitial pneumonia being the most common pattern of interstitial lung
disease. High-resolution computed tomography is a valuable tool in the initial
evaluation and follow-up of patients with CTDs. As such, general knowledge of the
most common high-resolution computed tomographic features of CTD-related lung
disease allows the radiologist to contribute to better patient management.
PMID- 25131614
TI - Coprinopsis atramentaria extract, its organic acids, and synthesized glucuronated
and methylated derivatives as antibacterial and antifungal agents.
AB - Despite the available data regarding antimicrobial activity of phenolic acids,
studies dealing with the effects of their metabolites or derivatives are scarce.
Therefore, the antimicrobial and demelanizing activities of Coprinopsis
atramentaria extract, its organic acids, and methylated and glucuronated
derivatives were evaluated. The antifungal activity was stronger than the
antibacterial effects. In general, individual compounds (mostly organic acids)
exhibited higher activity than the extract and even higher than the standards
used in the assays. Methylated derivatives presented the highest demelanizing
activity toward Aspergillus niger, A. fumigatus and Penicillium verrucosum var.
cyclopium. The inclusion of methyl groups in the parental compound (CoAM1, CoAM2
and CoAM3) strongly increased antibacterial and antifungal activities of CoA,
while the inclusion of acetyl groups (CoAGP) increased the antifungal activity
but the antibacterial properties were maintained. For HA and CA, the inclusion of
methyl groups (HAM1, HAM2, HAM3 and CAM) increased the demelanizing activity, but
decreased the antimicrobial properties. The present work contributes to the
knowledge of the mechanisms involved in the antimicrobial properties of organic
acids namely, phenolic acids, usually present in mushrooms. Organic acids, and
methylated and glucuronated derivatives could be used as antimicrobial agents.
PMID- 25131615
TI - Molecular characteristics of Staphylococcus aureus associated with chronic
rhinosinusitis.
AB - The anterior nares have been regarded as the major carriage site of
Staphylococcus aureus. From here, the organism can spread to other parts of the
body where it might act as harmless commensal or cause mild to severe infections.
Nasal sinuses are normally sterile, but in patients with chronic rhinosinusitis
(CRS), the finding of S. aureus in maxillary sinus cultures is common. Isolates
were obtained from the nares and maxillary sinus of patients with CRS and the
nares of healthy controls. A significantly higher frequency of S. aureus was
found in nares samples from patients (24/42) compared to controls (16/57) (p =
0.004). There is no consensus regarding whether S. aureus is a relevant pathogen
in CRS. A DNA microarray was used to investigate the prevalence of S. aureus
virulence genes with focus on staphylococcal enterotoxins, toxic shock syndrome
toxin-1, agr types, and cell wall-associated proteins. The genotyping of S.
aureus isolates revealed only small and non-significant differences in gene
prevalence between isolates collected from patients with CRS and those collected
from healthy nasal carriers. This study provides an increased knowledge of the
genetic pattern of virulence genes among S. aureus collected in CRS.
PMID- 25131612
TI - Blockade of 2-arachidonoylglycerol hydrolysis produces antidepressant-like
effects and enhances adult hippocampal neurogenesis and synaptic plasticity.
AB - The endocannabinoid ligand 2-arachidonoylglycerol (2-AG) is inactivated primarily
by monoacylglycerol lipase (MAGL). We have shown recently that chronic treatments
with MAGL inhibitor JZL184 produce antidepressant- and anxiolytic-like effects in
a chronic unpredictable stress (CUS) model of depression in mice. However, the
underlying mechanisms remain poorly understood. Adult hippocampal neurogenesis
has been implicated in animal models of anxiety and depression and behavioral
effects of antidepressants. We tested whether CUS and chronic JZL184 treatments
affected adult neurogenesis and synaptic plasticity in the dentate gyrus (DG) of
mouse hippocampus. We report that CUS induced depressive-like behaviors and
decreased the number of bromodeoxyuridine-labeled neural progenitor cells and
doublecortin-positive immature neurons in the DG, while chronic JZL184 treatments
prevented these behavioral and cellular deficits. We also investigated the
effects of CUS and chronic JZL184 on a form long-term potentiation (LTP) in the
DG known to be neurogenesis-dependent. CUS impaired LTP induction, whereas
chronic JZL184 treatments restored LTP in CUS-exposed mice. These results suggest
that enhanced adult neurogenesis and long-term synaptic plasticity in the DG of
the hippocampus might contribute to antidepressant- and anxiolytic-like
behavioral effects of JZL184.
PMID- 25131616
TI - Connections of the limbic network: a corticocortical evoked potentials study.
AB - Papez proposed a network for higher brain function, which is termed the limbic
network. However, the in vivo human limbic network has not been established. We
investigated the connectivity of the human limbic system using corticocortical
evoked potential (CCEP). This retrospective analysis included 28 patients with
medically intractable focal epilepsy who underwent stereoelectroencephalography
(SEEG) and CCEP. Alternating 1 Hz electrical stimuli were delivered to parts of
the limbic system [anterior and posterior hippocampus, temporal pole,
parahippocampal gyrus (PHG), amygdala, anterior (ACG) and posterior cingulate
gyrus (PCG), medial and lateral orbitofrontal cortex (OF)]. A total of 40-60
stimuli were averaged in each trial to obtain CCEP responses. CCEP distributions
were evaluated by calculating the root mean square (RMS) of CCEP responses.
Anterior hippocampal stimulation elicited prominent CCEP responses in medial and
lateral temporal structures, PCG, medial OF and insula over the ipsilateral
hemisphere. Posterior hippocampal stimulation induced CCEP responses in the
ipsilateral medial and lateral temporal structures and PCG. The findings also
revealed connections from temporal pole to the ipsilateral medial temporal
structures, and connections from PHG to the ipsilateral hippocampus and PCG. The
amygdala projected to broad areas including the ipsilateral medial and lateral
temporal structures, medial and lateral frontal areas, the cingulate gyrus,
insula and inferior parietal lobule. ACG and PCG showed connections to the
ipsilateral medial fronto-parietal areas and connections to bilateral medial
temporo-parieto-occipital and lateral parieto-occipital areas, respectively.
Medial and lateral OF stimulation induced responses in the adjacent cortices.
This study revealed that various regions within the limbic network are intimately
connected in reverberating circuits and are linked to specific ipsilateral and
contralateral regions, which may reflect distinct functional roles.
PMID- 25131617
TI - Serum microRNA-124 is a novel biomarker for liver necroinflammation in patients
with chronic hepatitis B virus infection.
AB - Patients with chronic hepatitis B virus (HBV) infection and normal or mildly
increased transaminases may have sustained significant liver damage, as verified
by liver biopsy. However, no suitable noninvasive method exists for identifying
liver necroinflammation in such patients. We aimed to investigate the power of
microRNA-124 as a novel biomarker for liver necroinflammation. A total of 131
recruited patients with chronic HBV infection underwent liver biopsy for grading
of necroinflammation (G) and staging of fibrosis (S). Thirty healthy individuals
were included as controls (HCs). Serum microRNA-124 and microRNA-122 levels were
measured using qRT-PCR. Forty-five patients from the study population receiving
entecavir therapy were monitored for changes in serum microRNA-124 levels in
association with improved liver histology. The capacity of serum microRNA-124
levels in discriminating the grade of liver necroinflammation was compared with
alanine aminotransferase (ALT) with liver biopsy validation. Serum microRNA-124
levels were significantly higher in patients with chronic HBV infection than in
HCs (P < 0.0001). Patients with considerable liver necroinflammation (G >= 2) had
significantly higher serum miRNA-124 levels than those without or with mild
necroinflammation (P < 0.0001). After 48 weeks of antiviral therapy, serum
microRNA-124 levels considerably declined in 45 patients (P < 0.0001), which were
associated with histological improvement. In patients with normal ALT and a serum
HBV DNA load >10(4) copies/mL, receiver operating characteristic (ROC) curve of
serum microRNA-124 levels yielded an area under ROC curve (AUC) of 0.840, with
58.3% sensitivity and 91.7% specificity in discriminating between moderate-to
severe liver necroinflammation (G >= 2).
PMID- 25131618
TI - Neuroproteomics in the auditory brainstem: candidate proteins for ultrafast and
precise information processing.
AB - In the mammalian auditory brainstem, the cochlear nuclear complex (CN) and the
superior olivary complex (SOC) feature structural and functional specializations
for ultrafast (<1 ms) and precise information processing. Their proteome, the
basis for structure and function, has been rarely analyzed so far. Here we
identified and quantified the protein profiles of three major auditory brainstem
regions of adult rats, the CN, the SOC, and the inferior colliculus (IC). The
rest of the brain served as a reference. Via label-free quantitative mass
spectrometry and 2-D DIGE/MALDI-MS, we identified 584 and 297 proteins in the
plasma membrane/synaptic vesicle proteome and the cytosolic proteome,
respectively. 'Region-typical' proteins, i.e., those with higher abundance in one
region than in the other three, were considered candidates for functional
specializations. Key proteins were validated via Western blots and
immunohistochemistry. Functional annotation clustering revealed an
overrepresentation of neurofilament proteins among the CN+SOC-typical proteins.
These are related to regulation of axon diameter and, thereby, conduction
velocity. Interestingly, the sets of synapse-associated proteins differed between
regions. For example, synaptotagmin-2 (Syt2), a Ca2+ sensor for fast exocytosis,
was CN+SOC+IC-typical, whereas Syt1 was CN+SOC+IC-atypical. Together, our
quantitative comparison of protein profiles has revealed several interesting
candidate proteins for ultrafast and precise information processing.
PMID- 25131620
TI - Pilot study to assess measures to be used in the prospective audit of the
management of foot ulcers in people with diabetes.
AB - AIM: To design and test a methodology for assessing aspects of the management of
foot disease in diabetes. METHODS: A national working group devised pilot
datasets that may be used to document the process of management of active
ulceration. Participating volunteer specialist units throughout England were
required to characterize newly presenting people with diabetic foot ulcers using
a standard questionnaire comprising the dataset and to document outcomes at 6 and
12 months. Semi-structured interviews were later conducted with the volunteers at
the units. RESULTS: A total of 23 units recorded baseline data on 652 people with
incident foot ulcers; valid outcome data were available for 541 people (83.0%).
Of the 541 index ulcers, 351 (64.9%) healed within 24 weeks, with a median time
to healing of 63 days. Ulcer site and depth and peripheral arterial disease were
associated with differing ulcer healing rates. By contrast, baseline demographic
characteristics were not independently associated with healing. These were used
to calculate a standardized case-mix adjusted healing ratio. In most units data
collection took < 10 min per person, but participants reported that the burden of
local data collection was still excessive. CONCLUSION: This study confirmed the
feasibility of routine multi-unit comparative assessment of care of the foot in
diabetes, including the generation of meaningful service reports, but for general
use the burden of local data collection will need to be reduced (e.g. by using
linkage to existing national data collections).
PMID- 25131621
TI - Liquid formulation for antibody drugs.
AB - Currently many biopharmaceuticals are in use due to their high efficacy and low
adverse effects. For antibody drug formulation, liquid ones are being
increasingly used. This review focuses on rational liquid antibody formulation
development based on the proposed aggregation mechanism of antibody, considering
colloidal and conformational stabilities. This review also describes the
importance of assessment of physicochemical properties including second virial
coefficient of antibody solutions, for the rational and efficient formulation
development. This article is part of a Special Issue entitled: Recent advances in
molecular engineering of antibody.
PMID- 25131619
TI - Fur homolog regulates Porphyromonas gingivalis virulence under low-iron/heme
conditions through a complex regulatory network.
AB - Porphyromonas gingivalis is a key pathogen responsible for initiation and
progression of chronic periodontitis. Little is known about the regulatory
mechanisms of iron and heme uptake that allow P. gingivalis to express virulence
factors and survive in the hostile environment of the oral cavity, so we
initiated characterization of a P. gingivalis Fur homolog (PgFur). Many Fur
paralogs found in microbial genomes, including Bacteroidetes, confirm that Fur
proteins have a tendency to be subjected to a sub- or even neofunctionalization
process. PgFur revealed extremely high sequence divergence, which could be
associated with its functional dissimilarity in comparison with other Fur
homologs. A fur mutant strain constructed by insertional inactivation exhibited
retarded growth during the early growth phase and a significantly lower tendency
to form a homotypic biofilm on abiotic surfaces. The mutant also showed
significantly weaker adherence and invasion to epithelial cells and macrophages.
Transcripts of many differentially regulated genes identified in the fur mutant
strain were annotated as hypothetical proteins, suggesting that PgFur can play a
novel role in the regulation of gene expression. Inactivation of the fur gene
resulted in decreased hmuY gene expression, increased expression of other hmu
components and changes in the expression of genes encoding hemagglutinins and
proteases (mainly gingipains), HtrA, some extracytoplasmic sigma factors and two
component systems. Our data suggest that PgFur can influence in vivo growth and
virulence, at least in part by affecting iron/heme acquisition, allowing
efficient infection through a complex regulatory network.
PMID- 25131622
TI - Clinical whole exome sequencing in child neurology practice.
AB - OBJECTIVE: Whole exome sequencing (WES) represents a significant breakthrough in
clinical genetics as a powerful tool for etiological discovery in
neurodevelopmental disorders. To better characterize the genetic landscape of
neurodevelopmental disorders, we analyzed patients in our pediatric neurogenetics
clinic who underwent WES. METHODS: We performed a retrospective cohort study on
78 patients with various neurodevelopmental disabilities and unrevealing workup
prior to WES. We characterized their molecular diagnoses, clinical features, and
whether their previous treatment plan changed due to WES results. RESULTS: The
overall presumptive diagnostic rate for our cohort was 41% (n = 32 of 78
patients). Nineteen patients had a single autosomal dominant (AD) disorder, 11
had a single autosomal recessive (AR) disorder, 1 had an X-linked dominant
disorder, and 1 had both an AD and an AR disorder. The 32 patients with
pathogenic or likely pathogenic variants exhibited various neurobehavioral and
neuroimaging abnormalities, including intellectual disability/developmental delay
(n = 28), cerebral palsy-like encephalopathy (n = 11), autism spectrum disorder
(n = 5), delayed/hypomyelination (n = 7), and cerebellar abnormalities (n = 9).
The results of WES affected management for all patients with a presumptive
diagnosis, triggering reproductive planning (n = 27), disease monitoring
initiation (n = 4), investigation of systemic involvement of the disorder(s) (n =
6), alteration of presumed disease inheritance pattern (n = 7), changing of
prognosis (n = 10), medication discontinuation (n = 5) or initiation (n = 2), and
clinical trial education (n = 3). INTERPRETATION: The high diagnostic yield of
WES supports its use in pediatric neurology practices. It may also lead to
earlier diagnosis, impacting medical management, prognostication, and family
planning. WES therefore serves as a critical tool for the child neurologist.
PMID- 25131624
TI - Stationary wavelet transform for under-sampled MRI reconstruction.
AB - In addition to coil sensitivity data (parallel imaging), sparsity constraints are
often used as an additional lp-penalty for under-sampled MRI reconstruction
(compressed sensing). Penalizing the traditional decimated wavelet transform
(DWT) coefficients, however, results in visual pseudo-Gibbs artifacts, some of
which are attributed to the lack of translation invariance of the wavelet basis.
We show that these artifacts can be greatly reduced by penalizing the translation
invariant stationary wavelet transform (SWT) coefficients. This holds with
various additional reconstruction constraints, including coil sensitivity
profiles and total variation. Additionally, SWT reconstructions result in lower
error values and faster convergence compared to DWT. These concepts are
illustrated with extensive experiments on in vivo MRI data with particular
emphasis on multiple-channel acquisitions.
PMID- 25131623
TI - Characterizing pharmacological ligands to study the long-chain fatty acid
receptors GPR40/FFA1 and GPR120/FFA4.
AB - The free fatty acid receptors (FFA) 1 (previously designated GPR40) and FFA4
(previously GPR120) are two GPCRs activated by saturated and unsaturated longer
chain free fatty acids. With expression patterns and functions anticipated to
directly or indirectly promote insulin secretion, provide homeostatic control of
blood glucose and improve tissue insulin sensitivity, both receptors are being
studied as potential therapeutic targets for the control of type 2 diabetes.
Furthermore, genetic and systems biology studies in both humans and mouse models
link FFA4 receptors to diabetes and obesity. Although activated by the same group
of free fatty acids, FFA1 and FFA4 receptors are not closely related and, while
the basis of recognition of fatty acids by FFA1 receptors is similar to that of
the short-chain fatty acid receptors FFA2 and FFA3, the amino acid residues
involved in endogenous ligand recognition by FFA4 receptors are more akin to
those of the sphingosine 1 phosphate receptor S1P1 . Screening and subsequent
medicinal chemistry programmes have developed a number of FFA1 receptor selective
agonists that are effective in promoting insulin secretion in a glucose
concentration-dependent manner, and in lowering blood glucose levels. However,
the recent termination of Phase III clinical trials employing TAK-875/fasiglifam
has caused a setback and raises important questions over the exact nature and
mechanistic causes of the problems. Progress in the identification and
development of highly FFA4 receptor-selective pharmacological tools has been less
rapid and several issues remain to be clarified to fully validate this receptor
as a therapeutic target. Despite this, the ongoing development of a range of
novel ligands offers great opportunities to further unravel the contributions of
these receptors.
PMID- 25131625
TI - In vivo quantitative NMR imaging of fruit tissues during growth using Spoiled
Gradient Echo sequence.
AB - Nondestructive studies of physiological processes in agronomic products require
increasingly higher spatial and temporal resolutions. Nuclear Magnetic Resonance
(NMR) imaging is a non-invasive technique providing physiological and
morphological information on biological tissues. The aim of this study was to
design a robust and accurate quantitative measurement method based on NMR imaging
combined with contrast agent (CA) for mapping and quantifying water transport in
growing cherry tomato fruits. A multiple flip-angle Spoiled Gradient Echo (SGE)
imaging sequence was used to evaluate the intrinsic parameters maps M0 and T1 of
the fruit tissues. Water transport and paths flow were monitored using
Gd(3+)/[Fe(CN)6](3-)/D-mannitol nanoparticles as a tracer. This dynamic study was
carried out using a compartmental modeling. The CA was preferentially accumulated
in the surrounding tissues of columella and in the seed envelopes. The total
quantities and the average volume flow of water estimated are: 198 mg, 1.76
mm(3)/h for the columella and 326 mg, 2.91 mm(3)/h for the seed envelopes. We
demonstrate in this paper that the NMR imaging technique coupled with efficient
and biocompatible CA in physiological medium has the potential to become a major
tool in plant physiology research.
PMID- 25131627
TI - Automatic segmentation of white matter lesions on magnetic resonance images of
the brain by using an outlier detection strategy.
AB - White matter lesions (WMLs) are commonly observed on the magnetic resonance (MR)
images of normal elderly in association with vascular risk factors, such as
hypertension or stroke. An accurate WML detection provides significant
information for disease tracking, therapy evaluation, and normal aging research.
In this article, we present an unsupervised WML segmentation method that uses
Gaussian mixture model to describe the intensity distribution of the normal brain
tissues and detects the WMLs as outliers to the normal brain tissue model based
on extreme value theory. The detection of WMLs is performed by comparing the
probability distribution function of a one-sided normal distribution and a Gumbel
distribution, which is a specific extreme value distribution. The performance of
the automatic segmentation is validated on synthetic and clinical MR images with
regard to different imaging sequences and lesion loads. Results indicate that the
segmentation method has a favorable accuracy competitive with other state-of-the
art WML segmentation methods.
PMID- 25131626
TI - Decreased oxygen saturation in asymmetrically prominent cortical veins in
patients with cerebral ischemic stroke.
AB - Decreased oxygen saturation in asymmetrically prominent cortical veins (APCV)
seen in ischemic stroke has been hypothesized to correlate with an increase of de
oxygenated hemoglobin. Our goal is to quantify magnetic susceptibility to define
APCV by establishing a cutoff above which the deoxyhemoglobin levels are
considered abnormal. A retrospective study was conducted on 26 patients with
acute ischemic stroke in one cerebral hemisphere that exhibited APCV with 30 age-
and sex-matched healthy controls. Quantitative susceptibility mapping (QSM) was
used to calculate the magnetic susceptibility of the cortical veins. A paired t
test was used to compare the susceptibility of the cortical veins in the left and
right hemispheres for healthy controls as well as in the contralateral hemisphere
for stroke patients with APCV. The change in oxygen saturation in the APCV
relative to the contralateral side was calculated after thresholding the
susceptibility using the mean plus two standard deviations of the contralateral
side for each individual. The thresholded susceptibility value of the APCVs in
the stroke hemisphere was 254+/-48 ppb which was significantly higher (p<0.05)
than that in the contralateral hemisphere (123+/-12 ppb) and in healthy controls
(125+/-8 ppb). There was a decrease of oxygen saturation in the APCV ranging from
16% to 44% relative to the veins of the contralateral hemisphere. In conclusion,
APCV seen in SWI correspond to reduced levels of oxygen saturation and these
abnormal veins can be identified using a susceptibility threshold on the QSM
data.
PMID- 25131628
TI - Intravoxel incoherent motion diffusion-weighted imaging in head and neck squamous
cell carcinoma: assessment of perfusion-related parameters compared to dynamic
contrast-enhanced MRI.
AB - PURPOSE: To investigate the correlation between perfusion-related parameters
obtained with intravoxel incoherent motion (IVIM) and classical perfusion
parameters obtained with dynamic contrast-enhanced (DCE) magnetic resonance
imaging in patients with head and neck squamous cell carcinoma (HNSCC), and to
compare direct and asymptotic fitting, the pixel-by-pixel approach, and a region
of interest (ROI)-based approach respectively for IVIM parameter calculation.
MATERIALS AND METHODS: Seventeen patients with HNSCC were included in this
retrospective study. All magnetic resonance (MR) scanning was performed using a
3T MR unit. Acquisition of IVIM was performed using single-shot spin-echo echo
planar imaging with three orthogonal gradients with 12 b-values (0, 10, 20, 30,
50, 80, 100, 200, 400, 800, 1000, and 2000). Perfusion-related parameters of
perfusion fraction 'f' and the pseudo-diffusion coefficient 'D*' were calculated
from IVIM data by using least square fitting with the two fitting methods of
direct and asymptotic fitting, respectively. DCE perfusion was performed in a
total of 64 dynamic phases with a 3.2-s phase interval. The two-compartment
exchange model was used for the quantification of tumor blood volume (TBV) and
tumor blood flow (TBF). Each tumor was delineated with a polygonal ROI for the
calculation of f, f?D* performed using both the pixel-by-pixel approach and the
ROI-based approach. In the pixel-by-pixel approach, after fitting each pixel to
obtain f, f?D* maps, the mean value in the delineated ROI on these maps was
calculated. In the ROI-based approach, the mean value of signal intensity was
calculated within the ROI for each b-value in IVIM images, and then fitting was
performed using these values. Correlations between f in a total of four
combinations (direct or asymptotic fitting and pixel-by-pixel or ROI-based
approach) and TBV were respectively analyzed using Pearson's correlation
coefficients. Correlations between f?D* and TBF were also similarly analyzed.
RESULTS: In all combinations of f and TBV, f?D* and TBF, there was a significant
correlation. In the comparison of f and TBV, a moderate correlation was observed
only between f obtained by direct fitting with the pixel-by-pixel approach,
whereas a good correlation was observed in the comparisons using the other three
combinations. In the comparison of f?D* and TBF, a good correlation was observed
only with f?D* obtained by asymptotic fitting with the ROI-based approach. In
contrast, moderate correlations were observed in the comparisons using the other
three combinations. CONCLUSION: IVIM was found to be feasible for the analysis of
perfusion-related parameters in patients with HNSCC. Especially, the combination
of asymptotic fitting with the ROI-based approach was better correlated with DCE
perfusion.
PMID- 25131630
TI - Aligning 3D time-of-flight MRA datasets for quantitative longitudinal studies:
evaluation of rigid registration techniques.
AB - OBJECTIVE: 3D Time-of-flight (TOF) magnetic resonance angiography is commonly
used for vascular analyses. A quantification of longitudinal morphological
changes usually requires the registration of TOF image sequences acquired at
different time points. The aim of this study was to evaluate the precision of
different 3D rigid registration setups such that an optimal quantification of
morphological changes can be achieved. METHODS: Eight different rigid
registration techniques were implemented and evaluated in this study using the
target registration error (TRE) calculated based on 554 landmarks defined in
twenty TOF datasets. The registration techniques differed in integration of brain
and vessel segmentation masks and usage of a multi-resolution framework.
Furthermore, the benefit of a prior volume-of-interest definition for
registration accuracy was evaluated. RESULTS: The results revealed that the
highest registration accuracies can be achieved using a multi-resolution
framework and a cerebrovascular segmentation as mask. Numerically, a mean TRE of
1.1mm was calculated. If applicable, a prior definition of a volume-of-interest
allows a reduction of the TRE to only 0.6mm. CONCLUSION: TOF datasets should be
registered using vessel segmentations as mask, multi-resolution framework and
previous volume-of-interest definition if possible to obtain the highest
registration precision. This is especially the case for longitudinal datasets
that are separated by several months while the registration technique seems less
important for datasets that are only separated by a few days.
PMID- 25131629
TI - Delayed gadolinium-enhanced MRI of the fibrocartilage disc of the
temporomandibular joint--a feasibility study.
AB - OBJECTIVE: To 1) test the feasibility of delayed Gadolinium-Enhanced Magnetic
Resonance Imaging of Cartilage (dGEMRIC) at 3 T in the temporomandibular joint
(TMJ) and 2) to determine the optimal delay for measurements of the TMJ disc
after i.v. contrast agent (CA) administration. DESIGN: MRI of the right and left
TMJ of six asymptomatic volunteers was performed at 3 T using a dedicated coil.
2D inversion recovery (2D-IR) sequences were performed at 4 time points covering
120 minutes and 3D gradient-echo (3D GRE) dual flip-angle sequences were
performed at 14 time points covering 130 minutes after the administration of 0.2
mmol/kg of Gd-diethylenetriamine pentaacetic acid ion (Gd-DTPA)(2-), i.e., 0.4 mL
of MagnevistTM per kg body weight. Pair-wise tests were used to assess
differences between pre-and post-contrast T1 values. RESULTS: 2D-IR sequences
showed a statistically significant drop (p<0.001) in T1 values after i.v. CA
administration. The T1 drop of 50% was reached 60 minutes after bolus injection
in the TMJ disc. The 3D GRE dual flip-angle sequences confirmed these results and
show plateau of T1 after 60 minutes. CONCLUSIONS: T1(Gd) maps calculated from
dGEMRIC data allow in vivo assessment of the fibrocartilage disc of the TMJ. The
recommended measurement time for dGEMRIC in the TMJ after i.v. CA administration
is from 60 to 120 minutes.
PMID- 25131631
TI - Image registration guided, sparsity constrained reconstructions for dynamic MRI.
AB - It is generally a challenging task to reconstruct dynamic magnetic resonance (MR)
images with high spatial and high temporal resolutions, especially with highly
incomplete k-space sampling. In this work, a novel method that combines a non
rigid image registration technique with sparsity-constrained image reconstruction
is introduced. Employing a multi-resolution free-form deformation technique with
B-spline interpolations, the non-rigid image registration accurately models the
complex deformations of the physiological dynamics, and provides artifact
suppressed high spatial-resolution predictions. Based on these prediction images,
the sparsity-constrained data fidelity-enforced image reconstruction further
improves the reconstruction accuracy. When compared with the k-t FOCUSS with
motion estimation/motion compensation (MEMC) technique on volunteer scans, the
proposed method consistently outperforms in both the spatial and the temporal
accuracy with variously accelerated k-space sampling. High fidelity
reconstructions for dynamic systolic phases with reduction factor of 10 and
cardiac perfusion series with reduction factor of 3 are presented.
PMID- 25131632
TI - Synthesis of tetraphenylethylene pillar[6]arenes and the selective fast quenching
of their AIE fluorescence by TNT.
AB - Tetraphenylethylene pillar[6]arenes with an AIE effect were synthesized for the
first time. The fluorescence of the pillar[6]arenes could be quenched much more
and much faster by TNT than by other nitroaromatics including 2,4,6
trinitrophenol, which could be used to detect TNT in air.
PMID- 25131633
TI - Design of a Gd-DOTA-phthalocyanine conjugate combining MRI contrast imaging and
photosensitization properties as a potential molecular theranostic.
AB - The design and synthesis of a phthalocyanine--Gd-DOTA conjugate is presented to
open the way to novel molecular theranostics, combining the properties of MRI
contrast imaging with photodynamic therapy. The rational design of the conjugate
integrates isomeric purity of the phthalocyanine core substitution, suitable
biocompatibility with the use of polyoxo water-solubilizing substituents, and a
convergent synthetic strategy ended by the use of click chemistry to graft the Gd
DOTA moiety to the phthalocyanine. Photophysical and photochemical properties,
contrast imaging experiments and preliminary in vitro investigations proved that
such a combination is relevant and lead to a new type of potential theranostic
agent.
PMID- 25131635
TI - Text Mining Driven Drug-Drug Interaction Detection.
AB - Identifying drug-drug interactions is an important and challenging problem in
computational biology and healthcare research. There are accurate, structured but
limited domain knowledge and noisy, unstructured but abundant textual information
available for building predictive models. The difficulty lies in mining the true
patterns embedded in text data and developing efficient and effective ways to
combine heterogenous types of information. We demonstrate a novel approach of
leveraging augmented text-mining features to build a logistic regression model
with improved prediction performance (in terms of discrimination and
calibration). Our model based on synthesized features significantly outperforms
the model trained with only structured features (AUC: 96% vs. 91%, Sensitivity:
90% vs. 82% and Specificity: 88% vs. 81%). Along with the quantitative results,
we also show learned "latent topics", an intermediary result of our text mining
module, and discuss their implications.
PMID- 25131636
TI - Electrical conduction behavior of organic light-emitting diodes using fluorinated
self-assembled monolayer with molybdenum oxide-doped hole transporting layer.
AB - The electrical conductivity behavior of a fluorinated self-assembled monolayer
(FSAM) of a molybdenum oxide (MoOx)-doped alpha-naphthyl diamine derivative
(alpha-NPD) in organic light-emitting diodes (OLEDs) was investigated. The
current density of the MoOx-doped alpha-NPD/FSAM device was proportional to its
voltage owing to smooth carrier injection through the FSAM and the high carrier
density of its bulk. The temperature-dependent characteristics of this device
were investigated. The current density-voltage characteristics at different
temperatures were almost the same owing to its very low activation energy. The
activation energy of the device was estimated to be 1.056 * 10(-2) [eV] and was
very low due to the inelastic electron tunneling of FSAM molecules.
PMID- 25131634
TI - Expression profile analysis of vulnerable CA1 pyramidal neurons in young-Middle
Aged Ts65Dn mice.
AB - Down syndrome (DS) is the most prevalent cause of intellectual disability (ID).
Individuals with DS show a variety of cognitive deficits, most notably in
hippocampal learning and memory, and display pathological hallmarks of
Alzheimer's disease (AD), with neurodegeneration of cholinergic basal forebrain
(CBF) neurons. Elucidation of the molecular and cellular underpinnings of
neuropathology has been assessed via gene expression analysis in a relevant
animal model, termed the Ts65Dn mouse. The Ts65Dn mouse is a segmental trisomy
model of DS that mimics DS/AD pathology, notably age-related cognitive
dysfunction and degeneration of basal forebrain cholinergic neurons (BFCNs). To
determine expression level changes, molecular fingerprinting of cornu ammonis 1
(CA1) pyramidal neurons was performed in adult (4-9 month-old) Ts65Dn mice, at
the initiation of BFCN degeneration. To quantitate transcriptomic changes during
this early time period, laser capture microdissection (LCM), terminal
continuation (TC) RNA amplification, custom-designed microarray analysis, and
subsequent validation of individual transcripts by qPCR and protein analysis via
immunoblotting was performed. The results indicate significant alterations within
CA1 pyramidal neurons of Ts65Dn mice compared with normal disomic (2N)
littermates, notably in the downregulation of neurotrophins and their cognate
neurotrophin receptors among other classes of transcripts relevant to
neurodegeneration. The results of this single-population gene expression analysis
at the time of septohippocampal deficits in a trisomic mouse model shed light on
a vulnerable circuit that may cause the AD-like pathology invariably seen in DS
that could help to identify mechanisms of degeneration, and provide novel gene
targets for therapeutic interventions. J. Comp. Neurol. 523:61-74, 2015. (c) 2014
Wiley Periodicals, Inc.
PMID- 25131637
TI - Setting the stage for development of a program for adolescent heart transplant
recipients to transition to adult providers: An integrative review of the
literature.
AB - PURPOSE: This integrative review of the literature was undertaken to determine if
there was a body of knowledge to support a transition program in an adolescent
heart transplant population. CONCLUSIONS: No studies were found involving a heart
transplant transition program for adolescents. A literature review for transition
in other chronic illness areas was undertaken. Youth with chronic illness are
inadequately prepared to transfer to adult providers. Transition programs should
be developed. These programs should be tailored to suit individual needs. They
should teach disease knowledge and encourage participation in self-management
skills. Participation in a transition program improved patients' quality of life
and improved their knowledge about their disease. PRACTICE IMPLICATIONS: Nurses
are in a unique position with chronically ill adolescents to promote positive
behaviors at every interaction. Encouraging self-management behaviors will
support these youth as they prepare to become adults.
PMID- 25131638
TI - Gorlin syndrome (nevoid basal cell carcinoma syndrome): update and literature
review.
AB - Gorlin syndrome, also called nevoid basal cell carcinoma syndrome, is an
autosomal dominant neurocutaneous disease characterized by developmental
anomalies such as palmar pits and rib anomaly, and tumorigenesis such as
medulloblastoma and basal cell carcinoma. This syndrome is mainly caused by a
mutation of PTCH1, a human homologue of Drosophila patched, including frameshift,
missense, or nonsense mutations. Genotype-phenotype correlation has not been
established. PTCH1 is a member of hedgehog signaling, which is a highly conserved
pathway in vertebrates, composed of hedgehog, SMO, and GLI proteins as well as
PTCH1. Given that hedgehog signaling regulates cell growth and development,
disorder of this pathway gives rise to not only developmental anomalies but also
diverse tumors such as those seen in Gorlin syndrome. We recently reported, for
the first time, a nationwide survey of Gorlin syndrome in Japan, noting that the
frequency was 1/235,800 in the Japanese population, and that the frequency of
basal cell carcinomas was significantly lower in Japan than in the USA and
Europe, suggesting that ethnicity and genetic background contribute to these
differences. Given that many clinical trials using newly discovered molecular
inhibitors are still ongoing, these agents should become the new therapeutic
options for hedgehog pathway-dependent tumors in patients with or without Gorlin
syndrome.
PMID- 25131639
TI - Dark macules in the upper gastrointestinal tract: an ominous sign.
PMID- 25131641
TI - 'Not-so-minor' stroke: Lasting psychosocial consequences of anterior cingulate
cortical ischemia in the rat.
AB - Patients with small, non-debilitating strokes often report a reduction in quality
of life due to persistent cognitive and emotional alterations. Stroke may
directly damage limbic circuitry resulting in an impaired stress response,
however the possibility that this may in part explain the prevalence of stroke
comorbidity with mood disorders has yet to be determined. Here we systematically
examine psychosocial consequences of prefrontal lesions targeting the left
anterior cingulate cortex (ACC) using hormone assays and a behavioral test
battery in adult rats to probe whether a small stroke could alter stress behavior
or response to psychosocial stress (chronic mild stress (CMS) or subordination
stress). Minor stroke produced chronic hyperactivity in an open field but did not
alter fear-related inhibition in the elevated plus maze. Novelty-induced
defecation was increased by the combination of CMS, subordination and stroke.
Anterior cingulate lesions alone increased distress vocalizations in the water
maze. Interestingly, ACC stroke caused hyper-secretion of porphyrin and long-term
hormonal alterations that resulted in adrenal hypertrophy and enhanced
dexamethasone suppression of the HPA axis. We propose that this behavioral
profile is consistent with an animal model of post-stroke distress-like syndrome
which could be useful in understanding how stroke affects the capacity to cope
with psychological stress.
PMID- 25131642
TI - International Classification of Functioning, Disability and Health Core Sets for
children and youth with cerebral palsy: a consensus meeting.
AB - AIM: The objective of this article is to report on the Core Sets developed for
children and youth aged 0 to 18 years, with cerebral palsy (CP) based on the
pediatric International Classification of Functioning, Disability and Health
(ICF) by the World Health Organization (WHO). METHOD: A formal decision-making
and consensus process integrating evidence gathered from preparatory studies was
followed. Preparatory studies included: a systematic literature review; an
international expert survey; a qualitative study of children and youth with CP
and their caregivers; and a clinical study. Relevant ICF categories were
identified in a formal consensus process by international experts from different
backgrounds. Twenty-six international experts chosen by WHO region with expertise
in CP attended the consensus meeting. RESULTS: Overall, five ICF Core Sets were
developed: a Comprehensive Core Set (135 ICF categories); a Common Brief (25 ICF
categories); and three age-specific Core Sets: under 6 years (31 ICF categories),
from 6 to <14 years (35 ICF categories) and from 14 to 18 years (37 ICF
categories). INTERPRETATION: These ICF Core Sets for children and youth with CP
are the first ICF-based tools developed for this population. The ICF Core Sets
for children and youth with CP can be applied in clinical practice, research,
teaching and administration. The application of the ICF Core Sets to this
population will standardize the functional assessments of CP worldwide.
PMID- 25131640
TI - Epigenetics and sex differences in the brain: A genome-wide comparison of histone
3 lysine-4 trimethylation (H3K4me3) in male and female mice.
AB - Many neurological and psychiatric disorders exhibit gender disparities, and sex
differences in the brain likely explain some of these effects. Recent work in
rodents points to a role for epigenetics in the development or maintenance of
neural sex differences, although genome-wide studies have so far been lacking.
Here we review the existing literature on epigenetics and brain sexual
differentiation and present preliminary analyses on the genome-wide distribution
of histone-3 lysine-4 trimethylation in a sexually dimorphic brain region in male
and female mice. H3K4me3 is a histone mark primarily organized as 'peaks'
surrounding the transcription start site of active genes. We microdissected the
bed nucleus of the stria terminalis and preoptic area (BNST/POA) in adult male
and female mice and used ChIP-Seq to compare the distribution of H3K4me3
throughout the genome. We found 248 genes and loci with a significant sex
difference in H3K4me3. Of these, the majority (71%) had larger H3K4me3 peaks in
females. Comparisons with existing databases indicate that genes and loci with
increased H3K4me3 in females are associated with synaptic function and with
expression atlases from related brain areas. Based on RT-PCR, only a minority of
genes with a sex difference in H3K4me3 has detectable sex differences in
expression at baseline conditions. Together with previous findings, our data
suggest that there may be sex biases in the use of epigenetic marks. Such biases
could underlie sex differences in vulnerabilities to drugs or diseases that
disrupt specific epigenetic processes.
PMID- 25131643
TI - Systematic review of epilepsy self-management interventions integrated with a
synthesis of children and young people's views and experiences.
AB - AIM: To determine the effectiveness of epilepsy self-management interventions and
explore the views and experiences of medication and seizures by children and
young people. BACKGROUND: Experiencing seizures and side-effects from anti
epileptic medicines have negative impacts on children and young people managing
their epilepsy. Children commonly experiment with not taking epilepsy medication
as prescribed and engage in unhealthy lifestyles. DESIGN/REVIEW METHODS: Mixed
method systematic review with theory development. Cochrane quantitative methods
and thematic synthesis of qualitative and survey evidence. DATA SOURCES: Eight
databases were searched from earliest dates to July 2013. RESULTS: Nineteen
studies were included. Meta-analysis was not possible. Zero of nine intervention
studies showed improvement in anti-epilepsy medication adherence. Skill-based
behavioural techniques with activities such as role play and goal setting with
young people increased epilepsy knowledge and seizure self-management (small
effects). Intervention studies were methodologically weak and no studies reported
if improvement in self-management was sustained over time. Synthesis of nine
qualitative and one mixed-method studies generated six themes encapsulating anti
epilepsy medication and epilepsy effects. There was a lack of fidelity between
intervention programme theories and what children and young people found
difficult with medication self-management and managing the effects of epilepsy.
CONCLUSION: Children and young people knowingly and/or unknowingly take risks
with their epilepsy and give reasoned explanations for doing so. There are no
effective interventions to change epilepsy medication adherence behaviours. There
is an urgent need for more innovative and individually tailored interventions to
address specific challenges to epilepsy self-management as identified by children
and young people themselves.
PMID- 25131644
TI - Surgical repositioning of a developing maxillary central incisor. A case report.
AB - BACKGROUND: A traumatic injury to the primary dentition can cause damage to the
germ of the permanent successor. As a clinical consequence a dilaceration with
root deformation, malpositioning and disturbances of eruption can occur. Surgical
repositioning of such a dislocated crown of a developing tooth can be a treatment
option. CASE REPORT: A four year old patient was referred to our clinic because
of a mobile upper primary central incisor and a radiographically visible
displaced dental crown. Her history revealed a traumatic dental injury one year
ago. Radiologic examination confirmed an inflammatory root resorption on tooth 61
and a dislocation of the developing tooth 21. In order to avoid further
displacement due to the inflammation, 61 was extracted at the first appointment.
A radiographic image 7 months later showed no improvement in the malposition of
tooth 21. Therefore tooth 21 was surgically repositioned into its correct
position. Follow-up over 3 years confirmed a continued root development and a
full eruption of 21 in its correct position. CONCLUSION: Early diagnosis and
early treatment of a dislocated permanent tooth germ is essential to allow a
favorable outcome. Surgical repositioning can be successful in avoiding later
malpositioning of the permanent teeth.
PMID- 25131645
TI - Declining trends in the proportion of non-viral sexually transmissible infections
reported by STD clinics in the US, 2000-10.
AB - Background Recent budget shortfalls may have resulted in decreases in the number
of sexually transmissible infections (STIs) reported from sexually transmitted
disease clinics (STDCs) in the United States (US). The objective of this study
was to examine the proportion of cases reported from STDCs for three non-viral
STIs in the last decade. METHODS: Data from the national surveillance database on
primary and secondary (P&S) syphilis, gonorrhoea and chlamydia cases for 2000-10
were extracted. The percentage of cases reported by STDCs for the nation and for
each of the 48 contiguous states were then computed. Finally, the chi(2) trend
test for proportions was used to determine the annual average decrease/increase
in the percentage of cases reported by STDCs for the nation and for each state.
RESULTS: RESULTS demonstrate that the average annual declines in the proportion
of P&S syphilis, gonorrhoea, and chlamydia cases reported from STDCs were 1.43%
(P<0.01), 1.31% (P<0.01), and 0.31% (P<0.01), respectively. Additionally, most of
the states with statistically significant trends (P<0.05) in the proportion of
cases reported by STDCs had negative slopes: 86% (25/29) for P&S syphilis, 89%
(34/38) for gonorrhoea, and 63% (27/43) for chlamydia. CONCLUSION: These results
document the declining role of STDCs in STI prevention and control efforts in the
US. Further studies are needed to assess the direct or indirect impact of the
decline in the proportion of cases from STDCs on the overall STI control and
prevention efforts in the US and its implications for the future.
PMID- 25131646
TI - Enzymatic routes for the synthesis of ursodeoxycholic acid.
AB - Ursodeoxycholic acid, a secondary bile acid, is used as a drug for the treatment
of various liver diseases, the optimal dose comprises the range of 8-10mg/kg/day.
For industrial syntheses, the structural complexity of this bile acid requires
the use of an appropriate starting material as well as the application of regio-
and enantio-selective enzymes for its derivatization. Most strategies for the
synthesis start from cholic acid or chenodeoxycholic acid. The latter requires
the conversion of the hydroxyl group at C-7 from alpha- into beta-position in
order to obtain ursodeoxycholic acid. Cholic acid on the other hand does not only
require the same epimerization reaction at C-7 but the removal of the hydroxyl
group at C-12 as well. There are several bacterial regio- and enantio-selective
hydroxysteroid dehydrogenases (HSDHs) to carry out the desired reactions, for
example 7alpha-HSDHs from strains of Clostridium, Bacteroides or Xanthomonas,
7beta-HSDHs from Clostridium, Collinsella, or Ruminococcus, or 12alpha-HSDH from
Clostridium or from Eggerthella. However, all these bioconversion reactions need
additional steps for the regeneration of the coenzymes. Selected multi-step
reaction systems for the synthesis of ursodeoxycholic acid are presented in this
review.
PMID- 25131647
TI - Hepatitis C virus: the 25-year journey from discovery to cure.
PMID- 25131648
TI - Identity, causality, and pronoun ambiguity.
AB - This article looks at the way people determine the antecedent of a pronoun in
sentence pairs, such as: Albert invited Ron to dinner. He spent hours cleaning
the house. The experiment reported here is motivated by the idea that such
judgments depend on reasoning about identity (e.g., the identity of the he who
cleaned the house). Because the identity of an individual over time depends on
the causal-historical path connecting the stages of the individual, the correct
antecedent will also depend on causal connections. The experiment varied how
likely it is that the event of the first sentence (e.g., the invitation) would
cause the event of the second (the house cleaning) for each of the two
individuals (the likelihood that if Albert invited Ron to dinner, this would
cause Albert to clean the house, versus cause Ron to clean the house). Decisions
about the antecedent followed causal likelihood. A mathematical model of causal
identity accounted for most of the key aspects of the data from the individual
sentence pairs.
PMID- 25131649
TI - Variation of system performance, quality control standards and adherence to
international FDG-PET/CT imaging guidelines. A national survey of PET/CT
operations in Austria.
AB - AIM: To gather information on clinical operations, quality control (QC) standards
and adoption of guidelines for FDG-PET/CT imaging in Austrian PET/CT centres.
METHODS: A written survey composed of 68 questions related to A) PET/CT centre
and installation, B) standard protocol parameters for FDG-PET/CT imaging of
oncology patients, and C) standard QC procedures was conducted between November
and December 2013 among all Austrian PET/CT centres. In addition, a NEMA-NU2 2012
image quality phantom test was performed using standard whole-body imaging
settings on all PET/CT systems with a lesion-to-background ratio of 4. Recovery
coefficients (RC) were calculated for each lesion and PET/CT system. RESULTS: A)
13 PET/CT systems were installed in 12 nuclear medicine departments at public
hospitals. B) Average fasting prior to FDG-PET/CT was 7.6 (4-12) h. All sites
measured blood glucose levels while using different cut-off levels (64%: 150
mg/dl). Weight-based activity injection was performed at 83% sites with a mean
FDG activity of 4.1 MBq/kg. Average FDG uptake time was 55 (45-75) min. All sites
employed CT contrast agents (variation from 1%-95% of the patients). All sites
reported SUV-max. C) Frequency of QC tests varied significantly and QC phantom
measurements revealed significant differences in RCs. CONCLUSION: Significant
variations in FDG-PET/CT protocol parameters among all Austrian PET/CT users were
observed. Subsequently, efforts need to be put in place to further standardize
imaging protocols. At a minimum clinical PET/CT operations should ensure
compliance with existing guidelines. Further, standardized QC procedures must be
followed to improve quantitative accuracy across PET/CT centres.
PMID- 25131650
TI - Weight maintenance from young adult weight predicts better health outcomes.
AB - OBJECTIVE: Defining groups of individuals within a larger population with similar
patterns of weight change over time may provide insight into influences of weight
stability or gain. METHODS: Latent class growth modeling was used to define
subgroups of weight change in adult members of the Gila River Indian Community
participating in at least four non-diabetic health exams including OGTTs (N =
1,157, 762F/395M; 78.4 +/- 19.0 kg). In a separate study, 152 individuals had 24
h EE measured in a respiratory chamber. RESULTS: Eight groups with baseline
weights of 54.6 +/- 7.3 (n = 124), 64.2 +/- 7.7 (n = 267), 73.6 +/- 7.8 (n =
298), 86.1 +/- 10.2 (n = 194), 95.5 +/- 6.7 (n = 90), 97.9 +/- 10.4 (n = 92),
110.9 +/- 11.9 (n = 61), and 122.1 +/- 13.6 (n = 31) kg (P < 0.001) were
delineated. Group 5, (initial weight = 95.5 +/- 6.7 kg) maintained a
comparatively stable weight over time (+3.3 +/- 10.3 kg, +3.8 +/- 11.2% of
initial weight; median follow-up time: 13.1 years). All other groups gained
weight over time (+29.9 +/- 21.1% of initial weight; median follow-up time: 16.3
years). Higher starting weight defined weight gain in most groups, but higher 2 h
glucose predicted membership in the lower weight trajectories. The weight stable
group had higher rates of impaired glucose regulation at baseline and higher 24-h
EE. CONCLUSIONS: Weight in young adulthood defined weight gain trajectory
underscoring the importance of intervening early to prevent weight gain.
PMID- 25131651
TI - Fungal diversity, incidence and mycotoxin contamination in grapes from two agro
climatic Spanish regions with emphasis on Aspergillus species.
AB - BACKGROUND: Fourteen vineyards from two different agro-climatic regions in Spain
were sampled in two consecutive years in order to determinate the grape mycobiota
and diversity indexes with the final aim to define the potential mycotoxigenic
species from both regions and their relationship. RESULTS: The most common fungal
genera encountered were Aspergillus (30.0%), Alternaria (53.2%), Cladosporium
(11.9%) and Penicillium (2.9%). Black aspergilli presence in the hotter region
(south) was significantly higher (P < 0.05) than in the northeast in both years.
Among black aspergilli, A. tubingensis seemed to be the better adapted species to
environmental conditions, while A. carbonarius was the main potentially
ochratoxigenic species in both regions and years, owing to the most relevant
percentage of ochratoxigenic isolates. Ochratoxin A (OTA)-positive musts were
only detected from southern vineyards, although contamination was always lower
than 0.1 ug L(-1) . Finally, none of black aspergilli tested produced fumonisins
(FBs) on Czapek yeast extract agar (CYA), while 63% of A. niger tested produced
FB2 when inoculated on CYA20S, reaching 100% of isolates from the south.
CONCLUSION: Climate change scenarios in southern Europe point to an increase in
temperature and drought. This could promote particularly adapted species such as
A. niger, decreasing OTA risk, but this could lead to an increase in FB2
presence.
PMID- 25131652
TI - Free-breathing multislice native myocardial T1 mapping using the slice
interleaved T1 (STONE) sequence.
AB - PURPOSE: To develop a novel pulse sequence for free-breathing, multislice, native
myocardial T1 mapping. METHODS: The slice-interleaved T1 (STONE) sequence
consists of multiple sets of single-shot images of different slices, acquired
after a single nonselective inversion pulse. Each slice is only selectively
excited once after each inversion pulse to allow sampling of the unperturbed
longitudinal magnetization in the adjacent slices. For respiratory motion, a
prospective slice-tracking respiratory navigator is used to decrease through
plane motion followed by a retrospective image registration to reduce in-plane
motion. STONE T1 maps were calculated using both a two-parameter and three
parameter fit model. The accuracy and precision of the STONE sequence for
different T1 , T2 , and inversion pulse efficiency were studied using numerical
simulations and phantom experiments. T1 maps from 14 subjects were acquired with
the STONE sequence and T1 s were compared to the MOdified Look-Locker Inversion
recovery sequence (MOLLI). RESULTS: In numerical simulations and phantom
experiments, the STONE sequence using a two-parameter fit model yields more
accurate T1 times compared to MOLLI, with similar high precision. The three
parameter fit model further improves the accuracy, but with a reduced precision.
The native myocardial T1 times were higher in the STONE sequence using two- or
three-parameter fit compared to MOLLI. The standard deviation of the T1 times was
lower in the STONE T1 maps with a two-parameter fit compared with MOLLI or a
three-parameter fit. CONCLUSION: The STONE sequence allows accurate and precise
quantification of native myocardial T1 times with the additional benefit of
covering the entire ventricle. Magn Reson Med 74:115-124, 2015. (c) 2014 Wiley
Periodicals, Inc.
PMID- 25131653
TI - Investigating the role of social-affective attachment processes in cradling bias:
the absence of cradling bias in children with Autism Spectrum Disorders.
AB - Previous studies suggest that leftward cradling bias may facilitate mother-infant
relationships, as it preferentially locates the infant in the mother's left hemi
space, which is specialized for several social-affective processes. If leftward
cradling bias is mediated by social-affective attachment processes, it should be
reduced in humans who are deficient in such processes. Individuals diagnosed with
Autism Spectrum Disorders (ASDs) constitute a population with known deficits in
social and emotional relating. A pilot study confirmed reduced bias in this
group, and in the present study, we elaborated methods to assess also the impact
of higher cognitive processes on cradling bias. Direct systematic observation was
used to investigate the occurrence of cradling bias in ASD, non-ASD
intellectually disabled children and typically developing children. Ninety-three
participants aged 5-15 years cradled a life-like doll on four separate occasions.
Intelligence and executive functions were assessed. Regression analyses revealed
that ASD diagnosis was the only significant predictor of atypical cradling
preference. While intellectually disabled and typically developing children
clearly preferred to cradle to the left, no preference was evident in the ASD
group. Results support the hypothesis that leftward cradling bias is associated
with basic social-affective capacities.
PMID- 25131654
TI - Bortezomib for effective treatment of a child with refractory autoimmune
hemolytic anemia post allogeneic hematopoietic stem cell transplant.
PMID- 25131655
TI - Membrane pathology and microglial activation of mice expressing membrane anchored
or membrane released forms of Abeta and mutated human Alzheimer's precursor
protein (APP).
AB - AIMS: Alzheimer's disease and the transmissible spongiform encephalopathies or
prion diseases accumulate misfolded and aggregated forms of neuronal cell
membrane proteins. Distinctive membrane lesions caused by the accumulation of
disease-associated prion protein (PrP(d)) are found in prion disease but
morphological changes of membranes are not associated with Abeta in Alzheimer's
disease. Membrane changes occur in all prion diseases where PrP(d) is attached to
cell membranes by a glycosyl-phosphoinositol (GPI) anchor but are absent from
transgenic mice expressing anchorless PrP(d). Here we investigate whether GPI
membrane attached Abeta may also cause prion-like membrane lesions. METHODS: We
used immunogold electron microscopy to determine the localization and pathology
of Abeta accumulation in groups of transgenic mice expressing anchored or
unanchored forms of Abeta or mutated human Alzheimer's precursor protein.
RESULTS: GPI attached Abeta did not replicate the membrane lesions of PrP(d).
However, as with PrP(d) in prion disease, Abeta peptides derived from each
transgenic mouse line initially accumulated on morphologically normal neurite
membranes, elicited rapid glial recognition and neurite Abeta was transferred to
attenuated microglial and astrocytic processes. CONCLUSIONS: GPI attachment of
misfolded membrane proteins is insufficient to cause prion-like membrane lesions.
Prion disease and murine Abeta amyloidosis both accumulate misfolded monomeric or
oligomeric membrane proteins that are recognized by glial processes and acquire
such misfolded proteins prior to their accumulation in the extracellular space.
In contrast to prion disease where glial cells efficiently endocytose PrP(d) to
endolysosomes, activated microglial cells in murine Abeta amyloidosis are not as
efficient phagocytes.
PMID- 25131657
TI - Non-statistical key issues in conducting sensible observational studies to
resolve clinical questions.
PMID- 25131656
TI - DNA methylation aberrations rather than polymorphisms of FZD3 gene increase the
risk of spina bifida in a high-risk region for neural tube defects.
AB - BACKGROUND: Animal models of neural tube defects (NTDs) have indicated roles for
the Fzd3 gene and the planar cell polarity signaling pathway in convergent
extension. We investigated the involvement of FZD3 in genetic and epigenetic
mechanisms associated with human NTDs, especially spina bifida. We explored the
effects of variants spanning the FZD3 gene in NTDs and examined the role of
aberrant methylation of the FZD3 promoter on gene expression in brain tissue in
spina bifida. METHODS: Six FZD3 single nucleotide polymorphisms were genotyped
using a MassARRAY system in tissue from 165 NTD fetuses and 152 controls. DNA
methylation aberrations in the FZD3 promoter region were detected using a
MassARRAY EpiTYPER (17 CpG units from -500 to -2400 bp from the transcription
start site) in brain tissue from 77 spina bifida and 74 control fetuses. RESULTS:
None of the six single nucleotide polymorphisms evaluated were significantly
associated with spina bifida, but the mean methylation level was significantly
higher in spina bifida samples (13.70%) compared with control samples (10.91%) (p
= 0.001). In terms of specific sites, DNA methylation levels were significantly
higher in the spina bifida samples at 14 of the 17 CpG units, which mostly
included in R2 region. FZD3 mRNA expression was negatively correlated with
methylation of the FZD3 promoter region, especially the R2 region (R = 0.970; p =
0.001) in HeLa cells. CONCLUSION: The results of this study suggest that DNA
methylation plays an important role in FZD3 gene expression regulation and may be
associated with an increased risk of spina bifida.
PMID- 25131658
TI - Factors associated with receiving treatment for dental decay among Medicaid
enrolled children younger than 12 years of age in Iowa, 2010.
AB - OBJECTIVES: The Iowa Department of Public Health I-Smile program provides dental
screening and care coordination to over 23,000 low-income and Medicaid-enrolled
children per year. The purposes of this study were to evaluate I-Smile program
effectiveness to ensure that Medicaid-enrolled children obtained dental treatment
after having been screened and to determine the factors associated with failure
to receive dental care after screening through the I-Smile program. METHODS:
Based on I-Smile program priorities, we limited our sample to children younger
than 12 years of age who screened positive for decay and who linked to a paid
Medicaid claim for dental treatment (n = 1,816). We conducted bivariate analyses
to examine associations between children's characteristics who screened positive
for decay and received treatment within 6 months of their initial screening. We
also performed multivariate logistic regression to assess the association of
sociodemographic characteristics with receipt of treatment among children who
screened positive for decay. RESULTS: Eleven percent of children screened
positive for decay. Nearly 24 percent of children with decay received treatment
based on a Medicaid-paid claim. Being 5 years or older [adjusted odds ratio
(aOR): 1.48, confidence interval (CI): 1.17, 1.88] and not having a dental home
(aOR: 1.90, CI: 1.41, 2.58) were associated with higher odds of not receiving
dental treatment. CONCLUSIONS: Children 5 years and older and without a dental
home were less likely to obtain dental treatment. Opportunities exist for the I
Smile program to increase the numbers of at-risk children with dental homes and
who obtain dental care after screening.
PMID- 25131659
TI - MALDI imaging-based identification of prognostically relevant signals in bladder
cancer using large-scale tissue microarrays.
AB - OBJECTIVE: Although most patients with urinary bladder cancer present with
noninvasive and low-malignant stages of the disease, about 20% eventually develop
life-threatening metastatic tumors. This study was designed to evaluate the
potential of matrix-assisted laser desorption/ionization (MALDI) mass
spectrometry imaging (MSI) to identify molecular markers predicting the clinical
course of bladder cancer. MATERIALS AND METHODS: We employed MALDI-MSI to a
bladder cancer tissue microarray including paraffin-embedded tissue samples from
697 patients with clinical follow-up data to search for prognostically relevant
associations. RESULTS: Analysis of our MALDI imaging data revealed 40 signals in
the mass spectra (m/z signals) associated with epithelial structures. The
presence of numerous m/z signals was statistically related to one or several
phenotypical findings including tumor aggressiveness (stage, grade, or nodal
status; 30 signals), solid (5 signals) or papillary (3 signals) growth patterns,
and increased (6 signals) or decreased (12 signals) cell proliferation, as
determined by Ki-67 immunohistochemistry. Two signals were linked with tumor
recurrence in noninvasive (pTa category) tumors, of which one was also related to
progression from pTa-category to pT1-category disease. The absence of one m/z
signal was linked with decreased survival in the subset of 102 muscle-invasive
cancers. CONCLUSION: Our data demonstrate the suitability of combining MSI and
large-scale tissue microarrays to simultaneously identify and validate clinically
useful molecular markers in urinary bladder cancer.
PMID- 25131662
TI - 3D reconstruction of prior beta grains in friction stir-processed Ti-6Al-4V.
AB - The prior beta grain structure and orientations in the central stir zone of
friction stir-processed Ti-6Al-4V were reconstructed from measured alpha phase
orientations obtained by three-dimensional serial sectioning in a dual-beam
focused ion beam scanning electron microscope. The data were processed to obtain
the alpha colony and beta grain size distributions in the volume. Several beta
grains were individually analysed to determine the total number of unique alpha
variants and the respective volume fractions of each. The analysis revealed that
some grains experienced overwhelming variant selection (i.e. one variant
dominated) whereas other beta grains contained a more evenly distributed mixture
of all 12 variants.
PMID- 25131660
TI - Can we expand active surveillance criteria to include biopsy Gleason 3+4 prostate
cancer? A multi-institutional study of 2,323 patients.
AB - OBJECTIVE: To test the expandability of active surveillance (AS) to Gleason score
3+4 cancers by assessing the unfavorable disease risk in a large multi
institutional cohort. MATERIALS AND METHODS: We performed a retrospective
analysis including 2,323 patients with localized Gleason score 3+4 prostate
cancer who underwent a radical prostatectomy between 2005 and 2013 from 6
academic centers. We analyzed the rates of biopsy downgrading/upgrading and
advanced stage in the overall cohort by employing standardized AS criteria (using
biopsy Gleason score 3+4). RESULTS: The final pathologic Gleason score was 3+3 =
6 in 8%, 3+4 = 7 in 67%, 4+3 = 7 in 20%, and 8 to 10 in 5% cases. The overall
rate of unfavorable disease (upgrading or advanced stage or both) was 46%. In
multivariable analysis, prostate-specific antigen (PSA) level>10 ng/ml, PSA
density (PSAD) >0.15 ng/ml/g, clinical stage >T1, and>2 positive cores were
predictors of unfavorable disease. According to the AS criteria used, the risk of
unfavorable disease ranged from 30% to 42%. In patients without any risk factor
(PSA level<= 10 ng/ml, PSAD <= 0.15 ng/ml/g, T1c, and <= 2 positive cores), the
unfavorable disease rate was 19%. The main limitations of this study are the
retrospective design and nonstandardization of pathologic assessment between
centers. CONCLUSIONS: Approximately half of patients with biopsy Gleason score
3+4 cancer have unfavorable disease at final pathology. Nevertheless, expanding
AS eligibility to these patients may be acceptable provided adherence to strict
selection criteria leading to a<20% risk of unfavorable disease. Future tools for
selection such as magnetic resonance imaging, early rebiopsy, and serum markers
may be especially beneficial in this group of patients.
PMID- 25131663
TI - Catheter ablation for cold water swallowing-induced paroxysmal atrial
fibrillation: a case report.
PMID- 25131661
TI - Behavior change techniques implemented in electronic lifestyle activity monitors:
a systematic content analysis.
AB - BACKGROUND: Electronic activity monitors (such as those manufactured by Fitbit,
Jawbone, and Nike) improve on standard pedometers by providing automated feedback
and interactive behavior change tools via mobile device or personal computer.
These monitors are commercially popular and show promise for use in public health
interventions. However, little is known about the content of their feedback
applications and how individual monitors may differ from one another. OBJECTIVE:
The purpose of this study was to describe the behavior change techniques
implemented in commercially available electronic activity monitors. METHODS:
Electronic activity monitors (N=13) were systematically identified and tested by
3 trained coders for at least 1 week each. All monitors measured lifestyle
physical activity and provided feedback via an app (computer or mobile). Coding
was based on a hierarchical list of 93 behavior change techniques. Further coding
of potentially effective techniques and adherence to theory-based recommendations
were based on findings from meta-analyses and meta-regressions in the research
literature. RESULTS: All monitors provided tools for self-monitoring, feedback,
and environmental change by definition. The next most prevalent techniques (13
out of 13 monitors) were goal-setting and emphasizing discrepancy between current
and goal behavior. Review of behavioral goals, social support, social comparison,
prompts/cues, rewards, and a focus on past success were found in more than half
of the systems. The monitors included a range of 5-10 of 14 total techniques
identified from the research literature as potentially effective. Most of the
monitors included goal-setting, self-monitoring, and feedback content that
closely matched recommendations from social cognitive theory. CONCLUSIONS:
Electronic activity monitors contain a wide range of behavior change techniques
typically used in clinical behavioral interventions. Thus, the monitors may
represent a medium by which these interventions could be translated for
widespread use. This technology has broad applications for use in clinical,
public health, and rehabilitation settings.
PMID- 25131664
TI - Circadian pattern of fibrillatory events in non-Brugada-type idiopathic
ventricular fibrillation with a focus on J waves.
AB - BACKGROUND: The circadian pattern of ventricular fibrillation (VF) episodes in
patients with idiopathic ventricular fibrillation (IVF) is poorly understood.
OBJECTIVE: The purpose of this study was to assess the circadian pattern of VF
occurrence in patients with IVF. METHODS: Excluding Brugada syndrome and other
primary electrical diseases, the circadian pattern of VF occurrence was
determined in 64 patients with IVF. The clinical and electrocardiographic
characteristics were compared among patients with nocturnal (midnight to 6:00 AM)
VF and nonnocturnal VF in relation to J waves. A J wave was defined as either
notching or a slur at the QRS terminal >0.1 mV above the isoelectric line in
contiguous leads. RESULTS: The overall distribution pattern of VF occurrence
showed 2 peaks at approximately 6:00 AM and around 8:00 PM. Nocturnal VF was
observed in 20 patients (31.3%), and J waves were present in 14 of these 20
individuals (70.0%), whereas J waves were less frequent in the 44 nonnocturnal
patients with VF: 16 (36.4%) (P = .0117). Among patients with J waves, nocturnal
VF was observed in 46.7% with a peak at approximately 4:00 AM. Nocturnal VF was
less common in patients without J waves, occurring in only 17.6% (P = .0124).
Both the type and location of J waves and the pattern of the ST segment were
similar between the nocturnal and nonnocturnal VF groups. J waves were associated
with a VF storm and long-term arrhythmia recurrence. CONCLUSION: In IVF, the
presence of J waves may characterize a higher nocturnal incidence of VF and a
higher acute and chronic risk of recurrence.
PMID- 25131665
TI - Prospective long-term evaluation of Optim-insulated (Riata ST Optim and Durata)
implantable cardioverter-defibrillator leads.
AB - BACKGROUND: St Jude Medical Optim-insulated implantable cardioverter
defibrillator leads were designed to impart lubricity, strength, and abrasion
resistance while maintaining flexibility and biostability. No long-term
prospective follow-up data have been published. OBJECTIVE: The objective of this
study was to determine the rates of all-cause mechanical failure and its subtypes
(conductor fracture, insulation abrasion, externalized conductors, and other
mechanical failures) in a prospective cohort of Optim-insulated implantable
cardioverter-defibrillator leads. METHODS: St Jude Medical established 3
prospective registries and enrolled 11,016 leads implanted in 10,835 patients
beginning in 2006. There was standardized baseline documentation, 6-monthly
follow-up, adverse events reports (verified by expert staff using detailed
algorithms), and documentation of lead revisions or inactivation, study
withdrawal, and death. The Population Health Research Institute (McMaster
University) was engaged to review database functions, adjudicate all potential
mechanical lead failures, and conduct independent analyses of the data. RESULTS:
During a median follow-up of 3.2 years, there were 51 mechanical failures
(0.46%), with 99.0% survival free of this outcome by 5 years of follow-up.
Freedom from conductor fracture was identified in 99.4% and from all-cause
abrasion in 99.8% of the leads, and there were no reports of externalized
conductors. There were no significant differences in survival among Durata DF4,
Durata DF1, and Riata ST Optim leads. CONCLUSION: Over a mean follow-up of 3.2
years, Optim-insulated leads have low rates of all-cause mechanical failure and
no observed externalized conductors. Independent analyses of these registries are
designed to provide reliable long-term follow-up information and are ongoing.
PMID- 25131666
TI - Clinical and procedural predictors of early complications of ablation for atrial
fibrillation: analysis of the national registry data.
AB - BACKGROUND: The risk assessment of the complication from atrial fibrillation (AF)
ablation is important and needs to be updated. OBJECTIVE: The purpose of this
study was to investigate the clinical and procedural factors associated with AF
ablation-related early complications. METHODS: The Japanese Heart Rhythm Society
invited electrophysiology centers in Japan to register data regarding all AF
ablation procedures performed in September 2011, March 2012, and September 2012.
Of the 46 putative predictors assessed in the univariate analysis, significant
variables (P < .1) were entered into a stepwise logistic regression model for
multivariate analysis. RESULTS: Data for 3373 cases were submitted by 165
centers, with 158 early complications reported in 151 patients (4.5%). We
identified 13 significant variables in the univariate analysis. Multivariate
analysis revealed that 8 (62%) of them were independent predictors of early
complications. Female sex (odds ratio and 95% confidence interval 1.6; 1.13
2.27), hypertrophic cardiomyopathy (2.2; 1.08-4.5), valvular heart disease (2.53;
1.28-5.05), deep sedation during the procedure (1.53; 1.09-2.12), and complex
fractionated atrial electrocardiogram ablation (1.88; 1.23-2.87) increased early
complications. Preprocedural transesophageal echocardiography (0.63; 0.43-0.92),
irrigated-tip catheter use (0.46; 0.3-0.69), and periprocedural novel oral
anticoagulant use (0.55; 0.32-0.97) decreased them. CONCLUSION: The risk of early
complications is increased by female sex, hypertrophic cardiomyopathy, valvular
heart disease, deep sedation, and complex fractionated atrial electrocardiogram
ablation. It is decreased by preprocedural transesophageal echocardiography,
periprocedural novel oral anticoagulant, and irrigated-tip catheter use.
PMID- 25131667
TI - Newly detected atrial high rate episodes predict long-term mortality outcomes in
patients with permanent pacemakers.
AB - BACKGROUND: Subclinical atrial high rate episodes (AHREs) detected by implanted
devices in patients with no history of atrial fibrillation (AF) have been
associated with an increased risk of stroke and systemic embolism. Data regarding
the long-term survival of patients with permanent pacemakers and newly detected
AHREs are limited. OBJECTIVE: This study aimed to assess whether newly detected
AHREs in pacemaker patients predict mortality outcomes. METHODS: We evaluated 224
patients (mean age 74 +/- 12 years; 118 men [53%]) with no history of AF who
underwent dual-chamber pacemaker implantation from 2002 through 2004. During
follow-up, patients with AHREs of >=5-minute duration were identified. Mortality
data were obtained from the National Death Index. RESULTS: Thirty-nine patients
(17%) had AHREs of >=5-minute duration within 6 months of pacemaker implantation.
Over a mean follow-up period of 6.6 +/- 2.0 years, the rate of all-cause
mortality was 29%. In multivariate analysis adjusted for age, sex, and
cardiovascular diseases, AHREs were associated with a significant increase in
cardiovascular mortality (hazard ratio [HR] 2.80; 95% confidence interval [CI]
1.24-6.31; P = .013) and stroke mortality (HR 9.65; 95% CI 1.56-59.9; P = .015),
with a trend toward increased all-cause mortality (HR 1.79; 95% CI 0.98-3.26; P =
.059). The subgroup of patients with AHREs of >=5-minute but <1-day duration
still had a significantly increased cardiovascular mortality (HR 3.24; 95% CI
1.37-7.66; P = .007). CONCLUSION: AHREs are commonly encountered in pacemaker
patients with no history of AF and are independent predictors of cardiovascular
mortality.
PMID- 25131668
TI - Trypsinogen activation as observed in accelerated molecular dynamics simulations.
AB - Serine proteases are involved in many fundamental physiological processes, and
control of their activity mainly results from the fact that they are synthetized
in an inactive form that becomes active upon cleavage. Three decades ago Martin
Karplus's group performed the first molecular dynamics simulations of trypsin,
the most studied member of the serine protease family, to address the transition
from the zymogen to its active form. Based on the computational power available
at the time, only high frequency fluctuations, but not the transition steps,
could be observed. By performing accelerated molecular dynamics (aMD)
simulations, an interesting approach that increases the configurational sampling
of atomistic simulations, we were able to observe the N-terminal tail insertion,
a crucial step of the transition mechanism. Our results also support the
hypothesis that the hydrophobic effect is the main force guiding the insertion
step, although substantial enthalpic contributions are important in the
activation mechanism. As the N-terminal tail insertion is a conserved step in the
activation of serine proteases, these results afford new perspective on the
underlying thermodynamics of the transition from the zymogen to the active
enzyme.
PMID- 25131669
TI - Telomerase activation after recruitment in fission yeast.
AB - Current models depict that telomerase recruitment equates to activation.
Telomeric DNA-binding proteins and the telomerase accessory proteins coordinate
the recruitment of telomerase to the ends of chromosomes in a telomere length-
and cell-cycle-dependent manner [1-4]. Recent studies have demonstrated that the
telomeric protein TPP1 and its binding protein TIN2 are key proteins for both
telomerase recruitment and processivity in mammalian cells [5-7]. Although the
precise molecular mechanism of telomerase recruitment has not yet been
established, targeted point mutations within the oligonucleotide/oligosaccharide
binding (OB)-fold domain of TPP1 have been shown to impair telomerase association
and processivity [8-10]. In fission yeast, telomerase is recruited through an
interaction between the telomerase subunit Est1 and Ccq1, a component of the Pot1
Tpz1 telomere complex (POT1-TPP1 orthologs) [11-15]. Here, we demonstrate that
association of telomerase with telomeres does not engage activity. We describe a
mutation of Tpz1 that causes critical telomere shortening despite telomeric
accumulation of the telomerase catalytic subunit, Trt1. Furthermore, Est1
directed telomerase association with Ccq1 is transient, and the Est1-Ccq1
interaction does not remain the bridge between telomeres and telomerase. Rather,
direct interaction of Trt1 with Tpz1 is critical for telomere elongation.
Moreover, Ccq1, which has been well characterized as a telomerase recruiter, is
also required for the activation of telomere-associated telomerase. Our findings
reveal a layer of telomerase regulation that controls activity after recruitment.
PMID- 25131670
TI - A bHLH complex activates vascular cell division via cytokinin action in root
apical meristem.
AB - Higher organisms possess mechanisms to maintain stem cells' proliferative and
pluripotent states in stem cell niches [1]. Plants possess two types of stem cell
niches in the root and shoot apical meristems, where regulatory interactions
exist between stem cells and organizing cells. Recent studies provided new
insights into the molecular mechanism of stem cell maintenance [2-4]. However,
earlier and more essential developmental events such as the acquisition of stem
cell proliferative activity are still unknown. In vascular tissues, procambial
cells function as stem cells and differentiate into xylem, phloem, and
procambium. Procambial cell proliferation starts at root apical meristem (RAM)
postembryonically; therefore, procambial cell development in RAM is a good model
for investigating the regulation of stem cell proliferation. LONESOME HIGHWAY
(LHW) and TARGET OF MONOPTEROS5 (TMO5), as well as its homolog, TMO5-LIKE1
(T5L1), encode bHLH proteins that function as heterodimers (LHW-TMO5 and LHW
T5L1) in vascular tissue organization [5-7]. LHW-T5L1 promotes vascular-cell
specific proliferation in RAM [7]. Here, we demonstrate that LHW-T5L1 promotes
expression of key cytokinin production genes, including LONELY GUY3 (LOG3) and
LOG4, in xylem precursor cells, resulting in elevated cytokinin levels in the
surrounding cells. LHW-T5L1 can also promote expression of AHP6, which suppresses
cytokinin signaling and then maintains xylem precursor cells at a nondividing
state. Our results indicate that LHW-T5L1 establishes xylem precursor cells as a
signal center that promotes procambial-cell-specific proliferation through
cytokinin response.
PMID- 25131672
TI - Presynaptic gain control drives sweet and bitter taste integration in Drosophila.
AB - The sense of taste is critical in determining the nutritional suitability of
foods. Sweet and bitter are primary taste modalities in mammals, and their
behavioral relevance is similar in flies. Sweet taste drives the appetitive
response to energy sources, whereas bitter taste drives avoidance of potential
toxins and also suppresses the sweet response [1, 2]. Despite their importance to
survival, little is known about the neural circuit mechanisms underlying
integration of sweet and bitter taste. Here, we describe a presynaptic gain
control mechanism in Drosophila that differentially affects sweet and bitter
taste channels and mediates integration of these opposing stimuli. Gain control
is known to play an important role in fly olfaction, where GABAB receptor
(GABABR) mediates intra- and interglomerular presynaptic inhibition of sensory
neuron output [3-5]. In the taste system, we find that gustatory receptor neurons
(GRNs) responding to sweet compounds express GABABR, whereas those that respond
to bitter do not. GABABR mediates presynaptic inhibition of calcium responses in
sweet GRNs, and both sweet and bitter stimuli evoke GABAergic neuron activity in
the vicinity of GRN axon terminals. Pharmacological blockade and genetic
reduction of GABABR both lead to increased sugar responses and decreased
suppression of the sweet response by bitter compounds. We propose a model in
which GABA acts via GABABR to expand the dynamic range of sweet GRNs through
presynaptic gain control and suppress the output of sweet GRNs in the presence of
opposing bitter stimuli.
PMID- 25131671
TI - Enhancing perception of contaminated food through acid-mediated modulation of
taste neuron responses.
AB - BACKGROUND: Natural foods contain not only nutrients, but also nonnutritious and
potentially harmful chemicals. Thus, animals need to evaluate food content in
order to make adequate feeding decisions. RESULTS: Here, we investigate the
effects of acids on the taste neuron responses and on taste behavior of
desirable, nutritious sugars and sugar/bitter compound mixtures in Drosophila
melanogaster. Using Ca2+ imaging, we show that acids activate neither sweet nor
bitter taste neurons in tarsal taste sensilla. However, they suppress responses
to bitter compounds in bitter-sensing neurons. Moreover, acids reverse
suppression of bitter compounds exerted on sweet-sensing neurons. Consistent with
these observations, behavioral analyses show that bitter-compound-mediated
inhibition on feeding behavior is alleviated by acids. To investigate the
cellular mechanism by which acids modulate these effects, we silenced bitter
sensing gustatory neurons. Surprisingly, this intervention had little effect on
acid-mediated derepression of sweet neuron or feeding responses to either
sugar/bitter compound mixtures or sugar/bitter compound/acid mixtures, suggesting
that there are two independent pathways by which bitter compounds are sensed.
CONCLUSIONS: Our investigations reveal that acids, when presented in dietary
relevant concentrations, enhance the perception of sugar/bitter compound
mixtures. Drosophila's natural food sources-fruits and cohabitating yeast-are
rich in sugars and acids but are rapidly colonized by microorganisms, such as
fungi, protozoan parasites, and bacteria, many of which produce bitter compounds.
We propose that the acids present in most fruits counteract the inhibitory
effects of these bitter compounds during feeding.
PMID- 25131673
TI - Antibiotic treatment selects for cooperative virulence of Salmonella typhimurium.
AB - Antibiotics are powerful therapeutics but are not equally effective against all
cells in bacterial populations. Bacteria that express an antibiotic-tolerant
phenotype ("persisters") can evade treatment [1]. Persisters can cause relapses
of the infection after the end of the therapy [2]. It is still poorly understood
whether persistence affects the evolution of bacterial virulence. During
infections, persisters have been found preferentially at particular sites within
the host [3, 4]. If bacterial virulence factors are required to reach such sites,
treatment with antibiotics could impose selection on the expression of virulence
genes, in addition to their well-established effects on bacterial resistance.
Here, we report that treatment with antibiotics selects for virulence and fosters
transmissibility of Salmonella Typhimurium. In a mouse model for Salmonella
diarrhea, treatment with the broad-spectrum antibiotic ciprofloxacin reverses the
outcome of competition between wild-type bacteria and avirulent mutants that can
spontaneously arise during within-host evolution [5]. While avirulent mutants
take over the gut lumen and abolish disease transmission in untreated mice,
ciprofloxacin tilts the balance in favor of virulent, wild-type bacteria. This is
explained by the need for virulence factors to invade gut tissues and form a
persistent reservoir. Avirulent mutants remain in the gut lumen and are
eradicated. Upon cessation of antibiotic treatment, tissue-lodged wild-type
pathogens reseed the gut lumen and thereby facilitate disease transmissibility to
new hosts. Our results suggest a general principle by which antibiotic treatment
can promote cooperative virulence during within-host evolution, increase duration
of transmissibility, and thereby enhance the spread of an infectious disease.
PMID- 25131674
TI - Endogenous species of mammalian nonmuscle myosin IIA and IIB include activated
monomers and heteropolymers.
AB - BACKGROUND: Class II myosins generate contractile forces in cells by polymerizing
into bipolar filaments and pulling on anchored actin filaments. Nonmuscle myosin
II (NMII) plays central roles during cell adhesion, migration, cytokinesis, and
tissue morphogenesis. NMII is present in virtually all mammalian cell types as
tissue-specific combinations of NMIIA, NMIIB, and NMIIC isoforms. It remains
poorly understood how the highly dynamic NMII-actin contractile system begins to
assemble at new cellular locations during cell migration and how incorporation of
different NMII isoforms into this system is coordinated. RESULTS: Using platinum
replica electron microscopy in combination with immunogold labeling, we
demonstrate that individual activated (phosphorylated on the regulatory light
chain and unfolded) NMIIA and NMIIB molecules represent a functional form of NMII
in motile cells and that NMIIA and NMIIB copolymerize into nascent bipolar
filaments during contractile system assembly. Using subdiffraction stimulated
emission depletion microscopy together with a pharmacological block-and-release
approach, we report that NMIIA and NMIIB simultaneously incorporate into the
cytoskeleton during initiation of contractile system assembly, whereas the
characteristic rearward shift of NMIIB relative to NMIIA is established later in
the course of NMII turnover. CONCLUSIONS: We show existence of activated NMII
monomers in cells, copolymerization of endogenous NMIIA and NMIIB molecules, and
contribution of both isoforms, rather than only NMIIA, to early stages of the
contractile system assembly. These data change the current paradigms about
dynamics and functions of NMII and provide new conceptual insights into the
organization and dynamics of the ubiquitous cellular machinery for contraction
that acts in multiple cellular contexts.
PMID- 25131676
TI - Individual behaviors dominate the dynamics of an urban mountain lion population
isolated by roads.
AB - Large carnivores can be particularly sensitive to the effects of habitat
fragmentation on genetic diversity [1, 2]. The Santa Monica Mountains (SMMs), a
large natural area within Greater Los Angeles, is completely isolated by urban
development and the 101 freeway to the north. Yet the SMMs support a population
of mountain lions (Puma concolor), a very rare example of a large carnivore
persisting within the boundaries of a megacity. GPS locations of radio-collared
lions indicate that freeways are a near-absolute barrier to movement. We
genotyped 42 lions using 54 microsatellite loci and found that genetic diversity
in SMM lions, prior to 2009, was lower than that for any population in North
America except in southern Florida, where inbreeding depression led to
reproductive failure [3-5]. We document multiple instances of father-daughter
inbreeding and high levels of intraspecific strife, including the unexpected
behavior of a male killing two of his offspring and a mate and his son killing
two of his brothers. Overall, no individuals from the SMMs have successfully
dispersed. Gene flow is critical for this population, and we show that a single
male immigrated in 2009, successfully mated, and substantially enhanced genetic
diversity. Our results imply that individual behaviors, most likely caused by
limited area and reduced opportunities to disperse, may dominate the fate of
small, isolated populations of large carnivores. Consequently, comprehensive
behavioral monitoring can suggest novel solutions for the persistence of small
populations, such as the transfer of individuals across dispersal barriers.
PMID- 25131675
TI - Self-generated movements with "unexpected" sensory consequences.
AB - The nervous systems of diverse species, including worms and humans, possess
mechanisms for distinguishing between sensations arising from self-generated
(i.e., expected) movements from those arising from other-generated (i.e.,
unexpected) movements [1-3]. To make this critical distinction, animals generate
copies, or corollary discharges, of motor commands [4, 5]. Corollary discharge
facilitates the selective gating of reafferent signals arising from self
generated movements, thereby enhancing detection of novel stimuli [6-10].
However, for a developing nervous system, such sensory gating would be
counterproductive if it impedes transmission of the very activity upon which
activity-dependent mechanisms depend [11]. In infant rats during active (or REM)
sleep--a behavioral state that predominates in early infancy [12-16]--neural
circuits within the brainstem [17, 18] trigger hundreds of thousands of myoclonic
twitches each day [19]. The putative contribution of these self-generated
movements to the activity-dependent development of the sensorimotor system is
supported by the observation that reafference from twitching limbs reliably and
substantially triggers brain activity [20-23]. In contrast, under identical
testing conditions, even the most vigorous wake movements reliably fail to
trigger reafferent brain activity [21-23]. One hypothesis that accounts for this
paradox is that twitches, uniquely among self-generated movements, lack corollary
discharge [23]. Here, we test this hypothesis in newborn rats by manipulating the
degree to which self-generated movements are expected and, therefore, their
presumed recruitment of corollary discharge. We show that twitches, although self
generated, are processed as if they are unexpected.
PMID- 25131677
TI - Gating characteristics control glutamate receptor distribution and trafficking in
vivo.
AB - Glutamate-releasing synapses dominate excitatory release in the brain. Mechanisms
governing their assembly are of major importance for circuit development and long
term plasticity underlying learning and memory. AMPA/Kainate-type glutamate
receptors (GluRs) are tetrameric ligand-gated ion channels that open their ion
conducting pores in response to binding of the neurotransmitter. Changes in
subunit composition of postsynaptic GluRs are highly relevant for plasticity and
development of glutamatergic synapses [1-4]. To date, posttranslational
modifications, mostly operating via the intracellular C-terminal domains (CTDs)
of GluRs, are presumed to be the major regulator of trafficking [5]. In recent
years, structural and electrophysiological analyses have improved our
understanding of GluR gating mechanism [6-11]. However, whether conformational
changes subsequent to glutamate binding may per se be able to influence GluR
trafficking has remained an unaddressed question. Using a Drosophila system
allowing for extended visualization of GluR trafficking in vivo, we here provide
evidence that mutations changing the gating behavior alter GluR distribution and
trafficking. GluR mutants associated with reduced charge transfer segregated from
coexpressed wild-type GluRs on the level of individual postsynaptic densities.
Segregation was lost upon blocking of evoked glutamate release. Photobleaching
experiments suggested increased mobility of mutants with reduced charge transfer,
which accumulated prematurely during early steps of synapse assembly, but failed
to further increase their level in accordance with assembly of the presynaptic
scaffold. In summary, gating characteristics seem to be a new variable for the
understanding of GluR trafficking relevant to both development and plasticity.
PMID- 25131678
TI - Combined TMS and FMRI reveal dissociable cortical pathways for dynamic and static
face perception.
AB - Faces contain structural information, for identifying individuals, as well as
changeable information, which can convey emotion and direct attention.
Neuroimaging studies reveal brain regions that exhibit preferential responses to
invariant [1, 2] or changeable [3-5] facial aspects but the functional
connections between these regions are unknown. We addressed this issue by
causally disrupting two face-selective regions with thetaburst transcranial
magnetic stimulation (TBS) and measuring the effects of this disruption in local
and remote face-selective regions with functional magnetic resonance imaging
(fMRI). Participants were scanned, over two sessions, while viewing dynamic or
static faces and objects. During these sessions, TBS was delivered over the right
occipital face area (rOFA) or right posterior superior temporal sulcus (rpSTS).
Disruption of the rOFA reduced the neural response to both static and dynamic
faces in the downstream face-selective region in the fusiform gyrus. In contrast,
the response to dynamic and static faces was doubly dissociated in the rpSTS.
Namely, disruption of the rOFA reduced the response to static but not dynamic
faces, while disruption of the rpSTS itself reduced the response to dynamic but
not static faces. These results suggest that dynamic and static facial aspects
are processed via dissociable cortical pathways that begin in early visual
cortex, a conclusion inconsistent with current models of face perception [6-9].
PMID- 25131680
TI - (NH4)2SO4 recovery from liquid side streams.
AB - Two methods of recovering nitrogen from liquid side streams are presented in this
paper. The first method was demonstrated at an ammonia stripping plant treating 5
7 m(3)/h sludge water at the wastewater treatment plant (WWTP) Kloten-Opfikon
(CH). In addition to the usual stripping and scrubbing columns, a third column
had been added in order strip CO2, thus reducing the NaOH-demand of the
subsequent ammonia stripping. At first, just the stripping plant was put into
operation and optimized without any pre-treatment of the supernatant. Next, the
CO2-stripper column was activated and optimized by gas measurements to minimize
free ammonia losses, heat losses, and energy consumption. Key operational aspects
of the plant were evaluated. Finally, up to 1.4 m(3)/h source-separated urine was
successfully fed into the stripping facility. The second ammonia removal method
using hydrophobic hollow fiber membranes was tested in two small pilot systems by
different manufacturers in 2012 and 2013 at WWTP Neugut. In this technology, free
ammonia gas in the sludge liquid diffuses at pH >9.3 from the sludge liquid
through the air-filled pores of the microporous hydrophobic membrane into
concentrated sulfuric acid flowing through the hollow fibers, forming ammonium
sulfate. The small pore size and the hydrophobic nature of the membrane prevent
the liquid phase from entering into the pores due to the surface tension effect.
Practical experience regarding operational parameters like wastewater flow rate,
pH, temperature, ammonia concentration, fouling and precipitations processes,
optimal flow schemes, and process configurations was collected.
PMID- 25131679
TI - Does a short-term exposure to cadmium chloride affects haemocyte parameters of
the marine gastropod Haliotis tuberculata?
AB - In this study, a model based on primary cultured haemocytes from the gastropod
mollusc Haliotis tuberculata was established to investigate the effects of
cadmium chloride in vitro. Cells were exposed for 24 h to CdCl2 concentrations of
0, 1 and 100 MUg ml(-1). The effects of cadmium on haemocyte parameters were
investigated using morphological, spectrophotometric and flow cytometry analysis.
Results showed that cadmium has no significant effects on cell viability and
phagocytotic activity under the tested conditions. However, haemocytes became
more rounded after cadmium exposure, which could explain the significant decrease
of cell area beginning at 1 MUg ml(-1) of CdCl2.
PMID- 25131681
TI - Molecular markers in ambient aerosol in the Mahanadi Riverside Basin of eastern
central India during winter.
AB - Organic molecular markers are important atmospheric constituents. Their formation
and sources are important aspects of the study of urban and rural air quality. We
collected PM10 aerosol samples from the Mahanadi Riverside Basin (MRB), a rural
part of eastern central India, during the winter of 2011. PM10 aerosols were
characterized for molecular markers using ion chromatography. The concentration
of PM10 ranged from 208.8 to 588.3 MUg m(-3) with a mean concentration of 388.9
MUg m(-3). Total concentration of anhydrosugars, sugar alcohols, primary sugars,
and oxalate were found to be 3.25, 5.60, 10.52, and 0.37 MUg m(-3), respectively,
during the study period. Glucose was the most abundant species followed by
levoglucosan and mannitol. Significant positive correlation between the molecular
markers, anhydrosugars, sugar alcohols, primary sugars, and oxalic acid confirmed
that biomass burning, biogenic activity, and re-suspension of soil particles were
the main sources of aerosol in the eastern central India study area.
PMID- 25131682
TI - Multiple linear regression model for bromate formation based on the survey data
of source waters from geographically different regions across China.
AB - A total of 86 source water samples from 38 cities across major watersheds of
China were collected for a bromide (Br(-)) survey, and the bromate (BrO3 (-))
formation potentials (BFPs) of 41 samples with Br(-) concentration >20 MUg L(-1)
were evaluated using a batch ozonation reactor. Statistical analyses indicated
that higher alkalinity, hardness, and pH of water samples could lead to higher
BFPs, with alkalinity as the most important factor. Based on the survey data, a
multiple linear regression (MLR) model including three parameters (alkalinity,
ozone dose, and total organic carbon (TOC)) was established with a relatively
good prediction performance (model selection criterion = 2.01, R (2) = 0.724),
using logarithmic transformation of the variables. Furthermore, a contour plot
was used to interpret the influence of alkalinity and TOC on BrO3 (-) formation
with prediction accuracy as high as 71 %, suggesting that these two parameters,
apart from ozone dosage, were the most important ones affecting the BFPs of
source waters with Br(-) concentration >20 MUg L(-1). The model could be a useful
tool for the prediction of the BFPs of source water.
PMID- 25131683
TI - Ecocatalysis for 2H-chromenes synthesis: an integrated approach for
phytomanagement of polluted ecosystems.
AB - A direct, general and efficient method to synthesize 2H-chromenes (2H
benzo[b]pyrans), identified as environmentally friendly pesticides, has been
developed. This approach lays on the new concept of ecocatalysis, which involves
the use of biomass from phytoextraction processes, as a valuable source of
metallic elements for chemical synthesis. This methodology is similar or superior
to known methods, affording 2H-chromenes with good to excellent yields (60-98%),
including the preparation of precocene I, a natural insect growth regulator, with
91% yield. The approach is ideal for poor reactive substrates such as phenol or
naphthol, classically transformed into 2H-chromenes by methodologies associated
with environmental issues. These results illustrate the interest of combining
phytoextraction and green synthesis of natural insecticides.
PMID- 25131684
TI - Quasi-simultaneous in-line flue gas monitoring of NO and NO2 emissions at a
caloric power plant employing mid-IR laser spectroscopy.
AB - Two pulsed thermoelectrically cooled mid-infrared distributed feedback quantum
cascade lasers (QCLs) were used for the quasi-simultaneous in-line determination
of NO and NO2 at the caloric power plant Durnrohr (Austria). The QCL beams were
combined using a bifurcated hollow fiber, sent through the flue tube (inside
diameter: 5.5 m), reflected by a retro-reflector and recorded using a fast
thermoelectrically cooled mercury-cadmium-telluride detector. The thermal chirp
during 300 ns pulses was about 1.2 cm(-1) and allowed scanning of rotational
vibrational doublets of the analytes. On the basis of the thermal chirp and the
temporal resolution of data acquisition, a spectral resolution of approximately
0.02 cm(-1) was achieved. The recorded rotational vibrational absorption lines
were centered at 1900 cm(-1) for NO and 1630 cm(-1) for NO2. Despite water
content in the range of 152-235 g/m(3) and an average particle load of 15.8
mg/m(3) in the flue gas, in-line measurements were possible achieving limits of
detection of 73 ppb for NO and 91 ppb for NO2 while optimizing for a single
analyte. Quasi-simultaneous measurements resulted in limits of detection of 219
ppb for NO and 164 ppb for NO2, respectively. Influences of temperature and
pressure on the data evaluation are discussed, and results are compared to an
established reference method based on the extractive measurements presented.
PMID- 25131686
TI - A tribute to Dr. Steve Haskins.
PMID- 25131685
TI - Relative value of ultrasound, computed tomography and positron emission
tomography imaging in the clinically node-negative neck in oral cancer.
AB - AIM: To determine the most accurate noninvasive imaging modality for occult
metastasis in clinically node-negative necks in oral squamous cell carcinoma from
a granulomatous disease endemic region. METHOD: Prospective, observational study
comparing ultrasound (US), contrast enhanced computed tomography (CECT) and
positron emission tomography-computed tomography (PET-CT). Level wise assessment
of neck nodes with each imaging modality was performed and compared with final
histopathology. RESULTS: Eighty-five necks were evaluated in 70 patients.
Sensitivity, specificity and accuracy of the three modalities were 78.9, 68.75
and 73.25% for US, 73.6, 85.4 and 80.2% for CECT, and 81.5, 54.1 and 66.2% for
PET-CT, respectively. CECT performed better than US and PET-CT scan particularly
in levels IB and II (accuracy of 81.4 and 88.3% for CECT, 73.25 and 79.1% for US,
and 68.6 and 68.6% for PET-CT scan, respectively). Concordance with histology was
best with CECT (kappa = 0.615) followed by US (kappa = 0.461) and PET-CT (kappa =
0.337). CONCLUSION: The quest for the most accurate imaging modality in
clinically node-negative necks continues. US alone is inadequate. While PET-CT
may not be a specific imaging modality in detecting occult cervical nodal
metastasis in endemic regions of chronic granulomatous diseases, the performance
of PET CECT in this setting remains to be evaluated. CECT scan, routinely used in
imaging for primary disease, is fairly accurate in detecting nodal metastasis.
However, in early oral cancers that are generally treated without any imaging for
the primary tumor, management of the neck will largely depend on clinical
judgment.
PMID- 25131687
TI - Prevalence of celiac disease autoimmunity in children with type 1 diabetes:
regional variations across the Oresund strait between Denmark and southernmost
Sweden.
AB - OBJECTIVES: The aim was to determine the prevalence of celiac disease
autoimmunity in children with type 1 diabetes (T1D) diagnosed in Denmark and
Sweden. METHODS: A total of 662 Swedish children with T1D were matched with 1080
Danish children with T1D and 309 healthy children from Sweden and 283 from
Denmark served as controls. Sera were analyzed for the presence of IgA and IgG
(IgAG) autoantibodies against deamidated gliadin peptide (DGP) and tissue
transglutaminase (tTG) with enzyme-linked immunosorbent assay (ELISA) and IgG-tTG
separately in a radioligand binding assay (RBA). Human leukocyte antigen (HLA)
DQB1 and DQA1 genotyping were determined in the T1D cohorts. RESULTS: In the
Swedish T1D cohort, 17.2% (114/662) were IgAG-DGP/tTG positive compared with
11.7% (126/1080) in the Danish T1D cohort (p = 0.001) and with 9.4% (29/309)
Swedish (p = 0.001) and 5.7% (16/283) Danish (p = 0.003) controls. In the Swedish
T1D cohort, both levels of IgAG-DGP/tTG and IgG-tTG were higher compared with the
levels in the Danish T1D (p < 0.001). In the control group, 2.8% of the Danish
children were positive for both IgAG-DGP/tTG and IgG-tTG, compared to 0.3% of the
Swedish. Presence of HLA-DQ2 was equally distributed among 89 children with T1D
positive for both IgAG-DGP/tTG and IgG-tTG. CONCLUSION: The discrepancy in levels
of IgAG-DGP/tTG and IgG-tTG between Swedish and Danish T1D cohorts was
independent of HLA and suggests that regional variations in comorbidity of celiac
disease in T1D is caused by difference in exposure to environmental factors.
PMID- 25131688
TI - Improving sensitivity for serodiagnosis of tuberculosis using TB16.3-echA1 fusion
protein.
AB - This study aimed at developing and assessing the fusion proteins with enhanced
sensitivity to detect antibodies in plasma as a diagnostic method for
tuberculosis. DNA fragments encoding TB16.3 and echA1 gene regions corresponding
to proteins TB16.3 and echA1 from Mycobacterium tuberculosis were amplified
through PCR. Through a series of restrictions and ligations two novel fusion
constructs TB16.3-echA1 and TB16.3-tnPstS1 were produced and expressed in
Escherichia coli. These were screened for detection of antibodies in human
plasma. The individual antigens TB16.3, echA1 and tnPstS1 and the fusion protein
TB16.3-tnPstS1 and TB16.3-echA1 showed sensitivities of 29%, 25.5%, 42.8%, 40.0%
and 47.2%, respectively. Lower sensitivity in case of TB16.3-tnPstS1 seems to be
due to the structural arrangement between the two proteins, which is likely to
mask several of their epitopes. The higher sensitivity of TB16.3-echA1 appears to
be due to lesser interaction between the two proteins thus allowing free
availability of epitopes for binding antibodies. 64% of TB patients were found
positive for either one of the two fusion proteins TB16.3-echA1 and TB16.3
tnPstS1. This study indicates that the novel fusion protein TB16.3-echA1 has a
potential in serodiagnosis of TB with improved sensitivity and reliability.
PMID- 25131689
TI - Tanycytes: a gateway to the metabolic hypothalamus.
AB - The central regulation of energy balance relies on the ability of the brain to
promptly and efficiently sense variations of metabolic state. To achieve this,
circulating hormonal and metabolic signals have to cross the blood-brain
interface, where unusual glial cells named tanycytes have been described to play
a key role in this process. Tanycytes are specialised polarised ependymoglial
cells that line the floor of the third ventricle and send a single process to
contact hypothalamic neurones and blood vessels. Although their role in the
regulation of energy balance via the modulation of neuronal activity or their
chemosensitivity has been already described, recent studies ascribe a new
function to tanycytes in the regulation of energy homeostasis as a result of
their capacity to regulate the access of metabolic signals to the hypothalamus.
This review discusses the peculiar place of tanycytes within the blood
hypothalamus interface, as well as a striking capacity to remodel their own
interface to ensure an adaptive metabolic response to energy imbalances.
PMID- 25131690
TI - Resting-state functional connectivity of the human hypothalamus.
AB - The hypothalamus is of enormous importance for multiple bodily functions such as
energy homeostasis. Especially, rodent studies have greatly contributed to our
understanding how specific hypothalamic subregions integrate peripheral and
central signals into the brain to control food intake. In humans, however, the
neural circuitry of the hypothalamus, with its different subregions, has not been
delineated. Hence, the aim of this study was to map the hypothalamus network
using resting-state functional connectivity (FC) analyses from the medial
hypothalamus (MH) and lateral hypothalamus (LH) in healthy normal-weight adults
(n = 49). Furthermore, in a separate sample, we examined differences within the
LH and MH networks between healthy normal-weight (n = 25) versus overweight/obese
adults (n = 23). FC patterns from the LH and MH revealed significant connections
to the striatum, thalamus, brainstem, orbitofrontal cortex, middle and posterior
cingulum and temporal brain regions. However, our analysis revealed subtler
distinctions within hypothalamic subregions. The LH was functionally stronger
connected to the dorsal striatum, anterior cingulum, and frontal operculum, while
the MH showed stronger functional connections to the nucleus accumbens and medial
orbitofrontal cortex. Furthermore, overweight/obese participants revealed
heightened FC in the orbitofrontal cortex and nucleus accumbens within the MH
network. Our results indicate that the MH and LH network are tapped into
different parts of the dopaminergic circuitry of the brain, potentially
modulating food reward based on the functional connections to the ventral and
dorsal striatum, respectively. In obese adults, FC changes were observed in the
MH network.
PMID- 25131693
TI - Inhibition of angiotensin-converting enzyme increases oestradiol production in
ewes submitted to oestrous synchronization protocol.
AB - This study aimed at evaluating the effects of angiotensin-converting enzyme
inhibitor (enalapril) and angiotensin II antagonist (valsartan) on the oestradiol
and progesterone production in ewes submitted to oestrous synchronization
protocol. The animals were weighed and randomly divided into three groups (n =
7). A pre-experiment conducted to verify the effectiveness and toxicity of
enalapril (0.5 mg/kg LW) and valsartan (2.2 mg/kg LW) showed that, in the doses
used, these drugs were effective in reducing blood pressure without producing
toxic effects. In the experiment, all animals were subjected to oestrous
synchronization protocol during 12 days. On D10, D11 and D12, animals received
saline, enalapril or valsartan (same doses of the pre-experiment), according to
the group randomly divided. The hormonal analysis showed an increase in
oestradiol on the last day of the protocol (D12) in animals that received
enalapril (p < 0.05), but not in other groups, without changing the concentration
of progesterone in any of the treatments. It is concluded that valsartan and
enalapril are safe and effective subcutaneously for use in sheep and that the
angiotensin-converting enzyme (ACE) inhibition with enalapril leads to an
increase in oestradiol production near ovulation without changing the
concentration of progesterone. This shows that ACE inhibition may be a useful
tool in reproductive biotechnologies involving induction and synchronization of
oestrus and ovulation in sheep.
PMID- 25131694
TI - The iPod binocular home-based treatment for amblyopia in adults: efficacy and
compliance.
AB - BACKGROUND: Occlusion therapy for amblyopia is predicated on the idea that
amblyopia is primarily a disorder of monocular vision; however, there is growing
evidence that patients with amblyopia have a structurally intact binocular visual
system that is rendered functionally monocular due to suppression. Furthermore,
we have found that a dichoptic treatment intervention designed to directly target
suppression can result in clinically significant improvement in both binocular
and monocular visual function in adult patients with amblyopia. The fact that
monocular improvement occurs in the absence of any fellow eye occlusion suggests
that amblyopia is, in part, due to chronic suppression. Previously the treatment
has been administered as a psychophysical task and more recently as a video game
that can be played on video goggles or an iPod device equipped with a lenticular
screen. The aim of this case-series study of 14 amblyopes (six strabismics, six
anisometropes and two mixed) ages 13 to 50 years was to investigate: 1. whether
the portable video game treatment is suitable for at-home use and 2. whether an
anaglyphic version of the iPod-based video game, which is more convenient for at
home use, has comparable effects to the lenticular version. METHODS: The
dichoptic video game treatment was conducted at home and visual functions
assessed before and after treatment. RESULTS: We found that at-home use for 10 to
30 hours restored simultaneous binocular perception in 13 of 14 cases along with
significant improvements in acuity (0.11 +/- 0.08 logMAR) and stereopsis (0.6 +/-
0.5 log units). Furthermore, the anaglyph and lenticular platforms were equally
effective. In addition, the iPod devices were able to record a complete and
accurate picture of treatment compliance. CONCLUSION: The home-based dichoptic
iPod approach represents a viable treatment for adults with amblyopia.
PMID- 25131695
TI - Contemporary evidence-based guidelines: practice based on the strongest evidence.
PMID- 25131692
TI - Mutant disrupted-in-schizophrenia 1 in astrocytes: focus on glutamate metabolism.
AB - Disrupted-in-schizophrenia 1 (DISC1) is a genetic risk factor that has been
implicated in major mental disorders. DISC1 binds to and stabilizes serine
racemase to regulate production of D-serine by astrocytes, contributing to
glutamate (GLU) neurotransmission. However, the possible involvement of
astrocytic DISC1 in synthesis, metabolism, reuptake, or secretion of GLU remains
unexplored. Therefore, we studied the effects of dominant-negative mutant DISC1
on various aspects of GLU metabolism by using primary astrocyte cultures and
hippocampal tissue from transgenic mice with astrocyte-restricted expression of
mutant DISC1. Although mutant DISC1 had no significant effects on astrocyte
proliferation, GLU reuptake, glutaminase, or glutamate carboxypeptidase II
activity, expression of mutant DISC1 was associated with increased levels of
alanine-serine-cysteine transporter 2, vesicular glutamate transporters 1 and 3
in primary astrocytes and in the hippocampus, and elevated expression of the NR1
subunit and diminished expression of the NR2A subunit of N-methyl-D-aspartate
(NMDA) receptors in the hippocampus, at postnatal day 21. Our findings indicate
that decreased D-serine production by astrocytic mutant DISC1 might lead to
compensatory changes in levels of the amino acid transporters and NMDA receptors
in the context of tripartite synapse.
PMID- 25131696
TI - A perspective on the New American College of Cardiology/American Heart
Association guidelines for cardiovascular risk assessment.
AB - The recently published American College of Cardiology (ACC)/American Heart
Association (AHA) guidelines for cardiovascular risk assessment provide equations
to estimate the 10-year and lifetime atherosclerotic cardiovascular disease
(ASCVD) risk in African Americans and non-Hispanic whites, include stroke as an
adverse cardiovascular outcome, and emphasize shared decision making. The
guidelines provide a valuable framework that can be adapted on the basis of
clinical judgment and individual/institutional expertise. In this review, we
provide a perspective on the new guidelines, highlighting what is new, what is
controversial, and potential adaptations. We recommend obtaining family history
of ASCVD at the time of estimating ASCVD risk and consideration of imaging to
assess subclinical disease burden in patients at intermediate risk. In addition
to the adjuncts for ASCVD risk estimation recommended in the guidelines, measures
that may be useful in refining risk estimates include carotid ultrasonography,
aortic pulse wave velocity, and serum lipoprotein(a) levels. Finally, we stress
the need for research efforts to improve assessment of ASCVD risk given the
suboptimal performance of available risk algorithms and suggest potential future
directions in this regard.
PMID- 25131691
TI - Mechanisms of abnormal lamellar body secretion and the dysfunctional skin barrier
in patients with atopic dermatitis.
AB - I review how diverse inherited and acquired abnormalities in epidermal structural
and enzymatic proteins converge to produce defective permeability barrier
function and antimicrobial defense in patients with atopic dermatitis (AD).
Although best known are mutations in filaggrin (FLG), mutations in other member
of the fused S-100 family of proteins (ie, hornerin [hrn] and filaggrin 2 [flg
2]); the cornified envelope precursor (ie, SPRR3); mattrin, which is encoded by
TMEM79 and regulates the assembly of lamellar bodies; SPINK5, which encodes the
serine protease inhibitor lymphoepithelial Kazal-type trypsin inhibitor type 1;
and the fatty acid transporter fatty acid transport protein 4 have all been
linked to AD. Yet these abnormalities often only predispose to AD; additional
acquired stressors that further compromise barrier function, such as
psychological stress, low ambient humidity, or high-pH surfactants, often are
required to trigger disease. T(H)2 cytokines can also compromise barrier function
by downregulating expression of multiple epidermal structural proteins, lipid
synthetic enzymes, and antimicrobial peptides. All of these inherited and
acquired abnormalities converge on the lamellar body secretory system, producing
abnormalities in lipid composition, secretion, and/or extracellular lamellar
membrane organization, as well as antimicrobial defense. Finally, I briefly
review therapeutic options that address this new pathogenic paradigm.
PMID- 25131697
TI - A summary and critical assessment of the 2013 ACC/AHA guideline on the treatment
of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in
adults: filling the gaps.
AB - The American College of Cardiology/American Heart Association (ACC/AHA) Task
Force on Practice Guidelines has recently released the new cholesterol treatment
guideline. This update was based on a systematic review of the evidence and
replaces the previous guidelines from 2002 that were widely accepted and
implemented in clinical practice. The new cholesterol treatment guideline
emphasizes matching the intensity of statin treatment to the level of
atherosclerotic cardiovascular disease (ASCVD) risk and replaces the old paradigm
of pursuing low-density lipoprotein cholesterol targets. The new guideline also
emphasizes the primacy of the evidence base for statin therapy for ASCVD risk
reduction and lists several patient groups that will not benefit from statin
treatment despite their high cardiovascular risk, such as those with heart
failure (New York Heart Association class II-IV) and patients undergoing
hemodialysis. The guideline has been received with mixed reviews and significant
controversy. Because of the evidence-based nature of the guideline, there is room
for several questions and uncertainties on when and how to use lipid-lowering
therapy in clinical practice. The goal of the Mayo Clinic Task Force in the
assessment, interpretation, and expansion of the ACC/AHA cholesterol treatment
guideline is to address gaps in information and some of the controversial aspects
of the newly released cholesterol management guideline using additional sources
of evidence and expert opinion as needed to guide clinicians on key aspects of
ASCVD risk reduction.
PMID- 25131698
TI - Pattern and factors associated with utilization of dental services among older
adults in rural Victoria.
AB - BACKGROUND: In Australia, rural and regional areas have an increased proportion
of older people who are ageing more rapidly than their metropolitan counterparts.
This increase in the ageing population and its uneven geographic distribution is
likely to pose an oral health challenge in the near future. METHODS: A cross
sectional study conducted in a sample of 226 community-dwelling adults aged 55
years and older, living in the City of Greater Bendigo who completed a
questionnaire and received an oral examination. RESULTS: Overall, 51.2% of
participants reported having been to the dentist in the previous 12 months.
Reported barriers to dental care were: cost of services (32.7%), fear of dentists
(25.8%), length of waiting lists (18.1%) and availability of oral health care
services (11.1%). Living alone, gender, low income, lack of education, low self
perceived oral health needs, self-perceived barriers, edentulism, and presence of
mobility problems were statistically significant variables associated with less
use of dental services (p < 0.0001). CONCLUSIONS: Access to dental care is
affected by financial and structural barriers as well as other predisposing and
enabling factors among older adults. Thus, increase in user services will require
efforts to reduce financial barriers and make dental care culturally and
linguistically competent.
PMID- 25131699
TI - Minimally invasive neurosurgical access techniques to facilitate endovascular
treatment of dural arteriovenous fistulae.
AB - We report two cases of dural arteriovenous fistulae treated endovascularly, where
percutaneous venous or arterial access was not suitable. In both cases, a
different surgical access technique was used to allow transcranial cannulation of
the appropriate venous sinus or of the varix to gain access and occlude the
fistula.
PMID- 25131700
TI - Visualizing an ultra-weak protein-protein interaction in phosphorylation
signaling.
AB - Proteins interact with each other to fulfill their functions. The importance of
weak protein-protein interactions has been increasingly recognized. However,
owing to technical difficulties, ultra-weak interactions remain to be
characterized. Phosphorylation can take place via a K(D)~25 mM interaction
between two bacterial enzymes. Using paramagnetic NMR spectroscopy and with the
introduction of a novel Gd(III)-based probe, we determined the structure of the
resulting complex to atomic resolution. The structure accounts for the mechanism
of phosphoryl transfer between the two enzymes and demonstrates the physical
basis for their ultra-weak interaction. Further, molecular dynamics (MD)
simulations suggest that the complex has a lifetime in the micro- to millisecond
regimen. Hence such interaction is termed a fleeting interaction. From
mathematical modeling, we propose that an ultra-weak fleeting interaction enables
rapid flux of phosphoryl signal, providing a high effective protein
concentration.
PMID- 25131702
TI - Young chemists and the European Young Chemist Award.
PMID- 25131701
TI - Gamma Glutamyl Transferase Activity is Associated With Both Paraoxonase Activity
and Aortic Stiffness in Hypertensive Patients.
AB - BACKGROUND: We aimed to investigate relationship between gamma glutamyl
transferase (GGT) activity with paraoxonase 1 (PON1) activity and aortic
stiffness (AS) parameters such as pulse wave velocity (PWV) and augmentation
index (AIx). METHODS: Measurements were obtained from 324 patients with newly
diagnosed essential hypertension (mean age: 55.0 +/- 8.2 years). The patients
were divided into two groups according to their median GGT values. PWV and AIx
were calculated using the single-point method via the Mobil-O-Graph(r) ARCsolver
algorithm. RESULTS: PWV, Aix, and high-sensitive C-reactive protein (hs-CRP)
values were higher and PON1 activity values were lower in GGThigh group compared
with GGTlow group (P < 0.05, for all). Multiple linear regression analysis showed
that GGT activity was independently associated with PWV (beta = 0.496, P < 0.001)
and PON1 activity (beta = -0.343, P < 0.001) as well as hs-CRP (beta = 0.334, P <
0.001). CONCLUSION: These results may support that increased GGT activity would
be associated with both impaired antioxidant system and increased AS in
hypertensive patients.
PMID- 25131705
TI - Identification of the novel KIR2DL3*030 allele from a southern Chinese Han
individual.
AB - KIR2DL3*030 differs from the closest allele, KIR2DL3*00101, by a single missense
mutation at CDS.
PMID- 25131706
TI - Brain penetration of emodepside is increased in P-glycoprotein-deficient mice and
leads to neurotoxicosis.
AB - The antiparasitic drug emodepside (EMO) is a substrate of the P-glycoprotein
multidrug efflux carrier (P-gp; syn. MDR1, ABCB1), which has an important
function in protecting the brain from potentially toxic compounds by functional
drug efflux at the blood-brain barrier (BBB). Many dogs of the Collie breed and
even dogs of many other breeds have a loss-of-function 4-bp deletion mutation in
the MDR1 gene. In these dogs, brain penetration of many P-gp-transported drugs is
increased and so their therapeutic usage is restricted. To elucidate the role of
P-gp at the BBB for the brain penetration of EMO, we applied EMO at 1 mg/kg to
mdr1-deficient (PGP(mut) ) and mdr1-intact (PGP(WT) ) CF1 mice. Whereas in the
brain of the PGP(WT) mice, EMO was below the detection level of 10 ng/g, its
concentration was at 43.7 ng/g in the PGP(mut) mice. Furthermore, appearance of
neurological toxicity was analyzed in these mice after application of 1 mg/kg EMO
using a rotarod setup. In all PGP(mut) mice, but not in the PGP(WT) mice, the
walking performance on the rotarod was impaired by EMO with clear differences in
the degree and duration of neurological toxicity. Some of the mice were
completely unable to walk on the rotarod already at 2 h after drug application
and showed long-lasting ataxia over >24 h. Others even showed significantly
reduced walking performance, but completely recovered within 1 day. In
conclusion, P-gp restricts brain penetration of EMO and prevents neurological
toxicity of this drug in mice.
PMID- 25131707
TI - Meta-analysis and meta-regression analysis of biomarkers for abdominal aortic
aneurysm.
AB - BACKGROUND: Many studies have investigated the systemic and local expression of
biomarkers in patients with abdominal aortic aneurysm (AAA). The natural history
of AAA varies between patients, and predictors of the presence and diameter of
AAA have not been determined consistently. The aim of this study was to perform a
systematic review, meta-analysis and meta-regression of studies comparing
biomarkers in patients with and without AAA, with the aim of summarizing the
association of identified markers with both AAA presence and size. METHODS AND
RESULTS: Literature review identified 106 studies suitable for inclusion. Meta
analysis demonstrated a significant difference between matrix metalloproteinase
(MMP) 9, tissue inhibitor of matrix metalloproteinase 1, interleukin (IL) 6, C
reactive protein (CRP), alpha1-antitrypsin, triglycerides, lipoprotein(a),
apolipoprotein A and high-density lipoprotein in patients with and without AAA.
Although meta-analysis was not possible for MMP-2 in aortic tissue, tumour
necrosis factor alpha, osteoprotegerin, osteopontin, interferon gamma,
intercellular cell adhesion molecule 1 and vascular cell adhesion molecule 1,
systematic review suggested an increase in these biomarkers in patients with AAA.
Meta-regression analysis identified a significant positive linear correlation
between aortic diameter and CRP level. CONCLUSION: A wide variety of biomarkers
are dysregulated in patients with AAA, but their clinical value is yet to be
established. Future research should focus on the most relevant biomarkers of AAA,
and how they could be used clinically.
PMID- 25131708
TI - Educational barriers of nurses caring for sick and at-risk infants in India.
AB - AIM: To gain ideas and information from healthcare providers to optimize the
education and clinical practices of nurses caring for sick or at-risk newborns in
India. BACKGROUND: Improving infant survival has been identified as a Millennium
Development Goals; however, India still faces many challenges with 3.1 million
neonatal deaths and 2.6 million stillbirths annually. Skilled nursing care has
been associated with decreased morbidity and mortality in newborns. However, core
competencies in newborn care education and training are lacking for nurses.
METHODS: Qualitative data were collected from 12 focus groups with 101 newborn
care providers from three areas of India as well as from a 2-day stakeholders'
meeting. Data analysis was undertaken using descriptive and thematic content
analysis. RESULTS: Perceived challenges included limited manpower and high nurse
turnover, lack of access to evidence-based orientation to newborn care and
problems with access to appropriate learner-based, neonatal training. Relevant,
ongoing education opportunities, led by nursing leaders were identified to be
important solutions. CONCLUSION: Findings provide insight into the current
healthcare system in India with specific reference to the nursing care of at-risk
newborns. There is a lack of existing resources to provide standardized and
specific orientation curricula for nurses. IMPLICATIONS FOR NURSING AND HEALTH
POLICY: Policy makers in health and education need to: support and enact learner
based orientation and continuing educational opportunities as well as ongoing
competency-based education programmes; encourage nurse leader involvement and
support; and provide sustainable system-related supports. Nurses and other health
providers need to work together to influence government policy.
PMID- 25131709
TI - A descriptive qualitative study of the roles of family members in older men's
depression treatment from the perspectives of older men and primary care
providers.
AB - OBJECTIVE: The aim of this study is to describe the roles of family members in
older men's depression treatment from the perspectives of older men and primary
care physicians (PCPs). METHODS: Cross-sectional, descriptive qualitative study
conducted from 2008-2011 in primary care clinics in an academic medical center
and a safety-net county teaching hospital in California's Central Valley.
Participants in this study were the following: (1) 77 age >= 60,
noninstitutionalized men with a 1-year history of clinical depression and/or
depression treatment who were identified through screening in primary care
clinics and (2) a convenience sample of 15 PCPs from the same recruitment sites.
Semi-structured and in-depth qualitative interviews were conducted and audiotaped
then transcribed and analyzed thematically. RESULTS: Treatment-promoting roles of
family included providing an emotionally supportive home environment, promoting
depression self-management and facilitating communication about depression during
primary care visits. Treatment-impeding roles of family included triggering or
worsening men's depression, hindering depression care during primary care visits,
discouraging depression treatment and being unavailable to assist men with their
depression care. Overall, more than 90% of the men and the PCPs described one or
more treatment-promoting roles of family and over 75% of men and PCPs described
one or more treatment-impeding roles of family. CONCLUSIONS: Families play
important roles in older men's depression treatment with the potential to promote
as well as impede care. Interventions and services need to carefully assess the
ongoing roles and attitudes of family members and to tailor treatment approaches
to build on the positive aspects and mitigate the negative aspects of family
support.
PMID- 25131711
TI - Jimmy Savile: the questions for bioethics.
PMID- 25131710
TI - The proteasome inhibitor bortezomib reduced cholesterol accumulation in
fibroblasts from Niemann-Pick type C patients carrying missense mutations.
AB - Niemann-Pick disease type C (NPC) is a lipid storage disorder mainly caused by
mutations in the NPC1 gene. Approximately 60% of these mutations are missense
changes that may induce reduced NPC1 protein levels by increased degradation via
ubiquitin-proteasome. This is the case for the most prevalent worldwide mutation,
p.Ile1061Thr, as well as for other three missense changes. In the present study,
we analyzed the NPC1 levels in fibroblasts from eighteen NPC patients presenting
missense mutations. We found that fourteen of these cells lines showed decreased
levels of NPC1. Six of these cell lines were homozygous, whereas the other eight
were associated with a frame shifting mutation. We focused our attention in the
NPC homozygous samples and demonstrated that, in most of the cases, NPC1
reduction was a consequence of a decrease of its half-life. NPC cells were
treated not only with the proteasome inhibitors carbobenzoxy-l-leucyl-l-leucyl-l
leucinal or N-acetyl-leucyl-leucyl-norleucinal, both widely used as a research
tools, but also with bortezomib, the first proteasome inhibitor to reach clinical
applications, although it has never been used in NPC disease. We observed that,
after treatment, the mutant NPC1 protein levels were partially recovered in most
of the cell lines. Importantly, these mutant proteins partially recovered their
activity and substantially reduced free cholesterol levels. These results suggest
that by enhancing the NPC1 protein stability with the use of proteasome
inhibitors, their functionality might be recovered and this might represent a
therapeutical approach for future treatments of NPC disease resulting from
specific missense mutations.
PMID- 25131712
TI - Withdrawal of skeletal muscle cells from cell cycle progression triggers
differentiation of Toxoplasma gondii towards the bradyzoite stage.
AB - Toxoplasma gondii is a widespread intracellular parasite of mammals and birds and
an important opportunistic pathogen of humans. Following primary infection, fast
replicating tachyzoites disseminate within the host and either are subsequently
eliminated by the immune system or transform to latent bradyzoites which
preferentially persist in brain and muscle tissues. The factors which determine
the parasites' tissue distribution during chronic toxoplasmosis are unknown. Here
we show that mouse skeletal muscle cells (SkMCs) after differentiation to mature,
myosin heavy chain-positive, polynucleated myotubes, significantly restrict
tachyzoite replication and facilitate expression of bradyzoite-specific antigens
and tissue cyst formation. In contrast, proliferating mononuclear myoblasts and
control fibroblasts enable vigorous T. gondii replication but do not sustain
bradyzoite or tissue cyst formation. Bradyzoite formation correlates with
upregulation of testis-specific Y-encoded-like protein-2 gene expression (Tspyl2)
and p21(Waf1/Cip1 as well as downregulation of cyclin B1 and absence of DNA
synthesis, i.e. a cell cycle arrest of syncytial myotubes. Following infection
with T. gondii, myotubes but not myoblasts or fibroblasts further upregulate the
negative cell cycle regulator Tspyl2. Importantly, RNA interference-mediated
knock-down of Tspyl2 abrogates differentiation of SkMCs to myotubes and enables
T. gondii to replicate vigorously but abolishes bradyzoite-specific gene
expression and tissue cyst formation. Together, these data indicate that Tspyl2
mediated host cell cycle withdrawal is a physiological trigger of Toxoplasma
stage conversion in mature SkMCs. This finding might explain the preferred
distribution of T. gondii tissue cysts in vivo.
PMID- 25131713
TI - Development of haemostatic decontaminants for the treatment of wounds
contaminated with chemical warfare agents. 1: evaluation of in vitro clotting
efficacy in the presence of certain contaminants.
AB - The treatment of penetrating, haemorrhaging injuries sustained within a hazardous
environment may be complicated by contamination with toxic chemicals. There are
currently no specific medical countermeasures for such injuries. Haemostats with
an absorbent mechanism of action have the potential to simultaneously stop
bleeding and decontaminate wounds. However, a primary requirement of a
'haemostatic decontaminant' is the retention of clotting function in the presence
of chemical contaminants. Thus, the aim of this study was to investigate the
haemostatic efficacy of seven commercially available haemostats in the presence
of toxic chemicals (soman, VX, sulphur mustard, petrol, aviation fuel and motor
oil). Clot viscosity was assessed ex vivo using thrombelastography following
treatment of pig blood with: (i) toxic chemical; (ii) haemostat; or (iii)
haemostat in combination with toxic chemical. Several contaminants (VX, petrol
and GD) were found to be pro-haemostatic and none had an adverse effect on the
rate with which the test products attained haemostasis. However, the total clot
strength for blood treated with certain haemostats in the presence of sulphur
mustard, soman and petrol was significantly decreased. Three test products failed
to demonstrate haemostatic function in this ex vivo (thrombelastography) model;
this was tentatively ascribed to the products achieving haemostasis through a
tamponade mechanism of action, which can only be replicated using in vivo models.
Overall, this study has identified a number of commercial products that may have
potential as haemostatic decontaminants and warrant further investigation to
establish their decontaminant efficacy.
PMID- 25131714
TI - What parents want to know about the storage and use of residual newborn
bloodspots.
AB - Many state newborn screening programs retain residual newborn screening
bloodspots for a variety of purposes including quality assurance, biomedical
research, and forensic applications. This project was designed to determine the
information that prospective parents want to know about this practice. Eleven
focus groups were conducted in four states. Pregnant women and their partners and
parents of young children (N = 128) were recruited from the general public. Focus
group participants viewed two educational movies on newborn screening and DBS
retention and use. Transcripts were analyzed with qualitative methods and the
results were synthesized to identify key information items. We identified 14
categories of information from the focus groups that were synthesized into seven
items prospective parents want to know about residual DBS. The items included
details about storage, potential uses, risks and burdens, safeguards, anonymity,
return of results, and parental choice. For those state programs that retain
residual dried bloodspots, inclusion of the seven things parents want to know
about residual dried bloodspots in educational materials may improve parental
understanding, trust, and acceptance of the retention and use of stored
bloodspots.
PMID- 25131715
TI - Deciding who should get live attenuated influenza vaccine.
PMID- 25131716
TI - Sex differences in antinociceptive tolerance to delta-9-tetrahydrocannabinol in
the rat.
AB - BACKGROUND: Sex differences in cannabinoid effects have been reported in rodents,
with adult females typically being more sensitive than adult males. The present
study compared the development of antinociceptive tolerance to delta-9
tetrahydrocannabinol (THC) in adult, gonadally intact female vs. male rats.
METHODS: Cumulative dose-effect curves were obtained for THC (1.0-18 mg/kg i.p.)
on warm water tail withdrawal and paw pressure tests. Vehicle or the sex-specific
ED80 dose for THC was administered twice daily for 9 days; THC dose-effect curves
were then re-determined. RESULTS: On the pre-chronic test day, THC was
significantly more potent in females than males in producing antinociception on
the tail withdrawal and paw pressure tests. After 9 days of twice-daily THC
treatment (5.4 mg/kg/injection in females and 7.6 mg/kg/injection in males), THC
potency on both tests decreased more in females than males. On the tail
withdrawal test, chronic THC produced 4.2- vs. 2.8-fold increases in ED50 values
in females vs. males, respectively. On the paw pressure test, chronic THC
produced 4.4- vs. 2.9-fold increases in ED50 values in females vs. males,
respectively. Chronic THC treatment did not significantly disrupt estrous cycling
in females. CONCLUSIONS: These results demonstrate that--even when sex
differences in acute THC potency are controlled--females develop more
antinociceptive tolerance to THC than males. Given the importance of drug
tolerance in the development of drug dependence, these results suggest that
females may be more vulnerable than males to developing dependence after chronic
cannabinoid exposure.
PMID- 25131717
TI - Risky behavior and correlates of HIV and Hepatitis C Virus infection among people
who inject drugs in three cities in Afghanistan.
AB - BACKGROUND: Injecting drug use is the primary mode of HIV transmission and
acquisition in Afghanistan. People who inject drugs (PWID) in the country have
been characterized by high risk injecting behavior and a high burden of HCV
infection. We aimed to estimate the burden of HIV, HCV, and other infectious
diseases and to identify the correlates of HIV and HCV infection among PWID
living in three major Afghan cities in 2009. METHODS: Epidemiologic data was
collected among PWID for the integrated biological and behavioral surveillance
(IBBS) survey between May and August, 2009 in three Afghan cities. Data were
collected using a structured questionnaire and biologic specimens to screen for
HIV, HBV, HCV, syphilis, and HSV-2 using rapid testing kits. Multiple logistic
regression models were constructed to identify correlates of infection. RESULTS:
Among 548 participants, pooled HIV prevalence was 7.1% (Mazar-i-Sharif: 1.0%,
Kabul: 3.1%, Herat: 18.4%) and HCV prevalence was 40.3%. Almost all participants
with HIV infection were co-infected with HCV (94.9%). Pooled prevalence estimates
for other diseases included 7.1% for HBV, 5.5% for syphilis; and 9.3% for HSV-2.
Living in Herat, ever in prison and time injecting were independently associated
with HIV infection. Living in Kabul, Herat and time injecting were independently
associated with HCV infection. CONCLUSIONS: There is a high and heterogeneous
burden of HIV and HCV among PWID in Afghan cities. Provision of comprehensive
harm reduction services to PWID in Afghanistan is warranted to reduce exposures
associated with HIV and HCV infection, especially in the city of Herat.
PMID- 25131718
TI - A microfabricated optofluidic ring resonator for sensitive, high-speed detection
of volatile organic compounds.
AB - Advances in microanalytical systems for multi-vapor determinations to date have
been impeded by limitations associated with the microsensor technologies
employed. Here we introduce a microfabricated optofluidic ring resonator (MUOFRR)
sensor that addresses many of these limitations. The MUOFRR combines vapor
sensing and fluidic transport functions in a monolithic microstructure comprising
a hollow, vertical SiOx cylinder (250 MUm i.d., 1.2 MUm wall thickness; 85 MUm
height) with a central quasi-toroidal mode-confinement section, grown and
partially released from a Si substrate. The device also integrates on-chip
fluidic-interconnection and fiber-optic probe alignment features. High-Q
whispering gallery modes generated with a tunable 1550 nm laser exhibit rapid,
reversible shifts in resonant wavelength arising from polymer swelling and
refractive index changes as vapors partition into the ~300 nm PDMS film lining
the cylinder. Steady-state sensor responses varied in proportion to concentration
over a 50-fold range for the five organic vapors tested, providing calculated
detection limits as low as 0.5 ppm (v/v) (for m-xylene and ethylbenzene). In
dynamic exposure tests, responses to 5 MUL injected m-xylene vapor pulses were
710 ms wide and were only 18% broader than those from a reference flame
ionization detector and also varied linearly with injected mass; 180 pg was
measured and the calculated detection limit was 49 pg without use of
preconcentration or split injection, at a flow rate compatible with efficient
chromatographic separations. Coupling of this MUOFRR with a micromachined gas
chromatographic separation column is demonstrated.
PMID- 25131719
TI - Wind, water, wound, walk--do the data deliver the dictum?
AB - OBJECTIVE: To evaluate the teaching dictum "wind, water, wound, walk" in the
modern surgical environment. DESIGN: A retrospective cohort study. SETTING:
Hospitals enrolled in the American College of Surgeons National Surgical Quality
Improvement Program. PARTICIPANTS: We identified 11,137 patients enrolled in
American College of Surgeons National Surgical Quality Improvement Program
Participant Use File (2011) who were older than 18 years; underwent a general
surgical procedure; and developed a postoperative pneumonia (PNA, "wind"),
urinary tract infection (UTI, "water"), surgical site infection (SSI, "wound"),
or venous thromboembolic event (VTE, "walk") for inclusion in the study. Patients
were excluded if they had an infection present at the time of surgery or were
missing information on the time of diagnosis. RESULTS: The median day of
diagnosis differed significantly according to occurrence type (median day of PNA
= 5, UTI = 8, SSI = 11, and VTE = 9, p < 0.001). The sequence of occurrences
diagnosed before discharge (median day of PNA = 4, UTI = 5, SSI = 7, and VTE = 5)
differed from that of occurrences diagnosed following discharge (median day of
PNA = 10, UTI = 14, SSI = 14, and VTE = 14). Within the predischarge and
postdischarge subsets, the median day of diagnosis remained significantly
different according to occurrence type (all p's < 0.001). CONCLUSIONS: The dictum
should be taught as, "wind, water, walk, wound" to reflect the timing and
progression of the diagnosis of PNA, UTI, VTE, and SSI. The dictum did not
reflect the timing or sequence of the occurrences in the cohort diagnosed after
discharge. Educators must teach trainees to apply the dictum in the appropriate
patient setting. As surgical care changes, we must continue to reassess our
educational pearls to ensure that they reflect the modern reality.
PMID- 25131721
TI - Impact of hepatitis C virus infection on the risk of death of alcohol-dependent
patients.
AB - Hepatitis C virus (HCV) infection is frequent among patients with alcohol use
disorders. We aimed to analyse the impact of HCV infection on survival of
patients seeking treatment for alcohol use. This was a longitudinal study in a
cohort of patients who abused alcohol recruited in two detoxification units.
Socio-demographic and alcohol use characteristics, liver function tests for the
assessment of alcohol-related liver disease and HCV and HIV infection serologies
were obtained at admission. Patients were followed until December 2008; causes of
death were ascertained through clinical records and death registry. Cox models
were used to analyse predictors of death. A total of 675 patients (79.7% men)
were admitted; age at admission was 43.5 years (IQR: 37.9-50.2 years), duration
of alcohol abuse was 18 years (IQR: 11-24 years), and median alcohol consumption
was 200 g/day (IQR: 120-275 g/day). Distribution of patients according to viral
infections was as follows: 75.7% without HCV or HIV infection, 14.7% HCV
infection alone and 8.1% HCV/HIV coinfection. Median follow-up was 3.1 years
(IQR: 1.5-5.1 years) accounting for 2,345 person-years. At the end of study, 78
patients (11.4%) had died. In the multivariate analysis, age at admission (HR =
1.71, 95%CI: 1.05-2.80), alcohol-related liver disease (HR = 3.55, 95%CI: 1.93
6.53) and HCV/HIV co-infection (HR = 3.86 95%CI: 2.10-7.11) were predictors of
death. Younger patients (<=43 years) with HCV infection were more likely to die
than those without viral infections (HR = 3.1, 95%CI: 1.3-7.3; P = 0.007). Among
patients with alcohol-related liver disease, mortality rate was high,
irrespective of viral infections. These data show that HCV infection confers a
worse prognosis in patients with alcohol use disorders.
PMID- 25131720
TI - The role of IL-28, IFN-gamma, and TNF-alpha in predicting response to pegylated
interferon/ribavirin in chronic HCV patients.
AB - The primary goal of HCV therapy is to achieve a sustained virological response
(SVR). Many host and viral factors influence the treatment response. Cytokines
play an important role in the defense against viral infections, where successful
treatment of hepatitis C depends on a complex balance between pro- and anti
inflammatory responses. In the present study, we investigated the relationship
between the presence and percentage of some cytokines (IL-28, IFN-gamma, and TNF
alpha) regarding different clinicopathological parameters including response to
therapy in chronic HCV patients using immunohistochemical technique. This study
was carried out on 64 chronic HCV patients (34 responders and 30 non-responders).
Of cases, 54% showed IL-28 expression, which was associated with low AST (p =
0.002) and low HAI score (p = 0.006). Of cases, 67 and 45% showed IFN-gamma and
TNF-alpha expression, respectively, where the median percentage of TNF-alpha
expression was higher in grade II spotty necrosis compared to grade I. Some
inflammatory cytokines expressed by intrahepatic inflammatory cells in chronic
HCV patients promote inflammation and injury (pro-inflammatory) such as TNF
alpha. Other cytokines aid in resolving inflammation and injury (anti
inflammatory) such as IL-28. The balance between these cytokines will determine
the degree of inflammatory state. None of the investigated cytokines proved its
clear cut role in affecting response to therapy, however, their levels varied
between responders and non-responders for further investigations to clarify.
PMID- 25131722
TI - Quantifying histone and RNA polymerase II post-translational modification
dynamics in mother and daughter cells.
AB - Post-translational histone modifications are highly correlated with
transcriptional activity, but the relative timing of these marks and their
dynamic interplay during gene regulation remains controversial. To shed light on
this problem and clarify the connections between histone modifications and
transcription, we demonstrate how FabLEM (Fab-based Live Endogenous Modification
labeling) can be used to simultaneously track histone H3 Lysine 9 acetylation
(H3K9ac) together with RNA polymerase II Serine 2 and Serine 5 phosphorylation
(RNAP2 Ser2ph/Ser5ph) in single living cells and their progeny. We provide a
detailed description of the FabLEM methodology, including helpful tips for
preparing and loading fluorescently conjugated antigen binding fragments (Fab)
into cells for optimal results. We also introduce simple procedures for analyzing
and visualizing FabLEM data, including color-coded scatterplots to track
correlations between modifications through the cell cycle and temporal cross
correlation analysis to dissect modification dynamics. Using these methods, we
find significant correlations that span cell generations, with a relatively
strong correlation between H3K9ac and Ser5ph that appears to peak a few hours
before mitosis and may reflect the bookmarking of genes for efficient re
initiation following mitosis. The techniques we have developed are broadly
applicable and should help clarify how histone modifications dynamically
contribute to gene regulation.
PMID- 25131723
TI - Moonlighting proteins as virulence factors of pathogenic fungi, parasitic
protozoa and multicellular parasites.
AB - The delicate balance between eukaryotic pathogens and their human hosts during
the initiation and development of infection is a complex process involving many
diverse interactions. Different infectious agents, including pathogenic fungi,
parasitic protozoa and multicellular parasites, directly interact through their
cell surface with epithelial or endothelial cells of the human host as well as
various proteinaceous host ligands such as extracellular matrix or plasma
proteins. Eukaryotic pathogens possess a number of virulence factors but a
relatively recently recognized and particularly interesting group of factors
capable of enhancing virulence is the set of so-called 'moonlighting proteins'.
This term was coined for a relatively large collection of housekeeping enzymes
lacking special targeting motifs that would determine their extracellular
localization, but that are often present at the cell surface of pathogen. Several
such enzymes with key metabolic functions in glycolysis, the pentose phosphate
cycle or other fundamental intracellular processes perform entirely new, non
catalytic roles often associated with adhesion to host ligands. Our current study
summarizes some of the current knowledge of interesting moonlighting proteins
which play putative or confirmed roles as virulence factors in pathogenic fungi,
parasitic protozoa and multicellular parasites.
PMID- 25131724
TI - Quantification and genotyping of lipoprotein lipase in patients with diabetic
lipaemia.
AB - AIMS: To determine if diabetic lipaemia is caused by loss of function mutations
in the lipoprotein lipase gene, LPL. METHODS: We conducted a case-control study
over 2 years in two tertiary care hospitals in South Australia. Six patients with
a history of diabetic lipaemia and 12 control subjects, with previous diabetic
ketoacidosis and peak triglyceride concentrations < 2.4 mmol/l were included.
Participants were well at the time of study investigations. RESULTS: Only one
patient with lipaemia had a loss of function mutation in LPL and no functional
mutations in APOC2 or GPIHBP1 were identified. The mean lipoprotein lipase
concentration was lower in patients with diabetic lipaemia than in control
subjects (306 vs. 484 MUg/l, P = 0.04). The mean fasting C-peptide concentration
was higher in patients with diabetic lipaemia than in control subjects (771 vs.
50 pmol/l; P = 0.001). CONCLUSIONS: Lipoprotein lipase deficiency in patients
with a history of diabetic lipaemia was predominantly quantitative, rather than
secondary to mutations in LPL, APOC2 or GPIHBP1. The majority of patients with
severe hypertriglyceridaemia in diabetic ketoacidosis may have ketosis-prone Type
2, rather than Type 1, diabetes.
PMID- 25131725
TI - A novel CYLD germline mutation in Brooke-Spiegler syndrome.
AB - BACKGROUND: Brooke-Spiegler syndrome (BSS) is a rare, inherited, autosomal
dominant disorder characterized by the development of multiple adnexal neoplasms
including spiradenomas, cylindromas, trichoepitheliomas and major and minor
salivary glands neoplasms. This syndrome encompasses a wide variability of
clinical phenotypes depending on the variable number of tumours present in the
given patient. OBJECTIVE: Somatic mutations in adjunct to CYLD germline mutations
may play a central role in the development of the tumour phenotype and in the
genotype-phenotype correlations. METHODS: Blood sample and paraffin embedded
tissue biopsied from three cylindromas, one trichoepithelioma and one
spiradenomas were collected after obtaining informed consent from our patient and
genomic DNA was isolated. RESULTS: We found out a novel germline mutation in the
CYLD gene in exon 15 that resulted in the deletion of one nucleotide. This gives
rise to a premature translational termination codon at amino acid position 693
prior to four Cys-X-X-Cys pairs and one of the two catalytic domains of ubiquitin
carboxy-terminal hydrolases. In only one cylindroma we detected the same germline
mutation (c.2070delT/p.F690FfsX3) in addition to two somatic events (I645V and
R936X). The presence of this unique mutation could be linked to the peculiar
phenotype of our patient who presented an attenuated form of BSS, an autosomal
dominant inheritance with low penetrance and no additional visceral tumours.
CONCLUSIONS: The overall phenotype of our patient may support the hypothesis that
somatic mutations in adjunct to CYLD germline mutations may play a central role
in the development of the tumour phenotype and in the genotype-phenotype
correlations.
PMID- 25131727
TI - Technology transfer and scale-up of the Flublok recombinant hemagglutinin (HA)
influenza vaccine manufacturing process.
AB - Multiple different hemagglutinin (HA) protein antigens have been reproducibly
manufactured at the 650L scale by Protein Sciences Corporation (PSC) based on an
insect cell culture with baculovirus infection. Significantly, these HA protein
antigens were produced by the same Universal Manufacturing process as described
in the biological license application (BLA) for the first recombinant influenza
vaccine approved by the FDA (Flublok). The technology is uniquely designed so
that a change in vaccine composition can be readily accommodated from one HA
protein antigen to another one. Here we present a vaccine candidate to combat the
recently emerged H7N9 virus as an example starting with the genetic sequence for
the required HA, creation of the baculovirus and ending with purified protein
antigen (or vaccine component) at the 10L scale accomplished within 38 days under
GMP conditions. The same process performance is being achieved at the 2L, 10L,
100L, 650L and 2500L scale. An illustration is given of how the technology was
transferred from the benchmark 650L scale facility to a retrofitted microbial
facility at the 2500L scale within 100 days which includes the time for facility
engineering changes. The successful development, technology transfer and scale-up
of the Flublok process has major implications for being ready to make vaccine
rapidly on a worldwide scale as a defense against pandemic influenza. The
technology described does not have the same vulnerability to mutations in the egg
adapted strain, and resulting loss in vaccine efficacy, faced by egg based
manufacture.
PMID- 25131726
TI - Assessing the feasibility of hepatitis C virus vaccine trials: results from the
Hepatitis C Incidence and Transmission Study-community (HITS-c) vaccine
preparedness study.
AB - Efficacy trials of preventive hepatitis C virus (HCV) vaccine candidates raise
challenging scientific and ethical issues. Based on data from the first 3 years
of a community-based prospective observational study - the Hepatitis C Incidence
and Transmission Study-community (HITS-c) - this paper examines the feasibility
of conducting trials of candidate HCV vaccines with people who inject drugs
(PWID) in Sydney, Australia. Of the 166 PWID confirmed HCV antibody negative and
eligible for enrolment, 156 (94%) completed baseline procedures. Retention was
high, with 89% of participants retained at 48 weeks and 76% of participants
completing at least 75% of study visits within 2 weeks of schedule. The rate of
primary HCV infection was 7.9/100 py (95% CI 4.9, 12.7). Of the 17 incident
cases, 16 completed at least one follow-up assessment and 12 (75%) had evidence
of chronic viraemia with progression to chronic HCV infection estimated to be
6/100 py. Power calculations suggest a chronic HCV infection rate of at least
12/100 py (primary HCV infection rate 16/100 py) will be required for stand-alone
trials of highly efficacious candidates designed to prevent chronic infection.
However, elevated primary HCV infection was observed among participants not
receiving opioid substitution therapy who reported heroin as the main drug
injected (26.9/100 py, 95% CI 14.5, 50.0) and those who reported unstable housing
(23.5/100 py, 95% CI 7.6, 72.8), daily or more frequent injecting (22.7/100 py,
95% CI 12.2, 42.2) and receptive syringe sharing (23.6/100 py, 95% CI 9.8, 56.7)
in the 6 months prior to baseline. These data suggest that it is possible to
recruit and retain at-risk PWID who adhere to study protocols and that
modification of eligibility criteria may identify populations with sufficiently
high HCV incidence. Results support the feasibility of large multi-centre HCV
vaccine trials, including in the Australian setting.
PMID- 25131728
TI - Characterization and immunogenicity in mice of recombinant influenza
haemagglutinins produced in Leishmania tarentolae.
AB - The membrane displayed antigen haemagglutinin (HA) from several influenza strains
were expressed in the Leishmania tarentolae system. This non-conventional
expression system based on a parasite of lizards, can be readily propagated to
high cell density (>10(8)cells/mL) in a simple incubator at 26 degrees C. The
genes encoding HA proteins were cloned from six influenza strains, among these
being a 2009 A/H1N1 pandemic strain from swine origin, namely
A/California/07/09(H1N1). Soluble HA proteins were secreted into the cell culture
medium and were easily and successfully purified via a His-Tag domain fused to
the proteins. The overall process could be conducted in less than 3 months and
resulted in a yield of approximately 1.5-5mg of HA per liter of biofermenter
culture after purification. The recombinant HA proteins expressed by L.
tarentolae were characterized by dynamic light scattering and were observed to be
mostly monomeric. The L. tarentolae recombinant HA proteins were immunogenic in
mice at a dose of 10MUg when administered twice with an oil-in-water emulsion
based adjuvant. These results suggest that the L. tarentolae expression system
may be an alternative to the current egg-based vaccine production.
PMID- 25131729
TI - Effect of multiple, simultaneous vaccines on polio seroresponse and associated
health outcomes.
AB - BACKGROUND: Administration of multiple simultaneous vaccines to infants,
children, and military recruits is not uncommon. However, little research exists
to examine associated serological and health effects, especially in adults.
METHOD: We retrospectively examined 416 paired serum specimens from U.S. military
subjects who had received the inactivated polio vaccine (IPV) alone or in
combination with either 1 other vaccine (<3 group) or 4 other vaccines (>4
group). Each of the 2 groups was subdivided into 2 subgroups in which Tdap was
present or absent. RESULTS: The >4 group was associated with a higher proportion
of polio seroconversions than the <3 group (95% vs. 58%, respectively, p<0.01).
Analysis of the <3 subgroup that excluded Tdap vs. the >4 subgroup that excluded
Tdap showed no difference between them (p>0.1). However, the >4 subgroup that
included Tdap had significantly more seroconversions than either the <3 subgroup
that excluded Tdap or the >4 subgroup that excluded Tdap (p<0.01). Overall, at
least 98% of subjects were at or above the putative level of seroprotection both
pre- and post-vaccination, yet at least 81% of subjects seroconverted. In an
analysis of 400 of the subjects in which clinic in- and outpatient encounters
were counted over the course of 1 year following vaccinations, there was no
significant difference between the 2 groups (p>0.1). CONCLUSION: A combination of
>4 vaccines including IPV appeared to have an immunopotentiation effect on polio
seroconversion, and Tdap in particular was a strong candidate for an important
role. The dose of IPV we studied in our subjects, who already had a high level of
seroprotection, acted as a booster. In addition, there appear to be no negative
health consequences from receiving few versus more multiple simultaneous
vaccinations.
PMID- 25131730
TI - TLR7/8 agonists activate a mild immune response in rabbits through TLR8 but not
TLR7.
AB - Toll-like receptors 7 (TLR7) and 8 (TLR8) recognize viral single-stranded RNA and
small molecular weight agonists to activate anti-viral immune responses. TLR8s
from different species have distinct ligand recognitions. For example, human TLR8
is responsive to ligand stimulation, but mouse and rat TLR8 are activated by
small molecular weight agonists only in the presence of polyT
oligodeoxynucleotides. TLR7 and TLR8 have been reported to be absent and
pseudogenized, respectively, in rabbit (Oryctolagus cuniculus). In this study, we
detected the expression of rabbit (rab)TLR8 in immune-cell-associated tissues.
Cell proliferation and cytokine expressions in rabbit splenocytes were induced by
the TLR7/8 ligand but not by the TLR7 ligands, suggesting that rabTLR8 is
functional but rabTLR7 is not. In rabbits, CL075, a TLR7/8 ligand, activated an
antigen-specific antibody response, although one not as potent as aluminum salt
or Freund's adjuvant. Nevertheless, CL075, alone or in combination with aluminum
salt, generates fewer adverse effects than Freund's adjuvant at the injection
sites. To further investigate the activation of rabTLR8, we cloned its cDNA. In
cell-based assay, this rabTLR8 is activated by TLR7/8 ligand but not activated by
TLR7 ligand. Upon stimulation the rabTLR8 had a lower activation compared to the
activation of TLR8 from other species, except the mouse and rat TLR8s. Using
different deletion and human-rabbit chimeric TLR8 expressing constructs, we
showed that an extra peptide in the undefined region results in reduced activity
of rabTLR8. These results provide a molecular basis for the mild activities of
TLR7/8 ligands in rabbits, and suggest TLR7/8 agonists may provide safer immune
stimuli in rabbits than in other non-rodent species.
PMID- 25131731
TI - Activation of dendritic cell function by soypeptide lunasin as a novel vaccine
adjuvant.
AB - The addition of an appropriate adjuvant that activates the innate immunity is
essential to subsequent development of the adaptive immunity specific to the
vaccine antigens. Thus, any innovation capable of improving the immune responses
may lead to a more efficacious vaccine. We recently identified a novel immune
modulator using a naturally occurring seed peptide called lunasin. Lunasin was
originally isolated from soybeans, and it is a small peptide containing 43 amino
acids. Our studies revealed stimulatory effects of lunasin on innate immune cells
by regulating expression of a number of genes that are important for immune
responses. The objective was to define the effectiveness of lunasin as an
adjuvant that enhances immune responses. The immune modulating functions of
lunasin were characterized in dendritic cells (DCs) from human peripheral blood
mononuclear cells (PBMCs). Lunasin-treated conventional DCs (cDCs) not only
expressed elevated levels of co-stimulatory molecules (CD86, CD40) but also
exhibited up-regulation of cytokines (IL1B, IL6) and chemokines (CCL3, CCL4).
Lunasin-treated cDCs induced higher proliferation of allogeneic CD4+ T cells when
comparing with medium control treatment in the mixed leukocyte reaction (MLR).
Immunization of mice with ovalbumin (OVA) and lunasin inhibited the growth of OVA
expressing A20 B-lymphomas, which was correlated with OVA-specific CD8+ T cells.
In addition, lunasin was an effective adjuvant for immunization with OVA, which
together improved animal survival against lethal challenge with influenza virus
expressing the MHC class I OVA peptide SIINFEKL (PR8-OTI). These results suggest
that lunasin may function as a vaccine adjuvant by promoting DC maturation, which
in turn enhances the development of protective immune responses to the vaccine
antigens.
PMID- 25131732
TI - Economic evaluation of meningococcal serogroup B childhood vaccination in
Ontario, Canada.
AB - OBJECTIVE: Invasive Neisseria meningitidis serogroup B (MenB) disease is a low
incidence but severe infection (mean annual incidence 0.19/100,000/year, case
fatality 11%, major long-term sequelae 10%) in Ontario, Canada. This study
assesses the cost-effectiveness of a novel MenB vaccine from the Ontario
healthcare payer perspective. METHODS: A Markov cohort model of invasive MenB
disease based on high quality local data and data from the literature was
developed. A 4-dose vaccination schedule, 97% coverage, 90% effectiveness, 66%
strain coverage, 10-year duration of protection, and vaccine cost of C$75/dose
were assumed. A hypothetical Ontario birth cohort (n=150,000) was simulated to
estimate expected lifetime health outcomes, quality-adjusted life years (QALYs),
and costs, discounted at 5%. RESULTS: A MenB infant vaccination program is
expected to prevent 4.6 invasive MenB disease cases over the lifetime of an
Ontario birth cohort, equivalent to 10 QALYs gained. The estimated program cost
of C$46.6 million per cohort (including C$318,383 for treatment of vaccine
associated adverse events) were not offset by healthcare cost savings of
C$150,522 from preventing MenB cases, resulting in an incremental cost of C$4.76
million per QALY gained. Sensitivity analyses showed the findings to be robust.
CONCLUSIONS: An infant MenB vaccination program significantly exceeds commonly
used cost-effectiveness thresholds and thus is unlikely to be considered
economically attractive in Ontario and comparable jurisdictions.
PMID- 25131733
TI - The muscle findings in a pediatric patient with live attenuated oral polio
vaccine-related flaccid monoplegia.
AB - A pediatric patient, who was given live-attenuated oral polio vaccine twice
without distinct gait disturbance during infancy, begun to present limp at 3
years. His gait disturbance became remarkable with aging. At 7 years, he was
unable to dorsiflex the left ankle, and presented flaccid monoplegia of the left
lower extremity, and the left Achilles tendon reflex was diminished. Magnetic
resonance imaging revealed multiple crack-lines in the left anterior tibial
muscle, but was unable to detect any distinct lesion at responsible level of L4,
L5 and S1 anterior horn cells' degeneration. Electromyography showed continuous
fibrillation potentials, but muscle biopsy presented nearly normal in this
muscle. The serum levels of polio antibody type 1 and type 2 titers were elevated
64* respectively, while the type 3 antibody titer was not elevated 4*. This
patient was diagnosed as live attenuated oral polio vaccine-related flaccid
monoplegia, with mild clinical course.
PMID- 25131734
TI - Reactogenicity and immunogenicity of inactivated poliovirus vaccine produced from
Sabin strains: a phase I Trial in healthy adults in Cuba.
AB - BACKGROUND: To ensure that developing countries have the option to produce
inactivated poliovirus vaccine (IPV), the Global Polio Eradication Initiative has
promoted the development of an IPV using Sabin poliovirus strains (Sabin IPV).
This trial assessed the reactogenicity and immunogenicity of Sabin IPV and
adjuvanted Sabin IPV in healthy adults in Cuba. METHODS: This is a randomized,
controlled phase I trial, enrolling 60 healthy (previously vaccinated) male human
volunteers, aged 19-23 years to receive one dose of either Sabin IPV (20:32:64
DU/dose), adjuvanted Sabin IPV (10:16:32 DU/dose), or conventional Salk IPV
(40:8:32 DU/dose). The primary endpoint for reactogenicity relied on monitoring
of adverse events. The secondary endpoint measured boosting immune responses
(i.e. seroconversion or 4-fold rise) of poliovirus antibody, assessed by
neutralization assays. RESULTS: Sixty subjects fulfilled the study requirements.
No serious adverse events reported were attributed to trial interventions during
the 6-month follow-up period. Twenty-eight days after vaccination, boosting
immune responses against poliovirus types 1-3 were between 90% and 100% in all
vaccination groups. There was a more than 6-fold increase in median antibody
titers between pre- and post-vaccination titers in all vaccination groups.
DISCUSSION: Both Sabin IPV and adjuvanted Sabin IPV were well tolerated and
immunogenic against all poliovirus serotypes. This result suggests that the
aluminum adjuvant may allow a 50% (or higher) dose reduction.
PMID- 25131736
TI - Natural killer cell responses to dendritic cells infected by the ANRS HIV-1
vaccine candidate, MVAHIV.
AB - Innate mechanisms are critical for the development of the host immune responses
to antigen. Particularly, early interaction between natural killer (NK) cells and
dendritic cells (DC) greatly impacts the establishment of both innate and
adaptive immune responses. In this study, using an autologous in vitro co-culture
system we analyzed the NK cell response against MVAHIV-infected DC as well as the
subsequent ability of these MVAHIV-primed NK cells to control HIV-1 infection in
autologous DC. We found that NK cells responded early to MVAHIV- or MVAWT
infected DC in terms of degranulation and cytokine production. After a 4-day
priming of NK cells by MVAHIV- or MVAWT-infected DC we observed an enhanced
proliferation and modulation in the NK cell receptor repertoire expression.
Interestingly, we found that MVAHIV-primed NK cells had a significant higher
ability to control HIV-1 infection in autologous DC compared to MVAWT-primed NK
cells; and this enhanced anti-HIV-1 activity appeared to be HIV-specific as
MVAHIV-primed NK cells did not have a better ability to control other viral
infections or respond against tumoral cells. Furthermore, we observed that NK
cell receptors NKG2D and NKp46 modulate the priming of NK cells. This data
provides evidence that in vitro NK cells can be primed by viral vector-infected
DC, in the context of a NK/DC culture, to specifically target viral infected
cells.
PMID- 25131737
TI - Intradermal and virosomal influenza vaccines for preventing influenza
hospitalization in the elderly during the 2011-2012 influenza season: a
comparative effectiveness study using the Valencia health care information
system.
AB - BACKGROUND: The use of intradermal vaccination or virosomal vaccines could
increase protection against influenza among the vulnerable population of older
adults. Studies assessing the comparative effectiveness of these two influenza
vaccine types in this age group are lacking. METHODS: We conducted a
retrospective cohort study to estimate the comparative effectiveness of
intradermal seasonal trivalent-influenza vaccine (TIV) delivered by a microneedle
injection system and a virosomal-TIV intramuscularly delivered for prevention of
influenza hospitalization in non-institutionalized adults aged >=65 years. We
obtained administrative data on immunization status and influenza hospitalization
for the 2011-2012 influenza season, and used Cox regression models to assess
comparative effectiveness. We estimated crude and adjusted (age, sex,
comorbidity, pharmaceutical claims, recent pneumococcal vaccination and number of
hospitalizations for all causes other than influenza between the previous and
current influenza seasons) hazard ratios (HR). RESULTS: Overall, 164,021
vaccinated subjects were evaluated. There were 127 hospitalizations for influenza
among 62,058 subjects, contributing 914,740 person-weeks at risk in the virosomal
TIV group, and 133 hospitalizations for influenza among 101,963 subjects,
contributing 1,504,570 person-weeks at risk in the intradermal-TIV group. The
crude HR of intradermal-TIV relative to virosomal-TIV was 0.64 (95% confidence
interval (CI): 0.50-0.81), and the adjusted Cox estimated HR was 0.67 (95% CI:
0.52-0.85). CONCLUSIONS: During the 2011-2012 influenza season the risk of
hospitalization for influenza was reduced by 33% in non-institutionalized elderly
adults who were vaccinated with intradermal-TIV compared with virosomal-TIV.
PMID- 25131738
TI - Chronic helminth infections impair pneumococcal vaccine responses.
AB - Pneumonia is the leading killer of children and disproportionately affects
developing countries. Vaccination campaigns against Streptococcus pneumoniae, the
leading cause of pneumonia, have recently been launched with a new conjugate
vaccine in Africa. Using a mouse model, we assessed the potential role that the
high burden of helminth infections in the countries targeted for vaccine might
have on vaccine effectiveness. Mice vaccinated with either commercial conjugate
or purified polysaccharide vaccines had impaired antibody responses if they were
chronically infected with Taenia crassiceps. This translated to increased
susceptibility to pneumococcal pneumonia and high mortality compared to helminth
negative vaccinated animals, which were fully protected from disease and death.
Antibodies taken from Taenia-infected, vaccinated mice were unable to effectively
opsonize S. pneumoniae for killing by alveolar macrophages, and did not protect
against pneumococcal challenge when adoptively transferred into naive animals.
These data may have implications for vaccination programs in countries endemic
with helminths.
PMID- 25131735
TI - Interaction between neonatal vitamin A supplementation and timing of measles
vaccination: a retrospective analysis of three randomized trials from Guinea
Bissau.
AB - BACKGROUND: In Guinea-Bissau we conducted three trials of neonatal vitamin A
supplementation (NVAS) from 2002 to 2008. None of the trials found a beneficial
effect on mortality. From 2003 to 2007, an early measles vaccine (MV) trial was
ongoing, randomizing children 1:2 to early MV at 4.5 months or no early MV, in
addition to the usual MV at 9 months. We have previously found interactions
between vitamin A and vaccines. OBJECTIVE: We investigated whether there were
interactions between NVAS and early MV. DESIGN: We compared the mortality of NVAS
and placebo recipients: first, from 4.5 to 8 months for children randomized to
early MV or no early MV; and second, from 9 to 17 months in children who had
received two MV or one MV. Mortality rates (MR) were compared in Cox models
producing mortality rate ratios (MRR). RESULTS: A total of 5141 children were
randomized to NVAS (N=3015) or placebo (N=2126) and were later randomized to
early MV (N=1700) or no early MV (N=3441). Between 4.5 and 8 months, NVAS
compared with placebo was associated with higher mortality in early MV recipients
(MR=30 versus MR=0, p=0.01), but not in children who did not receive early MV (p
for interaction between NVAS and early MV=0.03). From 9 to 17 months NVAS was not
associated with mortality. Overall, from 4.5 to 17 months NVAS was associated
with increased mortality in early MV recipients (Mortality rate ratio=5.39 (95%
confidence interval: 1.62, 17.99)). CONCLUSIONS: These observations indicate that
NVAS may interact with vaccines given several months later. This may have
implications for the planning of future child intervention programs.
PMID- 25131739
TI - Utilization of administrative data to assess the association of an adolescent
health check-up with human papillomavirus vaccine uptake in Germany.
AB - BACKGROUND: In Germany, 3-dose human papillomavirus (HPV) vaccination is
recommended for 12-17 year-old females. Countrywide monitoring of HPV vaccination
coverage (VC) does not exist, but small-scale surveys suggested suboptimal
uptake. There is currently no concerted implementation strategy in place, and
approaches for improved vaccine delivery are needed. Our objectives were to
analyze health insurance claims data to estimate HPV VC in the target population
and to assess the association of the routine adolescent health check-up 'J1'
(offered to 12-14 year-olds) with HPV vaccine uptake. METHODS: We sampled a
subset of 12-16 year-old females from claims data in 15 of the 16 German federal
states. Sampling was based on documented physician contacts flanking the follow
up period 2008-2012. We reconstructed age- and region-stratified histories of
individual-level HPV vaccination series and J1 utilization and calculated country
level estimates. RESULTS: The study sample represented 54% (n=1.04 million) of
the total target population. VC estimates for starting (and completing) HPV
vaccination series ranged from 6.1% (1.2%) among 12-year-olds to 47.6% (36.2%)
among 16-year-olds. J1 utilization was 50% at maximum. In J1-attendees, 42.0% had
received >=1 vaccine doses, translating into a significant association of J1
utilization and vaccine uptake with a 6.9-fold higher likelihood in 12-year-olds
and 1.4-fold higher likelihood in 16-year-olds of receiving HPV vaccination.
CONCLUSION: HPV VC in Germany is low. Adolescent check-up J1 is associated with
increased and accelerated HPV vaccine uptake securing immunization before sexual
debut and should be used as a tool to improve VC in the target population.
However, J1 utilization is only moderate and more than half of attendees had not
received HPV vaccination, which represents a substantial proportion of missed
opportunities. This indicates that J1 needs both further promotion through
legislative structures already in place for other health check-ups and more
awareness as an opportunity to offer HPV vaccinations.
PMID- 25131740
TI - Studies on recombinant glucokinase (r-glk) protein of Brucella abortus as a
candidate vaccine molecule for brucellosis.
AB - Brucellosis is one of the most prevalent zoonotic diseases of worldwide
distribution caused by the infection of genus Brucella. Live attenuated vaccines
such as B. abortus S19, B. abortus RB51 and B. melitensis Rev1 are found most
effective against brucellosis infection in animals, contriving a number of
serious side effects and having chances to revert back into their active
pathogenic form. In order to engineer a safe and effective vaccine candidate to
be used in both animals and human, a recombinant subunit vaccine molecule
comprising the truncated region of glucokinase (r-glk) gene from B. abortus S19
was cloned and expressed in Escherichia coli BL21DE3 host. Female BALB/c mice
immunized with purified recombinant protein developed specific antibody titer of
1:64,000. The predominant IgG2a and IgG2b isotypes signified development of Th1
directed immune responses. In vitro cell cytotoxicity assay using anti-r-glk
antibodies incubated with HeLa cells showed 81.20% and 78.5% cell viability
against lethal challenge of B. abortus 544 and B. melitensis 16M, respectively.
The lymphocyte proliferative assay indicated a higher splenic lymphocyte
responses at 25MUg/ml concentration of protein which implies the elevated
development of memory immune responses. In contrast to control, the immunized
group of mice intra-peritoneal (I.P.) challenged with B. abortus 544 were
significantly protected with no signs of necrosis and vacuolization in their
liver and spleen tissue. The elevated B-cell response associated with Th1 adopted
immunity, significant in vitro cell viability as well as protection afforded in
experimental animals after challenge, supplemented with histopathological
analysis are suggestive of r-glk protein as a prospective candidate vaccine
molecule against brucellosis.
PMID- 25131741
TI - The incidence of pediatric invasive Haemophilus influenzae and pneumococcal
disease in Chiba prefecture, Japan before and after the introduction of conjugate
vaccines.
AB - The Haemophilus influenzae type b (Hib) vaccine and the heptavalent pneumococcal
conjugate vaccine (PCV7) were introduced in Japan in 2008 and 2010, respectively.
In 2011, immunization with these two vaccines was encouraged throughout Japan
through a governmental program. Children treated in Chiba prefecture for culture
proven invasive H. influenzae disease (IHiD) and invasive Streptococcus
pneumoniae disease (IPD) were identified in a prefectural surveillance study from
2008 to 2013. The incidence rate ratio (IRR) and its confidence interval (CI)
were calculated to compare the 3 years before and after governmental financial
support for vaccination. The average number of IHiD and IPD cases among children
<5 years of age in 2011-2013 decreased 84% (IRR: 0.16, 95% CI: 0.09-0.26,
p<0.0001) and 51% (IRR: 0.49, 95% CI: 0.37-0.63, p<0.0001) compared with those
occurring in 2008-2010. The most common non-PCV7 serotype encountered in 2011 and
2013 was 19A. After governmental subsidization of Hib and PCV7 vaccination, IHiD
and IPD decreased in Chiba prefecture, Japan. Continuous surveillance is
necessary to determine the effectiveness of these two vaccines and for detection
of emerging invasive serotypes.
PMID- 25131742
TI - Influenza vaccination in HIV-infected individuals: systematic review and
assessment of quality of evidence related to vaccine efficacy, effectiveness and
safety.
AB - BACKGROUND: Influenza infection in HIV-infected individuals is associated with
increased severity of illness. We performed a systematic review of the available
evidence on efficacy, effectiveness and safety of seasonal influenza vaccination
in HIV-infected individuals. DESIGN: Systematic review, meta-analysis and
assessment of evidence quality. METHODS: Using a previous systematic review as
starting point, we searched MEDLINE, EMBASE and Cochrane data base for studies on
efficacy, effectiveness or safety of trivalent inactivated influenza vaccines
(TIV) in HIV-infected individuals. Evidence quality was assessed for each outcome
using the GRADE methodology. RESULTS: Three randomized-controlled trials and
three cohort studies were identified, including a total of 1562 HIV-infected
individuals. In adults, TIV prevented laboratory-confirmed influenza with a
pooled efficacy of 85% (95% CI, 22-97%) (evidence quality: moderate), but no
significant effects on other clinical outcomes were observed (evidence quality:
moderate to low). One cohort study showed an effectiveness of 71% (95% CI, 44
85%) for prevention of laboratory-confirmed influenza, whereas no effect on
influenza-like illness was found. However, risk of bias was high in all
observational studies. In children aged 6-59 months, efficacy of TIV in
preventing laboratory-confirmed influenza was 11% (95% CI, -30 to 54%) (evidence
quality: moderate). Regarding other endpoints, no statistically significant
effects were reported (evidence quality: moderate to low). No severe adverse
events following influenza vaccination were observed in these studies.
CONCLUSION: This systematic review indicates that TIV is effective in preventing
influenza infection in HIV-infected adults but not in young children. For both
age-groups, only limited evidence exists for other outcomes, indicating a need
for further studies.
PMID- 25131743
TI - Comparing the cost-effectiveness of two- and three-dose schedules of human
papillomavirus vaccination: a transmission-dynamic modelling study.
AB - BACKGROUND: Recent evidence suggests that two doses of HPV vaccines may be as
protective as three doses in the short-term. We estimated the incremental cost
effectiveness of two- and three-dose schedules of girls-only and girls & boys HPV
vaccination programmes in Canada. METHODS: We used HPV-ADVISE, an individual
based transmission-dynamic model of multi-type HPV infection and diseases
(anogenital warts, and cancers of the cervix, vulva, vagina, anus, penis and
oropharynx). We conducted the analysis from the health payer perspective, with a
70-year time horizon and 3% discount rate, and performed extensive sensitivity
analyses, including duration of vaccine protection and vaccine cost. FINDINGS:
Assuming 80% coverage and a vaccine cost per dose of $85, two-dose girls-only
vaccination (vs. no vaccination) produced cost/quality-adjusted life-year (QALY)
gained varying between $7900-24,300. The incremental cost-effectiveness ratio of
giving the third dose to girls (vs. two doses) was below $40,000/QALY-gained
when: (i) three doses provide longer protection than two doses and (ii) two-dose
protection was shorter than 30 years. Vaccinating boys (with two or three doses)
was not cost-effective (vs. girls-only vaccination) under most scenarios
investigated. INTERPRETATION: Two-dose HPV vaccination is likely to be cost
effective if its duration of protection is at least 10 years. A third dose of HPV
vaccine is unlikely to be cost-effective if two-dose duration of protection is
longer than 30 years. Finally, two-dose girls & boys HPV vaccination is unlikely
to be cost-effective unless the cost per dose for boys is substantially lower
than the cost for girls.
PMID- 25131744
TI - Primary care providers human papillomavirus vaccine recommendations for the
medically underserved: a pilot study in U.S. Federally Qualified Health Centers.
AB - INTRODUCTION: In the United States, Federally Qualified Health Centers (FQHCs)
are safety-net clinics that provide cervical cancer screening and human
papillomavirus (HPV) vaccination to medically underserved women, some of whom may
be at risk for developing cervical cancer. National guidelines recommend against
using screening test results or sexual history to determine vaccine eligibility.
Documenting HPV vaccine recommendations and beliefs of primary care providers in
FQHCs may aid in promoting evidence-based practices and prioritizing health
interventions for vulnerable populations. METHODS: Between 2009 and 2010, we
collected data from 98 primary care providers in 15 FQHC clinics in IL, USA using
a cross-sectional survey. Questions assessed provider and practice
characteristics, HPV vaccine recommendations, and provider's belief about whether
their screening and management procedures would change for women who were
vaccinated. RESULTS: 93% of providers recommended the HPV vaccine, most
frequently for females aged 13-26 years (98%). Some providers reported sometimes
to always using HPV test results (12%), Pap test results (7%), and number of
sexual partners (33%) to determine vaccine eligibility. More than half of
providers (55%) reported they will not change their screening and management
practices for vaccinated females, yet believe vaccination will yield fewer
abnormal Pap tests (71%) and referrals for colposcopy (74%). CONCLUSION: Study
providers routinely recommended the HPV vaccine for their patients. However,
providers made fewer recommendations to vaccinate females ages 9-12 years (which
includes the target age for vaccination) compared to older females, and used pre
vaccination assessments not recommended by U.S. guidelines, such as screening
test results and number of sexual partners. In order to maximize the public
health benefit of the HPV vaccine to prevent cervical cancer, adherence to
guidelines is necessary, especially in settings that provide care to medically
underserved women.
PMID- 25131745
TI - Protection of horses from West Nile virus Lineage 2 challenge following
immunization with a whole, inactivated WNV lineage 1 vaccine.
AB - Over the last years West Nile virus (WNV) lineage 2 has spread from the African
to the European continent. This study was conducted to demonstrate efficacy of an
inactivated, lineage 1-based, WNV vaccine (Equip WNV) against intrathecal
challenge of horses with a recent isolate of lineage 2 WNV. Twenty horses, sero
negative for WNV, were enrolled and were randomly allocated to one of two
treatment groups: an unvaccinated control group (T01, n=10) and a group
administered with Equip WNV (T02, n=10). Horses were vaccinated at Day 0 and 21
and were challenged at day 42 with WNV lineage 2, Nea Santa/Greece/2010.
Personnel performing clinical observations were blinded to treatment allocation.
Sixty percent of the controls had to be euthanized after challenge compared to
none of the vaccinates. A significantly lower percentage of the vaccinated
animals showed clinical disease (two different clinical observations present on
the same day) on six different days of study and the percentage of days with
clinical disease was significantly lower in the vaccinated group. A total of 80%
of the non-vaccinated horses showed viremia while only one vaccinated animal was
positive by virus isolation on a single occasion. Vaccinated animals started to
develop antibodies against WNV lineage 2 from day 14 (2 weeks after the first
vaccination) and at day 42 (the time of onset of immunity) they had all developed
a strong antibody response. Histopathology scores for all unvaccinated animals
ranged from mild to very severe in each of the tissues examined (cervical spinal
cord, medulla and pons), whereas in vaccinated horses 8 of 10 animals had no
lesions and 2 had minimal lesions in one tissue. In conclusion, Equip WNV
significantly reduced the number of viremic horses, the duration and severity of
clinical signs of disease and mortality following challenge with lineage 2 WNV.
PMID- 25131746
TI - Efficacy of live attenuated influenza vaccine against influenza illness in
children as a function of illness severity.
AB - A recent study of inactivated influenza vaccine (IIV) in children aged 3-8 years
demonstrated higher efficacy against moderate/severe influenza. A meta-analysis
of all previous published randomized clinical trials of live attenuated influenza
vaccine (LAIV) that collected information on illness severity in children aged 24
71 months was conducted. Moderate/severe influenza was defined as fever >39
degrees C, acute otitis media, or lower respiratory tract illness; other cases
were classified as milder influenza. LAIV efficacy versus placebo was 95.4% [95%
confidence interval: 88.5, 98.1] (year 1) and 88.5% [77.4, 94.9] (year 2) against
moderate/severe influenza and 91.4% [77.9, 96.7] (year 1) and 84.2% [56.7, 94.3]
(year 2) against milder influenza. The relative efficacy of LAIV versus IIV was
52.2% [31.6, 66.6] for moderate/severe influenza and 45.0% [28.6, 57.5] for
milder influenza. Efficacy against all influenza illnesses, regardless of
severity, is critical to prevent influenza illness and transmission in the
community.
PMID- 25131747
TI - Fluorescence-guided resection of high-grade gliomas: a systematic review and meta
analysis.
AB - OBJECTIVE: The present systematic review and meta-analysis was to analyze of the
advantages of intraoperative fluorescence-guided resection of high-grade gliomas.
METHODS: Systematic computerized searches of the PubMed and Web of Knowledge were
performed. The outcomes included diagnostic value for identification of tumor
tissue, gross total resection, and prognosis. The summary receiver operating
characteristic curves (SROC), the pooled sensitivities, the pooled specificities,
the pooled odd ratio (OR) and the pooled hazard ratio (HR) were estimated by meta
analysis. RESULTS: Twelve studies were included. The pooled sensitivity and the
pooled specificity for identification of tumor tissue was 0.84 (95% CI: 0.81
0.87), and 0.91 (95% CI: 0.87-0.94), respectively. And the overall weighted AUC
of the SROC curve was 0.9520 +/- 0.0116. The summary OR of the gross total
resection rate in patients with fluorescein-guided resection compared with
patients with no fluorescein was 4.372 (95% CI 2.937-6.508). Fluorescein-guided
resection was associated with a reduced risk of progression-free survival
compared with no fluorescein, with HR 0.73 (95% CI 0.57-0.94, P = 0.01). The
pooled HR of overall survival was 1.000 (95% CI 0.960-1.040) between two groups.
No significant publication bias was found. CONCLUSION: Fluorescence-guided
resection of high-grade gliomas is effective for diagnosing tumor margins,
increasing gross total resection, and reducing the risk of progression-free
survival. But this conclusion should be confirmed by large sample randomized
controlled clinical trials.
PMID- 25131749
TI - Structural effect on the resistive switching behavior of triphenylamine-based
poly(azomethine)s.
AB - Linear and hyperbranched poly(azomethine)s (PAMs)-based on triphenylamine
moieties are synthesized and used as the functioning layers in the Ta/PAM/Pt
resistive switching memory devices. Comparably, the hyperbranched PAM with
isotropic architecture and semi-crystalline nature shows enhanced memory
behaviors with more uniform distribution of the HRS and LRS resistances.
PMID- 25131748
TI - Epidemiological and evolutionary characteristics of the PRRSV in Southern China
from 2010 to 2013.
AB - In 2006, a highly pathogenic strain of porcine reproductive and respiratory
syndrome virus (HP-PRRSV) emerged in China and caused lasting damage to the swine
industry. To analyze the genetic variation of PRRSV in Southern China, 126 tissue
samples were collected; 41 ORF5 and partial Nsp2 genes were sequenced and
analyzed. The results showed that the PRRSV positive rate was 32.54% over the
last four years, that there are two main subgenotypes in Southern China, and that
the dominant strain is HP-PRRSV. An amino acid analysis of Nsp2 showed that 40
strains contained a 30-amino acid deletion in the hypervariable region. However,
the 13YJ6-8 mutant exhibited a unique amino acid deletion at positions 508-514 of
Nsp2. A phylogenetic analysis of ORF5 revealed that this mutant and five other
strains, belong to an intermediate subgenotype (inter-subgenotype), which is
characterized by extensive mutations, especially in the signal peptide and N
glycosylation sites. The results of this study demonstrate the genetic diversity
of PRRSV in Southern China and provide basic knowledge of the PRRSV epidemic in
this region.
PMID- 25131750
TI - 4-bromopropofol decreases action potential generation in spinal neurons by
inducing a glycine receptor-mediated tonic conductance.
AB - BACKGROUND AND PURPOSE: Impaired function of spinal strychnine-sensitive glycine
receptors gives rise to chronic pain states and movement disorders. Therefore,
increased activity of glycine receptors should help to treat such disorders.
Although compounds targeting glycine receptors with a high selectivity are
lacking, halogenated analogues of propofol have recently been considered as
potential candidates. Therefore we asked whether 4-bromopropofol attenuated the
excitability of spinal neurons by promoting glycine receptor-dependent
inhibition. EXPERIMENTAL APPROACH: The actions of sub-anaesthetic concentrations
of propofol and 4-bromopropofol were investigated in spinal tissue cultures
prepared from mice. Drug-induced alterations in action potential firing were
monitored by extracellular multi-unit recordings. The effects on GABAA and
glycine receptor-mediated inhibition were quantified by whole-cell voltage-clamp
recordings. KEY RESULTS: Low concentrations of 4-bromopropofol (50 nM) reduced
action potential activity of ventral horn neurons by about 30%, compared with
sham-treated slices. This effect was completely abolished by strychnine (1 MUM).
In voltage-clamped neurons, 4-bromopropofol activated glycine receptors,
generating a tonic current of 65 +/- 10 pA, while GABAA - and glycine receptor
mediated synaptic transmission remained unaffected. CONCLUSIONS AND IMPLICATIONS:
The highest glycine levels in the CNS are found in the ventral horn of the spinal
cord, a region mediating pain-induced motor reflexes and participating in the
control of muscle tone. 4-Bromopropofol may serve as a starting point for the
development of non-sedative, non-addictive, muscle relaxants and analgesics to be
used to treat low back pain.
PMID- 25131753
TI - From the Editor's perspective....
PMID- 25131752
TI - Myeloid-derived tissue-type plasminogen activator promotes macrophage motility
through FAK, Rac1, and NF-kappaB pathways.
AB - Macrophage accumulation is one of the hallmarks of progressive kidney disease.
Tissue-type plasminogen activator (tPA) is known to promote macrophage
infiltration and renal inflammation during chronic kidney injury. However, the
underlying mechanism remains largely unknown. We examined the role of tPA in
macrophage motility in vivo by tracking fluorescence-labeled bone marrow-derived
macrophages, and found that tPA-deficient mice had markedly fewer infiltrating
fluorescence-labeled macrophages than the wild-type (WT) mice. Experiments in
bone marrow chimeric mice further demonstrated that myeloid cells are the main
source of endogenous tPA that promotes macrophage migration. In vitro studies
showed that tPA promoted macrophage motility through its CD11b-mediated protease
independent function; and focal adhesion kinase (FAK), Rac-1, and NF-kappaB were
indispensable to tPA-induced macrophage migration as either infection of FAK
dominant-negative adenovirus or treatment with a Rac-1-specific inhibitor or NF
kappaB inhibitor abolished the effect of tPA. Moreover, ectopic FAK mimicked tPA
and induced macrophage motility. tPA also activated migratory signaling in vivo.
The accumulation of phospho-FAK-positive CD11b macrophages in the obstructed
kidneys from WT mice was clearly attenuated in tPA knockout mice, which also
displayed lower Rac-1 activity than their WT counterparts. Therefore, our results
indicate that myeloid-derived tPA promotes macrophage migration through a novel
signaling cascade involving FAK, Rac-1, and NF-kappaB.
PMID- 25131751
TI - Who are the children using hospice care?
AB - PURPOSE: The purpose was to examine the characteristics of children who use
hospice care. DESIGN AND METHODS: Using the Andersen Model of Health Services
Use, California Medicaid administrative databases were analyzed to describe the
characteristics of 76 children in hospice. RESULTS: The predisposing, enabling,
and need characteristics of children were identified. Children who used hospice
were a diverse group with community resources that enabled them to access care
while presenting with serious health needs. Children enrolled in hospice were
more likely older (15-20 years of age), resided nearer a pediatric hospice, and
had a serious health condition such as neuromuscular disease with multiple
comorbidities. PRACTICE IMPLICATIONS: With this knowledge, pediatric nurses can
improve their clinical practice by targeting conversations with families and
children most in need of hospice care.
PMID- 25131754
TI - Evaluation of the perception of chronic ischemic pain in humans with peripheral
arterial disease.
AB - The perception of pain is multidimensional, subjective, and unique to each
individual and can be influenced by several dimensions of pain. The objective of
this study was to evaluate the perception of chronic ischemic pain using the
descriptors of pain and to rate the main descriptors of chronic pain to people
with peripheral arterial disease (PAD). The study was conducted in two hospitals
in Brazil and consisted of two phases. In phase I, 100 participants with a
diagnosis of PAD and chronic pain evaluated 50 descriptors of pain using the
Multidimensional Pain Evaluation Scale by the psychophysical method of category
estimation using a numerical scale with 11 points. In phase II, 30 participants
judged the 10 first descriptors selected in phase I by the psychophysical method
of magnitude estimation. The average intensity of chronic ischemic pain was 5.59
+/- 3.16. The descriptors of chronic pain with higher scores obtained by the
method of category estimation were unpleasant, followed by disturbing, strong,
concern, tiring, boring, terrible, painful, sickening, and uncomfortable. By the
method of magnitude estimation, the descriptors of pain showing sensitive,
affective, and cognitive dimensions were identified by the descriptors terrible,
follow by painful, uncomfortable, concern, tiring, sickening, strong, disturbing,
boring, and unpleasant. This study showed that the chronic ischemic pain by PAD
is associated with multidimensional components of pain.
PMID- 25131756
TI - Cardiovascular risk profile of veteran men beginning androgen deprivation
therapy.
AB - We sought to describe the cardiovascular profile of veteran men before beginning
androgen deprivation therapy (ADT), with the eventual benefit of targeting
treatments to manage harmful cardiovascular side effects. We performed a
secondary analysis with chi-square and Fisher's exact tests for associations
between demographics and cardiovascular comorbidities on 375 veteran men
diagnosed with prostate cancer. Those who were overweight and current smokers
were more likely to be younger, whereas men with a systolic blood pressure >120
mmHg were more likely to be older (all P < 0.05). Men with total cholesterol 180
mg/dL were more likely to be identified in the Hispanic/other/unknown ethnicity
category. Interventions to manage cardiovascular risk should focus on preventive
lifestyle changes for younger men, and chronic disease management for older men.
Men in the smaller Hispanic/other/unknown category are at risk for
marginalization within the Veteran Administration system owing to their low
numbers and should be closely monitored for cholesterol levels when receiving
ADT.
PMID- 25131755
TI - Patient perspectives on information needs for amputation secondary to vascular
surgery: what, when, why, and how much?
AB - In patients undergoing an amputation secondary to vascular disease, little is
known about the timing, mode of delivery, or amount of information needed. The
purpose of this study was to explore the perspectives of patients who have
undergone a major lower limb amputation as a result of vascular disease,
regarding the information healthcare professionals should provide to them during
their acute hospital stay. A qualitative study using descriptive methodology was
used. Patients were included if they had a major lower limb amputation 1 week to
2 years before the interview. Purposive sampling was used. Sixteen patients
participated in a semistructured interview, either face to face or by telephone.
Interviews were transcribed verbatim. Thematic analysis was used. Transcripts
were coded by two researchers and compared. N-vivo, descriptive and
interpretative analyses were used to assess transcribed interviews. Patients
stated that there was insufficient information on a variety of topics, including
the recovery process, expectations for rehabilitation, and prosthetics. They went
on to describe that high pain levels, age, and emotional status affected the
delivery of information to them. Patients had different perspectives on timing of
information, mode of delivery, and amount of information. An individualized
approach to the delivery of information should be considered for patients
undergoing major lower limb amputation. Involved healthcare professionals need to
take into consideration patient-specific preferences and unique educational needs
before the delivery of information. We anticipate that findings from this study
will influence the development of an educational program to deliver effective
patient centered care in this unique patient population.
PMID- 25131757
TI - The predictors of surgical site infection post cardiac surgery: a systematic
review.
AB - We sought to conduct a systematic review to evaluate the predictors of surgical
site infection (SSI) after cardiac surgery. We included published, peer-reviewed,
English-language, retrospective and prospective studies identified in a search of
Medline, CINAHL, and PubMed from 2005 and through February 20, 2012. The studies
involved adults (age >18 years) undergoing cardiac surgery (defined by ICD-9
codes) and could be of any study design, in English, published within last 7
years, with data collection taking place in United States within last 10 years.
We excluded animal studies, duplicates, summaries, commentaries, editorials, case
reports, studies that conducted outside United States, and studies published
before last 7 years or studies with data collection take place before last 10
years (2002). Three types of predictors emerge: Predictors of general infection
post cardiac surgery, predictors of micro-organisms' specific SSIs and
tracheotomy, and allogenic blood transfusion as specific predictors of SSI.
Although the reviewed articles cover wide range of SSIs predictors, none of these
articles investigate preoperative skin preparation, using pre- and postoperative
prophylaxes antibiotics, postoperative wound care (appropriate time for first
dressing), and patient nutritional status as a predictors of SSIs after cardiac
surgery. Investigating these predictors for SSIs will enhance nurses'
understanding of the importance of specific types of nutrition in preventing SSIs
and enhancing wound healing, implementing a protocol for the wound care
postoperatively, and implementing a protocol for the use of prophylactic
antibiotics.
PMID- 25131758
TI - Same-day discharge after angioplasty for peripheral vascular disease: is it a
safe and feasible option?
AB - Peripheral vascular disease affects 20% of the population >55 years of age.
Patients who become symptomatic are managed by a number of technique's including
medical management, percutaneous angioplasty, bypass surgery, and in
nonreconstructable situations, limb amputation. Clinicians treating patients by
means of angioplasty have traditionally carried out these procedures on an
inpatient basis. Limited resources and pressure on the availability of inpatient
beds has necessitated clinicians to reevaluate how many of these patients are
managed. Treating suitable patients as day cases is an attractive option that
frees up resources and is financially advantageous. This paper examines the
feasibility of same-day discharge after angioplasty, with a particular emphasis
on achieving safe patient outcomes. It explores how advances in endovascular
technologies and techniques have contributed to making same-day discharge an ever
more feasible option. Nurse led pre-admission clinics run by specialist nurses
facilitate safe and appropriate patient selection, where patients at risk for
postprocedural problems can be identified effectively based on predefined
clinical criteria.
PMID- 25131759
TI - Review of article: Effectiveness of combined therapy with angiotensin-converting
enzyme inhibitors and statins in reducing mortality in diabetic patients with
critical limb ischemia: an observational study by Ezio Faglia, Giacomo Clerici,
Alessia Scatena et al (Diabetes Research and Clinical Practice 2014;103:292-297).
PMID- 25131760
TI - Review of article: Hypertension in 2014 making sense of the guidelines by
Kristine Anne Scordo, PhD, RN, ACNP-BC, FAANP, Kim Anne Pickett, MS, APRN, CDE
(Nurse Practitioner 2014;39:18-23).
PMID- 25131761
TI - Carcinogenic mechanisms of endometrial cancer: involvement of genetics and
epigenetics.
AB - Endometrial cancer is increasing worldwide and the number of patients with this
disease is likely to continue to grow, including younger patients. Many
endometrial cancers show estrogen-dependent proliferation, but the carcinogenic
mechanisms are unknown or not completely explained beyond mutations of single
oncogenes and tumor suppressor genes. Possible carcinogenic mechanisms include
imbalance between endometrial proliferation by unopposed estrogen and the
mismatch repair (MMR) system; hypermethylation of the MMR gene hMLH1; mutation of
PTEN, beta-catenin and K-ras genes in type I endometrial cancer and of HER-2/neu
and p53 genes in type II endometrial cancer; hypermethylation of SPRY2, RASSF1A,
RSK4, CHFR and CDH1; and methylation of tumor suppressor microRNAs, including miR
124, miR-126, miR-137, miR-491, miR-129-2 and miR-152. Thus, it is likely that
the carcinogenic mechanisms of endometrial cancer involve both genetic and
epigenetic changes. Mutations and methylation of MMR genes induce various
oncogenic changes that cause carcinogenesis, and both MMR mutation in germ cells
and methylation patterns may be inherited over generations and cause familial
tumorigenesis. Determination of the detailed carcinogenic mechanisms will be
useful for prevention and diagnosis of endometrial cancer, risk assessment, and
development of new treatment strategies targeting MMR genes.
PMID- 25131762
TI - Highly improved perinatal states in Japan.
AB - To report on improved perinatal states in Japan, governmental and United Nations
Children's Fund reports were analyzed. Initial maternal mortality, which was
409.8 in 1899, decreased to 4.1 in 2010, with a reduction rate of 409.8/4.1
(102.4) in 111 years: 2.5 in the initial 50 years in home delivery and 39.3 in
the later 60 years in hospital births. The difference between 2.5 versus 39.3 was
attributed to the medicine and medical care provided in hospital births. The
total reduction of neonatal mortality was 77.9/1.1 (70.8), and the rate in the
initial 50 versus later 60 years was 2.8/25. Also, there was a big difference
after introduction of extensive neonatal care. Virtual perinatal mortality after
22 weeks was estimated to be 428 in 1000 births in 1900 (i.e. those infants born
at 22-28 weeks were unlikely to survive at that time), while the perinatal
mortality was reported to be 22 weeks or more in 1979 (i.e. premature babies born
at >=22 weeks survived in 1979 because of the improved neonatal care). Actually,
60% of premature infants of 400-500 g survived in the neonatal intensive care
unit. In a recent report, 36% of infants born at 22 weeks survived to 3 years.
Although there were neurodevelopmental impairments, outcomes were improved. In
conclusion, perinatal states have remarkably improved in Japan.
PMID- 25131763
TI - Marriage and child bearing in patients with transfusion-dependent thalassemia
major.
AB - AIM: With good care, patients with transfusion-dependent thalassemia major (TDTM)
can reach older ages, marry and reproduce. This study was conducted by the
Thalassemia Research Center. MATERIAL AND METHODS: Medical notes of all TDTM
patients and all non-transfusion-dependent thalassemia major (NTDTM) patients
were reviewed from July to December 2012. Also, patients were interviewed. The
questionnaire was made in consultation with research methodology experts and
reliability was achieved by a pilot study of 12 patients, by the test-retest
method (r = 0.9). Epidemiologic characteristics of patients and the pregnancy
outcomes were recorded. Descriptive statistics were used with SPSS 17. RESULTS:
Four hundred and nineteen medical records were reviewed. Three hundred and forty
five (82.5%) were TDTM. One hundred and seventy-five (50.7%) were female with a
mean age of 25.4 +/- 7.05 years and 42 (25%) had been married. Mean age of
menarche and marriage was 15.4 +/- 1.6 and 21.8 +/- 4.5 years, respectively.
Total number of live children is nine so far. Mode of delivery in female patients
was cesarean section. Almost 78% of newborns weighed 2500-4000 g. Almost 22% of
pregnancies were assisted. Male patients consisted of 170 (49.3%) and 55 (32.3%)
of them had been married. Mean age at marriage was 24.27 +/- 3.5 years.
CONCLUSIONS: With better management, patients with TDTM can reach the age of
reproduction. Medical teams should be prepared for this possibility.
PMID- 25131764
TI - Laparoscopic cornuotomy for interstitial pregnancy and postoperative course.
AB - AIM: The aim of this study was to evaluate the advantages of laparoscopic
cornuotomy in treating interstitial pregnancy, and the effect of the procedure on
reproductive outcomes. METHODS: Thirteen patients were treated for interstitial
pregnancy by laparoscopic cornuotomy with or without local methotrexate
injection, between March 2000 and January 2012 at NTT East Japan Tohoku Hospital
and Sendai City Hospital. The patients were followed to assess the outcomes of
subsequent pregnancies for at least 1 year after the operation. RESULTS: All 13
cases of interstitial pregnancy were successfully treated by laparoscopic
cornuotomy, without performing cornual resection or laparotomy. The mean
gestational age was 7.6 +/- 1.3 weeks, and the average serum hCG level was 20,800
+/- 18,100 IU/L. The mean cornual mass size was 34.6 +/- 10.2 mm. Eight of the
patients later obtained a spontaneous intrauterine pregnancy. Three patients that
delivered by cesarean section showed no uterine dehiscence or thinning of the
scar at the site of the earlier cornual incision and repair. None of the patients
experienced uterine rupture. CONCLUSION: Interstitial pregnancy can be
selectively treated by laparoscopic cornuotomy with local methotrexate injection,
if managed carefully.
PMID- 25131766
TI - Decreased expression of elastin and lysyl oxidase family genes in urogenital
tissues of aging mice.
AB - AIM: This study aims to investigate the expression levels of elastin and lysyl
oxidase (LOX) family members in the urogenital tissues of natural aging mice and
accelerated ovarian aging mice. METHOD: Uteri, vaginas and bladders were
harvested from 18-month-old female mice and accelerated ovarian aging mice
developed by chemotherapeutic agents. Untreated 3-month-old female mice were used
as controls. The expression levels of elastin and LOX family members were
determined by real-time polymerase chain reaction and western blot. RESULTS:
Compared with untreated young female mice, the expression of elastin and LOX
family members significantly decreased both in natural aging mice and accelerated
ovarian aging mice. CONCLUSION: Aging is a high-risk factor for pelvic floor
disorders. The failure of elastic fiber synthesis and assembly due to the decline
in expression levels of elastin and LOX family members during aging may explain
the molecular mechanism causing pelvic floor disorders.
PMID- 25131765
TI - Thalidomide affects experimental endometriosis: a randomized controlled study in
the rat.
AB - AIM: This study aimed to assess the efficacy of thalidomide for treatment of
experimental endometriosis. METHODS: This study was a parallel-group, double
blind, stratified, randomized controlled animal trial with 1:1 allocation ratio.
Endometriosis was induced experimentally in 23 mature, nulligravid, female
Sprague-Dawley rats, weighing approximately 200 g and aged 2 months. A checkpoint
surgery was performed 6 weeks later. Then, the rats were randomly allocated into
the thalidomide (22 mg/day p.o.) and control (0.5 mL saline 0.9%/day p.o.) groups
of nine. After 6 weeks, they were killed. Before each laparotomy, blood for
leukocyte and lymphocyte counts and during them, implants for histopathology and
peritoneal fluid for interleukin (IL)-6, tumor necrosis factor-alpha and vascular
endothelial growth factor (VEGF)-A concentrations (by enzyme-linked immunoassay)
were collected. Allocation and stratified randomization were done using a
computer, based on the obtained histopathology scores of the implants of the
checkpoint surgery. RESULTS: The histopathology scores (the main outcome measure)
were 2.00 +/- 1.55 versus 0.44 +/- 1.01 (P = 0.035). The comparisons of after
treatment counts of leukocytes, lymphocytes, VEGF-A and IL-6 between the two
groups were statistically significant. CONCLUSION: The results of this study are
in favor of therapeutic implication of thalidomide in experimental endometriosis
in rats. This is the first time thalidomide has been evaluated on endometriosis
in an animal model.
PMID- 25131767
TI - Successful ex utero intrapartum treatment procedure for prenatally diagnosed
severe micrognathia: a case report.
AB - We present a case of fetal severe micrognathia in which successful airway
stabilization was achieved by an ex utero intrapartum treatment procedure. In
this case, it was anticipated that the infant would have a vulnerable airway at
birth based on in utero sonographic findings, including an extremely hypoplastic
jaw, worsening polyhydramnios and absence of stomach visualization. Early
sonographic recognition was helpful in preparing the parents and physicians for
the possibility of airway emergencies during the perinatal period. When a
severely hypoplastic mandible accompanied by polyhydramnios and absent stomach
visualization is noted on ultrasound, clinicians should consider the indication
for ex utero intrapartum treatment. A multidisciplinary team with technically
skilled medical providers should be coordinated to perform the procedure.
PMID- 25131768
TI - Case of concurrent benign metastasizing leiomyoma in the lung and
retroperitoneum, with a focus on its etiology.
AB - We report a rare, simultaneous occurrence of benign metastasizing leiomyoma in
the lung and retroperitoneum in a 49-year-old woman who had previously undergone
myomectomy at 35 years of age and hysterectomy at 45 years of age for multiple
recurrences of histologically benign uterine leiomyomas. At 49 years of age,
computed tomography-guided biopsy indicated benign metastasizing leiomyomas in
the lung. In addition, a retroperitoneal leiomyoma was found that was resected
along with both the ovaries via laparotomy. No sign or symptom of recurrence was
observed 5 years later. The coexistence of benign metastasizing leiomyoma in the
lung and retroperitoneum following surgery for conventional leiomyomas has rarely
been reported. Further, the nature and etiology of benign metastasizing leiomyoma
are still not well understood. This case is therefore worth reporting, and
exploring its etiology is important.
PMID- 25131769
TI - Patient-reported outcome measures in pediatric epilepsy: a content analysis using
World Health Organization definitions.
AB - OBJECTIVE: Patient-reported outcome (PRO) measures that assess the effect of
epilepsy on children's lives include the concepts of health, health-related
quality of life (HRQOL), and quality of life (QOL). They also contain varied
health and health-related content. Our objectives were to identify what generic
and epilepsy-specific PRO instruments are used in childhood epilepsy research and
to make explicit their conceptual approach and biopsychosocial content. METHODS:
MEDLINE, EMBASE, and PsycINFO were searched from 2001 to 2011 for PRO measures
used in pediatric epilepsy. Measures were analyzed on an item-by-item basis
according to World Health Organization (WHO) definitions of QOL and the
International Classification of Functioning, Disability and Health for Children
and Youth (ICF-CY) biopsychosocial health framework to distinguish the conceptual
approach within each measure. The health content analysis coded each item
according to specific ICF-CY components of body function, activity and
participation, environment, or personal factors to determine the health content
for each measure. RESULTS: Three generic and 13 epilepsy-specific PRO measures
were identified; 10 of 16 measures utilized a biopsychosocial health approach
rather than an HRQOL or QOL approach. Content analysis showed that in 11 of 16
measures, >25% of the items represented participation and activity components of
the ICF-CY, whereas a high proportion of environment items were found in only one
epilepsy-specific measure. SIGNIFICANCE: This comprehensive review provides
information aiding clinicians and researchers in the selection of the appropriate
PRO instruments for children with epilepsy on the basis of content. Most epilepsy
specific and generic PROs use a biopsychosocial health approach as opposed to a
subjective HRQOL/QOL approach to measurement. Clinicians and researchers must be
aware of these concepts and content when intending to measure outcomes validly.
PMID- 25131770
TI - SIRT1 regulates oncogenesis via a mutant p53-dependent pathway in hepatocellular
carcinoma.
AB - BACKGROUND & AIMS: SIRT1 is a class III histone deacetylase that plays diverse
roles in various cancers. However, the clinical significance of SIRT1 in
hepatocellular carcinoma (HCC) remains unknown. METHODS: We analysed p53
mutations and the activation of SIRT1 in 252 hepatitis B virus-positive HCC
cases. None of the patients had been subjected to pre-operative treatment.
RESULTS: We examined 57 p53 mutations from 248 HCC tissues. Activated SIRT1
(phosphorylated form of Ser47), in the context of mutant p53, predicted a longer
relapse-free survival (RFS) but not a longer overall survival (OS) (RFS: p =
0.007, OS: p = 0.280) in HCC tissues harbouring mutant p53. In multivariate
analysis, activated SIRT1 remained a significant predictor of longer RFS (OR =
0.307, CI: 0.143-0.660, p=0.002). Analysis of 248 paired specimens revealed a
significant correlation between activated SIRT1 (Ser47) and activated AMPK
(Thr172) in HCC tissues harbouring mutant p53 (p = 0.003, n = 57). The
combination of these 2 parameters was a powerful predictor for a good prognosis
in these patients. In vitro, SIRT1 inactivation stimulated the growth of HCC
cells, bearing mutated p53, by suppressing AMPK activity and subsequently
enhancing mammalian target of rapamycin (mTOR) activity, resulting in induction
of p70S6K1 activation in HCC cells. Metformin, an AMPK activator, more strongly
suppressed cell growth in p53-mutant cell lines with inactive SIRT1 than in p53
mutant cell lines with active SIRT1. CONCLUSIONS: SIRT1 exerted anti-carcinogenic
effects via the AMPK-mTOR pathway in HCC in the context of mutant p53. Metformin
could be a therapeutic drug for HCC in patients with mutated p53, inactivated
SIRT1, and AMPK expression.
PMID- 25131771
TI - A heterogeneous hierarchy of co-regulatory receptors regulates exhaustion of HCV
specific CD8 T cells in patients with chronic hepatitis C.
AB - BACKGROUND & AIMS: The functionality of virus-specific T cells is regulated by a
sophisticated network of an expanding repertoire of co-regulatory receptors,
which could be harnessed for immunotherapeutic applications. However, targeting
particular pathways during persistent virus infections has resulted in variable
outcomes. The extent to which T cell exhaustion can be reversed, by targeting
multiple co-regulatory pathways, still remains not fully investigated. METHODS:
We analysed the phenotype and in vitro functionality of HCV-specific CD8(+) T
cells expressing PD-1, CTLA-4, TIM-3 or 2B4 either alone or in various
combinations and compared expression levels to those of cytomegalovirus (CMV) and
Epstein-Barr virus (EBV) specific T cells in peripheral blood mononuclear cells
(PBMCs) from the same cohort of patients with chronic hepatitis C (CHC)
infection. RESULTS: Blockade and/or crosslinking of distinct co-regulatory
pathways in exhausted HCV-specific CD8(+) T cells resulted in rather diverse and
individualized T cell responses, irrespective of the type and number of receptors
targeted. Overall, in vitro manipulations of these pathways yielded three
response possibilities: (i) total non-response (ii) good single blockade response
and (iii) good dual/multiple blockade response, with each comprising
approximately one-third of the patients tested. The diversity of the in vitro
responsiveness of HCV-specific T cells was reflected by an enormous ex vivo
phenotypic heterogeneity. Despite this broad heterogeneity, HCV-specific CD8(+) T
cells differed from EBV- and CMV-specific T cells in particular by TIM-3
expression, which also correlated with liver disease activity and viral load.
CONCLUSIONS: HCV-specific CD8(+) T cell functionality, upon co-regulatory
receptor manipulations, was characterized by an individual pattern of responses
in patients with CHC, suggesting that treatment approaches, targeting these
receptors, should consider inter-individual differences and be personalized.
PMID- 25131772
TI - Regulatory T cells and autoimmune hepatitis: what happens in the liver stays in
the liver.
PMID- 25131773
TI - Effects of atorvastatin on bone mineral density (BMD) and bone metabolism in
elderly males with osteopenia and mild dyslipidemia: a 1-year randomized trial.
AB - We explored the effects of atorvastatin on BMD and biochemical markers of bone
metabolism in a 1-year, prospective, randomized controlled study. 64 male
patients with osteopenia and mild dyslipidemia (mean age 80.1+/-6.6 years) were
randomized to a 1-year atorvastatin treatment or control. BMD of hip and lumbar
spine was measured with dual-energy X-ray absorptionmetry (DXA). Bone metabolic
markers including resorption markers beta-c-terminal telopeptide of type I
collagen (CTx), formative markers osteocalcin (OC), 25-hydroxyvitamin D (25(OH)D)
were measured with electrochemiluminescence immunoassay (ECLIA). Other bone
metabolism markers including intact parathyroid hormone (iPTH) and testosterone
were measured with chemiluminescence enzyme immunoassay (CLEIA). Levels of serum
lipid and biochemical parameters were measured with automatic biochemical
analyzer. All the parameters were recorded at baseline, and at 6 and 12 months,
respectively. Compared with the control group, the atorvastatin treatment group
showed significant reduction of triglyceride (TG, P<0.01) and low-density
lipoprotein cholesterol (LDL-C, P<0.01). At 12 month, total hip BMD in
atorvastatin group was significantly higher (P<0.01) compared with the control
group, while there were no similar effect on femoral neck or lumbar spine between
the two groups (P=0.48 and 0.53 respectively). Meanwhile, CTx significantly
reduced in atorvastatin treatment group (P<0.001) compared with baseline. Our
findings suggest that in elderly male patients with osteopenia and mild
dyslipidemia, therapeutic doses of atorvastatin were associated with positive
effects on BMD, probably mediated by suppressed bone resorption.
PMID- 25131774
TI - Efficacy of an anticoccidial live vaccine in prevention of necrotic enteritis in
chickens.
AB - Necrotic enteritis (NE) is an important disease in poultry caused by Clostridium
perfringens combined with predisposing factors, mainly eimeriosis. In the present
study, we investigated the protective effect of a commercial attenuated
anticoccidial live vaccine against NE in a clinical infection model using 60 day
old chicks. Vaccination was performed on study day (SD) 1 with natural booster
infections for 4 weeks from Eimeria spp. oocysts present in litter. On SD 28,
five groups were formed (n=12): group V+/C-E- (vaccinated, uninfected), group
V+/C-E+ (vaccinated, infected with Eimeria spp.), group V+/C+E+ (vaccinated,
infected with clostridia and Eimeria spp.), group V-/C+E+ (unvaccinated, infected
with clostridia and Eimeria spp.), and group NC (negative control). Efficacy was
measured by clinical parameters, pathogen multiplication, and pathological
parameters assessed during two necropsies on SD 34 and SD 40, respectively.
Additionally, cytokine expression was measured in gut and spleen tissues at
necropsy. Clinical signs of NE were observed only in the coinfected groups,
mainly in group V-/C+E+. Accordingly, lowest body weight gain was observed in
group V-/C+E+ (301.8 g from SD 28 to SD 40; group NC: 626.2 g). Oocyst excretion
varied significantly (P<0.01) between all Eimeria spp. infected groups and was
highest in group V-/C+E+, followed by V+/C+E+, and lowest in group V+/C-E+. NE
typical intestinal lesions showed only in groups V+/C+E+ and V-/C+E+. The
intestinal mucosa featured partly severe lesions in the jejunum, C. perfringens
colonization was histologically visible. Upregulation of IFN-gamma, was observed
in the jejunal tissue of group V-/C+E+ (P<0.01 (SD 34) or P<0.05 (SD 40) compared
to all other groups). IL-10 and IL-12 were upregulated in group V-/C+E+, IL-10
also in group V+/C+E+ (SD 40) while IL-2 expression remained unaltered. In
conclusion, vaccination against coccidiosis was effective in preventing NE in a
mixed infection comparable to field situations.
PMID- 25131775
TI - Insights into the olfactory system of the ectoparasite Caligus rogercresseyi:
molecular characterization and gene transcription analysis of novel ionotropic
receptors.
AB - Although various elements of the olfactory system have been elucidated in
insects, it remains practically unstudied in crustaceans at a molecular level.
Among crustaceans, some species are classified as ectoparasites that impact the
finfish aquaculture industry. Thus, there is an urgent need to identify and
comprehend the signaling pathways used by these in host recognition. The present
study, through RNA-seq and qPCR analyses, found novel transcripts involved in the
olfactory system of Caligus rogercresseyi, in addition to the transcriptomic
patterns expressed during different stages of salmon lice development. From a
transcriptomic library generated by Illumina sequencing, contigs that annotated
for ionotropic receptors and other genes implicated in the olfactory system were
identified and extracted. Full length mRNA was obtained for the ionotropic
glutamate receptor 25, which had 3923 bp, and for the glutamate receptor
ionotropic kainate 2, which had 2737 bp. Furthermore, two other transcripts
identified as glutamate receptor, ionotropic kainate 2-like were found. In silico
analysis was performed for the transcription expression from different stages of
development in C. rogercresseyi, and clusters according to RPKM values were
constructed. Gene transcription data were validated through qPCR assays in
ionotropic receptors, and showed an expression of glutamate receptor 25
associated with the copepodid stage whereas adults, especially male adults, were
associated with the kainate 2 and kainate 2-like transcripts. Additionally, gene
transcription analysis of the ionotropic receptors showed an overexpression in
response to the presence of masking compounds and immunostimulant in salmon
diets. This response correlated to a reduction in sea lice infection following in
vivo challenge. Diets with masking compounds showed a decrease of lice
infestation of up to 25%. This work contributes to the available knowledge on
chemosensory systems in this ectoparasite, providing novel elements towards
understanding the host-finding process of the salmon louse C. rogercresseyi.
PMID- 25131776
TI - Rhodnius prolixus: modulation of antioxidant defenses by Trypanosoma rangeli.
AB - Trypanosoma rangeli is a protozoan parasite of insects and mammals that is
challenged by the constant action of reactive oxygen species, generated either by
its own metabolism or through the host immune response. The aim of this work was
to investigate whether T. rangeli is able to modify the redox state of its insect
vector, Rhodnius prolixus, through the modulation of such antioxidant enzymes as
superoxide dismutase (SOD), catalase, and GPx present in the midgut of the
insect. We verified that in R. prolixus fed with blood infected with T. rangeli
there is an increase in SOD activity in the anterior and posterior midguts.
However, the activities of enzymes related to hydrogen peroxide and
hydroperoxides metabolism, such as catalase and GPx, were decreased in relation
to the insect control group, which was only fed blood. These changes in the redox
state of the vector led to an increase in lipid peroxidation and thiol oxidation
levels in the anterior and posterior midgut tissues. We also verified that the
addition of 1 mM GSH in the blood meal of the infected insects increased the
proliferation of these parasites by 50%. These results suggest that there is an
increase in oxidative stress in the insect gut during T. rangeli infection, and
this condition could contribute to the control of the proliferation of these
parasites.
PMID- 25131777
TI - One minute ultraviolet exposure inhibits Toxoplasma gondii tachyzoite replication
and cyst conversion without diminishing host humoral-mediated immune response.
AB - We developed a protocol to inactivate Toxoplasma gondii (T. gondii) tachyzoites
employing 1 min of ultraviolet (UV) exposure. We show that this treatment
completely inhibited parasite replication and cyst formation in vitro and in vivo
but did not affect the induction of a robust IgG response in mice. We propose
that our protocol can be used to study the contribution of the humoral immune
response to rodent behavioral alterations following T. gondii infection.
PMID- 25131779
TI - Breast health in developing countries.
AB - Breast cancer is one of the leading cancers world-wide. While the incidence in
developing countries is lower than in developed countries, the mortality is much
higher. Of the estimated 1 600 000 new cases of breast cancer globally in 2012,
794 000 were in the more developed world compared to 883 000 in the less
developed world; however, there were 198 000 deaths in the more developed world
compared to 324 000 in the less developed world (data from Globocan 2012, IARC).
Survival from breast cancer depends on two main factors--early detection and
optimal treatment. In developing countries, women present with late stages of
disease. The barriers to early detection are physical, such as geographical
isolation, financial as well as psychosocial, including lack of education, belief
in traditional medicine and lack of autonomous decision-making in the male
dominated societies that prevail in the developing world. There are virtually no
population-based breast cancer screening programs in developing countries.
However, before any screening program can be implemented, there must be
facilities to treat the cancers that are detected. Inadequate access to optimal
treatment of breast cancer remains a problem. Lack of specialist manpower,
facilities and anticancer drugs contribute to the suboptimal care that a woman
with breast cancer in a low-income country receives. International groups such as
the Breast Health Global Initiative were set up to develop economically feasible,
clinical practice guidelines for breast cancer management to improve breast
health outcomes in countries with limited resources.
PMID- 25131780
TI - Perineuronal net, CSPG receptor and their regulation of neural plasticity.
AB - Perineuronal nets (PNNs) are reticular structures resulting from the aggregation
of extracellular matrix (ECM) molecules around the cell body and proximal neurite
of specific population of neurons in the central nervous system (CNS). Since the
first description of PNNs by Camillo Golgi in 1883, the molecular composition,
developmental formation and potential functions of these specialized
extracellular matrix structures have only been intensively studied over the last
few decades. The main components of PNNs are hyaluronan (HA), chondroitin sulfate
proteoglycans (CSPGs) of the lectican family, link proteins and tenascin-R. PNNs
appear late in neural development, inversely correlating with the level of neural
plasticity. PNNs have long been hypothesized to play a role in stabilizing the
extracellular milieu, which secures the characteristic features of enveloped
neurons and protects them from the influence of malicious agents. Aberrant PNN
signaling can lead to CNS dysfunctions like epilepsy, stroke and Alzheimer's
disease. On the other hand, PNNs create a barrier which constrains the neural
plasticity and counteracts the regeneration after nerve injury. Digestion of PNNs
with chondroitinase ABC accelerates functional recovery from the spinal cord
injury and restores activity-dependent mechanisms for modifying neuronal
connections in the adult animals, indicating that PNN is an important regulator
of neural plasticity. Here, we review recent progress in the studies on the
formation of PNNs during early development and the identification of CSPG
receptor - an essential molecular component of PNN signaling, along with a
discussion on their unique regulatory roles in neural plasticity.
PMID- 25131778
TI - Tissue inhibitor of metalloproteinases (TIMP)-1 creates a premetastatic niche in
the liver through SDF-1/CXCR4-dependent neutrophil recruitment in mice.
AB - Due to its ability to inhibit prometastatic matrix metalloproteinases, tissue
inhibitor of metalloproteinases (TIMP)-1 has been thought to suppress tumor
metastasis. However, elevated systemic levels of TIMP-1 correlate with poor
prognosis in cancer patients, suggesting a metastasis-stimulating role of TIMP-1.
In colorectal cancer patients, tumor as well as plasma TIMP-1 levels were
correlated with synchronous liver metastasis or distant metastasis-associated
disease relapse. In mice, high systemic TIMP-1 levels increased the liver
susceptibility towards metastasis by triggering the formation of a premetastatic
niche. This promoted hepatic metastasis independent of origin or intrinsic
metastatic potential of tumor cells. High systemic TIMP-1 led to increased
hepatic SDF-1 levels, which in turn promoted recruitment of neutrophils to the
liver. Both inhibition of SDF-1-mediated neutrophil recruitment and systemic
depletion of neutrophils reduced TIMP-1-induced increased liver susceptibility
towards metastasis. This indicates a crucial functional role of neutrophils in
the TIMP-1-induced premetastatic niche. CONCLUSION: Our results identify TIMP-1
as an essential promoter of hepatic premetastatic niche formation.
PMID- 25131781
TI - [Bicarbonate reabsorption in proximal renal tubule: molecular mechanisms and
metabolic acidosis].
AB - HCO3(-) reabsorption in the renal tubules plays a critically important role in
maintaining the global acid-base balance. Loss of HCO3(-) causes metabolic
acidosis. Proximal renal tubule is the major site for HCO3(-) reabsorption,
accounting for more than 80% of total HCO3(-) reabsorption along the nephron.
Over the past more than half centuries, tremendous progresses have been made on
understanding the molecular mechanisms underlying the HCO3(-) reabsorption in
proximal tubules. The transepithelial movement of HCO3(-) involves the
coordinated operation of machineries on both the apical and the basolateral
membranes of the epithelial cells. On the apical domain, Na(+)-H(+) exchanger
NHE3 and the vacuolar H(+)-ATPase are two major pathways mediating the apical
uptake of HCO3(-)-related species. Taken together, NHE3 and H(+)-ATPase are
responsible for about 80% of HCO3(-) reabsorption in the proximal tubule. The
remaining 20% is likely mediated by pathways yet to be characterized. On the
basolateral membrane, NBCe1 represents the only major known pathway mediating the
extrusion of HCO3(-) coupled with Na(+) into the interstitial space. In the
present article, we provide a historical view about the studies on the mechanisms
of HCO3(-) reabsorption since 1940s. Moreover, we summarize the latest progresses
emerging over the past decade in the physiological as well as pathological roles
of acid-base transporters underlying the HCO3(-) reabsorption in proximal
tubules.
PMID- 25131782
TI - [Progress on Hedgehog signaling transduction].
AB - Hedgehog (Hh) signaling pathway plays an important role during embryonic
development and pattern formation. Disruption of Hh pathway results in various
developmental disorders and increasing cancer incidence. Here we provide a
comprehensive review of the pathway members, focusing on how mammalian Hh
regulates the Gli family of transcription factors through its downstream members,
the so-called "canonical signaling pathway". Hh signaling pathway is highly
conserved among species, and primary cilia plays an important role as a
"signaling center" during vertebrate signal transduction. Further, in the past
few years, numerous studies have shown that Hh signal can also be transduced
through Gli-independent ways collectively referred to as "non-canonical signaling
pathways", which can be subdivided into two modules: (i) those not requiring Smo
and (ii) those downstream of Smo that do not require Gli transcription factors.
Thus, we review the rapid progress on canonical and non-canonical Hh pathways.
PMID- 25131783
TI - [HCN ion channel: biological characteristics and functions in pain].
AB - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in vertebrate
are reverse voltage-dependent, and its activation depends on the
hyperpolarization of cell and may be directly or indirectly regulated by the
cyclic adenosine monophosphate (cAMP) or other signal transduction cascades. The
distribution, quantity, and activation states of HCN channels differ in tissues
throughout the body. By modulating If/If current, HCN channels may influence the
resting membrane potential, and thus importantly regulate neuronal excitability,
dendritic integration of synaptic potentials, and synaptic transmission. Evidence
exhibits that HCN channels participate in pain and other physiological and
pathological process. Pharmacological treatment targeting HCN channels is of
benefit to relieve pain and other related diseases.
PMID- 25131784
TI - [Upregulation of P2X3 receptors in dorsal root ganglion of TRPV1 knockout female
mice].
AB - The study was aimed to investigate the changes in mechanical pain threshold in
the condition of chronic inflammatory pain after transient receptor potential
vanilloid 1 (TRPV1) gene was knockout. Hind-paw intraplantar injection of
complete freund's adjuvant (CFA, 20 MUL) produced peripheral inflammation in wild
type and TRPV1 knockout female mice. The mechanical pain thresholds were measured
during the 8 days after injection and pre-injection by using Von-Frey hair. Nine
days after injection, mice were killed and the differences of expression of c-Fos
and P2X3 receptor in the dorsal root ganglia (DRG) and spinal cord dorsal horn
were examined by Western blotting between the two groups. Compared with that in
wild-type mice, the mechanical pain threshold was increased significantly in
TRPV1 knockout mice (P < 0.05); 3 days after CFA injection, the baseline
mechanical pain threshold in the TRPV1 knockout mice group was significantly
higher than that in the wild-type mice group (P < 0.05); The result of Western
blotting showed that the expression of c-Fos protein both in DRG and spinal cord
dorsal horn of TRPV1 knockout mice group was decreased significantly compared
with that in wild-type mice group (P < 0.01, P < 0.05), while the expression of
P2X3 receptor in DRG of TRPV1 knockout mice group was increased significantly
compared with that in wild-type mice group (P < 0.05). Our findings indicate that
TRPV1 may influence the peripheral mechanical pain threshold by mediating the
expression of c-Fos protein both in DRG and spinal cord dorsal horn and changing
the expression of P2X3 receptor in DRG.
PMID- 25131785
TI - [Effect of pulse magnetic field on distribution of neuronal action potential].
AB - The biological effect on the organism generated by magnetic field is widely
studied. The present study was aimed to observe the change of sodium channel
under magnetic field in neurons. Cortical neurons of Kunming mice were isolated,
subjected to 15 Hz, 1 mT pulse magnetic stimulation, and then the currents of
neurons were recorded by whole-cell patch clamp. The results showed that, under
magnetic stimulation, the activation process of Na(+) channel was delayed, and
the inactivation process was accelerated. Given the classic three-layer model,
the polarization diagram of cell membrane potential distribution under pulse
magnetic field was simulated, and it was found that the membrane potential
induced was associated with the frequency and intensity of magnetic field. Also
the effect of magnetic field-induced current on action potential was simulated by
Hodgkin-Huxley (H-H) model. The result showed that the generation of action
potential was delayed, and frequency and the amplitudes were decreased when
working current was between -1.32 MUA and 0 MUA. When the working current was
higher than 0 MUA, the generation frequency of action potential was increased,
and the change of amplitudes was not obvious, and when the working current was
lower than -1.32 MUA, the time of rising edge and amplitudes of action potential
were decreased drastically, and the action potential was unable to generate.
These results suggest that the magnetic field simulation can affect the
distribution frequency and amplitude of action potential of neuron via sodium
channel mediation.
PMID- 25131786
TI - [MrgC receptor activation reverses chronic morphine-evoked alterations of
glutamate transporters and nNOS in rats].
AB - This study was aimed to investigate the mechanisms underlying the modulation
effect of Mas-related gene (Mrg) C receptors (MrgC) on morphine tolerance.
Saline, morphine (20 MUg), morphine plus bovine adrenal medulla 8-22 (BAM8-22, 1
nmol) or (Tyr(6))-2-MSH-6-12 (MSH, 5 nmol) were administered intrathecally in
rats for 6 days. Pain-related molecules in the spinal cord and dorsal root
ganglion (DRG) were examined using Western blot, immunocytochemistry and RT-PCR
techniques. The results showed that intrathecal administration of the selective
MrgC receptor agonists (BAM8-22 or MSH) remarkably attenuated or abolished
chronic morphine-evoked reduction in glutamate transporters (GLAST, GLT-1 and
EAAC1) in the spinal cord and increase in neuronal nitric oxide synthase (nNOS)
in the spinal cord as well as DRG. In addition, MrgC receptor-like
immunoreactivity (IR) was detected in superficial laminae of the spinal cord.
Chronic morphine induced significant increases in MrgC receptor-IR in the spinal
cord and MrgC receptor mRNA levels in DRG. These results suggest that the
modulation of pro-nociceptive mediators in the spinal cord and DRG underlies the
inhibition of morphine tolerance by MrgC receptor activation.
PMID- 25131787
TI - [Characteristic research of Uyghur and Chinese semantic cognition in event
related potentials].
AB - The present study investigated the characteristic of semantic cognition of Uyghur
Chinese bilinguals. The event-related potentials (ERP) technique was used to
explore the characteristic of N400 wave and topographic map of difference-waves
with "picture-word" semantic priming paradigm. There were significant semantic
priming effects on two languages. The average amplitude of N400 was similar in
two languages, while average amplitudes of three electrodes (F3, F4, PZ) in
Chinese were negative than others. Meanwhile, the activation of topographic map
of Uyghur was almost in all regions except occipital lobe, and the degree of
activation of Chinese was less than Uyghur, but the activation in parietal and
bilateral frontal lobes was higher. In conclusion, the present study suggests
that two languages of Uyghur-Chinese bilinguals are all sensitive to semantic
priming. The bilateral frontal and parietal lobes participate in language
switching. Semantic cognition of two languages in Uyghur-Chinese late non
proficient bilinguals is both completed by bilateral cerebral hemispheres. We
have not found obvious lateralization on two languages of Uyghur-Chinese
bilinguals.
PMID- 25131788
TI - [Activation of TNF-alpha and signaling pathway in the hypothalamus of the rats
subjected to chronic unpredictable mild stressors after middle cerebral artery
occlusion].
AB - This study was aimed to investigate the changes of the hypothalamic-pituitary
adrenal axis (HPAA) activity and the cytokines system in the hypothalamus of the
depressive rats which were exposed to chronic unpredictable mild stressors (CUMS)
after middle cerebral artery occlusion (MCAO). By means of qRT-PCR, ELISA and
Western blot, mRNA and/or protein expressions of corticotropin releasing factor
(CRF), tumor necrosis factors-alpha (TNF-alpha), suppressor of cytokines
signaling 3 (SOCS3), phosphorylation of signal transducers and activators of
transcription 3 (pSTAT3) were measured in the hypothalamus of rats. The results
showed that, compared with control group, CUMS+MCAO group exhibited increased
mRNA levels of CRF, TNF-alpha, SOCS3, as well as up-regulated CRF, TNF-alpha,
SOCS3 and pSTAT3 protein expressions. Furthermore, there were correlations
between CRF and TNF-alpha, TNF-alpha and SOCS3, SOCS3 and pSTAT3, respectively.
These observations indicated the CRF system was activated in the post stroke
depression (PSD) status. The TNF-alpha and its signaling pathway, STAT3/SOCS3,
were up-regulated in mRNA and protein levels. In conclusion, this study presents
the evidence which supports the hypothesis of signaling cross-talk between the
CRF system and TNF-alpha signaling pathway after ischemic stroke and CUMS.
PMID- 25131789
TI - [Effect of high-mobility group box 1 on the proliferation of primary neural stem
cells in vitro].
AB - The cell counting kit-8 (CCK-8) proliferation assay and diameter measure of
neurospheres were used to investigate the effect of high-mobility group box 1
(HMGB1) on proliferation of primary rat neural stem cells (NSCs) in vitro, and c
Jun N-terminal protein kinase (JNK) potent inhibitor SP600125 was used to study
the mechanism. The results demonstrated that HMGB1 significantly increased CCK-8
absorbance values and neurosphere diameters at concentrations of 1 and 10 ng/mL
at 48 h and 72 h (P < 0.05), and the other HMGB1 concentration groups (0.01, 0.1,
100 ng/mL) showed no significant difference, compared with control group (P >
0.05). HMGB1 at 10 ng/mL significantly increased the NSCs proliferation
accompanied by the rising of phosphorylated JNK levels (P < 0.01), and 10 MUmol/L
SP600125 prevented these effects in HMGB1-cultured NSCs (P < 0.01). In
conclusion, low concentration of HMGB1 (1-10 ng/mL) can increase NSCs
proliferation, which may play a role by promoting JNK phosphorylation.
PMID- 25131790
TI - [2-Bromoethylamine protects vascular endothelium by inhibiting SSAO activity in
diabetic rats].
AB - The purpose of this study was to investigate the change of aortic semicarbazide
sensitive amine oxidase (SSAO) activity in diabetic rats and examine the effect
of 2-bromoethylamine (2-BEA) on SSAO activity and vascular endothelium in
diabetic rats. SSAO was prepared from rat aorta. For assessment of the inhibitory
effect, the enzymes were preincubated in the presence of different concentrations
of 2-BEA before the addition of benzylamine in vitro. Type 1 diabetic rat model
was induced by a single intraperitoneal injection of streptozotocin (STZ).
Sprague Dawley (SD) rats were randomly divided into normal control group (NC),
diabetic model group (DM), 2-BEA 5 mg/kg group, 2-BEA 20 mg/kg group (n = 10 in
each group). 2-BEA was administered daily via intraperitoneal injection for 8
weeks. At the end of 8 weeks, blood sample was collected from the abdominal
aorta. Plasma nitric oxide (NO) was determined by nitrate reductase method.
Plasma endothelin-1 (ET-1) was determined by radioimmunoassay. Aorta SSAO was
determined by high performance liquid chromatography. The aorta was prepared to
observe morphological changes and ultramicroscopic structures. The results were
as follows: Compared with NC group, aortic SSAO activity and the plasma ET-1 were
significantly increased (P < 0.01), and plasma NO was significantly decreased (P
< 0.01) in DM group. 2-BEA decreased plasma ET-1 and elevated plasma NO by
inhibiting aortic SSAO activity in diabetic rats (P < 0.01), and 2-BEA 20 mg/kg
group was more significant than 2-BEA 5 mg/kg group (P < 0.05). Endothelial
injury of 2-BEA group rats was less serious than DM group. These results suggest
that 2-BEA protect aortic endothelium by inhibiting aortic SSAO activity.
PMID- 25131791
TI - [Abnormal calcium re-uptake in myocardium sarcoplasmic reticulum in rabbits with
heart failure and the influencing factors].
AB - The aim of the present study was to investigate the abnormal calcium re-uptake
function of myocardium sarcoplasmic reticulum (SR) in rabbits with heart failure,
as well as potential mechanisms. Heart failure model was established in rabbits
through aortic insufficiency and constriction of abdominal aorta. The SR Ca(2+)
re-uptake function was measured with a calcium imaging device. The activity of
myocardium SR calcium adenodine triphosphatase 2a (SERCA2a) was measured by
inorganic phosphate. The protein expressions of SERCA2a, CaMKII, PKA, PP1alpha,
phospholamban (PLB), PLB-Ser(16) and PLB-Thr(17) were evaluated by Western blot.
The activities of PKA and CaMKII were detected by gamma-(32)P substrate
incorporation. The results showed that, compared with the sham operation group,
the heart failure group exhibited reduced Ca(2+) re-uptake amount (P < 0.01) and
the expression and activity of SERCA2a (P < 0.05 or P < 0.01), decreased
expression of PLB and its phosphorylation status in sites of Ser(16) and Thr(17)
(P < 0.05), increased expressions and activities of PKA and CaMKII (P < 0.05 or P
< 0.01), and increased expression of PP1alpha (P < 0.05). These results suggest
that the abnormal Ca(2+) re-uptake function in heart failure is related with
reduced expression and activities of SERCA2a, as well as reduced expression of
PLB and its phosphorylation status. Both PLB-Ser(16) and -Thr(17) may be involved
in the regulation of myocardium SR calcium pump activity in heart failure.
PMID- 25131792
TI - [Ox-LDL down-regulates expression of pigment epithelium-derived factor in human
umbilical vein endothelial cells].
AB - Pigment epithelium-derived factor (PEDF) is a multifunctional protein with anti
inflammatory, antioxidant and antithrombotic properties and plays a protective
role against atherosclerosis (AS). The purpose of the present study is to explore
the effects of oxidized low density lipoprotein (ox-LDL) on the expression of
PEDF in cultured human umbilical vein endothelial cells (HUVECs). HUVECs were
cultured and incubated with ox-LDL at different concentrations (6.25, 12.5, 25,
50, 100 and 150 mg/L) for 24 h. Apoptosis of endothelial cells were assayed by
morphological staining and flow cytometry. The intracellular reactive oxygen
species (ROS) levels were measured by flow cytometry. Cell viability was assayed
by MTT assay. PEDF protein and mRNA expressions in HUVECs were analyzed by
Western blot and quantitative real-time PCR, respectively. The results showed
that ox-LDL significantly induced apoptosis, reduced cell viability, increased
intracellular ROS levels and decreased the PEDF expression in HUVECs in a
concentration-dependent manner. Ox-LDL at 50 mg/L obviously decreased the PEDF
protein expression compared with control group (P < 0.05), whereas 25 mg/L ox-LDL
already markedly reduced the PEDF mRNA expression (P < 0.05). In conclusion, the
results suggest that ox-LDL down-regulates the PEDF expression through an
increased ox-LDL-induced intracellular production of ROS.
PMID- 25131793
TI - Sequencing approaches in cancer treatment.
AB - Use of sequencing approaches is an important aspect in the field of cancer
genomics, where next-generation sequencing has already been utilized for
targeting oncogenes or tumour-suppressor genes, that can be sequenced in a short
time period. Alterations such as point mutations, insertions/deletions, copy
number alterations, chromosomal rearrangements and epigenetic changes are
encountered in cancer cell genomes, and application of various NGS technologies
in cancer research will encounter such modifications. Rapid advancement in
technology has led to exponential growth in the field of genomic analysis. The
$1000 Genome Project (in which the goal is to sequence an entire human genome for
$1000), and deep sequencing techniques (which have greater accuracy and provide a
more complete analysis of the genome), are examples of rapid advancements in the
field of cancer genomics. In this mini review, we explore sequencing techniques,
correlating their importance in cancer therapy and treatment.
PMID- 25131794
TI - Costs and outcome of assertive community treatment (ACT) in a rural area in
Denmark: 4-year register-based follow-up.
AB - PURPOSE: Health economic evidence of assertive community treatment (ACT) in
Denmark is limited. The aim of the study was to assess the costs and outcome of
ACT among 174 patients with severe and persistent mental illness in a rural area
of Denmark. METHODS: The study was based on a quasi-experimental design with a
control group from the neighbouring region. Costs and retention in mental health
services were analysed by using register data 1 year before and 4 years after
inclusion in the study. Data on the use of supportive housing were available for
the year before baseline and the subsequent 2 years only. RESULTS: Seventy eight
percent of the patients receiving ACT were in contact with psychiatric services
at the 4-year follow-up, while 69% of the patients in the control group had
contact with psychiatric services (P < 0.17). Days in supportive housing were
lower for the ACT group before baseline and remained so (dropping to zero) for
the subsequent 2 years. Over 4 years, the mean total costs per patient in the
group receiving ACT were DDK 493,442 (SE = 34,292). Excluding costs of supportive
housing, the mean total costs per patient of the control group were DDK 537,218
(SE = 59,371), P < 0.53. If these costs are included, however, the mean total
costs for the ACT group are unchanged, whereas costs for the control group rise
to DDK 671,500 (SE = 73,671), P < 0.03. CONCLUSION: While ACT appears to have
resulted in a significant reduction in costs for psychiatric hospitalizations,
baseline differences in use of supportive housing make the effects of ACT on
overall costs more ambiguous. At worst, however, overall costs did not increase.
Given the generally acknowledged clinical benefits of ACT over standard
outpatient care, the results support further dissemination of ACT in Denmark.
PMID- 25131795
TI - Electronic monitoring of psychomotor activity as a supplementary objective
measure of depression severity.
AB - BACKGROUND: Rating scales used to assess the severity of depression e.g. the
Hamilton Depression Rating Scale 17-item (HDRS-17) partly rely on the patient's
subjective experience and reporting. Such subjective measures tend to have low
reliability and adding objective measures to complement the assessment of
depression severity would be a major step forward. AIMS: To investigate
correlations between electronic monitoring of psychomotor activity and severity
of depression according to HDRS-17. METHODS: A total of 36 patients with unipolar
disorder (n = 18) or bipolar disorder (n = 18) and 31 healthy control persons
aged 18-60 years were included. Psychomotor activity was measured using a
combined heart rate and movement sensor device (Actiheart) for 3 consecutive
days, 24 h a day. RESULTS: We found that sleeping heart rate (beats/min)
correlated with HDRS-17 in both patients with unipolar disorder and bipolar
disorder (unadjusted model: B = 0.46, 95% CI 0.037-0.89, P = 0.034). In contrast,
correlations between activity energy expenditure (kJ/kg/day), cardio-respiratory
fitness (mlO2/min/kg) and HDRS-17 were non-significant. CONCLUSIONS: These
results suggest that measuring sleeping heart rate in non-experimental daily life
could be an objective supplementary method to measure the severity of depression
and perhaps indicate presence of insomnia.
PMID- 25131796
TI - Stability and changes in metabolically healthy overweight or obesity and risk of
future diabetes: Niigata wellness study.
AB - OBJECTIVE: Stability and changes in obesity and metabolic health status from a
baseline period and longitudinally investigated their impact on predicting future
diabetes were assessed. METHODS: Studied were 27,478 Japanese individuals without
diabetes. Metabolically healthy (MH) was indicated by having <=1 among impaired
fasting glucose, hypertension, hypertriglyceridemia and low HDL cholesterol
concentration. Metabolically abnormal (MA) was indicated by having >=2 of those
metabolic abnormalities. A cut-off value of BMI 25.0 defined overweight or
obesity (O) or normal weight (NW). Hazard ratio (HR) for diabetes for a 6-year
period was investigated after changes in phenotypes were assessed during the
previous 2 years. RESULTS: Compared with maintaining MH-NW, transitioning to MH-O
from MH-NW resulted in a multivariate-adjusted HR of 1.96 (95% CI: 1.18, 3.25)
for diabetes. With a stable MH-O the HR for diabetes was 2.59 (2.00, 3.34) while
change from MH-O to MH-NW resulted in an HR of 1.30 (0.61, 2.76). Transitioning
to MA-O from MH-O was associated with an HR of 7.09 (5.41, 9.30). With a stable
MA-O the risk of diabetes was substantially elevated with an HR of 12.5 (10.5,
14.9). CONCLUSIONS: Examining the transitory nature of apparently benign or
unhealthy obese phenotypes was effective for differentiating high-risk
individuals for future diabetes.
PMID- 25131798
TI - Disparate postoperative results in the first and second knees on simultaneous
bilateral total knee arthroplasty.
AB - We hypothesized that the circumstances of the two consecutive operations of a
simultaneous bilateral total knee arthroplasty (TKA) are different, and could
lead to different outcomes of overlapping bilateral TKAs. Both knees of 420
subjects were evaluated in the current study. In the second TKA, there were more
incidence rates of outlier in mechanical femoro-tibial angle (16.2% vs. 9.0%),
more blood loss (735 vs. 656 mL), and longer operation time (61, 58 minutes
respectively), as compared to the first TKA, while no significant differences in
clinical outcomes. In conclusion, there were no significant differences in the
clinical outcomes even though few distinct outcomes due to different
circumstances of the surgery. Awareness of these findings can help the continued
success of bilateral TKA in an increasing patient population.
PMID- 25131799
TI - Enhancing the performance of accelerated MRI through preservation of acquisition
SNR: An "aliased" k-space approach.
AB - PURPOSE: A method for preserving acquisition SNR through simultaneous
acquisitions of distinct k-space phase encodes to enhance the performance of
accelerated MRI is presented. THEORY AND METHODS: An excitation module comprising
RF pulses and gradients is inserted into a sequence of choice to overlap and
acquire distinct k-space phase encodes. This accelerates a scan as all phase
encodes can now be acquired in a duration shorter than that of a typical scan.
Next, this "aliased k-space" is restored during reconstruction using receiver
sensitivity profiles. When the aliased k-space is also sub-sampled for additional
acceleration, Parallel Imaging (PMRI) is applied first to synthesize the
unacquired aliased samples. The synthesized samples are then used with the
acquired samples in an iterative reconstruction to obtain the output. RESULTS:
Depending on the sequence, acquisition SNR increased by 18-25% relative to PMRI
or by 5% relative to the unaccelerated scan. This compensates for the SNR loss
when the aliased k-space is sub-sampled for additional acceleration. With PMRI,
the method could enable acceleration factors as high as 12 in 2D cartesian scans.
CONCLUSION: A method for accelerating MRI scans through aliased k-space
acquisitions and the feasibility of combining the same with PMRI for greater
acceleration has been demonstrated. Magn Reson Med 74:150-161, 2015. (c) 2014
Wiley Periodicals, Inc.
PMID- 25131797
TI - p21/Cyclin E pathway modulates anticlastogenic function of Bmi-1 in cancer cells.
AB - Apart from regulating stem cell self-renewal, embryonic development and
proliferation, Bmi-1 has been recently reported to be critical in the maintenance
of genome integrity. In searching for novel mechanisms underlying the
anticlastogenic function of Bmi-1, we observed, for the first time, that Bmi-1
positively regulates p21 expression. We extended the finding that Bmi-1
deficiency induced chromosome breaks in multiple cancer cell models.
Interestingly, we further demonstrated that knockdown of cyclin E or ectopic
overexpression of p21 rescued Bmi-1 deficiency-induced chromosome breaks. We
therefore conclude that p21/cyclin E pathway is crucial in modulating the
anticlastogenic function of Bmi-1. As it is well established that the
overexpression of cyclin E potently induces genome instability and p21 suppresses
the function of cyclin E, the novel and important implication from our findings
is that Bmi-1 plays an important role in limiting genomic instability in cylin E
overexpressing cancer cells by positive regulation of p21.
PMID- 25131800
TI - Phenolic compounds in grains, sprouts and wheatgrass of hulled and non-hulled
wheat species.
AB - BACKGROUND: The use of sprouts and young plantlets in human nutrition is
increasing because they often contain phytochemicals and other high value
nutrients. This is also the case for wheat, although there is no literature for
hulled wheat species. Thus we determined total polyphenols, phenolic acids (PAs),
fibre and minerals in grains, 5-day-old sprouts and 12-day-old wheatgrass of
einkorn (cv. Monlis), emmer (cvs Augeo, Rosso Rubino, Zefiro), spelt (cvs Pietro,
Giuseppe), durum wheat (cv. Creso) and soft wheat (cv. Orso). RESULTS: Grains of
einkorn and emmer contained twice bound PAs as compared to soft and durum wheat
and spelt, with p-coumaric acid accounting for about 50% of total bound PAs. In
wheatgrass, differences between species for bound PAs decreased due to a decrease
in einkorn and emmer and an increase in soft and durum wheat. In all species,
total phenols and free PAs increased passing from grains to sprouts and
wheatgrass. Neutral and acid detergent fibre content increased with sprouting
only in einkorn and emmer. CONCLUSION: Our evidence suggests that the grains of
einkorn and emmer and the sprouts and wheatgrass of all Triticum species might
potentially be valuable for the development of functional foods.
PMID- 25131801
TI - CD4 trajectory adjusting for dropout among HIV-positive patients receiving
combination antiretroviral therapy in an East African HIV care centre.
AB - OBJECTIVE: Estimates of CD4 response to antiretroviral therapy (ART) obtained by
averaging data from patients in care, overestimate population CD4 response and
treatment program effectiveness because they do not consider data from patients
who are deceased or not in care. We use mathematical methods to assess and adjust
for this bias based on patient characteristics. DESIGN: We examined data from
25,261 HIV-positive patients from the East Africa IeDEA Consortium. METHODS: We
used inverse probability of censoring weighting (IPCW) to represent patients not
in care by patients in care with similar characteristics. We address two
questions: What would the median CD4 be "had everyone starting ART remained on
observation?" and "were everyone starting ART maintained on treatment?" RESULTS:
Routine CD4 count estimates were higher than adjusted estimates even under the
best-case scenario of maintaining all patients on treatment. Two years after
starting ART, differences between estimates diverged from 30 cells/uL, assuming
similar mortality and treatment access among dropouts as patients in care, to
over 100 cells/uL assuming 20% lower survival and 50% lower treatment access
among dropouts. When considering only patients in care, the proportion of
patients with CD4 above 350 cells/uL was 50% adjusted to below 30% when
accounting for patients not in care. One-year mortality diverged 6-14% from the
naive estimates depending on assumptions about access to care among lost
patients. CONCLUSIONS: Ignoring mortality and loss to care results in over
estimation of ART response for patients starting treatment and exaggerates the
efficacy of treatment programs administering it.
PMID- 25131803
TI - The health perspectives of Australian adolescents from same-sex parent families:
a mixed methods study.
AB - BACKGROUND: Research involving adolescents from same-sex parent families provides
an important contribution to the evidence base on their health, well-being and
the impact of stigma. To date reports on the perspectives of adolescents with
same-sex attracted parents have been limited. This study aimed to describe the
multidimensional experiences of physical, mental and social well-being of
adolescents living in this context. METHODS: A mixed methods study of adolescents
with same-sex attracted parents comprising of an adolescent-report survey of 10-
to 17-year-olds and family interviews with adolescents and their parents. Data
were collected in 2012 and 2013 as part of the Australian Study of Child Health
in Same-Sex Families. RESULTS: The findings from qualitative interviews with
seven adolescents and responses to an open-ended survey question (n = 16) suggest
four themes: perceptions of normality, positive concepts of health, spheres of
life (including family, friends and community) and avoiding negativity. The
quantitative sample of adolescents with same-sex attracted parents (n = 35)
reported higher scores than population normative data on the dimensions general
health and family activities within the Child Health Questionnaire (CHQ) as well
as higher on the peer problems scale on the Strengths and Difficulties
Questionnaire (SDQ). Perceived stigma correlates with lower health and well-being
overall. CONCLUSIONS: Positive health outcomes are informed by the ways
adolescents conceptualize health and how they construct their spheres of life.
Peer relationships, and community perspectives of same-sex families, inform
perceived stigma and its correlation with poorer health and well-being. Although
adolescents see their families as essentially normal they are negatively affected
by external societal stigma.
PMID- 25131802
TI - Initial solid tumor testing (stage 1) of AZD1480, an inhibitor of Janus kinases 1
and 2 by the pediatric preclinical testing program.
AB - BACKGROUND: AZD1480 is an ATP competitive inhibitor of Janus kinases 1 and 2
(JAK1, 2) that has been shown to inhibit the growth of solid tumor models. This
agent was selected for testing the putative role of JAK/STAT signaling in the
standard PPTP solid tumor models. PROCEDURES: AZD1480 was tested against the PPTP
in vitro cell line panel at concentrations from 1.0 nM to 10 MUM and against the
PPTP in vivo solid tumor xenograft panels at (60 mg/kg once daily (SID) * 5) for
three consecutive weeks. Additional studies evaluated 5 to 20 mg/kg BID * 5 with
SID dosing at 7-30 mg/kg at weekends for three consecutive weeks. RESULTS: In
vitro the median relative IC50 (rIC50 ) for the PPTP cell lines was 1.5 uM, with
a range from 0.3 uM to 5.9 uM. The two cell lines with rIC50 values of 0.3 uM
both had ALK activating genomic alterations. AZD1480 demonstrated statistically
significant differences (P < 0.05) in EFS distribution compared to control in 89%
of the solid tumor xenografts. AZD1480 induced intermediate (EFS T/C > 2) or high
level growth inhibition in 15 of 30 (50%) solid tumor xenografts. Tumor
regressions were observed in three of six Wilms tumor models at doses that
induced inhibition of Stat3(Y705) phosphorylation. CONCLUSIONS: AZD1480
demonstrated significant tumor growth inhibition against most PPTP solid tumor
xenografts, similar to that observed for antiangiogenic agents tested by the
PPTP. Tumor regressing activity was noted for Wilms tumor xenografts.
PMID- 25131804
TI - Hydranencephaly in a newborn with a FLVCR2 mutation and prenatal exposure to
cocaine.
AB - BACKGROUND: Hydranencephaly is a relatively rare but severe structural brain
abnormality that often results in perinatal death. Although several factors
including infection and multiple births have been reported to be associated with
this birth defect, the underlying etiology is not well understood. Recently,
FLVCR2 gene mutations have been implicated in a subset of hydranencephaly cases,
following an autosomal recessive pattern of inheritance. CASE: We report a male
infant with hydranencephaly found to have a previously unreported six amino acid
deletion in one copy of the FLVCR2 gene following a pregnancy complicated by poor
prenatal care and maternal cocaine use. Although our patient currently presents
with developmental delays, he is showing progress and gaining some skills.
CONCLUSION: We discuss the possibility of a synergistic effect between the FLVCR2
genetic mutation and environmental cocaine exposure, creating a susceptible
brain, as an explanation for this infant's phenotype. This case demonstrates the
potential clinical utility of testing for mutations in FLVCR2 for patients with
hydranencephaly after other possible etiologies, such as congenital infection,
have been reasonably eliminated. Current literature on FLVCR2 is relatively
sparse; identifying additional patients with similar mutations will aid in
defining the clinical significance of a gene mutation and the contribution to the
etiology of hydranencephaly.
PMID- 25131805
TI - Hepatic fungal infection in a young beagle with unrecognised hereditary cobalamin
deficiency (Imerslund-Grasbeck syndrome).
AB - A 12-month-old beagle presented for anorexia, pyrexia and vomiting. The dog had
been treated intermittently with antibiotics and corticosteroids for inappetence
and lethargy since five months of age. Previous laboratory abnormalities included
macrocytosis and neutropenia. At presentation, the dog was lethargic, febrile and
thin. Laboratory examination findings included anaemia, a left shift,
thrombocytopenia, hypoglycaemia and hyperbilirubinaemia. Multiple, small,
hypoechoic, round hepatic lesions were observed on abdominal ultrasound.
Cytological examination of hepatic fine needle aspirates revealed a fungal
infection and associated pyogranulomatous inflammation. The dog's general
condition deteriorated despite supportive measures and treatment with
fluconazole, and owners opted for euthanasia before hypocobalaminaemia was
identified. Subsequent genomic analysis revealed a CUBN:c.786delC mutation in a
homozygous state, confirming hereditary cobalamin malabsorption (Imerslund
Grasbeck syndrome). Similar to human infants, dogs with Imerslund-Grasbeck
syndrome may rarely be presented for infectious diseases, distracting focus from
the underlying primary disorder.
PMID- 25131808
TI - Discovery of natural infection by Metagonimus hakubaensis Shimazu, 1999
(Trematoda: Heterophyidae) in Japanese water shrews (Chimarrogale platycephala)
in Japan.
AB - A total of 611 preserved adult Metagonimus spp. specimens recovered from 32 of 53
Japanese water shrews (Chimarrogale platycephala) that had previously been
collected in Aomori Prefecture between June 1994 and August 1996, were examined
in this study. Morphological examination revealed that 603 of these flukes were
identical to M. hakubaensis Shimazu, 1999, and that the others were M. takahashii
Suzuki, 1930 (n=4), M. otsurui Saito et Shimizu, 1968 (n=2), and M. miyatai Saito
et al., 1997 (n=2). Each of the 32 Japanese water shrews infected with M.
hakubaensis contained between 1 and 83 flukes. This is the first record of the
natural final host for M. hakubaensis, since this fluke species was described.
PMID- 25131807
TI - G-CSF: From granulopoietic stimulant to bone marrow stem cell mobilizing agent.
AB - G-CSF was among the first cytokines to be identified and rapidly transitioned
into clinical medicine. Initially used to promote the production of neutrophils
in patients with chemotherapy-induced neutropenia it helped to revolutionize the
delivery of cancer therapy. Its ability to mobilize hematopoietic stem cells from
the bone marrow into the blood was subsequently exploited, changing the face of
hematopoietic stem cell transplantation. Today the knowledge gained in unraveling
the mechanisms of stem cell mobilization by G-CSF is being explored as a means to
increase chemosensitivity in hematological malignancies. This review provides a
brief history of G-CSF and then focuses on recent advances in our understanding
of G-CSF-induced stem cell mobilization and the potential clinical application of
this knowledge in chemo-sensitization.
PMID- 25131806
TI - Personality assessment inventory internalizing and externalizing structure in
veterans with posttraumatic stress disorder: associations with aggression.
AB - Posttraumatic stress disorder (PTSD) is associated with aggressive behavior in
veterans, and difficulty controlling aggressive urges has been identified as a
primary postdeployment readjustment concern. Yet only a fraction of veterans with
PTSD commit violent acts. The goals of this study were to (1) examine the higher
order factor structure of Personality Assessment Inventory (PAI) scales in a
sample of U.S. military veterans seeking treatment for PTSD; and (2) to evaluate
the incremental validity of higher-order latent factors of the PAI over PTSD
symptom severity in modeling aggression. The study sample included male U.S.
Vietnam (n = 433) and Iraq/Afghanistan (n = 165) veterans who were seeking
treatment for PTSD at an outpatient Veterans Affairs (VA) clinic. Measures
included the Clinician Administered PTSD Scale, the PAI, and the Conflict Tactics
Scale. The sample was randomly split into two equal subsamples (n's = 299) to
allow for cross-validation of statistically derived factors. Parallel analysis,
variable clustering analysis, and confirmatory factor analyses were used to
evaluate the factor structure, and regression was used to examine the association
of factor scores with self-reports of aggression over the past year. Three
factors were identified: internalizing, externalizing, and substance abuse.
Externalizing explained unique variance in aggression beyond PTSD symptom
severity and demographic factors, while internalizing and substance abuse did
not. Service era was unrelated to reports of aggression. The constructs of
internalizing versus externalizing dimensions of PTSD may have utility in
identifying characteristics of combat veterans in the greatest need of treatment
to help manage aggressive urges.
PMID- 25131809
TI - Phylogenetic analysis of fowl adenoviruses isolated from chickens with gizzard
erosion in Japan.
AB - Thirty-four fowl adenoviruses (FAdVs) isolated from chickens with gizzard erosion
(GE) from 1999 to 2010 were characterized phylogenetically together with foreign
isolates. The phylogenetic analysis based on part of the hexon gene classified
these 34 FAdV isolates into 3 groups: FAdV-1, -8a and 8b, thereby suggesting that
FAdVs associated with GEs in chickens are diverse. All 30 FAdV-1 isolates were
genetically identical, and they were also identical with FAdV-1 isolates from GEs
in chickens in European countries (Germany, Poland, Austria, Hungary and Italy).
Thus, the same type of FAdV-1 has been associated with outbreaks of GE in
Japanese chickens for the past 10 years, which may have spread from a common
ancestor, although the epidemiological relationship is unknown.
PMID- 25131810
TI - Overexpression of EZH2 associates with a poor prognosis in chronic lymphocytic
leukemia.
AB - EZH2, a histone methyltransferase, is overexpressed in several human tumors, but
whether it exerts any impact in chronic lymphocytic leukemia (CLL) remains
unknown. We used real time PCR to investigate the expression profile of EZH1 and
EZH2 in 59 CLL patients, 10 samples of purified B-cells from healthy donors and
12 normal adult tissues. EZH2 was overexpressed in CLL patients and correlates
with high white blood cell count, ZAP-70 expression and chromosomal
abnormalities. EHZ1 expression does not correlate with CLL progression. EZH2
overexpression is related to a poor prognosis of CLL and could be a useful tool
to assess its aggressiveness.
PMID- 25131812
TI - Strategies addressing barriers to clinical trial enrollment of underrepresented
populations: a systematic review.
AB - BACKGROUND: Underrepresentation of racial and ethnic minorities in clinical
trials remains a reality while they have disproportionately higher rates of
health disparities. OBJECTIVE: The purpose of this study was to identify
successful community-engaged interventions that included health care providers as
a key strategy in addressing barriers to clinical trial enrollment of
underrepresented patients. DESIGN: A systematic review of the literature on
interventions addressing enrollment barriers to clinical trials for racial and
ethnic minorities was performed in Ovid MEDLINE, EBSCO Megafile, and EBSCO
CINAHL. The systematic review identified 360 studies, and 20 were selected using
the inclusion criteria. An iterative process extracted information from the
eligible studies. RESULTS: The 20 selected studies were analyzed and then grouped
by first author, nature of the clinical research initiative, priority
populations, key strategies, and study outcomes. Nine of the studies addressed
cancer clinical trials and 11 related to chronic medical conditions, including
diabetes, hypertension management, and chronic kidney disease. The key strategies
employed were categorized according to their presumed impact on barriers incurred
at distinct steps in study recruitment: clinical trial awareness, opportunity to
participate, and acceptance of enrollment. The strategies were further
categorized by whether they would address barriers associated with minority
perceptions of the research process and barriers related to how studies were
designed and implemented. CONCLUSION: Multiple and flexible strategies targeting
providers and participants at provider sites and within communities might be
needed to enroll underrepresented populations into clinical trials.
PMID- 25131813
TI - ClereMed: Lessons Learned From a Pilot Study of a Mobile Screening Tool to
Identify and Support Adults Who Have Difficulty With Medication Labels.
AB - BACKGROUND: In order to take medications safely and effectively, individuals need
to be able to see, read, and understand the medication labels. However, one-half
of medication labels are currently misunderstood, often because of low literacy,
low vision, and cognitive impairment. We sought to design a mobile tool termed
ClereMed that could rapidly screen for adults who have difficulty reading or
understanding their medication labels. OBJECTIVE: The aim of this study was to
build the ClereMed prototype; to determine the usability of the prototype with
adults 55 and over; to assess its accuracy for identifying adults with low
functional reading ability, poor ability on a real-life pill-sorting task, and
low cognition; and to assess the acceptability of a touchscreen device with older
adults with age-related changes to vision and cognition. METHODS: This pilot
study enrolled adults (>=55 years) who were recruited through pharmacies,
retirement residences, and a low-vision optometry clinic. ClereMed is a hypertext
markup language (HTML)-5 prototype app that simulates medication taking using an
iPad, and also provides information on how to improve the accessibility of
prescription labels. A paper-based questionnaire included questions on
participant demographics, computer literacy, and the Systems Usability Scale
(SUS). Cognition was assessed using the Montreal Cognitive Assessment tool, and
functional reading ability was measured using the MNRead Acuity Chart. Simulation
results were compared with a real-life, medication-taking exercise using
prescription vials, tablets, and pillboxes. RESULTS: The 47 participants had a
mean age of 76 (SD 11) years and 60% (28/47) were female. Of the participants,
32% (15/47) did not own a computer or touchscreen device. The mean SUS score was
76/100. ClereMed correctly identified 72% (5/7) of participants with functional
reading difficulty, and 63% (5/8) who failed a real-life pill-sorting task, but
only 21% (6/28) of participants with cognitive impairment. Participants who owned
a computer or touchscreen completed ClereMed in a mean time of 26 (SD 16)
seconds, compared with 52 (SD 34) seconds for those who do not own a device
(P<.001). Those who had difficulty, struggled with screen glare, button
activation, and the "drag and drop" function. CONCLUSIONS: ClereMed was well
accepted by older participants, but it was only moderately accurate for reading
ability and not for mild cognitive impairment. Future versions may be most useful
as part of a larger medication assessment or as a tool to help family members and
caregivers identify individuals with impaired functional reading ability. Future
research is needed to improve the sensitivity for measuring cognitive impairment
and on the feasibility of implementing a mobile app into pharmacy workflow.
PMID- 25131814
TI - In memoriam: Geoffrey Louis Zubay, 1931-2014. Pioneer in cell-free gene
expression studies and molecular genetics.
PMID- 25131815
TI - Holliday junction processing enzymes as guardians of genome stability.
AB - Holliday junctions (HJs) are four-stranded DNA intermediates that arise during
the recombinational repair of DNA double-strand breaks (DSBs). Their timely
removal is crucial for faithful chromosome segregation and genome stability. In
mammalian cells, HJs are processed by the BTR (BLM-topoisomerase IIIalpha-RMI1
RMI2) complex, the SLX-MUS (SLX1-SLX4-MUS81-EME1) complex, and the GEN1
resolvase. Recent studies have linked the deficiency of one or more of these
enzymes to perturbed DNA replication, impaired crosslink repair, chromosomal
instability, and defective mitoses, coupled with the transmission of widespread
DNA damage and high levels of mortality. We review these key advances and how
they have cemented the status of HJ-processing enzymes as guardians of genome
integrity and viability in mammalian cells.
PMID- 25131811
TI - Grip it and rip it: structural mechanisms of DNA helicase substrate binding and
unwinding.
AB - Maintenance and faithful transmission of genomic information depends on the
efficient execution of numerous DNA replication, recombination, and repair
pathways. Many of the enzymes that catalyze steps within these pathways require
access to sequence information that is buried in the interior of the DNA double
helix, which makes DNA unwinding an essential cellular reaction. The unwinding
process is mediated by specialized molecular motors called DNA helicases that
couple the chemical energy derived from nucleoside triphosphate hydrolysis to the
otherwise non-spontaneous unwinding reaction. An impressive number of high
resolution helicase structures are now available that, together with equally
important mechanistic studies, have begun to define the features that allow this
class of enzymes to function as molecular motors. In this review, we explore the
structural features within DNA helicases that are used to bind and unwind DNA. We
focus in particular on "aromatic-rich loops" that allow some helicases to couple
single-stranded DNA binding to ATP hydrolysis and "wedge/pin" elements that
provide mechanical tools for DNA strand separation when connected to
translocating motor domains.
PMID- 25131816
TI - Import routes and nuclear functions of Argonaute and other small RNA-silencing
proteins.
AB - Small RNAs are important regulators of gene expression in many different
organisms. Nuclear and cytoplasmic biogenesis enzymes generate functional small
RNAs from double-stranded (ds) or single-stranded (ss) RNA precursors, and mature
small RNAs are loaded into Argonaute proteins. In the cytoplasm, small RNAs guide
Argonaute proteins to complementary RNAs leading to cleavage of these targets,
translational silencing, or mRNA decay. In the nucleus Argonaute proteins engage
in transcriptional silencing processes such as epigenetic silencing of repetitive
elements at the chromatin level. During the past few years many novel functions
of small RNA-guided gene silencing proteins in the nucleus have been reported.
However, their specific import routes are largely unknown. In this review we
summarize the current knowledge on nuclear transport routes that Argonaute and
other RNA-silencing proteins take to carry out their various functions in the
nucleus.
PMID- 25131818
TI - An unusual case of preexcitation treated with a pacemaker.
PMID- 25131817
TI - Prognostic value of cyclooxygenase-2 gene polymorphisms in advanced non-small
cell lung cancer patients treated with first-line platinum-based chemotherapy.
AB - AIM: Cyclooxygenase-2 (COX-2) plays an important role in cell apoptosis,
angiogenesis and tumor invasion, and over-expression of COX-2 is associated with
tumor development and occurrence. The aim of this study is to investigate the
association between COX-2 polymorphisms and clinical outcomes in advanced non
small cell lung cancer (NSCLC) patients treated with first-line platinum-based
chemotherapy. METHODS: A total of 190 patients with IIIB or IV NSCLC who received
platinum-based chemotherapy were recruited in this study. Four functional COX-2
polymorphisms, including rs689465, rs689466, rs3218625 and rs20417, were
genotyped by PCR-based restriction fragment length polymorphism methods. Kaplan
Meier methods were used to compare survival by different genotypes. Cox
proportional hazard models were used to identify independently significant
variables. RESULTS: The rs689465 AA genotype was significantly associated with
longer overall survival (OS) (13.0 months vs 8.8 months, P = 0.019 for log-rank
test; hazard ratio [HR] 0.624; 95% confidence internal [CI] 0.418-0.931) and
progression-free survival (5.3 months vs 4.0 months, P = 0.018 for log-rank test;
HR 0.627; 95% CI 0.421-0.934) compared with AG or GG genotype, especially in
patients with adenocarcinoma (P = 0.002), performance status of 1 (P = 0.009) and
stage IV disease (P = 0.012), and treated with gemcitabine-based chemotherapy (P
= 0.012). Multivariate regression analysis showed that COX-2 rs689465
polymorphism had a significantly independent prognostic value for OS (P = 0.017,
HR = 1.637, 95% CI = 1.093-2.453). CONCLUSION: Our study suggested that rs689465
polymorphism could be a prognostic biomarker for advanced NSCLC patients treated
with first-line platinum-based chemotherapy.
PMID- 25131819
TI - Heart failure in adult congenital heart disease.
AB - OPINION STATEMENT: Adult congenital heart disease (ACHD) patients represent a
special population in modern cardiology: though their numbers are growing, and
they represent a high-resource utilization subgroup, a robust evidence-base of
randomized trials is lacking. Much of the standard therapy is adapted from the
treatment of ischemic and idiopathic left ventricle systolic failure, with a
small, but growing body of evidence on medical therapy in select ACHD diagnoses.
At our institution, for instance, there is a long tradition of using angiotensin
antagonists in patients with a systemic right ventricle to prevent deleterious
remodeling. The effects of beta-blockers on functional class in ACHD are yet
unproven, but there is promising data on pulmonary vasodilators. Control of
coronary risk factors and aerobic exercise should be considered for all.
Prevention of arrhythmias is important, and multi-site pacing is an emerging
therapy. New prognostic tools including natriuretic peptides and CPET are
increasingly used to guide earlier initiation of these therapies.
PMID- 25131820
TI - Perioperative physiology and pharmacology in the obese small animal patient.
AB - OBJECTIVE: To review the available literature concerning the physiologic and
pharmacologic alterations induced by obesity in canine and feline patients and
their relevance to perioperative care. STUDY DESIGN: Literature review.
DATABASES: PubMed, CAB, Web of Science. CONCLUSIONS: Obesity of cats and dogs is
a chronic inflammatory condition that is increasingly prevalent. Similar to the
situation in humans, small animal obesity may be associated with changes in
endocrine, respiratory, and cardiovascular function. In addition, alteration of
body composition in obesity can affect pharmacokinetic variables. Modifications
in perioperative care may need to be made for obese dogs and cats, including
attention to respiratory and cardiovascular supportive care and drug dose
adjustments.
PMID- 25131821
TI - Microscopic and ultrastructural features in Wolcott-Rallison syndrome, a
permanent neonatal diabetes mellitus: about two autopsy cases.
AB - BACKGROUND: Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive
disorder characterized by the association of permanent neonatal or early-infancy
insulin-dependent diabetes, multiple bone dysplasia, hepatic dysfunction, and
growth retardation. All clinical manifestations result from gene mutations
encoding pancreatic endoplasmic reticulum eIF2 alpha kinase (PERK), an
endoplasmic reticulum transmembrane protein that plays a role in the unfolded
protein response. Histological and ultrastructural lesions of bone and pancreas
have been described in animal models and WRS patients. However, histological and
ultrastructural findings of other organs, especially of the liver, are lacking.
METHODS: Autopsy specimens from two pediatric patients with WRS were analyzed. An
immunohistochemical study was performed on the pancreas. An ultrastructural study
was realized from samples of liver, pancreas, kidney, and myocardium. Our
findings were compared with those of the literature and correlated with the
molecular data. RESULTS: Hepatocytes and pancreatic exocrine cells exhibited very
peculiar features of necrosis suggestive of secondary changes because of
endoplasmic reticulum overload. Steatosis occurred in renal tubular cells,
hepatocytes, and myocardial fibers. Abnormal mitochondria were noted in renal and
myocardial fibers. Pancreas islets were characterized by a marked reduction in
the number of insulin-secreting beta cells. CONCLUSIONS: The histological and
ultrastructural features that occur in WRS are directly or indirectly linked to
endoplasmic reticulum (ER) dysfunction and can explain the peculiar phenotype of
this syndrome.
PMID- 25131822
TI - Serological characterization of occult hepatitis B virus infection among blood
donors in India.
AB - INTRODUCTION: Discovery of hepatitis B infections characterized by the presence
of viral genome without detectable HBsAg (Occult Hepatitis; OBI) has initiated a
considerable amount of research in this regard. Our study is a serological and
molecular characterization of OBI among the donors who donated at our blood bank
during the study period. MATERIAL AND METHOD: During the study period HBsAg ELISA
non reactive ID-NAT reactive donors samples were screened for presence of
antibody against HBc, HBs and HBe. Molecular analysis of these NAT yield samples
was undertaken for detection of the viral load and genotyping. RESULT: We studied
28,134 HBsAg ELISA non reactive donor samples. On testing them with ID-NAT, HBV
DNA was detected in 25 samples. Eighteen samples out of these 25 NAT yield were
further worked up. The 66.6% of the NAT yield samples (12 out of 18) were
reactive for antibody against HBc. The 25% (3 out of 12) of these NAT yield
samples having antibody against core antigen also had antibody against HBs. The
27.7% (5 out of 18) of NAT yield detected by ID-NAT did not have any detectable
serological marker in blood. Four out of 12 core antibody positive NAT yield
samples had genotype A HBV infection. CONCLUSION: As per our study molecular
detection of HBV DNA by ID-NAT, we were able to analyze 18 HBV NAT yield cases
among 28,134 HBsAg ELISA non reactive donors. Out of 18, 12 donors were OBI
whereas the rest (6) were in window period (WP yield) of HBV infection. One out
of every 3.6 NAT yield detected by ID-NAT was non reactive for all serological
markers.
PMID- 25131823
TI - Diffusion tensor tractography in hypothyroidism and its correlation with memory
function.
AB - Diffusion tensor tractography (DTT) was performed to determine the
microstructural changes in the white matter fibre tracts of hypothyroid patients
compared to controls and to correlate these changes with memory dysfunction
scores. DTT and Postgraduate Institute Memory Scale test were performed in eight
hypothyroid patients and eight healthy controls. Diffusion tensor imaging (DTI)
measures [fractional anisotropy (FA) and mean diffusivity (MD)] from all of the
major cerebral tracts were calculated and a comparison was made between the
patient group and controls. Pearson's correlation was performed between Memory
Dysfunction score and DTI measures. Significant changes in DTI measures were
observed in various white matter fibre tracts in hypothyroid patients compared to
controls. In hypothyroid patients, an inverse correlation of Memory Dysfunction
score with FA was observed in the right and left inferior fronto-occipital
fasciculus, whereas a positive correlation with MD was observed in the right
anterior thalamic radiation among all white matter tracts. These findings suggest
that microstructural changes in white matter fibres may contribute to the
underlying dysfunction in memory in hypothyroid patients.
PMID- 25131824
TI - The 2014 ACR Commission on Human Resources workforce survey.
AB - BACKGROUND: The ACR Commission on Human Resources conducts an annual electronic
survey during the first quarter of the year to better understand the present
workforce scenario for radiologists and allied health professionals. METHODS: The
Practice of Radiology Environment Database is used to identify group leaders who
are asked to complete an electronic survey developed by the Commission on Human
Resources. The survey asked 1,936 group leaders or their designates to report the
number of radiologists currently employed or supervised, the number hired in
2013, and the number they plan to hire in 2014 and 2017. The leaders were asked
to report the subspecialty area that was used as the main reason for hiring each
physician. RESULTS: The 22% response rate corresponds to 35% of all practicing
radiologists in the United States. The 2014 survey demonstrated that 78% of the
workforce is male and 22% is female and that 87% of the workforce works full
time. Fifty-three percent of the current workforce is in private practice and 47%
in varying forms of employment. The current workforce consists of 18% general
radiologists and 82% subspecialists. In 2013, 1,069 radiologists were hired. In
2014, 1,114 job opportunities are projected, and 1,131 estimated jobs are
forecast for 2017. CONCLUSIONS: Job opportunities for radiologists in 2014 remain
similar to those in 2013 and close to the numbers of residents completing
training programs in diagnostic radiology. Job opportunities remain available but
may not necessarily be in the subspecialty, geographic area, or type of practice
an individual most desires.
PMID- 25131825
TI - Radiologist manpower considerations and Imaging 3.0: effort planning for value
based imaging.
AB - Our specialty is seeking to establish the value of imaging in the longitudinal
patient-care continuum. We recognize the need to assess the value of our
contributions rather than concentrating primarily on generating revenue. This
recent focus is a result of both increased cost-containment efforts and
regulatory demands. Imaging 3.0 is a value-based perspective that intends to
describe and facilitate value-based imaging. Imaging 3.0 includes a broad set of
initiatives addressing the visibility of radiologists, and emphasizing quality
and safety oversight by radiologists, which are new directions of focus for us.
Imaging 3.0 also addresses subspecialty imaging and off-hours imaging, which are
existing areas of practice that are emblematic of inconsistent service delivery
across all hours. Looking to the future, Imaging 3.0 describes how imaging
services could be integrated into the framework of accountable care
organizations. Although all these efforts may be essential, they necessitate
manpower expenditures, and these efforts are not directly covered by revenue. If
we recognize the urgency of need in developing these concepts, we can justify the
manpower and staffing expenditures each organization is willing to shoulder in
reaching Imaging 3.0.
PMID- 25131826
TI - The importance of having zinc during in vitro maturation of cattle cumulus-oocyte
complex: role of cumulus cells.
AB - The aim of this study was to investigate the influence of zinc (Zn) on the health
of cumulus-oocyte complex (COC) during in vitro maturation (IVM). Experiments
were designed to evaluate the effect of Zn added to IVM medium on: DNA integrity,
apoptosis, cumulus expansion and superoxide dismutase (SOD) activity of cumulus
cells (CC). Also, role of CC on Zn transport during IVM was evaluated on oocyte
developmental capacity. DNA damage and early apoptosis were higher in CC matured
with 0 MUg/ml Zn compared with 0.7, 1.1 and 1.5 MUg/ml Zn (p < 0.05). Cumulus
expansion did not show differences in COC matured with or without Zn
supplementation (p > 0.05). Superoxide dismutase activity was higher in COC
matured with 1.5 MUg/ml Zn than with 0 MUg/ml Zn (p < 0.05). Cleavage and
blastocyst rates were recorded after IVM in three maturation systems: intact
COCs, denuded oocytes with cumulus cells monolayer (DO + CC) and denuded oocytes
(DO). Cleavage rates were similar when COC, DO + CC or DO were matured with 1.5
MUg/ml Zn compared with control group (p > 0.05). Blastocyst rates were
significantly higher in COC than in DO + CC and DO with the addition of 1.5
MUg/ml Zn during IVM (p < 0.01). Blastocyst quality was enhanced in COC and DO +
CC compared with DO when Zn was added to IVM medium (p < 0.001). The results of
this study indicate that Zn supplementation to IVM medium (i) decreased DNA
damage and apoptosis in CC; (ii) increased SOD activity in CC; (iii) did not
modify cumulus expansion and cleavage rates after in vitro fertilization; (iv)
improved subsequent embryo development up to blastocyst stage; and (v) enhanced
blastocyst quality when CC were present either in intact COC or in coculture
during IVM.
PMID- 25131827
TI - Vascular stiffness is a biomarker of global cardiovascular risk.
PMID- 25131828
TI - Shared and nonshared neural networks of cognitive and affective theory-of-mind: a
neuroimaging study using cartoon picture stories.
AB - Theory of mind (ToM) refers to the ability to represent one's own and others'
cognitive and affective mental states. Recent imaging studies have aimed to
disentangle the neural networks involved in cognitive as opposed to affective
ToM, based on clinical observations that the two can functionally dissociate. Due
to large differences in stimulus material and task complexity findings are,
however, inconclusive. Here, we investigated the neural correlates of cognitive
and affective ToM in psychologically healthy male participants (n = 39) using
functional brain imaging, whereby the same set of stimuli was presented for all
conditions (affective, cognitive and control), but associated with different
questions prompting either a cognitive or affective ToM inference. Direct
contrasts of cognitive versus affective ToM showed that cognitive ToM recruited
the precuneus and cuneus, as well as regions in the temporal lobes bilaterally.
Affective ToM, in contrast, involved a neural network comprising prefrontal
cortical structures, as well as smaller regions in the posterior cingulate cortex
and the basal ganglia. Notably, these results were complemented by a multivariate
pattern analysis (leave one study subject out), yielding a classifier with an
accuracy rate of more than 85% in distinguishing between the two ToM-conditions.
The regions contributing most to successful classification corresponded to those
found in the univariate analyses. The study contributes to the differentiation of
neural patterns involved in the representation of cognitive and affective mental
states of others.
PMID- 25131829
TI - Lentiviral-mediated silencing of glial fibrillary acidic protein and vimentin
promotes anatomical plasticity and functional recovery after spinal cord injury.
AB - In spinal cord injury (SCI), absence of functional recovery and lack of
spontaneous axonal regeneration are attributed, among other factors, to the
formation of a glial scar that forms both physical and chemical barriers. The
glial scar is composed mainly of reactive astrocytes that overexpress two
intermediate filament proteins, glial fibrillary acidic protein (GFAP) and
vimentin (VIM). To promote regeneration and sprouting of spared axons after
spinal cord trauma and with the objective of translation to clinics, we designed
an original in vivo gene transfer strategy to reduce glial scar formation after
SCI, based on the RNA interference (RNAi)-mediated inhibition of GFAP and VIM. We
first show that direct injection of lentiviral vectors expressing short hairpin
RNA (shRNA) against GFAP and VIM in a mouse model of SCI allows efficient and
specific targeting of astrocytes. We then demonstrate that the lentiviral
mediated and stable expression of shGFAP and shVIM leads to a strong reduction of
astrogliosis, improves functional motor recovery, and promotes axonal regrowth
and sprouting of spared axons. This study thus examplifies how the nonneuronal
environment might be a major target within the lesioned central nervous system to
promote axonal regeneration (and sprouting) and validates the use of lentiviral
mediated RNAi in SCI.
PMID- 25131831
TI - Massive schizophrenia genomics study offers new drug directions.
PMID- 25131832
TI - The CROWN Initiative: Journal editors invite researchers to develop core outcomes
in women's health.
PMID- 25131834
TI - Identification of a novel mutation in the polymerase delta 1 (POLD1) gene in a
lipodystrophic patient affected by mandibular hypoplasia, deafness, progeroid
features (MDPL) syndrome.
AB - OBJECTIVE: Progressive lipodystrophy is one of the major features of the rare
MDPL syndrome. Until now, 9 patients affected by this syndrome have been
described and a recent study identified in 4 of them an in-frame deletion
(Ser605del) of a single codon in the POLD1 gene. Sequence alterations of the
POLD1 gene at different sites have been previously reported in human colorectal
and endometrial carcinomas. MATERIALS/METHODS: A 48-year-old woman was admitted
to our department for the assessment of a previously diagnosed lipodystrophy. She
did not report a family history of diabetes or other metabolic disorders.
Hypertriglyceridemia was diagnosed incidentally when she was 25years old. At that
time she was also diagnosed with sensorineural bilateral hearing loss. At
physical examination she presented lipoatrophy affecting nearly the entire body,
mandibular hypoplasia, bird-like face, beaked nose, progeroid facial features,
with crowded teeth, small mouth and uvula. Abdominal ultrasound showed
hepatomegaly and hepatosteatosis. Fat mass index measured with DXA was
4.59kg/m(2), indicating a fat deficit; the oral glucose tolerance test showed an
impaired glucose tolerance. RESULTS: Sequence analysis of the entire coding
region of the POLD1 gene, disclosed a novel heterozygous mutation in exon 13
(R507C). CONCLUSION: The MDPL patient herein described harbors a novel mutation
in the exonuclease domain of POLD1. This new variant provides further evidence
for a role of POLD1 in the pathogenesis of MDPL. The mechanisms that link changes
at various sites of the protein with different diseases remain to be clarified.
PMID- 25131835
TI - Denosumab and osteonecrosis of the jaws - the pharmacology, pathogenesis and a
report of two cases.
AB - Denosumab (Amgen, Thousand Oaks, California, USA) is a new bone antiresorptive
agent used in patients with osteoporosis or metastatic cancer to the bones. As
with the bisphosphonates that are used as antiresorptive medications, denosumab
has been associated with osteonecrosis of the jaws (ONJ). Over the past two years
there has been an increase in the literature describing ONJ in patients receiving
agents such as denosumab. Due to promising study results that demonstrate the
effectiveness of denosumab in avoiding skeletal complications related to
osteoporosis and metastatic bone disease, more patients will receive denosumab in
the future. It is reported that this has the potential to become a comparable
challenge to bisphosphonate related osteonecrosis of the jaws (BRONJ) for
clinicians. This article describes the management of two patients that developed
ONJ while receiving denosumab, reviews the incidence of ONJ associated with
denosumab, and contrasts the pharmacokinetics of denosumab and the
bisphosphonates. The importance of avoiding interventional dental treatment until
denosumab has been withdrawn for six months cannot be overstated.
PMID- 25131836
TI - Comparison of iSED and Ves-Matic Cube 200 Erythrocyte Sedimentation Rate
Measurements With Westergren Method.
AB - BACKGROUND: The erythrocyte sedimentation rate (ESR) test is performed widely in
laboratories. Besides the traditional Westergren method, new methods have been
developed for ESR measurements. We aimed to compare the instruments using new
methods, iSED (Alcor Scientific) and Ves-Matic Cube 200 (Diesse Diagnostica
Senese, Italy) with the Westergren method. METHODS: Blood samples from 136
patients were taken into EDTA tubes for automated analyzers and citrated tubes
for Westergren method. Patients were divided into three groups- low, medium, and
high-according to their sedimentation rates. Precision, stability, and
interference studies of the methods were performed. RESULTS: The iSED
sedimentation method (n = 136) yielded a slope of (0.61-0.84), with an intercept
of (-2.32 to 1.89), which resulted in a mean bias of 13; and the Ves-Matic Cube
200 method (n = 136) yielded a slope of (0.85-1.00), with an intercept of (0.00
3.07), which resulted in a mean bias of 1.4 in Passing-Bablok regression analysis
compared to the reference method. CONCLUSION: iSED sedimentation showed a poor
correlation and a high bias (>10%) with the Westergren method, and Ves-Matic Cube
200 method showed a higher correlation and a lower bias than the iSED device when
compared with Westergren reference method. These instruments should be carefully
monitored.
PMID- 25131837
TI - Magnetic-structure-stabilized polarization in an above-room-temperature
ferrimagnet.
AB - Above-room-temperature polar magnets are of interest due to their practical
applications in spintronics. Here we present a strategy to design high
temperature polar magnetic oxides in the corundum-derived A2BB'O6 family,
exemplified by the non-centrosymmetric (R3) Ni3TeO6-type Mn(2+)2Fe(3+)Mo(5+)O6,
which shows strong ferrimagnetic ordering with TC = 337 K and demonstrates
structural polarization without any ions with (n-1)d(10)ns(0), d(0), or
stereoactive lone-pair electrons. Density functional theory calculations confirm
the experimental results and suggest that the energy of the magnetically ordered
structure, based on the Ni3TeO6 prototype, is significantly lower than that of
any related structure, and accounts for the spontaneous polarization (68 MUC cm(
2)) and non-centrosymmetry confirmed directly by second harmonic generation.
These results motivate new directions in the search for practical
magnetoelectric/multiferroic materials.
PMID- 25131838
TI - Using the virtual brain to reveal the role of oscillations and plasticity in
shaping brain's dynamical landscape.
AB - Spontaneous brain activity, that is, activity in the absence of controlled
stimulus input or an explicit active task, is topologically organized in multiple
functional networks (FNs) maintaining a high degree of coherence. These "resting
state networks" are constrained by the underlying anatomical connectivity between
brain areas. They are also influenced by the history of task-related activation.
The precise rules that link plastic changes and ongoing dynamics of resting-state
functional connectivity (rs-FC) remain unclear. Using the framework of the open
source neuroinformatics platform "The Virtual Brain," we identify potential
computational mechanisms that alter the dynamical landscape, leading to
reconfigurations of FNs. Using a spiking neuron model, we first demonstrate that
network activity in the absence of plasticity is characterized by irregular
oscillations between low-amplitude asynchronous states and high-amplitude
synchronous states. We then demonstrate the capability of spike-timing-dependent
plasticity (STDP) combined with intrinsic alpha (8-12 Hz) oscillations to
efficiently influence learning. Further, we show how alpha-state-dependent STDP
alters the local area dynamics from an irregular to a highly periodic alpha-like
state. This is an important finding, as the cortical input from the thalamus is
at the rate of alpha. We demonstrate how resulting rhythmic cortical output in
this frequency range acts as a neuronal tuner and, hence, leads to
synchronization or de-synchronization between brain areas. Finally, we
demonstrate that locally restricted structural connectivity changes influence
local as well as global dynamics and lead to altered rs-FC.
PMID- 25131833
TI - Predictive models of glucose control: roles for glucose-sensing neurones.
AB - The brain can be viewed as a sophisticated control module for stabilizing blood
glucose. A review of classical behavioural evidence indicates that central
circuits add predictive (feedforward/anticipatory) control to the reactive
(feedback/compensatory) control by peripheral organs. The brain/cephalic control
is constructed and engaged, via associative learning, by sensory cues predicting
energy intake or expenditure (e.g. sight, smell, taste, sound). This allows
rapidly measurable sensory information (rather than slowly generated internal
feedback signals, e.g. digested nutrients) to control food selection, glucose
supply for fight-or-flight responses or preparedness for digestion/absorption.
Predictive control is therefore useful for preventing large glucose fluctuations.
We review emerging roles in predictive control of two classes of widely
projecting hypothalamic neurones, orexin/hypocretin (ORX) and melanin
concentrating hormone (MCH) cells. Evidence is cited that ORX neurones (i) are
activated by sensory cues (e.g. taste, sound), (ii) drive hepatic production, and
muscle uptake, of glucose, via sympathetic nerves, (iii) stimulate wakefulness
and exploration via global brain projections and (iv) are glucose-inhibited. MCH
neurones are (i) glucose-excited, (ii) innervate learning and reward centres to
promote synaptic plasticity, learning and memory and (iii) are critical for
learning associations useful for predictive control (e.g. using taste to predict
nutrient value of food). This evidence is unified into a model for predictive
glucose control. During associative learning, inputs from some glucose-excited
neurones may promote connections between the 'fast' senses and reward circuits,
constructing neural shortcuts for efficient action selection. In turn, glucose
inhibited neurones may engage locomotion/exploration and coordinate the required
fuel supply. Feedback inhibition of the latter neurones by glucose would ensure
that glucose fluxes they stimulate (from liver, into muscle) are balanced.
Estimating nutrient challenges from indirect sensory cues may become more
difficult when the cues become complex and variable (e.g. like human foods
today). Consequent errors of predictive glucose control may contribute to obesity
and diabetes.
PMID- 25131830
TI - Histone deacetylases and their inhibitors in cancer, neurological diseases and
immune disorders.
AB - Epigenetic aberrations, which are recognized as key drivers of several human
diseases, are often caused by genetic defects that result in functional
deregulation of epigenetic proteins, their altered expression and/or their
atypical recruitment to certain gene promoters. Importantly, epigenetic changes
are reversible, and epigenetic enzymes and regulatory proteins can be targeted
using small molecules. This Review discusses the role of altered expression
and/or function of one class of epigenetic regulators--histone deacetylases
(HDACs)--and their role in cancer, neurological diseases and immune disorders. We
highlight the development of small-molecule HDAC inhibitors and their use in the
laboratory, in preclinical models and in the clinic.
PMID- 25131840
TI - Nomenclature for factors of the HLA system, April update 2014.
PMID- 25131839
TI - Lipid-lowering effects of curcumin in patients with metabolic syndrome: a
randomized, double-blind, placebo-controlled trial.
AB - Human studies of curcumin extract on lipid-lowering effect have not been
completely investigated and have had controversy results. This study tested the
effect of daily curcumin extract for 12 weeks on weight, glucose, and lipid
profiles in patients with metabolic syndrome. Sixty-five patients were randomized
into two groups; 33 patients taking curcumin extract capsule (630 mg thrice
daily) and 32 patients taking a placebo capsule thrice daily for 12 weeks. At 12
weeks after the curcumin extract consumption, the level of high-density
lipoprotein cholesterol (HDL-C) significantly increased from 40.96 +/- 8.59 to
43.76 +/- 2.79 mg/dL (p < 0.05), and the level of low-density lipoprotein
cholesterol (LDL) was significantly reduced (120.55 +/- 36.81 to 106.51 +/- 25.02
mg/dL, p < 0.05). The triglyceride-lowering effect, a reduction of 65 mg/dL, was
also found in this study. In subgroups analysis, the consumption of curcumin may
have a lowering cholesterol effect in male patients and an increasing HDL-C
effect in female patients, both of which result in a decrease of T-Chol/HDL-C
ratio. The intake of the curcumin extract of 1890 mg/day for 12 weeks was
associated with lipid-lowering effect but did not improve weight and glucose
homeostasis in the patients with metabolic syndrome. Daily curcumin consumption
may be an alternative choice to modify cholesterol-related parameters, especially
in metabolic syndrome patients.
PMID- 25131841
TI - Modeling radiocesium transport from a river catchment based on a physically-based
distributed hydrological and sediment erosion model.
AB - The accident at the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) in March 2011
resulted in the deposition of large quantities of radionuclides, such as (134)Cs
and (137)Cs, over parts of eastern Japan. Since then high levels of radioactive
contamination have been detected in large areas, including forests, agricultural
land, and residential areas. Due to the strong adsorption capability of
radiocesium to soil particles, radiocesium migrates with eroded sediments,
follows the surface flow paths, and is delivered to more populated downstream
regions and eventually to the Pacific Ocean. It is therefore important to
understand the transport of contaminated sediments in the hydrological system and
to predict changes in the spatial distribution of radiocesium concentrations by
taking the land-surface processes related to sediment migration into
consideration. In this study, we developed a distributed model to simulate the
transport of water and contaminated sediment in a watershed hydrological system,
and applied this model to a partially forested mountain catchment located in an
area highly contaminated by the radioactive fallout. Observed discharge, sediment
concentration, and cesium concentration measured from June 2011 until December
2012 were used for calibration of model parameters. The simulated discharge and
sediment concentration both agreed well with observed values, while the cesium
concentration was underestimated in the initial period following the accident.
This result suggests that the leaching of radiocesium from the forest canopy,
which was not considered in the model, played a significant role in its transport
from the catchment. Based on the simulation results, we quantified the long-term
fate of radiocesium over the study area and estimated that the effective half
life of (137)Cs deposited in the study area will be approximately 22 y due to the
export of contaminated sediment by land-surface processes, and the amount of
(137)Cs remaining in the catchment will be reduced to 39% of the initial total
within 30 y after contamination. This study provides a perspective on the
transport of suspended sediments and radiocesium in catchments with similar land
use and radiocesium contamination.
PMID- 25131843
TI - Effect of passive polarizing three-dimensional displays on surgical performance
for experienced laparoscopic surgeons.
AB - BACKGROUND: Although the potential benefits of stereoscopic laparoscopy have been
recognized for years, the technology has not been adopted because of poor
operator tolerance. Passive polarizing projection systems, which have
revolutionized three-dimensional (3D) cinema, are now being trialled in surgery.
This study was designed to see whether this technology resulted in significant
performance benefits for skilled laparoscopists. METHODS: Four validated
laparoscopic skills tasks, each with ten repetitions, were performed by 20
experienced laparoscopic surgeons, in both two-dimensional (2D) and 3D
conditions. The primary outcome measure was the performance error rate; secondary
outcome measures were time for task completion, 3D motion tracking (path length,
motion smoothness and grasping frequency) and workload dimension ratings of the
National Aeronautics and Space Administration (NASA) Task Load Index. RESULTS:
Surgeons demonstrated a 62 per cent reduction in the median number of errors and
a 35 per cent reduction in median performance time when using the passive
polarizing 3D display compared with the 2D display. There was a significant 15
per cent reduction in median instrument path length, an enhancement of median
motion smoothness, and a 15 per cent decrease in grasper frequency with the 3D
display. Participants reported significant reductions in subjective workload
dimension ratings of the NASA Task Load Index following use of the 3D displays.
CONCLUSION: Passive polarizing 3D displays improved both the performance of
experienced surgeons in a simulated setting and surgeon perception of the
operative field. Although it has been argued that the experience of skilled
laparoscopic surgeons compensates fully for the loss of stereopsis, this study
indicates that this is not the case. Surgical relevance The potential benefits of
stereoscopic laparoscopy have been known for years, but the technology has not
been adopted because of poor operator tolerance. The first laparoscopic operation
was carried out using a prototype passive polarizing laparoscopic system in 2010.
This is new three-dimensional (3D) technology offers a real option for 3D
laparoscopic surgery where previous systems have failed. This study is the first
to have been carried out using this technology. It is essential that new
technologies are adopted only when there is robust evidence to support their use.
Currently, there are concerns about the use of robotic technologies and whether
advantages exist for patient care. If there are advantages, 3D must be playing a
significant role. If so, perhaps the technology under investigation here offers
potential to a greater spectrum of surgeons, as well as being a more affordable
option.
PMID- 25131842
TI - Anatomical landmarks for the localization of the greater palatine foramen--a
study of 1200 head CTs, 150 dry skulls, systematic review of literature and meta
analysis.
AB - Accurate knowledge of greater palatine foramen (GPF) anatomy is necessary when
performing a variety of anaesthesiological, dental or surgical procedures. The
first aim of this study was to localize the GPF in relation to multiple
anatomical landmarks. The second aim was to perform a systematic review of
literature, and to conduct a meta-analysis on the subject of GPF position to aid
clinicians in their practice. One-hundred and fifty dry, adult, human skulls and
1200 archived head computed tomography scans were assessed and measured in terms
of GPF relation to other anatomical reference points. A systematic literature
search was performed using the PubMed, Embase and Web of Science databases, and a
meta-analysis on the subject of GPF relation to the maxillary molars was
conducted. On average, in the Polish population, the GPF was positioned 15.9 +/-
1.5 mm from the midline maxillary suture (MMS), 3.0 +/- 1.2 mm from the alveolar
ridge (AR) and 17.0 +/- 1.5 mm from the posterior nasal spine (PNS); 74.7% of GPF
were positioned opposite the third maxillary molar (M3). Twenty-seven studies
were included in the systematic review and 23 in the meta-analysis (n = 6927
GPF). The pooled prevalence of the GPF being positioned opposite the M3 was 63.9%
(95% confidence interval = 56.6-70.9%). Concluding, the GPF is most often located
opposite the M3 in the majority of the world's populations. The maxillary molars
are the best landmarks for locating the GPF. In edentulous patients the most
useful points for approximating the position of the GPF are the AR, MMS and PNS.
This study introduces an easy and repeatable classification to reference the GPF
to the maxillary molars.
PMID- 25131844
TI - Some problems with determining the reliability of the EQ-5D-3L: commentary to
"Value of EQ-5D in Mexican city older population with and without dementia (SADEM
study)".
PMID- 25131845
TI - Lysophosphatidic acid stimulates cell migration of satellite cells. A role for
the sphingosine kinase/sphingosine 1-phosphate axis.
AB - Regulation of the motility of skeletal muscle precursor cells, such as satellite
cells, is critically important for their proper recruitment at the site of tissue
damage, and ultimately for its correct repair. Here we show that lysophosphatidic
acid (LPA), which is well-recognized as a powerful bioactive agent, strongly
stimulates cell migration of activated murine satellite cells. The biological
effect exerted by LPA was found to be induced via activation of LPA1 and LPA3 ,
being abolished by cell treatment with the antagonist Ki16425, and severely
impaired by siRNA-mediated down-regulation of the two receptor isoforms. In
contrast, silencing of LPA2 potentiated the stimulation of cell motility by LPA,
suggesting that it is negatively coupled to cell migration. Pharmacological
inhibition of both sphingosine kinase (SK) isoforms using VPC96047, or the
selective blocking of SK1 using VPC96091, abolished cell responsiveness to LPA;
in agreement, gene silencing of SK1 or SK2 significantly reduced the biological
effect of LPA. Moreover, the LPA-dependent stimulation of cell chemotaxis was
found to be impaired by down-regulation of the sphingosine 1-phosphate (S1P)
receptors S1P1 or S1P4 by specific siRNAs. In summary, the results obtained
support the notion that the sphingosine kinase/sphingosine 1-phosphate (SK/S1P)
axis is critically involved in the mechanism by which LPA elicits its pro
migratory action. This study provides compelling new information on the
regulatory mechanisms of satellite cell motility, and reinforces the view that
the SK/S1P signaling pathway plays a crucial role in the control of skeletal
muscle precursor cell biology.
PMID- 25131846
TI - The prevalence of keratoconus in a young population in Mashhad, Iran.
AB - PURPOSE: To determine the prevalence of keratoconus and some associated factors
in the students of Mashhad University of Medical Sciences, Iran. METHOD: In this
cross sectional study, multistage cluster sampling was used to select the
participants. All participants underwent retinoscopy, slit lamp examination,
topography with the TMS-4 and corneal assessment with the Orbscan II. The
diagnosis of keratoconus was based on both clinical evidence and the results of
corneal imaging. RESULTS: Of 1280 selected students, 1073 agreed to participate
in the study, and of those who agreed, 1027 fulfilled the inclusion criteria.
42.5% of the study population was male with a mean age of 26.1 +/- 2.3 years. The
prevalence of keratoconus was 2.5% (n = 26) (95% confidence interval, CI 1.6
3.5). Eighteen students (69%) had bilateral keratoconus. Imaging of the cornea
revealed that 70% of the keratoconics had nipple cones and the remaining had
asymmetric bow-tie patterns. The prevalence of keratoconus was not significantly
associated with age or gender (p > 0.05). In a multiple logistic regression
model, family history (OR = 11.4, 95% CI: 2.5-51.3) and eye rubbing (OR = 6.3,
95% CI: 1.6-24.3) were significantly correlated with keratoconus. CONCLUSIONS:
These results taken together with recent studies in the area suggest that
keratoconus may have a higher prevalence in the Middle East and Asia than in
Western Countries.
PMID- 25131847
TI - Genetic testing and corresponding services among individuals with autism spectrum
disorder (ASD).
AB - The purpose of this study was to assess use of genetic testing and corresponding
genetic services for children with Autism Spectrum Disorder (ASD). Survey data
from 397 parents of individuals with ASD was collected using the Center for
Autism and Related Disabilities client registry. Participants reported that 41.2%
of the individuals with ASD had undergone any type of genetic testing. However,
only 21.3% of individuals with ASD had been referred to a genetics specialist.
Diagnosis and level of functioning were significantly associated with both
referral to a genetics specialist and having undergone any genetic testing. In
addition, Hispanic ancestry was associated with increased referral to genetic
testing. Concerns about the limited benefits of genetic testing and prohibitive
costs were potential barriers to pursuing genetic testing. Overall, low numbers
of individuals with ASD have a history of undergoing genetic testing or receiving
genetic services. Possible reasons include low referral rates as well as concerns
by parents about cost and relevance, and lack of availability. These findings
confirm the historical trend for providing genetic testing and genetic services
to those with the greatest impairments.
PMID- 25131848
TI - Evidence accumulates on the association between topiramate use early in pregnancy
and the risk of oral clefts.
PMID- 25131851
TI - Dynamic changes in metabolic profiles of rats subchronically exposed to
mequindox.
AB - Mequindox is widely used as an antibacterial veterinary drug and a feeding
additive for farm animals in China. Although its toxicity has been widely
studied, little is known regarding the metabolic effects of subchronic exposure
to mequindox, which is vital for the health of meat producing livestock. Here, we
characterized the dose- and time-dependent metabolic alterations in female Wistar
rats subchronically exposed to mequindox through dietary supplementation at the
level of 40, 110 and 280 mg kg(-1) for 13 weeks, employing a NMR based
metabonomics approach with supplementary information from serum clinical
chemistry. We found that urinary metabolic profiles were significantly affected
in all dosed groups during the supplementation period; plasma and hepatic
metabolic profiles were significantly affected only in rats dosed with moderate
and high levels of mequindox. We also observed a return to control levels, for
the profiles of urine and liver, at all dose levels after a two weeks washout
period. However, this was not the case for the metabolic profiles of plasma from
rats dosed at high levels. At the molecular level, we showed that subchronic
exposure to mequindox resulted in tricarboxylic acid cycle (TCA cycle)
stimulation, suppression of glycolysis, and promotion of gluconeogenesis and
lipid oxidation in rats. In addition, subchronic exposure to mequindox induced
oxidative stress in rats. Furthermore, a disturbance of gut microbiota,
manifested by alterations in the urinary excretion of hippurate,
phenylacetylglycine, 3-(3-hydroxyphenyl)propionate, p-cresol glucuronide,
methylamine, dimethylamine, and formate, was associated with mequindox exposure.
The present study provided important holistic metabolic information on the
effects of subchronic dosage of mequindox on rats, which is useful for evaluating
the safety of mequindox usage in meat producing animals.
PMID- 25131852
TI - Role of hematopoietic stem cell transplantation in multiple myeloma.
AB - High-dose therapy followed by autologous stem cell transplantation (ASCT) has
been the standard frontline consolidative therapy for patients with newly
diagnosed multiple myeloma (MM) for > 2 decades. This approach has resulted in
higher complete response (CR) rates and increased event-free survival and overall
survival (OS) compared with conventional chemotherapy. The emergence of novel
agent-based therapy combined with ASCT has revolutionized MM therapy by improving
the CR rates and OS, raising questions concerning the role of hematopoietic stem
cell transplantation in this setting.
PMID- 25131850
TI - In utero and early childhood exposure to arsenic decreases lung function in
children.
AB - The lung is a target organ for adverse health outcomes following exposure to As.
Several studies have reported a high prevalence of respiratory symptoms and
diseases in subjects highly exposed to As through drinking water; however, most
studies to date has been performed in exposed adults, with little information on
respiratory effects in children. The objective of the study was to evaluate the
association between urinary levels of As and its metabolites with lung function
in children exposed in utero and in early childhood to high As levels through
drinking water. A total of 358 healthy children were included in our study.
Individual exposure was assessed based on urinary concentration of inorganic As.
Lung function was assessed by spirometry. Participants were exposed since
pregnancy until early childhood to an average water As concentration of 152.13 ug
l-1. The mean urinary As level registered in the studied subjects was 141.2 ug l
1 and only 16.7% had a urinary concentration below the national concern level.
Forced vital capacity was significantly decreased in the studied population and
it was negatively associated with the percentage of inorganic As. More than 57%
of the subjects had a restrictive spirometric pattern. The urinary As level was
higher in those children with restrictive lung patterns when compared with the
levels registered in subjects with normal spirometric patterns. Exposure to As
through drinking water during in utero and early life was associated with a
decrease in forced vital capacity and with a restrictive spirometric pattern in
the children evaluated.
PMID- 25131853
TI - Isolated mesenteric CD20-positive myeloid sarcoma.
PMID- 25131854
TI - Clinicopathologic analysis of POEMS syndrome and related diseases.
AB - BACKGROUND: POEMS syndrome, a rare paraneoplastic disease, is related to multiple
organs, multiple systems, and multiple disciplines and can be mistaken for other
disorders. Consequently, the diagnoses are often delayed. In this work we studied
the clinicopathologic characteristics of the POEMS syndrome to improve early
diagnosis to prevent irreversible damage. PATIENTS AND METHODS: We conducted a
clinicopathologic analysis of 9 cases of POEMS and made a differential diagnosis
with related diseases. RESULTS: The patients with POEMS syndrome were shown to
have complicated clinical characteristics, including peripheral neuropathy,
organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin
changes, extravascular volume overload, sclerotic bone lesions, thrombocytosis,
and Castleman disease. POEMS syndrome shared many elements with other diseases
and the key way to differentiate them was to determine whether there were other
fundamental POEMS syndrome symptoms or signs. The level of M-protein in serum and
plasma cells in bone marrow of POEMS patients was lower than that of patients
with multiple myeloma (MM). Sclerotic bone lesions were a distinctive feature in
patients with POEMS, compared with in those with MM. CONCLUSION: Some unique
clinicopathologic characteristics of POEMS syndrome can be used for differential
diagnosis. This study provides increased awareness of POEMS syndrome.
PMID- 25131855
TI - Complete remission of VZV reactivation treated with valganciclovir in a patient
with total lymphocyte depletion and acute kidney injury after allogeneic bone
marrow transplantation.
AB - Varicella zoster virus (VZV), a threat for hematopoietic stem cell
transplantation (HSCT) recipients, is still one of the most common viral
pathogens that affect these patients with a reported incidence ranging between
17% and 50% in the post transplantation period. Valganciclovir (V-GCV), a valine
ester pro-drug of GCV orally administrable, has recently shown great activity
against CMV infections, but there are no reports of its clinical efficacy against
VZV. We here report a case history of a patient with positive serologic test for
VZV, who underwent allogeneic HSCT and developed an atypical varicella-like
illness. First-line therapy with foscarnet had to be discontinued due rapid
development of renal impairment (creatinine: 2.60 mg/dL, urea: 130.6 mg/dL) and
therefore was switched to V-GCV. The renal impairment and skin lesions of the
patient fully recovered after few days of therapy, even though the patient had
complete lymphocyte depletion. This is the first case of a patient with
chickenpox-like illness treated successfully with V-GCV.
PMID- 25131856
TI - Hepatitis C virus infection in China: an emerging public health issue.
AB - Hepatitis C virus now represents a global viral pandemic and is the fourth most
commonly reported infectious disease in China. Information on China's national
HCV epidemic was limited to cross -sectional seroprevalence studies of special
populations, and a national surveillance effort had been launched to inform
prevention and control. We analysed novel data from two national databases: (i)
China's national medical HCV case report system and (ii) the national disease
sentinel surveillance system. Between 1997 and 2012, reporting incidence of
medical cases for HCV infection rose from 0.7 to 15.0 cases per 100 000 with the
largest burden of disease concentrated among individuals over 35 years of age,
rural residents and those tested as part of routine screening. Between 2010 and
2012, disease sentinel surveillance identified the highest HCV seropositive rates
among persons who use drugs and haemodialysis patients, with far lower but not
negligible rates among sexually active population. The concentration of cases
among older age groups is consistent with past studies of age-specific prevalence
rates in Asia. Differences across regions and testing modes suggest diverse
biological and social forces driving the spread of HCV in China. Surveillance
data show ongoing transmission, particularly among persons who use drugs and
persons undergoing invasive medical treatments, particularly haemodialysis.
Improvements in case detection and data reporting systems will be critical for
understanding current drivers of transmission and identifying key areas for
prevention.
PMID- 25131857
TI - Informal social networks of people with profound intellectual and multiple
disabilities: relationship with age, communicative abilities and current living
arrangements.
AB - BACKGROUND: People with profound intellectual and multiple disabilities (PIMD)
have limited informal social contacts. Research to determine the factors which
can positively influence establishing sound informal social contacts is required.
MATERIALS AND METHODS: Regression analysis for 200 people with PIMD was used to
analyse how age, communicative abilities and current living arrangements were
related to the number and frequency of their contacts. RESULTS: Only age was
negatively related to both the number and frequency of social contacts. Current
living arrangements related only to the frequency of contacts. Communicative
abilities related to neither. CONCLUSIONS: Like people with intellectual
disabilities, age and living arrangements are related to the informal social
networks of people with PIMD. However, for people with PIMD, these networks are
already more limited. Therefore, professionals need to be attentive to the
maintenance and/or expansion of the social networks of people with PIMD at an
early stage.
PMID- 25131859
TI - Expression, purification, and micelle reconstitution of antimicrobial piscidin 1
and piscidin 3 for NMR studies.
AB - Piscidin 1 and piscidin 3, which were discovered in the mast cells of hybrid
striped sea bass, are homologous antimicrobial peptides that are active against
drug-resistant bacteria. Piscidin 1, the more antimicrobial and hemolytic
peptide, also has anti-HIV-1 and anti-cancer properties. To understand the
reasons underlying the different biological activities of the two peptides and
identify principles to design antimicrobial drugs with improved efficacy and
lower toxicity, their atomic-level structures must be obtained under
physiologically-relevant conditions. High-resolution backbone structures of both
piscidins exist in the presence of hydrated phospholipid bilayers but full
structures that include the side chains are missing. Here, the piscidins 1 and 3
genes were cloned into the TrpLE vector. The corresponding TrpLE-piscidin fusion
partners were expressed in Escherichiacoli and recovered from inclusion bodies.
Following steps that included Ni-NTA chromatography, cyanogen bromide cleavage of
the fusion proteins, and reverse-phase HPLC, purified piscidins 1 and 3 were
recovered in very good yield and characterized by NMR. High quality (15)N-(1)H
HSQC spectra of piscidins 1 and 3 bound to SDS micelles were collected,
demonstrating the feasibility of producing and purifying the isotopically-labeled
piscidin peptides required to determine their full structures by multidimensional
NMR spectroscopy.
PMID- 25131858
TI - Expression of recombinant human mast cell chymase with Asn-linked glycans in
glycoengineered Pichia pastoris.
AB - Recombinant human mast cell chymase (rhChymase) was expressed in secreted form as
an active enzyme in the SuperMan5 strain of GlycoSwitch(r) Pichia pastoris, which
is engineered to produce proteins with (Man)5(GlcNAc)2 Asn-linked glycans. Cation
exchange and heparin affinity chromatography yielded 5mg of active rhChymase per
liter of fermentation medium. Purified rhChymase migrated on SDS-PAGE as a single
band of 30 kDa and treatment with peptide N-glycosidase F decreased this to 25
kDa, consistent with the established properties of native human chymase
(hChymase). Polyclonal antibodies against hChymase detected rhChymase by Western
blot. Active site titration with Eglin C, a potent chymase inhibitor, quantified
the concentration of purified active enzyme. Kinetic analyses with succinyl-Ala
Ala-Pro-Phe (suc-AAPF) p-nitroanilide and thiobenzyl ester synthetic substrates
showed that heparin significantly reduced KM, whereas heparin effects on kcat
were minor. Pure rhChymase with Asn-linked glycans closely resembles hChymase.
This bioengineering approach avoided hyperglycosylation and provides a source of
active rhChymase for other studies as well as a foundation for production of
recombinant enzyme with human glycosylation patterns.
PMID- 25131860
TI - Expression and biochemical characterization of recombinant human epididymis
protein 4.
AB - Whey acidic proteins (WAP) belong to a large gene family of antibacterial
peptides that perform critical immune system functions. The function of human
epididymis protein 4 (HE4), a 124-amino acid long polypeptide that has two whey
acidic protein four-disulfide core (WFDC) domains, is not well studied. Here, a
fusion gene encoding the HE4 protein fused to an IgG1 Fc domain was constructed.
The recombinant HE4 protein was expressed as a secretory protein in Pichia
pastoris and mammalian HEK293-F cells and was subsequently purified. Our data
suggested that the HE4 protein produced by these two expression systems bound to
both gram-negative and gram-positive bacteria, but demonstrated slightly
inhibitory activity towards the growth of Staphylococcus aureus. Moreover, HE4
exhibited proteinase inhibitory activity towards trypsin, elastase, matrix
metallopeptidase 9, and the secretory proteinases from Bacillus subtilis. The
effects of glycosylation on the biochemical characterization of HE4 were also
investigated. LC-ESI-MS glycosylation analysis showed that the high-mannose
glycosylated form of HE4 expressed by P. pastoris has lower biological activity
when compared to its complex-glycosylated form produced from HEK293-F cells. The
implications of this are discussed, which may be provide theoretical basis for
its important role in the development of cancer and innate immune system.
PMID- 25131861
TI - Depression, anxiety and self-care behaviours of young adults with Type 2
diabetes: results from the International Diabetes Management and Impact for Long
term Empowerment and Success (MILES) Study.
AB - AIM: Young adults with Type 2 diabetes have higher physical morbidity and
mortality than other diabetes sub-groups, but differences in psychosocial
outcomes have not yet been investigated. We sought to compare depression and
anxiety symptoms and self-care behaviours of young adults with Type 2 diabetes
with two matched control groups. METHODS: Using cross-sectional survey data from
the Australian and Dutch Diabetes Management and Impact for Long-term Empowerment
and Success (MILES) studies, we matched 93 young adults (aged 18-39 years) with
Type 2 diabetes (case group) with: (i) 93 older adults ( >= 40 years) with Type 2
diabetes (Type 2 diabetes control group; matched on country, gender, education,
diabetes duration and insulin use) and (ii) 93 young adults with Type 1 diabetes
(Type 1 diabetes control group; matched on country, gender, age and education).
Groups were compared with regard to depression symptoms (nine-item Patient Health
Questionnaire), anxiety symptoms (seven-item Generalised Anxiety Disorder
questionnaire) and frequency of selected self-care behaviours (single item per
behaviour). RESULTS: Participants in the case group had higher depression scores
(Cohen's d = 0.40) and were more likely to have clinically meaningful depressive
symptoms (Cramer's V = 0.23) than those in the Type 2 diabetes control group.
Participants in the case group had statistically equivalent depression scores to
the Type 1 diabetes control group. The groups did not differ in anxiety scores.
Those in the case group were less likely than both control groups to take insulin
as recommended (Cramer's V = 0.24-0.34), but there were no significant
differences between the groups in oral medication-taking. The case group were
less likely than the Type 2 diabetes control group to eat healthily (Cramer's V =
0.16), and less likely than the Type 1 diabetes control group to be physically
active (Cramer's V = 0.15). CONCLUSIONS: Our results suggest that Type 2 diabetes
is as challenging as Type 1 diabetes for young adults and more so than for older
adults. Young adults with Type 2 diabetes may require more intensive
psychological and self-care support than their older counterparts.
PMID- 25131862
TI - [Carcinoma unknown primary-clinical practice].
AB - Carcinomas of unknown primary are cancers that are pathologically diagnosed as
carcinomas based on the findings of metastatic lesion biopsy but in which the
primary site remains unknown even after thorough and detailed examinations.In the
clinical setting, pathological diagnosis and diagnostic imaging are very
important for cases of carcinoma of unknown primary. When examinations do not
identify the primary tumor, carcinoma cases are treated as carcinoma of unknown
primary.In clinical practice, it is very important not to miss cases of favorable
prognosis group, which is 20% of unknown cancer. Recently, microarray studies
have been performed for cases of carcinoma of unknown primary.
PMID- 25131863
TI - [New era of the treatment of CRPC in Japan].
AB - In Y2014, several new agents targeted to castration resistant(recurrent)prostate
cancer; CRPC, are approved in Japan. Although such good news comes 2-3 years
behind Western, it may improve the outcomes of the CRPC patients in Japan. In
this issue, enzalutamide, abiraterone, and cabazitaxel are discussed by each
experts from the productive industries. In addition, the experts from urological
field and medical oncology field describe the role of each discipline.
PMID- 25131864
TI - [Enzalutamide-a novel androgen receptor inhibitor that provides treatment options
for patients with castration-resistant prostate cancer].
AB - The recent emergence of new hormonal or chemotherapeutic drugs has resulted in a
paradigm shift in the treatment of castration-resistant prostate cancer(CRPC).
Enzalutamide is a rationally designed, orally administered androgen
receptor(AR)inhibitor. It inhibits multiple points in the androgen receptor
signalling pathway, which is considered an important driver of CRPC, including
the inhibition of androgen binding to the AR, nuclear translocation of the AR
complex, and binding of the AR complex to deoxyribonucleic acid(DNA). Unlike
other anti-androgens(such as bicalutamide), enzalutamide does not act as a
partial AR agonist. The first in human phase I/II trial was conducted in the
United States in both chemotherapy-naive patients and postchemotherapy patients
with progressive metastatic CRPC(mCRPC). The results showed encouraging antitumor
activity of enzalutamide by considering all outcomes assessed in the trial. The
first reported phase III trial was a randomized, double-blind, placebo
controlled, multinational study involving 1,199 patients with mCRPC that
progressed even after docetaxel therapy(AFFIRM trial). Enzalutamide was
associated with significant benefits over the placebo considering time-to-event
outcomes(i.e. prolonged overall survival[OS], delayed time to prostatic specific
antigen[PSA]progression[TTPP], prolonged radiographic progression free
survival[rPFS], time to the first skeletal related event[SRE])as well as
objective response outcomes(i.e. PSA, soft tissue, and quality of life[QOL]). On
the basis of the AFFIRM results, Astellas and Medivation filed a new drug
application with the United States Food and Drug Administration and the European
Medicines Agency in 2012, and obtained their approval. Another phaseI/II
enzalutamide trial was conducted in both chemotherapy-naive patients and post
chemotherapy pa- tients with progressive mCRPC. Enzalutamide at a dose of
160mg/day was well tolerated, and it showed pharmacokinetic characteristics,
adverse events, and anti-tumor activity profiles similar to that of the non
Japanese population. On the basis of the results of the studies summarized above,
a new drug application was submitted to the Ministry of Health, Labour, and
Welfare of Japan in May 2013 and obtained the approval in Mar 2014. The second
phase III trial was a randomized, double-blind, placebo-controlled, multinational
study of 1,717 chemotherapy- naive patients with CRPC(PREVAIL trial). An interim
analysis recently demonstrated the significant benefits of enzalutamide over the
placebo considering both OS and rPFS. In light of these results, the Independent
Data Monitoring Committee (IDMC)advised terminating the study early, and
suggested treating the patients in the placebo group with enzalutamide. This
paper reviews the developmental history of enzalutamide, its pharmacokinetic and
pharmacodynamic characteristics, as well as available efficacy and tolerability
data yielded in clinical trials of patients with CRPC.
PMID- 25131865
TI - [Abiraterone acetate(ZYTIGA(r))-development and literature review].
AB - Abiraterone acetate(AA)has been approved in more than 80 countries for the
treatment of patients with metastatic castration-resistant prostate
cancer(mCRPC). In July 2013, a marketing approval application for AA was
submitted to the Japanese Ministry of Health, Labour, and Welfare. AA is a
selective inhibitor of CYP17A1, a crucial enzyme for androgen biosynthesis. AA
exerts its anti-tumor activity by directly inhibiting androgen production at all
three sources, i. e., the testes, adrenal glands, and tumor itself. Data from
international phase III studies and phase I and II studies in Japan have
indicated that AA improves the overall survival and quality of life(QoL)of
patients with mCRPC. Herein, we have summarized the development of AA and the
results of important international and local clinical trials in Japan. In
addition, the effect of food on AA bioavailability, concomitant steroid use, and
liver function test abnormalities have been discussed regarding the appropriate
use of AA.
PMID- 25131866
TI - [Cabazitaxel--a next-generation taxane for the treatment of patients with
metastatic castration-resistant prostate cancer].
AB - Prostate cancer is a heterogeneous disease that responds variably to available
agents, particularly androgen receptor(AR)- targeting agents. In preclinical
models, cabazitaxel, a second-generation taxane, demonstrated enhanced antitumor
activity when compared with docetaxel. In subsequent clinical trials, cabazitaxel
was associated with pharmacokinetic, safety, and tolerability profiles consistent
with those of previous taxanes. In the pivotal phase III study(TROPIC;
NCT00417079), cabazitaxel led to significantly improved overall survival in
patients with metastatic castration-resistant prostate cancer(mCRPC), compared
with mitoxantrone, when both were administered in combination with
prednisone/prednisolone(median survival: 15.1 months[95%confidence interval(CI):
14.1-16.3]vs 12.7 months[95% CI: 11.6-13.7], hazard ratio(HR): 0.70[95% CI: 0.59
0.83], p<0.0001), and it also extended progression-free survival. Furthermore, a
long-term analysis of the TROPIC trial revealed that the survival benefit with
cabazitaxel was maintained at 2 years, with 60(15.9%)patients in the cabazitaxel
group and 31(8.2%)patients in the mitoxantrone group surviving for B2 years(odds
ratio: 2.11, 95% CI: 1.33-3.33). Cabazitaxel also provides pain palliation
similar to that provided by using mitoxantrone. The safety profile of cabazitaxel
is consistent with that of first-generation taxanes, and
gastrointestinal(predominantly diarrhea)and hematologic(mainly
neutropenia)adverse events are the most frequently reported. Clinical trial data
suggest that these events can be managed with careful monitoring and dose
reduction where necessary. In addition, treatment with granulocyte colony
stimulating factor(G-CSF)can mitigate hematologic adverse events, whereas
supportive treatment with antiemetic and antidiarrheal agents may ameliorate
gastrointestinal symptoms. The treatment paradigm for mCRPC is evolving rapidly
with the emergence of data for new agents, leading to maximization of patient
benefits. The proven efficacy and tolerability profiles of cabazitaxel suggest
the promising role of this agent within this paradigm.
PMID- 25131867
TI - [Role of urologists in the era of new treatment modalities for CRPC in Japan].
AB - New medical treatment modalities for castration resistant prostate cancer(CRPC),
including hormonal therapy and chemotherapy, will be approved in Japan. Here, we
discuss the management of these new treatment strategies by urologists.
PMID- 25131868
TI - [Roles of medical oncologists in the new era of CRPC therapy in Japan].
AB - Currently, the standard therapy for advanced prostate cancer is endocrine
therapy(luteinizing hormone-releasing hormone [LH-RH]agonists alone or LH
RHagonists plus antiandrogens). However, most patients eventually become
resistant to these therapies as well as castration therapy. New endocrine
therapies for castration-resistant prostate cancer(CRPC)have been developed.
Abiraterone, a CYP17 inhibitor, and enzalutamide, a novel androgen receptor
antagonist, have been shown to improve the overall survival, and they are set to
be approved in Japan soon. Moreover, docetaxel and cabazitaxel have been
established as first- and second-line chemotherapeutic drugs, respectively.
Although there is currently no established molecular target drug for CRPC, some
drugs such as cabozantinib seem to be effective, and they may be used in the
future. In these situations of new drug development, the contribution of medical
oncologists is predictable. While medical oncologists cannot play central roles
in all aspects of drug therapy for urological malignancies in Japan, they must
play roles in certain aspects such as new drug development starting from phase I
trials, improving multidisciplinary care for adverse events, and promoting
translational research.
PMID- 25131869
TI - [Factors affecting adherence of breast cancer patients to adjuvant hormonal
therapy and validation of the evaluation method].
AB - BACKGROUND: The long-term use of hormonal therapy is important for the treatment
of patients with breast cancer. Therefore, we evaluated the methods used for
measuring adherence and examined factors that influence compliance. Our goal was
to improve overall adherence to the treatment. METHODS: Retrospective analyses by
using electronic medical records and questionnaires were performed on 294
patients with breast cancer. The patients were classified into 2 groups based on
the mean number of days when a dose was missed over a period of 28 days: group
A(range, 0-3 days, n=272)and group B (range, B4 days, n=22). Factors that may
influence adherence, including age, duration of hormonal therapy, the drug
administered in hormonal therapy, the surgical method, axillary lymph node
dissection, and adjuvant chemotherapy, were compared between both groups.
RESULTS: The adherence rates calculated from electronic medical records and
questionnaires were similar. The proportion of patients younger than 50 years was
30% in group A and 50% in group B(p<0.05). Additionally, there was a difference
in the duration of hormone therapy(752 days vs 981 days in groups A and B,
respectively; p< 0.05). Additional factors that are related to low-risk cancer
related procedures, such as breast conserving surgery, may also be linked to poor
adherence. CONCLUSION: Young age and long duration of hormonal therapy are
possibly related to poor adherence. Therefore, pharmacists should identify and
manage these patients to increase adherence.
PMID- 25131870
TI - [Efficacy and toxicity of pemetrexed monotherapy for previously untreated elderly
patients with non-squamous cell lung cancer with wild-type(or unknown)EGFR
status].
AB - BACKGROUND: The efficacy of docetaxel, vinorelbine, or gemcitabine monotherapy in
previously untreated elderly patients with non-small cell lung cancer has been
reported.Pemetrexed monotherapy has shown clinically equivalent efficacy to
docetaxel, a standard therapeutic option, in patients with previously treated non
small cell lung cancer and in those with a lower incidence of toxicity such as
febrile neutropenia. OBJECTIVE: In the present study, we aimed to investigate the
efficacy and toxicity of pemetrexed in previously untreated elderly patients with
non-squamous cell lung cancer and compare the results with those of docetaxel,
considered a standard chemotherapeutic agent. METHODS: We retrospectively
reviewed the medical records of patients with non-squamous cell lung cancer with
wild-type(or unknown)epidermal growth factor receptor status who received
pemetrexed or docetaxel monotherapy as first-line chemotherapy. RESULTS: We
analyzed 6 patients with lung adenocarcinoma in the pemetrexed group and 6
patients with lung adenocarcinoma in the docetaxel group. The median progression
free survival was 3.6 months for patients receiving pemetrexed and 3.1 months for
those receiving docetaxel(p=0.45). The median overall survival was 14.8 months in
the pemetrexed group and 10.9 months in the docetaxel group(p=0.36).Patients who
received docetaxel were more likely to have grade 3 or 4 neutropenia and febrile
neutropenia than those receiving pemetrexed.However, 2 patients who received
pemetrexed showed grade 3 pneumonitis. CONCLUSION: Pemetrexed monotherapy is a
promising treatment for previously untreated elderly patients with non-squamous
cell lung cancer.
PMID- 25131871
TI - [Value of the palliative prognostic index, controlling nutritional status, and
prognostic nutritional index for objective evaluation during transition from
chemotherapy to palliative care in cases of advanced or recurrent
gastrointestinal cancer].
AB - OBJECTIVE: We investigated whether objective evaluation by using the palliative
prognostic index(PPI), controlling nutritional status(COUNT), and prognostic
nutritional index(PNI)can provide prognostic information during the transition
from chemotherapy to palliative care in patients with advanced or recurrent
gastrointestinal cancer. METHODS: The subjects were 28 patients with
gastrointestinal cancer who died of their disease between January 2009 and June
2012. We compared the PPI, COUNT, and PNI scores between patients who died within
90 days of completing chemotherapy(Group A, n=14)and patients who survived for 90
or more days(Group B, n=14). RESULTS: The PPI score for Group A(4.0)was
significantly higher than that for Group B(0.8)(p<0.001). The COUNT score was
also significantly higher for Group A(6.3)than for Group B (3.9)(p=0.033). A
significant difference in survival was evident when the cutoff value for PNI was
set at 40 in the critical region(68/118, p=0.04). CONCLUSION: Our study suggests
that the PPI, COUNT, and PNI may be useful for objective evaluation during the
transition from chemotherapy to palliative care.
PMID- 25131872
TI - [The efficacy and safety of FOLFIRI or combined FOLFIRI and bevacizumab treatment
as second-line chemotherapy for metastatic colorectal cancer patients aged 75
years and older].
AB - The safety and efficacy of FOLFIRI as second-line chemotherapy for metastatic
colorectal cancer patients >= 75 years was retrospectively evaluated. We analyzed
106 patients, who received FOLFIRI or a combination of FOLFIRI and bevacizumab
following oxaliplatin-based first-line chemotherapy. The clinical characteristics
and outcome in elderly patients >=75 years(elderly[EP]group; n=18)were compared
with those in patients aged<75 years(control group; n=88). The number of patients
treated by a combination of FOLFIRI and bevacizumab in the EP group was lower
than that in the control group (27.8% vs 55.7%; p=0.03). The comparison revealed
no significant differences in response rate, progression-free survival, overall
survival, and the frequency of overall adverse events after the start of second
line chemotherapy, although the frequency of anemia(Bgrade 3, p=0.07)and
alopecia(grade 1/2, p=0.054)tended to be higher in the EP group than in the
control group. Although this study retrospectively analyzed a limited number of
patients, our results indicate that the safety and efficacy of FOLFIRI as second
line chemotherapy for metastatic colorectal cancer are almost equal in patients
>= 75 years and those aged<75 years.
PMID- 25131873
TI - [Opioid induction using rapid release drugs and the shift to fentanyl patches].
AB - SUBJECT AND METHODS: From April 2011 to March 2013, 20 patients with cancer pain
that was not controlled by non-opioid analgesics were treated with a short-acting
opioid for cancer pain management.The primary carcinoma sites were the stomach(
n=5), colo-rectum(n=5), lungs(n=3), urinary bladder(n=2), breast(n=2),
pancreas(n=2), and liver(n=1). The analgesic effects and adverse events were
evaluated, and a shift to fentanyl patches was made for patients whose cancer
pain was relieved.After the shift, the efficiency and safety were validated.
RESULTS: All 6 patients with a numeric rating scale (NRS)less than 5 at the time
of opioid induction had a good analgesic effect, and in only 1 patient, grade 2
constipation and grade 3 anorexia was observed.Of the 14 patients who had an NRS
of 6 or greater, 11 had a good analgesic effect.However, 3 patients experienced
no effect, and their survival periods after opioid induction were very short.In
the 11 patients with good pain control, only 3 patients exhibited grade 2 adverse
events.Nine patients out of 17 with a good analgesic effect caused by short
acting opioids were shifted to fentanyl patches, and 8 patients were under good
analgesic control for 2 weeks or more. CONCLUSION: Opioid induction using rapid
release drugs was effective and safe.However, these drugs should be clinically
considered at an early stage.Furthermore, in patients where a shift to a fentanyl
patch was possible, good long-term pain control was achieved.
PMID- 25131874
TI - [A case of mediastinal growing teratoma syndrome with acute megakaryoblastic
leukemia].
AB - We report a case of a 38-year-old man who was diagnosed with a mediastinal germ
cell tumor. After induction chemotherapy, the tumor marker levels normalized, but
the tumor itself continued to grow. Surgical resection was performed
successfully, but the patient developed acute megakaryoblastic leukemia 6 months
later, and induction and consolidation therapies failed to achieve remission.
Leukemia cells invaded the central nervous system following hematopoietic stem
cell transplantation, and the patient died 5 months after being diagnosed with
leukemia. This very rare case of a mediastinal germ cell tumor met the criteria
for "growing teratoma syndrome", against a background of acute megakaryoblastic
leukemia.
PMID- 25131875
TI - [Myelodysplastic syndrome with rapid disease progression after withdrawal of
treatment with azacitidine].
AB - A 73-year-old woman was diagnosed with myelodysplastic syndrome(MDS). After 11
courses of treatment with azacitidine( AZA), her hemoglobin level and platelet
count improved significantly, and she became transfusion independent. Therefore,
treatment was discontinued and follow-ups were maintained. Three months later,
her platelet count reduced again; we therefore treated her again with AZA.
However, MDS transformed to acute myeloid leukemia in the 14th course, and she
died 19 months after the initial diagnosis. AZA is an important drug for treating
MDS, but premature withdrawal of treatment might cause rapid disease progression.
In case treatment is discontinued, the patient needs to be carefully observed.
PMID- 25131876
TI - [Two cases of thymic carcinoid treated with octreotide long-acting repeatable].
AB - Thymic carcinoid is a rare disease that accounts for 3.1% of thymic tumors and
1.8-6% of all carcinoid tumors in Japan. Advanced thymic carcinoid has a 5-year
survival rate of 28-31%.Compared with carcinoid tumors that arise in other
organs, thyroid carcinoid tumors carry a relatively worse prognosis, and the most
effective therapeutic strategy is thought to be surgical resection.However, for
patients with recurrence and distant metastases, multimodal therapy including
radiotherapy and/or chemotherapy is usually applied.No chemotherapy treatment
regimen has been established in Japan, although the National Comprehensive Cancer
Network Guidelines proposed the application of octreotide long-acting
repeatable(LAR).In this report, we present two cases of thymic carcinoid that
were treated with octreotide LAR and achieved long-term survival.
PMID- 25131877
TI - [A case of gastric adenosquamous carcinoma with peritoneal dissemination in which
treatment with S-1 plus paclitaxel therapy resulted in improved long-term
survival].
AB - Gastric adenosquamous carcinoma is a rare malignancy with a poor prognosis. We
recently performed palliative gastrectomy for a gastric adenosquamous carcinoma
with peritoneal dissemination and provided a course of systemic chemotherapy with
S-1 plus paclitaxel(PTX)after the surgery. No serious adverse events were
observed, and treatment with S-1 plus PTX was continued for 1 year before being
switched to adjuvant chemotherapy with S-1 alone for another year. The tumor
maker levels normalized within 2 months of the initial treatment, and the
peritoneal dissemination could no longer be detected by abdominal computed
tomography(CT). The patient remained in clinical remission and maintained long
term survival of over 8 years.
PMID- 25131878
TI - [A patient with paclitaxel hypersensitivity treated with nab-paclitaxel].
AB - A 63-year-old man with multiple liver metastases from gastric cancer was treated
with S-1 plus cisplatin; however, the number of multiple liver metastases
increased. The patient received paclitaxel(PTX)treatment, but a hypersensitivity
reaction occurred after administering the second dose; therefore, he received
docetaxel treatment. A hypersensitivity reaction occurred after administering the
first dose of docetaxel; therefore, he received irinotecan treatment. However,
irinotecan administration was stopped because of severe diarrhea and weight
reduction. Subsequently, at the patient's request, nab-PTX treatment was
initiated by administering a premedication regimen of dexamethasone(8mg)and
chlorpheniramine(10mg); no hypersensitivity reactions were reported thereafter.
Nab-PTX is a contraindication; however, it might be possible to use nab-PTX for
treating patients with PTX hypersensitivity.
PMID- 25131879
TI - [A case of complete response to multiple liver metastasis of gastric cancer after
discontinuation of S-1 administration].
AB - An 80-year-old man was diagnosed with advanced gastric cancer and underwent
distal gastrectomy. Although the pathological Stage of the cancer was III A, he
refused adjuvant chemotherapy. One year later, CT revealed multiple liver
metastases. Therefore, he was started with S-1 administration and a complete
response was obtained at 10 months after starting S-1 administration. He has
maintained a complete response for 22 months after S-1 discontinuation.
PMID- 25131880
TI - [Successful treatment of advanced sigmoid colon cancer with liver metastases with
cetuximab monotherapy as first-line treatment-a case report].
AB - The prognosis for patients diagnosed with advanced colorectal cancer with liver
metastases is poor. Chemotherapy should be administered with caution in such
patients because of complications due to severe liver dysfunction. We report here
the successful management of a case of advanced sigmoid colon cancer, with
icterus due to severe liver metastases, treated with cetuximab as first-line
therapy. A 72-year-old man presented at our institution with complaints of severe
general fatigue, tarry stools, and abdominal distention. He was diagnosed with
advanced sigmoid colon cancer with multiple liver metastases. Clinical
examination revealed the presence of ascites. The patient had an Eastern
Cooperative Oncology Group(ECOG) performance status(PS)score of 3. A biopsy
specimen of the primary tumor showed well-moderately differentiated
adenocarcinoma without KRAS mutation. He was diagnosed with advanced sigmoid
colon cancer with multiple hepatic metastases. Cetuximab monotherapy was
initiated as first-line treatment. After 4 courses of cetuximab monotherapy,
results of laboratory tests showed an improvement, and a computed
tomography(CT)scan revealed a regression in the size of the liver metastases.
Because the results of liver function tests and the ECOG PS scores improved, we
initiated combination chemotherapy with 5-fluorouracil, Leucovorin,
oxaliplatin(FOLFOX), and cetuximab. This regimen was well tolerated up to 14
courses, during which the only adverse reaction reported was a rash of grade 2
toxicity. Thereafter, disease progression in the form of liver metastases
resulted in a change in the combination therapy to irinotecan and S-1(IRIS)as
second-line chemotherapy. Thereafter, irinotecan and panitumumab were
administered as third-line therapy. The patient continued chemotherapy on an
outpatient basis; however, he died due to disease progression 18 months after his
first visit.
PMID- 25131881
TI - [A case of post-operative recurrence of pancreatic cancer in the residual
pancreas treated by resection of the residual pancreas following radiological
complete response achieved with second-line FOLFIRINOX].
AB - A 65-year-old woman with carcinoma of the pancreatic body underwent Whipple's
operation. After surgery, adjuvant chemotherapy with gemcitabine alone, and S-1
combined with gemcitabine was conducted. But one year later, a recurrent tumor
was detected in the pancreatic tail. We administered FOLFIRINOX treatment for the
recurrent tumor. After 6 courses, FOLFIRINOX treatment resulted in a partial
response, and after 9 courses, a radiological complete response was achieved. We
could then perform total pancreatotectomy and resection of the metastatic liver
tumor. FOLFIRINOX as a second-line treat- ment was effective and safe in this
case. In cases of gemcitabine and/or S-1 failure, FOLFIRINOX treatment should be
considered.
PMID- 25131883
TI - [A case of esophageal squamous cell carcinoma with an adenocarcinoma component
that dedifferentiated after chemotherapy].
AB - CASE: A 69-year-old man was diagnosed with advanced esophageal cancer(well
differentiated squamous cell carcinoma). Neoadjuvant chemotherapy consisting of
nedaplatin and 5-fluorouracil(5-FU)was initiated. After two courses of
chemotherapy, the patient was judged to have achieved a clinical complete
response. The patient then decided against undergoing surgery and opted instead
to continue with the chemotherapy, receiving five courses in total. However, the
esophageal cancer recurred, and subtotal esophagectomy was performed in January
2011. Squamous cell carcinoma with an adenocarcinoma component, which consisted
of poorly differentiated squamous cell carcinoma and tubular adenocarcinoma
cells, was observed at the primary site. Metastasis of the cancer to the liver
was detected 2 months after surgery. The subsequent administration of four
courses of docetaxel to the patient did not result in any beneficial effects, and
the patient developed carcinomatous pleurisy and died of this complication in
November 2011. The patient survived for a total of 21 months after starting
chemotherapy. In this case, the chemotherapy itself may have resulted in the
dedifferentiation of a well differentiated squamous cell carcinoma to result in a
poorly differentiated squamous cell carcinoma with an adenocarcinoma component.
PMID- 25131882
TI - [A case of bleeding stomal varices during the course of oxaliplatin-based
chemotherapy for recurrent rectal cancer].
AB - A 51-year-old man with a history of an abdominoperineal resection of the rectum
and colostomy for rectal cancer underwent chemotherapy for multiple liver
metastases.Twenty -two courses of the folinic acid, 5-fluorouracil(5-FU)and
oxaliplatin(FOLFOX4)/bevacizumab(BEV)regimen and 39 courses of 5
FU/Leucovorin/BEV were administered.Progressive splenomegaly and stomal varices
were observed during the course of chemotherapy.The patient was admitted due to
excessive bleeding after colostomy.Angiography revealed bleeding stomal varices
secondary to portal hypertension.Splenectomy was performed with subsequent
reduction in the size of the stomal varices and no rebleeding was
observed.Oxaliplatin -based chemotherapy could lead to hepatic sinusoidal
dilation and induce splenomegaly and varix formation secondary to portal
hypertension.Our experience with this case suggests that careful attention should
be paid to stomal varices in colostomy patients receiving oxaliplatin-based
chemotherapy.
PMID- 25131884
TI - [A case of squamous cell carcinoma of the nipple skin successfully treated with S
1 alone].
AB - Squamous cell carcinoma of the breast is uncommon, but that of the nipple skin is
rarer. The effect of chemotherapy in these cases is yet to reach consensus. We
report a rare case in which primary squamous cell carcinoma of the nipple skin
was successfully treated with S-1 alone. A 64-year-old woman was admitted to our
hospital because of a granulomatous tumor mass over the right nipple, which she
was aware of for 10 years; the tumor showed a rapid increase in growth before
admission. The tumor was approximately 4 cm at the first visit, and was diagnosed
as squamous cell carcinoma by incisional biopsy. We administered preoperative
systemic chemotherapy owing to the presence of metastasis in an axillary lymph
node. After 2 courses of chemotherapy with oralS -1 at 100mg/day for 28 days
followed by a 14-day resting period, the primary tumor and metastatic lymph node
showed a remarkable reduction in size. The patient subsequently underwent a
radical operation and is currently healthy without any recurrence.
PMID- 25131886
TI - A cold-induced myo-inositol transporter-like gene confers tolerance to multiple
abiotic stresses in transgenic tobacco plants.
AB - A full length cDNA encoding a myo-inositol transporter-like protein, named as
MfINT-like, was cloned from Medicago sativa subsp. falcata (herein falcata), a
species with greater cold tolerance than alfalfa (M. sativa subsp. sativa). MfINT
like is located on plasma membranes. MfINT-like transcript was induced 2-4 h
after exogenous myo-inositol treatment, 24-96 h with cold, and 96 h by salinity.
Given that myo-inositol accumulates higher in falcata after 24 h of cold
treatment, myo-inositol is proposed to be involved in cold-induced expression of
MfINT-like. Higher levels of myo-inositol was observed in leaves of transgenic
tobacco plants overexpressing MfINT-like than the wild-type but not in the roots
of plants grown on myo-inositol containing medium, suggesting that transgenic
plants had higher myo-inositol transport activity than the wild-type. Transgenic
plants survived better to freezing temperature, and had lower ion leakage and
higher maximal photochemical efficiency of photosystem II (Fv /Fm ) after
chilling treatment. In addition, greater plant fresh weight was observed in
transgenic plants as compared with the wild-type when plants were grown under
drought or salinity stress. The results suggest that MfINT-like mediated
transport of myo-inositol is associated with plant tolerance to abiotic stresses.
PMID- 25131888
TI - A systematic review of the demoralization syndrome in individuals with
progressive disease and cancer: a decade of research.
AB - CONTEXT: Demoralization can be understood as a condition that results from
existential conflict. It presents with symptoms of hopelessness and helplessness
caused by a loss of purpose and meaning in life. It is a significant mental
health concern given there can be an associated desire for hastened death.
OBJECTIVES: The aim of this systematic review was to synthesize the recent
empirical evidence on demoralization in patients with progressive disease or
cancer, including prevalence rates; the relationships between demoralization and
sociodemographic, disease- and treatment-related, and psychological factors; and
the psychometric properties of demoralization measures. METHODS: A comprehensive
literature search using key words and subject headings was performed following
PRISMA guidelines with nine electronic bibliographic databases, resulting in 25
studies (33 articles) with a total of 4545 participants reviewed. Full articles
underwent methodological quality assessment, and correlational information was
synthesized according to the strength of evidence. RESULTS: The findings suggest
that demoralization is prevalent in patients with progressive disease or cancer
and clinically significant in 13%-18%. A range of factors were consistently
associated with demoralization: poorly controlled physical symptoms, inadequately
treated depression and anxiety, reduced social functioning, unemployment, and
single status. The Demoralization Scale has demonstrated good psychometric
properties across five studies. CONCLUSION: Overall, this systematic review was
limited by the extent of variability in the characteristics of studies. Patients
who are single, isolated or jobless, have poorly controlled physical symptoms, or
have inadequately treated anxiety and depressive disorders are at increased risk
for demoralization. Clinical recognition of demoralization can trigger more
focused interventions.
PMID- 25131887
TI - Limits and responsibilities of physicians addressing spiritual suffering in
terminally ill patients.
AB - CONTEXT: Many patients experience spiritual suffering that complicates their
physical suffering at the end of life. It remains unclear what physicians'
perceived responsibilities are for responding to patients' spiritual suffering.
OBJECTIVES: To investigate U.S. physician opinions about the impact patients'
unresolved spiritual struggles have on their physical pain, physicians'
responsibilities for treating patients' spiritual suffering compared with
patients' physical pain, and the number of patients in the past 12 months whose
suffering the physician was unable to relieve to an acceptable point. METHODS:
The study was based on a mailed survey to 2016 practicing U.S. physicians from
clinical specialties that care for significant numbers of dying patients.
RESULTS: Of 1878 eligible physicians, 1156 (62%) responded. Most physicians
agreed that patients with unresolved spiritual struggles tend to have worse
physical pain (81%) and that physicians should seek to relieve patients'
spiritual suffering just as much as patients' physical pain (88%). Compared with
physicians who strongly disagreed that physicians should seek to relieve
patients' spiritual suffering just as much as patients' physical pain, those who
strongly agreed were less likely to report being unable to relieve patients'
suffering to a point the physician found acceptable (27% vs. 54% reported three
or more such patients in the previous 12 months, adjusted odds ratio [95% CI] =
0.3 [0.1, 0.8]). CONCLUSION: Most physicians believe that spiritual suffering
tends to intensify physical pain and that physicians should seek to relieve such
suffering. Physicians who believe they should address spiritual suffering just as
much as physical pain report more success in relieving patient's suffering.
PMID- 25131889
TI - Screening for depression in advanced disease: psychometric properties,
sensitivity, and specificity of two items of the Palliative Care Outcome Scale
(POS).
AB - CONTEXT: Depression is common among patients with advanced disease but often
difficult to detect. OBJECTIVES: To assess the Palliative care Outcome Scale
(POS) (10 items) against the Geriatric Depression Scale (GDS)-10 total score and
the Hospital Anxiety and Depression Scale (HADS)-Depression subscale total score
and determine if the POS has appropriate items to screen for depression among
people with advanced disease. METHODS: This was a secondary analysis performed on
five studies. Four psychometric properties were assessed: data quality, scaling
assumptions, acceptability, and internal consistency (reliability). Receiver
operating characteristic (ROC) curves were used to determine the area under the
curve. Sensitivity, specificity, positive and negative predictive values, false
positive and negative rates, and positive and negative likelihood ratios were
computed. RESULTS: The overall sample had 416 patients from Germany and England:
144 had cancer and 267 had nonmalignant conditions. Prevalence of depression
across the sample was 17.5%. Floor and ceiling effects were rare. Cronbach's
alpha coefficients for POS items 7 and 8 summed, GDS-10 and HADS-Depression items
varied: 0.61 (heart failure) and 0.80 (cancer). Two items combined (Item 7
feeling depressed and Item 8-feeling good about yourself) consistently presented
the highest area under the ROC curve, ranging from 0.76 (95% CI 0.60, 0.93)
(Germany, lung cancer) to 0.97 (95% CI 0.91, 1.0) (heart failure), highest
negative predictive value, and lowest false negative rate. For the overall
sample, the cutoff 2/3 presented a negative predictive value of 89.4% (95% CI
84.7, 92.8) and false negative rate of 10.6 (95% CI 7.2, 15.3). CONCLUSION: POS
items 7 and 8 summed are potentially useful to screen for depression in advanced
disease populations.
PMID- 25131890
TI - Rapid resolution of refractory chemotherapy-induced oral mucositis with platelet
gel-released supernatant in a pediatric cancer patient: a case report.
PMID- 25131891
TI - Avoidable and unavoidable visits to the emergency department among patients with
advanced cancer receiving outpatient palliative care.
AB - CONTEXT: Admissions to the emergency department (ED) can be distressing to
patients with advanced cancer receiving palliative care. There is limited
research about the clinical characteristics of these patients and whether these
ED visits can be categorized as avoidable or unavoidable. OBJECTIVES: To
determine the frequency of potentially avoidable ED visits (AvEDs) for patients
with advanced cancer receiving outpatient palliative care in a large tertiary
cancer center, identify the clinical characteristics of the patients receiving
palliative care who visited the ED, and analyze the factors associated with AvEDs
and unavoidable ED visits (UnAvEDs). METHODS: We randomly selected 200 advanced
cancer patients receiving treatment in the outpatient palliative care clinic of a
tertiary cancer center who visited the ED between January 2010 and December 2011.
Visits were classified as AvED (if the problem could have been managed in the
outpatient clinic or by telephone) or UnAvED. RESULTS: Forty-six (23%) of 200 ED
visits were classified as AvED, and 154 (77%) of 200 ED visits were classified as
UnAvED. Pain (71/200, 36%) was the most common chief complaint in both groups.
Altered mental status, dyspnea, fever, and bleeding were present in the UnAvED
group only. Infection, neurologic events, and cancer-related dyspnea were
significantly more frequent in the UnAvED group, whereas constipation and running
out of pain medications were significantly more frequent in the AvED group (P <
0.001). In a multivariate analysis, AvED was associated with nonwhite ethnicity
(odds ratio [OR] 2.66; 95% CI 1.26, 5.59) and constipation (OR 17.08; 95% CI
3.76, 77.67), whereas UnAvED was associated with ED referral from the outpatient
oncology or palliative care clinic (OR 0.24; 95% CI 0.06, 0.88) and the presence
of baseline dyspnea (OR 0.46; 95% CI 0.21, 0.99). CONCLUSION: Nearly one-fourth
of ED visits by patients with advanced cancer receiving palliative care were
potentially avoidable. Proactive efforts to improve communication and support
between scheduled appointments are needed.
PMID- 25131892
TI - Doctors' decisions when faced with contradictory patient advance directives and
health care proxy opinion: a randomized vignette-based study.
AB - CONTEXT: Sometimes a written advance directive contradicts the opinion of a
health care proxy. How this affects doctors' decision making is unknown.
OBJECTIVES: To quantify the influence of contradictory instructions on doctors'
decisions. METHODS: All the generalists and internists in French-speaking
Switzerland were mailed the questionnaire. Respondents (43.5%) evaluated three
vignettes that described medical decisions for incapacitated patients. Each
vignette was produced in four versions: one with an advance directive, one with a
proxy opinion, one with both, and one with neither (control). In the first
vignette, the directive and proxy agreed on the recommendation to forgo a medical
intervention; in the second, the advance directive opposed, but the proxy favored
the intervention; and in the third, the roles were reversed. Each doctor received
one version of each vignette, attributed at random. The outcome variables were
the doctor's decision to forgo the medical intervention and the rating of the
decision as difficult. RESULTS: Written advance directives and proxy opinions
significantly influenced doctors' decision making. When both were available and
concordant, they reinforced each other (odds ratio [OR] of forgoing intervention
35.7, P < 0.001 compared with no instruction). When the directive and proxy
disagreed, the resulting effect was to forgo the intervention (ORs 2.1 and 2.2
for the two discordant vignettes, both P < 0.001). Discordance between
instructions was associated with increased odds of doctors rating the decision as
difficult (both ORs 2.0, P <= 0.001). CONCLUSION: Contradictions between advance
directives and proxy opinions result in a weak preference for abstention from
treatment and increase the difficulty of the decision.
PMID- 25131893
TI - Dying in the hospital: what happens and what matters, according to bereaved
relatives.
AB - CONTEXT: Most deaths in Western countries occur in hospital, but little is known
about factors determining the quality of dying (QOD). OBJECTIVES: The aim was to
assess the QOD in hospital as experienced by relatives and identify factors
related to QOD. METHODS: A cross-sectional study on 18 wards of a university
hospital in The Netherlands was conducted, including relatives of patients who
died after an admission of more than six hours, from June 2009 to March 2011.
Relatives' perceptions of QOD and quality of care and the relation between
dimensions of QOD and overall QOD scores were assessed. RESULTS: Two hundred
forty-nine relatives participated (51%) and rated overall QOD at 6.3 (SD 2.7;
range 0-10). According to relatives, patients suffered from 7.0 (SD 5.8) of 22
symptoms and were at peace with imminent death in 37%. Patients had been aware of
imminent death in 26%, and relatives were aware in 49%. Furthermore, 39% of
patients and 50% of relatives had said good-bye, and 77% of patients died in the
presence of a relative. Symptom alleviation was sufficient in 53%, and in 75%,
sufficient efforts had been made to relieve symptoms. Characteristics of QOD and
quality of care could be summarized in nine domains, explaining 34% of the
variation of QOD scores. Medical, personalized, and supportive care were most
strongly related to QOD. CONCLUSION: Relatives rated QOD as sufficient. A
majority of patients and relatives were not sufficiently prepared for imminent
death, and relatives experienced many problems. QOD appears to be a
multidimensional construct, strongly affected by medical care and staff
attentiveness.
PMID- 25131894
TI - Fipronil and imidacloprid reduce honeybee mitochondrial activity.
AB - Bees have a crucial role in pollination; therefore, it is important to determine
the causes of their recent decline. Fipronil and imidacloprid are insecticides
used worldwide to eliminate or control insect pests. Because they are broad
spectrum insecticides, they can also affect honeybees. Many researchers have
studied the lethal and sublethal effects of these and other insecticides on
honeybees, and some of these studies have demonstrated a correlation between the
insecticides and colony collapse disorder in bees. The authors investigated the
effects of fipronil and imidacloprid on the bioenergetic functioning of
mitochondria isolated from the heads and thoraces of Africanized honeybees.
Fipronil caused dose-dependent inhibition of adenosine 5'-diphosphate-stimulated
(state 3) respiration in mitochondria energized by either pyruvate or succinate,
albeit with different potentials, in thoracic mitochondria; inhibition was
strongest when respiring with complex I substrate. Fipronil affected adenosine 5'
triphosphate (ATP) production in a dose-dependent manner in both tissues and
substrates, though with different sensitivities. Imidacloprid also affected state
3 respiration in both the thorax and head, being more potent in head pyruvate
energized mitochondria; it also inhibited ATP production. Fipronil and
imidacloprid had no effect on mitochondrial state-4 respiration. The authors
concluded that fipronil and imidacloprid are inhibitors of mitochondrial
bioenergetics, resulting in depleted ATP. This action can explain the toxicity of
these compounds to honeybees.
PMID- 25131896
TI - Tactics for teaching evidence-based practice: improving self-efficacy in finding
and appraising evidence in a master's evidence-based practice unit.
AB - This column shares the best evidence-based strategies and innovative ideas on how
to facilitate the learning of EBP principles and processes by clinicians as well
as nursing and interprofessional students. Guidelines for submission are
available at http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1741-6787.
PMID- 25131897
TI - Cascade sensing of gold and thiols with imidazole-bearing functional porphyrins.
AB - An imidazole-bearing zinc porphyrin (PZn) has been designed for the selective
detection of Au(3+), and the porphyrin and gold complex (PZn.Au(3+)) can
additionally be used to identify gold-binding functional groups such as cysteine
residues and other mercaptans.
PMID- 25131898
TI - Assisted reproduction: Ethical and legal issues.
AB - Since inception, the use of assisted reproductive technologies (ART) has been
accompanied by ethical, legal, and societal controversies. Guidelines have been
developed to address many of these concerns; however, the rapid evolution of ART
requires their frequent re-evaluation. We review the literature on ethical and
legal aspects of ART, highlighting some of the most visible and challenging
topics. Of specific interest are: reporting of ART procedures and outcomes;
accessibility to ART procedures; issues related to fertility preservation,
preimplantation genetic testing, gamete and embryo donation, and reproductive
outcomes after embryo transfer. Improvements in ART reporting are needed
nationally and worldwide. Reporting should include outcomes that enable patients
to make informed decisions. Improving access to ART and optimizing long-term
reproductive outcomes, while taking into account the legal and ethical
consequences, are challenges that need to be addressed by the entire community of
individuals involved in ART with the assistance of bioethicists, legal
counselors, and members of society in general.
PMID- 25131899
TI - Geographical comparisons of information and support needs of Australian women
following the primary treatment of breast cancer: a 10-year replication study.
AB - BACKGROUND: In 2002, Raupach and Hiller examined the use of and satisfaction with
information and support following treatment of breast cancer from a sample of
participants in South Australia. In 2013 this study was replicated to include
participants Australia wide and analyse comparisons based on geographical
location. Statistical comparisons with the original study were also conducted.
DESIGN: A 10 year replication study using a cross-sectional needs analysis
survey. SETTING AND PARTICIPANTS: Women aged 18+ years diagnosed with breast
cancer between 6 and 30 months ago were sourced from two national databases of
women diagnosed with breast cancer. RESULTS: A total of 325 participants
completed the survey. The Internet was the most commonly used source of
information with 70% (n = 229 of 325) of women using the internet for
information, a statistically significantly higher percentage compared with the
2002 study. The study found the top four information issues rated as
moderately/extremely important by women in 2013 were identical in 2002. A
comparison of sources of support used showed that women in outer regional, remote
and very remote areas were statistically more likely to use the breast care nurse
(BCN) for support (P = 0.044). CONCLUSIONS: The study provides useful, up-to-date
data about information and support services used by Australian women with breast
cancer. Comparisons with the earlier study show some of the needs of women have
changed over time, but others have remained the same. Geographic comparisons
overall, demonstrate many consistent findings regardless of location, however,
the important work of the breast care nurse is an area in need of further
research.
PMID- 25131900
TI - Effects of salpingectomy and antituberculosis treatments on fertility results in
patients with genital tuberculosis.
AB - AIM: The aim of this study was to demonstrate the effects of tubal surgery and
antituberculosis treatments in patients with genital tuberculosis. MATERIAL AND
METHODS: A total of 38 infertile women who had been diagnosed with pelvic
tuberculosis and who had had laparoscopy and hysteroscopy were recruited into the
study. All women with female genital tuberculosis were divided into two groups:
group 1 (salpingectomized, n=21) and group 2 (not salpingectomized, n=15). Both
of the groups were treated with antitubercular therapy for 6-12 months. RESULTS:
There was no significant difference in level of gonadotrophins used, estradiol
levels on human chorionic gonadotrophin day, mean and mature oocytes retrieved,
mean embryos transferred, or cancellation and fertilization rates. Only the
number of days of stimulation was statistically significantly higher in group 1
compared to group 2 (10.4+/-2.3 vs 9.2+/-1.8; P=0.048). Although it did not reach
the statistically significant level, clinical pregnancy rate was higher in group
1 (37.5%, 12/32 vs 23.8%, 5/21; P=0.306). Although not statistically significant,
number of ongoing pregnancies per embryo transfer, spontaneous abortion rates
before 20 weeks of gestation and take-home baby rates were higher in group 1
compared to group 2 (15.5%, 12/77 vs 6.6%, 3/45; P=0.150; 28.1%, 9 vs 23.8%, 5;
P=0.600; 9%, 3 vs 0; P=0.160, respectively). CONCLUSION: Salpingectomy is an
option for treatment in patients diagnosed with pelvic tuberculosis and
infertility to improve both clinical pregnancy rates and take-home baby rates in
patients treated with antituberculosis therapy for 12 months.
PMID- 25131895
TI - The interferon regulatory factors as novel potential targets in the treatment of
cardiovascular diseases.
AB - The family of interferon regulatory factors (IRFs) consists of nine members (IRF1
IRF9) in mammals. They act as transcription factors for the interferons and thus
exert essential regulatory functions in the immune system and in oncogenesis.
Recent clinical and experimental studies have identified critically important
roles of the IRFs in cardiovascular diseases, arising from their participation in
divergent and overlapping molecular programmes beyond the immune response. Here
we review the current knowledge of the regulatory effects and mechanisms of IRFs
on the immune system. The role of IRFs and their potential molecular mechanisms
as novel stress sensors and mediators of cardiovascular diseases are highlighted.
PMID- 25131902
TI - Rhizosphere effect and salinity competing to shape microbial communities in
Phragmites australis (Cav.) Trin. ex-Steud.
AB - Rhizobacterial communities associated with Phragmites australis (Cav.) Trin. ex
Steud. in a hypersaline pond close to Wuliangsuhai Lake (Inner Mongolia - China)
were investigated and compared with the microbial communities in bulk sediments
of the same pond. Microbiological analyses have been done by automated ribosomal
intergenic spacer analysis (ARISA) and partial 16S rRNA gene 454 pyrosequencing.
Although community richness was higher in the rhizosphere samples than in bulk
sediments, the salinity seemed to be the major factor shaping the structure of
the microbial communities. Halanaerobiales was the most abundant taxon found in
all the different samples and Desulfosalsimonas was observed to be present more
in the rhizosphere rather than in bulk sediment.
PMID- 25131901
TI - Burden of epilepsy in rural Kenya measured in disability-adjusted life years.
AB - OBJECTIVES: The burden of epilepsy, in terms of both morbidity and mortality, is
likely to vary depending on the etiology (primary [genetic/unknown] vs. secondary
[structural/metabolic]) and with the use of antiepileptic drugs (AEDs). We
estimated the disability-adjusted life years (DALYs) and modeled the remission
rates of active convulsive epilepsy (ACE) using epidemiologic data collected over
the last decade in rural Kilifi, Kenya. METHODS: We used measures of prevalence,
incidence, and mortality to model the remission of epilepsy using disease
modeling software (DisMod II). DALYs were calculated as the sum of Years Lost to
Disability (YLD) and Years of Life Lost (YLL) due to premature death using the
prevalence approach, with disability weights (DWs) from the 2010 Global Burden of
Disease (GBD) study. DALYs were calculated with R statistical software with the
associated uncertainty intervals (UIs) computed by bootstrapping. RESULTS: A
total of 1,005 (95% UI 797-1,213) DALYs were lost to ACE, which is 433 (95% UI
393-469) DALYs lost per 100,000 people. Twenty-six percent (113/100,000/year, 95%
UI 106-117) of the DALYs were due to YLD and 74% (320/100,000/year, 95% UI 248
416) to YLL. Primary epilepsy accounted for fewer DALYs than secondary epilepsy
(98 vs. 334 DALYs per 100,000 people). Those taking AEDs contributed fewer DALYs
than those not taking AEDs (167 vs. 266 DALYs per 100,000 people). The proportion
of people with ACE in remission per year was estimated at 11.0% in males and
12.0% in females, with highest rates in the 0-5 year age group. SIGNIFICANCE: The
DALYs for ACE are high in rural Kenya, but less than the estimates of 2010 GBD
study. Three-fourths of DALYs resulted from secondary epilepsy. Use of AEDs was
associated with 40% reduction of DALYs. Improving adherence to AEDs may reduce
the burden of epilepsy in this area.
PMID- 25131903
TI - Appetite predicts mortality in free-living older adults in association with
dietary diversity. A NAHSIT cohort study.
AB - This study aimed to assess the predictive ability of appetite for mortality among
representative free-living Taiwanese older adults. A total of 1856 participants
aged 65 years or over from the Elderly Nutrition and Health Survey during 1999
2000 completed an appetite question in a larger questionnaire. Personal
information was obtained by face-to-face interview at baseline, together with a
24-hour dietary recall and simplified food frequency questionnaire which provided
a dietary diversity score and food intake frequency. Survivorship was ascertained
from the Death Registry until December 31, 2008. Participants with a poor
appetite had lower dietary diversity scores (DDS) and intake frequencies of meat,
fish and sea food, egg, vegetable and fruit intake, along with lower energy,
protein, vitamin B-1, niacin, iron and phosphate intakes. Those who had fair and
poor appetites had a higher risk of all-cause mortality compared to those with
good appetite, with hazard ratios (HR) (95% confidence interval, CI) of 1.28
(1.03-1.58) and 2.27 (1.71-3.02), respectively. After adjustment for confounders,
the HRs (95% CI) were 1.05 (0.83-1.33) and 1.50 (1.03-2.18), respectively. With
further adjustment for DDS or general health these HRs became non-significant.
The joint HR (95% CI) for "DDS <= 4 and poor appetite" was 1.77 (1.04-3.00)
compared to "DDS > 4 and good appetite" as referent. Poor appetite is associated
with lower food and nutrient intakes and an independent risk for mortality in
older Taiwanese. In conclusion, appetite is separate, mediated by general health
and modulated by dietary quality in its predictive capacity for mortality.
PMID- 25131904
TI - Relationship between mouthful volume and number of chews in young Japanese
females.
AB - OBJECTIVE: Modification of eating behavior in Japan is promoted to prevent
overweight and obesity, but the effects of such modifications are unclear. This
study aimed to clarify the inter- and intra-individual relationship between bite
size and number of chews of food. DESIGN AND METHODS: Subjects comprised of 50
young healthy Japanese women (mean age 19.5 years). Food materials were boiled
rice and apple. First, the average bite size and the number of chews per mouthful
of food were calculated across the study cohort. The number of chews was counted
by the subjects themselves and then self-reported. Correlation between the
individual one-bite volume and the number of chews per volume was analyzed using
Spearman's rank correlation coefficient. Second, the number of chews for three
different sized bites of food (half of one bite, one bite, and one-and-a-half
bites) were calculated as a prospective observational study. The number of chews
for each of the three volumes of food was compared using one way ANOVA with
Bonferroni correction. RESULTS: For both food types, there was a negative
correlation between individual mouthful volume and number of chews for both food
materials. The number of chews per volume decreased as bite sizes increased.
CONCLUSION: This study demonstrated an inter- and intra-individual relationship
between bite size and the number of chews and suggested that smaller bite sizes
were associated with more chews per volume of food.
PMID- 25131905
TI - Impact of clinical and echocardiographic characteristics on occurrence of cardiac
events in cardiac amyloidosis as proven by endomyocardial biopsy.
AB - BACKGROUND: Although patients with immunoglobulin light chain (AL) cardiac
amyloidosis exhibit worse outcomes than those with transthyretin (TTR) cardiac
amyloidosis, few data exist regarding the occurrence of cardiac events and the
echocardiographic indices in endomyocardial biopsy (EMBx) proven amyloidosis.
METHODS: From November 2007 to October 2012, we identified 33 patients with EMBx
proven amyloidosis. There were 12 patients (8 men; mean age: 66 years) with AL
and 21 patients (20 men; mean age: 78 years) with TTR. We performed serial
echocardiography and observed the patients during follow-up; defining all-cause
mortality as the primary endpoint and hospitalization for heart failure as the
secondary endpoint. RESULTS: The survival rates at 12 months were 20.8% and 85.7%
in AL and TTR, respectively (p<0.001). The cumulative incidences of the composite
of death or readmission for heart failure at 12 months were 91.7% and 51.3% in AL
and TTR, respectively (p<0.001). A multivariate analysis showed that the AL type
amyloid was the powerful predictor of mortality (hazard ratio: 8.50, 95%
confidence interval: 1.79 to 40.57, p<0.05). Under these conditions, the E/e' in
AL tended to increase from 23+/-13 to 28+/-11 (p=0.06) with marked increases in B
type natriuretic peptide (779+/-456 pg/ml to 1576+/-895 pg/ml, p<0.05), although
these remained unchanged in TTR, which exhibited significantly increased left
ventricular end-diastolic dimensions from 40+/-4 mm to 42+/-4 mm (p<0.05).
CONCLUSIONS: The survival rate was generally worse in AL cardiac amyloidosis,
although the readmission for heart failure remains high in TTR cardiac
amyloidosis with the occurrence of left ventricular dilatation.
PMID- 25131906
TI - A systematic review of clozapine induced cardiomyopathy.
AB - BACKGROUND: Clozapine is a unique anti-psychotic medication that is most
effective in the treatment of refractory schizophrenia and reducing suicidality.
Cardiomyopathy is among the side effects of this medication that limits its use.
There are a number of case reports, case series and expert opinion papers
discussing clozapine induced cardiomyopathy, but there is no evidence-based
review of the subject to guide clinicians. METHODS: We undertook a systematic
review of the literature on cardiomyopathy associated with clozapine. The primary
systemic search was in MEDLINE but EMBASE, PsycINFO, and Cochrane were searched
and manufacturers of clozapine were contacted for cases. Articles were then
individually reviewed to find additional reports. RESULTS: We identified 17
articles detailing 26 individual cases and 11 additional articles without
individual case data. The mean age at time of diagnosis was 33.5 years. The mean
dose of clozapine on presentation was 360 mg. Symptoms developed at an average of
14.4 months after initiating clozapine. The clinical presentation was generally
consistent with heart failure: including shortness of breath (60%) and
palpitations (36%). Echocardiography at presentation showed dilated
cardiomyopathy in 39% of cases and was not specified in other cases. CONCLUSION:
There should be a low threshold in performing echocardiography in suspected cases
of clozapine induced cardiomyopathy. Clozapine should be withheld in the setting
of cardiomyopathy without other explanation. There is limited data on the safety
of drug re-challenge in clozapine induced cardiomyopathy. Re-challenge may be
considered in carefully selected cases but close monitoring and frequent
echocardiography are required.
PMID- 25131907
TI - Response to the letter of Mynard and Smolich.
PMID- 25131908
TI - Retinal vessel analysis and heart rate variability.
PMID- 25131909
TI - Effectiveness of the combination therapy with lisinopril, ivabradine and
multivitamin supplementation in anthracycline-induced severe cardiotoxicity.
PMID- 25131910
TI - Hemoglobin and renal replacement therapy after cardiopulmonary bypass surgery: a
predictive score from the Cardiac Surgery Registry of Puglia.
AB - BACKGROUND: Acute Kidney Injury (AKI) after cardiac surgery is a complication
influencing postoperative outcome. Preoperative hemoglobin is a predictor of
postoperative AKI. We aimed to identify preoperative predictors of Renal
Replacement Therapy (RRT) and to develop a new risk-scoring system including
hemoglobin to better stratify the risk of events. METHODS: We evaluated 3288
consecutive patients of the Regional Cardiac Surgery Registry of Puglia operated
in 2011-2012. Chronic dialysis and renal transplantation patients were excluded.
Primary outcome was post-operative RRT incidence. RESULTS: The study sample was
divided in two cohorts: 1642 patients (70 RRT) operated during the year 2011 as
derivation cohort and 1646 patients (69 RRT) of the year 2012 as validation. In a
multivariable logistic regression model using a stepwise method, six preoperative
risk factors were associated with RRT in the derivation cohort: creatinine
clearance, preoperative hemoglobin, neurological dysfunction, left ventricular
ejection fraction, urgency and combined procedures (discrimination c-index 0.844
and 0.818 in the validation cohort). Scoring system included risk factors
obtained from derivation cohort adjusting their relative weight with updated
rounded coefficients in the validation cohort: creatinine clearance<50ml/min (1
point), hemoglobin<=12.5g/dl (1 point), left ventricular ejection fraction<=30%
(1 point), urgent operation (1 point), emergency-salvage surgery (2 points), and
combined procedures (1 point). In both cohorts, outcomes were strongly correlated
with score points. CONCLUSIONS: Our simple bedside prognostic score demonstrates
good performance in predicting RRT. Hemoglobin plays an important role and future
studies will clarify if preoperative anemia correction will lead to decreased RRT
risk.
PMID- 25131911
TI - Postconditioning or preconditioning, which should be promoted for protecting from
ischemic reperfusion injury? Response to letter IJC-D-14-02875.
PMID- 25131912
TI - ERBB1/EGFR and ERBB2 (HER2/neu)--targeted therapies in cancer and cardiovascular
system with cardiovascular drugs.
PMID- 25131913
TI - Detailed-comparison of average journal-impact-factors of oral and poster
abstracts presented at scientific-session that achieved publication at 2009
Radiological-Society of North-America Scientific-Assembly and Annual Meeting
including cardiac-session.
PMID- 25131914
TI - Lead extraction in a young girl with dehiscence of a pacemaker implanted in the
subpectoral region.
PMID- 25131915
TI - Assessment of the source of ischemic cerebrovascular events in patients with
Chagas disease.
PMID- 25131916
TI - Assessment of left coronary artery-to-left ventricle fistulae with left
ventricular non-compaction by multimodality imaging in a child.
PMID- 25131917
TI - Tacrolimus-induced left ventricular apical hypertrophy in a patient with post
allogeneic hematopoietic stem cell transplantation.
PMID- 25131918
TI - Inverse relationship between raft LRP1 localization and non-raft ERK1,2/MMP9
activation in idiopathic dilated cardiomyopathy: potential impact in ventricular
remodeling.
AB - BACKGROUND: Idiopathic dilated cardiomyopathy (IDCM) is characterized by adverse
ventricular remodeling attributed to altered activity of extracellular matrix
metalloproteinase (MMP). MMP overactivation is linked to changes in extracellular
signal-regulated kinases (ERK), reportedly modulated by the low-density
lipoprotein receptor-related protein 1 (LRP1) receptor. The aim of this work was
to compare the levels, membrane distribution and interactions of LRP1, ERK1,2 and
MMP2/9 in control and IDCM myocardium. METHODS: Left ventricle samples from IDCM
patients and control subjects were collected to analyze gene and protein
expression by Real-time PCR and Western blot, respectively. Fractions enriched in
cholesterol, Flotillin-1 and Caveolin-3 (rafts) were isolated from the remaining
membrane (non-rafts) by sucrose gradient ultracentrifugation. We assessed the
formation of LRP1-ERK1,2 complexes and MMP activity by immunoprecipitation and
zymography, respectively. RESULTS: In control myocardium, LRP1 was exclusively
found in non-rafts while activation of ERK1,2 was preferentially detected in
rafts. LRP1/p-ERK1,2 complexes were almost undetectable in rafts and non-rafts.
In contrast, in IDCM myocardium, LRP1 moved to rafts and ERK1,2 activation was
found in raft and non-raft fractions. Moreover, LRP1/p-ERK1,2 complexes were also
found in both membrane fractions, although the amount was higher in non-rafts
where MMP9 overactivation was exclusively detected. CONCLUSIONS: The presented
findings demonstrate a differential membrane compartmentalisation of ERK
signaling in IDCM myocardium. The movement of LRP1 to rafts and the concomitant
increase in non-raft-related ERK1,2/MMP9 activation may have crucial clinical
implications in the progression of disease.
PMID- 25131919
TI - Cardiovascular mortality in hypertensive patients newly prescribed perindopril
vs. lisinopril: a 5-year cohort study of 15,622 Chinese subjects.
AB - BACKGROUND: Perindopril and lisinopril are two common ACE inhibitors prescribed
for management of hypertension. Few studies have evaluated their comparative
effectiveness to reduce mortality. This study compared the all-cause and
cardiovascular related mortality among patients newly prescribed ACE inhibitors.
METHODS: All adult patients newly prescribed perindopril or lisinopril from 2001
to 2005 in all public clinics or hospitals in Hong Kong were retrospectively
evaluated, and followed up until 2010. Patients prescribed the ACE inhibitors for
less than a month were excluded. The all-cause mortality and cardiovascular
specific (i.e. coronary heart disease, heart failure and stroke) mortality were
compared. Cox proportional hazard regression model was used to assess the
mortality, controlling for age, sex, socioeconomic status, patient types, the
presence of comorbidities, and medication adherence as measured by the proportion
of days covered. An additional model using propensity scores was performed to
minimize indication bias. RESULTS: A total of 15,622 patients were included in
this study, in which 6910 were perindopril users and 8712 lisinopril users. The
all-cause mortality (22.2% vs. 20.0%, p<0.005) and cardiovascular mortality (6.5%
vs. 5.6%, p<0.005) were higher among lisinopril users than perindopril users.
From regression analyses, lisinopril users were 1.09-fold (95% C.I. 1.01-1.16)
and 1.18-fold (95% C.I. 1.02-1.35) more likely to die from any-cause and
cardiovascular diseases, respectively. Age-stratified analysis showed that this
significant difference was observed only among patients aged >70 years. The
additional models controlled for propensity scores yielded comparable results.
CONCLUSIONS: The long-term all-cause and cardiovascular related mortality rates
of lisinopril users was significantly different from those of perindopril users.
These findings showed that intra-class variation on mortality exists among ACE
inhibitors among those aged 70 years or older. Future studies should consider a
longer, large-scale randomized controlled trial to compare the effectiveness
between different medications in the ACEI class, especially among the elderly.
PMID- 25131921
TI - Cancer multidrug resistance-targeted therapy in both cancer and cardiovascular
system with cardiovascular drugs.
PMID- 25131920
TI - Three-dimensional aortic root reconstruction derived from rotational angiography
for transcatheter balloon-expandable aortic valve implantation guidance.
PMID- 25131922
TI - Inferior vena cava filters in the United States: less is more.
AB - Despite the widespread use of Inferior vena cava (IVC) filters, there is no
quality evidence to demonstrate their efficacy for routine use, nor there is a
consensus on their appropriate indications among major medical societies. The
introduction of retrievable filters led to further increase in the utilization of
these devices. However, several studies have shown that retrievable filters are
rarely retrieved. The implant rates of IVC filters are many folds higher in the
United States than in Europe, yet the retrieval rates are much lower. The U.S.
Food and Drug Administration has recently issued a safety alert advocating for
consideration of filter retrieval when the protection offered by the filter is no
longer needed. The controversies surrounding IVC filter placement and retrieval,
however, will likely to continue in the absence of good evidence on their
efficacy and side effects. Time has come for initiatives to conduct well designed
trials based on agreed-upon criteria to settle this debate.
PMID- 25131923
TI - PTX3: a modulator of human coronary plaque vulnerability acting by macrophages
type 2.
AB - BACKGROUND: Acute myocardial infarction (AMI), is related to a diffuse active
inflammation of the coronary tree associated with rupture of one of the multiple
vulnerable plaques. The presence of soluble mediators of inflammation with their
synergic or antagonistic actions coordinates the physiological response
determining the plaque fate and the fatal event. The present study focus on the
cytokines network operating in human coronary plaques of patients died from AMI
and controls, pointing out that coronaries of AMI patients produce PTX3 protein
twice as that of controls and express high level of PTX3 mRNA. RESULTS: The
presence of CX3CR1 polymorphisms is significantly correlated with the incidence
and the outcome of acute myocardial infarction inducing in the whole coronary
tree a strong recruitment of Th1 polarized inflammation that is directly
correlated to PTX3 expression. CONCLUSIONS: Moreover we found a positive
correlation between the expression of PTX3 in the plaque and the content of
macrophage cells showing a M2 polarization indicating the possible role of this
chemokine as mediator of immune response that would orchestrate plaque evolution
and inflammatory cell type activation.
PMID- 25131924
TI - MicroRNA-29b promotes high-fat diet-stimulated endothelial permeability and
apoptosis in apoE knock-out mice by down-regulating MT1 expression.
AB - BACKGROUND: High-fat diet has been reported to be associated with cardiovascular
diseases which is implicated in atherosclerosis. However, the underlying
mechanisms remain unknown. MicroRNAs (miRNAs) are non-coding small RNAs that
control gene expression at the post-transcriptional level. Dysregulated miRNAs
have been shown to be involved in atherosclerosis. METHODS AND RESULTS: This
study examined whether microRNA-29b (miR-29b) regulates high-fat diet induced
endothelial permeability and apoptosis by targeting MT1, a known melatonin
membrane receptor. In apoE knock-out mice, a high-fat diet increased miR-29b
expression and induced apoptosis as determined by up-regulation of caspase-3
activity. However, a standard diet did not alter apoptosis. miR-29b antagomir
decreased endothelial permeability and apoptosis in high-fat diet-stimulated
mice. In contrast, a miR-29b mimic enhanced endothelial permeability and
apoptosis. The induction of miR-29b correlated with a reduction in Bcl-2 and MT1
in high-fat diet-stimulated mice. miR-29b have an effect on the marker of
inflammation (NF-kappaB) and cell adhesion molecule (ICAM-1). We further showed
that miR-29b targeted and inhibited MT1 expression through a target site located
in the 3'un-translational region of MT1 mRNA. This study demonstrates a role of
miR-29b in atherosclerosis and identifies MT1 as a direct target of miR-29b.
CONCLUSIONS: The effect of miR-29b on endothelial permeability and apoptosis is
mediated through the down-regulation of MT1. Thus, miR-29b may be a new
therapeutic target for atherosclerosis.
PMID- 25131925
TI - Resource use and cost implications of implementing a heart failure program for
patients with systolic heart failure in Swedish primary health care.
AB - AIM: Heart failure (HF) is a common but serious condition which involves a
significant economic burden on the health care economy. The purpose of this study
was to evaluate cost and quality of life (QoL) implications of implementing a HF
management program (HFMP) in primary health care (PHC). METHODS AND RESULTS: This
was a prospective randomized open-label study including 160 patients with a
diagnosis of HF from five PHC centers in south-eastern Sweden. Patients
randomized to the intervention group received information about HF from HF nurses
and from a validated computer-based awareness program. HF nurses and physicians
followed the patients intensely in order to optimize HF treatment according to
current guidelines. The patients in the control group were followed by their
regular general practitioner (GP) and received standard treatment according to
local management routines. No significant changes were observed in NYHA class and
quality-adjusted life years (QALY), implying that functional class and QoL were
preserved. However, costs for hospital care (HC) and PHC were reduced by EUR
2167, or 33%. The total cost was EUR 4471 in the intervention group and EUR 6638
in the control group. CONCLUSIONS: Introducing HFMP in Swedish PHC in patients
with HF entails a significant reduction in resource utilization and costs, and
maintains QoL. Based on these results, a broader implementation of HFMP in PHC
may be recommended. However, results should be confirmed with extended follow-up
to verify long-term effects.
PMID- 25131926
TI - Superior vena cava obstruction as late complication of biventricular pacemaker
implantation: surgical replacement of the malfunctioning previous leads.
PMID- 25131927
TI - Assessment of coronary collateral artery by CT angiography in patients with ST
elevation acute myocardial infarction.
PMID- 25131928
TI - Severe autonomic failure as a predictor of mortality in aortic valve stenosis.
AB - BACKGROUND: Identification of new risk markers in aortic valve stenosis (AS) is
of great interest. Here, we hypothesized that the presence of severe autonomic
failure (SAF) is an important prognostic marker in both, symptomatic patients
undergoing invasive treatment for severe AS, and in asymptomatic patients with
severe AS who were primarily treated conservatively. METHODS: We prospectively
enrolled 300 patients with severe AS (aortic valve area<1.0 cm2 or mean aortic
gradient>40 mmHg) in sinus rhythm. All patients underwent a 24-h Holter recording
for assessment of heart rate turbulence (HRT) and deceleration capacity (DC).
Patients with both, abnormal DC and HRT were considered to suffer from SAF.
RESULTS: The first hypothesis was tested in 216 symptomatic patients who
underwent successful aortic valve replacement (AVR) or transcatheter aortic valve
implantation (TAVI). During follow-up of 2 years, 29 of these patients died. SAF
was the strongest independent predictor of mortality (hazard ratio 5.6, 95%
confidence interval 2.6-12.0; p<0.001) with 2-year mortality rates of 50.0% and
10.7% in SAF-positive and SAF-negative patients, respectively (p<0.001). The
second hypothesis was tested in 71 patients, who were asymptomatic at study entry
and for whom a primarily conservative treatment strategy was proposed. During
follow-up, 10 of these patients died. SAF also predicted death in asymptomatic
patients with 2-year mortality rates of 52.4% and 8.7% in SAF-positive and SAF
negative patients, respectively (p=0.010). CONCLUSIONS: SAF is a strong and
independent predictor of mortality in symptomatic and asymptomatic patients with
severe AS.
PMID- 25131929
TI - Localization of amyloid beta (Abeta1-42) protofibrils in membrane lateral
compartments: effect of cholesterol and 7-Ketocholesterol.
AB - Cholesterol plays an important role in the interaction of Alzheimer's amyloid
beta (Abeta) with cell membranes, an important event in Abeta-induced
cytotoxicity. However, it is not fully understood how cholesterol influences the
association of Abeta with membrane lateral compartments. We have shown that by
modulating membrane fluidity, cholesterol decreased peptide localization in solid
ordered domains and increased that in liquid-ordered domains. It changed the
amount of Abeta associating with liquid-disordered (Ld) phase with different
tendencies depending on the composition of heterogeneous membrane systems. 7
Ketocholesterol, an oxidized derivative of cholesterol, majorly enhanced the
fluidity of and Abeta interaction with Ld phase. These findings are useful for
clarifying the impact of cholesterol and its oxidation in Abeta-induced toxicity.
PMID- 25131931
TI - MiR-605 represses PSMD10/Gankyrin and inhibits intrahepatic cholangiocarcinoma
cell progression.
AB - The aberrant expression of PSMD10 has important functions in various
malignancies. This study showed that PSMD10 was highly expressed and inversely
correlated with the expression of miR-605 in intrahepatic cholangiocarcinoma
(ICC) specimens. MiR-605 directly targeted and repressed PSMD10 expression. In
addition, over-expression of miR-605 inhibited ICC cell progression both in vitro
and in vivo. This effect of miR-605 on ICC cells was similar to that of PSMD10
knock-down by RNAi. Moreover, restoration of PSMD10 could reverse the phenotypic
alteration caused by miR-605 in ICC cells. These results suggest a new
therapeutic strategy in ICC by restoring miR-605, which is regulated by p53.
PMID- 25131930
TI - Hepatitis C virus core protein enhances HIV-1 replication in human macrophages
through TLR2, JNK, and MEK1/2-dependent upregulation of TNF-alpha and IL-6.
AB - Despite their differential cell tropisms, HIV-1 and HCV dramatically influence
disease progression in coinfected patients. Macrophages are important target
cells of HIV-1. We hypothesized that secreted HCV core protein might modulate HIV
1 replication. We demonstrate that HCV core significantly enhances HIV-1
replication in human macrophages by upregulating TNF-alpha and IL-6 via TLR2-,
JNK-, and MEK1/2-dependent pathways. Furthermore, we show that TNF-alpha and IL-6
secreted from HCV core-treated macrophages reactivates monocytic U1 cells
latently infected with HIV-1. Our studies reveal a previously unrecognized role
of HCV core by enhancing HIV-1 infection in macrophages.
PMID- 25131932
TI - Paired related homeobox protein-like 1 (Prrxl1) controls its own expression by a
transcriptional autorepression mechanism.
AB - The homeodomain factor paired related homeobox protein-like 1 (Prrxl1) is crucial
for proper assembly of dorsal root ganglia (DRG)-dorsal spinal cord (SC) pain
sensing circuit. By performing chromatin immunoprecipitation with either
embryonic DRG or dorsal SC, we identified two evolutionarily conserved regions
(i.e. proximal promoter and intron 4) of Prrxl1 locus that show tissue-specific
binding of Prrxl1. Transcriptional assays confirm the identified regions can
mediate repression by Prrxl1, while gain-of-function studies in Prrxl1 expressing
ND7/23 cells indicate Prrxl1 can down-regulate its own expression. Altogether,
our results suggest that Prrxl1 uses distinct regulatory regions to repress its
own expression in DRG and dorsal SC.
PMID- 25131933
TI - A screen in mice uncovers repression of lipoprotein lipase by microRNA-29a as a
mechanism for lipid distribution away from the liver.
AB - Identification of microRNAs (miRNAs) that regulate lipid metabolism is important
to advance the understanding and treatment of some of the most common human
diseases. In the liver, a few key miRNAs have been reported that regulate lipid
metabolism, but since many genes contribute to hepatic lipid metabolism, we
hypothesized that other such miRNAs exist. To identify genes repressed by miRNAs
in mature hepatocytes in vivo, we injected adult mice carrying floxed Dicer1
alleles with an adenoassociated viral vector expressing Cre recombinase
specifically in hepatocytes. By inactivating Dicer in adult quiescent hepatocytes
we avoided the hepatocyte injury and regeneration observed in previous mouse
models of global miRNA deficiency in hepatocytes. Next, we combined gene and
miRNA expression profiling to identify candidate gene/miRNA interactions involved
in hepatic lipid metabolism and validated their function in vivo using antisense
oligonucleotides. A candidate gene that emerged from our screen was lipoprotein
lipase (Lpl), which encodes an enzyme that facilitates cellular uptake of lipids
from the circulation. Unlike in energy-dependent cells like myocytes, LPL is
normally repressed in adult hepatocytes. We identified miR-29a as the miRNA
responsible for repressing LPL in hepatocytes, and found that decreasing hepatic
miR-29a levels causes lipids to accumulate in mouse livers. CONCLUSION: Our
screen suggests several new miRNAs are regulators of hepatic lipid metabolism. We
show that one of these, miR-29a, contributes to physiological lipid distribution
away from the liver and protects hepatocytes from steatosis. Our results,
together with miR-29a's known antifibrotic effect, suggest miR-29a is a
therapeutic target in fatty liver disease.
PMID- 25131935
TI - In vitro combined treatment with cetuximab and trastuzumab inhibits growth of
colon cancer cells.
AB - OBJECTIVES: Overexpression or constitutive activation of epidermal growth factor
receptors (EGFR) is involved in growth of human cancers. We investigated effects
of EGFR and HER-2 blockade in colon cancer cell lines using cetuximab and
trastuzumab, with the aim of developing novel approaches to cancer therapy.
MATERIALS AND METHODS: We studied effects of treatment on cell growth, cell cycle
distribution, induction of apoptosis, changes in EGFR and HER-2 mRNA-protein
expression and EGFR and HER-2 gene copy number in Caco-2, HT-29 and HCT-116
cells. RESULTS: Treatment of cells resulted in no effect in one of the three cell
lines and in inhibition of cell proliferation in a time- and dose-dependent
manner in the other two, with modulation of EGFR and HER-2 mRNA and protein
levels. Differences in sensitivity to cetuximab and trastuzumab were observed.
Treatment induced specific changes in cell cycle distribution in both cell lines
affected, while apoptosis was not increased. Fluorescence in situ hybridization
analysis revealed abnormal copy number of two genes resulting from aneuploidy;
this was not responsible for different sensitivity to combination between the two
cell lines. CONCLUSIONS: Targeting EGFR and HER-2 simultaneously could have
useful applications in colorectal cancer treatment. To improve pharmacological
efficacy of cetuximab and trastuzumab combination, molecular mechanisms involved
in their activity need to be elucidated.
PMID- 25131937
TI - Protective effect of the herbal preparation, STW 5, against intestinal damage
induced by gamma radiation in rats.
AB - PURPOSE: STW 5 (marketed as Iberogast((r)), Steigerwald Arzneimittelwerk GmbH,
Darmstadt, Germany) is a herbal preparation reported to possess anti-inflammatory
properties and antioxidant activity. We investigated the effect of STW 5 against
intestinal injury induced after whole body exposure to ionizing radiation (IR).
MATERIALS AND METHODS: Intestinal mucositis was induced in rats by irradiation at
a level of 6 Gy. STW 5 (5 ml/kg) was delivered orally for 5 days before
irradiation and 2 days after. Rats were sacrificed, jejunum homogenates were
tested to assess biochemical parameters indicating intestinal injury and jejunum
segments were exposed to semi-quantitative histological examination. RESULTS: IR
led to an increase in overall damage severity (ODS) score associated with a
significant rise in tumor necrosis factor (TNF-alpha) and thiobarbituric acid
reactive substances (TBARS) by 46% and 50% (p <= 0.05), respectively, whereas the
reduced glutathione (GSH), sucrase and alkaline phosphatase enzyme activities
were significantly decreased by 68%, 76% and 25% (p <= 0.05), respectively, in
intestinal homogenates. IR led to a reduction of plasma citrulline. Pre-treatment
with STW 5 guarded against the changes in ODS score and in all parameters
measured. CONCLUSION: Pre-treatment with STW 5 has the potential to decrease the
severity of radiation-induced mucositis.
PMID- 25131934
TI - Transplantation of mesenchymal stem cells into the renal medulla attenuated salt
sensitive hypertension in Dahl S rat.
AB - Adult stem cell deficiency has been implicated in the pathogenic mechanism for
various diseases. Renal medullary dysfunction is one of the major mechanisms for
the development of hypertension in Dahl salt-sensitive (S) rats. The present
study first detected a stem cell deficiency in the renal medulla in Dahl S rats
and then tested the hypothesis that transplantation of mesenchymal stem cells
(MSCs) into the renal medulla improves salt-sensitive hypertension in Dahl S
rats. Immunohistochemistry and flowcytometry analyses showed a significantly
reduced number of stem cell marker CD133+ cells in the renal medulla from Dahl S
rats compared with controls, suggesting a stem cell deficiency. Rat MSCs or
control cells were transplanted into the renal medulla in uninephrectomized Dahl
S rats, which were then treated with a low- or high-salt diet for 20 days. High
salt-induced sodium retention and hypertension was significantly attenuated in
MSC-treated rats compared with control cell-treated rats. Meanwhile, high-salt
induced increases of proinflammatory factors, monocyte chemoattractant protein-1,
and interleukin-1beta, in the renal medulla were blocked by MSC treatment.
Furthermore, immunostaining showed that high-salt-induced immune cell
infiltration into the renal medulla was substantially inhibited by MSC treatment.
These results suggested that stem cell defect in the renal medulla may contribute
to the hypertension in Dahl S rats and that correction of this stem cell defect
by MSCs attenuated hypertension in Dahl S rats through anti-inflammation. KEY
MESSAGE: Stem cell defect in the renal medulla may contribute to salt-sensitive
hypertension Stem cell therapy is a potential therapeutic strategy for salt
sensitive hypertension Normal stem cell inhibits the inflammatory response to
high salt in the renal medulla.
PMID- 25131938
TI - Understanding key influencers' attitudes and beliefs about healthy public policy
change for obesity prevention.
AB - OBJECTIVE: As overweight and obesity is a risk factor for chronic diseases, the
development of environmental and healthy public policy interventions across
multiple sectors has been identified as a key strategy to address this issue.
METHODS: In 2009, a survey was developed to assess the attitudes and beliefs
regarding health promotion principles, and the priority and acceptability of
policy actions to prevent obesity and chronic diseases, among key policy
influencers in Alberta and Manitoba, Canada. Surveys were mailed to 1,765 key
influencers from five settings: provincial government, municipal government,
school boards, print media companies, and workplaces with greater than 500
employees. A total of 236 surveys were completed with a response rate of 15.0%.
RESULTS: Findings indicate nearly unanimous influencer support for individual
focused policy approaches and high support for some environmental policies.
Restrictive environmental and economic policies received weakest support. Obesity
was comparable to smoking with respect to perceptions as a societal
responsibility versus a personal responsibility, boding well for the potential of
environmental policy interventions for obesity prevention. CONCLUSIONS: This
level of influencer support provides a platform for more evidence to be brokered
to policy influencers about the effectiveness of environmental policy approaches
to obesity prevention.
PMID- 25131940
TI - DFT investigation of the mechanism of E/Z isomerization of nitrones.
AB - The hitherto unknown mechanism of E/Z isomerization of nitrones, with important
implications in 1,3-dipolar cycloaddition chemistry, has been investigated using
density functional theory calculations. Unimolecular and bimolecular processes
have also been considered. Both concerted and stepwise mechanisms involving
either zwitterionic or diradical species have been studied. The unimolecular
torsional mechanism and isomerization through intermediate oxaziridines present
energy barriers too high to justify the observed experimental results. Several
bimolecular processes involving an initial dimerization are possible. Among them,
the concerted process can be discarded in terms of energy barrier. Zwitterionic
intermediates are too high in energy to be considered. From the two possible
diradical approaches consisting of either C-O or C-C coupling, the latter is the
most favored. Thus, the mechanism of E/Z isomerization of nitrones proceeds via a
diradical bimolecular process involving an initial dimerization through a C-C
coupling followed by a dedimerization, with energy barriers for the rate-limiting
step of 29.9 kcal/mol for C-methyl nitrones and 25.8 kcal/mol for C
(methoxycarbonyl) nitrones. These values are in very good agreement with the
experimental data previously measured through kinetic experiments.
PMID- 25131939
TI - The implementation of a protocol promoting the safe practice of brain death
determination.
AB - PURPOSE: The purpose of the study is to describe the implementation of measures
introduced in Israel in 2009 to promote the safe practice of brain death
determination (BDD). MATERIALS AND METHODS: The measures require (1) physicians
to undergo a mandatory training course, (2) the mandatory performance of an
ancillary test, and (3) retrospective examination of all BDD forms by an
independent committee. Any deviations from practice parameters were noted.
Surveys were also undertaken to assess (i) the attitude of local physicians to
the measures and (ii) whether similar measures are in place in Europe and whether
they were considered necessary. RESULTS: After implementation, the measures
resulted in the absence of deviations from practice parameters over time. A
majority of local physician (n = 64) felt the measures added a sense of security
to BDD (73%) and ensured its proper performance (85%). The European survey (n =
20 countries) revealed (1) specialized BDD training is required in 60%, provided
in 50%, while felt necessary by 80%; (2) independent supervision of BDD is
performed in only one other country; and (3) BDD is performed country-wide using
the same criteria in 80% while felt necessary by 95%. CONCLUSION: The measures
were successfully implemented, reduced diversity in patient testing, and
positively accepted by local physicians. Wider application of the measures may be
appropriate as suggested by the results of a European survey and the variability
of BDD reported in the literature.
PMID- 25131941
TI - High prevalence of early hypothalamic-pituitary damage in childhood brain tumor
survivors: need for standardized follow-up programs.
AB - INTRODUCTION: Childhood brain tumor survivors (CBTS) are at increased risk to
develop endocrine disorders. Alerted by two cases who experienced delay in
diagnosis of endocrine deficiencies within the first 5 years after brain tumor
diagnosis, our aim was to investigate the current screening strategy and the
prevalence of endocrine disorders in survivors of a childhood brain tumor outside
of the hypothalamic-pituitary region, within the first 5 years after diagnosis.
PROCEDURES: Firstly, we performed a retrospective study of 47 CBTS treated in our
center, diagnosed between 2008 and 2012. Secondly, the literature was reviewed
for the prevalence of endocrine disorders in CBTS within the first 5 years after
diagnosis. RESULTS: Of 47 CBTS eligible for evaluation, in 34% no endocrine
parameters had been documented at all during follow up. In the other 66%,
endocrine parameters had been inconsistently checked, with different parameters
at different time intervals. In 19% of patients an endocrine disorder was found.
At literature review 22 studies were identified. The most common reported
endocrine disorder within the first 5 years after diagnosis was growth hormone
deficiency (13-100%), followed by primary gonadal dysfunction (0-91%) central
hypothyroidism (0-67%) and primary/subclinical hypothyroidism (range 0-64%).
CONCLUSION: Endocrine disorders are frequently seen within the first 5 years
after diagnosis of a childhood brain tumor outside of the hypothalamic-pituitary
region. Inconsistent endocrine follow up leads to unnecessary delay in diagnosis
and treatment. Endocrine care for this specific population should be improved and
standardized. Therefore, high-quality studies and evidence based guidelines are
warranted.
PMID- 25131942
TI - Foetal exposure to maternal depression predicts cortisol responses in infants:
findings from rural South India.
AB - BACKGROUND: Maternal depression during pregnancy is associated with an increased
risk of adverse child outcomes. One potential mechanism is the influence of
antenatal depression on the foetal hypothalamic-pituitary-adrenal axis. This can
be observed as disturbances in baseline cortisol secretion during childhood. The
influence of antenatal depression on infant cortisol reactivity to a stressor may
provide further insight into this association. In addition, the dose-response
relationship between foetal exposure to antenatal depression and infant cortisol
reactivity is unclear. METHODS: A consecutive sample of 133 pregnant women in
their third trimester was recruited from an antenatal clinic in Karnataka, South
India. Women were assessed for depression before and after birth on the Edinburgh
Postnatal Depression Scale (EPDS) and the Kessler 10 Scale. Salivary cortisol
response to immunization was measured in 58 infants at 2 months of age. We aimed
(i) to investigate the association between antenatal depression and infant
cortisol reactivity to immunization and (ii) to explore whether the relationship
is dose-dependent. RESULTS: Exposure to antenatal depression independently
predicted elevated infant cortisol responses to immunization (beta = 0.53, P =
0.04). The association was found to be U-shaped, for antenatal depression
measured on the EPDS, with the infants exposed to the highest and lowest levels
of maternal antenatal EPDS scores during intra-uterine life showing elevated
cortisol responses to immunization (R(2) = 0.20, P = 0.02). Infants exposed to
moderate levels of maternal antenatal depression showed the lowest cortisol
response to immunization. CONCLUSIONS: These findings suggest that the
association between antenatal depression and infant cortisol reactivity is dose
dependent and U-shaped, implying that infants exposed to both low and high levels
of maternal depression showed greater reactivity. The study provides the first
evidence of such an association from a low-income setting.
PMID- 25131944
TI - Clinical Neuropathology image 5-2014: alpha-synuclein pathology in the ependyma
in Parkinson's disease.
PMID- 25131945
TI - Detection of disease-associated alpha-synuclein in the cerebrospinal fluid: a
feasibility study.
AB - With the aim to evaluate the significance and reliability of detecting disease
specific alpha-synuclein in the cerebrospinal fluid (CSF) we developed an ELISA
and bead-assay. We used a commercial antibody (5G4) that does not bind to the
physiological monomeric form of alpha-synuclein, but is highly specific for the
disease-associated forms, including high molecular weight fraction of beta-sheet
rich oligomers. We applied both tests in CSF from a series of neuropathologically
confirmed alpha-synucleinopathy cases, including Parkinson' disease dementia
(PDD) and dementia with Lewy bodies (DLB) (n = 7), as well as Alzheimer' disease
(n = 6), and control patients without neurodegenerative pathologies (n = 9).
Disease-specific alpha-synuclein was detectable in the CSF in a subset of
patients with alpha-synuclein pathology in the brain. When combined with the
analysis of total alpha-synuclein, the bead-assay for disease-specific alpha
synuclein was highly specific for PDD/DLB. Detection of disease-associated
alphasynuclein combined with the total levels of alpha-synuclein is a promising
tool for the in-vivo diagnosis of alpha-synucleinopathies, including PDD and LBD.
PMID- 25131946
TI - Advances in the development of novel antioxidant therapies as an approach for
fetal alcohol syndrome prevention.
AB - Ethanol is the most common human teratogen, and its consumption during pregnancy
can produce a wide range of abnormalities in infants known as fetal alcohol
spectrum disorder (FASD). The major characteristics of FASD can be divided into:
(i) growth retardation, (ii) craniofacial abnormalities, and (iii) central
nervous system (CNS) dysfunction. FASD is the most common cause of nongenetic
mental retardation in Western countries. Although the underlying molecular
mechanisms of ethanol neurotoxicity are not completely determined, the induction
of oxidative stress is believed to be one central process linked to the
development of the disease. Currently, there is no known effective strategy for
prevention (other than alcohol avoidance) or treatment. In the present review we
will provide the state of art in the evidence for the use of antioxidants as a
potential therapeutic strategy for the treatment using whole-embryo and culture
cells models of FASD. We conclude that the imbalance of the intracellular redox
state contributes to the pathogenesis observed in FASD models, and we suggest
that antioxidant therapy can be considered a new efficient strategy to mitigate
the effects of prenatal ethanol exposure.
PMID- 25131947
TI - Different HBsAg decline after 3 years of therapy with entecavir in patients
affected by chronic hepatitis B HBeAg-negative and genotype A, D and E.
AB - The role of measurement of hepatitis B "s" antigen (HBsAg) during the therapy
with oral nucleos(t)ide analogues is still debatable. The HBsAg declines after 3
years of therapy with entecavir (ETV) was investigated among patients affected by
hepatitis B virus (HBV), e antigen (HBeAg)-negative and genotypes A, D and E. A
prospective cohort of 123 patients was enrolled consecutively from April 2007 to
May 2010 with at least 3 years of treatment with ETV. Patients with chronic HBV
infection, HBeAg-negative, naive for previous treatment and with virological
response to ETV were included in the study. HBsAg level and HBV-DNA were tested
every 3 months during the first year of treatment, then every 6 months for a time
of at least 3 years. After 3 years, HBsAg decline was 0.77 log IU/ml, 0.65 log
IU/ml, 0.45 respectively; A versus D (P = 0.012), A versus E (P < 0.001), D
versus E (P < 0.001). In the multivariate linear regression analysis only the HBV
genotype was predictive of HBsAg decline after 3 years of treatment (P < 0.001).
The expected time to HBsAg loss was 15.6 years for the A genotype, 17 years for
D, 24.6 years for E (P < 0.001). The treatment with ETV leads the different
kinetics in HBsAg decline among genotypes A, D and E; the expected time of HBsAg
loss was significantly higher in E genotype compared to A and D genotype.
PMID- 25131948
TI - Transcript elongation factors: shaping transcriptomes after transcript
initiation.
AB - Elongation is a dynamic and highly regulated step of eukaryotic gene
transcription. A variety of transcript elongation factors (TEFs), including
modulators of RNA polymerase II (RNAPII) activity, histone chaperones, and
histone modifiers, have been characterized from plants. These factors control the
efficiency of transcript elongation of subsets of genes in the chromatin context
and thus contribute to tuning gene expression programs. We review here how
genetic and biochemical analyses, primarily in Arabidopsis thaliana, have
advanced our understanding of how TEFs adjust plant gene transcription. These
studies have revealed that TEFs regulate plant growth and development by
modulating diverse processes including hormone signaling, circadian clock,
pathogen defense, responses to light, and developmental transitions.
PMID- 25131949
TI - Imatinib mesylate plus hydroxyurea chemotherapy for cerebellar meningioma in a
Belgian Malinois dog.
AB - An 8-year-old intact male Belgian Malinois, weighing 37.2 kg, was referred for
evaluation due to right side facial paresis, ataxia and a 2-month history of
decreased cognitive ability. Physical and neurological examinations revealed mild
depression, left-sided head tilt, right-sided facial paresis and ataxia. A well
demarcated, broad-based cerebellar mass and hyperostosis were found on CT imaging
of the brain. Based on these CT findings, a cerebellar meningioma was strongly
suspected. Hydroxyurea and prednisolone were administered; after 4 weeks, there
was reduction in mass size as compared to initial CT results. However, the mass
size was found to have grown 6 weeks after hydroxyurea treatment. We then
prescribed a combination of imatinib mesylate and hydroxyurea. Two weeks
following combination treatment, the mass size had reduced significantly. The
mass continuously decreased in size until the patient died during anesthesia.
Cerebellar transitional meningioma was confirmed by histopathologic examination.
To the author's knowledge, this is the first reported case of imatinib mesylate
plus hydroxyurea therapy for the treatment of meningioma in veterinary medicine.
PMID- 25131950
TI - Profiling of serum metabolites in canine lymphoma using gas chromatography mass
spectrometry.
AB - Canine lymphoma is a common cancer that has high rates of complete remission with
combination chemotherapy. However, the duration of remission varies based on
multiple factors, and there is a need to develop a method for early detection of
recurrence. In this study, we compared the metabolites profiles in serum from 21
dogs with lymphoma and 13 healthy dogs using gas chromatography mass spectrometry
(GC-MS). The lymphoma group was separated from the control group in an orthogonal
projection to latent structure with discriminant analysis (OPLS-DA) plot using
ions of m/z 100-600, indicating that the metabolites profiles in lymphoma cases
differed from those in healthy dogs. The lymphoma group was also separated from
the control group on OPLS-DA plot using 29 metabolites identified in all serum
samples. Significant differences were found for 16 of these metabolites with
higher levels in the lymphoma group for 15 of the metabolites and lower levels
for inositol. An OPLS-DA plot showed separation of the lymphoma and healthy
groups using these 16 metabolites only. These results indicate that metabolites
profile with GC-MS may be a useful tool for detection of potential biomarker and
diagnosis of canine lymphoma.
PMID- 25131951
TI - Internet searches and allergy: temporal variation in regional pollen counts
correlates with Google searches for pollen allergy related terms.
PMID- 25131952
TI - Are the fabellae bisected by the femoral cortices in a true craniocaudal pelvic
limb radiograph?
AB - OBJECTIVES: To assess whether the bisection of the fabellae by their respective
femoral cortices is a useful criterion for assessing positioning of craniocaudal
pelvic limb radiographs, and whether this is consistent in limbs affected or
unaffected by medial patella luxation. METHODS: Computed tomography multi-planar
reconstructions were used to determine the relative positions of the fabellae
with respect to the femoral cortices. RESULTS: Only 36% of fabellae overall were
bisected by the femoral cortex. There was no significant difference between limbs
affected or unaffected by medial patella luxation. CLINICAL SIGNIFICANCE: The
accurate measurement of femoral varus angle is important in pre-surgical planning
of distal femoral ostectomy. Radiography is normally used to obtain the femoral
varus angle, and femoral rotational malpositioning will induce errors in the
femoral varus angle measured. Bisection of the fabellae by the femoral cortices
is commonly cited as a criterion by which to assess whether a radiographic
projection is truly craniocaudal, yet this study has shown this not to be valid.
PMID- 25131954
TI - Reduction of the scanning time by total variation minimization reconstruction for
X-ray tomography in a SEM.
AB - Total variation minimization is applied to the particular case of X-ray
tomography in a scanning electron microscope. To prove the efficiency of this
reconstruction method, noise-free and noisy data based on the Shepp & Logan
phantom have been simulated. These simulations confirm that Total variation
minimization-reconstruction algorithm better manages data containing low number
of projections with respect to simultaneous iterative reconstruction technique or
filtered backprojection, even in the presence of noise. The algorithm has been
applied to real data sets, with a low angular sampling and a high level of noise.
Two samples containing micro-interconnections have been analyzed and 3D
reconstructions show that Total variation minimization-based algorithm performs
well even with 60 projections in order to properly recover a 500 nm diameter void
inside a copper interconnection.
PMID- 25131953
TI - Conformational and aggregation properties of the 1-93 fragment of apolipoprotein
A-I.
AB - Several disease-linked mutations of apolipoprotein A-I, the major protein in high
density lipoprotein (HDL), are known to be amyloidogenic, and the fibrils often
contain N-terminal fragments of the protein. Here, we present a combined
computational and experimental study of the fibril-associated disordered 1-93
fragment of this protein, in wild-type and mutated (G26R, S36A, K40L, W50R)
forms. In atomic-level Monte Carlo simulations of the free monomer, validated by
circular dichroism spectroscopy, we observe changes in the position-dependent
beta-strand probability induced by mutations. We find that these conformational
shifts match well with the effects of these mutations in thioflavin T
fluorescence and transmission electron microscopy experiments. Together, our
results point to molecular mechanisms that may have a key role in disease-linked
aggregation of apolipoprotein A-I.
PMID- 25131955
TI - Antimicrobial susceptibility and molecular characterization of Mycobacterium
intracellulare in China.
AB - Mycobacterium avium complex (MAC) is the most common non-tuberculosis
mycobacterial pathogen isolated from respiratory samples, mainly including two
species, Mycobacterium avium (M. avium) and Mycobacterium intracellulare (M.
intracellulare). Although these two species belong to the same group, M. avium
and M. intracellulare reveal significantly differences in pathogenicity and
biology. Nevertheless, little is known regarding the drug resistant details
profile of M. avium or M. intracellulare instead of MAC. Here, we examined the
antimicrobial susceptibility profiles of 52 clinical M. intracellulare isolates
against fourteen antimicrobial agents, which are widely selected for the
treatment of nontuberculous mycobacteria (NTM) infection. The drug susceptibility
test revealed that clarithromycin (47/52, 90.4%), rifampicin (41/52, 78.8%) and
capreomycin (40/52, 76.9%) revealed highly antimicrobial activities against M.
intracellulare isolates in vitro. Furthermore, all clarithromycin resistant
isolates harbored mutations in the 23S rRNA gene, and the percentage of amikacin
resistant ones with mutation in the rrs gene is 62.5% (10/16). The Hunter-Gaston
Discriminatory Index (HGDI) value for the 16-loci Variable Number of Tandem
Repeat (VNTR) typing of M. intracellulare isolates was 0.994, and M.
intracellulare resistance to moxifloxacin was significantly more commonly found
in clustered strains than in nonclustered strains (chi(2)=5.551, P=0.040). In
conclusion, our data demonstrated that clarithromycin and capreomycin revealed
highly antimicrobial activities against M. intracellulare isolates, and
clarithromycin and amikacin resistance could be detected more readily and rapidly
using molecular scanning of corresponding drug target than conventional drug
susceptibility testing. We also found that infection by clustered strains was
significantly associated with resistance to moxifloxacin.
PMID- 25131956
TI - Synthesis and biological evaluation of podophyllotoxin congeners as tubulin
polymerization inhibitors.
AB - A series of new podophyllotoxin derivatives containing structural modifications
at C-7, C-8, and C-9 were synthesized and evaluated for their cytotoxic activity
against three human cancer cell lines. All the synthesized compounds showed
significant growth inhibition with GI50 values in micromolar levels while some of
the compounds were several times more potent against MCF-7 and HeLa cell lines
than MIAPACA cell line. Three compounds (12a, 12d and 12e) emerged as potent
compounds with broad spectrum of cytotoxic activity against all the tested cell
lines with GI50 values in the range of 0.01-2.1 MUM. These compounds induce
microtubule depolymerization and arrests cells at the G2/M phase of the cell
cycle. Moreover, compounds 12d and 12e disrupted microtubule network and
accumulated tubulin in the soluble fraction in a similar manner to their parent
podophyllotoxin scaffold. In addition, structure activity relationship studies
within the series were also discussed. Molecular docking studies of these
compounds into the colchicine-binding site of tubulin, revealed possible mode of
inhibition by these compounds.
PMID- 25131957
TI - Development of novel membrane active lipidated peptidomimetics active against
drug resistant clinical isolates.
AB - A new series of small cationic lipidated peptidomimetics have been synthesized
and found to be highly active against several susceptible as well as drug
resistant clinical isolates of bacteria and fungi. All lipidated peptidomimetics
do not cause significant lysis of human erythrocytes (HC50>200MUg/mL). Calcein
dye leakage experiment revealed membranolytic effect of LPEP08 which was further
confirmed by scanning electron microscopy (SEM). The involvement of intracellular
targets as an alternate mode of action was precluded by DNA retardation assay.
Additionally, LPEP08 exhibit high proteolytic stability and dose not elicit
resistance against drug resistant clinical isolate of Staphylococcusaureus, even
after 16 rounds of passaging. These results demonstrate the potential of
lipidated peptidomimetics as biocompatible anti-infective therapeutics.
PMID- 25131959
TI - Natural, engineered, and artificial biocatalysts for organic synthesis.
PMID- 25131958
TI - Ethyl 2-(benzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6
carboxylate analogues as a new scaffold for protein kinase casein kinase 2
inhibitor.
AB - Protein kinase casein kinase 2 (PKCK2) is a constitutively active, growth factor
independent serine/threonine kinase, and changes in PKCK2 expression or its
activity are reported in many cancer cells. To develop a novel PKCK2
inhibitor(s), we first performed cell-based phenotypic screening using 4000
chemicals purchased from ChemDiv chemical libraries (2000: randomly selected;
2000: kinase-biased) and performed in vitro kinase assay-based screening using
hits found from the first screening. We identified compound 24 (C24)[(Z)-ethyl 5
(4-chlorophenyl)-2-(3,4-dihydroxybenzylidene)-7-methyl-3-oxo-3,5-dihydro-2H
thiazolo[3,2-a] pyrimidine-6-carboxylate] as a novel inhibitor of PKCK2 that is
more potent and selective than 4,5,6,7-tetrabromobenzotriazole (TBB). In
particular, compound 24 [half maximal inhibitory concentration (IC50)=0.56MUM]
inhibited PKCK2 2.2-fold more efficiently than did TBB (IC50=1.24MUM), which is
quite specific toward PKCK2 with respect to ATP binding, in a panel of 31 human
protein kinases. The Ki values of compound 24 and TBB for PKCK2 were 0.78MUM and
2.70MUM, respectively. Treatment of cells with compound 24 inhibited endogenous
PKCK2 activity and showed anti-proliferative and pro-apoptotic effects against
stomach and hepatocellular cancer cell lines more efficiently than did TBB. As
expected, compound 24 also enabled tumor necrosis factor-related apoptosis
inducing ligand (TRAIL)-resistant cancer cells to be sensitive toward TRAIL. In
comparing the molecular docking of compound 24 bound to PKCK2alpha versus
previously reported complexes of PKCK2 with other inhibitors, our findings
suggest a new scaffold for specific PKCK2alpha inhibitors. Thus, compound 24
appears to be a selective, cell-permeable, potent, and novel PKCK2 inhibitor
worthy of further characterization.
PMID- 25131960
TI - The Nurse-Based Age Independent Intervention to Limit Evolution of Disease After
Acute Coronary Syndrome (NAILED ACS) Risk Factor Trial: Protocol for a Randomized
Controlled Trial.
AB - BACKGROUND: Secondary prevention after acute coronary syndrome (ACS) is essential
to reduce morbidity and mortality, but related studies have been fairly small or
performed as clinical trials with non-representative patient selection. Long-term
follow-up data are also minimal. A nurse-led follow-up for risk factor
improvement may be effective, but the evidence is limited. OBJECTIVE: The aims of
this study are to perform an adequately sized, nurse-led, long-term secondary
preventive follow-up with inclusion of an unselected population of ACS patients.
The focus will be on lipid and blood pressure control as well as tobacco use and
physical activity. METHODS: The study will consist of a randomized, controlled,
long-term, population-based trial with two parallel groups. Patients will be
included during the initial hospital stay. Important outcome variables are total
cholesterol, low-density lipoprotein (LDL) cholesterol, and sitting systolic and
diastolic blood pressure. Outcomes will be measured after 12, 24, and 36 months
of follow-up. Trained nurses will manage the intervention group with the aim of
achieving set treatment goals as soon as possible. The control group will receive
usual care. At least 250 patients will be included in each group to reliably
detect a difference in mean LDL of 0.5 mmol/L and in mean systolic blood pressure
of 5 mmHg. RESULTS: The study is ongoing and recruitment of participants will
continue until December 31, 2014. CONCLUSIONS: This study will test the
hypothesis that a nurse-led, long-term follow-up after an ACS with a focus on
achieving treatment goals as soon as possible is an effective secondary
preventive method. If proven effective, this method could be implemented in
general practice at a low cost. TRIAL REGISTRATION: International Standard
Randomized Controlled Trial Number (ISRCTN): 96595458; http://www.controlled
trials.com/ISRCTN96595458 (Archived by WebCite at
http://www.webcitation.org/6RlyhYTYK).
PMID- 25131962
TI - Application of isothermal titration calorimetry for characterizing thermodynamic
parameters of biomolecular interactions: peptide self-assembly and protein
adsorption case studies.
AB - The complex nature of macromolecular interactions usually makes it very hard to
identify the molecular-level mechanisms that ultimately dictate the result of
these interactions. This is especially evident in the case of biological systems,
where the complex interaction of molecules in various situations may be
responsible for driving biomolecular interactions themselves but also has a
broader effect at the cell and/or tissue level. This review will endeavor to
further the understanding of biomolecular interactions utilizing the isothermal
titration calorimetry (ITC) technique for thermodynamic characterization of two
extremely important biomaterial systems, viz., peptide self-assembly and
nonfouling polymer-modified surfaces. The advantages and shortcomings of this
technique will be presented along with a thorough review of the recent
application of ITC to these two areas. Furthermore, the controversies associated
with the enthalpy-entropy compensation effect as well as thermodynamic
equilibrium state for such interactions will be discussed.
PMID- 25131964
TI - Quantifying the social impact of research and medical journals.
PMID- 25131961
TI - Translation of clinical trial outcomes to metastatic colorectal cancer patients
in community practice.
AB - AIM: As multiple new agents have been added to the treatment options for patients
with metastatic colorectal cancer, survival outcomes in clinical trials have
continued to improve. Similarly, improved outcomes in routine clinical care would
be anticipated, but have yet to be demonstrated. Here, we aim to explore whether
survival gains demonstrated in clinical trials are reproducible in routine
practice, and whether factors beyond new therapies may be contributing to
improved outcomes. METHODS: Comparison of comprehensive treatment and outcome
data for consecutive patients diagnosed in 2003-2006 versus 2007-2010 at four
specialist hospitals in Australia. RESULTS: Data were available on 965 patients;
median age 66.1 years (range 19-93), 572 (59%) were male. For the latter time
period, there was an increase in patients receiving any treatment (74% vs 66%, P
= 0.014), initial combination chemotherapy (57% vs 44%, P < 0.001) and
bevacizumab (15% vs 2%, P < 0.001). There was no change in the percentage
undergoing resection of distant metastatic disease. For the latter time period,
overall survival was improved (median 24.8 vs 17.4 months, P < 0.001), including
patients not receiving any active treatment (11.9 vs 6.4 months, P = 0.014).
CONCLUSION: Survival outcomes in routine clinical care for patients with
metastatic colorectal cancer have markedly improved in recent years following the
introduction of multiple new active therapies. The improved outcome of untreated
patients suggests earlier diagnosis and improved supportive care may also be
contributing to survival gains.
PMID- 25131963
TI - Multi-modality management for loco-regionally advanced laryngeal and
hypopharyngeal cancer: balancing the benefit of efficacy and functional
preservation.
AB - The 5-year overall survival (OS) of loco-regionally advanced laryngeal and
hypopharyngeal carcinoma (LA-LHC) has declined over the past two decades
following the wide application of non-surgical approaches. We aimed to define the
new role of open surgery combined with adjuvant chemoradiotherapy in the
treatment of LA-LHC for improving survival while maintaining a functional larynx.
In the current study, 90 LA-LHC patients treated with open surgery followed by
postoperative RT/CRT in our institute from May 2005 to December 2012 were
retrospectively analyzed. OS, disease-free survival (DFS), loco-regional failure
free survival (LRFFS) and distant metastasis-free survival (DMFS) were
calculated, and prognostic factors were analyzed. Functional larynx preservation
results were evaluated according to the head and neck quality of life (QoL)
Scale. With a median follow-up period of 37 months, the 3- and 5-year OS, DFS,
LRFFS and DMFS were 71.3, 63.7, 85.9, 73.7 and 55.9, 53.0, 81.6, 71.9 %,
respectively. Vascular embolism and extracapsular extension (ECE) of the lymph
nodes were prognostic factors for poorer OS (p = 0.045 and 0.046, respectively).
Vascular embolism was the only prognostic factor for poorer DMFS (p = 0.005).
Patients who underwent a conservative partial laryngectomy (CPL) experienced a
higher QoL in the domains of speech, swallowing and emotion. Functional larynx
preservation was achieved in 36/45 patients (80 %) who received CPL. The results
of our study demonstrated that CPL followed by adequate adjuvant therapy could
achieve superior oncological results compared with non-surgical approaches in LA
LHC patients while also maintaining satisfactory functional larynx in a majority
of patients.
PMID- 25131965
TI - Prescribing antibiotics: a battle of resistance.
PMID- 25131966
TI - Priorities for people with disabilities in New Zealand.
PMID- 25131967
TI - Under-use of the Ross operation--a lost opportunity.
PMID- 25131968
TI - Telemonitoring implants for patients with heart failure.
PMID- 25131969
TI - Risk and decision making in patients with hypertension.
PMID- 25131970
TI - Heparin monotherapy for percutaneous coronary intervention?
PMID- 25131971
TI - Dyslipidaemia in perspective.
PMID- 25131973
TI - Adhesion barriers for abdominal surgery and oncology.
PMID- 25131974
TI - Adhesion barriers for abdominal surgery and oncology - Authors' reply.
PMID- 25131975
TI - Better treatment of XDR tuberculosis needed in South Africa.
PMID- 25131976
TI - Better treatment of XDR tuberculosis needed in South Africa - Author's reply.
PMID- 25131977
TI - Implant-based multiparameter telemonitoring of patients with heart failure (IN
TIME): a randomised controlled trial.
AB - BACKGROUND: An increasing number of patients with heart failure receive
implantable cardioverter-defibrillators (ICDs) or cardiac resynchronisation
defibrillators (CRT-Ds) with telemonitoring function. Early detection of
worsening heart failure, or upstream factors predisposing to worsening heart
failure, by implant-based telemonitoring might enable pre-emptive intervention
and improve outcomes, but the evidence is weak. We investigated this possibility
in IN-TIME, a clinical trial. METHODS: We did this randomised, controlled trial
at 36 tertiary clinical centres and hospitals in Australia, Europe, and Israel.
We enrolled patients with chronic heart failure, NYHA class II-III symptoms,
ejection fraction of no more than 35%, optimal drug treatment, no permanent
atrial fibrillation, and a recent dual-chamber ICD or CRT-D implantation. After a
1 month run-in phase, patients were randomly assigned (1:1) to either automatic,
daily, implant-based, multiparameter telemonitoring in addition to standard care
or standard care without telemonitoring. Investigators were not masked to
treatment allocation. Patients were masked to allocation unless they were
contacted because of telemonitoring findings. Follow-up was 1 year. The primary
outcome measure was a composite clinical score combining all-cause death,
overnight hospital admission for heart failure, change in NYHA class, and change
in patient global self-assessment, for the intention-to-treat population. The
trial is registered with ClinicalTrials.gov, number NCT00538356. FINDINGS: We
enrolled 716 patients, of whom 664 were randomly assigned (333 to telemonitoring,
331 to control). Mean age was 65.5 years and mean ejection fraction was 26%. 285
(43%) of patients had NYHA functional class II and 378 (57%) had NYHA class III.
Most patients received CRT-Ds (390; 58.7%). At 1 year, 63 (18.9%) of 333 patients
in the telemonitoring group versus 90 (27.2%) of 331 in the control group
(p=0.013) had worsened composite score (odds ratio 0.63, 95% CI 0.43-0.90). Ten
versus 27 patients died during follow-up. INTERPRETATION: Automatic, daily,
implant-based, multiparameter telemonitoring can significantly improve clinical
outcomes for patients with heart failure. Such telemonitoring is feasible and
should be used in clinical practice. FUNDING: Biotronik SE & Co. KG.
PMID- 25131978
TI - Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis
of individual patient data.
AB - BACKGROUND: We aimed to investigate whether the benefits of blood pressure
lowering drugs are proportional to baseline cardiovascular risk, to establish
whether absolute risk could be used to inform treatment decisions for blood
pressure-lowering therapy, as is recommended for lipid-lowering therapy. METHODS:
This meta-analysis included individual participant data from trials that randomly
assigned patients to either blood pressure-lowering drugs or placebo, or to more
intensive or less intensive blood pressure-lowering regimens. The primary outcome
was total major cardiovascular events, consisting of stroke, heart attack, heart
failure, or cardiovascular death. Participants were separated into four
categories of baseline 5-year major cardiovascular risk using a risk prediction
equation developed from the placebo groups of the included trials (<11%, 11-15%,
15-21%, >21%). FINDINGS: 11 trials and 26 randomised groups met the inclusion
criteria, and included 67,475 individuals, of whom 51,917 had available data for
the calculation of the risk equations. 4167 (8%) had a cardiovascular event
during a median of 4.0 years (IQR 3.4-4.4) of follow-up. The mean estimated
baseline levels of 5-year cardiovascular risk for each of the four risk groups
were 6.0% (SD 2.0), 12.1% (1.5), 17.7% (1.7), and 26.8% (5.4). In each
consecutive higher risk group, blood pressure-lowering treatment reduced the risk
of cardiovascular events relatively by 18% (95% CI 7-27), 15% (4-25), 13% (2-22),
and 15% (5-24), respectively (p=0.30 for trend). However, in absolute terms,
treating 1000 patients in each group with blood pressure-lowering treatment for 5
years would prevent 14 (95% CI 8-21), 20 (8-31), 24 (8-40), and 38 (16-61)
cardiovascular events, respectively (p=0.04 for trend). INTERPRETATION: Lowering
blood pressure provides similar relative protection at all levels of baseline
cardiovascular risk, but progressively greater absolute risk reductions as
baseline risk increases. These results support the use of predicted baseline
cardiovascular disease risk equations to inform blood pressure-lowering treatment
decisions. FUNDING: None.
PMID- 25131979
TI - Bivalirudin versus heparin in patients planned for percutaneous coronary
intervention: a meta-analysis of randomised controlled trials.
AB - BACKGROUND: Bivalirudin is an alternative to heparin in patients undergoing
percutaneous coronary intervention (PCI). We aimed to define the effects of a
bivalirudin-based anticoagulation regimen compared with a heparin-based
anticoagulation regimen on ischaemic and bleeding outcomes. METHODS: We searched
Medline, the Cochrane Library, and relevant meeting abstracts (search done on
April 9, 2014) for randomised trials that assessed bivalirudin versus heparin in
patients planned for PCI. The primary efficacy endpoint was the incidence of
major adverse cardiac events (MACE) up to 30 days. Secondary efficacy endpoints
were death, myocardial infarction, ischaemia-driven revascularisation, and stent
thrombosis. The primary safety endpoint was major bleeding up to 30 days. We
calculated pooled risk ratios and 95% CIs using random-effects models. FINDINGS:
We included data from 16 trials involving 33 958 patients, of whom 2422
experienced MACE and 1406 had a major bleed. There was an increase in the risk of
MACE with bivalirudin-based regimens compared with heparin-based regimens (risk
ratio 1.09, 95% CI 1.01-1.17; p=0.0204), which was largely driven by increases in
myocardial infarction (1.12, 1.03-1.23) and seemingly also by ischaemia-driven
revascularisation (1.16, 0.997-1.34) with bivalirudin compared with heparin, with
no effect on mortality (0.99, 0.82-1.18). Bivalirudin increased the risk of stent
thrombosis (risk ratio 1.38, 95% CI 1.09-1.74; p=0.0074), which was primarily due
to an increase in acute cases in ST-segment elevation myocardial infarction
(4.27, 2.28-8.00; p<0.0001). Overall, bivalirudin-based regimens lowered the risk
of major bleeding (risk ratio 0.62, 95% CI 0.49-0.78; p<0.0001), but the
magnitude of this effect varied greatly (p<0.0001) depending on whether
glycoprotein IIb/IIIa inhibitors were used predominantly in the heparin arm only
(0.53, 0.47-0.61; p<0.0001), provisionally in both arms (0.78, 0.51-1.19;
p=0.25), or planned in both arms (1.07, 0.87-1.31; p=0.53). INTERPRETATION:
Compared with a heparin-based regimen, a bivalirudin-based regimen increases the
risk of myocardial infarction and stent thrombosis, but decreases the risk of
bleeding, with the magnitude of the reduction depending on concomitant
glycoprotein IIb/IIIa inhibitor use. Physicians should weigh the trade-off
between ischaemic and bleeding events when choosing between different
anticoagulant regimens. FUNDING: None.
PMID- 25131980
TI - LDL cholesterol: controversies and future therapeutic directions.
AB - Lifelong exposure to raised concentrations of LDL cholesterol increases
cardiovascular event rates, and the use of statin therapy as an adjunct to diet,
exercise, and smoking cessation has proven highly effective in reducing the
population burden associated with hyperlipidaemia. Yet, despite consistent
biological, genetic, and epidemiological data, and evidence from randomised
trials, there is controversy among national guidelines and clinical practice with
regard to LDL cholesterol, its measurement, the usefulness of population-based
screening, the net benefit-to-risk ratio for different LDL-lowering drugs, the
benefit of treatment targets, and whether aggressive lowering of LDL is safe.
Several novel therapies have been introduced for the treatment of people with
genetic defects that result in loss of function within the LDL receptor, a major
determinant of inherited hyperlipidaemias. Moreover, the usefulness of monoclonal
antibodies that extend the LDL-receptor lifecycle (and thus result in substantial
lowering of LDL cholesterol below the levels achieved with statins alone) is
being assessed in phase 3 trials that will enrol more than 60,000 at-risk
patients worldwide. These trials represent an exceptionally rapid translation of
genetic observations into clinical practice and will address core questions of
how low LDL cholesterol can be safely reduced, whether the mechanism of LDL
cholesterol lowering matters, and whether ever more aggressive lipid-lowering
provides a safe, long-term mechanism to prevent atherothrombotic complications.
PMID- 25131981
TI - HDL and cardiovascular disease.
AB - The cholesterol contained within HDL is inversely associated with risk of
coronary heart disease and is a key component of predicting cardiovascular risk.
However, despite its properties consistent with atheroprotection, the causal
relation between HDL and atherosclerosis is uncertain. Human genetics and failed
clinical trials have created scepticism about the HDL hypothesis. Nevertheless,
drugs that raise HDL-C concentrations, cholesteryl ester transfer protein
inhibitors, are in late-stage clinical development, and other approaches that
promote HDL function, including reverse cholesterol transport, are in early-stage
clinical development. The final chapters regarding the effect of HDL-targeted
therapeutic interventions on coronary heart disease events remain to be written.
PMID- 25131982
TI - Triglycerides and cardiovascular disease.
AB - After the introduction of statins, clinical emphasis first focussed on LDL
cholesterol-lowering, then on the potential for raising HDL cholesterol, with
less focus on lowering triglycerides. However, the understanding from genetic
studies and negative results from randomised trials that low HDL cholesterol
might not cause cardiovascular disease as originally thought has now generated
renewed interest in raised concentrations of triglycerides. This renewed interest
has also been driven by epidemiological and genetic evidence supporting raised
triglycerides, remnant cholesterol, or triglyceride-rich lipoproteins as an
additional cause of cardiovascular disease and all-cause mortality. Triglycerides
can be measured in the non-fasting or fasting states, with concentrations of 2-10
mmol/L conferring increased risk of cardiovascular disease, and concentrations
greater than 10 mmol/L conferring increased risk of acute pancreatitis and
possibly cardiovascular disease. Although randomised trials showing
cardiovascular benefit of triglyceride reduction are scarce, new triglyceride
lowering drugs are being developed, and large-scale trials have been initiated
that will hopefully provide conclusive evidence as to whether lowering
triglycerides reduces the risk of cardiovascular disease.
PMID- 25131983
TI - Acute retinal necrosis presenting as bilateral acute angle closure.
PMID- 25131984
TI - Incidence, management, and prevention of right ventricular perforation by
pacemaker and implantable cardioverter defibrillator leads.
AB - BACKGROUND: Cardiac perforation of the right ventricle (RV) is a rare but
potentially life-threatening complication of both pacemaker (PM) and implantable
cardioverter defibrillator (ICD) implant. Appropriate management is still
uncertain. We assessed the incidence of subacute (24 hours-1 month) or delayed
(>1 month) cardiac perforation by RV lead and the results of percutaneous lead
extraction. METHOD: The study population included all patients diagnosed with
subacute or delayed RV-lead perforation during the period 2007-2013. The
incidence of perforation according to device type and fixation mechanism was
calculated. The outcome of the percutaneous approach, consisting of lead
extraction by simple traction, was assessed. RESULTS: Cardiac perforation was
diagnosed in 14 (eight females, mean age 71 [range 47-83] years) patients out of
3,815 who received an RV-lead implant (0.4%). The overall incidence of RV-lead
perforation was similar between ICD (0.3%) and PM (0.4%) implants (P = 1.0) and
between active (0.5%) and passive (0.3%) fixation leads (P = 0.3). All
perforating leads were originally placed at the RV apex. Five patients were
asymptomatic, but all presented altered lead electrical parameters. Surgical
removal of the lead was performed in one patient while in the remaining the leads
were successfully extracted by direct manual traction in the absence of any
complications. In all patients, new active fixation leads were positioned in the
RV septum and the follow-up (42 +/- 27 months) was uneventful. CONCLUSIONS: RV
perforation is a rare complication of both PM and ICD implants, regardless of the
lead fixation mechanism. In most patients, percutaneous lead extraction is a safe
and effective management approach.
PMID- 25131986
TI - Ebola in West Africa.
PMID- 25131985
TI - Current use of metformin in addition to insulin in pediatric patients with type 1
diabetes mellitus: an analysis based on a large diabetes registry in Germany and
Austria.
AB - BACKGROUND: With increasing obesity in childhood and adolescence, weight gain,
and insulin resistance become also more frequent in patients with type 1 diabetes
mellitus (T1DM). Especially during puberty, insulin therapy often has to be
intensified and higher insulin doses are necessary. Some studies point to a
beneficial effect of metformin in addition to insulin in these patients. In order
to describe current practice and possible benefits, we compared pediatric T1DM
patients with insulin plus metformin (n = 525) to patients with insulin therapy
only (n = 57 487) in a prospective multicenter analysis. METHODS: Auxological and
treatment data from 58 012 patients aged <21 yr with T1DM in the German/Austrian
Diabetes Patienten Verlaufsdokumentation (DPV) registry were analyzed by
multivariable mixed regression modeling. RESULTS: Patients with additional
metformin were older [median (interquartile range)]: [16.1 (14.1-17.6) vs. 15.2
(11.5-17.5) yr] with female preponderance (61.0 vs. 47.2%, p < 0.01). They had
higher body mass index-standard deviation score (BMI-SDS) [+2.03 (+1.29 to +2.56)
vs. +0.51 (-0.12 to +1.15); p < 0.01] and glycated hemoglobin (HbA1c) (9.0 vs.
8.6%, p < 0.01). Hypertension (43.7 vs. 24.8%) and dyslipidemia (58.4 vs. 40.6%)
were significantly more prevalent. Adjusted insulin dose was significantly higher
(0.98 vs. 0.93 IU/kg bodyweight). In a subgroup of 285 patients followed-up
longitudinally (average treatment period 1.42 yr), addition of metformin resulted
in a slight reduction of BMI-SDS [-0.01 (-2.01 to +1.40)], but did not improve
HbA1c or insulin requirement. CONCLUSION: Additional metformin therapy in T1DM is
primarily used in obese females. Additional therapy with metformin was associated
with minor benefits.
PMID- 25131987
TI - Seeing the forest, but not the trees: pertinent considerations for examining
acute changes in pulse wave velocity in response to pharmaceutical interventions
and exercise.
PMID- 25131988
TI - Expression of perilipin 2 (PLIN2) in porcine oocytes during maturation.
AB - Perilipins have been reported to limit the interaction of lipases with neutral
lipids within the droplets, thereby regulating neutral lipid accumulation and
utilization. This study aimed to identify the location and expression of PLIN1
and PLIN2 in porcine oocytes during maturation. Quantitative real-time polymerase
chain reaction (qRT-PCR), immunostaining and Western blot methods were used to
characterize the expression and distribution patterns of PLIN1 and PLIN2 in
porcine oocytes. The results showed that PLIN1 was not detectable in porcine
oocytes. PLIN2 and BODIPY 493/503-detected neutral lipid droplets appeared
identical distribution patterns and extensive colocalization in both GV and MII
porcine oocytes. PLIN2 protein expression was higher in GV oocytes than that in
MII oocytes (p < 0.05), although PLIN2 mRNA expression was similar in both
groups. These findings suggested that PLIN2 was a major lipid droplet-associated
protein in porcine oocytes.
PMID- 25131990
TI - Structure-guided reprogramming of human cGAS dinucleotide linkage specificity.
AB - Cyclic dinucleotides (CDNs) play central roles in bacterial pathogenesis and
innate immunity. The mammalian enzyme cGAS synthesizes a unique cyclic
dinucleotide (cGAMP) containing a 2'-5' phosphodiester linkage essential for
optimal immune stimulation, but the molecular basis for linkage specificity is
unknown. Here, we show that the Vibrio cholerae pathogenicity factor DncV is a
prokaryotic cGAS-like enzyme whose activity provides a mechanistic rationale for
the unique ability of cGAS to produce 2'-5' cGAMP. Three high-resolution crystal
structures show that DncV and human cGAS generate CDNs in sequential reactions
that proceed in opposing directions. We explain 2' and 3' linkage specificity and
test this model by reprogramming the human cGAS active site to produce 3'-5'
cGAMP, leading to selective stimulation of alternative STING adaptor alleles in
cells. These results demonstrate mechanistic homology between bacterial signaling
and mammalian innate immunity and explain how active site configuration controls
linkage chemistry for pathway-specific signaling.
PMID- 25131989
TI - Broadly neutralizing antibodies and viral inducers decrease rebound from HIV-1
latent reservoirs in humanized mice.
AB - Latent reservoirs of HIV-1-infected cells are refractory to antiretroviral
therapies (ART) and remain the major barrier to curing HIV-1. Because latently
infected cells are long-lived, immunologically invisible, and may undergo
homeostatic proliferation, a "shock and kill" approach has been proposed to
eradicate this reservoir by combining ART with inducers of viral transcription.
However, all attempts to alter the HIV-1 reservoir in vivo have failed to date.
Using humanized mice, we show that broadly neutralizing antibodies (bNAbs) can
interfere with establishment of a silent reservoir by Fc-FcR-mediated mechanisms.
In established infection, bNAbs or bNAbs plus single inducers are ineffective in
preventing viral rebound. However, bNAbs plus a combination of inducers that act
by independent mechanisms synergize to decrease the reservoir as measured by
viral rebound. Thus, combinations of inducers and bNAbs constitute a therapeutic
strategy that impacts the establishment and maintenance of the HIV-1 reservoir in
humanized mice.
PMID- 25131992
TI - Surface characteristics and microbial adherence ability of modified
polymethylmethacrylate by fluoridated glass fillers.
AB - BACKGROUND: The current study objectives were to evaluate the influence of
fluoridated glass fillers loading on the surface roughness, wettability, and
adherence of candida and bacteria with and without saliva presence to a
polymethylmethacrylate (PMMA) denture base material surface. METHODS: Four
concentrations of fluoridated glass fillers were added to PMMA: 1%, 2.5%, 5% and
10% by weight pre-polymerization and 0% was the control. Discs of each
concentration were fabricated (n = 5 for each variable). Surface roughness (Ra )
was measured using atomic force microscopy (AFM). Wettability was assessed by
measuring the contact angle of a sessile drop of water. Specimens were incubated
with Candida albicans, or Streptococcus mutans with and without saliva coating.
Adherence was presented as a percentage of the colonized surface area, counted
using an optical microscope at x100 magnification. RESULTS: The 10% group showed
significantly greater roughness than the control and 1% groups; however, no
significant differences in contact angle values were detected. The microbial
adhesion was inversely proportional to the fluoridated glass fillers
concentration where 10% concentration significantly decreased candidal and
bacterial adhesion compared to others. Saliva coating significantly decreased
microbial adhesion. CONCLUSIONS: It was concluded that fluoridated glass fillers
could decrease microbial adhesion to acrylic denture base without adversely
affecting surface properties.
PMID- 25131993
TI - MLPA Application in Clinical Diagnosis of DMD/BMD in Shanghai.
AB - BACKGROUND: Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked
recessive disorders caused by mutation in dystrophin gene. We reported 3-year
clinic experience from a single hospital in Shanghai using multiplex ligation
dependent probe amplification (MLPA) assay to detect DMD mutations. METHODS: Four
hundred and fifty-one males and 184 females, who were clinically diagnosed as
DMD/BMD patients or carriers at our hospital's outpatient clinic, were collected
and performed with MLPA to detect DMD gene mutations. RESULTS: Seventeen novel
mutation points not reported in the Leiden Muscular Dystrophy pages were
identified in this study. We found that the most frequent deletion spots ranged
from exon45 to exon52, and exon2, exon19 were the two most frequently detected
duplication spots. CONCLUSION: The results of our study confirmed MLPA as an
efficient clinical method for detecting DMD gene mutations in DMD/BMD patients.
Single exon mutation detected by MLPA should be verified by other methods, and we
should emphasize that only precise clinical molecular diagnosis can lead to the
feasibility of prenatal diagnosis.
PMID- 25131994
TI - Selective CH functionalization of methane, ethane, and propane by a
perfluoroarene iodine(III) complex.
AB - Direct partial oxidation of methane, ethane, and propane to their respective
trifluoroacetate esters is achieved by a homogeneous hypervalent iodine(III)
complex in non-superacidic (trifluoroacetic acid) solvent. The reaction is highly
selective for ester formation (>99%). In the case of ethane, greater than 0.5 M
EtTFA can be achieved. Preliminary kinetic analysis and density functional
calculations support a nonradical electrophilic CH activation and iodine alkyl
functionalization mechanism.
PMID- 25131991
TI - Expression of alpha-subunit of alpha-glucosidase II in adult mouse brain regions
and selected organs.
AB - alpha-Glucosidase II (GII), a resident of endoplasmic reticulum (ER) and an
important enzyme in the folding of nascent glycoproteins, is heterodimeric,
consisting of alpha (GIIalpha) and beta (GIIbeta) subunits. The catalytic
GIIalpha subunit, with the help of mannose 6-phosphate receptor homology domain
of GIIbeta, sequentially hydrolyzes two alpha1-3-linked glucose residues in the
second step of N-linked oligosaccharide-mediated protein folding. The soluble
GIIalpha subunit is retained in the ER through its interaction with the HDEL
containing GIIbeta subunit. N-glycosylation and correct protein folding are
crucial for protein stability and trafficking and cell surface expression of
several proteins in the brain. Alterations in N-glycosylation lead to
abnormalities in neuronal migration and mental retardation, various
neurodegenerative diseases, and invasion of malignant gliomas. Inhibitors of GII
are used to inhibit cell proliferation and migration in a variety of different
pathologies, such as viral infection, cancer, and diabetes. Despite the
widespread use of GIIalpha inhibitory drugs and the role of GIIalpha in brain
function, little is known about its expression in brain and other tissues. Here,
we report generation of a highly specific chicken antibody to the GIIalpha
subunit and its characterization by Western blotting and immunoprecipitation
using cerebral cortical extracts. By using this antibody, we showed that the
GIIalpha protein is highly expressed in testis, kidney, and lung, with the lowest
amount in heart. GIIalpha polypeptide levels in whole brain were comparable to
those in spleen. However, a higher expression of GIIalpha protein was detected in
the cerebral cortex, reflecting its continuous requirement in correct folding of
cell surface proteins.
PMID- 25131995
TI - Bibliometric performance of Acta Physiologica.
PMID- 25131998
TI - Nomenclature for factors of the HLA system, update May 2014.
PMID- 25131997
TI - Gallic acid regulates skin photoaging in UVB-exposed fibroblast and hairless
mice.
AB - Ultraviolet (UV) radiation is the primary factor in skin photoaging, which is
characterized by wrinkle formation, dryness, and thickening. The mechanisms
underlying skin photoaging are closely associated with degradation of collagen
via upregulation of matrix metalloproteinase (MMP) activity, which is induced by
reactive oxygen species (ROS) production. Gallic acid (GA), a phenolic compound,
possesses a variety of biological activities including antioxidant and
antiinflammatory activities. We investigated the protective effects of GA against
photoaging caused by UVB irradiation using normal human dermal fibroblasts
(NHDFs) in vitro and hairless mice in vivo. The production levels of ROS,
interlukin-6, and MMP-1 were significantly suppressed, and type I procollagen
expression was stimulated in UVB-irradiated and GA-treated NHDFs. GA treatment
inhibited the activity of transcription factor activation protein 1. The effects
of GA following topical application and dietary administration were examined by
measuring wrinkle formation, histological modification, protein expression, and
physiological changes such as stratum corneum hydration, transepidermal water
loss, and erythema index. We found that GA decreased dryness, skin thickness, and
wrinkle formation via negative modulation of MMP-1 secretion and positive
regulation of elastin, type I procollagen, and transforming growth factor-beta1.
Our data indicate that GA is a potential candidate for the prevention of UVB
induced premature skin aging.
PMID- 25131996
TI - Synchronous multiscale neuroimaging environment for critically sampled
physiological analysis of brain function: hepta-scan concept.
AB - Functional connectivity of the resting-state networks of the brain is thought to
be mediated by very-low-frequency fluctuations (VLFFs <0.1 Hz) in neuronal
activity. However, vasomotor waves and cardiorespiratory pulsations influence
indirect measures of brain function, such as the functional magnetic resonance
imaging blood-oxygen-level-dependent (BOLD) signal. How strongly physiological
oscillations correlate with spontaneous BOLD signals is not known, partially due
to differences in the data-sampling rates of different methods. Recent ultrafast
inverse imaging sequences, including magnetic resonance encephalography (MREG),
enable critical sampling of these signals. In this study, we describe a
multimodal concept, referred to as Hepta-scan, which incorporates synchronous
MREG with scalp electroencephalography, near-infrared spectroscopy, noninvasive
blood pressure, and anesthesia monitoring. Our preliminary results support the
idea that, in the absence of aliased cardiorespiratory signals, VLFFs in the BOLD
signal are affected by vasomotor and electrophysiological sources. Further, MREG
signals showed a high correlation coefficient between the ventromedial default
mode network (DMNvmpf) and electrophysiological signals, especially in the VLF
range. Also, oxy- and deoxyhemoglobin and vasomotor waves were found to correlate
with DMNvmpf. Intriguingly, usage of shorter time windows in these correlation
measurements produced significantly (p<0.05) higher positive and negative
correlation coefficients, suggesting temporal nonstationary behavior between the
measurements. Focus on the VLF range strongly increased correlation strength.
PMID- 25131999
TI - Chronological changes in the microstructure of bone during peri-implant healing:
a microcomputed tomographic evaluation.
AB - Our objectives were to examine the titanium-bone interfaces chronologically and
to clarify the process of osseointegration using microcomputed tomography
(microCT). The mandibular premolars of 3 dogs were extracted and 12 weeks later 2
Straumann dental implants were installed in each quadrant. The microstructural
changes at the bone-implant interface at the first, fourth, and eighth weeks
after installation were evaluated by microCT and a 3-dimensional image was
constructed. The microstructural measurements at the bone-implant interface,
including the trabecular number (Tb.N), bone volume fraction (BV/TV), structure
model index (SMI), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp)
and connectivity density (Conn.D), were measured. Experimental outcomes were
analysed for correlations between time and microstructural variables of
trabecular bone. Tb.N increased significantly during the eighth week compared
with that during the first and fourth week (p=0.001, 0.002). BV/TV increased
generally with time and there were significant differences (p=0.003) between each
time group. While Tb.Sp decreased with time and changed significantly during the
eighth week compared with that during the first week (p=0.021), differences in
SMI, Tb.Th and Conn.D did not differ significantly according to time of implant.
The significant increase in the Tb.N and BV/TV during the eighth week after
insertion of implants indicates that the formation of new bone before the eighth
week is the key to osseointegration.
PMID- 25132000
TI - Keloids in Rubinstein-Taybi syndrome: a clinical study.
AB - BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a multiple congenital anomalies
intellectual disability syndrome. One of the complications is keloid formation.
Keloids are proliferative fibrous growths resulting from excessive tissue
response to skin trauma. OBJECTIVES: To describe the clinical characteristics of
keloids in individuals with RSTS reported in the literature and in a cohort of
personally evaluated individuals with RSTS. PATIENTS AND METHODS: We performed a
literature search for descriptions of RSTS individuals with keloids. All known
individuals with RSTS in the Netherlands filled out three dedicated
questionnaires. All individuals with (possible) keloids were personally
evaluated. A further series of individuals with RSTS from the U.K. was personally
evaluated. RESULTS: Reliable data were available for 62 of the 83 Dutch
individuals with RSTS and showed 15 individuals with RSTS (24%) to have keloids.
The 15 Dutch and 12 U.K. individuals with RSTS with keloids demonstrated that
most patients have multiple keloids (n > 1: 82%; n > 5: 30%). Mean age of onset
is 11.9 years. The majority of keloids are located on the shoulders and chest.
The mean length * width of the largest keloid was 7.1 * 2.8 cm, and the mean
thickness was 0.7 cm. All affected individuals complained of itching. Generally,
treatment results were disappointing. CONCLUSIONS: Keloids occur in 24% of
individuals with RSTS, either spontaneously or after a minor trauma, usually
starting in early puberty. Management schedules have disappointing results. RSTS
is a Mendelian disorder with a known molecular basis, and offers excellent
opportunities to study the pathogenesis of keloids in general and to search for
possible treatments.
PMID- 25132001
TI - Development of a highly-potent anti-angiogenic VEGF8-109 heterodimer by directed
blocking of its VEGFR-2 binding site.
AB - Angiogenesis is a hallmark of various pathological conditions and is controlled
by a variety of angiogenic factors. Blockade of vascular endothelial growth
factor (VEGF) as the most pivotal stimulator of angiogenesis offers a promising
therapeutic approach for some diseases, typically cancer. In the present study, a
heterodimeric antagonistic VEGF was precisely designed based on structural
information of recently-crystallized VEGF/VEGF receptor-2 (VEGFR-2/fetal liver
kinase 1/kinase domain region) complex. Directed blocking of kinase domain region
occurs via substitution of a VEGF receptor binding site by two peptide segments
in one pole, whereas the binding domain of the other pole of VEGF was intact.
Candidate peptides for substitution were selected considering to some sequence
and structural criteria. A reliable model of modified VEGF was built, refined
using molecular dynamics simulation and docked with VEGFR-2. Docking analysis
revealed that binding affinity of mutant VEGF was notably diminished,
corroborating our design. Heterodimeric VEGF was expressed, refolded and highly
purified by two-step affinity chromatography. Dimerization of this antagonist was
confirmed using some analytical techniques. Spectroscopic studies assured us to
obtain the heterodimeric form of VEGF. Some angiogenic in vitro assays such
endothelial cell proliferation and tube formation indicated that this antagonist
is not only strongly capable of inhibiting angiogenesis (half maximal inhibitory
concentration of 33 and 24 ng . mL(-1) , respectively), but also showed the
highest inhibitory effect compared to all other heterodimeric VEGF variants. The
high anti-angiogenic potency of this VEGF antagonist may allow its future use as
an anti-tumor agent.
PMID- 25132002
TI - On fragmenting, densely mineralised acellular protrusions into articular
cartilage and their possible role in osteoarthritis.
AB - High density mineralised protrusions (HDMP) from the tidemark mineralising front
into hyaline articular cartilage (HAC) were first described in Thoroughbred
racehorse fetlock joints and later in Icelandic horse hock joints. We now report
them in human material. Whole femoral heads removed at operation for joint
replacement or from dissection room cadavers were imaged using magnetic resonance
imaging (MRI) dual echo steady state at 0.23 mm resolution, then 26-MUm
resolution high contrast X-ray microtomography, sectioned and embedded in
polymethylmethacrylate, blocks cut and polished and re-imaged with 6-MUm
resolution X-ray microtomography. Tissue mineralisation density was imaged using
backscattered electron SEM (BSE SEM) at 20 kV with uncoated samples. HAC
histology was studied by BSE SEM after staining block faces with ammonium
triiodide solution. HDMP arise via the extrusion of an unknown mineralisable
matrix into clefts in HAC, a process of acellular dystrophic calcification. Their
formation may be an extension of a crack self-healing mechanism found in bone and
articular calcified cartilage. Mineral concentration exceeds that of articular
calcified cartilage and is not uniform. It is probable that they have not been
reported previously because they are removed by decalcification with standard
protocols. Mineral phase morphology frequently shows the agglomeration of many
fine particles into larger concretions. HDMP are surrounded by HAC, are brittle,
and show fault lines within them. Dense fragments found within damaged HAC could
make a significant contribution to joint destruction. At least larger HDMP can be
detected with the best MRI imaging ex vivo.
PMID- 25132005
TI - Cardiolipin profiles as a potential biomarker of mitochondrial health in diet
induced obese mice subjected to exercise, diet-restriction and ephedrine
treatment.
AB - Cardiolipin (CL) is crucial for mitochondrial energy metabolism and structural
integrity. Alterations in CL quantity or CL species have been associated with
mitochondrial dysfunction in several pathological conditions and diseases,
including mitochondrial dysfunction-related compound attrition and post-market
withdrawal of promising drugs. Here we report alterations in the CL profiles in
conjunction with morphology of soleus muscle (SM) and brown adipose tissue (BAT)
in diet-induced obese (DIO) mice, subjected to ephedrine treatment (EPH: 200 mg
kg(-1) day(-1) orally), treadmill exercise (EX: 10 meters per min, 1 h per day),
or dietary restriction (DR: 25% less of mean food consumed by the EX group) for 7
days. Mice from the DR and EPH groups had a significant decrease in percent body
weight and reduced fat mass compared with DIO controls. Morphologic alterations
in the BAT included brown adipocytes with reduced cytoplasmic lipid droplets and
increased cytoplasmic eosinophilia in the EX, DR and EPH groups. Increased
cytoplasmic eosinophilia in the BAT was ultrastructurally manifested by increased
mitochondrial cristae, fenestration of mitochondrial cristae, increased electron
density of mitochondrial matrix, and increased complexity of shape and elongation
of mitochondria. Mitochondrial ultrastructural alterations in the SM of the EX
and DR groups included increased mitochondrial cristae, cup-shaped mitochondria
and mitochondrial degeneration. All four CL species (tri-linoleoyl-mono
docosahexaenoyl, tetralinoleoyl, tri-linoleoyl-mono-oleoyl, and di-linoleoyl-di
oleoyl) were increased in the BAT of the DR and EPH groups and in the SM of the
EPH and EX groups. In conclusion, cardiolipin profiling supported standard
methods for assessing mitochondrial biogenesis and health, and may serve as a
potential marker of mitochondrial dysfunction in preclinical toxicity studies.
PMID- 25132004
TI - Outcome of surgery for pancreatic neuroendocrine neoplasms.
AB - BACKGROUND: The incidence of pancreatic neuroendocrine neoplasms (pNEN) is
increasing. This study aimed to evaluate predictors of overall survival and the
indication for surgery. METHODS: Data collected between October 2001 and December
2012 were analysed. Histological grading and staging was based on the
classifications of the World Health Organization, the International Union Against
Cancer and the European Neuroendocrine Tumour Society. RESULTS: Some 310 patients
(150 female, 48.4 per cent) underwent surgical resection. The final survival
analysis included 291 patients. Five-year overall survival differed according to
tumour grade (G): 91.0 per cent among 156 patients with pancreatic neuroendocrine
tumours (pNET) G1, 70.8 per cent in 111 patients with pNET G2, and 20 per cent in
24 patients with pancreatic neuroendocrine carcinomas (pNEC) G3 (P < 0.001).
Tumours graded G3 (hazard ratio (HR) 6.96, 95 per cent confidence interval 3.67
to 13.21), the presence of distant metastasis (HR 2.41, 1.32 to 4.42) and lymph
node metastasis (HR 2.10, 1.07 to 4.16) were independent predictors of worse
survival (P < 0.001, P = 0.004 and P = 0.032 respectively). Eight of 61
asymptomatic patients with pNEN smaller than 2 cm had tumours graded G2 or G3,
and six of 51 patients had lymph node metastasis. Among patients with pNEC G3,
the presence of distant metastasis had a significant impact on the 5-year overall
survival rate: 0 per cent versus 43 per cent in those without distant metastasis
(P = 0.036). CONCLUSION: Neuroendocrine tumours graded G3, lymph node and distant
metastasis are independent predictors of worse overall survival in patients with
pNEN.
PMID- 25132003
TI - Integration of geriatric mental health screening into a primary care practice: a
patient satisfaction survey.
AB - OBJECTIVE: Colocation of mental health screening, assessment, and treatment in
primary care reduces stigma, improves access, and increases coordination of care
between mental health and primary care providers. However, little information
exists regarding older adults' attitudes about screening for mental health
problems in primary care. The objective of this study was to evaluate older
primary care patients' acceptance of and satisfaction with screening for
depression and anxiety. METHODS: The study was conducted at an urban,
academically affiliated primary care practice serving older adults. Study
patients (N = 107) were screened for depression/anxiety and underwent a post
screening survey/interview to assess their reactions to the screening experience.
RESULTS: Most patients (88.6%) found the length of the screening to be "just
right." A majority found the screening questions somewhat or very acceptable
(73.4%) and not at all difficult (81.9%). Most participants did not find the
questions stressful (84.9%) or intrusive (91.5%); and a majority were not at all
embarrassed (93.4%), upset (93.4%), or uncomfortable (88.8%) during the screening
process. When asked about frequency of screening, most patients (72.4%) desired
screening for depression/anxiety yearly or more. Of the 79 patients who had
spoken with their physicians about mental health during the visit, 89.8% reported
that it was easy or very easy to talk with their physicians about
depression/anxiety. Multivariate results showed that patients with higher anxiety
had a lower positive reaction to the screen when controlling for gender, age, and
patient-physician communication. CONCLUSIONS: These results demonstrate strong
patient support for depression and anxiety screening in primary care.
PMID- 25132006
TI - Mitochondrial DNA (mtDNA) variants in the European haplogroups HV, JT, and U do
not have a major role in schizophrenia.
AB - It has been reported that certain genetic factors involved in schizophrenia could
be located in the mitochondrial DNA (mtDNA). Therefore, we hypothesized that
mtDNA mutations and/or variants would be present in schizophrenia patients and
may be related to schizophrenia characteristics and mitochondrial function. This
study was performed in three steps: (1) identification of pathogenic mutations
and variants in 14 schizophrenia patients with an apparent maternal inheritance
of the disease by sequencing the entire mtDNA; (2) case-control association study
of 23 variants identified in step 1 (16 missense, 3 rRNA, and 4 tRNA variants) in
495 patients and 615 controls, and (3) analyses of the associated variants
according to the clinical, psychopathological, and neuropsychological
characteristics and according to the oxidative and enzymatic activities of the
mitochondrial respiratory chain. We did not identify pathogenic mtDNA mutations
in the 14 sequenced patients. Two known variants were nominally associated with
schizophrenia and were further studied. The MT-RNR2 1811A > G variant likely does
not play a major role in schizophrenia, as it was not associated with clinical,
psychopathological, or neuropsychological variables, and the MT-ATP6 9110T > C
p.Ile195Thr variant did not result in differences in the oxidative and enzymatic
functions of the mitochondrial respiratory chain. The patients with apparent
maternal inheritance of schizophrenia did not exhibit any mutations in their
mtDNA. The variants nominally associated with schizophrenia in the present study
were not related either to phenotypic characteristics or to mitochondrial
function. We did not find evidence pointing to a role for mtDNA sequence
variation in schizophrenia.
PMID- 25132007
TI - Strategic Provider Behavior Under Global Budget Payment with Price Adjustment in
Taiwan.
AB - Global budget payment is one of the most effective strategies for cost
containment, but its impacts on provider behavior have not been explored in
detail. This study examines the theoretical and empirical role of global budget
payment on provider behavior. The study proposes that global budget payment with
price adjustment is a form of common-pool resources. A two-product game theoretic
model is derived, and simulations demonstrate that hospitals are expected to
expand service volumes, with an emphasis on products with higher price-marginal
cost ratios. Next, the study examines the early effects of Taiwan's global budget
payment system using a difference-in-difference strategy and finds that Taiwanese
hospitals exhibited such behavior, where the pursuit of individual interests led
to an increase in treatment intensities. Furthermore, hospitals significantly
increased inpatient service volume for regional hospitals and medical centers. In
contrast, local hospitals, particularly for those without teaching status
designation, faced a negative impact on service volume, as larger hospitals were
better positioned to induce demand and pulled volume away from their smaller
counterparts through more profitable services and products such as radiology and
pharmaceuticals.
PMID- 25132008
TI - Malignant mesenchymoma with widespread metastasis including bone marrow
involvement in a dog.
AB - A male castrated Golden Retriever was presented for evaluation of a large mass
over the left shoulder extending to the lower part of the neck that had been
present for an extended period of time, but had a recent history of rapid growth.
Previous aspirates of the mass were consistent with a lipoma. The mass was
surgically excised and was diagnosed as an extraskeletal osteosarcoma based on
histopathology. After surgery, the dog was initiated on a chemotherapy protocol
with carboplatin and metronomic cyclophosphamide. He became neutropenic, anemic,
and thrombocytopenic 14 days after the carboplatin treatment was administered.
The neutropenia resolved, but the anemia and thrombocytopenia progressed. A bone
marrow aspirate revealed erythroid hypoplasia, myeloid hyperplasia with a
predominance of early precursors, and a subset of cells that made up 20% of the
total population that were reported as bizarre and unclassifiable. These cells
were discrete in nature and were thought to be hematopoietic in origin. The dog
was euthanized due to deterioration of the clinical condition. On postmortem
examination, widespread metastasis involving the lungs, liver, kidney, heart, and
bone marrow was found. Histopathology of the tumor lesions determined 2 distinct
malignant populations of liposarcoma and osteosarcoma, consistent with malignant
mesenchymoma. However, the possibility of 2 separate neoplastic processes cannot
be definitively excluded. This is the first report of bone marrow metastasis of a
malignant mesenchymoma in a dog.
PMID- 25132009
TI - Isolation and characterization of flagellar filament from zoospores of
Dermatophilus congolensis.
AB - Highly motile zoospores from Dermatophilus congolensis bovine isolates from
clinical dermatophilosis in Japan were obtained by culturing at 27 degrees C in
an ambient atmosphere on heart infusion agar supplemented with 5% defibrinated
sheep blood for 72h or in heart infusion broth for 48h with gentle shaking. After
vigorous mechanical agitation of the zoospore suspension, the flagellar filaments
detached from motile zoospores and were isolated in the clear gelatinous part of
the final pellet by differential centrifugation. Typical morphology of a
flagellar filament, with a width of approximately 15nm, was observed in the
isolated flagellar filament by electron microscopy. A single major protein
(flagellin) band with an apparent molecular mass of 35kDa was detected in the
flagellar filament of D. congolensis strain AM-1 and that of 33kDa was detected
in strain IT-2 by SDS-PAGE. In immunoblot analysis of whole-cell proteins from
seven isolates of D. congolensis, antiserum to strain AM-1 zoospores reacted with
the 35-kDa antigen band of strain AM-1, but not with any antigen band of other
strains in a similar molecular mass range. In contrast, antiserum to strain IT-2
zoospores reacted with antigen bands at 33kDa from six strains, except strain AM
1. Similar strain-specific reactions of these anti-zoospore sera with isolated
flagellar filaments from strains AM-1 and IT-2 were confirmed by immunoblot,
indicating the presence of antigenic variations of flagellins of D. congolensis
zoospores.
PMID- 25132010
TI - Skeletal effects of bariatric surgery: examining bone loss, potential mechanisms
and clinical relevance.
AB - Bariatric surgery is the most effective therapeutic approach to morbid obesity,
resulting in substantial weight loss and improved cardiometabolic profiles;
however, a growing body of evidence suggests that bariatric procedures increase
both skeletal fragility and the risk of related future fracture secondary to
excessive bone loss. Prospective evidence shows that areal bone mineral density
(BMD) assessed by dual energy X-ray absorptiometry (DXA) declines by as much as
14% in the proximal femoral regions, including the femoral neck and total hip, 12
months postoperatively. Lumbar spine areal BMD outcomes show greater 12-month
postoperative variability across surgical procedures (-8 to +6%) and contrast
with no change in volumetric BMD outcomes measured by quantitative computed
tomography. Diminished mechanical loading, micronutrient deficiency and
malabsorption, along with neurohormonal alterations, offer plausible underlying
mechanisms to explain these observed post-bariatric bone changes, but most remain
largely unsubstantiated in this population. Importantly, DXA-based skeletal
imaging may have limited utility in accurately detecting bone change in people
undergoing bariatric surgery; partly because excessive tissue overlying bone
increases the variability of areal BMD outcomes. Moreover, a paucity of fracture
and osteoporosis incidence data raises questions about whether marked post
bariatric surgery bone loss is clinically relevant or a functional adaptation to
skeletal unloading. Future studies that use technology which is able to
accurately capture the site-specific volumetric BMD and bone architectural
changes that underpin bone strength in people undergoing bariatric surgery, that
consider mechanical load, and that better quantify long-term fracture and
osteoporosis incidence are necessary to understand the actual skeletal effects of
bariatric surgery.
PMID- 25132011
TI - A proteomics-based methodology to investigate the protein corona effect for
targeted drug delivery.
AB - Here we introduce a proteomics methodology based on nanoliquid-chromatography
tandem mass spectrometry (nanoLC/MS-MS) to investigate the "protein corona effect
for targeted drug delivery", an innovative strategy, which exploits the "protein
corona" that forms around nanoparticles in a physiological environment to target
cells.
PMID- 25132012
TI - Quality of life and illness perception in primary biliary cirrhosis: a controlled
cross-sectional study.
AB - OBJECTIVE: The aim of this study was to understand better the quality of life
(QOL) and illness perception in women with primary biliary cirrhosis (PBC)
through a comparison with women having diabetes. METHODS: One hundred and ninety
four women took part in this study: 130 with PBC, 64 with type 2 diabetes. They
were administered the SF-12 to measure QOL and the Brief Illness Perception
Questionnaire to assess representations of their illness. Analysis of covariance
with bootstrapping was used to compare QOL and illness perception scores by
controlling age and mean disease duration. RESULTS: Physical QOL was
significantly worse for women with PBC than for women with diabetes. Women with
PBC felt their disease would last longer and reported more symptoms and concerns
related to their disease than women with diabetes. Significant differences were
also observed for causes: women with PBC mainly reported autoimmune, emotional,
unknown/unlucky and medical causes whereas women with diabetes reported mostly
lifestyle and hereditary causes. Marginally significant differences were observed
regarding consequences on daily life, feeling of control over the disease and
emotional responses, which were shown to be worse in PBC. Mental QOL, treatment
control and overall understanding of the disease was similar in both groups.
CONCLUSIONS: This study shows that women with PBC have a worse QOL and somewhat
different illness perception than women with diabetes. Further research could
help understand PBC specificities better in order to improve patient care,
especially if factors such as fatigue or rarity of the disease explain these
results.
PMID- 25132013
TI - Psoriasis and sport: a new ally?
AB - BACKGROUND: Psoriasis is a common chronic multifactorial disease which can result
in restrictions to social and recreational activities. Psoriasis subjects are at
high risk to develop metabolic and cardiovascular diseases. Physical activity, a
vital component in prevention and management of these diseases, is reported to be
potentially associated in a negative way with psoriasis. OBJECTIVE: To
investigate the relationship between psoriasis and physical activity. MATERIALS
AND METHODS: Anamnestic and physical examination as well as a specific doctor
administered questionnaire was performed to a group of 416 consecutive sportive
subjects and 489 sex and age-matched controls. Moreover, similar investigations
were executed on 400 consecutive psoriatic patients without psoriatic arthritis.
RESULTS: Psoriasis was significantly more common in controls respect to sportive
group (n = 27, 5.4% vs. n = 7, 1.7%, P < 0.01) whereas a positive familial
history of psoriasis was observed in similar percentages in both groups (n = 51,
10.2% vs. n = 40, 9.6%). The number of subjects performing sports activities was
significantly lower in psoriasis group compared to controls (n = 44, 11% vs. n =
106, 21.3%; P < 0.001). Of these psoriatic patients, 35/44 referred that sporting
activities showed a positive influence on the natural course of their disease,
whereas the remaining 11 patients did not highlight positive or negative
influences on their illness. Interestingly, 23.75% of psoriatic patients (n = 95)
related that they had regularly carried out sporting activities before the onset
of the dermatosis referring that psoriasis represented a huge obstacle to
continue practicing physical activities. CONCLUSION: Our survey showed that
regular physical activity may lower the risk of psoriasis and have a beneficial
effect on the natural course of the disease, positively influencing not only the
severity as well as the incidence of metabolic comorbidities, but also, through
possible epigenomic, metabolic, anti-inflammatory and psycho-emotional effects,
the onset of the dermatosis. However, larger birth cohort studies are needed to
confirm these results.
PMID- 25132014
TI - [Deaths in a Tunisian psychiatric hospital: an eleven-year retrospective study].
AB - BACKGROUND: Mortality in patients in psychiatric hospitals is reported to be two
to three times as high as in the general population. In Tunisia, we do not have
any figures on mortality and causes of death in psychiatric inpatients. AIM: The
aim of our study was to assess the mortality rate in a psychiatric hospital in
comparison to the mortality rate in the general population, to determine the
patients' profile, and to identify the causes and risk factors for these deaths.
METHODS: We performed a retrospective, descriptive and comparative study. We
examined the records of all patients who died during their stay in the different
wards of psychiatry at the Razi Hospital in Tunis. We also scrutinized reports of
autopsies in the Forensic Medicine unit at Charles-Nicolle Hospital in Tunis over
a period of eleven years from January 1st, 2000 to December 31st, 2010. We
conducted a descriptive study to calculate the standardized mortality ratio (SMR)
aiming to highlight any existing excess mortality among the psychiatric
inpatients compared to the general population. This ratio was obtained by
dividing the observed number of deaths by the expected number of deaths. In the
analytical study, our sample was compared to a control population made-up of
randomly selected living patients among those admitted to the Razi hospital in
2010. This study allowed us to investigate the risk factors for premature
mortality in psychiatric inpatients. RESULTS: The average rate of mortality was
two deaths per 1000 inpatients per year. Twenty-four percent (24%) of deaths
involved institutionalized patients. Compared to the general population,
premature mortality was noted among patients aged less than 40 (SMR=1.9). The
older the patients were, the closer to 1 the SMR was. The average age at death
was 51.38 years; 65% of patients were male, 60% had a low socio-economic level,
54% had a comorbid medical condition. Forty-two percent (42%) of deceased
patients were diagnosed with schizophrenia with the paranoid form being the most
prevalent (44%), 13% had bipolar disorder, 22% had psycho-organic disorders
(mental retardation, dementia, delirium). Antipsychotics were the most prescribed
psychotropic drugs. High doses were used. Forty percent of cases (40%) consisted
of sudden deaths. A cause for death was identified in 80% of cases. In 92% of
cases, the death was classified as being "natural". Main causes were respiratory
(26%) and cardiovascular (9%). Accidental causes accounted for 8% of deaths. In
20% of cases, the cause remained undetermined. Three factors were identified as
independent predictors of mortality among mental patients: age at death (OR=3.9
among patients older than 40), psychiatric diagnosis (OR=2.9 among patients with
psychotic or mood disorders compared to other diagnoses) and combination of
antipsychotic drugs (OR=6.09 in patients receiving more than two antipsychotics).
DISCUSSION: Young psychiatric inpatients seem to be at high risk of premature
death: the SMR in our study was 1.9. It ranged between 2.15 and 6.55 in other
similar studies. This increased risk mainly concerns non-natural deaths. The
leading natural cause of death in our population was represented by
thromboembolic accidents. Such a high thromboembolic risk may be explained by the
mental illness itself, by physical restraint as well as by antipsychotic
treatment. Diagnosing medical conditions in psychiatric patients is often a
daunting task: history of the patient is sometimes unreliable and clinical
features might be modified by psychotropic agents. Patient-related risk factors
for premature death include poor socio-economic level, access-to-care
difficulties, positive family and personal history of mental and/or medical
disorders, smoking, substance abuse, unhealthy diet and lack of physical
activity. Moreover, iatrogenic effects of psychotropic drugs (combination of
antipsychotics was more common in deceased patients than in controls) and
inadequate medical care in psychiatric hospitals (lack of ECG devices, in
particular) partly account for such a high mortality. CONCLUSION: Identifying
risk factors for deaths in psychiatric hospitals highlights needed changes in
psychiatric management strategies taking into account the patient's
characteristics as well as the drugs' safety profile. Further studies with larger
samples are needed to better highlight risk factors for premature death in
psychiatric inpatients. Identifying such risk factors is necessary to develop
efficient preventive strategies.
PMID- 25132015
TI - [An integrative and transdiagnostic relaxation protocol for anxious patients.
Results of a pilot study].
AB - INTRODUCTION: The literature data show that relaxation practice is effective in
reducing anxiety symptoms. Different techniques such as progressive muscular
relaxation, autogenic training, applied relaxation and meditation have been
evaluated independently for anxiety disorders. The question is to know whether
the combination of various techniques may be of interest in the transdiagnostic
treatment of anxiety disorders. AIM OF THE STUDY: The present study assessed the
short-term efficacy of a 10-week integrative and transdiagnostic relaxation
program for anxiety disorders in outpatients of an anxiety disorders unit.
METHODS: The diagnoses were made according to the Mini-International
Neuropsychiatric Interview (MINI; Sheehan et al., 1998) and completed with an
assessment of anxiety and depressive symptoms using: the State Trait Anxiety
Inventory (STAI-Y, -S and -T), the Penn State Worry Questionnaire (PSWQ) and the
Beck Depression Inventory (BDI-II). Four techniques were integrated into the
structured 10-week protocol: breathing control, muscular relaxation, meditation
and mental visualization. RESULTS: Twenty-eight patients (12 men and 16 women),
mean age (S.D.)=38.82 years (11.57), were included in the study. All the included
patients fulfilled the DSM-IV criteria for a current diagnosis of Generalized
Anxiety Disorder (n=13) or Panic Disorder (n=15) with or without agoraphobia. At
the end of the 10 sessions, we found a significant reduction in mean scores
(S.D.) on the STAI-T from 53.179 (6.037) to 49.821 (8.028) (P<0.02), the BDI-II
20.964 (13.167) to 15.429 (11.341) (d=0.6543) and the QIPS 55.071 (10.677) to
49.679 (11.7) (d=0.5938). The observed reduction in the STAI-S (d=0.2776) was not
significant. DISCUSSION: The results of this open study showed that this program
significantly decreases the level of trait anxiety, depression and worry. The
integrative and transdiagnostic relaxation program could represent an accessible
and effective treatment to reduce anxious and depressive symptoms in various
anxiety disorders. Future research should address the development of controlled
trials assessing the impact of the different dimensions of anxiety and the long
term effects of this protocol.
PMID- 25132016
TI - Clinical and molecular characteristics of community-acquired methicillin
resistant Staphylococcus aureus infections in Chinese neonates.
AB - This study aims to characterize the clinical features of community-acquired
methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in Chinese
neonates, as well as the molecular characteristics and expression of key
virulence genes of isolates. Clinical information and molecular characteristics
of 130 cases were analyzed. Up to 83.8% patients were affected with late-onset
infection. Cesarean delivery was the main delivery route, accounting for 74.6% of
the total deliveries. Pneumonia (69, 53.1%) was the most common infection. A
total of 38 patients (29.2%) suffered from complications. Moreover, 35 cases
(26.9%) were invasive infections, among which 88.6% involved multiple organs and
45.7% suffered from complications. Cesarean section and premature birth were the
risk factors for invasive CA-MRSA infection. ST59-MRSA-SCCmecIVa-t437 (54, 41.5%)
was the most predominant CA-MRSA clone. The hla expression in the ST59 isolates
was higher than that in ST910 (p = 0.02) and the hla expression in ST59-SCCmecV
t437 was higher than that in ST59-SCCmecIVa-t437. Approximately, 46.4% (13/28) of
the infections caused by ST59-SCCmecV were invasive. This value is higher than
that of ST59-SCCmecVa caused infections (14/59, 23.7%) (p = 0.03). This study
showed that neonatal CA-MRSA infections in China readily become invasive, involve
multiple organs, and are often accompanied by complications. The SCCmec V clone
may be more pathogenic than the SCCmecVIa clone.
PMID- 25132017
TI - The rtA181S mutation of hepatitis B virus primarily confers resistance to
adefovir dipivoxil.
AB - The study aimed to clarify clinical significance of hepatitis B virus (HBV)
rtA181S mutation in Chinese HBV-infected patients. A total of 18 419 patients
with chronic HBV infection from Beijing 302 Hospital were investigated. HBV
complete reverse transcriptase region of polymerase was screened by direct
sequencing, and the results were verified by clonal sequencing. Replication
competent mutant and wild-type HBV genomic amplicons were constructed and
transfected into the HepG2 cells and cultured in the presence or absence of
serially diluted nucleos(t)ide analogues. Intracellular HBV replicative
intermediates were quantitated for calculating the 50% effective concentration of
the drug (EC(50)). The rtA181S was detected in 98 patients with 12 kinds of
mutational patterns. Genotype C and genotype B HBV infection occupied 91.8% and
8.2% in rtA181S-positive patients, in contrast to 84.6% and 15.4% in rtA181S
negative patients (P < 0.01). All rtA181S-positive patients had received
nucleos(t)ide analogues. rtA181S was detected in multiple patients with virologic
breakthrough. Phenotypic analysis of patient-derived viral strains showed that
rtA181S, rtA181S+N236T, rtN236T and rtA181V strains had 68.5%, 49.9%, 71.4% and
66.2% of natural replication capacity of wild-type strain, and 3.7-fold, 9.8
fold, 7.9-fold and 5.6-fold increased EC(50) to adefovir dipivoxil (ADV). The
rtA181S strain remained susceptible to lamivudine, entecavir and tenofovir, and
ADV susceptibility was restored after the mutation was eliminated through site
directed mutagenesis. Rescue therapy with entecavir or combination therapy was
effective in rtA181S-related ADV-refractory patients. The rtA181S mutation
confers moderate resistance to ADV. It could be induced by either lamivudine or
ADV and contribute ADV treatment failure.
PMID- 25132019
TI - Spatiotemporal properties of auditory intensity processing in multisensor MEG.
AB - Loudness dependence of auditory evoked potentials (LDAEP) evaluates loudness
processing in the human auditory system and is often altered in patients with
psychiatric disorders. Previous research has suggested that this measure may be
used as an indicator of the central serotonergic system through the highly
serotonergic innervation of the auditory cortex. However, differences among the
commonly used analysis approaches (such as source analysis and single electrode
estimation) may lead to different results. Putatively due to discrepancies of the
underlying structures being measured. Therefore, it is important to learn more
about how and where in the brain loudness variation is processed. We conducted a
detailed investigation of the LDAEP generators and their temporal dynamics by
means of multichannel magnetoencephalography (MEG). Evoked responses to brief
tones of five different intensities were recorded from 19 healthy participants.
We used magnetic field tomography in order to appropriately localize superficial
as well as deep source generators of which we conducted a time series analysis.
The results showed that apart from the auditory cortex other cortical sources
exhibited activation during the N1/P2 time window. Analysis of time courses in
the regions of interest revealed a sequential cortical activation from primary
sensory areas, particularly the auditory and somatosensory cortex to posterior
cingulate cortex (PCC) and to premotor cortex (PMC). The additional activation
within the PCC and PMC has implications on the analysis approaches used in LDAEP
research.
PMID- 25132018
TI - Diagnostic accuracy of C-reactive protein and procalcitonin in the early
detection of infection after elective colorectal surgery - a pilot study.
AB - BACKGROUND: Colorectal surgery is associated with postoperative infectious
complications in up to 40% of cases, but the diagnosis of these complications is
frequently misleading, delaying its resolution. Several biomarkers have been
shown to be useful in infection diagnosis. METHODS: We conducted a single-centre,
prospective, observational study segregating patients submitted to elective
colorectal surgery with primary anastomosis, CRP and PCT were measured daily. We
compared infected and non-infected patients. RESULTS: From October 2009 to June
2011, a total of 50 patients were included. Twenty-one patients developed
infection. PCT and CRP before surgery were equally low in patients with or
without postoperative infectious complications. After surgery, both PCT and CRP
increased markedly. CRP time-course from the day of surgery onwards was
significantly different in infected and non-infected patients (P = 0.001)
whereas, PCT time-course was almost parallel in both groups (P = 0.866). Multiple
comparisons between infected and non-infected patients from 5th to 9th
postoperative days (POD) were performed and CRP concentration was significantly
different (P < 0.01, Bonferroni correction), on the 6th, 7th and 8th POD. A CRP
concentration > 5.0 mg/dl at the D6 was predictive of infection with a
sensitivity of 85% and a specificity of 62% (positive likelihood ratio 2.2,
negative likelihood ratio 0.2). CONCLUSIONS: After a major elective surgical
insult both CRP and PCT serum levels increased independently of the presence of
infection. Besides serum CRP time-course showed to be useful in the early
detection of an infectious complication whereas PCT was unhelpful.
PMID- 25132022
TI - [Measures of preventing occupational exposure to hazardous drugs-based on new
insights].
AB - Little attention has been paid to the hazards that healthcare professionals may
be exposed to when administering drugs to patients. Hazardous drugs, even in very
low concentrations, can produce adverse reactions in patients and in healthcare
professionals who handle the drugs or work in the vicinity. Small amounts of
hazardous drugs have been detected in the urine of healthcare professionals who
prepare or administer these drugs even with the use of safety protection.
Moreover, environmental contamination of hazardous drugs has been reported in a
survey of patient care surroundings even when handling guidelines have been
followed. The academic subcommittee of the Japanese Society of Hospital Pharmacy
has established guidelines for the handling of hazardous drugs; however, reports
suggest that there are problems with compliance to the guidelines. Recently,
closed system devices have been marketed for use in healthcare settings to reduce
environmental contamination during drug preparation. However, these devices have
not gained widespread use because of their high cost and incompatibility with
certain products like ampules. In addition, it is not clear whether the hazardous
drugs are deactivated by these devices. In an effort to prevent healthcare
professionals from being exposed to hazardous drugs, it is important to clean up
contaminated surfaces and also to prevent dangerous drugs from spreading.
PMID- 25132020
TI - Face processing regions are sensitive to distinct aspects of temporal sequence in
facial dynamics.
AB - Facial movement conveys important information for social interactions, yet its
neural processing is poorly understood. Computational models propose that shape-
and temporal sequence sensitive mechanisms interact in processing dynamic faces.
While face processing regions are known to respond to facial movement, their
sensitivity to particular temporal sequences has barely been studied. Here we
used fMRI to examine the sensitivity of human face-processing regions to two
aspects of directionality in facial movement trajectories. We presented genuine
movie recordings of increasing and decreasing fear expressions, each of which
were played in natural or reversed frame order. This two-by-two factorial design
matched low-level visual properties, static content and motion energy within each
factor, emotion-direction (increasing or decreasing emotion) and timeline
(natural versus artificial). The results showed sensitivity for emotion-direction
in FFA, which was timeline-dependent as it only occurred within the natural frame
order, and sensitivity to timeline in the STS, which was emotion-direction
dependent as it only occurred for decreased fear. The occipital face area (OFA)
was sensitive to the factor timeline. These findings reveal interacting temporal
sequence sensitive mechanisms that are responsive to both ecological meaning and
to prototypical unfolding of facial dynamics. These mechanisms are temporally
directional, provide socially relevant information regarding emotional state or
naturalness of behavior, and agree with predictions from modeling and predictive
coding theory.
PMID- 25132023
TI - [Maintenance therapy for advanced non-small-cell lung cancer].
AB - Maintenance therapy is a new treatment strategy for advanced non-small-cell lung
cancer(NSCLC), and it consists of switch maintenance and continuation
maintenance.Switch maintenance is the introduction of a different drug, not
included as part of the induction therapy, immediately after completion of 4
cycles of first-line platinum-based chemotherapy.Continuation maintenance is a
continuation of at least one of the drugs used in the induction therapy in the
absence of disease progression.Several phase III trials have reported survival
benefits with continuation maintenance of pemetrexed and switch maintenance of
pemetrexed or erlotinib.Therefore, maintenance therapy has become a part of the
standard first-line treatment for advanced NSCLC.However, further research is
needed to elucidate the selection criteria of patients who may benefit the most
from maintenance therapy.
PMID- 25132024
TI - [Maintenance therapy for colorectal cancer].
AB - Some trials have demonstrated the benefits of maintenance chemotherapy for
advanced colorectal cancer. In chemotherapeutic strategies for advanced
colorectal cancer, chemotherapy-related toxicity prevention and quality of
life(QOL)maintenance are more important than the introduction of a strong
regimen, especially when additional surgery is not possible. In Japan, the
combination of a folinic acid/5-fluorouracil/oxaliplatin(FOLFOX)regimen and
bevacizumab is a popular first-line chemotherapy regimen. However, despite its
effectiveness, neuropathy or hand-foot syndrome after 5 or 6 cycles tends to lead
to chemotherapy withdrawal. CAIRO3 trial reported the effectiveness of
capecitabine and bevacizumab as a maintenance chemotherapy regimen. Additionally,
the ML18147 trial demonstrated that bevacizumab beyond progression(BBP)prolonged
overall survival(OS)and progression free survival(PFS)in patients with advanced
colorectal cancer. Although those trials demonstrated the effectiveness of
continuous or maintenance bevacizumab administration, no trials have compared the
effectiveness of cytotoxic drugs with bevacizumab as maintenance therapies.
Moreover, controversy exists regarding the selection of drugs as a maintenance
therapy and the identification of patients who would benefit from maintenance
therapy.
PMID- 25132021
TI - Heritability of head motion during resting state functional MRI in 462 healthy
twins.
AB - Head motion (HM) is a critical confounding factor in functional MRI. Here we
investigate whether HM during resting state functional MRI (RS-fMRI) is
influenced by genetic factors in a sample of 462 twins (65% female; 101 MZ
(monozygotic) and 130 DZ (dizygotic) twin pairs; mean age: 21 (SD = 3.16), range
16-29). Heritability estimates for three HM components-mean translation (MT),
maximum translation (MAXT) and mean rotation (MR)-ranged from 37 to 51%. We
detected a significant common genetic influence on HM variability, with about two
thirds (genetic correlations range 0.76-1.00) of the variance shared between MR,
MT and MAXT. A composite metric (HM-PC1), which aggregated these three, was also
moderately heritable (h(2) = 42%). Using a sub-sample (N = 35) of the twins we
confirmed that mean and maximum translational and rotational motions were
consistent "traits" over repeated scans (r = 0.53-0.59); reliability was even
higher for the composite metric (r = 0.66). In addition, phenotypic and cross
trait cross-twin correlations between HM and resting state functional
connectivities (RS-FCs) with Brodmann areas (BA) 44 and 45, in which RS-FCs were
found to be moderately heritable (BA44: h(2) = 0.23 (sd = 0.041), BA45: h(2) =
0.26 (sd = 0.061)), indicated that HM might not represent a major bias in genetic
studies using FCs. Even so, the HM effect on FC was not completely eliminated
after regression. HM may be a valuable endophenotype whose relationship with
brain disorders remains to be elucidated.
PMID- 25132025
TI - [Maintenance therapy in patients with advanced epithelial ovarian cancer-impact
of anti-angiogenic molecular targeted agents in progress].
AB - However, in patients with epithelial ovarian cancer, the standard chemotherapy of
paclitaxel/carboplatin (TC) therapy is very effective as the overall survival
(OS) reached 70-80% in early stage (stage I/II ) patients, in advanced stage
patients like stage III/IV the recurrence rate exceeds 80%and the 5-year-OS
remains 55%at most. Longer survival remains so worse as well that the 10-year-OS
fails to 5-7%. In order to push up the rate of longer survival, the strategies
have been considered from the some points of view such as additional new anti
cancer agents, changing of drug delivery system (DDS) (i.e. intraperitoneal
administration), additional radiotherapy or radioactive agents (in USA), the
combination of molecular agents and specific classification in treatment using
"Bio-markers (so-called tailor-made medicine)". Here we reviewed the up-coming
treatments in maintenance fashion using anti-angiogenic agents or supposing
effective and curable treatment by PARP inhibitors in the cohorts of epithelial
ovarian cancers with BRCAness.
PMID- 25132026
TI - [Current status of adjuvant chemotherapy in patients with p-Stage II and p-Stage
III gastric cancer].
AB - The results of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer(ACTS
GC)demonstrated that postoperative chemotherapy using S-1 is a standard treatment
in Japan for patients with p-Stage II and p-Stage III gastric cancer. We
retrospectively reviewed the effect of adjuvant chemotherapy received by 47
patients with p-Stage II and p-Stage III gastric cancer between January 2007 and
June 2012. Our hospital is a local university hospital with a high intensive care
unit. S-1 monotherapy was administered to 32 patients(adjuvant S-1 group, 68.1%);
22 patients(68.8%)among them completed one year of therapy without any
modification to the administration schedule. A total of 8
patients(25.0%)experienced grade 3 adverse events, and 9 patients required a dose
reduction, a modification of the administration schedule, or termination of the
therapy. S-1 was not administrated to 15 patients(no adjuvant S-1 group, 31.9%);
among these patients, 12(80.0%) were not administered S-1 because of their
advanced age and comorbidity. The 3-year overall survival rate was 89.3% in the
adjuvant S-1 group and 77.1% in the no adjuvant S-1 group. The completion rate of
S-1 and survival rate were high for patients in the adjuvant S-1 group, which was
similar to the results of the ACTS-GC. However, 25 of 47 patients(53.2%) with p
Stage II and p-Stage III gastric cancer did not improve after sufficient adjuvant
therapy; therefore, it is important to develop new treatment strategies for these
patients.
PMID- 25132027
TI - Efficacy of high-dose toremifene therapy in postmenopausal patients with
metastatic breast cancer resistant to aromatase inhibitors:a retrospective,
single-institution study.
AB - BACKGROUND: Aromatase inhibitors(AI)have established efficacy as first-line
therapy in postmenopausal patients with hormone-sensitive metastatic breast
cancer(MBC). However,the use of endocrine therapy has not yet been established
for second-line and later therapy. Our study examined the efficacy of high-dose
toremifene therapy(HD-TOR)in patients with MBC resistant to AIs. PATIENTS AND
METHODS: A retrospective analysis was carried out to determine outcomes in 85
postmenopausal patients with MBC resistant to AIs who began HD-TOR between May
2001 and October 2011. The patients received toremifene 120 mg once daily on
consecutive days. RESULTS: The objective response rate(ORR)was 21.2%,the clinical
benefit rate(CBR)was 41.2%,and the median time to treatment failure(TTF)was 7.3
months. The CBR was high in patients with ER-positive status(p=0.045),no visceral
metastasis(p=0.037),HD -TOR as first- or second-line therapy(p=0.007),no history
of tamoxifen(TAM)therapy(p=0.019),and no history of chemotherapy(p=0.017).
Multivariate analysis showed that ER-positive status(p=0.005, odds ratio:
0.064)and no visceral metastasis(p=0.034, odds ratio: 0.323)were independent
predictors of efficacy. The TTF was significantly longer in patients with ER
positive status(p=0.019)and no history of TAM therapy(p=0.015). Multivariate
analysis showed that ER-positive status(p=0.025, hazard ratio: 0.377)and no
history of TAM therapy(p=0.002, hazard ratio: 0.422)were independent predictors
of efficacy. No patient discontinued HDTOR therapy due to adverse events.
CONCLUSION: HD-TOR is an effective endocrine therapy for patients with MBC who
have failed AIs.
PMID- 25132028
TI - [Examination of a relapsing pattern of cases of completely resected non-small
cell lung cancer].
AB - PURPOSE: The purpose of this research was to understand the clinical discovery of
a relapse, relapse time, and the presentation of the first relapse of non-small
cell lung cancer(NSCLC)by examining cases of relapse after complete resection of
NSCLC. Objective and method. Cases of relapse after complete resection of NSCLC
in our hospital were examined. RESULTS: Fifteen cases were evaluated. In half of
these cases, relapse was discovered owing to increased tumor marker values. Of
the patients, 60%had a relapse within 2 years after resection and 20%had a
relapse 5 years after resection. The first relapse was a local recurrence in 9
cases, lung metastasis in 5 cases, and distant metastasis outside the thoracic
cavity in 3 cases. CONCLUSION: The effectiveness of the tumor marker as a
diagnostic parameter of relapse in NSCLC was demonstrated. Discovering distant
metastases at the early postoperative period and relapse 5 years after resection
are important.
PMID- 25132029
TI - [Analysis of factors influencing the occurrence of infusion reaction after
initial treatment with rituximab].
AB - We investigated factors influencing the occurrence of infusion reactions after
initial treatment with rituximab. We included patients who were administered
rituximab for the treatment of B-cell non-Hodgkin's lymphoma at the Gifu
Municipal Hospital Hematology from February 2010 to March 2013. Fifty-one
patients were included; their median age was 72(44-87)years, and 31 were men and
20 were women. We defined the index of infusion reaction as the maximal change in
body temperature within 24 hours from the administration of rituximab and
evaluated the correlation with change in body temperature and each factor, and
differences of change in body temperature between the upper and lower groups
divided by standard value of each factor by using the t test without
correspondence. The "2,000 U/mL or less group"of soluble interleukin-2
receptor(sIL- 2R)levels and the "over 2,000 U/mL group"showed significant
different(p=0.014). The "double value or less group"of a standard value(211
IU/L)and "over double value group"showed significantly different lactate
dehydrogenase(LDH)levels (p=0.017). The "lower limit or less group"of the
standard value(men: 13 g/dL, women: 12 g/dL)and the "over lower limit
group"showed significantly different hemoglobin(Hb)levels(p=0.020). In
conclusion, the levels of sIL-2R, LDH, and Hb may predict the occurrence of
infusion reaction after the initial administration of rituximab in patients with
B-cell non-Hodgkin's lymphoma.
PMID- 25132030
TI - [Subcutaneous implantation type central venous port management in patients with
malignant tumors effect of different antiseptic agents on central venous port
related infection].
AB - Subcutaneous implantation type central venous ports(CV ports)are used in
chemotherapy. Here, we prospectively examined the frequency of CV port-related
infections when the disinfectant was changed from 10% povidone iodine to 1%
chlorhexidine ethanol or 70% ethanol. The subjects were patients with malignant
tumors, who had newly been implanted with CV ports. We examined CV port-related
infections at 1 week after CV port implantation and every 2 weeks thereafter,
following sterilization upon insertion of a Huber needle to the CV port. CV port
evulsion due to CV port-related infection was noted in 3 patients(4.8%)in whom
15%chlorhexidine ethanol was used(n=62)and in 2 patients(3.3%)in whom 70% ethanol
was used(n=60). Infection rates per 1,000 days of CV port use were 1.48% and
1.01%, respectively. Thus, the outcomes of sterilization using 1% chlorhexidine
ethanol and 70% ethanol did not differ significantly from those on using 10%
povidone iodine for sterilization, based on preliminary results at our
institution(3 of 59 patients[5.1%]had port evulsion due to CV port-related
infection and the infection rate per 1,000 days of CV port use was 1.47%, Akahane
et al, 2012). Chlorhexidine ethanol and ethanol are very convenient to use
because they dry quickly and do not need discoloration. Accordingly,
chlorhexidine ethanol and ethanol might be useful in CV port management.
PMID- 25132031
TI - [Relation between pain and health-related quality of life in cancer patients].
AB - PURPOSE: This study aimed to investigate the relation between pain and health
related quality of lif e(HRQOL)in cancer patients. METHODS: An internet-based
HRQOL survey of 618 patients with different malignancies using the EORTC QLQ-C30
and BPI-SF was performed. Three study groups were formed based on the pain in the
previous month: group A comprised patients without pain; group B comprised
patients with mild pain; and group C comprised patients with moderate to severe
pain. RESULTS: Compared with both groups A and B, group C had significantly low
global HRQOL and functioning, which resulted in fatigue, dyspnea, disturbed
sleep, and financial difficulties. In addition, the patients in group C were
significantly dissatisfied with their cancer medical service compared with the
patients in both groups A and B. CONCLUSION: Pain is an important health issue
that not only negatively affects the HRQOL but also results in fatigue, dyspnea,
disturbed sleep, and financial difficulties in cancer patients. These symptoms
may be important key words for HRQOL analysis in clinician-patient interviews.
PMID- 25132032
TI - [A case of malignant peritoneal mesothelioma diagnosed with laparoscopic biopsy].
AB - A 66-year-old woman was admitted to our hospital for massive ascites of unknown
origin. Peritoneal mesothelioma was suspected because of her history of asbestos
exposure. Diagnostic laparoscopy with biopsy of the peritoneum and greater
omentum was performed. Pathological examination with immunostaining provided a
definite diagnosis of malignant peritoneal mesothelioma. The patient underwent
early postoperative induction therapy with pemetrexed and carboplatin, which
resulted in a reduction in ascites. Laparoscopic biopsy contributed to the
definite diagnosis of malignant peritoneal mesothelioma, and thereby, early
induction of chemotherapy.
PMID- 25132033
TI - [A case of syndrome of inappropriate antidiuretic hormone secretion in a patient
with esophageal carcinoma possibly induced by cisplatin in neoadjuvant
chemotherapy].
AB - A 60 -year-old man complained of dysphagia and was admitted to our hospital for
adjuvant chemotherapy under a diagnosis of esophageal carcinoma(squamous cell
carcinoma[SCC], Stage II ). He was treated with cisplatin(CDDP)and 5-
fluorouracil(5-FU). On the fifth day after administration, he experienced mild
disorientation, and early morning on the sixth day, he showed impaired
consciousness. Laboratory studies revealed a serum sodium level of 111mEq/L and a
serum chloride level of 73mEq/L. The findings of computed tomography and magnetic
resonance imaging of the head were unremarkable. Other laboratory studies
revealed a plasma vasopressin level of 19.2 pg/mL, a plasma osmolality of
219mOsm/kg, a serum creatinine level of 0.61mg/dL, a serum cortisol level of 27.1
mg/dL, a urine osmolality of 665mOsm/kg, and a urine sodium level of 157.1mEq/L.
There were no signs of dehydration, and so the patient was diagnosed with
syndrome of inappropriate antidiuretic hormone secretion(SIADH). We discontinued
chemotherapy and initiated fluid restriction and sodium supplementation. After
this treatment, the patient's consciousness progressively improved. On the fifth
day of treatment, laboratory studies revealed a serum sodium level of 138mEq/L
and a serum chloride level of 98mEq/L, indicating recovery from hyponatremia.
PMID- 25132034
TI - [A case of gastric cancer with N2 lymph node metastasis and pancreatic invasion
effectively treated with docetax-el/S-1 as a neoadjuvant chemotherapy].
AB - A 74-year-old man was diagnosed with advanced gastric cancer(cStage III B).
Laparotomy showed N2 lymph node metastasis and pancreatic invasion. Radical
resection appeared impossible and was thus not performed. Chemotherapy consisting
of a combination of S-1(80mg/m 2, 2-week administration and 1-week rest), and
docetaxel(40mg/m2day 1)was administered with the expectation of tumor
downstaging. A partial response(PR)was obtained after five courses of this
regimen in which the primary lesion and lymph node swelling remarkably improved.
Total gastrectomy, splenectomy, partial colectomy, and D2 lymph node dissection
were then performed. Pathological analysis revealed very few cancer cells in the
primary lesion and that the lymph nodes had become scarred and fibrotic. The
histological appearance was judged to be grade 2 and the final diagnosis was
T1N0H0P0CY0M0, fStage I A, curability A. Currently, more than 6 years and 4
months after the operation, the patient is alive without any evidence of
recurrence. Thus, docetaxel/S-1 combination therapy was an effective neoadjuvant
chemotherapy for this case of advanced gastric cancer.
PMID- 25132035
TI - [A case of advanced gastric cancer with multiple liver metastases treated with
preoperative TS-1/CDDP chemotherapy and resection, with a complete response and
survival for 7 years].
AB - CASE: An 82-year-old man died because of squamous cell carcinoma of the right
lung with metastasis to the left femoral bone. At the age of 75 years, he was
admitted to our hospital because of hematemesis. Widespread type 3 gastric cancer
was detected in the lesser curvature. Computed tomography(CT)showed multiple
liver metastases. Preoperative chemotherapy with TS-1/cisplatin(CDDP)was
administered. TS-1 was orally administered at 80mg/body/day and CDDP was
administered by intravenous infusion at 20mg/body/day every week for 3 weeks and
this was followed by a drug-free 2-week period as the first course. After the
fourth course, gastrectomy was performed for the primary lesion and
radiofrequency ablation(RFA)was performed for the liver metastases. The patient
survived for more than 7 years with a complete response (CR)and died thereafter
because of squamous cell carcinoma of the lung.
PMID- 25132036
TI - [A case of disseminated carcinomatosis of the bone marrow with disseminated
intravascular coagulation caused by advanced colon cancer successfully treated
with SOX/bevacizumab].
AB - Our patient was a 58-year-old man who was diagnosed with a large bowel
obstruction caused by ascending colon cancer, together with multiple liver
metastases for which a right hemicolectomy was performed. After the operation, he
developed disseminated intravascular coagulation(DIC)and severe anemia. Bone
marrow biopsy findings led to a diagnosis of disseminated carcinomatosis of the
bone marrow caused by colon cancer. We administered S-1+oxaliplatin(SOX) and
bevacizumab( BV)chemotherapy, which improved the DIC. The patient was discharged
from the hospital. After a total of six courses of chemotherapy, the carcinoma
became resistant. We changed the drug regimen and his clinical condition
improved. He survived for 292 days from the onset of disease.
PMID- 25132037
TI - [A case of a patient with advanced rectal cancer and urinary bladder fistula
surviving for 6 years after chemoradiotherapy without surgery].
AB - A 60-year-old man with advanced rectal cancer and urinary bladder fistula
received preoperative chemoradiotherapy with S-1(120mg/m / 2day)on weekdays and
concurrent radiotherapy(65 Gy). After chemoradiotherapy, the clinical symptoms
resolved and the tumor shrunk, as observed on endoscopic and radiologic
examinations. However, remnant cancer was suspected; therefore, modified
oxaliplatin, 5-fluorouracil, and Leucovorin(mFOLFOX6)therapy was initiated,
although it was stopped after 3 cycles because of numbness in the lower
extremities. Finally, clinical and pathological complete response(CR) was
achieved by administering additional doses of S-1 for approximately 1 year after
treatment initiation; CR was confirmed by using endoscopy and computed
tomography(CT), and there has been no recurrence for 6 years. This case suggests
that treatment without surgery is a viable alternative for advanced rectal cancer
with pathological CR after chemoradiotherapy.
PMID- 25132038
TI - [Gallbladder cancer with elevated serum alpha-fetoprotein, alpha-fetoprotein-L3,
and human chorionic gonadotropin levels].
AB - A 61-year-old woman presented with fever and was diagnosed with
choledocholithiasis, which was removed endoscopically. Incidentally, a markedly
elevated serum alpha-fetoprotein(AFP)level was detected(1,951 ng/mL), but
computed tomography( CT)showed only diffuse gallbladder wall thickening.
Subsequently, markedly elevated serum AFP-L3 and human chorionic
gonadotropin(HCG)levels were detected(99.6%and 2,867mIU/mL, respectively).
Fluorodeoxyglucose(FDG)- positron emission tomography/CT demonstrated high FDG
uptake only in the gallbladder. Gallbladder cancer was suspected and the patient
was scheduled for a cholecystectomy. However, CT just prior to surgery revealed
multiple liver metastases. Percutaneous gallbladder biopsy revealed a moderately
differentiated adenocarcinoma positive for AFP but not HCG. The patient underwent
chemotherapy consisting of gemcitabine and cisplatin. A CT scan obtained 12 weeks
later showed disease progression and AFP and HCG levels were found to have
increased to 4,021 ng/mL and 66,000mIU/mL, respectively. Although
immunohistochemistry of biopsy specimen did not demonstrate HCG production,
increased serum HCG level on disease progression definitely suggested HCG
production of gallbladder cancer. We believe the biopsy specimen was very small
and therefore did not prove HCG production. Gallbladder cancer with simultaneous
production of AFP and HCG is rare, and we therefore report this case together
with a review of the literature.
PMID- 25132039
TI - [A case of locally advanced and metastatic breast cancer successfully treated
with combination therapy of paclitaxel and bevacizumab].
AB - The patient was a 53-year-old woman with a large left breast tumor. Triple
negative breast cancer with bilateral axillary lymph-node metastasis and bone
metastasis was diagnosed. The primary treatment consisted of chemotherapy with a
combination of paclitaxel(PTX 80mg/m 2)and bevacizumab(Bev 10 mg/kg). After
chemotherapy, the tumor shrunk and showed an obvious decrease in size, eventually
disappearing. After therapy, an ulcer was detected on the left breast, and
mastectomy and axillary lymph node dissection were performed. The patient's
postoperative course was uneventful and she has been receiving chemotherapy at
our outpatient clinic. Thus, combination therapy with PTX and Bev may be useful
for the local control of advanced breast cancer.
PMID- 25132040
TI - [A case and literature review of ovarian carcinosarcoma with long-term survival
after repeated recurrences].
AB - Ovarian carcinosarcoma is a rare and aggressive tumor with a poor prognosis. We
report a case of ovarian carcinosarcoma and also review the literature. In 2000,
a 63-year-old woman underwent optimal cytoreductive surgery for ovarian
carcinosarcoma( International Federation of Gynaecology and Obstetrics[FIGO]stage
III c[pT3cN0M0]). She received adjuvant chemotherapy with paclitaxel and
carboplatin(TC). In 2005, a recurrent tumor was noted anterior to the sacrum. The
patient had a complete response after 6 cycles of TC chemotherapy; however, a
year later, the tumor recurred and was resected. In 2013, the tumor recurred
adjacent to the right kidney and was surgically removed after a partial response
to 3 cycles of TC chemotherapy. The pathologic findings included epithelial and
non-epithelial components with histologic variation and differentiation;
specifically, a leiomyosarcoma, cartilaginous tissues with cellular atypia, and a
rhabdomyosarcoma were identified in specimens obtained during the first, second,
and third surgical procedures, respectively. In keeping with the combination
theory of histogenesis, the ovarian carcinosarcoma described herein may have
originated from a monoclonal stem cell. The long survival of this patient is
attributed to optimal cytoreduction during the primary operation, solitary
recurrent tumors that were completely resected, and sensitivity to chemotherapy.
PMID- 25132041
TI - [A case of a large liposarcoma of the chest].
AB - A49 -year-old woman with a growing tumor of the left anterior chest wall was
admitted to our hospital. This patient was diagnosed with a malignant well
differentiated tumor by needle biopsy and underwent surgery involving wide
resection of the tumor, associated excision of the major pectoralis muscle, and
part of the mammary tissue and skin. The tumor measured 14.2*17.8 cm and weighed
1,220 g. Histopathologically, the tumor was confirmed to be a dedifferentiated
liposarcoma, and local recurrence and metastasis often occurs in spite of
complete surgical resection. However, no local recurrence or metastasis has been
detected 2 months post-surgery. The main anatomic sites of liposarcomas are the
retroperitoneum and lower extremities; only 19 liposarcoma cases of the anterior
chest wall have been reported in Japan.
PMID- 25132043
TI - Reversal of Type 2 diabetes after bariatric surgery is determined by the degree
of achieved weight loss in both short- and long-duration diabetes.
AB - AIM: To define the impact of duration of diabetes and extent of weight loss on
the reversibility of Type 2 diabetes after bariatric surgery. METHODS: Complete
data were collated from 89 individuals with Type 2 diabetes mellitus undergoing
any bariatric surgical procedure in a specialist bariatric centre. People with a
preoperative HbA1c < 43 mmol/mol (6.1%) were excluded. Diabetes duration was
defined as: short, < 4 years; medium, 4-8 years; and long, > 8 years. RESULTS: An
HbA1c of <43 mmol/mol (6.1%) was achieved by 62% of patients in the short
duration group and 26% of patients in the long-duration group. Normoglycaemia was
rarely achieved in the long-duration group if weight loss was < 25 kg. In the
whole cohort there was a clear relationship of greater weight loss with lower
HbA1c levels (Rs = -0.53; P < 0.0001). CONCLUSIONS: The study shows that the
degree of achieved weight loss is the major determinant of return to normal blood
glucose levels after bariatric surgery. Normoglycaemia can be achieved in long
duration Type 2 diabetes, but a greater degree of weight loss is required than
for short-duration diabetes.
PMID- 25132042
TI - [Effective treatment of metastatic rhabdomyosarcoma with pazopanib].
AB - Pazopanib, an oral tyrosine kinase inhibitor, is the first molecular-targeted
agent approved for the treatment of advanced soft tissue sarcoma(STS).
Rhabdomyosarcoma in adults is rare, accounting for less than 3%of all adult STS
cases. A 57-year old woman presented with cervical lymphadenopathy. Computed
tomography revealed a heterogeneous mass in the retroperitoneum, replacing the
entire right kidney. On the basis of the above findings, the patient was
diagnosed with alveolar rhabdomyosarcoma. She was first treated with 4 courses of
vincristine, actinomycin D, and cyclophosphamide(VAC), which resulted in a
partial response. Dose reduction and delay occurred owing to hematological
toxicity and febrile neutropenia. As second-line chemotherapy, the patient was
administered a single daily dose of 800 mg of pazopanib. Because of an episode of
hand-foot syndrome and hepatic impairment, the 800-mg daily dose of pazopanib was
reduced to a daily dose of 600 mg, which had to be further reduced to a daily
dose of 400 mg owing to fatigue and anorexia. The patient maintained a partial
response for a total of 4.3 months when treated with pazopanib. Therefore, this
drug may be a new treatment option for patients showing metastatic STS after
previous chemotherapy.
PMID- 25132044
TI - Echocardiographic and clinical response to cardiac resynchronization therapy in
heart failure patients with and without previous right ventricular pacing.
AB - AIMS: Right ventricular pacing (RVp) results in an electrocardiographic left
bundle branch block pattern and can lead to heart failure. This study aimed to
evaluate echocardiographic and clinical outcomes of heart failure patients with
RVp upgraded to cardiac resynchronization therapy (CRT), as they are frequently
excluded from multicentre studies. METHODS AND RESULTS: This observational study
assessed 655 consecutive patients with QRS >=120 ms and left ventricular ejection
fraction <=35%. There were 465 patients without significant previous RVp and 190
with RVp >40%. Echocardiograms were analysed pre-CRT and ~ 1 year post-CRT. Death
and heart failure hospitalizations were analysed using Cox regression, adjusted
for baseline characteristics. The RVp patients had smaller end-systolic volume (P
= 0.002), were older (P < 0.001), and had more atrial fibrillation (P < 0.001)
pre-CRT. Ejection fraction and proportion of ischaemic aetiology were similar.
One year following CRT implantation the ejection fraction response was greater in
the RVp group (8.3 +/- 9 vs. 5.8 +/- 9 units, P = 0.005). The RVp patients had an
adjusted 33% lower risk of death or heart failure hospitalization [hazard ratio
(HR) 0.67 95% confidence interval (CI) 0.51-0.89, P = 0.005], while tending to
have an adjusted lower risk of death (HR 0.73 95% CI 0.53-1.01, P = 0.055).
CONCLUSION: Despite similar ejection fraction pre-CRT, patients upgraded to CRT
with previous RVp have smaller end-systolic volume and respond to CRT at least as
well as, if not better than, other wide QRS heart failure patients. A greater
improvement in ejection fraction and a lower risk of death or heart failure
hospitalization when adjusted for baseline characteristics were seen in those
with previous RVp.
PMID- 25132045
TI - Sublethal effects of the beta-blocker sotalol at environmentally relevant
concentrations on the New Zealand mudsnail Potamopyrgus antipodarum.
AB - Monitoring sublethal effects of pharmaceuticals on nontarget species in aquatic
environments has become an important topic in ecotoxicology, yet few studies have
been conducted concerning the effects of beta-blockers on aquatic organisms. The
present study investigated the effects of the beta-blocker sotalol (SOT) at 3
environmentally relevant concentrations on life-history traits of the New Zealand
mudsnail Potamopyrgus antipodarum. Based on the pharmacodynamic properties of
SOT, the authors hypothesized reduced numbers of embryos in the brood pouches,
decelerated growth of adult snails, and smaller size of neonates, but no effect
on mortality rates of adults. Contrary to the hypothesis, the total number of
embryos was significantly higher after 56 d of exposure at nominal concentrations
of 0.05 ug/L and 1.0 ug/L by 107% and 73%, respectively. No differences in embryo
numbers were observed at earlier time-points. Therefore, the mode of action seems
to be an extension of the reproductive period rather than an increase of the
embryo production. Furthermore, our results indicate a hormetic dose-response
relationship, because no effects were observed at the highest test-concentration
(6.5 ug/L). Mortality, growth of adult snails, and neonate sizes were not
affected by the beta-blocker. Given the strong influence on reproduction, the
effects of sublethal concentrations of SOT and other beta-blockers deserve better
consideration in ecotoxicological risk assessment.
PMID- 25132047
TI - Salt-stress induced modulation of chlorophyll biosynthesis during de-etiolation
of rice seedlings.
AB - Chlorophyll biosynthesis in plants is subjected to modulation by various
environmental factors. To understand the modulation of the chlorophyll (Chl)
biosynthesis during greening process by salt, 100-200 mM NaCl was applied to the
roots of etiolated rice seedlings 12 h prior to the transfer to light.
Application of 200 mM NaCl to rice seedlings that were grown in light for further
72 h resulted in reduced dry matter production (-58%) and Chl accumulation (
66%). Ionic imbalance due to salinity stress resulted in additional
downregulation (41-45%) of seedling dry weight, Chl and carotenoid contents over
and above that of similar osmotic stress induced by polyethylene glycol.
Downregulation of Chl biosynthesis may be attributed to decreased activities of
Chl biosynthetic pathway enzymes, i.e. 5-aminolevulinic acid (ALA) dehydratase
(EC-2.4.1.24), porphobilinogen deaminase (EC-4.3.1.8), coproporphyrinogen III
oxidase (EC-1.3.3.3), protoporphyrinogen IX oxidase (EC-1.3.3.4), Mg
protoporphyrin IX chelatase (EC-6.6.1.1) and protochlorophyllide oxidoreductase
(EC-1.3.33.1). Reduced enzymatic activities were due to downregulation of their
protein abundance and/or gene expression in salt-stressed seedlings. The extent
of downregulation of ALA biosynthesis nearly matched with that of
protochlorophyllide and Chl to prevent the accumulation of highly photosensitive
photodynamic tetrapyrroles that generates singlet oxygen under stress conditions.
Although, ALA synthesis decreased, the gene/protein expression of glutamyl-tRNA
reductase (EC-1.2.1.70) increased suggesting it may play a role in acclimation to
salt stress. The similar downregulation of both early and late Chl biosynthesis
intermediates in salt-stressed seedlings suggests a regulatory network of genes
involved in tetrapyrrole biosynthesis.
PMID- 25132046
TI - Analysis of genetic mutations in Chinese patients with systemic primary carnitine
deficiency.
AB - Systemic primary carnitine deficiency (CDSP) is caused by mutations in SLC22A5
gene, which encodes organic cation transporter 2(OCTN2). CDSP leads to skeletal
or cardiac myopathy and hepatic encephalopathy. The present study aimed to
identify SLC22A5 gene mutations and analyze the potential relationship between
genotype and clinical symptoms in 20 Chinese patients with CDSP. The complete
coding region of the SLC22A5 gene including intron-exon boundaries were amplified
and sequenced in all patients. Eighteen different mutations were found; of which,
nine were novel. The mutations clustering in exons 1 and 4 accounted for 66.7% of
all mutant alleles (26/39). The c.760C>T (p. R254X) was the most frequent
mutation (25.6%, 10/39), suggesting it as an ethnic founder mutation. The
relationship between genotype and phenotype was investigated in patients carrying
the R254X mutation. Homozygous patients with R254X were late-onset cases who
presented with dilated cardiomyopathy and muscle weakness after 1 year of age.
Compound heterozygous patients carrying R254X, combined with other missense
mutations occurred in very specific positions, dramatically altered OCTN2 protein
function. Based on the analysis of case studies, a clear relationship between
free carnitine (C0) level in plasma and OCTN2 genotype was not found in the
present work, however, the low plasma C0 level could not indicate disease
severity or genotype. Further functional studies with a large sample size are
required to understand the relationship between R254X mutation and CDSP.
PMID- 25132048
TI - Effects of developmental methylphenidate (MPH) treatment on monoamine
neurochemistry of male and female rats.
AB - Attention Deficit Hyperactivity Disorder (ADHD) is estimated to affect 4-5% of
the adult human population (Kessler et al., 2006; Willcutt, 2012). Often
prescribed to attenuate ADHD symptoms (Nair and Moss, 2009), methylphenidate
hydrochloride (MPH) can have substantial positive effects. However, there is a
paucity of literature regarding its use during pregnancy. Thus, adult women with
ADHD face a difficult decision when contemplating pregnancy. In this study,
pregnant Sprague-Dawley rats were orally treated a total of 0 (water), 6 (low),
18 (medium), or 42 (high) mg MPH/kg body weight/day (divided into three doses) on
gestational days 6-21 (i.e., the low dose received 2 mg MPH/kg body weight
3*/day). Offspring were orally treated with the same daily dose as their dam
(divided into two doses) on postnatal days (PNDs) 1-21. One offspring/sex/litter
was sacrificed at PND 22 or PND 104 (n=6-7/age/sex/treatment group) and the
striatum was quickly dissected and frozen. High Performance Liquid Chromatography
(HPLC) coupled to a Photo Diode Array detector (PDA) was used to analyze
monoamine content in the striatum of one side while a sandwich ELISA was used to
analyze tyrosine hydroxylase (TH) from the other side. Age significantly affected
monoamine and metabolite content as well as turnover ratios (i.e., DA, DOPAC,
HVA, DOPAC/DA, HVA/DA, 5-HT and 5-HIAA); however, there were no significant
effects of sex. Adult rats of the low MPH group had higher DA levels than control
adults (p<0.05). At both ages, subjects of the low MPH group had higher TH levels
than controls (p<0.05), although neither effect (i.e., higher DA or TH levels)
exhibited an apparent dose-response. PND 22 subjects of the high MPH treatment
group had higher ratios of HVA/DA and DOPAC/DA than same-age control subjects
(p<0.05). The increased TH levels of the low MPH group may be related to the
increased DA levels of adult rats. While developmental MPH treatment appears to
have some effects on monoamine system development, further studies are required
to determine if these alterations manifest as functional changes in behavior.
PMID- 25132050
TI - The development of a classification schema for arts-based approaches to knowledge
translation.
AB - BACKGROUND: Arts-based approaches to knowledge translation are emerging as
powerful interprofessional strategies with potential to facilitate evidence
uptake, communication, knowledge, attitude, and behavior change across healthcare
provider and consumer groups. These strategies are in the early stages of
development. To date, no classification system for arts-based knowledge
translation exists, which limits development and understandings of effectiveness
in evidence syntheses. PURPOSE: We developed a classification schema of arts
based knowledge translation strategies based on two mechanisms by which these
approaches function: (a) the degree of precision in key message delivery, and (b)
the degree of end-user participation. We demonstrate how this classification is
necessary to explore how context, time, and location shape arts-based knowledge
translation strategies. DISCUSSION: Classifying arts-based knowledge translation
strategies according to their core attributes extends understandings of the
appropriateness of these approaches for various healthcare settings and provider
groups. The classification schema developed may enhance understanding of how,
where, and for whom arts-based knowledge translation approaches are effective,
and enable theorizing of essential knowledge translation constructs, such as the
influence of context, time, and location on utilization strategies. LINKING
EVIDENCE TO ACTION: The classification schema developed may encourage systematic
inquiry into the effectiveness of these approaches in diverse interprofessional
contexts.
PMID- 25132051
TI - Neonicotinoids and bumblebees (Bombus terrestris): effects on nectar consumption
in individual workers.
AB - BACKGROUND: The objective of this study was to quantify whether the presence of
three different neonicotinoid insecticides (imidacloprid, thiamethoxam or
clothianidin) in sucrose solution results in antifeedant effects in individual
worker bumblebees (Bombus terrestris), and, if so, whether this effect is
reversible if bees are subsequently offered untreated feed. RESULTS: Bees exposed
to imidacloprid displayed a significant dose-dependent reduction in consumption
at 10 and 100 ug L(-1), which was reversed when untreated feed was offered. No
consistent avoidance/antifeedant response to nectar substitute with thiamethoxam
was detected at the more field-realistic dose rates of 1 and 10 ug L(-1), and
exposure to the very high 100 ug L(-1) dose rate was followed by 100% mortality
of experimental insects. No reduction in food intake was recorded at 1 ug
clothianidin L(-1), reduced consumption was noted at 10 ug clothianidin L(-1) and
100% mortality occurred when bees were exposed to rates of 100 ug clothianidin L(
1). CONCLUSION: This study provides evidence of a direct antifeedant effect of
imidacloprid and clothianidin in individual bumblebees but highlights that this
may be a compound-specific effect.
PMID- 25132052
TI - A photoswitchable bis-azo derivative with a high temporal resolution.
AB - The novel photoswitchable bis-azo derivative reported herein shows a high
temporal resolution of 2 * 10(8) times between the thermal relaxation rates of
its two constituting photochromes. Moreover, the slow and fast azo building
blocks of this molecular construct can be triggered by using UV and visible
light, respectively.
PMID- 25132053
TI - Butterfly-shape scalp excision: a single stage surgical technique for cutis
verticis gyrata.
PMID- 25132054
TI - Response to 'Uterine fundal pressure: is it really a culprit of poor maternal and
neonatal outcome?' by Shigeki Matsubara.
PMID- 25132056
TI - Part one: for the motion. Venous perforator surgery is proven and does reduce
recurrences.
PMID- 25132049
TI - A-kinase anchoring proteins: cAMP compartmentalization in neurodegenerative and
obstructive pulmonary diseases.
AB - The universal second messenger cAMP is generated upon stimulation of Gs protein
coupled receptors, such as the beta2 -adreneoceptor, and leads to the activation
of PKA, the major cAMP effector protein. PKA oscillates between an on and off
state and thereby regulates a plethora of distinct biological responses. The
broad activation pattern of PKA and its contribution to several distinct cellular
functions lead to the introduction of the concept of compartmentalization of
cAMP. A-kinase anchoring proteins (AKAPs) are of central importance due to their
unique ability to directly and/or indirectly interact with proteins that either
determine the cellular content of cAMP, such as beta2 -adrenoceptors, ACs and
PDEs, or are regulated by cAMP such as the exchange protein directly activated by
cAMP. We report on lessons learned from neurons indicating that maintenance of
cAMP compartmentalization by AKAP5 is linked to neurotransmission, learning and
memory. Disturbance of cAMP compartments seem to be linked to neurodegenerative
disease including Alzheimer's disease. We translate this knowledge to
compartmentalized cAMP signalling in the lung. Next to AKAP5, we focus here on
AKAP12 and Ezrin (AKAP78). These topics will be highlighted in the context of the
development of novel pharmacological interventions to tackle AKAP-dependent
compartmentalization.
PMID- 25132057
TI - Part two: against the motion. Venous perforator surgery is unproven and does not
reduce recurrences.
PMID- 25132055
TI - An historical perspective on health-risk awareness and unhealthy behaviour:
cigarette smoking in the United States 1949-1981.
AB - OBJECTIVE: This paper investigates the change through time in the perception of
smoking-related health harm and smoking behaviour from 1949 to 1981. BACKGROUND
AND CONTEXT: A variety of common behaviours can be linked to chronic disease risk
smoking, over-eating, and excessive sitting, to name a few. Changing behaviours
to reduce exposure to such risks can be an effort that spans generations and
decades. SETTING AND PARTICIPANTS: Respondents to Gallup Poll surveys in the
United States from 1949, 1954, 1957, 1971, 1972, 1977 and 1981. METHODS:
Graphical analysis and probit regression are used to investigate trends through
time and statistical associations of smoking with the perception of smoking
related health risks and other socio-demographic variables. INTERVENTION AND MAIN
VARIABLE STUDIED: Perceived smoking health risk. MAIN OUTCOME MEASURE: Smoking
participation. RESULTS AND CONCLUSION: Our findings include the proportions of
individuals who were self-reported smokers fell between 1949 and 1981, from 0.48
to 0.34. Among smokers, the proportion who believed smoking was harmful increased
from 0.52 in 1949 to 0.81 in 1981. By 1981, the proportion of non-smokers who
believed smoking was harmful was 0.98. A negative association between belief in
smoking harm and the decision to smoke was shown in regression analysis. This
association became more pronounced over the three decades under study.
PMID- 25132058
TI - Electrophoretic karyotyping of Hypsizygus marmoreus and evaluation of variation
among its basidiospores.
AB - The molecular karyotype of Hypsizygus marmoreus was explored by contour-clamped
homogeneous electric field gel electrophoresis. Eleven chromosomal bands were
separated from the dikaryotic mycelia of H. marmoreus (strain Hm 3-10), and the
chromosomes ranged in size from 1.9 to 5.8 Mb. The total genome size of the
strain was estimated to be 36.3 Mb. The chromosome numbers were also confirmed by
telomere fingerprinting, and 22 telomeric bands were identified. This result
suggests that 11 chromosomes exist in Hm 3-10. The marker sequences for each
chromosome were determined and were applied to identify each chromosome.
Karyotyping and Southern blot analysis revealed that the size of chromosomes in
the basidiospores were greatly different from those of parental dikaryon Hm 3-10
cells.
PMID- 25132059
TI - Retinoid metabolism in invertebrates: when evolution meets endocrine disruption.
AB - Recent genomic and biochemical evidence in invertebrate species pushes back the
origin of the retinoid metabolic and signaling modules to the last common
ancestor of all bilaterians. However, the evolution of retinoid pathways are far
from fully understood. In the majority of non-chordate invertebrate lineages, the
ongoing functional characterization of retinoid-related genes (metabolism and
signaling pathways), as well as the characterization of the endogenous retinoid
content (precursors and active retinoids), is still incomplete. Despite limited,
the available data supports the presence of biologically active retinoid pathways
in invertebrates. Yet, the mechanisms controlling the spatial and temporal
distribution of retinoids as well as their physiological significance share
similarities and differences with vertebrates. For instance, retinol storage in
the form of retinyl esters, a key feature for the maintenance of retinoid
homeostatic balance in vertebrates, was only recently demonstrated in some
mollusk species, suggesting that such ability is older than previously
anticipated. In contrast, the enzymatic repertoire involved in this process is
probably unlike that of vertebrates. The suggested ancestry of active retinoid
pathways implies that many more metazoan species might be potential targets for
endocrine disrupting chemicals. Here, we review the current knowledge about the
occurrence and functionality of retinoid metabolic and signaling pathways in
invertebrate lineages, paying special attention to the evolutionary origin of
retinoid storage mechanisms. Additionally, we summarize existing information on
the endocrine disruption of invertebrate retinoid modules by environmental
chemicals. Research priorities in the field are highlighted.
PMID- 25132060
TI - A survey of gastro-intestinal parasitic infection in domestic and wild birds in
Chittagong and Greater Sylhet, Bangladesh.
AB - A survey of gastrointestinal parasitic infection as determined by faecal
examination was conducted among domestic and wild birds in Bangladesh. Birds were
sampled from households, wet markets and wetlands in Chittagong and Greater
Sylhet districts during April 2012 to February 2013. Mist nets were used to catch
resident wild and migratory birds. The overall prevalence of parasitic infection
ranged among locations from 25 to 55% in indigenous domestic ducks (live bird
samples=304), 20% in resident wild birds (environmental faecal samples=40) and
40% in migratory birds (live bird samples=35). The prevalence of parasitic
infection was significantly higher in indigenous domestic ducks collected during
summer (39%) than winter (22%) (p=0.04). In domestic indigenous ducks and Muscovy
ducks, both single and multiple types of parasitic infections were found.
However, other domestic birds and wild birds often had a single type of parasitic
infection. Ascaridia spp. with an average egg load of 50-900, was commonly
detected in faecal samples of domestic and wild birds in this study. Other
identified parasites were Capillaria spp. and Heterakis spp. both in domestic and
wild birds. Improvement of biosecurity measures for household duck farms through
educating and motivating household farmers could help mitigate the effects of
parasitic infection on production.
PMID- 25132061
TI - Risk factors for occupational brucellosis among veterinary personnel in Turkey.
AB - Veterinarians and veterinary technicians are at risk for occupational
brucellosis. We described the risk factors of occupational brucellosis among
veterinary personnel in Turkey. A multicenter retrospective survey was performed
among veterinary personnel who were actively working in the field. Of 712
veterinary personnel, 84 (11.8%) had occupational brucellosis. The median number
of years since graduation was 7 (interquartile ranges [IQR], 4-11) years in the
occupational brucellosis group, whereas this number was 9 (IQR, 4-16) years in
the non-brucellosis group (p<0.001). In multivariable analysis, working in the
private sector (odds ratio [OR], 2.8; 95% confidence interval [95% CI], 1.55
5.28, p=0.001), being male (OR, 4.5; 95% CI, 1.05-18.84, p=0.041), number of
performed deliveries (OR, 1.01; 95% CI, 1.002-1.02, p=0.014), and injury during
Brucella vaccine administration (OR, 5.4; 95% CI, 3.16-9.3, p<0.001) were found
to be risk factors for occupational brucellosis. We suggest that all veterinary
personnel should be trained on brucellosis and the importance of using personal
protective equipment in order to avoid this infection.
PMID- 25132063
TI - Similarity between generic and brand-name antihypertensive drugs for primary
prevention of cardiovascular disease: evidence from a large population-based
study.
AB - BACKGROUND: Although generic and earlier brand-name counterparts are
bioequivalent, their equivalence in preventing relevant clinical outcomes is of
concern. OBJECTIVE: To compare effectiveness of generic and brand-name
antihypertensive drugs for preventing the onset of cardiovascular (CV) outcomes.
DESIGN AND SUBJECTS: A population-based, nested case-control study was carried
out by including the cohort of 78 520 patients from Lombardy (Italy) aged 18
years or older who were newly treated with antihypertensive drugs during 2005.
Cases were the 2206 patients who experienced a hospitalization for CV disease
from initial prescription until 2011. One control for each case was randomly
selected from the same cohort that generated cases. Logistic regression was used
to model the CV risk associated with starting on and/or continuing with generic
or brand-name agents. RESULTS: There was no evidence that patients who started on
generics experienced different CV risk than those on brand-name product (OR 0.86;
95% CI 0.63-1.17). Patients at whom generics were main dispensed had not
significantly difference in CV outcomes than those mainly on brand-name agents
(OR 1.19; 95% CI 0.86-1.63). Compared with patients who kept initial brand-name
therapy, those who experienced brand-to-generic or generic-to-brand switches, and
those always on generics, did not show differential CV risks, being the
corresponding ORs (and 95% CIs), 1.18 (0.96-1.47), 0.87 (0.63-1.21) and 1.08
(0.80-1.46). CONCLUSIONS: Our findings do not support the notion that brand-name
antihypertensive agents are superior to generics for preventing CV outcomes in
the real-world clinical practice.
PMID- 25132062
TI - Deletion of serine/arginine-rich splicing factor 3 in hepatocytes predisposes to
hepatocellular carcinoma in mice.
AB - Alterations in RNA splicing are associated with cancer, but it is not clear
whether they result from malignant transformation or have a causative role. We
show here that hepatocyte-specific deletion of serine/arginine-rich splicing
factor 3 (SRSF3) impairs hepatocyte maturation and metabolism in early adult
life, and mice develop spontaneous hepatocellular carcinoma (HCC) with aging.
Tumor development is preceded by chronic liver disease with progressive steatosis
and fibrosis. SRSF3 protects mice against CCl4 -induced fibrosis and
carcinogenesis and suppresses inclusion of the profibrogenic EDA exon in
fibronectin 1. Loss of SRSF3 increases expression of insulin-like growth factor 2
and the A-isoform of the insulin receptor, allowing aberrant activation of
mitogenic signaling, promotes aberrant splicing and expression of epithelial to
mesenchymal transition (EMT) genes, and activates Wnt/beta-catenin signaling
leading to c-Myc induction. Finally, SRSF3 expression is either decreased or the
protein mislocalized in human HCC. CONCLUSION: Our data suggest a potential role
for SRSF3 in preventing hepatic carcinogenesis by regulating splicing to suppress
fibrosis, mitogenic splicing, and EMT. Thus, these mice may provide an attractive
model to discover the pathogenic mechanisms linking aberrant pre-messenger RNA
splicing with liver damage, fibrosis, and HCC.
PMID- 25132064
TI - Impact of defective interfering particles on virus replication and antiviral host
response in cell culture-based influenza vaccine production.
AB - During the replication of influenza viruses, defective interfering particles
(DIPs) can be generated. These are noninfectious deletion mutants that require
coinfection with a wild-type virus but interfere with its helper virus
replication. Consequently, coinfected cells mainly produce DIPs. Little is known
about how such noninfectious virus particles affect the virus yield of cell
culture-based influenza vaccine production. We compared infections of Madin-Darby
canine kidney cells with two seed virus preparations of the influenza virus
strain A/Puerto Rico/8/34 that contain different amounts of DIPs. A combination
of conventional RT-PCR, RT-qPCR, and flow cytometry revealed that DI genomes
indeed strongly accumulate in coinfected cells and impede the viral RNA
synthesis. Additionally, cells infected at the higher DIP concentration showed a
stronger antiviral response characterized by increased interferon-beta expression
and apoptosis induction. Furthermore, in the presence of DIPs, a significant
fraction of cells did not show any productive accumulation of viral proteins at
all. Together, these effects of DIPs significantly reduce the virus yield.
Therefore, the accumulation of DIPs should be avoided during influenza vaccine
production which can be achieved by quality controls of working seed viruses
based on conventional RT-PCR. The strategy for the depletion of DIPs presented
here can help to make cell culture-based vaccine production more reliable and
robust.
PMID- 25132065
TI - Effect of lithium chloride on the production and sialylation of Fc-fusion protein
in Chinese hamster ovary cell culture.
AB - Lithium chloride (LiCl), which is a specific inhibitor of glycogen synthase
kinase-3beta, is known to induce cell cycle arrest at the G2/M phase and to
regulate apoptosis. To determine the potential of LiCl as a chemical additive to
enhance specific productivity (q p) of recombinant Chinese hamster ovary (rCHO)
cells through cell cycle arrest at G2/M phase, rCHO cells producing Fc-fusion
protein were cultivated in serum-free media with LiCl concentrations ranging from
0 to 20 mM. The addition of LiCl induced cell cycle arrest at G2/M phase and
thereby decreased the specific cell growth rate. However, LiCl increased q p in a
dose-dependent manner. The beneficial effect of LiCl on q p outweighed its
detrimental effect on MU, resulting in improved maximum Fc-fusion protein
concentration (MFPC) at 10 mM LiCl. The q p and MFPC in the bioreactor culture
with 10 mM LiCl were 5.0 and 2.1 times higher than those without LiCl,
respectively. In addition, the presence of LiCl at 10 mM did not significantly
affect either intracellular alpha2,3-ST or extracellular sialidase activity. LiCl
also inhibited apoptosis of cells in the decline phase of growth by increasing
Bcl-2 expression. Taken together, the results obtained in this study demonstrate
the potential of LiCl as a q p-enhancing additive in CHO cell culture for
improved recombinant protein production.
PMID- 25132066
TI - Patients' perspectives on the role of their general practitioner after receiving
an advanced cancer diagnosis.
AB - The aim of this study was to explore patients' perspectives on the role of their
general practitioner (GP) after an advanced cancer diagnosis. A qualitative
research approach was used. Semi-structured interviews were conducted and data
were analysed using a constant comparative methodology. Participants were
eligible if they were diagnosed with advanced cancer and referred for palliative
radiotherapy. Data saturation was achieved after 21 interviews. Key themes
included (1) obtaining diagnosis and referral for advanced cancer treatment; (2)
preference for specialist oncology care; (3) a preference for GP to act as an
advocate; and (4) obtaining ongoing routine care from their GP. GP involvement in
the patients' management was dependent on: time since diagnosis, GP's involvement
in diagnosis and referral, doctor/patient relationship, additional chronic
conditions requiring management, frequency of seeing oncologist and specialist
recommendation to involve GP. Patients want GPs to have varying levels of
involvement following an advanced cancer diagnosis. Not all communication between
GPs and patients was positive suggesting communication skills training may be a
priority. Patients wished to maintain continunity of care for their non-cancer
related issues and healthcare of their family members. Future research needs to
focus on working with GPs to increase their role in the management of advanced
cancer.
PMID- 25132067
TI - RNA structural analysis by evolving SHAPE chemistry.
AB - RNA is central to the flow of biological information. From transcription to
splicing, RNA localization, translation, and decay, RNA is intimately involved in
regulating every step of the gene expression program, and is thus essential for
health and understanding disease. RNA has the unique ability to base-pair with
itself and other nucleic acids to form complex structures. Hence the information
content in RNA is not simply its linear sequence of bases, but is also encoded in
complex folding of RNA molecules. A general chemical functionality that all RNAs
have is a 2'-hydroxyl group in the ribose ring, and the reactivity of the 2'
hydroxyl in RNA is gated by local nucleotide flexibility. In other words, the 2'
hydroxyl is reactive at single-stranded and conformationally flexible positions
but is unreactive at nucleotides constrained by base-pairing. Recent efforts have
been focused on developing reagents that modify RNA as a function of RNA 2'
hydroxyl group reactivity. Such RNA structure probing techniques can be read out
by primer extension in experiments termed RNA SHAPE (selective 2'- hydroxyl
acylation and primer extension). Herein, we describe the efforts devoted to the
design and utilization of SHAPE probes for characterizing RNA structure. We also
describe current technological advances that are being applied to utilize SHAPE
chemistry with deep sequencing to probe many RNAs in parallel. The merging of
chemistry with genomics is sure to open the door to genome-wide exploration of
RNA structure and function.
PMID- 25132069
TI - Decreased lipases and fatty acid and glycerol transporter could explain reduced
fat in diabetic morbidly obese.
AB - OBJECTIVE: The possible differences were investigated in 32 morbidly obese
patients depending on whether they were "healthy" or had dyslipidemia and/or type
2 diabetes. METHODS: Lipid metabolism and insulin resistance were analyzed in
subcutaneous (SAT) and visceral adipose tissue (VAT) before and during 6 and 12
months after Roux-en-Y gastric bypass. RESULTS: Significant differences have been
found in lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activities
in SAT from the different obese group versus normal weight (control) but not
between them. The reduced lipase activities in VAT were 43 and 19% smaller (22
and 4% smaller, respectively, vs. control) than the "healthy" obese group for LPL
and HSL, respectively, and were accompanied with a reduced expression of these
lipases, as well as decreased expression of FAT/CD36, FABP4, and AQ7 in that
tissue. In addition, the expression of the other genes measured showed a
downregulation not only versus the "healthy" obese but also versus the normal
weight group. CONCLUSIONS: Being obese is not "healthy," but it is even less so
if morbidly obese patients with diabetes and dyslipidemia were considered. The
reduced fat accumulation in these patients may be attributed to the decrease of
the expression and activity of the lipases of their adipose tissue.
PMID- 25132068
TI - The scientific quest for lasting youth: prospects for curing aging.
AB - People have always sought eternal life and everlasting youth. Recent
technological breakthroughs and our growing understanding of aging have given
strength to the idea that a cure for human aging can eventually be developed. As
such, it is crucial to debate the long-term goals and potential impact of the
field. Here, I discuss the scientific prospect of eradicating human aging. I
argue that curing aging is scientifically possible and not even the most
challenging enterprise in the biosciences. Developing the means to abolish aging
is also an ethical endeavor because the goal of biomedical research is to allow
people to be as healthy as possible for as long as possible. There is no
evidence, however, that we are near to developing the technologies permitting
radical life extension. One major difficulty in aging research is the time and
costs it takes to do experiments and test interventions. I argue that unraveling
the functioning of the genome and developing predictive computer models of human
biology and disease are essential to increase the accuracy of medical
interventions, including in the context of life extension, and exponential growth
in informatics and genomics capacity might lead to rapid progress. Nonetheless,
developing the tools for significantly modifying human biology is crucial to
intervening in a complex process like aging. Yet in spite of advances in areas
like regenerative medicine and gene therapy, the development of clinical
applications has been slow and this remains a key hurdle for achieving radical
life extension in the foreseeable future.
PMID- 25132071
TI - Catalytic activity of an encaged Verkade's superbase in a base-catalyzed Diels
Alder reaction.
AB - Organocatalysis in a confined space has been performed through encapsulation of a
proazaphosphatrane superbase in a hemicryptophane host. The resulting catalyst
displays good to high catalytic activity in the base-catalyzed Diels-Alder
reactions investigated. A comparison with the model superbase, which lacks a
cavity, shows much higher diastereomeric excess with the encaged
proazaphosphatrane for the reaction of 3-hydroxy-2-pyrone with N-methylmaleimide.
The use of an encaged superbase as organocatalyst is unprecedented and highlights
how the confinement may impact the stereoselectivity.
PMID- 25132070
TI - Combining family- and population-based imputation data for association analysis
of rare and common variants in large pedigrees.
AB - In the last two decades, complex traits have become the main focus of genetic
studies. The hypothesis that both rare and common variants are associated with
complex traits is increasingly being discussed. Family-based association studies
using relatively large pedigrees are suitable for both rare and common variant
identification. Because of the high cost of sequencing technologies, imputation
methods are important for increasing the amount of information at low cost. A
recent family-based imputation method, Genotype Imputation Given Inheritance
(GIGI), is able to handle large pedigrees and accurately impute rare variants,
but does less well for common variants where population-based methods perform
better. Here, we propose a flexible approach to combine imputation data from both
family- and population-based methods. We also extend the Sequence Kernel
Association Test for Rare and Common variants (SKAT-RC), originally proposed for
data from unrelated subjects, to family data in order to make use of such imputed
data. We call this extension "famSKAT-RC." We compare the performance of famSKAT
RC and several other existing burden and kernel association tests. In simulated
pedigree sequence data, our results show an increase of imputation accuracy from
use of our combining approach. Also, they show an increase of power of the
association tests with this approach over the use of either family- or population
based imputation methods alone, in the context of rare and common variants.
Moreover, our results show better performance of famSKAT-RC compared to the other
considered tests, in most scenarios investigated here.
PMID- 25132074
TI - Improved hydroxyurea effect with the use of text messaging in children with
sickle cell anemia.
AB - BACKGROUND: In children with sickle cell anemia (SCA), hydroxyurea reduces
morbidity, but adherence is frequently suboptimal. Because most families of
children with SCA have access to cellular telephone services, we assessed the
impact of text messaged reminders as a tool to improve adherence to hydroxyurea.
PROCEDURE: All patients <19 years of age with HbSS or HbSbeta(0) thalassemia who
were treated with hydroxyurea at a maximal tolerated dosage (MTD) at St. Jude
Children's Research Hospital Comprehensive Pediatric Sickle Cell Program and who
received automated text message reminders (SIMON(r)) were retrospectively
identified. Laboratory parameters, hospitalizations, and medication possession
ratios (MPR) prior to and after initiation of SIMON(r) were compared to assess
the impact of SIMON(r). RESULTS: Of the 97.3% of families with access to a cell
phone, 91% elected to receive text message reminders. Among 55 children receiving
hydroxyurea at MTD, laboratory parameters reflected waning medication compliance
during the 12 months prior to SIMON(r). Following initiation of SIMON(r),
children had higher mean corpuscular volumes, hemoglobin levels and fetal
hemoglobin percentages and lower absolute reticulocyte counts and bilirubin
levels, suggesting improved medication adherence. Hospitalizations were uncommon
before and after SIMON(r), and medication possession ratios (MPRs) were high
before and after SIMON(r), neither was significantly changed. CONCLUSIONS:
SIMON(r) was feasible and improved hematologic parameters in children with SCA
receiving hydroxyurea at a MTD. Future work will include extension of this
technology to children with other chronic medical conditions who require daily
use of medication.
PMID- 25132073
TI - Transforming growth factor-beta1 mediates psoriasis-like lesions via a Smad3
dependent mechanism in mice.
AB - Transforming growth factor (TGF)-beta1 signals through downstream Smad-dependent
and -independent pathways to exert its biological actions. It has been reported
that overexpression of TGF-beta1 results in the development of psoriasis-like
lesions in a mouse model of K5.TGF-beta(WT) transgenic mice. However, the
signalling mechanisms by which TGF-beta1 mediates the development of psoriasis
like lesions remain unknown. The aim of the present study was to investigate the
hypothesis that TGF-beta1 mediates the development of psoriasis-like lesions via
a Smad3-dependent mechanism. This was tested in a mouse model of K5.TGF-beta(WT)
transgenic mice by blocking TGF-beta signalling with a specific Smad3 inhibitor.
Topical treatment with a Smad3 inhibitor markedly blocked TGF-beta/Smad3
signalling and progressive psoriasis-like lesions in K5.TGF-beta(WT) transgenic
mice, as evidenced by decreased skin severity scores, double skin fold thickness
(DSFT) scores, infiltration of CD3(+) T cells and F4/80(+) macrophages and the
degree of fibrosis in the dermis. This was associated with a marked reduction in
TGF-beta1, interleukin (IL)-6, IL-23 and IL-17A both locally in skin plaque
lesions and systemically in the plasma, resulting in inhibition of both the T
helper (Th) 17 cell transcription factor RORgammat and accumulation of CD4(+) IL
17A(+) cells within the skin plaque lesions. In conclusion, TGF-beta1 mediates
the development of psoriasis-like lesions via a Smad3-dependent, Th17-mediated
mechanism. Targeting TGF-beta/Smad3 signalling with a Smad3 inhibitor may
represent a novel and effective therapy for psoriasis.
PMID- 25132072
TI - Maternal periconceptional alcohol consumption and congenital limb deficiencies.
AB - BACKGROUND: Women of childbearing age report high rates of alcohol consumption,
which may result in alcohol exposure during early pregnancy. Epidemiological
research on congenital limb deficiencies (LDs) and periconceptional exposure to
alcohol is inconclusive. METHODS: Data from the National Birth Defects Prevention
Study (NBDPS) were examined for associations between LDs and patterns of maternal
periconceptional (1 month before conception through the first trimester) alcohol
consumption among LD case (n = 906) and unaffected control (n = 8352) pregnancies
with expected delivery dates from 10/1997 through 12/2007. Adjusted odds ratios
(aORs) and 95% confidence intervals were estimated from unconditional logistic
regression analysis for all LDs combined, specific LD subtypes (preaxial/terminal
transverse), and LD anatomic groups (upper/lower limbs); interactions with folic
acid (FA) supplementation were tested. RESULTS: When compared with nondrinkers,
inverse associations were found between all LDs combined, preaxial, and upper LDs
and any reported periconceptional alcohol consumption (aORs ranged from 0.56
0.83), drinking without binging (aORs: 0.53-0.75), and binge drinking (>=4
drinks/occasion) (aORs: 0.64-0.94); however, none of the binge drinking aORs were
statistically significant. Stratification by alcohol type showed inverse
associations between all LDs combined, preaxial, transverse, and upper and lower
LDs for drinking without binging of wine only (aORs: 0.39-0.67) and between all
LDs combined and upper LDs for drinking without binging of combinations of
alcohol (aORs: 0.63-0.87). FA did not modify observed associations. CONCLUSION:
Maternal periconceptional alcohol consumption did not emerge as a teratogen for
selected LDs in the NBDPS. Future studies should evaluate additional rare LDs
among more highly exposed populations.
PMID- 25132075
TI - Molecular analysis of the interspousal transmission of hepatitis B virus in two
Japanese patients who acquired fulminant hepatitis B after 50 and 49 years of
marriage.
AB - A 71-year-old (C1I) and 69-year-old (C2I) Japanese female contracted fulminant
hepatitis B after 50 and 49 years of marriage, respectively. Both index cases
exhibited high levels of anti-HBc IgM antibodies (24.2 and 31.5 S/CO,
respectively), suggestive of acute hepatitis B virus (HBV) infection, although
they had no discernible risk factors for HBV infection, except for chronically
HBV-infected spouses with detectable HBV DNA (3.3 log copies/ml [C1S: 72-year
old] and 7.2 log copies/ml [C2S: 71-year-old]). The HBV genotype/subgenotype was
identical in each couple (B/B1 or C/C2). The HBV isolates from the index cases
and spouses shared a nucleotide sequence identity of 99.5% and 99.7%,
respectively, over the entire genome, and these four isolates had the highest
nucleotide sequence identity of only 97% to HBV isolates deposited in DNA
databases. Phylogenetic trees confirmed a close relationship of the HBV isolates
between C1I and C1S and between C2I and C2S, supported by a high bootstrap value
of 100% within each couple, indicating the transfer of HBV infection between
spouses. These four isolates shared a precore mutation of G1896A known to be
associated with fulminant hepatitis B. Although the history of sexual contact
within a reasonable incubation period was obscure for one stable, monogamous
couple (C1I and C1S), the other couple had a monogamous sexual relationship
within six months prior to disease onset. This study indicates that two elderly
Japanese patients with fulminant hepatitis B acquired HBV infection via
interspousal (most likely sexual) transmission during long-lasting marriages.
PMID- 25132076
TI - Retrospective analysis of treatment outcomes following reirradiation in
locoregionally recurrent head and neck cancer patients: A single institutional
study.
AB - AIM: To present a retrospective analysis of treatment outcomes following
reirradiation in locoregionally recurrent head and neck cancer patients at our
institute. METHODS: Thirty-one patients of head and neck cancer who presented
with a locoregional recurrence from April 2007 to April 2012 underwent salvage
reirradiation. Median dose of first-time radiation was 70 Gy. Median duration of
gap between the first and second course of radiation was 45.6 months. The median
dose of reirradiation was 60 Gy. Conformal radiotherapy technique in the form of
intensity modulated radiotherapy was used in 60% (17) of patients. Fourteen
patients received concurrent chemotherapy or immunotherapy. RESULTS: After a
median follow-up of 20.6 months, 12 patients were alive with no evidence of
disease. The 3-year disease-free survival and overall survival were 28.7 and
48.5%, respectively. Acute and late toxicities were reported in 29 and 61% of
patients, respectively. Severe grade 3 and 4 late complications were observed in
nine patients but none of them led to mortality. CONCLUSION: Reirradiation
appears to be both feasible and well tolerated in patients treated with previous
radiotherapy for recurrent and second primary head and neck cancer. Careful case
selection for reirradiation based on patient's performance status and tumor
characteristics is essential.
PMID- 25132077
TI - ARFI elastography as a complementary diagnostic method for mammary neoplasia in
female dogs - preliminary results.
AB - OBJECTIVES: To evaluate the applicability of acoustic radiation force impulse
elastography as a complementary method in diagnosing mammary neoplasia in dogs.
METHODS: Mammary tumours from 50 female dogs were evaluated and divided into two
groups: G1 (benign tissue) and G2 (malignant tumours). The nodules were assessed
by B-Mode ultrasonography, qualitative and quantitative acoustic radiation force
impulse elastography and histopathology. RESULTS: B-Mode ultrasound examination
was ineffective at separating the tumours into the two groups. Likewise, there
was no correlation between the grayscale images of the mammary tissue by
qualitative elastography. A difference was found in the deformity of the mammary
masses between the malignant and benign groups (P = 0 . 002). Using quantitative
elastography, the mean values of shear velocity were 3 . 33 m/s for malignant
tumours and 1 . 28 m/s for benign tissue (P < 0 . 0001). CLINICAL SIGNIFICANCE:
The use of acoustic radiation force impulse elastography may help to
differentiate between malignant and benign mammary neoplasms.
PMID- 25132079
TI - Regulation of mitochondrial apoptosis by Pin1 in cancer and neurodegeneration.
AB - Mitochondria are sensitive and efficient organelles that regulate essential
biological processes including: energy metabolism, decoding and transduction of
intracellular signals, and balance between cell death and survival. Of note,
dysfunctions in mitochondrial physiology are a general hallmark of cancer cells,
leading to transformation-related features such as altered cellular metabolism,
survival under stress conditions and reduced apoptotic response to chemotherapy.
Mitochondrial apoptosis is a finely regulated process that derives from
activation of multiple signaling networks. A crucial biochemical requirement for
transducing pro-apoptotic stimuli is represented by kinase-dependent
phosphorylation cascades. In this context a pivotal role is played by the prolyl
isomerase Pin1, which translates Ser/Thr-Pro phosphorylation into conformational
changes able to modify the activities of its substrates. In this review we will
discuss the impact of Pin1 in regulating various aspects of apoptosis in
different biological contexts with particular emphasis on cancer and
neurodegenerative diseases.
PMID- 25132078
TI - Efficacy of catheter ablation for persistent atrial fibrillation: a systematic
review and meta-analysis of evidence from randomized and nonrandomized controlled
trials.
AB - BACKGROUND: Catheter ablation (CA) is commonly performed for persistent atrial
fibrillation, but few high-quality randomized controlled trials (RCTs) exist,
leading to funding restrictions being proposed in several countries. We performed
a random-effects meta-analysis of RCTs and non-RCTs to assess the efficacy of CA
for persistent atrial fibrillation. METHODS AND RESULTS: We systematically
searched PubMed, EMBASE, CENTRAL, OpenGrey, and clinicaltrials.gov for RCTs and
non-RCTs reporting clinical outcomes after CA for persistent atrial fibrillation.
Forty-six eligible studies were identified containing 3819 patients. After a
single procedure, CA significantly reduced the risk of recurrent atrial
fibrillation compared with medical therapy (odds ratio [OR], 0.32; 95% confidence
interval [CI], 0.20-0.53; P<0.001). Outcomes were better if the pulmonary veins
were encircled (OR, 0.26; 95% CI, 0.09-0.74; P=0.01), and electrical isolation
reduced AF recurrence compared with purely anatomic encirclement (OR, 0.33; 95%
CI, 0.13-0.86; P=0.02). Linear ablation within the left atrium (OR, 0.22; 95% CI,
0.10-0.49; P<0.001), but not complex fractionated atrial electrogram ablation
(OR, 0.64; 95% CI, 0.35-1.18; P=0.15), significantly reduced AF recurrence.
Results were not improved by performing more extensive linear lesion sets (OR,
0.77; 95% CI, 0.41-1.43; P=0.40) or from biatrial ablation (OR, 0.62; 95% CI,
0.31-1.24; P=0.17). Where data were available, the relative benefits seen held
true both after a single or multiple procedure(s). Sensitivity analyses showed
that inclusion of non-RCTs increased statistical power without biasing the
calculated effect sizes. CONCLUSIONS: For patients with persistent atrial
fibrillation, CA achieves significantly greater freedom from recurrent atrial
fibrillation compared with medical therapy. The most efficacious strategy is
likely to combine isolation of the pulmonary veins with limited linear ablation
within the left atrium.
PMID- 25132080
TI - Mitochondrial macro-haplogroup JT may play a protective role in ovarian ageing.
AB - This study of 200 Caucasian women shows that the distribution of the mtDNA macro
haplogroups in patients with diminished ovarian reserve (DOR) differed
significantly from that of patients with normal ovarian reserve (NOR) (p=0.02).
The JT macro-haplogroup was significantly under-represented in DOR patients
compared with NOR patients (p=0.006) and compared with the estimated frequency of
18.8% in the general French population (p=0.0012). Our findings suggest that the
risk of a prematurely depleted ovarian reserve would be three times lower for
patients carrying the JT macro-haplogroup than for patients with any of the other
mtDNA haplogroups (odds ratio: 0.3; 95% CI: 0.13-0.74). If these preliminary
results are confirmed in larger independent studies, they should lead to the
better management of infertility.
PMID- 25132081
TI - Efficacy of liposome-encapsulated hemoglobin in a rat model of cerebral ischemia.
AB - Use of liposome-encapsulated hemoglobin (LEH) for oxygen delivery in the
treatment of cerebral ischemia has been studied previously and its expected
benefits confirmed. However, the relationship between the timing of
administration and the efficacy of LEH in cerebral ischemia has not been studied
in detail. We therefore investigated the therapeutic time window of LEH by using
a rat model of cerebral ischemia, as well as evaluating the contribution of
oxygen delivery to the efficacy of LEH. Dose-dependent effects and the
therapeutic time window of LEH were studied using models of transient and
permanent middle cerebral artery occlusion (MCAO), respectively, in SD rats. LEH
was intravenously administered at 0.5 h after the onset of ischemia in the
transient MCAO model and at 0.5, 2, 4, or 6 h in the permanent MCAO model.
Efficacy of LEH treatment was evaluated using the infarct volume, which was
examined with 2,3,5-triphenyltetrazolium chloride staining and estimated by
integrating the unstained areas in serial sections of cerebral tissue. Effects of
oxygen delivery by LEH were examined immunohistochemically with pimonidazole to
stain for areas of low oxygen tension in the tissue. LEH treatment dose
dependently reduced the cerebral infarct volume, which was especially significant
in the cortical region at doses of over 60 mg hemoglobin (Hb)/kg. In rats with
permanent MCAO, LEH administration at a dose of 300 mg Hb/kg at 0.5 h and 2 h
after the onset of cerebral ischemia significantly reduced cerebral infarct
volume. Furthermore, immunohistochemical staining with pimonidazole showed that
the areas of cerebral tissue that were hypoxic and had abnormal histological
structure were reduced after LEH treatment. These results indicated that LEH is
efficacious in the treatment of cerebral infarction secondary to MCAO and that
oxygen delivery to ischemic cerebral tissues by LEH administered early after the
onset of cerebral ischemia contributes to this effect.
PMID- 25132082
TI - L-Arabinose binding, isomerization, and epimerization by D-xylose isomerase: X
ray/neutron crystallographic and molecular simulation study.
AB - D-xylose isomerase (XI) is capable of sugar isomerization and slow conversion of
some monosaccharides into their C2-epimers. We present X-ray and neutron
crystallographic studies to locate H and D atoms during the respective
isomerization and epimerization of L-arabinose to L-ribulose and L-ribose,
respectively. Neutron structures in complex with cyclic and linear L-arabinose
have demonstrated that the mechanism of ring-opening is the same as for the
reaction with D-xylose. Structural evidence and QM/MM calculations show that in
the reactive Michaelis complex L-arabinose is distorted to the high-energy (5)S1
conformation; this may explain the apparent high KM for this sugar. MD-FEP
simulations indicate that amino acid substitutions in a hydrophobic pocket near
C5 of L-arabinose can enhance sugar binding. L-ribulose and L-ribose were found
in furanose forms when bound to XI. We propose that these complexes containing
Ni(2+) cofactors are Michaelis-like and the isomerization between these two
sugars proceeds via a cis-ene-diol mechanism.
PMID- 25132083
TI - HIV-1 envelope protein gp41: an NMR study of dodecyl phosphocholine embedded gp41
reveals a dynamic prefusion intermediate conformation.
AB - Human immunodeficiency viral (HIV-1) fusion is mediated by the viral envelope
gp120/gp41 complex (ENVelope glycoprotein). After gp120 shedding, gp41 is exposed
and elicits membrane fusion via a cascade of conformational changes. In contrast
to prefusion and postfusion conformation, little is known about any intermediate
conformation. We report on a solution NMR investigation of homotrimeric HIV-1
gp41(27-194), comprising the transmembrane region and reconstituted in dodecyl
phosphocholine (DPC) micelles. The protein is mainly alpha-helical, but
experiences internal dynamics on the nanosecond and micro to millisecond time
scale and transient alpha-helical behavior for certain residues in the N-terminal
heptad repeat (NHR). Strong lipid interactions are observed, in particular for C
terminal residues of the NHR and imunodominant loop region connecting NHR and C
terminal heptad repeat (CHR). Our data indicate an extended conformation with
features anticipated for a prefusion intermediate, presumably in exchange with a
lowly populated postfusion six-helical bundle conformation.
PMID- 25132086
TI - Synthesis, surface properties and antimicrobial activity of some germanium
nonionic surfactants.
AB - Esterification reaction between different fatty acid namely; lauric, stearic,
oleic and linoleic acids and polyethylene glycol-400 were performed. The produced
polyethylene glycol ester were reacted with p-amine benzoic acid followed by
condensation reaction with germanium dioxide in presence of sodium carbonate to
form desired germinate surfactants. The chemical structures of the synthesized
surfactants were determined using different spectra tools. The surface parameter
including: the critical micelle concentration (CMC), effectiveness (pi(cmc)),
efficiency (Pc20), maximum surface excess (Gamma(max)) and minimum surface area
(A(min)), were calculated from the surface tension measurements. The synthesized
surfactants showed higher surface activity. The thermodynamic parameters showed
that adsorption and micellization processes are spontaneous. It is clear that the
synthesized nonionic surfactants showed their tendency towards adsorption at the
interfaces and also micellization in the bulk of their solutions. The synthesized
surfactants were tested against different strain of bacteria using inhibition
zone diameters. The synthesized surfactants showed good antimicrobial activities
against the tested microorganisms including Gram positive, Gram negative as well
as fungi. The promising inhibition efficiency of these compounds against the
sulfate reducing bacteria facilitates them to be applicable as new categories of
sulfate reducing bacteria biocides.
PMID- 25132085
TI - Crystal structures of designed armadillo repeat proteins: implications of
construct design and crystallization conditions on overall structure.
AB - Designed armadillo repeat proteins (dArmRP) are promising modular proteins for
the engineering of binding molecules that recognize extended polypeptide chains.
We determined the structure of a dArmRP containing five internal repeats and 3rd
generation capping repeats in three different states by X-ray crystallography:
without N-terminal His6 -tag and in the presence of calcium (YM5 A/Ca(2+) ),
without N-terminal His6 -tag and in the absence of calcium (YM5 A), and with N
terminal His6 -tag and in the presence of calcium (His-YM5 A/Ca(2+)). All
structures show different quaternary structures and superhelical parameters. His
YM5 A/Ca(2+) forms a crystallographic dimer, which is bridged by the His6 -tag,
YM5 A/Ca(2+) forms a domain-swapped tetramer, and only in the absence of calcium
and the His6 -tag, YM5 A forms a monomer. The changes of superhelical parameters
are a consequence of calcium binding, because calcium ions interact with
negatively charged residues, which can also participate in the modulation of
helix dipole moments between adjacent repeats. These observations are important
for further optimizations of dArmRPs and provide a general illustration of how
construct design and crystallization conditions can influence the exact structure
of the investigated protein.
PMID- 25132084
TI - Structural mapping of divergent regions in the type 1 ryanodine receptor using
fluorescence resonance energy transfer.
AB - Ryanodine receptors (RyRs) release Ca(2+) to initiate striated muscle
contraction. Three highly divergent regions (DRs) in the RyR protein sequence
(DR1, DR2, and DR3) may confer isoform-specific functional properties to the
RyRs. We used cell-based fluorescence resonance energy transfer (FRET)
measurements to localize these DRs to the cryoelectron microscopic (cryo-EM) map
of the skeletal muscle RyR isoform (RyR1). FRET donors were targeted to RyR1
using five different FKBP12.6 variants labeled with Alexa Fluor 488. FRET was
then measured to the FRET acceptors, Cy3NTA or Cy5NTA, targeted to decahistidine
tags introduced within the DRs. DR2 and DR3 were localized to separate positions
within the "clamp" region of the RyR1 cryo-EM map, which is presumed to interface
with Cav1.1. DR1 was localized to the "handle" region, near the regulatory
calmodulin-binding site on the RyR. These localizations provide insights into the
roles of DRs in RyR allosteric regulation during excitation contraction coupling.
PMID- 25132087
TI - Influence of extraction techniques on physical-chemical characteristics and
volatile compounds of extra virgin olive oil.
AB - The purpose of this study was to investigate three types of extraction methods of
extra virgin olive oil (EVOO) from the same cultivar (Ortice olive cultivar):
traditional or pressing (T) system, decanter centrifugation (DC) system and a
patented horizontal axis decanter centrifugation (HADC) system. Oil samples were
subjected to chemical analyses: free acidity, peroxide value, ultraviolet light
absorption K232 and K270, total polyphenols, antioxidant capacity, volatile
compounds and olfactory characteristics by electronic nose. The two
centrifugation systems showed better free acidity and peroxides value but total
polyphenol content was particularly high in extra virgin olive oil produced by
patented HADC system. Same volatile substances that positively characterize the
oil aroma were found in higher amount in the two centrifugation systems, although
some differences have been detected between DC and HADC system, other were found
in higher amount in extra virgin olive oil produced by T system. The electronic
nose analysis confirmed these results, principal component analysis (PCA) and
correlation matrix showed the major differences between EVOO produced by T and
HADC system. Taken together the results showed that DC and HADC systems produce
EVOO with better characteristics than T system and patented HADC is the best
extraction system.
PMID- 25132088
TI - Hydrodistillation extraction time effect on essential oil yield, composition, and
bioactivity of coriander oil.
AB - Coriander (Coriandrum sativum L.) is a major essential oil crop grown throughout
the world. Coriander essential oil is extracted from coriander fruits via
hydrodistillation, with the industry using 180-240 min of distillation time (DT),
but the optimum DT for maximizing essential oil yield, composition of
constituents, and antioxidant activities are not known. This research was
conducted to determine the effect of DT on coriander oil yield, composition, and
bioactivity. The results show that essential oil yield at the shorter DT was low
and generally increased with increasing DT with the maximum yields achieved at DT
between 40 and 160 min. The concentrations of the low-boiling point essential oil
constituents: alpha-pinene, camphene, beta-pinene, myrcene, para-cymene,
limonene, and gamma-terpinene were higher at shorter DT (< 2.5 min) and decreased
with increasing DT; but the trend reversed for the high-boiling point
constituents: geraniol and geranyl-acetate. The concentration of the major
essential oil constituent, linalool, was 51% at DT 1.15 min, and increased
steadily to 68% with increasing DT. In conclusion, 40 min DT is sufficient to
maximize yield of essential oil; and different DT can be used to obtain essential
oil with differential composition. Its antioxidant capacity was affected by the
DT, with 20 and 240 min DT showing higher antioxidant activity. Comparisons of
coriander essential oil composition must consider the length of the DT.
PMID- 25132089
TI - Efficacy of concurrent cetuximab vs. 5-fluorouracil/carboplatin or high-dose
cisplatin with intensity-modulated radiation therapy (IMRT) for locally-advanced
head and neck cancer (LAHNSCC).
AB - OBJECTIVES: We previously reported inferior outcomes for locally-advanced head
and neck squamous cell carcinoma (LAHNSCC) patients treated with concurrent
cetuximab vs. high-dose cisplatin with intensity-modulated radiation therapy
(IMRT). Prior to FDA approval of cetuximab for LAHNSCC, non-cisplatin eligible
patients at our institution received 5-fluorouracil (5FU)/carboplatin. We sought
to compare concurrent cetuximab vs. 5FU/carboplatin vs. high-dose cisplatin with
IMRT for LAHNSCC. MATERIALS AND METHODS: Retrospective review was performed for
LAHNSCC patients treated at Memorial Sloan-Kettering Cancer Center from 11/02 to
04/08 with concurrent cetuximab (n=49), 5FU/carboplatin (n=52), or cisplatin
(n=259) and IMRT. Overall survival (OS), locoregional failure (LRF), distant
metastasis-free survival, and late toxicity were analyzed using univariate and
multivariate analyses. OS analysis was confirmed by propensity score adjustment.
RESULTS: Treatment groups were similar with regard to primary tumor site, overall
stage, and alcohol and tobacco history. Cetuximab and 5FU/carboplatin patients
were older, with lower performance status, more comorbidities, higher T
classification, and worse renal function. On multivariate analysis, compared with
cisplatin and 5FU/carboplatin, cetuximab was associated with inferior 4-year OS
(86.9% vs. 70.2% vs. 40.9%; P<.0001) and 4-year LRF (6.3% vs. 9.7% vs. 40.2%;
P<.0001). Late toxicity was highest with 5FU/carboplatin (25.0%) vs. cisplatin
(8.0%) vs. cetuximab (7.7%). CONCLUSIONS: Although 5FU/carboplatin patients were
sicker and experienced greater toxicity than cisplatin patients, no significant
difference was found in all endpoints. In contrast, despite similar pretreatment
characteristics, outcomes for cetuximab vs. 5FU/carboplatin were significantly
worse. We feel that caution should be used with routine use of cetuximab in the
management of LAHNSCC.
PMID- 25132090
TI - Association between oral leukoplakia and upper gastrointestinal cancers: a 28
year follow-up study in the Linxian General Population Trial.
AB - BACKGROUND: Oral leukoplakia is a precancerous disorder that is common among
residents in Linxian. However, the associations between oral leukoplakia and
upper gastrointestinal cancers have not been reported. We investigated the
relationships between oral leukoplakia and upper gastrointestinal cancers in the
Linxian General Population Trial cohort. METHODS: The Linxian General Population
Trial cohort, with 29,584 healthy adults enrolled in 1985 and followed through
the end of 2012. With collected baseline data, hazard ratios (HR) and 95%
confidence intervals (95% CI) for developing upper gastrointestinal cancers were
estimated using Cox proportional hazard models. RESULTS: During 28 years of
follow-up, we confirmed a total of 2924 incident esophageal squamous cell
carcinoma (ESCC) cases, 1644 gastric cardia cancers and 590 gastric non-cardia
cancers. Overall, participants with oral leukoplakia had significantly higher
risk of developing ESCC (HR=1.18, 95% CI: 1.08, 1.29). Among individuals ?52
years old at baseline, oral leukoplakia was associated with elevated risk of ESCC
(HR=1.31, 95%CI: 1.15, 1.49). No significant associations were observed for
gastric cardia or non-cardia cancers in either all subjects or subgroups.
CONCLUSIONS: Oral leukoplakia was associated with increased risk of ESCC,
particularly in younger population. Future studies are needed to confirm these
findings.
PMID- 25132092
TI - Rootstock-to-scion transfer of transgene-derived small interfering RNAs and their
effect on virus resistance in nontransgenic sweet cherry.
AB - Small interfering RNAs (siRNAs) are silencing signals in plants. Virus-resistant
transgenic rootstocks developed through siRNA-mediated gene silencing may enhance
virus resistance of nontransgenic scions via siRNAs transported from the
transgenic rootstocks. However, convincing evidence of rootstock-to-scion
movement of siRNAs of exogenous genes in woody plants is still lacking. To
determine whether exogenous siRNAs can be transferred, nontransgenic sweet cherry
(scions) was grafted on transgenic cherry rootstocks (TRs), which was transformed
with an RNA interference (RNAi) vector expressing short hairpin RNAs of the
genomic RNA3 of Prunus necrotic ringspot virus (PNRSV-hpRNA). Small RNA
sequencing was conducted using bud tissues of TRs and those of grafted
(rootstock/scion) trees, locating at about 1.2 m above the graft unions.
Comparison of the siRNA profiles revealed that the PNRSV-hpRNA was efficient in
producing siRNAs and eliminating PNRSV in the TRs. Furthermore, our study
confirmed, for the first time, the long-distance (1.2 m) transfer of PNRSV-hpRNA
derived siRNAs from the transgenic rootstock to the nontransgenic scion in woody
plants. Inoculation of nontransgenic scions with PNRSV revealed that the
transferred siRNAs enhanced PNRSV resistance of the scions grafted on the TRs.
Collectively, these findings provide the foundation for 'using transgenic
rootstocks to produce products of nontransgenic scions in fruit trees'.
PMID- 25132091
TI - Inhibition of H3K4me2 Demethylation Protects Auditory Hair Cells from Neomycin
Induced Apoptosis.
AB - Aminoglycoside-induced hair cell loss is a major cause of hearing impairment in
children and deserves more attention in medical research. Epigenetic mechanisms
have been shown to protect hair cells from ototoxic drugs. In this study, we
focused on the role of dimethylated histone H3K4 (H3K4me2) in hair cell survival.
To investigate the effects of lysine-specific demethylase 1 (LSD1)--the histone
demethylase primarily responsible for demethylating H3K4me2--on neomycin-induced
hair cell loss, isolated cochleae were pretreated with LSD1 inhibitors followed
by neomycin exposure. There was a severe loss of hair cells in the organ of Corti
after neomycin exposure, and inhibition of LSD1 significantly protected against
neomycin-induced hair cell loss. H3K4me2 expression in the nuclei of hair cells
decreased after exposure to neomycin, and blocking the decreased expression of
H3K4me2 with LSD1 inhibitors prevented hair cell loss. Local delivery of these
inhibitors in vivo also protected hair cells from neomycin-induced ototoxicity
and maintained the hearing threshold in mice as determined by auditory brain stem
response. This inhibition of neomycin-induced apoptosis occurs via reduced
caspase-3 activation. Together, our findings demonstrate the protective role for
H3K4me2 against neomycin-induced hair cell loss and hearing loss.
PMID- 25132093
TI - Positive effects of melatonin treatment on the reproductive performance of young
border leicester rams mated to merino ewes in spring: preliminary observations.
AB - Poor reproductive performance of Merino ewe flocks when mated to Border Leicester
rams during spring may be due to seasonality of the Border Leicester breed. Two
approaches were taken to test this assumption. Six young (12 months old) or six
mixed-age (12, 24 and >=36 months old) Border Leicester rams were either treated
or not treated with melatonin implants (2 * 2 design) 6 weeks before the four
groups of rams were each put with approximately 300 Merino ewes for an 8-week
mating period. Implants were inserted in early September (experiment 1). The
second approach was to yard or not yard ewes and mixed-age rams on several
occasions during the first 3 weeks of the mating period (experiment 2). Pregnancy
rate and twinning percentage were assessed by ultrasonography. In experiment 1,
melatonin treatment in young rams increased (p < 0.001) pregnancy rate from 5.0%
to 92.6%, but mixed-age rams did not respond (90.7% vs 89.5% for melatonin and
non-melatonin treatments, respectively). Twinning rate was similar (p > 0.05) for
ewes mated to either melatonin or non-melatonin-treated young rams (36.8% vs
40.0%, respectively), whereas melatonin significantly improved (p < 0.05)
twinning rate in those ewes mated to mixed-age rams (49.1% vs 36.1%). After 6
weeks of melatonin treatment, scrotal circumference was greater (p < 0.05) in
both young and mixed-aged rams than in untreated counterparts. In experiment 2,
yarding of ewes and rams overnight on several occasions early in the mating
period reduced (p < 0.001) pregnancy rate compared with non-yarded counterparts
(89.5% vs 65.5%). Twinning rate was not affected (37.7% vs 36.1%, respectively).
In summary, melatonin treatment of Border Leicester rams significantly improved
flock reproductive performance in spring due to improved pregnancy rates with
young rams and improved litter size with mixed-age rams.
PMID- 25132094
TI - Mucosal immunology: killing time in the lungs.
PMID- 25132096
TI - Pattern recognition receptors: curbing gut inflammation.
PMID- 25132097
TI - Incomplete bladder emptying is associated with febrile urinary tract infections
in infants.
AB - OBJECTIVE: To investigate lower urinary tract dysfunction in pre-toilet trained
infants with and without history of febrile UTI (f-UTI). MATERIALS AND METHODS:
Pre-toilet trained infants with f-UTI (Group 1) from pediatric nephrology and
urology clinics, and those without f-UTI (Group 2) from infant-care centers were
enrolled for the present study. Infants in Group 1 underwent four-hourly (4-H)
observations for at least one month after treatment for UTI. Voided volume (VV)
and post-void residual urine (PVR) were measured by weighting diaper and
suprapubic ultrasound after finishing voiding, respectively. Average PVR was
defined as the mean value of PVR during 4-H observation. Interrupted voiding was
defined as two or three voidings within 10 min. Voiding efficiency was defined as
VV/(VV+PVR). RESULTS: The mean ages of Group 1 (n=64) and Group 2 infants (n=56)
were 10.6+/-7.5 months vs 10.2+/-5.1 months, respectively (p=0.70). Group 1
infants had significantly higher voiding frequency (3.0 times+/-1.2 vs 2.6
times+/-0.9, p=0.04), average PVR (14.5 ml+/-14.2 vs 8.9 ml+/-8.8, p<0.01) and
lower voiding efficiency (71.2%+/-20.5 vs 80.2%+/-18.5, p=0.01) than Group 2. ROC
curve analysis showed that the optimal cutoff values for PVR and voiding
efficiency to differentiate Group 1 and Group 2 infants were 10 ml and 80%,
respectively. Group 1 infants had significantly more repeat elevated PVR (?10 ml)
and repeat low voiding efficiency (?80%) than Group 2 (44.8% vs 22.4%, p=0.03;
62.0% vs 28.6%, p<0.01, respectively). CONCLUSION: Pre-toilet trained infants
with f-UTI were associated with elevated PVR and lower voiding efficiency than
normal controls.
PMID- 25132095
TI - Interactions between innate and adaptive lymphocytes.
AB - Innate lymphocytes - including natural killer cells and the recently discovered
innate lymphoid cells - have crucial roles during infection, tissue injury and
inflammation. Innate signals regulate the activation and homeostasis of innate
lymphocytes. The contribution of the adaptive immune system to the coordination
of innate lymphocyte responses is less well understood. In this Opinion article,
we review our current understanding of the interactions between adaptive and
innate lymphocytes, and propose a model in which T cells of the adaptive immune
system function as antigen-specific sensors for the activation of innate
lymphocytes to amplify and instruct local immune responses. We highlight the
potential roles of regulatory and helper T cells in these processes, and discuss
major questions in the emerging area of crosstalk between adaptive and innate
lymphocytes.
PMID- 25132098
TI - Midwives' experiences of the factors that facilitate normal birth among low risk
women at a public hospital in Australia.
AB - BACKGROUND: normal birth has major advantages for mothers and infants.
Nonetheless, in the developed world, rates of normal birth have declined
significantly over the past 20 years, and many women currently have caesarean
section births for unclear reasons. Midwives are interested in ameliorating this
trend and aim to facilitate women to have meaningful birth experiences and to
achieve the best possible birth. OBJECTIVES: this project aimed to explore
midwives' experiences and views of the factors that facilitate or impede normal
birth. SETTING: one maternity setting in Melbourne, Australia. PARTICIPANTS: a
purposive sample of 22 midwives, all with recent birthing experience,
participated in in-depth interviews. METHODS: a qualitative study using an
Interpretative Phenomenological approach. Interviews were audio-recorded and
transcribed verbatim. Analysis was guided by Smith and Osborn's (2008) approach.
FINDINGS: midwives identified a number of factors that complicated their task of
facilitating normal birth. Barriers included: (1) time pressures; (2) a risk
adverse culture, and; (3) women's expectations. Factors facilitating normal birth
included: (1) a supporting environment, and (2) midwifery attributes and a desire
to promote normal birth. KEY CONCLUSIONS: in Australia, most births take place in
obstetric models of care, in which the majority of midwives are employed. The
birth environment, in these units, is often risk-adverse with high rates of
intervention and caesarean section. Midwives, wishing to promote normal birth in
obstetric led units, face a number of challenges and often feel unsupported by
senior colleagues. This situation causes conflict and gives rise to stress and
unmet support needs.
PMID- 25132099
TI - Effect of Lys656Asn Polymorphism of Leptin Receptor Gene on Cardiovascular Risk
Factors and Serum Adipokine Levels after a High Polyunsaturated Fat Diet in Obese
Patients.
AB - BACKGROUND: Human obesity is characterized by high levels of leptin, and leptin
levels may change with weight loss and dietary restriction. The aim of our study
was to investigate the influence of Lys656Asn polymorphism in the leptin receptor
gene on cardiovascular risk factors, weight loss, and serum leptin levels to a
high polyunsaturated fatty acid (PUFA) hypocaloric diet in obese patients.
DESIGN: A sample of 132 obese patients was analyzed in a prospective way with a
dietary intervention. The enriched PUFAs hypocaloric intervention consisted in a
diet of 1,459 kcal, 45.7% of carbohydrates, 34.4% of lipids, and 19.9% of
proteins. RESULTS: In wild-type group, BMI (-1.9 +/- 1.4 kg/m(2) ), weight (-4.4
+/- 3.2 kg), fat mass (-4.2 +/- 3.8 kg), waist circumference (-4.1 +/- 3.1 cm),
systolic blood pressure (-7.0 +/- 12.1 mmHg), diastolic blood pressure (-3.9 +/-
6.8 mmHg), insulin (-1.8 +/- 5.6 MUI/l) and HOMA-IR (-0.5 +/- 1.5 Units)
decreased. In mutant genotype group, BMI (-2.0 +/- 2.1 kg/m(2) ), weight (-3.6 +/
4.1 kg), waist circumference (-3.1 +/- 4.1 cm), total cholesterol (-25.2 +/-
19.6 mg/dl), LDL cholesterol (-16.6 +/- 25.6 mg/dl), and tryglicerides (-26.6 +/-
39.1 mg/dl) decreased. Only leptin levels have a significant decrease in wild
genotype group (-6.6 +/- 10.2 ng/ml) (25.1%). CONCLUSION: Carriers of ASn656
allele have a different response than wild-type obese, with a lack of decrease in
insulin levels, leptin levels, and HOMA-IR. However, obese patients with this
mutant allele have a better lipid profile after weight loss.
PMID- 25132100
TI - Hypertension triggers the rupture of coronary artery aneurysm in an 8-year-old
boy with Kawasaki disease.
PMID- 25132101
TI - Assessment of ovarian activity in captive goral (Naemorhedus griseus) using
noninvasive fecal steroid monitoring.
AB - To date, there is no information on gonadal steroidogenic activity of female
goral (Naemorhedus griseus), a threatened species of Thailand. Captive goral
populations have been established to produce animals for ex situ conservation and
reintroduction, but as yet none are self-sustaining. The objectives of the
present study were to (1) determine the influence of season on ovarian
steriodogenic function; and (2) examine the relationship between gonadal hormone
excretion and sexual behaviors throughout the year. Fecal samples were collected
5 to 7 days/wk for 15 months from 8 adult females housed at Omkoi Wildlife
Breeding Center in Thailand and analyzed for ovarian steroid metabolites using
validated enzyme immunoassays. Observations of sexual behaviors and mating were
conducted each morning for 30 min/session. Based on fecal estrogen and
progestagen metabolite concentrations, the overall estrous cycle length was about
21 days, with a 2- to 3-day follicular phase and an 18- to 20-day luteal phase.
Sexual behaviors, most notably tail-up, increased for 2 to 3 days during the time
estrogens were elevated during mating. Fecal progestagens were elevated during
luteal phases and increased further during gestation, which lasted approximately
7 months. The lactation period was 5 months, and females were anestrus for 2 to 5
of those months, with the exception of one that cycled continuously throughout.
Two females conceived around 2 months postpartum and so were pregnant during
lactation. Birth records over the past 21 years indicated young are born
throughout the year. This combined with the hormonal data suggests that female
gorals are not strongly seasonal, at least in captivity, although there was
considerable variation among females in estrogen and progestagen patterns. In
conclusion, fecal steroid metabolite monitoring is an effective means of
assessing ovarian function in this species and will be a useful tool for breeding
management and planned development of assisted reproductive techniques such as
artificial insemination and embryo transfer.
PMID- 25132102
TI - Expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins in human
retinoblastoma.
AB - BACKGROUND: Regulation of apoptosis is a complex process that involves a number
of genes, including Bcl-2, Bcl-x, Bax and other Bcl-2 family members. The aim of
the present study is to assess the expression of Bcl- 2 and Bax in
retinoblastoma, and correlate them with clinical and histopathological
parameters. METHODS: The expression of Bcl-2 and Bax proteins were examined using
immunohistochemistry, Western blotting and reverse transcriptase-polymerase chain
reaction in a series of 60 prospective cases of primary retinoblastoma tissues.
RESULTS: Immunohistochemistry showed expression of Bcl-2 in 40/60 (66.6%),
whereas Bax expression was found only in 18/60 (30%) cases, and these correlated
with mRNA expression. The Western blotting results also correlated well with the
immunohistochemical expression of Bcl-2 (25 kDa) and Bax (21 kDa) proteins. Bcl-2
was expressed in 96% (24/25) of invasive tumours and in 45.7% (16/35) of non
invasive tumours. Expression of Bcl-2 significantly correlated with tumour
invasiveness (P = 0.0274) and poor differentiation (P = 0.0163), whereas loss of
Bax correlated with massive choroidal invasion and Pathological Tumor-Node
Metastasis (pTNM) (P = 0.0341). However, no correlation was found between Bax and
Bcl-2 expression. CONCLUSIONS: Our findings suggest that these apoptotic
regulatory proteins may serve as poor prognostic markers and can be used as a
therapeutic target for the treatment of invasive retinoblastoma. Further
functional studies are required to explore the role of Bax and Bcl-2 in
retinoblastoma.
PMID- 25132103
TI - Brief report: complement C5a promotes human embryonic stem cell pluripotency in
the absence of FGF2.
AB - The complement activation product, C5a, is a pivotal member of the innate immune
response; however, a diverse number of nonimmune functions are now being ascribed
to C5a signaling, including roles during embryonic development. Here, we identify
the expression of the C5a precursor protein, C5, as well as the C5a receptors,
C5aR and C5L2, in both human embryonic stem cells and human-induced pluripotent
stem cells. We show that administration of a physiologically relevant dose of
purified human C5a (1 nM) stimulates activation of ERK1/2 and AKT signaling
pathways, and is able to promote maintenance of the pluripotent state in the
absence of FGF2. C5a also reduced cell loss following dissociation of human
pluripotent stem cells. Our results reveal that complement C5a signaling supports
human stem cell pluripotency and survival, and thus may play a key role in
shaping early human embryonic development.
PMID- 25132104
TI - Mechanism-specific effects of adenosine on ventricular tachycardia.
AB - INTRODUCTION: There is no universally accepted method by which to diagnose
clinical ventricular tachycardia (VT) due to cAMP-mediated triggered activity.
Based on cellular and clinical data, adenosine termination of VT is thought to be
consistent with a diagnosis of triggered activity. However, a major gap in
evidence mitigates the validity of this proposal, namely, defining the
specificity of adenosine response in well-delineated reentrant VT circuits. To
this end, we systematically studied the effects of adenosine in a model of canine
reentrant VT and in human reentrant VT, confirmed by 3-dimensional, pace- and
substrate mapping. METHODS AND RESULTS: Adenosine (12 mg [IQR 12-24]) failed to
terminate VT in 31 of 31 patients with reentrant VT due to structural heart
disease, and had no effect on VT cycle length (age, 67 years [IQR 53-74]);
ejection fraction, 35% [IQR 20-55]). In contrast, adenosine terminated VT in 45
of 50 (90%) patients with sustained focal right or left outflow tract
tachycardia. The sensitivity of adenosine for identifying VT due to triggered
activity was 90% (95% CI, 0.78-0.97) and its specificity was 100% (95% CI, 0.89
1.0). Additionally, reentrant circuits were mapped in the epicardial border zone
of 4-day-old infarcts in mongrel dogs. Adenosine (300-400 MUg/kg) did not
terminate sustained VT or have any effect on VT cycle length. CONCLUSION: These
data support the concept that adenosine's effects on ventricular myocardium are
mechanism specific, such that termination of VT in response to adenosine is
diagnostic of cAMP-mediated triggered activity.
PMID- 25132105
TI - Air pollution and emergency department visits for epistaxis.
AB - OBJECTIVES: This study aimed to evaluate the association between outdoor ambient
air pollution and emergency department (ED) visits for epistaxis. DESIGN: Cross
sectional study, case-crossover design. SETTING: ED visit data were obtained for
Edmonton, Alberta, Canada, for a period of 10 years starting 1 April 1992 and
ending March 31st of 2002. The data on ED visits were supplied by Capital Health
for the five major acute care hospitals in the Edmonton area. PARTICIPANTS: The
analysis was performed for the population as a whole (N = 15 038) and split by
sex: males (N = 8587) and females (N = 6451). MAIN OUTCOME MEASURES: We explored
associations between ambient concentrations of air pollutants (CO, NO2 , SO2 , O3
, PM10 , PM2.5 ) lagged by 0-4 days and ED visits for epistaxis in Edmonton,
Alberta, Canada. RESULTS: Odds ratios (ORs) and their 95% confidence intervals
(CI) were reported for an increase in an interquartile range (IQR) of pollutant
concentration. We obtained positive and statistically significant results for all
patients with epistaxis; exposure to O3 with IQR = 14 ppb, OR = 1.05 (95% CI:
1.00-1.09, lag 0), and for males (age < 25 years), OR = 1.16 (1.03-1.30), lag 4;
and to PM10 with IQR = 15 MUg/m(3) , OR = 1.02 (1.00-1.05, lag 3). These results
were stronger for older (age > 24 years) females. CONCLUSIONS: These findings
suggest that there may be an association between air pollutant exposure,
specifically ozone and PM10 , and the number of ED visits for epistaxis.
PMID- 25132106
TI - Subluminescence photodynamic therapy of recalcitrant foot warts.
PMID- 25132107
TI - FrxA is an S-nitrosoglutathione reductase enzyme that contributes to Helicobacter
pylori pathogenicity.
AB - Helicobacter pylori is a pathogen that infects the gastric mucosa of a large
percentage of the human population worldwide, and predisposes to peptic
ulceration and gastric cancer. Persistent colonization of humans by H. pylori
triggers an inflammatory response that leads to the production of reactive
nitrogen species. However, the mechanisms of H. pylori defence against
nitrosative stress remain largely unknown. In this study, we show that the NADH
flavin oxidoreductase FrxA of H. pylori, besides metabolizing nitrofurans and
metronidazole, has S-nitrosoglutathione reductase activity. In agreement with
this, inactivation of the FrxA-encoding gene resulted in a strain that was more
sensitive to S-nitrosoglutathione. FrxA was also shown to contribute to the
proliferation of H. pylori in macrophages, which are key phagocytic cells of the
mammalian innate immune system. Moreover, FrxA was shown to support the virulence
of the pathogen upon mouse infection. Altogether, we provide evidence for a new
function of FrxA that contributes to the successful chronic colonization ability
that characterizes H. pylori.
PMID- 25132108
TI - Efficient solar cells sensitized by porphyrins with an extended conjugation
framework and a carbazole donor: from molecular design to cosensitization.
AB - Porphyrin dyes containing the carbazole electron donor have been designed and
optimized by wrapping the porphyrin framework, introducing an additional
ethynylene bridge to extend the wavelength range of light absorption, and further
suppression of the dye aggregation by introducing additional alkoxy chains.
Application of a cosensitization approach results in improved current density
(Jsc) and open-circuit voltage (Voc) values, thus achieving the highest cell
efficiency of 10.45%. This work provides an effective combined strategy of
molecular design and cosensitization for developing efficient dye-sensitized
solar cells (DSSCs). In addition, carbazole has been demonstrated to be a
promising donor for porphyrin sensitizers.
PMID- 25132109
TI - New insights into HLA-G mediated tolerance.
AB - Human Leukocyte Antigen G (HLA-G) is a nonclassical HLA class I molecule with
well-characterized immunomodulatory activities. HLA-G was first described as a
regulatory molecule that allows the fetus to elude the maternal immune response.
In the last decade it has become evident that HLA-G is involved in modulating
both innate and adaptive immune responses, in maintaining tolerance in autoimmune
and inflammatory diseases and after transplantation, and in promoting immune
escape in cancer and infectious diseases. HLA-G exerts its modulatory/regulatory
functions directly by interacting with specific inhibitory receptors. The
expression of HLA-G is finely tuned by genetic variations in the noncoding region
of the locus. The recent discovery of dendritic cells-10 (DC-10) as naturally
occurring HLA-G-expressing dendritic cells opens new perspectives in the
identification of the molecular and cellular mechanisms underlying HLA-G-mediated
tolerance. An overview on the HLA-G-mediated inhibition of innate and adaptive
immune cells, on the genetic influence on HLA-G expression, and on HLA-G
expressing DC-10 is presented. Moreover, we discuss the central and critical role
of DC-10 in the HLA-G-mediated tolerance.
PMID- 25132110
TI - Urine sample preparation for proteomic analysis.
AB - Sample preparation for both environmental and more importantly biological
matrices is a bottleneck of all kinds of analytical processes. In the case of
proteomic analysis this element is even more important due to the amount of cross
reactions that should be taken into consideration. The incorporation of new post
translational modifications, protein hydrolysis, or even its degradation is
possible as side effects of proteins sample processing. If protocols are
evaluated appropriately, then identification of such proteins does not bring
difficulties. However, if structural changes are provided without sufficient
attention then protein sequence coverage will be reduced or even identification
of such proteins could be impossible. This review summarizes obstacles and
achievements in protein sample preparation of urine for proteome analysis using
different tools for mass spectrometry analysis. The main aim is to present
comprehensively the idea of urine application as a valuable matrix. This article
is dedicated to sample preparation and application of urine mainly in novel
cancer biomarkers discovery.
PMID- 25132111
TI - Predictors of psychological functioning in children with cancer: disposition and
cumulative life stressors.
AB - OBJECTIVE: This study examined psychological functioning in children with a
history of cancer and a matched sample of healthy peers, while exploring the
roles of disposition and stressful life events. METHOD: Participants were 255
children with a history of cancer and 101 demographically matched children (8-17
years). Children completed measures of depression, anxiety, and posttraumatic
stress symptoms (PTSS); history of stressful life events; and dispositional
factors, including optimism and a five-factor personality measure. RESULTS:
Children with cancer did not differ from peers with regard to depression and
PTSS, but reported significantly lower anxiety. In hierarchical regressions,
children's depression, anxiety, and PTSS scores were largely predicted by
dispositional variables and, to a lesser extent, stressful life events, after
controlling for demographics and health status. CONCLUSION: Children's
psychological functioning is predicted primarily by disposition, and secondarily
by history of stressful life events, with health status (i.e., cancer versus
control) accounting for minimal, and often non-significant variance in children's
functioning. These findings further support that children with cancer are
generally resilient, with factors predictive of their adjustment difficulties
mirroring those of children without history of serious illness.
PMID- 25132112
TI - Eugenia punicifolia (Kunth) DC. as an adjuvant treatment for type-2 diabetes
mellitus: a non-controlled, pilot study.
AB - Type-2 diabetes mellitus (DM) is a highly prevalent disease with significant
morbidity and mortality around the world. However, there is no universally
effective treatment, because response to different treatment regimens can vary
widely among patients. In this study, we aimed to investigate whether the use of
the powdered dried leaves of Eugenia punicifolia (Kunth) DC. (Myrtaceae) is
effective as an adjuvant to the treatment of patients with type-2 DM. Fifteen
patients were enrolled in a pilot, non-controlled study, and received E.
punicifolia for 3 months. After treatment, we observed a significant decrease in
glycosylated hemoglobin, basal insulin, thyroid-stimulating hormone, C-reactive
protein, and both systolic and diastolic blood pressure. There were no changes in
fasting and postprandial glycemia. The compounds myricetin-3-O-rhamnoside,
quercetin-3-O-galactoside, quercetin-3-O-xyloside, quercetin-3-O-rhamnoside,
kaempferol-3-O-rhamnoside, phytol, gallic acid, and trans-caryophyllene present
in the powdered dried leaves of E. punicifolia may be responsible for the
therapeutic effect. In conclusion, the powdered leaves of E. punicifolia are
promising as an adjuvant in the treatment of type-2 DM and deserve further
investigation.
PMID- 25132113
TI - Quantification of the statistical effects of spatiotemporal processing of nontask
FMRI data.
AB - Nontask functional magnetic resonance imaging (fMRI) has become one of the most
popular noninvasive areas of brain mapping research for neuroscientists. In
nontask fMRI, various sources of "noise" corrupt the measured blood oxygenation
level-dependent signal. Many studies have aimed to attenuate the noise in
reconstructed voxel measurements through spatial and temporal processing
operations. While these solutions make the data more "appealing," many commonly
used processing operations induce artificial correlations in the acquired data.
As such, it becomes increasingly more difficult to derive the true underlying
covariance structure once the data have been processed. As the goal of nontask
fMRI studies is to determine, utilize, and analyze the true covariance structure
of acquired data, such processing can lead to inaccurate and misleading
conclusions drawn from the data if they are unaccounted for in the final
connectivity analysis. In this article, we develop a framework that represents
the spatiotemporal processing and reconstruction operations as linear operators,
providing a means of precisely quantifying the correlations induced or modified
by such processing rather than by performing lengthy Monte Carlo simulations. A
framework of this kind allows one to appropriately model the statistical
properties of the processed data, optimize the data processing pipeline,
characterize excessive processing, and draw more accurate functional connectivity
conclusions.
PMID- 25132114
TI - Modeling nonlinear relationships in ERP data using mixed-effects regression with
R examples.
AB - In the analysis of psychological and psychophysiological data, the relationship
between two variables is often assumed to be a straight line. This may be due to
the prevalence of the general linear model in data analysis in these fields,
which makes this assumption implicitly. However, there are many problems for
which this assumption does not hold. In this paper, we show that, in the analysis
of event-related potential (ERP) data, the assumption of linearity comes at a
cost and may significantly affect the inferences drawn from the data. We
demonstrate why the assumption of linearity should be relaxed and how to model
nonlinear relationships between ERP amplitudes and predictor variables within the
familiar framework of generalized linear models, using regression splines and
mixed-effects modeling.
PMID- 25132115
TI - OMIP-023: 10-color, 13 antibody panel for in-depth phenotyping of human
peripheral blood leukocytes.
PMID- 25132116
TI - Selective TRAIL-induced cytotoxicity to lung cancer cells mediated by miRNA
response elements.
AB - Lung cancer is among the most common cancers, and the current therapeutic
strategies are still inefficient in most cases. Tumour necrosis factor-related
apoptosis-inducing ligand (TRAIL) is a promising biological agent for cancer
treatment because of its potent pro-apoptotic effect on cancer cells. However,
TRAIL also induces apoptosis in normal cells and therefore may cause toxicity to
normal tissues if clinically applied. To address this issue, we inserted microRNA
response elements (MREs) of miR-133a, miR-137 and miR-449a, which are all
underexpressed in lung cancer cells, into an adenoviral vector to regulate TRAIL
expression. This MRE-regulated vector (Ad-TRAIL-MRE) was able to express TRAIL in
a lung-cancer-specific fashion. No TRAIL expression was detected in normal cells.
Consistently, Ad-TRAIL-MRE exerted cytotoxicity to lung cancer cells, rather than
normal cells, perhaps via inducing selective apoptosis. The selective TRAIL
mediated growth-inhibiting effect was further confirmed in a tumour xenograft
model. Also, Ad-TRAIL-MRE only resulted in very low hepatotoxicity when applied.
Collectively, we generated a novel TRAIL-expressing adenoviral vector that was
regulated by MREs. This strategy permits TRAIL expression in a lung-cancer
specific manner and is worth further studying for clinical trials.
PMID- 25132117
TI - Meta-analysis of the effect of postoperative in-hospital morbidity on long-term
patient survival.
AB - BACKGROUND: Major surgery is associated with high rates of postoperative
complications, many of which are deemed preventable. It has been suggested that
these complications not only present a risk to patients in the short term, but
may also reduce long-term survival. The aim of this review was to examine the
effects of postoperative complications on long-term survival. METHODS: MEDLINE,
Web of Science and reference lists of relevant articles were searched up to July
2013. Studies assessing only procedure-specific, or technical failure-related,
complications were excluded, as were studies of poor methodological quality. Meta
analysis was performed using a random-effects model. Risk of bias was assessed
using funnel plots. RESULTS: Eighteen eligible studies were included, comprising
results for 134 785 patients with an overall complication rate of 22.6 (range
10.6-69) per cent. The studies included operations for both benign and malignant
disease. Median follow-up was 43 (range 28-96) months. Meta-analysis demonstrated
reduced overall survival after any postoperative complication for ten studies
with eligible data (20 755 patients), with a hazard ratio (HR) of 1.28 (95 per
cent confidence interval 1.21 to 1.34). Similar results were found for overall
survival following infectious complications: HR 1.92 (1.50 to 2.35). In analyses
of disease-free survival the HR was 1.26 (1.10 to 1.42) for all postoperative
complications and 1.55 (1.12 to 1.99) for infectious complications. Inclusion of
poor-quality studies in a sensitivity analysis had no effect on the results.
CONCLUSION: Postoperative complications have a negative effect on long-term
survival. This relationship appears to be stronger for infectious complications.
PMID- 25132118
TI - Neuroprotective peptide-macrocycle conjugates reveal complex structure-activity
relationships in their interactions with amyloid beta.
AB - Interactions between amyloid beta (Abeta) and metal ions are thought to mediate
the neuropathogenic effects of Abeta in Alzheimer's disease. The construction of
small molecules capable of synergistically chelating metal ions and recognizing
Abeta would allow new insights into the biology of this disease and provide a
possible therapeutic approach. We report herein the synthesis and biological
evaluation of tetraazamacrocycle-(G)KLVFF hybrids and their metal complexes. The
results obtained from ThT and bis-ANS extrinsic fluorescence assays, tyrosine
intrinsic fluorescence assay and proteolytic assay imply complex, multifaceted
structure-activity relationships in the interaction of these conjugates with
Abeta. Many of the compounds tested rescued cells from Abeta-induced
cytotoxicity. The attendant simplicity and ready diversification of the synthesis
of these conjugates makes them attractive for further investigation.
PMID- 25132120
TI - Snacks, beverages, vending machines, and school stores: a comparison of
alternative and regular schools in Minnesota, 2002 to 2008.
AB - In US secondary schools, vending machines and school stores are a common source
of low-nutrient, energy-dense snacks and beverages, including sugar-sweetened
beverages, high-fat salty snacks, and candy. However, little is known about the
prevalence of these food practices in alternative schools, which are educational
settings for students at risk of academic failure due to truancy, school
expulsion, and behavior problems. Nationwide, more than 5,000 alternative schools
enroll about one-half million students who are disproportionately minority and
low-income youth. Principal survey data from a cross-sectional sample of
alternative (n=104) and regular (n=339) schools collected biennially from 2002
2008 as part of the Centers for Disease Control and Prevention Minnesota School
Health Profiles were used to assess and compare food practice prevalence over
time. Generalized estimating equation models were used to estimate prevalence,
adjusting for school demographics. Over time, food practice prevalence decreased
significantly for both alternative and regular schools, although declines were
mostly modest. However, the decrease in high-fat, salty snacks was significantly
less for alternative than regular schools (-22.9% vs -42.2%; P<0.0001). Efforts
to improve access to healthy food choices at school should reach all schools,
including alternative schools. Study findings suggest high-fat salty snacks are
more common in vending machines and school stores in alternative schools than
regular schools, which may contribute to increased snacking behavior among
students and extra consumption of salt, fat, and sugar. Study findings support
the need to include alternative schools in future efforts that aim to reform the
school food environment.
PMID- 25132119
TI - Attenuated improvements in adiponectin and fat loss characterize type 2 diabetes
non-remission status after bariatric surgery.
AB - AIM: To identify the metabolic determinants of type 2 diabetes non-remission
status after bariatric surgery at 12 and 24 months. METHODS: A total of 40 adults
[mean +/- sd body mass index 36 +/- 3 kg/m(2) , age 48 +/- 9 years, glycated
haemoglobin (HbA1c) 9.7 +/- 2%) undergoing bariatric surgery [Roux-en-Y gastric
bypass (RYGB) or sleeve gastrectomy (SG)] were enrolled in the present study, the
Surgical Treatment and Medication Potentially Eradicate Diabetes Efficiently
(STAMPEDE) trial. Type 2 diabetes remission was defined as HbA1c <6.5% and
fasting glucose <126 mg/dl (i.e. <7 mmol/l) without antidiabetic medication.
Indices of insulin secretion and sensitivity were calculated from plasma glucose,
insulin and C-peptide values during a 120-min mixed-meal tolerance test. Body
fat, incretins (glucagon-like polypeptide-1, gastric inhibitory peptide, ghrelin)
and adipokines [adiponectin, leptin, tumour necrosis factor-alpha, high
sensitivity C-reactive protein (hs-CRP)] were also assessed. RESULTS: At 24
months, 37 patients had available follow-up data (RYGB, n = 18; SG, n = 19).
Bariatric surgery induced type 2 diabetes remission rates of 40 and 27% at 12 and
24 months, respectively. Total fat/abdominal fat loss, insulin secretion, insulin
sensitivity and beta-cell function (C-peptide0-120 /glucose0-120 * Matsuda index)
improved more in those with remission at 12 and 24 months than in those without
remission. Incretin levels were unrelated to type 2 diabetes remission, but,
compared with those without remission, hs-CRP decreased and adiponectin increased
more in those with remission. Only baseline adiponectin level predicted lower
HbA1c levels at 12 and 24 months, and elevated adiponectin correlated with
enhanced beta-cell function, lower triglyceride levels and fat loss. CONCLUSIONS:
Smaller rises in adiponectin level, a mediator of insulin action and adipose
mass, characterize type 2 diabetes non-remission up to 2 years after bariatric
surgery. Adjunctive strategies promoting greater fat loss and/or raising
adiponectin may be key to achieving higher type 2 diabetes remission rates after
bariatric surgery.
PMID- 25132121
TI - Misreporting of dietary intake affects estimated nutrient intakes in low-income
Spanish-speaking women.
AB - Misreporting of dietary intake affects the validity of data collected and
conclusions drawn in studies exploring diet and health outcomes. One consequence
of misreporting is biological implausibility. Little is known regarding how
accounting for biological implausibility of reported intake affects nutrient
intake estimates in Hispanics, a rapidly growing demographic in the United
States. Our study explores the effect of accounting for plausibility on nutrient
intake estimates in a sample of Mexican-American women in northern California in
2008. Nutrient intakes are compared with Dietary Reference Intake
recommendations, and intakes of Mexican-American women in a national survey are
presented as a reference. Eighty-two women provided three 24-hour recalls.
Reported energy intakes were classified as biologically plausible or implausible
using the reported energy intakes to total energy expenditure cutoff of <0.76 or
>1.24, with low-active physical activity levels used to estimate total energy
expenditure. Differences in the means of nutrient intakes between implausible
(n=36) and plausible (n=46) reporters of energy intake were examined by bivariate
linear regression. Estimated energy, protein, cholesterol, dietary fiber, and
vitamin E intakes were significantly higher in plausible reporters than
implausible. There was a significant difference between the proportions of
plausible vs implausible reporters meeting recommendations for several nutrients,
with a larger proportion of plausible reporters meeting recommendations. Further
research related to misreporting in Hispanic populations is warranted to explore
the causes and effects of misreporting in studies measuring dietary intake, as
well as actions to be taken to prevent or account for this issue.
PMID- 25132122
TI - The effect of nopal (Opuntia ficus indica) on postprandial blood glucose,
incretins, and antioxidant activity in Mexican patients with type 2 diabetes
after consumption of two different composition breakfasts.
AB - Nopal is a plant used in traditional Mexican medicine to treat diabetes. However,
there is insufficient scientific evidence to demonstrate whether nopal can
regulate postprandial glucose. The purpose for conducting this study was to
evaluate the glycemic index, insulinemic index, glucose-dependent insulinotropic
peptide (GIP) index, and the glucagon-like peptide 1 (GLP-1) index, and the
effect of nopal on patients with type 2 diabetes after consumption of a high
carbohydrate breakfast (HCB) or high-soy-protein breakfast (HSPB) on the
postprandial response of glucose, insulin, GIP, GLP-1, and antioxidant activity.
In study 1, the glycemic index, insulinemic index, GIP index, and GLP-1 index
were calculated for seven healthy participants who consumed 50 g of available
carbohydrates from glucose or dehydrated nopal. In study 2, 14 patients with type
2 diabetes consumed nopal in HCB or HSPB with or without 300 g steamed nopal. The
glycemic index of nopal was 32.5+/-4, insulinemic index was 36.1+/-6, GIP index
was 6.5+/-3.0, and GLP-1 index was 25.9+/-18. For those patients with type 2
diabetes who consumed the HCB+nopal, there was significantly lower area under the
curve for glucose (287+/-30) than for those who consumed the HCB only (443+/-49),
and lower incremental area under the curve for insulin (5,952+/-833 vs 7,313+/
1,090), and those patients with type 2 diabetes who consumed the HSPB avoided
postprandial blood glucose peaks. Consumption of the HSPB+nopal significantly
reduced the postprandial peaks of GIP concentration at 30 and 45 minutes and
increased the antioxidant activity after 2 hours measured by the 2,2-diphenyl-1
picrilhidracyl method. These findings suggest that nopal could reduce
postprandial blood glucose, serum insulin, and plasma GIP peaks, as well as
increase antioxidant activity in healthy people and patients with type 2
diabetes.
PMID- 25132123
TI - Scoring of international criteria for Behcet's disease.
PMID- 25132125
TI - Different responses of the melanin index to ultraviolet irradiation in relation
to skin color and body site.
AB - BACKGROUND/PURPOSE: Few reports describe UVB irradiation-induced pigmentation
responses from different skin colors or from different body sites. This study
determined pigmentation changes in skin with different colors and from different
body sites following 308-nm excimer laser irradiation. METHODS: Ten healthy
Korean adults were divided into light- and dark-skin groups, and irradiated body
sites were divided into unexposed zones (UZ), intermittently exposed zones (IEZ),
and frequently exposed zones (FEZ). Twenty-four areas were irradiated with a
single 300-mJ/cm(2) shot delivered by an excimer laser. MIs were measured before
irradiation, immediately after irradiation, and then 1 day, 3 days, 7 days, 14
days, and 21 days after irradiation. RESULTS: MIs declined significantly on day 1
after irradiation, particularly in light-colored skin. In the light-skin group,
the MI increased from day 3 after irradiation and continued to increase for 21
days, whereas in the dark-skin group, the peak MI was reached at 7 days and
declined thereafter. The peak MIs were reached at 7 days in the IEZ and FEZ and
at 14 days in the UZ. CONCLUSION: Following UVB irradiation, MIs decreased,
particularly in light-colored skin, before delayed tanning developed. UVB-induced
pigmentation varied according to different skin colors and the body sites
irradiated.
PMID- 25132124
TI - Barriers to and incentives for achieving partograph use in obstetric practice in
low- and middle-income countries: a systematic review.
AB - BACKGROUND: The partograph is a graphic display of the progress of labour,
recommended by the World Health Organization, but often underused in practice in
low- and middle-income countries. We were interested in going beyond
demonstration of potential efficacy - on which the existing literature
concentrates - through a systematic review to identify barriers to and incentives
for achieving partograph use. METHODS: We searched Ovid MEDLINE, Ovid Maternity
and Infant Care, POPLINE, Web of Science, and Scopus, from 1st January 1994 to
30th September 2013, using the term 'partogra*' to include 'partograph',
'partogram', or 'partogramme'. The selection criteria were for primary or
secondary research describing barriers to and incentives for partograph use in
low- and middle-income countries, in English, reported in peer-reviewed
publications since 1994. Thematic analysis of text on partograph use was applied
to a commonly used framework for change in clinical practice, with levels
describing the innovation, the individual professional, the woman, and social,
organisational, economic and political contexts. RESULTS: Reported barriers to
and incentives for partograph use related to the partograph itself, professional
skills and practice, clinical leadership and quality assurance, and the
organisational environment within the wider provision of obstetric care. Neither
the evidence base for its effectiveness, nor its credibility, was reported as a
barrier to use. CONCLUSION: Identifying and addressing local barriers and
incentives in low- and middle-income countries, based on those in published
research, could inform strategies to improve partograph use. Emerging
technologies could be used to address some barriers. The thresholds for essential
maternity care at which the partograph adds value should be further evaluated.
PMID- 25132126
TI - Reconstructing the colonization history of lost wolf lineages by the analysis of
the mitochondrial genome.
AB - The grey wolves (Canis lupus) originally inhabited major parts of the Northern
hemisphere, but many local populations became extinct. Two lineages of wolves in
Japan, namely, Japanese or Honshu (C. l. hodophilax) and Ezo or Hokkaido (C. l.
hattai) wolves, rapidly went extinct between 100 and 120years ago. Here we
analyse the complete mitochondrial genome sequences from ancient specimens and
reconstruct the colonization history of the two extinct subspecies. We show a
unique status of Japanese wolves in wolf phylogeny, suggesting their long time
separation from other grey wolf populations. Japanese wolves appeared to have
colonized the Japanese archipelago in the Late Pleistocene (ca. 25,000
125,000years ago). By contrast, Ezo wolves, which are clearly separated from
Japanese wolves in phylogeny, are likely to have arrived at Japan relatively
recently (<14,000years ago). Interestingly, their colonization history to Japan
tallies well with the dynamics of wolf populations in Europe and America during
the last several millennia. Our analyses suggest that at least several thousands
of wolves once inhabited in the Japanese archipelago. Our analyses also show that
an enigmatic clade of domestic dogs is likely to have originated from rare
admixture events between male dogs and female Japanese wolves.
PMID- 25132127
TI - Metapopulations in temporary streams - the role of drought-flood cycles in
promoting high genetic diversity in a critically endangered freshwater fish and
its consequences for the future.
AB - Genetic factors have direct and indirect impacts in the viability of endangered
species. Assessing their genetic diversity levels and population structure is
thus fundamental for conservation and management. In this paper we use
mitochondrial and nuclear markers to address phylogeographic and demographic data
on the critically endangered Anaecypris hispanica, using a broad sampling set
which covered its known distribution area in the Iberian Peninsula. Our results
showed that the populations of A. hispanica are strongly differentiated (high and
significant FST and FST values, corroborated by the results from AMOVA and
SAMOVA) and genetically diversified. We suggest that the restricted gene flow
between populations may have been potentiated by ecological, hydrological and
anthropogenic causes. Bayesian skyline plots revealed a signal for expansion for
all populations (tMRCA between 68kya and 1.33Mya) and a genetic diversity
latitudinal gradient was detected between the populations from the Upper (more
diversified) and the Lower (less diversified) Guadiana river basin. We postulate
a Pleistocenic westwards colonization route for A. hispanica in the Guadiana
river basin, which is in agreement with the tempo and mode of paleoevolution of
this drainage. The colonization of River Guadalquivir around 60kya with migrants
from the Upper Guadiana, most likely by stream capture, is also suggested. This
study highlights the view that critically endangered species facing range
retreats (about 47% of its known populations have disappeared in the last
15years) are not necessarily small and genetically depleted. However, the
extinction risk is not negligible since A. hispanica faces the combined effect of
several deterministic and stochastic negative factors and, moreover,
recolonization events after localized extinctions are very unlikely to occur due
to the strong isolation of populations and to the patchily ecologically
conditioned distribution of fish. The inferred species distribution models
highlight the significant contribution of temperature seasonality and
isothermality to A. hispanica occurrence in Guadiana environments and emphasize
the importance of stable climatic conditions for the preservation of this
species. Given the strong population structure, high percentage of private
haplotypes and virtual absence of inter-basin gene flow we suggest that each A.
hispanica population should be considered as an independent Operational
Conservation Unit and that ex-situ and in-situ actions should be conducted in
parallel to allow for the long-term survival of the species and the preservation
of the genetic integrity of its populations.
PMID- 25132128
TI - Mitochondrial genomes reveal the pattern and timing of marten (Martes), wolverine
(Gulo), and fisher (Pekania) diversification.
AB - Despite recent advances in understanding the pattern and timescale of
evolutionary diversification in the marten, wolverine, fisher, and tayra
subfamily Guloninae (Mustelidae, Carnivora), several important issues still
remain contentious. Among these are the phylogenetic position of Gulo relative to
the subgenera of Martes (Martes and Charronia), the phylogenetic relationships
within the subgenus Martes, and the timing of gulonine divergences. To elucidate
these issues we explored nucleotide variation in 11 whole mitochondrial genomes
(mitogenomes) from eight gulonine species and two outgroup meline species.
Parsimony, maximum likelihood, and Bayesian phylogenetic analyses yielded fully
resolved and identical patterns of relationships with high support for all
divergences. The generic status of Pekania (P. pennanti), the monophyly of the
genus Martes containing M. flavigula (subgenus Charronia) to the exclusion of the
genus Gulo (G. gulo), and the M. foina (M. americana (M. melampus (M. zibellina,
M. martes))) phylogeny of the subgenus Martes were strongly supported. Dating
analyses (BEAST) using a set of five newly applied fossil calibrations provided
divergence times considerably younger than previous multigene mitochondrial
estimates, but similar to multigene nuclear and nuclear-mitochondrial estimates.
The 95% confidence (highest posterior density) intervals of our divergence times
fell within those inferred from nuclear and nuclear-mitochondrial sequence data,
and were markedly narrower than in earlier studies (whether nuclear,
mitochondrial, or combined). Notably, and contrary to long-held beliefs, our
findings indicate that fossils older than the Tortonian-Messinian transition
(late Late Miocene) do not represent Martes, excluding from this genus its
putative members from the Early, Middle, and early Late Miocene. This study
demonstrates the high informativeness of the mitogenome for phylogenetic
inference and divergence time estimation within Guloninae, and suggests that
mitogenomes can be highly informative also for other clades at similar levels of
evolutionary divergence.
PMID- 25132129
TI - When everything converges: integrative taxonomy with shell, DNA and venomic data
reveals Conus conco, a new species of cone snails (Gastropoda: Conoidea).
AB - Cone snails have long been studied both by taxonomists for the diversity of their
shells and by biochemists for the potential therapeutic applications of their
toxins. Phylogenetic approaches have revealed that different lineages of Conus
evolved divergent venoms, a property that is exploited to enhance the discovery
of new conotoxins, but is rarely used in taxonomy. Specimens belonging to the
Indo-West Pacific Conus lividus species complex were analyzed using phenetic and
phylogenetic methods based on shell morphology, COI and 28S rRNA gene sequences
and venom mRNA expression and protein composition. All methods converged to
reveal a new species, C. conco n. sp. (described in Supplementary data),
restricted to the Marquesas Islands, where it diverged recently (~3mya) from C.
lividus. The geographical distribution of C. conco and C. lividus and their
phylogenetic relationships suggest that the two species diverged in allopatry.
Furthermore, the diversity of the transcript sequences and toxin molecular masses
suggest that C. conco evolved unique toxins, presumably in response to new
selective pressure, such as the availability of new preys and ecological niches.
Furthermore, this new species evolved new transcripts giving rise to original
toxin structures, probably each carrying specific biological activity.
PMID- 25132130
TI - What do we really fear? The epidemiological characteristics of Ebola and our
preparedness.
AB - Ebola virus disease (hereafter Ebola) has a high fatality rate; currently lacks a
treatment or vaccine with proven safety and efficacy, and thus many people fear
this infection. As of August 13, 2014, 2,127 patients across four West African
countries have been infected with the Ebola virus over the past nine months.
Among these patients, approximately 1 in 2 has subsequently died from the
disease. In response, the World Health Organization has declared the Ebola
outbreak in West Africa to be a Public Health Emergency of International Concern.
However, Ebola is only transmitted by patients who already present symptoms of
the disease, and infection only occurs upon direct contact with the blood or body
fluids of an Ebola patient. Consequently, transmission of the outbreak can be
contained through careful monitoring for fever among persons who have visited, or
come into contact with persons from, the site of the outbreak. Thus, patients
suspected of presenting symptoms characteristic of Ebola should be quarantined.
To date, South Korea is not equipped with the special containment clinical units
and biosafety level 4 facilities required to contain the outbreak of a fatal
virus disease, such as Ebola. Therefore, it is necessary for South Korea to make
strategies to the outbreak by using present facilities as quickly as possible. It
is also imperative that the government establish suitable communication with its
citizens to prevent the spread of uninformed fear and anxiety regarding the Ebola
outbreak.
PMID- 25132131
TI - The transcription factor VvWRKY33 is involved in the regulation of grapevine
(Vitis vinifera) defense against the oomycete pathogen Plasmopara viticola.
AB - Grapevine (Vitis vinifera ssp. vinifera) is one of the most important fruit
species; however, it is highly susceptible to various pathogens, which can cause
severe crop losses in viticulture. It has been shown that several WRKY class
transcription factors (TFs) are part of the signal transduction cascade, which
leads to the activation of plant defense reactions against various pathogens. In
the present investigation, a full-length cDNA was isolated from V. vinifera leaf
tissue encoding a predicted protein, designated VvWRKY33, which shows the
characteristics of group I WRKY protein family. VvWRKY33 induction correlates
with the expression of VvPR10.1 (pathogenesis-related 10.1) gene in the leaves of
the resistant cultivar 'Regent' after infection with Plasmopara viticola, whereas
in the susceptible cultivar 'Lemberger' VvWRKY33 and VvPR10.1 are not induced.
Corresponding expression of the TF and VvPR10.1 was even obtained in uninfected
ripening berries. In planta, analysis of VvWRKY33 has been performed by ectopic
expression of VvWRKY33 in grapevine leaves of greenhouse plants mediated via
Agrobacterium tumefaciens transformation. In consequence, VvWRKY33 strongly
increases resistance to P. viticola in the susceptible cultivar 'Shiraz' and
reduces pathogen sporulation of about 50-70%, indicating a functional role for
resistance in grapevine. Complementation of the resistance-deficient Arabidopsis
thaliana Columbia-0 (Col-0) mutant line wrky33-1 by constitutive expression of
VvWRKY33 restores resistance against Botrytis cinerea to wild-type level and in
some complemented mutant lines even exceeds the resistance level of the parental
line Col-0. Our results support the involvement of VvWRKY33 in the defense
reaction of grapevine against different pathogens.
PMID- 25132132
TI - Malignant effects of multiple rare variants in sarcomere genes on the prognosis
of patients with hypertrophic cardiomyopathy.
AB - AIMS: Although genetic testing has been recommended in patients with hypertrophic
cardiomyopathy (HCM) in current clinical practice, its utility in prognostic
prediction remains to be ascertained. We assessed the dosage effect of rare
variants in sarcomere genes on the long-term outcomes of HCM. METHODS AND
RESULTS: A total of 529 unrelated HCM patients were prospectively recruited and
followed for 4.7 +/- 3.2 years. Eight sarcomere genes were screened with targeted
resequencing and identified variants were validated through Sanger sequencing.
After polymorphisms and likely neutral rare variants were excluded, the patients
were segregated into three groups based on the dosage of rare variants: no rare
variant, a single rare variant, and multiple rare variants. Multiple rare
variants were identified in 7.2% (38/529) of the study patients. Patients with
multiple rare variants were younger at diagnosis, and had greater maximum LV wall
thicknesses and larger left atria. The risk for cardiovascular death in patients
with multiple rare variants was higher than in those without rare variants (P =10
5) or in those with a single rare variant (P = 2 * 10-5). Multivariable analysis
revealed that multiple rare variants were a risk factor for cardiovascular death
[hazard ratio (HR) 3.74, 95% confidence interval (CI) 1.84-7.58, P = 0.0003], as
well as sudden cardiac death (HR 3.57, 95% CI 1.23-10.35, P = 0.019) and heart
failure-related death (HR 4.62, 95% CI 1.67-12.76, P = 0.003). CONCLUSIONS: The
presence of multiple rare variants in sarcomere genes is a risk factor for
malignant outcomes in HCM, and may be appropriate to consider as a criterion in
the risk stratification of HCM patients.
PMID- 25132133
TI - Recent advances in germination of Clostridium spores.
AB - Members of Clostridium genus are a diverse group of anaerobic spore-formers that
includes several pathogenic species. Their anaerobic requirement enhances the
importance of the dormant spore morphotype during infection, persistence and
transmission. Bacterial spores are metabolically inactive and may survive for
long times in the environment and germinate in presence of nutrients termed
germinants. Recent progress with spores of several Clostridium species has
identified the germinant receptors (GRs) involved in nutrient germinant
recognition and initiation of spore germination. Signal transduction from GRs to
the downstream effectors remains poorly understood but involves the release of
dipicolinic acid. Two mechanistically different cortex hydrolytic machineries are
present in Clostridium spores. Recent studies have also shed light into novel
biological events that occur during spore formation (accumulation of
transcriptional units) and transcription during early spore outgrowth. In
summary, this review will cover all of the recent advances in Clostridium spore
germination.
PMID- 25132135
TI - Moderating effects of nurses' organizational justice between organizational
support and organizational citizenship behaviors for evidence-based practice.
AB - BACKGROUND: Lack of existing literature on the correlation among organizational
justice, organizational support, and organizational citizenship behaviors has
created a research gap in previous evidence-based practice (EBP) studies on
nursing personnel. AIMS: To investigate whether organizational justice among
nurses has a moderating effect between their organizational support and
organizational citizenship behaviors in order to bridge such a gap of existing
literature with the EBP study on nursing personnel. METHODS: Nursing staff of one
large and influential hospital in Taiwan was surveyed. Four hundred
questionnaires were distributed, and 386 were collected with a valid response
rate of 96.50%. SPSS 17.0 and Amos 17.0 statistical software packages were used
for data analysis. RESULTS: Nurses' organizational support positively influences
their organizational citizenship behaviors, and their organizational justice
perception has a positive moderating effect between organizational support and
organizational citizenship behaviors. LINKING EVIDENCE TO ACTION: Results call
hospitals' attention to the type of individual behaviors that may improve
organizational performance. When nursing staff perceive fair and impartial
treatment by the organization and supportive emotional attachment, behaviors
beneficial for the organization are expressed in return. Subjective perceptions
of nursing staff play an important role in organizational exchange relationship;
the higher the degree of nursing staff's perceived organizational justice, the
higher the degree of their organizational support, perception, and exhibition of
organizational citizenship behaviors such as altruistic behavior and dedication
to the work.
PMID- 25132136
TI - Life history responses of Daphnia similoides simultaneously exposed to
microcystin-LR and ammonia and their postexposure recovery.
AB - Aquatic organisms often suffer episodic stress from cyanobacterial bloom-derived
concomitants and sometimes interactive stressors, and they may recover when
stressors terminate. To assess whether exposed Daphnia can quickly recover from
combined toxicity of bloom-derived stressors, Daphnia similoides were exposed to
mixtures of ammonia (0 mg L(-1) , 0.37 mg L(-1) , and 0.58 mg L(-1) ) and
dissolved microcystin-LR (0 ug L(-1) , 10 ug L(-1) , 30 ug L(-1) , and 100 ug L(
1) ) in a full factorial design for 14 d and subsequently allowed to recover for
7 d. During the exposure, the mixtures of ammonia and microcystin-LR showed
different effects on the selected variables. Ammonia delayed the time to
maturation, but microcystin-LR was not negative to the development of the tested
daphnids. Furthermore, microcystin-LR reduced the prolonged developmental time to
first eggs and first clutch caused by high ammonia. The total reproduction of D.
similoides was dramatically reduced by 64% to 79% by both toxicants and their
combinations, but there were no interactive effects. After the recovery period,
organisms under most treatments did not recover completely from the combined
stress but showed positive signs of recovery, based on the size of the last
clutch and the mean number of clutches during recovery; thus the affected D.
similoides have the potential to quickly recover from the combined toxic
stressors.
PMID- 25132137
TI - Uncovering a broad class of fluorescent amine-containing compounds by heat
treatment.
AB - Amine-containing compounds including polymers, oligomers and small molecules,
without conventional fluorophores, are found to emit strong visible fluorescence
after a one-step heat treatment. Furthermore, our results demonstrate for the
first time that not only tertiary amine groups but also primary and secondary
amine groups can act as fluorescent moieties.
PMID- 25132134
TI - Calcium affects OX1 orexin (hypocretin) receptor responses by modifying both
orexin binding and the signal transduction machinery.
AB - BACKGROUND AND PURPOSE: One of the major responses upon orexin receptor
activation is Ca(2+) influx, and this influx seems to amplify the other responses
mediated by orexin receptors. However, the reduction in Ca(2+) , often used to
assess the importance of Ca(2+) influx, might affect other properties, like
ligand-receptor interactions, as suggested for some GPCR systems. Hence, we
investigated the role of the ligand-receptor interaction and Ca(2+) signal
cascades in the apparent Ca(2+) requirement of orexin-A signalling. EXPERIMENTAL
APPROACH: Receptor binding was assessed in CHO cells expressing human OX1
receptors with [(125) I]-orexin-A by conventional ligand binding as well as
scintillation proximity assays. PLC activity was determined by chromatography.
KEY RESULTS: Both orexin receptor binding and PLC activation were strongly
dependent on the extracellular Ca(2+) concentration. The relationship between
Ca(2+) concentration and receptor binding was the same as that for PLC
activation. However, when Ca(2+) entry was reduced by depolarizing the cells or
by inhibiting the receptor-operated Ca(2+) channels, orexin-A-stimulated PLC
activity was much more strongly inhibited than orexin-A binding. CONCLUSIONS AND
IMPLICATIONS: Ca(2+) plays a dual role in orexin signalling by being a
prerequisite for both ligand-receptor interaction and amplifying orexin signals
via Ca(2+) influx. Some previous results obtained utilizing Ca(2+) chelators have
to be re-evaluated based on the results of the current study. From a drug
discovery perspective, further experiments need to identify the target for Ca(2+)
in orexin-A-OX1 receptor interaction and its mechanism of action.
PMID- 25132138
TI - The prevalence of type 1 diabetes mellitus among 15-34-year-aged Lithuanian
inhabitants during 1991-2010.
AB - AIMS: To summarize the data on the prevalence of type 1 diabetes mellitus among
15-34-year-aged Lithuania inhabitants (1991-2010). METHODS: New prevalent cases
consist of growing-up patients with diabetes onset in childhood, i.e., up to 14
years, new onset 15-34-year-aged type 1 diabetic patients Lithuanian inhabitants,
and immigrants. The data on type 1 diabetes was collected with the help of
general practitioners and regional endocrinologists in Lithuania. RESULTS: On 31
December 1991, there were 1202 adolescent and adult 15-34-year-aged patients with
type 1 diabetes mellitus or 103.59 per 100,000 inhabitants of the same age group
(95% Poisson CI 97.90-109.62), and at the end of 2010 - 1533 or 187.80 (178.63
197.44), respectively in Lithuania. During 19-year period the mean increase of
type 1 diabetic patients was 1.25+/-1.94% per year or 1.47+/-2.74 per 100,000
inhabitants per mean year of the study period (for males 1.42+/-2.14% or 1.69+/
3.05/100,000 and for females 1.05+/-1.99%, or 1.24+/-2.92/100,000). Regression
based linear trends showed that the prevalence of type 1 diabetes mellitus in 15
34-year-age group had a tendency to increase among males (r=0.953; p<0.001) and
females (r=0.970; p<0.001). The age adjusted prevalence frequencies for males and
females in 1991 were correspondingly 102.81/100,000 and 104.55/100,000, and in
2010 - 193.75 and 182.01. CONCLUSION: The prevalence of type 1 diabetes mellitus
among 15-34-year-age males and females had a tendency to increase during 1991
2010.
PMID- 25132139
TI - Metabolic control and therapeutic profile of patients with diabetes in Portuguese
primary care (TEDDI CP).
AB - AIM: To evaluate the metabolic control rate and to characterize the therapeutic
profile of patients with Type 2 diabetes mellitus (DM2) from Portuguese primary
care of National Health Service. METHODS: Cross-sectional multicentre study
conducted in Portuguese primary health care units between July 2011 and May 2012.
A national representative sample of 1528 DM2 patients was selected from 51 units,
stratified by region. Socio-demographic, anthropometric, lifestyle,
cardiometabolic risk factors, disease status, HbA1c levels and therapeutic
information were collected. RESULTS: Patients' mean age was 65+/-10.7 years
(50.4% males) and median duration of disease was 7 years: range (0-45 years).
Almost 8% were smokers, 80.3% had hypertension, 61.6% hypercholesterolemia and
almost 15% cardiovascular disease. Patients' health condition was classified with
a score of 4 or 5 (excellent) for 60.6%. Median HbA1c was 6.6% (min-max: 4.2%
13.4%), 64.8% of the patients had HbA1c<7.0% and 49.2% HbA1c<=6.5%. Oral
antidiabetics were used in 94.4% of the patients, antihypertensives in 80.6%,
antidyslipidemics in 72.0%, antiplatelet agents in 50.6% and insulin in 8.3%.
CONCLUSIONS: Metabolic control rate was good according to current guidelines.
However, patients with higher HbA1c levels had longer time since diagnosis, worse
current health condition, hypertriglyceridemia and were insulin-treated.
PMID- 25132140
TI - Evaluation of knowledge regarding gestational diabetes mellitus and its
association with glycaemic level: A Malaysian study.
AB - AIMS: The aim of this study was to evaluate the knowledge about GDM and its
corresponding relation with glycaemic level in GDM patients. METHOD: A cross
sectional study was conducted in antenatal clinic of Hospital Pulau Pinang,
Malaysia from June 2013 to December 2013 using Gestational Diabetes Mellitus
Knowledge Questionnaire (GDMKQ) on the sample of 175 GDM patients. Three most
recent fasting plasma glucose (FPG) values (mmol/l) were taken from patients
profiles and mean was calculated. RESULTS: A total of 166 patients were included
in final analysis. A total mean knowledge score of 166 patients was 10.01+/-3.63
and total mean FPG value was 5.50+/-1.13. Knowledge had a significant negative
association with FPG (r=- 0.306, P<0.01). Among different knowledge domains,
highest mean score was seen for diet/food values domain and lowest for management
of GDM. Educational level seems to be the most significant predictor of GDM
knowledge and glycaemic control. Highest mean knowledge score and lowest mean
glycaemic levels were recorded for patients aged 25-29 years, Malay ethnicity,
working women and family history of DM. CONCLUSION: Higher Knowledge about GDM is
related to better glycaemic control. New educational strategies should be
developed to improve the lower health literacy.
PMID- 25132141
TI - Morphological and proteomic characterization of midgut of the malaria vector
Anopheles albimanus at early time after a blood feeding.
AB - The midgut of anopheline mosquito is the entry of Plasmodium, the causative agent
of malaria.When the mosquito feeds on parasite infected host, Plasmodium
parasites reach the midgut and must confront digestive enzymes, the innate immune
response and go across the peritrophic matrix (PM), a thick extracellular sheath
secreted by the mosquito midgut epithelial cells. Then, to continue its
development, the parasite must reach the salivary glands to achieve transmission
to a vertebrate host. We report here the morphological and biochemical
descriptions of the midgut changes after a blood meal in Anopheles albimanus.
Before blood feeding, midgut epithelial cells contained numerous electrondense
vesicles distributed in the central to apical side. These vesicles were secreted
to the luminal side of the midgut after a blood meal. At early times after blood
ingest, the PM is formed near microvilli as a granulous amorphous material and
after it consolidates forming a highly organized fibrillar structure, constituted
by layers of electrondense and electronlucent regions. Proteomic comparative
analysis of sugar and blood fed midguts showed several molecules that modify
their abundance after blood intake; these include innate immunity, cytoskeletal,
stress response, signaling, and digestive, detoxifying and metabolism enzymes.
Biological significance In the midgut of mosquitoes during bloodfeeding, many
simultaneous processes occur, including digestion, innate immune activities,
cytoskeleton modifications, construction of a peritrophic matrix and hormone
production, between others. Mechanical forces are very intense during
bloodfeeding and epithelial and muscular cells must resist the stress, modifying
the actin cytoskeleton and coordinating intracellular responses by signaling.
Microorganisms present in midgut contents reproduce and interact with epithelial
cells triggering innate immune response. When infectious agents are present in
the blood meal they must traverse the peritrophic matrix, an envelope formed from
secretion products of epithelial cells, and evade the immune system in order to
reach the epithelium and continue their journey towards salivary glands, in
preparation for the transmission to the new hosts. During all these processes,
proteins of mosquitoes are modified in order to deal with mechanical and
biological challenges, and the aim of this work is to study these changes.
PMID- 25132142
TI - Data worth and prediction uncertainty for pesticide transport and fate models in
Nebraska and Maryland, United States.
AB - BACKGROUND: Complex environmental models are frequently extrapolated to overcome
data limitations in space and time, but quantifying data worth to such models is
rarely attempted. The authors determined which field observations most informed
the parameters of agricultural system models applied to field sites in Nebraska
(NE) and Maryland (MD), and identified parameters and observations that most
influenced prediction uncertainty. RESULTS: The standard error of regression of
the calibrated models was about the same at both NE (0.59) and MD (0.58), and
overall reductions in prediction uncertainties of metolachlor and metolachlor
ethane sulfonic acid concentrations were 98.0 and 98.6% respectively. Observation
data groups reduced the prediction uncertainty by 55-90% at NE and by 28-96% at
MD. Soil hydraulic parameters were well informed by the observed data at both
sites, but pesticide and macropore properties had comparatively larger
contributions after model calibration. CONCLUSIONS: Although the observed data
were sparse, they substantially reduced prediction uncertainty in unsampled
regions of pesticide breakthrough curves. Nitrate evidently functioned as a
surrogate for soil hydraulic data in well-drained loam soils conducive to
conservative transport of nitrogen. Pesticide properties and macropore parameters
could most benefit from improved characterization further to reduce model misfit
and prediction uncertainty.
PMID- 25132143
TI - Efficacy of combination therapy of oral zinc sulfate with imiquimod, podophyllin
or cryotherapy in the treatment of vulvar warts.
AB - AIM: Zinc sulfate is beneficial in the treatment of epithelial warts. We
conducted this study to compare the efficacy of combination therapy of oral zinc
sulfate with conventional treatments in the treatment of vulvar warts. MATERIAL
AND METHODS: This study was a randomized controlled trial. The sample size was 42
in each group. Women aged 20-50 years were placed by the block randomized method
into six groups: the podophyllin-, imiquimod- and cryotherapy-treated groups, and
another three groups receiving 8-week combination therapy of 400 mg oral zinc
sulfate with one of the above-mentioned treatments. Data were analyzed using
anova and Fischer's exact test with spss16. RESULTS: A total of 228 patients were
recruited and completed the study in six treatment groups. No significant
difference was observed in the response to treatment among these groups. Relapse
after 6 months was significantly higher in the podophyllin-, imiquimod- and
cryotherapy-treated patients compared to patients receiving these treatments in
combination with oral zinc sulfate (P<0.05). CONCLUSIONS: Combined therapy of
oral zinc sulfate with conventional treatments of vulvar warts appears to reduce
the relapse rate.
PMID- 25132144
TI - Treatment with Evasin-3 abrogates neutrophil-mediated inflammation in mouse acute
pancreatitis.
AB - BACKGROUND: Acute pancreatitis is characterized by inflammatory processes
affecting not only the pancreas, but also the lung. Here, we investigated timing
of leucocyte infiltration and chemokine expression within lung and pancreas
during pancreatitis and whether treatments selectively inhibiting chemokines
(using Evasins) could improve organ injury. MATERIAL AND METHODS: C57Bl/6 mice
were submitted in vivo to 10-h intraperitoneal injections of cerulein and
followed for up to 168 h. Five minutes after the first cerulein injection, a
single intraperitoneal injection of 10 MUg Evasin-3, 1 MUg Evasin-4 or an equal
volume of vehicle (PBS) was performed. Leucocytes, reactive oxygen species (ROS),
necrosis and chemokine/cytokine mRNA expression were assessed in different organs
by immunohistology and real-time RT-PCR, respectively. RESULTS: In the lung,
neutrophil infiltration and macrophage infiltration peaked at 12 h and were
accompanied by increased CXCL2 mRNA expression. CCL2, CXCL1 and TNF-alpha
significantly increased after 24 h as compared to baseline. No increase in CCL3
and CCL5 was observed. In the pancreas, neutrophil infiltration peaked at 6 h,
while macrophages increased only after 72 h. Treatment with Evasin-3 decreased
neutrophil infiltration, ROS production and apoptosis in the lung and reduced
neutrophils, macrophages apoptosis and necrosis in the pancreas. Evasin-4 only
reduced macrophage content in the lung and did not provide any benefit at the
pancreas level. CONCLUSION: Chemokine production and leucocyte infiltration are
timely regulated in lung and pancreas during pancreatitis. CXC chemokine
inhibition with Evasin-3 improved neutrophil inflammation and injury, potentially
interfering with damages in acute pancreatitis and related pulmonary
complications.
PMID- 25132145
TI - Quantitative volatile compound profiles in fungal cultures of three different
Fusarium graminearum chemotypes.
AB - Biosynthesis in fungal cultures of 27 Fusarium graminearum isolates of three
different chemotypes (3AcDON, 15AcDON and NIV) grown on yeast extract sucrose
agar medium was examined in this study. Volatile organic compound (VOC) analysis
performed by headspace solid phase microextraction GC-MS allowed for
determination of various concentrations of six alcohols, 14 aldehydes and
ketones, 10 benzene derivatives, one furane, five hydrocarbons and three
terpenes. In general, the determined VOC profile in fungal cultures was dominated
by hexanal (up to 74%), followed by nonanal (18%) and 2-methylbutanal (18%).
Principal component analysis and discriminant analysis based on VOCs allowed for
unambiguous discrimination of all studied isolates into three different groups in
accordance with their trichothecene production (chemotypes). Significant
differences were revealed between the levels of aldehydes and ketones, benzene
derivatives and hydrocarbons in fungal cultures of three F. graminearum
chemotypes.
PMID- 25132146
TI - Development and usability of a computer-tailored pedometer-based physical
activity advice for breast cancer survivors.
AB - This observational study aimed to adapt a computer-tailored step advice for the
general population into a feasible advice for breast cancer survivors and to test
its usability. First, several adaptations were made to the original design
(adding cancer-related physical activity (PA) barriers and beliefs, and self
management strategies to improve survivors' personal control). Second, the
adapted advice was evaluated in two phases: (1) a usability testing in healthy
women (n = 3) and survivors (n = 6); and (2) a process evaluation during 3 weeks
in breast cancer survivors (n = 8). Preliminary usability testing revealed no
problems during logging-in; however, three survivors misinterpreted some
questions. After refining the questionnaire and advice, survivors evaluated the
advice as interesting, attractive to read, comprehensible and credible. Inactive
survivors found the advice novel, but too long. The process evaluation indicated
that the majority of the women (n = 5/8) reported increased steps. Monitoring
step counts by using a pedometer was perceived as an important motivator to be
more active. To conclude, this study provides initial support for the usability
and acceptability of a computer-tailored pedometer-based PA advice for breast
cancer survivors. After testing efficacy and effectiveness of this intervention,
this tool can broaden the reach of PA promotion in breast cancer survivors.
PMID- 25132147
TI - Serum hepatitis B virus RNA levels as an early predictor of hepatitis B envelope
antigen seroconversion during treatment with polymerase inhibitors.
AB - Hepatitis B envelope antigen (HBeAg) seroconversion represents an endpoint of
treatment of chronic hepatitis B virus (HBV) infections. We have studied whether
levels of serum HBV RNA during polymerase inhibitor treatment might be helpful
for predicting HBeAg seroconversion. HBV RNA levels were determined in serial
serum samples from 62 patients with chronic HBV infection (50 HBeAg positive).
Patients received antiviral treatment for a mean duration of 30 +/- 15 (range, 4
64) months. A new rapid amplification of complimentary DNA-ends-based real-time
polymerase chain reaction was established for quantitative analysis of
polyadenylated full-length (fl) and truncated (tr) HBV RNA. HBV RNA, HBV DNA, and
hepatitis B surface antigen (HBsAg) levels as well as presence of HBeAg and
hepatitis B envelope antibody were measured at baseline, month 3, month 6, and
subsequent time points. Fifteen patients who achieved HBeAg seroconversion after
a mean duration of 19 +/- 14 (range, 3-56) months of antiviral treatment showed a
significantly stronger decline in mean HBV flRNA and trRNA levels from baseline
to month 3 of 1.0 +/- 1.4 (range, -1.6-3.4) and 2.1 +/- 1.4 (range, 0-3.9) and to
month 6 of 1.8 +/- 1.4 (range, 0-4.6) and 3.1 +/- 1.7 (range, 0-5.1) log10
copies/mL, respectively, in comparison to 35 HBeAg-positive patients without
HBeAg seroconversion (P < 0.001 for months 3 and 6). A similar decline in HBV RNA
levels was observed in HBeAg-negative patients. The decline of HBV RNA levels at
months 3 and 6 of treatment was to be the strongest predictor of HBeAg
seroconversion, when compared to levels of HBV DNA, HBsAg, alanine
aminotransferase, and HBV genotype, age, and sex. CONCLUSION: Serum HBV RNA
levels may serve as a novel tool for prediction of serological response during
polymerase inhibitor treatment in HBeAg-positive patients.
PMID- 25132148
TI - Predictors of early poor aesthetic outcome after breast-conserving surgery in
patients with breast cancer: initial results of a prospective cohort study at a
single institution.
AB - BACKGROUND AND OBJECTIVES: The aim of this study was to explore features of
patients reporting early poor aesthetic outcome after simple breast-conserving
surgery. METHODS: We prospectively evaluated 709 patients shortly after breast
conserving surgery. Aesthetic outcome was measured by aesthetic status scores of
the Breast Cancer Treatment Outcome Scale. Clinical, surgical, and pathologic
variables were assessed to identify predictors of poor aesthetic outcome.
RESULTS: Poor aesthetic outcome was reported by 46 (6.5%) patients, and 209 (29%)
patients reported an intermediate aesthetic outcome. A single factor analysis of
variance showed a negative impact of higher specimen weight (P < 0.001).
Univariate logistic regression analysis revealed the following significant risk
factors for poor aesthetic outcome: 12 o'clock positioning of tumor localization,
a tumor behind the nipple areolar complex (NAC), fishmouth-shaped incision with
resection of the NAC, quadrantectomy, central segmental resection, and pT stages
3 and 4. Multivariate logistic regression analysis indicated statistically
independent associations between poor aesthetic outcome and tumor position in the
inner half of the breast or behind the NAC, quadrantectomy, and pT stages 3 and
4. CONCLUSION: Poor aesthetic outcome is relatively rare shortly after breast
conserving surgery, but predictable in specific situations.
PMID- 25132149
TI - The importance of parental knowledge: evidence from weight report cards in
Mexico.
AB - The rise of childhood obesity in less developed countries is often overlooked. We
study the impact of body weight report cards in Mexico. The report cards
increased parental knowledge and shifted parental attitudes about children's
weight. We observe no meaningful changes in parental behaviors or children's body
mass index. Interestingly, parents of children in the most obese classrooms were
less likely to report that their obese child weighed too much relative to those
in the least obese classrooms. As obesity rates increase, reference points for
appropriate body weights may rise, making it more difficult to lower obesity
rates.
PMID- 25132150
TI - The kinematic relationship between sitting and standing posture and pelvic
inclination and its significance to cup positioning in total hip arthroplasty.
AB - PURPOSE: The aim of this study is to describe the influence of sitting and
standing posture on sagittal pelvic inclination in total hip replacement patients
to assist with correct acetabular component positioning. METHODS: Lateral
radiographs of the pelvis and lumbar spine in sitting and standing positions were
extracted. Pelvic tilt was measured using the vertical inclination of a line from
the anterior superior iliac spine (ASIS) to pubic tubercle. Sacral inclination,
Cobb angle of the lumbar spine and hip flexion were recorded. RESULTS: Sixty
patients were identified with a mean age of 63. Men were more likely to flex the
lumbar spine in sitting (p = 0.004); 80 degrees of hip flexion is required for
seated posture. Stiff hips required compensatory pelvic flexion and lumbar
flexion in sitting. There is a linear relationship between hip flexion and pelvic
tilt, hip flexion and lumbar lordosis. CONCLUSIONS: Pelvic orientation is
determined by lumbar and hip stiffness. This impacts on acetabular version.
PMID- 25132151
TI - Brain derived neurotrophic factor gene (BDNF) and personality traits: the
modifying effect of season of birth and sex.
AB - Personality traits are complex phenotypes influenced by interactions of multiple
genetic variants of small effect and environmental factors. It has been suggested
that the brain derived neurotrophic factor gene (BDNF) is involved in personality
traits. Season of birth (SOB) has also been shown to affect personality traits
due to its influences on brain development during prenatal and early postnatal
periods. The present study aimed to investigate the effects of BDNF on
personality traits; and the modifying effects of SOB and sex on associations
between BDNF and personality traits. A sample of 1018 young adults (68% women;
age range 17-25years) of Caucasian origin from the Russian Federation was
assessed on personality traits (Novelty Seeking, Harm Avoidance, Reward
Dependence, Persistence, Self-directedness, Cooperativeness, Self-transcendence)
with the Temperament and Character Inventory-125 (TCI-125). Associations between
personality traits and 12 BDNF SNPs were tested using linear regression models.
The present study demonstrated the effect of rs11030102 on Persistence in females
only (PFDR=0.043; r(2)=1.3%). There were significant interaction effects between
Val66Met (rs6265) and SOB (PFDR=0.048, r(2)=1.4%), and between rs2030323 and SOB
(PFDR=0.042, r(2)=1.3%), on Harm Avoidance. Our findings provide evidence for the
modifying effect of SOB on the association between BDNF and Harm Avoidance, and
for the modifying effect of sex on the association between BDNF and Persistence.
PMID- 25132152
TI - microRNAs: role in leukemia and their computational perspective.
AB - MicroRNAs (miRNAs) belong to the family of noncoding RNAs (ncRNAs) and had gained
importance due to its role in complex biochemical pathways. Changes in the
expression of protein coding genes are the major cause of leukemia. Role of
miRNAs as tumor suppressors has provided a new insight in the field of leukemia
research. Particularly, the miRNAs mediated gene regulation involves the
modulation of multiple mRNAs and cooperative action of different miRNAs to
regulate a particular gene expression. This highly complex array of regulatory
pathway network indicates the great possibility in analyzing and identifying
novel findings. Owing to the conventional, slow experimental identification
process of miRNAs and their targets, the last decade has witnessed the
development of a large amount of computational approaches to deal with the
complex interrelations present within biological systems. This article describes
the various roles played by miRNAs in regulating leukemia and the role of
computational approaches in exploring new possibilities.
PMID- 25132153
TI - A note on the efficiencies of sampling strategies in two-stage Bayesian regional
fine mapping of a quantitative trait.
AB - In focused studies designed to follow up associations detected in a genome-wide
association study (GWAS), investigators can proceed to fine-map a genomic region
by targeted sequencing or dense genotyping of all variants in the region, aiming
to identify a functional sequence variant. For the analysis of a quantitative
trait, we consider a Bayesian approach to fine-mapping study design that
incorporates stratification according to a promising GWAS tag SNP in the same
region. Improved cost-efficiency can be achieved when the fine-mapping phase
incorporates a two-stage design, with identification of a smaller set of more
promising variants in a subsample taken in stage 1, followed by their evaluation
in an independent stage 2 subsample. To avoid the potential negative impact of
genetic model misspecification on inference we incorporate genetic model
selection based on posterior probabilities for each competing model. Our
simulation study shows that, compared to simple random sampling that ignores
genetic information from GWAS, tag-SNP-based stratified sample allocation methods
reduce the number of variants continuing to stage 2 and are more likely to
promote the functional sequence variant into confirmation studies.
PMID- 25132154
TI - PCR-based prediction of type I beta-exotoxin production in Bacillus thuringiensis
strains.
AB - Some Bacillus thuringiensis strains secrete type I beta-exotoxin, which is a non
specific insecticidal and thermostable adenine nucleoside oligosaccharide.
Toxicity bioassays and HPLC are traditional methods for detecting beta-exotoxin.
With the aim of establish a first rapid approach for prediction of type I beta
exotoxin production, two PCR-based methods were successfully evaluated in B.
thuringiensis strains and native isolates. In order to validate a reliable
technology, results obtained by this method were correlated with that obtained
from Musca domestica bioassays.
PMID- 25132155
TI - Metabolite profile deviations in an oral glucose tolerance test-a comparison
between lean and obese individuals.
AB - OBJECTIVE: While impaired glucose tolerance diagnosed by the oral glucose
tolerance test (OGTT) is a common trait in obese individuals, less is known about
changes in levels of other metabolites. The aim was to reveal the complex
alterations in metabolite levels provoked by an OGTT and its perturbation in
obese individuals. METHODS: Gas chromatography/mass spectrometry was used to
profile metabolite levels in serum from 14 obese participants (body mass index
[BMI] of 43.6 +/- 1.5 kg m(-2) [mean +/- SEM]) at 0, 30, and 120 min during a
standard 2-h 75 g OGTT. Metabolite profiles from six lean individuals (BMI of
22.4 +/- 2.4 kg m(-2) ), collected from a previous study, were included for
comparison. RESULTS: In the obese group, 59 metabolite profiles were determined.
Among these, 16 deviated from profiles in the lean group. Deviating metabolites
were categorized into three groups. Delayed reduction in levels of five fatty
acids. Increased levels at 30 min of five amino acids, including isoleucine and
leucine. A blunted increase at 30 min of six metabolites. CONCLUSIONS:
Metabolomics analysis revealed distinct differences in alterations of metabolite
levels during an OGTT in obese and lean subjects. To this end, our data suggests
a disrupted regulation of ketogenesis, lipolysis and proteolysis in obese
individuals.
PMID- 25132156
TI - Four-component fluorescence of trans-1,2-di(1-methyl-2-naphthyl)ethene at 77 K in
glassy media. Conformational subtleties revealed.
AB - The vibronic structure of the fluorescence spectrum of trans-1,2-di(1-methyl-2
naphthyl)ethene (t-1,1) in methylcyclohexane (MCH) solution at room temperature
was expected to become better defined upon cooling of the solution to 77 K.
Instead, a broad, lambdaexc-dependent fluorescence spectrum was observed in the
glassy medium. Vibronically structured t-1,1 fluorescence spectra were obtained
in the MCH glass only upon irradiation at the long-lambda onset of the absorption
spectrum. The application of singular value decomposition with self-modeling on
the fluorescence spectral matrices of t-1,1 allowed their resolution into major
and minor pairs of vibronically structured spectra that are assigned to two
structural modifications of each of two relative orientations of the 1-methyl-2
naphthyl moieties. The difference between the two structures in each pair lies in
the direction of rotation of each naphthyl group away from the plane of the
olefinic bond. A complex but different conformer distribution is also responsible
for the fluorescence spectra of t-1,1 in 5:5:2 (v/v/v) diethyl
ether/isopentane/ethyl alcohol (EPA) glass at 77 K. The conformer distributions
are also sensitive to the rate of cooling used in glass formation. Conformer
distributions based on predicted small energy differences from gas-phase
theoretical calculations are of little value when applied to volume-constraining
media. The photophysical and photochemical properties of the analogues of the
other two conformers of trans-1,2-di(2-naphthyl)ethene, trans-1-(1-methyl-2
naphthyl)-2-(3-methyl-2-naphthyl)ethene (t-1,3) and trans-1,2-di(3-methyl-2
naphthyl)ethene (t-3,3), were determined in solution. However, it is the
calculated geometries and energy differences of the t-1,1 conformers [DFT using
B3LYP/6-311+G(d,p)] that are essential guides to the interpretation of the
experimental results.
PMID- 25132157
TI - The politics of unsafe abortion in Burkina Faso: the interface of local norms and
global public health practice.
AB - In Burkina Faso, abortion is legally restricted and socially stigmatised, but
also frequent. Unsafe abortions represent a significant public health challenge,
contributing to the country's very high maternal mortality ratio. Inspired by an
internationally disseminated public health framing of unsafe abortion, the
country's main policy response has been to provide post-abortion care (PAC) to
avert deaths from abortion complications. Drawing on ethnographic research, this
article describes how Burkina Faso's PAC policy emerged at the interface of
political and moral negotiations between public health professionals, national
bureaucrats and international agencies and NGOs. Burkinabe decision-makers and
doctors, who are often hostile to induced abortion, have been convinced that PAC
is 'life-saving care' which should be delivered for ethical medical reasons.
Moreover, by supporting PAC they not only demonstrate compliance with
international standards but also, importantly, do not have to contend with any
change in abortion legislation, which they oppose. Rights-based international
NGOs, in turn, tactically focus on PAC as a 'first step' towards their broader
institutional objective to secure safe abortion and abortion rights. Such
negotiations between national and international actors result in widespread
support for PAC but stifled debate about further legalisation of abortion.
PMID- 25132158
TI - Effects of magnesium sulphate on coagulation after laparoscopic colorectal cancer
surgery, measured by rotational thromboelastometry (ROTEM(r) ).
AB - We investigated the effects of magnesium sulphate on blood coagulation profiles
using rotational thromboelastometry in patients undergoing laparoscopic
colorectal cancer surgery. Patients were randomly allocated to the magnesium
group (n = 22) or control group (n = 22). The magnesium group received
intravenous magnesium sulphate (50 mg.kg(-1) followed by a continuous infusion of
15 mg.kg(-1) .h(-1) ), whereas the control group received the same volume of
isotonic saline. Mean (SD) postoperative serum magnesium levels were 1.60 (0.13)
mmol.l(-1) in the magnesium group compared with 0.98 (0.06) mmol.l(-1) in the
control group (p < 0.001). All maximum clot firmness values of ROTEM analysis
were significantly lower on the third postoperative day in the magnesium group
compared with the control group (p < 0.05). We conclude that ROTEM analysis
demonstrated that intra-operative administration of intravenous magnesium
sulphate reduces blood hypercoagulability in patients undergoing laparoscopic
colorectal cancer surgery.
PMID- 25132159
TI - Steroid-induced ocular hypertensive response in children and adolescents with
acute lymphoblastic leukemia and non-Hodgkin lymphoma.
AB - The aim of this study was to evaluate intraocular pressure (IOP) associated with
use of glucocorticoids in children and adolescents treated for acute
lymphoblastic leukemia and non-Hodgkin lymphoma. We carried out a prospective
descriptive study with measurement of IOP before treatment (D0), 8th (D8), 14th
(D14), and 28 h days (D28) of treatment. We examined 12 patients, with two cases
of ocular hypertension, and it was found a statistically significant difference
between the means of IOP between D0 versus D8 and D0 versus D14 (P = 0.013). The
possibility of silent ocular hypertension with irreversible blindness indicates
the need of IOP verification.
PMID- 25132160
TI - Can implanted venous access ports remain patent without maintenance flush-lock?
PMID- 25132161
TI - Multisite phosphorylation of Bcl-2 via protein kinase Cdelta facilitates
apoptosis of hypertrophic cardiomyocytes.
AB - Activated protein kinase Cdelta (PKCdelta) associated with cardiac hypertrophy
moves from the cytoplasm to the mitochondria and subsequently triggers the
apoptotic signalling pathway. The underlying mechanisms remain unknown. The aim
of the present study was to investigate whether mitochondrial translocation of
PKCdelta phosphorylates multiple sites of Bcl-2, resulting in an imbalance
between Bcl-2 and Bak or Bax, thus enhancing the susceptibility of hypertrophic
cardiomyocytes to angiotensin II (AngII)-induced apoptosis. Chronic pressure
overload was induced by transverse aortic constriction (TAC) in rats. The
apoptotic rate increased in hypertrophied cardiomyocytes. In AngII-treated hearts
(10 nmol/L, 60 min), there was an increase in the number of TERMINAL
deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling
(TUNEL)-positive cells; PKCdelta inhibition with 500 nmol/L deltaV1-1 for 60 min
prevented the AngII-induced increase in apoptosis. In the hypertrophied
myocardium, PKCdelta expression increased, whereas that of Bcl-2 decreased
compared with the synchronous control. Treatment of hearts with 10 nmol/L AngII
for 60 min activated PKCdelta and induced translocation of PKCdelta to the
mitochondria, where activated PKCdelta facilitated the phosphorylation of Bcl-2
at serine-87 and serine-70 sites. The multisite phosphorylated Bcl-2 was released
from the mitochondria, and exhibited reduced affinity for Bak and Bax. The
imbalance between Bcl-2 and Bak/Bax induced the release of mitochondrial
cytochrome c and then activated the caspase 3 apoptotic pathway during AngII
stimulation (10 nmol/L, 60 min) of hypertrophied cardiomyocytes. Inhibition of
PKCdelta reduced these effects of AngII. The results suggest that PKCdelta can
counteract the anti-apoptotic effect of Bcl-2 and may promote cardiomyocyte
apoptosis through multisite phosphorylation of Bcl-2 in hypertrophied
cardiomyocytes.
PMID- 25132162
TI - HPV and Chlamydia trachomatis co-detection in young asymptomatic women from high
incidence area for cervical cancer.
AB - Chlamydia trachomatis causing chronic inflammatory diseases has investigated as
possible human papillomavirus (HPV) cofactor in cervical cancer. The aim of this
study is to evaluate the prevalence of Chlamydia trachomatis and HPV co-infection
in different cohorts of asymptomatic women from a Northern Italy area at high
incidence for cervical cancer. Cervical samples from 441 females were collected
from Cervical Cancer Screening Program, Sexually Transmitted Infectious and
Assisted Reproductive Technology centres. HPV and Chlamydia trachomatis were
detected simultaneously and genotyped using a highly sensitive bead based assay.
The overall prevalence of Chlamydia trachomatis was estimated 9.7%, in contrast
with the reported national data of 2.3%, and co-infection with HPV was diagnosed
in the 17% of the samples. In females <= 25 years of age, the infection reached a
peak of 22% and co-infection with HPV of 45.8% (P < 0.001). Of note, in young
females diagnosed with low grade cervical lesions, no significant difference
between Chlamydia trachomatis and HPV distribution was observed, while
differently, HPV co-infection was found significantly associated to the presence
of intraepithelial lesions when compared to older females (20% vs. 1%; P <
0.001). In this study, the use of a high sensitive molecular technique exhibited
higher analytical sensitivity than the referred assays for the diagnosis of
Chlamydia trachomatis and HPV co-infection in asymptomatic females, leading to
reduction of the potential to identify incorrectly the infection status. An
active screening for timely treatment of Chlamydia trachomatis infection is
suggested in young females to evaluate a possible decrease in incidence of pre
cancer intraepithelial lesions.
PMID- 25132163
TI - Multidisciplinary consensus: a practical guide for the integration of abiraterone
into clinical practice.
AB - Abiraterone improves survival, relieves pain, improves quality of life and
extends time to prostate-specific antigen (PSA) progression in patients with
metastatic castration-resistant prostate cancer (mCRPC). A consensus-based guide
for using abiraterone in patients with mCRPC has been developed by Australian
clinicians with expertise in prostate cancer, based on their experience and
supported by published data. Recommendations were developed for eight key topics:
abiraterone administration; steroid administration and duration of use;
concomitant medications and drug interactions; timing of testing and monitoring
response; safety in different populations; potential toxicities; precautions and
contraindications; and referral and multidisciplinary care. Abiraterone is taken
orally in a fasting state. Symptoms associated with mineralocorticoid excess are
managed by coadministration of low-dose prednisone or prednisolone. Potassium
levels, blood pressure and liver function need to be tested frequently during the
early treatment phase. Response to treatment is monitored based on symptoms,
radiological imaging and PSA levels. Potential adverse consequences of long-term
steroid therapy on bone and metabolic health need to be screened for and managed.
Advanced prostate cancer is best managed by a multidisciplinary team and early
referral should be considered. Questions about the potential use of abiraterone
in early disease and in combination with other therapies are being addressed in
ongoing clinical trials.
PMID- 25132164
TI - Retrospective clinical evaluation of hypobaric spinal anaesthesia in dogs
undergoing pelvic limb orthopaedic surgery.
AB - OBJECTIVE: To evaluate intraoperative effects, complications, postoperative
rescue analgesia requirement and presence of postoperative unilateral blockade
after hypobaric spinal anaesthesia in dogs. METHODS: Retrospective review of case
records of dogs that underwent pelvic limb orthopaedic surgery and received
hypobaric spinal anaesthesia. Cases that contained complete information on
perioperative analgesia, end tidal anaesthetic agent, arterial blood pressure,
postoperative urination, motor function and assessment at the sixth week re
examination were selected. RESULTS: Twenty-four of forty-eight records were
sufficiently complete to meet the selection criteria. Local anaesthetic dose and
volume of the solution administered were 0 . 22 (+/-0 . 06) mg/kg and 0 . 16 (+/
0 . 05) mL/kg, respectively. Fentanyl was administered intraoperatively in seven
dogs (29%); mean +/- sd end-expired isoflurane was 1 . 09 +/- 0 . 17%;
hypotension was observed in nine dogs (37 . 5%). Unilateral blockade was
documented in 18 dogs (75%); 6 dogs (25%) required methadone postoperatively;
urinary retention was not observed. One dog developed steroid responsive
meningitis arteritis. CLINICAL SIGNIFICANCE: Hypobaric spinal anaesthesia
achieved unilateral postoperative pelvic limb motor blockade in dogs, although
bilateral block occurred in a proportion of animals; intraoperative hypotension
was not infrequent. Fentanyl and postoperative methadone might be required to
control nociception and pain, despite technical success in performing spinal
anaesthesia.
PMID- 25132165
TI - Reproductive factors and non-Hodgkin lymphoma: a systematic review.
AB - Considerable efforts have been made to elucidate non-Hodgkin lymphoma's (NHL)
etiology during the last decades. Some evidence points to an association with
reproductive factors, as incidence rates for most NHL subtypes are usually higher
in men than in women, and several subtypes express hormonal receptors. Although
the evidence is not compelling, some studies show an inverse association with
gravidity. Associations with postmenopausal hormone therapy are usually derived
from unopposed estrogen use, rather than for the combination of estrogen with
progestin, but these findings vary by study design. Inconsistencies in the
results are likely due to the complex relationship between reproductive,
biological, and sociodemographic factors, as well as to study limitations.
Elucidating the role of hormonal factors should provide clues for therapeutic
options and public health decisions. We provide an overview of the available
evidence on reproductive factors in NHL etiology, underscoring potential sources
of discrepancies and bias.
PMID- 25132166
TI - Diffusion-weighted MR imaging of the rectum: clinical applications.
AB - Dramatic advances in image quality over the past few years have made diffusion
weighted magnetic resonance imaging (DW-MRI) a promising tool for rectal lesion
evaluation. DW-MRI derives its image contrast from differences in the motion of
water molecules between tissues. Such imaging can be performed quickly without
the need for the administration of exogenous contrast medium. The technique
yields qualitative and quantitative information that reflects changes at a
cellular level and provides information about tumor cellularity and the integrity
of cell membranes. The sensitivity to diffusion is obtained by applying two
bipolar diffusion-sensitizing gradients to a standard T2-weighted spin echo
sequence. The diffusion-sensitivity can be varied by adjusting the "b-factor",
which represents the gradient duration, gradient amplitude and the time interval
between the two gradients. The higher the b-value, the greater the signal
attenuation from moving water protons. In this review, technical considerations
relatively to image acquisition and to quantification methods applied to rectal
DW-MRI are discussed. The current clinical applications of DW-MRI, either in the
field of inflammatory or neoplastic rectal disease are reviewed. Also,
limitations, mainly in terms of persistent lack of standardization or evaluation
of tumoral response, and future directions of rectal DW-MRI are discussed. The
potential utility of DW-MRI for the evaluation of rectal tumor response is on its
way to being admitted but future well-designed and multicenter studies, as well
as standardization of DW-MRI, are still required before a consensus can be
reached upon how and when to use DW-MRI.
PMID- 25132167
TI - Challenges and solutions for joining polymer materials.
AB - The different mechanisms contributing to adhesion between two polymer surfaces
are summarized and described in individual examples, which represent either
seminal works in the field of adhesion science or novel approaches to achieve
polymer-polymer adhesion. A further objective of this article is the development
of new methodologies to achieve strong adhesion between low surface energy
polymers.
PMID- 25132168
TI - Clinical use of computed tomography and surface markers to assist internal
fixation within the equine hoof.
AB - OBJECTIVE: To describe clinical use of computed tomography (CT) and hoof surface
markers to facilitate internal fixation within the confines of the hoof wall.
STUDY DESIGN: Retrospective case series. ANIMALS: Horses (n = 16) that had CT
guided internal fixation of the distal phalanx (DP) or distal sesamoid bone
(DSB). METHODS: Drill bit entry point and direction were planned from CT image
series performed on hooves with grids of barium paste dots at proposed entry and
projected exit sites. Post-implantation CT images were obtained to check screw
position and length as well as fracture reduction. Imaging, reduction, and
surgical and general anesthesia times were evaluated. Outcome was recorded.
RESULTS: Screw position and length were considered near optimal in all horses,
with no consequential malposition of bits or screws. Fracture reduction was
evident in all cases. Preoperative planning times (at least 2 CT image
acquisitions and grid creation) ranged from 10 to 20 minutes. Surgery time ranged
from 45 to 90 minutes (mean, 61 minutes) and general anesthesia time ranged from
115 to 220 minutes (mean, 171 minutes). CONCLUSIONS: The combination of CT and
surface marker grids allowed accurate positioning of screws in clinical DP and
DSB fractures. The technique was simple and rapid. An aiming device is useful for
the technique.
PMID- 25132169
TI - Surgical management of well-differentiated thyroid carcinoma in children and
adolescents: 33 years of experience of a single institution in Serbia.
AB - Well-differentiated thyroid carcinoma in children and adolescents is rare but
demonstrates aggressive behavior. Gross lymph node metastases and distant
metastases are common upon first clinical presentation. During a 33-year period
(1981-2014) at the Institute of Oncology and Radiology of Serbia, 62 children and
adolescents underwent surgery due to well-differentiated thyroid carcinoma. Mean
age was 16.7 (range 7-21) years. At the time of diagnosis 6% of patients had lung
metastases. Total thyroidectomy or completion thyroidectomy was performed for all
patients followed by central neck dissection and frozen section examination of
jugular-carotid compartments. Median follow-up was 10.9 (range 0.69-33.05) years
and median tumor size was 20 (range 2-60) mm. Papillary carcinoma was found in
96%, and follicular and Hurthle cell carcinoma in 2% of patients. Multifocal
tumors were found in 50% and capsular invasion in 60% of patients. Lymphonodal
metastases in either central or lateral neck compartments were found in 73% of
patients. Multifocality and capsular invasion were significantly more frequent in
patients less than 16 years of age (both p < 0.01). Median disease-free interval
had not been reached and overall survival rate was 100%. Well-differentiated
thyroid carcinoma in children and adolescents is characterized by a high rate of
loco-regional aggressiveness, multifocality, capsular invasion, lymph node
metastases and distant metastases at the time of diagnosis. Adequate surgical
approaches should be performed for both primary and recurrent disease in young
patients with well-differentiated thyroid carcinoma in order to achieve loco
regional disease control and longer disease-free survival.
PMID- 25132170
TI - Association of osteoporosis susceptibility genes with bone mineral density and
bone metabolism related markers in Koreans: the Chungju Metabolic Disease Cohort
(CMC) study.
AB - In this study, we evaluated the association between bone mineral density (BMD)
and 10 single-nucleotide polymorphisms (SNPs) within eight osteoporosis
susceptibility genes that were previously identified in genome-wide association
studies (GWASs). A total of 494 men and 493 postmenopausal women participating in
the Chungju Metabolic Disease cohort study in Korea were included. The following
10 SNPs were genotyped: ZBTB40 rs6426749, MEF2C rs1366594, ESR1 rs2941740,
TNFRSF11B rs3134070, TNFRSF11B rs2073617, SOX6 rs711785, LRP5 rs599083, TNFSF11
rs227438, TNFSF11 rs9594782, and FOXL1 rs10048146; and the association between
these SNPs and bone metabolism-related markers was assessed. Two SNPs, TNFSF11
rs2277438 and FOXL1 rs1004816, were associated with lumbar spine BMD. TNFSF11
rs2277438 in men and SOX6 rs7117858 and FOXL1 rs10048146 in postmenopausal women
were found to be associated with lumbar BMD. ZBTB40 rs6426749, MEF2C rs1366594,
and LRP5 rs599083 showed significant associations with femur neck BMD. These
three SNPs in men and MEF2C rs1366594 and ESR1 rs2941740 in postmenopausal women
were associated with femur neck BMD. A significant association between MEF2C
rs1366594 and serum calcium levels was observed in men. Serum phosphorus levels
were related to SOX6 rs7117858. Serum PTH levels were significantly associated
with TNFRSF11B rs3134070 in men, and SOX6 rs711858 in postmenopausal women. In
conclusion, our study independently confirmed associations between several SNPs:
ZBTB40, MEF2C, ESR1, SOX6, LRP5, TNFSF11, and FOXL1 and bone marrow density in
the Korean population.
PMID- 25132171
TI - Thyroid storm induced by TSH-secreting pituitary adenoma: a case report.
AB - Thyroid stimulating hormone-secreting pituitary adenomas (TSHomas) are uncommon
tumors of the anterior pituitary gland. Patients with TSHomas may present with
hyperthyroidism, but the incidence of thyroid storm due to TSHomas has yet to be
determined. We report a rare case of thyroid storm caused by TSHoma in a 54-year
old woman. Preoperatively she had symptoms of excessive sweating and palpitation.
Blood tests showed inappropriate secretion of TSH with blood TSH 6.86 MU U/mL,
fT3 19.8 pg/mL, and fT4 5.95 ng/dL. Magnetic resonance imaging (MRI) revealed a
pituitary tumor with maximum diameter of 13 mm that was extirpated through
transsphenoidal route. After operation the patient was stuporous and thyroid
storm occurred presenting with hyperthermia, hypertension, and tachycardia. It
was well managed with nicardipine, midazolam, steroids, and potassium iodide.
Immunohistochemical staining of tumor specimen was positive for TSH and growth
hormone (GH). One year after operation, fT3 and fT4 levels were still high. As
her tumor was diagnosed to be GH- and TSH-producing adenoma, octreotide injection
therapy was started, which normalized thyroid hormone levels. This is the second
reported case with thyroid storm due to TSHoma and emphasizes the importance of
strategies with interdisciplinary cooperation for prevention of such emergency
conditions.
PMID- 25132172
TI - Reconstitution of a minimal ribosome-associated ubiquitination pathway with
purified factors.
AB - Ribosomes stalled on aberrant mRNAs engage quality control mechanisms that
degrade the partially translated nascent polypeptide. Ubiquitination of the
nascent protein is mediated by the E3 ligase Listerin via a mechanism involving
ribosome subunit dissociation. Here, we reconstitute ribosome-associated
ubiquitination with purified factors to define the minimal components and
essential steps in this process. We find that the primary role of the ribosome
splitting factors Hbs1, Pelota, and ABCE1 is to permit Listerin access to the
nascent chain. Listerin alone can discriminate 60S- from 80S-nascent chain
complexes to selectively ubiquitinate the former. Splitting factors can be
bypassed by artificially removing the 40S subunit, suggesting that mere steric
hindrance impedes Listerin recruitment. This was illustrated by a cryo-EM
reconstruction of the 60S-Listerin complex that identifies a binding interface
that clashes with the 40S ribosomal subunit. These results reveal the mechanistic
logic of the core steps in a ribosome-associated quality control pathway.
PMID- 25132173
TI - NuA4 initiates dynamic histone H4 acetylation to promote high-fidelity sister
chromatid recombination at postreplication gaps.
AB - CAG/CTG trinucleotide repeats are unstable, fragile sequences that strongly
position nucleosomes, but little is known about chromatin modifications required
to prevent genomic instability at these or other structure-forming sequences. We
discovered that regulated histone H4 acetylation is required to maintain CAG
repeat stability and promote gap-induced sister chromatid recombination. CAG
expansions in the absence of H4 HATs NuA4 and Hat1 and HDACs Sir2, Hos2, and Hst1
depended on Rad52, Rad57, and Rad5 and were therefore arising through homology
mediated postreplication repair (PRR) events. H4K12 and H4K16 acetylation were
required to prevent Rad5-dependent CAG repeat expansions, and H4K16 acetylation
was enriched at CAG repeats during S phase. Genetic experiments placed the RSC
chromatin remodeler in the same PRR pathway, and Rsc2 recruitment was coincident
with H4K16 acetylation. Here we have utilized a repetitive DNA sequence that
induces endogenous DNA damage to identify histone modifications that regulate
recombination efficiency and fidelity during postreplication gap repair.
PMID- 25132174
TI - Histone-fold domain protein NF-Y promotes chromatin accessibility for cell type
specific master transcription factors.
AB - Cell type-specific master transcription factors (TFs) play vital roles in
defining cell identity and function. However, the roles ubiquitous factors play
in the specification of cell identity remain underappreciated. Here we show that
the ubiquitous CCAAT-binding NF-Y complex is required for the maintenance of
embryonic stem cell (ESC) identity and is an essential component of the core
pluripotency network. Genome-wide studies in ESCs and neurons reveal that NF-Y
regulates not only genes with housekeeping functions through cell type-invariant
promoter-proximal binding, but also genes required for cell identity by binding
to cell type-specific enhancers with master TFs. Mechanistically, NF-Y's distinct
DNA-binding mode promotes master/pioneer TF binding at enhancers by facilitating
a permissive chromatin conformation. Our studies unearth a conceptually unique
function for histone-fold domain (HFD) protein NF-Y in promoting chromatin
accessibility and suggest that other HFD proteins with analogous structural and
DNA-binding properties may function in similar ways.
PMID- 25132175
TI - Genome-wide Hi-C analyses in wild-type and mutants reveal high-resolution
chromatin interactions in Arabidopsis.
AB - Chromosomes form 3D structures that are critical to the regulation of cellular
and genetic processes. Here, we present a study of global chromatin interaction
patterns in Arabidopsis thaliana. Our genome-wide approach confirmed interactions
that were previously observed by other methods as well as uncovered long-range
interactions such as those among small heterochromatic regions embedded in
euchromatic arms. We also found that interactions are correlated with various
epigenetic marks that are localized in active or silenced chromatin. Arabidopsis
chromosomes do not contain large local interactive domains that resemble the
topological domains described in animals but, instead, contain relatively small
interactive regions scattered around the genome that contain H3K27me3 or H3K9me2.
We generated interaction maps in mutants that are defective in specific
epigenetic pathways and found altered interaction patterns that correlate with
changes in the epigenome. These analyses provide further insights into molecular
mechanisms of epigenetic regulation of the genome.
PMID- 25132176
TI - Hi-C analysis in Arabidopsis identifies the KNOT, a structure with similarities
to the flamenco locus of Drosophila.
AB - Chromosomes are folded, spatially organized, and regulated by epigenetic marks.
How chromosomal architecture is connected to the epigenome is not well
understood. We show that chromosomal architecture of Arabidopsis is tightly
linked to the epigenetic state. Furthermore, we show how physical constraints,
such as nuclear size, correlate with the folding principles of chromatin. We also
describe a nuclear structure, termed KNOT, in which genomic regions of all five
Arabidopsis chromosomes interact. These KNOT ENGAGED ELEMENT (KEE) regions
represent heterochromatic islands within euchromatin. Similar to PIWI-interacting
RNA clusters, such as flamenco in Drosophila, KEEs represent preferred landing
sites for transposable elements, which may be part of a transposon defense
mechanism in the Arabidopsis nucleus.
PMID- 25132177
TI - Structures of CRISPR Cas3 offer mechanistic insights into Cascade-activated DNA
unwinding and degradation.
AB - CRISPR drives prokaryotic adaptation to invasive nucleic acids such as phages and
plasmids, using an RNA-mediated interference mechanism. Interference in type I
CRISPR-Cas systems requires a targeting Cascade complex and a degradation
machine, Cas3, which contains both nuclease and helicase activities. Here we
report the crystal structures of Thermobifida fusca Cas3 bound to single-stranded
(ss) DNA substrate and show that it is an obligate 3'-to-5' ssDNase that
preferentially accepts substrate directly from the helicase moiety. Conserved
residues in the HD-type nuclease coordinate two irons for ssDNA cleavage. We
demonstrate ATP coordination and conformational flexibility of the SF2-type
helicase domain. Cas3 is specifically guided toward Cascade-bound target DNA by a
PAM sequence, through physical interactions with both the nontarget substrate
strand and the CasA protein. The sequence of recognition events ensures well
controlled DNA targeting and degradation of foreign DNA by Cascade and Cas3.
PMID- 25132178
TI - RBFOX and SUP-12 sandwich a G base to cooperatively regulate tissue-specific
splicing.
AB - Tissue-specific alternative pre-mRNA splicing is often cooperatively regulated by
multiple splicing factors, but the structural basis of cooperative RNA
recognition is poorly understood. In Caenorhabditis elegans, ligand binding
specificity of fibroblast growth factor receptors (FGFRs) is determined by
mutually exclusive alternative splicing of the sole FGFR gene, egl-15. Here we
determined the solution structure of a ternary complex of the RNA-recognition
motif (RRM) domains from the RBFOX protein ASD-1, SUP-12 and their target RNA
from egl-15. The two RRM domains cooperatively interact with the RNA by
sandwiching a G base to form the stable complex. Multichromatic fluorescence
splicing reporters confirmed the requirement of the G and the juxtaposition of
the respective cis elements for effective splicing regulation in vivo. Moreover,
we identified a new target for the heterologous complex through an element
search, confirming the functional significance of the intermolecular
coordination.
PMID- 25132179
TI - A proton wire to couple aminoacyl-tRNA accommodation and peptide-bond formation
on the ribosome.
AB - During peptide-bond formation on the ribosome, the alpha-amine of an aminoacyl
tRNA attacks the ester carbonyl carbon of a peptidyl-tRNA to yield a peptide
lengthened by one amino acid. Although the ribosome's contribution to catalysis
is predominantly entropic, the lack of high-resolution structural data for the
complete active site in complex with full-length ligands has made it difficult to
assess how the ribosome might influence the pathway of the reaction. Here, we
present crystal structures of preattack and postcatalysis complexes of the
Thermus thermophilus 70S ribosome at ~2.6-A resolution. These structures reveal a
network of hydrogen bonds along which proton transfer could take place to ensure
the concerted, rate-limiting formation of a tetrahedral intermediate. We propose
that, unlike earlier models, the ribosome and the A-site tRNA facilitate the
deprotonation of the nucleophile through the activation of a water molecule.
PMID- 25132182
TI - Travelling with medications and medical equipment across international borders.
AB - The international traveller needs to plan ahead to ensure medicines are available
and used as directed for optimal therapeutic outcome. The planning needs to take
account of legal and customs requirements for travelling with medicines for
personal use. The standard advice by travel health providers is that travellers
should check with the country of destination for requirements when travelling
into the country with medicines for personal use. This is akin to introducing a
barrier to care for this category of travellers. Innovative method of care for
this group of traveller is needed.
PMID- 25132180
TI - Architecture of the Saccharomyces cerevisiae RNA polymerase I Core Factor
complex.
AB - Core Factor (CF) is a conserved RNA polymerase (Pol) I general transcription
factor comprising Rrn6, Rrn11 and the TFIIB-related subunit Rrn7. CF binds TATA
binding protein (TBP), Pol I and the regulatory factors Rrn3 and upstream
activation factor. We used chemical cross-linking-MS to determine the molecular
architecture of CF and its interactions with TBP. The CF subunits assemble
through an interconnected network of interactions between five structural domains
that are conserved in orthologous subunits of the human Pol I factor SL1. We
validated the cross-linking-derived model through a series of genetic and
biochemical assays. Our combined results show the architecture of CF and the
functions of the CF subunits in assembly of the complex. We extend these findings
to model how CF assembles into the Pol I preinitiation complex, providing new
insight into the roles of CF, TBP and Rrn3.
PMID- 25132181
TI - Repetitive sequences in plant nuclear DNA: types, distribution, evolution and
function.
AB - Repetitive DNA sequences are a major component of eukaryotic genomes and may
account for up to 90% of the genome size. They can be divided into minisatellite,
microsatellite and satellite sequences. Satellite DNA sequences are considered to
be a fast-evolving component of eukaryotic genomes, comprising tandemly-arrayed,
highly-repetitive and highly-conserved monomer sequences. The monomer unit of
satellite DNA is 150-400 base pairs (bp) in length. Repetitive sequences may be
species- or genus-specific, and may be centromeric or subtelomeric in nature.
They exhibit cohesive and concerted evolution caused by molecular drive, leading
to high sequence homogeneity. Repetitive sequences accumulate variations in
sequence and copy number during evolution, hence they are important tools for
taxonomic and phylogenetic studies, and are known as "tuning knobs" in the
evolution. Therefore, knowledge of repetitive sequences assists our understanding
of the organization, evolution and behavior of eukaryotic genomes. Repetitive
sequences have cytoplasmic, cellular and developmental effects and play a role in
chromosomal recombination. In the post-genomics era, with the introduction of
next-generation sequencing technology, it is possible to evaluate complex genomes
for analyzing repetitive sequences and deciphering the yet unknown functional
potential of repetitive sequences.
PMID- 25132183
TI - Molecular characterization of oxytocin receptor gene in water buffalo (Bubalus
bubalis).
AB - Buffaloes are known for their productivity as compared to average yielding cows
due to higher fat percentage, better feed conversion ability and disease
resistance. On the other hand, the reproductive performances of buffaloes are
often considered as poor owing to late sexual maturity, weak/silent oestrus,
repeat breeder and prolonged intercalving interval. The study of cascade of
events during oestrus and oestrous cycle can be useful for the improvement of
reproductive efficiency of buffaloes. More precisely, the hormonal changes
initiated at the molecular level within the animal determine the reproductive
nature of the species. Nucleotide/protein sequence analysis serves as a vital
tool in analysing the binding of the hormones for their effect or functions. In
this study, we have reported cloning and characterization of the complete coding
(cDNA) sequence of oxytocin receptor gene (OXTR) in buffaloes. Buffalo OXTR gene
contains an uninterrupted ORF of 1176 nucleotides corresponding to an inferred
polypeptide length of 391 amino acids (aa). The molecular weight of the deduced
aa sequence was found to be 43 kDa with an isoelectric point of 9.253 and 16.328
charge at pH 7.0. The deduced protein sequence consists of 38 strongly basic (+)
(K,R), 22 strongly acidic (-) (D,E), 186 hydrophobic (A, I, L, F, W, V) and 95
Polar (N, C, Q, S, T, Y) aa. Results indicated that aspartate (D) at aa position
85 and D, R and C at aa positions 136, 137 and 138, respectively, are conserved
in buffaloes. The buffalo OXTR gene shared a per cent similarity ranging from
84.7 to 98.1 and 88.5 to 97.7 at nucleotide and deduced aa sequence levels,
respectively, with that of other species. Phylogram constructed on the basis of
either nucleotide or deduced aa sequences of buffalo OXTR gene showed that
buffalo, cattle and sheep have diverged from human and swine and formed a
separate clad. The buffalo sequence has shown maximum similarity and closeness
with cattle followed by sheep both at nucleotide and at aa level.
PMID- 25132184
TI - Theoretical study on molecular structure and vibrational analysis included FT-IR,
FT-Raman and UV techniques of 2,4,5-trimethylbenzoic acid (monomer and dimer
structures).
AB - Theoretical study on the structural and vibrational analysis of monomer and dimer
structures of 2,4,5-trimethylbenzoic acid (2,4,5-TMBA, C10H12O2) were presented.
The geometry of the molecule was fully optimized. The Fourier transform infrared
(FT-IR) and the Fourier transform Raman (FT-Raman) spectra of the title molecule
in solid phase were recorded in the region 4000-400 cm(-1) and 4000-50 cm(-1),
respectively. The geometrical parameters and energies were investigated with the
help of Density Functional Theory (DFT) employing B3LYP method and 6-311++G(d,p)
basis set. The spectroscopic data of the molecule in the ground state were
calculated by using DFT/B3LYP method with the 6-311++G(d,p) basis set. The
vibrational spectra were calculated and fundamental vibrations were assigned on
the basis of the potential energy distribution (PED) of the vibrational modes.
The geometric parameters were compared with experimental data of the title
molecule. The UV absorption spectrum of the studied compound was computed and
recorded in the range of 190-400 nm dissolved in water and ethanol. Besides,
charge transfer occurring in the molecule between HOMO and LUMO energies,
frontier energy gap, molecular electrostatic potential (MEP) were calculated and
presented. In addition these, thermodynamic properties and Mulliken atomic
charges were performed.
PMID- 25132185
TI - Common ENT disorders in pediatrics.
PMID- 25132187
TI - Is surgical removal of the noncompacted layer the clue to treat left ventricular
hypertrabeculation/noncompaction?
PMID- 25132186
TI - Dumping syndrome with severe hipoglycemia after Nissen fundoplication in adults.
Case report and literature review.
PMID- 25132188
TI - Exercise tolerance in obese vs. lean adolescents: a systematic review and meta
analysis.
AB - To prescribe feasible and medically safe exercise interventions for obese
adolescents, it remains to be determined whether exercise tolerance is altered
and whether anomalous cardiopulmonary responses during maximal exercise testing
are present. Studies that examined cardiopulmonary responses to maximal exercise
testing in obese adolescents were searched: cardiopulmonary exercise tests with
respiratory gas exchange measurements of peak oxygen uptake (VO2peak) were
performed and comparisons between obese and lean adolescents were made. Study
quality was assessed using a standardized item list. By meta-analyses VO2peak,
peak cycling power output (Wpeak) and peak heart rate (HRpeak) were compared
between groups. Nine articles were selected (333 obese vs. 145 lean adolescents).
VO2peak (L min(-1)), HRpeak and Wpeak were not different between groups (P >=
0.10), while a trend was found for a reduced VO2peak (mL min(-1) kg(-1) lean
tissue mass) (P=0.07) in obese vs. lean adolescents. It remained uncertain
whether anomalous cardiopulmonary responses occur during maximal exercise testing
in obese adolescents. In conclusion, a trend was found for lowered VO2peak (mL
min(-1)kg(-1) lean tissue mass) in obese vs. lean adolescents. Whether
cardiopulmonary anomalies during maximal exercise testing would occur in obese
adolescents remains uncertain. Studies are therefore warranted to examine the
cardiopulmonary response during maximal exercise testing in obese adolescents.
PMID- 25132189
TI - iPSC Transplantation increases regeneration and functional recovery after
ischemic stroke in neonatal rats.
AB - Limited treatments are available for perinatal/neonatal stroke. Induced
pluripotent stem cells (iPSCs) hold therapeutic promise for stroke treatment, but
the benefits of iPSC transplantation in neonates are relatively unknown. We
hypothesized that transplanted iPSC-derived neural progenitor cells (iPSC-NPCs)
would increase regeneration after stroke. Mouse pluripotent iPSCs were
differentiated into neural progenitors using a retinoic acid protocol.
Differentiated neural cells were characterized by using multiple criteria and
assessments. Ischemic stroke was induced in postnatal day 7 (P7) rats by
occluding the right middle cerebral artery and right common carotid artery. iPSC
NPCs (400,000 in 4 ul) were transplanted into the penumbra via intracranial
injection 7 days after stroke. Trophic factor expression in the peri-infarct
tissue was measured using Western blot analysis. Animals received daily
bromodeoxyuridine (BrdU) injections and were sacrificed 21 days after stroke for
immunohistochemistry. The vibrissae-elicited forelimb placement test was used to
evaluate functional recovery. Differentiated iPSCs expressed mature neuronal
markers, functional sodium and potassium channels, and fired action potentials.
Several angiogenic and neurogenic trophic factors were identified in iPSC-NPCs.
Animals that received iPSC-NPC transplantation had greater expression of stromal
cell-derived factor 1-alpha (SDF-1alpha) and vascular endothelial growth factor
(VEGF) in the peri-infarct region. iPSC-NPCs stained positive for neuronal nuclei
(NeuN) or glial fibrillary acidic protein (GFAP) 14 days after transplantation.
iPSC-NPC-transplanted animals showed greater numbers of BrdU/NeuN and
BrdU/Collagen IV colabeled cells in the peri-infarct area compared with stroke
controls and performed better in a sensorimotor functional test after stroke.
iPSC-NPC therapy may play multiple therapeutic roles after stroke by providing
trophic factors, increasing angiogenesis and neurogenesis, and providing new
cells for tissue repair.
PMID- 25132190
TI - A novel treatment for propagated crown fractures.
AB - INTRODUCTION: A major complication after endodontic treatment is persistent pain
on biting or chewing. Although unsuccessful endodontic treatment can account for
such pain, pain to chewing and biting can also be a result of an unsupported or
propagated crown fracture. Crown fractures that extend apically result in
deterioration of the localized periodontium and ultimate loss of the tooth. To
date, no predictable treatment for apically extending crown fractures exists.
METHODS: Three cases of nonsurgical excision of a propagated crown fracture and
the repair of the subsequent iatrogenic perforation are presented.
RESULTS/CONCLUSIONS: This case report series describes a novel treatment for
apically progressive crown fractures that results in patient comfort and
maintenance as well as improved periodontal status of the tooth.
PMID- 25132191
TI - Automated Competitive Protein-Binding Assay for Total 25-OH Vitamin D,
Multicenter Evaluation and Practical Performance.
AB - BACKGROUND: The Roche Elecsys Vitamin D Total competitive protein-binding assay
uses recombinant vitamin D binding protein for measuring 25-hydroxyvitamin D (25
OHD), which is different from commonly used antibody assays. METHODS: The assay,
standardized against LC-MS/MS, was tested at four sites. Evaluation included
precision; between-laboratory variability; functional sensitivity; correlation to
LC-MS/MS, HPLC, and immunoassays; as well as robustness, traceability, and EQAS
performance. RESULTS: Precision testing showed within-run coefficient of
variations (CVs) of <= 7%, within-laboratory CVs of <9.5%, between-laboratory
precision CVs of <= 10.1%, and a functional sensitivity below 9.8 nmol/l (at CV
12.9%). The assay showed equivalent 25-OHD levels for matched serum and plasma
samples, good reagent lot-to-lot consistency in pooled sera over time, and good
agreement with HPLC (relative bias -8.8%). Comparison with LC-MS/MS methods
yielded relative biases of -15.4, -13.5, -10.2, and 3.2%. Comparison against
immunoassays showed a relative bias of 14.5% (DiaSorin Liaison) and -58.2% (IDS
iSYS). The overall mean results in 2 years DEQAS was 102% of the ALTM. In a
certified reference patient panel, the average bias was < 4% for the sum of 25
OHD2 and 25-OHD3. CONCLUSION: The Elecsys Vitamin D Total assay demonstrated good
overall performance and is, according to present standards, very suitable for
automated measurement of 25-OHD.
PMID- 25132192
TI - Recovery of the response to biological treatments using narrow band ultraviolet-B
in patients with moderate to severe psoriasis: a retrospective study of 17
patients.
AB - BACKGROUND/PURPOSE: Biological therapy has demonstrated a very satisfactory anti
psoriatic effect; however, the loss of response with time has been reported.
OBJECTIVE: To evaluate the efficacy of the narrow band ultraviolet-B phototherapy
(NB-UVB) as a rescue in patients with moderate to severe psoriasis who have lost
efficacy in their biological treatment. METHODS: A retrospective chart review
study was conducted on patients with moderate to severe psoriasis receiving
treatment with a biologic, with a good initial response that subsequently had
lost efficacy. All the patients received combined treatment with NB-UVB. RESULTS:
Seventeen patients were included, with a mean age of 44 years. The biologics
were: 8 etanercept, 4 adalimumab, 3 ustekinumab, 1 efalizumab, and 1 infliximab.
The mean NB-UVB sessions was 25 (7-48 sessions), with a mean accumulated dose of
31.12 J/cm(2) (5.2-94.6 J/cm(2) ). Sixteen patients had the following results:
44% PASI 90-100, 31.3% PASI 75-89, and 25% PASI 50-74 response. CONCLUSION:
According to this study on clinical practice, it could be considered that the use
of NB-UVB along with biological drugs that have lost efficacy in controlling
moderate to severe psoriasis in adults could contribute to the recovery of the
initial response.
PMID- 25132193
TI - Paired box 2 upregulates androgen receptor gene expression in androgen
independent prostate cancer.
AB - Androgen-independent prostate cancer is known as a hormone-refractory disease.
Although the androgen receptor (AR) is considered to be a key regulator of
androgen-independent prostate cancer progression, the mechanism through which AR
gene expression is regulated is not well understood. In the present study, we
showed that the AR gene was upregulated by paired box 2 (PAX2) in androgen
independent prostate cancer. When PAX2 upregulated AR gene expression, a decrease
in DNA methylation of the AR gene locus was also observed. PAX2 was highly
expressed and promoted cell growth in an androgen-independent prostate cancer
cell line (22Rv1). The cell growth inhibition by PAX2 knockdown was rescued by AR
overexpression in 22Rv1 cells. In a mouse xenograft model of androgen-independent
prostate cancer, PAX2 knockdown inhibited tumor growth and AR gene expression and
also increased DNA methylation of the AR gene. Consistent with this, AR and PAX2
expression levels were positively correlated in prostate cancer patients. These
findings suggested that PAX2 promoted cancer cell growth in androgen-independent
prostate cancer by regulating AR gene expression through an epigenetic mechanism.
PMID- 25132194
TI - Twenty-four-hour intraocular pressure patterns in patients with thyroid eye
disease.
AB - BACKGROUND: To prospectively investigate the safety, tolerability and 24-h
intraocular pressure (IOP) patterns in patients with thyroid eye disease (TED)
using a contact lens sensor (CLS). DESIGN: Prospective study. PARTICIPANTS: Ten
patients with established TED. METHODS: Ten eyes of 10 patients were
prospectively evaluated in an ambulatory 24-h IOP monitoring session using the
CLS (Sensimed AG, Lausanne, Switzerland). Patients pursued daily activities, and
sleep behaviour was uncontrolled. MAIN OUTCOME MEASURES: Incidence of adverse
events (AEs) and tolerability (scale of 0-10, increasing intolerance) were
assessed. IOP patterns were evaluated using a cosinor rhythmometry model, and
linear regression slopes were constructed for the transition from wake/sitting
(W/S) to sleep/supine (S/S) and vice versa. RESULTS: Mean age was 61.8 +/- 21.6
years, and 90% of patients were female. Main AEs were blurred vision (50%),
conjunctival hyperaemia (100%) and superficial punctate keratitis (20%).
Tolerability of the lens was found to be 1.5 +/- 0.7. Positive linear slopes of
the CLS signal from wake to sleep were detected (18.0 +/- 43.8 arbitrary units
[a.u.]; P = 0.254), whereas at the transition from S/S to W/S a significant
decrease (-62.9 +/- 56.8 a.u.; P = 0.010) was found. Five patients (50%) had a
significant nocturnal/sleep acrophase with the peak occurring at 6:30 a.m. The
mean amplitude of the 24-h curves was 102.2 +/- 52.6 a.u. CONCLUSIONS: In
patients with TED, the CLS provides a safe and well-tolerated approach to 24-h
IOP monitoring. After modelling the 24-h IOP curves, TED patients were found to
have a morning acrophase.
PMID- 25132195
TI - Size-dependent thermochromism through enhanced electron-phonon coupling in 1 nm
quantum dots.
AB - 1 nm CuO quantum dots (QDs) were produced in size-controlled super-micropores of
a silica matrix. The reversible color change of the QDs from pale blue to deep
green was clearly observed in a wide temperature range from 298 to 673 K. This
particular thermochromism is ascribed to an enhanced bandgap shift depending on
temperature with a strong electron-phonon coupling in the confined space of the 1
nm QDs.
PMID- 25132196
TI - Paleontology and evolution-part II.
PMID- 25132197
TI - Bachmann's bundle and coronary sinus ostial pacing accentuate left atrial
electrical dyssynchrony in an acute canine model.
AB - INTRODUCTION: In patients with intraatrial conduction delay and sinus node (SN)
dysfunction, pacing Bachmann's bundle (BBR) and coronary sinus ostium (CSO) has
been suggested to achieve atrial resynchronization with potential beneficial
impact on atrial fibrillation and diastolic heart failure. Clinical studies have
not shown superiority of one approach. METHODS AND RESULTS: We studied electrical
activation sequence in an open-chest acute canine model of normal atrial function
in 8 mongrel dogs under general anesthesia. Bipolar plunge electrodes were
distributed over the surface of the atria during unifocal pacing, and
intracardiac activation sequence was observed. SN pacing resulted in near
simultaneous activation at midline sites (BBR and CSO); the left atrium (LA) was
activated by anterior and posterior wavefronts simultaneously propagating
septally to laterally and meeting at the low-lateral perimitral LA. Right atrial
appendage (RAA) pacing created intra-RA conduction delay and delayed onset of LA
activation. Pacing from RAA, CSO, and BBR resulted in nonsimultaneous activation
at midline sites and produced an anteroposterior gradient of LA activation. This
phenomenon was seen to the greatest degree with midline pacing and shifted the
site of latest activation away from the low-lateral perimitral LA in all pacing
configurations except SN pacing. CONCLUSION: Pacing-induced intra-LA activation
dispersion is enhanced with midline atrial pacing, and secondarily shifts the
site of latest activation away from the lateral mitral annulus. Measuring atrial
activation times to the low-lateral perimitral LA can underestimate the degree of
atrial dyssynchrony and be misinterpreted as atrial synchrony. Establishing
clinical impact requires evaluation of human data.
PMID- 25132198
TI - Onychomadesis: literature review.
AB - Onychomadesis is characterized by separation of the nail plate from the matrix
with persistent attachment to the nail bed and often, but not always, eventual
shedding. Onychomadesis has been associated with infection, autoimmune disease,
critical illness and medications. To our knowledge a literature review of all
associations with onychomadesis has not been completed previously. Most commonly,
onychomadesis has been reported in association with pemphigus vulgaris and hand
foot-mouth disease, and following chemotherapy or antiepileptic medications. This
article summarizes these key culprit associations, postulates the pathogenesis of
nail matrix arrest and summarizes the clinical outcomes. We conducted a
retrospective review of cases of onychomadesis reported from January 1960 to
March 2013. Using the PubMed database, the literature was searched using the
following terms: 'onychomadesis' and 'proximal nail shedding'. Also, an Ovid
search was carried out using the same terms. In total 56 articles have been
published, including our previously reported series of idiopathic onychomadesis.
Articles pertaining only to Beau's lines and not true onychomadesis were
excluded. Onychomadesis has been associated with autoimmune disease, other major
medical illness, neonatal illness, medication and infection.
PMID- 25132199
TI - Comparing the trends of elevated blood pressure in appalachian and non
Appalachian regions.
AB - As an established risk factor for cardiovascular disease and stroke, hypertension
risks are often thought to be more prevalent in Appalachian mountain ranges when
compared with other neighboring counterpart regions. This study evaluated blood
pressure (BP) readings among 2358 Kentucky residents attending community stroke
risk screening events held in 15 counties, including nine Appalachian counties
(n=1134) and six non-Appalachian counties (n=1224). With high BP being
operationally defined as >=140/90 mm Hg, 41.5% of Appalachian county residents
had elevated BP compared with 42.6% among those from non-Appalachian counties.
Although the counties with the highest rates of elevated BP did tend to reside in
the Appalachian region, there was no significant difference between rates of
elevated BP in Appalachia vs non-Appalachian counties. This dataset is proposed
as a pilot project to encourage further pursuit of a larger controlled project.
PMID- 25132200
TI - EEG-based monitor on anti-nociception during general anaesthesia: mission
impossible?
PMID- 25132201
TI - Dexmedetomidine does not reduce emergence agitation in adults following
orthognathic surgery.
AB - BACKGROUND: Patients undergoing orthognathic surgery are at high risk of
developing emergence agitation. We hypothesised that a single-dose of
dexmedetomidine would reduce emergence agitation in adults with nasotracheal
intubation after orthognathic surgery. METHODS: Seventy adults (20-45 years old)
undergoing orthognathic surgery were randomly assigned to two groups. Patients
received intravenous dexmedetomidine 1 MUg/kg (dex group) or normal saline
(control group) for 10 min at the end of surgery. Remifentanil was infused at
0.02 MUg/kg/min during emergence in both groups. The severity of emergence
agitation was assessed with the Richmond agitation-sedation scale. Cough,
haemodynamic and respiratory profiles, pain, and time to eye opening were
evaluated. RESULTS: The incidence of emergence agitation was not different
between dex group and control group (38% vs. 47%, P = 0.45). However, severe
cough during emergence was reduced in the dex group (P = 0.04). Tachycardia
during emergence and recovery phases was attenuated in the dex group. The verbal
numeric rating of pain was lower in the dex group. There were no differences in
respiratory rate between the two groups. Time to eye opening was prolonged in the
dex group. CONCLUSION: The addition of a single dose of dexmedetomidine (1
MUg/kg) to low-dose remifentanil infusion did not attenuate emergence agitation
in intubated patients after orthognathic surgery compared with low-dose
remifentanil infusion alone. However, single-dose dexmedetomidine suppressed
coughing, haemodynamic changes, and pain during emergence and recovery phases,
without respiratory depression. Delayed awakening might be associated with this
treatment.
PMID- 25132204
TI - Photoluminescence, chemiluminescence and anodic electrochemiluminescence of
hydrazide-modified graphene quantum dots.
AB - Single-layer graphene quantum dots (SGQDs) were refluxed with hydrazine (N2H4) to
prepare hydrazide-modified SGQDs (HM-SGQDs). Compared with SGQDs, partial oxygen
containing groups have been removed from HM-SGQDs. At the same time, a lot of
hydrazide groups have been introduced into HM-SGQDs. The introduced hydrazide
groups provide HM-SGQDs with a new kind of surface state, and give HM-SGQDs
unique photoluminescence (PL) properties such as blue-shifted PL emission and a
relatively high PL quantum yield. More importantly, the hydrazide-modification
made HM-SGQDs have abundant luminol-like units. Accordingly, HM-SGQDs exhibit
unique and excellent chemiluminescence (CL) and anodic electrochemiluminescence
(ECL). The hydrazide groups of HM-SGQDs can be chemically oxidized by the
dissolved oxygen (O2) in alkaline solutions, producing a strong CL signal. The CL
intensity is mainly dependent on the pH value and the concentration of O2,
implying the potential applications of HM-SGQDs in pH and O2 sensors. The
hydrazide groups of HM-SGQDs can also be electrochemically oxidized in alkaline
solutions, producing a strong anodic ECL signal. The ECL intensity can be
enhanced sensitively by hydrogen peroxide (H2O2). The enhanced ECL intensity is
proportional to the concentration of H2O2 in a wide range of 3 MUM to 500 MUM.
The detection limit of H2O2 was calculated to be about 0.7 MUM. The results
suggest the great potential applications of HM-SGQDs in the sensors of H2O2 and
bio-molecules that are able to produce H2O2 in the presence of enzymes.
PMID- 25132203
TI - Risk of complications due to anticoagulation during dermatosurgical procedures: a
systematic review and meta-analysis.
AB - Background Management of anticoagulation and anti-platelet drugs during cutaneous
surgery is still a challenge for many dermatologists and standards of care with
respect to stopping, continuing or bridging vary widely. Methods We performed a
systematic review (Medline, Cochrane Library, until August 27th, 2013) of studies
assessing the risk of complications due to anticoagulation during cutaneous
surgery. Primary outcomes were mild-moderate and severe postsurgical bleeding.
The secondary outcomes were excessive and uncontrollable intraoperative bleeding
and other postsurgical complications as wound dehiscence, erythema, wound
infection. Results 1.287 publications were identified and 10 studies were
included into the review. The frequencies of bleeding in the control groups in
general were low (about 1%). In patients on aspirin, increased risks were seen
neither with respect to mild-moderate postoperative bleeding (RR 1.1, CI 0.5
2.3), nor with respect to severe bleeding (RR 0.9, CI 0.2-4.6). The studies with
patients on warfarin showed a risk for mild-moderate bleeding that was three
times as high as in controls (RR 3.2, CI 1.4-7.1) and for severe bleeding that
was 15 times higher (RR 14.8, CI 2.7-80.4). In general the study sizes were small
and the methodological quality low. Conclusion The risk of bleeding due to a
medication with aspirin seems to be negligible. With warfarin, the risk is
increased; an exact estimate of the risk increase is difficult to give, because
of the lack of sufficient high quality studies. A two-fold increase appears
likely, the 15-fold increase is most likely due to statistical reasons arising
from the rareness of the event in the small number of included patients.
Stopping, bridging or continuing a medication should always be an individual
decision. In accordance with guidelines from internal medicine for most patients
it will be recommendable to continue with the medication.
PMID- 25132205
TI - Simultaneous determination of phenolic compounds in Equisetum palustre L. by
ultra high performance liquid chromatography with tandem mass spectrometry
combined with matrix solid-phase dispersion extraction.
AB - A method based on matrix solid-phase dispersion extraction followed by ultra high
performance liquid chromatography with tandem mass spectrometry is presented for
the extraction and determination of phenolic compounds in Equisetum palustre.
This method combines the high efficiency of matrix solid-phase dispersion
extraction and the rapidity, sensitivity, and accuracy of ultra high performance
liquid chromatography with tandem mass spectrometry. The influential parameters
of the matrix solid-phase dispersion extraction were investigated and optimized.
The optimized conditions were as follows: silica gel was selected as dispersing
sorbent, the ratio of silica gel to sample was selected to be 2:1 (400/200 mg),
and 8 mL of 80% methanol was used as elution solvent. Furthermore, a fast and
sensitive ultra high performance liquid chromatography with tandem mass
spectrometry method was developed for the determination of nine phenolic
compounds in E. palustre. This method was carried out within <6 min, and
exhibited satisfactory linearity, precision, and recovery. Compared with
ultrasound-assisted extraction, the proposed matrix solid-phase dispersion
procedure possessed higher extraction efficiency, and was more convenient and
time saving with reduced requirements on sample and solvent amounts. All these
results suggest that the developed method represents an excellent alternative for
the extraction and determination of active components in plant matrices.
PMID- 25132207
TI - Use of anion gap in the evaluation of a patient with metabolic acidosis.
AB - High anion gap (AG) metabolic acidosis, a common laboratory abnormality
encountered in clinical practice, frequently is due to accumulation of organic
acids such as lactic acid, keto acids, alcohol metabolites, and reduced kidney
function. The cause of high AG metabolic acidosis often is established easily
using historical and simple laboratory data. Despite this, several challenges in
the diagnosis and management of high AG metabolic acidosis remain, including
quantifying the increase in AG, understanding the relationship between changes in
AG and serum bicarbonate level, and identifying the cause of high AG metabolic
acidosis when common causes are ruled out. The present case was selected to
highlight the importance of the correction of AG for serum albumin level, the use
of actual baseline AG rather than mean normal AG, the relationship between
changes in serum bicarbonate level and AG, and a systematic diagnostic approach
to uncommon causes of high AG metabolic acidosis, such as 5-oxoproline acidosis
(pyroglutamic acidosis).
PMID- 25132208
TI - Biochemical cartilage alteration and unexpected signal recovery in T2* mapping
observed in ankle joints with mobile MRI during a transcontinental multistage
footrace over 4486 km.
AB - OBJECTIVE: The effect of ultra-long distance running on the ankle cartilage with
regard to biochemical changes, thickness and lesions is examined in the progress
of a transcontinental ultramarathon over 4486 km. METHOD: In an observational
field study, repeated follow-up scanning of 22 participants of the TransEurope
FootRace (TEFR) with a 1.5 T MRI mounted on a mobile unit was performed. For
quantitative biochemical and structural evaluation of cartilage a fast low angle
shot (FLASH) T2* weighted gradient-echo (GRE)-, a turbo-inversion-recovery
magnitude (TIRM)- and a fat-saturated proton density (PD)-weighted sequence were
utilized. Statistical analysis of cartilage T2* and thickness changes was
obtained on the 13 finishers (12 male, mean age 45.4 years, BMI 23.5 kg/m2). None
of the nine non-finisher (eight male, mean age 53.8 years, BMI 23.4 kg/m2)
stopped the race due to ankle problems. RESULTS: From a mean of 17.0 ms for
tibial plafond and 18.0 ms for talar dome articular cartilage at baseline, nearly
all observed regions of interest (ROIs) of the ankle joint cartilage showed a
significant T2*-signal increase (25.6% in mean), with standard error ranging from
19% to 33% within the first 2500 km of the ultra-marathon. This initial signal
behavior was followed by a signal decrease. This signal recovery (30.6% of
initial increase) showed a large effect size. No significant morphological or
cartilage thickness changes (at baseline 2.9 mm) were observed. CONCLUSION: After
initial T2*-increase during the first 2000-2500 km, a subsequent T2*-decrease
indicates the ability of the normal cartilage matrix to partially regenerate
under ongoing multistage ultramarathon burden in the ankle joints.
PMID- 25132209
TI - A systematic review of interventions to detect dementia or cognitive impairment.
AB - BACKGROUND: Memory services have been implemented nationally to increase early
dementia diagnosis, and further evaluation of their impact and other strategies
to increase timely dementia diagnosis are needed. AIMS: To systematically review
the literature for interventions intended to increase the detection of dementia
or suspected dementia or people presenting with memory complaints. METHOD: We
searched electronic databases, hand searched references and contacted authors of
included papers, contacted field experts and UK charities and councils for data
about their dementia awareness programmes. RESULTS: We included 13 studies, of
which four were randomised controlled trials (RCT). Two RCTs found that general
practitioner (GP) education increased suspected dementia cases. One RCT found up
to six home visits from a specialist geriatric nurse over 30 months increased the
rate of accurately diagnosed dementia. There was preliminary evidence from non
randomised studies that memory clinics increase timely diagnosis, but no evidence
they increase the overall diagnosis rate. CONCLUSIONS: There is good quality
evidence that GP education increases the number of suspected dementia cases but
not accurate or earlier dementia diagnoses. One RCT reported that multiple visits
from a trained nurse increase the diagnosis rate. There is no cost effectiveness
evidence. Our findings suggest good quality RCTs are needed to test the
effectiveness and cost-effectiveness of interventions to increase dementia
detection.
PMID- 25132206
TI - Randomized controlled pilot study of mindfulness-based stress reduction for
persistently fatigued cancer survivors.
AB - OBJECTIVE: Cancer-related fatigue (CRF) is one of the most common, persistent,
and disabling symptoms associated with cancer and its treatment. Evidence-based
treatments that are acceptable to patients are critically needed. This study
examined the efficacy of mindfulness-based stress reduction (MBSR) for CRF and
related symptoms. METHOD: A sample of 35 cancer survivors with clinically
significant CRF was randomly assigned to a 7-week MBSR-based intervention or wait
list control group. The intervention group received training in mindfulness
meditation, yoga, and self-regulatory responses to stress. Fatigue interference
(primary outcome) and a variety of secondary outcomes (e.g., fatigue severity,
vitality, disability, depression, anxiety, and sleep disturbance) were assessed
at baseline, post-intervention, and 1-month follow-up. Bonferroni correction was
employed to account for multiple comparisons. Controls received the intervention
after the 1-month follow-up. Participants in both groups were followed for 6
months after completing their respective MBSR courses to assess maintenance of
effects. RESULTS: Compared to controls, the MBSR group reported large post
intervention reductions as assessed by effect sizes (d) in the primary outcome,
fatigue interference (d = -1.43, p < 0.001), along with fatigue severity (d =
1.55, p < 0.001), vitality (d = 1.29, p < 0.001), depression (d = -1.30, p <
0.001), and sleep disturbance (d = -0.74, p = 0.001). Results were maintained or
strengthened at 1-month follow-up, the point at which significant improvements in
disability (d = -1.22, p < 0.002) and anxiety (d = -0.98, p = 0.002) occurred.
Improvements in all outcomes were maintained 6 months after completing the
course. MBSR adherence was high, with 90% attendance across groups and high rates
of participant-reported home practice of mindfulness. CONCLUSIONS: Mindfulness
based stress reduction is a promising treatment for CRF and associated symptoms.
PMID- 25132210
TI - Evaluation of the microbial quality of fresh ejaculates of camel (Camelus
dromedarius) semen.
AB - A series of five factorial arranged experiments were conducted to investigate the
effect of different management during semen collection on the microbial quality
(bacterial load, type of microbes and frequency of isolation) of dromedaries'
semen. Microbial analysis of seventy-nine fresh ejaculates from twenty-two camels
showed the presence of nine variant colonies. The most prevalent organisms in the
dromedary semen were species of Staphylococcus, Bacillus and Streptococcus. One
yeast species was represented among the isolates. The middle aged camels (9-13
years) had significantly (P>0.05) higher mean bacterial loads than young (4-8
years) and old aged (14-18 years) animals. The mean bacterial populations of
ejaculates collected by an electro-ejaculator were significantly (P>0.05) higher
than those collected by an artificial vagina. Candida spp. was identified in
53.8% of the samples collected by an electro-ejaculator and was not detected in
ejaculates collected by an artificial vagina. The mean semen bacterial load
detected during the breeding season was significantly (P<0.01) higher than that
collected during the non-breeding season. No fungi were isolated from semen
samples collected in the non-breeding season. The difference between the mean
semen bacterial loads in the first and the second ejaculate was highly
significant (P<0.01). The preputial wash significantly (P<0.01) reduced the
bacterial load. This study revealed that the microbial contamination of
dromedaries' semen is found in different intensities during different management
procedures of semen collection.
PMID- 25132211
TI - Influence of melatonin receptor 1A gene polymorphisms on seasonal reproduction in
Sarda ewes with different body condition scores and ages.
AB - In several species, circadian changes in melatonin concentrations play a key role
in the photoperiodic control of seasonality. In sheep, two silent mutations in
the melatonin receptor 1A gene (MTNR1A) at positions 606 and 612 of the exon II
are associated with seasonal reproduction. However, in some sheep breeds, no
relationships have been found between MTNR1A polymorphisms and reproductive
seasonality. This lack of relationship could be due to effects of breed, body
condition, age, and/or environmental conditions. Thus, the present study was
conducted with the Sarda sheep breed with the aim of documenting the effect of
MTNR1A gene polymorphisms on reproductive resumption and to evaluate whether such
this effect was modified by differences in body condition score (BCS) and age.
Six hundred three- to six-year-old multiparous ewes with BCSs between 2.5 and 3.5
were selected. Genomic DNA was extracted and subjected to PCR to amplify the
ovine exon II of the MTNR1A gene. The amplicons were subjected to digestion with
the restriction enzymes RsaI and MnlI to detect the T606C and A612G
polymorphisms, respectively. Ewes carrying the G/G, G/A, C/C, and C/T genotypes
exhibited higher fertility rates (P<0.05) and fewer numbers of days between the
introduction of rams and parturition (P<0.05) than did the A/A and T/T genotypes.
The data revealed that the MTNR1A gene polymorphisms influenced spring
reproductive resumption in the Sarda sheep breed. Moreover, the data also
indicated that, over the limited ranges evaluated in this study, BCS and age had
no significant influence on reproductive activity.
PMID- 25132213
TI - Li-rich anti-perovskite Li3OCl films with enhanced ionic conductivity.
AB - Anti-perovskite solid electrolyte films were prepared by pulsed laser deposition,
and their room-temperature ionic conductivity can be improved by more than an
order of magnitude in comparison with its bulk counterpart. The cyclability of
Li3OCl films in contact with lithium was evaluated using a Li/Li3OCl/Li symmetric
cell, showing self-stabilization during cycling test.
PMID- 25132212
TI - Durability of the efficacy and safety of alogliptin compared with glipizide in
type 2 diabetes mellitus: a 2-year study.
AB - AIMS: To evaluate the long-term durability of the efficacy of alogliptin compared
with glipizide in combination with metformin in people with type 2 diabetes
inadequately controlled on stable-dose metformin. METHODS: This multicentre,
double-blind, active-controlled study randomized 2639 patients aged 18-80 years
to 104 weeks of treatment with metformin in addition to alogliptin 12.5 mg once
daily (n = 880), alogliptin 25 mg once daily (n = 885) or glipizide 5 mg once
daily, titrated to a maximum of 20 mg (n = 874). The primary endpoint was least
square mean change from baseline in HbA1c level at 104 weeks. RESULTS: The mean
patient age was 55.4 years, the mean diabetes duration was 5.5 years and the mean
baseline HbA1c was 7.6%. HbA1c reductions at week 104 were -0.68%, -0.72% and
0.59% for alogliptin 12.5 and 25 mg and glipizide, respectively [both doses met
the criteria for non-inferiority to glipizide (p<0.001); alogliptin 25 mg met
superiority criteria (p=0.010)]. Fasting plasma glucose concentration decreased
by 0.05 and 0.18 mmol/l for alogliptin 12.5 and 25 mg, respectively, and
increased by 0.30 mmol/l for glipizide (p < 0.001 for both comparisons with
glipizide). Mean weight changes were -0.68, -0.89 and 0.95 kg for alogliptin 12.5
and 25 mg and glipizide, respectively (p < 0.001 for both comparisons with
glipizide). Hypoglycaemia occurred in 23.2% of patients in the glipizide group
vs. 2.5 and 1.4% of patients in the alogliptin 12.5 and 25 mg groups,
respectively. Pancreatitis occurred in one patient in the alogliptin 25 mg group
and three in the glipizide group. CONCLUSIONS: Alogliptin efficacy was sustained
over 2 years in patients with inadequate glycaemic control on metformin alone.
PMID- 25132214
TI - Characterizing genetic variation of adrenergic signalling pathways in Takotsubo
(stress) cardiomyopathy exomes.
AB - AIMS: Exome sequencing was used to genotype comprehensively a Takotsubo (stress)
cardiomyopathy (TC) cohort, enabling investigation of a vast 486 gene network for
adrenergic signalling. METHODS AND RESULTS: Twenty-eight TC subjects, including a
mother-daughter pair and five recurrent cases, underwent whole-exome sequencing.
Frequencies of 17 common, functional adrenergic polymorphisms were statistically
similar to those of population controls. Filtering for rare, predicted
deleterious, catecholamine/adrenergic signalling variants revealed heterozygosity
in 55 genes in TC cases and 59 genes in healthy controls. Overall allele burden
was similar and did not discriminate clinical variables among TC subjects, but
gene identities were largely cohort specific, and TC cases were enriched for
variants within functional domains (68% vs. 48%, P = 0.031). Two-thirds of TC
cases carried more than one filtered adrenergic pathway variant, and 11 genes
harboured a variant in >= 2 cases. The mother-daughter pair shared missense
variants in highly conserved functional domains of ADH5, CACNG1, EPHA4, and
PRKCA. An adrenergic pathway-independent analysis of the cohort exposed no common
gene for TC. CONCLUSIONS: Overall, these data support genetic heterogeneity in TC
susceptibility and a likely polygenic basis, conferring a cumulative effect on
adrenergic pathway dysregulation in a subset of individual subjects. Study of
larger cohorts and non-coding regulatory regions is warranted to define genetic
risk factors for TC further.
PMID- 25132216
TI - How can we improve models of care in inflammatory bowel disease? An international
survey of IBD health professionals.
AB - BACKGROUND AND AIMS: Few studies have specifically examined models of care in
IBD. This survey was designed to help gather information from health
professionals working in IBD services on current care models, and their views on
how to best reshape existing models for IBD care worldwide. METHODS: An online
mixed-methods survey was conducted with health professionals caring for IBD
patients. Recruitment was conducted using the snowballing technique, where
members of professional networks of the investigators were invited to
participate. Results of the survey were summarised using descriptive statistics.
RESULTS: Of the 135 included respondents, 76 (56%) were female, with a median age
of 44 (range: 23-69) years, 50% were GI physicians, 34% nurses, 8% psychologists,
4% dieticians, 2% surgeons, 1% psychiatrists, and 1% physiotherapists. Overall,
73 (54%) respondents considered their IBD service to apply the integrated model
of care, and only 5% reported that they worked exclusively using the biomedical
care (no recognition of psychosocial factors). The majority of respondents
reported including mental health assessment in their standard IBD care (65%), 51%
believed that an ideal IBD service should be managed in specialist led clinics,
and 64% wanted the service to be publicly funded. Respondents pictured an ideal
IBD service as easy-access fully multi-disciplinary, with a significant role for
IBD nurses and routine psychological and nutritional assessment and care.
CONCLUSIONS: Health care professionals believe that an ideal IBD service should:
be fully integrated, involve significant roles of nurses, psychologists and
dieticians, run in specialist clinics, be easily accessible to patients and
publicly funded.
PMID- 25132217
TI - An automated protocol for performance benchmarking a widefield fluorescence
microscope.
AB - Widefield fluorescence microscopy is a highly used tool for visually assessing
biological samples and for quantifying cell responses. Despite its widespread use
in high content analysis and other imaging applications, few published methods
exist for evaluating and benchmarking the analytical performance of a microscope.
Easy-to-use benchmarking methods would facilitate the use of fluorescence imaging
as a quantitative analytical tool in research applications, and would aid the
determination of instrumental method validation for commercial product
development applications. We describe and evaluate an automated method to
characterize a fluorescence imaging system's performance by benchmarking the
detection threshold, saturation, and linear dynamic range to a reference
material. The benchmarking procedure is demonstrated using two different
materials as the reference material, uranyl-ion-doped glass and Schott 475 GG
filter glass. Both are suitable candidate reference materials that are
homogeneously fluorescent and highly photostable, and the Schott 475 GG filter
glass is currently commercially available. In addition to benchmarking the
analytical performance, we also demonstrate that the reference materials provide
for accurate day to day intensity calibration. Published 2014 Wiley Periodicals
Inc.
PMID- 25132218
TI - How mobile health can help tackle the diabetes epidemic and strengthen health
systems: International Diabetes Federation (IDF) response to the public
consultation on the European Commission's Green Paper on mobile health.
PMID- 25132215
TI - Decreased effective connectivity from cortices to the right parahippocampal gyrus
in Alzheimer's disease subjects.
AB - The purpose of this study was to detect effective connectivity (EC) changes in
the default mode network and hippocampus network in 20 patients with Alzheimer's
disease (AD) and 20 cognitively normal (CN) subjects, using multivariate Granger
causality. The authors used the maximum coefficients in the multivariate
autoregression model to quantitatively measure the different EC strength levels
between the CN and AD groups. It was demonstrated that the EC strength difference
can classify AD from CN subjects. Further, the right parahippocampal gyrus
(PHP_R) showed imbalanced bidirectional EC connections. The PHP_R received weaker
input connections from the neocortices, but its output connections were
significantly increased in AD. These findings may provide neural physiological
mechanisms for interpreting AD subjects' memory deficits during the encoding
processes.
PMID- 25132219
TI - Determining the return on investment for evidence-based practice: an essential
skill for all clinicians.
PMID- 25132220
TI - Eye contact modulates cognitive processing differently in children with autism.
AB - In humans, effortful cognitive processing frequently takes place during social
interaction, with eye contact being an important component. This study shows that
the effect of eye contact on memory for nonsocial information is different in
children with typical development than in children with autism, a disorder of
social communication. Direct gaze facilitated memory performance in children with
typical development (n = 25, 6 years old), but no such facilitation was seen in
the clinical group (n = 10, 6 years old). Eye tracking conducted during the
cognitive test revealed strikingly similar patterns of eye movements, indicating
that the results cannot be explained by differences in overt attention.
Collectively, these findings have theoretical significance and practical
implications for testing practices in children.
PMID- 25132222
TI - Evaluation of therapeutic pulmonary surfactants by thin liquid film methods.
AB - An example of the application of the Black Foam Film (BFF) Method and the Wetting
Film Method, using the Microinterferomertric and the Pressure Balance Techniques,
for characterization interfacial properties of the animal derived therapeutic
pulmonary surfactant preparations (TSP), is presented. BFF thickness, probability
of black film formation, and disjoining pressure for foam films from TSP aqueous
solutions are measured as well as the wetting properties of TSP solutions on
solid surfaces with different hydrophobicity have been studied. Interfacial
characteristics such as minimal surfactant concentration to obtain black film
(critical concentration) and concentration at which a black film is 100% obtained
(threshold concentration) are determined. An evaluation of the four widely used
TSP - Curosurf, Infasurf, Survanta, and Alveofact - by these methods has been
carried out. Thus the methods of the thin liquid films are useful tools for
studying the interfacial properties of TSP solutions, as well as for their
improvement.
PMID- 25132221
TI - Hyperfiltration is associated with the development of microalbuminuria in
patients with sickle cell anemia.
PMID- 25132223
TI - Structure of perfluorinated membranes investigated by method of standard contact
porosimetry.
AB - The results of investigation of various factors influencing water distribution in
perfluorinated membrane structure by method of standard contact porosimetry are
summarized. The Nafion membranes (Dupon de Nemoure, USA) and MF-4SK membranes
("Plastpolymer", Russia) were the objects of the research. The influence of
production process and conditioning method on porosimetric curves of
perfluorinated membrane is discussed. New results related to the porosity of
perfluorinated membranes after reinforcing fabric introduction and processing by
organic solvents are reported. The role of the modifying components of various
nature in the shaping of transport channels in perfluorinated membrane is
studied. The influence of polyaniline and hydrogen zirconium phosphate on water
distribution in membrane structure is revealed. The correlation between the
maximum porosity value of the membrane and its diffusion and electroosmotic
permeability, as well as between the fraction of the gel pore volume and membrane
selectivity is established. It allows the prediction of possible changes in the
structural characteristics and also in the transport properties of the membranes
under the influence of the modifying components of different types and various
operating conditions.
PMID- 25132224
TI - Efficacy of thiamethoxam and fipronil, applied alone and in combination, to
control Limonius californicus and Hypnoidus bicolor (Coleoptera: Elateridae).
AB - BACKGROUND: Wireworms, the larval stage of click beetles (family Elateridae), are
significant soil pests of wheat and barley crops in the Pacific Northwest. At
present, few pest management alternatives exist. For several decades, wireworms
were effectively controlled by first-generation insecticides applied to the soil
or as seed treatments. Currently used neonicotinoid insecticides protect crop
seeds and germinating seedlings by temporary toxicity but limited mortality. As a
result, field populations may increase, reaching levels too high for crop
protection. In this study an investigation was made of the combination of two
insecticides to achieve crop protection as well as insect mortality in wheat
fields. RESULTS: Laboratory bioassays using wheat seed treated with fipronil at
1.0 and 5.0 g AI 100 kg(-1) seed resulted in 72-90% mortality of two wireworm
species, Limonius californicus and Hypnoidus bicolor. At a rate of 39 g AI 100
kg(-1) seed, 8 times higher than the high rate of fipronil, thiamethoxam caused
only 10-31% larval mortality in the bioassays, but did protect developing wheat
stands from damage in field trials. Field plots planted with wheat seed treated
with both fipronil (5.0 g AI 100 kg(-1) seed) and thiamethoxam (39.0 g AI 100 kg(
1) seed) had 83% fewer wireworms the following year compared with untreated check
plots. No reduction in population was observed in plots treated with 39.0 g of
thiamethoxam alone. CONCLUSIONS: Fipronil and thiamethoxam can be combined as a
seed treatment to protect wheat crops from wireworm damage and reduce larval
populations in the field.
PMID- 25132226
TI - The role of complexation and competition in the biouptake of europium by a
unicellular alga.
AB - Short-term (60 min) europium (Eu) biouptake fluxes by the freshwater green alga
Chlamydomonas reinhardtii were investigated in the presence and absence of
ligands (e.g., malic acid and citric acid) and a second rare earth metal,
samarium (Sm). Data were interpreted in the context of the biotic ligand model,
which uses experimentally determined stability constants to take into account the
competition and complexation of the metal of interest. In the absence of ligands
or competitors, Eu biouptake was well described by a Michaelis-Menten equation
with the maximal uptake flux (Jmax ) and Michaelis-Menten constant (Km ) of Jmax
= 1.7 * 10(-14) mol cm(-2) s(-1) and Km = 10(-7.0) M (corresponding to an
affinity constant of 10(7.0) M(-1) ). Biouptake of Eu (or Sm) decreased as the
concentration of a competing rare earth element (i.e., Sm or Eu) increased, as
predicted by the biotic ligand model. On the other hand, when hydrophilic
complexes were formed with citric and malic acid, Eu biouptake was much greater
than predicted on the basis of free ion concentrations alone. Overall, the
results showed that for C. reinhardtii the rare earth elements were likely to
share a common biouptake pathway; biouptake of one rare earth element was reduced
when another was present, and rare earth element complexes were bioavailable.
PMID- 25132225
TI - Nd: YAG laser posterior capsulotomy rates in myopic eyes after implantation of
capsular tension ring.
AB - BACKGROUND: The aim f this study was to evaluate the effect of capsular tension
ring implantation during cataract surgery on the incidence of neodymium: YAG (Nd:
YAG) laser posterior capsulotomy in myopic (axial length [AL] >=25.00 mm) eyes.
MATERIAL/METHODS In this retrospective study, the records of the cases of 117
myopic patients who underwent cataract surgery between January 2004 and January
2011 were reviewed. A total of 153 eyes with an axial length of 25 mm or higher
were included in the study with consideration of exclusion criteria mentioned
below. Eyes were grouped by presence or lack of capsular tension ring (CTR+ and
CTR-, respectively). RESULTS: The study included 153 eyes from 107 myopic
patients. Hydrophilic acrylic IOL and capsular tension ring (CTR) were implanted
in 78 eyes (CTR+ group), and 75 eyes received only the hydrophilic acrylic IOL
(CTR- group). Six eyes (7.6%) in CTR+ and 16 eyes (21.3%) in CTR- required Nd:
YAG laser capsulotomy within 7 years. The difference between the 2 groups was
statistically significant (p=0.021). CONCLUSIONS: Because CTRs significantly
decrease subsequent need for Nd: YAG laser posterior capsulotomy in myopic
patients, are very inexpensive, and provide other benefits, our data suggest that
the use of CTRs in myopic eyes undergoing cataract surgery with an hydrophilic
acrylic IOL implantation is advantageous and should be standard practice.
PMID- 25132227
TI - Birth preparedness and complication readiness among women of child bearing age
group in Goba woreda, Oromia region, Ethiopia.
AB - BACKGROUND: Birth preparedness and complication readiness is the process of
planning for normal birth and anticipating the actions needed in case of an
emergency. It is also a strategy to promote the timely use of skilled maternal
care, especially during childbirth, based on the theory that preparing for
childbirth reduces delays in obtaining this care. Therefore, the aim of this
study was to assess birth preparedness and complication readiness among women of
child bearing age group in Goba woreda, Oromia region, Ethiopia. METHODS: A
community based cross sectional study was conducted in Goba woreda, Oromia
region, Ethiopia. Multistage sampling was employed. Descriptive, binary and
multiple logistic regression analyses were conducted. Statistically significant
tests were declared at a level of significance of P value < 0.05. RESULTS: Only
29.9% of the respondents were prepared for birth and its complications. And, only
82 (14.6%) study participants were knowledgeable about birth preparedness and
complication readiness.Variables having statistically significant association
with birth preparedness and complication readiness of women were attending up to
primary education (AOR = 3.24, 95% CI = 1.75, 6.02), attending up to secondary
and higher level of education (AOR = 2.88, 95% CI = 1.34, 6.15), the presence of
antenatal care follow up (AOR = 8.07, 95% CI = 2.41,27.00), knowledge about key
danger signs during pregnancy (AOR = 1.74, 95% CI = 1.06,2.88), and knowledge
about key danger signs during the postpartum period (AOR = 2.08, 95% CI =
1.20,3.60). CONCLUSIONS: Only a small number of respondents were prepared for
birth and its complications. Furthermore, the vast majority of women were not
knowledgeable about birth preparedness and complication readiness. Residence,
educational status, ANC follow up, knowledge of key danger signs during pregnancy
and the postpartum period were independent predictors of birth preparedness and
complication readiness.
PMID- 25132228
TI - Plasticity of vulnerability to leaf hydraulic dysfunction during acclimation to
drought in grapevines: an osmotic-mediated process.
AB - Previous studies have reported correlation of leaf hydraulic vulnerability with
pressure-volume parameters related to cell turgor. This link has been explained
on the basis of the effects of turgor on connectivity among cells and tissue
structural integrity, which affect leaf water transport. In this study, we tested
the hypothesis that osmotic adjustment to water stress would shift the leaf
vulnerability curve toward more negative water potential (Psi leaf ) by
increasing turgor at low Psi leaf . We measured leaf hydraulic conductance (K
leaf ), K leaf vulnerability [50 and 80% loss of K leaf (P50 and P80 ); |Psi leaf
| at 50 and 80% loss of K leaf , respectively), bulk leaf water relations, leaf
gas exchange and sap flow in two Vitis vinifera cultivars (Tempranillo and
Grenache), under two water treatments. We found that P50 , P80 and maximum K leaf
decreased seasonally by more than 20% in both cultivars and watering treatments.
However, K leaf at 2 MPa increased threefold, while osmotic potential at full
turgor and turgor loss point decreased. Our results indicate that leaf resistance
to hydraulic dysfunction is seasonally plastic, and this plasticity may be
mediated by osmotic adjustment.
PMID- 25132229
TI - Excessive microglial activation aggravates olfactory dysfunction by impeding the
survival of newborn neurons in the olfactory bulb of Niemann-Pick disease type C1
mice.
AB - Progressive olfactory impairment is one of the earliest markers of
neurodegeneration. However, the underlying mechanism for this dysfunction remains
unclear. The present study investigated the possible role of microgliosis in
olfactory deficits using a mouse model of Niemann-Pick disease type C1 (NPC1),
which is an incurable neurodegenerative disorder with disrupted lipid
trafficking. At 7weeks of age, NPC1 mutants showed a distinct olfactory
impairment in an olfactory test compared with age-matched wild-type controls
(WT). The marked loss of olfactory sensory neurons within the NPC1 affected
olfactory bulb (NPC1-OB) suggests that NPC1 dysfunction impairs olfactory
structure. Furthermore, the pool of neuroblasts in the OB was diminished in NPC1
mice despite the intact proliferative capacity of neural stem/progenitor cells in
the subventricular zone. Instead, pro-inflammatory proliferating microglia
accumulated extensively in the NPC1-OB as the disease progressed. To evaluate the
impact of abnormal microglial activation on olfaction in NPC1 mice, a microglial
inhibition study was performed using the anti-inflammatory agent Cyclosporin A
(CsA). Importantly, long-term CsA treatment in NPC1 mice reduced reactive
microgliosis, restored the survival of newly generated neurons in the OB and
improved overall performance on the olfactory test. Therefore, our study
highlights the possible role of microglia in the regulation of neuronal turnover
in the OB and provides insight into the possible therapeutic applications of
microglial inhibition in the attenuation or reversal of olfactory impairment.
PMID- 25132230
TI - Central type primitive neuroectodermal tumor/neuroblastoma of the uterus: a case
report.
AB - We encountered a 63-year-old woman who had a uterine tumor with peritoneal
dissemination and para-aortic lymph node metastasis. Microscopic specimens of the
tumor showed a small blue round-cell tumor. Immunohistochemistry showed cells to
be negative for cytokeratin AE1/3, desmin, myogenin, CD10, CD34, and CD99, focal
positive for vimentin, and positive for muscle-specific actin (HHF-35),
neurofilament, synaptophysin and CD56. Fluorescence in situ hybridization
revealed no split signal showing Ewing sarcoma breakpoint region 1 gene
translocation. Deletion of 1p36 was identified in 30% of the tumor cells. These
findings are thought to be equivalent to central type primitive neuroectodermal
tumors/neuroblastoma. Cytoreductive debulking surgery followed by chemotherapy,
including cyclophosphamide, vincristine and adriamycin, resulted in complete
remission. She has no evidence of disease at 24 months after surgery.
PMID- 25132231
TI - Microbial weeds in hypersaline habitats: the enigma of the weed-like Haloferax
mediterranei.
AB - Heterotrophic prokaryotic communities that inhabit saltern crystallizer ponds are
typically dominated by two species, the archaeon Haloquadratum walsbyi and the
bacterium Salinibacter ruber, regardless of location. These organisms behave as
'microbial weeds' as defined by Cray et al. (Microb Biotechnol 6: 453-492, 2013)
that possess the biological traits required to dominate the microbiology of these
open habitats. Here, we discuss the enigma of the less abundant Haloferax
mediterranei, an archaeon that grows faster than any other, comparable extreme
halophile. It has a wide window for salt tolerance, can grow on simple as well as
on complex substrates and degrade polymeric substances, has different modes of
anaerobic growth, can accumulate storage polymers, produces gas vesicles, and
excretes halocins capable of killing other Archaea. Therefore, Hfx. mediterranei
is apparently more qualified as a 'microbial weed' than Haloquadratum and
Salinibacter. However, the former differs because it produces carotenoid pigments
only in the lower salinity range and lacks energy-generating retinal-based, light
driven ion pumps such as bacteriorhodopsin and halorhodopsin. We discuss these
observations in relation to microbial weed biology in, and the open-habitat
ecology of, hypersaline systems.
PMID- 25132232
TI - Physiatry practice now and in 2032: how to thrive in the post-health care reform
world.
AB - Health care reform is upon us, including changes in models of care delivery and
physician and institution compensation. The resulting tsunami of uncertainty
offers physiatrists the opportunity to relocate to higher ground and help the
specialty thrive as well as to identify the possible quagmires into which
practices could sink. For this reason, it is prudent for physiatrists to more
carefully consider how their professional lives may be altered in the aftermath
of reform. We believe that understanding and preparation will facilitate
opportunities and mitigate challenges. In this essay, we will discuss various
alternative scenarios that represent population health and health care delivery
in the year 2032, the real-world opportunities and challenges for the physiatrist
in the present and in the next 2 decades, along with ideas as to how physiatry
can thrive in the post-health care reform world.
PMID- 25132233
TI - Comparison of diagnostic accuracy of aspartate aminotransferase to platelet ratio
index and fibrosis-4 index for detecting liver fibrosis in adult patients with
chronic hepatitis B virus infection: a systemic review and meta-analysis.
AB - The aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index
based on the four factors (Fibrosis 4 index; FIB-4) are the two most widely
studied noninvasive tools for assessing liver fibrosis. Our aims were to
systematically review the performance of APRI and FIB-4 in hepatitis B virus
(HBV) infection in adult patients and compare their advantages and disadvantages.
We examined the diagnostic accuracy of APRI and FIB-4 for significant fibrosis,
advanced fibrosis, and cirrhosis based on their sensitivity, specificity,
positive predictive value, negative predictive value, and area under the receiver
operating characteristic curve (AUROC). Heterogeneity was explored using
metaregression. Our systemic review and meta-analysis included 16 articles of
APRI only, 21 articles of APRI and FIB-4 and two articles of FIB-4 for detecting
different levels of liver fibrosis. With an APRI threshold of 0.5, 1.0, and 1.5,
the sensitivity and specificity values were 70.0% and 60.0%, 50.0% and 83.0%, and
36.9% and 92.5% for significant fibrosis, advanced fibrosis, and cirrhosis,
respectively. With an FIB-4 threshold of 1.45 and 3.25, the sensitivity and
specificity values were 65.4% and 73.6% and 16.2% and 95.2% for significant
fibrosis. The summary AUROC values using APRI and FIB-4 for the diagnosis of
significant fibrosis, advanced fibrosis, and cirrhosis were 0.7407 (95%
confidence interval [CI]: 0.7033-0.7781) and 0.7844 (95% CI: 0.7450-0.8238; (Z =
1.59, P = 0.06), 0.7347 (95% CI: 0.6790-0.7904) and 0.8165 (95% CI: 0.7707
0.8623; Z = 2.01, P = 0.02), and 0.7268 (95% CI: 0.6578-0.7958) and 0.8448 (95%
CI: 0.7742-0.9154; (Z = 2.34, P = 0.01), respectively. CONCLUSIONS: Our meta
analysis suggests that APRI and FIB-4 can identify hepatitis B-related fibrosis
with a moderate sensitivity and accuracy.
PMID- 25132234
TI - Same but different: tuberculosis treatment and care among migrants from different
countries of origin in Israel.
AB - INTRODUCTION: Israel hosts documented labor migrants (DLM), and recently also
undocumented migrants (UDM), mostly from Horn of Africa. This study aims to
compare treatment outcomes and other clinical aspects between a sample of 154 DLM
and 113 UDM who were treated in two tuberculosis clinics between 2005 and 2010.
RESULTS AND DISCUSSION: Compared to DLM, UDM were younger males, stayed in Israel
for shorter periods, had lower coverage of medical insurance, were less likely to
be employed, and had greater difficulties in communication with the medical
staff. UDM were more likely to demonstrate tuberculosis-related symptoms than
DLM, were more commonly diagnosed with pulmonary TB, and had shorter patient and
system delays and their treatment success rate was better than DLM, who were more
likely to be transferred out. CONCLUSION: UDM achieved better treatment outcomes,
as they were screened upon entry and treatment was initiated in detention, while
DLM were diagnosed in the community and may have felt more secure to abandon
treatment.
PMID- 25132235
TI - Does preconception care work?
AB - BACKGROUND: To date, there is a lack of evidence to suggest that a systematic and
coordinated approach to prepregnancy care might make a difference. AIMS: To
evaluate whether women who receive preconception care through a structured
approach will be more likely to be healthy around the time of conception compared
with women who plan their pregnancy but have not been exposed to preconception
care. METHODS: A case control study was undertaken of women who attended the
preconception care service and subsequently conceived, received maternity care
and gave birth at Mater Health Services Brisbane between January 2010 and January
2013. Pregnancy information and birth outcomes for each woman who attended the
service were matched with those of three women who reported that they had planned
their pregnancy but did not attend the service. Records were matched for
prepregnancy BMI, age, parity, prepregnancy smoking status and number of health
conditions. RESULTS: Pregnant women who attended preconception care were more
likely to have received adequate peri-conceptual folate, to report being
vaccinated against influenza and hepatitis B, to have consulted with a specialist
with the specific aim of optimising a pre-existing health condition and to report
less weight gain up until booking. Preterm birth and hypertensive disorders of
pregnancy were less common amongst women who had attended preconception care, and
there were trends towards a decreased incidence of gestational diabetes, LGA and
fetal anomalies. CONCLUSION: These preliminary data provide some optimism that a
comprehensive preconception care service may positively influence maternal and
neonatal outcomes.
PMID- 25132236
TI - Cowden syndrome: recognizing and managing a not-so-rare hereditary cancer
syndrome.
AB - Cowden syndrome (CS) is an autosomal dominant hereditary cancer syndrome causing
increased risk for breast, thyroid, renal, uterine, and other cancers as well as
benign neoplasias and neurodevelopmental concerns. Timely diagnosis of affected
patients is key, as early recognition allows for high-risk screening and other
preventative measures prior to a patient enduring multiple cancer diagnoses. This
review will highlight the cardinal features of CS and management recommendations
for affected patients.
PMID- 25132237
TI - Genome-wide analysis reveals artificial selection on coat colour and reproductive
traits in Chinese domestic pigs.
AB - Pigs from Asia and Europe were independently domesticated from c. 9000 years ago.
During this period, strong artificial selection has led to dramatic phenotypic
changes in domestic pigs. However, the genetic basis underlying these
morphological and behavioural adaptations is relatively unknown, particularly for
indigenous Chinese pigs. Here, we performed a genome-wide analysis to screen 196
regions with selective sweep signals in Tongcheng pigs, which are a typical
indigenous Chinese breed. Genes located in these regions have been found to be
involved in lipid metabolism, melanocyte differentiation, neural development and
other biological processes, which coincide with the evolutionary phenotypic
changes in this breed. A synonymous substitution, c.669T>C, in ESR1, which
colocalizes with a major quantitative trait locus for litter size, shows extreme
differences in allele frequency between Tongcheng pigs and wild boars. Notably,
the variant C allele in this locus exhibits high allele frequency in most Chinese
populations, suggesting a consequence of positive selection. Five genes (PRM1,
PRM2, TNP2, GPR149 and JMJD1C) related to reproductive traits were found to have
high haplotype similarity in Chinese breeds. Two selected genes, MITF and EDNRB,
are implied to shape the two-end black colour trait in Tongcheng pig. Subsequent
SNP microarray studies of five Chinese white-spotted breeds displayed a
concordant signature at both loci, suggesting that these two genes are
responsible for colour variations in Chinese breeds. Utilizing massively parallel
sequencing, we characterized the candidate sites that adapt to artificial and
environmental selections during the Chinese pig domestication. This study
provides fundamental proof for further research on the evolutionary adaptation of
Chinese pigs.
PMID- 25132238
TI - The cistrome and gene signature of androgen receptor splice variants in
castration resistant prostate cancer cells.
AB - PURPOSE: Spliced variant forms of androgen receptor were recently identified in
castration resistant prostate cancer cell lines and clinical samples. We
identified the cistrome and gene signature of androgen receptor splice variants
in castration resistant prostate cancer cell lines and determined the clinical
significance of androgen receptor splice variant regulated genes. MATERIALS AND
METHODS: The castration resistant prostate cancer cell line 22Rv1, which
expresses full-length androgen receptor and androgen receptor splice variants
endogenously, was used as the research model. We established 22Rv1-ARFL(-)/ARV(+)
and 22Rv1-ARFL(-)/ARV(-) through RNA interference. Chromatin immunoprecipitation
coupled with next generation sequencing and microarray techniques were used to
identify the cistrome and gene expression profiles of androgen receptor splice
variants in the absence of androgen. RESULTS: Androgen receptor splice variant
binding sites were identified in 22Rv1-ARFL(-)/ARV(+). A gene set was regulated
uniquely by androgen receptor splice variants but not by full-length androgen
receptor in the absence of androgen. Integrated analysis revealed that some genes
were directly modulated by androgen receptor splice variants. Unsupervised
clustering analysis showed that the androgen receptor splice variant gene
signature differentiated benign from malignant prostate tissue as well as
localized prostate cancer from metastatic castration resistant prostate cancer
specimens. Some genes that were modulated uniquely by androgen receptor splice
variants also correlated with histological grade and biochemical failure.
CONCLUSIONS: Androgen receptor splice variants can bind to DNA independent of
full-length androgen receptor in the absence of androgen and modulate a unique
set of genes that is not regulated by full-length androgen receptor. The androgen
receptor splice variant gene signature correlates with disease progression. It
distinguishes primary cancer from castration resistant prostate cancer specimens
and benign from malignant prostate specimens.
PMID- 25132240
TI - Single fraction radiosurgery for the treatment of renal tumors.
AB - PURPOSE: High dose local stereotactic radiosurgery was performed in select
patients to improve local tumor control and overall survival. We report on
patients with renal tumors treated with single fraction robotic stereotactic
radiosurgery. MATERIALS AND METHODS: A total of 40 patients with a median age of
64 years who had an indication for nephrectomy and subsequent hemodialysis were
entered in a prospective case-control study of single fraction stereotactic
radiosurgery. Of the patients 11 had transitional cell cancer and 29 had renal
cell cancer. Tumor response, renal function, survival and adverse events were
estimated every 3 months. Followup was at least 6 months. RESULTS: A total of 45
renal tumors were treated. Median followup was 28.1 months (range 6.0 to 78.3).
The local tumor control rate 9 months after stereotactic radiosurgery was 98%
(95% CI 89-99). There was a measurable size reduction in 38 lesions, including
complete remission in 19. Renal function remained stable. Using the CKD-EPI
(Chronic Kidney Disease Epidemiology Collaboration) equation median creatinine
clearance was 76.8 (range 25.3 to 126.3) and 70.3 ml/minute/1.73 m(2) (range 18.6
to 127.3) at baseline and followup, respectively (p = 0.89). Grade I
erythrodermia developed in 1 patient, 3 reported grade I fatigue and 2 reported
grade I nausea. Nephrectomy was avoided in all cases. CONCLUSIONS: Single
fraction stereotactic radiosurgery as an outpatient procedure is a treatment
modality with short-term safety and efficacy. It avoids treatment related loss of
renal function and hemodialysis in select patients with transitional or renal
cell cancer. At short followup oncologic results were similar to those of other
ablative techniques for renal tumors. To date functional results have been
excellent. Further studies are needed to determine the long-term results and
limits of stereotactic radiosurgery in this setting.
PMID- 25132239
TI - Increased brain gray matter in the primary somatosensory cortex is associated
with increased pain and mood disturbance in patients with interstitial
cystitis/painful bladder syndrome.
AB - PURPOSE: Interstitial cystitis is a highly prevalent pain condition estimated to
affect 3% to 6% of women in the United States. Emerging data suggest there are
central neurobiological components to the etiology of this disease. We report the
first brain structural imaging findings from the MAPP network with data on more
than 300 participants. MATERIALS AND METHODS: We used voxel based morphometry to
determine whether human patients with chronic interstitial cystitis display
changes in brain morphology compared to healthy controls. A total of 33 female
patients with interstitial cystitis without comorbidities and 33 age and gender
matched controls taken from the larger sample underwent structural magnetic
resonance imaging at 5 MAPP sites across the United States. RESULTS: Compared to
controls, females with interstitial cystitis displayed significant increased gray
matter volume in several regions of the brain including the right primary
somatosensory cortex, the superior parietal lobule bilaterally and the right
supplementary motor area. Gray matter volume in the right primary somatosensory
cortex was associated with greater pain, mood (anxiety) and urological symptoms.
We explored these correlations in a linear regression model, and found
independent effects of these 3 measures on primary somatosensory cortex gray
matter volume, namely clinical pain (McGill pain sensory total), a measure of
urgency and anxiety (HADS). CONCLUSIONS: These data support the notion that
changes in somatosensory gray matter may have an important role in pain
sensitivity as well as affective and sensory aspects of interstitial cystitis.
Further studies are needed to confirm the generalizability of these findings to
other pain conditions.
PMID- 25132242
TI - Evaluation of outcome and prognostic factors in extraosseous Ewing sarcoma.
AB - BACKGROUND: Data on extraosseous Ewing sarcoma (EES) with uniform chemotherapy
protocol are minimal. We aimed to examine this aspect in our patients, identify
prognostic factors and compare the same with osseous Ewing sarcoma. PROCEDURES: A
single institutional data review of patients with EES treated between June 2003
and November 2011 with uniform chemotherapy and evaluated on intent-to-treat
analysis was done. RESULTS: Of 374 patients with Ewing sarcoma, 60 (16%) were EES
with median age 16 years; 20 (33%) had metastases. After median follow-up of 25
months (range: 1.7-104.4), 5-year event free survival (EFS), OS, and local
control-rate were 47.1 +/- 7.9%, 61.6 +/- 7.8%, and 77.9 +/- 8.6%, respectively
for entire EES cohort. In multivariate analysis, hemoglobin <= 10 g/dl (P =
0.03), and white blood cell count (WBC) >11 * 10(9) /L (P = 0.009) predicted
inferior EFS for the entire EES cohort. Low hemoglobin (P = 0.05) and high LDH (P
= 0.01) predicted inferior OS for the entire EES cohort on multivariate analysis.
As compared to the cohort of skeletal primary (n = 314), higher proportion of
patients underwent surgery in the cohort of EES (P = .003); EFS (P = 0.004) and
OS (P = 0.08) were superior for patients with EES than patients with skeletal
Ewing sarcoma. CONCLUSION: These data of EES suggests that low hemoglobin and
high WBC count adversely affect EFS. Overall outcome was significantly better for
EES than skeletal primary tumors.
PMID- 25132241
TI - A role for PERK in the mechanism underlying fluoride-induced bone turnover.
AB - While it has been well-documented that excessive fluoride exposure caused the
skeletal disease and osteoblasts played a critical role in the advanced skeletal
fluorosis, the underlying mechanism that mediated these effects remain poorly
understood. The present study was undertaken to examine the effect of fluoride on
bone of rats and MC3T3-E1 cells in vitro. Herein we found pathological features
of high bone turnover in fluoride-treated rats, which was supported by an
increase of osteogenic and osteoclastogenic genes expression in different stages
of fluoride exposure. The skeletal toxicity of fluoride was accompanied by
activation of endoplasmic reticulum (ER) stress and subsequent unfolded protein
response (UPR). A novel finding of this study was that expression of PKR-like
endoplasmic reticulum kinase (PERK) was the same trend with receptor activator
for nuclear factor-kappa B ligand (RANKL), and NF-E2 p45-related factor 2 (Nrf2)
was the same trend with Runt-related transcription factor 2 (Runx2) in bones of
rats exposed to varied fluoride condition. Based on these data, we hypothesized
that up-regulation of PERK probably played a role in mediating bone turnover
induced by fluoride. Action of fluoride on MC3T3-E1 cells differentiation was
demonstrated through analysis of alkaline phosphatase (ALP) activity and
mineralized nodules formation. Meantime, an increase of binding immunoglobulin
protein (BiP) expression indicated the active ER stress in cells exposed to
various dose of fluoride. Blocking PERK expression using siRNA showed the obvious
decrease of osteogenic and osteoclastogenic factors expression in MC3T3-E1 cells
exposed to certain dose of fluoride that could positively stimulate osteoblastic
viability. In conclusion these findings underscore the importance of PERK in
modulating fluoride induced bone formation and bone resorption. Understanding the
link between PERK and bone turnover could probe into the mechanism underlying
different bone lesion of skeletal fluorosis.
PMID- 25132244
TI - Keeping up with the Cadillacs: What Health Insurance Disparities, Moral Hazard,
and the Cadillac Tax Mean to The Patient Protection and Affordable Care Act.
AB - A major goal of The Patient Protection and Affordable Care Act is to broaden
health care access through the extension of insurance coverage. However, little
attention has been given to growing disparities in access to health care among
the insured, as trends to reduce benefits and increase cost sharing (deductibles,
co-pays) reduce affordability and access. Through a political economic
perspective that critiques moral hazard, this article draws from ethnographic
research with the United Steelworkers (USW) at a steel mill and the Retail,
Wholesale and Department Store Union (RWDSU) at a food-processing plant in urban
Central Appalachia. In so doing, this article describes difficulties of health
care affordability on the eve of reform for differentially insured working
families with employer-sponsored health insurance. Additionally, this article
argues that the proposed Cadillac tax on high-cost health plans will increase
problems with appropriate health care access and medical financial burden for
many families.
PMID- 25132243
TI - Natural calamities and 'the Big Migration': challenges to the Mongolian health
system in 'the Age of the Market'.
AB - Beginning with the demise of the socialist state system in 1990, Mongolia
embarked on a process of neoliberal economic reform, initiating what is known
among the Mongols as 'the Age of the Market'. The socialist health system has
been replaced by a series of reforms initiated and substantiated by foreign donor
organisations. This paper critically examines Mongolia's health system and
discusses the extent to which this 'system', despite its provision of universal,
accessible and essential primary health care services, is unable to accommodate
the health needs of poor urban in-migrants and nomadic herders in remote
provinces. With a particular focus on recurrent natural winter disasters (dzud)
and an escalating rural to urban migration, the paper argues that the issues of
access to health services and health system strengthening must be understood in
relation to factors external to the health system. Ethnographic research
highlights that despite a growing economy, considerable external aid and an
established primary health care model, weak rural politics, environmental
challenges and economic constraints create escalating health vulnerability among
the poorest in Mongolia.
PMID- 25132245
TI - What is the optimal treatment for presbyphonia?
PMID- 25132246
TI - Reply: can implanted venous access ports remain patent without maintenance flush
lock?
PMID- 25132247
TI - Does dexmedetomidine have a cardiac protective effect during non-cardiac surgery?
A randomised controlled trial.
AB - This study was designed to determine the effects of dexmedetomidine on
perioperative myocardial injury by observing peripheral circulatory changes in
response to tracheal intubation and extubation, myocardial enzyme levels,
myocardial ischaemia improvements, cardiovascular adverse events and cytokines in
patients with coronary heart disease (CHD) undergoing non-cardiac surgery. This
study was a prospective, randomized, double-blind trial. Eighty patients having
CHD were scheduled for elective hip-replacement surgery and randomly allocated to
receive a loading dose of 1 MUg/kg dexmedetomidine followed by a 0.2 MUg/kg per h
infusion (Dex group; n = 40) or normal saline (control group; n = 40). Systolic
blood pressure, diastolic blood pressure, mean arterial pressure, heart rate,
rate-pressure product and changes in ST-T segment on the electrocardiogram were
recorded every 5 min during surgery. Serum creatine kinase-MB (CK-MB), cardiac
troponin I (cTnI), glycogen phosphorylase BB (GP-BB), interleukin (IL)-6 and
tumour necrosis factor (TNF)-alpha protein levels were determined preoperatively,
at the end of surgery and 12 and 24 h after surgery. The improvement rate of
myocardial ischaemia was higher in the Dex than control group (87.5% vs 32.5%,
respectively; P < 0.05). In addition, the Dex group had lower serum CK-MB, IL-6,
cTnI and GP-BB concentrations than the control group (P < 0.05). There was no
significance difference in TNF-alpha between the two groups (P > 0.05).
Dexmedetomidine can reduce myocardial injury and cytokine levels in patients with
CHD undergoing non-cardiac surgery.
PMID- 25132249
TI - Considerations in understanding the ocular surface microbiome.
PMID- 25132250
TI - Choroidal changes associated with bruch membrane pathology in pseudoxanthoma
elasticum.
PMID- 25132248
TI - Association of interleukin-8 and neutrophils with nasal symptom severity during
acute respiratory infection.
AB - Using a large data set (n = 811), the relationship between acute respiratory
infection illness severity and inflammatory biomarkers was investigated to
determine whether certain symptoms are correlated more closely than others with
the inflammatory biomarkers, interleukin-8 (IL-8) and nasal neutrophils.
Participants with community acquired acute respiratory infection underwent nasal
lavage for IL-8 and neutrophil testing, in addition to multiplex polymerase chain
reaction (PCR) methods for the detection and identification of respiratory
viruses. Information about symptoms was obtained throughout the duration of the
illness episode using the well-validated Wisconsin Upper Respiratory Symptom
Survey (WURSS-21). Global symptom severity was calculated by the area under the
curve (AUC) plotting duration versus WURSS total. Of the specimens tested, 56%
were positively identified for one or more of nine different respiratory viruses.
During acute respiratory infection illness, both IL-8 and neutrophils positively
correlate with AUC (r(s) = 0.082, P = 0.022; r(s) = 0.080, P = 0.030). IL-8 and
neutrophils correlate with nasal symptom severity: runny nose (r = 0.13, P = <
0.00001; r = 0.18, P = < 0.003), plugged nose (r = 0.045, P = 0.003; r = 0.14, P
= 0.058), and sneezing (r = -0.02, P = < 0.0001; r = -0.0055, P = 0.31).
Neutrophils correlate with some quality of life measures such as sleeping well (r
= 0.15, P = 0.026). Thus, the study demonstrates that IL-8 and neutrophils are
correlated with severity of nasal symptoms during acute respiratory infection.
Further research is necessary to determine if the concentration of these or other
biomarkers can predict the overall duration and severity of acute respiratory
infection illness.
PMID- 25132251
TI - Importance of birth weight as a risk factor for severe retinopathy of prematurity
when gestational age is 30 or more weeks.
PMID- 25132252
TI - Reply: To PMID 24727260.
PMID- 25132253
TI - Clinical manifestations of patients with intraocular inflammation and positive
QuantiFERON-TB gold in-tube test in a country nonendemic for tuberculosis.
PMID- 25132254
TI - Reply: To PMID 24582994.
PMID- 25132255
TI - Pancreatic surgical biopsy in 24 dogs and 19 cats: postoperative complications
and clinical relevance of histological findings.
AB - OBJECTIVE: To assess the immediate postoperative complications associated with
pancreatic biopsy in dogs and cats and review the clinical relevance of biopsy
findings. METHODS: Retrospective review of clinical records from two referral
institutions for cases undergoing pancreatic biopsy between 2000 and 2013.
RESULTS: Twenty-four dogs and 19 cats that had surgical pancreatic biopsy had
sufficient detail in their clinical records and fulfilled the inclusion criteria.
Postoperative complications were seen in 10 cases of which 5 were suggestive of
post-surgical pancreatitis. Two patients were euthanased within 10 days of
surgery because of the underlying disease; neither suffered postoperative
complications. Pancreatic pathology was found in 19 cases, 7 cases showed no
change other than benign pancreatic nodular hyperplasia, and no abnormalities
were seen in 18 cases. CLINICAL SIGNIFICANCE: Complications may be encountered
following surgical pancreatic biopsy, although the risk should be minimal with
good surgical technique. Pancreatic biopsy may provide a useful contribution to
case management but it is not clear whether a negative pancreatic biopsy should
be used to rule out pancreatic disease. Dogs were more likely to have no
significant pathology found on pancreatic biopsy than cats, where chronic
pancreatitis was the most common finding.
PMID- 25132256
TI - Effect of Astragalus polysaccharides on expression of TNF-alpha, IL-1beta and
NFATc4 in a rat model of experimental colitis.
AB - AIM: Astragalus membranaceus is a Chinese medicinal herb and has been shown to
improve hapten-induced experimental colitis. One of its major components is
polysaccharides. We investigated the effect of Astragalus polysaccharides (APS)
on expression of TNF-alpha, IL-1beta and NFATc4 in a rat model of experimental
colitis. METHODS: The experimental colitis model was induced by TNBS. Forty five
rats were divided into five groups (n=9): Normal control group, receiving ethanol
vehicle with no TNBS during induction and IP saline injection during treatment;
TNBS colitis model group (TNBS+IP saline), receiving only IP saline vehicle
treatment; APS low dose group (TNBS+L-APS), receiving APS 100mg/kg; APS high dose
group (TNBS+H-APS), receiving APS 200mg/kg; and positive control group
(TNBS+Dexm), receiving dexamethasone 0.3mg/kg. The clinical features, macroscopic
and microscopic scores were assessed. The expressions of TNF-alpha, IL-1beta and
NFATc4 were measured by real-time PCR and ELISA assays. RESULTS: Compared to
normal control rats, TNBS+IP saline had significant weight loss, increased
macroscopic and microscopic scores, higher disease activity index (DAI) up
regulation of TNF-alpha, IL-1beta and NFATc4 mRNA expression and up-regulation of
TNF-alpha and IL-1beta protein expression. Compared to TNBS+IP saline, treatment
with APS or dexamethasone significantly reduced DAI, partially but significantly
prevented TNBS colitis-induced weight loss and improved both macroscopic and
microscopic scores; high dose APS or dexamethasone significantly down-regulated
TNF-alpha and IL-1beta expressions (both mRNA and protein) and up-regulated
NFATc4 mRNA and protein expression. The effect of high dose APS and dexamethasone
is comparable. CONCLUSIONS: APS significantly improved experimental TNBS-induced
colitis in rats through regulation of TNF-alpha, IL-1beta and NFATc4 expression.
PMID- 25132257
TI - Biomechanical comparison of a locking compression plate combined with an
intramedullary pin or a polyetheretherketone rod in a cadaveric canine tibia gap
model.
AB - OBJECTIVE: To compare the biomechanical properties of a 10-hole 3.5 mm locking
compression plate (LCP) with 2 proximal and 2 distal bicortical locked screws
reinforced with either a Steinmann pin of 30-40% the medullary diameter or a poly
ether-ether-ketone (PEEK) rod of ~75% the medullary diameter in a cadaveric tibia
gap model. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Cadaveric canine
tibias (n = 8 pair). METHODS: Each construct had a 10-hole 3.5 mm LCP with 2
screws per fracture fragment using a comminuted tibia gap model. The Steinmann
pin constructs had a 2.4 mm intramedullary pin whereas the PEEK-rod constructs
had a 6 mm intramedullary PEEK rod placed. Biomechanical testing included non
destructive bi-planar 4 point bending, torsion testing, and destructive axial
compression. Testing produced the responses of failure load (N) in axial
compression, stiffness (N/mm or N/ degrees ) in axial compression, torsion,
lateral-medial, and caudal-cranial 4 point bending. Screw position within the
PEEK-rods was determined after explantation. RESULTS: The PEEK-rod constructs
were significantly stiffer in axial compression (P < .005), lateral-medial 4
point bending (P < .001), and in torsional loading (P < .031) than the Steinman
pin constructs. There was no significant difference between the constructs for
stiffness in caudal-cranial 4 point bending (P = .32). The PEEK-rod constructs
failed at a significantly higher load than the Steinmann pin constructs (P <
.001). All constructs failed by yielding through plastic deformation. Each screw
penetrated the PEEK rod in all constructs but the position of the screw varied.
CONCLUSION: PEEK-rod constructs failed at significantly higher loads and were
significantly stiffer in 4 point lateral-medial bending, axial compression, and
torsion when compared with Steinmann pin constructs.
PMID- 25132258
TI - Retinoic acid receptor-alpha up-regulates proopiomelanocortin gene expression in
AtT20 corticotroph cells.
AB - Cushing's disease is a disorder caused by excessive ACTH secretion from a
corticotroph tumor of the pituitary gland. Although its standard therapy is a
transsphenoidal surgery, innovation of novel medical treatments for the disease
is urgently necessary. Retinoic acid (RA) has been reported to suppress
adrenocorticotropic hormone (ACTH) secretion in Cushing's disease. However, the
role of RA receptor (RAR) in proopiomelanocortin (Pomc) gene expression remains
uncertain. We here examined the involvement of RARalpha in Pomc regulation using
AtT20 corticotroph cells. Surprisingly, a synthetic RARalpha agonist Am80
increased Pomc mRNA expression, CRH-induced ACTH secretion, and Pomc promoter
activity. Small interfering RNA-mediated RARalpha-knockdown suppressed both basal
and Am80-induced Pomc promoter activity. RARalpha-overexpression dose-dependently
increased Pomc promoter activity. Pomc promoter mutation analysis revealed that
both Tpit and NeuroD1 binding elements were responsible for the Am80-mediated
effect. Am80 increased Tpit expression while RAR antagonist LE540 suppressed the
increase. Tpit-overexpression increased Pomc promoter activity. Mammalian two
hybrid assay revealed that Am80 induced NeuroD1-RARalpha interaction. NeuroD1
overexpression enhanced the Am80-induced Pomc promoter activity, which was
suppressed by NeuroD1 truncated mutant-overexpression. RARalpha thus positively
regulates ACTH secretion/Pomc gene expression through interaction with NeuroD1
and Tpit expression increase. The present observation will be useful for the
future development of the RA/retinoid-derived therapeutics of the disease.
PMID- 25132259
TI - [Nursing and the humanization of the end- of-life care within healthcare
systems].
AB - The reflection upon the humanisation of the end-of-life process within healthcare
systems and the implication of healthcare professionals is the main objective of
this article. The evolution of the model of care and nurses leadership role at
the end-of-life process is evaluated. This analysis starts from the first
European references regarding advance wills, made in 1997 at the Oviedo
Convention, until the introduction of the idea of advance directives incorporated
into Spanish law in 2002. It sets the concept of advance planning in health
related decisions, which establishes a process of voluntary dialogue where every
person can clarify values, preferences and wishes regarding the final moments of
life, with the support of the healthcare professionals.
PMID- 25132260
TI - CCN5/WISP-2 promotes growth arrest of triple-negative breast cancer cells through
accumulation and trafficking of p27(Kip1) via Skp2 and FOXO3a regulation.
AB - The matricellular protein CCN5/WISP-2 represents a promising target in triple
negative breast cancer (TNBC) because treatment or induced activation of CCN5 in
TNBC cells promotes cell growth arrest at the G0/G1 phase, reduces cell
proliferation and delays tumor growth in the xenograft model. Our studies found
that the p27(Kip1) tumor suppressor protein is upregulated and relocalized to the
nucleus from cytoplasm by CCN5 in these cells and that these two events
(upregulation and relocalization of p27(Kip1)) are critical for CCN5-induced
growth inhibition of TNBC cells. In the absence of CCN5, p27(Kip1) resides mostly
in the cytoplasm, which is associated with the aggressive nature of cancer cells.
Mechanistically, CCN5 inhibits Skp2 expression, which seems to stabilize the
p27(Kip1) protein in these cells. On the other hand, CCN5 also recruits FOXO3a to
mediate the transcriptional regulation of p27(Kip1). The recruitment of FOXO3a is
achieved by the induction of its expression and activity through shifting from
cytoplasm to the nucleus. Our data indicate that CCN5 blocks PI3K/AKT signaling
to dephosphorylate at S318, S253 and Thr32 in FOXO3a for nuclear relocalization
and activation of FOXO3a. Moreover, inhibition of alpha6beta1 receptors
diminishes CCN5 action on p27(Kip1) in TNBC cells. Collectively, these data
suggest that CCN5 effectively inhibits TNBC growth through the accumulation and
trafficking of p27(Kip1) via Skp2 and FOXO3a regulation, and thus, activation of
CCN5 may have the therapeutic potential to kill TNBC.
PMID- 25132261
TI - Neuropeptide Y receptor Y5 as an inducible pro-survival factor in neuroblastoma:
implications for tumor chemoresistance.
AB - Neuroblastoma (NB) is a pediatric tumor of neural crest origin with heterogeneous
phenotypes. Although low-stage tumors carry a favorable prognosis, >50% of high
risk NB relapses after treatment with a fatal outcome. Thus developing therapies
targeting refractory NB remains an unsolved clinical problem. Brain-derived
neurotrophic factor (BDNF) and its TrkB receptor are known to protect NB cells
from chemotherapy-induced cell death, while neuropeptide Y (NPY), acting via its
Y2 receptor (Y2R), is an autocrine proliferative and angiogenic factor crucial
for maintaining NB tumor growth. Here we show that in NB cells, BDNF stimulates
the synthesis of NPY and induces expression of another one of its receptors, Y5R.
In human NB tissues, the expression of NPY and Y5R positively correlated with the
expression of BDNF and TrkB. Functionally, BDNF triggered Y5R internalization in
NB cells, whereas Y5R antagonist inhibited BDNF-induced p44/42 mitogen-activated
protein kinase activation and its pro-survival activity. These observations
suggested TrkB-Y5R transactivation that resulted in cross-talk between their
signaling pathways. Additionally, NPY and Y5R were upregulated in a BDNF
independent manner in NB cells under pro-apoptotic conditions, such as serum
deprivation and chemotherapy, as well as in cell lines and tissues derived from
posttreatment NB tumors. Blocking Y5R in chemoresistant NB cells rich in this
receptor sensitized them to chemotherapy-induced apoptosis and inhibited their
growth in vivo by augmenting cell death. In summary, the NPY/Y5R axis is an
inducible survival pathway activated in NB by BDNF or cellular stress. Upon such
activation, Y5R augments the pro-survival effect of BDNF via its interactions
with TrkB receptor and exerts an additional BDNF-independent anti-apoptotic
effect, both of which contribute to NB chemoresistance. Therefore, the NPY/Y5R
pathway may become a novel therapeutic target for patients with refractory NB,
thus far an incurable form of this disease.
PMID- 25132262
TI - N-terminus-modified Hec1 suppresses tumour growth by interfering with kinetochore
microtubule dynamics.
AB - Mitotic proteins are attractive targets to develop molecular cancer therapeutics
due to the intimate interdependence between cell proliferation and mitosis. In
this work, we have explored the therapeutic potential of the kinetochore (KT)
protein Hec1 (Highly Expressed in Cancer protein 1) as a molecular target to
produce massive chromosome missegregation and cell death in cancer cells. Hec1 is
a constituent of the Ndc80 complex, which mediates KT-microtubule (MT)
attachments at mitosis and is upregulated in various cancer types. We expressed
Hec1 fused with enhanced green fluorescent protein (EGFP) at its N-terminus MT
interaction domain in HeLa cells and showed that expression of this modified
Hec1, which localized at KTs, blocked cell proliferation and promoted apoptosis
in tumour cells. EGFP-Hec1 was extremely potent in tumour cell killing and more
efficient than siRNA-induced Hec1 depletion. In striking contrast, normal cells
showed no apparent cell proliferation defects or cell death following EGFP-Hec1
expression. Live-cell imaging demonstrated that cancer cell death was associated
with massive chromosome missegregation within multipolar spindles after a
prolonged mitotic arrest. Moreover, EGFP-Hec1 expression was found to increase KT
MT attachment stability, providing a molecular explanation for the abnormal
spindle architecture and the cytotoxic activity of this modified protein.
Consistent with cell culture data, EGFP-Hec1 expression was found to strongly
inhibit tumour growth in a mouse xenograft model by disrupting mitosis and
inducing multipolar spindles. Taken together, these findings demonstrate that
stimulation of massive chromosome segregation defects can be used as an anti
cancer strategy through the activation of mitotic catastrophe after a multipolar
mitosis. Importantly, this study represents a clear proof of concept that
targeting KT proteins required for proper KT-MT attachment dynamics constitutes a
powerful approach in cancer therapy.
PMID- 25132263
TI - BRCA1-IRIS inactivation sensitizes ovarian tumors to cisplatin.
AB - Ovarian cancer is the first in mortalities among gynecologic cancers in the
United States, often due to late diagnosis and/or acquired platinum-resistant
recurrences. This study investigates whether BRCA1-IRIS is a novel treatment
target for ovarian cancers and in platinum-resistant recurrences. Here we show
that more than half of the ovarian cancer samples analyzed showed BRCA1-IRIS and
survivin overexpression and lacked nuclear FOXO3a expression. Normal ovarian
epithelial cells overexpressing BRCA1-IRIS formed metastasis in mice when
injected in the peritoneal cavity, whereas aggressive ovarian cancer cell lines
failed to form tumors or metastases in mice when BRCA1-IRIS was silenced in them.
We show that BRCA1-IRIS activates two autocrine signaling loops, brain-derived
neurotrophic factor/tyrosine kinase B receptor (BDNF/TrkB) and neuregulin 1
(NRG1)/ErbB2. These loops are involved in anoikis resistance and metastasis
promotion. These loops operate in several ovarian cancer cell lines, and BRCA1
IRIS silencing or inactivation using a novel inhibitory peptide renders both non
functional and promoted cell death. In a mouse xenograft model, BRCA1-IRIS
inactivation using this novel inhibitory peptide resulted in significant
reduction in ovarian tumor growth. More importantly, this treatment sensitized
ovarian tumors to low cisplatin concentrations. Taken together, these data
strongly suggest that BRCA1-IRIS and/or BDNF/TrkB and NRG1/ErbB2 could serve as
rational therapeutic targets for advanced ovarian cancers.
PMID- 25132264
TI - K63-linked ubiquitination of FANCG is required for its association with the Rap80
BRCA1 complex to modulate homologous recombination repair of DNA interstand
crosslinks.
AB - DNA interstrand crosslinks (ICLs) are extremely deleterious lesions that are
repaired by homologous recombination (HR) through coordination of Fanconi anemia
(FA) proteins and breast cancer susceptibility gene 1 (BRCA1) product, but the
exact role these proteins have remains unclear. Here we report that FANCG was
modified by the addition of lysine63-linked polyubiquitin chains (K63Ub) in
response to DNA damage. We show that FANCG K63Ub was dispensable for
monoubiquitination of FANCD2, but was required for FANCG to interact with the
Rap80-BRCA1 (receptor-associated protein 80-BRCA1) complex for subsequent
modulation of HR repair of ICLs induced by mitomycin C. Mutation of three lysine
residues within FANCG to arginine (K182, K258 and K347, 3KR) reduced FANCG K63Ub
modification, as well as its interaction with the Rap80-BRCA1 complex, and
therefore impeded HR repair. In addition, we demonstrated that K63Ub-modified
FANCG was deubiquitinated by BRCC36 complex in vitro and in vivo. Inhibition of
BRCC36 resulted in increased K63Ub modification of FANCG. Taken together, our
results identify a new role of FANCG in HR repair of ICL through K63Ub-mediated
interaction with the Rap80-BRCA1 complex.
PMID- 25132265
TI - Endonuclease G initiates DNA rearrangements at the MLL breakpoint cluster upon
replication stress.
AB - MLL (myeloid/lymphoid or mixed-lineage leukemia) rearrangements are frequent in
therapy-related and childhood acute leukemia, and are associated with poor
prognosis. The majority of the rearrangements fall within a 7.3-kb MLL breakpoint
cluster region (MLLbcr), particularly in a 0.4-kb hotspot at the intron11-exon12
boundary. The underlying mechanisms are poorly understood, though multiple
pathways including early apoptotic signaling, accompanied by high-order DNA
fragmentation, have been implicated. We introduced the MLLbcr hotspot in an EGFP
based recombination reporter system and demonstrated enhancement of both
spontaneous and genotoxic treatment-induced DNA recombination by the MLLbcr in
various human cell types. We identified Endonuclease G (EndoG), an apoptotic
nuclease, as an essential factor for MLLbcr-specific DNA recombination after
induction of replication stress. We provide evidence for replication stress
induced nuclear accumulation of EndoG, DNA binding by EndoG as well as cleavage
of the chromosomal MLLbcr locus in a manner requiring EndoG. We demonstrate
additional dependency of MLLbcr breakage on ATM signaling to histone H2B
monoubiquitinase RNF20, involved in chromatin relaxation. Altogether our findings
provide a novel mechanism underlying MLLbcr destabilization in the cells of
origin of leukemogenesis, with replication stress-activated, EndoG-mediated
cleavage at the MLLbcr, which may serve resolution of the stalled forks via
recombination repair, however, also permits MLL rearrangements.
PMID- 25132267
TI - Anoikis resistance is a critical feature of highly aggressive ovarian cancer
cells.
AB - High-grade serous ovarian cancer is an aggressive form of epithelial ovarian
cancer (EOC), and accounts for the majority of deaths due to EOC. The critical
cellular processes and underlying molecular mechanisms that define this
malignancy remain poorly understood. Using a syngeneic murine model, we
investigated the changes that accompanied the progression to increased
aggressiveness induced by in vivo passage of mouse EOC cells. We found that
enhanced anoikis resistance was a key cellular process associated with greater
aggressiveness and tumorigenicity in vivo. Biochemical studies revealed that the
enhanced anoikis resistance was associated with the activation of the Src/Akt/Erk
signaling pathway. A higher rate of metabolism and autophagy were also associated
with increased anoikis resistance. Blocking these pathways with specific
inhibitors and/or genetic modifications significantly increased anoikis in vitro
and inhibited tumor development in vivo. In addition, we demonstrated that
similar signaling pathways were also involved in a human EOC cell line model.
Collectively, our data suggest that anoikis resistance represents a critical and
a distinguishing feature underlying the aggressiveness of ovarian cancer cells.
PMID- 25132266
TI - MicroRNA regulons in tumor microenvironment.
AB - Cancer initiation and progression are defined by the behavior of cancer cells per
se and the development of tumor tissues, both of which are modulated by crosstalk
between cancer cells and the surrounding microenvironment. Advances in cancer
research have highlighted the significance of constant evolution of the tumor
microenvironment, leading to tumor formation, metastasis and refractoriness to
therapy. MicroRNAs (miRNAs) are small non-coding RNAs that function as major
players of posttranscriptional gene regulation in diverse biological processes.
They function as both tumor suppressors and promoters in many aspects of the
autonomous behavior of cancer cells. Theoretically, dysfunction in the gene
regulatory networks of cancer cells is one of the major driving forces for
alterations of ostensibly normal surrounding cells. In this context, the core
targets of miRNAs, termed miRNA regulons, are currently being expanded to include
various modulators of the tumor microenvironment. Recent advances have
highlighted two important roles played by miRNAs in the evolution of tumor
microenvironments: miRNAs in tumor cells transform the microenvironment via non
cell-autonomous mechanisms, and miRNAs in neighboring cells stabilize cancer
hallmark traits. These observations epitomize the distal and proximal functions
of miRNAs in tumor microenvironments, respectively. Such regulation by miRNAs
affects tumor angiogenesis, immune invasion and tumor-stromal interactions. This
review summarizes recent findings on the mechanisms of miRNA-mediated regulation
of tumor microenvironments, with a perspective on the design of therapeutic
interventions.
PMID- 25132268
TI - Single-cell gene expression signatures reveal melanoma cell heterogeneity.
AB - It is well established that tumours are not homogenous, but comprise cells with
differing invasive, proliferative and tumour-initiating potential. A major
challenge in cancer research is therefore to develop methods to characterize cell
heterogeneity. In melanoma, proliferative and invasive cells are characterized by
distinct gene expression profiles and accumulating evidence suggests that cells
can alternate between these states through a process called phenotype switching.
We have used microfluidic technology to isolate single melanoma cells grown in
vitro as monolayers or melanospheres or in vivo as xenografted tumours and
analyse the expression profiles of 114 genes that discriminate the proliferative
and invasive states by quantitative PCR. Single-cell analysis accurately
recapitulates the specific gene expression programmes of melanoma cell lines and
defines subpopulations with distinct expression profiles. Cell heterogeneity is
augmented when cells are grown as spheres and as xenografted tumours. Correlative
analysis identifies gene-regulatory networks and changes in gene expression under
different growth conditions. In tumours, subpopulations of cells that express
specific invasion and drug resistance markers can be identified amongst which is
the pluripotency factor POUF51 (OCT4) whose expression correlates with the
tumorigenic potential. We therefore show that single-cell analysis can be used to
define and quantify tumour heterogeneity based on detection of cells with
specific gene expression profiles.
PMID- 25132269
TI - DNA damage response and prostate cancer: defects, regulation and therapeutic
implications.
AB - DNA damage response (DDR) includes the activation of numerous cellular activities
that prevent duplication of DNA lesions and maintain genomic integrity, which is
critical for the survival of normal and cancer cells. Specific genes involved in
the DDR such as BRCA1/2 and P53 are mutated during prostate cancer progression,
while various oncogenic signaling such as Akt and c-Myc are activated, enhancing
the replication stress and increasing the genomic instability of cancer cells.
These events may render prostate cancer cells particularly sensitive to
inhibition of specific DDR pathways, such as PARP in homologous recombination DNA
repair and Chk1 in cell cycle checkpoint and DNA repair, creating opportunities
for synthetic lethality or synergistic cytotoxicity. Recent reports highlight the
critical role of androgen receptor (AR) as a regulator of DDR genes, providing a
rationale for combining DNA-damaging agents or targeted DDR inhibitors with
hormonal manipulation or AR inhibition as treatment for aggressive disease. The
aims of this review are to discuss specific DDR defects in prostate cancer that
occur during disease progression, to summarize recent advances in understanding
the regulation of DDR in prostate cancer, and to present potential therapeutic
opportunities through combinational targeting of the intact components of DDR
signaling pathways.
PMID- 25132270
TI - CHK1 overexpression in T-cell acute lymphoblastic leukemia is essential for
proliferation and survival by preventing excessive replication stress.
AB - Checkpoint kinase 1 (CHK1) is a key component of the ATR (ataxia telangiectasia
mutated and Rad3-related)-dependent DNA damage response pathway that protect
cells from replication stress, a cell intrinsic phenomenon enhanced by oncogenic
transformation. Here, we show that CHK1 is overexpressed and hyperactivated in T
cell acute lymphoblastic leukemia (T-ALL). CHEK1 mRNA is highly abundant in
patients of the proliferative T-ALL subgroup and leukemia cells exhibit
constitutively elevated levels of the replication stress marker phospho-RPA32 and
the DNA damage marker gammaH2AX. Importantly, pharmacologic inhibition of CHK1
using PF-004777736 or CHK1 short hairpin RNA-mediated silencing impairs T-ALL
cell proliferation and viability. CHK1 inactivation results in the accumulation
of cells with incompletely replicated DNA, ensuing DNA damage, ATM/CHK2
activation and subsequent ATM- and caspase-3-dependent apoptosis. In contrast to
normal thymocytes, primary T-ALL cells are sensitive to therapeutic doses of PF
004777736, even in the presence of stromal or interleukin-7 survival signals.
Moreover, CHK1 inhibition significantly delays in vivo growth of xenotransplanted
T-ALL tumors. We conclude that CHK1 is critical for T-ALL proliferation and
viability by downmodulating replication stress and preventing ATM/caspase-3
dependent cell death. Pharmacologic inhibition of CHK1 may be a promising
therapeutic alternative for T-ALL treatment.
PMID- 25132271
TI - The dual-acting chemotherapeutic agent Alchemix induces cell death independently
of ATM and p53.
AB - Topoisomerase inhibitors are in common use as chemotherapeutic agents although
they can display reduced efficacy in chemotherapy-resistant tumours, which have
inactivated DNA damage response (DDR) genes, such as ATM and TP53. Here, we
characterise the cellular response to the dual-acting agent, Alchemix (ALX),
which is a modified anthraquinone that functions as a topoisomerase inhibitor as
well as an alkylating agent. We show that ALX induces a robust DDR at nano-molar
concentrations and this is mediated primarily through ATR- and DNA-PK- but not
ATM-dependent pathways, despite DNA double strand breaks being generated after
prolonged exposure to the drug. Interestingly, exposure of epithelial tumour cell
lines to ALX in vitro resulted in potent activation of the G2/M checkpoint, which
after a prolonged arrest, was bypassed allowing cells to progress into mitosis
where they ultimately died by mitotic catastrophe. We also observed effective
killing of lymphoid tumour cell lines in vitro following exposure to ALX,
although, in contrast, this tended to occur via activation of a p53-independent
apoptotic pathway. Lastly, we validate the effectiveness of ALX as a
chemotherapeutic agent in vivo by demonstrating its ability to cause a
significant reduction in tumour cell growth, irrespective of TP53 status, using a
mouse leukaemia xenograft model. Taken together, these data demonstrate that ALX,
through its dual action as an alkylating agent and topoisomerase inhibitor,
represents a novel anti-cancer agent that could be potentially used clinically to
treat refractory or relapsed tumours, particularly those harbouring mutations in
DDR genes.
PMID- 25132272
TI - TGF-beta signaling alters the pattern of liver tumorigenesis induced by Pten
inactivation.
AB - Hepatocarcinogenesis results from the accumulation of genetic and epigenetic
changes in liver cells. A common mechanism through which these alterations induce
liver cancer is by deregulating signaling pathways. A number of signaling
pathways, including the PI3K/PTEN/AKT and transforming growth factor beta (TGF
beta) pathways have been implicated in normal liver development as well as in
cancer formation. In this study, we assessed the effect of the TGF-beta signaling
pathway on liver tumors induced by phosphatase and tensin homolog (Pten) loss.
Inactivation of only the TGF-beta receptor type II, Tgfbr2, in the mouse liver
(Tgfbr2(LKO)) had no overt phenotype, while inactivation of Pten alone
(Pten(LKO)), resulted in the formation of both hepatocellular carcinomas and
cholangiocarcinomas (CC). Interestingly, deletion of both Pten and Tgfbr2
(Pten(LKO);Tgfbr2(LKO)) in the mouse liver resulted in a dramatic shift in tumor
type to predominantly CC. Assessment of the PI3K/PTEN/AKT pathway revealed
increased phosphorylation of AKT and glycogen synthase kinase 3 beta (GSK-3beta)
in both the Pten(LKO) and Pten(LKO);Tgfbr2(LKO) mice, suggesting that this
pathway is constitutively active regardless of the status of the TGF-beta
signaling pathway. However, phosphorylation of p70 S6 kinase was observed in the
liver of all three phenotypes (Tgfbr2(LKO), Pten(LKO), Pten(LKO);Tgfbr2(LKO))
indicating that the loss of Tgfbr2 and/or Pten leads to an increase in this
signaling pathway. Analysis of markers of liver progenitor/stem cells revealed
that the loss of TGF-beta signaling resulted in increased expression of c-Kit and
CD133. Furthermore, in addition to increased c-Kit and CD133, Scf and EpCam
expression were also increased in the double knock-out mice. These results
suggest that the alteration in tumor types between the Pten(LKO) mice and
Pten(LKO);Tgfbr2(LKO) mice is secondary to the altered regulation of stem-cell
features induced by the loss of TGF-beta signaling.
PMID- 25132275
TI - Desquamative inflammatory vaginitis.
AB - Desquamative inflammatory vaginitis (DIV) is an uncommon form of chronic purulent
vaginitis. It occurs mainly in Caucasians with a peak occurrence in the
perimenopause. Symptoms and signs are nonspecific; DIV is a diagnosis of
exclusion, and other causes of purulent vaginitis should be excluded. The main
symptoms include purulent discharge, vestibulo-vaginal irritation, and
dyspareunia. Examination of vaginal walls shows signs of inflammation with
increased erythema and petechiae. Through microscopy (wet mount) of the vaginal
secretions, DIV is defined by an increase in inflammatory cells and parabasal
epithelial cells (immature squamous cells). Vaginal flora is abnormal and pH is
always elevated above 4.5. Although etiology and pathogenesis remain unknown, the
favorable response to anti-inflammatory agents suggests that the etiology is
immune mediated. Either local vaginal clindamycin or vaginal corticosteroids are
adequate treatment. As a chronic condition, maintenance treatment should be
considered as relapse is common.
PMID- 25132273
TI - Biodegradable poly(ester urethane)urea elastomers with variable amino content for
subsequent functionalization with phosphorylcholine.
AB - While surface modification is well suited for imparting biomaterials with
specific functionality for favorable cell interactions, the modification of
degradable polymers would be expected to provide only temporary benefit. Bulk
modification by incorporating pendant reactive groups for subsequent
functionalization of biodegradable polymers would provide a more enduring
approach. Towards this end, a series of biodegradable poly(ester urethane)urea
elastomers with variable amino content (PEUU-NH2 polymers) were developed.
Carboxylated phosphorycholine was synthesized and conjugated to the PEUU-NH2
polymers for subsequent bulk functionalization to generate PEUU-PC polymers.
Synthesis was verified by proton nuclear magnetic resonance, X-ray photoelectron
spectroscopy and attenuated total reflection Fourier transform infrared
spectroscopy. The impact of amine incorporation and phosphorylcholine conjugation
was shown on mechanical, thermal and degradation properties. Water absorption
increased with increasing amine content, and further with PC conjugation. In wet
conditions, tensile strength and initial modulus generally decreased with
increasing hydrophilicity, but remained in the range of 5-30 MPa and 10-20 MPa,
respectively. PC conjugation was associated with significantly reduced platelet
adhesion in blood contact testing and the inhibition of rat vascular smooth
muscle cell proliferation. These biodegradable PEUU-PC elastomers offer
attractive properties for applications as non-thrombogenic, biodegradable
coatings and for blood-contacting scaffold applications. Further, the PEUU-NH2
base polymers offer the potential to have multiple types of biofunctional groups
conjugated onto the backbone to address a variety of design objectives.
PMID- 25132277
TI - Surgery of the vulva in vulvar cancer.
AB - The standard radical mutilating surgery for the treatment of invasive vulval
carcinoma is, today, being replaced by a conservative and individualised
approach. Surgical conservative modifications that are currently considered safe,
regarding vulval lesion, are separate skin vulval-groin incisions, drawn
according to the lesion diameter, and wide local radical excision or partial
radical vulvectomy with 1-2 cm of clinically clear surgical margins. Regarding
inguinofemoral lymph nodes management, surgical conservative modifications not
compromising patient survival are omission of groin lymphadenectomy only when
tumour stromal invasion is <= 1 mm, unilateral groin lymphadenectomy only in well
lateralised early lesions and total or radical inguinofemoral lymphadenectomy
with preservation of femoral fascia when full groin resection is needed. Sentinel
lymph node dissection is a promising technique but it should not be routinely
employed outside referral centres. Pelvic nodes are better managed by radiation.
Locally advanced vulval carcinoma can be managed by ultraradical surgery,
exclusive radiotherapy or chemoradiation.
PMID- 25132276
TI - Vulvar dermatosis.
AB - Vulvar dermatoses are inflammatory conditions responsible for chronic or
recurrent itching and soreness. The lesions are either circumscribed to the vulva
or associated with extragenital localizations which may help to assess the
diagnosis. They should be differentiated from infectious or neoplastic diseases
which may have clinical similarities. As opposed to the majority of all
dermatoses that have a benign and regular course, lichen sclerosus or lichen
planus could exceptionally foster the occurrence of an epithelial cancer
precursor which may evolve to squamous cell carcinoma. Topical corticosteroids
are the mainstay treatment of vulvar dermatosis. We do not know if the treatment
of vulvar lichen sclerosus and vulvar lichen planus prevents squamous cell
carcinoma.
PMID- 25132274
TI - Curcumin-functionalized silk materials for enhancing adipogenic differentiation
of bone marrow-derived human mesenchymal stem cells.
AB - Curcumin, a natural phenolic compound derived from the plant Curcuma longa, was
physically entrapped and stabilized in silk hydrogel films, and its influence on
human bone marrow-derived mesenchymal stem cells (hBMSC) was assessed related to
adipogenic differentiation. The presence of curcumin significantly reduced the
silk gelation time and changed the porous morphology of gel matrix, but did not
change the formation of the silk beta-sheet structure. Based on
spectrofluorimetric analysis, curcumin most likely interacted with hydrophobic
residues in silk, interacting with the beta-sheet domains formed in the
hydrogels. The antioxidant activity of silk film-associated curcumin remained
functional over at least one month in both the dry and hydrated state. Negligible
curcumin was released from silk hydrogel films over 48 h incubation in aqueous
solution. For hBMSC cultured on silk films containing more than 0.25 mg ml(-1)
curcumin, cell proliferation was inhibited, while adipogenesis was significantly
promoted based on transcripts as well as Oil Red O staining. When hBMSC were
cultured in media containing free curcumin, both proliferation and adipogenesis
of hBMSC were inhibited when curcumin concentrations exceeded 5 MUM, which is
more than 1000 times higher than the level of curcumin released from the films in
aqueous solution. Thus, silk film-associated curcumin exhibited different effects
on hBMSC proliferation and differentiation compared with curcumin in solution.
PMID- 25132278
TI - The effects of an epithelial barrier protective cationic aerosol on allergen
induced airway inflammation in asthma: a randomized, placebo-controlled clinical
trial.
AB - Inhaled cationic airway lining modulator (iCALM) is a cationic aerosol therapy
comprised of 1.29% calcium chloride dissolved in 0.9% isotonic saline that
enhances the biophysical barrier function of the airway lining fluid and primes
the host defense response. It's ability to attenuate bronchitis caused by inhaled
particles was investigated using an allergen-inhalation model in a proof-of
concept study. In a randomized, double-blind, placebo-controlled cross-over trial
of 6 mild atopic steroid-naive asthmatic subjects, 3 doses of iCALM were well
tolerated and they attenuated allergen-induced increase in sputum eosinophils,
and levels of IL-5, MCP-1 and eotaxin. This study provides an opportunity to
investigate the role of enhancing epithelial barrier to decrease airway
inflammation provoked by inhaled particles in a variety of airway diseases.
PMID- 25132280
TI - Does weight loss in overweight or obese women improve fertility treatment
outcomes? A systematic review.
AB - This systematic review assessed the effect of weight loss in overweight and/or
obese women undergoing assisted reproductive technology (ART) on their subsequent
pregnancy outcome. Weight losses achieved by diet and lifestyle changes, very-low
energy diets, non-surgical medical interventions and bariatric surgery translated
into significantly increased pregnancy rates and/or live birth in overweight
and/or obese women undergoing ART in 8 of the 11 studies reviewed. In addition,
regularization of the menstrual pattern, a decrease in cancellation rates, an
increase in the number of embryos available for transfer, a reduction in the
number of ART cycles required to achieve pregnancy and a decrease in miscarriage
rates were reported. There were also a number of natural conceptions in five of
the six studies that reported this outcome. Non-surgical medical weight loss
procedures and bariatric surgery induced the greatest weight losses, but their
use, as well as that of very-low-energy diets, for weight loss prior to ART
requires careful consideration. While the overall quality of the studies included
in this review was poor, these results support the clinical recommendation of
advising overweight and/or obese women to lose weight prior to ART. Prospective
randomized controlled trials are required to establish efficacious evidence-based
guidelines for weight loss interventions in overweight and/or obese women prior
to ART treatment.
PMID- 25132281
TI - Long-term right ventricular support with a centrifugal ventricular assist device
placed in the right atrium.
AB - This case series outlines the technique and results of right ventricular assist
device (RVAD) support with the off-label use of the centrifugal HeartWare HVAD
(HeartWare Inc., Framingham, MA, USA) for long-term support. Four patients in our
institution have been implanted with BiVADs, using the Heartware device as the
RVAD, and supported for between 117 days and 772 days. Three of the patients have
been successfully supported for over 18 months. Three patients have successfully
been transplanted and one patient remains on the device, now approaching two
years of support. None of the patients have had RVAD device-related
complications.
PMID- 25132279
TI - Characterization, mutagenesis and mechanistic analysis of an ancient algal sterol
C24-methyltransferase: Implications for understanding sterol evolution in the
green lineage.
AB - Sterol C24-methyltransferases (SMTs) constitute a group of sequence-related
proteins that catalyze the pattern of sterol diversity across eukaryotic
kingdoms. The only gene for sterol alkylation in green algae was identified and
the corresponding catalyst from Chlamydomonas reinhardtii (Cr) was characterized
kinetically and for product distributions. The properties of CrSMT were similar
to those predicted for an ancient SMT expected to possess broad C3-anchoring
requirements for substrate binding and formation of 24beta-methyl/ethyl
Delta(25(27))-olefin products typical of primitive organisms. Unnatural
Delta(24(25))-sterol substrates, missing a C4beta-angular methyl group involved
with binding orientation, convert to product ratios in favor of Delta(24(28))
products. Remodeling the active site to alter the electronics of Try110 (to Leu)
results in delayed timing of the hydride migration from methyl attack of the
Delta(24)-bond, that thereby produces metabolic switching of product ratios in
favor of Delta(25(27))-olefins or impairs the second C1-transfer activity.
Incubation of [27-(13)C]lanosterol or [methyl-(2)H3]SAM as co-substrates
established the CrSMT catalyzes a sterol methylation pathway by the "algal"
Delta(25(27))-olefin route, where methylation proceeds by a conserved SN2
reaction and de-protonation proceeds from the pro-Z methyl group on lanosterol
corresponding to C27. This previously unrecognized catalytic competence for an
enzyme of sterol biosynthesis, together with phylogenomic analyses, suggest that
mutational divergence of a promiscuous SMT produced substrate- and phyla-specific
SMT1 (catalyzes first biomethylation) and SMT2 (catalyzes second biomethylation)
isoforms in red and green algae, respectively, and in the case of SMT2 selection
afforded modification in reaction channeling necessary for the switch in
ergosterol (24beta-methyl) biosynthesis to stigmasterol (24alpha-ethyl)
biosynthesis during the course of land plant evolution.
PMID- 25132282
TI - A randomised clinical trial of 10-day concomitant therapy and standard triple
therapy for Helicobacter pylori eradication.
AB - BACKGROUND: As a result of increased resistance to antibiotics, Helicobacter
pylori eradication rates using standard triple therapy have been declining. AIM:
To validate the efficacy and tolerability of a concomitant regimen as a first
line treatment for H. pylori infection. METHODS: A total of 348 naive H. pylori
infected patients from six hospitals in Korea were randomly assigned to
concomitant therapy and standard triple therapy groups. The concomitant regimen
consisted of 30 mg of lansoprazole, 1g of amoxicillin, 500 mg of clarithromycin,
and 500 mg of metronidazole, twice daily for 10 days. The standard triple regimen
consisted of 30 mg of lansoprazole, 1g of amoxicillin, and 500 mg of
clarithromycin, twice daily for 10 days. RESULTS: Concomitant and standard
eradication rates were 78.7% (137/174) vs. 70.7% (123/174) by intention-to-treat
(p=0.084) and 88.7% (133/150) vs. 78.4% (120/153) by per-protocol (p=0.016),
respectively. The two groups were similar with regard to the incidence of adverse
events. CONCLUSIONS: Although 10-day concomitant therapy was validated as a
suboptimal treatment option for the treatment of H. pylori infection, this
regimen is expected to be a promising starting point in the development of an
optimal treatment regimen for H. pylori infection.
PMID- 25132283
TI - Is high-viscosity glass-ionomer-cement a successor to amalgam for treating
primary molars?
AB - OBJECTIVES: To assess and compare the cumulative survival rate of amalgam and
atraumatic restorative treatment (ART) restorations in primary molars over 3
years. METHODS: 280 children aged 6-7 years old were enrolled in a cluster
randomized controlled clinical trial using a parallel group design covering two
treatment groups: conventional restorative treatment with amalgam (CRT) and
atraumatic restorative treatment (ART) using a high-viscosity glass-ionomer
(HVGIC) Ketac Molar Easymix. Three pedodontists placed 750 restorations (364
amalgam and 386 ART in 126 and 154 children, respectively) which were evaluated
at 0.5, 1, 2 and 3 years. The proportional hazard rate regression model with
frailty correction, ANOVA and Wald tests, and the Jackknife procedure were
applied in analysing the data. RESULTS: The cumulative survival rates over 3
years for all, single- and multiple-surface CRT/amalgam restorations (72.6%,
93.4%, 64.7%, respectively) were no different from those of comparable ART/HVGIC
restorations (66.8%; 90.1% and 56.4%, respectively) (p=0.10). Single-surface
restorations had higher survival rates than multiple-surface restorations for the
both treatment procedures (p<0.0001). A higher proportion of restorations failed
because of mechanical reasons (94.8%) than of secondary caries (5.2%). No
difference in reasons for restoration failures between all types of amalgam and
ART/HVGIC restorations were observed (p=0.24). SIGNIFICANCE: The high-viscosity
glass-ionomer used in this study in conjunction with the ART is a viable option
for restoring carious dentin lesions in single surfaces in vital primary molars.
PMID- 25132284
TI - The determinants of home healthcare robots adoption: an empirical investigation.
AB - BACKGROUND: Home healthcare robots promise to make clinical information available
at the right place and time, thereby reducing error and increasing safety and
quality. However, it has been frequently reported that more than 40% of previous
information technology (IT) developments have failed or been abandoned due to the
lack of understanding of the sociotechnical aspects of IT. OBJECTIVE: Previous
home healthcare robots research has focused on technology development and
clinical applications. There has been little discussion of associated social,
technical and managerial issues that are arguably of equal importance for robot
success. To fill this knowledge gap, this research aims to understand the
determinants of home healthcare robots adoption from these aspects by applying
technology acceptance theories. METHODS: We employed both qualitative and
quantitative methods. The participants were recruited from home healthcare
agencies located in the U.S. (n=108), which included both patients and healthcare
professionals. We collected data via a survey study to test a research model.
RESULTS: The usage intention of home healthcare robots is a function of social
influence, performance expectancy, trust, privacy concerns, ethical concerns and
facilitating conditions. Among them, social influence is the strongest predictor.
Monitoring vital signs and facilitating communication with family and medication
reminders are the most preferable tasks and applications for robots. CONCLUSION:
Sociotechnical factors play a powerful role in explaining the adoption intention
for home healthcare robots. The findings provide insights on how home healthcare
service providers and robot designers may improve the success of robot
technologies.
PMID- 25132285
TI - Comparison of Chromogenic In Situ Hybridization and Fluorescence In Situ
Hybridization for the Evaluation of MDM2 Amplification in Adipocytic Tumors.
AB - BACKGROUND: Atypical lipomatous tumor/well-differentiated liposarcoma (ALT-WDLPS)
and dedifferentiated liposarcoma (DDLPS) are characterized cytogenetically by a
12q13-15 amplification involving the mouse double minute 2 (MDM2) oncogene.
Fluorescence in situ hybridization (FISH) is used frequently to detect this
amplification and aid with the diagnosis of these entities, which is difficult by
morphology alone. Recently, bright-field in situ hybridization techniques such as
chromogenic in situ hybridization (CISH) have been introduced for the
determination of MDM2 amplification status. METHODS: The present study compared
the results of FISH and CISH for detecting MDM2 amplification in 41 cases of
adipocytic tumors. Amplification was defined in both techniques as a MDM2/CEN12
ratio of 2 or greater. RESULTS: Eleven cases showed amplification with both FISH
and CISH, and 26 cases showed no amplification with both methods. Two cases had
discordant results between CISH and FISH, and two cases were not interpretable by
CISH. CONCLUSION: CISH is advantageous for allowing pathologists to evaluate the
histologic and molecular alterations occurring simultaneously in a specimen.
Moreover, CISH is found to be more cost- and time-efficient when used with
automation, and the signals do not quench over time. CISH technique is a reliable
alternative to FISH in the evaluation of adipocytic tumors for MDM2
amplification.
PMID- 25132286
TI - The Ser680Asn polymorphism in the follicle-stimulating hormone receptor gene is
associated with the ovarian response in controlled ovarian hyperstimulation.
AB - OBJECTIVE: Polymorphisms in the follicle-stimulating hormone receptor (FSHR) gene
are reported to be associated with the ovarian response in controlled ovarian
hyperstimulation (COH), although there remains some discordance between studies.
Here, using the largest patient sample to date, we evaluated the association of
the p.Ser680Asn (S(680)N) polymorphism in the FSHR gene with the outcome of COH.
DESIGN: Cohort study. SETTING: Medical academy and hospital. PATIENTS: A total of
1250 infertile Chinese women undergoing IVF/ICIS-ET treatment were included.
MEASURES: The association between an FSHR polymorphism (S(680)N) and the ovarian
response was analysed. Genotyping was performed by utilizing direct sequencing
and the Sequenom MassARRAY iPLEX platform. Follicular fluid oestradiol (E2) and
follicle-stimulating hormone (FSH) concentrations were determined using
electrochemiluminesence immunoassays. The ovarian response parameters were
analysed based on the FSHR genotypes. The odds ratios (ORs) and 95% confidence
intervals (95% CIs) were calculated for the risk genotypes and alleles. RESULTS:
There were linear correlations between the basal FSH level, exogenous
gonadotropin consumption, and oocytes retrieved and the Ser680 alleles. Patients
in the homozygous SS group demonstrated higher basal FSH levels, required more
dosage of exogenous gonadotropin for ovarian stimulation, and had fewer numbers
of oocytes retrieved compared with patients in the homozygous NN and heterozygous
groups. Logistic regression analysis revealed that the OR of a poor ovarian
response for the NS genotype was 1.79 (95% CI 1.28-2.61; P < 0.001), whereas that
for the SS genotype was 2.25 (95% CI 1.40-3.58; P < 0.001) after adjusting for
age, BMI and basal FSH level. The concentration of E2 in the follicular fluid was
significantly higher in subjects with the NN genotype than the SS genotype (772
+/- 545 ng/ml vs. 1299 +/- 504 ng/ml). CONCLUSIONS: Follicle-stimulating hormone
receptor gene polymorphism at position 680 is associated with different ovarian
responses to controlled ovarian hyperstimulation.
PMID- 25132287
TI - Concise review: Exploring miRNAs--toward a better understanding of hematopoiesis.
AB - Hematopoiesis is governed by a multidimensional regulatory network involving both
intrinsic and extrinsic factors that control self-renewal and differentiation of
hematopoietic stem cells (HSCs) through the coordination of influences that
affect cell fate. Increasing evidence indicates that microRNAs (miRNAs), short
noncoding RNAs of approximately 22 nucleotides, play a central role in
orchestrating these regulatory mechanisms to modulate the multiple entities of
hematopoietic function in a cell-type specific manner, including self-renewal,
lineage commitment, and survival of HSCs as well as their microenvironmental
crosstalk. Here, we summarize the current understanding regarding the regulatory
effects of miRNA on hematopoietic cells, thus enlightening their role in fine
tuning HSC function and hematopoietic homeostasis.
PMID- 25132288
TI - Identification of a Plasmodium falciparum inhibitor-2 motif involved in the
binding and regulation activity of protein phosphatase type 1.
AB - The regulation of Plasmodium falciparum protein phosphatase type 1 (PfPP1)
activity remains to be deciphered. Data from homologous eukaryotic type 1 protein
phosphatases (PP1) suggest that several protein regulators should be involved in
this essential process. One such regulator, named PfI2 based on its primary
sequence homology with eukaryotic inhibitor 2 (I2), was recently shown to be able
to interact with PfPP1 and to inhibit its phosphatase activity, mainly through
the canonical 'RVxF' binding motif. The details of the structural and functional
characteristics of this interaction are investigated here. Using NMR
spectroscopy, a second site of interaction is suggested to reside between
residues D94 and T117 and contains the 'FxxR/KxR/K' binding motif present in
other I2 proteins. This site seems to play in concert/synergy with the 'RVxF'
motif to bind PP1, because only mutations in both motifs were able to abolish
this interaction completely. However, regarding the structure/function
relationship, mutation of either the 'RVxF' or 'FxxR/KxR/K' motif is more
drastic, because each mutation prevents the capacity of PfI2 to trigger germinal
vesicle breakdown in microinjected Xenopus oocytes. This indicates that the tight
association of the PfI2 regulator to PP1, mediated by a two-site interaction, is
necessary to exert its function. Based on these results, the use of a peptide
derived from the 'FxxR/KxR/K' PfI2 motif was investigated for its potential
effect on Plasmodium growth. This peptide, fused at its N-terminus to a
penetrating sequence, was shown to accumulate specifically in infected
erythrocytes and to have an antiplasmodial effect.
PMID- 25132289
TI - Papua New Guinea vision-specific quality of life questionnaire: a new patient
reported outcome instrument to assess the impact of impaired vision.
AB - BACKGROUND: The aim of this study was to develop and validate a new vision
specific quality of life (VS QoL) instrument and to assess the impact of vision
impairment and eye disease on the quality of life of adults in Papua New Guinea
(PNG). DESIGN: This study was designed as community based cross-sectional.
PARTICIPANTS: Six hundred fourteen adults aged 18 and above were included in this
study. METHODS: Focus groups and interviews guided development of a 41-item
instrument. Two valid subscales of the instrument were obtained using pilot data
after an iterative item reduction process guided by Rasch-based parameters. The
person measures (in logits) of 614 participants were used to assess quality of
life using univariate and multivariate regression analysis. MAIN OUTCOME
MEASURES: Rasch logits. RESULTS: Rasch analysis confirmed a 17-item instrument
containing an 8-item activity limitation subscale and a 9-item well-being
subscale. Both subscales were unidimensional and demonstrated good fit
statistics, measurement precisions and absence of significant differential item
functioning. A consistent deterioration in vision-specific quality of life was
independently and significantly associated with levels of vision. Severity of
vision impairment and ocular morbidity were independently associated with
activity limitation and emotional well-being. Participants with refractive error
had lower quality of life score than those with no ocular abnormality but higher
score than those with cataract and other eye diseases. CONCLUSIONS: The 17-item
PNG-VS QoL instrument is a valid and reliable instrument for the assessment of
impact of impaired vision on quality of life in PNG. Vision-specific quality of
life was significantly worse among participants who were older and less-educated,
had lower income and have had ocular morbidities.
PMID- 25132290
TI - Carbon dioxide as a protecting group: highly efficient and selective catalytic
access to cyclic cis-diol scaffolds.
AB - The efficient and highly selective formation of a wide range of (hetero)cyclic
cis-diol scaffolds using aminotriphenolate-based metal catalysts is reported. The
key intermediates are cyclic carbonates, which are obtained in high yield and
with high levels of diastereo- and chemoselectivity from the parent oxirane
precursors and carbon dioxide. Deprotection of the carbonate structures affords
synthetically useful cis-diol scaffolds with different ring sizes that
incorporate various functional groups. This atom-efficient method allows the
simple construction of diol synthons using inexpensive and accessible precursors
and green metal catalysts and showcases the use of CO2 as a temporary protecting
group.
PMID- 25132291
TI - On the International Society of Zoological Sciences: reflections upon a momentous
decade.
PMID- 25132293
TI - Predators, energetics and fitness drive neonatal reproductive failure in red
squirrels.
AB - Neonatal reproductive failure should occur when energetic costs of parental
investment outweigh fitness benefits. However, little is known about the drivers
of neonatal reproductive failure in free-ranging species experiencing continuous
natural variation in predator abundance and in the energetic and fitness costs
and benefits associated with parental investment. Long-term comprehensive studies
are required to better understand how biotic, abiotic and life-history conditions
interact to drive occurrences of reproductive failure in the wild. Using 24 years
(1987-2011) of reproductive data from a northern boreal population of North
American red squirrels in south-western Yukon, we examined the effects of
predator abundance, energetics (resource availability, ambient temperature and
litter size) and fitness benefits (probability of overwinter juvenile survival
and maternal age) on occurrences of neonatal reproductive failure (494/2670
reproductive attempts; 18.5%). Neonatal reproductive failure was driven by a
combination of predator abundance, and the energetic and fitness costs and
benefits of parental investment. The abundance of mustelids and maternal age was
positively related to the occurrence of neonatal reproductive failure. High
energy costs associated with a combination of low resource availability and cold
ambient temperatures or large litters, corresponded to increased occurrences of
neonatal reproductive failure. However, the strength of these relationships was
influenced by variation in juvenile overwinter survival (i.e. fitness benefits).
We provide evidence that predation pressure is an important driver of neonatal
reproductive failure. In addition, we found a trade-off occurs between resource
dependent energetic and fitness costs and benefits of raising the current litter
to independence.
PMID- 25132292
TI - Feasibility of near real-time lesion assessment during radiofrequency catheter
ablation in humans using acoustic radiation force impulse imaging.
AB - BACKGROUND: Visual confirmation of radiofrequency ablation (RFA) lesions during
clinical cardiac ablation procedures could improve procedure efficacy, safety,
and efficiency. It was previously shown that acoustic radiation force impulse
(ARFI) imaging can identify RFA lesions in vitro and in vivo in an animal model.
This is the "first-in-human" feasibility demonstration of intracardiac ARFI
imaging of RFA lesions in patients undergoing catheter ablation for atrial
flutter (AFL) or atrial fibrillation (AF). METHODS AND RESULTS: Patients
scheduled for right atrial (RA) ablation for AFL or left atrial (LA) ablation for
drug refractory AF were eligible for imaging. Diastole-gated intracardiac ARFI
images were acquired using one of two equipment configurations: (1) a Siemens
ACUSON S2000TM ultrasound scanner and 8/10Fr AcuNavTM ultrasound catheter, or (2)
a CARTO 3TM integrated Siemens SC2000TM and 10Fr SoundStarTM ultrasound catheter.
A total of 11 patients (AFL = 3; AF = 8) were imaged. ARFI images were acquired
of ablation target regions, including the RA cavotricuspid isthmus (CTI), and the
LA roof, pulmonary vein ostia, posterior wall, posterior mitral valve annulus,
and the ridge between the pulmonary vein and LA appendage. ARFI images revealed
increased relative myocardial stiffness at ablation catheter contact sites after
RFA and at anatomical mapping-tagged RFA treatment sites. CONCLUSIONS: ARFI
images from a pilot group of patients undergoing catheter ablation for AFL and AF
demonstrate the ability of this technique to identify intra-procedure RFA lesion
formation. The results encourage further refinement of ARFI imaging clinical
tools and continued investigation in larger clinical trials.
PMID- 25132294
TI - Comparison of long-term drug survival and safety of biologic agents in patients
with psoriasis vulgaris.
AB - BACKGROUND: Drug survival (time to drug discontinuation) has recently emerged as
an important parameter reflecting the long-term therapeutic performance in a real
life setting. Biologic drug survival in psoriasis is mainly limited by a gradual
loss of efficacy over time. Previous studies have been limited by small patient
population size and short observation times and yielded discrepant survival times
for different biologics. OBJECTIVES: To calculate the long-term drug survival for
adalimumab, etanercept, infliximab and ustekinumab in a large cohort of real-life
patients with psoriasis vulgaris and to analyse the factors that influence drug
survival. PATIENTS AND METHODS: Data were extracted from the prospective registry
DERMBIO covering all patients with psoriasis vulgaris treated with biologic
agents in the academic centres in Denmark. Drug survival was analysed using the
Kaplan-Meier method. The influence of different covariates on drug survival was
analysed by Cox regression. RESULTS: Included in the analysis were 1867 treatment
series (adalimumab n = 774, etanercept n = 449, infliximab n = 253, ustekinumab n
= 391) administered in 1277 patients for up to 10 years. Drug survival was
significantly longer for ustekinumab than for anti-tumour necrosis factor (TNF)
alpha agents (P < 0.001). Etanercept had the shortest survival time [median
survival 30 months, 95% confidence interval (CI) 25.1-34.9] whereas adalimumab
and infliximab had comparable survival rates (59 months, 95% CI 45.6-72.4; 44
months, 95% CI 33-54.9, respectively). Survival was longer in men [odds ratio
(OR) 1.51, 95% CI 1.31-1.74 vs. women] and in patients who had not previously
received any biologic agent (OR 1.24, 95% CI 1.05-1.46). Loss of efficacy
accounted for 67% of all drug discontinuations. CONCLUSIONS: Ustekinumab has a
significantly longer drug survival than the anti-TNF-alpha agents. Switching from
one biologic to another is associated with an impairment of drug survival.
Preventing loss of efficacy is a major area of medical need in the biologic
therapy of psoriasis and the strategies that improve drug survival should be
further investigated.
PMID- 25132295
TI - The use of enzyme-coupled magnetic nanoparticles for studying the spectra of
unusual substrates of mushroom tyrosinase by direct surface-assisted laser
desorption/ionisation and high-resolution electrospray ionisation quadrupole
quadrupole-time-of-flight mass spectrometry.
AB - RATIONALE: Tyrosinase-coupled magnetic particles (EMPs) were used to demonstrate
that resorcinol-containing tyrosinase inhibitors are oxidised by tyrosinase only
in the presence of the enzyme's classic substrate. This shows the potential for
the application of EMPs as a non-organic matrix for monitoring enzymatic
conversion of a novel substrate family directly on-the-spot, principally due to
minimal enzyme requirement per analysis. METHODS: Tyrosinase was covalently
coupled to core-shell-type silica-coated iron oxide magnetic nanoparticles (EMPs)
that were applied as non-organic SALDI matrix suitable for studying low-mass
compounds using a classic matrix-assisted laser desorption/ionisation time-of
flight (MALDI-TOF) mass spectrometer. Because of the dual function of the EMPs -
enzyme host and non-organic matrix - we describe this ionisation method as Enzyme
coupled Nanoparticles-Assisted LDI-MS (ENALDI-MS). Supplementary studies of the
enzymatic conversion of glabridin and 3-(2,4-dihydroxyphenyl)propionic acid
(DHPA) were conducted by high-resolution electrospray ionisation quadrupole
quadrupole-time-of-flight mass spectrometry (ESI-QqTOF-MS). RESULTS: The initial
experiment involving EMPs as non-organic matrix (ENALDI-MS) showed enzymatic
conversion of glabridin, a strong tyrosinase inhibitor, only in the presence of L
Tyr, the classic tyrosinase substrate. These findings were evaluated by ESI-QqTOF
MS proving that glabridin and DHPA are converted into the corresponding quinones
by tyrosinase only in the presence of the auxiliary monophenol or o-diphenol
substrates (L-Tyr and catechin, respectively) capable of regenerating the active
site of tyrosinase. CONCLUSIONS: EMPs were shown to be useful as a non-organic
matrix to monitor enzymatic conversion of the novel tyrosinase substrate family
directly on-the-spot with a minimal enzyme consumption (6.5 pmol/spot). Results
obtained by ENALDI-MS were fully confirmed by ESI-QqTOF-MS demonstrating that
resorcinol-containing tyrosinase inhibitors may be oxidised by the enzyme in the
presence of its classic substrates.
PMID- 25132296
TI - Cleavage of phosphorus-carbon (P-C) bonds of alpha-amino phosphonates with
intramolecular hydrogen migration in the gas phase using electrospray ionization
tandem mass spectrometry.
AB - RATIONALE: alpha-Amino phosphonates with intrinsic biological activities have
been used in a wide variety of applications. Because of the widespread existence
of natural organophosphorus compounds containing P-C bonds such as the alpha
amino phosphonates, it is important to investigate the gas-phase chemistry of P-C
bonds in order to determine their basic properties, which might provide some
insights into their biosynthesis and catalytic cleavage. METHODS: Twenty alpha
amino phosphonates were successfully synthesized and their fragmentation behavior
was systematically investigated using in-solution deuterium labeling in
combination with high-resolution Fourier transform ion cyclotron resonance
(FTICR) electrospray ionization tandem mass spectrometry. RESULTS: The
fragmentation pathways of twenty alpha-amino phosphonates with different chemical
structures were systematically studied. In general, P-C bonds could be easily
cleaved via a novel intramolecular hydrogen atom migration from the amino group
to the phosphoryl group through a five-membered-ring intermediate in the gas
phase. A possible mechanism of the rearrangement of alpha-amino phosphonates is
proposed. CONCLUSIONS: An interesting intramolecular hydrogen atom migration
between the amino and phosphoryl groups was observed with cleavage of the P-C
bond in the molecule through a five-membered-ring intermediate. This
characteristic fragmentation pathway not only provides some insights into the
basic chemistry of compounds with P-C bonds, but could also have some
applications in the structural determination of the alpha-amino phosphonate
analogues.
PMID- 25132298
TI - Gravitational sampling electrospray ionization mass spectrometry for real-time
reaction monitoring.
AB - RATIONALE: The elucidation of chemical reaction mechanisms has attracted
tremendous interest in recent years. Here, gravitational sampling electrospray
ionization mass spectrometry (GS-ESI-MS) is used to explore a simple method for
the real-time monitoring of chemical and biochemical reactions. METHODS: A sample
solution in a stainless steel sample well is directly delivered through a fused
silica capillary due to the forces of gravity, capillary action, and
electroosmotic flow (EOF). Analyte ions are continuously generated via
electrospray ionization from the capillary tip when a high voltage is applied on
the sample well. RESULTS: Liquid solutions (<5 MUL) of small organic compounds
(e.g., crystal violet) and large biomolecules (e.g., reserpine, angiotensin II,
and insulin) were directly analyzed via GS-ESI-MS. In addition, the technique was
successfully applied to continuously monitor chemical [e.g. chelation of
ethylenediaminetetraacetic acid (EDTA) with copper(II), and addition-elimination
of aminophenol and acetic anhydride] and biochemical (e.g., unfolding of
cytochrome c) reactions in real time, where chelation complexes, reaction
intermediates, and protein conformation changes were observed. CONCLUSIONS: GS
ESI-MS is a very simple modification of the ESI technique that does not require
sample delivery pumps or nebulizer gases. It is particularly suitable for the
analysis of liquid samples and the real-time monitoring of inorganic/organic
chemical or biochemical reactions.
PMID- 25132297
TI - Low-temperature plasma for compositional depth profiling of crosslinking organic
multilayers: comparison with C60 and giant argon gas cluster sources.
AB - RATIONALE: For organic electronics, device performance can be affected by
interlayer diffusion across interfaces. Time-of-flight secondary ion mass
spectrometry (TOF-SIMS) can resolve buried structures with nanometer resolution,
but instrument artifacts make this difficult. Low-temperature plasma (LTP) is
suggested as a way to prepare artifact-free surfaces for accurate determination
of chemical diffusion. METHODS: A model organic layer system consisting of three
1 nm delta layers of 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (BCP)
separated by three 30 nm layers of tris(8-hydroxyquinolinato)aluminum (Alq3) was
used to evaluate the effectiveness of LTP etching for the preparation of crater
edge surfaces for subsequent compositional depth profile analysis. This was
compared with depth profiles obtained using an instrument equipped with an argon
cluster sputter source. RESULTS: The quality of the depth profiles was determined
by comparing the depth resolutions of the BCP delta layers. The full width at
half maximum gave depth resolutions of 6.9 nm and 6.0 nm using LTP, and 6.2 nm
and 5.8 nm using argon clusters. In comparison, the 1/e decay length of the
trailing edge gave depth resolutions of 2.0 nm and 1.8 nm using LTP, and 3.5 nm
and 3.4 nm using argon clusters. CONCLUSIONS: The comparison of the 1/e decay
lengths showed that LTP can determine the thickness and composition of the buried
structures without instrument artifacts. Although it does suffer from contaminant
deposition, LTP was shown to be a viable option for preparing crater edges for a
more accurate determination of buried structures.
PMID- 25132299
TI - Caution on the use of NBS 30 biotite for hydrogen-isotope measurements with on
line high-temperature conversion systems.
AB - RATIONALE: The supply of NBS 30 biotite is nearly exhausted. During measurements
of NBS 30 and potential replacements, reproducible delta(2)HVSMOW-SLAP values
could not be obtained by three laboratories using high-temperature conversion
(HTC) systems. The cause of this issue has been investigated using the silver
tube technique for hydrogen-isotope measurements of water. METHODS: The
delta(2)HVSMOW-SLAP values of NBS 30 biotite, other biotites, muscovites, and
kaolinite with different particle sizes, along with IAEA-CH-7 polyethylene, and
reference waters and NBS 22 oil that were sealed in silver-tube segments, were
measured. The effect of absorbed water on mineral surfaces was investigated with
waters both enriched and depleted in (2)H. The quantitative conversion of
hydrogen from biotite into gaseous hydrogen as a function of mass and particle
size was also investigated. RESULTS: The delta(2)HVSMOW-SLAP values of NBS 30
obtained by three laboratories were as much as 21 0/00 too high compared with the
accepted value of -65.7 0/00, determined by conventional off-line measurements.
The experiments showed a strong correlation between grain size and the
delta(2)HVSMOW-SLAP value of NBS 30 biotite, but not of biotites with lower iron
content. The delta(2)HVSMOW-SLAP values of NBS 30 as a function of particle size
show a clear trend toward -65.7 0/00 with finer grain size. CONCLUSIONS:
Determination of the delta(2)HVSMOW-SLAP values of hydrous minerals and of NBS 30
biotite by on-line HTC systems coupled to isotope-ratio mass spectrometers may be
unreliable because hydrogen in this biotite may not be converted quantitatively
into molecular hydrogen. Extreme caution in the use and interpretation of
delta(2)HVSMOW-SLAP on-line measurements of hydrous minerals is recommended.
PMID- 25132300
TI - Interlaboratory assessment of nitrous oxide isotopomer analysis by isotope ratio
mass spectrometry and laser spectroscopy: current status and perspectives.
AB - RATIONALE: In recent years, research and applications of the N2O site-specific
nitrogen isotope composition have advanced, reflecting awareness of the
contribution of N2O to the anthropogenic greenhouse effect, and leading to
significant progress in instrument development. Further dissemination of N2O
isotopomer analysis, however, is hampered by a lack of internationally agreed
gaseous N2O reference materials and an uncertain compatibility of different
laboratories and analytical techniques. METHODS: In a first comparison approach,
eleven laboratories were each provided with N2O at tropospheric mole fractions
(target gas T) and two reference gases (REF1 and REF2). The laboratories analysed
all gases, applying their specific analytical routines. Compatibility of
laboratories was assessed based on N2O isotopocule data for T, REF1 and REF2.
Results for T were then standardised using REF1 and REF2 to evaluate the
potential of N2O reference materials for improving compatibility between
laboratories. RESULTS: Compatibility between laboratories depended on the
analytical technique: isotope ratio mass spectrometry (IRMS) results showed
better compatibility for delta(15)N values, while the performance of laser
spectroscopy was superior with respect to N2O site preference. This comparison,
however, is restricted by the small number of participating laboratories applying
laser spectroscopy. Offset and two-point calibration correction of the N2O
isotopomer data significantly improved the consistency of position-dependent
nitrogen isotope data while the effect on delta(15)N values was only minor.
CONCLUSIONS: The study reveals that for future research on N2O isotopocules,
standardisation against N2O reference material is essential to improve
interlaboratory compatibility. For atmospheric monitoring activities, we suggest
N2O in whole air as a unifying scale anchor.
PMID- 25132301
TI - Fragmentation of negative ions from N-linked carbohydrates: part 6. Glycans
containing one N-acetylglucosamine in the core.
AB - RATIONALE: Negative ion collision-induced dissociation (CID) spectra of N-glycans
contain many diagnostic ions that provide more structural information than
positive ion spectra. EndoH or endoS release of glycans from glycoproteins, as
used by many investigators, cleaves glycans between the GlcNAc residues of the
chitobiose core leaving the glycan without the reducing-terminal GlcNAc residue.
However, their negative ion CID spectra do not appear to have been studied in
detail. This paper examines the CID and ion mobility properties of these endoH
released glycans to determine if the missing GlcNAc influences the production of
diagnostic fragment ions. METHODS: N-Glycans were released from ribonuclease B,
ovalbumin and gp120 with endoH to give high-mannose and hybrid glycans, and from
IgG with endoS to produce biantennary complex glycans, all missing the reducing
terminal GlcNAc residue. Negative ion CID and travelling wave ion mobility
spectra were recorded with a Waters Synapt G2 mass spectrometer using nanospray
sample introduction. RESULTS: The majority of glycans yielded CID spectra
exhibiting the same diagnostic fragments, which were equivalently informative, as
the fully released structures. However, the ability of ion mobility to separate
isomers was generally found to be inferior to its use with the full glycans
despite the smaller nature of the compounds. The exception was the partial
resolution of a pair of biantennary monogalactosylated glycans from IgG where, as
chloride adducts, slight separation of the isomers was observed. CONCLUSIONS: The
results show that the CID spectra of endoH- and endoS-released glycans are as
useful as the corresponding spectra of the intact glycans (as released by PNGase
F) in providing structural information on N-glycans.
PMID- 25132302
TI - Transformation of gas-phase amino acid clusters to dipeptides: a nice approach to
demonstrate the formation of prebiotic peptides.
AB - RATIONALE: Exploring prebiotic developments is a fascinating area of research
which is continually drawing the attention of the scientific community. It is
probable that first the biomolecules were formed and then they became aggregated
to generate life. Formation of one such biomolecules (peptide ions) is shown in
the present experiments. METHODS: All amino acid solutions for recording mass
spectra were prepared in 3:6.9:0.1 (v/v/v) acetonitrile/water/formic acid at a
concentration of 50 MUM. The studies were performed using a Bruker MicroTOF QII
mass spectrometer. Before carrying out experiments in the collision cell,
atmospheric pressure in-source fragmentations were also performed. The formation
of different chemical species was detected with high-resolution mass
spectrometry. RESULTS: Here, we show experimentally the formation of amino acid
cluster ions of varied populations, when a solution of an amino acid was injected
into an electrospray ionization quadrupole time-of-flight (ESI-QTOF) mass
spectrometer. During in-source fragmentation/collision cell fragmentation, the
non-covalent interaction between two identical amino acids forms either the [M2 +
H](+) dimer cluster ion and/or the [M2 + K](+) adduct ion which, by elimination
of one molecule of water, form the covalent linked dipeptide. CONCLUSIONS: After
the formation of the amino acid cluster, it was established that the creation of
the dipeptides, by a covalent bond resulting from the loss of a water molecule,
was the initial step towards the formation of the primordial peptides.
PMID- 25132303
TI - Modification of a gas chromatography/atmospheric pressure chemical ionisation
time-of-flight mass spectrometer as an alternative to automated atmospheric
pressure solids analysis probe.
AB - RATIONALE: The atmospheric pressure solids analysis probe (ASAP) has been
successfully introduced into laboratories as a routine analytical tool but the
technique is labour-intensive and is not easily automated. This paper describes
the modifications made to an existing atmospheric pressure gas chromatography
(APGC) system to enable the automated analysis of samples that would have
otherwise been analysed by ASAP. METHODS: Liquid samples were injected into a 1 m
piece of fused silica guard column using a standard split/splitless gas
chromatography (GC) inlet, oven and autosampler. A novel timing delay circuit was
developed and integrated into the system to control acquisition start times and a
bespoke heating block/calibrant delivery system was used to transport either the
calibration or reference compound into the ionisation source. RESULTS: The
modified system has allowed the successful analysis of those samples requiring
ASAP to be carried out in a fully automated manner using APGc. The analysis is
rapid and can be carried out in less than 2 min. The results obtained are
directly comparable with those obtained by ASAP. A typical mass accuracy of
better than 5 mm/z units was achieved, allowing the molecules to be identified
based on their elemental formulae. CONCLUSIONS: An existing APGC system has been
successfully modified and is suitable for the automatic analysis of samples
normally analysed by ASAP. The APGC instrument incorporates the use of a novel
reference compound and delivery system which allows accurate mass measurements to
be performed. This and the other modifications described have allowed the
technique to be incorporated into an existing suite of mass spectrometry-based
experiments for use in the characterisation of organic molecules.
PMID- 25132304
TI - Lingual tonsil hypertrophy diagnosed by post-mortem computed tomography in a
difficult airway case.
PMID- 25132305
TI - Of low back pain and moxibustion.
PMID- 25132306
TI - "Moving forward: outlining the plan"-dean's report of the Faculty of Pain
Medicine of the Australian and New Zealand College of Anaesthetists.
PMID- 25132307
TI - Report of the NIH Task Force on research standards for chronic low back pain.
AB - OBJECTIVE: Despite rapidly increasing intervention, functional disability due to
chronic low back pain (cLBP) has increased in recent decades. We often cannot
identify mechanisms to explain the major negative impact cLBP has on patients'
lives. Such cLBP is often termed non-specific, and may be due to multiple
biologic and behavioral etiologies. Researchers use varied inclusion criteria,
definitions, baseline assessments, and outcome measures, which impede comparisons
and consensus. DESIGN: Expert panel and preliminary evaluation of key
recommendations. METHODS: The NIH Pain Consortium charged a Research Task Force
(RTF) to draft standards for research on cLBP. The resulting multidisciplinary
panel developed a 3-stage process, each with a 2-day meeting. RESULTS: The panel
recommended using 2 questions to define cLBP; classifying cLBP by its impact
(defined by pain intensity, pain interference, and physical function); use of a
minimal data set to describe research subjects (drawing heavily on the PROMIS
methodology); reporting "responder analyses" in addition to mean outcome scores;
and suggestions for future research and dissemination. The Pain Consortium has
approved the recommendations, which investigators should incorporate into NIH
grant proposals. CONCLUSION: The RTF believes these recommendations will advance
the field, help to resolve controversies, and facilitate future research
addressing the genomic, neurologic, and other mechanistic substrates of chronic
low back pain. Greater consistency in reporting should facilitate comparisons
among studies and the development of phenotypes. We expect the RTF
recommendations will become a dynamic document, and undergo continual
improvement. PERSPECTIVE: A task force was convened by the NIH Pain Consortium
with the goal of developing research standards for chronic low back pain. The
results included recommendations for definitions, a minimum dataset, reporting
outcomes, and future research. Greater consistency in reporting should facilitate
comparisons among studies and the development of phenotypes.
PMID- 25132310
TI - Fungal phytases: characteristics and amelioration of nutritional quality and
growth of non-ruminants.
AB - Fungal phytases are histidine acid phosphatases, a subclass of acid phosphatases,
which catalyse the hydrolysis of phytic acid resulting in the release of
phosphate moieties and thus mitigate its antinutritional properties. The
supplementation of feed with phytases increases the bioavailability of phosphorus
and minerals in non-ruminant animals and reduces the phosphorus pollution due to
phosphorus excretion in the areas of intensive livestock production. Although
phytases are reported in plants, animals and micro-organisms, fungal sources are
used extensively for the production of phytases on a commercial scale. Phytases
have been produced by fungi in both solid-state fermentation (SSF) and submerged
fermentation (SmF). The fungal phytases are high molecular weight proteins
ranging from 35 to 500 kDa. They are optimally active within pH and temperature
ranges between 4.5 and 6.0, and 45 and 70 degrees C respectively. Phytate
degradation leads to amelioration in the nutritional status of foods and feeds by
improving the availability of minerals, phosphorus and proteins in non-ruminant
animals and human beings and thus mitigates the environmental phosphorus
pollution. Our article focuses on the role of fungal phytases in improving
nutritional value of foods and feeds with concomitant increase in growth of non
ruminant animals and mitigating environmental phosphorus pollution.
PMID- 25132308
TI - Characterizing heat-sensitization responses in suspended moxibustion with high
density EEG.
AB - OBJECTIVE: We have reported "heat-sensitization" responses during suspended
moxibustion, whose occurrence is associated with significantly better therapeutic
effects. The present study aimed to characterize the electrophysiological
features of this interesting phenomenon with high-density electroencephalography
(EEG). METHODS: We performed EEG recording in a group of patients with chronic
low back pain before, during, and after moxibustion treatment at DU3. RESULTS: 12
out of 25 subjects experienced strong heat-sensitization during moxibustion,
which was accompanied by increased power spectral densities (PSDs) at the theta,
alpha, and beta frequency bands. The scalp topographies of averaged power
indicated that the theta and beta PSD changes were most obvious in fronto-central
regions, whereas those of the alpha band were more global. In addition,
nonsensitized and sensitized groups showed distinct activity patterns, with heat
sensitization inducing increased phase coherence at the theta and beta ranges.
CONCLUSIONS: These data were the first objective evidence of heat-sensitization
responses during suspended moxibustion, which were characterized by widespread
oscillatory changes in scalp EEG.
PMID- 25132311
TI - Graphene/polydopamine-modified polytetrafluoroethylene microtube for the
sensitive determination of three active components in Fructus Psoraleae by online
solid-phase microextraction with high-performance liquid chromatography.
AB - Determination of bioactive compounds in traditional Chinese medicines and
biological samples is usually interfered with by coexisting components in
matrices. In this work, we prepared novel multilayer functional
graphene/polydopamine-modified polytetrafluoroethylene microtube for selective
solid-phase microextraction of three bioactive compounds in Fructus Psoraleae.
Functional graphene/polydopamine-modified polytetrafluoroethylene microtube
showed good extraction efficiency toward bavachin, isobavachalcone, and
bavachinin; enrichment from 357- to 737-fold was obtained for these compounds.
For qualitative analysis, an online solid-phase microextraction with high
performance liquid chromatography method was developed, which showed low limits
of detection of 0.02 ng/mL by using UV detection, which is significantly more
sensitive than previously reported methods. The proposed method has been used to
determine bavachin, isobavachalcone, and bavachinin in Fructus Psoraleae, the
contents of three compounds were quantified to be 64.0, 324.0, and 384.5 MUg/g;
recoveries were 93.4-101.1%. The proposed method has also been applied to
determine bavachin, isobavachalcone, and bavachinin in rat plasma samples after
oral administration of Fructus Psoraleae.
PMID- 25132312
TI - Designing the nanobiointerface of fluorescent nanodiamonds: highly selective
targeting of glioma cancer cells.
AB - Core-shell nanoparticles based on fluorescent nanodiamonds coated with a
biocompatible N-(2-hydroxypropyl)methacrylamide copolymer shell were developed
for background-free near-infrared imaging of cancer cells. The particles showed
excellent colloidal stability in buffers and culture media. After conjugation
with a cyclic RGD peptide they selectively targeted integrin alphavbeta3
receptors on glioblastoma cells with high internalization efficacy.
PMID- 25132313
TI - Novel endoscopic diagnosis for bladder cancer.
AB - Advances in endoscopic imaging technology may improve sensitivity for the
detection of bladder cancer and provide a more complete understanding of the
urothelial landscape, and it also may lead to improved short-term and long-term
cancer control. Fluorescence cystoscopy requires intravesical administration of a
photosensitizing agent (5-aminolevulinic acid or hexaminolevulinate), and imaging
with a blue-light endoscopy system demonstrably improves the detection of
papillary and flat bladder lesions compared with conventional white-light
cystoscopy. Prospective phase 3 clinical trials have demonstrated improved
diagnostic ability, enhanced tumor resection, and a small but significant
reduction in recurrence-free survival. Optical coherence tomography delineates
subsurface microarchitecture information about bladder lesions in real time and
has the ability to discriminate between noninvasive and invasive cancers. Narrow
band imaging may augment white-light cystoscopy by providing increased contrast
between normal and abnormal tissue on the basis of neovascularity. Confocal laser
endoscopy has been applied to the urinary tract using thinner probes adapted from
use in gastrointestinal malignancies and provides exquisite images at microscopic
resolution. More technology is on the horizon that may further enhance our
ability to detect and accurately stage bladder tumors and distinguish benign from
malignant or dysplastic lesions.
PMID- 25132314
TI - Predictors of unmet needs and psychological distress in adolescent and young
adult siblings of people diagnosed with cancer.
AB - PURPOSE: Predictors of psychological distress and unmet needs amongst adolescents
and young adults (AYAs) who have a brother or sister diagnosed with cancer were
examined. METHODS: There were 106 AYAs (12-24 years old) who completed
questionnaires covering demographics, psychological distress (Kessler 10), unmet
needs (Sibling Cancer Needs Instrument) and family relationships (Family
Relationship Index; Adult Sibling Relationship Questionnaire; Sibling Perception
Questionnaire (SPQ)). Three models were analysed (demographic variables, cancer
specific variables and family functioning variables) using multiple linear
regression to determine the role of the variables in predicting psychological
distress and unmet needs. RESULTS: Unmet needs were higher for AYA siblings when
treatment was current or a relapse had occurred. Higher scores on the SPQ
Interpersonal subscale indicating a perceived decrease in the quality of
relationships with parents and others were associated with higher levels of
distress and unmet needs. The age and gender of the AYA sibling, whether it was
their brother or sister who was diagnosed with cancer, the age difference between
them, the number of parents living with the AYA sibling, parental birth country,
time since diagnosis, Family Relationship Index, Adult Sibling Relationship
Questionnaire and the SPQ-Communication subscale did not significantly impact
outcome variables. CONCLUSIONS: These results highlight the variables that can
assist in identifying AYA siblings of cancer patients who are at risk and have a
greater need for psychosocial assistance. Variables that may be associated with
increased distress and unmet needs are reported to assist with future research.
The results are also useful in informing the development of targeted psychosocial
support for AYA siblings of cancer patients.
PMID- 25132315
TI - LC-MS/MS analysis of Gegen Qinlian Decoction and its pharmacokinetics after oral
administration to rats.
AB - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed
and validated for the simultaneous determination of 12 constituents of Gegen
Qinlian Decoction (GQD), namely puerarin, daidzein, baicalin, wogonoside,
wogonin, liquiritin, liquiritigenin, berberine, jatrorrhizine, palmatine,
coptisine and glycyrrhetic acid, in rat plasma. The plasma samples were spiked
with the internal standard (IS) carbamazepine acidified with HCl and extracted by
liquid-liquid extraction with ethyl acetate. Chromatographic separation was
achieved on a Shiseido Capcell PAK C18 column utilizing a gradient elution
profile and a mobile phase consisting of (A) 0.1% formic acid in water and (B)
acetonitrile. Detection was performed in the multiple reaction monitoring mode
using electrospray ionization in the positive ion mode at a flow rate of 0.3
mL/min and a run time of 8 min. All of the calibration curves gave good linearity
(r > 0.9930) over the concentration range from 0.6-360 to 16.2-9720 ng/mL for all
components. The intra- and inter-day precisions were <15.0% in terms of the
relative standard deviation, and the accuracies were within +/-13.7% in terms of
the relative error. The method was successfully applied to investigate the
pharmacokinetics of the major active compounds of Gegen Qinlian Decoction after
its oral administration to rats.
PMID- 25132316
TI - Synaptic plasticity under learning challenge.
AB - Memory formation requires changes in neuronal networks connectivity based on
modifications in strength and number of synapses. The mechanisms driving these
changes have been intensively studied, but mostly under naive conditions, i.e. in
animals that have not been cognitively challenged. Better characterization of
synaptic requirements supporting memory formation can emerge from studies
focusing on synaptic changes in memory-encoding structures while or after the
animal model is cognitively challenged. Here, with this concept in mind, we
review the literature describing structural, functional and molecular alterations
developing in the hippocampus when animals are asked to form memories. We also
briefly discuss the interest of this approach for disclosing pathological
mechanisms in memory disorders, which might otherwise not be observed in naive
conditions.
PMID- 25132317
TI - APOE epsilon4 allele is associated with worse performance in memory dimensions of
the mini-mental state examination: the Bambui Cohort Study of Aging.
AB - OBJECTIVE: This study aimed to investigate the correlation between apolipoprotein
E (APOE) epsilon4 and the mini-mental state examination (MMSE) dimension in an
elderly population, using baseline data from the Bambui (Brazil) Cohort Study of
Aging. DESIGN: We conducted a community-based cross-sectional study. SETTING: The
study took place at Bambui city, Minas Gerais State, Southeast Brazil.
PARTICIPANTS: A total of 1408 (87.7%) cohort participants had complete
information on the MMSE and health measures. MEASUREMENTS: The association
between each of five dimensions (concentration, language/praxis, orientation,
attention, and memory) underlying the MMSE and APOE epsilon4 allele was assessed
using multivariate linear regression models. Potential confounding variables
included sociodemographic factors and selected biomarkers. RESULTS: The main
finding is a strong negative association between the presence of APOE epsilon4
allele and memory dimension in the MMSE (fully adjusted beta coefficient = -0.14;
95% confidence interval: -0.27 to -0.04; p = 0.016). No other cognitive
dimensions showed significant associations with the APOE epsilon4 allele.
CONCLUSION: This study is the first to investigate the association between
dimensions of the MMSE, obtained from principal component analysis and APOE
epsilon4 carrier status in community-dwelling older adults taking into account a
range of potential confounding factors. We found a strong negative association
between the presence of APOE epsilon4 allele and scores on memory dimension of
the MMSE, but no effect on other dimensions. Our results reinforce previous data
on the literature that APOE epsilon4 allele has a significant effect on cognitive
performance that can be detected even in screening tests, such as the MMSE.
PMID- 25132318
TI - Depression, dementia and cognition in older people.
PMID- 25132319
TI - Association between inflammatory markers and frailty in institutionalized older
men.
AB - OBJECTIVES: To determine whether higher serum levels of interleukin-6 (IL-6),
tumor necrosis factor-alpha (TNF-alpha), and high sensitivity C-reactive protein
(CRP) were associated with frailty in the older institutionalized men.
PARTICIPANTS: The study enrolled 386 residents from a veterans care home in
northern Taiwan in 2007. All participants were men. Residents younger than 65
years or with acute illness were excluded. METHODS: Frailty status was determined
based on the frailty phenotype (indicators include weight loss, exhaustion, and
low grip strength, slow walking speed). Participants with 3 or more of the
indicators were defined as frail, with 1 or 2 as intermediate frail, with no as
non-frail. Serum IL-6, TNF-alpha, and hsCRP levels were measured using enzyme
linked immunosorbent assay and modeled as tertile for severely skewed
distributions. RESULTS: The mean age of the participants was 81.5+/-4.9 years.
The percentages of frail were 33.2%, intermediate frail 59.1% and nonfrail 7.8%.
Higher IL-6 level was positively associated with the frail status. Adjusting for
age, body mass index, smoking status, and comorbid conditions, serum IL-6 showed
significant trend across frailty categories (P=0.03 [95% CI 1.40-5.24]). No
significant associations of TNF-alpha, and CRP level with frailty were observed.
An IL-6 level of 1.79pg/mL had the optimal predictive value for frailty, with an
area under the receiver operating characteristic (ROC) curve of 0.66 (P=0.01 [95%
CI 0.53-0.78]). CONCLUSION: Higher serum levels of IL-6 were associated with
frailty status in the older institutionalized men with multiple comorbidities.
PMID- 25132321
TI - An octadentate bifunctional chelating agent for the development of stable
zirconium-89 based molecular imaging probes.
AB - (89)Zr-based imaging agents hold great promise as novel radio-tracers in nuclear
medicine. However, insufficient stability of currently used radiometal complexes
in vivo is a safety concern for clinical applications. We herein report the first
octadentate bifunctional chelating agent for the development of (89)Zr-labelled
(bio)conjugates with improved stability.
PMID- 25132320
TI - Accuracy of two continuous glucose monitoring systems: a head-to-head comparison
under clinical research centre and daily life conditions.
AB - AIMS: To assess the accuracy and reliability of the two most widely used
continuous glucose monitoring (CGM) systems. METHODS: We studied the Dexcom(r)G4
Platinum (DG4P; Dexcom, San Diego, CA, USA) and Medtronic Paradigm Veo Enlite
system (ENL; Medtronic, Northridge, CA, USA) CGM systems, in 24 patients with
type 1 diabetes. The CGM systems were tested during 6-day home use and a nested 6
h clinical research centre (CRC) visit. During the CRC visit, frequent venous
blood glucose samples were used as reference while patients received a meal with
an increased insulin bolus to induce an aggravated postprandial glucose nadir. At
home, patients performed at least six reference capillary blood measurements per
day. A Wilcoxon signed-rank test was performed using all data points >=15 min
apart. RESULTS: The overall mean absolute relative difference (MARD) value
[standard deviation (s.d.)] measured at the CRC was 13.6 (11.0)% for the DG4P and
16.6 (13.5)% for the ENL [p < 0.0002, confidence interval of difference (CI
Delta) 1.7-4.3%, n = 530]. The overall MARD assessed at home was 12.2 (12.0)% for
the DG4P and 19.9 (20.5)% for the ENL (p < 0.0001, CI Delta = 5.8-8.7%, n = 839).
During the CRC visit, the MARD in the hypoglycaemic range [<=3.9 mmol/l (70
mg/dl)], was 17.6 (12.2)% for the DG4P and 24.6 (18.8)% for the ENL (p = 0.005,
CI Delta 3.1-10.7%, n = 117). Both sensors showed higher MARD values during
hypoglycaemia than during euglycaemia [3.9-10 mmol/l (70-180 mg/dl)]: for the
DG4P 17.6 versus 13.0% and for the ENL 24.6 versus 14.2%. CONCLUSIONS: During
circumstances of intended use, including both a CRC and home phase, the ENL was
noticeably less accurate than the DG4P sensor. Both sensors showed lower accuracy
in the hypoglycaemic range. The DG4P was less affected by this negative effect of
hypoglycaemia on sensor accuracy than was the ENL.
PMID- 25132322
TI - Three-dimensional characterization of noble-metal nanoparticles and their
assemblies by electron tomography.
AB - New developments in the field of nanomaterials drive the need for quantitative
characterization techniques that yield information down to the atomic scale. In
this Review, we focus on the three-dimensional investigations of metal
nanoparticles and their assemblies by electron tomography. This technique has
become a versatile tool to understand the connection between the properties and
structure or composition of nanomaterials. The different steps of an electron
tomography experiment are discussed and we show how quantitative three
dimensional information can be obtained even at the atomic scale.
PMID- 25132323
TI - Avian influenza H9N2 subtype in Poland--characterization of the isolates and
evidence of concomitant infections.
AB - In April/May 2013, four outbreaks of avian influenza virus (AIV) infections
caused by H9N2 subtype were diagnosed in Poland in fattening turkey flocks
exhibiting a drop in feed and water intake, depression, respiratory signs and
mortality. The subsequent serological survey carried out on samples collected
between June 2012 and September 2013 from 92 poultry flocks detected positive
sera in two additional meat turkey flocks located in the same province. The
analysis of amino acids in the haemagglutinin and neuraminidase glycoproteins
revealed that the detected H9N2 viruses possessed molecular profiles suggestive
of low pathogenicity, avian-like SAalpha2,3 receptor specificity and adaptation
to domestic poultry. Phylogenetic studies showed that these H9N2 AIVs grouped
within the Eurasian clade of wild bird-origin AIVs and had no relationship with
H9N2 AIV circulating in poultry in the Middle East and Far East Asia over the
past decade. Experimentally infected SPF chickens with the index-case H9N2 virus
remained healthy throughout the experiment. On the other hand, ten 3-week-old
commercial turkeys infected via the oculonasal route showed respiratory signs and
mortality (2/10 birds). Additional diagnostic tests demonstrated the consistent
presence of DNA/RNA of Ornithobacterium rhinotracheale, Bordetella avium and,
less frequently, of astro-, rota-, reo-, parvo- and adenoviruses in turkeys both
from field outbreaks and laboratory experiment. Although no microbiological
culture was performed, we speculate that these secondary pathogens could play a
role in the pathogenicity of the current H9N2 infections.
PMID- 25132324
TI - Challenges and potential solutions to educating learners about pediatric complex
care.
AB - OBJECTIVE: To identify existing challenges and potential strategies for providing
complex care training to future pediatricians from a national group of educators.
METHODS: Data were collected from pediatric educators involved in complex care at
the Pediatric Educational Excellence Across the Continuum national meeting.
Participants completed an anonymous 15-item survey adapted from the Association
of American Medical Colleges (AAMC) Best Practices for Better Care initiative and
participated in a focus group to understand the challenges and potential
solutions to pediatric complex care education. Data were analyzed using grounded
theory. RESULTS: Of the 15 participants, 9 (60%) were in educational leadership
positions. All participants provided care to children with medical complexity
(CMC), although 80% (n = 12) reported no formal training. Thematic analysis
revealed learners' challenges in 2 domains: 1) a lack of ownership for the
patient because of decreased continuity, decision-making authority, and autonomy,
as a result of the multitude of care providers and parents' distrust; and 2) a
sense of being overwhelmed as a result of lack of preparedness and disruptions in
work flow. Participants suggested 3 mitigating strategies: being candid about the
difficulties of complex care, discussing the social mandate to care for CMC, and
cultivating humility among learners. CONCLUSIONS: Residency education must
prepare pediatricians to care for all children, regardless of disease. Training
in complex care involves redefining the physician's role so that they are better
equipped to participate in collaboration, empathy and advocacy with CMC. This
study is the first to identify specific challenges and offer potential solutions
to help establish training guidelines.
PMID- 25132325
TI - Lymphocytes subsets reference values in childhood.
AB - Immunophenotyping of blood lymphocyte subsets and activation markers is a basic
tool in the diagnostic process of primary immunodeficiency diseases, its use
becoming more and more widespread as the knowledge about these illnesses
increases. However, the availability of reliable reference values, which need to
be age-matched for the pediatric population, is a pre-requisite for the reliable
interpretation of immunophenotyping data. Aim of this study is to analyze the
lymphocyte subsets and activation markers distribution in children aged 0-18
years referring to the University Hospital of Padova and to create age-matched
reference values expressed by percentiles, thus providing a valuable guideline
for the interpretation of the immunophenotype.
PMID- 25132327
TI - An EBP mentor and unit-based EBP team: a strategy for successful implementation
of a practice change to reduce catheter-associated urinary tract infections.
PMID- 25132326
TI - Melatonin treatment further improves adipose-derived mesenchymal stem cell
therapy for acute interstitial cystitis in rat.
AB - This study tests the hypothesis that combined melatonin and adipose-derived
mesenchymal stem cell (ADMSC, 1.2 * 10(6) given intravenously) treatment offer
superior protection against cyclophosphamide (CYP 150 mg/kg)-induced acute
interstitial cystitis (AIC) in rats. Male adult Sprague-Dawley rats were treated
as follows: sham controls, AIC alone, AIC + melatonin, AIC + ADMSC, and AIC +
melatonin +ADMSC. When melatonin was used, it was given as follows: 20 mg/kg at
30 min after CYP and 50 mg/kg at 6 and 18 hr after CYP. Twenty-four-hour urine
volume, urine albumin level, and severity of hematuria were highest in AIC rats
and lowest in the controls; likewise urine volume was higher in AIC + melatonin
rats than in AIC + ADMSC and AIC + melatonin + ADMSC treated rats; in all cases,
P < 0.001. The numbers of CD14+, CD74+, CD68+, MIP+, Cox-2+, substance P+, cells
and protein expression of IL-6, IL-12, RANTES, TNF-alpha, NF-kappaB, MMP-9, iNOS
(i.e. inflammatory biomarkers), glycosaminoglycan level, expression of oxidized
protein, and protein expression of reactive oxygen species (NOX-1, NOX-2, NOX-4)
in the bladder tissue exhibited an identical pattern compared with that of
hematuria among the five groups (all P < 0.0001). The integrity of epithelial
layer and area of collagen deposition displayed an opposite pattern compared to
that of hematuria among all groups (P < 0.0001). The cellular expressions of
antioxidants (GR, GPx, HO-1, NQO 1) showed a significant progressive increase
form controls to AIC + melatonin + ADMSC (all P < 0.0001). Combined regimen of
melatonin and ADMSC was superior to either alone in protecting against CYP
induced AIC.
PMID- 25132328
TI - Development of category-based induction and semantic knowledge.
AB - Category-based induction is a hallmark of mature cognition; however, little is
known about its origins. This study evaluated the hypothesis that category-based
induction is related to semantic development. Computational studies suggest that
early on there is little differentiation among concepts, but learning and
development lead to increased differentiation based on taxonomic relatedness.
This study reports findings from a new task aimed to (a) examine this putative
increase in semantic differentiation and (b) test whether individual differences
in semantic differentiation are related to category-based induction in 4- to 7
year-old children (N = 85). The results provide the first empirical evidence of
an age-related increase in differentiation of representations of animal concepts
and suggest that category-based induction is related to increased semantic
differentiation.
PMID- 25132329
TI - TPO concentrations and response to romiplostim.
PMID- 25132330
TI - Comparison of hemodynamic performance of the balloon-expandable SAPIEN 3 versus
SAPIEN XT transcatheter valve.
AB - The SAPIEN 3 valve (S3V) is a new-generation transcatheter valve with enhanced
anti-paravalvular leak properties, but no data comparing with earlier
transcatheter valve systems are available. We aimed to compare the hemodynamic
performance of the S3V and the SAPIEN XT valve (SXTV) in a case-matched study
with echo core laboratory analysis. A total of 27 patients who underwent
transcatheter aortic valve replacement (TAVR) with the S3V were matched for
prosthesis size (26 mm), aortic annulus area, and mean diameter measured by
computed tomography, left ventricular ejection fraction, body surface area, and
body mass index with 50 patients treated with the SXTV. The prosthesis size was
determined by oversizing of 1% to 15% of annulus area. Doppler echocardiographic
images collected at baseline and 1-month follow-up were analyzed in a central
echocardiography core laboratory. The need for postdilation was higher in the
SXTV group (20% vs 4%, p=0.047), and mean residual gradient and effective orifice
area were similar in both groups (p>0.05). The incidence of paravalvular aortic
regurgitation was greater with the SXTV (>=mild: 42%, moderate: 8%) than with the
S3V (>=mild: 7%, moderate: 0%; p=0.002 for >=mild vs SXTV). The implantation of
an S3V was the only factor associated with trace or no paravalvular leak after
TAVR (p=0.007). In conclusion, TAVR with the S3V was associated with a very low
rate of paravalvular leaks and need for balloon postdilation, much lower than
that observed with the earlier generation of balloon-expandable valve (SXTV). The
confirmation of these results in a larger cohort of patients will represent a
major step forward in using transcatheter valves for the treatment of aortic
stenosis.
PMID- 25132331
TI - Characteristics of trabeculated myocardium burden in young and apparently healthy
adults.
AB - Increased myocardial trabeculations define noncompaction cardiomyopathy (NCC).
Imaging advancements have led to increasingly common identification of prominent
trabeculations with unknown implications. We quantified and determined the impact
of trabeculations' burden on cardiac function and stretch in a population of
healthy young adults. One hundred adults aged 18 to 35 years (28+/-4 years, 55%
women) without known cardiovascular disease were prospectively studied by
cardiovascular magnetic resonance. Left ventricular (LV) volumes, segmental
function, and ejection fraction (EF) and left atrial volumes were determined.
Thickness and area of trabeculated (T) and dense (D) myocardium were measured for
each standardized LV segment. N-terminal pro-brain natriuretic peptide (Nt-pro
BNP) was measured. Eighteen percent of the subjects had >=1 positive traditional
criteria for NCC, and 11% meet new proposed NCC cardiovascular magnetic resonance
criteria. Trabeculated over dense myocardium ratio (T/D) ratios were uniformly
greater at end-diastole versus end-systole (0.90+/-0.25 vs 0.42+/-0.13,
p<0.0001), in women versus men (0.85+/-0.24 vs 0.72+/-0.19, p=0.006), at anterior
versus nonanterior segments (1.41+/-0.59 vs 0.88+/-0.35, p<0.0001), and at apical
versus nonapical segments (1.31+/-0.56 vs 0.87+/-0.38, p<0.0001). The largest T/D
ratios were associated with lower LVEF (57.0+/-5.3 vs 62+/-5.5, p=0.0001) and
greater Nt-pro-BNP (203+/-98 vs 155+/-103, p=0.04). Multivariable regression
identified greater end-systolic T/D ratios as the strongest independent predictor
of lower LVEF, beyond age and gender, left atrial or LV volumes, and Nt-pro-BNP
(beta=-9.9, 95% CI -15 to 4.9, p<0.001). In conclusion, healthy adults possess
variable amounts of trabeculations that regularly meet criteria for NCC. Greater
trabeculations are associated with decreased LV function. Apparently healthy
young adults with increased trabecular burden possess evidence of mildly impaired
cardiac function.
PMID- 25132332
TI - Relation of time to coronary reperfusion and the development of acute kidney
injury after ST-segment elevation myocardial infarction.
AB - Time to coronary reperfusion and acute kidney injury (AKI) are powerful
prognostic markers in patients with ST-segment elevation myocardial infarction
(STEMI) who underwent percutaneous coronary intervention (PCI); however, no
information to date is present regarding the association between time to
reperfusion and AKI. We evaluated whether time to reperfusion predicts the risk
of developing AKI in patients with STEMI who underwent primary PCI. Medical
records of 417 patients admitted to our department from January 2008 to July
2013, for STEMI, and treated with primary PCI were reviewed. Patients were
stratified by time to coronary reperfusion tertiles, and their records were
assessed for the occurrence of AKI after PCI. Mean age was 61 +/- 13 years, and
346 patients (83%) were men. The cut-off points for the time to reperfusion
tertiles were <120, 120 to 300, and >300 minutes. Patients having longer time to
reperfusion had significantly more AKI complicating the course of STEMI (3% vs
11% vs 13%, p = 0.007) and had significantly higher serum creatinine change
throughout hospitalization (0.13 vs 0.18 vs 0.21 mg/dl, p = 0.003). In a
multivariable regression model, time to coronary reperfusion emerged as an
independent predictor of AKI and to the maximal change in serum creatinine. In
conclusion, longer time to coronary reperfusion is an independent risk factor for
the development of AKI in patients with STEMI who underwent primary PCI.
PMID- 25132333
TI - Transportation behaviour of fluopicolide and its control effect against
Phytophthora capsici in greenhouse tomatoes after soil application.
AB - BACKGROUND: Fluopicolide, a novel benzamide fungicide, was registered for control
of oomycete pathogens, including Phytophthora capsici. In this study,
fluopicolide (5% SC) was applied in soil at rates of 1.5, 3 and 6 L ha(-1) [the
normal (ND), double (DD) and quadruple dosages (QD) respectively] to investigate
its transportation behaviour and control efficiency on tomato blight as a soil
treatment agent. RESULTS: The results showed that fluopicolide applied to soil
could be absorbed by tomato roots and then transplanted to stems and leaves. It
could exist in tomato roots for more than 30 days, and in leaves and stems until
day 20 after application. The decline in fluopicolide in soil was in accordance
with a first-order dynamics equation, with half-lives of 5.33, 4.75 and 5.42 days
for the ND, DD and QD treatments respectively. The control efficiencies of
fluopicolide were better with soil application than with spraying application,
and the inhibition ratios were 93.02, 97.67 and 100 on day 21 for the ND, DD and
QD treatments respectively. CONCLUSION: Soil application of fluopicolide could
control P. capsici in greenhouse tomatoes with high efficiency and long
persistence.
PMID- 25132334
TI - Variation in amphibian response to two formulations of glyphosate-based
herbicides.
AB - Variation in toxicity among formulations and species makes it difficult to
extrapolate results to all species and all formulations of herbicides. The
authors exposed larval wood frogs (Lithobates sylvaticus) from 4 populations to 2
glyphosate-based herbicides, Roundup Weed and Grass Control(r) and Roundup
WeatherMax(r). The 96-h median lethal concentration values for both formulations
varied among the populations (Roundup Weed and Grass Control, 0.14 mg acid
equivalents (a.e.)/L to 1.10 mg a.e./L; Roundup WeatherMax, 4.94 mg a.e./L to
8.26 mg a.e./L), demonstrating that toxicity varies among the formulations and
that susceptibility may differ among populations.
PMID- 25132335
TI - Protective properties of a fusion pneumococcal surface protein A (PspA) vaccine
against pneumococcal challenge by five different PspA clades in mice.
AB - An increase in the appearance of nonvaccine serotypes in both children and adults
with invasive pneumococcal disease (IPD) after introduction of pneumococcal
conjugate vaccine represents a limitation of this vaccine. In this study, we
generated three recombinant pneumococcal surface protein A (PspA) proteins
comprising PspA families 1 and 2, and we examined the reactivity of antisera
raised in mice immunized with a PspA fusion protein in combination with CpG
oligonucleotides plus aluminum hydroxide gel. The protective effects of
immunization with PspA fusion proteins against pneumococcal challenge by strains
with five different PspA clades were also examined in mice. Flow cytometry
demonstrated that PspA3+2-induced antiserum showed the greatest binding of PspA
specific IgG to all five challenge strains with different clades. PspA2+4- or
PspA2+5-induced antiserum showed the lowest binding of PspA-specific IgG to clade
3. Immunization with PspA3+2 afforded significant protection against pneumococcal
challenge by five strains with different clades in mice, but immunization with
PspA2+4 or PspA2+5 failed to protect mice from pneumococcal challenge by strains
with clades 1 and 3. The binding of PspA-specific IgG in antisera raised by three
PspA fusion proteins was examined in 68 clinical isolates from adult patients
with IPD. Immunization of mice with PspA3+2-induced antiserum with a high binding
capacity for clinical isolates expressing clades 1-4, but not clade 5. Our
results suggest that the PspA3+2 vaccine has an advantage over the PspA2+4 or
PspA2+5 vaccine in terms of a broad range of cross-reactivity with clinical
isolates and cross-protection against pneumococcal challenge in mice.
PMID- 25132336
TI - Maternal determinants of timely vaccination coverage among infants in rural
Bangladesh.
AB - BACKGROUND: Timely vaccination, i.e., the receipt of all scheduled vaccinations
in an age-appropriate fashion, is critical for the prevention of deadly diseases
in infants and achievement of the UN Millennium Development Goal to reduce infant
mortality. Infants, especially in rural or underprivileged settings often receive
delayed vaccinations leaving them susceptible to vaccine-preventable illnesses
early in the first year of life. In this study, we examined rates of timely
vaccination among 24,435 infants born in Gaibandha and Rangpur rural districts of
Bangladesh from 2001 to 2007. METHODS: Vaccinations due by 14 weeks of age and
administered through routine government immunization services were assessed using
interviews with enrolled mothers between 11 and 18 weeks postpartum. We created a
Timely Vaccination (TV) score to classify infants as vaccinated fully and on
schedule (TV=1) or not (TV=0), and used multivariable logistic regression to
identify maternal characteristics associated with infant's timely vaccination
status. RESULTS: Our results suggest that only 19% of infants in this cohort
received scheduled vaccinations on time by 11-18 weeks postpartum. Mothers'
engagement in paid employment [OR=1.13, 95% CI: 1.03-1.23], receipt of tetanus
toxoid vaccination [OR=1.24, 95% CI: 1.11-1.38], history of antenatal care
[OR=1.22, 95% CI: 1.12-1.32], or higher socioeconomic status [OR=1.07, 95% CI:
1.03-1.11] were positively associated with timely vaccination of their infants.
Mother's perception of small infant size at birth was negatively associated with
timely vaccination [OR=0.89, 95% CI: 0.82-0.97]. CONCLUSION: Timely vaccination
coverage of infants in rural Gaibandha and Rangpur districts is extremely low.
This analysis identifies important shortcomings associated with the 1-year
vaccination benchmark of routine immunization performance and suggests the need
for specific interventions based on potential maternal determinants as well as
known system and programmatic barriers of timely vaccination among infants in
rural Bangladesh.
PMID- 25132337
TI - Uptake of influenza vaccine in ulcerative colitis.
AB - BACKGROUND: The incidence of vaccine-preventable-disease is increasing. Current
practice guidelines recommend annual influenza vaccination for all inflammatory
bowel disease (IBD) patients. STUDY: Using the Business Objects database of
Clalit Health Services in the Tel Aviv district we identified all patients over
18 years-old with a diagnosis of ulcerative colitis (UC) on 31.12.05. This cohort
was followed until 31.12.12. Subjects over age 50 without IBD who are also
targeted for influenza vaccination served as controls. The uptake of annual
influenza vaccination was recorded. RESULTS: 470 UC patients were included (241
(51.3%) males, age 50.4 +/- 18.4 years, disease duration 158.9 +/- 86.5 months),
and 2960 controls. During the years 2006, 2007, 2008, 2009, 2010, 2011 and 2012
the uptake of influenza vaccination was 101 (21.5%), 122 (26.0%), 147 (31.3%),
181 (38.5%), 177 (37.7%), 170 (36.2%) and 178 (37.9%) amongst UC patients, and
993 (33.5%), 1360 (45.9%), 1524 (51.5%), 1611 (54.4%), 1446 (48.9%), 1576 (53.2%)
and 1557 (52.6%) amongst controls (p<0.0001 for every year). Independent
predictors of vaccination included age (OR, 1.05; 95% CI, 1.03-1.06; p<0.001) and
cardiovascular risk (OR, 1.81; 95% CI, 1.31-2.49; p<0.01). CONCLUSIONS: Although
uptake influenza vaccination is consistently lower in UC compared to controls, an
upward trend was observed over the study period. Public health initiatives should
target this high-risk population to promote immunization.
PMID- 25132338
TI - Curcumin attenuates cardiac fibrosis in spontaneously hypertensive rats through
PPAR-gamma activation.
AB - AIM: To investigate the effects of curcumin (Cur) on cardiac fibrosis in
spontaneously hypertensive rats (SHRs) and the mechanisms underlying the anti
fibrotic effect of Cur in rat cardiac fibroblasts (CFs) in vitro. METHODS: SHRs
were orally treated with Cur (100 mg.kg(-1).d(-1)) or Cur (100 mg.kg(-1).d(-1))
plus the PPAR-gamma antagonist GW9662 (1 mg.kg(-1).d(-1)) for 12 weeks. Cultured
CFs were treated with angiotensin II (Ang II, 0.1 MUmol/L) in vitro. The
expression of relevant proteins and mRNAs was analyzed using Western blotting and
real-time PCR, respectively. The expression and activity of peroxisome
proliferator-activated receptor-gamma (PPAR-gamma) were detected using Western
blotting and a DNA-binding assay, respectively. RESULTS: Treatment of SHRs with
Cur significantly decreased systolic blood pressure, blood Ang II concentration,
heart weight/body weight ratio and left ventricle weight/body weight ratio, with
concurrently decreased expression of connective tissue growth factor (CTGF),
plasminogen activator inhibitor (PAI)-1, collagen III (Col III) and fibronectin
(FN), and increased expression and activity of PPAR-gamma in the left ventricle.
Co-treatment with GW9662 partially abrogated the anti-fibrotic effects of Cur in
SHRs. Pretreatment of CFs with Cur (5, 10, 20 MUmol/L) dose-dependently inhibited
Ang II-induced expression of CTGF, PAI-1, Col III and FN, and increased the
expression and binding activity of PPAR-gamma. Pretreatment with GW9662 partially
reversed anti-fibrotic effects of Cur in vitro. Furthermore, pretreatment of CFs
with Cur inhibited Ang II-induced expression of transforming growth factor-beta1
(TGF-beta1) and phosphorylation of Smad2/3, which were reversed by GW9662.
CONCLUSION: Cur attenuates cardiac fibrosis in SHRs and inhibits Ang II-induced
production of CTGF, PAI-1 and ECM in CFs in vitro. The crosstalk between PPAR
gamma and TGF-beta1/Smad2/3 signaling is involved in the anti-fibrotic and anti
proliferative effects of Cur.
PMID- 25132339
TI - Crotoxin induces apoptosis and autophagy in human lung carcinoma cells in vitro
via activation of the p38MAPK signaling pathway.
AB - AIM: Crotoxin (CrTX) is the primary toxin in South American rattlesnake (Crotalus
durissus terrificus) venom, and exhibits antitumor and other pharmacological
actions in vivo and in vitro. Here, we investigated the molecular mechanisms of
the antitumor action of CrTX in human lung carcinoma cells in vitro. METHODS:
Human lung squamous carcinoma SK-MES-1 cells were tested. The cytotoxicity of
CrTX was evaluated in both MTT and colony formation assays. Cell cycle was
investigated with flow cytometry. Cell apoptosis was studied with Hoechst 33258
and Annexin V-FITC staining. The levels of relevant proteins were analyzed using
Western blot assays. RESULTS: CrTX (25, 50, 100 MUmol/L) inhibited the growth and
colony formation of SK-MES-1 cells in dose- and time-dependent manners. CrTX
increased the proportion of S phase cells and dose-dependently induced cell
apoptosis, accompanied by down-regulating the expression of proliferating cell
nuclear antigen (PCNA), and increasing the level of cleaved caspase-3.
Furthermore, CrTX dose-dependently increased the expression of autophagy-related
proteins LC3-II and beclin 1, and decreased the level of p62 in the cells.
Moreover, CrTX (50 MUmol/L) significantly increased p38MAPK phosphorylation in
the cells. Pretreatment of the cells with SB203580, a specific inhibitor of
p38MAPK, blocked the inhibition of CrTX on cell proliferation, as well as CrTX
induced apoptosis and cleaved caspase-3 expression. CONCLUSION: The p38MAPK
signaling pathway mediates CrTX-induced apoptosis and autophagy of human lung
carcinoma SK-MES-1 cells in vitro.
PMID- 25132341
TI - Leaf-shape remodeling: programmed cell death in fistular leaves of Allium
fistulosum.
AB - Some species of Allium in Liliaceae have fistular leaves. The fistular lamina of
Allium fistulosum undergoes a process from solid to hollow during development.
The aims were to reveal the process of fistular leaf formation involved in
programmed cell death (PCD) and to compare the cytological events in the
execution of cell death to those in the unusual leaf perforations or plant
aerenchyma formation. In this study, light and transmission electron microscopy
were used to characterize the development of fistular leaves and cytological
events. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling
(TUNEL) assays and gel electrophoresis were used to determine nuclear DNA
cleavage during the PCD. The cavity arises in the leaf blade by degradation of
specialized cells, the designated pre-cavity cells, in the center of the leaves.
Nuclei of cells within the pre-cavity site become TUNEL-positive, indicating that
DNA cleavage is an early event. Gel electrophoresis revealed that DNA
internucleosomal cleavage occurred resulting in a characteristic DNA ladder.
Ultrastructural analysis of cells at the different stages showed disrupted
vacuoles, misshapen nuclei with condensed chromatin, degraded cytoplasm and
organelles and emergence of secondary vacuoles. The cell walls degraded last, and
residue of degraded cell walls aggregated together. These results revealed that
PCD plays a critical role in the development of A. fistulosum fistular leaves.
The continuous cavity in A. fistulosum leaves resemble the aerenchyma in the pith
of some gramineous plants to improve gas exchange.
PMID- 25132340
TI - Protocol for a prospective magnetic resonance imaging study on supraspinal lower
urinary tract control in healthy subjects and spinal cord injury patients
undergoing intradetrusor onabotulinumtoxinA injections for treating neurogenic
detrusor overactivity.
AB - BACKGROUND: The control of the lower urinary tract is a complex, multilevel
process involving both the peripheral and central nervous system. Due to lesions
of the neuraxis, most spinal cord injury patients suffer from neurogenic lower
urinary tract dysfunction, which may jeopardise upper urinary tract function and
has a negative impact on health-related quality of life. However, the alterations
to the nervous system following spinal cord injury causing neurogenic lower
urinary tract dysfunction and potential effects of treatments such as
intradetrusor onabotulinumtoxinA injections on lower urinary tract control are
poorly understood. METHODS/DESIGN: This is a prospective structural and
functional magnetic resonance imaging study investigating the supraspinal lower
urinary tract control in healthy subjects and spinal cord injury patients
undergoing intradetrusor onabotulinumtoxinA injections for treating neurogenic
detrusor overactivity.Neuroimaging data will include structural magnetic
resonance imaging (T1-weighted imaging and diffusion tensor imaging) as well as
functional, i.e. blood oxygen level-dependent sensitive magnetic resonance
imaging using a 3 T magnetic resonance scanner. The functional magnetic resonance
imaging will be performed simultaneously to three different bladder stimulation
paradigms using an automated magnetic resonance compatible and synchronised pump
system.All subjects will undergo two consecutive and identical magnetic resonance
imaging measurements. Healthy subjects will not undergo any intervention between
measurements but spinal cord injury patients will receive intradetrusor
onabotulinumtoxinA injections for treating neurogenic detrusor
overactivity.Parameters of the clinical assessment including bladder diary,
urinalysis, medical history, neuro-urological examination, urodynamic
investigation as well as standardised questionnaires regarding lower urinary
tract function and quality of life will serve as co-variates in the magnetic
resonance imaging analysis. DISCUSSION: This study will identify structural and
functional alterations in supraspinal networks of lower urinary tract control in
spinal cord injury patients with neurogenic detrusor overactivity compared to
healthy controls. Post-treatment magnetic resonance imaging measurements in
spinal cord injury patients will provide further insights into the mechanism of
action of treatments such as intradetrusor onabotulinumtoxinA injections and the
effect on supraspinal lower urinary tract control. TRIAL REGISTRATION:
ClinicalTrials.gov NCT01768910.
PMID- 25132342
TI - Hippocampal NMDA receptors and the previous experience effect on memory.
AB - N-methyl-D-aspartate receptors (NMDAR) are thought to be responsible for
switching synaptic activity specific patterns into long-term changes in synaptic
function and structure, which would support learning and memory. Hippocampal
NMDAR blockade impairs memory consolidation in rodents, while NMDAR stimulation
improves it. Adult rats that explored twice an open field (OF) before a weak
though overthreshold training in inhibitory avoidance (IA), expressed IA long
term memory in spite of the hippocampal administration of MK-801, which currently
leads to amnesia. Those processes would involve different NMDARs. The selective
blockade of hippocampal GluN2B-containing NMDAR with ifenprodil after training
promoted memory in an IA task when the training was weak, suggesting that this
receptor negatively modulates consolidation. In vivo, after 1h of an OF exposure
with habituation to the environment-, there was an increase in GluN1 and GluN2A
subunits in the rat hippocampus, without significant changes in GluN2B.
Coincidentally, in vitro, in both rat hippocampal slices and neuron cultures
there was an increase in GluN2A-NMDARs surface expression at 30min; an increase
in GluN1 and GluN2A levels at about 1h after LTP induction was also shown. We
hypothesize that those changes in NMDAR composition could be involved in the
"anti-amnesic effect" of the previous OF. Along certain time interval, an
increase in GluN1 and GluN2A would lead to an increase in synaptic NMDARs,
facilitating synaptic plasticity and memory; while then, an increase in
GluN2A/GluN2B ratio could protect the synapse and the already established
plasticity, perhaps saving the specific trace.
PMID- 25132343
TI - Expression of placenta growth factor, soluble fms-like tyrosine kinase-1, metal
responsive transcription factor-1, heme oxygenase 1 and hypoxia inducible factor
1alpha mRNAs in pre-eclampsia placenta and the effect of pre-eclampsia sera on
their expression of choriocarcinoma cells.
AB - AIM: We studied the effect of pre-eclampsia sera on the expression of placenta
growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), metal
responsive transcription factor-1 (MTF-1), heme oxygenase 1 (HO-1) and hypoxia
inducible factor-1alpha (HIF-1alpha) mRNAs in JEG-3 cells (trophoblast-derived
cells) and placenta from pre-eclampsia patients to investigate pre-eclampsia
pathophysiology. MATERIAL AND METHODS: Placenta and serum samples were taken from
pre-eclampsia and normal pregnancy patients. JEG-3 cells were cultured with pre
eclampsia and normal pregnant sera in 24-well tissue culture plates. RNA was
purified from placental trophoblast cells and JEG-3 cells 24 h after incubation.
The expression of mRNA was measured using real-time polymerase chain reaction.
RESULTS: The expression of sFlt-1 mRNA increased, and that of PlGF and HO-1 mRNA
decreased in JEG-3 cells after incubation with pre-eclampsia sera. The expression
of PlGF mRNA decreased, and that of sFlt-1mRNA increased in pre-eclampsia
placenta. The expression of MTF-1 and HO-1 mRNA decreased. A correlation was
found between PlGF mRNA expression and the expression of MTF-1 and HIF-1alpha
mRNA. A correlation between sFlt-1 and HIF-1alpha mRNA expression was also found.
CONCLUSION: Changes in PlGF mRNA expression in pre-eclampsia placenta may relate
to serum factors and the expression of MTF-1 and HIF-alpha mRNA. Changes in sFlt
1mRNA expression may relate to serum factors and the expression of HIF-alpha
mRNA. We suggest that serum factors play a role in PlGF and sFlt-1 expression in
pre-eclampsia placenta.
PMID- 25132344
TI - Inflammatory features of melasma lesions in Asian skin.
AB - Melasma is triggered by various factors including ultraviolet radiation and
estrogen; however, its pathogenesis is unclear. To investigate the inflammatory
features of melasma lesions as triggers for this disorder, 197 women with melasma
who attended Asan Medical Center and Kangskin Clinic, Seoul, from June 2011 to
October 2011 completed a questionnaire concerning triggering or aggravating
factors. These cases were divided into "non-inflammatory" and "inflammatory"
groups. Skin biopsies and immunostaining for CD68, CD117, and leukocyte common
antigen (LCA) were performed in the lesional and peri-lesional skin of ten cases
in the non-inflammatory group and nine cases in the inflammatory group. Among the
197 subjects (mean age, 41.5 years; mean age of melasma onset, 33.8 years), 50
patients (25.4%) were categorized into the inflammatory group. This group
comprised cases that had inflammatory symptoms and events that triggered the
melasma lesions. The lesional dermis contained more CD68(+) melanophages,
CD117(+) mast cells, and LCA(+) leukocytes in the inflammatory group than in the
non-inflammatory group. Inflammatory clinical features and an increased number of
inflammatory cells in the lesion may be involved in the development of melasma in
Asian skin.
PMID- 25132346
TI - Pain at the game: spontaneous coronary artery dissection.
PMID- 25132347
TI - Neither here nor there: impending paradoxical embolism.
PMID- 25132348
TI - Ramsay Hunt syndrome presenting with ataxia and syndrome of inappropriate
antidiuretic hormone secretion.
PMID- 25132345
TI - Laminar and neurochemical organization of the dorsal cochlear nucleus of the
human, monkey, cat, and rodents.
AB - The dorsal cochlear nucleus (DCN) is a brainstem structure that receives input
from the auditory nerve. Many studies in a diversity of species have shown that
the DCN has a laminar organization and identifiable neuron types with predictable
synaptic relations to each other. In contrast, studies on the human DCN have
found a less distinct laminar organization and fewer cell types, although there
has been disagreement among studies in how to characterize laminar organization
and which of the cell types identified in other animals are also present in
humans. We have reexamined DCN organization in the human using
immunohistochemistry to analyze the expression of several proteins that have been
useful in delineating the neurochemical organization of other brainstem
structures in humans: nonphosphorylated neurofilament protein (NPNFP), nitric
oxide synthase (nNOS), and three calcium-binding proteins. The results for humans
suggest a laminar organization with only two layers, and the presence of large
projection neurons that are enriched in NPNFP. We did not observe evidence in
humans of the inhibitory interneurons that have been described in the cat and
rodent DCN. To compare humans and other animals directly we used
immunohistochemistry to examine the DCN in the macaque monkey, the cat, and three
rodents. We found similarities between macaque monkey and human in the expression
of NPNFP and nNOS, and unexpected differences among species in the patterns of
expression of the calcium-binding proteins.
PMID- 25132349
TI - Left upper pulmonary vein thrombus in a patient with atrial fibrillation and
prior lobectomy.
PMID- 25132350
TI - Urinary creatinine-splitting bacteria after ileal-loop diversion causing
underestimate of glomerular filtration rate.
PMID- 25132351
TI - What's in a word? Using words carefully.
PMID- 25132352
TI - The fastest way to make an enemy.
PMID- 25132353
TI - The importance and role of clinical imaging guidelines: the example of the ACR
Appropriateness Criteria((r)) on Renal Failure.
PMID- 25132354
TI - Osteopontin deficiency does not prevent but promotes alcoholic neutrophilic
hepatitis in mice.
AB - Alcoholic hepatitis (AH) is a distinct spectrum of alcoholic liver disease (ALD)
with intense neutrophilic (polymorphonuclear; PMN) inflammation and high
mortality. Although a recent study implicates osteopontin (SPP1) in AH, SPP1 is
also shown to have protective effects on experimental ALD. To address this
unsettled question, we examined the effects of SPP1 deficiency in male mice given
40% calories derived from ad libitum consumption of the Western diet high in
cholesterol and saturated fat and the rest from intragastric feeding of alcohol
diet without or with weekly alcohol binge. Weekly binge in this new hybrid
feeding model shifts chronic ASH with macrophage inflammation and perisinusoidal
and pericellular fibrosis to AH in 57% (15 of 26) of mice, accompanied by
inductions of chemokines (Spp1, Cxcl1, and interleukin [Il]-17a), progenitor
genes (Cd133, Cd24, Nanog, and epithelial cell adhesion molecule), PMN
infiltration, and clinical features of AH, such as hypoalbuminemia,
bilirubinemia, and splenomegaly. SPP1 deficiency does not reduce AH incidence and
inductions of progenitor and fibrogenic genes, but rather enhances the Il-17a
induction and PMN infiltration in some mice. Furthermore, in the absence of SPP1,
chronic ASH mice without weekly binge begin to develop AH. CONCLUSION: These
results suggest that SPP1 has a protective, rather than causal, role for
experimental AH reproduced in our model.
PMID- 25132356
TI - What is in a name? Nonfinancial influences on the outcomes of systematic reviews
and guidelines.
PMID- 25132357
TI - Judging pathological assessment in cancer specimens.
AB - The pathologist plays a critical role in the multidisciplinary team in charge of
treating cancer patients, as many of the therapeutic decisions rely on the
information conveyed through the pathology reports. The task of the pathologist
includes not only an accurate assessment of pathological T and N categories, but
also the evaluation of other indicators of prognosis including quality of
surgery, margins of resection, as well as additional histopathological and
molecular markers that influence prognosis and could predict response to therapy.
PMID- 25132355
TI - Differential cellular expression of organic anion transporting peptides OATP1A2
and OATP2B1 in the human retina and brain: implications for carrier-mediated
transport of neuropeptides and neurosteriods in the CNS.
AB - Organic anion transporting polypeptides (OATPs) are polyspecific organic anion
transporters, which are expressed in the blood-brain barrier, the choroid plexus,
and other organs. The physiologic function of OATPs in extrahepatic tissues
remains ambiguous. In rat retina, members of the OATP family are expressed. We
therefore investigated the human retina for the expression of OATP1A2 and OATP2B1
and extended the study to human brain. Furthermore, we searched for peptide
neurotransmitters as novel OATP substrates. OATP1A2 displayed a broad expression
pattern in human retina as assessed by immunofluorescence localization. It is
expressed in photoreceptor bodies and somas of amacrine cells. OATP1B2 expression
is restricted to the inner nuclear layer and to the inner plexiform layer. Using
paraffin sections from human cortex, cerebellum, and hippocampus, OATP1A2 was
localized to neurons and neuronal processes, while OATP2B1 is expressed in
endothelial cells of brain capillaries. Substance P and vasoactive intestinal
peptide were identified as substrates for OATP1A2 and OATP2B1. Double-labeling
immunofluorescence of human retina demonstrated the presence of substance P and
of vasoactive intestinal peptides in neurons expressing OATP1A2 and OATP2B1,
respectively. The expression of OATP1A2 and OATP2B1 in retinal neurons implies a
role of these transporters in the reuptake of peptide neurotransmitters released
from retinal neurons. The abundant expression of OATP1A2 in brain neurons points
to the possibility that OATP1A2 could be involved in the homeostasis of
neurosteroids. The high expression of OATP2B1 in brain capillaries supports an
important function of OATPs in substance penetration across the blood-brain
barrier.
PMID- 25132358
TI - phylin: an r package for phylogeographic interpolation.
AB - phylin is a package for the r programming environment which offers different
methods to spatially interpolate genetic information from phylogeographic data.
These interpolations can be used to predict the spatial occurrence of different
lineages within a phylogeny using a modified method of kriging, which allows the
usage of a genetic distance matrix to derive a model of spatial dependence.
phylin improves the available methods to generate interpolated surfaces from a
phylogenetic trees by assessing the autocorrelation structure of the genetic
information, interpolating the genetic data based on a statistical model,
estimating the uncertainty of the predictions and identifying lineage occurrence
and contact zones probability without projection of pairwise genetic distances
into mid-points between sample locations. The package also includes methods to
plot interpolation surfaces and provide summary tables from the generated data
and models. We provide an example of the usefulness of this tool by inferring the
spatial occurrence of distinct historical evolutionary lineages of the Lataste's
viper (Vipera latastei Bosca, 1878) in the Iberian Peninsula and identifying
potential contact areas. The maps of phylogenetic patterns obtained with these
methods provide a spatial context to test hypotheses related to processes
underlying the geographic distribution of genetic diversity and to inform
conservation planning.
PMID- 25132359
TI - Cancer research in France.
PMID- 25132360
TI - Exercise decreases speedball self-administration.
AB - AIMS: Epidemiological studies report that individuals who exercise are less
likely to abuse drugs. Preclinical studies report that exercise, in the form of
treadmill or wheel running, reliably decreases the self-administration of
psychomotor stimulants and opioids. To date, preclinical studies have only
examined the effects of exercise on responding maintained by individual drugs and
not by combinations of multiple drugs. This limits the translational appeal of
these studies because polydrug abuse is common among substance abusing
populations. The purpose of this study was to examine the effects of exercise on
the self-administration of speedball, a combination of cocaine and heroin that is
frequently encountered in intravenous drug abusing populations. MAIN METHODS:
Female rats were obtained at weaning and assigned to sedentary or exercising
conditions. Sedentary rats were housed in standard cages that permitted no
exercise beyond normal cage ambulation; exercising rats were housed in similar
cages with an activity wheel. After 6weeks, rats were implanted with intravenous
catheters and trained to self-administer cocaine, heroin, and dose combinations
of cocaine and heroin (i.e., speedball) on a progressive ratio schedule of
reinforcement. KEY FINDINGS: Doses of speedball maintained greater levels of
responding than corresponding doses of cocaine and heroin alone. Importantly,
responding maintained by cocaine, heroin, and speedball was lower in exercising
rats than sedentary rats. SIGNIFICANCE: These data indicate that exercise
decreases the self-administration of speedball and suggest that exercise may
reduce the abuse of drug combinations that have traditionally been resistant to
treatment.
PMID- 25132361
TI - Gastrodin prevents motor deficits and oxidative stress in the MPTP mouse model of
Parkinson's disease: involvement of ERK1/2-Nrf2 signaling pathway.
AB - AIMS: Current no effective therapy is available to halt the progression of
Parkinson's disease (PD). Oxidative stress has been implicated in the etiology of
PD. The present study evaluates the hypothesis that prevention of 1-methyl-4
phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor deficits by gastrodin
might mainly result from its antioxidant property via interrupting extracellular
signal regulated protein kinases (ERK) 1/2-nuclear factor erythroid 2-related
factor 2 (Nrf2) signaling pathway. MAIN METHODS: Pretreatment of mouse model of
PD is established by treating C57BL/6 mice with 4 doses of MPTP (30 mg/kg per
day, i.p.), with gastrodin (60 mg/kg per day) administered by daily
intraperitoneal injection for 2 weeks. Motor behavior of mice was monitored by
open-field test and rotarod test. Real-time polymerase chain reaction and Western
blotting were used to analyze the expression of genes. KEY FINDINGS: MPTP-induced
motor deficits were partially and significantly forestalled by gastrodin.
Gastrodin treatment prevented MPTP-induced oxidative stress, as measured by
malondialdehyde in midbrain. Interestingly, MPTP-intoxicated mice treated with
gastrodin robustly increased heme oxygenase 1, superoxide dismutase, glutathione
levels, and Nrf2 nuclear translocation in striatum of MPTP-intoxicated mice.
Furthermore, results herein suggest that the antioxidant pathway activated by
gastrodin involves ERK1/2 phosphorylation. SIGNIFICANCE: Gastrodin protects
midbrain of MPTP-intoxicated mice against oxidative stress, in part, through
interrupting ERK1/2-Nrf2 pathway mechanism, which will give us an insight into
the potential of gastrodin in terms of opening up new therapeutic avenues for PD.
PMID- 25132362
TI - Animal models of social anxiety disorder and their validity criteria.
AB - Anxiety disorders pose one of the largest threats to global mental health, and
they predominantly emerge early in life. Social anxiety disorder, also known as
social phobia, is the most common of all anxiety disorders. Moreover, it has
severe consequences and is a disabling disorder that can cause an individual to
be unable to perform the tasks of daily life. Social anxiety disorder is
associated with the subsequent development of major depression and other mental
diseases, as well as increased substance abuse. Although some neurobiological
alterations have been found to be associated with social anxiety disorder, little
is known about this disorder. Animal models are useful tools for the
investigation of this disorder, as well as for finding new pharmacological
targets for treatment. Thus, this review will highlight the main animal models of
anxiety associated with social phobia.
PMID- 25132363
TI - The flavan-3-ol fraction of cocoa powder suppressed changes associated with early
stage metabolic syndrome in high-fat diet-fed rats.
AB - AIMS: Previous epidemiological studies have suggested that ingestion of chocolate
reduces the risk of cardiovascular disease. In the present study, we examined the
effects of flavan-3-ols derived from cocoa on blood pressure, lipolysis, and
thermogenesis in rats fed a high-fat diet and that showed early signs of
metabolic syndrome. MAIN METHODS: The rats were divided into three groups, and
fed either normal diet (normal), 60% fat high-fat diet (HFD), or HFD containing
0.2% flavan-3-ols (HFD-flavan) for 4 weeks. At the end of the feeding period,
blood pressure was measured and animals were sacrificed under anesthesia.
Lipolysis and thermogenesis-related protein levels were measured in several
tissues by Western blotting, and mitochondrial DNA copy number was measured by RT
PCR. KEY FINDINGS: Mean blood pressure and epididymal adipose tissue weight of
HFD-flavan were significantly lower compared with those of HFD. Uncoupling
protein (UCP)1 in brown adipose tissue and UCP3 in gastrocnemius of HFD-flavan
were significantly increased compared with those of HFD group. Carnitine
palmitoyltransferase (CPT) 2 levels in liver and medium-chain acyl-CoA
dehydrogenase (MCAD) levels in gastrocnemius and liver were significantly
increased by the supplementation of flavan-3-ols. SIGNIFICANCE: In addition to
having hypotensive effects, flavan-3-ols enhance thermogenesis and lipolysis and
consequently reduce white adipose tissue weight gain in response to high-fat diet
feeding.
PMID- 25132364
TI - In-office bleaching gel with 35% hydrogen peroxide enhanced biofilm formation of
early colonizing streptococci on human enamel.
AB - OBJECTIVES: To compare the effects of 25% and 35% hydrogen peroxide in-office
bleaching systems on surface roughness and streptococcal biofilm formation on
human enamel. METHODS: Enamel specimens (3mm*3mm*2mm, n=162) from human permanent
teeth were randomly divided into 3 treatment groups (n=54 each): (1) control, (2)
bleached with 25% hydrogen peroxide (Zoom2TM), and (3) bleached with 35% hydrogen
peroxide (BeyondTM). The enamel surface roughness was measured by a profilometer
before and after treatments. Subsequently, the treated enamel specimens were
randomly placed into 3 subgroups (n=18 each) and incubated with: (1) trypticase
soy broth control, (2) Streptococcus mutans culture and (3) Streptococcus
sanguinis culture for 24h. Biofilm formation was quantified by crystal violet
staining. The biofilm structure on three specimens from each group was visualized
by scanning electron microscopy. Data were analyzed by Kruskal-Wallis and Mann
Whitney U tests with Bonferroni corrections. Significance level was set at
p<0.05. RESULTS: Both bleaching systems significantly reduced enamel surface
roughness comparing to the control group (p<0.001), but there was no difference
between the two treatment groups. Remarkably, S. sanguinis biofilm formation was
significantly higher on enamel specimens bleached with 35% hydrogen peroxide than
other treatments (p<0.001), but was lower on those bleached with 25% hydrogen
peroxide (p<0.001). In contrast, no difference in S. mutans biofilm formation was
observed among the three treatment groups. CONCLUSION: Both 25% and 35% hydrogen
peroxide caused similar degrees of reduction in enamel surface roughness.
Nevertheless, bleaching with 35% hydrogen peroxide appeared to markedly promote
S. sanguinis biofilm formation. CLINICAL SIGNIFICANCE: The increase of early
colonizer biofilm raised concerns over adverse effects of in-office bleaching on
plaque formation. This should be further investigated in vivo and efficient
plaque control should be emphasized after bleaching with high concentrations of
hydrogen peroxide.
PMID- 25132365
TI - The strength of sintered and adhesively bonded zirconia/veneer-ceramic bilayers.
AB - OBJECTIVES: Recently all-ceramic restorative systems have been introduced that
use CAD/CAM technology to fabricate both the Y-TZP core and veneer-ceramic
layers. The aim was to identify whether the CAD/CAM approach resulted in more
favourable stressing patterns in the veneer-ceramic when compared with a
conventionally sintered Y-TZP core/veneer-ceramic. METHODS: Nominally identical
Vita VM9 veneer-ceramic disc-shaped specimens (0.7mm thickness, 12mm diameter)
were fabricated. 20 specimens received a surface coating of resin-cement (Panavia
21); 20 specimens were bonded with the resin-cement to fully sintered Y-TZP (YZ
Vita Inceram Vita) discs (0.27mm thickness, 12mm diameter). A final series of 20
Y-TZP core/veneer-ceramic specimens were manufactured using a conventional
sintering route. Biaxial flexure strength was determined in a ball-on-ring
configuration and stress at the fracture origin calculated using multilayer
closed-form analytical solutions. Fractography was undertaken using scanning
electron microscopy. The experimental test was simulated using Finite Element
Analysis. Group mean BFS were compared using a one-way ANOVA and post hoc Tukey
tests at a 95% significance level. RESULTS: Resin cement application resulted in
significant strengthening of the veneer-ceramic and further significant
strengthening of the veneer-ceramic (p<0.01) occurred following bonding to the Y
TZP core. The BFS calculated at the failure origin for conventionally sintered
specimens was significantly reduced when compared with the adhesively bonded Y
TZP/veneer-ceramic. CONCLUSIONS: Under the test conditions employed adhesive
cementation between CAD/CAM produced Y-TZP/veneer-ceramic layers appears to offer
the potential to induce more favourable stress states within the veneer-ceramic
when compared with conventional sintered manufacturing routes. CLINICAL
SIGNIFICANCE: The current investigation suggests that the stressing patterns that
arise in all-ceramic restorations fabricated using CAD/CAM for both the core and
veneer-ceramic layers differ from those that occur in conventionally sintered
bilayer restorations. Further work is required to ascertain whether such
differences will translate into improved clinical outcomes.
PMID- 25132366
TI - Effect of temperature on post-cure polymerization of bulk-fill composites.
AB - OBJECTIVES: To investigate the 24h post-cure polymerization and the effect of
temperature on the post-cure polymerization of one conventional and three bulk
fill composite materials. METHODS: A conventional composite GrandioSO (GR) and
three bulk-fill composites: Tetric EvoCeram Bulk Fill (TECBF), Quixfil (QF) and X
tra fil (XF) were investigated. The samples were cured for 20s with irradiance of
1090mW/cm(2). Composite samples were divided into two groups: the "room
temperature" group (RT, n=5) and the "body-temperature" group (BT, n=5) and they
were stored in dark at 20 degrees C and 37 degrees C, respectively. Measurements
of degree of conversion (DC) were made immediately after curing (0h) and 24h post
cure (24h). To analyse the extent of post-cure DC increase, the DC values of 0h
RT/24h-RT and 0h-BT/24h-BT were compared. To analyse the difference in DC between
RT and BT, the DC values of 0h-RT/0h-BT and 24h-RT/24h-BT were compared. RESULTS:
DC increase 24h post-cure was significant for all composites and ranged between
6.3% and 8.2% in RT and between 12.5% and 15.7% in BT. All composites
demonstrated a higher DC in 24h-BT compared to 24h-RT. The difference was
statistically significant for GR, TECBF and QF. CONCLUSIONS: All composites
demonstrated a significant post-cure effect after 24h. Post-cure temperature
increase from 20 degrees C to 37 degrees C yielded a higher post-cure DC
increase. CLINICAL SIGNIFICANCE: Due to the temperature effect on the final DC,
studies performed at composite samples at room temperature may record more
inferior properties than these attained in the oral cavity.
PMID- 25132368
TI - Salivary gland carcinomas in children and adolescents: the Italian TREP project
experience.
AB - BACKGROUND: Salivary gland carcinomas are extremely rare in pediatric age. We
report the clinical features of a series of children/adolescents with salivary
gland carcinomas prospectively registered in the Italian TREP (Rare Tumors in
Pediatric Age) project. PROCEDURES: Diagnostic/therapeutic guidelines were
developed and shared among Italian pediatric oncology/surgical centers. RESULTS:
Seventeen patients were registered between 2000 and 2012, representing 19% of the
cases expected to be seen based on epidemiological data. Tumors arose mainly in
the parotid gland (14 cases). In most cases they were low-grade tumors (14
cases), often with a favorable clinical presentation, and low-stage disease. All
patients underwent surgical resection, achieving histologically free margins in
9/17 cases. Thirteen of the 14 patients with parotid gland tumors had
parotidectomy (10 total, 3 superficial), while one had a tumorectomy.
Postoperative facial nerve lesions were reported in two cases. Adjuvant
radiotherapy was given to 6 patients. The overall prognosis was good: only one
patient with a huge high-grade tumor experienced disease progression and died of
the disease. The other 16 patients were alive in first continuous remission 1-8
years after diagnosis. In 4/17 cases, the salivary gland carcinoma was a second
tumor occurring 6-9 years after another primary cancer. CONCLUSIONS: This is the
first reported prospective national cooperative series of pediatric salivary
gland carcinoma patients. Compliance with the TREP recommendations was high.
These tumors are rarely managed by pediatric oncologists/surgeons. A broader
international cooperation and better networking with otolaryngologists and head
neck surgeons expert on adult salivary gland carcinomas would be advisable.
PMID- 25132367
TI - Marginal integrity and secondary caries of selectively excavated teeth in vitro.
AB - OBJECTIVES: Selective caries removal involves sealing of carious dentine beneath
restorations, which might decrease their marginal integrity and increase the
susceptibility for secondary caries and microleakage. The present study compared
these marginal characteristics of restorations in selectively and completely
excavated teeth. METHODS: In 32 premolars, shallow and deep artificial lesions
were created on pulpo-axial walls of mesial-distal-occlusal cavities, with mesial
and distal margins located in enamel and dentine, respectively. Demineralised
dentine was either removed or left before adhesively restoring the teeth (n=8),
which were then submitted to thermo-mechanical cycling. The integrity of gingivo
cervical margins was assessed using scanning electron microscopy. In half of each
margin, caries was induced adjacent to restorations using a continuous-culture
biofilm model, and resulting lesions were evaluated using transversal
microradiography. The other half of each margin was used to assess microleakage.
RESULTS: Integrity or microleakage of margins located in enamel did not differ
significantly between groups, and bacterial biofilms did not induce distinct
caries lesions in enamel. Dentinal margins in teeth with deep compared with
shallow lesions showed a significantly higher proportion of marginal
imperfections, gaps and microleakage (p<=0.05, Mann-Whitney/chi(2)-test). In
contrast, neither marginal integrity nor microleakage differed significantly
between completely and selectively excavated teeth (p>0.05). Dentinal mineral
loss adjacent to restorations did not differ significantly between groups
(p>0.80). CONCLUSIONS: The marginal characteristics of restorations were affected
by the depth of sealed or excavated lesions, but not by the performed caries
excavation. This study did not find selective excavation detrimental for
restoration integrity in vitro. CLINICAL SIGNIFICANCE: Selective excavation of
deep lesions was shown to reduce pulpal risks, whilst leaving caries beneath
restorations is feared to compromise the marginal characteristics of the
subsequently placed restoration. Based on the present in vitro study, such
assumptions cannot be supported.
PMID- 25132369
TI - Proton and deuterium nuclear spin relaxation study of the SmA and SmC* phases of
BP8Cl-d17 : a self-consistent analysis.
AB - A self-consistent analysis of proton and deuterium nuclear spin relaxation times
in the smectic phases of a partially deuterated smectogen is presented here.
Proton spin-lattice relaxation times T(1Z) were measured as a function of Larmor
frequency over a range of 1 kHz to 300 MHz at selected temperatures. Deuterium
spin relaxation times T(1Z) and T(1Q) were measured as a function of temperature
at two different magnetic fields in the smectic A phase. The deuterium data
provide dynamic parameters such as rotational diffusion constants and internal
jump rates as well as the nematic order parameter S. The proton data are analyzed
using a number of relaxation mechanisms, one of which is the molecular
reorientation. It is found helpful in these latter analyses to use the nematic
order parameter and to fix the contribution from molecular reorientations
determined by the deuterium spin relaxation. The fits to the proton T(1)
frequency and temperature dispersions by the remaining relaxation mechanisms such
as layer undulations and translational self-diffusion will be discussed for the
smectic A and chiral smectic C phases.
PMID- 25132370
TI - Clinical phenotype and genetic analysis of RPS19, RPL5, and RPL11 genes in Greek
patients with Diamond Blackfan Anemia.
AB - BACKGROUND: Diamond Blackfan Anemia (DBA) is a rare congenital, bone marrow
failure syndrome characterized by normochromic macrocytic anemia,
reticulocytopenia and absence or insufficiency of erythroid precursors in
normocellular bone marrow, frequently associated with somatic malformations.
Here, we present our findings from the study of 17 patients recorded in the Greek
DBA registry. PROCEDURE: Clinical evaluation of patients and data collection was
performed followed by the molecular analysis of RPS19, RPL5, and RPL11 genes.
Mutation screening included PCR amplification, ECMA analysis, and direct
sequencing. RESULTS: Congenital anomalies were observed in 71% of the patients.
Six patients (35.2%) were found to carry mutations on either the RPS19 gene
(three patients,) or the RPL5 gene (three patients). Mutations c.C390G (p.Y130X)
and c.197_198insA (p.Y66X) detected in the RPL5 gene were novel. No mutations at
the RPL11 gene were identified in Greek patients with DBA. CONCLUSIONS: The
clinical course of the patients was similar to previous reports. The occurrence
of thyroid carcinoma in an adult patient with DBA is the first to be reported in
DBA.
PMID- 25132371
TI - Non-disclosure of widowhood in Nepal: implications for women and their children.
AB - Non-disclosure of significant or emotionally charged information can have
psychological and physical health consequences. Widowhood in Nepal is highly
stigmatised and therefore is a sensitive topic. This study sought to understand
why and to whom women do not disclose their status as widows. Thematic content
analysis of 31 in-depth interviews and 6 focus groups was conducted with
primarily high-caste widows of reproductive age from the Kathmandu Valley,
Surkhet, Chitwan and Kavre districts of Nepal. A codebook was developed based
upon recurring concepts and applied to all transcripts using Atlas.ti. Due to
discomfort or stigmatisation, many women concealed their status as widows in the
community through behaviours impacting their daily lives. Non-disclosure to
children was frequently described, often as a way to protect them from
psychological sequelae. Concealment of widowhood is a coping strategy Nepali
women use to shield themselves against societal stigma and to manage bereavement
in their children. Efforts are needed to support widows in dealing with mental
health issues related to disclosure and the psychosocial impact on their
children.
PMID- 25132372
TI - Exposure to rufinamide and risks of CNS adverse events in drug-resistant
epilepsy: a meta-analysis of randomized, placebo-controlled trials.
AB - AIM: Epilepsy is a complex disease necessitating continuous development of new
therapeutic strategies to encounter drug-resistant cases. Among new adjuvant
antiepileptic drugs, rufinamide is structurally distinct from other antiepileptic
drugs. It is used to treat partial-onset seizures and seizures associated with
Lennox-Gastaut syndrome (LGS) in adult and children. To date, there has been no
attempt to evaluate systematically the risks of adverse events with rufinamide.
METHODS: We performed a quantitative risk analysis of central nervous system
(CNS) adverse events of rufinamide from all randomized, double-blind, add-on,
placebo-controlled trials. The meta-analysis was undertaken with fixed effects
models. RESULTS: Of the 886 publications reviewed, 99 papers were retrieved and
five articles met the inclusion criteria. One thousand two hundred and fifty-two
patients were included. Our study showed that exposure to rufinamide was
associated with a significant increase in risk of somnolence [relative ratio (RR)
1.87; 95% confidence interval (CI) 1.33, 2.62; P = 0.0003], dizziness (RR 2.66;
95% CI 2.00, 3.55; P = 0.00001), fatigue (RR 2.14; 95% CI 1.57, 2.91; P = 0.01)
and headache (RR 1.28; 95% CI 1.02, 1.59, P = 0.03). In addition, exposure to
rufinamide was associated with higher treatment discontinuation rates as compared
with placebo (RR 2.65; 95% CI 1.74, 4.03; P = 0.00001). CONCLUSIONS: The risk of
CNS adverse events appears to be increased in patients exposed to rufinamide as
well as the treatment discontinuation rates. However, although statistical
associations were significant, additional long term safety studies are required
to confirm the clinical significance of these findings, as most reports described
only mild and moderate adverse events.
PMID- 25132373
TI - Human papillomavirus type-specific prevalence in women referred for colposcopic
examination in Beijing.
AB - Human papillomavirus (HPV) is associated with several disorders of the genital
tract, skin, and oropharynx. This study investigated the prevalence of infection
by 37 HPV genotypes among women of the Beijing area in China. Cervical specimens
from 1,082 patients and 165 healthy controls were tested for HPV genotypes using
a chip hybridization assay. Based on the local pathology, patients were divided
into cervicitis and cervical lesion groups. Overall HPV infection rates were
30.5% for the cervicitis group and 78.4% for the cervical lesion group; whereas
infection rates for high-risk HPV types (i.e., those associated with cervical
cancers) were 24.0% and 73.4%, respectively. The most common HPV genotypes were
HPV 52, 16, 81, 58, and 18 in healthy controls, HPV 52, 61, 55, 16, and 53 in
those with cervicitis, HPV 52, 16, 33, 39, and 58 in cervical intraepithelial
neoplasia grade 1, HPV 16, 58, 31, 52, and 33 in cervical intraepithelial
neoplasia grade 2 or grade 3, and HPV 16, 33, 18, 52, and 58 in cervical cancer.
Established high-risk HPV showed two peaks, in patients aged 30-34 and 55-79
years. In Beijing, HPV 16, 52, 58, and 33 are the most prevalent HPV types in
women with cervical lesions, which should affect development of a cervical cancer
vaccination for local use.
PMID- 25132374
TI - Identification and characterization of microRNAs in oilseed rape (Brassica napus)
responsive to infection with the pathogenic fungus Verticillium longisporum using
Brassica AA (Brassica rapa) and CC (Brassica oleracea) as reference genomes.
AB - Verticillium longisporum, a soil-borne pathogenic fungus, causes vascular disease
in oilseed rape (Brassica napus). We proposed that plant microRNAs (miRNAs) are
involved in the plant-V. longisporum interaction. To identify oilseed rape
miRNAs, we deep-sequenced two small RNA libraries made from V. longisporum
infected/noninfected roots and employed Brassica rapa and Brassica oleracea
genomes as references for miRNA prediction and characterization. We identified
893 B. napus miRNAs representing 360 conserved and 533 novel miRNAs, and mapped
429 and 464 miRNAs to the AA and CC genomes, respectively. Microsynteny analysis
with the conserved miRNAs and their flanking protein coding sequences revealed
137 AA-CC genome syntenic miRNA pairs and 61 AA and 42 CC genome-unique miRNAs.
Sixty-two miRNAs were responsive to the V. longisporum infection. We present data
for specific interactions and simultaneously reciprocal changes in the expression
levels of the miRNAs and their targets in the infected roots. We demonstrate that
miRNAs are involved in the plant-fungus interaction and that miRNA168-Argonaute 1
(AGO1) expression modulation might act as a key regulatory module in a compatible
plant-V. longisporum interaction. Our results suggest that V. longisporum may
have evolved a virulence mechanism by interference with plant miRNAs to reprogram
plant gene expression and achieve infection.
PMID- 25132375
TI - Type V collagen counteracts osteo-differentiation of human mesenchymal stem
cells.
AB - In search of novel gene signatures for osteo-differentiation of mesenchymal stem
cells (MSCs), we submitted cDNA preparations from undifferentiated and
differentiating MSCs to differential display- and semiquantitative-PCR and found
down-regulation of COL5A1 in osteo-induced cultures at days 21 and 28, when the
mineralized matrix accumulates. We also cultured osteo-differentiating MSCs onto
type V collagen substrates and found a decrease in the accumulation of
extracellular calcium compared to those grown in uncoated flasks. To our
knowledge, this is first evidence that type V collagen might represent a stromal
component that impairs osteogenesis.
PMID- 25132376
TI - Percutaneous carbon dioxide treatment using a gas mist generator enhances the
collateral blood flow in the ischemic hindlimb.
AB - AIM: Highly concentrated carbon dioxide (CO2) is thought to be useful for
ischemic diseases. We investigated whether treatment with a few micrometers of
CO2 molecules atomized via two fluidnozzles (CO2 mist) exerts an angiogenic
effect in a mouse ischemic hindlimb model. METHODS: Mice with unilateral hindlimb
ischemia were divided into untreated (UT), 100% CO2 gas alone-treated (CG), mixed
air (O2; 20%, N2; 80%) mist-treated (AM) and 100% CO2 mist-treated (CM) groups.
The lower body of the mice was encased in a polyethylene bag filled with each
gaseous agent using a gas mist generator for 10 minutes daily. RESULTS: According
to a laser Doppler analysis, the ischemic hindlimb blood flow was persistently
higher after the seventh day of induction of ischemia in the CM group than in the
UT group. The capillary density was also greater in the CM group on day 28
compared with that observed in the UT group. In addition, the parameters in the
AM and CG groups were similar to those obtained in the UT group. The observed
effects were abolished by the administration of an inhibitor of nitric oxide
synthase (NOS). The vascular endothelial growth factor mRNA expression and
protein levels and the phosphorylated endothelial NOS level were increased in the
CM group compared with that observed in the UT group. A proteomic analysis using
liquid chromatography-tandem mass spectrometry identified novel protein
candidates regulated by CO2 mist. CONCLUSION: Percutaneous CO2 mist therapy may
be useful for treating ischemia-induced angiogenesis.
PMID- 25132377
TI - The expression of groups IIE and V phospholipase A2 is associated with an
increased expression of osteogenic molecules in human calcified aortic valves.
AB - AIM: Eicosanoids play various pathogenic roles in aortic valve calcification.
Eicosanoids are derived from the arachidonic acid generated by phospholipase A2
(PLA2). We therefore sought to determine whether PLA2s are expressed in human
aortic valves and, if so, whether the expression of PLA2s is related to the
expression of osteogenic molecules in these tissues. METHODS: Histological and
gene expression analyses of 38 non-rheumatic aortic valves obtained at the time
of cardiac valve replacement surgery were conducted. Moreover, gene expression
analyses were performed using valve interstitial cells (VICs) obtained from human
aortic valves. RESULTS: Among the PLA2s examined, the degree of immunoreactivity
for PLA2s-IIE and -V was found to significantly correlate with the grade of
calcification in the aortic valves. The degree of immunoreactivity and gene
expression levels of PLA2s-IIE and -V significantly correlated with those of bone
morphogenetic protein (BMP)-2, osteopontin and alkaline phosphatase (ALP). In
addition, immunoreactivity for cyclooxygenase (COX)-1, COX-2 and 5-lipoxygenase,
downstream enzymes of PLA2 in the arachidonic acid cascade, was co-localized with
that for PLA2s-IIE and -V in cells expressing alpha-smooth muscle actin and
macrophages expressing CD68. Furthermore, in the in vitro experiments using
cultured VICs, the mRNA expression levels of BMP-2, osteopontin and ALP were
suppressed by the inhibition of the expression of PLA2s-IIE or -V with specific
siRNAs. CONCLUSIONS: The expression of PLA2s-IIE and -V correlates with the
development of calcification as well as the expression of pro-osteogenic
molecules in human aortic valves, and inhibiting the expression of PLA2s-IIE and
V suppresses the induction of osteogenic molecules in cultured cells. Therefore,
PLA2s-IIE and -V may play a role in the pathogenesis of valve calcification.
PMID- 25132378
TI - Antioxidant effects of statins in the management of cardiometabolic disorders.
AB - Redox systems are key players in vascular health. A shift in redox homeostasis
that results in an imbalance between reactive oxygen species (ROS) generation and
endogenous antioxidant defenses has the potential to create a state of oxidative
stress that subsequently plays a role in the pathogenesis of a number of
diseases, including those of the cardiovascular and metabolic system. Statins,
which are primarily used to reduce the concentration of low-density lipoprotein
cholesterol, have also been shown to reduce oxidative stress by modulating redox
systems. Studies conducted both in vitro and in vivo support the role of
oxidative stress in the development of atherosclerosis and cardiovascular
diseases. Oxidative stress may also be responsible for various diabetic
complications and the development of fatty liver. Statins reduce oxidative stress
by blocking the generation of ROS and reducing the NAD+/NADH ratio. These drugs
also have effects on nitric oxide synthase, lipid peroxidation and the
adiponectin levels. It is possible that the antioxidant properties of statins
contribute to their protective cardiovascular effects, independent of the lipid
lowering actions of these agents. However, possible adverse effects of statins on
glucose homeostasis may be related to the redox system. Therefore, studies
investigating the modulation of redox signaling by statins are warranted.
PMID- 25132380
TI - Closed suction drainage for treatment of septic peritonitis of confirmed
gastrointestinal origin in 20 dogs.
AB - OBJECTIVE: To determine survival rate in dogs with septic peritonitis of
confirmed gastrointestinal origin treated with closed suction drainage. STUDY
DESIGN: Retrospective case series. ANIMALS: Dogs (n = 20) with septic
peritonitis. METHODS: Medical records (2007-2010) of dogs with septic peritonitis
of confirmed gastrointestinal origin treated by closed suction drainage were
reviewed. Information on signalment, clinicopathologic abnormalities, underlying
cause, surgical procedure performed, postoperative management, complications, and
outcome was obtained. RESULTS: Dehiscence of a previous anastomosis was the most
common source of contamination (80%). Drains remained in place, collecting fluid
produced within the abdomen, for a median of 6 days (range, 2-11 days). Eighteen
dogs received nutritional support, and 14 received plasma transfusions. Seventeen
dogs (85%) survived to discharge. CONCLUSIONS: Closed suction drainage together
with resolution of the underlying cause of peritonitis and appropriate
postoperative management is an effective technique for treatment of septic
peritonitis of confirmed gastrointestinal origin in dogs.
PMID- 25132379
TI - Impact of eicosapentaenoic acid treatment on the fibrous cap thickness in
patients with coronary atherosclerotic plaque: an optical coherence tomography
study.
AB - AIM: Previous clinical trials have demonstrated the effectiveness of
eicosapentaenoic acid (EPA) in preventing cardiovascular events. The aim of the
present study was to investigate the effects of EPA treatment on the accumulation
of coronary atherosclerotic plaque using optical coherence tomography (OCT).
METHODS: A total of 46 acute coronary syndrome (ACS) patients without
dyslipidemia were divided into two groups: those who received 1,800 mg/day of EPA
(n = 15) or the control group (n = 31). Serial OCT examinations were performed at
baseline and after eight months of follow-up. The target for the OCT analysis was
non-culprit plaque with a percent diameter of stenosis of 30% to 70% in non
culprit vessels of ACS. RESULTS: Between the baseline and follow-up visits, the
serum EPA levels increased (50 +/- 26 mg/dL to 200 +/- 41 mg/dL, p < 0.001) in
the EPA group, although they did not change in the control group. According to
the OCT analysis, the lipid arc did not change in the EPA group (131 +/- 52
degrees to 126 +/- 54 degrees, p = 0.106) or the control group (137 +/- 50
degrees to 138 +/- 50 degrees, p=0.603). In contrast, the fibrous cap thickness
significantly increased in both the EPA group (169 +/- 70 MUm to 201 +/- 49 MUm,
p < 0.001) and the control group (164 +/- 63 MUm to 174 +/- 72 MUm, p=0.018);
however, the relative change in the fibrous cap thickness was significantly
greater in the EPA group than in the control group (131 +/- 35% vs. 106 +/- 15%,
p = 0.001). CONCLUSIONS: In the present study, the administration of EPA for
eight months significantly increased the fibrous cap thickness in patients with
coronary atherosclerotic plaque.
PMID- 25132381
TI - Photoluminescent nematic liquid crystalline elastomer with a thermomechanical
emission variation function.
AB - Nematic liquid crystalline elastomer (LCE) microactuators are developed, showing
simultaneous thermomechanical deformation and photoluminescence (PL) emission
variation functions. The microactuators are prepared by a method combining soft
lithography and photo-polymerization/crosslinking. 1,4-Bis(alpha-cyano-4
methoxystyryl)benzene as the PL dye is synthesized, characterized, and introduced
into LCEs as a dopant in the preparation process. During the heating process, PL
emission of the LCE micropillars under blue light excitation becomes
significantly weak when the micropillars contract. When cooling down, the
emission completely recovers as the micropillars stretches back to their original
shape. The PL intensity variation at the transition is proved to be related to
the thermomechanical deformation.
PMID- 25132383
TI - How hard is hard enough? An investigation of the force associated with lateral
blunt force trauma to the porcine cranium.
AB - Blunt force trauma forms a substantial portion of deaths worldwide. However, few
studies have attempted to determine the force involved with blunt force trauma to
the lateral part of the head. Nor have many studies been conducted at velocities
exceeding 10 m/s. The acquisition of human tissue for experimental studies is
becoming increasingly difficult. As such, the current study investigates the
trauma and the force involved with cranial blunt force trauma in a porcine model.
Thirty whole porcine heads were subjected to single impact tests on the fronto
parietal region at velocities ranging from 10 m/s to 25 m/s. Half the specimens
were subjected to impact by a short projectile resembling a hammer head and the
other half were subjected to impact with a Hopkinson pressure bar (HPB). Both
implements had the same impact diameter and were machined from the same material.
The HPB is an apparatus commonly used in material testing. Its use to determine
fracture force in whole cranial specimens is novel. Fractures appeared similar in
both the hammer tests and HPB tests. Lacerations and fractures resembled the
shape of the striker surface with the most common fracture observed being a semi
circular depressed fracture. The mean peak fracture force was 7760 N (+/- 4150
N), with a mean displacement of 3.1mm (+/- 1.1mm). Peak fracture forces concur
well with previous studies although no clear trend appears to exist between level
of trauma and peak impact force.
PMID- 25132382
TI - Neutralizing antibodies inhibit HIV-1 infection of plasmacytoid dendritic cells
by an FcgammaRIIa independent mechanism and do not diminish cytokines production.
AB - Plasmacytoid dendritic cells (pDC) expressing FcgammaRIIa are antigen-presenting
cells able to link innate and adaptive immunity and producing various cytokines
and chemokines. Although highly restricted, they are able to replicate HIV-1. We
determined the activity of anti-HIV-1 neutralizing antibodies (NAb) and non
neutralizing inhibitory antibodies (NNIAb) on the infection of primary pDC by HIV
1 primary isolates and analyzed cytokines and chemokines production.
Neutralization assay was performed with primary pDC in the presence of serial
antibodies (Ab) concentrations. In parallel, we measured the release of cytokines
and chemokines by ELISA and CBA Flex assay. We found that NAb, but not NNIAb,
inhibit HIV-1 replication in pDC. This inhibitory activity was lower than that
detected for myeloid dendritic cells (mDC) infection and independent of
FcgammaRIIa expressed on pDC. Despite the complete protection, IFN-alpha
production was detected in the supernatant of pDC treated with NAb VRC01, 4E10,
PGT121, 10-1074, 10E8, or polyclonal IgG44 but not with NAb b12. Production of
MIP-1alpha, MIP-1beta, IL-6, and TNF-alpha by pDC was also maintained in the
presence of 4E10, b12 and VRC01. These findings suggest that pDC can be protected
from HIV-1 infection by both NAb and IFN-alpha release triggered by the innate
immune response during infection.
PMID- 25132384
TI - A self-organizing miR-132/Ctbp2 circuit regulates bimodal notch signals and glial
progenitor fate choice during spinal cord maturation.
AB - Radial glial progenitors play pivotal roles in the development and patterning of
the spinal cord, and their fate is controlled by Notch signaling. How Notch is
shaped to regulate their crucial transition from expansion toward differentiation
remains, however, unknown. miR-132 in the developing zebrafish dampens Notch
signaling via a cascade involving the transcriptional corepressor Ctbp2 and the
Notch suppressor Sirt1. At early embryonic stages, high Ctbp2 levels sustain
Notch signaling and radial glial expansion and concomitantly induce miR-132
expression via a double-negative feedback loop involving Rest inhibition. The
changing balance in miR-132 and Ctbp2 interaction gradually drives the switch in
Notch output and radial glial progenitor fate as part of the larger developmental
program involved in the transition from embryonic to larval spinal cord.
PMID- 25132385
TI - A MYB-domain protein EFM mediates flowering responses to environmental cues in
Arabidopsis.
AB - Plants adjust the timing of the transition to flowering to ensure their
reproductive success in changing environments. Temperature and light are major
environmental signals that affect flowering time through converging on the
transcriptional regulation of FLOWERING LOCUS T (FT) encoding the florigen in
Arabidopsis. Here, we show that a MYB transcription factor EARLY FLOWERING MYB
PROTEIN (EFM) plays an important role in directly repressing FT expression in the
leaf vasculature. EFM mediates the effect of ambient temperature on flowering and
is directly promoted by another major FT repressor, SHORT VEGETATIVE PHASE. EFM
interacts with an H3K36me2 demethylase JMJ30, which forms a negative feedback
regulatory loop with the light-responsive circadian clock, to specifically
demethylate an active mark H3K36me2 at FT. Our results suggest that EFM is an
important convergence point that mediates plant responses to temperature and
light to determine the timing of reproduction.
PMID- 25132386
TI - Genomic instability, driver genes and cell selection: Projections from cancer to
stem cells.
AB - Cancer cells and stem cells share many traits, including a tendency towards
genomic instability. Human cancers exhibit tumor-specific genomic aberrations,
which often affect their malignancy and drug response. During their culture
propagation, human pluripotent stem cells (hPSCs) also acquire characteristic
genomic aberrations, which may have significant impact on their molecular and
cellular phenotypes. These aberrations vary in size from single nucleotide
alterations to copy number alterations to whole chromosome gains. A prominent
challenge in both cancer and stem cell research is to identify "driver
aberrations" that confer a selection advantage, and "driver genes" that underlie
the recurrence of these aberrations. Following principles that are already well
established in cancer research, candidate driver genes have also been suggested
in hPSCs. Experimental validation of the functional role of such candidates can
uncover whether these are bona fide driver genes. The identification of driver
genes may bring us closer to a mechanistic understanding of the genomic
instability of stem cells. Guided by terminologies and methodologies commonly
applied in cancer research, such understanding may have important ramifications
for both stem cell and cancer biology. This article is part of a Special Issue
entitled: Stress as a fundamental theme in cell plasticity.
PMID- 25132387
TI - Interobserver variability of cervical cytology in HIV-infected women.
AB - OBJECTIVES: Our objectives were to determine the reproducibility of cytological
specimen interpretation between two pathologists in human immunodeficiency virus
(HIV)-infected women (from the VIHGY, ANRS CO17 study of human papillomavirus
genital pathology among HIV-positive women) and to analyse the improvement, if
any, between conventional and liquid-based cytology (LBC) interpretations.
MATERIALS AND METHODS: A sample of all abnormal and 40% of randomly selected
normal Papanicolaou (Pap) tests was randomly ordered and read blindly by a second
pathologist using the revised Bethesda terminology 2001. For both conventional
and liquid-based preparations, unweighted and Cicchetti-Allison-weighted kappa
and their 95% confidence intervals (CIs) were calculated. Kappa values were then
compared using the Altman rule to classify the reproducibility of cytological
specimen interpretation. RESULTS: Two hundred and seventy-seven conventional Pap
tests were reviewed, including 79 abnormal and 10 unsatisfactory results. Overall
agreement between the two observers was 78%, with an estimated Cicchetti-Allison
weighted kappa of 0.69 (95%CI, 0.61-0.77). The corresponding values for the 268
LBCs, including 123 abnormal and two unsatisfactory results, were 84% and 0.82
(95%CI, 0.76-0.87), respectively. The reproducibility of LBC interpretations was
significantly higher than that of conventional preparations (P = 0.009) and, for
both laboratories, the percentages of unsatisfactory results were significantly
lower for LBC. CONCLUSION: In HIV-infected women in the combination
antiretroviral therapy era, the strength of agreement was better for LBCs than
for conventional preparations, with a lower percentage of unsatisfactory results.
When available, LBC should be preferred because of its higher reproducibility.
PMID- 25132388
TI - Chronicling changes to the chronic disease prevention landscape in Canada's
public health system 2004-2010.
AB - The collective impact of major shifts in public health infrastructure and
numerous new chronic disease prevention (CDP) capacity-building initiatives that
have taken place in Canada over the last decade is unknown. The objective of this
study was to determine if CDP capacity (i.e., skills and resources) and
involvement in CDP programming improved in public health organizations in Canada
from 2004 to 2010. Data for this repeated cross-sectional study were drawn from
two waves of a national census of organizations mandated to carry out primary
prevention of chronic disease and/or promotion of healthy eating, physical
activity and tobacco control. Medians for continuous variables and frequencies
for categorical variables were compared across time. Neither resources nor level
of priority for CDP increased over time. There was little difference in the
proportion of organizations with high levels of skills and involvement in core
CDP practices (i.e., needs assessment, identification of relevant practices,
planning, evaluation). Skills and involvement in CDP risk factor programming
showed some gains, some steady states and some losses. Specifically, skill and
involvement in tobacco control programming declined markedly while the proportion
of organizations involved in healthy eating and physical activity programming
increased. Skills to address and involvement in programming related to social
determinants of health remained low over time as did involvement in programming
addressing multiple risk factors concurrently. The lack of marked improvement in
CDP capacity between 2004 and 2010 against a backdrop of initiatives favourable
to strengthening the preventive health system in Canada suggests that efforts may
have fallen short.
PMID- 25132389
TI - Science and society: vaccines and public health.
AB - Most public health research is devoted to the measurement of disease burdens and
of the costs and effectiveness of control measures. The history of immunization
provides many colourful examples of various ways in which such measurements are
made, of how they have influenced policies, and of the importance of public
perception of the magnitudes of the various burdens, benefits and risks.
Improving the public's ability to evaluate evidence is itself an important aspect
of public health.
PMID- 25132391
TI - Social capital and immunization against the 2009 A(H1N1) pandemic in the American
States.
AB - The objective of this paper was to investigate the association between contextual
social capital and immunization coverage rates. A cross-sectional, ecologic study
design was used. Three different estimations of contextual social capital in
American states have been used. Data on immunization coverage rates at state
level comes from Centers for Disease Control and Prevention. Correlation
coefficients were calculated to investigate the bivariate association between the
independent variable social capital and the dependent variable 2009 A(H1N1)
immunization coverage rates. A multivariate OLS regression model was used to
investigate the association between contextual social capital and immunization,
under control for state-level health care spending per capita, state population,
population per square mile, and median age in the American States. Results show
that Social capital was strongly correlated with 2009 A(H1N1) immunization
acceptance among American States. In a multivariate regression analysis, the
association remains strong and significant also when controlling state-level
confounders. In conclusion, social capital, at least in a U.S. context, is shown
to be associated with the state-level uptake of vaccination against the 2009
A(H1N1) pandemic.
PMID- 25132390
TI - Measuring the burden of disease due to climate change and developing a forecast
model in South Korea.
AB - OBJECTIVES: Climate change influences human health in various ways, and
quantitative assessments of the effect of climate change on health at national
level are becoming essential for environmental health management. STUDY DESIGN:
This study quantified the burden of disease attributable to climate change in
Korea using disability-adjusted life years (DALY), and projected how this would
change over time. METHODS: Diseases related to climate change in Korea were
selected, and meteorological data for each risk factor of climate change were
collected. Mortality was calculated, and a database of incidence and prevalence
was established. After measuring the burden of each disease, the total burden of
disease related to climate change was assessed by multiplying population
attributable fractions. Finally, an estimation model for the burden of disease
was built based on Korean climate data. RESULTS: The total burden of disease
related to climate change in Korea was 6.85 DALY/1000 population in 2008.
Cerebrovascular diseases induced by heat waves accounted for 72.1% of the total
burden of disease (hypertensive disease 1.82 DALY/1000 population, ischaemic
heart disease 1.56 DALY/1000 population, cerebrovascular disease 1.56 DALY/1000
population). According to the estimation model, the total burden of disease will
be 11.48 DALY/1000 population in 2100, which is twice the total burden of disease
in 2008. CONCLUSIONS: This study quantified the burden of disease caused by
climate change in Korea, and provides valuable information for determining the
priorities of environmental health policy in East Asian countries with similar
climates.
PMID- 25132392
TI - The effects of depression and chronic diseases on the work outcomes of employees:
a prospective study in Northwest China.
AB - A prospective cohort study was conducted to examine the impact of physical and
mental health status on the job loss and job turnover rates in Northwestern
China. There were 1778 employees included in the baseline survey at April 2006
and were followed-up in October 2006. They were classified into four groups:
those with chronic diseases (n = 205), depression (n = 273), both chronic
diseases and depression (n = 96), and a control group (n = 1204). Logistic
regression was used to examine the impact of depression and chronic diseases on
employment between the baseline and the 6-month follow-up interviews. The results
of the analyses showed that participants suffering from depression were more
likely to be unemployed (OR, 1.44; P < 0.05), recently changed jobs (OR, 3.28, P
< 0.001) and earning a lower salary (B = -135.28RMB, P < 0.001). Depression
accompanying chronic diseases had an increased risk of unemployment (OR, 2.05; P
< 0.01). The participants with chronic diseases were more likely to change their
jobs (OR, 2.53; P < 0.05), but this had no significant impact on unemployment and
monthly salary. Overall, the findings suggest that people with depression were at
a higher risk of unemployment and job turnover than people with chronic disease.
PMID- 25132393
TI - Antibacterial usage in English NHS hospitals as part of a national Antimicrobial
Stewardship Programme.
AB - Antimicrobial resistance (AMR) has become a global problem for health care
services, with fewer antimicrobials entering the market and some pathogenic
organisms becoming resistant to commonly used antimicrobials. Antimicrobial
stewardship (AS), including evidence-based standard setting, education and
communication, and audits of practice, has become a key method of preventing the
rise in the rise in AMR. Data on antibiotic consumption are often obtained
through prospective and retrospective point prevalence audits of antibiotic
usage, but such studies are very resource intensive and only provide a snapshot
of consumption. The objective of the study reported here was to examine
longitudinal total antibacterial usage at a national level and cross-sectional
usage at an individual hospital trust level using a commercial database that
captures antimicrobial prescribing from at least 99% of English hospital Trusts.
PMID- 25132394
TI - Radiological predictors of cytoreductive outcomes in patients with advanced
ovarian cancer.
AB - OBJECTIVE: To assess site of disease on preoperative computed tomography (CT) to
predict surgical debulking in patients with ovarian cancer. DESIGN: Two-phase
retrospective cohort study. SETTING: West London Gynaecological Cancer Centre,
UK. POPULATION: Women with stage 3 or 4, ovarian, fallopian or primary peritoneal
cancer undergoing cytoreductive surgery. METHODS: Preoperative CT images were
reviewed by experienced radiologists to assess the presence or absence of disease
at predetermined sites. Multivariable stepwise logistic regression models
determined sites of disease which were significantly associated with surgical
outcomes in the test (n = 111) and validation (n = 70) sets. MAIN OUTCOME
MEASURES: Sensitivity and specificity of CT in predicting surgical outcome.
RESULTS: Stepwise logistic regression identified that the presence of lung
metastasis, pleural effusion, deposits on the large-bowel mesentery and small
bowel mesentery, and infrarenal para-aortic nodes were associated with debulking
status. Logistic regression determined a surgical predictive score which was able
to significantly predict suboptimal debulking (n = 94, P = 0.0001) with an area
under the curve (AUC) of 0.749 (95% confidence interval [95% CI]: 0.652, 0.846)
and a sensitivity of 69.2%, specificity of 71.4%, positive predictive value of
75.0% and negative predictive value of 65.2%. These results remained significant
in a recent validation set. There was a significant difference in residual
disease volume in the test and validation sets (P < 0.001) in keeping with
improved optimal debulking rates. CONCLUSIONS: The presence of disease at some
sites on preoperative CT scan is significantly associated with suboptimal
debulking and may be an indication for a change in surgical planning.
PMID- 25132395
TI - Osteoid osteoma of the phalanx and metacarpal bone: report of 17 cases.
AB - BACKGROUND: Osteoid osteoma (OO) is a slowly progressing benign osteoblastic
tumour. In the hand, this tumour is rare. We propose a review of seventeen cases
of OO of the phalanx and metacarpal bone. PATIENTS AND METHODS: During the
period, between 1998 and 2011, a total of seventeen OO in the hand were confirmed
by the pathological examination. They were 10 women and 7 men with an average age
of 29 years (age range 17-76). The most common site of the tumour was the
proximal phalanx in ten cases, followed by middle phalanx in four cases and
metacarpal bone in three cases. The diagnosis of OO was highly required by
clinical history. Standard radiographs showed variable images, but computed
tomography, and it was useful to facilitate diagnosis and pre-operative planning.
All patients underwent surgery (the tumour resection and autogenous bone
grafting). In post-operative, there was an immediate pain relief with complete
resolution of all symptoms. No recurrence was observed during the last follow-up
period of 4 years and 2 months. CONCLUSION: The diagnosis of OO of the hand can
be difficult, and it should be considered with bony pain or bony swelling,
especially when the history is a chronic one. The CT scan allows visualisation
and precise localisation of such benign tumour of the hand. The care should be
taken to make the excision complete in order to avoid recurrence.
PMID- 25132396
TI - Use of structured expert judgment to forecast invasions by bighead and silver
carp in Lake Erie.
AB - Identifying which nonindigenous species will become invasive and forecasting the
damage they will cause is difficult and presents a significant problem for
natural resource management. Often, the data or resources necessary for
ecological risk assessment are incomplete or absent, leaving environmental
decision makers ill equipped to effectively manage valuable natural resources.
Structured expert judgment (SEJ) is a mathematical and performance-based method
of eliciting, weighting, and aggregating expert judgments. In contrast to other
methods of eliciting and aggregating expert judgments (where, for example, equal
weights may be assigned to experts), SEJ weights each expert on the basis of his
or her statistical accuracy and informativeness through performance measurement
on a set of calibration variables. We used SEJ to forecast impacts of
nonindigenous Asian carp (Hypophthalmichthys spp.) in Lake Erie, where it is
believed not to be established. Experts quantified Asian carp biomass,
production, and consumption and their impact on 4 fish species if Asian carp were
to become established. According to experts, in Lake Erie Asian carp have the
potential to achieve biomass levels that are similar to the sum of biomasses for
several fishes that are harvested commercially or recreationally. However, the
impact of Asian carp on the biomass of these fishes was estimated by experts to
be small, relative to long term average biomasses, with little uncertainty.
Impacts of Asian carp in tributaries and on recreational activities, water
quality, or other species were not addressed. SEJ can be used to quantify key
uncertainties of invasion biology and also provide a decision-support tool when
the necessary information for natural resource management and policy is not
available.
PMID- 25132397
TI - Interleukin-4 and granulocyte-macrophage colony-stimulating factor mediates the
upregulation of soluble vascular endothelial growth factor receptor-1 in RAW264.7
cells-a process in which p38 mitogen-activated protein kinase signaling has an
important role.
AB - BACKGROUND/PURPOSE: Soluble vascular endothelial growth factor receptor-1
(sVEGFR1) antagonizes angiogenesis by inhibiting the biological function of
vascular endothelial growth factor (VEGF). Immature dendritic cells (imDCs)
express high levels of sVEGFR1 during development and are antiangiogenic. This
study aimed to investigate the changes in VEGFR1, sVEGFR1, and VEGF levels during
the development of imDCs and explore the underlying signaling mechanisms.
METHODS: To model the differentiation of imDCs from monocytes, RAW264.7 cells, a
murine monocyte/macrophage cell line, were stimulated by interleukin-4 (IL-4; 10
ng/mL, 20 ng/mL, and 40 ng/mL) and/or by granulocyte-macrophage colony
stimulating factor (GM-CSF; 10 ng/mL, 20 ng/mL, and 50 ng/mL) and/or pretreated
by the p38 inhibitor SB203580. The levels of VEGFR1, sVEGFR1, and VEGF were
detected by reverse transcription polymerase chain reaction (RT-PCR), Western
blot, and enzyme-linked immunosorbent assay (ELISA). RESULTS: IL-4 increased the
VEGFR1 mRNA and sVEGFR1 levels in RAW264.7 (p < 0.05). This increase was
inhibited by SB203580. Granulocyte-macrophage colony-stimulating factor increased
the sVEGFR1 levels, but it had no significant effect on VEGFR1 mRNA levels.
SB203580 decreased the expression of VEGFR1 mRNA induced by GM-CSF, whereas
sVEGFR1 was unaffected. IL-4 had a greater effect on sVEGFR1 levels, compared to
GM-CSF. CONCLUSION: IL-4 and GM-CSF increased sVEGFR1 levels, but did not
significantly effect VEGF expression, and led to the antiangiogenesis properties
of monocytes. p38 Mitogen-activated protein kinase signaling has an important
role in the process.
PMID- 25132398
TI - Comparison of three different techniques for the isolation of viral RNA in
sputum.
AB - BACKGROUND: Respiratory infections are a major cause of morbidity and mortality
worldwide. A high percentage of all respiratory tract infections are caused by
RNA viruses. Real-time PCR is a highly sensitive method for the detection of
respiratory viruses in clinical samples. A good RNA isolation protocol is of high
importance, since RNA is more unstable than DNA and many clinical samples contain
RNAses. OBJECTIVES: To evaluate the performance of three different RNA extraction
protocols for the extraction of respiratory viral RNA from sputum samples
obtained from patients with the suspicion of a viral respiratory tract infection.
STUDY DESIGN: A total of 50 sputum samples, PCR positive for a respiratory RNA
virus, were used for viral RNA isolation with the phenol/chloroform method,
RTP((r)) DNA/RNA virus mini kit and the automated MagNa Pure LC (MPLC) extraction
system. After isolation, real-time PCR was performed for the detection of viral
RNA in the sputum samples. RESULTS: The MPLC extraction increased the detection
probability from 82% (phenol/chloroform) and 86% (RTP((r)) DNA/RNA virus mini
kit) to 94%. In 16% the RTP((r)) DNA/RNA virus mini kit resulted in lower Ct
values compared to the phenol/chloroform method, while in 32% the
phenol/chloroform resulted in lower Ct values. CONCLUSIONS: The extraction of
viral RNA performed with the MPLC extraction method was superior to the
extraction with the RTP((r)) DNA/RNA virus mini kit and to the extraction with
phenol/chloroform. In general, there was no difference in the detection of viral
RNA between the phenol/chloroform extraction method and the RTP((r)) DNA/RNA
virus mini kit.
PMID- 25132400
TI - Family support in the transition to adulthood in Portugal--its effects on
identity capital development, uncertainty management and psychological well
being.
AB - In a familistic southern European society such as the Portuguese, the family has
historically played a prominent role in supporting the negotiation of transition
pathways into adulthood. The present study aimed at capturing (1) the relative
weight of parental financial support and autonomy support in contributing to the
youngsters' psychological well-being (PWB), and (2) the mediating role of
identity capital and uncertainty management in this relationship. A total of 620
participants completed measures of parental support, identity capital,
uncertainty management and PWB. Autonomy support was found to be the strongest
predictor of PWB, both directly and indirectly through its effects on identity
capital and the use of target focused uncertainty management strategies.
Conversely, financial support evidenced only a minor indirect impact through the
mediation of tangible identity capital. Autonomy stimulation may constitute one
of the most developmentally determinant family challenges in assisting the
process of coming of age in Portugal.
PMID- 25132399
TI - Evaluation of RT-PCR and immunohistochemistry as tools for detection of
enterovirus in the human pancreas and islets of Langerhans.
AB - BACKGROUND: Enteroviruses have been implicated in the etiology of type 1
diabetes, supported by immunoreactivity of enteroviral protein in islets, but
presence of enteroviral genome has rarely been reported. Failure to detect
enterovirus with RT-PCR has been attributed to the possible presence of PCR
inhibitors and that only few cells are infected. OBJECTIVES: The aim of this
study was to evaluate strategies for detection of enterovirus in human islets.
STUDY DESIGN: A scenario was modeled with defined infected islets among a large
number of uninfected pancreatic cells and the sensitivity of immunohistochemistry
and PCR for detection of enterovirus was evaluated. RESULTS: Enterovirus was
detected with PCR when only one single human islet, infected in vitro with a low
dose of virus, was mixed with an uninfected pancreatic biopsy. Enterovirus could
not be detected by immunohistochemistry under the same conditions, demonstrating
the superior sensitivity of PCR also in pancreatic tissue with only a small
fraction of infected cells. In addition, we demonstrate that pancreatic cell
culture supernatant does not cause degradation of enterovirus at 37 degrees C,
indicating that under normal culture conditions released virus is readily
detectable. Utilizing PCR, the pancreases of two organ donors that died at onset
of type 1 diabetes were found negative for enterovirus genome despite islet cells
being positive using immunohistochemistry. CONCLUSIONS: These data suggest that
PCR should be the preferred screening method for enterovirus in the pancreas and
suggest cautious interpretation of immunostaining for enterovirus that cannot be
confirmed with PCR.
PMID- 25132401
TI - Serum hsCRP and procalcitonin levels in dyspeptic patients infected with CagA
positive Helicobacter pylori.
PMID- 25132402
TI - The status of 25-hydroxyvitamin D across the spectrum of glucose tolerance among
middle-aged and elderly Chinese individuals.
AB - CONTEXT: Although vitamin D status and its inverse association with diabetes
among White people have been recognized, little research on vitamin D status has
been well conducted in Chinese individuals based on glucose tolerance. OBJECTIVE:
To compare the vitamin D status of Chinese individuals aged 40-75 years based on
the glucose tolerance status. DESIGN AND METHODS: Serum 25OHD was measured in a
cross-sectional sample of 10 038 individuals aged 40-75 years from Lanzhou city,
which is located in western China. RESULTS: People with normal glucose tolerance
(NGT, n = 4744), prediabetes (n = 2808) or diabetes (n = 2486) aged 40-75 years
were included in the study. The difference in 25OHD concentration between people
with NGT and prediabetes was not significant (16.5 vs 16.0 ng/ml, P = 0.773), but
the 25OHD concentration of diabetes was higher than that of subjects with NGT
(16.5 vs 16.5 ng/ml, P = 0.025) and prediabetes (16.5 vs 16.0 ng/ml, P = 0.032)
after adjusting confounders. There was no difference in the prevalence of vitamin
D deficiency between people with NGT and diabetes (74.7% vs 74.0%, P = 0.535),
but the prevalence of vitamin D deficiency of prediabetes was higher than that of
people with NGT (77.0% vs 74.7%, P = 0.024) and diabetes (77.0% vs 74.0%, P =
0.012). CONCLUSIONS: Although vitamin D status was significantly different across
the spectrum of glucose tolerance in middle-aged and elderly Chinese individuals,
the difference was not clinically significant. The results, however, highlight
the very high prevalence of vitamin D deficiency in this population and should
raise the awareness of this important public health issue among health-care
providers.
PMID- 25132403
TI - SIRT1 directly regulates SOX2 to maintain self-renewal and multipotency in bone
marrow-derived mesenchymal stem cells.
AB - SOX2 is crucial for the maintenance of the self-renewal capacity and multipotency
of mesenchymal stem cells (MSCs); however, the mechanism by which SOX2 is
regulated remains unclear. Here, we report that RNA interference of sirtuin 1
(SIRT1) in human bone marrow (BM)-derived MSCs leads to a decrease of SOX2
protein, resulting in the deterioration of the self-renewal and differentiation
capacities of BM-MSCs. Using immunoprecipitation, we demonstrated direct binding
between SIRT1 and SOX2 in HeLa cells overexpressing SOX2. We further discovered
that the RNA interference of SIRT1 induces the acetylation, nuclear export, and
ubiquitination of SOX2, leading to proteasomal degradation in BM-MSCs. SOX2
suppression by trichostatin A (TSA), a known histone deacetylase inhibitor, was
reverted by treatment with resveratrol (0.1 and 1 uM), a known activator of SIRT1
in BM-MSCs. Furthermore, 0.1 and 1 uM resveratrol reduced TSA-mediated
acetylation and ubiquitination of SOX2 in BM-MSCs. SIRT1 activation by
resveratrol enhanced the colony-forming ability and differentiation potential to
osteogenic and adipogenic lineages in a dose-dependent manner. However, the
enhancement of self-renewal and multipotency by resveratrol was significantly
decreased to basal levels by RNA interference of SOX2. These results strongly
suggest that the SIRT1-SOX2 axis plays an important role in maintaining the self
renewal capability and multipotency of BM-MSCs. In conclusion, our findings
provide evidence for positive SOX2 regulation by post-translational modification
in BM-MSCs through the inhibition of nuclear export and subsequent
ubiquitination, and demonstrate that SIRT1-mediated deacetylation contributes to
maintaining SOX2 protein in the nucleus.
PMID- 25132404
TI - Linking oxygen availability with membrane potential maintenance and K+ retention
of barley roots: implications for waterlogging stress tolerance.
AB - Oxygen deprivation is a key determinant of root growth and functioning under
waterlogging. In this work, changes in net K(+) flux and membrane potential (MP)
of root cells were measured from elongation and mature zones of two barley
varieties under hypoxia and anoxia conditions in the medium, and as influenced by
ability to transport O2 from the shoot. We show that O2 deprivation results in an
immediate K(+) loss from roots, in a tissue- and time-specific manner, affecting
root K(+) homeostasis. Both anoxia and hypoxia induced transient membrane
depolarization; the extent of this depolarization varied depending on severity of
O2 stress and was less pronounced in a waterlogging-tolerant variety. Intact
roots of barley were capable of maintaining H(+) -pumping activity under hypoxic
conditions while disrupting O2 transport from shoot to root resulted in more
pronounced membrane depolarization under O2 -limited conditions and in anoxia a
rapid loss of the cell viability. It is concluded that the ability of root cells
to maintain MP and cytosolic K(+) homeostasis is central to plant performance
under waterlogging, and efficient O2 transport from the shoot may enable
operation of the plasma membrane H(+) -ATPase in roots even under conditions of
severe O2 limitation in the soil solution.
PMID- 25132405
TI - Baicalein induces autophagic cell death through AMPK/ULK1 activation and
downregulation of mTORC1 complex components in human cancer cells.
AB - Baicalein, a flavonoid and aglycon hydrolyzed from baicalin, has anticancer
properties in several human carcinomas, but its molecular mechanisms of action
remain unclear. Here, we show that baicalein leads to human cancer cell death by
inducing autophagy rather than apoptosis, because cell death induced by baicalein
was completely reversed by suppressing the expression levels of key molecules in
autophagy such as Beclin 1, vacuolar protein sorting 34 (Vps34), autophagy
related (Atg)5 and Atg7, but not by pan-caspase inhibitor. Our data revealed that
baicalein significantly increased the number of green fluorescence protein
cytosol-associated protein light chain 3 (GFP-LC3)-containing puncta and LC3B-II
expression levels, which were further enhanced by chloroquine treatment.
Furthermore, a luciferase-based reporter assay showed that the ratio of RLuc
LC3wt/RLuc-LC3G120A was greatly reduced. The data suggested that baicalein
induced not only autophagosome formation, but also autophagic flux. Experiments
using short interfering RNAs and pharmacological inhibitors revealed that Beclin
1, Vps34, Atg5, Atg7 and UNC-51 (Caenorhabditis elegans)-like kinase 1 (ULK1)
play pivotal roles in mediating baicalein-induced autophagy. Moreover, baicalein
activated AMP-activated protein kinase (AMPK)alpha, leading to ULK1 activation
through phosphorylation at Ser555, whereas both protein and mRNA levels of
mammalian target of rapamycin (mTOR) and Raptor, upstream inhibitors of ULK1 and
autophagy, were markedly downregulated by baicalein. Our data suggest that the
anticancer effects of baicalein are mainly due to autophagic cell death through
activation of the AMPK/ULK1 pathway and inhibition of mTOR/Raptor complex 1
expression. These results provide new mechanistic insights into the anticancer
functions of autophagy inducers, such as baicalein, which may be used as
potential therapeutics for cancer treatment.
PMID- 25132406
TI - Prevalence of peri-implant inflammatory disease in patients with a history of
periodontal disease who receive supportive periodontal therapy.
AB - OBJECTIVES: To describe the status of implants in periodontally compromised
patients who regularly receive supportive periodontal therapy (SPT) and to
determine the factors associated to peri-implant inflammatory disease in those
patients. MATERIAL AND METHODS: Clinical and radiographic data of implants in
periodontal patients who, after being treated and included in a SPT programme,
wore implant prostheses for at least 6 months were recorded. The implants were
classified according to the criteria of the 6th European Workshop on
Periodontology in health, mucositis and peri-implantitis. Logistic regression
analysis was performed to analyse the individual and adjusted effects of each
study variable on mucositis or peri-implantitis, using SUDAAN to account for
clustering (multiple implants within the patient). RESULTS: A total of 786
implants were placed in 239 patients. At patient level, 60.3%, 24.7% and 15.1%
were classified as healthy, mucositis and peri-implantitis patients,
respectively. At implant level, the respective percentages were 77.4%, 12.8% and
9.8%. For mucositis, at implant level, the adjusted ORs indicate a significant
association with plaque index (P = 0.050), type of periodontitis (P = 0.030) and
location (P = 0.045). For peri-implantitis, the adjusted ORs indicate a
significant association with plaque index (P < 0.001) and location (P = 0.002).
CONCLUSIONS: The prevalence of peri-implant inflammatory disease in periodontal
patients who regularly undergo SPT is clinically significant. The factors
associated with peri-implant inflammatory disease were plaque index and implant
location, and mucositis was also affected by the type of periodontitis the
patient had.
PMID- 25132407
TI - Comprehensive hands-on training for influenza vaccine manufacturing: a WHO-BARDA
BTEC partnership for global workforce development.
AB - The critical need for enhancing influenza pandemic preparedness in many
developing nations has led the World Health Organization (WHO) and the Biomedical
Advanced Research and Development Authority (BARDA), part of the U.S. Department
of Health and Human Services (HHS), to develop an international influenza vaccine
capacity-building program. Among the critical limitations faced by many of these
nations is lack of access to training programs for staff supporting operations
within vaccine production facilities. With support from BARDA, the
Biomanufacturing Training and Education Center (BTEC) at North Carolina State
University has addressed this need for training by developing and delivering a
comprehensive training program, consisting of three courses: Fundamentals of cGMP
Influenza Vaccine Manufacturing, Advanced Upstream Processes for Influenza
Vaccine Manufacturing, and Advanced Downstream Processes for Influenza Vaccine
Manufacturing. The courses cover process design, transfer, and execution at
manufacturing scale, quality systems, and regulations covering both manufacturing
and approval of pandemic vaccines. The Fundamentals course focuses on the
concepts, equipment, applicable regulations, and procedures commonly used to
produce influenza vaccine. The two Advanced courses focus on process design,
scale up, validation, and new technologies likely to improve efficiency of
vaccine production. All three courses rely on a combination of classroom
instruction and hands-on training in BTEC's various laboratories. Each course
stands alone, and participants may take one or more of the three courses. Overall
participant satisfaction with the courses has been high, and follow-up surveys
show that participants actively transferred the knowledge they gained to the
workplace. Future plans call for BTEC to continue offering the three courses and
to create an online version of several modules of the Fundamentals course.
PMID- 25132408
TI - The sensory world of fish and fisheries: impact of human activities--an
international conference to evaluate the effects of environmental changes on the
sensory world of fish/aquatic animals and fisheries.
PMID- 25132409
TI - Looking deeper than (just) below the surface: response.
PMID- 25132410
TI - Research review: Polygenic methods and their application to psychiatric traits.
AB - BACKGROUND: Despite evidence from twin and family studies for an important
contribution of genetic factors to both childhood and adult onset psychiatric
disorders, identifying robustly associated specific DNA variants has proved
challenging. In the pregenomics era the genetic architecture (number, frequency
and effect size of risk variants) of complex genetic disorders was unknown.
Empirical evidence for the genetic architecture of psychiatric disorders is
emerging from the genetic studies of the last 5 years. METHODS AND SCOPE: We
review the methods investigating the polygenic nature of complex disorders. We
provide mini-guides to genomic profile (or polygenic) risk scoring and to
estimation of variance (or heritability) from common SNPs; a glossary of key
terms is also provided. We review results of applications of the methods to
psychiatric disorders and related traits and consider how these methods inform on
missing heritability, hidden heritability and still-missing heritability.
FINDINGS: Genome-wide genotyping and sequencing studies are providing evidence
that psychiatric disorders are truly polygenic, that is they have a genetic
architecture of many genetic variants, including risk variants that are both
common and rare in the population. Sample sizes published to date are mostly
underpowered to detect effect sizes of the magnitude presented by nature, and
these effect sizes may be constrained by the biological validity of the
diagnostic constructs. CONCLUSIONS: Increasing the sample size for genome wide
association studies of psychiatric disorders will lead to the identification of
more associated genetic variants, as already found for schizophrenia. These loci
provide the starting point of functional analyses that might eventually lead to
new prevention and treatment options and to improved biological validity of
diagnostic constructs. Polygenic analyses will contribute further to our
understanding of complex genetic traits as sample sizes increase and as sample
resources become richer in phenotypic descriptors, both in terms of clinical
symptoms and of nongenetic risk factors.
PMID- 25132412
TI - Successful management of chronic postsurgical pain following total knee
replacement.
AB - We report reversal of chronic postsurgical pain (CPSP) along with functional
restoration after total knee replacement (TKR) in two patients, using a
combination therapy that included ultrasonography-guided pulsed radiofrequency
(PRF) of nerves supplying the knee to provide pain relief, along with dry
needling (DN) to relax myofascial triggers/bands that caused painful stiffness
and restricted movement of muscles acting across the knee. Both patients showed
demonstrable pain relief, as evidenced by changes in pain as assessed on the
Numeric Rating Scale (patient 1: 4-9/10 [pre-treatment] to 0-3/10 [6 months post
treatment]; patient 2: 5-9/10 to 0-4/10), Oxford Knee Score (patient 1: 17 to 40;
patient 2: 12 to 39), Self-Administered Leeds Assessment of Neuropathic Symptoms
and Signs score (patient 1: 16 to 0; patient 2: 18 to 0), and Patient Health
Questionnaire-9 score (patient 1: 17 to 2; patient 2: 20 to 2). The selection of
the PRF-and-DN combination for treating post-TKR CPSP was based on a new idea
that CPSP is a neuromyopathic phenomenon involving both sensory and motor
neuropathy. It has evolved from our experience of 8 years. Physiotherapy worked
synergistically with DN, optimizing muscle performance and pain relief.
PMID- 25132411
TI - Secukinumab administration by pre-filled syringe: efficacy, safety and usability
results from a randomized controlled trial in psoriasis (FEATURE).
AB - BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody,
demonstrated efficacy and safety in moderate-to-severe plaque psoriasis when
administered via subcutaneous injection. Self-administration by pre-filled
syringe (PFS) can offer patients clinical benefits of a drug, with increased
convenience. OBJECTIVES: To assess efficacy, safety and usability of secukinumab
administration via PFS in subjects with moderate-to-severe plaque psoriasis.
MATERIALS AND METHODS: Subjects in this phase 3 trial were randomized 1 : 1 : 1
to secukinumab 300 or 150 mg or matching placebo. Results to week 12 are
presented here. Each treatment was delivered using a PFS once weekly to week 4,
and again at week 8. Co-primary endpoints were secukinumab superiority over
placebo for week 12 PASI 75 (>= 75% reduction in Psoriasis Area and Severity
Index) and IGA mod 2011 (2011 modified Investigator's Global Assessment) 0/1
response rates. Secondary endpoints included PFS usability, determined by
observer rating of successful, hazard-free self-injection and subject rating of
acceptability by the Self-Injection Assessment Questionnaire (SIAQ). RESULTS: Co
primary endpoints were met, with demonstration of superiority for each
secukinumab dose vs. placebo at week 12 (PASI 75: 75.9%, 69.5% and 0% for
secukinumab 300 mg, 150 mg and placebo; IGA mod 2011 0/1: 69.0%, 52.5% and 0%,
respectively; P < 0.0001 for all comparisons vs. placebo). PFS usability was
high: 100% of subjects successfully self-administered treatment at week 1, and
subjects reported high SIAQ-assessed acceptability of the PFS throughout the
trial. No new/unexpected safety signals were observed. CONCLUSIONS: Secukinumab
administration by PFS was effective, with an acceptable safety profile and high
usability. The PFS provides a reliable, convenient form of secukinumab
administration in subjects with moderate-to-severe plaque psoriasis.
PMID- 25132413
TI - Microextraction sample preparation techniques in biomedical analysis.
AB - Biologically active compounds are found in biological samples at relatively low
concentration levels. The sample preparation of target compounds from biological,
pharmaceutical, environmental, and food matrices is one of the most time
consuming steps in the analytical procedure. The microextraction techniques are
dominant. Metabolomic studies also require application of proper analytical
technique for the determination of endogenic metabolites present in biological
matrix on trace concentration levels. Due to the reproducibility of data,
precision, relatively low cost of the appropriate analysis, simplicity of the
determination, and the possibility of direct combination of those techniques with
other methods (combination types on-line and off-line), they have become the most
widespread in routine determinations. Additionally, sample pretreatment
procedures have to be more selective, cheap, quick, and environmentally friendly.
This review summarizes the current achievements and applications of
microextraction techniques. The main aim is to deal with the utilization of
different types of sorbents for microextraction and emphasize the use of new
synthesized sorbents as well as to bring together studies concerning the
systematic approach to method development. This review is dedicated to the
description of microextraction techniques and their application in biomedical
analysis.
PMID- 25132414
TI - Beyond the use of modifiers in selective alkyne hydrogenation: silver and gold
nanocatalysts in flow mode for sustainable alkene production.
AB - We report on the excellent stereo and chemoselectivity of nanosized silver and
gold catalysts in the three-phase hydrogenation of acetylenic compounds under
flow chemistry conditions. The materials featuring metal nanoparticles in the
range of 2-21 nm were prepared by spray deposition or incipient wetness
impregnation of silver nitrate and sol immobilisation of gold chloride on
different carriers (Al2O3, SiO2, TiO2, and carbon), followed by activation in
various atmospheres. The samples were characterised by ICP-OES, N2 sorption, XPS,
HAADF-STEM, and HRTEM, and evaluated in a continuous-flow flooded-bed micro
reactor. Both metals display optimal activities for particles below 5 nm,
enabling stable operation at T = 373 K and P = 10 bar. While the performance of
the silver catalysts is less influenced by the support, the gold nanoparticles
exhibit significant activity only when deposited on TiO2, likely due to the
strong metal-support interaction. Hydrogenations of functionalised alkynes reveal
that silver and gold match, and in some cases exceed, the selectivity of
benchmark palladium-based catalysts. Furthermore, in contrast to Pd, the Ag and
Au samples require no modifiers, which brings fundamental and practical
simplifications for their understanding and large scale manufacture. Therefore,
these materials could be advantageously used for the continuous production of
olefinic intermediates in the fine chemical and pharmaceutical industries.
PMID- 25132415
TI - Communicating developmental psychobiology to the masses: why psychobiologists
should contribute to Wikipedia.
PMID- 25132416
TI - Breast vs. the rest: a response to Koczwara and Ward.
PMID- 25132417
TI - Determination of rifampicin in rat plasma by modified large-volume direct
injection RAM-HPLC and its application to a pharmcokinetic study.
AB - A direct large volume injection high-performance liquid chromatography (HPLC)
method with homemade restricted-access media (RAM) pre-column and combined with a
column-switching valve was established and developed for determination rifampicin
(RIP) in rat plasma. The rat plasma samples (100 MUL) were injected directly onto
pre-column, where RIP was retained and pre-concentrated, while proteins were
washed to waste using a methanol-water (5:95) as the mobile phase at a flow rate
of 1 mL/min. Then, by rotation of the switching valve at 5 min, the RIP were
eluted from the pre-column and transferred to an Luna C18 analytical column by
the chromatographic mobile phase consisting of methanol-acetonitrile-10 mm
ammonium format (60:5:35) at a flow rate of 1 mL/min. The total analytical run
time was 15 min with UV detection wavelength at 254 nm. Carbamazepine was used as
the internal standard. Excellent linear correlation (r = 0.9993) was obtained in
the range of 0.25-8 ug/mL for rat plasma. The intra-day and inter-day precisions
of RIP were all <5.0%. The recoveries were in the range of from 99.98-113.66% for
plasma. This on-line RAM-HPLC method was successfully applied to the
pharmacokinetic study of RIP in rat plasma.
PMID- 25132418
TI - Increased proliferation and decreased membrane permeability as defense mechanisms
of Fusobacterium nucleatum against human neutrophilic peptide-1.
AB - Human neutrophilic peptides (HNPs) constitute a class of host defense molecules,
which contribute to the non-oxidative killing of bacteria and other
microorganisms. Since the adaptability is crucial to bacterial survival in
changing environments, it is of interest to know how Fusobacterium nucleatum, the
major bridge organism connecting early and late colonizers in dental biofilms,
defends itself against HNPs. This study aimed to examine the planktonic growth,
membrane permeability, and biofilm formation characteristics as defense
mechanisms of F. nucleatum against HNP-1. In all experiments, the type strain of
F. nucleatum (ssp. nucleatum ATCC 25586) and two clinical strains (ssp. nucleatum
AHN 9508 and ssp. polymorphum AHN 9910) were used. Planktonic growth (measured in
colony forming units), capsular polysaccharide production (visualized by Ziehl
Neelsen stain), membrane permeability (demonstrated as N-phenyl-1-naphthylamine
uptake), biofilm formation, and established biofilm development (measured as
total mass and polysaccharide levels) were analyzed in the presence of 0 MUg/ml
(control), 1 MUg/ml, 5 MUg/ml, and 10 MUg/ml of HNP-1. Planktonic growth of the
strains AHN 9508 and ATCC 25586 were significantly (p<0.05) increased in the
presence of HNP-1, while their membrane permeability decreased (p<0.005) in the
planktonic form. HNP-1 decreased the biofilm formation of the strains ATCC 25586
and AHN 9910, whereas it increased the growth of the strain AHN 9508 in
established biofilms. Capsule formation and polysaccharide production were not
observed in any strain. We conclude that the inhibition of the membrane
permeability and the increase in planktonic and established biofilm growth could
act as bacterial defense mechanisms against neutrophilic defensins. In addition,
this strain-dependent survival ability against HNP-1 may explain the variation in
the virulence of different F. nucleatum strains.
PMID- 25132419
TI - Diagnosis, management and outcome of early anastomotic leakage following
colorectal anastomosis using a compression device: is it different?
AB - AIM: Compression anastomosis has proved to be safe for rectal reconstruction with
leak rates comparable to those observed using circular stapling devices. However,
there are no data on whether the metallic compression ring alters the ease of
diagnosis or the treatment in cases of leakage. In this study, we present our
experience with early leakage following compression anastomosis. METHOD: A
prospective registry was used for data review. Patients with anastomotic leakage
following compression anastomosis between November 2008 and September 2013 were
included. RESULTS: In all, 197 (92 female) patients were operated using a novel
compression device. Early leakage was found in 10 (5.1%) patients after a median
of 5 (3-14) days. The radiologist was able to detect leakage using CT in nine out
of 10 cases unequivocally. Removal of the ring was necessary in eight of the 10
cases, and salvage of the anastomosis was feasible on six occasions. In all
diverted cases with a low anastomosis, a transanal repair of the defect was
feasible in three cases, including a single patient with complete separation of
the anastomosis. CONCLUSION: Artefacts on the CT scan caused by the compression
ring did not hamper the diagnosis of anastomotic leakage. Removal of the ring in
the early postoperative period is not associated with complete separation of the
bowel ends. Salvage of anastomosis is feasible in most cases.
PMID- 25132420
TI - Dye-sensitized solar cell from polyaniline-ZnS nanotubes and its characterization
through impedance spectroscopy.
AB - Polyaniline (PANI)-zinc sulphide (ZnS) nanocomposites (PAZs) are synthesized by
polymerizing aniline in the presence of acetic acid with different concentrations
of ZnS nanoparticles (NPs). FESEM and TEM images indicate the nanotube morphology
of PANI and ZnS NPs remain adhered to the nanotube surface, but at higher ZnS
concentration the nanotube morphology is lost. UV-vis spectra indicate PANI is in
the doped state and the doping increases with an increase in ZnS concentration.
Fluorescence intensity passes through a minimum with ZnS content and the dc
conductivity of the composites gradually increases with an increase in ZnS NP
concentration. The I-V plot of PAZ composites indicates that the photocurrent is
higher than that of the dark current at each voltage, and the device exhibits
reversible turning "on" and "off" by switching the white light illumination "on"
and "off". Dye-sensitized solar cells fabricated with PAZ composites display a
reasonably higher power conversion efficiency (eta = 3.38%) than pure ZnS NPs. An
attempt is made to shed light on the operating mechanism of the DSSC from the
impedance data using a Cole-Cole plot by drawing an equivalent circuit
illustrating the different electronic and ionic transport processes within the
cell.
PMID- 25132421
TI - A metal-free strategy to release chemisorbed H2 from hydrogenated boron nitride
nanotubes.
AB - Chemisorbed hydrogen on boron nitride nanotubes (BNNT) can only be released
thermally at very high temperatures above 350 degrees C. However, no catalyst
has been identified that could liberate H2 from hydrogenated BN nanotubes under
moderate conditions. Using different density functional methods we predict that
the desorption of chemisorbed hydrogen from hydrogenated BN nanotubes can be
facilitated catalytically by triflic acid at low free-energy activation barriers
and appreciable rates under metal free conditions and mildly elevated
temperatures (40-50 degrees C). Our proposed mechanism shows that the acid is
regenerated in the process and can further facilitate similar catalytic release
of H2 , thus suggesting all the chemisorbed hydrogen on the surface of the
hydrogenated nanotube can be released in the form of H2 . These findings
essentially raise hope for the development of a sustainable chemical hydrogen
storage strategy in BN nanomaterials.
PMID- 25132422
TI - An analysis of genetic factors related to risk of inflammatory bowel disease and
colon cancer.
AB - BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) have a higher
risk of developing colorectal cancer than the general population. Genome-wide
association studies have identified and replicated several loci associated with
risk of IBD; however, it is currently unknown whether these loci are also
associated with colon cancer risk. METHODS: We selected 15 validated SNPs
associated with risk of either Crohn's disease, ulcerative colitis, or both in
previous GWAS and tested whether these loci were also associated with colon
cancer risk in a two-stage study design. RESULTS: We found that rs744166 in STAT3
was associated with colon cancer risk in two studies; however, the direction of
the observation was reversed in TP53 mutant tumors possibly due to a
nullification of the effect by mutant p53. The SNP, which lies within intron 1 of
the STAT3 gene, was associated with lower expression of STAT3 mRNA in TP53 wild
type, but not mutant, tumors. CONCLUSIONS: These data suggest that the STAT3
locus is associated with both IBD and cancer. Further understanding the function
of this variant in relation to TP53 could possibly explain the role of this gene
in autoimmunity and cancer. Furthermore, an analysis of this locus, specifically
in a population with IBD, could help to resolve the relationship between this SNP
and cancer.
PMID- 25132424
TI - The growth response of ostrich (Struthio camelus var. domesticus) chicks fed on
diets with three different dietary protein and amino acid concentrations.
AB - 1. Feeding costs are the largest expense in an ostrich production system, and
protein is one of the more expensive components of the diet. This study evaluated
the growth response of ostrich chicks on diets containing different
concentrations of protein (amino acids). The diets were formulated to contain
three concentrations of protein (one diet with 20% less protein than the
conventional concentration, L; one diet with the conventional concentration of
protein, M and one diet with 20% more protein than the conventional
concentration, H) for each of the phase diets. The phase diets were pre-starter,
starter, grower and finisher. 2. This study includes the analysis of ostrich body
weight (BW) by modelling growth with linear polynomial and non-linear functions
for all the data not separated for treatments. In total, 3378 BW recordings of 90
animals were collected weekly from hatch (d 0) to 287 d (41 weeks) of age. 3.
Seven non-linear growth models and three linear polynomial models were fitted to
the data. The growth functions were compared by using Akaike's information
criterion (AIC). For the non-linear models, the Bridges and Janoschek models had
the lowest AIC values for the H treatment, while the Richards curve had the
lowest value for M and the von Bertalanffy for the L treatment. 4. For the linear
polynomial models, the linear polynomial of the third degree had the lowest AIC
values for all three treatments, thus making it the most suitable model for the
data; therefore, the predictions of this model were used to interpret the growth
data. Significant differences were found between treatments for growth data. 5.
The results from this study can aid in describing the growth of ostriches
subjected to optimum feeding conditions. This information can also be used in
research when modelling the nutrient requirements of growing birds.
PMID- 25132423
TI - Completeness and validity in a national clinical thyroid cancer database:
DATHYRCA.
AB - BACKGROUND: Although a prospective national clinical thyroid cancer database
(DATHYRCA) has been active in Denmark since January 1, 1996, no assessment of
data quality has been performed. The purpose of the study was to evaluate
completeness and data validity in the Danish national clinical thyroid cancer
database: DATHYRCA. STUDY DESIGN AND SETTING: National prospective cohort.
Denmark; population 5.5 million. Completeness of case ascertainment was estimated
by the independent case ascertainment method using three governmental registries
as a reference. The reabstracted record method was used to appraise the validity.
For validity assessment 100 cases were randomly selected from the DATHYRCA
database; medical records were used as a reference. RESULT: The database held
1934 cases of thyroid carcinoma and completeness of case ascertainment was
estimated to 90.9%. Completeness of registration was around or above 90% in most
instances. Perfect agreement on the diagnosis of thyroid carcinoma was found,
both inter- and intra-observer, and kappa values of selected variables showed
overall good to excellent agreement. CONCLUSION: In a setup with public health
insurance, personal identity numbers and extended governmental databases, it is
possible to establish national clinical cancer databases with a satisfactory
completeness and validity. The DATHYRCA database is considered reliable in terms
of describing thyroid carcinoma at a national level.
PMID- 25132425
TI - Clinical evaluation of ezetimibe on bile lithogenicity in humans: Use of
transnasal endoscopy for bile sampling.
AB - AIM: Ezetimibe inhibits cholesterol absorption by blocking Niemann-Pick C1-like 1
proteins (NPC1L1) expressed in the small intestine. Because NPC1L1 is also
expressed in human liver, ezetimibe conceivably alters biliary lipid
compositions. Here, we performed a clinical trial investigating the effect of
ezetimibe on biliary lipids using transnasal endoscopy for bile collection.
METHODS: Eight patients with dyslipidemia enrolled in this study completed blood
and bile sampling before and at 3 months after ezetimibe treatment (10 mg/day),
and the samples are analyzed. RESULTS: Endoscopic bile sampling was performed
safely and painlessly. Serum sterol-based biomarkers declared decreased
cholesterol absorption and increased synthesis. On analysis of biliary lipids,
four of the eight patients showed relative decrease of cholesterol and increase
of bile acids with improved lithogenicity while the remainder exhibited the
symmetrical changes. CONCLUSION: Our data suggests that biliary lithogenicity is
not worsened by ezetimibe. The regulation of biliary cholesterol is presumably
multifactorial such as body cholesterol pool size and biliary cholesterol
reabsorption by NPC1L1 in the liver.
PMID- 25132426
TI - Who benefits most from Head Start? Using latent class moderation to examine
differential treatment effects.
AB - Head Start (HS) is the largest federally funded preschool program for
disadvantaged children. Research has shown relatively small impacts on cognitive
and social skills; therefore, some have questioned its effectiveness. Using data
from the Head Start Impact Study (3-year-old cohort; N = 2,449), latent class
analysis was used to (a) identify subgroups of children defined by baseline
characteristics of their home environment and caregiver and (b) test whether the
effects of HS on cognitive, and behavioral and relationship skills over 2 years
differed across subgroups. The results suggest that the effectiveness of HS
varies quite substantially. For some children there appears to be a significant,
and in some cases, long-term, positive impact. For others there is little to no
effect.
PMID- 25132428
TI - Cytogenetic studies and their prognostic contribution in 565 Chinese patients
with primary myelofibrosis.
AB - To study the feature and prognostic contribution of cytogenetic information in
Chinese patients with primary myelofibrosis (PMF), we analyzed cytogenetic data
from 565 patients with PMF. One hundred and sixty-two subjects (29%) had abnormal
karyotypes, including trisomy 8 (45; 28%), deletion of 20q (25; 15%), deletion of
13q (13; 8%), deletion of 11q (12; 7%), and abnormal chromosome 1 (21; 13%);
balanced translocations (14; 9%); a complex karyotype (CK; 30; 19%), and a
monosomal karyotype (MK; 19; 12%). Using these data, we showed that the Dynamic
International Prognostic Scoring System (DIPSS)-plus, which includes cytogenetic
information, is a better survival predictor than the DIPSS. We next used our data
to construct the following two cytogenetic-based cohorts: (1) favorable karyotype
subjects with a normal karyotype, a CK that is not a MK, +8 only or a balanced
translocation only and (2) unfavorable karyotype-all others. The median survival
times were not reached and were 52 month (95% CI, 32-72 months; P = 0.01) in
patients with favorable and unfavorable karyotypes, respectively. These data
provided the detailed cytogenetic information in Chinese patients with PMF and
confirmed the impact of cytogenetic abnormalities on survival in Chinese
patients.
PMID- 25132427
TI - Controlled-rate freezing to regulate the structure of collagen-glycosaminoglycan
scaffolds in engineered skin substitutes.
AB - Controlled-rate freezing (CRF) of biopolymer scaffolds may increase
reproducibility of microstructure compared with analog processes. Freezing of
collagen-glycosaminoglycan (CG) scaffolds by CRF with liquid nitrogen at chamber
cooling rates of -80, -40, -20, or -10 degrees C/min, was compared with
submersion in 95% ethanol at -55 degrees C. Cooling rates of -80 or -40 degrees
C/min generated scaffolds with pore areas and pore fractions that were comparable
to scaffolds frozen in ethanol. Test and control scaffolds were populated with
human dermal fibroblasts and epidermal keratinocytes to generate engineered skin
substitutes (ESS) and evaluated for surface hydration and mitochondrial
metabolism. ESS with scaffolds frozen by CRF at -80 or -40 degrees C/min were
comparable with, or better than, ESS with control scaffolds (p < 0.05). These
results demonstrate that fabrication of CG scaffolds by CRF offers advantages of
digital programming, as well as greater reproducibility, safety, and simplicity
than submersion in chilled ethanol without compromise of biological properties
required for biomedical applications.
PMID- 25132430
TI - Fever, diarrhoea and buttock pain in a 15-year-old female traveller (case
presentation).
PMID- 25132431
TI - Editor's comments.
PMID- 25132432
TI - Fever, diarrhoea and buttock pain in a 15-year-old female traveller (discussion
and diagnosis).
PMID- 25132433
TI - [Cancer Plan 3 and molecular pathology: serendipity in pathology?].
PMID- 25132434
TI - [The Canadian Association of Pathology guidelines for establishing a diagnostic
telepathology service using whole-slide imaging].
PMID- 25132435
TI - [Pathology of gallbladder and extrahepatic bile ducts. Introduction].
PMID- 25132438
TI - [Pathology of gallbladder and extrahepatic bile ducts. Case 1. Alcalculous
gangrenous cholecystitis].
PMID- 25132439
TI - [Pathology of the gallbladder and extra-hepatic bile ducts. Cases 2 and 3.
Chronic cholecystitis].
PMID- 25132440
TI - [Pathology of gallbladder and extrahepatic bile ducts. Case 4. Sclerosing
lymphoplasmacytic cholecystitis].
PMID- 25132441
TI - [Pathology of gallbladder and extrahepatic bile ducts. Case 5. Clear cell
vesicular adenocarcinoma, pT1bNx stage (TNM, 7th edition)].
PMID- 25132442
TI - [Pathology of gallbladder and extrahepatic bile ducts. Case 6. Well-
differentiated hilar cholangiocarcinoma pT2bN1].
PMID- 25132443
TI - [Pathology of gallbladder and extrahepatic bile ducts. Case 7. Biliary-type
tubulopapillary adenoma without dysplasia].
PMID- 25132444
TI - [Pathology of gallbladder and extrahepatic bile ducts. Case 8. Intraductal
papillary neoplasm of extrahepatic bile duct without invasive carcinoma (WHO
2010), with high-grade intraepithelial neoplasia/carcinoma in situ (pTisNx, TNM
7th edition): "Dysplastic degenerated biliary papillomatosis, but non-invasive"].
PMID- 25132445
TI - [A painful occipital mass revealing a posterior encephalocele].
AB - Encephalocele is a congenital malformation caused by a neural tube defect during
embryonic development. We report a case of posterior encephalocele in a 7-month
old infant with a painful occipital mass known since birth. Pathological
examination of the mass showed different mature tissues derived from the brain
and its coverings (e.g., neuroglia, ependymal canals and clusters of
meningothelial cells). A diagnosis of encephalocele was made. The different forms
of neural tube defect will be briefly discussed, especially the "aborted" forms
(e.g., non-specific midline mass lesion or angioma) that the pathologist may
encounter in his/her daily practice.
PMID- 25132446
TI - [Systemic EBV+ T-cell lymphoproliferative disease of childhood].
AB - Systemic EBV+ T-cell lymphoproliferative disease of childhood is a recent entity
described in the 2008 World Health Organisation tumours of haematopoietic system
and lymphoid tissues as a clonal T-cell EBV+ systemic proliferation. It occurs
after acute or chronic active EBV infection. We report the case of a caucasian,
immunocompetent 12-year-old girl, with no particular history, who presented with
hemophagocytic lymphohistiocytosis in the aftermath of an infectious
mononucleosis. Main symptoms were multiple organ failure, hepatosplenomegaly and
pancytopenia. Histopathology of peripheral lymph node and bone marrow revealed a
T-cell, CD8+, EBV+ lymphoproliferation. An elevated viral load was detected in
blood by PCR. The patient died within 3 weeks. Since most of the cases have been
reported in Asia and South America, few cases still have been described in
Europe. Unlike B-cell lymphoproliferation in immunocompromised individuals, T
cell EBV+ lymphoproliferation occurs in immunocompetent patients and seems to be
the consequence of a proliferative disorder of EBV-infected T-cells, attributed
to a cytotoxic T-cell response deficiency. These T-cell proliferations are more
frequently immunoreactive for CD8 than CD4. A key feature of the diagnosis might
be EBV viral load.
PMID- 25132447
TI - [An unusual renal arterial lesion].
PMID- 25132449
TI - Identification of putative kdr mutations in the tropical bed bug, Cimex
hemipterus (Hemiptera: Cimicidae).
AB - BACKGROUND: Bed bugs [both Cimex hemipterus (F.) and Cimex lectularius L.] are
highly resistant to pyrethroids worldwide. An important resistance mechanism
known as 'knockdown resistance' (kdr) is caused by genetic point mutations on the
voltage-gated sodium channel (VGSC) gene. Previous studies have identified two
point mutations (V419L and L925I) on the VGSC gene in C. lectularius that are
responsible for kdr-type resistance. However, the kdr mutations in C. hemipterus
have not been investigated. RESULTS: Four novel mutations, L899V (leucine to
valine), M918I (methionine to isoleucine), D953G (aspartic acid to glycine) and
L1014F (leucine to phenylalanine), were identified in the domain II region of the
C. hemipterus VGSC gene. This region has been widely investigated for the study
of kdr-type resistance to pyrethroids in other insect pests. The V419L and L925I
kdr mutations as previously identified in C. lectularius were not detected in C.
hemipterus. CONCLUSION: M918I and L1014F are considered to be probable kdr
mutations and may play essential roles in kdr-type resistance to pyrethroids in
C. hemipterus. Further studies are under way in the authors' laboratory to
determine the non-kdr-type resistance mechanisms in C. hemipterus.
PMID- 25132450
TI - Implementing skin-to-skin contact in the operating room following cesarean birth.
AB - Immediate skin-to-skin contact (SSC) after birth benefits the health of mothers
and newborns by increasing breastfeeding rates, stabilizing the newborn's
temperature, and encouraging bonding (Moore, Anderson, Bergman, & Dowswell,
2012). Although immediate SSC after a vaginal birth was common practice at our
hospital, it was rare in the operating room (OR) following a cesarean birth. To
address this practice problem, we conducted a project to evaluate the feasibility
of implementing SSC in the OR.
PMID- 25132448
TI - Mutations in NOTCH1 cause Adams-Oliver syndrome.
AB - Notch signaling determines and reinforces cell fate in bilaterally symmetric
multicellular eukaryotes. Despite the involvement of Notch in many key
developmental systems, human mutations in Notch signaling components have mainly
been described in disorders with vascular and bone effects. Here, we report five
heterozygous NOTCH1 variants in unrelated individuals with Adams-Oliver syndrome
(AOS), a rare disease with major features of aplasia cutis of the scalp and
terminal transverse limb defects. Using whole-genome sequencing in a cohort of 11
families lacking mutations in the four genes with known roles in AOS pathology
(ARHGAP31, RBPJ, DOCK6, and EOGT), we found a heterozygous de novo 85 kb deletion
spanning the NOTCH1 5' region and three coding variants (c.1285T>C [p.Cys429Arg],
c.4487G>A [p.Cys1496Tyr], and c.5965G>A [p.Asp1989Asn]), two of which are de
novo, in four unrelated probands. In a fifth family, we identified a heterozygous
canonical splice-site variant (c.743-1 G>T) in an affected father and daughter.
These variants were not present in 5,077 in-house control genomes or in public
databases. In keeping with the prominent developmental role described for Notch1
in mouse vasculature, we observed cardiac and multiple vascular defects in four
of the five families. We propose that the limb and scalp defects might also be
due to a vasculopathy in NOTCH1-related AOS. Our results suggest that mutations
in NOTCH1 are the most common cause of AOS and add to a growing list of human
diseases that have a vascular and/or bony component and are caused by alterations
in the Notch signaling pathway.
PMID- 25132451
TI - Development of a fluoride chronic effects benchmark for aquatic life in
freshwater.
AB - Canada has an interim water-quality guideline for fluoride for protection of
freshwater aquatic life that dates from 2002, and 1 Canadian province has a
different interim water-quality guideline for fluoride that dates to 1995. The
United States does not have a national benchmark for fluoride in freshwater, and
only 1 US state has such a benchmark. There are no other national or regional
benchmarks for fluoride chronic toxicity in freshwater. In the present study,
available data on the acute and chronic toxicity of fluoride to freshwater
aquatic life were compiled and reviewed. Acute toxicity was reported to occur at
concentrations ranging from 11.5 to >800 mg/L fluoride (F(-) ). The majority of
chronic effects occur at concentrations between 1.8 mg/L and 195 mg/L. A total of
10 chronic studies representing 16 species (5 fish, 7 invertebrates, and 4
algae/aquatic plants) were used to derive a chronic effects benchmark of 1.94
mg/L F(-) , applying the species sensitivity distribution approach.
PMID- 25132452
TI - A B-1a cell subset induces Foxp3(-) T cells with regulatory activity through an
IL-10-independent pathway.
AB - Regulatory T (Treg) cells play a critical role in the maintenance of tolerance. B
1a cells belong to a specific and functionally important B-cell subset that
exerts its regulatory role through the production of IL-10. While IL-10 has been
correlated with the induction of type 1 Treg (Tr1) cells or Tr1-like cells,
whether IL-10-producing B-1a cells are able to induce Treg cells, especially the
Tr1 lineage, is poorly understood. We have demonstrated that, similar to the
reported B-2 cells, B-1a cells are able to convert naive CD4(+)CD25(-) T cells
into a subset of T cells with suppressive function, which we called 'Treg-of-B1a'
cells. Treg-of-B1a cells do not express Foxp3, but upregulate the Treg markers
OX40, programmed death 1 (PD-1), inducible costimulator (ICOS) and IL-10R.
Moreover, Treg-of-B1a cells do not express Foxp3 and produce high levels of IFN
gamma and IL-10, but minimal amounts of IL-4; therefore, they resemble Tr1 cells.
However, utilizing IL-10(-/-) mice, we showed that IL-10 was not involved in the
induction of Treg-of-B1a cells. On the contrary, CD86-mediated costimulation was
essential for B-1a cells to drive the induction of Treg-of-B1a cells. Finally, we
demonstrated that, in contrast to the Treg cells generated by B-2 cells that
mediate contact-dependent suppression, Treg-of-B1a cells suppress through
secreting soluble factors. While Tr1 cells mediate suppression mainly through IL
10 or TGF-beta secretion, Treg-of-B1a cells mediate suppression through an IL-10-
and TGF-beta-independent pathway. Together, these findings suggest that B-1a
cells induce a functionally and phenotypically distinct Treg population that is
dissimilar to the reported Foxp3(+) Treg or Tr1 cells.
PMID- 25132453
TI - Adrenomedullin and endocrine control of immune cells during pregnancy.
AB - The immunology of pregnancy is complex and incompletely understood. Aberrant
immune activity in the decidua and in the placenta is believed to play a role in
diseases of pregnancy, such as infertility, miscarriage, fetal growth restriction
and preeclampsia. Here, we briefly review the endocrine control of uterine
natural killer cell populations and their functions by the peptide hormone
adrenomedullin. Studies in genetic animal models have revealed the critical
importance of adrenomedullin dosage at the maternal-fetal interface, with cells
from both the maternal and fetal compartments contributing to essential aspects
underlying appropriate uterine receptivity, implantation and vascular remodeling
of spiral arteries. These basic insights into the crosstalk between the endocrine
and immune systems within the maternal-fetal interface may ultimately translate
to a better understanding of the functions and consequences of dysregulated
adrenomedullin levels in clinically complicated pregnancies.
PMID- 25132455
TI - Practical knowledge of experienced nurses in critical care: a qualitative study
of their narratives.
AB - BACKGROUND: Scholars of nursing practices have claimed practical knowledge is
source of knowledge in its own right, nevertheless we know little about this
knowledge associated with day-to-day practice. The purpose of this study is to
describe knowledge that the more experienced nurses the in ICU make use of and
discover the components of care it includes. Understanding this knowledge can
contribute to improving the working practices of nurses with less experience.
METHODS: We used a phenomenologic and hermeneutic approach to conduct a
qualitative study. Open in-depth dialogue interviews were conducted with 13
experienced ICU nurses selected by intentional sampling. Data was compiled on
significant stories of their practice. The data analysis enabled units of meaning
to be categorised and grouped into topics regarding everyday practical knowledge.
RESULTS: Knowledge related to everyday practice was evaluated and grouped into
seven topics corresponding to how the ICU nurses understand their patient care:
1) Connecting with, calming and situating patients who cannot communicate; 2)
Situating and providing relief to patients in transitions of mechanical
respiration and non-invasive ventilation; 3) Providing reassurance and
guaranteeing the safety of immobilised patients; 4) The "connection" with
patients in comas; 5) Taking care of the body; 6) The transition from saving life
to palliative care; and 7) How to protect and defend the patient from errors. The
components of caretaking that guarantee success include: the calm, care and
affection with which they do things; the time devoted to understanding, situating
and comforting patients and families; and the commitment they take on with new
staff and doctors for the benefit of the patient. CONCLUSIONS: These results show
that stories of experiences describe a contextual practical knowledge that the
more experienced nurses develop as a natural and spontaneous response. In
critical patients the application of everyday practical knowledge greatly
influences their well-being. In those cases in which the nurses describe how they
have protected the patients from error, this practical knowledge can mean the
difference between life and death. The study highlights the need to manage
practical knowledge and undertake further research. The study is useful in
keeping clinical practice up-to-date.
PMID- 25132456
TI - Desiccation enhances phosphorylation of PSII and affects the distribution of
protein complexes in the thylakoid membrane.
AB - Desiccation has significant effects on photosynthetic processes in intertidal
macro-algae. We studied an intertidal macro-alga, Ulva sp., which can tolerate
desiccation, to investigate changes in photosynthetic performance and the
components and structure of thylakoid membrane proteins in response to
desiccation. Our results demonstrate that photosystem II (PSII) is more sensitive
to desiccation than photosystem I (PSI) in Ulva sp. Comparative proteomics of the
thylakoid membrane proteins at different levels of desiccation suggested that
there were few changes in the content of proteins involved in photosynthesis
during desiccation. Interestingly, we found that both the PSII subunit, PsbS
(Photosystem II S subunit) (a four-helix protein in the LHC superfamily), and
light-harvesting complex stress-related (LHCSR) proteins, which are required for
non-photochemical quenching in land plants and algae, respectively, were present
under both normal and desiccation conditions and both increased slightly during
desiccation. In addition, the results of immunoblot analysis suggested that the
phosphorylation of PSII and LHCII increases during desiccation. To investigate
further, we separated out a supercomplex formed during desiccation by blue native
polyacrylamide gel electrophoresis and identified the components by mass
spectrometry analysis. Our results show that phosphorylation of the complex
increases slightly with decreased water content. All the results suggest that
during the course of desiccation, few changes occur in the content of thylakoid
membrane proteins, but a rearrangement of the protein complex occurs in the
intertidal macro-alga Ulva sp.
PMID- 25132454
TI - The immunology of human cytomegalovirus latency: could latent infection be
cleared by novel immunotherapeutic strategies?
AB - While the host immune response following primary human cytomegalovirus (HCMV)
infection is generally effective at stopping virus replication and dissemination,
virus is never cleared by the host and like all herpesviruses, persists for life.
At least in part, this persistence is known to be facilitated by the ability of
HCMV to establish latency in myeloid cells in which infection is essentially
silent with, importantly, a total lack of new virus production. However, although
the viral transcription programme during latency is much suppressed, a number of
viral genes are expressed during latent infection at the protein level and many
of these have been shown to have profound effects on the latent cell and its
environment. Intriguingly, many of these latency-associated genes are also
expressed during lytic infection. Therefore, why the same potent host immune
responses generated during lytic infection to these viral gene products are not
recognized during latency, thereby allowing clearance of latently infected cells,
is far from clear. Reactivation from latency is also a major cause of HCMV
mediated disease, particularly in the immune compromised and immune naive, and is
also likely to be a major source of virus in chronic subclinical HCMV infection
which has been suggested to be associated with long-term diseases such as
atherosclerosis and some neoplasias. Consequently, understanding latency and why
latently infected cells appear to be immunoprivileged is crucial for an
understanding of the pathogenesis of HCMV and may help to design strategies to
eliminate latent virus reservoirs, at least in certain clinical settings.
PMID- 25132458
TI - Group-IV nanosheets with vacancies: a tight-binding extended Huckel study.
AB - In this work, we present a theoretical study of the electronic properties of
group-IV element nanosheets, namely graphene, silicene, germanene and the
corresponding hydrogenated structures for the two latter, silicane and germanane.
We compare the results of two different calculation methods, Density Functional
Theory (DFT) and Extended Huckel Theory (EHT), for both pristine sheets and
sheets of silicene and germanene with a single-atom vacancy. We show that EHT
offers a remarkably reliable description of the electronic structure of these
materials for all cases, thus offering an affordable way for studying large
systems for which DFT calculations would be expensive and lengthy.
PMID- 25132457
TI - Vitamin D deficiency decreases adiposity in rats and causes altered expression of
uncoupling proteins and steroid receptor coactivator3.
AB - The vitamin D endocrine system is functional in the adipose tissue, as
demonstrated in vitro, in cultured adipocytes, and in vivo in mutant mice that
developed altered lipid metabolism and fat storage in the absence of either 1,25
dihydroxyvitamin D3 [1,25(OH)2D3] or the vitamin D receptor. The aim of the
present study was to examine the role of vitamin D and calcium on body adiposity
in a diet-induced vitamin D deficient rat model. Vitamin D-deficient rats gained
less weight and had lower amounts of visceral fat. Consistent with reduced
adipose tissue mass, the vitamin D-deficient rats had low circulating levels of
leptin, which reflects body fat stores. Expression of vitamin D and calcium
sensing receptors, and that of genes involved in adipogenesis such as peroxisome
proliferator-activated receptor, fatty acid synthase and leptin were
significantly reduced in white adipose tissue of deficient rats compared to
vitamin D-sufficient rats. Furthermore, the expression of uncoupling proteins
(Ucp1 and Ucp2) was elevated in the white adipose tissue of the deficient rat
indicative of higher energy expenditure, thereby leading to a lean phenotype.
Expression of the p160 steroid receptor coactivator3 (SRC3), a key regulator of
adipogenesis in white adipose tissue was decreased in vitamin D-deficient state.
Interestingly, most of the changes observed in vitamin D deficient rats were
corrected by calcium supplementation alone. Our data demonstrates that dietary
vitamin D and calcium regulate adipose tissue function and metabolism.
PMID- 25132460
TI - Mapping support policies for informal carers across the European Union.
AB - BACKGROUND: At a time when health and social care services in European countries
are under pressure to contain or cut costs, informal carers are relied upon as
the main providers of long-term care. However, still little is known about the
availability of direct and indirect support for informal carers across the
European Union. METHODS: Primary data collection in all EU member states was
supplemented with an extensive review of the available literature. RESULTS:
Various forms and levels of support have been implemented across Europe to
facilitate the role of informal caregivers. Financial support is the most common
type of support provided, followed by respite care and training. Most countries
do not have a process in place to systematically identify informal carers and to
assess their needs. Policies are often at an early stage of development and the
breadth of support varies significantly across the EU. CONCLUSIONS: Policy
developments are uneven across the member states, with some countries having
mechanisms in place to assess the needs and support informal carers while others
are only starting to take an interest in developing support services. Given the
unprecedented challenges posed by population ageing, further research and better
data are needed to capture and monitor information on informal carers, to help
design adequate support policies and eventually to evaluate their impact across
the EU.
PMID- 25132459
TI - Intravenous infusion of paracetamol for intrapartum analgesia.
AB - AIM: To evaluate the efficacy and adverse effects of an i.v. infusion of
paracetamol during the active phase of labor as compared with sterile water
(placebo) as a method for intrapartum analgesia. METHODS: In a triple-blind,
randomized, placebo-controlled trial, 120 low-risk primiparous women presenting
in active labor at Ain Shams University Maternity Hospital, Cairo, Egypt, between
August 2011 and October 2012, were allocated to receive either 1000 mg i.v. of
paracetamol (n = 60) or sterile water (n = 60). The primary outcomes were the
efficacy of the drug to supply adequate analgesia as measured by a change in the
visual analog scale (VAS) pain intensity score at various time points after drug
administration and the need for additional rescue analgesia. The secondary
outcomes included the presence of adverse maternal or fetal events. RESULTS:
Compared to controls, i.v. infusion of paracetamol was associated with
significantly lower VAS score 15 and 30 min after the start of medication; also,
there was a significantly lower incidence of need for rescue medication (8/57
[14%] vs 49/59 [83.1%], P < 0.001) at 60 min after the start of medication. There
were no recorded maternal adverse effects in either group. There were no
differences in occurrence of intrapartum fetal distress or neonatal Apgar scores
between both groups. CONCLUSION: Paracetamol appears to be a safe and effective
medicine that can be used during the intrapartum period.
PMID- 25132461
TI - Is benzoyl peroxide 3% topical gel effective and safe in the treatment of acne
vulgaris in Japanese patients? A multicenter, randomized, double-blind, vehicle
controlled, parallel-group study.
AB - Benzoyl peroxide (BPO) as an anti-acne medication is not yet approved in Japan.
This study evaluated the efficacy and safety of a once-daily topical application
of BPO 3% gel versus an inert vehicle gel in Japanese acne patients. Three
hundred and sixty patients were randomized to receive BPO 3% or vehicle for 12
weeks. The primary efficacy end-point was absolute change in number of total
lesions (TL) from baseline to week 12 to demonstrate the superiority of BPO 3%
versus vehicle. Secondary efficacy end-points were absolute and percent change in
TL, inflammatory lesions (IL), non-inflammatory lesions (non-IL) and
Investigator's Static Global Assessment (ISGA). Change in TL counts from baseline
to week 12 for BPO 3% was superior to vehicle (difference, -21.0; P < 0.001).
Absolute and percent reductions in TL, IL and non-IL counts were greater for BPO
3% at all study visits. The proportion of patients with improvement in ISGA
scores was significantly higher with BPO 3% than with vehicle from week 2. All
adverse events were mild or moderate. Adverse drug-related reactions were higher
for BPO 3% (30%) than with vehicle (5%). Local tolerability scores of grade 1 or
more (slight to moderate) were more frequent with BPO 3% than vehicle with the
most significant differences observed in dryness (56% vs 27% at week 1-4),
peeling (19% vs 9% at week 1-2) and burning/stinging (58% vs 15% at week 1-12).
These results indicate that BPO 3% is effective while maintaining a favorable
safety and tolerability profile in Japanese acne patients.
PMID- 25132462
TI - Same-day discharge is feasible and safe in patients undergoing minimally invasive
staging for gynecologic malignancies.
AB - OBJECTIVE: The objective of the study was to evaluate the feasibility and safety
of same-day discharge of patients undergoing minimally invasive comprehensive
surgical staging for endometrial and cervical cancer. STUDY DESIGN: We performed
a retrospective review of consecutive patients from January 2008 to December 2011
undergoing comprehensive staging for endometrial or cervical cancer by
traditional laparoscopy or robotic-assisted laparoscopy and intended for same-day
discharge. Patients accomplishing same-day discharge were compared with those who
required admission. Clinical and demographic data, perioperative outcomes, and
postoperative patient contacts within 6 weeks were collected. Multivariate
logistic regression modeling was used to determine factors associated with
admission and unscheduled patient contacts within 2 weeks of surgery. RESULTS: A
total of 141 patients were identified. One hundred eighteen patients (83.7%)
underwent same-day discharge and 23 (16.3%) required overnight admission. The
variables that significantly predicted overnight admission were severe pain in
the postanesthesia care unit (odds ratio [OR], 6.81; 95% confidence interval
[CI], 1.74-26.6; P = .006), delayed ability to tolerate oral intake (OR, 9.3; 95%
CI, 2.25-38.6, P = .002), traditional laparoscopic vs robotic-assisted surgical
approach (OR, 9.05; 95% CI, 2.34-35.1; P = .001), and surgery start time at 2:00
pm or later (OR, 36.8; 95% CI, 6.19-219.3; P < .0001). There was no difference in
the readmission rate between patients undergoing same-day discharge compared with
overnight admission (11% vs 17%, P = .48). No variables significantly predicted
unscheduled patient contact within 2 weeks of surgery at P < .01. CONCLUSION:
Same-day discharge for patients undergoing laparoscopic or robotic-assisted
laparoscopic staging for endometrial or cervical cancer is feasible and safe.
There are low complication rates and few readmissions or unscheduled patient
contacts within 2 weeks of surgery.
PMID- 25132463
TI - Increased glucose and placental GLUT-1 in large infants of obese nondiabetic
mothers.
AB - OBJECTIVE: Obese women are at increased risk to deliver a large infant, however,
the underlying mechanisms are poorly understood. Fetal glucose availability is
critically dependent on placental transfer and is linked to fetal growth by
regulating the release of fetal growth hormones such as insulin. We hypothesized
that (1) umbilical vein glucose and insulin levels and (2) placental glucose
transporter (GLUT) expression and activity are positively correlated with early
pregnancy maternal body mass index and infant birthweight. STUDY DESIGN: Subjects
in this prospective observational cohort study were nondiabetic predominantly
Hispanic women delivered at term. Fasting maternal and umbilical vein glucose and
insulin concentrations were determined in 29 women with varying early pregnancy
body mass index (range, 18.0-54.3) who delivered infants with birthweights
ranging from 2800-4402 g. We isolated syncytiotrophoblast microvillous and basal
plasma membranes from 33 placentas and determined the expression of GLUT-1 and -9
(Western blot) and glucose uptake (radiolabeled glucose). RESULTS: Birthweight
was positively correlated with umbilical vein glucose and insulin and maternal
body mass index. Umbilical vein glucose levels were positively correlated with
placental weight and maternal body mass index, but not with maternal fasting
glucose. Basal plasma membranes GLUT-1 expression was positively correlated with
birthweight. In contrast, syncytiotrophoblast microvillous GLUT-1 and -9, basal
plasma membranes GLUT-9 expression and syncytiotrophoblast microvillous and basal
plasma membranes glucose transport activity were not correlated with birthweight.
CONCLUSION: Because maternal fasting glucose levels and placental glucose
transport capacity were not increased in obese women delivering larger infants,
we speculate that increased placental size promotes glucose delivery to these
fetuses.
PMID- 25132464
TI - Sonography-guided hydrostatic reduction of ileocolic intussusception in children:
analysis of failure and success in consecutive patients presenting timely to the
hospital.
AB - In children with ileocolic intussusception sonography is increasingly being used
for diagnosis, whereas fluoroscopy is frequently used for guiding non-invasive
reduction. This study assessed the success rate of radiation-free sonography
guided hydrostatic reduction in children with ileocolic intussusception, using
novel well-defined success rate indices. All children were evaluated who
presented from 2005 to 2013 to the local university hospital with ileocolic
intussusception. The patients were treated with sonography-guided hydrostatic
reduction unless primary surgery was clinically indicated. The according success
rate was determined by indices of Bekdash et al. They represent the ratio of
persistently successful non-surgical reductions versus four different
denominators, depending on including/excluding cases with primary surgery and
including/excluding cases requiring bowel resection/intervention. Fifty-six
consecutive patients were included (age, 3 months to 7.8 years). About 80% of the
patients presented until 24 h and 20% until 48 h after the onset of symptoms.
Seven patients underwent primary surgery, with bowel resection required in three
cases. Hydrostatic reduction was attempted in 49 patients, being permanently
successful in 41 cases (selective reduction rate 41/49 = 83.7%; crude reduction
rate 41/56 = 73.2%). The remaining eight patients underwent secondary surgery,
with just two patients not requiring surgical bowel resection/intervention
(corrected selective reduction rate 41/43 = 95.3%). The composite reduction rate
was 87.2% (successful/feasible reductions, 41/47). CONCLUSION: Radiation-free
sonography-guided hydrostatic reduction has a good success rate in children with
ileocolic intussusception. It may be particularly valuable in centers that are
already experienced with using sonography for the diagnosis.
PMID- 25132465
TI - Binding isotope effects as a tool for distinguishing hydrophobic and hydrophilic
binding sites of HIV-1 RT.
AB - The current treatment for HIV-1 infected patients consists of a cocktail of
inhibitors, in an attempt to improve the potency of the drugs by adding the
possible effects of each supplied compound. In this contribution, nine different
inhibitors of HIV-1 RT, one of the three key proteins responsible for the virus
replication, have been selected to develop and test a computational protocol that
allows getting a deep insight into the inhibitors' binding mechanism. The
interaction between the inhibitors and the protein have been quantified by
computing binding free energies through FEP calculations, while a more detailed
characterization of the kind of inhibitor-protein interactions is based on
frequency analysis of the ligands in the initial and final state, i.e. in
solution and binding the protein. QM/MM calculation of heavy atoms ((13)C, (15)N,
and (18)O) binding isotope effects (BIE) have been used to identify the binding
sites of the different inhibitors. Specific interactions between the isotopically
labeled atoms of the inhibitors and polar residues and magnesium cations on the
hydrophilic pocket of the protein are responsible for the frequencies shifting
that can be detected when comparing the IR spectra of the compounds in solution
and in the protein. On the contrary, it seems that changes in vdW interactions
from solution to the final state when the ligand is interacting with residues of
the hydrophobic cavity, does not influence frequency modes and then no BIE are
observed. Our results suggest that a proper computational protocol can be a
valuable tool which in turn can be used to increase the efficiency of anti AIDS
drugs.
PMID- 25132466
TI - Juvenile antioxidant treatment prevents adult deficits in a developmental model
of schizophrenia.
AB - Abnormal development can lead to deficits in adult brain function, a trajectory
likely underlying adolescent-onset psychiatric conditions such as schizophrenia.
Developmental manipulations yielding adult deficits in rodents provide an
opportunity to explore mechanisms involved in a delayed emergence of anomalies
driven by developmental alterations. Here we assessed whether oxidative stress
during presymptomatic stages causes adult anomalies in rats with a neonatal
ventral hippocampal lesion, a developmental rodent model useful for schizophrenia
research. Juvenile and adolescent treatment with the antioxidant N-acetyl
cysteine prevented the reduction of prefrontal parvalbumin interneuron activity
observed in this model, as well as electrophysiological and behavioral deficits
relevant to schizophrenia. Adolescent treatment with the glutathione peroxidase
mimic ebselen also reversed behavioral deficits in this animal model. These
findings suggest that presymptomatic oxidative stress yields abnormal adult brain
function in a developmentally compromised brain, and highlight redox modulation
as a potential target for early intervention.
PMID- 25132467
TI - A common structure underlies low-frequency cortical dynamics in movement, sleep,
and sedation.
AB - Upper-limb movements are often composed of regular submovements, and neural
correlates of submovement frequencies between 1 and 4 Hz have been found in the
motor cortex. The temporal profile of movements is usually assumed to be
determined by extrinsic factors such as limb biomechanics and feedback delays,
but another possibility is that an intrinsic rhythmicity contributes to low
frequencies in behavior. We used multielectrode recordings in monkeys performing
an isometric movement task to reveal cyclic activity in primary motor cortex
locked to submovements, and a distinct oscillation in premotor cortex. During
ketamine sedation and natural sleep, cortical activity traversed similar cycles
and became synchronized across areas. Because the same cortical dynamics are
coupled to submovements and also observed in the absence of behavior, we conclude
that the motor networks controlling the upper limb exhibit an intrinsic
periodicity at submovement frequencies that is reflected in the speed profile of
movements.
PMID- 25132469
TI - TNF and increased intracellular iron alter macrophage polarization to a
detrimental M1 phenotype in the injured spinal cord.
AB - Macrophages and microglia can be polarized along a continuum toward a detrimental
(M1) or a beneficial (M2) state in the injured CNS. Although phagocytosis of
myelin in vitro promotes M2 polarization, macrophage/microglia in the injured
spinal cord retain a predominantly M1 state that is detrimental to recovery. We
have identified two factors that underlie this skewing toward M1 polarization in
the injured CNS. We show that TNF prevents phagocytosis-mediated conversion from
M1 to M2 cells in vitro and in vivo in spinal cord injury (SCI). Additionally,
iron that accumulates in macrophages in SCI increases TNF expression and the
appearance of a macrophage population with a proinflammatory mixed M1/M2
phenotype. In addition, transplantation experiments show that increased loading
of M2 macrophages with iron induces a rapid switch from M2 to M1 phenotype. The
combined effect of this favors predominant and prolonged M1 macrophage
polarization that is detrimental to recovery after SCI.
PMID- 25132470
TI - Predictors of postoperative morbidity after laparoscopic versus open radical
hysterectomy plus external beam radiotherapy: a propensity-matched comparison.
AB - BACKGROUND: Identification of peri-operative variables predicting postoperative
morbidity may improve postoperative patients' care. We aimed to identify
patients' characteristics and operative factors predictive of early (<= 30-day)
and late (<= 6-month) morbidity in cervical cancer patients undergoing surgery
plus external beam radiotherapy (EBRT). METHODS: We studied 45 propensity-matched
patient pairs (90 patients) undergoing laparoscopic radical hysterectomy (LRH)
plus EBRT vs. abdominal radical hysterectomy (RAH) plus EBRT. Basic descriptive,
multivariable and artificial neuronal network analyses (ANN) were used to design
predicting models influencing outcomes. RESULTS: Baseline characteristics of the
study populations were similar. Patients undergoing LRH experienced lower blood
loss (200 (range, 10-700) vs. 400 (range, 100-2000) ml; P < 0.001), shorter
length of hospital stay (4 (range, 1-10) vs. 8 (range, 5-52) days; P < 0.001) and
similar operative time (235 (+/- 67.3) vs. 258 (+/- 70.2) min; P = 0.14) than
patients undergoing RAH. We observed that, at multivariate analysis, open
approach correlated with overall (OR: 1.2; 95%CI: 1.03-1.46), early (OR: 1.14;
95%CI:0.99-1.3) and late (OR: 1.13; 95%CI: 1.001-1.28) postoperative
complications. CONCLUSIONS: Open approach is the main predictor for developing
morbidity among cervical cancer patients undergoing radical hysterectomy followed
by adjuvant radiotherapy. Laparoscopic surgery enhances peri-operative surgical
results and minimizes the occurrence of late complications.
PMID- 25132471
TI - Systemic toxicity related to metal hip prostheses.
AB - INTRODUCTION: One in eight of all total hip replacements requires revision within
10 years, 60% because of wear-related complications. The bearing surfaces may be
made of cobalt/chromium, stainless steel, ceramic, or polyethylene. Friction
between bearing surfaces and corrosion of non-moving parts can result in
increased local and systemic metal concentrations. OBJECTIVES: To identify and
systematically review published reports of systemic toxicity attributed to metal
released from hip implants and to propose criteria for the assessment of these
patients. METHODS: Medline (from 1950) and Embase (from 1980) were searched to 28
February 2014 using the search terms (text/abstract) chrom* or cobalt* and
[toxic* or intox* or poison* or adverse effect or complication] and [prosthes* or
'joint replacement' or hip or arthroplast*] and PubMed (all available years) was
searched using the search term (("Chromium/adverse effects"[Mesh] OR
"Chromium/poisoning"[Mesh] OR "Chromium/toxicity"[Mesh]) OR ("Cobalt/adverse
effects"[Mesh] OR "Cobalt/poisoning"[Mesh] OR "Cobalt/toxicity"[Mesh])) AND
("Arthroplasty, Replacement, Hip"[Mesh] OR "Hip Prosthesis"[Mesh]). These
searches identified 281 unique references, of which 23 contained original case
data. Three further reports were identified from the bibliographies of these
papers. As some cases were reported repeatedly the 26 papers described only 18
individual cases. Systemic toxicity. Ten of these eighteen patients had undergone
revision from a ceramic-containing bearing to one containing a metal component.
The other eight had metal-on-metal prostheses. Systemic toxicity was first
manifest months and often several years after placement of the metal-containing
joint. The reported systemic features fell into three main categories: neuro
ocular toxicity (14 patients), cardiotoxicity (11 patients) and thyroid toxicity
(9 patients). Neurotoxicity was manifest as peripheral neuropathy (8 cases),
sensorineural hearing loss (7) and cognitive decline (5); ocular toxicity
presented as visual impairment (6). All these neurological features, except
cognitive decline, have been associated with cobalt poisoning previously. Type of
prosthesis and blood metal concentrations. Where blood or serum metal
concentrations were reported (n = 17 for cobalt and n = 14 for chromium), the
median cobalt concentration was 398 (range, 13.6-6521) MUg/L and the median
chromium concentration was 48 MUg/L (in whole blood) (range, 4.1-221 MUg/L
including serum and blood values). Those patients reported to have systemic
features who had received a metal-on-metal prosthesis (n = 8) had a median peak
blood cobalt concentration of 34.5 (range, 13.6-398.6) MUg/L; those with a metal
containing revision of a failed ceramic prosthesis (n = 10) had a median blood
cobalt concentration of 506 (range, 353-6521) MUg/L. Management. The most common
treatment was removal of the metal-containing prosthesis, undertaken in all but 2
patients. This was usually associated with a fall in circulating cobalt
concentration and improvement in some or all features. Clinical and toxicological
assessment of systemic features. We propose the following criteria for assessing
the likelihood that clinical features are related to cobalt toxicity: clinical
effects consistent with the known neurological, cardiac, or thyroidal effects of
cobalt, and for which any other explanation is less likely; increased blood
cobalt concentrations (substantially higher than those in patients with well
functioning prostheses) several months after hip replacement; a fall in the blood
cobalt concentration, usually accompanied by signs of improvement in features.
When judged by these criteria, the systemic features in 10 of the reported cases
are likely to be related to cobalt exposure from a metal-containing hip
prosthesis. CONCLUSIONS: Rarely, patients exposed to high circulating
concentrations of cobalt from failed hip replacements develop neurological
damage, hypothyroidism and/or cardiomyopathy, which may not resolve completely
even after removal of the prosthesis. The greatest risk of systemic cobalt
toxicity seems to result from accelerated wear of a cobalt-containing revision of
a failed ceramic prosthesis, rather than from primary failure of a metal-on-metal
prosthesis.
PMID- 25132468
TI - Discovery of a biomarker and lead small molecules to target r(GGGGCC)-associated
defects in c9FTD/ALS.
AB - A repeat expansion in C9ORF72 causes frontotemporal dementia and amyotrophic
lateral sclerosis (c9FTD/ALS). RNA of the expanded repeat (r(GGGGCC)exp) forms
nuclear foci or undergoes repeat-associated non-ATG (RAN) translation, producing
"c9RAN proteins." Since neutralizing r(GGGGCC)exp could inhibit these potentially
toxic events, we sought to identify small-molecule binders of r(GGGGCC)exp.
Chemical and enzymatic probing of r(GGGGCC)8 indicate that it adopts a hairpin
structure in equilibrium with a quadruplex structure. Using this model, bioactive
small molecules targeting r(GGGGCC)exp were designed and found to significantly
inhibit RAN translation and foci formation in cultured cells expressing
r(GGGGCC)66 and neurons transdifferentiated from fibroblasts of repeat expansion
carriers. Finally, we show that poly(GP) c9RAN proteins are specifically detected
in c9ALS patient cerebrospinal fluid. Our findings highlight r(GGGGCC)exp-binding
small molecules as a possible c9FTD/ALS therapeutic and suggest that c9RAN
proteins could potentially serve as a pharmacodynamic biomarker to assess
efficacy of therapies that target r(GGGGCC)exp.
PMID- 25132473
TI - Local lay rescuers with AEDs, alerted by text messages, contribute to early
defibrillation in a Dutch out-of-hospital cardiac arrest dispatch system.
AB - AIM: Public access defibrillation rarely reaches out-of-hospital cardiac arrest
(OHCA) patients in residential areas. We developed a text message (TM) alert
system, dispatching local lay rescuers (TM-responders). We analyzed the
functioning of this system, focusing on response times and early defibrillation
in relation to other responders. METHODS: In July 2013, 14112 TM-responders and
1550 automated external defibrillators (AEDs) were registered in a database
residing with the dispatch center of two regions of the Netherlands. TM
responders living <1000m radius of the patient received a TM to go to the patient
directly, or were directed to retrieve an AED first. We analyzed 1536 OHCA
patients where a defibrillator was connected from February 2010 until July 2013.
Electrocardiograms from all defibrillators were analyzed for connection and
defibrillation time. RESULTS: Of all OHCAs, the dispatcher activated the TM-alert
system 893 times (58.1%). In 850 cases >=1 TM-responder received a TM-alert and
in 738 cases >=1 AED was available. A TM-responder AED was connected in 184 of
all OHCAs (12.0%), corresponding with 23.1% of all connected AEDs. Of all used TM
responder AEDs, 87.5% were used in residential areas, compared to 71.6% of all
other defibrillators. TM-responders with AEDs defibrillated mean 2:39 (min:sec)
earlier compared to emergency medical services (median interval 8:00 [25-75th
percentile, 6:35-9:49] vs. 10:39 [25-75th percentile, 8:18-13:23], P<0.001). Of
all shocking TM-responder AEDs, 10.5% delivered a shock <=6min after call.
CONCLUSION: A TM-alert system that includes local lay rescuers and AEDs
contributes to earlier defibrillation in OHCA, particularly in residential areas.
PMID- 25132474
TI - EuReCa ONE - ONE month - ONE Europe - ONE goal.
PMID- 25132472
TI - Lymphatic fate specification: an ERK-controlled transcriptional program.
AB - Lymphatic vessels are intimately involved in the regulation of water and solute
homeostasis by returning interstitial fluid back to the venous circulation and
play an equally important role in immune responses by providing avenues for
immune cell transport. Defects in the lymphatic vasculature result in a number of
pathological conditions, including lymphedema and lymphangiectasia. Knowledge of
molecular mechanisms underlying lymphatic development and maintenance is
therefore critical for understanding, prevention and treatment of lymphatic
circulation-related diseases. Research in the past two decades has uncovered
several key transcriptional factors (Prox1, Sox18 and Coup-TFII) controlling
lymphatic fate specification. Most recently, ERK signaling has emerged as a
critical regulator of this transcriptional program. This review summarizes our
current understanding of lymphatic fate determination and its transcriptional
controls.
PMID- 25132475
TI - Therapeutic temperature management after cardiac arrest and the risk of bleeding:
systematic review and meta-analysis.
AB - AIM: Prognosis after cardiac arrest in the era of modern critical care is still
poor with a high mortality of approximately 90%. Around 30% of the survivors have
neurological impairments. Targeted temperature management (TTM) is the only
treatment option which can improve mortality and neurological outcome. It is so
far unclear if bleeding complications occur more often in patients undergoing TTM
treatment. METHODS: We conducted a systematic literature research in September
2013 including three major databases i.e. MEDLINE, EMBASE and CENTRAL. All
studies were rated in respect to the ILCOR Guidelines and concerning their level
of evidence and quality. We then performed a meta-analysis on bleeding
disposition under TTM. RESULTS: We initially found 941 studies out of which 34
matched our requirements and were thus included in our overview. Five studies
including 599 patients were summarized in a meta-analysis concerning bleeding
complications of all severities. There was a trend toward higher bleeding in
patients treated with TTM (RR: 1.30, 95% CI: 0.97-1.74) which did not reach
significance (p=0.085). Seven studies with an overall 599 patients were included
in our meta-analysis on bleeding requiring transfusion. There was no significant
difference in the incidence of severe bleeding with a risk ratio of 0.97 (95% CI:
0.61-1.56, p=0.909). CONCLUSIONS: The data included in our meta-analysis indicate
that, concerning the risk of bleeding, TTM is a safe method for patients after
cardiac arrest. We did not observe a significantly higher risk for bleeding in
patients undergoing TTM.
PMID- 25132476
TI - Reply to Letter: Adrenaline in out-of hospital cardiac arrest.
PMID- 25132477
TI - Real-time video communication improves provider performance in a simulated
neonatal resuscitation.
AB - AIM: To determine if a real-time audiovisual link with a neonatologist, termed
video-assisted resuscitation or VAR, improves provider performance during a
simulated neonatal resuscitation scenario. METHODS: Using high-fidelity
simulation, 46 study participants were presented with a neonatal resuscitation
scenario. The control group performed independently, while the intervention group
utilized VAR. Time to effective ventilation was compared using Wilcoxon rank sum
tests. Providers' use of the corrective steps for ineffective ventilation per the
NRP algorithm was compared using Cochran-Armitage trend tests. RESULTS: The time
needed to establish effective ventilation was significantly reduced in the
intervention group when compared to the control group (mean time 2 min 42 s
versus 4 min 11 s, p<0.001). In the setting of ineffective ventilation, only 35%
of control subjects used three or more of the first five corrective steps and
none of them used all five steps. Providers in the control group most frequently
neglected to open the mouth and increase positive pressure. In contrast, all of
those in the intervention group used all of the first five corrective steps,
p<0.001. All participants in the control group decided to intubate the infant to
establish effective ventilation, compared to none in the intervention group,
p<0.001. CONCLUSION: Using VAR during a simulated neonatal resuscitation scenario
significantly reduces the time to establish effective ventilation and improves
provider adherence to NRP guidelines. This technology may be a means for regional
centers to support local providers during a neonatal emergency to improve patient
safety and improve neonatal outcomes.
PMID- 25132478
TI - Rhythm not ST elevation may be the key for post-resuscitation therapeutic
success.
PMID- 25132479
TI - Adrenaline in out-of hospital cardiac arrest.
PMID- 25132480
TI - BRAF mutation testing in solid tumors: a methodological comparison.
AB - Solid tumor genotyping has become standard of care for the characterization of
proto-oncogene mutational status, which has traditionally been accomplished with
Sanger sequencing. However, companion diagnostic assays and comparable laboratory
developed tests are becoming increasingly popular, such as the cobas 4800 BRAF
V600 Mutation Test and the INFINITI KRAS-BRAF assay, respectively. This study
evaluates and validates the analytical performance of the INFINITI KRAS-BRAF
assay and compares concordance of BRAF status with two reference assays, the
cobas test and Sanger sequencing. DNA extraction from FFPE tissue specimens was
performed followed by multiplex PCR amplification and fluorescent label
incorporation using allele-specific primer extension. Hybridization to a
microarray, signal detection, and analysis were then performed. The limits of
detection were determined by testing dilutions of mutant BRAF alleles within wild
type background DNA, and accuracy was calculated based on these results. The
INFINITI KRAS-BRAF assay produced 100% concordance with the cobas test and Sanger
sequencing and had sensitivity equivalent to the cobas assay. The INFINITI assay
is repeatable with at least 95% accuracy in the detection of mutant and wild-type
BRAF alleles. These results confirm that the INFINITI KRAS-BRAF assay is
comparable to traditional sequencing and the Food and Drug Administration
approved companion diagnostic assay for the detection of BRAF mutations.
PMID- 25132483
TI - Postsacral vertebral morphology in relation to tail length among primates and
other mammals.
AB - Tail reduction/loss independently evolved in a number of mammalian lineages,
including hominoid primates. One prerequisite to appropriately contextualizing
its occurrence and understanding its significance is the ability to track
evolutionary changes in tail length throughout the fossil record. However, to
date, the bony correlates of tail length variation among living taxa have not
been comprehensively examined. This study quantifies postsacral vertebral
morphology among living primates and other mammals known to differ in relative
tail length (RTL). Linear and angular measurements with known biomechanical
significance were collected on the first, mid-, and transition proximal
postsacral vertebrae, and their relationship with RTL was assessed using
phylogenetic generalized least-squares regression methods. Compared to shorter
tailed primates, longer-tailed primates possess a greater number of postsacral
vertebral features associated with increased proximal tail flexibility (e.g.,
craniocaudally longer vertebral bodies), increased intervertebral body joint
range of motion (e.g., more circularly shaped cranial articular surfaces), and
increased leverage of tail musculature (e.g., longer spinous processes). These
observations are corroborated by the comparative mammalian sample, which shows
that distantly related short-tailed (e.g., Phascolarctos, Lynx) and long-tailed
(e.g., Dendrolagus, Acinonyx) nonprimate mammals morphologically converge with
short-tailed (e.g., Macaca tonkeana) and long-tailed (e.g., Macaca fascicularis)
primates, respectively. Multivariate models demonstrate that the variables
examined account for 70% (all mammals) to 94% (only primates) of the variance in
RTL. Results of this study may be used to infer the tail lengths of extinct
primates and other mammals, thereby improving our understanding about the
evolution of tail reduction/loss.
PMID- 25132482
TI - Real-time assessment of hybridization between wolves and dogs: combining
noninvasive samples with ancestry informative markers.
AB - Wolves and dogs provide a paradigmatic example of the ecological and conservation
implications of hybridization events between wild and domesticated forms.
However, our understanding of such implications has been traditionally hampered
by both high genetic similarity and the difficulties in obtaining tissue samples
(TS), which limit our ability to assess ongoing hybridization events. To assess
the occurrence and extension of hybridization in a pack of wolf-dog hybrids in
northwestern Iberia, we compared the power of 52 nuclear markers implemented on
TS with a subset of 13 ancestry informative markers (AIMs) typed in noninvasive
samples (NIS). We demonstrate that the 13 AIMs are as accurate as the 52 markers
that were chosen without regard to the power to differentiate between wolves and
dogs, also having the advantage of being rapidly screened on NIS. The efficiency
of AIMs significantly outperformed ten random sets of similar size and an
additional commercial set of 18 markers. Bayesian clustering analysis implemented
on AIMs and NIS identified nine hybrids, two wolves and two dogs. Four hybrids
were unambiguously assigned to F1xWolf backcrosses. Our approach (AIMs + NIS)
overcomes previous difficulties related to sample availability and informative
power of markers, allowing a quick identification of wolf-dog hybrids in the
first phases of hybridization episodes. This provides managers with a reliable
tool to evaluate hybridization and estimate the success of their actions. This
approach may be easily adapted for other pairs of wild/domesticated species, thus
improving our understanding of the introgression of domestication genes into
natural populations.
PMID- 25132481
TI - Haplotype counting by next-generation sequencing for ultrasensitive human DNA
detection.
AB - Human identity testing is critical to the fields of forensics, paternity, and
hematopoietic stem cell transplantation. Most bone marrow (BM) engraftment
testing currently uses microsatellites or short tandem repeats that are resolved
by capillary electrophoresis. Single-nucleotide polymorphisms (SNPs) are
theoretically a better choice among polymorphic DNA; however, ultrasensitive
detection of SNPs using next-generation sequencing is currently not possible
because of its inherently high error rate. We circumvent this problem by
analyzing blocks of closely spaced SNPs, or haplotypes. As proof-of-principle, we
chose the HLA-A locus because it is highly polymorphic and is already genotyped
to select proper donors for BM transplant recipients. We aligned common HLA-A
alleles and identified a region containing 18 closely spaced SNPs, flanked by
nonpolymorphic DNA for primer placement. Analysis of cell line mixtures shows
that the assay is accurate and precise, and has a lower limit of detection of
approximately 0.01%. The BM from a series of hematopoietic stem cell
transplantation patients who tested as all donor by short tandem repeat analysis
demonstrated 0% to 1.5% patient DNA. Comprehensive analysis of the human genome
using the 1000 Genomes database identified many additional loci that could be
used for this purpose. This assay may prove useful to identify hematopoietic stem
cell transplantation patients destined to relapse, microchimerism associated with
solid organ transplantation, forensic applications, and possibly patient
identification.
PMID- 25132484
TI - Immune thrombocytopenia and alopecia areata: spontaneous occurrence and
resolution in the same patient.
AB - Alopecia areata (AA) and immune thrombocytopenia (ITP) are autoimmune conditions
occasionally encountered by pediatricians, but their simultaneous occurrence is
rare. We describe here a 7-year-old female who acutely developed both AA and ITP.
Within 3 months both conditions resolved spontaneously, suggesting a
pathophysiologic relationship.
PMID- 25132485
TI - Water and temperature relations of soil Actinobacteria.
AB - Actinobacteria perform essential functions within soils, and are dependent on
available water to do so. We determined the water-activity (aw ) limits for cell
division of Streptomyces albidoflavus, Streptomyces rectiviolaceus,
Micromonospora grisea and Micromonospora (JCM 3050) over a range of temperatures,
using culture media supplemented with a biologically permissive solute
(glycerol). Each species grew optimally at 0.998 aw (control; no added glycerol)
and growth rates were near-optimal in the range 0.971-0.974 (1 M glycerol) at
permissive temperatures. Each was capable of cell division at 0.916-0.924 aw (2 M
glycerol), but only S. albidoflavus grew at 0.895 or 0.897 aw (3 M glycerol, at
30 and 37 degrees C respectively). For S. albidoflavus, however, no growth
occurred on media at <= 0.870 (4 M glycerol) during the 40-day assessment period,
regardless of temperature, and a theoretical limit of 0.877 aw was derived by
extrapolation of growth curves. This level of solute tolerance is high for non
halophilic bacteria, but is consistent with reported limits for the growth and
metabolic activities of soil microbes. The limit, within the range 0.895-0.870 aw
, is very much inferior to those for obligately halophilic bacteria and extremely
halophilic or xerophilic fungi, and is inconsistent with earlier reports of cell
division at 0.500 aw . These findings are discussed in relation to planetary
protection policy for space exploration and the microbiology of arid soils.
PMID- 25132486
TI - Reply: Should we encourage exercise and sports in children and adolescents with
cancer?
PMID- 25132487
TI - Health governance in India: citizenship as situated practice.
AB - Despite the impressive growth of the Indian economy over the past decades, the
country struggles to deal with multiple and overlapping forms of inequality. One
of the Indian government's main policy responses to this situation has been an
increasing engagement with the 'rights regime', witnessed by the formulation of a
plethora of rights-based laws as policy instruments. Important among these are
the National Rural Health Mission (NRHM). Grounded in ethnographic research in
Rajasthan focused on the management of maternal and child health under NRHM, this
paper demonstrates how women, as mothers and health workers, organise themselves
in relation to rights and identities. I argue that the rights of citizenship are
not solely contingent upon the existence of legally guaranteed rights but also
significantly on the social conditions that make their effective exercise
possible. This implies that while citizenship is in one sense a membership status
that entails a package of rights, duties, and obligations as well as equality,
justice, and autonomy, its development and nature can only be understood through
a careful consideration and analysis of contextually specific social conditions.
PMID- 25132488
TI - Characterization of overt and occult hepatitis B virus infection among HTLV-1
positive healthy carriers in the Northeast of Iran; AN HTLV-I endemic area.
AB - To date, no studies have provided data on hepatitis B virus (HBV) prevalence
among asymptomatic, healthy human T-lymphotropic virus (HTLV-I) positive
carriers. This sero- and molecular epidemiology study was performed on patients
in the Northeast of Iran, which is an endemic area for HTLV-I infection. A total
of 109 sera were collected from HTLV-I positive healthy carriers who were
admitted to Ghaem Hospital, Mashhad City. All were tested for HBV serology and
subsequently, real time PCR was carried out on the samples, regardless of the
results of the serology. Standard PCR and direct sequencing were applied on
positive samples. All cases were negative for HBsAg, Anti-HBc, and anti-HBs were
positive in 34 (31.1%), and 35 (32%) individuals, respectively. There were 19
(17.4%) cases that were positive only for anti-HBs, and they had already received
HBV vaccine. 16 (15%) were positive for both anti-HBs and anti-HBc, indicating a
past-resolved HBV infection. 18 (16.5%) were isolated as anti-HBc, and 56 (51.3%)
were negative for all HBV serological markers. Only one subject (0.9%) had
detectable HBV DNA (2153 copy/ml), and assigned as being an occult HBV infection.
The low prevalence of HBsAg, despite the high percentage of anti-HBc positive
cases, might be related to the suppression effect of HTLV-I on surface protein
expression. The low prevalence of HBV infection among HTLV-I positive healthy
carriers from an endemic region, indicates that the epidemiology of HTLV-I and
HBV coinfection is related to the endemicity of HBV in that region, rather than
HTLV-I endemicity.
PMID- 25132489
TI - Identification and functional characterization of a sulfate transporter induced
by both sulfur starvation and mycorrhiza formation in Lotus japonicus.
AB - Arbuscular mycorrhizas (AMs) are one of the most widespread symbioses in the
world. They allow plants to receive mineral nutrients from the symbiotic fungus
which in turn gets back up to 20% of plant carbon and completes its life cycle.
Especially in low-nutrient conditions, AM fungi are capable of significantly
improving plant phosphate and nitrogen acquisition, but fewer data are available
about sulfur (S) nutrition. We focused on S metabolism in Lotus japonicus upon
mycorrhizal colonization under sulfur starvation or repletion. We investigated
both tissue sulfate concentrations and S-related gene expression, at cell-type or
whole-organ level. Gene expression and sulfate tissue concentration showed that
Rhizophagus irregularis colonization can improve plant S nutritional status under
S starvation. A group 1 sulfate transporter, LjSultr1;2, induced by both S
starvation and mycorrhiza formation, was identified. Its transcript was localized
in arbuscule-containing cells, which was confirmed with a promoter-GUS assay, and
its function was verified through phenotyping of TILLING mutants in
nonmycorrhizal seedlings. LjSultr1;2 thus appears to encode a key protein
involved in plant sulfate uptake. In contrast to phosphate transporters, a single
gene, LjSultr1;2, seems to mediate both direct and symbiotic pathways of S uptake
in L. japonicus.
PMID- 25132490
TI - Time since onset of walking predicts tibial bone strength in early childhood.
AB - Bone strength in adulthood is known to be affected by health at birth and early
childhood. Habitual bone loading is a primary determinant of bone strength in
later childhood and adulthood. However, the effects of physical activity in early
childhood (e.g. crawling, standing and walking) on bone strength are unknown.
Fifty-three children (twenty-seven males) were included in a longitudinal study
in their early infancy. Shortly after birth (0.3+/-0.3months), details of mass
and height were obtained along with a pQCT scan at 20% distal-proximal tibia
length. At 14.8+/-0.5months of age the same data were collected, along with
details of age at onset of standing, crawling, supported and unsupported walking.
Time since onset of walking unsupported was associated with greater bone mass,
cortical bone area, pericortical circumference and polar moment of inertia of
both total and cortical bone (all P<0.05). There were no significant associations
between other physical activity timepoints and bone measures. Age at onset of
walking was not significantly related to mass, length or bone measures at birth.
The results suggest that time since attainment of independent walking -
representing exposure of the tibia to the large reaction and muscular forces
associated with locomotion - is a primary determinant of bone strength in early
childhood. This finding raises the possible opportunity of physical activity
interventions at young age in paediatric populations associated with low
childhood bone strength and late walking (e.g. low birth weight, cerebral palsy
and Down's Syndrome, etc.).
PMID- 25132492
TI - An in vitro biomechanical comparison of hydroxyapatite coated and uncoated ao
cortical bone screws for a limited contact: dynamic compression plate fixation of
osteotomized equine 3rd metacarpal bones.
AB - OBJECTIVES: To compare the monotonic biomechanical properties of a broad 4.5 mm
limited contact-dynamic compression plate (LC-DCP) fixation secured with
hydroxyapatite (HA) coated cortical bone screws (HA-LC-DCP) versus uncoated
cortical bone screws (AO-LC-DCP) to repair osteotomized equine 3rd metacarpal
(MC3) bones. STUDY DESIGN: Experimental. SAMPLE POPULATION: Adult equine
cadaveric MC3 bones (n = 12 pair). METHODS: Twelve pairs of equine MC3 were
divided into 3 test groups (4 pairs each) for: (1) 4 point bending single cycle
to failure testing; (2) 4 point bending cyclic fatigue testing; and (3) torsional
single cycle to failure testing. For the HA-LC-DCP-MC3 construct, an 8-hole broad
LC-DCP (Synthes Ltd, Paoli, PA) was secured on the dorsal surface of each
randomly selected MC3 bone with a combination of four 5.5 mm and four 4.5 mm HA
coated cortical screws. For the AO-LC-DCP-MC3 construct, an 8-hole 4.5 mm broad
LC-DCP was secured on the dorsal surface of the contralateral MC3 bone with a
combination of four 5.5 mm and four 4.5 mm uncoated cortical screws. All MC3
bones had mid-diaphyseal osteotomies. Mean test variable values for each method
were compared using a paired t-test within each group. Significance was set at P
< .05. RESULTS: Mean yield load, yield bending moment, composite rigidity,
failure load, and failure bending moment, under 4 point bending, single cycle to
failure, of the HA-LC-DCP fixation were significantly greater than those of the
AO-LC-DCP fixation. Mean +/- SD values for the HA-LC-DCP and the AO-LC-DCP
fixation techniques, respectively, in single cycle to failure under 4 point
bending were: yield load, 26.7 +/- 2.15 and 16.3 +/- 1.38 kN; yield bending
moment, 527.4 +/- 42.4 and 322.9 +/- 27.2 N-m; composite rigidity, 5306 +/- 399
and 3003 +/- 300 N-m/rad; failure load, 40.6 +/- 3.94 and 26.5 +/- 2.52 kN; and
failure bending moment, 801.9 +/- 77.9 and 522.9 +/- 52.2 N-m. Mean cycles to
failure in 4 point bending of the HA-LC-DCP fixation (116,274 +/- 13,211) was
significantly greater than that of the AO-LC-DCP fixation 47,619 +/- 6580. Mean
yield load, mean composite rigidity, and mean failure load under torsional
testing, single cycle to failure was significantly greater for the broad HA-LC
DCP fixation compared with the AO-LC-DCP fixation. In single cycle to failure
under torsion, mean +/- SD values for the HA-LC-DCP and the AO-LC-DCP fixation
techniques, respectively, were: yield load, 101.3 +/- 14.68 and 70.54 +/- 10.20 N
m; composite rigidity, 437.9 +/- 32.9 and 220.7 +/- 17.6 N-m/rad; and failure
load: 105.7 +/- 15.5 and 75.28 +/- 10.1 N-m. CONCLUSION: HA-LC-DCP was superior
to AO-LC-DCP in resisting the static overload forces (palmarodorsal 4 point
bending and torsional) and in resisting cyclic fatigue under palmarodorsal 4
point bending.
PMID- 25132493
TI - Graphene on mica - intercalated water trapped for life.
AB - In this work we study the effect of thermal processing of exfoliated graphene on
mica with respect to changes in graphene morphology and surface potential. Mild
annealing to temperatures of about 200 degrees C leads to the removal of small
amounts of intercalated water at graphene edges. By heating to 600 degrees C the
areas without intercalated water are substantially increased enabling a
quantification of the charge transfer properties of the water layer by locally
resolved Kelvin probe force microscopy data. A complete removal on a global scale
cannot be achieved because mica begins to decompose at temperatures above 600
degrees C. By correlating Kelvin probe force microscopy and Raman spectroscopy
maps we find a transition from p-type to n-type doping of graphene during thermal
processing which is driven by the dehydration of the mica substrate and an
accumulation of defects in the graphene sheet.
PMID- 25132494
TI - Optimization of ultrasound-assisted extraction of polyphenols from spruce wood
bark.
AB - Here we describe the ultrasound-assisted extraction of the phenolic compounds
from spruce wood bark and present a straight-forward experimental planning
method, allowing the optimisation of the process. The effect of ethanol
concentration, temperature and extraction time were evaluated through a 3(2).2
experimental planning. The efficiency of the extraction process was appreciated
based on factorial ANOVA results. The maximum extraction yield of total
polyphenols (13.232mg gallic acid equivalents (GAE)/g of spruce bark tested) was
obtained using a process time of 60min, an extraction temperature of 54 degrees C
and a concentration of ethanol of 70% respectively. These results indicate that
an important quantity of bioactive compounds can be extracted from spruce wood
bark by ultrasound assisted extraction technology.
PMID- 25132495
TI - Decolorization of azo dye Orange G by aluminum powder enhanced by ultrasonic
irradiation.
AB - In this work, the decolorization of azo dye Orange G (OG) in aqueous solution by
aluminum powder enhanced by ultrasonic irradiation (AlP-UI) was investigated. The
effects of various operating operational parameters such as the initial pH,
initial OG concentration, AlP dosage, ultrasound power and added hydrogen
peroxide (H2O2) concentration were studied. The results showed that the
decolorization rate was enhanced when the aqueous OG was irradiated
simultaneously by ultrasound in the AlP-acid systems. The decolorization rate
decreased with the increase of both initial pH values of 2.0-4.0 and OG initial
concentrations of 10-80mg/L, increased with the ultrasound power enhancing from
500 to 900W. An optimum value was reached at 2.0g/L of the AlP dosage in the
range of 0.5-2.5g/L. The decolorization rate enhanced significantly by the
addition of hydrogen peroxide in the range of 10-100mM to AlP-UI system reached
an optimum value of 0.1491min(-1). The decolorization of OG appears to involve
primarily oxidative steps, the cleavage of NN bond, which were verificated by the
intermediate products of OG under the optimal tested degradation system, aniline
and 1-amino-2-naphthol-6,8-disulfonate detected by the LC-MS.
PMID- 25132496
TI - ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC
development.
AB - Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of
viral hepatitis, insulin resistance, hepatosteatosis, and nonalcoholic
steatohepatitis (NASH), disorders that increase risk of hepatocellular carcinoma
(HCC). To determine whether and how ER stress contributes to obesity-driven
hepatic tumorigenesis we fed wild-type (WT) and MUP-uPA mice, in which hepatocyte
ER stress is induced by plasminogen activator expression, with high-fat diet.
Although both strains were equally insulin resistant, the MUP-uPA mice exhibited
more liver damage, more immune infiltration, and increased lipogenesis and, as a
result, displayed classical NASH signs and developed typical steatohepatitic HCC.
Both NASH and HCC development were dependent on TNF produced by inflammatory
macrophages that accumulate in the MUP-uPA liver in response to hepatocyte ER
stress.
PMID- 25132498
TI - Stem cell therapy for glaucoma: science or snake oil?
AB - In recent years there has been substantial progress in developing stem cell
treatments for glaucoma. As a downstream approach that targets the underlying
susceptibility of retinal ganglion and trabecular meshwork cells, stem cell
therapy has the potential to both replace lost, and protect damaged, cells by
secreting neurotrophic factors. A variety of sources, including embryonic cells,
adult cells derived from the central nervous system, and induced pluripotent stem
cells show promise as therapeutic approaches. Even though safety concerns and
ethical controversies have limited clinical implementation, some institutions
have already commercialized stem cell therapy and are using direct-to-consumer
advertising to attract patients with glaucoma. We review the progress of stem
cell therapy and its current commercial availability.
PMID- 25132499
TI - To What did They Consent? Understanding Consent Among Low Literacy Participants
in a Microbicide Feasibility Study in Mazabuka, Zambia.
AB - We conducted a study to review the consenting process in a vaginal microbicide
feasibility study conducted in Mazabuka, Zambia. Participants were drawn from
those participating in the microbicide study. A questionnaire and focus group
discussion were used to collect information on participants' understanding of
study aims, risks and benefits. Altogether, 200 participants took part in this
study. The results of the study showed that while all participants signed or
endorsed their thumbprints to the consent forms, full informed consent was not
attained from most of the participants since 77% (n = 154) of the participants
had numerous questions about the study and 34% (n = 68) did not know who to get
in touch with concerning the study. Study objectives were not fully understood by
over 61% of the participants. Sixty four percent of the participants were not
sure of the risks of taking part in the microbicide study. A significant number
thought the study was all about determining their HIV status. Some participants
were concerned that their partners were not on the trial as they were convinced
that being on the study meant that that they had a lifetime protection from HIV
infection. The process of obtaining consent was inadequate as various phases of
the study were not fully understood. We recommend the need for researchers to
reinforce the consenting process in all studies and more so when studies are
conducted in low literacy populations.
PMID- 25132497
TI - BCR-ABL1 compound mutations combining key kinase domain positions confer clinical
resistance to ponatinib in Ph chromosome-positive leukemia.
AB - Ponatinib is the only currently approved tyrosine kinase inhibitor (TKI) that
suppresses all BCR-ABL1 single mutants in Philadelphia chromosome-positive
(Ph(+)) leukemia, including the recalcitrant BCR-ABL1(T315I) mutant. However,
emergence of compound mutations in a BCR-ABL1 allele may confer ponatinib
resistance. We found that clinically reported BCR-ABL1 compound mutants center on
12 key positions and confer varying resistance to imatinib, nilotinib, dasatinib,
ponatinib, rebastinib, and bosutinib. T315I-inclusive compound mutants confer
high-level resistance to TKIs, including ponatinib. In vitro resistance profiling
was predictive of treatment outcomes in Ph(+) leukemia patients. Structural
explanations for compound mutation-based resistance were obtained through
molecular dynamics simulations. Our findings demonstrate that BCR-ABL1 compound
mutants confer different levels of TKI resistance, necessitating rational
treatment selection to optimize clinical outcome.
PMID- 25132502
TI - Genetic targeting of microglia.
AB - Genetic targeting of microglia and other myeloid cells in the central nervous
system (CNS) is highly desirable as they are critical effectors and regulators of
changes in CNS homeostasis during development as well as in health and disease.
Therefore, genetic reprogramming of microglia could constitute a central approach
for potentially reducing disease burden. Previous attempts to target only
microglia in vivo failed because of the similarities to their hematopoietic
relatives in the circulation. However, this concept has been challenged by recent
results of developmental and gene expression profiling studies which used novel
molecular biological tools to unravel the origin of microglia and to define their
role as specialized tissue macrophages clearly distinct from monocytes or
monocyte-derived macrophages. The aim of this review is to recapitulate the
history of microglia targeting approaches and finally highlight recent
achievements in the field. We will discuss the pros and cons of the newly
available genetic tools, their potential for future microglia research and
genetic strategies.
PMID- 25132500
TI - Impaired hypercarbic and hypoxic responses from developmental loss of cerebellar
Purkinje neurons: implications for sudden infant death syndrome.
AB - Impaired responsivity to hypercapnia or hypoxia is commonly considered a
mechanism of failure in sudden infant death syndrome (SIDS). The search for
deficient brain structures mediating flawed chemosensitivity typically focuses on
medullary regions; however, a network that includes Purkinje cells of the
cerebellar cortex and its associated cerebellar nuclei also helps mediate
responses to carbon dioxide (CO2) and oxygen (O2) challenges and assists
integration of cardiovascular and respiratory interactions. Although cerebellar
nuclei contributions to chemoreceptor challenges in adult models are well
described, Purkinje cell roles in developing models are unclear. We used a model
of developmental cerebellar Purkinje cell loss to determine if such loss
influenced compensatory ventilatory responses to hypercapnic and hypoxic
challenges. Twenty-four Lurcher mutant mice and wild-type controls were
sequentially exposed to 2% increases in CO2 (0-8%) or 2% reductions in O2 (21
13%) over 4 min, with return to room air (21% O2/79% N2/0% CO2) between each
exposure. Whole body plethysmography was used to continuously monitor tidal
volume (TV) and breath frequency (f). Increased f to hypercapnia was
significantly lower in mutants, slower to initiate, and markedly lower in
compensatory periods, except for very high (8%) CO2 levels. The magnitude of TV
changes to increasing CO2 appeared smaller in mutants but only approached
significance. Smaller but significant differences emerged in response to hypoxia,
with mutants showing smaller TV when initially exposed to reduced O2 and lower f
following exposure to 17% O2. Since cerebellar neuropathology appears in SIDS
victims, developmental cerebellar neuropathology may contribute to SIDS
vulnerability.
PMID- 25132501
TI - Markers of angiogenesis associated with surgical attenuation of congenital
portosystemic shunts in dogs.
AB - BACKGROUND: Dogs with congenital portosystemic shunts (CPSS) have hypoplasia of
the intrahepatic portal veins. Surgical CPSS attenuation results in the
development of the intrahepatic portal vasculature, the precise mechanism for
which is unknown, although new vessel formation by angiogenesis is suspected.
HYPOTHESIS: That the degree of portal vascular development and the increase in
portal vascularization after CPSS attenuation is significantly associated with
hepatic vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2)
gene expression and serum VEGF concentration. ANIMALS: Client-owned dogs with
CPSS undergoing surgical treatment. Forty-nine dogs were included in the gene
expression data and 35 in the serum VEGF data. MATERIALS AND METHODS: Dogs
surgically treated by partial or complete CPSS attenuation were prospectively
recruited. Relative gene expression of VEGF and VEGFR2 was measured in liver
biopsy samples taken at initial and follow-up surgery using quantitative
polymerase chain reaction. Serum VEGF concentration was measured before and after
CPSS attenuation using a canine specific ELISA. Statistical significance was set
at the 5% level (P <= .05). RESULTS: There was a significant increase in the mRNA
expression of VEGFR2 after partial attenuation (P = .006). Dogs that could
tolerate complete attenuation had significantly greater VEGFR2 mRNA expression
than those that only tolerated partial attenuation (P = .037). Serum VEGF
concentration was significantly increased at 24 (P < .001) and 48 (P = .003)
hours after attenuation. CONCLUSIONS AND CLINICAL IMPORTANCE: These findings
suggest that intrahepatic angiogenesis is likely to occur after the surgical
attenuation of CPSS in dogs, and contributes to the development of the
intrahepatic vasculature postoperatively.
PMID- 25132503
TI - Reduced beta-cell reserve and pancreatic volume in survivors of childhood acute
lymphoblastic leukaemia treated with bone marrow transplantation and total body
irradiation.
AB - BACKGROUND: Impaired glucose tolerance (IGT) and diabetes mellitus (DM) occur
more frequently after bone marrow transplantation and total body irradiation
(BMT/TBI), but the mechanism is unclear. This study investigates insulin
sensitivity, beta-cell reserve and pancreatic volume in adult survivors of
childhood acute lymphoblastic leukaemia (ALL). METHOD: Survivors (aged 16-26
years) of ALL treated with BMT/TBI (10-14.4 Gy) Group 1 (n = 20, 10 m) were
compared with a chemotherapy-only Group 2 (n = 28, 11 m). Participants underwent
assessments of insulin sensitivity by whole body composite-insulin-sensitivity
index (ISIcomp ) from oral glucose tolerance tests (OGTTs); first (AIRarg , AIRg
, AUCin10 ) and second (AUC in second phase ) phase insulin responses from
arginine-intravenous glucose tolerance tests; and pancreatic volume by abdominal
magnetic resonance imaging (MRI). Data were analysed by odds ratio, Chi-square or
Fisher's exact tests, Student's t-tests, analysis of covariance (ancova) and
Pearson's or partial correlations (5% significance). RESULTS: Abnormal OGTTs were
documented in Group 1 (DM = 2, IGT = 7). Insulin secretion adjusted for insulin
sensitivity was lower in Group 1 than Group 2 as a whole [LogAIRarg (P = 0.008),
logAIRg (P = 0.013) and logAUCin10 (P = 0.014)] and after exclusion of those with
abnormal glucose tolerance [logAIRarg (P = 0.011), logAIRg (P = 0.007) and
logAUCin10 (P = 0.006)]. Group 1 had lower pancreatic volume than Group 2 [52.0
(14.2) vs 72.8 (23.5), P = 0.001] cm(3) , and results were consistent after
adjustment for size by body surface area (P = 0.019). Pancreatic volume
correlated with logAIRarg adjusted log ISIcomp (partial correlation = 0.34, P =
0.025). CONCLUSIONS: Adult survivors of childhood BMT/TBI for ALL demonstrated
reduced beta-cell reserve and smaller pancreatic volume, both likely additional
aetiological factors, with reduced insulin sensitivity, in their increased risk
of diabetes.
PMID- 25132504
TI - Gas in the retropharyngeal space: descending necrotising mediastinitis.
PMID- 25132505
TI - Israel-Gaza conflict.
PMID- 25132506
TI - Chikungunya virus control: is a vaccine on the horizon?
PMID- 25132508
TI - Utilizing intraspecific variation in phenotypic plasticity to bolster
agricultural and forest productivity under climate change.
AB - Climate change threatens the ability of agriculture and forestry to meet growing
global demands for food, fibre and wood products. Information gathered from
genotype-by-environment interactions (G * E), which demonstrate intraspecific
variation in phenotypic plasticity (the ability of a genotype to alter its
phenotype in response to environmental change), may prove important for
bolstering agricultural and forest productivity under climate change.
Nonetheless, very few studies have explicitly quantified genotype plasticity
productivity relationships in agriculture or forestry. Here, we conceptualize the
importance of intraspecific variation in agricultural and forest species
plasticity, and discuss the physiological and genetic factors contributing to
intraspecific variation in phenotypic plasticity. Our discussion highlights the
need for an integrated understanding of the mechanisms of G * E, more extensive
assessments of genotypic responses to climate change under field conditions, and
explicit testing of genotype plasticity-productivity relationships. Ultimately,
further investigation of intraspecific variation in phenotypic plasticity in
agriculture and forestry may prove important for identifying genotypes capable of
increasing or sustaining productivity under more extreme climatic conditions.
PMID- 25132507
TI - Safety and tolerability of chikungunya virus-like particle vaccine in healthy
adults: a phase 1 dose-escalation trial.
AB - BACKGROUND: Chikungunya virus--a mosquito-borne alphavirus--is endemic in Africa
and south and southeast Asia and has recently emerged in the Caribbean. No drugs
or vaccines are available for treatment or prevention. We aimed to assess the
safety, tolerability, and immunogenicity of a new candidate vaccine. METHODS: VRC
311 was a phase 1, dose-escalation, open-label clinical trial of a virus-like
particle (VLP) chikungunya virus vaccine, VRC-CHKVLP059-00-VP, in healthy adults
aged 18-50 years who were enrolled at the National Institutes of Health Clinical
Center (Bethesda, MD, USA). Participants were assigned to sequential dose level
groups to receive vaccinations at 10 MUg, 20 MUg, or 40 MUg on weeks 0, 4, and
20, with follow-up for 44 weeks after enrolment. The primary endpoints were
safety and tolerability of the vaccine. Secondary endpoints were chikungunya
virus-specific immune responses assessed by ELISA and neutralising antibody
assays. This trial is registered with ClinicalTrials.gov, NCT01489358. FINDINGS:
25 participants were enrolled from Dec 12, 2011, to March 22, 2012, into the
three dosage groups: 10 MUg (n=5), 20 MUg (n=10), and 40 MUg (n=10). The protocol
was completed by all five participants at the 10 MUg dose, all ten participants
at the 20 MUg dose, and eight of ten participants at the 40 MUg dose; non
completions were for personal circumstances unrelated to adverse events. 73
vaccinations were administered. All injections were well tolerated, with no
serious adverse events reported. Neutralising antibodies were detected in all
dose groups after the second vaccination (geometric mean titres of the half
maximum inhibitory concentration: 2688 in the 10 MUg group, 1775 in the 20 MUg
group, and 7246 in the 40 MUg group), and a significant boost occurred after the
third vaccination in all dose groups (10 MUg group p=0.0197, 20 MUg group
p<0.0001, and 40 MUg group p<0.0001). 4 weeks after the third vaccination, the
geometric mean titres of the half maximum inhibitory concentration were 8745 for
the 10 MUg group, 4525 for the 20 MUg group, and 5390 for the 40 MUg group.
INTERPRETATION: The chikungunya VLP vaccine was immunogenic, safe, and well
tolerated. This study represents an important step in vaccine development to
combat this rapidly emerging pathogen. Further studies should be done in a larger
number of participants and in more diverse populations. FUNDING: Intramural
Research Program of the Vaccine Research Center, National Institute of Allergy
and Infectious Diseases, and National Institutes of Health.
PMID- 25132509
TI - Production of D-lactic acid in a continuous membrane integrated fermentation
reactor by genetically modified Saccharomyces cerevisiae: enhancement in D-lactic
acid carbon yield.
AB - Poly d-lactic acid is an important polymer because it improves the
thermostability of poly l-lactic acid by stereo complex formation. To demonstrate
potency of continuous fermentation using a membrane-integrated fermentation
reactor (MFR) system, continuous fermentation using genetically modified
Saccharomyces cerevisiae which produces d-lactic acid was performed at the low pH
and microaerobic conditions. d-Lactic acid continuous fermentation using the MFR
system by genetically modified yeast increased production rate by 11-fold
compared with batch fermentation. In addition, the carbon yield of d-lactic acid
in continuous fermentation was improved to 74.6 +/- 2.3% compared to 39.0 +/-
1.7% with batch fermentation. This dramatic improvement in carbon yield could not
be explained by a reduction in carbon consumption to form cells compared to batch
fermentation. Further detailed analysis at batch fermentation revealed that the
carbon yield increased to 76.8% at late stationary phase. S. cerevisiae, which
exhibits the Crabtree-positive effect, demonstrated significant changes in
metabolic activities at low sugar concentrations (Rossignol et al., Yeast, 20,
1369-1385, 2003). Moreover, lactate-producing S. cerevisiae requires ATP supplied
not only from the glycolytic pathway but also from the TCA cycle (van Maris et
al., Appl. Environ. Microbiol., 70, 2898-2905, 2004). Our finding was revealed
that continuous fermentation, which can maintain the conditions of both a low
sugar concentration and air supply, results in Crabtree-positive and lactate
producing S. cerevisiae for suitable conditions of d-lactic acid production with
respect to redox balance and ATP generation because of releasing the yeast from
the Crabtree effect.
PMID- 25132510
TI - [Premature constriction of the ductus arteriosus].
PMID- 25132511
TI - [Therapeutic approach to paediatric septic arthritis: are we too aggressive?].
PMID- 25132513
TI - 17beta-Estradiol administration promotes delayed cutaneous wound healing in 40
week ovariectomised female mice.
AB - This study investigated the effect of 17beta-estradiol on wound healing in 40
week ovariectomised female mice. Thirty-six-week-old female mice were divided
into three groups: medication with 17beta-estradiol after ovariectomy (OVX +
17beta-estradiol), ovariectomy (OVX) and sham (SHAM). The mice received two full
thickness wounds, and the OVX + 17beta-estradiol group was administered 17beta
estradiol at 0.01 g/day until healing. In the OVX + 17beta-estradiol group, the
ratio of wound area was significantly smaller than those of the OVX and SHAM
groups on days 1-3, 5, 6, 8-12 and 9-12, respectively, the numbers of neutrophils
and macrophages were significantly smaller than those on days 3 and 7, the ratio
of re-epithelialisation was significantly higher than those on days 3 and 11, the
ratio of myofibroblasts was significantly higher than those on day 11 and smaller
on day 14, and the ratio of collagen fibres was significantly larger than that of
the OVX group on days 7-14. We found that 17beta-estradiol administration
promotes cutaneous wound healing in 40-week female mice by reducing wound area,
shortening inflammatory response, and promoting re-epithelialisation, collagen
deposition and wound contraction. Our results suggest that cutaneous wound
healing that is delayed because of ageing is promoted by exogenous and continuous
17beta-estradiol administration.
PMID- 25132514
TI - Oxidative damage in diabetics: insights from a graduate study in La Reunion
University.
AB - Due to the growing incidence of diabetes in developed nations, there is a
compelling case to be made for teaching graduate students more deeply about
mechanisms underlying this disease. Diabetes is associated with enhanced
oxidative stress and protein glycation via the covalent binding of glucose
molecules. Albumin represents the major plasmatic protein and undergoes enhanced
glycoxidative modifications in diabetic condition. La Reunion Island, a French
department located in the Indian Ocean exhibit a growing incidence of diabetes.
At the University of La Reunion, our research group named GEICO (Groupe d'Etude
sur l'Inflammation Chronique et l'Obesite) participated to foster research and
training in diabetes context and focuses on the impact of glycated albumin
mediated oxidative stress on cell physiopathology. A laboratory course was
designed by our group to introduce graduate students to cutting edge techniques
in redox biology while providing insights into scientific processes and methods.
This two weeks research laboratory training took place at CYROI, a local
biotechnology center that provides advanced facilities for research, business,
and education. Using histochemistry, molecular biology, biochemical techniques,
student investigated oxidative damages in liver from leptin receptor deficient
diabetic mice compared to control littermates. In addition, they used an in vitro
model by assaying oxidative impact of glycated albumin on hepatoma carcinoma
HepG2 cells. This article gives an overview of the organization and protocol used
by the students during their two weeks training in the laboratory. Therefore, it
may be helpful for teaching graduate students techniques used in research
laboratory working on redox biology.
PMID- 25132512
TI - Lactate dehydrogenase and caspase activity in nasopharyngeal secretions are
predictors of bronchiolitis severity.
AB - BACKGROUND: Bronchiolitis is the leading cause of hospitalization in infants.
Biomarkers of disease severity might help in clinical management. OBJECTIVE: To
determine the clinical predictiveness of NW-LDH, NW-caspase 3/7, and NW-LDH/NW
caspase 3/7 ratio in bronchiolitis. METHODS: Previously healthy children less
than 24 months of age with bronchiolitis were recruited from the Texas Children's
emergency room and intensive care unit from October 2010 to April 2011.
Demographic, clinical information, and NW samples were obtained at enrollment. NW
samples were analyzed for respiratory viruses, caspase 3/7, and LDH. RESULTS: A
viral pathogen was detected in 91.6% of 131 children, with the most common being
respiratory syncytial virus and human rhinovirus. A single infection was found in
61.8% of subjects and co-infection in 29.8%. Children admitted to ICU had
significantly higher NW-LDH than children sent home from the ER or admitted to
the general floor (P = 0.02). Children infected with RSV had the highest NW-LDH
concentration (P = 0.03) compared with other viral infections. NW-LDH and NW
caspase were significantly correlated (r = 0.77, P < 0.0001). The univariate
models showed NW-LDH and NW-LDH/NW- caspase 3/7 ratio were directly associated
with hospitalization. Mutivariate regression analyses suggested a complex
interaction between the biomarkers, demographics, and disposition. CONCLUSIONS:
NW-LDH, NW-caspase 3/7 and NW-LDH/NW-caspase 3/7 ratio and their interactions
with demographic factors are predictive of bronchiolitis severity and can help
distinguish children requiring ICU-level care from those admitted to the general
floor, or discharged home from the emergency center.
PMID- 25132515
TI - Magnetic ring anastomosis of suprahepatic vena cava: novel technique for liver
transplantation in rat.
AB - To improve the technique of suprahepatic vena cava (SHVC) reconstruction in rat
OLT, novel magnetic rings were designed and manufactured to facilitate
reconstruction of SHVC and shorten the anhepatic time. One-hundred and twenty
adult male Wistar rats were randomly divided into two groups: rings group (n =
30), using magnetic rings for SHVC reconstruction; suture group (n = 30), 7/0
prolene suture was used for SHVC running anastomosis as control. Cuff techniques
were used for portal vein and infrahepatic vena cava reconstruction as Kamada and
Calne described. The bile duct was reconnected with a stent. The hepatic re
arterialization was omitted. In the rings group, the SHVC reconstruction took
0.91 +/- 0.24 (mean +/- SD) min; the anhepatic phase and the recipient operation
time were 5.63 +/- 0.65 min and 36.02 +/- 8.02 min, respectively. In suture
group, the anastomotic time of SHVC was 10.40 +/- 2.11 min; the anhepatic phase
and the recipient operation time were 17.76 +/- 2.51 and 49.38 +/- 12.06 min,
respectively, and there was statistically significant difference between the two
groups. The ALT levels reached peak at 24 h post-OLT (186.2 +/- 32.5 IU/l) and
restored to normal level at 96 h gradually. In the rings group, 29 of 30 rats
survived at day 7 and 28 of 30 rats survived at day 30. In contrast, only 25 of
30 recipients in suture group remained alive at day 7 and 22 of 30 remained alive
at day 30 (P < 0.05). Better anastomotic healing was founded in rings group by
pathology and scanning electron microscope. The magnetic rings technique provides
a novel, simple method for SHVC reconstruction of OLT in rat. It significantly
shortens anhepatic phase, while the success rate of the operation is
satisfactory.
PMID- 25132516
TI - A randomised controlled trial of PEGASUS, a psychoeducational programme for young
people with high-functioning autism spectrum disorder.
AB - BACKGROUND: Psychoeducation is an essential component of postdiagnostic care for
people with ASD (autism spectrum disorder), but there is currently no evidence
base for clinical practice. We designed, manualised and evaluated PEGASUS
(psychoeducation group for autism spectrum understanding and support), a group
psychoeducational programme aiming to enhance the self-awareness of young people
with ASD by teaching them about their diagnosis. METHODS: This single-blind RCT
(randomised control trial) involved 48 young people (9-14 years) with high
functioning ASD. Half were randomly assigned to PEGASUS, administered in six
weekly group sessions, with the others receiving no additional intervention. ASD
related self-awareness, the primary outcome, was evaluated using the bespoke
Autism Knowledge Quiz (AKQ). Secondary outcome measures included the Rosenberg
Self-Esteem Scale. All measures were collected during home visits and scored by
researchers blind to group assignment. The trial is registered on ClinicalTrials
(NCT01187940, http://www.clinicaltrials.gov) and was funded by the Baily Thomas
Charitable Trust. RESULTS: Bootstrap multiple regression showed ASD knowledge
(beta = .29, p < .001, 95% CIs [0.13, 0.44]) and ASD self-awareness (beta = .42,
p = .001, 95% CIs [0.17, 0.67]), measured by number of ASD-related personal
strengths and difficulties listed by participants, increased for those who
attended PEGASUS (n = 24) compared with controls (n = 24). There was no effect of
PEGASUS on self-esteem by self-report (beta = .10, p = .404, 95% CIs [-0.14,
0.35]) or parent report (beta = .12, p = .324, 95% CIs [-0.12, 0.36]).
CONCLUSIONS: After PEGASUS, participants had more general knowledge about ASD,
and showed a greater awareness of their collection of unique strengths and
difficulties associated with ASD. Psychoeducation did not lower self-esteem. This
RCT provides initial evidence for PEGASUS's efficacy as a psychoeducation
programme for people with ASD.
PMID- 25132517
TI - Advances in classification, basic mechanisms and clinical science in ankylosing
spondylitis and axial spondyloarthritis.
AB - The field of spondyloarthritis (SpA) has seen huge advances over the past 5
years. The classification of axial disease has been redefined by the axial SpA
criteria that incorporate disease captured before radiographic damage is evident
as well as established erosive sacroiliac joint disease. Our knowledge of
genetics and basic immunological pathways has progressed significantly. In
addition, revolutionary progress has been achieved with the availability of
tumour necrosis factor inhibitors for treating patients with moderate to severe
disease. In parallel, several of novel biomarkers have been identified that show
significant promise for the future. Advances in magnetic resonance imaging have
helped define positive disease. We have identified that T1 and short tau
inversion recovery sequences are best for the diagnosis of axial SpA, and
gadolinium contrast is not additive for diagnosis. Progress has been made in
identifying potential agents and strategies that reduce radiographic progression.
Several referral strategies aimed at appropriate identification of patients have
been trialled and found to be effective. There is still substantial work ahead,
but the advances of the last 5 years have made a huge and tangible difference at
the clinical coalface, and we suggest that this trend will continue.
PMID- 25132518
TI - Altered manifestations of skin disease at sites affected by neurological deficit.
AB - BACKGROUND: The contribution of the nervous system to inflammation in general and
inflammatory skin disease in particular has been underappreciated. It is now
apparent that an intact neural component is required for the conventional
clinical manifestations of many inflammatory skin diseases. OBJECTIVES: To
investigate the relationship between nerve damage and skin disease. METHODS:
Previous individual reports since 1966 were collected systematically and the
clinical observations described therein were placed within current concepts of
neurogenic inflammation. RESULTS: We reviewed the literature and identified 23
cases of alterations in the appearance or distribution of skin disorders in
patients with acquired central or peripheral neural damage or dysfunction. In 19
cases, near or complete resolution of pre-existing skin lesions occurred in areas
directly or indirectly supplied by a subsequently injured nervous system.
Exacerbation or new onset of skin lesions occurred in only four cases. The neural
deficits described included damage within the peripheral or central nervous
system resulting in pure sensory, pure motor or combined sensory and motor
deficits. CONCLUSIONS: These cases highlight the importance of neural innervation
and neurogenic inflammation in the development of inflammatory skin disease and
prompt further examination of the use of neural blockade as an adjunctive therapy
in the treatment of inflammatory dermatoses.
PMID- 25132519
TI - Efficacy and tolerability of treatment with azacitidine for 5 days in elderly
patients with acute myeloid leukemia.
AB - Acute myeloid leukemia (AML) patients aged >= 60 years tolerate standard
induction chemotherapy poorly. Therapy with azacitidine at a dose of 75
mg/m(2)/day for 7 days appears to be better tolerated, and is approved by the
Food and Drug Administration (FDA) for the treatment of elderly AML patients with
bone marrow (BM) blast counts of 20-30%. Here, we report the results of a
prospective, phase 2, open-label study that evaluated the tolerability and
efficacy of a 5-day regimen of single-agent subcutaneous azacitidine 100
mg/m(2)/day administered every 28 days in 15 elderly patients with newly
diagnosed AML, 14 of whom had BM blast counts >30%. The overall response rate was
47%. Complete remission, partial remission, and hematologic improvement were
achieved by 20, 13, and 13% of patients, respectively. Median overall survival
was 355 days for the entire cohort, and 532 days for responders. Median time to
best response was 95 days, and median treatment duration was 198 days (range = 13
724 days). Grade 3-4 hematologic toxicities comprised predominantly febrile
neutropenia (40%) and thrombocytopenia (20%). Febrile neutropenia was the most
common cause of hospitalization. Nonhematologic toxicities, consisting of
injection-site skin reactions and fatigue (Grades 1-2), occurred in 73% (n = 11)
of patients. No treatment-related deaths occurred during the study. The dose and
schedule of therapy remained constant in all but four patients. The findings of
this study suggest that administration of subcutaneous azacitidine 100
mg/m(2)/day for 5 days every 28 days is a feasible, well-tolerated, and effective
alternative to standard induction chemotherapy in elderly patients with AML.
PMID- 25132520
TI - A pilot validation of multi-echo based echo-planar correlated spectroscopic
imaging in human calf muscles.
AB - A current limitation of MR spectroscopic imaging of multiple skeletal muscles is
prolonged scan duration. A significant reduction in the total scan duration using
the echo-planar correlated spectroscopic imaging (EP-COSI) sequence was
accomplished using two bipolar readout trains with different phase-encoded echoes
for one of two spatial dimensions within a single repetition time (TR). The
second bipolar readout was used for spatially encoding the outer k-space, whereas
the first readout was used for the central k-space only. The performance of this
novel sequence, called multi-echo based echo-planar correlated spectroscopic
imaging (ME-EPCOSI), was demonstrated by localizing specific key features in calf
muscles and bone marrow of 11 healthy volunteers and five subjects with type 2
diabetes (T2D). A 3 T MRI-MRS scanner equipped with a transmit-receive extremity
coil was used. Localization of the ME-EPCOSI sequence was in good agreement with
the earlier single-readout based EP-COSI sequence and the required scan time was
reduced by a factor of two. In agreement with an earlier report using single
voxel based 2D MRS, significantly increased unsaturated pools of intramyocellular
lipid (IMCL) and extramyocellular lipid (EMCL) and decreased IMCL and EMCL
unsaturation indices (UIs) were observed in the soleus and tibialis anterior
muscle regions of subjects with T2D compared with healthy controls. In addition,
significantly decreased choline content was observed in the soleus of T2D
subjects compared with healthy controls. Multi-voxel characterization of IMCL and
EMCL ratios and UI in the calf muscle may be useful for the non-invasive
assessment of altered lipid metabolism in the pathophysiology of T2D.
PMID- 25132521
TI - Prevalence of postpartum infections: a population-based observational study.
AB - We investigated the prevalence of postpartum infections among women giving birth
during 1 year in a population-based observational/questionnaire study at seven
hospitals in the southeast region of Sweden. Of the women >99% (n = 11,124)
received a questionnaire to inquire if they had endometritis, mastitis, or wound,
urinary tract or any other infection within 2 months postpartum and whether they
received antibiotics for this. Prevalence rates for infections and antibiotic
treatment were estimated. The response rate was 60.1%. At least one infectious
episode was reported by 10.3% of the women and 7.5% had received antibiotics. The
prevalence for infections with and without antibiotics were, respectively,
mastitis 4.7% and 2.9%, urinary tract infection 3.0% and 2.4%, endometritis 2.0%
and 1.7%, wound infection 1.8% and 1.2%. There was no inter-county difference in
infection prevalence. Clinical postpartum infections in a high-resource setting
are relatively common.
PMID- 25132523
TI - Bias induced transition from an ohmic to a non-ohmic interface in supramolecular
tunneling junctions with Ga2O3/EGaIn top electrodes.
AB - This study describes that the current rectification ratio, R = |J|(-2.0
V)/|J|(+2.0 V) for supramolecular tunneling junctions with a top-electrode of
eutectic gallium indium (EGaIn) that contains a conductive thin (0.7 nm)
supporting outer oxide layer (Ga2O3), increases by up to four orders of magnitude
under an applied bias of >+1.0 V up to +2.5 V; these junctions did not change
their electrical characteristics when biased in the voltage range of +/-1.0 V.
The increase in R is caused by the presence of water and ions in the
supramolecular assemblies which react with the Ga2O3/EGaIn layer and increase the
thickness of the Ga2O3 layer. This increase in the oxide thickness from 0.7 nm to
~2.0 nm changed the nature of the monolayer-top-electrode contact from an ohmic
to a non-ohmic contact. These results unambiguously expose the experimental
conditions that allow for a safe bias window of +/-1.0 V (the range of biases
studies of charge transport using this technique are normally conducted) to
investigate molecular effects in molecular electronic junctions with Ga2O3/EGaIn
top-electrodes where electrochemical reactions are not significant. Our findings
also show that the interpretation of data in studies involving applied biases of
>1.0 V may be complicated by electrochemical side reactions which can be
recognized by changes of the electrical characteristics as a function voltage
cycling or in current retention experiments.
PMID- 25132522
TI - Ranolazine attenuates mechanical allodynia associated with demyelination injury.
AB - OBJECTIVE: The aim of this study was to determine whether ranolazine, a new
medication that targets sodium channels to improve cardiac ischemia and angina,
could be an effective analgesic agent for pain associated with demyelination
injury. BACKGROUND: Many agents have been used to treat neuropathic pain but not
all neuropathic conditions respond similarly to treatment. We have demonstrated
that ranolazine, an agent that blocks voltage-gated sodium channels Nav 1.4, 1.5,
1.7, and 1.8, is effective in attenuating mechanical hyperalgesia in both
complete Freund's adjuvant and spared nerve injury preclinical models of
inflammatory and neuropathic pain, respectively. Here we test the efficacy of
this drug in a newly validated model of demyelination injury that responds
uniquely to a number of treatment options. METHODS: After determination of
baseline nerve conduction velocities (NCVs) and withdrawal responses from heat
and mechanical stimulation in male Sprague-Dawley rats (300-350 g), 1 MUg/30 MUL
of doxorubicin was injected into one sciatic nerve. The contralateral nerve
provided a sham-injected control. Two weeks after doxorubicin injection, NCV and
sensitivity to heat and mechanical stimulation were reassessed before and after
treatment with ranolazine (10, 30, 50 mg/kg) administered intraperitoneally using
an experimenter-blinded, randomized design. RESULTS: Doxorubicin injection
produced a significant hyperalgesic effect in response to mechanical but not heat
stimulation. Conduction velocities in the injected limbs were reduced when
compared with controls. Ranolazine reduced mechanical allodynia with peak
efficacy at 30 mg/kg. Fifty milligram/kilogram ranolazine restored NCVs by
approximately 50%, but had no effect in the uninjected limb. CONCLUSIONS:
Ranolazine exerts broad-spectrum actions to reduce mechanical allodynia that is
associated with peripheral demyelination injury.
PMID- 25132524
TI - Determinants of Gli2 co-activation of wildtype and naturally truncated androgen
receptors.
AB - BACKGROUND: Gli2, a transcription factor in the Hedgehog pathway, is
overexpressed in castrate-resistant prostate cancer (PCa). Previously we showed
that Gli2 overexpression increased transcriptional activity of androgen receptor
(AR) and conferred androgen growth-independence to normally growth-dependent PCa
cells. Here we localized the regions of AR-Gli2 protein interaction and
determined the domains within Gli2 needed for AR co-activation. METHODS: Co
immunoprecipitation and GST-pulldown assays were used to define AR-Gli binding
domains. Co-activation assays using androgen-responsive promoter reporters were
used to define Gli2 regions needed for AR co-activation. Chromatin
immunoprecipitation (ChIP) assays were used to confirm nuclear interactions of
Gli2 with AR in PCa cells. RESULTS: The Gli2 C-terminal domain (CTD) is
sufficient for AR co-activation. Two elements within the CTD were required: (1)
an AR binding domain within aa628-897; and (2) at least part of the Gli2
transactivation domain within aa1252-1586. In turn, Gli2 binds the tau5/AF5
ligand-independent activation domain in the AR N-terminus. Mutations in the WxxLF
motif in tau5/AF5 greatly diminished binding to Gli2-CTD. Gli2 interaction with
AR tau5/AF5 was further substantiated by the ability of Gli2/Gli2-CTD to co
activate truncated AR splice variants (AR-V7/ARV567es). ChIP assays confirmed
that Gli2 associates with chromatin at androgen response elements found near
androgen-responsive genes in LNCaP cells. These assays also showed that AR
associates with chromatin containing a Gli-response element near a Gli-responsive
gene. CONCLUSION: Our findings indicate that Gli2 overexpression in PCa cells
might support development of castration resistant PCa through AR co-activation
and suggests that AR might modulate transcription from Gli2.
PMID- 25132527
TI - Host-derived CD8+ dendritic cells protect against acute graft-versus-host disease
after experimental allogeneic bone marrow transplantation.
AB - Graft-versus-host disease (GVHD) is a frequent life-threatening complication
after allogeneic hematopoietic stem cell transplantation (HSCT) and induced by
donor-derived T cells that become activated by host antigen-presenting cells. To
address the relevance of host dendritic cell (DC) populations in this disease, we
used mouse strains deficient in CD11c(+) or CD8alpha(+) DC populations in a model
of acute GVHD where bone marrow and T cells from BALB/c donors were transplanted
into C57BL/6 hosts. Surprisingly, a strong increase in GVHD-related mortality was
observed in the absence of CD11c(+) cells. Likewise, Batf3-deficient (Batf3(-/-))
mice that lack CD8alpha(+) DCs also displayed a strongly increased GVHD-related
mortality. In the absence of CD8alpha(+) DCs, we detected an increased activation
of the remaining DC populations after HSCT, leading to an enhanced priming of
allogeneic T cells. Importantly, this was associated with reduced numbers of
regulatory T cells and transforming growth factor-beta levels, indicating an
aggravated failure of peripheral tolerance mechanisms after HSCT in the absence
of CD8alpha(+) DCs. In summary, our results indicate a critical role of
CD8alpha(+) DCs as important inducers of regulatory T cell-mediated tolerance to
control DC activation and T cell priming in the initiation phase of GVHD.
PMID- 25132528
TI - Crime event 3D reconstruction based on incomplete or fragmentary evidence
material--case report.
AB - Using our own experience in 3D analysis, the authors will demonstrate the
possibilities of 3D crime scene and event reconstruction in cases where
originally collected material evidence is largely insufficient. The necessity to
repeat forensic evaluation is often down to the emergence of new facts in the
course of case proceedings. Even in cases when a crime scene and its surroundings
have undergone partial or complete transformation, with regard to elements
significant to the course of the case, or when the scene was not satisfactorily
secured, it is still possible to reconstruct it in a 3D environment based on the
originally-collected, even incomplete, material evidence. In particular cases
when no image of the crime scene is available, its partial or even full
reconstruction is still potentially feasible. Credibility of evidence for such
reconstruction can still satisfy the evidence requirements in court.
Reconstruction of the missing elements of the crime scene is still possible with
the use of information obtained from current publicly available databases. In the
study, we demonstrate that these can include Google Maps((r)*), Google Street
View((r)*) and available construction and architecture archives.
PMID- 25132529
TI - Preterm birth and neonatal mortality in China in 2011.
AB - OBJECTIVE: To determine the incidence of preterm birth, its regional
distribution, and associated neonatal mortality in mainland China. METHODS: In a
multicenter, hospital-based investigation of preterm birth, 2011 data were
obtained from the seven administrative regions of mainland China. Between one and
three subcenters were randomly selected for each administrative region, followed
by secondary and tertiary hospitals within the chosen subcenters. Data were
obtained from women's medical records, and obstetric and perinatal events were
summarized. RESULTS: Data for 107,905 deliveries were analyzed, which included
7769 (7.1%) preterm births (occurring between 28 and 37 weeks of pregnancy). The
incidence varied among regions. Late preterm birth (between 34 and 37 weeks)
accounted for 5495 (70.7%) of preterm births. The neonatal mortality rate was 33
deaths per 1000 live preterm births. Of the 254 neonatal deaths, 147 (57.9%)
occurred after very preterm birth (between 28 and 32 weeks). Overall, 4519
(58.2%) preterm births occurred by cesarean. CONCLUSION: The distribution of
preterm birth across China is unbalanced, and neonatal mortality associated with
preterm birth is high.
PMID- 25132530
TI - Unilateral microphthalmia or anophthalmia in eight pythons (Pythonidae).
AB - OBJECTIVE: To provide morphological descriptions of microphthalmia or
anophthalmia in eight pythons using microcomputerized tomography (MUCT), magnetic
resonance imaging (MRI), and histopathology. ANIMALS STUDIED: Seven Burmese
pythons (Python bivittatus) and one ball python (P. regius) with clinically
normal right eyes and an abnormal or missing left eye. PROCEDURE: At the time of
euthanasia, four of the eight snakes underwent necropsy. Hereafter, the heads of
two Burmese pythons and one ball python were examined using MUCT, and another
Burmese python was subjected to MRI. Following these procedures, the heads of
these four pythons along with the heads of an additional three Burmese pythons
were prepared for histology. RESULTS: All eight snakes had left ocular openings
seen as dermal invaginations between 0.2 and 2.0 mm in diameter. They also had
varying degrees of malformations of the orbital bones and a limited presence of
nervous, glandular, and muscle tissue in the posterior orbit. Two individuals had
small but identifiable eyes. Furthermore, remnants of the pigmented embryonic
framework of the hyaloid vessels were found in the anophthalmic snakes.
Necropsies revealed no other macroscopic anomalies. CONCLUSIONS: Eight pythons
with unilateral left-sided microphthalmia or anophthalmia had one normal eye and
a left orbit with malformed or incompletely developed ocular structures along
with remnants of fetal structures. These cases lend further information to a
condition that is often seen in snakes, but infrequently described.
PMID- 25132531
TI - The influence of hydrogen bonding on the nonlinear optical properties of a
semiorganic material NH4B[D-(+)-C4H4O5]2.H2O: a theoretical perspective.
AB - In this work, a potential semiorganic nonlinear optical candidate NH4B[D-(+)
(C4H4O5)]2.H2O (NBC) has been studied using Density Functional Theory. The origin
of the second harmonic generation (SHG) effect of NBC crystals for the NH4B[D-(+)
(C4H4O5)]2.H2O molecular complex is explained by employing a combination of the
density of states, SHG density and molecular orbital analysis. It reveals a way
in which the organic and ammonium groups affect the SHG processes in a
significantly different manner in the crystals and the molecular complex. In
particular, the role of hydrogen bonding interaction in influencing the
electronic structure and nonlinear optical properties is explicitly identified
and explained.
PMID- 25132526
TI - Detecting local residue environment similarity for recognizing near-native
structure models.
AB - We developed a new representation of local amino acid environments in protein
structures called the Side-chain Depth Environment (SDE). An SDE defines a local
structural environment of a residue considering the coordinates and the depth of
amino acids that locate in the vicinity of the side-chain centroid of the
residue. SDEs are general enough that similar SDEs are found in protein
structures with globally different folds. Using SDEs, we developed a procedure
called PRESCO (Protein Residue Environment SCOre) for selecting native or near
native models from a pool of computational models. The procedure searches similar
residue environments observed in a query model against a set of representative
native protein structures to quantify how native-like SDEs in the model are. When
benchmarked on commonly used computational model datasets, our PRESCO compared
favorably with the other existing scoring functions in selecting native and near
native models.
PMID- 25132532
TI - Antifreezes act as catalysts for methane hydrate formation from ice.
AB - Contrary to the thermodynamic inhibiting effect of methanol on methane hydrate
formation from aqueous phases, hydrate forms quickly at high yield by exposing
frozen water-methanol mixtures with methanol concentrations ranging from 0.6-10
wt% to methane gas at pressures from 125 bars at 253 K. Formation rates are some
two orders of magnitude greater than those obtained for samples without methanol
and conversion of ice is essentially complete. Ammonia has a similar catalytic
effect when used in concentrations of 0.3-2.7 wt%. The structure I methane
hydrate formed in this manner was characterized by powder X-ray diffraction and
Raman spectroscopy. Steps in the possible mechanism of action of methanol were
studied with molecular dynamics simulations of the Ih (0001) basal plane exposed
to methanol and methane gas. Simulations show that methanol from a surface
aqueous layer slowly migrates into the ice lattice. Methane gas is preferentially
adsorbed into the aqueous methanol surface layer. Possible consequences of the
catalytic methane hydrate formation on hydrate plug formation in gas pipelines,
on large scale energy-efficient gas hydrate formation, and in planetary science
are discussed.
PMID- 25132525
TI - Neonatal handling: an overview of the positive and negative effects.
AB - As one of the first rodent models designed to investigate the effects of early
life experiences, the neonatal handling paradigm has helped us better understand
how subtle changes in the infant environment can powerfully drive
neurodevelopment of the immature brain in typical or atypical trajectories. Here,
we review data from more than 50 years demonstrating the compelling effects of
neonatal handling on behavior, physiology, and neural function across the
lifespan. Moreover, we present data that challenge the classical view of neonatal
handling as an animal model that results only in positive/beneficial outcomes.
Indeed, the overall goal of this review is to offer the suggestion that the
effects of early-life experiences-including neonatal handling-are nuanced rather
than unidirectional. Both beneficial and negative outcomes may occur, depending
on the parameters of testing, sex of the subject, and neurobehavioral system
analyzed.
PMID- 25132533
TI - Fine needle cytology of intrathyroid epidermoid cyst.
PMID- 25132534
TI - Evaluation of microbial communities and symbionts in Ixodes ricinus and ungulate
hosts (Cervus elaphus and Ovis aries) from shared habitats on the west coast of
Norway.
AB - Recent reports suggest a potential for transmission of a newly discovered
rickettsial endosymbiont, Midichloria mitochondrii, to animals and humans from
feeding ticks (Ixodes ricinus). Using molecular methods; I. ricinus, sheep and
red deer in Anaplasma phagocytophilum-endemic areas of Norway, were examined to
see if they were infected by M. mitochondrii or related organisms like Wolbachia
pipientis and Rickettsia spp. A total of 532 ticks collected from pastures, 76
blood samples from grazing lambs and 12 organ samples from hunted deer, were
analyzed during the study. All larval pools, 60.4% pooled nymphs and 35.1% of
adult ticks were positive for M. mitochondrii. There was a significant difference
between geographical areas in the prevalence of M. mitochondrii infection among
nymphs. A total of 2.2% pooled nymphs and 5.3% adult ticks were positive for A.
phagocytophilum. Eleven percent of pooled nymphs were positive for Borrelia spp,
2.2% of pooled nymphs and 3.5% of adult ticks were positive for Rickettsia spp.
and none of the ticks were positive for W. pipientis. The prevalence of A.
phagocytophilum infection was 54% and 75% in grazing lambs and deer,
respectively. No animals were positive for Borrelia spp., M. mitochondrii,
Rickettsia spp. or W. pipientis. The reported findings suggest that M.
mitochondrii is widespread in tick populations at different geographical sites,
and may appear in co-infection with A. phagocytophilum, Borrelia spp. and
Rickettsia spp. in ticks.
PMID- 25132535
TI - Detection of an undescribed Rickettsia sp. in Ixodes boliviensis from Costa Rica.
AB - Ixodes boliviensis is a tick of carnivores that is common on domestic dogs. The
only Rickettsia that has been detected previously in this species is 'Candidatus
Rickettsia andeanae'. We report the detection of an undescribed Rickettsia sp.,
named strain IbR/CRC, in I. boliviensis collected from dogs in Costa Rica.
Analyses of gltA, ompA, and htrA partial sequences place Rickettsia sp. strain
IbR/CRC in the group of R. monacensis, also close to an endosymbiont of Ixodes
scapularis and other undescribed rickettsiae. It was not possible to isolate
Rickettsia sp. strain IbR/CRC in Vero E6 or C6/36 cell lines. Isolation and
further characterization of Rickettsia sp. strain IbR/CRC and the other
undescribed rickettsiae are required to determine their taxonomic status and
pathogenic potential.
PMID- 25132536
TI - Use of plastic tips in artificial feeding of Dermacentor (Anocentor) nitens
females Neumann, 1897 (Acari: Ixodidae).
AB - The establishment of laboratory colonies of ticks is often hampered by their lack
of adaptation to alternative hosts. The aim of this study was to artificially
feed partially engorged Dermacentor (Anocentor) nitens females through plastic
tips, and to identify what are the optimal conditions of application of this
technique to get as much as possible close to the natural conditions. The
technique of artificial feeding through plastic tips allowed the engorgement of
D. nitens ticks to a final weight within the normal range for the species.
PMID- 25132537
TI - High-dose alcohol intoxication differentially modulates cognitive subprocesses
involved in response inhibition.
AB - Aside from well-known physiological effects, high-dose alcohol intoxication
(a.k.a. binge drinking) can lead to aversive social and legal consequences
because response inhibition is usually compromised under the influence of
alcohol. Although the behavioral aspects of this phenomenon were reported on
extensively, the underlying neurophysiological mechanisms mediating this
disinhibition are unclear. To close this gap, we used both behavioral and
neurophysiological measures (event-related potentials, ERPs) to investigate which
subprocesses of response inhibition are altered under the influence of high-dose
alcohol intoxication. Using a within-subject design, we asked young healthy
participants (n = 27) to complete a GO/NOGO task once sober and once intoxicated
(approximately 1.20/00). During intoxication, high-dose alcohol effects were
highest in a condition where the participants could not rely on automated
stimulus-response mapping processes during response inhibition. In this context,
the NOGO-P3 (ERP), that likely depends on dopaminergic signaling within
mesocorticolimbic pathways and is thought to reflect motor inhibition and/or the
evaluation of inhibitory processes, was altered in the intoxicated state. In
contrast to this, the N2 component, which largely depends on nigrostriatal
dopamine pathways and is thought to reflect inhibition on a pre-motor level, was
not altered. Based on these results, we demonstrate that alcohol-induced changes
of dopaminergic neurotransmission do not exert a global effect on response
inhibition. Instead, changes are highly subprocess-specific and seem to mainly
target mesocorticolimbic pathways that contribute to motor inhibition and the
evaluation of such.
PMID- 25132538
TI - Sequential infusion of donor-derived dendritic cells with donor lymphocyte
infusion for relapsed hematologic cancers after allogeneic hematopoietic stem
cell transplantation.
AB - Donor lymphocyte infusion (DLI) is often given to induce a graft-versus-leukemia
(GVL) effect after allogeneic hematopoietic stem cell transplantation (HSCT).
However, efficacy of DLI is limited in most hematologic cancers. As antigen
presenting cells, dendritic cells (DC) bolster immune responses. We conducted a
Phase I trial testing the coinfusion of DC followed by DLI. DC were generated by
culturing peripheral blood mononuclear cells from HLA matched-related donors in
GM-CSF and IL-4 for 7 days, followed by TNF-alpha for 3 days. DC were
administered intravenously on 3 dose levels (5 * 10(6) ; 1 * 10(7) ; 5 * 10(7)
cells). DLI (3 * 10(7) CD3+ cells/kg) was administered intravenously 1 day after
the DC. Sixteen patients with hematologic cancers relapsed after HSCT were
treated. A maximum tolerated dose for DC was not reached. Two of 16 patients met
criteria for DLT within 10 weeks of the infusion: 1 idiopathic respiratory
failure, 1 ventricular cardiac arrest. None developed grade III/IV GVHD. One
patient developed grade II acute intestinal graft-vs.-host disease (GVHD) and 1
chronic GVHD within 6 months of the infusion. Both resolved with corticosteroids.
Four of 14 patients evaluable for disease response achieved durable remissions
and are alive and cancer free 6.7, 8.4, 8.8, and 10.1 years from infusion.
Sequential infusion of donor-derived DC with DLI is feasible in patients with
relapsed hematologic cancers after allogeneic HSCT. Future studies may consider
donor DC preloaded with tumor antigens to investigate whether DC infusion could
augment the GVL effect.
PMID- 25132539
TI - Safety and efficacy of balloon-occluded transcatheter arterial chemoembolization
using miriplatin for hepatocellular carcinoma.
AB - AIM: Balloon-occluded transcatheter arterial chemoembolization (B-TACE) using a
microballoon catheter was performed to administrate miriplatin, and the early
therapeutic efficacy and safety of the procedure were evaluated. METHODS: Out of
158 patients who received miriplatin using B-TACE for hepatocellular carcinoma,
49 patients with a single lesion at either stage I or II (according to the Liver
Cancer Study Group of Japan) were evaluated in comparison with 48 matched
patients who received miriplatin using conventional TACE (C-TACE). RESULTS: The
mean total dose and median dose of miriplatin in each group were 32.5 +/- 31.7 mg
and 20 mg (C-TACE) and 50.1 +/- 31.3 mg and 40 mg (B-TACE), respectively (P <
0.01). The treatment effect (TE) on the target nodule classified as TE4, TE3, TE2
or TE1 was 39.6%, 33.3%, 25.0% and 2.1%, respectively, in the C-TACE group, and
55.1%, 38.8%, 4.1% and 2.0%, respectively, in the B-TACE group. Therefore, the TE
was significantly higher in the B-TACE group (P < 0.05). Although abdominal blood
tests revealed adverse, increased levels of serum alanine aminotransferase (ALT)
in a significantly higher number of B-TACE-treated patients, serum ALT levels
returned to baseline levels in all patients within 1 month. There were no
significant differences in clinical symptoms between the two groups. CONCLUSION:
Compared with C-TACE, B-TACE significantly improved cancer nodule control, and it
was satisfactory in terms of safety. B-TACE is an effective procedure that
enhances the effects of catheterization with miriplatin.
PMID- 25132540
TI - Influence of fluoride in poly(d,l-lactide)/apatite composites on bone formation.
AB - The influence of fluoride in poly(d,l-lactide)/apatite composites on ectopic bone
formation was evaluated in sheep. Nano-apatite powders with different replacement
levels of OH groups by fluoride (F) (0% (F0), 50% (F50), 100% (F100), and
excessive (F200)) were co-extruded with poly (d,l-lactide) at a weight ratio of
1:1. Fluoride release from the composites (CF0, CF50, CF100, and CF200) was
evaluated in vitro and bone formation was assessed after intramuscular
implantation in sheep. After 24 weeks in simulated physiological solution, CF0
and CF50 showed negligible fluoride release, whereas it was considerable from the
CF100 and CF200 composites. Histology showed that the incidence of de novo bone
formation decreased in implants with increasing fluoride content indicating a
negative influence of fluoride on ectopic bone formation. Furthermore, a
significant decrease in resorption of the high fluoride-content composites and a
reduction in the number of multinucleated giant cells were seen. These results
show that instead of promoting, the presence of fluoride in poly(d,l
lactide)/apatite composites seemed to suppresses their resorption and
osteoinductive potential in non-osseous sites.
PMID- 25132541
TI - Interparental violence and childhood adjustment: how and why maternal sensitivity
is a protective factor.
AB - This study examined sensitive parenting as a protective factor in relations
between interparental violence (IPV) and children's coping and psychological
adjustment. Using a multimethod approach, a high-risk sample of 201 two-year-olds
and their mothers participated in three annual waves of data collection.
Moderator analyses revealed that sensitive parenting buffered the risk posed by
IPV on children's changes in externalizing and prosocial development over a 2
year period. Tests of mediated moderation further indicated that sensitive
parenting protected children from the vulnerability of growing up in a violent
home through its association with lower levels of children's angry reactivity to
interparental conflict. Results highlight the significance of identifying the
mechanisms that mediate protective factors in models of family adversity.
PMID- 25132543
TI - Community perceptions of rape and child sexual abuse: a qualitative study in
rural Tanzania.
AB - BACKGROUND: Rape of women and children is recognized as a health and human rights
issue in Tanzania and internationally. Exploration of the prevailing perceptions
in rural areas is needed in order to expand the understanding of sexual violence
in the diversity of Tanzania's contexts. The aim of this study therefore was to
explore and understand perceptions of rape of women and children at the community
level in a rural district in Tanzania with the added objective of exploring those
perceptions that may contribute to perpetuating and/or hindering the disclosure
of rape incidences. METHODS: A qualitative design was employed using focus group
discussions with male and female community members including religious leaders,
professionals, and other community members. The discussions centered on causes of
rape, survivors of rape, help-seeking and reporting, and gathered suggestions on
measures for improvement. Six focus group discussions (four of single gender and
two of mixed gender) were conducted. The focus group discussions were recorded,
transcribed verbatim, and analyzed using manifest qualitative content analysis.
RESULTS: The participants perceived rape of women and children to be a frequent
and hidden phenomenon. A number of factors were singled out as contributing to
rape, such as erosion of social norms, globalization, poverty, vulnerability of
children, alcohol/drug abuse and poor parental care. Participants perceived the
need for educating the community to raise their knowledge of sexual violence and
its consequences, and their roles as preventive agents. CONCLUSIONS: In this
rural context, social norms reinforce sexual violence against women and children,
and hinder them from seeking help from support services. Addressing the
identified challenges may promote help-seeking behavior and improve care of
survivors of sexual violence, while changes in social and cultural norms are
needed for the prevention of sexual violence.
PMID- 25132542
TI - Description of Kuraishia piskuri f.a., sp. nov., a new methanol assimilating
yeast and transfer of phylogenetically related Candida species to the genera
Kuraishia and Nakazawaea as new combinations.
AB - The new anamorphic yeast Kuraishia piskuri, f.a., sp. nov. is described for three
strains that were isolated from insect frass from trees growing in Florida, USA
(type strain, NRRL YB-2544, CBS 13714). Species placement was based on
phylogenetic analysis of nuclear gene sequences for the D1/D2 domains of large
subunit rRNA, small subunit rRNA, translation elongation factor-1alpha, and
subunits B1 and B2 of RNA polymerase II B. From this analysis, the anamorphic
species Candida borneana, Candida cidri, Candida floccosa, Candida hungarica, and
Candida ogatae were transferred to the genus Kuraishia as new combinations and
Candida anatomiae, Candida ernobii, Candida ishiwadae, Candida laoshanensis,
Candida molendini-olei, Candida peltata, Candida pomicola, Candida populi,
Candida wickerhamii, and Candida wyomingensis were transferred to the genus
Nakazawaea.
PMID- 25132544
TI - Role of sediments in modifying the toxicity of two Roundup formulations to six
species of larval anurans.
AB - The role of sediment in modifying the toxicity of the original formulation of
Roundup(r) and Roundup WeatherMAX(r) was examined in aqueous laboratory tests.
Six species of anurans (Bufo fowleri, Hyla chrysoscelis, Rana catesbeiana, Rana
clamitans, Rana sphenocephala, and Rana pipiens) were exposed at Gosner stage 25
to concentrations of the 2 herbicide formulations in 96-h, static, nonrenewal
experiments in the presence and absence of sediment. All species tested had lower
median lethal concentration values in water-only exposures of both formulations
compared with exposures with sediment. Sediment significantly altered the potency
slopes in all tests with the exceptions of H. chrysoscelis and R. clamitans when
exposed to the original formulation of Roundup and H. chrysoscelis and R.
sphenocephala when exposed to Roundup WeatherMAX. Thresholds were significantly
different in all tests, including those in which potency slopes did not differ.
Based on water-sediment exposures of the original formulation of Roundup, all 6
species tested had a margin of safety when compared with the predicted
environmental concentration of the highest label application rate. Of the 6
species, 5 had a margin of safety when exposed to Roundup WeatherMAX. During
incidental exposures in the field, sediments and organic matter present in
aquatic systems provide significant sources of environmental ligands. If used
according to label instructions, both herbicides should pose minimal risk to
anuran amphibians in actual field applications. Environ Toxicol Chem 2014;33:2616
2620. (c) 2014 SETAC.
PMID- 25132545
TI - Structure and mechanism of Zn2+-transporting P-type ATPases.
AB - Zinc is an essential micronutrient for all living organisms. It is required for
signalling and proper functioning of a range of proteins involved in, for
example, DNA binding and enzymatic catalysis. In prokaryotes and photosynthetic
eukaryotes, Zn(2+)-transporting P-type ATPases of class IB (ZntA) are crucial for
cellular redistribution and detoxification of Zn(2+) and related elements. Here
we present crystal structures representing the phosphoenzyme ground state (E2P)
and a dephosphorylation intermediate (E2.Pi) of ZntA from Shigella sonnei,
determined at 3.2 A and 2.7 A resolution, respectively. The structures reveal a
similar fold to Cu(+)-ATPases, with an amphipathic helix at the membrane
interface. A conserved electronegative funnel connects this region to the
intramembranous high-affinity ion-binding site and may promote specific uptake of
cellular Zn(2+) ions by the transporter. The E2P structure displays a wide
extracellular release pathway reaching the invariant residues at the high
affinity site, including C392, C394 and D714. The pathway closes in the E2.Pi
state, in which D714 interacts with the conserved residue K693, which possibly
stimulates Zn(2+) release as a built-in counter ion, as has been proposed for
H(+)-ATPases. Indeed, transport studies in liposomes provide experimental support
for ZntA activity without counter transport. These findings suggest a mechanistic
link between PIB-type Zn(2+)-ATPases and PIII-type H(+)-ATPases and at the same
time show structural features of the extracellular release pathway that resemble
PII-type ATPases such as the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase
(SERCA) and Na(+), K(+)-ATPase. These findings considerably increase our
understanding of zinc transport in cells and represent new possibilities for
biotechnology and biomedicine.
PMID- 25132546
TI - Hallucigenia's onychophoran-like claws and the case for Tactopoda.
AB - The Palaeozoic form-taxon Lobopodia encompasses a diverse range of soft-bodied
'legged worms' known from exceptional fossil deposits. Although lobopodians
occupy a deep phylogenetic position within Panarthropoda, a shortage of derived
characters obscures their evolutionary relationships with extant phyla
(Onychophora, Tardigrada and Euarthropoda). Here we describe a complex feature in
the terminal claws of the mid-Cambrian lobopodian Hallucigenia sparsa--their
construction from a stack of constituent elements--and demonstrate that
equivalent elements make up the jaws and claws of extant Onychophora. A cladistic
analysis, informed by developmental data on panarthropod head segmentation,
indicates that the stacked sclerite components in these two taxa are homologous
resolving hallucigeniid lobopodians as stem-group onychophorans. The results
indicate a sister-group relationship between Tardigrada and Euarthropoda, adding
palaeontological support to the neurological and musculoskeletal evidence uniting
these disparate clades. These findings elucidate the evolutionary transformations
that gave rise to the panarthropod phyla, and expound the lobopodian-like
morphology of the ancestral panarthropod.
PMID- 25132547
TI - Synaptic dysregulation in a human iPS cell model of mental disorders.
AB - Dysregulated neurodevelopment with altered structural and functional connectivity
is believed to underlie many neuropsychiatric disorders, and 'a disease of
synapses' is the major hypothesis for the biological basis of schizophrenia.
Although this hypothesis has gained indirect support from human post-mortem brain
analyses and genetic studies, little is known about the pathophysiology of
synapses in patient neurons and how susceptibility genes for mental disorders
could lead to synaptic deficits in humans. Genetics of most psychiatric disorders
are extremely complex due to multiple susceptibility variants with low penetrance
and variable phenotypes. Rare, multiply affected, large families in which a
single genetic locus is probably responsible for conferring susceptibility have
proven invaluable for the study of complex disorders. Here we generated induced
pluripotent stem (iPS) cells from four members of a family in which a frameshift
mutation of disrupted in schizophrenia 1 (DISC1) co-segregated with major
psychiatric disorders and we further produced different isogenic iPS cell lines
via gene editing. We showed that mutant DISC1 causes synaptic vesicle release
deficits in iPS-cell-derived forebrain neurons. Mutant DISC1 depletes wild-type
DISC1 protein and, furthermore, dysregulates expression of many genes related to
synapses and psychiatric disorders in human forebrain neurons. Our study reveals
that a psychiatric disorder relevant mutation causes synapse deficits and
transcriptional dysregulation in human neurons and our findings provide new
insight into the molecular and synaptic etiopathology of psychiatric disorders.
PMID- 25132548
TI - Structure of malaria invasion protein RH5 with erythrocyte basigin and blocking
antibodies.
AB - Invasion of host erythrocytes is essential to the life cycle of Plasmodium
parasites and development of the pathology of malaria. The stages of erythrocyte
invasion, including initial contact, apical reorientation, junction formation,
and active invagination, are directed by coordinated release of specialized
apical organelles and their parasite protein contents. Among these proteins, and
central to invasion by all species, are two parasite protein families, the
reticulocyte-binding protein homologue (RH) and erythrocyte-binding like
proteins, which mediate host-parasite interactions. RH5 from Plasmodium
falciparum (PfRH5) is the only member of either family demonstrated to be
necessary for erythrocyte invasion in all tested strains, through its interaction
with the erythrocyte surface protein basigin (also known as CD147 and EMMPRIN).
Antibodies targeting PfRH5 or basigin efficiently block parasite invasion in
vitro, making PfRH5 an excellent vaccine candidate. Here we present crystal
structures of PfRH5 in complex with basigin and two distinct inhibitory
antibodies. PfRH5 adopts a novel fold in which two three-helical bundles come
together in a kite-like architecture, presenting binding sites for basigin and
inhibitory antibodies at one tip. This provides the first structural insight into
erythrocyte binding by the Plasmodium RH protein family and identifies novel
inhibitory epitopes to guide design of a new generation of vaccines against the
blood-stage parasite.
PMID- 25132552
TI - A 400-solar-mass black hole in the galaxy M82.
AB - M82 X-1, the brightest X-ray source in the galaxy M82, has been thought to be an
intermediate-mass black hole (100 to 10,000 solar masses) because of its
extremely high luminosity and variability characteristics, although some models
suggest that its mass may be only about 20 solar masses. The previous mass
estimates were based on scaling relations that use low-frequency characteristic
timescales which have large intrinsic uncertainties. For stellar-mass black
holes, we know that the high-frequency quasi-periodic oscillations (100-450
hertz) in the X-ray emission that occur in a 3:2 frequency ratio are stable and
scale in frequency inversely with black hole mass with a reasonably small
dispersion. The discovery of such stable oscillations thus potentially offers an
alternative and less ambiguous means of mass determination for intermediate-mass
black holes, but has hitherto not been realized. Here we report stable, twin-peak
(3:2 frequency ratio) X-ray quasi-periodic oscillations from M82 X-1 at
frequencies of 3.32 +/- 0.06 hertz and 5.07 +/- 0.06 hertz. Assuming that we can
extrapolate the inverse-mass scaling that holds for stellar-mass black holes, we
estimate the black hole mass of M82 X-1 to be 428 +/- 105 solar masses. In
addition, we can estimate the mass using the relativistic precession model, from
which we get a value of 415 +/- 63 solar masses.
PMID- 25132549
TI - Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic
leukaemia.
AB - T-cell acute lymphoblastic leukaemia (T-ALL) is a haematological malignancy with
a dismal overall prognosis, including a relapse rate of up to 25%, mainly because
of the lack of non-cytotoxic targeted therapy options. Drugs that target the
function of key epigenetic factors have been approved in the context of
haematopoietic disorders, and mutations that affect chromatin modulators in a
variety of leukaemias have recently been identified; however, 'epigenetic' drugs
are not currently used for T-ALL treatment. Recently, we described that the
polycomb repressive complex 2 (PRC2) has a tumour-suppressor role in T-ALL. Here
we delineated the role of the histone 3 lysine 27 (H3K27) demethylases JMJD3 and
UTX in T-ALL. We show that JMJD3 is essential for the initiation and maintenance
of T-ALL, as it controls important oncogenic gene targets by modulating H3K27
methylation. By contrast, we found that UTX functions as a tumour suppressor and
is frequently genetically inactivated in T-ALL. Moreover, we demonstrated that
the small molecule inhibitor GSKJ4 (ref. 5) affects T-ALL growth, by targeting
JMJD3 activity. These findings show that two proteins with a similar enzymatic
function can have opposing roles in the context of the same disease, paving the
way for treating haematopoietic malignancies with a new category of epigenetic
inhibitors.
PMID- 25132550
TI - RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis.
AB - Necroptosis has emerged as an important pathway of programmed cell death in
embryonic development, tissue homeostasis, immunity and inflammation. RIPK1 is
implicated in inflammatory and cell death signalling and its kinase activity is
believed to drive RIPK3-mediated necroptosis. Here we show that kinase
independent scaffolding RIPK1 functions regulate homeostasis and prevent
inflammation in barrier tissues by inhibiting epithelial cell apoptosis and
necroptosis. Intestinal epithelial cell (IEC)-specific RIPK1 knockout caused IEC
apoptosis, villus atrophy, loss of goblet and Paneth cells and premature death in
mice. This pathology developed independently of the microbiota and of MyD88
signalling but was partly rescued by TNFR1 (also known as TNFRSF1A) deficiency.
Epithelial FADD ablation inhibited IEC apoptosis and prevented the premature
death of mice with IEC-specific RIPK1 knockout. However, mice lacking both RIPK1
and FADD in IECs displayed RIPK3-dependent IEC necroptosis, Paneth cell loss and
focal erosive inflammatory lesions in the colon. Moreover, a RIPK1 kinase
inactive knock-in delayed but did not prevent inflammation caused by FADD
deficiency in IECs or keratinocytes, showing that RIPK3-dependent necroptosis of
FADD-deficient epithelial cells only partly requires RIPK1 kinase activity.
Epidermis-specific RIPK1 knockout triggered keratinocyte apoptosis and
necroptosis and caused severe skin inflammation that was prevented by RIPK3 but
not FADD deficiency. These findings revealed that RIPK1 inhibits RIPK3-mediated
necroptosis in keratinocytes in vivo and identified necroptosis as a more potent
trigger of inflammation compared with apoptosis. Therefore, RIPK1 is a master
regulator of epithelial cell survival, homeostasis and inflammation in the
intestine and the skin.
PMID- 25132551
TI - Transcriptional interference by antisense RNA is required for circadian clock
function.
AB - Eukaryotic circadian oscillators consist of negative feedback loops that generate
endogenous rhythmicities. Natural antisense RNAs are found in a wide range of
eukaryotic organisms. Nevertheless, the physiological importance and mode of
action of most antisense RNAs are not clear. frequency (frq) encodes a component
of the Neurospora core circadian negative feedback loop, which was thought to
generate sustained rhythmicity. Transcription of qrf, the long non-coding frq
antisense RNA, is induced by light, and its level oscillates in antiphase to frq
sense RNA. Here we show that qrf transcription is regulated by both light
dependent and light-independent mechanisms. Light-dependent qrf transcription
represses frq expression and regulates clock resetting. Light-independent qrf
expression, on the other hand, is required for circadian rhythmicity. frq
transcription also inhibits qrf expression and drives the antiphasic rhythm of
qrf transcripts. The mutual inhibition of frq and qrf transcription thus forms a
double negative feedback loop that is interlocked with the core feedback loop.
Genetic and mathematical modelling analyses indicate that such an arrangement is
required for robust and sustained circadian rhythmicity. Moreover, our results
suggest that antisense transcription inhibits sense expression by mediating
chromatin modifications and premature termination of transcription. Taken
together, our results establish antisense transcription as an essential feature
in a circadian system and shed light on the importance and mechanism of antisense
action.
PMID- 25132553
TI - Proteomic and metabolomic profiling of Valencia orange fruit after natural frost
exposure.
AB - The aim of this study was to evaluate the response of orange fruit (Citrus
sinensis var. Valencia Late) to freezing stress in planta, both immediately after
the natural event and after a week, in order to understand the biochemical and
molecular basis of the changes that later derive in internal and external damage
symptoms. Using two-dimensional differential gel electrophoresis to analyze
exposed and non-exposed fruit, 27 differential protein spots were detected in
juice sacs and flavedo, among all comparisons made. Also, primary and secondary
metabolites relative contents were analyzed in both tissues by gas chromatography
mass spectrometry and liquid chromatography-mass spectrometry, respectively.
Proteins and compounds involved in regulatory functions, iron metabolism,
oxidative damage and carbohydrate metabolism were the most affected.
Interestingly, three glycolytic enzymes were induced by cold, and there was an
increase in fermentation products (volatiles); all of that suggests that more
energy generation might be required from glycolysis to counter the cold stress.
Moreover, a notable increase in sugar levels was observed after frost, but it was
not at the expense of organic acids utilization. Consequently, these results
suggest a probable redistribution of photoassimilates in the frost-exposed
plants, tending to restore the homeostasis altered by that severe type of stress.
Isosinensetin was the most cold-sensitive secondary metabolite because it could
not be detected at all after the frost, constituting a possible tool to early
diagnose freezing damage.
PMID- 25132555
TI - Expression, pharmacology and functional activity of adenosine A1 receptors in
genetic models of Huntington's disease.
AB - Adenosine A1 receptor (A1R) stimulation exerts beneficial effects in response to
various insults to the brain and, although it was found neuroprotective in a
lesional model of Huntington's disease (HD), the features of this receptor in
genetic models of HD have never been explored. In the present study we
characterized the expression, affinity and functional effects of A1Rs in R6/2
mice (the most widely used transgenic model of HD) and in a cellular model of HD.
Binding studies revealed that the density of A1Rs was significantly reduced in
the cortex and the striatum of R6/2 mice compared to age-matched wild-type (WT),
while receptor affinity was unchanged. The selective A1R agonist
cyclopentyladenosine (CPA, 300nM) was significantly more effective in reducing
synaptic transmission in corticostriatal slices from symptomatic R6/2 than in age
matched WT mice. Such an effect was due to a stronger inhibition of glutamate
release from the pre-synaptic terminal. The different functional activities of
A1Rs in HD mice were associated also to a different intracellular signaling
pathway involved in the synaptic effect of CPA. In fact, while the PKA pathway
was involved in both genotypes, p38 MAPK inhibitor SB203580 partially prevented
synaptic effects of CPA in R6/2, but not in WT, mice; moreover, CPA differently
modulated the phosphorylation status of p38 in the two genotypes. In vitro
studies confirmed a different behavior of A1Rs in HD: CPA (100 nM for 5h)
modulated cell viability in STHdh(Q111/Q111) (mhttHD cells), without affecting
the viability of STHdh(Q7/Q7) (wthtt cells). This effect was prevented by the
application of SB203580. Our results demonstrate that in the presence of the HD
mutation A1Rs undergo profound changes in terms of expression, pharmacology and
functional activity. These changes have to be taken in due account when
considering A1Rs as a potential therapeutic target for this disease.
PMID- 25132556
TI - Effects of diet-induced obesity and voluntary exercise in a tauopathy mouse
model: implications of persistent hyperleptinemia and enhanced astrocytic leptin
receptor expression.
AB - The number of patients with Alzheimer's disease (AD) is increasing worldwide, and
available drugs have shown limited efficacy. Hence, preventive interventions and
treatments for presymptomatic AD are currently considered very important. Obesity
rates have also been increasing dramatically and it is an independent risk factor
of AD. Therefore, for the prevention of AD, it is important to elucidate the
pathomechanism between obesity and AD. We generated high calorie diet (HCD)
induced obese tauopathy model mice (PS19), which showed hyperleptinemia but
limited insulin resistance. HCD enhanced tau pathology and glial activation.
Conversely, voluntary exercise with a running wheel normalized the serum leptin
concentration without reducing body weight, and restored the pathological changes
induced by HCD. Thus, we speculated that persistent hyperleptinemia played an
important role in accelerating pathological changes in PS19 mice. Leptin
primarily regulates food intake and body weight via leptin receptor b (LepRb).
Interestingly, the nuclear staining for p-STAT3, which was activated by LepRb,
was decreased in hippocampal neurons in HCD PS19 mice, indicating leptin
resistance. Meanwhile, astroglial activation and the astrocytic expression of a
short LepR isoform, LepRa, were enhanced in the hippocampus of HCD PS19 mice.
Real-time PCR analysis demonstrated that leptin increased mRNA levels for pro
inflammatory cytokines including IL-1beta and TNF-alpha in primary cultured
astrocytes from wild type and LepRb-deficient mice. These observations suggest
that persistent hyperleptinemia caused by obesity induces astrocytic activation,
astrocytic leptin hypersensitivity with enhanced LepRa expression, and enhanced
inflammation, consequently accelerating tau pathology in PS19 mice.
PMID- 25132558
TI - Self-consistent Green's function method for dilute nitride conduction band
structure.
AB - We present a self-consistent Green's function (SCGF) approach for the Anderson
many-impurity model to calculate the band dispersion and density of states near
the conduction band edge in GaN(x)As(1-x) dilute nitride alloys. Two different
models of the N states have been studied to investigate the band structure of
these materials: (1) the two-band model, which assumes all N states have the same
energy, EN; (2) a model which includes a full distribution of N states obtained
by allowing for direct interaction between N sites. The density of states,
projected onto extended and localised states, calculated by the SCGF two-band
model, are in excellent agreement with those previously obtained in supercell
calculations and reveal a gap in the density of states just above E(N), in
contrast with the results of previous non-self-consistent Green's function
calculations. However, including the full distribution of N states in a SCGF
calculation removes this gap, in agreement with experiment.
PMID- 25132554
TI - Animal models of absence epilepsies: what do they model and do sex and sex
hormones matter?
AB - While epidemiological data suggest a female prevalence in human childhood- and
adolescence-onset typical absence epilepsy syndromes, the sex difference is less
clear in adult-onset syndromes. In addition, although there are more females than
males diagnosed with typical absence epilepsy syndromes, there is a paucity of
studies on sex differences in seizure frequency and semiology in patients
diagnosed with any absence epilepsy syndrome. Moreover, it is unknown if there
are sex differences in the prevalence or expression of atypical absence epilepsy
syndromes. Surprisingly, most studies of animal models of absence epilepsy either
did not investigate sex differences, or failed to find sex-dependent effects.
However, various rodent models for atypical syndromes such as the AY9944 model
(prepubertal females show a higher incidence than prepubertal males), BN model
(also with a higher prevalence in males) and the Gabra1 deletion mouse in the
C57BL/6J strain offer unique possibilities for the investigation of the
mechanisms involved in sex differences. Although the mechanistic bases for the
sex differences in humans or these three models are not yet known, studies of the
effects of sex hormones on seizures have offered some possibilities. The sex
hormones progesterone, estradiol and testosterone exert diametrically opposite
effects in genetic absence epilepsy and pharmacologically-evoked convulsive types
of epilepsy models. In addition, acute pharmacological effects of progesterone on
absence seizures during proestrus are opposite to those seen during pregnancy.
17beta-Estradiol has anti-absence seizure effects, but it is only active in
atypical absence models. It is speculated that the pro-absence action of
progesterone, and perhaps also the delayed pro-absence action of testosterone,
are mediated through the neurosteroid allopregnanolone and its structural and
functional homolog, androstanediol. These two steroids increase extrasynaptic
thalamic tonic GABAergic inhibition by selectively targeting neurosteroid
selective subunits of GABAA receptors (GABAARs). Neurosteroids also modulate the
expression of GABAAR containing the gamma2, alpha4, and delta subunits. It is
hypothesized that differences in subunit expression during pregnancy and ovarian
cycle contribute to the opposite effects of progesterone in these two hormonal
states.
PMID- 25132559
TI - Lead and trace element levels in placenta, maternal and cord blood: a cross
sectional pilot study.
AB - AIM: To determine lead (Pb) and trace element (Fe, Zn, Cu, Mg) levels in
placenta, maternal and cord blood; further, to assess the interactions between Pb
and trace elements, if any. METHODS: A cluster of 'at term pregnant women' from
rural and urban areas (n = 30 each, total n = 60) as well as their neonates after
delivery were recruited. Maternal blood, heel prick neonatal blood, placenta and
cord blood were collected at the time of parturition. Pb and trace element levels
in blood/serum, placenta were determined on graphite furnace atomic absorption
(AAS) and flame AAS respectively. Due to sample constraints, only Pb levels were
determined in heel prick blood samples of neonates. RESULTS: There were no major
abnormal signs and symptoms, however, 38% had pale conjunctiva and 13% had
pigmented tongue. The blood lead levels (BLL) were significantly (P < 0.05)
higher in urban post-partum women compared to their rural counterparts. Higher
BLL did not correlate with either pregnancy outcome or neonatal anthropometry.
Maternal serum trace element levels were deficient in both rural and urban women.
Significant (P < 0.01) positive correlation between maternal and neonatal BLL as
well as significant (P < 0.05) inverse correlation between cord BLL and placental
Pb levels were observed. Maternal and cord BLL correlated inversely (P < 0.05)
with maternal and cord serum Fe levels, respectively. CONCLUSION: Urban post
partum women and their neonates were at higher risk with elevated BLL. Estimate
of cord blood Pb may not be the true index of neonatal BLL. These observations
must be confirmed in a larger cohort because prenatal/neonatal screening avoids
the risks associated with rest of life.
PMID- 25132557
TI - Combinatorial targeting of early pathways profoundly inhibits neurodegeneration
in a mouse model of glaucoma.
AB - The endothelin system is implicated in various human and animal glaucomas.
Targeting the endothelin system has great promise as a treatment for human
glaucoma, but the cell types involved and the exact mechanisms of action are not
clearly elucidated. Here, we report a detailed characterization of the endothelin
system in specific cell types of the optic nerve head (ONH) during glaucoma in
DBA/2J mice. First, we show that key components of the endothelin system are
expressed in multiple cell types. We discover that endothelin 2 (EDN2) is
expressed in astrocytes as well as microglia/monocytes in the ONH. The endothelin
receptor type A (Ednra) is expressed in vascular endothelial cells, while the
endothelin receptor type B (Ednrb) receptor is expressed in ONH astrocytes.
Second, we show that Macitentan treatment protects from glaucoma. Macitentan is a
novel, orally administered, dual endothelin receptor antagonist with greater
affinity, efficacy and safety than previous antagonists. Finally, we test the
combinatorial effect of targeting both the endothelin and complement systems as a
treatment for glaucoma. Similar to endothelin, the complement system is
implicated in a variety of human and animal glaucomas, and has great promise as a
treatment target. We discovered that combined targeting of the endothelin
(Bosentan) and complement (C1qa mutation) systems is profoundly protective.
Remarkably, 80% of DBA/2J eyes subjected to this combined inhibition developed no
detectable glaucoma. This opens an exciting new avenue for neuroprotection in
glaucoma.
PMID- 25132560
TI - Antagonistic evolution in an aposematic predator-prey signaling system.
AB - Warning signals within species, such as the bright colors of chemically defended
animals, are usually considered mutualistic, monomorphic traits. Such a view is
however increasingly at odds with the growing empirical literature, showing
nontrivial levels of signal variation within prey populations. Key to
understanding this variation, we argue, could be a recognition that toxicity
levels frequently vary within populations because of environmental heterogeneity.
Inequalities in defense may undermine mutualistic monomorphic signaling, causing
evolutionary antagonism between loci that determine appearance of less well
defended and better defended prey forms within species. In this article, we apply
a stochastic model of evolved phenotypic plasticity to the evolution of prey
signals. We show that when toxicity levels vary, then antagonistic interactions
can lead to evolutionary conflict between alleles at different signaling loci,
causing signal evolution, "red queen-like" evolutionary chase, and one or more
forms of signaling equilibria. A key prediction is that variation in the way that
predators use information about toxicity levels in their attack behaviors
profoundly affects the evolutionary characteristics of the prey signaling
systems. Environmental variation is known to cause variation in many qualities
that organisms signal; our approach may therefore have application to other
signaling systems.
PMID- 25132562
TI - Development of a sensitive amplified luminescent proximity homogeneous assay to
monitor the interactions between pTEFb and Tat.
AB - The viral transactivator protein (Tat) plays an essential role in the replication
of human immunodeficiency type 1 virus (HIV-1) by recruiting the host positive
transcription elongation factor (pTEFb) to the RNA polymerase II transcription
machinery to enable an efficient HIV-1 RNA elongation process. Blockade of the
interaction between Tat and pTEFb represents a novel strategy for developing a
new class of antiviral agents. In this study, we developed a homogeneous assay in
AlphaLISA (amplified luminescent proximity homogeneous assay) format using His
tagged pTEFb and biotinylated Tat to monitor the interaction between Tat and
pTEFb. On optimizing the assay conditions, the signal-to-background ratio was
found to be greater than 10-fold. The assay was validated with untagged Tat and
peptides known to compete with Tat for pTEFb binding. The Z' of the assay is
greater than 0.5, indicating that the assay is robust and can be easily adapted
to a high-throughput screening format. Furthermore, the affinity between Tat and
pTEFb was determined to be approximately 20 pM, and only 7% of purified Tat was
found to be active in forming tertiary complex with pTEFb. Development of this
assay should facilitate the discovery of a new class of antiviral agents
providing HIV-1 patients with broader treatment choices.
PMID- 25132563
TI - Sensitive detection of acetylcholine based on a novel boronate intramolecular
charge transfer fluorescence probe.
AB - A highly sensitive and selective fluorescence method for the detection of
acetylcholine (ACh) based on enzyme-generated hydrogen peroxide (H2O2) and a new
boronate intramolecular charge transfer (ICT) fluorescence probe, 4-(4,4,5,5
tetramethyl-1,3,2-dioxaborolan-2-yl)-N-butyl-1,8-naphthalimide (BN), was
developed. This strategy involves the reaction of ACh with acetylcholinesterase
(AChE) to produce choline, which is further oxidized by choline oxidase (ChOx) to
obtain betaine and H2O2. The enzyme-generated H2O2 reacts with BN and results in
hydrolytic deprotection of BN to generate fluorescent product (4-hydroxyl-N-butyl
1,8-naphthalimide, ON). Two consecutive linear response ranges allow determining
ACh in a wide concentration range with a low detection limit of 2.7 nM
(signal/noise=3). Compared with other fluorescent probes based on the mechanism
of nonspecific oxidation, this reported boronate probe has the advantage of no
interference from other biologically relevant reactive oxygen species (ROS) on
the detection of ACh. This study provides a new method for the detection of ACh
with high selectivity and sensitivity.
PMID- 25132564
TI - Capillary isoelectric focusing of a difficult-to-denature tetrameric enzyme using
alkylurea-urea mixtures.
AB - Capillary isoelectric focusing (cIEF) is normally run under denaturing conditions
using urea to expose any buried protein residues that may contribute to the
overall charge. However, urea does not completely denature some proteins, such as
the tetrameric enzyme Erwinia chrysanthemil-asparaginase (ErA), in which case
electrophoresis-compatible alternative denaturants are required. Here, we show
that alkylureas such as N-ethylurea provide increased denaturation during cIEF.
The cIEF analysis of ErA in 8 M urea alone resulted in a cluster of ill-resolved
peaks with isoelectric points (pI values) in the range 7.4 to 8.5. A combination
of 2.0 to 2.2 M N-ethylurea and 8M urea provided sufficient denaturation of ErA,
resulting in a main peak with a pI of 7.35 and an acidic species minor peak at
7.0, both comparing well with predicted pI values based on the sum of protein
residue pKa values. Recombinant deamidated ErA mutants were also demonstrated to
migrate to pI values consistent with predictions (pI 7.0 for one deamidation).
The quantitation of ErA acidic species in samples from full-scale manufacturing
(1.0-3.5% of total peak area) was found to be reproducible and linear. Use of
alkylureas as denaturing agents in capillary electrophoresis and cIEF should be
considered during biopharmaceutical assay development.
PMID- 25132565
TI - Correction for concentration overestimation of nucleic acids with phenol.
AB - We report a computational method based on ultraviolet (UV) spectra for correcting
the overestimated concentrations of nucleic acid samples contaminated with
TRIzol/phenol. The derived correction formulas were validated using RNA
solutions, double-stranded DNA solutions, and single-stranded oligonucleotide
solutions. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR)
with SYBR Green was performed to assess the level of TRIzol contamination that
can be tolerated for gene expression quantification. After the correction, the
accuracy of the RNA concentrations was greatly improved and there was no
significant difference in the threshold cycle (Ct) values for GAPDH and ACAN
genes in RT-qPCR obtained for RNA contaminated with up to 0.1% TRIzol (phenol
level index [PLI]~5.8-5.9). Similarly, accuracy improvements were also observed
for DNA or oligonucleotides contaminated with phenol using different
concentration correction formulas. In addition, the Ct values and amplification
efficiency of DNA in qPCR were not affected by TRIzol contamination below 1%.
This computational method is easy and convenient to use and reduces the
concentration overestimations greatly.
PMID- 25132561
TI - Connections between TET proteins and aberrant DNA modification in cancer.
AB - DNA methylation has been linked to aberrant silencing of tumor suppressor genes
in cancer, and an imbalance in DNA methylation-demethylation cycles is intimately
implicated in the onset and progression of tumors. Ten-eleven translocation (TET)
proteins are Fe(II)- and 2-oxoglutarate (2OG)-dependent dioxygenases that
successively oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5
formylcytosine (5fC), and 5-carboxylcytosine (5caC), thereby mediating active DNA
demethylation. In this review, we focus on the pathophysiological role of TET
proteins and 5hmC in cancer. We present an overview of loss-of-function mutations
and abnormal expression and regulation of TET proteins in hematological
malignancies and solid tumors, and discuss the potential prognostic value of
assessing TET mutations and 5hmC levels in cancer patients. We also address the
crosstalk between TET and two critical enzymes involved in cell metabolism: O
linked beta-N-acetylglucosamine transferase (OGT) and isocitrate dehydrogenase
(IDH). Lastly, we discuss the therapeutic potential of targeting TET proteins and
aberrant DNA methylation in cancer.
PMID- 25132566
TI - Molecular identification and phylogenetic study of Demodex caprae.
AB - The DNA barcode has been widely used in species identification and phylogenetic
analysis since 2003, but there have been no reports in Demodex. In this study, to
obtain an appropriate DNA barcode for Demodex, molecular identification of
Demodex caprae based on mitochondrial cox1 was conducted. Firstly, individual
adults and eggs of D. caprae were obtained for genomic DNA (gDNA) extraction;
Secondly, mitochondrial cox1 fragment was amplified, cloned, and sequenced;
Thirdly, cox1 fragments of D. caprae were aligned with those of other Demodex
retrieved from GenBank; Finally, the intra- and inter-specific divergences were
computed and the phylogenetic trees were reconstructed to analyze phylogenetic
relationship in Demodex. Results obtained from seven 429-bp fragments of D.
caprae showed that sequence identities were above 99.1% among three adults and
four eggs. The intraspecific divergences in D. caprae, Demodex folliculorum,
Demodex brevis, and Demodex canis were 0.0-0.9, 0.5-0.9, 0.0-0.2, and 0.0-0.5%,
respectively, while the interspecific divergences between D. caprae and D.
folliculorum, D. canis, and D. brevis were 20.3-20.9, 21.8-23.0, and 25.0-25.3,
respectively. The interspecific divergences were 10 times higher than
intraspecific ones, indicating considerable barcoding gap. Furthermore, the
phylogenetic trees showed that four Demodex species gathered separately,
representing independent species; and Demodex folliculorum gathered with canine
Demodex, D. caprae, and D. brevis in sequence. In conclusion, the selected 429-bp
mitochondrial cox1 gene is an appropriate DNA barcode for molecular
classification, identification, and phylogenetic analysis of Demodex. D. caprae
is an independent species and D. folliculorum is closer to D. canis than to D.
caprae or D. brevis.
PMID- 25132567
TI - Silver nanoparticles: a possibility for malarial and filarial vector control
technology.
AB - Green synthesis technology is one of the rapid, reliable and best routes for the
synthesis of silver nanoparticles (AgNPs). There are bioactive compounds with
enormous potential in Azadirachta indica (Neem). The extraordinary mosquitoes
warrant nanotechnology to integrate with novel molecules. This will be
sustainable technology for future. Here, we synthesized AgNPs using aqueous
extracts of leaves and bark of Az. indica (Neem). We tested AgNPs as larvicides,
pupicides and adulticides against the malaria vector Anopheles stephensi and
filariasis vector Culex quinquefasciatus. The results were obtained using UV
visible spectrophotometer and the images were recorded with a transmission
electron microscope (TEM). The efficacy tests were then performed at different
concentrations varying many hours by probit analysis. The synthesized AgNPs were
spherical in shape and with varied sizes (10.47-nm leaf and 19.22-nm bark). The
larvae, pupae and adults of filariasis vector C. quinquefasciatus were found to
be more susceptible to our AgNPs than the malaria vector An. stephensi. The first
and the second instar larvae of C. quinquefasciatus show a mortality rate of 100%
after 30 min of exposure. The results against the pupa of C. quinquefasciatus
were recorded as LC50 4 ppm, LC90 11 ppm and LC99 13 ppm after 3 h of exposure.
In the case of adult mosquitoes, LC50 1.06 MUL/cm(2), LC90 2.13 MUL/cm(2) and
LC99 2.4 MUL/cm(2) were obtained after 4 h of exposure. These results suggest
that our AgNPs are environment-friendly for controlling malarial and filarial
vectors.
PMID- 25132569
TI - Repair of oral mucosal defects with cryopreserved human amniotic membrane grafts:
prospective clinical study.
AB - The aim of this study was to evaluate the clinical outcome of the surgical repair
of oral mucosal defects using cryopreserved human amniotic membrane (HAM) as a
graft material. Thirty-four patients with precancerous lesions such as
leukoplakia, erythroplakia, and verrucous hyperplasia were included. Fresh
amniotic membrane was obtained from women undergoing elective caesarean section;
the membrane was cleaned, prepared in antibiotic solutions, and preserved at -80
degrees C. Results suggested that HAM promotes healing and epithelialization
without specific complications. Thus we conclude that the use of HAM gives
promising results in the repair of post-surgical oral mucosal defects.
PMID- 25132568
TI - The metabolite profiles of the obese population are gender-dependent.
AB - Studies have identified that several amino acids, in particular, branched-chain
amino acids (BCAAs), have increased significantly in obese individuals when
compared to lean individuals. Additionally, these metabolites were strongly
associated with future diabetes, which rendered them prognostic markers suitable
for obese populations. Here we report a metabonomic study that reveals new
findings on the role of these amino acid markers, particularly BCAAs, in a
Chinese cohort including 106 healthy obese and 105 healthy lean participants. We
found that the BCAAs were correlated with insulin resistance and differentially
expressed in obese men, but not in obese women. The results were verified with
two independent groups of participants (Chinese, n = 105 and American, n = 72)
and demonstrate that the serum metabolite profiles of the obese population are
gender-dependent. The study supports the previous findings of a panel of several
key metabolites as prognostic markers of the obese population and highlights the
need to take into account gender differences when using these markers for risk
assessment.
PMID- 25132570
TI - Clinical presentation and treatment outcomes of thyroglossal duct cysts: a
systematic review.
AB - The aim of the present review was to analyze the main clinical signs and symptoms
observed in patients with thyroglossal duct cysts (TGDCs). Secondarily we
investigated the outcomes following the different types of treatment of TGDCs in
children and adults. Three selected strings were run on the PubMed database to
retrieve articles on these topics. A double cross-check was performed on
citations and full-text articles were identified using the study inclusion and
exclusion criteria. A meta-analysis was performed of the data obtained. Overall,
356 articles were identified; 24 (comprising a total of 1371 subjects) satisfied
the inclusion and exclusion criteria. On the basis of the meta-analysis, the
presence of a neck cystic mass was the main clinical presentation of TGDCs, with
a mean rate of 75% (95% confidence interval 72-79%). The mean local wound
infection rate was 4% (95% confidence interval 3-6%), this being the most
frequent complication following treatment. The mean rate of overall recurrence
was 11% (95% confidence interval 9-14%). The Sistrunk procedure appears to be the
better choice for the therapy of TGDCs to avoid recurrences. Further studies on
larger cohorts of patients regarding the minimally invasive treatment options
would be helpful to elucidate and endorse their utilization in selected cases.
PMID- 25132571
TI - Reply to comments on "New protocol to prevent TMJ reankylosis and potentially
life threatening complications in triad patients".
PMID- 25132572
TI - Facial injuries following hyena attack in rural eastern Ethiopia.
AB - Hyenas are effective hunters and will consider humans as potential prey if the
need and opportunity arise. This study describes the circumstances of hyena
attacks, the patterns of injuries sustained, and reconstruction in a resource
poor setting. As part of a charitable surgical mission to Ethiopia in 2012, 45
patients with facial deformities were reviewed, of whom four were victims of
hyena attacks. A semi-structured interview was performed to ascertain the
circumstances of the attack and the subsequent consequences. The age of the
victims at the time of attack varied from 5 to 50 years. The attacks occurred
when the victims were alone and vulnerable and took place in outdoor open spaces,
during the evening or at night. The initial lunge was made to the facial area; if
the jaws closed on the facial bones they were crushed, but in all cases the soft
tissues were grasped and torn from the underlying bone. Reconstruction was
dictated by the extent of soft tissue loss but could normally be obtained by use
of local or regional flaps. Hyenas have been shown to attack humans in a
predictable way and cause injuries that typically involve the soft tissues of the
face.
PMID- 25132573
TI - Multiple mantleomas: an unusual clinical presentation of an intriguing tumour.
PMID- 25132575
TI - Modes of executive function and their coordination: introduction to the special
section.
PMID- 25132574
TI - Stromal microRNA-21 levels predict response to 5-fluorouracil in patients with
pancreatic cancer.
AB - BACKGROUND AND OBJECTIVES: MicroRNA-21 (miR-21) is upregulated and inversely
associated with survival in many cancer types, including pancreatic ductal
adenocarcinoma (PDAC). We studied the predictive value of miR-21 levels for
gemcitabine or 5-fluorouracil (5-FU) response in tumor cells (TCs) or cancer
associated fibroblasts (CAFs) in a cohort of PDAC patients from the RTOG 9704
trial. METHODS: MiR-21 expression in CAFs and TCs, determined by in situ
hybridization, of the 229 PDAC subset from RTOG 9704 was correlated with (i)
histopathology characteristics using a chi-square test; and (ii) patient overall
survival (OS) using the Cox proportional hazards model. RESULTS: MiR-21 was
strongly expressed in TCs and CAFs in 137/182 (75%) and 152/181 (84%) PDACs,
respectively. MiR-21 expression in CAFs for the group given 5-FU for OS: (i)
approached significance in a univariate analysis (hazard ratio [HR], 1.57; 95%
confidence interval [CI], 0.95-2.57; P = 0.07); and (ii) was significant in the
multivariate model (HR, 1.70; 95% CI, 1.03-2.82; P = 0.038). CONCLUSIONS: MiR-21
expression in CAFs was associated with decreased OS in PDAC patients who received
5-FU, but not gemcitabine. These findings begin to identify stromal miR-21 as a
marker to guide chemotherapy choice in PDAC patients.
PMID- 25132576
TI - Associations between salivary alpha-amylase and catecholamines--a multilevel
modeling approach.
AB - Salivary alpha-amylase (sAA) serves as indicator for sympathetic activity.
However, previous findings on the association between aggregated sAA and other
sympathetic markers, namely norepinephrine and epinephrine, were mixed. We
therefore assumed that time-sensitive statistical analyses might help identifying
possible associations of sAA and catecholamines. Data from two studies were
analyzed. In Study 1, 13 men were examined in a randomized repeated within
subjects double-blind study with yohimbine/placebo. In Study 2, 30 men were
randomized in a repeated within-subjects design to psychosocial stress/rest.
Associations of repeatedly assessed sAA, norepinephrine, and epinephrine in blood
were analyzed using multilevel modeling. Over the time course, sAA was
significantly associated with the catecholamines (Study 1: R(2)=.43, Study 2:
R(2)=.09) and both served as mediators of sAA increases. Additional exploratory
analyses suggest stronger associations during challenge/stress than during
placebo/rest. These findings further support sAA as marker of sympathetic
activity.
PMID- 25132577
TI - Virtual reconstruction and geometric morphometrics as tools for paleopathology: a
new approach to study rare developmental disorders of the skeleton.
AB - Survey studies of osteoarchaeological collections occasionally yield specimens
exhibiting rare skeletal developmental disorders. Beyond paleopathological
diagnosis, however, it is often difficult to gain insight into the processes,
mechanisms, and consequences of the pathology, notably because archaeological
specimens are often fragmentary. Here, we propose a combination of virtual
reconstruction (VR) and geometric morphometrics (GM) to address these issues. As
an example, we use VR to reconstruct the only known archaeological specimen
exhibiting persistence of the pelvic triradiate cartilage and compare it via GM
with a set of healthy pelvises representing both sexes and different ontogenetic
stages. Our results evidence (i) a marked deviation of the pathological pelvis
from the adult mean shape, (ii) the retention of typical male features, and (iii)
the retention of a paedomorphic ratio between iliac and ischiopubic size.
Altogether, such data offer new insights into the modularity and integration of
pelvic ontogeny, while at the same time demonstrating the usefulness of a
combined VR/GM approach as complement to classical methods of paleopathology.
PMID- 25132578
TI - Degenerate adaptor sequences for detecting PCR duplicates in reduced
representation sequencing data improve genotype calling accuracy.
AB - RAD-tag is a powerful tool for high-throughput genotyping. It relies on PCR
amplification of the starting material, following enzymatic digestion and
sequencing adaptor ligation. Amplification introduces duplicate reads into the
data, which arise from the same template molecule and are statistically
nonindependent, potentially introducing errors into genotype calling. In shotgun
sequencing, data duplicates are removed by filtering reads starting at the same
position in the alignment. However, restriction enzymes target specific locations
within the genome, causing reads to start in the same place, and making it
difficult to estimate the extent of PCR duplication. Here, we introduce a slight
change to the Illumina sequencing adaptor chemistry, appending a unique four-base
tag to the first index read, which allows duplicate discrimination in aligned
data. This approach was validated on the Illumina MiSeq platform, using double
digest libraries of ants (Wasmannia auropunctata) and yeast (Saccharomyces
cerevisiae) with known genotypes, producing modest though statistically
significant gains in the odds of calling a genotype accurately. More importantly,
removing duplicates also corrected for strong sample-to-sample variability of
genotype calling accuracy seen in the ant samples. For libraries prepared from
low-input degraded museum bird samples (Mixornis gularis), which had low
complexity, having been generated from relatively few starting molecules, adaptor
tags show that virtually all of the genotypes were called with inflated
confidence as a result of PCR duplicates. Quantification of library complexity by
adaptor tagging does not significantly increase the difficulty of the overall
workflow or its cost, but corrects for differences in quality between samples and
permits analysis of low-input material.
PMID- 25132579
TI - Investigation of sporulation in the Desulfotomaculum genus: a genomic comparison
with the genera Bacillus and Clostridium.
AB - The genus Desulfotomaculum, belonging to the Firmicutes, comprises strictly
anaerobic and endospore-forming bacteria capable of dissimilatory sulfate
reduction. These microorganisms are metabolically versatile and are widely
distributed in the environment. Spore formation allows them to survive prolonged
environmental stress. Information on the mechanism of sporulation in
Desulfotomaculum species is scarce. Herein, this process was probed from a
genomic standpoint, using the Bacillus subtilis model system as a reference and
clostridial sporulation for comparison. Desulfotomaculum falls somewhere in
between the Bacillus and Clostridium in terms of conservation of sporulation
proteins. Furthermore, it showcased the conservation of a core regulatory cascade
throughout genera, while uncovering variability in the initiation of sporulation
and the structural characteristics of spores from different genera. In
particular, while in Clostridium species sporulation is not initiated by a
phosphorelay, Desulfotomaculum species harbour homologues of the B. subtilis
proteins involved in this process. Conversely, both Clostridium and
Desulfotomaculum species conserve very few B. subtilis structural proteins,
particularly those found in the outer layers of the spore. Desulfotomaculum
species seem to share greater similarity to the outer layers of Clostridium
difficile.
PMID- 25132580
TI - Pectoralis major myofascial onlay and myocutaneous flaps and pharyngocutaneous
fistula in salvage laryngectomy.
AB - OBJECTIVES/HYPOTHESIS: To review the fistula rate in irradiated patients
undergoing salvage laryngectomy, compare the effect of closure type on fistula
rate, and examine possible perioperative risk factors that might contribute to an
increased fistula rate. STUDY DESIGN: Case series with chart review. METHODS: We
conducted a retrospective review of the University of Pittsburgh head and neck
tumor registry and identified 73 patients from 1998 to 2011 who had received
prior radiation before total laryngectomy or salvage laryngectomy and who had
either primary closure, pectoralis major myofascial (PMMF) flap onlay, or
pectoralis major myocutaneous (PMMC) flap. RESULTS: Fistula was more common in
patients who underwent initial primary closure (45%) than in patients who had
immediate PMMF onlay (10.5%). The fistula rate for patients who underwent
immediate PMMC flap was 28.6%, intermediate to primary closure and PMMF flap.
Several factors were evaluated for relationship to fistula, but no significant
associations were identified. However, patients with fistula tended to have
longer inpatient stays and may have been more likely to have a history of
cardiovascular or hypoxic disease. CONCLUSION: Pharyngocutaneous fistula is a
well-established complication of total laryngectomy and is especially a concern
in patients with a previous history of radiation. Our retrospective review
demonstrates that PMMF onlay flap appears to be more effective in reducing the
rate of fistula compared to primary closure in these patients. Myocutaneous
augmentation flaps, in contrast, have a fairly high fistula rate and may be
better replaced with alternative closures such as free flaps. LEVEL OF EVIDENCE:
4.
PMID- 25132581
TI - Abnormalities in renal tubular phosphate handling in children with sickle cell
disease.
AB - BACKGROUND: The mechanisms responsible for the hyperphosphatemia in patients with
sickle cell disease (SCD) and preserved glomerular filtration rate (GFR) are not
fully understood. The role of fibroblast growth factor 23 (FGF23), a phosphaturic
hormone has not been investigated in SCD. Hence, we evaluated parameters of renal
tubular phosphorus handling and their relation to prevailing FGF23 levels in a
cohort of young SCD patients. METHODS: Renal tubular phosphate handling and
circulating levels of various analytes including FGF23 and parathyroid hormone
(PTH) were measured in 24 children with SCD and normal estimated GFR in a cross
sectional study. Correlation and regression analysis were employed to derive
relationships between serum phosphorus and several variables. RESULTS: Most
children showed elevated age- adjusted serum phosphorus (5.1 +/- 0.7 mg/dl)
levels. Tubular re-absorption of phosphorus(TRP) (96.3 +/- 2.1%) and tubular
maximum re-absorption of phosphorus per unit volume of GFR (TMP/GFR) (4.9 +/- 0.6
mg/dl) were both elevated. Plasma intact FGF23 concentrations were elevated (81
+/- 38 pg/ml) while the average PTH values were normal in most patients (50 +/-
27 pg/ml). Univariate analysis showed significant correlations of serum
phosphorus with TMP/GFR, alkaline phosphatase, age, lactate dehydrogenase (LDH),
and log intact FGF23. TMP/GFR correlated with log intact FGF23 (r = 0.5, P< or =
0.01) but not with PTH. Multiple regression analysis yielded an independent
relationship of serum phosphorus with TMP/GFR. CONCLUSION: The elevated serum
phosphorus concentrations with simultaneously increased TMP/GFR and elevated
FGF23 levels collectively suggest that patients with SCD display proximal tubular
resistance to the action of FGF23 before any decline in GFR.
PMID- 25132583
TI - Incidence and dynamics of active cytomegalovirus infection in allogeneic stem
cell transplant patients according to single nucleotide polymorphisms in donor
and recipient CCR5, MCP-1, IL-10, and TLR9 genes.
AB - Single nucleotide polymorphisms (SNPs) in genes involved in the activation or
regulation of innate and adaptive immune responses may modulate the
susceptibility to and the natural history of certain chronic viral infections.
The current study aimed to investigate whether donor and recipient SNPs in the
chemokine receptor 5 (rs1800023), monocyte chemoattractant protein 1 (rs13900),
interleukin-10 (rs1878672), and Toll-like receptor 9 (rs352140) genes would exert
any influence on the rate of incidence and features of CMV DNAemia in the
allogeneic stem cell transplantation setting. This was a retrospective
observational multicenter study. The cohort consisted of 102 non-consecutive
allogeneic stem cell transplant recipients. SNP genotyping was performed by
allele-specific real-time PCR. CMV surveillance was performed by the pp65
antigenemia assay/and or by real-time PCR. Seventy-three patients developed CMV
DNAemia within the first 100 days after transplantation (71.5%). Neither donor
nor recipient SNPs were associated significantly with the rate of incidence of
active CMV infection, nor with the need for pre-emptive antiviral therapy. Both
the duration of CMV DNAemia and the plasma CMV DNA peak load during episodes were
significantly higher in patients harboring the donor (but not the recipient)
chemokine receptor 5 A/A genotype, than in their A/G and G/G counterparts (P =
0.022 and P = 0.045, respectively). The data reported suggest that SNPs in
chemokine receptor 5 may influence the dynamics of CMV infection in the Allo-SCT
setting.
PMID- 25132585
TI - Gene expression profiling of lung myofibroblasts reveals the anti-fibrotic
effects of cyclosporine.
AB - Cyclosporine, a calcineurin inhibitor, is a potent immunosuppressive agent that
acts chiefly through the inactivation of T-lymphocytes. Several clinical studies
have demonstrated the effectiveness of cyclosporine for treating fibrotic lung
disease, but the underlying mechanism remains elusive. We hypothesized that
cyclosporine exerts direct effects against fibrogenesis of lung myofibroblasts,
and aimed to elucidate the mechanism of this anti-fibrotic effect through gene
expression profiling using DNA microarray analysis. We found that cyclosporine
suppressed the expression of alpha-smooth muscle actin and collagen type I in
myofibroblasts that had been differentiated from a fetal human lung fibroblast
cell line by induction with transforming growth factor (TGF)-beta. Furthermore,
microarray analysis revealed that cyclosporine down-regulated 57 genes whose
expression levels were increased by TGF-beta, and up-regulated 73 genes, whose
expression was decreased by TGF-beta. Classifying these 57 down-regulated and 73
up-regulated genes with the Database for Annotation, Visualization and Integrated
Discovery (DAVID) web tool, we have identified the involvement of several
functional categories, including innate immunity, cytokine interaction, growth
factor, and cancer pathway. Of the identified genes, we selected three fibrosis
related genes, insulin-like growth factor binding protein 2 (IGFBP2), inhibitor
of DNA binding 1 (ID1) and peroxisome proliferator-activated receptor gamma
(PPARG), and validated their expression patterns by quantitative reverse
transcription-polymerase chain reaction. Cyclosporine treatment decreased the
expression levels of IGFBP2 and ID1, but increased PPARG expression. These
results suggest that cyclosporine is a potent anti-fibrotic agent acting on
myofibroblasts. Therefore, cyclosporine shows potential as a novel remedy for
fibrotic lung disease.
PMID- 25132582
TI - Pancreatic stem cells remain unresolved.
AB - Diabetes mellitus is caused by absolute (type 1) or relative (type 2) deficiency
of insulin-secreting islet beta cells. An ideal treatment of diabetes would,
therefore, be to replace the lost or deficient beta cells, by transplantation of
donated islets or differentiated endocrine cells or by regeneration of endogenous
islet cells. Due to their ability of unlimited proliferation and differentiation
into all functional lineages in our body, including beta cells, embryonic stem
cells and induced pluripotent stem cells are ideally placed as cell sources for a
diabetic transplantation therapy. Unfortunately, the inability to generate
functional differentiated islet cells from pluripotent stem cells and the poor
availability of donor islets have severely restricted the broad clinical use of
the replacement therapy. Therefore, endogenous sources that can be directed to
becoming insulin-secreting cells are actively sought after. In particular, any
cell types in the developing or adult pancreas that may act as pancreatic stem
cells (PSC) would provide an alternative renewable source for endogenous
regeneration. In this review, we will summarize the latest progress and knowledge
of such PSC, and discuss ways that facilitate the future development of this
often controversial, but crucial research.
PMID- 25132586
TI - Assessment of the relationship between transepidermal water loss (TEWL) and
severity of clinical signs (CADESI-03) in atopic dogs.
AB - BACKGROUND: Atopic dermatitis (AD) is a common allergic skin disease of dogs.
Objective documentation of disease severity is important for the assessment of
responses to therapeutic interventions. One common means of assessing the
severity of clinical signs is the Canine Atopic Dermatitis Extent and Severity
Index (CADESI)-03. In addition, studies of the biophysical parameters of the skin
suggest that assessment of transepidermal water loss (TEWL) may also have value
for estimation of disease severity. HYPOTHESIS/OBJECTIVES: The aim of the present
study was to verify the correlation between TEWL and CADESI-03 measured at 10
different body sites. ANIMALS: Twenty-six dogs with AD (age range 1-7 years,
median age 3 years). METHODS: The assessment was performed at the following 10
body sites: the lumbar, inguinal, ventral abdominal, interdigital regions,
axillary fossa, lateral thorax, lateral aspect of the antebrachium, concave
surface of the auricle, cheek and bridge of the nose. RESULTS: Positive
correlations were found between TEWL and the total CADESI-03 for the auricle (r =
0.59), bridge of nose (r = 0.62) and interdigital skin (r = 0.47). Positive
correlations were also observed between TEWL and local CADESI-03 scores for the
axillary fossa (r = 0.73), inguinal region (r = 0.55) and interdigital skin (r =
0.77). CONCLUSIONS AND CLINICAL IMPORTANCE: The results indicate that it may be
possible to use measurement of TEWL to assess the severity of skin lesions, but a
positive correlation was found in only five of 10 body regions examined.
PMID- 25132587
TI - Construction of recombinant adenovirus vector containing hBMP2 and hVEGF165 genes
and its expression in rabbit Bone marrow mesenchymal stem cells.
AB - To construct an adenovirus vector co-expressing human bone morphogenetic protein
(hBMP2) and human vascular endothelial growth factor (hVEGF165) as well as green
fluorescence protein (GFP) as a marker, with which the intracellular expression
of the inserted genes could be identified in Bone marrow mesenchymal stem cells
(BM-MSCs). BMP2 and VEGF165 genes were PCR amplified from a cDNA library and
inserted to the polyclonal site of adenovirus shuttle plasmid pAd-MCMV-GFP. The
virus solution (Ad-BMP2-VEGF165) was generated by co-transfecting HEK293 cells
with the constructed recombinant shuttle plasmid pAd-MCMV-BMP2-VEGF165 and
adenovirus helper plasmid pBHGloxDelta (delta) E1, 3Cre. The virus solution was
further purified and virus titer was determined accordingly. The expression of
the target genes was subsequently detected and quantified in rabbit BM-MSCs by
using real time PCR, ELISA and Western blotting. The recombinant adenovirus
vector containing BMP2 and VEGF165 (Ad-BMP2-VEGF165) was successfully
constructed, which was confirmed by Sanger sequencing, colony PCR, as well as
visually detection of GFP, and the titer of the adenovirus was 1*10(10)PFU/mL,
and the proteins level of BMP2 and VEGF165 secreted in the supernatant are
significantly higher than the control. Recombinant adenovirus vector containing
hBMP2 and hVEGF165 genes was successfully constructed. The transfection rate of
BM-MSCs by the adenovirus was high (95% at 100 MOI) and the BMP2 and VEGF165
genes was highly expressed in the cells. The present study provides a method to
efficiently express the target genes in BM-MSCs and an vector for further
research of bone defect repair using dual genes of BMP2 and VEGF165.
PMID- 25132589
TI - [The role of the psychiatrist in the new mental health care].
PMID- 25132588
TI - A randomized trial comparing dual axis rotational versus conventional coronary
angiography in a population with a high prevalence of coronary artery disease.
AB - OBJECTIVES: To compare the safety, radiation dose, and contrast volume between
dual axis rotational coronary angiography (DARCA) and conventional coronary
angiography (CCA). BACKGROUND: CCA is performed in multiple, predefined
stationary views, at different angulations around the patient, for both the left
and right coronary arteries. DARCA (AlluraXperSwingTM, Philips, the Netherlands)
involves a pre-set rotation of the C-arm around the patient and allows for the
visualization of each coronary artery in different views, using a single
automatic pump contrast injection. METHODS: From November 2012 to February 2013,
201 patients were randomly assigned to either CCA (n = 100) or DARCA (n = 101).
Exclusion criteria included acute coronary syndrome (ACS), prior PCI or CABG.
CCAs were performed in 4 acquisition runs for the left coronary artery and 2 to 3
acquisition runs for the right coronary artery, whereas DARCAs were performed in
a single run for each coronary artery. RESULTS: Baseline demographics and
clinical characteristics were similar for both groups. The overall prevalence of
CAD was 77.6%. The DARCA group had a significant reduction in the amount of
contrast, 60 ml (IQR: 52.5-71.5 ml) versus 76 ml (IQR: 68-87 ml), P < 0.0001; and
radiation dose by Air Kerma, 269.5 mGy (IQR: 176-450.5) versus 542.1 mGy (IQR:
370.7-720.8), P < 0.0001. There were fewer patients requiring additional
projections in the DARCA group: 54.0% versus 75.0%; P = 0.002. CONCLUSIONS: In a
population with a high prevalence of CAD, DARCA was safe and resulted in a
significant decrease in contrast volume and radiation dose.
PMID- 25132591
TI - [The working alliance in inpatient treatment for personality disorders and its
connection with patient characteristics: an exploratory study].
AB - BACKGROUND: The working alliance between therapist and patient has been
investigated frequently, but much less is known about the working alliance in
specific patient groups in specific settings. AIM: To obtain insight into the
characteristics of the working alliance in intensive inpatient psychotherapy
involving patients with severe personality disorders, and to pay special
attention to patient characteristics such as diagnosis and attachment. METHOD: At
the end of the first phase of treatment we collected, on the basis of
questionnaires, information about the working alliance and attachment of 60
patients with a severe personality disorders who had received inpatient
psychotherapy. RESULTS: Working alliances with therapist and team were found to
be weaker than in outpatient populations; working alliances with the therapist
proved to be stronger than working alliances with the treatment team. Cluster C
patients developed a better working alliance with the treatment team than did
cluster B patients, particularly in the domain of treatment goals. Patients in
this study turned out to be attached more anxiously and 'avoidantly' than
patients in general outpatient populations; no correlation was found between
patients' attachment and the strength of the working alliance. However, when a
distinction was made between patients with extreme scores and patients with
average scores, results showed that the more anxiously patients felt attached,
the higher were their scores for their working alliance with the treatment team.
CONCLUSION: It is more difficult to establish a working alliance with patients
who have a severe personality disorder than with patients suffering from a less
severe personality disorder. Patients with a severe personality disorder seemed
to show a higher degree of anxious attachment and to have a more critical
attitude to the working alliance.
PMID- 25132592
TI - [Body dysmorphic disorder in cosmetic surgery - prevalence, psychiatric
comorbidity and outcome].
AB - BACKGROUND: Patients suffering from body dysmorphic disorder (bdd) are
preoccupied with a slight or imagined defect in appearance. AIM: First of all, to
review the literature on the prevalence of bdd in cosmetic surgery and thereafter
to review the literature on psychiatric comorbidity and the outcome of surgical
interventions. METHOD: We based our search strategy on Embase, Medline and
PubMed, using the search terms 'body dysmorphic disorder', 'cosmetic surgery',
'prevalence', 'comorbidity' and 'outcome'. Our search covered English and Dutch
literature published after the introduction of bdd in dsm-iii-r and before 1
November, 2013. A study of the relevant articles enabled us to access additional
articles mentioned in these texts. RESULTS: Our initial search strategy turned
out to be too narrow. It was therefore broadened to include 'body dysmorphic
disorder', 'cosmetic surgery', and 'prevalence'. Eventually we included 23
original articles. In 11 of these the prevalence of bdd varied from 3.2 to 53.6%.
Twelve articles on psychiatric comorbidity revealed predominantly mood and
anxiety disorders on axis I and cluster C personality disorders on axis II. Only
two studies reported on the outcome of cosmetic surgery performed on bdd
patients; surgical interventions, however, seemed to result in new preoccupations
with the prolongation of psychiatric comorbidity. CONCLUSION: bdd is a common
psychiatric disorder that can sometimes lead to cosmetic surgery. However, pre
operative screening of bdd patients is vital so that efficient psychiatric
treatment can be initiated and patients are not subjected to surgical
interventions which may be ineffective or even harmful.
PMID- 25132594
TI - [Diagnosis should not be confused with classification in psychiatry].
PMID- 25132593
TI - [Should diagnosis and classification be kept separate in psychiatry?].
AB - BACKGROUND: In medicine it is common practice to diagnose patients before
classifying their symptoms. In psychiatry, however, the two procedures cannot be
kept separate; they overlap and are interlinked. AIM: To discuss relevant
classification systems and the relationship between diagnosis and classification
and to find out what kind of relationship is the best one for psychiatry. METHOD:
The literature was searched and a conceptual analysis was performed on the basis
of relevant literature, manuals and principles formulated by psychiatrists.
RESULTS: It is argued that deliberation, an important part of the diagnostic
process, can only play a significant role if diagnosis and symptom classification
are kept completely separate. In this process of deliberation there should be a
role for clinical phenomena such as improvement of symptoms, worsening of
symptoms, objectification and reification, and psychiatrists should have the
opportunity to consider whether these aspects really belong to the field of
psychiatry. CONCLUSION: In psychiatry the relationship between diagnosis and
symptom classification is not clear-cut. However, since deliberation plays a
major role in psychiatric diagnosis, it is important that psychiatrists continue
to keep diagnosis separate from symptom classification. Unlike other medical
specialists, psychiatrists sometimes classify an illness before making a
diagnosis. Existing guidelines and an all-embracing guideline regarding diagnosis
need to be harmonised. Confusion and misdiagnosis could be reduced if
classifications from two classification systems were to be included in medico
psychiatric diagnosis.
PMID- 25132595
TI - [Good clinical practice and the maintenance of ethical standards in medical
research: advice for junior researchers working in mental health care].
AB - BACKGROUND: In mental health care, more and more research is being done,
particularly in the field of educational programmes. Unfortunately, junior
researchers are often not fully informed about the rules and regulations relating
to research and about medical ethics. Therefore, they are not in a position to
make considered judgements that conform to good clinical practice and acceptable
medical ethics.
AIM: To give practical advice to trainees, stimulating them
to think carefully about ethical standards in patient-related research in mental
health care. METHODS The article provides a practice-based overview of practical
advice and ethical considerations.
RESULTS: We stress that before beginning
their research, researchers should think very carefully about the ethics of
medical research. Instructions and guidelines relating to medical and ethical
standards are to be found in: directive for good clinical practice compiled by
the central committee for human research (CCMO) with the accompanying e-learning
module and in the basic course 'rules and organisation for clinical researchers'
(BROK). Practical tips, illustrated with examples, provide a framework for
stimulating thoughts on medical ethics. Finally, it is important to improve the
ways in which research is embedded in the organisational structure of teaching
programmes.
CONCLUSION: Basic information about GCP and the upholding of
medical and ethical standards in patient-related research can be obtained from
various sources. The main challenge is to ensure that GCP is firmly embedded in
patient-related research undertaken by junior researchers.
PMID- 25132596
TI - [Cryptococcal meningitis and neuropsychiatric consequences of HIV-infection].
AB - A 49-year-old African-born male was admitted to hospital with an acute psychosis.
He had been treated by an internist after being found to have hiv; as a result of
non-compliance over a period of about four months his cd4-count had dropped to
40. Six months earlier he had developed a cryptococcal meningitis, which left him
a number of neurological and psychiatric symptoms. During his stay in hospital
there had to be good collaboration with the specialist in internal medicine whose
dual task was to manage the patient's dramatically low cd4-account as well as his
psychosis. Cryptococcal meningitis is a risk factor for psychiatric disorders and
mortality in hiv-infected persons.
PMID- 25132597
TI - [Reaction on 'Contribution to quality of care or caught in a digital labyrinth?
Experience with electronic records of patients receiving long-term mental health
care' (1)].
PMID- 25132598
TI - [Reaction on 'Minocycline for schizophrenia: a brief overview'].
PMID- 25132599
TI - Suppression of TDO-mediated tryptophan catabolism in glioblastoma cells by a
steroid-responsive FKBP52-dependent pathway.
AB - Tryptophan catabolism is increasingly recognized as a key and druggable molecular
mechanism active in cancer, immune, and glioneural cells and involved in the
modulation of antitumor immunity, autoimmunity and glioneural function. In
addition to the pivotal rate limiting enzyme indoleamine-2,3-dioxygenase,
expression of tryptophan-2,3-dioxygenase (TDO) has recently been described as an
alternative pathway responsible for constitutive tryptophan degradation in
malignant gliomas and other types of cancer. In addition, TDO has been implicated
as a key regulator of neurotoxicity involved in neurodegenerative diseases and
ageing. The pathways regulating TDO expression, however, are largely unknown.
Here, a siRNA-based transcription factor profiling in human glioblastoma cells
revealed that the expression of human TDO is suppressed by endogenous
glucocorticoid signaling. Similarly, treatment of glioblastoma cells with the
synthetic glucocorticoid dexamethasone led to a reduction of TDO expression and
activity in vitro and in vivo. TDO inhibition was dependent on the immunophilin
FKBP52, whose FK1 domain physically interacted with the glucocorticoid receptor
as demonstrated by bimolecular fluorescence complementation and in situ proximity
ligation assays. Accordingly, gene expression profile analyses revealed negative
correlation of FKBP52 and TDO in glial and neural tumors and in normal brain.
Knockdown of FKBP52 and treatment with the FK-binding immunosuppressant FK506
enhanced TDO expression and activity in glioblastoma cells. In summary, we
identify a novel steroid-responsive FKBP52-dependent pathway suppressing the
expression and activity of TDO, a central and rate-limiting enzyme in tryptophan
metabolism, in human gliomas.
PMID- 25132600
TI - The inhibition effects of insulin on BMP2-induced muscle heterotopic
ossification.
AB - Bone morphogenetic proteins (BMPs) play an important role in regulating
osteoblastic differentiation and bone formation. But the diffuse of BMPs into
muscle tissues around bone injury sites often leads to heterotopic ossification,
which has been regarded as one of major side-effects of BMP implementation in
bone defect patients. It raises great demands for exploring effective methods
that preventing BMP-induced heterotopic ossification while not interrupting the
osteoinductive activity of BMPs for in situ bone defect repair. Here we found
insulin, a positive regulator for bone regeneration, inhibited BMP2-induced
muscle heterotopic ossification by suppressing the expression of bone
transcription factor Osterix. By analyzing downstream molecules of insulin
pathway, we found AKT/mTOR/GSK3 signaling was responsible for the inhibition of
insulin on BMP2-induced ossification, and GSK3 inhibitor SB216763 attenuated BMP2
induced muscle heterotopic ossification. The data might shed light on developing
effective clinical therapy for inhibiting muscle heterotopic ossification when
BMPs were used bone defect repair.
PMID- 25132601
TI - Nanovesicles engineered from ES cells for enhanced cell proliferation.
AB - Extracellular vesicles (Exosomes and microvesicles) have drawn wide attentions in
both diagnostic and therapeutic applications, since they are considered to
shuttle biological signals intercellularly. However, further research on exosomes
is limited by their rarity and heterogeneity even after lengthy isolation
processes. In particular, these limitations are challenging in therapeutic
applications. To meet these demands, cell-derived nanovesicles that mimic
exosomes were generated by extruding living embryonic stem cells through micro
filters. These nanovesicles have an enclosed lipid bilayer and contain cellular
contents. The present study investigated the ability of these nanovesicles to
improve proliferation by treating primary murine skin fibroblasts with the
nanovesicles. The treated skin fibroblasts showed higher expression levels of
mRNA, VEGF-alpha, protein levels of TGF-beta collagen I, PCNA, and Ki-67, as well
as enhanced cell proliferation rate and number, compared to non-treated cells.
The results indicate that treatment with the nanovesicles could potentially
contribute to recovery or wound healing process of tissues.
PMID- 25132603
TI - Carbon nanodots featuring efficient FRET for two-photon photodynamic cancer
therapy with a low fs laser power density.
AB - The 5,10,15,20-tetrakis(1-methyl 4-pyridinio) porphyrins (TMPyP), a
photosensitizer used for photodynamic therapy of cancers (PDT), were linked to
carbon dots (CDots) to form the conjugates of CDot-TMPyP by the electrostatic
force. The 415 nm emission band of CDots was well overlapped with the absorption
band of TMPyP, so that the Cdots in conjugates can work as donor to transfer the
energy to TMPyP moiety by fluorescence resonance energy transfer (FRET) with an
FRET efficiency of 45%, determined by the fluorescence lifetime change between
the free CDots and conjugated CDots. The two-photon absorption cross section
(TPACS) of TMPyP is as low as 110 GM and the TMPyP thus be not suitable for two
photon PDT. Whereas the CDots have high TPACS, and their TPACS are excitation
wavelength dependent with the maximum value of 15000 GM at 700 nm. Therefore, the
conjugates of CDot-TMPyP were explored for two-photon excitation (TPE) PDT. The
two-photon image of CDot-TMPyP in Hela cells was clearly seen under the
excitation of a 700 nm femto-second (fs) laser. The singlet oxygen production of
CDot-TMPyP was also much higher than that of TMPyP alone under TPE of a 700 nm fs
laser. The in vitro PDT killing was further achieved with CDot-TMPyP by TPE of
the 700 nm fs laser. Particularly herein the low power density of fs laser from
unfocused laser beam was successfully used to carry out the TPE PDT, because of
the high TPACS of CDots. These results demonstrate that the CDot-TMPyP conjugates
are promising for TPE PDT and needed to investigate further.
PMID- 25132602
TI - Nucleotide biosynthesis arrest by silencing SHMT1 function via vitamin B6-coupled
vector and effects on tumor growth inhibition.
AB - Serine hydroxymethyltransferase isoforms (SHMT1 & SHMT2alpha), which serve as
scaffold protein for the formation of a multi-enzyme complex and generate one
carbon unit for the de novo thymidylate biosynthesis pathway during DNA
synthesis, are vitamin B6 (VB6)-dependent enzyme. Cancer cells with high
proliferation intensity need increased SHMT activation which enforces the
facilitated-diffusion of VB6 for the continuous functioning of thymidylate
synthase cycle. Therefore, SHMT knockdown presents an alternative approach to
prevent DNA synthesis in cancer cells; however, its potential to inhibit cancer
growth remains unknown so far. Here we demonstrated that VB6 coupled to
poly(ester amine) (VBPEA) enforces a high level of VTC (VB6-transporting membrane
carriers)-mediated endocytosis of the complexed SHMT1 siRNA (siSHMT1) to
interrupt the thymidylate biosynthesis pathway of cancer cells. The detrimental
effect of SHMT1 knockdown on the disintegration of multi-enzyme complex resulted
in cell cycle arrest and a decrease in cell's genomic DNA content, leading to
enhanced apoptotic events in cancer cells. A reduction in tumor size was observed
with constant SHMT1 suppression in xenograft mice. This study illustrates how
silencing the SHMT1 expression inhibits cancer growth and the increased VB6
channeling for sustenance of cancer cells promotes VB6-coupled vector to elicit
enhanced delivery of siSHMT1.
PMID- 25132604
TI - A microwell pattern for C17.2 cell aggregate formation with concave cylindrical
surface induced cell peeling.
AB - We have developed a polydimethylsiloxane (PDMS) pattern with arrays of microwells
for the formation of multicellular aggregates by C17.2 neural stem cells. Upon
interfacing with the patterns, the neural stem cells would firstly attach to the
microwell sidewalls, forming cellular strips on day 1 after plating. For channel
connected microwells, cellular strips on the concave semi-cylindrical sidewall
surfaces continued among wells and through channels, followed by strip peeling
due to prestress arising from actin filaments and assembly of suspending cellular
aggregates within the microwells in the following 1-2 days. Our results also
suggested that a small microwell diameter of 80 and 100 MUm and a narrow channel
width of 20 MUm would facilitate the aggregate formation among the structural
dimensions tested. Finite element method (FEM) simulation revealed that cellular
strips on the semi-cylindrical sidewall surfaces peeled under significantly
smaller prestresses (critical peeling prestress, CPP), than cells on flat
substrates. However, the CPP by itself failed to fully account for the difference
in aggregate inducing capability among the patterns addressed, suggesting cell
growth behaviors might play a role. This study thus justified the current
patterning method as a unique and practical approach for establishing 3D neural
stem cell-based assay platforms.
PMID- 25132605
TI - Enhanced angiogenic effect of adipose-derived stromal cell spheroid with low
level light therapy in hind limb ischemia mice.
AB - The aim of this study was to investigate the effects of low-level laser therapy
(LLLT) on transplanted human adipose-derived mesenchymal stem cells (hASCs)
spheroid in a hind limb ischemia animal model. LLLT, hASCs spheroid and hASCs
spheroid transplantation with LLLT (spheroid + LLLT) were applied to the ischemic
hind limbs in athymic mice. The survival, differentiation and secretion of
vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF),
and hepatocyte growth factor (HGF) of the spheroid ASCs were evaluated by
immunohistochemistry and western blots. Spheroid + LLLT group had enhanced the
tissue regeneration, including angiogenesis, compared with the ASC group. The
spheroid ASCs contributed to tissue regeneration via differentiation and
secretion of growth factors. In the spheroid + LLLT group, the survival of
spheroid hASCs increased with a concomitant decrease in apoptosis of spheroid
hASCs in the ischemic hind limb. The secretion of growth factors was stimulated
in the spheroid + LLLT group compared with the ASCs and spheroid group. These
data suggested that LLLT is an effective biostimulator of spheroid hASCs in
tissue regeneration that enhanced the survival of ASCs and stimulated the
secretion of growth factors in the ischemic hind limb.
PMID- 25132606
TI - An albumin-based theranostic nano-agent for dual-modal imaging guided
photothermal therapy to inhibit lymphatic metastasis of cancer post surgery.
AB - A large variety of cancers are associated with a high incidence of lymph node
metastasis, which leads to a high risk of cancer death. Herein, we demonstrate
that multimodal imaging guided photothermal therapy can inhibit tumor metastasis
after surgery by burning the sentinel lymph nodes (SLNs) with metastatic tumor
cells. A near-infrared dye, IR825, is absorbed onto human serum albumin (HSA),
which is covalently linked with diethylenetriamine pentaacetic acid (DTPA)
molecules to chelate gadolinium. The formed HSA-Gd-IR825 nanocomplex exhibits
strong fluorescence together with high near-infrared (NIR) absorbance, and in the
mean time could serve as a T1 contrast agent in magnetic resonance (MR) imaging.
In vivo bi-modal fluorescence and MR imaging uncovers that HSA-Gd-IR825 after
being injected into the primary tumor would quickly migrate into tumor-associated
SLNs through lymphatic circulation. Utilizing the strong NIR absorbance of HSA-Gd
IR825, SLNs with metastatic cancer cells can be effectively ablated under
exposure to a NIR laser. Such treatment when combined with surgery to remove the
primary tumor offers remarkable therapeutic outcomes in greatly inhibiting
further metastatic spread of cancer cells and prolonging animal survival. Our
work presents an albumin-based theranostic nano-probe with functions of
multimodal imaging and photothermal therapy, together with a 'photothermal
ablation assisted surgery' strategy, promising for future clinical cancer
treatment.
PMID- 25132607
TI - PAIN OUT: the making of an international acute pain registry.
AB - BACKGROUND: About 240 million patients undergo surgery every year, worldwide.
Roughly 50% of these patients report clinically significant pain. Numerous
barriers impede provision of adequate management. Lack of evidence about
appropriateness and effectiveness of interventions is one. A registry can provide
such information, eventually facilitating better management. This paper reports
the development and feasibility of PAIN OUT, the first international acute pain
registry, established with funds from the European Commission, and presents
preliminary analysis to illustrate the nature of investigations that registry
data make possible. METHODS: On the first postoperative day, 6347 adult patients
undergoing orthopaedic or general surgery, in 11 medical centres in Europe and
Israel, provided Patient Reported Outcomes (PROs) using a validated
questionnaire. Clinical data were abstracted from the patient's chart. RESULTS:
Feasibility worked well. Over a period of 1 year, surveyors accrued targeted data
sets and entered them into an online browser. Collaborators could receive online
feedback comparing their findings about PROs against anonymized findings from
other centres. Missing data for the majority of variables were low. Despite
considerable variability between institutions, a large number of patients were
treated according to the generic, evidence-based recommendations we assessed.
However, this was not sufficient to result in acceptable outcomes for the
majority of patients. CONCLUSION: The initial development of PAIN OUT has been
achieved. From 2013, it continues as a not-for-profit academic project, open to
clinicians and researchers worldwide. The International Association for Study of
Pain and PAIN OUT will work together to maintain, disseminate and develop the
registry.
PMID- 25132608
TI - Effects of different sleep deprivation protocols on sleep perception in healthy
volunteers.
AB - OBJECTIVES: To investigate whether different protocols of sleep deprivation
modify sleep perception. METHODS: The effects of total sleep deprivation (TD) and
selective rapid eye movement (REM) sleep deprivation (RD) on sleep perception
were analyzed in normal volunteers. Thirty-one healthy males with normal sleep
were randomized to one of three conditions: (i) normal uninterrupted sleep; (ii)
four nights of RD; or (iii) two nights of TD. Morning perception of total sleep
time was evaluated for each condition. Sleep perception was estimated using total
sleep time (in hours) as perceived by the volunteer divided by the total sleep
time (in hours) measured by polysomnography (PSG). The final value of this
calculation was defined as the perception index (PI). RESULTS: There were no
significant differences among the three groups of volunteers in the total sleep
time measured by PSG or in the perception of total sleep time at baseline
condition. Volunteers submitted to RD exhibited lower sleep PI scores as compared
with controls during the sleep deprivation period (P <0.05). Both RD and TD
groups showed PI similar to controls during the recovery period. CONCLUSION:
Selective REM sleep deprivation reduced the ability of healthy young volunteers
to perceive their total sleep time when compared with time measured by PSG. The
data reinforce the influence of sleep deprivation on sleep perception.
PMID- 25132609
TI - WITHDRAWN: Sleep quality changes in chronically depressed patients treated with
mindfulness-based cognitive therapy or cognitive behavioral analysis system for
psychotherapy: a pilot study.
AB - This article has been withdrawn at the request of the author(s) and/or editor.
The Publisher apologizes for any inconvenience this may cause. The full Elsevier
Policy on Article Withdrawal can be found at
http://www.elsevier.com/locate/withdrawalpolicy.
PMID- 25132610
TI - Sleep architecture in infants with spinal muscular atrophy type 1.
AB - OBJECTIVE: Few reports on sleep patterns of patients with spinal muscular atrophy
type 1 (SMA1) have been published and none on sleep microstructure. The aim of
this study was to analyze sleep architecture and microstructure in a group of
infants with SMA1, compared with age- and sex-matched controls. METHODS: Twelve
SMA1 patients (six males, mean age 5.9 months) and 10 controls (five males, mean
age 4.8 months) underwent full polysomnography to evaluate their sleep
architecture and microstructure by means of the cyclic alternating pattern (CAP).
RESULTS: Compared with control children, SMA1 patients showed increased sleep
latency and apnea/hypopnea index. CAP analysis revealed a significant increase in
the percentage of A1 CAP subtypes, a reduction of that of A3 subtypes and of A2
and A3 indexes (number/h), indicating a dysfunction of the arousal system in
these patients. CONCLUSION: The results indicate the presence of an abnormality
of sleep microstructure in SMA1 patients, characterized by a reduction of A2 and
A3 CAP subtypes. We hypothesize that SMA1 patients have reduced arousability
during non-rapid eye movement sleep, which could be interpreted as additional
evidence of central nervous system involvement in this disease.
PMID- 25132613
TI - Letter to the editor.
PMID- 25132614
TI - Letter to the editor.
PMID- 25132615
TI - Author response.
PMID- 25132616
TI - Picking up myelodysplastic syndromes and megaloblastic anemias on peripheral
blood: use of NEUT-X and NEUT-Y in guiding smear reviews.
PMID- 25132617
TI - Scarless outpatient ablation of pilonidal sinus: a pilot study of a new minimally
invasive treatment.
AB - Pain and secretion of purulent materials are symptoms that are often associated
with the pilonidal sinus. Generally, these symptoms are neglected by patients for
a long time. Patients seek medical attention too late, fearing a prolonged period
of pain and inability after surgery. The optimal therapy for pilonidal sinus
should have the following characteristics: high healing rate, low recurrence
rate, minimal postoperative pain and low cost. The aim of this study is to
explore the effectiveness and safety of a new minimally invasive treatment: the
scarless outpatient ablation of pilonidal sinus (SOAP). A total of 31 consecutive
patients were enrolled; 27 of 31 patients were declared healed after the surgery
(87.09%). After 1 year, only 4 of 27 patients (14.81%) reported symptoms related
to recurrence of the disease. The average duration of the operation was 7.47
minutes. Patients reported the disappearance of painful symptoms after
approximately 2.62 days and had been away from work for 0.53 days. No
complications were recorded during the period of study. The advantages of the
procedure examined in this study are its simplicity and rapidity of execution,
its outpatient setting, its low cost and lack of complications. In our opinion, a
randomised controlled trial should be conducted to validate the results related
to this technique.
PMID- 25132618
TI - Is metformin ready for prime time in pregnancy? Probably not yet.
AB - Metformin is one of the most commonly used drugs to treat type 2 diabetes and is
safe and effective. Its main mechanism of action is thought to be the activation
of AMP-activated protein kinase (AMPK) via inhibition of mitochondrial ATP
generation. Recent use of metformin as an 'insulin sensitizer' in women with
polycystic ovarian syndrome to increase fertility has been successful and
resulted in the chance observation that continued use during pregnancy appeared
to be safe. There are few studies of metformin in animal models of diabetic
pregnancy. However, some data have implicated fetal AMPK activation in neural
tube defects. While a recent report suggests that metformin may not activate
fetal AMPK, which is reassuring, studies in pregnant woman with gestational
diabetes and type 2 diabetes, which are ongoing, require completion before we can
conclude that its use in pregnancy is safe. Furthermore, follow-up of the
offspring will be critical to determine whether such treatment decreases or
increases the development of obesity and diabetes.
PMID- 25132619
TI - Outcomes of haematology/oncology patients admitted to intensive care unit at The
Canberra Hospital.
AB - BACKGROUND: Outcomes for haematology/oncology patients have improved; however,
determining their suitability for intensive care unit (ICU) admission remains
challenging and controversial. AIM: Examine outcomes of patients admitted to an
Australian tertiary hospital ICU and explore potential prognostic factors.
METHODS: A retrospective review of patients with haematological and solid tumour
malignancies non-electively admitted to The Canberra Hospital (TCH) ICU, between
January 2008 and December 2012. Patient demographics, cancer details, reasons for
ICU admission and Acute Physiologic and Chronic Health Evaluation (APACHE) II
scores were collected, and survival rates calculated and correlated with
potential prognostic factors. RESULTS: Of 205 patients, 113 (55%) had
haematological malignancies, and 92 (45%) had solid tumours: 58% male and mean
age 60.3 years (standard deviation (SD) 13.4). Eighty-two per cent of solid
tumour patients had metastatic disease and 55% received palliative chemotherapy.
Primary reasons for ICU admission included sepsis (59%), respiratory distress
(37%) and hypotension/shock (18%). Mean APACHE II score was 20.1(SD 0.55); mean
length of stay in ICU, 4 days (SD 5.2); ICU survival was 76% with 62% and 41%
alive at 30 days and 6 months respectively. Overall 1-year survival was 36%. High
APACHE II scores and >=2 organs failing were significant risk factors for 30-day
mortality. CONCLUSION: Short-term outcomes were similar to contemporary studies
from a general tertiary hospital setting and better than historical data. Sixty
two per cent of patients were alive 30 days post-ICU admission, with a
significant minority alive at 12 months, confirming some patients achieved
worthwhile outcomes. Further research is needed to ensure appropriate patient
selection and to explore quality of life post ICU.
PMID- 25132620
TI - In vivo 1H MRS of human gallbladder bile at 3 T in one and two dimensions:
detection and quantification of major biliary lipids.
AB - In vitro (1)H MRS of human bile has shown potential in the diagnosis of various
hepatopancreatobiliary (HPB) diseases. Previously, in vivo (1)H MRS of human bile
in gallbladder using a 1.5 T scanner demonstrated the possibility of
quantification of choline-containing phospholipids (chol-PLs). However, other
lipid components such as bile acids play an important role in the pathophysiology
of the HPB system. We have employed a higher magnetic field strength (3 T), and a
custom-built receive array coil, to improve the quality of in vivo (1)H MRS of
human bile in the gallbladder. We obtained significant improvement in the quality
of 1D spectra (17 healthy volunteers) using a respiratory-gated PRESS sequence
with well distinguished signals for total bile acids (TBAs) plus cholesterol
resonating at 0.66 ppm, taurine-conjugated bile acids (TCBAs) at 3.08 ppm, chol
PLs at 3.22 ppm, glycine-conjugated bile acids (GCBAs) at 3.74 ppm, and the amide
proton (-NH) arising from GCBAs and TCBAs in the region 7.76-8.05 ppm. The peak
areas of these signals were measured by deconvolution, and subsequently the molar
concentrations of metabolites were estimated with good accuracy, except for that
of TBAs plus cholesterol. The concentration of TBAs plus cholesterol was
overestimated in some cases, which could be due to lipid contamination. In
addition, we report the first 2D L-COSY spectra of human gallbladder bile in vivo
(obtained in 15 healthy volunteers). 2D L-COSY spectra will be helpful in
differentiating various biliary chol-PLs in pathological conditions of the HPB
system.
PMID- 25132621
TI - Abusive supervision and links to nurse intentions to quit.
AB - PURPOSE: To investigate forms of abusive supervision, namely personal attacks,
task attacks, and isolation, and their links to outcomes for nurses, including
job satisfaction, psychological strain, and intentions to quit. DESIGN: Cross
sectional survey design. Data collected from July to November 2012. METHODS: Two
hundred and fifty public sector nurses employed at five general acute Australian
hospitals completed the survey (response rate of 33%). FINDINGS: Structural
equation modeling on the forms of abusive supervision (personal, task, isolation)
and nurse outcomes indicated goodness of fit statistics that confirmed a well
fitting model, explaining 40% of the variance in intent to quit, 30% in job
satisfaction, and 33% in strain. An indirect relationship from personal attacks
to intentions to quit, via strain, was observed. Task attacks were related
directly, and indirectly via job satisfaction, to increased intentions to quit.
Surprisingly, isolation was positively related to job satisfaction. CONCLUSIONS:
Abusive supervision impacted nurse outcomes. Specifically, personal abuse had
personal and health impacts; work-focused abuse had work-oriented effects.
Applying appraisal theory suggests that personal attacks are primarily assessed
as stressful and unchangeable; task-oriented attacks are assessed as stressful,
but changeable; and isolation is assessed as benign. The findings highlight the
impact of abusive supervision, especially task attacks, on outcomes important to
nurse retention. CLINICAL RELEVANCE: The findings can be used to devise programs
to educate, train, and support supervisors and their subordinates to adhere to
zero tolerance policies toward antisocial workplace behaviors and encourage
reporting incidents.
PMID- 25132623
TI - The role of a nanoparticle monolayer on the flow of polymer melts in
nanochannels.
AB - Understanding and controlling the flow properties of polymer melts at the
nanoscale is of great relevance in fundamental research and in a variety of
applications. In the present study we have analysed experimentally the flow
behaviour of polymers in nanochannels of varying roughness, produced by gold
nanoparticle absorption. The experimental results show that nanochannel roughness
has a significant influence on surface energy and on the flow behaviour of
polymer melts. These results provide fundamental information on the preparation
of one-dimensional polymer nanochannels applicable in both micro- and nano
injection technology.
PMID- 25132622
TI - Patient preferences for treatments to delay bone metastases.
AB - BACKGROUND: Most patients with advanced prostate cancer (PCa) develop bone
metastases (BM) and present with bone complications like fracture. Bone-targeted
agents that prevent metastasis-induced bone complications can cause adverse
events. Understanding how patients view treatment options may optimize care. This
study aimed to quantify how PCa patients value a hypothetical treatment that
delays BM but can cause osteonecrosis of the jaw (ONJ). The study also assessed
the value patients place on avoiding metastasis-induced bone complications versus
increased survival. METHODS: PCa patients from the United Kingdom (n = 201) and
Sweden (n = 200) on androgen-deprivation therapy or hormone therapy for >= 3
years completed a 10-question discrete-choice-experiment survey examining whether
patients would accept a BM-delaying treatment. Two time-tradeoff questions
assessed patients' willingness to tradeoff between survival and bone
complications. Percentages of patients choosing treatment were summarized by
levels of treatment efficacy and ONJ risk. Odds ratios from a logit model were
used to evaluate how patient and medication characteristics affected treatment
choice. Proportions of patients choosing each tradeoff scenario were calculated.
RESULTS: A majority of patients accepted treatment at the lowest benefit level (5
month BM delay) and highest risk level (9% ONJ risk). PCa symptoms and prior
treatment affected patient preferences. Nearly 80% of patients would tradeoff at
least 3 months of survival to avoid bone complications. CONCLUSIONS: PCa patients
in the U.K and Sweden may value a medication that delays BM, despite the risk of
ONJ. Furthermore, patients were willing to tradeoff up to 5 months of survival
for prevention of bone complications.
PMID- 25132624
TI - Physiological and biochemical responses of three Veneridae clams exposed to
salinity changes.
AB - Given their global importance, coastal marine environments are a major focus of
concern regarding the potential impacts of climate change, namely due to
alterations in seawater salinity. It is known that environmental characteristics,
such as salinity, affect immune and physiological parameters of bivalves.
Nevertheless, scarce information is available concerning the biochemical
alterations associated with salinity changes. For this reason, the present work
aimed to evaluate the biochemical responses of three venerid clam species
(Venerupis decussata, Venerupis corrugata, Venerupis philippinarum) submitted to
salinity changes. The effects on the native (V. decussata and V. corrugata) and
invasive (V. philippinarum) species collected from the same sampling site and
submitted to the same salinity gradient (0 to 42g/L) were compared. The results
obtained demonstrated that V. corrugata is the most sensitive species to salinity
changes and V. decussata is the species that can tolerate a wider range of
salinities. Furthermore, our work showed that clams under salinity associated
stress can alter their biochemical mechanisms, such as increasing their
antioxidant defenses, to cope with the higher oxidative stress resulting from
hypo and hypersaline conditions. Among the physiological and biochemical
parameters analyzed (glycogen and protein content; lipid peroxidation levels,
antioxidant enzymes activity; total, reduced and oxidized glutathione) Catalase
(CAT) and especially superoxide dismutase (SOD) showed to be useful biomarkers to
assess salinity impacts in clams.
PMID- 25132625
TI - Dynamic switching of the circularly polarized luminescence of disubstituted
polyacetylene by selective transmission through a thermotropic chiral nematic
liquid crystal.
AB - The circularly polarized luminescence (CPL) of chiral disubstituted liquid
crystalline polyacetylene (di-LCPA) can be dynamically switched and amplified
from left- to right-handed CPL and vice versa through the selective transmission
of CPL across a thermotropic chiral nematic liquid crystal (N*-LC) phase. By
combining a chiral di-LCPA CPL-emitting film with an N*-LC cell and tuning the
selective reflection band of the N*-LC phase to coincide with the CPL emission
band, a CPL-switchable cell was constructed. The phase change induced by the
thermotropic N*-LC cell by varying the temperature leads to a change in the
selective transmission of CPL, which enables the dynamic switching and
amplification of CPL. It is anticipated that CPL-switchable devices might find
applications in switchable low-threshold lasers and optical memory devices.
PMID- 25132628
TI - Repeal of the Sustainable Growth Rate: an overview for surgeons.
AB - BACKGROUND: The Medicare sustainable growth rate (SGR) formula is used to control
Medicare spending on physician services. Under the current SGR formula,
physicians face an almost 24% cut to the Medicare fee schedule on April 1, 2015.
The US House Way & Means and Energy & Commerce Committees and the Senate Finance
Committee released jointly proposed legislation to permanently repeal the SGR,
and transition Medicare physician payment to a value-based payment method. This
review summarizes the key components of the proposed legislation, and discusses
some of the political challenges ahead. DATA SOURCES: House Committees on Energy
& Commerce and Ways & Means, and the Senate Committee on Finance staff write-ups.
CONCLUSIONS: Physician Medicare reimbursement will move from a volume-based model
to a value-based model over the next decade. Surgeons should remain engaged with
the political process to ensure repeal of the SGR.
PMID- 25132627
TI - Management of the pediatric spontaneous pneumothorax: is primary surgery the
treatment of choice?
AB - BACKGROUND: Surgery as the primary management strategy for pediatric primary
spontaneous pneumothorax is controversial. This study aims to evaluate the
outcomes and effectiveness of management approaches for pediatric spontaneous
pneumothorax. METHODS: Outcomes of pediatric patients undergoing initial
nonoperative treatment versus video-assisted thoracoscopic surgery with
blebectomy and mechanical pleurodesis were compared via a retrospective review.
RESULTS: We identified 96 patients with 108 pneumothoraces. Of 98 pneumothoraces
with initial nonoperative management, 37% had surgery during their initial
hospitalization for persistent air leak. Of those discharged home without video
assisted thoracoscopic surgery, 40% recurred. Initial nonoperative management
resulted in more total hospital days (median: 11 vs 5 days, P < .001). No
significant predictors of recurrence were identified on multivariate analysis.
Sixty-three percent of all patients ultimately required surgery. CONCLUSIONS:
Fewer than 40% of primary spontaneous pneumothorax patients are definitively
treated with nonoperative management. A prospective study is needed to determine
whether primary surgery with blebectomy/mechanical pleurodesis is a more
effective treatment strategy.
PMID- 25132629
TI - Invited commentary on "Evaluation of a predictive model for pancreatic fistula
based on amylase value in drains after pancreatic resection" by Partelli et al.
PMID- 25132626
TI - Infant perceptual development for faces and spoken words: an integrated approach.
AB - There are obvious differences between recognizing faces and recognizing spoken
words or phonemes that might suggest development of each capability requires
different skills. Recognizing faces and perceiving spoken language, however, are
in key senses extremely similar endeavors. Both perceptual processes are based on
richly variable, yet highly structured input from which the perceiver needs to
extract categorically meaningful information. This similarity could be reflected
in the perceptual narrowing that occurs within the first year of life in both
domains. We take the position that the perceptual and neurocognitive processes by
which face and speech recognition develop are based on a set of common
principles. One common principle is the importance of systematic variability in
the input as a source of information rather than noise. Experience of this
variability leads to perceptual tuning to the critical properties that define
individual faces or spoken words versus their membership in larger groupings of
people and their language communities. We argue that parallels can be drawn
directly between the principles responsible for the development of face and
spoken language perception.
PMID- 25132630
TI - Flow cytometry detection of minimal residual disease in multiple myeloma: Lessons
learned at FDA-NCI roundtable symposium.
PMID- 25132631
TI - Bridging of anions by hydrogen bonds in nest motifs and its significance for
Schellman loops and other larger motifs within proteins.
AB - The nest is a protein motif of three consecutive amino acid residues with
dihedral angles 1,2-alphaR alphaL (RL nests) or 1,2-alphaL alphaR (LR nests).
Many nests form a depression in which an anion or delta-negative acceptor atom is
bound by hydrogen bonds from the main chain NH groups. We have determined the
extent and nature of this bridging in a database of protein structures using a
computer program written for the purpose. Acceptor anions are bound by a pair of
bridging hydrogen bonds in 40% of RL nests and 20% of LR nests. Two thirds of the
bridges are between the NH groups at Positions 1 and 3 of the motif (N1N3
bridging)-which confers a concavity to the nest; one third are of the N2N3 type
which does not. In bridged LR nests N2N3-bridging predominates (14% N1N3: 75%
N2N3), whereas in bridged RL nests the reverse is true (69% N1N3: 25% N2N3). Most
bridged nests occur within larger motifs: 45% in (hexapeptide) Schellman loops
with an additional 4 -> 0 hydrogen bond (N1N3), 11% in Schellman loops with an
additional 5 -> 1 hydrogen bond (N2N3), 12% in a composite structure including a
type 1beta-bulge loop and an asx- or ST- motif (N1N3)-remarkably homologous to
the N1N3-bridged Schellman loop-and 3% in a composite structure including a type
2beta-bulge loop and an asx-motif (N2N3). A third hydrogen bond is a previously
unrecognized feature of Schellman loops as those lacking bridged nests have an
additional 4 -> 0 hydrogen bond.
PMID- 25132632
TI - Environmental azole fungicide, prochloraz, can induce cross-resistance to medical
triazoles in Candida glabrata.
AB - Acquisition of azole resistance by clinically relevant yeasts in nature may
result in a significant, yet undetermined, impact in human health. The main goal
of this study was to assess the development of cross-resistance between
agricultural and clinical azoles by Candida spp. An in vitro induction assay was
performed, for a period of 90 days, with prochloraz (PCZ) - an agricultural
antifungal. Afterward, the induced molecular resistance mechanisms were unveiled.
MIC value of PCZ increased significantly in all Candida spp. isolates. However,
only C. glabrata developed cross-resistance to fluconazole and posaconazole. The
increased MIC values were stable. Candida glabrata azole resistance acquisition
triggered by PCZ exposure involved the upregulation of the ATP binding cassette
multidrug transporter genes and the transcription factor, PDR1. Single mutation
previously implicated in azole resistance was found in PDR1 while ERG11 showed
several synonymous single nucleotide polymorphisms. These results might explain
why C. glabrata is so commonly less susceptible to clinical azoles, suggesting
that its exposure to agricultural azole antifungals may be associated to the
emergence of cross-resistance. Such studies forward potential explanations for
the worldwide increasing clinical prevalence of C. glabrata and the associated
worse prognosis of an infection by this species.
PMID- 25132633
TI - Numerical investigations of the haemodynamic changes associated with stent
malapposition in an idealised coronary artery.
AB - The deployment of a coronary stent near complex lesions can sometimes lead to
incomplete stent apposition (ISA), an undesirable side effect of coronary stent
implantation. Three-dimensional computational fluid dynamics (CFD) calculations
are performed on simplified stent models (with either square or circular cross
section struts) inside an idealised coronary artery to analyse the effect of
different levels of ISA to the change in haemodynamics inside the artery. The
clinical significance of ISA is reported using haemodynamic metrics like wall
shear stress (WSS) and wall shear stress gradient (WSSG). A coronary stent with
square cross-sectional strut shows different levels of reverse flow for
malapposition distance (MD) between 0mm and 0.12 mm. Chaotic blood flow is
usually observed at late diastole and early systole for MD=0mm and 0.12 mm but
are suppressed for MD=0.06 mm. The struts with circular cross section delay the
flow chaotic process as compared to square cross-sectional struts at the same MD
and also reduce the level of fluctuations found in the flow field. However,
further increase in MD can lead to chaotic flow not only at late diastole and
early systole, but it also leads to chaotic flow at the end of systole. In all
cases, WSS increases above the threshold value (0.5 Pa) as MD increases due to
the diminishing reverse flow near the artery wall. Increasing MD also results in
an elevated WSSG as flow becomes more chaotic, except for square struts at
MD=0.06 mm.
PMID- 25132634
TI - Microsporidiosis in pediatric renal transplant patients in Cape Town, South
Africa: two case reports.
AB - Microsporidia are an emerging group of pathogens associated with life-threatening
opportunistic infections in immunocompromised hosts, particularly human
immunodeficiency virus (HIV)-infected individuals. There have, however, been
recent reports of infection in adult solid organ transplant recipients. We report
two cases in children, to our knowledge the first in the paediatric literature.
Two 13-yr-old, HIV-seronegative females received deceased donor renal transplants
from the same donor. Both patients suffered acute cell-mediated rejection and CMV
infection reactivation, managed with intensified immunosuppression and
ganciclovir. Pyrexia of unknown origin and intermittent diarrhea in both prompted
extensive investigations. In both patients, numerous spores of a microsporidial
species were demonstrated in renal tissue on biopsy and in the urine, using
modified trichrome and quick-hot Gram-chromotrope staining. Electron microscopy
and PCR confirmed Encephalitozoon cuniculi infections. Both patients were
successfully treated with 400 mg twice daily of albendazole, with sustained
clinical improvement. We recommend that microsporidiosis be considered in the
differential diagnosis of pyrexia of unknown origin in severely immunocompromised
pediatric solid organ transplant recipients, particularly when associated with
diarrhea.
PMID- 25132635
TI - Citrate versus heparin for apheresis catheter locks: an efficacy analysis.
AB - INTRODUCTION: There is a paucity of medical literature regarding the efficacy of
lock solutions in preventing catheter thrombosis. Traditionally, heparin has been
used as the anticoagulant of choice for catheter locking, but it has many adverse
effects associated with its use. Sodium citrate 4% is an attractive alternative
to heparin. METHODS: Our plasmapheresis unit converted to locking all central
venous catheters with sodium citrate 4% in place of heparin 100 units/mL in May
2010. We conducted a 2-year period retrospective observational cohort study
comparing the outcomes of using heparin versus citrate locks. Outcomes examined
were catheter patency, catheter exchanges, alteplase usage, and catheter
infections. RESULTS: During the study period, 84 patients who underwent a total
of 554 plasmapheresis treatments were identified. Flow problems among the citrate
treatments were more frequent than those among the heparin group (6.5% vs. 3.2%,
P = 0.11, n = 554) but this did not reach statistical significance. The frequency
of more severe flow problems requiring catheter exchange or alteplase infusion
was higher among the citrate group than the heparin group (3.2% vs. 1.3%, P =
0.11, n = 554). Subgroup analysis, stratified by diagnosis, demonstrated that
there was a statistically significant difference in flow problems when comparing
myasthenia gravis (MG) patients to non-MG patients. There was no difference in
catheter infections between the groups. CONCLUSIONS: Based on the findings of our
study, we conclude that citrate and heparin locks have similar efficacy in
maintaining catheter patency in plasmapheresis patients. Further research is
needed to examine the differences observed between MG patients versus all other
patients.
PMID- 25132636
TI - Mechanical properties and microstructure analysis of mineral trioxide aggregate
mixed with hydrophilic synthetic polymer.
AB - INTRODUCTION: In dentistry, mineral trioxide aggregate (MTA) has been widely used
for root perforation, retrograde filling, pulp capping and regenerative
endodontics. Despite its superior sealing ability and biocompatibility, MTA has
critical drawbacks regarding handling property such as sandy property, lacking
cohesive properties and wash-out tendency. So, it is necessary to improve the
fluidity of MTA in order to improve its handling properties. In this study, we
applied modified liquid to improve handling properties of MTA. METHODS: Polyvinyl
alcohol (PVA; 3 and 5 wt %) aqueous solutions were prepared and the samples were
divided into three groups: DW group (MTA mixed with distilled water), P3 group
(MTA mixed with 3% PVA), and P5 group (MTA mixed with 5% PVA). Handling property,
initial setting time, and compressive strength were evaluated. The
microstructures were observed by Field emission scanning electron microscope (FE
SEM) and X-ray diffractometer (XRD) phase analyses were performed. RESULTS: PVA
modified group showed similar behavior of IRM compared to DW group. The initial
setting time of P3 or P5 group was significantly longer than that of DW group (p
< 0.05). The compressive strength of DW group was higher than that of P3 or P5
groups (p < 0.05). Experimental groups (P3 and P5) showed no microstructural
differences compared with DW group when the fractured surfaces were observed by
FE-SEM with XRD patterns after 3 and 14 days. CONCLUSIONS: Polyvinyl alcohol, a
modified liquid for MTA, improved the handling properties of the material without
violating its microstructure.
PMID- 25132637
TI - Photoinitiated [corrected] charge separation in a hybrid titanium dioxide
metalloporphyrin peptide material.
AB - In natural systems, electron flow is mediated by proteins that spatially organize
donor and acceptor molecules with great precision. Achieving this guided,
directional flow of information is a desirable feature in photovoltaic media.
Here, we design self-assembled peptide materials that organize multiple
electronic components capable of performing photoinduced charge separation. Two
peptides, c16-AHL3K3-CO2H and c16-AHL3K9-CO2H, self-assemble into fibres and
provide a scaffold capable of binding a metalloporphyrin via histidine axial
ligation and mineralize titanium dioxide (TiO2) on the lysine-rich surface of the
resulting fibrous structures. Electron paramagnetic resonance studies of this
self-assembled material under continuous light excitation demonstrate charge
separation induced by excitation of the metalloporphyrin and mediated by the
peptide assembly structure. This approach to dye-sensitized semiconducting
materials offers a means to spatially control the dye molecule with respect to
the semiconducting material through careful, strategic peptide design.
PMID- 25132638
TI - Bionanotechnology: arrays in the future prospects of the field.
PMID- 25132639
TI - Molecular fingerprint similarity search in virtual screening.
AB - Molecular fingerprints have been used for a long time now in drug discovery and
virtual screening. Their ease of use (requiring little to no configuration) and
the speed at which substructure and similarity searches can be performed with
them - paired with a virtual screening performance similar to other more complex
methods - is the reason for their popularity. However, there are many types of
fingerprints, each representing a different aspect of the molecule, which can
greatly affect search performance. This review focuses on commonly used
fingerprint algorithms, their usage in virtual screening, and the software
packages and online tools that provide these algorithms.
PMID- 25132640
TI - SFAPS: an R package for structure/function analysis of protein sequences based on
informational spectrum method.
AB - The R package SFAPS has been developed for structure/function analysis of protein
sequences based on information spectrum method. The informational spectrum method
employs the electron-ion interaction potential parameter as the numerical
representation for the protein sequence, and obtains the characteristic frequency
of a particular protein interaction after computing the Discrete Fourier
Transform for protein sequences. The informational spectrum method is often used
to analyze protein sequences, so we developed this software tool, which is
implemented as an add-on package to the freely available and widely used
statistical language R. Our package is distributed as open source code for Linux,
Unix and Microsoft Windows. It is released under the GNU General Public License.
The R package along with its source code and additional material are freely
available at http://mlsbl.tongji.edu.cn/DBdownload.asp.
PMID- 25132641
TI - Predictors and incidence of post-partum depression: a longitudinal cohort study.
AB - AIM: This study was designed to identify the incidence and the related factors
contributing to post-partum depression (PPD) in women in Iran for the first time.
MATERIAL AND METHODS: A total of 2279 eligible pregnant women from 32-42 weeks of
pregnancy to 12 weeks post-partum (2009) who attended primary health centers in
Mazandaran province were screened for depression using the Iranian version of the
Edinburgh Postnatal Depression Scale. Pregnant women free from depression were
assessed using validated questionnaires, including the Premenstrual Syndrome
Questionnaire, Social Support Appraisal Scale, Network Orientation Scale, General
Health Questionnaire, Marital Inventory, Life Events Rating Scale and Parental
Expectation Survey. Logistic regression analysis was used to determine the risk
factors of PPD. RESULTS: Of 1801 women who screened negative for depression at 32
42 weeks' gestation, cumulative incidence proportions were 6.7%, 4.3% and 4.5%
during 0-2, >2-8 and >8-12 weeks post-partum, respectively. The factors
predictive of PPD were: history of depression during the first two trimesters of
pregnancy (odds ratio [OR] = 2.55, 95% confidence interval [CI] = 1.59-4.1);
psychiatric disorder during pregnancy (OR = 1.08, 95%CI = 1.06-1.11); gestational
diabetes (OR = 2.93, 95%CI = 1.46-5.88); recurrent urinary infection (OR = 2.25,
95%CI = 1.44-3.52); unwanted pregnancy (OR = 2.5, 95%CI = 1.69-3.7) and low
household income (OR = 3.57, 95%CI = 1.49-8.5). The risk was decreased with
increasing age (OR = 0.88, 95%CI = 0.84-0.92) and those with high self-efficacy
for mothering (OR = 0.7, 95%CI = 0.62-0.78). CONCLUSION: A high rate of new cases
of PPD was identified in Iranian women. A combination of psychological,
sociological, obstetric and sociodemographic factors can render mothers
vulnerable to post-partum depression.
PMID- 25132643
TI - Mechanism of 2',3'-dimethoxyflavanone-induced apoptosis in breast cancer stem
cells: role of ubiquitination of caspase-8 and LC3.
AB - Accumulating evidence has displayed that targeting cancer stem cells (CSCs) is a
very promising way for anti-cancer therapies. 2',3'-Dimethoxyflavanone (2',3'
DMF) showed the most potent toxicity of a group of 42 flavonoids tested in MCF-7
SC breast cancer stem cells. 2',3'-DMF triggered intrinsic and extrinsic
apoptosis by stimulating the cleavage of PARP and the activation of caspase-9,
8, and -3. Interestingly, 2',3'-DMF induces a dramatic increase in the conversion
of LC3, a well-known marker for autophagy. However, acidic vesicular organelles
(AVOs), one of the autophagic flux markers were not detected. Co-treatment with
chloroquine, the lysosomal inhibitor that blocks autophagic degradation did not
show any change in the degree of LC3 conversion, implying that LC3 could play a
role in the non-autophagic cell death of MCF-7-SC. We found that 2',3'-DMF
induces the ubiquitination of caspase-8, this resulted in an interaction between
caspase-8 and LC3, which led to the aggregation and activation of caspase-8. Co
treating cells with 2',3'-DMF and 3-methyladenine, an inhibitor of LC3
lipidation, reduced the activation of caspase-8. These findings provide novel
insights into the anti-cancer effects of 2',3'-DMF in breast cancer stem cells by
revealing that it induced apoptosis in accompany with the activation of caspase-8
mediated by LC3 conversion.
PMID- 25132642
TI - Targeting melanocyte and melanoma stem cells by 8-hydroxy-2
dipropylaminotetralin.
AB - Monobenzyl ether of hydroquinone (MBEH) is cytotoxic towards melanocytes. Its
treatment efficacy is limited by an inability to eradicate stem cells. By
contrast, 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-DPAT) affects melanocyte stem
cell survival. MBEH and 8-DPAT were added to melanocytes and melanoma cells to
compare cytotoxicity. Stem cell content among viable cells was determined by
fluorocytometry using markers CD34, Pax3, and CD271. Immunostaining was used to
identify stem cells in skin explants treated with MBEH or 8-DPAT ex vivo. Mice
were exposed to MBEH or 8-DPAT and scanned for depigmentation before harvesting
skin. MBEH exposure prompted a relative increase in stem cells among cultured
melanocytes and melanoma cells, as treatment preferentially eliminated
differentiated cells and spared the stem cells. Viability of this remaining,
enriched stem cell population was however rapidly reduced by exposure to 8-DPAT
within melanocyte and melanoma cell cultures. In human skin explants, the
abundance of melanocyte stem cells was also visibly reduced after 8-DPAT
treatment, in contrast to tissue exposed to MBEH. Meanwhile, significant
depigmentation of the mouse pelage and loss of differentiated melanocytes was
observed in vivo in response to topical application of MBEH, but not 8-DPAT.
Prolonged application of the latter agent instead appeared to effectively reduce
the abundance of melanocyte stem cells in the dermis. This furthers the idea that
MBEH and 8-DPAT target complementary cell populations. Results indicate that
combination treatment may demonstrate superior therapeutic activity by
eliminating both differentiated and tumor initiating populations.
PMID- 25132644
TI - Hyper-coupling between working memory task-evoked activations and amplitude of
spontaneous fluctuations in first-episode schizophrenia.
AB - Working memory (WM) deficit is an important component of impaired cognition in
schizophrenia. However, between-studies inconsistencies as to the specific
functional substrate imply that inter-individual variability (IIV) in the WM
performance is associated with IIV in brain activity in schizophrenia. To examine
the neural substrate of this WM IIV, we studied whether the neural mechanisms
that underlie individual differences in WM capacity are the same in schizophrenia
patients and healthy people. We correlated the IIV of the task-evoked brain
activity and task performance during an n-back WM task with the IIV of the moment
to-moment variability in intrinsic resting-state activity, as measured by the
amplitude of low-frequency fluctuations (ALFFs) and further compared this
relationship between 17 patients with first-episode schizophrenia (FES) and 18
healthy controls. Between-group comparisons of the correlation patterns indicated
aberrant ALFF-WM activation correlations and ALFF-WM performance correlations in
the FES patients, but no significant changes were detected in any single
measurement of these three characteristics. Specifically, we found increased
positive ALFF-WM activation correlations in the bilateral lateral prefrontal
cortices, posterior parietal cortices and fusiform gyri in the FES patients. We
also observed significant increases in positive ALFF-WM performance correlations
in the bilateral ventromedial prefrontal cortices in the FES patients. This hyper
coupling between the ALFF and fMRI measures during a WM task may indicate that it
was difficult for the patients to detach themselves from one state to transition
to another and suggests that the inefficient cortical function in schizophrenia
stems from the intrinsic functional architecture of the brain.
PMID- 25132645
TI - Oncoplastic mammaplasty with geometric compensation--a technique for breast
conservation.
AB - OBJECTIVE: To describe a technique of oncoplastic mammaplasty, referred to as
geometric compensation, which is suitable for tumors close to the skin in areas
not included in the classic preoperative drawings for mammaplasty. MATERIALS AND
METHODS: Seventeen patients with malignant tumors were included. Preoperative
markings followed the "Wise-pattern" technique. The resection of affected skin
was geometrically compensated with another area of preserved skin. RESULTS: The
mean age of the patients was 52.88 +/- 12.14 years. Mean pathological tumor size
was 43.82 +/- 31.39 mm. There were 7 (41.18%) locally advanced tumors. Six
patients (35.29%) were submitted to neoadjuvant and the remainder to adjuvant
chemotherapy. Radiotherapy was indicated in all cases. Fifteen patients (88.24%)
received hormone therapy. Ptosis was corrected in all cases. The aesthetic result
was rated excellent in seven cases (41.18%), good in 7 (41.18%), and fair in
three cases (17.65%). Surgical margins were free. A seroma developed in one case
(5.88%), small fat necrosis in three (17.65%), and enlarged scar in one (5.88%).
There were no recurrences within 28.24 +/- 18.02 months. CONCLUSIONS: The
technique allowed breast conservation in situations requiring large resection of
affected skin, with free surgical margins, correction of ptosis, satisfactory
symmetry, and few complications.
PMID- 25132646
TI - Upper bounds on FST in terms of the frequency of the most frequent allele and
total homozygosity: the case of a specified number of alleles.
AB - FST is one of the most frequently-used indices of genetic differentiation among
groups. Though FST takes values between 0 and 1, authors going back to Wright
have noted that under many circumstances, FST is constrained to be less than 1.
Recently, we showed that at a genetic locus with an unspecified number of
alleles, FST for two subpopulations is strictly bounded from above by functions
of both the frequency of the most frequent allele (M) and the homozygosity of the
total population (HT). In the two-subpopulation case, FST can equal one only when
the frequency of the most frequent allele and the total homozygosity are 1/2.
Here, we extend this work by deriving strict bounds on FST for two subpopulations
when the number of alleles at the locus is specified to be I. We show that
restricting to I alleles produces the same upper bound on FST over much of the
allowable domain for M and HT, and we derive more restrictive bounds in the
windows M?[1/I,1/(I-1)) and HT?[1/I,I/(I(2)-1)). These results extend our
understanding of the behavior of FST in relation to other population-genetic
statistics.
PMID- 25132648
TI - Oxygen sensing and metabolic homeostasis.
AB - Oxygen-sensing mechanisms have evolved to maintain cell and tissue homeostasis
since the ability to sense and respond to changes in oxygen is essential for
survival. The primary site of oxygen sensing occurs at the level of the carotid
body which in response to hypoxia signals increased ventilation without the need
for new protein synthesis. Chronic hypoxia activates cellular sensing mechanisms
which lead to protein synthesis designed to alter cellular metabolism so cells
can adapt to the low oxygen environment without suffering toxicity. The master
regulator of the cellular response is hypoxia-inducible factor (HIF). Activation
of this system under condition of hypobaric hypoxia leads to weight loss
accompanied by increased basal metabolic rate and suppression of appetite. These
effects are dose dependent, gender and genetic specific, and results in adverse
effects if the exposure is extreme. Hypoxic adipose tissue may represent a
unified cellular mechanism for variety of metabolic disorders, and insulin
resistance in patients with metabolic syndrome.
PMID- 25132647
TI - The expression of aminoacyl-tRNA-synthetase-interacting multifunctional protein-1
(Aimp1) is regulated by estrogen in the mouse uterus.
AB - Aimp1 is known as a multifunctional cytokine in various cellular events. Recent
study showed Aimp1 is localized in glandular epithelial, endothelial, and stromal
cells in functionalis and basalis layers of the endometrium. However, the
regulatory mechanism of Aimp1 in the uterus remains unknown. In the present
study, we found that Aimp1 is expressed in the mouse uterus. Aimp1 transcripts
were decreased at diestrus stage. However, the level of Aimp1 protein was
significantly increased in the luminal epithelium in the uterine endometrium at
estrus stage during the estrous cycle. We found that treatment of estrogen
increased the expression of Aimp1 in the uterus in ovarectomized mice. We
identified one estrogen receptor binding element (ERE) on mouse Aimp1 promoter.
The activity of Aimp1 promoter was increased with estrogen treatment. Our
findings indicate that Aimp1 might act as an important regulator to remodel the
uterine endometrium and its expression might be regulated by estrogen during the
estrous cycle. This will give us better understanding of the dynamic change of
uterine remodeling during the estrous cycle.
PMID- 25132649
TI - The three-factor structure of the Levenson self-report psychopathy scale: fool's
gold or true gold? A study in a sample of Italian adult non-clinical
participants.
AB - The major aim of this study was to evaluate the factor structure of the Italian
translation of the Levenson Self-Report Psychopathy Scale (LSRP) in a sample of
740 community dwelling adult participants. Hull method, minimum average partial
analysis and quasi-inferential parallel analysis techniques were used to identify
a three-factor solution that appeared broadly consistent with previous work. The
three factors exhibited reliability coefficients >0.70, and the three-factor
structure was adequately reproduced across gender, educational level and civil
status strata (median congruence coefficients = 0.94, 0.93 and 0.95 respectively)
and remained largely unchanged when the effect of participants' age was
controlled for (median factor score correlation = 0.99). Although Factor 3 in our
study was demarcated mainly by reverse-keyed items, the LSRP factors yielded
meaningful relations with retrospective measures of antisocial behaviour in
adolescence and HEXACO personality traits and were conceptually consistent with
the triarchic model of psychopathy of Patrick, Fowles and Krueger (2009).
PMID- 25132650
TI - Prophylactic stretching is unlikely to prevent nocturnal leg cramps.
PMID- 25132651
TI - Depression and psychosocial correlates of liver transplant candidates: a
systematic review.
AB - INTRODUCTION: Liver transplant candidates are vulnerable to develop depression.
This paper aims to ascertain the prevalence of depression in liver transplant
candidates and its psychosocial factors in a systematic review. METHODS: An
extensive review via electronic databases (PubMed, EMBASE, CINAHL) and hand
search were carried out to retrieve published articles up to December 15, 2013,
using (Incidence OR Prevalence) AND Depress* AND liver transplant as the
keywords. Information on the study design, patient characteristics, prevalence of
depression, and its associated risk factors were extracted from included studies.
RESULTS: There were 22 studies included in this review with a total of 3055
patients. The prevalence of depression in the liver transplant candidates ranges
between 2% and 80%. Studies that used diagnostic tools found a narrower range of
prevalence (4.5-43%) as compared to the self-administered questionnaires (2-80%).
Studies that used Beck Depression Inventory reported a higher prevalence than
those studies which used Hospital Anxiety and Depression Scale (median = 28%,
range = 2-80% versus median 17%, range 6.1-25.8%). A number of socio-demographic
factors, illness-related and psychosocial factors were found to be associated
with depression. CONCLUSION: Prevalence of depression in liver transplant
candidates is high, and early detection will improve survival and quality of
life.
PMID- 25132652
TI - Distinct driver mutation profiles of childhood and adolescent essential
thrombocythemia.
PMID- 25132654
TI - Effect of thrombopoietin receptor agonists on the apoptotic profile of platelets
in patients with chronic immune thrombocytopenia.
AB - Platelet survival depends upon mediators of apoptosis e.g., Bcl-xL, Bax, and Bak,
which are regulated by thrombopoietin (TPO)-mediated AKT signaling.
Thrombopoietin receptor (TPO-R) signaling might decrease platelet and/or
megakaryocyte apoptosis and increase the platelet count. This study therefore
explored anti-apoptotic effects of TPO-R-agonists in vivo on platelets of
patients with immune thrombocytopenia. Patients received eltrombopag or
romiplostim for two weeks. Total, immature, and large platelet counts were
assessed as were Bcl-xL inhibitor assay; Bcl-xL Western blot; and flow cytometric
(FACS) analysis of the AKT-signaling pathway. Eight/ten patients had platelet
responses to eltrombopag and all three to romiplostim. Platelet sensitivity to
apoptosis by Bcl-xL inhibition was greater in pretreatment patients than
controls. This sensitivity normalized after one week of therapy, but surprisingly
returned to pretreatment levels at week two. FACS analysis revealed increased AKT
pathway signaling after one week, followed by a decrease at week two. Platelet
counts correlated with the Bcl-xL /Bak ratio. Platelet survival may be enhanced
by TPO-R-agonists as a transient decrease in platelet sensitivity to apoptosis
was accompanied by transient activation of AKT. However, this mechanism has only
a short-lived effect. Megakaryocytes and platelets already present at the start
of TPO-R-agonist treatment appear to respond differently than those generated de
novo.
PMID- 25132653
TI - Childhood maltreatment and combat posttraumatic stress differentially predict
fear-related fronto-subcortical connectivity.
AB - BACKGROUND: Adult posttraumatic stress disorder (PTSD) has been characterized by
altered fear-network connectivity. Childhood trauma is a major risk factor for
adult PTSD, yet its contribution to fear-network connectivity in PTSD remains
unexplored. We examined, within a single model, the contribution of childhood
maltreatment, combat exposure, and combat-related posttraumatic stress symptoms
(PTSS) to resting-state connectivity (rs-FC) of the amygdala and hippocampus in
military veterans. METHODS: Medication-free male veterans (n = 27, average 26.6
years) with a range of PTSS completed resting-state fMRI. Measures including the
Clinician-Administered PTSD Scale (CAPS), Childhood Trauma Questionnaire (CTQ),
and Combat Exposure Scale (CES) were used to predict rs-FC using multilinear
regression. Fear-network seeds included the amygdala and hippocampus. RESULTS:
Amygdala: CTQ predicted lower connectivity to ventromedial prefrontal cortex
(vmPFC), but greater anticorrelation with dorsal/lateral PFC. CAPS positively
predicted connectivity to insula, and loss of anticorrelation with
dorsomedial/dorsolateral (dm/dl)PFC. Hippocampus: CTQ predicted lower
connectivity to vmPFC, but greater anticorrelation with dm/dlPFC. CES predicted
greater anticorrelation, whereas CAPS predicted less anticorrelation with dmPFC.
CONCLUSIONS: Childhood trauma, combat exposure, and PTSS differentially predict
fear-network rs-FC. Childhood maltreatment may weaken ventral prefrontal
subcortical circuitry important in automatic fear regulation, but, in a
compensatory manner, may also strengthen dorsal prefrontal-subcortical pathways
involved in more effortful emotion regulation. PTSD symptoms, in turn, appear to
emerge with the loss of connectivity in the latter pathway. These findings
suggest potential mechanisms by which developmental trauma exposure leads to
adult PTSD, and which brain mechanisms are associated with the emergence of PTSD
symptoms.
PMID- 25132655
TI - The heat-compression technique for the conversion of platelet-rich fibrin
preparation to a barrier membrane with a reduced rate of biodegradation.
AB - Platelet-rich fibrin (PRF) was developed as an advanced form of platelet-rich
plasma to eliminate xenofactors, such as bovine thrombin, and it is mainly used
as a source of growth factor for tissue regeneration. Furthermore, although a
minor application, PRF in a compressed membrane-like form has also been used as a
substitute for commercially available barrier membranes in guided-tissue
regeneration (GTR) treatment. However, the PRF membrane is resorbed within 2
weeks or less at implantation sites; therefore, it can barely maintain sufficient
space for bone regeneration. In this study, we developed and optimized a heat
compression technique and tested the feasibility of the resulting PRF membrane.
Freshly prepared human PRF was first compressed with dry gauze and subsequently
with a hot iron. Biodegradability was microscopically examined in vitro by
treatment with plasmin at 37 degrees C or in vivo by subcutaneous implantation in
nude mice. Compared with the control gauze-compressed PRF, the heat-compressed
PRF appeared plasmin-resistant and remained stable for longer than 10 days in
vitro. Additionally, in animal implantation studies, the heat-compressed PRF was
observed at least for 3 weeks postimplantation in vivo whereas the control PRF
was completely resorbed within 2 weeks. Therefore, these findings suggest that
the heat-compression technique reduces the rate of biodegradation of the PRF
membrane without sacrificing its biocompatibility and that the heat-compressed
PRF membrane easily could be prepared at chair-side and applied as a barrier
membrane in the GTR treatment.
PMID- 25132656
TI - Interobserver reproducibility and accuracy of p16/Ki-67 dual-stain cytology in
cervical cancer screening.
AB - BACKGROUND: Dual-stain cytology for p16 and Ki-67 has been proposed as a
biomarker in cervical cancer screening. The authors evaluated the reproducibility
and accuracy of dual-stain cytology among 10 newly trained evaluators. METHODS:
In total, 480 p16/Ki-67-stained slides from human papillomavirus-positive women
were evaluated in masked fashion by 10 evaluators. None of the evaluators had
previous experience with p16 or p16/Ki-67 cytology. All participants underwent
p16/Ki-67 training and subsequent proficiency testing. Reproducibility of dual
stain cytology was measured using the percentage agreement, individual and
aggregate kappa values, as well as McNemar statistics. Clinical performance for
the detection of cervical intraepithelial neoplasia grade 2 or greater (CIN2+)
was evaluated for each individual evaluator and for all evaluators combined
compared with the reference evaluation by a cytotechnologist who had extensive
experience with dual-stain cytology. RESULTS: The percentage agreement of
individual evaluators with the reference evaluation ranged from 83% to 91%, and
the kappa values ranged from 0.65 to 0.81. The combined kappa value was 0.71 for
all evaluators and 0.73 for cytotechnologists. The average sensitivity and
specificity for the detection of CIN2+ among novice evaluators was 82% and 64%,
respectively; whereas the reference evaluation had 84% sensitivity and 63%
specificity, respectively. Agreement on dual-stain positivity increased with
greater numbers of p16/Ki-67-positive cells on the slides. CONCLUSIONS: Good to
excellent reproducibility of p16/Ki-67 dual-stain cytology was observed with
almost identical clinical performance of novice evaluators compared with
reference evaluations. The current findings suggest that p16/Ki-67 dual-stain
evaluation can be implemented in routine cytology practice with limited training.
PMID- 25132658
TI - Cell culture media supplementation of uncommonly used sugars sucrose and tagatose
for the targeted shifting of protein glycosylation profiles of recombinant
protein therapeutics.
AB - Protein glycosylation is an important post-translational modification toward the
structure and function of recombinant therapeutics. The addition of
oligosaccharides to recombinant proteins has been shown to greatly influence the
overall physiochemical attributes of many proteins. It is for this reason that
protein glycosylation is monitored by the developer of a recombinant protein
therapeutic, and why protein glycosylation is typically considered a critical
quality attribute. In this work, we highlight a systematic study toward the
supplementation of sucrose and tagatose into cell culture media for the targeted
modulation of protein glycosylation profiles on recombinant proteins. Both sugars
were found to affect oligosaccharide maturation resulting in an increase in the
percentage of high mannose N-glycan species, as well as a concomitant reduction
in fucosylation. The latter effect was demonstrated to increase antibody
dependent cell-mediated cytotoxicity for a recombinant antibody. These
aforementioned results were found to be reproducible at different scales, and
across different Chinese hamster ovary cell lines. Through the selective
supplementation of these described sugars, the targeted modulation of protein
glycosylation profiles is demonstrated, as well as yet another tool in the cell
culture toolbox for ensuring product comparability.
PMID- 25132659
TI - Thyroid nodules with KRAS mutations are different from nodules with NRAS and HRAS
mutations with regard to cytopathologic and histopathologic outcome
characteristics.
AB - BACKGROUND: Mutations in the RAS gene in the thyroid gland result in the
activation of signaling pathways and are associated with a follicular growth
pattern and the probability of a carcinoma outcome ranging from 74% to 87%. In
the current study, the authors investigated the cytopathologic and
histopathologic features of common RAS mutation subtypes. METHODS: Malignant,
indeterminate, and selected benign thyroid cytology cases were tested
prospectively for the presence of NRAS61, HRAS61, and KRAS12/13 mutations. For
each case, the Bethesda System for thyroid cytopathology diagnosis, additional
cytologic descriptors, and surgical pathology outcomes were documented. The
Fisher exact test and Wilcoxon 2-sample test were used for statistical comparison
between the groups. RESULTS: A total of 204 thyroid fine-needle aspiration cases
with RAS mutations (93.6% of which were associated with indeterminate
cytopathology diagnoses) and corresponding surgical pathology resection specimens
were identified. The KRAS12/13 mutation was associated with a significantly lower
carcinoma outcome (41.7%) when compared with HRAS61 (95.5%) and NRAS61 (86.8%)
mutations (P<.0001). Furthermore, oncocytic change was observed in a
significantly higher percentage of cytology and resection specimens with
KRAS12/13 mutations (66.7% and 75.0%, respectively) in comparison with those with
HRAS61 (4.5% and 4.5%, respectively) and NRAS61 (15.4% and 14.7%, respectively)
mutations (P<.0001). RAS mutations also were identified in cases of poorly
differentiated carcinoma (NRAS61), anaplastic carcinoma (HRAS61), and medullary
thyroid carcinoma (HRAS61 and KRAS12/13). CONCLUSIONS: Subclassification of RAS
mutations in conjunction with cytopathologic evaluation improves presurgical risk
stratification, provides better insight into lesional characteristics, and may
influence patient management. In particular, KRAS12/13-mutated thyroid nodules
were found to be different from HRAS61-mutated and NRAS61-mutated nodules with
regard to cytopathologic and surgical outcome characteristics.
PMID- 25132657
TI - Decreased in vivo virulence and altered gene expression by a Brucella melitensis
light-sensing histidine kinase mutant.
AB - Brucella species utilize diverse virulence factors. Previously, Brucella abortus
light-sensing histidine kinase was identified as important for cellular
infection. Here, we demonstrate that a Brucella melitensis LOV-HK (BM-LOV-HK)
mutant strain has strikingly different gene expression than wild type. General
stress response genes including the alternative sigma factor rpoE1 and its anti
anti-sigma factor phyR were downregulated, while flagellar, quorum sensing (QS),
and type IV secretion system genes were upregulated in the DeltaBM-LOV-HK strain
vs. wild type. Contextually, expression results agree with other studies of
transcriptional regulators involving DeltarpoE1, DeltaphyR, DeltavjbR, and
DeltablxR (DeltababR) Brucella strains. Additionally, deletion of BM-LOV-HK
decreases virulence in mice. During C57BL/6 mouse infection, the DeltaBM-LOV-HK
strain had 2 logs less CFUs in the spleen 3 days postinfection, but similar
levels 6 days post infection compared to wild type. Infection of IRF-1(-/-) mice
more specifically define DeltaBM-LOV-HK strain attenuation with fewer bacteria in
spleens and significantly increased survival of mutant vs. wild-type infected IRF
1(-/-) mice. Upregulation of flagella, QS, and VirB genes, along with
downregulation of rpoE1 and related sigma factor, rpoH2 (BMEI0280) suggest that
BM-LOV-HK modulates both QS and general stress response regulatory components to
control Brucella gene expression on a global level.
PMID- 25132660
TI - Interactions between patients, providers, and health systems and technical
quality of care.
AB - OBJECTIVE: Prior studies have established disparities by race/ethnicity and
socioeconomic status (SES) in the kind, quantity, and technical quality of
systemic lupus erythematosus (SLE) care and outcomes. In this study we evaluate
whether disparities exist in assessments of interactions with health care
providers and health plans and whether such interactions affect the technical
quality of SLE care. METHODS: Data derive from the Lupus Outcomes Study (LOS).
Principal data collection is an annual structured phone interview including items
from the Consumer Assessment of Health Plans and Interpersonal Processes of Care
Scale measuring dimensions of health care interactions. We use general estimating
equations to assess whether disparities exist by race/ethnicity and SES in being
in the lowest quartile of ratings of such interactions and whether ratings in the
lowest quartile of interactions are associated with technical quality of care
after adjustment for sociodemographic and disease characteristics. RESULTS: In
the 2012 LOS interview, there were 793 respondents, of whom 640 had >=1 visit to
their principal SLE provider. Nonwhite race/ethnicity and education were not
associated with low ratings on any dimension of provider or system interaction;
poverty was associated only with low ratings of health plan interactions. After
adjustment for demographics, SLE status, and health care variables, ratings in
the lowest quartile on all dimensions were associated with significantly lower
technical quality of care. CONCLUSION: Ratings in the lowest quartile on all
dimensions of interactions with providers and the health care system were
associated with lower technical quality of care, potentially resulting in poorer
SLE outcomes.
PMID- 25132661
TI - Integration of medical imaging including ultrasound into a new clinical anatomy
curriculum.
AB - In 2008 a new clinical anatomy curriculum with integrated medical imaging
component was introduced into the University of Sydney Medical Program. Medical
imaging used for teaching the new curriculum included normal radiography, MRI, CT
scans, and ultrasound imaging. These techniques were incorporated into teaching
over the first two years of the program as a part of anatomy practical sessions,
in addition to dedicated lectures and tutorials given by imaging specialists.
Surveys were conducted between 2009 and 2012 to evaluate the student acceptance
of the integration. Students were asked to rate individual activities as well as
provide open-ended comments. The number of students who responded to the surveys
varied from 40% to 98%. Over 90% of the respondents were satisfied with the
overall quality of teaching in the anatomy units. In summary, 48% to 63% of the
responding students thought that the specialist imaging lectures helped them
learn effectively; 72% to 77% of students thought that the cross-sectional
practical sessions helped them to better understand the imaging modalities of CT,
MRI, and ultrasound; 76% to 80% of students considered hands-on ultrasound
session to be useful in understanding the application of ultrasound in abdominal
imaging. The results also revealed key similarities and differences in student
perceptions of the new integrated curriculum for students with both a high and
low prior exposure to anatomy. Further evaluation will aid in refining the
integrated medical imaging program and providing its future direction.
PMID- 25132663
TI - Incidence of giant cell arteritis and characteristics of patients: data-driven
analysis of comorbidities.
AB - OBJECTIVE: To establish the incidence of giant cell arteritis (GCA), cumulative
use of prednisolone, and comorbidities most associated with GCA. METHODS: The
data source was the UK Clinical Practice Research Datalink. Selection criteria
included >=1 record of a diagnostic term for GCA between January 1, 2000 and
December 31, 2011, age >=50 years, and >=1 prescription of oral or systemic
corticosteroid. Controls were selected randomly (2:1), with year of birth,
practice, and followup duration (<2 or >=2 years) as matching variables. Analysis
was data driven; all comorbidities were identified in a 2-year window, with
relative risk (RR) calculated and rank ordered. RESULTS: A total of 4,671
patients fulfilled the definition of GCA (incidence, 1.0 per 10,000 person
years), with highest incidence (7.4 per 10,000 person-years) in women ages 70-79
years. Of the 4,671 patients, 4,655 (99.7%) were prescribed prednisolone. In the
group with >=2 years' followup (n = 3,074), the mean number of prednisolone
prescriptions was 32.1, and the mean cumulative dose was 8,640 mg; 1,034 patients
(33.4%) received a cumulative dose of >=10,000 mg. Comorbidities strongly
associated with GCA were polymyalgia rheumatica (RR 14.9, 95% confidence interval
[95% CI] 11.9-18.7), visual disturbances (RR 4.6, 95% CI 2.7-7.8), facial pain
(RR 3.3, 95% CI 2.1-5.3), osteoporosis (RR 2.9, 95% 2.3-3.7), hypokalemia (RR
2.5, 95% CI 1.6-3.9), and various infections such as oral/esophageal thrush (RR
3.7, 95% CI 2.2-6.0) and herpes zoster (RR 2.6, 95% CI 1.6-4.1). CONCLUSION: GCA
is relatively uncommon; its incidence peaks at age 70-79 years in women. Overall,
GCA patients in the UK are treated with high cumulative prednisolone doses. Many
conditions are associated with GCA, including several related to corticosteroid
use.
PMID- 25132664
TI - Integration of gross anatomy in an organ system-based medical curriculum:
strategies and challenges.
AB - The University of Alabama School of Medicine (UASOM) instituted a fully
integrated, organ system-based preclinical curriculum in 2007. Gross anatomy and
embryology were integrated with other basic science disciplines throughout the
first two years of undergraduate medical education. Here we describe the methods
of instruction and integration of gross anatomy and embryology in this curriculum
as well as challenges faced along the way. Gross anatomy and embryology are
taught through a combination of didactic lectures, team-based learning
activities, and cadaveric dissection laboratories. Vertical integration occurs
through third- and fourth-year anatomy and embryology elective courses. Radiology
is integrated with anatomy instruction through self-study modules and hands-on
ultrasound sessions. Our model of anatomy instruction is time efficient,
clinically relevant, and effective as demonstrated by student performance on the
United States Medical Licensing Examination((r)) (USMLE((r)) ) Step 1
examination. We recommend that medical schools considering full integration of
gross anatomy and embryology (1) carefully consider the sequencing of organ
system modules, (2) be willing to sacrifice anatomical detail for clinical
application, (3) provide additional electives to third- and fourth-year students,
and (4) integrate radiology with anatomical education.
PMID- 25132662
TI - Using surgical appropriateness criteria to examine outcomes of total knee
arthroplasty in a United States sample.
AB - OBJECTIVE: We determined outcomes for patients classified as appropriate,
inconclusive, or inappropriate for total knee arthroplasty (TKA) using a modified
version of a validated appropriateness algorithm. Outcome measurement was
conceptualized as short-term postoperative change attributable primarily to
surgery and rehabilitation (2 months) and as longer-term postoperative change and
recovery (1 and 2 years). METHODS: Preoperative and yearly postoperative Western
Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function, Knee
Injury and Osteoarthritis Outcome Score (KOOS) symptoms and KOOS pain scores were
examined for persons undergoing primary TKA in the Osteoarthritis Initiative.
Multigroup, 2-piece latent growth curve modeling was used to determine
differences in outcome variable changes for each group from presurgery to 2
months postsurgery, as well as over a 2-year postoperative period. RESULTS: Data
from 167 persons with primary TKA were examined. Prevalence rates of appropriate,
inconclusive, and inappropriate judgments were 47.9%, 20.8%, and 31.3%,
respectively. The inappropriate group showed no change at 2 months following
surgery, while appropriate and inconclusive groups had substantial improvement in
all outcomes. One-year and 2-year postoperative recovery outcomes were not
significantly different among the 3 groups. CONCLUSION: The inappropriate group
was unchanged 2 months after surgery and on average improved by 2.3 WOMAC
function points from presurgery to 1 year following surgery based on our models.
Appropriate and inconclusive groups improved by an average of 19.8 WOMAC function
points at 1-year postsurgery. These data provide a compelling case for consensus
building efforts to define eligibility criteria for TKA with the goals of
reducing variation in patient selection and optimizing both change over time and
final outcomes.
PMID- 25132665
TI - Highly active macromolecular prodrugs inhibit expression of the hepatitis C virus
genome in the host cells.
AB - Efficacious, potent, and at the same time nontoxic macromolecular prodrugs of
ribavirin are designed taking advantage over prodrug activation by the
intracellular milieu. Activity of these prodrugs is illustrated in the cells
hosting hepatitis C virus replication and also in the cells implicated in the
inflammatory response to the viral infection.
PMID- 25132666
TI - Cross-sectional evidence for a decrease in cognitive function with age in
children with autism spectrum disorders?
AB - Autism spectrum disorders (ASD) are associated with early disturbances in brain
maturation processes and these interferences presumably have their consequences
for the progressive emergence of cognitive deficits later in life, as expressed
in intelligence profiles. In this study, we addressed the impact of age on
cognitive functioning of 6- to 15-year-old children and adolescents with ASD.
Intelligence profiles were measured by the Wechsler Intelligence Scale for
Children and compared among four consecutive age cohorts (children aged 6.17-8.03
years, 8.04-9.61 years, and 9.68-11.50 years and adolescents aged 11.54-15.85
years) of 237 high-functioning boys with ASD. The results clearly demonstrated
that the global intelligence level was lower in children aged 8 years and older,
when compared with 6- and 7-year-old children with ASD. This is mostly due to the
Freedom From Distractibility factor, suggesting that older children were less
able to sustain their attention, they were more distractible, or had more graph
motor difficulties. Moreover, an effect of age was also found with respect to the
relatively poor performance on the subtest Comprehension when compared with other
verbal comprehension subtests, indicating that specifically the impairments in
verbal comprehension and social reasoning abilities were more profound in older
children when compared with 6- and 7-year-old children with ASD. Findings of this
cross-sectional study showed that it is relevant to take age into account when
evaluating the impact of cognitive impairments on intelligence in children with
ASD, because the impact of these developmental disorders might be different at
different ages.
PMID- 25132669
TI - Is the modified disease activity score superior to the disease activity score in
early arthritis and rheumatoid arthritis? Comment on the article by Baker et al.
PMID- 25132667
TI - Disease mechanisms in rheumatology--tools and pathways: defining functional
genetic variants in autoimmune diseases.
PMID- 25132670
TI - The use of dried blood spots for quantification of 15 antipsychotics and 7
metabolites with ultra-high performance liquid chromatography - tandem mass
spectrometry.
AB - Therapeutic drug monitoring of antipsychotics is important in optimizing
individual therapy. In psychiatric populations, classical venous blood sampling
is experienced as frightening. Interest in alternative techniques, like dried
blood spots (DBS), has consequently increased. A fast and easy to perform DBS
method for quantification of 16 antipsychotics (amisulpride, aripiprazole,
asenapine, bromperidol, clozapine, haloperidol, iloperidone, levosulpiride,
lurasidone, olanzapine, paliperidone, pipamperone, quetiapine, risperidone,
sertindole and zuclopenthixol) and 8 metabolites was developed. DBS were prepared
using 25 MUL of whole blood and extraction of complete spots was performed using
methanol: methyl-t-butyl-ether (4:1). After evaporation, the extract was
reconstituted in the mobile phase and 10 MUL were injected on an ultra-high
performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).
Separation using a C18 column and gradient elution with a flow rate of 0.5 mL/min
resulted in a 6-min run-time. Ionization was performed in positive mode and a
dynamic MRM method was applied. Median recovery was 66.4 % (range 28.7-84.5%).
Accuracy was within the acceptance criteria, except for pipamperone (LLOQ and low
concentration) and lurasidone (low concentration). Imprecision was only aberrant
for lurasidone at low and medium concentration. All compounds were stable during
1 month at room temperature, 4 degrees C and -18 degrees C. Lurasidone was
unstable when the extract was stored for 12 h on the autosampler. Absolute matrix
effects (ME) (median 66.1%) were compensated by the use of deuterated IS (median
98.8%). The DBS method was successfully applied on 25-MUL capillary DBS from
patients and proved to be a reliable alternative for quantification of all
antipsychotics except for olanzapine and N-desmethylolanzapine.
PMID- 25132671
TI - Development of an autoimmune syndrome affecting the skin and internal organs in P
selectin glycoprotein ligand 1 leukocyte receptor-deficient mice.
AB - OBJECTIVE: To define and characterize the progression of the spontaneous
autoimmune disease that develops in mice in the absence of the leukocyte adhesion
receptor P-selectin glycoprotein ligand 1 (PSGL-1). METHODS: Skin-resident immune
cells from PSGL-1-deficient mice and C57BL/6 control mice of different ages were
isolated and analyzed by flow cytometry. Biochemical parameters were analyzed in
mouse serum and urine, and the presence of serum autoantibodies was investigated.
Skin and internal organs were extracted, and their structure was analyzed
histologically. RESULTS: Skin-resident innate and adaptive immune cells from PSGL
1(-/-) mice had a proinflammatory phenotype with an imbalanced T effector
cell:Treg cell ratio. Sera from PSGL-1(-/-) mice had circulating autoantibodies
commonly detected in connective tissue-related human autoimmune diseases.
Biochemical and histologic analysis of skin and internal organs revealed skin
fibrosis and structural and functional abnormalities in the lungs and kidneys.
Furthermore, PSGL-1(-/-) mice exhibited vascular alterations, showing loss of
dermal vessels, small vessel medial layer remodeling in the lungs and kidneys,
and ischemic processes in the kidney that promote renal infarcts. CONCLUSION: Our
study demonstrates that immune system overactivation due to PSGL-1 deficiency
triggers an autoimmune syndrome with characteristics similar to systemic
sclerosis, including skin fibrosis, vascular alterations, and systemic organ
involvement. These results suggest that PSGL-1 expression contributes to the
maintenance of the homeostasis of the immune system and could act as a barrier
for autoimmunity in mice.
PMID- 25132673
TI - Reply: To PMID 24757132.
PMID- 25132674
TI - Micro-scale blood particulate dynamics using a non-uniform rational B-spline
based isogeometric analysis.
AB - The current research presents a novel method in which blood particulates -
biconcave red blood cells (RBCs) and spherical cells are modeled using
isogeometric analysis, specifically Non-Uniform Rational B-Splines (NURBS) in 3
D. The use of NURBS ensures that even with a coarse representation, the geometry
of the blood particulates maintains an accurate description when subjected to
large deformations. The fundamental advantage of this method is the coupling of
the geometrical description and the stress analysis of the cell membrane into a
single, unified framework. Details on the modeling approach, implementation of
boundary conditions and the membrane mechanics analysis using isogeometric
modeling are presented, along with validation cases for spherical and biconcave
cells. Using NURBS - based isogeometric analysis, the behavior of individual
cells in fluid flow is presented and analyzed in different flow regimes using as
few as 176 elements for a spherical cell and 220 elements for a biconcave RBC.
This work provides a framework for modeling a large number of 3-D deformable
biological cells, each with its own geometric description and membrane
properties. To the best knowledge of the authors, this is the first application
of the NURBS - based isogeometric analysis to model and simulate blood
particulates in flow in 3D.
PMID- 25132672
TI - Endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 1
targets misfolded HLA-B27 dimers for endoplasmic reticulum-associated
degradation.
AB - OBJECTIVE: HLA-B27 forms misfolded heavy chain dimers, which may predispose
individuals to inflammatory arthritis by inducing endoplasmic reticulum (ER)
stress and the unfolded protein response (UPR). This study was undertaken to
define the role of the UPR-induced ER-associated degradation (ERAD) pathway in
the disposal of HLA-B27 dimeric conformers. METHODS: HeLa cell lines expressing
only 2 copies of a carboxy-terminally Sv5-tagged HLA-B27 were generated. The ER
stress-induced protein ER degradation-enhancing alpha-mannosidase-like protein 1
(EDEM1) was overexpressed by transfection, and dimer levels were monitored by
immunoblotting. EDEM1, the UPR-associated transcription factor X-box binding
protein 1 (XBP-1), the E3 ubiquitin ligase hydroxymethylglutaryl-coenzyme A
reductase degradation 1 (HRD1), and the degradation-associated proteins derlin 1
and derlin 2 were inhibited using either short hairpin RNA or dominant-negative
mutants. The UPR-associated ERAD of HLA-B27 was confirmed using ER stress
inducing pharamacologic agents in kinetic and pulse chase assays. RESULTS: We
demonstrated that UPR-induced machinery can target HLA-B27 dimers and that dimer
formation can be controlled by alterations to expression levels of components of
the UPR-induced ERAD pathway. HLA-B27 dimers and misfolded major
histocompatibility complex class I monomeric molecules bound to EDEM1 were
detected, and overexpression of EDEM1 led to inhibition of HLA-B27 dimer
formation. EDEM1 inhibition resulted in up-regulation of HLA-B27 dimers, while
UPR-induced ERAD of dimers was prevented in the absence of EDEM1. HLA-B27 dimer
formation was also enhanced in the absence of XBP-1, HRD1, and derlins 1 and 2.
CONCLUSION: The present findings indicate that the UPR ERAD pathway can dispose
of HLA-B27 dimers, thus presenting a potential novel therapeutic target for
modulation of HLA-B27-associated inflammatory disease.
PMID- 25132675
TI - Fibromyalgia syndrome and small-fiber neuropathy: comment on the article by Caro
and Winter.
PMID- 25132676
TI - Impact of complex blast waves on the human head: a computational study.
AB - Head injuries due to complex blasts are not well examined because of limited
published articles on the subject. Previous studies have analyzed head injuries
due to impact from a single planar blast wave. Complex or concomitant blasts
refer to impacts usually caused by more than a single blast source, whereby the
blast waves may impact the head simultaneously or consecutively, depending on the
locations and distances of the blast sources from the subject, their blast
intensities, the sequence of detonations, as well as the effect of blast wave
reflections from rigid walls. It is expected that such scenarios will result in
more serious head injuries as compared to impact from a single blast wave due to
the larger effective duration of the blast. In this paper, the utilization of a
head-helmet model for blast impact analyses in Abaqus(TM) (Dassault Systemes,
Singapore) is demonstrated. The model is validated against studies published in
the literature. Results show that the skull is capable of transmitting the blast
impact to cause high intracranial pressures (ICPs). In addition, the pressure
wave from a frontal blast may enter through the sides of the helmet and wrap
around the head to result in a second impact at the rear. This study recommended
better protection at the sides and rear of the helmet through the use of foam
pads so as to reduce wave entry into the helmet. The consecutive frontal blasts
scenario resulted in higher ICPs compared with impact from a single frontal
blast. This implied that blast impingement from an immediate subsequent pressure
wave would increase severity of brain injury. For the unhelmeted head case, a
peak ICP of 330 kPa is registered at the parietal lobe which exceeds the 235 kPa
threshold for serious head injuries. The concurrent front and side blasts
scenario yielded lower ICPs and skull stresses than the consecutive frontal
blasts case. It is also revealed that the additional side blast would only
significantly affect ICPs at the temporal and parietal lobes when compared with
results from the single frontal blast case. By analyzing the pressure wave flow
surrounding the head and correlating them with the consequential evolution of ICP
and skull stress, the paper provides insights into the interaction mechanics
between the concomitant blast waves and the biological head model.
PMID- 25132677
TI - Reply: To PMID 24719395.
PMID- 25132678
TI - Chronic rhinosinusitis patients have decreased lung function.
AB - BACKGROUND: The relationship between upper and lower airway diseases has been
reported. However, the pulmonary function of patients with chronic rhinosinusitis
(CRS) has not been fully examined. METHODS: Pulmonary function was measured in
273 patients with CRS and 100 age-matched normal control subjects. No patients
with chronic obstructive pulmonary disease (COPD) were included in this study.
The patients with CRS were divided into 8 subgroups based on the presence of
asthma, sensitization to common inhaled antigens, and nasal polyposis. The
relationships between pulmonary function and clinical parameters, including
radiographic severity of CRS according to the Lund-Mackay computed tomography
(CT) staging system, eosinophil count in the peripheral blood, and serum total
immunoglobulin E (IgE) levels, were assessed. RESULTS: In pulmonary function
testing, the CRS patients had affected pulmonary function. The CRS patients
without asthma showed latent obstructive pulmonary function changes when compared
to normal controls. No significant correlations were observed between pulmonary
function and any clinical parameters (Lund-Mackay CT staging score, eosinophil
count in the peripheral blood, and serum total IgE levels). CONCLUSION: CRS
patients had significant obstructive lung function changes regardless of the
presence of asthma. The patients with CRS who had not been clinically diagnosed
as having lower respiratory tract diseases might have had subclinical lower
airway diseases. Therefore, clinicians should be aware of pulmonary function and
lower lung diseases in patients with CRS.
PMID- 25132679
TI - Regulation of cytokine polarization and T cell recruitment to inflamed paws in
mouse collagen-induced arthritis by the chemokine receptor CXCR6.
AB - OBJECTIVE: The chemokine receptor CXCR6 is highly expressed on lymphocytes
isolated from the synovium of patients with rheumatoid arthritis, psoriatic
arthritis, or juvenile idiopathic arthritis, suggesting that CXCR6 regulates
immune cell activation or infiltration into arthritic joints. This study was
undertaken to examine the role of CXCR6 in T cell activation and arthritis
development. METHODS: A collagen-induced arthritis model was used to examine
arthritis development in wild-type and CXCR6(-/-) mice. CXCR6 expression,
lymphocyte accumulation, and intracellular cytokine production were examined by
flow cytometry. Collagen-specific antibodies were measured in the serum. Collagen
specific recall responses were examined in vitro via proliferation and cytokine
release assays. T cell homing to inflamed joints was examined using competitive
adoptive transfer of dye-labeled lymphocytes from wild-type and CXCR6(-/-) mice.
RESULTS: The numbers of CXCR6+ T cells were increased in the paws and draining
lymph nodes of arthritic mice. The incidence of arthritis, disease severity,
extent of T cell accumulation, and levels of collagen-specific IgG2a antibodies
were significantly reduced in CXCR6(-/-) mice compared to wild-type mice. T cells
from wild-type mice exhibited Th1 (interferon-gamma [IFNgamma]) polarization in
the inguinal lymph nodes following immunization. At disease peak, this shifted to
a Th17 (interleukin-17A [IL-17A]) response in the popliteal lymph nodes. T cells
in CXCR6(-/-) mice exhibited impaired cytokine polarization, resulting in a
decreased frequency and number of IL-17A- and IFNgamma-producing cells.
Recruitment of activated CXCR6(-/-) mouse T cells to the inflamed paws was
impaired compared to recruitment of wild-type mouse T cells. CONCLUSION: These
experiments demonstrate that CXCR6 plays important roles in the pathogenesis of
arthritis through its effects on both T cell cytokine polarization and homing of
T cells to inflamed joints.
PMID- 25132680
TI - How does pharmacogenetic testing alter the treatment course and patient response
for chronic-pain patients in comparison with the current "trial-and-error"
standard of care?
AB - PURPOSE: To evaluate if pharmacogenetic testing (PT) holds value for pain
management practitioners by identifying the potential applications of
pharmacogenetic research as well as applications in practice. DATA SOURCES: A
review of the literature was conducted utilizing the databases EBSCOhost,
Biomedical Reference Collection, CINAHL, Health Business: Full Text, Health
Source: Nursing/Academic Edition, and MEDLINE with the keywords, personalized
medicine, cytochrome P450, and phamacogenetics. CONCLUSIONS: Chronic-pain
patients present some of the most challenging patients to manage medically. Often
paired with persistent, life-altering pain, they might also have oncologic and
psychological comorbidities that can further complicate their management. One
step in-office PT is now widely available to optimize management of complicated
patients and affectively remove the "trial-and-error" process of medication
therapy. IMPLICATIONS FOR PRACTICE: Practitioners must be familiar with the
genetic determinants that affect a patient's response to medications in order to
decrease preventable morbidity and mortality associated with drug-drug and
patient-drug interactions, and to provide cost-effective care through avoidance
of inappropriate medications. Improved pain managements will impove patient
outcomes and satisfaction.
PMID- 25132682
TI - Collaborative arrangements for Australian nurse practitioners: a policy analysis.
AB - PURPOSE: In Australia in 2010, nurse practitioners (NPs) were granted legislated
access to the Medical Benefits Scheme (MBS) and Pharmaceutical Benefits Scheme
(PBS) as providers. These schemes are the federal schemes for third-party
reimbursement for health care and medications. As a condition of access to the
schemes, it was determined that collaborative arrangements needed to be in place
as part of eligibility criteria for NPs. This article is the first published
policy analysis of this determination. DATA SOURCES: Published literature and
available grey literature (including meeting minutes), and media content, was
accessed and analyzed. CONCLUSIONS: The policy that was the National Health
Collaborative arrangements for Nurse Practitioners Determination to amend the
Australian National Health Act 1953 was a success. The policy led to NP access as
providers to the MBS and PBS in Australia. IMPLICATIONS FOR PRACTICE:
Understanding the policy process as it relates to the determination of the need
for collaborative arrangements demystifies the process and origins of the policy
for NPs in Australia. Understanding the determination means NPs in Australia will
not artificially reduce scope of practice based on recommendations from the
medical lobby. Clear research direction is provided that may inform the next
policy cycle.
PMID- 25132681
TI - Serum phytanic and pristanic acid levels and prostate cancer risk in Finnish
smokers.
AB - Phytanic acid is a saturated branched-chain fatty acid found predominantly in red
meat and dairy products, and may contribute to the elevated risks of prostate
cancer associated with higher consumption of these foods. Pristanic acid is
formed during peroxisomal oxidation of phytanic acid, and is the direct substrate
of alpha-Methyl-CoA-Racemase (AMACR)--an enzyme that is consistently
overexpressed in prostate tumors relative to benign tissue. We measured phytanic
and pristanic acids as percentages of total fatty acids by gas chromatography
mass spectrometry in prediagnostic blood samples from 300 prostate cancer cases
and 300 matched controls, all of whom were participants in the Alpha-Tocopherol,
Beta-Carotene Cancer Prevention (ATBC) Study supplementation trial and follow-up
cohort. In addition to providing a fasting blood sample at baseline, all men
completed extensive diet, lifestyle, and medical history questionnaires. Among
controls, the strongest dietary correlates of serum phytanic and pristanic acids
were saturated fat, dairy fat, and butter (r = 0.50 and 0.40, 0.46 and 0.38, and
0.40 and 0.37, respectively; all P-values <0.001). There was no association
between serum phytanic acid and risk of total or aggressive prostate cancer in
multivariate logistic regression models (for increasing quartiles, odds ratios
(OR) and 95% confidence intervals (CI) for aggressive cancer were 1.0 (referent),
1.62 (0.97-2.68), 1.12 (0.66-1.90), and 1.14 (0.67-1.94), P(trend) = 0.87).
Pristanic acid was strongly correlated with phytanic acid levels (r = 0.73, P <
0.0001), and was similarly unrelated to prostate cancer risk. Significant
interactions between phytanic and pristanic acids and baseline circulating beta
carotene concentrations were noted in relation to total and aggressive disease
among participants who did not receive beta-carotene supplements as part of the
original ATBC intervention trial. In summary, we observed no overall association
between serum phytanic and pristanic acid levels and prostate cancer risk.
Findings indicating that the direction and magnitude of these associations
depended upon serum levels of the antioxidant beta-carotene among men not taking
beta-carotene supplements should be interpreted cautiously, as they are likely
due to chance.
PMID- 25132684
TI - Ultrasound-guided fine-needle aspiration of a posterior neck dedifferentiated
liposarcoma with MDM2 fluorescence in situ hybridization performed on a Pap
stained smear.
AB - Head and neck liposarcomas, while rare, tend to be subcutaneous and well
differentiated. Dedifferentiated liposarcomas of the head and neck are
exceedingly rare in the literature. We present a case of a dedifferentiated
liposarcoma arising in the soft tissue of the posterior neck of an 86-year-old
man and diagnosed by fine-needle aspiration. Aspirate smears showed a dual
population of atypical lipomatous and spindled cells. MDM2 (murine double minute
2) amplification was demonstrated on a Pap-stained smear using fluorescence in
situ hybridization (FISH). To the best of our knowledge, this is the first report
of MDM2 FISH amplification in a liposarcoma performed on an aspirate smear.
PMID- 25132683
TI - Suppression of Aggrus/podoplanin-induced platelet aggregation and pulmonary
metastasis by a single-chain antibody variable region fragment.
AB - Almost all highly metastatic tumor cells possess high platelet aggregating
abilities, thereby form large tumor cell-platelet aggregates in the
microvasculature. Embolization of tumor cells in the microvasculature is
considered to be the first step in metastasis to distant organs. We previously
identified the platelet aggregation-inducing factor expressed on the surfaces of
highly metastatic tumor cells and named as Aggrus. Aggrus was observed to be
identical to the marker protein podoplanin (alternative names, T1alpha, OTS-8,
and others). Aggrus is frequently overexpressed in several types of tumors and
enhances platelet aggregation by interacting with the platelet receptor C-type
lectin-like receptor 2 (CLEC-2). Here, we generated a novel single-chain antibody
variable region fragment (scFv) by linking the variable regions of heavy and
light chains of the neutralizing anti-human Aggrus monoclonal antibody MS-1 with
a flexible peptide linker. Unfortunately, the generated KM10 scFv failed to
suppress Aggrus-induced platelet aggregation in vitro. Therefore, we performed
phage display screening and finally obtained a high-affinity scFv, K-11. K-11
scFv was able to suppress Aggrus-induced platelet aggregation in vitro. Moreover,
K-11 scFv prevented the formation of pulmonary metastasis in vivo. These results
suggest that K-11 scFv may be useful as metastasis inhibitory scFv and is
expected to aid in the development of preclinical and clinical examinations of
Aggrus-targeted cancer therapies.
PMID- 25132685
TI - Catalytic Activity of Ultrathin Pt Films on Aligned Carbon Nanotube Arrays.
AB - Uniform ultrathin Pt films were electrodeposited onto an aligned array of carbon
nanotubes (CNTs) for high-area chemically stable methanol fuel cell anodes.
Electrochemical treatment of the graphitic CNT surfaces by diazoniumbenzoic acid
allowed for uniform Pt electroplating. The mass activity of the Pt thin film can
reach 400 A/g at a scan rate of 20 mV/s and in a solution of 1 M CH3OH/0.5 M
H2SO4. A programmed pulse potential at 0V was also seen to nearly eliminate the
effects of carbon monoxide poisoning. The mass activity of Pt for methanol
oxidation can be maintained at 300 A/g for more than 3000 s, which is 19 times of
that under a constant potential of 0.7 V (vs Ag/AgCl).
PMID- 25132686
TI - The Role of Distal Variables in Behavior Change: Effects of Adolescents' Risk for
Marijuana Use on Intention to Use Marijuana.
AB - This study uses an integrative model of behavioral prediction as an account of
adolescents' intention to use marijuana regularly. Adolescents' risk for using
marijuana regularly is examined to test the theoretical assumption that distal
variables affect intention indirectly. Risk affects intention indirectly if low
risk and high-risk adolescents differ on the strength with which beliefs about
marijuana are held, or if they differ on the relative importance of predictors of
intention. A model test confirmed that the effect of risk on intention is
primarily indirect. Adolescents at low and high risk particularly differed in
beliefs concerning social costs and costs to self-esteem. Not surprisingly, at
risk adolescents took a far more positive stand toward using marijuana regularly
than did low-risk adolescents. On a practical level, the integrative model proved
to be an effective tool for predicting intention to use marijuana, identifying
key variables for interventions, and discriminating between target populations in
terms of determinants of marijuana use.
PMID- 25132687
TI - Dual Studies on a Hydrogen-Deuterium Exchange of Resorcinol and the Subsequent
Kinetic Isotope Effect.
AB - An efficient laboratory experiment has been developed for undergraduate students
to conduct hydrogen-deuterium (H-D) exchange of resorcinol by electrophilic
aromatic substitution using D2O and a catalytic amount of H2SO4. The resulting
labeled product is characterized by 1H NMR. Students also visualize a significant
kinetic isotope effect (kH/kD ~ 3 to 4) by adding iodine tincture to solutions of
unlabeled resorcinol and the H-D exchange product. This method is highly
adaptable to fit a target audience and has been successfully implemented in a
pedagogical capacity with second-year introductory organic chemistry students as
part of their laboratory curriculum. It was also adapted for students at the
advanced high school level.
PMID- 25132688
TI - Modeling Oral Reading Fluency Development in Latino Students: A Longitudinal
Study Across Second and Third Grade.
AB - This study examines growth in oral reading fluency across 2nd and 3rd grade for
Latino students grouped in 3 English proficiency levels: students receiving
English as a second language (ESL) services (n = 2,182), students exited from ESL
services (n = 965), and students never designated as needing services (n =
1,857). An important focus was to learn whether, within these 3 groups,
proficiency levels and growth were reliably related to special education status.
Using hierarchical linear modeling, the authors compared proficiency levels and
growth in oral reading fluency in English between and within groups and then to
state reading benchmarks. Findings indicate that oral reading fluency scores
reliably distinguished between students with learning disabilities and typically
developing students within each group (effect sizes ranging from 0.96 to 1.51).
The growth trajectory included a significant quadratic trend (generally slowing
over time). These findings support the effectiveness of using oral reading
fluency in English to screen and monitor reading progress under Response to
Intervention models, but also suggest caution in interpreting oral reading
fluency data as part of the process in identifying students with learning
disabilities.
PMID- 25132689
TI - Canalization of body size matters for lifetime reproductive success of male
predatory mites (Acari: Phytoseiidae).
AB - The adaptive canalization hypothesis predicts that highly fitness-relevant traits
are canalized via past selection, resulting in low phenotypic plasticity and high
robustness to environmental stress. Accordingly, we hypothesized that the level
of phenotypic plasticity of male body size of the predatory mites Phytoseiulus
persimilis (low plasticity) and Neoseiulus californicus (high plasticity)
reflects the effects of body size variation on fitness, especially male lifetime
reproductive success (LRS). We first generated small and standard-sized males of
P. persimilis and N. californicus by rearing them to adulthood under limited and
ample prey supply, respectively. Then, adult small and standard-sized males were
provided with surplus virgin females throughout life to assess their mating and
reproductive traits. Small male body size did not affect male longevity or the
number of fertilized females but reduced male LRS of P. persimilis but not N.
californicus. Proximately, the lower LRS of small than standard-sized P.
persimilis males correlated with shorter mating durations, probably decreasing
the amount of transferred sperm. Ultimately, we suggest that male body size is
more strongly canalized in P. persimilis than N. californicus because deviation
from standard body size has larger detrimental fitness effects in P. persimilis
than N. californicus.
PMID- 25132690
TI - Variable Selection in Generalized Functional Linear Models.
AB - Modern research data, where a large number of functional predictors is collected
on few subjects are becoming increasingly common. In this paper we propose a
variable selection technique, when the predictors are functional and the response
is scalar. Our approach is based on adopting a generalized functional linear
model framework and using a penalized likelihood method that simultaneously
controls the sparsity of the model and the smoothness of the corresponding
coefficient functions by adequate penalization. The methodology is characterized
by high predictive accuracy, and yields interpretable models, while retaining
computational efficiency. The proposed method is investigated numerically in
finite samples, and applied to a diffusion tensor imaging tractography data set
and a chemometric data set.
PMID- 25132691
TI - Multidimensional Screening and Methodology Development for Condensations
Involving Complex 1,2-Diketones.
AB - Multidimensional reaction screening employing complex 1,2-cycloheptanediones is
described. The studies have enabled the discovery of regioselective, Lewis acid
mediated condensations with substituted ureas and a diastereoselective
hydrogenation process which proceeds via an interesting allylpalladium hydride
isomerization.
PMID- 25132692
TI - Alkylphenols in Surface Sediments of the Gulf of Gdansk (Baltic Sea).
AB - The widespread use of alkylphenols in European industry has led to their presence
in the environment and the living organisms of the Baltic Sea. The present study
(2011-2012) was designed to determine the concentrations of alkylphenols, 4
nonylphenol (NP) and 4-tert-octylphenol (OP), in surface sediments of the Gulf of
Gdansk, a section of the Baltic that lies in close proximity to industrial and
agricultural areas and borders with an agglomeration of nearly one million
inhabitants. It is also where the Vistula, the largest Polish river, ends its
course. In spring, large concentrations of 4-nonylphenol and 4-tert-octylphenol
were washed off into the coastal zone with meltwater. In summertime, sediments
near the beach had the highest alkylphenol concentrations (NP-2.31 ng g-1 dw, OP
13.09 ng g-1 dw), which was related to tourism and recreational activity. In silt
sediments located off the coast, the highest NP (1.46 ng g-1 dw) and OP (6.56 ng
g-1 dw) amounts were observed in autumn. The origin of OP and NP at those test
stations was linked to atmospheric transport of black carbon along with adsorbed
alkylphenols.
PMID- 25132693
TI - Sinorhizobium meliloti 1021 Exopolysaccharide as a Flocculant Improving
Chromium(III) Oxide Removal from Aqueous Solutions.
AB - Chromium(III) oxide is an amphoteric, dark green solid. This most stable dye is
widely used in construction and ceramic industries as well as in painting. In
this study, the attempt is made to determine flocculating properties of
exopolysaccharide (EPS) synthesized by the bacteria Sinorhizobium meliloti 1021,
which would increase the efficiency of chromium(III) oxide removal from sewages
and wastewaters. The conditions under which EPS is the most effective
destabilizing component of chromium(III) oxide suspension have been determined
too. In order to characterize the structure of electric double layer formed at
the solid/supporting electrolyte (EPS) solution interface, electrokinetic
potential measurements and potentiometric titration were performed. The EPS
amount adsorbed on the chromium(III) oxide surface as a solution pH function was
also measured. Moreover, the stability of Cr2O3 suspension in the absence and
presence of S. meliloti 1021 EPS was estimated. The pooled analysis of all
obtained results showed that EPS causes chromium(III) oxide suspension
destabilization in the whole examined pH range. The largest change in the system
stability before and after the polymer addition was observed at pH 9. It is
probable that under these conditions bridging flocculation occurs in the examined
system.
PMID- 25132694
TI - Coexistence of Legionella pneumophila Bacteria and Free-Living Amoebae in Lakes
Serving as a Cooling System of a Power Plant.
AB - The study was aimed at determining whether potentially pathogenic free-living
amoebae (FLA) and Legionella pneumophila can be found in lakes serving as a
natural cooling system of a power plant. Water samples were collected from five
lakes forming the cooling system of the power plants Patnow and Konin (Poland).
The numbers of investigated organisms were determined with the use of a very
sensitive molecular method-fluorescence in situ hybridization (FISH). The result
of the present study shows that thermally altered aquatic environments provide
perfect conditions for the growth of L. pneumophila and amoebae. The bacteria
were identified in the biofilm throughout the entire research period and in the
subsurface water layer in July and August. Hartmanella sp. and/or Naegleria
fowleri were identified in the biofilm throughout the entire research period.
PMID- 25132695
TI - A Cognitive-Social Model of Fertility Intentions.
AB - We examine the use and value of fertility intentions against the backdrop of
theory and research in the cognitive and social sciences. First, we draw on
recent brain and cognition research to contextualize fertility intentions within
a broader set of conscious and unconscious mechanisms that contribute to mental
function. Next, we integrate this research with social theory. Our
conceptualizations suggest that people do not necessarily have fertility
intentions; they form them only when prompted by specific situations. Intention
formation draws on the current situation and on schemas of childbearing and
parenthood learned through previous experience, imbued by affect, and organized
by self-representation. Using this conceptualization, we review apparently
discordant knowledge about the value of fertility intentions in predicting
fertility. Our analysis extends and deepens existing explanations for the weak
predictive validity of fertility intentions at the individual level and provides
a social-cognitive explanation for why intentions predict as well as they do.
When focusing on the predictive power of intentions at the aggregate level, our
conceptualizations lead us to focus on how social structures frustrate or
facilitate intentions and how the structural environment contributes to the
formation of reported intentions in the first place. Our analysis suggests that
existing measures of fertility intentions are useful but to varying extents and
in many cases despite their failure to capture what they seek to measure.
PMID- 25132696
TI - The Impact of School Connectedness and Teacher Support on Depressive Symptoms in
Adolescents: A Multilevel Analysis.
AB - Using data from Waves I and II of the National Longitudinal Study of Adolescent
Health (Add Health), this study examined the association between school
connectedness and teacher support and depressive symptoms in a weighted sample of
11,852 adolescents from 132 schools. To account for the nested data, multilevel
regression was utilized. The results indicated higher school connectedness and
getting along with teachers were significantly associated with fewer depressive
symptoms. Findings offer implications for school social work practice and future
research. Suggestions for future research are described and strategies to enhance
school connectedness and teacher support are discussed.
PMID- 25132697
TI - Complex Inequality: A Contextual Parenting Framework for Latino Infants.
PMID- 25132698
TI - Are there meaningful individual differences in temporal inconsistency in self
reported personality?
AB - The current project had three goals. The first was to examine whether it is
meaningful to refer to across-time variability in self-reported personality as an
individual differences characteristic. The second was to investigate whether
negative affect was associated with variability in self-reported personality,
while controlling for mean levels, and correcting for measurement errors. The
third goal was to examine whether variability in self-reported personality would
be larger among young adults than among older adults, and whether the relation of
variability with negative affect would be stronger at older ages than at younger
ages. Two moderately large samples of participants completed the International
Item Pool Personality questionnaire assessing the Big Five personality dimensions
either twice or thrice, in addition to several measures of negative affect.
Results were consistent with the hypothesis that within-person variability in
self-reported personality is a meaningful individual difference characteristic.
Some people exhibited greater across-time variability than others after removing
measurement error, and people who showed temporal instability in one trait also
exhibited temporal instability across the other four traits. However, temporal
variability was not related to negative affect, and there was no evidence that
either temporal variability or its association with negative affect varied with
age.
PMID- 25132700
TI - Using satellite remote sensing and household survey data to assess human health
and nutrition response to environmental change.
AB - Climate change and degradation of ecosystem services functioning may threaten the
ability of current agricultural systems to keep up with demand for adequate and
inexpensive food and for clean water, waste disposal and other broader ecosystem
services. Human health is likely to be affected by changes occurring across
multiple geographic and time scales. Impacts range from increasing
transmissibility and the range of vectorborne diseases, such as malaria and
yellow fever, to undermining nutrition through deleterious impacts on food
production and concomitant increases in food prices. This paper uses case studies
to describe methods that make use of satellite remote sensing and Demographic and
Health Survey data to better understand individual-level human health and
nutrition outcomes. By bringing these diverse datasets together, the connection
between environmental change and human health outcomes can be described through
new research and analysis.
PMID- 25132699
TI - Collaborative Mother-Toddler Communication and Theory of Mind Development at Age
4.
AB - Focusing on social pragmatics, this longitudinal study investigated the
contribution of mother-toddler collaborative communication to theory of mind
(ToM) development at age 4. At age 21/2, 78 toddlers' (42 boys) and their mothers
were observed during pretend play. At age 4, children were tested using 4 false
belief understanding tasks. Both mothers and toddlers engaged in more
collaborative (inform, guide/request, and support/confirm) than non-collaborative
communication acts. Other-focused collaborative acts of support/confirm by
mothers and toddlers predicted children's false belief understanding, even after
controlling for 5 covariates. In addition, as active agents in their own ToM
development, the contribution of toddlers' collaborative acts to false belief
understanding was independent of their mothers. Finally, the way toddlers and
their mothers co-constructing their communication mattered. Only when toddlers
engaged in high levels of collaborative acts, the mothers' high levels of
collaborative acts demonstrated a positive effect on children's ToM development.
The applied implications of these findings were discussed.
PMID- 25132701
TI - Empirical research on international environmental migration: a systematic review.
AB - This paper presents the findings of a systematic review of scholarly publications
that report empirical findings from studies of environmentally-related
international migration. There exists a small, but growing accumulation of
empirical studies that consider environmentally-linked migration that spans
international borders. These studies provide useful evidence for scholars and
policymakers in understanding how environmental factors interact with political,
economic and social factors to influence migration behavior and outcomes that are
specific to international movements of people, in highlighting promising future
research directions, and in raising important considerations for international
policymaking. Our review identifies countries of migrant origin and destination
that have so far been the subject of empirical research, the environmental
factors believed to have influenced these migrations, the interactions of
environmental and non-environmental factors as well as the role of context in
influencing migration behavior, and the types of methods used by researchers. In
reporting our findings, we identify the strengths and challenges associated with
the main empirical approaches, highlight significant gaps and future
opportunities for empirical work, and contribute to advancing understanding of
environmental influences on international migration more generally. Specifically,
we propose an exploratory framework to take into account the role of context in
shaping environmental migration across borders, including the dynamic and complex
interactions between environmental and non-environmental factors at a range of
scales.
PMID- 25132702
TI - Reassessing the Effects of Early Adolescent Alcohol Use on Later Antisocial
Behavior: A Longitudinal Study of Students in Victoria, Australia and Washington
State, United States.
AB - The effect of early adolescent alcohol use on antisocial behavior was examined at
one- and two-year follow-up in Washington, United States and Victoria, Australia.
Each state used the same methods to survey statewide representative samples of
students (N = 1,858, 52% female) in 2002 (Grade 7 [G7]), 2003 (Grade 8 [G8]), and
2004 (Grade 9 [G9]). Rates of lifetime, current, frequent, and heavy episodic
alcohol use were higher in Victoria than Washington State, whereas rates of five
antisocial behaviors were generally comparable across states. After controlling
for established risk factors, few associations between alcohol use and antisocial
behavior remained, except that G7 current use predicted G8 police arrests and
stealing and G9 carrying a weapon and stealing; G7 heavy episodic use predicted
G8 and G9 police arrests; and G7 lifetime use predicted G9 carrying a weapon.
Hence, risk factors other than alcohol were stronger predictors of antisocial
behaviors.
PMID- 25132704
TI - Marine actinomycete Streptomyces sp. ISP2-49E, a new source of Rhamnolipid.
PMID- 25132703
TI - Comparison of different blood collection, sample matrix, and immunoassay methods
in a prenatal screening setting.
AB - We compared how measurements of pregnancy-associated plasma protein A (PAPP-A)
and the free beta subunit of human chorionic gonadotropin (fbeta-hCG) in maternal
blood are influenced by different methods for blood collection, sample matrix,
and immunoassay platform. Serum and dried blood spots (DBS) were obtained by
venipuncture and by finger prick of 19 pregnant women. PAPP-A and fbeta-hCG from
serum and from DBS were measured by conventional indirect immunoassay on an
AutoDELFIA platform and by antibody microarray. We compared methods based on the
recoveries for both markers as well as marker levels correlations across samples.
All method comparisons showed high correlations for both marker concentrations.
Recovery levels of PAPP-A from DBS were 30% lower, while those of fbeta-hCG from
DBS were 50% higher compared to conventional venipuncture serum. The recoveries
were not affected by blood collection or immunoassay method. The high correlation
coefficients for both markers indicate that DBS from finger prick can be used
reliably in a prenatal screening setting, as a less costly and minimally invasive
alternative for venipuncture serum, with great logistical advantages.
Additionally, the use of antibody arrays will allow for extending the number of
first trimester screening markers on maternal and fetal health.
PMID- 25132705
TI - Effect of initial conditions on reproducibility of scientific research.
AB - BACKGROUND: It is estimated that about half of currently published research
cannot be reproduced. Many reasons have been offered as explanations for failure
to reproduce scientific research findings- from fraud to the issues related to
design, conduct, analysis, or publishing scientific research. We also postulate a
sensitive dependency on initial conditions by which small changes can result in
the large differences in the research findings when attempted to be reproduced at
later times. METHODS: We employed a simple logistic regression equation to model
the effect of covariates on the initial study findings. We then fed the input
from the logistic equation into a logistic map function to model stability of the
results in repeated experiments over time. We illustrate the approach by modeling
effects of different factors on the choice of correct treatment. RESULTS: We
found that reproducibility of the study findings depended both on the initial
values of all independent variables and the rate of change in the baseline
conditions, the latter being more important. When the changes in the baseline
conditions vary by about 3.5 to about 4 in between experiments, no research
findings could be reproduced. However, when the rate of change between the
experiments is <=2.5 the results become highly predictable between the
experiments. CONCLUSIONS: Many results cannot be reproduced because of the
changes in the initial conditions between the experiments. Better control of the
baseline conditions in-between the experiments may help improve reproducibility
of scientific findings.
PMID- 25132706
TI - Sensitivity of EUS and ERCP Endoscopic Procedures in the Detection of Pancreatic
Cancer During Preoperative Staging Correlated with CT and CT Angiography Imaging
Methods.
AB - THE GOAL: The goal of this work was to give advantage to EUS as endoscopic method
in diagnosis and following therapeutic treatment of pancreatic cancer in relation
to radiological methods of CT and CTA. MATERIAL AND METHODS: The study included
49 patients, 20 women and 29 men hospitalized at the Clinic for
gastroenterohepatology, due to suspicion on pancreatic cancer during observed 2
years period. All cancers were histologically and cytologically confirmed. The
patients underwent ERCP as a mandatory part of staging and all patients underwent
endoscopic ultrasound as well as CT or CT angiography. RESULTS: Testing of
differences was carried out using Fisher's exact test in open-source software R.
The following characteristics were tested: involvement of the blood vessels,
lymph nodes, metastases, tumor size and duodenum infiltration. Results showed
statistically significant difference at the 0.05 level for EUS, CT and CT
angiography. Risk ratio showed that EUS is less effective in detecting
infiltration of blood vessels within a malignant process then CTA where RR=0.52,
CI 0.2-1.38, p-value=0.33. EUS and CTA are equal in the diagnosis of enlarged
lymph nodes affected by malignancy where RR=1.3, CI 0.75-1.42, p-value=0.09.
Comparison according to distant metastases showed that EUS is less effective
compared to CT in approximately 30% of cases. In the diagnosis of duodenal
infiltration EUS is in 5% of cases less accurate than the CT with the RR=0.95, CI
0.27-3.32, p-value=0.76, but the CTA method is more efficient because the
comparison of EUS and CTA showed RR=12.52, CI 0.2-1.38, p-value=0.33. EUS as a
diagnostic method is dominant in determining the size of malignant lesions
located in the pancreas as compared to CT and CTA. CONCLUSION: EUS as endoscopic
method compared to CT and CTA is one of the more invasive methods of examination
but due to its ability to be performed immediately, to locate a changes smaller
than 5 mm and the target biopsy option, to measure the change and that in many
cases determine the relationship of malignant lesions with blood vessels, along
with visualization of the surrounding lymph nodes and metastases in neighboring
organs, we may give this method an advantage over other methods in the
preoperative staging of patients with pancreatic cancer.
PMID- 25132707
TI - Colonoscopy as a method of choice in the diagnosis of colorectal cancer.
AB - INTRODUCTION: Epidemiological characteristics of colorectal cancer indicate that
in the U.S. colorectal cancer is the second leading cause of death from
malignancy, just behind lung cancer. In the 2000 there were approximately 130,200
new cases, of which 56,300 had lethal outcome. In the past 15 years, the
incidence and mortality rate has been declining, especially in women. Colorectal
cancer is mainly found in people older than 50 years. Carcinoembryonic antigen
(CEA) is insufficiently specific for the early detection of the disease. Its
normal value is less than 5 g/L in the serum. Elevated levels of CEA after
surgery indicate a lack of radical surgery, residual neoplasm, hidden distant
metastases or recurrent disease. Unfortunately, only 10-15% of patients with
recurrent disease can be successfully re-operated (isolated metastases in the
liver or lungs). Colorectal cancer is predominantly adenocarcinoma, the tumor has
relatively slow growth. While symptoms occur relatively early, distant metastases
have relatively late appearance. GOALS: The goals of this study were to remind
the fundamental facts about the nature of this disease, to stress the importance
of early detection of BC-screening programs, to draw attention to contemporary
attitudes in the field of diagnosis and treatment of colorectal cancer, and to
show the experience in the treatment of this disease at the Surgical Departments
of the General Hospital in Konjic. RESULTS: In the period from 2008-2012 years,
at the Surgical Department of the General Hospital in Konjic surgically treated
are 34 patients who had colorectal malignancy. There were 21 (65 %) male and 13
females (35%). All patients belonged to the age group of 50-75 years. Only five
patients or 15 % prior to admission to the hospital had been diagnosed with a
malignant process. All others, or 85% of the total sample, were admitted to the
hospital as emergency cases (erosive gastritis), and after, shorter preparation
underwent surgery. Only five (15%) of patients were admitted electively, already
diagnosed with colorectal tumors by colonoscopy. Total number of lethal outcomes
at the department was 8 (24%). Three patients died due to cardio-respiratory
failure and MOF, and 5 patients due to anastomotic failure and septic shock.
CONCLUSION: In conclusion we can say that in our institution it is necessary to
obtain the proper equipment (colonoscope) and educate personnel, so we can
introduce colonoscopy as the mandatory screening method of examination,
particularly for vulnerable groups.
PMID- 25132708
TI - Endoscopic management of vesicoureteral reflux in children in kosova.
AB - INTRODUCTION: Vesicoureteral reflux (VUR) in children has been treated with
subureteric deflux injection of Deflux (dextranomer hyaluronic acid copolymer)
since 2009. The aim of this study was to analyze the results of endoscopic
treatment of VUR in our clinic. METHODS: Between March 2009 and December 2013,
fifty-five children underwent endoscopic subureteral injection of Deflux in 78
ureters. Two months postoperatively voiding cystourethrogram (VCUG) was
performed. This study examined the disappearance of VUR and urinary tract
infection (UTI) as well as the quality of life during long-term follow-up.
RESULTS: The study included 55 patients (40 females and 15 males) with 78
refluxing ureters. There were 22 refluxed ureters altogether and 33 children had
a unilateral reflux (two duplicated systems). All patients were treated, from the
age 6 months up to 12 years old. The mean age of patients was 5.2 years. There
has been no complications, but with few recurrences. In 6 patients (16.6%),
endoscopic treatment with deflux was done twice, while in three patients (8.5%),
the endoscopic treatment with deflux was performed three times, because of
recurrence. CONCLUSION: We recommend the use of endoscopic Deflux injection as
first line treatment for children with VUR. Endoscopic subureteral injection of
Deflux is a minimally invasive method for VUR treatment in pediatric patients and
is associated with low morbidity.
PMID- 25132709
TI - Potential Role of Lung Ventilation Scintigraphy in the Assessment of COPD.
AB - OBJECTIVE: To highlight the importance of the lung ventilation scintigraphy (LVS)
to study the regional distribution of lung ventilation and to describe most
frequent abnormal patterns of lung ventilation distribution obtained by this
technique in COPD and to compare the information obtained by LVS with the that
obtained by traditional lung function tests. MATERIAL AND METHODS: The research
was done in 20 patients with previously diagnosed COPD who were treated in
Intensive care unit of Clinic for pulmonary diseases and TB "Podhrastovi"
Clinical Center, University of Sarajevo in exacerbation of COPD during first
three months of 2014. Each patient was undergone to testing of pulmonary function
by body plethysmography and ventilation/perfusion lung scintigraphy with radio
pharmaceutics Technegas, 111 MBq Tc -99m-MAA. We compared the results obtained by
these two methods. RESULTS: All patients with COPD have a damaged lung function
tests examined by body plethysmography implying airflow obstruction, but LVS
indicates not only airflow obstruction and reduced ventilation, but also
indicates the disorders in distribution in lung ventilation. CONCLUSION: LVS may
add further information to the functional evaluation of COPD to that provided by
traditional lung function tests and may contribute to characterizing the
different phenotypes of COPD.
PMID- 25132710
TI - Importance of Alpha-adrenergic Receptor Subtypes in Regulating of Airways Tonus
at Patients with Bronchial Asthma.
AB - BACKGROUND: In this work, effect of Tamsulosin hydrochloride as antagonist of
alpha1A and alpha1B- adrenergic receptor and effect of Salbutamol as agonist of
beta2- adrenergic receptor in patients with bronchial asthma and increased
bronchial reactibility was studied. METHODS: Parameters of the lung function are
determined by Body plethysmography. Raw and ITGV were registered and specific
resistance (SRaw) was also calculated. Tamsulosin was administered in per os way
as a preparation in the form of the capsules with a brand name of "Prolosin",
producer: Niche Generics Limited, Hitchin, Herts. RESULTS: Results gained from
this research show that blockage of alpha1A and alpha1B- adrenergic receptor with
Tamsulosin hydrochloride (0.4 mg and 0.8 mg in per os way) has not changed
significantly (p > 0.1) the bronchomotor tonus of tracheobronchial tree in
comparison to the inhalation of Salbutamol as agonist of beta2- adrenergic
receptor (2 inh. x 0.2 mg), (p < 0.05). Arterial blood pressure showed no
significant decrease following the administration of the dose of 0.8 mg
Tamsulosin. CONCLUSION: This suggests that the activity of alpha1A and alpha1B-
adrenergic receptor in the smooth musculature is not a primary mechanism which
causes reaction in patients with increased bronchial reactibility, in comparison
to agonists of beta2 - adrenergic receptor which emphasizes their significant
action in the reduction of specific resistance of airways.
PMID- 25132711
TI - A Survey on the Users' Satisfaction with the Hospital Information Systems (HISs)
based on DeLone and McLean's Model in the Medical-Teaching Hospitals in Isfahan
City.
AB - BACKGROUND AND PURPOSE: The user's satisfaction with information system in fact
denotes the extent the user is satisfied with the system's achievement in
fulfilling his/her information requirements. This study tries to explore the
users' satisfaction with hospital information systems (HISs) based on DeLone and
McLean's model focusing on the medical-teaching hospitals of Isfahan city.
METHODOLOGY: This study which was applied and descriptive-analytical in nature
was carried out in the medical-teaching hospitals of Isfahan city in 2009.
Research population consisted of the system users from which a sample was
selected using random sampling method. The size of the sample was 228. Data
collection instrument was a self-developed questionnaire produced based on the
satisfaction criterion in the DeLone and McLean's model. Its content validity was
assessed based on the opinions given by the computer sciences professionals with
its estimated Cronbach's alpha found to be 92.2%. The data were analyzed using
SPSS software. FINDINGS: As the findings of the study showed, the differences
among the mean scores obtained for the satisfaction with different kinds of HISs
in use in the hospitals were statistically significant (p value<=0.05).
Generally, Kowsar System (old version) and Pouya Samaneh Diva system gained the
highest and lowest mean scores for the criterion in question, respectively. The
overall mean score for the satisfaction was 54.6% for different types of systems
and 55.6% among the hospitals. CONCLUSION: Given the findings of the study, it
can be argued that based on the used model, the level of users' satisfaction with
the systems in question was relatively good. However, to achieve the total
optimum condition, when designing the system, the factors affecting the
enhancement of the users' satisfaction and the type of hospital activity and
specialty must be given special consideration.
PMID- 25132712
TI - Quality assessment of persian mental disorders websites using the webmedqual
scale.
AB - INTRODUCTION: Nowadays, anyone with any level of Internet knowledge can act as
producer and distributor of information. It differs from most traditional media
of information transmission, lack of information control and lack of quality
management to contents. This leads to quality of health information on the
internet is doubtful. The object of this study is guidance patients to select
valid mental disorders and determine the quality of Persian mental disorders
websites. METHODS: The sample of this study comprised 29 Persian mental disorders
websites that were chosen by searching the Google, Yahoo and AltaVista search
engines for the Persian equivalents of the three concepts "depression,"
"anxiety," and "obsession". website was created by individuals or organizations.
Data collection was performed with the WebMedQual checklist. Websites was
assessed based on indicators as content, authority of source, design,
accessibility and availability, links, user support, and confidentiality and
privacy (Maximum score for any website was 83, mean score 41.5 and minimum score
was 0). Collected data analyzed by one sample T- test in SPSS 20. Findings
presented by Mean score and optimal score. RESULTS: Based on the WebMedQual scale
the mean score of Persian mental disorders websites in sex constructs including
"content" (7.02+/-2.10), "authority of source" (4.71+/-1.96),"accessibility and
availability" (2.19+/-0.47), "links" (1.45+/-0.97), "user support" (4.28+/-1.33),
and"confidentiality and privacy" (2.81+/-2.81) are poor and below average, but
the score for the "design" (9.17+/- 1.59) is above average. The best website of
mental disorders was that of the "IranianPsychological Association". CONCLUSIONS:
According to the results, only one website obtained the average score, so the
quality of Persian mental disorders websites is low. Therefore, it is essential
for users to criticize websites' content and not trust them before evaluating
them. It is better to use the ranked list websites or search on the internet by
help information experts.
PMID- 25132713
TI - Medical universities educational and research online services: benchmarking
universities' website towards e-government.
AB - BACKGROUND: Websites as one of the initial steps towards an e-government adoption
do facilitate delivery of online and customer-oriented services. In this study we
intended to investigate the role of the websites of medical universities in
providing educational and research services following the E-government maturity
model in the Iranian universities. METHODS: This descriptive and cross- sectional
study was conducted through content analysis and benchmarking the websites in
2012. The research population included the entire medical university website
(37). Delivery of educational and research services through these university
websites including information, interaction, transaction, and Integration were
investigated using a checklist. The data were then analyzed by means of
descriptive statistics and using SPSS software. RESULTS: Level of educational and
research services by websites of the medical universities type I and II was
evaluated medium as 1.99 and 1.89, respectively. All the universities gained a
mean score of 1 out of 3 in terms of integration of educational and research
services. CONCLUSIONS: Results of the study indicated that Iranian universities
have passed information and interaction stages, but they have not made much
progress in transaction and integration stages. Failure to adapt to e-government
in Iranian medical universities in which limiting factors such as users' e
literacy, access to the internet and ICT infrastructure are not so crucial as in
other organizations, suggest that e-government realization goes beyond technical
challenges.
PMID- 25132714
TI - Scientific production of Sports Science in Iran: A Scientometric Analysis.
AB - BACKGROUND: Physical education and sports science is one of the branches of
humanities. The purpose of this study is determining the quantitative and
qualitative rate of progress in scientific Production of Iran's researcher in Web
of Science. METHODS: Research Methods is Scientometric survey and Statistical
Society Includes 233 Documents From 1993 to 2012 are indexed in ISI. RESULTS:
Results showed that the time of this study, Iranian researchers' published 233
documents in this base during this period of time which has been cited 1106(4.76
times on average). The H- index has also been 17. Iran's most scientific
productions in sports science realm was indexed in 2010 with 57 documents and the
least in 2000. CONCLUSIONS: By considering the numbers of citations and the
obtained H- index, it can be said that the quality of Iranian's articles is
rather acceptable but in comparison to prestigious universities and large number
of professors and university students in this field, the quantity of outputted
articles is very low.
PMID- 25132715
TI - Contribution of Indian pediatric dentists to scientific literature during 2002
2012: a bibliometric analysis.
AB - INTRODUCTION: Bibliometric analysis of publications is necessary to enable
clinicians to make evidence based sound clinical decisions. It will also help
policy makers & institutions to frame their decisions and policies so as to
improve the quality of dental research in India. AIM: The purpose of this study
is to identify publication output as well as descriptively and quantitatively
characterize the contribution of Indian pediatric dentists to scientific
literature through publication trend analysis from 2002 to 2012. SETTINGS AND
DESIGN: Cross sectional analytical study. MATERIAL AND METHOD: A bibliometric
analysis of publications by Indian pediatric dentists during 2002 to 2012 was
performed on data collected from PubMed - MEDLINE database. Only the first
author's affiliations were considered and the publications were categorized
according to the following variables: year of publication, number of authors,
state of origin, type of article, reach of journal and country of publication.
RESULTS: There were 817 articles by Indian pediatric dentists during the study
period. Of all the articles 399 (48.8%) were original research, 377(46.1%) were
case reports and 41 (5.0%) were reviews. The inter-annual variation between the
reach, country of publication of the journal and type of articles is presented.
The growth trend analysis was performed and predictions are presented.
CONCLUSION: There has been an increase in the number of publications by Indian
pediatric dentists and most of the published work comprises of original research.
The potential use of this data is discussed.
PMID- 25132716
TI - Changes in the Muscle Strength of the Elbow Flexors Following a Six-week
Experimental Procedure in Adolescents Monitored Through Isokinetic and Motor
Tests.
AB - A group of 7 subjects underwent an experimental procedure which studied the
potential changes in the maximal strength of the non-dominant arm elbow flexors.
The programme duration was limited to 6 weeks during which the subjects practiced
exercises 3 times a week, 3 series, on a Scott bench. Individual approach was
applied to the external load and it was designed so that the weight being lifted
would increase if the number of lifts in one series would exceed 3. The subjects
were monitored through the one-repetition maximum 1 RM motor test and the
isokinetic tests performed on biodex system, tested in 3 time periods (at the
beginning, after 3 weeks, and after the 6th week). Of the 6 isokinetic tests,
only the test for the maximum torque and the time for achieving the maximum
torque have shown statistically important changes in terms of reduction in
values, which was not expected. The one-repetition maximum test, unlike the
isokinetic tests, has shown statistically important increase of the maximal
muscle strength of 32.1% after the third week of exercising, and 46.8% after the
six weeks of exercising. The statistical test for the correlation between the two
variables has shown low correlation between these two tests. The values of the
data of the two test types have not shown any correspondence among the subjects
possibly due to the type of performance of the maximal muscle load during
exercises, performed in conditions identical to the one-repetition maximum test,
with similar and yet different conditions in the case of isokinetic tests. Most
probably, due to the conditions in which the exercises and the tests took place,
there is difference in the obtained results.
PMID- 25132717
TI - The Use of Smart phones in Ophthalmology.
AB - Smart phones are being increasingly used among health professionals.
Ophthalmological applications are widely available and can turn smart phones into
sophisticated medical devices. Smart phones can be useful instruments for the
practice of evidence-based medicine, professional education, mobile clinical
communication, patient education, disease self-management, remote patient
monitoring or as powerful administrative tools. Several applications are
available for different ophthalmological examinations that can assess visual
acuity, color vision, astigmatism, pupil size, Amsler grid test and more. Smart
phones can be useful ophthalmic devices for taking images of anterior and
posterior eye segment. Professional literature and educational material for
patients are easily available with use of smart phones. Smart phones can store
great amount of informations and are useful for long term monitoring with caution
for patient confidentiality. The use of smart phones especially as diagnostic
tools is not standardized and results should be carefully considered. Innovative
role of smartphone technology and its use in research, education and information
sharing makes smart phones a future of ophthalmology and medicine.
PMID- 25132718
TI - EASE Guidelines for Authors and Translators of Scientific Articles to be
Published in English.
AB - This concise and readable set of editorial guidelines was first published by the
European Association of Science Editors (EASE) in 2010 and is updated annually.
It is freely available in more than 20 languages at
http://ease.org.uk/publications/author-guidelines. The document is aimed to help
scientists worldwide in successful presentation of their research results and in
correct translation of manuscripts into English. Moreover, it draws attention to
ethical issues, like authorship criteria, plagiarism, conflict of interests, etc.
Eight appendices provide examples or more detailed information on selected topics
(Abstracts, Ambiguity, Cohesion, Ethics, Plurals, Simplicity, Spelling, and Text
tables). Widespread use of EASE Guidelines should increase the efficiency of
international scientific communication.
PMID- 25132719
TI - Enhanced Electro-Static Modulation of Ionic Diffusion through Carbon Nanotube
Membranes by Diazonium Grafting Chemistry.
AB - A membrane structure consisting of an aligned array of open ended carbon
nanotubes (~ 7 nm i.d.) spanning across an inert polymer matrix allows the
diffusive transport of aqueous ionic species through CNT cores. The plasma
oxidation process that opens CNTs tips inherently introduces carboxylic acid
groups at the CNT tips, which allows for a limited amount of chemical functional
at the CNT pore entrance. However for numerous applications, it is important to
increase the density of carboxylic acid groups at the pore entrance for effective
separation processes. Aqueous diazonium based electro-chemistry significantly
increases the functional density of carboxylic acid groups. pH dependent dye
adsorption-desorption and interfacial capacitance measurements indicate ~ 5-6
times increase in functional density. To further control the spatial location of
the functional chemistry, a fast flowing inert liquid column inside the CNT core
is found to restrict the diazonium grafting to the CNT tips only. This is
confirmed by the increased flux of positively charged Ru(bi-py)3+2 with anionic
functionality. The electrostatic enhancement of ion diffusion is readily screened
in 0.1(M) electrolyte solution consistent with the membrane pore geometry and
increased functional density.
PMID- 25132720
TI - Psychometric Evaluation of the Social Problem-Solving Inventory- Revised among
Overweight or Obese Adults.
AB - Problem solving is a key component of weight loss programs. The Social Problem
Solving Inventory-Revised (SPSI-R) has not been evaluated in weight loss studies.
The purpose of this study was to evaluate the psychometrics of the SPSI-R.
Cronbach's alpha (.95 for total score; .67 - .92 for subscales) confirmed
internal consistency reliability. The SPSI-R score was significantly associated
(ps<.05) with decreased eating barriers and binge eating, increased self-efficacy
in following a cholesterol-lowering diet, consumption of fewer calories and fat
grams, more frequent exercise, lower psychological distress, and higher mental
quality of life; all suggesting concurrent validity with other instruments used
in weight loss studies. However, confirmatory factor analysis of the hypothesized
5-factor structure did not fit the data well (chi2=350, p<.001).
PMID- 25132721
TI - Novel Method of Measuring Cantilever Deflection during an AFM Force Measurement.
AB - A combination of a reflection interference contrast microscope (RICM) and the
atomic force microscope (AFM) was used to monitor the cantilever-surface
separation distance during force measurements using the streptavidin-biotin
recognition pairs. The RICM showed that the cantilever loses contact with the
surface before the final rupture of the adhesive bonds is measured by the AFM
detection system. This finding suggests that the immobilization of biotin by
physisorbed albumin and subsequent binding of streptavidin might have created a
cross-linked protein network whose cohesion is tested by the AFM cantilever with
the immobilized biotin ligands.
PMID- 25132722
TI - Writing fluency and quality in kindergarten and first grade: The role of
attention, reading, transcription, and oral language.
AB - In the present study, we examined the influence of kindergarten component skills
on writing outcomes, both concurrently and longitudinally to first grade. Using
data from 265 students, we investigated a model of writing development including
attention regulation along with students' reading, spelling, handwriting fluency,
and oral language component skills. Results from structural equation modeling
demonstrated that a model including attention was better fitting than a model
with only language and literacy factors. Attention, a higher-order literacy
factor related to reading and spelling proficiency, and automaticity in letter
writing were uniquely and positively related to compositional fluency in
kindergarten. Attention and higher-order literacy factor were predictive of both
composition quality and fluency in first grade, while oral language showed unique
relations with first grade writing quality. Implications for writing development
and instruction are discussed.
PMID- 25132723
TI - Abnormal Image Detection in Endoscopy Videos Using a Filter Bank and Local Binary
Patterns.
AB - Finding mucosal abnormalities (e.g., erythema, blood, ulcer, erosion, and polyp)
is one of the most essential tasks during endoscopy video review. Since these
abnormalities typically appear in a small number of frames (around 5% of the
total frame number), automated detection of frames with an abnormality can save
physician's time significantly. In this paper, we propose a new multi-texture
analysis method that effectively discerns images showing mucosal abnormalities
from the ones without any abnormality since most abnormalities in endoscopy
images have textures that are clearly distinguishable from normal textures using
an advanced image texture analysis method. The method uses a "texton histogram"
of an image block as features. The histogram captures the distribution of
different "textons" representing various textures in an endoscopy image. The
textons are representative response vectors of an application of a combination of
Leung and Malik (LM) filter bank (i.e., a set of image filters) and a set of
Local Binary Patterns on the image. Our experimental results indicate that the
proposed method achieves 92% recall and 91.8% specificity on wireless capsule
endoscopy (WCE) images and 91% recall and 90.8% specificity on colonoscopy
images.
PMID- 25132724
TI - Feasibility of measuring antigen-antibody interaction forces using a scanning
force microscope.
AB - The molecular affinity scanning force microscopy (MASFM) described in this study
was developed in an effort to test the possibility of antigen-antibody binding
measurement using force-separation distance profiles. The MASFM configuration was
comprised of a spherical glass bead as an MASFM probe, to which the fluorescein
antigen has been covalently attached, and a silicon dioxide-based substrate, to
which the antifluorescyl IgG antibody was covalently bound. The bead was glued to
the tip of a commercial SFM cantilever. Adhesion forces have been measured
between two different specific antigen-antibody pairs and between nonspecific
surfaces bearing only glycidoxypropylsilane immobilization chemistry. In force
separation (F-s) measurements, nonspecific forces displayed relatively few force
discontinuities and mean adhesion forces lower than those found for specific
antigen-antibody measurements. Force-separation profiles measured between
specific antigen-antibody pairs showed many discontinuities and had higher mean
forces. Positive controls revealed that the mean forces were slightly reduced by
the addition of free ligand. The magnitude of mean forces did not correlate with
the respective activation enthalpies of the proteins, as would be expected. At
lower force values the force histograms for the specific pairs and for positive
controls were indistinguishable. None of the force-separation data sets could fit
a Poisson discrete-force model. This statistical analysis showed a large relative
contribution from nonspecific interactions. It is concluded that the use of the
large sphere as an SFM probe is counterproductive: while the large sphere does
sample a larger number of specific interactions during each measurement, it also
samples at the same time a large proportion of nonspecific forces. The presence
of the nonspecific force contributions is likely due to the deformation of the
polymerized GPS spacer layer which is thought to be delaminated from the surface
upon the application of tension across the specific antigen-antibody bonds.
PMID- 25132725
TI - The desorption of ribonuclease A from charge density gradient surfaces studied by
spatially-resolved total internal reflection fluorescence.
AB - A quaternary amine surface gradient was prepared on fused silica by a three-step
surface modification process. The gradient surface displayed a transition of
surface charges along the gradient dimension from a net negative surface charge
of silica to a net positive surface charge at the quaternary amine end. The
gradient surface was characterized by X-ray photoelectron spectroscopy,
ellipsometry, colloidal gold decoration, and dynamic contact angle measurements.
It displayed an increased adhesion of negatively charged gold particles towards
the quaternary amine end. The water contact angles also increased with the
increased surface density of aminopropylsilyl groups. The desorption of
ribonuclease A labeled with fluorescein-5-isothiocyanate (FITC-RNase) from the
quaternary amine gradient surface was measured using spatially resolved total
internal reflection fluorescence (TIRF) spectroscopy. The experimental FITC-RNase
desorption results fitted exceptionally well to a two adsorbed protein
populations model. A tentative assignment of the two adsorbed protein populations
is proposed based on the effect of the ionic strength of the desorbing buffer.
The faster desorption population interacted primarily with the quaternary amine
gradient surface sites through electrostatic interactions. The slower desorption
population interacted with the surface sites via hydrophobic and possibly some
electrostatic interactions.
PMID- 25132726
TI - Chemical pattern on silica surface prepared by UV irradiation of 3
mercaptopropyltriethoxy silane layer: surface characterization and fibrinogen
adsorption.
AB - A flat silica surface modified with 3-mercaptopropyltriethoxy silane (MTS) was
patterned using UV irradiation and a custom-designed mask. The irradiated surface
was characterized by X-ray photoelectron spectroscopy (XPS), scanning force
microscopy (SFM) and water contact angle measurements. The XPS S2p spectra
indicated that the UV treatment resulted in the oxidation of MTS sulfur. The
optimal UV irradiation dose for patterning, estimated from the XPS S2p binding
energy shifts and water contact angles of irradiated surfaces, was 4.8 J cm-2 at
270 nm. The surface patterns were visualized by total internal reflection
fluorescence microscopy, while exposing the pattern to a solution of acridine
orange, by water vapor condensation, and by SFM lateral force imaging in dilute
electrolyte solution. The adhesion SFM measurements revealed the adhesion force
only on the areas which were not UV-irradiated. The adsorption of fluorescein
labeled fibrinogen (FITC-Fgn) from dilute buffer solution also produced visual
information on the pattern. The kinetics of FITC-Fgn adsorption onto the oxidized
and unoxidized MTS-silica surfaces from dilute protein solution proceeded with
identical initial adsorption rates. The steady-state FITC-Fgn adsorption was
twice as large on the unoxidized MTS-silica than on the oxidized MTS-silica
surface.
PMID- 25132727
TI - Maternal Social Coaching Quality Interrupts the Development of Relational
Aggression During Early Childhood.
AB - Previous research has shown that parents of socially competent young children
provide them with elaborative, explicit, appropriate and emotion-laden advice
about peer interactions. The current study analyzed mothers' conversations with
preschoolers (N=175; 52% female; M age = 52 months, SD = 7 months) about peer
conflicts involving relational aggression. Conversations were coded for maternal
elaboration, emotion references, and discussion of norm violations. Information
about relational and physical aggression was collected from teachers at two
assessments approximately 12 months apart for a subsample of 136 children.
Regression analyses, controlling for physical aggression, showed that average and
high levels of effective coaching operated as a protective factor against stable
high levels of relational aggression. Theoretical and practical implications for
our understanding of the early development of relational aggression are
discussed.
PMID- 25132728
TI - YKL-40 as a novel factor associated with inflammation and catabolic mechanisms in
osteoarthritic joints.
AB - YKL-40 is associated with tissue injury and inflammation, and consequently to
diseases in which these mechanisms lead to tissue degradation, for example,
asthma and rheumatoid arthritis. The purpose of the present study was to
investigate if YKL-40 is also a significant factor in osteoarthritis (OA) by
assessing associations of YKL-40 with mediators related to the pathogenesis of
OA: cartilage destructing matrix metalloproteinases (MMPs) and proinflammatory
cytokines interleukin-6 (IL-6) and interleukin-17 (IL-17). Cartilage, synovial
fluid (SF), and plasma samples were obtained from 100 OA patients undergoing
total knee replacement surgery. SF levels of YKL-40 (1027.9 +/- 78.3 ng/mL) were
considerably higher than plasma levels (67.2 +/- 4.5 ng/mL) and correlated with
YKL-40 released from cartilage samples obtained from the same patients (r = 0.37,
P = 0.010), indicating that YKL-40 is produced by OA cartilage. Interestingly,
YKL-40 concentrations in OA SF correlated positively with MMP-1 (r = 0.36, P =
0.014), MMP-3 (r = 0.46, P = 0.001), IL-6 (r = 0.57, P < 0.001), and IL-17 (r =
0.52, P = 0.010) levels. Moreover, IL-6 and IL-17 enhanced YKL-40 production in
human primary chondrocyte cultures. The present study introduces YKL-40 as a
cartilage-derived factor associated with mediators of inflammation and cartilage
destruction involved in the pathogenesis of OA.
PMID- 25132729
TI - Relationship between early inflammatory response and clinical evolution of the
severe multiorgan failure in mechanical circulatory support-treated patients.
AB - BACKGROUND: The mechanical circulatory support (MCS) is an effective treatment in
critically ill patients with end-stage heart failure (ESHF) that, however, may
cause a severe multiorgan failure syndrome (MOFS) in these subjects. The impact
of altered inflammatory response, associated to MOFS, on clinical evolution of
MCS postimplantation patients has not been yet clarified. METHODS: Circulating
cytokines, adhesion molecules, and a marker of monocyte activation (neopterin)
were determined in 53 MCS-treated patients, at preimplant and until 2 weeks. MOFS
was evaluated by total sequential organ failure assessment score (tSOFA).
RESULTS: During MCS treatment, 32 patients experienced moderate MOFS (tSOFA < 11;
A group), while 21 patients experienced severe MOFS (tSOFA >= 11) with favorable
(B group) or adverse (n = 13, C group) outcomes. At preimplant, higher values of
left ventricular ejection fraction (LVEF) and estimated glomerular filtration
rate (eGFR) were the only parameter independently associated with A group. In C
group, during the first postoperative week, high levels of interleukin-8 (IL-8)
and tumor necrosis factor (TNF)-alpha, and an increase of neopterin and adhesion
molecules, precede tSOFA worsening and exitus. CONCLUSIONS: The MCS patients of C
group show an excessive release to IL-8 and TNF-alpha, and monocyte-endothelial
activation after surgery, that might contribute to the unfavourable evolution of
severe MOFS.
PMID- 25132730
TI - Macrophage trafficking as key mediator of adenine-induced kidney injury.
AB - Macrophages play a special role in the onset of several diseases, including acute
and chronic kidney injuries. In this sense, tubule interstitial nephritis (TIN)
represents an underestimated insult, which can be triggered by different stimuli
and, in the absence of a proper regulation, can lead to fibrosis deposition.
Based on this perception, we evaluated the participation of macrophage
recruitment in the development of TIN. Initially, we provided adenine-enriched
food to WT and searched for macrophage presence and action in the kidney. Also, a
group of animals were depleted of macrophages with the clodronate liposome while
receiving adenine-enriched diet. We collected blood and renal tissue from these
animals and renal function, inflammation, and fibrosis were evaluated. We
observed higher expression of chemokines in the kidneys of adenine-fed mice and a
substantial protection when macrophages were depleted. Then, we specifically
investigated the role of some key chemokines, CCR5 and CCL3, in this TIN
experimental model. Interestingly, CCR5 KO and CCL3 KO animals showed less renal
dysfunction and a decreased proinflammatory profile. Furthermore, in those
animals, there was less profibrotic signaling. In conclusion, we can suggest that
macrophage infiltration is important for the onset of renal injury in the adenine
induced TIN.
PMID- 25132731
TI - Oral administration of herbal mixture extract inhibits 2,4-dinitrochlorobenzene
induced atopic dermatitis in BALB/c mice.
AB - CP001 is four traditional herbal medicine mixtures with anti-inflammatory
properties. In this study, we investigated the effect of oral administration of
CP001 ethanol extract on the 2,4-dinitrochlorobenzene- (DNCB-) induced AD mouse
models. For that purpose, we observed the effects of oral administration of CP001
on skin inflammatory cell infiltration, skin mast cells, production of serum IgE,
and expression of Th2 cytokine mRNA in the AD skin lesions of DNCB treated BALB/c
mice. Histological analyses demonstrated that CP001 decreased dermis and
epidermis thickening as well as dermal infiltration induced by inflammatory
cells. In addition, CP001 decreased mast cell infiltration in count as well as
dermal infiltration induced by inflammatory cells. In the skin lesions, mRNA
expression of interleukin- (IL-) 4 and IL-13 was inhibited by CP001. CP001 also
reduced the production of IgE level in mouse plasma. In addition, we investigated
the effect of CP001 on the inflammatory allergic reaction using human mast cells
(HMC-1). In HMC-1, cytokine production and mRNA levels of IL-4, IL-13, IL-6, and
IL-8 were suppressed by CP001. Taken together, our results showed that oral
administration of CP001 exerts beneficial effects in AD symptoms, suggesting that
CP001 might be a useful candidate for the treatment of AD.
PMID- 25132735
TI - Circumsporozoite protein-specific K(d)-restricted CD8+ T cells mediate protective
antimalaria immunity in sporozoite-immunized MHC-I-K(d) transgenic mice.
AB - Although the roles of CD8+ T cells and a major preerythrocytic antigen, the
circumsporozoite (CS) protein, in contributing protective antimalaria immunity
induced by radiation-attenuated sporozoites, have been shown by a number of
studies, the extent to which these players contribute to antimalaria immunity is
still unknown. To address this question, we have generated C57BL/6 (B6)
transgenic (Tg) mice, expressing K(d) molecules under the MHC-I promoter, called
MHC-I-K(d)-Tg mice. In this study, we first determined that a single immunizing
dose of IrPySpz induced a significant level of antimalaria protective immunity in
MHC-I-K(d)-Tg mice but not in B6 mice. Then, by depleting various T-cell subsets
in vivo, we determined that CD8+ T cells are the main mediator of the protective
immunity induced by IrPySpz. Furthermore, when we immunized (MHC-I-K(d)-Tg * CS
Tg) F1 mice with IrPySpz after crossing MHC-I-K(d)-Tg mice with PyCS-transgenic
mice (CS-Tg), which are unable to mount PyCS-specific immunity, we found that
IrPySpz immunization failed to induce protective antimalaria immunity in (MHC-I
K(d)-Tg * CS-Tg) F1 mice, thus indicating the absence of PyCS antigen-dependent
immunity in these mice. These results indicate that protective antimalaria
immunity induced by IrPySpz in MHC-I-K(d)-Tg mice is mediated by CS protein
specific, K(d)-restricted CD8+ T cells.
PMID- 25132732
TI - Purinergic receptors in ocular inflammation.
AB - Inflammation is a complex process that implies the interaction between cells and
molecular mediators, which, when not properly "tuned," can lead to disease. When
inflammation affects the eye, it can produce severe disorders affecting the
superficial and internal parts of the visual organ. The nucleoside adenosine and
nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides
such as P(1),P(4)-diadenosine tetraphosphate (Ap4A), and P(1),P(5)-diadenosine
pentaphosphate (Ap5A) are present in different ocular locations and therefore
they may contribute/modulate inflammatory processes. Adenosine receptors, in
particular A2A adenosine receptors, present anti-inflammatory action in acute and
chronic retinal inflammation. Regarding the A3 receptor, selective agonists like
N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine (CF101) have been used for
the treatment of inflammatory ophthalmic diseases such as dry eye and
uveoretinitis. Sideways, diverse stimuli (sensory stimulation, large intraocular
pressure increases) can produce a release of ATP from ocular sensory innervation
or after injury to ocular tissues. Then, ATP will activate purinergic P2
receptors present in sensory nerve endings, the iris, the ciliary body, or other
tissues surrounding the anterior chamber of the eye to produce
uveitis/endophthalmitis. In summary, adenosine and nucleotides can activate
receptors in ocular structures susceptible to suffer from inflammatory processes.
This involvement suggests the possible use of purinergic agonists and antagonists
as therapeutic targets for ocular inflammation.
PMID- 25132734
TI - Endocan levels in peripheral blood predict outcomes of acute respiratory distress
syndrome.
AB - PURPOSE: To investigate the prognostic significance of endocan, compared with
procalcitonin (PCT), C-reactive protein (CRP),white blood cells (WBC),
neutrophils (N), and clinical severity scores in patients with ARDS. METHODS: A
total of 42 patients with ARDS were initially enrolled, and there were 20
nonsurvivors and 22 survivors based on hospital mortality. Plasma levels of
biomarkers were measured and the acute physiology and chronic health evaluation
II (APACHE II) was calculated on day 1 after the patient met the defining
criteria of ARDS. RESULTS: Endocan levels significantly correlated with the
APACHE II score in the ARDS group (r = 0.676, P = 0.000, n = 42). Of 42
individuals with ARDS, 20 were dead, and endocan was significantly higher in
nonsurvivors than in survivors (median (IQR) 5.01 (2.98-8.44) versus 3.01 (2.36
4.36) ng/mL, P = 0.017). According to the results of the ROC-curve analysis and
COX proportional hazards models, endocan can predict mortality of ARDS
independently with a hazard ratio of 1.374 (95% CI, 1.150-1.641) and an area of
receiver operator characteristic curve (AUROC) of 0.715 (P = 0.017). Moreover,
endocan can predict the multiple-organ dysfunction of ARDS. CONCLUSION: Endocan
is a promising biomarker to predict the disease severity and mortality in
patients with ARDS.
PMID- 25132736
TI - Intestinal mucosal barrier is injured by BMP2/4 via activation of NF-kappaB
signals after ischemic reperfusion.
AB - Intestinal ischemic reperfusion (I/R) can cause dysfunction of the intestinal
mucosal barrier; however, the mechanism of the intestinal mucosal barrier
dysfunction caused by I/R remains unclear. In this study, using intestinal
epithelial cells under anaerobic cultivation and an in vivo rat intestinal I/R
model, we found that hypoxia and I/R increased the expression of BMP2/4 and
upregulated BMP type Ia receptor and BMP type II receptor expression. We also
found that exogenous BMP2/4 can activate the ERK and AKT signaling pathways in
rat small intestine (IEC-6) cells, thereby activating NF-kappaB signaling, which
leads to increased levels of inflammatory factors, such as TNF-alpha and IL-6.
Furthermore, recombinant BMP2/4 decreased the expression of the tight junction
protein occludin via the activation of the NF-kappaB pathway; these effects were
abolished by treatment with the BMP-specific antagonist noggin or the NF-kappaB
inhibitor pyrrolidine dithiocarbamate (PDTC). All these factors can destroy the
intestinal mucosal barrier, thereby leading to weaker barrier function. On the
basis of these data, we conclude that BMP2/4 may act as the pathogenic basis for
intestinal mucosal barrier dysfunction when the intestines suffer an I/R injury.
Our results provide background for the development pharmacologic interventions in
the management of I/R injury.
PMID- 25132738
TI - Diagnostics for Statistical Variable Selection Methods for Prediction of Peptic
Ulcer Disease in Helicobacter pylori Infection.
AB - BACKGROUND: The development of accurate classification models depends upon the
methods used to identify the most relevant variables. The aim of this article is
to evaluate variable selection methods to identify important variables in
predicting a binary response using nonlinear statistical models. Our goals in
model selection include producing non-overfitting stable models that are
interpretable, that generate accurate predictions and have minimum bias. This
work was motivated by data on clinical and laboratory features of Helicobacter
pylori infections obtained from 60 individuals enrolled in a prospective
observational study. RESULTS: We carried out a comprehensive performance
comparison of several nonlinear classification models over the H. pylori data
set. We compared variable selection results by Multivariate Adaptive Regression
Splines (MARS), Logistic Regression with regularization, Generalized Additive
Models (GAMs) and Bayesian Variable Selection in GAMs. We found that the MARS
model approach has the highest predictive power because the nonlinearity
assumptions of candidate predictors are strongly satisfied, a finding
demonstrated via deviance chi-square testing procedures in GAMs. CONCLUSIONS: Our
results suggest that the physiological free amino acids citrulline, histidine,
lysine and arginine are the major features for predicting H. pylori peptic ulcer
disease on the basis of amino acid profiling.
PMID- 25132733
TI - Role of microglia adenosine A(2A) receptors in retinal and brain
neurodegenerative diseases.
AB - Neuroinflammation mediated by microglial cells in the brain has been commonly
associated with neurodegenerative diseases. Whether this microglia-mediated
neuroinflammation is cause or consequence of neurodegeneration is still a matter
of controversy. However, it is unequivocal that chronic neuroinflammation plays a
role in disease progression and halting that process represents a potential
therapeutic strategy. The neuromodulator adenosine emerges as a promising
targeting candidate based on its ability to regulate microglial proliferation,
chemotaxis, and reactivity through the activation of its G protein coupled A2A
receptor (A2AR). This is in striking agreement with the ability of A2AR blockade
to control several brain diseases. Retinal degenerative diseases have been also
associated with microglia-mediated neuroinflammation, but the role of A2AR has
been scarcely explored. This review aims to compare inflammatory features of
Parkinson's and Alzheimer's diseases with glaucoma and diabetic retinopathy,
discussing the therapeutic potential of A2AR in these degenerative conditions.
PMID- 25132739
TI - Endoscopic ultrasound and paracentesis in the evaluation of small volume ascites
in patients with intra-abdominal malignancies.
AB - The evaluation of ascites in patients with known or suspected malignancy is a
critical aspect of preoperative staging. Endoscopic evaluation by ultrasound of
low volume ascites and sampling of the ascitic fluid by endoscopic ultrasound
guided paracentesis (EUS-P) is both a sensitive and specific modality for the
determination of peritoneal implants, which is not only an important prognostic
indicator but a crucial factor in determining treatment strategy. It is common
practice to utilize EUS for gastrointestinal malignancies such as pancreatic or
gastric masses, with the performance of paracentesis during the same procedure
for the purpose of imaging the abnormality and possibly performing fine needle
aspiration for biopsy of the neoplasm itself. However, given the ability of EUS-P
to adequately sample even minimal ascites, detecting much smaller volumes than
traditional computed tomography or magnetic resonance imaging, EUS-P may be a
useful modality for the standard metastatic workup of any newly diagnosed or
suspected malignancy. In this "Field of Vision" commentary, we discuss the role
of EUS-P, including the article by Suzuki et al reporting their experience with
EUS-P using an automated spring-loaded needle device. We also review the utility
of EUS-P for non-gastrointestinal malignancies, such as ovarian cancer, which has
a high incidence of malignant ascites.
PMID- 25132737
TI - Untangling the web of systemic autoinflammatory diseases.
AB - The innate immune system is involved in the pathophysiology of systemic
autoinflammatory diseases (SAIDs), an enlarging group of disorders caused by
dysregulated production of proinflammatory cytokines, such as interleukin-1beta
and tumor necrosis factor-alpha, in which autoreactive T-lymphocytes and
autoantibodies are indeed absent. A widely deranged innate immunity leads to
overactivity of proinflammatory cytokines and subsequent multisite inflammatory
symptoms depicting various conditions, such as hereditary periodic fevers,
granulomatous disorders, and pyogenic diseases, collectively described in this
review. Further research should enhance our understanding of the genetics behind
SAIDs, unearth triggers of inflammatory attacks, and result in improvement for
their diagnosis and treatment.
PMID- 25132740
TI - Current management of hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and
leading cause of death among patients with cirrhosis. Treatment guidelines are
based according to the Barcelona Clinic Liver Cancer staging system. The choice
among therapeutic options that include liver resection, liver transplantation,
locoregional, and systemic treatments must be individualized for each patient.
The aim of this paper is to review the outcomes that can be achieved in the
treatment of HCC with the heterogeneous therapeutic options currently available
in clinical practice.
PMID- 25132741
TI - Hepatitis B virus, HBx mutants and their role in hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is one of the leading causes of death induced by
cancer in the modern world and majority of the cases are related to chronic
hepatitis B virus (HBV) infection. HBV-encoded X protein (HBx) is known to play a
pivotal role in the pathogenesis of viral induced HCC. HBx is a multifunctional
protein of 17 kDa which modulates several cellular processes by direct or
indirect interaction with a repertoire of host factors resulting in HCC. HBX
might interfere with several cellular processes such as oxidative stress, DNA
repair, signal transduction, transcription, protein degradation, cell cycle
progression and apoptosis. A number of reports have indicated that HBx is one of
the most common viral ORFs that is often integrated into the host genome and its
sequence variants play a crucial role in HCC. By mutational or deletion analysis
it was shown that carboxy terminal of HBx has a likely role in protein-protein
interactions, transcriptional transactivation, DNA repair, cell, signaling and
pathogenesis of HCC. The accumulated evidence thus far suggests that it is
difficult to understand the mechanistic nature of HBx associated HCC, and HBx
mediated transcriptional transactivation and signaling pathways may be a major
determinant. This article addresses the role of HBx in the development of HCC
with particular emphasis on HBx mutants and their putative targets.
PMID- 25132742
TI - Implications of biomarkers in human hepatocellular carcinoma pathogenesis and
therapy.
AB - Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide and
accounts for approximately one-third of all malignancies. In the past decade,
advances have been made to improve the prognosis of HCC, including improvement in
the clinical diagnosis of early-stage HCC using molecular biomarkers and
molecular-targeted therapy to treat advanced HCC. However, the diagnosis,
pathogenesis and targeted therapy of HCC are not completely independent, and
should be comprehensively studied. For example, a number of tumor markers provide
useful clinical information not only for prognosis, but also in pathogenesis and
treatment efficacy. Therefore, this review will focus on the role of several
specific biomarkers implicated in the pathogenesis of HCC and several promising
molecular-targeted drugs that target the biomarkers of HCC.
PMID- 25132745
TI - Rationally designed treatment for metastatic colorectal cancer: current drug
development strategies.
AB - The therapeutic landscape of metastatic colorectal cancer (mCRC) has changed
substantially with the emergence of new molecularly targeted agents (MTA) used as
single agents or alongside standard chemotherapy. The use of these MTAs extended
the overall survival of patients with mCRC to a level that current
chemotherapeutics alone could not achieve. In addition, improvement in surgical
techniques and ablation modalities offer cure to a limited subset of patients
with mCRC and MTAs have been found to have a significant role here too, as they
aid resectability. However, for the majority of patients, mCRC remains an
invariably incurable disease necessitating continued courses of combined
treatment modalities. During the course of these treatments, either cytotoxic or
biological, cancer cells maintain their ability to acquire mitogenic mutations
which render them resistant to treatment. Key challenges remain to identify
appropriate subsets of patients who will most likely benefit from these new MTAs
and effectively select these based on validated biomarkers. Moreover, better
knowledge of the biology of colorectal cancer and the mechanisms via which it
bypasses blockade of known signalling pathways will help us design better and
more rational sequencing of these treatments, so that we can maximise the
survivorship of mCRC patients. This review outlines treatment strategies for
known molecular alterations with new MTAs and highlights some promising
strategies.
PMID- 25132744
TI - STAT3 and sphingosine-1-phosphate in inflammation-associated colorectal cancer.
AB - Accumulated evidences have demonstrated that signal transducer and activator of
transcription 3 (STAT3) is a critical link between inflammation and cancer.
Multiple studies have indicated that persistent activation of STAT3 in
epithelial/tumor cells in inflammation-associated colorectal cancer (CRC) is
associated with sphingosine-1-phosphate (S1P) receptor signaling. In inflammatory
response whereby interleukin (IL)-6 production is abundant, STAT3-mediated
pathways were found to promote the activation of sphingosine kinases (SphK1 and
SphK2) leading to the production of S1P. Reciprocally, S1P encourages the
activation of STAT3 through a positive autocrine-loop signaling. The crosstalk
between IL-6, STAT3 and sphingolipid regulated pathways may play an essential
role in tumorigenesis and tumor progression in inflamed intestines. Therapeutics
targeting both STAT3 and sphingolipid are therefore likely to contribute novel
and more effective therapeutic strategies against inflammation-associated CRC.
PMID- 25132743
TI - Inflammatory bowel disease in pediatric and adolescent patients: a biomolecular
and histopathological review.
AB - Crohn's disease (CD) and ulcerative colitis (UC) are the two main forms of
inflammatory bowel disease (IBD) with both overlapping and distinct clinical,
pathological and biomolecular features. It has been suggested that pediatric IBD
is a distinct disease entity, with probably different disease subtypes.The aim of
this study is to review and summarize the evolution of the current concept of
pediatric IBD. The results of this review reinforce the idea that pediatric CD
and UC may be further classified in various clinicopathologic entities. For
clinicians and pathologists convenience, practical algorithms for the distinction
of the various subphenotypes of pediatric IBD are also provided.
PMID- 25132746
TI - Prognostic relevance of minimal residual disease in colorectal cancer.
AB - Presence of occult minimal residual disease in patients with colorectal cancer
(CRC) has a strong prognostic impact on survival. Minimal residual disease plays
a major role in disease relapse and formation of metastases in CRC. Analysis of
circulating tumor cells (CTC) in the blood is increasingly used in clinical
practice for disease monitoring of CRC patients. In this review article the role
of CTC, disseminated tumor cells (DTC) in the bone marrow and micrometastases and
isolated tumor cells (ITC) in the lymph nodes will be discussed, including
literature published until September 2013. Occult disease is a strong prognostic
marker for patient survival in CRC and defined by the presence of CTC in the
blood, DTC in the bone marrow and/or micrometastases and ITC in the lymph nodes.
Minimal residual disease could be used in the future to identify patient groups
at risk, who might benefit from individualized treatment options.
PMID- 25132747
TI - Bowman-Birk inhibitors from legumes as colorectal chemopreventive agents.
AB - Aberrant functioning of serine proteases in inflammatory and carcinogenic
processes within the gastrointestinal tract (GIT) has prompted scientists to
investigate the potential of serine protease inhibitors, both natural and
synthetic, as modulators of their proteolytic activities. Protease inhibitors of
the Bowman-Birk type, a major protease inhibitor family in legume seeds, which
inhibit potently and specifically trypsin- and chymotrypsin-like proteases, are
currently being investigated as colorectal chemopreventive agents.
Physiologically relevant amounts of Bowman-Birk inhibitors (BBI) can reach the
large intestine in active form due to their extraordinary resistance to extreme
conditions within the GIT. Studies in animal models have proven that dietary BBI
from several legume sources, including soybean, pea, lentil and chickpea, can
prevent or suppress carcinogenic and inflammatory processes within the GIT.
Although the therapeutic targets and the action mechanism of BBI have not yet
been elucidated, the emerging evidence suggests that BBI exert their preventive
properties via protease inhibition; in this sense, serine proteases should be
considered as primary targets in early stages of carcinogenesis. The validation
of candidate serine proteases as therapeutic targets together with the
identification, within the wide array of natural BBI variants, of the most potent
and specific protease inhibitors, are necessary to better understand the
potential of this protein family as colorectal chemopreventive agents.
PMID- 25132749
TI - Helicobacter pylori infection and drugs malabsorption.
AB - Drug absorption represents an important factor affecting the efficacy of oral
drug treatment. Gastric secretion and motility seem to be critical for drug
absorption. A causal relationship between impaired absorption of orally
administered drugs and Helicobacter pylori (H. pylori) infection has been
proposed. Associations have been reported between poor bioavailability of l
thyroxine and l-dopa and H. pylori infection. According to the Maastricht
Florence Consensus Report on the management of H. pylori infection, H. pylori
treatment improves the bioavailability of both these drugs, whereas the direct
clinical benefits to patients still await to be established. Less strong seems
the association between H. pylori infection and other drugs malabsorption, such
as delavirdine and ketoconazole. The exact mechanisms forming the basis of the
relationship between H. pylori infection and impaired drugs absorption and/or
bioavailability are not fully elucidated. H. pylori infection may trigger a
chronic inflammation of the gastric mucosa, and impaired gastric acid secretion
often follows. The reduction of acid secretion closely relates with the wideness
and the severity of the damage and may affect drug absorption. This minireview
focuses on the evidence of H. pylori infection associated with impaired drug
absorption.
PMID- 25132748
TI - FOLFOX/FOLFIRI pharmacogenetics: the call for a personalized approach in
colorectal cancer therapy.
AB - While 5-fluorouracil used as single agent in patients with metastatic colorectal
cancer has an objective response rate around 20%, the administration of
combinations of irinotecan with 5-fluorouracil/folinic acid or oxaliplatin with 5
fluorouracil/folinic acid results in significantly increased response rates and
improved survival. However, the side effects of systemic therapy such as
myelotoxicity, neurotoxicity or gastrointestinal toxicity may lead to life
threatening complications and have a major impact on the quality of life of the
patients. Therefore, biomarkers that would be instrumental in the choice of
optimal type, combination and dose of drugs for an individual patient are
urgently needed. The efficacy and toxicity of anticancer drugs in tumor cells is
determined by the effective concentration in tumor cells, healthy tissues and by
the presence and quantity of the drug targets. Enzymes active in drug metabolism
and transport represent important determinants of the therapeutic outcome. The
aim of this review was to summarize published data on associations of gene and
protein expression, and genetic variability of putative biomarkers with response
to therapy of colorectal cancer to 5-fluorouracil/leucovorin/oxaliplatin and 5
fluorouracil/leukovorin/irinotecan regimens. Gaps in the knowledge identified by
this review may aid the design of future research and clinical trials.
PMID- 25132750
TI - Optimizing clarithromycin-containing therapy for Helicobacter pylori in the era
of antibiotic resistance.
AB - The efficacy of triple therapy for Helicobacter pylori infection has dramatically
declined over the last decade, largely related to increasing clarithromycin
resistance rates. From a microbiological standpoint, bismuth quadruple therapy is
the ideal replacement since it combines drugs for which resistance does not
impair its efficacy. Nonetheless, several obstacles such as availability,
complexity or tolerance prevent a general implementation of bismuth quadruple
therapy, so non-bismuth quadruple regimens remain the best first-line treatment
in clinical practice in many geographical areas. We review the rationale and
efficacy of several optimization tools (increasing the length of duration, high
dose acid suppression, probiotics), which have been largely evaluated over the
last 5 years to increase the effectiveness of standard triple therapy. Then, we
update available evidence on the effectiveness of several non-bismuth quadruple
therapies (sequential, concomitant, hybrid, miscellaneous therapy), which have
gained interest lately. We also revise evidence on the efficacy of the
aforementioned optimization tools for non-bismuth quadruples schemes and, finally
we provide a novel regionalized therapeutic algorithm, based on novel formulas
recently developed for predicting the outcome of non-bismuth quadruple regimens,
upon local antibiotic resistance rates.
PMID- 25132751
TI - Prevention of Helicobacter pylori infection in childhood.
AB - Helicobacter pylori (H. pylori) infection is one of the most common infections
worldwide. Although infection rates are falling in the developed and developing
countries, H. pylori is still widespread in the world. This article has reviewed
the important publications on H. pylori in childhood with a focus on its evolving
transmission route and the source of infection and preventive strategies in
childhood, PubMed was searched up to identify eligible studies. Relevant
publications were searched using the following.
PMID- 25132752
TI - Helicobacter pylori eradication in West Asia: a review.
AB - The efficacy of first- and second-line Helicobacter pylori (H. pylori)
eradication regimens varies considerably in West Asian countries, mainly due to
the variable prevalence of resistant organisms. However, no review article has
yet evaluated and compared the efficacy of different regimens among different
countries of this region. Therefore, we conducted a review to select the best
options and provide recommendations for H. pylori treatment in this geographic
region. A search through PubMed was carried out to obtain relevant randomized
clinical trials published in English language up to June 2013. According to the
results, among different therapeutic regimens used as the first-line protocols,
10-d Bismuth-Furazolidone/Metronidazole quadruple therapy, 14-d Clarithromycin
containing hybrid therapy and 14-d quadruple therapy including a proton pump
inhibitor + Bismuth + Tetracycline (500 mg QID) + Metronidazole (500 mg TDS)
seemed to be appropriate options. Among second-line therapeutic regimens, Bismuth
based quadruple therapies containing Tetracycline and Furazolidone/Metronidazole,
triple therapy containing Amoxicillin and Gatifloxacin and Quadruple therapy
including Bismuth + Azithromycin and Ofloxacin seemed to be effective options.
Third-line therapies were not evaluated in West Asia; most guidelines, however,
recommend choosing optimal eradication regimen according to the pattern of
antibiotic susceptibility of H. pylori. Although we limited our investigation to
H. pylori eradication regimens in West Asia, the clinical significance of the
results goes beyond the countries situated in this geographic region. In fact,
the results are transferrable to any region as long as the patterns of resistance
are the same.
PMID- 25132753
TI - Medicinal plant activity on Helicobacter pylori related diseases.
AB - More than 50% of the world population is infected with Helicobacter pylori (H.
pylori). The bacterium highly links to peptic ulcer diseases and duodenal ulcer,
which was classified as a group I carcinogen in 1994 by the WHO. The pathogenesis
of H. pylori is contributed by its virulence factors including urease, flagella,
vacuolating cytotoxin A (VacA), cytotoxin-associated gene antigen (Cag A), and
others. Of those virulence factors, VacA and CagA play the key roles. Infection
with H. pylori vacA-positive strains can lead to vacuolation and apoptosis,
whereas infection with cagA-positive strains might result in severe gastric
inflammation and gastric cancer. Numerous medicinal plants have been reported for
their anti-H. pylori activity, and the relevant active compounds including
polyphenols, flavonoids, quinones, coumarins, terpenoids, and alkaloids have been
studied. The anti-H. pylori action mechanisms, including inhibition of enzymatic
(urease, DNA gyrase, dihydrofolate reductase, N-acetyltransferase, and
myeloperoxidase) and adhesive activities, high redox potential, and
hydrophilic/hydrophobic natures of compounds, have also been discussed in detail.
H. pylori-induced gastric inflammation may progress to superficial gastritis,
atrophic gastritis, and finally gastric cancer. Many natural products have anti
H. pylori-induced inflammation activity and the relevant mechanisms include
suppression of nuclear factor-kappaB and mitogen-activated protein kinase pathway
activation and inhibition of oxidative stress. Anti-H. pylori induced gastric
inflammatory effects of plant products, including quercetin, apigenin,
carotenoids-rich algae, tea product, garlic extract, apple peel polyphenol, and
finger-root extract, have been documented. In conclusion, many medicinal plant
products possess anti-H. pylori activity as well as an anti-H. pylori-induced
gastric inflammatory effect. Those plant products have showed great potential as
pharmaceutical candidates for H. pylori eradication and H. pylori induced related
gastric disease prevention.
PMID- 25132755
TI - Natural history of chronic hepatitis B: phases in a complex relationship.
AB - Chronic hepatitis B (CHB) is a condition of global prevalence and its sequelae
include cirrhosis and hepatocellular carcinoma. The natural history of CHB is a
complex interplay of virological, environmental and host factors. The dynamic
relationship between the virus and host evolves over the duration of the
infection and different phases of the disease have been observed and described.
These have been conceptualized in terms of the state of balance between the host
immune system and the hepatitis B virus and have been given the labels immune
tolerant, immune clearance, immune control and immune escape although other
nomenclature is also used. Host factors, such as age at infection, determine
progression to chronicity. Virological factors including hepatitis B viral load,
mutations and genotype also have an impact on the adverse outcomes of the
infection, as do hepatotoxic cofactors such as alcohol. Our understanding of the
natural history of CHB has evolved significantly over the past few decades and
characterizing the phase of disease of CHB remains an integral part of managing
this virus in the clinic.
PMID- 25132754
TI - Hepatitis B vaccine by intradermal route in non responder patients: an update.
AB - Vaccination is the main prophylactic measure to reduce the mortality caused by
hepatitis B virus (HBV) infection in healthy subjects since the immune response
to hepatitis B recombinant vaccination occurs in over 90% of general population.
Individuals who develop an anti-HBs titer less than 10 mIU/mL after primary
vaccination cycle are defined "no responders". Many factors could cause a non
response to the HBV vaccination, such as administration of the vaccine in
buttocks, impaired vaccine storage conditions, drug abuse, smoking, infections
and obesity. Moreover there are some diseases, like chronic kidney disease, human
immunodeficiency virus infection, chronic liver disease, celiac disease,
thalassaemia, type I diabetes mellitus, down's syndrome and other forms of mental
retardation that are characterized by a poorer response to HBV vaccination than
healthy subjects. To date it is still unclear how to treat this group of patients
at high risk of hepatitis B infection. Recent studies seem to indicate that the
administration of HBV recombinant vaccine by the intradermal route is very
effective and could represent a more useful strategy than intramuscular route.
This review focuses on the use of anti hepatitis B vaccine by intradermal route
as alternative to conventional intramuscular vaccine in all non responder
patients. A comprehensive review of the literature using PubMed database, with
appropriate terms, was undertaken for articles in English published since 1983.
The literature search was undertaken in September 2013.
PMID- 25132757
TI - Proton pump inhibitor responsive esophageal eosinophilia, a distinct disease
entity?
AB - Recent studies have suggested the existence of a patient population with
esophageal eosinophilia that responds to proton pump inhibitor therapy. These
patients are being referred to as having proton pump inhibitor responsive
esophageal eosinophilia (PPI-REE), which is currently classified as a distinct
and separate disease entity from both gastroesophageal reflux disease (GERD) and
eosinophilic esophagitis (EoE). The therapeutic effect of proton pump inhibitor
(PPI) on PPI-REE is thought to act directly at the level of the esophageal mucosa
with an anti-inflammatory capacity, and completely independent of gastric acid
suppression. The purpose of this manuscript is to review the mechanistic data of
the proposed immune modulation/anti-inflammatory role of the PPI at the
esophageal mucosa, and the existence of PPI-REE as a distinct disease entity from
GERD and EoE.
PMID- 25132756
TI - Pancreatic cancer-improved care achievable.
AB - Pancreatic adenocarcinoma is one of the most aggressive cancers, and the decline
in mortality observed in most other cancer diseases, has so far not taken place
in pancreatic cancer. Complete tumor resection is a requirement for potential
cure, and the reorganization of care in the direction of high patient-volume
centers, offering multimodal treatment, has improved survival and Quality of
Life. Also the rates and severity grade of complications are improving in high
volume pancreatic centers. One of the major problems worldwide is
underutilization of surgery in resectable pancreatic cancer. Suboptimal
investigation, follow up and oncological treatment outside specialized centers
are additional key problems. New chemotherapeutic regimens like FOLFIRINOX have
improved survival in patients with metastatic disease, and different adjuvant
treatment options result in well documented survival benefit. Neoadjuvant
treatment is highly relevant, but needs further evaluation. Also adjuvant
immunotherapy, in the form of vaccination with synthetic K-Ras-peptides, has been
shown to produce long term immunological memory in cytotoxic T-cells in long term
survivors. Improvement in clinical outcome is already achievable and further
progress is expected in the near future for patients treated with curative as
well as palliative intention.
PMID- 25132758
TI - Personalizing medicine for metastatic colorectal cancer: current developments.
AB - Metastatic colorectal cancer (mCRC) is still one of the tumor types with the
highest incidence and mortality. In 2012, colorectal cancer was the second most
prevalence cancer among males (9%) and the third among females (8%). In this
disease, early diagnosis is important to improve treatment outcomes. However, at
the time of diagnosis, about one quarter of patients already have metastases, and
overall survival of these patients at 5-years survival is very low. Because of
these poor statistics, the development of new drugs against specific targets,
including the pathway of angiogenesis, has witnessed a remarkable increase. So,
targets therapies through epidermal growth factor and its receptor and also KRAS
pathways modulation acquired a main role whether in association with standard
chemotherapy and radiotherapy. With the current knowledge in the field of
molecular biology, including genetic mutations and polymorphisms, we know better
why patients respond so differently to the same treatments. So, in the future we
can develop increasingly personalized treatments to the patient and not the
disease. This review aims to summarize some molecular pathways and their relation
to tumor growth, as well as novel targeted developing drugs and recently approved
for mCRC.
PMID- 25132759
TI - MiRNA as potential biomarkers and therapeutic targets for gastric cancer.
AB - Gastric cancer is one of the leading causes of cancer mortality in the world.
Aberrant expression of microRNAs (miRNAs) is the hallmark of this disease. MiRNAs
are endogenous non-coding RNAs that are involved in many biological processes
(e.g., cell proliferation, differentiation, apoptosis, invasion and development)
through gene repression. Deregulation of miRNA expression in gastric tumors and
cancer cell lines have been documented to contribute in tumorigenesis, and the
expression signature may correlate with different cancer types and
clinicopathological features. Here, we summarized the updated gastric cancer
associated miRNAs and the downstream targets in the process of tumorigenesis.
Recently, many researchers make use of the miRNA microarray platform to profile
miRNA expression in gastric cancer and correlated with different clinical
parameters. Its application on cancer diagnosis, prognosis and predicting
treatment response rate are still underway and needs further investigation.
Emerging roles of miRNAs with oncogenic or tumor suppressive properties in
gastric tumorigenesis were discussed. Epigenetic silencing of miRNA by
hypermethylation of promoter CpG island was also observed in gastric cancer.
However, detailed mechanisms of how miRNAs regulate gene expression in gastric
cancer has not been well studied. In this review, we highlight the up-to-date
findings on the deregulated miRNAs in gastric cancer, and the potential use of
miRNA in the clinical settings, such as diagnostic/prognostic markers and
chemotherapeutic tools.
PMID- 25132760
TI - Osteopontin knockdown suppresses the growth and angiogenesis of colon cancer
cells.
AB - AIM: To investigate the effects of osteopontin (OPN) gene expression knockdown on
colon cancer Lovo cells in vitro. METHODS: Four candidate small interfering RNA
(siRNA) constructs targeting the OPN gene and a scrambled control sequence (NC
siRNA) were synthesized and inserted into a pGPU6/GFP/Neo expression vector.
After confirmation by restriction enzyme digestion and DNA sequencing, the
recombinant plasmids were subsequently transfected into a human colon cancer cell
line (Lovo) using a liposome transfection method. Stably transfected cells were
maintained with G418 selection and referred to as Lovo-OPN-1, -2, -3, -4, and
Lovo-NC cells. Knockdown efficiency of each of the four siRNA constructs was
determined by real-time reverse transcription polymerase chain reaction assays
and western blotting, and the construct with the most effective silencing was
used for subsequent experiments. Cell proliferation, adhesion, and Matrigel
invasion assays were performed to analyze the effects of OPN knockdown in stably
transfected Lovo cells. The levels of four angiogenic factors, namely vascular
endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, MMP-9 and
urokinase plasminogen activator were detected by enzyme-linked immunosorbent
assays (ELISA). RESULTS: Recombinant vectors containing OPN-specific and
scrambled siRNA sequences were successfully constructed and stably transfected
into Lovo cells. Compared with the control Lovo and Lovo-NC cells, the levels of
OPN mRNA and protein expression in Lovo-OPN-1, -2, -3, and -4 were significantly
reduced (all P < 0.05), with the most efficient reduction observed in Lovo-OPN-4
cells (P < 0.05). Relative to untransfected Lovo cells, OPN mRNA expression
levels in Lovo-NC and Lovo-OPN-4 cells were 1.008 +/- 0.067 and 0.160 +/- 0.023,
respectively. The relative OPN protein expression levels in Lovo, Lovo-NC, and
Lovo-OPN-4 cells were 3.024 +/- 0.211, 2.974 +/- 0.630, and 0.121 +/- 0.008,
respectively. Moreover, transfection with the scrambled sequence had no effect on
the expression of OPN. After 24, 48, 72, and 96 h of cultivation, absorption
values at 450 nm to assess proliferation of Lovo-OPN-4 cells were 0.210 +/-
0.017, 0.247 +/- 0.024, 0.314 +/- 0.037, and 0.359 +/- 0.043, respectively, which
were significantly lower than those of Lovo (0.244 +/- 0.031, 0.313 +/- 0.024,
0.513 +/- 0.048 and 0.783 +/- 0.051) and Lovo-NC cells (0.241 +/- 0.029, 0.309 +/
0.022, 0.563 +/- 0.023, and 0.735 +/- 0.067) (all P < 0.05). The absorption
values at 595 nm, which were measured in a cell adhesion assay, showed that
adhesion of Lovo-OPN-4 cells (0.215 +/- 0.036) was significantly decreased
compared to Lovo (0.490 +/- 0.037) and Lovo-NC cells (0.462 +/- 0.043) (P <
0.05). The number of invasive Lovo-OPN-4 cells (16.1 +/- 1.9) was also
significantly decreased compared to Lovo (49.9 +/- 5.4) and Lovo-NC cells (48.8
+/- 4.5) (P < 0.05). ELISA assays showed significant reductions in Lovo-OPN-4
cells compared to Lovo and Lovo-NC cells with regard to the expression of VEGF
(1687.85 +/- 167.84 ng/L vs 2348.54 +/- 143.80 ng/L and 2284.39 +/- 138.62 ng/L,
respectively), MMP-2 (2966.07 +/- 177.36 MUg/L vs 4084.74 +/- 349.54 MUg/L and
4011.41 +/- 424.48 MUg/L, respectively), MMP-9 (3782.89 +/- 300.64 MUg/L vs
5062.90 +/- 303.02 MUg/L and 4986.38 +/- 300.75 MUg/L, respectively) and uPA
(1152.69 +/- 120.79 MUg/L vs 1380.90 +/- 147.25 MUg/L and 1449.80 +/- 189.92
MUg/L, respectively) (all P < 0.05). CONCLUSION: Knockdown of OPN gene expression
suppresses colon cancer cell growth, adherence, invasion, and expression of
angiogenic factors.
PMID- 25132761
TI - Insulin resistance, adipokine profile and hepatic expression of SOCS-3 gene in
chronic hepatitis C.
AB - AIM: To analyze adipokine concentrations, insulin resistance and hepatic
expression of suppressor of cytokine signaling 3 (SOCS-3) in patients with
chronic hepatitis C genotype 1 with normal body weight, glucose and lipid
profile. METHODS: The study group consisted of 31 patients with chronic hepatitis
C and 9 healthy subjects. Total levels of adiponectin, leptin, resistin,
visfatin, omentin, osteopontin and insulin were measured using an ELISA kit. The
hepatic expression of SOCS-3 was determined by the use of the reverse
transcription polymerase chain reaction method. RESULTS: Homeostasis model
assessment for insulin resistance (HOMA-IR) values were significantly higher in
hepatitis C virus (HCV) infected patients without metabolic disorders compared to
healthy controls (2.24 vs 0.59, P = 0.0003). Hepatic steatosis was observed in
32.2% of patients with HCV infection and was found in patients with increased
HOMA-IR index (2.81 vs 1.99, P = 0.05) and reduced adiponectin level (5.96 vs
8.37, P = 0.04). Inflammatory activity (G >= 2) was related to increased
osteopontin concentration (34.04 vs 23.35, P = 0.03). Advanced liver fibrosis (S
>= 2) was associated with increased levels of omentin and osteopontin (436.94 vs
360.09, P = 0.03 and 32.84 vs 20.29, P = 0.03) and reduced resistin concentration
(1.40 vs 1.74, P = 0.047). No correlations were reported between adipokine
profile, HOMA-IR values and hepatic expression of the SOCS-3 gene. CONCLUSION: We
speculated that no relationship between adipokines and HOMA-IR values may
indicate that HCV can induce insulin resistance itself. Some adipokines appear to
be biochemical markers of steatosis, inflammation and fibrosis in patients with
chronic HCV infection. (c) 2014 Baishideng Publishing Group Inc. All rights
reserved.
PMID- 25132762
TI - Caspase-1 inhibition alleviates acute renal injury in rats with severe acute
pancreatitis.
AB - AIM: To assess the effect of inhibition of caspase-1 on acute renal injury in
rats with severe acute pancreatitis (SAP). METHODS: Forty-two Sprague-Dawley rats
were randomly divided into three groups: healthy controls (HC, n = 6), SAP rats
treated with saline (SAP-S, n = 18), or SAP rats treated with a caspase
1/interleukin (IL)-1beta-converting-enzyme (ICE) inhibitor (SAP-I-ICE, n = 18).
SAP was induced by retrograde infusion of 5% sodium taurocholate into the bile
pancreatic duct. HC rats were subjected to identical treatment and surgical
procedures without sodium taurocholate. Rats received an intraperitoneal
injection of isotonic saline (SAP-S) or the inhibitor (SAP-ICE-I) at 2 and 12 h
after induction of acute pancreatitis. Surviving rats were sacrificed at
different time points after SAP induction; all samples were obtained and stored
for subsequent analyses. The levels of blood urea nitrogen (BUN) and creatinine
(Cr) were measured using automatic methods, and serum IL-1beta concentrations
were measured by an enzyme-linked immunosorbent assay. Intrarenal expression of
IL-1beta, IL-18 and caspase-1 mRNAs was detected by RT-PCR. IL-1beta protein
expression and the pathologic changes in kidney tissues were observed by
microscopy after immunohistochemical or hematoxylin and eosin staining,
respectively. RESULTS: The serum levels of BUN and Cr in the SAP-S group were
12.48 +/- 2.30 mmol/L and 82.83 +/- 13.89 MUmol/L at 6 h, 23.53 +/- 2.58 mmol/L
and 123.67 +/- 17.67 MUmol/L at 12 h, and 23.60 +/- 3.33 mmol/L and 125.33 +/-
21.09 MUmol/L at 18 h, respectively. All were significantly increased compared to
HC rats (P < 0.01 for all). Levels in SAP-ICE-I rats were significantly decreased
compared to SAP-S rats both at 12 and 18 h (P < 0.01 for all). Serum IL-1beta
levels in the SAP-S group were 276.77 +/- 44.92 pg/mL at 6 h, 308.99 +/- 34.95
pg/mL at 12 h, and 311.60 +/- 46.51 pg/mL at 18 h; all significantly higher than
those in the HC and SAP-ICE-I groups (P < 0.01 for all). Intrarenal expression of
IL-1beta mRNA was weak in HC rats, but increased significantly in SAP-S rats (P <
0.01). ICE inhibition significantly decreased the expression of IL-1beta and IL
18 mRNAs (P < 0.05 for all vs SAP-S), whereas caspase-1 mRNA expression was not
significantly different. Weak IL-1beta immunostaining was observed in HC animals,
and marked staining was found in the SAP-S group mainly in renal tubular
epithelial cells. IL-1beta immunostaining was significantly descended in SAP-ICE
I rats compared to SAP-S rats (P < 0.05). Caspase-1 inhibition had no effect on
the severity of kidney tissue destruction. CONCLUSION: The expression of caspase
1-activated cytokines IL-1beta and IL-18 plays a pivotal role in acute renal
injury in rats with experimental SAP. Caspase-1 inhibition improves renal
function effectively.
PMID- 25132763
TI - Cost-effectiveness analysis of beta-blockers vs endoscopic surveillance in
patients with cirrhosis and small varices.
AB - AIM: To evaluate the most cost-effectiveness strategy for preventing variceal
growth and bleeding in patients with cirrhosis and small esophageal varices.
METHODS: A stochastic analysis based on decision trees was performed to compare
the cost-effectiveness of beta-blockers therapy starting from a diagnosis of
small varices (Strategy 1) with that of endoscopic surveillance followed by beta
blockers treatment when large varices are demonstrated (Strategy 2), for
preventing variceal growth, bleeding and death in patients with cirrhosis and
small esophageal varices. The basic nodes of the tree were gastrointestinal
endoscopy, inpatient admission and treatment for bleeding, as required. All
estimates were performed using a Monte Carlo microsimulation technique,
consisting in simulating observations from known probability distributions
depicted in the model. Eight-hundred-thousand simulations were performed to
obtain the final estimates. All estimates were then subjected to Monte Carlo
Probabilistic sensitivity analysis, to assess the impact of the variability of
such estimates on the outcome distributions. RESULTS: The event rate (considered
as progression of varices or bleeding or death) in Strategy 1 [24.09% (95%CI:
14.89%-33.29%)] was significantly lower than in Strategy 2 [60.00% (95%CI: 48.91%
71.08%)]. The mean cost (up to the first event) associated with Strategy 1 [823 L
(95%CI: 106 L-2036 L)] was not significantly different from that of Strategy 2
[799 L (95%CI: 0 L-3498 L)]. The cost-effectiveness ratio with respect to this
endpoint was equal to 50.26 L (95%CI: -504.37 L-604.89 L) per event avoided over
the four-year follow-up. When bleeding episodes/deaths in subjects whose varices
had grown were included, the mean cost associated with Strategy 1 was 1028 L
(95%CI: 122 L-2581 L), while 1699 L (95%CI: 171 L-4674 L) in Strategy 2.
CONCLUSION: Beta-blocker therapy turn out to be more effective and less expensive
than endoscopic surveillance for primary prophylaxis of bleeding in patients with
cirrhosis and small varices.
PMID- 25132764
TI - Diagnostic accuracy of endoscopic ultrasonography for rectal neuroendocrine
neoplasms.
AB - AIM: To investigate the diagnostic accuracy of endoscopic ultrasonography (EUS)
for rectal neuroendocrine neoplasms (NENs) and the differential diagnosis of
rectal NENs from other subepithelial lesions (SELs). METHODS: The study group
consisted of 36 consecutive patients with rectal NENs histopathologically
diagnosed using biopsy and/or resected specimens. The control group consisted of
31 patients with homochronous rectal non-NEN SELs confirmed by pathology.
Epithelial lesions such as cancer and adenoma were excluded from this study. One
EUS expert blinded to the histological results reviewed the ultrasonic images.
The size, original layer, echoic intensity and homogeneity of the lesions and the
perifocal structures were investigated. The single EUS diagnosis recorded by the
EUS expert was compared with the histological results. RESULTS: All NENs were
located at the rectum 2-10 cm from the anus and appeared as nodular (n = 12),
round (n = 19) or egg-shaped (n = 5) lesions with a hypoechoic (n = 7) or
intermediate (n = 29) echo pattern and a distinct border. Tumors ranged in size
from 2.3 to 13.7 mm, with an average size of 6.8 mm. Homogeneous echogenicity was
seen in all tumors except three. Apart from three patients (stage T2 in two and
stage T3 in one), the tumors were located in the second and/or third wall layer
without involvement of the fourth and fifth layers. In the patients with stage T1
disease, the tumors were located in the second wall layer only in seven cases,
the third wall layer only in two cases, and both the second and third wall layers
in 27 cases. Approximately 94.4% (34/36) of rectal NENs were diagnosed correctly
by EUS, and 74.2% (23/31) of other rectal SELs were classified correctly as non
NENs. Eight cases of other SELs were misdiagnosed as NENs, including two cases of
inflammatory lesions and one case each of gastrointestinal tumor, endometriosis,
metastatic tumor, lymphoma, neurilemmoma, and hemangioma. The positive predictive
value of EUS for rectal NENs was 80.9% (34/42), the negative predictive value was
92.0% (23/25), and the diagnostic accuracy was 85.1%. CONCLUSION: EUS has
satisfactory diagnostic accuracy for rectal NENs with good sensitivity, but
unfavorable specificity, making the differential diagnosis of NENs from other
SELs challenging.
PMID- 25132765
TI - Comparision of modified and conventional delta-shaped gastroduodenostomy in
totally laparoscopic surgery.
AB - AIM: To evaluate the safety and feasibility of a modified delta-shaped
gastroduodenostomy (DSG) in totally laparoscopic distal gastrectomy (TLDG).
METHODS: We performed a case-control study enrolling 63 patients with distal
gastric cancer (GC) undergoing TLDG with a DSG from January 2013 to June 2013.
Twenty-two patients underwent a conventional DSG (Con-Group), whereas the other
41 patients underwent a modified version of the DSG (Mod-Group). The modified
procedure required only the instruments of the surgeon and assistant to complete
the involution of the common stab incision and to completely resect the duodenal
cutting edge, resulting in an anastomosis with an inverted T-shaped appearance.
The clinicopathological characteristics, surgical outcomes, anastomosis time and
complications of the two groups were retrospectively analyzed using a
prospectively maintained comprehensive database. RESULTS: DSG procedures were
successfully completed in all of the patients with histologically complete (R0)
resections, and none of these patients required conversion to open surgery. The
clinicopathological characteristics of the two groups were similar. There were no
significant differences between the groups in the operative time, intraoperative
blood loss, extension of the lymph node (LN) dissection and number of dissected
LNs (150.8 +/- 21.6 min vs 143.4 +/- 23.4 min, P = 0.225 for the operative time;
26.8 +/- 11.3 min vs 30.6 +/- 14.8 mL, P = 0.157 for the intraoperative blood
loss; 4/18 vs 3/38, P = 0.375 for the extension of the LN dissection; and 43.9 +/
13.4 vs 39.5 +/- 11.5 per case, P = 0.151 for the number of dissected LNs). The
anastomosis time, however, was significantly shorter in the Mod-Group than in the
Con-Group (13.9 +/- 2.8 min vs 23.9 +/- 5.6 min, P = 0.000). The postoperative
outcomes, including the times to out-of-bed activities, first flatus, resumption
of soft diet and postoperative hospital stay, as well as the anastomosis size,
did not differ significantly (1.9 +/- 0.6 d vs 2.3 +/- 1.5 d, P = 0.228 for the
time to out-of-bed activities; 3.2 +/- 0.9 d vs 3.5 +/- 1.3 d, P = 0.295 for the
first flatus time; 7.5 +/- 0.8 d vs 8.1 +/- 4.3 d, P = 0.489 for the resumption
of a soft diet time; 14.3 +/- 10.6 d vs 11.5 +/- 4.9 d, P = 0.148 for the
postoperative hospital stay; and 30.5 +/- 3.6 mm vs 30.1 +/- 4.0 mm, P = 0.730
for the anastomosis size). One patient with minor anastomotic leakage in the Con
Group was managed conservatively; no other patients experienced any complications
around the anastomosis. The operative complication rates were similar in the Con-
and Mod-Groups (9.1% vs 7.3%, P = 1.000). CONCLUSION: The modified DSG, an
alternative reconstruction in TLDG for GC, is technically safe and feasible, with
a simpler process that reduces the anastomosis time.
PMID- 25132766
TI - Clinical epidemiology of gastric cancer in Hehuang valley of China: a 10-year
epidemiological study of gastric cancer.
AB - AIM: To investigate the clinical epidemiological characteristics of gastric
cancer in the Hehuang valley, China, to provide a reference for treatment and
prevention of regional gastric cancer. METHODS: Between February 2003 and
February 2013, the records of 2419 patients with gastric cancer were included in
this study. The patient's characteristics, histological and pathological
features, as well as the dietary habits of the patients, were investigated.
RESULTS: The clinical data showed that adenocarcinoma was the leading
histological type of gastric cancer in this area. Characteristics of gastric
cancer in different ethnic groups and age showed that the 60.55-65.50 years group
showed the high incidence of gastric cancer in all ethnic groups. There were more
male gastric cancer patients than female. Intestinal was the most common type of
gastric cancer in the Hehuang valley. There was no significant difference in the
proportion of sex in terms of Helicobacter pylori infection. The impact of
dietary habits on gastric cancer showed that regular consumption of fried or
grilled food, consumption of high-salt, high-fat and spicy food and drinking
strong Boiled brick-tea were three important factors associated with gastric
cancer in males and females. CONCLUSION: Differences existed in race, sex, and
age of patients according to the epidemiology of gastric cancer in the Hehuang
valley. Moreover, dietary habits was also an important factor contributing to
gastric cancer.
PMID- 25132767
TI - Comparative analysis of ERCP, IDUS, EUS and CT in predicting malignant bile duct
strictures.
AB - AIM: To compare endoscopic retrograde cholangio-pancreatography (ERCP),
intraductal ultrasound (IDUS), endosonography (EUS), endoscopic transpapillary
forceps biopsies (ETP) and computed tomography (CT) with respect to diagnosing
malignant bile duct strictures. METHODS: A patient cohort with bile duct
strictures of unknown etiology was examined by ERCP and IDUS, ETP, EUS, and CT.
The sensitivity, specificity, and accuracy rates of the diagnostic procedures
were calculated based on the definite diagnoses proved by histopathology or long
term follow-up in those patients who did not undergo surgery. For each of the
diagnostic measures, the sensitivity, specificity, and accuracy rates were
calculated. In all cases, the gold standard was the histopathologic staging of
specimens or long-term follow-up of at least 12 mo. A comparison of the accuracy
rates between the localization of strictures was performed by using the Mann
Whitney U-test and the chi(2) test as appropriate. A comparison of the accuracy
rates between the diagnostic procedures was performed by using the McNemar's
test. Differences were considered statistically significant if P < 0.05. RESULTS:
A total of 234 patients (127 males, 107 females, median age 64, range 20-90
years) with indeterminate bile duct strictures were included. A total of 161
patients underwent operative exploration; thus, a surgical histopathological
correlation was available for those patients. A total of 113 patients had
malignant disease proven by surgery; in 48 patients, benign disease was
surgically found. In these patients, the decision for surgical exploration was
made due to the suspicion of malignant disease in multimodal diagnostics (ERCP,
CT, or EUS). Fifty patients had a benign diagnosis and were followed by a
surveillance protocol with a follow-up of at least 12 mo; the median follow-up
was 34 mo. Twenty-three patients had extended malignant disease, and thus were
considered palliative. A comparison of the different diagnostic tools for
detecting bile duct malignancy resulted in accuracy rates of 91% (ERCP/IDUS), 59%
(ETP), 92% (IDUS + ETP), 74% (EUS), and 73% (CT), respectively. In the subgroup
analysis, the accuracy rates (%, ERCP + IDUS/ETP/IDUS + ETP; EUS; CT) for each
tumor entity were as follows: cholangiocellular carcinoma: 92%/74%/92%/70%/79%;
pancreatic carcinoma: 90%/68%/90%/81%/76%; and ampullary carcinoma:
88%/90%/90%/76%/76%. The detection rate of malignancy by ERCP/IDUS was superior
to ETP (91% vs 59%, P < 0.0001), EUS (91% vs 74%, P < 0.0001) and CT (91% vs 73%,
P < 0.0001); EUS was comparable to CT (74% vs 73%, P = 0.649). When analyzing
accuracy rates with regard to localization of the bile duct stenosis, the
accuracy rate of EUS for proximal vs distal stenosis was significantly higher for
distal stenosis (79% vs 57%, P < 0.0001). CONCLUSION: ERCP/IDUS is superior to
EUS and CT in providing accurate diagnoses of bile duct strictures of uncertain
etiology. Multimodal diagnostics is recommended.
PMID- 25132768
TI - One fifth of hospitalizations for peptic ulcer-related bleeding are potentially
preventable.
AB - AIM: To calculate the proportion of potentially preventable hospitalizations due
to peptic ulcer disease (PUD), erosive gastritis (EG) or duodenitis (ED).
METHODS: Retrospective cohort study using ICD-10 codes to identify all patients
with upper gastrointestinal hemorrhage secondary to endoscopically proven PUD, EG
or ED during the period from March 2007 to October 2010 in three major
metropolitan hospitals in Melbourne, Australia. Patients were divided into "high
risk" (those who would benefit from gastroprotection) and "not high risk" groups
as defined by established guidelines. Mean Rockall score, transfusion
requirement, length of stay, rebleeding rates, need for surgery and in-hospital
mortality was compared between "high risk" and "not high risk" groups. Within the
"high risk" group, those on gastroprotection and those with no gastroprotection
were also compared. RESULTS: Five hundred and seven patients were included for
analysis of which 174 were classified as high risk. Median values of complete
Rockall Score (5 vs 4, P = 0.002) and length of stay (5 d vs 4 d, P = 0.04) were
higher in the high risk group but in-hospital mortality was lower (0.6% vs 3.9%,
P = 0.03). 130 out of the 174 patients in the high risk group were not taking
recommended gastroprotective therapy prior to hospitalization. Past history of
PUD (OR = 3.7, P = 0.006) and clopidogrel use (OR = 3.2, P = 0.007) significantly
predicted prescription of gastroprotective therapy. Using proton pump inhibitor
protection rates of 50%-85% from published studies, an estimation of 13% to 22%
of the total number of the hospitalizations due to PUD or EG/ED related bleeding
may have been preventable. CONCLUSION: Up to one fifth of all hospitalizations
for bleeding secondary to PUD or EG/ED are potentially preventable.
PMID- 25132769
TI - Phenol-based endoscopic ultrasound-guided celiac plexus neurolysis for East Asian
alcohol-intolerant upper gastrointestinal cancer patients: a pilot study.
AB - AIM: To investigate the effectiveness of phenol for the relief of cancer pain by
endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN). METHODS: Twenty
two patients referred to our hospital with cancer pain from August 2009 to July
2011 for EUS-CPN were enrolled in this study. Phenol was used for 6 patients with
alcohol intolerance and ethanol was used for 16 patients without alcohol
intolerance. The primary endpoint was the positive response rate (pain score
decreased to <= 3) on postoperative day 7. Secondary endpoints included the time
to onset of pain relief, duration of pain relief, and complication rates.
RESULTS: There was no significant difference in the positive response rate on day
7. The rates were 83% and 69% in the phenol and ethanol groups, respectively.
Regarding the time to onset of pain relief, in the phenol group, the median pre
treatment pain score was 5, whereas the post-treatment scores decreased to 1.5,
1.5, and 1.5 at 2, 8, and 24 h, respectively (P < 0.05). In the ethanol group,
the median pre-treatment pain score was 5.5, whereas the post-treatment scores
significantly decreased to 2.5, 2.5, and 2.5 at 2, 8, and 24 h, respectively (P <
0.01). There was no significant difference in the duration of pain relief between
the phenol and ethanol groups. No significant difference was found in the rate of
complications between the 2 groups; however, burning pain and inebriation
occurred only in the ethanol group. CONCLUSION: Phenol had similar pain-relieving
effects to ethanol in EUS-CPN. Comparing the incidences of inebriation and
burning pain, phenol may be superior to ethanol in EUS-CPN procedures.
PMID- 25132770
TI - Length of negative resection margin does not affect local recurrence and survival
in the patients with gastric cancer.
AB - AIM: To investigate the influence of the resection margin on local recurrence and
survival in gastric cancer patients. METHODS: We reviewed the medical records of
1788 patients who had undergone gastrectomy for gastric cancer at the Seoul
National University Bundang Hospital, South Korea, between May 2003 and July
2009. The patients were divided into early and advanced gastric cancer groups. In
each group, we analyzed the relationship between clinicopathologic factors and
survival outcomes, and compared the hazard rates of event occurrence between
patients with resection margins above and below the cut-off value, using a Cox
proportional hazard model. RESULTS: The early and advanced gastric cancer groups
included 1001 and 787 patients, respectively. The hazard rates of event
occurrence did not significantly differ between the patients with resection
margins above the cut-off value and those with resection margins below the cut
off value (P > 0.05, in all comparisons). Based on the multivariable analyses,
the proximal and distal resection margins were not significantly associated with
survival outcomes and local recurrence (P > 0.05, in all analyses). CONCLUSION:
The proximal or distal resection margins did not affect the prognosis of patients
with gastric cancer if the margins were pathologically negative.
PMID- 25132771
TI - Refeeding syndrome in Southeastern Taiwan: our experience with 11 cases.
AB - AIM: To present our experience with refeeding syndrome in southeastern Taiwan.
METHODS: We conducted a retrospective study during a 2-year period at the Mackay
Memorial Hospital, Taitung Branch. We enrolled patients with very little or no
nutrition intake for more than 10 d, a high risk group of refeeding syndrome,
including those suffering from alcohol abuse, cancerous cachexia, chronic
malnutrition, and prolonged starvation. RESULTS: A total of 11 patients (7 males,
4 females) with nasogastric feeding were included as having refeeding syndrome.
Most of them had the symptoms of diarrhea, lethargy, and leg edema. The initial
nutritional supplement was found to be relatively high in calories (1355.1 +/-
296.2 kcal/d), high in protein (47.3 +/- 10.4 gm/d), low in vitamin B1 (2.0 +/-
0.5 mg/d), low in potassium (1260.4 +/- 297.7 mg/d), and low in phosphorus (660.1
+/- 151.8 mg/d). Furthermore, hypophosphatemia (2.4 +/- 0.9 mg/dL) was noted
during follow-up. Based on the suggestions of a dietician and a
gastroenterologist, the clinical disorders of diarrhea, malaise and leg edema
were significantly improved. The level of phosphate was also increased (3.3 +/-
0.6 mg/dL). CONCLUSION: Refeeding syndrome is an overlooked and risky disorder
that has some potentially fatal complications. Nasogastric feeding in nursing
homes is an important risk factor for patients and deserves greater attention
based on the initial results of this study.
PMID- 25132772
TI - Techniques and feasibility of laparoscopic extended right hemicolectomy with D3
lymphadenectomy.
AB - AIM: To illustrate the critical techniques and feasibility of laparoscopic
extended right hemicolectomy (LERH), according to our previous experience.
METHODS: Anatomical relationship and operative techniques were demonstrated. One
hundred and five consecutive patients who underwent extended right hemicolectomy
with D3 lymphadenectomy between January 2008 and May 2011 were included in the
present study [laparoscopic group (n = 48) vs open group (n = 57)]. RESULTS: The
right retrocolic space was the main surgical plan of the LERH. The superior
mesenteric vein was the most important anatomical landmark for vascular
dissection. The medial-to-lateral dissection approach made the LERH performed
efficiently. Compared with the open group, the LERH group had less blood loss
(111.7 +/- 127.8 mL vs 170.2 +/- 49.7 mL, P = 0.023), faster return of flatus
(3.0 +/- 1.6 d vs 3.7 +/- 1.3 d, P = 0.019), and earlier diet (4.2 +/- 1.4 d vs
5.0 +/- 1.2 d, P = 0.005). Five patients (10.4%) underwent conversion during
laparoscopic surgery. The cancer recurrence rates between the two groups were
comparable (laparoscopic vs open, 8.6% vs 9.1%, P = 0.335). CONCLUSION: For an
advanced tumor located at the hepatic flexure or proximal transverse colon, LERH
with D3 lymphadenectomy using a medial-to-lateral approach seems to be safe and
feasible when the superior mesenteric vein serves as the main anatomical landmark
and the right retrocolic space severed as the surgical plan.
PMID- 25132773
TI - Prognostic nutritional index predicts postoperative complications and long-term
outcomes of gastric cancer.
AB - AIM: To investigate the impact of prognostic nutritional index (PNI) on the
postoperative complications and long-term outcomes in gastric cancer patients
undergoing total gastrectomy. METHODS: The data for 386 patients with gastric
cancer were extracted and analyzed between January 2003 and December 2008 in our
center. The patients were divided into two groups according to the cutoff value
of the PNI: those with a PNI >= 46 and those with a PNI < 46. Clinicopathological
features were compared between the two groups and potential prognostic factors
were analyzed. The relationship between postoperative complications and PNI was
analyzed by logistic regression. The univariate and multivariate hazard ratios
were calculated using the Cox proportional hazard model. RESULTS: The optimal
cutoff value of the PNI was set at 46, and patients with a PNI >= 46 and those
with a PNI < 46 were classified into PNI-high and PNI-low groups, respectively.
Patients in the PNI-low group were more likely to have advanced tumor (T), node
(N), and TNM stages than patients in the PNI-high group. The low PNI is an
independent risk factor for the incidence of postoperative complications (OR =
2.223). The 5-year overall survival (OS) rates were 54.1% and 21.1% for patients
with a PNI >= 46 and those with a PNI < 46, respectively. The OS rates were
significantly lower in the PNI-low group than in the PNI-high group among
patients with stages II (P = 0.001) and III (P < 0.001) disease. CONCLUSION: The
PNI is a simple and useful marker not only to identify patients at increased risk
for postoperative complications, but also to predict long-term survival after
total gastrectomy. The PNI should be included in the routine assessment of
advanced gastric cancer patients.
PMID- 25132774
TI - Risk factors associated with early and late HAT after adult liver
transplantation.
AB - AIM: To identify risk factors that might contribute to hepatic artery thrombosis
(HAT) after liver transplantation (LT). METHODS: The perioperative and follow-up
data of a total of 744 liver transplants, performed from February 1999 to July
2010, were retrospectively reviewed. HAT developed in 20 patients (2.7%). HAT was
classified as early (occurring in fewer than 30 d post LT) or late (occurring
more than 30 d post LT). Early HAT developed in 14 patients (1.9%). Late HAT
developed in 6 patients (0.8%). Risk factors associated with HAT were analysed
using the chi(2) test for univariate analysis and logistic regression for
multivariate analysis. RESULTS: Lack of ABO compatibility, recipient/donor weight
ratio >= 1.15, complex arterial reconstruction, duration time of hepatic artery
anastomosis > 80 min, duration time of operation > 10 h, dual grafts, number of
units of blood received intraoperatively >= 7, number of units of fresh frozen
plasma (FFP) received intraoperatively >= 6, postoperative blood transfusion and
postoperative FFP use were significantly associated with early HAT in the
univariate analysis (P < 0.1). After logistic regression, independent risk
factors associated with early HAT were recipient/donor weight ratio >= 1.15 (OR =
4.499), duration of hepatic artery anastomosis > 80 min (OR = 5.429), number of
units of blood received intraoperatively >= 7 (OR = 4.059) and postoperative
blood transfusion (OR = 6.898). Graft type (whole/living-donor/split), duration
of operation > 10 h, retransplantation, rejection reaction, recipients with
diabetes preoperatively and recipients with a high level of blood glucose or
diabetes postoperatively were significantly associated with late HAT in the
univariate analysis (P < 0.1). After logistic regression, the independent risk
factors associated with early HAT were duration of operation > 10 h (OR = 6.394),
retransplantation (OR = 21.793) and rejection reactions (OR = 16.936).
CONCLUSION: Early detection of these risk factors, strict surveillance protocols
by Doppler ultrasound and prophylactic anticoagulation for recipients at risk
might be determined prospectively.
PMID- 25132776
TI - Chronic permanent hypoxemia predisposes to mild elevation of liver stiffness.
AB - AIM: To evaluate the impact of long term permanent hypoxemia noticed in patients
with non operated congenital cyanogenic cyanotic cardiopathy on liver stiffness.
METHODS: We included ten adult patients with non operated inoperate cyanotic
cardiopathy and ten matched patients for age and gender admitted to the
gastroenterology department for proctologic diseases; Clinical and laboratory
data were collected [age, gender, body mass index, oxygen saturation, glutamate
oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), glycemia
and cholesterol]. Measurement of hepatic stiffness by transient elastography was
carried out in all patients using the Fibroscan device. All patients underwent an
echocardiography to eliminate congestive heart failure. RESULTS: Among the
patients with cyanotic cardiopathy, median liver stiffness 5.9 +/- 1.3 kPa was
greater than control group (4.7 +/- 0.4 kPa) (P = 0.008). Median levels of GOT,
GPT, gamma-glutamyltransferase, glycemia and cholesterol were comparable in
cardiopathy and control group. In regression analysis including age, gender, body
mass index, oxygen saturation, GOT, GPT, glycemia, cholesterol showed that only
oxygen saturation was related to liver stiffness (r = -0.63 P = 0.002).
CONCLUSION: Chronic permanent hypoxemia can induce mild increase of liver
stiffness, but further studies are needed to explore the histological aspects of
liver injury induced by chronic permanent hypoxemia.
PMID- 25132775
TI - Human liver stem/progenitor cells decrease serum bilirubin in hyperbilirubinemic
Gunn rat.
AB - AIM: To test the ability of adult-derived human liver stem/progenitor cells
(ADHLSC) from large scale cultures to conjugate bilirubin in vitro and in
bilirubin conjugation deficient rat. METHODS: ADHLSC from large scale cultures
were tested for their phenotype and for their capacity to conjugate bilirubin in
vitro after hepatogenic differentiation. In vivo, Gunn rats [uridine diphosphate
glucuronosyltransferase 1A1 (UGT1A1) deficient animal] were injected with ADHLSC
and cryopreserved hepatocytes (positive control). Two, 4, 13 and 27 wk post
transplantation, transplanted Gunn rat bilirubin serum levels were determined by
high performance liquid chromatography. Human transplanted cell engraftment was
assessed 27 wk post-transplantation using immunohistochemistry and RTqPCR.
RESULTS: Large scale culture conditions do not modify ADHLSC phenotype, ADHLSC
were able to specifically conjugate bilirubin. ADHLSC were intraportally injected
into Gunn rats and blood UCB was measured at different times post
transplantation, infused-Gunn rats exhibited a metabolic effect 3 mo post
transplantation and maintained over a 6 mo period. ADHLSC engraftment into Gunn
rat's liver was demonstrated by RTqPCR and immunohistochemistry against albumin
and UGT1A1. CONCLUSION: ADHLSC from large scale cultures are efficient in
conjugating bilirubin in vitro and in restoring a deficient metabolic function
(reducing bilirubin level) in hyperbilirubinemic rats.
PMID- 25132777
TI - Preoperative colonoscopy through the colonic stent in patients with colorectal
cancer obstruction.
AB - AIM: To evaluate the feasibility of a preoperative colonoscopy through a self
expendable metallic stent (SEMS) and to identify the factors that affect complete
colonoscopy. METHODS: A total of 48 patients who had SEMS placement because of
acute malignant colonic obstruction underwent preoperative colonoscopy. After
effective SEMS placement, patients who showed complete resolution of radiological
findings and clinical signs of acute colon obstruction underwent a standard bowel
preparation. Preoperative colonoscopy was then performed using a standard
colonoscope. If the passage of colonoscope was not feasible gastroscope was used.
After colonoscopy, cecal intubation time, grade of bowel preparation, tumor
location, stent location, presence of synchronous polyps or cancer, damage to
colonoscopy and bleeding, and stent migration after colonoscopy were recorded.
RESULTS: Complete evaluation with colonoscope was possible in 30 patients
(62.5%). In this group, adenoma was detected in 13 patients (43.3%). The factors
that affected complete colonoscopy were also analyzed: Tumor location at an
angle; stent placement at an angle; and stent expansion diameter, which affected
complete colonoscopy significantly. However in multivariate analysis, stent
expansion diameter was the only significant factor that affected complete
colonoscopy. Complete evaluation using additional gastroscope was feasible in 42
patients (87.5%). CONCLUSION: Preoperative colonoscopy through the colonic stent
using only conventional colonoscope was unfavorable. The narrow expansion
diameter of the stent may predict unfavorable outcome. In such a case, using
small caliber scope should be considered and may expect successful outcome.
PMID- 25132778
TI - Aerobic exercise improves gastrointestinal motility in psychiatric inpatients.
AB - AIM: To evaluate the benefit of aerobic exercise on colonic transit time (CTT)
for psychiatric inpatients in a closed ward. METHODS: Sixty consecutive adult
inpatients of the Somang Hospital Psychiatry Unit (Eumsung-gun, South Korea),
without CTT-related diseases or drug therapies, were recruited for study from
March to June of 2012. Upon enrollment, the patients were randomly assigned to
partake in a 12-wk instructor-led group aerobic exercise program (exercise group;
n = 30) or to maintain their ordinary daily activities (control group; n = 30).
The exercise program was structured as 10 min warm-up (stretching), 40 min
exercise, and 10 min cool-down (stretching) for three days each week. The
exercise sessions consisted of walking only in week one and aerobics from weeks
two to 12, with increasing intensity (50% heart rate reserve (HRR) for weeks one
to four, 60% HRR for weeks five to eight, and 70% HRR for weeks nine to 12). CTT
was measured before (baseline) and after (week 12) the exercise program, in
duplicate (on days four and seven), using abdominal radiography and the multiple
radio-opaque marker technique. Changes in the exercising patients' CTT and weight
, cardiovascular- and fitness-related parameters were statistically assessed.
RESULTS: The study dropout rate was 30.0%, with 23 patients in the exercise group
and 19 patients in the control group completing the study. At week 12, the
exercise group showed decreases in body weight (mean +/- SE) baseline: 69.4 +/-
2.8 vs study-end: 67.6 +/- 2.7; P < 0.635) and body mass index (BMI) (25.2 +/-
1.1 vs 24.9 +/- 0.8; P < 0.810), but the extent of change was not significantly
different from that experienced by the control group (body weight: 68.8 +/- 4.0
vs 68.8 +/- 3.9; BMI: 24.3 +/- 1.1 vs 24.4 +/- 1.2). However, the exercise group
showed significant improvements in leg muscle strength (baseline: 41.7 +/- 4.3 vs
study-end: 64.1 +/- 5.0; P < 0.001), cardio-respiratory endurance (120.5 +/- 4.5
vs 105.4 +/- 2.8; P < 0.004), and leg muscle elasticity and power output (21.5 +/
2.6 vs 30.6 +/- 2.8; P < 0.001). The exercise group showed an exercise-induced
reduction in total CTT (baseline: 54.2 +/- 8.0 vs 30.3 +/- 6.1), which was
significantly different from that experienced by the control group over the 12-wk
period (48.6 +/- 9.3 vs 48.3 +/- 12.3; P = 0.027); however, the exercise-induced
decreases in CTT involving the three colonic segments examined (right, left and
recto-sigmoid) showed no significant differences from the control group.
CONCLUSION: A 12-wk aerobic exercise program can benefit psychiatric inpatients
by increasing intestinal motility, possibly decreasing risk of metabolic- and
cardiovascular-related disease.
PMID- 25132779
TI - Diagnostic value of controlled attenuation parameter for liver steatosis in
patients with chronic hepatitis B.
AB - AIM: To study the diagnostic value of controlled attenuation parameter (CAP),
evaluated by transient elastography, for liver steatosis in patients with chronic
hepatitis B (CHB). METHODS: Eighty-eight patients with CHB were enrolled in this
study. All of the patients were subjected to transient elastography to determine
CAP. These patients also underwent liver biopsy in the same period. Using liver
biopsy as a reference, we determined receiver operating characteristic (ROC)
curves for different endpoints. Areas under the ROC curves (AUCs) were used to
evaluate the diagnostic importance of CAP for liver steatosis in patients with
CHB. RESULTS: A positive correlation was observed between the AUCs of CAP and
liver pathological stage (r = 0.582, P < 0.05). CAP was not correlated with
inflammation degree and fibrosis degree (r = -0.025, P > 0.05; r = 0. 068, P >
0.05). The mean CAP value at S0 was 209.59 +/- 41.25 dB/m, 223.84 +/- 35.28 dB/m
at S1, 274.17 +/- 43.69 dB/m at S2, and 312.50 +/- 25.44 dB/m at S3. CAP values
among S0, S1, S2, and S3 were significantly different (F = 17.79, P < 0.01). The
AUC values for CAP were 0.711 (0.592-0.870), 0.868 (0.748-0.989), and 0.974
(0.922-1.026) for S1, S2, and S3, respectively. The optimal cut-off values were
219.5, 230.0, and 283.5 dB/m. CONCLUSION: CAP is a novel tool that can be used to
assess the degree of steatosis.
PMID- 25132780
TI - Relationship between methylation and colonic inflammation in inflammatory bowel
disease.
AB - AIM: To investigate the relationship between the methylation status in the SLIT2
and TGFB2 promoters and colonic inflammation in inflammatory bowel disease
patients. METHODS: We evaluated the methylation status of 2 genes (SLIT2 and
TGFB2) in 226 biopsies taken from 62 colonoscopies of 38 patients (29 ulcerative
colitis and 9 Crohn's colitis) using methylation-specific melting curve analysis.
The relationships between methylation status and clinical, biological, endoscopic
and histological activities were evaluated. Twenty-three of the 38 patients had a
second colonoscopy and were included in a longitudinal analysis. Numerical
results were given as the means +/- SD of the sample and range, except when
specified. Student t analysis, U Mann Whitney and ANOVA factor were used to
compare the means. Qualitative results were based on the chi(2) test. RESULTS:
SLIT2 methylation was more frequent in samples with endoscopic activity than with
endoscopic remission (55% vs 18%, P < 0.001). SLIT2 methylation was also higher
in samples with acute inflammation (56.5%) than in samples with chronic (24%) or
absent inflammation (15%) (P < 0.001). For TGFB2 methylation, the correlation was
only significant with endoscopic activity. Methylation was higher in the distal
colon for both genes (P < 0.001 for SLIT2 and P = 0.022 for TGFB2). In the
multivariate analysis, only inflammation status (and not disease duration or
extension) was independently associated with SLIT2 methylation [OR = 6.6 (95%CI:
1.65-27.36), P = 0.009]. In the longitudinal analysis, the maintenance of
endoscopic remission was protective for methylation. CONCLUSION: Endoscopic and
histological inflammation are predictive for SLIT2 methylation.
PMID- 25132781
TI - Early viral kinetics during hepatitis C virus genotype 6 treatment according to
IL28B polymorphisms.
AB - AIM: To investigate the early viral kinetics and interleukin-28B (IL28B)
polymorphisms of hepatitis C genotype 6 during pegylated interferon and ribavirin
therapy. METHODS: Sixty-five patients with chronic hepatitis C virus (HCV)
infection treated with pegylated interferon and ribavirin (PEG-IFN/RBV) were
included, of whom 15 (23.1%), 16 (24.6%) and 34 (52.3%) patients were infected
with hepatitis C genotype 1 (HCV-1), genotype 3 (HCV-3) and genotype 6 (HCV-6),
respectively. Serum HCV-RNA levels were measured frequently during the first 4-wk
of therapy. DNA extracted from samples was analyzed for the IL28B single
nucleotide polymorphism (SNP) rs12979860 by polymerase chain reaction and direct
sequencing. RESULTS: During the first 4-wk of therapy, the mean viral decline for
patients with HCV-6 (5.55 +/- 1.82 log10IU/mL) was comparable to that of patients
with HCV-3 (5.55 +/- 1.82 log10IU/mL vs 5.86 +/- 1.02 log10IU/mL, P = 0.44) and
was significantly higher than patients with HCV-1 (5.55 +/- 1.82 log10IU/mL vs
4.23 +/- 1.99 log10IU/mL, P = 0.04). In the HCV-6 group, the first phase (days 0
2) viral decline was significantly higher in patients with the favorable
rs12979860 CC than non-CC genotypes (2.46 +/- 1.01 log10IU/mL/wk vs 1.70 +/- 0.67
log10IU/mL, respectively, P = 0.045). A statistically insignificant decrease in
the second-phase (days 7-28) decline was also found in patients with the CC
genotype than those with the non-CC genotype, though not significantly different
(1.24 +/- 0.64 log10IU/mL/wk vs 0.80 +/- 0.65 log10IU/mL/wk, respectively, P =
0.172). At baseline, the SNP genotype was an independent predictor of rapid
virological response but not of sustained virological response. CONCLUSION: The
IL28B genotype was linked to an impact on early viral kinetics in response to PEG
IFN/RBV therapy in HCV-6 infected patients.
PMID- 25132782
TI - Coagulopathy in a subtype of choledochal cyst and management strategy.
AB - AIM: To evaluated our management algorithm of the coagulopathy. We evaluated our
management algorithm of the coagulopathy. METHODS: Between October 2001 and
January 2013, 160 CDC children with coagulopathy (fibrinogen, FIB < 2 g/L) were
recruited. FIB >= 1 g/L is generally required for safe elective surgery. We used
FIB level as an indicator when: (1) patients with FIB levels between 1-2 g/L
underwent one-stage definitive operation; and (2) patients with FIB < 1 g/L
underwent 3 d of medical treatment. Thereafter, those with FIB >= 1 g/L underwent
one-stage definitive operation whereas those with FIB < 1 g/L underwent external
biliary drainage to allow liver function improvement. Those patients with liver
function improvements underwent definitive operation after 7 d of drainage.
RESULTS: After preoperative optimization, 92.5% of CDC children with coagulopathy
underwent successful one-stage definitive operation. The remaining 7.5% of CDC
children required initial external bile drainage, and underwent definitive
operation 11 d after the admission. The mean operative time and postoperative
recovery duration were comparable to those with normal coagulations. The median
follow-up period was 57 mo. No blood transfusion or other postoperative
complications were encountered. CONCLUSION: Following our management protocol,
the majority of CDC children with coagulopathy can be managed with one-stage
definitive operation.
PMID- 25132783
TI - Predictors for failure of stent treatment for benign esophageal perforations - a
single center 10-year experience.
AB - AIM: To investigate possible predictors for failed self-expandable metallic stent
(SEMS) therapy in consecutive patients with benign esophageal perforation-rupture
(EPR). METHODS: All patients between 2003-2013 treated for EPR at the Karolinska
University Hospital, a tertiary referral center, were studied with regard to
initial management with SEMS. Patients with malignancy as an underlying cause and
those with anastomotic leakages were excluded. Sealing of the perforation with a
covered SEMS was the primary strategy whenever feasible. Stent therapy failure
was defined as a radical change of treatment strategy due to uncontrolled
mediastinitis, which in this setting consisted of emergency esophagectomy with
end-esophagostomy or death as a consequence of the perforation and subsequent
uncontrolled sepsis. Patient and lesion characteristics were analyzed and are
presented as median and interquartile range. Possible predictors for failed stent
therapy were analyzed with uni-variate logistic regression, while variables with
P < 0.2 were further analyzed with multi-variate logistic regression. RESULTS: Of
the total number of 48 patients presenting with EPR, 40 patients (83.3%) were
treated with SEMS at the time of admission, with an intention to heal the
perforation. Twenty-three patients had Boerhaave's syndrome (58%), 16 had an
iatrogenic perforation (40%) and 1 had external trauma to the esophagus (3%). The
total in-hospital mortality, including the cases that had other initial
treatments (n = 8), was 10.4% and 7.5% among those who were subjected to the SEMS
based strategy. In 33 of the 40 patients (82.5%) who were treated with stent, the
EPR healed without further change in treatment strategy. Patients classified as
treatment success received a SEMS at a median time of 1 (1-1) d after the actual
EPR, compared to 3 (1-10) d among those where the initial treatment failed, P =
0.039 in uni-variate analysis and P = 0.052 in multi-variate analysis. No other
significant factors emerged, indicating an increased risk for failure. Six of 7
patients, where stent treatment of the defect failed, underwent an emergency
esophagectomy with end esophagostomy and one patient died. CONCLUSION: SEMS as an
upfront therapeutic strategy seems to be a successful concept, when applied to an
unselected group of patients with EPR.
PMID- 25132784
TI - Efficacy of morning-only 4 liter sulfa free polyethylene glycol vs 2 liter
polyethylene glycol with ascorbic acid for afternoon colonoscopy.
AB - AIM: To compare the bowel cleansing efficacy of same day ingestion of 4-L sulfa
free polyethylene glycol (4-L SF-PEG) vs 2-L polyethylene glycol solution with
ascorbic acid (2-L PEG + Asc) in patients undergoing afternoon colonoscopy.
METHODS: 206 patients (mean age 56.7 years, 61% male) undergoing outpatient
screening or surveillance colonoscopies were prospectively randomized to receive
either 4-L SF-PEG (n = 104) or 2-L PEG + Asc solution (n = 102). Colonoscopies
were performed by two blinded endoscopists. Bowel preparation was graded using
the Ottawa scale. Each participant completed a satisfaction and side effect
survey. RESULTS: There was no difference in patient demographics amongst groups.
4-L SF-PEG resulted in better Ottawa scores compared to 2-L PEG + Asc, 4.2 vs 4.9
(P = 0.0186); left colon: 1.33 vs 1.57 respectively (P = 0.0224), right colon:
1.38 vs 1.63 respectively (P = 0.0097). No difference in Ottawa scores was found
for the mid colon or amount of fluid. Patient satisfaction was similar for both
arms but those assigned to 4-L SF-PEG reported less bloating: 23.1% vs 11.5% (P =
0.0235). Overall polyp detection, adenomatous polyp and advanced adenoma
detection rates were similar between the two groups. CONCLUSION: Morning only 4-L
SF-PEG provided superior cleansing with less bloating as compared to 2-L PEG +
Asc bowel preparation for afternoon colonoscopy. Thus, future studies evaluating
efficacy of morning only preparation for afternoon colonoscopy should use 4-L SF
PEG as the standard comparator.
PMID- 25132785
TI - Selection of treatment modalities for Budd-Chiari Syndrome in China: a
preliminary survey of published literature.
AB - AIM: To evaluate the frequency of use of various treatment modalities for Budd
Chiari syndrome (BCS) in China by conducting a preliminary survey of relevant
literature. METHODS: All papers regarding the treatment of BCS in Chinese
patients were identified by searching PubMed, Chinese Scientific and
Technological Journal, and China National Knowledge Infrastructure databases.
Data regarding the number of BCS patients treated with different treatment
modalities over time were collected. The proportions of BCS patients undergoing
various treatment modalities were calculated. RESULTS: Overall, 300 of 3005
papers initially retrieved were included. These papers included 23352 BCS
patients treated with different treatment modalities. The treatment modalities
include surgery (n = 8625), interventional treatment (n = 13940), surgery
combined with interventional treatment (n = 363), medical therapy (n = 277),
other treatments (n = 91), and no treatment (n = 56). After 2005, the number of
BCS patients treated with surgery was drastically decreased, but the number of
BCS patients who underwent interventional treatment was almost maintained. Shunt
surgery was the most common type of surgery (n = 3610). Liver transplantation was
rarely employed (n = 2). Balloon angioplasty with or without stenting was the
most common type of interventional treatment (n = 13747). Transjugular
intrahepatic portosystemic shunt was rarely employed (n = 81). CONCLUSION:
Selection of treatment modalities for BCS might be different between China and
Western countries. Further work should be necessary to establish a unanimous
therapeutic strategy for BCS in China.
PMID- 25132786
TI - Symptomatic multinodular splenic hamartoma preoperatively suspected as metastatic
tumor: a case report.
AB - Splenic hamartoma (SH) is a rare benign tumor usually detected accidentally,
which is composed of an aberrant mixture of normal splenic elements. Here, we
report a case of 54-year-old man who presented with symptomatic multinodular SH
and was admitted initially for thrombocytopenia and anemia. Physical examination
revealed that the patients had an anemic appearance and palpable spleen,
extending 10 cm below the costal margin. Preoperative ultrasound and computed
tomography (CT) indicated splenomegaly with multinodular lesions. On enhanced CT
scanning, during the arterial phase, the lesions demonstrated inhomogeneous
enhancement, and in the portal phase the lesions were more hyperdense than the
splenic parenchyma. The images were highly suggestive of a metastatic tumor.
Splenectomy was performed 1 wk later. The tumor was eventually diagnosed as SH
according to the morphological features and immunohistochemical detection, by
which CD34 was positive in lining cells and some spindle cells, vimentin was
positive in the tumor, factor-VIII-related antigen was positive multifocally in
lining cells, and smooth muscle actin was positive in some spindle cells.
Thrombocytopenia and anemia were cured after splenectomy.
PMID- 25132788
TI - Collaborative work between the West and Asia.
AB - The "Collaborative Work between the West and Asia" session was chaired by Dr. Yih
Ing Hser and had three speakers. The speakers (and their topics) were: Dr. Gavin
Bart (Collaborative Addiction Research in Asian Populations Home and Abroad), Dr.
Li Li (Implementing Intervention Research Projects in Asia), and Dr. Le Minh
Giang (Building Research Infrastructure for International Collaborative Studies
on Substance Use Disorder and HIV: The Case of Hanoi Medical University/Vietnam).
PMID- 25132787
TI - Acute acalculous cholecystitis immediately after gastric operation: case report
and literatures review.
AB - Acute acalculous cholecystitis (AAC) is a rare complication of gastric surgery.
The most commonly accepted concepts regarding its pathogenesis are bile stasis,
sepsis and ischemia, but it has not been well described how to identify and
manage this disease in the early stage. We report three cases of AAC in elderly
patients immediately after gastric surgery, which were treated with three
different strategies. One patient died 42 d after emergency cholecystectomy, and
the other two finally recovered through timely cholecystostomy and percutaneous
transhepatic gallbladder drainage, respectively. These cases informed us of the
value of early diagnosis and proper treatment for perioperative AAC after gastric
surgery. We further reviewed reported cases of AAC immediately after gastric
operation, which may expand our knowledge of this disease.
PMID- 25132789
TI - Synthesis, central nervous system activity, and structure-activity relationship
of 1-aryl-6-benzyl-7-hydroxy-2,3-dihydroimidazo[1,2-a]pyrimidine-5(1H)-ones.
AB - A series of 24 1-aryl-6-benzyl-7-hydroxy-2,3-dihydroimidazo[1,2-a]pyrimidine
5(1H)-ones was designed as antinociceptive compounds acting through opioid
receptors with additional serotoninergic activity. The compounds, similarly as
previously published series, lack the protonable nitrogen atom which is a part of
classical opioid receptor pharmacophore and is necessary to interact with the
conserved Asp(3.32) in the opioid receptor binding pocket. The compounds were
obtained in one-step cyclocondensation of 1-aryl-4,5-dihydro-1H-imidazol-2-amines
diethyl 2-benzylmalonate or diethyl 2-(2-chlorobenzyl)malonate under basic
conditions. Almost all the tested compounds exerted strong antinociceptive
activity, but surprisingly, it was not reversed by naloxone; thus, it is not
mediated through opioid receptors. It makes it possible to conclude that addition
of one more aromatic moiety to the non-classical opioid receptor pharmacophore
results in the compounds which are not opioid receptor ligands. The lack of
activity of one of the tested compounds may be attributed to low blood-brain
barrier permeation or unfavorable distribution of electrostatic potential and
HOMO and LUMO orbitals.
PMID- 25132790
TI - THE RELATIONSHIP BETWEEN MALE-PERPETRATED INTERPARENTAL AGGRESSION, PATERNAL
CHARACTERISTICS, AND CHILD PSYCHOSOCIAL FUNCTIONING.
AB - It is well established that children in homes where interparental violence is
present are at increased risk for psychosocial (i.e., internalizing,
externalizing, and attention) difficulties. However, previous studies have
provided a limited view on the variety of factors that commonly co-occur in these
environments (e.g., other characteristics of the parents and family) and how they
may collectively impact children. Knowing this information could have
implications for parental interventions aimed at preventing the continuation or
initiation of psychosocial problems in children. Thus, the present study
simultaneously examined the association between father-perpetrated interparental
aggression, father characteristics, and child psychosocial functioning in a
sample of 145 men arrested for domestic violence. Results showed that of all the
variables examined, paternal antisocial personality traits and interpersonal
hostility were uniquely associated with overall child psychosocial impairment,
externalizing problems, and attention problems. Implications for intervention
programs are discussed.
PMID- 25132791
TI - Robust measurement of individual localized changes to the aging hippocampus.
AB - Alzheimer's Disease (AD) is characterized by a stereotypical spatial pattern of
hippocampus (HP) atrophy over time, but reliable and precise measurement of
localized longitudinal change to individual HP in AD have been elusive. We
present a method for quantifying subject-specific spatial patterns of
longitudinal HP change that aligns serial HP surface pairs together, cuts slices
off the ends of the HP that were not shared in the two delineations being
aligned, estimates weighted correspondences between baseline and follow-up HP,
and finds a concise set of localized spatial change patterns that explains HP
changes while down-weighting HP surface points whose estimated changes are
biologically implausible. We tested our method on a synthetic HP change dataset
as well as a set of 320 real elderly HP measured at 1-year intervals. Our results
suggests that the proposed steps reduce the amount of implausible HP changes
indicated among individual HP, increase the strength of association between HP
change and cognitive function related to AD, and enhance the estimation of
reliable spatially-localized HP change patterns.
PMID- 25132792
TI - ISOLATION OF GLYCOSIDES FROM THE BARKS OF ILEX ROTUNDA BY HIGH-SPEED COUNTER
CURRENT CHROMATOGRAPHY.
AB - Semi-preparative and preparative high-speed counter-current chromatography
(HSCCC) were successfully used for isolation of glycosides from 50% ethanol
extract of the dried barks of Ilex rotunda Thunb. (Aquifoliaceae) by using a two
phase solvent system composed of ethyl acetate-n-butanol-water (1:6:7, v/v/v).
From 1.0 g of the extract, syringaresinol 4',4"-di-o-beta-d-glucopyranoside (I,
20.2 mg),, syringin (II, 56.8 mg), sinapaldehyde glucoside (III, 26.2 mg),,
syringaresinol 4'-o-beta-d-glucopyranoside (IV, 20.4 mg), and pedunculoside (V,
45.1 mg) were obtained by one run of TBE-1000A HSCCC instrument with 1000 mL of
column volume. Their structures were identified by IR, MS, and 1H and 13C NMR
studies. Glycoside I was isolated from this plant for the first time.
PMID- 25132793
TI - Disclosure of Positive BRCA1/2-Mutation Status in Young Couples: The Journey From
Uncertainty to Bonding Through Partner Support.
AB - BRCA1/2-positive women who learn their mutation status early in the life-course
face unique challenges related to navigating the tasks of young adulthood. Using
qualitative methods and grounded theory, the authors analyzed in-depth interviews
with 11 women aged 26 to 35 who learned their mutation status before marriage.
Their narratives illustrate the complexity of relationship formation, and
highlight the potential for relationship-bonding and intimacy-building in the
course of sharing mutation information. Disclosing BRCA mutation status to dating
partners is often preceded by feelings of fear and anxiety, yet many participants
reported that doing so has positive effects on relationships. Partners' abilities
to respond with interest, empathy, and affection are associated with in creased
future intimacy, consistent with generally accepted principles within the
family/couple systems field. Individual cancer risk perception and familial
cancer experiences may affect the disclosure experience, which can be understood
via Attachment Theory. Our findings provide clinical insight, identify new areas
for research, and suggest ways to assist this unique population in their
adjustment to being BRCA mutation-positive.
PMID- 25132794
TI - Spatial Resolution Requirements for Traffic-Related Air Pollutant Exposure
Evaluations.
AB - Vehicle emissions represent one of the most important air pollution sources in
most urban areas, and elevated concentrations of pollutants found near major
roads have been associated with many adverse health impacts. To understand these
impacts, exposure estimates should reflect the spatial and temporal patterns
observed for traffic-related air pollutants. This paper evaluates the spatial
resolution and zonal systems required to estimate accurately intraurban and near
road exposures of traffic-related air pollutants. The analyses use the detailed
information assembled for a large (800 km2) area centered on Detroit, Michigan,
USA. Concentrations of nitrogen oxides (NOx) due to vehicle emissions were
estimated using hourly traffic volumes and speeds on 9,700 links representing all
but minor roads in the city, the MOVES2010 emission model, the RLINE dispersion
model, local meteorological data, a temporal resolution of 1 hr, and spatial
resolution as low as 10 m. Model estimates were joined with the corresponding
shape files to estimate residential exposures for 700,000 individuals at property
parcel, census block, census tract, and ZIP code levels. We evaluate joining
methods, the spatial resolution needed to meet specific error criteria, and the
extent of exposure misclassification. To portray traffic-related air pollutant
exposure, raster or inverse distance-weighted interpolations are superior to
nearest neighbor approaches, and interpolations between receptors and points of
interest should not exceed about 40 m near major roads, and 100 m at larger
distances. For census tracts and ZIP codes, average exposures are overestimated
since few individuals live very near major roads, the range of concentrations is
compressed, most exposures are misclassified, and high concentrations near roads
are entirely omitted. While smaller zones improve performance considerably, even
block-level data can misclassify many individuals. To estimate exposures and
impacts of traffic-related pollutants accurately, data should be geocoded or
estimated at the most-resolved spatial level; census tract and larger zones have
little if any ability to represent intraurban variation in traffic-related air
pollutant concentrations. These results are based on one of the most
comprehensive intraurban modeling studies in the literature and results are
robust. Recommendations address the value of dispersion models to portray spatial
and temporal variation of air pollutants in epidemiology and other studies;
techniques to improve accuracy and reduce the computational burden in urban scale
modeling; the necessary spatial resolution for health surveillance, demographic,
and pollution data; and the consequences of low resolution data in terms of
exposure misclassification.
PMID- 25132796
TI - Endogenous retroviruses in domestic animals.
AB - Endogenous retroviruses (ERVs) are genomic elements that are present in a wide
range of vertebrates. Although the study of ERVs has been carried out mainly in
humans and model organisms, recently, domestic animals have become important, and
some species have begun to be analyzed to gain further insight into ERVs. Due to
the availability of complete genomes and the development of new computer tools,
ERVs can now be analyzed from a genome-wide viewpoint. In addition, more
experimental work is being carried out to analyze the distribution, expression
and interplay of ERVs within a host genome. Cats, cattle, chicken, dogs, horses,
pigs and sheep have been scrutinized in this manner, all of which are interesting
species in health and economic terms. Furthermore, several studies have noted
differences in the number of endogenous retroviruses and in the variability of
these elements among different breeds, as well as their expression in different
tissues and the effects of their locations, which, in some cases, are near genes.
These findings suggest a complex, intriguing relationship between ERVs and host
genomes. In this review, we summarize the most important in silico and
experimental findings, discuss their implications and attempt to predict future
directions for the study of these genomic elements.
PMID- 25132797
TI - Using current data to define new approach in age related macular degeneration:
need to accelerate translational research.
AB - Age related macular degeneration (AMD) is one of the major retinal degenerative
disease of ageing whose complex genetic basis remains undeciphered. The
involvement of various other factors like mitochondrial genes, cytoskeletal
proteins and the role of epigenetics has been described in this review. Several
population based AMD genetic studies have been carried out worldwide. Despite the
increased publication of reports, clinical translation still eludes this
davastating disease. We suggest models to address roadblocks in clinical
translation hoping that these would be beneficial to drive AMD research towards
innovative biomarkers and therapeutics Therefore, addressing the need large
autopsy studies and combining it with efficient use of bioinformatic tools,
statistical modeling and probing SNP-biomarker association are key to time bound
resolution of this disease.
PMID- 25132795
TI - Spatial and temporal simulation of human evolution. Methods, frameworks and
applications.
AB - Analyses of human evolution are fundamental to understand the current gradients
of human diversity. In this concern, genetic samples collected from current
populations together with archaeological data are the most important resources to
study human evolution. However, they are often insufficient to properly evaluate
a variety of evolutionary scenarios, leading to continuous debates and
discussions. A commonly applied strategy consists of the use of computer
simulations based on, as realistic as possible, evolutionary models, to evaluate
alternative evolutionary scenarios through statistical correlations with the real
data. Computer simulations can also be applied to estimate evolutionary
parameters or to study the role of each parameter on the evolutionary process.
Here we review the mainly used methods and evolutionary frameworks to perform
realistic spatially explicit computer simulations of human evolution. Although we
focus on human evolution, most of the methods and software we describe can also
be used to study other species. We also describe the importance of considering
spatially explicit models to better mimic human evolutionary scenarios based on a
variety of phenomena such as range expansions, range shifts, range contractions,
sex-biased dispersal, long-distance dispersal or admixtures of populations. We
finally discuss future implementations to improve current spatially explicit
simulations and their derived applications in human evolution.
PMID- 25132798
TI - Temporally and spatially restricted gene expression profiling.
AB - Identifying gene function in specific cells is critical for understanding the
processes that make cells unique. Several different methods are available to
isolate actively transcribed RNA or actively translated RNA in specific cells at
a chosen time point. Cell-specific mRNA isolation can be accomplished by the
expression of transgenes in cells of interest, either directly from a specific
promoter or using a modular system such as Gal4/UAS or Cre/lox. All of the
methods described in this review, namely thiol-labeling of RNA (TU-tagging or
RABT), TRAP (translating ribosome affinity purification) and INTACT (isolation of
nuclei tagged in specific cell types), allow next generation sequencing,
permitting the identification of enriched gene transcripts within the specific
cell-type. We describe here the general concept of each method, include examples,
evaluate possible problems related to each technique, and suggest the types of
questions for which each method is best suited.
PMID- 25132801
TI - Electron Cryo-Microscopy Studies of Helminthosporium victoriae Virus 190S.
PMID- 25132799
TI - Impact of next generation sequencing techniques in food microbiology.
AB - Understanding the Maxam-Gilbert and Sanger sequencing as the first generation, in
recent years there has been an explosion of newly-developed sequencing
strategies, which are usually referred to as next generation sequencing (NGS)
techniques. NGS techniques have high-throughputs and produce thousands or even
millions of sequences at the same time. These sequences allow for the accurate
identification of microbial taxa, including uncultivable organisms and those
present in small numbers. In specific applications, NGS provides a complete
inventory of all microbial operons and genes present or being expressed under
different study conditions. NGS techniques are revolutionizing the field of
microbial ecology and have recently been used to examine several food ecosystems.
After a short introduction to the most common NGS systems and platforms, this
review addresses how NGS techniques have been employed in the study of food
microbiota and food fermentations, and discusses their limits and perspectives.
The most important findings are reviewed, including those made in the study of
the microbiota of milk, fermented dairy products, and plant-, meat- and fish
derived fermented foods. The knowledge that can be gained on microbial diversity,
population structure and population dynamics via the use of these technologies
could be vital in improving the monitoring and manipulation of foods and
fermented food products. They should also improve their safety.
PMID- 25132802
TI - Public discourse on HIV/AIDS: an archival analysis of national newspaper
reporting in Uganda, 1996-2011.
AB - Uganda is recognised as an early success story in the HIV epidemic at least in
part due to an open and vigorous national dialogue about HIV prevention. This
study examined the national discourse about HIV, AIDS, and young people in New
Vision, Uganda's leading national newspaper between 1996 and 2011, building from
a previous archival analysis of New Vision reporting by Kirby (1986-1995). We
examined the continuing evolution in the public discourse in Uganda, focusing on
reporting about young people. An increase in reporting on HIV and AIDS occurred
after 2003, as antiretroviral treatment was becoming available. While the
emphasis in newspaper reporting about adults and the population at large evolved
to reflect the development of new HIV treatment and prevention methods, the
majority of the articles focused on young people did not change. Articles about
young people continued to emphasise HIV acquisition due to early and premarital
sexual activity and the need for social support services for children affected by
HIV and AIDS. Articles often did not report on the complex social conditions that
shape HIV-related risk among young people, or address young people who are
sexually active, married, and/or HIV infected. With HIV prevalence now increasing
among young people and adults in Uganda, greater attention to HIV prevention is
needed.
PMID- 25132800
TI - A Comprehensive Review of Dysregulated miRNAs Involved in Cervical Cancer.
AB - MicroRNAs(miRNAs) have become the center of interest in oncology. In recent
years, various studies have demonstrated that miRNAs regulate gene expression by
influencing important regulatory genes and thus are responsible for causing
cervical cancer. Cervical cancer being the third most diagnosed cancer among the
females worldwide, is the fourth leading cause of cancer related mortality.
Prophylactic human papillomavirus (HPV) vaccines and new HPV screening tests,
combined with traditional Pap test screening have greatly reduced cervical
cancer. Yet, thousands of women continue to be diagnosed with and die of this
preventable disease annually. This has necessitated the scientists to ponder over
ways of evolving new methods and chalk out novel treatment protocols/strategies.
As miRNA deregulation plays a key role in malignant transformation of cervical
cancer along with its targets that can be exploited for both prognostic and
therapeutic strategies, we have collected and reviewed the role of miRNA in
cervical cancer. A systematic search was performed using PubMed for articles that
report aberrant expression of miRNA in cervical cancer. The present review
provides comprehensive information for 246 differentially expressed miRNAs
gathered from 51 published articles that have been implicated in cervical cancer
progression. Of these, more than 40 miRNAs have been reported in the literature
in several instances signifying their role in the regulation of cancer. We also
identified 40 experimentally validated targets, studied the cause of miRNAs
dysregulation along with its mechanism and role in different stages of cervical
cancer. We also identified and analysed miRNA clusters and their expression
pattern in cervical cancer. This review is expected to further enhance our
understanding in this field and serve as a valuable reference resource.
PMID- 25132804
TI - Eating fish for two.
AB - This article is based on the British Nutrition Foundation's Annual Lecture, which
focused on maternal fish consumption and the effects of methylmercury (MeHg) on
fetal development, with respect to current guidance and policy on fish
consumption during pregnancy. Fish makes a valuable contribution to nutrient
intakes across the globe and is the primary protein source for many individuals,
particularly those in the developing world. Populations with a high fish
consumption, such as in the Republic of the Seychelles, have a greater exposure
to MeHg, which is present in varying amounts in all fish. Methylmercury is a
toxic pollutant, which is known to impair neurodevelopment. The dose of MeHg from
fish consumption, however, needed to impair neurodevelopment is unknown. Current
UK and US guidance on fish consumption during pregnancy tend to focus more on
avoiding risks rather than highlighting the benefits which can be obtained from
eating fish. Such recommendations have been mainly based on data arising from
epidemiological studies in the Faroe Islands, where methylmercury exposure was
largely from pilot whale consumption. Although small adverse effects on child
development have been reported in data from the Faroe Islands, data from the on
going Seychelles Child Development Studies have shown no adverse effects of
prenatal methlymercury exposure from high maternal fish consumption (9-12 meals
containing fish per week) on developmental outcomes. Instead these data suggest
that nutrients, including long chain polyunsaturated fatty acids (LC-PUFAs),
provided by fish may offer a beneficial effect and attenuate or modify any
effects of MeHg on developmental outcomes. Recent expert consultations have
concluded that the health benefits of fish consumption outweigh the risks posed
by MeHg exposure and have argued the need for improved education and guidance to
highlight the importance of consuming nutrients, including LC-PUFAs, from fish
for optimal child development and to encourage fish consumption during pregnancy.
PMID- 25132803
TI - Effect of ischemic and pharmacological preconditioning of lower limb muscle
tissue on tissue oxygenation measured by near-infrared spectroscopy--a pilot
study.
AB - BACKGROUND: Ischemic or volatile anesthetic preconditioning is defined as tissue
protection from impending ischemic cell damage by repetitive short periods of
tissue exposure to ischemia or volatile anesthetics. Objective of this study was
to elucidate, if ischemic preconditioning and pharmacological preconditioning
with sevoflurane have effects on muscle tissue oxygen saturation in patients
undergoing surgical revascularization of the lower limb. METHODS: In this
prospective randomized pilot study ischemic and pharmacological (sevoflurane)
preconditioning was performed in 40 patients with lower limb arterial occlusive
disease undergoing surgical revascularization. Sevoflurane preconditioning was
performed in one group (N = 20) by repetitive application of sevoflurane for six
minutes interspersed by six minutes of washout. Thereafter, ischemic
preconditioning was performed in all patients (N = 40) by repetitive clamping of
the femoral artery for six minutes interspersed by six minutes of reperfusion.
The effect of both procedures on leg muscle tissue oxygen saturation (rSO2) was
measured by near-infrared spectroscopy during both procedures and during surgery
and reperfusion (INVOS(r) 5100C Oxymeter with Small Adult SomaSensor(r) SAFB-SM,
Somanetics, Troy, Michigan, USA). RESULTS: Repetitive clamping and reperfusion of
the femoral artery resulted in significant cyclic decrease and increase of muscle
rSO2 (p < 0.0001). Pharmacological preconditioning with sevoflurane resulted in a
faster and higher increase of rSO2 during postoperative reperfusion (Maximal 111%
baseline +/- 20 versus 103% baseline +/- 14, p = 0.008) consistent with an
additional effect of pharmacological preconditioning on leg perfusion.
CONCLUSIONS: Ischemic preconditioning of lower limb muscle tissue and
pharmacological preconditioning with sevoflurane have an effect on tissue
oxygenation in patients with lower limb occlusive arterial disease. TRIAL
REGISTRATION: The trial has been registrated at http://www.ClinicalTrial.gov,
TRIAL NUMBER: NCT02038062 at 14 January 2014.
PMID- 25132805
TI - Facilitators and barriers influencing patient safety in Swedish hospitals: a
qualitative study of nurses' perceptions.
AB - BACKGROUND: Sweden has undertaken many national, regional, and local initiatives
to improve patient safety since the mid-2000s, but solid evidence of
effectiveness for many solutions is often lacking. Nurses play a vital role in
patient safety, constituting 71% of the workforce in Swedish health care. This
interview study aimed to explore perceived facilitators and barriers influencing
patient safety among nurses involved in the direct provision of care. Considering
the importance of nurses with regard to patient safety, this knowledge could
facilitate the development and implementation of better solutions. METHODS: A
qualitative study with semi-structured individual interviews was carried out. The
study population consisted of 12 registered nurses at general hospitals in
Sweden. Data were analyzed using qualitative content analysis. RESULTS: The
nurses identified 22 factors that influenced patient safety within seven
categories: 'patient factors', 'individual staff factors', 'team factors', 'task
and technology factors', 'work environment factors', 'organizational and
management factors', and 'institutional context factors'. Twelve of the 22
factors functioned as both facilitators and barriers, six factors were perceived
only as barriers, and four only as facilitators. There were no specific patterns
showing that barriers or facilitators were more common in any category.
CONCLUSION: A broad range of factors are important for patient safety according
to registered nurses working in general hospitals in Sweden. The nurses
identified facilitators and barriers to improved patient safety at multiple
system levels, indicating that complex multifaceted initiatives are required to
address patient safety issues. This study encourages further research to achieve
a more explicit understanding of the problems and solutions to patient safety.
PMID- 25132807
TI - Separating Octadecyltrimethoxysilane Hydrolysis and Condensation at the Air/Water
Interface through Addition of Methyl Stearate.
AB - The hydrolysis and condensation of octadecyltrimethoxysilane (OTMS) at the
air/water interface were monitored through molecular area changes at a constant
surface pressure of 10 mN/m. The onset of condensation was delayed through the
addition of methyl stearate (SME) acting as an inert filler molecule. In the
absence of SME, complete gelation of OTMS required 30 h, during which time OTMS
condensation occurred concomitantly with hydrolysis. In the presence of SME, the
OTMS monolayer gelation rate increased in proportion to the amount of SME
present. A 1:6 OTMS:SME molar ratio resulted in monolayer gelation within 30 min,
suggesting completion of monomer hydrolysis prior to condensation. These findings
indicate that lability of OTMS to hydrolysis at the air/water interface is
governed by steric and conformational constraints at the silicon atom site, with
monomeric OTMS being much more reactive than oligomeric OTMS. Fluorescence
microscope images demonstrated that the OTMS condensed domain size also decreased
with increasing SME concentrations, further implicating SME's role as an inert
filler.
PMID- 25132806
TI - Decreased percentage of CD4(+)Foxp3(+)TGF-beta(+) and increased percentage of
CD4(+)IL-17(+) cells in bronchoalveolar lavage of asthmatics.
AB - BACKGROUND: Asthma is a chronic inflammatory disorder of the airways with the
proven role of Th2 cells in its pathogenesis. The role and characteristic of
different subsets of CD4(+) cells is much less known. AIM: The aim of the study
was to analyze the incidence of different subsets of CD4(+) T cells, in
particular different subsets of CD4(+) cells with the co-expression of different
cytokines. METHODS: Twenty five stable asthmatic and twelve age-matched control
subjects were recruited to the study. Bronchoscopy and bronchoalveolar lavage
(BAL) were performed in all study subjects. CD4(+) T cells were isolated from BAL
fluid by positive magnetic selection. After stimulation simultaneous expression
of TGF-beta, FoxP3, CD25, IFN-gamma, IL-4, TNF-alpha (set 1); IL-10, FoxP3, CD25,
IFN-gamma, IL-4, MIP-1beta (set 2); IL-17A, IL-8, IFN-gamma, IL-4, MIP-1beta (set
3) were measured by flow cytometry. RESULTS: The percentage of CD4(+) cells co
expressing Foxp3 and TGF-beta (CD4(+)Foxp3(+)TGF-beta(+) cells) was significantly
lower (P = 0.03), whereas the percentage of CD4(+)IL-17(+) cells (P = 0.008),
CD4(+)IL-17(+) IFN-gamma(+) cells (P = 0.047) and CD4(+)IL-4(+) cells (P = 0.01)
were significantly increased in asthmatics compared with that seen in healthy
subjects. A significantly higher percentage of CD4(+)Foxp3(+) cells from asthma
patients expressed IFN-gamma (P = 0.01), IL-4 (P = 0.004) and CD25 (P = 0.04),
whereas the percentage of CD4(+)IL-10(+) cells expressing Foxp3 was significantly
decreased in asthmatics (P = 0.03). FEV1% predicted correlated negatively with
the percentage of CD4(+)IL-17(+) cells (r = -0.33; P = 0.046) and positively with
CD4(+)Foxp3(+)TGF-beta(+) cells (r = 0.43; P = 0.01). CONCLUSIONS: Our results
suggest that in the airways of chronic asthma patients there is an imbalance
between increased numbers of CD4(+)IL-17(+) cells and Th2 cells and decreased
number of CD4(+)Foxp3(+)TGF-beta(+).
PMID- 25132808
TI - MRI-Derived 3-D-Printed Breast Phantom for Microwave Breast Imaging Validation.
AB - We propose a 3-D-printed breast phantom for use in preclinical experimental
microwave imaging studies. The phantom is derived from an MRI of a human subject;
thus, it is anthropomorphic, and its interior is very similar to an actual
distribution of fibroglandular tissues. Adipose tissue in the breast is
represented by the solid plastic (printed) regions of the phantom, while
fibroglandular tissue is represented by liquid-filled voids in the plastic. The
liquid is chosen to provide a biologically relevant dielectric contrast with the
printed plastic. Such a phantom enables validation of microwave imaging
techniques. We describe the procedure for generating the 3-D-printed breast
phantom and present the measured dielectric properties of the 3-D-printed plastic
over the frequency range 0.5-3.5 GHz. We also provide an example of a suitable
liquid for filling the fibroglandular voids in the plastic.
PMID- 25132810
TI - On the Existence and Uniqueness of the Scientific Method.
AB - The ultimate utility of science is widely agreed upon: the comprehension of
reality. But there is much controversy about what scientific understanding
actually means, and how we should proceed in order to gain new scientific
understanding. Is there a method for acquiring new scientific knowledge? Is this
method unique and universal? There has been no shortage of proposals, but neither
has there been a shortage of skeptics about these proposals. This article
proffers for discussion a potential scientific method that aspires to be unique
and universal and is rooted in the recent and ancient history of scientific
thinking. Curiously, conclusions can be inferred from this scientific method that
also concern education and the transmission of science to others.
PMID- 25132809
TI - L-leucine, beta-hydroxy-beta-methylbutyric acid (HMB) and creatine monohydrate
prevent myostatin-induced Akirin-1/Mighty mRNA down-regulation and myotube
atrophy.
AB - BACKGROUND: The purpose of this study was to examine if L-leucine (Leu), beta
hydroxy-beta-methylbutyrate (HMB), or creatine monohydrate (Crea) prevented
potential atrophic effects of myostatin (MSTN) on differentiated C2C12 myotubes.
METHODS: After four days of differentiation, myotubes were treated with MSTN (10
ng/ml) for two additional days and four treatment groups were studied: 1) 3x per
day 10 mM Leu, 2) 3x per day 10 mM HMB, 3) 3x per day 10 mM Crea, 4) DM only.
Myotubes treated with DM without MSTN were analyzed as the control condition
(DM/CTL). Following treatment, cells were analyzed for total protein, DNA
content, RNA content, muscle protein synthesis (MPS, SUnSET method), and fiber
diameter. Separate batch treatments were analyzed for mRNA expression patterns of
myostatin-related genes (Akirin-1/Mighty, Notch-1, Ski, MyoD) as well as
atrogenes (MuRF-1, and MAFbx/Atrogin-1). RESULTS: MSTN decreased fiber diameter
approximately 30% compared to DM/CTL myotubes (p < 0.001). Leu, HMB and Crea
prevented MSTN-induced atrophy. MSTN did not decrease MPS levels compared to
DM/CTL myotubes, but MSTN treatment decreased the mRNA expression of Akirin
1/Mighty by 27% (p < 0.001) and MyoD by 26% (p < 0.01) compared to DM/CTL
myotubes. shRNA experiments confirmed that Mighty mRNA knockdown reduced myotube
size, linking MSTN treatment to atrophy independent of MPS. Remarkably, MSTN +
Leu and MSTN + HMB myotubes had similar Akirin-1/Mighty and MyoD mRNA levels
compared to DM/CTL myotubes. Furthermore, MSTN + Crea myotubes exhibited a 36% (p
< 0.05) and 86% (p < 0.001) increase in Akirin-1/Mighty mRNA compared to DM/CTL
and MSTN-only treated myotubes, respectively. CONCLUSIONS: Leu, HMB and Crea may
reduce MSTN-induced muscle fiber atrophy by influencing Akirin-1/Mighty mRNA
expression patterns. Future studies are needed to examine if Leu, HMB and Crea
independently or synergistically affect Akirin-1/Mighty expression, and how
Akirin-1/Mighty expression mechanistically relates to skeletal muscle hypertrophy
in vivo.
PMID- 25132811
TI - Silicon/organic hybrid heterojunction infrared photodetector operating in the
telecom regime.
AB - The authors report on the fabrication of a silicon/organic heterojunction based
IR photodetector. It is demonstrated that an Al/p-Si/perylene-derivative/Al
heterostructure exhibits a photovoltaic effect up to 2.7 MUm (0.46 eV), a value
significantly lower than the bandgap of either material. Although the devices are
not optimized, at room temperature a rise time of 300 ns, a responsivity of ~0.2
mA/W with a specific detectivity of D* ~ 7 * 107 Jones at 1.55 MUm is found. The
achieved responsivity is two orders of magnitude higher compared to our previous
efforts [1,2]. It will be outlined that the photocurrent originates from an
absorption mechanism involving excitation of an electron from the Si valence band
into the extended LUMO state in the perylene-derivative, with possible
participation of intermediate localized surface state in the organic material.
The non-invasive deposition of the organic interlayer onto the Si results in
compatibility with the CMOS process, making the presented approach a potential
alternative to all inorganic device concepts.
PMID- 25132812
TI - Jumping on the Train of Personalized Medicine: A Primer for Non-Geneticist
Clinicians: Part 1. Fundamental Concepts in Molecular Genetics.
AB - With the decrease in sequencing cost and the rise of companies providing
sequencing services, it is likely that personalized whole-genome sequencing will
eventually become an instrument of common medical practice. We write this series
of three reviews to help non-geneticist clinicians get ready for the major
breakthroughs that are likely to occur in the coming years in the fast-moving
field of personalized medicine. This first paper focuses on the fundamental
concepts of molecular genetics. We review how recombination occurs during
meiosis, how de novo genetic variations including single nucleotide polymorphisms
(SNPs), insertions and deletions are generated and how they are inherited from
one generation to the next. We detail how genetic variants can impact protein
expression and function, and summarize the main characteristics of the human
genome. We also explain how the achievements of the Human Genome Project, the
HapMap Project, and more recently, the 1000 Genomes Project, have boosted the
identification of genetic variants contributing to common diseases in human
populations. The second and third papers will focus on genetic epidemiology and
clinical applications in personalized medicine.
PMID- 25132813
TI - Gender effects and sexual-orientation impact on androstadienone-evoked behavior
and neural processing.
AB - In humans, the most established and investigated substance acting as a
chemosignal, i.e., a substance that is excreted from the body, is 4,16
androstadien-3-one (AND). AND, which is found in sweat and saliva, is known to be
responsible for influencing several variables, such as psychophysiological
status, behavior, as well as cortical processing. The aim of the present review
is to give insight into the variety of AND effects, with special regard to
specific cross-sexual characteristics of this putative human chemosignal,
emphasizing the neural activation patterns and factors such as contextual
conditions. This review highlights the importance of including those contributing
factors into the analysis of behavioral as well as brain-related studies.
PMID- 25132815
TI - Quantification of a secondary task-specific tremor in a violinist after a
temporal lobectomy.
AB - Task-specific tremors (TSTs) occur mainly during certain tasks and may be highly
disabling. In this case study, we report on a 66-year-old violinist who developed
a TST of the right arm only while playing the violin 4 weeks after a temporal
lobectomy, which had been performed as a result of his temporal lobe epilepsy.
Since a similar case, to our knowledge, has not been reported so far, our aim was
to quantitatively assess and describe the tremor by measuring (a) the
electromyography (EMG) activity of the wrist flexor and extensor as well as (b)
an accelerometer signal of the hand. We found a tremor-related frequency of about
7 Hz. Furthermore, at a similar frequency of about 7 Hz, there was coherence
between the tremor acceleration and EMG-activity of the wrist flexor and extensor
as well as between the tremor acceleration and coactivation. The tremorgenesis
remains unclear, and possible explanations can only be speculative.
PMID- 25132816
TI - Understanding human perception by human-made illusions.
AB - IT MAY BE FUN TO PERCEIVE ILLUSIONS, BUT THE UNDERSTANDING OF HOW THEY WORK IS
EVEN MORE STIMULATING AND SUSTAINABLE: They can tell us where the limits and
capacity of our perceptual apparatus are found-they can specify how the
constraints of perception are set. Furthermore, they let us analyze the cognitive
sub-processes underlying our perception. Illusions in a scientific context are
not mainly created to reveal the failures of our perception or the dysfunctions
of our apparatus, but instead point to the specific power of human perception.
The main task of human perception is to amplify and strengthen sensory inputs to
be able to perceive, orientate and act very quickly, specifically and
efficiently. The present paper strengthens this line of argument, strongly put
forth by perceptual pioneer Richard L. Gregory (e.g., Gregory, 2009), by
discussing specific visual illusions and how they can help us to understand the
magic of perception.
PMID- 25132817
TI - Inter-individual cognitive variability in children with Asperger's syndrome.
AB - Multiple studies have tried to establish the distinctive profile of individuals
with Asperger's syndrome (AS). However, recent reports suggest that adults with
AS feature heterogeneous cognitive profiles. The present study explores inter
individual variability in children with AS through group comparison and multiple
case series analysis. All participants completed an extended battery including
measures of fluid and crystallized intelligence, executive functions, theory of
mind, and classical neuropsychological tests. Significant group differences were
found in theory of mind and other domains related to global information
processing. However, the AS group showed high inter-individual variability (both
sub- and supra-normal performance) on most cognitive tasks. Furthermore, high
fluid intelligence correlated with less general cognitive impairment, high
cognitive flexibility, and speed of motor processing. In light of these findings,
we propose that children with AS are characterized by a distinct, uneven pattern
of cognitive strengths and weaknesses.
PMID- 25132814
TI - The ubiquitin-proteasome system in neurodegenerative diseases: precipitating
factor, yet part of the solution.
AB - The ubiquitin-proteasome system (UPS) has been implicated in neurodegenerative
diseases based on the presence of deposits consisting of ubiquitylated proteins
in affected neurons. It has been postulated that aggregation-prone proteins
associated with these disorders, such as alpha-synuclein, beta-amyloid peptide,
and polyglutamine proteins, compromise UPS function, and delay the degradation of
other proteasome substrates. Many of these substrates play important regulatory
roles in signaling, cell cycle progression, or apoptosis, and their inadvertent
stabilization due to an overloaded and improperly functioning UPS may thus be
responsible for cellular demise in neurodegeneration. Over the past decade,
numerous studies have addressed the UPS dysfunction hypothesis using various
model systems and techniques that differ in their readout and sensitivity. While
an inhibitory effect of some disease proteins on the UPS has been demonstrated,
increasing evidence attests that the UPS remains operative in many disease
models, which opens new possibilities for treatment. In this review, we will
discuss the paradigm shift that repositioned the UPS from being a prime suspect
in the pathophysiology of neurodegeneration to an attractive therapeutic target
that can be harnessed to accelerate the clearance of disease-linked proteins.
PMID- 25132818
TI - The neural architecture of age-related dual-task interferences.
AB - In daily life elderly adults exhibit deficits when dual-tasking is involved. So
far these deficits have been verified on a behavioral level in dual-tasking. Yet,
the neuronal architecture of these deficits in aging still remains to be explored
especially when late-middle aged individuals around 60 years of age are
concerned. Neuroimaging studies in young participants concerning dual-tasking
were, among others, related to activity in middle frontal (MFG) and superior
frontal gyrus (SFG) and the anterior insula (AI). According to the frontal lobe
hypothesis of aging, alterations in these frontal regions (i.e., SFG and MFG)
might be responsible for cognitive deficits. We measured brain activity using
fMRI, while examining age-dependent variations in dual-tasking by utilizing the
PRP (psychological refractory period) test. Behavioral data showed an increasing
PRP effect in late-middle aged adults. The results suggest the age-related
deteriorated performance in dual-tasking, especially in conditions of risen
complexity. These effects are related to changes in networks involving the AI,
the SFG and the MFG. The results suggest that different cognitive subprocesses
are affected that mediate the observed dual-tasking problems in late-middle aged
individuals.
PMID- 25132819
TI - Inhibiting lung lining fluid glutathione metabolism with GGsTop as a novel
treatment for asthma.
AB - Asthma is characterized by airway inflammation. Inflammation is associated with
oxidant stress. Airway epithelial cells are shielded from this stress by a thin
layer of lung lining fluid (LLF) which contains an abundance of the antioxidant
glutathione. LLF glutathione metabolism is regulated by gamma-glutamyl
transferase (GGT). Loss of LLF GGT activity in the mutant GGT(enu1) mouse causes
an increase in baseline LLF glutathione content which is magnified in an IL-13
model of allergic airway inflammation and protective against asthma. Normal mice
are susceptible to asthma in this model but can be protected with acivicin, a GGT
inhibitor. GGT is a target to treat asthma but acivicin toxicity limits clinical
use. GGsTop is a novel GGT inhibitor. GGsTop inhibits LLF GGT activity only when
delivered through the airway. In the IL-13 model, mice treated with IL-13 and
GGsTop exhibit a lung inflammatory response similar to that of mice treated with
IL-13 alone. But mice treated with IL-13 and GGsTop show attenuation of
methacholine-stimulated airway hyper-reactivity, inhibition of Muc5ac and Muc5b
gene induction, decreased airway epithelial cell mucous accumulation and a
fourfold increase in LLF glutathione content compared to mice treated with IL-13
alone. Mice treated with GGsTop alone are no different from that of mice treated
with saline alone, and show no signs of toxicity. GGsTop could represent a
valuable pharmacological tool to inhibit LLF GGT activity in pulmonary disease
models. The associated increase in LLF glutathione can protect lung airway
epithelial cells against oxidant injury associated with inflammation in asthma.
PMID- 25132822
TI - microRNA and skeletal muscle function: novel potential roles in exercise,
diseases, and aging.
PMID- 25132820
TI - Mitochondrial and cellular mechanisms for managing lipid excess.
AB - Current scientific debates center on the impact of lipids and mitochondrial
function on diverse aspects of human health, nutrition and disease, among them
the association of lipotoxicity with the onset of insulin resistance in skeletal
muscle, and with heart dysfunction in obesity and diabetes. Mitochondria play a
fundamental role in aging and in prevalent acute or chronic diseases. Lipids are
main mitochondrial fuels however these molecules can also behave as uncouplers
and inhibitors of oxidative phosphorylation. Knowledge about the functional
composition of these contradictory effects and their impact on mitochondrial
cellular energetics/redox status is incomplete. Cells store fatty acids (FAs) as
triacylglycerol and package them into cytoplasmic lipid droplets (LDs). New
emerging data shows the LD as a highly dynamic storage pool of FAs that can be
used for energy reserve. Lipid excess packaging into LDs can be seen as an
adaptive response to fulfilling energy supply without hindering mitochondrial or
cellular redox status and keeping low concentration of lipotoxic intermediates.
Herein we review the mechanisms of action and utilization of lipids by
mitochondria reported in liver, heart and skeletal muscle under relevant
physiological situations, e.g., exercise. We report on perilipins, a family of
proteins that associate with LDs in response to loading of cells with lipids.
Evidence showing that in addition to physical contact, mitochondria and LDs
exhibit metabolic interactions is presented and discussed. A hypothetical model
of channeled lipid utilization by mitochondria is proposed. Direct delivery and
channeled processing of lipids in mitochondria could represent a reliable and
efficient way to maintain reactive oxygen species (ROS) within levels compatible
with signaling while ensuring robust and reliable energy supply.
PMID- 25132824
TI - How Traumatic Experiences Leave Their Signature on the Genome: An Overview of
Epigenetic Pathways in PTSD.
PMID- 25132821
TI - Functional insights into modulation of BKCa channel activity to alter myometrial
contractility.
AB - The large-conductance voltage- and Ca(2+)-activated K(+) channel (BKCa) is an
important regulator of membrane excitability in a wide variety of cells and
tissues. In myometrial smooth muscle, activation of BKCa plays essential roles in
buffering contractility to maintain uterine quiescence during pregnancy and in
the transition to a more contractile state at the onset of labor. Multiple
mechanisms of modulation have been described to alter BKCa channel activity,
expression, and cellular localization. In the myometrium, BKCa is regulated by
alternative splicing, protein targeting to the plasma membrane, compartmentation
in membrane microdomains, and posttranslational modifications. In addition,
interaction with auxiliary proteins (i.e., beta1- and beta2-subunits),
association with G-protein coupled receptor signaling pathways, such as those
activated by adrenergic and oxytocin receptors, and hormonal regulation provide
further mechanisms of variable modulation of BKCa channel function in myometrial
smooth muscle. Here, we provide an overview of these mechanisms of BKCa channel
modulation and provide a context for them in relation to myometrial function.
PMID- 25132825
TI - Morphometric differences in planum temporale in schizophrenia and bipolar
disorder revealed by statistical analysis of labeled cortical depth maps.
AB - Differences in cortical thickness in the lateral temporal lobe, including the
planum temporale (PT), have been reported in MRI studies of schizophrenia (SCZ)
and bipolar disorder (BPD) patients. Most of these studies have used a single
valued global or local measure for thickness. However, additional and
complementary information can be obtained by generating labeled cortical distance
maps (LCDMs), which are distances of labeled gray matter (GM) voxels from the
nearest point on the GM/white matter (WM) (inner) cortical surface. Statistical
analyses of pooled and censored LCDM distances reveal subtle differences in PT
between SCZ and BPD groups from data generated by Ratnanather et al.
(Schizophrenia Research, http://dx.doi.org/10.1016/j.schres.2013.08.014). These
results confirm that the left planum temporale (LPT) is more sensitive than the
right PT in distinguishing between SCZ, BPD, and healthy controls. Also confirmed
is a strong gender effect, with a thicker PT seen in males than in females. The
differences between groups at smaller distances in the LPT revealed by pooled and
censored LCDM analysis suggest that SCZ and BPD have different effects on the
cortical mantle close to the GM/WM surface. This is consistent with reported
subtle changes in the cortical mantle observed in post-mortem studies.
PMID- 25132826
TI - Representational shifts made visible: movement away from the prototype in memory
for hue.
AB - In four experiments, a total of 205 participants studied individual color patches
and were given an old-new recognition test after a brief retention interval (0.5
or 5.0 s). The pattern of hue sensitivity (d') revealed hue memory shifting away
from the prototype of the hue's basic color category. The shifts demonstrate that
hue memory is influenced by categorization early in processing. The shifts did
not depend on intentional categorization; the shifts were found even when
participants made preference ratings at encoding rather than labeling judgments.
Overall, we found that categorization and memory are deeply intertwined from
perception onward. We discuss the impact of the results on theories of memory and
categorization, including the effects of category labels on memory (e.g., Lupyan,
2008). We also put forward the hypothesis that atypical shifts in hue are related
to atypical shifts that have previously observed in face recognition (Rhodes et
al., 1987).
PMID- 25132823
TI - Cannabinoid Regulation of Brain Reward Processing with an Emphasis on the Role of
CB1 Receptors: A Step Back into the Future.
AB - Over the last decades, the endocannabinoid system has been implicated in a large
variety of functions, including a crucial modulation of brain-reward circuits and
the regulation of motivational processes. Importantly, behavioral studies have
shown that cannabinoid compounds activate brain reward mechanisms and circuits in
a similar manner to other drugs of abuse, such as nicotine, alcohol, cocaine, and
heroin, although the conditions under which cannabinoids exert their rewarding
effects may be more limited. Furthermore, there is evidence on the involvement of
the endocannabinoid system in the regulation of cue- and drug-induced relapsing
phenomena in animal models. The aim of this review is to briefly present the
available data obtained using diverse behavioral experimental approaches in
experimental animals, namely, the intracranial self-stimulation paradigm, the
self-administration procedure, the conditioned place preference procedure, and
the reinstatement of drug-seeking behavior procedure, to provide a comprehensive
picture of the current status of what is known about the endocannabinoid system
mechanisms that underlie modification of brain-reward processes. Emphasis is
placed on the effects of cannabinoid 1 (CB1) receptor agonists, antagonists, and
endocannabinoid modulators. Further, the role of CB1 receptors in reward
processes is investigated through presentation of respective genetic ablation
studies in mice. The vast majority of studies in the existing literature suggest
that the endocannabinoid system plays a major role in modulating motivation and
reward processes. However, much remains to be done before we fully understand
these interactions. Further research in the future will shed more light on these
processes and, thus, could lead to the development of potential pharmacotherapies
designed to treat reward-dysfunction-related disorders.
PMID- 25132828
TI - An analysis of post-vocalic /s-?/ neutralization in Augsburg German: evidence for
a gradient sound change.
AB - The study is concerned with a sound change in progress by which a post-vocalic,
pre-consonantal /s-?/ contrast in the standard variety of German (SG) in words
such as west/wascht (/vEst/~/vE?t/, west/washes) is influencing the Augsburg
German (AG) variety in which they have been hitherto neutralized as /ve?t/. Two
of the main issues to be considered are whether the change is necessarily
categorical; and the extent to which the change affects both speech production
and perception equally. For the production experiment, younger and older AG and
SG speakers merged syllables of hypothetical town names to create a blend at the
potential neutralization site. These results showed a trend for a progressively
greater /s-?/ differentiation in the order older AG, younger AG, and SG speakers.
For the perception experiment, forced-choice responses were obtained from the
same subjects who had participated in the production experiment to a 16-step /s
?/ continuum that was embedded into two contexts: /mIst-mI?t/ in which /s-?/ are
neutralized in AG and /ve'mIse/-/ve'mI?e/ in which they are not. The results from
both experiments are indicative of a sound change in progress such that the
neutralization is being undone under the influence of SG, but in such a way that
there is a gradual shift between categories. The closer approximation of the
groups on perception suggests that the sound change may be more advanced on this
modality than in production. Overall, the findings are consistent with the idea
that phonological contrasts are experience-based, i.e., a continuous function of
the extent to which a subject is exposed to, and makes use of, the distinction
and are thus compatible with exemplar models of speech.
PMID- 25132829
TI - Contrasting group analysis of Brazilian students with dyslexia and good readers
using the computerized reading and writing assessment battery "BALE".
AB - The analysis of cognitive processes underpinning reading and writing skills may
help to distinguish different reading ability profiles. The present study used a
Brazilian reading and writing battery to compare performance of students with
dyslexia with two individually matched control groups: one contrasting on reading
competence but not age and the other group contrasting on age but not reading
competence. Participants were 28 individuals with dyslexia (19 boys) with a mean
age of 9.82 (SD +/- 1.44) drawn from public and private schools. These were
matched to: (1) an age control group (AC) of 26 good readers with a mean age of
9.77 (SD +/- 1.44) matched by age, sex, years of schooling, and type of school;
(2) reading control group (RC) of 28 younger controls with a mean age of 7.82 (SD
+/- 1.06) matched by sex, type of school, and reading level. All groups were
tested on four tasks from the Brazilian Reading and Writing Assessment battery
("BALE"): Written Sentence Comprehension Test (WSCT); Spoken Sentence
Comprehension Test (OSCT); Picture-Print Writing Test (PPWT 1.1-Writing); and the
Reading Competence Test (RCT). These tasks evaluate reading and listening
comprehension for sentences, spelling, and reading isolated words and pseudowords
(non-words). The dyslexia group scored lower and took longer to complete tasks
than the AC group. Compared with the RC group, there were no differences in total
scores on reading or oral comprehension tasks. However, dyslexics presented
slower reading speeds, longer completion times, and lower scores on spelling
tasks, even compared with younger controls. Analysis of types of errors on word
and pseudoword reading items showed students with dyslexia scoring lower for
pseudoword reading than the other two groups. These findings suggest that the
dyslexics overall scores were similar to those of younger readers. However,
specific phonological and visual decoding deficits showed that the two groups
differ in terms of underpinning reading strategies.
PMID- 25132827
TI - Toward a dual-learning systems model of speech category learning.
AB - More than two decades of work in vision posits the existence of dual-learning
systems of category learning. The reflective system uses working memory to
develop and test rules for classifying in an explicit fashion, while the
reflexive system operates by implicitly associating perception with actions that
lead to reinforcement. Dual-learning systems models hypothesize that in learning
natural categories, learners initially use the reflective system and, with
practice, transfer control to the reflexive system. The role of reflective and
reflexive systems in auditory category learning and more specifically in speech
category learning has not been systematically examined. In this article, we
describe a neurobiologically constrained dual-learning systems theoretical
framework that is currently being developed in speech category learning and
review recent applications of this framework. Using behavioral and computational
modeling approaches, we provide evidence that speech category learning is
predominantly mediated by the reflexive learning system. In one application, we
explore the effects of normal aging on non-speech and speech category learning.
Prominently, we find a large age-related deficit in speech learning. The
computational modeling suggests that older adults are less likely to transition
from simple, reflective, unidimensional rules to more complex, reflexive, multi
dimensional rules. In a second application, we summarize a recent study examining
auditory category learning in individuals with elevated depressive symptoms. We
find a deficit in reflective-optimal and an enhancement in reflexive-optimal
auditory category learning. Interestingly, individuals with elevated depressive
symptoms also show an advantage in learning speech categories. We end with a
brief summary and description of a number of future directions.
PMID- 25132830
TI - Cognition-emotion interactions: patterns of change and implications for math
problem solving.
AB - Surprisingly little is known about whether relationships between cognitive and
emotional states remain stable or change over time, or how different patterns of
stability and/or change in the relationships affect problem solving abilities.
Nevertheless, cross-sectional studies show that anxiety/worry may reduce working
memory (WM) resources, and the ability to minimize the effects anxiety/worry is
higher in individuals with greater WM capacity. To investigate the patterns of
stability and/or change in cognition-emotion relations over time and their
implications for problem solving, 126 14-year-olds' algebraic WM and worry levels
were assessed twice in a single day before completing an algebraic math problem
solving test. We used latent transition analysis to identify stability/change in
cognition-emotion relations, which yielded a six subgroup solution. Subgroups
varied in WM capacity, worry, and stability/change relationships. Among the
subgroups, we identified a high WM/low worry subgroup that remained stable over
time and a high WM/high worry, and a moderate WM/low worry subgroup that changed
to low WM subgroups over time. Patterns of stability/change in subgroup
membership predicted algebraic test results. The stable high WM/low worry
subgroup performed best and the low WM capacity-high worry "unstable across time"
subgroup performed worst. The findings highlight the importance of assessing
variations in cognition-emotion relationships over time (rather than assessing
cognition or emotion states alone) to account for differences in problem solving
abilities.
PMID- 25132831
TI - Medical management of hereditary optic neuropathies.
AB - Hereditary optic neuropathies are diseases affecting the optic nerve. The most
common are mitochondrial hereditary optic neuropathies, i.e., the maternally
inherited Leber's hereditary optic neuropathy (LHON) and dominant optic atrophy
(DOA). They both share a mitochondrial pathogenesis that leads to the selective
loss of retinal ganglion cells and axons, in particular of the papillo-macular
bundle. Typically, LHON is characterized by an acute/subacute loss of central
vision associated with impairment of color vision and swelling of retinal nerve
fibers followed by optic atrophy. DOA, instead, is characterized by a childhood
onset and slowly progressive loss of central vision, worsening over the years,
leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic
evaluation and genetic testing of the three most common mitochondrial DNA
mutations affecting complex I (11778/ND4, 3460/ND1, and 14484/ND6) for LHON and
sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are still
limited including agents that bypass the complex I defect and exert an
antioxidant effect (idebenone). Further strategies are aimed at stimulating
compensatory mitochondrial biogenesis. Gene therapy is also a promising avenue
that still needs to be validated.
PMID- 25132832
TI - Biosphere frontiers of subsurface life in the sedimented hydrothermal system of
Guaymas Basin.
AB - Temperature is one of the key constraints on the spatial extent, physiological
and phylogenetic diversity, and biogeochemical function of subsurface life. A
model system to explore these interrelationships should offer a suitable range of
geochemical regimes, carbon substrates and temperature gradients under which
microbial life can generate energy and sustain itself. In this theory and
hypothesis article, we make the case for the hydrothermally heated sediments of
Guaymas Basin in the Gulf of California as a suitable model system where
extensive temperature and geochemical gradients create distinct niches for active
microbial populations in the hydrothermally influenced sedimentary subsurface
that in turn intercept and process hydrothermally generated carbon sources. We
synthesize the evidence for high-temperature microbial methane cycling and
sulfate reduction at Guaymas Basin - with an eye on sulfate-dependent oxidation
of abundant alkanes - and demonstrate the energetic feasibility of these latter
types of deep subsurface life in previously drilled Guaymas Basin locations of
Deep-Sea Drilling Project 64.
PMID- 25132834
TI - Imposition of encapsulated non-indigenous probiotics into intestine may disturb
human core microbiome.
PMID- 25132833
TI - Aspergillus flavus infection induces transcriptional and physical changes in
developing maize kernels.
AB - Maize kernels are susceptible to infection by the opportunistic pathogen
Aspergillus flavus. Infection results in reduction of grain quality and
contamination of kernels with the highly carcinogenic mycotoxin, aflatoxin. To
understanding host response to infection by the fungus, transcription of
approximately 9000 maize genes were monitored during the host-pathogen
interaction with a custom designed Affymetrix GeneChip(r) DNA array. More than
4000 maize genes were found differentially expressed at a FDR of 0.05. This
included the up regulation of defense related genes and signaling pathways.
Transcriptional changes also were observed in primary metabolism genes. Starch
biosynthetic genes were down regulated during infection, while genes encoding
maize hydrolytic enzymes, presumably involved in the degradation of host
reserves, were up regulated. These data indicate that infection of the maize
kernel by A. flavus induced metabolic changes in the kernel, including the
production of a defense response, as well as a disruption in kernel development.
PMID- 25132837
TI - A complex immunological idiotypic network for maintenance of tolerance.
PMID- 25132835
TI - Insights into the Relationship between Toll Like Receptors and Gamma Delta T Cell
Responses.
AB - The tumor microenvironment is an important aspect of cancer biology that
contributes to tumor initiation, tumor progression and responses to therapy. The
composition and characteristics of the tumor microenvironment vary widely and are
important in determining the anti-tumor immune response. Successful immunization
requires activation of both innate and adaptive immunity. Generally, immune
system is compromised in patients with cancer due to immune suppression, loss of
tumor antigen expression and dysfunction of antigen presenting cells (APC). Thus,
therapeutic immunization leading to cancer regression remains a significant
challenge. Certain cells of the immune system, including dendritic cells (DCs)
and gamma delta (gammadelta) T cells are capable of driving potent anti-tumor
responses. The property of MHC-unrestricted cytotoxicity, high potential of
cytokine release, tissue tropism and early activation in infections and malignant
disease makes gammadelta T cells as an emerging candidate for immunotherapy.
Various strategies are being developed to enhance anti-tumor immune responses of
gammadelta T cells and DCs one of them is the use of novel adjuvants like toll
like receptors (TLR) agonists, which enhance gammadelta T cell function directly
or through DC activation, which has ability to prime gammadelta T cells. TLR
agonists are being used clinically either alone or in combination with tumor
antigens and has shown initial success in both enhancing immune responses and
eliciting anti-tumor activity. TLR activated gammadelta T cells and DCs nurture
each other's activation. This provides a potent base for first line of defense
and manipulation of the adaptive response against pathogens and cancer. The
available data provides a strong rationale for initiating combinatorial therapy
for the treatment of diseases and this review will summarize the application of
adjuvants (TLRs) for boosting immune response of gammadelta T cells to treat
cancer and infectious diseases and their use in combinatorial therapy.
PMID- 25132836
TI - Toll-Like Receptors and Cancer: MYD88 Mutation and Inflammation.
AB - Pattern recognition receptors (PRRs) expressed on immune cells are crucial for
the early detection of invading pathogens, in initiating early innate immune
response and in orchestrating the adaptive immune response. PRRs are activated by
specific pathogen-associated molecular patterns that are present in pathogenic
microbes or nucleic acids of viruses or bacteria. However, inappropriate
activation of these PRRs, such as the Toll-like receptors (TLRs), due to genetic
lesions or chronic inflammation has been demonstrated to be a major cause of many
hematological malignancies. Gain-of-function mutations in the TLR adaptor protein
MYD88 found in 39% of the activated B cell type of diffuse large B cell lymphomas
and almost 100% of Waldenstrom's macroglobulinemia further highlight the
involvement of TLRs in these malignancies. MYD88 mutations result in the chronic
activation of TLR signaling pathways, thus the constitutive activation of the
transcription factor NFkappaB to promote cell survival and proliferation. These
recent insights into TLR pathway driven malignancies warrant the need for a
better understanding of TLRs in cancers and the development of novel anti-cancer
therapies targeting TLRs. This review focuses on TLR function and signaling in
normal or inflammatory conditions, and how mutations can hijack the TLR signaling
pathways to give rise to cancer. Finally, we discuss how potential therapeutic
agents could be used to restore normal responses to TLRs and have long lasting
anti-tumor effects.
PMID- 25132839
TI - Beyond grasses: the potential benefits of studying silicon accumulation in non
grass species.
PMID- 25132841
TI - Freedom in bioinformatics.
PMID- 25132840
TI - Exploring the function of protein kinases in schistosomes: perspectives from the
laboratory and from comparative genomics.
AB - Eukaryotic protein kinases are well conserved through evolution. The genome of
Schistosoma mansoni, which causes intestinal schistosomiasis, encodes over 250
putative protein kinases with all of the main eukaryotic groups represented.
However, unraveling functional roles for these kinases is a considerable
endeavor, particularly as protein kinases regulate multiple and sometimes
overlapping cell and tissue functions in organisms. In this article, elucidating
protein kinase signal transduction and function in schistosomes is considered
from the perspective of the state-of-the-art methodologies used and comparative
organismal biology, with a focus on current advances and future directions. Using
the free-living nematode Caenorhabditis elegans as a comparator we predict roles
for various schistosome protein kinases in processes vital for host invasion and
successful parasitism such as sensory behavior, growth and development. It is
anticipated that the characterization of schistosome protein kinases in the
context of parasite function will catalyze cutting edge research into host
parasite interactions and will reveal new targets for developing drug
interventions against human schistosomiasis.
PMID- 25132842
TI - Repair and regeneration properties of Ginkgo biloba after ischemic brain injury.
PMID- 25132843
TI - Automatic labeling of vertebral levels using a robust template-based approach.
AB - Context. MRI of the spinal cord provides a variety of biomarkers sensitive to
white matter integrity and neuronal function. Current processing methods are
based on manual labeling of vertebral levels, which is time consuming and prone
to user bias. Although several methods for automatic labeling have been
published; they are not robust towards image contrast or towards susceptibility
related artifacts. Methods. Intervertebral disks are detected from the 3D
analysis of the intensity profile along the spine. The robustness of the disk
detection is improved by using a template of vertebral distance, which was
generated from a training dataset. The developed method has been validated using
T1- and T2-weighted contrasts in ten healthy subjects and one patient with spinal
cord injury. Results. Accuracy of vertebral labeling was 100%. Mean absolute
error was 2.1 +/- 1.7 mm for T2-weighted images and 2.3 +/- 1.6 mm for T1
weighted images. The vertebrae of the spinal cord injured patient were correctly
labeled, despite the presence of artifacts caused by metallic implants.
Discussion. We proposed a template-based method for robust labeling of vertebral
levels along the whole spinal cord for T1- and T2-weighted contrasts. The method
is freely available as part of the spinal cord toolbox.
PMID- 25132844
TI - Nonreference medical image edge map measure.
AB - Edge detection is a key step in medical image processing. It is widely used to
extract features, perform segmentation, and further assist in diagnosis. A poor
quality edge map can result in false alarms and misses in cancer detection
algorithms. Therefore, it is necessary to have a reliable edge measure to assist
in selecting the optimal edge map. Existing reference based edge measures require
a ground truth edge map to evaluate the similarity between the generated edge map
and the ground truth. However, the ground truth images are not available for
medical images. Therefore, a nonreference edge measure is ideal for medical image
processing applications. In this paper, a nonreference reconstruction based edge
map evaluation (NREM) is proposed. The theoretical basis is that a good edge map
keeps the structure and details of the original image thus would yield a good
reconstructed image. The NREM is based on comparing the similarity between the
reconstructed image with the original image using this concept. The edge measure
is used for selecting the optimal edge detection algorithm and optimal parameters
for the algorithm. Experimental results show that the quantitative evaluations
given by the edge measure have good correlations with human visual analysis.
PMID- 25132838
TI - Leaf development: a cellular perspective.
AB - Through its photosynthetic capacity the leaf provides the basis for growth of the
whole plant. In order to improve crops for higher productivity and resistance for
future climate scenarios, it is important to obtain a mechanistic understanding
of leaf growth and development and the effect of genetic and environmental
factors on the process. Cells are both the basic building blocks of the leaf and
the regulatory units that integrate genetic and environmental information into
the developmental program. Therefore, to fundamentally understand leaf
development, one needs to be able to reconstruct the developmental pathway of
individual cells (and their progeny) from the stem cell niche to their final
position in the mature leaf. To build the basis for such understanding, we review
current knowledge on the spatial and temporal regulation mechanisms operating on
cells, contributing to the formation of a leaf. We focus on the molecular
networks that control exit from stem cell fate, leaf initiation, polarity,
cytoplasmic growth, cell division, endoreduplication, transition between division
and expansion, expansion and differentiation and their regulation by
intercellular signaling molecules, including plant hormones, sugars, peptides,
proteins, and microRNAs. We discuss to what extent the knowledge available in the
literature is suitable to be applied in systems biology approaches to model the
process of leaf growth, in order to better understand and predict leaf growth
starting with the model species Arabidopsis thaliana.
PMID- 25132845
TI - Neural networks and fault probability evaluation for diagnosis issues.
AB - This paper presents a new FDI technique for fault detection and isolation in
unknown nonlinear systems. The objective of the research is to construct and
analyze residuals by means of artificial intelligence and probabilistic methods.
Artificial neural networks are first used for modeling issues. Neural networks
models are designed for learning the fault-free and the faulty behaviors of the
considered systems. Once the residuals generated, an evaluation using
probabilistic criteria is applied to them to determine what is the most likely
fault among a set of candidate faults. The study also includes a comparison
between the contributions of these tools and their limitations, particularly
through the establishment of quantitative indicators to assess their performance.
According to the computation of a confidence factor, the proposed method is
suitable to evaluate the reliability of the FDI decision. The approach is applied
to detect and isolate 19 fault candidates in the DAMADICS benchmark. The results
obtained with the proposed scheme are compared with the results obtained
according to a usual thresholding method.
PMID- 25132847
TI - The incidence and risk factors for lower limb skin graft failure.
AB - Lower limb skin grafts are thought to have higher failure rates than skin grafts
in other sites of the body. Currently, there is a paucity of literature on
specific factors associated with lower limb skin graft failure. We present a
series of 70 lower limb skin grafts in 50 patients with outcomes at 6 weeks. One
third of lower limb skin grafts went on to fail with increased BMI, peripheral
vascular disease, and immunosuppressant medication use identified as significant
risk factors.
PMID- 25132846
TI - Cosmetic contact sensitivity in patients with melasma: results of a pilot study.
AB - Background. Some of the patients with melasma perhaps have pigmented cosmetic
dermatitis. However, cosmetic contact sensitivity in melasma remains poorly
studied particularly in the Indian context. Objectives. To study cosmetic contact
sensitivity in patients with melasma. Materials and Methods. 67 (F : M = 55 : 12)
consecutive patients with melasma between 19 and 49 years of age were patch
tested sequentially during January-December, 2012, with Indian Cosmetic and
Fragrance Series, Indian Sunscreen Series, p-phenylenediamine, and patient's own
cosmetic products. Results. 52 (78%) patients were in the age group of 20-40
years. The duration of melasma varied from 1 month to 20 years. Centrofacial,
malar, and mandibular patterns were observed in 48 (72%), 18 (27%), and 1 (1%)
patients, respectively. Indian Cosmetics and Fragrance Series elicited positive
reactions in 29 (43.3%) patients. Cetrimide was the most common contact
sensitizers eliciting positivity in 15 (52%) patients, followed by gallate mix in
9 (31%) patients and thiomersal in 7 (24%) patients. Only 2 of the 42 patients
showed positive reaction from their own cosmetics while the other 5 patients had
irritant reaction. Indian Sunscreen Series did not elicit any positive reaction.
Conclusion. Cosmetics contact sensitivity appears as an important cause of
melasma not associated with pregnancy, lactation, or hormone therapy.
PMID- 25132848
TI - Online medicine for pregnant women.
AB - Objective. To assess the use of cell phones and email as means of communication
between pregnant women and their gynecologists and family physicians. Study
Design. A cross-sectional study of pregnant women at routine followup. One
hundred and twenty women participated in the study. Results. The mean age was
27.4 +/- 3.4 years. One hundred nineteen women owned a cell phone and 114 (95%)
had an email address. Seventy-two women (60%) had their gynecologist's cell phone
number and 50 women (42%) had their family physician's cell phone number. More
women contacted their gynecologist via cell phone or email during pregnancy
compared to their family physician (P = 0.005 and 0.009, resp.). Most preferred
to communicate with their physician via cell phone at predetermined times, but by
email at any time during the day (P < 0.0001). They would use cell phones for
emergencies or unusual problems but preferred email for other matters (P <
0.0001). Conclusions. Pregnant women in the Negev region do not have a preference
between the use of cell phones or email for medical consultation with their
gynecologist or family physician. The provision of the physician's cell phone
numbers or email address together with the provision of guidelines and resources
could improve healthcare services.
PMID- 25132849
TI - IN-MACA-MCC: Integrated Multiple Attractor Cellular Automata with Modified Clonal
Classifier for Human Protein Coding and Promoter Prediction.
AB - Protein coding and promoter region predictions are very important challenges of
bioinformatics (Attwood and Teresa, 2000). The identification of these regions
plays a crucial role in understanding the genes. Many novel computational and
mathematical methods are introduced as well as existing methods that are getting
refined for predicting both of the regions separately; still there is a scope for
improvement. We propose a classifier that is built with MACA (multiple attractor
cellular automata) and MCC (modified clonal classifier) to predict both regions
with a single classifier. The proposed classifier is trained and tested with
Fickett and Tung (1992) datasets for protein coding region prediction for DNA
sequences of lengths 54, 108, and 162. This classifier is trained and tested with
MMCRI datasets for protein coding region prediction for DNA sequences of lengths
252 and 354. The proposed classifier is trained and tested with promoter
sequences from DBTSS (Yamashita et al., 2006) dataset and nonpromoters from EID
(Saxonov et al., 2000) and UTRdb (Pesole et al., 2002) datasets. The proposed
model can predict both regions with an average accuracy of 90.5% for promoter and
89.6% for protein coding region predictions. The specificity and sensitivity
values of promoter and protein coding region predictions are 0.89 and 0.92,
respectively.
PMID- 25132850
TI - Analysis and Determination of Trace Metals (Nickel, Cadmium, Chromium, and Lead)
in Tissues of Pampus argenteus and Platycephalus indicus in the Hara Reserve,
Iran.
AB - The accumulations of Cd, Ni, Pb, and Cr were measured in muscle, gill, kidney,
and liver of Platycephalus indicus and Pampus argenteus. Our results indicated
that all metals were found to be the highest in tissues in P. indicus (benthic
species). Except Ni in P. indicus, concentrations of metals and bioaccumulation
factor were in the following sequence: liver > kidney > gill > muscle. The data
revealed that there is a significant negative correlation between concentrations
of metals and size and age factors. The Ni and Cr levels in the muscles were
higher than the maximum acceptable limit recommended by WHO and FEPA. Similarly,
the concentration of Pb measured in P. indicus muscle exceeded the FAO standard
limit.
PMID- 25132851
TI - Laparoscopic adrenalectomy for adrenal tumors.
AB - Objective. To evaluate the indication and the clinical value of laparoscopic
adrenalectomy of different types of adrenal tumor. Methods. From 2009 to 2014, a
total of 110 patients were diagnosed with adrenal benign tumor by CT scan and we
performed laparoscopic adrenalectomy. The laparoscopic approach has been the
procedure of choice for surgery of benign adrenal tumors, and the upper limit of
tumor size was thought to be 6 cm. Results. 109 of 110 cases were successful;
only one was converted to open surgery due to bleeding. The average operating
time and intraoperative blood loss of pheochromocytoma were significantly more
than the benign tumors (P < 0.05). After 3 months of follow-up, the preoperative
symptoms were relieved and there was no recurrence. Conclusions. Laparoscopic
adrenalectomy has the advantages of minimal invasion, less blood loss, fewer
complications, quicker recovery, and shorter hospital stay. The full preparation
before operation can decrease the average operating time and intraoperative blood
loss of pheochromocytomas. Laparoscopic adrenalectomy should be considered as the
first choice treatment for the resection of adrenal benign tumor.
PMID- 25132852
TI - MTNR1B Genetic Variability Is Associated with Gestational Diabetes in Czech
Women.
AB - The gene MTNR1B encodes a receptor for melatonin. Melatonin receptors are
expressed in human beta-cells, which implies that genetic variants might affect
glucose tolerance. Meta-analysis confirmed that the rs10830963 shows the most
robust association. The aim of the study was to assess the rs10830963 in Czech
GDM patients and controls and to study relations between the SNP and biochemical
as well as anthropometric characteristics. Our cohort consisted of 880 women; 458
were diagnosed with GDM, and 422 were normoglycemic controls without history of
GDM. Despite similar BMI, the GDM group showed higher WHR, waist circumference,
abdominal circumference, and total body fat content. The risk allele G was more
frequent in the GDM group (38.3 versus 29.4% in controls, OR 1.49 CI95% [1.22;
1.82]; P OR = 0.0001). In spite of higher frequency, the G allele in the GDM
group was not associated with any markers of glucose metabolism. In contrast,
controls showed significant association of the allele G with FPG and with
postchallenge glycemia during the oGTT. Frequency analysis indicates that
rs10830963 is involved in gestational diabetes in Czech women. However, the
association of the SNP with glucose metabolism, which is obvious in controls, is
covert in women who have experienced GDM.
PMID- 25132853
TI - FBP1 Is an Interacting Partner of Menin.
AB - Multiple endocrine neoplasia type 1 (MEN1) is a syndrome characterized by tumors
in multiple endocrine tissues such as the parathyroid glands, the pituitary
gland, and the enteropancreatic neuroendocrine tissues. MEN1 is usually caused by
mutations in the MEN1 gene that codes for the protein menin. Menin interacts with
proteins that regulate transcription, DNA repair and processing, and maintenance
of cytoskeletal structure. We describe the identification of FBP1 as an
interacting partner of menin in a large-scale pull-down assay that also
immunoprecipitated RBBP5, ASH2, and LEDGF, which are members of complex proteins
associated with SET1 (COMPASS), a protein complex that methylates histone H3.
This interaction was confirmed by coimmunoprecipitation and Flag-pull-down
assays. Furthermore, menin localized to the FUSE site on the MYC promoter, a site
that is transactivated by FBP1. This investigation therefore places menin in a
pathway that regulates MYC gene expression and has important implications for the
biological function of menin.
PMID- 25132854
TI - Fasting hyperglycemia increases in-hospital mortality risk in nondiabetic female
patients with acute myocardial infarction: a retrospective study.
AB - Previous studies had shown that elevated admission plasma glucose (APG) could
increase mortality rate and serious complications of acute myocardial infarction
(AMI), but whether fasting plasma glucose (FPG) had the same role remains
controversial. In this retrospective study, 253 cases of AMI patients were
divided into diabetic (n = 87) and nondiabetic group (n = 166). Our results
showed that: compared with the nondiabetic patients, diabetic patients had higher
APG, FPG, higher plasma triglyceride, higher rates of painless AMI (P < 0.01),
non-ST-segment elevation myocardial infarction (NSTEMI), and reinfraction (P <
0.05). They also had lower high density lipoprotein cholesterol and rate of
malignant arrhythmia, but in-hospital mortality rate did not differ significantly
(P > 0.05). While nondiabetic patients were subgrouped in terms of APG and FPG
(cut points were 11.1 mmol/L and 7.0 mmol/L, resp.), the mortality rate had
significant difference (P < 0.01), whereas glucose level lost significance in
diabetic group. Multivariate logistic regression analysis showed that FPG (OR:
2.014; 95% confidence interval: 1.296-3.131; p < 0.01) but not APG was
independent predictor of in-hospital mortality for nondiabetic patients. These
results indicate that FPG can be an independent predictor for mortality in
nondiabetic female patients with AMI.
PMID- 25132855
TI - Radiological assessment of the Indian children with congenital sensorineural
hearing loss.
AB - Introduction. Congenital sensorineural hearing loss is one of the most common
birth defects with incidence of approximately 1 : 1000 live births. Imaging of
cases of congenital sensorineural hearing loss is frequently performed in an
attempt to determine the underlying pathology. There is a paucity of literature
from India and for this reason we decided to conduct this study in Indian context
to evaluate the various cochleovestibular bony and nerve anomalies by HRCT scan
of temporal bone and MRI with 3D scan of inner ear in a tertiary care centre.
Material and Methods. A total of 280 children with congenital deafness (158 males
and 122 females), between January 2002 to June 2013 were included in the study
and they were assessed radiologically by HRCT scan of temporal bone and MRI with
3D scan of inner ear. Results. In the present study we found various congenital
anomalies of bony labyrinth and vestibulocochlear nerve. Out of 560 inner ears we
found 78 anomalous inner ears. Out of these 78 inner ears 57 (73%) had cochlear
anomaly, 68 (87.1%) had anomalous vestibule, 44 (56.4%) had abnormal vestibular
aqueduct, 24 (30.7%) had anomalous IAC, and 23 (29.4%) had abnormal
cochleovestibular nerves. Conclusion. In present study, we found lower incidences
of congenital anomalies comparative to existing literature.
PMID- 25132857
TI - The Secretome of Bone Marrow and Wharton Jelly Derived Mesenchymal Stem Cells
Induces Differentiation and Neurite Outgrowth in SH-SY5Y Cells.
AB - The goal of this study was to determine and compare the effects of the secretome
of mesenchymal stem cells (MSCs) isolated from human bone-marrow (BMSCs) and the
Wharton jelly surrounding the vein and arteries of the umbilical cord (human
umbilical cord perivascular cells (HUCPVCs)) on the survival and differentiation
of a human neuroblastoma cell line (SH-SY5Y). For this purpose, SH-SY5Y cells
were differentiated with conditioned media (CM) from the MSCs populations
referred above. Retinoic acid cultured cells were used as control for neuronal
differentiated SH-SY5Y cells. SH-SY5Y cells viability assessment revealed that
the secretome of BMSCs and HUCPVCs, in the form of CM, was able to induce their
survival. Moreover, immunocytochemical experiments showed that CM from both MSCs
was capable of inducing neuronal differentiation of SH-SY5Y cells. Finally,
neurite lengths assessment and quantitative real-time reverse-transcription
polymerase chain reaction (RT-PCR) analysis demonstrated that CM from BMSCs and
HUCPVCs differently induced neurite outgrowth and mRNA levels of neuronal markers
exhibited by SH-SY5Y cells. Overall, our results show that the secretome of both
BMSCs and HUCPVCs was capable of supporting SH-SY5Y cells survival and promoting
their differentiation towards a neuronal phenotype.
PMID- 25132858
TI - Wrist-ankle acupuncture for the treatment of pain symptoms: a systematic review
and meta-analysis.
AB - Routine acupuncture incorporates wrist-ankle acupuncture (WAA) for its analgesic
effect, but WAA is not widely used in clinics due to incomplete knowledge of its
effectiveness and concerns about less clinical research and because less people
know it. This study aimed to assess the efficacy and possible adverse effects of
WAA or WAA adjuvants in the treatment of pain symptoms. This study compared WAA
or WAA adjuvant with the following therapies: western medication (WM), sham
acupuncture (SA), or body acupuncture (BA). Randomized controlled trials (RCTs)
were searched systematically in related electronic databases by two independent
reviewers. 33 RCTs were finally included, in which 7 RCTs were selected for meta
analysis. It was found that WAA or WAA adjuvant was significantly more effective
than WM, SA, or BA in pain relief. There was nothing different between WAA and SA
in adverse events, but WAA was marginally significantly safer than WM. Although
both WAA and WAA adjuvant appeared to be more effective than WM, SA, or BA in the
treatment of pain symptoms with few side effects, further studies with better and
more rigorously designed are still necessary to ensure the efficacy and safety
issue of WAA due to the poor methodology and small sample size of previous
studies.
PMID- 25132856
TI - Management of fibrosis: the mesenchymal stromal cells breakthrough.
AB - Fibrosis is the endpoint of many chronic inflammatory diseases and is defined by
an abnormal accumulation of extracellular matrix components. Despite its slow
progression, it leads to organ malfunction. Fibrosis can affect almost any
tissue. Due to its high frequency, in particular in the heart, lungs, liver, and
kidneys, many studies have been conducted to find satisfactory treatments.
Despite these efforts, current fibrosis management therapies either are
insufficiently effective or induce severe adverse effects. In the light of these
facts, innovative experimental therapies are being investigated. Among these,
cell therapy is regarded as one of the best candidates. In particular,
mesenchymal stromal cells (MSCs) have great potential in the treatment of
inflammatory diseases. The value of their immunomodulatory effects and their
ability to act on profibrotic factors such as oxidative stress, hypoxia, and the
transforming growth factor-beta1 pathway has already been highlighted in
preclinical and clinical studies. Furthermore, their propensity to act depending
on the microenvironment surrounding them enhances their curative properties. In
this paper, we review a large range of studies addressing the use of MSCs in the
treatment of fibrotic diseases. The results reported here suggest that MSCs have
antifibrotic potential for several organs.
PMID- 25132859
TI - Syndrome Differentiation of Diabetes by the Traditional Chinese Medicine
according to Evidence-Based Medicine and Expert Consensus Opinion.
AB - In Chinese medicine, diabetes belongs to the category of "Xiaoke disease (disease
with symptoms of frequent drinking and urination)"; in the traditional sense, its
pathogenesis is "Yin deficiency and dryness-heat." However, over time, changes in
the social environment and lifestyle have also changed the use of traditional
Chinese medicine (TCM) in diabetes. In this study, we performed diabetes syndrome
differentiation using TCM according to evidence-based medicine and expert
consensus opinion.
PMID- 25132860
TI - IKK beta -Targeted Anti-Inflammatory Activities of a Butanol Fraction of
Artificially Cultivated Cordyceps pruinosa Fruit Bodies.
AB - The inhibitory activities of the Cordyceps pruinosa butanol fraction (Cp-BF) were
investigated by determining inflammatory responses of lipopolysaccharide (LPS)
treated RAW264.7 macrophage cells and by evaluating HCl/ethanol (EtOH)-triggered
gastric ulcers in mice. The molecular mechanisms of the inhibitory effects of Cp
BF were investigated by identifying target enzymes using biochemical and
molecular biological approaches. Cp-BF strongly inhibited the production of NO
and TNF-alpha, release of reactive oxygen species (ROS), phagocytic uptake of
FITC-dextran, and mRNA expression levels of interleukin (IL)-6, inducible NO
synthase (iNOS), and tumour necrosis factor-alpha (TNF)-alpha in activated
RAW264.7 cells. Cp-BF also strongly downregulated the NF-kappaB pathway by
suppressing IKKbeta according to luciferase reporter assays and immunoblot
analysis. Furthermore, Cp-BF blocked both increased levels of NF-kappaB-mediated
luciferase activities and phosphorylation of p65/p50 observed by IKKbeta
overexpression. Finally, orally administered Cp-BF was found to attenuate gastric
ulcer and block the phosphorylation of IkappaBalpha induced by HCl/EtOH.
Therefore, these results suggest that the anti-inflammatory activity of Cp-BF may
be mediated by suppression of IKKalpha and its downstream NF-kappaB activation.
Since our group has established the mass cultivation conditions by developing
culture conditions for Cordyceps pruinosa, the information presented in this
study may be useful for developing new anti-inflammatory agents.
PMID- 25132861
TI - Effect of ST36 Acupuncture on Hyperventilation-Induced CO 2 Reactivity of the
Basilar and Middle Cerebral Arteries and Heart Rate Variability in Normal
Subjects.
AB - This study was conducted to verify the effect of acupuncture on cerebral
haemodynamics to provide evidence for the use of acupuncture treatment as a
complementary therapy for the high-risk stroke population. The effect of ST36
acupuncture treatment on the hyperventilation-induced CO2 reactivity of the
basilar and middle cerebral arteries was studied in 10 healthy male volunteers
(mean age, 25.2 +/- 1.5 years) using a transcranial Doppler sonography with an
interval of 1 week between measurements, and a portable ECG monitoring system was
used to obtain ECG data simultaneously. The CO2 reactivity of the basilar and
middle cerebral arteries increased significantly after ST36 acupuncture
treatment, whereas the mean arterial blood pressure and pulse rate did not change
significantly. The high-frequency power significantly increased after ST36
acupuncture treatment, and the percentage increase of high-frequency power
correlated significantly with the percentage increase in the CO2 reactivity of
the contralateral middle cerebral artery. These data suggest that ST36
acupuncture treatment increases CO2 reactivity, indicating improvement of
vasodilatory potential of the cerebral vasculature to compensate for fluctuations
caused by changes in external conditions. The increase in parasympathetic tone by
ST36 acupuncture treatment is responsible for this therapeutic effect.
PMID- 25132863
TI - A note regarding problems with interaction and varying block sizes in a
comparison of endotracheal tubes.
AB - A randomized clinical experiment to compare two types of endotracheal tubes
utilized a block design where each of the six participating anesthesiologists
performed tube insertions for an equal number of patients for each type of tube.
Five anesthesiologists intubated at least three patients with each tube type, but
one anesthesiologist intubated only one patient per tube type. Overall, one type
of tube outperformed the other on all three effectiveness measures. However,
analysis of the data using an interaction model gave conflicting and misleading
results, making the tube with the better performance appear to perform worse.
This surprising result was caused by the undue influence of the data for the
anesthesiologist who intubated only two patients. We therefore urge caution in
interpreting results from interaction models with designs containing small
blocks.
PMID- 25132864
TI - A necessary evil? Intra-abdominal hypertension complicating burn patient
resuscitation.
AB - OBJECTIVE: Severe burns are devastating injuries that result in considerable
systemic inflammation and often require resuscitation with large volumes of
fluid. The result of massive resuscitation is often raised intra-abdominal
pressures leading to Intra-abdominal hypertension (IAH) and the secondary
abdominal compartment syndrome. The objective of this study is to conduct (1) a
10 year retrospective study to investigate epidemiological factors contributing
to burn injuries in Alberta, (2) to characterize fluid management and incidence
of IAH and ACS and (3) to review fluid resuscitation with a goal to identify
optimal strategies for fluid resuscitation. DESIGN: A comprehensive 10-year
retrospective review of burn injuries from 1999. OUTCOME MEASURES: Age, sex,
date, mechanism of injury, location of incident, on scene vitals and GCS, type of
transport to hospital and routing, ISS, presenting vitals and GCS, diagnoses,
procedures, complications, hospital LOS, ICU LOS, and events surrounding the
injury. RESULTS: One hundred and seventy five patients (79.4% M, 20.6% F) were
identified as having traumatic burn injuries with a mean ISS score of 21.8 (+/
8.3). The mean age was 41.6 (+/-17.5) (range 14-94) years. Nearly half (49.7%) of
patients suffered their injuries at home, 17.7% were related to industrial
incidents and 14.3% were MVC related. One hundred and ten patients required ICU
admission. ICU LOS 18.5 (+/-8.8) days. Hospital LOS 38.0 (+/-37.8) days. The mean
extent of burn injury was 31.4 (+/-20.9) % TBSA. Nearly half of the patients
suffered inhalational injuries (mild 12.5%, moderate 13.7%, severe 9.1%). Thirty
nine (22.2%) of patients died from their injuries. Routine IAP monitoring began
in September, 2005 with 15 of 28 patients having at least two IAP measurements.
The mean IAP was 16.5 (+/-5.7) cm H2O (range: 1-40) with an average of 58 (+/-97)
IAP measurements per patient. Those patients with IAP monitoring had an average
TBSA of 35.0 (+/-16.0)%, ISS of 47.5 (+/-7.5). The mean 48 hr fluid balance was
25.6 (+/-11.1)L exceeding predicted Parkland formula estimates by 86 (+/-32)%.
CONCLUSIONS: Further evaluation of IAP monitoring is needed to further
characterize IAP and fluid resuscitation in patients with burn injuries.
PMID- 25132865
TI - Heat Stress Increases Long-term Human Migration in Rural Pakistan.
AB - Human migration attributable to climate events has recently received significant
attention from the academic and policy communities (1-2). Quantitative evidence
on the relationship between individual, permanent migration and natural disasters
is limited (3-9). A 21-year longitudinal survey conducted in rural Pakistan (1991
2012) provides a unique opportunity to understand the relationship between
weather and long-term migration. We link individual-level information from this
survey to satellite-derived measures of climate variability and control for
potential confounders using a multivariate approach. We find that flooding-a
climate shock associated with large relief efforts-has modest to insignificant
impacts on migration. Heat stress, however-which has attracted relatively little
relief-consistently increases the long-term migration of men, driven by a
negative effect on farm and non-farm income. Addressing weather-related
displacement will require policies that both enhance resilience to climate shocks
and lower barriers to welfare-enhancing population movements.
PMID- 25132866
TI - Treatment of Crohn's disease complicated with myelodysplastic syndrome via
allogeneic hematopoietic stem cell transplantation: case report and literature
review.
AB - Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal
tract arising in individuals with genetic predisposing factors and abnormalities
of the immune system. Myelodysplastic syndrome (MDS), an acquired clonal
hematologic disorder, is characterized by peripheral blood cytopenia, dysplastic
changes in several types of hematopoietic cells of the bone marrow and peripheral
blood, and a high risk of transformation to acute leukemia. CD rarely occurs in
combination with MDS, and MDS treatment with hematopoietic stem cell
transplantation (HSCT) has not been frequently reported. We report the case of a
50-year-old Chinese male who presented with abdominal pain, diarrhea, and
fatigue. CD was diagnosed by colonoscopy, imaging studies, and pathological
examination. He was initially treated with mesalazine and prednisone and
thereafter he presented with pancytopenia. MDS (RAEB-I) was diagnosed by bone
marrow examination, and karyotyping revealed 47, XY, +8. The patient was treated
with thalidomide, andriol, and decitabine. Allogeneic HSCT was performed with a
human leukocyte antigen-matched sibling as the donor. The patient is currently
well at 14 months after HSCT, without abdominal pain, diarrhea, or fatigue. HSCT
may be a promising treatment option for patients with combined CD and MDS.
PMID- 25132868
TI - Basic aspects of the pharmacodynamics of tolperisone, a widely applicable
centrally acting muscle relaxant.
AB - Tolperisone (2-methyl-1-(4-methylphenyl)-3-piperidin-1-ylpropan-1-one hydro
chloride) was introduced in the clinical practice more than forty years ago and
is still evaluated as a widely applicable compound in pathologically elevated
skeletal muscle tone (spasticity) and related pains of different origin. In the
present review, basic pharmacodynamic effects measured on whole animals, analyses
of its actions on cell and tissue preparations and molecular mechanism of action
on sodium and calcium channels are summarized as recently significantly new data
were reported.
PMID- 25132867
TI - Successful natural interferon-beta plus ribavirin therapy in a chronic hepatitis
C patient after discontinuation of interferon-alpha treatment due to arrhythmia
and interstitial pneumonia.
AB - A 71-year-old female patient with hepatitis C virus genotype 1 had previously
discontinued interferon (IFN)-alpha plus ribavirin therapy, pegylated IFN-alpha
(pegIFN-alpha) monotherapy, and natural IFN-alpha monotherapy because of
arrhythmia, interstitial pneumonia, and severe neurovegetative symptoms. She
subsequently completed 72 weeks of natural IFN-beta plus ribavirin therapy
without remarkable adverse effects and achieved a sustained viral response,
suggesting differences in the pharmacological properties and biological effects
of IFN-alpha and IFN-beta. Thus, natural IFN-beta plus ribavirin therapy may be a
treatment option for patients with poor tolerance to IFN-alpha or pegIFN-alpha
treatments.
PMID- 25132862
TI - Challenges associated with Penetration of Nanoparticles across Cell and Tissue
Barriers: A Review of Current Status and Future Prospects.
AB - Nanoparticles (NPs) have emerged as an effective modality for the treatment of
various diseases including cancer, cardiovascular and inflammatory diseases.
Various forms of NPs including liposomes, polymer particles, micelles,
dendrimers, quantum dots, gold NPs and carbon nanotubes have been synthesized and
tested for therapeutic applications. One of the greatest challenges that limit
the success of NPs is their ability to reach the therapeutic site at necessary
doses while minimizing accumulation at undesired sites. The biodistribution of
NPs is determined by body's biological barriers that manifest in several distinct
ways. For intravascular delivery of NPs, the barrier manifests in the form of:
(i) immune clearance in the liver and spleen, (ii) permeation across the
endothelium into target tissues, (iii) penetration through the tissue
interstitium, (iv) endocytosis in target cells, (v) diffusion through cytoplasm
and (vi) eventually entry into the nucleus, if required. Certain applications of
NPs also rely on delivery through alternate routes including skin and mucosal
membranes of the nose, lungs, intestine and vagina. In these cases, the diffusive
resistance of these tissues poses a significant barrier to delivery. This review
focuses on the current understanding of penetration of NPs through biological
barriers. Emphasis is placed on transport barriers and not immunological
barriers. The review also discusses design strategies for overcoming the barrier
properties.
PMID- 25132869
TI - Contribution of neuraminidase of influenza viruses to the sensitivity to sera
inhibitors and reassortment efficiency.
AB - Live attenuated influenza vaccine (LAIV) represent reassortant viruses with
hemagglutinin (HA) and neuraminidase (NA) gene segments inherited from
circulating wild-type (WT) parental influenza viruses recommended for inclusion
into seasonal vaccine formulation, and the 6 internal protein-encoding gene
segments from cold-adapted attenuated master donor viruses (genome composition
6:2). In this study, we describe the obstacles in developing LAIV strains while
taking into account the phenotypic peculiarities of WT viruses used for
reassortment. Genomic composition analysis of 849 seasonal LAIV reassortants
revealed that over 80% of reassortants based on inhibitor-resistant WT viruses
inherited WT NA, compared to 26% of LAIV reassortants based on inhibitor
sensitive WT viruses. In addition, the highest percentage of LAIV genotype
reassortants was achieved when WT parental viruses were resistant to non-specific
serum inhibitors. We demonstrate that NA may play a role in influenza virus
sensitivity to non-specific serum inhibitors. Replacing NA of inhibitor-sensitive
WT virus with the NA of inhibitor-resistant master donor virus significantly
decreased the sensitivity of the resulting reassortant virus to serum heat-stable
inhibitors.
PMID- 25132870
TI - Respiratory Syncytial Virus Infection in High-risk Infants - an Update on
Palivizumab Prophylaxis.
AB - Morbidity due to respiratory syncytial virus (RSV) disease is still high in
infants and children worldwide during the first two to five years of life.
Certain categories of high-risk infants with increased morbidity and mortality
attributed to RSV disease have been identified and are included in national
recommendations for prophylaxis with the monoclonal RSV antibody palivizumab.
Most guidelines recommend palivizumab for preterm infants born less than or equal
to 32 weeks gestational age with or without bronchopulmonary dysplasia, those
born between 33 and 35 weeks gestational age with additional risk factors, and
infants and children with hemodynamically significant congenital heart disease.
Over the last years several rare diseases have been identified demonstrating high
morbidity associated with RSV disease, thus, extension of guidelines for the
prophylaxis with palivizumab for these patients with rare diseases including
children with malignancy, congenital and acquired immune deficiency, Down
syndrome, neuromuscular impairment, cystic fibrosis, congenital diaphragmatic
hernia and other severe respiratory disease is increasingly discussed. Efficacy
of palivizumab prophylaxis is documented by meta-analysis, and different economic
analyses demonstrate cost-effectiveness of palivizumab for the most common
indications during the first RSV season.
PMID- 25132871
TI - Classification of distal radius physeal fractures not included in the salter
harris system.
AB - INTRODUCTION: The most commonly used classification for pediatric physeal
fractures has been proposed by Salter and Harris. Among the most suitable
classification schemes are those proposed by Ogden and Peterson who added several
new types of injuries. The purpose of this study was to examine the value of both
schemes to classify all different types of physeal injuries of the distal radius
that are not included in the Salter-Harris system and to test a new nomenclature
to classify and guide treatment for the whole spectrum of these injuries.
METHODS: A total of 292 children who were admitted for a physeal fracture of the
distal radius that could not be classified according to the Salter-Harris system
were identified from the hospital database. All radiographs were carefully
examined and classified according to the existing classifications of Ogden and
Peterson and a modified classification scheme. The results of the treatment were
also evaluated. RESULTS: Ninety-six physeal injuries could not be classified
using the classification schemes of Ogden and Peterson. All injuries could be
classified in five types using the new, modified nomenclature. Growth
abnormalities of the distal radius were evaluated after an average follow-up time
of 11 years. Growth arrest due to a physeal bar was detected only in one patient.
DISCUSSION: The proposed modified scheme is practical, incorporates all previous
classification systems, allows classification of all physeal injuries of the
distal radius that are not included in the Salter-Harris system and may assist
comparison of treatment outcomes.
PMID- 25132872
TI - Tranexamic Acid Reduces Blood Loss and Transfusion in Patients Undergoing Total
Knee Arthroplasty without Tourniquet: A Prospective Randomized Controlled Trial.
AB - INTRODUCTION: Blood loss during and after total knee arthroplasty (TKA) can lead
to substantial morbidity and the need for blood transfusions. There are several
methods to minimize blood loss and to decrease transfusion rates in patients
undergoing TKA. Tranexamic acid is an antifibrinolytic agent with known efficacy
for achieving these goals. Currently, many surgeons are performing TKA without
the use of tourniquet. Consequently, the aim of the study is to evaluate whether
tranexamic acid reduces blood loss during and after TKA without the adjunctive
use of above-the-knee tourniquet. METHODS: We performed a prospective randomized
controlled trial (1:1 fashion) on the use of tranexamic acid versus placebo in 50
patients undergoing TKA (without tourniquet). The treatment group received two
(preoperative and postoperative) 15 mg/kg doses. The primary endpoint was blood
transfusion rate. We collected data about demographic and procedural
characteristics, hemoglobin and hematocrit values, drain blood loss at 24 hours
as well as adverse events. RESULTS: There were no transfusions in the treatment
group, whereas 32% of the control group required transfusion (p<0.01). The
treatment group had higher hematocrit and hemoglobin levels at 24, 48 and 72
hours after surgery (all p<0.01) and lower drain loss at 24hours (363.4+/-141 vs
626+/-260ml, p=<0,001). There were no in-hospital or six-month thromboembolic
complications. DISCUSSION: A double-dose of tranexamic acid was safe and
effective, reducing blood loss and preventing the need of blood transfusion in
patients undergoing TKA without above-the-need tourniquet.
PMID- 25132873
TI - Social Variations in Perceived Parenting Styles among Norwegian Adolescents.
AB - Previous research has documented the associations between parenting and parenting
styles and child and adolescent outcomes. Little is known, however, about the
social structuring of parenting in contemporary Nordic welfare states. A possible
hypothesis is that socioeconomic variations in parenting styles in present-day
Norway will be small because of material affluence, limited income inequality,
and an active welfare state. This study examines social variations in parenting
as perceived by Norwegian adolescents (N = 1362), with a focus on four parenting
style dimensions: responsiveness, demandingness, neglecting, and intrusive.
Responsiveness seems to capture major divisions in parenting. Adolescents in
families with fewer economic resources experienced their parents as somewhat less
responsive, but responsiveness was not related to parents' education. Low
parental education was on the other hand associated with perceptions of parents
as neglecting and intrusive. Viewing parents as demanding did neither vary with
parental education nor with family economy. Substantial variations in parenting
styles persist in present-day Norway, and these variations correspond moderately
with the families' placement in the social structure. Indicators of parenting and
parenting styles may be useful indicators of some aspects of child and adolescent
well-being.
PMID- 25132874
TI - Medication adherence and community pharmacy: a review of education, policy and
research in England.
AB - OBJECTIVE: The objective of this narrative review was to identify and describe
the current policy, education and research related to community pharmacy and
medication adherence in England. METHODS: Medline, Embase, International
Pharmaceutical Abstracts and Pharmline were used to search for relevant research
articles. Current policy documents were identified via the websites of the
Department of Health in England, the Royal Pharmaceutical Society of Great
Britain, the National Pharmacy Association, the Pharmaceutical Services
Negotiating Committee and NHS Employers. All pharmacy schools in England were
contacted to obtain information about the adherence-related courses they provide
to undergraduate and postgraduate pharmacy students. RESULTS: National policies
and guidelines in England are conducive to an increasing role for community
pharmacists to support patients with medication adherence. Many pharmacy schools
cover the issue of adherence in their undergraduate and postgraduate courses.
Research in this area has tested the effectiveness of pharmacists providing
adherence support in the form of compliance aids, education, involvement in
discharge planning, and tailored interventions. CONCLUSION: In community pharmacy
in England, current policy and funding arrangements suggest there is great scope
for pharmacists to support patients with medication adherence. Further research
is necessary to identify the most useful, cost-effective and sustainable approach
in practice.
PMID- 25132875
TI - Pharmacists' perceptions of the impact of care they provide.
AB - Limitations on health care resources necessitate careful focus on activities that
lead to the greatest improvement in patient outcomes. Despite the importance of
aligning pharmacists' time with activities deriving the most impact, there is a
paucity of literature on the correlations between pharmacists' perceptions of the
impact of their activities, how they actually spend their time and how these
align with published evidence of impacts on patient outcomes. OBJECTIVE: To
reveal hospital pharmacists' perceptions of the impacts of their clinical
activities and to characterize the correlation between the activities performed
and both their perceptions of and the published evidence for their impacts on
patient care. METHODS: Observational qualitative interviews and quantitative
questionnaires were conducted with each participant (N=21) to characterize their
work day and determine their perceptions of the impact of their activities. A
systematic literature review catalogued pharmacists' activities with impact on
patient outcomes. Primary endpoint: degree of correlation in three pair-wise
comparisons between pharmacists' perceptions of impact, time allotted to
activities, and published evidence of impact. RESULTS: Pharmacists' time spent
was positively and significantly correlated with their perception of impact
(P=0.037) but not with the published evidence of impact (in either of the two
analytical scenarios). The correlation between published evidence and
pharmacists' perceptions of impacts was on the threshold of statistical
significance with a moderate strength of association in one of the two analytical
scenarios used. CONCLUSIONS: Pharmacists dedicate more of their clinical time to
activities they perceive to have greater impact. However, these perceptions and
their time allocation does not correlate well with published evidence, and some
misperceptions about impacts deserve correction. More rigorous research is needed
to quantify the value of pharmacist services to the health care system, however
designing such studies to isolate the value of specific activities will be
challenging.
PMID- 25132876
TI - Parent's knowledge and management of their children's ailments in Malaysia.
AB - Minor ailments like sore throat, fever, cough and diarrhea can be relieved with
over-the-counter (OTC) medications such as paracetamol or other traditional
remedies, without seeking for consultation from general practitioners. Parents
usually take the responsibility to come up with some kind of treatment for their
children. OBJECTIVE: (1) to evaluate the parents' medical knowledge about OTC
medicines which are usually used by the parents to treat their children and (2)
to evaluate the parents' management in dealing with their children's ailments,
and (3) to evaluate the association between medical knowledge and the management
of children's ailments related to medicine use among the parents. METHODS: A
cross-sectional survey was conducted to measure the parents' knowledge about
their children's ailments. Subjects were selected and information was obtained in
September 2008. Non-probability convenient sampling method was used. Parents were
recruited from the general public to answer the questionnaires. RESULTS: 197
parents filled in the questionnaires. From the total respondents, 48.2% of them
were male. This study showed that most respondents have medium knowledge (6.11
SD=3.6) and a moderate management (4.39 SD=2.7). The results showed that there is
a significant difference between the knowledge and the management level of
ailments (P=0.033). Regarding the education level of the parents and the
socioeconomic status, the p-value showed there was a significant difference
between parents' knowledge and their education level (P=0.012). CONCLUSION: This
study showed that parents have inadequate knowledge and some misconception about
how to go about treating their children when they are unwell. It is hoped that by
identifying weak areas in parents' management to their children's ailments,
better planned educational and behavioral modification efforts can be made to
elevate the knowledge level among the parents when they medically treat their
children.
PMID- 25132877
TI - The impact of an immunization training certificate program on the perceived
knowledge, skills and attitudes of pharmacy students toward pharmacy-based
immunizations.
AB - OBJECTIVE: To assess the impact of a national immunization training certificate
program on the perceived knowledge, skills and attitudes of pharmacy students
toward pharmacy-based immunizations. METHODS: The study design utilized a pre-
and post-survey administered to pharmacy students before and after the American
Pharmacists Association's (APhA) Pharmacy-Based Immunization Delivery program.
The primary outcome explored was a change in the perceived knowledge, skills, and
attitudes of the pharmacy students. A five-point Likert scale (i.e. strongly
agree = 5, strongly disagree = 1) was used for measuring the main outcomes, which
was summated by adding the individual item scores in each section to form a
composite score for each outcome. RESULTS: The certificate training program
resulted in a significant improvement in knowledge (38.5% increase in score,
p<0.001) and skills (34.5% increase in score, p<0.001), but not attitudes (1%
increase in score, p=0.210). CONCLUSIONS: The national immunization training
certificate program had a positive impact on the perceived knowledge and skills
of pharmacy students. However, no change was observed regarding students'
perceived attitudes toward pharmacy-based immunizations.
PMID- 25132879
TI - Willingness to pay for a pharmacist's dispensing service: a cross-sectional pilot
study in the state of Penang, Malaysia.
AB - OBJECTIVE: The aim of this pilot study was to assess the value of the dispensing
service of pharmacists from the general public's perspective using the contingent
valuation technique in the State of Penang, Malaysia. METHODS: Participants were
conveniently sampled from malls and were given a self-completed questionnaire
that collected the patient's demographic information and their knowledge about
the pharmacist's dispensing service. They were then presented with a description
of the pharmacist's dispensing service, the risk of medication errors in
prescriptions and their consequences, and the risk reduction of medication errors
associated with pharmacist intervention. The willingness to pay (WTP) of the
participants was later assessed using a contingent valuation interview that asked
the likelihood and maximum amount they were willing to pay. RESULTS: In the
study, 100 people participated, and 57% were aged between 18 and 35 years. Of
these participants, 51% were women, and 46% of them earned more than 1000 MYR
(285.71USD) per month. In addition, 8% of the participants had never visited a
community pharmacy. Finally, 67% of the participants were willing to pay for the
pharmacists' dispensing service, and the median amount that the participants were
willing to pay was 10 MYR (2.86USD). The WTP amount was moderately correlated
with their knowledge of the community pharmacist's dispensing services (r=0.377,
p=0.02). CONCLUSION: Generally, the public valued the pharmacist's dispensing
service. Their acceptance can be further improved by educating the public on the
role of the pharmacist.
PMID- 25132878
TI - Pharmacists' attitude, perceptions and knowledge towards the use of herbal
products in Abu Dhabi, United Arab Emirates.
AB - OBJECTIVE: The purpose of the study was to assess pharmacists' current practice,
perception and knowledge towards the use of herbal products in Abu Dhabi, United
Arab Emirates (UAE). The study assessed the need for incorporating herbal
medicine as a separate topic in under- graduate pharmacy student curricula.
METHODS: The study was done on 600 pharmacists employed in Abu Dhabi, who were
contacted electronically, out of which 271 had completed the survey. The data was
collected using a structured questionnaire. RESULTS: Pharmacists' use of herbal
products is high in the UAE, as they have a high belief on the effectiveness of
herbal products, and only age was found to be the most predominant variable that
was influencing pharmacists' personal use of herbal products (p-value=0.0171).
Pharmacists were more knowledgeable on the uses/indications of herbal products
(47%) rather than on other areas. Knowledge of the dispensing mode (prescription
only or over the counter medicines) mandated by the Ministry of Health was quite
good, however, it is to be noted that the source of information on the dispensing
mode was provided by medical representatives (48%). Knowledge of dispensing mode
of herbal products was found to be significantly influenced by the place of work
with more knowledge of the dispensing mode by pharmacists working in the private
sector (p-value 0.0007). The results from the study also underscores the need for
including herbal medicine as a separate topic in pharmacy college curriculum and
to provide for more seminars and continuing pharmacy education programs targeting
pharmacists in the Emirate of Abu Dhabi. CONCLUSIONS: Pharmacists need to be
informed on indications, drug interactions, adverse events and precautions of
herbal products. Concerned bodies must also provide them with regular continuing
education programs apart from putting their efforts to incorporate relevant
topics on herbal medicine in the pharmacy students' curriculum.
PMID- 25132880
TI - Barriers to medication counselling for people with mental health disorders: a six
country study.
AB - Provision of medication information may improve adherence and prevent medication
related problems. People with mental health disorders commonly receive less
medication counselling from pharmacists than people with other common long term
and persistent disorders. OBJECTIVE: The objective of this study was to compare
and contrast barriers pharmacy students perceive toward providing medication
counselling for people with mental health disorders in Australia, Belgium,
Estonia, Finland, India and Latvia. METHODS: Barriers identified by third-year
pharmacy students as part of the International Pharmacy Students' Health Survey
were content analysed using a directed approach. Students' responses were
categorised as pharmacist related, patient related, health-system related, or
social or cultural related. Quantitative data were analysed using SPSS version
14.0. RESULTS: Survey instruments were returned by 649 students. Of the
respondents, 480 identified one or more barriers to medication counselling for
people with mental health disorders. Patient related factors accounted for
between 25.3% and 36.2% of barriers identified by the pharmacy students.
Pharmacist related factors accounted for between 17.6% and 45.1% of the barriers
identified by the pharmacy students. Students in India were more likely to
attribute barriers to pharmacist and social and cultural related factors, and
less likely to health-system related factors, than students studying in other
countries. CONCLUSION: The nature of barriers identified by pharmacy students
differed according to the country in which they studied. Undergraduate and
postgraduate pharmacy education programs may need to be amended to address common
misconceptions among pharmacy students.
PMID- 25132881
TI - Comparison of prescribing criteria in hospitalised Australian elderly.
AB - The Beers criteria (2003) and McLeod criteria (1997) have been applied
internationally to quantify inappropriate prescribing in elderly populations.
Similarly, guidelines have been published locally by the National Prescribing
Service (NPS). OBJECTIVE: This study aimed to adapt, evaluate and compare the
utility of these three established criteria in measuring prescribing
appropriateness in a sample of hospitalised elderly patients. METHODS: Initial
refinement of the criteria produced versions applicable to Australian practice.
Inpatient records of 202 patients aged 65 years or older in six wards of the
Princess Alexandra Hospital, Brisbane, Australia, were reviewed using the adapted
criteria. 'Potentially inappropriate' prescribing was descriptively analysed
using relevant denominators. RESULTS: The adapted criteria collectively listed 70
'potentially inappropriate' medicines or drug groups and 116 'potentially
inappropriate' prescribing practices. Patients (mean age 80.0; SD=8.3 years) were
prescribed, a median of eight medicines (SD=4.0). At least one 'potentially
inappropriate' medicine was identified in 110 (55%) patients. 'Potentially
inappropriate' prescribing practices averaged 1.1 per patient (range 1-6). The
adapted Beers criteria identified more 'potentially inappropriate'
medicines/practices (44%, 101/232) than the McLeod criteria (41%) and NPS
criteria (16%). Aspirin, benzodiazepines, beta-blockers and dipyridamole were
most commonly identified. CONCLUSION: The Beers and McLeod criteria, developed
internationally, required considerable modification for local prescribing. The
three criteria differed in their focus and approaches, such that development and
validation of national criteria, using the key features of these models, is
recommended. There is potential to apply validated guidelines in clinical
practice and review of prescribing, but only to supplement clinical judgement.
PMID- 25132882
TI - Pharmacists' participation in the documentation of medication history in a
developing setting: An exploratory assessment with new criteria.
AB - OBJECTIVE: To assess the impact of pharmacists' participation on the frequency
and depth of medication history information documented in a developing setting
like Nigeria. METHOD: The study consisted of two phases. The first phase was a
baseline cross-sectional assessment of the frequency and depth of medication
history information documented by physicians in case notes of systematic samples
of 900 patients that were stratified over 9 Medical outpatients Units at a
premier teaching hospital in south western Nigeria. The second phase was an
exploratory study involving 10 pharmacists who conducted cross-sectional
medication history interview for 324 randomly selected patients. RESULTS: 49.2%
of patients, whose medication history were documented at the baseline, by
physicians, were males; while 50.3% of patient interviewed by pharmacists were
male. Mean age (SD) of males and females whose medication histories were
documented by physicians and pharmacists were 43.2 (SD=18.6), 43.1 (SD=17.9)
years and 51.5 (SD=17.6), 52.1 (SD=17.4) years respectively. The frequency of
medication history information documented by pharmacists was significantly higher
for twelve of the thirteen medication history components (P < 0.0001). These
include prescription medicines; over the counter medicines; source of medicines;
adverse drug reactions; allergy to drugs, allergy to foods, allergy to chemicals;
patient adherence; alcohol use; cigarette smoking; dietary restrictions and
herbal medicine use. The depth of medication history information acquired and
documented by pharmacist was significantly better for all the thirteen medication
history components (P<0.0001). CONCLUSION: Pharmacists' participation resulted in
significant increase in frequency and depth of medication history information
documented in a developing setting like Nigeria. The new medication history
evaluation criteria proved useful in assessing the impact of pharmacists'
participation.
PMID- 25132883
TI - Evaluating the impact of new anticoagulants in the hospital setting.
AB - The short-comings of current anticoagulants have led to the development of newer,
albeit more expensive, oral alternatives. OBJECTIVE: To explore the potential
impact the new anticoagulants dabigatran and rivaroxaban in the local hospital
setting, in terms of utilisation and subsequent costing. METHOD: A preliminary
costing analysis was performed based on a prospective 2-week clinical audit (29th
June - 13th July 2009). Data regarding current anticoagulation management were
extracted from the medical files of patients admitted to Ryde Hospital. To model
potential costing implications of using the newer agents, the reported incidence
of VTE/stroke and bleeding events were obtained from key clinical trials.
RESULTS: Data were collected for 67 patients treated with either warfarin (n=46)
or enoxaparin (n=21) for prophylaxis of VTE/stroke. At least two-thirds of all
patients were deemed suitable candidates for the use of newer oral anticoagulants
(by current therapy: warfarin: 65.2% (AF), 34.8% (VTE); enoxaparin: 100%, (VTE)).
The use of dabigatran in VTE/stroke prevention was found to be more cost-
effective than warfarin and enoxaparin due to significantly lower costs of
therapeutic monitoring and reduced administration costs. Rivaroxaban was more
cost-effective than warfarin and enoxaparin for VTE/stroke prevention when
supplier-rebates (33%) were factored into costing. CONCLUSION: This study
highlights the potential cost- effectiveness of newer anticoagulants, dabigatran
and rivaroxaban, compared to warfarin and enoxaparin. These agents may offer
economic advantages, as well as clinical benefits, in the hospital-based
management of anticoagulated patients.
PMID- 25132884
TI - Evaluation of pharmacy students' clinical interventions on a general medicine
practice experience.
AB - As colleges of pharmacy prepare a new generation of practitioners, it is
important that during practice experiences students learn the impact of clinical
interventions. For over ten years, pharmacy students have been a vital part of
the multidisciplinary team at the military treatment facility. The overall impact
of the student interventions on patient care has not been evaluated. To evaluate
the impact, the students began documenting their clinical interventions in
Medkeeper RxInterventionsTM, an online database. The program is used to document
faculty and fourth year pharmacy students' pharmaceutical interventions.
OBJECTIVE: The objective of this study was to analyze the interventions completed
by fourth year pharmacy students during a general medicine advanced pharmacy
practice experience at a military treatment facility. METHODS: The students
completing their general medicine advanced pharmacy practice experience at the
military treatment facility are responsible for self reporting all interventions
made during clinical rounds into the Medkeeper RxInterventionTM database. The
researchers retrospectively collected and analyzed interventions made from June
2008 to June 2009. RESULTS: The total number of interventions recorded by 8
fourth year pharmacy students was 114. Students averaged a number of 14.3
interventions during an eight week practice experience. Students spent an average
of 5 minutes per intervention. Ninety- five percent of the interventions were
accepted. CONCLUSION: Fourth year pharmacy students' recommendations were
accepted at a high rate by resident physicians. The high acceptance rate may have
the ability to positively impact patient care.
PMID- 25132885
TI - Defining bioidentical hormones for menopause-related symptoms.
AB - In the last decade, the use of bioidentical hormones (BHs) to treat menopause
related symptoms has become increasingly popular. However, the many different
definitions of BHs have led to a great deal of confusion often making it
difficult for health care providers to discuss this area with patients.
OBJECTIVE: The purpose of this paper was to produce a concise definition of
bioidentical hormones, based on a review of the literature. METHODS: Searches,
using systematic review methodology, were conducted from inception to June 2010
in PubMed, EMBASE, IPA, The Journal of International Compounding and the Internet
to identify definitions of bioidentical hormones. There were no restrictions on
type, date or language of publication. Included papers/website included those
that contained a definition of BHs. Definitions were extracted, similarities and
differences summarized, and these were then examined to produce a concise
definition. RESULTS: Sixty-three definitions were found. Based on the analysis of
similarities and differences, the following definition, comprised of three
components (term being defined; category to which term belongs; distinctive
characteristics of term) was produced: "Bioidentical hormones are chemical
substances that are identical in molecular structure to human hormones."
CONCLUSIONS: This definition clearly and concisely explains the meaning of BHs
which should lead to a common understanding of the term and limit confusion among
health care providers, the general public and the scientific community.
PMID- 25132886
TI - Comparison of prescribing and dispensing processes between veterinarians and
pharmacists in New Zealand: Are there opportunities for cooperation?
AB - BACKGROUND: Prescribing and dispensing of medicines are fundamental processes in
providing healthcare for both human and animal patients. There has been recent
discussion in the literature to advocate for increased co-operation between
pharmacists and veterinarians, however there is little data available about
veterinary prescribing and dispensing processes. OBJECTIVE: The aims of this
study were to gain information on veterinary prescribing and dispensing processes
for companion animals in the Dunedin region of New Zealand. METHODS: Open
interviews were conducted with a selection of five veterinarians at practices in
Dunedin. All interviews were transcribed verbatim. RESULTS: In New Zealand almost
all dispensing of medicines for animals is carried out by veterinarians or their
staff. There is a lack of standard treatment guidelines and a lack of regulation
around the treatment period for which medicines can be dispensed at one time
(i.e. period of supply). Medicines for animals are sometimes dispensed by
community pharmacies, where clients are experiencing financial difficulties or
when particular medicines are not held by veterinary practices. Record keeping
requirements and practices for veterinarians are similar to those for community
pharmacies. CONCLUSIONS: Processes undertaken by veterinarians in terms of
prescribing and dispensing were similar to pharmacists' practices for human
patients and so there is opportunity for collaboration between the two
professions. Pharmacists also have complementary knowledge about dosing and
formulating medicines that can assist in delivering optimal healthcare to animal
patients.
PMID- 25132887
TI - Hyperlipidemia medication management in patients admitted for a myocardial
infarction.
AB - OBJECTIVES: The purpose of this study is to determine the percentage of patients
admitted for acute myocardial infarction currently prescribed a statin, with low
density lipoprotein (LDL) <100 mg/dL, and high-density lipoprotein (HDL) <50
mg/dL for men and <55 mg/dL for women and evaluate their medication management
with a focus on niacin initiation. METHODS: This was a retrospective study from
12/07 to 12/09, conducted at a private, community hospital. Inclusion criteria
required patients to have an acute myocaridal infarction (AMI) ICD-9 code,
troponin >=0.2 ng/dL and lipid panel performed within 96 hours of troponin.
Patients with a triglyceride level > 400 mg/dL were excluded. The residual risk
population consisted of patients currently taking a statin with LDL <100 mg/dL
and HDL <50/55 mg/dL. Patients were excluded from the residual risk population if
they were on niacin, had an allergy to or previously failed niacin therapy, or
expired within 72 hours. RESULTS: A total of 553 patients experiencing an AMI had
lipid panels available for evaluation. The mean LDL was 97.3 +/- 36.0 mg/dL, mean
HDL was 33.5 +/- 11.1 mg/dL, and mean triglycerides were 133.1 +/- 71.3 mg/dL.
The majority of patients (n=521, 94.2%) had an HDL < 50 or 55 mg/dL respective of
gender. Ninety-two (80.0%) residual risk patients had no change in their home
lipid medications post AMI. Fifteen (13.0%) residual risk patients had their dose
of statin medication increased. Seven (6.1%) residual risk patients were
initiated on niacin. CONCLUSIONS: The study results confirm an existence of a
residual risk population with nearly 25% of AMI patients meeting the criteria.
The results also confirm a low incidence of medication intervention in the
residual risk population post AMI (20.0%) regarding lipid therapy, including the
initiation of niacin in only 6.1% of patients.
PMID- 25132889
TI - Unlocking the condoms: The effect on sales and theft.
AB - Community pharmacies may place condoms in locked displays or behind glass,
thereby reducing access and consequent use. OBJECTIVE: Quantify sales and theft
of condoms when condoms were unlocked and removed from behind glass in grocery
pharmacies. METHODS: Design. In this pilot study, condom displays were unlocked
in selected pharmacies for three months. Participants. Eight grocery pharmacies
in central Iowa agreed to participate. Intervention. Stores provided inventory at
baseline, sales/theft thereafter in three monthly reports and sales for the same
period one-year earlier. Outcome measures. Descriptive statistics quantified
condom theft and sales. Number of pharmacies leaving condoms unlocked after the
intervention was determined. RESULTS: Theft varied by pharmacy and ranged from an
average of 1.33 boxes (units) per month to 27.33 per month. All stores
experienced some increase in sales during the intervention. Two locations decided
to re-lock their displays, only one indicated theft as the reason. CONCLUSION:
After removing condoms from locked displays, more condoms were purchased and
stolen from the study pharmacies. Sales outweighed theft in all pharmacies.
PMID- 25132888
TI - Evaluation of the community pharmacist's behavior towards a prescription of
antidiabetic and antiasthma drugs.
AB - OBJECTIVE: The objective of this study is to assess the performance of community
pharmacist towards antidiabetic and antiasthma prescriptions, and also to assess
the lack of information provided by community pharmacists regarding patient
counseling and missing data, using a simulated patient technique. METHODS: A
prescription including antidiabetic and antiasthma drugs was used by simulated
patient to assess community pharmacist's performance in 194 pharmacies. A
performance assessment sheet was used to measure the patient counseling process.
A quantitative descriptive and comparative analysis was done for the collected
data. Pearson chi-square test (crosstabs) was used with a level of significance
95%). RESULTS: The analysis of the 194 pharmacies visited revealed that most of
the pharmacists were male (61%), Arabs (35%) and Indians (55%) with some other
nationalities. The dispensing time in the pharmacy ranged between 2 to 10
minutes. Spending time with patients was not affected by gender (p-value 0.087),
slightly affected by nationality (p-value 0.04), and highly affected by age (p
value 0.002) leaning towards older pharmacists who spent more time with patients
than younger pharmacists. Most pharmacists (90%) started preparing the
prescription once they received the prescription with no actual prescription
screening. fifty five percent of the pharmacists asked about the duration of the
treatment after preparing the prescription. ninety six percent did not counsel
patients about diet, exercise and lifestyle changes. Less than 40% asked if the
prescription was intended to be used for the same patient. CONCLUSION: This study
recommends that health authorities consider follow up plans in order to ensure
the best pharmaceutical care is provided by community pharmacies.
PMID- 25132890
TI - RETRACTED by plagiarism: Highly active antiretroviral therapy induced adverse
drug reactions in Indian human immunodeficiency virus positive patients.
AB - OBJECTIVE: To assess the incidence, severity pattern, causality, predictability
and preventability of adverse drug reactions (ADRs) and to identify risk factors
for adverse drug reactions in highly active antiretroviral therapy. METHODS:
Enrolled patients were intensively monitored for ADRs to highly active
antiretroviral therapy. Predictability was assessed based on history of previous
exposure to the drug or literature incidence of ADRs. Preventability was assessed
using Schumock and Thornton criteria and severity was assessed using modified
Hartwig and Siegel scale. Multivariate logistic regressions were used to identify
the risk factors for ADRs. RESULTS: Monitoring of 130 retropositive patients by
active pharmacovigilance identified 74 ADRs from 57 patients. Anemia and
hepatotoxicity were the most commonly observed ADRs. The organ system commonly
affected by ADR was red blood cell (21.4%). The ADRs were moderate in 77% of
cases. Type A reactions (77%) were more common. A total of 10.8% ADRs were
definitely preventable. The incidence rate of ADRs (65.9%) was highest with
Zidovudine + Lamivudine + Nevirapine combination. A total of 84% interruptions to
highly active antiretroviral therapy were due to toxicity. CD4 less than 200
cells/MUl, female gender and tuberculosis were observed as risk factors for ADRs.
CONCLUSION: Incidence of ADRs in intensively monitored patients was found to be
43.8%. Anemia in HIV patients is an influential risk factor for occurrence of
ADRs. With the increasing access to antiretroviral in India, clinicians must
focus on early detection and prevention of ADRs to highly active antiretroviral
therapy.
PMID- 25132891
TI - Comparison of robotic and open partial nephrectomy: Single-surgeon matched cohort
study.
AB - INTRODUCTION: We present comparative outcomes among matched patients who
underwent robotic partial nephrectomy (RPN) or open partial nephrectomy (OPN) by
a single surgeon at a single institution. METHODS: We reviewed the medical
records of 200 patients who underwent RPN (n = 100) or OPN (n = 100) between May
2003 and May 2013. The patients who underwent RPN were matched for age, gender,
body mass index (BMI), American Society of Anesthesiologists (ASA) score, as well
as tumour size, side and location. Perioperative outcomes were compared. RESULTS:
There was no significant difference between the 2 cohorts with respect to patient
age, BMI, ASA score, preoperative glomerular filtration rate, tumour size and the
R.E.N.A.L. nephrometry score. The mean operative time was longer in the RPN
group, but there were no significant differences with respect to warm ischemic
time and postoperative renal function. The length of hospitalization and use of
postoperative analgesics (ketoprofen) were more favourable in the RPN cohort.
There was no significant difference in the mean estimated blood loss, transfusion
rate, or complications between the cohorts. CONCLUSIONS: Considering the
perioperative and postoperative parameters, RPN is a viable option as a nephron
sparing surgical procedure for small renal masses that yields outcomes comparable
to those achieved with OPN. Despite matched cohort analysis among patients who
underwent PN by a single surgeon, there may be inherent selection bias; therefore
future prospective trials are needed.
PMID- 25132893
TI - High-grade microscopic hematuria in adult men can predict urothelial malignancy.
AB - INTRODUCTION: Microscopic hematuria in men younger than 40 is a confusing issue
to urologists, especially when these men have normal radiological findings. We
report our experience in looking for urologic malignancy in this group of
patients. METHODS: We conducted a prospective study for men with vague urological
symptoms. We included men under 40 years old, men with microscopic hematuria
greater than 25 red blood cells/high power field in 2 properly collected mid
stream urine samples, and men with free urine culture and normal multiphasic
computed tomography abdomen and pelvis studies. All patients underwent diagnostic
cystoscurethroscopy. If there were no lesions, multiple random biopsies were
taken. In cases of apparently normal cystoscopic findings and associated renal
colic, uretroscopy was done to the suspected side. RESULTS: Only 20 patients
fulfilled our inclusion criteria. The mean age of the patients were 34; 2
patients presented with pain. The other 18 patients were presenting with mild
recurrent lower urinary tract symptoms. Cystoscopy showed small papillary low
grade tumour in 3 patients. All random biopsies were free of malignancy.
Unilateral uretroscopy for the 2 cases presented with pain detected carcinoma in
situ in one of them. CONCLUSION: Cystoscopy is highly recommended for young adult
men, with significant levels of microscopic hematuria, due to the 20% incidence
rate of associated urological malignancy. Random bladder biopsies, in the absence
of suspicious lesions, have no diagnostic role, and should not be done.
Uretroscopy is advised for patients with microscopic hematuria and loin pain,
even in the absence of suspicious radiological findings.
PMID- 25132894
TI - A clinical study comparing BIVAP saline vaporization of the prostate with bipolar
TURP in patients with prostate volume 30 to 80 mL: Early complications,
physiological changes and postoperative follow-up outcomes.
AB - INTRODUCTION: We compare BIVAP saline vaporization of the prostate with bipolar
transurethral resection of the prostate (TURP) in the treatment of benign
prostatic hyperplasia. METHODS: In total, we included 86 patients treated with
BIVAP (n = 44) and bipolar TURP (n = 42). The inclusion criteria were maximum
urinary flow rate (Qmax) <=10 mL/s, International Prostate Symptom Score (IPSS)
>=16, and prostate volume measured with transrectal ultrasound scan between 30
and 80 mL. Serum electrolyte, hemoglobin, and hematocrit levels were determined
preoperatively and postoperatively. All patients were evaluated at the
postoperative first and third months and the IPSS score, post-void residual
urinary volume (PVR), Qmax, and average urinary flow rate (Qave) were compared.
Statistical analyses were performed using SPSS 16.0 program and statistical
significance was set at p < 0.05. RESULTS: Preoperative demographic
characteristics were similar in the 2 groups. The mean operation time was
significantly higher (p = 0.02) and hospitalization time was significantly lower
(p = 0.04) in the BIVAP group when compared to the bipolar TURP group. There was
no significant difference between 2 groups in terms of preoperative and
postoperative serum electrolyte, hemoglobin and hematocrit levels. Postoperative
complication rates were similar in the 2 groups. The only exception was the rate
of severe dysuria, which was significantly higher in the BIVAP group. No
statistical difference was noted between the groups in terms of postoperative
follow-up results. CONCLUSION: Bipolar TURP is a safe and highly effective
technique which can be used in the surgical treatment of benign prostatic
obstruction with minimal side effects. BIVAP saline vaporization of the prostate
seems to be a potential alternative to bipolar TURP with shorter hospitalization
time.
PMID- 25132892
TI - Predicting the Gleason sum of a patient with a prostate biopsy core Gleason <=7
and a prostate biopsy core Gleason >=8.
AB - INTRODUCTION: We review a subset of men who had discordant prostate biopsy sums
and were treated with radical prostatectomy. METHODS: Consecutive patients
treated with radical prostatectomy at The Ottawa Hospital between 2000 and 2012
were reviewed. Those with at least 1 prostate biopsy core of Gleason sum >=8 and
at least 1 prostate biopsy core of Gleason sum <=7 cancer were included. RESULTS:
Of the 764 radical prostatectomies, 661 (87%) were eligible for the study and 35
(5%) met inclusion criteria. Of these, only 16 (46%) had prostatectomy Gleason
sum of >=8. When the highest biopsy core was Gleason sum 8 (n = 24), only 7 (29%)
had a prostatectomy Gleason sum >=8. When the highest biopsy core was Gleason 9
(n = 11), 9 (82%) had a prostatectomy Gleason sum >=8 (relative risk [RR] 2.8; p
= 0.004). Patients with clinical T3 tumours were at higher risk of Gleason sum
>=8 compared to cT1 patients (RR 3.7; p = 0.008). Patient age (p = 0.89),
preoperative prostate-specific antigen (p = 0.34), prostate volume (p = 0.86),
number of biopsy cores (p = 0.18), and proportion of biopsy cores with cancer (p
= 0.96) were not strongly associated with risk of prostatectomy Gleason sum >=8.
CONCLUSION: These data should be considered when assigning patients into
prognostic risk categories based on prostate biopsy information. Further study to
verify our findings using larger samples is warranted.
PMID- 25132895
TI - [Not Available].
PMID- 25132896
TI - Retention of robot-assisted surgical skills in urological surgeons acquired using
Mimic dV-Trainer.
AB - INTRODUCTION: We assess the retention of robot-assisted surgical skills among
urologic surgeons. METHODS: The robot-assisted surgery skills of 20 urologic
surgeons were assessed using a Mimic dV-Trainer program (Mimic Technologies,
Inc., Seattle, WA) consisting of 6 tasks. These 20 surgeons had no previous
experience either using the Mimic dV-Trainer or acting as the main surgeon in
robot-assisted surgery. The surgeons completed the program 4 times in a row;
after 1 year, they completed it again for a fifth time. Performance scores were
recorded using the Mimic dV-Trainer's built-in algorithm. RESULTS: For all 6
tasks, there were significant improvements to the scores in the fourth trials
compared with those in the first trials. The scores in the fifth trials did not
significantly decline compared with those in the fourth trials. There was no
significant difference between the fifth trial scores of surgeons with
laparoscopic surgery skills/experience and those without. CONCLUSION: Our results
indicate that fundamental robot-assisted surgical skills can be retained in the
long-term after they are acquired.
PMID- 25132897
TI - Emphysematous cystitis and necrotizing fasciitis.
AB - Emphysematous cystitis is an uncommon and often severe infectious condition of
the bladder that usually affects women and diabetics. We report a case of a 62
year-old male patient who presented with concomitant emphysematous cystitis and
necrotizing fasciitis of the right leg. The patient was initially managed with
emergent disarticulation of the right leg. Tissue cultures were positive for
Ciprofloxacin-resistant Klebsiella pneumoniae. He was treated with Piperacillin
Tazobactam; however, due to the failure of conservative management of the
condition, the patient underwent a cystoprostatectomy with ileal conduit. To our
knowledge, this is the first report of concomitant emphysematous cystitis and
necrotizing fasciitis requiring aggressive surgical intervention for both
diseases.
PMID- 25132898
TI - A surgical challenge: Idiopathic scrotal elephantiasis.
AB - Scrotal elephantiasis is a condition rarely encountered in developed nations. It
is endemic in tropical regions due to the presence of filariasis (Wucheria
bancrofti). We report 2 cases of idiopathic scrotal elephantiasis in Canadian
citizens with no history of travel to endemic filariasis regions, malignancy,
surgery or radiation. Both patients underwent complete excision of the involved
tissue with reconstruction. We found that for advanced cases of scrotal
lymphedema, surgery is currently the only solution. In our cases of advanced
idiopathic disease, surgical treatment combining the expertise of a plastic
surgeon and a urologist provided a successful functional and cosmetic result.
PMID- 25132899
TI - Standardized follow-up program may reduce emergency room and urgent care visits
for patients undergoing radical prostatectomy.
AB - INTRODUCTION: The objective of the current study was to determine the impact of a
standardized follow-up program on the morbidity and rates of hospital visits
following radical prostatectomy (RP) in a tertiary, non-teaching urologic centre.
METHODS: Patients who underwent a RP in 2008 were retrospectively evaluated in
this study. Postoperative morbidity for the entire cohort was assessed using the
Modified Clavien Scale (MCS). Those patients readmitted to hospital or who
visited an urban or rural emergency department (ED) within 90 days of surgery
were further evaluated to determine the reason for readmission. RESULTS: At our
centre, 321 patients underwent RP in 2008 by 11 surgeons. Of the 321 patients, 77
(24.0%) visited an ED within 90 days, and 14 were readmitted to hospital, with an
additional patient readmitted directly (with a total 15 readmissions, 4.7%
overall). No patients died within the study period. In 2009 we launched a pilot
study wherein 115 RP patients received scheduled and on-demand follow-up care by
a dedicated nurse between May and November. We found that 90-day readmission
rates among this cohort dropped to 5% and 2.6% for ED visits and hospital
readmission, respectively. CONCLUSIONS: At our tertiary non-teaching centre, a
significant number of patients presented back to hospital within 90 days
following RP. Most of these patients (80.8%) were managed entirely through an
outpatient ED, and many visits were for routine postoperative care. Only 18.2%
(4.7% of the 321 prostatectomy patients) were readmitted to hospital. These data
point to a need for enhanced postoperative support of patients to reduce costly
and often unnecessary visits to acute care EDs. This conclusion is supported by
our early experience. Limitations include retrospective design, and variability
in practice of surgeons in this study.
PMID- 25132900
TI - Squamous cell carcinoma of the suprapubic tract: A rare presentation in patients
with chronic indwelling urinary catheters.
AB - Squamous cell carcinoma (SCC) of the bladder is uncommon, but can arise in the
setting of long-term bladder catheterization and chronic inflammation. SCC can
arise primarily from the suprapubic catheter tract, but fewer than 10 such cases
have been reported. We document 2 cases of SCC arising from the suprapubic tract
associated with chronic indwelling urinary catheters. SCC must be differentiated
from granulomatous conditions, which are quite common in patients with suprapubic
catheters.
PMID- 25132901
TI - Entertainment Venue Visiting and Commercial Sex in China.
AB - Entertainment venues in China play an important role in the sexually transmitted
disease (STD)/HIV epidemic. Most previous studies have focused on sex workers
working in entertainment venues, but little is known about their clients. This
study investigated the perceptions and behavior of the patrons visiting
entertainment venues. Qualitative in-depth interviews were conducted with 30 male
market vendors who visited entertainment venues at least once in the past 3
months in an eastern city in China. Information about their risky behavior,
attitude toward commercial sex, and STD/HIV prevention approaches was collected.
Saunas, karaoke bars, and massage centers are the most frequently visited
entertainment venues. Seventy-three percent of study participants reported
purchasing commercial sex at these entertainment venues. Participants expressed a
very liberal attitude toward commercial sex. Seeking commercial sex was perceived
as a characteristic of a male's nature. The perceived risks of STD/HIV infection
do not deter participants from engaging in commercial sex. Commercial sex clients
reported irregular condom use and a number of other misperceptions and improper
practices toward preventing STD/HIV infection. Venue-based intervention is
urgently needed to target the population. The sex workers themselves could
potentially serve as "health educators" to communicate prevention information to
their clients and encourage safer sex behavior.
PMID- 25132902
TI - Aortic arch calcification, procedural times, and outcomes of endovascular
treatment in patients with acute ischemic stroke.
AB - OBJECTIVE: To determine the frequency of aortic arch calcification and it's
relationship with procedural times, angiographic recanalization, and discharge
outcomes in acute ischemic stroke patients undergoing endovascular treatment.
METHODS: The thoracic component of computed tomographic (CT) angiogram were
reviewed by an independent reviewer to determine presence of any calcification;
and the severity of calcification was graded as follows: mild, single small
calcifications; moderate, multiple small calcifications; or severe, one or more
large calcifications. RESULTS: Aortic arch calcification was present in 120
(62.4%) of 188 patients and severity was graded as mild (n=24), moderate (n=44),
and severe (n=52). Compared with patients without calcification, the mean
intracranial access time (minutes +/- SD) was similar among patients with aortic
arch calcification (70 +/- 31 versus 64 +/- 31, p=0.9). The mean time
intracranial access time increased with increasing severity of aortic arch
calcification (61+/-27, 67+/-29, and 74+/-34, p=0.3). Patients with aortic arch
calcification had similar rates of complete or partial recanalization [85 (71%)
versus 50 (76%)], p=0.6) but lower rates of favorable outcomes [modified Rankin
scale 0-2] at discharge 27 (22%) versus 26 (39%), p=0.02). CONCLUSIONS: A high
proportion of acute ischemic stroke patients have aortic arch calcification which
is associated with lower rates of favorable outcome following endovascular
treatment. ABBREVIATIONS: SDstandard deviationICHintracerebral
hemorrhageNIHSSNational Institutes of Health Stroke ScaleTIAtransient ischemic
attackICHintracerebral hemorrhagemRSmodified Rankin scale.
PMID- 25132903
TI - Case report: Intra-procedural aneurysm rupture during endovascular treatment
causing immediate, transient angiographic vasospasm.
AB - INTRODUCTION: Cerebral vasospasm is a major cause of delayed ischemic cerebral
injury, typically occurring 3-14 days after subarachnoid hemorrhage (SAH). Ultra
early vasospasm is defined as angiographic vasospasm observed within 48 h of SAH
onset. Immediate vasospasm at the time of aneurysmal rupture has been suspected,
but has not been previously reported. We describe a case of immediate, transient
vasospasm following intra-procedural aneurysmal rupture. METHODS: A 55-year-old
woman presented with SAH from a ruptured anterior communicating artery aneurysm.
Subsequent coil embolization was complicated by an intra-procedural rupture
following placement of the initial coil. A follow-up angiogram obtained after 9
min demonstrated moderate-to-severe vasospasm in the A2 segments of both anterior
cerebral arteries. RESULTS: A repeat angiogram 20 min later demonstrated complete
resolution of the vasospasm. The aneurysm was successfully obliterated with coil
embolization. Post-procedure, the patient manifested no clinical vasospasm and
made a good neurological recovery. CONCLUSION: We document a case of ultra-early
cerebral vasospasm that occurred immediately after an intra-procedural aneurysmal
rupture. Catheter-induced vasospasm from mechanical manipulation of extracranial
vasculature is well described. However, immediate vasospasm related to
extravascular blood has never before been reported. This finding suggests that
extravascular blood can have a local direct effect (presumably mechanical) on
cerebral blood vessels, and may be an important mechanism for vasospasm.
PMID- 25132904
TI - Endovascular treatment of intracranial aneurysms by interventional neurologists:
first year single-center experience.
AB - BACKGROUND: Endovascular embolization of ruptured intracranial aneurysms provides
an adequate treatment and long-term results with less morbidity and mortality
(M&M) compared with surgical treatment. Since the last decade more and more
ruptured and unruptured intracranial aneurysms (IA) undergo endovascular
embolization in the United States. We present our experience of the initial one
year periprocedural M&M at Paul L. Foster School of Medicine (PLFSM), Texas Tech
Health Science Center (TTUHSC) in El Paso, Texas. METHODS: Demographics,
technical aspects of the endovascular procedure and clinical assessment,
including several commonly used scales to assess the severity in case of
subarachnoid hemorrhage were collected. Perioperative complications were
classified as minor and major. All data is prospectively collected in a local
database. Only endovascular treated aneurysms were included in the study.
RESULTS: During the first year of opening of the interventional neurology program
at our school of medicine (March 2011 and March 2012), a total 45 ruptured and
unruptured intracranial aneurysms were treated with endovascular embolization.
Two thirds of the patients (n = 27) presented with a ruptured IA. Within those
with a ruptured aneurysm, the most median Hunt and Hess grade was 3. By large the
vast majority of treated IA were in the anterior circulation and more than half
measured 7-12 mm. Only three unruptured IA were <7 mm (average 5.5 mm).
Complications occurred in seven patients (15%), four of them were minor without
any clinical sequelae. The remaining three included; intracranial dissection and
aneurysmal rupture resulting in both hemorrhagic or ischemic stroke and death in
only one patient. CONCLUSION: The first year experience of interventional
neurology services at Paul L. Foster School of Medicine in El Paso, Texas
demonstrates successful treatments with comparable national rates of morbidity
and mortality. ABBREVIATIONS: ACAAnterior cerebral arteryAcommAnterior
communicating arteryESNEndovascular surgical neuroradiologyH&HHunt and Hess
scaleIAIntracranial aneurysmICAInternal carotid arteryMCAMiddle cerebral
arteryM&MMorbidity and mortalitySAHSubarachnoid hemorrhagePcommPosterior
communicating arteryPLFSMPaul L. Foster School of MedicineTTUHSCTexas Tech
University Health Science CenterVAVertebral artery.
PMID- 25132905
TI - Reversible cerebral vasoconstriction syndrome and nonaneurysmal subarachnoid
hemorrhage.
AB - BACKGROUND: Reversible cerebral vasoconstriction syndrome was first described by
Call, Fleming, and colleagues. Clinically this entity presents acutely, with
severe waxing and waning headaches ("thunderclap"), and occasional fluctuating
neurological signs. CASE PRESENTATION: We present four subsequent cases of
patients with severe thunderclap headache and brain tomography with evidence of
subarachnoid hemorrhage. The brain angiogram showed no aneurysm but intracranial
vasculopathy consistent with multiple areas of stenosis and dilatation
(angiographic beading) in different territories. CONCLUSION: Neurologists should
be aware of Call Fleming syndrome presenting with severe headache and associated
convexity subarachnoid hemorrhage. After other diagnoses are excluded, patients
can be reassured about favorable prognosis with symptomatic management.
ABBREVIATIONS: RCVSReversible cerebral vasoconstriction syndromeCTComputed
tomographySAHSubarachnoid hemorrhageMRMagnetic resonanceCTAComputed tomography
angiographyMRAMagnetic resonance angiography.
PMID- 25132906
TI - Pattern of informed consent acquisition in patients undergoing emergent
endovascular treatment for acute ischemic stroke.
AB - BACKGROUND: Telephone consent and two physician consents based on medical
necessity are alternate strategies for time sensitive medical decisions but are
not uniformly accepted for clinical practice or recruitment into clinical trials.
We determined the rate of and associated outcomes with alternate consenting
strategies in consecutive acute ischemic stroke patients receiving emergent
endovascular treatment. METHODS: We divided patients into those treated based on
in-person consent and those based on alternate strategies. We identified clinical
and procedural differences and differences in hospital outcomes: symptomatic ICH
and favorable outcome (defined by modified Rankin Scale of 0-2 at discharge)
based on consenting methodology. RESULTS: Of a total of 159 patients treated, 119
were treated based on in-person consent (by the patient in 27 and legally
authorized representative in 92 procedures). Another 40 patients were treated
using alternate strategies (20 telephone consents and 20 two physician consents
based on medical necessity). There was no difference in the mean ages and
proportion of men among the two groups based on consenting methodology. There was
a significantly greater time interval incurred between CT scan and initiation of
endovascular procedure in those in whom in-person consent was obtained (117 +/-
65 min versus 101 +/- 45 min, p = 0.01). There was no significant difference in
rates of ICH (9% versus 8%, p = 0.9), or favorable outcome at discharge (28%
versus 30%, p = 0.8). CONCLUSIONS: Consent through alternate strategies does not
adversely affect procedural characteristics or outcome of patients and may be
more time efficient than in-person consenting process.
PMID- 25132907
TI - Right anterior choroidal artery syndrome: revisited.
PMID- 25132908
TI - Ulcerative colitis presenting with bilateral thalamic infarcts due to cerebral
sinus thrombosis.
PMID- 25132909
TI - Prevalence of vertebral artery origin stenosis and occlusion in outpatient
extracranial ultrasonography.
AB - BACKGROUND AND PURPOSE: Vertebral artery origin stenosis prevalence. Most data on
the prevalence of vertebral artery origin (VAo) disease is derived from hospital
based studies of patients with posterior circulation strokes and TIA. The
prevalence of VAo disease in patients without posterior circulation symptoms or
asymptomatic patients is poorly characterized. Our objective was to examine the
prevalence of VAo stenosis and occlusion in consecutive patients, presenting for
extracranial ultrasonography at an outpatient laboratory. METHODS: We
retrospectively identified 2490 consecutive extracranial duplex studies performed
in an ambulatory neurovascular ultrasound laboratory. All studies were reviewed
for the presence of >50% VAo stenosis, defined as a PSV > 114 cm/s, and VA
occlusion. We also reviewed the prevalence of >50% carotid stenosis, defined as a
PSV > 120 cm/s, in the same population, to draw comparisons with VAo stenosis
prevalence. RESULTS: We identified right VAo stenosis in 52/1955 (2.7%) and
occlusion in 74/ 1955 (3.9%) and left-sided VAo stenosis in 45/1973 (2.5%) and
occlusion in 64/1973 (3.6%). The prevalence of having any (either right or left)
VAo stenosis or occlusion was 8.2% and 1.4% had bilateral VAo stenosis or
occlusion. Right carotid stenosis and occlusion was found in 236/2399 (9.8%) and
53/2399 (2.2%), and left carotid stenosis and occlusion in 236/2397 (9.8%) and
45/2397 (1.9%), respectively. Any carotid disease, either right or left, was
present in 18.9% and 4.7% had bilateral carotid disease. CONCLUSION: Although
less prevalent than cervical carotid disease, we found that approximately 8% of
patients who reported to an ambulatory ultrasound laboratory had >50% VAo
disease.
PMID- 25132910
TI - Interpretation and Implementation of Intensive Blood Pressure Reduction in Acute
Cerebral Hemorrhage Trial (INTERACT II).
PMID- 25132911
TI - Subclinical Myocardial Disease in Heart Failure Detected by CMR.
AB - Noninvasive cardiac imaging plays a central role in the assessment of patients
with heart failure at all stages of disease. Moreover, this role can be even more
important for individuals with asymptomatic cardiac functional or structural
abnormalities-subclinical myocardial disease - because they could have benefits
from early interventions before the onset of clinical heart failure. In this
sense, cardiac magnetic resonance offers not only precise global cardiac function
and cardiac structure, but also more detailed regional function and tissue
characterization by recent developing methods. In this section, some of the main
methods available for subclinical myocardial disease detection are reviewed in
terms of what they can provide and how they can improve heart failure assessment.
PMID- 25132914
TI - Linking the Ohio Cancer Incidence Surveillance System with Medicare, Medicaid,
and Clinical Data from Home Health Care and Long Term Care Assessment
Instruments: Paving the Way for New Research Endeavors in Geriatric Oncology.
AB - This study describes the Ohio Cancer-Aging Linked Database, which mirrors in
structure the linked Surveillance, Epidemiology, and End-Results (SEER)-Medicare
files, but also incorporates data from Medicaid enrollment and claims files, the
home health care (HHC) Outcome Assessment Information Set (OASIS), and the long
term care (LTC) Minimum Data Set (MDS). This article also discusses the potential
uses of this database, particularly in addressing new research questions emerging
from the nascent and rapidly developing field of geriatric oncology.
PMID- 25132915
TI - SEGMENTATION OF MITOCHONDRIA IN ELECTRON MICROSCOPY IMAGES USING ALGEBRAIC
CURVES.
AB - High-resolution microscopy techniques have been used to generate large volumes of
data with enough details for understanding the complex structure of the nervous
system. However, automatic techniques are required to segment cells and
intracellular structures in these multi-terabyte datasets and make anatomical
analysis possible on a large scale. We propose a fully automated method that
exploits both shape information and regional statistics to segment irregularly
shaped intracellular structures such as mitochondria in electron microscopy (EM)
images. The main idea is to use algebraic curves to extract shape features
together with texture features from image patches. Then, these powerful features
are used to learn a random forest classifier, which can predict mitochondria
locations precisely. Finally, the algebraic curves together with regional
information are used to segment the mitochondria at the predicted locations. We
demonstrate that our method outperforms the state-of-the-art algorithms in
segmentation of mitochondria in EM images.
PMID- 25132913
TI - Expression of senescence-associated microRNAs and target genes in cellular aging
and modulation by tocotrienol-rich fraction.
AB - Emerging evidences highlight the implication of microRNAs as a
posttranscriptional regulator in aging. Several senescence-associated microRNAs
(SA-miRNAs) are found to be differentially expressed during cellular senescence.
However, the role of dietary compounds on SA-miRNAs remains elusive. This study
aimed to elucidate the modulatory role of tocotrienol-rich fraction (TRF) on SA
miRNAs (miR-20a, miR-24, miR-34a, miR-106a, and miR-449a) and established target
genes of miR-34a (CCND1, CDK4, and SIRT1) during replicative senescence of human
diploid fibroblasts (HDFs). Primary cultures of HDFs at young and senescent were
incubated with TRF at 0.5 mg/mL. Taqman microRNA assay showed significant
upregulation of miR-24 and miR-34a and downregulation of miR-20a and miR-449a in
senescent HDFs (P < 0.05). TRF reduced miR-34a expression in senescent HDFs and
increased miR-20a expression in young HDFs and increased miR-449a expression in
both young and senescent HDFs. Our results also demonstrated that ectopic
expression of miR-34a reduced the expression of CDK4 significantly (P < 0.05).
TRF inhibited miR-34a expression thus relieved its inhibition on CDK4 gene
expression. No significant change was observed on the expression of CCND1, SIRT1,
and miR-34a upstream transcriptional regulator, TP53. In conclusion tocotrienol
rich fraction prevented cellular senescence of human diploid fibroblasts via
modulation of SA-miRNAs and target genes expression.
PMID- 25132912
TI - New insights into the role of mitochondrial dynamics and autophagy during
oxidative stress and aging in the heart.
AB - The heart is highly sensitive to the aging process. In the elderly, the heart
tends to become hypertrophic and fibrotic. Stiffness increases with ensuing
systolic and diastolic dysfunction. Aging also affects the cardiac response to
stress. At the molecular level, the aging process is associated with accumulation
of damaged proteins and organelles, partially due to defects in protein quality
control systems. The accumulation of dysfunctional and abnormal mitochondria is
an important pathophysiological feature of the aging process, which is associated
with excessive production of reactive oxygen species. Mitochondrial fusion and
fission and mitochondrial autophagy are crucial mechanisms for maintaining
mitochondrial function and preserving energy production. In particular,
mitochondrial fission allows for selective segregation of damaged mitochondria,
which are afterward eliminated by autophagy. Unfortunately, recent evidence
indicates that mitochondrial dynamics and autophagy are progressively impaired
over time, contributing to the aging process. This suggests that restoration of
these mechanisms could delay organ senescence and prevent age-associated cardiac
diseases. Here, we discuss the current understanding of the close relationship
between mitochondrial dynamics, mitophagy, oxidative stress, and aging, with a
particular focus on the heart.
PMID- 25132917
TI - Endoscopic retrograde cholangiopancreatography in patients with altered anatomy:
How to deal with the challenges?
AB - Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically
altered anatomy is challenging. Several operative interventions of both the
gastrointestinal tract and the biliary and/or pancreatic system lead to altered
anatomy, rendering ERCP more difficult or even impossible with a conventional
side-viewing duodenoscope. Adapted endoscopes are available to reach the
biliopancreatic system and to perform ERCP in patients with altered anatomy.
However, both technical difficulties and complications determine the procedure's
success. Different technical approaches have been described and are highly
dependent on local expertise and endoscopic equipment. Standardized practical
guidelines are currently unavailable. This review focuses on the challenges
encountered during ERCP in patients with altered anatomy and how to deal with
them. The first challenge is reaching the papilla or the
bilioenteric/pancreatoenteric anastomosis in the patient with postoperative
altered anatomy. The second challenge is the cannulation of the biliopancreatic
system and performing all conventional ERCP interventions and the third challenge
is the control of possible complications. The available literature data on this
topic is reviewed and illustrated with clinical cases.
PMID- 25132916
TI - New aspects of modern endoscopy.
AB - The prognosis for patients with malignancies of the gastrointestinal-tract is
strictly dependent on early detection of premalignant and malignant lesions.
However, small, flat or depressed neoplastic lesions remain difficult to detect
with these technologies thereby limiting their value for polyp and cancer
screening. At the same time computer and chip technologies have undergone major
technological changes which have greatly improved endoscopic diagnostic
investigation. New imaging modalities and techniques are very notable aspects of
modern endoscopy. Chromoendoscopy or filter-aided colonoscopy (virtual
chromoendoscopy) with high definition endoscopes is able to enhance the detection
and characterization of lesions. Finally, confocal laser endomicroscopy provides
histological confirmation of the presence of neoplastic changes. The developing
techniques around colonoscopy such as the retro-viewing colonoscope, the balloon
colonoscope or the 330-degrees-viewing colonoscope try to enhance the efficacy by
reducing the adenoma miss rate in right-sided, non-polypoid lesions. Colon
capsule endoscopy is limited to identifying cancer and not necessarily small
adenomas. Preliminary attempts have been made to introduce this technique in
clinical routine.
PMID- 25132918
TI - Continued evidence for safety of endoscopic retrograde cholangiopancreatography
during pregnancy.
AB - AIM: To report the safety of continued use of endoscopic retrograde
cholangiopancreatography (ERCP) during pregnancy at various maternal ages.
METHODS: A retrospective chart review of pregnant patients who underwent ERCP at
a tertiary academic center was undertaken between 2002 and 2012. Pertinent past
medical history and initial presenting laboratory data were collected. Review of
the procedure note for each ERCP performed provided documentation of lead
shielding, type of sedation, fluoroscopy time, and post-procedure complications.
Patients' clinical courses were reviewed until the time of delivery and pregnancy
complications with fetal outcomes were examined. Data was stratified based upon
the mother's age at the time of ERCP: 18-21, 22-29, and >= 30 years of age.
RESULTS: Twenty pregnant patients who underwent ERCP between 2002 and 2012 were
identified. The mean age at the time of ERCP was 26.4 years (18-38 years) and the
average trimester was the second. The indications for ERCP were
choledocholithiasis in 17 patients, gallstone pancreatitis in 2 patients, and
cholangitis in 1 patient. The mean fluoroscopy time of ERCP was 3.8 min (0.3-23.6
min). Sphincterotomy was performed in 18 patients with therapeutic intent and not
as a prophylactic measure to prevent recurrences. Clinical documentation of use
of protective shielding was found in only 8 notes (40%). Post procedure
complications were limited to two cases of post-ERCP pancreatitis (10%). Elective
cholecystectomy was performed shortly after ERCP in 11 of the pregnant patients.
Birth records were available for 16 patients, of which 15 had full-term
pregnancies. Cesarean sections were performed in 5 (31%) patients. Term birth
weight was greater than 2500 g in all cases except one in which the mother had a
known hypercoagulable state. CONCLUSION: ERCP during pregnancy is both safe and
efficacious regardless of maternal age or trimester.
PMID- 25132919
TI - Virtual chromoendoscopy in small bowel capsule endoscopy: New light or a cast of
shadow?
AB - AIM: To evaluate whether virtual chromoendoscopy can improve the delineation of
small bowel lesions previously detected by conventional white light small bowel
capsule endoscopy (SBCE). METHODS: Retrospective single center study. One hundred
lesions selected from forty-nine consecutive conventional white light SBCE (SBCE
WL) examinations were included. Lesions were reviewed at three Flexible Spectral
Imaging Color Enhancement (FICE) settings and Blue Filter (BF) by two
gastroenterologists with experience in SBCE, blinded to each other's findings,
who ranked the quality of delineation as better, equivalent or worse than
conventional SBCE-WL. Inter-observer percentage of agreement was determined and
analyzed with Fleiss Kappa (kappa) coefficient. Lesions selected for the study
included angioectasias (n = 39), ulcers/erosions (n = 49) and villous
edema/atrophy (n = 12). RESULTS: Overall, the delineation of lesions was improved
in 77% of cases with FICE 1, 74% with FICE 2, 41% with FICE 3 and 39% with the
BF, with a percentage of agreement between investigators of 89% (kappa = 0.833),
85% (kappa = 0.764), 66% (kappa = 0.486) and 79% (kappa = 0.593), respectively.
FICE 1 improved the delineation of 97.4% of angioectasias, 63.3% of
ulcers/erosions and 66.7% of villous edema/atrophy with a percentage of agreement
of 97.4% (kappa = 0.910), 81.6% (kappa = 0.714) and 91.7% (kappa = 0.815),
respectively. FICE 2 improved the delineation of 97.4% of angioectasias, 57.1% of
ulcers/erosions and 66.7% of villous edema/atrophy, with a percentage of
agreement of 89.7% (kappa = 0.802), 79,6% (kappa = 0.703) and 91.7% (kappa =
0.815), respectively. FICE 3 improved the delineation of 46.2% of angioectasias,
24.5% of ulcers/erosions and none of the cases of villous edema/atrophy, with a
percentage of agreement of 53.8% [kappa = not available (NA)], 75.5% (kappa = NA)
and 66.7% (kappa = 0.304), respectively. The BF improved the delineation of 15.4%
of angioectasias, 61.2% of ulcers/erosions and 25% of villous edema/atrophy, with
a percentage of agreement of 76.9% (kappa = 0.558), 81.6% (kappa = 0.570) and
25.0% (kappa = NA), respectively. CONCLUSION: Virtual chromoendoscopy can improve
the delineation of angioectasias, ulcers/erosions and villous edema/atrophy
detected by SBCE, with almost perfect interobserver agreement for FICE 1.
PMID- 25132921
TI - Endoscopic ultrasound-guided drainage of pelvic abscess: A case series of 8
patients.
AB - AIM: To show the safety and effectiveness of endoscopic ultrasound (EUS)-guided
drainage of pelvic abscess that were inaccessible for percutaneous drainage.
METHODS: Eight consecutive patients with pelvic abscess that were not amenable to
drainage under computed tomography (CT) guidance were referred for EUS-guided
drainage. The underlying cause of the abscesses included diverticulitis in 4,
postsurgical surgical complications in 2, iatrogenic after enema in 1, and
Crohn's disease in 1 patient. Abscesses were all drained under EUS guidance via a
transrectal or transsigmoidal approach. RESULTS: EUS-guided placement of one or
two 7 Fr pigtail stents was technically successful and uneventful in all 8
patients (100%). The abscess was perisigmoidal in 2 and was multilocular in 4
patients. All procedures were performed under conscious sedation and without
fluoroscopic monitoring. Fluid samples were successfully retrieved for
microbiological studies in all cases and antibiotic policy was adjusted according
to culture results in 5 patients. Follow-up CT showed complete recovery and
disappearance of abscess. The stents were retrieved by sigmoidoscopy in only two
patients and had spontaneously migrated to outside in six patients. All drainage
procedures resulted in a favourable clinical outcome. All patients became
afebrile within 24 h after drainage and the mean duration of the postprocedure
hospital stay was 8 d (range 4-14). Within a median follow up period of 38 mo
(range 12-52) no recurrence was reported. CONCLUSION: We conclude that EUS-guided
drainage of pelvic abscesses without fluoroscopic monitoring is a minimally
invasive, safe and effective approach that should be considered in selected
patients.
PMID- 25132920
TI - Evaluation of diagnostic cytology via endoscopic naso-pancreatic drainage for
pancreatic tumor.
AB - AIM: To evaluate the usefulness of cytology of the pancreatic juice obtained via
the endoscopic naso-pancreatic drainage tube (ENPD-C). METHODS: ENPD was
performed in cases where a diagnosis could not be made other than by using
endoscopic retrograde cholangiopancreatography and in cases of pancreatic
neoplasms or cystic tumors, including intraductal papillary mucinous neoplasm
(IPMN) suspected to have malignant potential. 35 patients (21 males and 14
females) underwent ENPD between January 2007 and June 2013. The pancreatic duct
was imaged and the procedure continued in one of ENPD-C or ENPD-C plus brush
cytology (ENPD-BC). We checked the cytology result and the final diagnosis.
RESULTS: The mean patient age was 69 years (range, 48-86 years). ENPD-C was
performed in 24 cases and ENPD-C plus brush cytology (ENPD-BC) in 11 cases. The
ENPD tube was inserted for an average of 3.5 d. The final diagnosis was confirmed
on the basis of the resected specimen in 18 cases and of follow-up findings at
least 6 mo after ENPD in the 18 inoperable cases. Malignancy was diagnosed in 21
cases and 14 patients were diagnosed as having a benign condition. The ratios of
class V/IV:III:II/I findings were 7:7:7 in malignant cases and 0:3:11 in benign
cases. The sensitivity and specificity for all patients were 33.3% and 100%,
respectively. The cytology-positive rate was 37.5% (6/16) for pancreatic cancer.
For IPMN cases, the sensitivity and specificity were 33% and 100%, respectively.
CONCLUSION: Sensitivity may be further increased by adding brush cytology.
Although we can diagnosis cancer in cases of a positive result, the accuracy of
ENPD-C remains unsatisfactory.
PMID- 25132922
TI - Bowel preparation for colonoscopy using standard vs reduced doses of sodium
phosphate: A single-blind randomized controlled study.
AB - AIM: To evaluate the efficacy of a colonoscopy preparation that utilizes a
reduced dose of sodium phosphate (NaP) and an adjunct. METHODS: Sixty-two
patients requiring screening colonoscopies were studied. Each patient was
randomly allocated to receive either 50 NaP tablets (50 g) or 30 NaP tablets (30
g) with 10 mL of 0.75% sodium picosulfate for bowel preparation. NaP was
administered at a rate of five tablets (5 g) or three tablets (3 g) every 15 min
with 200 mL of water, beginning five to six hours before colonoscopy. The sodium
picosulfate was administered with 200 mL of water on the night before the
procedure. Both groups were compared in term of the efficacies of colonic
cleansing, the time required for completion of the bowel preparation, and
acceptability of the preparation. RESULTS: Sixty patients (n = 30 for each group)
were analyzed. The cleansing efficacy tended to be higher in the 30 g NaP plus
sodium picosulfate group as assessed by the mean total Ottawa scale score (50 g
NaP 6.70 +/- 1. 42 vs 30 g NaP plus sodium picosulfate 6.17 +/- 1.18 P = 0.072).
The mean time for bowel preparation tended to be shorter in the 30 g NaP plus
sodium picosulfate group (50 g NaP 189.9 +/- 64.0 min vs 30 g NaP plus sodium
picosulfate 161.8 +/- 57.6 min, P = 0.065). There were no significant differences
between the two groups in the acceptability of the preparations (50 g NaP 83.3%
vs 30 g NaP plus sodium picosulfate 86.7%, P = 0.500). There were no adverse
events related to bowel preparation in either of the groups. CONCLUSION: The
colonoscopy preparation that utilized 30 g NaP with sodium picosulfate was
comparable to that utilizing 50 g NaP. This novel bowel preparation might be
useful before colonoscopy.
PMID- 25132923
TI - Lymphoepithelioma-like esophageal carcinoma with macroscopic reduction.
AB - Esophageal lymphoepithelioma-like carcinoma (LELC) is extremely rare. We report
the first case of esophageal LELC showing macroscopic reduction. A 67-year-old
male presented with dysphagia and, by endoscopic examination, was found to have a
significantly raised tumor of 10 mm in diameter in the thoracic esophagus. The
biopsied material showed esophageal cancer. We performed endoscopic submucosal
dissection. However, the tumor became flattened, similar to a scar, in only 2 mo.
Histologically, the carcinoma cells had infiltrated the submucosal layer.
Prominent infiltration of T lymphoid cells that stained positive for CD8 was
observed around the carcinoma cells. Therefore, this lesion was considered to be
an LELC with poorly differentiated squamous cells. Because the margin was
positive, an esophagectomy was performed. Carcinoma cells were detected in the
neck in one lymph node. The staging was T1N0M1b. However, the patient has been
well, without adjuvant therapy or recurrence, for more than 5 years.
PMID- 25132924
TI - Esophageal cancer management controversies: Radiation oncology point of view.
AB - Esophageal cancer treatment has evolved from single modality to trimodality
therapy. There are some controversies of the role, target volumes and dose of
radiotherapy (RT) in the literature over decades. The present review focuses
primarily on RT as part of the treatment modalities, and highlight on the RT
volume and its dose in the management of esophageal cancer. The randomized
adjuvant chemoradiation (CRT) trial, intergroup trial (INT 0116) enrolled 559
patients with resected adenocarcinoma of the stomach or gastroesophageal
junction. They were randomly assigned to surgery plus postoperative CRT or
surgery alone. Analyses show robust treatment benefit of adjuvant CRT in most
subsets for postoperative CRT. The Chemoradiotherapy for Oesophageal Cancer
Followed by Surgery Study (CROSS) used a lower RT dose of 41.4 Gray in 23
fractions with newer chemotherapeutic agents carboplatin and paclitaxel to
achieve an excellent result. Target volume of external beam radiation therapy and
its coverage have been in debate for years among radiation oncologists. Pre
operative and post-operative target volumes are designed to optimize for disease
control. Esophageal brachytherapy is effective in the palliation of dysphagia,
but should not be given concomitantly with chemotherapy or external beam RT. The
role of brachytherapy in multimodality management requires further investigation.
On-going studies of multidisciplinary treatment in locally advanced cancer
include: ZTOG1201 trial (a phase II trial of neoadjuvant and adjuvant CRT) and
QUINTETT (a phase III trial of neoadjuvant vs adjuvant therapy with quality of
life analysis). These trials hopefully will shed more light on the future
management of esophageal cancer.
PMID- 25132925
TI - Endoscopic assessment and management of early esophageal adenocarcinoma.
AB - Esophageal carcinoma affects more than 450000 people worldwide and the incidence
is rapidly increasing. In the United States and Europe, esophageal adenocarcinoma
has superseded esophageal squamous cell carcinoma in its incidence. Esophageal
cancer has a high mortality rates secondary to the late presentation of most
patients at advanced stages. Endoscopic screening is recommended for patients
with multiple risk factors for cancer in Barrett's esophagus. These risk factors
include chronic gastroesophageal reflux disease, hiatal hernia, advanced age,
male sex, white race, cigarette smoking, and obesity. The annual risk of
esophageal cancer is approximately 0.25% for patients without dysplasia and 6%
for patients with high-grade dysplasia. Twenty percent of all esophageal
adenocarcinoma in the United States is early stage with disease confined to the
mucosa or submucosa. The significant morbidity and mortality of esophagectomy
make endoscopic treatment an attractive option. The American Gastroenterological
Association recommends endoscopic eradication therapy for patients with high
grade dysplasia. Endoscopic modalities for treatment of early esophageal
adenocarcinoma include endoscopic resection techniques and endoscopic ablative
techniques such as radiofrequency ablation, photodynamic therapy and
cryoablation. Endoscopic therapy should be precluded to patients with no evidence
of lymphovascular invasion. Local tumor recurrence is low after endoscopic
therapy and is predicted by poor differentiation of tumor, positive lymph node
and submucosal invasion. Surgical resection should be offered to patients with
deep submucosal invasion.
PMID- 25132927
TI - Neuroendocrine tumors of the gastrointestinal tract: Case reports and literature
review.
AB - Neuroendocrine tumors (NET) previously called carcinoid tumors are neoplasms of
enterochromaffin/neuroendocrine cell origin which display neurosecretory capacity
that may result in the carcinoid syndrome. The annual incidence of patients with
NET is 8.4 per 100000; yet many NET remain asymptomatic and clinically
undetected. A majority of NET follows a benign course; however, some will display
malignant characteristics. NET most commonly occur in the gastrointestinal tract
(67%) and bronchopulmonary system (25%). Gastrointestinal NET occur within the
stomach, small intestine, liver, and rectum. We report a retrospective study of
11 subjects: Eight with benign carcinoid tumors: duodenal bulb (n = 2), terminal
ileum (n = 1), sigmoid colon (n = 2), and rectum (n = 3); three with malignant
carcinoid: liver (n = 1) and intra-abdominal site (n = 2). The diagnosis,
endoscopic images, outcome, treatment and review of the literature are presented.
PMID- 25132928
TI - Matrix Degradative Enzymes and Their Inhibitors during Annular Inflammation:
Initial Step of Symptomatic Intervertebral Disc Degeneration.
AB - OBJECTIVE: Symptomatic disc degeneration develops from inflammatory reactions in
the annulus fibrosus (AF). Although inflammatory mediators during annular
inflammation have been studied, the roles of matrix metalloproteinases (MMPs) and
their inhibitors have not been fully elucidated. In this study, we evaluated the
production of MMPs and tissue inhibitors of metalloproteinase (TIMPs) during
annular inflammation using an in vitro co-culture system. We also examined the
effect of notochordal cells on annular inflammation. METHODS: Human AF (hAF)
pellet was co-cultured for 48 hours with phorbol myristate acetate-stimulated
macrophage-like THP-1 cells. hAF pellet and conditioned media (CM) from co
cultured cells were assayed for MMPs, TIMPs, and insulin-like growth factor (IGF)
1 levels using real-time reverse-transcriptase polymerase chain reaction and
enzyem-linked immunosorbent assay. To evaluate whether notochordal cells affected
MMPs or TIMPs production on annular inflammation, hAF co-cultured with
notochordal cells from adult New Zealand White rabbits, were assayed. RESULTS:
MMP-1, -3, -9; and TIMP-1 levels were significantly increased in CM of hAF co
cultured with macrophage-like cells compared with hAF alone, whereas TIMP-2 and
IGF-1 levels were significantly decreased (p<0.05). After macrophage exposure,
hAF produced significantly more MMP-1 and -3 and less TIMP-1 and -2. Interleukin
1beta stimulation enhanced MMP-1 and -3 levels, and significantly diminished TIMP
2 levels. Co-culturing with rabbit notochordal cells did not significantly
influence MMPs and TIMPs production or COL1A2 gene expression. CONCLUSION: Our
results indicate that macrophage-like cells evoke annular degeneration through
the regulation of major degradative enzymes and their inhibitors, produced by
hAF, suggesting that the selective regulation of these enzymes provides future
targets for symptomatic disc degeneration therapy.
PMID- 25132926
TI - In vitro effects of polyphenols on colorectal cancer cells.
AB - AIM: To investigate the effects of quercetin and genistein on colon cancer cell
proliferation and their estrogen receptor beta (ERbeta) expression. METHODS:
Colon cancer cells were stably transfected with a mammalian expression vector to
overexpress ERbeta (HCT8-beta8-expressing cells) or a control vector (HCT8
pSV2neo-expressing cells). The proliferation of these cells was examined after
treatment with quercetin or genistein (5-100 MUmol/L), or 10 nmol/L 17beta
estradiol (17beta-E2). Cell viability was examined by acridine orange staining
following treatments for 48 or 144 h. Effects of quercetin and genistein on
ERbeta transcriptional transactivation were examined by luciferase activity in
HCT8-beta8-expressing cells transiently transfected with a pEREtkLUC reporter
vector. In addition, the regulation of ERbeta transcription by phytoestrogens and
17beta-E2 was examined by quantitative polymerase chain reaction. RESULTS:
Proliferation of HCT8-beta8-expressing cells was not reduced low doses (5
MUmol/L) of quercetin and genistein, while it was reduced at 25-50 MUmol/L with
an effect similar to 10 nmol/L 17beta-E2. Treatment with doses of phytoestrogens
>= 75 MUmol/L completely blocked cell growth and reduced overall cell counts,
however no effects at any dose were observed in HCT8-pSV2neo-expressing cells.
These results were supported by viability staining that revealed acridine orange
stained lysosomes with high doses or extended treatment periods. Genistein and
quercetin (50 MUmol/L) significantly increased ER-responsive luciferase activity
similar to 10 nmol/L 17beta-E2 (P < 0.05). Furthermore, genistein and quercetin
(50 MUmol/L), as well as 10 nmol/L 17beta-E2 significantly increased ERbeta mRNA
levels in HCT8-beta8-expressing cells (P < 0.05). In addition, treatment of HCT8
pSV2neo-expressing cells with 50 umol/L quercetin or 10 nmol/L 17beta-E2
significantly increased ERbeta mRNA levels compared to untreated controls (P <
0.05), though the absolute levels were much lower than in HCT8-beta8-expressing
cells. CONCLUSION: The antitumorigenic effects of the phytoestrogenic compounds
quercetin and genistein on colon cancers cells occur through ERbeta activity and
expression.
PMID- 25132929
TI - Microanatomy and histological features of central myelin in the root exit zone of
facial nerve.
AB - OBJECTIVE: The aim of this study was to evaluate the microanatomy and
histological features of the central myelin in the root exit zone of facial
nerve. METHODS: Forty facial nerves with brain stem were obtained from 20
formalin fixed cadavers. Among them 17 facial nerves were ruined during
preparation and 23 root entry zone (REZ) of facial nerves could be examined. The
length of medial REZ, from detach point of facial nerve at the brain stem to
transitional area, and the thickness of glial membrane of central myelin was
measured. We cut brain stem along the facial nerve and made a tissue block of
facial nerve REZ. Each tissue block was embedded with paraffin and serially
sectioned. Slices were stained with hematoxylin and eosin (H&E), periodic acid
Schiff, and glial fibrillary acid protein. Microscopy was used to measure the
extent of central myelin and thickness of outer glial membrane of central myelin.
Thickness of glial membrane was examined at two different points, the thickest
area of proximal and distal REZ. RESULTS: Special stain with PAS and GFAP could
be differentiated the central and peripheral myelin of facial nerve. The length
of medial REZ was mean 2.6 mm (1.6-3.5 mm). The glial limiting membrane of brain
stem is continued to the end of central myelin. We called it glial sheath of REZ.
The thickness of glial sheath was mean 66.5 um (40-110 um) at proximal REZ and
7.4 um (5-10 um) at distal REZ. CONCLUSION: Medial REZ of facial nerve is mean
2.6 mm in length and covered by glial sheath continued from glial limiting
membrane of brain stem. Glial sheath of central myelin tends to become thin
toward transitional zone.
PMID- 25132930
TI - Direct lateral lumbar interbody fusion: clinical and radiological outcomes.
AB - OBJECTIVE: According to the recent development of minimally invasive spinal
surgery, direct lumbar interbody fusion (DLIF) was introduced as an effective
option to treat lumbar degenerative diseases. However, comprehensive results of
DLIF have not been reported in Korea yet. The object of this study is to
summarize radiological and clinical outcomes of our DLIF experience. METHODS: We
performed DLIF for 130 patients from May 2011 to June 2013. Among them, 90
patients, who could be followed up for more than 6 months, were analyzed
retrospectively. Clinical outcomes were compared using visual analog scale (VAS)
score and Oswestry Disability Index (ODI). Bilateral foramen areas, disc height,
segmental coronal and sagittal angle, and regional sagittal angle were measured.
Additionally, fusion rate was assessed. RESULTS: A total of 90 patients, 116
levels, were underwent DLIF. The VAS and ODI improved statistically significant
after surgery. All the approaches for DLIF were done on the left side. The left
and right side foramen area changed from 99.5 mm(2) and 102.9 mm(2) to 159.2
mm(2) and 151.2 mm(2) postoperatively (p<0.001). Pre- and postoperative segmental
coronal and sagittal angles changed statistically significant from 4.1 degrees
and 9.9 degrees to 1.1 degrees and 11.1 degrees . Fusion rates of 6 and 12
months were 60.9% and 87.8%. Complications occurred in 17 patients (18.9%).
However, most of the complications were resolved within 2 months. CONCLUSION:
DLIF is not only effective for indirect decompression and deformity correction
but also shows satisfactory mechanical stability and fusion rate.
PMID- 25132931
TI - Comparison of outcomes after atlantoaxial fusion with transarticular screws and
screw-rod constructs.
AB - OBJECTIVE: The purpose of this study was to compare the radiological and
neurological outcomes between two atlantoaxial fusion method for atlantoaxial
stabilization; C1 lateral mass-C2 pedicle screws (screw-rod constructs, SRC)
versus C1-2 transarticular screws (TAS). METHODS: Forty-one patients in whom
atlantoaxial instability was treated with atlantoaxial fixation by SRC group (27
patients, from March 2005 to May 2011) or TAS group (14 patients, from May 2000
to December 2005) were retrospectively reviewed. Numeric rating scale (NRS) for
pain assessment, Oswestry disability index (ODI), and Frankel grade were also
checked for neurological outcome. In radiologic outcome assessment, proper screw
position and fusion rate were checked. Perioperative parameters such as blood
loss during operation, operation time, and radiation exposure time were also
reviewed. RESULTS: The improvement of NRS and ODI were not different between both
groups significantly. Good to excellent response in Frankel grade is shown
similarly in both groups. Proper screw position and fusion rate were also
observed similarly between two groups. Total bleeding amount during operation is
lesser in SRC group than TAS group, but not significantly (p=0.06). Operation
time and X-ray exposure time were shorter in SRC group than in TAS group (all
p<0.001). CONCLUSION: Both TAS and SRC could be selected as safe and effective
treatment options for C1-2 instability. But the perioperative result, which is
technical demanding and X-ray exposure might be expected better in SRC group
compared to TAS group.
PMID- 25132932
TI - A morphometric study of the lumbar interspinous space in 100 stanford university
medical center patients.
AB - OBJECTIVE: With the increased use of interspinous spacers in the treatment of
lumbar stenosis, knowledge of the geometry of the interspinous space is
important. To prevent dislodgment of an interspinous spacer, the accurate depth
and width of the interspinous space needs to be established to facilitate the
best intraoperative selection of correct spacer size. METHODS: To determine the
depth and width of the interspinous space, two methods are available which
utilize plain film and magnetic resonance imaging (MRI). Data analysis of the
interspinous depth and width was undertaken in 100 patients. RESULTS: The
standard deviations were variable, since skin thickness (zone 1) was altered by
sex and age. The difference in the zone 1 distance between adjacent interspinous
processes varied according to gender (p<0.05), but was not influenced by age
[p=0.32 by analysis of variance between groups (ANOVA)]. Zone 2, the
supraspinous, and zone 3, the interspinous ligament depths, comprise the
operative working area during insertion of an interspinous spacer. There were no
differences with regard to gender or age (p>0.05). For zones 6 and 7, the
interspinous distances at the narrowest and widest points, respectively, were
found to decrease with the aging process, but the decrease was not statistically
significant. There were no differences with regard to gender (p>0.05).
CONCLUSION: This study provides additional information on the interspinous space.
This statistical data are valuable for use in the design of interspinous spacers.
PMID- 25132933
TI - Preoperative weakness and demyelination of the corticospinal tract in meningioma
patients : changes in diffusion parameters using diffusion tensor imaging.
AB - OBJECTIVE: Differentiation of demyelination in white matter from axonal damage
can be determined using diffusion tensor imaging (DTI). In this study using
meningioma patients an attempt was made to evaluate the relationship between
preoperative weakness and the changes of diffusion parameters in the
corticospinal tract (CST) using DTI. METHODS: Twenty-six patients with meningioma
were enrolled in this study. Eleven of them suffered from objective motor
weakness and were classified as Group 1. The remaining 15 patients did not
present motor weakness and were classified as Group 2. Fiber tractography and CST
diffusion parameters were obtained using DTIStudio. The ratios (lesion side mean
value/contralateral side mean value) of CST diffusion parameters were compared
with 1.0 as a test value using a one-sample t-test. RESULTS: In Group 1,
fractional anisotropy (FA), tensor trace (TT), and radial diffusivity (RD,
lambda2 and lambda3) of the CST were significantly different between two
hemispheres, but axial diffusivity (AD, lambda1) of the CST was not significantly
different between two hemispheres. In Group 2, FA and lambda3 of CST did not
differ significantly between the hemispheres. In Group 2, TT, lambda1, and
lambda2 of CST in the ipsilateral hemisphere were significantly higher than those
of the unaffected hemisphere. However, the differences were small. CONCLUSION:
Motor weakness was related to a low FA and high TT resulting from increased RD of
the CST fibers. CST diffusion changes in patients with weakness are similar to
those for demyelination.
PMID- 25132934
TI - Endovascular Treatment of a Ruptured Posterior Inferior Cerebellar Artery
Aneurysm during Pregnancy.
AB - Aneurysmal subarachnoid hemorrhage (SAH) during pregnancy is quite rare, however
it has a high maternal mortality rate. A pregnant woman in the 16th gestational
week was admitted to our hospital with a drowsy level of consciousness. A brain
magnetic resonance (MR) image showed hemorrhage on the prepontine cistern, and
both sylvian fissures, and MR angiography and cerebral digital subtraction
angiography demonstrated an aneurysm at the left posterior inferior cerebellar
artery (PICA). We performed endovascular coil embolization attempting to minimize
radiation exposure. She was discharged with no neurologic deficit and delivered a
healthy baby by cesarean section at the 38th week of gestation. This case study
reported the shortest gestational period and this is the first report on an
aneurysmal rupture arising from PICA which was treated using an endovascular
method. Using an appropriate technique for reduced radiation exposure to the
fetus and limited alterations in maternal-fetal physiology, endovascular coil
embolization could guarantee good results in treatment of aneurysmal SAH in
pregnant women.
PMID- 25132935
TI - Acute Onset of Intracerebral Hemorrhage due to Autonomic Dysreflexia.
AB - Autonomic dysreflexia is a clinical emergency syndrome of uncontrolled
sympathetic output that can occur in patients who have a history of spinal cord
injury. Despite its frequency in spinal cord injury patients, central nervous
system complications are very rare. We report a man with traumatic high level
incomplete spinal cord injury who suffered hypertensive right thalamic hemorrhage
secondary to an episode of autonomic dysreflexia. Prompt recognition and removal
of the triggering factor, the suprapubic catheter obstruction which led to
hypertensive attack, the patient had a favorable functional outcome after the
resorption of the hematoma and effective rehabilitation programme.
PMID- 25132936
TI - Thrombosis and recanalization of small saccular cerebral aneurysm : two case
reports and a suggestion for possible mechanism.
AB - Reports of thrombosis and recanalization of cerebral aneurysm are rare. We report
two cases of small, saccular aneurysms in which spontaneous thrombosis had
occurred during the preparation for endovascular coiling. Also, we review
reported cases and propose the presumed pathogenesis.
PMID- 25132937
TI - A morphologically atypical case of atlantoaxial rotatory subluxation.
AB - A rare case of atlantoaxial rotatory subluxation occurred after pediatric
cervical spine surgery performed to remove a dumbbell-shaped meningioma at the
level of the C1/C2 vertebrae. This case is classified as a post-surgical
atlantoaxial rotatory subluxation, but has a very rare morphology that has not
previously been reported. Although there are several reports about post-surgical
atlantoaxial rotatory subluxation, an important point of this case is that it
might be directly related to the spinal cord surgery in C1/C2 level. On day 6
after surgery, the patient presented with the Cock Robin position, and a computed
tomography scan revealed a normal type of atlantoaxial rotatory subluxation.
Manual reduction was performed followed by external fixation with a neck collar.
About 7 months after the first surgery, the subluxation became severe,
irreducible, and assumed an atypical form where the anterior tubercle of C1
migrated to a cranial position, and the posterior tubercle of C1 and the
occipital bone leaned in a caudal direction. The pathogenic process suggested
deformity of the occipital condyle and bilateral C2 superior facets with
atlantooccipital subluxation. A second operation for reduction and fixation was
performed, and the subluxation was stabilized by posterior fixation. We
encountered an unusual case of a refractory subluxation that was associated with
an atypical deformity of the upper spine. The case was successfully managed by
posterior fixation.
PMID- 25132938
TI - Management of traumatic c6-7 spondyloptosis with cord compression.
AB - A case of total spondyloptosis of the cervical spine at C6-7 level with cord
compression is described in a 51-year-old male. Because the bodies of C6 and 7
were tightly locked together, cervical traction failed. Then the patient was
operated on by a posterior approach. Posterior stabilization and fusion were
performed by C4-5 lateral mass and C7-T1 pedicle screw fixation and rod
instrumentation with bridging both C4-5's rods to the C7-T1's extended ones.
After C6 total laminectomy and foraminotomy, the C6 body was returned to its
proper position. Secondly, anterior stabilization and fusion were performed by C6
7 discectomy with a screw-plate system. A postoperative lateral plain radiograph
showed good realignment. In this case, we report the clinical presentation and
discuss the surgical modalities of C6-7 total spondyloptosis and the failed close
reduction.
PMID- 25132939
TI - Post-traumatic cerebral infarction following low-energy penetrating
craniocerebral injury caused by a nail.
AB - Post-traumatic cerebral infarction (PTCI) is a secondary insult which causes
global cerebral hypoxia or hypoperfusion after traumatic brain injury, and
carries a remarkable high mortality rate. PTCI is usually caused by blunt brain
injury with gross hematoma and/or brain herniation. Herein, we present the case
of a 91-year-old male who had sustained PTCI following a low-energy penetrating
craniocerebral injury due to a nail without evidence of hematoma. The patient
survived after a decompressive craniectomy, but permanent neurological damage
occurred. This is the first case of profound PTCI following a low-energy
penetrating craniocerebral nail injury and reminds clinicians of possibility this
rare dreadful complication for care of head-injured patients.
PMID- 25132940
TI - Early surgical treatment of pronator teres syndrome.
AB - We report a rare case of pronator teres syndrome in a young female patient. She
reported that her right hand grip had weakened and development of tingling
sensation in the first-third fingers two months previous. Thenar muscle atrophy
was prominent, and hypoesthesia was also examined on median nerve territory. The
pronation test and Tinel sign on the proximal forearm were positive. Severe pinch
grip power weakness and production of a weak "OK" sign were also noted. Routine
electromyography and nerve conduction velocity showed incomplete median
neuropathy above the elbow level with severe axonal loss. Surgical treatment was
performed because spontaneous recovery was not seen one month later.
PMID- 25132941
TI - IgG4-Related Intracranial Hypertrophic Pachymeningitis : A Case Report and Review
of the Literature.
AB - Hypertrophic pachymeningitis is an uncommon disorder that causes a localized or
diffuse thickening of the dura mater. Recently, the possibility that IgG4-related
sclerosing disease may underlie some cases of intracranial hypertrophic
pachymeningitis has been suggested. We herein report the tenth case of IgG4
related intracranial hypertrophic pachymeningitis and review the previous
literature. A 45-year-old male presented with left-sided focal seizures with
generalization. Magnetic resonance imaging (MRI) revealed a diffuse thickening
and enhancement of the right convexity dura matter and falx with focal
nodularity. The surgically resected specimens exhibited the proliferation of
fibroblast-like spindle cells and an infiltration of mononuclear cells, including
predominantly plasma cells. The ratio of IgG4-positive plasma cells to the
overall IgG-positive cells was 45% in the area containing the highest
infiltration of plasma cells. On the basis of the above findings, IgG4-related
sclerosing disease arising from the dura mater was suspected. IgG4-related
sclerosing disease should be added to the pachymeningitis spectrum.
PMID- 25132942
TI - Current status of robot-assisted laparoscopic surgery in pediatric urology.
AB - Laparoscopic procedures for urological diseases in children have been proven to
be safe and effective. However, the availability of laparoscopic procedures is
still partly limited to experienced, high-volume centers because the procedures
are technically demanding. The da Vinci robot system is being used for an
increasing variety of reconstructive procedures because of the advantages of this
approach, such as motion scaling, greater optical magnification, stereoscopic
vision, increased instrument tip dexterity, and tremor filtration. Particularly
in pediatric urologic surgery, where the operational field is limited owing to
the small abdominal cavity of children, robotic surgical technology has its own
strengths. Currently, robots are used to perform most surgeries in children that
can be performed laparoscopically. In this review, we aimed to provide a
comprehensive overview of the current role of robot-assisted laparoscopic surgery
in Pediatric Urology by analyzing the published data in this field. A growing
body of evidence supports the view that robotic technology is technically
feasible and safe in pediatric urological surgery. Robotic technology provides
additional benefits for performing reconstructive urologic surgery, such as in
pyeloplasty, ureteral reimplantation, and enterocystoplasty procedures. The main
limitations to robotic surgery are its high purchase and maintenance costs and
that the cost-effectiveness of this technology remains to be validated.
PMID- 25132943
TI - Associations between presenting symptoms, clinicopathological parameters, and
prognosis in a contemporary series of patients with renal cell carcinoma.
AB - PURPOSE: To evaluate the impact of presenting symptoms on survival in a
contemporary series of patients with renal cell carcinoma (RCC). MATERIALS AND
METHODS: We prospectively recorded data on the presenting symptoms, pathology,
and RCC-specific survival of 633 consecutive RCC patients who underwent surgery
between 2003 and 2012. RESULTS: Four hundred thirty-three RCCs (68%) were
incidental, 111 (18%) were associated with local symptoms, and 89 (14%) were
associated with systemic symptoms. Among those with incidental RCC, 317 patients
(73%) were completely asymptomatic and 116 patients (27%) presented with symptoms
not related to the tumor. During a median follow-up interval of 40 months
(interquartile range: 39 to 69 months), 77 patients died from RCC. In univariate
analyses, symptom classification was significantly associated with RCC-specific
survival (p<0.001). Patients with incidental RCC and unrelated symptoms tended to
have worse prognosis than did patients who were completely asymptomatic, although
this difference was not statistically significant (p=0.057). The symptom
classification was associated with advanced TNM stages (p<0.001) and grade
(p<0.001). CONCLUSIONS: This study confirms that presenting symptoms are
associated with tumor characteristics and survival. The majority of RCCs are
diagnosed incidentally in patients without any symptoms or with symptoms not
related to RCC. Patients in the latter group tend to have a worse prognosis than
do patients who are completely asymptomatic. With the increasing number of
incidentally diagnosed RCCs, substratification of patients with incidental tumors
may be prognostically relevant.
PMID- 25132944
TI - Should we place ureteral stents in retroperitoneal laparoscopic
ureterolithotomy?: Consideration of surgical techniques and complications.
AB - PURPOSE: There is some debate over the necessity of ureteral stenting after
laparoscopic ureterolithotomy. We evaluated the need for ureteral stenting after
retroperitoneal laparoscopic ureterolithotomy (RLU). MATERIALS AND METHODS:
Between January 2009 and January 2013, 41 patients underwent RLU to remove upper
ureteral stones. The retroperitoneal approach was used in all patients by a
single surgeon. A double J (D-J) stent was placed in the first 17 patients after
the procedure but not in any of the next 24 patients. RESULTS: The mean patient
age, serum creatinine levels, and stone size were not significantly different
between the two groups. The stone-free rate was 100%. The mean operative time was
significantly shorter in the stentless group than in the stent group (59.48
minutes vs. 77.88 minutes, p<0.001). Parenteral analgesic use and anticholinergic
medication use were observed in the stent group only. The blood loss, drain
removal day, and hospital stay were not significantly different between the two
groups. No other significant complications occurred during or after the operation
in any patients. CONCLUSIONS: RLU is a safe and effective treatment modality for
large impacted ureteral stones. In this study, D-J stent placement was not
necessary after RLU. In the future, large-scale studies of RLU without D-J
stenting, especially on the frequency of the development of complications
according to the surgical technique, may be needed.
PMID- 25132945
TI - Multimodal treatments of cystine stones: an observational, retrospective single
center analysis of 14 cases.
AB - PURPOSE: To document the experiences of a single institution in evaluating the
clinical courses and treatment outcomes of patients with cystine stones.
MATERIALS AND METHODS: The clinical data of 14 patients with cystine stones who
were treated at our institution from March 1994 to July 2012 were reviewed. These
data included age at first visit, gender, family history, body mass index,
presence of a single kidney, stone locations, stone burden, routine urinalysis,
and culture. In addition, we also analyzed data on surgery, shock wave
lithotripsy, medical treatment, stone recurrence or regrowth, and overall
treatment success rates. RESULTS: The mean age of our patients at their first
visit was 19.6+/-5.0 years, and eight patients were males. The median stone
burden and mean urine pH before each surgery were 6.5 cm(2) and 6.5+/-0.9,
respectively. Two patients had a family history of cystine stones. Patients
underwent surgery an average of 2.7 times. The median interval between surgeries
was 27.3 months, and 1 open surgery, 12 percutaneous nephrolithotomies, and 25
ureterorenoscopies were performed. Potassium citrate or sodium bicarbonate was
used in nine cases. D-Penicillamine was continuously used in three patients.
Patients had an average incidence of 3.2 recurrences or regrowth of stones during
the median follow-up period of 60.5 months. CONCLUSIONS: Patients with cystine
stones have high recurrence or regrowth rates and relatively large stone burdens.
Adequate treatment schedules must therefore be established in these cases to
prevent possible deterioration of renal function.
PMID- 25132946
TI - Impact of transobturator tape treatment on overactive bladder symptoms,
particularly nocturia, in patients with mixed urinary incontinence.
AB - PURPOSE: We assessed the impact of transobturator tape (TOT) treatment on
overactive bladder (OAB) symptoms with a particular focus on nocturia in patients
with mixed urinary incontinence (MUI). MATERIALS AND METHODS: In this
retrospective cohort study, the medical records of 237 women who underwent TOT
surgery for the treatment of MUI were reviewed. Of these, 86 patients (36.4%) had
preoperative nocturia. Patients with neurological diseases or sleep disorders
that could affect the voiding pattern were excluded. Patients who were being
treated with anticholinergics and antidiuretic hormones were also excluded, which
left 70 subjects eligible for analysis. Pre- and postoperative evaluations
consisted of a physical examination, 3-day frequency-volume chart, and health
related quality of life questionnaires (King's health questionnaire, overactive
bladder symptom score, and OAB-questionnaire). RESULTS: TOT treatment resulted in
an overall significant improvement in OAB symptoms including nocturia. Frequency
volume charts revealed that TOT treatment significantly decreased the actual
number of nightly voids (ANV) and the nocturnal bladder capacity index (NBCi) in
the entire cohort. However, in a subgroup of women with nocturnal polyuria, there
was no significant change in ANV or NBCi after the sling operation. Correlation
analysis of the whole cohort revealed that the postoperative changes in NBCi
correlated positively with postoperative changes in ANV. The nocturia-persisting
group was more likely to have nocturnal polyuria and lower preoperative
functional bladder capacity compared with the nocturia-improved group (p=0.024
and p=0.023, respectively). CONCLUSIONS: Our results demonstrated that the TOT
procedure resulted in an overall significant improvement in OAB symptoms
including OAB-related nocturia in patients who presented with MUI.
PMID- 25132947
TI - Effect of histological inflammation on total and free serum prostate-specific
antigen values in patients without clinically detectable prostate cancer.
AB - PURPOSE: We are often confronted with patients in the "gray zone" (prostate
specific antigen [PSA]<10 ng/mL) whose biopsies reveal no malignancy but only
inflammation. We investigated the relationship between histological inflammation
and total PSA (tPSA), free PSA (fPSA), and percentage of free PSA (f/tPSA) levels
in patients without prostate cancer (PC). MATERIALS AND METHODS: We studied 106
men with tPSA<10 ng/mL who had undergone biopsy that was negative for PC and who
had no clinical prostatitis. Inflammation observed at biopsies was scored for
inflammation type in each biopsy core by use of a four-point scale and was then
correlated with tPSA, fPSA, and f/tPSA. RESULTS: Different patterns of
inflammation were found in each set of biopsies. Regression factor analysis was
used to form two groups according to inflammation type: more chronic and more
acute. Median tPSA, fPSA, and f/tPSA levels in the more chronic and more acute
inflammation groups were 6.4 ng/mL, 1.09 ng/mL, and 15%, and 7.3 ng/mL, 0.79
ng/mL, and l2%, respectively. A significant difference was found in fPSA
(p=0.003) and f/tPSA (p<0.001), whereas the difference in tPSA was not
significant (p=0.200). Total PSA correlated with fPSA (r=0.4, p<0.001) but not
with inflammation type (r=0.12, p>0.010). A correlation existed between
inflammation type and fPSA (r=-0.31, p=0.001) and f/tPSA (r=-0.43, p<0.001) in
that the fPSA and f/tPSA were lower in the group with more acute inflammation.
CONCLUSIONS: Subclinical inflammation has a significant influence on fPSA in
patients with tPSA<10 ng/mL but without PC or clinical prostatitis. Subclinical
inflammation is not characterized by elevated tPSA alone but also by a decreased
fPSA, a tendency similar to that in PC.
PMID- 25132948
TI - Adolescent varicocele: are somatometric parameters a cause?
AB - PURPOSE: It has been reported that varicocele is found less frequently in obese
men. Accordingly, we evaluated varicocele patients and statistically analyzed the
correlation between varicocele and somatometric parameters. MATERIALS AND
METHODS: A total of 211 patients underwent surgery for varicoceles. All patients
underwent history taking, physical examination, and scrotal ultrasound to
determine the presence and severity of varicocele. An age-matched control group
consisted of 102 patients who were found not to have varicocele according to
physical examinations and scrotal ultrasound. The age, weight, height, and body
mass index (BMI) of the two groups were compared. The statistical analyses were
performed by use of PASW Statistics ver. 18.0. A p-value of less than 0.05 was
used for statistical significance. RESULTS: In the varicocele group, the mean
age, height, weight, and BMI were 29.42+/-14.01 years, 168.53+/-9.97 cm, 62.14+/
13.17 kg, and 21.66+/-3.21 kg/m(2), respectively. The distribution of varicocele
grade was as follows: 103 (48.8%) grade III, 72 (34.1%) grade II, and 36 (17.1%)
grade I. In the control group, the mean age, height, weight, and BMI were 30.83+/
17.31 years, 161.93+/-19.83 cm, 64.69+/-17.86 kg, and 24.04+/-3.64 kg/m(2),
respectively. Analyzing these data specifically in adolescents, they showed
significant differences in age, height, and BMI (p=0.000, p=0.000, and p=0.004,
respectively) between two groups. There were no significant differences in
somatometric parameters between patients with different grades of varicocele.
CONCLUSIONS: Our results showed that patients with varicoceles were significantly
taller and had a lower BMI than did patients without varicoceles, especially
among adolescents. Carefully designed future studies may be needed.
PMID- 25132949
TI - Are clinical, laboratory, and imaging markers suitable predictors of
vesicoureteral reflux in children with their first febrile urinary tract
infection?
AB - PURPOSE: This study was conducted to determine the predictive value of clinical,
laboratory, and imaging variables for the diagnosis of vesicoureteral reflux in
children with their first febrile urinary tract infection. MATERIALS AND METHODS:
One hundred fifty-three children with their first febrile urinary tract infection
were divided into two groups according to the results of voiding
cystourethrography: 60 children with vesicoureteral reflux and 93 children
without. The sensitivity, specificity, positive and negative predictive value,
likelihood ratio (positive and negative), and accuracy of the clinical,
laboratory, and imaging variables for the diagnosis of vesicoureteral reflux were
determined. RESULTS: Of the 153 children with febrile urinary tract infection, 60
patients (39.2%) had vesicoureteral reflux. There were significant differences
between the two groups regarding fever>38C, suprapubic pain, C-reactive protein
quantitative level, number of red blood cells in the urine, and results of renal
ultrasound and dimercaptosuccinic acid renal scanning (p<0.05). There were
significant positive correlations between fever>38.2C and dimercaptosuccinic acid
renal scanning and vesicoureteral reflux. Also, there were significant positive
correlations between the erythrocyte sedimentation rate, positive urinary nitrite
test, hyaline cast, and renal ultrasound and high-grade vesicoureteral reflux.
CONCLUSIONS: This study revealed fever>38.2C and dimercaptosuccinic acid renal
scanning as the best predictive markers for vesicoureteral reflux in children
with their first febrile urinary tract infection. In addition, erythrocyte
sedimentation rate, positive urinary nitrite test, hyaline cast, and renal
ultrasound are the best predictive markers for high-grade vesicoureteral reflux.
PMID- 25132950
TI - Altered gene expression profile after exposure to transforming growth factor
beta1 in the 253J human bladder cancer cell line.
AB - PURPOSE: Transforming growth factor beta1 (TGF-beta1) inhibits the growth of
bladder cancer cells and this effect is prominent and constant in 253J bladder
cancer cells. We performed a microarray analysis to search for genes that were
altered after TGF-beta1 treatment to understand the growth inhibitory action of
TGF-beta1. MATERIALS AND METHODS: 253J bladder cancer cells were exposed to TGF
beta1 and total RNA was extracted at 6, 24, and 48 hours after exposure. The RNA
was hybridized onto a human 22K oligonucleotide microarray and the data were
analyzed by using GeneSpring 7.1. RESULTS: In the microarray analysis, a total of
1,974 genes showing changes of more than 2.0 fold were selected. The selected
genes were further subdivided into five highly cohesive clusters with high
probability according to the time-dependent expression pattern. A total of 310
genes showing changes of more than 2.0 fold in repeated arrays were identified by
use of simple t-tests. Of these genes, those having a known function were listed
according to clusters. Microarray analysis showed increased expression of
molecules known to be related to Smad-dependent signal transduction, such as SARA
and Smad4, and also those known to be related to the mitogen-activated protein
kinase (MAPK) pathway, such as MAPKK1 and MAPKK4. CONCLUSIONS: A list of genes
showing significantly altered expression profiles after TGF-beta1 treatment was
made according to five highly cohesive clusters. The data suggest that the growth
inhibitory effect of TGF-beta1 in bladder cancer may occur through the Smad
dependent pathway, possibly via activation of the extracellular signal-related
kinase 1 and Jun amino-terminal kinases Mitogen-activated protein kinase pathway.
PMID- 25132952
TI - Management of an iatrogenic injury in a crossed ectopic kidney without fusion.
AB - Crossed renal ectopia is a condition in which a kidney is located on the side
opposite of its ureteral insertion. Ninety percent of crossed ectopic kidneys are
fused to their ipsilateral uncrossed renal unit. Crossed renal ectopia without
fusion is rare, with only 62 patients reported in the literature to date. These
kidneys may suffer iatrogenic injury during an unrelated surgical intervention.
The injury, unless self-limiting, may necessitate the removal of the ectopic
kidney. We present a unique case of a dual injury, renal as well as ureteric, in
a crossed ectopic kidney without fusion that was successfully managed without
surgical excision.
PMID- 25132951
TI - Adrenal cortical scintigraphy for lateralization of bilateral adrenal nodules in
primary aldosteronism.
PMID- 25132953
TI - Evaluating the impacts of stressors of Pseudomonas syringae pathovar tomato on
the effectiveness of multi-locus variable number tandem repeat analysis and multi
locus sequence typing in microbial forensic investigations.
AB - BACKGROUND: Crops in the USA are vulnerable to natural and criminal threats
because of their widespread cultivation and lack of surveillance, and because of
implementation of growing practices such as monoculture. To prepare for
investigation and attribution of such events, forensic assays, including
determination of molecular profiles, are being adapted for use with plant
pathogens. The use of multi-locus variable number tandem repeat (VNTR) analysis
(MLVA) and multi-locus sequence typing (MLST) in investigations involving plant
pathogens may be problematic because the long lag periods between pathogen
introduction and discovery of associated disease may provide enough time for
evolution to occur in the regions of the genome employed in each assay. Thus,
more information on the stability of the loci employed in these methods is
needed. RESULTS: The MLVA fingerprints and MLST profiles were consistent
throughout the experiment, indicating that, using a specific set of primers and
conditions, MLVA and MLST typing systems reliably identify P.s. tomato DC3000.
This information is essential to forensic investigators in interpreting
comparisons between MLVA and MLST typing profiles observed in P.s. tomato
isolates. CONCLUSIONS: Our results indicate that MLVA and MLST typing systems,
utilizing the specified primers and conditions, could be employed successfully in
forensics investigations involving P.s. tomato. Similar experiments should be
conducted in the field and with other high-consequence plant pathogens to ensure
that the assays are reliable for pathogens infecting plants in their natural
environment and for organisms that may display faster rates of mutation.
PMID- 25132954
TI - Study design considerations for evaluating the efficacy and safety of pancreatic
enzyme replacement therapy in patients with cystic fibrosis.
AB - In 2006, the US FDA issued a 'Guidance for Industry' regarding submission of New
Drug Applications for pancreatic enzyme replacement therapy (PERT) products. Five
oral delayed-release PERT products have been approved by the FDA, and several
others are under development and/ or evaluation for New Drug Application
submission. We present in this paper recommendations of the Cystic Fibrosis
Foundation's Cystic Fibrosis (CF) Therapeutics Development Network and Data
Safety Monitoring Board regarding study design considerations for evaluating PERT
products in patients with CF. Careful attention to study design and accuracy of
the outcome measures has confirmed our understanding of the efficacy and safety
of PERT for the treatment of exocrine pancreatic insufficiency of CF.
PMID- 25132955
TI - Characterization and assessment of the sensitivity and resistance of a newly
established human gastrointestinal stromal tumour xenograft model to treatment
with tyrosine kinase inhibitors.
AB - BACKGROUND: Acquired resistance to tyrosine kinase inhibitors (TKIs) in
gastrointestinal stromal tumours (GISTs) is most commonly caused by secondary KIT
or PDGFRA mutations. In this study we characterize a newly established GIST
xenograft model, UZLX-GIST9, and evaluate the in vivo response of the model to
standard TKIs (imatinib, sunitinib, and regorafenib). METHODS: Tumour fragments
from a metastatic lesion of a GIST patient clinically progressing after treatment
with imatinib, sunitinib and regorafenib were engrafted in a nude,
immunodeficient mouse. Upon sequential passaging from mouse to mouse, tumour
fragments were collected for histopathological and molecular characterization.
The sensitivity of the model to treatment with TKIs was evaluated in 28 mice
[passage 2 (n = 8), passage 4 (n = 20), 41 tumours]. Mice were grouped as
follows: control (untreated), imatinib (50 mg/kg/BID), imatinib (100 mg/kg/BID),
sunitinib (40 mg/kg/QD), and regorafenib (30 mg/kg/QD). After three weeks of oral
treatment, tumours were collected for subsequent analysis. The efficacy of
treatment was assessed by tumour volume, histopathology and Western
immunoblotting. RESULTS: UZLX-GIST9 maintains the same typical morphological
features and immunohistochemical characteristics as the original patient biopsy
and expresses CD117 and DOG1. The KIT mutational profile (p.P577del + W557LfsX5+
D820G) remains the same as the original tissue sample originating from an
intraspinal metastatic site. Three week treatment with different TKIs showed that
the model is resistant to imatinib. Sunitinib induces tumour growth delay and
regorafenib reduces the tumour burden by 30% as compared to control animals.
While none of the TKIs had a significant effect on cell proliferation or cell
survival, a remarkable increase of necrosis and significant reduction of
microvessel density was observed under sunitinib and regorafenib. Western
immunoblotting showed a mild reduction in KIT and AKT activation only in
regorafenib treated tumours. CONCLUSIONS: We established a novel human GIST
xenograft, UZLX-GIST9, harbouring KIT exon 11 and 17 mutations and maintaining
the pheno-and genotype of the original tumour. UZLX-GIST9 shows different levels
of response to standard TKIs. This model will help to study TKI resistance and to
explore novel treatment approaches for patients with TKI-resistant GIST.
PMID- 25132957
TI - Systemic fungal infection in a dog: a unique case in Ireland.
AB - A three year old male entire Staffordshire bull terrier was referred to
University College Dublin Veterinary Hospital, with a two week history of fever,
inflammation of the right hock, lameness on the right hindlimb, peripheral
lymphadenopathy and gastrointestinal signs (vomiting and diarrhoea). For the
preceding three months the dog had been treated for atopic dermatitis with oral
ciclosporin (5 mg/kg, PO, q 24 hours). Cytological analysis of the affected lymph
nodes demonstrated fungal-like organisms predominantly contained within
macrophages. Subsequent fungal culture and microscopic identification confirmed
the presence of a Byssochlamys sp. This fungus is a saprophytic organism which
has been associated with mycotoxin production. It has not previously been
identified as a cause of systemic infection in animals or humans. Ciclosporin was
discontinued, and a second generation triazole, voriconazole prescribed at a dose
of 6 mg/kg for the first two doses, and continued at 3 mg/kg every 12 hours for
six months. There was an excellent response. Follow-up examination five weeks
after treatment was completed confirmed remission of the disease. The dog remains
alive and well three years later. The present case represents an unusual fungal
infection in a dog secondary to immunosuppressive therapy with ciclosporin. Such
a possibility should be considered in animals presenting with signs consistent
with systemic infection when receiving immunosuppressive medication.
PMID- 25132956
TI - Hyperbaric oxygen therapy fails to reduce hydrocephalus formation following
subarachnoid hemorrhage in rats.
AB - BACKGROUND & PURPOSE: Approximately 40% of hemorrhagic stroke survivors develop
hydrocephalus. Hyperbaric oxygen (HBO) has been shown to be anti-inflammation
following experimental stroke; however, its effect upon post-hemorrhagic
hydrocephalus formation is not known. The objective of this study is to
investigate whether HBO therapy can effectively reduce hydrocephalus formation
and improve neurobehavioral functions in a rat model of subarachnoid hemorrhage
(SAH). METHOD: Thirty-eight male Sprague-Dawley rats (300-320 g) rats survived
for 21 days from SAH by endovascular perforation or sham surgery were used. At 24
hours after SAH, HBO (3 atmospheres absolute) or normobaric oxygen (NBO)
administrated for 1 hour once daily for a total of 7 days. Wire hanging and
rotarod testing were conducted at 14 days after SAH, and cognitive functions were
evaluated via the Morris water maze, between day 17 to day 21 after surgery. At
day 21, rats were sacrificed and cerebroventricular volumes were measured
histologically. RESULTS: Hydrocephalus exacerbated neurological deficits after
SAH, and HBO multiple treatment tendentially improved the neurobehavioral
functions. Spatial learning and memory deficits were noticed after SAH, and rats
with hydrocephalus showed worse learning and memory abilities and HBO treatment
showed a minor improvement. In the SAH group (room air) 4 rats showed an
increased ventricular volume at day 21 after SAH-induction (n = 10). HBO or NBO
therapy did not alter the occurrence of hydrocephalus after SAH, as 4 rats in
each of these groups showed an increased ventricular volume (n = 10 per group).
CONCLUSION: Multiple HBO therapy does not ameliorate hydrocephalus formation in a
rat model of SAH; however, HBO tendentially improved the neurological functions
and spatial learning and memory abilities in rats with hydrocephalus.
PMID- 25132958
TI - Short- and long-term habituation of auditory event-related potentials in the rat.
AB - An auditory oddball paradigm in humans generates a long-duration cortical
negative potential, often referred to as mismatch negativity. Similar negativity
has been documented in monkeys and cats, but it is controversial whether mismatch
negativity also exists in awake rodents. To this end, we recorded cortical and
hippocampal evoked responses in rats during alert immobility under a typical
passive oddball paradigm that yields mismatch negativity in humans. The standard
stimulus was a 9 kHz tone and the deviant either 7 or 11 kHz tone in the first
condition. We found no evidence of a sustained potential shift when comparing
evoked responses to standard and deviant stimuli. Instead, we found repetition
induced attenuation of the P60 component of the combined evoked response in the
cortex, but not in the hippocampus. The attenuation extended over three days of
recording and disappeared after 20 intervening days of rest. Reversal of the
standard and deviant tones resulted is a robust enhancement of the N40 component
not only in the cortex but also in the hippocampus. Responses to standard and
deviant stimuli were affected similarly. Finally, we tested the effect of
scopolamine in this paradigm. Scopolamine attenuated cortical N40 and P60 as well
as hippocampal P60 components, but had no specific effect on the deviant
response. We conclude that in an oddball paradigm the rat demonstrates repetition
induced attenuation of mid-latency responses, which resembles attenuation of the
N1-component of human auditory evoked potential, but no mismatch negativity.
PMID- 25132959
TI - Testicular artery pseudoaneurysm: a case report.
AB - This is a case of an unusual cause of a testicular mass and the clinical features
associated with its presentation and management. The patient presented with
testicular pain and was found to have a testicular mass on ultrasound with a
central 1cm anechoic region with arterial wave-form concerning for a
pseudoaneurysm. The patient underwent orchiectomy with resolution of his
symptoms. This case highlights the presentation of testicular artery
pseudoaneurysm and outcome following orchiectomy.
PMID- 25132962
TI - Visual record of intertidal disturbance caused by drift ice in the spring on the
Atlantic coast of Nova Scotia.
AB - In the early spring of 2014, an unusually large amount of sea ice drifted from
the Gulf of St. Lawrence, where it had been produced, towards the open Atlantic
Ocean through the Cabot Strait, between Nova Scotia and Newfoundland, Canada. In
early April, significant amounts of drift ice reached the Atlantic coast of
mainland Nova Scotia. The ice floes persisted in those coastal waters for up to
16 days, depending on the location. During that time, the ice fragments caused
extensive physical disturbance in rocky intertidal communities, removing high
quantities of seaweeds and invertebrates. For example, at a location where the
ice stayed for 9 days, the loss of macroalgal and invertebrate biomass was almost
total. At a location where the ice stayed for 4 days, losses were lower, albeit
still high overall. Such a magnitude of disturbance is not common on this coast,
as sea ice had not reached the surveyed locations in the previous 4-5 years. We
suggest that the frequency of ice scour events may help to predict intertidal
community structure. This notion could be tested through multiannual surveys of
ice conditions and biological communities along the Atlantic coast of Nova
Scotia.
PMID- 25132961
TI - Colonoscopic polyp detection rate is stable throughout the workday including
evening colonoscopy sessions.
AB - OBJECTIVE: Polyp detection rate (PDR) is an accepted measure of colonoscopy
quality. Several factors may influence PDR including time of procedure and order
of colonoscopy within a session. Our unit provides evening colonoscopy lists (6-9
pm). We examined whether colonoscopy performance declines in the evening. DESIGN:
Data for all National Health Service (NHS) outpatient colonoscopies performed at
Norfolk and Norwich University Hospital in 2011 were examined. Timing,
demographics, indication and colonoscopy findings were recorded. Statistical
analysis was performed using multivariate regression. RESULTS: Data from 2576
colonoscopies were included: 1163 (45.1%) in the morning, 1123 (43.6%) in the
afternoon and 290 (11.3%) in the evening. Overall PDR was 40.80%. Males,
increasing age and successful caecal intubation were all significantly associated
with higher polyp detection. The indications 'faecal occult blood screening'
(p<0.001) and 'polyp surveillance' (p<0.001) were strongly positively associated
and 'anaemia' (p=0.01) was negatively associated with PDR. Following adjustment
for covariates, there was no significant difference in PDR between sessions.
With the morning as the reference value, the odds ratio for polyp detection in
the afternoon and evening were 0.93 (95% CI = 0.72-1.18) and 1.15 (95%CI = 0.82
1.61) respectively. PDR was not affected by rank of colonoscopy within a list,
sedation dose or trainee-involvement. CONCLUSIONS: Time of day did not affect
polyp detection rate in clinical practice. Evening colonoscopy had equivalent
efficacy and is an effective tool in meeting increasing demands for endoscopy.
Standardisation was shown to have a considerable effect as demographics,
indication and endoscopist varied substantially between sessions. Evening
sessions were popular with a younger population.
PMID- 25132960
TI - Exercise-induced arterial hypertension - an independent factor for hypertrophy
and a ticking clock for cardiac fatigue or atrial fibrillation in athletes?
AB - Background : Exercise-induced arterial hypertension (EIAH) leads to myocardial
hypertrophy and is associated with a poor prognosis. EIAH might be related to the
"cardiac fatigue" caused by endurance training. The goal of this study was to
examine whether there is any relationship between EIAH and left ventricular
hypertrophy in Ironman-triathletes. METHODS: We used echocardiography and
spiroergometry to determine the left ventricular mass (LVM), the
aerobic/anaerobic thresholds and the steady-state blood pressure of 51 healthy
male triathletes. The main inclusion criterion was the participation in at least
one middle or long distance triathlon. RESULTS: When comparing triathletes with
LVM <220g and athletes with LVM >220g there was a significant difference between
blood pressure values (BP) at the anaerobic threshold (185.2+/- 21.5 mmHg vs.
198.8 +/-22.3 mmHg, p=0.037). The spiroergometric results were: maximum oxygen
uptake (relative VO 2max) 57.3 +/-7.5ml/min/kg vs. 59.8+/-9.5ml/min/kg (p=ns).
Cut-point analysis for the relationship of BP >170 mmHg at the aerobic threshold
and the probability of LVM >220g showed a sensitivity of 95.8%, a specificity of
33.3%, with a positive predictive value of 56.8 %, a good negative predictive
value of 90%. The probability of LVM >220g increased with higher BP during
exercise (OR: 1.027, 95% CI 1.002-1.052, p= 0.034) or with higher training volume
(OR: 1.23, 95% CI 1.04 -1.47, p = 0.019). Echocardiography showed predominantly
concentric remodelling, followed by concentric hypertrophy. CONCLUSION:
Significant left ventricular hypertrophy with LVM >220g is associated with higher
arterial blood pressure at the aerobic or anaerobic threshold. The endurance
athletes with EIAH may require a therapeutic intervention to at least prevent
extensive stiffening of the heart muscle and exercise-induced cardiac fatigue.
PMID- 25132963
TI - Recent trends in airway management: we are not ready to give up fiberoptic
endoscopy.
AB - The purpose of this correspondence is to discuss recent findings related to
current trends in airway management and to discuss the utilization rates of video
laryngoscopes versus traditional techniques in USA, UK, and Canada. To highlight
the increased use of video laryngoscopes in difficult airway situations, data on
the use of alternative airway devices at our institution collected from 2008 to
2010 are presented alongside the results of previously published surveys
collected from 2002 to 2013.
PMID- 25132964
TI - Early integration of the individual student in academic activities: a novel
classroom concept for graduate education in molecular biophysics and structural
biology.
AB - BACKGROUND: A key challenge in interdisciplinary research is choosing the best
approach from a large number of techniques derived from different disciplines and
their interfaces. RESULTS: To address this challenge in the area of Biophysics
and Structural Biology, we have designed a graduate level course to teach
students insightful use of experimental biophysical approaches in relationship to
addressing biological questions related to biomolecular interactions and
dynamics. A weekly seminar and data and literature club are used to compliment
the training in class. The course contains wet-laboratory experimental
demonstration and real-data analysis as well as lectures, grant proposal
preparation and assessment, and student presentation components. Active student
participation is mandatory in all aspects of the class. Students prepare
materials for the class receiving individual and iterative feedback from course
directors and local experts generating high quality classroom presentations.
CONCLUSIONS: The ultimate goal of the course is to teach students the skills
needed to weigh different experimental approaches against each other in
addressing a specific biological question by thinking and executing academic
tasks like faculty.
PMID- 25132965
TI - The occurrence of Enterobacteriaceae producing KPC carbapenemases in a general
hospital in Curacao.
AB - BACKGROUND: Although the presence of Carbapenemase-producing Enterobacteriaceae
(CPE) are extensively documented in North and South America. CPE have not been
reported from Curacao. However, recently intercontinental spread was suggested of
a KPC carbapenemase producing Klebsiella pneumoniae in a patient in the United
Kingdom with previous admission to a hospital in Curacao in 2009. FINDINGS: After
the introduction of the CLSI 2010 revised breakpoints, seven patients with
carbapenemase-producing Enterobacteriaceae were found in a general hospital in
Curacao over a period of 16 months. Four patients carried KPC-2 positive
Klebsiella pneumoniae, ST11. Two patients carried KPC-3 positive Klebsiella
pneumoniae ST258 and one patient carried a KPC-3 positive Citrobacter freundii.
Furthermore, our Klebsiella pneumoniae KPC-2 ST11 strain was matched to the
Klebsiella pneumoniae KPC-2 ST11 strain in the United Kingdom. CONCLUSIONS:
Introduction of new laboratory methods, and adoption of new guidelines and
breakpoints led to the first detection of CPE in Curacao. By matching our
Klebsiella pneumoniae KPC-2 ST11 strain to a Klebsiella pneumoniae KPC-2 ST11
strain in the United Kingdom, we suggest that carbapenemase-producing
Enterobacteriaceae are probably more prevalent in Curacao than previously
recognized.
PMID- 25132966
TI - Development of Superoxide Dismutase Mimetic Surfaces to Reduce Accumulation of
Reactive Oxygen Species for Neural Interfacing Applications.
AB - Despite successful initial recording, neuroinflammatory-mediated oxidative stress
products can contribute to microelectrode failure by a variety of mechanisms
including: inducing microelectrode corrosion, degrading insulating/passivating
materials, promoting blood-brain barrier breakdown, and directly damaging
surrounding neurons. We have shown that a variety of anti-oxidant treatments can
reduce intracortical microelectrode-mediated oxidative stress, and preserve
neuronal viability. Unfortunately, short-term soluble delivery of anti-oxidant
therapies may be unable to provide sustained therapeutic benefits due to low bio
availability and fast clearance rates. In order to develop a system to provide
sustained neuroprotection, we investigated modifying the microelectrode surface
with an anti-oxidative coating. For initial proof of concept, we chose the
superoxide dismutase (SOD) mimetic Mn(III)tetrakis(4-benzoic acid)porphyrin
(MnTBAP). Our system utilizes a composite coating of adsorbed and immobilized
MnTBAP designed to provide an initial release followed by continued presentation
of an immobilized layer of the antioxidant. Surface modification was confirmed by
XPS and QCMB-D analysis. Antioxidant activity of composite surfaces was
determined using a Riboflavin/NitroBlue Tetrazolium (RF/NBT) assay. Our results
indicate that the hybrid modified surfaces provide several days of anti-oxidative
activity. Additionally, in vitro studies with BV-2 microglia cells indicated a
significant reduction of intracellular and extracellular reactive oxygen species
when cultured on composite MnTBAP surfaces.
PMID- 25132968
TI - Indications and outcomes in adult lung transplantation.
AB - Lung transplantation (LTx) is a treatment option for end-stage lung disease that
would be otherwise fatal for specific patient populations. The most common
indications for LTx in adults remain to be chronic obstructive pulmonary disease,
idiopathic pulmonary fibrosis, cystic fibrosis, alpha-1 antitrypsin deficiency,
and idiopathic pulmonary arterial hypertension. Recent trends include performing
re-transplantation while more patients over the age of 65 years are undergoing
LTx. Even with these tendencies, slight improvements in survival have occurred.
This article briefly reviews recent developments in adults undergoing LTx.
PMID- 25132967
TI - Directed cardiomyogenesis of autologous human induced pluripotent stem cells
recruited to infarcted myocardium with bioengineered antibodies.
AB - OBJECTIVE: Myocardial infarctions constitute a major factor contributing to non
natural mortality world-wide. Clinical trials of myocardial regenerative therapy,
currently pursued by cardiac surgeons, involve administration of stem cells into
the hearts of patients suffering from myocardial infarctions. Unfortunately,
surgical acquisition of these cells from bone marrow or heart is traumatic,
retention of these cells to sites of therapeutic interventions is low, and
directed differentiation of these cells in situ into cardiomyocytes is difficult.
The specific aims of this work were: (1) to generate autologous, human,
pluripotent, induced stem cells (ahiPSCs) from the peripheral blood of the
patients suffering myocardial infarctions; (2) to bioengineer heterospecific
antibodies (htAbs) and use them for recruitment of the ahiPSCs to infarcted
myocardium; (3) to initiate in situ directed cardiomyogenesis of the ahiPSCs
retained to infarcted myocardium. METHODS: Peripheral blood was drawn from six
patients scheduled for heart transplants. Mononuclear cells were isolated and
reprogrammed, with plasmids carrying six genes (NANOG, POU5F1, SOX2, KLF4,
LIN28A, MYC), to yield the ahiPSCs. Cardiac tissues were excised from the injured
hearts of the patients, who received transplants during orthotopic surgery. These
tissues were used to prepare in vitro models of stem cell therapy of infarcted
myocardium. The htAbs were bioengineered, which simultaneously targeted receptors
displayed on pluripotent stem cells (SSEA-4, SSEA-3, TRA-1-60, TRA-1-81) and
proteins of myocardial sarcomeres (myosin, alpha-actinin, actin, titin). They
were used to bridge the ahiPSCs to the infarcted myocardium. The retained ahiPSCs
were directed with bone morphogenetic proteins and nicotinamides to differentiate
towards myocardial lineage. RESULTS: The patients' mononuclear cells were
efficiently reprogrammed into the ahiPSCs. These ahiPSCs were administered to
infarcted myocardium in in vitro models. They were recruited to and retained at
the treated myocardium with higher efficacy and specificity, if were preceded
with the htAbs, than with isotype antibodies or plain buffers. The retained cells
differentiated into cardiomyocytes. CONCLUSIONS: The proof of concept has been
attained, for reprogramming the patients' blood mononuclear cells (PBMCs) into
the ahiPSCs, recruiting these cells to infarcted myocardium, and initiating their
cardiomyogenesis. This novel strategy is ready to support the ongoing clinical
trials aimed at regeneration of infarcted myocardium.
PMID- 25132969
TI - Pediatric lung transplantation: indications and outcomes.
AB - Lung transplantation (LTx) is a treatment option for infants and children with
untreatable and otherwise fatal pulmonary diseases. To date, over 1,800 lung
transplants have been performed, most frequently in children over the age of five
years. The most common indications for transplantation in children overall are
cystic fibrosis (CF) and idiopathic pulmonary hypertension (PH). The surfactant
protein deficiencies, other interstitial lung diseases (ILDs), and congenital
heart disease are important indications among young children and infants. Re
transplantation is an option for selected recipients with chronic allograft
rejection. Overall survival following pediatric LTx is similar to that
encountered in adult patients, with recent registry data indicating a median
survival of 4.9 years. Other outcomes such as the incidence of bronchiolitis
obliterans (BO) and the presence of key post-transplant co-morbid conditions are
also similar to the experience in adult lung transplant recipients.
PMID- 25132970
TI - Lung donor selection criteria.
AB - The criteria that define acceptable physiologic and social parameters for lung
donation have remained constant since their empiric determination in the 1980s.
These criteria include a donor age between 25-40, a arterial partial pressure of
oxygen (PaO2)/FiO2 ratio greater than 350, no smoking history, a clear chest X
ray, clean bronchoscopy, and a minimal ischemic time. Due to the paucity of organ
donors, and the increasing number of patients requiring lung transplant, finding
a donor that meets all of these criteria is quite rare. As such, many transplants
have been performed where the donor does not meet these stringent criteria. Over
the last decade, numerous reports have been published examining the effects of
individual acceptance criteria on lung transplant survival and graft function.
These studies suggest that there is little impact of the historical criteria on
either short or long term outcomes. For age, donors should be within 18 to 64
years old. Gender may relay benefit to all female recipients especially in male
to female transplants, although results are mixed in these studies. Race matched
donor/recipients have improved outcomes and African American donors convey worse
prognosis. Smoking donors may decrease recipient survival post transplant, but
provide a life saving opportunity for recipients that may otherwise remain on the
transplant waiting list. No specific gram stain or bronchoscopic findings are
reflected in recipient outcomes. Chest radiographs are a poor indicator of lung
donor function and should not adversely affect organ usage aside for concerns
over malignancy. Ischemic time greater than six hours has no documented adverse
effects on recipient mortality and should not limit donor retrieval distances.
Brain dead donors and deceased donors have equivalent prognosis. Initial
PaO2/FiO2 ratios less than 300 should not dissuade donor organ usage, although
recruitment techniques should be implemented with intent to transplant.
PMID- 25132972
TI - Ex vivo lung perfusion.
AB - Lung transplantation (LTx) is an established treatment option for eligible
patients with end-stage lung disease. Nevertheless, the imbalance between
suitable donor lungs available and the increasing number of patients considered
for LTx reflects in considerable waitlist mortality. Among potential alternatives
to address this issue, ex vivo lung perfusion (EVLP) has emerged as a modern
preservation technique that allows for more accurate lung assessment and also
improvement of lung function. Its application in high-risk donor lungs has been
successful and resulted in safe expansion of the donor pool. This article will:
(I) review the technical details of EVLP; (II) the rationale behind the method;
(III) report the worldwide clinical experience with the EVLP, including the
Toronto technique and others; (IV) finally, discuss the growing literature on
EVLP application for donation after cardiac death (DCD) lungs.
PMID- 25132973
TI - The surgical technique of bilateral sequential lung transplantation.
AB - Since the first successful lung transplant performed three decades ago, the
technique of lung transplantation has evolved with acceptable short- and long
term outcomes such that it has become the standard for those with end stage
pulmonary disease. Herein, we describe our current favored approach and discuss
some of the current areas in need of further investigation as they relate to the
technical aspects of the operation.
PMID- 25132971
TI - Immunosuppression in lung transplantation.
AB - Lung transplantation can be a life-saving procedure for those with end-stage lung
diseases. Unfortunately, long term graft and patient survival are limited by both
acute and chronic allograft rejection, with a median survival of just over 6
years. Immunosuppressive regimens are employed to reduce the rate of rejection,
and while protocols vary from center to center, conventional maintenance therapy
consists of triple drug therapy with a calcineurin inhibitor (cyclosporine or
tacrolimus), antiproliferative agents [azathioprine (AZA), mycophenolate,
sirolimus (srl), everolimus (evl)], and corticosteroids (CS). Roughly 50% of lung
transplant centers also utilize induction therapy, with polyclonal antibody
preparations [equine or rabbit anti-thymocyte globulin (ATG)], interleukin 2
receptor antagonists (IL2RAs) (daclizumab or basiliximab), or alemtuzumab. This
review summarizes these agents and the data surrounding their use in lung
transplantation, as well as additional common and novel therapies in lung
transplantation. Despite the progression of the management of lung transplant
recipients, they continue to be at high risk of treatment-related complications,
and poor graft and patient survival. Randomized clinical trials are needed to
allow for the development of better agents, regimens and techniques to address
above mentioned issues and reduce morbidity and mortality among lung transplant
recipients.
PMID- 25132974
TI - Bridge to lung transplantation and rescue post-transplant: the expanding role of
extracorporeal membrane oxygenation.
AB - Over the last several decades, the growth of lung transplantation has been
hindered by a much higher demand for donor lungs than can be supplied, leading to
considerable waiting time and mortality among patients waiting for transplant.
This has led to the search for an alternative bridging strategy in patients with
end-stage lung disease. The use of extracorporeal membrane oxygenation (ECMO) as
a bridge to lung transplantation as well as a rescue strategy post-transplant for
primary graft dysfunction (PGD) has been studied previously, however due to
initially poor outcomes, its use was not heavily instituted. In recent years,
with significant improvement in technologies, several single and multi-center
studies have shown promising outcomes related to the use of ECMO as a bridging
strategy as well as a therapy for patients suffering from PGD post-transplant.
These results have challenged our current notion on ECMO use and hence forced us
to reexamine the utility, efficacy and safety of ECMO in conjunction with lung
transplantation. Through this review, we will address the various aspects related
to ECMO use as a bridge to lung transplantation as well as a rescue post
transplant in the treatment of PGD. We will emphasize newer technologies related
to ECMO use, examine recent observational studies and randomized trials of ECMO
use before and after lung transplantation, and reflect upon our own institutional
experience with the use of ECMO in these difficult clinical situations.
PMID- 25132977
TI - Heart transplantation.
AB - Heart failure remains a major global problem with approximately 6 million
individuals suffering from heart failure in the United States alone. The surgical
technique of heart transplantation, popularized by Dr. Norman Shumway, has led to
its success and currently remains the best treatment options for patients with
end-stage. However, with the continued limitation of donor organs and the rapid
development of ventricular assist device technology, the number of patients
bridged to transplant with mechanical circulatory support has increased
significantly. This has created some new technical challenges for heart
transplantation. Therefore, it is now important to be familiar with multiple new
technical challenges associated with the surgical techniques of heart
transplantation with an ultimate goal in reducing donor heart ischemic time,
recipient cardiopulmonary bypass time and post-operative complications. In this
review, we described our technique of heart transplantation including the timing
of the operation, recipient cardiectomy and donor heart implantation.
PMID- 25132976
TI - Donor selection in heart transplantation.
AB - There is increased scrutiny on the quality in health care with particular
emphasis on institutional heart transplant survival outcomes. An important aspect
of successful transplantation is appropriate donor selection. We review the
current guidelines as well as areas of controversy in the selection of
appropriate hearts as donor organs to ensure optimal outcomes. This decision is
paramount to the success of a transplant program as well as recipient survival
and graft function post-transplant.
PMID- 25132975
TI - Pediatric heart transplantation-indications and outcomes in the current era.
AB - Pediatric heart transplantation (HTx) remains an important treatment option in
the care of children with end-stage heart disease, whether it is secondary to
cardiomyopathy or congenital heart disease (CHD). As surgical outcomes for CHD
have improved, the indications for pediatric HTx have had to be dynamic, not only
for children with CHD but also for the growing population of adults with CHD. As
the field of pediatric HTx has evolved, the outcomes for children undergoing HTx
have improved. This is undoubtedly due to the continued research efforts of both
single-center studies, as well as research collaboratives such as the
International Society for Heart and Lung Transplantation (ISHLT) and the
Pediatric Heart Transplant Study (PHTS) group. Research collaboratives are
increasingly important in pediatric HTx as single center studies for a limited
patient population may not elicit strong enough evidence for practice evolution.
Similarly, complications that limit the long term graft survival may occur in a
minority of patients thus pooled experience is essential. This review focuses on
the indications and outcomes for pediatric HTx, with a special emphasis on
studies generated by these research collaboratives.
PMID- 25132978
TI - Left ventricular assist devices as a bridge to cardiac transplantation.
AB - Heart failure remains a significant cause of morbidity and mortality, affecting
over five million patients in the United States. Continuous-flow left ventricular
assist devices (LVAD) have become the standard of care for patients with end
stage heart failure. This review highlights the current state of LVAD as a bridge
to transplant (BTT) in patients requiring mechanical circulatory support (MCS).
PMID- 25132979
TI - Adult heart transplant: indications and outcomes.
AB - Cardiac transplantation is the treatment of choice for many patients with end
stage heart failure (HF) who remain symptomatic despite optimal medical therapy.
For carefully selected patients, heart transplantation offers markedly improved
survival and quality of life. Risk stratification of the large group of patients
with end-stage HF is essential for identifying patients who are most likely to
benefit, particularly as the number of suitable donors is insufficient to meet
demand. The indications for heart transplant and review components of the pre
transplant evaluation, including the role for exercise testing and risk scores
such as the Heart Failure Survival Score (HFSS) and Seattle Heart Failure Model
(SHFM) are summarized. Common contraindications are also discussed. Outcomes,
including survival and common complications such as coronary allograft
vasculopathy are reviewed.
PMID- 25132980
TI - Heart-lung transplantation: pediatric indications and outcomes.
AB - As indications for heart-lung transplant (HLT) have changed to some degree in the
past 30 years, this treatment is being used less frequently in children due to
more advanced care of severe heart and lung disease. This is fortunate as the
outcomes for HLT are poor compared to other solid organ transplants and this is
mainly due to the poorer outcome of the lung graft.
PMID- 25132981
TI - Heart-lung transplantation: adult indications and outcomes.
AB - Combined heart-lung transplantation remains the only definitive therapy for
patients who have both end-stage heart failure and end-stage lung failure. The
most common indication is congenital heart disease (CHD) and the proportion is
increasing for acquired heart disease concomitant with pulmonary hypertension
and/or intrinsic lung diseases. Previously, idiopathic pulmonary hypertension was
the most common indication. However, it has been shown that right ventricular
failure can be reversed after double lung transplantation. Therefore, patients
with idiopathic pulmonary arterial hypertension (IPAH) should not undergo
combined heart-lung transplantation unless left ventricular dysfunction co
exists. The ISHLT registry data shows survival after heart-lung transplantation
is improving, but still its survival rates are 71% at 3 months, 63% at 1 year,
44% at 5 years and 31% at 10 years. With appropriate patient selection and
surgical expertise, these outcomes should improve further.
PMID- 25132983
TI - Heart-lung transplantation.
AB - Heart-lung transplantation itself is not a particularly difficult operation
technically. It is the setting in which this procedure is performed which is
difficult. The three issues of importance in a successful outcome are appropriate
harvest of the heart-lung bloc from the donor, careful explant of the heart and
lungs of the recipient, and finally the implant of the heart-lung bloc into the
recipient. None of this requires extraordinary technical skill, but does require
careful coordination and planning as well as adhering to some fundamental
principles. One of the major pitfalls encountered is bleeding related to the
explant procedure. Another is graft failure related to harvest and/or the implant
procedure. The third is injury to either the phrenic nerve(s) or the left
recurrent laryngeal nerve related to the explant procedure. Heart-lung
transplantation is a major investment in resources of all sorts including
financial, personnel, as well as the organs themselves. It is absolutely
imperative that this procedure be performed only by experienced surgeons in
centers with established expertise.
PMID- 25132982
TI - Preservation solutions for cardiac and pulmonary donor grafts: a review of the
current literature.
AB - Hypothermic preservation of donor grafts is imperative to ameliorate ischemia
related cellular damage prior to organ transplantation. Numerous solutions are in
existence with widespread variability among transplant centers as to a consensus
regarding the optimal preservation solution. Here, we present a concise review of
pertinent preservation studies involving cardiac and pulmonary allografts in an
attempt to minimize the variability among institutions and potentially improve
graft and patient survival. A biochemical comparison of common preservation
solutions was undertaken with an emphasis on Euro Collins (EC), University of
Wisconsin (UW), histidine-tryptophan-ketoglutarate (HTK), Celsior (CEL), Perfadex
(PER), Papworth, and Plegisol. An appraisal of the literature ensued containing
the aforementioned preservation solutions in the setting of cardiac and pulmonary
transplantation. Available evidence supports UW solution as the preservation
solution of choice for cardiac transplants with encouraging outcomes relative to
notable contenders such as CEL. Despite its success in the setting of cardiac
transplantation, its use in pulmonary transplantation remains suboptimal and
improved outcomes may be seen with PER. Together, we suggest, based on the
literature that the use of UW solution and PER for cardiac and pulmonary
transplants, respectively may improve transplant outcomes such as graft and
patient survival.
PMID- 25132984
TI - Overview of paediatric heart-lung transplantation: a global perspective.
PMID- 25132985
TI - The Mitochondria-Targeted Antioxidant SkQ1 Downregulates Aryl Hydrocarbon
Receptor-Dependent Genes in the Retina of OXYS Rats with AMD-Like Retinopathy.
AB - The mitochondria-targeted antioxidant SkQ1 is a novel drug thought to retard
development of age-related diseases. It has been shown that SkQ1 reduces clinical
signs of retinopathy in senescence-accelerated OXYS rats, which are a known
animal model of human age-related macular degeneration (AMD). The aim of this
work was to test whether SkQ1 affects transcriptional activity of AhR (aryl
hydrocarbon receptor) and Nrf2 (nuclear factor erythroid 2-related factor 2),
which are considered as AMD-associated genes in the retina of OXYS and Wistar
rats. Our results showed that only AhR and AhR-dependent genes were sensitive to
SkQ1. Dietary supplementation with SkQ1 decreased the AhR mRNA level in both OXYS
and Wistar rats. At baseline, the retinal Cyp1a1 mRNA level was lower in OXYS
rats. SkQ1 supplementation decreased the Cyp1a1 mRNA level in Wistar rats, but
this level remained unchanged in OXYS rats. Baseline Cyp1a2 and Cyp1b1 mRNA
expression was stronger in OXYS than in Wistar rats. In the OXYS strain, Cyp1a2
and Cyp1b1 mRNA levels decreased as a result of SkQ1 supplementation. These data
suggest that the Cyp1a2 and Cyp1b1 enzymes are involved in the pathogenesis of
AMD-like retinopathy of OXYS rats and are possible therapeutic targets of SkQ1.
PMID- 25132987
TI - Subclinical Iodine Deficiency among Pregnant Women in Haramaya District, Eastern
Ethiopia: A Community-Based Study.
AB - Background. Iodine deficiency in pregnancy is a worldwide problem. This study
aimed to assess prevalence and predictors of subclinical iodine deficiency among
pregnant women in Haramaya district, eastern Ethiopia. Methods. A cross
sectional, community-based study was conducted on 435 pregnant women existing in
ten randomly selected rural kebeles (kebele is the smallest administrative unit
in Ethiopia). Data on the study subjects' background characteristics, dietary
habits, and gynecological/obstetric histories were collected via a structured
questionnaire. UIC of <150 MUg/L defined subclinical iodine deficiency. Data were
analyzed by Stata 11. A multivariable logistic regression was used to identify
the predictors of subclinical iodine deficiency. Results. The median urinary
iodine concentration (MUIC) was 58.1 MUg/L and 82.8% of the women who had
subclinical iodine deficiency. The risk of subclinical iodine deficiency was
reduced by the use of iodized salt (AOR = 0.13) and by intake of milk twice a
month or more (AOR = 0.50), but it was increased by maternal illiteracy (AOR =
3.52). Conclusion. Iodine nutritional status of the pregnant women was poor. This
shows that women and their children are exposed to iodine deficiency and its
adverse effects. Thus, they need urgent supplementation with iodine and improved
access to and intake of iodized salt and milk during pregnancy.
PMID- 25132988
TI - Lovastatin as an adjuvant to lithium for treating manic phase of bipolar
disorder: a 4-week, randomized, double-blind, placebo-controlled clinical trial.
AB - Objectives. Many patients with bipolar disorder suffer from metabolic disorder.
Lovastatin is effective for treating major depression. This double-blind
randomized placebo controlled clinical trial investigates whether lovastatin is a
useful adjuvant to lithium for treating mania. Methods. Fifty-four patients with
bipolar disorder-manic phase were randomly allocated into lovastatin or placebo
group. The clinical symptoms were assessed at baseline, week 2, and week 4 using
Young Mania Rating Scale. Adverse effects were checked. Results. Forty-six out of
54 patients completed this trial. The mania score in the lovastatin group
decreased from 40.6 (11.1) at baseline to 12.9 (8.7) and 4.1 (5.4) at weeks 2 and
4, respectively. The score in the placebo group decreased from 41.0 (11.2) at
baseline to 12.8 (8.07) and 5.8 (4.6) at weeks 2 and 4, respectively. However,
there was no significant difference between groups at week 2 and week 4. The
adverse effects rates were comparable between the two groups. No serious adverse
effect was found. Tremor and nausea were the most common adverse effects.
Conclusions. Lovastatin neither exacerbated nor decreased the symptoms of mania
in patients with bipolar disorder. Current results support that the combination
of lovastatin with lithium is tolerated well in bipolar disorder. The trial was
registered with the Iranian Clinical Trials Registry (IRCT201302203930N18).
PMID- 25132986
TI - Cardiometabolic risk assessments by body mass index z-score or waist-to-height
ratio in a multiethnic sample of sixth-graders.
AB - Convention defines pediatric adiposity by the body mass index z-score (BMIz)
referenced to normative growth charts. Waist-to-height ratio (WHtR) does not
depend on sex-and-age references. In the HEALTHY Study enrollment sample, we
compared BMIz with WHtR for ability to identify adverse cardiometabolic risk.
Among 5,482 sixth-grade students from 42 middle schools, we estimated explanatory
variations (R (2)) and standardized beta coefficients of BMIz or WHtR for
cardiometabolic risk factors: insulin resistance (HOMA-IR), lipids, blood
pressures, and glucose. For each risk outcome variable, we prepared adjusted
regression models for four subpopulations stratified by sex and high versus lower
fatness. For HOMA-IR, R (2) attributed to BMIz or WHtR was 19%-28% among high
fatness and 8%-13% among lower-fatness students. R (2) for lipid variables was 4%
9% among high-fatness and 2%-7% among lower-fatness students. In the lower
fatness subpopulations, the standardized coefficients for total cholesterol/HDL
cholesterol and triglycerides tended to be weaker for BMIz (0.13-0.20) than for
WHtR (0.17-0.28). Among high-fatness students, BMIz and WHtR correlated with
blood pressures for Hispanics and whites, but not black boys (systolic) or girls
(systolic and diastolic). In 11-12 year olds, assessments by WHtR can provide
cardiometabolic risk estimates similar to conventional BMIz without requiring
reference to a normative growth chart.
PMID- 25132989
TI - Validation of a new instrument for self-assessment of nurses' core competencies
in palliative care.
AB - Competence can be seen as a prerequisite for high quality nursing in clinical
settings. Few research studies have focused on nurses' core competencies in
clinical palliative care and few measurement tools have been developed to explore
these core competencies. The purpose of this study was to test and validate the
nurses' core competence in palliative care (NCPC) instrument. A total of 122
clinical nurse specialists who had completed a postbachelor program in palliative
care at two university colleges in Norway answered the questionnaire. The initial
analysis, with structural equation modelling, was run in Mplus 7. A modified
confirmatory factor analysis revealed the following five domains: knowledge in
symptom management, systematic use of the Edmonton symptom assessment system,
teamwork skills, interpersonal skills, and life closure skills. The actual
instrument needs to be tested in a practice setting with a larger sample to
confirm its usefulness. The instrument has the potential to be used to refine
clinical competence in palliative care and be used for the training and
evaluation of palliative care nurses.
PMID- 25132990
TI - Implementation intentions as a strategy to increase the notification rate of
potential ocular tissue donors by nurses: a clustered randomized trial in
hospital settings.
AB - Aim. The purpose of this study is to evaluate the impact, among nurses in
hospital settings, of a questionnaire-based implementation intentions
intervention on notification of potential ocular tissue donors to donation
stakeholders. Methods. This randomized intervention was clustered at the level of
hospital departments with two study arms: questionnaire-based implementation
intentions intervention and control. In the intervention group, nurses were asked
to plan specific actions if faced with a number of barriers when reporting
potential ocular donors. The primary outcome was the potential ocular tissue
donors' notification rate before and after the intervention. Analysis was based
on a generalized linear model with an identity link and a binomial distribution.
Results. We compared outcomes in 26 departments from 5 hospitals, 13 departments
per condition. The implementation intentions intervention did not significantly
increase the notification rate of ocular tissue donors (intervention: 23.1%
versus control: 21.1%; chi (2) = 1.14, 2; P = 0.56). Conclusion. A single and
brief implementation intentions intervention among nurses did not modify the
notification rate of potential ocular tissue donors to donation stakeholders. Low
exposure to the intervention was a major challenge in this study. Further studies
should carefully consider a multicomponent intervention to increase exposure to
this type of intervention.
PMID- 25132992
TI - Endovascular embolisation of visceral artery pseudoaneurysms.
AB - Objective. To evaluate the technical success, safety, and outcome of endovascular
embolization procedure in management of visceral artery pseudoaneurysms.
Materials and Methods. 46 patients were treated for 53 visceral pseudoaneurysms
at our institution. Preliminary diagnostic workup in all cases was performed by
contrast enhanced abdominal CT scan and/or duplex ultrasound. In all patients,
embolization was performed as per the standard departmental protocol. For data
collection, medical records and radiology reports of all patients were
retrospectively reviewed. Technical success, safety, and outcome of the procedure
were analyzed. Results. Out of 46 patients, 13 were females and 33 were males.
Mean patient age was 44.79 +/- 13.9 years and mean pseudoaneurysm size was 35 +/-
19.5 mm. Technical success rate for endovascular visceral pseudoaneurysm coiling
was 93.47% (n = 43). Complication rate was 6.52% (n = 3). Followup was done for a
mean duration of 21 +/- 1.6 months (0.5-69 months). Complete resolution of
symptoms or improvement in clinical condition was seen in 36 patients (80%) out
of those 45 in whom procedure was technically successful. Conclusion. Results of
embolization of visceral artery pseudoaneurysms with coils at our center showed
high success rate and good short term outcome.
PMID- 25132993
TI - Psychological Impacts among Older and Younger People Living with HIV/AIDS in
Nanning, China.
AB - Objectives. The HIV epidemic has drastically increased among older adults in
China, yet little research has examined the psychological impacts among older and
younger people living with HIV/AIDS (PLWHAs). This study examined and compared
self-efficacy, depression, well-being, and quality of life among older and
younger PLWHAs in China. Method. A two-stage sampling procedure was used to
recruit a final sample of 148 participants. Older adults were defined as age 50
and older. Result. Compared to younger PLWHAs aged 18-49 years old, older PLWHAs
reported lower levels of well-being (7.6 versus 11.4), higher levels of
depression (18.6 versus 15.8), and poorer quality of life. Self-efficacy was
similar among older (23.9) and younger (24.6) PLWHAs. A higher level of
depression among older PLWHAs was associated with much lower levels of subjective
well-being and quality of life (physical health and psychological health).
Conclusion. The findings suggest that older PLWHAs face psychological problems
and mental health challenges beyond those experienced by younger PLWHAs.
Intervention programs dedicated to improving mental health and quality of life
are greatly needed for HIV infected older adults.
PMID- 25132991
TI - The epidemiology of pulmonary nontuberculous mycobacteria: data from a general
hospital in Athens, Greece, 2007-2013.
AB - BACKGROUND: The epidemiology of pulmonary nontuberculous mycobacteria (NTM) in
Greece is largely unknown. OBJECTIVES: To determine the incidence and the
demographic, microbiological, and clinical characteristics of patients with
pulmonary NTM infection and pulmonary NTM disease. METHODS: A retrospective
review of the demographic, microbiological, and clinical characteristics of
patients with NTM culture-positive respiratory specimens from January 2007 to May
2013. RESULTS: A total of 120 patients were identified with at least one
respiratory NTM isolate and 56 patients (46%) fulfilled the microbiological
ATS/IDSA criteria for NTM disease. Of patients with adequate data, 16% fulfilled
the complete ATS/IDSA criteria for NTM disease. The incidence of pulmonary NTM
infection and disease was 18.9 and 8.8 per 100.000 inpatients and outpatients,
respectively. The spectrum of NTM species was high (13 species) and predominated
by M. avium-intracellulare complex (M. avium (13%), M. intracellulare (10%)), M.
gordonae (14%), and M. fortuitum (12%). The ratio of isolation of NTM to M.
tuberculosis in all hospitalized patients was 0.59. CONCLUSIONS: The first data
on the epidemiology of pulmonary NTM in Athens, Greece, are presented. NTM
infection is common in patients with chronic respiratory disease. However, only a
significantly smaller proportion of patients fulfill the criteria for NTM
disease.
PMID- 25132994
TI - Sound Lateralization Test Distinguishes Unimpaired MS Patients from Healthy
Controls.
AB - There is an urgent need to develop a practical and reliable clinical measure of
disease progression in early and mild MS. We hypothesized that a test of sound
lateralization, which is exquisitely sensitive to transmission delays in auditory
brainstem, could be more useful for detecting processing speed deficits in mildly
impaired MS subjects than standard cognitive tasks. Objective. To develop a
practical test of sound lateralization for the clinic and to compare performance
of MS subjects with variable disability and healthy subjects on Sound
Lateralization Test (SLT) and two speed-of-processing tasks. Design. 42 healthy
controls and 90 subjects with clinically definite MS, divided into no, mild, and
moderate disability strata, were administered the Symbol Digit Modalities Test
(SDMT), and 3-second Paced Auditory Serial Addition Test (PASAT). Results. All of
the tests showed an overall difference in performance between controls and the
three MS groups, but only the SLT measured a significant difference between
controls and the no disability group. Conclusion. SLT is rapidly applied,
technically simple, and superior to standard processing speed tests for
discriminating between healthy controls and nondisabled MS subjects. SLT should
be investigated as an outcome measure in early-phase trials and for monitoring
early disease progression in the clinic.
PMID- 25132995
TI - Similarity of fibroglandular breast tissue content measured from magnetic
resonance and mammographic images and by a mathematical algorithm.
AB - Women with high breast density (BD) have a 4- to 6-fold greater risk for breast
cancer than women with low BD. We found that BD can be easily computed from a
mathematical algorithm using routine mammographic imaging data or by a curve
fitting algorithm using fat and nonfat suppression magnetic resonance imaging
(MRI) data. These BD measures in a strictly defined group of premenopausal women
providing both mammographic and breast MRI images were predicted as well by the
same set of strong predictor variables as were measures from a published
laborious histogram segmentation method and a full field digital mammographic
unit in multivariate regression models. We also found that the number of
completed pregnancies, C-reactive protein, aspartate aminotransferase, and
progesterone were more strongly associated with amounts of glandular tissue than
adipose tissue, while fat body mass, alanine aminotransferase, and insulin like
growth factor-II appear to be more associated with the amount of breast adipose
tissue. Our results show that methods of breast imaging and modalities for
estimating the amount of glandular tissue have no effects on the strength of
these predictors of BD. Thus, the more convenient mathematical algorithm and the
safer MRI protocols may facilitate prospective measurements of BD.
PMID- 25132996
TI - Diagnosis of spontaneous bacterial peritonitis and an in situ hybridization
approach to detect an "unidentified" pathogen.
AB - Spontaneous bacterial peritonitis (SBP) is a frequent and severe complication in
cirrhotic patients with ascites. Although identifying the pathogen(s) plays a
major role in the management of infectious diseases, ascitic fluid cultures often
show negative results in patients with clinical signs and symptoms of SBP, and
ascitic fluid cell analyses are the gold standard method for diagnosing SBP. SBP
is generally diagnosed based on an increased number of polymorphonuclear
neutrophils in the ascitic fluid (>250/mm(3)), and the identification of the
causal pathogen may not be given consideration. We newly developed an in situ
hybridization (ISH) method to provide early and direct evidence of bacterial
infection in ascites in patients with SBP. This paper will review the diagnosis
of SBP, including our novel approach with ISH method to detect bacterial DNA in
SBP ascitic fluid.
PMID- 25132999
TI - Ectopic 3rd molar tooth in the maxillary antrum.
AB - Location of ectopic tooth in a nondentate area like the maxillary antrum is rare.
A 17-year-old boy, with one year history of recurrent right facial swelling and
radiographic finding of a maxillary third molar tooth located at the posterior
wall of the maxillary antrum, is presented. Under endotracheal intubation, the
tooth was extracted through a Caldwell-Luc antrostomy approach and patient had an
uneventful recovery and has been symptom free for eight months. Ectopic tooth in
the maxillary antrum is rare and is commonest with maxillary third molar. It may
be symptomless but is more commonly associated with inflammatory symptoms. The
treatment of choice is surgical excision which is mostly carried out with
Caldwell-Luc approach, even though endoscopic approach is being reported.
PMID- 25132998
TI - Cholangiocarcinoma with respect to IgG4 Reaction.
AB - IgG4 reactions marked by infiltration of IgG4-positive plasma cells in affected
organs occur in cancer patients and in patients with IgG4-related diseases.
Extrahepatic cholangiocarcinomas including gall bladder cancer are often
accompanied by significant IgG4 reactions; these reactions show a negative
correlation with CD8-positive cytotoxic T cells, suggesting that the evasion of
immune surveillance is associated with cytotoxic T cells. The regulatory cytokine
IL-10 may induce IgG4-positive plasma cell differentiation or promote B cell
switching to IgG4 in the presence of IL-4. Cholangiocarcinoma cells may function
as nonprofessional antigen presenting cells that indirectly induce IgG4 reactions
via the IL-10-producing cells and/or these may act as Foxp3-positive and IL-10
producing cells that directly induce IgG4 reactions. Moreover, IgG4-related
disease is a high-risk factor for cancer development; IgG4-related sclerosing
cholangitis (IgG4-SC) cases associated with cholangiocarcinoma or its precursor
lesion biliary intraepithelial neoplasia (BilIN) have been reported. IgG4
positive cell infiltration is an important finding of IgG4-SC but is not a
histological hallmark of IgG4-SC. For the diagnosis of IgG4-SC, its
differentiation from cholangiocarcinoma remains important.
PMID- 25133000
TI - Nonsurgical treatment of two periapical lesions with calcium hydroxide using two
different vehicles.
AB - Calcium hydroxide is used extensively as an intracanal medicament in endodontics
for many years. It is used in various clinical situations such as to promote
apexification, to repair perforation, to enhance healing of periapical lesions,
to control root resorption, and to control exudation in teeth with persistent
periapical inflammation. This paper presents a case report in which Ca(OH)2 was
used as an intracanal medicament for treatment of periradicular lesions using two
different vehicles in two different teeth of same patient.
PMID- 25132997
TI - Genetic diseases that predispose to early liver cirrhosis.
AB - Inherited liver diseases are a group of metabolic and genetic defects that
typically cause early chronic liver involvement. Most are due to a defect of an
enzyme/transport protein that alters a metabolic pathway and exerts a pathogenic
role mainly in the liver. The prevalence is variable, but most are rare
pathologies. We review the pathophysiology of such diseases and the diagnostic
contribution of laboratory tests, focusing on the role of molecular genetics. In
fact, thanks to recent advances in genetics, molecular analysis permits early and
specific diagnosis for most disorders and helps to reduce the invasive approach
of liver biopsy.
PMID- 25133001
TI - Cardiac failure as an unusual presentation in a patient with history of
amyotrophic lateral sclerosis.
AB - Amyotrophic lateral sclerosis (ALS) is the most well-known form of motor neuron
diseases in which both upper and lower motor neurons are involved in this
disease. We presented an unusual case of ALS whom had presented with chief
complaint of dyspnea. Cardiac failure was diagnosed at the final stage of the ALS
disease. The pathogenetic mechanism leading to an elevated occurrence of
cardiomyopathy in ALS is not comprehensible. Dilated cardiomyopathy has been
explained in some previous studies. Based on the collected data, it was
hypothesized that cardiomyopathy is underdiagnosed in the ALS population,
probably because symptoms are masqueraded as a result of the patients'
disability. It was suggested that in all motor neuron diseases a serial
cardiological evaluation should be executed, including annual echocardiography.
PMID- 25133002
TI - Carcinoma buccal mucosa underlying a giant cutaneous horn: a case report and
review of the literature.
AB - Cutaneous horn is a conical, dense, and hyperkeratotic protrusion that often
appears similar to the horn of an animal. Giant cutaneous horns are rare; no
incidence or prevalence has been reported. The significance of cutaneous horns is
that they occur in association with, or as a response to, a wide variety of
underlying benign, premalignant, and malignant cutaneous diseases. A case of
giant cutaneous horn of left oral commissure along with carcinoma left buccal
mucosa is reported here as an extremely rare oral/perioral pathology.
PMID- 25133004
TI - Primary renal angiosarcoma with extensive necrosis: a difficult diagnosis.
AB - Angiosarcoma of the kidney is an exceedingly rare and aggressive neoplasm. Very
few cases have been reported in the English literature to date. We report a case
of primary renal angiosarcoma with extensive necrosis and discuss its diagnostic
difficulties. An 86-year-old male presented with a 12 cm necrotic renal mass and
multiple pulmonary and hepatic nodules. A CT guided renal biopsy revealed
extensive necrosis and few vascular channels lined by malignant endothelial
cells. Diagnosis was given on a morphologic base and proven by an
immunohistochemical study. Primary renal angiosarcoma should be included among
the differential diagnosis of necrotic renal lesions.
PMID- 25133003
TI - Thyroid-like follicular carcinoma of the kidney in a young patient with history
of pediatric acute lymphoblastic leukemia.
AB - Thyroid-like follicular carcinoma of the kidney (TLFCK) is a rare histological
variant of renal cell carcinoma not currently included in the World Health
Organization classification of renal tumors. Only 24 previous cases of TLFCK have
been reported to date. We report a case of TLFCK in a 19-year-old woman with
history of pediatric acute lymphoblastic leukemia. This patient is the youngest
with TLFCK to be reported to date and the first with history of lymphoblastic
leukemia. The development of TLFCK in a young patient with history of
lymphoblastic leukemia is interesting and suggests that genes involved in
leukemogenesis may also be important for TLFCK pathogenesis. Recognition of TLFCK
is important to distinguish it from other conditions that show thyroid-like
features, as a misdiagnosis can result in adverse patient care.
PMID- 25133005
TI - Primary hairy cell leukemia/lymphoma of the breast: a case report and review of
the literature.
AB - Hairy cell leukemia/lymphoma (HCL) is a rare B-cell neoplasm primarily involving
spleen, bone marrow, and blood. However, other sites of primary involvement do
occur and can present a diagnostic and therapeutic challenge. We present an
unusual case of HCL involving predominantly the breast that was diagnosed as an
incidental finding during an elective reduction mammoplasty in an otherwise
healthy asymptomatic woman. Bone marrow performed for staging revealed limited
involvement by HCL. Notably, there was no splenomegaly and/or involvement of
other extramedullary sites. The peripheral blood revealed minimal involvement
detected by flow cytometry. Extensive immunohistochemical studies supported by
positive BRAF V600E mutational status confirmed the diagnosis of HCL. The patient
remains asymptomatic without treatment one year following the diagnosis. This is
the first case of a well-documented HCL presenting primarily in the breast in an
asymptomatic patient. We review the literature on extramedullary, extrasplenic
involvement by HCL and discuss the diagnostic challenges as well as the utility
of immunohistochemistry and molecular studies in the diagnosis of atypical
presentations of HCL.
PMID- 25133006
TI - MRI in diagnosis of a giant prostatic utricle.
AB - A prostatic utricle cyst is an epithelial lined diverticulum arising from the
prostatic urethra and usually asymptomatic when small. When enlarged, it may be
symptomatic and is typically accompanied by hypospadias. We present a case of a
markedly enlarged prostatic utricle in a neonate without hypospadias,
demonstrated on voiding cystourethrography (VCUG), ultrasound, and 1.5 Tesla MRI.
PMID- 25133007
TI - Digital vasculitis in a patient with rheumatoid arthritis responded well to
adalimumab.
AB - 42-year-old old female patient, followed up with diagnosis of rheumatoid
arthritis for 15 years, was admitted with necrotising ulcer of left hand 1st and
2nd fingertips and pain, swelling, limitation of movement, and morning stiffness
at bilateral wrist, and metacarpophalangeal and proximal interphalangeal joints.
Laboratory tests revealed elevated acute phase reactants. Radial and ulnar
arteries were clear in upper extremity Doppler ultrasound. The patient was
diagnosed as RA activation and digital ulcer and administered iloprost infusion
for five days and 1 mg/kg corticosteroid and 20 mg/week methotrexate (MTX). After
one month, a partial regression of clinical and laboratory findings was observed.
However, 6 months later, due to relapsed and increased complaints and findings,
adalimumab 40 mg was administered. Two months later, clinical and laboratory
findings apparently decreased.
PMID- 25133009
TI - Concomitant urothelial cancer and renal tuberculosis.
AB - We report a case of coexisting urothelial cancer and renal tuberculosis in the
same kidney. The patient is a 72-year-old female with a remote history of treated
pulmonary tuberculosis who presented with haematuria, initial investigation of
which elucidated no definitive cause. Almost 1 year later, a diagnosis of
metastatic urinary tract cancer was made. The patient received chemotherapy for
advanced collecting duct type renal cell carcinoma, based on histological
features of renal biopsy. Subsequent confirmatory immunostains however led to a
revised diagnosis of urothelial cancer, necessitating a change in chemotherapy
regimen. A diagnosis of ipsilateral renal tuberculosis was made based on TB-PCR
testing of renal biopsy tissue and anti-TB therapy was coadministered with
chemotherapy. The patient died 9 months after diagnosis of metastatic urothelial
cancer.
PMID- 25133008
TI - Achalasia Secondary to Submucosal Invasion by Poorly Differentiated
Adenocarcinoma of the Cardia, Siewert II: Consideration on Preoperative Workup.
AB - Secondary achalasia due to submucosal invasion of cardia by gastric cancer is a
rare condition. We report a case of pseudoachalasia, secondary to the involvement
of gastroesophageal junction by poorly differentiated gastric cancer, initially
mistaken as idiopathic form. We focus on the difficulty to establish differential
diagnosis only on the basis of routine exams and we stress the necessity of
"second level" instrumental exams; EUS in routine workup in selected patients
should be considered. We support that routine workup based on history, clinical
presentation, radiological and endoscopic findings, and certainly manometry could
be insufficient for a correct differential diagnosis between primary and
secondary forms in some patients.
PMID- 25133010
TI - Bridging endovascular therapy and subsequent surgical repair for the treatment of
infected aneurysms after percutaneous cardiac intervention.
AB - Bridging endovascular therapy, accompanied by a second stage open surgical repair
was used to treat a rare case of infected aneurysms alongside external iliac
artery after a percutaneous cardiac intervention. Because these aneurysms require
early treatment, we suggest this approach, in order to avoid immediate, major
surgery in a recently symptomatic cardiac and bacteremic patient receiving dual
antiplatelet therapy. The approach seems to be safe and durable.
PMID- 25133011
TI - Poststroke muscle architectural parameters of the tibialis anterior and the
potential implications for rehabilitation of foot drop.
AB - Poststroke dorsiflexor weakness and paretic limb foot drop increase the risk of
stumbling and falling and decrease overall functional mobility. It is of interest
whether dorsiflexor muscle weakness is primarily neurological in origin or
whether morphological differences also contribute to the impairment. Ten
poststroke hemiparetic individuals were imaged bilaterally using noninvasive
medical imaging techniques. Magnetic resonance imaging was used to identify
changes in tibialis anterior muscle volume and muscle belly length.
Ultrasonography was used to measure fascicle length and pennation angle in a
neutral position. We found no clinically meaningful bilateral differences in any
architectural parameter across all subjects, which indicates that these subjects
have the muscular capacity to dorsiflex their foot. Therefore, poststroke
dorsiflexor weakness is primarily neural in origin and likely due to muscle
activation failure or increased spasticity of the plantar flexors. The current
finding suggests that electrical stimulation methods or additional neuromuscular
retraining may be more beneficial than targeting muscle strength (i.e.,
increasing muscle mass).
PMID- 25133013
TI - Prevalence of bla NDM, bla PER, bla VEB, bla IMP, and bla VIM Genes among
Acinetobacter baumannii Isolated from Two Hospitals of Tehran, Iran.
AB - Background and Objectives. The aim of this study was to determine the frequency
of bla NDM, bla PER, bla VEB, bla IMP, and bla VIM type genes among A. baumannii
isolates from hospitalized patients in two hospitals in Tehran, Iran. Patients
and Methods. Antibiotic susceptibility tests were performed by Kirby-Bauer disc
diffusion and Broth microdilution methods. The frequency of MBL (metallo-beta
lactamase) and ESBL (extended-spectrum-beta-lactamase) producers was evaluated by
CDDT. The beta -lactamases genes were detected by PCR and sequencing methods.
Results. The resistance of A. baumannii isolates against tested antibiotics was
as follows: 103 (95.4%) to ceftazidime, 108 (100%) to cefotaxime, 105 (95.7%) to
cefepime, 99 (91.7%) to imipenem, 99 (91.7%) to meropenem, 87 (80.6%) to
amikacin, 105 (97.2%) to piperacillin, 100 (92.6%) to ciprofloxacin, 103 (95.4%)
to piperacillin/tazobactam, 44 (40.7%) to gentamicin, 106 (98.1%) to
ampicillin/sulbactam, 106 (98.1%) to co-trimoxazole, 87 (80.6%) to tetracycline,
and 1 (1.8%) to colistin. Using combined disk diffusion test, 91 (84.2%) and 86
(86.86%) were ESBL and MBL producers, respectively. The prevalence of bla PER-1,
bla VEB-1, bla IMP-1, and bla VIM-1 genes was 71 (78.03%), 36 (39.5%), 3 (3.48%),
and 15 (17.44%), respectively. Conclusions. The prevalence of ESBLs and MBLs
producing A. baumannii strains detected in this study is a major concern and
highlights the need of infection control measures.
PMID- 25133012
TI - Claw lesions causing clinical lameness in lactating holstein frisian crossbred
cows.
AB - The objective of this study was to identify claw lesions causing clinical
lameness in lactating Holstein Frisian (HF) crossbred cows in dairy cattle.
Seventy dairy farmers were interviewed at the monthly meetings of Progressive
Dairy Farmers Association of Ludhiana, Punjab, India. Ten dairy farms were
randomly selected as per probability proportional to size and a total of 450
lactating HF crossbred cows were taken into the study. All the lactating cows
were scored for locomotion and rear leg view index. Trimming was done in all the
clinically lame animals (animals with locomotion scores 2 and 3) and equal number
of animals selected randomly from those with locomotion scores 0 and 1. Various
claw lesions were evaluated in both the groups. There was a significant
relationship between locomotion score and rear leg view index to identify
lameness. Sole ulcers and white line fissures were the lesions responsible for
clinical lameness. Other lesions did not cause clinical lameness but increased
the asymmetry in lactating HF crossbred cows. Both locomotion score and rear leg
view index could be reliably used to identify clinical lameness in lactating
cattle.
PMID- 25133014
TI - Detection of circulating tumor cells.
AB - The increasing number of treatment options for patients with metastatic
carcinomas has created an accompanying need for methods to determine if the tumor
will be responsive to the intended therapy and to monitor its effectiveness.
Ideally, these methods would be noninvasive and provide quantitative real-time
analysis of tumor activity in a variety of carcinomas. Assessment of circulating
tumor cells shed into the blood during metastasis may satisfy this need. Here we
review the CellSearch technology used for the detection of circulating tumor
cells and discuss potential future directions for improvements.
PMID- 25133015
TI - Biofilms and Helicobacter pylori: Dissemination and persistence within the
environment and host.
AB - The presence of viable Helicobacter pylori (H. pylori) in the environment is
considered to contribute to the levels of H. pylori found in the human
population, which also aids to increase its genetic variability and its
environmental adaptability and persistence. H. pylori form biofilms both within
the in vitro and in vivo environment. This represents an important attribute that
assists the survival of this bacterium within environments that are both hostile
and adverse to proliferation. It is the aim of this paper to review the ability
of H. pylori to form biofilms in vivo and in vitro and to address the inherent
mechanisms considered to significantly enhance its persistence within the host
and in external environments. Furthermore, the dissemination of H. pylori in the
external environment and within the human body and its impact upon infection
control will be discussed.
PMID- 25133016
TI - Role of Toll-like receptors in Helicobacter pylori infection and immunity.
AB - The gram-negative bacterium Helicobacter pylori (H. pylori) infects the stomachs
of approximately half of the world's population. Although infection induces an
immune response that contributes to chronic gastric inflammation, the response is
not sufficient to eliminate the bacterium. H. pylori infection causes peptic
ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Disease
outcome is linked to the severity of the host inflammatory response. Gastric
epithelial cells represent the first line of innate immune defence against H.
pylori, and respond to infection by initiating numerous cell signalling cascades,
resulting in cytokine induction and the subsequent recruitment of inflammatory
cells to the gastric mucosa. Pathogen recognition receptors of the Toll-like
receptor (TLR) family mediate many of these cell signalling events. This review
discusses recent findings on the role of various TLRs in the recognition of H.
pylori in distinct cell types, describes the TLRs responsible for the recognition
of individual H. pylori components and outlines the influence of innate immune
activation on the subsequent development of the adaptive immune response. The
mechanistic identification of host mediators of H. pylori-induced pathogenesis
has the potential to reveal drug targets and opportunities for therapeutic
intervention or prevention of H. pylori-associated disease by means of vaccines
or immunomodulatory therapy.
PMID- 25133017
TI - Molecular mechanisms of alcohol associated pancreatitis.
AB - Alcohol abuse is commonly associated with the development of both acute and
chronic pancreatitis. Despite this close association, the fact that only a small
percentage of human beings who abuse alcohol develop pancreatitis indicates that
alcohol abuse alone is not sufficient to initiate clinical pancreatitis. This
contention is further supported by the fact that administration of ethanol to
experimental animals does not cause pancreatitis. Because of these findings, it
is widely believed that ethanol sensitizes the pancreas to injury and additional
factors trigger the development of overt pancreatitis. How ethanol sensitizes the
pancreas to pancreatitis is not entirely known. Numerous studies have
demonstrated that ethanol and its metabolites have a number of deleterious
effects on acinar cells. Important acinar cells properties that are affected by
ethanol include: calcium signaling, secretion of zymogens, autophagy, cellular
regeneration, the unfolded protein response, and mitochondrial membrane
integrity. In addition to the actions of ethanol on acinar cells, it is apparent
that ethanol also affects pancreatic stellate cells. Pancreatic stellate cells
have a critical role in normal tissue repair and the pathologic fibrotic
response. Given that ethanol and its metabolites affect so many pancreatic
functions, and that all of these effects occur simultaneously, it is likely that
none of these effects is "THE" effect. Instead, it is most likely that the
cumulative effect of ethanol on the pancreas predisposes the organ to
pancreatitis. The focus of this article is to highlight some of the important
mechanisms by which ethanol alters pancreatic functions and may predispose the
pancreas to disease.
PMID- 25133018
TI - Early phase of acute pancreatitis: Assessment and management.
AB - Acute pancreatitis (AP) is a potentially life-threatening disease with a wide
spectrum of severity. The overall mortality of AP is approximately 5%. According
to the revised Atlanta classification system, AP can be classified as mild,
moderate, or severe. Severe AP often takes a clinical course with two phases, an
early and a late phase, which should both be considered separately. In this
review article, we first discuss general aspects of AP, including incidence,
pathophysiology, etiology, and grading of severity, then focus on the assessment
of patients with suspected AP, including diagnosis and risk stratification,
followed by the management of AP during the early phase, with special emphasis on
fluid therapy, pain management, nutrition, and antibiotic prophylaxis.
PMID- 25133019
TI - Potential role of NADPH oxidase in pathogenesis of pancreatitis.
AB - Studies have demonstrated that reactive oxygen species (ROS) are closely related
to inflammatory disorders. Nicotinamide adenine dinucleotide phosphate oxidase
(NOX), originally found in phagocytes, is the main source of ROS in nonphagocytic
cells. Besides directly producing the detrimental highly reactive ROS to act on
biomolecules (lipids, proteins, and nucleic acids), NOX can also activate
multiple signal transduction pathways, which regulate cell growth, proliferation,
differentiation and apoptosis by producing ROS. Recently, research on pancreatic
NOX is no longer limited to inflammatory cells, but extends to the aspect of
pancreatic acinar cells and pancreatic stellate cells, which are considered to be
potentially associated with pancreatitis. In this review, we summarize the
literature on NOX protein structure, activation, function and its role in the
pathogenesis of pancreatitis.
PMID- 25133020
TI - Barrett's oesophagus: Evidence from the current meta-analyses.
AB - Guidelines have been published regarding the management of Barrett's oesophagus
(columnar-lined oesophagus). These have examined the role of surveillance in an
effort to detect dysplasia and early cancer. The guidelines have provided
criteria for enrolment into surveillance and some risk stratification with regard
to surveillance interval. The research basis for the decisions reached with
regard to cancer risk is weak and this manuscript has examined the available data
published from meta-analyses up to 25(th) April 2013 (much of which has been
published since the guidelines and their most recent updates have been written).
There were 9 meta-analyses comparing patients with Barrett's oesophagus to
control populations. These have demonstrated that Barrett's oesophagus is more
common in males than females, in subjects who have ever smoked, in subjects with
obesity, in subjects with prolonged symptoms of gastro-oesophageal reflux
disease, in subjects who do not have infection with Helicobacter pylori and in
subjects with hiatus hernia. These findings should inform public health measures
in reducing the risk of Barrett's oesophagus and subsequent surveillance burden
and cancer risk. There were 8 meta-analyses comparing different groups of
patients with Barrett's oesophagus with regard to cancer risk. These have
demonstrated that there was no statistically significant benefit of antireflux
surgery over medical therapy, that endoscopic ablative therapy was effective in
reducing cancer risk that there was similar cancer risk in patients with
Barrett's oesophagus independent of geographic origin, that the adenocarcinoma
incidence in males is twice the rate in females, that the cancer risk in long
segment disease showed a trend to be higher than in short segment disease, that
there was a trend for higher cancer risk in low-grade dysplasia over non
dysplastic Barrett's oesophagus, that there is a lower risk in patients with
Helicobacter pylori infection and that there is a significant protective effect
of aspirin and statins. There were no meta-analyses examining the role of
intestinal metaplasia. These results demonstrate that guidance regarding
surveillance based on the presence of intestinal metaplasia, segment length and
the presence of low-grade dysplasia has a weak basis, and further consideration
should be given to gender and helicobacter status, ablation of the metaplastic
segment as well as the chemoprotective role of aspirin and statins.
PMID- 25133021
TI - Review to better understand the macroscopic subtypes and histogenesis of
intrahepatic cholangiocarcinoma.
AB - Intrahepatic cholangiocarcinoma is macroscopically classified into three
subtypes, mass-forming-type, periductal infiltrating-type, and intraductal growth
type. Each subtype should be preoperatively differentiated to perform the valid
surgical resection. Recent researches have revealed the clinical, radiologic,
pathobiological characteristics of each subtype. We reviewed recently published
studies covering various aspects of intrahepatic cholangiocarcinoma (ICC),
focusing especially on the macroscopic subtypes and stem cell features to better
understand the pathophysiology of ICC and to establish the valid therapeutic
strategy.
PMID- 25133022
TI - Laparoscopic surgery in the management of Crohn's disease.
AB - Crohn's disease is a chronic inflammatory bowel disease with surgery still
frequently necessary in its treatment. Since the 1990's, laparoscopic surgery has
become increasingly common for primary resections in patients with Crohn's
disease and has now become the standard of care. Studies have shown no difference
in recurrence rates when compared to open surgery and benefits include shorter
hospital stay, lower rates of wound infection and decreased time to bowel
function. This review highlights studies comparing the laparoscopic approach to
the open approach in specific situations, including cases of complicated Crohn's
disease.
PMID- 25133023
TI - Pathophysiology of fistula formation in Crohn's disease.
AB - Fistulae represent an important complication in patient suffering from Crohn's
disease (CD). Cumulative incidence of fistula formation in CD patients is 17%-50%
and about one third of patients suffer from recurring fistulae formation. Medical
treatment options often fail and also surgery frequently is not successful.
Available data indicate that CD-associated fistulae originate from an epithelial
defect that may be caused by ongoing inflammation. Having undergone epithelial to
mesenchymal transition (EMT), intestinal epithelial cells (IEC) penetrate into
deeper layers of the mucosa and the gut wall causing localized tissue damage
formation of a tube like structure and finally a connection to other organs or
the body surface. EMT of IEC may be initially aimed to improve wound repair
mechanisms since "conventional" wound healing mechanisms, such as migration of
fibroblasts, are impaired in CD patients. EMT also enhances activation of matrix
remodelling enzymes such as matrix metalloproteinase (MMP)-3 and MMP-9 causing
further tissue damage and inflammation. Finally, soluble mediators like TNF and
interleukin-13 further induce their own expression in an autocrine manner and
enhance expression of molecules associated with cell invasiveness aggravating the
process. Additionally, pathogen-associated molecular patterns also seem to play a
role for induction of EMT and fistula development. Though current knowledge
suggests a number of therapeutic options, new and more effective therapeutic
approaches are urgently needed for patients suffering from CD-associated
fistulae. A better understanding of the pathophysiology of fistula formation,
however, is a prerequisite for the development of more efficacious medical anti
fistula treatments.
PMID- 25133024
TI - Escherichia coli in chronic inflammatory bowel diseases: An update on adherent
invasive Escherichia coli pathogenicity.
AB - Escherichia coli (E. coli), and particularly the adherent invasive E. coli (AIEC)
pathotype, has been increasingly implicated in the ethiopathogenesis of Crohn's
disease (CD). E. coli strains with similar pathogenic features to AIEC have been
associated with other intestinal disorders such as ulcerative colitis, colorectal
cancer, and coeliac disease, but AIEC prevalence in these diseases remains
largely unexplored. Since AIEC was described one decade ago, substantial progress
has been made in deciphering its mechanisms of pathogenicity. However, the
molecular bases that characterize the phenotypic properties of this pathotype are
still not well resolved. A review of studies focused on E. coli populations in
inflammatory bowel disease (IBD) is presented here and we discuss about the
putative role of this species on each IBD subtype. Given the relevance of AIEC in
CD pathogenesis, we present the latest research findings concerning AIEC host
microbe interactions and pathogenicity. We also review the existing data
regarding the prevalence and abundance of AIEC in CD and its association with
other intestinal diseases from humans and animals, in order to discuss the AIEC
disease- and host-specificity. Finally, we highlight the fact that dietary
components frequently found in industrialized countries may enhance AIEC
colonization in the gut, which merits further investigation and the
implementation of preventative measures.
PMID- 25133025
TI - Similarities and differences between Behcet's disease and Crohn's disease.
AB - Behcet's disease (BD) is a chronic inflammatory condition with multisystem
involvement. Approximately 10%-15% of patients present with gastrointestinal
involvement. Involved sites and the endoscopic view usually resemble Crohn's
disease (CD). In addition to intestinal involvement, oral mucosa, the eyes, skin,
and joints are commonly affected. No pathognomonic laboratory test is available
for the diagnosis of either disease. Management approaches are also similar in
various aspects. Differentiating BD from CD is highly challenging. In this
article, the similarities and differences between BD and CD in terms of
epidemiology, etiopathogenesis, clinical and imaging findings, and
histopathological and therapeutic approaches are reviewed.
PMID- 25133027
TI - Pancreatitis-imaging approach.
AB - Pancreatitis is defined as the inflammation of the pancreas and considered the
most common pancreatic disease in children and adults. Imaging plays a
significant role in the diagnosis, severity assessment, recognition of
complications and guiding therapeutic interventions. In the setting of
pancreatitis, wider availability and good image quality make multi-detector
contrast-enhanced computed tomography (MD-CECT) the most used imaging technique.
However, magnetic resonance imaging (MRI) offers diagnostic capabilities similar
to those of CT, with additional intrinsic advantages including lack of ionizing
radiation and exquisite soft tissue characterization. This article reviews the
proposed definitions of revised Atlanta classification for acute pancreatitis,
illustrates a wide range of morphologic pancreatic parenchymal and associated
peripancreatic changes for different types of acute pancreatitis. It also
describes the spectrum of early and late chronic pancreatitis imaging findings
and illustrates some of the less common types of chronic pancreatitis, with
special emphasis on the role of CT and MRI.
PMID- 25133026
TI - Multidisciplinary and evidence-based management of fistulizing perianal Crohn's
disease.
AB - Perianal symptoms are common in patients with Crohn's disease and cause
considerable morbidity. The etiology of these symptoms include skin tags, ulcers,
fissures, abscesses, fistulas or stenoses. Fistula is the most common perianal
manifestation. Multiple treatment options exist although very few are evidence
based. The phases of treatment include: drainage of infection, assessment of
Crohn's disease status and fistula tracts, medical therapy, and selective
operative management. The impact of biological therapy on perianal Crohn's
disease is uncertain given that outcomes are conflicting. Operative treatment to
eradicate the fistula tract can be attempted once infection has resolved and
Crohn's disease activity is controlled. The operative approach should be tailored
according to the anatomy of the fistula tract. Definitive treatment is
challenging with medical and operative treatment rarely leading to true healing
with frequent complications and recurrence. Treatment success must be weighed
against the risk of complications, specially anal sphincter injury. A full
understanding of the etiology and all potential therapeutic options is critical
for success. Multidisciplinary management of fistulizing perianal Crohn's disease
is crucial to improve outcomes.
PMID- 25133029
TI - Role of hemostatic powders in the endoscopic management of gastrointestinal
bleeding.
AB - Acute gastrointestinal bleeding (AGIB) is a prevalent condition with significant
influence on healthcare costs. Endoscopy is essential for the management of AGIB
with a pivotal role in diagnosis, risk stratification and management. Recently,
hemostatic powders have been added to our endoscopic armamentarium to treat
gastrointestinal (GI) bleeding. These substances are intended to control active
bleeding by delivering a powdered product over the bleeding site that forms a
solid matrix with a tamponade function. Local activation of platelet aggregation
and coagulation cascade may be also boosted. There are currently three powders
commercially available: hemostatic agent TC-325 (Hemospray((r))), EndoClotTM
polysaccharide hemostatic system, and Ankaferd Bloodstopper((r)). Although the
available evidence is based on short series of cases and there is no randomized
controlled trial yet, these powders seem to be effective in controlling GI
bleeding from a variety of origins with a very favorable side effects profile.
They can be used either as a primary therapy or a second-line treatment, and they
seem to be especially indicated in cases of cancer-related bleeding and lesions
with difficult access. In this review, we will comment on the mechanism of
action, efficacy, safety and technical challenges of the use of powders in
several clinical scenarios and we will try to define the main current indications
of use and propose new lines of research in this area.
PMID- 25133028
TI - New insights to occult gastrointestinal bleeding: From pathophysiology to
therapeutics.
AB - Obscure gastrointestinal bleeding is still a clinical challenge for
gastroenterologists. The recent development of novel technologies for the
diagnosis and treatment of different bleeding causes has allowed a better
management of patients, but it also determines the need of a deeper comprehension
of pathophysiology and the analysis of local expertise in order to develop a
rational management algorithm. Obscure gastrointestinal bleeding can be divided
in occult, when a positive occult blood fecal test is the main manifestation, and
overt, when external sings of bleeding are visible. In this paper we are going to
focus on overt gastrointestinal bleeding, describing the physiopathology of the
most usual causes, analyzing the diagnostic procedures available, from the most
classical to the novel ones, and establishing a standard algorithm which can be
adapted depending on the local expertise or availability. Finally, we will review
the main therapeutic options for this complex and not so uncommon clinical
problem.
PMID- 25133030
TI - Predictors of response to anti-tumor necrosis factor therapy in ulcerative
colitis.
AB - Ulcerative colitis (UC) is an immune-mediated, chronic inflammatory disease of
the large intestine. Its course is characterized by flares of acute inflammation
and periods of low-grade chronic inflammatory activity or remission. Monoclonal
antibodies against tumor necrosis factor (anti-TNF) are part of the therapeutic
armamentarium and are used in cases of moderate to severe UC that is refractory
to conventional treatment with corticosteroids and/or immunosuppressants.
Therapeutic response to these agents is not uniform and a large percentage of
patients either fail to improve (primary non-response) or lose response after a
period of improvement (secondary non-response/loss of response). In addition, the
use of anti-TNF agents has been related to uncommon but potentially serious
adverse effects that preclude their administration or lead to their
discontinuation. Finally, use of these medications is associated with a
considerable cost for the health system. The identification of parameters that
may predict response to anti-TNF drugs in UC would help to better select for
patients with a high probability to respond and minimize risk and costs for those
who will not respond. Analysis of the major clinical trials and the accumulated
experience with the use of anti-TNF drugs in UC has resulted to the report of
such prognostic factors. Included are clinical and epidemiological
characteristics, laboratory markers, endoscopic indicators and molecular
(immunological/genetic) signatures. Such predictive parameters of long-term
outcomes may either be present at the commencement of treatment or determined
during the early period of therapy. Validation of these prognostic markers in
large cohorts of patients with variable characteristics will facilitate their
introduction into clinical practice and the best selection of UC patients who
will benefit from anti-TNF therapy.
PMID- 25133032
TI - Current status of predictive biomarkers for neoadjuvant therapy in esophageal
cancer.
AB - Neoadjuvant therapy has been proven to be extremely valuable and is widely used
for advanced esophageal cancer. However, a significant proportion of treated
patients (60%-70%) does not respond well to neoadjuvant treatments and develop
severe adverse effects. Therefore, predictive markers for individualization of
multimodality treatments are urgently needed in esophageal cancer. Recently,
molecular biomarkers that predict the response to neoadjuvant therapy have been
explored in multimodal approaches in esophageal cancer and successful examples of
biomarker identification have been reported. In this review, promising candidates
for predictive molecular biomarkers developed by using multiple molecular
approaches are reviewed. Moreover, treatment strategies based on the status of
predicted biomarkers are discussed, while considering the international
differences in the clinical background. However, in the absence of adequate
treatment options related to the results of the biomarker test, the usefulness of
these diagnostic tools is limited and new effective therapies for biomarker
identified nonresponders to cancer treatment should be concurrent with the
progress of predictive technologies. Further improvement in the prognosis of
esophageal cancer patients can be achieved through the introduction of novel
therapeutic approaches in clinical practice.
PMID- 25133033
TI - Epidemiological studies of esophageal cancer in the era of genome-wide
association studies.
AB - Esophageal cancer (EC) caused about 395000 deaths in 2010. China has the most
cases of EC and EC is the fourth leading cause of cancer death in China.
Esophageal squamous cell carcinoma (ESCC) is the predominant histologic type (90%
95%), while the incidence of esophageal adenocarcinoma (EAC) remains extremely
low in China. Traditional epidemiological studies have revealed that
environmental carcinogens are risk factors for EC. Molecular epidemiological
studies revealed that susceptibility to EC is influenced by both environmental
and genetic risk factors. Of all the risk factors for EC, some are associated
with the risk of ESCC and others with the risk of EAC. However, the details and
mechanisms of risk factors involved in the process for EC are unclear. The
advanced methods and techniques used in human genome studies bring a great
opportunity for researchers to explore and identify the details of those risk
factors or susceptibility genes involved in the process of EC. Human genome
epidemiology is a new branch of epidemiology, which leads the epidemiology study
from the molecular epidemiology era to the era of genome wide association studies
(GWAS). Here we review the epidemiological studies of EC (especially ESCC) in the
era of GWAS, and provide an overview of the general risk factors and those
genomic variants (genes, SNPs, miRNAs, proteins) involved in the process of ESCC.
PMID- 25133031
TI - Genetic update on inflammatory factors in ulcerative colitis: Review of the
current literature.
AB - Ulcerative colitis (UC) is one of the main types of inflammatory bowel disease,
which is caused by dysregulated immune responses in genetically predisposed
individuals. Several genetic factors, including interleukin and interleukin
receptor gene polymorphisms and other inflammation-related genes play central
role in mediating and modulating the inflammation in the human body, thereby
these can be the main cause of development of the disease. It is clear these data
are very important for understanding the base of the disease, especially in terms
of clinical utility and validity, but summarized literature is exiguous for
challenge health specialist that can used in the clinical practice nowadays. This
review summarizes the current literature on inflammation-related genetic
polymorphisms which are associated with UC. We performed an electronic search of
Pubmed Database among publications of the last 10 years, using the following
medical subject heading terms: UC, ulcerative colitis, inflammation, genes,
polymorphisms, and susceptibility.
PMID- 25133035
TI - Helicobacter pylori as a risk factor for central serous chorioretinopathy:
Literature review.
AB - Helicobacter pylori (H. pylori), a Gram-negative bacterium, is one of the most
frequent causes of gastrointestinal infections worldwide. It has been associated
as a pathogen for the human body with many systemic diseases, including different
eye diseases. We will focus on a specific eye disease called idiopathic central
serous chorioretinopathy (ICSCR). This disease is characterized by a serous
detachment of the neurosensory retina in the macular region, which affects the
vision to different degrees. Currently, the pathophysiology of ICSCR is not clear
and there is no effective treatment. However, several potential risk factors have
been elucidated. One of the factors that has more frequently been associated with
ICSCR is stress. As H. pylori was identified as a possible etiological factor for
occlusive arterial diseases in young people who were particularly stressed, it
was thought that H. pylori might also be present in ICSCR. Therefore, some
physicians started to test its presence in patents with ICSCR. If H. pylori
happened to be associated with ICSCR, the treatment of gastrointestinal infection
could also improve visual symptoms and help to remediate this eye disease.
Although H. pylori is highly prevalent in the general population, a true
correlation seems to exist. We present a review on the relationship between ICSCR
and H. pylori.
PMID- 25133034
TI - Perihilar cholangiocarcinoma: Current therapy.
AB - Perihilar cholangiocarcinoma, which is a rare primary malignancy, originates from
the epithelial cells of the bile duct. Usually invading the periductal tissues
and the lymph nodes, perihilar cholangiocarcinoma is commonly diagnosed in the
advanced stage of the disease and has a dismal prognosis. Currently, complete
hepatectomy is the primary therapy for curing this disease. Perioperative
assessment and available surgical procedures can be considered for achieving a
negative margin resection, which is associated with long-term survival and better
quality of life. For patients with unresectable cholangiocarcinoma, several
palliative treatments have been demonstrated to produce a better outcome; and
liver transplantation for selected patients with perihilar cholangiocarcinoma is
promising and desirable. However, the role of palliative treatments and liver
transplantation was controversial and requires more evidence and substantial
validity from multiple institutions. In this article, we summarize the data from
multiple institutions and discuss the resectability, mortality, morbidity and
outcome with different approaches.
PMID- 25133036
TI - Risk of cardiovascular disease in inflammatory bowel disease.
AB - Abundant scientific evidence supporting an association between inflammatory bowel
disease (IBD) and venous thromboembolic events, caused by an IBD related
hypercoagulability, is acknowledged and thromboprophylactic treatment strategies
are now implemented in the management of IBD patients. In contrary, the risk of
arterial thromboembolic disease, as ischemic heart disease, cerebrovascular
events, and mesenteric ischemia in patients with IBD remains uncertain and the
magnitude of a potentially increased risk is continuously debated, with ambiguous
risk estimates among studies. The evident role of inflammation in the
pathogenesis of atherosclerosis forms the basis of a biological plausible link;
the chronic systemic inflammation in IBD patients increases the risk of
atherosclerosis and thereby the risk of thrombotic events. Further, studies have
shown that the burden of traditional risk factors for atherosclerosis, such as
obesity, diabetes mellitus, and dyslipidemia is lower in IBD populations, thus
further strengthen the role of non-traditional risk factors, as chronic
inflammation in the linking of the two disease entities. Likewise, mortality from
cardiovascular disease in IBD remains questioned. The aim of the current review
is to give an up-date on the existing evidence of the possible association
between IBD and cardiovascular disease and to discuss traditional and non
traditional risk factors.
PMID- 25133037
TI - Cancer stem cells in Helicobacter pylori infection and aging: Implications for
gastric carcinogenesis.
AB - AIM: To demonstrated the combined effects of aging and carcinogen treatment on
cancer stem/stem-like cells (CSCs) of gastric mucosa in an animal model. METHODS:
In this study we investigated the effects of aging and Helicobacter pylori (H.
pylori) inflammation as a model for inflammation induced carcinogenesis in human
and rat gastric mucosa samples. In aging studies, we compared 4-mo old (young)
with 22 mo (aged) old Fischer-344 rats. For human studies, gastric biopsies and
resection specimens representing normal mucosa or different stages of H. pylori
gastritis and gastric adenocarcinomas were used for determining the expression of
stem cell markers CD166, ALDH1 and LGR5. In addition we performed
immunofluorescent double labeling for B-catenin and Lgr5 in both rat and human
gastric tissues to examine the status of Wnt signaling in these cells. RESULTS:
CSC markers ALDH1, LGR5, and CD166 were expressed in very low levels in normal
human gastric mucosa or young rat gastric mucosa. In contrast, level of
expression for all three markers significantly increased in H. pylori gastritis
and gastric adenocarcinomas as well as in normal gastric mucosa in aged rats. We
also observed cytoplasmic B-catenin staining in both aged rat and human H. pylori
inflamed gastric mucosa, which were found to be colocalized with Lgr5
immunoreactive cells. The increased number of ALDH1, CD166 and LGR5 positive
cells in H. pylori gastritis indicates that increased number of stem-like cells
in gastric mucosa is an early event, and may constitute an important step in the
progression to neoplasia. CONCLUSION: Our observation of the age-related increase
in cancer stem/stem-like cells in the gastric mucosa may explain the increased
incidence of gastric cancer during aging. Combination of aging and H. pylori
infection may have additive effects in progression to neoplasia.
PMID- 25133038
TI - Oxidative and nitrosative stress enzymes in relation to nitrotyrosine in
Helicobacter pylori-infected humans.
AB - AIM: To compare a possible relation between Helicobacter pylori (H. pylori) and
the oxygen- and nitrogen radical system in humans. METHODS: Mechanisms for H.
pylori to interfere with the oxygen and nitrogen radical system is of great
importance for understanding of the H. pylori persistence and pathogenesis.
Biopsies were obtained from the gastric wall of 21 individuals. Ongoing infection
with H. pylori was detected using direct analyze from the biopsies using
campylobacter-like organism test (CLO-test) and/or by using (14)C-urea breath
test. The individuals were divided in a negative H. pylori and a positive H.
pylori group. Expression in the gastric mucosa of inducible nitric oxide syntase
(iNOS), nicotinamide adenine dinucleotide phosphate-oxidase (NADPH-oxidase)
myeloperoxidase (MPO), and nitrotyrosine were assessed by Western blotting.
RESULTS: The individuals who undervent gastroscopy were divided in a H. pylori
neg. [n = 13, m/f = 7/6, age (mean) = 39] and a H. pylori pos. group [n= 8, m/f =
5/3, age (mean) = 53]. Using western blot analysis iNOS was detected as a 130 kDa
band. The iNOS expression was upregulated in the antrum of H. pylori infected
individuals in comparison to the controls, mean +/- SD being 12.6 +/- 2.4 vs 8.3
+/- 3.1, P < 0.01. There was a markedly upregulated expression of MPO in the
antrum of H. pylori infected individuals in comparison to the control group
without infection. In several of non-infected controls it was not possible to
detect any MPO expression at all, whereas the expression was high in all the
infected subjects, mean +/- SD being 5.1 +/- 3.4 vs 2.1 +/- 1.9, P < 0.05. The
NADPH-oxidase expression was analysed by detecting the NADPH-oxidase subunit p47
phox expression. P47-phox was detected as a 47 kDa band using Western blot, and
showed a significantly higher expression of p47-phox in the antrum of the H.
pylori infected individuals compared to the controls, mean +/- SD being 3.1 +/-
2.2 vs 0.3 +/- 0.2, P < 0.01. Regarding nitrotyrosine formation, Western blot did
not show any significant increase or decrease compared to controls, 7.0 +/- 0.9
vs 6.9 +/- 1.1, not significant. CONCLUSION: iNOS, MPO and NADPH-oxidase was up
regulated among H. pylori infected. Regarding nitrotyrosine no difference was
found. This support an H. pylori related inhibition of radical formation.
PMID- 25133039
TI - Diagnosis and treatment of gastroesophageal reflux disease.
AB - Gastroesophageal reflux disease (GERD) is a common disease with a prevalence as
high as 10%-20% in the western world. The disease can manifest in various
symptoms which can be grouped into typical, atypical and extra-esophageal
symptoms. Those with the highest specificity for GERD are acid regurgitation and
heartburn. In the absence of alarm symptoms, these symptoms can allow one to make
a presumptive diagnosis and initiate empiric therapy. In certain situations,
further diagnostic testing is needed to confirm the diagnosis as well as to
assess for complications or alternate causes for the symptoms. GERD complications
include erosive esophagitis, peptic stricture, Barrett's esophagus, esophageal
adenocarcinoma and pulmonary disease. Management of GERD may involve lifestyle
modification, medical therapy and surgical therapy. Lifestyle modifications
including weight loss and/or head of bed elevation have been shown to improve
esophageal pH and/or GERD symptoms. Medical therapy involves acid suppression
which can be achieved with antacids, histamine-receptor antagonists or proton
pump inhibitors. Whereas most patients can be effectively managed with medical
therapy, others may go on to require anti-reflux surgery after undergoing a
proper pre-operative evaluation. The purpose of this review is to discuss the
current approach to the diagnosis and treatment of gastroesophageal reflux
disease.
PMID- 25133040
TI - Use of methotrexate in inflammatory bowel disease in 2014: A User's Guide.
AB - Methotrexate has been used an immunomodulator in many autoimmune diseases,
including inflammatory bowel disease. However, many physicians are unfamiliar or
uncomfortable with its use in the management of inflammatory bowel disease. We
summarize the data for use of methotrexate in common clinical scenarios: (1)
steroid dependant Crohn's disease (CD); (2) maintenance of remission in steroid
free CD; (3) azathioprine failures in CD; (4) in combination therapy with Anti
TNF agents in CD; (5) decreasing antibody formation to Anti-TNF therapy in CD;
(6) management of fistulizing disease in CD; and (7) as well as induction and
maintenance of remission in ulcerative colitis. An easy to use algorithm is
provided for the busy clinician to access and safely prescribe methotrexate for
their inflammatory bowel disease patients.
PMID- 25133042
TI - Approach to Helicobacter pylori infection in geriatric population.
AB - The prevalence of Helicobacter pylori (H. pylori) infection and its complications
increase with age. The majority of infected individuals remain asymptomatic
throughout the life but 10%-20% develops peptic ulcer disease and 1% gastric
malignancies. The incidence of ulcers and their complications are more common in
the older population resulting in higher hospitalization and mortality rates. The
increased use of medications causing gastric mucosal damage and the decreased
secretion of protective prostaglandins in elderly are major factors increasing
gastric mucosal sensitivity to the destructive effects of H. pylori. Due to
higher prevalence of gastrointestinal (GI) malignancies, upper GI endoscopy is
mostly preferred in elderly for the diagnosis of infection. Therefore, "endoscopy
and treat" strategy may be more appropriate instead of "test and treat" strategy
for dyspeptic patients in older age. Urea breath test and stool antigen test can
be used for control of eradication, except for special cases requiring follow-up
with endoscopy. The indications for treatment and suggested eradication regimens
are similar with other age groups; however, the eradication failure may be a more
significant problem due to high antibiotic resistance and low compliance rate in
elderly. Multidrug usage and drug interactions should always be considered before
starting the treatment. This paper reviews briefly the epidemiology, diagnosis,
disease manifestations, and treatment options of H. pylori in the geriatric
population.
PMID- 25133043
TI - Pharmacological therapy of feed intolerance in the critically ills.
AB - Feed intolerance in the setting of critical illness is associated with higher
morbidity and mortality, and thus requires promptly and effective treatment.
Prokinetic agents are currently considered as the first-line therapy given issues
relating to parenteral nutrition and post-pyloric placement. Currently, the
agents of choice are erythromycin and metoclopramide, either alone or in
combination, which are highly effective with relatively low incidence of cardiac,
hemodynamic or neurological adverse effects. Diarrhea, however, can occur in up
to 49% of patients who are treated with the dual prokinetic therapy, which is not
associated with Clostridium difficile infection and settled soon after the
cessation of the drugs. Hence, the use of prokinetic therapy over a long period
or for prophylactic purpose must be avoided, and the indication for ongoing use
of the drug(s) must be reviewed frequently. Second line therapy, such as total
parenteral nutrition and post-pyloric feeding, must be considered once adverse
effects relating the prokinetic therapy develop.
PMID- 25133045
TI - Inflammatory bowel diseases: Current problems and future tasks.
AB - Current knowledge on inflammatory bowel disease (IBD) is mainly endorsed by
controlled trials and epidemiologic studies. Yet, we seldom look at the messages
from real-world practice. Among a patient population followed since 2008, we
looked at an unselected sample of 64 IBD patients [26 Crohn's disease (CD) and 38
ulcerative colitis (UC)] who had been seen as out-patients in the last year.
Inducing remission, mesalamines (86% for UC/69% for CD/33%-16% as MMX
formulation) prevailed as prescriptions; steroids (55%/19% for UC/CD) ranked
second. Prescription of third-party drugs (antibiotics, NSAIDs, biologics) and
adherence, were issues in the maintenance. 34% of CD, and 23% of UC patients
showed accompanying immunologic diseases: CD-associated familiar psoriasis (4:9)
ranked first. Main Message. The association between IBD (CD mainly) and
psoriasis, now found in our practice, matches current basic science gathering IBD
together with psoriasis (and perhaps chronic respiratory disease) under the
comprehensive term "barrier organ disease" wherein an epithelial surface with
sensor systems rules contacts between outer antigens and a reactive underneath
tissue, with the balance between inflammation and quiescence kept at any time by
mucosal permeability. IBD is thus viewed as a polyfactorial/polygenic/syndromic
disorder, embedded into a galaxy of immune conditions offering multiple points of
attack. This mindset of splitting the IBDs into pathogenic categories may allow
overcoming the uniformly targeting of a single cytokine by biological drugs, in
favor of demarcating the boundaries between different disease-subtype-specific
indications, and paving the way to future personalized strategies.
PMID- 25133041
TI - Visceral hypersensitivity and electromechanical dysfunction as therapeutic
targets in pediatric functional dyspepsia.
AB - Functional gastrointestinal disorders (FGID) are common clinical syndromes
diagnosed in the absence of biochemical, structural, or metabolic abnormalities.
They account for significant morbidity and health care expenditures and are
identifiable across variable age, geography, and culture. Etiology of abdominal
pain associated FGIDs, including functional dyspepsia (FD), remains incompletely
understood, but growing evidence implicates the importance of visceral
hypersensitivity and electromechanical dysfunction. This manuscript explores data
supporting the role of visceral hypersensitivity and electromechanical
dysfunction in FD, with focus on pediatric data when available, and provides a
summary of potential therapeutic targets.
PMID- 25133044
TI - Renal dysfunction in patients with cirrhosis: Where do we stand?
AB - Patients with cirrhosis and renal failure are high-risk patients who can hardly
be grouped to form precise instructions for diagnosis and treatment. When it
comes to evaluate renal function in patients with cirrhosis, determination of
acute kidney injury (AKI), chronic kidney disease (CKD) or AKI on CKD should be
made. First it should be excluded the prerenal causes of AKI. All cirrhotic
patients should undergo renal ultrasound for measurement of renal resistive index
in every stage of liver dysfunction and urine microscopy for differentiation of
all causes of AKI. If there is history of dehydration on the ground of normal
renal ultrasound and urine microscopy the diuretics should be withdrawn and
plasma volume expansion should be tried with albumin. If the patient does not
respond, the correct diagnosis is HRS. In case there is recent use of nephrotoxic
agents or contrast media and examination shows shock, granular cast in urinary
sediment and proteinuria above 0.5 g daily, acute tubular necrosis is the
prominent diagnosis. Renal biopsy should be performed when glomerular filtration
rate is between 30-60 mL/min and there are signs of parenchymal renal disease.
The acute renal function is preferable to be assessed with modified AKIN.
Patients with AKIN stage 1 and serum creatinine >= 1.5 mg/dL should be at close
surveillance. Management options include hemodynamic monitoring and management of
fluid balance and infections, potentially driving to HRS. Terlipressin is the
treatment of choice in case of established HRS, administered until there are
signs of improvement, but not more than two weeks. Midodrine is the alternative
for therapy continuation or when terlipressin is unavailable. Norepinephrine has
shown similar effect with terlipressin in patients being in Intensive Care Unit,
but with much lower cost than that of terlipressin. If the patient meets the
requirements for transplantation, dialysis and transjugular intrahepatic
portosystemic shunt are the bridging therapies to keep the transplant candidate
in the best clinical status. The present review clarifies the latest therapeutic
modalities and the proposed recommendations and algorithms in order to be applied
in clinical practice.
PMID- 25133046
TI - Prevention of hepatocellular carcinoma in patients with chronic hepatitis B.
AB - Patients with chronic hepatitis B are at significant risk for hepatocellular
carcinoma (HCC). Globally, over half a million people each year are diagnosed
with HCC, with marked geographical variations. Despite overwhelming evidence for
a causal role of hepatitis B virus (HBV) infection in the development of HCC and
a well-established relationship between high baseline hepatitis B viral load and
cumulative risk of HCC, the molecular basis for this association has not been
fully elucidated. In addition, a beneficial role for antiviral therapy in
preventing the development of HCC has been difficult to establish. This review
examines the biological and molecular mechanisms of HBV-related
hepatocarcinogenesis, recent results on the effect of modern nucleos(t)ides on
the rate of HCC development in high risk HBV cohorts and the potential mechanisms
by which long-term antiviral therapy with potent inhibitors of HBV replication
might reduce the risk of HCC in patients with chronic hepatitis B. Although
evidence from randomized controlled trials shows the favourable effects of
antiviral agents in achieving profound and durable suppression of HBV DNA levels
while improving liver function and histology, robust evidence of other long-term
clinical outcomes, such as prevention of HCC, are limited.
PMID- 25133047
TI - Ischemic heart disease, factor predisposing to Barrett's adenocarcinoma: A case
control study.
AB - AIM: To define the significance of ischemic heart disease (IHD) (stable angina to
infarction) co-existance in Barrett esophagus (BE) patients and patients with
esophageal adenocarcinoma (AdE). METHODS: All BE/AdE patients in Blackpool-Wyre
Fylde area and Trikala prefecture identified from medical records. Patient
clinical details were obtained from hospital and General Practitioner records.
Additional information was gathered from validated questionnaire. RESULTS: Forty
(33%) AdE and 83 (19%) BE patients had IHD (P = 0.002). Eighteen (15%) AdE and 34
(8%) BE patients had suffered a myocardial infarction (P = 0.03). Three (3%) AdE
and 7 (2%) BE patients had severe heart failure (P = 0.82). Thirty-nine (47%) BE
with IHD and 8 (20%) AdE patients with IHD consumed aspirin daily (P = 0.004).
Seventh-seven (93%) BE patients with IHD and 36 (90%) AdE patients with IHD were
on statins (P = 0.86). Logistic regression analysis: AdE was more frequent in the
elderly, with long term reflux, long BE and concurrent IHD (odds ratio: 2.086, P
= 0.001) not consuming statins. Eighteen (22%) BE patients with IHD [16 (84%)
with myocardial infarction] vs 33 (10%) without IHD died from non-neoplastic
causes within 24 mo from BE diagnosis (P = 0.005). CONCLUSION: IHD is more
prevalent in AdE than BE patients. Increased prevalence of AdE is related with
the presence of myocardial infarction but not severe heart failure, possibly
because patients with BE and severe IHD have low life expectancy.
PMID- 25133048
TI - Statins and their role in acute pancreatitis: Case report and literature review.
AB - Statin induced pancreatitis has historically been considered a diagnosis of
exclusion, with literature references typically in the form of case reports and
observational studies. Recently, larger studies have challenged the correlations
made by earlier case reports, and instead demonstrate a mild protective effect in
statin users. We present a case report of likely statin induced pancreatitis in a
58-year-old male (which we have attributed to drug-drug interaction with
resulting inhibition of hepatic cytochrome P450 enzymes) and have reviewed the
apparent dichotomy in the available literature.
PMID- 25133049
TI - Rhabdomyolysis after midazolam administration in a cirrhotic patient treated with
atorvastatin.
AB - The administration of statins in patients with liver disease is not an absolute
contraindication. Hepatotoxicity is a rare and often dose-related event and in
the literature there are only a few described cases of fatal rhabdomyolysis in
patients with chronic liver disease after statin administration. During treatment
with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, the factors
responsible for myopathy may either be related to the patient, or due to
interactions with other medications that are metabolic substrates of the same
isozymes and therefore able to increase blood statin concentration. The most
important side effects consist of increased transaminase levels, abdominal pain
or muscle weakness, increased serum levels of creatine kinase and rhabdomyolysis.
In this article we report a case of fatal rhabdomyolysis with acute renal failure
after gastric endoscopy, where midazolam was used as a sedation agent in a
patient with chronic liver disease treated with a high dose of atorvastatin.
Therefore, we suggest paying particular attention to the potential risks of
associating atorvastatin and midazolam in patients with chronic liver disease who
need to undergo gastric endoscopy.
PMID- 25133050
TI - Can primary care sleep medicine integration work?
AB - Sleep disorders are common in the veteran population. There is an increasing need
for sleep medicine services in returning veterans. Primary care providers are
uncomfortable diagnosing and treating sleep disorders. Patients often have to
wait several days before they can be seen by a sleep clinician. This pilot
project evaluated the feasibility of providing sleep medicine services to
patients in a primary care setting. Primary care providers were involved in
decision-making, resulting in improved satisfaction with sleep medicine services
among primary care clinicians.
PMID- 25133051
TI - Negative rumor: contagion of a psychiatric department.
AB - Over the past few decades, a sizable body of literature on the effects of rumors
and gossip has emerged. Addressing rumors in the workplace is an important
subject, as rumors have a direct impact on the quality of the work environment
and also on the productivity and creativity of the employees. To date, little has
been written on the effect of rumors and gossip in psychiatric hospitals. This
article presents case vignettes of rumors spread in psychiatric hospitals and the
impact on team cohesion and morale among the staff implicated in these, too
often, neglected occurrences. Dynamic aspects with particular focus on rumors in
psychiatric units and suggestions for remedy and treatment are presented.
PMID- 25133053
TI - Lithium-induced fixed drug eruption in a case of bipolar mania.
PMID- 25133054
TI - DSM-5 Drops the 5 Axes of Mysticism: A Supportive Survey.
PMID- 25133052
TI - Psychotic disorders in children and adolescents: a primer on contemporary
evaluation and management.
PMID- 25133055
TI - Lithium-induced transient euthyroid hyperthyroxinemia: a case report.
PMID- 25133056
TI - A new perspective on gender dysphoria and repetitive sex reassignment surgeries:
a case report.
PMID- 25133057
TI - Secondary psychosis 3 months prior to the overt symptoms of multiple myeloma: a
case report.
PMID- 25133058
TI - A case report of the use of vilazodone in pregnancy.
PMID- 25133059
TI - Nystagmus as a discontinuation symptom after antidepressant therapy: a case
report.
PMID- 25133060
TI - A survey of patients' knowledge about lithium therapy in the elderly.
AB - OBJECTIVE: Lithium is commonly used in the treatment of various psychiatric
disorders. It has a narrow therapeutic range and a mortality rate of 9% in
patients intoxicated during maintenance therapy. Therefore, for lithium to be
prescribed safely, clinicians must ensure that patients are aware of features of
lithium toxicity. We aim to identify patients' knowledge of lithium in the
elderly population and associated factors that may influence this knowledge.
METHOD: The Lithium Knowledge Test (LKT) is a brief questionnaire that was
developed as a means of identifying patients' practical and pharmacologic
knowledge, which is important if therapy is to be safe and effective. The survey
was conducted in the outpatient service of the Department of Old Age Psychiatry
attached to a university teaching hospital in an urban area in Ireland between
January 2011 and July 2011. A total of 33 patients participated in the survey,
and the LKT questionnaires were completed by all participants. The LKT scores are
obtained by adding up the responses to the questions, while the LKT hazard scores
are obtained by adding together the responses to the questions on symptoms of
toxicity. The result was analyzed using SPSS version 20 (SPSS Inc, Chicago,
Illinois), and the relationships between LKT scores and LKT hazard scores as well
as other variables were examined using Pearson's correlation coefficient.
RESULTS: The mean LKT score of our sample population was 4.45, suggestive of poor
knowledge of lithium, and the mean LKT hazard score was 5.85, highly suggestive
of potentially hazardous lack of knowledge. There was a significant negative
correlation between the LKT score and hazard score (r = -0.65, P < .01 [1
tailed]). CONCLUSIONS: The survey results highlight the need for patients to be
given comprehensive information about lithium prior to commencement of treatment
and a refresher educational program during lithium therapy.
PMID- 25133061
TI - Association of hypnotics with stroke risk: a population-based case-control study.
AB - BACKGROUND: The aim of this study was to determine what association, if any,
hypnotics have on the risk of stroke events. METHOD: In a nationwide population
based case-control study, cases were patients with incident stroke diagnosed
between January 1, 2006, and December 31, 2006. Patients with hemorrhagic or
ischemic stroke diagnosis codes (ICD-9-CM codes 430-438) and who had been
hospitalized for further treatment were included in the study. Patients with any
type of stroke diagnosed before 2006 were excluded. The authors selected 2,779
stroke patients and 27,790 controls matched for age, gender, physician visit
date, and comorbidities. The impact of hypnotics on stroke was examined by
multiple logistic regression models and sensitivity analyses. RESULTS:
Individuals prescribed any hypnotic had elevated risk of stroke compared to those
prescribed no hypnotics. For groups prescribed 1-27, 28-148, and >= 149 pills,
odds ratios for stroke were 1.71 (95% CI, 1.49-1.96), 1.84 (95% CI, 1.62-2.11),
and 1.45 (95% CI, 1.26-1.68), respectively. Adjusted odds ratios were elevated in
separate analyses for zolpidem and estazolam. The observed results were robust
with stratification by comorbidities, such as hypertension and diabetes, and
using ischemic stroke as the case group. CONCLUSIONS: This study shows that, in a
case-control study matched for age, gender, and comorbidities using multiple
logistic regression and sensitivity tests, zolpidem and estazolam were slightly
associated with an increased risk of stroke. Further large-scale and in-depth
studies should be performed. Use of hypnotics should always be determined by
specialists, and adverse effects should be continuously monitored.
PMID- 25133062
TI - Acute interventions and referral of patients with bipolar disorder by the
psychiatric consultation liaison service in a general hospital in Germany: a
retrospective analysis.
AB - OBJECTIVE: To investigate the population of bipolar patients in a general
hospital in Germany who required treatment by a consultant psychiatrist. METHOD:
A retrospective analysis was conducted of the clinical records of 47 patients
diagnosed with bipolar disorder (DSM-IV-TR criteria) who were treated by a
consultant psychiatrist between 2009 and 2012 in one of the general hospitals of
Charite Berlin, Campus Benjamin Franklin, Berlin, Germany. We investigated the
sections of the hospital that requested psychiatric consultations for bipolar
patients, the status of these patients, and their primary cause of treatment, as
well as the intervention (including pharmacotherapy) recommended by the
consultant psychiatrist. RESULTS: For more than half of the patients, their
psychiatric illness was either directly or indirectly the reason they presented
to the hospital. The remaining bipolar patients were treated for various somatic
illnesses unrelated to their bipolar disorder throughout the hospital, with a
relative overrepresentation of patients in the neurology department. More than
half of the patients were referred to a psychiatric hospital by the consultant
psychiatrist. Benzodiazepines were the most commonly administered drugs for acute
pharmacologic intervention. CONCLUSIONS: Psychiatric consultations are not
frequently requested for bipolar patients compared to those with other
psychiatric disorders. However, more than half of the bipolar patients needed
further psychiatric treatment in a psychiatric hospital. This finding emphasizes
the importance of psychiatric consultations in a general hospital for bipolar
patients. The administration of benzodiazepines as an acute treatment seems to be
the standard pharmacologic procedure, not a specific pharmacotherapy like mood
stabilizers.
PMID- 25133063
TI - Mixed Specifier for Bipolar Mania and Depression: Highlights of DSM-5 Changes and
Implications for Diagnosis and Treatment in Primary Care.
AB - Bipolar disorder, while commonly encountered in the primary care setting, is
often misdiagnosed or undiagnosed. In the DSM-IV-TR, patients could be diagnosed
as being in a mixed state only if they had concurrent manic and depressive
symptoms; while this occurs in some patients, many more experience subsyndromal
mixed symptoms that would disqualify a "mixed state" diagnosis. The recently
released DSM-5 attempts to capture this large proportion of patients with
subsyndromal mixed symptoms with the inclusion of the "mixed specifier." The
presence of such subsyndromal mixed symptoms has significant implications for
both diagnosis and treatment. For those presenting with major depressive disorder
with subsyndromal manic symptoms, clinicians must be vigilant for the development
of full-blown bipolar disease. In treating this group, selective serotonin
reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors remain first
line therapy, but augmentation with other therapies is often required. If a
diagnosis of bipolar disorder is confirmed and the patient is experiencing a
depressive phase, traditional antidepressants should be avoided. For those
presenting with mania and mixed depressive symptoms, treatment with a combination
of atypical antipsychotics and mood stabilizers is best.
PMID- 25133064
TI - Coping with helplessness.
PMID- 25133065
TI - Multimedia Informed Consent Tool for a Low Literacy African Research Population:
Development and Pilot-Testing.
AB - BACKGROUND: International guidelines recommend the use of appropriate informed
consent procedures in low literacy research settings because written information
is not known to guarantee comprehension of study information. OBJECTIVES: This
study developed and evaluated a multimedia informed consent tool for people with
low literacy in an area where a malaria treatment trial was being planned in The
Gambia. METHODS: We developed the informed consent document of the malaria
treatment trial into a multimedia tool integrating video, animations and audio
narrations in three major Gambian languages. Acceptability and ease of use of the
multimedia tool were assessed using quantitative and qualitative methods. In two
separate visits, the participants' comprehension of the study information was
measured by using a validated digitised audio questionnaire. RESULTS: The
majority of participants (70%) reported that the multimedia tool was clear and
easy to understand. Participants had high scores on the domains of adverse
events/risk, voluntary participation, study procedures while lowest scores were
recorded on the question items on randomisation. The differences in mean scores
for participants' 'recall' and 'understanding' between first and second visits
were statistically significant (F (1,41)=25.38, p<0.00001 and (F (1, 41) = 31.61,
p<0.00001 respectively. CONCLUSIONS: Our locally developed multimedia tool was
acceptable and easy to administer among low literacy participants in The Gambia.
It also proved to be effective in delivering and sustaining comprehension of
study information across a diverse group of participants. Additional research is
needed to compare the tool to the traditional consent interview, both in The
Gambia and in other sub-Saharan settings.
PMID- 25133066
TI - Microbial Infection and Rheumatoid Arthritis.
AB - Rheumatoid arthritis (RA) is a complex autoimmune disease affecting 1-2% of
general worldwide population. The etiopathogenesis of RA involves the interplay
of multiple genetic risk factors and environmental triggers. Microbial infections
are believed to play an important role in the initiation and perpetuation of RA.
Recent clinical studies have shown the association of microbial infections with
RA. Accumulated studies using animal models have also found that microbial
infections can induce and/or exaggerate the symptoms of experimental arthritis.
In this review, we have identified the most common microbial infections
associated with RA in the literature and summarized the current evidence
supporting their pathogenic role in RA. We also discussed the potential
mechanisms whereby infection may promote the development of RA, such as
generation of neo-autoantigens, induction of loss of tolerance by molecular
mimicry, and bystander activation of the immune system.
PMID- 25133067
TI - Astrocyte Reactivity: A Biomarker for Retinal Ganglion Cell Health in Retinal
Neurodegeneration.
AB - Retinal ganglion cell (RGC) loss in glaucoma is sectorial in nature and preceded
by deficits in axonal transport. Neuroinflammation plays an important role in the
pathophysiology of glaucoma in the retina, optic nerve and visual centers of the
brain, where it similarly appears to be regulated spatially. In a murine model,
we examined the spatial characteristics of astrocyte reactivity
(migration/proliferation, hypertrophy and GFAP expression) in healthy retina,
retina with two glaucoma-related risk factors (aging and genetic predisposition)
and glaucomatous retina and established relationships between these reactivity
indices and the spatial organization of astrocytes as well as RGC health.
Astrocyte reactivity was quantified by morphological techniques and RGC health
was determined by uptake and transport of the neural tracer cholera toxin beta
subunit (CTB). We found that: (1) astrocyte reactivity occurs in microdomains
throughout glaucomatous retina as well as retina with risk factors for glaucoma,
(2) these astrocyte microdomains are primarily differentiated by the degree of
retinal area covered by the astrocytes within them and (3) percent retinal area
covered by astrocytes is highly predictive of RGC health. Our findings suggest
that microdomains of astrocyte reactivity are biomarkers for functional decline
of RGCs. Based on current and emerging imaging technologies, diagnostic
assessment of astrocytes in the nerve fiber layer could succeed in translating
axonal transport deficits to a feasible clinical application.
PMID- 25133069
TI - Elevating quality with manditory use of standard reporting guidelines.
AB - The Editorial staff of The International Journal of Sports Physical Therapy
(IJSPT) is dedicated to the review, critical appraisal, and publication of high
quality scientific and clinical research, systematic reviews, meta-analyses, and
case reports. As IJSPT progresses through its' ninth year of providing high
quality research evidence as well as relevant clinical commentary and suggestions
for the international sports physical therapy community, we offer the following
editorial. We, along with many other prestigious journals are committed to
elevating the quality of published research related to disability and
rehabilitation and agree to adherence to the following reporting guidelines,
which will be required by IJSPT as of January 1, 2015. Many of these guidelines
are all ready in place and have been implemented by IJSPT. This Editorial is a
reprint of a previously published Editorial in The Archives of Physical Medicine
and Rehabilitation, and is used with permission.
(http://dx.doi.org/10.1016/j.apmr.2013.12.010) FOR CITATION PURPOSES, PLEASE USE
THE ORIGINAL PUBLICATION DETAILS: Chan L, Heinemann AW, and Roberts J, Elevating
the Quality of Disability and Rehabilitation Research: Mandatory use of the
Reporting Guidelines. Archives of Physical Medicine and Rehabilitation, 2014: 95:
414-417.
PMID- 25133068
TI - The Pathogenesis of Lupus Nephritis.
AB - Lupus nephritis is a serious potential feature of systemic lupus erythematous
(SLE). Though SLE typically cycles through periods of flares and remission,
patients often eventually succumb to end-stage kidney or cardiovascular damage.
This review of the pathogenesis of lupus nephritis examines the role of the
complement cascade; the significance of autoantibodies, the breaking of
tolerance, and the implications of altered apoptosis in breaking tolerance; and
the contributions of adaptive immunity and cross-talk with the innate immune
system in driving renal damage. Delineation of basic mechanisms underlying the
development of acute and chronic renal damage in lupus nephritis can result in
the continued development of more specific and effective treatments.
PMID- 25133070
TI - The validity of 2-dimensional measurement of trunk angle during dynamic tasks.
AB - PURPOSE/BACKGROUND: Injury screening methods that use three-dimensional (3D)
motion analysis accurately predict the risk of injuries, yet are expensive. There
is great need for valid, cost-effective techniques that can be used in large
scale assessments. Utilizing two-dimensional (2D) measures of lateral trunk
motion may identify athletes at risk for lower extremity injury. The purpose of
this research was to determine the strength of the relationships between 2D and
3D calculations of lateral trunk angle for female athletes performing a single
leg cross drop landing. METHODS: Twenty-one high-school female volleyball players
performed a single-leg cross drop landing onto a force plate. The 3D angular
trunk motion was calculated, and four different 2D measures of lateral trunk
angle were calculated for both left and right landing leg. A one-way multivariate
analysis of variance was used to compare 2D measures to the 3D measurements, and
Pearson correlations were used to determine the strength of these relationships.
RESULTS: The angle formed by the medial shoulder joint center, medial ASIS, and
vertical line (LTA4) was similar to the 3D measures of lateral trunk angle during
landing (r-values >= 0.62; p-values <= 0.003; mean differences, -1.0 degrees to
1.2 degrees ). CONCLUSIONS: Given the recent focus on the role of the trunk in
lower extremity injury, using the 2D LTA4 assessment may expand existing
assessments into a composite model that can more accurately assess female
athletes at risk for injury than models that do not include trunk analysis.
CLINICAL RELEVANCE: Existing models that enable clinicians to effectively
identify female athletes at risk for lower extremity injury may be enhanced by
including accurate assessments of lateral trunk motion.
PMID- 25133071
TI - Comparison of the immediate effect of different types of trunk exercise on the
star excursion balance test in male adolescent soccer players.
AB - PURPOSE/BACKGROUND: Trunk exercises, such as trunk stabilization exercises (SE)
and conventional trunk exercises (CE), are performed to improve static or dynamic
balance. Recently, trunk exercises have also been often used as part of warm-up
programs. A few studies have demonstrated the immediate effects of SE and CE on
static balance. However, immediate effects on dynamic balance are not yet known.
Therefore, the purpose of this study was to compare the immediate effect of SE
with that of CE on the Star Excursion Balance Test (SEBT). METHODS: Eleven
adolescent male soccer players (17.9 +/- 0.3 years, 168.5 +/- 5.4 cm, and 60.1 +/
5.1 kg) participated in this study. A crossover design was used, and each
participant completed three kinds of testing sessions: SE, CE, and non-exercise
(NE). Experiments took place for three weeks with three testing sessions, and a 1
week interval was provided between different conditions. Each testing session
consisted of three steps: pretest, intervention, and posttest. To assess dynamic
balance, the SEBT score in the anterior, posteromedial, and posterolateral
directions was measured before and 5 minutes after each intervention program. The
data of reach distance were normalized with the leg length to exclude the
influence of the leg length on the analysis. RESULTS: The SEBT composite score
was significantly improved after the SE (p < 0.05) but did not change after the
CE and NE (p > 0.05). Furthermore, in the SE condition, SEBT scores of the
posterolateral and posteromedial directions were significantly improved at the
posttest, compared with those at the pretest (p < 0.05). CONCLUSIONS: This study
demonstrated the immediate improvements in the posteromedial and posterolateral
directions of the SEBT only after the SE. This result suggests that the SE used
in this study is effective in immediately improving dynamic balance. LEVELS OF
EVIDENCE: 3b.
PMID- 25133072
TI - Effects of postural control manipulation on visuomotor training performance:
comparative data in healthy athletes.
AB - PURPOSE/BACKGROUND: Visuomotor ability is an important parameter for neurologic
function and effective sport performance. Adding a balance challenge during a
structured eye-hand coordination task, such as hitting lights on a light board
(DynavisionTM), has not been previously reported. Using Division I football
players, the aim of this study was to determine normative data on a dual-task
performance regimen combining a visuomotor light board task with a balance task.
The intent is to use such normative data and baseline data as part of a
concussion management program. METHODS: Division I college football team members,
n=105, were consented. Subjects first performed DynavisionTM D2TM Visuomotor
Training Device (D2TM) eye-hand coordination tasks, the A* and the RT; they then
performed the same tasks with an added balance challenge, standing on a BOSU(r)
ball. RESULTS: Ninety-four athletes completed the full testing procedure on the
D2TM system. The mean score of the A* test was 93 +/- 11.0 hits per minute; and
the mean on the A* test with the added BOSU(r) balance challenge was 83.7 +/- 9.2
hits per minute. The mean RT time was 0.33 +/- 0.036 seconds. Mean reaction time
increased to 0.38 +/- 0.063 while the subject stood on the BOSU(r) ball.
Performance on the D2TM A* and RT were both statistically significantly different
in the dual task condition (p<0.05). CONCLUSIONS: Results show an approximate 10%
decline in D2TM performance when healthy individuals stand on a BOSU(r) ball.
From the data presented here, the authors determined that there is a 10%
decrement in performance when one's balance is challenged on the BOSU(r) ball. A
fall in performance of substantially greater than 10% may indicate abnormal
vestibulocerebellar regulatory processing of balance and motion. Further
research, using these normative data is needed to determine more specific
parameters for definitions of impairment and return-to-play and if there is
utility for such studies as part of a concussion management program. LEVEL OF
EVIDENCE: III.
PMID- 25133073
TI - Off-season training habits and preseason functional test measures of division iii
collegiate athletes: a descriptive report.
AB - PURPOSE/BACKGROUND: Division III (D III) collegiate coaches are challenged to
assess athletic readiness and condition their athletes during the preseason.
However, there are few reports on off-season training habits and normative data
of functional assessment tests among D III athletes. The purpose of this study
was to examine off-season training habits of D III athletes and their
relationships to the standing long jump (SLJ) and single-leg hop (SLH) tests.
METHODS: One-hundred and ninety-three athletes (110 females, age 19.1 +/- 1.1 y;
83 males, age 19.5 +/- 1.3 y) were tested prior to the start of their sports
seasons. Athletes reported their off-season training habits (weightlifting,
cardiovascular exercise, plyometric exercise, and scrimmage) during the six weeks
prior to the preseason. Athletes also performed three maximal effort SLJs and
three SLHs. RESULTS: Male athletes reported training more hours per exercise
category than their female counterparts. Mean SLJ distances (normalized to
height) were 0.79 +/- 0.10 for females and 0.94 +/- 0.12 for males. Mean SLH
distances for female athletes' right and left limbs were 0.66 (+/- 0.10) and 0.65
(+/- 0.10), respectively. Mean SLH distances for male athletes' right and left
limbs were 0.75 (+/- 0.13) and 0.75 (+/- 0.12), respectively. Several significant
differences between off-season training habits and functional test measures were
found for both sexes: males [SLJ and weightlifting (p = 0.04); SLH and
weightlifting (p = 0.04), plyometrics (p = 0.05)]; females [SLJ and plyometrics
(p = 0.04); SLH and scrimmage (p = 0.02)]. CONCLUSION: This study provides
normative data for off-season training habits and preseason functional test
measures in a D III athlete population. Greater SLJ and SLH measures were
associated with increased time during off-season training. CLINICAL RELEVANCE:
The findings between functional tests and off-season training activities may be
useful for sports medicine professionals and strength coaches when designing
their preseason training programs. LEVEL OF EVIDENCE: 4.
PMID- 25133074
TI - Reduced hip strength is associated with increased hip motion during running in
young adult and adolescent male long-distance runners.
AB - STUDY DESIGN: Controlled laboratory study. BACKGROUND AND PURPOSE: Anterior knee
pain is one of the most common running symptoms reported in the literature. While
the exact etiology is unknown, a lack of hip strength is suggested to contribute
to abnormal running mechanics. The purpose of this research study was to evaluate
the association between isokinetic hip strength and 3-D running kinematics.
METHODS: 33 male high school and collegiate cross country runners participated in
this study. Peak isokinetic hip abductor and hip extensor strength were assessed.
Each subject also completed a treadmill running protocol at a self-selected speed
(mean = 3.8 m/s). 3-D kinematic data were collected at 240 Hz using a 10-camera
motion capture system. Pearson correlation coefficients were used to determine
the relationship between hip strength and hip range of motion (ROM) during the
stance phase of running (p<0.05). RESULTS: Peak isokinetic hip extensor torque
was inversely correlated with transverse plane hip ROM (r = -.387, p = .026) but
was not significantly related to sagittal plane hip ROM or frontal plane hip ROM.
Peak isokinetic hip abductor torque was inversely correlated with frontal plane
hip ROM (r=-.462, p=.008) but was not significantly related to either sagittal
plane hip ROM or transverse plane hip ROM. Peak isokinetic hip extensor torque
and peak isokinetic hip abductor torque were not significantly related to knee
kinematics in any plane. CONCLUSIONS: Peak isokinetic hip extensor torque and
peak isokinetic hip abductor torque are associated with transverse plane and
frontal plane hip kinematics, but not knee kinematics. LEVELS OF EVIDENCE: Level
3b.
PMID- 25133075
TI - Patellofemoral pain subjects exhibit decreased passive hip range of motion
compared to controls.
AB - BACKGROUND: Patellofemoral pain is a common condition without a clear mechanism
for its presentation. Recently significant focus has been placed on the hip and
its potential role in patellofemoral pain (PFP). The majority of the research has
examined hip strength and neuromuscular control. Less attention has been given to
hip mobility and its potential role in subjects with PFP. PURPOSE/AIM: The
purpose of this study was to compare passive hip range of motion (ROM) of hip
extension and hip internal and external rotation in subjects with PFP and healthy
control subjects. The hypothesis was that subjects with PFP would present with
less total hip ROM and greater asymmetry than controls. DESIGN: Two groups, case
controlled. SETTING: Clinical research laboratory. PARTICIPANTS: 30 healthy
subjects without pain, radicular symptoms or history of surgery in the low back
or lower extremity joints and 30 subjects with a diagnosis of PFP. MAIN OUTCOME
MEASURES: Passive hip extension, hip internal rotation (IR) and hip external
rotation (ER). A digital inclinometer was used for measurements. RESULTS: There
was a statistically significant difference (p<0.001) in hip passive extension
between the control group and the PFP group bilaterally. Mean hip extension for
the control group was 6.8 degrees bilaterally. For the PFP group, the mean hip
extension was -4.0 degrees on the left and -4.3 degrees on the right. This
corresponds to a difference of means between groups of 10.8 degrees on the left
and 11.1 degrees on the right with a standard error of 2.1 degrees . There was
no statistically significant difference (p>0.05) in either hip IR or ER ROM or
total rotation between or within groups. CONCLUSIONS: The results of this study
indicate that a significant difference in hip extension exists in subjects with
PFP compared to controls. These findings suggest that passive hip extension is a
variable that should be included within the clinical examination of people with
PFP. It may be valuable to consider hip mobility restrictions and their potential
impact on assessment of strength and planned intervention in subjects with PFP.
LEVEL OF EVIDENCE: 2b.
PMID- 25133076
TI - Effect of ankle braces on lower extremity muscle activation during functional
exercises in participants with chronic ankle instability.
AB - BACKGROUND: Ankle bracing and rehabilitation are common methods to reduce the
rate of recurrent ankle sprain in participants with chronic ankle instability
(CAI). CAI participants utilize less muscle activity when performing functional
exercises compared to healthy controls. The effect of ankle braces on muscle
activity during functional exercises in participants with CAI has not been
previously studied. PURPOSE: To determine the effect of bracing on motor output
as demonstrated by surface EMG amplitudes in participants with CAI during single
limb, eyes closed balance, star excursion balance, forward lunge, and lateral hop
exercises. METHODS: A descriptive laboratory study was performed. Fifteen young
adults with CAI performed functional exercises with and without ankle braces
while surface EMG signals were recorded from the tibialis anterior, peroneus
longus, lateral gastrocnemius, rectus femoris, biceps femoris, and gluteus
medius. The main outcome measures were normalized surface EMG amplitudes (root
mean square area) for each muscle, muscles of the shank (distal three muscles),
muscles of the thigh (proximal three muscles), and total muscle activity (all six
muscles) of the lower extremity. A paired t-test was performed for each dependent
variable to compare conditions. The level of significance was set a priori at p
<= 0.05 for all analyses. RESULTS: During the forward lunge, bracing
significantly reduced muscle activity pre-initial contact in the lateral
gastrocnemius and post-initial contact in the peroneus longus. During the star
excursion balance anterior reach the peroneus longus, lateral gastrocnemius,
rectus femoris, and gluteus medius had significantly less muscle activity during
braced trials. Bracing significantly reduced thigh and total muscle activity
during the anterior reach and gluteus medius activity during the posterolateral
reach. There were no differences between braced and unbraced conditions during
the single limb eyes closed balance, star excursion balance posteromedial reach,
or during lateral hop exercises. CONCLUSIONS: Clinicians should be aware of the
decreased muscle activity that occurs during common rehabilitation exercises when
patients with CAI complete those activities while wearing ankle braces. LEVEL OF
EVIDENCE: Level III.
PMID- 25133077
TI - The effects of conventional physical therapy and eccentric strengthening for
insertional achilles tendinopathy.
AB - STUDY DESIGN: Single-blind, randomized, clinical trial. BACKGROUND: The effect of
eccentric training for mid-portion Achilles tendinopathy is well documented;
however, its effect on insertional Achilles tendinopathy is inconclusive. The
primary purpose of this study was to investigate the effect of eccentric training
on pain and function for individuals with insertional Achilles tendinopathy.
METHODS: All patients received a 12-week conventional strengthening protocol.
Patients who were randomly assigned to the experimental group received additional
eccentric exercises. Patients completed the Short Form-36 Health and Bodily Pain
Surveys, the Foot and Ankle Outcomes Questionnaire, and the Visual Analog Scale
at initial evaluation, after 6 weeks of therapy, and at 12 weeks after therapy.
RESULTS: Thirty-six patients (20 control and 16 experimental; average age 54
years; 72% women) completed the study. Both groups experienced statistically
significant decreases in pain and improvements in function. No statistically
significant differences were noted between the groups for any of the outcome
measures. CONCLUSION: Conventional physical therapy consisting of gastrocnemius,
soleus and hamstring stretches, ice massage on the Achilles tendon, and use of
heel lifts and night splints with or without eccentric training is effective for
treating insertional Achilles tendinopathy. LEVEL OF EVIDENCE: Level 2.
PMID- 25133078
TI - A comparison of range of motion change across four posterior shoulder tightness
measurements after external rotator fatigue.
AB - BACKGROUND: Several glenohumeral joint (GHJ) positions have been recommended for
assessing and correcting posterior shoulder tightness (PST) however, there is no
agreement on which position is better for differentiating posterior muscle
tightness from posterior capsular tightness. The purpose of this study was to
compare the range of motion change before and after an external humeral rotator
muscle fatigue protocol in order to identify a position that shows maximum range
of motion change. METHODS: ROM changes across four PST measurements were compared
before, immediately after, at 24 hours after, and 48 hours after an external
rotator fatigue protocol. Muscle stiffness of the infraspinatus and the teres
minor (using a myotonometer) and external rotation force production (using hand
held dynamometry) were measured to verify muscle fatigue. RESULTS: There was a
statistically significant interaction between measurement and condition (F =
2.47, p = 0.02). The planned one factor repeated measure ANOVA for each condition
revealed that ROM change was statistically significant between PST measurements
for all conditions. Post hoc comparisons indicated statistically significant
greater overall ROM changes in a measurement combining GHJ extension and internal
rotation compared to other tested measurements. There was also a main effect of
time on infraspinatus muscle stiffness (F = 10.5, p < 0.0001). Post hoc
comparison indicated a statistically significant increase in infraspinatus
stiffness immediately after the fatigue protocol (p < 0.05). CONCLUSION:
Immediate ROM reduction was observed across all the measurements except
horizontal adduction (HAD). Maximum ROM reduction after an external rotation
fatigue protocol was measured in a position of GHJ extension. CLINICAL RELEVANCE:
Posterior muscle tightness may influence the internal rotation range of motion to
a greater extent when measured in glenohumeral joint extension. LEVELS OF
EVIDENCE: II-B.
PMID- 25133079
TI - A total motion release warm-up improves dominant arm shoulder internal and
external rotation in baseball players.
AB - CONTEXT: Current literature indicates a correlation between decreased total
shoulder range of motion (ROM) and internal rotation (IR) of the dominant arm and
increased injury risk in throwers. The optimal method for increasing shoulder
ROM, improving performance, and preventing injury is unknown. It is also unknown
if treating the non-dominant arm may affect ROM on the dominant side. PURPOSE: To
explore the effect of the Total Motion Release (TMR(r)) Trunk Twist (TT) and Arm
Raise (AR) on IR and external rotation (ER) of the dominant shoulder in baseball
players compared to a traditional dynamic warm-up. DESIGN: Cohort study. SETTING:
University athletic training clinic and baseball field. PARTICIPANTS: Pitchers
(males, n = 10; age, 18.6 +/- 1.3) recruited from local baseball teams were
randomly assigned two one of two groups: TMR(r) treatment group (TMRG; n = 5) or
traditional warm-up group (TWG; n = 5). INTERVENTIONS: Baseline IR and ER
goniometry range of motion (ROM) measurements were recorded. The TMRG then
completed the TMR(r) exercises and post-intervention measurements. The TWG
completed a traditional static and dynamic warm-up (e.g., lunges, power skips,
sprints, sleeper stretch) and then completed post-intervention measurements.
Following the completion of those measurements, the TWG completed the TMR(r)
Trunk Twist and Arm Raise protocol and had post-intervention measurements
recorded once more. MAIN OUTCOME MEASURES: ROM measures for IR and ER of the
dominant shoulder. Alpha level was set at p <= 0.05. RESULTS: Significant
differences were present for IR (p = 0.025) and ER (p = 0.014) between the TMRG
and the TWG after initial intervention. Significant differences for IR were
present in the TWG between baseline and TMR(r) intervention and traditional warm
up and TMR(r) intervention. For the TWG, changes in ER were not statistically
significant at baseline, post-warm-up, or post- TMR(r) intervention. Significant
differences were not present for IR (p = 0.44) or ER (p = 0.23) between groups
once TMR(r) had been completed by both groups. CONCLUSIONS: TMR(r) produced
larger increases in IR and ER of the throwing shoulder when compared to the TWG.
Generalizability is limited, however, by the low number of participants in each
group and a potential ceiling effect of attainable ROM gains. Future studies
should examine if using a full TMR(r) treatment process is more beneficial.
Additionally, future research should compare TMR(r) intervention to other warm-up
activities or stretching protocols (e.g. resistance tubing, weighted balls) and
examine its effect across other variables (e.g., injury rates, throwing
velocity). LEVEL OF EVIDENCE: Clinical Evidence Based Level 2b.
PMID- 25133080
TI - Bilateral differences in the upper quarter function of high school aged baseball
and softball players.
AB - PURPOSE/BACKGROUND: The Upper Quarter Y Balance Test (YBT-UQ) was developed as a
way to identify upper extremity and trunk mobility in the open kinetic chain in
the reaching limb as well as midrange limitations and asymmetries of upper
extremity and core stability in the closed kinetic chain on the stabilizing limb.
Performance on the YBT-UQ is similar between genders and between limbs; however,
this has not been examined in athletes who participate in sports that result in
upper extremity asymmetries. The primary purpose of this study is to determine if
differences exist between the throwing vs. non-throwing sides in high-school
baseball and softball athletes on the YBT-UQ. METHODS: In order to complete this
forty-eight male high school baseball players and seventeen female high school
softball players were tested on the YBT-UQ. Reach distances were normalized to
arm length (% AL). Comparisons were made between the throwing (T) and non
throwing (NT) arm for each direction as well as the composite score. RESULTS: No
significant differences were observed between the T and NT arm for the medial
(NT: 98.4 +/- 8.6 %AL, T: 99.1 +/- 8.6 %AL, p=0.42), inferolateral (NT: 90.8 +/-
11.8 %AL, T: 90.3 +/- 11.5 %AL, p =0.61), superolateral (NT: 70.6 +/- 10.9 %AL,
T: 70.4 +/- 11.1 % AL, p=0.91) reaches, or the composite score (NT: 87.2 +/- 8.9
% AL, T: 86.6 +/- 8.1 %AL, p=0.72). Similarly, no differences were observed
between the male baseball and female softball players (p=0.30-0.90). CONCLUSIONS:
Based on these findings, it was concluded that there was no difference in
performance on the YBT-UQ between throwing and non-throwing limbs in high school
baseball and softball players. LEVEL OF EVIDENCE: 3.
PMID- 25133082
TI - A modified mobilization-with-movement to treat a lateral ankle sprain.
AB - INTRODUCTION AND BACKGROUND: Lateral ankle sprains (LAS) are common in sports
medicine and can result in a high rate of re-injury and chronic ankle instability
(CAI). Recent evidence supports the use on mobilizations directed at the ankle in
patients who have suffered a LAS. The Mulligan Concept of Mobilization-with
Movement (MWM) provides an intervention strategy for LASs, but requires pain-free
mobilization application and little literature exists on modifications of these
techniques. PURPOSE: To present the use of a modified MWM to treat LASs when the
traditional MWM technique could not be performed due to patient reported pain and
to assess outcomes of the treatment. CASE DESCRIPTION: The subject of this case
report is a 23 year-old female collegiate basketball player who had failed to
respond to initial conservative treatments after being diagnosed with a lateral
ankle sprain. The initial management and subsequent interventions are presented.
After re-examination, the addition of a modification of a MWM technique produced
immediate and clinically significant changes in patient symptoms. The use of the
modified-MWM resulted in full resolution of symptoms and a rapid return to full
athletic participation. OUTCOMES: After the initial application of the modified
MWM, the patient reported immediate pain-free ankle motion and ambulation.
Following a total of 5 treatments, using only the modified MWM and taping
technique, the patient was discharged with equal range of motion (ROM)
bilaterally, a decreased Disablement in the Physically Active (DPA) Scale score,
and an asymptomatic physical exam. Follow-up exam 6 weeks later indicated a full
maintenance of these results. DISCUSSION: Recent evidence has been presented to
support the use of mobilization techniques to treat patient limitations following
ankle injury; however, the majority of evidence is associated with addressing the
talar and dorsiflexion limitations. Currently, little evidence is available
regarding the use of the MWM technique designed for LASs and the expected
outcomes. This case adds to the emerging evidence supporting the use for MWMs to
treat ankle pathology and introduces a modification that may be applied in cases
where patient reported pain prevents traditional application. LEVEL OF EVIDENCE:
Level 5; Single case report.
PMID- 25133081
TI - Diagnosis and management of acute medial tibial stress syndrome in a 15 year old
female surf life-saving competitor.
AB - BACKGROUND AND PURPOSE: As the profound health and cost benefits of physical
activity to society are established and participation guidelines implemented,
health practitioners are increasingly expected to utilize efficacious and
justified injury management and prevention strategies. The complex and
multifactorial nature of sports injury makes elucidation of multiple risk factors
and how they may subtly and variably interact, difficult. The purpose of this
case report is to discuss the differential diagnosis, acute management and
rehabilitation of a case of medial tibial stress syndrome (MTSS) in a surf life
saving athlete, in the context of sports injury prevention. CASE DESCRIPTION: The
subject of this case study, a 15 year old female surf life-saving competitor,
presented to the physiotherapist (PT) with recent onset, first episode,
bilateral, diffuse posteromedial shin pain. Differential diagnosis, acute
management, rehabilitation and preventative strategies for the subject are
presented. DISCUSSION: Emerging injury surveillance research in surf life-saving
suggests minor and major trauma as primary causative factors, however, the
significance of high training volumes is likely underestimated. The influence of
biomechanical, and subtle arthrokinematic dysfunctions on established risk
factors for MTSS injury and prevention of re-injury for this subject, are also
discussed. Furthermore, the concept of preventing tibial stress fracture (TSF) by
successfully managing acute MTSS, is presented. Lastly, a critical analysis of
reliability of clinical assessment methodologies utilised with the subject is
provided. LEVEL OF EVIDENCE: Level 5; Single case report.
PMID- 25133083
TI - Functional movement screening: the use of fundamental movements as an assessment
of function-part 2.
AB - Part 1 of this two-part series (presented in the June issue of IJSPT) provided an
introduction to functional movement screening, as well as the history,
background, and a summary of the evidence regarding the reliability of the
Functional Movement Screen (FMSTM). Part 1 presented three of the seven
fundamental movement patterns that comprise the FMSTM, and the specific ordinal
grading system from 0-3, used in the their scoring. Specifics for scoring each
test are presented. Part 2 of this series provides a review of the concepts
associated with the analysis of fundamental movement as a screening system for
functional movement competency. In addition, the four remaining movements of the
FMSTM, which complement those described in Part 1, will be presented (to complete
the total of seven fundamental movements): Shoulder Mobility, the Active Straight
Leg Raise, the Trunk Stability Push-up, and Rotary Stability. The final four
patterns are described in detail, and the specifics for scoring each test are
presented, as well as the proposed clinical implications for receiving a grade
less than a perfect "3". The intent of this two part series is to present the
concepts associated with screening of fundamental movements, whether it is the
FMSTM system or a different system devised by another clinician. Such a
fundamental screen of the movement system should be incorporated into pre
participation screening and return to sport testing in order to determine whether
an athlete has the essential movements needed to participate in sports activities
at a level of minimum competency. Part 2 concludes with a discussion of the
evidence related to functional movement screening, myths related to the FMSTM,
the future of functional movement screening, and the concept of movement as a
system. LEVEL OF EVIDENCE: 5.
PMID- 25133084
TI - PERMANENT MIGRANTS TO CITIES IN CHINA: HUKOU ORIGIN AND EARNINGS AMONG MEN IN AN
ERA OF ECONOMIC TRANSFORMATION.
AB - The massive volume of internal migration in China since the late 1970s has
attracted considerable research attention. However, the integration of permanent
migrants in cities during a time of economic transformation is understudied.
Using information on earnings from the 2003 General Social Survey of China, this
research examines whether permanent migrants are economically advantaged or
disadvantaged in comparison to non-migrants in cities. We find that permanent
migrants in cities tend to be economically advantaged and that their advantage
depends more on human capital than on political capital. Nevertheless, this does
not mean that political capital can be ignored. A nuanced view requires attention
to how political and human capital jointly affect earnings in specific economic
sectors.
PMID- 25133085
TI - Impairment and Functional Interventions for Aphasia: Having it All.
AB - Aphasia, a cognitive-linguistic disorder secondary to stroke, is a frequent and
often chronic consequence of stroke with detrimental effects on autonomy and
health-related quality of life. Treatment of aphasia can be approached in a
number of ways. Impairment-based approaches that focus on training a specific
linguistic form can be implemented. Additionally, functionally oriented
intervention such as supported conversation and aphasia groups are also
frequently utilized when providing a treatment program for an individual with
aphasia. Creating a treatment approach that includes both impairment and
functional methodologies and considers how these relate to the three domains
proposed by the International Classification of Functioning Disability and Health
(ICF)-body functions and structure, activity, and participation-can provide an
individual with aphasia an optimal treatment program that is person-centered and
multi-faceted.
PMID- 25133086
TI - Adaboost face detector based on Joint Integral Histogram and Genetic Algorithms
for feature extraction process.
AB - Recently, many classes of objects can be efficiently detected by the way of
machine learning techniques. In practice, boosting techniques are among the most
widely used machine learning for various reasons. This is mainly due to low false
positive rate of the cascade structure offering the possibility to be trained by
different classes of object. However, it is especially used for face detection
since it is the most popular sub-problem within object detection. The challenges
of Adaboost based face detector include the selection of the most relevant
features from a large feature set which are considered as weak classifiers. In
many scenarios, however, selection of features based on lowering classification
errors leads to computation complexity and excess of memory use. In this work, we
propose a new method to train an effective detector by discarding redundant weak
classifiers while achieving the pre-determined learning objective. To achieve
this, on the one hand, we modify AdaBoost training so that the feature selection
process is not based any more on the weak learner's training error. This is by
incorporating the Genetic Algorithm (GA) on the training process. On the other
hand, we make use of the Joint Integral Histogram in order to extract more
powerful features. Experimental performance on human faces show that our proposed
method requires smaller number of weak classifiers than the conventional learning
algorithm, resulting in higher learning and faster classification rates. So, our
method outperforms significantly state-of-the-art cascade methods in terms of
detection rate and false positive rate and especially in reducing the number of
weak classifiers per stage.
PMID- 25133087
TI - Investigation of strained deformed state of variable stiffness rod.
AB - An equation for bending of a weighable rod with variable transversal stiffness
was proposed. On the basis of this analyses the conclusions were drawn about the
influence of parameters of construction on values of maximum sag and maximum
bending moment. The recommendations for the usage of the simplified model were
done. The example of the construction with given parameters for calculation of
stiffness and strength according to the represented mathematical models was
considered.
PMID- 25133089
TI - A characterization of Chover-type law of iterated logarithm.
AB - ABSTRACT: Let 0 < alpha <= 2 and - infinity = 1} be
a sequence of independent copies of a real-valued random variable X and set S n =
X 1+?+X n , n >= 1. We say X satisfies the (alpha,beta)-Chover-type law of the
iterated logarithm (and write X?C T L I L(alpha,beta)) if [Formula: see text]
almost surely. This paper is devoted to a characterization of X ?C T L I
L(alpha,beta). We obtain sets of necessary and sufficient conditions for X?C T L
I L(alpha,beta) for the five cases: alpha = 2 and 0 < beta 250 cm/s) were observed during computed flow dynamics analysis in
18.5% of cases. Overall, an additional procedure to ensure patency was required
in 19 bypasses intraoperatively and three during follow-up. The presence of
aortic dissection had no significant impact on debranching graft-related
complications. During multivariate analysis, retropancreatic routing to CT was
the only independent predictor of graft-related complications (P=0.006).
CONCLUSIONS: Specific visceral graft-related complications were not uncommon in
our series and were often associated with clinical consequences. Hemodynamic
alterations of debranching grafts were observed in particular at the level of the
anastomosis with the superior mesenteric artery. Careful follow-up is mandatory
in order to monitor visceral bypasses and facilitate patency when required.
PMID- 25133103
TI - Frozen elephant trunk surgery in type B aortic dissection.
PMID- 25133104
TI - Role of entry tear size in type B aortic dissection.
PMID- 25133105
TI - Best surgical option for arch extension of type B aortic dissection: the open
approach.
AB - Arch extension of aortic dissection (AD) is reported to occur in 4-25% of
patients presenting with acute type B AD. The DeBakey and Stanford
classifications do not specifically account for this subset, however, recent
studies have demonstrated that the prognosis of patients with arch extension in
acute type B AD is virtually identical to that of others with type B AD. In this
sense, it seems reasonable to extend the general management principles that are
applied to classic acute type B AD even to patients with arch extension. This may
be because even in patients with arch extension, most complications occur at
locations distal to the arch, and therefore treatment of these patients is
similar to that of complicated type B AD, namely thoracic endovascular aortic
repair (TEVAR). Conversely, 10% of patients with acute type B AD and arch
extension develop complications that are directly related to the arch pathology.
This clinical scenario generally necessitates surgical arch repair through a
sternotomy approach. The frozen elephant trunk technique combined with arch
repair is a very reasonable option to treat this unique clinical entity that
involves relatively distal locations of the aortic diseases. Combined arch and
descending aorta replacement through thoracotomy is an alternative option
particularly when the anatomical features of the target lesions are not suitable
for a sternotomy approach or TEVAR. Nonetheless, the reported mortality
associated with this approach has been exceedingly high. Hybrid arch repair is
another consideration in treating these patients to reduce the treatment-related
mortality and morbidity, especially when the arch pathology is limited to the
distal part. Nevertheless, the safety and efficacy of this procedure in cases
with more extensive arch involvement needs to be assessed in further studies in
comparison with other treatment modalities.
PMID- 25133106
TI - Medical management in type B aortic dissection.
AB - Medical management is generally the preferred treatment for uncomplicated type B
acute aortic dissection cases. It is often centered on the use of
antihypertensive agents, which alleviates hemodynamic stress on the damaged
aortic wall. Methods of medical management and drug selection are still based
mainly on personal experience, expert opinion and historical observational
studies as randomized controlled studies are lacking. Guidelines from European
(ESC), American (ACC/AHA) and Asian (Japan) societies in the last decade have
made recommendations on use of medications, but also reaffirmed the lack of
evidence for therapeutic approaches and targeted medical management. More recent
evidence suggests that there may be type-selective benefits for antihypertensive
medications. Here, we will discuss the present understanding of medical
management of acute aortic dissection.
PMID- 25133107
TI - Open fenestration for complicated acute aortic B dissection.
AB - Acute type B aortic dissection (ABAD) is a serious cardiovascular emergency in
which morbidity and mortality are often related to the presence of complications
at clinical presentation. Visceral, renal, and limb ischemia occur in up to 30%
of patients with ABAD and are associated with higher in-hospital mortality. The
aim of the open fenestration is to resolve the malperfusion by creating a single
aortic lumen at the suprarenal or infrarenal level. This surgical procedure is
less invasive than total aortic replacement, thus not requiring extracorporeal
support and allowing preservation of the intercostal arteries, which results in
decreased risk of paraplegia. Surgical aortic fenestration represents an
effective and durable option for treating ischemic complications of ABAD,
particularly for patients with no aortic dilatation. In the current endovascular
era, this open technique serves as an alternative option in case of
contraindications or failure of endovascular management of complicated ABAD.
PMID- 25133108
TI - TEVAR for complicated acute type B dissection with malperfusion.
PMID- 25133109
TI - Central cannulation (aortic and pulmonary artery) and sequential clamping from
distal to proximal in the surgical management of chronic type B dissection
utilizing hypothermic circulatory arrest.
PMID- 25133110
TI - Pitfalls in the hybrid approach of type B aortic dissection with arch
involvement.
PMID- 25133112
TI - Marfan syndrome.
PMID- 25133113
TI - Highlights from the 50th seminar of the korean society of gastrointestinal
endoscopy.
AB - The July issue of Clinical Endoscopy deals with selected articles covering the
state-of-the-art lectures delivered during the 50th seminar of the Korean Society
of Gastrointestinal Endoscopy (KSGE) on March 30, 2014, highlighting educational
contents pertaining to either diagnostic or therapeutic gastrointestinal (GI)
endoscopy, which contain fundamental and essential points in GI endoscopy. KSGE
is very proud of its seminar, which has been presented twice a year for the last
25 years, and hosted more than 3,500 participants at the current meeting. KSGE
seminar is positioned as one of premier state-of-the-art seminars for endoscopy,
covering topics for novice endoscopists and advanced experts, as well as
diagnostic and therapeutic endoscopy. The 50th KSGE seminar consists of more than
20 sessions, including a single special lecture, concurrent sessions for GI
endoscopy nurses, and sessions exploring new technologies. Nine articles were
selected from these prestigious lectures, and invited for publication in this
special issue. This introductory review, prepared by the editors of Clinical
Endoscopy, highlights core contents divided into four sessions: upper GI tract,
lower GI tract, pancreatobiliary system, and other specialized topic sessions,
including live demonstrations and hands-on courses.
PMID- 25133114
TI - Plastic and biodegradable stents for complex and refractory benign esophageal
strictures.
AB - Endoscopic stent placement is a well-accepted and effective alternative treatment
modality for complex and refractory esophageal strictures. Among the currently
available types of stents, the partially covered self-expanding metal stent
(SEMS) has a firm anchoring effect, preventing stent migration and ensuring
effective covering of a narrowed segment. However, hyperplastic tissue reaction
driven by the uncovered mesh may prevent easy and safe stent removal. As an
alternative, a fully covered SEMS decreases the recurrence of dysphagia caused by
hyperplastic tissue ingrowth; however, it has a high migration rate. Likewise,
although a self-expanding plastic stent (SEPS) reduces reactive hyperplasia, the
long-term outcome is disappointing because of the high rate of stent migration. A
biodegradable stent has the main benefit of not requiring stent removal in
comparison with SEMS and SEPS. However, it still has a somewhat high rate of
hyperplastic reaction, and the long-term outcome does not satisfy expectations.
Up to now, the question of which type of stent should be recommended for the
effective treatment of complex and refractory benign strictures has no clear
answer. Therefore, the selection of stent type for endoscopic treatment should be
individualized, taking into consideration the endoscopist's experience as well as
patient and stricture characteristics.
PMID- 25133115
TI - Evaluation and management of caustic injuries from ingestion of Acid or alkaline
substances.
AB - Although the numbers have decreased compared with in the past, cases of patients
who ingest caustic substances and visit the emergency room are not rare. However,
well-summarized data about caustic injuries are insufficient. Therefore, in this
article, I will discuss the etiologic causative agents, injury mechanism, and
clinical characteristics, as well as the endoscopic evaluation of the degree of
injury and proper management of the patient, in gastrointestinal caustic injury.
PMID- 25133116
TI - Management of acute variceal bleeding.
AB - Acute variceal bleeding could be a fatal complication in patients with liver
cirrhosis. In patients with decompensated liver cirrhosis accompanied by ascites
or hepatic encephalopathy, acute variceal bleeding is associated with a high
mortality rate. Therefore, timely endoscopic hemostasis and prevention of relapse
of bleeding are most important. The treatment goals for acute variceal bleeding
are to correct hypovolemia; achieve rapid hemostasis; and prevent early
rebleeding, complications related to bleeding, and deterioration of liver
function. If variceal bleeding is suspected, treatment with vasopressors and
antibiotics should be initiated immediately on arrival to the hospital.
Furthermore, to obtain hemodynamic stability, the hemoglobin level should be
maintained at >8 g/dL, systolic blood pressure >90 to 100 mm Hg, heart rate
<100/min, and the central venous pressure from 1 to 5 mm Hg. When the patient
becomes hemodynamically stable, hemostasis should be achieved by performing
endoscopy as soon as possible. For esophageal variceal bleeding, endoscopic
variceal ligation is usually performed, and for gastric variceal bleeding,
endoscopic variceal obturation is performed primarily. If it is considered
difficult to achieve hemostasis through endoscopy, salvage therapy may be carried
out while keeping the patient hemodynamically stable.
PMID- 25133117
TI - Endoscopy for nonvariceal upper gastrointestinal bleeding.
AB - Endoscopy for acute nonvariceal upper gastrointestinal bleeding plays an
important role in primary diagnosis and management, particularly with respect to
identification of high-risk stigmata lesions and to providing endoscopic
hemostasis to reduce the risk of rebleeding and mortality. Early endoscopy,
defined as endoscopy within the first 24 hours after presentation, improves
patient outcome and reduces the length of hospitalization when compared with
delayed endoscopy. Various endoscopic hemostatic methods are available, including
injection therapy, mechanical therapy, and thermal coagulation. Either single
treatment with mechanical or thermal therapy or a treatment that combines more
than one type of therapy are effective and safe for peptic ulcer bleeding. Newly
developed methods, such as Hemospray powder and over-the-scope clips, may provide
additional options. Appropriate decisions and specific treatment are needed
depending upon the conditions.
PMID- 25133118
TI - Management of Antithrombotic Therapy for Gastroenterological Endoscopy from a
Cardio-Cerebrovascular Physician's Point of View.
AB - Periprocedural management of antithrombotics for gastroenterological endoscopy is
a common clinical issue. To decide how to manage the use of antithrombotics in
patients undergoing endoscopy, the risk for hemorrhage and thromboembolism during
the procedure must be considered. For low-risk procedures, no adjustments in
antithrombotics are needed. For high-risk procedures with a low thromboembolic
risk, discontinuation of warfarin at 5 days, and clopidogrel at 5 to 7 days
before the procedure has been recommended. However, it is better to continue
aspirin use even during high-risk procedures. A heparin bridging therapy may be
considered before endoscopy in patients with a high thromboembolic risk. The
management of patients taking antithrombotics remains complex, especially in high
risk settings.
PMID- 25133119
TI - Prerequisites of colonoscopy.
AB - Colonoscopy is a widely accepted method for the evaluation of the colon and
terminal ileum. Its diagnostic accuracy and therapeutic safety are influenced by
prerequisites, including modulation of medication and bowel cleansing.
Appropriate choices of sedative medication and bowel-cleansing regimen, together
with diet modification, should be made based on the patient's underlying disease,
age, and medication intake. Moreover, effective methods for patient education
regarding bowel preparation should be considered.
PMID- 25133120
TI - Equipment-based image-enhanced endoscopy for differentiating colorectal polyps.
AB - The use of colonoscopy for the screening and surveillance of colorectal cancer
has increased. However, the miss rate of advanced colorectal neoplasm is known to
be 2% to 6%, which could be affected by the image intensity of colorectal
lesions. Image-enhanced endoscopy (IEE) is capable of highlighting lesions, which
can improve the colorectal adenoma detection rate and diagnostic accuracy.
Equipment-based IEE methods, such as narrow band imaging (NBI), Fujinon
intelligent color enhancement (FICE), and i-Scan, are used to observe the mucosal
epithelium of the microstructure and capillaries of the lesion, and are helpful
in the detection and differential diagnosis of colorectal tumors. Although NBI is
similar to chromoendoscopy in terms of adenoma detection rates, NBI can be used
to differentiate colorectal polyps and to predict the submucosal invasion of
malignant tumors. It is also known that FICE and i-Scan are similar to NBI in
their detection rates of colorectal lesions. Through more effective and advanced
endoscopic equipment, diagnostic accuracy could be improved and new treatment
paradigms developed.
PMID- 25133121
TI - Preparation of high-risk patients and the choice of guidewire for a successful
endoscopic retrograde cholangiopancreatography procedure.
AB - Endoscopic retrograde cholangiopancreatography (ERCP) is an essential technique
for the diagnosis and treatment of pancreatobiliary diseases. However, ERCP
related complications such as pancreatitis, cholangitis, hemorrhage, and
perforation may be problematic. For a successful and safe ERCP, preprocedural
evaluations of the patients and intervention-related risk factors are needed.
Furthermore, in light of the recent population aging and increase in chronic
cardiopulmonary diseases in Korea, precautions including endoscopic sedation and
prevention of cardiopulmonary complications should be considered. In this
literature review, we describe these risk factors and the use of endoscopic
sedation. In addition, we reviewed the commonly available guidewires, including
their materials and options, used as a basic accessory for ERCP procedures.
PMID- 25133122
TI - The management of endoscopic retrograde cholangiopancreatography-related duodenal
perforation.
AB - Uneventful duodenal perforation during endoscopic retrograde
cholangiopancreatography (ERCP) is an uncommon but occasionally fatal
complication. ERCP-related perforations may occur during sphincterotomy and
improper manipulation of the equipment and scope. Traditionally, duodenal
perforation has been treated with early surgical repair. Recently, nonoperative
early endoscopic management techniques including clips or fibrin glue have been
reported. In the present paper we review the literature pertaining to the
treatment of perforations.
PMID- 25133123
TI - A case report of primary duodenal tuberculosis mimicking a malignant tumor.
AB - Tuberculosis remains a serious infectious disease with primary features of
pulmonary manifestation in Korea. However, duodenal tuberculosis is rare in
gastrointestinal cases of extrapulmonary tuberculosis. Here, we report a case of
primary duodenal tuberculosis mistaken as a malignant tumor and diagnosed with
QuantiFERON-TB GOLD (Cellestis Ltd.) in an immunocompetent male patient.
PMID- 25133124
TI - Primary papillary thyroid carcinoma diagnosed by using endoscopic ultrasound with
fine needle aspiration.
AB - There is paucity in the literature on the use of endoscopic ultrasound (EUS) for
evaluating the thyroid gland. We report the first case of primary papillary
thyroid cancer diagnosed by using EUS and fine needle aspiration (FNA). A 66-year
old man underwent EUS for the evaluation of mediastinal lymphadenopathy. FNA of
the lymph nodes showed benign findings. A hypoechoic mass was noted in the right
lobe of the thyroid gland. Therefore, FNA was performed. The cytological results
were consistent with primary papillary thyroid cancer.
PMID- 25133125
TI - A case of endoscopic full-thickness resection in a patient with gastric high
grade dysplasia unsuitable for endoscopic submucosal dissection.
AB - Gastric high-grade dysplasia is an important premalignant lesion in gastric
epithelial cells and has a high possibility of transforming to adenocarcinoma.
Therefore, biopsy-proven high-grade dysplasia should be treated with en bloc
resection methods such as endoscopic mucosal resection or endoscopic submucosal
dissection (ESD). We report the case of a 63-year-old male patient, diagnosed
with gastric high-grade dysplasia at the angle and lesser curvature side of the
lower body. The patient was initially treated with ESD, although histopathology
subsequently showed horizontal margin involvement. Since the lesion was diffusely
edematous and margins were uncertain because of the previous ESD treatment, we
chose to treat the patient with laparoscopy-assisted endoscopic full-thickness
resection (EFTR). EFTR is a recently developed procedure, which uses both
endoscopic and laparoscopic techniques to resect the full-thickness of the
tissue. The final pathologic report revealed high-grade dysplasia and a focal
intramucosal carcinoma of 0.8*0.7 cm. We conclude that EFTR can be an effective
alternative treatment in gastric high-grade dysplasia unsuitable for ESD.
PMID- 25133126
TI - Xanthoma of the esophagus.
AB - Xanthoma is an uncommon nonneoplastic lesion resulting from the accumulation of
histiocytes. It predominantly shows cutaneous manifestations associated with
dyslipidemia. However, xanthoma of the esophagus is extremely rare. To the best
of our knowledge, only 14 cases have been reported thus far. The clinical
significance of this lesion has not been established. However, this lesion should
be distinguished grossly from ectopic sebaceous glands and small subepithelial
tumors such as carcinoid and granular cell tumor. Moreover, signet ring cell
carcinoma, which contains round cells with abundant cytoplasm and has similar
histologic features to xanthoma, should be distinguished microscopically.
PMID- 25133127
TI - Endoscopic Management of Rectal Dieulafoy's Lesion: A Case Series and Optimal
Treatment.
AB - Rectal Dieulafoy's lesion (DL) is rare cause of lower gastrointestinal bleeding.
Because of its rarity, there is no consensus on the optimal endoscopic hemostasis
technique for rectal DL. We analyzed six patients who underwent endoscopic
management for rectal DL after presenting with hematochezia at a single institute
over 10 years. Of the six patients, three underwent endoscopic band ligation
(EBL) and three underwent endoscopic hemoclip placement (EHP). Only one patient
was treated with thermocoagulation. There were no immediate complications in any
of the patients. None of the patients required a procedure or surgery for the
treatment of rebleeding. Mean procedure times of EBL and EHP were 5.25 minutes
and 7 minutes, respectively. Both EHP and EBL are shown to be effective in the
treatment of bleeding rectal DL. We suggest that EBL may have potential as the
preferred therapy owing to its superiority in technical and economic aspects,
especially in elderly and high-risk patients.
PMID- 25133129
TI - Reader's Forum.
PMID- 25133128
TI - Electrohydraulic lithotripsy of an impacted enterolith causing acute afferent
loop syndrome.
AB - Afferent loop syndrome caused by an impacted enterolith is very rare, and
endoscopic removal of the enterolith may be difficult if a stricture is present
or the normal anatomy has been altered. Electrohydraulic lithotripsy is commonly
used for endoscopic fragmentation of biliary and pancreatic duct stones. A 64
year-old man who had undergone subtotal gastrectomy and gastrojejunostomy
presented with acute, severe abdominal pain for a duration of 2 hours. Initially,
he was diagnosed with acute pancreatitis because of an elevated amylase level and
pain, but was finally diagnosed with acute afferent loop syndrome when an
impacted enterolith was identified by computed tomography. We successfully
removed the enterolith using direct electrohydraulic lithotripsy conducted using
a transparent cap-fitted endoscope without complications. We found that this
procedure was therapeutically beneficial.
PMID- 25133130
TI - Comparison of frictional forces between aesthetic orthodontic coated wires and
self-ligation brackets.
AB - OBJECTIVE: The purpose of this study was to evaluate the clinical efficacy of
polymer- and rhodium-coated wires compared to uncoated wires by measuring the
frictional forces using self-ligation brackets. METHODS: 0.016-inch nickel
titanium (NiTi) wires and 0.017 * 0.025-inch stainless steel (SS) wires were
used, and the angulations between the brackets and wires were set to 0 degrees ,
5 degrees , and 10 degrees . Upper maxillary premolar brackets (Clippy-C(r)) with
a 0.022-inch slot were selected for the study and a tensile test was performed
with a crosshead speed of 5 mm/min. The maximum static frictional forces and
kinetic frictional forces were recorded and compared. RESULTS: The maximum static
frictional forces and the kinetic frictional forces of coated wires were equal to
or higher than those of the uncoated wires (p < 0.05). The maximum static
frictional forces of rhodium-coated wires were significantly higher than those of
polymer-coated wires when the angulations between the brackets and wires were set
to (i) 5 degrees in the 0.016-inch NiTi wires and (ii) all angulations in the
0.017 * 0.025-inch SS wires (p < 0.05). The kinetic frictional forces of rhodium
coated wires were higher than those of polymer-coated wires, except when the
angulations were set to 0 degrees in the 0.016-inch NiTi wires (p < 0.05).
CONCLUSIONS: Although the frictional forces of the coated wires with regards to
aesthetics were equal to or greater than those of the uncoated wires, a study
under similar conditions regarding the oral cavity is needed in order to
establish the clinical implications.
PMID- 25133131
TI - Randomized controlled clinical trial of oral health-related quality of life in
patients wearing conventional and self-ligating brackets.
AB - OBJECTIVE: The aim of this randomized controlled clinical trial was to compare
oral health-related quality of life (OHRQoL) of patients treated with
conventional, active self-ligating (ASL), and passive self-ligating (PSL)
brackets in different therapeutic phases. METHODS: Sixty patients (mean age 18.3
years; 29 males and 31 females) requiring orthodontic treatment were randomly and
equally assigned to receive conventional (Victory Series), ASL (In-Ovation R), or
PSL (Damon 3MX) brackets. OHRQoL was measured with a self-administered modified
16-item Malaysian version of the Oral Health Impact Profile for immediate (soon
after the visit) and late (just before the subsequent visit) assessments of the
bonding and activation phases. Data were analyzed with the Kruskal-Wallis and chi
square tests. RESULTS: The PSL and ASL groups showed more immediate and late
impacts in the bonding phase, respectively; the conventional group was affected
in both the assessments. The first activation phase had similar impacts in the
groups. After the second activation, the conventional group showed more immediate
impacts, whereas the PSL and ASL groups had more late impacts. The commonly
affected domains were "physical disability," "functional limitation," "physical
pain," and "psychological discomfort." No significant differences in the
prevalence and severity of immediate and late impacts on OHRQoL of the patients
were noted in any therapeutic phase. CONCLUSIONS: No bracket system seems to
ensure superior OHRQoL. This information could be useful for explaining the
therapeutic phases, especially the initial one, and selecting the optimal bracket
system based on the patient's preference.
PMID- 25133132
TI - Geometrical design characteristics of orthodontic mini-implants predicting
maximum insertion torque.
AB - OBJECTIVE: To determine the unique contribution of geometrical design
characteristics of orthodontic mini-implants on maximum insertion torque while
controlling for the influence of cortical bone thickness. METHODS: Total number
of 100 cylindrical orthodontic mini-implants was used. Geometrical design
characteristics of ten specimens of ten types of cylindrical self-drilling
orthodontic mini-implants (Ortho Easy(r), Aarhus, and Dual TopTM) with diameters
ranging from 1.4 to 2.0 mm and lengths of 6 and 8 mm were measured. Maximum
insertion torque was recorded during manual insertion of mini-implants into bone
samples. Cortical bone thickness was measured. Retrieved data were analyzed in a
multiple regression model. RESULTS: Significant predictors for higher maximum
insertion torque included larger outer diameter of implant, higher lead angle of
thread, and thicker cortical bone, and their unique contribution to maximum
insertion torque was 12.3%, 10.7%, and 24.7%, respectively. CONCLUSIONS: The
maximum insertion torque values are best controlled by choosing an implant
diameter and lead angle according to the assessed thickness of cortical bone.
PMID- 25133133
TI - Facial profile parameters and their relative influence on bilabial prominence and
the perceptions of facial profile attractiveness: A novel approach.
AB - OBJECTIVE: To evaluate the relative importance of bilabial prominence in relation
to other facial profile parameters in a normal population. METHODS: Profile
stimulus images of 38 individuals (28 female and 10 male; ages 19-25 years) were
shown to an unrelated group of first-year students (n = 42; ages 18-24 years).
The images were individually viewed on a 17-inch monitor. The observers received
standardized instructions before viewing. A six-question questionnaire was
completed using a Likert-type scale. The responses were analyzed by ordered
logistic regression to identify associations between profile characteristics and
observer preferences. The Bayesian Information Criterion was used to select
variables that explained observer preferences most accurately. RESULTS: Nasal,
bilabial, and chin prominences; the nasofrontal angle; and lip curls had the
greatest effect on overall profile attractiveness perceptions. The lip-chin
throat angle and upper lip curl had the greatest effect on forehead prominence
perceptions. The bilabial prominence, nasolabial angle (particularly the lower
component), and mentolabial angle had the greatest effect on nasal prominence
perceptions. The bilabial prominence, nasolabial angle, chin prominence, and
submental length had the greatest effect on lip prominence perceptions. The
bilabial prominence, nasolabial angle, mentolabial angle, and submental length
had the greatest effect on chin prominence perceptions. CONCLUSIONS: More
prominent lips, within normal limits, may be considered more attractive in the
profile view. Profile parameters have a greater influence on their neighboring
aesthetic units but indirectly influence related profile parameters, endorsing
the importance of achieving an aesthetic balance between relative prominences of
all aesthetic units of the facial profile.
PMID- 25133134
TI - Modification of surface pretreatment of white spot lesions to improve the safety
and efficacy of resin infiltration.
AB - OBJECTIVE: A low-viscosity resin (infiltrant) was used to inhibit the progression
of white spot lesions (WSLs) and resolve associated esthetic issues. An
alternative pretreatment was explored to increase the pore volume of the surface
layer of the WSLs. Also, the penetration effects of the infiltrant were evaluated
for various pretreatments. METHODS: Sixty two artificial lesions were fabricated
on bovine teeth. As a positive control, 15% HCl gel was applied for 120 seconds.
Further, 37% H3PO4 gel was applied for 30 seconds using three methods. The
samples were divided as follows: H3PO4 only group, H3PO4 sponge group, and H3PO4
brush group. The acid was gently rubbed with the applicators (i.e., a sponge or
brush) throughout the application time. To compare the effects of resin
infiltration, twenty paired halves of specimens were treated with an infiltrant
(ICON(r)). RESULTS: Thicknesses of the removed surface layers and infiltrated
areas were evaluated by confocal laser scanning microscope. The positive control
and the 37% H3PO4 brush group failed to show significant differences in the
removed thickness (p > 0.05); however, the mean percentage of the infiltrated
area was higher in the 37% H3PO4 brush group (84.13 +/- 7.58%) than the positive
control (63.51 +/- 7.62%, p < 0.001). Scanning electron microscope observations
indicate higher pore volumes for the 37% H3PO4 brush group than for the positive
control. CONCLUSIONS: Application of 37% H3PO4 with a brush for 30 seconds
increased the pore volume of WSL surface layers and the percentage of infiltrated
areas in comparison to the use of 15% HCl for 120 seconds.
PMID- 25133135
TI - Treatment and retention of relapsed anterior open-bite with low tongue posture
and tongue-tie: A 10-year follow-up.
AB - The purpose of the current report is to present 6-year long-term stability and 10
year follow-up data for an adult patient who was treated with a tongue elevator
for relapsed anterior open-bite. The 19-year-old male patient presented with the
chief complaint of difficulty in chewing his food. Collectively, clinical and
radiographic examinations revealed an anterior open-bite, low tongue posture, and
tongue-tie. The patient opted for orthodontic treatment alone, without any
surgical procedure. A lingual frenectomy was recommended to avoid the risk of
relapse, but the patient declined because he was not experiencing tongue
discomfort. Initial treatment of the anterior open-bite with molar intrusion and
tongue exercises was successful, but relapse occurred during the retention
period. A tongue elevator was used for retreatment, because the approach was
minimally invasive and suited the patient's requirements regarding discomfort,
cost, and time. The appliance changed the tongue posture and generated an altered
tongue force, which ultimately resulted in intrusive dentoalveolar effects, and a
subsequent counterclockwise rotation of the mandible. The results showed long
term stability and were maintained for six years through continual use of the
tongue elevator. The results of this case indicated that a tongue elevator could
be used not only as an alternative treatment for open-bite, but also as an active
retainer.
PMID- 25133136
TI - Interdisciplinary rehabilitation of a root-fractured maxillary central incisor: A
12-year follow-up case report.
AB - Single-tooth implantation has become a common treatment solution for replacement
of a root-fractured maxillary incisor in adults, but the long-term esthetic
results can be unfavorable due to progressive marginal bone loss, resulting in
gingival recession. In this case report, a maxillary central incisor with a root
fracture in its apical one-third was orthodontically extruded and extracted in a
21-year-old female. Implant surgery was performed after a 3-month healing period,
and the final crown was placed about 12 months after extraction. After 12 years,
favorable osseous and gingival architectures were visible with adequate bone
height and thickness at the buccal cortical plate, and no gingival recession was
seen around the implant-supported crown. Although modern dentistry has been
shifting toward simplified, clinical procedures and shorter treatment times, both
general dentists and orthodontists should be aware of the possible long-term
esthetic advantages of orthodontic extrusion of hopelessly fractured teeth for
highly esthetically demanding areas and should educate and motivate patients
regarding the choice of this treatment solution, if necessary.
PMID- 25133138
TI - Secondhand Smoke Exposure and Severity of Attention-Deficit/Hyperactivity
Disorder in Preschoolers: A Pilot Investigation.
AB - BACKGROUND: Less is known about the effects of secondhand smoke (SHS) on mental
health as compared with other medical disorders. OBJECTIVE: The aims of this
study were to examine the following: 1) the association of SHS exposure with
childhood attention-deficit/hyperactivity (ADHD) and disruptive disorders; and 2)
the association of maternal recall of a child's SHS exposure and that child's
exposure as measured by bioassay. METHOD: Sixty children had their saliva
collected and assayed for cotinine when they were 4 years old and again when they
were 6 years old. Phone interview data were collected to assess maternal recall
of the children's exposure to SHS at these ages. The children were assessed
annually for ADHD and disruptive disorders. Repeated measures analysis of
exposure level by child characteristics was performed. RESULTS: Greater ADHD and
conduct disorder severity scores were associated with greater child smoke
exposure (ADHD severity, P = .043; conduct disorder severity, P = .035). A large
proportion of mothers reported that their children had no exposure to SHS,
despite high levels of measured cotinine in the children's saliva. CONCLUSIONS:
An association between SHS exposure and ADHD and conduct disorder symptoms was
found. Children and parents may benefit from parent education regarding the
deleterious effects of SHS.
PMID- 25133137
TI - Dielectrophoretic capture and genetic analysis of single neuroblastoma tumor
cells.
AB - Our understanding of the diversity of cells that escape the primary tumor and
seed micrometastases remains rudimentary, and approaches for studying circulating
and disseminated tumor cells have been limited by low throughput and sensitivity,
reliance on single parameter sorting, and a focus on enumeration rather than
phenotypic and genetic characterization. Here, we utilize a highly sensitive
microfluidic and dielectrophoretic approach for the isolation and genetic
analysis of individual tumor cells. We employed fluorescence labeling to isolate
208 single cells from spiking experiments conducted with 11 cell lines, including
8 neuroblastoma cell lines, and achieved a capture sensitivity of 1 tumor cell
per 10(6) white blood cells (WBCs). Sample fixation or freezing had no detectable
effect on cell capture. Point mutations were accurately detected in the whole
genome amplification product of captured single tumor cells but not in negative
control WBCs. We applied this approach to capture 144 single tumor cells from 10
bone marrow samples of patients suffering from neuroblastoma. In this pediatric
malignancy, high-risk patients often exhibit wide-spread hematogenous metastasis,
but access to primary tumor can be difficult or impossible. Here, we used flow
based sorting to pre-enrich samples with tumor involvement below 0.02%. For all
patients for whom a mutation in the Anaplastic Lymphoma Kinase gene had already
been detected in their primary tumor, the same mutation was detected in single
cells from their marrow. These findings demonstrate a novel, non-invasive, and
adaptable method for the capture and genetic analysis of single tumor cells from
cancer patients.
PMID- 25133139
TI - Current Perspectives on Viable but Non-Culturable (VBNC) Pathogenic Bacteria.
AB - Under stress conditions, many species of bacteria enter into starvation mode of
metabolism or a physiologically viable but non-culturable (VBNC) state. Several
human pathogenic bacteria have been reported to enter into the VBNC state under
these conditions. The pathogenic VBNC bacteria cannot be grown using conventional
culture media, although they continue to retain their viability and express their
virulence. Though there have been debates on the VBNC concept in the past,
several molecular studies have shown that not only can the VBNC state be induced
under in vitro conditions but also that resuscitation from this state is possible
under appropriate conditions. The most notable advance in resuscitating VBNC
bacteria is the discovery of resuscitation-promoting factor (Rpf), which is a
bacterial cytokines found in both Gram-positive and Gram-negative organisms. VBNC
state is a survival strategy adopted by the bacteria, which has important
implication in several fields, including environmental monitoring, food
technology, and infectious disease management; and hence it is important to
investigate the association of bacterial pathogens under VBNC state and the
water/foodborne outbreaks. In this review, we describe various aspects of VBNC
bacteria, which include their proteomic and genetic profiles under the VBNC
state, conditions of resuscitation, methods of detection, antibiotic resistance,
and observations on Rpf.
PMID- 25133142
TI - Dissociative symptoms and dissociative disorders comorbidity in obsessive
compulsive disorder: Symptom screening, diagnostic tools and reflections on
treatment.
AB - Borderline personality disorder, conversion disorder and obsessive compulsive
disorder frequently have dissociative symptoms. The literature has demonstrated
that the level of dissociation might be correlated with the severity of obsessive
compulsive disorder (OCD) and that those not responding to treatment had high
dissociative symptoms. The structured clinical interview for DSM-IV dissociative
disorders, dissociation questionnaire, somatoform dissociation questionnaire and
dissociative experiences scale can be used for screening dissociative symptoms
and detecting dissociative disorders in patients with OCD. However, a history of
neglect and abuse during childhood is linked to a risk factor in the pathogenesis
of dissociative psychopathology in adults. The childhood trauma questionnaire-53
and childhood trauma questionnaire-40 can be used for this purpose. Clinicians
should not fail to notice the hidden dissociative symptoms and childhood
traumatic experiences in OCD cases with severe symptoms that are resistant to
treatment. Symptom screening and diagnostic tools used for this purpose should be
known. Knowing how to treat these pathologies in patients who are diagnosed with
OCD can be crucial.
PMID- 25133141
TI - Progress in sensorimotor rehabilitative physical therapy programs for stroke
patients.
AB - Impaired motor and functional activity following stroke often has negative
impacts on the patient, the family and society. The available rehabilitation
programs for stroke patients are reviewed. Conventional rehabilitation strategies
(Bobath, Brunnstrom, proprioception neuromuscular facilitation, motor relearning
and function-based principles) are the mainstream tactics in clinical practices.
Numerous advanced strategies for sensory-motor functional enhancement, including
electrical stimulation, electromyographic biofeedback, constraint-induced
movement therapy, robotics-aided systems, virtual reality, intermittent
compression, partial body weight supported treadmill training and thermal
stimulation, are being developed and incorporated into conventional
rehabilitation programs. The concept of combining valuable rehabilitative
procedures into "a training package", based on the patient's functional status
during different recovery phases after stroke is proposed. Integrated
sensorimotor rehabilitation programs with appropriate temporal arrangements might
provide great functional benefits for stroke patients.
PMID- 25133143
TI - Metabolic syndrome and childhood trauma: Also comorbidity and complication in
mood disorder.
AB - Studies for prevalence and causal relationship established that addressing
comorbidities of mental illnesses with medical disease will be another revolution
in psychiatry. Increasing number of evidence shows that there is a bidirectional
connection between mood disorders and some medical diseases.
Glucocorticoid/insulin signal mechanisms and immunoenflammatory effector systems
are junction points that show pathophysiology between bipolar disorder and
general medical situations susceptible to stress. A subgroup of mood disorder
patients are under risk of developing obesity and diabetes. Their habits and life
styles, genetic predisposition and treatment options are parameters that define
this subgroup. Medical disease in adults had a significant relationship to
adverse life experiences in childhood. This illustrates that adverse experiences
in childhood are related to adult disease by two basic etiologic mechanisms: (1)
conventional risk factors that actually are compensatory behaviors, attempts at
self-help through the use of agents and foods; and (2) the effects of chronic
stress.
PMID- 25133140
TI - Psychosocial perspectives and the issue of prevention in childhood obesity.
AB - A dramatic increase in childhood overweight/obesity has been recognized globally
over the past 50 years. This observed increase may reflect genetic, as well as
psychological, environmental, and socio-cultural influences. In the first part of
this review, we present an updated summary of the psychosocial factors associated
with this change and discuss possible ways in which they operate. Among these
factors, lower socio economic status (in both industrialized and non
industrialized countries), being female, belonging to a minority group, and being
exposed to adverse life events may all be associated with a greater risk of
childhood overweight/obesity. These influences may be mediated via a variety of
mechanisms, in particular above-average food intake of low nutritional quality
and reduction in physical activity. Other important psychosocial mediators
include the influence of the family and peer environment, and exposure to the
media. In the second part of the review, we discuss the potential of psychosocial
prevention programs to intervene in the processes involved in the rise of
childhood overweight/obesity. Two points are emphasized. First, prevention
programs should be multidisciplinary, combining the knowledge of experts from
different professions, and taking into consideration the important role of the
family environment and relevant influential social organizations, particularly
school. Second, effective change is unlikely to occur without large-scale
programs carried out on a public policy level.
PMID- 25133144
TI - Pseudocyesis, delusional pregnancy, and psychosis: The birth of a delusion.
AB - Both pseudocyesis and delusional pregnancy are said to be rare syndromes, but are
reported frequently in developing countries. A distinction has been made between
the two syndromes, but the line of demarcation is blurred. The aim of this paper
is to review recent cases of pseudocyesis/delusional pregnancy in order to learn
more about biopsychosocial antecedents. The recent world literature (2000-2014)
on this subject (women only) was reviewed, making no distinction between
pseudocyesis and delusional pregnancy. Eighty case histories were found, most of
them originating in developing countries. Fifty patients had been given a
diagnosis of psychosis, although criteria for making the diagnosis were not
always clear. The psychological antecedents included ambivalence about pregnancy,
relationship issues, and loss. Very frequently, pseudocyesis/delusional pregnancy
occurred when a married couple was infertile and living in a pronatalist society.
The infertility was attributed to the woman, which resulted in her experiencing
substantial distress and discrimination. When antipsychotic medication was used
to treat psychotic symptoms in these women, it led to high prolactin levels and
apparent manifestations of pregnancy, such as amenorrhea and galactorrhea, thus
reinforcing a false conviction of pregnancy. Developing the erroneous belief that
one is pregnant is an understandable process, making the delusion of pregnancy a
useful template against which to study the evolution of other, less explicable
delusions.
PMID- 25133145
TI - Tree stand falls: A persistent cause of neurological injury in hunting.
AB - AIM: To characterize and compare our current series of patients to prior reports
in order to identify any changes in the incidence of neurological injury related
to hunting accidents in Rochester, New York. METHODS: All tree stand-related
injuries referred to our regional trauma center from September 2003 through
November 2011 were reviewed. Information was obtained from the hospital's trauma
registry and medical records were retrospectively reviewed for data pertaining to
the injuries. RESULTS: Fifty-four patients were identified. Ninety-six percent of
patients were male with a mean age of 47.9 years (range 15-69). The mean Injury
Severity Score was 12.53 +/- 1.17 (range 2-34). The average height of fall was
18.2 feet (range 4-40 feet). All patients fell to the ground with the exception
of one who landed on rocks, and many hit the tree or branches on the way down. A
reason for the fall was documented in only 13 patients, and included tree stand
construction (3), loss of balance (3), falling asleep (3), structural failure
(2), safety harness breakage (3) or light-headedness (1). The most common
injuries were spinal fractures (54%), most commonly in the cervical spine (69%),
followed by the thoracic (38%) and lumbar (21%) spine. Eight patients required
operative repair. Head injuries occurred in 22%. Other systemic injuries include
rib/clavicular fractures (47%), pelvic fractures (11%), solid organ injury (23%),
and pneumothorax or hemothorax (19%). No patient deaths were reported. The
average hospital length of stay was 6.56 +/- 1.07 d. Most patients were
discharged home without (72%) or with (11%) services and 17% required
rehabilitation. CONCLUSION: Falls from hunting tree stands are still common, with
a high rate of neurological injury. Compared to a decade ago we have made no
progress in preventing these neurological injuries, despite an increase in safety
advances. Neurosurgeons must continue to advocate for increased safety awareness
and participate in leadership roles to improve outcomes for hunters.
PMID- 25133146
TI - Intracerebroventricular opiate infusion for refractory head and facial pain.
AB - AIM: To study the risks and benefits of intracerebroventricular (ICV) opiate
pumps for the management of benign head and face pain. METHODS: SSix patients
with refractory trigeminal neuralgia and/or cluster headaches were evaluated for
implantation of an ICV opiate infusion pump using either ICV injections through
an Ommaya reservoir or external ventricular drain. Four patients received
morphine ICV pumps and two patientS received a hydromorphone pump. Of the Four
patients with morphine ICV pumps, one patient had the medication changed to
hydromorphone. Preoperative and post-operative visual analog scores (VAS) were
obtained. Patients were evaluated post-operatively for a minimum of 3 mo and the
pump dosage was adjusted at each outpatient clinic visit according to the
patient's pain level. RESULTS: All 6 patients had an intracerebroventricular
opiate injection trial period, using either an Ommaya reservoir or an external
ventricular drain. There was an average VAS improvement of 75.8%. During the
trial period, no complications were observed. Pump implantation was performed an
average of 3.7 wk (range 1-7) after the trial injections. After implantation, an
average of 20.7 +/- 8.3 dose adjustments were made over 3-56 mo after surgery to
achieve maximal pain relief. At the most recent follow-up (26.2 mo, range 3-56),
VAS scores significantly improved from an average of 7.8 +/- 0.5 (range 6-10) to
2.8 +/- 0.7 (range 0-5) at the final dose (mean improvement 5.0 +/- 1.0, P <
0.001). All patients required a stepwise increase in opiate infusion rates to
achieve maximal benefit. The most common complications were nausea and
drowsiness, both of which resolved with pump adjustments. On average, infusion
pumps were replaced every 4-5 years. CONCLUSION: These results suggest that ICV
delivery of opiates may potentially be a viable treatment option for patients
with intractable pain from trigeminal neuralgia or cluster headache.
PMID- 25133147
TI - Distal biceps tendon rupture reconstruction using muscle-splitting double
incision approach.
AB - AIM: To evaluate the clinical and functional results after repair of distal
biceps tendon tears, following the Morrey's modified double-incision approach.
METHODS: We retrospectively reviewed 47 patients with distal rupture of biceps
brachii treated between 2003 and 2012 in our Orthopedic Department with muscle
splitting double-incision technique. Outcome measures included the Mayo elbow
performance, the DASH questionnaire, patient's satisfaction, elbow and forearm
motion, grip strength and complications occurrence. RESULTS: At an average 18 mo
follow-up (range, 7 mo-10 years) the average Mayo elbow performance and DASH
score were respectively 97.2 and 4.8. The elbow flexion range was 94%, extension
was -2 degrees , supination was 93% and pronation 96% compared with the uninjured
limb. The mean grip strength, expressed as percentage of respective contralateral
limb, was 83%. The average patient satisfaction rating on a Likert scale (from 0
to 10) was 9.4. The following complications were observed: 3 cases of heterotopic
ossification (6.4%), one (2.1%) re-rupture of the tendon at the site of
reattachment and 2 cases (4.3%) of posterior interosseous nerve palsy. No
complication required further surgical treatment. CONCLUSION: This technique
allows an anatomic reattachment of distal biceps tendon at the radial tuberosity
providing full functional recovery with low complication rate.
PMID- 25133148
TI - Dabigatran etixilate and traumatic brain injury: Evolving anticoagulants require
evolving care plans.
AB - AIM: To investigate the outcomes of trauma patients with traumatic brain injury
(TBI) on Dabigatran Etexilate (DE). METHODS: Following IRB approval, all patients
taking DE who were admitted to our level 1 trauma service were enrolled in the
study. Injury complexity, length of stay (LOS), intensive care length of stay,
operative intervention, therapeutic interventions and outcomes were analyzed
retrospectively. RESULTS: Twenty-eight of 4310 admissions were taking DE. Eleven
patients were excluded on concurrent antiplatelet therapy. Average age was 77.14
years (64-94 years), and average LOS was 4.7 d (1-35 d). Thirty-two percent were
admitted with intracranial hemorrhage. Eighteen percent received factor VII, and
22% received dialysis in attempts to correct coagulopathy. Mortality was 21%.
CONCLUSION: The low incidence, absence of reversal agents, and lack of practice
guidelines makes managing patients with TBI taking DE frustrating and provider
specific. Local practice guidelines may be helpful in managing such patients.
PMID- 25133149
TI - Desmoplastic small round cell tumor with atypical immunohistochemical profile and
rhabdoid-like differentiation.
AB - Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive malignant
neoplasm of unknown origin, and is comprised of small round cells with a
characteristic desmoplastic stroma. DSRCT typically expresses epithelial,
mesenchymal and neural markers simultaneously. We describe a case of DSRCT with
an atypical immunohistochemical profile and rhabdoid-like tumor cells on electron
microscopy. In the present case, the neoplastic cells were positive only for
vimentin, desmin (cytoplasmic membranous pattern) and CD56, and negative for
smooth muscle actin, synaptophysin, CD117, CD45, myogenin, CAM5.2,
pancytokeratin, WT1, EMA, CD99, neurofilament, CD34 and p53. Ki67 showed a low
proliferative activity. Electron microscopy showed focal rhabdoid
differentiation. However, INI-1 (SNF-5/BAF47) demonstrated preservation of
nuclear positivity in the neoplastic cells. Cytogenetic studies showed
translocation t(11;22)(p13;q12) confirming an EWSR1-WT1 translocation
characteristic for DSRCT, and t(1;15)(q11;p11.2) of unknown significance. This
case is a diagnostic challenge because of atypical immunohistochemical profile
and cytogenetic study is crucial in rendering the correct diagnosis.
PMID- 25133150
TI - Resolution of hemolysis from pump thrombus during left ventricular assist device
exchange.
AB - A 50-year-old male who underwent a HeartMate II left ventricular assist device
placement for ischemic cardiomyopathy presented with discolored urine and
hemolysis 3 mo after the operation. His hemolysis was thought to be due to
thrombosis within the pump. Imaging studies were not able to visualize a left
ventricular thrombus. Medical management with anticoagulation failed and he
underwent surgery for a pump exchange. Intraoperatively, a firm thrombus was
found within the pump of the HeartMate II, and the color of the urine changed
dramatically from cola-colored to yellow which enabled us to confirm the
diagnosis.
PMID- 25133151
TI - Transthoracic echo: A sensitive tool for detecting cardiac extension of renal
cell carcinoma?
AB - Renal cell carcinoma is a common urological malignancy with the unique ability to
invade the inferior vena cava (IVC) and to extend into the right atrium of the
heart. Of those with Renal cell carcinoma only 4%-25% are found to have IVC
invasion and of those only 2%-10% extend into the right atrium. If treated
surgically, extension of tumor thrombus is not a determinant of survival;
therefore it is imperative to determine the presence and extent of tumor thrombus
in order to determine surgical approach and tumor resection. To date this has
been primarily accomplished by magnetic resonance imaging and computed
tomography. We present a case of 61 years old African American woman in which
transthoracic echocardiography provided a more accurate
determination/characterization of the presence and degree of tumor thrombus and
extension.
PMID- 25133152
TI - Prucalopride-associated acute tubular necrosis.
AB - We report the first case of acute renal failure secondary to prucalopride, a
novel agent for the treatment of chronic constipation. The 75 years old male
patient was initiated on prucalopride after many failed treatments for
constipation following a Whipple's procedure for pancreatic cancer. Within four
months of treatment his creatinine rose from 103 to 285 MUmol/L (eGFR 61 decrease
to 19 mL/min per 1.73 m(2)). He was initially treated with prednisone for
presumed acute interstitial nephritis as white blood casts were seen on urine
microscopy. When no improvement was detected, a core biopsy was performed and
revealed interstitial fibrosis and tubular atrophy. The presence of oxalate and
calcium phosphate crystals were also noted. These findings suggest acute tubular
necrosis which may have been secondary to acute interstitial nephritis or
hemodynamic insult. The use of prednisone may have suppressed signs of
inflammation and therefore the clinical diagnosis was deemed acute interstitial
nephritis causing acute tubular necrosis. There are no previous reports of
prucalopride associated with acute renal failure from the literature, including
previous Phase II and III trials.
PMID- 25133153
TI - Actinic prurigo of the lip: Two case reports.
AB - Actinic prurigo is a photodermatosis that can affect the skin, conjunctiva and
lips. It is caused by an abnormal reaction to sunlight and is more common in high
altitude living people, mainly in indigenous descendants. The diagnosis of
actinic prurigo can be challenging, mainly when lip lesions are the only
manifestation, which is not a common clinical presentation. The aim of this
article is to report two cases of actinic prurigo showing only lip lesions. The
patients were Afro-American and were unaware of possible Indian ancestry.
Clinical exam, photographs, videoroscopy examination and biopsy were performed,
and the diagnosis of actinic prurigo was established. Topical corticosteroid and
lip balm with ultraviolet protection were prescribed with excellent results. The
relevance of this report is to show that although some patients may not
demonstrate the classical clinical presentation of actinic prurigo, the
associated clinical and histological exams are determinants for the correct
diagnosis and successful treatment of this disease.
PMID- 25133154
TI - Appendicitis in double cecal appendix: Case report.
AB - Double cecal appendix is a rare anatomical variation. Approximately 100 cases
have been reported worldwide. It is usually diagnosed incidentally during
emergency appendectomies due to inflammatory processes in the cecal appendix.
CASE PRESENTATION: male, white, 36 years old, obese, presenting with pain in the
lower abdomen for 24 h followed by nausea, vomiting and mild fever. He was
subjected to additional tests, with the leukogram showing leukocytosis and
abdominal ultrasonography depicting cecal appendix with thickened wall, locally
associated with small quantities of liquid and intestinal loop obstruction. He
underwent laparotomy, revealing acute appendicitis. Another intestinal loop
obstruction was identified next to the ileum, leading to recognizing another
cecal appendix after local dissection. Double appendectomy and segmental
iliectomy were performed although not needed. Results of the anatomopathological
examination of the surgical samples showed acute inflammation in the two cecal
appendices. So, performing a routine retroperitoneal release and a complete cecum
evaluation during such surgical procedures is recommended and suggested due to
the possibility of not identifying a second cecal appendix.
PMID- 25133155
TI - Rare large homozygous CFTR gene deletion in an Iranian patient with cystic
fibrosis.
AB - Cystic fibrosis, a common autosomal recessive genetic disorder among Caucasians,
is caused by defects in the transmembrane conductance regulatory (CFTR) gene. The
analysis of CFTR gene mutations is useful to better characterize the disease, and
for preconceptional screening, prenatal and preimplantation genetic diagnosis.
Here we report the results of a genetic analysis in a 16-year-old boy from
southwestern Iran diagnosed as having cystic fibrosis in infancy based on
gastrointestinal and pulmonary manifestations, with positive sweat chloride
tests. He lacked both normal and mutant forms of the fragment corresponding to
the ?F508 allele in initial genetic studies. Multiplex ligation-dependent probe
amplification-based testing revealed a homozygous deletion spanning exons 4 to 10
of the CFTR gene. We predict an in-frame deletion removing 373 amino acids based
on our sequencing results. Determining CFTR gene mutations in patients and their
family members would be helpful to prevent the occurrence of new cases,
especially in populations in which consanguinity is common.
PMID- 25133156
TI - Gastric conduit perforation.
AB - As patients with carcinoma of the esophagus live longer, complications associated
with the use of a gastric conduit are increasing. Ulcers form in the gastric
conduit in 6.6% to 19.4% of patients. There are a few reports of perforation of a
gastric conduit in the English literature. Almost all of these were associated
with serious complications. We report a patient who developed a tension
pneumothorax consequent to spontaneous perforation of an ulcer in the gastric
conduit 7 years after the index surgery in a patient with carcinoma of the
gastroesophageal junction. He responded well to conservative management.
Complications related to a gastric conduit can be because of multiple factors.
Periodic endoscopic surveillance of gastric conduits should be considered as
these are at a higher risk of ulcer formation than a normal stomach. Long term
treatment with proton pump inhibitors may decrease complications. There are no
guidelines for the treatment of a perforated gastric conduit ulcer and the
management should be individualized.
PMID- 25133158
TI - Circuit models and experimental noise measurements of micropipette amplifiers for
extracellular neural recordings from live animals.
AB - Glass micropipettes are widely used to record neural activity from single neurons
or clusters of neurons extracellularly in live animals. However, to date, there
has been no comprehensive study of noise in extracellular recordings with glass
micropipettes. The purpose of this work was to assess various noise sources that
affect extracellular recordings and to create model systems in which novel
micropipette neural amplifier designs can be tested. An equivalent circuit of the
glass micropipette and the noise model of this circuit, which accurately describe
the various noise sources involved in extracellular recordings, have been
developed. Measurement schemes using dead brain tissue as well as extracellular
recordings from neurons in the inferior colliculus, an auditory brain nucleus of
an anesthetized gerbil, were used to characterize noise performance and
amplification efficacy of the proposed micropipette neural amplifier. According
to our model, the major noise sources which influence the signal to noise ratio
are the intrinsic noise of the neural amplifier and the thermal noise from
distributed pipette resistance. These two types of noise were calculated and
measured and were shown to be the dominating sources of background noise for in
vivo experiments.
PMID- 25133159
TI - Some physicochemical remarks on spontaneous emulsification of vitreal tamponades.
AB - The importance of gravitational instability in determining the emulsification of
vitreal tamponades is discussed. Theoretical results and numerical simulations
indicate that the spontaneous formation of water-silicon oil is a rare event and
that the very low concentration of surface active agents cannot justify the
systematic formation of emulsions. The gravitational instabilities seem to play
the main role. Our theoretical results seem in agreement with the experimental
evidences; furthermore they indicate a future research line for the improvement
of endotamponades. Indeed, the use of biodegradable antifoam may avoid the
formation of bubbles and delay the formation of emulsions.
PMID- 25133157
TI - Postactivation potentiation biases maximal isometric strength assessment.
AB - Postactivation potentiation (PAP) is known to enhance force production. Maximal
isometric strength assessment protocols usually consist of two or more maximal
voluntary isometric contractions (MVCs). The objective of this study was to
determine if PAP would influence isometric strength assessment. Healthy male
volunteers (n = 23) performed two five-second MVCs separated by a 180-seconds
interval. Changes in isometric peak torque (IPT), time to achieve it (tPTI),
contractile impulse (CI), root mean square of the electromyographic signal during
PTI (RMS), and rate of torque development (RTD), in different intervals, were
measured. Significant increases in IPT (240.6 +/- 55.7 N.m versus 248.9 +/- 55.1
N.m), RTD (746 +/- 152 N.m.s(-1) versus 727 +/- 158 N.m.s(-1)), and RMS (59.1 +/-
12.2% RMSMAX versus 54.8 +/- 9.4% RMSMAX) were found on the second MVC. tPTI
decreased significantly on the second MVC (2373 +/- 1200 ms versus 2784 +/- 1226
ms). We conclude that a first MVC leads to PAP that elicits significant
enhancements in strength-related variables of a second MVC performed 180 seconds
later. If disconsidered, this phenomenon might bias maximal isometric strength
assessment, overestimating some of these variables.
PMID- 25133161
TI - The bacterial contamination of allogeneic bone and emergence of multidrug
resistant bacteria in tissue bank.
AB - Present study was carried out for the microbiological evaluation of allogeneic
bone processed from femoral heads. A total 60 bacterial isolates comprising five
different species including Streptococcus spp., Staphylococcus spp., Klebsiella
spp., Bacillus spp., and Pseudomonas spp. were characterized based on their
cultural and biochemical characteristics. Average bioburden was ranged from 5.7 *
10(1) to 3.9 * 10(4) cfu/gm. The majority (81.7%) of the microbial contaminants
were detected as Gram positive with the predominant organism being skin commensal
coagulase negative Staphylococci (43.3%). Antimicrobial resistance was evaluated
by the activities of 14 broad and narrow spectrum antibiotic discs. Comparing the
overall pattern, marked resistance was noted against Penicillin and Amoxicillin
100% (60/60). The most effective single antibiotics were Gentamicin, Tobramycin,
and Ofloxacin which were bactericidal against 100% (60/60) isolates. Multidrug
resistance (MDR) was confirmed in 70% (42/60) of the samples. Among them, the
most prevalent antibiotypes were Penicillin, Amoxicillin, Oxacillin, Polymyxin,
and Cefpodoxime (80% of total MDR). The study results revealed higher
contamination rate on bone allografts and recommend the implementation of good
tissue banking practices during tissue procurement, processing, and storage in
order to minimize the chances of contamination.
PMID- 25133160
TI - The role of neurotrophic factors conjugated to iron oxide nanoparticles in
peripheral nerve regeneration: in vitro studies.
AB - Local delivery of neurotrophic factors is a pillar of neural repair strategies in
the peripheral nervous system. The main disadvantage of the free growth factors
is their short half-life of few minutes. In order to prolong their activity, we
have conjugated to iron oxide nanoparticles three neurotrophic factors: nerve
growth factor (betaNGF), glial cell-derived neurotrophic factor (GDNF), and basic
fibroblast growth factor (FGF-2). Comparative stability studies of free versus
conjugated factors revealed that the conjugated neurotrophic factors were
significantly more stable in tissue cultures and in medium at 37 degrees C. The
biological effects of free versus conjugated neurotrophic factors were examined
on organotypic dorsal root ganglion (DRG) cultures performed in NVR-Gel, composed
mainly of hyaluronic acid and laminin. Results revealed that the conjugated
neurotrophic factors enhanced early nerve fiber sprouting compared to the
corresponding free factors. The most meaningful result was that conjugated-GDNF,
accelerated the onset and progression of myelin significantly earlier than the
free GDNF and the other free and conjugated factors. This is probably due to the
beneficial and long-acting effect that the stabilized conjugated-GDNF had on
neurons and Schwann cells. These conclusive results make NVR-Gel enriched with
conjugated-GDNF, a desirable scaffold for the reconstruction of severed
peripheral nerve.
PMID- 25133162
TI - Hypoxia-pretreated human MSCs attenuate acute kidney injury through enhanced
angiogenic and antioxidative capacities.
AB - Hypoxia preconditioning has been confirmed as an effective strategy to enhance
the therapeutic potentials of mesenchymal stem cells (MSCs), such as for
myocardial ischemia. However, whether hypoxia preconditioning would produce
beneficial effects on MSC-based renal repair has not been demonstrated. In the
study, we aimed to determine the feasibility and efficacy of hypoxia
preconditioning to enhance MSC-based therapy of acute kidney injury (AKI). MSCs
were isolated from human adipose tissues. The paracrine effects of MSCs under
normoxia and hypoxia were determined in vitro. Rats of AKI were induced by kidney
I/R surgery and randomly divided into three groups: I/R control receiving PBS
injection; MSC group receiving normal MSC injection; hypoMSC group receiving
hypoxia-preconditioned MSC injection. It was demonstrated in vitro that paracrine
effects of MSCs were significantly enhanced, especially angiogenic factors.
Dihydroethidium (DHE) staining showed that antioxidative activities of MSCs were
significantly enhanced by hypoxia stimulation. Vascularization, apoptosis, and
histological injury were all significantly improved in hypoMSC injected group
compared with that in control and MSC injected groups. Finally, the renal
function was also significantly improved in hypoMSC injected group compared with
that in the other two groups as assessed by the serum creatinine and BUN levels.
PMID- 25133163
TI - Identification of modules related to programmed cell death in CHD based on EHEN.
AB - The formation and death of macrophages and foam cells are one of the major
factors that cause coronary heart disease (CHD). In our study, based on the
Edinburgh Human Metabolic Network (EHMN) metabolic network, we built an enzyme
network which was constructed by enzymes (nodes) and reactions (edges) called the
Edinburgh Human Enzyme Network (EHEN). By integrating the subcellular location
information for the reactions and refining the protein-reaction relationships
based on the location information, we proposed a computational approach to select
modules related to programmed cell death. The identified module was in the EHEN
mitochondria (EHEN-M) and was confirmed to be related to programmed cell death,
CHD pathogenesis, and lipid metabolism in the literature. We expected this method
could analyze CHD better and more comprehensively from the point of programmed
cell death in subnetworks.
PMID- 25133164
TI - Consumption of green coffee reduces blood pressure and body composition by
influencing 11beta-HSD1 enzyme activity in healthy individuals: a pilot crossover
study using green and black coffee.
AB - Dietary polyphenols may have a protective role against the development of CVD.
Thus, we aimed to investigate the effects of green coffee (GC), rich in
chlorogenic acid, and black coffee (BC) on cardiovascular markers. A randomised
pilot crossover study was performed on healthy subjects who consumed both coffees
for 2 weeks. We measured anthropometry, blood pressure, and arterial elasticity
after each intervention and collected urine samples to monitor antioxidant
capacity. Free cortisol and cortisone levels were obtained from urine and
analysed by specific ELISA methods. Systolic blood pressure (P = 0.018) and
arterial elasticity (P = 0.001) were significantly reduced after GC. BMI (P =
0.04 for BC; P = 0.01 for GC) and abdominal fat (P = 0.01 for BC; P = 0.009 for
GC) were also significantly reduced with no changes in energy intake. Urinary
free cortisol was significantly reduced from 125.6 +/- 85.9 nmol/day to 76.0 +/-
54.9 nmol/day following GC and increased to 132.1 +/- 89.1 nmol/day after BC.
Urinary free cortisone increased by 18% following BC and 9% following GC
(nonsignificant). Cortisol/cortisone ratio (indicating 11beta-HSD1 activity) was
reduced after GC (from 3.5 +/- 1.9 to 1.7 +/- 1.04, P = 0.002). This suggests
that GC can play a role in reducing cardiovascular risk factors. Further research
including hypertensive and overweight individuals will now be justified to
clarify whether GC could have a therapeutic role in CVD.
PMID- 25133165
TI - Factors associated with spontaneous clearance of hepatitis C virus in Chinese
population.
AB - Hepatitis C virus (HCV) infections spontaneously clear in approximately 15-45% of
infected individuals. Factors which influence spontaneous HCV clearance remain to
be identified. The purpose of the present study was to identify variables
associated with spontaneous HCV clearance in a referred population of Chinese
patients. The prevalence of host, viral, and environmental factors known to
influence the outcome of HCV infections was compared in 92 HCV spontaneous
clearance subjects and 318 HCV persistent infection subjects. Univariate and
multivariate analyses were performed to identify those factors associated with
spontaneous HCV clearance. In univariate analysis, female gender, a history of
icteric hepatitis, serologic evidence of concurrent HBV infection, and rs12979860
CC genotype were positively associated with spontaneous HCV clearance, while
alcohol consumption was negatively associated with clearance. In multivariate
analysis, female gender, a history of icteric hepatitis, concurrent HBV
infection, and rs12979860 CC genotype remained independent variables associated
with spontaneous HCV clearance. Spontaneous HCV clearance is more likely to occur
in females, subjects with a history of icteric hepatitis, HBV coinfections, and
those with the rs12979860 CC genotype.
PMID- 25133166
TI - Dabigatran in secondary stroke prevention: clinical experience with 106 patients.
AB - INTRODUCTION: Our aim was to analyze our clinical experience with dabigatran
etexilate in secondary stroke prevention. METHODS: We retrospectively included
patients starting dabigatran etexilate for secondary stroke prevention from March
2010 to December 2012. Efficacy and safety variables were registered. RESULTS:
106 patients were included, median follow-up of 12 months (range 1-31). Fifty-six
females (52.8%), mean age 76.4 (range 50-95, SD 9.8), median CHADS2 4 (range 2
6), CHA2DS2-VASc 5 (range 2-9), and HAS-BLED 2 (range 1-5). Indication for
dabigatran etexilate was ischemic stroke in 101 patients and acute cerebral
hemorrhage (CH) due to warfarin in 5 (4.7%). Dabigatran etexilate 110 mg bid was
prescribed in 71 cases (67%) and 150 mg bid was prescribed in the remaining.
Seventeen patients (16%) suffered 20 complications during follow-up. Ischemic
complications (10) were 6 transient ischemic attacks (TIA), 3 ischemic strokes,
and 1 acute coronary syndrome. Hemorrhagic complications (10) were CH (1),
gastrointestinal bleeding (6), mild hematuria (2), and mild metrorrhagia (1),
leading to dabigatran etexilate discontinuation in 3 patients. Patients with
previous CH remained uneventful. Three patients died (pneumonia, congestive heart
failure, and acute cholecystitis) and 9 were lost during follow-up. CONCLUSIONS:
Dabigatran etexilate was safe and effective in secondary stroke prevention in
clinical practice, including a small number of patients with previous history of
CH.
PMID- 25133167
TI - Serum osteopontin level correlates with carotid-femoral pulse wave velocity in
geriatric persons.
AB - Osteopontin (OPN) is involved in the regulation of vascular calcification
processes. The aim of this study was to evaluate the relationship between fasting
serum OPN concentration and carotid-femoral pulse wave velocity (cfPWV) in
geriatric persons. Fasting blood samples were obtained from 93 geriatric persons.
cfPWV were performed by SphygmoCor system. Serum OPN levels were measured using a
commercially available enzyme-linked immunosorbent assay. Geriatric adults who
had diabetes (P = 0.007) or dyslipidemia (P = 0.029) had higher cfPWV levels than
those without diabetes or dyslipidemia. The univariable linear regression
analysis showed that age (P = 0.002), waist circumference (P = 0.048), body mass
index (P = 0.004), systolic blood pressure (P = 0.001), diastolic blood pressure
(P = 0.036), pulse pressure (P = 0.017), creatinine (P = 0.002), and log-OPN
level (P = 0.001) were positively correlated with cfPWV levels, while the high
density lipoprotein cholesterol (HDL-cholesterol) level (P = 0.007) and
glomerular filtration rate (P = 0.001) were negatively correlated with cfPWV
levels among the geriatric adults. Multivariable forward stepwise linear
regression analysis of the significant variables also showed that log-OPN (beta =
0.233, R (2) = 0.123, regression coefficient: 1.868, P = 0.011) was still an
independent predictor of cfPWV levels in geriatric persons.
PMID- 25133168
TI - Pharmaceutical options for triggering of final oocyte maturation in ART.
AB - Since the pioneering days of in vitro fertilization, hCG has been the gold
standard to induce final follicular maturation. We herein reviewed different
pharmaceutical options for triggering of final oocyte maturation in ART. The new
upcoming agent seems to be GnRHa with its potential advantages over hCG trigger.
GnRHa triggering elicits a surge of gonadotropins resembling the natural midcycle
surge of gonadotropins, without the prolonged action of hCG, resulting in the
retrieval of more mature oocytes and a significant reduction in or elimination of
OHSS as compared to hCG triggering. The induction of final follicular maturation
using GnRHa represents a paradigm shift in the ovulation triggering concept in
ART and, thus, a way to develop a safer IVF procedure. Kisspeptins are key
central regulators of the neuroendocrine mechanisms of human reproduction, who
have been shown to effectively elicit an LH surge and to induce final oocyte
maturation in IVF cycles. This new trigger concept may, therefore, offer a
completely new, "natural" pharmacological option for ovulation induction. Whether
kisspeptins will be the future agent to trigger ovulation remains to be further
explored.
PMID- 25133169
TI - Cystic fibrosis and new trends by ophthalmological evaluation: a pilot study.
AB - BACKGROUND: Cystic fibrosis (CF) is characterized by hypoxia that affects several
organic tissues. Retinal ganglion cells may suffer from the hypoxic status, and
this may lead to alterations of retinal nerve fiber. METHODS: Twenty-two eyes in
CF patients were analyzed. A complete ocular evaluation and visual field exams of
the 30 central degrees were performed using the frequency doubling technology
(FDT). Forced expiratory volume in one second (FEV1%), forced vital capacity
(FVC%), oxyhaemoglobin saturation (SpO2%), and hematocrit (Ht%) have been
calculated. FDT analyzed parameters were mean deviation (MD) and pattern standard
deviation (PSD). Pearson's correlation was chosen as statistical analysis.
RESULTS: Data showed statistically significant relationship between MD and Ht% (r
value -0.18; P = 0.04), MD and FEV1% (r value -0.68; P = 0.001), and MD and FVC%
(r value -0.45; P = 0.005). Moreover, there were correlations between PSD and Ht%
(r value 0.29; P = 0.03), PSD and SpO2% (r value -0.31; P = 0.01), PSD and FEV1%
(r value 0.71; P = 0.0005), and PSD and FVC% (r value 0.63; P = 0.003).
CONCLUSIONS: The oxygen supply alterations might determine hypoxia of the
ganglion cells causing a decrease of receptive optic nerve fiber activity. This
method could be also useful to evaluate indirectly pulmonary activity of the CF
disease.
PMID- 25133171
TI - UVA-UVB photoprotective activity of topical formulations containing Morinda
citrifolia extract.
AB - Exposure to solar radiation, particularly its ultraviolet (UV) component, has a
variety of harmful effects on human health. Some of these effects include sunburn
cell formations, basal and squamous cell cancers, melanoma, cataracts, photoaging
of the skin, and immune suppression. The beneficial photoprotective effects of
topical formulations with the extract, Morinda citrifolia, have not been
investigated. This present study aims to investigate the potential benefits of M.
citrifolia topical application on the dorsal skin of mice, exposed to UVA-UVB
light. Using 7 days of treatment, [before (baseline values) and 20 h after UV
exposure], the thickness, skin barrier damage (TEWL), erythema, and histological
alterations were evaluated. The results showed that the formulations containing
the extract protected the skin against UV-induced damage.
PMID- 25133172
TI - Biomarkers in women's cancers, gynecology, and obstetrics.
PMID- 25133170
TI - Intra-QT spectral coherence as a possible noninvasive marker of sustained
ventricular tachycardia.
AB - Sudden cardiac death is the main cause of mortality in patients affected by
chronic heart failure (CHF) and with history of myocardial infarction. No study
yet investigated the intra-QT phase spectral coherence as a possible tool in
stratifying the arrhythmic susceptibility in patients at risk of sudden cardiac
death (SCD). We, therefore, assessed possible difference in spectral coherence
between the ECG segment extending from the q wave to the T wave peak (QTp) and
the one from T wave peak to the T wave end (Te) between patients with and without
Holter ECG-documented sustained ventricular tachycardia (VT). None of the QT
variability indexes as well as most of the coherences and RR power spectral
variables significantly differed between the two groups except for the QTp-Te
spectral coherence. The latter was significantly lower in patients with sustained
VT than in those without (0.508 +/- 0.150 versus 0.607 +/- 0.150, P < 0.05).
Although the responsible mechanism remains conjectural, the QTp-Te spectral
coherence holds promise as a noninvasive marker predicting malignant ventricular
arrhythmias.
PMID- 25133173
TI - Molecular epidemiology of genogroup II noroviruses infection in outpatients with
acute gastroenteritis in Nanjing, China (2010-2013).
AB - OBJECTIVE: Human noroviruses (NoVs) of genogroup II are the most common strains
detected in sporadic cases of acute nonbacterial gastroenteritis in outpatients
in Nanjing. To gain insight into the molecular epidemiology of GII strains, we
analyzed 75 positive NoV cases from 2010 to 2013. METHODS: The sporadic cases
were detected by real-time PCR with specific primers and probes to human NoVs of
genogroup I or II, human sapovirus, human rotavirus, human astrovirus, and human
enteric adenovirus. Human NoVs of genogroup II were further studied by VP1
amplification (RT- PCR), cloning, sequencing, and phylogenetic analysis. RESULTS:
Rotavirus and human NoVs were more frequently detected in all the cases from 2010
to 2013. Human NoVs infection was more frequent since 2011 and more frequent than
rotavirus infection after 2012. Out of the 75 NoV cases of genogroup II, there
were 5 GII.6, 11 GII.3, and 59 GII.4. Of the 59 GII.4, 27 cases were previous
GII.4.2006b strains that circulated between 2010 and 2012; while 32 cases were
the newly emerging GII.4 strains GII.4.2012 from 2011 to 2013. CONCLUSION: Our
data confirm other studies on the rapid emergence and displacement of highly
virulent GII.4 strains.
PMID- 25133175
TI - Adrenergic activation of melatonin secretion in ovine pineal explants in short
term superfusion culture occurs via protein synthesis independent and dependent
phenomena.
AB - The ovine pineal is generally considered as an interesting model for the study on
adrenergic regulation of melatonin secretion due to some functional similarities
with this gland in the human. The present investigations, performed in the
superfusion culture of pineal explants, demonstrated that the norepinephrine
induced elevation of melatonin secretion in ovine pinealocytes comprised of two
subsequent periods: a rapid increase phase and a slow increase phase. The first
one included the quick rise in release of N-acetylserotonin and melatonin,
occurring parallel to elevation of NE concentration in the medium surrounding
explants. This rapid increase phase was not affected by inhibition of
translation. The second, slow increase phase began after NE level had reached the
maximum concentration in the culture medium and lasted about two hours. It was
completely abolished by the treatment with translation inhibitors. The obtained
results showed for the first time that the regulation of N-acetylserotonin
synthesis in pinealocytes of some species like the sheep involves the on/off
mechanism, which is completely independent of protein synthesis and works very
fast. They provided strong evidence pointing to the need of revision of the
current opinion that arylalkylamines N-acetyltransferase activity in pinealocytes
is controlled exclusively by changes in enzyme abundance.
PMID- 25133174
TI - Sphingosine-1-phosphate transporters as targets for cancer therapy.
AB - Sphingosine-1-phosphate (S1P) is a pleiotropic lipid mediator that regulates cell
survival, migration, the recruitment of immune cells, angiogenesis, and
lymphangiogenesis, all of which are involved in cancer progression. S1P is
generated inside cancer cells by sphingosine kinases then exported outside of the
cell into the tumor microenvironment where it binds to any of five G protein
coupled receptors and proceeds to regulate a variety of functions. We have
recently reported on the mechanisms underlying the "inside-out" signaling of S1P,
its export through the plasma membrane, and its interaction with cell surface
receptors. Membrane lipids, including S1P, do not spontaneously exchange through
lipid bilayers since the polar head groups do not readily go through the
hydrophobic interior of the plasma membrane. Instead, specific transporter
proteins exist on the membrane to exchange these lipids. This review summarizes
what is known regarding S1P transport through the cell membrane via ATP-binding
cassette transporters and the spinster 2 transporter and discusses the roles for
these transporters in cancer and in the tumor microenvironment. Based on our
research and the emerging understanding of the role of S1P signaling in cancer
and in the tumor microenvironment, S1P transporters and S1P signaling hold
promise as new therapeutic targets for cancer drug development.
PMID- 25133176
TI - Sensoric protection after median nerve injury: babysitter-procedure prevents
muscular atrophy and improves neuronal recovery.
AB - The babysitter-procedure might offer an alternative when nerve reconstruction is
delayed in order to overcome muscular atrophy due to denervation. In this study
we aimed to show that a sensomotoric babysitter-procedure after median nerve
injury is capable of preserving irreversible muscular atrophy. The median nerve
of 20 female Wistar rats was denervated. 10 animals received a sensory protection
with the N. cutaneous brachii. After six weeks the median nerve was reconstructed
by autologous nerve grafting from the contralateral median nerve in the
babysitter and the control groups. Grasping tests measured functional recovery
over 15 weeks. At the end of the observation period the weight of the flexor
digitorum sublimis muscle was determined. The median nerve was excised for
histological examinations. Muscle weight (P < 0.0001) was significantly superior
in the babysitter group compared to the control group at the end of the study.
The histological evaluation revealed a significantly higher diameter of axons (P
= 0.0194), nerve fiber (P = 0.0409), and nerve surface (P = 0.0184) in the
babysitter group. We conclude that sensory protection of a motor nerve is capable
of preserving muscule weight and we may presume that metabolism of the sensory
nerve was sufficient to keep the target muscle's weight and vitality.
PMID- 25133177
TI - Comparison of the effects of low volume prilocaine and alkalinized prilocaine for
the regional intravenous anesthesia technique in hand and wrist surgery.
AB - AIM: Comparing the effectivity of prilocaine and prilocaine alkalinized with 8.4%
NaHCO3 in terms of sensory and motor block onset and termination durations in
RIVA technique considering patients' satisfaction and tolerance with application
of tourniquet undergoing hand-wrist surgery. MATERIALS AND METHODS: 64 patients
were randomised into two groups. First group (Group P) was administered
prilocaine and second group (Group PN) was administered prilocaine + %8.4 NaHCO3.
Sensory and motor block onset and termination times and onset of tourniquet pain
were recorded. RESULTS: No significant difference was found between the two
groups in terms of onset and termination of sensory block and the onset of motor
block. The duration of the motor block was longer in Group PN than in Group P (P
< 0.05). Tourniquet pain was more intense in Group P (P = 0.036). In Group PN,
the use of additional drugs was recorded at a lower rate and patients'
satisfaction was higher than Group P. CONCLUSION: In the present study, it was
established that alkalinization of prilocaine had no effect on the duration of
sensory block and it prolonged the duration of motor block, increased patients'
satisfaction, and decreased tourniquet pain. It is our suggestion that future
studies should be carried out on the issue by using different volumes.
PMID- 25133178
TI - Physiological and biochemical changes in Brassica juncea plants under Cd-induced
stress.
AB - Plants of Brassica juncea L. var. RLC-1 were exposed for 30 days to different
concentrations (0, 0.2, 0.4, and 0.6 mM) of cadmium (Cd) to analyze the Cd
uptake, H2O2 content, hormonal profiling, level of photosynthetic pigments
(chlorophyll, carotenoid, and flavonoid), gaseous exchange parameters
(photosynthetic rate, vapour pressure deficit, intercellular CO2 concentration,
and intrinsic mesophyll rate), antioxidative enzymes (superoxide dismutase,
polyphenol oxidase, glutathione-S transferase, and glutathione peroxidase),
antioxidant assays (DPPH, ABTS, and total phenolic content), and polyphenols.
Results of the present study revealed the increased H2O2 content and Cd uptake
with increasing metal doses. UPLC analysis of plants showed the presence of
various polyphenols. Gaseous exchange measurements were done by infrared gas
analyzer (IRGA), which was negatively affected by metal treatment. In addition,
LC/MS study showed the variation in the expression of plant hormones. Level of
photosynthetic pigments and activities of antioxidative enzymes were altered
significantly in response to metal treatment. In conclusion, the antioxidative
defence system of plants got activated due to heavy metal stress, which protects
the plants by scavenging free radicals.
PMID- 25133180
TI - Analysis of EEG signals related to artists and nonartists during visual
perception, mental imagery, and rest using approximate entropy.
AB - In this paper, differences between multichannel EEG signals of artists and
nonartists were analyzed during visual perception and mental imagery of some
paintings and at resting condition using approximate entropy (ApEn). It was found
that ApEn is significantly higher for artists during the visual perception and
the mental imagery in the frontal lobe, suggesting that artists process more
information during these conditions. It was also observed that ApEn decreases for
the two groups during the visual perception due to increasing mental load;
however, their variation patterns are different. This difference may be used for
measuring progress in novice artists. In addition, it was found that ApEn is
significantly lower during the visual perception than the mental imagery in some
of the channels, suggesting that visual perception task requires more cerebral
efforts.
PMID- 25133179
TI - Metabolic variations, antioxidant potential, and antiviral activity of different
extracts of Eugenia singampattiana (an endangered medicinal plant used by Kani
tribals, Tamil Nadu, India) leaf.
AB - Eugenia singampattiana is an endangered medicinal plant used by the Kani tribals
of South India. The plant had been studied for its antioxidant, antitumor,
antihyperlipidemic, and antidiabetic activity. But its primary and secondary
metabolites profile and its antiviral properties were unknown, and so this study
sought to identify this aspect in Eugenia singampattiana plant through different
extraction methods along with their activities against porcine reproductive and
respiratory syndrome virus (PRRSV). The GC-MS analysis revealed that 11 primary
metabolites showed significant variations among the extracts. Except for fructose
all other metabolites were high with water extract. Among 12 secondary
metabolites showing variations, the levels of 4-hydroxy benzoic acid, caffeic
acid, rutin, ferulic acid, coumaric acid, epigallocatechin gallate, quercetin,
myricetin, and kaempferol were high with methanol extract. Since the flavonoid
content of methanol extracts was high, the antioxidant potential, such as ABTS,
and phosphomolybdenum activity increased. The plants antiviral activity against
PRRSV was for the first time confirmed and the results revealed that methanol 25
ug and 75 to 100 ug in case of water extracts revealed antiviral activity.
PMID- 25133182
TI - Novel psychoactive substances in young adults with and without psychiatric
comorbidities.
AB - OBJECTIVE: Comorbidities between psychiatric diseases and consumption of
traditional substances of abuse (alcohol, cannabis, opioids, and cocaine) are
common. Nevertheless, there is no data regarding the use of novel psychoactive
substances (NPS) in the psychiatric population. The purpose of this multicentre
survey is to investigate the consumption of a wide variety of psychoactive
substances in a young psychiatric sample and in a paired sample of healthy
subjects. METHODS: A questionnaire has been administered, in different Italian
cities, to 206 psychiatric patients aged 18 to 26 years and to a sample of 2615
healthy subjects matched for sex, gender, and living status. RESULTS: Alcohol
consumption was more frequent in the healthy young population compared to age
matched subjects suffering from mental illness (79.5% versus 70.7%; P < 0.003).
Conversely, cocaine and NPS use was significantly more common in the psychiatric
population (cocaine 8.7% versus 4.6%; P = 0.002) (NPS 9.8% versus 3%; P < 0.001).
CONCLUSIONS: The use of novel psychoactive substances in a young psychiatric
population appears to be a frequent phenomenon, probably still underestimated.
Therefore, careful and constant monitoring and accurate evaluations of possible
clinical effects related to their use are necessary.
PMID- 25133183
TI - Upregulation of relaxin after experimental subarachnoid hemorrhage in rabbits.
AB - BACKGROUND: Although relaxin causes vasodilatation in systemic arteries, little
is known about its role in cerebral arteries. We investigated the expression and
role of relaxin in basilar arteries after subarachnoid hemorrhage (SAH) in
rabbits. METHODS: Microarray analysis with rabbit basilar artery RNA was
performed. Messenger RNA expression of relaxin-1 and relaxin/insulin-like family
peptide receptor 1 (RXFP1) was investigated with quantitative RT-PCR. RXFP1
expression in the basilar artery was investigated with immunohistochemistry.
Relaxin concentrations in cerebrospinal fluid (CSF) and serum were investigated
with an enzyme-linked immunosorbent assay. Using human brain vascular smooth
muscle cells (HBVSMC) preincubated with relaxin, myosin light chain
phosphorylation (MLC) was investigated with immunoblotting after endothelin-1
stimulation. RESULTS: After SAH, RXFP1 mRNA and protein were significantly
downregulated on day 3, whereas relaxin-1 mRNA was significantly upregulated on
day 7. The relaxin concentration in CSF was significantly elevated on days 5 and
7. Pretreatment with relaxin reduced sustained MLC phosphorylation induced by
endothelin-1 in HBVSMC. CONCLUSION: Upregulation of relaxin and downregulation of
RXFP1 after SAH may participate in development of cerebral vasospasm.
Downregulation of RXFP1 may induce a functional decrease in relaxin activity
during vasospasm. Understanding the role of relaxin may provide further insight
into the mechanisms of cerebral vasospasm.
PMID- 25133185
TI - Amino-functionalization of carbon nanotubes by using a factorial design: human
cardiac troponin T immunosensing application.
AB - A simple amino-functionalization method for carbon nanotubes and its application
in an electrochemical immunosensor for detection of the human cardiac troponin T
are described. Amino-functionalized carbon nanotubes allow oriented antibodies
immobilization via their Fc regions, improving the performance of an
immunosensor. Herein multiwalled carbon nanotubes were amino-functionalized by
using the ethylenediamine reagent and assays were designed by fractional
factorial study associated with Doehlert matrix. Structural modifications in the
carbon nanotubes were confirmed by Fourier transform infrared spectroscopy. After
amino-functionalization the carbon nanotubes were attached to screen-printed
carbon electrode and a sandwich-type immunoassay was performed for measuring the
cardiac troponin T. The electrochemical measurements were obtained through
hydrogen peroxide reaction with peroxidase conjugated to the secondary antibody.
Under optimal conditions, troponin T immunosensor was evaluated in serum samples,
which showed a broad linear range (0.02 to 0.32 ng mL(-1)) and a low limit of
detection, 0.016 ng mL(-1). This amino platform can be properly used as clinical
tool for cardiac troponin T detection in the acute myocardial infarction
diagnosis.
PMID- 25133186
TI - Anti-inflammatory effect and mechanism of the green fruit extract of Solanum
integrifolium Poir.
AB - The green fruit of Solanum integrifolium Poir. has been used traditionally as an
anti-inflammatory and analgesic remedy in Taiwanese aboriginal medicine. The goal
of this study is to evaluate the anti-inflammatory activity and mechanism of the
green fruit extract of S. integrifolium. A bioactivity-guided fractionation
procedure was developed to identify the active partition fraction. The methanol
fraction (ME), with the highest phenolic content, exhibited the strongest
inhibitory effect against LPS-mediated nitric oxide (NO) release and cytotoxicity
in RAW264.7 macrophages. ME also significantly downregulated the expression of
LPS-induced proinflammatory genes, such as iNOS, COX-2, IL-1beta, IL-6, CCL2/MCP
1, and CCL3/MIP1alpha. Moreover, ME significantly upregulated HO-1 expression and
stimulated the activation of extracellular-signal-regulated kinase 1/2 (ERK1/2).
Pretreatment of cells with the HO-1 inhibitor zinc protoporphyrin and MEK/ERK
inhibitor U0126 attenuated ME's inhibitory activity against LPS-induced NO
production. Taken together, this is the first study to demonstrate the anti
inflammatory activity of green fruit extract of S. integrifolium and its activity
may be mediated by the upregulation of HO-1 expression and activation of ERK1/2
pathway.
PMID- 25133184
TI - Behavioral and psychological symptoms in Alzheimer's disease.
AB - Neuropsychiatric symptoms (NPS) such as depression, apathy, aggression, and
psychosis are now recognized as core features of Alzheimer's disease (AD), and
there is a general consensus that greater symptom severity is predictive of
faster cognitive decline, loss of independence, and even shorter survival.
Whether these symptoms result from the same pathogenic processes responsible for
cognitive decline or have unique etiologies independent of AD-associated
neurodegeneration is unclear. Many structural and metabolic features of the AD
brain are associated with individual neuropsychiatric symptoms or symptom
clusters. In addition, many genes have been identified and confirmed that are
associated with symptom risk in a few cases. However, there are no single genes
strongly predictive of individual neuropsychiatric syndromes, while functional
and structural brain changes unique to specific symptoms may reflect variability
in progression of the same pathological processes. Unfortunately, treatment
success for these psychiatric symptoms may be lower when comorbid with AD,
underscoring the importance of future research on their pathobiology and
treatment. This review summarizes some of the most salient aspects of NPS
pathogenesis.
PMID- 25133188
TI - Gravity affects the closure of the traps in Dionaea muscipula.
AB - Venus flytrap (Dionaea muscipula Ellis) is a carnivorous plant known for its
ability to capture insects thanks to the fast snapping of its traps. This fast
movement has been long studied and it is triggered by the mechanical stimulation
of hairs, located in the middle of the leaves. Here we present detailed
experiments on the effect of microgravity on trap closure recorded for the first
time during a parabolic flight campaign. Our results suggest that gravity has an
impact on trap responsiveness and on the kinetics of trap closure. The possible
role of the alterations of membrane permeability induced by microgravity on trap
movement is discussed. Finally we show how the Venus flytrap could be an easy and
effective model plant to perform studies on ion channels and aquaporin
activities, as well as on electrical activity in vivo on board of parabolic
flights and large diameter centrifuges.
PMID- 25133187
TI - Molecular mechanisms for biliary phospholipid and drug efflux mediated by ABCB4
and bile salts.
AB - On the canalicular membranes of hepatocytes, several ABC transporters are
responsible for the secretion of bile lipids. Among them, ABCB4, also called
MDR3, is essential for the secretion of phospholipids from hepatocytes into bile.
The biliary phospholipids are associated with bile salts and cholesterol in mixed
micelles, thereby reducing the detergent activity and cytotoxicity of bile salts
and preventing cholesterol crystallization. Mutations in the ABCB4 gene result in
progressive familial intrahepatic cholestasis type 3, intrahepatic cholestasis of
pregnancy, low-phospholipid-associated cholelithiasis, primary biliary cirrhosis,
and cholangiocarcinoma. In vivo and cell culture studies have demonstrated that
the secretion of biliary phospholipids depends on both ABCB4 expression and bile
salts. In the presence of bile salts, ABCB4 located in nonraft membranes mediates
the efflux of phospholipids, preferentially phosphatidylcholine. Despite high
homology with ABCB1, ABCB4 expression cannot confer multidrug resistance. This
review summarizes our current understanding of ABCB4 functions and physiological
relevance, and discusses the molecular mechanism for the ABCB4-mediated efflux of
phospholipids.
PMID- 25133190
TI - Compensatory mechanisms of pancreatic beta cells: insights into the therapeutic
perspectives for diabetes.
PMID- 25133189
TI - Harnessing the helminth secretome for therapeutic immunomodulators.
AB - Helminths are the largest and most complex pathogens to invade and live within
the human body. Since they are not able to outpace the immune system by rapid
antigen variation or faster cell division or retreat into protective niches not
accessible to immune effector mechanisms, their long-term survival depends on
influencing and regulating the immune responses away from the mode of action most
damaging to them. Immunologists have focused on the excretory and secretory
products that are released by the helminths, since they can change the host
environment by modulating the immune system. Here we give a brief overview of the
helminth-associated immune response and the currently available helminth
secretome data. We introduce some major secretome-derived immunomodulatory
molecules and describe their potential mode of action. Finally, the applicability
of helminth-derived therapeutic proteins in the treatment of allergic and
autoimmune inflammatory disease is discussed.
PMID- 25133191
TI - Chicken embryos as a potential new model for early onset type I diabetes.
AB - Diabetic retinopathy (DR) is the leading cause of blindness among the American
working population. The purpose of this study is to establish a new diabetic
animal model using a cone-dominant avian species to address the distorted color
vision and altered cone pathway responses in prediabetic and early diabetic
patients. Chicken embryos were injected with either streptozotocin (STZ), high
concentration of glucose (high-glucose), or vehicle at embryonic day 11.
Cataracts occurred in varying degrees in both STZ- and high glucose-induced
diabetic chick embryos at E18. Streptozotocin-diabetic chicken embryos had
decreased levels of blood insulin, glucose transporter 4 (Glut4), and
phosphorylated protein kinase B (pAKT). In STZ-injected E20 embryos, the ERG
amplitudes of both a- and b-waves were significantly decreased, the implicit time
of the a-wave was delayed, while that of the b-wave was significantly increased.
Photoreceptors cultured from STZ-injected E18 embryos had a significant decrease
in L-type voltage-gated calcium channel (L-VGCC) currents, which was reflected in
the decreased level of L-VGCCalpha1D subunit in the STZ-diabetic retinas. Through
these independent lines of evidence, STZ-injection was able to induce
pathological conditions in the chicken embryonic retina, and it is promising to
use chickens as a potential new animal model for type I diabetes.
PMID- 25133192
TI - Association of serum vaspin and adiponectin levels with renal function in
patients with or without type 2 diabetes mellitus.
AB - Vaspin and adiponectin are two adipocytokines with antidiabetic effects. Some
studies reported that levels of adiponectin and vaspin were correlated with
decreased glomerular filtration rate (FGR) and increased albuminuria. We
therefore evaluated the vaspin and adiponectin levels in renal insufficiency (RI)
patients with or without T2DM. Serum vaspin, adiponectin levels were measured in
416 subjects with or without T2DM. Analysis was made between groups divided by
these subjects presence or absence of RI. We found that serum adiponectin level
was significantly higher in nondiabetic patients with RI than in nondiabetic
subjects without RI; however, there were no statistical differences between the
diabetic patients with RI and without RI. In all the subjects, the serum
adiponectin level was also higher in 50 individuals with RI than that in 366
subjects without RI. The serum vaspin levels showed no significant differences
between the diabetic patients or nondiabetics subjects with RI and without RI.
Contrary to adiponectin, the serum vaspin level was lower in 169 patients with
T2DM than in 247 individuals without T2DM. Our data suggested that both of T2DM
and renal insufficiency were correlated with the serum level of adiponectin.
However, the serum vaspin levels showed no significant difference between the
individuals with renal insufficiency and without renal insufficiency.
PMID- 25133193
TI - Tribbles 3 regulates the fibrosis cytokine TGF- beta 1 through ERK1/2-MAPK
signaling pathway in diabetic nephropathy.
AB - To reveal the expression and possible role of tribbles homolog 3 (TRB3) in the
incidence of type 2 diabetic nephropathy, we used immunohistochemistry, real-time
quantitative PCR, western blot analysis, and enzyme-linked immunosorbent assay
(ELISA) to study the expression of TRB3, extracellular signal-regulated kinase
1/2 mitogen-activated protein kinase (ERK1/2 MAPK), transforming growth factor
beta1 (TGF-beta1), and collagen type IV in kidneys of db/db diabetic mice and in
murine renal mesangial cells stimulated with high glucose. The expression of
TRB3, TGF-beta1, and collagen type IV was increased in kidneys of db/db diabetic
mice. TGF-beta1 and collagen type IV regulated by high glucose through ERK1/2
MAPK were downregulated by silencing TRB3 in renal mesangial cells. TRB3 may be
involved in diabetic nephropathy by regulating the fibrosis cytokine TGF-beta1
and collagen type IV through the ERK1/2 MAPK signaling pathway.
PMID- 25133194
TI - Activation effects of polysaccharides of Flammulina velutipes mycorrhizae on the
T lymphocyte immune function.
AB - Flammulina velutipes mycorrhizae have increasingly been produced with increasing
of F. velutipes production. A mouse model was thus used to examine potential
effect of F. velutipes mycorrhizae on the immune function. Fifty female Wistar
mice (5-weeks-old) weighed 15-20 g were randomly allocated into five groups.
Polysaccharide of F. velutipes mycorrhizae were treated with mice and mice spleen
lymphocytes. The levels of CD3(+), CD4(+), and CD8(+) T lymphocyte, interleukin-2
(IL-2), and tumor necrosis factor-a (TNF-alpha) were determined. The results
showed that the proportions of CD3(+), and CD4(+) T lymphocyte, the ratio of
CD4(+)/CD8(+), and the levels of IL-2 and TNF-a were significantly increased in
polysaccharide of F. velutipes mycorrhizae, while the proportion of CD8(+) T
lymphocyte was decreased in polysaccharide of F. velutipes mycorrhizae-dose
dependent manner. Our findings indicated that a long term exposure of
polysaccharide of F. velutipes mycorrhizae could activate the T lymphocyte immune
function. Polysaccharide of F. velutipes mycorrhizae was expected to develop into
the immune health products.
PMID- 25133195
TI - Cardiovascular risk factors in the antiphospholipid syndrome.
AB - A major cause of morbidity and mortality in the context of the antiphospholipid
syndrome (APS) is the occurrence of thrombotic events. Besides the pathogenic
roles of antiphospholipid antibodies (aPL), other risk factors and medical
conditions, which are conditions for traditional risk of an individual without
the APS, can coexist in this patient, raising their risk of developing
thrombosis. Therefore, the clinical and laboratory investigation of comorbidities
known to increase cardiovascular risk in patients with antiphospholipid antibody
syndrome is crucial for the adoption of a more complete and effective treatment.
Experimental models and clinical studies show evidence of association between APS
and premature formation of atherosclerotic plaques. Atherosclerosis has major
traditional risk factors: hypertension, diabetes mellitus, obesity, dyslipidemia,
smoking, and sedentary lifestyle that may be implicated in vascular involvement
in patients with APS. The influence of nontraditional risk factors as
hyperhomocysteinemia, increased lipoprotein a, and anti-oxLDL in the development
of thromboembolic events in APS patients has been studied in scientific
literature. Metabolic syndrome with all its components also has been recently
studied in antiphospholipid syndrome and is associated with arterial events.
PMID- 25133196
TI - T CD3+CD8+ lymphocytes are more susceptible for apoptosis in the first trimester
of normal human pregnancy.
AB - AIMS: Normal human pregnancy is a complex process of many immunoregulatory
mechanisms which protect fetus from the activation of the maternal immune system.
The aim of the study was to investigate the apoptosis of lymphocytes in
peripheral blood of normal pregnant patients and healthy nonpregnant women.
METHODS: Sixty pregnant women and 17 nonpregnant women were included in the
study. Lymphocytes were isolated and labeled with anti-CD3, anti-CD4, and anti
CD8 monoclonal antibodies. Apoptosis was detected by CMXRos staining and analyzed
using the flow cytometric method. RESULTS: We found significantly higher
apoptosis of total lymphocytes in peripheral blood of pregnant patients when
compared to healthy nonpregnant women. The percentage of apoptotic T CD3(+)CD8(+)
cells in the first trimester was significantly higher when compared to the third
trimester of normal pregnancy. The ratio of T CD3(+)CD4(+) : T CD3(+)CD8(+)
apoptotic lymphocytes was significantly lower in the first trimester when
compared to other trimesters of pregnancy and to both of the phases of the
menstrual cycle. CONCLUSIONS: The higher apoptosis of T CD3(+)CD8(+) lymphocytes
and the lower ratio of T CD3(+)CD4(+) : T CD3(+)CD8(+) apoptotic cells in the
first trimester of normal pregnancy may suggest a higher susceptibility of T
CD3(+)CD8(+) cells for apoptosis as a protective mechanism at the early stage of
pregnancy.
PMID- 25133197
TI - Clinical, laboratory, and therapeutic analyses of 21 patients with neonatal
thrombosis and antiphospholipid antibodies: a literature review.
AB - OBJECTIVES: A review of the literature reports neonatal thrombosis and
antiphospholipid antibodies cases through a retrospective study that focuses on
the pathogenesis and main clinical and laboratory manifestations of this disease.
METHODS: The case reports were selected from PubMed. The keywords used to search
were neonatal, antiphospholipid syndrome, thrombosis, and antiphospholipid
antibodies. References that were published from 1987 to 2013 were reviewed.
RESULTS: Twenty-one cases of neonatal thrombosis and antiphospholipid antibodies
were identified. Ten children were born preterm (before 37 weeks). Arterial
involvement (17/21) was predominant, of which stroke (12/17) was the most
prevalent clinical manifestation. Anti-cardiolipin antibodies were predominant
(13/21) in the antiphospholipid antibody profiles. Treatments were based on the
use of symptomatics such as antiepileptics (8/21), and 6/21 patients received
heparin. There were 4 deaths (4/21); otherwise, the children recovered well,
especially the neonates who suffered from strokes (9/12). CONCLUSION: Neonatal
thrombosis and antiphospholipid antibodies are rare. The development of
thrombotic manifestations in neonates seems not to be associated exclusively with
the aPL, but their etiology may be linked to pre- and perinatal events. We noted
good therapeutic responses, especially in stroke patients, who presented with
favorable outcomes in 82% of the cases.
PMID- 25133198
TI - Uncomplicated diverticular disease: innate and adaptive immunity in human gut
mucosa before and after rifaximin.
AB - BACKGROUND/AIM: Uncomplicated diverticular disease (UDD) is a frequent condition
in adults. The pathogenesis of symptoms remains unknown. Bacteria are able to
interact with Toll-like receptors (TLRs) and to induce inflammation through both
innate immunity and T-cell recruitment. We investigated the pattern of TLRs 2 and
4 and the intestinal homing in patients with UDD before and after a course of
Rifaximin. METHODS: Forty consecutive patients with UDD and 20 healthy
asymptomatic subjects were enrolled. Among UDD patients, 20 were assigned to a 2
month course of treatment with Rifaximin 1.2 g/day for 15 days/month and 20
received placebo. Blood sample and colonic biopsies were obtained from patients
and controls. The samples were collected and analyzed at baseline and at the end
of treatment. Flow cytometry was performed using monoclonal antibodies (CD3, CD4,
CD8, CD103, TCR-gamma/delta, CD14, TLR2, and TLR4). RESULTS: In UDD, TLR2 and
TLR4 expression on immune cell subpopulations from blood and mucosa of the
affected colon are altered as compared with controls. Rifaximin treatment induced
significant modifications of altered conditions. CONCLUSIONS: Our data show the
role of TLRs in the development of inflammation in UDD. TLRs distribution is
altered in UDD and these alterations are reversed after antibiotic treatment.
This trial is registered with ClinicalTrials.gov: NCT02068482.
PMID- 25133199
TI - SOCS1 and regulation of regulatory T cells plasticity.
AB - Several reports have suggested that natural regulatory T cells (Tregs) lose
Forkhead box P3 (Foxp3) expression and suppression activity under certain
inflammatory conditions. Treg plasticity has been studied because it may be
associated with the pathogenesis of autoimmunity. Some studies showed that a
minor uncommitted Foxp3(+) T cell population, which lacks hypomethylation at Treg
specific demethylation regions (TSDRs), may convert to effector/helper T cells.
Suppressor of cytokine signaling 1 (SOCS1), a negative regulator of cytokine
signaling, has been reported to play an important role in Treg cell integrity and
function by protecting the cells from excessive inflammatory cytokines. In this
review, we discuss Treg plasticity and maintenance of suppression functions in
both physiological and pathological settings. In addition, we discuss molecular
mechanisms of maintaining Treg plasticity by SOCS1 and other molecules. Such
information will be useful for therapy of autoimmune diseases and reinforcement
of antitumor immunity.
PMID- 25133200
TI - Optical imaging in an Alzheimer's mouse model reveals amyloid-beta-dependent
vascular impairment.
AB - Alzheimer's disease (AD) and cerebrovascular disease are often comorbid
conditions, but the relationship between amyloid-beta and in vivo vascular
pathophysiology is poorly understood. We utilized a multimodal, multiscale
optical imaging approach, including spatial frequency domain imaging, Doppler
optical coherence tomography, and confocal microscopy, to quantify AD-dependent
changes in a triple transgenic mouse model (3xTg-AD) and age-matched controls.
From three months of age (naive) to 20 months (severe AD), the brain tissue
concentration of total and oxy-hemoglobin (Total Hb, ctO2Hb) decreased 50 and
70%, respectively, in 3xTg-AD mice. Compared to age-matched controls, significant
differences in brain hemoglobin concentrations occurred as early as eight months
(Total Hb: 126 +/- 5 MUM versus 108 +/- 4 MUM; ctO2Hb: 86 +/- 5 MUM versus 70 +/-
3 MUM; for control and AD, respectively). These changes were linked to a 29%
vascular volume fraction decrease and 35% vessel density reduction in the 20
month-old 3xTg-AD versus age-matched controls. Vascular reduction coincided with
increased brain concentration of amyloid-beta protein, vascular endothelial
growth factor (VEGF), and endothelial nitric oxide synthase (eNOS) at eight and
20 months compared to the three-month baseline. Our results suggest that amyloid
beta blocks the normally reparative effects of upregulated VEGF and eNOS, and may
accelerate in vivo vascular pathophysiology in AD.
PMID- 25133202
TI - Malware analysis using visualized image matrices.
AB - This paper proposes a novel malware visual analysis method that contains not only
a visualization method to convert binary files into images, but also a similarity
calculation method between these images. The proposed method generates RGB
colored pixels on image matrices using the opcode sequences extracted from
malware samples and calculates the similarities for the image matrices.
Particularly, our proposed methods are available for packed malware samples by
applying them to the execution traces extracted through dynamic analysis. When
the images are generated, we can reduce the overheads by extracting the opcode
sequences only from the blocks that include the instructions related to staple
behaviors such as functions and application programming interface (API) calls. In
addition, we propose a technique that generates a representative image for each
malware family in order to reduce the number of comparisons for the
classification of unknown samples and the colored pixel information in the image
matrices is used to calculate the similarities between the images. Our
experimental results show that the image matrices of malware can effectively be
used to classify malware families both statically and dynamically with accuracy
of 0.9896 and 0.9732, respectively.
PMID- 25133203
TI - Bird diversity and distribution in relation to urban landscape types in northern
Rwanda.
AB - Using the point count method, linear mixed models, Shannon's diversity index, and
Bray-Curtis cluster analysis, we conducted a study of the effect of urban fabric
layout on bird diversity and distribution in northern Rwanda. The results showed
a significant effect of city landscapes on bird richness and relative abundance;
residential neighborhoods, institutional grounds, and informal settlements had
the highest species diversity in comparison to other microlandscape types.
Riversides were characterized by specialized bird species, commonly known to be
restricted to wetland environments. Built-up areas and open field landscapes had
comparable results. One Albertine Rift endemic bird species, the Ruwenzori Double
collared Sunbird (Cinnyris stuhlmanni), was recorded. Three migratory birds were
found in Musanze city for the first time: the Common Sandpiper (Actitis
hypoleucos), the Spotted Flycatcher (Muscicapa striata), and the Willow Warbler
(Phylloscopus trochilus). Two bird species have not been previously reported in
Rwanda: the Garden Warbler (Sylvia borin) and the Lesser Spotted Eagle (Aquila
pomarina). The implications of this study are particularly relevant to urban
decision makers who should consider the existence of a great diversity of avian
fauna when developing and implementing master plans, especially when villages and
cities are in proximity of protected areas or natural reserves.
PMID- 25133201
TI - TRANSCRIPTION FACTOR GLI-SIMILAR 3 (GLIS3): IMPLICATIONS FOR THE DEVELOPMENT OF
CONGENITAL HYPOTHYROIDISM.
AB - Congenital hypothyroidism (CH) is the most frequent endocrine disorder in
neonates. While several genetic mutations have been identified that result in
developmental defects of the thyroid gland or thyroid hormone synthesis, genetic
factors have yet to be identified in many CH patients along with the mechanisms
underlying their pathophysiology. Mutations in the gene encoding the Kruppel-like
transcription factor, GLI-similar 3 (GLIS3) have been associated with the
development of a syndrome characterized by congenital hypothyroidism and neonatal
diabetes and similar phenotypes were observed in mouse knockout models of Glis3.
Patients with GLIS3-mediated CH exhibit diminished serum levels of thyroxine (T4)
and triiodothyronine (T3) and elevated thyroid stimulating hormone (TSH) and
thyroglobulin (TG). However, the inconsistent presentation of clinical features
associated with this CH has made it difficult to ascertain a causative mechanism.
Future elucidation of the biological functions of GLIS3 in the thyroid will be
crucial to the discovery of new therapeutic opportunities for the treatment of
CH.
PMID- 25133204
TI - A community-based walk-in screening of depression in Taiwan.
AB - Depression is a crucial public health problem because of its relatively high
association with suicidal attempts, prolonged social isolation, poor physical
health, and dementia. However, the available data and study on the prevalence of
depression in Taiwan were mostly completed within the previous 1 to 2 decades,
and these studies were limited to certain areas or populations. Little is known
regarding the current status of depression in Taiwan. We used a brief tool, the
Center for Epidemiological Studies Depression Scale (CES-D), to screen depression
in 4 areas among the general and aged population. The results showed a higher CES
D score in the southern area among general (mean +/- SD: 7.8 +/- 8.4) or aged
participants (mean +/- SD: 7.2 +/- 8.0) compared with other areas. The ratio of
suspected depression patients was 16.4% of all recruited participants and 13.3%
of aged participants. These results may provide information for this public
health issue.
PMID- 25133206
TI - A sequential optimization sampling method for metamodels with radial basis
functions.
AB - Metamodels have been widely used in engineering design to facilitate analysis and
optimization of complex systems that involve computationally expensive simulation
programs. The accuracy of metamodels is strongly affected by the sampling
methods. In this paper, a new sequential optimization sampling method is
proposed. Based on the new sampling method, metamodels can be constructed
repeatedly through the addition of sampling points, namely, extrema points of
metamodels and minimum points of density function. Afterwards, the more accurate
metamodels would be constructed by the procedure above. The validity and
effectiveness of proposed sampling method are examined by studying typical
numerical examples.
PMID- 25133207
TI - Vague congruences and quotient lattice implication algebras.
AB - The aim of this paper is to further develop the congruence theory on lattice
implication algebras. Firstly, we introduce the notions of vague similarity
relations based on vague relations and vague congruence relations. Secondly, the
equivalent characterizations of vague congruence relations are investigated.
Thirdly, the relation between the set of vague filters and the set of vague
congruences is studied. Finally, we construct a new lattice implication algebra
induced by a vague congruence, and the homomorphism theorem is given.
PMID- 25133208
TI - Utilizing optical coherence tomography in the nondestructive and noncontact
measurement of egg shell thickness.
AB - The goal of this study was to measure the thickness of egg shells without any
contact and by utilizing a nondestructive method that sends infrared light beam
on the egg. We obtain measurement resolutions on the order of 7 MUm up to a
penetration depth of 1.7 mm from the actual surface of the egg shell. The
measurement results we obtained show that optical coherence tomography can be
used to accurately determine the egg shell thickness. Scanning the light beam
over the surface allows for measuring the egg profile and monitoring the
variations of shell thickness. Since this information gives a quantitative value
for the uniformity of the egg shell structure, we anticipate that optical
coherence tomography may be used in the quantitative evaluation of egg quality in
in-line automated inspection systems.
PMID- 25133205
TI - Plasminogen activator inhibitor-1 regulates LPS induced inflammation in rat
macrophages through autophagy activation.
AB - BACKGROUND: The mechanisms by which plasminogen activator inhibitor-1 (PAI-1)
regulates inflammation, especially in acute respiratory distress syndrome (ARDS),
are largely unknown. OBJECTIVE: To assess the relationship between PAI-1 and
autophagy in inflammatory reactions induced by LPS in rat NR8383 cells. METHODS:
ELISA was used to assess the amounts of TNF-alpha, IL-1beta, and PAI-1 in cell
culture supernatants; TLR4, MyD88, PAI-1, LC3, Beclin1, and mTOR protein and mRNA
levels were determined by western blot and quantitative RT-PCR, respectively;
western blot was used to determine NF-kappaB protein levels. To further evaluate
the role of PAI-1, the PAI-1 gene was downregulated and overexpressed using the
siRNA transfection technology and the pCDH-PAI-1, respectively. Finally, the GFP
Positive Expression Rate Method was used to determine the rate of GFP-LC3
positive NR8383 cells. RESULTS: In LPS-induced NR8383 cells, TNF-alpha, IL-1beta,
and PAI-1 expression levels increased remarkably. Upon PAI-1 knockdown, TNF
alpha, IL-1beta, PAI-1, TLR4, MyD88, NF-kappaB, LC3, and Beclin1 levels were
decreased, while mTOR increased. Conversely, overexpression of PAI-1 resulted in
increased amounts of TNF-alpha, IL-1beta, PAI-1, TLR4, MyD88, NF-kappaB, LC3, and
Beclin1. However, no significant change was observed in mTOR expression.
CONCLUSIONS: In NR8383 cells, PAI-1 contributes in the regulation of LPS-induced
inflammation, likely by promoting autophagy.
PMID- 25133209
TI - Modeling the propagation of mobile phone virus under complex network.
AB - Mobile phone virus is a rogue program written to propagate from one phone to
another, which can take control of a mobile device by exploiting its
vulnerabilities. In this paper the propagation model of mobile phone virus is
tackled to understand how particular factors can affect its propagation and
design effective containment strategies to suppress mobile phone virus. Two
different propagation models of mobile phone viruses under the complex network
are proposed in this paper. One is intended to describe the propagation of user
tricking virus, and the other is to describe the propagation of the vulnerability
exploiting virus. Based on the traditional epidemic models, the characteristics
of mobile phone viruses and the network topology structure are incorporated into
our models. A detailed analysis is conducted to analyze the propagation models.
Through analysis, the stable infection-free equilibrium point and the stability
condition are derived. Finally, considering the network topology, the numerical
and simulation experiments are carried out. Results indicate that both models are
correct and suitable for describing the spread of two different mobile phone
viruses, respectively.
PMID- 25133210
TI - Features extraction of flotation froth images and BP neural network soft-sensor
model of concentrate grade optimized by shuffled cuckoo searching algorithm.
AB - For meeting the forecasting target of key technology indicators in the flotation
process, a BP neural network soft-sensor model based on features extraction of
flotation froth images and optimized by shuffled cuckoo search algorithm is
proposed. Based on the digital image processing technique, the color features in
HSI color space, the visual features based on the gray level cooccurrence matrix,
and the shape characteristics based on the geometric theory of flotation froth
images are extracted, respectively, as the input variables of the proposed soft
sensor model. Then the isometric mapping method is used to reduce the input
dimension, the network size, and learning time of BP neural network. Finally, a
shuffled cuckoo search algorithm is adopted to optimize the BP neural network
soft-sensor model. Simulation results show that the model has better
generalization results and prediction accuracy.
PMID- 25133212
TI - A mobile anchor assisted localization algorithm based on regular hexagon in
wireless sensor networks.
AB - Localization is one of the key technologies in wireless sensor networks (WSNs),
since it provides fundamental support for many location-aware protocols and
applications. Constraints of cost and power consumption make it infeasible to
equip each sensor node in the network with a global position system (GPS) unit,
especially for large-scale WSNs. A promising method to localize unknown nodes is
to use several mobile anchors which are equipped with GPS units moving among
unknown nodes and periodically broadcasting their current locations to help
nearby unknown nodes with localization. This paper proposes a mobile anchor
assisted localization algorithm based on regular hexagon (MAALRH) in two
dimensional WSNs, which can cover the whole monitoring area with a boundary
compensation method. Unknown nodes calculate their positions by using
trilateration. We compare the MAALRH with HILBERT, CIRCLES, and S-CURVES
algorithms in terms of localization ratio, localization accuracy, and path
length. Simulations show that the MAALRH can achieve high localization ratio and
localization accuracy when the communication range is not smaller than the
trajectory resolution.
PMID- 25133211
TI - Detoxification of corncob acid hydrolysate with SAA pretreatment and xylitol
production by immobilized Candida tropicalis.
AB - Xylitol fermentation production from corncob acid hydrolysate has become an
attractive and promising process. However, corncob acid hydrolysate cannot be
directly used as fermentation substrate owing to various inhibitors. In this
work, soaking in aqueous ammonia (SAA) pretreatment was employed to reduce the
inhibitors in acid hydrolysate. After detoxification, the corncob acid
hydrolysate was fermented by immobilized Candida tropicalis cell to produce
xylitol. Results revealed that SAA pretreatment showed high delignification and
efficient removal of acetyl group compounds without effect on cellulose and xylan
content. Acetic acid was completely removed, and the content of phenolic
compounds was reduced by 80%. Furthermore, kinetic behaviors of xylitol
production by immobilized C. tropicalis cell were elucidated from corncob acid
hydrolysate detoxified with SAA pretreatment and two-step adsorption method,
respectively. The immobilized C. tropicalis cell showed higher productivity
efficiency using the corncob acid hydrolysate as fermentation substrate after
detoxification with SAA pretreatment than by two-step adsorption method in the
five successive batch fermentation rounds. After the fifth round fermentation,
about 60 g xylitol/L fermentation substrate was obtained for SAA pretreatment
detoxification, while about 30 g xylitol/L fermentation substrate was obtained
for two-step adsorption detoxification.
PMID- 25133213
TI - Hydraulic transients in the long diversion-type hydropower station with a complex
differential surge tank.
AB - Based on the theory of hydraulic transients and the method of characteristics
(MOC), a mathematic model of the differential surge tank with pressure-reduction
orifices (PROs) and overflow weirs for transient calculation is proposed. The
numerical model of hydraulic transients is established using the data of a
practical hydropower station; and the probable transients are simulated. The
results show that successive load rejection is critical for calculating the
maximum pressure in spiral case and the maximum rotating speed of runner when the
bifurcated pipe is converging under the surge tank in a diversion-type hydropower
station; the pressure difference between two sides of breast wall is large during
transient conditions, and it would be more serious when simultaneous load
rejections happen after load acceptance; the reasonable arrangement of PROs on
breast wall can effectively decrease the pressure difference.
PMID- 25133214
TI - A novel user classification method for femtocell network by using affinity
propagation algorithm and artificial neural network.
AB - An artificial neural network (ANN) and affinity propagation (AP) algorithm based
user categorization technique is presented. The proposed algorithm is designed
for closed access femtocell network. ANN is used for user classification process
and AP algorithm is used to optimize the ANN training process. AP selects the
best possible training samples for faster ANN training cycle. The users are
distinguished by using the difference of received signal strength in a
multielement femtocell device. A previously developed directive microstrip
antenna is used to configure the femtocell device. Simulation results show that,
for a particular house pattern, the categorization technique without AP algorithm
takes 5 indoor users and 10 outdoor users to attain an error-free operation.
While integrating AP algorithm with ANN, the system takes 60% less training
samples reducing the training time up to 50%. This procedure makes the femtocell
more effective for closed access operation.
PMID- 25133215
TI - A parametric study of nonlinear seismic response analysis of transmission line
structures.
AB - A parametric study of nonlinear seismic response analysis of transmission line
structures subjected to earthquake loading is studied in this paper. The
transmission lines are modeled by cable element which accounts for the
nonlinearity of the cable based on a real project. Nonuniform ground motions are
generated using a stochastic approach based on random vibration analysis. The
effects of multicomponent ground motions, correlations among multicomponent
ground motions, wave travel, coherency loss, and local site on the responses of
the cables are investigated using nonlinear time history analysis method,
respectively. The results show the multicomponent seismic excitations should be
considered, but the correlations among multicomponent ground motions could be
neglected. The wave passage effect has a significant influence on the responses
of the cables. The change of the degree of coherency loss has little influence on
the response of the cables, but the responses of the cables are affected
significantly by the effect of coherency loss. The responses of the cables change
little with the degree of the difference of site condition changing. The effect
of multicomponent ground motions, wave passage, coherency loss, and local site
should be considered for the seismic design of the transmission line structures.
PMID- 25133216
TI - Effects of soil temperature, flooding, and organic matter addition on N2O
emissions from a soil of Hongze Lake wetland, China.
AB - The objectives of this study were to test the effects of soil temperature,
flooding, and raw organic matter input on N2O emissions in a soil sampled at
Hongze Lake wetland, Jiangsu Province, China. The treatments studied were-peat
soil (I), peat soil under flooding (II), peat soil plus raw organic matter (III),
and peat soil under flooding plus organic matter. These four treatments were
incubated at 20 degrees C and 35 degrees C. The result showed that temperature
increase could enhance N2O emissions rate and cumulative emissions significantly;
moreover, the flooded soil with external organic matter inputs showed the lowest
cumulative rise in N2O emissions due to temperature increment. Flooding might
inhibit soil N2O emissions, and the inhibition was more pronounced after organic
matter addition to the original soil. Conversely, organic matter input explained
lower cumulative N2O emissions under flooding. Our results suggest that complex
interactions between flooding and other environmental factors might appear in
soil N2O emissions. Further studies are needed to understand potential synergies
or antagonisms between environmental factors that control N2O emissions in
wetland soils.
PMID- 25133218
TI - Flavonoids in Juglans regia L. leaves and evaluation of in vitro antioxidant
activity via intracellular and chemical methods.
AB - Flavonoids are rich in Juglans regia L. leaves. They have potent antioxidant
properties, which have been related to regulating immune function and enhancing
anticancer activity. Herein, qualitative and quantitative determination of
flavonoids from J. regia leaves was carried out using high performance liquid
chromatography coupled with tandem mass spectrometry with electrospray ionization
and negative ion detection (HPLC-ESI-MS/MS) by comparison of the retention times
and mass spectral fragments with standard substances or related literatures.
Seventeen compounds were identified and major components are quercetin-3-O
rhamnoside (453.11 MUg/g, dry weight), quercetin-3-O-arabinoside (73.91 MUg/g),
quercetin-3-O-xyloside (70.04 MUg/g), kaempferol-O-pentoside derivative (49.04
MUg/g), quercetin-3-O-galactoside (48.61 MUg/g), and kaempferol-O-pentoside
(48.46 MUg/g). The in vitro intracellular antioxidation indicated that flavonoids
from J. regia leaves could reduce the reactive oxygen species (ROS) level in
RAW264.7 cells and showed good radical scavenging activities. These results
proved to be more related to the flavonoids that could be considered in the
design of new formulations of dietary supplements or functional foods.
PMID- 25133219
TI - Multicriteria group decision making by using trapezoidal valued hesitant fuzzy
sets.
AB - The concept of trapezoidal valued hesitant fuzzy set is introduced. Notion for
distance between any two trapezoidal valued hesitant fuzzy elements is given.
Using this proposed distance measure, we extend the technique for order
preference by similarity to ideal solution for trapezoidal valued hesitant fuzzy
sets. An example is constructed to show usefulness of this extension for
multicriteria group decision making, where the opinions about the criteria values
are expressed as trapezoidal valued hesitant fuzzy set.
PMID- 25133217
TI - Comparison of clinical safety and outcomes of early versus delayed laparoscopic
cholecystectomy for acute cholecystitis: a meta-analysis.
AB - OBJECTIVE: To compare the clinical safety and outcomes of early laparoscopic
cholecystectomy versus delayed laparoscopic cholecystectomy for acute
cholecystitis. METHODS: Pertinent studies were selected from the Medline, EMBASE,
and Cochrane library databases, references from published articles, and reviews.
Seven randomized controlled trials (early laparoscopic cholecystectomy versus
delayed laparoscopic cholecystectomy) were selected. Conventional meta-analysis
according to Cochrane Collaboration was used for the pooling of the results.
RESULTS: Seven trials with 1106 patients were included. There was no significant
difference between the two groups in terms of bile duct injury (Peto odds ratio
0.49 (95% confidence interval 0.05 to 4.72); P = 0.54) or conversion to open
cholecystectomy (risk ratio 0.91 (95% confidence interval 0.69 to 1.20); P =
0.50). The total hospital stay was shorter by 4 days for early laparoscopic
cholecystectomy (mean difference -4.12 (95% confidence interval -5.22 to -3.03)
days; P < 0.00001). CONCLUSION: Early laparoscopic cholecystectomy during acute
cholecystitis is safe and shortens the total hospital stay.
PMID- 25133220
TI - New ray tracing method to investigate the various effects on wave propagation in
medical scenario: an application of wireless body area network.
AB - The advent of technology with the increasing use of wireless network has led to
the development of Wireless Body Area Network (WBAN) to continuously monitor the
change of physiological data in a cost efficient manner. As numerous researches
on wave propagation characterization have been done in intrabody communication,
this study has given emphasis on the wave propagation characterization between
the control units (CUs) and wireless access point (AP) in a hospital scenario.
Ray tracing is a tool to predict the rays to characterize the wave propagation.
It takes huge simulation time, especially when multiple transmitters are involved
to transmit physiological data in a realistic hospital environment. Therefore,
this study has developed an accelerated ray tracing method based on the nearest
neighbor cell and prior knowledge of intersection techniques. Beside this, Red
Black tree is used to store and provide a faster retrieval mechanism of objects
in the hospital environment. To prove the superiority, detailed complexity
analysis and calculations of reflection and transmission coefficients are also
presented in this paper. The results show that the proposed method is about 1.51,
2.1, and 2.9 times faster than the Object Distribution Technique (ODT), Space
Volumetric Partitioning (SVP), and Angular Z-Buffer (AZB) methods, respectively.
To show the various effects on received power in 60 GHz frequency, few
comparisons are made and it is found that on average -9.44 dBm, -8.23 dBm, and
9.27 dBm received power attenuations should be considered when human, AP, and CU
move in a given hospital scenario.
PMID- 25133221
TI - Prediction of the reference evapotranspiration using a chaotic approach.
AB - Evapotranspiration is one of the most important hydrological variables in the
context of water resources management. An attempt was made to understand and
predict the dynamics of reference evapotranspiration from a nonlinear dynamical
perspective in this study. The reference evapotranspiration data was calculated
using the FAO Penman-Monteith equation with the observed daily meteorological
data for the period 1966-2005 at four meteorological stations (i.e., Baotou,
Zhangbei, Kaifeng, and Shaoguan) representing a wide range of climatic conditions
of China. The correlation dimension method was employed to investigate the
chaotic behavior of the reference evapotranspiration series. The existence of
chaos in the reference evapotranspiration series at the four different locations
was proved by the finite and low correlation dimension. A local approximation
approach was employed to forecast the daily reference evapotranspiration series.
Low root mean square error (RSME) and mean absolute error (MAE) (for all
locations lower than 0.31 and 0.24, resp.), high correlation coefficient (CC),
and modified coefficient of efficiency (for all locations larger than 0.97 and
0.8, resp.) indicate that the predicted reference evapotranspiration agrees well
with the observed one. The encouraging results indicate the suitableness of
chaotic approach for understanding and predicting the dynamics of the reference
evapotranspiration.
PMID- 25133222
TI - Node deployment algorithm based on viscous fluid model for wireless sensor
networks.
AB - With the scale expands, traditional deployment algorithms are becoming
increasingly complicated than before, which are no longer fit for sensor
networks. In order to reduce the complexity, we propose a node deployment
algorithm based on viscous fluid model. In wireless sensor networks, sensor nodes
are abstracted as fluid particles. Similar to the diffusion and self-propagation
behavior of fluid particles, sensor nodes realize deployment in unknown region
following the motion rules of fluid. Simulation results show that our algorithm
archives good coverage rate and homogeneity in large-scale sensor networks.
PMID- 25133223
TI - Investigation of antioxidant and hepatoprotective activity of standardized
Curcuma xanthorrhiza rhizome in carbon tetrachloride-induced hepatic damaged
rats.
AB - Curcuma xanthorrhiza (CX) has been used for centuries in traditional system of
medicine to treat several diseases such as hepatitis, liver complaints, and
diabetes. It has been consumed as food supplement and "jamu" as a remedy for
hepatitis. Hence, CX was further explored for its potential as a functional food
for liver related diseases. As such, initiative was taken to evaluate the
antioxidant and hepatoprotective potential of CX rhizome. Antioxidant activity of
the standardized CX fractions was determined using in vitro assays.
Hepatoprotective assay was conducted against carbon tetrachloride- (CCl4-)
induced hepatic damage in rats at doses of 125, 250, and 500 mg/kg of hexane
fraction. Highest antioxidant activity was found in hexane fraction. In the case
of hepatoprotective activity, CX hexane fraction showed significant improvement
in terms of a biochemical liver function, antioxidative liver enzymes, and lipid
peroxidation activity. Good recovery was observed in the treated hepatic tissues
histologically. Hence, the results concluded that CX hexane fraction possessed
prominent hepatoprotective activities which might be due to its in vitro
antioxidant activity. These findings also support the use of CX as a functional
food for hepatitis remedy in traditional medicinal system.
PMID- 25133224
TI - Reliable multihop broadcast protocol with a low-overhead link quality assessment
for ITS based on VANETs in highway scenarios.
AB - Vehicular ad hoc networks (VANETs) have been identified as a key technology to
enable intelligent transport systems (ITS), which are aimed to radically improve
the safety, comfort, and greenness of the vehicles in the road. However, in order
to fully exploit VANETs potential, several issues must be addressed. Because of
the high dynamic of VANETs and the impairments in the wireless channel, one key
issue arising when working with VANETs is the multihop dissemination of broadcast
packets for safety and infotainment applications. In this paper a reliable low
overhead multihop broadcast (RLMB) protocol is proposed to address the well-known
broadcast storm problem. The proposed RLMB takes advantage of the hello messages
exchanged between the vehicles and it processes such information to intelligently
select a relay set and reduce the redundant broadcast. Additionally, to reduce
the hello messages rate dependency, RLMB uses a point-to-zone link evaluation
approach. RLMB performance is compared with one of the leading multihop broadcast
protocols existing to date. Performance metrics show that our RLMB solution
outperforms the leading protocol in terms of important metrics such as packet
dissemination ratio, overhead, and delay.
PMID- 25133225
TI - A memristive hyperchaotic system without equilibrium.
AB - A new memristive system is presented in this paper. The peculiarity of the model
is that it does not display any equilibria and exhibits periodic, chaotic, and
also hyperchaotic dynamics in a particular range of the parameters space. The
behavior of the proposed system is investigated through numerical simulations,
such as phase portraits, Lyapunov exponents, and Poincare sections, and circuital
implementation confirmed the hyperchaotic dynamic.
PMID- 25133226
TI - Some gastrointestinal tract characteristics of Karayaka ram lambs slaughtered at
different weights.
AB - Thirty-one Karayaka ram lambs were slaughtered at different body weights (30 (n =
7), 35 (n = 6), 40 (n = 7), 45 (n = 6), and 50 (n = 5) kg of body weight at
fast) to evaluate the growth of their gastrointestinal tract (GIT)
characteristics, to determine the relationship among slaughter body weight (SBW)
and empty body weight (EBW), whole GIT and segments, and the influence of
slaughter weight on the pH of rumen, jejunum, and cecal contents. The effects of
the SBW on GIT weight (P < 0.05), stomach (P < 0.001), and intestine (P <
0.05), the body length (P < 0.001) and caecum (P < 0.05), and the relative
weights of GIT (P < 0.05), stomach (P < 0.001), and intestine (P < 0.001) were
linear whereas that for the length of intestine were quadratic. The effect of SBW
were quadratic (P < 0.05) on ratios of stomach to GIT weight and intestine
length to intestine weight and rumen pH while, for the intestine to GIT weight
ratio (P < 0.001) and caecum pH (P < 0.05), this effect was linear. The results
indicated that for all parameters studied, with the exception of intestinal
length and cecal pH, linear relationships were observed with SBW indicating
steady growth rates for these tissues.
PMID- 25133227
TI - Online handwritten signature verification using neural network classifier based
on principal component analysis.
AB - One of the main difficulties in designing online signature verification (OSV)
system is to find the most distinctive features with high discriminating
capabilities for the verification, particularly, with regard to the high
variability which is inherent in genuine handwritten signatures, coupled with the
possibility of skilled forgeries having close resemblance to the original
counterparts. In this paper, we proposed a systematic approach to online
signature verification through the use of multilayer perceptron (MLP) on a subset
of principal component analysis (PCA) features. The proposed approach illustrates
a feature selection technique on the usually discarded information from PCA
computation, which can be significant in attaining reduced error rates. The
experiment is performed using 4000 signature samples from SIGMA database, which
yielded a false acceptance rate (FAR) of 7.4% and a false rejection rate (FRR) of
6.4%.
PMID- 25133228
TI - Part-based visual tracking via online weighted P-N learning.
AB - We propose a novel part-based tracking algorithm using online weighted P-N
learning. An online weighted P-N learning method is implemented via considering
the weight of samples during classification, which improves the performance of
classifier. We apply weighted P-N learning to track a part-based target model
instead of whole target. In doing so, object is segmented into fragments and
parts of them are selected as local feature blocks (LFBs). Then, the weighted P-N
learning is employed to train classifier for each local feature block (LFB). Each
LFB is tracked through the corresponding classifier, respectively. According to
the tracking results of LFBs, object can be then located. During tracking
process, to solve the issues of occlusion or pose change, we use a substitute
strategy to dynamically update the set of LFB, which makes our tracker robust.
Experimental results demonstrate that the proposed method outperforms the state
of-the-art trackers.
PMID- 25133229
TI - Greenhouse gas emissions from cotton field under different irrigation methods and
fertilization regimes in arid northwestern China.
AB - Drip irrigation is broadly extended in order to save water in the arid cotton
production region of China. Biochar is thought to be a useful soil amendment to
reduce greenhouse gas (GHG) emissions. Here, a field study was conducted to
compare the emissions of nitrous oxide (N2O) and methane (CH4) under different
irrigation methods (drip irrigation (D) and furrow irrigation (F)) and
fertilization regimes (conventional fertilization (C) and conventional
fertilization + biochar (B)) during the cotton growth season. The accumulated N2O
emissions were significantly lower with FB, DC, and DB than with FC by 28.8%,
36.1%, and 37.6%, while accumulated CH4 uptake was 264.5%, 226.7%, and 154.2%
higher with DC, DB, and FC than that with FB, respectively. Irrigation methods
showed a significant effect on total global warming potential (GWP) and yield
scaled GWP (P < 0.01). DC and DB showed higher cotton yield, water use efficiency
(WUE), and lower yield-scaled GWP, as compared with FC and FB. This suggests that
in northwestern China mulched-drip irrigation should be a better approach to
increase cotton yield with depressed GHG. In addition, biochar addition increased
CH4 emissions while it decreased N2O emissions.
PMID- 25133230
TI - Simple BiCMOS CCCTA design and resistorless analog function realization.
AB - The simple realization of the current-controlled conveyor transconductance
amplifier (CCCTA) in BiCMOS technology is introduced. The proposed BiCMOS CCCTA
realization is based on the use of differential pair and basic current mirror,
which results in simple structure. Its characteristics, that is, parasitic
resistance (R x) and current transfer (i o/i z), are also tunable electronically
by external bias currents. The realized circuit is suitable for fabrication using
standard 0.35 MUm BiCMOS technology. Some simple and compact resistorless
applications employing the proposed CCCTA as active elements are also suggested,
which show that their circuit characteristics with electronic controllability are
obtained. PSPICE simulation results demonstrating the circuit behaviors and
confirming the theoretical analysis are performed.
PMID- 25133231
TI - Cyclic soft groups and their applications on groups.
AB - In crisp environment the notions of order of group and cyclic group are well
known due to many applications. In this paper, we introduce order of the soft
groups, power of the soft sets, power of the soft groups, and cyclic soft group
on a group. We also investigate the relationship between cyclic soft groups and
classical groups.
PMID- 25133232
TI - An efficient approach to obtain optimal load factors for structural design.
AB - An efficient optimization approach is described to calibrate load factors used
for designing of structures. The load factors are calibrated so that the
structural reliability index is as close as possible to a target reliability
value. The optimization procedure is applied to find optimal load factors for
designing of structures in accordance with the new version of the Mexico City
Building Code (RCDF). For this aim, the combination of factors corresponding to
dead load plus live load is considered. The optimal combination is based on a
parametric numerical analysis of several reinforced concrete elements, which are
designed using different load factor values. The Monte Carlo simulation technique
is used. The formulation is applied to different failure modes: flexure, shear,
torsion, and compression plus bending of short and slender reinforced concrete
elements. Finally, the structural reliability corresponding to the optimal load
combination proposed here is compared with that corresponding to the load
combination recommended by the current Mexico City Building Code.
PMID- 25133233
TI - Effect of temperature shock and inventory surprises on natural gas and heating
oil futures returns.
AB - The aim of this paper is to examine the impact of temperature shock on both near
month and far-month natural gas and heating oil futures returns by extending the
weather and storage models of the previous study. Several notable findings from
the empirical studies are presented. First, the expected temperature shock
significantly and positively affects both the near-month and far-month natural
gas and heating oil futures returns. Next, significant temperature shock has
effect on both the conditional mean and volatility of natural gas and heating oil
prices. The results indicate that expected inventory surprises significantly and
negatively affects the far-month natural gas futures returns. Moreover,
volatility of natural gas futures returns is higher on Thursdays and that of near
month heating oil futures returns is higher on Wednesdays than other days.
Finally, it is found that storage announcement for natural gas significantly
affects near-month and far-month natural gas futures returns. Furthermore, both
natural gas and heating oil futures returns are affected more by the weighted
average temperature reported by multiple weather reporting stations than that
reported by a single weather reporting station.
PMID- 25133235
TI - Event-based user classification in Weibo media.
AB - Weibo media, known as the real-time microblogging services, has attracted massive
attention and support from social network users. Weibo platform offers an
opportunity for people to access information and changes the way people acquire
and disseminate information significantly. Meanwhile, it enables people to
respond to the social events in a more convenient way. Much of the information in
Weibo media is related to some events. Users who post different contents, and
exert different behavior or attitude may lead to different contribution to the
specific event. Therefore, classifying the large amount of uncategorized social
circles generated in Weibo media automatically from the perspective of events has
been a promising task. Under this circumstance, in order to effectively organize
and manage the huge amounts of users, thereby further managing their contents, we
address the task of user classification in a more granular, event-based approach
in this paper. By analyzing real data collected from Sina Weibo, we investigate
the Weibo properties and utilize both content information and social network
information to classify the numerous users into four primary groups: celebrities,
organizations/media accounts, grassroots stars, and ordinary individuals. The
experiments results show that our method identifies the user categories
accurately.
PMID- 25133234
TI - Protein binding site prediction by combining hidden Markov support vector machine
and profile-based propensities.
AB - Identification of protein binding sites is critical for studying the function of
the proteins. In this paper, we proposed a method for protein binding site
prediction, which combined the order profile propensities and hidden Markov
support vector machine (HM-SVM). This method employed the sequential labeling
technique to the field of protein binding site prediction. The input features of
HM-SVM include the profile-based propensities, the Position-Specific Score Matrix
(PSSM), and Accessible Surface Area (ASA). When tested on different data sets,
the proposed method showed promising results, and outperformed some closely
relative methods by more than 10% in terms of AUC.
PMID- 25133236
TI - Fuzzy-based trust prediction model for routing in WSNs.
AB - The cooperative nature of multihop wireless sensor networks (WSNs) makes it
vulnerable to varied types of attacks. The sensitive application environments and
resource constraints of WSNs mandate the requirement of lightweight security
scheme. The earlier security solutions were based on historical behavior of
neighbor but the security can be enhanced by predicting the future behavior of
the nodes in the network. In this paper, we proposed a fuzzy-based trust
prediction model for routing (FTPR) in WSNs with minimal overhead in regard to
memory and energy consumption. FTPR incorporates a trust prediction model that
predicts the future behavior of the neighbor based on the historical behavior,
fluctuations in trust value over a period of time, and recommendation
inconsistency. In order to reduce the control overhead, FTPR received
recommendations from a subset of neighbors who had maximum number of interactions
with the requestor. Theoretical analysis and simulation results of FTPR protocol
demonstrate higher packet delivery ratio, higher network lifetime, lower end-to
end delay, and lower memory and energy consumption than the traditional and
existing trust-based routing schemes.
PMID- 25133237
TI - Capacitance-based frequency adjustment of micro piezoelectric vibration
generator.
AB - Micro piezoelectric vibration generator has a wide application in the field of
microelectronics. Its natural frequency is unchanged after being manufactured.
However, resonance cannot occur when the natural frequencies of a piezoelectric
generator and the source of vibration frequency are not consistent. Output
voltage of the piezoelectric generator will sharply decline. It cannot normally
supply power for electronic devices. In order to make the natural frequency of
the generator approach the frequency of vibration source, the capacitance FM
technology is adopted in this paper. Different capacitance FM schemes are
designed by different locations of the adjustment layer. The corresponding
capacitance FM models have been established. Characteristic and effect of the
capacitance FM have been simulated by the FM model. Experimental results show
that the natural frequency of the generator could vary from 46.5 Hz to 42.4 Hz
when the bypass capacitance value increases from 0 nF to 30 nF. The natural
frequency of a piezoelectric vibration generator could be continuously adjusted
by this method.
PMID- 25133238
TI - Functioning of women with migraine headaches.
AB - BACKGROUND: Migraines are one of the most commonly occurring ailments affecting
the nervous system. The aim of this research paper was to evaluate the effect
migraines have on the everyday functioning of women. METHOD: The study involved
women with diagnosed migraine headaches (IHS-2004) undergoing treatment at a
neurological clinic. In order to evaluate the influence of headaches on the
everyday functioning of women, a MSQ v.2 questionnaire was used, whereas pain
severity was assessed on a linear VAS scale. RESULTS: Among the clinical factors,
the most influential was the frequency of headaches. Headache duration was
particularly significant for women below the age of 40. Pain severity cited at 8
10 pts on the VAS significantly disrupted and limited everyday functioning. On
the emotional function subscale, the most influential factors were age,
education, and the frequency of headaches. CONCLUSIONS: On account of headache
frequency emerging as the most significant influencing factor, it is of the
utmost importance to inform patients of the value of taking prophylactic
measures. Central to this is the identification of factors that trigger the onset
of migraines. This approach would greatly aid the individual in choosing the
appropriate treatment, either pharmacological or others.
PMID- 25133239
TI - Effects of dimethylaminoethanol and compound amino acid on D-galactose induced
skin aging model of rat.
AB - A lasting dream of human beings is to reverse or postpone aging. In this study,
dimethylaminoethanol (DMAE) and compound amino acid (AA) in Mesotherapy were
investigated for their potential antiaging effects on D-galactose induced aging
skin. At 18 days after D-gal induction, each rat was treated with intradermal
microinjection of saline, AA, 0.1% DMAE, 0.2% DMAE, 0.1% DMAE + AA, or 0.2% DMAE
+ AA, respectively. At 42 days after treatment, the skin wound was harvested and
assayed. Measurement of epidermal and dermal thickness in 0.1% DMAE + AA and 0.2%
DMAE + AA groups appeared significantly thicker than aging control rats. No
differences were found in tissue water content among groups. Hydroxyproline in
0.1% DMAE + AA, 0.2% DMAE + AA, and sham control groups was much higher than all
other groups. Collagen type I, type III, and MMP-1 expression was highly
upregulated in both 0.1% DMAE + AA and 0.2% DMAE + AA groups compared with aging
control. In contrast, TIMP-1 expression levels of various aging groups were
significantly reduced when compared to sham control. Coinjection of DMAE and AA
into target tissue has marked antiaging effects on D-galactose induced skin aging
model of rat.
PMID- 25133240
TI - Modelling hydrology of a single bioretention system with HYDRUS-1D.
AB - A study was carried out on the effectiveness of bioretention systems to abate
stormwater using computer simulation. The hydrologic performance was simulated
for two bioretention cells using HYDRUS-1D, and the simulation results were
verified by field data of nearly four years. Using the validated model, the
optimization of design parameters of rainfall return period, filter media depth
and type, and surface area was discussed. And the annual hydrologic performance
of bioretention systems was further analyzed under the optimized parameters. The
study reveals that bioretention systems with underdrains and impervious
boundaries do have some detention capability, while their total water retention
capability is extremely limited. Better detention capability is noted for smaller
rainfall events, deeper filter media, and design storms with a return period
smaller than 2 years, and a cost-effective filter media depth is recommended in
bioretention design. Better hydrologic effectiveness is achieved with a higher
hydraulic conductivity and ratio of the bioretention surface area to the
catchment area, and filter media whose conductivity is between the conductivity
of loamy sand and sandy loam, and a surface area of 10% of the catchment area is
recommended. In the long-term simulation, both infiltration volume and
evapotranspiration are critical for the total rainfall treatment in bioretention
systems.
PMID- 25133241
TI - A single-phase embedded Z-source DC-AC inverter.
AB - In the conventional DC-AC inverter consisting of two DC-DC converters with
unipolar output capacitors, the output capacitor voltages of the DC-DC converters
must be higher than the DC input voltage. To overcome this weakness, this paper
proposes a single-phase DC-AC inverter consisting of two embedded Z-source
converters with bipolar output capacitors. The proposed inverter is composed of
two embedded Z-source converters with a common DC source and output AC load.
Though the output capacitor voltages of the converters are relatively low
compared to those of a conventional inverter, an equivalent level of AC output
voltages can be obtained. Moreover, by controlling the output capacitor voltages
asymmetrically, the AC output voltage of the proposed inverter can be higher than
the DC input voltage. To verify the validity of the proposed inverter,
experiments were performed with a DC source voltage of 38 V. By controlling the
output capacitor voltages of the converters symmetrically or asymmetrically, the
proposed inverter can produce sinusoidal AC output voltages. The experiments show
that efficiencies of up to 95% and 97% can be achieved with the proposed inverter
using symmetric and asymmetric control, respectively.
PMID- 25133242
TI - A novel method for functional annotation prediction based on combination of
classification methods.
AB - Automated protein function prediction defines the designation of functions of
unknown protein functions by using computational methods. This technique is
useful to automatically assign gene functional annotations for undefined
sequences in next generation genome analysis (NGS). NGS is a popular research
method since high-throughput technologies such as DNA sequencing and microarrays
have created large sets of genes. These huge sequences have greatly increased the
need for analysis. Previous research has been based on the similarities of
sequences as this is strongly related to the functional homology. However, this
study aimed to designate protein functions by automatically predicting the
function of the genome by utilizing InterPro (IPR), which can represent the
properties of the protein family and groups of the protein function. Moreover, we
used gene ontology (GO), which is the controlled vocabulary used to
comprehensively describe the protein function. To define the relationship between
IPR and GO terms, three pattern recognition techniques have been employed under
different conditions, such as feature selection and weighted value, instead of a
binary one.
PMID- 25133243
TI - A new solution to the matrix equation X - AXB = C.
AB - We investigate the matrix equation X - AXB = C. For convenience, the matrix
equation X - AXB = C is named as Kalman-Yakubovich-conjugate matrix equation. The
explicit solution is constructed when the above matrix equation has unique
solution. And this solution is stated as a polynomial of coefficient matrices of
the matrix equation. Moreover, the explicit solution is also expressed by the
symmetric operator matrix, controllability matrix, and observability matrix. The
proposed approach does not require the coefficient matrices to be in arbitrary
canonical form. At the end of this paper, the numerical example is shown to
illustrate the effectiveness of the proposed method.
PMID- 25133244
TI - Effect of zirconium oxide nanofiller and dibutyl phthalate plasticizer on ionic
conductivity and optical properties of solid polymer electrolyte.
AB - New solid polymer electrolytes (SPE) based on poly(ethylene oxide) (PEO) doped
with lithium trifluoromethanesulfonate (LiCF3SO3), dibutyl phthalate (DBP)
plasticizer, and zirconium oxide (ZrO2) nanoparticles were prepared by solution
casting technique. The conductivity was enhanced by addition of dibutyl phthalate
(DBP) plasticizer and ZrO2 nanofiller with maximum conductivity (1.38 * 10(-4)
Scm(-1)). The absorption edge and band gap values showed decreases upon addition
of LiSO3CF3, DBP, and ZrO2 due to the formation of localized states in the SPE
and the degree of disorder in the films increased.
PMID- 25133245
TI - Design and realization of a planar ultrawideband antenna with notch band at 3.5
GHz.
AB - A small antenna with single notch band at 3.5 GHz is designed for ultrawideband
(UWB) communication applications. The fabricated antenna comprises a radiating
monopole element and a perfectly conducting ground plane with a wide slot. To
achieve a notch band at 3.5 GHz, a parasitic element has been inserted in the
same plane of the substrate along with the radiating patch. Experimental results
shows that, by properly adjusting the position of the parasitic element, the
designed antenna can achieve an ultrawide operating band of 3.04 to 11 GHz with a
notched band operating at 3.31-3.84 GHz. Moreover, the proposed antenna achieved
a good gain except at the notched band and exhibits symmetric radiation patterns
throughout the operating band. The prototype of the proposed antenna possesses a
very compact size and uses simple structures to attain the stop band
characteristic with an aim to lessen the interference between UWB and worldwide
interoperability for microwave access (WiMAX) band.
PMID- 25133247
TI - Dynamic finite element analysis of mobile bearing type knee prosthesis under deep
flexional motion.
AB - The primary objective of this study is to distinguish between mobile bearing and
fixed bearing posterior stabilized knee prostheses in the mechanics performance
using the finite element simulation. Quantifying the relative mechanics
attributes and survivorship between the mobile bearing and the fixed bearing
prosthesis remains in investigation among researchers. In the present study, 3
dimensional computational model of a clinically used mobile bearing PS type knee
prosthesis was utilized to develop a finite element and dynamic simulation model.
Combination of displacement and force driven knee motion was adapted to simulate
a flexion motion from 0 degrees to 135 degrees with neutral, 10 degrees , and
20 degrees internal tibial rotation to represent deep knee bending. Introduction
of the secondary moving articulation in the mobile bearing knee prosthesis has
been found to maintain relatively low shear stress during deep knee motion with
tibial rotation.
PMID- 25133246
TI - Genome wide analysis of sex difference in gene expression profiles of bone
formations using sfx mice and BXD RI strains.
AB - The objective of this study is to identify sex differentially expressed genes in
bone using a mouse model of spontaneous fracture, sfx, which lacks the gene for L
gulonolactone oxidase (Gulo), a key enzyme in the ascorbic acid (AA) synthesis
pathway. We first identified the genes that are differentially expressed in the
femur between female and male in sfx mice. We then analyzed the potential gene
network among those differentially expressed genes with whole genome expression
profiles generated using spleens of female and male mice of a total of 67 BXD
(C57BL/6J X DBA/2J) recombinant inbred (RI) and other strains. Our result
indicated that there was a sex difference in the whole genome profiles in sfx
mice as measured by the proportion of up- and downregulated genes. Several genes
in the pathway of bone development are differentially expressed between the male
and female of sfx mice. Comparison of gene network of up- and downregulated bone
relevant genes also suggests a sex difference.
PMID- 25133248
TI - Automated long-term monitoring of parallel microfluidic operations applying a
machine vision-assisted positioning method.
AB - As microfluidics has been applied extensively in many cell and biochemical
applications, monitoring the related processes is an important requirement. In
this work, we design and fabricate a high-throughput microfluidic device which
contains 32 microchambers to perform automated parallel microfluidic operations
and monitoring on an automated stage of a microscope. Images are captured at
multiple spots on the device during the operations for monitoring samples in
microchambers in parallel; yet the device positions may vary at different time
points throughout operations as the device moves back and forth on a motorized
microscopic stage. Here, we report an image-based positioning strategy to realign
the chamber position before every recording of microscopic image. We fabricate
alignment marks at defined locations next to the chambers in the microfluidic
device as reference positions. We also develop image processing algorithms to
recognize the chamber positions in real-time, followed by realigning the chambers
to their preset positions in the captured images. We perform experiments to
validate and characterize the device functionality and the automated realignment
operation. Together, this microfluidic realignment strategy can be a platform
technology to achieve precise positioning of multiple chambers for general
microfluidic applications requiring long-term parallel monitoring of cell and
biochemical activities.
PMID- 25133249
TI - Investigation of a novel common subexpression elimination method for low power
and area efficient DCT architecture.
AB - A wide interest has been observed to find a low power and area efficient hardware
design of discrete cosine transform (DCT) algorithm. This research work proposed
a novel Common Subexpression Elimination (CSE) based pipelined architecture for
DCT, aimed at reproducing the cost metrics of power and area while maintaining
high speed and accuracy in DCT applications. The proposed design combines the
techniques of Canonical Signed Digit (CSD) representation and CSE to implement
the multiplier-less method for fixed constant multiplication of DCT coefficients.
Furthermore, symmetry in the DCT coefficient matrix is used with CSE to further
decrease the number of arithmetic operations. This architecture needs a single
port memory to feed the inputs instead of multiport memory, which leads to
reduction of the hardware cost and area. From the analysis of experimental
results and performance comparisons, it is observed that the proposed scheme uses
minimum logic utilizing mere 340 slices and 22 adders. Moreover, this design
meets the real time constraints of different video/image coders and peak-signal
to-noise-ratio (PSNR) requirements. Furthermore, the proposed technique has
significant advantages over recent well-known methods along with accuracy in
terms of power reduction, silicon area usage, and maximum operating frequency by
41%, 15%, and 15%, respectively.
PMID- 25133250
TI - Structural health monitoring of civil infrastructure using optical fiber sensing
technology: a comprehensive review.
AB - In the last two decades, a significant number of innovative sensing systems based
on optical fiber sensors have been exploited in the engineering community due to
their inherent distinctive advantages such as small size, light weight, immunity
to electromagnetic interference (EMI) and corrosion, and embedding capability. A
lot of optical fiber sensor-based monitoring systems have been developed for
continuous measurement and real-time assessment of diversified engineering
structures such as bridges, buildings, tunnels, pipelines, wind turbines, railway
infrastructure, and geotechnical structures. The purpose of this review article
is devoted to presenting a summary of the basic principles of various optical
fiber sensors, innovation in sensing and computational methodologies, development
of novel optical fiber sensors, and the practical application status of the
optical fiber sensing technology in structural health monitoring (SHM) of civil
infrastructure.
PMID- 25133252
TI - 50 MHz-10 GHz low-power resistive feedback current-reuse mixer with inductive
peaking for cognitive radio receiver.
AB - A low-power wideband mixer is designed and implemented in 0.13 um standard CMOS
technology based on resistive feedback current-reuse (RFCR) configuration for the
application of cognitive radio receiver. The proposed RFCR architecture
incorporates an inductive peaking technique to compensate for gain roll-off at
high frequency while enhancing the bandwidth. A complementary current-reuse
technique is used between transconductance and IF stages to boost the conversion
gain without additional power consumption by reusing the DC bias current of the
LO stage. This downconversion double-balanced mixer exhibits a high and flat
conversion gain (CG) of 14.9 +/- 1.4 dB and a noise figure (NF) better than 12.8
dB. The maximum input 1-dB compression point (P1dB) and maximum input third-order
intercept point (IIP3) are -13.6 dBm and -4.5 dBm, respectively, over the desired
frequency ranging from 50 MHz to 10 GHz. The proposed circuit operates down to a
supply headroom of 1 V with a low-power consumption of 3.5 mW.
PMID- 25133251
TI - Highly effective ex vivo gene manipulation to study kidney development using self
complementary adenoassociated viruses.
AB - BACKGROUND: Ex vivo culture of intact embryonic kidney has become a powerful
system for studying renal development. However, few methods have been available
for gene manipulation and have impeded the identification and investigation of
genes in this developmental process. RESULTS: Here we systemically compared eight
different serotypes of pseudotyped self-complementary adenoassociated viruses
(scAAVs) transduction in cultured embryonic kidney with a modified culture
procedure. We demonstrated that scAAV was highly effective in delivering genes
into and expressing in compacted tissues. scAAV serotypes 2 and 8 exhibited
higher efficiency of transduction compared to others. Expression kinetics assay
revealed that scAAV can be used for gene manipulation at the study of UB
branching and nephrogenesis. Repressing WT1 in cultured kidney using shRNA
impairs tubule formation. We for the first time employed and validated scAAV as a
gene delivery tool in cultured kidney. CONCLUSIONS: These findings are expected
to expedite the use of the ex vivo embryonic kidney cultures for kidney
development research. For other ex vivo cultured organ models, scAAV could also
be a promising tool for organogenesis study.
PMID- 25133253
TI - Video texture synthesis based on flow-like stylization painting.
AB - The paper presents an NP-video rendering system based on natural phenomena. It
provides a simple nonphotorealistic video synthesis system in which user can
obtain a flow-like stylization painting and infinite video scene. Firstly, based
on anisotropic Kuwahara filtering in conjunction with line integral convolution,
the phenomena video scene can be rendered to flow-like stylization painting.
Secondly, the methods of frame division, patches synthesis, will be used to
synthesize infinite playing video. According to selection examples from different
natural video texture, our system can generate stylized of flow-like and infinite
video scenes. The visual discontinuities between neighbor frames are decreased,
and we also preserve feature and details of frames. This rendering system is easy
and simple to implement.
PMID- 25133254
TI - Design and performance evaluation of a distributed OFDMA-based MAC protocol for
MANETs.
AB - In this paper, we propose a distributed MAC protocol for OFDMA-based wireless
mobile ad hoc multihop networks, in which the resource reservation and data
transmission procedures are operated in a distributed manner. A frame format is
designed considering the characteristics of OFDMA that each node can transmit or
receive data to or from multiple nodes simultaneously. Under this frame
structure, we propose a distributed resource management method including network
state estimation and resource reservation processes. We categorize five types of
logical errors according to their root causes and show that two of the logical
errors are inevitable while three of them are avoided under the proposed
distributed MAC protocol. In addition, we provide a systematic method to
determine the advertisement period of each node by presenting a clear relation
between the accuracy of estimated network states and the signaling overhead. We
evaluate the performance of the proposed protocol in respect of the reservation
success rate and the success rate of data transmission. Since our method focuses
on avoiding logical errors, it could be easily placed on top of the other
resource allocation methods focusing on the physical layer issues of the resource
management problem and interworked with them.
PMID- 25133255
TI - Method to eliminate flux linkage DC component in load transformer for static
transfer switch.
AB - Many industrial and commercial sensitive loads are subject to the voltage sags
and interruptions. The static transfer switch (STS) based on the thyristors is
applied to improve the power quality and reliability. However, the transfer will
result in severe inrush current in the load transformer, because of the DC
component in the magnetic flux generated in the transfer process. The inrush
current which is always 2 ~ 30 p.u. can cause the disoperation of relay
protective devices and bring potential damage to the transformer. The way to
eliminate the DC component is to transfer the related phases when the residual
flux linkage of the load transformer and the prospective flux linkage of the
alternate source are equal. This paper analyzes how the flux linkage of each
winding in the load transformer changes in the transfer process. Based on the
residual flux linkage when the preferred source is completely disconnected, the
method to calculate the proper time point to close each phase of the alternate
source is developed. Simulation and laboratory experiments results are presented
to show the effectiveness of the transfer method.
PMID- 25133256
TI - On the generalization of Lehmer problem and high-dimension Kloosterman sums.
AB - For any fixed integer k >= 2 and integer r with (r, p) = 1, it is clear that
there exist k integers 1 <= a i <= p - 1(i = 1, 2, ..., k) such that a 1 a 2 ? a
k = r mod p. Let N(k, r; p) denote the number of all (a 1, a 2, ? a k ) such that
a 1 a 2 ? a k = r mod p and 2?(a 1 + a 2 + ? + a k ). In this paper, we will use
the analytic method and the estimate for high-dimension Kloosterman sums to study
the asymptotic properties of N(k, r; p) and give two interesting asymptotic
formulae for it.
PMID- 25133257
TI - Mathematical model relating uniaxial compressive behavior of manufactured sand
mortar to MIP-derived pore structure parameters.
AB - The uniaxial compression response of manufactured sand mortars proportioned using
different water-cement ratio and sand-cement ratio is examined. Pore structure
parameters such as porosity, threshold diameter, mean diameter, and total amounts
of macropores, as well as shape and size of micropores are quantified by using
mercury intrusion porosimetry (MIP) technique. Test results indicate that strains
at peak stress and compressive strength decreased with the increasing sand-cement
ratio due to insufficient binders to wrap up entire sand. A compression stress
strain model of normal concrete extending to predict the stress-strain
relationships of manufactured sand mortar is verified and agreed well with
experimental data. Furthermore, the stress-strain model constant is found to be
influenced by threshold diameter, mean diameter, shape, and size of micropores. A
mathematical model relating stress-strain model constants to the relevant pore
structure parameters of manufactured sand mortar is developed.
PMID- 25133258
TI - Cost-benefit analysis and emission reduction of energy efficient lighting at the
Universiti Tenaga Nasional.
AB - This paper reports the result of an investigation on the potential energy saving
of the lighting systems at selected buildings of the Universiti Tenaga Nasional.
The scope of this project includes evaluation of the lighting system in the
Library, Admin Building, College of Engineering, College of Information
Technology, Apartments, and COE Food court of the university. The main objectives
of this project are to design the proper retrofit scenario and to calculate the
potential electricity saving, the payback period, and the potential environmental
benefits. In this survey the policy for retrofitting the old lighting system with
the new energy saving LEDs starts with 10% for the first year and continues
constantly for 10 years until all the lighting systems have been replaced. The
result of the life cycle analysis reveals that after four years, the selected
buildings will bring profit for the investment.
PMID- 25133259
TI - Feasibility of using phase change materials to control the heat of hydration in
massive concrete structures.
AB - This paper presents experimental results that can be applied to select a possible
phase change material (PCM), such as a latent heat material (LHM), to control the
hydration heat in mass concrete structures. Five experimental tests
(microconduction, simplified adiabatic temperature rise, heat, and compressive
strength tests) were conducted to select the most desirable LHM out of seven
types of inorganic PCM used in cement mortar and to determine the most suitable
mix design. The results of these experimental tests were used to assess the
feasibility of using PCM to reduce hydration heat in mass concrete that was
examined. The experimental results show that cement mortar containing barium-
[Ba(OH)2 . 8H2O] based PCM has the lowest amount of total hydration heat of the
cement pastes. The barium-based PCM provides good latent heat properties that
help to prevent volume change and microcracks caused by thermal stress in mass
concrete.
PMID- 25133260
TI - Assessment model of ecoenvironmental vulnerability based on improved entropy
weight method.
AB - Assessment of ecoenvironmental vulnerability plays an important role in the
guidance of regional planning, the construction and protection of ecological
environment, which requires comprehensive consideration on regional resources,
environment, ecology, society and other factors. Based on the driving mechanism
and evolution characteristics of ecoenvironmental vulnerability in cold and arid
regions of China, a novel evaluation index system on ecoenvironmental
vulnerability is proposed in this paper. For the disadvantages of conventional
entropy weight method, an improved entropy weight assessment model on
ecoenvironmental vulnerability is developed and applied to evaluate the
ecoenvironmental vulnerability in western Jilin Province of China. The assessing
results indicate that the model is suitable for ecoenvironmental vulnerability
assessment, and it shows more reasonable evaluation criterion, more distinct
insights and satisfactory results combined with the practical conditions. The
model can provide a new method for regional ecoenvironmental vulnerability
evaluation.
PMID- 25133261
TI - The laws of natural deduction in inference by DNA computer.
AB - We present a DNA-based implementation of reaction system with molecules encoding
elements of the propositional logic, that is, propositions and formulas. The
protocol can perform inference steps using, for example, modus ponens and modus
tollens rules and de Morgan's laws. The set of the implemented operations allows
for inference of formulas using the laws of natural deduction. The system can
also detect whether a certain proposition a can be deduced from the basic facts
and given rules. The whole protocol is fully autonomous; that is, after
introducing the initial set of molecules, no human assistance is needed. Only one
restriction enzyme is used throughout the inference process. Unlike some other
similar implementations, our improved design allows representing simultaneously a
fact a and its negation ~a, including special reactions to detect the
inconsistency, that is, a simultaneous occurrence of a fact and its negation. An
analysis of correctness, completeness, and complexity is included.
PMID- 25133262
TI - Light-output enhancement of GaN-based light-emitting diodes with three
dimensional backside reflectors patterned by microscale cone array.
AB - Three-dimensional (3D) backside reflector, compared with flat reflectors, can
improve the probability of finding the escape cone for reflecting lights and thus
enhance the light-extraction efficiency (LEE) for GaN-based light-emitting diode
(LED) chips. A triangle-lattice of microscale SiO2 cone array followed by a 16
pair Ti3O5/SiO2 distributed Bragg reflector (16-DBR) was proposed to be attached
on the backside of sapphire substrate, and the light-output enhancement was
demonstrated by numerical simulation and experiments. The LED chips with flat
reflectors or 3D reflectors were simulated using Monte Carlo ray tracing method.
It is shown that the LEE increases as the reflectivity of backside reflector
increases, and the light-output can be significantly improved by 3D reflectors
compared to flat counterparts. It can also be observed that the LEE decreases as
the refractive index of the cone material increases. The 3D 16-DBR patterned by
microscale SiO2 cone array benefits large enhancement of LEE. This microscale
pattern was prepared by standard photolithography and wet-etching technique.
Measurement results show that the 3D 16-DBR can provide 12.1% enhancement of wall
plug efficiency, which is consistent with the simulated value of 11.73% for the
enhancement of LEE.
PMID- 25133263
TI - Comparative studies on bioactive constituents in hawk tea infusions with
different maturity degree and their antioxidant activities.
AB - Hawk tea (Litsea coreana var. lanuginose) is a very popular herbal tea in the
southwest of China. According to the maturity degree of raw materials, Hawk tea
can usually be divided into three types: Hawk bud tea (HB), Hawk primary leaf tea
(HP), and Hawk mature leaf tea (HM). In this study, some of the bioactive
constituents and antioxidant properties of the three kinds of Hawk tea infusions
were comparatively investigated. The results showed that the contents of total
flavonoids, vitamin C, and carbohydrates in Hawk bud tea infusion (HBI) were
higher than those in Hawk primary leaf tea infusion (HPI) and Hawk mature leaf
tea infusion (HMI). HPI had higher contents of total polyphenols and exhibited
better DPPH radical scavenging activity and ferric reducing activity power. HBI
could provide more effective protection against erythrocyte hemolysis. As age is
going from bud to mature leaf, the ability to inhibit the formation of low
density lipoprotein (LDL) conjugated diene and the loss of tryptophan
fluorescence decreased. The bioactive constituents and antioxidant activities of
Hawk tea infusions were significantly affected by the maturity degree of the raw
material.
PMID- 25133264
TI - Expression profiles of 12 late embryogenesis abundant protein genes from Tamarix
hispida in response to abiotic stress.
AB - Twelve embryogenesis abundant protein (LEA) genes (named ThLEA-1 to -12) were
cloned from Tamarix hispida. The expression profiles of these genes in response
to NaCl, PEG, and abscisic acid (ABA) in roots, stems, and leaves of T. hispida
were assessed using real-time reverse transcriptase-polymerase chain reaction (RT
PCR). These ThLEAs all showed tissue-specific expression patterns in roots,
stems, and leaves under normal growth conditions. However, they shared a high
similar expression patterns in the roots, stems, and leaves when exposed to NaCl
and PEG stress. Furthermore, ThLEA-1, -2, -3, -4, and -11 were induced by NaCl
and PEG, but ThLEA-5, -6, -8, -10, and -12 were downregulated by salt and drought
stresses. Under ABA treatment, some ThLEA genes, such as ThLEA-1, -2, and -3,
were only slightly differentially expressed in roots, stems, and leaves,
indicating that they may be involved in the ABA-independent signaling pathway.
These findings provide a basis for the elucidation of the function of LEA genes
in future work.
PMID- 25133265
TI - A simple quality assessment index for stereoscopic images based on 3D gradient
magnitude.
AB - We present a simple quality assessment index for stereoscopic images based on 3D
gradient magnitude. To be more specific, we construct 3D volume from the
stereoscopic images across different disparity spaces and calculate pointwise 3D
gradient magnitude similarity (3D-GMS) along three horizontal, vertical, and
viewpoint directions. Then, the quality score is obtained by averaging the 3D-GMS
scores of all points in the 3D volume. Experimental results on four publicly
available 3D image quality assessment databases demonstrate that, in comparison
with the most related existing methods, the devised algorithm achieves high
consistency alignment with subjective assessment.
PMID- 25133266
TI - Low power upconversion mixer for medical remote sensing.
AB - This work presents the design of a low power upconversion mixer adapted in
medical remote sensing such as wireless endoscopy application. The proposed
upconversion mixer operates in ISM band of 433 MHz. With the carrier power of -5
dBm, the proposed mixer has an output inferred 1 dB compression point of -0.5 dBm
with a corresponding output third-order intercept point (OIP3) of 7.1 dBm. The
design of the upconversion mixer is realized on CMOS 0.13 MUm platform, with a
current consumption of 594 MUA at supply voltage headroom of 1.2 V.
PMID- 25133267
TI - Differential responses of net ecosystem exchange of carbon dioxide to light and
temperature between spring and neap tides in subtropical mangrove forests.
AB - The eddy flux data with field records of tidal water inundation depths of the
year 2010 from two mangroves forests in southern China were analyzed to
investigate the tidal effect on mangrove carbon cycle. We compared the net
ecosystem exchange (NEE) and its responses to light and temperature,
respectively, between spring tide and neap tide inundation periods. For the most
time of the year 2010, higher daytime NEE values were found during spring tides
than during neap tides at both study sites. Regression analysis of daytime NEE to
photosynthetically active radiation (PAR) using the Landsberg model showed
increased sensitivity of NEE to PAR with higher maximum photosynthetic rate
during spring tides than neap tides. In contrast, the light compensation points
acquired from the regression function of the Landsberg model were smaller during
spring tides than neap tides in most months. The dependence of nighttime NEE on
soil temperature was lower under spring tide than under neap tides. All these
results above indicated that ecosystem carbon uptake rates of mangrove forests
were strengthened, while ecosystem respirations were inhibited during spring
tides in comparison with those during neap tides, which needs to be considered in
modeling mangrove ecosystem carbon cycle under future sea level rise scenarios.
PMID- 25133268
TI - Antihepatoma activity of Artocarpus communis is higher in fractions with high
artocarpin content.
AB - Extracts from natural plants have been used in traditional medicine for many
centuries worldwide. Artocarpus communis is one such plant that has been used to
treat liver cirrhosis, hypertension, and diabetes. To our knowledge, this study
is the first to investigate the antihepatoma activity of A. communis toward HepG2
and PLC/PRF/5 cells and the first to explore the relationship between
antihepatoma activity and the active compound artocarpin content in different
fractions of A. communis. A. communis methanol extract and fractions induced dose
dependent reduction of tumor cell viability. DNA laddering analysis revealed that
A. communis extract and fractions did not induce apoptosis in HepG2 and PLC/PRF/5
cells. Instead, acridine orange staining revealed that A. communis triggered
autophagic cell death in a dose-dependent manner. The antihepatoma activity of A.
communis is attributable to artocarpin. The fractions with the highest artocarpin
content were also the fractions with the highest antihepatoma activity in the
following order: dichloromethane fraction > methanol extract > ethyl acetate
fraction > n-butanol fraction > n-hexane fraction. Taken together, A. communis
showed antihepatoma activity through autophagic cell death. The effect was
related to artocarpin content. Artocarpin could be considered an indicator of the
anticancer potential of A. communis extract.
PMID- 25133269
TI - Influence of the number of adhesive layers on adhesive interface properties under
cariogenic challenge using streptococcus mutans.
AB - PURPOSE: To test the hypothesis that the number of adhesive layers influences the
adhesive interface properties under cariogenic challenge conditions using a
Streptococcus mutans model. MATERIALS AND METHODS: Bovine teeth (n = 90) were
sectioned into blocks of 5 mm and divided into two groups for microleakage
testing (n = 60) and tensile bond strength testing (n = 30). In each group, the
samples were subdivided into subgroups according to the number of adhesive layers
applied on the dentin: one (SB1), two (SB2), and three adhesive layers (SB3). The
samples of the control groups were placed in BHI broth medium supplemented with
2% sucrose without microorganisms, and the experimental groups were submitted to
Streptococcus mutans American Type Culture Collection (ATCC) for 5 days. For the
tensile strength test, samples were sectioned into 1-mm-thick slices and
submitted to a constant load of 0.5 mm/min in a universal testing machine.
Fractured surfaces were analyzed and characterized as adhesive, cohesive, or
mixed. The microleakage test was performed with silver nitrate solution. RESULTS:
In experimental groups, the tensile test revealed a statistically significant
difference between the one- (18.59 +/- 5.3) and three-layer (11.28 +/- 5.0)
groups (p < 0.001; ANOVA and Tukey's test). The adhesive failure mode was
slightly more frequent in the one- (60%) and three-layer (80%) adhesive
application groups. On the other hand, the microleakage levels of all
experimental groups were statistically similar (Kruskal-Wallis; p > 0.05).
CONCLUSION: The experimental conditions influenced tensile properties and failure
modes of different adhesive interfaces; however, they did not influence
microleakage.
PMID- 25133270
TI - Influence of PEEK surface modification on surface properties and bond strength to
veneering resin composites.
AB - PURPOSE: To test the impact of mechanical and chemical treatments of PEEK on
surface roughness (SR), surface free energy (SFE), and tensile bond strength
(TBS) to veneering resin composites. MATERIALS AND METHODS: PEEK specimens (N =
680) were fabricated and divided into treatment groups (n = 170/group): 1. air
abrasion (AIA); 2. etching with piranha solution (PIS); 3. air abrasion + piranha
acid etching (AIP); and 4. no treatment (NO). Ten specimens of each treatment
group were assessed with a contact angle measuring device and profilometer to
determine SFE and SR, respectively. The remaining 160 specimens of each group
were divided into subgroups according to coupling method (n = 32/subgroup): 1.
Monobond Plus/ Heliobond (MH); 2. Visio.link (VL); 3. Clearfil Ceramic Primer
(CCP); 4. Signum PEEK Bond (SPB); and 5. control, no coupling (CG). Specimens
were veneered using Signum Composite/SiCo or Signum Ceramis/SiCe (both: n = 16),
incubated in water (60 days at 37 degrees C) and thermocycled (5000 cycles of 5
degrees C/55 degrees C). TBS was measured and data analyzed by three- and one-way
ANOVA, Kruskal-Wallis and Mann-Whitney tests (p < 0.05). RESULTS: A significant
effect of surface treatment (p < 0.001) and coupling agent application (p <
0.001) on TBS was observed. AIA specimens with/without PIS showed the highest
SFE, SR, and TBS. No differences were measured between PIS and NO, and between
AIA and AIP. When no coupling agent was used, no adhesion was obtained. CCP
resulted in low adhesion values, whereas MH, SPB, and VL exhibited increased TBS.
No significant impact of the veneering resin composite on TBS was found (p =
0.424). CONCLUSION: AIA and AIP combined with VL, SPB, and MH can be recommended
for clinical use.
PMID- 25133271
TI - PI3 kinase enzymology on fluid lipid bilayers.
AB - We report the use of fluid lipid bilayer membrane as a model platform to study
the influence of the bilayer microenvironment and composition on the enzymology
in membrane. As a model system we determined the enzyme kinetics on membranes for
the transformation of bilayers containing phosphoinositol(4,5)-bisphosphate
(PI(4,5)P2) to phosphoinositol(3,4,5)-trisphosphate (PI(3,4,5)P3) by the enzyme
phosphoinositol-3-kinase (PI3K) using radiolabeled ATP. The activity of the
enzyme was monitored as a function of the radioactivity incorporated within the
bilayer. The transformation of PI(4,5)P2 to PI(3,4,5)P3 was determined using a
mass strip assay. The fluidity of the bilayer was confirmed by Fluorescence
Recovery After Photobleaching (FRAP) experiments. Kinetic simulations were
performed based on Langmuir adsorption and Michaelis-Menton kinetics equations to
generate the rate constants for the enzymatic reaction. The effect of cholesterol
on the enzyme kinetics was studied by doping the bilayer with 1% cholesterol.
This leads to significant reduction in reaction rate due to change in membrane
microenvironment. This strategy provides a method to study the enzymology of
various kinases and phosphatases occurring at the membrane and also how these
reactions are affected by the membrane composition and surface microenvironment.
PMID- 25133272
TI - Multiplex single particle analysis in microfluidics.
AB - A straightforward way to measure separated micrometric sized particles in
microfluidic flow is reported. The light scattering profile (LSP) of each single
particle is fully characterized by using a CMOS-camera based small angle light
scattering (SALS) apparatus, ranging from 2 degrees up to 30 degrees . To ensure
controlled particle passage through the incident laser, a viscoelastic 3D
alignment effect by viscoelastic induced particle migration has been implemented
in a simple and cost-effective microfluidic device. Different polystyrene
particle sizes are measured in microfluidic flows and the obtained scattering
signatures are matched with the Lorenz-Mie based scattering theory. The results
confirm the possibility of using this apparatus for real multiplex particle
analyses in microfluidic particle flows.
PMID- 25133274
TI - An asymmetric [3+2] cycloaddition of alkynes with oxiranes by selective C-C bond
cleavage of epoxides: highly efficient synthesis of chiral furan derivatives.
AB - An efficient enantioselective [3+2] cycloaddition of alkynes with oxiranes via
selective C-C bond cleavage of epoxides was developed. A number of optically
active 2,5-dihydrofurans were obtained in excellent yields (up to 99%) and
enantioselectivities (up to 95% ee) under mild reaction conditions. Moreover,
chiral tetrahydrofuran could also be obtained by cycloaddition of alkene and
oxirane or hydrogenation of chiral 2,5-dihydrofuran.
PMID- 25133275
TI - A selective and sensitive fluorescent albumin probe for the determination of
urinary albumin.
AB - In this communication, we report a simple albumin probe based on a fluorescent
molecular rotor for the detection of trace albumin levels in urine. In the
presence of albumin, the probe exhibits remarkable 400-fold fluorescence
enhancement with high selectivity and sensitivity. The probe was successfully
applied in the quantitative detection of urinary albumin.
PMID- 25133273
TI - Desalting protein ions in native mass spectrometry using supercharging reagents.
AB - Effects of the supercharging reagents m-NBA and sulfolane on sodium ion adduction
to protein ions formed using native mass spectrometry were investigated. There is
extensive sodium adduction on protein ions formed by electrospray ionization from
aqueous solutions containing millimolar concentrations of NaCl, which can lower
sensitivity by distributing the signal of a given charge state over multiple
adducted ions and can reduce mass measuring accuracy for large proteins and non
covalent complexes for which individual adducts cannot be resolved. The average
number of sodium ions adducted to the most abundant ion formed from ten small
(8.6-29 kDa) proteins for which adducts can be resolved is reduced by 58% or 80%
on average, respectively, when 1.5% m-NBA or 2.5% sulfolane are added to aqueous
solutions containing sodium compared to without the supercharging reagent.
Sulfolane is more effective than m-NBA at reducing sodium ion adduction and at
preserving non-covalent protein-ligand and protein-protein interactions.
Desalting with 2.5% sulfolane enables detection of several glycosylated forms of
79.7 kDa holo-transferrin and NADH bound to the 146 kDa homotetramer LDH, which
are otherwise unresolved due to peak broadening from extensive sodium adduction.
Although sulfolane is more effective than m-NBA at protein ion desalting, m-NBA
reduces salt clusters at high m/z and can increase the signal-to-noise ratios of
protein ions by reducing chemical noise. Desalting is likely a result of these
supercharging reagents binding sodium ions in solution, thereby reducing the
sodium available to adduct to protein ions.
PMID- 25133277
TI - Ankle-brachial index in patients with ischaemic stroke.
PMID- 25133278
TI - Pure hereditary spastic paraplegia due to a de novo mutation in the NIPA1 gene.
PMID- 25133276
TI - Recombinant murine growth hormone particles are more immunogenic with intravenous
than subcutaneous administration.
AB - Evaluation and mitigation of the risk of immunogenicity to protein aggregates and
particles in therapeutic protein products remains a primary concern for drug
developers and regulatory agencies. To investigate how the presence of protein
particles and the route of administration influence the immunogenicity of a model
therapeutic protein, we measured the immune response in mice to injections of
formulations of recombinant murine growth hormone (rmGH) that contained
controlled levels of protein particles. Mice were injected twice over 6 weeks
with rmGH formulations via the subcutaneous, intraperitoneal, or intravenous
(i.v.) routes. In addition to soluble, monomeric rmGH, the samples prepared
contained either nanoparticles of rmGH or both nano- and microparticles of
rmGH.The appearance of anti-rmGH IgG1, IgG2a, IgG2b, IgG2c, and IgG3 titers
following the second injection of both preparations implies that multiple
mechanisms contributed to the immune response. No dependence of the immune
response on particle size and distribution was observed. The immune response
measured after the second injection was most pronounced when i.v. administration
was used. Despite producing high anti-rmGH titers mice appeared to retain the
ability to properly regulate and use endogenous growth hormone.
PMID- 25133279
TI - Intravenous thrombolysis in stroke patients receiving rivaroxaban.
PMID- 25133280
TI - Paraneoplastic motor neuron disease associated with breast cancer.
PMID- 25133281
TI - Inquiry to inclusion of papers among Turkey's 2012 cardiovascular publications.
Author's reply.
PMID- 25133282
TI - Mean platelet volume may not be related to clopidogrel resistance in patients
with acute coronary syndrome. Author's reply.
PMID- 25133283
TI - Health warnings about obesity: King's Festival of Food and Ideas.
PMID- 25133284
TI - [Cardiovascular magnetic resonance imaging in patients with acute chest pain].
AB - Acute chest pain is a common reason for presentation to the emergency department.
It can be caused by a wide variety of diseases, some of which are potentially
lethal, so it must be diagnosed quickly. The rise of computed tomography to
evaluate patients with acute chest pain is noteworthy. However, computed
tomography is not without limitations in this context. Cardiovascular magnetic
resonance imaging is a potentially useful technique in this group of patients,
although its availability and the time required for examinations restrict its use
to specific indications.
PMID- 25133285
TI - Wnt-signalling: A new direction for alzheimer disease?
PMID- 25133286
TI - Why are cancer drugs so costly?
PMID- 25133287
TI - [Acute perforated eardrum - patching with hyaluronic acid or spontaneous
healing?].
PMID- 25133288
TI - [Lesions of the submandibular glands - contrast-enhanced ultrasound for non
invasive diagnosis].
PMID- 25133289
TI - [Tips & tricks--collar button technique: safe and patient friendly myringoplasty
technique].
AB - Background: The inlay cartilage butterfly myringoplasty is a simple technique
with few complications for closure of tympanic membrane defects introduced by
Eavey 1998, but still not often used. Its advantages consist in avoiding of
exposure the tympanic cavity and possible blunting, option to operate both ears
at once, safe local anaesthesia, reduction of operation time and cost, minimal
postoperative care and patient comfort. Patients and Methods: We operated 10
patients using a to date not described simple cartilage transplant without
perichondrium. Reason, localisation, extent and duration of the defect as well as
complications, patient assessment and pure tone audiogram were analysed. Results:
All defects were closed six months postoperative. Seven patients rated hearing as
improved, two as non-changed and one patient showed deafness in the pure tone
audiogram pre- and postoperative. The average air-bone gap of the thresholds at
frequencies 0.5, 1, 2 and 3 kHz was 8.6 dB postoperative as compared to 16.3 dB
preoperative. It could be shown that pure cartilage transplants without
perichondrium used for defects up to 6mm in diameter were enwrapped by the
tympanic membrane and covered by capillaries. Conclusion: The inlay cartilage
butterfly myringoplasty is a safe and gentle technique for tympanic membrane
defect closure.
PMID- 25133290
TI - Comparison of oxidation resistance of UHMWPE and POM in H2O2 solution from ReaxFF
reactive molecular dynamics simulations.
AB - The oxidation mechanism of ultra-high-molecular-weight polyethylene (UHMWPE) and
polyoxymethylene (POM) in hydrogen peroxide solution was investigated by
molecular dynamics (MD) simulations via reactive force field (ReaxFF) method. MD
results from ReaxFF suggested that UHMWPE provided better antioxidation activity
at high temperature (>373 K) than its POM counterpart in the same concentration
of hydrogen peroxide solution. Furthermore, POM was relatively more susceptible
to erosion and swelling because of the infiltration of H2O2 solution.
Calculations of the diffusion coefficient at different temperatures permit
further understanding of the chemical phenomena involved in the level of
oxidation in the course of MD simulations. Results of the simulations are
generally consistent with the previous experimental available in literature. The
simulations also provide new insights into understanding the mechanism resulting
oxidation products among the interested polymers.
PMID- 25133292
TI - Development of bifunctional chelates bearing hydroxamate arms for highly
efficient (64)Cu radiolabeling.
AB - Convenient approaches for the synthesis of DOTHA2 and NOTHA2, two cyclic
bifunctional chelates (BFCs) bearing hydroxamate arms, have been developed. These
novel BFCs coordinate (64)Cu with fast kinetics at room temperature in a wide
range of concentrations and pH. The corresponding radiochemical complexes showed
high stability, low residual activity in various tissues, and fast clearance in
normal mice. The ability to conjugate DOTHA2 to both a small peptide and a large
protein is also reported.
PMID- 25133293
TI - Preparation of biointeractive glycoprotein-conjugated hydrogels through metabolic
oligosacchalide engineering.
AB - In the current study, synthetic hydrogels containing metabolically engineered
glycoproteins of mammalian cells were prepared for the first time and selectin
mediated cell adhesion on the hydrogel was demonstrated. A culture of HL-60 cells
was supplemented with an appropriate volume of aqueous solution of N-methacryloyl
mannosamine (ManMA) to give a final concentration of 5 mM. The cells were then
incubated for 3 days to deliver methacryloyl groups to the glycoproteins of the
cells. A transparent hydrogel was formed via redox radical polymerization of
methacryloyl functionalized glycoproteins with 2-methacryloyloxyethyl
phosphorylcholine and a cross-linker. Conjugation of the glycoproteins into the
hydrogel was determined using Coomassie brilliant blue (CBB) and periodic acid
Schiff (PAS) staining. The surface density of P-selectin glycoprotein ligand-1
(PSGL-1) on the hydrogels was also detected using gold-colloid-labeled
immunoassay. Finally, selectin-mediated cell adhesion on hydrogels containing
glycoproteins was demonstrated. Selectin-mediated cell adhesion is considered an
essential step in the progression of various diseases; therefore, hydrogels
having glycoproteins could be useful in therapeutic and diagnostic applications.
PMID- 25133294
TI - Peroxides as "switches" of dialkyl H-phosphonate: two mild and metal-free methods
for preparation of 2-acylbenzothiazoles and dialkyl benzothiazol-2
ylphosphonates.
AB - Two mild and metal-free methods for the preparation of two kinds of important
benzothiazole derivatives, 2-acylbenzothiazoles and dialkyl benzothiazol-2
ylphosphonates, respectively, were developed. The dialkyl H-phosphonate
(RO)2P(O)H exists in equilibrium with its tautomer dialkyl phosphite (RO)2POH.
TBHP triggered alpha-carbon-centered phosphite radical formation, whereas DTBP
triggered phosphorus-centered phosphonate radical formation. The two types of
radicals led respectively to two different reaction processes, the direct C2
acylation of benzothiazoles and C2-phosphonation of benzothiazoles.
PMID- 25133295
TI - Discovery of a highly selective caspase-3 substrate for imaging live cells.
AB - Caspases are a family of cysteine proteases that are well-known for their roles
in apoptosis and inflammation. Recent studies provide evidence that caspases are
also integral to many additional cellular processes, such as differentiation and
proliferation. Likewise, aberrant caspase activity has been implicated in the
progression of several diseases, including neurodegenerative disorders, cancer,
cardiovascular disease, and sepsis. These observations establish the importance
of caspases to a diverse array of physiological functions and future endeavors
will undoubtedly continue to elucidate additional processes that require caspase
activity. Unfortunately, the existence of 11 functional human caspases, with
overlapping substrate specificities, confounds the ability to confidently assign
one or more isoforms to biological phenomena. Herein, we characterize a first-in
class FRET substrate that is selectively recognized by active caspase-3 over
other initiator and executioner caspases. We further apply this substrate to
specifically image caspase-3 activity in live cells undergoing apoptosis.
PMID- 25133296
TI - Dynamics of ADHD in familial contexts: perspectives from children and parents and
implications for practitioners.
AB - This article provides in-depth insights on the bidirectional dynamics between
parents and their children with attention deficit hyperactivity disorder (ADHD).
Five family units (8 parents, 5 children, N = 13) participated in this study.
Parents and their child with ADHD were interviewed individually in their homes.
Stressful moments of parent-child dynamics revolved around managing their child's
behavior and doing homework. Findings highlight the child's agency and power of
influence, and the possible recovery of negative dynamics. It is recommended that
practitioners adopt the strengths perspective in working with these families and
incorporate child's agency and bidirectional dynamics in interventions.
PMID- 25133297
TI - In the front line: the impact of specialist training for hospital physicians in
children at risk on their collaboration with social workers.
AB - Until recently, dealing with children at risk in Israeli hospitals was almost
exclusively the domain of medical social workers. Suspected cases of abuse or
neglect must be identified in real-time, during the child's short stay in the
hospital, and the decision of whether or not to report the case, and to whom (law
enforcement or welfare authorities), must be made. The recognition that effective
treatment also demands the involvement of physicians led to the development of an
intensive training program for hospital-pediatricians. The current study, based
on in-depth interviews with the doctors who participated in the program and the
social workers who work with them at 14 hospitals in Israel, examined the impact
of the training on cooperation between the two groups, seeking to determine
whether the doctors' increased familiarity with the social work profession
enhanced team-work. Phenomenological analysis of the interviews revealed several
themes, indicating greater collaboration between the doctors and social workers.
However, the participants also noted increased friction between the two groups.
Possible explanations and practical recommendations for enhancing the potential
effectiveness of such collaborations are offered. The study has implications for
designing similar training programs as well as for improving the dynamics between
the two professions.
PMID- 25133298
TI - Families with children with medical complexity and self-management of care: a
systematic review of the literature.
AB - This review analyzes the quantitative literature on children with medical
complexity (CMC). Using the Pediatric Self-Management Model, evidence is
summarized into facilitators and barriers to self-management. Current
quantitative research focuses on the caregiver burden in families with CMC. A
model for social work with families with CMC was introduced in response to these
findings. A re-envisioned model allows the child with medical complexity to be
seen as whole rather than focusing on typically deficit-based areas of medical
specialty or service provision.
PMID- 25133299
TI - Screening, testing, and reporting for drug and alcohol use on labor and delivery:
a survey of Maryland birthing hospitals.
AB - Recent amendments to the Child Abuse Prevention and Treatment Act tie the receipt
of federal block grants to mandatory reporting of substance-exposed newborns. To
determine rates of screening, testing, and reporting of drug and alcohol use at
the time of delivery, we administered a telephone survey of nursing managers and
perinatal social workers at Maryland birthing hospitals. Of the 34 hospitals, 31
responded (response rate 91%). Although 97% of hospitals reported universal
screening, only 6% used a validated instrument. Testing was reported by 94% with
45% reporting universal maternal testing and 7% universal newborn testing. Only
32% reported obtaining maternal consent prior to testing. There is significant
heterogeneity in screening and testing for substance use in birthing hospitals.
Given federal reporting mandates, state-level practices need to be standardized.
PMID- 25133300
TI - Caregivers' experience in patients with chronic diseases.
AB - The aim of this study was to describe the characteristics of caregivers of
patients with chronic diseases, assess their perceived burden, and investigate
factors influencing this burden. Seventy-three patient-attendants (43 men and 30
women) participated in the pilot-research conducted by two clinics. Of them, 68%
attended patients with a malignant disease and 32% attended patients in the end
stage of renal disease. Based on questionnaire data, the influence of the social
support was studied, in particular that of family members or through state
programmers. Family members are the primary caregivers (spouses 51%, children
29%, and others 20%). Psychological support is the main important help that they
need and there are a small number of caregivers who have access to a network of
medical and social support. It is found that the family still remains the main
supporting mechanism for attendants and patients in our population.
PMID- 25133301
TI - Long-term care insurance in China: public or private?
AB - China faces an overwhelming and urgent need for long-term care (LTC). We explored
long-term care insurance (LTCI) plans in China and the factors associated with
each plan's contribution rate. A cross-sectional survey of 814 residents (18-59
years) was conducted to assess the expectations of elderly care, public and
private LTCI features. Public LTCI may be more popular whether in terms of
participation or contribution. The factors associated with public LTCI
contribution rate were healthcare costs, household income, and number of
daughters; for private LTCI, the factors were the proportion of living
expenditures, worry about future care problems, and healthcare costs.
Policymakers should develop public LTCI as a solid foundation and improve private
LTCI as a substitute to meet the urgent LTC needs in China.
PMID- 25133302
TI - Nanocrystal grain growth and device architectures for high-efficiency CdTe ink
based photovoltaics.
AB - We study the use of cadmium telluride (CdTe) nanocrystal colloids as a solution
processable "ink" for large-grain CdTe absorber layers in solar cells. The
resulting grain structure and solar cell performance depend on the initial
nanocrystal size, shape, and crystal structure. We find that inks of
predominantly wurtzite tetrapod-shaped nanocrystals with arms ~5.6 nm in diameter
exhibit better device performance compared to inks composed of smaller tetrapods,
irregular faceted nanocrystals, or spherical zincblende nanocrystals despite the
fact that the final sintered film has a zincblende crystal structure. Five
different working device architectures were investigated. The indium tin oxide
(ITO)/CdTe/zinc oxide structure leads to our best performing device architecture
(with efficiency >11%) compared to others including two structures with a cadmium
sulfide (CdS) n-type layer typically used in high efficiency sublimation-grown
CdTe solar cells. Moreover, devices without CdS have improved response at short
wavelengths.
PMID- 25133303
TI - A longitudinal study of an intervention to improve road safety climate: climate
as an organizational boundary spanner.
AB - This study presents and tests an intervention to enhance organizational climate
and expands existing conceptualization of organizational climate to include its
influence on employee behaviors outside the organization's physical boundaries.
In addition, by integrating the literatures of climate and work-family interface,
the study explored climate spillover and crossover from work to the home domain.
Focusing on an applied practical problem within organizations, we investigated
the example of road safety climate and employees' and their families' driving,
using a longitudinal study design of road safety intervention versus control
groups. Results demonstrated that the intervention increased road safety climate
and decreased the number of traffic violation tickets and that road safety
climate mediated the relationship between the intervention and the number of
traffic violation tickets. Road safety climate spilled over to the family domain
but did not cross over to influence family members' driving.
PMID- 25133304
TI - A meta-analysis of the relationship between general mental ability and nontask
performance.
AB - Although one of the most well-established research findings in industrial
organizational psychology is that general mental ability (GMA) is a strong and
generalizable predictor of job performance, this meta-analytically derived
conclusion is based largely on measures of task or overall performance. The
primary purpose of this study is to address a void in the research literature by
conducting a meta-analysis to determine the direction and magnitude of the
correlation of GMA with 2 dimensions of nontask performance: counterproductive
work behaviors (CWB) and organizational citizenship behaviors (OCB). Overall, the
results show that the true-score correlation between GMA and CWB is essentially 0
(-.02, k = 35), although rating source of CWB moderates this relationship. The
true-score correlation between GMA and OCB is positive but modest in magnitude
(.23, k = 43). The 2nd purpose of this study is to conduct meta-analytic relative
weight analyses to determine the relative importance of GMA and the five-factor
model (FFM) of personality traits in predicting nontask and task performance
criteria. Results indicate that, collectively, the FFM traits are substantially
more important for CWB than GMA, that the FFM traits are roughly equal in
importance to GMA for OCB, and that GMA is substantially more important for task
and overall job performance than the FFM traits. Implications of these findings
for the development of optimal selection systems and the development of
comprehensive theories of job performance are discussed along with study
limitation and future research directions. (PsycINFO Database Record (c) 2014
APA, all rights reserved).
PMID- 25133305
TI - DUI offenders' experience with an ignition interlock program: comparing those who
have and have not adapted from their primary drinking location.
AB - OBJECTIVE: The purpose of this study was to compare driving under the influence
(DUI) offenders on an alcohol ignition interlock program who had or had not
changed their primary drinking context from a bar/restaurant where they might be
required to drive after drinking before the interlock was installed to drinking
at home where driving would not be likely to be required following interlock
installation. METHODS: A total of 171 DUI offenders who were on an ignition
interlock program completed a web-based survey. All of these offenders reported
that they drank primarily in a bar/restaurant before the interlock was installed.
These offenders were classified into 2 groups: adapters who said they currently
drink at home and nonadapters who said they still drink in a bar/restaurant.
Measures were made of their reported drinking, driving patterns, perceptions of
the likely outcomes of being on the interlock, perceived effectiveness of various
prevention strategies, and demographic characteristics. Chi-square and t-test
analyses were used to compare these 2 groups. RESULTS: Adapters and nonadapters
did not differ with regard to any of the demographic characteristics, whether
they were a first-time DUI offender, the length of time in the interlock program,
number of lockouts (being blocked from starting their cars) they had experienced,
miles driven per week, or current driving patterns since being on the interlock
program. Adapters were more likely to report changing their drinking plans and
habits. Currently they reported fewer drinks per occasion than nonadapters. They
were more likely to report reducing the amount they drink, solo drinking or only
drinking with a spouse/significant other, and changing their drinking plans and
habits. They were also more likely to say that the interlock reminded them to
limit their drinking after it is removed and that it might have longer term
benefits in preventing future DUIs. They were also more receptive to
interventions that might help them separate their drinking from their driving.
CONCLUSIONS: Interlock clients who report that they have altered their drinking
context and a willingness to receive programs that help them separate their
drinking from their driving may be more receptive to and benefit from ignition
interlock programs.
PMID- 25133306
TI - Is cerebrospinal fluid obtained for diagnostic purpose a good material for
biomarker studies in amyotrophic lateral sclerosis?
AB - The cerebrospinal fluid (CSF) used for identification of molecular biomarkers in
amyotrophic lateral sclerosis (ALS) is mainly obtained from lumbar puncture (LP)
performed to exclude other causes of motor neuron damage. AIM: The aim of the
study was to analyze whether CSF of ALS patients obtained for diagnostic purposes
is suitable for biomarker studies in the entire ALS population. MATERIAL AND
METHODS: We analyzed the medical data, LP frequency and CSF parameters in 568 ALS
patients. RESULTS: LP was performed in 34% of cases. Patients who underwent LP
were significantly younger and more frequently presented limb onset ALS, there
were no differences in the clinical phenotypes. CONCLUSION: CSF obtained for
diagnostic purposes can be used for biomarkers studies in ALS.
PMID- 25133309
TI - 3D artificial bones for bone repair prepared by computed tomography-guided fused
deposition modeling for bone repair.
AB - The medical community has expressed significant interest in the development of
new types of artificial bones that mimic natural bones. In this study, computed
tomography (CT)-guided fused deposition modeling (FDM) was employed to fabricate
polycaprolactone (PCL)/hydroxyapatite (HA) and PCL 3D artificial bones to mimic
natural goat femurs. The in vitro mechanical properties, in vitro cell
biocompatibility, and in vivo performance of the artificial bones in a long load
bearing goat femur bone segmental defect model were studied. All of the results
indicate that CT-guided FDM is a simple, convenient, relatively low-cost method
that is suitable for fabricating natural bonelike artificial bones. Moreover,
PCL/HA 3D artificial bones prepared by CT-guided FDM have more close mechanics to
natural bone, good in vitro cell biocompatibility, biodegradation ability, and
appropriate in vivo new bone formation ability. Therefore, PCL/HA 3D artificial
bones could be potentially be of use in the treatment of patients with clinical
bone defects.
PMID- 25133308
TI - Early-lethal Costello syndrome due to rare HRAS Tandem Base substitution
(c.35_36GC>AA; p.G12E)-associated pulmonary vascular disease.
AB - Costello syndrome is a rare, autosomal-dominant syndrome caused by activating
missense mutations in the Harvey rat sarcoma viral oncogene homolog (HRAS), most
often p.G12S. Several rare mutations have consistently been associated with a
more severe phenotype that is often lethal in infancy. Cause of death is most
often respiratory failure, with hypertrophic cardiomyopathy playing a significant
role in morbidity. Impaired fibroblast elastogenesis is thought to contribute to
the Costello phenotype, but reports of histologic evidence of disordered
elastogenesis at autopsy are limited. We report a patient with Costello syndrome
due to a rare tandem base substitution (c.35_36GC>AA) resulting in the p.G12E
missense change. The proband died at the age of 3 months from respiratory
failure, with minimal evidence of cardiomyopathy. The autopsy disclosed pulmonary
vascular dysplasia affecting small arteries and veins associated with abnormal
elastin distribution in tortuous dilated arteries and veins, with nonuniform wall
thickness and semiobstructive lesions at artery branch points typical of early
pulmonary hypertensive vascular disease. Elastic fibers in the dermis were
abnormally short and fragmented. This case suggests that disordered elastogenesis
in the pulmonary vasculature and undiagnosed (or underdiagnosed) pulmonary
hypertension may contribute to morbidity in patients with Costello syndrome.
PMID- 25133311
TI - Emergence of DNA-encapsulating liposomes from a DNA-lipid blend film.
AB - Spontaneous generation of DNA-enclosing liposomes from a DNA-lipid blend film is
investigated. The special properties of the lipid vesicles, namely, micrometer
size, unilamellarity, and dense polymer encapsulation acquired by the dehydration
rehydration process, are physicochemically revealed. We found that the formation
of giant unilamellar vesicles encapsulating DNAs are governed by micropatterns of
the films, such as dots and network patterns. From the results, we proposed a
plausible physical mechanism for the dehydration-rehydration process, making it
possible to optimize the encapsulation of any agent.
PMID- 25133310
TI - NanoScript: a nanoparticle-based artificial transcription factor for effective
gene regulation.
AB - Transcription factor (TF) proteins are master regulators of transcriptional
activity and gene expression. TF-based gene regulation is a promising approach
for many biological applications; however, several limitations hinder the full
potential of TFs. Herein, we developed an artificial, nanoparticle-based
transcription factor, termed NanoScript, which is designed to mimic the structure
and function of TFs. NanoScript was constructed by tethering functional peptides
and small molecules called synthetic transcription factors, which mimic the
individual TF domains, onto gold nanoparticles. We demonstrate that NanoScript
localizes within the nucleus and initiates transcription of a reporter plasmid by
over 15-fold. Moreover, NanoScript can effectively transcribe targeted genes on
endogenous DNA in a nonviral manner. Because NanoScript is a functional replica
of TF proteins and a tunable gene-regulating platform, it has great potential for
various stem cell applications.
PMID- 25133312
TI - Dehalogenation of aromatics by nucleophilic aromatic substitution.
AB - Nucleophilic aromatic substitution has been implicated as a mechanism for both
the biotic and abiotic hydrodehalogenation of aromatics. Two mechanisms for the
aqueous dehalogenation of aromatics involving nucleophilic aromatic substitution
with hydride as a nucleophile are investigated using a validated density
functional and continuum solvation protocol. For chlorinated and brominated
aromatics, nucleophilic addition ortho to carbon-halogen bonds via an anionic
intermediate is predicted to be the preferred mechanism in the majority of cases,
while concerted substitution is predicted to be preferred for most fluorinated
aromatics. Nucleophilic aromatic substitution reactions with the hydroxide and
hydrosulfide anions as nucleophiles are also investigated and compared.
PMID- 25133307
TI - Role of protein-protein interactions in cytochrome P450-mediated drug metabolism
and toxicity.
AB - Through their unique oxidative chemistry, cytochrome P450 monooxygenases (CYPs)
catalyze the elimination of most drugs and toxins from the human body. Protein
protein interactions play a critical role in this process. Historically, the
study of CYP-protein interactions has focused on their electron transfer partners
and allosteric mediators, cytochrome P450 reductase and cytochrome b5. However,
CYPs can bind other proteins that also affect CYP function. Some examples include
the progesterone receptor membrane component 1, damage resistance protein 1,
human and bovine serum albumin, and intestinal fatty acid binding protein, in
addition to other CYP isoforms. Furthermore, disruption of these interactions can
lead to altered paths of metabolism and the production of toxic metabolites. In
this review, we summarize the available evidence for CYP protein-protein
interactions from the literature and offer a discussion of the potential impact
of future studies aimed at characterizing noncanonical protein-protein
interactions with CYP enzymes.
PMID- 25133313
TI - Ligularia fischeri extract protects against oxidative-stress-induced
neurotoxicity in mice and PC12 cells.
AB - Alzheimer's disease (AD) is pathologically characterized by the presence of
amyloid plaques in brain and the overproduction of amyloid beta (Abeta), leading
to learning and memory impairment and intense oxidative stress. In this study,
the protective effect of Ligularia fischeri extract was investigated using PC12
cells. L. fischeri extract attenuated hydrogen-peroxide-induced DNA fragmentation
in cells. In vivo behavioral tests were performed to examine the effects of the
extract on amyloid-beta peptide1-42-induced impairment of learning and memory in
mice. A diet containing the extract increased alternation behaviors in the Y-maze
test and step-through latency of passive avoidance task. Moreover, we found that
consumption of the extract decreased lipid peroxidation in a biochemical study of
brain tissue in mice. High-performance liquid chromatography was used to identify
the active compounds in the extract. These results suggest that L. fischeri
extract could be protective against Abeta-induced neurotoxicity, possibly due to
the antioxidative capacity of its constituent, 3-O-caffeoylquinic acid.
PMID- 25133315
TI - Effects of urban sprawl and vehicle miles traveled on traffic fatalities.
AB - OBJECTIVE: Previous research suggests that urban sprawl increases auto-dependency
and that excessive auto use increases the risk of traffic fatalities. This
indirect effect of urban sprawl on traffic fatalities is compared to non-vehicle
miles traveled (VMT)-related direct effect of sprawl on fatalities. METHODS: We
conducted a path analysis to examine the causal linkages among urban sprawl, VMT,
traffic fatalities, income, and fuel cost. The path diagram includes 2 major
linkages: the direct relationship between urban sprawl and traffic fatalities and
the indirect effect on fatalities through increased VMT in sprawling urban areas.
To measure the relative strength of these causal linkages, path coefficients are
estimated using data collected nationally from 147 urbanized areas in the United
States. RESULTS: Through both direct and indirect paths, urban sprawl is
associated with greater numbers of traffic fatalities, but the direct effect of
sprawl on fatalities is more influential than the indirect effect. CONCLUSIONS:
Enhancing traffic safety can be achieved by impeding urban sprawl and encouraging
compact development. On the other hand, policy tools reducing VMT may be less
effective than anticipated for traffic safety.
PMID- 25133316
TI - Synthesis and arm dissociation in molecular stars with a spoked wheel core and
bottlebrush arms.
AB - Unique star-like polymeric architectures composed of bottlebrush arms and a
molecular spoked wheel (MSW) core were prepared by atom transfer radical
polymerization (ATRP). A hexahydroxy-functionalized MSW (MSW(6-OH)) was
synthesized and converted into a six-fold ATRP initiator (MSW(6-Br)). Linear
chain arms were grafted from MSW(6-Br) and subsequently functionalized with ATRP
moieties to form six-arm macroinitiators. Grafting of side chains from the
macroinitiators yielded four different star-shaped bottlebrushes with varying
lengths of arms and side chains, i.e., (450-g-20)6, (450-g-40)6, (300-g-60)6, and
(300-g-150)6. Gel permeation chromatography analysis and molecular imaging by
atomic force microscopy confirmed the formation of well-defined macromolecules
with narrow molecular weight distributions. Upon adsorption to an aqueous
substrate, the bottlebrush arms underwent prompt dissociation from the MSW core,
followed by scission of covalent bonds in the bottlebrush backbones. The
preferential cleavage of the arms is attributed to strong steric repulsion
between bottlebrushes at the MSW branching center. Star-shaped macroinitiators
may undergo aggregation which can be prevented by sonication.
PMID- 25133314
TI - SIN3 is critical for stress resistance and modulates adult lifespan.
AB - Coordinate control of gene activity is critical for fitness and longevity of an
organism. The SIN3 histone deacetylase (HDAC) complex functions as a
transcriptional repressor of many genes. SIN3-regulated genes include those that
encode proteins affecting multiple aspects of mitochondrial function, such as
energy production and stress responsiveness, important for health maintenance.
Here we used Drosophila melanogaster as a model organism to examine the role of
SIN3 in the regulation of fitness and longevity. Adult flies with RNA
interference (RNAi) induced knockdown expression of Sin3A have reduced climbing
ability; an activity that likely requires fully functional mitochondria.
Additionally, compared to wild type, adult Sin3A knockdown flies were more
sensitive to oxidative stress. Interestingly, media supplementation with the
antioxidant glutathione largely restored fly tolerance to oxidative stress.
Although Sin3A knockdown flies exhibited decreased longevity compared to wild
type, no significant changes in expression of many well-categorized aging genes
were observed. We found, however, that Sin3A knockdown corresponded to a
significant reduction in expression of genes encoding proteins involved in the de
novo synthesis of glutathione. Taken together, the data support a model whereby
SIN3 regulates a gene expression program required for proper mitochondrial
function and effective stress response during adulthood.
PMID- 25133318
TI - Interhemispheric collaboration during digit and dot number-matching in younger
and older adults.
AB - Digit and dot number-matching stimuli were used to replicate findings reported
for younger adults by Patel and Hellige (2007) and to explore whether performance
would differ for younger versus older participants. Participants were to make
numerical matches of digits only, dots only, and digits and dots mixed conditions
to determine whether reaction time (RT), percentage error, and efficiency scores
that combine latency and accuracy for match trials were better on within- versus
across-hemisphere trials. Sixty-six younger and 42 older participants were
screened with the Mini-Mental State Examination (MMSE) and the Geriatric
Depression Scale. They performed the three experimental conditions and were
assessed with Digit Span Forward and Backward subscales from the Wechsler Adult
Intelligence Scale-III. Results for younger adults demonstrated a within
hemisphere advantage for the Digits and Mixed conditions and an across-hemisphere
advantage for the Dots condition, consistent with previous literature. Older
participants showed a stronger within-hemisphere advantage for the Digits
condition compared with younger participants and no advantage for within- or
across-hemisphere processing for the Mixed condition when RT was considered, but
they performed similarly to younger adults when efficiency scores were used and
showed a relative across-hemisphere advantage for the Dots condition. Although RT
suggests age-related differences in how information is distributed across the
hemispheres of the brain, more comprehensive efficiency scores indicate that
younger and older adults appear to use similar strategies in the coordination of
interhemispheric transfer of information. MMSE scores regardless of age were
related to type of task but not to across- versus within-hemisphere performance.
PMID- 25133317
TI - The posteromedial region of the default mode network shows attenuated task
induced deactivation in psychopathic prisoners.
AB - OBJECTIVE: Psychopathy is a personality disorder with symptoms that include lack
of empathy or remorse, antisocial behavior, and excessive self-focus. Previous
neuroimaging studies have linked psychopathy to dysfunction in the default mode
network (DMN), a brain network that deactivates during externally focused tasks
and is more engaged during self-referential processing. Specifically, the DMN has
been found to remain relatively active in individuals with psychopathic
tendencies during externally focused tasks, suggesting a failure to properly
deactivate. However, the exact extent and nature of task-induced DMN dysfunction
is poorly understood, including (a) the degree to which specific DMN subregions
are affected in criminal psychopaths, and (b) how activity in these subregions
relates to affective/interpersonal and antisocial/lifestyle traits of
psychopathy. METHOD: We performed a group independent component analysis to
assess DMN activation during a Go/NoGo task in a group of 22 high-psychopathy and
22 low-psychopathy prisoners. The identified group-level DMN was parcellated into
6 subregions, and group differences in task-induced activity were examined.
RESULTS: In general, DMN subregions failed to deactivate beneath baseline in the
high-psychopathy group. A group comparison with the low-psychopathy group
localized this attenuated task-induced deactivation to the posteromedial cortical
(mPC) region of the DMN. Moreover, multiple regression analyses revealed that
activity in the mPC was associated with affective/interpersonal traits of
psychopathy. CONCLUSION: These findings suggest that attenuated deactivation of
the mPC subregion of the DMN is intrinsic to psychopathy, and is a pattern that
may be more associated with affective psychopathic traits, including lack of
concern for others.
PMID- 25133320
TI - Parenthood and Physical Activity in Young Adults: A Qualitative Study.
AB - BACKGROUND: New parents have to adjust to less sleep, less free time, and more
responsibility as a result of having a child. The purpose of this study was to
examine how having a child impacts the physical activity (PA) beliefs and
behaviors of new parents over a 2- to 3-year time period. METHODS: Participants
included 49 men and women (31% men, 96% white) who did not have a child at
baseline (26.3 +/- 1.1 years old) but did have a child at the time of follow-up
(28.9 +/- 1.7 years old). The child's mean age at follow-up was 12 +/- 7 months
old. PA was measured via questionnaire at baseline and again at follow-up.
Interviews regarding PA occurred at follow-up. RESULTS: PA significantly
decreased in parents across the time period (P < .001), and parents attributed
this decrease to having a child and being pregnant. Parents mentioned they lack
time, energy, and motivation for PA as a result of caring for a new child.
Parents who maintained their activity level stated they prioritized PA and chose
activities they enjoyed. CONCLUSIONS: These results show that although activity
levels decrease in individuals who have a child, PA in new parents may be a
function of priority, intensity, and enjoyment.
PMID- 25133321
TI - Synthesis, characterization, and swelling behaviors of salt-sensitive maize bran
poly(acrylic acid) superabsorbent hydrogel.
AB - A novel composite hydrogel was prepared via UV irradiation copolymerization of
acrylic acid and maize bran (MB) in the presence of composite initiator (2,2
dimethoxy-2-phenylacetophenone and ammonium persulfate) and cross-linker (N,N'
methylenebis(acrylamide)). Under the optimized conditions, maize bran
poly(acrylic acid) was obtained (2507 g g(-1) in distilled water and 658 g g(-1)
in 0.9 wt % NaCl solution). Effects of granularity, salt concentration, and
various cations and anions on water absorbency were investigated. It was found
that swelling was extremely sensitive to the ionic strength and cation and anion
type. Swelling kinetics and water diffusion mechanism in distilled water were
also discussed. Moreover, the product showed excellent water retention capability
under the condition of high temperature or high pressure. The salt sensitivity,
good water absorbency, and excellent water retention capability of the hydrogels
give this intelligentized polymer wide potential applications.
PMID- 25133319
TI - Anosognosia for hemiplegia: The contributory role of right inferior frontal
gyrus.
AB - OBJECTIVE: Awareness of motor functioning is most likely a complex process that
requires integration of sensory-motor feedback to constantly update the system on
the functioning of the limb during motor behavior. Using lesion mapping
procedures and behavioral measures, the current study aimed to evaluate neural
correlates of anosognosia for hemiplegia (AHP) in the acute stage (first 48 hr)
of right hemisphere stroke. METHOD: Thirty-five individuals with right hemisphere
stroke who presented to an urban medical center within 24 hr of symptom onset
were included in the study. All 35 individuals had hemiplegia, and 8 of these
individuals exhibited AHP. RESULTS: Fisher's exact test statistical map of lesion
deficit association (range is between-log(p) 4 to 11) found maximal value of 10.9
located in pars orbitalis (Brodmann's Area 47; BA). In this selected location, 6
out of 8 patients with AHP had tissue abnormality, whereas none of the unaffected
subjects had tissue abnormality in BA 47. Right BA 44/45 was also found to be
lesioned more frequently in individuals with AHP (75%) than without AHP (11%).
CONCLUSIONS: The current study findings provide preliminary support for unique
involvement of the right inferior frontal gyrus (IFG), pars orbitalis (BA 47) in
AHP. The current data suggest that frontal operculum may play a key role in
awareness of limb functioning.
PMID- 25133323
TI - Detection of low-concentration contaminants in solution by exploiting chemical
derivatization in surface-enhanced Raman spectroscopy.
AB - A simple derivatization methodology is shown to extend the application of surface
enhanced Raman spectroscopy (SERS) to the detection of trace concentration of
contaminants in liquid form. Normally in SERS the target analyte species is
already present in the molecular form in which it is to be detected and is
extracted from solution to occupy sites of enhanced electromagnetic field on the
substrate by means of chemisorption or drop-casting and subsequent evaporation of
the solvent. However, these methods are very ineffective for the detection of low
concentrations of contaminant in liquid form because the target (ionic) species
(a) exhibits extremely low occupancy of enhancing surface sites in the bulk
liquid environment and (b) coevaporates with the solvent. In this study, the
target analyte species (acid) is detected via its solid derivative (salt)
offering very significant enhancement of the SERS signal because of preferential
deposition of the salt at the enhancing surface but without loss of chemical
discrimination. The detection of nitric acid and sulfuric acid is demonstrated
down to 100 ppb via reaction with ammonium hydroxide to produce the corresponding
ammonium salt. This yields an improvement of ~4 orders of magnitude in the low
concentration detection limit compared with liquid phase detection.
PMID- 25133322
TI - Electroporation-delivered fluorescent protein biosensors for probing molecular
activities in cells without genetic encoding.
AB - Fluorescent protein biosensors are typically implemented via genetic encoding
which makes the examination of scarce cell samples impractical. By directly
delivering the protein form of the biosensor into cells using electroporation, we
detected intracellular molecular activity with the sample size down to ~100 cells
with high spatiotemporal resolution.
PMID- 25133324
TI - Health threat associated with Caucasian giant hogweeds: awareness among doctors
and general public in Poland.
AB - CONTEXT: The Caucasian giant hogweeds (Heracleum sosnowskyi and H.
mantegazzianum) are aggressive invaders successfully spreading across different
parts of Europe. Their sap containing linear furanocoumarins can lead to a
persisting cutaneous dermatitis and massive skin necrosis. OBJECTIVE: We aimed to
assess the awareness of the giant hogweeds' threat among physicians and general
public in Poland. METHODS: The level of awareness was assessed using a short
questionnaire given to different groups of physicians: dermatologists (DMs),
general practitioners (GPs) and occupational practitioners (OPs). An independent
questionnaire was also addressed to the general public. RESULTS: Among the
surveyed physician groups, DMs were the best informed, while OPs were the worst
informed on health threats associated with the giant hogweeds and treatment
methods. Most frequently, application of topical corticosteroids was indicated as
a successful method of treatment following the exposure to hogweeds. In the
general public, awareness was relatively low with only 57.7% of the surveyed
having ever heard about these plants. TV, press and Internet were among the most
frequent sources of information in this regard. CONCLUSIONS: Public and medical
attention needs to be raised as to the threats associated with giant hogweeds,
particularly in countries that are highly infested with these plants.
PMID- 25133325
TI - Infrared and Raman spectra, theoretical calculations, conformations, and two
dimensional potential energy surface of 2-cyclopenten-1-one ethylene ketal.
AB - The infrared and Raman spectra of the bicyclic spiro molecule 2-cyclopenten-1-one
ethylene ketal (CEK) have been recorded. Density functional theory (DFT)
calculations were used to compute the theoretical spectra, and these agree well
with the experimental spectra. The structures and conformational energies for the
two pairs of conformational minima, which can be defined in terms of ring-bending
(x) and ring-twisting (tau) vibrational coordinates, have also been calculated.
Utilizing the results from ab initio MP2/cc-PVTZ computations, a two-dimensional
potential energy surface (PES) was calculated. The energy levels and wave
functions for this PES were then calculated, and the characteristics of these
were analyzed. At lower energies, all of the quantum states are doubly degenerate
and correspond to either the lower-energy conformation L or to conformation H,
which is 154 cm(-1) higher in energy. At energies above the barrier to
interconversion of 264 cm(-1), the wave functions show that the quantum levels
have significant probabilities for both conformations.
PMID- 25133326
TI - Natural course vs interventions to clear common bile duct stones: data from the
Swedish Registry for Gallstone Surgery and Endoscopic Retrograde
Cholangiopancreatography (GallRiks).
AB - IMPORTANCE: The optimal strategy for common bile duct stones (CBDSs) encountered
during cholecystectomy is yet to be determined. OBJECTIVE: To evaluate the
outcomes after various interventional techniques to clear the bile ducts and the
natural course of CBDSs found during intraoperative cholangiography. DESIGN,
SETTING, AND PARTICIPANTS: In a large retrospective cohort analysis, we analyzed
data from the Swedish Registry for Gallstone Surgery and Endoscopic Retrograde
Cholangiopancreatography (GallRiks). We included all patients with CBDSs found on
intraoperative cholangiography during cholecystectomy from May 1, 2005, through
December 31, 2009. EXPOSURES: Presence of CBDSs on intraoperative
cholangiography. MAIN OUTCOMES AND MEASURES: Relation between strategies for
handling CBDSs in terms of complication rates and/or incomplete clearance with
need of intervention (ie, unfavorable outcomes). RESULTS: In 38,864
cholecystectomies, CBDSs were found in 3969 patients, of whom 3828 underwent
analysis. Earlier or ongoing symptoms were more common with increasing stone size
(P < .001). In total, postoperative unfavorable outcomes were found in 14.9% but
less frequently for patients with smaller stones (P < .01). Among patients in
whom no intraoperative measures were taken (representing natural course), the
risk for unfavorable outcomes was 25.3%. This risk was significantly lower in
patients in whom any measure was taken to clear the ducts (12.7%; odds ratio,
0.44 [95% CI, 0.35-0.55]). The same was found when small (<4 mm) and medium (4-8
mm) stones were analyzed separately (odds ratio, 0.52 [95% CI, 0.34-0.79] and
0.24 [95% CI, 0.17-0.32], respectively). CONCLUSIONS AND RELEVANCE: The high
rates of unfavorable outcomes associated with taking no measures when CBDSs are
found during cholecystectomy suggest that the natural course might not be as
favorable as earlier suggested. This finding implies that, in general, efforts
should be made to clear the bile ducts.
PMID- 25133340
TI - Now available: wound care-related quality measures.
PMID- 25133328
TI - Subcutaneous veltuzumab, a humanized anti-CD20 antibody, in the treatment of
refractory pemphigus vulgaris.
AB - IMPORTANCE B-cell depletion with the anti-CD20 antibody rituximab is highly
effective for pemphigus vulgaris (PV) treatment. However,most patients experience
relapse, and intravenous rituximab infusions are expensive. Therefore, cost
effective anti-CD20 therapies are desirable.OBSERVATIONS A compassionate-use
investigational new drug protocol was approved to administer veltuzumab, a second
generation humanized anti-CD20 antibody, to a patient with refractory PV.
Veltuzumab was administered as two 320-mg (188mg/m2) subcutaneous doses 2 weeks
apart, resulting in complete remission of disease off therapy. The disease
relapsed 2 years after treatment. A second cycle of subcutaneous veltuzumab,
using the same dosage regimen, again induced complete remission off therapy,
which remained at9 months. No serious adverse events occurred during 35 months of
follow-up. Serum veltuzumab levels were 22 and 29 MUg/mL 2 weeks after the first
dose of each cycle, and the drug remained detectable in the serum for longer than
3 months. Relapse and response to veltuzumab generally correlated with desmoglein
3 enzyme-linked immunosorbent assay index values. Shortly after a relapse that
occurred after a long-term remission, the patient demonstrated an elevated naive
(CD19+CD27-) to memory (CD19+CD27+) B-cell ratio of 19.5 and transitional
(CD19+CD24+CD38+) B-cell frequency of 12.5%.CONCLUSIONS AND RELEVANCE
Subcutaneous veltuzumab may be a safe, effective, and more economical alternative
to intravenous rituximab for PV therapy. Clinical trials of subcutaneous
veltuzumab for PV are warranted.
PMID- 25133341
TI - Wounds in patients with HIV.
AB - Highly active antiretroviral therapy has dramatically reduced morbidity and
mortality among patients who are HIV-positive. A retrospective review of the
authors' data separated subjects into cohorts based on HIV status and matched
them for age and gender. The authors' data reveal a higher fraction of venous
ulcers compared with a lower fraction of pressure ulcers in the seropositive
population.
PMID- 25133327
TI - Association between occupational exposure and lung function, respiratory
symptoms, and high-resolution computed tomography imaging in COPDGene.
AB - RATIONALE: Although occupational exposure to dust and fumes is considered a risk
factor for chronic obstructive pulmonary disease, this determination has been
limited by reliance on spirometry alone to assess disease severity in
predominantly male populations. OBJECTIVES: To determine the effect of
occupational exposure on lung function, respiratory symptoms, and findings of
emphysema and airway wall thickness measured using quantitative computed
tomography in men and women. METHODS: COPDGene is a multicenter study of current
and former smokers that underwent standardized volumetric chest computed
tomography scans to assess airways, % emphysema, and % gas trapping. Spirometry
and a respiratory questionnaire including occupational history were also analyzed
in 9,614 subjects (4,496 women). Logistic regression and analysis of covariance
was used to assess associations with exposure. MEASUREMENTS AND MAIN RESULTS:
Occupational exposure to both dust and fumes was reported by 47.9% of men and
20.1% of women. Adjusting for age, race, body mass index, education, and current
and lifetime smoking, the odds ratios for persons with dust and fume exposures
for chronic cough, chronic phlegm, persistent wheeze, and Global Initiative for
Chronic Obstructive Lung Disease stages 2 and higher chronic obstructive
pulmonary disease were significantly elevated and similar for men (1.83, 1.84,
2.0, 1.61, respectively) and women (1.65, 1.82, 1.98, 1.90, respectively). The %
predicted FEV1 was similarly lower in those with exposure in men (70.7 +/- 0.8
vs. 76.0 +/- 0.9; P < 0.001) and women (70.5 +/- 0.8 vs. 77.2 +/- 0.8; P <
0.001). Percent emphysema and gas trapping was greater in those exposed to dust
and fumes in men and women. In men, but not in women, persons with exposure had a
greater mean square root wall area of 10-mm internal perimeter airways.
CONCLUSIONS: Occupational exposure to dust and fumes in men and women is
similarly associated with airflow obstruction, respiratory symptoms, more
emphysema, and gas trapping in men and women.
PMID- 25133342
TI - Excision, skin grafting, corticosteroids, adjuvant radiotherapy, pressure
therapy, and emancipation: the ESCAPE model for successful taming of giant
auricular keloids.
AB - The authors treated 24 giant auricular keloids (mean size, 11 cm) from January
2008 to July 2012 using a novel protocol consisting of complete excision, skin
grafting, a 1-time intraoperative injection of triamcinolone, immediate
radiotherapy, and sustained pressure therapy. At 1 year, the success rate was
87.5%.
PMID- 25133343
TI - The Pieper-Zulkowski pressure ulcer knowledge test.
AB - OBJECTIVE: To describe the development and initial testing of the Pieper
Zulkowski Pressure Ulcer Knowledge Test (PZ-PUKT). DESIGN: Cross-sectional,
instrument testing. SETTING: Hospital association pressure ulcer educational
program conference. METHODS: Pressure ulcer research and guidelines from the last
5 years were examined for test item content. The initial PZ-PUKT had 115 items;
response options were "true," "false," and "don't know." Registered nurses (N =
108) were randomly divided into 2 groups to take either the 60 prevention/risk
and staging items or the 55 wound description items. Analyses of these responses
resulted in 72 items, which were administered in total to a second cohort of 98
nurses for reliability. RESULTS: Cronbach's alpha was .80 for the 72-item PZ
PUKT. Cronbach's alpha values for the subscales were as follows: staging, .67;
wound description, .64; and prevention/risk, .56. The mean correct scores were as
follows: total, 80%; prevention, 77%; staging, 86%; and wound description, 77%.
Nurses with wound care certification scored significantly higher on the PZ-PUKT
than did nurses with other clinical certifications or with nurses who lacked
certification. CONCLUSIONS: The PZ-PUKT has updated content about pressure ulcer
prevention/risk, staging, and wound description. Reliability values are highest
for the total test. Further use of the instrument in diverse settings will add to
reliability testing and may provide direction for determination of a passing
cutoff score.
PMID- 25133344
TI - Arterial disease ulcers, part 1: clinical diagnosis and investigation.
AB - Arterial disease (peripheral vascular disease) is the result of narrowing of the
blood vessel lumen. The classic clinical signs need to be recognized early before
progression to arterial predominant disease and limb ischemia. Arterial ulcers or
tissue breakdown can result from trauma, infection, or other etiologies with
diabetes, smoking, increasing age, and hypertension the most important risk
factors. Diagnostic testing starts with a palpable pulse with special
investigation including handheld Doppler for ankle brachial pressure index
ratios, segmental duplex leg Doppler waveforms, and more specialized procedures,
including transcutaneous oxygen saturation.
PMID- 25133346
TI - Meaningful use audit checklist.
PMID- 25133347
TI - Phytoextraction and dissipation of lindane by Spinacia oleracea L.
AB - Remediation and management of organochlorine pesticide (OCPs) contaminated soil
is becoming a global priority as they are listed in the Stockholm list of
persistent organic pollutants (POPs) for global elimination. Lindane is a OCPs
candidate recently included in the Stockholm list. However, India has an
exemption to produce lindane for malaria control. Because of its widespread use
during the last few decades, lindane contaminated soils are found in almost all
parts of India. Since phytoremediation is widely acknowledged as an innovative
strategy for the clean-up of contaminated soils; the present study was aimed to
evaluate the phytoextraction and dissipation of lindane by a leafy vegetable
Spinacia oleracea L (Spinach). The test plant was grown in different
concentrations of lindane (5, 10, 15 and 20 mg kg(-1)) and harvested at 10, 30
and 45 days. At 45 days, the concentrations of lindane in root and leaf of
Spinach growing in four different concentrations were reached up to 3.5, 5.4, 7.6
and 12.3 mg kg(-1) and 1.8, 2.2, 3 and 4.9 mg kg(-1), respectively. There was a
significant difference (p<0.01) in the dissipation of lindane in vegetated and
non-vegetated soil. Moreover, the residual lindane in four experiments was
reduced to 81, 76, 69 and 61 percent, respectively. The experimental results
indicate that Spinach can be used for the phytoremediation of lindane. However,
more studies are required to prevent the toxicity of harvested parts.
PMID- 25133348
TI - Antibiotic resistance monitoring in heterotrophic bacteria from anthropogenic
polluted seawater and the intestines of oyster Crassostrea hongkongensis.
AB - A total of 1,050 strains of heterotrophic bacteria isolated from farming seawater
and the intestines of oyster species Crassostrea hongkongensis were tested for
resistance to 10 antibiotics by the Kirby-Bauer diffusion method. The resistant
rates of seawater-derived bacteria to chloramphenicol, enrofloxacin, and
ciprofloxacin were low (less than 20%), whereas the bacteria obtained from
oysters showed low resistance to chloramphenicol and enrofloxacin. Many strains
showed high resistant rates (more than 40%) to furazolidone, penicillin G, and
rifampin. A total of 285 strains from farming seawater and oysters were resistant
to more than three antibiotics. Several strains showed resistance to more than
nine antibiotics. Furthermore, the peak resistant rates of the seawater-derived
strains to multiple antibiotics overlapped in April, June, September, and
November, and those of oyster-derived strains overlapped during April, July, and
September. The multi-resistant rate patterns of strains from farming seawater and
oyster intestines were similar.
PMID- 25133349
TI - An ethically appropriate strategy to combat obesity and food insecurity: the
urban food initiative.
PMID- 25133351
TI - Prognostic value of the Duke treadmill score in octogenarians undergoing
myocardial perfusion imaging.
AB - OBJECTIVES/BACKGROUND: Although Duke treadmill score (DTS) is the most widely
used risk stratification method in younger patients undergoing exercise treadmill
test (ETT) its specific value in the elderly is not established. METHODS: 137
patients aged >=80 years who underwent ETT myocardial perfusion imaging (MPI)
were studied. DTS and MPI (including summed stress scores, SSS) related data were
registered per patient and follow up was performed to document cardiac death
(CD), myocardial infarction (MI) and late (>3 months) revascularization (LR).
Kaplan Meir and Cox regression survival analysis were employed to determine the
prognostic value of DTS in relation to MPI data for these endpoints. RESULTS:
After a median follow up duration of 6.7 years 28 deaths, 7 CDs, 4 non fatal MIs
and 12 LRs were observed. Incidence rates of CD/MI were significantly different
only between low and high risk SSS categories (p = 0.044). Risk groups by DTS had
no significant differences in survival free of CD/MI (p = 0.743) in contrast to
risk groups according to SSS (p = 0.026), while both DTS and SSS based risk
groups had significantly different survival free of CD/MI or LR. SSS was a
significant univariate predictor of both CD/MI (HR 1.088, p = 0.019) and CD/MI or
LR (HR 1.095, p < 0.001), but DTS only of the latter endpoint (HR 0.909, p =
0.003). CONCLUSIONS: In octogenarians DTS was found to be a significant predictor
of the LR related endpoint but not of the hard endpoint of CD/MI, in contrast to
SSS which was a powerful predictor of both soft and hard cardiac endpoints.
PMID- 25133350
TI - Cartilage oligomeric matrix protein (COMP) in murine brachiocephalic and carotid
atherosclerotic lesions.
AB - OBJECTIVE: To investigate the hypothesis that COMP can influence the morphology,
stability and size of murine atherosclerotic lesions. METHODS: ApoE- and
ApoE/COMP-knockout mice were fed a high-fat diet to develop atherosclerotic
plaques at lesion sites of three different types; inflammatory and fibrous
plaques induced in the carotid artery by low or oscillatory shear stress,
respectively, and spontaneously developing plaques in the brachiocephalic artery.
The localization of COMP in the plaques and the effect of COMP deficiency on
plaque development were evaluated. RESULTS: COMP immunoreactivity was observed in
about half of the investigated plaques from the ApoE null mice, mainly located
along the intima-medial border. There were no significant differences in the size
of inflammatory and fibrous carotid plaques between the genotypes. Plaques in the
brachiocephalic artery from ApoE mice lacking COMP were increased in size with
54%. In these plaques the collagen content was also increased by 48%. There were
no differences in relative collagen content in inflammatory and fibrous carotid
plaques between genotypes. Polarized light microscopy showed that the increase in
total collagen in brachiocephalic plaques was more than proportionally accounted
for by an increase in thicker collagen fibrils. CONCLUSION: We have shown that
COMP deficiency has a significant impact on atherosclerotic plaque morphology and
size. Our data also suggest that an altered collagen metabolism may be an
important mechanism in this finding.
PMID- 25133352
TI - Prognostic value of flow-mediated dilation in patients with systemic lupus
erythematosus: a pilot prospective cohort study.
AB - This pilot study evaluated the predictive value of flow-mediated dilation (FMD)
for damage accrual in a cohort of SLE patients. Thirty-eight female SLE patients
without cardiovascular involvement were enrolled. Clinical history, traditional
cardiovascular risk factors, laboratory parameters, disease activity and damage
and brachial artery FMD were collected at study entry and after a mean follow-up
of 4.5 years. At enrollment, 18 patients (47%) presented active disease; mean FMD
was 7.9 +/- 3.1%, with no statistically significant differences between women
with active and inactive disease. During the follow-up, 3 patients died and 14
accrued organ damage. Baseline FMD did not predict death and damage accrual. FMD
showed significant decline over time, which was greater in patients with poor
outcome (-3.9% vs -1.9%, p = 0.03). In conclusion, in a cohort of SLE patients,
baseline FMD was not predictive of damage accrual. However, the latter was
associated with progressive loss of FMD.
PMID- 25133353
TI - Occupational risk factors for low back pain among drivers of three-wheelers in
Sri Lanka.
AB - BACKGROUND: Approximately 5% of all households in Sri Lanka operate a three
wheeler as their primary source of income. However, very little is known about
the occupational health risks associated with driving these vehicles. OBJECTIVES:
The aim of this study was to assess occupational risk factors, including the
number of hours worked associated with the 4-week prevalence of low back pain
(LBP) among drivers of three-wheelers. METHODS: Questionnaires were administered
to 200 full-time drivers of three-wheelers from the Galle District in Sri Lanka.
Occupational, psychological, socio-demographic, lifestyle, and anthropometric
variables were collected. Univariate and multivariate analysis were used to
investigate the correlation between occupational risk factors of the prevalence
of LBP. RESULTS: 15.5% of respondents reported experiencing LBP in the previous 4
months. Univariate analysis revealed that the number of hours worked per week,
feeling pressure to compete with other drivers, and perceived stress scale scores
were significantly associated with the 4-week prevalence of LBP. Multivariate
analysis found that the number of hours worked per week and engine type were
significantly associated with LBP. CONCLUSIONS: LBP is common among drivers of
three-wheelers in Sri Lanka. Long work hours and two-stroke engines were
significantly associated with LBP. Results from this study point towards a role
for educational, behavioral health, and policy interventions to help prevent and
reduce LBP among these drivers.
PMID- 25133354
TI - Structural stability of E. coli trigger factor studied by synchrotron small-angle
X-ray scattering.
AB - Solution small-angle X-ray scattering (SAXS) is an effective technique for
quantitatively measuring the compactness and shape of proteins. We use SAXS to
study the structural characteristics and unfolding transitions induced by urea
for full length Escherichia coli trigger factor (TF) and a series of truncation
mutants, obtaining and comparing the radiuses of gyration (Rg), the distance
distribution function (P(r) function) and integrated intensity of TF variants in
native and unfolding states. The C-terminal 72-residue truncated mutant TF360
exhibited dramatic structural differences and reduced stability compared with the
whole TF molecule, while the N-domain truncated mutant MC maintained its compact
structure with reduced stability. These results indicate that the C-terminal
region of TF plays an important role in the structural and conformational
stabilities of the TF molecule, while the N-domain is relatively independent.
PMID- 25133355
TI - Exit interviews to reduce turnover amongst healthcare professionals.
AB - BACKGROUND: Exit interviews are widely used in healthcare organisations to
identify reasons for staff attrition, yet their usefulness in limiting turnover
is unclear. OBJECTIVES: To determine the effectiveness of various exit interview
strategies in decreasing turnover rates amongst healthcare professionals. SEARCH
METHODS: We searched the Cochrane EPOC Group Specialised Register; Cochrane
Central Register of Controlled Trials (CENTRAL), Issue 11, 2012; MEDLINE, Ovid
(1950- ); EMBASE, Ovid (1947- ); CINAHL, EbscoHost (1980- ), and PsycINFO, OVID
(1806-) between October 31 and November 6, 2012. We also screened the reference
lists of included studies and relevant reviews; and searched trial registries for
planned and on-going studies. We did not restrict searches by language or
publication date. SELECTION CRITERIA: Randomised controlled trials, controlled
clinical trials, controlled before-after studies and interrupted time series
studies comparing turnover rates between healthcare professionals who had
undergone one form of exit interview with another form of exit interview or with
no interview. DATA COLLECTION AND ANALYSIS: Two review authors independently
assessed trial quality and extracted data. MAIN RESULTS: The original search
identified 1560 citations, of which we considered 19 potentially relevant. The
two authors independently reviewed the abstracts of these studies and retrieved
the full texts of eight studies. We excluded all eight following independent
assessment; they were either interviews, commentaries on how to do an exit
interview or descriptive studies about reasons for leaving. We found no studies
that matched our inclusion criteria. For this first update, we screened 2220
citations and identified no new studies. AUTHORS' CONCLUSIONS: Evidence about the
effectiveness of exit interviews to reduce turnover is currently not available.
However, exit interviews may provide useful information about the work
environment which, in turn, may be useful in the development of interventions to
reduce turnover.
PMID- 25133358
TI - Patients' understanding of their hospitalizations and association with
satisfaction.
PMID- 25133360
TI - Atypical antipsychotic drugs and the risk for acute kidney injury and other
adverse outcomes in older adults: a population-based cohort study.
AB - BACKGROUND: Several adverse outcomes attributed to atypical antipsychotic drugs,
specifically quetiapine, risperidone, and olanzapine, are known to cause acute
kidney injury (AKI). Such outcomes include hypotension, acute urinary retention,
and the neuroleptic malignant syndrome or rhabdomyolysis. OBJECTIVE: To
investigate the risk for AKI and other adverse outcomes associated with use of
atypical antipsychotic drugs versus nonuse. DESIGN: Population-based cohort
study. SETTING: Ontario, Canada, from 2003 to 2012. PATIENTS: Adults aged 65
years or older who received a new outpatient prescription for an oral atypical
antipsychotic drug (n=97,777) matched 1:1 with those who did not receive such a
prescription. MEASUREMENTS: The primary outcome was hospitalization with AKI
(assessed by using a hospital diagnosis code and, in a subpopulation, serum
creatinine levels) within 90 days of prescription for atypical antipsychotic
drugs. RESULTS: Atypical antipsychotic drug use versus nonuse was associated with
a higher risk for hospitalization with AKI (relative risk [RR], 1.73 [95% CI,
1.55 to 1.92]). This association was consistent when AKI was assessed in a
subpopulation for which information on serum creatinine levels was available
(5.46% vs. 3.34%; RR, 1.70 [CI, 1.22 to 2.38]; absolute risk increase, 2.12% [CI,
0.80% to 3.43%]). Drug use was also associated with hypotension (RR, 1.91 [CI,
1.60 to 2.28]), acute urinary retention (RR, 1.98 [CI, 1.63 to 2.40]), and all
cause mortality (RR, 2.39 [CI, 2.28 to 2.50]). LIMITATION: Only older adults were
included in the study. CONCLUSION: Atypical antipsychotic drug use is associated
with an increased risk for AKI and other adverse outcomes that may explain the
observed association with AKI. The findings support current safety concerns about
the use of these drugs in older adults. PRIMARY FUNDING SOURCE: Academic Medical
Organization of Southwestern Ontario.
PMID- 25133359
TI - Longevity of patients with cystic fibrosis in 2000 to 2010 and beyond: survival
analysis of the Cystic Fibrosis Foundation patient registry.
AB - BACKGROUND: Advances in treatments for cystic fibrosis (CF) continue to extend
survival. An updated estimate of survival is needed for better prognostication
and to anticipate evolving adult care needs. OBJECTIVE: To characterize trends in
CF survival between 2000 and 2010 and to project survival for children born and
diagnosed with the disease in 2010. DESIGN: Registry-based study. SETTING: 110
Cystic Fibrosis Foundation-accredited care centers in the United States.
PATIENTS: All patients represented in the Cystic Fibrosis Foundation Patient
Registry (CFFPR) between 2000 and 2010. MEASUREMENTS: Survival was modeled with
respect to age, age at diagnosis, gender, race or ethnicity, F508del mutation
status, and symptoms at diagnosis. RESULTS: Between 2000 and 2010, the number of
patients in the CFFPR increased from 21,000 to 26,000, median age increased from
14.3 to 16.7 years, and adjusted mortality decreased by 1.8% per year (95% CI,
0.5% to 2.7%). Males had a 19% (CI, 13% to 24%) lower adjusted risk for death
than females. Median survival of children born and diagnosed with CF in 2010 is
projected to be 37 years (CI, 35 to 39 years) for females and 40 years (CI, 39 to
42 years) for males if mortality remains at 2010 levels and more than 50 years if
mortality continues to decrease at the rate observed between 2000 and 2010.
LIMITATIONS: The CFFPR does not include all patients with CF in the United
States, and loss to follow-up and missing data were observed. Additional analyses
to address these limitations suggest that the survival projections are
conservative. CONCLUSION: Children born and diagnosed with CF in the United
States in 2010 are expected to live longer than those born earlier. This has
important implications for prognostic discussions and suggests that the health
care system should anticipate greater numbers of adults with CF. PRIMARY FUNDING
SOURCE: Cystic Fibrosis Foundation.
PMID- 25133362
TI - Evidence-based risk communication: a systematic review.
AB - BACKGROUND: Effective communication of risks and benefits to patients is critical
for shared decision making. PURPOSE: To review the comparative effectiveness of
methods of communicating probabilistic information to patients that maximize
their cognitive and behavioral outcomes. DATA SOURCES: PubMed (1966 to March
2014) and CINAHL, EMBASE, and the Cochrane Central Register of Controlled Trials
(1966 to December 2011) using several keywords and structured terms. STUDY
SELECTION: Prospective or cross-sectional studies that recruited patients or
healthy volunteers and compared any method of communicating probabilistic
information with another method. DATA EXTRACTION: Two independent reviewers
extracted study characteristics and assessed risk of bias. DATA SYNTHESIS: Eighty
four articles, representing 91 unique studies, evaluated various methods of
numerical and visual risk display across several risk scenarios and with diverse
outcome measures. Studies showed that visual aids (icon arrays and bar graphs)
improved patients' understanding and satisfaction. Presentations including
absolute risk reductions were better than those including relative risk
reductions for maximizing accuracy and seemed less likely than presentations with
relative risk reductions to influence decisions to accept therapy. The
presentation of numbers needed to treat reduced understanding. Comparative
effects of presentations of frequencies (such as 1 in 5) versus event rates
(percentages, such as 20%) were inconclusive. LIMITATION: Most studies were small
and highly variable in terms of setting, context, and methods of administering
interventions. CONCLUSION: Visual aids and absolute risk formats can improve
patients' understanding of probabilistic information, whereas numbers needed to
treat can lessen their understanding. Due to study heterogeneity, the superiority
of any single method for conveying probabilistic information is not established,
but there are several good options to help clinicians communicate with patients.
PRIMARY FUNDING SOURCE: None.
PMID- 25133363
TI - Cystic fibrosis: recent successes present new challenges.
PMID- 25133364
TI - Inside special care.
PMID- 25133365
TI - Aggregate cost of mammography screening in the United States.
PMID- 25133366
TI - Aggregate cost of mammography screening in the United States.
PMID- 25133367
TI - Aggregate cost of mammography screening in the United States.
PMID- 25133368
TI - Prescription drug abuse.
PMID- 25133369
TI - Prescription drug abuse.
PMID- 25133370
TI - Prescription drug abuse.
PMID- 25133371
TI - The dueling obligations of opioid stewardship.
PMID- 25133372
TI - The dueling obligations of opioid stewardship.
PMID- 25133375
TI - Summaries for patients. Improved survival of patients with cystic fibrosis.
PMID- 25133376
TI - Web Exclusives. The consult guys--is that hemoglobin high enough?
PMID- 25133377
TI - ACP Journal Club. Review: Natriuretic peptide-guided therapy reduces mortality
more than clinically guided therapy in heart failure.
PMID- 25133378
TI - ACP Journal Club. Review: Self-collected samples are less accurate for HPV
testing than clinician-collected samples.
PMID- 25133379
TI - ACP Journal Club. ACC/AHA Pooled Cohort Risk Equations predicted 5-y risk for CV
events in adults considered for statin initiation.
PMID- 25133380
TI - ACP Journal Club. ACC/AHA, Adult Treatment Panel III, and ESC guidelines
overestimated risk for CVD in older adults.
PMID- 25133381
TI - ACP Journal Club. Review: In diabetes, ACE-Is, but not ARBs, reduce mortality and
major CV events compared with placebo or active treatment.
PMID- 25133382
TI - ACP Journal Club. In uncontrolled type 2 diabetes, CBT improved glycemic control
and reduced depression.
PMID- 25133383
TI - ACP Journal Club. Bariatric surgery improved HbA1c more than intensive medical
therapy in obese patients with uncontrolled type 2 DM.
PMID- 25133384
TI - ACP Journal Club. In noncardiac surgery, perioperative aspirin did not reduce
death or MI at 30 d but increased major bleeding.
PMID- 25133385
TI - ACP Journal Club. Methotrexate reduced pain and improved function in symptomatic
knee osteoarthritis.
PMID- 25133386
TI - ACP Journal Club. In atrial fibrillation, dabigatran had similar efficacy to
warfarin but caused less bleeding in higher GFR.
PMID- 25133387
TI - ACP Journal Club. Review: In COPD, fluticasone or budesonide increases serious
pneumonia but not mortality.
PMID- 25133388
TI - ACP Journal Club. Review: Selective digestive decontamination reduces mortality
more than chlorhexidine in general ICU patients.
PMID- 25133390
TI - Nanoscale Diblock copolymer micelles: characterizations and estimation of the
effective diffusion coefficients of biomolecules release through cylindrical
diffusion model.
AB - Biomolecules have been widely investigated as potential therapeutics for various
diseases. However their use is limited due to rapid degradation and poor cellular
uptake in vitro and in vivo. To address this issue, we synthesized a new nano
carrier system comprising of cholic acid-polyethylenimine (CA-PEI) copolymer
micelles, via carbodiimide-mediated coupling for the efficient delivery of small
interfering ribonucleic acid (siRNA) and bovine serum albumin (BSA) as model
protein. The mean particle size of siRNA- or BSA-loaded CA-PEI micelles ranged
from 100-150 nm, with zeta potentials of +3-+11 mV, respectively. Atomic force,
transmission electron and field emission scanning electron microscopy
demonstrated that the micelles exhibited excellent spherical morphology. No
significant morphology or size changes were observed in the CA-PEI micelles after
siRNA and BSA loading. CA-PEI micelles exhibited sustained release profile, the
effective diffusion coefficients were successfully estimated using a
mathematically-derived cylindrical diffusion model and the release data of siRNA
and BSA closely fitted into this model. High siRNA and BSA binding and loading
efficiencies (95% and 70%, respectively) were observed for CA-PEI micelles.
Stability studies demonstrated that siRNA and BSA integrity was maintained after
loading and release. The CA-PEI micelles were non cytotoxic to V79 and DLD-1
cells, as shown by alamarBlue and LIVE/DEAD cell viability assays. RT-PCR study
revealed that siRNA-loaded CA-PEI micelles suppressed the mRNA for ABCB1 gene.
These results revealed the promising potential of CA-PEI micelles as a stable,
safe, and versatile nano-carrier for siRNA and the model protein delivery.
PMID- 25133389
TI - Efficacy and day 7 plasma piperaquine concentrations in African children treated
for uncomplicated malaria with dihydroartemisinin-piperaquine.
AB - BACKGROUND: One promising new Artemisinin-based combination therapies (ACTs) is
dihydroartemisinin-piperaquine (DHA-PQ). However, the pharmacokinetics of
piperaquine and the relationship between drug levels and clinical efficacy are
incompletely characterized, particularly in children. METHODS: We performed a
single-arm open-label trial in Bobo-Dioulasso, Burkina Faso. A total of 379
participants aged 6 months or more with uncomplicated falciparum malaria were
enrolled. Each participant received daily dose of DHA-PQ for three days and
followed for 42 days. Parasitological efficacy was analyzed, considering rates of
recrudescence and overall recurrence. PK was an exploratory endpoint and a
priori, no sample size had been determined. Day 7 capillary and venous plasma
concentrations of piperaquine were measured in children aged 2-10 years. RESULTS:
Of the 379 participants, 365 (96.3%) completed 42 days of follow-up. The median
daily dose of PQ was 18.5 mg/kg [6.5-24]. Treatment with DHA-PQ was well
tolerated with fever and parasitemia resolution within 48 hours in nearly all
children. Recurrent malaria within 42 days of follow-up occurred in 31.3% (10/34)
of children less than 2 years old, 16.0% (16/106) of those aged 2-5 years, 9.4%
(15/160) of those aged 5-10 years, and none (0/68) of those over 10 years old.
After genotyping, 3 of 41 recurrent episodes were recrudescence. An exploratory
analysis shows that children with successful treatment outcomes had significantly
higher median plasma concentrations of PQ compared to those with recurrent
malaria within 42 days after therapy, considering either capillary samples (68
ng/ml [50-85] compared to 48 ng/ml [36-55], p<0.001) or venous samples (42 ng/ml
[29-59] compared to 25 ng/ml [19-44], p<0.001). CONCLUSION: DHA-PQ was effective
for uncomplicated P. falciparum malaria treatment and offers an alternative to
other ACTs. Recurrent malaria was mainly due to new infections after treatment
and was correlated with low day 7 PQ concentration in the youngest patients.
TRIAL REGISTRATION: Controlled-Trials.com ISRCTN59761234.
PMID- 25133391
TI - A rank-based sequence aligner with applications in phylogenetic analysis.
AB - Recent tools for aligning short DNA reads have been designed to optimize the
trade-off between correctness and speed. This paper introduces a method for
assigning a set of short DNA reads to a reference genome, under Local Rank
Distance (LRD). The rank-based aligner proposed in this work aims to improve
correctness over speed. However, some indexing strategies to speed up the aligner
are also investigated. The LRD aligner is improved in terms of speed by storing
[Formula: see text]-mer positions in a hash table for each read. Another
improvement, that produces an approximate LRD aligner, is to consider only the
positions in the reference that are likely to represent a good positional match
of the read. The proposed aligner is evaluated and compared to other state of the
art alignment tools in several experiments. A set of experiments are conducted to
determine the precision and the recall of the proposed aligner, in the presence
of contaminated reads. In another set of experiments, the proposed aligner is
used to find the order, the family, or the species of a new (or unknown)
organism, given only a set of short Next-Generation Sequencing DNA reads. The
empirical results show that the aligner proposed in this work is highly accurate
from a biological point of view. Compared to the other evaluated tools, the LRD
aligner has the important advantage of being very accurate even for a very low
base coverage. Thus, the LRD aligner can be considered as a good alternative to
standard alignment tools, especially when the accuracy of the aligner is of high
importance. Source code and UNIX binaries of the aligner are freely available for
future development and use at http://lrd.herokuapp.com/aligners. The software is
implemented in C++ and Java, being supported on UNIX and MS Windows.
PMID- 25133393
TI - MiR-152 may silence translation of CaMK II and induce spontaneous immune
tolerance in mouse liver transplantation.
AB - Spontaneous immune tolerance in mouse liver transplantation has always been a
hotspot in transplantation-immune research. Recent studies revealed that
regulatory T cells (Tregs), hepatic satellite cells and Kupffer cells play a
potential role in spontaneous immune tolerance, however the precise mechanism of
spontaneous immune tolerance is still undefined. By using Microarray Chips, we
investigated different immune regulatory factors to decipher critical mechanisms
of spontaneous tolerance after mouse liver transplantation. Allogeneic (C57BL/6
C3H) and syngeneic (C3H-C3H) liver transplantation were performed by 6-8 weeks
old male C57BL/6 and C3H mice. Graft samples (N = 4 each group) were collected
from 8 weeks post-operation mice. 11 differentially expressed miRNAs in
allogeneic grafts (Allografts) vs. syngeneic grafts (Syngrafts) were identified
using Agilent Mouse miRNA Chips. It was revealed that 185 genes were modified by
the 11 miRNAs, furthermore, within the 185 target genes, 11 of them were tightly
correlated with immune regulation after Gene Ontology (GO), Kyoto Encyclopedia of
Genes and Genomes (KEGG) analysis and Genbank data cross-comparison. Verified by
real-time PCR and western blot, our results indicated that mRNA expression levels
of IL-6 and TAB2 were respectively down regulated following miR-142-3p and miR
155 augment. In addition, increased miR-152 just silenced mRNA of CaMK II and
down-regulated translation of CaMK II in tolerated liver grafts, which may play a
critical role in immune regulation and spontaneous tolerance induction of mouse
liver transplantation.
PMID- 25133392
TI - Pyridostigmine restores cardiac autonomic balance after small myocardial
infarction in mice.
AB - The effect of pyridostigmine (PYR)--an acetylcholinesterase inhibitor--on
hemodynamics and cardiac autonomic control, was never studied in conscious
myocardial infarcted mice. Telemetry transmitters were implanted into the carotid
artery under isoflurane anesthesia. Seven to ten days after recovery from the
surgery, basal arterial pressure and heart rate were recorded, while
parasympathetic and sympathetic tone (DeltaHR) was evaluated by means of methyl
atropine and propranolol. After the basal hemodynamic recording the mice were
subjected to left coronary artery ligation for producing myocardial infarction
(MI), or sham operation, and implantation of minipumps filled with PYR or saline.
Separate groups of anesthetized (isoflurane) mice previously (4 weeks) subjected
to MI, or sham coronary artery ligation, were submitted to cardiac function
examination. The mice exhibited an infarct length of approximately 12%, no change
in arterial pressure and increased heart rate only in the 1st week after MI.
Vagal tone decreased in the 1st week, while the sympathetic tone was increased in
the 1st and 4th week after MI. PYR prevented the increase in heart rate but did
not affect the arterial pressure. Moreover, PYR prevented the increase in
sympathetic tone throughout the 4 weeks. Concerning the parasympathetic tone, PYR
not only impaired its attenuation in the 1st week, but enhanced it in the 4th
week. MI decreased ejection fraction and increased diastolic and systolic volume.
Therefore, the pharmacological increase of peripheral acetylcholine availability
by means of PYR prevented tachycardia, increased parasympathetic and decreased
sympathetic tone after MI in mice.
PMID- 25133394
TI - Characterisation of SalRAB a salicylic acid inducible positively regulated efflux
system of Rhizobium leguminosarum bv viciae 3841.
AB - Salicylic acid is an important signalling molecule in plant-microbe defence and
symbiosis. We analysed the transcriptional responses of the nitrogen fixing plant
symbiont, Rhizobium leguminosarum bv viciae 3841 to salicylic acid. Two MFS-type
multicomponent efflux systems were induced in response to salicylic acid, rmrAB
and the hitherto undescribed system salRAB. Based on sequence similarity salA and
salB encode a membrane fusion and inner membrane protein respectively. salAB are
positively regulated by the LysR regulator SalR. Disruption of salA significantly
increased the sensitivity of the mutant to salicylic acid, while disruption of
rmrA did not. A salA/rmrA double mutation did not have increased sensitivity
relative to the salA mutant. Pea plants nodulated by salA or rmrA strains did not
have altered nodule number or nitrogen fixation rates, consistent with weak
expression of salA in the rhizosphere and in nodule bacteria. However, BLAST
analysis revealed seventeen putative efflux systems in Rlv3841 and several of
these were highly differentially expressed during rhizosphere colonisation, host
infection and bacteroid differentiation. This suggests they have an integral role
in symbiosis with host plants.
PMID- 25133395
TI - Cost of disorders of the brain in Spain.
AB - BACKGROUND: Brain disorders represent a high burden in Europe and worldwide. The
objective of this study was to provide specific estimates of the economic costs
of brain disorders in Spain, based on published epidemiological and economic
evidence. METHODS: A cost-of-illness study with a societal perspective of 19
brain disorders was carried out. Cost data published between 2004 and 2012 was
obtained from a systematic literature review. Direct healthcare, direct non
medical and indirect costs were considered, prioritizing bottom-up information.
All costs were converted to Euro and to year 2010. The missing values were
imputed with European estimates. Sensitivity analyses based on qualitative
assessment of the literature and on a Monte Carlo simulation were performed.
RESULTS: The review identified 33 articles with information on costs for 11
disorders (8 neurological, 3 mental). The average per-patient cost ranged from
36,946 ? for multiple sclerosis to 402 ? for headache. The societal cost of the
19 brain disorders in Spain in 2010 was estimated in 84 ? billion. Societal costs
ranged from 15 ? billion for dementia to 65 ? million for eating disorders.
Mental disorders societal cost were 46 ? billions (55% of the total), while
neurological disorder added up to 38 ? billion. Healthcare costs represented 37%
of the societal costs of brain disorders, whereas direct non-medical constituted
29% and indirect costs 33%. CONCLUSION: Brain disorders have a substantial
economic impact in Spain (equivalent to almost 8% of the country's GDP). Economic
data on several important brain disorders, specially mental disorders, is still
sparse.
PMID- 25133396
TI - Differential modulation by IL-17A of Cholangitis versus Colitis in IL-2Ralpha
deleted mice.
AB - IFN-gamma is a signature Th1 cell associated cytokine critical for the
inflammatory response in autoimmunity with both pro-inflammatory and potentially
protective functions. IL-17A is the hallmark of T helper 17 (Th17) cell subsets,
produced by gammadeltaT, CD8+ T, NK and NKT cells. We have taken advantage of our
colony of IL-2Ralpha-/- mice that spontaneously develop both autoimmune
cholangitis and inflammatory bowel disease. In this model CD8+ T cells mediate
biliary ductular damage, whereas CD4+ T cells mediate induction of colon-specific
autoimmunity. Importantly, IL-2Ralpha-/- mice have high levels of interferon
gamma (IFN-gamma), and interleukin-17A (IL-17A). We produced unique double
deletions of mice that were either IL-17A-/-IL-2Ralpha-/- or IFN-gamma-/-IL
2Ralpha-/- to specifically address the precise role of these two cytokines in the
natural history of autoimmune cholangitis and colitis. Of note, deletion of IL
17A in IL-2Ralpha-/- mice led to more severe liver inflammation, but ameliorated
colitis. In contrast, there were no significant changes in the immunopathology of
double knock-out IFN-gamma-/- IL-2Ralpha-/- mice, compared to single knock-out IL
2Ralpha-/- mice with respect to cholangitis or colitis. Furthermore, there was a
significant increase in pathogenetic CD8+ T cells in the liver of IL-17A-/-IL
2Ralpha-/- mice. Our data suggest that while IL-17A plays a protective role in
autoimmune cholangitis, it has a pro-inflammatory role in inflammatory bowel
disease. These data take on particular significance in the potential use of anti
IL-17A therapy in humans with primary biliary cirrhosis.
PMID- 25133397
TI - Operative rigid bronchoscopy: indications, basic techniques and results.
AB - Palliative airway treatments are essential to improve quality and length of life
in lung cancer patients with central airway obstruction. Rigid bronchoscopy has
proved to be an excellent tool to provide airway access and control in this
cohort of patients. The main indication for rigid bronchoscopy in adult
bronchology remains central airway obstruction due to neoplastic or non
neoplastic disease. We routinely use negative pressure ventilation (NPV) under
general anaesthesia to prevent intraoperative apnoea and respiratory acidosis.
This procedure allows opioid sparing, a shorter recovery time and avoids manually
assisted ventilation, thereby reducing the amount of oxygen needed, while
maintaining optimal surgical conditions. The major indication for NPV rigid
bronchoscopy at our institution has been airway obstruction by neoplastic
tracheobronchial tissue, mainly treated by laser-assisted mechanical dissection.
When strictly necessary, we use silicone stents for neoplastic or cicatricial
strictures, reserving metal stents to cover tracheo-oesophageal fistulae. NPV
rigid bronchoscopy is an excellent tool for the endoscopic treatment of locally
advanced tumours of the lung, especially when patients have exhausted the
conventional therapeutic resources. Laser-assisted mechanical resection and stent
placement are the most effective procedures for preserving quality of life in
patients with advanced stage cancer.
PMID- 25133400
TI - Proteomics-identified Bvg-activated autotransporters protect against bordetella
pertussis in a mouse model.
AB - Pertussis is a highly infectious respiratory disease of humans caused by the
bacterium Bordetella pertussis. Despite high vaccination coverage, pertussis has
re-emerged globally. Causes for the re-emergence of pertussis include limited
duration of protection conferred by acellular pertussis vaccines (aP) and
pathogen adaptation. Pathogen adaptations involve antigenic divergence with
vaccine strains, the emergence of strains which show enhanced in vitro expression
of a number of virulence-associated genes and of strains that do not express
pertactin, an important aP component. Clearly, the identification of more
effective B. pertussis vaccine antigens is of utmost importance. To identify
novel antigens, we used proteomics to identify B. pertussis proteins regulated by
the master virulence regulatory system BvgAS in vitro. Five candidates proteins
were selected and it was confirmed that they were also expressed in the lungs of
naive mice seven days after infection. The five proteins were expressed in
recombinant form, adjuvanted with alum and used to immunize mice as stand-alone
antigens. Subsequent respiratory challenge showed that immunization with the
autotransporters Vag8 and SphB1 significantly reduced bacterial load in the
lungs. Whilst these antigens induced strong opsonizing antibody responses, we
found that none of the tested alum-adjuvanted vaccines - including a three
component aP - reduced bacterial load in the nasopharynx, suggesting that
alternative immunological responses may be required for efficient bacterial
clearance from the nasopharynx.
PMID- 25133401
TI - Antioxidant and antiproliferative activities of twenty-four Vitis vinifera
grapes.
AB - Grapes are rich in phytochemicals with many proven health benefits. Phenolic
profiles, antioxidant and antiproliferative activities of twenty-four selected
Vitis vinifera grape cultivars were investigated in this study. Large ranges of
variation were found in these cultivars for the contents of total phenolics (95.3
to 686.5 mg/100 g) and flavonoids (94.7 to 1055 mg/100 g) and antioxidant
activities (oxygen radical absorbance capacity 378.7 to 3386.0 mg of Trolox
equivalents/100 g and peroxylradical scavenging capacity14.2 to 557 mg of vitamin
C equivalents/100 g), cellular antioxidant activities (3.9 to 139.9 umol of
quercetin equivalents/100 g without PBS wash and 1.4 to 95.8 umol of quercetin
equivalents /100 g with PBS wash) and antiproliferative activities (25 to 82% at
the concentrations of 100 mg/mL extracts).The total antioxidant activities were
significantly correlated with the total phenolics and flavonoids. However, no
significant correlations were found between antiproliferative activities and
total phenolics or total flavonoids content. Wine grapes and color grapes showed
much higher levels of phytochemicals and antioxidant activities than table grapes
and green/yellow grapes. Several germplasm accessions with much high contents of
phenolics and flavonoids, and total antioxidant activity were identified. These
germplasm can be valuable sources of genes for breeding grape cultivars with
better nutritional qualities of wine and table grapes in the future.
PMID- 25133402
TI - Comparative proteomics of milk fat globule membrane proteins from transgenic
cloned cattle.
AB - The use of transgenic livestock is providing new methods for obtaining
pharmaceutically useful proteins. However, the protein expression profiles of the
transgenic animals, including expression of milk fat globule membrane (MFGM)
proteins, have not been well characterized. In this study, we compared the MFGM
protein expression profile of the colostrum and mature milk from three lines of
transgenic cloned (TC) cattle, i.e., expressing recombinant human alpha
lactalbumin (TC-LA), lactoferrin (TC-LF) or lysozyme (TC-LZ) in the mammary
gland, with those from cloned non-transgenic (C) and conventionally bred normal
animals (N). We identified 1, 225 proteins in milk MFGM, 166 of which were
specifically expressed only in the TC-LA group, 265 only in the TC-LF group, and
184 only in the TC-LZ group. There were 43 proteins expressed only in the
transgenic cloned animals, but the concentrations of these proteins were below
the detection limit of silver staining. Functional analysis also showed that the
43 proteins had no obvious influence on the bovine mammary gland. Quantitative
comparison revealed that MFGM proteins were up- or down-regulated more than
twofold in the TC and C groups compared to N group: 126 in colostrum and 77 in
mature milk of the TC-LA group; 157 in colostrum and 222 in mature milk of the TC
LF group; 49 in colostrum and 98 in mature milk of the TC-LZ group; 98 in
colostrum and 132 in mature milk in the C group. These up- and down-regulated
proteins in the transgenic animals were not associated with a particular
biological function or pathway, which appears that expression of certain
exogenous proteins has no general deleterious effects on the cattle mammary
gland.
PMID- 25133403
TI - Hydrocortisone fails to abolish NF-kappaB1 protein nuclear translocation in
deletion allele carriers of the NFKB1 promoter polymorphism (-94ins/delATTG) and
is associated with increased 30-day mortality in septic shock.
AB - BACKGROUND: Previous investigations and meta-analyses on the effect of
glucocorticoids on mortality in septic shock revealed mixed results. This
heterogeneity might be evoked by genetic variations. Such candidate is a promoter
polymorphism (-94ins/delATTG) of the gene encoding the ubiquitous transcription
factor nuclear-factor-kappaB (NF-kappaB) which binds to recognition elements in
the promoter of several genes encoding for the innate immune-system. In turn,
hydrocortisone inhibits NF-kappaB nuclear translocation and thus transcription of
key immune-response regulators. Accordingly, we tested the hypotheses that
hydrocortisone has a NFKB1 genotype dependent effect on 1) NF-kappaB1 nuclear
translocation evoked by lipopolysaccharide (LPS) in monocytes in vitro, and 2)
mortality in septic shock. METHODS: Monocytes of volunteers with the homozygous
insertion (II; n = 5) or deletion (DD; n = 6) NFKB1 genotype were incubated with
10 ugml-1 LPS +/- hydrocortisone (10-5M), and NF-kappaB1 nuclear translocation
was assessed (immunofluorescence). Furthermore, we analyzed 30-day-mortality in
160 patients with septic shock stratified for both genotype and hydrocortisone
therapy. RESULTS: Hydrocortisone inhibited LPS induced nuclear translocation of
NF-kappaB1 in II (25%+/-11;p = 0.0001) but not in DD genotypes (51%+/-15;p =
n.s.). Onehundredandfour of 160 patients with septic shock received
hydrocortisone, at the discretion of the intensivist. NFKB1 deletion allele
carriers (ID/DD) receiving hydrocortisone had a much greater 30-day-mortality
(57.6%) than II genotypes (24.4%; HR:3.18, 95%-CI:1.61-6.28;p = 0.001). In
contrast, 30-day mortality was 22.2% in ID/DD and 25.0% in II genotypes without
hydrocortisone therapy. Results were similar when using propensity score matching
to account for possible bias in the intensivists' decision to administer
hydrocortisone. CONCLUSION: Hydrocortisone fails to inhibit LPS induced nuclear
NF-kappaB1 translocation in deletion allele carriers of the NFKB1 promoter
polymorphism (-94ins/delATTG). In septic shock, hydrocortisone treatment is
associated with markedly increased 30-day-mortality only in such carriers.
Accordingly, previous heterogeneous results regarding the benefit of
hydrocortisone in septic shock may be reconciled by genetic variation of the
NFKB1 promoter polymorphism.
PMID- 25133404
TI - Distinctly different dynamics and kinetics of two steroid receptors at the same
response elements in living cells.
AB - Closely related transcription factors (TFs) can bind to the same response
elements (REs) with similar affinities and activate transcription. However, it is
unknown whether transcription is similarly orchestrated by different TFs bound at
the same RE. Here we have compared the recovery half time (t1/2), binding site
occupancy and the resulting temporal changes in transcription upon binding of two
closely related steroid receptors, the androgen and glucocorticoid receptors (AR
and GR), to their common hormone REs (HREs). We show that there are significant
differences at all of these levels between AR and GR at the MMTV HRE when
activated by their ligands. These data show that two TFs bound at the same RE can
have significantly different modes of action that can affect their responses to
environmental cues.
PMID- 25133407
TI - Identification of Trueperella pyogenes isolated from bovine mastitis by Fourier
transform infrared spectroscopy.
AB - The present study was designed to investigate the potential of Fourier transform
infrared (FT-IR) spectroscopy to identify Trueperella (T.) pyogenes isolated from
bovine clinical mastitis. FT-IR spectroscopy was applied to 57 isolates obtained
from 55 cows in a period from 2009 to 2012. Prior to FT-IR spectroscopy these
isolates were identified by phenotypic and genotypic properties, also including
the determination of seven potential virulence factor encoding genes. The FT-IR
analysis revealed a reliable identification of all 57 isolates as T. pyogenes and
a clear separation of this species from the other species of genus Trueperella
and from species of genus Arcanobacterium and Actinomyces. The results showed
that all 57 isolates were assigned to the correct species indicating that FT-IR
spectroscopy could also be efficiently used for identification of this bacterial
pathogen.
PMID- 25133408
TI - Workplace discrimination predicting racial/ethnic socialization across African
American, Latino, and Chinese families.
AB - Informed by Kohn and Schooler's (1969) occupational socialization framework, this
study examined linkages between racial/ethnic minority mothers' perceptions of
racial/ethnic discrimination in the workplace and adolescents' accounts of
racial/ethnic socialization in the home. Data were collected from 100 mother
early adolescent dyads who participated in a longitudinal study of urban
adolescents' development in the Northeastern United States, including African
American, Latino, and Chinese families. Mothers and adolescents completed surveys
separately. We found that when mothers reported more frequent institutional
discrimination at work, adolescents reported more frequent preparation for bias
messages at home, across racial/ethnic groups. Mothers' experiences of
interpersonal prejudice at work were associated with more frequent cultural
socialization messages among African American and Latino families. Chinese youth
reported fewer cultural socialization messages when mothers perceived more
frequent interpersonal prejudice at work. Findings are discussed in the context
of minority groups' distinct social histories and economic status in the United
States.
PMID- 25133409
TI - Selective incivility: immigrant groups experience subtle workplace discrimination
at different rates.
AB - Immigrants play an increasingly important role in local labor markets. Not only
do they grow steadily in number but also in cultural, educational, and skill
diversity, underlining the necessity to distinguish between immigrant groups when
studying discrimination against immigrants. We examined immigrant employees'
subtle discrimination experiences in a representative sample in Switzerland,
controlling for dispositional influences. Results showed that mainly members of
highly competitive immigrant groups, from immediate neighbor countries,
experienced workplace incivility and that these incivility experiences were
related to higher likelihoods of perceived discrimination at work. This research
confirms recent accounts that successful but disliked groups are particularly
likely to experience subtle interpersonal discrimination.
PMID- 25133410
TI - The acculturation gap-distress model: Extensions and application to Arab Canadian
families.
AB - Using a multidomain and bidimensional approach, the present study applied and
extended the acculturation gap-distress model with an immigrant Arab Canadian
sample. Consistent with this model, immigrant Arab emerging adults (n = 113)
perceived acculturation gaps between themselves and their parents with respect to
their heritage and settlement culture orientation and values. Some of these gaps,
in turn, were associated with poorer outcomes. Extending the model, the most
problematic acculturation gaps were those in which the emerging adult perceived
themselves to be more oriented to Arab culture and values than their parents. We
also found some support for the moderating role of parent-emerging adult
relationships.
PMID- 25133405
TI - Cardiac sympathetic denervation in 6-OHDA-treated nonhuman primates.
AB - Cardiac sympathetic neurodegeneration and dysautonomia affect patients with
sporadic and familial Parkinson's disease (PD) and are currently proposed as
prodromal signs of PD. We have recently developed a nonhuman primate model of
cardiac dysautonomia by iv 6-hydroxydopamine (6-OHDA). Our in vivo findings
included decreased cardiac uptake of a sympathetic radioligand and circulating
catecholamines; here we report the postmortem characterization of the model. Ten
adult rhesus monkeys (5-17 yrs old) were used in this study. Five animals
received 6-OHDA (50 mg/kg i.v.) and five were age-matched controls. Three months
post-neurotoxin the animals were euthanized; hearts and adrenal glands were
processed for immunohistochemistry. Quantification of immunoreactivity (ir) of
stainings was performed by an investigator blind to the treatment group using NIH
ImageJ software (for cardiac bundles and adrenals, area above threshold and
optical density) and MBF StereoInvestigator (for cardiac fibers, area fraction
fractionator probe). Sympathetic cardiac nerve bundle analysis and fiber area
density showed a significant reduction in global cardiac tyrosine hydroxylase-ir
(TH; catecholaminergic marker) in 6-OHDA animals compared to controls.
Quantification of protein gene protein 9.5 (pan-neuronal marker) positive cardiac
fibers showed a significant deficit in 6-OHDA monkeys compared to controls and
correlated with TH-ir fiber area. Semi-quantitative evaluation of human leukocyte
antigen-ir (inflammatory marker) and nitrotyrosine-ir (oxidative stress marker)
did not show significant changes 3 months post-neurotoxin. Cardiac nerve bundle
alpha-synuclein-ir (presynaptic protein) was reduced (trend) in 6-OHDA treated
monkeys; insoluble proteinase-K resistant alpha-synuclein (typical of PD
pathology) was not observed. In the adrenal medulla, 6-OHDA monkeys had
significantly reduced TH-ir and aminoacid decarboxylase-ir. Our results confirm
that systemic 6-OHDA dosing to nonhuman primates induces cardiac sympathetic
neurodegeneration and loss of catecholaminergic enzymes in the adrenal medulla,
and suggests that this model can be used as a platform to evaluate disease
modifying strategies aiming to induce peripheral neuroprotection.
PMID- 25133411
TI - Identity threat at work: how social identity threat and situational cues
contribute to racial and ethnic disparities in the workplace.
AB - Significant disparities remain between racial and ethnic minorities' and Whites'
experiences of American workplaces. Traditional prejudice and discrimination
approaches explain these gaps in hiring, promotion, satisfaction, and well-being
by pointing to the prejudice of people within organizations such as peers,
managers, and executives. Grounded in social identity threat theory, this
theoretical review instead argues that particular situational cues-often
communicated by well-meaning, largely unprejudiced employees and managers-signal
to stigmatized groups whether their identity is threatened and devalued or
respected and affirmed. First, we provide an overview of how identity threat
shapes the psychological processes of racial and ethnic minorities by heightening
vigilance to certain situational cues in the workplace. Next, we outline several
of these cues and their role in creating and sustaining perceptions of identity
threat (or safety). Finally, we provide empirically grounded suggestions that
organizations may use to increase identity safety among their employees of color.
Taken together, the research demonstrates how situational cues contribute to
disparate psychological experiences for racial and ethnic minorities at work, and
suggests that by altering threatening cues, organizations may create more
equitable, respectful, and inclusive environments where all people may thrive.
PMID- 25133412
TI - Chinese American immigrant parents' emotional expression in the family: Relations
with parents' cultural orientations and children's emotion-related regulation.
AB - The present study examined 2 measures of Chinese American immigrant parents'
emotional expression in the family context: self-reported emotional expressivity
and observed emotional expression during a parent-child interaction task. Path
analyses were conducted to examine the concurrent associations between measures
of emotional expression and (a) parents' American and Chinese cultural
orientations in language proficiency, media use, and social affiliation domains,
and (b) parents' and teachers' ratings of children's emotion-related regulation.
Results suggested that cultural orientations were primarily associated with
parents' self-reported expressivity (rather than observed emotional expression),
such that higher American orientations were generally associated with higher
expressivity. Although parents' self-reported expressivity was only related to
their own reports of children's regulation, parents' observed emotional
expression was related to both parents' and teachers' reports of children's
regulation. These results suggest that self-reported expressivity and observed
emotional expression reflect different constructs and have differential relations
to parents' cultural orientations and children's regulation.
PMID- 25133413
TI - A randomized controlled trial to promote volunteering in older adults.
AB - Volunteering is presumed to confer health benefits, but interventions to
encourage older adults to volunteer are sparse. Therefore, a randomized
controlled trial with 280 community-dwelling older German adults was conducted to
test the effects of a theory-based social-cognitive intervention against a
passive waiting-list control group and an active control intervention designed to
motivate physical activity. Self-reports of weekly volunteering minutes were
assessed at baseline (5 weeks before the intervention) as well as 2 and 6 weeks
after the intervention. Participants in the treatment group increased their
weekly volunteering minutes to a greater extent than participants in the control
groups 6 weeks after the intervention. We conclude that a single, face-to-face
group session can increase volunteering among older community-dwelling adults.
However, the effects need some time to unfold because changes in volunteering
were not apparent 2 weeks after the intervention.
PMID- 25133415
TI - Longitudinal associations between activity and cognition vary by age, activity
type, and cognitive domain.
AB - The demonstration of correlated change is critical to understanding the
relationship between activity engagement and cognitive functioning in older
adulthood. Changes in activity have been shown to be related to changes in
cognition, but little attention has been devoted to how this relationship may
vary between specific activity types, cognitive domains, and age groups.
Participants initially aged 65-98 years (M = 77.46 years) from the Australian
Longitudinal Study of Ageing (n = 1,321) completed measurements of activity
(i.e., cognitive, group social, one-on-one social, and physical) and cognition
(i.e., perceptual speed, and immediate and delayed episodic memory) at baseline,
2, 8, 11, and 15 years later. Bivariate latent growth curve models covarying for
education, sex, and baseline age and medical conditions revealed multiple
positive-level relations between activity and cognitive performance, but activity
level was not related to later cognitive change. Change in perceptual speed over
15 years was positively associated with change in cognitive activity, and change
in immediate episodic memory was positively associated with change in one-on-one
social activity. Old-old adults showed a stronger change-change covariance for
mentally stimulating activity in relation to perceptual speed than did young-old
adults. The differentiation by activity type, cognitive domain, and age
contributes to the growing evidence that there is variation in the way cognitive
ability at different ages is related to activity.
PMID- 25133414
TI - Why does placement of persons with Alzheimer's disease into long-term care
improve caregivers' well-being? Examination of psychological mediators.
AB - Caregiving for individuals with Alzheimer's disease is associated with chronic
stress and elevated symptoms of depression. Placement of the care receiver (CR)
into a long-term care setting may be associated with improved caregiver well
being; however, the psychological mechanisms underlying this relationship are
unclear. This study evaluated whether decreases in activity restriction and
increases in personal mastery mediated placement-related reductions in caregiver
depressive symptoms. In a 5-year longitudinal study of 126 spousal Alzheimer's
disease caregivers, we used multilevel models to evaluate placement-related
changes in depressive symptoms (short form of the Center for Epidemiologic
Studies Depression scale), activity restriction (Activity Restriction Scale), and
personal mastery (Pearlin Mastery Scale) in 44 caregivers who placed their
spouses into long-term care relative to caregivers who never placed their CRs.
The Monte Carlo method for assessing mediation was used to evaluate the
significance of the indirect effect of activity restriction and personal mastery
on postplacement changes in depressive symptoms. Placement of the CR was
associated with significant reductions in depressive symptoms and activity
restriction and was also associated with increased personal mastery. Lower
activity restriction and higher personal mastery were associated with reduced
depressive symptoms. Furthermore, both variables significantly mediated the
effect of placement on depressive symptoms. Placement-related reductions in
activity restriction and increases in personal mastery are important
psychological factors that help explain postplacement reductions in depressive
symptoms. The implications for clinical care provided to caregivers are
discussed.
PMID- 25133416
TI - Aerobic Fitness Indices of Children Differed Not by Body Weight Status but by
Level of Engagement in Physical Activity.
AB - BACKGROUND: Moderate-to-vigorous physical activity (MVPA) improves aerobic
fitness in children, which is usually assessed by maximal oxygen consumption.
However, other indices of aerobic fitness have been understudied. OBJECTIVE: To
compare net oxygen (VO2net), net energy consumption (Enet), net mechanical
efficiency (MEnet), and lipid oxidation rate in active and inactive children
across body weight statuses. DESIGN: The sample included normal-weight,
overweight, and obese children of whom 44 are active (>=30 min of MVPA/d) and 41
are inactive (<30 min of MVPA/d). VO2net, Enet, MEnet and lipid oxidation rate
were determined during an incremental maximal cycling test. RESULTS: Active obese
participants had significantly lower values of VO2net and Enet and higher MEnet
than inactive obese participants at all load stages. In addition, active obese
participants showed a significantly higher lipid oxidation rate compared with
inactive obese and active overweight and normal-weight participants. VO2net,
Enet, and MEnet were similar across active children, regardless of body weight
status. CONCLUSIONS: Thirty minutes or more of MVPA per day is associated with a
potentiation of aerobic fitness indicators in obese prepubertal children.
Moreover, the indices of aerobic fitness of inactive obese children are
significantly different from those of active obese and nonobese ones.
PMID- 25133418
TI - IL-1beta inhibition in autoimmune inner ear disease: can you hear me now?
AB - Clinical vignette: A 51-year-old man with right-sided sudden hearing loss
presents to the otology clinic. He has a 4-year history of episodic vertigo of
several hours' duration and fluctuating, progressive sensorineural hearing loss
in his left ear. The vertigo attacks have not occurred for the last 18 months,
and the left ear hearing is consistently poor. The patient's right ear hearing
has dropped in the last 36 hours. MRI imaging of brain and temporal bone are
normal. A 2-week "burst and taper" of oral prednisone is administered with no
effect. Over the next 3 months, serial audiograms show rapidly progressive loss
of threshold and word recognition scores on the right side. A trial of high-dose
prednisone (60 mg/d for 30 days) results in full recovery of the right ear
hearing and substantial improvement in the left ear. As the prednisone dose is
slowly tapered over several months, the hearing drops again.
PMID- 25133419
TI - Too much of a good thing: immunodeficiency due to hyperactive PI3K signaling.
AB - Primary immune deficiency diseases arise due to heritable defects that often
involve signaling molecules required for immune cell function. Typically, these
genetic defects cause loss of gene function, resulting in primary immune
deficiencies such as severe combined immune deficiency (SCID) and X-linked
agammaglobulinemia (XLA); however, gain-of-function mutations may also promote
immune deficiency. In this issue of the JCI, Deau et al. establish that gain-of
function mutations in PIK3R1, which encodes the p85alpha regulatory subunit of
class IA PI3Ks, lead to immunodeficiency. These observations are consistent with
previous reports that hyperactivating mutations in PIK3CD, which encodes the
p110delta catalytic subunit, are capable of promoting immune deficiency.
Mutations that reduce PI3K activity also result in defective lymphocyte
development and function; therefore, these findings support the notion that too
little or too much PI3K activity leads to immunodeficiency.
PMID- 25133417
TI - Providers' perspectives regarding the development of a web-based depression
intervention for Latina/o youth.
AB - Latina/o youth appear to be at significant risk for depression and, of concern,
is the high underutilization of mental health services observed in this
population. There is a tremendous need for novel intervention methods to better
serve the unique needs of this population. This article describes the development
of Rise Above (Siempre Sale el Sol), a Web-based, self-help, depression
intervention for Latina/o adolescents funded by the National Institute of Mental
Health. We applied a cultural adaptation model to an evidence-based depression
treatment to reduce potential service barriers and increase the relevance and
potential efficacy of the intervention for Latina/o youth. We conducted thematic
interviews with 32 national experts to obtain feedback that would inform our
application of the cultural adaptation model, the potential efficacy of the
intervention, and the feasibility of implementation. Future directions for the
evaluation of Rise Above (Siempre Sale el Sol) are described.
PMID- 25133420
TI - Play down protein to play up metabolism?
AB - Who among us hasn't fantasized about a diet that allows ingestion of a surfeit of
calories that are burned off effortlessly by ramping up energy expenditure? In
this issue of the JCI, research led by Christopher Morrison suggests that this
dream may become a reality; however, a complete understanding of the molecular
interface that connects nutrient choices with our cellular metabolism will be
required. Laeger et al. show that the expression and secretion of the weight
reducing hormone fibroblast growth factor 21 (FGF21) is regulated by dietary
proteins and not, as has been heretofore assumed, simply triggered by reduced
caloric intake. This study not only sheds new light on the role of FGF21 in
systems metabolism, but also on the ways our bodies cope with the ever-changing
availability of different dietary macronutrients.
PMID- 25133421
TI - Healing the injured vessel wall using microRNA-facilitated gene delivery.
AB - Drug-eluting stents have emerged as potent weapons in the treatment of patients
with symptomatic coronary artery disease by reducing restenosis rates; however, a
significant clinical consequence of these stents is delayed reendothelialization,
which may increase the risk of late stent thrombosis. In this issue of the JCI,
Santulli and colleagues generated an adenovirus that expresses the cyclin
dependent kinase inhibitor p27(Kip1) (p27) and bears four tandem copies of target
sequences for the endothelial cell-enriched microRNA (miRNA) miR-126-3p (Ad-p27
126TS) in an attempt to specifically reduce proliferation of vascular smooth
muscle cells, but not endothelial cells. Indeed, delivery of Ad-p27-126TS to
balloon-injured arteries in rats not only induced faster and more complete
reendothelialization, but also effectively improved neointimal hyperplasia,
hypercoagulability, and vasoreactivity. Collectively, these findings provide a
cogent foundation for the potential therapeutic use of miRNA-facilitated gene
delivery strategies to heal vessel wall injury.
PMID- 25133422
TI - "RAS"ling beta cells to proliferate for diabetes: why do we need MEN?
AB - Adult human pancreatic beta cells are refractory to current therapeutic
approaches to enhance proliferation. This reluctance to expand is problematic,
especially for people with diabetes who lack sufficient numbers of functional
insulin-producing beta cells and could therefore benefit from therapies for beta
cell expansion. In this issue of the JCI, Chamberlain et al. describe a
surprising series of observations that involve two downstream arms of the RAS
signaling pathway, MAPK and RASSF proteins, which also involve the tumor
suppressor menin. The findings of this study may help explain the difficulty of
inducing beta cell proliferation and may provide leads for therapeutic expansion
of human beta cells.
PMID- 25133423
TI - Inflammatory lymphangiogenesis in postpartum breast tissue remodeling.
AB - Like many cancers, mammary carcinomas use lymphatic vessels to disseminate, and
numerous clinical and experimental studies have documented a strong correlation
between peritumoral lymphangiogenesis and tumor dissemination. At the same time,
many other factors can affect the incidence, invasiveness, and mortality of
breast cancer, including lactation history. Although lactation reduces overall
cancer risk, patients diagnosed within 5 years of pregnancy have an increased
incidence of metastatic disease. In this issue of the JCI, Lyons and colleagues
demonstrate that postpartum breast tissue remodeling during involution coincides
with inflammatory lymphangiogenesis. In mouse models, cyclooxygenase-2 (COX-2)
inhibition during involution reduced the risk of cancer metastasis and correlated
with decreased lymphangiogenesis. In addition to lymphangiogenesis, COX-2
inhibition reduces many of the immune-suppressive features of the tumor
microenvironment, including development of myeloid-derived suppressor cells and
regulatory T cells; therefore, these results support the notion that inhibiting
COX-2 during lactation weaning may lessen the incidence of breast cancer
metastasis.
PMID- 25133424
TI - Menin determines K-RAS proliferative outputs in endocrine cells.
AB - Endocrine cell proliferation fluctuates dramatically in response to signals that
communicate hormone demand. The genetic alterations that override these controls
in endocrine tumors often are not associated with oncogenes common to other tumor
types, suggesting that unique pathways govern endocrine proliferation. Within the
pancreas, for example, activating mutations of the prototypical oncogene KRAS
drive proliferation in all pancreatic ductal adenocarcimomas but are never found
in pancreatic endocrine tumors. Therefore, we asked how cellular context impacts
K-RAS signaling. We found that K-RAS paradoxically suppressed, rather than
promoted, growth in pancreatic endocrine cells. Inhibition of proliferation by K
RAS depended on antiproliferative RAS effector RASSF1A and blockade of the RAS
activated proproliferative RAF/MAPK pathway by tumor suppressor menin. Consistent
with this model, a glucagon-like peptide 1 (GLP1) agonist, which stimulates
ERK1/2 phosphorylation, did not affect endocrine cell proliferation by itself,
but synergistically enhanced proliferation when combined with a menin inhibitor.
In contrast, inhibition of MAPK signaling created a synthetic lethal interaction
in the setting of menin loss. These insights suggest potential strategies both
for regenerating pancreatic beta cells for people with diabetes and for targeting
menin-sensitive endocrine tumors.
PMID- 25133425
TI - Periderm prevents pathological epithelial adhesions during embryogenesis.
AB - Appropriate development of stratified, squamous, keratinizing epithelia, such as
the epidermis and oral epithelia, generates an outer protective permeability
barrier that prevents water loss, entry of toxins, and microbial invasion. During
embryogenesis, the immature ectoderm initially consists of a single layer of
undifferentiated, cuboidal epithelial cells that stratifies to produce an outer
layer of flattened periderm cells of unknown function. Here, we determined that
periderm cells form in a distinct pattern early in embryogenesis, exhibit highly
polarized expression of adhesion complexes, and are shed from the outer surface
of the embryo late in development. Mice carrying loss-of-function mutations in
the genes encoding IFN regulatory factor 6 (IRF6), IkappaB kinase-alpha
(IKKalpha), and stratifin (SFN) exhibit abnormal epidermal development, and we
determined that mutant animals exhibit dysfunctional periderm formation,
resulting in abnormal intracellular adhesions. Furthermore, tissue from a fetus
with cocoon syndrome, a lethal disorder that results from a nonsense mutation in
IKKA, revealed an absence of periderm. Together, these data indicate that
periderm plays a transient but fundamental role during embryogenesis by acting as
a protective barrier that prevents pathological adhesion between immature,
adhesion-competent epithelia. Furthermore, this study suggests that failure of
periderm formation underlies a series of devastating birth defects, including
popliteal pterygium syndrome, cocoon syndrome, and Bartsocas-Papas syndrome.
PMID- 25133426
TI - Cyclooxygenase-2-dependent lymphangiogenesis promotes nodal metastasis of
postpartum breast cancer.
AB - Breast involution following pregnancy has been implicated in the high rates of
metastasis observed in postpartum breast cancers; however, it is not clear how
this remodeling process promotes metastasis. Here, we demonstrate that human
postpartum breast cancers have increased peritumor lymphatic vessel density that
correlates with increased frequency of lymph node metastases. Moreover, lymphatic
vessel density was increased in normal postpartum breast tissue compared with
tissue from nulliparous women. In rodents, mammary lymphangiogenesis was
upregulated during weaning-induced mammary gland involution. Furthermore, breast
cancer cells exposed to the involuting mammary microenvironment acquired
prolymphangiogenic properties that contributed to peritumor lymphatic expansion,
tumor size, invasion, and distant metastases. Finally, in rodent models of
postpartum breast cancer, cyclooxygenase-2 (COX-2) inhibition during the
involution window decreased normal mammary gland lymphangiogenesis, mammary tumor
associated lymphangiogenesis, tumor cell invasion into lymphatics, and
metastasis. Our data indicate that physiologic COX-2-dependent lymphangiogenesis
occurs in the postpartum mammary gland and suggest that tumors within this
mammary microenvironment acquire enhanced prolymphangiogenic activity. Further,
our results suggest that the prolymphangiogenic microenvironment of the
postpartum mammary gland has potential as a target to inhibit metastasis and
suggest that further study of the therapeutic efficacy of COX-2 inhibitors in
postpartum breast cancer is warranted.
PMID- 25133428
TI - A human immunodeficiency caused by mutations in the PIK3R1 gene.
AB - Recently, patient mutations that activate PI3K signaling have been linked to a
primary antibody deficiency. Here, we used whole-exome sequencing and
characterized the molecular defects in 4 patients from 3 unrelated families
diagnosed with hypogammaglobulinemia and recurrent infections. We identified 2
different heterozygous splice site mutations that affect the same splice site in
PIK3R1, which encodes the p85alpha subunit of PI3K. The resulting deletion of
exon 10 produced a shortened p85alpha protein that lacks part of the PI3K p110
binding domain. The hypothetical loss of p85alpha-mediated inhibition of p110
activity was supported by elevated phosphorylation of the known downstream
signaling kinase AKT in patient T cell blasts. Analysis of patient blood revealed
that naive T and memory B cell counts were low, and T cell blasts displayed
enhanced activation-induced cell death, which was corrected by addition of the
PI3Kdelta inhibitor IC87114. Furthermore, B lymphocytes proliferated weakly in
response to activation via the B cell receptor and TLR9, indicating a B cell
defect. The phenotype exhibited by patients carrying the PIK3R1 splice site
mutation is similar to that of patients carrying gain-of-function mutations in
PIK3CD. Our results suggest that PI3K activity is tightly regulated in T and B
lymphocytes and that various defects in the PI3K-triggered pathway can cause
primary immunodeficiencies.
PMID- 25133427
TI - FGF21 is an endocrine signal of protein restriction.
AB - Enhanced fibroblast growth factor 21 (FGF21) production and circulation has been
linked to the metabolic adaptation to starvation. Here, we demonstrated that
hepatic FGF21 expression is induced by dietary protein restriction, but not
energy restriction. Circulating FGF21 was increased 10-fold in mice and rats fed
a low-protein (LP) diet. In these animals, liver Fgf21 expression was increased
within 24 hours of reduced protein intake. In humans, circulating FGF21 levels
increased dramatically following 28 days on a LP diet. LP-induced increases in
FGF21 were associated with increased phosphorylation of eukaryotic initiation
factor 2alpha (eIF2alpha) in the liver, and both baseline and LP-induced serum
FGF21 levels were reduced in mice lacking the eIF2alpha kinase general control
nonderepressible 2 (GCN2). Finally, while protein restriction altered food
intake, energy expenditure, and body weight gain in WT mice, FGF21-deficient
animals did not exhibit these changes in response to a LP diet. These and other
data demonstrate that reduced protein intake underlies the increase in
circulating FGF21 in response to starvation and a ketogenic diet and that FGF21
is required for behavioral and metabolic responses to protein restriction. FGF21
therefore represents an endocrine signal of protein restriction, which acts to
coordinate metabolism and growth during periods of reduced protein intake.
PMID- 25133429
TI - PAX7 expression defines germline stem cells in the adult testis.
AB - Spermatogenesis is a complex, multistep process that maintains male fertility and
is sustained by rare germline stem cells. Spermatogenic progression begins with
spermatogonia, populations of which express distinct markers. The identity of the
spermatogonial stem cell population in the undisturbed testis is controversial
due to a lack of reliable and specific markers. Here we identified the
transcription factor PAX7 as a specific marker of a rare subpopulation of
A(single) spermatogonia in mice. PAX7+ cells were present in the testis at birth.
Compared with the adult testis, PAX7+ cells constituted a much higher percentage
of neonatal germ cells. Lineage tracing in healthy adult mice revealed that PAX7+
spermatogonia self-maintained and produced expanding clones that gave rise to
mature spermatozoa. Interestingly, in mice subjected to chemotherapy and
radiotherapy, both of which damage the vast majority of germ cells and can result
in sterility, PAX7+ spermatogonia selectively survived, and their subsequent
expansion contributed to the recovery of spermatogenesis. Finally, PAX7+
spermatogonia were present in the testes of a diverse set of mammals. Our data
indicate that the PAX7+ subset of A(single) spermatogonia functions as robust
testis stem cells that maintain fertility in normal spermatogenesis in healthy
mice and mediate recovery after severe germline injury, such as occurs after
cancer therapy.
PMID- 25133432
TI - Histologic features mimicking mycosis fungoides induced by imiquimod, 5%: a
potential pitfall for dermatopathologists.
PMID- 25133430
TI - A selective microRNA-based strategy inhibits restenosis while preserving
endothelial function.
AB - Drugs currently approved to coat stents used in percutaneous coronary
interventions do not discriminate between proliferating vascular smooth muscle
cells (VSMCs) and endothelial cells (ECs). This lack of discrimination delays
reendothelialization and vascular healing, increasing the risk of late thrombosis
following angioplasty. We developed a microRNA-based (miRNA-based) approach to
inhibit proliferative VSMCs, thus preventing restenosis, while selectively
promoting reendothelialization and preserving EC function. We used an adenoviral
(Ad) vector that encodes cyclin-dependent kinase inhibitor p27(Kip1) (p27) with
target sequences for EC-specific miR-126-3p at the 3' end (Ad-p27-126TS).
Exogenous p27 overexpression was evaluated in vitro and in a rat arterial balloon
injury model following transduction with Ad-p27-126TS, Ad-p27 (without miR-126
target sequences), or Ad-GFP (control). In vitro, Ad-p27-126TS protected the
ability of ECs to proliferate, migrate, and form networks. At 2 and 4 weeks after
injury, Ad-p27-126TS-treated animals exhibited reduced restenosis, complete
reendothelialization, reduced hypercoagulability, and restoration of the
vasodilatory response to acetylcholine to levels comparable to those in uninjured
vessels. By incorporating miR-126-3p target sequences to leverage endogenous EC
specific miR-126, we overexpressed exogenous p27 in VSMCs, while selectively
inhibiting p27 overexpression in ECs. Our proof-of-principle study demonstrates
the potential of using a miRNA-based strategy as a therapeutic approach to
specifically inhibit vascular restenosis while preserving EC function.
PMID- 25133431
TI - Early efficacy trial of anakinra in corticosteroid-resistant autoimmune inner ear
disease.
AB - BACKGROUND: Autoimmune inner ear disease (AIED) is a rare disease that results in
progressive sensorineural hearing loss. Patients with AIED initially respond to
corticosteroids; however, many patients become unresponsive to this treatment
over time, and there is no effective alternative therapy for these individuals.
METHODS: We performed a phase I/II open-label, single-arm clinical trial of the
IL-1 receptor antagonist anakinra in corticosteroid-resistant AIED patients.
Given that the etiology of corticosteroid resistance is likely heterogeneous, we
used a Simon 2-stage design to distinguish between an unacceptable (<=10%) and an
acceptable (>=30%) response rate to anakinra therapy. Subjects received 100 mg
anakinra by subcutaneous injection for 84 days, followed by a 180-day
observational period. RESULTS: Based on patient responses, the Simon 2-stage rule
permitted premature termination of the trial after 10 subjects completed the 84
day drug period, as the target efficacy for the entire trial had been achieved.
Of these 10 patients, 7 demonstrated audiometric improvement, as assessed by pure
tone average (PTA) and word recognition score (WRS). In these 7 responders,
reduced IL-1beta plasma levels correlated with clinical response. Upon
discontinuation of treatment, 3 subjects relapsed, which correlated with
increased IL-1beta plasma levels. CONCLUSION: We demonstrated that IL-1beta
inhibition in corticosteroid-resistant AIED patients was effective in a small
cohort of patients and that IL-1beta plasma levels associated with both clinical
hearing response and disease relapse. These results suggest that a larger phase
II randomized clinical trial of IL-1beta inhibition is warranted. TRIAL
REGISTRATION: ClinicalTrials.gov NCT01267994. FUNDING: NIH, Merrill & Phoebe
Goodman Otology Research Center, and Long Island Hearing & Speech Society.
PMID- 25133433
TI - Ebola hemorrhagic fever in 2014: the tale of an evolving epidemic.
PMID- 25133434
TI - Patterns of injury, outcomes, and predictors of in-hospital and 1-year mortality
in nonagenarian and centenarian trauma patients.
AB - IMPORTANCE: With the dramatic growth in the very old population and their
concomitant heightened exposure to traumatic injury, the trauma burden among this
patient population is estimated to be exponentially increasing. OBJECTIVE: To
determine the clinical outcomes and predictors of in-hospital and 1-year
mortality in nonagenarian and centenarian trauma patients (NCTPs). DESIGN,
SETTING, AND PARTICIPANTS: All patients 90 years or older admitted to a level 1
academic trauma center between January 1, 2006, and December 31, 2010, with a
primary diagnosis of trauma were included. Standard trauma registry data
variables were supplemented by systematic medical record review. Cumulative
mortality rates at 1, 3, 6, and 12 months after discharge were investigated using
the Social Security Death Index. Univariate and multivariable analyses were
performed to identify the predictors of in-hospital and 1-year postdischarge
cumulative mortalities. MAIN OUTCOMES AND MEASURES: Length of hospital stay, in
hospital mortality, and cumulative mortalities at 1, 3, 6, and 12 months after
discharge. RESULTS: Four hundred seventy-four NCTPs were included; 71.7% were
female, and a fall was the predominant mechanism of injury (96.4%). The mean
patient age was 93 years, the mean Injury Severity Score was 12, and the mean
number of comorbidities per patient was 4.4. The in-hospital mortality was 9.5%
but cumulatively escalated at 1, 3, 6, and 12 months after discharge to 18.5%,
26.4%, 31.3%, and 40.5%, respectively. Independent predictors of in-hospital
mortality were the Injury Severity Score (odds ratio [OR], 1.09; 95% CI, 1.02
1.16; P = .01), mechanical ventilation (OR, 6.23; 95% CI, 1.42-27.27; P = .02),
and cervical spine injury (OR, 4.37; 95% CI, 1.41-13.50; P = .01). Independent
predictors of cumulative 1-year mortality were head injury (OR, 2.65; 95% CI,
1.24-5.67; P = .03) and length of hospital stay (OR, 1.06; 95% CI, 1.02-1.11; P =
.005). Cumulative 1-year mortality in NCTPs with a head injury was 51.1% and
increased to 73.2% if the Injury Severity Score was 25 or higher and to 78.7% if
mechanical ventilation was required. Most NCTPs required rehabilitation; only
8.9% were discharged to home. CONCLUSIONS AND RELEVANCE: Despite low in-hospital
mortality, the cumulative mortality rate among NCTPs at 1 year after discharge is
significant, particularly in the presence of head injury, spine injury,
mechanical ventilation, high injury severity, or prolonged length of hospital
stay. These considerations can help guide clinical decisions and family
discussions.
PMID- 25133435
TI - Breast cancer risk and use of calcium channel blockers using Swedish population
registries.
PMID- 25133439
TI - Demystifying Merkel.
PMID- 25133440
TI - Divine skin.
PMID- 25133441
TI - Solving the mystery of Jimmy's red sweat.
PMID- 25133442
TI - Circulating adiponectin levels and risk of type 2 diabetes in the Japanese.
AB - BACKGROUND: Adiponectin has anti-inflammatory and insulin-sensitizing properties.
Prospective studies have consistently shown a lower risk of type 2 diabetes among
those with higher circulating adiponectin levels. OBJECTIVE: We examined
prospectively the association between serum adiponectin levels and type 2
diabetes risk among Japanese workers, taking visceral fat mass into account.
SUBJECTS AND METHODS: Subjects were 4591 Japanese employees who attended a
comprehensive health screening in 2008; had biochemical data including serum
adiponectin; were free of diabetes at baseline; and received health screening in
2011. Multiple logistic regression analysis was used to examine the association
between adiponectin and incidence of diabetes among overall subjects, as well as
subgroups. Stratified analyses were carried out according to variables including
visceral fat area (VFA). RESULTS: During 3 years of follow-up, 217 diabetic cases
were newly identified. Of these, 87% had a prediabetes at baseline. Serum
adiponectin level was significantly, inversely associated with incidence of
diabetes, with odds ratios (95% confidence interval) adjusted for age, sex,
family history, smoking, alcohol drinking, physical activity and body mass index
(BMI) for the lowest through highest quartile of adiponectin of 1 (reference),
0.79 (0.55-1.12), 0.60 (0.41-0.88) and 0.40 (0.25-0.64), respectively (P-value
for trend <0.01). This association was materially unchanged with adjustment for
VFA instead of BMI. After further adjustment for both homeostasis model
assessment of insulin resistance and hemoglobin A1c, however, the association
became statistically nonsignificant (P-value for trend=0.18). Risk reduction
associated with higher adiponectin levels was observed in both participants with
and without obesity or insulin resistance at baseline. CONCLUSIONS: RESULTS
suggest that higher levels of circulating adiponectin are associated with a lower
risk of type 2 diabetes, independently of overall and intra-abdominal fat
deposition, and that adiponectin may confer a benefit in both persons with and
without insulin resistance.
PMID- 25133449
TI - Low serum 25 hydroxyvitamin D is associated with poor clinicopathologic
characteristics in female patients with papillary thyroid cancer.
AB - BACKGROUND: Vitamin D has recently attracted attention because reduced levels are
associated with the prevalence and aggressiveness of several cancers. This study
aimed to evaluate the relationship between preoperative serum 25 hydroxyvitamin D
(25(OH) vitamin D) levels and clinicopathologic characteristics in female
patients with papillary thyroid cancer (PTC). METHODS: A total of 548 female
patients who underwent total thyroidectomy for PTC between June 2012 and May 2013
were included. Blood samples were obtained within two weeks prior to surgery.
Patients were categorized into four quartiles by preoperative serum 25(OH)
vitamin D levels. The clinicopathologic features of PTC were analyzed
retrospectively. RESULTS: Preoperative 25(OH) vitamin D was significantly lower
in patients with a tumor size of >1 cm (p = 0.041) or lymph node metastasis (LNM;
p = 0.043). No significant trends in several clinicopathologic features were
observed in relation to increasing serum vitamin D concentrations except
decreasing tumor size (p = 0.010). Patients in the second quartile had a greater
occurrence of T stage 3/4 (odds ratio (OR) 2.03 [confidence interval (CI) 1.19
3.44]; p = 0.009), LNM (OR 2.03 [CI 1.19-3.44]; p = 0.009), lateral LNM (OR 5.03
[CI 1.66-15.28]; p = 0.004), and extrathyroidal extension (ETE; OR 1.95 [CI 1.15
3.29]; p = 0.013) than those in the fourth quartile. Multivariate analysis showed
that patients in the second quartile had a greater occurrence of T stage 3/4 (OR
1.89 [CI 1.08-3.30]; p = 0.026), LNM (OR 2.04 [CI 1.20-3.47]; p = 0.009), lateral
LNM (OR 5.12 [CI 1.68-15.59]; p = 0.004), and ETE (OR 1.81 [CI 1.04-3.15]; p =
0.036) than those in the fourth quartile. When the subjects were recategorized
into two groups by median 25(OH) vitamin D levels, those with values below the
median had a significantly higher risk of T stage 3/4, LNM, lateral LNM, stage
III/IV, and ETE. All values except ETE sustained significance after adjustment.
CONCLUSION: Lower preoperative serum 25(OH) vitamin D levels appear to be
associated with poor clinicopathologic features in female patients with PTC.
PMID- 25133451
TI - Decalepisarayalpathra (J. Joseph & V. Chandras.) Venter, an endemic and
endangered ethno medicinal plant from Western Ghats, India.
AB - Decalepis arayalpatra is an endemic and critically endangered plant of India. May
2014 issue of Natural Products Research publishes the findings of R. S. Verma et
al. on the chemical composition of D. arayalpatra. This study was conducted to
characterise the root aroma of this plant for possible industrial applications.
The authors suggest that due to its peculiar vanilla flavour, the plant could be
explored as a potential substitute of vanillin-aroma in the flavour industry.
Owing to the fact that D. arayalpatra is a critically endangered plant species,
and its habitat is now limited to only the protected areas and reserve forest in
southern part of India, and that collecting any plant from such reserve forests
for commercial activities is illegal as per the law of the country, this specific
conclusion of the authors is totally un-substantiated by the law of land, hence,
calls for further review.
PMID- 25133450
TI - Sorghum [Sorghum bicolor (L.) Moench] leaf sheath dye protects against cisplatin
induced hepatotoxicity and oxidative stress in rats.
AB - This study sought to determine the protective effect of dietary inclusion of
sorghum leaf sheath dye on cisplatin-induced hepatotoxicity and oxidative stress
in rats. Adult male rats were randomly divided into four groups with six animals
in each group. Groups I and II were fed a basal diet, while groups III and IV
were fed diets containing 0.5% and 1% sorghum leaf sheath dye, respectively, for
20 days before cisplatin administration. Hepatotoxicity was induced by a single
dose of cisplatin (7 mg/kg body weight, i.p.), and the experiment was terminated
at 3 days after cisplatin injection. The liver and plasma were studied for
hepatotoxicity and antioxidant capacity. Cisplatin caused a significant (P<.05)
alteration in plasma and liver enzymatic (catalase, glutathione-S-transferase
[GST], and superoxide dismutase [SOD]) and nonenzymatic (glutathione [GSH] and
vitamin C) antioxidant indices with a concomitant increase in the malondialdehyde
(MDA) content; however, there was a significant (P<.05) restoration of the
antioxidant status coupled with a significant (P<.05) decrease in the tissue MDA
content, after consumption of diets containing sorghum leaf sheath dye.
Furthermore, dietary inclusion of sorghum leaf sheath dye caused a marked
reduction in the activities of alanine aminotransferase and aspartate
aminotransferase after cisplatin administration. However, the ability of the dye
to prevent significant cisplatin-induced alteration of both plasma and liver
antioxidant indices suggests an antioxidant mechanism of action. Hence, this
protective effect of Sorghum bicolor leaf sheath dye against cisplatin-induced
hepatotoxicity in rats reflects its potential and beneficial role in the
prevention of liver damage associated with cisplatin administration.
PMID- 25133452
TI - Actinomycotic mastoiditis complicated by sigmoid sinus thrombosis and
labyrinthine fistula.
AB - Actinomyces is a rare pathogen that can be the cause of infections in the
digestive and urinary tracts, skin, genitalia, and lungs, which generally have an
indolent clinical course. However, in some cases these can be locally destructive
and become generalized infections. Actinomyces has been previously implicated in
infections of the middle ear, nasopharynx, and sinuses, occasionally causing
complications such as chronic mastoiditis. Here we describe the case of a 10-year
old-male presenting with nausea, vomiting, and headache who developed
intracranial complications of actinomycotic mastoiditis.
PMID- 25133455
TI - Effectiveness of electronic stability control on single-vehicle accidents.
AB - OBJECTIVE: This study aims at evaluating the effectiveness of electronic
stability control (ESC) on single-vehicle injury accidents while controlling for
a number of confounders influencing the accident risk. METHODS: Using police
registered injury accidents from 2004 to 2011 in Denmark with cars manufactured
in the period 1998 to 2011 and the principle of induced exposure, 2 measures of
the effectiveness of ESC were calculated: The crude odds ratio and the adjusted
odds ratio, the latter by means of logistic regression. The logistic regression
controlled for a number of confounding factors, of which the following were
significant. For the driver: Age, gender, driving experience, valid driving
license, and seat belt use. For the vehicle: Year of registration, weight, and
ESC. For the accident surroundings: Visibility, light, and location. Finally, for
the road: Speed limit, surface, and section characteristics. RESULTS: The present
study calculated the crude odds ratio for ESC-equipped cars of getting in a
single-vehicle injury accident as 0.40 (95% confidence interval [CI], 0.34-0.47)
and the adjusted odds ratio as 0.69 (95% CI, 0.54-0.88). No difference was found
in the effectiveness of ESC across the injury severity categories (slight,
severe, and fatal). CONCLUSIONS: In line with previous results, this study
concludes that ESC reduces the risk for single-vehicle injury accidents by 31%
when controlling for various confounding factors related to the driver, the car,
and the accident surroundings. Furthermore, it is concluded that it is important
to control for human factors (at a minimum age and gender) in analyses where
evaluations of this type are performed.
PMID- 25133456
TI - Metadata checklist: identification of CHI3L1 and MASP2 as a biomarker pair for
liver cancer through integrative secretome and transcriptome analysis.
PMID- 25133457
TI - Detection of Salmonella bacterium in drinking water using microring resonator.
AB - A new microring resonator system is proposed for the detection of the Salmonella
bacterium in drinking water, which is made up of SiO2-TiO2 waveguide embedded
inside thin film layer of the flagellin. The change in refractive index due to
the binding of the Salmonella bacterium with flagellin layer causes a shift in
the output signal wavelength and the variation in through and drop port's
intensities, which leads to the detection of Salmonella bacterium in drinking
water. The sensitivity of proposed sensor for detecting of Salmonella bacterium
in water solution is 149 nm/RIU and the limit of detection is 7 * 10(-4)RIU.
PMID- 25133458
TI - Estimated medical cost reductions associated with use of novel oral
anticoagulants vs warfarin in a real-world non-valvular atrial fibrillation
patient population.
AB - OBJECTIVE: RESULTS of randomized clinical trials (RCT) demonstrate that novel
oral anticoagulants (NOAC) are effective therapies for reducing the risk of
stroke in non-valvular atrial fibrillation (NVAF). Prior medical cost avoidance
studies have used warfarin event rates from RCTs, which may differ from patients
receiving treatment in a real-world (RW) setting, where the quality of care may
not be the same as in a RCT. The purpose of this study was to estimate the change
in medical costs related to stroke and major bleeding for each NOAC (apixaban,
dabigatran, and rivoraxaban) relative to warfarin in a RW NVAF population.
METHODS: Patients (n = 23,525) with a diagnosis of NVAF during 2007-2010 were
selected from a Medco population of US health plans. Stroke and major bleeding
excluding intracranial hemorrhage (MBEIH) events were identified using diagnosis
codes on medical claims. RW reference event rates were calculated during periods
of warfarin exposure. RW event rates for NOACs were estimated by multiplying the
corresponding relative risk (RR) from the RCTs by each reference rate. Absolute
risk reductions (ARR) or number of events avoided per patient year were then
estimated. Changes in medical costs associated with each NOAC were calculated by
applying the ARR to the 1-year cost for each event. Costs for stroke and MBEIH
were obtained from the literature. Drug and international normalized ratio
monitoring costs were not considered in this analysis. RESULTS: Compared to RW
warfarin, use of apixaban and dabigatran resulted in total (stroke plus MBEIH)
medical cost reductions of $1245 and $555, respectively, during a patient year.
Rivaroxaban resulted in a medical cost increase of $144. CONCLUSIONS: If relative
risk reductions demonstrated in RCTs persist in a RW setting, apixaban would
confer the greatest medical cost savings vs warfarin, resulting from
significantly lower rates of both stroke and MBEIH.
PMID- 25133459
TI - Minnesota multiphasic personality inventory-2-restructured form (MMPI-2-RF)
predictors of violating probation after felonious crimes.
AB - We compared Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI
2-RF) scores of 25 individuals convicted of felonies who violated probation
within 1 year of sentencing with those of 45 similarly sentenced defendants who
completed probation successfully. The sample (51 males, 19 females) ranged in age
from 18 to 81 years (M = 35.2, SD = 13.8) and had 8 to 16 years of education (M =
11.7, SD = 2.1). The majority were Caucasian (85.7%), but African Americans were
also represented (14.3%). Individuals in the sample were primarily convicted of
mid-level felonies (F-1: 2.9%; F-2: 14.3%; F-3: 22.9%; F-4: 31.4%; F-5: 12.9%).
As hypothesized, moderate to large statistically significant differences between
probation completers and violators were found on several MMPI-2-RF scales,
including Behavioral/Externalizing Dysfunction, Antisocial Behavior, Juvenile
Conduct Problems, Substance Abuse, Aggression, Activation, and Disconstraint.
Relative risk ratio analyses indicated that probationers who produced elevated
scores on these scales were up to 3 times more likely to violate probation than
were those with non-elevated scores. Implications of these results and
limitations of our findings are discussed.
PMID- 25133460
TI - Measurement of math beliefs and their associations with math behaviors in college
students.
AB - Our purpose in the present study was to expand understanding of math beliefs in
college students by developing 3 new psychometrically tested scales as guided by
expectancy-value theory, self-efficacy theory, and health belief model.
Additionally, we identified which math beliefs (and which theory) best explained
variance in math behaviors and performance by college students and which students
were most likely to have problematic math beliefs. Study participants included
368 college math students who completed questionnaires to report math behaviors
(attending class, doing homework, reading textbooks, asking for help) and used a
5-point rating scale to indicate a variety of math beliefs. For a subset of 84
students, math professors provided final math grades. Factor analyses produced a
10-item Math Value Scale with 2 subscales (Class Devaluation, No Future Value), a
7-item single-dimension Math Confidence Scale, and an 11-item Math Barriers Scale
with 2 subscales (Math Anxiety, Discouraging Words). Hierarchical multiple
regression revealed that high levels of the newly discovered class devaluation
belief (guided by expectancy-value theory) were most consistently associated with
poor math behaviors in college students, with high math anxiety (guided by health
belief model) and low math confidence (guided by self-efficacy theory) also found
to be significant. Analyses of covariance revealed that younger and male students
were at increased risk for class devaluation and older students were at increased
risk for poor math confidence.
PMID- 25133461
TI - Examining the validity of the Homework Performance Questionnaire: Multi-informant
assessment in elementary and middle school.
AB - Methods for measuring homework performance have been limited primarily to parent
reports of homework deficits. The Homework Performance Questionnaire (HPQ) was
developed to assess the homework functioning of students in Grades 1 to 8 from
the perspective of both teachers and parents. The purpose of this study was to
examine the factorial validity of teacher and parent versions of this scale, and
to evaluate gender and grade-level differences in factor scores. The HPQ was
administered in 4 states from varying regions of the United States. The
validation sample consisted of students (n = 511) for whom both parent and
teacher ratings were obtained (52% female, mean of 9.5 years of age, 79% non
Hispanic, and 78% White). The cross-validation sample included 1,450 parent
ratings and 166 teacher ratings with similar demographic characteristics. The
results of confirmatory factor analyses demonstrated that the best-fitting model
for teachers was a bifactor solution including a general factor and 2 orthogonal
factors, referring to student self-regulation and competence. The best-fitting
model for parents was also a bifactor solution, including a general factor and 3
orthogonal factors, referring to student self-regulation, student competence, and
teacher support of homework. Gender differences were identified for the general
and self-regulation factors of both versions. Overall, the findings provide
strong support for the HPQ as a multi-informant, multidimensional measure of
homework performance that has utility for the assessment of elementary and middle
school students.
PMID- 25133462
TI - Measuring annual growth using written expression curriculum-based measurement: An
examination of seasonal and gender differences.
AB - The purpose of this study was to examine annual growth patterns and gender
differences in written expression curriculum-based measurement (WE-CBM) when used
in the context of universal screening. Students in second through fifth grade (n
= 672) from 2 elementary schools that used WE-CBM as a universal screener
participated in the study. Student writing samples were scored for production
dependent, production-independent, and accurate-production indicators. Results of
latent growth models indicate that for most WE-CBM outcome indicators across most
grade levels, average growth was curvilinear, with increasing curvilinearity on
all indicators as grade level increased. Evidence of gender differences was mixed
with girls having higher initial scores on all WE-CBM indicators except for total
words written (second and third grades), correct minus incorrect writing
sequences (fourth grade only), and percent correct writing sequences (second
fourth grades) where differences were not statistically significant. Despite
differences in initial level, there were few gender differences in growth and
limited overall between-student variability in linear slope. The results of this
study extend research on annual patterns of growth and gender differences in WE
CBM by analyzing all 3 types of WE-CBM indicators, including upper elementary
grades, and assessing skills more frequently (i.e., 4 to 5 times in 1 year) than
in prior research on annual growth. The findings have implications for universal
screening in WE-CBM and for understanding gender differences in writing
performance.
PMID- 25133463
TI - The role of odors and ultrasonic vocalizations in female rat (Rattus norvegicus)
partner choice.
AB - Intrasexual competition for access to a female mate is believed to be unusual in
wild male rats, which suggests that female choosiness could be more important. It
has been shown that females spend more time with one male than with others when
tested in a multiple partner paradigm. The male of first entry is visited most.
The role of ultrasonic vocalizations (USVs) and male odors in the female rat's
initial choice to approach one male instead of another are studied in these
experiments. In Experiment 1, female rats were allowed to choose between 3
different intact males, whereas in Experiment 2, females could choose between a
devocalized male and 2 intact males. Both experiments started with a 15-min
period with inaccessible males followed by a 15-min period with accessible males
in which the female could copulate with the males of her choice. The results
showed that female rats spent more time with the male of first entry over the
males visited subsequently. No differences were found in USV subtype patterns
emitted by the different males or the time spent sniffing the different males in
the period preceding the choice. In addition, the results of Experiment 2 showed
that females visited the silent males as much as the vocalizing males. Thus, the
present experiments did not offer any evidence suggesting that USVs or individual
differences in male odors play any role in female mate choice. Other factors that
were not investigated in this study might be involved in female rat mate
selection, but it should also be considered that mate selection could be random.
PMID- 25133464
TI - Do primates see the solitaire illusion differently? A comparative assessment of
humans (Homo sapiens), chimpanzees (Pan troglodytes), rhesus monkeys (Macaca
mulatta), and capuchin monkeys (Cebus apella).
AB - An important question in comparative psychology is whether human and nonhuman
animals share similar principles of perceptual organization. Despite much
empirical research, no firm conclusion has been drawn. The Solitaire illusion is
a numerosity illusion in humans that occurs when one misperceives the relative
number of 2 types of items presented in intermingled sets. To date, no study has
investigated whether nonhuman animals perceive the Solitaire illusion as humans
do. Here, we compared the perception of the Solitaire illusion in human and
nonhuman primates in 3 experiments. We first observed (Experiment 1) the
spontaneous behavior of chimpanzees when presented with 2 arrays composed of a
different number of preferred and nonpreferred food items. In probe trials,
preferred items were presented in the Solitaire pattern in 2 different spatial
arrangements (either clustered centrally or distributed on the perimeter).
Chimpanzees did not show any misperception of quantity in the Solitaire pattern.
Next, humans, chimpanzees, rhesus monkeys, and capuchin monkeys underwent the
same testing of relative quantity judgments in a computerized task that also
presented the Solitaire illusion (Experiments 2 and 3). Unlike humans,
chimpanzees did not appear to perceive the illusion, in agreement with Experiment
1. The performance of rhesus monkeys and capuchin monkeys was also different from
that of humans, but was slightly more indicative of a potential Solitaire
illusion. On the whole, our results suggest a potential discontinuity in the
visual mechanisms underlying the Solitaire illusion between human and nonhuman
primates.
PMID- 25133465
TI - Chimpanzees (Pan troglodytes) instrumentally help but do not communicate in a
mutualistic cooperative task.
AB - Chimpanzees cooperate in a variety of contexts, but communicating to influence
and regulate cooperative activities is rare. It is unclear whether this reflects
chimpanzees' general inability or whether they have found other means to
coordinate cooperative activities. In the present study chimpanzees could help a
partner play her role in a mutually beneficial food-retrieval task either by
transferring a needed tool (transfer condition) or by visually or acoustically
communicating the hiding-location of the needed tool (communication condition).
Overall, chimpanzees readily helped their partner by delivering the needed tool,
but none of them communicated the hiding location of the tool to their partner
reliably across trials. These results demonstrate that although chimpanzees can
coordinate their cooperative activities by instrumentally helping their partner
in her role, they do not readily use communication with their partner for this
same end.
PMID- 25133466
TI - Discrimination of holograms and real objects by pigeons (Columba livia) and
humans (Homo sapiens).
AB - The type of stimulus material employed in visual tasks is crucial to all
comparative cognition research that involves object recognition. There is
considerable controversy about the use of 2-dimensional stimuli and the impact
that the lack of the 3rd dimension (i.e., depth) may have on animals' performance
in tests for their visual and cognitive abilities. We report evidence of
discrimination learning using a completely novel type of stimuli, namely,
holograms. Like real objects, holograms provide full 3-dimensional shape
information but they also offer many possibilities for systematically modifying
the appearance of a stimulus. Hence, they provide a promising means for
investigating visual perception and cognition of different species in a
comparative way. We trained pigeons and humans to discriminate either between 2
real objects or between holograms of the same 2 objects, and we subsequently
tested both species for the transfer of discrimination to the other presentation
mode. The lack of any decrements in accuracy suggests that real objects and
holograms were perceived as equivalent in both species and shows the general
appropriateness of holograms as stimuli in visual tasks. A follow-up experiment
involving the presentation of novel views of the training objects and holograms
revealed some interspecies differences in rotational invariance, thereby
confirming and extending the results of previous studies. Taken together, these
results suggest that holograms may not only provide a promising tool for
investigating yet unexplored issues, but their use may also lead to novel
insights into some crucial aspects of comparative visual perception and
categorization.
PMID- 25133467
TI - Partner attractiveness moderates the relationship between number of sexual rivals
and in-pair copulation frequency in humans (Homo sapiens).
AB - Nonhuman males attend to the number of potential sexual rivals in the local
environment to assess sperm competition risk. Males of these species sometimes
perform more frequent in-pair copulations to increase the likelihood of success
in sperm competition. Here, we extend this research to humans, Homo sapiens. We
secured self-report data from 393 men in a committed, sexual, heterosexual
relationship. The results indicate that men whose in-pair partner has more male
coworkers and friends (i.e., potential sexual rivals) also perform more frequent
in-pair copulations, but only among men who perceive their partner to be
particularly attractive relative to assessments of partners by other men in the
sample. This research is the first to empirically investigate the number of
potential male rivals in the local environment as a cue to sperm competition risk
in humans. Discussion addresses limitations of the current research and
highlights directions for future research.
PMID- 25133468
TI - Novel perspectives on arrhythmia-induced cardiomyopathy: pathophysiology,
clinical manifestations and an update on invasive management strategies.
AB - Arrhythmia-induced cardiomyopathy is a partially or completely reversible form of
myocardial dysfunction due to sustained supraventricular and ventricular
arrhythmias. Asynchrony, rapid cardiac rates and rhythm irregularities are the
main factors involved in the development of the disease. The reversible nature of
arrhythmia-induced cardiac dysfunction allows only for a retrospective diagnosis
of the disease once cardiac function is restored following heart rate control. A
high level of suspicion is needed to make a diagnosis at an early stage and
prevent further progression of the disease. Although reversible, arrhythmia
induced cellular and molecular changes may remain, increasing the risk for sudden
death even when normal ejection fraction is restored as well as causing rapid
deterioration of cardiac function and development of heart failure symptoms if
arrhythmia recurs. Appropriate management based on a combination of pharmacologic
and nonpharmacologic strategies to achieve rate control and prevent arrhythmia
recurrence is pivotal to avoid further cardiac function deterioration and to
control symptoms, significantly reducing the risk of heart failure and sudden
cardiac death.
PMID- 25133469
TI - Neoadjuvant chemotherapy and short-term morbidity in patients undergoing
mastectomy with and without breast reconstruction.
AB - IMPORTANCE: Neoadjuvant chemotherapy (NC) is increasingly being used in patients
with breast cancer, and evidence-based reports related to its independent effects
on morbidity after mastectomy with immediate breast reconstruction are limited.
OBJECTIVE: To determine the effect of NC on 30-day postoperative morbidity in
women undergoing mastectomy with or without immediate breast reconstruction.
DESIGN, SETTING, AND PARTICIPANTS: All women undergoing mastectomy with or
without immediate breast reconstruction from January 1, 2005, through December
31, 2011, at university and private hospitals internationally were analyzed using
the American College of Surgeons National Surgical Quality Improvement Program
2005-2011 databases. Patients who received NC were compared with those without a
history of NC to estimate the relative odds of 30-day postoperative overall,
systemic, and surgical site morbidity using model-wise multivariable logistic
regression. EXPOSURE: Neoadjuvant chemotherapy. MAIN OUTCOMES AND MEASURES:
Thirty-day postoperative morbidity (overall, systemic, and surgical site).
RESULTS: Of 85,851 women, 66,593 (77.6%) underwent mastectomy without breast
reconstruction, with 2876 (4.3%) receiving NC; 7893 patients were excluded
because of missing exposure data. The immediate breast reconstruction population
included 19,258 patients (22.4%), with 820 (4.3%) receiving NC. After univariable
analysis, NC was associated with a 20% lower odds of overall morbidity in the
group undergoing mastectomy without breast reconstruction (odds ratio [OR], 0.80;
95% CI, 0.71-0.91) but had no significant effect in the immediate breast
reconstruction group (OR, 0.98; 95% CI, 0.79-1.23). After adjustment for
confounding, NC was independently associated with lower overall morbidity in the
group undergoing mastectomy without breast reconstruction (OR, 0.61; 95% CI, 0.51
0.73) and the immediate tissue expander reconstruction subgroup (OR, 0.49; 95%
CI, 0.30-0.84). Neoadjuvant chemotherapy was associated with decreased odds of
systemic morbidity in 4 different populations: complete sample (OR, 0.59; 95% CI,
0.49-0.71), mastectomy without breast reconstruction (OR, 0.59; 95% CI, 0.48
0.72), any immediate breast reconstruction (OR, 0.57; 95% CI, 0.37-0.88), and the
tissue expander subgroup (OR, 0.41; 95% CI, 0.23-0.72). CONCLUSIONS AND
RELEVANCE: Our study supports the safety of NC in women undergoing mastectomy
with or without immediate breast reconstruction. Neoadjuvant chemotherapy is
associated with lower overall morbidity in the patients undergoing mastectomy
without breast reconstruction and in those undergoing tissue expander breast
reconstruction. In addition, the odds of systemic morbidity were decreased in
patients undergoing mastectomy with and without immediate breast reconstruction.
The mechanisms behind the protective association of NC remain unknown and warrant
further investigation.
PMID- 25133470
TI - The Association Between Exergaming and Physical Activity in Young Adults.
AB - BACKGROUND: Compared with traditional nonactive video games, exergaming
contributes significantly to overall daily physical activity (PA) in experimental
studies, but the association in observational studies is not clear. METHODS: Data
were available in the 2011 to 2012 wave of the Nicotine Dependence in Teens
(NDIT) study (N = 829). Multivariable sex-stratified models assessed the
association between exergaming (1-3 times per month in the past year) and minutes
of moderate and vigorous physical activity in the previous week, and the
association between exergaming and meeting PA recommendations. RESULTS: Compared
with male exergamers, female exergamers were more likely to believe exergames
were a good way to integrate PA into their lives (89% vs 62%, P = .0001). After
we adjusted for covariates, male exergamers were not significantly different from
male nonexergamers in minutes of PA. Female exergamers reported 47 more minutes
of moderate PA in the previous week compared with female nonexergamers (P = .03).
There was no association between exergaming and meeting PA recommendations.
CONCLUSIONS: Exergaming contributes to moderate minutes of PA among women but not
among men. Differences in attitudes toward exergaming should be further explored.
PMID- 25133472
TI - Long-term follow-up of hearing preservation in electric-acoustic stimulation
patients.
AB - BACKGROUND: Hearing preservation (HP) surgery was initiated more than 10 years
ago for combined electric and acoustic stimulation (EAS). Preserved residual low
frequency hearing has been demonstrated to improve speech perception in noise as
well as music appreciation in EAS users up to 2 years. Multiple study groups
aimed to evaluate initial loss of residual hearing (RH) as a consequence of HP
surgery. However, after 1 year and 2 years of follow-up, further decline was
reported. This study aimed to determine RH, speech perception, and the subjective
benefits of EAS 10 years after HP surgery. SUBJECTS AND METHODS: Nine postlingual
EAS partially deaf patients who underwent HP surgery at Antwerp University
Hospital were included in this study (11 implanted ears). Hearing preservation
(0% = loss of hearing; >0%-25% = minimal HP; >25%-75% = partial HP; >75% =
complete HP), speech perception and subjective benefits were evaluated
preoperatively; at 3, 6, 12, 18, and 24 months postoperatively; and annually
thereafter. RESULTS: Complete HP was obtained in three of 11 ears; partial HP in
five of 11 ears; and minimal HP in two of 11 ears, measured during their most
recent follow-up. One subject lost his RH completely across time. The mean rate
of HP was 48% (ranging from 6 months up to 10 years postoperatively). Speech
perception analysis up to 10 years showed a continuous statistically significant
improvement. The maximum subjective benefit was reached 3 months after
implantation and subsequently remained statistically significant unchanged for
the next 10 years. CONCLUSION: Long-term HP in EAS users after HP surgery is
feasible, although a small continuous decline of HP rate of 3% per year was
observed (measured from first fitting up to 6 years postoperative). Nevertheless,
a continuous improvement was found in the speech perception results of the EAS
users across 10 years. Moreover, the positive subjective benefit, assessed 3
months postoperative, remained stable up to 10 years.
PMID- 25133471
TI - Karyotype-specific ear and hearing problems in young adults with Turner syndrome
and the effect of oxandrolone treatment.
AB - OBJECTIVE: To evaluate karyotype-specific ear and hearing problems in young-adult
patients with Turner syndrome (TS) and assess the effects of previous treatment
with oxandrolone (Ox). STUDY DESIGN: Double-blind follow-up study. SETTING:
University hospital. PATIENTS: Sixty-five TS patients (mean age, 24.3 yr)
previously treated with growth hormone combined with placebo, Ox 0.03 mg/kg per
day, or Ox 0.06 mg/kg per day from the age of 8 years and estrogen from the age
of 12 years. INTERVENTION: Ear examination was performed according to standard
clinical practice. Air- and bone conduction thresholds were measured in decibel
hearing level. MAIN OUTCOME MEASURES: We compared patients with total monosomy of
the short arm of the X chromosome (Xp), monosomy 45,X and isochromosome
46,X,i(Xq), with patients with a partial monosomy Xp, mosaicism or other
structural X chromosomal anomalies. We assessed the effect of previous Ox
treatment. RESULTS: Sixty-six percent of the patients had a history of recurrent
otitis media. We found hearing loss in 66% of the ears, including pure
sensorineural hearing loss in 32%. Hearing thresholds in patients with a complete
monosomy Xp were about 10 dB worse compared with those in patients with a partial
monosomy Xp. Air- and bone conduction thresholds were not different between the
placebo and Ox treatment groups. CONCLUSION: Young-adult TS individuals
frequently have structural ear pathology, and many suffer from hearing loss. This
indicates that careful follow-up to detect ear and hearing problems is necessary,
especially for those with a monosomy 45,X or isochromosome 46,X,i(Xq). Ox does
not seem to have an effect on hearing.
PMID- 25133473
TI - Ebola, ethics, and public health: what next?
PMID- 25133474
TI - Rapidly enlarging nodular plaque on the leg.
PMID- 25133475
TI - Gastrointestinal bleeding.
AB - A number of interesting abstracts on gastrointestinal bleeding and endoscopy were
presented at Digestive Disease Week (DDW) this year (3 - 6 May 2014, Chicago,
Illinois). The following abstracts are those that have particular high clinical
importance and the potential for direct impact on the endoscopic care of patients
with gastrointestinal bleeding.
PMID- 25133476
TI - Colonoscopy.
PMID- 25133477
TI - Endoscopic ultrasound.
AB - Endoscopic ultrasound (EUS) continues to present a rich source of innovation,
allowing it to evolve from a diagnostic procedure to a therapeutic modality. This
was obvious from the numerous high-quality presentations at the 2014 Digestive
Disease Week (DDW) held in Chicago, Illinois. This review discusses several of
the presented abstracts of innovations in the field of EUS.
PMID- 25133478
TI - Capsule endoscopy and deep enteroscopy.
AB - During the 2014 Digestive Disease Week in Chicago, many high-quality studies on
small-bowel endoscopy were presented. The most relevant abstracts from around the
world of two complementary procedures - capsule endoscopy and deep enteroscopy -
which have seen rapid changes in recent years, have been selected for this
review.
PMID- 25133479
TI - Endoscopic retrograde cholangiopancreatography.
AB - New technological developments in endoscopic retrograde cholangiopancreatography
(ERCP) for diagnosis and treatment have been slow to progress. However, several
informative study results were presented during the 2014 Digestive Disease Week
(DDW; 3 - 6 May; Chicago, Illinois, USA) in specific ERCP areas, such as
prevention of post-ERCP pancreatitis using nonsteroidal anti-inflammatory drugs
and pancreatic duct stenting. Novel and interesting study results regarding
preoperative stent selection for periampullary tumors, metal stents for hilar
stricture or for prevention of duodenal reflux, and intraductal biliary tumor
ablation using photodynamic therapy or radiofrequency ablation were discussed.
Study results presented at the meeting regarding single-operator cholangioscopy
using the SpyGlass system or direct peroral cholangioscopy have indicated the
possibility of future development. Results using peroral pancreatoscopy and
confocal laser endomicroscopy for biliary lesions, including strictures, were
also presented.
PMID- 25133480
TI - Endoscopy innovations.
AB - Innovation everywhere for everybody - this is the way we can summarize the 2014
Digestive Disease Week, which was held in Chicago, Illinois, last May. Many
sessions introduced new innovative materials and concepts. From the robot of the
future to the simplest ideas, the congress was fertile and sometimes full of
surprises. Abstracts representing significant progress and innovations in the
field of digestive endoscopy are reviewed here.
PMID- 25133481
TI - Esophageal diseases.
PMID- 25133482
TI - Lyn tyrosine kinase regulates androgen receptor expression and activity in
castrate-resistant prostate cancer.
AB - Castrate-resistant prostate cancer (CRPC) progression is a complex process by
which prostate cells acquire the ability to survive and proliferate in the
absence or under very low levels of androgens. Most CRPC tumors continue to
express the androgen receptor (AR) as well as androgen-responsive genes owing to
reactivation of AR. Protein tyrosine kinases have been implicated in supporting
AR activation under castrate conditions. Here we report that Lyn tyrosine kinase
expression is upregulated in CRPC human specimens compared with hormone naive or
normal tissue. Lyn overexpression enhanced AR transcriptional activity both in
vitro and in vivo and accelerated CRPC. Reciprocally, specific targeting of Lyn
resulted in a decrease of AR transcriptional activity in vitro and in vivo and
prolonged time to castration. Mechanistically, we found that targeting Lyn kinase
induces AR dissociation from the molecular chaperone Hsp90, leading to its
ubiquitination and proteasomal degradation. This work indicates a novel mechanism
of regulation of AR stability and transcriptional activity by Lyn and justifies
further investigation of the Lyn tyrosine kinase as a therapeutic target for the
treatment of CRPC.Oncogenesis (2014) 3, e115; doi:10.1038/oncsis.2014.30;
published online 18 August 2014.
PMID- 25133485
TI - The promise of curcumin-phosphatidylcholine complex for cardiometabolic diseases:
more than just 'more curcumin'.
PMID- 25133483
TI - The inhibitor of kappa B kinase-epsilon regulates MMP-3 expression levels and can
promote lung metastasis.
AB - The factors that determine the ability of metastatic tumor cells to expand and
grow in specific secondary site(s) are not yet fully understood. Matrix
metalloproteinases (MMP) were identified as potential regulators of the site
specificity of metastasis. We found that lung carcinoma cells ectopically
expressing high levels of the receptor for the type I insulin like growth factor
receptor (M27(R) cells) had a significant reduction in MMP-3 expression levels
and this coincided with reduced metastasis to the lung. We used these cells to
further investigate signaling pathways regulating MMP-3 expression and the role
that MMP-3 plays in lung metastasis. We show that ectopic IkappaB kinase E (IKKE)
expression in these cells partly restored MMP-3 expression levels and also
sensitized MMP-3 transcription to induction by phorbol 12-myristate 13-acetate
(PMA). This increase in MMP-3 production was due to increased activation of
several signal transduction mediators, including protein kinase C alpha, ERK2,
Akt and the transcription factor p65. Furthermore, reconstitution of MMP-3
expression in M27(R) cells restored their ability to colonize the lung whereas
silencing of MMP-3 in M27 cells reduced metastases. Collectively, our results
implicate IKKE as a central regulator of PMA-induced cell signaling and MMP-3
expression and identify MMP-3 as an enabler of tumor cell expansion in the
lung.Oncogenesis (2014) 3, e116; doi:10.1038/oncsis.2014.28; published online 18
August 2014.
PMID- 25133484
TI - Dual targeting of ErbB-2/ErbB-3 results in enhanced antitumor activity in
preclinical models of pancreatic cancer.
AB - ErbB-3 and its ligand NRG-1beta are key players in driving oncogenic signaling
and resistance to therapy through the activation of the PI3K/Akt pathway. We have
recently reported that EV20, a humanized anti-ErbB3 antibody, possesses a marked
antitumor activity in a variety of human tumor models, including pancreatic
cancer (PC). Here, we report that despite epidermal growth factor receptor
overexpression, PC cells are more sensitive to NRG-1beta than EGF in terms of Akt
activation and cell proliferation. Using stable ErbB-3-knocked down cells and
EV20 in combination with trastuzumab, we showed that dual targeting of ErbB-2 and
ErbB-3 was necessary to completely abrogate ErbB-3 signaling and to impair cell
proliferation. Similarly, enhanced therapeutic efficacy of the antibody
combination was seen in xenografts originating from K-Ras-mutated HPAF-II and
SW1990 cells, without increasing the toxicity. These results indicate that dual
targeting of ErbB-2 and ErbB-3 could represent a new therapeutic approach in
PC.Oncogenesis (2014) 3, e117; doi:10.1038/oncsis.2014.31; published online 18
August 2014.
PMID- 25133486
TI - Prevalence of and attitudes about distracted driving in college students.
AB - OBJECTIVE: To identify current distracted driving (DD) behaviors among college
students, primarily those involving cell phone use, and elucidate the opinions of
the students on the most effective deterrent or intervention for reducing cell
phone use. METHODS: Students enrolled at 12 colleges and universities were
recruited to participate in an online, anonymous survey. Recruitment was done via
school-based list-serves and posters. School sizes ranged from 476 to over
30,000. The validated survey included 38 questions; 17 were specifically related
to distracted driving. RESULTS: Four thousand nine hundred sixty-four
participants completed the surveys; the average age was 21.8, 66% were female,
82.7% were undergraduates, and 47% were white/non-Hispanic. Additionally, 4,517
(91%) reported phoning and/or texting while driving; 4,467 (90%) of drivers said
they talk on the phone while driving; 1,241 (25%) reported using a hands-free
device "most of the time"; 4,467 (90%) of drivers reported texting while driving;
2,488 (50%) reported sending texts while driving on the freeway; 2,978 (60%)
while in stop-and-go traffic or on city streets; and 4,319 (87%) at traffic
lights. Those who drove more often were more likely to drive distracted. When
asked about their capability to drive distracted, 46% said they were capable or
very capable of talking on a cell phone and driving, but they felt that only 8.5%
of other drivers were capable. In a multivariate model, 9 predictors explained
44% of the variance in DD, which was statistically significant, F (17, 4945) =
224.31; P <.0001; R(2) = 0.44. The four strongest predictors (excluding driving
frequency) were self-efficacy (i.e., confidence) in driving while multitasking
(beta = 0.37), perception of safety of multitasking while driving (beta = 0.19),
social norms (i.e., observing others multitasking while driving; beta = 0.29),
and having a history of crashing due to multitasking while driving (beta = 0.11).
CONCLUSIONS: Distracted driving is a highly prevalent behavior among college
students who have higher confidence in their own driving skills and ability to
multitask than they have in other drivers' abilities. Drivers' self-efficacy for
driving and multitasking in the car, coupled with a greater likelihood of having
witnessed DD behaviors in others, greatly increased the probability that a
student would engage in DD. Most students felt that policies, such as laws
impacting driving privilege and insurance rate increases, would influence their
behavior.
PMID- 25133487
TI - Home visit program improves technique survival in peritoneal dialysis.
AB - BACKGROUND: Peritoneal dialysis (PD) is a home therapy, and technique survival is
related to the adherence to PD prescription at home. The presence of a home visit
program could improve PD outcomes. We evaluated its effects on clinical outcome
during 1 year of follow-up. METHODS: This was a case-control study. The case
group included all 96 patients who performed PD in our center on January 1, 2013,
and who attended a home visit program; the control group included all 92 patients
who performed PD on January 1, 2008. The home visit program consisted of several
additional visits to reinforce patients' confidence in PD management in their own
environment. Outcomes were defined as technique failure, peritonitis episode, and
hospitalization. Clinical and dialysis features were evaluated for each patient.
RESULTS: The case group was significantly older (p = 0.048), with a lower grade
of autonomy (p = 0.033), but a better hemoglobin level (p = 0.02) than the
control group. During the observational period, we had 11 episodes of technique
failure. We found a significant reduction in the rate of technique failure in the
case group (p = 0.004). Furthermore, survival analysis showed a significant
extension of PD treatment in the patients supported by the home visit program (52
vs. 48.8 weeks, p = 0.018). We did not find any difference between the two groups
in terms of peritonitis and hospitalization rate; however, trends toward a
reduction of Gram-positive peritonitis rates as well as prevalence and duration
of hospitalization related to PD problems were identified in the case group. The
retrospective nature of the analysis was a limitation of this study. CONCLUSION:
The home visit program improves the survival of PD patients and could reduce the
rate of Gram-positive peritonitis and hospitalization. Video Journal Club
"Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=365168.
PMID- 25133489
TI - Maternal and fetal signs and symptoms associated with uterine rupture in women
with prior cesarean delivery.
AB - Abstract Objective: To describe the association between maternal and fetal
physical signs and symptoms (signs/symptoms) and childbirth outcomes in women
with prior cesarean delivery (CD). Methods: Cases of uterine rupture at a single
institution were reviewed to examine risk factors for experiencing signs/symptoms
and poor childbirth outcomes. Results: Among 21 014 deliveries, 3252 (15.5%) had
prior CD, and 75 (2.3%) had uterine rupture. Of these, 66 (88.0%) labored. Among
those who labored, 51 (77.3%) demonstrated signs/symptoms prior to delivery.
Signs/symptoms included vaginal bleeding, abdominal pain, fetal bradycardia and
decreased fetal heart rate (FHR) variability. Laboring patients with
signs/symptoms were seven times more likely than those without them to have poor
maternal/neonatal outcome (27/51 [52.9%] versus 2/15 [13.3%], OR = 7.31 [95% CI
1.34-52.43], p = 0.0155). In multivariate analysis, risk factors for poor fetal
outcome were cervical ripening (OR 4.99 [95% CI 0.86-28.99, p = 0.0735) and
prolonged FHR deceleration/bradycardia (OR 2.78 [95% CI 0.86-9.10], p = 0.0905).
Fetal tachycardia was a risk factor for poor maternal outcome (OR 8.10 [95% CI
1.40-46.84], p = 0.0195). Conclusions: Among laboring women with uterine rupture,
77% demonstrated maternal or fetal signs/symptoms before delivery. The presence
of at least one sign/symptom identified nearly all laboring patients (27/29
[93.1%]) with poor outcomes.
PMID- 25133488
TI - Hospital performance for pharmacologic venous thromboembolism prophylaxis and
rate of venous thromboembolism : a cohort study.
AB - IMPORTANCE: Hospitalization for acute medical illness is associated with
increased risk of venous thromboembolism (VTE). Although efforts designed to
increase use of pharmacologic VTE prophylaxis are intended to reduce hospital
associated VTE, whether higher rates of prophylaxis reduce VTE in medical
patients is unknown. OBJECTIVE: To examine the association between pharmacologic
VTE prophylaxis rates and hospital-associated VTE. DESIGN, SETTING, AND
PARTICIPANTS: Retrospective, multicenter cohort study conducted at 35 Michigan
hospitals participating in a statewide quality collaborative from January 1,
2011, through September 13, 2012. Trained medical record abstractors at each
hospital collected data from 31 260 general medical patients. Use of VTE
prophylaxis on admission, VTE risk factors, and VTE events 90 days after hospital
admission were recorded using a combination of medical record review and
telephone follow-up. Hospitals were grouped into tertiles of performance based on
rate of pharmacologic prophylaxis use on admission for at-risk patients. MAIN
OUTCOMES AND MEASURES: Association between hospital performance and time to
development of VTE within 90 days of hospital admission. RESULTS: A total of 14
563 of 20 794 patients (70.0%) eligible for pharmacologic prophylaxis received
prophylaxis on admission. The rates of pharmacologic prophylaxis use at hospitals
in the high-, moderate-, and low-performance tertiles were 85.8%, 72.6%, and
55.5%, respectively. A total of 226 VTE events occurred during 1 765 449 days of
patient follow-up. Compared with patients at hospitals in the highest-performance
tertile, the hazard of VTE in patients at hospitals in moderate-performance
(hazard ratio, 1.10; 95% CI, 0.74-1.62) and low-performance (hazard ratio, 0.96,
95% CI, 0.63-1.45) tertiles did not differ after adjusting for potential
confounders. Results remained robust when examining mechanical prophylaxis,
prophylaxis use throughout the hospitalization, and subsequent inpatient stays
after discharge from the index hospitalization. CONCLUSIONS AND RELEVANCE: The
occurrence of 90-day VTE in medical patients after hospitalization is low.
Patients who receive care at hospitals that have lower rates of pharmacologic
prophylaxis do not have higher adjusted hazards of VTE, even after accounting for
individual receipt of pharmacologic prophylaxis. Efforts to increase rates of
pharmacologic VTE prophylaxis in hospitalized medical patients may not
substantively reduce this adverse outcome.
PMID- 25133490
TI - Neurolysis and upper trunk brachial plexus birth palsy. Response.
PMID- 25133492
TI - Effects of a six-month walking intervention on depression in inactive post
menopausal women: a randomized controlled trial.
AB - OBJECTIVES: Physical inactivity and advanced age are associated with risk of
depressive disorders. Physical activity can reduce depressive symptoms in older
subjects with depressive disorders. We investigated whether a walking
intervention program may decrease the occurrence of depressive symptoms in
inactive post-menopausal women without depression. METHOD: A total of 121
participants aged 57-75 years were randomly assigned to a six-month moderate
intensity walking intervention (three times a week, 40 minutes per session,
supervised and home-based) or to a control group (waiting list). Inactivity was
assessed using the Physical Activity Questionnaire for the Elderly. Depression
levels were measured pre- and post-intervention with the Beck depression
inventory (BDI). Several baseline measures were considered as possible predictors
of post-intervention BDI score. RESULTS: Participants in the walking intervention
showed a significant decrease in depression as compared with controls. Baseline
cognitive-BDI subscore, subjective health status, body mass index and adherence
were post-intervention BDI score predictors. CONCLUSION: A six-month, three
session per week, moderate intensity walking intervention with a minimal 50%
adherence rate reduces depression in post-menopausal women at risk for depression
due to physical inactivity. This type of walking intervention could be considered
as a widely accessible prevention strategy to prevent depressive symptoms in post
menopausal women at risk of depression.
PMID- 25133491
TI - Effect of topical tranexamic acid on bleeding and quality of surgical field
during functional endoscopic sinus surgery in patients with chronic
rhinosinusitis: a triple blind randomized clinical trial.
AB - BACKGROUND: The effect of tranexamic acid (TXA) on bleeding and improvement of
surgical field during functional endoscopic sinus surgery (FESS) is not clear
yet. This study was conducted to answer this question. METHODS: This trial was
conducted on 60 patients with chronic sinusitis at Beasat Hospital, Hamadan,
Iran, from April to November 2013. Thirty patients in the intervention group
received three pledgets soaked with TXA 5% and phenylephrine 0.5% for 10 minutes
in each nasal cavity before surgery. Thirty patients in the control group
received phenylephrine 0.5% with the same way. The amount of bleeding and the
quality of surgical field were evaluated at 15, 30, and 45 minutes after the
start of surgery using Boezaart grading. RESULTS: The quality of the surgical
field in the intervention group compared to the control group was significantly
better in the first quarter (P = 0.002) and the second quarter (P = 0.003) but
not in the third quarter (P = 0.163). Furthermore, the amount of bleeding was
much less during all periods in the intervention group than in the control group
(P = 0.001). CONCLUSION: Topical TXA can efficiently reduce bleeding and improve
the surgical field in FESS in patients with rhinosinusitis. Based on these
findings, topical TXA may be a useful method for providing a suitable surgical
field during the first 30 minutes after use. TRIAL REGISTRATION: Iranian Registry
of Clinical Trials IRCT201212139014N15.
PMID- 25133493
TI - Prognosis evaluation in patients with hepatocellular carcinoma after hepatectomy:
comparison of BCLC, TNM and Hangzhou criteria staging systems.
AB - PURPOSE: This study is to evaluate the Hangzhou criteria (HC) for patients with
HCC undergoing surgical resection and to identify whether this staging system is
superior to other staging systems in predicting the survival of resectable HCC.
METHOD: 774 HCC patients underwent surgical resection between 2007 and 2009 in
West China Hospital were enrolled retrospectively. Predictors of survival were
identified using the Kaplan-Meier method and the Cox model. The disease state was
staged by the HC, as well as by the TNM and BCLC staging systems. Prognostic
powers were quantified using a linear trend chi2 test, c-index, and the
likelihood ratio (LHR) chi2 test and correlated using Cox's regression model
adjusted using the Akaike information criterion (AIC). RESULTS: Serum AFP level
(P = 0.02), tumor size (P<0.001), tumor number (P<0.001), portal vein invasion
(P<0.001), hepatic vein invasion (P<0.001), tumor differentiation (P<0.001), and
distant organ (P = 0.016) and lymph node metastasis (P<0.001) were identified as
independent risk factors of survival after resection by multivariate analysis.
The comparison of the different staging system results showed that BCLC had the
best homogeneity (likelihood ratio chi2 test 151.119, P<0.001), the TNM system
had the best monotonicity of gradients (linear trend chi2 test 137.523, P<0.001),
and discriminatory ability was the highest for the BCLC (the AUCs for 1-year
mortality were 0.759) and TNM staging systems (the AUCs for 3-, and 5-year
mortality were 0.738 and 0.731, respectively). However, based on the c-index and
AIC, the HC was the most informative staging system in predicting survival (c
index 0.6866, AIC 5924.4729). CONCLUSIONS: The HC can provide important
prognostic information after surgery. The HC were shown to be a promising
survival predictor in a Chinese cohort of patients with resectable HCC.
PMID- 25133494
TI - Fine-tuning of Smad protein function by poly(ADP-ribose) polymerases and poly(ADP
ribose) glycohydrolase during transforming growth factor beta signaling.
AB - BACKGROUND: Initiation, amplitude, duration and termination of transforming
growth factor beta (TGFbeta) signaling via Smad proteins is regulated by post
translational modifications, including phosphorylation, ubiquitination and
acetylation. We previously reported that ADP-ribosylation of Smads by poly(ADP
ribose) polymerase 1 (PARP-1) negatively influences Smad-mediated transcription.
PARP-1 is known to functionally interact with PARP-2 in the nucleus and the
enzyme poly(ADP-ribose) glycohydrolase (PARG) can remove poly(ADP-ribose) chains
from target proteins. Here we aimed at analyzing possible cooperation between
PARP-1, PARP-2 and PARG in regulation of TGFbeta signaling. METHODS: A robust
cell model of TGFbeta signaling, i.e. human HaCaT keratinocytes, was used.
Endogenous Smad3 ADP-ribosylation and protein complexes between Smads and PARPs
were studied using proximity ligation assays and co-immunoprecipitation assays,
which were complemented by in vitro ADP-ribosylation assays using recombinant
proteins. Real-time RT-PCR analysis of mRNA levels and promoter-reporter assays
provided quantitative analysis of gene expression in response to TGFbeta
stimulation and after genetic perturbations of PARP-1/-2 and PARG based on RNA
interference. RESULTS: TGFbeta signaling rapidly induces nuclear ADP-ribosylation
of Smad3 that coincides with a relative enhancement of nuclear complexes of Smads
with PARP-1 and PARP-2. Inversely, PARG interacts with Smads and can de-ADP
ribosylate Smad3 in vitro. PARP-1 and PARP-2 also form complexes with each other,
and Smads interact and activate auto-ADP-ribosylation of both PARP-1 and PARP-2.
PARP-2, similar to PARP-1, negatively regulates specific TGFbeta target genes
(fibronectin, Smad7) and Smad transcriptional responses, and PARG positively
regulates these genes. Accordingly, inhibition of TGFbeta-mediated transcription
caused by silencing endogenous PARG expression could be relieved after
simultaneous depletion of PARP-1. CONCLUSION: Nuclear Smad function is negatively
regulated by PARP-1 that is assisted by PARP-2 and positively regulated by PARG
during the course of TGFbeta signaling.
PMID- 25133495
TI - Is there a benefit in receiving concurrent chemoradiotherapy for elderly patients
with inoperable thoracic esophageal squamous cell carcinoma?
AB - BACKGROUND AND PURPOSE: The benefit of concurrent chemoradiotherapy (CCRT) in
elderly patients with inoperable esophageal squamous cell carcinoma (SCC) is
controversial. This study aimed to assess the efficiency and safety of CCRT in
elderly thoracic esophageal cancer patients. METHODS AND MATERIALS: Between
January 2002 and December 2011, 128 patients aged 65 years or older treated with
CCRT or radiotherapy (RT) alone for inoperable thoracic esophageal SCC were
analyzed retrospectively (RT alone, n = 55; CCRT, n = 73). RESULTS: No treatment
related deaths occurred and no patients experienced any acute grade 4 non
hematologic toxicities. Patients treated with CCRT developed more severe acute
toxicities than patients who received RT alone. The 3-year overall survival (OS)
rate was 36.1% for CCRT compared with 28.5% following RT alone (p = 0.008).
Multivariate analysis identified T stage and treatment modality as independent
prognostic factors for survival. Further analysis revealed that survival was
significantly better in the CCRT group than in the RT alone group for patients <=
72 years. Nevertheless, the CCRT group had a similar OS to the RT group for
patients > 72 years. CONCLUSION: Our results suggest that elderly patients with
inoperable thoracic esophageal SCC could benefit from CCRT, without major
toxicities. However, for patients older than 72 years, CCRT is not superior to RT
alone in terms of survival benefit.
PMID- 25133496
TI - GPCRsort-responding to the next generation sequencing data challenge: prediction
of G protein-coupled receptor classes using only structural region lengths.
AB - Next generation sequencing (NGS) and the attendant data deluge are increasingly
impacting molecular life sciences research. Chief among the challenges and
opportunities is to enhance our ability to classify molecular target data into
meaningful and cohesive systematic nomenclature. In this vein, the G protein
coupled receptors (GPCRs) are the largest and most divergent receptor family that
plays a crucial role in a host of pathophysiological pathways. For the
pharmaceutical industry, GPCRs are a major drug target and it is estimated that
60%-70% of all medicines in development today target GPCRs. Hence, they require
an efficient and rapid classification to group the members according to their
functions. In addition to NGS and the Big Data challenge we currently face, an
emerging number of orphan GPCRs further demand for novel, rapid, and accurate
classification of the receptors since the current classification tools are
inadequate and slow. This study presents the development of a new classification
tool for GPCRs using the structural features derived from their primary
sequences: GPCRsort. Comparison experiments with the current known GPCR
classification techniques showed that GPCRsort is able to rapidly (in the order
of minutes) classify uncharacterized GPCRs with 97.3% accuracy, whereas the best
available technique's accuracy is 90.7%. GPCRsort is available in the public
domain for postgenomics life scientists engaged in GPCR research with NGS:
http://bioserver.ceng.metu.edu.tr/GPCRSort .
PMID- 25133497
TI - Multi-scales analysis of primate diversity and protected areas at a megadiverse
region.
AB - In this paper, we address the question of what proportion of biodiversity is
represented within protected areas. We assessed the effectiveness of different
protected area types at multiple scales in representing primate biodiversity in
the Brazilian Legal Amazon. We used point locality data and distribution data for
primate species within 1 degrees , 0.5 degrees , and 0.25 degrees spatial
resolution grids, and computed the area of reserves within each cell. Four
different approaches were used - no reserves (A), exclusively strict use reserves
(B), strict and sustainable use reserves (C), and strict and sustainable use
reserves and indigenous lands (D). We used the complementarity concept to select
reserve networks. The proportions of cells that were classified as reserves at a
grid resolution of 1 degrees were 37%, 64%, and 88% for approaches B, C and D,
respectively. Our comparison of these approaches clearly showed the effect of an
increase in area on species representation. Representation was consistently
higher at coarser resolutions, indicating the effect of grain size. The high
number of irreplaceable cells for selected networks identified based on approach
A could be attributed to the use of point locality occurrence data. Although the
limited number of point occurrences for some species may have been due to a
Wallacean shortfall, in some cases it may also be the result of an actual
restricted geographic distribution. The existing reserve system cannot be
ignored, as it has an established structure, legal protection status, and
societal recognition, and undoubtedly represents important elements of
biodiversity. However, we found that strict use reserves (which are exclusively
dedicated to biodiversity conservation) did not effectively represent primate
species. This finding may be related to historical criteria for selecting
reserves based on political, economic, or social motives.
PMID- 25133498
TI - Extracorporeal treatment for acetaminophen poisoning: recommendations from the
EXTRIP workgroup.
AB - BACKGROUND: The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was
created to provide evidence-based recommendations on the use of extracorporeal
treatments (ECTR) in poisoning and the results are presented here for
acetaminophen (APAP). METHODS: After a systematic review of the literature, a
subgroup selected and reviewed the articles and summarized clinical and
toxicokinetic data in order to propose structured voting statements following a
pre-determined format. A two-round modified Delphi method was chosen to reach a
consensus on voting statements, and the RAND/UCLA Appropriateness Method was used
to quantify disagreement. Following discussion, a second vote determined the
final recommendations. RESULTS: Twenty-four articles (1 randomized controlled
trial, 1 observational study, 2 pharmacokinetic studies, and 20 case reports or
case series) were identified, yielding an overall very low quality of evidence
for all recommendations. Clinical data on 135 patients and toxicokinetic data on
54 patients were analyzed. Twenty-three fatalities were reviewed. The workgroup
agreed that N-acetylcysteine (NAC) is the mainstay of treatment, and that ECTR is
not warranted in most cases of APAP poisoning. However, given that APAP is
dialyzable, the workgroup agreed that ECTR is suggested in patients with
excessively large overdoses who display features of mitochondrial dysfunction.
This is reflected by early development of altered mental status and severe
metabolic acidosis prior to the onset of hepatic failure. Specific
recommendations for ECTR include an APAP concentration over 1000 mg/L if NAC is
not administered (1D), signs of mitochondrial dysfunction and an APAP
concentration over 700 mg/L (4630 mmol/L) if NAC is not administered (1D) and
signs of mitochondrial dysfunction and an APAP concentration over 900 mg/L (5960
mmol/L) if NAC is administered (1D). Intermittent hemodialysis (HD) is the
preferred ECTR modality in APAP poisoning (1D). CONCLUSION: APAP is amenable to
extracorporeal removal. Due to the efficacy of NAC, ECTR is reserved for rare
situations when the efficacy of NAC has not been definitively demonstrated.
PMID- 25133500
TI - High throughput micro-well generation of hepatocyte micro-aggregates for tissue
engineering.
AB - The main challenge in hepatic tissue engineering is the fast dedifferentiation of
primary hepatocytes in vitro. One successful approach to maintain hepatocyte
phenotype on the longer term is the cultivation of cells as aggregates. This
paper demonstrates the use of an agarose micro-well chip for the high throughput
generation of hepatocyte aggregates, uniform in size. In our study we observed
that aggregation of hepatocytes had a beneficial effect on the expression of
certain hepatocyte specific markers. Moreover we observed that the beneficial
effect was dependent on the aggregate dimensions, indicating that aggregate
parameters should be carefully considered. In a second part of the study, the
selected aggregates were immobilized by encapsulation in methacrylamide-modified
gelatin. Phenotype evaluations revealed that a stable hepatocyte phenotype could
be maintained during 21 days when encapsulated in the hydrogel. In conclusion we
have demonstrated the beneficial use of micro-well chips for hepatocyte
aggregation and the size-dependent effects on hepatocyte phenotype. We also
pointed out that methacrylamide-modified gelatin is suitable for the
encapsulation of these aggregates.
PMID- 25133501
TI - Sexually transmitted infection related stigma and shame among African American
male youth: implications for testing practices, partner notification, and
treatment.
AB - A self-administered, street intercept survey was conducted in order to examine
the relation of stigma and shame associated with sexually transmitted infections
(STI) to STI testing practices, partner notification, and partner-delivered
treatment among young African American men (n=108) in a low-income, urban
community in San Francisco with high STI burden. Multivariate logistic regression
revealed that increasing STI-related stigma was significantly associated with a
decreased odds of STI testing, such that every standard deviation increase in
stigma score was associated with 0.62 decreased odds of having been tested (aOR:
0.62, 95% CI: 0.38-1.00), controlling for age. STI stigma was also significantly
associated with a decreased willingness to notify non-main partners of an STI
(aOR: 0.64 95% CI: 0.41-0.99). Participants with higher levels of stigma and
shame were also significantly less likely to be willing to deliver STI medication
to a partner (stigma aOR: 0.57, 95% CI: 0.37-0.88; shame aOR 0.53 95% CI: 0.34
0.83). Findings suggest that STI-related stigma and shame, common in this
population, could undermine STI testing, treatment, and partner notification
programs. The medical establishment, one of the institutional factors to have
reinforced this culture of stigma, must aid efforts to reduce its effects through
providing integrated services, reframing sexual health in campaigns, educating
clients, and providing wider options to aid disclosure and partner notification
practices.
PMID- 25133502
TI - Hospital-based program to increase child safety restraint use among birthing
mothers in China.
AB - OBJECTIVE: To evaluate a hospital-based educational program to increase child
safety restraint knowledge and use among birthing mothers. METHODS: A prospective
experimental and control study was performed in the Obstetrics department of
hospitals. A total of 216 new birthing mothers from two hospitals (114 from
intervention hospital and 102 from comparison hospital) were recruited and
enrolled in the study. Intervention mothers received a height chart, an 8-minute
video and a folded pamphlet regarding child safety restraint use during their
hospital stay after giving birth. Evaluation data on the child safety seat (CSS)
awareness, attitudes, and use were collected among both groups before and after
the intervention. An additional phone interview was conducted among the
intervention mothers two months after discharge. RESULTS: No significant
differences existed between groups when comparing demographics. Over 90% of the
intervention mothers found the educational intervention to be helpful to some
extent. A significantly higher percentage of mothers in the intervention than the
comparison group reported that CSS are necessary and are the safest seating
practice. Nearly 20% of the intervention mothers actually purchased CSS for their
babies after the intervention. While in both the intervention and comparison
group, over 80% of mothers identified the ages of two through five as needing
CSS, fewer than 50% of both groups identified infants as needing CSS, even after
the intervention. CONCLUSION: The results indicated that child safety restraint
education implemented in hospitals helps increase birthing mothers' overall
knowledge and use of CSS. Further efforts are needed to address specific age
related needs to promote car seats use among infants.
PMID- 25133503
TI - Copy number variation analysis on a non-Hodgkin lymphoma case-control study
identifies an 11q25 duplication associated with diffuse large B-cell lymphoma.
AB - Recent GWAS have identified several susceptibility loci for NHL. Despite these
successes, much of the heritable variation in NHL risk remains to be explained.
Common copy-number variants are important genomic sources of variability, and
hence a potential source to explain part of this missing heritability. In this
study, we carried out a CNV analysis using GWAS data from 681 NHL cases and 749
controls to explore the relationship between common structural variation and
lymphoma susceptibility. Here we found a novel association with diffuse large B
cell lymphoma (DLBCL) risk involving a partial duplication of the C-terminus
region of the LOC283177 long non-coding RNA that was further confirmed by
quantitative PCR. For chronic lymphocytic leukemia/small lymphocytic lymphoma
(CLL/SLL), known somatic deletions were identified on chromosomes 13q14, 11q22
23, 14q32 and 22q11.22. Our study shows that GWAS data can be used to identify
germline CNVs associated with disease risk for DLBCL and somatic CNVs for
CLL/SLL.
PMID- 25133504
TI - Pyrrolobenzodiazepines (PBDs) do not bind to DNA G-quadruplexes.
AB - The pyrrolo[2,1-c][1,4] benzodiazepines (PBDs) are a family of sequence
selective, minor-groove binding DNA-interactive agents that covalently attach to
guanine residues. A recent publication in this journal (Raju et al, PloS One,
2012, 7, 4, e35920) reported that two PBD molecules were observed to bind with
high affinity to the telomeric quadruplex of Tetrahymena glaucoma based on
Electrospray Ionisation Mass Spectrometry (ESI-MS), Circular Dichroism, UV
Visible and Fluorescence spectroscopy data. This was a surprising result given
the close 3-dimensional shape match between the structure of all PBD molecules
and the minor groove of duplex DNA, and the completely different 3-dimensional
structure of quadruplex DNA. Therefore, we evaluated the interaction of eight PBD
molecules of diverse structure with a range of parallel, antiparallel and mixed
DNA quadruplexes using DNA Thermal Denaturation, Circular Dichroism and Molecular
Dynamics Simulations. Those PBD molecules without large C8-substitutents had an
insignificant affinity for the eight quadruplex types, although those with large
pi-system-containing C8-substituents (as with the compounds evaluated by Raju and
co-workers) were found to interact to some extent. Our molecular dynamics
simulations support the likelihood that molecules of this type, including those
examined by Raju and co-workers, interact with quadruplex DNA through their C8
substituents rather than the PBD moiety itself. It is important for the
literature to be clear on this matter, as the mechanism of action of these agents
will be under close scrutiny in the near future due to the growing number of PBD
based agents entering the clinic as both single-agents and as components of
antibody-drug conjugates (ADCs).
PMID- 25133505
TI - The mutational spectrum of Lynch syndrome in cyprus.
AB - Lynch syndrome is the most common form of hereditary colorectal cancer and is
caused by germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6
and PMS2. Mutation carriers have an increased lifetime risk of developing
colorectal cancer as well as other extracolonic tumours. The aim of the current
study was to evaluate the frequency and distribution of mutations in the MLH1,
MSH2 and MSH6 genes within a cohort of Cypriot families that fulfilled the
revised Bethesda guidelines. The study cohort included 77 patients who fulfilled
at least one of the revised Bethesda guidelines. Mutational analysis revealed the
presence of 4 pathogenic mutations, 3 in the MLH1 gene and 1 in the MSH2 gene, in
5 unrelated individuals. It is noted that out of the 4 pathogenic mutations
detected, one is novel (c.1610delG in exon 14 of the MLH1) and has been detected
for the first time in the Cypriot population. Overall, the pathogenic mutation
detection rate in our patient cohort was 7%. This percentage is relatively low
but could be explained by the fact that the sole criterion for genetic screening
was compliance to the revised Bethesda guidelines. Larger numbers of Lynch
syndrome families and screening of the two additional predisposition genes, PMS2
and EPCAM, are needed in order to decipher the full spectrum of mutations
associated with Lynch syndrome predisposition in Cyprus.
PMID- 25133506
TI - Consideration of sex in clinical trials of transdermal nicotine patch: a
systematic review.
AB - Transdermal nicotine patch (TNP) is 1 of the most commonly used smoking cessation
treatments; however, the efficacy of TNP by sex is not yet clear. The purpose of
the current review was to synthesize how sex has been considered in published
clinical trials of TNP for smoking cessation. The specific aims of the study were
to examine the inclusion of sex in analyses of cessation outcomes, TNP-related
variables (compliance, side effects), and quit-related variables (withdrawal,
cravings); to review the consideration of sex-related variables (menstrual cycle
phase, pregnancy); and to identify needs for future research. Potential articles
published through December 31, 2013 were identified through a MEDLINE search of
the terms "clinical trial," "nicotine patch," and "smoking cessation." Forty-two
studies used all 3 terms and met the inclusion criteria. Approximately half of
the studies reported that they considered sex in smoking cessation outcomes, with
15 studies finding no difference by sex and 7 studies finding better outcomes for
men versus women. Only 5 studies reported data on outcomes by sex in their
publications. No studies reported analysis of TNP compliance or withdrawal by
sex. In the 1 study that examined side effects by sex, more women than men
reported discontinuing TNP because of skin irritation. No study examined the
association of cessation outcomes with menstrual cycle phase. There is a need to
include sex in research on TNP, as well as other pharmacological and behavioral
smoking treatments, to clarify the picture of treatment efficacy for women
compared with men.
PMID- 25133509
TI - MCP/CCR2 signaling is essential for recruitment of mesenchymal progenitor cells
during the early phase of fracture healing.
AB - OBJECTIVE: The purpose of this study was to investigate chemokine profiles and
their functional roles in the early phase of fracture healing in mouse models.
METHODS: The expression profiles of chemokines were examined during fracture
healing in wild-type (WT) mice using a polymerase chain reaction array and
histological staining. The functional effect of monocyte chemotactic protein-1
(MCP-1) on primary mouse bone marrow stromal cells (mBMSCs) was evaluated using
an in vitro migration assay. MCP-1-/- and C-C chemokine receptor 2 (CCR2)-/- mice
were fractured and evaluated by histological staining and micro-computed
tomography (micro-CT). RS102895, an antagonist of CCR2, was continuously
administered in WT mice before or after rib fracture and evaluated by
histological staining and micro-CT. Bone graft exchange models were created in WT
and MCP-1-/- mice and were evaluated by histological staining and micro-CT.
RESULTS: MCP-1 and MCP-3 expression in the early phase of fracture healing were
up-regulated, and high levels of MCP-1 and MCP-3 protein expression observed in
the periosteum and endosteum in the same period. MCP-1, but not MCP-3, increased
migration of mBMSCs in a dose-dependent manner. Fracture healing in MCP-1-/- and
CCR2-/- mice was delayed compared with WT mice on day 21. Administration of
RS102895 in the early, but not in the late phase, caused delayed fracture
healing. Transplantation of WT-derived graft into host MCP-1-/- mice
significantly increased new bone formation in the bone graft exchange models.
Furthermore, marked induction of MCP-1 expression in the periosteum and endosteum
was observed around the WT-derived graft in the host MCP-1-/- mouse. Conversely,
transplantation of MCP-1-/- mouse-derived grafts into host WT mice markedly
decreased new bone formation. CONCLUSIONS: MCP-1/CCR2 signaling in the periosteum
and endosteum is essential for the recruitment of mesenchymal progenitor cells in
the early phase of fracture healing.
PMID- 25133510
TI - Prognostic value of red blood cell distribution width for patients with heart
failure: a systematic review and meta-analysis of cohort studies.
AB - AIMS: Multiple studies have investigated the prognostic role of red blood cell
distribution width (RDW) for patients with heart failure (HF), but the results
have been inconsistent. The aim of the present study was to estimate the impact
of RDW on the prognosis of HF by performing a systematic review and meta
analysis. METHODS AND RESULTS: The Embase, PubMed, and Web of Science databases
were searched up to November 16, 2013 to identify eligible cohort studies. The
quality of each study was assessed using the Newcastle-Ottawa Scale (NOS). The
association between RDW, either on admission or at discharge, and HF outcomes
(all-cause mortality [ACM], heart transplantation, cardiovascular mortality, and
rehospitalization, etc.) were reviewed. The overall hazard ratio (HR) for the
effect of RDW on ACM was pooled using a random-effects model, and the publication
bias was evaluated using funnel plots and Eggers' tests. Seventeen studies, with
a total of 18288 HF patients, were included for systematic review. All eligible
studies indicated that RDW on admission and RDW at discharge, as well as its
change during treatment, were of prognostic significance for HF patients. The HR
for the effect of a 1% increase in baseline RDW on ACM was 1.10 (95% confidence
interval: 1.07-1.13), based on pooling of nine studies that provided related
data. However, publication bias was observed among these studies. CONCLUSIONS: HF
patients with higher RDW may have poorer prognosis than those with lower RDW.
Further studies are needed to explore the potential mechanisms underlying this
association.
PMID- 25133511
TI - Insulin, CCAAT/enhancer-binding proteins and lactate regulate the human 11beta
hydroxysteroid dehydrogenase type 2 gene expression in colon cancer cell lines.
AB - 11beta-Hydroxysteroid dehydrogenases (11beta-HSD) modulate mineralocorticoid
receptor transactivation by glucocorticoids and regulate access to the
glucocorticoid receptor. The isozyme 11beta-HSD2 is selectively expressed in
mineralocorticoid target tissues and its activity is reduced in various disease
states with abnormal sodium retention and hypertension, including the apparent
mineralocorticoid excess. As 50% of patients with essential hypertension are
insulin resistant and hyperinsulinemic, we hypothesized that insulin
downregulates the 11beta-HSD2 activity. In the present study we show that insulin
reduced the 11beta-HSD2 activity in cancer colon cell lines (HCT116, SW620 and HT
29) at the transcriptional level, in a time and dose dependent manner. The
downregulation was reversible and required new protein synthesis. Pathway
analysis using mRNA profiling revealed that insulin treatment modified the
expression of the transcription factor family C/EBPs (CCAAT/enhancer-binding
proteins) but also of glycolysis related enzymes. Western blot and real time PCR
confirmed an upregulation of C/EBP beta isoforms (LAP and LIP) with a more
pronounced increase in the inhibitory isoform LIP. EMSA and reporter gene assays
demonstrated the role of C/EBP beta isoforms in HSD11B2 gene expression
regulation. In addition, secretion of lactate, a byproduct of glycolysis, was
shown to mediate insulin-dependent HSD11B2 downregulation. In summary, we
demonstrate that insulin downregulates HSD11B2 through increased LIP expression
and augmented lactate secretion. Such mechanisms are of interest and potential
significance for sodium reabsorption in the colon.
PMID- 25133512
TI - Multivariable logistic regression model: a novel mathematical model that predicts
visual field sensitivity from macular ganglion cell complex thickness in
glaucoma.
AB - PURPOSE: To design a mathematical model that can predict the relationship between
the ganglion cell complex (GCC) thickness and visual field sensitivity (VFS) in
glaucoma patients. DESIGN: Retrospective cross-sectional case series. METHOD:
Within 3 months from VFS measurements by the Humphrey field analyzer 10-2
program, 83 eyes underwent macular GCC thickness measurements by spectral-domain
optical coherence tomography (SD-OCT). Data were used to construct a multiple
logistic model that depicted the relationship between the explanatory variables
(GCC thickness, age, sex, and spherical equivalent of refractive errors)
determined by a regression analysis and the mean VFS corresponding to the SD-OCT
scanned area. Analyses were performed in half or 8 segmented local areas as well
as in whole scanned areas. A simple logistic model that included GCC thickness as
the single explanatory variable was also constructed. The ability of the logistic
models to depict the real GCC thickness/VFS in SAP distribution was analyzed by
the chi2 test of goodness-of-fit. The significance of the model effect was
analyzed by analysis of variance (ANOVA). RESULTS: Scatter plots between the GCC
thickness and the mean VFS showed sigmoid curves. The chi2 test of goodness-of
fit revealed that the multiple logistic models showed a good fit for the real GCC
thickness/VFS distribution in all areas except the nasal-inferior-outer area.
ANOVA revealed that all of the multiple logistic models significantly predicted
the VFS based on the explanatory variables. Although simple logistic models also
exhibited significant VFS predictability based on the GCC thickness, the model
effect was less than that observed for the multiple logistic models. CONCLUSIONS:
The currently proposed logistic models are useful methods for depicting
relationships between the explanatory variables, including the GCC thickness, and
the mean VFS in glaucoma patients.
PMID- 25133514
TI - "The mask who wasn't there": visual masking effect with the perceptual absence of
the mask.
AB - Does a visual mask need to be perceptually present to disrupt processing? In the
present research, we proposed to explore the link between perceptual and memory
mechanisms by demonstrating that a typical sensory phenomenon (visual masking)
can be replicated at a memory level. Experiment 1 highlighted an interference
effect of a visual mask on the categorization of auditory targets and confirmed
the multimodal nature of knowledge. In Experiment 2, we proposed to reactivate
this mask in a categorization task on visual targets. Results showed that the
sensory mask has disrupted (slower reaction times) the processing of the targets
whether the mask was perceptually present or reactivated in memory. These results
support a sensory-based conception of memory processing and suggest that the
difference between perceptual processes and memory processes is characterized by
the presence (perception) or the absence (memory) of the sensory properties
involved in the activity.
PMID- 25133513
TI - Identification and functional analysis of pheromone and receptor genes in the B3
mating locus of Pleurotus eryngii.
AB - Pleurotus eryngii has recently become a major cultivated mushroom; it uses
tetrapolar heterothallism as a part of its reproductive process. Sexual
development progresses only when the A and B mating types are compatible. Such
mating incompatibility occasionally limits the efficiency of breeding programs in
which crossing within loci-shared strains or backcrossing strategies are
employed. Therefore, understanding the mating system in edible mushroom fungi
will help provide a short cut in the development of new strains. We isolated and
identified pheromone and receptor genes in the B3 locus of P. eryngii and
performed a functional analysis of the genes in the mating process by
transformation. A genomic DNA library was constructed to map the entire mating
type locus. The B3 locus was found to contain four pheromone precursor genes and
four receptor genes. Remarkably, receptor PESTE3.3.1 has just 34 amino acid
residues in its C-terminal cytoplasmic region; therefore, it seems likely to be a
receptor-like gene. Real-time quantitative RT-PCR (real-time qRT-PCR) revealed
that most pheromone and receptor genes showed significantly higher expression in
monokaryotic cells than dikaryotic cells. The pheromone genes PEphb3.1 and
PEphb3.3 and the receptor gene PESTE3.3.1 were transformed into P5 (A3B4). The
transformants were mated with a tester strain (A4B4), and the progeny showed
clamp connections and a normal fruiting body, which indicates the proposed role
of these genes in mating and fruiting processes. This result also confirms that
PESTE3.3.1 is a receptor gene. In this study, we identified pheromone and
receptor genes in the B3 locus of P. eryngii and found that some of those genes
appear to play a role in the mating and fruiting processes. These results might
help elucidate the mechanism of fruiting differentiation and improve breeding
efficiency.
PMID- 25133515
TI - The efficacy of self-paced study in multitrial learning.
AB - In 2 experiments we investigated the efficacy of self-paced study in multitrial
learning. In Experiment 1, native speakers of English studied lists of Dutch
English word pairs under 1 of 4 imposed fixed presentation rate conditions (24 *
1 s, 12 * 2 s, 6 * 4 s, or 3 * 8 s) and a self-paced study condition. Total study
time per list was equated for all conditions. We found that self-paced study
resulted in better recall performance than did most of the fixed presentation
rates, with the exception of the 12 * 2 s condition, which did not differ from
the self-paced condition. Additional correlational analyses suggested that the
allocation of more study time to difficult pairs than to easy pairs might be a
beneficial strategy for self-paced learning. Experiment 2 was designed to test
this hypothesis. In 1 condition, participants studied word pairs in a self-paced
fashion without any restrictions. In the other condition, participants studied
word pairs in a self-paced fashion but total study time per item was equated. The
results showed that allowing self-paced learners to freely allocate study time
over items resulted in better recall performance.
PMID- 25133516
TI - Indanthrone dye revisited after sixty years.
AB - Indanthrone, an old, insoluble dye can be converted into a solution processable,
self-assembling and electroluminescent organic semiconductor, namely
tetraoctyloxydinaptho[2,3-a:2',3'-h]phenazine (P-C8), in a simple one-pot process
consisting of the reduction of the carbonyl group by sodium dithionite followed
by the substitution with solubility inducing groups under phase transfer
catalysis conditions.
PMID- 25133517
TI - Scorpions: a presentation.
AB - Scorpions, at least the species of the family Buthidae whose venoms are better
known, appear as animals that have evolved very little over time. The composition
of their venoms is relatively simple as most toxins have a common structural
motif that is found in other venoms from primitive species. Moreover, all the
scorpion venom toxins principally act on membrane ionic channels of excitable
cells. The results of recent works lead to the conclusion that in scorpions there
is a close relationship between venomous function and innate immune function both
remarkably efficient.
PMID- 25133518
TI - Solid-state NMR analysis of a complex crystalline phase of ronacaleret
hydrochloride.
AB - A crystalline phase of the pharmaceutical compound ronacaleret hydrochloride is
studied by solid-state nuclear magnetic resonance (SSNMR) spectroscopy and single
crystal X-ray diffraction. The crystal structure is determined to contain two
independent cationic molecules and chloride anions in the asymmetric unit, which
combine with the covalent structure of the molecule to yield complex SSNMR
spectra. Experimental approaches based on dipolar correlation, chemical shift
tensor analysis, and quadrupolar interaction analysis are employed to obtain
detailed information about this phase. Density functional theory (DFT)
calculations are used to predict chemical shielding and electric field gradient
(EFG) parameters for comparison with experiment. (1)H SSNMR experiments performed
at 16.4 T using magic-angle spinning (MAS) and homonuclear dipolar decoupling
provide information about hydrogen bonding and molecular connectivity that can be
related to the crystal structure. (19)F and (13)C assignments for the Z' = 2
structure are obtained using DFT calculations, (19)F homonuclear dipolar
correlation, and (13)C-(19)F heteronuclear dipolar correlation experiments.
(35)Cl MAS experiments at 16.4 T observe two chlorine sites that are assigned
using calculated chemical shielding and EFG parameters. SSNMR dipolar correlation
experiments are used to extract (1)H-(13)C, (1)H-(15)N, (1)H-(19)F, (13)C-(19)F,
and (1)H-(35)Cl through-space connectivity information for many positions of
interest. The results allow for the evaluation of the performance of a suite of
SSNMR experiments and computational approaches as applied to a complex but
typical pharmaceutical solid phase.
PMID- 25133519
TI - Effects of Acute Active Video Games on Endothelial Function Following a High-Fat
Meal in Overweight Adolescents.
AB - BACKGROUND: We tested the hypothesis that an active video game following a high
fat meal would partially prevent the unfavorable effect of a high-fat meal on
vascular function in overweight adolescents. METHODS: Twenty-four overweight
adolescents were randomized to either a 60-minute active video game (AVG) group
(n = 12) or seated rest (SR) as a control group (n = 12) after a high-fat meal.
Blood parameters were measured, and vascular function was measured using brachial
artery flow-mediated dilation (FMD) at baseline and 3 hours after a high-fat
meal. RESULTS: No significant interaction was found in any blood parameter. A
high-fat meal significantly increased blood triglyceride and glucose
concentrations in both groups in a similar manner. Brachial artery FMD
significantly decreased in the SR group (13.8 +/- 3.2% to 11.8 +/- 2.5), but
increased in the AVG group (11.4 +/- 4.0% to 13.3 +/- 3.5), with a significant
interaction (P = .034). CONCLUSION: These findings show that an active video game
attenuated high-fat meal-induced endothelial dysfunction. This suggests that an
active video game may have a cardioprotective effect on endothelial function in
overweight adolescents when exposed to a high-fat meal.
PMID- 25133520
TI - Molecular and phytochemical investigation of Angelica dahurica and Angelica
pubescentis essential oils and their biological activity against Aedes aegypti,
Stephanitis pyrioides, and Colletotrichum species.
AB - In this study, Angelica dahurica and Angelica pubescentis root essential oils
were investigated as pest management perspectives, and root samples were also
analyzed genetically using the nuclear ribosomal internal transcribed spacer
(ITS) region as a DNA barcode marker. A. pubescentis root essential oil
demonstrated weak antifungal activity against Colletotrichum acutatum,
Colletotrichum fragariae, and Colletotrichum gloeosporioides, whereas A. dahurica
root essential oil did not show antifungal activity. Conversely, A. dahurica root
essential oil demonstrated better biting deterrent and insecticidal activity
against yellow fever mosquito, Aedes aegypti, and azalea lace bugs, Stephanitis
pyrioides, than A. pubescentis root oil. The major compounds in the A. dahurica
oil were found as alpha-pinene (46.3%), sabinene (9.3%), myrcene (5.5%), 1
dodecanol (5.2%), and terpinen-4-ol (4.9%). alpha-Pinene (37.6%), p-cymene
(11.6%), limonene (8.7%), and cryptone (6.7%) were the major compounds found in
the A. pubescentis oil. In mosquito bioassays, 1-dodecanol and 1-tridecanol
showed antibiting deterrent activity similar to the positive control DEET (N,N
diethyl-3-methylbenzamide) at 25 nmol/cm(2) against Ae. aegypti, whereas only 1
tridecanol showed repellent activity in human-based cloth patch bioassay with
minimum effective dosages (MED) of 0.086 +/- 0.089 mg/cm(2) (DEET = 0.007 +/-
0.003 mg/cm(2)). In larval bioassays, 1-tridecanol was more toxic with an LC50
value of 2.1 ppm than 1-dodecanol having an LC50 value of 5.2 ppm against 1-day
old Ae. aegypti larvae. 1-Dodecanol and 1-tridecanol could be useful for the
natural mosquito control agents.
PMID- 25133521
TI - V-shaped bis-coumarins: synthesis and optical properties.
AB - A highly efficient procedure for the synthesis of bis-coumarins fused at the
pyranone ring has been developed. The electron-rich phenols reacted with esters
of coumarin-3-carboxylic acids, leading to substituted chromeno[3,4-c]chromene
6,7-diones. The reaction is catalyzed by both Lewis acids and 4
dimethylaminopyridine. The most probable mechanistic pathway involves Lewis acid
catalyzed or DMAP catalyzed transesterification, followed by intramolecular
conjugate addition of alpha,beta-unsaturated esters to phenols and subsequent
oxidation of the initially formed intermediate. The reaction is compatible with
various functionalities such as NO2, Br, and OMe. Not only benzene derivatives
but also dihydroxynaphthalenes are reactive in this reaction, and the structure
of the product can be controlled by adjusting the reaction conditions.
Furthermore, a double addition is possible, leading to a horseshoe-shaped system
comprised of seven conjugated rings. Compounds with four structurally unique
skeletons have been obtained and have been shown to strongly absorb in the
violet, blue, and/or green regions of the visible spectrum. Most of them display
strong greenish yellow fluorescence, which can be modulated by both structural
changes and the character of the solvents. Again, introduction of an electron
donating group in the chromeno[3,4-c]chromene-6,7-diones caused a significant red
shift in both the absorption and emission maxima, and the effect became
especially noteworthy in the case of amino substituents.
PMID- 25133523
TI - Nonstoichiometric nucleation and growth of multicomponent nanocrystals in
solution.
AB - The ability to assemble nanoscale functional building blocks is a useful and
modular way for scientists to design valuable materials with specific physical
and chemical properties. Chemists expect multicomponent, heterostructured
nanocrystals to show unique electrical, thermal, and optical properties not seen
in homogeneous, single-phase nanocrystals. Although researchers have made
remarkable advances in heterogeneous nucleation and growth, design of synthetic
conditions for obtaining nanocrystals with a target composition and shape is
still a big challenge. There are several outstanding issues that chemists need to
address before they can successfully carry out the design-based synthesis of
multicomponent nanocrystals. For instance, small changes in the reaction
parameters, such as the precursor, solvent, surfactant, reducing agent, and the
reaction temperature, often result in changes in the structure and chemical
composition of the final product. Although scientists do not fully understand the
mechanisms underlying the nucleation and growth processes involved in the
synthesis of these multicomponent nanocrystals, recent progress in understanding
of the thermodynamic and kinetic factors have improved our control over their
final structure and chemical composition. In this Account, we summarize our
recent advances in understanding of the nucleation and growth mechanisms involved
in the solution-based synthesis of multicomponent nanocrystals. We also discuss
the various challenges encountered in their synthesis, emphasizing what still
needs special consideration. We first discuss the three different nucleation
paths from a thermodynamics perspective: amorphous nucleation, crystalline
nucleation, and two-step nucleation. Amorphous nucleation and two-step nucleation
involve the generation of nonstoichiometric nuclei. We initiate this process
mainly by introducing an imbalance in the concentrations of the reduced elements.
When the nonstoichiometric nuclei grow, we can add secondary elements to the
growing nonstoichiometric nuclei. This leads to either the physical deposition or
atomic mixture formation through the diffusion and rearrangement of constituents.
The processes of mixture formation and the physical deposition of the secondary
constituent element also compete and determine the shape and chemical composition
of the final product. If the free energy change by mixture formation is positive
(DeltaGAB >= 0), physical deposition takes place predominantly, and the spreading
coefficient (S) determines the structure of the nanocrystals. However, when
mixture formation is highly spontaneous (DeltaGAB < -xi), the chemical
composition of the final product is usually stoichiometric, and its shape then
depends on the size of the primary nanocrystals. When the mixture formation and
physical deposition are in competition (-xi <= DeltaGAB < 0), as commonly seen
for many nanoalloy systems, both the chemical composition and the structure are
determined by the size of the primary nanocrystals as well as the degree of
mixture formation at the interface of the constituent components. Finally, we
discuss the challenges and caveats that one needs to take into account when
synthesizing multicomponent nanocrystals.
PMID- 25133524
TI - Team-based surgical care: an important role for academic health centers.
PMID- 25133522
TI - Promises and pitfalls of intracellular delivery of proteins.
AB - The direct delivery of functional proteins into the cell cytosol is a key issue
for protein therapy, with many current strategies resulting in endosomal
entrapment. Protein delivery to the cytosol is challenging due to the high
molecular weight and the polarity of therapeutic proteins. Here we review
strategies for the delivery of proteins into cells, including cell-penetrating
peptides, virus-like particles, supercharged proteins, nanocarriers, polymers,
and nanoparticle-stabilized nanocapsules. The advantages and disadvantages of
these approaches including cytosolar delivery are compared and contrasted, with
promising pathways forward identified.
PMID- 25133525
TI - Surface coating mediated swelling and fracture of silicon nanowires during
lithiation.
AB - Surface passivation of silicon anodes is an appealing design strategy for the
development of reliable, high-capacity lithium-ion batteries. However, the
structural stability of the coating layer and its influence on the lithiation
process remain largely unclear. Herein, we show that surface coating mediates the
swelling dynamics and the fracture pattern during initial lithiation of
crystalline silicon nanopillars. We choose conformally nickel coated silicon
architectures as a model system. Experimental findings are interpreted based on a
chemomechanical model. Markedly different swelling and fracture regimes have been
identified, depending on the coating thickness and silicon nanopillar diameter.
Nanopillars with relatively thin coating display anisotropic swelling similar to
pristine nanopillars, but with different preferred fracture sites. As the coating
thickness increases, the mechanisms become isotropic, with one randomly oriented
longitudinal crack that unzips the core-shell structure. The morphology of
cracked pillars resembles that of a thin-film electrode on a substrate, which is
more amenable to cyclic lithiation without fracture. The knowledge provided here
helps clarify the cycling results of coated nanosilicon electrodes and further
suggests design rules for better performance electrodes through proper control of
the lithiation and fracture.
PMID- 25133526
TI - Systematic genetic analysis identifies Cis-eQTL target genes associated with
glioblastoma patient survival.
AB - Prior expression quantitative trait locus (eQTL) studies have demonstrated
heritable variation determining differences in gene expression. The majority of
eQTL studies were based on cell lines and normal tissues. We performed cis-eQTL
analysis using glioblastoma multiforme (GBM) data sets obtained from The Cancer
Genome Atlas (TCGA) to systematically investigate germline variation's
contribution to tumor gene expression levels. We identified 985 significant cis
eQTL associations (FDR<0.05) mapped to 978 SNP loci and 159 unique genes.
Approximately 57% of these eQTLs have been previously linked to the gene
expression in cell lines and normal tissues; 43% of these share cis associations
known to be associated with functional annotations. About 25% of these cis-eQTL
associations are also common to those identified in Breast Cancer from a recent
study. Further investigation of the relationship between gene expression and
patient clinical information identified 13 eQTL genes whose expression level
significantly correlates with GBM patient survival (p<0.05). Most of these genes
are also differentially expressed in tumor samples and organ-specific controls
(p<0.05). Our results demonstrated a significant relationship of germline
variation with gene expression levels in GBM. The identification of eQTLs-based
expression associated survival might be important to the understanding of genetic
contribution to GBM cancer prognosis.
PMID- 25133527
TI - Characterization of the SUMO-binding activity of the myeloproliferative and
mental retardation (MYM)-type zinc fingers in ZNF261 and ZNF198.
AB - SUMO-binding proteins interact with SUMO modified proteins to mediate a wide
range of functional consequences. Here, we report the identification of a new
SUMO-binding protein, ZNF261. Four human proteins including ZNF261, ZNF198,
ZNF262, and ZNF258 contain a stretch of tandem zinc fingers called
myeloproliferative and mental retardation (MYM)-type zinc fingers. We
demonstrated that MYM-type zinc fingers from ZNF261 and ZNF198 are necessary and
sufficient for SUMO-binding and that individual MYM-type zinc fingers function as
SUMO-interacting motifs (SIMs). Our binding studies revealed that the MYM-type
zinc fingers from ZNF261 and ZNF198 interact with the same surface on SUMO-2
recognized by the archetypal consensus SIM. We also present evidence that MYM
type zinc fingers in ZNF261 contain zinc, but that zinc is not required for SUMO
binding. Immunofluorescence microscopy studies using truncated fragments of
ZNF198 revealed that MYM-type zinc fingers of ZNF198 are necessary for
localization to PML-nuclear bodies (PML-NBs). In summary, our studies have
identified and characterized the SUMO-binding activity of the MYM-type zinc
fingers in ZNF261 and ZNF198.
PMID- 25133528
TI - A method to evaluate genome-wide methylation in archival formalin-fixed, paraffin
embedded ovarian epithelial cells.
AB - BACKGROUND: The use of DNA from archival formalin and paraffin embedded (FFPE)
tissue for genetic and epigenetic analyses may be problematic, since the DNA is
often degraded and only limited amounts may be available. Thus, it is currently
not known whether genome-wide methylation can be reliably assessed in DNA from
archival FFPE tissue. METHODOLOGY/PRINCIPAL FINDINGS: Ovarian tissues, which were
obtained and formalin-fixed and paraffin-embedded in either 1999 or 2011, were
sectioned and stained with hematoxylin-eosin (H&E).Epithelial cells were captured
by laser micro dissection, and their DNA subjected to whole genomic bisulfite
conversion, whole genomic polymerase chain reaction (PCR) amplification, and
purification. Sequencing and software analyses were performed to identify the
extent of genomic methylation. We observed that 31.7% of sequence reads from the
DNA in the 1999 archival FFPE tissue, and 70.6% of the reads from the 2011
sample, could be matched with the genome. Methylation rates of CpG on the Watson
and Crick strands were 32.2% and 45.5%, respectively, in the 1999 sample, and
65.1% and 42.7% in the 2011 sample. CONCLUSIONS/SIGNIFICANCE: We have developed
an efficient method that allows DNA methylation to be assessed in archival FFPE
tissue samples.
PMID- 25133532
TI - MALDI-guided SIMS: multiscale imaging of metabolites in bacterial biofilms.
AB - Mass spectrometry imaging (MSI) is a versatile tool for visualizing molecular
distributions in complex biological specimens, but locating microscopic chemical
features of interest can be challenging in samples that lack a well-defined
anatomy. To address this issue, we developed a correlated imaging approach that
begins with performing matrix-assisted laser desorption/ionization (MALDI) MSI to
obtain low-resolution molecular maps of a sample. The resulting maps are then
used to direct subsequent microscopic secondary ion mass spectrometry (SIMS)
imaging and tandem mass spectrometry (MS/MS) experiments to examine selected
chemical regions of interest. By employing MALDI undersampling, the sample
surface is left mostly unperturbed and available for the SIMS analysis, while
also generating an ablation array that can be used for navigation in SIMS. We
validated this MALDI-guided SIMS approach using cultured biofilms of the
opportunistic pathogen Pseudomonas aeruginosa; bioactive secondary metabolites,
including rhamnolipids and quinolones, were detected and visualized on both macro
and microscopic size scales. MSI mass assignments were confirmed with in situ
MALDI MS/MS and capillary electrophoresis-electrospray ionization MS/MS analysis
of biofilm extracts. Two strains of P. aeruginosa were compared, wild type and a
quorum sensing mutant, and differences in metabolite abundance and distribution
were observed.
PMID- 25133529
TI - Global metabolomic analysis of human saliva and plasma from healthy and diabetic
subjects, with and without periodontal disease.
AB - Recent studies suggest that periodontal disease and type 2 diabetes mellitus are
bi-directionally associated. Identification of a molecular signature for
periodontitis using unbiased metabolic profiling could allow identification of
biomarkers to assist in the diagnosis and monitoring of both diabetes and
periodontal disease. This cross-sectional study identified plasma and salivary
metabolic products associated with periodontitis and/or diabetes in order to
discover biomarkers that may differentiate or demonstrate an interaction of these
diseases. Saliva and plasma samples were analyzed from 161 diabetic and non
diabetic human subjects with a healthy periodontium, gingivitis and
periodontitis. Metabolite profiling was performed using Metabolon's platform
technology. A total of 772 metabolites were found in plasma and 475 in saliva.
Diabetics had significantly higher levels of glucose and alpha-hydroxybutyrate,
the established markers of diabetes, for all periodontal groups of subjects.
Comparison of healthy, gingivitis and periodontitis saliva samples within the non
diabetic group confirmed findings from previous studies that included increased
levels of markers of cellular energetic stress, increased purine degradation and
glutathione metabolism through increased levels of oxidized glutathione and
cysteine-glutathione disulfide, markers of oxidative stress, including increased
purine degradation metabolites (e.g. guanosine and inosine), increased amino acid
levels suggesting protein degradation, and increased omega-3 (docosapentaenoate)
and omega-6 fatty acid (linoleate and arachidonate) signatures. Differences in
saliva between diabetic and non-diabetic cohorts showed altered signatures of
carbohydrate, lipid and oxidative stress exist in the diabetic samples. Global
untargeted metabolic profiling of human saliva in diabetics replicated the
metabolite signature of periodontal disease progression in non-diabetic patients
and revealed unique metabolic signatures associated with periodontal disease in
diabetics. The metabolites identified in this study that discriminated the
periodontal groups may be useful for developing diagnostics and therapeutics
tailored to the diabetic population.
PMID- 25133533
TI - Peripheral arterial disease among adult diabetic patients attending a large
outpatient diabetic clinic at a national referral hospital in Uganda: a
descriptive cross sectional study.
AB - BACKGROUND: Peripheral arterial disease (PAD) is one of the recognised diabetic
macro vascular complications. It is a marker of generalised systemic
atherosclerosis and is closely associated with symptomatic coronary and
cerebrovascular disease, hence significant morbidity and mortality. Among African
adult diabetic populations, screening and diagnosis of PAD is frequently
suboptimal. The aim of this study was to determine the prevalence and associated
clinical factors of PAD in adult ambulatory diabetic patients attending the
outpatient diabetic clinic of Mulago national referral and teaching hospital,
Kampala Uganda. METHODS: In this descriptive cross sectional study, 146
ambulatory adult diabetic patients were studied. Information about their socio
demographic and clinical characteristics, fasting lipid profile status, blood
pressure, glycated haemoglobin (HbA1c) levels and presence of albuminuria was
collected using a pre tested questionnaire. Measurement of ankle brachial index
(ABI) to assess for PAD, defined as a ratio less than 0.9 was performed using a
portable 5-10 MHz Doppler device. Clinical factors associated with PAD were
determined by comparing specific selected characteristics in patients with PAD
and those without. RESULTS: The mean age/standard deviation of the study
participants was 53.9/12.4 years with a male predominance (75, 51.4%). PAD was
prevalent in 57 (39%) study participants. Of these, 34 (59.6%) had symptomatic
PAD. The noted clinical factors associated with PAD in this study population were
presence of symptoms of intermittent claudication and microalbuminuria.
CONCLUSIONS: This study documents a high prevalence of PAD among adult ambulatory
Ugandan diabetic patients. Aggressive screening for PAD using ABI measurement in
adult diabetic patients should be emphasised in Uganda especially in the presence
of symptoms of intermittent claudication and microalbuminuria.
PMID- 25133534
TI - Breast contrast-enhanced ultrasound: is a scoring system feasible? A preliminary
study in China.
AB - OBJECTIVES: Although many studies about breast contrast-enhanced ultrasound had
been conducted, clear diagnostic criteria for evaluating enhancement patterns are
still lacking. This study aims to identify significant indicators for breast
contrast-enhanced ultrasound and to establish an initial scoring system.
MATERIALS AND METHODS: Totally 839 patients were included in the study. This
study was divided into two parts. 364 patients were included in part 1 while 475
in part 2. Conventional ultrasound and contrast-enhanced ultrasound were used to
examine each lesion. Only the cases in part 2 were also examined by elastography.
In part 1, Logistic regression analysis was performed to predict significant
variables. A 5-point scoring system was developed based on the results. In part
2, the scoring system was used to evaluate all the breast lesions. To evaluate
the diagnostic efficacy of the new scoring system, it was compared with the
system established for elastography and conventional ultrasound (BI-RADS).
RESULTS: Three independent variables, namely, lesion scope, margin, and shape
were selected in the final step of the logistic regression analysis in part 1. In
part 2, the area under the ROC (receiver operating characteristic) curve for the
contrast-enhanced scoring system was 0.912. The difference in the diagnostic
capabilities of the contrast-enhanced scoring system and elastography was not
statistically significant (P = 0.17). The difference in the diagnostic
capabilities of the contrast-enhanced scoring system and BI-RADS was
statistically significant (P<0.001). CONCLUSIONS: The contrast-enhanced patterns
of benign and malignant breast tumors are different. The application of a 5-point
scoring system for contrast-enhanced ultrasound is clinically promising.
PMID- 25133537
TI - Venous thromboembolism prophylaxis for medical patients: who needs it?
PMID- 25133535
TI - Habitual functional electrical stimulation therapy improves gait kinematics and
walking performance, but not patient-reported functional outcomes, of people with
multiple sclerosis who present with foot-drop.
AB - BACKGROUND: People with Multiple Sclerosis (pwMS) often experience a disturbed
gait function such as foot-drop. The objective of this pilot study was to
investigate the medium term effects of using Functional Electrical Stimulation
(FES) to treat foot-drop over a period 12 weeks on gait and patient reported
outcomes of pwMS. METHODS AND FINDINGS: Nine pwMS aged 35 to 64 (2 males, 7
females) were assessed on four occasions; four weeks before baseline, at baseline
and after six weeks and twelve weeks of FES use. Joint kinematics and performance
on the 10 meter and 2 minute walk tests (10WT, 2 minWT) were assessed with and
without FES. Participants also completed the MS walking Scale (MSWS), MS impact
scale (MSIS29), Fatigue Severity Score (FSS) and wore an activity monitor for
seven days after each assessment. Compared to unassisted walking, FES resulted in
statistically significant improvements in peak dorsiflexion in swing (p = 0.006),
10MWT (p = 0.006) and 2 minWT (p = 0.002). Effect sizes for the training effect,
defined as the change from unassisted walking at baseline to that at 12 weeks,
indicated improved ankle angle at initial contact (2.6 degrees , 95% CI -1
degrees to 4 degrees , d = 0.78), and a decrease in perceived exertion over the
2 min walking tests (-1.2 points, 95% CI -5.7 to 3.4, d = -0.86). Five
participants exceeded the Minimally Detectable Change (MDC) for a training effect
on the 10mWT, but only two did so for the 2 minWT. No effects of the use of FES
for 12 weeks were found for MSWS, MSIS29, FSS or step count. CONCLUSION: Although
FES to treat foot-drop appears to offer the potential for a medium term training
effect on ankle kinematics and walking speed, this was not reflected in the
patient reported outcomes. This observed lack of relationship between objective
walking performance and patient reported outcomes warrants further investigation.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01977287.
PMID- 25133536
TI - CSF and blood oxytocin concentration changes following intranasal delivery in
macaque.
AB - Oxytocin (OT) in the central nervous system (CNS) influences social cognition and
behavior, making it a candidate for treating clinical disorders such as
schizophrenia and autism. Intranasal administration has been proposed as a
possible route of delivery to the CNS for molecules like OT. While intranasal
administration of OT influences social cognition and behavior, it is not well
established whether this is an effective means for delivering OT to CNS targets.
We administered OT or its vehicle (saline) to 15 primates (Macaca mulatta), using
either intranasal spray or a nebulizer, and measured OT concentration changes in
the cerebral spinal fluid (CSF) and in blood. All subjects received both delivery
methods and both drug conditions. Baseline samples of blood and CSF were taken
immediately before drug administration. Blood was collected every 10 minutes
after administration for 40 minutes and CSF was collected once post-delivery, at
the 40 minutes time point. We found that intranasal administration of exogenous
OT increased concentrations in both CSF and plasma compared to saline. Both
delivery methods resulted in similar elevations of OT concentration in CSF, while
the changes in plasma OT concentration were greater after nasal spray compared to
nebulizer. In conclusion our study provides evidence that both nebulizer and
nasal spray OT administration can elevate CSF OT levels.
PMID- 25133539
TI - Novel mechanisms of sildenafil in pulmonary hypertension involving
cytokines/chemokines, MAP kinases and Akt.
AB - Pulmonary arterial hypertension (PH) is associated with high mortality due to
right ventricular failure and hypoxia, therefore to understand the mechanism by
which pulmonary vascular remodeling initiates these processes is very important.
We used a well-characterized monocrotaline (MCT)-induced rat PH model, and
analyzed lung morphology, expression of cytokines, mitogen-activated protein
kinase (MAPK) phosphorylation, and phosphatidylinositol 3-kinase-Akt (PI-3k-Akt)
pathway and nuclear factor (NF)-kappaB activation in order to elucidate the
mechanisms by which sildenafil's protective effect in PH is exerted. Besides its
protective effect on lung morphology, sildenafil suppressed multiple cytokines
involved in neutrophil and mononuclear cells recruitment including cytokine
induced neutrophil chemoattractant (CINC)-1, CINC-2alpha/beta, tissue inhibitor
of metalloproteinase (TIMP)-1, interleukin (IL)-1alpha, lipopolysaccharide
induced CXC chemokine (LIX), monokine induced by gamma interferon (MIG),
macrophage inflammatory protein (MIP)-1alpha, and MIP-3alpha. NF-kappaB
activation and phosphorylation were also attenuated by sildenafil. Furthermore,
sildenafil reduced extracellular signal-regulated kinase (ERK)1/2 and p38 MAPK
activation while enhanced activation of the cytoprotective Akt pathway in PH.
These data suggest a beneficial effect of sildenafil on inflammatory and kinase
signaling mechanisms that substantially contribute to its protective effects, and
may have potential implications in designing future therapeutic strategies in the
treatment of pulmonary hypertension.
PMID- 25133540
TI - Redox-sensitive induction of Src/PI3-kinase/Akt and MAPKs pathways activate eNOS
in response to EPA:DHA 6:1.
AB - AIMS: Omega-3 fatty acid products containing eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA) have vasoprotective effects, in part, by stimulating
the endothelial formation of nitric oxide (NO). This study determined the role of
the EPA:DHA ratio and amount, and characterized the mechanism leading to
endothelial NO synthase (eNOS) activation. METHODS AND RESULTS: EPA:DHA 6?1 and
9?1 caused significantly greater endothelium-dependent relaxations in porcine
coronary artery rings than EPA:DHA 3?1, 1?1, 1?3, 1?6, 1?9, EPA and DHA alone,
and EPA:DHA 6?1 with a reduced EPA + DHA amount, which were inhibited by an eNOS
inhibitor. Relaxations to EPA:DHA 6?1 were insensitive to cyclooxygenase
inhibition, and reduced by inhibitors of either oxidative stress, Src kinase, PI3
kinase, p38 MAPK, MEK, or JNK. EPA:DHA 6?1 induced phosphorylation of Src, Akt,
p38 MAPK, ERK, JNK and eNOS; these effects were inhibited by MnTMPyP. EPA:DHA 6?1
induced the endothelial formation of ROS in coronary artery sections as assessed
by dihydroethidium, and of superoxide anions and hydrogen peroxide in cultured
endothelial cells as assessed by electron spin resonance with the spin probe CMH,
and the Amplex Red based assay, respectively. CONCLUSION: Omega-3 fatty acids
cause endothelium-dependent NO-mediated relaxations in coronary artery rings,
which are dependent on the EPA:DHA ratio and amount, and involve an intracellular
activation of the redox-sensitive PI3-kinase/Akt and MAPKs pathways to activate
eNOS.
PMID- 25133541
TI - Osteopontin is expressed in the mouse uterus during early pregnancy and promotes
mouse blastocyst attachment and invasion in vitro.
AB - Embryo implantation into the maternal uterus is a decisive step for successful
mammalian pregnancy. Osteopontin (OPN) is a member of the small integrin-binding
ligand N-linked glycoprotein family and participates in cell adhesion and
invasion. In this study, we showed that Opn mRNA levels are up-regulated in the
mouse uterus on day 4 and at the implantation sites on days 5 and 8 of pregnancy.
Immunohistochemistry localized the OPN protein to the glandular epithelium on day
4 and to the decidual zone on day 8 of pregnancy. OPN mRNA and proteins are
induced by in vivo and in vitro decidualization. OPN expression in the
endometrial stromal cells is regulated by progesterone, a key regulator during
decidualization. As a secreted protein, the protein level of OPN in the uterine
cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN
can facilitate blastocyst hatching and adhesion. Knockdown of OPN attenuates the
adhesion and invasion of blastocysts in mouse endometrial stromal cells by
suppressing the expression and enzymatic activity of matrix metalloproteinase-9
in the trophoblast. Our data indicated that OPN expression in the mouse uterus
during early pregnancy is essential for blastocyst hatching and adhesion and that
the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained
in vitro trophoblast invasion.
PMID- 25133542
TI - Coptidis rhizome and Si Jun Zi Tang can prevent Salmonella enterica serovar
Typhimurium infection in mice.
AB - Salmonella, a common zoonotic pathogen, causes gastroenteritis in both humans and
animals. Traditional Chinese Medicine (TCM) has been used to improve
gastrointestinal dysfunction and to modify the immune response to inflammation
for centuries. This study used six herbal plants and four TCM formulae to rate
their efficacy in preventing S. Typhimurium infection via mouse model. Minimum
bactericidal concentration (MBC) of Coptidis rhizome (CR) against the reference
strain tallied 12.5 mg/ml and against clinical isolate ST21 was 25 mg/ml. MBCs of
other herbal extracts and formulae on Salmonella Typhimurium strains were above
50 mg/ml. In the mice model, CR and Si Jun Zi Tang (SJZT) could significantly
decrease the bacterial load in organs and blood after being challenged, along
with body weight loss due to the infection. CR and SJZT alleviated infection
induced interferon-gamma levels in the serum and tissues, and tumor necrosis
factor-alpha (TNF-alpha) levels in intestinal tissues. CR and SJZT serum
metabolites could suppress S. Typhimurium invasion and TNF-alpha expression in
RAW264.7 cells. The therapeutic activity of CR and SJZT may involve berberine,
ginsenoside Rb1, and glycyrrhizin, interfering with Salmonella when invading
macrophages. CR and SJZT has shown potential in preventing S. Typhimurium
infection through the regulation of the immune response.
PMID- 25133543
TI - The global trade in fresh produce and the vagility of plant viruses: a case study
in garlic.
AB - As cuisine becomes globalized, large volumes of fresh produce are traded
internationally. The potential exists for pathogens infecting fresh produce to
hitchhike to new locations and perhaps to establish there. It is difficult to
identify them using traditional methods if pathogens are novel, scarce, and/or
unexpected. In an attempt to overcome this limitation, we used high-throughput
sequencing technology as a means of detecting all RNA viruses infecting garlic
(Allium sativum L.) bulbs imported into Australia from China, the USA, Mexico,
Argentina and Spain, and those growing in Australia. Bulbs tested were grown over
multiple vegetative generations and all were stably infected with one or more
viruses, including two species not previously recorded in Australia. Present in
various combinations from 10 garlic bulbs were 41 virus isolates representing
potyviruses (Onion yellow dwarf virus, Leek yellow stripe virus), carlaviruses
(Shallot latent virus, Garlic common latent virus) and allexiviruses (Garlic
virus A, B, C, D, and X), for which 19 complete and 22 partial genome sequences
were obtained, including the first complete genome sequences of two isolates of
GarVD. The most genetically distinct isolates of GarVA and GarVX described so far
were identified from Mexico and Argentina, and possible scenarios explaining this
are presented. The complete genome sequence of an isolate of the potexvirus
Asparagus virus 3 (AV3) was obtained in Australia from wild garlic (A. vineale
L.), a naturalized weed. This is first time AV3 has been identified from wild
garlic and the first time it has been identified beyond China and Japan. The need
for routine generic diagnosis and appropriate legislation to address the risks to
primary production and wild plant communities from pathogens spread through the
international trade in fresh produce is discussed.
PMID- 25133544
TI - Are articulatory settings mechanically advantageous for speech motor control?
AB - We address the hypothesis that postures adopted during grammatical pauses in
speech production are more "mechanically advantageous" than absolute rest
positions for facilitating efficient postural motor control of vocal tract
articulators. We quantify vocal tract posture corresponding to inter-speech
pauses, absolute rest intervals as well as vowel and consonant intervals using
automated analysis of video captured with real-time magnetic resonance imaging
during production of read and spontaneous speech by 5 healthy speakers of
American English. We then use locally-weighted linear regression to estimate the
articulatory forward map from low-level articulator variables to high-level
task/goal variables for these postures. We quantify the overall magnitude of the
first derivative of the forward map as a measure of mechanical advantage. We find
that postures assumed during grammatical pauses in speech as well as speech-ready
postures are significantly more mechanically advantageous than postures assumed
during absolute rest. Further, these postures represent empirical extremes of
mechanical advantage, between which lie the postures assumed during various
vowels and consonants. Relative mechanical advantage of different postures might
be an important physical constraint influencing planning and control of speech
production.
PMID- 25133545
TI - Decontamination of adsorbed chemical warfare agents on activated carbon using
hydrogen peroxide solutions.
AB - Mild treatment with hydrogen peroxide solutions (3-30%) efficiently decomposes
adsorbed chemical warfare agents (CWAs) on microporous activated carbons used in
protective garments and air filters. Better than 95% decomposition of adsorbed
sulfur mustard (HD), sarin, and VX was achieved at ambient temperatures within 1
24 h, depending on the H2O2 concentration. HD was oxidized to the nontoxic HD
sulfoxide. The nerve agents were perhydrolyzed to the respective nontoxic
methylphosphonic acids. The relative rapidity of the oxidation and perhydrolysis
under these conditions is attributed to the microenvironment of the micropores.
Apparently, the reactions are favored due to basic sites on the carbon surface.
Our findings suggest a potential environmentally friendly route for
decontamination of adsorbed CWAs, using H2O2 without the need of cosolvents or
activators.
PMID- 25133547
TI - Towards full citizenship: correlates of engagement with the gender identity law
among transwomen in Argentina.
AB - INTRODUCTION: In May 2012, Argentina passed its "Gender Identity" Law, which
aimed to address the legal invisibility, discrimination and marginalization that
transgender individuals have historically faced. The aim of this study was to
explore factors associated with engagement with the Gender Identity Law among
transwomen living in Argentina. METHODS: Data were derived from a 2013
nationwide, cross-sectional study involving transwomen in Argentina. Using
multivariate logistic regression, we assessed the prevalence and factors
associated with acquiring a gender-congruent identity card within the first 18
months of enactment of the Gender Identity Law. RESULTS: Among 452 transwomen,
260 (57.5%) reported that they had obtained a new gender-congruent identity card.
In multivariate analysis, factors positively associated with acquiring a new ID
were: previously experiencing discrimination by healthcare workers (adjusted odd
ratio [aOR] = 2.01, 95% CI: 1.27-3.20); having engaged in transition procedures
(aOR = 3.06, 95% CI: 1.58-5.93); and having a job other than sex work (aOR =
1.81, 95% CI: 1.06-3.10). Foreign born transwomen were less likely to have
obtained a new ID (aOR = 0.14, 95% CI: 0.06-0.33). CONCLUSIONS: More than half of
transwomen in our sample acquired a new gender-congruent ID within the first 18
months of enactment of the Gender Identity Law. However, access to and uptake of
this right has been heterogeneous. In particular, our findings suggest that the
most empowered transwomen may have been among the first to take advantage of this
right. Although educational level, housing conditions, HIV status and sex work
were not associated with the outcome, foreign-born status was a strong negative
correlate of new ID acquisition. Therefore, additional efforts should be made in
order to ensure that benefits of this founding policy reach all transwomen in
Argentina.
PMID- 25133548
TI - Determinants of patients' choice of provider in accessing brucellosis care among
pastoral communities adjacent to lake Mburo National Park in Kiruhura District,
Uganda.
AB - BACKGROUND: Brucellosis is the commonest zoonotic infection worldwide with
symptoms similar to other febrile syndromes such as malaria and typhoid fever. It
is often easily misdiagnosed, resulting in underreporting and misdirected
treatments. Understanding of the factors that influence brucellosis care seeking
is essential in enhancing its effective management. Our study sought to determine
the factors associated with choice of provider in accessing care for brucellosis
among pastoral communities in Uganda. METHODS: This was a cross-sectional survey
involving 245 randomly selected respondents previously diagnosed and treated for
brucellosis, two months before the study. They were enrolled from three sub
counties neighboring Lake Mburo National Park between December 2012 to April
2013. Data on socio-demographics, availability, accessibility, affordability and
acceptability of health services were collected. A multivariable logistic
regression model was fitted to determine association between independent and
outcome variables using odds ratios and 95% confidence intervals with p
value<=0.05 considered statistically significant. RESULTS: Of the 245
respondents, 127(51.8%) sought health care at government facilities and the rest
at private. Respondents who were less likely to choose a government facility were
either single (OR: 0.50, CI: 0.26-0.97), had general weakness (OR: 0.09, CI: 0.01
0.72) or whom family took a decision (OR: 0.52, CI: 0.28-0.97). At multivariable
analysis, choice of government facility was influenced by primary education (aOR:
0.46, CI: 0.22-0.97), having six to ten household members (aOR:3.71, CI:1.84
7.49), family advice (aOR:0.64, CI: 0.23-0.91), distance >=10 kms (aOR:0.44, CI:
0.21-0.92), high costs at private clinics (aOR:0.01, CI:0.02-0.15) and no
diagnosis at government facility (aOR:0.11, CI:0.01-0.97). Females were more
likely to seek health care at government facilities, while those with tertiary
education were less likely, after the first provider. CONCLUSIONS: Females and
households with six to ten members were more likely to choose government
facilities. Government facilities need to be equipped to attract more patients.
PMID- 25133546
TI - Evaluation of uric acid as a prognostic blood-based marker in a large cohort of
pancreatic cancer patients.
AB - BACKGROUND: Recently, chemical blood parameters gain more attraction as potential
prognostic parameters in pancreatic cancer (PC). In the present study we
investigated the prognostic relevance of the uric acid (UA) level in blood plasma
at the time of diagnosis for overall survival (OS) in a large cohort of patients
with PC. PATIENTS AND METHODS: Data from 466 consecutive patients with ductal
adenocarcinoma of the pancreas were evaluated retrospectively. Overall survival
(OS) was analysed using the Kaplan-Meier method. To further evaluate the
prognostic significance of the UA level, univariate and multivariate Cox
regression models were calculated. RESULTS: None of the clinicopathological
parameters (tumour grade, clinical stage, age, CA19-9 level, Karnofski Index (KI)
or surgical resection) except gender was associated with UA level. In univariate
analysis we observed the elevated UA level (<5.1 versus >=5.1 mg/dl, p = 0.017)
as poor prognostic factor for OS. In the multivariate analysis that included age,
gender, tumour grade, tumour stage, surgical resection, CA19-9 level, the KI and
UA level we confirmed the UA level as independent prognostic factor for OS (HR =
1.373%; CI = 1.077-1.751; p = 0.011). CONCLUSION: In conclusion, we identified
the UA level at time of diagnosis as an independent prognostic factor in PC
patients. Our results indicate that the UA level might represent a novel and
useful marker for patient stratification in PC management.
PMID- 25133549
TI - Cross-checking different sources of mobility information.
AB - The pervasive use of new mobile devices has allowed a better characterization in
space and time of human concentrations and mobility in general. Besides its
theoretical interest, describing mobility is of great importance for a number of
practical applications ranging from the forecast of disease spreading to the
design of new spaces in urban environments. While classical data sources, such as
surveys or census, have a limited level of geographical resolution (e.g.,
districts, municipalities, counties are typically used) or are restricted to
generic workdays or weekends, the data coming from mobile devices can be
precisely located both in time and space. Most previous works have used a single
data source to study human mobility patterns. Here we perform instead a cross
check analysis by comparing results obtained with data collected from three
different sources: Twitter, census, and cell phones. The analysis is focused on
the urban areas of Barcelona and Madrid, for which data of the three types is
available. We assess the correlation between the datasets on different aspects:
the spatial distribution of people concentration, the temporal evolution of
people density, and the mobility patterns of individuals. Our results show that
the three data sources are providing comparable information. Even though the
representativeness of Twitter geolocated data is lower than that of mobile phone
and census data, the correlations between the population density profiles and
mobility patterns detected by the three datasets are close to one in a grid with
cells of 2*2 and 1*1 square kilometers. This level of correlation supports the
feasibility of interchanging the three data sources at the spatio-temporal scales
considered.
PMID- 25133551
TI - Topical prescription contrition.
PMID- 25133552
TI - Monodisperse colloidal gallium nanoparticles: synthesis, low temperature
crystallization, surface plasmon resonance and Li-ion storage.
AB - We report a facile colloidal synthesis of gallium (Ga) nanoparticles with the
mean size tunable in the range of 12-46 nm and with excellent size distribution
as small as 7-8%. When stored under ambient conditions, Ga nanoparticles remain
stable for months due to the formation of native and passivating Ga-oxide layer
(2-3 nm). The mechanism of Ga nanoparticles formation is elucidated using nuclear
magnetic resonance spectroscopy and with molecular dynamics simulations. Size
dependent crystallization and melting of Ga nanoparticles in the temperature
range of 98-298 K are studied with X-ray powder diffraction, specific heat
measurements, transmission electron microscopy, and X-ray absorption
spectroscopy. The results point to delta (delta)-Ga polymorph as a single low
temperature phase, while phase transition is characterized by the large
hysteresis and by the large undercooling of crystallization and melting points
down to 140-145 and 240-250 K, respectively. We have observed size-tunable
plasmon resonance in the ultraviolet and visible spectral regions. We also report
stable operation of Ga nanoparticles as anode material for Li-ion batteries with
storage capacities of 600 mAh g(-1), 50% higher than those achieved for bulk Ga
under identical testing conditions.
PMID- 25133553
TI - Mimosa (Mimosa caesalpiniifolia) prevents oxidative DNA damage induced by cadmium
exposure in Wistar rats.
AB - The Mimosa (Mimosa caesalpiniifolia) is a plant native from South America; it is
used in the traditional medicine systems for treating bacterial, fungal,
parasitic and inflammatory conditions. The aim of this study was to evaluate the
antigenotoxic and antioxidant activities induced by mimosa (M. caesalpiniifolia)
in multiple rodent organs subjected to intoxication with cadmium chloride. A
total of 40 Wistar rats (8 weeks old, 250 g) were distributed into eight groups
(n = 5), as follows: Control group (non-treated group, CTRL); Cadmium exposed
group (Cd); cadmium exposure and treated with extract at 62.5 mg/kg/day; cadmium
exposure and treated with extract at 125 mg/kg/day; cadmium exposure and treated
with extract at 250 mg/kg/day; cadmium exposure and treated with ethyl acetate
fraction at 62.5 mg/kg/day. For evaluating the toxicogenetic potential of mimosa,
two groups were included in the study being treated with extract at 250 mg/kg/day
and acetate fraction of mimosa at 62 mg/kg/day, only. Extract of mimosa at
concentrations of 62.5 and 125 mg decreased DNA damage in animals intoxicated
with cadmium when compared to cadmium group. In a similar manner, treatment with
ethyl acetate fraction of mimosa at 62.5 mg concentration in animals previously
exposed to cadmium reduced genetic damage in peripheral blood cells. In a similar
manner, the treatment with ethyl acetate fraction reduced DNA damage in liver
cells. Oxidative DNA damage was reduced to animals exposed to cadmium and treated
with 125 mg of extract as well as those intoxicated to cadmium and treated with
62.5 of acetate fraction of mimosa. Taken together, our results indicate that
mimosa prevents genotoxicity induced by cadmium exposure in liver and peripheral
blood cells of rats as a result of antioxidant activity.
PMID- 25133554
TI - May maternal anti-mullerian hormone levels predict adverse maternal and perinatal
outcomes in preeclampsia?
AB - BACKGROUND: Prediction of preeclampsia and adverse maternal and perinatal
outcomes with biomarkers has been proposed previously. Anti-mullerian hormone
(AMH) is a growth factor, which is primarily responsible of the regression of the
mullerian duct, but also used to predict ovarian reserve and decreases with age
similar to the fertility. AIM: To evaluate the predictive role of maternal anti
mullerian hormone (mAMH) in adverse maternal and perinatal outcomes in
preeclampsia. METHODS: This prospective case-control study was conducted at
current high-risk pregnancy department in a tertiary research hospital and 45
cases with preeclampsia classified as study group and 42 as control group. Data
collected and evaluated were; age, body mass index (BMI), marriage duration (MD),
gestational weeks (GW), gravidity, parity, mode of delivery, birth weight,
newborn Apgar score, newborn gender, maternal complication, perinatal outcome,
some laboratory parameters and mAMH. The association between mAMH levels and
maternal and fetal outcomes were evaluated. RESULTS: There were no statistically
significant differences between groups in terms of age, BMI, MD, gravidity,
parity and newborn gender (p > 0.05). GW, vaginal delivery, birth weight, newborn
Apgar score, were statistically significantly lower in preeclamptic patients when
compared with non-preeclamptic patients (p < 0.001). Adverse maternal and
perinatal outcomes were statistically significantly higher in the study group (p
< 0.001). The laboratory values [alanine transaminase (ALT), aspartate
transaminase (AST), blood urea nitrogen (BUN), creatinine, lactic dehydrogenase
(LDH), uric acid and fibrinogen) were statistically significantly lower in the
control group (p < 0.001). The mAMH level was significantly lower in the
preeclamptic group (p: 0.035). There was no correlation between mAMH levels and
demographic and clinical parameters. The area under the ROC curve (AUC) was 0.590
and the cut-off value was 0.365 ng/ml with sensitivity of 67.4% and specificity
of 47.1% for mAMH. Logistic regression analysis showed a statistically
insignificance between mAMH and maternal complication and perinatal outcome (p:
0.149). CONCLUSION: According to this study, mAMH level was lower in preeclamptic
patients than in normal pregnants, and is found to be a discriminative factor
with low sensitivity and specificity. There was no relationship between mAMH and
adverse maternal and perinatal outcomes. Further randomized controlled studies
with more participants are needed to evaluate the accurate effects of mAMH levels
on preeclampsia and should increase the power of mAMH levels in predicting the
preeclampsia.
PMID- 25133555
TI - [Interesting cases in IOL implantation].
PMID- 25133556
TI - [Recurrent anterior chamber and vitreous bleeding after cataract surgery].
PMID- 25133550
TI - Tandem RNA chimeras contribute to transcriptome diversity in human population and
are associated with intronic genetic variants.
AB - Chimeric RNAs originating from two or more different genes are known to exist not
only in cancer, but also in normal tissues, where they can play a role in human
evolution. However, the exact mechanism of their formation is unknown. Here, we
use RNA sequencing data from 462 healthy individuals representing 5 human
populations to systematically identify and in depth characterize 81 RNA tandem
chimeric transcripts, 13 of which are novel. We observe that 6 out of these 81
chimeras have been regarded as cancer-specific. Moreover, we show that a
prevalence of long introns at the fusion breakpoint is associated with the
chimeric transcripts formation. We also find that tandem RNA chimeras have lower
abundances as compared to their partner genes. Finally, by combining our results
with genomic data from the same individuals we uncover intronic genetic variants
associated with the chimeric RNA formation. Taken together our findings provide
an important insight into the chimeric transcripts formation and open new avenues
of research into the role of intronic genetic variants in post-transcriptional
processing events.
PMID- 25133557
TI - [Refractive lens exchange with a multifocal lens: well operated, but still
dissatisfied].
PMID- 25133558
TI - [Phakic intraocular lens implantation in the case of a large white-to-white
distance].
PMID- 25133559
TI - [Alterations of intraocular pressure in comparison of self- and external
administered topical antiglaucomatosa during diurnal intraocular pressure
measurements].
AB - BACKGROUND: The correct self-administration of topical antiglaucomatous eye drops
is important for the success of glaucoma treatment. Individual impairment, like
increased age, decreased visual acuity, impaired visual-field perception or the
frequency of drug appliance may influence a correct application technique and the
patients compliance and therewith intraocular pressure (IOP). The aim of this
study was to explore alterations of IOP due to self versus external
administration (by trained medical personnel) of topical antiglaucomatous eye
drops due to impairing factors. MATERIAL AND METHODS: A prospective analysis was
undertaken of 123 patients with primary chronic open-angle glaucoma receiving a
diurnal intraocular pressure (DIP) measurement over 72 hours at our department.
During the first 24 hours, the application of topical eye drops was self
administered by patients (SA), while the application of eye drops within the
following 48 hours was performed by trained medical personnel (EA). Alterations
of mean intraocular pressure (MIP) and diurnal fluctuations (DF) between EA and
SA were analysed with regard to initial IOP, restrictions of visual field
perception, visual acuity, age, general health status and frequency of daily eye
drop administration. RESULTS: Overall comparable MIP in SA and EA was seen. 19.2
43.9 % of the patients with an initial IOP >= 11 mmHg showed beneficial effects
of EA with lowering of IOP under 15.5 mmHg. 27.6 % of the patients showed
lowering of DF < 5 mmHg due to EA. EA influenced DF beneficially in cases of poor
visual acuity (<= 0.1, - 0.8 mmHg) and frequent drop administration (- 0.75
mmHg). CONCLUSIONS: Subpopulations of investigated patients showed lowering of
MIP due to EA, although EA showed no MIP lowering effects in comparison with SA
in general. Glaucoma-impaired patients show decreased DF by EA. Particularly
beneficial influences to DF by EA were observed due to impaired visual acuity and
frequent drop administration. We recommend a 72-hour DIP to evaluate individual
parameters influencing the success of topical glaucomatous treatment. The benefit
of EA in patients with certain impairments should be the subject of further
investigations.
PMID- 25133561
TI - [Treatment of primary open angle glaucoma in a case of multiple chemical
sensitivity syndrome: a case report].
PMID- 25133560
TI - [The relationship between the temperature increase caused by phacoemulsification
and the damage to the corneal endothelium].
AB - PURPOSE: Endothelial cell damage can be found after a phacoemulsification. The
reason for this cell damage is not yet known. The temperature rise inside the
anterior chamber during the emulsification of the lens is considered as a
potential damage mechanism. The aim of this study was to investigate the
relationship between the temperature increase and the cell damage. MATERIALS AND
METHODS: This study was performed with 86 enucleated porcine eyes, which were
divided into six groups A-F. Group A served as control group. Phacoemulsification
was simulated in the groups B-E with different surgically relevant system
settings. The temperature change was measured simultaneously with temperature
sensors inside the anterior chamber. Inside the eyes of group F, the instruments
were positioned and irrigation and aspiration were activated, but no ultrasound
was applied. For all 86 corneas, the endothelial cell damage was quantified with
a standardised evaluation protocol using scanning electron microscopy (SEM). A
potential correlation was checked between the observed cell damage and the
measured temperature rise. RESULTS: The highest temperature increase in group E
with an obstructed aspiration line and an output power setting of 50 % was 17.77
degrees C. The temperature increase in group D with an output power setting of
100 % and unblocked fluid flow was significantly lower (p = 0.006). The highest
temperature increase in group D was 8.89 degrees C. In contrast, the cells in
group D were rated with a significantly lower score value than the cells in group
E (p < 0.001). No significant correlation between the temperature rise and the
cell damage could be obtained in due consideration of all measured data. However,
an increase of the output power setting was connected with a non-linear increase
of the cell loss. CONCLUSION: The temperature rise was not the main reason for
the endothelial cell damage in the performed experiments. Therefore, there seems
to be no causal relationship between the temperature increase inside the anterior
chamber during a common phacoemulsification and the endothelial cell damage. Due
to the strong dependence between the output power setting and the cell damage,
the lowest output power setting should be used during surgery which ensures the
emulsification of the nucleus.
PMID- 25133562
TI - [Objective refraction - retinoscopy].
PMID- 25133564
TI - The rationale for use of Ulipristal Acetate as first line in emergency
contraception: biological and clinical evidence.
AB - Ulipristal acetate (UPA) was licensed as an emergency contraceptive (EC) in
Europe in 2009. By the end of May 2013, over 1.4 million courses had been used.
The rationale for using UPA for EC in favor of the much more commonly used
levonorgestrel (LNG) is based on data on efficacy, safety and side effects.
EFFICACY: In two large clinical trials among women presenting for EC up to 120
hours after unprotected sex, UPA was as effective as LNG at preventing pregnancy.
When the two trials were combined in a meta analysis UPA was superior, almost
halving the risk of pregnancy compared with LNG. Biomedical studies have shown
that UPA inhibits or delays ovulation more effectively than LNG at a stage of the
cycle when the risk of pregnancy is highest. Safety and side effects: UPA and LNG
have similar side effect profiles and to date no serious adverse events have been
attributed to use of UPA for EC. Data on pregnancies conceived in association
with UPA use are reassuring. There is no evidence for teratogenesis or for any
increased risk of ectopic pregnancy or miscarriage. AVAILABILITY: Use of UPA will
remain limited until it is available without a doctor's prescription.
PMID- 25133565
TI - Using skype to conduct interviews for psychosocial research.
PMID- 25133566
TI - Developing guidelines for mentorship.
PMID- 25133573
TI - Correlation of [RuCl3(dppb)(VPy)] cytotoxicity with its effects on the cell
membranes: an investigation using Langmuir monolayers as membrane models.
AB - One of the major challenges in drug design is to identify compounds with
potential toxicity toward target cells, preferably with molecular-level
understanding of their mode of action. In this study, the antitumor property of a
ruthenium complex, mer-[RuCl3(dppb)(VPy)] (dppb = 1,4
bis(diphenylphosphine)butane and VPy = 4-vinylpyridine) (RuVPy), was analyzed.
Results showed that this compound led to a mortality rate of 50% of HEp-2 cell
with 120 +/- 10 MUmol L(-1), indicating its high toxicity. Then, to prove if its
mode of action is associated with its interaction with cell membranes, Langmuir
monolayers were used as a membrane model. RuVPy had a strong effect on the
surface pressure isotherms, especially on the elastic properties of both the
zwitterionic dipalmitoylphosphatidylcholine (DPPC) and the negatively charged
dipalmitoylphosphatidylglycerol (DPPG) phospholipids. These data were confirmed
by polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS).
In addition, interactions between the positive group from RuVPy and the phosphate
group from the phospholipids were corroborated by density functional theory (DFT)
calculations, allowing the determination of the Ru complex orientation at the air
water interface. Although possible contributions from receptors or other cell
components cannot be discarded, the results reported here represent evidence for
significant effects on the cell membranes which are probably associated with the
high toxicity of RuVPy.
PMID- 25133574
TI - A possible link between food and mood: dietary impact on gut microbiota and
behavior in BALB/c mice.
AB - Major depressive disorder is a debilitating disease in the Western World. A
western diet high in saturated fat and refined sugar seems to play an important
part in disease development. Therefore, this study is aimed at investigating
whether saturated fat or sucrose predisposes mice to develop behavioral symptoms
which can be interpreted as depression-like, and the possible influence of the
gut microbiota (GM) in this. Fourty-two mice were randomly assigned to one of
three experimental diets, a high-fat, a high-sucrose or a control diet for
thirteen weeks. Mice on high-fat diet gained more weight (p = 0.00009), displayed
significantly less burrowing behavior than the control mice (p = 0.034), and
showed decreased memory in the Morris water maze test compared to mice on high
sucrose diet (p = 0.031). Mice on high-sucrose diet burrowed less goal-oriented,
showed greater latency to first bout of immobility in the forced swim test when
compared to control mice (p = 0.039) and high-fat fed mice (p = 0.013), and
displayed less anxiety than mice on high-fat diet in the triple test (p = 0.009).
Behavioral changes were accompanied by a significant change in GM composition of
mice fed a high-fat diet, while no difference between diet groups was observed
for sucrose preferences, LPS, cholesterol, HbA1c, BDNF and the cytokines IL
1alpha, IL-1beta, IL-6, IL-10, IL-12(p70), IL-17 and TNF-alpha. A series of
correlations was found between GM, behavior, BDNF and inflammatory mediators. In
conclusion, the study shows that dietary fat and sucrose affect behavior,
sometimes in opposite directions, and suggests a possible association between GM
and behavior.
PMID- 25133575
TI - Cloning and characterization of a Phragmites australis phytochelatin synthase
(PaPCS) and achieving Cd tolerance in tall fescue.
AB - The production of phytochelatins (PCs) provides an important means for plants to
achieve tolerance to cadmium (Cd) toxicity. A reed gene encoding PC synthase
(PaPCS) was isolated and its function tested through its heterologous expression
in a strain of yeast sensitive to Cd. Subsequently, the Cd sensitive and high
biomass accumulating species tall fescue was transformed either with PaPCS or
PaGCS (a glutamyl cysteine synthetase gene of reed) on their own (single
transformants), or with both genes together in the same transgene cassette
(double transformant). The single and double transformants showed greater Cd
tolerance and accumulated more Cd and PC than wild type plants, and their Cd
leaf/root ratio content was higher. The ranking in terms of Cd and PC content for
the various transgenic lines was double transformants>PaGCS single
transformants>PaPCS single transformants>wild type. Thus PaGCS appears to exert a
greater influence than PaPCS over PC synthesis and Cd tolerance/accumulation. The
double transformant has interesting potential for phytoremediation.
PMID- 25133576
TI - The burden of influenza and RSV among inpatients and outpatients in rural western
Kenya, 2009-2012.
AB - BACKGROUND: In Kenya, detailed data on the age-specific burden of influenza and
RSV are essential to inform use of limited vaccination and treatment resources.
METHODS: We analyzed surveillance data from August 2009 to July 2012 for
hospitalized severe acute respiratory illness (SARI) and outpatient influenza
like illness (ILI) at two health facilities in western Kenya to estimate the
burden of influenza and respiratory syncytial virus (RSV). Incidence rates were
estimated by dividing the number of cases with laboratory-confirmed virus
infections by the mid-year population. Rates were adjusted for healthcare-seeking
behavior, and to account for patients who met the SARI/ILI case definitions but
were not tested. RESULTS: The average annual incidence of influenza-associated
SARI hospitalization per 1,000 persons was 2.7 (95% CI 1.8-3.9) among children <5
years and 0.3 (95% CI 0.2-0.4) among persons >=5 years; for RSV-associated SARI
hospitalization, it was 5.2 (95% CI 4.0-6.8) among children <5 years and 0.1 (95%
CI 0.0-0.2) among persons >=5 years. The incidence of influenza-associated
medically-attended ILI per 1,000 was 24.0 (95% CI 16.6-34.7) among children <5
years and 3.8 (95% CI 2.6-5.7) among persons >=5 years. The incidence of RSV
associated medically-attended ILI was 24.6 (95% CI 17.0-35.4) among children <5
years and 0.8 (95% CI 0.3-1.9) among persons >=5 years. CONCLUSIONS: Influenza
and RSV both exact an important burden in children. This highlights the possible
value of influenza vaccines, and future RSV vaccines, for Kenyan children.
PMID- 25133577
TI - Voxel-based MRI intensitometry reveals extent of cerebral white matter pathology
in amyotrophic lateral sclerosis.
AB - Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of upper
and lower motor neurons. Advanced MRI techniques such as diffusion tensor imaging
have shown great potential in capturing a common white matter pathology. However
the sensitivity is variable and diffusion tensor imaging is not yet applicable to
the routine clinical environment. Voxel-based morphometry (VBM) has revealed grey
matter changes in ALS, but the bias-reducing algorithms inherent to traditional
VBM are not optimized for the assessment of the white matter changes. We have
developed a novel approach to white matter analysis, namely voxel-based
intensitometry (VBI). High resolution T1-weighted MRI was acquired at 1.5 Tesla
in 30 ALS patients and 37 age-matched healthy controls. VBI analysis at the group
level revealed widespread white matter intensity increases in the corticospinal
tracts, corpus callosum, sub-central, frontal and occipital white matter tracts
and cerebellum. VBI results correlated with disease severity (ALSFRS-R) and
patterns of cerebral involvement differed between bulbar- and limb-onset. VBI
would be easily translatable to the routine clinical environment, and once
optimized for individual analysis offers significant biomarker potential in ALS.
PMID- 25133578
TI - Stable, covalent attachment of laminin to microposts improves the contractility
of mouse neonatal cardiomyocytes.
AB - The mechanical output of contracting cardiomyocytes, the muscle cells of the
heart, relates to healthy and disease states of the heart. Culturing
cardiomyocytes on arrays of elastomeric microposts can enable inexpensive and
high-throughput studies of heart disease at the single-cell level. However,
cardiomyocytes weakly adhere to these microposts, which limits the possibility of
using biomechanical assays of single cardiomyocytes to study heart disease. We
hypothesized that a stable covalent attachment of laminin to the surface of
microposts improves cardiomyocyte contractility. We cultured cells on
polydimethylsiloxane microposts with laminin covalently bonded with the
organosilanes 3-glycidoxypropyltrimethoxysilane and 3-aminopropyltriethoxysilane
with glutaraldehyde. We measured displacement of microposts induced by the
contractility of mouse neonatal cardiomyocytes, which attach better than mature
cardiomyocytes to substrates. We observed time-dependent changes in contractile
parameters such as micropost deformation, contractility rates, contraction and
relaxation speeds, and the times of contractions. These parameters were affected
by the density of laminin on microposts and by the stability of laminin binding
to micropost surfaces. Organosilane-mediated binding resulted in higher laminin
surface density and laminin binding stability. 3-glycidoxypropyltrimethoxysilane
provided the highest laminin density but did not provide stable protein binding
with time. Higher surface protein binding stability and strength were observed
with 3-aminopropyltriethoxysilane with glutaraldehyde. In cultured
cardiomyocytes, contractility rate, contraction speeds, and contraction time
increased with higher laminin stability. Given these variations in contractile
function, we conclude that binding of laminin to microposts via 3
aminopropyltriethoxysilane with glutaraldehyde improves contractility observed by
an increase in beating rate and contraction speed as it occurs during the
postnatal maturation of cardiomyocytes. This approach is promising for future
studies to mimic in vivo tissue environments.
PMID- 25133579
TI - Visualization of mouse neuronal ganglia infected by Herpes Simplex Virus 1 (HSV
1) using multimodal non-linear optical microscopy.
AB - Herpes simplex virus 1 (HSV-1) is a neurotropic virus that causes skin lesions
and goes on to enter a latent state in neurons of the trigeminal ganglia.
Following stress, the virus may reactivate from latency leading to recurrent
lesions. The in situ study of neuronal infections by HSV-1 is critical to
understanding the mechanisms involved in the biology of this virus and how it
causes disease; however, this normally requires fixation and sectioning of the
target tissues followed by treatment with contrast agents to visualize key
structures, which can lead to artifacts. To further our ability to study HSV-1
neuropathogenesis, we have generated a recombinant virus expressing a second
generation red fluorescent protein (mCherry), which behaves like the parental
virus in vivo. By optimizing the application of a multimodal non-linear optical
microscopy platform, we have successfully visualized in unsectioned trigeminal
ganglia of mice both infected cells by two-photon fluorescence microscopy, and
myelinated axons of uninfected surrounding cells by coherent anti-Stokes Raman
scattering (CARS) microscopy. These results represent the first report of CARS
microscopy being combined with 2-photon fluorescence microscopy to visualize
virus-infected cells deep within unsectioned explanted tissue, and demonstrate
the application of multimodal non-linear optical microscopy for high spatial
resolution biological imaging of tissues without the use of stains or fixatives.
PMID- 25133580
TI - Expression of wheat high molecular weight glutenin subunit 1Bx is affected by
large insertions and deletions located in the upstream flanking sequences.
AB - To better understand the transcriptional regulation of high molecular weight
glutenin subunit (HMW-GS) expression, we isolated four Glu-1Bx promoters from six
wheat cultivars exhibiting diverse protein expression levels. The activities of
the diverse Glu-1Bx promoters were tested and compared with beta-glucuronidase
(GUS) reporter fusions. Although all the full-length Glu-1Bx promoters showed
endosperm-specific activities, the strongest GUS activity was observed with the
1Bx7OE promoter in both transient expression assays and stable transgenic rice
lines. A 43 bp insertion in the 1Bx7OE promoter, which is absent in the 1Bx7
promoter, led to enhanced expression. Analysis of promoter deletion constructs
confirmed that a 185 bp MITE (miniature inverted-repeat transposable element) in
the 1Bx14 promoter had a weak positive effect on Glu-1Bx expression, and a 54 bp
deletion in the 1Bx13 promoter reduced endosperm-specific activity. To
investigate the effect of the 43 bp insertion in the 1Bx7OE promoter, a
functional marker was developed to screen 505 Chinese varieties and 160 European
varieties, and only 1Bx7-type varieties harboring the 43 bp insertion in their
promoters showed similar overexpression patterns. Hence, the 1Bx7OE promoter
should be important tool in crop genetic engineering as well as in molecular
assisted breeding.
PMID- 25133582
TI - Gemini surfactants affect the structure, stability, and activity of ribonuclease
Sa.
AB - Gemini surfactants have important advantages, e.g., low micromolar CMCs and slow
millisecond monomer <-> micelle kinetics, for membrane mimetics and for
delivering nucleic acids for gene therapy or RNA silencing. However, as a
prerequisite, it is important to characterize interactions occurring between
Gemini surfactants and proteins. Here NMR and CD spectroscopies are employed to
investigate the interactions of cationic Gemini surfactants with RNase Sa, a
negatively charged ribonuclease. We find that RNase Sa binds Gemini surfactant
monomers and micelles at pH values above 4 to form aggregates. Below pH 4, where
the protein is positively charged, these aggregates dissolve and interactions are
undetectable. Thermal denaturation experiments show that surfactant lowers RNase
Sa's conformational stability, suggesting that surfactant binds the protein's
denatured state preferentially. Finally, Gemini surfactants were found to bind
RNA, leading to the formation of large complexes. Interestingly, Gemini
surfactant binding did not prevent RNase Sa from cleaving RNA.
PMID- 25133581
TI - Next-generation sequencing of colorectal cancers in chinese: identification of a
recurrent frame-shift and gain-of-function Indel mutation in the TFDP1 gene.
AB - Abstract Re-sequencing of target genes is a highly effective approach for
identifying mutations in cancers. Mutations, including indels (insertions,
deletions, and the combination of the two), play important roles in
carcinogenesis. Combining genomic DNA capture using high-density oligonucleotide
microarrays (NimbleGen, Inc.) with next-generation high-throughput sequencing, we
identified approximately 1600 indels for colorectal cancers in the Chinese
population. Among them, 5 indels were localized to exonic regions of genes,
including the TFDP1 (transcription factor Dp-1) gene. TFDP1 is an important
transcription factor that coordinates with E2F proteins, thereby promoting
transcription of E2F target genes and regulating the cell cycle and
differentiation. We report here the identification of a recurrent frame-shift
indel mutation (named indel84) in the TFDP1 gene in colorectal cancers by next
generation sequencing. We found in a validation set that TFDP1 indel84 is present
in 70% of colorectal cancer (CRC) tissues. Wild-type TFDP1 encodes a protein of
410 amino acids with a potential DNA binding site at its N-terminal followed by
several functional protein domains. The TFDP1 indel cDNA would generate an
alternative TFDP1 protein missing the first 120 amino acids and potentially
affecting the DNA binding domain. We further demonstrated that the TFDP1 indel84
mutation generated a gain-of-function phenotype by increasing cell proliferation,
migration, and invasion of CRC cells. Our study identified a key molecular event
for CRC that might have great diagnostic and therapeutic potentials.
PMID- 25133583
TI - TRPC1 contributes to the Ca2+-dependent regulation of adenylate cyclases.
AB - SOCE (store-operated Ca2+ entry) is mediated via specific plasma membrane
channels in response to ER (endoplasmic reticulum) Ca2+ store depletion. This
route of Ca2+ entry is central to the dynamic interplay between Ca2+ and cAMP
signalling in regulating the activity of Ca2+-sensitive adenylate cyclase
isoforms (AC1, AC5, AC6 and AC8). Two proteins have been identified as key
components of SOCE: STIM1 (stromal interaction molecule 1), which senses ER Ca2+
store content and translocates to the plasma membrane upon store depletion, where
it then activates Orai1, the pore-forming component of the CRAC (Ca2+ release
activated Ca2+) channel. Previous studies reported that co-expression of STIM1
and Orai1 in HEK-293 (human embryonic kidney 293) cells enhances Ca2+-stimulated
AC8 activity and that AC8 and Orai1 directly interact to enhance this regulation.
Nonetheless, the additional involvement of TRPC (transient receptor potential
canonical) channels in SOCE has also been proposed. In the present study, we
evaluate the contribution of TRPC1 to SOCE-mediated regulation of Ca2+-sensitive
ACs in HEK-293 cells stably expressing AC8 (HEK-AC8) and HSG (human submandibular
gland) cells expressing an endogenous Ca2+-inhibited AC6. We demonstrate a role
for TRPC1 as an integral component of SOCE, alongside STIM1 and Orai1, in
regulating Ca2+ fluxes within AC microdomains and influencing cAMP production.
PMID- 25133585
TI - Eukaryotic expression system Pichia pastoris affects the lipase catalytic
properties: a monolayer study.
AB - Recombinant DNA methods are being widely used to express proteins in both
prokaryotic and eukaryotic cells for both fundamental and applied research
purposes. Expressed protein must be well characterized to be sure that it retains
the same properties as the native one, especially when expressed protein will be
used in the pharmaceutical field. In this aim, interfacial and kinetic properties
of native, untagged recombinant and tagged recombinant forms of a pancreatic
lipase were compared using the monomolecular film technique. Turkey pancreatic
lipase (TPL) was chosen as model. A kinetic study on the dependence of the
stereoselectivity of these three forms on the surface pressure was performed
using three dicaprin isomers spread in the form of monomolecular films at the air
water interface. The heterologous expression and the N-His-tag extension were
found to modify the pressure preference and decrease the catalytic hydrolysis
rate of three dicaprin isomers. Besides, the heterologous expression was found to
change the TPL regioselectivity without affecting its stereospecificity contrary
to the N-tag extension which retained that regioselectivity and changed the
stereospecificity at high surface pressures. The study of parameters, termed
Recombinant expression Effects on Catalysis (REC), N-Tag Effects on Catalysis
(TEC), and N-Tag and Recombinant expression Effects on Catalysis (TREC) showed
that the heterologous expression effects on the catalytic properties of the TPL
were more deleterious than the presence of an N-terminal tag extension.
PMID- 25133586
TI - Photodissociation of pyrene cations: structure and energetics from C16H10(+) to
C14(+) and almost everything in between.
AB - The unimolecular dissociation of the pyrene radical cation, C16H10(+*), has been
explored using a combination of computational techniques and experimental
approaches, such as multiple photon absorption in the cold ion trap Piege a Ions
pour la Recherche et l'Etude de Nouvelles Especes Astrochimiques (PIRENEA) and
imaging photoelectron photoion coincidence spectrometry (iPEPICO). In total, 22
reactions, involving the fragmentation cascade (H, C2H2, and C4H2 loss) from the
pyrene radical cation down to the C14(+*) fragment ion, have been studied using
PIRENEA. Branching ratios have been measured for reactions from C16H10(+*),
C16H8(+*), and C16H5(+). Density functional theory calculations of the
fragmentation pathways observed experimentally and postulated theoretically lead
to 17 unique structures. One important prediction is the opening of the pyrene
ring system starting from the C16H4(+*) radical. In the iPEPICO experiments, only
two reactions could be studied, namely, R1 C16H10(+*) -> C16H9(+) + H (m/z = 201)
and R2 C16H9(+) -> C16H8(+*) + H (m/z = 200). The activation energies for these
reactions were determined to be 5.4 +/- 1.2 and 3.3 +/- 1.1 eV, respectively.
PMID- 25133584
TI - Physiological and genomic features of a novel sulfur-oxidizing
gammaproteobacterium belonging to a previously uncultivated symbiotic lineage
isolated from a hydrothermal vent.
AB - Strain Hiromi 1, a sulfur-oxidizing gammaproteobacterium was isolated from a
hydrothermal vent chimney in the Okinawa Trough and represents a novel genus that
may include a phylogenetic group found as endosymbionts of deep-sea gastropods.
The SSU rRNA gene sequence similarity between strain Hiromi 1 and the gastropod
endosymbionts was approximately 97%. The strain was shown to grow both
chemolithoautotrophically and chemolithoheterotrophically with an energy
metabolism of sulfur oxidation and O2 or nitrate reduction. Under
chemolithoheterotrophic growth conditions, the strain utilized organic acids and
proteinaceous compounds as the carbon and/or nitrogen sources but not the energy
source. Various sugars did not support growth as a sole carbon source. The
observation of chemolithoheterotrophy in this strain is in line with metagenomic
analyses of endosymbionts suggesting the occurrence of chemolithoheterotrophy in
gammaproteobacterial symbionts. Chemolithoheterotrophy and the presence of
homologous genes for virulence- and quorum sensing-related functions suggest that
the sulfur-oxidizing chomolithotrophic microbes seek animal bodies and microbial
biofilm formation to obtain supplemental organic carbons in hydrothermal
ecosystems.
PMID- 25133587
TI - Diastereoselective N-sulfonylaminoalkenylation of azulenes from terminal alkynes
and azides via N-sulfonyl-1,2,3-triazoles.
AB - The development of rhodium-catalyzed diastereoselective N
sulfonylaminoalkenylation of azulenes using N-sulfonyltriazoles is described.
This procedure can be successfully applied to rhodium-catalyzed
diastereoselective N-sulfonylaminoalkenylation of azulenes starting from terminal
alkynes and N-sulfonylazides via a three-component semi-one-pot process.
PMID- 25133588
TI - Reproducibility and consistency of proteomic experiments on natural populations
of a non-model aquatic insect.
AB - Population proteomics has a great potential to address evolutionary and
ecological questions, but its use in wild populations of non-model organisms is
hampered by uncontrolled sources of variation. Here we compare the response to
temperature extremes of two geographically distant populations of a diving beetle
species (Agabus ramblae) using 2-D DIGE. After one week of acclimation in the
laboratory under standard conditions, a third of the specimens of each population
were placed at either 4 or 27 degrees C for 12 h, with another third left as a
control. We then compared the protein expression level of three replicated
samples of 2-3 specimens for each treatment. Within each population, variation
between replicated samples of the same treatment was always lower than variation
between treatments, except for some control samples that retained a wider range
of expression levels. The two populations had a similar response, without
significant differences in the number of protein spots over- or under-expressed
in the pairwise comparisons between treatments. We identified exemplary proteins
among those differently expressed between treatments, which proved to be proteins
known to be related to thermal response or stress. Overall, our results indicate
that specimens collected in the wild are suitable for proteomic analyses, as the
additional sources of variation were not enough to mask the consistency and
reproducibility of the response to the temperature treatments.
PMID- 25133589
TI - Exploring the mechanisms of differentiation, dedifferentiation, reprogramming and
transdifferentiation.
AB - We explored the underlying mechanisms of differentiation, dedifferentiation,
reprogramming and transdifferentiation (cell type switchings) from landscape and
flux perspectives. Lineage reprogramming is a new regenerative method to convert
a matured cell into another cell including direct transdifferentiation without
undergoing a pluripotent cell state and indirect transdifferentiation with an
initial dedifferentiation-reversion (reprogramming) to a pluripotent cell state.
Each cell type is quantified by a distinct valley on the potential landscape with
higher probability. We investigated three driving forces for cell fate decision
making: stochastic fluctuations, gene regulation and induction, which can lead to
cell type switchings. We showed that under the driving forces the direct
transdifferentiation process proceeds from a differentiated cell valley to
another differentiated cell valley through either a distinct stable intermediate
state or a certain series of unstable indeterminate states. The dedifferentiation
process proceeds through a pluripotent cell state. Barrier height and the
corresponding escape time from the valley on the landscape can be used to
quantify the stability and efficiency of cell type switchings. We also uncovered
the mechanisms of the underlying processes by quantifying the dominant biological
paths of cell type switchings on the potential landscape. The dynamics of cell
type switchings are determined by both landscape gradient and flux. The flux can
lead to the deviations of the dominant biological paths for cell type switchings
from the naively expected landscape gradient path. As a result, the corresponding
dominant paths of cell type switchings are irreversible. We also classified the
mechanisms of cell fate development from our landscape theory: super-critical
pitchfork bifurcation, sub-critical pitchfork bifurcation, sub-critical pitchfork
with two saddle-node bifurcation, and saddle-node bifurcation. Our model showed
good agreements with the experiments. It provides a general framework to explore
the mechanisms of differentiation, dedifferentiation, reprogramming and
transdifferentiation.
PMID- 25133591
TI - Potential of cycloaddition reactions to generate cytotoxic metal drugs in vitro.
AB - Severe general toxicity issues blight many chemotherapeutics utilized in the
treatment of cancers, resulting in the need for more selective drugs able to
exert their biological activity at only the required location(s). Toward this
aim, we report the development of an organometallic ruthenium compound,
functionalized through a eta(6)-bound arene ligand with a bicyclononyne
derivative, able to participate in strain-promoted cycloaddition reactions with
tetrazines. We show that combination of the ruthenium compound with a ditetrazine
in biological media results in the in situ formation of a dinuclear molecule that
is more cytotoxic toward cancer cells than the starting mononuclear ruthenium
compound and tetrazine components. Such an approach may be extended to in vivo
applications to construct a cytotoxic metallodrug at a tumor site, providing a
novel approach toward the turn-on cytotoxicity of metallodrugs in the treatment
of cancer.
PMID- 25133590
TI - Lactobacillus casei reduces susceptibility to type 2 diabetes via microbiota
mediated body chloride ion influx.
AB - Gut microbiota mediated low-grade inflammation is involved in the onset of type 2
diabetes (T2DM). In this study, we used a high fat sucrose (HFS) diet-induced pre
insulin resistance and a low dose-STZ HFS rat models to study the effect and
mechanism of Lactobacillus casei Zhang in protecting against T2DM onset.
Hyperglycemia was favorably suppressed by L. casei Zhang treatment. Moreover, the
hyperglycemia was connected with type 1 immune response, high plasma bile acids
and urine chloride ion loss. This chloride ion loss was significantly prevented
by L. casei via upregulating of chloride ion-dependent genes (ClC1-7, GlyRalpha1,
SLC26A3, SLC26A6, GABAAalpha1, Bestrophin-3 and CFTR). A shift in the caecal
microflora, particularly the reduction of bile acid 7alpha-dehydroxylating
bacteria, and fecal bile acid profiles also occurred. These change coincided with
organ chloride influx. Thus, we postulate that the prevention of T2DM onset by L.
casei Zhang may be via a microbiota-based bile acid-chloride exchange mechanism.
PMID- 25133592
TI - Redox and metabolic regulation of stem/progenitor cells and their niche.
AB - Stem cells are defined as cells that have the capacity to self-renew and exhibit
multipotency or pluripotency, whereas progenitor cells are committed to selected
lineages but retain their self-renewal capacity. The stem or progenitor cell
niche refers to the microenvironment of the regenerative cells in the bone marrow
(BM) or other tissues such as the heart. It can regulate self-renewal,
differentiation, migration, and proliferation of regenerative stem/progenitor
cells. The precise regulatory mechanisms by which the niche and the
stem/progenitor cells interact are an active area of research. Reactive oxygen
species (ROS) are one such niche regulatory mechanism. Quiescent stem cells in a
hypoxic niche exhibit low ROS levels due to well-organized antioxidant defense
systems, which protect stem cells from extrinsic oxidative stress, whereas high
levels of ROS promote the differentiation or migration of stem/progenitor cells.
In pathophysiological conditions such as diabetes, BM niche dysfunction induced
by oxidative stress contributes to the reduction of the angiogenic and
vasculogenic potential of BM-derived regenerative cells, thereby leading to less
efficient healing and revascularization. Cells have evolved mechanisms to fine
tune ROS levels by tightly regulated metabolic pathways such as glycolysis rather
than oxidative phosphorylation to reduce oxidative stress. This Forum will
summarize the recent progress regarding the redox and metabolic regulation of
hematopoietic and cardiac stem/progenitor cells, as well as their niche
interactions involved in tissue regeneration and repair under physiological and
pathological conditions. Understanding such mechanisms will contribute to the
development of novel therapeutic strategies to enhance regeneration and repair of
diseased tissues.
PMID- 25133593
TI - Synergistic and antagonistic effects of thermal shock, air exposure, and fishing
capture on the physiological stress of Squilla mantis (Stomatopoda).
AB - This study is aimed at assessing the effects of multiple stressors (thermal
shock, fishing capture, and exposure to air) on the benthic stomatopod Squilla
mantis, a burrowing crustacean quite widespread in the Mediterranean Sea.
Laboratory analyses were carried out to explore the physiological impairment
onset over time, based on emersion and thermal shocks, on farmed individuals.
Parallel field-based studies were carried out to also investigate the role of
fishing (i.e., otter trawling) in inducing physiological imbalance in different
seasonal conditions. The dynamics of physiological recovery from physiological
disruption were also studied. Physiological stress was assessed by analysing
hemolymph metabolites (L-Lactate, D-glucose, ammonia, and H+), as well as
glycogen concentration in muscle tissues. The experiments were carried out
according to a factorial scheme considering the three factors (thermal shock,
fishing capture, and exposure to air) at two fixed levels in order to explore
possible synergistic, additive, or antagonistic effects among factors. Additive
effects on physiological parameters were mainly detected when the three factors
interacted together while synergistic effects were found as effect of the
combination of two factors. This finding highlights that the physiological
adaptive and maladaptive processes induced by the stressors result in a dynamic
response that may encounter physiological limits when high stress levels are
sustained. Thus, a further increase in the physiological parameters due to
synergies cannot be reached. Moreover, when critical limits are encountered,
mortality occurs and physiological parameters reflect the response of the last
survivors. In the light of our mortality studies, thermal shock and exposure to
air have the main effect on the survival of S. mantis only on trawled
individuals, while lab-farmed individuals did not show any mortality during
exposure to air until after 2 hours.
PMID- 25133594
TI - Spontaneous high piezoelectricity in poly(vinylidene fluoride) nanoribbons
produced by iterative thermal size reduction technique.
AB - We produced kilometer-long, endlessly parallel, spontaneously piezoelectric and
thermally stable poly(vinylidene fluoride) (PVDF) micro- and nanoribbons using
iterative size reduction technique based on thermal fiber drawing. Because of
high stress and temperature used in thermal drawing process, we obtained
spontaneously polar gamma phase PVDF micro- and nanoribbons without electrical
poling process. On the basis of X-ray diffraction (XRD) analysis, we observed
that PVDF micro- and nanoribbons are thermally stable and conserve the polar
gamma phase even after being exposed to heat treatment above the melting point of
PVDF. Phase transition mechanism is investigated and explained using ab initio
calculations. We measured an average effective piezoelectric constant as -58.5
pm/V from a single PVDF nanoribbon using a piezo evaluation system along with an
atomic force microscope. PVDF nanoribbons are promising structures for
constructing devices such as highly efficient energy generators, large area
pressure sensors, artificial muscle and skin, due to the unique geometry and
extended lengths, high polar phase content, high thermal stability and high
piezoelectric coefficient. We demonstrated two proof of principle devices for
energy harvesting and sensing applications with a 60 V open circuit peak voltage
and 10 MUA peak short-circuit current output.
PMID- 25133595
TI - Low-cost experimentation for the study of droplet microfluidics.
AB - The continued growth of microfluidics into industry settings in areas such as
point-of-care diagnostics and targeted therapeutics necessitates a workforce
trained in microfluidic technologies and experimental methods. Laboratory courses
for students at the university and high school levels will require cost-effective
in-class demonstrations that instruct in chip design, fabrication, and
experimentation at the microscale. We present a hand-operated pressure pumping
system to form monodisperse picoliter to nanoliter droplet streams at low cost,
and a series of exercises aimed at instructing in the specific art of droplet
formation. Using this setup, the student is able to generate and observe the
modes of droplet formation in flow-focusing devices, and the effect of device
dimensions on the characteristics of formed droplets. Lastly, at ultra-low cost
we demonstrate large plug formation in a T-junction using coffee stirrers as a
master mold substitute. Our method reduces the cost of experimentation to enable
intuitive instruction in droplet formation, with additional implications for
creating droplets in the field or at point-of-care.
PMID- 25133596
TI - Finite element study of human pelvis model in side impact for Chinese adult
occupants.
AB - OBJECTIVE: The occupant's pelvis is very vulnerable to side collision in road
accidents. Finite element (FE) studies on pelvic injury help to design occupant
protection devices to improve vehicle safety. This study was aimed to develop a
highly biofidelic pelvis model of Chinese adults and assess its sensitivity to
variations in pelvis cortical bone thickness, bone material properties, and
loading conditions. METHODS: In this study, 4 different FE models of the pelvis
were developed from the computed tomography (CT) data of a volunteer representing
the 50th percentile Chinese male. Two of them were meshed using entirely
hexahedral elements with variable and constant cortical thickness distribution
(the V-Hex and C-Hex models), and the others were modeled with hexahedral
elements for cancellous bone and variable or constant thickness shell elements
for cortical bone (the V-HS and C-HS models). In model developments, the semi
automatic multiblock meshing approach was employed to maintain the pelvis
geometric curvature and generate a high-quality hexahedral mesh. Then, several
simulations with postmortem human subjects (PMHS) tests were performed to obtain
the most accurate model in predicting pelvic injury. Based on the most accurate
model, sensitivity studies were conducted to analyze the effects of the cortex
thickness, Young's modulus of the cortical and cancellous bone, impactor
velocity, and impactor with or without padding on the biomechanical responses and
injuries of pelvis. RESULTS: The results indicate that the models with variable
cortical bone thickness can give more accurate predictions than those with
constant cortical thickness. Both the V-Hex and V-HS models are favorable for
simulating pelvic response and injury, but the simulation results of the V-Hex
model agree with the tests better. The sensitivity study shows that pelvic
response is more sensitive to alterations in the Young's modulus of cortical bone
than cancellous bone. Compared to failure displacement, peak force is more
sensitive to the cortical bone thickness. However, displacement is more sensitive
to the Young's modulus of cancellous bone than peak force. The padding attached
on the impactor plays a significant role in absorbing the impact energy and
alleviating pelvic injury. CONCLUSIONS: The all-hex meshing method with variable
cortical bone thickness has the highest accuracy but is time-consuming. The
cortical bone plays a determining role in resisting pelvic fracture. Peak impact
force appears to be a reasonable injury predictor for pelvic injury assessment.
Some appropriate energy absorbers installed in the car door can significantly
reduce pelvic injury and will be beneficial for occupant protection.
PMID- 25133597
TI - What's new in shock? May 2014.
PMID- 25133598
TI - The traumatic hemostasis and oxygenation research network remote damage control
resuscitation (RDCR) symposium.
PMID- 25133599
TI - Resuscitative endovascular balloon occlusion of the aorta: a gap analysis of
severely injured UK combat casualties.
AB - The control of torso and junctional zone bleeding in combat casualties is
particularly challenging because of its noncompressible nature. Resuscitative
endovascular balloon occlusion of the aorta (REBOA) has demonstrated promise in
translational large animal and early clinical series as an effective
resuscitation and hemorrhage control adjunct. However, it is unknown what
proportion of combat casualties has an injury pattern and clinical course that is
amenable to REBOA deployment. The prospective UK Joint Theatre Trauma Registry
was used to retrospectively identify all UK military personnel who has sustained
a severe combat injury, defined as an Abbreviated Injury Scale of three or
greater, in the course of 10 years. Patients were then divided into three groups
based on Abbreviated Injury Scale injury pattern: no indications for REBOA,
contraindications (mediastinal, cervical, and axillary hemorrhage), and
indications (torso and pelvic hemorrhage). From a total of 1,317 patients, 925
(70.2%) had no indication, 148 (11.2%) had a contraindication, and 244 (18.5%)
had an indication for REBOA. Within the group with indications for REBOA, there
were 174 deaths: 79 at the point of wounding, 66 en route to hospital, and 29 in
hospital deaths. The median (interquartile range) time to death in patients dying
en route was 75 (42-109) min, and the median prehospital time for casualties
admitted to hospital was 61 (34-89) min. One-in-five severely injured UK combat
casualties have a focus of hemorrhage in the abdomen or pelvic junctional region
potentially amenable to REBOA deployment. The UK military should explore REBOA as
a potential en route hemorrhage control and resuscitation adjunct.
PMID- 25133600
TI - Impact of body mass on outcomes of geriatric postoperative acute kidney injury
patients.
AB - BACKGROUND: Acute kidney injury (AKI) frequently occurs in hospitalized patients,
particularly in the elderly. However, studies on outcome-modifying factors in
geriatric patients with AKI are absent, especially the influence of body mass
index (BMI). METHODS: We performed a retrospective analysis of a prospectively
collected multicenter observational cohort, which enrolled elderly (>=65 years)
who developed AKI after major surgery in the intensive care units. We analyzed in
hospital mortality within BMI category utilizing Cox proportional hazard
regression analysis and generalized additive modeling. RESULTS: Data of a total
of 2,015 postoperative elderly patients were retrieved and analyzed. Generalized
additive modeling showed that elderly AKI patients with a BMI between 21 and 31
kg/m(2) ("normal") had a lower mortality risk than those with a BMI of less than
21 kg/m(2) ("underweight") or 31 kg/m(2) or greater ("obese"). Both "underweight"
and "obese" individuals had a greater risk of mortality compared with patients
with "normal" BMI. CONCLUSIONS: The U-shaped association of BMI with hospital
mortality in geriatric AKI patients contains a widened base and a shifted nadir
comparing with chronic dialysis and other AKI patients. This finding is
interesting and warrants our attention.
PMID- 25133601
TI - Dried platelets in a swine model of liver injury.
AB - INTRODUCTION: Lyophilization may facilitate production of a safe, portable,
easily storable, and transportable source of platelets for bleeding patients. The
objective of this study was to examine the impact of lyophilized human and
porcine platelets in a swine liver injury model of nonsurgical hemorrhage.
METHODS: Anesthetized pigs (40 kg) had a controlled 35% total blood volume bleed
from the right jugular vein followed by cooling to 35 degrees C and resuscitation
with Ringer's lactate to achieve a 3:1 blood withdrawal resuscitation. Through a
midline laparotomy, the liver was injured with two standardized 5 * 5-cm grids
with lacerations 1 cm apart and 0.5 cm deep. After 2 min of uncontrolled
hemorrhage, the animals were treated with placebo (n = 5), lyophilized human (n =
5, HP), or swine platelets (n = 5, SP). At 15 min, shed blood was calculated. The
animals then underwent abdominal closure. At 48 h, the animals were killed for
histopathologic evaluation of the lung, kidney, and heart. RESULTS:
Intraoperative blood loss at 15 min was significantly higher in the HP arm (SP:
4.9 +/- 2.9 mL/kg, HP: 12.3 +/- 4.7 mL/kg, and control: 6.1 +/- 2.5 mL/kg; P =
0.013). Mortality at 48 h was 20% in all three arms, due to uncontrolled intra
abdominal bleeding. At the time the animals were killed, SP animals had a
significantly higher hematocrit (SP: 22.0% +/- 3.0%, HP: 15.1% +/- 4.9%, and
control: 13.9% +/- 0.6%; P = 0.026). No significant difference was found in
platelet count (SP: 319.3 +/- 62.1 * 10(3)/uL, HP:361.5 +/- 133.6 * 10(3)/uL, and
control: 242.7 +/- 42.5 * 10(3)/uL; P = 0.259). Histopathology of kidneys, lungs,
and heart demonstrated no evidence of thromboembolic complications. CONCLUSION:
In this swine model of liver injury, human lyophilized platelets increased
intraoperative blood loss. With the use of species-specific lyophilized
platelets, however, this effect was abolished, with a decrease in blood loss at
48 h after injury.
PMID- 25133602
TI - Pleiotropic effects of atorvastatin in experimental sepsis: preservation of beta1
adrenoreceptor signaling in the heart.
PMID- 25133603
TI - In situ chemical oxidation of contaminated groundwater by persulfate:
decomposition by Fe(III)- and Mn(IV)-containing oxides and aquifer materials.
AB - Persulfate (S2O8(2-)) is being used increasingly for in situ chemical oxidation
(ISCO) of organic contaminants in groundwater, despite an incomplete
understanding of the mechanism through which it is converted into reactive
species. In particular, the decomposition of persulfate by naturally occurring
mineral surfaces has not been studied in detail. To gain insight into the
reaction rates and mechanism of persulfate decomposition in the subsurface, and
to identify possible approaches for improving its efficacy, the decomposition of
persulfate was investigated in the presence of pure metal oxides, clays, and
representative aquifer solids collected from field sites in the presence and
absence of benzene. Under conditions typical of groundwater, Fe(III)- and Mn(IV)
oxides catalytically converted persulfate into sulfate radical (SO4(*-)) and
hydroxyl radical (HO(*)) over time scales of several weeks at rates that were 2
20 times faster than those observed in metal-free systems. Amorphous ferrihydrite
was the most reactive iron mineral with respect to persulfate decomposition, with
reaction rates proportional to solid mass and surface area. As a result of
radical chain reactions, the rate of persulfate decomposition increased by as
much as 100 times when benzene concentrations exceeded 0.1 mM. Due to its
relatively slow rate of decomposition in the subsurface, it can be advantageous
to inject persulfate into groundwater, allowing it to migrate to zones of low
hydraulic conductivity where clays, metal oxides, and contaminants will
accelerate its conversion into reactive oxidants.
PMID- 25133606
TI - Formulation, in vitro and in vivo evaluation of halofantrine-loaded solid lipid
microparticles.
AB - Abstract Context: Formulation, characterization, in vitro and in vivo evaluation
of halofantrine-loaded solid lipid microparticles (SLMs). Objective: The
objective of the study was to formulate and evaluate halofantrine-loaded SLMs.
Materials and methods: Formulations of halofantrine-loaded SLMs were prepared by
hot homogenization and thereafter lyophilized and characterized using particle
size, pH stability, loading capacity (LC) and encapsulation efficiency (EE). In
vitro release of halofantrine (Hf) from the optimized SLMs was performed in SIF
and SGF. In vivo study using Peter's Four day suppressive protocol in mice and
the mice thereafter subjected to histological studies in kidney and liver.
Results: Results obtained indicated that EE of 76.32% and 61.43% were obtained
for the SLMs containing 7% and 3% of Hf respectively. The SLMs loaded with 3% of
Hf had the highest yield of 73.33%. Time-dependent pH stability analysis showed
little variations in pH ranging from 3.49 +/- 0.04 to 4.03 +/- 0.05. Discussion:
The SLMs showed pH-dependent release profile; in SIF (43.5% of the drug for each
of H2 and H3) compared with SGF (13 and 18% for H2 and H3 respectively) after 8
h. The optimized SLMs formulation and Halfan(r) produced a percentage reduction
in parasitemia of 72.96% and 85.71% respectively. The histological studies
revealed that the SLMs formulations have no harmful effects on the kidney and
liver. Conclusion: SLMs formulations might be an alternative for patients with
parasitemia as there were no harmful effects on vital organs of the mice.
PMID- 25133605
TI - Increased sensitivity to inflammatory pain induced by subcutaneous formalin
injection in serine racemase knock-out mice.
AB - D-Serine, an endogenous coagonist of the N-methyl-D-aspartate receptor (NMDAR),
is widely distributed in the central nervous system and is synthesized from L
serine by serine racemase (SR). NMDAR plays an important role in pain processing
including central sensitization that eventually causes hyperalgesia. To elucidate
the roles of D-serine and SR in pain transmission, we evaluated the behavioral
changes and spinal nociceptive processing induced by formalin using SR knock-out
(KO) mice. We found that SR is mainly distributed in lamina II of the dorsal horn
of the spinal cord in wild-type (WT) mice. Although the formalin injected
subcutaneously induced the biphasic pain response of licking in SR-KO and WT
mice, the time spent on licking was significantly longer in the SR-KO mice during
the second phase of the formalin test. The number of neurons immunopositive for c
Fos and phosphorylated extracellular signal-regulated kinase (p-ERK), which are
molecular pain markers, in laminae I-II of the ipsilateral dorsal horn was
significantly larger in the SR-KO mice. Immunohistochemical staining revealed
that the distribution of SR changed from being broad to being concentrated in
cell bodies after the formalin injection. On the other hand, the expression level
of the cytosolic SR in the ipsilateral dorsal horn significantly decreased. Oral
administration of 10 mM D-serine in drinking water for one week cancelled the
difference in pain behaviors between WT and SR-KO mice in phase 2 of the formalin
test. These findings demonstrate that the SR-KO mice showed increased sensitivity
to inflammatory pain and the WT mice showed translocation of SR and decreased SR
expression levels after the formalin injection, which suggest a novel
antinociceptive mechanism via SR indicating an important role of D-serine in pain
transmission.
PMID- 25133604
TI - Curation and analysis of multitargeting agents for polypharmacological modeling.
AB - In drug discovery and development, the conventional "single drug, single target"
concept has been shifted to "single drug, multiple targets"--a concept coined as
polypharmacology. For studies in this emerging field, dedicated and high-quality
databases of multitargeting ligands would be exceedingly beneficial. To this end,
we conducted a comprehensive analysis of the structural and chemical/biological
profiles of polypharmacological agents and present a Web-based database
(Polypharma). All of these compounds curated herein have been cocrystallized with
more than one unique protein with intensive reports of their multitargeting
activities. The present study provides more insight of drug multitargeting and is
particularly useful for polypharmacology modeling. This specialized curation has
been made publically available at http:/imdlab.org/polypharma/
PMID- 25133607
TI - Addressing mechanism of fibrillization/aggregation and its prevention in presence
of osmolytes: spectroscopic and calorimetric approach.
AB - Understanding the mechanism of protein fibrillization/aggregation and its
prevention is the basis of development of therapeutic strategies for amyloidosis.
An attempt has been made to understand the nature of interactions of osmolytes L
proline, 4-hydroxy-L-proline, sarcosine and trimethylamine N-oxide with the
different stages of fibrillization of hen egg-white lysozyme by using a
combination of isothermal titration calorimetry, differential scanning
calorimetry, fluorescence spectroscopy, and transmission electron microscopy.
Based on thioflavin T fluorescence emission intensities and microscopic images,
the nucleation, elongation, and saturation phases of fibrillization have been
identified. Isothermal titration calorimetry and differential scanning
calorimetry have enabled a quantitative analysis of the nature of interactions of
these osmolytes with various conformational states of lysozyme at different
stages of fibrillization/aggregation. It is concluded that interaction of the
osmolytes with lysozyme fibrils at both the nucleation and elongation stages are
important steps in the prevention of fibrillization/aggregation. Identification
of the nature of interactions is a key step towards the discovery and synthesis
of target oriented potential inhibitors of these associations. This study is a
first report in which calorimetry has been used to address interaction of
potential inihibitiors with the protein at different stages of fibrillization.
PMID- 25133608
TI - Precise engineering of siRNA delivery vehicles to tumors using polyion complexes
and gold nanoparticles.
AB - For systemic delivery of siRNA to solid tumors, a size-regulated and reversibly
stabilized nanoarchitecture was constructed by using a 20 kDa siRNA-loaded unimer
polyion complex (uPIC) and 20 nm gold nanoparticle (AuNP). The uPIC was
selectively prepared by charge-matched polyionic complexation of a poly(ethylene
glycol)-b-poly(L-lysine) (PEG-PLL) copolymer bearing ~40 positive charges (and
thiol group at the omega-end) with a single siRNA bearing 40 negative charges.
The thiol group at the omega-end of PEG-PLL further enabled successful
conjugation of the uPICs onto the single AuNP through coordinate bonding,
generating a nanoarchitecture (uPIC-AuNP) with a size of 38 nm and a narrow size
distribution. In contrast, mixing thiolated PEG-PLLs and AuNPs produced a large
aggregate in the absence of siRNA, suggesting the essential role of the preformed
uPIC in the formation of nanoarchitecture. The smart uPIC-AuNPs were stable in
serum-containing media and more resistant against heparin-induced counter
polyanion exchange, compared to uPICs alone. On the other hand, the treatment of
uPIC-AuNPs with an intracellular concentration of glutathione substantially
compromised their stability and triggered the release of siRNA, demonstrating the
reversible stability of these nanoarchitectures relative to thiol exchange and
negatively charged AuNP surface. The uPIC-AuNPs efficiently delivered siRNA into
cultured cancer cells, facilitating significant sequence-specific gene silencing
without cytotoxicity. Systemically administered uPIC-AuNPs showed appreciably
longer blood circulation time compared to controls, i.e., bare AuNPs and uPICs,
indicating that the conjugation of uPICs onto AuNP was crucial for enhancing
blood circulation time. Finally, the uPIC-AuNPs efficiently accumulated in a
subcutaneously inoculated luciferase-expressing cervical cancer (HeLa-Luc) model
and achieved significant luciferase gene silencing in the tumor tissue. These
results demonstrate the strong potential of uPIC-AuNP nanoarchitectures for
systemic siRNA delivery to solid tumors.
PMID- 25133610
TI - Mobile phones: the next step towards healthcare delivery in rural India?
AB - BACKGROUND: Given the ubiquity of mobile phones, their use to support healthcare
in the Indian context is inevitable. It is however necessary to assess end-user
perceptions regarding mobile health interventions especially in the rural Indian
context prior to its use in healthcare. This would contextualize the use of
mobile phone communication for health to 70% of the country's population that
resides in rural India. OBJECTIVES: To explore the acceptability of delivering
healthcare interventions through mobile phones among users in a village in rural
Bangalore. METHODS: This was an exploratory study of 488 mobile phone users,
residing in a village, near Bangalore city, Karnataka, South India. A pretested,
translated, interviewer-administered questionnaire was used to obtain data on
mobile phone usage patterns and acceptability of the mobile phone, as a tool for
health-related communication. The data is described using basic statistical
measures. RESULTS: The primary use of mobile phones was to make or receive phone
calls (100%). Text messaging (SMS) was used by only 70 (14%) of the respondents.
Most of the respondents, 484 (99%), were willing to receive health-related
information on their mobile phones and did not consider receiving such
information, an intrusion into their personal life. While receiving reminders for
drug adherence was acceptable to most 479 (98%) of our respondents, 424 (89%)
preferred voice calls alone to other forms of communication. Nearly all were
willing to use their mobile phones to communicate with health personnel in
emergencies and 367 (75%) were willing to consult a doctor via the phone in an
acute illness. Factors such as sex, English literacy, employment status, and
presence of chronic disease affected preferences regarding mode and content of
communication. CONCLUSION: The mobile phone, as a tool for receiving health
information and supporting healthcare through mHealth interventions was
acceptable in the rural Indian context.
PMID- 25133611
TI - Mst1 directs Myosin IIa partitioning of low and higher affinity integrins during
T cell migration.
AB - Chemokines promote T cell migration by transmitting signals that induce T cell
polarization and integrin activation and adhesion. Mst1 kinase is a key signal
mediator required for both of these processes; however, its molecular mechanism
remains unclear. Here, we present a mouse model in which Mst1 function is
disrupted by a hypomorphic mutation. Microscopic analysis of Mst1-deficient CD4 T
cells revealed a necessary role for Mst1 in controlling the localization and
activity of Myosin IIa, a molecular motor that moves along actin filaments. Using
affinity specific LFA-1 antibodies, we identified a requirement for Myosin IIa
dependent contraction in the precise spatial distribution of low and higher
affinity LFA-1 on the membrane of migrating T cells. Mst1 deficiency or Myosin
inhibition resulted in multipolar cells, difficulties in uropod detachment and
mis-localization of low affinity LFA-1. Thus, Mst1 regulates Myosin IIa dynamics
to organize high and low affinity LFA-1 to the anterior and posterior membrane
during T cell migration.
PMID- 25133612
TI - Experimental virus evolution reveals a role of plant microtubule dynamics and
TORTIFOLIA1/SPIRAL2 in RNA trafficking.
AB - The cytoskeleton is a dynamic network composed of filamentous polymers and
regulatory proteins that provide a flexible structural scaffold to the cell and
plays a fundamental role in developmental processes. Mutations that alter the
spatial orientation of the cortical microtubule (MT) array of plants are known to
cause important changes in the pattern of cell wall synthesis and developmental
phenotypes; however, the consequences of such alterations on other MT-network
associated functions in the cytoplasm are not known. In vivo observations
suggested a role of cortical MTs in the formation and movement of Tobacco mosaic
virus (TMV) RNA complexes along the endoplasmic reticulum (ER). Thus, to probe
the significance of dynamic MT behavior in the coordination of MT-network
associated functions related to TMV infection and, thus, in the formation and
transport of RNA complexes in the cytoplasm, we performed an evolution experiment
with TMV in Arabidopsis thaliana tor1/spr2 and tor2 mutants with specific defects
in MT dynamics and asked whether TMV is sensitive to these changes. We show that
the altered cytoskeleton induced genetic changes in TMV that were correlated with
efficient spread of infection in the mutant hosts. These observations demonstrate
a role of dynamic MT rearrangements and of the MT-associated protein
TORTIFOLIA1/SPIRAL2 in cellular functions related to virus spread and indicate
that MT dynamics and MT-associated proteins represent constraints for virus
evolution and adaptation. The results highlight the importance of the dynamic
plasticity of the MT network in directing cytoplasmic functions in macromolecular
assembly and trafficking and illustrate the value of experimental virus evolution
for addressing the cellular functions of dynamic, long-range order systems in
multicellular organisms.
PMID- 25133616
TI - Cautionary case: low Glasgow Coma Scale scores, brainstem involvement,
decompressive craniectomy, full recovery, and one more reason for
advocacy/collaboration.
AB - Presurgical selection criteria for decompressive craniectomy (DC) for treatment
of severe traumatic brain injury remain controversial. Proposed criteria to
improve outcomes include high admission Glasgow Coma Scale scores (>=7) and
exclusion of patients having brainstem involvement. Neurosurgeons may be unaware
of long-term functional outcomes in their DC patients. Therefore, to underscore
an exceptional outcome that may have been facilitated by DC, while highlighting
need for caution in development of potentially overly restrictive presurgical
selection criteria, this case report of a 21-yr-old premed college student
admitted with severe traumatic brain injury, Glasgow Coma Scale score of 3, left
fixed dilated pupil, and brainstem signs, who had emergency DC, is presented.
Nine years after the trauma, she was employed full time as a physician, and only
residual symptom, an occasional headache, remained. Thus, caution is necessary in
the development of DC presurgical selection guidelines, as this case had
excellent long-term functional outcome that may have been facilitated by DC
despite initial low Glasgow Coma Scale scores and signs of brainstem involvement.
Also, this case highlights one more reason for multispecialty physician advocacy,
collaboration, and comparative effectiveness research.
PMID- 25133615
TI - Barriers to early mobility of hospitalized general medicine patients: survey
development and results.
AB - OBJECTIVE: Functional status decline commonly accompanies hospitalization making
patients vulnerable to complications. Such decline can be mitigated through
hospital-based early mobility programs. Success in implementing patient mobility
quality improvement processes requires evaluating providers' knowledge,
attitudes, and behaviors. DESIGN: A cross-sectional, self-administered survey in
two different hospital settings was completed by 120 nurses and physical and
occupational therapists (rehabilitation therapists, 38; nurses, 82) from six
general medicine units. The survey was developed using published guidelines,
literature review, and provider meetings and refined through pilot testing.
Psychometric properties were assessed, and regression analyses were conducted to
examine barriers to early mobility by hospital site, provider discipline, and
years of experience. RESULTS: Internal consistency reliability, item consistency,
and discriminant validity psychometric characteristics were acceptable. In
multivariable regression analysis, overall perceived barriers were similar
between the two hospitals (P = 0.25) and significantly higher for staff with less
experience (P = 0.02) and for nurses vs. rehabilitation therapists (P <
0.001).The survey identified specific barriers common to both nurses and
rehabilitation therapists and other barriers that were discipline specific.
CONCLUSIONS: This novel survey identified important barriers to mobilizing
medical inpatients that were similar across two hospital settings. These results
can assist with the implementation of quality improvement projects for increasing
early hospital-based patient mobility.
PMID- 25133613
TI - Targeted next-generation sequencing reveals novel USH2A mutations associated with
diverse disease phenotypes: implications for clinical and molecular diagnosis.
AB - USH2A mutations have been implicated in the disease etiology of several inherited
diseases, including Usher syndrome type 2 (USH2), nonsyndromic retinitis
pigmentosa (RP), and nonsyndromic deafness. The complex genetic and phenotypic
spectrums relevant to USH2A defects make it difficult to manage patients with
such mutations. In the present study, we aim to determine the genetic etiology
and to characterize the correlated clinical phenotypes for three Chinese
pedigrees with nonsyndromic RP, one with RP sine pigmento (RPSP), and one with
USH2. Family histories and clinical details for all included patients were
reviewed. Ophthalmic examinations included best corrected visual acuities, visual
field measurements, funduscopy, and electroretinography. Targeted next-generation
sequencing (NGS) was applied using two sequence capture arrays to reveal the
disease causative mutations for each family. Genotype-phenotype correlations were
also annotated. Seven USH2A mutations, including four missense substitutions
(p.P2762A, p.G3320C, p.R3719H, and p.G4763R), two splice site variants
(c.8223+1G>A and c.8559-2T>C), and a nonsense mutation (p.Y3745*), were
identified as disease causative in the five investigated families, of which three
reported to have consanguineous marriage. Among all seven mutations, six were
novel, and one was recurrent. Two homozygous missense mutations (p.P2762A and
p.G3320C) were found in one individual family suggesting a potential double hit
effect. Significant phenotypic divergences were revealed among the five families.
Three families of the five families were affected with early, moderated, or late
onset RP, one with RPSP, and the other one with USH2. Our study expands the
genotypic and phenotypic variability relevant to USH2A mutations, which would
help with a clear insight into the complex genetic and phenotypic spectrums
relevant to USH2A defects, and is complementary for a better management of
patients with such mutations. We have also demonstrated that a targeted NGS
approach is a valuable tool for the genetic diagnosis of USH2 and RP.
PMID- 25133614
TI - Is thymidine glycol containing DNA a substrate of E. coli DNA mismatch repair
system?
AB - The DNA mismatch repair (MMR) system plays a crucial role in the prevention of
replication errors and in the correction of some oxidative damages of DNA bases.
In the present work the most abundant oxidized pyrimidine lesion, 5,6-dihydro-5,6
dihydroxythymidine (thymidine glycol, Tg) was tested for being recognized and
processed by the E. coli MMR system, namely complex of MutS, MutL and MutH
proteins. In a partially reconstituted MMR system with MutS-MutL-MutH proteins,
G/Tg and A/Tg containing plasmids failed to provoke the incision of DNA. Tg
residue in the 30-mer DNA duplex destabilized double helix due to stacking
disruption with neighboring bases. However, such local structural changes are not
important for E. coli MMR system to recognize this lesion. A lack of repair of Tg
containing DNA could be due to a failure of MutS (a first acting protein of MMR
system) to interact with modified DNA in a proper way. It was shown that Tg in
DNA does not affect on ATPase activity of MutS. On the other hand, MutS binding
affinities to DNA containing Tg in G/Tg and A/Tg pairs are lower than to DNA with
a G/T mismatch and similar to canonical DNA. Peculiarities of MutS interaction
with DNA was monitored by Forster resonance energy transfer (FRET) and
fluorescence anisotropy. Binding of MutS to Tg containing DNAs did not result in
the formation of characteristic DNA kink. Nevertheless, MutS homodimer
orientation on Tg-DNA is similar to that in the case of G/T-DNA. In contrast to
G/T-DNA, neither G/Tg- nor A/Tg-DNA was able to stimulate ADP release from MutS
better than canonical DNA. Thus, Tg residue in DNA is unlikely to be recognized
or processed by the E. coli MMR system. Probably, the MutS transformation to
active "sliding clamp" conformation on Tg-DNA is problematic.
PMID- 25133617
TI - Swallowing appliance: intraoral reshaping prosthesis for dysphagia secondary to
oral floor cancer: a pilot study.
AB - Patients with oral floor cancer often have difficulty swallowing solid foods. The
aim of this study was to improve the propulsion of solid foods using a swallowing
appliance (SW-A). Subjects comprised three patients with oral floor cancer who
had undergone curative surgery. Each participant was asked to swallow gelatin
under three conditions: without an SW-A, with a maxillary SW-A, and with both
maxillary and mandibular SW-As. This procedure was repeated thrice with three
volumes of gelatin (2.5, 5, and 7.5 ml), with videofluorographic swallowing
study. Swallowing was assessed on the basis of whether the participant could
propel the gelatin from the oral cavity to the pharynx. No subject could propel
2.5 ml of gelatin to the pharynx without an SW-A or with only a maxillary SW-A in
place. When both SW-As were used, all subjects could propel all three volumes of
gelatin. The mandibular SW-A complemented the compensatory effects of the
maxillary SW-A.
PMID- 25133618
TI - Affective state and community integration after traumatic brain injury.
AB - Previous studies investigating the relationship between affective state and
community integration have focused primarily on the influence of depression and
anxiety. In addition, they have focused on frequency of participation in various
activities, failing to address an individual's subjective satisfaction with
participation. The purpose of this study was to examine how affective state
contributes to frequency of participation and satisfaction with participation
after traumatic brain injury among participants with and without a current major
depressive episode. Sixty-four community-dwelling participants with a history of
complicated mild-to-severe traumatic brain injury participated in this cross
sectional cohort study. High positive affect contributed significantly to
frequency of participation (beta = 0.401, P = 0.001), and both high positive
affect and low negative affect significantly contributed to better satisfaction
with participation (F2,61 = 13.63, P < 0.001). Further investigation to assess
the direction of these relationships may better inform effective targets for
intervention. These findings highlight the importance of assessing affective
state after traumatic brain injury and incorporating a subjective measure of
participation when considering community integration outcomes.
PMID- 25133619
TI - Pneumocephalus during cervical transforaminal epidural steroid injections: a case
report.
AB - A cervical transforaminal epidural injection of anesthetic and corticosteroids
(CTFESI) is a frequently used procedure for cervical radiculopathy. Most cases of
pneumocephalus after an epidural block occur when using an interlaminar approach
with the loss-of-resistance technique. The authors present the first case of
pneumocephalus after cervical transforaminal epidural injection of anesthetic and
corticosteroids. A 64-yr-old woman with left C7 radiculopathy was undergoing C6-7
transforaminal epidural injection of anesthetic and corticosteroids. The epidural
spread of contrast was checked by fluoroscope, and 5 mg of dexamethasone in 4 ml
of 0.1875% ropivacaine was injected. She lost consciousness 5 mins after the
procedure and regained awareness after manual ventilation. She subsequently
complained of nausea and headache, and a computed tomography brain scan revealed
pneumocephalus. After carefully assessing the fluoroscopic images, the authors
believe that the needle may have punctured the dura mater of the nerve root
sleeve, allowing air to enter the subdural space. Thus, fluoroscopic images
should be carefully examined to reduce dural puncture when performing cervical
transforaminal epidural injection of anesthetic and corticosteroids, and air
should be completely removed from the needle, extension tube, and syringe.
PMID- 25133620
TI - Clinical tests of ankle plantarflexor strength do not predict ankle power
generation during walking.
AB - OBJECTIVE: The aim of this study was to investigate the relationship between a
clinical test of ankle plantarflexor strength and ankle power generation (APG) at
push-off during walking. DESIGN: This is a prospective cross-sectional study of
102 patients with traumatic brain injury. OUTCOME MEASURES: Handheld dynamometry
was used to measure ankle plantarflexor strength. Three-dimensional gait analysis
was performed to quantify ankle power generation at push-off during walking.
RESULTS: Ankle plantarflexor strength was only moderately correlated with ankle
power generation at push-off (r = 0.43, P < 0.001; 95% confidence interval, 0.26
0.58). There was also a moderate correlation between ankle plantarflexor strength
and self-selected walking velocity (r = 0.32, P = 0.002; 95% confidence interval,
0.13-0.48). CONCLUSIONS: Handheld dynamometry measures of ankle plantarflexor
strength are only moderately correlated with ankle power generation during
walking. This clinical test of ankle plantarflexor strength is a poor predictor
of calf muscle function during gait in people with traumatic brain injury.
PMID- 25133621
TI - Congenital agenesis of the superficial posterior compartment calf muscles in a 13
month-old infant.
AB - Muscle agenesis may induce cosmetic and functional deficits, particularly if the
muscle is an axial limb or a large muscle. Limb muscle agenesis is a rare
condition. Here, the authors report the case of a 13-mo-old girl with unilateral
atrophic calf and gait abnormality. Magnetic resonance imaging confirmed agenesis
of the posterior superficial compartment of the calf. The patient showed an out
toeing calcaneal gait and fibular length discrepancy secondarily during growth.
Normal embryology and the differential diagnostic point of foot deformity as well
as the clinical implications of calf agenesis are described.
PMID- 25133622
TI - Gluteus maximus calcific tendonosis: a rare cause of sciatic pain.
AB - Extraspinal causes of radicular pain are rare and are in danger of being
overlooked. Here, we present a patient with pain radiating into the posterior
thigh and lateral calf. Although initial differential diagnosis included lumbar
herniated nucleus pulposus, further imaging revealed the presence of gluteus
maximus calcific tendonosis. After physical therapy and a potent oral steroid
regimen, the pain gradually resolved and the patient was able to return to full
activity.
PMID- 25133625
TI - Myasthenis gravis or Lambert-Eaton myasthenic syndrome?
PMID- 25133624
TI - Targeted rehabilitation after extracellular matrix scaffold transplantation for
the treatment of volumetric muscle loss.
AB - Rehabilitation therapy is an important aspect of recovery after volumetric muscle
loss. However, the traditional rehabilitation approach involves a period of rest
and passive loading followed by gradual active loading. Extracellular matrix is a
naturally occurring material consisting of structural proteins that provide
mechanical strength, structural support, and functional molecules with diverse
bioactive properties. There is evidence to suggest that the addition of
aggressive regenerative rehabilitation protocols immediately after surgical
implantation of an extracellular matrix scaffold to an area of volumetric muscle
loss has significant benefits for extracellular matrix remodeling. Rehabilitation
exercises likely provide the needed mechanical signals to encourage cell
migration and site-specific differentiation in the temporal framework required
for constructive remodeling. Herein, the authors review the literature and
present an example of an aggressive rehabilitation program implemented
immediately after extracellular matrix transplantation into a severely injured
quadriceps muscle.
PMID- 25133623
TI - Allogeneic Articular Chondrocyte Transplantation Downregulates Interleukin 8 Gene
Expression in the Degenerating Rabbit Intervertebral Disk In Vivo.
AB - OBJECTIVE: The aim of this study was to investigate whether repopulating the
degenerating intervertebral disk (IVD) with articular chondrocytes will decrease
inflammation in the degenerating rabbit IVD. DESIGN: This was a biologic study in
a rabbit IVD-injury model in vivo. Dual cell tracking methods (infrared dye
labeling and adenovirus transduction) were used to demonstrate the viability of
allogeneic articular chondrocytes injected into degenerating rabbit IVDs.
Interleukin 8 gene expression was determined via real-time polymerase chain
reaction. Infiltrating inflammatory cells (macrophages, T cells, or neutrophils)
were examined with immunohistochemistry. The IVDs were also examined by routine
histology. RESULTS: Articular chondrocytes labeled with infrared dye were
detected in the degenerating IVDs at both 2 and 8 wks after injection. At the 2
wk time point, interleukin 8 gene expression was comparable in IVDs injected with
chondrocytes and in intact disks as control (P = 0.647), whereas its expression
in IVDs injected with saline increased 50-fold (P = 0.028). Transgene expression
of red fluorescent protein, beta-galactosidase, and human bone morphogenetic
protein 7 diminished at 8 wks after injection. IVDs injected with chondrocytes
overexpressing human bone morphogenetic protein 7 did not show lower interleukin
8 gene expression or improved histology. Macrophages were consistently detected
by immunohistochemistry in the cartilage formed around the needle insertion sites
in both the saline and chondrocyte groups, whereas neither T cells nor
neutrophils were detected. CONCLUSIONS: Allogeneic rabbit articular chondrocyte
survived in the degenerating rabbit IVDs for at least 8 wks. Cell treatment
resulted in reduced IVD inflammation but did not significantly improve IVD
structure.
PMID- 25133628
TI - Fluoride free synthesis of anatase TiO2 nanocrystals with exposed active {001}
facets.
AB - A novel fluoride free protocol for highly truncated anatase TiO2 nanocrystals
with exposed {001} facets by preferential adsorption of CO3(2-) ions is
developed. Experimental observations were corroborated by first principle quantum
chemical DFT calculations. The synthesized anatase TiO2 showed improved
photocatalytic activity.
PMID- 25133626
TI - Hope for successful implementation of psychosocial/psychiatric rehabilitation in
the forensic mental health setting.
AB - OBJECTIVE: To explore staff perceptions of the successes and barriers to
implementation of the psychosocial/psychiatric rehabilitation (PSR) model in the
forensic mental health setting and identify staff supports needed for greater
implementation. METHOD: A qualitative descriptive design was used and staff focus
group data was analyzed using the constant comparative method. RESULTS: All
aspects of PSR are being implemented in the forensic setting. Barriers limiting
comprehensive implementation include hospital processes and functions, legal
components, client clinical presentation, staff attributes and interactions, and
lack of resources. To foster greater implementation, employees require support to
improve interprofessional interactions and acquire additional resources and
education. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Strengthening existing
successes and addressing barriers identified will foster greater PSR
implementation in the forensic setting. Adjusting the physical environment,
streamlining documentation, shifting focus from security to rehabilitation goals,
and adapting PSR principles to various levels of illness acuity and stages of
treatment would enhance PSR implementation. A management focus on improving staff
morale, self-care, peer support, team cohesion, and communication would limit
burnout and increase successful implementation of PSR. Additional educational
opportunities and ongoing training are suggested to support a unified
understanding and sustained approach to PSR implementation in the forensic
setting.
PMID- 25133627
TI - Nuclear translocation of hARD1 contributes to proper cell cycle progression.
AB - Arrest defective 1 (ARD1) is an acetyltransferase that is highly conserved across
organisms, from yeasts to humans. The high homology and widespread expression of
ARD1 across multiple species and tissues signify that it serves a fundamental
role in cells. Human ARD1 (hARD1) has been suggested to be involved in diverse
biological processes, and its role in cell proliferation and cancer development
has been recently drawing attention. However, the subcellular localization of
ARD1 and its relevance to cellular function remain largely unknown. Here, we have
demonstrated that hARD1 is imported to the nuclei of proliferating cells,
especially during S phase. Nuclear localization signal (NLS)-deleted hARD1
(hARD1DeltaN), which can no longer access the nucleus, resulted in cell
morphology changes and cellular growth impairment. Notably, hARD1DeltaN
expressing cells showed alterations in the cell cycle and the expression levels
of cell cycle regulators compared to hARD1 wild-type cells. Furthermore, these
effects were rescued when the nuclear import of hARD1 was restored by exogenous
NLS. Our results show that hARD1 nuclear translocation mediated by NLS is
required for cell cycle progression, thereby contributing to proper cell
proliferation.
PMID- 25133629
TI - The cybotactic nematic phase of bent-core mesogens: state of the art and future
developments.
AB - The molecular clustering observed in the fluid nematic phase of nonlinear liquid
crystal molecules underlies exaggerated field effects that portend unique
technological advances in next-generation liquid crystal displays. However, the
detailed nature of the molecular organization within the clusters and the
temporal and spatial persistence of the organization remain unclear. Herein we
review the evolution of structural studies of this unique nematic phase. The
mounting experimental evidence points to a converging picture of the microscopic
nature of this relatively new class of liquid crystals.
PMID- 25133631
TI - Region-specific sensitivity of anemophilous pollen deposition to temperature and
precipitation.
AB - Understanding relations between climate and pollen production is important for
several societal and ecological challenges, importantly pollen forecasting for
pollinosis treatment, forensic studies, global change biology, and high
resolution palaeoecological studies of past vegetation and climate fluctuations.
For these purposes, we investigate the role of climate variables on annual-scale
variations in pollen influx, test the regional consistency of observed patterns,
and evaluate the potential to reconstruct high-frequency signals from sediment
archives. A 43-year pollen-trap record from the Netherlands is used to
investigate relations between annual pollen influx, climate variables (monthly
and seasonal temperature and precipitation values), and the North Atlantic
Oscillation climate index. Spearman rank correlation analysis shows that
specifically in Alnus, Betula, Corylus, Fraxinus, Quercus and Plantago both
temperature in the year prior to (T-1), as well as in the growing season (T), are
highly significant factors (TApril rs between 0.30 [P<0.05[ and 0.58 [P<0.0001];
TJuli-1 rs between 0.32 [P<0.05[ and 0.56 [P<0.0001]) in the annual pollen influx
of wind-pollinated plants. Total annual pollen prediction models based on
multiple climate variables yield R2 between 0.38 and 0.62 (P<0.0001). The effect
of precipitation is minimal. A second trapping station in the SE Netherlands,
shows consistent trends and annual variability, suggesting the climate factors
are regionally relevant. Summer temperature is thought to influence the formation
of reproductive structures, while temperature during the flowering season
influences pollen release. This study provides a first predictive model for
seasonal pollen forecasting, and also aides forensic studies. Furthermore,
variations in pollen accumulation rates from a sub-fossil peat deposit are
comparable with the pollen trap data. This suggests that high frequency
variability pollen records from natural archives reflect annual past climate
variability, and can be used in palaeoecological and -climatological studies to
bridge between population- and species-scale responses to climate forcing.
PMID- 25133630
TI - Evaluation of antimalarial activity and toxicity of a new primaquine prodrug.
AB - Plasmodium vivax is the most prevalent of the five species causing malaria in
humans. The current available treatment for P. vivax malaria is limited and
unsatisfactory due to at least two drawbacks: the undesirable side effects of
primaquine (PQ) and drug resistance to chloroquine. Phenylalanine-alanine-PQ (Phe
Ala-PQ) is a PQ prodrug with a more favorable pharmacokinetic profile compared to
PQ. The toxicity of this prodrug was evaluated in in vitro assays using a human
hepatoma cell line (HepG2), a monkey kidney cell line (BGM), and human red blood
cells deficient in the enzyme glucose-6-phosphate-dehydrogenase (G6PD). In
addition, in vivo toxicity assays were performed with rats that received multiple
doses of Phe-Ala-PQ to evaluate biochemical, hematological, and histopathological
parameters. The activity was assessed by the inhibition of the sporogonic cycle
using a chicken malaria parasite. Phe-Ala-PQ blocked malaria transmission in
Aedes mosquitoes. When compared with PQ, it was less cytotoxic to BGM and HepG2
cells and caused less hemolysis of G6PD-deficient red blood cells at similar
concentrations. The prodrug caused less alteration in the biochemical parameters
than did PQ. Histopathological analysis of the liver and kidney did show
differences between the control and Phe-Ala-PQ-treated groups, but they were not
statistically significant. Taken together, the results highlight the prodrug as a
novel lead compound candidate for the treatment of P. vivax malaria and as a
blocker of malaria transmission.
PMID- 25133634
TI - De novo design of self-assembled hexapeptides as beta-amyloid (Abeta) peptide
inhibitors.
AB - The ability of peptides to construct specific secondary structures provides a
useful function for biomaterial design that cannot be achieved with traditional
organic molecules and polymers. Inhibition of amyloid formation is a promising
therapeutic approach for the treatment of neurodegenerative diseases. Existing
peptide-based inhibitors are mainly derived from original amyloid sequences,
which have very limited sequence diversity and activity. It is highly desirable
to explore other peptide-based inhibitors that are not directly derived from
amyloid sequences. Here, we develop a hybrid high-throughput computational method
to efficiently screen and design hexapeptide inhibitors against amyloid-beta
(Abeta) aggregation and toxicity from the first principle. Computationally
screened/designed inhibitors are then validated for their inhibition activity
using biophysical experiments. We propose and demonstrate a proof-of-concept of
the "like-interacts-like" design principle that the self-assembling peptides are
able to interact strongly with conformationally similar motifs of Abeta peptides
and to competitively reduce Abeta-Abeta interactions, thus preventing Abeta
aggregation and Abeta-induced toxicity. Such a de novo design can also be
generally applicable to design new peptide inhibitors against other amyloid
diseases, beyond traditional peptide inhibitors with homologous sequences to
parent amyloid peptides.
PMID- 25133632
TI - A conserved cysteine residue of Bacillus subtilis SpoIIIJ is important for
endospore development.
AB - During sporulation in Bacillus subtilis, the onset of activity of the late
forespore-specific sigma factor sigmaG coincides with completion of forespore
engulfment by the mother cell. At this stage, the forespore becomes a free
protoplast, surrounded by the mother cell cytoplasm and separated from it by two
membranes that derive from the asymmetric division septum. Continued gene
expression in the forespore, isolated from the surrounding medium, relies on the
SpoIIIA-SpoIIQ secretion system assembled from proteins synthesised both in the
mother cell and in the forespore. The membrane protein insertase SpoIIIJ, of the
YidC/Oxa1/Alb3 family, is involved in the assembly of the SpoIIIA-SpoIIQ complex.
Here we show that SpoIIIJ exists as a mixture of monomers and dimers stabilised
by a disulphide bond. We show that residue Cys134 within transmembrane segment 2
(TM2) of SpoIIIJ is important to stabilise the protein in the dimeric form.
Labelling of Cys134 with a Cys-reactive reagent could only be achieved under
stringent conditions, suggesting a tight association at least in part through
TM2, between monomers in the membrane. Substitution of Cys134 by an Ala results
in accumulation of the monomer, and reduces SpoIIIJ function in vivo. Therefore,
SpoIIIJ activity in vivo appears to require dimer formation.
PMID- 25133637
TI - Genome-wide association studies and heritability estimates of body mass index
related phenotypes in Bangladeshi adults.
AB - Many health outcomes are influenced by a person's body mass index, as well as by
the trajectory of body mass index through a lifetime. Although previous research
has established that body mass index related traits are influenced by genetics,
the relationship between these traits and genetics has not been well
characterized in people of South Asian ancestry. To begin to characterize this
relationship, we analyzed the association between common genetic variation and
five phenotypes related to body mass index in a population-based sample of 5,354
Bangladeshi adults. We discovered a significant association between SNV rs347313
(intron of NOS1AP) and change in body mass index in women over two years. In a
linear mixed-model, the G allele was associated with an increase of 0.25 kg/m2 in
body mass index over two years (p-value of 2.3.10-8). We also estimated the
heritability of these phenotypes from our genotype data. We found significant
estimates of heritability for all of the body mass index-related phenotypes. Our
study evaluated the genetic determinants of body mass index related phenotypes
for the first time in South Asians. The results suggest that these phenotypes are
heritable and some of this heritability is driven by variation that differs from
those previously reported. We also provide evidence that the genetic etiology of
body mass index related traits may differ by ancestry, sex, and environment, and
consequently that these factors should be considered when assessing the genetic
determinants of the risk of body mass index-related disease.
PMID- 25133638
TI - Assessment of species diversity and distribution of an ancient diatom lineage
using a DNA metabarcoding approach.
AB - BACKGROUND: Continuous efforts to estimate actual diversity and to trace the
species distribution and ranges in the natural environments have gone in equal
pace with advancements of the technologies in the study of microbial species
diversity from microscopic observations to DNA-based barcoding. DNA metabarcoding
based on Next Generation Sequencing (NGS) constitutes the latest advancement in
these efforts. Here we use NGS data from different sites to investigate the
geographic range of six species of the diatom family Leptocylindraceae and to
identify possible new taxa within the family. METHODOLOGY/PRINCIPAL FINDINGS: We
analysed the V4 and V9 regions of the nuclear-encoded SSU rDNA gene region in the
NGS database of the European ERA-Biodiversa project BioMarKs, collected in
plankton and sediments at six coastal sites in European coastal waters, as well
as environmental sequences from the NCBI database. All species known in the
family Leptocylindraceae were detected in both datasets, but the much larger
Illumina V9 dataset showed a higher species coverage at the various sites than
the 454 V4 dataset. Sequences identical or similar to the references of
Leptocylindrus aporus, L. convexus, L. danicus/hargravesii and Tenuicylindrus
belgicus were found in the Mediterranean Sea, North Atlantic Ocean and Black Sea
as well as at locations outside Europe. Instead, sequences identical or close to
that of L. minimus were found in the North Atlantic Ocean and the Black Sea but
not in the Mediterranean Sea, while sequences belonging to a yet undescribed
taxon were encountered only in Oslo Fjord and Baffin Bay.
CONCLUSIONS/SIGNIFICANCE: Identification of Leptocylindraceae species in NGS
datasets has expanded our knowledge of the species biogeographic distribution and
of the overall diversity of this diatom family. Individual species appear to be
widespread, but not all of them are found everywhere. Despite the sequencing
depth allowed by NGS and the wide geographic area covered by this study, the
diversity of this ancient diatom family appears to be low, at least at the level
of the marker used in this study.
PMID- 25133636
TI - The molecular phenotype of endocapillary proliferation: novel therapeutic targets
for IgA nephropathy.
AB - IgA nephropathy (IgAN) is a clinically and pathologically heterogeneous disease.
Endocapillary proliferation is associated with higher risk of progressive
disease, and clinical studies suggest that corticosteroids mitigate this risk.
However, corticosteroids are associated with protean cellular effects and
significant toxicity. Furthermore the precise mechanism by which they modulate
kidney injury in IgAN is not well delineated. To better understand molecular
pathways involved in the development of endocapillary proliferation and to
identify novel specific therapeutic targets, we evaluated the glomerular
transcriptome of microdissected kidney biopsies from 22 patients with IgAN.
Endocapillary proliferation was defined according to the Oxford scoring system
independently by 3 nephropathologists. We analyzed mRNA expression using
microarrays and identified transcripts differentially expressed in patients with
endocapillary proliferation compared to IgAN without endocapillary lesions. Next,
we employed both transcription factor analysis and in silico drug screening and
confirmed that the endocapillary proliferation transcriptome is significantly
enriched with pathways that can be impacted by corticosteroids. With this
approach we also identified novel therapeutic targets and bioactive small
molecules that may be considered for therapeutic trials for the treatment of
IgAN, including resveratrol and hydroquinine. In summary, we have defined the
distinct molecular profile of a pathologic phenotype associated with progressive
renal insufficiency in IgAN. Exploration of the pathways associated with
endocapillary proliferation confirms a molecular basis for the clinical
effectiveness of corticosteroids in this subgroup of IgAN, and elucidates new
therapeutic strategies for IgAN.
PMID- 25133639
TI - Believing is seeing: fixation duration predicts implicit negative attitudes.
AB - A prototypical finding of social cognition is that social experiences influence
later performance even though those experiences are not introspectively
available. Building on social cognition research on implicit attitudes, we
evaluate whether ethnic category/attribute pairs influence eye movements during
the Implicit Association Test (IAT, Greenwald, McGhee, & Schwartz 1998). Results
show that fixation duration predicted implicit attitudes such that when the
category/attribute pairs disconfirmed one's implicit negative attitude fixation
duration toward that pair increased. The present research provides evidence that
eye movements and implicit processes inherent in the IAT are more broadly
connected than previously thought.
PMID- 25133640
TI - Association between perceived social stigma against mental disorders and use of
health services for psychological distress symptoms in the older adult
population: validity of the STIG scale.
AB - OBJECTIVES: To document the reliability, construct and nomological validity of
the perceived Social Stigmatisation (STIG) scale in the older adult population.
DESIGN: Cross-sectional survey. SETTING: Primary medical health services clinics.
PARTICIPANTS: Probabilistic sample of older adults aged 65 years and over waiting
for medical services in the general medical sector (n = 1765). MEASUREMENTS:
Perceived social stigma against people with a mental health problem was measured
using the STIG scale composed of seven indicators. RESULTS: A second-order
measurement model of perceived social stigma fitted adequately the observed data.
The reliability of the STIG scale was 0.83. According to our results, 39.6% of
older adults had a significant level of perceived social stigma against people
with a mental health problem. RESULTS showed that the perception of social stigma
against mental health problems was not significantly associated with a respondent
gender and age. RESULTS also showed that the perception of social stigma against
the mental health problems was directly associated with the respondents' need for
improved mental health (b = -0.10) and indirectly associated with their use of
primary medical health services for psychological distress symptoms (b = -0.07).
CONCLUSION: RESULTS lead us to conclude that social stigma against mental
disorders perceived by older adults may limit help-seeking behaviours and
warrants greater public health and public policy attention. Also, results lead us
to conclude that physicians should pay greater attention to their patients'
attitudes against mental disorders in order to identify possible hidden mental
health problems.
PMID- 25133642
TI - The longitudinal impact of intimate partner aggression and relationship status on
women's physical health and depression symptoms.
AB - Intimate partner aggression (IPA) has many detrimental effects, particularly
among young women. The present study examined the longitudinal effects of IPA
victimization and relationship status on physical health and depression symptoms
in a sample of 375 community women between the ages of 18 and 25 years. All
variables were assessed at 4 occasions over a 12-month period (i.e., 1 assessment
every 4 months). Multilevel modeling revealed that IPA victimization had both
between- and within-person effects on women's health outcomes, and relationship
status had within-person effects when women did not report current IPA. Although
IPA was generally related to greater physical health problems and depression
symptoms, these findings varied depending on both the type of aggression
experienced (i.e., psychological vs. physical) and relationship status (i.e.,
whether participants were in the same relationship or a new relationship).
Findings suggest that IPA can be harmful to both physical and mental health,
particularly among young women who stay in abusive relationships. Results
highlight the importance of developing effective IPA intervention programs and
providing help and resources to women who are experiencing physical or
psychological IPA in their relationships.
PMID- 25133641
TI - The appropriateness of more intensive colonoscopy screening than recommended in
Medicare beneficiaries: a modeling study.
AB - IMPORTANCE: Many Medicare beneficiaries undergo more intensive colonoscopy
screening than recommended. Whether this is favorable for beneficiaries and
efficient from a societal perspective is uncertain. OBJECTIVE: To determine
whether more intensive colonoscopy screening than recommended is favorable for
Medicare beneficiaries (ie, whether it results in a net health benefit) and
whether it is efficient from a societal perspective (ie, whether the net health
benefit justifies the additional resources required). DESIGN, SETTING, AND
PARTICIPANTS: Microsimulation modeling study of 65-year-old Medicare
beneficiaries at average risk for colorectal cancer (CRC) and with an average
life expectancy who underwent a screening colonoscopy at 55 years with negative
results. INTERVENTIONS: Colonoscopy screening as recommended by guidelines (ie,
at 65 and 75 years) vs scenarios with a shorter screening interval (5 or 3
instead of 10 years) or in which screening was continued to 85 or 95 years. MAIN
OUTCOMES AND MEASURES: Quality-adjusted life-years (QALYs) gained (measure of net
health benefit); additional colonoscopies required per additional QALY gained and
additional costs per additional QALY gained (measures of efficiency). RESULTS:
Screening previously screened Medicare beneficiaries more intensively than
recommended resulted in only small increases in CRC deaths prevented and life
years gained. In comparison, the increases in colonoscopies performed and
colonoscopy-related complications experienced were large. As a result, all
scenarios of more intensive screening than recommended resulted in a loss of
QALYs, rather than a gain (ie, a net harm). The only exception was shortening the
screening interval from 10 to 5 years, which resulted in 0.7 QALYs gained per
1000 beneficiaries. However, this scenario was inefficient because it required no
less than 909 additional colonoscopies and an additional $711 000 per additional
QALY gained. Results in previously unscreened beneficiaries were slightly less
unfavorable, but conclusions were identical. CONCLUSIONS AND RELEVANCE: Screening
Medicare beneficiaries more intensively than recommended is not only inefficient
from a societal perspective; often it is also unfavorable for those being
screened. This study provides evidence and a clear rationale for clinicians and
policy makers to actively discourage this practice.
PMID- 25133643
TI - Couples and breast cancer: women's mood and partners' marital satisfaction
predicting support perception.
AB - Women who are diagnosed with breast cancer can experience an array of
psychosocial difficulties; however, social support, particularly from a spouse,
has been shown to have a protective function during this time. This study
examined the ways in which a woman's daily mood, pain, and fatigue, and her
spouse's marital satisfaction predict the woman's report of partner support in
the context of breast cancer. Pretest data from a larger intervention study and
multilevel modeling were used to examine the effects of women's daily mood, pain,
and fatigue and average levels of mood, pain, and fatigue on women's report of
social support received from her partner, as well as how the effects of mood
interacted with partners' marital satisfaction. Results show that on days in
which women reported higher levels of negative or positive mood, as well as on
days they reported more pain and fatigue, they reported receiving more support.
Women who, on average, reported higher levels of positive mood tended to report
receiving more support than those who, on average, reported lower positive mood.
However, average levels of negative mood were not associated with support. Higher
average levels of fatigue but not pain were associated with higher support.
Finally, women whose husbands reported higher levels of marital satisfaction
reported receiving more partner support, but husbands' marital satisfaction did
not moderate the effect of women's mood on support. Implications of these
findings are discussed relative to assisting couples during this difficult time
in their lives.
PMID- 25133644
TI - A randomized trial comparing time intervals from HCG trigger to intrauterine
insemination for cycles utilizing GnRH antagonists.
AB - Intrauterine insemination (IUI) during ovarian stimulation cycles is typically
performed 36 hours after human chorionic gonadotropin (hCG) injection. We
hypothesized that adjusting the time interval to IUI to better coincide with
ovulation may increase pregnancy rates. Patients undergoing induction of
ovulation utilizing gonadotropins and gonadotropin releasing hormone (GnRH)
antagonists and IUI were divided to three groups based on the time from hCG
injection to IUI: 36, 42, and 48 hours. Primary outcome was defined as the
clinical pregnancy rate. Secondary outcomes comprised additional parameters
including multifetal pregnancy rate. A total of 92 patients completed the study.
Baseline parameters were similar between the groups. The clinical pregnancy rate
in the three groups was 20%, 38%, and 24%, respectively. While the 42 hour time
interval had a higher numerical pregnancy rate, the pregnancy rates did not
differ statistically among the study groups. The multifetal pregnancy rate did
not differ among the three groups as well. A larger study is necessary to
ascertain if a 42 hour time interval can indeed improve pregnancy rates.
PMID- 25133646
TI - Effect of frequent WBC treatments on the back pain therapy in elderly men.
AB - Cryotherapy is the application of a stimulus of a cryotherapeutic temperature
below -100 degrees C in a period of 1-3 min in order to stimulate and use
physiological reactions of human body to cold. It can be applied to specific body
parts or to a whole body. Whole-body cryotherapy is a treatment method applied in
treatment of motor organ issues, nervous system diseases, psychiatry, dermatology
and laryngology. The research group consisted of 80 male in the age range of 65
77 suffering from chronic, lasting more than 3 months, lower back pain. The
subjects qualified to the research were divided into two groups. Group A
consisted of 40 patients who participated in whole-body cryotherapy (WBC) twice a
week. Group B also contained 40 patients who participated in WBC whole week.
Examinations were conducted twice. The first one was conducted before the
commencement of the treatment while the second one after the therapy was over.
The results of the research did not show any statistically significant
improvement in patients from Group A. However, the results obtained by Group B
have proven significant condition improvement and enable the researchers to
conclude that WBC is effective in treating patients with lower back pain.
PMID- 25133645
TI - The Nijmegen decision tool for chronic low back pain. Development of a clinical
decision tool for secondary or tertiary spine care specialists.
AB - BACKGROUND: In Western Europe, low back pain has the greatest burden of all
diseases. When back pain persists, different medical specialists are involved and
a lack of consensus exists among these specialists for medical decision-making in
Chronic Low Back Pain (CLBP). OBJECTIVE: To develop a decision tool for secondary
or tertiary spine care specialists to decide which patients with CLBP should be
seen by a spine surgeon or by other non-surgical medical specialists. METHODS: A
Delphi study was performed to identify indicators predicting the outcome of
interventions. In the preparatory stage evidence from international guidelines
and literature were summarized. Eligible studies were reviews and longitudinal
studies. Inclusion criteria: surgical or non-surgical interventions and
persistence of complaints, CLBP-patients aged 18-65 years, reported baseline
measures of predictive indicators, and one or more reported outcomes had to
assess functional status, quality of life, pain intensity, employment status or a
composite score. Subsequently, a three-round Delphi procedure, to reach consensus
on candidate indicators, was performed among a multidisciplinary panel of 29 CLBP
professionals (>five years CLBP-experience). The pre-set threshold for general
agreement was >=70%. The final indicator set was used to develop a clinical
decision tool. RESULTS: A draft list with 53 candidate indicators (38 with
conclusive evidence and 15 with inconclusive evidence) was included for the
Delphi study. Consensus was reached to include 47 indicators. A first version of
the decision tool was developed, consisting of a web-based screening
questionnaire and a provisional decision algorithm. CONCLUSIONS: This is the
first clinical decision tool based on current scientific evidence and formal
multidisciplinary consensus that helps referring the patient for consultation to
a spine surgeon or a non-surgical spine care specialist. We expect that this tool
considerably helps in clinical decision-making spine care, thereby improving
efficient use of scarce sources and the outcomes of spinal interventions.
PMID- 25133647
TI - Molecular features contributing to virus-independent intracellular localization
and dynamic behavior of the herpesvirus transport protein US9.
AB - Reaching the right destination is of vital importance for molecules, proteins,
organelles, and cargoes. Thus, intracellular traffic is continuously controlled
and regulated by several proteins taking part in the process. Viruses exploit
this machinery, and viral proteins regulating intracellular transport have been
identified as they represent valuable tools to understand and possibly direct
molecules targeting and delivery. Deciphering the molecular features of viral
proteins contributing to (or determining) this dynamic phenotype can eventually
lead to a virus-independent approach to control cellular transport and delivery.
From this virus-independent perspective we looked at US9, a virion component of
Herpes Simplex Virus involved in anterograde transport of the virus inside
neurons of the infected host. As the natural cargo of US9-related vesicles is the
virus (or its parts), defining its autonomous, virus-independent role in vesicles
transport represents a prerequisite to make US9 a valuable molecular tool to
study and possibly direct cellular transport. To assess the extent of this
autonomous role in vesicles transport, we analyzed US9 behavior in the absence of
viral infection. Based on our studies, Us9 behavior appears similar in different
cell types; however, as expected, the data we obtained in neurons best represent
the virus-independent properties of US9. In these primary cells, transfected US9
mostly recapitulates the behavior of US9 expressed from the viral genome.
Additionally, ablation of two major phosphorylation sites (i.e. Y32Y33 and
S34ES36) have no effect on protein incorporation on vesicles and on its
localization on both proximal and distal regions of the cells. These results
support the idea that, while US9 post-translational modification may be important
to regulate cargo loading and, consequently, virion export and delivery, no
additional viral functions are required for US9 role in intracellular transport.
PMID- 25133648
TI - Preparing for PrEP: perceptions and readiness of canadian physicians for the
implementation of HIV pre-exposure prophylaxis.
AB - Recent evidence has demonstrated the efficacy of pre-exposure prophylaxis (PrEP)
for HIV prevention, but concerns persist around its use. Little is known about
Canadian physicians' knowledge of and willingness to prescribe PrEP. We
disseminated an online survey to Canadian family, infectious disease, internal
medicine, and public health physicians between September 2012-June 2013 to
determine willingness to prescribe PrEP. Criteria for analysis were met by 86
surveys. 45.9% of participants felt "very familiar" with PrEP, 49.4% felt that
PrEP should be approved by Health Canada, and 45.4% of respondents were willing
to prescribe PrEP. Self-identifying as an HIV expert (odds ratio, OR = 4.1, 95%
confidence interval, CI = 1.6-10.2), familiarity with PrEP (OR = 5.0, 95%CI = 1.3
19.0) and having been asked by patients about PrEP (OR = 4.0, 95%CI = 1.5-10.5)
were positively associated with willingness to prescribe PrEP on univariable
analysis. The latter two were the strongest predictors on multivariate analysis.
Participants cited cost and efficacy as major concerns. 75.3% did not feel that
information had been adequately disseminated among physicians. In summary,
Canadian physicians demonstrate varying levels of support for PrEP and express
concerns about its implementation. Further research on real-world effectiveness,
continuing medical education, and clinical support is needed to prepare
physicians for this prevention strategy.
PMID- 25133649
TI - Potential therapeutic utility of mesenchymal stem cells in inflammatory bowel
disease in mice.
AB - Mesenchymal stem cells (MSCs) were found to provide an effective therapeutic role
in inflammatory diseases by modulating inflammatory responses and tissue
regeneration by their differentiation ability. The present work sought to
demonstrate the potential therapeutic use of MSCs in treating chronic
inflammatory bowel disease (IBD) in mice. A new model to induce chronic IBD based
on alternative administration periods of Dextran Sodium Sulfate (DSS) was
established. Mice were divided into 2 groups; one was treated with MSCs and the
other was treated with phosphate-buffered saline (PBS). Assessment of therapeutic
efficacy of MSCs was by measuring weight, stool scoring, histopathological
examination, and measuring the gene expression of inflammatory markers:
Interleukin-23 (IL-23), Tumor necrosis factor-alpha (TNF-alpha), Interferon-gamma
(IFN-gamma), and Intercellular adhesion molecule-1 (ICAM-1). The results showed
that DSS administration causes bloody and watery stool, weight loss, and altered
histopathologic picture. MSC treated mice showed a significant improvement in
stool condition, weight gain, and normal histopathologic picture compared to the
PBS treated mice. Moreover, gene expressions of inflammatory markers in the
intestines of the MSC treated mice were also significantly lower than those of
the PBS treated mice. In conclusion, the data here showed that MSCs have a clear
potential efficacy in the treatment for IBD, as their immune modulation effects
include inhibition in the expression of key inflammatory markers that each plays
an important role in the pathogenesis of IBD.
PMID- 25133650
TI - Ketamine inhibits LPS-induced HGMB1 release in vitro and in vivo.
AB - High mobility group box 1 (HMGB1) has been identified to be a critical mediator
of severe sepsis. Ketamine has been shown to reduce sepsis-induced pathological
complications. These effects are because of the reduced expression and release of
several inflammatory mediators. However, whether ketamine affects the expression
and release of HMGB1 is not known. We investigated the effect of ketamine on
HMGB1 release in lipopolysaccharide (LPS)-induced macrophages in vitro and in
cecal ligation and puncture (CLP)-induced septic rats in vivo, and determined its
molecular mechanism of action. RAW264.7 cells or primary macrophages were
incubated with or without LPS (500 ng/mL) in the presence or absence of ketamine,
a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor (SB203580), a nuclear
factor-kappa B (NF-kappaB) inhibitor (pyrimidine dithiocarbamate), or small
interfering RNA. The protein and expression levels of inflammatory mediators,
such as HMGB1, tumor necrosis factor-alpha, and interleukin-1beta were measured
using enzyme-linked immunosorbent assays and real-time polymerase chain reaction.
The effect of ketamine on NF-kappaB and p38 MAPK activation was evaluated using
enzyme-linked immunosorbent assays, Western blot analysis, and electrophoretic
mobility shift assay. Western blotting was used to observe changes in
translocation of HMGB1 from the nucleus to cytoplasm. In addition, CLP-induced
septic rats were treated with ketamine (0.5, 5, 10 mg/kg) or saline (10 mL/kg) 3h
after sepsis, and the levels of HMGB1 and functional parameters of multiple
organs were determined using several detection kits. Seven-day survival was also
assessed. Ketamine inhibited HMGB1 release in LPS-activated RAW264.7 cells and
CLP-induced septic rats. Translocation of HMGB1 from the nucleus to cytosol and
expression of HMGB1 mRNA were inhibited significantly by ketamine. Ketamine
inhibited the translocation of NF-kappaB from the cytoplasm to the nucleus and
phosphorylation of p38 MAPK in LPS-activated RAW264.7 cells. Rats treated with
ketamine improved survival in rats and significantly reduced CLP-induced
dysfunction/injury of organs. Ketamine suppresses LPS-induced HMGB1 release in
LPS-activated RAW264.7 cells and a CLP-induced model of sepsis in rats by
partially inhibiting NF-kappaB/p38 MAPK pathways. Ketamine increased survival
time induced by CLP and reduced organ dysfunction in septic peritonitis.
PMID- 25133651
TI - Walking for Transportation and Leisure Among U.S. Adults--National Health
Interview Survey 2010.
AB - BACKGROUND: Walking, the most commonly reported physical activity among U.S.
adults, is undertaken in various domains, including transportation and leisure.
METHODS: This study examined prevalence, bout length, and mean amount of walking
in the last week for transportation and leisure, by selected characteristics.
Self-reported data from the 2010 National Health Interview Survey (N = 24,017)
were analyzed. RESULTS: Prevalence of transportation walking was 29.4% (95% CI:
28.6%-30.3%) and of leisure walking was 50.0% (95% CI: 49.1%-51.0%). Prevalence
of transportation walking was higher among men; prevalence of leisure walking was
higher among women. Most (52.4%) transportation walking bouts were 10 to 15
minutes; leisure walking bouts were distributed more evenly (28.0%, 10-15
minutes; 17.1%, 41-60 minutes). Mean time spent in transportation walking was
higher among men, decreased with increasing BMI, and varied by race/ethnicity and
region of residence. Mean time spent leisure walking increased with increasing
age and with decreasing BMI. CONCLUSION: Demographic correlates and patterns of
walking differ by domain. Interventions focusing on either leisure or
transportation walking should consider correlates for the specific walking
domain. Assessing prevalence, bout length, and mean time of walking for
transportation and leisure separately allows for more comprehensive surveillance
of walking.
PMID- 25133652
TI - Phase separation of aqueous poly(2-dimethylaminoethyl methacrylate-block-N
vinylcaprolactams).
AB - Details of the phase separation of the poly(N-vinylcaprolactam) (PVCL)
homopolymers and block copolymers of PVCL and poly(2-dimethylaminoethyl
methacrylate) (PDMAEMA) were studied in aqueous buffer solutions. Phase
separation occurred at either one or two temperatures depending on pH. The lower
critical solution temperature of PVCL can be fine-tuned by varying the molecular
weight of the block, whereas the phase separation temperature of the PDMAEMA
block is strongly dependent on pH. The enthalpies of the collapse of the PVCL
homopolymer and PVCL-b-PDMAEMA block copolymers were measured and show that the
blocks phase separate independently upon heating. PVCL is known to bind
amphiphilic cations, and correspondingly, according to light scattering, the
block copolymers dissolve as single molecules but also form aggregates at room
temperature. At temperatures above the cloud points of both blocks, only
homogeneous large aggregates were observed. Zeta potential measurements confirmed
that, upon heating, PDMAEMA blocks turn out from the collapsed PVCL globule
toward the aqueous phase.
PMID- 25133653
TI - Acid-reducing agents in infants and children: friend or foe?
PMID- 25133656
TI - Comparative analysis of risky behaviors of electric bicycles at signalized
intersections.
AB - OBJECTIVE: The primary objective of this study was to compare the risky behaviors
of e-bike, e-scooter, and bicycle riders as they were crossing signalized
intersections. METHODS: Pearson's chi-square test was used to identify whether
there were significant differences in the risky behaviors among e-bike, e
scooter, and bicycle riders. Binary logit models were developed to evaluate how
various variables affected the behaviors of 2-wheeled vehicle riders at
signalized intersections. Field data collection was conducted at 13 signalized
intersections in 2 cities (Nanjing and Kunming) in China. RESULTS: Three
different types of risky behaviors were identified, including stop beyond the
stop line, riding in motorized lanes, and riding against traffic. Two-wheeled
vehicle riders' gender and age and traffic conditions were significantly
associated with the behaviors of 2-wheeled vehicle riders at the selected
signalized intersections. CONCLUSIONS: Compared to e-bike and bicycle riders, e
scooter riders are more likely to take risky behaviors. More specifically, they
are more likely to ride in motorized lanes and ride against traffic.
PMID- 25133655
TI - PEGylation of concanavalin A to improve its stability for an in vivo glucose
sensing assay.
AB - Competitive binding assays utilizing concanavalin A (ConA) have the potential to
be the basis of improved continuous glucose monitoring devices. However, the
efficacy and lifetime of these assays have been limited, in part, by ConA's
instability due to its thermal denaturation in the physiological environment (37
degrees C, pH 7.4, 0.15 M NaCl) and its electrostatic interaction with charged
molecules or surfaces. These undesirable interactions change the constitution of
the assay and the kinetics of its behavior over time, resulting in an unstable
glucose response. In this work, poly(ethylene glycol) (PEG) chains are covalently
attached to lysine groups on the surface of ConA (i.e., PEGylation) in an attempt
to improve its stability in these environments. Dynamic light scattering
measurements indicate that PEGylation significantly improved ConA's thermal
stability at 37 degrees C, remaining stable for at least 30 days. Furthermore,
after PEGylation, ConA's binding affinity to the fluorescent competing ligand
previously designed for the assay was not significantly affected and remained at
~5.4 * 10(6) M(-1) even after incubation at 37 degrees C for 30 days. Moreover,
PEGylated ConA maintained the ability to track glucose concentrations when
implemented within a competitive binding assay system. Finally, PEGylation showed
a reduction in electrostatic-induced aggregation of ConA with poly(allylamine), a
positively charged polymer, by shielding ConA's charges. These results indicate
that PEGylated ConA can overcome the instability issues from thermal denaturation
and nonspecific electrostatic binding while maintaining the required sugar
binding characteristics. Therefore, the PEGylation of ConA can overcome major
hurdles for ConA-based glucose sensing assays to be used for long-term continuous
monitoring applications in vivo.
PMID- 25133657
TI - Long-term sustainable aluminum precursor solution for highly conductive thin
films on rigid and flexible substrates.
AB - To fabricate the highly conductive Al film via a solution process, AlH3 etherates
have been a unique Al source despite their chemical instability in solvents and
thus lack of long-term sustainability. Herein, we suggest an innovative solution
process to overcome the aforementioned drawbacks in AlH3 etherates; AlH3 aminates
powder, which can be stored in low temperature surroundings and redissolved in
solvents whenever it is needed. Since refrigeration of AlH3 aminates,
AlH3{N(CH3)3}, was very effective to prevent its chemical degradation, Al film
with excellence and uniformity in electrical and mechanical properties was
successfully fabricated even by the 180-day stored AlH3{N(CH3)3} dissolved in
solvents. Moreover, the applicability of long-term stored AlH3{N(CH3)3} to
electronic devices was experimentally demonstrated by the successful operation of
LED lamps connected to the Al pattern films on glass, PET, and paper substrates.
PMID- 25133658
TI - Accessing 2,1-borazaronaphthols: self-arylation of 1-alkyl-2-aryl-3-bromo-2,1
borazaronaphthalenes.
AB - Unlike their B-alkyl counterparts, brominated N-alkyl B-aryl 2,1
borazaronaphthalenes undergo a self-arylation reaction in the presence of a
catalytic amount of palladium and base, in which the azaborine serves as both the
electrophile and the nucleophile. The products of the self-arylation are air- and
moisture-stable 2,1-borazaronaphthols, previously only observed in basic
alcoholic solvents. The steric encumbrance of the azaborine appears to prevent
formation of the corresponding boron acid anhydride, allowing access to a family
of 2,1-borazaronaphthol derivatives.
PMID- 25133660
TI - Cancer screening in older persons: a new age of wonder.
PMID- 25133659
TI - Peer victimization and peer rejection during early childhood.
AB - The development and course of the subtypes of peer victimization is a relatively
understudied topic despite the association of victimization with important
developmental and clinical outcomes. Moreover, understanding potential
predictors, such as peer rejection and emotion regulation, in early childhood may
be especially important to elucidate possible bidirectional pathways between
relational and physical victimization and rejection. The current study (N = 97)
was designed to explore several gaps and limitations in the peer victimization
and peer rejection literature. In particular, the prospective associations
between relational and physical victimization and peer rejection over the course
of 3.5 months during early childhood (i.e., 3 to 5 years old) were investigated
in an integrated model. The study consisted of 97 (42 girls) preschool children
recruited from four early childhood schools in the northeast of the United
States. Using observations, research assistant report, and teacher report,
relational and physical aggression, relational and physical victimization, peer
rejection, and emotion regulation were measured in a short-term longitudinal
study. Path analyses were conducted to test the overall hypothesized model. Peer
rejection was found to predict increases in relational victimization. In
addition, emotion regulation was found to predict decreases in peer rejection and
physical victimization. Implications for research and practice are discussed,
including teaching coping strategies for peer rejection and emotional distress.
PMID- 25133661
TI - Increasing external effects negate local efforts to control ozone air pollution:
a case study of Hong Kong and implications for other Chinese cities.
AB - It is challenging to reduce ground-level ozone (O3) pollution at a given locale,
due in part to the contributions of both local and distant sources. We present
direct evidence that the increasing regional effects have negated local control
efforts for O3 pollution in Hong Kong over the past decade, by analyzing the
daily maximum 8 h average O3 and Ox (=O3+NO2) concentrations observed during the
high O3 season (September-November) at Air Quality Monitoring Stations. The
locally produced Ox showed a statistically significant decreasing trend over 2002
2013 in Hong Kong. Analysis by an observation-based model confirms this decline
in in situ Ox production, which is attributable to a reduction in aromatic
hydrocarbons. However, the regional background Ox transported into Hong Kong has
increased more significantly during the same period, reflecting contributions
from southern/eastern China. The combined result is a rise in O3 and a
nondecrease in Ox. This study highlights the urgent need for close cross-boundary
cooperation to mitigate the O3 problem in Hong Kong. China's air pollution
control policy applies primarily to its large cities, with little attention to
developing areas elsewhere. The experience of Hong Kong suggests that this
control policy does not effectively address secondary pollution, and that a
coordinated multiregional program is required.
PMID- 25133663
TI - The incorporation of low-substituted hydroxypropyl cellulose into solid
dispersion systems.
AB - While the use of amorphous solid dispersions to improve aqueous solubility is
well documented, little consideration has traditionally been given to the
finished dosage form. The objective of this study was to evaluate the dissolution
performance of amorphous solid dispersions containing a dispersed
superdisintegrant with binding properties. KinetiSol(r) dispersing was used to
thermally process hypromellose acetate succinate-based compositions containing
the drug substance nifedipine (NIF) and a highly compressible grade of low
substituted hydroxypropyl cellulose (New Binder Disintegrants; NBD-grade). Solid
state analysis demonstrated that compositions were rendered amorphous during
processing. Tablets containing intra-dispersion NBD were found to exhibit non
sink dissolution performance similar to milled intermediate, demonstrating
excellent disintegration characteristics. Conversely, tablets without intra
dispersion NBD were found to release significantly less NIF during dissolution
analysis due to particle agglomeration. It was determined that compressibility
and particle wetting increased as the level of intra-dispersion NBD increased.
PMID- 25133662
TI - The effects of obesity and mobility disability in access to breast and cervical
cancer screening in france: results from the national health and disability
survey.
AB - OBJECTIVES: We aimed to disentangle the effects of obesity and mobility
limitation on cervical and breast cancer screening among community dwelling
women. METHODS: The data source was the French national Health and Disability
Survey - Household Section, 2008. The Body Mass Index (BMI) was used to
categorize obesity status. We constructed a continuous score of mobility
limitations to assess the severity of disability (Cronbach's alpha = 0.84).
Logistic regressions were performed to examine the association between obesity,
mobility limitations and the use of Pap test (n = 8 133) and the use of
mammography (n = 7 561). Adjusted odds ratios were calculated (AOR). Interaction
terms between obesity and the disability score were included in models testing
for effect modifications. RESULTS: Compared with non-obese women, the odds of
having a Pap test in the past 3 years was 24% lower in obese women (AOR = 0.76;
95% CI: 0.65 to 0.89), the odds of having a mammogram in the past 2 years was 23%
lower (AOR = 0.77; 95% CI: 0.66 to 0.91). Each time the disability score was 5
points higher, the odds of having a Pap test decreases by 20% (AOR = 0.96; 95%
CI: 0.94 to 0.98), the odds of having a mammogram decreases by 25% (AOR = 0.95;
95% CI: 0.94 to 0.97). There was no significant interaction between obesity and
disability score. CONCLUSION: Obesity and mobility limitation are independently
associated with a lower likelihood of cervical and breast cancer screening.
Protective outreach and follow-up are necessary to reduce inequalities and thus
to reduce health disparities in these vulnerable and high-risk populations of
obese women with disabilities.
PMID- 25133664
TI - Increased dissolution of disulfiram by dry milling with silica nanoparticles.
AB - The purpose of this study was to find a suitable method to increase the
dissolution of disulfiram (DSF) which is easily decomposed. The dissolution of
DSF within 1 h was significantly increased from 37% to >90% by co-milling with
Aerosil(r) 200 pharm (Aerosil) and the increased dissolution remained stable
during long-term storage while there was no significant degradation of DSF. By
monitoring the changes in particle size of the grinding mixture, a mosaic DSF-in
Aerosil structure was demonstrated. The core size of the mosaic DSF/Aerosil
system was 3.625 um. The particle size of DSF was reduced from 20.75 um to ~200
nm and the size of the mosaic DSF/Aerosil system (3.625~7.956 um) increased on
increasing the drug-loading content. Differential scanning calorimetry and X-ray
powder diffraction analysis confirmed the largely amorphous state of DSF in the
mosaic drug/carrier system. Fourier transform infrared spectroscopy confirmed the
presence of hydrogen bonding between DSF and Aerosil. Scanning electron
microscopy and transmission electron microscopy verified the DSF-in-Aerosil
relationship in the particle size determination at different size levels. The
possible mechanisms of dry milling included the hypothesis that during impact and
collision, DSF particles melted into the surface of Aerosil turning them into an
amorphous state or they became inlayed into the interspaces of the Aerosil
structure with a much smaller size.
PMID- 25133666
TI - Maternal and umbilical cord copeptin levels in pregnancies complicated by fetal
growth restriction.
AB - Abstract Objective: The aim of this study was to compare maternal and fetal serum
copeptin concentrations in pregnancies complicated by isolated fetal growth
restriction (FGR), and uncomplicated pregnancies, and to investigate
relationships between copeptin levels and clinical parameters. Methods: Maternal
and fetal serum copeptin levels were measured in 21 women with pregnancies
complicated by isolated FGR and 20 women with normal pregnancies (control group).
Doppler assessment of the uterine and umbilical arteries was performed in each
patient. Results: Maternal serum copeptin levels were significantly higher in
women with isolated FGR compared to controls (p = 0.042). In addition, maternal
copeptin levels were inversely correlated with the uterine artery pulsatility and
resistance indices and positively correlated with neonatal birth weight.
Umbilical vein copeptin levels were significantly increased in neonates with
adverse outcomes (p = 0.001). Conclusions: Increased maternal copeptin
concentration may reflect a response to stress, thus serving as a compensatory
mechanism in pregnancies complicated by FGR.
PMID- 25133667
TI - Ruthenium-catalyzed allylic alkylations of chelated enolates using vinyl
dioxolanon-2-ones.
AB - 4-Vinyl-substituted 1,3-dioxolan-2-ones are found to be good substrates for Ru
catalyzed allylic alkylations of chelated amino acid ester enolates. cis-1,3
Dioxolan-2-ones are more reactive than the corresponding trans-isomers. The
attack occurs preferentially with regioretention at the position of the leaving
group with perfect chirality transfer. Therefore, this protocol is a good
complement to the Pd-catalyzed processes, which give only linear products with
this type of substrate.
PMID- 25133665
TI - Abnormal amygdala resting-state functional connectivity in adolescent depression.
AB - IMPORTANCE: Major depressive disorder (MDD) frequently emerges during adolescence
and can lead to persistent illness, disability, and suicide. The maturational
changes that take place in the brain during adolescence underscore the importance
of examining neurobiological mechanisms during this time of early illness.
However, neural mechanisms of depression in adolescents have been understudied.
Research has implicated the amygdala in emotion processing in mood disorders, and
adult depression studies have suggested amygdala-frontal connectivity deficits.
Resting-state functional magnetic resonance imaging is an advanced tool that can
be used to probe neural networks and identify brain-behavior relationships.
OBJECTIVE: To examine amygdala resting-state functional connectivity (RSFC) in
adolescents with and without MDD using resting-state functional magnetic
resonance imaging as well as how amygdala RSFC relates to a broad range of
symptom dimensions. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional resting
state functional magnetic resonance imaging study was conducted within a
depression research program at an academic medical center. Participants included
41 adolescents and young adults aged 12 to 19 years with MDD and 29 healthy
adolescents (frequency matched on age and sex) with no psychiatric diagnoses.
MAIN OUTCOMES AND MEASURES: Using a whole-brain functional connectivity approach,
we examined the correlation of spontaneous fluctuation of the blood oxygen level
dependent signal of each voxel in the whole brain with that of the amygdala.
RESULTS: Adolescents with MDD showed lower positive RSFC between the amygdala and
hippocampus, parahippocampus, and brainstem (z >2.3, corrected P < .05); this
connectivity was inversely correlated with general depression (R = -.523, P =
.01), dysphoria (R = -.455, P = .05), and lassitude (R = -.449, P = .05) and was
positively correlated with well-being (R = .470, P = .03). Patients also
demonstrated greater (positive) amygdala-precuneus RSFC (z >2.3, corrected P <
.05) in contrast to negative amygdala-precuneus RSFC in the adolescents serving
as controls. CONCLUSIONS AND RELEVANCE: Impaired amygdala-hippocampal/brainstem
and amygdala-precuneus RSFC have not previously been highlighted in depression
and may be unique to adolescent MDD. These circuits are important for different
aspects of memory and self-processing and for modulation of physiologic responses
to emotion. The findings suggest potential mechanisms underlying both mood and
vegetative symptoms, potentially via impaired processing of memories and visceral
signals that spontaneously arise during rest, contributing to the persistent
symptoms experienced by adolescents with depression.
PMID- 25133668
TI - p53-Dependent apoptosis induced in human bronchial epithelial (16-HBE) cells by
PM(2.5) sampled from air in Guangzhou, China.
AB - Epidemiological studies have shown that air pollution particulate matter (PM) is
associated with increased respiratory morbidity and mortality. However, the
mechanisms are not fully understood. Oxidative stress-mediated apoptosis plays an
important role in the occurrence of respiratory diseases. In this study, human
bronchial epithelial (16-HBE) cells were exposed to different concentrations (16
128 ug/ml) of PM(2.5) for 24 h to investigate the apoptosis induced by PM(2.5).
The results showed that PM(2.5) exposure significantly induced apoptosis, DNA
strand breaks, and oxidative damage in a dose-dependent manner in 16-HBE cells.
The expression of p53 and p73 increased significantly along with the dose of
PM(2.5) in 16-HBE cells, whereas the expression of p21(Cip1/WAF1) decreased; the
expression of mdm2 increased and then decreased, but not significantly. Taken
together, these observations indicate that PM(2.5) may lead to oxidative damage
and induce apoptosis through the p53-dependent pathway in 16-HBE cells. p53
Dependent apoptosis mediated by DNA strand breaks may be an important mechanism
of PM(2.5)-induced apoptosis in 16-HBE cells.
PMID- 25133669
TI - Coinfection with human herpesvirus 8 is associated with persistent inflammation
and immune activation in virologically suppressed HIV-infected patients.
AB - OBJECTIVES: Infection with co-pathogens is one of the postulated factors
contributing to persistent inflammation and non-AIDS events in virologically
suppressed HIV-infected patients. We aimed to investigate the relationship of
human herpesvirus-8 (HHV-8), a vasculotropic virus implicated in the pathogenesis
of Kaposi's sarcoma, with inflammation and subclinical atherosclerosis in HIV
infected patients. METHODS: Prospective study including virologically suppressed
HIV-infected patients. Several blood biomarkers (highly-sensitive C-reactive
protein [hsCRP], tumour necrosis factor-alpha, interleukin-6, monocyte
chemoattractant protein-1, vascular cell adhesion molecule-1, intercellular cell
adhesion molecule-1, malondialdehyde, plasminogen activator inhibitor [PAI-1], D
dimer, sCD14, sCD163, CD4/CD38/HLA-DR, and CD8/CD38/HLA-DR), serological tests
for HHV-8 and the majority of herpesviruses, carotid intima-media thickness, and
endothelial function through flow-mediated dilatation of the brachial artery were
measured. RESULTS: A total of 136 patients were included, 34.6% of them infected
with HHV-8. HHV-8-infected patients were more frequently co-infected with herpes
simplex virus type 2 (HSV-2) (P<0.001), and less frequently with hepatitis C
virus (HCV) (P = 0.045), and tended to be older (P = 0.086). HHV-8-infected
patients had higher levels of hsCRP (median [interquartile range], 3.63 [1.32
7.54] vs. 2.08 [0.89-4.11] mg/L, P = 0.009), CD4/CD38/HLA-DR (7.67% [4.10-11.86]%
vs. 3.86% [2.51-7.42]%, P = 0.035) and CD8/CD38/HLA-DR (8.02% [4.98-14.09]% vs.
5.02% [3.66-6.96]%, P = 0.018). After adjustment for the traditional
cardiovascular risk factors, HCV and HSV-2 infection, the associations remained
significant: adjusted difference between HHV-8 positive and negative patients
(95% confidence interval) for hsCRP, 74.19% (16.65-160.13)%; for CD4/CD38/HLA-DR,
89.65% (14.34-214.87)%; and for CD8/CD38/HLA-DR, 58.41% (12.30-123.22)%. Flow
mediated dilatation and total carotid intima-media thickness were not different
according to HHV-8 serostatus. CONCLUSION: In virologically suppressed HIV
infected patients, coinfection with HHV-8 is associated with increased
inflammation and immune activation. This might contribute to increase the risk of
non-AIDS events, including accelerated atherosclerotic disease.
PMID- 25133670
TI - The impact of visual impairment on health-related quality of life in rural
Africa.
AB - PURPOSE: To assess the impact of visual impairment (VI) on utility values in Sub
Saharan Africa and compare findings with other studies from low- and high-income
countries. METHODS: Patients with normal vision and various levels of VI were
recruited from a secondary eye clinic in rural Kenya and interviewed using time
trade-off (TTO). VI was classified using the World Health Organization definition
of (normal vision, visual acuity >=20/60, VI 20/80-20/200, severe VI 20/240
20/400, and blindness <20/400). RESULTS: Mean age of the total sample (N = 303)
was 50.3 years (standard deviation, SD, +/-18.17 years), and 51.5% of patients
were male. Most were small-scale farmers and illiteracy was high at 40%. Mean TTO
scores per group were: normal vision 0.93 (SD +/- 0.10), VI 0.88 (SD +/- 0.14),
severe VI 0.86 (SD +/- 0.13), blindness 0.73 (SD +/- 0.17; p <= 0.001). Lower TTO
scores were independently associated with worse visual acuity (p <= 0.001),
longer duration of disease (p <= 0.001) and illiteracy (p = 0.011), but not with
cause of VI, age, sex, marital status, socioeconomic status, or systemic
comorbidities in multivariate analyses. Overall, TTO scores were considerably
higher than those reported from high-income countries at similar levels of VI.
CONCLUSION: In this rural African population, duration and extent of vision loss,
rather than cause, socioeconomic factors and comorbidities affected vision
related quality of life. Our findings underline the importance of providing sight
restoring treatment as timely as possible and the necessity of enhancing
rehabilitation efforts for those with non-curable eye diseases.
PMID- 25133671
TI - Hemoglobin is associated with retinal vascular fractals in type 1 diabetes
patients.
AB - PURPOSE: Retinal vascular fractal dimension, a measure of the density of the
retinal vasculature, has been suggested as a marker of systemic microvascular
disorders in diabetes. As hemoglobin concentration is tightly related to vascular
physiology and hypoxia, the hypothesis was that hemoglobin concentration would be
associated with retinal vascular fractals in a relevant population. METHODS: In a
cross-sectional study of 204 long-term type 1 diabetes patients from a population
based cohort, retinal digital photos were captured and graded for fractal
dimension (Df) by International Retinal Imaging Software - Fractal (IRIS
Fractal). Df was calculated from a disc-centered retinal photo from the right
eye. Hemoglobin concentrations were measured using routine equipment. RESULTS: Of
175 patients with gradable images, median age was 57.7 years and median duration
of diabetes was 42 years. Median retinal Df was 1.4606 (inter-quartile range
0.0264). A positive correlation was found between hemoglobin concentration and
retinal vascular Df (r = 0.23, p = 0.0018). In a multiple linear regression
model, Df was associated with hemoglobin (coefficient 0.0054 per 1.0 mmol/L
increase in hemoglobin, p = 0.01) and age (coefficient -0.0046 for each 10-year
increase in age, p = 0.04). CONCLUSION: Hemoglobin correlated independently with
retinal vascular fractals indicating a relationship between hemoglobin
availability and retinal vascular structure.
PMID- 25133672
TI - Modifying effect of a common polymorphism in the interleukin-6 promoter on the
relationship between long-term exposure to traffic-related particulate matter and
heart rate variability.
AB - BACKGROUND: Exposure to particulate matter (PM) has been associated with an
increase in many inflammatory markers, including interleukin 6 (IL6). Air
pollution exposure has also been suggested to induce an imbalance in the
autonomic nervous system (ANS), such as a decrease in heart rate variability
(HRV). In this study we aimed to investigate the modifying effect of
polymorphisms in a major proinflammatory marker gene, interleukin 6 (IL6), on the
relationship between long-term exposure to traffic-related PM10 (TPM10) and HRV.
METHODS: For this cross-sectional study we analysed 1552 participants of the
SAPALDIA cohort aged 50 years and older. Included were persons with valid
genotype data, who underwent ambulatory 24-hr electrocardiogram monitoring, and
reported on medical history and lifestyle. Main effects of annual average TPM10
and IL6 gene variants (rs1800795; rs2069827; rs2069840; rs10242595) on HRV
indices and their interaction with average annual exposure to TPM10 were tested,
applying a multivariable mixed linear model. RESULTS: No overall association of
TPM10 on HRV was found. Carriers of two proinflammatory G-alleles of the
functional IL6 -174 G/C (rs1800795) polymorphism exhibited lower HRV. An inverse
association between a 1 ug/m3 increment in yearly averaged TPM10 and HRV was
restricted to GG genotypes at this locus with a standard deviation of normal-to
normal intervals (SDNN) (GG-carriers: -1.8%; 95% confidence interval -3.5 to
0.01; pinteraction(additive) = 0.028); and low frequency power (LF) (GG-carriers:
-5.7%; 95%CI: -10.4 to -0.8; pinteraction(dominant) = 0.049). CONCLUSIONS: Our
results are consistent with the hypothesis that traffic-related air pollution
decreases heart rate variability through inflammatory mechanisms.
PMID- 25133673
TI - Tumor bioengineering using a transglutaminase crosslinked hydrogel.
AB - Development of a physiologically relevant 3D model system for cancer research and
drug development is a current challenge. We have adopted a 3D culture system
based on a transglutaminase-crosslinked gelatin gel (Col-Tgel) to mimic the tumor
3D microenvironment. The system has several unique advantages over other
alternatives including presenting cell-matrix interaction sites from collagen
derived peptides, geometry-initiated multicellular tumor spheroids, and metabolic
gradients in the tumor microenvironment. Also it provides a controllable wide
spectrum of gel stiffness for mechanical signals, and technical compatibility
with imaging based screening due to its transparent properties. In addition, the
Col-Tgel provides a cure-in-situ delivery vehicle for tumor xenograft formation
in animals enhancing tumor cell uptake rate. Overall, this distinctive 3D system
could offer a platform to more accurately mimic in vivo situations to study tumor
formation and progression both in vitro and in vivo.
PMID- 25133675
TI - Palladium-catalyzed amination of aryl chlorides and bromides with ammonium salts.
AB - We report the palladium-catalyzed coupling of aryl halides with ammonia and
gaseous amines as their ammonium salts. The coupling of aryl chlorides and ortho
substituted aryl bromides with ammonium sulfate forms anilines with higher
selectivity for the primary arylamine over the diarylamine than couplings with
ammonia in dioxane. The resting state for the reactions of aryl chlorides is
different from the resting state for the reactions of aryl bromides, and this
change in resting states is proposed to account for a difference in selectivities
for reactions of the two haloarenes.
PMID- 25133677
TI - Lithium potential variations for metastable materials: case study of
nanocrystalline and amorphous LiFePO4.
AB - Much attention has been paid to metastable materials in the lithium battery
field, especially to nanocrystalline and amorphous materials. Nonetheless,
fundamental issues such as lithium potential variations have not been pertinently
addressed. Using LiFePO4 as a model system, we inspect such lithium potential
variations for various lithium storage modes and evaluate them thermodynamically.
The conclusions of this work are essential for an adequate understanding of the
behavior of electrode materials and even helpful in the search for new energy
materials.
PMID- 25133674
TI - A quantitative proteomic approach to identify significantly altered protein
networks in the serum of patients with lymphangioleiomyomatosis (LAM).
AB - Lymphangioleiomyomatosis (LAM) is a rare and progressive cystic lung condition
affecting approximately 3.4-7.5/million women, with an average lag time between
symptom onset and diagnosis of upwards of 4 years. The aim of this work was to
identify altered proteins in LAM serum which may be potential biomarkers of
disease. Serum from LAM patient volunteers and healthy control volunteers were
pooled and analysis carried out using quantitative 4-plex iTRAQ technology.
Differentially expressed proteins were validated using ELISAs and pathway
analysis was carried out using Ingenuity Pathway Analysis. Fourteen proteins were
differentially expressed in LAM serum compared to control serum (p<0.05). Further
screening validated the observed differences in extracellular matrix remodelling
proteins including fibronectin (30% decrease in LAM, p = 0.03), von Willebrand
Factor (40% reduction in LAM, p = 0.03) and Kallikrein III (25% increase in LAM,
p = 0.03). Pathway networks elucidated the relationships between the ECM and cell
trafficking in LAM. This study was the first to highlight an imbalance in
networks important for remodelling in LAM, providing a set of novel potential
biomarkers. These understandings may lead to a new effective treatment for LAM in
the future.
PMID- 25133676
TI - Capacity choice in a large market.
AB - We analyze endogenous capacity formation in a large frictional market with
perfectly divisible goods. Each seller posts a price and decides on a capacity.
The buyers base their decision on which seller to visit on both characteristics.
In this setting we determine the conditions for the existence and uniqueness of a
symmetric equilibrium. When capacity is unobservable there exists a continuum of
equilibria. We show that the "best" of these equilibria leads to the same seller
capacities and the same number of trades as the symmetric equilibrium under
observable capacity.
PMID- 25133678
TI - Phosphorus complexes of meso-triaryl-25-oxasmaragdyrins.
AB - The aromatic PO2 complexes of meso-triaryl-25-oxasmaragdyrins were synthesized by
treating the free base 25-oxasmaragdyrins with POCl3 in toluene/triethylamine at
refluxing temperature. The complexes are stable and characterized by X-ray and
different spectroscopic techniques. In these complexes, the phosphorus(V) ion was
bound to two pyrrolic nitrogen atoms of the smaragdyrin macrocycle and two oxygen
atoms in tetrahedral geometry. The X-ray structure revealed that the smaragdyrin
macrocycle showed significant distortion upon insertion of a PO2 unit, and the
phosphorus atom lies 1.339 A above the mean plane defined by three meso-carbon
atoms of the macrocycle. These complexes absorb strongly in the visible region
and are 2.5 times more strongly fluorescent than free base 25-oxasmaragdyrins.
The smaragdyrin macrocycle becomes electron-deficient upon complexation with a
PO2 unit because these complexes are easier to reduce but difficult to oxidize
compared to free base smaragdyrins. We designed and synthesized a covalently
linked BODIPY-PO2-smaragdyrin dyad and demonstrated efficient energy transfer
from the BODIPY unit to the PO2-smaragdyrin unit.
PMID- 25133680
TI - Oleic acid phase behavior from molecular dynamics simulations.
AB - Fatty acid aggregation is important for a number of diverse applications: from
origins of life research to industrial applications to health and disease.
Experiments have characterized the phase behavior of oleic acid mixtures, but the
molecular details are complex and hard to probe with many experiments. Coarse
grained molecular dynamics computer simulations and free energy calculations are
used to model oleic acid aggregation. From random dispersions, we observe the
aggregation of oleic acid monomers into micelles, vesicles, and oil phases,
depending on the protonation state of the oleic acid head groups. Worm-like
micelles are observed when all the oleic acid molecules are deprotonated and
negatively charged. Vesicles form spontaneously if significant amounts of both
neutral and negative oleic acid are present. Oil phases form when all the fatty
acids are protonated and neutral. This behavior qualitatively matches
experimental observations of oleic acid aggregation. To explain the observed
phase behavior, we use umbrella sampling free energy calculations to determine
the stability of individual monomers in aggregates compared to water. We find
that both neutral and negative oleic acid molecules prefer larger aggregates, but
neutral monomers prefer negatively charged aggregates and negative monomers
prefer neutral aggregates. Both neutral and negative monomers are most stable in
a DOPC bilayer, with implications on fatty acid adsorption and cellular membrane
evolution. Although the CG model qualitatively reproduces oleic acid phase
behavior, we show that an updated polarizable water model is needed to more
accurately predict the shift in pKa for oleic acid in model bilayers.
PMID- 25133682
TI - Passport officers' errors in face matching.
AB - Photo-ID is widely used in security settings, despite research showing that
viewers find it very difficult to match unfamiliar faces. Here we test
participants with specialist experience and training in the task: passport
issuing officers. First, we ask officers to compare photos to live ID-card
bearers, and observe high error rates, including 14% false acceptance of
'fraudulent' photos. Second, we compare passport officers with a set of student
participants, and find equally poor levels of accuracy in both groups. Finally,
we observe that passport officers show no performance advantage over the general
population on a standardised face-matching task. Across all tasks, we observe
very large individual differences: while average performance of passport staff
was poor, some officers performed very accurately--though this was not related to
length of experience or training. We propose that improvements in security could
be made by emphasising personnel selection.
PMID- 25133683
TI - Lipid structure in triolein lipid droplets.
AB - Lipid droplets (LDs) are primary repositories of esterified fatty acids and
sterols in animal cells. These organelles originate on the lumenal or cytoplasmic
side of endoplasmic reticulum (ER) membrane and are released to the cytosol. In
contrast to other intracellular organelles, LDs are composed of a mass of
hydrophobic lipid esters coved by phospholipid monolayer. The small size and
unique architecture of LDs makes it complicated to study LD structure by modern
experimental methods. We discuss coarse-grained molecular dynamics (MD)
simulations of LD formation in systems containing 1-palmitoyl-2-oleoyl-sn-glycero
3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine
(POPE), triolein (TO), cholesterol (CHOL), and water. We find that (1) there is
more cholesterol in the LD core, than at the interface. (2) No crystallization
occurs inside the LD core. (3) According to coarse-grained simulations, the
presence of PE lipids at the interface has a little impact on distribution of
components and on the overall LD structure. (4) The thickness of the lipid
monolayer at the surface of the droplet is similar to the thickness of one
leaflet of a bilayer. Computer simulations are shown to be a mighty tool to
provide molecular-level insights, which are not available to the experimental
techniques.
PMID- 25133679
TI - Activated CD8+ T lymphocytes inhibit neural stem/progenitor cell proliferation:
role of interferon-gamma.
AB - The ability of neural stem/progenitor cells (NSCs) to self-renew, migrate to
damaged sites, and differentiate into neurons has renewed interest in using them
in therapies for neurodegenerative disorders. Neurological diseases, including
viral infections of the brain, are often accompanied by chronic inflammation,
whose impact on NSC function remains unexplored. We have previously shown that
chronic neuroinflammation, a hallmark of experimental herpes simplex encephalitis
(HSE) in mice, is dominated by brain-infiltrating activated CD8 T-cells. In the
present study, activated CD8 lymphocytes were found to suppress NSC proliferation
profoundly. Luciferase positive (luc+) NSCs co-cultured with activated, MHC
matched, CD8+ lymphocytes (luc-) showed two- to five-fold lower luminescence than
co-cultures with un-stimulated lymphocytes. On the other hand, similarly
activated CD4+ lymphocytes did not suppress NSC growth. This differential
lymphocyte effect on proliferation was confirmed by decreased BrdU uptake by NSC
cultured with activated CD8 T-cells. Interestingly, neutralizing antibodies to
interferon-gamma (IFN-gamma) reversed the impact of CD8 lymphocytes on NSCs.
Antibodies specific to the IFN-gamma receptor-1 subunit complex abrogated the
inhibitory effects of both CD8 lymphocytes and IFN-gamma, indicating that the
inhibitory effect of these cells was mediated by IFN-gamma in a receptor-specific
manner. In addition, activated CD8 lymphocytes decreased levels of nestin and
Sox2 expression in NSCs while increasing GFAP expression, suggesting possible
induction of an altered differentiation state. Furthermore, NSCs obtained from
IFN-gamma receptor-1 knock-out embryos were refractory to the inhibitory effects
of activated CD8+ T lymphocytes on cell proliferation and Sox2 expression. Taken
together, the studies presented here demonstrate a role for activated CD8 T-cells
in regulating NSC function mediated through the production of IFN-gamma. This
cytokine may influence neuro-restorative processes and ultimately contribute to
the long-term sequelae commonly seen following herpes encephalitis.
PMID- 25133684
TI - Three-dimensional flash flow microreactor for scale-up production of monodisperse
PEG-PLGA nanoparticles.
AB - We present a pressure-tolerant 3D parallel polyimide (PI) film microreactor
operating at up to ~160 bars with direct 3D flow focusing geometry for mass
production of PEG-PLGA nanoparticles in a ~10(1) gram-scale (g h(-1)).
PMID- 25133685
TI - Relationship between phylogeny and immunity suggests older Caribbean coral
lineages are more resistant to disease.
AB - Diseases affect coral species fitness and contribute significantly to the
deterioration of coral reefs. The increase in frequency and severity of disease
outbreaks has made evaluating and determining coral resistance a priority.
Phylogenetic patterns in immunity and disease can provide important insight to
how corals may respond to current and future environmental and/or biologically
induced diseases. The purpose of this study was to determine if immunity, number
of diseases and disease prevalence show a phylogenetic signal among Caribbean
corals. We characterized the constitutive levels of six distinct innate immune
traits in 14 Caribbean coral species and tested for the presence of a
phylogenetic signal on each trait. Results indicate that constitutive levels of
some individual immune related processes (i.e. melanin concentration, peroxidase
and inhibition of bacterial growth), as well as their combination show a
phylogenetic signal. Additionally, both the number of diseases affecting each
species and disease prevalence (as measures of disease burden) show a significant
phylogenetic signal. The phylogenetic signal of immune related processes,
combined with estimates of species divergence times, indicates that among the
studied species, those belonging to older lineages tend to resist/fight
infections better than more recently diverged coral lineages. This result,
combined with the increasing stressful conditions on corals in the Caribbean,
suggest that future reefs in the region will likely be dominated by older
lineages while modern species may face local population declines and/or
geographic extinction.
PMID- 25133686
TI - Transferred BCR/ABL DNA from K562 extracellular vesicles causes chronic myeloid
leukemia in immunodeficient mice.
AB - Our previous study showed that besides mRNAs and microRNAs, there are DNA
fragments within extracellular vesicles (EVs). The BCR/ABL hybrid gene, involved
in the pathogenesis of chronic myeloid leukemia (CML), could be transferred from
K562 EVs to neutrophils and decrease their phagocytic activity in vitro. Our
present study provides evidence that BCR/ABL DNAs transferred from EVs have
pathophysiological significance in vivo. Two months after injection of K562 EVs
into the tail vein of Sprague-Dawley (SD) rats, they showed some characteristics
of CML, e.g., feeble, febrile, and thin, with splenomegaly and neutrophilia but
with reduced neutrophil phagocytic activity. These findings were also observed in
immunodeficient NOD/SCID mice treated with K562 EVs; BCR/ABL mRNA and protein
were found in their neutrophils. The administration of actinomycin D, an
inhibitor of de novo mRNA synthesis, prevented the abnormalities caused by K562
EVs in NOD/SCID mice related to CML, including neutrophilia and bone marrow
hyperplasia. As a specific inhibitor of tyrosine kinases, imatinib blocked the
activity of tyrosine kinases and the expression of phospho-Crkl, induced by the
de novo BCR/ABL protein caused by K562 EVs bearing BCR/ABL DNA. Our current study
shows the pathophysiological significance of transferred tumor gene from EVs in
vivo, which may represent an important mechanism for tumorigenesis, tumor
progression, and metastasis.
PMID- 25133687
TI - Galleria mellonella model identifies highly virulent strains among all major
molecular types of Cryptococcus gattii.
AB - Cryptococcosis is mainly caused by Cryptococcus neoformans. However, the number
of cases due to C. gattii is increasing, affecting mainly immunocompetent hosts.
C. gattii is divided into four major molecular types, VGI to VGIV, which differ
in their host range, epidemiology, antifungal susceptibility and geographic
distribution. Besides studies on the Vancouver Island outbreak strains, which
showed that the subtype VGIIa is highly virulent compared to the subtype VGIIb,
little is known about the virulence of the other major molecular types. To
elucidate the virulence potential of the major molecular types of C. gattii,
Galleria mellonella larvae were inoculated with ten globally selected strains per
molecular type. Survival rates were recorded and known virulence factors were
studied. One VGII, one VGIII and one VGIV strain were more virulent (p <0.05)
than the highly virulent Vancouver Island outbreak strain VGIIa (CDCR265), 11
(four VGI, two VGII, four VGIII and one VGIV) had similar virulence (p >0.05), 21
(five VGI, five VGII, four VGIII and seven VGIV) were less virulent (p <0.05)
while one strain of each molecular type were avirulent. Cell and capsule size of
all strains increased markedly during larvae infection (p <0.001). No differences
in growth rate at 37 degrees C were observed. Melanin synthesis was directly
related with the level of virulence: more virulent strains produced more melanin
than less virulent strains (p <0.05). The results indicate that all C. gattii
major molecular types exhibit a range of virulence, with some strains having the
potential to be more virulent. The study highlights the necessity to further
investigate the genetic background of more and less virulent strains in order to
recognize critical features, other than the known virulence factors (capsule,
melanin and growth at mammalian body temperature), that maybe crucial for the
development and progression of cryptococcosis.
PMID- 25133689
TI - Lack of evidence for lower mercury biomagnification by biomass dilution in more
productive lakes: comment on "Mercury biomagnification through food webs is
affected by physical and chemical characteristics of lakes".
PMID- 25133691
TI - Two-dimensional TaSe2 metallic crystals: spin-orbit scattering length and
breakdown current density.
AB - We have determined the spin-orbit scattering length of two-dimensional layered 2H
TaSe2 metallic crystals by detailed characterization of the weak antilocalization
phenomena in this strong spin-orbit interaction material. By fitting the observed
magneto-conductivity, the spin-orbit scattering length for 2H-TaSe2 is determined
to be 17 nm in the few-layer films. This small spin-orbit scattering length is
comparable to that of Pt, which is widely used to study the spin Hall effect, and
indicates the potential of TaSe2 for use in spin Hall effect devices. A material
must also support large charge currents in addition to strong spin-orbit coupling
to achieve spin-transfer-torque via the spin Hall effect. Therefore, we have
characterized the room temperature breakdown current density of TaSe2 in air,
where the best breakdown current density reaches 3.7 * 10(7) A/cm(2). This large
breakdown current further indicates the potential of TaSe2 for use in spin-torque
devices and two-dimensional device interconnect applications.
PMID- 25133690
TI - Episodic bradycardia as neurocardiac prodrome to voltage-gated potassium channel
complex/leucine-rich, glioma inactivated 1 antibody encephalitis.
AB - IMPORTANCE: Voltage-gated potassium channel complex antibody (VGKCc-Ab)
encephalitis is an immunotherapy-responsive syndrome usually associated with
causative antibodies that target the leucine-rich, glioma inactivated 1 (LGI1)
protein. Although it is expressed throughout the brain, LGI1 is not known to be
expressed in cardiac tissue. We describe a novel neurocardiac prodrome of VGKCc
Ab/LGI1-encephalitis. OBSERVATIONS: Among 14 patients with VGKCc/LGI1-Ab
encephalitis evaluated in the University of California, San Francisco Autoimmune
Encephalitis Clinic and Rapid Dementia Research Program, 3 patients (2 men and 1
woman; aged 53, 55, and 64 years) exhibited episodic bradycardia that preceded
the onset of encephalopathy by approximately 2 months and was severe enough to
lead to pacemaker implantation. Serum LGI1-Ab results were positive when tested
at the time of the subsequent encephalopathy. All 3 patients developed
hyponatremia; none had faciobrachial dystonic seizures or malignancy. Brain
magnetic resonance imaging was abnormal in 2 cases. None of the patients
experienced further symptomatic bradyarrythmias after 1.7 to 7 years of follow
up. CONCLUSIONS AND RELEVANCE: Episodic bradycardia is a distinctive neurocardiac
prodrome of VGKCc/LGI1-Ab encephalitis. The neuroanatomical localization most
likely relates to insular and temporal lobe involvement, cortical regions that
modulate cardiac autonomic function. Further study is needed to determine if
recognition of this neurocardiac prodrome and earlier institution of
immunosuppression can prevent the development of encephalopathy.
PMID- 25133692
TI - Diabetes mellitus aggravates hemorrhagic transformation after ischemic stroke via
mitochondrial defects leading to endothelial apoptosis.
AB - Diabetes is a crucial risk factor for stroke and is associated with increased
frequency and poor prognosis. Although endothelial dysfunction is a known
contributor of stroke, the underlying mechanisms have not been elucidated. The
aim of this study was to elucidate the mechanism by which chronic hyperglycemia
may contribute to the worsened prognosis following stroke, especially focusing on
mitochondrial alterations. We examined the effect of hyperglycemia on hemorrhagic
transformation at 24 hours after middle cerebral artery occlusion (MCAO) in
streptozotocin (STZ) -induced diabetic mice. We also examined the effects of high
glucose exposure for 6 days on cell death, mitochondrial functions and morphology
in human brain microvascular endothelial cells (HBMVECs) or human endothelial
cells derived from induced pluripotent stem cells (iCell endothelial cells).
Hyperglycemia aggravated hemorrhagic transformation, but not infarction following
stroke. High-glucose exposure increased apoptosis, capase-3 activity, and release
of apoptosis inducing factor (AIF) and cytochrome c in HBMVECs as well as
affected mitochondrial functions (decreased cell proliferation, ATP contents,
mitochondrial membrane potential, and increased matrix metalloproteinase (MMP)-9
activity, but not reactive oxygen species production). Furthermore, morphological
aberration of mitochondria was observed in diabetic cells (a great deal of
fragmentation, vacuolation, and cristae disruption). A similar phenomena were
seen also in iCell endothelial cells. In conclusion, chronic hyperglycemia
aggravated hemorrhagic transformation after stroke through mitochondrial
dysfunction and morphological alteration, partially via MMP-9 activation, leading
to caspase-dependent apoptosis of endothelial cells of diabetic mice.
Mitochondria-targeting therapy may be a clinically innovative therapeutic
strategy for diabetic complications in the future.
PMID- 25133688
TI - Targeting the ubiquitin-proteasome system in heart disease: the basis for new
therapeutic strategies.
AB - SIGNIFICANCE: Novel therapeutic strategies to treat heart failure are greatly
needed. The ubiquitin-proteasome system (UPS) affects the structure and function
of cardiac cells through targeted degradation of signaling and structural
proteins. This review discusses both beneficial and detrimental consequences of
modulating the UPS in the heart. RECENT ADVANCES: Proteasome inhibitors were
first used to test the role of the UPS in cardiac disease phenotypes, indicating
therapeutic potential. In early cardiac remodeling and pathological hypertrophy
with increased proteasome activities, proteasome inhibition prevented or
restricted disease progression and contractile dysfunction. Conversely, enhancing
proteasome activities by genetic manipulation, pharmacological intervention, or
ischemic preconditioning also improved the outcome of cardiomyopathies and
infarcted hearts with impaired cardiac and UPS function, which is, at least in
part, caused by oxidative damage. CRITICAL ISSUES: An understanding of the UPS
status and the underlying mechanisms for its potential deregulation in cardiac
disease is critical for targeted interventions. Several studies indicate that
type and stage of cardiac disease influence the dynamics of UPS regulation in a
nonlinear and multifactorial manner. Proteasome inhibitors targeting all
proteasome complexes are associated with cardiotoxicity in humans. Furthermore,
the type and dosage of proteasome inhibitor impact the pathogenesis in nonuniform
ways. FUTURE DIRECTIONS: Systematic analysis and targeting of individual UPS
components with established and innovative tools will unravel and discriminate
regulatory mechanisms that contribute to and protect against the progression of
cardiac disease. Integrating this knowledge in drug design may reduce adverse
effects on the heart as observed in patients treated with proteasome inhibitors
against noncardiac diseases, especially cancer.
PMID- 25133695
TI - Complete mitochondrial genome sequence of the longsnout seahorse Hippocampus
reidi (Ginsburg, 1933; Gasterosteiformes: Syngnathidae).
AB - The complete mitochondrial genome sequence of the longsnout seahorse Hippocampus
reidi was fisrt determined in this article. The total length of H. reidi
mitogenome is 16,529 bp and consists of 13 protein-coding genes, 2 rRNA genes, 22
tRNA genes and 1 control region. The gene order and composition of H. reidi were
similar to those of most other vertebrates. The overall base composition of H.
reidi is 32.47% A, 29.41% T, 14.75% G and 23.37% C, with a slight A + T rich
feature (61.88%).
PMID- 25133694
TI - The minor wall-networks between monolignols and interlinked-phenolics
predominantly affect biomass enzymatic digestibility in Miscanthus.
AB - Plant lignin is one of the major wall components that greatly contribute to
biomass recalcitrance for biofuel production. In this study, total 79
representative Miscanthus germplasms were determined with wide biomass
digestibility and diverse monolignol composition. Integrative analyses indicated
that three major monolignols (S, G, H) and S/G ratio could account for lignin
negative influence on biomass digestibility upon NaOH and H2SO4 pretreatments.
Notably, the biomass enzymatic digestions were predominately affected by the non
KOH-extractable lignin and interlinked-phenolics, other than the KOH-extractable
ones that cover 80% of total lignin. Furthermore, a positive correlation was
found between the monolignols and phenolics at p<0.05 level in the non-KOH
extractable only, suggesting their tight association to form the minor wall
networks against cellulases accessibility. The results indicated that the non-KOH
extractable lignin-complex should be the target either for cost-effective biomass
pretreatments or for relatively simply genetic modification of plant cell walls
in Miscanthus.
PMID- 25133693
TI - Dopamine D2-like receptors modulate unconditioned fear: role of the inferior
colliculus.
AB - BACKGROUND: A reduction of dopamine release or D2 receptor blockade in the
terminal fields of the mesolimbic system clearly reduces conditioned fear.
Injections of haloperidol, a preferential D2 receptor antagonist, into the
inferior colliculus (IC) enhance the processing of unconditioned aversive
information. However, a clear characterization of the interplay of D2 receptors
in the mediation of unconditioned and conditioned fear is still lacking. METHODS:
The present study investigated the effects of intra-IC injections of the D2
receptor-selective antagonist sulpiride on behavior in the elevated plus maze
(EPM), auditory-evoked potentials (AEPs) to loud sounds recorded from the IC,
fear-potentiated startle (FPS), and conditioned freezing. RESULTS: Intra-IC
injections of sulpiride caused clear proaversive effects in the EPM and enhanced
AEPs induced by loud auditory stimuli. Intra-IC sulpiride administration did not
affect FPS or conditioned freezing. CONCLUSIONS: Dopamine D2-like receptors of
the inferior colliculus play a role in the modulation of unconditioned aversive
information but not in the fear-potentiated startle response.
PMID- 25133696
TI - The complete mitogenome of Xenophysogobio boulengeri (Cypriniformes; Cyprinidae).
AB - Xenophysogobio boulengeri is an endemic fish to mainstream and most tributaries
of the upper Yangtze River. The complete mitochondrial genome sequence of X.
boulengeri has been amplified and sequenced. The mitochondrial genome sequence
was 16,611 bp, and the gene order and contents were identical with that of other
previously reported fish with 2 rRNA genes, 13 protein-coding genes, 22 tRNA
genes, and a non-coding control region. Most of genes were encoded by Heavy
Strand (H-strand), except 8 tRNA and ND6 genes, which were encoded by Light
Strand (L-strand). Base composition of the genome was A (30.8%), T (27.0%), C
(25.8%) and G (16.4%) with an A+T rich feature as that of other vertebrate
mitochondrial genomes.
PMID- 25133697
TI - The complete mitochondrial genome of the hybrid of Siniperca chuatsi (?) *
Siniperca kneri (?).
AB - In this study, we reported the complete mitochondrial DNA sequence of the hybrid
of Siniperca chuatsi (?)*Siniperca kneri (?). The total length of the
mitochondrial genome is 16,493 bp, with the base composition of 28.61% A, 29.21%
C, 16.21% G, and 25.97% T. It contains 2 rRNA genes, 13 protein-coding genes, 22
tRNA genes, and a major non-coding control region (D-loop region). The
composition and order of these genes are identical to most of other vertebrates.
All the protein initiation codons are ATG, except for COX1 that begins with GTG.
The complete mitogenome of the hybrid of Siniperca chuatsi (?) * Siniperca kneri
(?) provides an important data set for the study in genetic mechanism.
PMID- 25133698
TI - The complete mitogenome of Gnathopogon polytaenia (Cypriniformes; Cyprinidae).
AB - The complete mitochondrial genome was sequenced from one of the endemic
freshewater gudgeons (Gnathopogon polytaenia) in China. The mitochondrial genome
sequence was 16,594 bp in size, and the gene order and contents were identical
with the congeneric species G. strigatus and G. elongatus. Six genes (COII, ATP6,
COIII, ND3, ND4, Cytb) had an incomplete stop codon. Base composition of the
genome is A (29.1%), T (26.9%), C (25.9%) and G (18.1%) with an A + T rich
feature (56%) as that of other vertebrate mitochondrial genomes.
PMID- 25133700
TI - Ultrasound-assisted sequential multicomponent strategy for the combinatorial
synthesis of novel coumarin hybrids.
AB - The present investigation reports an easy access to a library of novel spiro
oxindole-pyrrolizine or pyrrolo[1,2-c]thiazole fused coumarin hybrid heterocycles
through a one-pot sequential four-component reactions of 2,2-dimethyl-1,3-dioxane
4,6-dione, salicylaldehydes, isatins, and cyclic alpha-amino acids under
ultrasound irradiation.
PMID- 25133699
TI - A novel glycated hemoglobin A1c-lowering traditional Chinese medicinal formula,
identified by translational medicine study.
AB - Diabetes is a chronic metabolic disorder that has a significant impact on the
health care system. The reduction of glycated hemoglobin A1c is highly associated
with the improvements of glycemic control and diabetic complications. In this
study, we identified a traditional Chinese medicinal formula with a HbA1c
lowering potential from clinical evidences. By surveying 9,973 diabetic patients
enrolled in Taiwan Diabetic Care Management Program, we found that Chu-Yeh-Shih
Kao-Tang (CYSKT) significantly reduced HbA1c values in diabetic patients. CYSKT
reduced the levels of HbA1c and fasting blood glucose, and stimulated the blood
glucose clearance in type 2 diabetic mice. CYSKT affected the expressions of
genes associated with insulin signaling pathway, increased the amount of
phosphorylated insulin receptor in cells and tissues, and stimulated the
translocation of glucose transporter 4. Moreover, CYSKT affected the expressions
of genes related to diabetic complications, improved the levels of renal function
indexes, and increased the survival rate of diabetic mice. In conclusion, this
was a translational medicine study that applied a "bedside-to-bench" approach to
identify a novel HbA1c-lowering formula. Our findings suggested that oral
administration of CYSKT affected insulin signaling pathway, decreased HbA1c and
blood glucose levels, and consequently reduced mortality rate in type 2 diabetic
mice.
PMID- 25133701
TI - Zonisamide: pharmacokinetics, efficacy, and adverse events in children with
epilepsy.
AB - BACKGROUND: Zonisamide is a new generation antiepileptic drug (AED) widely used
in children with refractory epilepsy, although until recently, it was used to a
large extent as off-label or unlicensed medication due to the lack of evidence
based studies. Children have a different pharmacokinetic profile than adults and
an adult dose regimen cannot be directly translated into pediatric use. Patients
and METHODS: In this retrospective noninterventional study of the medical records
of 75 children with pharmacoresistant epilepsy, the pharmacokinetics, efficacy
and safety of zonisamide were examined. The dose-to-concentration ratio, the
daily weight-normalized dose of zonisamide divided by its plasma concentration,
was used as a measure of clearance. In addition, data on the efficacy of
zonisamide to reduce seizures and reported adverse events were extracted from the
medical records and analyzed. RESULTS: Young children (range, 0-4 years) had a
significantly increased zonisamide clearance compared with older ones (range, 5
17 years) and those with enzyme-inducing comedication (carbamazepine,
phenobarbital, or phenytoin) had increased clearance compared with those on
nonenzyme inducers; the increases were 1.7-fold and 1.8-fold, respectively. No
significant difference in clearance was found between female and male subjects.
The clearances of concomitant AEDs were not affected by zonisamide
administration. The overall efficacy of zonisamide for reducing seizure frequency
>= 50% was 35% and the most frequent adverse event was fatigue, reported in 23%
of the patients. CONCLUSION: Patients with enzyme-inducing comedication or of
young age (range, 0-4 years) might need higher weight-normalized doses to achieve
the same plasma levels as in patients with no enzyme-inducing comedication or
patients of older age. Zonisamide was not found to influence the pharmacokinetics
of concomitant AEDs. The shortage of pharmacokinetic studies of zonisamide in
children highlights the need for research of this kind.
PMID- 25133702
TI - Surprising quenching of the spin-orbit interaction significantly diminishes
H2O...X [X = F, Cl, Br, I] dissociation energies.
AB - The H2O...X complexes, with X = F, Cl, Br, and I, show considerable viability
with nonspin-orbit De(D0) dissociation energy values of 3.73(2.42), 3.60(2.68),
3.54(2.72), and 3.36(2.77) kcal mol(-1) for X = F, Cl, Br, and I, respectively,
obtained at the CCSD(T)-F12b/aug-cc-pVTZ(-PP) level of theory using relativistic
pseudopotentials (PPs) for Br and I. Spin-orbit (SO) corrections, computed with
the Breit-Pauli operator in the interacting states approach at the all-electron
MRCI+Q/aug-cc-pwCVTZ(-PP) level, are found to depend sensitively and
unpredictably on the O...X separations. 96% (F), 87% (Cl), 54% (Br), and 30% (I)
quenching of the SO corrections significantly reduces the dissociation energies
of the H2O...X complexes, resulting in De(D0) values of 3.38(2.06), 2.86(1.94),
1.64(0.83), and 1.23(0.64) kcal mol(-1) for X = F, Cl, Br, and I, respectively.
PMID- 25133703
TI - Nanoparticle surface characterization and clustering through concentration
dependent surface adsorption modeling.
AB - Quantitative characterization of nanoparticle interactions with their surrounding
environment is vital for safe nanotechnological development and standardization.
A recent quantitative measure, the biological surface adsorption index (BSAI),
has demonstrated promising applications in nanomaterial surface characterization
and biological/environmental prediction. This paper further advances the approach
beyond the application of five descriptors in the original BSAI to address the
concentration dependence of the descriptors, enabling better prediction of the
adsorption profile and more accurate categorization of nanomaterials based on
their surface properties. Statistical analysis on the obtained adsorption data
was performed based on three different models: the original BSAI, a concentration
dependent polynomial model, and an infinite dilution model. These advancements in
BSAI modeling showed a promising development in the application of quantitative
predictive modeling in biological applications, nanomedicine, and environmental
safety assessment of nanomaterials.
PMID- 25133705
TI - Detection and molecular characterization of infectious bronchitis-like viruses in
wild bird populations.
AB - We examined 884 wild birds mainly from the Anseriformes, Charadriiformes and
Galliformes orders for infectious bronchitis (IBV)-like coronavirus in Poland
between 2008 and 2011. Coronavirus was detected in 31 (3.5%) of the tested birds,
with detection rates of 3.5% in Anseriformes and 2.3% in Charadriiformes and as
high as 17.6% in Galliformes. From the 31 positive samples, only 10 gave positive
results in molecular tests aimed at various IBV genome fragments: five samples
were positive for the RdRp gene, four for gene 3, eight for gene N and eight for
the 3'-untranslated region fragment. All analysed genome fragments of the
coronavirus strains shared different evolutionary branches, resulting in a
different phylogenetic tree topology. Most detected fragment genes seem to be IBV
like genes of the most frequently detected lineages of IBV in this geographical
region (i.e. Massachusetts, 793B and QX). Two waves of coronavirus infections
were identified: one in spring (April and May) and another in late autumn
(October to December). To our knowledge this is the first report of the detection
of different fragment IBV-like genes in wild bird populations.
PMID- 25133704
TI - Molecular dynamics study of binding of u-conotoxin GIIIA to the voltage-gated
sodium channel Na(v)1.4.
AB - Homology models of mammalian voltage-gated sodium (NaV) channels based on the
crystal structures of the bacterial counterparts are needed to interpret the
functional data on sodium channels and understand how they operate. Such models
would also be invaluable in structure-based design of therapeutics for diseases
involving sodium channels such as chronic pain and heart diseases. Here we
construct a homology model for the pore domain of the NaV1.4 channel and use the
functional data for the binding of u-conotoxin GIIIA to NaV1.4 to validate the
model. The initial poses for the NaV1.4-GIIIA complex are obtained using the
HADDOCK protein docking program, which are then refined in molecular dynamics
simulations. The binding mode for the final complex is shown to be in broad
agreement with the available mutagenesis data. The standard binding free energy,
determined from the potential of mean force calculations, is also in good
agreement with the experimental value. Because the pore domains of NaV1 channels
are highly homologous, the model constructed for NaV1.4 will provide an excellent
template for other NaV1 channels.
PMID- 25133706
TI - High-grade endometrial stromal sarcomas: a clinicopathologic study of a group of
tumors with heterogenous morphologic and genetic features.
AB - The existence of a "high-grade endometrial stromal sarcoma" category of tumors
has been a controversial subject owing to, among other things, the difficulty in
establishing consistent diagnostic criteria. Currently, the recommended
classification for such tumors is undifferentiated uterine/endometrial sarcoma.
Interest in this subject has recently increased markedly with the identification
of recurrent molecular genetic abnormalities. At Mayo Clinic, a group of
neoplasms has been observed that morphologically resemble, either cytologically
or architecturally, classic "low-grade" endometrial stromal sarcoma but feature
obvious deviations, specifically, 17 tumors with unequivocally high-grade
morphology. These high-grade tumors displayed 3 morphologic themes: (1) tumors
with a component that is identical to low-grade ESS that transitions abruptly
into an obviously higher-grade component; (2) tumors composed exclusively of high
grade cells with uniform nuclear features but with a permeative pattern of
infiltration; (3) tumors similar to the second group but with a different, yet
characteristic, cytomorphology featuring enlarged round to ovoid cells (larger
than those found in low-grade ESS) with smooth nuclear membranes and distinct
chromatin clearing but lacking prominent nucleoli. We collected clinicopathologic
data, applied immunohistochemical studies, and also tested tumors by fluorescence
in situ hybridization for abnormalities in JAZF1, PHF1, YWHAE, and CCND1. Tumors
from these 3 groups were found to be immunohistochemically and genetically
distinct from one another. Most notable was the fact that category 3 contained
all the cases that tested positive for YWHAE rearrangement, did not show any
classic translocations for JAZF1, PHF1, or CCND1, often presented at a high
stage, and behaved aggressively. This study demonstrates the morphologic,
immunophenotypic, and molecular genetic heterogeneity that exists within
"undifferentiated endometrial sarcomas" as currently defined and lends credence
to the effort of subclassifying some tumors as truly "high-grade endometrial
stromal sarcomas." Our study also shows that, in the context of undifferentiated
endometrial sarcomas, recognition of cytomorphologic features on routine
hematoxylin and eosin-stained sections may be used to select tumors with specific
molecular genetic changes-that is, translocations involving YWHAE. Our
conclusions will help further efforts towards proper sub-classification of these
tumors which will aid in diagnosis and potentially affect clinical management.
PMID- 25133707
TI - Assessing the HER2 status in mucinous epithelial ovarian cancer on the basis of
the 2013 ASCO/CAP guideline update.
AB - Her2 gene amplification and protein overexpression are important factors in
predicting clinical sensitivity to anti-HER2 monoclonal antibody therapy in
breast, gastric, or gastro-esophageal junction cancer patients. The purpose of
this study was to evaluate the HER2 status in the mucinous epithelial ovarian
cancer (EOC). Adopting the 2013 American Society for Clinical Oncology and the
College of American Pathologists guideline update for HER2 testing, 49 tissue
microarray samples of mucinous EOC were analyzed by immunohistochemistry (IHC)
and fluorescence in situ hybridization (FISH) tests. The prevalence of HER2
positivity in Asian mucinous EOC was 9 of 49 Asian women (18.37%). The overall
concordance was 100% between IHC and FISH results. Her2 gene copies before
chromosome-17 correction increased significantly in a stepwise order through the
negative, equivocal, and positive IHC result categories (P<0.001), as did the
Her2 gene copies after chromosome-17 correction (P<0.001). Of the Taiwanese
cohort (n=21), HER2 heterogeneity was 4.76% (1/21) in all but 14.26% (1/7) in
HER2-positive cancer. In conclusion, we demonstrated that the prevalence of HER2
positivity in both Asian and white women was comparable; complete HER2
concordance existed between IHC and FISH tests for the Her2 gene copies per tumor
cell either before or after correction of chromosome-17, and this can be applied
as a potentially valuable tool to analyze the HER2 status. Polysomy-17 was absent
under the CEP17 cutoff >=3. The existence of HER2 heterogeneity can be discerned
in certain HER2-expressed primary mucinous EOC in Taiwanese women.
PMID- 25133708
TI - Pseudoangiosarcomatous urothelial carcinoma of the urinary bladder.
AB - The pseudoangiosarcomatous pattern has been described mostly in cutaneous and
some visceral squamous cell carcinomas and is unique for its striking morphologic
resemblance to angiosarcoma. Herein, we describe the clinicopathologic features
of 7 pseudoangiosarcomatous urothelial carcinomas that occurred in the urinary
bladder. The patients included 6 men and 1 woman ranging in age from 47 to 87
years (median 70 y). The pseudoangiosarcomatous morphology was observed in 7
urothelial carcinomas including 3 with squamous differentiation and comprised 35%
to 85% of the invasive tumor. Histologically, the pseudoangiosarcomatous
carcinomas were characterized by tumor cell discohesion and lysis that created
pseudolumina formations surrounded by attached residual tumor cells. Detached
degenerating tumor cells variably admixed with inflammatory cells were common in
the false lumina. Partly intact urothelial carcinoma nests contained irregular or
cleft-like spaces and disintegrating tumor cells with stretched intercellular
bridges. The tumor was commonly associated with a dense collagenous matrix, often
surrounding the lytic nests. Similar tumor cell discohesion and breakdown were
observed in 3 tumors with foci of squamous cell differentiation, distinguished by
the presence of dyskeratosis and keratin formation. All 7 tumors contained other
nonpseudoangiosarcomatous carcinoma components such as conventional urothelial
carcinoma (5), squamous differentiation (4), sarcomatoid spindle cell carcinoma
(2), small cell carcinoma (1), micropapillary carcinoma (1), and glandular
differentiation (1). The pseudoangiosarcomatous urothelial carcinomas were all
(7/7) diffusely CK7 positive, most (6/7) were GATA3 positive, and none (0/7)
expressed vascular-associated markers. There was no evidence to suggest that
apoptosis (by TUNEL assay and cleaved caspase-3 immunostaining) or loss of the
adhesion molecules CD138 and e-cadherin were possible causes for the tumor cell
discohesion and breakdown. All 7 tumors were high stage at cystectomy and
included 1 pT3a, 2 pT3b, and 4 pT4a tumors, and 3 had pelvic lymph node
involvement. Follow-up data available in 6 cases revealed a poor outcome with an
overall median survival of 8.5 months. In conclusion, we present an unusual
morphology of bladder carcinoma that has a striking resemblance to a malignant
vasoformative tumor. Our series showed that bladder pseudoangiosarcomatous
carcinoma morphology is associated with a higher tumor stage at cystectomy,
commonly admixed with other aggressive carcinoma variant morphologies, and
portend a poorer outcome. Knowledge of this pattern is also important to avoid
misdiagnosis, particularly in limited tissue samples.
PMID- 25133709
TI - Health-related quality of life measurement in siblings of children with physical
chronic illness: a systematic review.
AB - The diagnosis of a physical chronic illness during childhood can cause stressors
and changes within the family system that place family members at-risk for
impaired functioning. The objective of the present study was to perform a
systematic review on the health-related quality of life (HRQOL) of siblings of
children with physical chronic health conditions. Three independent reviewers
performed the search in the databases PsycINFO and PubMed, which resulted in 9
studies meeting full inclusion criteria. Overall, sibling HRQOL was better than
children with a physical chronic illness. Parents of siblings of children with
physical chronic illness tended to rate sibling HRQOL better than siblings self
reports. Greater disease severity emerged as a potential risk factor for impaired
sibling HRQOL. These data underscore the importance of assessing sibling HRQOL in
families with a child who has been diagnosed with a physical chronic illness.
Future research is needed in this area with larger sibling samples and across a
greater variety of childhood chronic illnesses.
PMID- 25133710
TI - Protein supplementation increases postexercise plasma myostatin concentration
after 8 weeks of resistance training in young physically active subjects.
AB - Myostatin (MSTN) is a negative regulator of muscle growth even if some studies
have shown a counterintuitive positive correlation between MSTN and muscle mass
(MM). Our aim was to investigate the influence of 2 months of resistance training
(RT) and diets with different protein contents on plasma MSTN, interleukin 1 beta
(IL-1beta), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and
insulin-like growth factor 1 (IGF-1). Eighteen healthy volunteers were randomly
divided in two groups: high protein (HP) and normal protein (NP) groups.
Different protein diet contents were 1.8 and 0.85 g of protein.kg bw(-1).day(-1)
for HP and NP, respectively. Subjects underwent 8 weeks of standardized
progressive RT. MSTN, IGF-1, IL-1beta, IL-6, and TNF-alpha were analyzed before
and after the first and the last training sessions. Lean body mass, MM, upper
limb muscle area, and strength were measured. Plasma MSTN showed a significant
increase (P<.001) after the last training in the HP group compared with NP group
and with starting value. IGF-1 plasma concentration showed a positive correlation
with MSTN in HP after the last training (r(2)=0.6456; P=.0295). No significant
differences were found between NP and HP for IL-1beta, IL-6, TNF-alpha, and
strength and MM or area. These findings suggest a "paradoxical" postexercise
increase of plasma MSTN after 8 weeks of RT and HP diets. This MSTN elevation
correlates positively with IGF-1 plasma level. This double increase of opposite
(catabolic/anabolic) mediators could explain the substantial overlapping of MM
increases in the two groups.
PMID- 25133712
TI - Phylogenetic analyses and characterization of RNase X25 from Drosophila
melanogaster suggest a conserved housekeeping role and additional functions for
RNase T2 enzymes in protostomes.
AB - Ribonucleases belonging to the RNase T2 family are enzymes associated with the
secretory pathway that are almost absolutely conserved in all eukaryotes. Studies
in plants and vertebrates suggest they have an important housekeeping function in
rRNA recycling. However, little is known about this family of enzymes in
protostomes. We characterized RNase X25, the only RNase T2 enzyme in Drosophila
melanogaster. We found that RNase X25 is the major contributor of ribonuclease
activity in flies as detected by in gel assays, and has an acidic pH preference.
Gene expression analyses showed that the RNase X25 transcript is present in all
adult tissues and developmental stages. RNase X25 expression is elevated in
response to nutritional stresses; consistent with the hypothesis that this enzyme
has a housekeeping role in recycling RNA. A correlation between induction of
RNase X25 expression and autophagy was observed. Moreover, induction of gene
expression was triggered by oxidative stress suggesting that RNase X25 may have
additional roles in stress responses. Phylogenetic analyses of this family in
protostomes showed that RNase T2 genes have undergone duplication events followed
by divergence in several phyla, including the loss of catalytic residues, and
suggest that RNase T2 proteins have acquired novel functions. Among those, it is
likely that a role in host immunosuppression evolved independently in several
groups, including parasitic Platyhelminthes and parasitoid wasps. The presence of
only one RNase T2 gene in the D. melanogaster genome, without any other evident
secretory RNase activity detected, makes this organism an ideal system to study
the cellular functions of RNase T2 proteins associated with RNA recycling and
maintenance of cellular homeostasis. On the other hand, the discovery of gene
duplications in several protostome genomes also presents interesting new avenues
to study additional biological functions of this ancient family of proteins.
PMID- 25133715
TI - The Situational Eight DIAMONDS: a taxonomy of major dimensions of situation
characteristics.
AB - Taxonomies of person characteristics are well developed, whereas taxonomies of
psychologically important situation characteristics are underdeveloped. A working
model of situation perception implies the existence of taxonomizable dimensions
of psychologically meaningful, important, and consequential situation
characteristics tied to situation cues, goal affordances, and behavior. Such
dimensions are developed and demonstrated in a multi-method set of 6 studies.
First, the "Situational Eight DIAMONDS" dimensions Duty, Intellect, Adversity,
Mating, pOsitivity, Negativity, Deception, and Sociality (Study 1) are
established from the Riverside Situational Q-Sort (Sherman, Nave, & Funder, 2010,
2012, 2013; Wagerman & Funder, 2009). Second, their rater agreement (Study 2) and
associations with situation cues and goal/trait affordances (Studies 3 and 4) are
examined. Finally, the usefulness of these dimensions is demonstrated by
examining their predictive power of behavior (Study 5), particularly vis-a-vis
measures of personality and situations (Study 6). Together, we provide extensive
and compelling evidence that the DIAMONDS taxonomy is useful for organizing major
dimensions of situation characteristics. We discuss the DIAMONDS taxonomy in the
context of previous taxonomic approaches and sketch future research directions.
PMID- 25133714
TI - Observing a movement correction during walking affects evoked responses but not
unperturbed walking.
AB - Seeing an action activates neurons in the premotor, motor, and somatosensory
cortex. Since a significant fraction of these pyramidal neurons project to the
spinal motor circuits, a central question is why we do not automatically perform
the actions that we see. Indeed, seeing an action increases both cortical and
spinal excitability of consistent motor patterns that correspond to the observed
ones. Thus, it is believed that such imitative motor patterns are either
suppressed or remain at a sub-threshold level. This would predict, however, that
seeing someone make a corrective movement while one is actively involved in the
same action should either suppress evoked responses or suppress or modulate the
action itself. Here we tested this prediction, and found that seeing someone
occasionally stepping over an obstacle while walking on a treadmill did not
affect the normal walking pattern at all. However, cutaneously evoked reflexes in
the anterior tibial and soleus muscles were modulated as if the subject was
stepping over an obstacle. This result thus indicates that spinal activation was
not suppressed and was neither at sub-threshold motor resonance. Rather, the
spinal modulation from observed stepping reflects an adaptive mechanism for
regulating predictive control mechanisms. We conclude that spinal excitability
during action observation is not an adverse side-effect of action understanding
but reflects adaptive and predictive motor control.
PMID- 25133716
TI - Moral character in the workplace.
AB - Using two 3-month diary studies and a large cross-sectional survey, we identified
distinguishing features of adults with low versus high levels of moral character.
Adults with high levels of moral character tend to: consider the needs and
interests of others and how their actions affect other people (e.g., they have
high levels of Honesty-Humility, empathic concern, guilt proneness); regulate
their behavior effectively, specifically with reference to behaviors that have
positive short-term consequences but negative long-term consequences (e.g., they
have high levels of Conscientiousness, self-control, consideration of future
consequences); and value being moral (e.g., they have high levels of moral
identity-internalization). Cognitive moral development, Emotionality, and social
value orientation were found to be relatively undiagnostic of moral character.
Studies 1 and 2 revealed that employees with low moral character committed
harmful work behaviors more frequently and helpful work behaviors less frequently
than did employees with high moral character, according to their own admissions
and coworkers' observations. Study 3 revealed that adults with low moral
character committed more delinquent behavior and had more lenient attitudes
toward unethical negotiation tactics than did adults with high moral character.
By showing that individual differences have consistent, meaningful effects on
employees' behaviors, after controlling for demographic variables (e.g., gender,
age, income) and basic attributes of the work setting (e.g., enforcement of an
ethics code), our results contest situationist perspectives that deemphasize the
importance of personality. Moral people can be identified by self-reports in
surveys, and these self-reports predict consequential behaviors months after the
initial assessment.
PMID- 25133713
TI - Subchronic treatment of donepezil rescues impaired social, hyperactive, and
stereotypic behavior in valproic acid-induced animal model of autism.
AB - Autism spectrum disorder (ASD) is a group of pervasive developmental disorders
with core symptoms such as sociability deficit, language impairment, and
repetitive/restricted behaviors. Although worldwide prevalence of ASD has been
increased continuously, therapeutic agents to ameliorate the core symptoms
especially social deficits, are very limited. In this study, we investigated
therapeutic potential of donepezil for ASD using valproic acid-induced autistic
animal model (VPA animal model). We found that prenatal exposure of valproic acid
(VPA) induced dysregulation of cholinergic neuronal development, most notably the
up-regulation of acetylcholinesterase (AChE) in the prefrontal cortex of affected
rat and mouse offspring. Similarly, differentiating cortical neural progenitor
cell in culture treated with VPA showed increased expression of AChE in vitro.
Chromatin precipitation experiments revealed that acetylation of histone H3 bound
to AChE promoter region was increased by VPA. In addition, other histone
deacetyalse inhibitors (HDACIs) such as trichostatin A and sodium butyrate also
increased the expression of AChE in differentiating neural progenitor cells
suggesting the essential role of HDACIs in the regulation of AChE expression. For
behavioral analysis, we injected PBS or donepezil (0.3 mg/kg) intraperitoneally
to control and VPA mice once daily from postnatal day 14 all throughout the
experiment. Subchronic treatment of donepezil improved sociability and prevented
repetitive behavior and hyperactivity of VPA-treated mice offspring. Taken
together, these results provide evidence that dysregulation of ACh system
represented by the up-regulation of AChE may serve as an effective
pharmacological therapeutic target against autistic behaviors in VPA animal model
of ASD, which should be subjected for further investigation to verify the
clinical relevance.
PMID- 25133718
TI - "I'd only let you down": Guilt proneness and the avoidance of harmful
interdependence.
AB - Five studies demonstrated that highly guilt-prone people may avoid forming
interdependent partnerships with others whom they perceive to be more competent
than themselves, as benefitting a partner less than the partner benefits one's
self could trigger feelings of guilt. Highly guilt-prone people who lacked
expertise in a domain were less willing than were those low in guilt proneness
who lacked expertise in that domain to create outcome-interdependent
relationships with people who possessed domain-specific expertise. These highly
guilt-prone people were more likely than others both to opt to be paid on their
performance alone (Studies 1, 3, 4, and 5) and to opt to be paid on the basis of
the average of their performance and that of others whose competence was more
similar to their own (Studies 2 and 5). Guilt proneness did not predict people's
willingness to form outcome-interdependent relationships with potential partners
who lacked domain-specific expertise (Studies 4 and 5). It also did not predict
people's willingness to form relationships when poor individual performance would
not negatively affect partner outcomes (Study 4). Guilt proneness therefore
predicts whether, and with whom, people develop interdependent relationships. The
findings also demonstrate that highly guilt-prone people sacrifice financial gain
out of concern about how their actions would influence others' welfare. As such,
the findings demonstrate a novel way in which guilt proneness limits free-riding
and therefore reduces the incidence of potentially unethical behavior. Lastly,
the findings demonstrate that people who lack competence may not always seek out
competence in others when choosing partners.
PMID- 25133717
TI - Sense of control under uncertainty depends on people's childhood environment: a
life history theory approach.
AB - Past research found that environmental uncertainty leads people to behave
differently depending on their childhood environment. For example, economic
uncertainty leads people from poor childhoods to become more impulsive while
leading people from wealthy childhoods to become less impulsive. Drawing on life
history theory, we examine the psychological mechanism driving such diverging
responses to uncertainty. Five experiments show that uncertainty alters people's
sense of control over the environment. Exposure to uncertainty led people from
poorer childhoods to have a significantly lower sense of control than those from
wealthier childhoods. In addition, perceptions of control statistically mediated
the effect of uncertainty on impulsive behavior. These studies contribute by
demonstrating that sense of control is a psychological driver of behaviors
associated with fast and slow life history strategies. We discuss the
implications of this for theory and future research, including that environmental
uncertainty might lead people who grew up poor to quit challenging tasks sooner
than people who grew up wealthy.
PMID- 25133719
TI - Accuracy and bias in self-perceptions of responsive behavior: implications for
security in romantic relationships.
AB - The current research examined self-perception of responsive behavior as a process
through which perceivers who highly value romantic partners generate security
that they are valued by those partners. People hold naive theories that their
responsive behavior elicits positive sentiments from others, such as
satisfaction, positive regard, and commitment, and they believe their
unresponsive behavior elicits negative sentiments. Accordingly, 2 dyadic
behavioral observation studies, one involving conflict interactions (Study 1) and
one involving support interactions (Study 2), suggested that people who value
partners achieve security that they are valued by their partners through both
accurate and biased self-perceptions of responsive behavior. Perceivers who
valued partners accurately perceived their more responsive behavior enacted
toward partners, which bolstered their confidence that they were valued by
partners (accurate self-perception). In addition, perceivers who valued partners
had biased and exaggerated perceptions of their own responsive behavior, which
also bolstered their perceptions of being valued by partners (biased self
perception). Examination of memories of responsive behavior 2 weeks and 6 months
following interactions (Study 2) suggested that perceivers' memories of their own
responsive behavior derived from a mix of accuracy and bias, which predicted
changes in relationship security over time. These findings underscore the
importance of perceivers' representations of their responsive behavior, both
accurate and biased, as determinants of their own relationship security.
PMID- 25133720
TI - Mean-level personality development across childhood and adolescence: a temporary
defiance of the maturity principle and bidirectional associations with parenting.
AB - In this study, we investigated mean-level personality development in children
from 6 to 20 years of age. Additionally, we investigated longitudinal,
bidirectional associations between child personality and maternal overreactive
and warm parenting. In this 5-wave study, mothers reported on their child's
personality from Time 1 (T1) through Time 4 (T4), and children provided self
reports from Time 2 (T2) through Time 5 (T5). Mothers reported on their levels of
overreactive and warm parenting from T2 through T4. Using cohort-sequential
latent growth curve modeling, we investigated mother reported child personality
from 6 to 17 years of age and child reported personality from 9 to 20 years of
age. Extraversion decreased linearly across the entire study. Benevolence and
conscientiousness increased from middle to late childhood, temporarily declined
from late childhood to mid-adolescence, and increased again thereafter.
Imagination decreased from middle childhood to mid-adolescence and also increased
thereafter. Mothers reported a temporary decline in emotional stability with an
increase thereafter, whereas children did not. Boys and girls differed in mean
levels of the personality dimensions and, to a lesser extent, in the degree and
direction of changes. Latent difference score modeling showed that child
personality predicted changes in parenting and that, to a lesser extent,
parenting predicted changes in child traits. Additionally, changes in child
personality were associated with changes in maternal parenting. Results of the
present study show that personality change is not directed at increasing maturity
from childhood to mid-adolescence and that it elicits and is shaped by both
positive and negative parenting.
PMID- 25133721
TI - How group-based emotions are shaped by collective emotions: evidence for
emotional transfer and emotional burden.
AB - Extensive research has established the pivotal role that group-based emotions
play in shaping intergroup processes. The underlying implicit assumption in
previous work has been that these emotions reflect what the rest of the group
feels (i.e., collective emotions). However, one can experience an emotion in the
name of her or his group, which is inconsistent with what the collective feels.
The current research investigated this phenomenon of emotional nonconformity.
Particularly, we proposed that when a certain emotional reaction is perceived as
appropriate, but the collective is perceived as not experiencing this emotion,
people would experience stronger levels of group-based emotion, placing their
emotional experience farther away from that of the collective. We provided
evidence for this process across 2 different emotions: group-based guilt and
group-based anger (Studies 1 and 2) and across different intergroup contexts
(Israeli-Palestinian relations in Israel, and Black-White relations in the United
States). In Studies 3 and 4, we demonstrate that this process is moderated by the
perceived appropriateness of the collective emotional response. Studies 4 and 5
further provided evidence for the mechanisms underlying this effect, pointing to
a process of emotional burden (i.e., feeling responsible for carrying the emotion
in the name of the group) and of emotional transfer (i.e., transferring negative
feelings one has toward the ingroup, toward the event itself). This work brings
to light processes that were yet to be studied regarding the relationship between
group members, their perception of their group, and the emotional processes that
connect them.
PMID- 25133722
TI - Evidence for the social role theory of stereotype content: observations of
groups' roles shape stereotypes.
AB - In applying social role theory to account for the content of a wide range of
stereotypes, this research tests the proposition that observations of groups'
roles determine stereotype content (Eagly & Wood, 2012). In a novel test of how
stereotypes can develop from observations, preliminary research collected
participants' beliefs about the occupational roles (e.g., lawyer, teacher, fast
food worker, chief executive officer, store clerk, manager) in which members of
social groups (e.g., Black women, Hispanics, White men, the rich, senior
citizens, high school dropouts) are overrepresented relative to their numbers in
the general population. These beliefs about groups' typical occupational roles
proved to be generally accurate when evaluated in relation to data from the
Bureau of Labor Statistics. Then, correlational studies predicted participants'
stereotypes of social groups from the attributes ascribed to group members'
typical occupational roles (Studies 1a, 1b, and 1c), the behaviors associated
with those roles (Study 2), and the occupational interest profile of the roles
(Study 3). As predicted by social role theory, beliefs about the attributes of
groups' typical roles were strongly related to group stereotypes on both
communion and agency/competence. In addition, an experimental study (Study 4)
demonstrated that when social groups were described with changes to their typical
social roles in the future, their projected stereotypes were more influenced by
these future roles than by their current group stereotypes, thus supporting
social role theory's predictions about stereotype change. Discussion considers
the implications of these findings for stereotype change and the relation of
social role theory to other theories of stereotype content.
PMID- 25133723
TI - Selfish or selfless? On the signal value of emotion in altruistic behavior.
AB - Theories that reject the existence of altruism presume that emotional benefits
serve as ulterior motives for doing good deeds. These theories argue that even in
the absence of material and reputational benefits, individuals reap utility from
the feelings associated with doing good. In response to this normative view of
altruism, this article examines the descriptive question of whether laypeople
penalize emotional prosocial actors. Six studies find that emotion serves as a
positive signal of moral character, despite the intrapsychic benefits associated
with it. This is true when emotion motivates prosocial behavior (Studies 1, 2, 3,
and 5) and when emotion is a positive outcome of prosocial behavior (i.e., "warm
glow"; Studies 4, 5, and 6). Emotional actors are considered to be moral because
people believe emotion provides an honest and direct signal that the actor feels
a genuine concern for others. Consequently, prosocial actors who are motivated by
the expectation of emotional rewards are judged differently than prosocial actors
who are motivated by other benefits, such as reputational or material rewards
(Study 6). These results suggest that laypeople do not view altruism as
incompatible with all benefits to the self.
PMID- 25133725
TI - Religious magnanimity: reminding people of their religious belief system reduces
hostility after threat.
AB - The present research tested the hypothesis that many people's ambient religious
beliefs are non-hostile and magnanimous by assessing whether reminding people of
their religious belief systems would reduce hostility after threat. Across
religious affiliations, participants reported that their religious belief systems
encourage magnanimous behavior. In addition, priming their religious belief
systems caused them to act more magnanimously, but only when motivated to adhere
to salient ideals (i.e., after threats; see Gailliot, Stillman, Schmeichel,
Maner, & Plant, 2008; Jonas et al., 2008). Specifically, in Studies 1-5, we found
that a general religious belief system prime ("Which religious belief system do
you identify with?") reduced the hostility of people's thoughts, behaviors, and
judgments following threat. In Studies 6 and 7, we found that the religious
belief system prime only reduced hostile reactions to threat among participants
who held religious beliefs that oriented them toward magnanimous ideals (Study 6)
and who were dispositionally inclined to adhere to their ideals (Study 7). In
Study 8, we found support for the role of magnanimous ideals by demonstrating
that directly priming these ideals yielded effects similar to those produced by a
religious belief system prime. These studies provide consistent evidence that, by
invoking magnanimous ideals, a religious belief system prime promotes less
hostile responses to threat.
PMID- 25133724
TI - Paying more when paying for others.
AB - Social behavior is heavily influenced by the perception of the behaviors of
others. We considered how perceptions (and misperceptions) of kindness can
increase generosity in economic transactions. We investigated how these
perceptions can alter behavior in a novel real-life situation that pitted
kindness against selfishness. That situation, consumer elective pricing, is
defined by an economic transaction allowing people to purchase goods or services
for any price (including zero). Field and lab experiments compared how people
behave in 2 financially identical circumstances: pay-what-you-want (in which
people are ostensibly paying for themselves) and pay-it-forward (in which people
are ostensibly paying on behalf of someone else). In 4 field experiments, people
paid more under pay-it-forward than pay-what-you-want (Studies 1-4). Four
subsequent lab studies assessed whether the salience of others explains the
increased payments (Study 5), whether ability to justify lowered payments (Study
6), and whether the manipulation was operating through changing the perceptions
of others (Studies 7 and 8). When people rely on ambiguous perceptions, pay-it
forward leads to overestimating the kindness of others and a corresponding
increase in personal payment. When those perceptions are replaced with explicit
descriptive norms (i.e., others' payment amounts), that effect is eliminated.
Finally, subsequent studies confirmed that the effects were not driven by
participant confusion (Studies 9A and 9B) and not limited by the specificity of
the referent other in the pay-it-forward framing (Study 9C).
PMID- 25133726
TI - The involuntary excluder effect: those included by an excluder are seen as
exclusive themselves.
AB - People are highly vigilant for and alarmed by social exclusion. Previous research
has focused largely on the emotional and motivational consequences of being
unambiguously excluded by others. The present research instead examines how
people make sense of a more ambiguous dynamic, 1-person exclusion--situations in
which one person (the excluder) excludes someone (the rejected) while including
someone else (the included). Using different methodological paradigms, converging
outcome measures, and complementary comparison standards, 5 studies present
evidence of an involuntary excluder effect: Social perceivers are quick to see
included persons as though they are excluders themselves. Included individuals
are seen as belonging to an exclusive alliance with the excluder, as liking the
excluder more than the rejected, and as likely to perpetuate future exclusion
against the rejected. Behavioral evidence reinforced these findings: The included
was approached with caution and suspicion. Notably, such perceptions of the
included as an excluder were drawn by the rejected themselves and outside
observers alike, did not reflect the attitudes and intentions of included persons
or those who simulated 1-person exclusion from the vantage point of the included,
applied specifically to the included (but not someone who simply witnessed the
rejected's rejection), and arose as a consequence of intentional acts of
exclusion (and thus, not just because 2 individuals shared an exclusive
experience). Consistencies with and contributions to literatures on balance
theory, minimal groups, group entitativity, and the ostracism detection system
literatures are discussed.
PMID- 25133727
TI - Addressing the empathy deficit: beliefs about the malleability of empathy predict
effortful responses when empathy is challenging.
AB - Empathy is often thought to occur automatically. Yet, empathy frequently breaks
down when it is difficult or distressing to relate to people in need, suggesting
that empathy is often not felt reflexively. Indeed, the United States as a whole
is said to be displaying an empathy deficit. When and why does empathy break
down, and what predicts whether people will exert effort to experience empathy in
challenging contexts? Across 7 studies, we found that people who held a malleable
mindset about empathy (believing empathy can be developed) expended greater
empathic effort in challenging contexts than did people who held a fixed theory
(believing empathy cannot be developed). Specifically, a malleable theory of
empathy--whether measured or experimentally induced--promoted (a) more self
reported effort to feel empathy when it is challenging (Study 1); (b) more
empathically effortful responses to a person with conflicting views on personally
important sociopolitical issues (Studies 2-4); (c) more time spent listening to
the emotional personal story of a racial outgroup member (Study 5); and (d)
greater willingness to help cancer patients in effortful, face-to-face ways
(Study 6). Study 7 revealed a possible reason for this greater empathic effort in
challenging contexts: a stronger interest in improving one's empathy. Together,
these data suggest that people's mindsets powerfully affect whether they exert
effort to empathize when it is needed most, and these data may represent a point
of leverage in increasing empathic behaviors on a broad scale.
PMID- 25133728
TI - The psychology of martyrdom: making the ultimate sacrifice in the name of a
cause.
AB - Martyrdom is defined as the psychological readiness to suffer and sacrifice one's
life for a cause. An integrative set of 8 studies investigated the concept of
martyrdom by creating a new tool to quantitatively assess individuals' propensity
toward self-sacrifice. Studies 1A-1C consisted of psychometric work attesting to
the scale's unidimensionality, internal consistency, and temporal stability while
examining its nomological network. Studies 2A-2B focused on the scale's
predictive validity, especially as it relates to extreme behaviors and suicidal
terrorism. Studies 3-5 focused on the influence of self-sacrifice on automatic
decision making, costly and altruistic behaviors, and morality judgments. Results
involving more than 2,900 participants from different populations, including a
terrorist sample, supported the proposed conceptualization of martyrdom and
demonstrated its importance for a vast repertoire of cognitive, emotional, and
behavioral phenomena. Implications and future directions for the psychology of
terrorism are discussed.
PMID- 25133729
TI - You are so beautiful... to me: seeing beyond biases and achieving accuracy in
romantic relationships.
AB - Do romantic partners see each other realistically, or do they have overly
positive perceptions of each other? Research has shown that realism and
positivity co-exist in romantic partners' perceptions (Boyes & Fletcher, 2007).
The current study takes a novel approach to explaining this seemingly paradoxical
effect when it comes to physical attractiveness--a highly evaluative trait that
is especially relevant to romantic relationships. Specifically, we argue that
people are aware that others do not see their partners as positively as they do.
Using both mean differences and correlational approaches, we test the hypothesis
that despite their own biased and idiosyncratic perceptions, people have 2 types
of partner-knowledge: insight into how their partners see themselves (i.e.,
identity accuracy) and insight into how others see their partners (i.e.,
reputation accuracy). Our results suggest that romantic partners have some
awareness of each other's identity and reputation for physical attractiveness,
supporting theories that couple members' perceptions are driven by motives to
fulfill both esteem- and epistemic-related needs (i.e., to see their partners
positively and realistically).
PMID- 25133730
TI - On the consistency of personality types across adulthood: latent profile analyses
in two large-scale panel studies.
AB - Consistency and change in personality were analyzed by examining personality
types across adulthood and old age using data from 2 nationally representative
panel studies from Germany (N = 14,718; 16-82 years) and Australia (N = 8,315; 15
79 years). In both samples, the Big Five personality traits were measured twice
across a period of 4 years. Latent profile analyses and latent profile transition
analyses revealed 4 main findings: First, solutions with 3 (in the German sample)
or 4 (in the Australian sample) personality types were found to be most
interpretable. Second, measurement invariance tests revealed that these
personality types were consistent across all age groups but differed slightly
between men and women. Third, age was related to the number of individuals
classified within each personality type. Namely, there were more resilients and
fewer undercontrollers in older compared with younger age groups. Fourth, there
was strong consistency of personality type membership across a period of 4 years
in both genders and most age cohorts. Comparatively less consistency across time
was found for undercontrollers and individuals in old age. Taken together, these
findings show that in the 2 nations studied here, personality types were highly
consistent across gender, age, and time.
PMID- 25133731
TI - A general synthesis of ynones from aldehydes via oxidative C-C bond cleavage
under aerobic conditions.
AB - We describe a direct synthesis of various ynones from readily available aldehydes
and hypervalent alkynyl iodides. In this method, a gold catalyst and a secondary
amine work synergistically to produce the trisubstituted allenyl aldehyde, which
can be converted to the desired ynone through an in situ C-C bond oxidative
cleavage using molecular oxygen.
PMID- 25133732
TI - Metabolic engineering of Saccharomyces cerevisiae for caffeine and theobromine
production.
AB - Caffeine (1, 3, 7-trimethylxanthine) and theobromine (3, 7-dimethylxanthine) are
the major purine alkaloids in plants, e.g., tea (Camellia sinensis) and coffee
(Coffea arabica). Caffeine is a major component of coffee and is used widely in
food and beverage industries. Most of the enzymes involved in the caffeine
biosynthetic pathway have been reported previously. Here, we demonstrated the
biosynthesis of caffeine (0.38 mg/L) by co-expression of Coffea arabica
xanthosine methyltransferase (CaXMT) and Camellia sinensis caffeine synthase
(TCS) in Saccharomyces cerevisiae. Furthermore, we endeavored to develop this
production platform for making other purine-based alkaloids. To increase the
catalytic activity of TCS in an effort to increase theobromine production, we
identified four amino acid residues based on structural analyses of 3D-model of
TCS. Two TCS1 mutants (Val317Met and Phe217Trp) slightly increased in theobromine
accumulation and simultaneously decreased in caffeine production. The application
and further optimization of this biosynthetic platform are discussed.
PMID- 25133733
TI - Deprived TLR9 expression in apparently healthy nasal mucosa might trigger polyp
growth in chronic rhinosinusitis patients.
AB - BACKGROUND: The origin of nasal polyps in chronic rhinosinusitis is unknown, but
the role of viral infections in polyp growth is clinically well established. Toll
like receptors (TLRs) have recently emerged as key players in our local airway
defense against microbes. Among these, TLR9 has gained special interest in viral
diseases. Many studies on chronic rhinosinusitis with nasal polyps (CRSwNP)
compare polyp tissue with nasal mucosa from polyp-free individuals. Knowledge
about changes in the turbinate tissue bordering the polyp tissue is limited.
OBJECTIVES: To analyse the role of TLR9 mediated microbial defense in tissue
bordering the polyp. METHODS: Nasal polyps and turbinate tissue from 11 patients
with CRSwNP and turbinate tissue from 11 healthy controls in total were used.
Five biopsies from either group were analysed immediately with flow cytometry
regarding receptor expression and 6 biopsies were used for in vitro stimulation
with a TLR9 agonist, CpG. Cytokine release was analysed using Luminex. Eight
patients with CRSwNP in total were intranasally challenged with CpG/placebo 24
hours before surgery and the biopsies were collected and analysed as above.
RESULTS: TLR9 expression was detected on turbinate epithelial cells from healthy
controls and polyp epithelial cells from patients, whereas TLR9 was absent in
turbinate epithelial cells from patients. CpG stimulation increased the
percentage cells expressing TLR9 and decreased percentage cells expressing VEGFR2
in turbinate tissue from patients. After CpG stimulation the elevated levels of
IL-6, G-CSF and MIP-1beta in the turbinate tissue from patients were reduced
towards the levels demonstrated in healthy controls. CONCLUSION: Defects in the
TLR9 mediated microbial defense in the mucosa adjacent to the anatomic origin of
the polyp might explain virus induced polyp growth. CpG stimulation decreased
VEGFR2, suggesting a role for CpG in polyp formation. The focus on turbinate
tissue in patients with CRSwNP opens new perspectives in CRSwNP-research.
PMID- 25133738
TI - Elevated levels of circulating DNA in cardiovascular disease patients:
metagenomic profiling of microbiome in the circulation.
AB - Cardiovascular diseases (CVDs) are the leading cause of death worldwide. An
expanding body of evidence supports the role of human microbiome in the
establishment of CVDs and, this has gained much attention recently. This work was
aimed to study the circulating human microbiome in CVD patients and healthy
subjects. The levels of circulating cell free DNA (circDNA) was higher in CVD
patients (n = 80) than in healthy controls (n = 40). More specifically, the
relative levels of circulating bacterial DNA and the ratio of 16S rRNA/beta
globin gene copy numbers were higher in the circulation of CVD patients than
healthy individuals. In addition, we found a higher circulating microbial
diversity in CVD patients (n = 3) in comparison to healthy individuals (n = 3) by
deep shotgun sequencing. At the phylum level, we observed a dominance of
Actinobacteria in CVD patients, followed by Proteobacteria, in contrast to that
in healthy controls, where Proteobacteria was predominantly enriched, followed by
Actinobacteria. The circulating virome in CVD patients was enriched with
bacteriophages with a preponderance of Propionibacterium phages, followed by
Pseudomonas phages and Rhizobium phages in contrast to that in healthy
individuals, where a relatively greater abundance of eukaryotic viruses dominated
by Lymphocystis virus (LCV) and Torque Teno viruses (TTV) was observed. Thus, the
release of bacterial and viral DNA elements in the circulation could play a major
role leading to elevated circDNA levels in CVD patients. The increased circDNA
levels could be either the cause or consequence of CVD incidence, which needs to
be explored further.
PMID- 25133740
TI - Nanodrug-enhanced radiofrequency tumor ablation: effect of micellar or liposomal
carrier on drug delivery and treatment efficacy.
AB - PURPOSE: To determine the effect of different drug-loaded nanocarriers (micelles
and liposomes) on delivery and treatment efficacy for radiofrequency ablation
(RFA) combined with nanodrugs. MATERIALS/METHODS: Fischer 344 rats were used (n =
196). First, single subcutaneous R3230 tumors or normal liver underwent RFA
followed by immediate administration of i.v. fluorescent beads (20, 100, and 500
nm), with fluorescent intensity measured at 4-24 hr. Next, to study carrier type
on drug efficiency, RFA was combined with micellar (20 nm) or liposomal (100 nm)
preparations of doxorubicin (Dox; targeting HIF-1alpha) or quercetin (Qu;
targeting HSP70). Animals received RFA alone, RFA with Lipo-Dox or Mic-Dox (1 mg
i.v., 15 min post-RFA), and RFA with Lipo-Qu or Mic-Qu given 24 hr pre- or 15 min
post-RFA (0.3 mg i.v.). Tumor coagulation and HIF-1alpha or HSP70 expression were
assessed 24 hr post-RFA. Third, the effect of RFA combined with i.v. Lipo-Dox,
Mic-Dox, Lipo-Qu, or Mic-Qu (15 min post-RFA) compared to RFA alone on tumor
growth and animal endpoint survival was evaluated. Finally, drug uptake was
compared between RFA/Lipo-Dox and RFA/Mic-Dox at 4-72 hr. RESULTS: Smaller 20 nm
beads had greater deposition and deeper tissue penetration in both tumor (100
nm/500 nm) and liver (100 nm) (p<0.05). Mic-Dox and Mic-Qu suppressed
periablational HIF-1alpha or HSP70 rim thickness more than liposomal preparations
(p<0.05). RFA/Mic-Dox had greater early (4 hr) intratumoral doxorubicin, but
RFA/Lipo-Dox had progressively higher intratumoral doxorubicin at 24-72 hr post
RFA (p<0.04). No difference in tumor growth and survival was seen between
RFA/Lipo-Qu and RFA/Mic-Qu. Yet, RFA/Lipo-Dox led to greater animal endpoint
survival compared to RFA/Mic-Dox (p<0.03). CONCLUSION: With RF ablation, smaller
particle micelles have superior penetration and more effective local molecular
modulation. However, larger long-circulating liposomal carriers can result in
greater intratumoral drug accumulation over time and reduced tumor growth.
Accordingly, different carriers provide specific advantages, which should be
considered when formulating optimal combination therapies.
PMID- 25133742
TI - Prediction of chemical biodegradability using support vector classifier optimized
with differential evolution.
AB - Reliable computer models for the prediction of chemical biodegradability from
molecular descriptors and fingerprints are very important for making health and
environmental decisions. Coupling of the differential evolution (DE) algorithm
with the support vector classifier (SVC) in order to optimize the main parameters
of the classifier resulted in an improved classifier called the DE-SVC, which is
introduced in this paper for use in chemical biodegradability studies. The DE-SVC
was applied to predict the biodegradation of chemicals on the basis of extensive
sample data sets and known structural features of molecules. Our optimization
experiments showed that DE can efficiently find the proper parameters of the SVC.
The resulting classifier possesses strong robustness and reliability compared
with grid search, genetic algorithm, and particle swarm optimization methods. The
classification experiments conducted here showed that the DE-SVC exhibits better
classification performance than models previously used for such studies. It is a
more effective and efficient prediction model for chemical biodegradability.
PMID- 25133741
TI - Mice in Bion-M 1 space mission: training and selection.
AB - After a 16-year hiatus, Russia has resumed its program of biomedical research in
space, with the successful 30-day flight of the Bion-M 1 biosatellite (April 19
May 19, 2013). The principal species for biomedical research in this project was
the mouse. This paper presents an overview of the scientific goals, the
experimental design and the mouse training/selection program. The aim of mice
experiments in the Bion-M 1 project was to elucidate cellular and molecular
mechanisms, underlying the adaptation of key physiological systems to long-term
exposure in microgravity. The studies with mice combined in vivo measurements,
both in flight and post-flight (including continuous blood pressure measurement),
with extensive in vitro studies carried out shortly after return of the mice and
in the end of recovery study. Male C57/BL6 mice group housed in space habitats
were flown aboard the Bion-M 1 biosatellite, or remained on ground in the control
experiment that replicated environmental and housing conditions in the
spacecraft. Vivarium control groups were used to account for housing effects and
possible seasonal differences. Mice training included the co-adaptation in
housing groups and mice adaptation to paste food diet. The measures taken to co
adapt aggressive male mice in housing groups and the peculiarities of "space"
paste food are described. The training program for mice designated for in vivo
studies was broader and included behavioral/functional test battery and
continuous behavioral measurements in the home-cage. The results of the
preliminary tests were used for the selection of homogenous groups. After the
flight, mice were in good condition for biomedical studies and displayed signs of
pronounced disadaptation to Earth's gravity. The outcomes of the training program
for the mice welfare are discussed. We conclude that our training program was
effective and that male mice can be successfully employed in space biomedical
research.
PMID- 25133743
TI - Hyperspectral reflected light microscopy of plasmonic Au/Ag alloy nanoparticles
incubated as multiplex chromatic biomarkers with cancer cells.
AB - A hyperspectral microscopy system based on a reflected light method for plasmonic
nanoparticle (NP) imaging was designed and compared with a conventional darkfield
method for spatial localization and spectroscopic identification of single Au, Ag
and Au/Ag alloy NPs incubated with fixed human cancer cell preparations. A new
synthesis protocol based on co-reduction of Au and Ag salts combined with the
seeded growth technique was used for the fabrication of monodispersed alloy NPs
with sizes ranging from 30 to 100 nm in diameter. We validated theoretically and
experimentally the performance of 60 nm Au, Ag and Au/Ag (50 : 50) NPs as
multiplexed biological chromatic markers for biomedical diagnostics and optical
biosensing. The advantages of the proposed reflected light microscopy method are
presented for NP imaging in a complex and highly diffusing medium such as a
cellular environment. The obtained information is essential for the development
of a high throughput, selective and efficient strategy for cancer detection and
treatment.
PMID- 25133744
TI - Nonstoichiometric perovskite CaMnO(3-delta) for oxygen electrocatalysis with high
activity.
AB - Perovskite oxides offer efficient and cheap electrocatalysts for both oxygen
reduction reactions and oxygen evolution reactions (ORR/OER) in diverse oxygen
based electrochemical technologies. In this study, we report a facile strategy to
enhance the electrocatalytic activity of CaMnO3 by introducing oxygen defects.
The nonstoichiometric CaMnO(3-delta) (0 < delta <= 0.5) was prepared through
thermal reduction of pristine perovskite microspheres and nanoparticles, which
were synthesized from thermal-decomposition of carbonate precursors and the
Pechini route, respectively. The as-prepared samples were analyzed by chemical
titration, structural refinement, thermogravimetric analysis, and energy
spectrometry. In 0.1 M KOH aqueous solution, the nonstoichiometric CaMnO(3-delta)
with delta near 0.25 and an average Mn valence close to 3.5 exhibited the highest
ORR activity (36.7 A g(-1) at 0.70 V vs RHE, with onset potential of 0.96 V),
which is comparable to that of benchmark Pt/C. Density functional theory (DFT)
studies and electrical conductivity measurement revealed that the enhanced ORR
kinetics is due to facilitated oxygen activation and improved electrical
properties. Besides high activity, the nonstoichiometric perovskite oxides showed
respectable catalytic stability. Furthermore, the moderate oxygen-defective
CaMnO(3-delta) (delta ~ 0.25) favored the OER because of the improved electrical
conductivity. This study makes nonstoichiometric CaMnO(3-delta) a promising
active, inexpensive bifunctional catalytic material for reversible ORR and OER.
PMID- 25133745
TI - A highly selective sulfinate ester probe for thiol bioimaging.
AB - We describe here hitherto unexplored chemistry of the sulfinate ester functional
group as being highly selective towards nucleophilic substitution by thiols at
physiological pH. Using this cleavable trigger, an optical thiol probe that is
suitable for thiol bioimaging has been developed.
PMID- 25133746
TI - Cancer screening rates in individuals with different life expectancies.
AB - IMPORTANCE: Routine cancer screening has unproven net benefit for patients with
limited life expectancy. OBJECTIVE: To examine the patterns of prostate, breast,
cervical, and colorectal cancer screening in the United States in individuals
with different life expectancies. DESIGN, SETTING, AND PARTICIPANTS: Data from
the population-based National Health Interview Survey (NHIS) from 2000 through
2010 were used and included 27 404 participants aged 65 years or older. Using a
validated mortality index specific for NHIS, participants were grouped into those
with low (<25%), intermediate (25%-49%), high (50%-74%), and very high (>=75%)
risks of 9-year mortality. MAIN OUTCOMES AND MEASURES: Rates of prostate, breast,
cervical, and colorectal cancer screening. RESULTS: In participants with very
high mortality risk, 31% to 55% received recent cancer screening, with prostate
cancer screening being most common (55%). For women who had a hysterectomy for
benign reasons, 34% to 56% had a Papanicolaou test within the past 3 years. On
multivariate analysis, very high vs low mortality risk was associated with less
screening for prostate (odds ratio [OR], 0.65 [95% CI, 0.50-0.85]), breast (OR,
0.43 [95% CI, 0.35-0.53]), and cervical (OR, 0.50 [95% CI, 0.36-0.70]) cancers.
There was less screening for prostate and cervical cancers in more recent years
compared with 2000, and there was no significant interaction between calendar
year and mortality risk for any cancer screening (P > .05 for all cancers). Our
sensitivity analysis showed that screening was also common in individuals with
less than 5-year life expectancy. CONCLUSIONS AND RELEVANCE: A substantial
proportion of the US population with limited life expectancy received prostate,
breast, cervical, and colorectal cancer screening that is unlikely to provide net
benefit. These results suggest that overscreening is common in both men and
women, which not only increases health care expenditure but can lead to net
patient harm.
PMID- 25133747
TI - Genome-wide prediction of the polymorphic Ser gene family in Tetrahymena
thermophila based on motif analysis.
AB - Even though antigenic variation is employed among parasitic protozoa for host
immune evasion, Tetrahymena thermophila, a free-living ciliate, can also change
its surface protein antigens. These cysteine-rich glycosylphosphatidylinositol
(GPI)-linked surface proteins are encoded by a family of polymorphic Ser genes.
Despite the availability of T. thermophila genome, a comprehensive analysis of
the Ser family is limited by its high degree of polymorphism. In order to
overcome this problem, a new approach was adopted by searching for Ser candidates
with common motif sequences, namely length-specific repetitive cysteine pattern
and GPI anchor site. The candidate genes were phylogenetically compared with the
previously identified Ser genes and classified into subtypes. Ser candidates were
often found to be located as tandem arrays of the same subtypes on several
chromosomal scaffolds. Certain Ser candidates located in the same chromosomal
arrays were transcriptionally expressed at specific T. thermophila developmental
stages. These Ser candidates selected by the motif analysis approach can form the
foundation for a systematic identification of the entire Ser gene family, which
will contribute to the understanding of their function and the basis of T.
thermophila antigenic variation.
PMID- 25133748
TI - Effect of sodium chloride on hydration structures of PMEA and P(MPC-r-BMA).
AB - The hydration structures of two different types of biomaterials, i.e., poly(2
methoxyethyl acrylate) (PMEA) and a random copolymer of 2-methacryloyloxyethyl
phosphorylcholine and n-butyl methacrylate (P(MPC-r-BMA)), were investigated by
means of attenuated total reflection infrared (ATR-IR) spectroscopy. The effects
of the addition of sodium chloride to liquid water in contact with the surfaces
of the polymer films were examined. The neutral polymer of PMEA was easily
dehydrated by NaCl addition, whereas the zwitterionic polymer of P(MPC-r-BMA) was
hardly dehydrated. More specifically, nonfreezing water having a strong
interaction with the PMEA chain and freezing bound water having an intermediate
interaction were hardly dehydrated by contacting with normal saline solution,
whereas freezing water having a weak interaction with the PMEA chain was readily
dehydrated. In contrast, freezing water in P(MPC-r-BMA) is exchanged for the
saline solution contacting with the material surface without dehydration.
PMID- 25133749
TI - Long-term disease dynamics for a specialized parasite of ant societies: a field
study.
AB - Many studies have investigated how social insects behave when a parasite is
introduced into their colonies. These studies have been conducted in the
laboratory, and we still have a limited understanding of the dynamics of ant
parasite interactions under natural conditions. Here we consider a specialized
parasite of ant societies (Ophiocordyceps camponoti-rufipedis infecting
Camponotus rufipes) within a rainforest. We first established that the parasite
is unable to develop to transmission stage when introduced within the host nest.
Secondly, we surveyed all colonies in the studied area and recorded 100%
prevalence at the colony level (all colonies were infected). Finally, we
conducted a long-term detailed census of parasite pressure, by mapping the
position of infected dead ants and foraging trails (future hosts) in the
immediate vicinity of the colonies over 20 months. We report new dead infected
ants for all the months we conducted the census--at an average of 14.5
cadavers/month/colony. Based on the low infection rate, the absence of colony
collapse or complete recovery of the colonies, we suggest that this parasite
represents a chronic infection in the ant societies. We also proposed a "terminal
host model of transmission" that links the age-related polyethism to the
persistence of a parasitic infection.
PMID- 25133750
TI - Activity Patterns of Preschool-Aged Children at Risk for Obesity.
AB - BACKGROUND: Although the prevalence of obesity in young children highlights the
importance of early interventions to promote physical activity (PA), there are
limited data on activity patterns in this age group. The purpose of this study
was to describe activity patterns in preschool-aged children and explore
differences by weight status. METHODS: Analyses use baseline data from Healthy
Homes/Healthy Kids-Preschool, a pilot obesity prevention trial of preschool-aged
children who are overweight or at risk for being overweight. A modified parent
reported version of the previous-day PA recall was used to summarize types of
activity. Accelerometry was used to summarize daily and hourly activity patterns.
RESULTS: "Playing with toys" accounted for the largest proportion of a child's
previous day, followed by "meals and snacks" and "chores." Accelerometry-measured
daily time spent in sedentary behavior, light PA, and moderate-to-vigorous PA
(MVPA) was 412, 247, and 69 minutes, respectively. Percentage of hourly time
spent in MVPA ranged from 3% to 13%, peaking in the late morning and evening
hours. There were no statistically significant MVPA differences by weight status.
CONCLUSIONS: This study extends our understanding of activity types, amounts, and
patterns in preschool-aged children and warrants further exploration of
differences in PA patterns by weight status.
PMID- 25133751
TI - Mutation screening of retinal dystrophy patients by targeted capture from tagged
pooled DNAs and next generation sequencing.
AB - PURPOSE: Retinal dystrophies are genetically heterogeneous, resulting from
mutations in over 200 genes. Prior to the development of massively parallel
sequencing, comprehensive genetic screening was unobtainable for most patients.
Identifying the causative genetic mutation facilitates genetic counselling,
carrier testing and prenatal/pre-implantation diagnosis, and often leads to a
clearer prognosis. In addition, in a proportion of cases, when the mutation is
known treatment can be optimised and patients are eligible for enrolment into
clinical trials for gene-specific therapies. METHODS: Patient genomic DNA was
sheared, tagged and pooled in batches of four samples, prior to targeted capture
and next generation sequencing. The enrichment reagent was designed against genes
listed on the RetNet database (July 2010). Sequence data were aligned to the
human genome and variants were filtered to identify potential pathogenic
mutations. These were confirmed by Sanger sequencing. RESULTS: Molecular analysis
of 20 DNAs from retinal dystrophy patients identified likely pathogenic mutations
in 12 cases, many of them known and/or confirmed by segregation. These included
previously described mutations in ABCA4 (c.6088C>T,p.R2030*; c.5882G>A,p.G1961E),
BBS2 (c.1895G>C,p.R632P), GUCY2D (c.2512C>T,p.R838C), PROM1 (c.1117C>T,p.R373C),
RDH12 (c.601T>C,p.C201R; c.506G>A,p.R169Q), RPGRIP1 (c.3565C>T,p.R1189*) and
SPATA7 (c.253C>T,p.R85*) and new mutations in ABCA4 (c.3328+1G>C), CRB1
(c.2832_2842+23del), RP2 (c.884-1G>T) and USH2A (c.12874A>G,p.N4292D).
CONCLUSIONS: Tagging and pooling DNA prior to targeted capture of known retinal
dystrophy genes identified mutations in 60% of cases. This relatively high
success rate may reflect enrichment for consanguineous cases in the local
Yorkshire population, and the use of multiplex families. Nevertheless this is a
promising high throughput approach to retinal dystrophy diagnostics.
PMID- 25133752
TI - Relative accuracy evaluation.
AB - The quality of data plays an important role in business analysis and decision
making, and data accuracy is an important aspect in data quality. Thus one
necessary task for data quality management is to evaluate the accuracy of the
data. And in order to solve the problem that the accuracy of the whole data set
is low while a useful part may be high, it is also necessary to evaluate the
accuracy of the query results, called relative accuracy. However, as far as we
know, neither measure nor effective methods for the accuracy evaluation methods
are proposed. Motivated by this, for relative accuracy evaluation, we propose a
systematic method. We design a relative accuracy evaluation framework for
relational databases based on a new metric to measure the accuracy using
statistics. We apply the methods to evaluate the precision and recall of basic
queries, which show the result's relative accuracy. We also propose the method to
handle data update and to improve accuracy evaluation using functional
dependencies. Extensive experimental results show the effectiveness and
efficiency of our proposed framework and algorithms.
PMID- 25133753
TI - Adaptive properties of human cementum and cementum dentin junction with age.
AB - OBJECTIVES: The objective of this study was to evaluate age related changes in
physical (structure/mechanical properties) and chemical (elemental/inorganic
mineral content) properties of cementum layers interfacing dentin. METHODS: Human
mandibular molars (N=43) were collected and sorted by age (younger=19-39,
middle=40-60, older=61-81 years). The structures of primary and secondary
cementum (PC, SC) types were evaluated using light and atomic force microscopy
(AFM) techniques. Chemical composition of cementum layers were characterized
through gravimetric analysis by estimating ash weight and concentrations of Ca,
Mn, and Zn trace elements in the analytes through inductively coupled plasma mass
spectroscopy. The hardness of PC and SC was determined using microindentation and
site-specific reduced elastic modulus properties were determined using
nanoindentation techniques. RESULTS: PC contained fibrous 1-3 um wide hygroscopic
radial PDL-inserts. SC illustrated PC-like structure adjacent to a multilayered
architecture composing of regions that contained mineral dominant lamellae. The
width of the cementum dentin junction (CDJ) decreased as measured from the
cementum enamel junction (CEJ) to the tooth apex (49-21 um), and significantly
decreased with age (44-23 um; p<0.05). The inorganic ratio defined as the ratio
of post-burn to pre-burn weight increased with age within primary cementum (PC)
and secondary cementum (SC). Cementum showed an increase in hardness with age (PC
(0.40-0.46 GPa), SC (0.37-0.43 GPa)), while dentin showed a decreasing trend
(coronal dentin (0.70-0.72 GPa); apical dentin (0.63-0.73 GPa)). SIGNIFICANCE:
The observed physicochemical changes are indicative of increased mineralization
of cementum and CDJ over time. Changes in tissue properties of teeth can alter
overall tooth biomechanics and in turn the entire bone-tooth complex including
the periodontal ligament. This study provides baseline information about the
changes in physicochemical properties of cementum with age, which can be
identified as adaptive in nature.
PMID- 25133754
TI - Parenting and the Family Check-Up: Changes in Observed Parent-Child Interaction
Following Early Childhood Intervention.
AB - Coercion theory posits a cyclical relationship between harsh and coercive parent
child interactions and problem behavior beginning in early childhood. As coercive
interactions have been theorized and found to facilitate the development and
growth of early conduct problems, early interventions often target parenting to
prevent or reduce early disruptive problem behavior. This study utilizes direct
observations of parent-child interactions from the Early Steps Multisite study (N
= 731; 369 boys) to examine the effect of the Family Check-Up, a family-centered
intervention program, on measures of parent-child positive engagement and
coercion from age 2 through 5, as well as on childhood problem behavior at age 5.
Results indicate that high levels of parent-child positive engagement were
associated with less parent-child coercion the following year, but dyadic
coercion was unrelated to future levels of positive engagement. In addition,
families assigned to the Family Check-Up showed increased levels of positive
engagement at ages 3 and 5, and the association between positive engagement at
age 3 and child problem behavior at age 5 was mediated by reductions in parent
child coercion at age 4. These findings provide longitudinal confirmation that
increasing positive engagement in parent-child interaction can reduce the
likelihood of coercive family dynamics in early childhood and growth in problem
behavior.
PMID- 25133756
TI - Restoration as mitigation: analysis of stream mitigation for coal mining impacts
in southern Appalachia.
AB - Compensatory mitigation is commonly used to replace aquatic natural resources
being lost or degraded but little is known about the success of stream
mitigation. This article presents a synthesis of information about 434 stream
mitigation projects from 117 permits for surface mining in Appalachia. Data from
annual monitoring reports indicate that the ratio of lengths of stream impacted
to lengths of stream mitigation projects were <1 for many projects, and most
mitigation was implemented on perennial streams while most impacts were to
ephemeral and intermittent streams. Regulatory requirements for assessing project
outcome were minimal; visual assessments were the most common and 97% of the
projects reported suboptimal or marginal habitat even after 5 years of
monitoring. Less than a third of the projects provided biotic or chemical data;
most of these were impaired with biotic indices below state standards and stream
conductivity exceeding federal water quality criteria. Levels of selenium known
to impair aquatic life were reported in 7 of the 11 projects that provided Se
data. Overall, the data show that mitigation efforts being implemented in
southern Appalachia for coal mining are not meeting the objectives of the Clean
Water Act to replace lost or degraded streams ecosystems and their functions.
PMID- 25133755
TI - Nutritional status in community-dwelling elderly in France in urban and rural
areas.
AB - Malnutrition is a frequent condition in elderly people, especially in nursing
homes and geriatric wards. Its frequency is less well known among elderly living
at home. The objective of this study was to describe the nutritional status
evaluated by the Mini Nutritional Assessment (MNA) of elderly community-dwellers
living in rural and urban areas in France and to investigate its associated
factors. METHODS: Subjects aged 65 years and over from the Approche
Multidisciplinaire Integree (AMI) cohort (692 subjects living in a rural area)
and the Three-City (3C) cohort (8,691 subjects living in three large urban zones)
were included. A proxy version of the MNA was reconstructed using available data
from the AMI cohort. Sensitivity and specificity were used to evaluate the
agreement between the proxy version and the standard version in AMI. The proxy
MNA was computed in both cohorts to evaluate the frequency of poor nutritional
status. Factors associated with this state were investigated in each cohort
separately. RESULTS: In the rural sample, 38.0% were females and the mean age was
75.5 years. In the urban sample, 60.3% were females and the mean age was 74.1
years. Among subjects in living in the rural sample, 7.4% were in poor
nutritional status while the proportion was 18.5% in the urban sample. Female
gender, older age, being widowed, a low educational level, low income, low body
mass index, being demented, having a depressive symptomatology, a loss of
autonomy and an intake of more than 3 drugs appeared to be independently
associated with poor nutritional status. CONCLUSION: Poor nutritional status was
commonly observed among elderly people living at home in both rural and urban
areas. The associated factors should be further considered for targeting
particularly vulnerable individuals.
PMID- 25133757
TI - Evaluating landscape options for corridor restoration between giant panda
reserves.
AB - The establishment of corridors can offset the negative effects of habitat
fragmentation by connecting isolated habitat patches. However, the practical
value of corridor planning is minimal if corridor identification is not based on
reliable quantitative information about species-environment relationships. An
example of this need for quantitative information is planning for giant panda
conservation. Although the species has been the focus of intense conservation
efforts for decades, most corridor projects remain hypothetical due to the lack
of reliable quantitative researches at an appropriate spatial scale. In this
paper, we evaluated a framework for giant panda forest corridor planning. We
linked our field survey data with satellite imagery, and conducted species
occupancy modelling to examine the habitat use of giant panda within the
potential corridor area. We then conducted least-cost and circuit models to
identify potential paths of dispersal across the landscape, and compared the
predicted cost under current conditions and alternative conservation management
options considered during corridor planning. We found that due to giant panda's
association with areas of low elevation and flat terrain, human infrastructures
in the same area have resulted in corridor fragmentation. We then identified
areas with high potential to function as movement corridors, and our analysis of
alternative conservation scenarios showed that both forest/bamboo restoration and
automobile tunnel construction would significantly improve the effectiveness of
corridor, while residence relocation would not significantly improve corridor
effectiveness in comparison with the current condition. The framework has general
value in any conservation activities that anticipate improving habitat
connectivity in human modified landscapes. Specifically, our study suggested
that, in this landscape, automobile tunnels are the best means to remove current
barriers to giant panda movements caused by anthropogenic interferences.
PMID- 25133758
TI - Microretroreflector-sedimentation immunoassays for pathogen detection.
AB - Point-of-care detection of pathogens is medically valuable but poses challenging
trade-offs between instrument complexity and clinical and analytical sensitivity.
Here we introduce a diagnostic platform utilizing lithographically fabricated
micron-scale forms of cubic retroreflectors, arguably one of the most optically
detectable human artifacts, as reporter labels for use in sensitive immunoassays.
We demonstrate the applicability of this novel optical label in a simple assay
format in which retroreflector cubes are first mixed with the sample. The cubes
are then allowed to settle onto an immuno-capture surface, followed by inversion
for gravity-driven removal of nonspecifically bound cubes. Cubes bridged to the
capture surface by the analyte are detected using inexpensive, low-numerical
aperture optics. For model bacterial and viral pathogens, sensitivity in 10%
human serum was found to be 10(4) bacterial cells/mL and 10(4) virus
particles/mL, consistent with clinical utility.
PMID- 25133759
TI - Association of poor subjective sleep quality with risk for death by suicide
during a 10-year period: a longitudinal, population-based study of late life.
AB - IMPORTANCE: Older adults have high rates of sleep disturbance, die by suicide at
disproportionately higher rates compared with other age groups, and tend to visit
their physician in the weeks preceding suicide death. To our knowledge, to date,
no study has examined disturbed sleep as an independent risk factor for late-life
suicide. OBJECTIVE: To examine the relative independent risk for suicide
associated with poor subjective sleep quality in a population-based study of
older adults during a 10-year observation period. DESIGN, SETTING, AND
PARTICIPANTS: A longitudinal case-control cohort study of late-life suicide among
a multisite, population-based community sample of older adults participating in
the Established Populations for Epidemiologic Studies of the Elderly. Of 14 456
community older adults sampled, 400 control subjects were matched (on age, sex,
and study site) to 20 suicide decedents. MAIN OUTCOMES AND MEASURES: Primary
measures included the Sleep Quality Index, the Center for Epidemiologic Studies
Depression Scale, and vital statistics. RESULTS: Hierarchical logistic
regressions revealed that poor sleep quality at baseline was significantly
associated with increased risk for suicide (odds ratio [OR], 1.39; 95% CI, 1.14
1.69; P < .001) by 10 follow-up years. In addition, 2 sleep items were
individually associated with elevated risk for suicide at 10-year follow-up:
difficulty falling asleep (OR, 2.24; 95% CI, 1.27-3.93; P < .01) and
nonrestorative sleep (OR, 2.17; 95% CI, 1.28-3.67; P < .01). Controlling for
depressive symptoms, baseline self-reported sleep quality was associated with
increased risk for death by suicide (OR, 1.30; 95% CI, 1.04-1.63; P < .05).
CONCLUSIONS AND RELEVANCE: Our results indicate that poor subjective sleep
quality is associated with increased risk for death by suicide 10 years later,
even after adjustment for depressive symptoms. Disturbed sleep appears to confer
considerable risk, independent of depressed mood, for the most severe suicidal
behaviors and may warrant inclusion in suicide risk assessment frameworks to
enhance detection of risk and intervention opportunity in late life.
PMID- 25133761
TI - Multiple DNA architectures with the participation of inorganic metal ions.
AB - Here we develop a synthetic protocol for assembling DNA with participating metal
ions into multiple shapes. DNA molecules first form coordination complexes with
metal ions and these coordination complexes become nucleation sites for primary
crystals of metal inorganic salt, and then elementary units of space-filling
architectures based on specific geometry form, and finally elementary units
assemble into variously larger multiple architectures according to different
spatial configurations. We anticipate that our strategy for self-assembling
various custom architectures is applicable to most biomolecules possessing donor
atoms that can form coordination complexes with metal ions. These multiple
architectures provide a general platform for the engineering and assembly of
advanced materials possessing features on the micrometer scale and having novel
activity.
PMID- 25133762
TI - Response to comment on "Mercury biomagnification through food webs is affected by
physical and chemical characteristics of lakes".
PMID- 25133760
TI - Left and right lung asynchrony as a physiological indicator for unilateral
bronchial obstruction in interventional bronchoscopy.
AB - BACKGROUND: In patients with bronchial obstruction, pulmonary function tests may
not change significantly after intervention. The airflow asynchrony in both lungs
due to unilateral bronchial obstruction may be applicable as a physiological
indicator. The airflow asynchrony is reflected by the difference in the left and
right lung sound development at tidal breathing. OBJECTIVES: To investigate the
usefulness of left and right lung asynchrony due to unilateral bronchial
obstruction as a physiological indicator for interventional bronchoscopy.
METHODS: Fifty cases with central airway obstruction were classified into three
groups: tracheal, bronchial and extensive obstruction. The gap index was defined
as the absolute value of the average of gaps between the left and right lung
sound intensity peaks for a 12-second duration. RESULTS: Before interventional
bronchoscopy, the gap index was significantly higher in the bronchial (p<0.05)
and extensive obstruction groups (p<0.05) than in the tracheal group. The gap
index in cases with unilateral bronchial obstruction of at least 80% (0.18+/-0.04
seconds) was significantly higher than in cases with less than 80% obstruction
(0.02+/-0.01 seconds, p<0.05). After intervention for bronchial obstruction, the
dyspnea scale (p<0.001) and gap index significantly improved (p<0.05), although
no significant improvements were found in spirometric assessments. The responder
rates for dyspnea were 79.3% for gap indexes over 0.06 seconds and 55.6% for gap
indexes of 0.06 seconds or under. CONCLUSIONS: Assessment of left and right lung
asynchrony in central airway obstruction with bronchial involvement may provide
useful physiological information for interventional bronchoscopy.
PMID- 25133763
TI - Creating an effective campaign for change: strategies for teaching value.
PMID- 25133764
TI - Single molecule DNA intercalation in continuous homogenous elongational flow.
AB - Sequence-nonspecific staining of DNA with intercalating fluorophores is required
for fluorescence-based length estimation of elongated DNA in optical mapping
techniques. However, the observed length of a DNA molecule is affected by the
relative concentrations of DNA and dye. In some applications, predetermination of
DNA concentration may not be possible. Here we present a microfluidic approach in
which individual DNA molecules are entrained by converging laminar sheath flows
containing the intercalating dye PO-PRO-1. This provides uniform staining
regardless of DNA concentration, and uniform elastic stretching of DNA in
continuous elongational flow. On-chip intercalation provides a unique process for
concentration-independent staining of long DNA fragments for the optical mapping
method Genome Sequence Scanning (GSS), and normalizes intramolecular elasticity
across a broad range of molecule lengths. These advances permit accurate mapping
of observed molecules to sequence derived templates, thus improving detection of
complex bacterial mixtures using GSS.
PMID- 25133765
TI - Issues in online patient self-reporting of health status.
AB - Patient self-reporting of symptoms and quality of life following surgical
interventions is generally delivered in the form of paper-based questionnaires to
be completed in the outpatient clinic or at home. A commonly used tool for
patient self-reporting of quality of life is the EQ5D health status questionnaire
which, while limited in scope, has general applicability across a range of health
interventions. In this article we examine the issues relating to online patient
self-reporting using this questionnaire and the wider implications for the online
reporting of health status.
PMID- 25133766
TI - Rounds reports: Early experiences of using printed summaries of electronic
medical records in a large teaching medical hospital.
AB - This article describes the rationale, processes, technology, and results of
creating of a paper-based rounds report that is now used by our entire
institution for efficient inpatient work rounds and checkout rounds that are
routinely done in virtually every hospital, both academic and private, in the US.
The results of a survey of clinicians suggests that printed rounds reports have
markedly improved rounding efficiency, saved substantial amounts of physician
time, standardized checkout processes, and improved patient safety.
PMID- 25133767
TI - What you see is not what you get in the PDF document format.
AB - The sharing and storage of scientific knowledge, information and data are today
mainly in digitized form, which will become the predominant means of
communicating scientific work in the future. One of the best-established formats
is the open standard of PDF (Portable Document Format), which is renowned for its
flexibility and stability. In this article, we expose a major flaw in the format
with respect to the security of confidential information, such that even
organizations responsible for safeguarding and setting the standards for data
management were unintentionally revealing confidential patient data. By
collecting and analysing a random sample of files from a health informatics
organization, we demonstrate the extent of the problem and determine its cause by
code analysis of an example. In conclusion, we suggest the development of a
knowledge-sharing format that does not demand expert skills for safe usage:
WYSIWYS (What You See Is What You Store).
PMID- 25133768
TI - Robotic agents for supporting community-dwelling elderly people with memory
complaints: Perceived needs and preferences.
AB - Researchers in robotics have been increasingly focusing on robots as a means of
supporting older people with cognitive impairment at home. The aim of this study
is to explore the elderly's needs and preferences towards having an assistive
robot in the home. In order to ensure the appropriateness of this technology, 30
subjects aged 60 and older with memory complaints were recruited from the Memory
Clinic of the Broca Hospital. We conducted an interview-administered
questionnaire that included questions about their needs and preferences
concerning robot functions and modes of action. The subjects reported a desire to
retain their capacity to manage their daily activities, to maintain good health
and to stimulate their memory. Regarding robot functions, the cognitive
stimulation programme earned the highest proportion of positive responses,
followed by the safeguarding functions, fall detection and the automatic help
call.
PMID- 25133769
TI - Matching AIDS and tuberculosis registry data to identify AIDS/tuberculosis
comorbidity cases in California.
AB - The purpose of this study was to evaluate the sensitivity and positive predictive
value (PPV) of a registry data linkage procedure used in the California AIDS and
Tuberculosis (TB) Registry Data Linkage Study to identify AIDS/TB comorbidity
cases in California. The California AIDS registry data from 1981 to 2006 were
linked to the California TB registry data from 1996 to 2006 using LinkPlus, a
probabilistic record linkage program developed by the Centers for Disease Control
and Prevention, and matched results were manually reviewed to determine true or
false matches. We estimated the sensitivity of this procedure to range from 98.0
per cent (95% confidence interval, CI: 97.3%, 98.7%) to 98.8 per cent (95% CI:
98.1%, 99.2%), and the PPV to be 100 per cent (95% CI: 96.8%, 100.0%). Our study
demonstrated the feasibility of using this linkage procedure to match AIDS and TB
registry data with a very high degree of accuracy.
PMID- 25133770
TI - Electronic patient records in action: Transforming information into
professionally relevant knowledge.
AB - The implementation of generic models for organizing information in complex
institutions like those in healthcare creates a gap between standardization and
the need for locally relevant knowledge. The present study addresses how this gap
can be bridged by focusing on the practical work of healthcare staff in
transforming information in EPRs into knowledge that is useful for everyday work.
Video recording of shift handovers on a rehabilitation ward serves as the
empirical case. The results show how extensive selections and reorganizations of
information in EPRs are carried out in order to transform information into
professionally relevant accounts. We argue that knowledge about the institutional
obligations and professional ways of construing information are fundamental for
these transitions. The findings point to the need to consider the role of
professional knowledge inherent in unpacking information in efforts to develop
information systems intended to bridge between institutional and professional
boundaries in healthcare.
PMID- 25133771
TI - Personal health records: Consumer attitudes toward privacy and security of their
personal health information.
AB - Personal health record (PHR) systems are a subject of intense interest in the
move to improve healthcare accessibility and quality. Although a number of
vendors continue to put forward PHR systems, user-centered design research has
lagged, and it has not been clear what features are important to prospective PHR
users. Here, we report on a user-centered design study that combines qualitative
and quantitative approaches to investigate several dimensions relevant to PHR
design, and to look at the effect of health status on user needs. The results
indicate that health status, especially disability and chronic illness, is
relevant to PHR design. Further, the results provide empirical evidence about the
role of privacy and security in users' attitudes toward PHR use. The exact nature
of these attitudes differs from widely held perceptions about consumer values in
healthcare information management.
PMID- 25133772
TI - Maximizing acceptability and usefulness of an automated telephone intervention:
Lessons from a developmental mixed-methods approach.
AB - The objective was to describe the utility of mixed methods to inform the
development of an automated telephone intervention to improve patients'
compliance with asthma medication. As part of intervention development for a
larger trial, we conducted 15 focus groups (n = 53) to design and develop calls,
and to identify factors influencing intervention acceptability and usefulness. We
piloted four call types and interviewed 64 participants to further improve call
content and receptivity to the intervention. Feedback led to several changes to
the intervention scripts and eventual calls, and an initial pilot led us to drop
one of the calls. During the pilot, we reached 43 percent of target participants;
74 percent of those stayed on the call until it ended. This process provided key
insights about automated calls, and may have broader applicability for the
development of automated interventions designed to help patients manage a variety
of chronic conditions.
PMID- 25133774
TI - Genome-wide characterization of insertion and deletion variation in chicken using
next generation sequencing.
AB - Insertion and deletion (INDEL) is one of the main events contributing to genetic
and phenotypic diversity, which receives less attention than SNP and large
structural variation. To gain a better knowledge of INDEL variation in chicken
genome, we applied next generation sequencing on 12 diverse chicken breeds at an
average effective depth of 8.6. Over 1.3 million non-redundant short INDELs (1-49
bp) were obtained, the vast majority (92.48%) of which were novel. Follow-up
validation assays confirmed that most (88.00%) of the randomly selected INDELs
represent true variations. The majority (95.76%) of INDELs were less than 10 bp.
Both the detected number and affected bases were larger for deletions than
insertions. In total, INDELs covered 3.8 Mbp, corresponding to 0.36% of the
chicken genome. The average genomic INDEL density was estimated as 0.49 per kb.
INDELs were ubiquitous and distributed in a non-uniform fashion across
chromosomes, with lower INDEL density in micro-chromosomes than in others, and
some functional regions like exons and UTRs were prone to less INDELs than
introns and intergenic regions. Nearly 620,253 INDELs fell in genic regions,
1,765 (0.28%) of which located in exons, spanning 1,358 (7.56%) unique Ensembl
genes. Many of them are associated with economically important traits and some
are the homologues of human disease-related genes. We demonstrate that sequencing
multiple individuals at a medium depth offers a promising way for reliable
identification of INDELs. The coding INDELs are valuable candidates for further
elucidation of the association between genotypes and phenotypes. The chicken
INDELs revealed by our study can be useful for future studies, including
development of INDEL markers, construction of high density linkage map, INDEL
arrays design, and hopefully, molecular breeding programs in chicken.
PMID- 25133775
TI - Sirt1 and Sirt6 mediate beneficial effects of rosiglitazone on hepatic lipid
accumulation.
AB - BACKGROUND: Sirtuin (Sirt), a sensor of the cell metabolic state, regulates
glucose and lipid metabolism. The aim of this study was to address whether
rosiglitazone (RGZ) alters hepatic Sirt1 and whether Sirt1 and/or Sirt6 have a
regulatory role in the protective effects of RGZ on hepatocyte steatosis.
METHODS: To investigate the effect of RGZ on hepatic Sirt1, rats were
administered with RGZ for 6 weeks. The involvement of Sirt1/6 in the RGZ-mediated
effect against hepatic steatosis was evaluated by single or double knockdown of
Sirt1 and Sirt6 in a hepatocyte steatosis model. RESULTS: RGZ in vivo increased
Sirt1 expression and its activity in rat livers. In a hepatocyte steatosis model,
RGZ significantly reduced lipid accumulation and activated the Sirt1/6-LKB1-AMPK
pathway. Sirt1 knockdown abolished the effects of RGZ with regard to hepatocyte
fat accumulation and the Sirt1/6-LKB1-AMPK pathway, suggesting that Sirt1 is a
key regulator of RGZ-mediated metabolic processes. Sirt6 knockdown inhibited the
protective effects of RGZ to a lesser extent than Sirt1, and double knockdown of
Sirt1/6 showed no synergistic effects. CONCLUSION: Our results demonstrate that
Sirt1/6 are involved in the RGZ-mediated effects on hepatocyte steatosis, and the
regulatory effects of Sirt1 and Sirt6 are not synergistic but compensatory for
improving hepatocyte steatosis.
PMID- 25133776
TI - Silver-catalyzed domino hydroarylation/cycloisomerization reactions of ortho
alkynylbenzaldehydes: an entry to functionalized isochromene derivatives.
AB - A Ag-catalyzed versatile and efficient access to 1H,1-arylisochromenes is
reported. Starting from ortho-alkynylbenzaldehydes bearing various substitution
patterns on the benzaldehyde and alkynyl units, the use of silver triflate (10
mol %) allowed a domino hydroarylation/cycloisomerization reaction process,
leading to aryl-functionalized 1H-isochromene (>10 compounds, 80-98% yields).
Notably, the reaction conditions were also compatible with benzaldehydes bearing
an aliphatic-substituted alkynyl moiety with modest to good yields (34-88%, 10
compounds).
PMID- 25133778
TI - Adaptive evolution and divergence of SERPINB3: a young duplicate in great Apes.
AB - A series of duplication events led to an expansion of clade B Serine Protease
Inhibitors (SERPIN), currently displaying a large repertoire of functions in
vertebrates. Accordingly, the recent duplicates SERPINB3 and B4 located in human
18q21.3 SERPIN cluster control the activity of different cysteine and serine
proteases, respectively. Here, we aim to assess SERPINB3 and B4 coevolution with
their target proteases in order to understand the evolutionary forces shaping the
accelerated divergence of these duplicates. Phylogenetic analysis of primate
sequences placed the duplication event in a Hominoidae ancestor (~30 Mya) and the
emergence of SERPINB3 in Homininae (~9 Mya). We detected evidence of strong
positive selection throughout SERPINB4/B3 primate tree and target proteases,
cathepsin L2 (CTSL2) and G (CTSG) and chymase (CMA1). Specifically, in the
Homininae clade a perfect match was observed between the adaptive evolution of
SERPINB3 and cathepsin S (CTSS) and most of sites under positive selection were
located at the inhibitor/protease interface. Altogether our results seem to
favour a coevolution hypothesis for SERPINB3, CTSS and CTSL2 and for SERPINB4 and
CTSG and CMA1. A scenario of an accelerated evolution driven by host-pathogen
interactions is also possible since SERPINB3/B4 are potent inhibitors of
exogenous proteases, released by infectious agents. Finally, similar patterns of
expression and the sharing of many regulatory motifs suggest neofunctionalization
as the best fitted model of the functional divergence of SERPINB3 and B4
duplicates.
PMID- 25133777
TI - HPLC-MS/MS analyses show that the near-Starchless aps1 and pgm leaves accumulate
wild type levels of ADPglucose: further evidence for the occurrence of important
ADPglucose biosynthetic pathway(s) alternative to the pPGI-pPGM-AGP pathway.
AB - In leaves, it is widely assumed that starch is the end-product of a metabolic
pathway exclusively taking place in the chloroplast that (a) involves plastidic
phosphoglucomutase (pPGM), ADPglucose (ADPG) pyrophosphorylase (AGP) and starch
synthase (SS), and (b) is linked to the Calvin-Benson cycle by means of the
plastidic phosphoglucose isomerase (pPGI). This view also implies that AGP is the
sole enzyme producing the starch precursor molecule, ADPG. However, mounting
evidence has been compiled pointing to the occurrence of important sources, other
than the pPGI-pPGM-AGP pathway, of ADPG. To further explore this possibility, in
this work two independent laboratories have carried out HPLC-MS/MS analyses of
ADPG content in leaves of the near-starchless pgm and aps1 mutants impaired in
pPGM and AGP, respectively, and in leaves of double aps1/pgm mutants grown under
two different culture conditions. We also measured the ADPG content in wild type
(WT) and aps1 leaves expressing in the plastid two different ADPG cleaving
enzymes, and in aps1 leaves expressing in the plastid GlgC, a bacterial AGP.
Furthermore, we measured the ADPG content in ss3/ss4/aps1 mutants impaired in
starch granule initiation and chloroplastic ADPG synthesis. We found that,
irrespective of their starch contents, pgm and aps1 leaves, WT and aps1 leaves
expressing in the plastid ADPG cleaving enzymes, and aps1 leaves expressing in
the plastid GlgC accumulate WT ADPG content. In clear contrast, ss3/ss4/aps1
leaves accumulated ca. 300 fold-more ADPG than WT leaves. The overall data showed
that, in Arabidopsis leaves, (a) there are important ADPG biosynthetic pathways,
other than the pPGI-pPGM-AGP pathway, (b) pPGM and AGP are not major determinants
of intracellular ADPG content, and (c) the contribution of the chloroplastic ADPG
pool to the total ADPG pool is low.
PMID- 25133779
TI - Changes in gastric and lung microflora with acid suppression: acid suppression
and bacterial growth.
AB - IMPORTANCE: The use of acid suppression has been associated with an increased
risk of upper and lower respiratory tract infections in the outpatient setting
but the mechanism behind this increased risk is unknown. We hypothesize that this
infection risk results from gastric bacterial overgrowth with subsequent seeding
of the lungs. OBJECTIVES: To determine if acid-suppression use results in gastric
bacterial overgrowth, if there are changes in lung microflora associated with the
use of acid suppression, and if changes in lung microflora are related to full
column nonacid gastroesophageal reflux. DESIGN, SETTING, AND PARTICIPANTS: A 5
year prospective cohort study at a tertiary care center where children ages 1 to
18 years were undergoing bronchoscopy and endoscopy for the evaluation of chronic
cough. Acid-suppression use was assessed through questionnaires with confirmation
using an electronic medical record review. MAIN OUTCOMES AND MEASURES: Our
primary outcome was to compare differences in concentration and prevalence of
gastric and lung bacteria between patients who were and were not receiving acid
suppression therapy. We compared medians using the Wilcoxon signed rank test and
determined prevalence ratios using asymptotic standard errors and 95% confidence
intervals. We determined correlations between continuous variables using Pearson
correlation coefficients and compared categorical variables using the Fisher
exact test. RESULTS: Forty-six percent of patients taking acid-suppression
medication had gastric bacterial growth compared with 18% of untreated patients
(P = .003). Staphylococcus (prevalence ratio, 12.75 [95% CI, 1.72-94.36]),
Streptococcus (prevalence ratio, 6.91 [95% CI, 1.64-29.02]), Veillonella
(prevalence ratio, 9.56 [95% CI, 1.26-72.67]), Dermabacter (prevalence ratio,
4.78 [95% CI, 1.09-21.02]), and Rothia (prevalence ratio, 6.38 [95% CI, 1.50
27.02]) were found more commonly in the gastric fluid of treated patients. The
median bacterial concentration was higher in treated patients than in untreated
patients (P = .001). There was no difference in the prevalence (P > .23) of
different bacterial genera or the median concentration of total bacteria (P =
.85) in the lungs between treated and untreated patients. There were significant
positive correlations between proximal nonacid reflux burden and lung
concentrations of Bacillus (r = 0.47, P = .005), Dermabacter (r = 0.37, P =
.008), Lactobacillus (r = 0.45, P = .001), Peptostreptococcus (r = 0.37, P =
.008), and Capnocytophagia (r = 0.37, P = .008). CONCLUSIONS AND RELEVANCE: Acid
suppression use results in gastric bacterial overgrowth of genera including
Staphylococcus and Streptococcus. Full-column nonacid reflux is associated with
greater concentrations of bacteria in the lung. Additional studies are needed to
determine if acid suppression-related microflora changes predict clinical
infection risk; these results suggest that acid suppression use may need to be
limited in patients at risk for infections.
PMID- 25133781
TI - Programmable resistive-switch nanowire transistor logic circuits.
AB - Programmable logic arrays (PLA) constitute a promising architecture for
developing increasingly complex and functional circuits through nanocomputers
from nanoscale building blocks. Here we report a novel one-dimensional PLA
element that incorporates resistive switch gate structures on a semiconductor
nanowire and show that multiple elements can be integrated to realize functional
PLAs. In our PLA element, the gate coupling to the nanowire transistor can be
modulated by the memory state of the resistive switch to yield programmable
active (transistor) or inactive (resistor) states within a well-defined logic
window. Multiple PLA nanowire elements were integrated and programmed to yield a
working 2-to-4 demultiplexer with long-term retention. The well-defined,
controllable logic window and long-term retention of our new one-dimensional PLA
element provide a promising route for building increasingly complex circuits with
nanoscale building blocks.
PMID- 25133780
TI - Rearing in seawater mesocosms improves the spawning performance of growth hormone
transgenic and wild-type coho salmon.
AB - Growth hormone (GH) transgenes can significantly accelerate growth rates in fish
and cause associated alterations to their physiology and behaviour. Concern
exists regarding potential environmental risks of GH transgenic fish, should they
enter natural ecosystems. In particular, whether they can reproduce and generate
viable offspring under natural conditions is poorly understood. In previous
studies, GH transgenic salmon grown under contained culture conditions had lower
spawning behaviour and reproductive success relative to wild-type fish reared in
nature. However, wild-type salmon cultured in equal conditions also had limited
reproductive success. As such, whether decreased reproductive success of GH
transgenic salmon is due to the action of the transgene or to secondary effects
of culture (or a combination) has not been fully ascertained. Hence, salmon were
reared in large (350,000 L), semi-natural, seawater tanks (termed mesocosms)
designed to minimize effects of standard laboratory culture conditions, and the
reproductive success of wild-type and GH transgenic coho salmon from mesocosms
were compared with that of wild-type fish from nature. Mesocosm rearing partially
restored spawning behaviour and success of wild-type fish relative to culture
rearing, but remained lower overall than those reared in nature. GH transgenic
salmon reared in the mesocosm had similar spawning behaviour and success as wild
type fish reared in the mesocosm when in full competition and without
competition, but had lower success in male-only competition experiments. There
was evidence of genotype*environmental interactions on spawning success, so that
spawning success of transgenic fish, should they escape to natural systems in
early life, cannot be predicted with low uncertainty. Under the present
conditions, we found no evidence to support enhanced mating capabilities of GH
transgenic coho salmon compared to wild-type salmon. However, it is clear that GH
transgenic salmon are capable of successful spawning, and can reproduce with wild
type fish from natural systems.
PMID- 25133782
TI - Stimuli-sensitive breathing of Cucurbit[7]uril cavity: monitoring through the
environment responsive fluorescence of 1'-hydroxy-2'-acetonaphthone (HAN).
AB - In this work, we have focused on the supramolecular interactions of a water
soluble host Cucurbit[7]uril (CB[7]) with an excited state intramolecular proton
transfer (ESIPT) probe 1'-hydroxy-2'-acetonaphthone (HAN) through steady-state
and time-resolved fluorescence measurements. In water HAN is almost
nonfluorescent in nature with a very low fluorescence quantum yield (Phi =
0.009). With gradual addition of CB[7] absorption maximum of HAN is red-shifted
(292 cm(-1)) and hence confirming the formation of an inclusion complex in the
ground state between HAN and CB[7]. Due to this complexation CB[7] offers a
hydrophobic microenvironment to the HAN which is completely different from that
of homogeneous water. Upon encapsulation into the nanocavity of CB[7], HAN
exhibits a 20-fold increase in fluorescence intensity along with a 36 nm (1618
cm(-1)) hypsochromic shift in emission maxima. This hypsochromic shift is an
indication about the modulation of excited state photophysical behavior of HAN
due to the formation of HAN-CB[7] inclusion complex. Moreover, huge partition
coefficient of HAN from water to CB[7] along with a~ 12-fold increase in
fluorescence lifetime confirm the favorable interaction between HAN and CB[7]. We
have also observed the stimuli-sensitive (temperature and cationic stimuli)
breathing of CB[7] cavity i.e., in the presence of different additives the
portals of CB[7] open up to release HAN in water and take up the additives. Time
resolved anisotropy measurements further indicate about the probable location of
HAN inside the CB[7]. The observation of a 1.7 ns component in the presence of
CB[7] signifies the highly restricted rotational motion of HAN inside the cavity
of CB[7] corroborates our finding.
PMID- 25133783
TI - Clinical exome sequencing: the new standard in genetic diagnosis.
PMID- 25133784
TI - Diffusion and seed shape: intertwined parameters in the synthesis of branched
metal nanostructures.
AB - Branched nanocrystals display interesting optical and catalytic properties on
account of their high surface areas and tips with small radii of curvatures.
However, many synthetic routes toward branched nanocrystals result in
inhomogeneous samples on account of asymmetric branching. Seed-mediated
coreduction is a recently developed route to symmetrically branched nanocrystals
where the symmetry of the seeds is transferred to the final stellated
morphologies. Here, general guidelines to stellated nanocrystals are outlined by
surveying coreduction of Au and Pd precursors in the presence of a variety of
shape-controlled Au seeds to achieve Au/Pd nanostructures. Single-crystalline,
twinned, and anisotropic seeds were analyzed to expand the classes of stellated
nanostructures synthetically accessible. Significantly, single-crystalline Au
seeds adopt {100}-terminated intermediates prior to branching, regardless of
initial seed shape. We compared these results with those obtained with shape
controlled Pd seeds, and seed composition was identified as an important
synthetic parameter, with Pd seeds being more resistant to shape changes during
overgrowth. This difference is attributed to the greater diffusion rate of Au
atoms on Au seeds compared to Au atoms on Pd seeds. These results provide
guidelines for the seeded synthesis of symmetrically branched nanocrystals and
architecturally defined bimetallic nanostructures in general.
PMID- 25133785
TI - Characteristics and survival to discharge of patients with STEMI between a PPCI
capable hospital and a non-PPCI hospital: a prospective observational study.
AB - INTRODUCTION: Primary percutaneous coronary intervention (PPCI) is a key
therapeutic method in the treatment of ST-elevation myocardial infarction
(STEMI). We studied the characteristics and survival to discharge in STEMI
patients who presented in a PPCI-capable hospital and a non-PPCI hospital.
PATIENTS AND METHODS: This prospective observational study included 240
consecutive patients. One basic questionnaire was distributed along with an
explanatory letter to the participants, who were followed until discharge from
the hospital or death. RESULTS: Of the 240 patients, 234 (97.5%) survived to
hospital discharge. Only 6 (5%) patients who were initially presented to a non
PPCI hospital died after inter-facility transfer. Also, 36 (92.3%) of the 39
patients with an intervening time of over 90 min were admitted initially in a non
PPCI hospital. Although there was a statistically significant correlation between
the type of the hospital and the delay from the onset of symptoms to PPCI
(P=0.001), such correlation was not found between the delay PPCI and the outcome
of the patients (P>0.05). CONCLUSION: Patients with STEMI may be transferred to a
non-PPCI hospital due to the lack of prehospital triage. However, prompt inter
facility transfer results in good outcome.
PMID- 25133786
TI - Potential determinants of drink driving in young adults.
AB - OBJECTIVE: The main purposes of this study were to examine the usefulness of the
variables of the theory of planned behavior (viz. attitudes, social norms, and
self-efficacy) and to explore the relationship between optimism bias and drink
driving in young adults. In addition, we explored gender differences in drink
driving with provision for the effect of variables such as driving frequency and
alcohol consumption. METHODS: Data were collected via a questionnaire
administered to 274 drivers (59.9% females) aged 18-30 years (24.36 +/- 2.96).
RESULTS: The results obtained with provision for driving frequency revealed
substantial differences in driving behaviors between genders. Thus, males were
more prone to drink driving, perceived less disapproval by their significant
others (parents and peers), and felt less able to avoid drinking-and-driving
situations. In addition, they self-reported more frequent alcohol consumption and
driving under the influence. The results also confirm the significance of peers'
subjective norms and attitudes to drink driving in males. Overconfidence in their
own driving skills for driving drunk and perceived behavioral control were found
to be significant predictors for drink driving in females. Optimism bias also
played a slightly significant role in predicting drink driving but only in
females. CONCLUSIONS: The important practical implications of these results with
a view to designing effective interventions to prevent the risks associated with
drink driving in the young population are discussed. Interventions should focus
on young people's perceptions of group norms and promoting cautionary driving
choices and alternatives to drink driving.
PMID- 25133789
TI - Influence of metal of the applicator on the dose distribution during
brachytherapy.
AB - This study explores how the metal materials of the applicator influence the dose
distribution when performing brachytherapy for cervical cancer. A pinpoint
ionization chamber, Monte Carlo code MCNPX, and treatment planning system are
used to evaluate the dose distribution for a single Ir-192 source positioned in
the tandem and ovoid. For dose distribution in water with the presence of the
tandem, differences among measurement, MCNPX calculation and treatment planning
system results are <5%. For dose distribution in water with the presence of the
ovoid, the MCNPX result agrees with the measurement. But the doses calculated
from treatment planning system are overestimated by up to a factor of 4. This is
due to the shielding effect of the metal materials in the applicator not being
considered in the treatment planning system. This result suggests that the
treatment planning system should take into account corrections for the metal
materials of the applicator in order to improve the accuracy of the radiation
dose delivered.
PMID- 25133787
TI - Development of a nuclear transformation system for Oleaginous Green Alga
Lobosphaera (Parietochloris) incisa and genetic complementation of a mutant
strain, deficient in arachidonic acid biosynthesis.
AB - Microalgae are considered a promising source for various high value products,
such as carotenoids, omega-3 and omega-6 polyunsaturated fatty acids (PUFA). The
unicellular green alga Lobosphaera (Parietochloris) incisa is an outstanding
candidate for the efficient phototrophic production of arachidonic acid (AA), an
essential omega-6 PUFA for infant brain development and a widely used ingredient
in the baby formula industry. Although phototrophic production of such algal
products has not yet been established, estimated costs are considered to be 2-5
times higher than competing heterotrophic production costs. This alga accumulates
unprecedented amounts of AA within triacylglycerols and the molecular pathway of
AA biosynthesis in L. incisa has been previously elucidated. Thus, progress in
transformation and metabolic engineering of this high value alga could be
exploited for increasing the efficient production of AA at competitive prices. We
describe here the first successful transformation of L. incisa using the ble gene
as a selection marker, under the control of the endogenous RBCS promoter.
Furthermore, we have succeeded in the functional complementation of the L. incisa
mutant strain P127, containing a mutated, inactive version of the delta-5
(Delta5) fatty acid desaturase gene. A copy of the functional Delta5 desaturase
gene, linked to the ble selection marker, was transformed into the P127 mutant.
The resulting transformants selected for zeocine resistant, had AA biosynthesis
partially restored, indicating the functional complementation of the mutant
strain with the wild-type gene. The results of this study present a platform for
the successful genetic engineering of L. incisa and its long-chain PUFA
metabolism.
PMID- 25133790
TI - Exposure to anticholinergic and sedative drugs, risk of falls, and mortality: an
elderly inpatient, multicenter cohort.
AB - This study aimed to assess whether exposure to anticholinergic and sedative
medications and its evolution was associated with increased risk of in-hospital
falls and all-cause mortality. Furthermore, results were compared with 2
definitions of drug burden index (DBI) against the outcomes.This observational,
multicentric, and longitudinal study was conducted among patients aged 65 years
or older, in 3 geriatric hospitals, in Francheville, Lyon, and Villeurbanne,
France (duration of follow-up, 11.6 months). The exposure to anticholinergic and
sedative medications was quantified using a DBI, at admission and at the end of
observation for 337 patients. The evolution of exposure was the absolute
difference between the index at admission and at the end of observation. The
outcomes were in-hospital falls and all-cause mortality.Overall, 5.9% of patients
experienced a fall. The risk of fall was nearly 3-fold in patients whose DBI
increased during hospital stay compared to those with stable or decreased DBI
(hazard ratio, 2.9 [1.14-7.12]; P = 0.03), after adjustment for comorbidities.The
overall proportion of mortality was 6.5%. The evolution of DBI during hospital
stay was not related to the risk of mortality (hazard ratio, 1.9 [0.8-4.4]; P =
0.14). Results were similar with the 2 definitions of DBI.Increased exposure to
anticholinergic and sedative medications during hospital stay is associated with
a higher risk of in-hospital falls but not with mortality. The DBI could be
implemented in hospital, to guide prescription and reduce anticholinergic and
sedative drug exposure.
PMID- 25133791
TI - Lactulose-associated lithium toxicity: a case series.
AB - BACKGROUND: Lactulose is commonly used for constipation and hepatic
encephalopathy. Its adverse effects of dehydration and serum electrolyte
imbalances are widely known. OBJECTIVE: This study aimed to describe a case
series of 3 patients receiving lactulose who developed lithium toxicity. METHODS:
The authors described a case series of 3 patients admitted to a large county
psychiatric hospital who developed lithium toxicity while taking lactulose for
constipation or hyperammonemia. RESULTS: In all 3 cases of lithium toxicity, the
patients were prescribed with lithium for acute mania and lactulose for
constipation or hyperammonemia. One case required the patient to be transferred
to a local emergency department for further treatment. CONCLUSIONS: This case
series shows the interaction between lithium and lactulose. It is postulated that
lactulose's effects of volume depletion can lead to poor renal excretion of
lithium.
PMID- 25133792
TI - Influence of acoustic stimulation on the circadian and ultradian rhythm of
premature infants.
AB - The aim of the present study was to evaluate the development of the circadian
rhythm of the salivary cortisol in premature infants and its correlation with the
onset of the sleep-activity behavior pattern during the first 3 weeks of life
under controlled light:dark conditions. Furthermore, we investigated the
influence of acoustic stimulation by audiotaped lullabies or the maternal voice
on the cortisol values and long-term sleep-activity patterns. The study was a
block-randomized, prospective clinical trial with a study population of 62
preterm neonates (30<37 gestational age). We compared two study groups who
listened either to music or to the maternal voice (music: N=20; maternal voice:
N=20) with a matched control group (N=22). The acoustic stimulation took place
every evening between 20:00 and 21:00 h for 30 min over a period of 2 weeks. The
cortisol values and activity-rest behavior of the neonates were determined during
the first 3 weeks of life on the 1st, 7th and 14th day. Actigraphic monitoring
was used to record the activity pattern continuously over 24 h and a validated
algorithm for neonates was used to estimate sleep and wakefulness. The saliva
samples were obtained 10 min before and 10 min after the acoustic interventions
for the study groups. Additionally, saliva samples were obtained from the control
group seven times over a 24-h period (20:00, 21:00, 01:00, 05:00, 08:00, 13:00
and 17:00 h). The cortisol data were analyzed by fast Fourier transformation to
assess periodic characteristics and frequencies. Hierarchical linear modeling was
further performed for the statistical analysis. RESULTS: The cortisol rhythm
analysis indicated a circadian rhythm pattern for only one premature infant, all
others of the neonates showed no circadian or ultradian rhythm in cortisol.
Cortisol level of the premature neonates was significantly higher during the
first day of the study period at night-time (median: 17.1 nmol/L, IQR=9.7-24.4
nmol/L) than on days 7 (median: 9.6 nmol/L, IQR=4.7-14.6 nmol/L; Tukey-HSD,
z=4.12, p<0.001) and 14 (IQR=5.8-13.7 nmol/L; Tukey-HSD, z=2.89, p<0.05). No
significant effect of acoustic stimulation was observed on the cortisol
concentration and sleep-wake behavior. The activity-sleep rhythm of preterm
neonates was dominated by ultradian rhythm patterns with a prominent period
length of 4 h (30.5%). Activity frequencies of neonates were also significantly
higher overnight on the first study day (mean: 329+/-185.1 U) than of night seven
(mean: 260.2+/-132.4 U; Tukey-HSD, z=2.50, p<0.05). Quiet-activity patterns
increased, whereas high-activity patterns decreased during the observation
period. Average sleep time increased significantly during the study time from day
1 to day 7 (Tukey-HSD, z=2.51, p<0.05). In conclusion, premature infants showed
higher cortisol levels - without a circadian rhythmicity - and higher activity
frequencies in the first days after birth which may reflect an adaptation process
of neonates after birth. Cortisol concentrations and the activity patterns were
not influenced by music interventions.
PMID- 25133794
TI - Effects of fenofibric acid on diabetic macular edema: the MacuFen study.
AB - PURPOSE: Fenofibrate reduced progression of diabetic retinopathy in two large
randomized studies. The effect of 135 mg fenofibric acid on diabetic macular
edema (DME) was evaluated in subjects with existing DME. METHODS: In this double
blind, randomized, placebo-controlled study, 110 subjects with DME not requiring
immediate photocoagulation or intraocular treatment with adequate diabetes and
blood pressure control received either fenofibric acid or placebo once daily for
1 year. Total macula volume (TMV) and thickness were measured in the worse eye
and all eligible eyes with time-domain optical coherence tomography at baseline
and quarterly thereafter. RESULTS: TMV decreased by -0.35 mm(3) (within-group
difference) after fenofibric acid treatment and by -0.11 mm(3) after placebo. The
between-group comparison of the change was -0.25 mm(3) (95% confidence interval,
CI, -0.645-0.155; p = 0.227, worse eye analysis). Weighted inner zone thickness
and volume decreased by -18.7 um and -0.13 mm(3), respectively, for within group
difference after fenofibric acid and by -3.1 um and -0.02 mm(3), respectively,
after placebo. Considering all eligible eyes, thicknesses at central zone, mean
inner zone, and entire retina decreased by -21.3 um, -19.8 um, and -20.4 um,
respectively, after fenofibric acid. No between-group difference in changes of
these measurements was observed. Triglycerides decreased by 23% after fenofibric
acid (vs 4% after placebo, p = 0.001) and high-density lipoprotein cholesterol
increased by 8% (vs 0.3%, p = 0.014). No safety concern was identified.
CONCLUSION: Subjects treated with fenofibric acid had a modest improvement in
TMV, although the study was probably underpowered to detect a benefit over
placebo after 1 year.
PMID- 25133796
TI - Application of rapid computer modeling in the analysis of the stabilization
method in intraoperative femoral bone shaft fracture during revision hip
arthroplasty - a case report.
AB - BACKGROUND: Fractures of the femoral bone shaft during and after hip arthroplasty
are a serious clinical problem. CASE REPORT: The paper presents the use of rapid
computer modeling FEM 2D to optimize the stabilization of femoral shaft fracture
in case of hip revision arthroplasty. CONCLUSIONS: Using the FEM modeling may be
helpful for planning and assessment of orthopaedic treatment in similar cases.
PMID- 25133797
TI - Isolated fracture of the hip stem prosthesis made of austenitic steel - a
literature review.
AB - Proper design and functioning of the hip joint ensure smooth motion over the full
range in multiple planes. Any change in this arrangement may lead to joint
damage, causing deformation, pain and loss of functionality. Hip replacement is a
procedure intended to replace the damaged articular surfaces and replacing them
with artificial components. However, as any surgical intervention, it carries the
risk of serious complications. One of them are isolated stem fractures,
consisting of breaking the implant inside the intramedullary canal without
damaging the surrounding tissue. This article contains a review of the literature
data concerning the clinical cases of isolated fractures of hip endoprosthesis
stems made of austenitic stainless steel. Although stem fractures are one of the
rarest complications of implantation, the lack of clear description of the causes
of this phenomenon in the literature makes it worthwhile to take up on the
subject.
PMID- 25133793
TI - Regenerative medicine for the heart: perspectives on stem-cell therapy.
AB - SIGNIFICANCE: Despite decades of progress in cardiovascular biology and medicine,
heart disease remains the leading cause of death, and there is no cure for the
failing heart. Since heart failure is mostly caused by loss or dysfunction of
cardiomyocytes (CMs), replacing dead or damaged CMs with new CMs might be an
ideal way to reverse the disease. However, the adult heart is composed mainly of
terminally differentiated CMs that have no significant self-regeneration
capacity. RECENT ADVANCES: Stem cells have tremendous regenerative potential and,
thus, current cardiac regenerative research has focused on developing stem cell
sources to repair damaged myocardium. CRITICAL ISSUES: In this review, we examine
the potential sources of cells that could be used for heart therapies, including
embryonic stem cells and induced pluripotent stem cells, as well as alternative
methods for activating the endogenous regenerative mechanisms of the heart via
transdifferentiation and cell reprogramming. We also discuss the current state of
knowledge of cell purification, delivery, and retention. FUTURE DIRECTIONS:
Efforts are underway to improve the current stem cell strategies and
methodologies, which will accelerate the development of innovative stem-cell
therapies for heart regeneration.
PMID- 25133798
TI - A long-term macroecological analysis of the recovery of a waterbird metacommunity
after site protection.
AB - We used the so called "land-bridge island" or "nested-subsets" theory to test the
resilience of a highly fragmented and perturbated waterbird metacommunity, after
legal protection of 18 wetlands in the western Mediterranean. Sites were
monitored during 28 years and two seasons per year. The metacommunity was
composed by 44 species during breeding and 67 species during wintering, including
shorebirds, ducks, herons, gulls and divers (Podicipedidae). We identified a
strong nested pattern. Consistent with the fact that the study system was to a
large extent a spatial biogeographical continuous for thousands of years,
fragmented only during the last centuries due to human activities. Non-random
selective extinction was the most likely historical process creating the nested
pattern, operated by the differential carrying capacity (surface-area) of the
remaining sites. We also found a positive temporal trend in nestedness and a
decreasing trend in species turnover among sites (beta-diversity), indicating
that sites are increasingly more alike to each other (i.e. increased biotic
homogenization). This decreasing trend in beta-diversity was explained by an
increasing trend in local (alpha) diversity by range expansion of half the study
species. Regional (gamma) diversity also increased over time, indicating that
colonization from outside the study system also occurred. Overall our results
suggest that the study metacommunity is recovering from historical anthropogenic
perturbations, showing a high long-term resilience, as expected for highly vagile
waterbirds. However, not all waterbird groups contributed equally to the
recovery, with most breeding shorebird species and most wintering duck species
showing no geographical expansion.
PMID- 25133799
TI - Improving facility performance in infectious disease care in Uganda: a mixed
design study with pre/post and cluster randomized trial components.
AB - BACKGROUND: The effects of two interventions, Integrated Management of Infectious
Disease (IMID) training program and On-Site Support (OSS), were tested on 23
facility performance indicators for emergency triage assessment and treatment
(ETAT), malaria, pneumonia, tuberculosis, and HIV. METHODS: The trial was
implemented in 36 primary care facilities in Uganda. From April 2010, two mid
level practitioners per facility participated in IMID training. Eighteen of 36
facilities were randomly assigned to Arm A, and received OSS in 2010 (nine
monthly two-day sessions); 18 facilities assigned to Arm B did not receive OSS in
2010. Data were collected from Nov 2009 to Dec 2010 using a revised Ministry of
Health outpatient medical form and nine registers. We analyzed the effect of IMID
training alone by measuring changes before and during IMID training in Arm B, the
combined effect of IMID training and OSS by measuring changes in Arm A, and the
incremental effect of OSS by comparing changes across Arms A and B. RESULTS: IMID
training was associated with statistically significant improvement in three
indicators: outpatients triaged (adjusted relative risks (aRR) = 1.29, 99%CI =
1.01,1.64), emergency and priority patients admitted, detained, or referred (aRR
= 1.59, 99%CI = 1.04,2.44), and pneumonia suspects assessed (aRR = 2.31, 99%CI =
1.50,3.55). IMID training and OSS combined was associated with improvements in
six indicators: three ETAT indicators (outpatients triaged (aRR = 2.03, 99%CI =
1.13,3.64), emergency and priority patients admitted, detained or referred (aRR =
3.03, 99%CI = 1.40,6.56), and emergency patients receiving at least one
appropriate treatment (aRR = 1.77, 99%CI = 1.10,2.84)); two malaria indicators
(malaria cases receiving appropriate antimalarial (aRR = 1.50, 99%CI =
1.04,2.17), and patients with negative malaria test results prescribed
antimalarial (aRR = 0.67, 99%CI = 0.46,0.97)); and enrollment in HIV care (aRR =
1.58, 99%CI = 1.32,1.89). OSS was associated with incremental improvement in
emergency patients receiving at least one appropriate treatment (adjusted ratio
of RR = 1.84,99%CI = 1.09,3.12). CONCLUSION: The trial showed that the OSS
intervention significantly improved performance in one of 23 facility indicators.
PMID- 25133800
TI - Evaluation of exome sequencing to estimate tumor burden in plasma.
AB - Accurate estimation of systemic tumor load from the blood of cancer patients has
enormous potential. One avenue is to measure the presence of cell-free
circulating tumor DNA in plasma. Various approaches have been investigated,
predominantly covering hotspot mutations or customized, patient-specific assays.
Therefore, we investigated the utility of using exome sequencing to monitor
circulating tumor DNA levels through the detection of single nucleotide variants
in plasma. Two technologies, claiming to offer efficient library preparation from
nanogram levels of DNA, were evaluated. This allowed us to estimate the
proportion of starting molecules measurable by sequence capture (<5%). As cell
free DNA is highly fragmented, we designed and provide software for efficient
identification of PCR duplicates in single-end libraries with a varying size
distribution. On average, this improved sequence coverage by 38% in comparison to
standard tools. By exploiting the redundant information in PCR-duplicates the
background noise was reduced to ~1/35,000. By applying our optimized analysis
pipeline to a simulation analysis, we determined the current sensitivity limit to
~1/2400, starting with 30 ng of cell-free DNA. Subsequently, circulating tumor
DNA levels were assessed in seven breast- and one prostate cancer patient. One
patient carried detectable levels of circulating tumor DNA, as verified by break
point specific PCR. These results demonstrate exome sequencing on cell-free DNA
to be a powerful tool for disease monitoring of metastatic cancers. To enable a
broad implementation in the diagnostic settings, the efficiency limitations of
sequence capture and the inherent noise levels of the Illumina sequencing
technology must be further improved.
PMID- 25133801
TI - Mechanisms of analgesic and anti-inflammatory properties of Annona muricata Linn.
(Annonaceae) fruit extract in rodents.
AB - Unripe fruit of Annona muricata Linn. (Annonaceae) (soursop) is used in
traditional African medicine for the treatment of neuralgia, rheumatism, and
arthritic pain. This study sought to investigate the analgesic and anti
inflammatory effects of lyophilized fruit extract of Annona muricata (AM) in
rodents. The analgesic activity was evaluated using the mouse writhing, formalin,
and hot-plate tests while the anti-inflammatory action was investigated using the
carrageenan-induced rat paw edema and xylene-induced ear edema tests.
Pretreatment with AM (50, 100, and 200 mg/kg, p.o.) produced dose-dependent
(P<.001) inhibition of writhes and formalin-induced pain in the late phase. AM
and morphine produced time-course increase in pain threshold in hot-plate test.
However, the analgesic effect elicited by AM was reversed (P<.05) by naloxone
pretreatment. Similarly, the time-dependent increase in paw circumference induced
by carrageenan was inhibited by AM treatment with peak effect (0.23+/-0.10 cm;
P<.001, 200 mg/kg; 6 h), which was comparatively similar to that of diclofenac
treated. Further, the xylene-induced ear edema was significantly reduced by AM
(50 or 100 mg/kg) pretreatment; however, the anti-inflammatory effect elicited by
AM was prevented by pretreatment of mice with N(G)-nitro-l-arginine (20 mg/kg,
i.p., nitric-oxide synthase inhibitor) 15 min before AM (200 mg/kg, p.o.). The in
vitro cyclooxygenase assay also showed that AM produced concentration-dependent
inhibition of both cyclooxygenase (COX)-1 and COX-2 activity by 39.44%+/-0.05%
and 55.71%+/-0.12%, respectively, at 100 MUg/mL. In conclusion, A. muricata
possesses analgesic effect through interaction with opioidergic pathway and anti
inflammatory property through inhibition of chemical mediators of inflammation.
PMID- 25133802
TI - Nanoparticle-based CT imaging technique for longitudinal and quantitative stem
cell tracking within the brain: application in neuropsychiatric disorders.
AB - A critical problem in the development and implementation of stem cell-based
therapy is the lack of reliable, noninvasive means to image and trace the cells
post-transplantation and evaluate their biodistribution, final fate, and
functionality. In this study, we developed a gold nanoparticle-based CT imaging
technique for longitudinal mesenchymal stem cell (MSC) tracking within the brain.
We applied this technique for noninvasive monitoring of MSCs transplanted in a
rat model for depression. Our research reveals that cell therapy is a potential
approach for treating neuropsychiatric disorders. Our results, which demonstrate
that cell migration could be detected as early as 24 h and up to one month post
transplantation, revealed that MSCs specifically navigated and homed to distinct
depression-related brain regions. We further developed a noninvasive quantitative
CT ruler, which can be used to determine the number of cells residing in a
specific brain region, without tissue destruction or animal scarification. This
technique may have a transformative effect on cellular therapy, both for basic
research and clinical applications.
PMID- 25133803
TI - The integrated disease network.
AB - The growing body of transcriptomic, proteomic, metabolomic and genomic data
generated from disease states provides a great opportunity to improve our current
understanding of the molecular mechanisms driving diseases and shared between
diseases. The use of both clinical and molecular phenotypes will lead to better
disease understanding and classification. In this study, we set out to gain novel
insights into diseases and their relationships by utilising knowledge gained from
system-level molecular data. We integrated different types of biological data
including genome-wide association studies data, disease-chemical associations,
biological pathways and Gene Ontology annotations into an Integrated Disease
Network (IDN), a heterogeneous network where nodes are bio-entities and edges
between nodes represent their associations. We also introduced a novel disease
similarity measure to infer disease-disease associations from the IDN. Our
predicted associations were systemically evaluated against the Medical Subject
Heading classification and a statistical measure of disease co-occurrence in
PubMed. The strong correlation between our predictions and co-occurrence
associations indicated the ability of our approach to recover known disease
associations. Furthermore, we presented a case study of Crohn's disease. We
demonstrated that our approach not only identified well-established connections
between Crohn's disease and other diseases, but also revealed new, interesting
connections consistent with emerging literature. Our approach also enabled ready
access to the knowledge supporting these new connections, making this a powerful
approach for exploring connections between diseases.
PMID- 25133805
TI - Helical versus all-trans conformations of oligo(ethylene glycol)-terminated
alkanethiol self-assembled monolayers.
AB - The complex mixture of conformational states exhibited by oligo(ethylene glycol)
terminated alkanethiols on Ag and Au surfaces is explored by polarization
dependent X-ray absorption spectroscopy. Three self-assembled monolayers (SAMs)
with known helical or all-trans conformations are used as references to
characterize a SAM with unknown conformations. This case study is used as a
prototype for developing a systematic framework to extract the conformations of
SAMs from the polarization dependence of several orbitals. In the case at hand,
these are associated with the C-H/Rydberg bonds of the alkane, the C-H/Rydberg
bonds of ethylene glycol, and the C-C bonds of the backbone. The C-H/Rydberg
orbitals of the alkane and ethylene glycol are distinguished via the chemical
shift of the corresponding C 1s core levels.
PMID- 25133804
TI - Contrasting metabolism in perenniating structures of upland and lowland
switchgrass plants late in the growing season.
AB - BACKGROUND: Switchgrass (Panicum virgatum L.) is being developed as a bioenergy
crop for many temperate regions of the world. One way to increase biomass yields
is to move southern adapted lowland cultivars to more northern latitudes.
However, many southerly adapted switchgrass germplasm can suffer significant
winter kill in northerly climes. MATERIALS AND METHODS: Here, we have applied
next-generation sequencing in combination with biochemical analyses to query the
metabolism of crowns and rhizomes obtained from two contrasting switchgrass
cultivars. Crowns and rhizomes from field-grown lowland (cv Kanlow) and upland
(cv Summer) switchgrass cultivars were collected from three randomly selected
post-flowering plants. Summer plants were senescing, whereas Kanlow plants were
not at this harvest date. RESULTS: Principal component analysis (PCA)
differentiated between both the Summer and Kanlow transcriptomes and metabolomes.
Significant differences in transcript abundances were detected for 8,050 genes,
including transcription factors such as WRKYs and those associated with
phenylpropanoid biosynthesis. Gene-set enrichment analyses showed that a number
of pathways were differentially up-regulated in the two populations. For both
populations, protein levels and enzyme activities agreed well with transcript
abundances for genes involved in the phenylpropanoid pathway that were up
regulated in Kanlow crowns and rhizomes. The combination of these datasets
suggests that dormancy-related mechanisms had been triggered in the crowns and
rhizomes of the Summer plants, whereas the crowns and rhizomes of Kanlow plants
had yet to enter dormancy. CONCLUSIONS: Delayed establishment of dormancy at more
northerly latitudes could be one factor that reduces winter-survival in the high
yielding Kanlow plants. Understanding the cellular signatures that accompany the
transition to dormancy can be used in the future to select plants with improved
winter hardiness.
PMID- 25133806
TI - [Changes in the newest recommendations on Asthma Management and Prevention - GINA
Report 2014. What should we pay attention to?].
PMID- 25133807
TI - Epidemiological situation of tuberculosis in Poland: part II. What are the causes
of the different epidemiological situation in various regions of Poland?
AB - INTRODUCTION: The different epidemiological situation of tuberculosis in various
regions of Poland (higher and lower notification rates) was described previously
by our group. The patients diagnosed with tuberculosis in the higher notification
rate areas were younger and there were more cases of primary tuberculosis
(tuberculous pleurisy and tuberculosis of chest lymph nodes) than in the patients
diagnosed in the lower notification areas. The aim of the present study was to
assess the possible causes of the different epidemiological situation of
tuberculosis in various regions of Poland. MATERIAL AND METHODS: Analysis was
done at the same regions as in the previous paper. A comparison was made between
two groups: Group I, which included three voivodeships with higher rates of
notification, from 23.7 to 32.3/100,000 (mean rates in the analysed period of
time); and Group II, which included five voivodeships with lower notification
rates (mean rates from 12.2 to 18.6/100,000). The wealth of the regions (GDP,
gross domestic product per capita), the level of unemployment, and social status
of the patients were analysed. We compared the population density in both
regions. The results of treatment in both regions were also analysed. RESULTS: We
did not find any differences in GDP and unemployment rates between the compared
regions. The results of treatment were different in particular regions, but there
was no clear tendency for worse results in voivodeships in Group I compared to
voivodeships in Group II. However, the number of patients lost from observation
was significantly higher in the regions from Group I than in those from Group II.
There was also a significantly higher death rate from tuberculosis in younger
patients (L 59 years) from Group I than from Group II. This is additional proof
that the epidemiological situation in the two regions was different. Finally, we
found that the mean density of population in the regions from Group I was higher
than that from Group II. The density of population may influence transmission of
tuberculosis. There is also the possibility that the differences in the
epidemiological situation in various regions of Poland are caused by historical
events. In the past the epidemiological situation of tuberculosis was much worse
in the east of Europe than in the west. Just after the Second World War,
according to the changes of the Polish territory, many Polish citizens (mainly
ancestors of those from Group I) were displaced from the east to the west.
CONCLUSIONS: In conclusion, the greater number of patients lost from observation,
together with the higher density of population in the regions from Group I in
comparison with those from Group II, seems to be partly responsible for the
difference in the epidemiological situation in the two regions. It is also
possible that some patients from Group I are more susceptible to infection and
disease caused by Mycobacterium tuberculosis due to their ancestors, who lived in
the east of Europe.
PMID- 25133808
TI - Bronchoscopy in immediate diagnosis of smear negative tuberculosis.
AB - BACKGROUND: Tuberculosis is a major public health problem. Almost 30% of cases of
tuberculosis are known to be sputum smear negative. There is a diagnostic dilemma
in such cases leading to inadvertent delays in management of these cases. The
present study was planned to assess the role of bronchoscopy in immediate
diagnosis of smear negative pulmonary tuberculosis. MATERIAL AND METHODS: The
present study is a retrospective analysis of 132 sputum smear negative
tuberculosis suspects who underwent bronchoscopic evaluation during the period
2002-2013. The diagnosis of tuberculosis was based on the finding of bacilli in
aspirate or in tissue biopsy or the demonstration of caseous necrosis on tissue
biopsy. RESULTS: The present study showed that bronchoscopy could lead to
immediate, accurate diagnosis in 68.2% of suspected smear negative cases.
Bronchial aspirate and bronchoalveolar lavage alone were diagnostic in 51.5% of
such cases while tissue biopsy added to the yield in another 16.5% cases.
CONCLUSIONS: The results of the present study suggests an important place of
bronchoscopy in immediate diagnosis of suspected smear negative tuberculosis,
thus avoiding inadvertent delays in diagnosing and instituting appropriate
treatment.
PMID- 25133809
TI - Stratification of patients with COPD according to the 2011 GOLD report.
AB - INTRODUCTION: The authors aimed to compare the distribution of COPD based on the
new GOLD grading with stadium based exclusively on spirometry. MATERIAL AND
METHODS: Eligible patients had an average age of 64.8 years and smoked at least
10 pack-years. COPD was defined according to GOLD fixed cut-off criterion
FEV1/FVC < 0.70. In all patients postbronchodilator spirometry was performed.
Categories were defined with the mMRC dyspnoea scale and CAT scale. COPD
exacerbations in the previous year and lung function were evaluated. Statistical
comparisons were done using t-student test. RESULTS: 315 COPD patients, 99
(31.4%) women and 216 (68.6%) men, were examined. Mean pack-years in the whole
group was 47.1 +/- 17.8. In women this figure was less than in men, 43.7 +/- 19.2
vs 49.5 +/- 16.5 (p > 0.05), respectively. At study entry, 144 subjects (45.7%)
were current smokers, and the majority of them (n-87, 60.4%) belonged to category
D - 26/66 (54.5%) women and 51/102 (50%) men. Based on spirometry alone, the
patients were classified as moderate COPD 144 (45.71%), severe - 154 (48.89%),
and very severe 17 (5.4%). According to the 2011 GOLD report stratification, 60
patients (19.04%) were graded as category A, 63 (20%) as category B, 24 (7.62%)
as category C, and 168 (53.33%) as category D, although 21 (12.5% of them) were
in category B, but the number of exacerbations classified them as category D.
CONCLUSIONS: The COPD population is heterogeneous in reference to the symptoms,
value of FEV1, and susceptibility to exacerbations. Clinical symptoms assessed
using validated questionnaires characterized COPD patients better than the value
of spirometric parameters (which are necessary for diagnosis of this disease).
Some patients were difficult to classify, especially those belonging to category
C.
PMID- 25133810
TI - Prognostic value of serum C-reactive protein (CRP) and cytokeratin 19 fragments
(Cyfra 21-1) but not carcinoembryonic antigen (CEA) in surgically treated
patients with non-small cell lung cancer.
AB - INTRODUCTION: The aim of the study was to assess the prognostic value of
cytokeratin 19 fragments (Cyfra 21-1), carcinoembryonic antigen (CEA) and C
reactive protein (CRP) in surgically treated NSCLC patients. MATERIAL AND
METHODS: 50 NSCLC patients (25 adenocarcinoma, 21 squamous cell and 4
adenosquamous), clinical stages I and II, age 42-89 years, entered the study.
CEA, Cyfra 21-1 and CRP concentrations were measured in serum taken before
surgery, CEA and Cyfra 21-1 in 50 patients, CRP - in 46 patients. The survival
was calculated from the date of surgical treatment until death or until the end
of the observation time. The results were expressed as medians (95%CI). RESULTS:
Cyfra 21-1 concentration was 2.1 (0.7-14.5) ng/mL. Survival time in the patients
with Cyfra 21-1 <= 2 ng/mL, and > 2 ng/ /mL was 79 (14.85-88.2) and 29 (5.7-87.6)
months, (p < 0.026). CEA concentration was 2.68 (0.87-72.7) ng/mL, significantly
higher in adenocarcinoma than in squamous cell lung cancer - 4.38 ng/mL (1.67
41.35) vs. 2.2 ng/mL (1.0-6.1), p = 0.002. CRP concentration was 5.45 (0-122.6)
mg/L. Significant dependence was found between CRP and pathological tumour size
(pT). Median CRP values in pT1, pT2 and pT3+4 tumours were: 2.8 mg/L, 6.9 mg/L
and 23.5 mg/L, respectively. Survival time of the patients with CRP <= 10 mg/L
and CRP > 10 mg/L was 79 (14.85-88.2) and 29.5 (5.7-87.6) months, respectively (p
= 0.045). CRP > 10 mg/L and Cyfra 21-1 > 2 ng/mL were the only significant
preoperative prognostic indicators (HR 2.08 and 2.04, respectively). Among the
postoperative parameters, pathological stage of disease (p-stage) and pT were the
significant prognostic indicators (HR 2.1 and 2.42, respectively). CONCLUSIONS:
In the present study, concerning surgically treated NSCLC patients, preoperative
CRP > 10 mg/L and Cyfra 21-1 > 2 ng/mL were the only negative prognostic
indicators, while pT and p-stage were significant postoperative prognostic
indicators.
PMID- 25133811
TI - Detecting Mycobacterium tuberculosis complex DNA, based on post-mortem
examination of hilar lymph nodes with real-time PCR: initial study.
AB - INTRODUCTION: According to the WHO, almost a third of the world population are
thought to be infected with Mycobacterium tuberculosis. Some studies of the
prevalence of latent tuberculosis infection (LTBI) have already been performed in
Poland, showing that almost a quarter of the Mazovia population could be
infected. It also indicated a higher prevalence of LTBI among seniors. Those
studies were based on indirect diagnostic methods. MATERIAL AND METHODS: We
randomly collected hilar lymph nodes from decedents aged 40 years and older
during post-mortem examination. We excluded patients with previous confirmed
tuberculosis. In addition, an autopsy was performed in all patients. Finally, we
used real-time PCR Xpert MTB/RIF (Cepheid, USA) for the specific capture of
mycobacterial DNA. RESULTS: Twenty-two of 23 patients had a negative result of
the real-time PCR examination and no signs of caseous necrosis in hilar lymph
nodes. We found the only positive sample in a patient with histopathological
signs of tuberculosis (the presence of caseous necrosis in the specimens obtained
from lymph nodes and lung). Due to the change of cartridges from version G3 to
G4, further reactions were inhibited and no more post-mortem samples were tested.
CONCLUSIONS: Real-time PCR Xpert MTB/RIF was capable of detecting M. tuberculosis
complex DNA in a patient with tuberculosis recognised on autopsy. In the
remaining patients, no M. tuberculosis complex DNA was found, in accordance with
negative results of histological examination. Since the technology of cartridges
has changed, it is no longer possible to use real-time PCR Xpert MTB/RIF (Cepheid
USA) on post-mortem material.
PMID- 25133812
TI - Methodological recommendations for the diagnostics of EGFR gene mutations and ALK
gene rearrangement in the selection of non-small-cell lung cancer patients to
molecularly targeted therapies.
AB - Testing for EGFR gene mutations and ALK gene rearrangement is routinely used in
advanced non-small-cell lung cancer for adequate patient selection to molecularly
targeted therapies. We present Polish methodological recommendations for
molecular analysis of EGFR and ALK genetic abnormalities. Recommendations specify
clinical indications for testing, sample types and handling, as well as
requirements for laboratories performing molecular diagnostics.
PMID- 25133813
TI - Immediate hypersensitivity reaction with mango.
AB - Hypersensitivity to the fruit mango is extremely rare and can exhibit either as
immediate or delayed reactions. Since 1939, only 22 patients (10 with immediate
type I reactions and 12 with delayed) have been documented with allergy to mango.
History of atopy and geographical region may influence the type of reaction.
Immediate reactions occurred most often in patients with history of atopy, while
delayed reactions developed in non-atopic individuals. Clustering of delayed
hypersensitivity reports from Australia and immediate reactions from Europe has
been documented. We report a 50-year-old man with immediate type I
hypersensitivity to mango, who developed cough, wheezing dyspnoea, generalised
itching and abdominal discomfort after ingestion of mango. Life threatening event
can also happen making it imperative to diagnose on time, so as to prevent
significant morbidity and potential mortality.
PMID- 25133815
TI - [Pneumocystis pneumonia in HIV-infected patients with cytomegalovirus co
infection. Two case reports and a literature review].
AB - Pneumocystis pneumonia (PCP) is one of the infectious lung diseases diagnosed in
HIV-infected patients. The pathogen responsible for the development of this
opportunistic infection is an atypical fungus called Pneumocystis jiroveci. PCP
remains the most common disorder diagnosed at the onset of acquired
immunodeficiency syndrome (AIDS), especially in individuals not aware of their
HIV infection. The most important risk factor of PCP development in HIV-infected
person is the decrease of T CD4+ cell number below 200/mcL. Clinical symptoms
consist of: chronic cough, dyspnoea and weakness. Arterial blood gas analysis
often reveals the presence of hypoxaemia, and high-resolution computed tomography
imaging shows diffuse ground glass opacities. Treatment is based on intravenous
administration of trimetoprim-sulfamethoxasole. In patients with moderate and
severe symptoms of PCP it is recommended that corticosteroids are used. Co
infection with cytomegalovirus (CMV) is a poor prognostic sign in PCP. CMV
related organ disease should be suspected in patients with T CD4+ cell number
lower than 50/mcL. It is arguable whether CMV infection in symptomatic PCP
patients should be treated. There are suggestions that corticosteroids used in
PCP patients with CMV co-infection could promote the development of CMV
pneumonia. In the present paper we present two patients with PCP, unaware of
their HIV infection. In both cases a CMV co-infection was found.
PMID- 25133814
TI - Granulomatosis with polyangiitis (Wegener's granulomatosis) with hard palate and
bronchial perforations treated with rituximab - a case report.
AB - We present a case of a 57-year-old woman suffering from granulomatosis with
polyangiitis (GPA), who in the seventh months of immunosuppressive treatment
(cyclophosphamide) progressed with new pulmonary changes and perforations of the
hard palate and bronchi. Rituximab was introduced resulting in B-cell depletion
and disappearance of anti-PR3 antibody. Palatal holes have substantially
diminished and all bronchial perforations disappeared, covered by fibrous tissue.
In the fourth month after rituximab administration, large scarring obstruction of
the right main bronchus with upper and middle lobes atelectasis emerged. Because
of increasing dyspnoea, stenotic bronchus was re-opened by bronchoscopy.
Intervention was complicated by bilateral pneumothorax and later, on the seventh
day, by fatal pulmonary bleeding. To our knowledge, this is the first report of
GPA refractory to cyclophosphamide complicated by palatal and bronchial
perforations.
PMID- 25133816
TI - [Exercise-induced urticaria and angioedema - case report].
AB - Urticaria is a heterogeneous group of disorders, with various clinical
manifestations and intensity of symptoms. Urticaria can be induced with a wide
variety of environmental stimuli, such as cold, pressure, vibration, sunlight,
exercise, temperature changes, heat, and water. In a select group of patients,
exercise can induce a spectrum of urticaria symptoms, ranging from cutaneous
pruritus and warmth, generalised urticaria, angioedema, and the appearance of
such additional manifestations as collapse, upper respiratory distress, and
anaphylaxis. Specific provocation tests should be carried out on an individual
basis to investigate the suspected cause and proper diagnosis. Modification of
activities and behaviour is the mainstay of treatment in patients with physical
urticaria. The aim of this study was to emphasise that primary care
paediatricians should be able to recognise physical urticaria, supply a patient
with rescue medications, and refer him/her to a specialist. In the article, the
authors present a 13-year-old girl with typical urticaria lesions and angioedema
after exercise. According to the history, physical examination, and provocation
test, exercise-induced urticaria and angioedema were diagnosed.
PMID- 25133817
TI - [Ventilator-associated pneumonia and other infections].
AB - One of the fundamental elements of therapy in patients hospitalised in the
Intensive Care Unit (ICU) is mechanical ventilation (MV). MV enables sufficient
gas exchange in patients with severe respiratory insufficiency, thus preserving
the proper functioning of organs and systems. However, clinical and experimental
studies show that mechanical ventilation may cause severe complications, e.g.
lung injury (VALI, VILI), systemic inflammatory response syndrome (SIRS), and, on
rare occasions, multiple organ failure (MOF). Mechanical ventilation and
especially endotracheal intubation are associated also with higher risk of
infectious complications of the respiratory system: ventilator-associated
respiratory infection (VARI) and ventilator-associated pneumonia (VAP). The
complications of the MV listed above have a significant influence on the length
of treatment and also on the increase of the costs of therapy and mortality of
patients who stay in an ICU. These negative effects of supported breathing are
the reasons for intensive research to find new biological markers of inflammation
and lung injury, more sensitive and specific diagnostic instruments, more
effective methods of therapy, and programs of prevention. The purpose of this
article is the presentation of current knowledge concerning VAP-related
infections, to allow pulmonologists and general practitioners to become more
familiar with the problem. Basic and the most important data concerning the
definition, epidemiology, pathophysiology, microbiology, diagnostics, treatment,
and prevention of VAP have been included. Additionally, ventilator-associated
tracheobronchitis (VAT) was discussed.
PMID- 25133818
TI - Phylogeny in defining model plants for lignocellulosic ethanol production: a
comparative study of Brachypodium distachyon, wheat, maize, and Miscanthus x
giganteus leaf and stem biomass.
AB - The production of ethanol from pretreated plant biomass during fermentation is a
strategy to mitigate climate change by substituting fossil fuels. However,
biomass conversion is mainly limited by the recalcitrant nature of the plant cell
wall. To overcome recalcitrance, the optimization of the plant cell wall for
subsequent processing is a promising approach. Based on their phylogenetic
proximity to existing and emerging energy crops, model plants have been proposed
to study bioenergy-related cell wall biochemistry. One example is Brachypodium
distachyon, which has been considered as a general model plant for cell wall
analysis in grasses. To test whether relative phylogenetic proximity would be
sufficient to qualify as a model plant not only for cell wall composition but
also for the complete process leading to bioethanol production, we compared the
processing of leaf and stem biomass from the C3 grasses B. distachyon and
Triticum aestivum (wheat) with the C4 grasses Zea mays (maize) and Miscanthus x
giganteus, a perennial energy crop. Lambda scanning with a confocal laser
scanning microscope allowed a rapid qualitative analysis of biomass
saccharification. A maximum of 108-117 mg ethanol.g(-1) dry biomass was yielded
from thermo-chemically and enzymatically pretreated stem biomass of the tested
plant species. Principal component analysis revealed that a relatively strong
correlation between similarities in lignocellulosic ethanol production and
phylogenetic relation was only given for stem and leaf biomass of the two tested
C4 grasses. Our results suggest that suitability of B. distachyon as a model
plant for biomass conversion of energy crops has to be specifically tested based
on applied processing parameters and biomass tissue type.
PMID- 25133821
TI - Enantioselective C-H bond addition of pyridines to alkenes catalyzed by chiral
half-sandwich rare-earth complexes.
AB - Cationic half-sandwich scandium alkyl complexes bearing monocyclopentadienyl
ligands embedded in chiral binaphthyl backbones act as excellent catalysts for
the enantioselective C-H bond addition of pyridines to various 1-alkenes, leading
to formation of a variety of enantioenriched alkylated pyridine derivatives in
high yields and excellent enantioselectivity (up to 98:2 er).
PMID- 25133819
TI - Effect of late planting and shading on cellulose synthesis during cotton fiber
secondary wall development.
AB - Cotton-rapeseed or cotton-wheat double cropping systems are popular in the
Yangtze River Valley and Yellow River Valley of China. Due to the competition of
temperature and light resources during the growing season of double cropping
system, cotton is generally late-germinating and late-maturing and has to suffer
from the coupling of declining temperature and low light especially in the late
growth stage. In this study, late planting (LP) and shading were used to fit the
coupling stress, and the coupling effect on fiber cellulose synthesis was
investigated. Two cotton (Gossypium hirsutum L.) cultivars were grown in the
field in 2010 and 2011 at three planting dates (25 April, 25 May and 10 June)
each with three shading levels (normal light, declined 20% and 40% PAR). Mean
daily minimum temperature was the primary environmental factor affected by LP.
The coupling of LP and shading (decreased cellulose content by 7.8%-25.5%)
produced more severe impacts on cellulose synthesis than either stress alone, and
the effect of LP (decreased cellulose content by 6.7%-20.9%) was greater than
shading (decreased cellulose content by 0.7%-5.6%). The coupling of LP and
shading hindered the flux from sucrose to cellulose by affecting the activities
of related cellulose synthesis enzymes. Fiber cellulose synthase genes expression
were delayed under not only LP but shading, and the coupling of LP and shading
markedly postponed and even restrained its expression. The decline of sucrose
phosphate synthase activity and its peak delay may cause cellulose synthesis
being more sensitive to the coupling stress during the later stage of fiber
secondary wall development (38-45 days post-anthesis). The sensitive difference
of cellulose synthesis between two cultivars in response to the coupling of LP
and shading may be mainly determined by the sensitiveness of invertase, sucrose
phosphate synthase and cellulose synthase.
PMID- 25133820
TI - The Ca2+ sensor protein swiprosin-1/EFhd2 is present in neurites and involved in
kinesin-mediated transport in neurons.
AB - Swiprosin-1/EFhd2 (EFhd2) is a cytoskeletal Ca2+ sensor protein strongly
expressed in the brain. It has been shown to interact with mutant tau, which can
promote neurodegeneration, but nothing is known about the physiological function
of EFhd2 in the nervous system. To elucidate this question, we analyzed EFhd2-/
/lacZ reporter mice and showed that lacZ was strongly expressed in the cortex,
the dentate gyrus, the CA1 and CA2 regions of the hippocampus, the thalamus, and
the olfactory bulb. Immunohistochemistry and western blotting confirmed this
pattern and revealed expression of EFhd2 during neuronal maturation. In cortical
neurons, EFhd2 was detected in neurites marked by MAP2 and co-localized with pre-
and post-synaptic markers. Approximately one third of EFhd2 associated with a
biochemically isolated synaptosome preparation. There, EFhd2 was mostly confined
to the cytosolic and plasma membrane fractions. Both synaptic endocytosis and
exocytosis in primary hippocampal EFhd2-/- neurons were unaltered but transport
of synaptophysin-GFP containing vesicles was enhanced in EFhd2-/- primary
hippocampal neurons, and notably, EFhd2 inhibited kinesin mediated microtubule
gliding. Therefore, we found that EFhd2 is a neuronal protein that interferes
with kinesin-mediated transport.
PMID- 25133822
TI - Financial incentives for increasing uptake of HPV vaccinations: a randomized
controlled trial.
AB - OBJECTIVE: Uptake of human papillomavirus (HPV) vaccinations by 17- to 18-year
old girls in England is below (<35%) target (80%). This trial assesses (a) the
impact of financial incentives on uptake and completion of an HPV vaccination
program, and (b) whether impacts are moderated by participants' deprivation
level. It also assesses the impact of incentives on decision quality to get
vaccinated, as measured by attitudes toward the vaccination and knowledge of its
consequences. METHOD: One thousand 16- to 18-year-old girls were invited to
participate in an HPV vaccination program: 500 previously uninvited, and 500
unresponsive to previous invitations. Girls randomly received either a standard
invitation letter or a letter including the offer of vouchers worth L 45 (? 56;
$73) for undergoing 3 vaccinations. Girls attending their first vaccination
appointment completed a questionnaire assessing decision quality to be
vaccinated. Outcomes were uptake of the first and third vaccinations and decision
quality. RESULTS: The intervention increased uptake of the first (first-time
invitees: 28.4% vs. 19.6%, odds ratio [OR] = 1.63, 95% confidence interval [CI;
1.08, 2.47]; previous nonattenders: 23.6% vs. 10.4%, OR = 2.65, 95% CI [1.61,
4.38]) and third (first-time invitees: 22.4% vs. 12%, OR = 2.15, 95% CI [1.32,
3.50]; previous nonattenders: 12.4% vs. 3%, OR = 4.28, 95% CI [1.92, 9.55])
vaccinations. Impacts were not moderated by deprivation level. Decision quality
was unaffected by the intervention. CONCLUSIONS: Although the intervention
increased completion of HPV vaccinations, uptake remained lower than the national
target, which, in addition to cost effectiveness and acceptability issues,
necessitates consideration of other ways of achieving it.
PMID- 25133823
TI - Negative appearance evaluation is associated with skin cancer risk behaviors
among American men and women.
AB - OBJECTIVE: The current study aimed to examine links between appearance evaluation
and skin cancer risk behaviors in men and women. METHOD: Data (N = 1,535; men, n
= 873; women, n = 662) were extracted from Wave 4 of the National Longitudinal
Study of Adolescent Health, a nationally representative, longitudinal dataset of
U.S. adolescents and young adults. RESULTS: Skin cancer risk (i.e., number of
hours spent outside for those with a history of severe sunburn and who were
unlikely to use sunscreen) was significantly associated with participant gender,
appearance evaluation, and their interaction. Both men and women who negatively
evaluated their appearance were at significantly increased skin cancer risk, and
this was particularly true for men. CONCLUSIONS: Negative appearance evaluation
appears to be a correlate of engaging in behaviors that place individuals at risk
of developing skin cancer. Future research may benefit from skin cancer
prevention interventions that directly address appearance-based evaluations.
PMID- 25133824
TI - Associations between socioeconomic status and obesity in diverse, young
adolescents: variation across race/ethnicity and gender.
AB - OBJECTIVE: This study examined the association between socioeconomic status (SES)
and obesity risk during early adolescence, ages 10-13 years, and whether this
association is present in different racial/ethnic and gender groups during 2 time
points in early adolescence. METHOD: Data were from the Healthy Passages study,
which enrolled 4,824 African American, Hispanic, and White 5th graders (ages 10
11) in a population-based, longitudinal study conducted in 3 U.S. metropolitan
areas, and assessed them again 2 years later. Weight status was classified from
measured body mass index using standard criteria into nonobese and obese (27% in
5th grade). SES was indexed based on highest education attainment in the
household. RESULTS: Youth in the highest SES had a significantly lower prevalence
of obesity than those of lower SES at both 5th and 7th grades when disregarding
race/ethnicity. Within-racial/ethnic group analyses mostly confirmed this pattern
for Hispanic and White youth, but not for African American youth. When also
considering gender, the SES differential in obesity risk was more pronounced
among White girls and 5th-grade Hispanic boys. CONCLUSION: Growing up in a high
SES home, marked by having a member with at least a college degree, is associated
with lower risk for obesity among Hispanic and White youth. For African American
youth, there appears to be no association between SES and obesity. Thus the
health advantage generally attributed to higher SES does not appear consistently
across racial/ethnic groups for obesity in youth. Further research should
identify influences on weight status beyond SES, especially among African
American youth.
PMID- 25133825
TI - Short-term affective recovery from hip fracture prospectively predicts depression
and physical functioning.
AB - OBJECTIVE: The goals of the current study were to determine the average affective
experiences in the weeks and months after a hip fracture and assess how these
experiences relate to physical and mental health functioning over time. METHOD:
Positive and negative affect were assessed over time in a sample of older adults
recruited after surgery for hip fracture (n = 500) and a comparison sample of
older adults without hip fracture (n = 102) for 1 year longitudinally. RESULTS:
For most of the individuals with a hip fracture, positive affect tended to
increase over time and negative affect tended to decrease over time, suggesting
that most people had at least some recovery of affect. In addition, individuals
who showed a slower decrease in negative affect had higher levels of depression 1
year later, and individuals who showed a sharper increase in positive affect had
superior physical function 1 year later. CONCLUSION: The current study provides
evidence that both positive and negative affect in the first 12 weeks of recovery
from hip fracture are potential targets for intervention to maximize
psychological and physical recovery in the ensuing year.
PMID- 25133826
TI - The association of metacognitive beliefs with emotional distress after diagnosis
of cancer.
AB - OBJECTIVE: Emotional distress after a diagnosis of cancer is normal and, for most
people, will diminish over time. However, a significant minority of patients with
cancer experience persistent or recurrent symptoms of emotional distress for
which they need help. A model developed in mental health, the self-regulatory
executive function model (S-REF), specifies that maladaptive metacognitive
beliefs and processes, including persistent worry, are key to understanding why
such emotional problems persist. This cross-sectional study explored, for the
first, time whether metacognitive beliefs were associated with emotional distress
in a cancer population, and whether this relationship was mediated by worry, as
predicted by the S-REF model. METHOD: Two hundred twenty-nine participants within
3 months of diagnosis of, and before treatment for, primary breast or prostate
cancer completed self-report questionnaires measuring anxiety, depression,
posttraumatic stress disorder (PTSD) symptoms, metacognitive beliefs, worry, and
illness perceptions. RESULTS: Regression analysis showed that metacognitive
beliefs were associated with symptoms of anxiety, depression, and PTSD, and
explained additional variance in these outcomes after controlling for age,
gender, and illness perceptions. Structural equation modeling was consistent with
cross-sectional hypotheses derived from the theory that metacognitive beliefs
cause and maintain distress both directly and indirectly by driving worry.
CONCLUSIONS: The findings provide promising first evidence that the S-REF model
may be usefully applied in cancer. Further study is required to establish the
predictive and clinical utility of these findings.
PMID- 25133827
TI - Does the early feedback of results improve reassurance following diagnostic
testing? A randomized controlled trial in patients undergoing cardiac
investigation.
AB - OBJECTIVE: Providing reassurance is often a critical component of the medical
consultation. An important area that has not been addressed in the literature is
how delay in providing the results of medical tests affects patient reassurance.
In this study we investigated whether the early provision of a normal diagnostic
result immediately following medical testing improves patient reassurance
compared to results provided 4 weeks later. METHOD: We conducted a longitudinal
randomized controlled trial and 1-month follow-up. Fifty-one cardiology
outpatients with no known cardiac pathology referred for an echocardiogram test
were randomized following normal test results to receive their test results from
a cardiologist either immediately following testing or 4 weeks later. Measures of
symptoms, anxiety, and health perceptions were taken prior to diagnostic testing.
Reassurance was assessed immediately after the results were provided and 1 month
later. RESULTS: Data analysis showed that the provision of early results had no
impact on patient reassurance. Cardiac anxiety was strongly associated with lower
reassurance; patients who were more anxious about their heart were significantly
less reassured by a normal test result, both immediately following feedback and 1
month later. CONCLUSIONS: The early provision of test results had no impact on
patient reassurance. The study suggests the identification and targeting of
patients high in cardiac anxiety may be a better method for improving reassurance
than reducing the waiting time for results following medical testing.
PMID- 25133828
TI - Adolescent sexual health communication and condom use: a meta-analysis.
AB - OBJECTIVE: Condom use is critical for the health of sexually active adolescents,
and yet many adolescents fail to use condoms consistently. One interpersonal
factor that may be key to condom use is sexual communication between sexual
partners; however, the association between communication and condom use has
varied considerably in prior studies of youth. The purpose of this meta-analysis
was to synthesize the growing body of research linking adolescents' sexual
communication to condom use, and to examine several moderators of this
association. METHOD: A total of 41 independent effect sizes from 34 studies with
15,046 adolescent participants (M(age) = 16.8, age range = 12-23) were meta
analyzed. RESULTS: Results revealed a weighted mean effect size of the sexual
communication-condom use relationship of r = .24, which was statistically
heterogeneous (Q = 618.86, p < .001, I2 = 93.54). Effect sizes did not differ
significantly by gender, age, recruitment setting, country of study, or condom
measurement timeframe; however, communication topic and communication format were
statistically significant moderators (p < .001). Larger effect sizes were found
for communication about condom use (r = .34) than communication about sexual
history (r = .15) or general safer sex topics (r = .14). Effect sizes were also
larger for communication behavior formats (r = .27) and self-efficacy formats (r
= .28), than for fear/concern (r = .18), future intention (r = .15), or
communication comfort (r = -.15) formats. CONCLUSIONS: Results highlight the
urgency of emphasizing communication skills, particularly about condom use, in
HIV/STI prevention work for youth. Implications for the future study of sexual
communication are discussed.
PMID- 25133831
TI - Narrative as a knowledge translation tool for facilitating impact: translating
physical activity knowledge to disabled people and health professionals.
AB - OBJECTIVE: Theoretically informed by narrative inquiry, this article examines the
utility of stories as a possible tool for disseminating synthesized physical
activity knowledge to adults with spinal cord injury (SCI) and health care
professionals (HCPs) working with this population. It is the first research to
systematically examine in this context the use of narratives as a knowledge
translation tool. METHOD: Forty-three participants (15 adults with SCI; 13 peer
mentors with SCI; and 15 HCPs) individually listened to an evidence-based story
set in a rehabilitation hospital about the process of becoming physically active
following SCI. Individual telephone interviews were conducted to examine
participants' perceptions of the story. Qualitative data were analyzed using a
thematic analysis. RESULTS: Five themes were inductively identified: (a)
effective communication, (b) narrative authenticity, (c) credible messengers, (d)
narrative format, and (e) narrative as a form of action. Together, the themes
reveal that the story had utility, the various attributes that help explain why
this is case, how the utility might be maximized, what the stories could do on
and for people, and how the narratives can be used to support behavior change.
CONCLUSIONS: The article advances knowledge by revealing the value of narrative
as a means for disseminating evidence-based information to people with SCI and to
HCPs. It also reveals that stories can be used to facilitate dialogue, teach,
remind, reassure, and reinvigorate people. This article is a resource for
enabling knowledge to be more effectively shared to different audiences and
applying what we know in practice to help people live meaningful lives.
PMID- 25133830
TI - Stressful life events, sexual orientation, and cardiometabolic risk among young
adults in the United States.
AB - OBJECTIVE: The goal of the present study was to examine whether sexual minority
young adults are more vulnerable to developing cardiometabolic risk following
exposure to stressful life events than heterosexual young adults. METHOD: Data
came from the National Longitudinal Study for Adolescent Health (Shin, Edwards, &
Heeren, 2009; Brummett et al., 2013), a prospective nationally representative
study of U.S. adolescents followed into young adulthood. A total of 306 lesbian,
gay, and bisexual (LGB) respondents and 6,667 heterosexual respondents met
inclusion criteria for this analysis. Measures of cumulative stressful life
events were drawn from all 4 waves of data collection; sexual orientation and
cardiometabolic biomarkers were assessed at Wave 4 (2008-2009). RESULTS:
Gay/bisexual men exposed to 1-2 (beta = 0.71, p = .01) and 5+ (beta = 0.87, p =
.01) stressful life events had a statistically significant elevation in
cardiometabolic risk, controlling for demographics, health behaviors, and
socioeconomic status. Moreover, in models adjusted for all covariates,
lesbian/bisexual (beta = 0.52, p = .046) women with 5+ stressful life events had
a statistically significant elevation in cardiometabolic risk. There was no
relationship between stressful life events and cardiometabolic risk among
heterosexual men or women. CONCLUSION: Stressful life events during childhood,
adolescence, and young adulthood place LGB young adults at heightened risk for
elevated cardiometabolic risk as early as young adulthood. The mechanisms
underlying this relationship require future study.
PMID- 25133829
TI - Cognitive control in preadolescent children with risk factors for metabolic
syndrome.
AB - OBJECTIVE: To investigate the relationship between cognitive control and
metabolic syndrome (MetS) risk factors in preadolescent children while
controlling for aerobic fitness and weight status. METHODS: Hierarchical
regression analyses were conducted using aerobic fitness, demographic, and MetS
risk-factor variables in a sample of 2nd- and 3rd-grade children (n = 139) who
performed a modified version of a flanker task to assess cognitive control.
Flanker performance was also compared between children that met no MetS risk
factor criteria (n = 70), and children who met 1 criterion or more (n = 69).
RESULTS: Regression analyses indicated that after controlling for demographic
variables and fitness, HDL cholesterol exhibited an independent negative
association with flanker reaction time (RT). Group comparisons further revealed
that children with no risk factors demonstrated overall shorter RT than the at
risk group. In addition, at-risk children exhibited larger accuracy-interference
scores (i.e., poorer performance) for the more difficult conditions of the
flanker task that required the up-regulation of cognitive control to meet
elevated task demands. CONCLUSIONS: These findings are consonant with the
previous literature reporting a beneficial influence of aerobic fitness on
cognitive control, and reveal new evidence that children without risk factors for
MetS exhibit better inhibitory control and increased cognitive flexibility than
do at-risk children. In addition to aerobic fitness, these risk factors may serve
as important biomarkers for understanding the potential cognitive implications of
MetS risk in younger generations.
PMID- 25133832
TI - Are patient and relationship variables associated with participation of intimate
partners in couples research?
AB - BACKGROUND: Recruitment of participants for studies focusing on couples facing
illness is a challenging task and participation decline may be associated with
nonrandom factors creating bias. This study examines whether patient and
relationship characteristics are associated with partner participation in
research. METHOD: Patients invited to participate in a cross-sectional study on
adaptation and quality of life after renal transplantation were asked to forward
information about an add-on study to their partners. RESULTS: A total of 456
participating patients had a partner; 293 of the partners showed interest in the
study and 206 actually completed the questionnaire. Backward logistic regression
analyses revealed that demographic, illness, and personal characteristics of the
patient were not associated with partner interest in the study nor actual partner
participation. However, partners who indicated interest in the study showed more
active engagement toward the patients (as reported by the patients). Furthermore,
patients of partners who actually completed the questionnaire reported less
negative affect and higher relationship satisfaction than patients whose partner
did not participate in the study. DISCUSSION: It is encouraging that of the large
number of variables tested, only 2 were associated with the participation of
partners. Nevertheless, well-functioning couples appear to be overrepresented in
our study, calling for specific effort to include marital distressed couples in
research focusing on dyadic adaptation to illness.
PMID- 25133833
TI - The myth of comfort food.
AB - OBJECTIVE: People seek out their own idiosyncratic comfort foods when in negative
moods, and they believe that these foods rapidly improve their mood. The purpose
of these studies is to investigate whether comfort foods actually provide
psychological benefits, and if so, whether they improve mood better than
comparison foods or no food. METHODS: Participants first completed an online
questionnaire to indicate their comfort foods and a variety of comparison foods.
During two lab sessions a week apart from each other (and at least a week after
the online questionnaire, counterbalanced in order), participants watched films
that induced negative affect. In one session, participants were then served their
comfort food. In the other, participants were served an equally liked noncomfort
food (Study 1), a neutral food (Study 2), or no food (Studies 3 and 4). Short
term mood changes were measured so that we could seek out psychological effects
of these foods, rather than biochemical effects on mood from particular food
components (e.g., sugars or vitamins). RESULTS: Comfort foods led to significant
improvements in mood, but no more than other foods or no food. CONCLUSIONS:
Although people believe that comfort foods provide them with mood benefits,
comfort foods do not provide comfort beyond that of other foods (or no food).
These results are likely not due to a floor effect because participants' moods
did not return to baseline levels. Individuals may be giving comfort food
"credit" for mood effects that would have occurred even in the absence of the
comfort food.
PMID- 25133834
TI - Implicit prototypes predict risky sun behavior.
AB - OBJECTIVE: Despite the fact that skin cancer is highly avoidable, incidence and
death rates in the United States continue to climb. The pattern is particularly
problematic among young, White women, who sometimes overexpose themselves to
harmful ultraviolet rays in hopes of being tan. Research has suggested that
positivity toward prototypes of individuals who engage in unhealthy behavior,
like tanning, influences the likelihood that an individual will personally engage
in those behaviors. Although the prototype-to-behavior link is considered to
operate automatically, researchers have typically relied on people's self
reported evaluations of prototypes, which are more controlled and susceptible to
self-presentational concerns. METHOD: In the present research, we developed a
measure of implicit prototypes and compared it with measures of explicit
prototypes in predicting the safe sun behavior of 731 women. RESULTS: Meta
analysis of 5 different prototypes (i.e., cool, fun, healthy, intelligent, and
attractive) suggested that implicit prototypes predicted more variance in women's
current behavior, planned behavior, behavioral willingness, and tanning frequency
than did explicit prototypes. CONCLUSION: Although some models recognize that
health behavior may be based on automatic processes, they exclusively use
measures of self-reported attitudes and prototypes to predict behavior. The
results suggest that measuring implicit prototypes may provide important
explanatory power.
PMID- 25133835
TI - The question-behavior effect: genuine effect or spurious phenomenon? A systematic
review of randomized controlled trials with meta-analyses.
AB - OBJECTIVE: Simply answering questions about a specific behavior may change that
behavior. This is known as the mere-measurement or question-behavior effect
(QBE). Our objective was to synthesize the evidence for the QBE on health-related
behaviors. METHOD: Included studies were randomized controlled trials that tested
the effect of questionnaires or interviews about health-related behaviors and/or
related cognitions compared with a no-measurement control condition or another
form of measurement. Subgroup analyses were conducted to identify potential
moderators. RESULTS: 41 studies were included assessing a range of health
behaviors. Meta-analyses showed a small overall QBE effect (SMD = 0.09; 95% CI
[0.04, 0.13]; k = 33). Studies showed moderate heterogeneity, variable risk of
bias, and evidence of publication bias. No dose-response relationships were found
from studies comparing more with less intensive measurement conditions. There
were no significant differences in QBE by behavior, but QBEs for dental flossing,
physical activity, and screening attendance were significantly different from 0.
Findings were not altered by whether behavior or cognitions were measured,
attitudes were or were not measured, studies used questionnaires or interviews,
or outcomes were objective or self-reported. CONCLUSIONS: There is some evidence
for the QBE on health-related behavior. However, risk of bias within studies and
evidence of publication bias indicate that the observed small effect size may be
overestimated, especially given that some studies included intervention
techniques in addition to providing questionnaires. Preregistered high-quality
trials with clear specification of intervention content are needed to confirm if
and when measurement leads to behavior change.
PMID- 25133836
TI - Anger, provider responses, and pain: prospective analysis of stem cell transplant
patients.
AB - OBJECTIVE: Patient anger can be challenging for providers, and may hinder the
patient-provider relationship. Research on the relationships among patient anger,
relationships with health care providers and medical outcomes, however, has been
limited to anecdotal accounts and cross-sectional studies. This study examined
relationships among patient anger, perceptions of provider positive support and
negative interactions, by prospectively studying a sample of stem cell transplant
(SCT) patients. METHOD: A prospective design was used to study patient anger,
perceived positive support from providers and perceived negative interactions
with providers among 88 SCT patients. Data were obtained upon patient's
hospitalization before SCT and at 1, 2, and 3 month follow up periods. Repeated
measures mixed models assessed relationships among study variables. RESULTS:
Patient anger was associated with a gradual decline in perceived positive support
and higher levels of concurrent perceived negative interactions with providers.
Further, a significant lagged relationship was found such that patient anger was
associated with increased perceived negative interactions with providers 1 month
later. Exploratory analyses revealed that perceived negative interactions were
also associated with higher levels of physical distress. Perceived positive
support buffered the relationship between patient anger and physical distress,
such that anger was not associated significantly with physical distress when
perceived provider support was high. CONCLUSIONS: Patient anger may contribute to
a deterioration of the patient-provider relationship, and contribute to negative
medical outcomes including physical distress. The association between patient
anger and physical distress may be reduced by supportive providers.
PMID- 25133837
TI - Weight stigma mediates the association between BMI and self-reported health.
AB - OBJECTIVE: Weight stigma is pervasive in the United States. We tested the
hypothesis that stigma may be a mechanism through which obesity negatively
affects self-reported health. Two studies examined whether perceived weight-based
discrimination and concerns over weight stigma mediated the association between
BMI and self-reported psychological health (Study 1) and physical health (Study
2). METHOD: In 2 online studies, adult community members completed measures of
stigma-relevant mediators (perceived weight discrimination, weight stigma
concerns) and provided their height and weight. In Study 1 (N = 171) participants
also completed measures of psychological health (depression, self-esteem, quality
of life), whereas participants in Study 2 (N = 194) also completed a measure of
self-reported physical health. Process modeling was used to simultaneously test
for mediation through perceived discrimination and stigma concerns independently
as well as for serial mediation through both variables. RESULTS: Across both
studies, we hypothesized and found support for serial mediation such that BMI was
indirectly related to poorer self-reported health through its effect on perceived
discrimination and concerns about stigma. Additionally, concerns about stigma
mediated the association between BMI and health independent of perceived
discrimination. CONCLUSIONS: Weight stigma is an important mediator of the
association between BMI and self-reported health. Furthermore, results indicate
that concerns about facing stigma in the future mediate the link between
perceived past experiences of discrimination and psychological and physical
health.
PMID- 25133838
TI - Longitudinal association between child stress and lifestyle.
AB - OBJECTIVE: Psychosocial stress has been linked with an unhealthy lifestyle but
the relation's direction remains unclear. Does stress induce sleeping problems,
comfort food consumption, and lower physical activity, or do these unhealthy
lifestyle factors enhance stress? This study examined the bidirectional stress
lifestyle relation in children. METHOD: The relation between stress and lifestyle
was examined over 2 years in 312 Belgian children 5-12 years old as part of the
Children's Body Composition and Stress study. Stress-related aspects were
measured by questionnaires concerning negative events, negative emotions, and
behavioral problems. The following lifestyle factors were assessed: physical
activity (by accelerometers), sleep duration, food consumption (sweet food, fatty
food, snacks, fruits and vegetables), and eating behavior (emotional, external,
restrained). Bidirectional relations were examined with cross-lagged analyses.
RESULTS: Certain stress aspects increased physical activity, sweet food
consumption, emotional eating, restrained eating, and external eating (betas =
.140-.319). All relations were moderated by sex and age: Dietary effects were
mainly in the oldest children and girls; stress increased physical activity in
the youngest, whereas it tended to decrease physical activity in the oldest. One
reversed direction effect was found: Maladaptive eating behaviors increased
anxiety feelings. CONCLUSIONS: Relations were mainly unidirectional: Stress
influenced children's lifestyle. Stress stimulated eating in the absence of
hunger, which could facilitate overweight. Consequently, families should realize
that stress may influence children's diet, and problem-solving coping skills
should be acquired. In contrast to recent findings, stress might also stimulate
physical activity in the youngest as positive stress coping style.
PMID- 25133839
TI - Psychosocial, health-promotion, and neurocognitive interventions for survivors of
childhood cancer: a systematic review.
AB - OBJECTIVE: Survivors of childhood cancer must contend with a number of medical
and psychosocial vulnerabilities after their cancer treatment ends. Interventions
have been developed to alleviate or prevent adverse outcomes among this
population. This systematic review summarizes the efficacy of psychosocial,
health behavior, and neurocognitive interventions for survivors of pediatric
cancer. METHOD: Multiple databases were searched for studies published between
January 1970 and June 2013. Studies were coded by 2 raters for methodological
quality using the Effective Public Health Practice Project quality assessment
tool. RESULTS: Twenty-four interventions were identified (7 psychosocial, 10
health behavior, and 7 neurocognitive). Eleven were controlled trials, of which 7
achieved medium to large effect sizes. Survivor interest, as demonstrated by
consent rates, was high for interventions that did not require travel.
CONCLUSIONS: Interventions using delivery methods varying from traditional
counseling to computers achieved moderate to strong efficacy and merit
replication. Survivor needs related to transition to adult-oriented health care
and school reentry were not addressed by existing interventions. This review also
revealed the absence of health behavior interventions for survivors in middle
childhood and late adolescence. Intervention formats that are cost-effective and
reduce participant burden should be prioritized for further testing. To broaden
the reach and appeal of interventions, alternative delivery methods, such as
mobile phone software applications, should be evaluated.
PMID- 25133840
TI - Reflective and impulsive processes explain (in)effectiveness of messages
promoting physical activity: a randomized controlled trial.
AB - OBJECTIVE: The present study tested whether taking into account both the
reflective and the impulsive processes of physical activity (PA) is helpful in
understanding how, and for whom, PA-promoting messages will be (in)effective in
changing behavior. METHOD: Participants (N = 101) were presented with a
persuasive message promoting either PA (experimental condition) or healthy eating
(control condition). Reflective intentions to be physically active were assessed
both at baseline and after exposure to the message. Impulsive approach tendencies
toward PA (IAPA) and sedentary behaviors (IASB) were assessed using a manikin
task. The main outcome variable was accelerometer-assessed free time spent in
moderate to vigorous physical activity (MVPA) over 1 week after exposure to the
message. RESULTS: Although the PA-promoting message had no direct effect on MVPA,
the results showed that (a) this message increased intentions to practice PA,
notably among participants with low or moderate (but not high) baseline
intentions; (b) objective MVPA was positively predicted by postmessage PA
intentions and IAPA, and negatively predicted by IASB; and (c) postmessage PA
intentions predicted MVPA for individuals with low or moderate (but not high)
IASB. A follow-up moderated mediation analysis corroborated these earlier
results, showing that PA-promoting messages positively predicted MVPA through
postmessage intentions only among individuals with low or moderate baseline
intentions and low or moderate IASB. CONCLUSIONS: By identifying 2 boundary
conditions, this study revealed important insights in explaining when PA
promoting messages will be effective to predict objective MVPA and when they will
not.
PMID- 25133841
TI - Five-factor personality traits and sleep: evidence from two population-based
cohort studies.
AB - OBJECTIVE: The current study examines associations between five factor
personality traits and average sleep duration, sleep deficiency, and sleep
problems. METHOD: The participants were from two population-based samples from
Australia (n = 1,104, age range 31-41) and Finland (n = 1,623, age range 30-45).
Self-reports of sleep behavior, sleep problems (Jenkin's scale), and five factor
model personality traits (NEO-FFI) were collected. Associations between
personality traits and sleep were analyzed with linear regressions. RESULTS: The
results showed that higher extraversion, agreeableness, and conscientiousness
were, in general, associated with better sleep, whereas higher neuroticism was
associated with sleeping less well. Openness was not associated with sleep. Most
of the associations were replicable between the samples from the two countries,
but personality traits explained only small part of the variance in sleep
behavior. CONCLUSIONS: Increasing the knowledge on personality and sleep may
benefit more personalized treatment of sleep disorders and help in personnel
selection to jobs in which it is critical to stay alert. However, longitudinal
research is needed to confirm the current findings.
PMID- 25133842
TI - How do general practitioners and patients make decisions about cardiovascular
disease risk?
AB - OBJECTIVE: Although current guidelines around the world recommend using absolute
risk (AR) thresholds to decide whether cardiovascular disease (CVD) risk should
be managed with lifestyle or medication, the use of AR in clinical practice is
limited. The aim of this study was to explore the factors that influence general
practitioner (GP) and patient decision making about CVD risk management,
including the role of risk perception. METHODS: Qualitative descriptive study
involving semi-structured interviews with 25 GPs and 38 patients in Australia in
2011-2012. Transcribed audio-recordings were thematically coded and a Framework
Analysis method was used. RESULTS: GPs rarely mentioned AR thresholds but were
influenced by their subjective perception of the patient's risk and motivation,
and their own attitudes toward prevention, including concerns about medication
side effects and the efficacy of lifestyle change. Patients were influenced by
individual risk factors, their own motivation to change lifestyle, and attitudes
toward medication: initially negative, but this improved if medication was more
effective than lifestyle. High perceived risk led to medication being recommended
by GPs and accepted by patients, but this was not necessarily based on AR.
Patient perceptions of high risk also increased motivation to change lifestyle,
particularly if they were resistant to the idea of taking medication.
CONCLUSIONS: Perceived risk, motivation, and attitudes appeared to be more
important than AR thresholds in this study. CVD risk management guidelines could
be more useful if they include strategies to help GPs consider patients' risk
perception, motivation, and attitudes as well as evidence-based recommendations.
PMID- 25133843
TI - A social rank explanation of how money influences health.
AB - OBJECTIVE: Financial resources are a potent determinant of health, yet it remains
unclear why this is the case. We aimed to identify whether the frequently
observed association between absolute levels of monetary resources and health may
occur because money acts an indirect proxy for a person's social rank. METHOD: To
address this question we examined over 230,000 observations on 40,400 adults
drawn from two representative national panel studies; the British Household Panel
Survey and the English Longitudinal Study of Ageing. We identified each person's
absolute income/wealth and their objective ranked position of income/wealth
within a social reference-group. Absolute and rank income/wealth variables were
then used to predict a series of self-reported and objectively recorded health
outcomes in cross-sectional and longitudinal analyses. RESULTS: As anticipated,
those with higher levels of absolute income/wealth were found to have better
health than others, after adjustment for age, gender, education, marital status,
and labor force status. When evaluated simultaneously the ranked position of
income/wealth but not absolute income/wealth predicted all health outcomes
examined including: objective measures of allostatic load and obesity, the
presence of long-standing illness, and ratings of health, physical functioning,
role limitations, and pain. The health benefits of high rank were consistent in
cross-sectional and longitudinal analyses and did not depend on the reference
group used to rank participants. CONCLUSIONS: This is the first study to
demonstrate that social position rather than material conditions may explain the
impact of money on human health.
PMID- 25133845
TI - The relationship between the belief in a genetic cause for breast cancer and
bilateral mastectomy.
AB - OBJECTIVE: Most women develop causal beliefs following diagnosis with breast
cancer and these beliefs can guide decisions around their care and management.
Bilateral mastectomy rates are increasing, although the benefits of this surgery
are only established in a small percentage of women. In this study we
investigated the relationship between causal beliefs and the decision to have a
bilateral mastectomy. METHOD: Women (N = 2,269) from the Army of Women's breast
cancer research registry completed an online survey. Women were asked what they
believed caused their cancer and responses were coded into 8 causal categories.
Participants were also asked about the type of surgery they underwent following
their breast cancer diagnosis. The odds ratios for having a double mastectomy
were calculated for each causal category using random/bad luck as a referent
category. RESULTS: Hormonal factors (22%) and genetics (19%) were the most common
causal belief, followed by don't know (19%), environmental toxins (11%), negative
emotions (9%), poor health behavior (8%), other (6%) and random/bad luck (6%).
Compared with the referent category, the odds ratio of having a bilateral
mastectomy was significantly higher in both the genetics and hormonal causal
belief groups (OR = 2.36, 95% CI [1.38, 4.02] and OR = 1.98, 95% CI [1.16, 3.38],
respectively). CONCLUSIONS: Beliefs in a genetic cause for breast cancer are
common and are associated with high rates of bilateral mastectomy. This is
despite evidence that the actual genetic contribution to breast cancer is much
lower than perceived and that bilateral mastectomy is, in most cases, unlikely to
improve survival. (PsycINFO Database Record
PMID- 25133844
TI - Variations in sleep characteristics and sleep-related impairment in at-risk
college drinkers: a latent profile analysis.
AB - OBJECTIVE: Sleep disturbance and heavy drinking increase risk of negative
consequences in college students. Limited research exists on how they act
synergistically, and the overall nature of sleep and sleep-related impairment in
college student drinkers is poorly understood. A latent profile analysis was
conducted on the sleep characteristics and daytime sleep-related consequences of
college student drinkers who were at-risk based on Alcohol Use Disorders
Identification Test-Consumption scores. METHODS: Participants (N = 312, mean age
= 18.90 (0.97) years) consumed a mean (SD) of 20.93 (13.04) drinks per week.
Scores on the 10 items of the Sleep/Wake Behavior Problems Scale (SWPS) were the
class indicators. RESULTS: Four classes best described the sleep and sleep
related consequences of at-risk college drinkers. Classes represented different
gradients and types of sleep patterns and sleep-related impairment; nearly half
the sample reported late bedtimes and daytime consequences of insufficient sleep.
Subsequent validation analyses indicated that these classes were directly
correspondent with severity of alcohol consumption, alcohol-related consequences
illicit substance use, and perceived health. CONCLUSIONS: These findings indicate
the presence of significant heterogeneity in college drinkers' sleep patterns and
experiences of sleep-related impairment. Class differences significantly impact
the level of alcohol and drug use and the consequences members experience.
Greater alcohol use and sleep/wake problems are associated with increased risk
for negative consequences for certain classes. These results suggest that college
drinking interventions could benefit from the incorporation of sleep-related
content and the value in adding brief alcohol assessments and interventions to
other college health treatments.
PMID- 25133846
TI - The impact of self-affirmation on health-behavior change: a meta-analysis.
AB - OBJECTIVES: Self-affirmation (induced by reflecting upon important values,
attributes, or social relations) appears to reduce defensive resistance to health
risk information and increase subsequent readiness for health behavior change.
However, these effects of self-affirmation have yet to be subjected to formal,
quantitative integration. Consequently, the current article reports a meta
analysis of the impact of self-affirmation on outcomes at 3 key points in the
process of health-behavior change: (a) message acceptance, (b) intentions to
change, and (c) subsequent behavior. METHOD: The literature search identified 144
experimental tests of the effects of manipulating self-affirmation on these
outcomes. Effect sizes were extracted and meta-analyzed. RESULTS: Across 34 tests
of message acceptance (N = 3,433), 64 tests of intentions (N = 5,564), and 46
tests of behavior (N = 2,715), random effects models indicated small but reliable
positive effects of self-affirmation on each outcome: acceptance, d+ = .17(CI =
.03 to .31); intentions, d+ = .14 (CI = .05 to .23); behavior, d+ = .32 (CI = .19
to .44). Findings held across a range of health problems and behaviors.
CONCLUSIONS: The results suggest that deploying self-affirmation inductions
alongside persuasive health information has positive effects, promoting message
acceptance, intentions to change, and subsequent behavior. Though the effects are
small in magnitude, they are comparable to those obtained in meta-analyses of
other health-behavior change interventions. These findings are relevant to
researchers and practitioners working to understand why people resist beneficial
health information and how such resistance can be reduced.
PMID- 25133847
TI - Tricksterdom in narratives of young adult cancer: performances of uncertainty,
subversion, and possibility.
AB - OBJECTIVE: As people with cancer attempt the difficult task of giving voice to
life with illness, they often turn to mythic figures and stories (e.g., when
people talk about battling cancer or embarking on a journey toward recovery).
Little attention has been paid to the mythic figure of the trickster, recently
identified by Arthur Frank (2009) as a prominent trope in some narrative accounts
of illness. We investigated the prevalence of 3 tricksterly themes expressed
within young adults' stories of cancer: destabilizing social or cosmic order
(uncertainty), challenging dominant expectations for human life (subversion), and
exploring alternative ways of viewing the world (possibility). METHOD: We
recruited 21 young adults with cancer from across Canada and conducted
semistructured interviews. We then analyzed their stories using some elements of
thematic, structural, and dialogical/performative narrative analysis-drawing
attention to what was told and how/to whom were they told (Crossley, 2000; Frank,
2012; Riessman, 2008). RESULTS: We describe each of the 3 themes in turn (i.e.,
uncertainty, subversion, and possibility) using excerpts from 6 interview
transcripts, and show how they meaningfully converge into an interpretive
framework of tricksterdom. CONCLUSION: We conclude that the 3 themes of
uncertainty, subversion, and possibility seem to come together as tricksterly
performances, disrupting audiences' expectations of more typical forms of cancer
narratives and calling attention to less familiar, structured, and "tellable"
ways of narrating illness.
PMID- 25133848
TI - The roles of self-efficacy and motivation in the prediction of short- and long
term adherence to exercise among patients with coronary heart disease.
AB - OBJECTIVES: Poor adherence to regular exercise is a documented challenge among
people with heart disease. Identifying key determinants of exercise adherence and
distinguishing between the processes driving short- and long-term adherence to
regular exercise is a valuable endeavor. The purpose of the present study was to
test a model of exercise behavior change, which incorporates motivational
orientations and self-efficacy for exercise behavior, in the prediction of short-
and long-term exercise adherence. METHOD: Male and female patients (N = 801)
hospitalized for coronary heart disease were recruited from 3 tertiary care
cardiac centers and followed for a period of 1 year after hospital discharge. A
prospective, longitudinal design was used to examine the roles of motivation and
self-efficacy (measured at recruitment and at 2 and 6 months after discharge) in
the prediction of exercise behavior at 6 and 12 months. Baseline measures of
exercise and clinical and demographic covariates were included in the analyses.
RESULTS: Structural equation modeling showed that both autonomous motivation and
self-efficacy were important determinants of short-term (6-month) exercise
behavior regulation, but that only autonomous motivation remained a significant
predictor of long-term (12-month) exercise behavior. Self-efficacy partially
mediated the relationship between motivation for exercise and 6-month exercise
behavior. CONCLUSIONS: This research confirmed the roles of autonomous motivation
and self-efficacy in the health behavior change process and emphasized the key
function of autonomous motivation in exercise maintenance. Theoretical and
cardiac rehabilitation program applications of this research are discussed.
PMID- 25133849
TI - Synthesis of benzobicycloheptanones via the trap of photogenerated ketene methide
intermediate with olefins.
AB - Irradiation of ortho-formyl dienes with UV light led to benzobicycloheptanones in
high yields and chemoselectivities via a photogenerated ketene methide/Diels
Alder cascade reaction. The reaction mechanism was proposed to be a [1,5]-H shift
process rather than a radical pathway based on control experiments. DFT
calculations indicate that the energy of transition states is responsible for the
high chemoselectivity observed in this protocol.
PMID- 25133850
TI - Bioavailability and biological effect of engineered silver nanoparticles in a
forest soil.
AB - The extensive use of silver nanoparticles (SNPs) as antimicrobial in food,
clothing and medicine, leads inevitably to a loss of such nanomaterial in soil
and water. Little is known about the effects of soil contamination, in
particular, on microbial cells, which play a fundamental ecological role. In this
work, the impact of SNPs on forest soil has been studied, investigating eco
physiological indicators of microbial biomass and microbial diversity with
culture-dependent and independent techniques. Moreover, SNPs bioavailability and
uptake were assessed. Soil samples were spiked with SNPs at two different
concentrations (10 and 100 MUg g(-1)dw) and incubated with the relative controls
for 30, 60 and 90 days. The overall parameters showed a significant influence of
the SNPs on the soil microbial community, revealing a marked shift after 60 days
of incubation.
PMID- 25133851
TI - Influence of residual polymer on nanoparticle deposition in porous media.
AB - Although surface coatings and free polymers are known to affect the mobility of
nanoparticles in water-saturated porous media, the influence of these compounds
on nanoparticle deposition behavior has received limited attention. A series of
column experiments was conducted to evaluate the transport and retention of
quantum dots (QDs) coated with a synthetic polymer, polyacrylic acid-octylamine
(PAA-OA). Initial column studies, conducted with three size fractions of Ottawa
sand, resulted in unusual solid-phase retention profiles, characterized by low QD
deposition near the column inlet and increasing solid-phase concentrations along
the column until a plateau or limiting capacity was reached near the column
midpoint. Mathematical modeling studies indicated that the observed retention
behavior could not be reproduced using one-dimensional simulators based on either
clean-bed filtration theory or a modified filtration theory (MFT) model that
incorporated a maximum retention capacity. Additional column studies demonstrated
that changes in the inlet end plate configuration designed to ensure uniform flow
did not alter the observed effluent breakthrough curves (BTCs) or shape of the
retention profile. Subsequent QD transport experiments, pretreated by flushing
with a pulse of PAA-OA solution, resulted in almost complete QD breakthrough with
minimal retention. It is postulated that free polymer was preferentially adsorbed
onto the solid surface near the column inlet, thereby preventing QD attachment,
whereas in the down-gradient portion of the column, QDs attached to the solid
phase without competition from the polymer. These findings reveal the importance
of accounting for the influence of coconstituents on nanoparticle deposition and
demonstrate the need to simulate both transport and retention data when assessing
nanoparticle mobility in porous media.
PMID- 25133852
TI - Malignancy risk stratification in thyroid nodules with nondiagnostic results at
cytologic examination: combination of thyroid imaging reporting and data system
and the Bethesda System.
AB - PURPOSE: To evaluate the malignancy risks of thyroid nodules with nondiagnostic
results at ultrasonography (US)-guided fine-needle aspiration biopsy ( FNAB fine
needle aspiration biopsy ) and the criteria for selecting those for repeat US
guided FNAB fine-needle aspiration biopsy according to the thyroid imaging
reporting and data system ( TIRADS thyroid imaging reporting and data system ).
MATERIALS AND METHODS: This retrospective study was approved by the institutional
review board, and the requirement to obtain informed consent was waived. Five
hundred forty-eight nondiagnostic nodules were included. US features of internal
composition, echogenicity, margin, calcifications, shape, and vascularity were
evaluated, and thyroid nodules were classified according to TIRADS thyroid
imaging reporting and data system . TIRADS thyroid imaging reporting and data
system category 3 included nodules without any suspicious features of solidity,
hypoechogenicity or marked hypoechogenicity, microlobulated or irregular margins,
microcalcifications, and taller-than-wide shape. Categories 4a, 4b, 4c, and 5
included nodules with one, two, three or four, or five suspicious US features.
The malignancy risk was calculated. RESULTS: Of the 548 nodules, 40 (7.3%) were
malignant and 508 (92.7%) were benign. The malignancy risks of categories 3 and
4a nodules were 0.8% and 1.8%, respectively, whereas the malignancy risks of
categories 4b, 4c, and 5 nodules were 6.1%, 14.4%, and 31%. In the 294 nodules
larger than 10 mm, the malignancy risks of categories 3, 4a, 4b, 4c, and 5
nodules were 0.9%, 1.3%, 0%, 15%, and 33%, respectively. In the 254 nodules
measuring 10 mm or smaller, the malignancy risks of categories 3, 4a 4b, 4c, and
5 nodules were 0%, 2.7%, 14%, 14.3%, and 31%. CONCLUSION: Nondiagnostic thyroid
nodules without suspicious US features and those with one suspicious feature can
be followed up with US, but nondiagnostic nodules with two or more suspicious
features should undergo repeat US-guided FNAB fine-needle aspiration biopsy.
PMID- 25133854
TI - Temperature-dependent wear mechanisms for magnetron-sputtered AlTiTaN hard
coatings.
AB - AlTiTaN coatings have been demonstrated to have high thermal stability at
temperatures up to 900 degrees C. It has been speculated that the high oxidation
resistance promotes an improved wear resistance, specifically for dry machining
applications. This work reports on the influence of temperature up to 900
degrees C on the wear mechanisms of AlTiTaN hard coatings. DC magnetron-sputtered
coatings were obtained from an Al(46)Ti(42)Ta(12) target, keeping the substrate
bias at -100 V and the substrate temperature at 265 degrees C. The coatings
exhibited a single-phase face-centered cubic AlTiTaN structure. The dry sliding
tests revealed predominant abrasion and tribo-oxidation as wear mechanisms,
depending on the wear debris formed. At room temperature, abrasion leading to
surface polishing was observed. At 700 and 800 degrees C, slow tribo-oxidation
and an amorphous oxide formed reduced the wear rate of the coating compared to
room temperature. Further, an increase in temperature to 900 degrees C increased
the wear rate significantly due to fast tribo-oxidation accompanied by grooving.
The friction coefficient was found to decrease with temperature increasing from
700 to 900 degrees C due to the formation of oxide scales, which reduce adhesion
of asperity contacts. A relationship between the oxidation and wear mechanisms
was established using X-ray diffraction, Raman spectroscopy, scanning electron
microscopy, surface profilometry, confocal microscopy, and dynamic secondary ion
mass spectrometry.
PMID- 25133855
TI - Therapist adherence in individual cognitive-behavioral therapy for binge-eating
disorder: assessment, course, and predictors.
AB - While cognitive-behavioral therapy (CBT) is the most well-established treatment
for binge-eating disorder (BED), little is known about process factors
influencing its outcome. The present study sought to explore the assessment of
therapist adherence, its course over treatment, and its associations with patient
and therapist characteristics, and the therapeutic alliance. In a prospective
multicenter randomized-controlled trial comparing CBT to internet-based guided
self-help (INTERBED-study), therapist adherence using the newly developed
Adherence Control Form (ACF) was determined by trained raters in randomly
selected 418 audio-taped CBT sessions of 89 patients (25% of all sessions).
Observer-rated therapeutic alliance, interview-based and self-reported patient
and therapist characteristics were assessed. Three-level multilevel modeling was
applied. The ACF showed adequate psychometric properties. Therapist adherence was
excellent. While significant between-therapist variability in therapist adherence
was found, within-therapist variability was non-significant. Patient and
therapist characteristics did not predict the therapist adherence. The therapist
adherence positively predicted the therapeutic alliance. The ACF demonstrated its
utility to assess therapist adherence in CBT for BED. The excellent levels of
therapist adherence point to the internal validity of the CBT within the INTERBED
study serving as a prerequisite for empirical comparisons between treatments.
Variability between therapists should be addressed in therapist trainings and
dissemination trials.
PMID- 25133856
TI - Short-term effectiveness of an online behavioral training in migraine self
management: a randomized controlled trial.
AB - Behavioral training (BT) is recommended as a supplementary preventive treatment
for migraine. Online interventions have been successful in promoting health
behavior change, the evidence for online BT in migraine is limited, however. This
randomized controlled trial aimed to determine the post-treatment effectiveness
of online BT (n = 195) compared to a waitlist control group (WLC; n = 173) on
migraine attack frequency (primary outcome), headache self-efficacy and locus of
control (secondary outcomes). BT aims to counteract attacks in the prodromal
stage through early detection of prodromal features and self-management via
physical relaxation and cognitive behavioral regulation, and was offered with
minimal e-mail support in eight online lessons. Results showed that 120 (62%)
participants completed BT. A decrease of 20-25% in migraine attack frequency was
found in both conditions without a between-group difference (ES = 0.02, p = .71).
BT participants improved more than WLC participants on migraine related self
efficacy (ES = 0.86, p < .001), developed more internal (ES = 0.57, p < .001),
and less external control (ES = 0.78, p < .001). To conclude, results at post
training did not corroborate that improvements in migraine attack frequency were
due to online BT, the waitlist control group improved accordingly. However,
positive effects of BT on self-efficacy and locus of control were established. We
have to await the long term effects to see if improvements in psychological
variables translate to a reduction in migraine headache.
PMID- 25133858
TI - Synthesis and optophysical properties of dimeric aza-BODIPY dyes with a push-pull
benzodipyrrolidone core.
AB - A series of benzodipyrrolidone-based dimeric aza-BODIPY dyes with a push-pull
structure are synthesized. Single crystal X-ray diffraction demonstrates these
extended aza-BODIPY dyes are planar. The resulting aza-BODIPY chromophores
exhibit intense absorption in the 450-800 nm regions and possess lower-lying LUMO
energy levels. Furthermore, the push-pull substituents on aza-BODIPYs core have a
positive effect on their optophysical properties.
PMID- 25133857
TI - Visual disability rates in a ten-year cohort of patients with anterior visual
pathway meningiomas.
AB - PURPOSE: To examine the visual outcome of anterior visual pathway meningioma
(AVPM) patients followed for at least one year. METHODS: Data were collected on
demographics, clinical course and management. Visual disability was classified at
the first and last examination as follows: I--no visual disability; II--mild
visual defect in one eye; III--mild visual defect in both eyes; IV--loss of
driver's license; V--legally blind. RESULTS: Eight-one AVPM patients had their
tumor originate in the clinoid process in 23 (28%), sphenoid-wing area in 18
(22%), cavernous sinus in 15 (19%), tuberculum sellae in 8 (10%), and mixed in 17
(21%). On last examination, 46 patients (57%) had good visual acuity in one or
both eyes (Class I or II) and 17 (21%) were mildly affected in both eyes. The
rate of Class IV disability was 16%, and Class V disability was 6%. CONCLUSIONS:
Attention needs to be addressed to the considerable proportion of patients with
AVPM (22% in this study) who may lose their driver's license or become legally
blind. Occupational therapists should play an important role in the
multidisciplinary management of those patients to help them adapt to their new
physical and social situation. IMPLICATIONS FOR REHABILITATION: Anterior visual
pathway meningiomas (AVPMs) are commonly not life-threatening but they can lead
to profound visual disability, especially when the tumor originates in the
tuberculum sellae and cavernous sinus. Particular attention should be paid to
visual acuity and visual field deficits, as these can profoundly affect the
patient's quality of life including ability to drive and activities of daily
living. The interdisciplinary management of patients with AVPM should include the
neurosurgeon, neuro-ophthalmologist and occupational therapist. Also, early
intervention by the occupational therapist can help patients adapt to their
current physical and social situation and return to everyday tasks more rapidly.
PMID- 25133859
TI - Highly efficient functional GexPb1-xTe based thermoelectric alloys.
AB - Methods for enhancement of the direct thermal to electrical energy conversion
efficiency, upon development of advanced thermoelectric materials, are constantly
investigated mainly for efficient implementation of thermoelectric devices in
automotive vehicles, for converting the waste heat generated in such engines into
useful electrical power and thereby reduction of the fuel consumption and CO2
emission levels. It was recently shown that GeTe based compounds and specifically
GeTe-PbTe rich alloys are efficient p-type thermoelectric compositions. In the
current research, Bi2Te3 doping and PbTe alloying effects in GexPb1-xTe alloys,
subjected to phase separation reactions, were investigated for identifying the
phase separation potential for enhancement of the thermoelectric properties
beyond a pure alloying effect. All of the investigated compositions exhibit
maximal dimensionless figure of merit, ZT, values beyond 1, with the
extraordinary value of 2.1 found for the 5% Bi2Te3 doped-Ge0.87Pb0.13Te
composition, considered as among the highest ever reported.
PMID- 25133860
TI - Walking Workstation Use Reduces Ambulatory Blood Pressure in Adults With
Prehypertension.
AB - BACKGROUND: The acute effect of low-intensity walking on blood pressure (BP) is
unclear. PURPOSE: To determine if the acute use of a walking workstation reduces
ambulatory blood pressure (ABP) in prehypertensive men and women. METHODS: Ten
prehypertensive adults participated in a randomized, cross-over study that
included a control workday and a walking workstation workday. ABP was measured
for 7 hour during the workday and for 6 hour after work. RESULTS: Both systolic
BP (SBP) (134 +/- 14 vs. 137 +/- 16 mmHg; P = .027) and diastolic BP (DBP) (79 +/
10 vs. 82 +/- 12 mmHg; P = .001) were lower on the walking workstation day.
Postwork hours (4:00 PM-10:00 PM), SBP (129 +/- 13 vs. 133 +/- 14 mmHg; P =
.008), and DBP (74 +/- 11 vs. 78 +/- 13 mmHg; P = .001) were also lower on the
walking workstation day. DBP load was significantly lower during the walking
workstation day, with only 14% of the readings above 90 mmHg compared with 22% of
the control day readings (P = .037). CONCLUSION: Accumulation of very-light
intensity physical activity (~2 METs) over the course of a single work day using
a walking workstation may reduce BP burden in prehypertensive individuals.
PMID- 25133861
TI - Automatic generic registration of mass spectrometry imaging data to histology
using nonlinear stochastic embedding.
AB - The combination of mass spectrometry imaging and histology has proven a powerful
approach for obtaining molecular signatures from specific cells/tissues of
interest, whether to identify biomolecular changes associated with specific
histopathological entities or to determine the amount of a drug in specific
organs/compartments. Currently there is no software that is able to explicitly
register mass spectrometry imaging data spanning different ionization techniques
or mass analyzers. Accordingly, the full capabilities of mass spectrometry
imaging are at present underexploited. Here we present a fully automated generic
approach for registering mass spectrometry imaging data to histology and
demonstrate its capabilities for multiple mass analyzers, multiple ionization
sources, and multiple tissue types.
PMID- 25133862
TI - Management of Hodgkin's lymphoma with midbrain involvement: A case report and
review of literature.
AB - Introduction Primary central nervous system (CNS) involvement of Hodgkin's
lymphoma is very uncommon. There are only a few previous reports of Hodgkin's
lymphoma of nodular lymphocyte predominant histology involving the CNS
concurrently with systemic disease. Case presentation A 12-year-old boy with a
history of painless left inguinal swelling and acute diplopia. There was an
intensely enhancing lesion in the right midbrain on magnetic resonance imaging.
The patient was diagnosed with stage IV Hodgkin's lymphoma of nodular lymphocyte
predominance type by routine microscopy and immunohistochemistry of left inguinal
lymph node biopsy with computed tomography-assisted staging. It was planned to
treat him with six cycles of chemotherapy with intrathecal methotrexate, followed
by radiotherapy to the CNS lesions. After two cycles of chemotherapy, the patient
entered complete remission of all lesions including the CNS lesion documented by
the positron emission tomography scan. Conclusion We are describing the course of
this rare presentation of Hodgkin's lymphoma of nodular lymphocyte predominant
histology involving the CNS and clinical challenge in its diagnosis and
management of this case.
PMID- 25133864
TI - High-temperature, high-pressure hydrothermal synthesis, characterization, and
structural relationships of layered uranyl arsenates.
AB - Five new uranyl arsenates, Na14[(UO2)5(AsO4)8].2H2O (1), K6[(UO2)5O5(AsO4)2]
(2a), K4[(UO2)3O2(AsO4)2] (2b), Rb4[(UO2)3O2(AsO4)2] (3), and
Cs6[(UO2)5O2(AsO4)4] (4), were synthesized by high-temperature, high-pressure
hydrothermal reactions at about 560 degrees C and 1440 bar and were
characterized by single-crystal X-ray diffraction, thermogravimetric analysis,
and photoluminescence spectroscopy. Crystal data for compound 1: triclinic, P1, a
= 7.0005(3) A, b = 12.1324(4) A, c = 13.7428(5) A, alpha = 64.175(2) degrees ,
beta = 89.092(2) degrees , gamma = 85.548(2) degrees , V = 1047.26(7) A(3), Z =
1, R1 = 0.0185; compound 2a: monoclinic, P21/c, a = 6.8615(3) A, b = 24.702(1) A,
c = 7.1269(3) A, beta = 98.749(2) degrees , V = 1193.89(9) A(3), Z = 2, R1 =
0.0225; compound 2b: monoclinic, P21/c, a = 6.7852(3) A, b = 17.3640(8) A, c =
7.1151(3) A, beta = 98.801(3) degrees , V = 828.42(6) A(3), Z = 2, R1 = 0.0269;
compound 3: monoclinic, P21/m, a = 6.9783(3) A, b = 17.4513(8) A, c = 7.0867(3)
A, beta = 90.808(3) degrees , V = 862.94(7) A(3), Z = 2, R1 = 0.0269; compound 4:
triclinic, P1, a = 7.7628(3) A, b = 9.3324(4) A, c = 11.9336(4) A, alpha =
75.611(2) degrees , beta = 73.136(2) degrees , gamma = 86.329(2) degrees , V =
801.37(5) A(3), Z = 1, R1 = 0.0336. The five compounds have layer structures
consisting of uranyl square, pentagonal, and hexagonal bipyramids as well as AsO4
tetrahedra. Compound 1 contains chains of discrete uranyl square and pentagonal
bipyramids, 2a contains three-polyhedron-wide ribbons of edge- and corner-sharing
uranyl square and pentagonal bipyramids, 2b and 3 contain dimers of edge-shairing
pentagonal bipyramids that share edges with hexagonal bipyramids to form chains,
and 4 contains one-polyhedron-wide zigzag chains of edge-sharing uranyl
polyhedra. The double sheet structure of 1 is new, but the chain topology has
been observed in an organically templated uranyl sulfate. Compound 2b is a new
geometrical isomer of the phosphuranylite group. The sheet anion topologies of 2a
and 4 can be obtained by splitting the beta-U3O8-type sheet into complex chains
and connecting the chains by arsenates.
PMID- 25133865
TI - Biopolymer-based structuring of liquid oil into soft solids and oleogels using
water-continuous emulsions as templates.
AB - Physical trapping of a hydrophobic liquid oil in a matrix of water-soluble
biopolymers was achieved using a facile two-step process by first formulating a
surfactant-free oil-in-water emulsion stabilized by biopolymers (a protein and a
polysaccharide) followed by complete removal of the water phase (by either high-
or low-temperature drying of the emulsion) resulting in structured solid systems
containing a high concentration of liquid oil (above 97 wt %). The microstructure
of these systems was revealed by confocal and cryo-scanning electron microscopy,
and the effect of biopolymer concentrations on the consistency of emulsions as
well as the dried product was evaluated using a combination of small-amplitude
oscillatory shear rheometry and large deformation fracture studies. The oleogel
prepared by shearing the dried product showed a high gel strength as well as a
certain degree of thixotropic recovery even at high temperatures. Moreover, the
reversibility of the process was demonstrated by shearing the dried product in
the presence of water to obtain reconstituted emulsions with rheological
properties comparable to those of the fresh emulsion.
PMID- 25133863
TI - Infection management and multidrug-resistant organisms in nursing home residents
with advanced dementia.
AB - IMPORTANCE: Infection management in advanced dementia has important implications
for (1) providing high-quality care to patients near the end of life and (2)
minimizing the public health threat posed by the emergence of multidrug-resistant
organisms (MDROs). DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of
362 residents with advanced dementia and their health care proxies in 35 Boston
area nursing homes for up to 12 months. MAIN OUTCOMES AND MEASURES: Data were
collected to characterize suspected infections, use of antimicrobial agents
(antimicrobials), clinician counseling of proxies about antimicrobials, proxy
preference for the goals of care, and colonization with MDROs (methicillin
resistant Staphylococcus aureus, vancomycin-resistant enterococci, and multidrug
resistant gram-negative bacteria). Main outcomes were (1) proportion of suspected
infections treated with antimicrobials that met minimum clinical criteria to
initiate antimicrobial treatment based on consensus guidelines and (2) cumulative
incidence of MDRO acquisition among noncolonized residents at baseline. RESULTS:
The cohort experienced 496 suspected infections; 72.4% were treated with
antimicrobials, most commonly quinolones (39.8%) and third- or fourth-generation
cephalosporins (20.6%). At baseline, 94.8% of proxies stated that comfort was the
primary goal of care, and 37.8% received counseling from clinicians about
antimicrobial use. Minimum clinical criteria supporting antimicrobial treatment
initiation were present for 44.0% of treated episodes and were more likely when
proxies were counseled about antimicrobial use (adjusted odds ratio, 1.42; 95%
CI, 1.08-1.86) and when the infection source was not the urinary tract
(referent). Among noncolonized residents at baseline, the cumulative incidence of
MDRO acquisition at 1 year was 48%. Acquisition was associated with exposure (>1
day) to quinolones (adjusted hazard ratio [AHR], 1.89; 95% CI, 1.28-2.81) and
third- or fourth-generation cephalosporins (AHR, 1.57; 95% CI, 1.04-2.40).
CONCLUSIONS AND RELEVANCE: Antimicrobials are prescribed for most suspected
infections in advanced dementia but often in the absence of minimum clinical
criteria to support their use. Colonization with MDROs is extensive in nursing
homes and is associated with exposure to quinolones and third- and fourth
generation cephalosporins. A more judicious approach to infection management may
reduce unnecessary treatment in these frail patients, who most often have comfort
as their primary goal of care, and the public health threat of MDRO emergence.
PMID- 25133866
TI - Examining the Relationship Between Physical Activity Intensity and Adiposity in
Young Women.
AB - BACKGROUND: The purpose of this study was to assess the relationship between
intensity of physical activity (PA) and body composition in 343 young women.
METHODS: Physical activity was objectively measured using accelerometers worn for
7 days in women 17 to 25 years. Body composition was assessed using the BOD POD.
RESULTS: Young women who spent less than 30 minutes a week performing vigorous PA
had significantly higher body fat percentages than women who performed more than
30 minutes of vigorous PA per week (F = 4.54, P = .0113). Young women who spent
less than 30 minutes per day in moderate to vigorous PA (MVPA) had significantly
higher body fat percentages than those who obtained more than 30 minutes per day
of MVPA (F = 7.47, P = .0066). Accumulating more than 90 minutes of MVPA per day
was associated with the lowest percent body fat. For every 10 minutes spent in
MVPA per day, the odds of having a body fat percentage above 32% decreased by 29%
(P = .0002). CONCLUSION: Vigorous PA and MVPA are associated with lower
adiposity. Young women should be encouraged to accumulate at least 30 minutes of
MVPA per day, however getting more than 90 minutes a day is predictive of even
lower levels of adiposity.
PMID- 25133869
TI - Nine hundred.
PMID- 25133868
TI - Cardiac rehabilitation use among veterans with ischemic heart disease.
PMID- 25133870
TI - Cognitive profiles of elder adult protective services clients living in squalor.
AB - The purpose of this study was to determine whether squalor-dwelling Adult
Protective Services (APS) clients were more cognitively impaired than non-squalor
dwelling APS clients referred for decision-making capacity assessments. The
authors performed a retrospective medical record review of neuropsychological and
demographic data gathered during decisional capacity assessments. Squalor
dwelling was defined by unsanitary living conditions that posed a danger to the
occupant's health or safety. Mean neuropsychological test scores were compared
between squalor-dwelling (n = 50) and non-squalor-dwelling (n = 180) subjects.
Squalor-dwelling clients were significantly younger than non-squalor-dwelling
clients. There were no distribution differences among gender, education, race, or
rural-dwelling status. Although both groups performed poorly on each
neuropsychological measure, squalor dwellers demonstrated better memory and
general cognitive performance. Cognition, depression, gender, race, education,
dementia diagnosis, and rural-dwelling status seem insufficient to explain
squalor-dwelling behaviors. Other biological and psychosocial variables should be
considered.
PMID- 25133872
TI - Fe-catalyzed direct dithioacetalization of aldehydes with 2-chloro-1,3-dithiane.
AB - Present methods to synthesize 1,3-dithiane molecules require either harsh
reaction conditions or highly specialized reagents. We have developed a catalytic
dithioacetalization process that directly gains access to the corresponding 1,3
dithianes using aldehydes and 2-chloro-1,3-dithiane in a highly efficient manner.
This methodology is beneficial due to mildness of the reaction conditions, and
the dithioacetaliation process results in good to excellent yields by using 15
mol % of an iron catalyst.
PMID- 25133871
TI - Association of serum interleukin 6 and C-reactive protein in childhood with
depression and psychosis in young adult life: a population-based longitudinal
study.
AB - IMPORTANCE: Longitudinal studies have linked the systemic inflammatory markers
interleukin 6 (IL-6) and C-reactive protein (CRP) with the risk of developing
heart disease and diabetes mellitus, which are common comorbidities for
depression and psychosis. Recent meta-analyses of cross-sectional studies have
reported increased serum levels of these inflammatory markers in depression,
first-episode psychosis, and acute psychotic relapse; however, the direction of
the association has been unclear. OBJECTIVE: To test the hypothesis that higher
serum levels of IL-6 and CRP in childhood would increase future risks for
depression and psychosis. DESIGN, SETTING, AND PARTICIPANTS: The Avon
Longitudinal Study of Parents and Children (ALSPAC)is a prospective general
population birth cohort study based in Avon County, England. We have studied a
subsample of approximately 4500 individuals from the cohort with data on
childhood IL-6 and CRP levels and later psychiatric assessments. MEASUREMENT OF
EXPOSURE: Levels of IL-6 and CRP were measured in nonfasting blood samples
obtained in participants at age 9 years. MAIN OUTCOMES AND MEASURES: Participants
were assessed at age 18 years. Depression was measured using the Clinical
Interview Schedule-Revised (CIS-R) and Mood and Feelings Questionnaire (MFQ),
thus allowing internal replication; psychotic experiences (PEs) and psychotic
disorder were measured by a semistructured interview. RESULTS: After adjusting
for sex, age, body mass index, ethnicity, social class, past psychological and
behavioral problems, and maternal postpartum depression, participants in the top
third of IL-6 values compared with the bottom third at age 9 years were more
likely to be depressed (CIS-R) at age 18 years (adjusted odds ratio [OR], 1.55;
95% CI, 1.13-2.14). Results using the MFQ were similar. Risks of PEs and of
psychotic disorder at age 18 years were also increased with higher IL-6 levels at
baseline (adjusted OR, 1.81; 95% CI, 1.01-3.28; and adjusted OR, 2.40; 95% CI,
0.88-6.22, respectively). Higher IL-6 levels in childhood were associated with
subsequent risks of depression and PEs in a dose-dependent manner. CONCLUSIONS
AND RELEVANCE: Higher levels of the systemic inflammatory marker IL-6 in
childhood are associated with an increased risk of developing depression and
psychosis in young adulthood. Inflammatory pathways may provide important new
intervention and prevention targets for these disorders. Inflammation might
explain the high comorbidity between heart disease, diabetes mellitus,
depression, and schizophrenia.
PMID- 25133873
TI - Distributed polarizability models for imidazolium-based ionic liquids.
AB - Quantum chemical calculations are used to derive distributed polarizability
models sufficiently accurate and compact to be used in classical molecular
dynamics simulations of imidazolium-based room temperature ionic liquids. Two
distributed polarizability models are fitted to reproduce the induction energy of
three imidazolium cations (1,3-dimethyl-, 1-ethyl-3-methyl-, and 1-butyl-3
methylimidazolium) and four anions (tetrafluoroborate, hexafluorophosphate,
nitrate, and thiocyanate) polarized by a point charge located successively on a
grid of surrounding points. The first model includes charge-flow polarizabilities
between first-neighbor atoms and isotropic dipolar polarizability on all atoms
(except H), while the second model includes anisotropic dipolar polarizabilities
on all atoms (except H). For the imidazolium cations, particular attention is
given to the transferability of the distributed polarizability sets. The
molecular polarizability and its anisotropy rebuilt by the distributed models are
found to be in good agreement with the exact ab initio values for the three
cations and 23 additional conformers of 1-ethyl-3-methyl-, 1-butyl-3-methyl-, 1
pentyl-3-methyl-, and 1-hexyl-3-methylimidazolium cations.
PMID- 25133875
TI - A jogged dislocation governed strengthening mechanism in nanotwinned metals.
AB - Atomistic simulations reveal a new and unique strengthening mechanism in
nanotwinned metals governed by the collective motion of multiple necklace-like
extended jogged dislocations. This mechanism prevails in a columnar-grained
nanotwinned metal subject to an external stress parallel to the twin planes,
provided the twin boundary spacing falls below a critical value. A theoretical
model based on the depinning of unit jogs on twin planes is proposed to determine
the flow stress associated with this deformation mechanism and is shown to be in
agreement with atomistic simulations.
PMID- 25133874
TI - Impaired cerebrovascular reactivity in multiple sclerosis.
AB - IMPORTANCE: Cerebrovascular reactivity (CVR) is an inherent indicator of the
dilatory capacity of cerebral arterioles for a vasomotor stimulus for maintaining
a spontaneous and instant increase of cerebral blood flow (CBF) in response to
neural activation. The integrity of this mechanism is essential to preserving
healthy neurovascular coupling; however, to our knowledge, no studies have
investigated whether there are CVR abnormalities in multiple sclerosis (MS).
OBJECTIVE: To use hypercapnic perfusion magnetic resonance imaging to assess CVR
impairment in patients with MS. DESIGN, SETTING, AND PARTICIPANTS: A total of 19
healthy volunteers and 19 patients with MS underwent perfusion magnetic resonance
imaging based on pseudocontinuous arterial spin labeling to measure CBF at
normocapnia (ie, breathing room air) and hypercapnia. The hypercapnia condition
is achieved by breathing 5% carbon dioxide gas mixture, which is a potent
vasodilator causing an increase of CBF. MAIN OUTCOMES AND MEASURES:
Cerebrovascular reactivity was calculated as the percent increase of normocapnic
to hypercapnic CBF normalized by the change in end-tidal carbon dioxide, which
was recorded during both conditions. Group analysis was performed for regional
and global CVR comparison between patients and controls. Regression analysis was
also performed between CVR values, lesion load, and brain atrophy measures in
patients with MS. RESULTS: A significant decrease of mean (SD) global gray matter
CVR was found in patients with MS (3.56 [0.81]) compared with healthy controls
(5.08 [1.56]; P = .001). Voxel-by-voxel analysis showed diffuse reduction of CVR
in multiple regions of patients with MS. There was a significant negative
correlation between gray matter CVR and lesion volume (R = 0.6, P = .004) and a
significant positive correlation between global gray matter CVR and gray matter
atrophy index (R = 0.5, P = .03). CONCLUSIONS AND RELEVANCE: Our quantitative
imaging findings suggest impairment in functional cerebrovascular
pathophysiology, by measuring a diffuse decrease in CVR, which may be the
underlying cause of neurodegeneration in MS.
PMID- 25133877
TI - Development of a rapid capture-cum-detection method for Escherichia coli O157
from apple juice comprising nano-immunomagnetic separation in tandem with surface
enhanced Raman scattering.
AB - A combined capture and detection method comprising of nano-immunomagnetic
separation (NIMS) and surface enhanced Raman spectroscopy (SERS) was developed to
detect Escherichia coli O157 from liquid media including apple juice. The capture
antibodies (cAbs) were immobilized on magnetite-gold (Fe3O4/Au) magnetic
nanoparticles (MNPs) which were used for separation and concentration of the E.
coli O157 cells from model liquid food matrix. The capture efficiency (CE) for E.
coli O157 using MNP was found to be approximately 84-94%. No cross reactivity was
observed with background non-target organisms. There was a significant difference
in the mean CE of bacteria captured by MNP and commercially sourced
immunomagnetic microbeads (p<0.05). For the detection of target pathogen, SERS
labels were prepared by conjugating gold nanoparticles with Raman reporter
molecules and the detector antibody (dAb). Au-Raman label-dAb was interacted with
gold coated MNP-cAb-E. coli O157 complex. The ability of this immunoassay to
detect E. coli O157 in apple juice was investigated. We have successfully applied
the synthesized Fe3O4/Au nanoclusters to E. coli O157 detection in apple juice
using the SERS method. The lowest detectable bacterial cell concentration in
apple juice was 10(2)CFU/mL with a total analysis time of less than an hour. This
method presents a convenient way of preconcentration, separation, and detection
of low levels of target pathogen from liquid food matrix.
PMID- 25133876
TI - Epithelial interleukin-25 is a key mediator in Th2-high, corticosteroid
responsive asthma.
AB - RATIONALE: Activation of type 2 cytokine pathways plays a central role in a large
subset of subjects with asthma. Th2-high and Th2-low asthma have distinct
clinical, pathologic, and molecular phenotypes and respond differently to
therapy. The factors that initiate type 2 responses in some subjects with asthma
are unknown. OBJECTIVES: To determine whether expression of epithelial cytokines
IL-25, IL-33, and thymic stromal lymphopoietin are associated with type 2
responses and predict response to inhaled corticosteroid (ICS) in asthma.
METHODS: We analyzed pulmonary function tests, blood, and bronchoscopic biopsies
from 21 healthy control subjects and 43 subjects with asthma. Subjects with
asthma underwent an 8-week treatment with inhaled budesonide. MEASUREMENTS AND
MAIN RESULTS: Epithelial expression of IL-25, but not IL-33 or thymic stromal
lymphopoietin, was increased in a subset of subjects with asthma. The IL-25-high
subset had greater airway hyperresponsiveness, more airway and blood eosinophils,
higher serum IgE, more subepithelial thickening, and higher expression of Th2
signature genes. ICS improved FEV1 and hyperresponsiveness in the IL-25-high but
not the IL-25-low subset. Plasma IL-25 levels correlated with epithelial IL-25
expression, airway eosinophilia, and beneficial responses to ICS treatment.
CONCLUSIONS: IL-25 measurements identify two subsets of subjects with distinct
asthma phenotypes and different responses to ICS. Because IL-25 has a major role
in triggering type 2 responses, bronchial epithelial IL-25 expression is likely a
key determinant of type 2 response activation in asthma. Plasma IL-25 level
reflects airway IL-25/type 2 response activation and may be useful for predicting
responses to asthma therapy.
PMID- 25133878
TI - The contribution of the Israeli trauma system to the survival of road traffic
casualties.
AB - BACKGROUND: According to the World Health Organization, over one million people
die annually from traffic crashes, in which over half are pedestrians, bicycle
riders and two-wheel motor vehicles. In Israel, during the last decade, mortality
from traffic crashes has decreased from 636 in 1998 to 288 in 2011. Professionals
attribute the decrease in mortality to enforcement, improved infrastructure and
roads and behavioral changes among road users, while no credit is given to the
trauma system. Trauma systems which care for severe and critical casualties
improve the injury outcomes and reduce mortality among road casualties. GOALS: 1)
To evaluate the contribution of the Israeli Health System, especially the trauma
system, on the reduction in mortality among traffic casualties. 2) To evaluate
the chance of survival among hospitalized traffic casualties, according to age,
gender, injury severity and type of road user. METHODS: A retrospective study
based on the National Trauma Registry, 1998-2011, including hospitalization data
from eight hospitals. OUTCOMES: During the study period, the Trauma Registry
included 262,947 hospitalized trauma patients, of which 25.3% were due to a road
accident. During the study period, a 25% reduction in traffic related mortality
was reported, from 3.6% in 1998 to 2.7% in 2011. Among severe and critical (ISS
16+) casualties the reduction in mortality rates was even more significant, 41%;
from 18.6% in 1998 to 11.0% in 2011. Among severe and critical pedestrian
injuries, a 44% decrease was reported (from 29.1% in 1998 to 16.2% in 2011) and a
65% reduction among bicycle injuries. During the study period, the risk of
mortality decreased by over 50% from 1998 to 2011 (OR 0.44 95% 0.33-0.59. In
addition, a simulation was conducted to determine the impact of the trauma system
on mortality of hospitalized road casualties. Presuming that the mortality rate
remained constant at 18.6% and without any improvement in the trauma system, in
2011 there would have been 182 in-hospital deaths compared to the actual 108
traffic related deaths. A 41% difference was noted between the actual number of
deaths and the expected number. CONCLUSIONS: This study clearly shows that
without any improvement in the health system, specifically the trauma system, the
number of traffic deaths would be considerably greater. Although the health
system has a significant contribution on reducing mortality, it does not receive
the appropriate acknowledgment or resources for its proportion in the fight
against traffic accidents.
PMID- 25133879
TI - A direct biocombinatorial strategy toward next generation, mussel-glue inspired
saltwater adhesives.
AB - Biological materials exhibit remarkable, purpose-adapted properties that provide
a source of inspiration for designing new materials to meet the requirements of
future applications. For instance, marine mussels are able to attach to a broad
spectrum of hard surfaces under hostile conditions. Controlling wet-adhesion of
synthetic macromolecules by analogue processes promises to strongly impact
materials sciences by offering advanced coatings, adhesives, and glues. The de
novo design of macromolecules to mimic complex aspects of mussel adhesion still
constitutes a challenge. Phage display allows material scientists to design
specifically interacting molecules with tailored affinity to material surfaces.
Here, we report on the integration of enzymatic processing steps into phage
display biopanning to expand the biocombinatorial procedure and enable the direct
selection of enzymatically activable peptide adhesion domains. Adsorption
isotherms and single molecule force spectroscopy show that those de novo peptides
mimic complex aspects of bioadhesion, such as enzymatic activation (by
tyrosinase), the switchability from weak to strong binders, and adsorption under
hostile saltwater conditions. Furthermore, peptide-poly(ethylene oxide)
conjugates are synthesized to generate protective coatings, which possess anti
fouling properties and suppress irreversible interactions with blood-plasma
protein cocktails. The extended phage display procedure provides a generic way to
non-natural peptide adhesion domains, which not only mimic nature but also
improve biological sequence sections extractable from mussel-glue proteins. The
de novo peptides manage to combine several tasks in a minimal 12-mer sequence and
thus pave the way to overcome major challenges of technical wet glues.
PMID- 25133880
TI - Tigers and snakes in neuro-ophthalmology.
PMID- 25133881
TI - Cerebrospinal fluid pressure in adults.
AB - BACKGROUND: Lumbar puncture (LP) is a widely-used investigative procedure. It
allows relatively non-invasive measurement of intracranial pressure (ICP) which
may have a significant impact on diagnosis and/or patient management. Over the
years there has been considerable discussion about various aspects of the
procedure, including what constitutes a normal opening pressure, what factors
might influence this, and how LP is best performed. EVIDENCE ACQUISITION: A
review of the literature was carried out by searching PubMed and Medline,
scanning relevant medical journals for recent publications, and carrying out
secondary referencing and contacting other clinicians, where appropriate.
RESULTS: The normal range of ICP measured by LP in adults in a typical clinical
setting should now be regarded as 6 to 25 cmH2O (95% confidence intervals), with
a population mean of about 18 cmH2O. There is, however, considerable variability:
some normal individuals have pressures of 30 cmH2O (or, occasionally, even
higher) meaning that pressure measurements must be interpreted in the clinical
context. CONCLUSIONS: This article aims to provide the practicing neuro
ophthalmologist with up-to-date information about the ways in which various
factors can influence pressure measurements obtained at LP.
PMID- 25133882
TI - Interpretation of lumbar puncture opening pressure measurements in children.
AB - BACKGROUND: Understanding the reference range of cerebrospinal fluid opening
pressure (CSFOP) in children is essential to the diagnosis of elevated
intracranial pressure. Recent studies have highlighted several clinical elements
that need to be considered when interpreting CSFOP measures. EVIDENCE
ACQUISITION: This review and recommendations are based on peer-reviewed
literature, primarily from the past decade, as well as the author's clinical and
research experience. RESULTS: CSFOP measures <=28 cm H2O can be considered
"normal" for most children. The patient's depth of sedation, body mass index, and
sedation medication can sometimes result in small increases in CSFOP. Patient age
and leg position (flexed vs extended) in the lateral decubitus position do not
seem to significantly impact CSFOP measures. CONCLUSIONS: The threshold of a
normal CSFOP should not be interpreted in isolation, but instead, in concert with
other clinical and examination findings to help the physician make a well
informed assessment of whether a child has elevated intracranial pressure.
PMID- 25133884
TI - A 16-year-old boy with a suprasellar mass.
PMID- 25133883
TI - Noninvasive assessment of cerebrospinal fluid pressure.
AB - Measurement of intracranial pressure (ICP) is critical for the evaluation and
management of many neurological and neurosurgical conditions. The invasiveness of
ICP measurement limits the frequency with which ICP can be evaluated, hampering
the clinical care of patients with ICP disorders. Thus, there has been
substantial interest in developing noninvasive methods for the assessment of ICP.
Numerous approaches have been applied to the problem, although none seems to
represent a complete solution. The goal of this review is to familiarize the
reader with the currently available methods to noninvasively evaluate ICP.
PMID- 25133885
TI - Do patients with neurologically isolated ocular motor cranial nerve palsies
require prompt neuroimaging?
PMID- 25133887
TI - The role of the American Academy of Family Physicians in supporting
breastfeeding.
PMID- 25133888
TI - Re: Marchington JM, Burd GP. Author attitudes to professional medical writing
support. Curr Med Res Opin 2014 Jul 9:1-6.
PMID- 25133890
TI - Metazoan symbionts of the yellow clam, Mesodesma donacium (Bivalvia), in southern
Chile: geographical variations.
AB - Mesodesma donacium is a dominant species on sandy beaches along the Chilean
coast. However, the only previous parasite records for this species were obtained
for the northern Chilean coast (20 degrees S-33 degrees S), which dealt with
cestodes, polychaetes, and copepods. In this study, the symbiotic fauna of M.
donacium in its southern distributional range is reported, and the geographical
variations in the occurrence of this fauna are evaluated. A total of 565
individuals of M. donacium were captured by local fishermen from 5 localities:
Mehuin (MEH) (39 degrees 26' S), Carelmapu (CAR) (41 degrees 44' S), Ancud
(ANC) (41 degrees 53' S), Cucao (CUC) (42 degrees 35' S), and Quellon (QUE) (43
degrees 24' S), covering a total distance of 450 km. To collect metazoan
symbionts, the valves, mantle, gills, gonad, and digestive gland of each specimen
of yellow clam were examined, and symbiont identifications were made via
morphological and genetic analyses. The prevalence and mean intensity of
infestation were calculated for each symbiotic species. Univariate and
multivariate analyses were performed to evaluate the differences in symbiotic
load between localities. Seven metazoan symbiotic species were recorded. The most
abundant species were Paranthessius mesodesmatis, Monorchiidae gen. sp., and
Paravortex sp. The copepod P. mesodesmatis and metacercaria Monorchiidae gen. sp.
showed a high prevalence in all localities, but their intensity of infection
varied among localities. The turbellarian Paravortex sp. was most frequently
associated with ANC and CUC. The digenean Sanguinicolidae gen. sp. was recorded
only at CAR, and the polychaete Spionidae gen. sp. was recorded only at MEH. In
its southern distributional range, M. donacium was characterized by an absence of
cestodes. This absence can be explained by the absence of the definitive host.
The local environmental conditions in the southern range of the host could
explain the differences in symbiotic composition among localities.
PMID- 25133889
TI - Carotid artery blood flow decreases after rapid head rotation in piglets.
AB - Modification of cerebral perfusion pressure and cerebral blood flow (CBF) are
crucial components of the therapies designed to reduce secondary damage after
traumatic brain injury (TBI). Previously we documented a robust decrease in CBF
after rapid sagittal head rotation in our well-validated animal model of diffuse
TBI. Mechanisms responsible for this immediate (<10 min) and sustained (~24 h)
reduction in CBF have not been explored. Because the carotid arteries are a major
source of CBF, we hypothesized that blood flow through the carotid arteries (Q)
and vessel diameter (D) would decrease after rapid nonimpact head rotation
without cervical spine injury. Four-week-old (toddler) female piglets underwent
rapid (<20 msec) sagittal head rotation without impact, previously shown to
produce diffuse TBI with reductions in CBF. Ultrasonographic images of the
bilateral carotid arteries were recorded at baseline (pre-injury), as well as
immediately after head rotation and 15, 30, 45, and 60 min after injury. Diameter
(D) and waveform velocity (V) were used to calculate blood flow (Q) through the
carotid arteries using the equation Q=(0.25)piD(2)V. D, V, and Q were normalized
to the pre-injury baseline values to obtain a relative change after injury in
right and left carotid arteries. Three-way analysis of variance and post-hoc
Tukey-Kramer analyses were used to assess statistical significance of injury,
time, and side. The relative change in carotid artery diameter and flow was
significantly decreased in injured animals in comparison with uninjured sham
controls (p<0.0001 and p=0.0093, respectively) and did not vary with side
(p>0.39). The average carotid blood velocity did not differ between sham and
injured animals (p=0.91). These data suggest that a reduction in global CBF after
rapid sagittal head rotation may be partially mediated by a reduction in carotid
artery flow, via vasoconstriction.
PMID- 25133891
TI - Good outcome of haploidentical hematopoietic SCT as a salvage therapy in children
and adolescents with acquired severe aplastic anemia.
AB - Haploidentical hematopoietic SCT (haplo-HSCT) is to be established in patients
with acquired severe aplastic anemia (SAA) refractory to immunosuppressive
therapy and lacking HLA-matched related or unrelated donors. Graft failure (GF)
and GVHD have been major obstacles to HSCT. A total of 17 children and
adolescents with SAA underwent haplo-HSCT in our center. The conditioning regimen
consisted of BU, fludarabine, CY and anti-thymocyte globulin. All patients
received cyclosporine, short-term MTX, mycophenolate mofetil and basiliximab for
GVHD prophylaxis. Mesenchymal stem cells derived from unrelated umbilical cord
were infused on day 1. Neutrophil engraftment was achieved in all 17 patients in
a median time of 16 days (range 9-25 days). The median time of platelet
engraftment was 22 days (range 9-95 days) in 16 patients. The cumulative
incidence (CI) of II-IV acute GVHD (aGVHD) at day +100 was 30.53+/-11.12% and III
IV aGVHD occurred in only one patient. The CI of chronic GVHD was 21.25+/-13.31%.
Secondary GF with autologous hematopoiesis recovery occurred in one patient. The
OS was 71.60+/-17.00% at a median follow-up of 362 (36-1321) days. These limited
promising data suggest that haplo-HSCT is feasible as a salvage therapy for
children and adolescents with refractory SAA who lack matched donors.
PMID- 25133892
TI - Long-term remission after high-dose chemotherapy followed by auto-SCT as
consolidation for intravascular large B-cell lymphoma.
PMID- 25133894
TI - Risk factor analysis of posterior reversible encephalopathy syndrome after
allogeneic hematopoietic SCT in children.
PMID- 25133895
TI - A golden opportunity.
PMID- 25133893
TI - Not too little, not too much-just right! (Better ways to give high dose
melphalan).
AB - Of the 13 286 autologous haematopoietic cell transplant procedures reported in
the US in 2010-2012 for plasma cell disorders, 10 557 used single agent, high
dose melphalan. Despite 30 years of clinical and pharmacokinetic (PK) experience
with high-dose melphalan, and its continuing central role as cytoreductive
therapy for large numbers of patients with myeloma, the pharmacodynamics and
pharmacogenomics of melphalan are still in their infancy. The addition of
protectant agents such as amifostine and palifermin allows dose escalation to 280
mg/m(2), but at these doses it is cardiac, rather than gut, toxicity that is dose
limiting. Although combination with additional alkylating agents is feasible, the
additional TRM may not be justified when so many post-consolidation therapies are
available for myeloma patients. Current research should optimise the delivery of
this single-agent chemotherapy. This includes the use of newer formulations and
real-time PKs. These strategies may allow a safe and effective platform for
adding synergistic novel therapies and provide a window of lymphodepletion for
the addition of immunotherapies.
PMID- 25133896
TI - Bortezomib/bendamustine/dexamethasone induced good PR in refractory relapse post
auto-SCT with constitutive RAS activation due to V600E BRAF mutation.
PMID- 25133897
TI - Tracheobronchomalacia after allogeneic BMT; pulmonary function test findings
similar to those of bronchiolitis obliterans.
PMID- 25133899
TI - Salt stress mitigation by seed priming with UV-C in lettuce plants: growth,
antioxidant activity and phenolic compounds.
AB - Seeds of Lactuca sativa L. 'Romaine' were subjected to priming treatments with UV
C radiation at 0.85 or 3.42 kJ m(-2). Seedlings obtained from both primed (Pr)
and non-primed (NPr) seeds were grown in an hydroponic culture system
supplemented with 0 (control) or 100 mM NaCl. After 21 days of NaCl treatment,
root and leaf biomass, root lengths, leaf numbers, and leaf surface area were
measured. Ions (Na(+) and K(+)) accumulation was determined in roots and leaves.
Total phenolic compound and flavonoid concentrations, as well as antioxidant and
antiradical activities were measured in L. sativa leaves. Salt stress resulted in
a lower increase in fresh weight of roots and leaves, which was more pronounced
in roots than in leaves, due to reduced root elongation, leaf number and leaf
expansion, as well as leaf thickness. The lower increase in fresh weight was
accompanied by a restriction in tissue hydration and K(+) ion uptake, as well as
an increase in Na(+) ion concentrations in all organs. These effects were
mitigated in plants from the UV-C primed seeds. The mitigating effect of UV-C was
more pronounced at 0.85 than at 3.42 kJ m(-2). Salt stress also resulted in an
increase in total phenolic compounds and flavonoid concentrations and in the
total antioxidant capacity in leaves. The highest diphenylpicrylhydrazyl radical
(DPPH) scavenging activity was found in the leaves of plants from both Pr seeds.
Our results suggest that plants grown from seed primed by exposure to moderate UV
C radiation exhibited a higher tolerance to salinity stress.
PMID- 25133898
TI - Sleep quality following hematopoietic stem cell transplantation: longitudinal
trajectories and biobehavioral correlates.
AB - The present study examined changes in sleep quality following hematopoietic stem
cell transplantation (HSCT) and investigated associations with biobehavioral
factors. Individuals undergoing HSCT for hematologic malignancies (N=228)
completed measures of sleep quality and psychological symptoms pre-transplant and
1, 3, 6 and 12 months post transplant. Circulating inflammatory cytokines (IL-6,
TNF-alpha) were also assessed. Sleep quality was poorest at 1 month post
transplant, improving and remaining relatively stable after 3 months post
transplant. However, approximately half of participants continued to experience
significant sleep disturbance at 6 and 12 months post transplant. Mixed-effects
linear regression models indicated that depression and anxiety were associated
with poorer sleep quality, while psychological well-being was associated with
better sleep. Higher circulating levels of IL-6 were also linked with poorer
sleep. Subject-level fixed effects models demonstrated that among individual
participants, changes in depression, anxiety and psychological well-being were
associated with corresponding changes in sleep after covarying for the effects of
time since transplant. Sleep disturbance was most severe when depression and
anxiety were greatest and psychological well-being was lowest. Findings indicate
that sleep disturbance is a persistent problem during the year following HSCT.
Patients experiencing depression or anxiety and those with elevated inflammation
may be at particular risk for poor sleep.
PMID- 25133900
TI - Biomass-directed synthesis of 20 g high-quality boron nitride nanosheets for
thermoconductive polymeric composites.
AB - Electrically insulating boron nitride (BN) nanosheets possess thermal
conductivity similar to and thermal and chemical stabilities superior to those of
electrically conductive graphenes. Currently the production and application of BN
nanosheets are rather limited due to the complexity of the BN binary compound
growth, as opposed to massive graphene production. Here we have developed the
original strategy "biomass-directed on-site synthesis" toward mass production of
high-crystal-quality BN nanosheets. The strikingly effective, reliable, and high
throughput (dozens of grams) synthesis is directed by diverse biomass sources
through the carbothermal reduction of gaseous boron oxide species. The produced
BN nanosheets are single crystalline, laterally large, and atomically thin.
Additionally, they assemble themselves into the same macroscopic shapes peculiar
to original biomasses. The nanosheets are further utilized for making
thermoconductive and electrically insulating epoxy/BN composites with a 14-fold
increase in thermal conductivity, which are envisaged to be particularly valuable
for future high-performance electronic packaging materials.
PMID- 25133901
TI - Beneficial health effects of Chios Gum Mastic and peroxisome proliferator
activated receptors: indications of common mechanisms.
AB - For thousands of years, Chios Gum Mastic (CGM), the resin produced by the trunk
of Pistachia lentiscus var Chia, has been used for culinary and medicinal
purposes and several therapeutic properties have been attributed to it. CGM has
been used in traditional medicine of various nations in the eastern Mediterranean
area. This survey was carried out to identify biological mechanisms that could
explain traditional usage and recent pharmacological findings. We reviewed the
related scientific literature available from the NCBI PUBMED database on CGM
studies and on natural products showing peroxisome proliferator-activated
receptor (PPAR) agonist effects. We investigated whether CGM qualifies as a PPAR
modulator. A large number of studies demonstrate that CGM has antioxidant, anti
inflammatory, hypolipidemic, and anticancer properties. Recently, the first
evidence of CGM antidiabetic effect became known. CGM chemical composition has
been extensively analyzed and the presence of several compounds, especially
triterpenoids is well documented. Some of them, oleanonic acid, oleanolic acid,
and gallic acid are considered to act as PPAR modulators. PPARs are nuclear
receptors functioning as transcription factors and thereby controlling cellular
functions at the level of gene expression. PPARs are involved in the pathways of
significant diseases, such as metabolic syndrome, diabetes mellitus,
dyslipidemia, inflammation, atheromatosis, and neoplasias, constituting a key
target for pharmacological interventions. This article proposes that the
synergistic action of some constituents of CGM on PPARs and more precisely on
both PPARs isotypes-alpha and -gamma, may be one of the major biological
mechanisms via which CGM exerts its multiple effects.
PMID- 25133902
TI - How we treat our own: the experiences and characteristics of psychology trainees
with disabilities.
AB - OBJECTIVE: To better understand the characteristics and experiences of
psychologists and trainees with disabilities. METHOD: An invitation to
participate in a survey of psychologists and psychology trainees with
disabilities was sent to professional listservs related to psychology and/or
disability. Fifty-six trainees and psychologists with doctoral training in
clinical, counseling, school, or rehabilitation psychology completed the survey.
Over half (57.1%) were practicing psychologists and 42.9% were current trainees.
The most commonly reported disabilities were physical, sensory, and chronic
health. RESULTS: The majority of the participants reported experiencing
disability-related discrimination during their training, and less than one third
had received mentorship from psychologists with disabilities. Less than half of
respondents disclosed their disability to a university disability services
office, and many relied on informal accommodations alone. Most participants did
not disclose their disability during the graduate school, internship, or
postdoctoral application processes. CONCLUSIONS: Professional psychology programs
and training sites should work to remove barriers and provide support for
trainees with disabilities, especially during preinternship doctoral training.
Programs should not expect disability services offices to provide all support for
students with disabilities, especially support related to clinical training.
PMID- 25133903
TI - Does slowed processing speed account for executive deficits in multiple
sclerosis? Evidence from neuropsychological performance and structural
neuroimaging.
AB - OBJECTIVE: Executive deficits and slow processing speed (PS) are observed in
persons with multiple sclerosis (MS). The question of whether executive deficits
can be explained by slow PS was examined with neuropsychological measures and a
neurostructural measure (brain atrophy). METHOD: Fifty MS patients were compared
with 28 healthy controls (HCs) on tasks of executive functioning with and without
a PS element (e.g., Trail Making Test and Wisconsin Card Sorting Test). RESULTS:
The MS group performed worse than HCs on speeded tasks of executive function.
However, after controlling for speed, group differences on executive tasks
disappeared. There were also no group differences on executive tasks with no PS
demands. The effect of disease progression on executive task performance was
assessed in the MS group. Higher atrophy in MS participants was associated with
greater deficits on speeded executive tasks, but this association disappeared
when controlling for PS. There was no association between atrophy and performance
on nonspeeded executive tasks. CONCLUSIONS: Our results support the notion that
executive deficits in MS may be explained by slow PS. These findings highlight
the role of slowed PS as a primary impairment underlying other cognitive
functions. Disentangling the relative contribution of PS to executive function is
an important step toward the development of appropriate rehabilitation strategies
for persons with MS.
PMID- 25133904
TI - Listeners' preference for computer-synthesized speech over natural speech of
people with disabilities.
AB - PURPOSE/OBJECTIVE: There are few controlled experimental studies that examine
reactions to people with speech disabilities. We conducted 2 studies designed to
examine participants' reactions to persuasive appeals delivered by people with
physical disabilities and mild to moderate dysarthria. RESEARCH METHOD/DESIGN:
Research participants watched video clips delivered by actors with bona fide
disabilities and subsequently rated the argument, message, and the speaker. The
first study (n = 165) employed a between-groups design that examined reactions to
natural dysarthric speech, synthetic speech as entered into a keyboard by hand,
and synthetic speech as entered into a keyboard with a headwand. The second study
(n = 27) employed a within-groups design that examined how participants reacted
to natural dysarthric speech versus synthetic speech as entered into a keyboard
by hand. RESULTS: Both of these studies provide evidence that people rated the
argument, message, and speaker more favorably when people with disabilities used
synthetic speech than when they spoke in their natural voice.
CONCLUSIONS/IMPLICATIONS: The implications are that although people react
negatively to computer-synthesized speech, they prefer it to and find it more
persuasive than the speech of people with disabilities. This appears to be the
case even if the speech is only moderately impaired and is as intelligible as the
synthetic speech. Hence, the decision to use synthetic speech versus natural
speech can be further complicated by an understanding that even the intelligible
speech of people with disabilities leads to more negative reactions than
synthetic speech.
PMID- 25133906
TI - Stability of vocational interests after recent spinal cord injury.
AB - OBJECTIVE: We sought to identify the stability of vocational interests among
persons with spinal cord injury (SCI) first assessed during inpatient
rehabilitation. DESIGN: Initial assessments were completed during inpatient
rehabilitation an average of 50 days after SCI onset (n = 521). Follow-up
measures, collected by mail, were obtained an average of 16.6 months postinjury
(n = 190) and 29.1 months postinjury (n = 296). Participants (n = 135) completed
all 3 assessments. Participants completed the 1994 Strong Interest Inventory
(Campbell, 1971; Harmon, Hansen, Borgen, & Hammer, 1994), Form T317, a 317-item
measure of vocational interests. RESULTS: Comparison of scale means across 3
times of measurement indicated significant changes in 2 of 6 general occupational
themes (GOT), 8 basic interest scales (BIS), and 2 special scales (leadership
style, risk taking/adventure). With 1 exception, a linear trend indicating an
increase in reported interests accounted for observed relationships. An age by
time interaction occurred with 1 GOT and 3 BIS. The average stability coefficient
was 0.61 for the GOT, 0.59 for the BIS, and 0.70 for the special scales. The
average coefficients were somewhat lower for the oldest participants. CONCLUSION:
Interests do not appear to be static when first measured during inpatient
rehabilitation after SCI. Rather, they evolve with average increases on select
themes more compatible with the limitations of SCI. Stability coefficients
suggest that interests are likely to change more than indicated in earlier
studies.
PMID- 25133905
TI - Effort in acute traumatic brain injury: considering more than pass/fail.
AB - PURPOSE/OBJECTIVE: Performance validity is often conceptualized as a dichotomous
process. Effort likely lies on a continuum, however, and psychologists' tendency
to rely on pass/fail descriptors of one's effort may not be the only approach.
The current study aims to show that when performance validity is considered on a
continuum, it may provide clinical information related to cognitive functioning.
RESEARCH METHOD/DESIGN: Forty-four patients with moderate or severe traumatic
brain injury were evaluated with the Repeatable Battery for the Assessment of
Neuropsychological Status upon their emergence from posttraumatic amnesia. From
this data, previously developed effort index scores and "other cognitive
functions" index scores were calculated. RESULTS: Performance on the effort index
significantly accounted for the patients' performance on a cognitive composite
score after considering education and severity of injury.
CONCLUSIONS/IMPLICATIONS: Findings suggest that more in-depth analysis of
validity test performance is beneficial to gauge a patient's level of effort and
is important to consider when interpreting results and in treatment planning.
PMID- 25133907
TI - Coping strategies and resources as predictors of psychosocial adaptation among
people with spinal cord injury.
AB - PURPOSE: The onset of a spinal cord injury (SCI) is accompanied by a massive
amount of stress, on which professionals in the medical field focus attention and
care. The subsequent cascade of psychological stressors related to SCI often
receives lesser attention. When individuals experience new forms of stress, they
typically respond with attempts to cope, which may or may not be adaptive in
reducing their stress levels. The twofold purpose of this study was to
investigate whether SCI survivors' use of coping resources (i.e., hope, sense of
coherence) and coping strategies (e.g., engagement coping, seeking social
support) influences their psychosocial adaptation, and whether their use of
coping strategies moderates the effect of coping resources, after controlling for
the influence of depression and anxiety, on psychosocial adaptation. DESIGN: This
cross-sectional study involved a self-report survey of survivors of SCI.
Inclusion criteria included: (a) being 18 years of age or older, (b) having
received inpatient rehabilitation services following the SCI, and (c) not having
traumatic head injury at the time of the SCI onset. PARTICIPANTS: The sample
consisted of 95 individuals with SCI who received outpatient rehabilitation
services at a center in the midsouthern United States. RESULTS: Results indicated
that coping resources and coping strategies were significantly associated with
psychosocial adaptation. Furthermore, engagement coping explained a significant
portion of the variance in psychosocial adaptation both individually and as an
interactive variable with the 2 coping resources of sense of coherence and hope.
CONCLUSIONS: Findings indicate that both coping resources and strategies
(especially engagement coping) are reliably linked to adaptation to SCI. The
findings further suggest that engagement coping positively influences
psychosocial adaptation even when coping resources are mostly absent. Other
implications for the field of rehabilitation are briefly outlined.
PMID- 25133915
TI - Symmetrized photoinitiated electron flow within the [myoglobin:cytochrome b5]
complex on singlet and triplet time scales: energetics vs dynamics.
AB - We report here that photoinitiated electron flow involving a metal-substituted (M
= Mg, Zn) myoglobin (Mb) and its physiological partner protein, cytochrome b5
(cyt b5) can be "symmetrized": the [Mb:cyt b5] complex stabilized by three D/E ->
K mutations on Mb (D44K/D60K/E85K, denoted MMb) exhibits both oxidative and
reductive ET quenching of both the singlet and triplet photoexcited MMb states,
the direction of flow being determined by the oxidation state of the cyt b5
partner. The first-excited singlet state of MMb ((1)MMb) undergoes ns-time scale
reductive ET quenching by Fe(2+)cyt b5 as well as ns-time scale oxidative ET
quenching by Fe(3+)cyt b5, both processes involving an ensemble of structures
that do not interconvert on this time scale. Despite a large disparity in driving
force favoring photooxidation of (1)MMb relative to photoreduction (delta(
DeltaG(0)) ~ 0.4 eV, M = Mg; ~ 0.2 eV, M = Zn), for each M the average rate
constants for the two reactions are the same within error, (1)k(f) > 10(8) s(-1).
This surprising observation is explained by considering the driving-force
dependence of the Franck-Condon factor in the Marcus equation. The triplet state
of the myoglobin ((3)MMb) created by intersystem crossing from (1)MMb likewise
undergoes reductive ET quenching by Fe(2+)cyt b5 as well as oxidative ET
quenching by Fe(3+)cyt b5. As with singlet ET, the rate constants for oxidative
ET quenching and reductive ET quenching on the triplet time scale are the same
within error, (3)k(f) ~ 10(5) s(-1), but here the equivalence is attributable to
gating by intracomplex conversion among a conformational ensemble.
PMID- 25133916
TI - A false dichotomy? Mental illness and lone-actor terrorism.
AB - We test whether significant differences in mental illness exist in a matched
sample of lone- and group-based terrorists. We then test whether there are
distinct behavioral differences between lone-actor terrorists with and without
mental illness. We then stratify our sample across a range of diagnoses and again
test whether significant differences exist. We conduct a series of bivariate,
multivariate, and multinomial statistical tests using a unique dataset of 119
lone-actor terrorists and a matched sample of group-based terrorists. The odds of
a lone-actor terrorist having a mental illness is 13.49 times higher than the
odds of a group actor having a mental illness. Lone actors who were mentally ill
were 18.07 times more likely to have a spouse or partner who was involved in a
wider movement than those without a history of mental illness. Those with a
mental illness were more likely to have a proximate upcoming life change, more
likely to have been a recent victim of prejudice, and experienced proximate and
chronic stress. The results identify behaviors and traits that security agencies
can utilize to monitor and prevent lone-actor terrorism events. The correlated
behaviors provide an image of how risk can crystalize within the individual
offender and that our understanding of lone-actor terrorism should be
multivariate in nature.
PMID- 25133917
TI - Short-sighted confession decisions: the role of uncertain and delayed
consequences.
AB - Suspects have a propensity to focus on short-term contingencies, giving
disproportionate weight to the proximal consequences that are delivered by police
during an interrogation, and too little consideration to the distal (and often
more severe) consequences that may be levied by the judicial system if they are
convicted. In this research, the authors examined whether the perceived
uncertainty and temporal distance of distal consequences contribute to this
propensity. Using the repetitive question paradigm (Madon et al., 2012),
participants (N = 209) were interviewed about 20 prior criminal and unethical
behaviors and were required to admit or deny each one. Participants' denials and
admissions were paired with both a proximal consequence and a distal consequence,
respectively. Results indicated that the distal consequence had less impact on
participants' admission decisions when it was uncertain and temporally remote.
These results provide evidence that the perceived uncertainty and temporal
distance of future punishment are key factors that lead suspects to confess to
crimes in exchange for short-term gains.
PMID- 25133919
TI - Selecting fillers on emotional appearance improves lineup identification
accuracy.
AB - Mock witnesses sometimes report using criminal stereotypes to identify a face
from a lineup, a tendency known as criminal face bias. Faces are perceived as
criminal-looking if they appear angry. We tested whether matching the emotional
appearance of the fillers to an angry suspect can reduce criminal face bias. In
Study 1, mock witnesses (n = 226) viewed lineups in which the suspect had an
angry, happy, or neutral expression, and we varied whether the fillers matched
the expression. An additional group of participants (n = 59) rated the faces on
criminal and emotional appearance. As predicted, mock witnesses tended to
identify suspects who appeared angrier and more criminal-looking than the
fillers. This tendency was reduced when the lineup fillers matched the emotional
appearance of the suspect. Study 2 extended the results, testing whether the
emotional appearance of the suspect and fillers affects recognition memory.
Participants (n = 1,983) studied faces and took a lineup test in which the
emotional appearance of the target and fillers was varied between subjects.
Discrimination accuracy was enhanced when the fillers matched an angry target's
emotional appearance. We conclude that lineup member emotional appearance plays a
critical role in the psychology of lineup identification. The fillers should
match an angry suspect's emotional appearance to improve lineup identification
accuracy.
PMID- 25133918
TI - Criminogenic factors, psychotic symptoms, and incident arrests among people with
serious mental illnesses under intensive outpatient treatment.
AB - Although research robustly indicates that general or "criminogenic" factors
predict various measures of recidivism, there is controversy about the extent to
which these factors, versus untreated symptoms, lead to justice involvement for
people with mental illnesses. Based on a sample of 183 people in intensive
outpatient treatment followed for an average period of 34.5 months, the present
study tested whether criminogenic factors (i.e., factor-analytically derived
proxies of some of the "Central Eight"; Andrews & Bonta, 2010) and psychotic
symptoms were independently associated with arrest. The study also compared the
predictive utility of these domains. In the fully adjusted model, the antisocial
subscale and male sex were associated with increased arrest rates, whereas
psychosis and age were associated with decreased arrest rates. Criminogenic
factors and psychotic symptoms had comparable predictive utility. We conclude
that criminogenic factors-chiefly arrest history-and psychotic symptoms predict
arrest rates. Both sets of variables appear useful for assessing risk of arrest
among people with mental illnesses who are not under current correctional
supervision.
PMID- 25133920
TI - Examining the impact of sexism on evaluations of social scientific evidence in
discrimination litigation.
AB - The present 2 studies involved undergraduate participants and investigated
whether various types of sexism and other correlated predictors, such as
political conservatism and scientific discounting, can predict people's
evaluations of social science research on sex stereotypes, sexism, and sex
discrimination. In Study 1, participants high in hostile sexism, scientific
discounting, and/or political conservatism were more critical of scientific
studies that provided evidence for sexism than identical studies showing null
results. Study 2 showed that participants high in modern sexism, hostile sexism,
and political conservatism evaluated social scientific studies more negatively;
in addition, assessments of social scientific evidence quality mediated the
effect of modern sexism on admissibility ratings (b = -0.15, z = -4.16, p = .00).
Overall, these results suggest that sexist beliefs can bias one's judgments of
social scientific evidence. Future research should explore whether the same
psychological processes operate for judges and jurors as they evaluate the
admissibility of evidence and examine ways to attenuate the effect of sexism on
evaluations.
PMID- 25133921
TI - Reporting guidance for violence risk assessment predictive validity studies: the
RAGEE Statement.
AB - Available reporting guidelines for prognostic and diagnostic accuracy studies
apply primarily to biological assessment and outcomes, overlooking behavioral
issues with major public health and safety implications such as violence. The
present study aimed to develop the first set of reporting guidance for predictive
validity studies of violence risk assessments: the Risk Assessment Guidelines for
the Evaluation of Efficacy (RAGEE) Statement. A systematic search of 8 electronic
databases prior to September 2012 identified 279 reporting guidelines for
prognostic and diagnostic accuracy studies. Unique items were extracted and
modified to make them relevant to risk assessment. A 4-wave Delphi process
involving a multidisciplinary team of 37 international experts resulted in a 50
item reporting checklist. The panelists endorsed the RAGEE Statement checklist as
being highly satisfactory and as indicating study features that should be
reported routinely in manuscripts. Use of these proposed standards has the
potential to improve the quality of the risk assessment literature.
PMID- 25133922
TI - First-principles study on doping effects of sodium in kesterite Cu2ZnSnS4.
AB - A sodium impurity is inevitable for Cu2ZnSnS4 on a substrate of soda-lime glass
during high-temperature processing. Recently, it was found that a sodium impurity
could improve the photovoltaic properties of Cu2ZnSnS4-based thin film solar
cells (including influencing crystallinity, affecting grain growth, increasing
hole density, shifting the acceptor level closer to the conduction band,
increasing carrier concentration, elongating minority carrier lifetime, and so
on). Thus, sodium doping becomes an effective modification means for Cu2ZnSnS4 on
the flexible substrate. However, there are some examples available in the
literature that discuss the underlying physical mechanism. In the present work,
the crystal structure, electronic structure, and optical properties of sodium
occupying different lattice sites or interstitial sites of kesterite Cu2ZnSnS4
were systematically calculated by density functional theory within the GGA+U
method. Na impurity favors occupation of the interstitial sites. If Na impurity
occupies the cation lattice sites, the band gap of Cu2ZnSnS4 will be broadened,
which is opposite to the situation of an Na impurity occupying the interstitial
sites. The doping effects of Na in Cu2ZnSnS4 are mainly exhibited by the
following aspects: energy band shifting, energy band broadening or narrowing, and
effective mass of holes on the top of valence band reduction. The calculated
results in the present work not only confirm experimental observationa in
published articles but also provide an in-depth understanding of them. Thus, the
findings could help to promote novel, high-efficiency Cu2ZnSnS4-based thin-film
solar cells.
PMID- 25133925
TI - Electroaddressing of ZnS quantum dots by codeposition with chitosan to construct
fluorescent and patterned device surface.
AB - Electroaddressing is an attractive method for triggering assembly of stimuli
responsive biopolymers with exquisite spatiotemporal control, and it also offers
a controllable means to concurrently assemble biological materials and
nanoparticles for a diverse range of applications. Here, we demonstrate a novel
method to construct fluorescent and patterned device surfaces by
electroaddressing of quantum dots (QDs)/chitosan composite. First, the surfaces
of ZnS QDs/chitosan composite on the electrodes are built by electrodeposition
method. It is shown that the deposited surface displays clear fluorescence under
UV light, and the fluorescence intensity of the surface can be controlled by
electrodeposition conditions (e.g., deposition time). Furthermore, a variety of
fluorescent patterns can be constructed by employing electrodes or substrates
with various shapes. Specifically, taking advantage of the spatiotemporal
selectivity of electroaddressing and the pH-responsive property of chitosan, we
construct diverse fluorescent patterns by electroaddressing QDs/chitosan
composite at the localized region. It is also found that the fluorescent patterns
of QDs/chitosan composite have reproducibility. Thus, this work presents a
convenient, versatile, and controllable method to construct fluorescent and
patterned device surface by electroaddressing, which has promising applications
in photoluminescence device, fluorescent and patterned coating, and nanocomposite
biodevice.
PMID- 25133926
TI - Breaking down number syntax: spared comprehension of multi-digit numbers in a
patient with impaired digit-to-word conversion.
AB - Can the meaning of two-digit Arabic numbers be accessed independently of their
verbal-phonological representations? To answer this question we explored the
number processing of ZN, an aphasic patient with a syntactic deficit in digit-to
verbal transcoding, who could hardly read aloud two-digit numbers, but could read
them as single digits ("four, two"). Neuropsychological examination showed that
ZN's deficit was neither in the digit input nor in the phonological output
processes, as he could copy and repeat two-digit numbers. His deficit thus lied
in a central process that converts digits to abstract number words and sends this
information to phonological retrieval processes. Crucially, in spite of this
deficit in number transcoding, ZN's two-digit comprehension was spared in several
ways: (1) he could calculate two-digit additions; (2) he showed good performance
in a two-digit comparison task, and a continuous distance effect; and (3) his
performance in a task of mapping numbers to positions on an unmarked number line
showed a logarithmic (nonlinear) factor, indicating that he represented two-digit
Arabic numbers as holistic two-digit quantities. Thus, at least these aspects of
number comprehension can be performed without converting the two-digit number
from digits to verbal representation.
PMID- 25133927
TI - Decoding letter position in word reading.
AB - A fundamental computation underlying visual word recognition is the ability to
transform a set of letters into a visual word form. Neuropsychological data
suggest that letter position within a word may be independently affected by brain
damage, resulting in a dissociable subtype of peripheral dyslexia. Here we used
functional magnetic resonance imaging and supervised machine learning techniques
to classify letter position based on activation patterns evoked during reading
Hebrew words. Across the entire brain, activity patterns in the left
intraparietal sulcus provided the best classification accuracy (80%) with respect
to letter position. Importantly, the same set of voxels that showed highest
classification performance of letter position using one letter-of-interest also
showed highest classification performance using a different letter-of-interest. A
functional connectivity analysis revealed that activity in these voxels co-varied
with activity in the Visual Word Form Area, confirming cross-talk between these
regions during covert reading. The results converge with reports of patients with
acquired letter position dyslexia, who suffer from left occipito-parietal
lesions. These findings provide direct and novel evidence for the role of left
IPS within the reading network in processing relative letter positions.
PMID- 25133923
TI - Design, synthesis, and biological evaluation of (3R)-1,2,3,4-tetrahydro-7-hydroxy
N-[(1S)-1-[[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-2
methylpropyl]-3-isoquinolinecarboxamide (JDTic) analogues: in vitro pharmacology
and ADME profile.
AB - JDTic analogues 4-15 which have the hydroxyl groups replaced with other groups
were synthesized and their in vitro efficacy at the MU, delta, and kappa opioid
receptors determined and compared to JDTic using [(35)S]GTPgammaS assays.
Compounds 4, 5, 6, 13, 14, and 15 had Ke = 0.024, 0.01, 0.039, 0.02, 0.11, and
0.041 nM compared to the Ke = 0.02 nM for JDTic at the kappa receptor and were
highly selective for the kappa receptor relative to the MU and delta opioid
receptors. Unexpectedly, replacement of the 3-hydroxyl substituent of the 4-(3
hydroxyphenyl) group of JDTic with a H, F, or Cl substituent leads to potent and
selective KOR antagonists. In vitro studies to determine various ADME properties
combined with calculated TPSA, clogP, and logBB values suggests that the potent
and selective kappa opioid receptors 4, 5, 13, and 14 deserve consideration for
further development toward potential drugs for CNS disorders.
PMID- 25133929
TI - Covalency of hydrogen bonds in solids revisited.
AB - The covalent nature of short hydrogen bonds has been under debate for long. Here
we show that the crystal orbital Hamilton population (COHP) bonding indicator
gives new, complementary evidence of covalent hydrogen...acceptor interactions in
the molecular solid state.
PMID- 25133928
TI - Cystine stones: a single tertiary center experience.
AB - OBJECTIVE: To analyze the epidemiological and clinical characteristics and
therapeutic outcomes of patients with cystine stones and to compare them with the
characteristics of patients with calcium oxalate stones. PATIENTS AND METHODS: We
identified 30 patients with cystine stones who were consulted in our department
from January 1972 until December 2013. These patients were matched and paired,
based on age and gender, to 30 calcium oxalate stone formers who were diagnosed
and treated in our department from January 2011 until December 2013. RESULTS:
Cystine stones were significantly large in size (p<0.001) and most of them were
found in the kidney (p=0.002). Patients with cystinuria had their first stone
episode at an early age (p<0.001) compared with patients with calcium oxalate
stones. No significant differences were observed regarding the frequency and the
severity of symptoms. Both groups had similar visits per year in outpatient
clinics, emergency room admissions, and episodes of febrile urinary tract
infections. Cystine stone formers had undergone significantly higher number of
procedures for stone removal (p<0.001). No statistical differences were found in
the compliance rates between the groups. Patients with cystine stones had
significantly higher serum creatinine levels (p=0.005). CONCLUSIONS: Cystine
stones present in an earlier age and have the likelihood to be large in size.
Patients with cystine stones undergo a greater number of procedures, and they
have a greater risk to develop chronic renal impairment.
PMID- 25133930
TI - Zinc blende versus wurtzite ZnS nanoparticles: control of the phase and optical
properties by tetrabutylammonium hydroxide.
AB - The influence of tetrabutylammonium hydroxide on the phase composition (cubic
zinc blende versus hexagonal wurtzite) of ZnS nanoparticles was studied. The ZnS
nanoparticles were prepared by a microwave-assisted solvothermal method, and the
phase structure and optical properties along with the growth process of ZnS
nanoparticles were studied. We report XRD, FE-SEM, EDXS, UV-vis and PL
measurements, and first-principles calculations based on TDDFT methods in order
to investigate the structural and electronic properties and the growth mechanism
of ZnS nanostructures. The effects as well as the merits of microwave heating on
the process and characteristics of the obtained ZnS nanostructures and their
performance are reported.
PMID- 25133931
TI - ALPPS: Short-term Outcome and Functional Changes in the Future Liver Remnant.
PMID- 25133932
TI - Perioperative hyperglycemia and risk of adverse events among patients with and
without diabetes.
AB - OBJECTIVE: To study the association between diabetes status, perioperative
hyperglycemia, and adverse events in a statewide surgical cohort. BACKGROUND:
Perioperative hyperglycemia may increase the risk of adverse events more
significantly in patients without diabetes (NDM) than in those with diabetes
(DM). METHODS: Using data from the Surgical Care and Outcomes Assessment Program,
a cohort study (2010-2012) evaluated diabetes status, perioperative
hyperglycemia, and composite adverse events in abdominal, vascular, and spine
surgery at 53 hospitals in Washington State. RESULTS: Among 40,836 patients (mean
age, 54 years; 53.6% women), 19% had diabetes; 47% underwent a perioperative
blood glucose (BG) test, and of those, 18% had BG >=180 mg/dL. DM patients had a
higher rate of adverse events (12% vs 9%, P < 0.001) than NDM patients. After
adjustment, among NDM patients, those with hyperglycemia had an increased risk of
adverse events compared with those with normal BG. Among NDM patients, there was
a dose-response relationship between the level of BG and composite adverse events
[odds ratio (OR), 1.3 for BG 125-180 (95% confidence interval (CI), 1.1-1.5); OR,
1.6 for BG >=180 (95% CI, 1.3-2.1)]. Conversely, hyperglycemic DM patients did
not have an increased risk of adverse events, including those with a BG 180 or
more (OR, 0.8; 95% CI, 0.6-1.0). NDM patients were less likely to receive insulin
at each BG level. CONCLUSIONS: For NDM patients, but not DM patients, the risk of
adverse events was linked to hyperglycemia. Underlying this paradoxical effect
may be the underuse of insulin, but also that hyperglycemia indicates higher
levels of stress in NDM patients than in DM patients.
PMID- 25133933
TI - Coating and enhanced photocurrent of vertically aligned zinc oxide nanowire
arrays with metal sulfide materials.
AB - Hybrid nanostructures combining zinc oxide (ZnO) and a metal sulfide (MS)
semiconductor are highly important for energy-related applications. Controlled
filling and coating of vertically aligned ZnO nanowire arrays with different MS
materials was achieved via the thermal decomposition approach of single-source
precursors in the gas phase by using a simple atmospheric-pressure chemical vapor
deposition system. Using different precursors allowed us to synthesize
multicomponent structures such as nanowires coated with alloy shell or multishell
structures. Herein, we present the synthesis and structural characterization of
the different structures, as well as an electrochemical characterization and a
photovoltaic response of the ZnO-CdS system, in which the resulting photocurrent
upon illumination indicates charge separation at the interface.
PMID- 25133935
TI - A pilot study of manual chronic partial exchange transfusion in children with
sickle disease.
AB - Objective Red cell exchange transfusion is frequently used in the management of
patients with sickle cell disease (SCD) either electively or chronically to
maintain hemoglobin S (HbS) <30%. The purpose of this retrospective study was to
evaluate the results of manual chronic partial exchange transfusion (MCPET) on
level of Hb and HbS, on iron load and on the need for chelation, on risk of
immunization, monitoring transfusion-transmitted viral infection, and clinical
outcome. Methods We reviewed the long-term effect of MCPET in 10 children (six
men and four women) with SCD and evaluated the iron balance during a median
follow-up of 20 months (range: 6-36) in which 248 exchanges were performed.
Results The pre-exchange median Hb value was 9.5 g/dl (range: 7.7-10.9 g/dl) and
the median post-exchange value was 9.4 g/dl (range: 8.4-11.1 g/dl).The majority
of patients reached an HbS of <50% with a median HbS value of 40.04% (range: 30
54). At start of the MCPET program, the median ferritin was 439 ng/ml (range: 80
1704 ng/ml). In the final evaluation, the median value of ferritin was 531 ng/ml
(range: 84-3840 ng/ml). The annual calculated iron balance was 0. 28 +/- 0.08
mg/kg/day. MCPET was well tolerated, and adverse effects were limited. Discussion
MCPET in children with SCD is safe to prevent iron overload, and is effective and
easy to use in our cohort. Conclusion Indication for chronic exchange blood
transfusion is essential for patients with SCD with recurrent and frequent crises
who do not respond to hydroxyurea. However, there is no consensual study for the
period at which chronic transfusion can safely be stopped and further research in
large population of patients with SCD will need to clarify this question.
PMID- 25133934
TI - Development of BODIPY FL vindoline as a novel and high-affinity pregnane X
receptor fluorescent probe.
AB - The pregnane X receptor (PXR) regulates the metabolism and excretion of
xenobiotics and endobiotics by regulating the expression of drug-metabolizing
enzymes and transporters. The unique structure of PXR allows it to bind many
drugs and drug leads, possibly causing undesired drug-drug interactions.
Therefore, it is crucial to evaluate whether chemicals or drugs bind to PXR.
Fluorescence-based assays are preferred because of their sensitivity and
nonradioactive nature. On the basis of our previously characterized 4 (BODIPY FL
vinblastine), a high-affinity PXR probe, we developed 20 (BODIPY FL vindoline)
and showed that it is a novel and potent PXR fluorescent probe with Kd of 256 nM
in a time-resolved fluorescence resonance energy transfer (TR-FRET) binding assay
with PXR. By using 20 (BODIPY FL vindoline) in the PXR TR-FRET assay, we obtained
a more than 7-fold signal-to-background ratio and high signal stability (signal
was stable for at least 120 min, and Z'-factor > 0.85 from 30 to 240 min). The
assay can tolerate DMSO up to 2%. This assay has been used to evaluate a panel of
PXR ligands for their PXR-binding affinities. The performance of 20 (BODIPY FL
vindoline) in the PXR TR-FRET assay makes it an ideal PXR fluorescent probe, and
the newly developed PXR TR-FRET assay with 20 (BODIPY FL vindoline) as a
fluorescent probe is suitable for high-throughput screening to identify PXR
binding ligands.
PMID- 25133936
TI - Urinary catheterization -- when good intentions go awry: a teachable moment.
PMID- 25133937
TI - Surface complexation reaction for phase transfer of hydrophobic quantum dot from
nonpolar to polar medium.
AB - Chemical reaction between oleate-capped Zn(x)Cd(1-x)S quantum dots (Qdots) and 8
hydroxyquinoline (HQ) led to formation of a surface complex, which was
accompanied by transfer of hydrophobic Qdots from nonpolar (hexane) to polar
(water) medium with high efficiency. The stability of the complex on the surface
was achieved via involvement of dangling sulfide bonds. Moreover, the transferred
hydrophilic Qdots--herein called as quantum dot complex (QDC)--exhibited new and
superior optical properties in comparison to bare inorganic complexes with
retention of the dimension and core structure of the Qdots. Finally, the new and
superior optical properties of water-soluble QDC make them potentially useful for
biological--in addition to light emitting device (LED)--applications.
PMID- 25133938
TI - A bird's eye view of anisatin induced convulsive seizures in brain by a (1)H NMR
based metabolic approach.
AB - Anisatin is the main convulsant component in plants of the genus Illicium, many
of which are important spices or folk medicines. The neurotoxicity of anisatin
has been widely investigated, mainly focusing on its action on the gamma-amino
butyrate (GABA) system; however, little is known about the metabolic alterations
that it causes. In this study, a NMR-based metabolomic approach was performed on
the extracts of cortexes and cerebellums of mice administered with anisatin to
explore the metabolic events associated with its intoxication. Orthogonal partial
least squares-discriminant analysis (OPLS-DA) revealed many differential
metabolites that indicated metabolic disturbance in neurotransmission and
neuromodulation (GABA, glutamate, glutamine, and taurine), stress of reactive
oxygen species (ROS) (ascorbate, phosphatidylcholine, choline, and ethanolamine),
energy metabolism (NAD(+)i.e., nicotinamide-adenine dinucleotide, lactate,
citrate, fumarate, creatine/phosphocreatine, and creatinine), amino acid
metabolism (leucine, isoleucine, valine, phenylalanine, tyrosine, tryptophan,
alanine, threonine, and glycine) and nucleic acid metabolism (NAD(+),
nicotinamide/niacinamide, adenosine, and guanosine). This pilot metabolomic study
on anisatin intoxication should help to develop a holistic view of convulsive
seizures induced by anisatin, and provide a better understanding of the
mechanisms.
PMID- 25133939
TI - Implementing a graduate medical education campaign to reduce or eliminate
potentially wasteful tests or procedures.
PMID- 25133940
TI - Efficacy and safety of histamine-2 receptor antagonists.
AB - IMPORTANCE: Histamine-2 receptor antagonists (H2RAs) are frequently used in the
treatment of gastroesophageal reflux disease (GERD) in children; however, their
efficacy and safety is questionable. OBJECTIVE: To systematically review the
literature to assess the efficacy and safety of H2RAs in pediatric GERD. EVIDENCE
REVIEW: PubMed, EMBASE, and the Cochrane database were searched for randomized
clinical trials investigating the efficacy and safety of H2RAs in pediatric GERD.
Two reviewers independently extracted data from the included articles. The
quality of the evidence was assessed using the Grades of Recommendations,
Assessment, Development, and Evaluation approach. When possible, infants and
children were analyzed separately. FINDINGS: Eight studies with a total of 276
children (0-15 years of age) were included. Compared with the placebo, H2RAs were
more effective in the reduction of symptoms in terms of histologic healing and
increasing gastric pH and had a larger overall treatment effect. In infants,
H2RAs were only more effective in terms of histologic healing. Comparing H2RAs
with antacids, H2RAs were more effective in symptom reduction in only 1 study.
H2RAs compared with proton pump inhibitors were not significantly different in
any of the outcome measures. For safety analysis, data were not reported in a
quantitative manner and for all outcomes, the quality of evidence was very low.
CONCLUSIONS AND RELEVANCE: Evidence to support the efficacy and safety of H2RAs
in infants and children is limited and of poor quality. Well-designed placebo
controlled trials are needed before thorough conclusions can be drawn.
PMID- 25133941
TI - Oxygen Cost of Recreational Horse-Riding in Females.
AB - BACKGROUND: The purpose of this study was to characterize the physiological
demands of a riding session comprising different types of recreational horse
riding in females. METHODS: Sixteen female recreational riders (aged 17 to 54
years) completed an incremental cycle ergometer exercise test to determine peak
oxygen consumption (VO2peak) and a 45-minute riding session based upon a British
Horse Society Stage 2 riding lesson (including walking, trotting, cantering and
work without stirrups). Oxygen consumption (VO2), from which metabolic equivalent
(MET) and energy expenditure values were derived, was measured throughout.
RESULTS: The mean VO2 requirement for trotting/cantering (18.4 +/- 5.1 ml.kg
1.min-1; 52 +/- 12% VO2peak; 5.3 +/- 1.1 METs) was similar to walking/trotting
(17.4 +/- 5.1 ml.kg-1.min-1; 48 +/- 13% VO2peak; 5.0 +/- 1.5 METs) and
significantly higher than for work without stirrups (14.2 +/- 2.9 ml.kg-1.min-1;
41 +/- 12% VO2peak; 4.2 +/- 0.8 METs) (P = .001). CONCLUSIONS: The oxygen cost of
different activities typically performed in a recreational horse riding session
meets the criteria for moderate intensity exercise (3-6 METs) in females, and
trotting combined with cantering imposes the highest metabolic demand. Regular
riding could contribute to the achievement of the public health recommendations
for physical activity in this population.
PMID- 25133942
TI - From the editor. Benefits of physical activity in the later years.
PMID- 25133943
TI - The relationship between physical activity and perceived health status in older
women: findings from the Woman's College Alumni Study.
AB - Using data collected from the Woman's College (WC) Alumni Study, the purpose of
this study was to determine whether perceived health status is related to
physical activity in older women. A multiple linear regression analysis was
conducted to examine the relationship between amounts of physical activity and
self-reported health status. The results of the current study reveal that the
level of physical activity is significantly correlated with perceived health
status. The findings of this study have implications for the assessment of older
individuals' health and may lead to interventions that are tailored to increase
physical activity among older women.
PMID- 25133944
TI - Physical and mental health correlates of self-efficacy in dementia family
caregivers.
AB - This study examined whether self-efficacy for controlling upsetting caregiving
thoughts would longitudinally predict mental and physical health as well as
utilization of psychotropic medications in help-seeking dementia family
caregivers (N = 53). Positive associations were found between self-efficacy and
self-reported mental health and physical health subscales of the Short Form
Health Questionnaire-12, and negative correlations were found between self
efficacy for controlling upsetting thoughts about caregiving and the number of
psychotropic medications being utilized both cross-sectionally and
longitudinally. These results suggest that self-efficacy for controlling
upsetting thoughts may be a fruitful target area for further intervention
research with dementia family caregivers.
PMID- 25133945
TI - Generational juggling acts in midlife families: gendered and ethnocultural
intersections.
AB - This study draws upon a sociocultural stress and coping perspective to examine
generational demands in midlife families. It examines both the predictors and
family-related circumstances that contribute to perceptions of greater demand,
with a focus on gendered and ethnocultural dimensions. Using mixed-methods, data
are based on a sample of 236 parents collected in 2006/2007 from four cultural
groups: British-, Chinese-, Southern European-, and South Asian Canadian. Key
findings reveal that caregiving experiences remain highly gendered and are
mediated by ethnocultural background and other work/family contextual
characteristics. Recommendations for those who work directly with culturally
diverse "sandwiched" generation families are highlighted.
PMID- 25133946
TI - Attitudes and stereotypes regarding older women and HIV risk.
AB - Persons aged 50 years and over will soon disproportionately represent the future
of the HIV/AIDS epidemic. It is estimated that by 2015 older adults will
represent 50% of persons living with HIV in the United States. Despite the
HIV/AIDS growing population among older adults, attitudes, beliefs, and
stereotypes toward older adults that exist in general society have affected HIV
prevention, education, and care. Specifically, ageist attitudes about the
sexuality of older adults in general and older women in particular, low clinical
HIV suspicion among healthcare providers, lack of knowledge about risk among
older women, and differentials in power related to negotiating sexual practices
all lead to heightened concerns for the prevention, identification, and treatment
of HIV disease in mature women. This article examines common attitudes, beliefs,
and stereotypes that exist within general society as well as health and social
service providers that place older women at a disadvantage when it comes to HIV
prevention, education, and treatment.
PMID- 25133950
TI - Acquired cutis laxa associated with heavy chain deposition disease involving
dermal elastic fibers.
AB - IMPORTANCE: Acquired cutis laxa is a rare cutaneous manifestation of hematologic
malignancy. We report a case of gamma heavy chain deposition disease (HCDD)
associated with acquired cutis laxa, renal involvement, and hypocomplementemia
and propose a mechanism of elastic fiber degradation in the skin of this patient
with HCDD. OBSERVATIONS: To determine the localization of immunoglobulin heavy
chains and complement activation in the skin of a patient with HCDD, we examined
her skin biopsy specimens under light and electron microscopy. Analysis
demonstrated the deposition of gamma heavy chain and complement components C1q
and C3 on the surfaces of dermal elastic fibers, indicating complement fixation
by the deposited heavy chains. Electron microscopy revealed finely granular
electron-dense deposits coating the surfaces of frayed dermal elastic fibers.
CONCLUSIONS AND RELEVANCE: The pathogenesis of cutis laxa in this condition is
poorly understood. We hypothesize a mechanism of elastic tissue destruction by
complement fixation with resultant activation of the complement cascade
ultimately causing elastolysis. Based on our findings and those of other reports,
we propose that skin heavy chain deposition can serve as a marker of plasma cell
secretory activity in HCDD, although further studies are needed.
PMID- 25133951
TI - Regioselective formal hydroamination of styrenes with 1-phenyl-1H-tetrazole-5
thiol.
AB - 1-Phenyl-1H-tetrazole-5-thiol 1 (PT-thiol) is employed in a unique Markovnikov
selective formal hydroamination of styrenyl compounds in the presence of
catalytic amounts of Ga(OTf)3. This gives rise to the formation of
tetrazolothione moieties in an atom-economical manner. Mechanistically, we have
determined that this transformation may occur by kinetically favored
hydrothiolation, followed by rearrangement to the observed hydroamination
products.
PMID- 25133953
TI - Microthermodynamic interpretation of fluid states from FTIR measurements in lipid
membranes: a Monte Carlo study.
AB - Fourier transform infrared spectroscopy (FTIR) is usually employed to obtain
transition temperatures of lipids and lipid mixtures and the effect on it of
several effectors, such as cholesterol. However, no interpretation of the
molecular information provided by the frequency shift to higher values observed
at Tc is available. In this article, we demonstrate that data obtained by means
of FTIR measurements contain information about the microscopic thermodynamics of
the lipid-phase transition. By means of Monte Carlo simulation, we have been able
to show that the frequency shift from low to high values can be taken as a two
state transition of molecular constituents in a lattice rearrangement. According
to the model, at temperatures below Tc all of the groups are defined in the
lowest-energy state defined by the lowest frequency value and therefore they are
all connected in a gel lattice. Above Tc, some groups may reach different energy
states depending on the restrictions imposed on the groups. Ideally, when all of
the groups are able to reach the highest frequency, a fully "fluid" state is
reached, which is a disordered state. If we take this hypothetical state as a
reference, it is possible to show that the higher states become less accessible.
The model is suitable for describing the effect of cholesterol, which is able to
dump the phase transition and is congruent with previous data denoting that in
the so-called fluid phase the first four to five methylene groups remain in the
gel state even above Tc. The frequency value attained above Tc depends on the
nature of the lipid acyl chain.
PMID- 25133954
TI - Polysaccharide-based networks from homogeneous chitosan-tripolyphosphate
hydrogels: synthesis and characterization.
AB - Polysaccharide networks, in the form of hydrogels and dried membranes based on
chitosan and on the cross-linker tripolyphosphate (TPP), were developed using a
novel approach. TPP was incorporated into chitosan by slow diffusion to favor a
controlled gelation. By varying chitosan, TPP, and NaCl concentration, transition
from inhomogeneous to homogeneous systems was achieved. Rheology and uniaxial
compression tests enabled to identify the best performing hydrogel composition
with respect to mechanical properties. FTIR, (31)P NMR, and spectrophotometric
methods were used to investigate the interaction chitosan-TPP, the kinetics of
phosphates diffusion during the dialysis and the amount of TPP in the hydrogel. A
freeze-drying procedure enabled the preparation of soft pliable membranes. The
lactate dehydrogenase assay demonstrated the biocompatibility of the membranes
toward fibroblasts. Overall, we devised a novel approach to prepare homogeneous
macroscopic chitosan/TPP-based biomaterials with tunable mechanical properties
and good biocompatibility that show good potential as novel polysaccharide
derivatives.
PMID- 25133955
TI - Dynamic observation of phase transformation behaviors in indium(III) selenide
nanowire based phase change memory.
AB - Phase change random access memory (PCRAM) has been extensively investigated for
its potential applications in next-generation nonvolatile memory. In this study,
indium(III) selenide (In2Se3) was selected due to its high resistivity ratio and
lower programming current. Au/In2Se3-nanowire/Au phase change memory devices were
fabricated and measured systematically in an in situ transmission electron
microscope to perform a RESET/SET process under pulsed and dc voltage swept mode,
respectively. During the switching, we observed the dynamic evolution of the
phase transformation process. The switching behavior resulted from
crystalline/amorphous change and revealed that a long pulse width would induce
the amorphous or polycrystalline state by different pulse amplitudes, supporting
the improvement of the writing speed, retention, and endurance of PCRAM.
PMID- 25133956
TI - Work zone safety analysis and modeling: a state-of-the-art review.
AB - OBJECTIVE: Work zone safety is one of the top priorities for transportation
agencies. In recent years, a considerable volume of research has sought to
determine work zone crash characteristics and causal factors. Unlike other non
work zone-related safety studies (on both crash frequency and severity), there
has not yet been a comprehensive review and assessment of methodological
approaches for work zone safety. To address this deficit, this article aims to
provide a comprehensive review of the existing extensive research efforts focused
on work zone crash-related analysis and modeling, in the hopes of providing
researchers and practitioners with a complete overview. METHODS: Relevant
literature published in the last 5 decades was retrieved from the National Work
Zone Crash Information Clearinghouse and the Transport Research International
Documentation database and other public digital libraries and search engines.
Both peer-reviewed publications and research reports were obtained. Each study
was carefully reviewed, and those that focused on either work zone crash data
analysis or work zone safety modeling were identified. The most relevant studies
are specifically examined and discussed in the article. RESULTS: The identified
studies were carefully synthesized to understand the state of knowledge on work
zone safety. Agreement and inconsistency regarding the characteristics of the
work zone crashes discussed in the descriptive studies were summarized. Progress
and issues about the current practices on work zone crash frequency and severity
modeling are also explored and discussed. The challenges facing work zone safety
research are then presented. CONCLUSIONS: The synthesis of the literature
suggests that the presence of a work zone is likely to increase the crash rate.
Crashes are not uniformly distributed within work zones and rear-end crashes are
the most prevalent type of crashes in work zones. There was no across-the-board
agreement among numerous papers reviewed on the relationship between work zone
crashes and other factors such as time, weather, victim severity, traffic control
devices, and facility types. Moreover, both work zone crash frequency and
severity models still rely on relatively simple modeling techniques and
approaches. In addition, work zone data limitations have caused a number of
challenges in analyzing and modeling work zone safety. Additional efforts on data
collection, developing a systematic data analysis framework, and using more
advanced modeling approaches are suggested as future research tasks.
PMID- 25133957
TI - The cyanide ligands of [FeFe] hydrogenase: pulse EPR studies of (13)C and (15)N
labeled H-cluster.
AB - The two cyanide ligands in the assembled cluster of [FeFe] hydrogenase originate
from exogenous l-tyrosine. Using selectively labeled tyrosine substrates, the
cyanides were isotopically labeled via a recently developed in vitro maturation
procedure allowing advanced electron paramagnetic resonance techniques to probe
the electronic structure of the catalytic core of the enzyme. The ratio of the
isotropic (13)C hyperfine interactions for the two CN(-) ligands-a reporter of
spin density on their respective coordinating iron ions-collapses from ~5.8 for
the Hox form of hydrogenase to <2 for the CO-inhibited form. Additionally, when
the maturation was carried out using [(15)N]-tyrosine, no features previously
ascribed to the nitrogen of the bridging dithiolate ligand were observed
suggesting that this bridge is not sourced from tyrosine.
PMID- 25133959
TI - Probing local strain at MX(2)-metal boundaries with surface plasmon-enhanced
Raman scattering.
AB - Interactions between metal and atomically thin two-dimensional (2D) materials can
exhibit interesting physical behaviors that are of both fundamental interests and
technological importance. In addition to forming a metal-semiconductor Schottky
junction that is critical for electrical transport, metal deposited on 2D layered
materials can also generate a local mechanical strain. We investigate the local
strain at the boundaries between metal (Ag, Au) nanoparticles and MX2 (M = Mo, W;
X = S) layers by exploiting the strong local field enhancement at the boundary in
surface plasmon-enhanced Raman scattering (SERS). We show that the local
mechanical strain splits both the in-plane vibration mode E2g(1) and the out-of
plane vibration mode A1g in monolayer MoS2, and activates the in-plane mode E1g
that is normally forbidden in backscattering Raman process. In comparison, the
effects of mechanical strain in thicker MoS2 layers are significantly weaker. We
also observe that photoluminescence from the indirect bandgap transition (when
the number of layers is >=2) is quenched with the metal deposition, while a
softened and broadened shoulder peak emerges close to the original direct-bandgap
transition because of the mechanical strain. The strain at metal-MX2 boundaries,
which locally modifies the electronic and phonon structures of MX2, can have
important effects on electrical transport through the metal-MX2 contact.
PMID- 25133960
TI - A new library of arsine, stibine-stabilized N-heterocyclic carbene palladium
complexes: synthesis, structures and activities in C-C and C-N coupling
reactions.
AB - A series of new N-heterocyclic carbene palladium complexes bearing AsPh3 and
SbPh3 functions PdCl2(IMes)(AsPh3) (1a), PdCl2(IMes)(SbPh3) (1b),
PdCl2(IPr)(AsPh3) (1c), PdCl2(IPr)(SbPh3) (1d), PdCl2(SIMes)(AsPh3) (2a),
PdCl2(SIMes)(SbPh3) (2b), PdCl2(SIPr)(AsPh3) (2c), and PdCl2(SIPr)(SbPh3) (2d)
(IMes = N,N'-bis-(2,4,6-trimethylphenyl)imidazol-2-ylidene; IPr = N,N'-bis-(2,6
di(iso-propyl)phenyl)imidazol-2-ylidene; SIMes = N,N'-bis-(2,4,6
trimethylphenyl)imidazolidin-2-ylidene; SIPr = N,N'-bis-(2,6-di(iso
propyl)phenyl)imidazolidin-2-ylidene) was synthesized and fully characterized by
(1)H NMR, (13)C NMR, and FT-IR spectroscopy, elemental analysis and single
crystal X-ray crystallography. The catalytic potential of these arsine and
stibine-stabilized carbene palladium complexes for Pd-mediated transformations
was investigated with various substrates in the Hiyama cross-coupling reactions
and Buchwald-Hartwig aminations. The results demonstrate that these complexes
show high catalytic activity and good tolerance to various chemical functions.
PMID- 25133958
TI - Exome sequencing in the clinical diagnosis of sporadic or familial cerebellar
ataxia.
AB - IMPORTANCE: Cerebellar ataxias are a diverse collection of neurologic disorders
with causes ranging from common acquired etiologies to rare genetic conditions.
Numerous genetic disorders have been associated with chronic progressive ataxia
and this consequently presents a diagnostic challenge for the clinician regarding
how to approach and prioritize genetic testing in patients with such clinically
heterogeneous phenotypes. Additionally, while the value of genetic testing in
early-onset and/or familial cases seems clear, many patients with ataxia present
sporadically with adult onset of symptoms and the contribution of genetic
variation to the phenotype of these patients has not yet been established.
OBJECTIVE: To investigate the contribution of genetic disease in a population of
patients with predominantly adult- and sporadic-onset cerebellar ataxia. DESIGN,
SETTING, AND PARTICIPANTS: We examined a consecutive series of 76 patients
presenting to a tertiary referral center for evaluation of chronic progressive
cerebellar ataxia. MAIN OUTCOMES AND MEASURES: Next-generation exome sequencing
coupled with comprehensive bioinformatic analysis, phenotypic analysis, and
clinical correlation. RESULTS: We identified clinically relevant genetic
information in more than 60% of patients studied (n = 46), including diagnostic
pathogenic gene variants in 21% (n = 16), a notable yield given the diverse
genetics and clinical heterogeneity of the cerebellar ataxias. CONCLUSIONS AND
RELEVANCE: This study demonstrated that clinical exome sequencing in patients
with adult-onset and sporadic presentations of ataxia is a high-yield test,
providing a definitive diagnosis in more than one-fifth of patients and
suggesting a potential diagnosis in more than one-third to guide additional
phenotyping and diagnostic evaluation. Therefore, clinical exome sequencing is an
appropriate consideration in the routine genetic evaluation of all patients
presenting with chronic progressive cerebellar ataxia.
PMID- 25133961
TI - Resource utilization and use of life-extending therapies and corticosteroids in
prostate cancer patients with corticosteroid-sensitive comorbidities.
AB - OBJECTIVES: Corticosteroids (CSs) are used concomitantly with life-extending
therapies (LETs) in patients with castration-resistant prostate cancer (CRPC).
This study examined time to LETs, LETs and concomitant CS adherence, and monthly
all-cause healthcare utilization and costs in patients with CPRC with and without
CS-sensitive comorbidities in the Veterans Health Administration population.
METHODS: Patients had CRPC if records showed prostate cancer diagnosis,
medical/surgical castration and >=2 prostate-specific antigen increases through 1
June 2007-31 May 2012. CS-sensitive comorbidities were assessed 6 months prior to
the index date. Adherence, defined as medication possession ratio (MPR) >=0.8,
among patients initiating LETs (cabazitaxel, docetaxel, or abiraterone acetate)
before 30 November 2011, resource utilization and costs among patients with
concomitant CS were assessed. Statistical analysis included descriptive, Cox
proportional hazards, and logistic regression models. RESULTS: Common CS
sensitive conditions among 12,128 patients with CRPC included hypertension
(75.74%) and hyperlipidemia (54.69%). Those with glaucoma (hazard ratio [HR] =
0.67), ischemic heart disease (HR = 0.78), and peripheral vascular disease (PVD)
(HR = 0.78) were less likely to be prescribed LETs (all p < 0.01). Duration of
LET was shorter among patients with CS-sensitive comorbidities (125.02 vs 133.08
days; p = 0.04) in the 6 month follow-up period. Among LET-treated patients with
and without CS-sensitive comorbidities, less than half had MPR >= 0.8 (LET:
48.72% vs 54.05%; concomitant CS: 42.19% vs 40.54%, respectively).
Cerebrovascular disease (odds ratio = 0.107; 95% confidence interval = 0.012 to
0.966) and PVD (odds ratio = 0.523; 95% confidence interval = 0.276 to 0.991)
were associated with reduced CS adherence. Among patients with concomitant CS,
those with CS-sensitive comorbidities had more inpatient stays than those without
(20.45% vs 12.88%; p = 0.033), incurring higher monthly inpatient costs ($1157 vs
$342; p < 0.0001) and total costs ($5725 vs $4772; p = 0.036). CONCLUSION: CS
sensitive conditions influence initiation and duration of LETs, concomitant CS
adherence, inpatient stays, and total costs. Future efforts should focus on
specific strategies for treating prostate cancer patients with CS-sensitive
comorbidities to ensure that they have appropriate access to LETs and to reduce
costs and inpatient stays. Study limitations include the use of retrospective
claims data and the relatively restricted subpopulation of older North American
males.
PMID- 25133962
TI - Acute postoperative pain relief with immediate-release tapentadol: randomized,
double-blind, placebo-controlled study conducted in South Korea.
AB - OBJECTIVE: To broaden the ethnic groups in which tapentadol IR is evaluated for
treating acute postoperative pain to include Asians. METHODS: In this phase 3,
multicenter, double-blind, randomized study, 352 Korean adults with moderate-to
severe pain following hallux valgus surgery received tapentadol IR 50 or 75 mg or
placebo orally every 4-6 hours for 72 hours. Patients requesting other (rescue)
analgesics during this period were discontinued for lack of efficacy. The primary
endpoint, sum of pain intensity difference (SPID) over 48 hours, was evaluated
based on the difference between tapentadol IR and placebo in least squares (LS)
mean change from baseline using analysis of covariance (ANCOVA). Secondary
endpoints included the time to first rescue medication use and the distribution
of responder rates. RESULTS: A treatment effect, favoring tapentadol IR, was
observed for SPID48 (p < 0.001 for both doses vs. placebo, ANCOVA). The between
group difference (vs. placebo) in LS means of SPID48 was 76.4 (95% CI: 51.0,
101.7) for tapentadol IR 50 mg and 90.6 (95% CI: 65.1, 116.1) for tapentadol IR
75 mg. Time to first rescue medication use was delayed for tapentadol IR (p <
0.001 for both doses vs. placebo; log-rank test). The distribution of responders
at 12, 24, 48, and 72 hours favored tapentadol IR (p <= 0.001 for both doses vs.
placebo; Cochran-Mantel-Haenszel test). Dizziness, nausea, and vomiting were each
reported in >= 10% tapentadol-treated patients and at an incidence >= 2-fold
higher vs. placebo. The study findings may be limited by study drug dosing every
4 to 6 hours and frequent monitoring during treatment, neither of which mimic
pain treatment in clinical practice. However, any potential bias based on this
systematic monitoring of patients would be mitigated by the randomized, double
blind nature of the study, with all treatment groups similarly affected by such
biases, if any. CONCLUSIONS: Tapentadol IR reduced acute pain intensity,
significantly more than placebo, after orthopedic surgery in Korean patients.
CLINICAL TRIAL REGISTRATION: NCT01516008.
PMID- 25133964
TI - The latest on optical coherence tomography.
PMID- 25133963
TI - Etoricoxib in the treatment of Korean patients with osteoarthritis in a double
blind, randomized controlled trial.
AB - OBJECTIVE: We evaluated the COX-2 inhibitors, etoricoxib and celecoxib, in Korean
patients with osteoarthritis (OA). METHODS: This study included patients (>= 40
years of age) with a clinical and radiographic diagnosis of knee OA. Patients
were randomized to etoricoxib 30 mg (qd) or celecoxib 200 mg (qd) in a 12 week
randomized, controlled, double-blind study. Prior NSAID users were to demonstrate
a worsening of symptoms upon withdrawal of medication. Efficacy endpoints
included the time-weighted average change from baseline in the WOMAC VA 3.0 Pain
Subscale (100 mm Visual Analog Scale [VAS]; primary endpoint), the WOMAC VA 3.0
Physical Function Subscale (100 mm VAS), and Patient Global Assessment of Disease
Status (PGAD) (100 mm VAS). The primary hypothesis was that etoricoxib 30 mg is
non-inferior to celecoxib 200 mg as assessed by the primary endpoint (the non
inferiority margin was set at 10 mm VAS). Adverse events (AEs), laboratory
parameters, and vital signs were monitored. RESULTS: There were 239 patients
(89.5% female; mean age: 63.3 years) randomized to etoricoxib 30 mg (n = 120) and
celecoxib 200 mg (n = 119). The differences (etoricoxib vs celecoxib) in least
square (LS) mean change (95% CI) for WOMAC Pain, WOMAC Physical Function, and
PGAD were -1.63 mm (-5.37, 2.10), -1.32 mm (-4.88, 2.23), and -1.09 mm (-5.48,
3.30), respectively. Drug-related clinical AEs occurred in 6.7% (etoricoxib) and
2.5% (celecoxib) of patients. This study was limited because it was not designed
or powered to adequately capture and evaluate rare AEs associated with NSAID
treatment. CONCLUSIONS: Etoricoxib 30 mg administered once daily in Korean
patients with knee OA demonstrated non-inferior clinical efficacy to celecoxib
200 mg over 12 weeks of treatment as assessed by all primary and secondary
outcomes. Etoricoxib 30 mg qd and celecoxib 200 mg qd were generally safe and
well tolerated. CLINICAL TRIAL REGISTRATION: NCT01554163.
PMID- 25133965
TI - Optical coherence tomography in papilledema: what am I missing?
AB - BACKGROUND: Grading of papilledema severity is subjective and based on monocular
fundus features of the optic nerve. Interobserver agreement on grading the
severity of papilledema is poor among expert observers, even using well-defined
criteria such as the Frisen scale, which is a non-continuous ordinal scale of
grading. Furthermore, non-expert clinicians often find it difficult to properly
view and interpret features of the optic nerve using ophthalmoscopy, which can
lead to failure to diagnose papilledema in non-ophthalmologic care settings. This
may delay treatment, which can result in vision loss. Distinguishing papilledema
from pseudopapilledema can also be difficult when surface drusen are not easily
identified. Once papilledema is diagnosed, it is often difficult to determine
whether a reduction in optic nerve edema is due solely to improvement in the
status of the nerve or whether this represents concomitant loss of axons and
viable retinal ganglion cells, leading to a poor visual outcome. Timely
advancement of treatment would occur if loss of neurons could be diagnosed at an
earlier stage of evaluation while optic disc edema is still present. This review
will critically assess the role of optical coherence tomography (OCT) in solving
these problems by providing an advanced imaging approach for diagnosis of
papilledema and evaluating its severity on a continuous scale and evaluating the
causes of visual loss in the setting of a swollen nerve. METHODS ACQUISITION: The
published literature (PubMed) was reviewed from 2000 to 2014 on the use of OCT
for diagnosing papilledema, differentiating it from pseudopapilledema, providing
a continuous scale of its severity and in evaluating causes of visual loss.
RESULTS: Recent evidence shows that OCT analysis of the retinal nerve fiber layer
and retinal ganglion cell layer in papilledema can be associated with misleading
artifacts due to layer segmentation failures. Newer 3D algorithms using
neighboring locations help to overcome these problems. Disc volume appears to be
a promising continuous measure of papilledema that is robust and has less
associated artifacts. Buried optic disc drusen can be identified using enhanced
depth OCT imaging, but recent studies have shown poor ability to differentiate
papilledema from pseudopapilledema using OCT when the degree of disc evaluation
is similar. Analysis of the retinal ganglion cell layer shows promise of early
detection of vision loss due to neuronal injury. Subretinal fluid is easily
identified with OCT and can help to identify a potentially reversible component
of vision loss. Newer OCT imaging methods will allow the definition of
capillaries and flow within them in and around the optic nerve head. CONCLUSIONS:
Currently, the most useful OCT derived features relevant to papilledema are disc
volume, subretinal fluid, buried disc drusen, and thickness of the retinal
ganglion cell layer.
PMID- 25133966
TI - Clinical trials to clinical use: using vision as a model for multiple sclerosis
and beyond.
AB - Optical coherence tomography (OCT) has made possible the structure-function
correlations that uniquely characterize the afferent visual pathway as a model
for understanding multiple sclerosis (MS) and for developing new treatments.
During the past decade, OCT measures of retinal nerve fiber layer (RNFL) and
ganglion cell/inner plexiform layer (GCL + IPL) thickness have evolved from being
a means to validate visual function tests, such as low-contrast letter acuity, to
provide a window on the axonal and neuronal loss that are now widely recognized
as contributors to permanent visual dysfunction in MS. Although acute optic
neuritis (ON) leads to thinning of the RNFL by 20%-40% within 3 months after a
single episode, thinning of the RNFL and GCL + IPL occur over time in MS eyes
even in the absence of an acute ON history. As such, OCT and its functional and
patient-reported correlates of low-contrast acuity and vision-specific quality of
life (QOL) have now been incorporated into MS clinical trials. Results of an
ongoing, phase 2 trial of a remyelinating agent that uses acute ON as a model for
assessing therapeutic efficacy will define even further the important role for
OCT in documenting structural changes as we move forward from clinical trials to
clinical use.
PMID- 25133967
TI - Retinal segmentation using multicolor laser imaging.
AB - Spectral-domain optical coherence tomography (SD-OCT) changed 3 worlds: clinical
care, clinical research, and the regulatory environment of phases 2, 3, and 4
pharmaceutical and surgical trials. OCT is now undergoing another transformation
with multicolor technology, which acquires images using data from 3 simultaneous
lasers: red, green, and blue, taking advantage of the different wavelengths of
each of these colors to most precisely image 3 different zones of the retina.
Rather than seeing only the surface of the retina and optic disc and any large
lesions in the deeper retina, this technology provides a topographic map of the
outer (red), mid (green), and inner (blue) retina somewhat similar to what is
observed with fundus autoflourescence of deep retina, retinal pigment epithelium,
and choroid. Multicolor imaging will supplement and help to define what is
observed with traditional fundus photography and SD-OCT. In addition, it may
demonstrate abnormalities when routine photography is normal and when SD-OCT
findings are equivocal. This review will illustrate the basic principles of
multicolor imaging and will show clinical examples of how this technique can
further define retinal and optic nerve pathology.
PMID- 25133968
TI - Optical coherence tomography technologies: which machine do you want to own?
AB - Optical coherence tomography (OCT) has evolved over the past decade to become one
of the most important ancillary tests in ophthalmic practice. This noninvasive
ocular imaging technique provides high-resolution, cross-sectional images of the
retinal nerve fiber layer (RNFL), macular region, ganglion cell layer, and optic
nerve head. With OCT, we can learn much about axonal-neuronal integrity in the
anterior aspect of the afferent visual pathway and gain insights about mechanisms
of brain injury in various central nervous system disorders.
PMID- 25133969
TI - Liver agenesis with omphalocele: a report of two human embryos using serial
histological sections.
AB - We identified 2 human embryos, with crown-rump lengths (CRLs) of 22 mm and 23 mm
and a gestational age of approximately 7 weeks (O'Rahilly's stage 21-22), with
liver agenesis and omphalocele. Serial histological sections were prepared of the
entire body of one specimen, whereas sections of the neck, including the upper
part of the heart, were missed for the other specimen as a result of tissue
damage during the abortion. In addition, isolated omphalocele was assessed in
another embryo (CRL = 25 mm) for comparison with atypical omphalocele in the
embryos with liver agenesis. The 2 embryos with liver agenesis were characterized
by (1) the absence of the anterior part of the diaphragm; (2) abnormality in the
venous pole of the heart; (3) a normal stomach in the left upper abdominal
cavity; and (4) normal pancreas development with normal midgut rotation. The most
likely cause of liver agenesis, when combined with isolated omphalocele, was a
defect in the anterior extension or migration of the septum transversum rather
than a mechanical separation of the hepatic diverticulum from the septum
transversum.
PMID- 25133971
TI - Core-shell nanoparticle-based peptide therapeutics and combined hyperthermia for
enhanced cancer cell apoptosis.
AB - Mitochondria-targeting peptides have garnered immense interest as potential
chemotherapeutics in recent years. However, there is a clear need to develop
strategies to overcome the critical limitations of peptides, such as poor
solubility and the lack of target specificity, which impede their clinical
applications. To this end, we report magnetic core-shell nanoparticle (MCNP)
mediated delivery of a mitochondria-targeting pro-apoptotic amphipathic tail
anchoring peptide (ATAP) to malignant brain and metastatic breast cancer cells.
Conjugation of ATAP to the MCNPs significantly enhanced the chemotherapeutic
efficacy of ATAP, while the presence of targeting ligands afforded selective
delivery to cancer cells. Induction of MCNP-mediated hyperthermia further
potentiated the efficacy of ATAP. In summary, a combination of MCNP-mediated ATAP
delivery and subsequent hyperthermia resulted in an enhanced effect on
mitochondrial dysfunction, thus resulting in increased cancer cell apoptosis.
PMID- 25133972
TI - Silymarin inhibits the progression of fibrosis in the early stages of liver
injury in CCl4-treated rats.
AB - Liver fibrosis, a common condition occurring during the evolution of almost all
chronic liver diseases, is the consequence of hepatocyte injury that leads to the
activation of Kupffer cells and hepatic stellate cells (HSC). Silymarin (Si) is a
herbal product widely used for its hepatoprotective potential. Our study aims to
investigate the effects of two different doses of Silymarin on a CCl4-induced
model of liver fibrosis with a focus on the early stages of liver injury. Fifty
Wistar rats were randomly divided into five groups (n=10): control group
(sunflower oil twice a week); CMC group (carboxymethyl cellulose five times a
week, sunflower oil twice a week); CCl4 group (CCl4 in sunflower oil, by gavage,
twice a week); CCl4+Si 50 group (CCl4 twice a week, Silymarin 50 mg/b.w. in CMC
five times a week); and CCl4+Si 200 group (similar to the previous group, with Si
200 mg/b.w.). One month after the experiment began we explored hepato-cytolysis
(aminotransferases and lactate dehydrogenase), oxidative stress, fibrosis
(histological score, hyaluronic acid), markers of HSC activation (transforming
growth factor beta1 [TGF-beta1], and alpha-smooth muscle actin [alpha-SMA]
expression by western blot) and activation of Kupffer cells by
immunohistochemistry. Our data showed that Si 50 mg/b.w. had the capacity of
reducing oxidative stress, hepato-cytolysis, fibrosis, activation of Kupffer
cells, and the expression of alpha-SMA and TGF-beta1 with better results than Si
200 mg/b.w. Thus, the usual therapeutic dose of Silymarin, administered in the
early stages of fibrotic changes is capable of inhibiting the fibrogenetic
mechanism and the progression of initial liver fibrosis.
PMID- 25133975
TI - A highly enantioselective hydrogenation of silyl enol ethers catalyzed by chiral
frustrated Lewis pairs.
AB - Using a simple combination of tri-tert-butylphosphine and chiral borane generated
in situ by the hydroboration of chiral diene with HB(C6F5)2 as a frustrated Lewis
pair catalyst, a highly enantioselective metal-free hydrogenation of silyl enol
ethers was successfully realized to furnish a variety of optically active
secondary alcohols in 93-99% yields with 88->99% ee's.
PMID- 25133976
TI - Elucidating the ring inversion mechanism(s) for biscalixarenes.
AB - Biscalix[4]arene can be constructed from a calix[4]arene by substitution of a
methylene bridge hydrogen by another equivalent moiety. The use of
biscalix[4]arenes (biscal) as precursors for the creation of new polymetallic
clusters such as single-molecule magnets has potential in the fields of data
storage and other applications. Polymetallic clusters involving biscal are
expected to preferentially involve octadentate binding to two metal centers (one
metal center per tetraphenolic pocket), requiring full inversion of one of the
annular rings. In this work, we use density functional theory to establish the
mechanism behind this process, considering the various energy pathways and
providing insight into the preferred route to full and partial inversion.
Fourteen possible pathways to full inversion are presented, including all
transition states (up to seven per pathway). Subsequently, the lowest energy
pathway to full inversion was found to have a barrier height of 19.31 kcal mol(
1). Solvent optimizations using PCM (with and without SMD) and CPCM solvent
models suggest long-range solvent effects may be relatively unimportant in the
inversion process. This study represents the first use of density functional
theory to elucidate the entire potential energy surface, including barrier
heights, of the ring inversion process of biscalix[4]arenes.
PMID- 25133974
TI - Spectacle correction versus no spectacles for prevention of strabismus in
hyperopic children.
AB - BACKGROUND: Hyperopia (far-sightedness) in infancy requires accommodative effort
to bring images into focus. Prolonged accommodative effort has been associated
with an increased risk of strabismus (eye misalignment). Strabismus makes it
difficult for the eyes to work together and may result in symptoms of asthenopia
(eye strain) and intermittent diplopia (double vision), and makes near work tasks
difficult to complete. Untreated strabismus may result in the development of
amblyopia (lazy eye). The prescription of spectacles to correct hyperopic
refractive error is believed to prevent the development of strabismus.
OBJECTIVES: To assess the effectiveness of prescription spectacles compared with
no intervention for the prevention of strabismus in infants and children with
hyperopia. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes
and Vision Group Trials Register) (2014, Issue 4), Ovid MEDLINE, Ovid MEDLINE In
Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE
(January 1946 to April 2014), EMBASE (January 1980 to April 2014), PubMed (1966
to April 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled
trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health
Organization (WHO) International Clinical Trials Registry Platform (ICTRP)
(www.who.int/ictrp/search/en). We did not use any date or language restrictions
in the electronic searches for trials. We last searched the electronic databases
on 3 April 2014. We also searched the Science Citation Index database in
September 2013. SELECTION CRITERIA: We included randomized controlled trials and
quasi-randomized trials investigating the assignment to spectacle intervention or
no treatment for children with hyperopia. The definition of hyperopia remains
subjective, but we required it to be at least greater than +2.00 diopters (D) of
hyperopia. DATA COLLECTION AND ANALYSIS: Two review authors independently
extracted data using the standard methodologic procedures expected by The
Cochrane Collaboration. One review author entered data into Review Manager and a
second review author verified the data entered. The two review authors resolved
discrepancies at all stages of the review process. MAIN RESULTS: We identified
three randomized controlled trials (855 children enrolled) in this review. These
trials were all conducted in the UK with follow-up periods ranging from one to
3.5 years. We judged the included studies to be at high risk of bias, due to use
of quasi-random methods for assigning children to treatment, no masking of
outcomes assessors, and high proportions of drop-outs. None of the three trials
accounted for missing data and analyses were limited to the available-case data
(674 (79%) of 855 children enrolled for the primary outcome). These factors
impair our ability to assess the effectiveness of treatment.Analyses
incorporating the three trials we identified in this review (674 children)
suggested the effect of spectacle correction initiated prior to the age of one
year in hyperopic children between three and four years of age is uncertain with
respect to preventing strabismus (risk ratio (RR) 0.71; 95% confidence interval
(CI) 0.44 to 1.15; very low quality evidence). Based on a meta-analysis of three
trials (664 children), the risk of having visual acuity worse than 20/30 at three
years of age was also uncertain for children with spectacles compared with those
without spectacle correction irrespective of compliance (RR 0.87; 95% CI 0.60 to
1.26; very low quality evidence).Emmetropization was reported in two trials: one
trial suggested that spectacles impede emmetropization, and the second trial
reported no difference in the rate of refractive error change. AUTHORS'
CONCLUSIONS: Although children who were allocated to the spectacle group were
less likely to develop strabismus and less likely to have visual acuity worse
than 20/30 children allocated to no spectacles, these effects may have been
chance findings, or due to bias. Due to the high risk of bias and poor reporting
of included trials, the true effect of spectacle correction for hyperopia on
strabismus is still uncertain.
PMID- 25133977
TI - Reward dependence moderates smoking-cue- and stress-induced cigarette cravings.
AB - BACKGROUND: Cigarette cravings following exposure to smoking cues in a smoker's
environment are thought to play an important role in cessation failure. The
possibility that dispositional factors may impact cue-induced cravings, though
intriguing, has received little attention. According to Cloninger's
Tridimensional Personality Theory, factors such as reward dependence (RD), harm
avoidance (HA), and novelty seeking (NS) may figure prominently in risk for
addiction, as well as relapse, in individuals attempting to abstain from drug and
alcohol use. Particularly interesting in this regard is the possibility that
smokers with higher levels of RD, who are especially sensitive to reward signals,
will have heightened craving reactions to smoking cues. METHODS: To that end, non
treatment-seeking nicotine dependent smokers (n=96, mean age=41.1, 47% African
American, 17% Caucasian, 22% Hispanic, 19.3cigs/day, FTND=7.5) underwent a
classic experimental cue-induction, during which they were exposed to imagery of:
(1) smoking, (2) neutral, and (3) stress cues, and reported their cigarette
cravings (0-100) before and after each exposure. Participants also completed the
Tridimensional Personality Questionnaire. RESULTS: Not surprisingly, smoking and
stress cues (but not neutral cues) elicited significant elevations in craving
(p's<0.0001). Consistent with study hypothesis, smokers who scored higher on RD
had stronger craving reactions to both smoking cues (p<.02) and stress cues
(p<.03). CONCLUSIONS: Findings raise the possibility that dispositional
characteristics, in particular, reward dependence, influence smoking by
potentiating reactions to environmental smoking cues. Furthermore, the similar
effects of RD on stress-induced craving suggest that both cue-and stress-induced
cravings may be influenced by a common underlying disposition.
PMID- 25133978
TI - The relationship between perceived stress and cue sensitivity for alcohol.
AB - Previous research has shown that cue sensitivity and stress affect the risk for
relapse in alcohol-dependent patients. Theoretically, a link between the two can
be expected. However, a clear overview of the interplay of these factors is not
yet available. The purpose of this review was to examine the empirical evidence
for the influence of stress on sensitivity for alcohol-related cues. Empirical
studies indexed in PubMed, EMBASE, PsycINFO, and Web of Knowledge that assessed
the relation between stress and sensitivity for alcohol-related cues using
subjective, behavioral and/or physiological measures were included in the review.
Of the 359 articles screened, 12 were included in the review. Nine articles
supported the existence of the relationship between stress and heightened cue
sensitivity for alcohol-related cues, whereas three articles did not support our
hypothesis. We conclude that the relationship between stress and sensitivity to
alcohol cues appears to exist. In fact, there may be different factors at play:
our review points toward (1) differences between the effect of psychological
stress and physiological stress on cue-sensitivity, and (2) individual
differences regarding coping drinking which may explain stress-induced cues
sensitivity.
PMID- 25133979
TI - Magnetic relaxations arising from spin-phonon interactions in the nonthermally
activated temperature range for a double-decker terbium phthalocyanine single
molecule magnet.
AB - Magnetic relaxations arising from spin-phonon interactions for a magnetically
diluted double-decker terbium phthalocyanine single molecule magnet, dil1, in the
nonthermally activated temperature range have been investigated. While the
relaxation time, tau, is independent of the external static magnetic field,
H(dc), in the high temperature range, where linear relationships between -ln tau
and T(-1) are observed in the Arrhenius plot, magnetic field dependences for tau
are observed in the lower temperature range. The tau(-1) vs H(dc) plot at 12 K
fits the quadric curve when H(dc) < 12 kOe, while linear relationships are
observed in the tau(-1) vs T plots in the temperature range of 12-20 K. These
results indicate that the direct process is the dominant magnetic relaxation
pathway in the nonthermally activated temperature range, while the contribution
from the Raman process, if any, is not observable. We emphasize in this paper
that the contribution from the thermal relaxation processes and the quantum
tunneling of magnetizations (QTMs) to the experimentally observed magnetic
relaxations must be evaluated carefully in order to avoid confusion between the
thermal and quantum-mechanical relaxation pathways.
PMID- 25133973
TI - Nuclear cytoplasmic trafficking of proteins is a major response of human
fibroblasts to oxidative stress.
AB - We have used a subcellular spatial razor approach based on LC-MS/MS-based
proteomics with SILAC isotope labeling to determine changes in protein abundances
in the nuclear and cytoplasmic compartments of human IMR90 fibroblasts subjected
to mild oxidative stress. We show that response to mild tert-butyl hydrogen
peroxide treatment includes redistribution between the nucleus and cytoplasm of
numerous proteins not previously associated with oxidative stress. The 121
proteins with the most significant changes encompass proteins with known
functions in a wide variety of subcellular locations and of cellular functional
processes (transcription, signal transduction, autophagy, iron metabolism, TCA
cycle, ATP synthesis) and are consistent with functional networks that are
spatially dispersed across the cell. Both nuclear respiratory factor 2 and the
proline regulatory axis appear to contribute to the cellular metabolic response.
Proteins involved in iron metabolism or with iron/heme as a cofactor as well as
mitochondrial proteins are prominent in the response. Evidence suggesting that
nuclear import/export and vesicle-mediated protein transport contribute to the
cellular response was obtained. We suggest that measurements of global changes in
total cellular protein abundances need to be complemented with measurements of
the dynamic subcellular spatial redistribution of proteins to obtain
comprehensive pictures of cellular function.
PMID- 25133980
TI - Advanced thermopower wave in novel ZnO nanostructures/fuel composite.
AB - Thermopower wave is a new concept of energy conversion from chemical to thermal
to electrical energy, produced from the chemical reaction in well-designed hybrid
structures between nanomaterials and combustible fuels. The enhancement and
optimization of energy generation is essential to make it useful for future
applications. In this study, we demonstrate that simple solution-based
synthesized zinc oxide (ZnO) nanostructures, such as nanorods and nanoparticles
are capable of generating high output voltage from thermopower waves. In
particular, an astonishing improvement in the output voltage (up to 3 V; average
2.3 V) was achieved in a ZnO nanorods-based composite film with a solid fuel
(collodion, 5% nitrocellulose), which generated an exothermic chemical reaction.
Detailed analyses of thermopower waves in ZnO nanorods- and cube-like
nanoparticles-based hybrid composites have been reported in which nanostructures,
output voltage profile, wave propagation velocities, and surface temperature have
been characterized. The average combustion velocities for a ZnO nanorods/fuel and
a ZnO cube-like nanoparticles/fuel composites were 40.3 and 30.0 mm/s, while the
average output voltages for these composites were 2.3 and 1.73 V. The high output
voltage was attributed to the amplified temperature in intermixed composite of
ZnO nanostructures and fuel due to the confined diffusive heat transfer in
nanostructures. Moreover, the extended interfacial areas between ZnO nanorods and
fuel induced large amplification in the dynamic change of the chemical potential,
and it resulted in the enhanced output voltage. The differences of reaction
velocity and the output voltage between ZnO nanorods- and ZnO cube-like
nanoparticles-based composites were attributed to variations in electron mobility
and grain boundary, as well as thermal conductivities of ZnO nanorods and
particles. Understanding this astonishing increase and the variation of the
output voltage and reaction velocity, precise ZnO nanostructures, will help in
formulating specific strategies for obtaining enhanced energy generation from
thermopower waves.
PMID- 25133981
TI - Effects of holmium laser enucleation of the prostate on sexual function.
AB - OBJECTIVE: To evaluate the effects of holmium laser enucleation of the prostate
(HoLEP) on sexual function. METHODS: A retrospective analysis of 202 sexually
active patients who underwent HoLEP was performed. Patients were assessed at
baseline and 3 and 12 months post-HoLEP. Evaluations included uroflowmetry and
symptom questionnaires (five-item version of the International Index of Erectile
Function [IIEF-5], ICIQ-male sexual matters associated with LUTS [ICIQ-MLUTSsex],
American Urological Association symptom score [AUA-SS], and single-question
quality of life [QoL] score). Nonparametric, Fisher's exact, and chi-squared
tests were used to assess changes from baseline and to identify risk factors, if
any, associated with deterioration of sexual function after surgery. RESULTS: No
significant differences were found between the preoperative and postoperative
scores on the questionnaires that evaluated erection quality. However, 6.9% and
12.4% of the patients reported an increase or a reduction, respectively, of
greater than five points in total IIEF-5 score. The reduction in IIEF-5 score was
statistically significant only in the subgroup of patients without preoperative
erectile dysfunction (ED). No preoperative characteristics and no parameters
related to the surgery or postoperative outcome were significantly associated
with the impairment of erection quality after surgery. In fact, neither capsular
perforation nor the total laser energy used during the procedure affected
erections. Loss of antegrade ejaculation was found in 70.3% of patients, while
21% reported a reduction in semen quantity. However, concern regarding ED or
ejaculatory dysfunctions decreased with surgery. CONCLUSIONS: Although erectile
function was not altered in the vast majority of patients after HoLEP, patients
without preoperative ED displayed a relatively small, but still significant,
negative effect on erections. The overwhelming majority of patients suffered from
retrograde ejaculation after surgery.
PMID- 25133982
TI - Optimizing health for persons with multiple chronic conditions.
PMID- 25133984
TI - Single Entry Communities Increase Trip Distance and May Overestimate Neighborhood
Walkability.
AB - BACKGROUND: Neighborhood walkability is being promoted as an important factor in
public health efforts to decrease rates of physical inactivity. Single entry
communities (SEC), communities with only 1 entrance/exit, may result in an over
estimation of walkability. This design makes direct walking routes outside the
community nearly impossible and results in increased trip distance. The purpose
of this study was to determine if accounting for SECs resulted in a significant
difference in street connectivity. METHODS: Twenty geographically different Las
Vegas neighborhoods were chosen and the number of true intersections measured in
ArcGIS. Neighborhoods were then assessed for the presence of SECs using google
maps, ArcGIS land imagery, and field observation. Intersections inside SECs were
removed. A paired t test was used to assess the mean difference of intersection
density before and after adjustment. RESULTS: There was a statistically
significant decrease in the number of true intersections after the adjustment
(before mean = 57.8; after mean = 45.7). The eta squared statistic indicates a
large effect size (0.3). CONCLUSIONS: Single entry communities result in an over
estimation of street connectivity. If SECs are not accounted for, trip distances
will be underestimated and public health efforts to promote walking through
walkable neighborhoods may prove less effective.
PMID- 25133983
TI - Concerted bioinformatic analysis of the genome-scale blood transcription factor
compendium reveals new control mechanisms.
AB - Transcription factors play a key role in the development of a disease. ChIP
sequencing has become a preferred technique to investigate genome-wide binding
patterns of transcription factors in vivo. Although this technology has led to
many important discoveries, the rapidly increasing number of publicly available
ChIP-sequencing datasets still remains a largely unexplored resource. Using a
compendium of 144 publicly available murine ChIP-sequencing datasets in blood, we
show that systematic bioinformatic analysis can unravel diverse aspects of
transcription regulation; from genome-wide binding preferences, finding
regulatory partners and assembling regulatory complexes, to identifying novel
functions of transcription factors and investigating transcription dynamics
during development.
PMID- 25133985
TI - Identification of the halogenated compounds resulting from the 1997 Plastimet
Inc. fire in Hamilton, Ontario, using comprehensive two-dimensional gas
chromatography and (ultra)high resolution mass spectrometry.
AB - Between July 9-12, 1997, at least 400 tonnes of polyvinyl chloride (PVC) were
consumed in a fire at the Plastimet Inc. plastics recycling facility in Hamilton,
Ontario, Canada. This led to the release of contaminants, including highly toxic
polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF). This study re
examines a composite soil sample collected shortly after the fire using state-of
the-art FT-ICR (Fourier transform ion cyclotron resonance) and GC * GC-TOF
(comprehensive two-dimensional gas chromatography-time-of-flight) mass
spectrometry. The FT-ICR experiments led to the identification of approximately
150 molecular formulas, corresponding to chlorinated and mixed chloro/bromo
compounds. The majority of these are halogenated polycyclic aromatic hydrocarbons
(halo-PAHs), including highly substituted (e.g., C14HCl9 and C16HCl9) and high
molecular weight (e.g., C28H12Cl4) Cl-PAHs that have not been reported previously
in environmental samples. Complementary GC * GC-TOF experiments resolved
individual halo-PAHs, some of which were confirmed with available standards. The
concentrations of the most abundant halo-PAH groups, C14H8Cl2 (22 MUg/g) and
C16H8Cl2 (20 MUg/g) are much higher than reported dioxin values and comparable to
the corresponding PAH groups C14H10 (12 MUg/g) and C16H10 (19 MUg/g). The high
abundance of the halo-PAHs identified in this study highlights the need for
further investigation into their environmental occurrence and risk.
PMID- 25133987
TI - Seeking proxies for internal states in obsessive-compulsive disorder.
AB - Pervasive doubts are a central feature of obsessive-compulsive disorder (OCD). We
have theorized that obsessive doubts can arise in relation to any internal state
and lead to compensatory reliance on more discernible substitutes (proxies),
including rules and rituals. Previous findings corroborated this hypothesis, but
were based on students with high and low OCD tendencies and did not control for
anxiety. The present study tested our hypothesis in OCD participants using both
anxiety disorders and nonclinical controls. Twenty OCD participants, 20 anxiety
disorders participants, and 20 nonclinical participants underwent 2 experimental
procedures. In the first, participants had to produce specific levels of muscle
tension with and without the aid of biofeedback. In the second, participants were
asked to subjectively assess their own muscle tension after viewing preprogrammed
false feedback showing either increasing or decreasing levels of muscle tension.
As predicted, OCD participants were less accurate than anxiety disorder and
nonclinical participants in producing designated levels of muscle tension when
biofeedback was not available and more likely to request the biofeedback when
given the opportunity to do so. In the false feedback procedure, OCD participants
were more influenced by the false biofeedback when judging their own level of
muscle tension compared with the 2 controls groups. In both procedures, anxiety
disorder participants did not differ from the nonclinical controls. These results
support the hypothesis that individuals with OCD have attenuated access to and
reduced confidence in their internal states, and that this deficit is specific to
OCD and not attributable to anxiety.
PMID- 25133986
TI - Do people with schizophrenia have difficulty anticipating pleasure, engaging in
effortful behavior, or both?
AB - Motivation deficits are common in schizophrenia, but little is known about
underlying mechanisms, or the specific goals that people with schizophrenia set
in daily life. Using neurobiological heuristics of pleasure anticipation and
effort assessment, we examined the quality of activities and goals of 47 people
with and 41 people without schizophrenia, utilizing ecological momentary
assessment. Participants were provided cell phones and called 4 times a day for 7
days, and were asked about their current activities and anticipation of upcoming
goals. Activities and goals were later coded by independent raters on pleasure
and effort. In line with recent laboratory findings on effort computation
deficits in schizophrenia, relative to healthy participants, people with
schizophrenia reported engaging in less effortful activities and setting less
effortful goals, which were related to patient functioning. In addition, patients
showed some inaccuracy in estimating how difficult an effortful goal would be,
which in turn was associated with lower neurocognition. In contrast to previous
research, people with schizophrenia engaged in activities and set goals that were
more pleasure-based, and anticipated goals as being more pleasurable than
controls. Thus, this study provided evidence for difficulty with effortful
behavior and not anticipation of pleasure. These findings may have psychosocial
treatment implications, focusing on effort assessment or effort expenditure. For
example, to help people with schizophrenia engage in more meaningful goal
pursuits, treatment providers may leverage low-effort pleasurable goals by
helping patients to break down larger, more complex goals into smaller, lower
effort steps that are associated with specific pleasurable rewards.
PMID- 25133988
TI - Single water entropy: hydrophobic crossover and application to drug binding.
AB - Entropy of water plays an important role in both chemical and biological
processes e.g. hydrophobic effect, molecular recognition etc. Here we use a new
approach to calculate translational and rotational entropy of the individual
water molecules around different hydrophobic and charged solutes. We show that
for small hydrophobic solutes, the translational and rotational entropies of each
water molecule increase as a function of its distance from the solute reaching
finally to a constant bulk value. As the size of the solute increases (0.746 nm),
the behavior of the translational entropy is opposite; water molecules closest to
the solute have higher entropy that reduces with distance from the solute. This
indicates that there is a crossover in translational entropy of water molecules
around hydrophobic solutes from negative to positive values as the size of the
solute is increased. Rotational entropy of water molecules around hydrophobic
solutes for all sizes increases with distance from the solute, indicating the
absence of crossover in rotational entropy. This makes the crossover in total
entropy (translation + rotation) of water molecule happen at much larger size
(>1.5 nm) for hydrophobic solutes. Translational entropy of single water molecule
scales logarithmically (Str(QH) = C + kB ln V), with the volume V obtained from
the ellipsoid of inertia. We further discuss the origin of higher entropy of
water around water and show the possibility of recovering the entropy loss of
some hypothetical solutes. The results obtained are helpful to understand water
entropy behavior around various hydrophobic and charged environments within
biomolecules. Finally, we show how our approach can be used to calculate the
entropy of the individual water molecules in a protein cavity that may be
replaced during ligand binding.
PMID- 25133989
TI - One-step electrodeposited nickel cobalt sulfide nanosheet arrays for high
performance asymmetric supercapacitors.
AB - A facile one-step electrodeposition method is developed to prepare ternary nickel
cobalt sulfide interconnected nanosheet arrays on conductive carbon substrates as
electrodes for supercapacitors, resulting in exceptional energy storage
performance. Taking advantages of the highly conductive, mesoporous nature of the
nanosheets and open framework of the three-dimensional nanoarchitectures, the
ternary sulfide electrodes exhibit high specific capacitance (1418 F g(-1) at 5 A
g(-1) and 1285 F g(-1) at 100 A g(-1)) with excellent rate capability. An
asymmetric supercapacitor fabricated by the ternary sulfide nanosheet arrays as
positive electrode and porous graphene film as negative electrode demonstrates
outstanding electrochemical performance for practical energy storage
applications. Our asymmetric supercapacitors show a high energy density of 60 Wh
kg(-1) at a power density of 1.8 kW kg(-1). Even when charging the cell within
4.5 s, the energy density is still as high as 33 Wh kg(-1) at an outstanding
power density of 28.8 kW kg(-1) with robust long-term cycling stability up to
50,000 cycles.
PMID- 25133990
TI - From micelles to fibers: balancing self-assembling and random coiling domains in
pH-responsive silk-collagen-like protein-based polymers.
AB - We study the self-assembly of genetically engineered protein-based triblock
copolymers consisting of a central pH-responsive silk-like middle block (S(H)n,
where S(H) is a silk-like octapeptide, (GA)3GH and n is the number of repeats)
flanked by hydrophilic random coil outer blocks (C2). Our previous work has
already shown that triblocks with very long midblocks (n = 48) self-assemble into
long, stiff protein filaments at pH values where the middle blocks are uncharged.
Here we investigate the self-assembly behavior of the triblock copolymers for a
range of midblock lengths, n = 8, 16, 24, 48. Upon charge neutralization of S(H)n
by adjusting the pH, we find that C2S(H)8C2 and C2S(H)16C2 form spherical
micelles, whereas both C2S(H)24C2 and C2S(H)48C2 form protein filaments with a
characteristic beta-roll secondary structure of the silk midblocks. Hydrogels
formed by C2S(H)48C2 are much stronger and form much faster than those formed by
C2S(H)24C2. Enzymatic digestion of much of the hydrophilic outer blocks is used
to show that with much of the hydrophilic outer blocks removed, all silk
midblocks are capable of self-assembling into stiff protein filaments. In that
case, reduction of the steric repulsion by the hydrophilic outer blocks also
leads to extensive fiber bundling. Our results highlight the opposing roles of
the hydrophilic outer blocks and central silk-like midblocks in driving protein
filament formation. They provide crucial information for future designs of
triblock protein-based polymers that form stiff filaments with controlled
bundling, that could mimick properties of collagen in the extracellular matrix.
PMID- 25133991
TI - Modulated protonation of side chain aminoethylene repeats in N-substituted
polyaspartamides promotes mRNA transfection.
AB - Fine-tuning of chemical structures of polycation-based carriers (polyplexes) is
an attractive strategy for safe and efficient mRNA transfaction. Here, mRNA
polyplexes comprising N-substituted polyaspartamides with varied numbers of side
chain aminoethylene repeats were constructed, and their transfection ability
against human hepatoma cells was examined. Transfection efficacy clearly
correlated with the number of aminoethylene repeats: polyplexes with odd number
repeats (PA-Os) produced sustained increases in mRNA expression compared with
those with even number repeats (PA-Es). This predominant efficacy of PA-Os over
PA-Es was contradictory to our previous findings for pDNA polyplexes prepared
from the same N-substituted polyaspartamides, that is, PA-Es revealed superior
transfection efficacy of pDNA than PA-Os. Intracellular FRET analysis using flow
cytometry and polyplex tracking under confocal laser scanning microscopy revealed
that overall transfection efficacy was determined through the balance between
endosomal escaping capability and stability of translocated mRNA in cytoplasm. PA
Es efficiently transported mRNA into the cytoplasm. However, their poor
cytoplasmic stability led to facile degradation of mRNA, resulting in a less
durable pattern of transfection. Alternatively, PA-Os with limited capability of
endosomal escape eventually protect mRNA in the cytoplasm to induce sustainable
mRNA expression. Higher cytoplasmic stability of pDNA compared to mRNA may shift
the limiting step in transfection from cytoplasmic stability to endosomal escape
capacity, thereby giving an opposite odd-even effect in transfection efficacy.
Endosomal escaping capability and nuclease stability of polyplexes are correlated
with the modulated protonation behavior in aminoethylene repeats responding to
pH, appealing the substantial importance of chemistry to design polycation
structures for promoted mRNA transfection.
PMID- 25133993
TI - Pancreatic neoplasm with metastatic workup.
PMID- 25133992
TI - High-speed single-particle tracking of GM1 in model membranes reveals anomalous
diffusion due to interleaflet coupling and molecular pinning.
AB - The biological functions of the cell membrane are influenced by the mobility of
its constituents, which are thought to be strongly affected by nanoscale
structure and organization. Interactions with the actin cytoskeleton have been
proposed as a potential mechanism with the control of mobility imparted through
transmembrane "pickets" or GPI-anchored lipid nanodomains. This hypothesis is
based on observations of molecular mobility using various methods, although many
of these lack the spatiotemporal resolution required to fully capture all the
details of the interaction dynamics. In addition, the validity of certain
experimental approaches, particularly single-particle tracking, has been
questioned due to a number of potential experimental artifacts. Here, we use
interferometric scattering microscopy to track molecules labeled with 20-40 nm
scattering gold beads with simultaneous <2 nm spatial and 20 MUs temporal
precision to investigate the existence and mechanistic origin of anomalous
diffusion in bilayer membranes. We use supported lipid bilayers as a model system
and demonstrate that the label does not influence time-dependent diffusion in the
small particle limit (<=40 nm). By tracking the motion of the ganglioside lipid
GM1 bound to the cholera toxin B subunit for different substrates and lipid tail
properties, we show that molecular pinning and interleaflet coupling between
lipid tail domains on a nanoscopic scale suffice to induce transient
immobilization and thereby anomalous subdiffusion on the millisecond time scale.
PMID- 25133994
TI - Protective effects of clovamide against H2O2-induced stress in rat
cardiomyoblasts H9c2 cell line.
AB - Cocoa contains phenolic compounds with known antioxidant and antiradical
properties beneficial in different pathologies, including cardiovascular
diseases. Herein, we have evaluated the protective effects of clovamide, a minor
cocoa component, against oxidative stress induced in the rat cardiomyoblast cell
line, also comparing it to its bio-isosteric form, rosmarinic acid, and to the
main monomeric flavan-3-ol from low-molecular-weight polyphenol in cocoa, i.e.
epicatechin. At nano-micro-molar concentrations, the three compounds inhibited
the production of reactive oxygen species and apoptosis, evaluated under
different aspects, namely, annexin V positivity, DNA fragmentation, caspase
release and activation. These molecules can, thus, be considered for their
bioactive beneficial activity in the context of cardiovascular pathologies and,
particularly, in the protection towards oxidative stress that follows ischemic
injury. Clovamide may, thus, be the primary compound for the development of
innovative nutraceutical strategies towards cardiovascular diseases.
PMID- 25133995
TI - The real-time method of assessing the contribution of individual sources on
visibility degradation in Taichung.
AB - Visibility degradation caused by air pollution has become a serious environmental
problem in megacities in Northeast Asia. In general, aerosol chemical
compositions are measured by a conventional method of time integrated filter
sampling for off-line analysis, which cannot represent temporal and spatial
variations in the real atmosphere. The in situ air composition measuring
equipment, OCEC carbon aerosol analyzer and a long-path visibility
transmissometer-3 were used to collect hourly measurements of the soluble ions,
organic/elemental carbon, and ambient visibility, respectively. During the
observation, two types of weather conditions were identified: transport and
stagnant. Because PM2.5 was identified as the predominant species of light
extinction, the sources of PM2.5 were determined and investigated using a
positive matrix factorization (PMF) analysis. The PMF outputs characterized the
six main emission sources (marine/crustal aerosols, secondary nitrate, secondary
sulfate, direct vehicle exhaust, coal/incinerator combustion, and local sewage
emission) and reconstructed the PM2.5 mass concentrations of each pollutant
source in two weather conditions. In addition, the light extinction (bext) was
reconstructed using a multivariate linear regression analysis with hourly
reconstructed PM2.5 mass concentrations to determine the contributions of each
source to bext. The primary results showed that the extinction coefficient was
proportional to the PM2.5 with high value in stagnant weather conditions. The
secondary sulfate was the most abundant source of bext contribution during the
sampling period. In addition, the bext contributions of direct vehicle exhaust
and coal/incinerator combustion significantly increased in the stagnant weather
condition. According to the results of hourly measurements, this work further
emphasized that the sources of direct vehicle exhaust and coal/incinerator
combustion in PM2.5 were the important sources of visibility degradation in the
stagnant weather conditions, which suggests that the pollutants derived from
direct vehicle exhaust and coal/incinerator combustion should be controlled first
to improve visibility in Taichung.
PMID- 25133996
TI - Knee joint loading in knee osteoarthritis: influence of abdominal and thigh fat.
AB - PURPOSE: Using three separate models that included total body mass, total lean
and total fat mass, and abdominal and thigh fat as independent measures, we
determined their association with knee joint loads in older overweight and obese
adults with knee osteoarthritis (OA). METHODS: Fat depots were quantified using
computed tomography, and total lean and fat mass were determined with dual energy
x-ray absorptiometry in 176 adults (age, 66.3 yr; body mass index, 33.5 kg.m)
with radiographic knee OA. Knee moments and joint bone-on-bone forces were
calculated using gait analysis and musculoskeletal modeling. RESULTS: Higher
total body mass was significantly associated (P <= 0.0001) with greater knee
compressive and shear forces, compressive and shear impulses (P < 0.0001),
patellofemoral forces (P < 0.006), and knee extensor moments (P = 0.003).
Regression analysis with total lean and total fat mass as independent variables
revealed significant positive associations of total fat mass with knee
compressive (P = 0.0001), shear (P < 0.001), and patellofemoral forces (P = 0.01)
and knee extension moment (P = 0.008). Gastrocnemius and quadriceps forces were
positively associated with total fat mass. Total lean mass was associated with
knee compressive force (P = 0.002). A regression model that included total thigh
and total abdominal fat found that both were significantly associated with knee
compressive and shear forces (P <= 0.04). Thigh fat was associated with knee
abduction (P = 0.03) and knee extension moment (P = 0.02). CONCLUSIONS: Thigh
fat, consisting predominately of subcutaneous fat, had similar significant
associations with knee joint forces as abdominal fat despite its much smaller
volume and could be an important therapeutic target for people with knee OA.
PMID- 25133998
TI - Right ventricular fatigue developing during endurance exercise: an exercise
cardiac magnetic resonance study.
AB - INTRODUCTION: Prolonged intense exercise has often been associated with the
impairment of right ventricular (RV) function after activity, whereas this is
rare for the left ventricle (LV). The effect of prolonged exercise on the heart
has not been adequately measured during exercise itself. METHODS: We performed
real-time cardiac magnetic resonance imaging at rest and during incremental
exercise in 14 male endurance athletes (mean +/- SD; age = 36 +/- 6 yr, BMI =
23.1 +/- 1.94 kg.m) 1-3 wk before (baseline) and immediately after a 150-km
cycling event (end-of-race) to measure LV and RV end-diastolic and end-systolic
volumes (EDV and ESV), ejection fraction (EF), and ventricular-arterial coupling
(stroke volume [SV]/ESV). RESULTS: End-of-race RV EDV was unchanged from baseline
at rest but was significantly increased during near-maximal exercise (235 +/- 18
vs 217 +/- 24 mL, P < 0.0001). Resting RV ESV was higher end-of-race (100 +/- 16
vs 93 +/- 15 mL, P = 0.009), which became more appreciable during near-maximal
exercise (75 +/- 15 vs 60 +/- 14 mL, P < 0.0001). RV EF, although unchanged at
rest, was significantly decreased during near-maximal exercise (68% +/- 5% vs 73%
+/- 4%, P = 0.001). LV volume measures were similar at baseline and end-of-race.
Therefore, the effect of endurance activity on the RV and LV was significantly
different (P < 0.0001). Cardiac output increased to similar values at near
maximal exertion before and at the end of the race. However, whereas LV SV/ESV
was unchanged, RV SV/ESV was attenuated end-of-race (P = 0.02 for interaction
with race setting). CONCLUSIONS: Intense endurance exercise does not affect LV
volume or function but results in RV dilatation and reduced RV EF, which becomes
even more significant during exercise. Alterations in RV ventricular-arterial
coupling suggest that this may be an expression of exercise-induced RV
contractile impairment rather than changes in autonomic or loading conditions.
PMID- 25133997
TI - Resistance exercise, disability, and pain catastrophizing in obese adults with
back pain.
AB - PURPOSE: The purpose of this study was to compare the effects of two different
resistance exercise protocols on self-reported disability, fear avoidance
beliefs, pain catastrophizing, and back pain symptoms in obese, older adults with
low back pain (LBP). METHODS: Obese adults (n = 49, 60-85 yr) with chronic LBP
were randomized into a total body resistance exercise intervention (TOTRX),
lumbar extensor exercise intervention (LEXT), or a control group (CON). Main
outcomes included perceived disability (Oswestry Disability Index, Roland Morris
Disability Questionnaire). Psychosocial measures included the Fear Avoidance
Beliefs survey, Tampa Scale of Kinesiophobia, and Pain Catastrophizing Scale. LBP
severity was measured during three functional tasks: walking, stair climbing, and
chair rise using an 11-point numerical pain rating scale. RESULTS: The TOTRX
group had greater reductions in self-reported disability scores due to back pain
(Oswestry Disability Index, Roland Morris Disability Questionnaire) compared with
those in the LEXT (P < 0.05). The Pain Catastrophizing Scale scores decreased in
the TOTRX group compared with that in the CON group by month 4 (64.3% vs 4.8%, P
< 0.05). Pain severity during chair rise activity and walking was decreased in
both the LEXT and TOTRX groups relative to the CON group. CONCLUSIONS: Greater
reductions in perceived disability due to LBP can be achieved with TOTRX compared
with those achieved with LEXT. Pain catastrophizing and pain severity decreased
most with TOTRX. The positive change in psychological outlook may assist obese,
older adults with chronic back pain in reconsidering the harmfulness of the pain
and facilitate regular participation in other exercise programs.
PMID- 25133999
TI - Musculoskeletal risk factors as predictors of injury in community-dwelling women.
AB - BACKGROUND: Participating in health-related physical activity (PA) may increase
risk for musculoskeletal injury (MSI). PURPOSE: This study aimed to estimate the
prevalence of structural/biomechanical risk factors in community-dwelling women
and associated risk for incidence of MSI in women who are physically active.
METHODS: The Women's Injury study is a surveillance of PA behaviors and MSI in
women age 20-83 yr. An orthopedic examination was performed before entry into the
study to assess presence of structural/biomechanical risk factors. A total of 886
women completed data collection by reporting weekly PA behavior and MSI for up to
3 yr (2007-2009), with the average participant enrolled for 98 wk. To estimate
MSI risk associated with each risk factor separately, time to first MSI was
modeled using proportional hazard regression with time-dependent PA covariates,
controlling for age, body mass index, and previous injury. RESULTS: Over the
course of the study, 236 of the women (26.6%) reported at least one MSI that was
PA related. We found a significant association between the number of high
flexibility risk factors and PA-related injury at all levels of PA exposure (HR =
1.15 and confidence interval (CI) = 1.04-1.27 for moderate-to-vigorous PA; HR =
1.16 and CI = 1.05-1.28 for moderate PA; HR = 1.15 and CI = 1.04-1.27 for
vigorous PA). CONCLUSIONS: When participating at any level of PA for health
benefits, women with hypermobility in multiple muscle groups or joints should be
watchful for musculoskeletal symptoms and should be counseled not to ignore
symptoms when they first occur.
PMID- 25134000
TI - Functional overreaching: the key to peak performance during the taper?
AB - PURPOSE: The purpose of this study is to examine whether performance
supercompensation during taper is maximized in endurance athletes after
experiencing overreaching during an overload training (OT) period. METHODS:
Thirty-three trained male triathletes were assigned to either OT (n = 23) or
normal training groups (n = 10, CTL) during 8 wk. Cycling performance and maximal
oxygen uptake (VO2max) were measured after 1 wk of moderate training, a 3-wk
period of OT, and then each week during 4-wk taper. RESULTS: Eleven of the 23
subjects from the OT group were diagnosed as functionally overreached (F-OR)
after the overload period (decreased performance with concomitant high perceived
fatigue), whereas the 12 other subjects were only acutely fatigued (AF) (no
decrease in performance). According to qualitative statistical analysis, the AF
group demonstrated a small to large greater peak performance supercompensation
than the F-OR group (2.6% +/- 1.1%) and the CTL group (2.6% +/- 1.6%). VO2max
increased significantly from baseline at peak performance only in the CTL and AF
groups. Of the peak performances, 60%, 83%, and 73% occurred within the two first
weeks of taper in CTL, AF, and OR, respectively. Ten cases of infection were
reported during the study with higher prevalence in F-OR (70%) than that in AF
(20%) and CTL (10%). CONCLUSION: This study showed that 1) greater gains in
performance and VO2max can be achieved when higher training load is prescribed
before the taper but not in the presence of F-OR; 2) peak performance is not
delayed during taper when heavy training loads are completed immediately prior;
and 3) F-OR provides higher risk for training maladaptation, including increased
infection risks.
PMID- 25134001
TI - Glucose-fructose enhances performance versus isocaloric, but not moderate,
glucose.
AB - PURPOSE: The effects of glucose-and-fructose (GF) coingestion on cycling time
trial (TT) performance and physiological responses to exercise were examined
under postprandial conditions. METHODS: Eight trained male cyclists (age, 25 +/-
6 yr; height, 180 +/- 4 cm; weight, 77 +/- 9 kg; VO2max, 62 +/- 6 mL.kg.min)
completed the study. Subjects ingested either an artificially sweetened placebo
(PL), a moderate-glucose beverage (MG, 1.03 g.min), a high-glucose beverage (HG,
1.55 g.min), or a GF beverage (1.55 g.min, 2:1 ratio) during approximately 3 h of
exercise, including 2 h of constant-load cycling (55% Wmax, 195 +/- 17 W),
immediately followed by a computer-simulated 30-km TT. Physiological responses
(VE, VO2, RER, HR, blood glucose level, blood lactate level, and RPE) and
incidences of gastrointestinal distress were assessed during early (15-20 min),
middle (55-60 min), and late exercise (115-120 min) and during the TT. Magnitude
based qualitative inferences were used to evaluate differences between
treatments. RESULTS: In comparison with that in PL (52.9 +/- 3.7 min), TT
performances were faster with GF (50.4 +/- 2.2 min, "very likely" benefit), MG
(51.1 +/- 2.4 min, "likely" benefit), and HG (52.0 +/- 3.7 min, "possible"
benefit). GF resulted in a "likely" improvement versus HG (3.0%) and an "unclear"
effect relative to MG (1.2%). MG was "possibly" beneficial versus HG (1.8%). Few
incidences of GI distress were reported in any trials. CONCLUSIONS: GF ingestion
seems to enhance performance, relative to PL and HG. However, it is unclear
whether GF improves performance versus moderate doses of glucose.
PMID- 25134002
TI - Caffeine and performance over consecutive days of simulated competition.
AB - PURPOSE: Performance improvements after caffeine (CAF) ingestion are well
documented when using a 1-d protocol. In numerous competitions such as the Tour
de France, Tour de Ski, world championships, and National College Athletic
Association championships, athletes compete for several days in a row. To date,
no studies have investigated the effects of CAF when competing for consecutive
days in a row. This study aimed to investigate the effects of placebo (PLA) and
two different CAF doses (3 and 4.5 mg.kg body mass) on performance in a 10-min
all-out, cross-country, double poling ergometer test (C-PT) 2 d in a row. METHOD:
Eight highly trained male cross-country skiers (VO2max-run, 78.5 +/- 1.6
mL.kg.min) participated in the study, which was a randomized, double-blind, PLA
controlled, crossover design. Performance was assessed as distance covered during
a 10-min all-out C-PT. Oral ingestion of CAF or PLA was consumed 75 min before
the all-out C-PT. RESULTS: Poling distance was improved after CAF ingestions
compared with that after PLA on both days. The improvements on day 1 were 4.0%
(90% confidence limits, +/-3.3) and 4.0% +/- 2.9% for both CAF doses,
respectively (P < 0.05), whereas improvements on day 2 were 5.0% +/- 3.6% and
5.1% +/- 2.8% for CAF3 and CAF4.5, respectively, compared with those for PLA.
Improved performance was associated with increased HR, adrenaline concentration,
blood lactate concentration, and VO2 consumption after CAF ingestion.
Furthermore, performance was elevated despite higher creatine kinase
concentration and muscular pain at arrival on day 2 for both CAF doses.
CONCLUSIONS: Both CAF doses improved performance in the 10-min all-out C-PT
compared with PLA over two consecutive days. Therefore, CAF seems useful for
athletes competing over consecutive days despite higher muscle damage occurring
after enhanced performance on the first day.
PMID- 25134003
TI - Validation of accelerometer cut points in toddlers with and without cerebral
palsy.
AB - AIM: The purpose of this study was to validate uni- and triaxial ActiGraph cut
points for sedentary time in toddlers with cerebral palsy (CP) and typically
developing children (TDC). METHODS: Children (n = 103, 61 boys, mean age = 2 yr,
SD = 6 months, range = 1 yr 6 months-3 yr) were divided into calibration (n = 65)
and validation (n = 38) samples with separate analyses for TDC (n = 28) and
ambulant (Gross Motor Function Classification System I-III, n = 51) and
nonambulant (Gross Motor Function Classification System IV-V, n = 25) children
with CP. An ActiGraph was worn during a videotaped assessment. Behavior was coded
as sedentary or nonsedentary. Receiver operating characteristic-area under the
curve analysis determined the classification accuracy of accelerometer data.
Predictive validity was determined using the Bland-Altman analysis. RESULTS:
Classification accuracy for uniaxial data was fair for the ambulatory CP and TDC
group but poor for the nonambulatory CP group. Triaxial data showed good
classification accuracy for all groups. The uniaxial ambulatory CP and TDC cut
points significantly overestimated sedentary time (bias = -10.5%, 95% limits of
agreement [LoA] = -30.2% to 9.1%; bias = -17.3%, 95% LoA = -44.3% to 8.3%). The
triaxial ambulatory and nonambulatory CP and TDC cut points provided accurate
group-level measures of sedentary time (bias = -1.5%, 95% LoA = -20% to 16.8%;
bias = 2.1%, 95% LoA = -17.3% to 21.5%; bias = -5.1%, 95% LoA = -27.5% to 16.1%).
CONCLUSION: Triaxial accelerometers provide useful group-level measures of
sedentary time in children with CP across the spectrum of functional abilities
and TDC. Uniaxial cut points are not recommended.
PMID- 25134004
TI - Predicting physical activity energy expenditure in manual wheelchair users.
AB - PURPOSE: This study aimed to assess the influence of anatomical placement of an
accelerometer on physical activity energy expenditure prediction in manual
wheelchair users. METHODS: Ten accelerometer units (ActiGraph GT3X+) were
attached to a multiaxis shaker table and subjected to a sinusoidal oscillation
procedure to assess mechanical validity and reliability. Fifteen manual
wheelchair users (mean +/- SD: age, 36 +/- 11 yr; body mass, 70 +/- 12 kg) then
completed five activities, including desk work and wheelchair propulsion (2, 4,
6, and 8 km.h). Expired gases were collected throughout. GT3X+ accelerometers
were worn on the right wrist, upper arm, and waist. The relations between
physical activity counts and metabolic rate were subsequently assessed, and bias
+/- 95% limits of agreement was calculated. RESULTS: During mechanical testing,
coefficients of variation ranged from 0.2% to 4.7% (intraunit) and 0.9% to 5.2%
(interunit) in all axes. During human exercise testing, physical activity counts
at each anatomical location was significantly (P < 0.01) correlated with
metabolic rate (wrist, r = 0.93; upper arm, r = 0.87; waist, r = 0.73). The SEE
for each correlation were 3.34, 4.38, and 6.07 kJ.min for the wrist, upper arm,
and waist, respectively. The absolute bias +/- 95% limits of agreement values
were 0.0 +/- 6.5 kJ.min, 0.0 +/- 8.5 kJ.min, and 0.0 +/- 11.8 kJ.min for the
wrist, upper arm, and waist, respectively. CONCLUSIONS: The ActiGraph GT3X+ is a
reliable tool for determining mechanical movements within the physiological range
of human movement. Of the three anatomical locations considered, a wrist-mounted
accelerometer explains more of the variance and results in the lowest random
error when predicting physical activity energy expenditure in manual wheelchair
users.
PMID- 25134007
TI - Efficient electrocatalytic oxygen evolution on amorphous nickel-cobalt binary
oxide nanoporous layers.
AB - Nanoporous Ni-Co binary oxide layers were electrochemically fabricated by
deposition followed by anodization, which produced an amorphous layered structure
that could act as an efficient electrocatalyst for water oxidation. The highly
porous morphologies produced higher electrochemically active surface areas, while
the amorphous structure supplied abundant defect sites for oxygen evolution.
These Ni-rich (10-40 atom % Co) binary oxides have an increased active surface
area (roughness factor up to 17), reduced charge transfer resistance, lowered
overpotential (~325 mV) that produced a 10 mA cm(-2) current density, and a
decreased Tafel slope (~39 mV decade(-1)). The present technique has a wide range
of applications for the preparation of other binary or multiple-metals or metal
oxides nanoporous films. Fabrication of nanoporous materials using this method
could provide products useful for renewable energy production and storage
applications.
PMID- 25134005
TI - Predicting human movement with multiple accelerometers using movelets.
AB - PURPOSE: The study aims were 1) to develop transparent algorithms that use short
segments of training data for predicting activity types and 2) to compare the
prediction performance of the proposed algorithms using single accelerometers and
multiple accelerometers. METHODS: Sixteen participants (age, 80.6 yr (4.8 yr);
body mass index, 26.1 kg.m (2.5 kg.m)) performed 15 lifestyle activities in the
laboratory, each wearing three accelerometers at the right hip and left and right
wrists. Triaxial accelerometry data were collected at 80 Hz using ActiGraph
GT3X+. Prediction algorithms were developed, which, instead of extracting
features, build activity-specific dictionaries composed of short signal segments
called movelets. Three alternative approaches were proposed to integrate the
information from the multiple accelerometers. RESULTS: With at most several
seconds of training data per activity, the prediction accuracy at the second
level temporal resolution was very high for lying, standing, normal/fast walking,
and standing up from a chair (the median prediction accuracy ranged from 88.2% to
99.9% on the basis of the single-accelerometer movelet approach). For these
activities, wrist-worn accelerometers performed almost as well as hip-worn
accelerometers (the median difference in accuracy between wrist and hip ranged
from -2.7% to 5.8%). Modest improvements in prediction accuracy were achieved by
integrating information from multiple accelerometers. DISCUSSION AND CONCLUSIONS:
It is possible to achieve high prediction accuracy at the second-level temporal
resolution with very limited training data. To increase prediction accuracy from
the simultaneous use of multiple accelerometers, a careful selection of
integrative approaches is required.
PMID- 25134009
TI - Tracking of azobenzene isomerization by X-ray emission spectroscopy.
AB - Cis-trans isomerizations are among the fundamental processes in photochemistry.
In azobenzene or its derivatives this dynamics is, due to its reversibility, one
of the reactions widely used in photostimulation of molecular motors or in
molecular electronics. Though intensively investigated in the optical regime, no
detailed study exists in the X-ray regime so far. Because the X-ray emission
spectroscopy echoes the electronic structure sensitive to the geometry, this
theoretical report based on the density functional theory and its time-dependent
version presents different nitrogen K-edge X-ray emission spectra for cis and
trans isomers with close interrelation to their electron configuration.
Considering the spectrum along the isomerization path, these structural
signatures can be utilized to probe the isomerization dynamics in the excited
molecule. The scheme can further be generalized to the element specific
photoreactions.
PMID- 25134010
TI - Design and synthesis of new stable fluorenyl-based radicals.
AB - Organic neutral radicals have long fascinated chemists with a fundamental
understanding of structure-reactivity relationships in organic reactions and with
applications as new functional materials. However, the elusive nature of these
radicals makes the synthesis, isolation, and characterization very challenging.
In this work, the synthesis of three long-lived, fluorenyl-based radicals are
reported. The geometry and electronic structures of these radicals were
systematically investigated with a combination of various experimental methods,
besides density functional theory (DFT) calculations, which include X-ray
crystallographic analysis, electron spin resonance (ESR), electron nuclear double
resonance (ENDOR), cyclic voltammetry, and UV-vis-NIR measurements. Their half
life periods (tau(1/2)) in air-saturated solution under ambient conditions were
also determined. Surprisingly, all three radicals showed remarkable stabilities:
tau(1/2) = 7, 3.5, and 43 days.
PMID- 25134008
TI - LC-MS/MS quantitation of esophagus disease blood serum glycoproteins by
enrichment with hydrazide chemistry and lectin affinity chromatography.
AB - Changes in glycosylation have been shown to have a profound correlation with
development/malignancy in many cancer types. Currently, two major enrichment
techniques have been widely applied in glycoproteomics, namely, lectin affinity
chromatography (LAC)-based and hydrazide chemistry (HC)-based enrichments. Here
we report the LC-MS/MS quantitative analyses of human blood serum glycoproteins
and glycopeptides associated with esophageal diseases by LAC- and HC-based
enrichment. The separate and complementary qualitative and quantitative data
analyses of protein glycosylation were performed using both enrichment
techniques. Chemometric and statistical evaluations, PCA plots, or ANOVA test,
respectively, were employed to determine and confirm candidate cancer-associated
glycoprotein/glycopeptide biomarkers. Out of 139, 59 common glycoproteins (42%
overlap) were observed in both enrichment techniques. This overlap is very
similar to previously published studies. The quantitation and evaluation of
significantly changed glycoproteins/glycopeptides are complementary between LAC
and HC enrichments. LC-ESI-MS/MS analyses indicated that 7 glycoproteins enriched
by LAC and 11 glycoproteins enriched by HC showed significantly different
abundances between disease-free and disease cohorts. Multiple reaction monitoring
quantitation resulted in 13 glycopeptides by LAC enrichment and 10 glycosylation
sites by HC enrichment to be statistically different among disease cohorts.
PMID- 25134011
TI - NHC copper(I) complexes bearing dipyridylamine ligands: synthesis, structural,
and photoluminescent studies.
AB - We describe the synthesis of new cationic tricoordinated copper complexes bearing
bidentate pyridine-type ligands and N-heterocyclic carbene as ancillary ligands.
These cationic copper complexes were fully characterized by NMR,
electrochemistry, X-ray analysis, and photophysical studies in different
environments. Density functional theory calculations were also undertaken to
rationalize the assignment of the electronic structure and the photophysical
properties. These tricoordinated cationic copper complexes possess a stabilizing
CH-pi interaction leading to high stability in both solid and liquid states. In
addition, these copper complexes, bearing dipyridylamine ligands having a central
nitrogen atom as potential anchoring point, exhibit very interesting luminescent
properties that render them potential candidates for organic light-emitting diode
applications.
PMID- 25134012
TI - The effect of the sulfur position on the melting points of lipidic 1-methyl-3
thiaalkylimidazolium ionic liquids.
AB - A series of novel lipid-inspired ionic liquids have been synthesized employing
the thiol-ene "click" reaction in a single-step process. The thermal properties
were determined by differential scanning calorimetry (DSC) and showed observable
trends between the C16, C18, and C20 analogues. The minimum melting points for
each equivalent chain length series occur at sequential odd sulfur positions, 3,
5, and 7 for the C16, C18, and C20 series, respectively. The magnitude of melting
point depression relative to the saturated homologue is observed to have a strong
dependence on the position of the sulfur in the side chain. Additionally, the
sulfur position corresponding to the lowest melting point for a homologous series
shifts further down the chain as the chain length is increased, indicating that
the maximum effect takes place near the center of the ion and not the center of
the thiaalkyl chain. This synthesis provides tunability and improved thermal
stability for 1-methyl-3-thiaalkylimidazolium bistriflimides and insight into
structure-property relationships of lipidic ionic liquids.
PMID- 25134013
TI - Influence of net energy content of the diets on productive performance and
carcass merit of gilts, boars and immunocastrated males slaughtered at 120kg BW.
AB - In total, 540 crossbred pigs with an initial body weight of 28.5kg were used to
investigate the effects of the net energy (NE) content (2.29, 2.33, 2.37, 2.41
and 2.45 Mcal/kg) of the diet on growth performance and carcass and meat quality
traits of gilts, boars and immunocastrated males (IMC). An increase in dietary NE
increased NE intake and decreased feed conversion ratio linearly. The IMC pigs
showed greater feed intake and average daily gain than gilts and boars. Backfat
depth increased and chilled and trimmed ham yield decreased, as the dietary NE
increased. Backfat depth was greater for gilts and IMC than for boars. Also,
gilts had greater carcass and loin yields than boars and IMC. Diets with the
greater NE content were more appropriate for the production of heavy pigs.
However, the economic interest of this practice needs further assessment.
PMID- 25134014
TI - Differentiation of meat from European wild boars and domestic pigs using
polymorphisms in the MC1R and NR6A1 genes.
AB - Wild boar meat cannot be easily distinguished from domestic pig meat, especially
in processed products, thus it can be fraudulently substituted with cheaper
domestic pork. In this study we genotyped polymorphisms in two genes (MC1R,
affecting coat color and NR6A1, associated with number of vertebrae) in 293
domestic pigs of five commercial breeds, 111 wild boars sampled in Italy, and 90
in Slovenia and other Western Balkan regions. Allele and genotype frequency data
were used to set up a DNA-based method to distinguish meat of wild boars and
domestic pigs. Genotyping results indicated that domesticated genes were
introgressed into wild boar populations. This complicated the determination of
the origin of the meat and would cause a high error rate if markers of only one
gene were used. The combined use of polymorphisms in the two analyzed genes
substantially reduced false negative results.
PMID- 25134016
TI - Steam electrolysis by solid oxide electrolysis cells (SOECs) with proton
conducting oxides.
AB - Energy crisis and environmental problems caused by the conventional combustion of
fossil fuels boost the development of renewable and sustainable energies. H2 is
regarded as a clean fuel for many applications and it also serves as an energy
carrier for many renewable energy sources, such as solar and wind power. Among
all the technologies for H2 production, steam electrolysis by solid oxide
electrolysis cells (SOECs) has attracted much attention due to its high
efficiency and low environmental impact, provided that the needed electrical
power is generated from renewable sources. However, the deployment of SOECs based
on conventional oxygen-ion conductors is limited by several issues, such as high
operating temperature, hydrogen purification from water, and electrode stability.
To avoid these problems, proton-conducting oxides are proposed as electrolyte
materials for SOECs. This review paper provides a broad overview of the research
progresses made for proton-conducting SOECs, summarizing the past work and
finding the problems for the development of proton-conducting SOECs, as well as
pointing out potential development directions.
PMID- 25134015
TI - Effect of partial reduction of pork meat on the physicochemical and sensory
quality of dry ripened sausages: development of a healthy venison salchichon.
AB - The minimum percentage of pork meat to be added to traditional venison salchichon
has been determined in order to ensure a nutritionally healthier product without
impairing physicochemical or sensory properties. Six types of salchichon were
made using lean venison and a varying amount of pork meat (40%, 30%, 25%, 20%,
15% and 10%). All types displayed appropriate physicochemical properties (pH, aw,
moisture loss) and color (L*, a*, b*) during ripening, as well as adequate levels
of lipolysis (acidity index) and lipid oxidation (TBARS). Moreover, reduction of
the amount of pork meat in salchichon prompted an increase in the relative
percentage of polyunsaturated fatty acids. It was concluded that in making
venison salchichon, the addition of a 25% pork meat is sufficient to ensure a
satisfactory ripening process and physicochemical characteristics, optimal
organoleptic properties and a higher percentage of polyunsaturated fatty acids
than that found in traditional venison salchichon.
PMID- 25134017
TI - Engineered M13 bacteriophage nanocarriers for intracellular delivery of exogenous
proteins to human prostate cancer cells.
AB - The size, well-defined structure, and relatively high folding energies of most
proteins allow them to recognize disease-relevant receptors that present a
challenge to small molecule reagents. While multiple challenges must be overcome
in order to fully exploit the use of protein reagents in basic research and
medicine, perhaps the greatest challenge is their intracellular delivery to a
particular diseased cell. Here, we describe the genetic and enzymatic
manipulation of prostate cancer cell-penetrating M13 bacteriophage to generate
nanocarriers for the intracellular delivery of functional exogenous proteins to a
human prostate cancer cell line.
PMID- 25134018
TI - Self-assembly of a Ag nanoparticle-modified and graphene-wrapped TiO2 nanobelt
ternary heterostructure: surface charge tuning toward efficient photocatalysis.
AB - In recent years, tremendous research efforts have been made towards developing
graphene (GR)-based nanocomposites for photocatalytic applications. In this work,
surface-coarsened TiO2 nanobelts (SC-TNBs) closely enwrapped with monodispersed
Ag nanoparticles (NPs) and GR nanosheets (i.e. Ag/GR/SC-TNBs) were fabricated
using a facile self-assembly strategy followed by photoreduction. It was found
that the as-prepared Ag/GR/SC-TNBs ternary heterostructure exhibited
significantly improved photocatalytic performances under irradiation with UV
light in comparison with blank SC-TNBs and its binary counterparts owing to the
formation of double heterojunctions among the components. The intimate
integration of Ag NPs and GR with SC-TNBs achieved by the self-assembly buildup
exerts a profound effect on the transfer of photogenerated electrons over the SC
TNBs substrate in which Ag NPs serve as an efficient "electron reservoir" and GR
as an electron transporter and collector, thus concurrently prolonging the
lifetime of the photogenerated electron-hole pairs and resulting in the
remarkably enhanced photoactivity over the Ag/GR/SC-TNBs ternary nanocomposite.
In addition, the underlying photocatalytic mechanism was elucidated and the
primary active species were determined.
PMID- 25134019
TI - Liverpool Active City 2005-2010: Increasing Population Physical Activity Levels
Through Intersectoral Action.
AB - BACKGROUND: The process of working together across sectors to improve health and
to influence its determinants is often referred to as intersectoral action for
health. The Liverpool Active City strategy and action plan were launched in 2005,
bringing together partners from diverse sectors such as education, transport, and
civil society to boost levels of physical activity among the city's residents.
METHODS: The research material was based on semistructured interviews with key
stakeholders and on review and analysis of gray literature and media reports. A
case-study method was used to analyze the experience. RESULTS: The results show
that Liverpool Active City succeeded in boosting levels of physical activity
among the city's residents and demonstrate how intersectoral action benefited the
goals of the program and promoted common aims. CONCLUSIONS: Important lessons can
be drawn from the experience of Liverpool Active City for public health
professionals and policy makers. Success factors include the involvement of a
broad range of agencies from a variety of sectors, which reinforced the sense of
partnership in the physical activity agenda and supported the implementation of
activities. The experience also demonstrated how intersectoral action brought
benefits to the physical activity goals of Liverpool Active City.
PMID- 25134020
TI - A novel fluorescent conjugate applicable to visualize the translocation of
glucose-fipronil.
AB - The ability to visualize the movement of glycosyl insecticides contributes to
learning their translocation and distribution in plants. In our present work, a
novel fluorescent glucose-fipronil conjugate N-[3-cyano-1-[2,6-dichloro-4
(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazol-5-yl]-1-(2-[N
(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-beta-D-glucopyranosyl)-1H-1,2,3
triazole-4-methanamine (2-NBDGTF), was obtained via click chemistry. Disk uptake
experiments showed that an active carrier-mediated system was involved in the 2
NBDGTF uptake process. Meanwhile, 2-NBDGTF exhibited comparable phloem mobility
with GTF in castor bean seedlings. Visualization of 2-NBDGTF uptake and transport
experiment showed that this fluorescent glucose-fipronil conjugate could be
loaded into sieve tubes after transiting through epidermal cells and mesophyll
cells and then translocate from cotyledon to hypocotyl via phloem in castor bean
seedlings. The results above determined that it is a promising fluorescence
tagging approach for revealing the activities of glycosyl insecticides and 2
NBDGTF is a reasonable and feasible fluorescent surrogate of GTF for tracing the
distribution of glucose-fipronil conjugates.
PMID- 25134021
TI - An experience sampling study of PTSD and alcohol-related problems.
AB - Posttraumatic stress disorder (PTSD) represents a debilitating psychiatric
condition that is affecting the lives of many returning veterans. PTSD and
alcohol use and dependence are highly comorbid. The purpose of this study was to
understand the functional mechanisms between PTSD and alcohol use and problems.
Specifically, the role of negative urgency and emotional intelligence were
investigated as vulnerability and resiliency factors, respectively. This study
utilized experience sampling to test associations between PTSD symptoms and
alcohol use and related problems in a sample of 90 OIF/OEF veterans. Participants
completed 8 brief questionnaires daily for 2 weeks on palmtop computers.
Elevations in PTSD symptoms during the day were associated with subsequent
increases in alcohol use and associated problems that night. PTSD symptoms were
associated with greater problems above and beyond the effect of drinking level at
both the within- and between- person level. Emotional intelligence was associated
with lower negative urgency, fewer PTSD symptoms, and less alcohol use and
associated problems. The effects of emotional intelligence were primarily
indirect via negative urgency and the effects of negative urgency on alcohol use
and problems were indirect via its positive association with PTSD symptoms.
Hypothesized cross-level effects of emotional intelligence and negative urgency
were not supported. The findings suggest a functional association between PTSD
symptoms and alcohol consumption. The association between PTSD symptoms and
alcohol consumption is consistent with a self-medication model. However, the
significant associations between PTSD symptoms and alcohol problems, after
controlling for use level, suggest a broader role of dysregulation.
PMID- 25134022
TI - Two alternative approaches to conventional person-mean imputation scoring of the
Self-Rating of the Effects of Alcohol Scale (SRE).
AB - A low level of response to alcohol is considered a significant risk factor for
alcohol use disorder. Survey measures of this construct assess the number of
drinks required to experience various alcohol effects, so data will be missing
for effects participants have not experienced. Furthermore, missingness will
likely be more common for items with higher means, as more severe effects are
likely experienced both less commonly and at higher consumption levels. We
explored whether these atypical characteristics of response-to-alcohol survey
data cause problems when using conventional person-mean imputation scoring. This
scoring approach involves averaging across nonmissing items for each participant,
implicitly assuming that missing items have similar distributional properties
(e.g., means) as nonmissing items. Analyses used data from the most commonly
utilized response-to-alcohol survey measure: The Self-Rating of the Effects of
Alcohol Scale (SRE). Results (a) revealed a strong relationship between higher
item means and greater item missingness, (b) established that this relation
causes person-mean imputation to produce more downwardly biased response-to
alcohol summary scores for participants with more missing data, (c) established
that this induced a spurious relationship between higher response-to-alcohol
summary scores and higher alcohol-effect endorsement (i.e., the number of SRE
alcohol effects experienced), and (d) found that these biases can be reduced with
2 alternative scoring approaches. We discuss these and other potential problems
with person-mean imputation, and common and unique advantages of the 2
alternative approaches. We consider generalizability, including how the problems
shown here may vary in practical significance across different populations and
measures. (PsycINFO Database Record
PMID- 25134023
TI - Alcohol-related cues potentiate alcohol impairment of behavioral control in
drinkers.
AB - The acute impairing effects of alcohol on inhibitory control are well
established, and these disinhibiting effects are thought to play a role in its
abuse potential. Alcohol impairment of inhibitory control is typically assessed
in the context of arbitrary cues, yet drinking environments are comprised of an
array of alcohol-related cues that are thought to influence drinking behavior.
Recent evidence suggests that alcohol-related stimuli reduce behavioral control
in sober drinkers, suggesting that alcohol impairment of inhibitory control might
be potentiated in the context of alcohol cues. The current study tested this
hypothesis by examining performance on the attentional-bias behavioral activation
(ABBA) task that measures the degree to which alcohol-related stimuli can reduce
inhibition of inappropriate responses in a between-subjects design. Social
drinkers (N = 40) performed the task in a sober condition, and then again
following placebo (0.0 g/kg) and a moderate dose of alcohol (0.65 g/kg) in
counterbalanced order. Inhibitory failures were greater following alcohol images
compared to neutral images in sober drinkers, replicating previous findings with
the ABBA task. Moreover, alcohol-related cues exacerbated alcohol impairment of
inhibitory control as evidenced by more pronounced alcohol-induced disinhibition
following alcohol cues compared to neutral cues. Finally, regression analyses
showed that greater alcohol-induced disinhibition following alcohol cues
predicted greater self-reported alcohol consumption. These findings have
important implications regarding factors contributing to binge or "loss of
control" drinking. That is, the additive effect of disrupted control mechanisms
via both alcohol cues and the pharmacological effects of the drug could
compromise an individual's control over ongoing alcohol consumption. (PsycINFO
Database Record
PMID- 25134024
TI - Using ecological measures of smoking trigger exposure to predict smoking
cessation milestones.
AB - This study used ecological momentary assessment data from adult daily smokers
attempting to quit smoking to assess relations between exposure to contextual
risk factors and cessation failure, latency to a first smoking lapse, or
progression from lapse to relapse (smoking 7 days in a row). Participants were
adult, daily smokers enrolled in a randomized controlled clinical trial of
bupropion SR and individual counseling who were followed to 1 year postquit.
Participants reported exposure to high-risk contexts and behaviors, including
being where cigarettes were available or smoking was permitted, being around
others smoking in prospective, real-time assessment for 2 weeks pre- and 4 weeks
postquit. Results showed that greater exposure to contextual risk factors during
the prequit did not predict cessation failure. However, Cox regression survival
analyses revealed that spending a greater proportion of time where cigarettes
were easily available following at least 1 day of abstinence predicted shorter
latency to a first lapse, even after controlling for baseline risk factors such
as gender, nicotine dependence, depressive symptoms, and living with a smoker.
Greater cigarette availability following a lapse was not associated with
progression from lapse to relapse with or without baseline risk factors in the
model. This suggests that postquit environmental risk factors, such as cigarette
availability, increase lapse risk, and stable risk factors, such as living with
smokers and higher baseline carbon monoxide level or depressive symptoms, remain
potent predictors of progression to relapse. Real-time contextual risk
assessments postquit predict lapse above and beyond stable, baseline risk
factors. (PsycINFO Database Record
PMID- 25134026
TI - Gambling disorder: estimated prevalence rates and risk factors in Macao.
AB - An excessive, problematic gambling pattern has been regarded as a mental disorder
in the Diagnostic and Statistical Manual for Mental Disorders (DSM) for more than
3 decades (American Psychiatric Association [APA], 1980). In this study, its
latest prevalence in Macao (one of very few cities with legalized gambling in
China and the Far East) was estimated with 2 major changes in the diagnostic
criteria, suggested by the 5th edition of DSM (APA, 2013): (a) removing the
"Illegal Act" criterion, and (b) lowering the threshold for diagnosis. A random,
representative sample of 1,018 Macao residents was surveyed with a phone poll
design in January 2013. After the 2 changes were adopted, the present study
showed that the estimated prevalence rate of gambling disorder was 2.1% of the
Macao adult population. Moreover, the present findings also provided empirical
support to the application of these 2 recommended changes when assessing symptoms
of gambling disorder among Chinese community adults. Personal risk factors of
gambling disorder, namely being male, having low education, a preference for
casino gambling, as well as high materialism, were identified.
PMID- 25134027
TI - Anxiety sensitivity as a moderator of the relationship between trait anxiety and
illicit substance use.
AB - Anxiety and substance use problems are common and often comorbid, and past
research has shown that young adults in particular are especially at risk for
developing these disorders. To further delineate the relationship between anxiety
and substance use, the current study evaluated anxiety sensitivity (AS)-a
cognitive vulnerability factor-as a moderator of the association between trait
anxiety and illicit substance use in a large sample of young adults (N = 845; M =
18.7 years, SD = 1.0). It was hypothesized that AS would moderate the association
between trait anxiety and illicit substance use, such that trait anxiety would
significantly predict illicit substance use among those with high, but not low,
AS. Consistent with prediction, a significant trait Anxiety * AS interaction was
found, chi2(5) = 29.38, p < .001. Specifically, analyses of simple slopes
revealed that for the high-AS group, as trait anxiety increased, so did frequency
of illicit substance use (odds ratio [OR] = 1.03, p = .005; 95% confidence
interval [CI] [1.01, 1.06]). The slope for the low AS was not significant (OR =
0.98, p = .100; 95% CI [0.95, 1.01]). Results also showed significant moderation
effects for the AS physical concerns and cognitive concerns facets but not AS
social concerns. These findings suggest that AS may be an important cognitive
vulnerability that may help to identify those at particular risk for substance
use, and that interventions should target AS reduction in anxiety-prone
individuals to reduce and prevent substance abuse.
PMID- 25134025
TI - Relational aggression, positive urgency and negative urgency: predicting alcohol
use and consequences among college students.
AB - Research on relational aggression (indirect and social means of inflicting harm)
has previously focused on adolescent populations. The current study extends this
research by exploring both the frequency of perpetrating and being the target of
relational aggression as it relates to alcohol use outcomes in a college
population. Further, this study examines whether positive urgency (e.g., acting
impulsively in response to positive emotions) and negative urgency (e.g., acting
impulsively in response to negative emotions) moderate the relationship between
relational aggression and alcohol outcomes. In this study, 245 college students
(65.7% female) completed an online survey. Results indicated greater frequency of
perpetrating relational aggression, higher levels of positive urgency, or higher
levels of negative urgency was associated with more negative consequences.
Further, negative urgency moderated the relationship between frequency of
perpetrating aggression and consequences such that aggression was more strongly
associated with consequences for those high in urgency. Counter to the adolescent
literature, the frequency of being the target of aggression was not associated
with more alcohol use. These findings suggest that perpetrators of relational
aggression may be at particular risk for negative alcohol-related consequences
when they act impulsively in response to negative, but not positive, emotions.
These students may benefit from interventions exploring alternative ways to cope
with negative emotions.
PMID- 25134028
TI - A longitudinal analysis of drinking and victimization in college women: is there
a reciprocal relationship?
AB - The purpose of the current study was to assess the relationship between drinking
and severe physical and sexual victimization in a sample of 989 college women
over 5 years. Participants completed a Web-based survey each fall semester,
beginning as first-time incoming freshman, and continuing each year for 5 years.
The survey was comprehensive in assessing drinking, victimization, and relevant
covariates. Women were followed whether they remained at university or not. Prior
year same type of severe victimization predicted current year victimization, both
severe physical and sexual. However, prior year drinking did not predict current
year severe victimization. Prior year severe sexual victimization predicted
current year drinking. Our findings of a longitudinal relationship between severe
sexual victimization and subsequent increases in drinking suggests that college
women may be drinking to cope with negative sequelae that they experience as a
result of the victimization. We did not find the same longitudinal relationship
between drinking and severe physical or sexual victimization, suggesting that a
reciprocal relationship does not exist between drinking and victimization among
college women. We did find that severe sexual victimization decreased across
college, suggesting that the year prior to and the first year of college may be a
critical period for intervening to reduce risk for severe victimization.
PMID- 25134031
TI - Differential association of drinking motives with alcohol use on weekdays and
weekends.
AB - Drinking motives (DM) reflect the reasons why individuals drink alcohol. Weekdays
are mainly dedicated to work, whereas weekends are generally associated with
spending time with friends during special events or leisure activities; using
alcohol on weekdays and weekends may also be related to different DM. This study
examined whether DM were differentially associated with drinking volume (DV) on
weekdays and weekends. A representative sample of 5,391 young Swiss men completed
a questionnaire assessing weekday and weekend DV, as well as their DM, namely,
enhancement, social, coping, and conformity motives. Associations of DM with
weekday and weekend DV were examined using structural equation models. Each DM
was tested individually in a separate model; all associations were positive and
generally stronger (except conformity) for weekend rather than for weekday DV.
Further specific patterns of association were found when DM were entered into a
single model simultaneously. Associations with weekday and with weekend DV were
positive for enhancement and coping motives. However, associations were stronger
with weekend rather than with weekday DV for enhancement, and stronger with
weekday than with weekend DV for coping motives. Associations of social motives
were not significant with weekend DV and negative with weekday DV. Conformity
motives were negatively associated with weekend DV and positively related to
weekday DV. These results suggest that interventions targeting enhancement
motives should be particularly effective at decreasing weekend drinking, whereas
interventions targeted at coping motives would be particularly effective at
reducing alcohol use on weekdays.
PMID- 25134030
TI - Internalizing and externalizing problem behavior and early adolescent substance
use: a test of a latent variable interaction and conditional indirect effects.
AB - Externalizing problem behavior is a robust predictor of early adolescent
substance use (SU); however, findings regarding internalizing problems have been
mixed, suggesting that there may be important moderators of the relationship
between internalizing problems and SU. The present study used a community sample
(mean age was 12.1 at the first assessment, 55% women, 83% White) to test a
longitudinal latent variable interaction structural equation model to examine
whether externalizing problems moderated the relationship between internalizing
problems and SU. Peer delinquency was tested as a mediator in the model and prior
levels of the mediator and outcome were controlled at each wave to establish
temporal precedence. Results suggested that (1) internalizing problems were
protective against associating with deviant peers, but only at high levels of
externalizing symptomatology, (2) higher levels of peer delinquency were
associated with increases in SU, and (3) peer delinquency mediated the effect of
the problem behavior interaction on SU. Our findings suggest that the impact of
internalizing problems on peer delinquency and SU needs to be considered in the
context of externalizing problems. Moreover, developmental models involving
internalizing symptoms should consider that internalizing symptoms are generally
protective against substance use in early adolescence.
PMID- 25134029
TI - Childhood stress exposure among preadolescents with and without family histories
of substance use disorders.
AB - Having a family history of substance use disorders (FH+) increases risk for
developing a substance use disorder. This risk may be at least partially mediated
by increased exposure to childhood stressors among FH+ individuals. However,
measures typically used to assess exposure to stressors are narrow in scope and
vary across studies. The nature of stressors that disproportionately affect FH+
children and how these stressors relate to later substance use in this population
are not well understood. The purpose of this study was to assess exposure to a
broad range of stressors among FH+ and FH- children to better characterize how
exposure to childhood stressors relates to increased risk for substance misuse
among FH+ individuals. A total of 386 children (305 FH+, 81 FH-; ages 10-12) were
assessed using the Stressful Life Events Schedule before the onset of regular
substance use. Both the number and severity of stressors were compared.
Preliminary follow-up analyses were done for 53 adolescents who subsequently
reported initiation of substance use. FH+ children reported more frequent and
severe stressors than did FH- children, specifically in the areas of housing,
family, school, crime, peers, and finances. Additionally, risk for substance use
initiation during early adolescence was influenced directly by having a family
history of substance use disorders and also indirectly through increased exposure
to stressors among FH+ individuals. In conclusion, FH+ children experience
greater stress across multiple domains, which contributes to their risk for
substance misuse and related problems during adolescence and young adulthood.
(PsycINFO Database Record
PMID- 25134032
TI - Self-perceived emerging adult status and substance use.
AB - Very little research exists on how self-perceived emerging adult status is
associated with substance use among low-income emerging adults. The Inventory of
Dimensions of Emerging Adulthood (IDEA) was administered to emerging adults (EAs)
ages 18-25 screened for substance use problems (n = l05) in a state-subsidized,
not-for-profit treatment agency. We examined whether the defining dimensions of
Arnett's (2000a) emerging adulthood theory were associated with substance use
frequency and substance-related problems, including: identity exploration, self
focus, possibilities, optimism, negativity/instability, and feeling in-between.
In multivariate models, feeling in-between was positively associated with
substance-related problems. An interaction term between minority status and
feeling in-between approached statistical significance (p = .057). Further, IDEA
scale score means were comparable to those found in college student samples.
Implications for theory revision are discussed.
PMID- 25134033
TI - Advantages and disadvantages of college drinking in students' own words: content
analysis of the decisional balance worksheet.
AB - The decisional balance worksheet (DBW), an open-ended measure of motivation to
change, may be used to record the perceived advantages and disadvantages of
substance use as well as alternative behaviors. Recent findings have indicated
that the open-ended DBW can be quantified to validly reflect college students'
level of motivation to reduce their drinking (Collins, Carey, & Otto, 2009). The
goal of the current study was to enhance our understanding of college students'
perceived advantages and disadvantages of drinking by qualitatively examining the
content of their decisional balance. Participants were undergraduate college
students at a 4-year university (N = 760) who participated in a randomized
controlled trial of online brief motivational interventions. Using the DBW,
participants recorded the advantages and disadvantages of their current drinking.
Conventional content analysis methods were used to extract common themes. Social,
enjoyment, and psychological reasons were the most commonly mentioned advantages
of drinking, whereas physical side effects, expense and interference with goals
were the most commonly mentioned disadvantages of drinking. These findings show
that college students primarily use alcohol for enjoyment, particularly in social
situations, as well as for coping with stress and social anxiety. On the other
hand, many college students report having physical side effects from drinking as
well as other kinds of concerns (e.g., expense, calories). Findings suggest that
using the open-ended DBW may result in a more client-centered and accurate
representation of what college students perceive as advantages and disadvantages
to drinking than established, Likert-scale measures of decisional balance.
PMID- 25134034
TI - Profiles of confidence and commitment to change as predictors of moderated
drinking: a person-centered approach.
AB - Identifying who, among problem drinkers, is best suited for moderation and has
the greatest likelihood to control drinking has important public health
implications. The current study aimed to identify profiles of problem drinkers
who may be more or less successful in moderating drinking within the context of a
randomized clinical trial of a brief treatment for alcohol use disorder. A person
centered approach was implemented, utilizing composite, baseline daily diary
values of confidence and commitment to reduce drinking. Problem drinkers (N = 89)
were assessed, provided feedback about their drinking, and randomly assigned to 1
of 3 conditions: 2 brief alcohol use disorder treatments or a third group asked
to change on their own. Global self-report assessments were administered at
baseline and Week 8 (end of treatment). Daily diary composites were created from
data collected via an interactive voice recording system during the week prior to
baseline. A K-means cluster analysis identified 3 groups: high, moderate, and low
confidence and commitment to change drinking. Group differences were explored,
and then group membership was entered into generalized estimating equations to
predict drinking trajectories over time. Findings revealed that the groups
differentially reduced their drinking, such that the high group had greater
reduction in drinking and a faster rate of reduction than the other 2 groups, and
the moderate group had greater reduction than the low group. Findings suggest
that baseline motivation and self-efficacy are important for predicting prognoses
related to successful moderated drinking. Limitations and arenas for future
research are discussed.
PMID- 25134035
TI - Protective behavioral strategies, alcohol expectancies, and drinking motives in a
model of college student drinking.
AB - An extensive body of research asserts alcohol expectancies, or beliefs regarding
the effects of alcohol, as an important influence on drinking. However, the
extent to which expectancies are related to drinking motives and protective
behavioral strategies (PBS) has yet to be examined. Existing alcohol mediational
models suggest associations between expectancies and drinking motives as well as
positive drinking motives and PBS use. Thus, it is possible that drinking motives
and PBS use act as intervening factors in the relationship between expectancies
and alcohol outcomes. Consequently, the cross-sectional study presented here
aimed to test the indirect effect of expectancies (i.e., social facilitation) on
alcohol outcomes through drinking motives and PBS use. Participants were 520 (358
female) college student drinkers with a mean age of 20.80 (SD = 4.61) years.
Students completed measures of expectancies, drinking motives, PBS use, alcohol
use, and alcohol-related problems. Results from structural equation modeling
indicated that drinking motives and PBS mediated the relationship between social
expectancies and alcohol use. In particular, expectancies were associated with
greater positive drinking motives, drinking motives were associated with less PBS
use, and PBS was associated with less alcohol use and fewer alcohol-related
problems. Given the key role of PBS in explaining drinking outcomes in our model,
active efforts to incorporate PBS in alcohol interventions may be particularly
beneficial for college students. Further, our findings support the consideration
of PBS use as a part of the motivational model of alcohol use in future work.
PMID- 25134036
TI - An examination of college student activities and attentiveness during a web
delivered personalized normative feedback intervention.
AB - Both heavy drinking and related risky sexual behavior among college students are
common and are often associated with a number of negative consequences. A
previously reported randomized controlled trial showed that a brief personalized
normative feedback (PNF) intervention reduced the alcohol consumption and alcohol
related risky sexual behavior of heavy drinking, sexually active college students
(Lewis et al., 2014). For the present study, we examined what activities students
were engaged in when viewing the feedback, as well as who they were with and
where they were when receiving the intervention. Furthermore, we conducted
supplemental analyses with perceived attentiveness as a hypothesized predictor of
change using the same sample (N = 480). Findings indicated that most students
were engaged in activities when viewing the feedback and that most students
viewed the feedback alone and at home. Furthermore, results revealed PNF to be
most effective in reducing drinks per week among participants who reported
greater attention. Clinical implications and suggestions for additional research
examining how attentiveness can be increased during Web-based interventions are
discussed.
PMID- 25134037
TI - The influence of self-exempting beliefs and social networks on daily smoking: a
mediation relationship explored.
AB - The decision to initiate, maintain, or quit cigarette smoking is structured by
both social networks and health beliefs. Self-exempting beliefs affect people's
decisions in favor of a behavior even when they recognize the harm associated
with it. This study incorporated the literatures on social networks and self
exempting beliefs to study the problem of daily smoking by exploring their
mediatory relationships and the mechanisms of how smoking behavior is developed
and maintained. Specifically, this article hypothesizes that social networks
affect daily smoking directly as well as indirectly by facilitating the formation
of self-exempting beliefs. The sample comes from urban male residents in
Hangzhou, China randomly selected and interviewed through multistage sampling in
2011. Using binary mediation analysis with logistic regression to test the
hypotheses, the authors found that (a) daily smoking is associated with having
smokers in several social network arenas and (b) self-exempting beliefs about
smoking mediate the association between coworker network and daily smoking, but
not for family network and friend network. The role of social network at work
place in the creation and maintenance of self-exempting beliefs should be
considered by policymakers, prevention experts, and interventionists.
PMID- 25134039
TI - The validity of different measures of automatic alcohol action tendencies.
AB - Previous studies have demonstrated that automatic alcohol action tendencies are
related to alcohol consumption and hazardous drinking. These action tendencies
are measured with reaction time tasks in which the latency to make an approach
response to alcohol pictures is compared with the latency to make an avoidance
response. In the literature, 4 different tasks have been used, and these tasks
differ on whether alcohol is a relevant (R) or irrelevant (IR) feature for
categorization and on whether participants must make a symbolic approach response
(stimulus-response compatibility [SRC] tasks) or an overt behavioral response
(approach avoidance tasks [AAT]) to the pictures. Previous studies have shown
positive correlations between measures of action tendencies and hazardous
drinking and weekly alcohol consumption. However, results have been inconsistent
and the different measures have not been directly compared with each other.
Therefore, it is unclear which task is the best predictor of hazardous drinking
and alcohol consumption. In the present study, 80 participants completed all 4
measures of action tendencies (i.e., R-SRC, IR-SRC, R-AAT, and IR-AAT) and
measures of alcohol consumption and hazardous drinking. Stepwise regressions
showed that the R-SRC and R-AAT were the only significant predictors of hazardous
drinking, whereas the R-AAT was the only reliable predictor of alcohol
consumption. Our results confirm that drinking behavior is positively correlated
with automatic alcohol approach tendencies, but only if alcohol-relatedness is
the relevant feature for categorization. Theoretical implications and
methodological issues are discussed. (PsycINFO Database Record
PMID- 25134038
TI - Applying an ensemble classification tree approach to the prediction of completion
of a 12-step facilitation intervention with stimulant abusers.
AB - The purpose of this study was to explore the selection of predictor variables in
the evaluation of drug treatment completion using an ensemble approach with
classification trees. The basic methodology is reviewed, and the subagging
procedure of random subsampling is applied. Among 234 individuals with stimulant
use disorders randomized to a 12-step facilitative intervention shown to increase
stimulant use abstinence, 67.52% were classified as treatment completers. A total
of 122 baseline variables were used to identify factors associated with
completion. The number of types of self-help activity involvement prior to
treatment was the predominant predictor. Other effective predictors included
better coping self-efficacy for substance use in high-risk situations, more days
of prior meeting attendance, greater acceptance of the Disease model, higher
confidence for not resuming use following discharge, lower Addiction Severity
Index (ASI) Drug and Alcohol composite scores, negative urine screens for cocaine
or marijuana, and fewer employment problems. The application of an ensemble
subsampling regression tree method utilizes the fact that classification trees
are unstable but, on average, produce an improved prediction of the completion of
drug abuse treatment. The results support the notion there are early indicators
of treatment completion that may allow for modification of approaches more
tailored to fitting the needs of individuals and potentially provide more
successful treatment engagement and improved outcomes.
PMID- 25134040
TI - Does DSM-5 nomenclature for inhalant use disorder improve upon DSM-IV?
AB - Among drug classes, substance use disorder (SUD) consequent to using inhalants
(SUD-I) has perhaps the smallest evidence base. This study compared DSM-IV versus
DSM-5 nomenclatures, testing whether 4 traditional categories of inhalants
(aerosols, gases, nitrites, solvents) are manifestations of a single pathology,
obtaining item parameters of SUD-I criteria, and presenting evidence that SUD can
result from using nitrites. An urban, Midwestern, community sample of 162
inhalant users was recruited. Participants were 2/3 male, nearly 85% White, and
had a mean age of 20.3 years (SD = 2.4 years), spanning the ages of greatest
incidence of SUD and slightly older than the primary ages of inhalants use
initiation. Analyses consisted of bivariate associations, principle components
analysis, and item response theory analysis. Validity was demonstrated for SUD-I
consequent to each inhalant type as well as for aggregating all inhalant types
into a single drug class. Results supported DSM-5 nomenclature over DSM-IV in
multiple ways except that occurrence of diagnostic orphans was not statistically
smaller using DSM-5. (PsycINFO Database Record
PMID- 25134041
TI - The diversion of stimulant medications among a convenience sample of college
students with current prescriptions.
AB - Diversion is defined as the unlawful channeling of regulated pharmaceuticals from
legal sources to the illicit marketplace. Persons with legal prescriptions often
give away or sell their medications to others. The misuse of prescription
stimulant medications continues to be a problem on college campuses and a need to
understand how students are obtaining stimulant medications exists. The object of
the study was to identify the prevalence, correlates, and motivations associated
with diversion of prescription stimulants among current prescription holders. A
large sample of undergraduates (n = 1,022) between the ages of 18 and 24 enrolled
at a large public university in the southeastern United States completed an in
class questionnaire. Among those respondents, we identified 151 current stimulant
prescription holders and analyzed the prevalence, motivations, and correlates
associated with lifetime and current diversion. Overall, 58.9% of current
prescription holders had given away or sold their stimulant medication during
their lifetime. Those with a history of nonmedical use of prescription stimulants
were almost 5 times more likely to divert their medication during their lifetime.
The majority of those engaging in lifetime and current diversion medication did
so infrequently. The most common motivations reported for both lifetime and
current diversion were "to make extra money" and to "help during a time of high
academic stress." Students who reported a history of prescription misuse were
also more likely to engage in current diversion. Diversion-related behaviors
should be explored further and programs aimed at the reducing these behaviors
should be considered.
PMID- 25134042
TI - Associations between childhood adversity, adult stressful life events, and past
year drug use disorders in the National Epidemiological Study of Alcohol and
Related Conditions (NESARC).
AB - Stress sensitization, whereby CA lowers tolerance to later stressors, has been
proposed as a potential mechanism explaining the association between exposure to
childhood adversities (CA) and drug use disorders in adulthood. However, this
mechanism remains untested. This paper begins to address this gap through
exploring associations between CA exposure and stressful events in adulthood for
predicting drug use disorders. We used data drawn from Wave 2 of the U.S.
National Epidemiological Survey of Alcohol and Related Conditions (n = 34,653) to
explore whether the association between past-year stressful life events and the
12-month prevalence of disordered cannabis, stimulant, and opiate use varied by
the number of types of CA that an individual was exposed to. Past-year stressful
life events were associated with an increased risk of cannabis, stimulant, and
opiate use disorders among men and women. Exposure to CA was associated with
increased risk for disordered cannabis use among men and women and opiate use
among men only. Finally, we found significant associations between exposure to CA
and past-year stressful life events in predicting disordered drug use, but only
for women in relation to disordered stimulant and opiate use. Findings are
suggestive of possible stress sensitization effects in predicting disordered
stimulant and opiate use among women. Implications of these findings for the
prevention and treatment of drug use disorders and for future research are
discussed.
PMID- 25134043
TI - Assessing sexual motives for drinking alcohol among HIV-positive men who have sex
with men.
AB - Individuals who drink alcohol for the explicit motive of facilitating or
enhancing sex may be more likely to engage in risky sexual behavior, including
having sex under the influence of alcohol. However, efforts to assess sexual
motives for drinking (SMDs) have been very limited to date. We examined the
psychometric properties of a 5-item measure of SMDs in a sample of HIV-positive
heavy drinking men who have sex with men. Findings provided excellent support for
the scale's internal consistency and concurrent validity with a well-established
measure of sexual alcohol expectancies (SAEs). Good discriminant validity was
also established, as SMDs were correlated with other drinking motives but
uniquely predicted the proportion of sex acts occurring under the influence of
alcohol and other drugs, over and above other drinking motives and SAEs. SMDs
were not significantly associated with unprotected anal intercourse. Adjusting
for alcohol problem severity, higher SMDs were associated with lower willingness
to consider changing drinking. Results suggest this measure of SMDs exhibits
sound psychometric properties and may be useful in studies examining the
association between alcohol use and sexual behavior. (PsycINFO Database Record
PMID- 25134045
TI - Implicit identification with drug and alcohol use predicts retention in
residential rehabilitation programs.
AB - Research has identified numerous factors associated with successful treatment in
alcohol and drug rehabilitation programs, yet treatment completion rates are
often low and subsequent relapse rates very high. We propose that people's
implicit identification with drugs and alcohol may be an additional factor that
impacts their ability to complete abstinence-based rehabilitation programs. In
the current research, we measured implicit identification with drugs and alcohol
using the Implicit Association Test (Greenwald, McGhee, & Schwartz, 1998) among
137 members of a residential rehabilitation program for drugs and alcohol (104
men; mean age = 35 years old, 47 of whom were court-ordered to attend). Implicit
identification with drugs and alcohol was measured within 1 week of arrival and
again 3 weeks later, prior to the onset of the treatment phase of the program.
Duration in rehabilitation was assessed 1 year later. Consistent with
predictions, implicit identification with drugs and alcohol predicted the
duration that people remained in residential rehabilitation even though a self
report measure of identification with drugs and alcohol did not. These results
suggest that implicit identification with drugs and alcohol might be an important
predictor of treatment outcomes, even among those with serious problems with drug
and alcohol use. (PsycINFO Database Record
PMID- 25134046
TI - Drinking motives and attentional bias to affective stimuli in problem and non
problem drinkers.
AB - Problem drinking may reflect a maladaptive means of coping with negative emotions
or enhancing positive emotions. Disorders with affective symptoms are often
characterized by attentional biases for symptom-congruent emotionally valenced
stimuli. Regarding addictions, coping motivated (CM) problem gamblers exhibit an
attentional bias for negative stimuli, whereas enhancement motivated (EM) problem
gamblers exhibit this bias for positive stimuli (Hudson, Jacques, & Stewart,
2013). We predicted that problem drinkers would show similar motive-congruent
attentional biases. Problem and non-problem drinkers (n = 48 per group) completed
an emotional orienting task measuring attentional biases to positive, negative,
and neutral stimuli. As predicted, EM problem drinkers showed an attentional bias
for positive information (i.e., reduced accuracy for positively cued trials).
However, CM problem drinkers displayed a general distractibility (i.e., reduced
accuracy, regardless of cue valence). The results add further support for Cooper
et al.'s (1992) motivational model of alcohol use, and indicate potential
motivation-matched intervention targets. (PsycINFO Database Record
PMID- 25134044
TI - A retrospective analysis of dissemination biases in the brief alcohol
intervention literature.
AB - This study examined dissemination and reporting biases in the brief alcohol
intervention literature. We used retrospective data from 179 controlled trials
included in a meta-analysis on brief alcohol interventions for adolescents and
young adults. We examined whether the magnitude and direction of effect sizes
were associated with publication type, identification source, language, funding,
time lag between intervention and publication, number of reports, journal impact
factor, and subsequent citations. Results indicated that effect sizes were larger
for studies that had been funded (b = 0.14, 95% confidence interval [CI] [0.04,
0.23]), had a shorter time lag between intervention and publication (b = -0.03,
95% CI [-0.05, -.001]), and were cited more frequently (b = 0.01, 95% CI [+0.00,
0.01]). Studies that were cited more frequently by other authors also had greater
odds of reporting positive effects (odds ratio = 1.10, 95% CI [1.02, 1.18]).
Results indicated that time lag bias has increased recently: Larger and positive
effect sizes were published more quickly in recent years. We found no evidence,
however, that the magnitude or direction of effects was associated with location
source, language, or journal impact factor. We conclude that dissemination biases
may indeed occur in the social and behavioral science literature, as has been
consistently documented in the medical literature. As such, primary researchers,
journal reviewers, editors, systematic reviewers, and meta-analysts must be
cognizant of the causes and consequences of these biases, and commit to engage in
ethical research practices that attempt to minimize them. (PsycINFO Database
Record
PMID- 25134047
TI - Employment-based reinforcement of adherence to oral naltrexone in unemployed
injection drug users: 12-month outcomes.
AB - Oral naltrexone could be a promising relapse-prevention pharmacotherapy for
recently detoxified opioid-dependent patients; however, interventions are often
needed to promote adherence with this treatment approach. We recently conducted a
study to evaluate a 26-week employment-based reinforcement intervention of oral
naltrexone in unemployed injection drug users (Dunn et al., 2013). Participants
were randomly assigned into a contingency (n = 35) group required to ingest
naltrexone under staff observation to gain entry into a therapeutic workplace or
a prescription (n = 32) group given a take-home supply of oral naltrexone and
access to the workplace without observed ingestion. Monthly urine samples were
collected and analyzed for evidence for naltrexone adherence, opioid use, and
cocaine use. As previously reported, contingency participants provided
significantly more naltrexone-positive urine samples than prescription
participants during the 26-week intervention period. The goal of this current
study is to report the 12-month outcomes, which occurred 6 months after the
intervention ended. Results at the 12-month visit showed no between-groups
differences in naltrexone-positive, opioid-negative, or cocaine-negative urine
samples and no participant self-reported using naltrexone at the follow-up visit.
These results show that even after a period of successfully reinforced oral
naltrexone adherence, longer-term naltrexone use is unlikely to be maintained
after reinforcement contingencies are discontinued. (PsycINFO Database Record
PMID- 25134048
TI - Couples' marijuana use is inversely related to their intimate partner violence
over the first 9 years of marriage.
AB - Research on the association between marijuana use and intimate partner violence
(IPV) has generated inconsistent findings, and has been primarily based on cross
sectional data. We examined whether husbands' and wives' marijuana use predicted
both husbands' and wives' IPV perpetration over the first 9 years of marriage
(Wave 1, n = 634 couples). We also examined moderation by antisocial behavior,
the spouse's marijuana use, and whether IPV was reported during the year before
marriage. These predictive associations were calculated using a time-lagged
multivariate generalized multilevel model, simultaneously estimating predictors
of husband and wife IPV. In fully adjusted models, we found that more frequent
marijuana use by husbands and wives predicted less frequent IPV perpetration by
husbands. Husbands' marijuana use also predicted less frequent IPV perpetration
by wives. Moderation analyses demonstrated that couples in which both spouses
used marijuana frequently reported the least frequent IPV perpetration. There was
a significant positive association between wives' marijuana use and wives' IPV
perpetration, but only among wives who had already reported IPV perpetration
during the year before marriage. These findings suggest there may be an overall
inverse association between marijuana use and IPV perpetration in newly married
couples, although use may be associated with greater risk of perpetration among
women with a history of IPV perpetration.
PMID- 25134049
TI - Reported planning before and after quitting and quit success: retrospective data
from the ITC 4-Country Survey.
AB - Planning before quitting smoking is widely believed to be beneficial and is
usually recommended in cessation counseling, but there is little evidence on the
efficacy of specific planning activities. Using data from 1140 respondents who
reported quit attempts at Wave 8 of the ITC 4-Country Survey, we analyzed use of
8 specific planning strategies before (5) and after (3) implementation of a quit
attempt, in relation to cessation outcomes, delay in implementation of the
attempt, and recent quitting history. Most participants reported some planning
both before and after quitting, even among those reporting quitting
'spontaneously.' Younger smokers, those who cut down before quitting, and users
of stop-smoking medication were more likely to report planning. Those who planned
prequit were also more likely to plan postquit. Unexpectedly, we found no clear
benefit of planning on short-term (1 month) cessation outcomes, whereas one
prequit strategy (practicing not smoking) was negatively related to outcome.
There was evidence for a predicted moderating effect of recent quitting
experience on planning for the prequit task 'practice replacement strategies.'
This predicted quit success among those with multiple quit attempts in the past
year, but failure among those without. This finding suggests that the quality of
planning may be critical. More research, particularly on the moderating effect of
quit experience, and where measures of planning are collected before outcomes
become evident, is needed before clear recommendations can be made on the utility
of various forms of planning for the success of quit attempts.
PMID- 25134050
TI - Sexual-orientation disparities in substance use in emerging adults: a function of
stress and attachment paradigms.
AB - More lesbian, gay, and bisexual (LGB) youths than heterosexuals report substance
use. We examined a theoretical model to understand these disparities in lifetime
and past-year substance use by means of stress and attachment paradigms, using
the longitudinal Growing Up Today Study (GUTS) and Nurses' Health Study II
(NHSII). GUTS participants are the children of participants in NHSII; thus, child
and maternal data are available. In addition, GUTS contains siblings, allowing
for comparisons of LGB and heterosexual siblings. Of 5,647 GUTS youths (M = 20.6
years old in 2005), 1.6% were lesbian/gay (LG), 1.6% bisexual (BI), 9.9% mostly
heterosexual (MH), and 86.9% completely heterosexual (CH). After adjusting for
sibling clustering in GUTS and covariates, significantly more sexual minorities
(LGs, BIs, and MHs) than CHs reported lifetime and past-year smoking,
nonmarijuana illicit drug use, and prescription drug misuse. More sexual
minorities also reported marijuana use in the past year. The relations between
sexual orientation and substance use were moderated by the stress markers: As
mother's discomfort with homosexuality increased, more BIs and MHs than CHs used
substances. As childhood gender nonconforming behaviors increased, more LGs than
CHs used substances. The relations between sexual orientation and substance use
were mediated by attachment and maternal affection (percent of effect mediated
ranged from 5.6% to 16.8%% for lifetime substance use and 4.9% to 24.5% for past
year use). In addition, sibling comparisons found that sexual minorities reported
more substance use, more childhood gender nonconforming behaviors, and less
secure attachment than CH siblings; mothers reported less affection for their
sexual minority than CH offspring. The findings indicate the importance of stress
and attachment paradigms for understanding sexual-orientation disparities in
substance use.
PMID- 25134051
TI - Application of item response theory to tests of substance-related associative
memory.
AB - A substance-related word-association test (WAT) is one of the commonly used
indirect tests of substance-related implicit associative memory and has been
shown to predict substance use. This study applied an item response theory (IRT)
modeling approach to evaluate psychometric properties of the alcohol- and
marijuana-related WATs and their items among 775 ethnically diverse at-risk
adolescents. After examining the IRT assumptions, item fit, and differential item
functioning (DIF) across gender and age groups, the original 18 WAT items were
reduced to 14 and 15 items in the alcohol- and marijuana-related WAT,
respectively. Thereafter, unidimensional one- and two-parameter logistic models
(1PL and 2PL models) were fitted to the revised WAT items. The results
demonstrated that both alcohol- and marijuana-related WATs have good psychometric
properties. These results were discussed in light of the framework of a unified
concept of construct validity (Messick, 1975, 1989, 1995).
PMID- 25134052
TI - Drinking to cope among African American college students: an assessment of
episode-specific motives.
AB - Despite evidence that African Americans are disproportionately affected by
drinking to cope relative to European Americans, African American college
students' drinking motives remain understudied. Additionally, most research has
only examined between-person differences in drinking to cope as a predictor of
alcohol use, ignoring within-person variability. In the current daily diary study
of 462 African American undergraduates from a historically Black university,
associations between episode-specific drinking to cope motives and alcohol use
were tested, an approach more consistent with motivational theories of drinking.
At baseline, students completed traditional global drinking motive measures; then
for 30 days they reported the number of standard drinks they consumed the
previous night, and, if they drank, their coping, enhancement, and social reasons
for doing so. Students who reported higher mean levels of episode-specific coping
motives, on average, consumed more alcohol on drinking evenings. Furthermore,
mean episode-specific coping motives, but not global coping motives, predicted
average levels of alcohol use. Additionally, coping motives were particularly
important for predicting nonsocial (vs. social) drinking. Finally, during
evenings for which students reported higher than usual episode-specific coping
motives, men consumed more alcohol in both social and nonsocial contexts; in
contrast, women reporting higher than usual drinking-to-cope motives only
consumed more nonsocial drinks. In conclusion, drinking among African American
college students was related to coping motives, particularly among men and in the
context of nonsocial alcohol consumption. Moreover, motivational theories of
alcohol use may be refined by measuring episode-specific drinking motives that
more accurately capture the drinking-to-cope process.
PMID- 25134054
TI - The relationship between craving and tobacco use behavior in laboratory studies:
a meta-analysis.
AB - Published laboratory studies from the last 50 years that included measures of
craving and tobacco-consumption or tobacco-seeking measures were included in a
meta-analysis in order to assess the relationship between craving and tobacco
use. Seeking measures were further subdivided into those that reflected control
by nonautomatic and automatic cognitive processes. Of 2,498 articles identified
by the initial literature review, 204 analyses from 50 studies were deemed
eligible. Overall, the relationship between craving and outcome behaviors was
modest (r = .20, p < .001). Studies that imposed abstinence during data
collection showed a stronger relationship between craving and outcome (r = .24, p
< .001) than studies that did not (r = .18, p < .001). Further, of those studies
that reported dependence, the overall association between craving and outcome was
stronger for smokers who were less dependent. Separate meta-analyses revealed
that the type of outcome measure moderated the omnibus effect, with the
relationship between craving and nonautomatic seeking measures (r = .34, p <
.001) being stronger than the relationship between craving and automatic
seeking/consumption measures (both rs = 0.15, p < .001). These findings suggest
that craving may play a role in, but does not fully account for, tobacco-use
behaviors; furthermore, the extent to which craving predicts behavior may be
increased when the behavior is under nonautomatic cognitive control.
PMID- 25134053
TI - Psychiatric correlates of injection risk behavior among young people who inject
drugs.
AB - People who inject drugs (PWID) and have mental health conditions, such as major
depression, an anxiety disorder, or antisocial or borderline personality
disorder, may have elevated risk for HIV and HCV infection. This study examined
the associations between psychiatric disorders and risky injection behavior in an
out-of-treatment sample of young PWID. We recruited participants through outreach
and respondent-driven sampling (RDS). Participants completed a computer-assisted
self-interview and a psychiatric interview. Interviews took place at a community
based field site of the Community Outreach Intervention Projects. Participants
were 570 young adults (18 to 25 years) who injected drugs in the previous 30
days. Psychiatric diagnoses were based on interviews using the Psychiatric
Research Interview for Substance and Mental Disorders (PRISM). Injection behavior
was classified into 3 categories: receptive syringe sharing, other equipment
sharing only, and no sharing. Associations between injection risk behavior and
psychiatric diagnoses were tested using RDS-weighted multinomial regressions.
Substance-induced lifetime and past-year major depression, and borderline
personality disorder, were significantly associated with a greater likelihood of
receptive syringe sharing (p < .001). Substance-induced major depression in the
past year was also associated with nonsyringe equipment sharing (p < .01).
Primary major depression, antisocial personality disorder, and anxiety disorders
other than posttraumatic stress disorder were slightly more prevalent among
injectors who shared syringes; however, the associations were not statistically
significant. Substance-induced major depression and borderline personality
disorder are common among young PWID and are associated with risky injection
behavior.
PMID- 25134055
TI - Translation of associative learning models into extinction reminders delivered
via mobile phones during cue exposure interventions for substance use.
AB - Despite experimental findings and some treatment research supporting the use of
cues as a means to induce and extinguish cravings, interventions using cue
exposure have not been well integrated into contemporary substance abuse
treatments. A primary problem with exposure-based interventions for addiction is
that after learning not to use substances in the presence of addiction cues
inside the clinic (i.e., extinction), stimuli in the naturalistic setting outside
the clinic may continue to elicit craving, drug use, or other maladaptive
conditioned responses. For exposure-based substance use interventions to be
efficacious, new approaches are needed that can prevent relapse by directly
generalizing learning from the therapeutic setting into naturalistic settings
associated with a high risk for relapse. Basic research suggests that extinction
reminders (ERs) can be paired with the context of learning new and more adaptive
conditioned responses to substance abuse cues in exposure therapies for
addiction. Using mobile phones and automated dialing and data collection
software, ERs can be delivered in everyday high-risk settings to inhibit
conditioned responses to substance-use-related stimuli. In this review, we
describe how associative learning mechanisms (e.g., conditioned inhibition) can
inform how ERs are conceptualized, learned, and implemented to prevent substance
use when delivered via mobile phones. This approach, exposure with portable
reminders of extinction, is introduced as an adjunctive intervention that uses
brief automated ERs between clinic visits when individuals are in high-risk
settings for drug use.
PMID- 25134057
TI - The role of avoidance and inflexibility in characterizing response to contingency
management for cocaine use disorders: A secondary profile analysis.
AB - Contingency management (CM) is a reinforcement-based approach that provides
tangible rewards for objectively verified drug abstinence. CM is the most
effective available behavioral intervention for cocaine use disorders; however,
response to CM is variable, with significant rates of nonresponse. In the present
investigation, we conducted a secondary profile analysis to identify potentially
modifiable cognitive-affective characteristics associated with CM response
(abstinence vs. continued use) preceding a pharmacotherapy trial for cocaine
dependence. Ninety-nine cocaine-dependent, treatment-seeking adults participated
in a 4-week baseline CM procedure using high-value vouchers for submission of
cocaine-negative urines. Separate profiles for responders and the nonresponders
were established using standardized mean scores on relevant pretreatment measures
of negative affect, experiential avoidance, cocaine withdrawal/craving, and
impulsivity. Results indicated no differences between responder subgroups on
baseline levels of negative affect, withdrawal/craving, or impulsivity; however,
CM nonresponders, relative to responders, reported significantly higher levels of
avoidance and behavioral inflexibility (p < .01) in the context of distressing
cocaine-related thoughts, feelings, and bodily sensations. These data suggest
that emotion regulation skills may serve as a therapeutic strategy for enhancing
response to CM for cocaine use disorders. (PsycINFO Database Record
PMID- 25134056
TI - The relationship of therapeutic alliance and treatment delivery fidelity with
treatment retention in a multisite trial of twelve-step facilitation.
AB - This study examined associations of therapeutic alliance and treatment delivery
fidelity with treatment retention in Stimulant Abusers to Engage in Twelve-Step
(STAGE-12), a community-based trial of 12-Step Facilitation (TSF) conducted
within the National Drug Abuse Treatment Clinical Trials Network (CTN). The STAGE
12 trial randomized 234 stimulant abusers enrolled in 10 outpatient drug
treatment programs to an eight-session, group and individual TSF intervention.
During the study, TSF participants rated therapeutic alliance using the Helping
Alliance questionnaire-II. After the study, independent raters evaluated
treatment delivery fidelity of all TSF sessions on adherence, competence, and
therapist empathy. Poisson regression modeling examined relationships of
treatment delivery fidelity and therapeutic alliance with treatment retention
(measured by number of sessions attended) for 174 participants with complete
fidelity and alliance data. Therapeutic alliance (p = .005) and therapist
competence (p = .010) were significantly associated with better treatment
retention. Therapist adherence was associated with poorer retention in a
nonsignificant trend (p = .061). In conclusion, stronger therapeutic alliance and
higher therapist competence in the delivery of a TSF intervention were associated
with better treatment retention whereas treatment adherence was not. Training and
fidelity monitoring of TSF should focus on general therapist skills and
therapeutic alliance development to maximize treatment retention. (PsycINFO
Database Record
PMID- 25134058
TI - Testing the four-factor model of personality vulnerability to alcohol misuse: a
three-wave, one-year longitudinal study.
AB - The 4-factor model of personality vulnerability identifies 4 personality risk
factors for alcohol misuse: hopelessness, anxiety sensitivity, impulsivity, and
sensation seeking. These personality traits are associated with distinct
mechanisms and motivations for alcohol misuse. Individuals high in hopelessness
drink to regulate dysphoric affect, while those high in anxiety sensitivity drink
to reduce anxiety and to conform to peer expectations. Individuals high in
sensation seeking are highly sensitive to the rewarding properties of alcohol,
and misuse alcohol to maximize enjoyment. Impulsivity is a broad risk factor
contributing to all drinking motives. We hypothesized that personality
vulnerabilities would indirectly predict alcohol quantity and problems through
specific drinking motives theorized by the 4-factor model. The present study
tested hypotheses using a 3-wave, 1-year longitudinal study of undergraduate
drinkers (N = 302). Data were analyzed using multilevel path analysis.
Hopelessness and impulsivity were positively related to drinking motives in the
expected fashion. Anxiety sensitivity was related to coping-anxiety and
conformity motives only in the between-subjects model (partially supporting
hypotheses), while sensation seeking was generally unrelated to all drinking
motives and alcohol outcomes (failing to support hypotheses). Enhancement motives
predicted alcohol quantity and problems at both levels, coping-depression motives
predicted alcohol problems at the between-subjects level only, and coping
anxiety, conformity, and social motives failed to predict alcohol outcomes beyond
other motives. Overall, this study partially supports the 4-factor model, with
the strongest support emerging for impulsivity and hopelessness. This study
suggests that personality traits such as impulsivity and hopelessness may be
important targets in prevention and treatment with undergraduate drinkers.
PMID- 25134059
TI - Personality and gambling involvement: a person-centered approach.
AB - Individual differences in personality are likely to play an important role in
explaining the propensity to gamble. One of the potential roadblocks to
elucidating the relation between personality and gambling may be inadequately
accounting for the diversity of gambling activities. The goal of the present
study was to provide a comprehensive and nuanced portrait of the relation between
personality and gambling by taking a multivariate approach to the co-use of
multiple gambling activities and employing a broad inventory of potentially
relevant personality dimensions. Participants were 4,669 individuals from a
national Australian twin registry. Structured interviews including an extensive
assessment of gambling behaviors were conducted, and personality questionnaires
that included the Multidimensional Personality Questionnaire, the Sensation
Seeking Scale, and the Magical Ideation Scale were completed. A latent class
analysis of past-year involvement in 10 different gambling activities was
performed to classify the participants into 5 groups. Unique personality
configurations characterized the 3 more gambling-involved latent classes: (a) low
behavioral control in the context of high negative emotionality and magical
thinking typified extensive, versatile gamblers at high risk of gambling
problems; (b) average behavioral control in the context of high negative
emotionality and magical thinking typified those who primarily gambled on non
strategic games of chance; (c) low behavioral control in the context of high
positive emotionality and low magical ideation typified those who primarily
gambled on strategic games of skill. This study illustrates the value of using a
multivariate person-centered approach for characterizing the personality
correlates of the multifaceted phenomenon that is gambling.
PMID- 25134061
TI - Swelling of polyelectrolyte and polyzwitterion brushes by humid vapors.
AB - Swelling behavior of polyelectrolyte and polyzwitterion brushes derived from
poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) in water vapor is
investigated using a combination of neutron and X-ray reflectivity and
spectroscopic ellipsometry over a wide range of relative humidity (RH) levels.
The extent of swelling depends strongly on the nature of the side-chain
chemistry. For parent PDMAEMA, there is an apparent enrichment of water vapor at
the polymer/air interface. Despite extensive swelling at high humidity level, no
evidence of charge repulsion is found in weak or strong polyelectrolyte brushes.
Polyzwitterionic brushes swell to a greater extent than the quaternized brushes
studied. However, for RH levels beyond 70%, the polyzwitterionic brushes take up
less water molecules, leading to a decline in water volume fraction from the
maximum of ~0.30 down to ~0.10. Using a gradient in polymer chain grafting
density (sigma), we provide evidence that this behavior stems from the formation
of inter- and intramolecular zwitterionic complexes.
PMID- 25134062
TI - Clearing common bile duct stones: one size does not fit all.
PMID- 25134063
TI - Extrinsic and intrinsic charge trapping at the graphene/ferroelectric interface.
AB - The interface between graphene and the ferroelectric superlattice PbTiO3/SrTiO3
(PTO/STO) is studied. Tuning the transition temperature through the PTO/STO
volume fraction minimizes the adorbates at the graphene/ferroelectric interface,
allowing robust ferroelectric hysteresis to be demonstrated. "Intrinsic" charge
traps from the ferroelectric surface defects can adversely affect the graphene
channel hysteresis and can be controlled by careful sample processing, enabling
systematic study of the charge trapping mechanism.
PMID- 25134060
TI - The renal dopaminergic system: novel diagnostic and therapeutic approaches in
hypertension and kidney disease.
AB - Salt sensitivity of blood pressure, whether in hypertensive or normotensive
subjects, is associated with increased cardiovascular risk and overall mortality.
Salt sensitivity can be treated by reducing NaCl consumption. However, decreasing
salt intake in some may actually increase cardiovascular risk, including an
increase in blood pressure, that is, inverse salt sensitivity. Several genes have
been associated with salt sensitivity and inverse salt sensitivity. Some of these
genes encode proteins expressed in the kidney that are needed to excrete a sodium
load, for example, dopamine receptors and their regulators, G protein-coupled
receptor kinase 4 (GRK4). We review here research in this field that has provided
several translational opportunities, ranging from diagnostic tests to gene
therapy, such as (1) a test in renal proximal tubule cells isolated from the
urine of humans that may determine the salt-sensitive phenotype by analyzing the
recruitment of dopamine D1 receptors to the plasma membrane; (2) the presence of
common GRK4 gene variants that are not only associated with hypertension but may
also be predictive of the response to antihypertensive therapy; (3) genetic
testing for polymorphisms of the dopamine D2 receptor that may be associated with
hypertension and inverse salt sensitivity and may increase the susceptibility to
chronic kidney disease because of loss of the antioxidant and anti-inflammatory
effects of the renal dopamine D2 receptor, and (4) in vivo renal selective
amelioration of renal tubular genetic defects by a gene transfer approach, using
adeno-associated viral vectors introduced to the kidney by retrograde ureteral
infusion.
PMID- 25134064
TI - Tricyclic pyrazoles part 7. Discovery of potent and selective
dihydrothienocyclopentapyrazole derived CB2 ligands.
AB - A series of dihydrothienocyclopentapyrazole-based derivatives was synthesized and
evaluated for the affinity at CB1 and CB2 receptors. The major term, the 6-methyl
1-(1,4-dichlorophenyl)-N-piperidinyl)-1,4-dihydrothieno[2',3'-4,5]cyclopenta[1,2
c]pyrazole-3-carboxamide (6a), displayed a high affinity and good selectivity for
CB2 receptors (Ki values of 2.30 nM for CB2 receptor and 440 nM for CB1 receptors
respectively). Subsequent analogue preparation resulted in the identification of
compounds such as 6b, 6d, 6e, 6k, 6l, 6m, 6s and 6t that showed 1.3-485 fold
selectivity for CB2 receptors with potencies in the 1.1-7.2 nM range. These
compounds profiled as full agonists at CB2 receptor in an inhibition assay of P
ERK 1/2 up regulation in HL-60 cells.
PMID- 25134065
TI - Time-resolved spectroscopic and density functional theory study of the
photochemistry of Irgacure-2959 in an aqueous solution.
AB - The photocleavage reaction mechanism of 2-hydroxy-4'-(2-hydroxyethoxy)-2
methylpropiophenone (Irgacure-2959) was investigated using femtosecond (fs) and
nanosecond (ns) transient absorption (-TA) spectroscopy and also picosecond (ps)
and nanosecond (ns) time-resolved resonance Raman (-TR(3)) spectroscopy
experiments in a water-rich (volume ratio of acetonitrile/water = 3:7) solution.
TA spectroscopy was used to study the dynamics of the benzoyl radical growth and
decay as well as to investigate the radical quenching process by the radical
scavenger methyl acrylate. ps- and ns-TR(3) spectroscopies were employed to
monitor the formation of the benzoyl radical and also to characterize its
electronic and structural properties. The fs-TA experiments results indicate that
the Irgacure-2959 lowest lying excited singlet state S1 underwent efficient
intersystem crossing (ISC) to convert into its triplet state with a time constant
of 4 ps. Subsequently, this triplet species dissociated into the benzoyl and
alkyl radicals with a corresponding maximum absorption band at 415 nm. The TR(3)
results in conjunction with results from DFT calculations confirmed that Irgacure
2959 cleaved into the benzoyl and alkyl radicals at a fast rate on the tens of
picosecond time scale.
PMID- 25134067
TI - Circulating PCSK9 levels correlate with the serum LDL cholesterol level in
newborn infants.
AB - BACKGROUND AND AIMS: Protein convertase subtilisin/Kexin type-9 (PCSK9) is a
substantial player in lipoprotein metabolism. This study was designed to
elucidate the role of PCSK9 in the regulation of lipoprotein during the fetal
period. STUDY DESIGN AND SUBJECTS: This study was a cross-sectional study. Eighty
one neonates (45 males, 36 females) who were admitted to the neonatal intensive
care unit were enrolled in the study. The median age in gestational weeks and
weight at birth were 37.1 weeks and 2493 g, respectively. There were no gender
differences, but the proportion of infants who were small-for-gestational age
(SGA) was significantly higher among females than males. The prefed serum PCSK9
level was assayed with ELISA kits. RESULTS: The median PCSK9 concentration in
male newborns was significantly lower than that in females (148.2 ng/ml vs. 171.4
ng/ml, respectively, p<0.001). Circulating serum PCSK9 levels were positively
correlated with total cholesterol (r=0.281, p<0.05) and low-density lipoprotein
cholesterol (LDL-C; r=0.272, p<0.05). However, there were no correlations between
PCSK9 levels and birth weight, gestational age or SGA. Multivariate forward
stepwise linear regression analysis revealed that gestational age and circulating
PCSK9 levels were independent predictors of the serum LDL-C levels in newborn
infants. CONCLUSION: Our first quantitative analysis of neonatal serum PCSK9
levels at birth showed that circulating PCSK9 levels show gender-based
differences and are significantly correlated with LDL-C. These results suggest
that PCSK9 could play an important role in regulating LDL-C levels during the
fetal period.
PMID- 25134068
TI - Composite photothermal platform of polypyrrole-enveloped Fe3O4 nanoparticle self
assembled superstructures.
AB - Photothermal nanoplatforms with small size, low cost, multifunctionality, good
biocompatibility and in particular biodegradability are greatly desired in the
exploration of novel diagnostic and therapeutic methodologies. Despite Fe3O4
nanoparticles (NPs) have been approved as safe clinical agents, the low molar
extinction coefficient and subsequent poor photothermal performance shed the
doubt as effective photothermal materials. In this paper, we demonstrate the
fabrication of polypyrrole (PPy)-enveloped Fe3O4 NP superstructures with a
spherical morphology, which leads to a 300-fold increase in the molar extinction
coefficient. The basic idea is the optimization of Fe3O4 electronic structures.
By controlling the self-assembly of Fe3O4 NPs, the diameters of the
superstructures are tuned from 32 to 64 nm. This significantly enhances the
indirect transition and magnetic coupling of Fe ions, thus increasing the molar
extinction coefficient of Fe3O4 NPs from 3.65 * 10(6) to 1.31 * 10(8) M(-1) cm(
1) at 808 nm. The envelopment of Fe3O4 superstructures with conductive PPy shell
introduces additional electrons in the Fe3O4 oscillation system, and therewith
further enhances the molar extinction coefficient to 1.12 * 10(9) M(-1) cm(-1).
As a result, the photothermal performance is greatly improved. Primary cell
experiments indicate that PPy-enveloped Fe3O4 NP superstructures are low toxic,
and capable to kill Hela cells under near-infrared laser irradiation. Owing to
the low cost, good biocompatibility and biodegradability, the PPy-enveloped Fe3O4
NP superstructures are promising photothermal platform for establishing novel
diagnostic and therapeutic methods.
PMID- 25134066
TI - Fibril elongation by Abeta(17-42): kinetic network analysis of hybrid-resolution
molecular dynamics simulations.
AB - A critical step of beta-amyloid fibril formation is fibril elongation in which
amyloid-beta monomers undergo structural transitions to fibrillar structures upon
their binding to fibril tips. The atomic detail of the structural transitions
remains poorly understood. Computational characterization of the structural
transitions is limited so far to short Abeta segments (5-10 aa) owing to the long
time scale of Abeta fibril elongation. To overcome the computational time scale
limit, we combined a hybrid-resolution model with umbrella sampling and replica
exchange molecular dynamics and performed altogether ~1.3 ms of molecular
dynamics simulations of fibril elongation for Abeta17-42. Kinetic network
analysis of biased simulations resulted in a kinetic model that encompasses all
Abeta segments essential for fibril formation. The model not only reproduces key
properties of fibril elongation measured in experiments, including Abeta binding
affinity, activation enthalpy of Abeta structural transitions and a large time
scale gap (taulock/taudock = 10(3)-10(4)) between Abeta binding and its
structural transitions, but also reveals detailed pathways involving structural
transitions not seen before, namely, fibril formation both in hydrophobic regions
L17-A21 and G37-A42 preceding fibril formation in hydrophilic region E22-A30.
Moreover, the model identifies as important kinetic intermediates strand-loop
strand (SLS) structures of Abeta monomers, long suspected to be related to fibril
elongation. The kinetic model suggests further that fibril elongation arises
faster at the fibril tip with exposed L17-A21, rather than at the other tip,
explaining thereby unidirectional fibril growth observed previously in
experiments.
PMID- 25134069
TI - Active Commuting by Bicycle: Results of an Educational Intervention Study.
AB - OBJECTIVE: The objective of this study was to assess the effectiveness of an
educational intervention on active commuting by bicycle. METHODS: An intervention
study with workers from a metallurgical industry in Santa Catarina state, Brazil
was carried out in 2011. A total of 464 individuals were placed in the
intervention group (IG) and 468 in the control group (CG). The intervention
consisted of strategies based on the transtheoretical model and stages of
behavior change. The intervention group took part in activities for 6 months,
including 23 meetings. The statistical analysis included intergroup comparison
(IG * CG) at baseline and after the intervention. Intragroup analysis was
performed 6 months after the intervention. Student's t-test, chi-square, and
McNemar tests were used to analyze the data. RESULTS: Of the original total, 876
individuals (94%) participated in the study. The proportion of participants that
used bicycles to commute to work (IG) increased significantly from baseline
(45.3%) to the final interventional period (47.5%). No difference was found
between the CG and the IG group after the interventional period. CONCLUSION: We
suggest taking these findings into consideration in further studies to understand
better the role of educational intervention on active commuting by bicycle.
PMID- 25134070
TI - Posthumous gamete retrieval and reproduction: would the deceased spouse consent?
AB - Policy and medical decision-making has been hindered by the absence of reliable
data on attitudes toward having one's own gametes retrieved posthumously and used
to produce a child in the event of an untimely death. The purpose of this study
is to directly and empirically examine whether the presumption against consent is
justified in the case of posthumous gamete retrieval following sudden death.
Respondents (N=2064) were contacted using a random-digit dialing method that gave
every household telephone in the continental United States an equal probability
of being contacted, and were asked: "Suppose you were to experience an early
death and your spouse wanted to have a biological child with you. Would you or
would you not want your spouse to be able to use your sperm/eggs following your
death to have a child with you?" Among reproductive age respondents (18-44
years), 70% of males and 58% of females wanted their spouse to be able to use
their gametes and, for the most part, attitudes were fairly consistent across
demographic characteristics. Religiosity was the best predictor of attitudes-
those who described themselves as more religious were less likely to desire
posthumous gamete retrieval--but the majority (58%) of respondents who were very
religious approved of retrieval. Overall, these data indicate that abandoning the
prevailing presumption against consent in favor of a presumption of consent on
the part of the deceased will result in the deceased's wishes being honored two
and three times more often for females and males, respectively. Three main
arguments against a presumption of consent in this context are discussed:
autonomy of the deceased, conflict of interest, and the decision-making capacity
of a grieving spouse.
PMID- 25134071
TI - Parent-adolescent joint projects involving leisure time and activities during the
transition to high school.
AB - Leisure research to date has generally overlooked planning and organizing of
leisure time and activities between parents and adolescents. This investigation
examined how a sample of Canadian adolescents and their parents jointly
constructed and acted on goals related to adolescents' leisure time during the
move from elementary to high school. Using the Qualitative Action-Project Method,
data were collected over an 8-10 month period from 26 parent-adolescent dyads
located in two urban sites, through video-taped conversations about leisure time,
video recall interviews, and telephone monitoring interviews. Analysis of the
data revealed that the joint projects of the 26 dyads could be grouped into three
clusters: a) governance transfer or attempts to shift, from parent to adolescent,
responsibility over academic demands, organizing leisure time, and safety with
peers, b) balancing extra-curricular activities with family life, academics, and
social activities, and c) relationship adjustment or maintenance.
PMID- 25134072
TI - Thinking about the past, present and future in adolescents growing up in
Children's Homes.
AB - The present study tested the hypothesis that adolescents growing up in Children's
Homes differ from adolescents growing up in a family environment in how they
think about their past, present and future, in the way they make decisions about
future events and rewards, and in their levels of empathy and perspective taking.
The participants were 40 adolescents from Children's Homes in Budapest, Hungary,
and 40 age- and gender-matched controls. Group differences were found in
participants' past and present time perspectives, and girls from Children's Homes
showed reduced consistency in their plans for the future. Additionally, gender
differences emerged in empathy, perspective taking, and in participants' present
and future time perspectives. We discuss the implications of our findings for
interventions to improve the future prospects of adolescents in Children's Homes.
PMID- 25134073
TI - The differential impact of a classroom-based, alcohol harm reduction
intervention, on adolescents with different alcohol use experiences: a multi
level growth modelling analysis.
AB - While evidence has accumulated suggesting that prevention initiatives may have a
limited impact on alcohol use behaviour, reviews suggest that interventions with
most potential for behavioural change are interactive and developmental in
design. The School Health and Alcohol Harm Reduction Project (SHAHRP) is an
example of such an intervention. Researchers are increasingly attempting to
understand the differential effects of programmes in population subgroups. The
present study is a secondary analysis of data from a non-randomised trial of
SHAHRP, a classroom-based alcohol education intervention, involving school
children (aged 13-16 years old) in the United Kingdom. Results showed that there
were significant positive changes in knowledge about and attitudes towards
alcohol in baseline abstainers, supervised drinkers and unsupervised drinkers.
Significant positive behavioural effects in terms of amounts consumed, frequency
of drinking and self-reported alcohol related harms, were observed almost
exclusively among baseline unsupervised drinkers. These behavioural effects
support those previously observed in Australia and suggest that the intervention
is a viable health promotion tool in the UK.
PMID- 25134074
TI - Effects of Active Video Games on Energy Expenditure in Adults: A Systematic
Literature Review.
AB - BACKGROUND: The objective of this study was to estimate the mean difference in
energy expenditure (EE) in healthy adults between playing active video games
(AVGs) compared with traditional video games (TVGs) or rest. METHODS: A
systematic search was conducted on Ovid MEDLINE, Web of Knowledge, and Academic
Search Premier between 1998 and April 2012 for relevant keywords, yielding 15
studies. EE and heart rate (HR) data were extracted, and random effects meta
analysis was performed. RESULTS: EE during AVG play was 1.81 (95% CI, 1.29-2.34;
I2 = 94.2%) kcal/kg/hr higher, or about 108 kcal higher per hour for a 60-kg
person, compared with TVG play. Mean HR was 21 (95% CI, 13.7-28.3; I2 = 93.4%)
beats higher per minute during AVG play compared with TVG play. There was wide
variation in the EE and HR estimates across studies because different games were
evaluated. Overall metabolic equivalent associated with AVG play was 2.62 (95%
CI, 2.25-3.00; I2 = 99.2%), equivalent to a light activity level. Most studies
had low risk of bias due to proper study design and use of indirect calorimetry
to measure EE. CONCLUSION: AVGs may be used to replace sedentary screen time (eg,
television watching or TVG play) with light activity in healthy adults.
PMID- 25134075
TI - Motor imagery is less efficient in adults with probable developmental
coordination disorder: evidence from the hand rotation task.
AB - The present study aimed to provide preliminary insight into the integrity of
motor imagery (MI) in adults with probable developmental coordination disorder
(pDCD). Based on a strong body of evidence indicating that paediatric samples of
DCD often experience difficulties engaging MI, we hypothesised that young adults
with pDCD would demonstrate similar difficulties. The performance of 12 young
adults (19-35 years) with pDCD was compared to 47 age-matched controls on a
traditional mental hand rotation task. Mean inverse efficiency scores were
generated for each participant by dividing each participant's mean RT by their
proportion of correct responses at each of the stimuli presentation conditions.
Preliminary analysis revealed that the performance profiles of individuals with
pDCD and age-matched controls showed evidence of being constrained by the
biomechanical and postural constraints of real movement, suggesting that both
groups engaged in an embodied (MI) strategy to complete the task. Despite
engaging in a MI strategy, however, young adults with pDCD were nonetheless
significantly less efficient when doing so, shown by significant main effects for
group on all group efficiency comparisons. Based on the assumption that MI
provides insight into the internal 'neural' action representation that precedes
action, we argue that the less efficient MI performance demonstrated by young
adults with pDCD may indicate inefficiencies engaging or implementing internal
action representations. Implications and directions for future research are
discussed.
PMID- 25134076
TI - Differences between late preterm and full-term infants: comparing effects of a
short bout of practice on early reaching behavior.
AB - This study compared the effects of a short bout of practice on reaching behavior
between late preterm and full-term infants at the onset of goal-directed
reaching. Twelve late preterm infants and twelve full-term infants received
reaching practice based on a serial schedule. Late preterm and full-term infants
were assessed in 3.3+/-1.4 and 2.6+/-1.0 days after the onset of goal-directed
reaching in two measures in a single day: immediately before practice (pre-test)
and immediately after practice (post-test). During the assessments, the infants
were placed in a baby chair and a rubber toy was presented at their midline
within reaching distance for 2 min. Between assessments, the infants received
practice of toy-oriented reaching in 3 activities repeated for approximately 4
min. The activities were elicited in a pre-established serial sequence and were
applied by a physical therapist. During the pre-test, late preterm infants
presented lower range of proximal adjustments, greater proportion of reaches with
semi-open hand, and greater proportion of reaches without grasping than the full
term infants. During the post-test, late preterm infants presented greater motor
variability of proximal adjustments, but explored and selected distal control and
grasping outcomes less compared to the full-term group. Differences in reaching
and gross motor behavior between late preterm and full-term infants can be found
at the age of reaching onset. Practice provided new opportunities for late
preterm infants to improve perception-action coupling to reach; however, relative
to full-terms, they seemed less advanced in benefiting from the experience for
more refined manual tasks.
PMID- 25134079
TI - Image search reranking with query-dependent click-based relevance feedback.
AB - Our goal is to boost text-based image search results via image reranking. There
are diverse modalities (features) of images that we can leverage for reranking,
however, the effects of different modalities are query-dependent. The primary
challenge we face is how to fuse multiple modalities adaptively for different
queries, which has often been overlooked in previous reranking research.
Moreover, multimodality fusion without an understanding of the query is risky,
and may lead to incorrect judgment in reranking. Therefore, to obtain the best
fusion weights for the query, in this paper, we leverage click-through data,
which can be viewed as an "implicit" user feedback and an effective means of
understanding the query. A novel reranking algorithm, called click-based
relevance feedback, is proposed. This algorithm emphasizes the successful use of
click-through data for identifying user search intention, while leveraging
multiple kernel learning algorithm to adaptively learn the query-dependent fusion
weights for multiple modalities. We conduct experiments on a real-world data set
collected from a commercial search engine with click-through data. Encouraging
experimental results demonstrate that our proposed reranking approach can
significantly improve the NDCG@10 of the initial search results by 11.62%, and
can outperform several existing approaches for most kinds of queries, such as
tail, middle, and top queries.
PMID- 25134078
TI - Accelerated phase-cycled SSFP imaging with compressed sensing.
AB - Balanced steady-state free precession (SSFP) imaging suffers from irrecoverable
signal losses, known as banding artifacts, in regions of large B0 field
inhomogeneity. A common solution is to acquire multiple phase-cycled images each
with a different frequency sensitivity, such that the location of banding
artifacts are shifted in space. These images are then combined to alleviate
signal loss across the entire field-of-view. Although high levels of artifact
suppression are viable using a large number of images, this is a time costly
process that limits clinical utility. Here, we propose to accelerate individual
acquisitions such that the overall scan time is equal to that of a single SSFP
acquisition. Aliasing artifacts and noise are minimized by using a variable
density random sampling pattern in k-space, and by generating disjoint sampling
patterns for separate acquisitions. A sparsity-enforcing method is then used for
image reconstruction. Demonstrations on realistic brain phantom images, and in
vivo brain and knee images are provided. In all cases, the proposed technique
enables robust SSFP imaging in the presence of field inhomogeneities without
prolonging scan times.
PMID- 25134080
TI - Advanced screen content coding using color table and index map.
AB - This paper presents an advanced screen content coding solution using color table
and index map (cTIM) method. This cTIM scheme is implemented in the range
extensions of high-efficiency video coding (HEVC-RExt) as an additional tool of
intracoding to complement conventional spatial angular prediction to better
exploit the screen content redundancy. For each coding unit, a number of major
colors will be selected to form the color table, then the original pixel block is
translated to the corresponding index map. A 1D or hybrid 1D/2D string match
scheme is introduced to derive matched pairs of index map for better compression.
Leveraging the color distribution similarity between neighboring image blocks,
color table merge is developed to carry it implicitly. For those blocks that
color table has to be signaled explicitly, intertable color sharing and
intratable color differential predictive coding are applied to reduce the
signaling overhead. Extensive experiments have been performed and they have
demonstrated the significant coding efficiency improvement over conventional HEVC
RExt, resulting in 26%, 18%, and 15% bit rate reduction at lossless case and 23%,
19%, and 13% Bjontegaard Delta-rate improvement at lossy scenario of typical
screen content with text and graphics, for respective all intra, random access,
and low-delay using B picture encoder settings. Detailed performance study and
complexity analysis (as well as the comparison with other algorithms) have been
included as well to evidence the efficiency of proposed algorithm.
PMID- 25134081
TI - Face super-resolution via multilayer locality-constrained iterative neighbor
embedding and intermediate dictionary learning.
AB - Based on the assumption that low-resolution (LR) and high-resolution (HR)
manifolds are locally isometric, the neighbor embedding super-resolution
algorithms try to preserve the geometry (reconstruction weights) of the LR space
for the reconstructed HR space, but neglect the geometry of the original HR
space. Due to the degradation process of the LR image (e.g., noisy, blurred, and
down-sampled), the neighborhood relationship of the LR space cannot reflect the
truth. To this end, this paper proposes a coarse-to-fine face super-resolution
approach via a multilayer locality-constrained iterative neighbor embedding
technique, which intends to represent the input LR patch while preserving the
geometry of original HR space. In particular, we iteratively update the LR patch
representation and the estimated HR patch, and meanwhile an intermediate
dictionary learning scheme is employed to bridge the LR manifold and original HR
manifold. The proposed method can faithfully capture the intrinsic image
degradation shift and enhance the consistency between the reconstructed HR
manifold and the original HR manifold. Experiments with application to face super
resolution on the CAS-PEAL-R1 database and real-world images demonstrate the
power of the proposed algorithm.
PMID- 25134082
TI - Practical signal-dependent noise parameter estimation from a single noisy image.
AB - The additive white Gaussian noise is widely assumed in many image processing
algorithms. However, in the real world, the noise from actual cameras is better
modeled as signal-dependent noise (SDN). In this paper, we focus on the SDN model
and propose an algorithm to automatically estimate its parameters from a single
noisy image. The proposed algorithm identifies the noise level function of signal
dependent noise assuming the generalized signal-dependent noise model and is also
applicable to the Poisson-Gaussian noise model. The accuracy is achieved by
improved estimation of local mean and local noise variance from the selected low
rank patches. We evaluate the proposed algorithm with both synthetic and real
noisy images. Experiments demonstrate that the proposed estimation algorithm
outperforms the state-of-the-art methods.
PMID- 25134083
TI - Automatic segmentation of mitochondria in EM data using pairwise affinity
factorization and graph-based contour searching.
AB - In this paper, we investigate the segmentation of closed contours in subcellular
data using a framework that primarily combines the pairwise affinity grouping
principles with a graph partitioning contour searching approach. One salient
problem that precluded the application of these methods to large scale
segmentation problems is the onerous computational complexity required to
generate comprehensive representations that include all pairwise relationships
between all pixels in the input data. To compensate for this problem, a practical
solution is to reduce the complexity of the input data by applying an over
segmentation technique prior to the application of the computationally demanding
strands of the segmentation process. This approach opens the opportunity to build
specific shape and intensity models that can be successfully employed to extract
the salient structures in the input image which are further processed to identify
the cycles in an undirected graph. The proposed framework has been applied to the
segmentation of mitochondria membranes in electron microscopy data which are
characterized by low contrast and low signal-to-noise ratio. The algorithm has
been quantitatively evaluated using two datasets where the segmentation results
have been compared with the corresponding manual annotations. The performance of
the proposed algorithm has been measured using standard metrics, such as
precision and recall, and the experimental results indicate a high level of
segmentation accuracy.
PMID- 25134084
TI - An assistive control approach for a lower-limb exoskeleton to facilitate recovery
of walking following stroke.
AB - This paper presents a control approach for a lower-limb exoskeleton intended to
facilitate recovery of walking in individuals with lower-extremity hemiparesis
after stroke. The authors hypothesize that such recovery is facilitated by
allowing the patient rather than the exoskeleton to provide movement
coordination. As such, an assistive controller that provides walking assistance
without dictating the spatiotemporal nature of joint movement is described here.
Following a description of the control laws and finite state structure of the
controller, the authors present the results of an experimental implementation and
preliminary validation of the control approach, in which the control architecture
was implemented on a lower limb exoskeleton, and the exoskeleton implemented in
an experimental protocol on three subjects with hemiparesis following stroke. In
a series of sessions in which each patient used the exoskeleton, all patients
showed substantial single-session improvements in all measured gait outcomes,
presumably as a result of using the assistive controller and exoskeleton.
PMID- 25134085
TI - FORCe: Fully Online and Automated Artifact Removal for Brain-Computer
Interfacing.
AB - A fully automated and online artifact removal method for the electroencephalogram
(EEG) is developed for use in brain-computer interfacing (BCI). The method
(FORCe) is based upon a novel combination of wavelet decomposition, independent
component analysis, and thresholding. FORCe is able to operate on a small channel
set during online EEG acquisition and does not require additional signals (e.g.,
electrooculogram signals). Evaluation of FORCe is performed offline on EEG
recorded from 13 BCI particpants with cerebral palsy (CP) and online with three
healthy participants. The method outperforms the state-of the-art automated
artifact removal methods Lagged Auto-Mutual Information Clustering (LAMIC) and
Fully Automated Statistical Thresholding for EEG artifact Rejection (FASTER), and
is able to remove a wide range of artifact types including blink, electromyogram
(EMG), and electrooculogram (EOG) artifacts.
PMID- 25134086
TI - Guest editorial. Special section on molecular communication.
PMID- 25134087
TI - Real-time emulator for reproducing graded potentials in vertebrate retina.
AB - In most parts of the retina, neuronal circuits process visual signals represented
by slowly changing membrane potentials, or so-called graded potentials. A
feasible approach to speculate about the functional roles of retinal neuronal
circuits is to reproduce the graded potentials of retinal neurons in response to
natural scenes. In this study, we developed a simulation platform for reproducing
graded potentials with the following features: real-time reproduction of retinal
neural activities in response to natural scenes, a configurable model structure,
and compact hardware. The spatio-temporal properties of neurons were emulated
efficiently by a mixed analog-digital architecture that consisted of analog
resistive networks and a field-programmable gate array. The neural activities on
sustained and transient pathways were emulated from 128 * 128 inputs at 200
frames per second.
PMID- 25134088
TI - 30 pJ/b, 67 Mbps, Centimeter-to-Meter Range Data Telemetry With an IR-UWB
Wireless Link.
AB - This paper reports an energy-efficient, impulse radio ultra wideband (IR-UWB)
wireless link operating in 3-5 GHz for data telemetry over centimeter-to-meter
range distances at rates extended to tens of Mbps. The link comprises an all
digital, integrated transmitter (TX) fabricated in 90 nm 1P/9M CMOS that
incorporates a waveform-synthesis pulse generator and a timing generator for on
off-keying (OOK) pulse modulation and phase scrambling. The link also
incorporates an energy-detection receiver (RX) realized with commercial off-the
shelf (COTS) components that performs radio-frequency (RF) filtering,
amplification, logarithmic power detection for data demodulation and automatic
level control for robust operation in the presence of distance variations.
Employing a miniaturized, UWB, chip antenna for the TX and RX, wireless
transmission of pseudo-random binary sequence (PRBS) data at rates up to 50 Mbps
over 10 cm-1 m is shown. Further, employing a high-gain horn antenna for the RX,
wireless transmission of PRBS data at rates up to 67 Mbps over 50 cm-4 m is shown
with a TX energy consumption of 30 pJ/b (i.e., power consumption of 2 mW) from
1.2 V. The measured bit error rate (BER) in both cases is < 10(-7) . Results from
wireless recording of the background current of a carbon-fiber microelectrode
(CFM) in one fast-scan cyclic voltammetry (FSCV) scan using the IR-UWB link are
also included, exhibiting excellent match with those obtained from a conventional
frequency-shift-keyed (FSK) link at ~433 MHz.
PMID- 25134089
TI - An Implantable Versatile Electrode-Driving ASIC for Chronic Epidural Stimulation
in Rats.
AB - This paper presents the design and testing of an electrode driving application
specific integrated circuit (ASIC) intended for epidural spinal cord electrical
stimulation in rats. The ASIC can deliver up to 1 mA fully programmable
monophasic or biphasic stimulus current pulses, to 13 electrodes selected in any
possible configuration. It also supports interleaved stimulation. Communication
is achieved via only 3 wires. The current source and the control of the
stimulation timing were kept off-chip to reduce the heat dissipation close to the
spinal cord. The ASIC was designed in a 0.18- MUm high voltage CMOS process. Its
output voltage compliance can be up to 25 V. It features a small core area
(<;0.36 mm(2)) and consumes a maximum of 114 MUW during a full stimulation cycle.
The layout of the ASIC was developed to be suitable for integration on the
epidural electrode array, and two different versions were fabricated and
electrically tested. Results from both versions were almost indistinguishable.
The performance of the system was verified for different loads and stimulation
parameters. Its suitability to drive a passive epidural 12-electrode array in
saline has also been demonstrated.
PMID- 25134090
TI - A New Fully Differential CMOS Capacitance to Digital Converter for Lab-on-Chip
Applications.
AB - In this paper, we present a new differential CMOS capacitive sensor for Lab-on
Chip applications. The proposed integrated sensor features a DC-input SigmaDelta
capacitance to digital converter (CDC) and two reference and sensing
microelectrodes integrated on the top most metal layer in 0.35 MUm CMOS process.
Herein, we describe a readout circuitry with a programmable clocking strategy
using a Charge Based Capacitance Measurement technique. The simulation and
experimental results demonstrate a high capacitive dynamic range of 100 fF-110
fF, the sensitivity of 350 mV/fF and the minimum detectable capacitance variation
of as low as 10 aF. We also demonstrate and discuss the use of this device for
environmental applications through various chemical solvents.
PMID- 25134091
TI - FREL: A Stable Feature Selection Algorithm.
AB - Two factors characterize a good feature selection algorithm: its accuracy and
stability. This paper aims at introducing a new approach to stable feature
selection algorithms. The innovation of this paper centers on a class of stable
feature selection algorithms called feature weighting as regularized energy-based
learning (FREL). Stability properties of FREL using L1 or L2 regularization are
investigated. In addition, as a commonly adopted implementation strategy for
enhanced stability, an ensemble FREL is proposed. A stability bound for the
ensemble FREL is also presented. Our experiments using open source real
microarray data, which are challenging high dimensionality small sample size
problems demonstrate that our proposed ensemble FREL is not only stable but also
achieves better or comparable accuracy than some other popular stable feature
weighting methods.
PMID- 25134092
TI - Nonlinear Topological Component Analysis: Application to Age-Invariant Face
Recognition.
AB - We introduce a novel formalism that performs dimensionality reduction and
captures topological features (such as the shape of the observed data) to conduct
pattern classification. This mission is achieved by: 1) reducing the dimension of
the observed variables through a kernelized radial basis function technique and
expressing the latent variables probability distribution in terms of the observed
variables; 2) disclosing the data manifold as a 3-D polyhedron via the alpha
shape constructor and extracting topological features; and 3) classifying a data
set using a mixture of multinomial distributions. We have applied our methodology
to the problem of age-invariant face recognition. Experimental results obtained
demonstrate the efficiency of the proposed methodology named nonlinear
topological component analysis when compared with some state-of-the-art
approaches.
PMID- 25134093
TI - On Equivalence of FIS and ELM for Interpretable Rule-Based Knowledge
Representation.
AB - This paper presents a fuzzy extreme learning machine (F-ELM) that embeds fuzzy
membership functions and rules into the hidden layer of extreme learning machine
(ELM). Similar to the concept of ELM that employed the random initialization
technique, three parameters of F-ELM are randomly assigned. They are the standard
deviation of the membership functions, matrix-C (rule-combination matrix), and
matrix-D [don't care (DC) matrix]. Fuzzy if-then rules are formulated by the rule
combination Matrix of F-ELM, and a DC approach is adopted to minimize the number
of input attributes in the rules. Furthermore, F-ELM utilizes the output weights
of the ELM to form the target class and confidence factor for each of the rules.
This is to indicate that the corresponding consequent parameters are determined
analytically. The operations of F-ELM are equivalent to a fuzzy inference system.
Several benchmark data sets and a real world fault detection and diagnosis
problem have been used to empirically evaluate the efficacy of the proposed F-ELM
in handling pattern classification tasks. The results show that the accuracy
rates of F-ELM are comparable (if not superior) to ELM with distinctive ability
of providing explicit knowledge in the form of interpretable rule base.
PMID- 25134094
TI - Incremental Support Vector Learning for Ordinal Regression.
AB - Support vector ordinal regression (SVOR) is a popular method to tackle ordinal
regression problems. However, until now there were no effective algorithms
proposed to address incremental SVOR learning due to the complicated formulations
of SVOR. Recently, an interesting accurate on-line algorithm was proposed for
training nu -support vector classification (nu-SVC), which can handle a quadratic
formulation with a pair of equality constraints. In this paper, we first present
a modified SVOR formulation based on a sum-of-margins strategy. The formulation
has multiple constraints, and each constraint includes a mixture of an equality
and an inequality. Then, we extend the accurate on-line nu-SVC algorithm to the
modified formulation, and propose an effective incremental SVOR algorithm. The
algorithm can handle a quadratic formulation with multiple constraints, where
each constraint is constituted of an equality and an inequality. More
importantly, it tackles the conflicts between the equality and inequality
constraints. We also provide the finite convergence analysis for the algorithm.
Numerical experiments on the several benchmark and real-world data sets show that
the incremental algorithm can converge to the optimal solution in a finite number
of steps, and is faster than the existing batch and incremental SVOR algorithms.
Meanwhile, the modified formulation has better accuracy than the existing
incremental SVOR algorithm, and is as accurate as the sum-of-margins based
formulation of Shashua and Levin.
PMID- 25134095
TI - Adaptive NN Control of a Class of Nonlinear Systems With Asymmetric Saturation
Actuators.
AB - In this note, adaptive neural network (NN) control is investigated for a class of
uncertain nonlinear systems with asymmetric saturation actuators and external
disturbances. To handle the effect of nonsmooth asymmetric saturation
nonlinearity, a Gaussian error function-based continuous differentiable
asymmetric saturation model is employed such that the backstepping technique can
be used in the control design. The explosion of complexity in traditional
backstepping design is avoided using dynamic surface control. Using radial basis
function NN, adaptive control is developed to guarantee that all the signals in
the closed-loop system are semiglobally uniformly ultimately bounded, and the
tracking error converges to a small neighborhood of origin by appropriately
choosing design constants. The effectiveness of the proposed control is
demonstrated in the simulation study.
PMID- 25134096
TI - Clause states based configuration checking in local search for satisfiability.
AB - Two-mode stochastic local search (SLS) and focused random walk (FRW) are the two
most influential paradigms of SLS algorithms for the propositional satisfiability
(SAT) problem. Recently, an interesting idea called configuration checking (CC)
was proposed to handle the cycling problem in SLS. The CC idea has been
successfully used to improve SLS algorithms for SAT, resulting in state-of-the
art solvers. Previous CC strategies for SAT are based on neighboring variables,
and prove successful in two-mode SLS algorithms. However, this kind of
neighboring variables based CC strategy is not suitable for improving FRW
algorithms. In this paper, we propose a new CC strategy which is based on clause
states. We apply this clause states based CC (CSCC) strategy to both two-mode SLS
and FRW paradigms. Our experiments show that the CSCC strategy is effective on
both paradigms. Furthermore, our developed FRW algorithms based on CSCC achieve
state-of-the-art performance on a broad range of random SAT benchmarks.
PMID- 25134097
TI - Rating knowledge sharing in cross-domain collaborative filtering.
AB - Cross-domain collaborative filtering (CF) aims to share common rating knowledge
across multiple related CF domains to boost the CF performance. In this paper, we
view CF domains as a 2-D site-time coordinate system, on which multiple related
domains, such as similar recommender sites or successive time-slices, can share
group-level rating patterns. We propose a unified framework for cross-domain CF
over the site-time coordinate system by sharing group-level rating patterns and
imposing user/item dependence across domains. A generative model, say ratings
over site-time (ROST), which can generate and predict ratings for multiple
related CF domains, is developed as the basic model for the framework. We further
introduce cross-domain user/item dependence into ROST and extend it to two real
world cross-domain CF scenarios: 1) ROST (sites) for alleviating rating sparsity
in the target domain, where multiple similar sites are viewed as related CF
domains and some items in the target domain depend on their correspondences in
the related ones; and 2) ROST (time) for modeling user-interest drift over time,
where a series of time-slices are viewed as related CF domains and a user at
current time-slice depends on herself in the previous time-slice. All these ROST
models are instances of the proposed unified framework. The experimental results
show that ROST (sites) can effectively alleviate the sparsity problem to improve
rating prediction performance and ROST (time) can clearly track and visualize
user-interest drift over time.
PMID- 25134098
TI - Operating to remove recurrent colorectal cancer: have we got it right?
PMID- 25134099
TI - Anteroposterior left vertebral angiogram.
PMID- 25134102
TI - Ecological studies: advantages and disadvantages.
PMID- 25134100
TI - Long term maintenance of weight loss with non-surgical interventions in obese
adults: systematic review and meta-analyses of randomised controlled trials.
AB - OBJECTIVE: To systematically review and describe currently available approaches
to supporting maintenance of weight loss in obese adults and to assess the
evidence for the effectiveness of these interventions. DESIGN: Systematic review
with meta-analysis. DATA SOURCES: Medline, PsycINFO, Embase, and the Cochrane
Central Register of Controlled Trials. STUDY SELECTION: Studies were identified
through to January 2014. Randomised trials of interventions to maintain weight
loss provided to initially obese adults (aged >= 18) after weight loss of >= 5%
body weight with long term (>= 12 months) follow-up of weight change (main
outcome) were included. STUDY APPRAISAL AND SYNTHESIS: Potential studies were
screened independently and in duplicate; study characteristics and outcomes were
extracted. Meta-analyses were conducted to estimate the effects of interventions
on weight loss maintenance with the inverse variance method and a random effects
model. Results are presented as mean differences in weight change, with 95%
confidence intervals. RESULTS: 45 trials involving 7788 individuals were
included. Behavioural interventions focusing on both food intake and physical
activity resulted in an average difference of -1.56 kg (95% confidence interval
2.27 to -0.86 kg; 25 comparisons, 2949 participants) in weight regain compared
with controls at 12 months. Orlistat combined with behavioural interventions
resulted in a -1.80 kg (-2.54 to -1.06; eight comparisons, 1738 participants)
difference compared with placebo at 12 months. All orlistat studies reported
higher frequencies of adverse gastrointestinal events in the experimental
compared with placebo control groups. A dose-response relation for orlistat
treatment was found, with 120 mg doses three times a day leading to greater
weight loss maintenance (-2.34 kg, -3.03 to -1.65) compared with 60 mg and 30 mg
three times a day (-0.70 kg, 95% confidence interval -1.92 to 0.52), P=0.02.
CONCLUSIONS: Behavioural interventions that deal with both diet and physical
activity show small but significant benefits on weight loss maintenance.
PMID- 25134103
TI - Why schools should promote students' health and wellbeing.
PMID- 25134101
TI - Quantification of risk factors for herpes zoster: population based case-control
study.
AB - OBJECTIVES: To quantify the effects of possible risk factors for herpes zoster at
different ages. DESIGN: Case-control study. SETTING: UK Clinical Practice
Research Datalink primary care data. PARTICIPANTS: 144 959 adults diagnosed with
zoster between 2000 and 2011; 549,336 age, sex, and practice matched controls.
MAIN OUTCOME MEASURES: Conditional logistic regression was used to generate
adjusted odds ratios to estimate the strength of association of each potential
risk factor with zoster and assess effect modification by age. RESULTS: The
median age of the cases and controls was 62 years. Factors associated with
increased risk of zoster included rheumatoid arthritis (3111 (2.1%) v 8029
(1.5%); adjusted odds ratio 1.46, 99% confidence interval 1.38 to 1.55),
inflammatory bowel disease (1851 (1.3%) v 5118 (0.9%); 1.36, 1.26 to 1.46),
chronic obstructive pulmonary disease (6815 (4.7%) v 20 201 (3.7%); 1.32, 1.27 to
1.37), asthma (10 243 (7.1%) v 31 865 (5.8%); 1.21, 1.17 to 1.25), chronic kidney
disease (8724 (6.0%) v 29 437 (5.4%); 1.14, 1.09 to 1.18), and depression (6830
(4.7%) v 22 052 (4.0%); 1.15, 1.10 to 1.20). Type 1, but not type 2, diabetes
showed some association with zoster (adjusted odds ratio 1.27, 1.07 to 1.50). The
relative effects of many assessed risk factors were larger in younger patients.
Patients with severely immunosuppressive conditions were at greatest risk of
zoster-for example, patients with lymphoma (adjusted odds ratio 3.90, 3.21 to
4.74) and myeloma (2.16, 1.84 to 2.53), who are not eligible for zoster
vaccination. CONCLUSIONS: A range of conditions were associated with increased
risk of zoster. In general, the increased risk was proportionally greater in
younger age groups. Current vaccines are contraindicated in people at the
greatest risk of zoster, highlighting the need for alternative risk reduction
strategies in these groups.
PMID- 25134104
TI - A student with macrocytic anaemia.
PMID- 25134105
TI - AMA data operation makes millions, even monitors non-members.
PMID- 25134106
TI - The "Saatchi bill" is mistargeted and will put vulnerable patients at risk.
PMID- 25134107
TI - The "Saatchi bill" will cause serious problems for the medical profession.
PMID- 25134108
TI - The Saatchi gamble that law will drive creativity in medicine.
PMID- 25134109
TI - "Saatchi bill": legal hurdles and clinical irrelevance.
PMID- 25134110
TI - Maintenance treatment for adults with chronic asthma.
PMID- 25134111
TI - No medical innovation without accessible documentation.
PMID- 25134112
TI - Author's reply to Poole, Conway, Bewley, Sundar, and Chalmers and Firkins.
PMID- 25134113
TI - The need for initial specialist assessment in suspected dementia.
PMID- 25134114
TI - The difficulty and dangers of diagnosing dementia.
PMID- 25134115
TI - Power imbalance prevents shared decision making.
PMID- 25134116
TI - Financing for health in India.
PMID- 25134118
TI - What is a crossover trial?
PMID- 25134119
TI - Achieving quality of care in dementia by appropriate and timely diagnosis.
PMID- 25134117
TI - Effects of nutritional supplementation for HIV patients starting antiretroviral
treatment: randomised controlled trial in Ethiopia.
AB - OBJECTIVES: To determine the effects of lipid based nutritional supplements with
either whey or soy protein in patients with HIV during the first three months of
antiretroviral treatment (ART) and to explore effects of timing by comparing
supplementation at the start of ART and after three months delay. DESIGN:
Randomised controlled trial. SETTING: Three public ART facilities in Jimma,
Oromia region, Ethiopia. PARTICIPANTS: Adults with HIV eligible for ART with body
mass index (BMI) >16. INTERVENTION: Daily supplementation with 200 g (4600 kJ) of
supplement containing whey or soy during either the first three or the subsequent
three months of ART. OUTCOME MEASURES: Primary: lean body mass assessed with
deuterium dilution, grip strength measured with dynamometers, and physical
activity measured with accelerometer and heart rate monitors. Secondary: viral
load and CD4 counts. Auxiliary: weight and CD3 and CD8 counts. RESULTS: Of 318
patients enrolled, 210 (66%) were women, mean age was 33 (SD 9), and mean BMI was
19.5 (SD 2.4). At three months, participants receiving the supplements containing
whey or soy had increased their lean body mass by 0.85 kg (95% confidence
interval 0.16 kg to 1.53 kg) and 0.97 kg (0.29 kg to 1.64 kg), respectively, more
than controls. This was accompanied by an increased gain of grip strength of 0.68
kg (-0.11 kg to 1.46 kg) for the whey supplement group and 0.93 kg (0.16 kg to
1.70 kg) for the soy supplement group. There were no effects on physical
activity. Total weight gain increased by 2.05 kg (1.12 kg to 2.99 kg) and 2.06 kg
(1.14 kg to 2.97 kg) for the whey and soy groups, respectively. In addition, in
the whey supplement group overall CD3 counts improved by 150 cells/uL (24 to 275
cells/uL), of which 112 cells/uL (15 to 209 cells/uL) were CD8 and 25 cells/uL (
2 to 53 cells/uL) were CD4. Effects of the soy containing supplement on immune
recovery were not significant. The effects of the two supplements, however, were
not significantly different in direct comparison. Exploratory analysis showed
that relatively more lean body mass was gained by patients with undetectable
viral load at three months. Patients receiving delayed supplementation had higher
weight gain but lower gains in functional outcomes. CONCLUSIONS: Lipid based
nutritional supplements improved gain of weight, lean body mass, and grip
strength in patients with HIV starting ART. Supplements containing whey were
associated with improved immune recovery. Trial registration Controlled
trials.com ISRCTN32453477.
PMID- 25134121
TI - Alistair Burns: slippery when wet.
PMID- 25134122
TI - Author's reply to Sleath, Coebergh, and Burns and colleagues.
PMID- 25134123
TI - Nutritional survey data are inaccurate.
PMID- 25134124
TI - Lack of evidence that saturated fat causes cardiovascular disease.
PMID- 25134125
TI - Authors' reply to Winkler and Ravnskov.
PMID- 25134126
TI - Collecting data on female genital mutilation.
PMID- 25134128
TI - Obesity and lower teenage pregnancy rates.
PMID- 25134127
TI - Reception of the "Saatchi bill".
PMID- 25134129
TI - The world's deadliest animal.
PMID- 25134130
TI - Care of dying review shows shortcomings in palliative care.
PMID- 25134131
TI - MPs and peers call for greater patient power.
PMID- 25134133
TI - Girl of 13 has the capacity to decide to have an abortion, High Court rules.
PMID- 25134132
TI - Newborn babies will be tested for four more disorders, committee decides.
PMID- 25134134
TI - Two thirds of British public think spending on NHS should increase.
PMID- 25134135
TI - General practice needs investment to provide enhanced services, says BMA.
PMID- 25134136
TI - Guidelines underestimate US cervical cancer rates and older women's risk, study
finds.
PMID- 25134137
TI - Labour would divert L100 m from NHS reorganisation into primary care.
PMID- 25134139
TI - Resources for emergency laparotomy vary widely across England and Wales.
PMID- 25134140
TI - Researchers commit to greater openness on research involving animals in the UK.
PMID- 25134141
TI - Adverse effects of statins.
PMID- 25134142
TI - I certified deaths after judicial executions--and I believe capital punishment
should be abolished.
PMID- 25134143
TI - NHS Choose and Book appointment system will be replaced.
PMID- 25134145
TI - Drug development is at risk from proposed takeover of AstraZeneca, MPs are told.
PMID- 25134149
TI - Medicare spends billions on "low value" services, US study finds.
PMID- 25134147
TI - Hospital ownership of doctors' practices is linked to higher prices and spending,
US study finds.
PMID- 25134150
TI - Alcohol consumption kills 3.3 million people a year, WHO calculates.
PMID- 25134151
TI - New guidance urges NHS commissioners to buy ethically.
PMID- 25134152
TI - Merger with AstraZeneca will create a scientific "powerhouse," says Pfizer.
PMID- 25134153
TI - US citizens are living longer and consuming more prescription drugs than ever,
finds report.
PMID- 25134154
TI - Boehringer Ingelheim increases access to clinical trial data.
PMID- 25134155
TI - NICE advises certain groups to take daily vitamin D supplement.
PMID- 25134163
TI - Transverse ultrasound scan of the upper abdomen.
PMID- 25134165
TI - Art in the asylum.
PMID- 25134166
TI - James Bell Pettigrew (1832-1908).
PMID- 25134167
TI - End-of-life communications.
PMID- 25134168
TI - Management of hyperkalaemia.
PMID- 25134169
TI - Authors' reply.
PMID- 25134171
TI - Radiotherapy should be omitted in most patients.
PMID- 25134172
TI - Patients at high risk for recurrence need radiotherapy.
PMID- 25134173
TI - Investigation of foot-and-mouth disease outbreaks in the Mbala and Kazungula
districts of Zambia.
AB - Foot-and-mouth disease (FMD) is an acute, highly contagious viral infection of
domestic and wild cloven-hoofed animals. It is known to be endemic in Zambia,
with periodic outbreaks occurring in different geographical areas of the country.
This study was conducted to investigate the presence of FMD virus (FMDV) in
reported FMD-suspected cases in cattle from the Kazungula and Mbala districts of
Zambia. Sixty epithelial tissues or oesophageal-pharyngeal (OP) scrapings
(probang samples) were collected from Mbala (n = 51) and Kazungula (n = 9) and
examined for FMDV. The FMDV viral RNA and serotypes were examined by realtime
reverse transcription polymerase chain reaction (qRT-PCR) and antigen Enzyme-
linked immunosorbent assay (ELISA), respectively. Twenty-two samples (36.7%) were
positive for the FMDV genome by qRT-PCR with Cycle threshold (Ct) values ranging
from 13 to 31. The FMDV-positive samples from epithelial tissues showed
relatively higher Ct values compared to those obtained from OP scrapings,
irrespective of geographical location. Forty percent (40%; n = 4) of epithelial
tissues from Mbala were serotyped into SAT 2 serotype by antigen ELISA. Kazungula
samples were serotyped into SAT 1. These findings indicated that Mbala and
Kazungula districts had FMD outbreaks in 2012 that were ascribed to at least FMDV
serotype SAT 2 and SAT 1 field strains. Furthermore, regular interaction between
buffalos from the Mosi-o Tunya Park and domestic animals from surrounding areas
could contribute to the occurrence of regular FMD outbreaks in Kazungula, whilst
the uncontrolled animal movements across borders between Mbala and Nsumbawanga
could be responsible for disease outbreaks in Mbala. In-depth molecular
biological studies, including sequencing and phylogeny of the viruses, should be
conducted to elucidate the complex epidemiology of FMD in Zambia, thereby
providing valuable information needed for the rational control strategy of FMD in
Zambia and neighbouring countries.
PMID- 25134174
TI - Preliminary investigation on presence of peste des petits ruminants in Dakawa,
Mvomero district, Morogoro region, Tanzania.
AB - Peste des petits ruminants (PPR) is an acute viral disease of small ruminants
characterised by the sudden onset of depression, fever, oculonasal discharges,
sores in the mouth, foul-smelling diarrhoea and death. For many years, in Africa,
the disease was mainly confined to West and Central Africa but it has now spread
southwards to previously PPR-free countries including Tanzania, Democratic
Republic of Congo and Angola. The disease was first reported in Tanzania in 2008
when it was confined to the Northern Zone districts bordering Kenya. Presence of
the disease has also been confirmed in southern Tanzania especially Mtwara
region. Recently, a suspected outbreak of PPR in Dakawa area, Mvomero district,
Morogoro region was reported. Clinical samples (lungs, intestines, lymph nodes,
whole blood and sera) from suspected goats (n = 8) and sheep (n = 1) were
submitted to Sokoine University of Agriculture for analysis. Molecular diagnosis
by amplification of the nucleoprotein gene and the fusion gene of PPR virus
(PPRV) using PPRV specific primers was done. Five goats and the sheep were
positive for PPRV after performing RT-PCR. To our knowledge, this is the first
report confirming the presence of PPR in the Mvomero district of the Morogoro
region, Tanzania. Hence, more efforts should be put in place to prevent the
spread of PPR in Tanzania.
PMID- 25134175
TI - More treatment is not always better.
PMID- 25134176
TI - Transplantation remains significantly underused.
PMID- 25134177
TI - The balance is shifting away from screening.
PMID- 25134178
TI - The argument for breast cancer screening.
PMID- 25134179
TI - Gene dreams.
AB - I remember sitting in one of my genetics lectures in the early days of university
and being in awe of the complexity of the human being but also at science's
ability to probe it. We were in the thick of The Human Genome Project's
culmination and all that it promised for the future of medicine. My mind wandered
from the nitty-gritty of base pairs to imagine a time when one's personalised
blueprint would be an essential tool in the doctor's armament, as commonplace and
essential as a full blood examination or electrocardiogram.
PMID- 25134180
TI - Overdiagnosis: a necessary part of the learning curve towards excellence.
PMID- 25134181
TI - What is the optimal dose of vitamin D?
PMID- 25134182
TI - Reply: To PMID 25134181.
PMID- 25134183
TI - [Scientific research activities in the Czech surgery].
PMID- 25134184
TI - Look in the mirror.
PMID- 25134185
TI - It's just a business decision.
PMID- 25134186
TI - The relationship between gamma-glutamyl transferase levels and chronic kidney
disease among Appalachian adults.
AB - BACKGROUND: Serum gamma-glutamyl transferase (GGT), a marker of oxidative stress
has been associated with diabetes and hypertension, which are risk factors for
chronic kidney disease (CKD). However, it is unclear whether serum GGT is
independently associated with CKD. METHODS: We analyzed data from a population
based study of Appalachian adults residing in six communities in Ohio and West
Virginia, who were aged > or = 18 years (n = 55,187, 52% women). Serum GGT was
examined as gender-specific quintiles (quintiles 1-5 in women: 0-11 U/L, 12-14
U/L, 15-19 U/L, 20-29 U/L and > 29 U/L; quintiles 1-5 in men: 0-17 U/L, 18-23
U/L, 24-30 U/L, 31-45 U/L, and > 45 U/L). The main outcome of interest was CKD (n
= 4482), defined as an estimated glomerular filtration rate of < 60 mL/ min/1.73
m2 from serum creatinine. RESULTS: Higher serum GGT levels were not found to be
associated with CKD after adjusting for age, education, smoking, alcohol intake,
body mass index (BMI), diabetes, hypertension and total cholesterol. In women,
compared to quintile 1 of GGT, the odds ratio (OR) (95% confidence interval [CI])
of CKD associated with quintile 5 was 0.93 (0.82-1.06); p-trend = 0.3102.
Similarly, in men, compared to quintile 1 of GGT, the odds ratio (OR) (95%
confidence interval [CI]) of CKD associated with quintile 5 was 0.94 (0.80-1.10);
p-trend = 0.4372. Subgroup analyses that examined the relation between GGT and
CKD by alcohol intake and BMI categories also showed a consistent null
association. CONCLUSION: In a community-based sample of Appalachian adults,
higher serum GGT was not found to be independently associated with CKD.
PMID- 25134187
TI - Ectopic production of HCG by a benign ovarian mature cystic teratoma simulating
an extra-uterine pregnancy: a case report.
AB - Physicians should consider a benign mature cystic teratoma in their differential
diagnosis of a patient with an elevated serum human chorionic gonadotropin
concentration. BACKGROUND: Following tubal ligation, a woman with amenorrhea and
elevated serum human chorionic gonadotropin (HCG) concentrations may be
experiencing either an ectopic or an intrauterine pregnancy. Other sources of HCG
production can include ovarian germ cell tumors or gestational trophoblastic
disease such as a complete or partial molar pregnancy. A rare source of HCG
production is a benign mature ovarian teratoma. CASE: A 31-year old Gravida 2
para 2 presented with a positive home pregnancy test three years after she had
experienced a Pomeroy tubal ligation. Her serum HCG was 57,914 mlU/mL but a
transvaginal ultrasound did not find an intrauterine pregnancy. Laparoscopy was
performed due to a suspicion of an ectopic pregnancy and an 11-cm benign mature
cystic teratoma (dermoid cyst) within the right ovary was removed. An ectopic
pregnancy was not visualized. Post-operatively, her serum HCG levels decreased
and were negative within four weeks. CONCLUSION: Mature ovarian cystic teratomas
have rarely been reported to secrete HCG. They can be an infrequent source of HCG
production and may lead to emergency surgery to treat a suspected extra-uterine
pregnancy.
PMID- 25134188
TI - Gender and geographic differences in CAD risk factors and CHADS2 scores in atrial
fibrillation patients.
AB - Atrial fibrillation (AF) is a cardiac arrhythmia associated with a wide range of
other co-morbid medical conditions. The state of West Virginia has a higher
prevalence of coronary artery disease (CAD) and CAD risk factors compared to the
national average. We hypothesized that West Virginians with atrial fibrillation
would also have a higher prevalence of CAD risk factors and higher CHADS2 stroke
risk scores. This is particularly important since Louisiana is the only high CAD
risk southern state included in the original verification of the CHADS2 risk
scoring system (i.e. California, Connecticut, Louisiana, Maine, Missouri, New
Hampshire, and Vermont). Accordingly, we performed a retrospective analysis of
the association between AF and CAD, CAD risk factors and CHADS2 scores in a
cohort of men and women in the West Virginia University Hospital population. We
report a greater positive association between AF and hypertension, diabetes
mellitus and obesity than the national average. AF was seen more commonly among
men. But, CHADS2 scores were higher among women as a result of a higher
prevalence of diabetes mellitus. This study indicates that AF is associated with
a greater prevalence of CAD risk factors and higher CHADS2 scores among West
Virginians in comparison with the rest of the nation.
PMID- 25134189
TI - Identification of genes contributing to cardiovascular disease in overweight and
obese individuals from West Virginia.
AB - Excess weight is a known risk factor for coronary artery disease (CAD) and a
large percentage of overweight and obese individuals ultimately develop CAD. The
objective of this study was to identify human genes associated with CAD in a
subgroup of overweight and obese individuals using population-based association
methods. Logistic regression analyses were used to test the association between
single nucleotide polymorphisms (SNPs) in 34 candidate genes and the CAD
phenotype with age, gender, and BMI as covariates. Two SNPs in the Apolipoprotein
B (Apo B) gene [rs1042031 and rs1800479], one in the Cholesterol Ester Transfer
Protein (CETP) gene [rs5880], and one in the Low Density Lipoprotein Receptor
(LDLR) gene [rs2569538] met the 0.01 significance level for association with CAD.
Based on these findings, we conclude that variants within the CETP and Apo B
genes conferred susceptibility to CAD in overweight individuals and that a
variant with the LDLR gene conferred susceptibility in an obese group.
PMID- 25134191
TI - In with the new.
PMID- 25134190
TI - Strongyloides hyperinfection syndrome complications: a case report and review of
the literature.
AB - Strongyloidiasis is a major global health challenge that is often underestimated
in many countries. In immuno-compromised hosts, an autoinfection can go unchecked
with large numbers of invasive Strongyloides larvae disseminating widely and
causing hyperinfection, with fatal consequences. This review will highlight a
case of gram negative bacteremia complicated by meningitis and Adult Respiratory
Distress Syndrome (ARDS) as a fatal outcome of Strongyloides hyperinfection,
commonly known to occur in the setting of immunosuppression. A middle aged female
with chronic lymphocytic leukemia and hypogammaglobulinemia presented with severe
respiratory distress requiring intubation. She had been on intermittent
corticosteroids and multiple courses of antibiotics for the past six months for
COPD exacerbations. Bronchoalveolar lavage showed Strongyloides stercoralis.
Blood cultures grew Vancomycin Resistant Enterococci and a few days later
Vancomycin Sensitive Enterococcus was found in the CSF. Afterwards, she grew
Vancomycin Sensitive Enterococcus in the blood. She was treated with Ivermectin
and Albendazole for Strongyloides and Linezolid and Vancomycin for these two
different strains of E. faecium. After initial resolution of bacteremia and
meningitis, she relapsed three weeks later with the same organism growing in the
CSF. The clinical course continued to deteriorate with the development of
significant neurological dysfunction. Poor nutritional state and ventilator
associated pneumonia contributed to this downward trend. After a detailed
discussion with the family, life support was discontinued and the patient
succumbed to her illness.
PMID- 25134192
TI - WVU Healthcare welcomes new heart surgeon. Dr. Anthony Holden Joins WVU Heart
Institute.
PMID- 25134193
TI - WVU Healthcare offers new lung cancer screening program.
PMID- 25134194
TI - Meaningful use--becoming a "meaningful user".
PMID- 25134195
TI - Translational Genomic Research Institute dedicated.
PMID- 25134197
TI - Disability insurance: residual/recovery benefit.
PMID- 25134196
TI - Nanoparticles in fuel additives associated with liver damage.
PMID- 25134198
TI - Chains and other choices.
PMID- 25134199
TI - Induction. NHS can scrimp and save on medicines.
PMID- 25134200
TI - Workforce. Pharma on the front line.
PMID- 25134201
TI - Workforce. Why the key to people is planning.
PMID- 25134202
TI - Patient safety: case studies. Turning confusion to clarity.
PMID- 25134203
TI - Clinical care protocols. When safe comes as standard.
PMID- 25134204
TI - On protecting whistleblowers. The NHS needs a staff support commission.
PMID- 25134205
TI - Stevens will draw the poison from NHS leadership.
PMID- 25134206
TI - Electronic records are vital.
PMID- 25134207
TI - Older people's services. Japan's vision of a 'total care' future looks bright.
PMID- 25134208
TI - Essay competition. Emerging leaders put pen to paper.
PMID- 25134209
TI - Training. Fuel the fire of new leaders' ambitions.
PMID- 25134210
TI - Hobby Lobby ruling may spur shift away from employer coverage.
PMID- 25134211
TI - Justices side with health workers who object to paying union fees.
PMID- 25134212
TI - Earnings outlook good for publicly traded hospital companies.
PMID- 25134213
TI - McDonald faces steep learning curve in running troubled VA, insiders say.
PMID- 25134214
TI - Wave of consolidation rumbles toward academic medical centers.
PMID- 25134215
TI - New facility design aims for greater safety, efficiency.
PMID- 25134216
TI - Where history happened: hospital treated Kennedy.
PMID- 25134217
TI - Benefits unclear as states rush into Medicaid managed care.
PMID- 25134218
TI - Hobby Lobby's blow to employer-based health insurance.
PMID- 25134219
TI - Building consensus on what really counts.
PMID- 25134220
TI - Advancing a medical home for surgical services.
PMID- 25134221
TI - Targeting the right patients for support.
PMID- 25134222
TI - Timing, earlier setbacks helped Obamacare pass: Jennings.
PMID- 25134223
TI - What your nurse needs to know about genetics.
PMID- 25134224
TI - Transition of pediatric patients to adult care: an analysis of provider
perceptions across discipline and role.
AB - The importance of successfully transitioning pediatric patients to adult care is
increasingly recognized as more children with chronic diseases are living to
adulthood. The aim of this study was to investigate the current state of provider
perceptions across disciplines regarding transition of pediatric patients to
adult care. Focus groups made up of providers of various roles and experience
levels were conducted. A total of six major themes were identified. We conclude
that pediatric providers share common concerns about transitioning pediatric
patients to adult care. We reinforce many of the issues raised in the literature
and also discuss a sense of professional ego that was identified as a barrier to
successful transition, which is not widely reported in other studies.
PMID- 25134225
TI - Newborn morbidities and health charges: the first eight weeks.
AB - Recent health care legislative acts, federal budget cuts, and changes in health
care reimbursement are posing significant challenges for mothers accessing health
care for their infants. There is very little reported literature on post-birth
newborn morbidity and associated charges for full-term infants within the first
two months of life, a time of increased risk for mortality. PURPOSE: To examine
infant morbidities, associated health care charges, and access to health care
within the first eight weeks in healthy, full-term infants born to low-income,
first-time mothers. DESIGN: A secondary analysis of data from a randomized
clinical trial that compared infants' health and newborn health care charges.
METHODS: Data on infant morbidity and health care charges on 139 first-time
mothers and their healthy full-term newborns were collected at one and two months
post-hospital discharge. Data were analyzed using descriptive statistics and two
sample t-tests. FINDINGS: The most common infant morbidity was upper respiratory
illness. Morbidities occurred as early as day two post-hospital discharge. Total
charges were emergency room visits--$24,255, urgent care visits--$2,937, and
rehospitalizations--$56,377. Most newborns received a well-baby clinic visit
within 48 to 72 hours post-hospital discharge. CONCLUSION: Studies of
morbidities, health care charges, and access to care for infants two months and
less are very limited. However, such data are important because of increasing
health care costs, health care budget cuts, and the lack of an infant morbidity
surveillance system.
PMID- 25134226
TI - Inpatient falls in freestanding children's hospitals.
AB - Patient falls are considered a significant safety risk, but little evidence
regarding the significance of falls in children is available. A multisite,
observational study of fall events occurring in pediatric inpatients (younger
than 18 years of age) from Child Health Corporation of America member hospitals
was conducted to determine the prevalence and significance of falls. Fall
prevalence was 0.84 per 1,000 patient days with 48% classified as preventable.
Injuries occurred in 32%, but only two falls resulted in an increased length of
stay; none resulted in permanent disability or death. Only 47% of the children
who fell were identified to be at risk for fall. Alert mechanisms were used in
60% and preventive measures in 23%. These findings suggest that while inpatient
pediatric fall rates are lower than those of adults, greater diligence in
identification and risk reduction may further reduce the prevalence of falls and
the proportion of fall-related injuries.
PMID- 25134227
TI - 'Everyone knows' vs. finding the data.
PMID- 25134228
TI - Clinical relevance of the Humpty Dumpty Falls Scale in a pediatric specialty
hospital.
AB - The Joint Commission requires pediatric hospitals to implement fall prevention
programs and evaluate the efficacy of such programs. The Humpty Dumpty Falls
Scale (HDFS), a seven-item assessment scale used to document age, gender,
diagnosis, cognitive impairments, environmental factors, response to
surgery/sedation, and medication usage, is one of several instruments developed
to assess fall risk in pediatric patients. To determine the specificity and
sensitivity of the HDFS in predicting falls in children hospitalized for
pediatric specialty care, a team at a pediatric specialty hospital conducted a
nonexperimental retrospective study that used a matched case-control design and
chart review analysis. The discoveries suggest that the HDFS lacks accuracy in
pediatric specialty patients. Using the HDFS cut-off score of 12 and above to
indicate a high risk for falls in these children yields a high false-positive
rate. Investigators and staff at pediatric specialty hospitals need to continue
their pursuit of valid instruments and tools that contribute to fall reduction.
PMID- 25134229
TI - Validation: a family-centered communication skill.
AB - Family-centered care can seem challenging when family member behavior, choices,
attitudes, or emotions are "difficult" or "challenging" to deal with. Yet nurses
can develop skills to effectively interact with families in a wide variety of
circumstances and then become able to practice family-centered care in any
situation that might arise. One particularly useful skill is "validation," which
means accepting what the family member says or does as a valid expression of
thoughts and feelings in that particular circumstance at that particular time.
Validation does not mean there is agreement or acceptance of unsafe behaviors,
only that the nurse acknowledges that the family member's concerns and feelings
are important and should be listened to and taken seriously, even in the presence
of disagreement. Validation, which should be individualized, can take many forms,
ranging from providing complete attention to reflection of statements,
identification of possible unexpressed emotions, normalization, and finally, a
full and genuine sense of connection. Understanding and practicing validation can
empower nurses and family members, as well as support effective family-centered
communication and problem solving, even in challenging circumstances.
PMID- 25134230
TI - Promoting positive pediatric experiences for nursing students at the Children's
Hospital of Pittsburgh of UPMC.
AB - Challenges in professional nursing education today can be astonishing. Cognizant
of the commitment to provide the most valuable learning experiences for our
future nurses, academia and service organizations strive to meet this challenge.
The escalation in nursing school enrollment, along with the increase in patient
acuity and ongoing health care changes, requires hospitals and schools to
continually review their practices to ensure positive outcomes. Providing
pediatric nursing experiences to over 1,300 students annually, Children's
Hospital of Pittsburgh of the University of Pittsburgh Medical Center (UPMC)
implemented a process to meet this need. A Faculty Advisory Council was
established to provide a venue for representative nursing instructors to meet
with the Nursing Education Department at the hospital. The commonality of focus
by nursing faculty and Children's Hospital continues to strengthen both academia
and service. This well-defined process supports positive pediatric experiences
for nursing students at Children's Hospital of Pittsburgh of UPCM.
PMID- 25134231
TI - Mitochondrial disease in children and adolescents.
PMID- 25134232
TI - Message from the president.
PMID- 25134233
TI - Right-sizing care: promoting sensitivity to a growing population.
PMID- 25134234
TI - A job to serve others.
PMID- 25134236
TI - 'All of a sudden, there was fire'.
PMID- 25134235
TI - Building and sustaining a caring-based nurse-managed center.
PMID- 25134237
TI - Investments counteract low margins.
PMID- 25134238
TI - Devicemaker consolidation likely to continue.
PMID- 25134239
TI - 'It's not pretty': could UPMC, Highmark feud be an omen for markets entering
consolidation?
PMID- 25134240
TI - Small-business exchanges off to rocky start.
PMID- 25134241
TI - Preventing readmissions: is there an app for that?
PMID- 25134242
TI - Data collection could stump next phase of predictive analytics.
PMID- 25134243
TI - Wachter, McClellan offer takes on measuring quality.
PMID- 25134244
TI - Better rules needed to boost use of big data.
PMID- 25134245
TI - In ACO era, physicians will still play a leading--but changing--role.
PMID- 25134246
TI - Make hospital visiting hours 24/7.
PMID- 25134247
TI - CHI seeks integration in all directions, including insurance.
PMID- 25134248
TI - "Docile bodies" or "impudent" women: conflicts between nurses and their
employers, in England, 1880-1914.
PMID- 25134249
TI - Conflicting chains of command in Dutch Catholic nursing (1839-1966).
PMID- 25134250
TI - Fighting for one's own health--care as a cause of illness.
PMID- 25134251
TI - [The day-to-day routine in hospitals--standards and conflicts, based on the
example of the Rothschild spital in Vienna around the year 1900].
AB - The juxtaposition of official regulations and letters of complaint from Vienna's
Rothschild Hospital shows, beyond the rhetoric and euphemisms of hospital
reports, how lively and diverse day-to-day life was in a Jewish hospital around
the year 1900. The letters of complaint query the official hospital rules and
show that ideal and reality did not always coincide. Often, religious questions
were at the root of the critique--such as doubts as to whether kosher dietary
laws were adhered to--or conflicts between the agents involved, be they
individuals or groups, patients, nurses, physicians or administrative staff. As
part of this process, power structures, social hierarchies, patient rights and
gender issues were called into question and renegotiated.
PMID- 25134252
TI - [Parish nursing around the year 1900].
AB - This contribution first introduces the factors that supported the development of
parish nursing before going on to explain the diverse organizational concepts
involved and their development over time. It looks at the various Catholic and
Protestant as well as secular institutions active in this field. The article then
discusses the manifold tasks, fields of work and approaches to problem-solving
that were characteristic of parish nursing. The various cultural, social and
religious problems that the parish nurses had to contend with on a daily basis
are also presented, including the increasing competition with other professional
groups. The article concludes by looking at the standing of parish nurses in
society and the advantages and disadvantages of parish nursing as opposed to
hospital nursing from the point of view of the parish nurses themselves.
PMID- 25134253
TI - ["Practical tuberculosis care outside the hospital stands and falls with the
tuberculosis nurse". Challenges in out-patient care, using the example of
tuberculosis nurses in the first third of the 20th century].
AB - Once it had become apparent that tuberculosis sanatoriums were unable to stop
this widespread disease, out-patient tuberculosis clinics were established for
patients and their relatives in the German Reich. These clinics, which started in
the late nineteenth century, employed physicians and tuberculosis nurses. The
nurses were generally community or parish nurses, specialized carers not being
trained until later. On the one hand, their tasks included the work at these
clinics, where they assisted the physician, admitted patients and carried out x
rays and lab tests. On the other hand--and this was their main task--they visited
the sick and their families at home, informed them about tuberculosis, instructed
them on questions of hygiene and the appropriate behaviour and made sure these
instructions were adhered to. If they were able to offer material help as well,
they were received more willingly--and they could only make their visits with a
patient's consent. Due to the lack of tuberculosis medicines, the work of the
tuberculosis nurses was a mainstay in the fight against this highly infectious
disease. They often had to overcome the resistance of general practitioners and
also of some patients and their families. But they loved doing their job because
they were appreciated by the tuberculosis doctors, had a relatively high degree
of freedom, authority and responsibility as health visitors and achieved visible
results through personal commitment.
PMID- 25134254
TI - ["They are enjoying their first holiday ever"--working with the elderly, from the
post-war years up to the early 1970s].
AB - While, in the post-war years and into the 1950s, the building of old people's and
care homes and the allocation of home places in those homes was seen as the main
task of municipal care institutions for the elderly in Frankfurt am Main, in the
decade that followed their main task shifted towards increasing the possibilities
of providing care in people's own homes, delaying the move into old people's
homes and breaking through the loneliness that elderly people were presumed to
experience. Supported by the state, community housing was provided with flats for
elderly people and with carers to look after their needs. The "warm rooms" of the
post-war period changed into clubs, where members met and received guidance. In
the late 1960s the clubs were extended into day-care centres, offering a range of
consultation services, organized day trips and recreational holidays for the
elderly. It was hoped that "meals-on-wheels" in combination with age-appropriate
living conditions would delay the move into a home. But these plans were not
adequately developed in the 1960s and often it was not clear who would pay the
bills. The same was true of outpatient medical care which had traditionally been
the task of community nurses, but was now increasingly carried out by local
authority carers, who also provided household assistance. This kind of care could
only ever be given for a limited period of time and, while it was able to delay
the move into an old people's home, it could not replace it.
PMID- 25134255
TI - [The "secret book" of Dr Friedrich Benjamin Osiander: anonymous births in the
Gottingen Accouchierhaus, 1794-1819].
AB - The problem of anonymous or confidential deliveries, a subject of current
controversy, has a long history. Some maternity hospitals offered the possibility
for "clandestine" births as early as the 18th and 19th century. A recently
emerged source about the maternity clinic of Gottingen University allows insight
into the motives that led to keeping a birth secret and the consequences of such
a clandestine birth for mother, father and child. The director of the
institution, a professor of obstetrics, wrote case reports on the women, who paid
a handsome sum for his help and the in-patient care they received. In return,
these women could be admitted under a pseudonym, and thus falsify their child's
birth certificate; moreover they were not used as teaching material for medical
students and midwife apprentices, whereas "regular" patients had to give their
names and, in return for being treated free of charge, be available for teaching
purposes. The ten cases that have been painstakingly investigated reveal that the
reasons that led the women and men to opt for an anonymous birth were manifold,
that they used this offer in different ways and with different consequences. All
of these pregnancies were illegitimate, of course. In one case the expectant
mother was married. In several cases it would be the father who was married. Most
of the women who gave birth secretly seem to have given the professor their
actual details and he kept quiet about them--with the exception of one case where
he revealed the contents of the case report many years later in an alimony suit.
Only one of the men admitted paternity openly, but many revealed their identity
implicitly by registering the pregnant woman or by accompanying her to the
clinic. If the birth was to be kept secret the child needed to be handed over to
foster parents. By paying a lump sum that covered the usual fourteen years of
parenting, one mother was able to avoid any later contact with her son. In most
cases contact seems to have been limited to the payment of this boarding money.
One of the couples married later and took in the twins that had been born
clandestinely out of wedlock. One mother kept close contact with her son through
intermediaries. All of the women who gave birth in this clandestine fashion
received practical as well as financial support, often from the child's father or
from a relative. Few of them came by themselves. In those days, only women who
used the maternity hospital free of charge would have been as isolated in the
difficult perinatal period as are women today who choose to deliver their babies
anonymously.
PMID- 25134256
TI - [A ''humanitarian duty and a matter of honour for German Jewry": "feeble-minded"
Jewish children and the Institution in Beelitz].
AB - In 1908, in collaboration with the Bnei Briss, the German Association of
Israelite Communities founded an institution for intellectually disabled Jewish
children in Beelitz with the aim of educating 7-14-year-olds, using therapeutic
pedagogy. The institution was part of the philanthropic efforts undertaken by
German Jewry in that period. It was set up in the wake of the German Kaiser's
call to found more philanthropic institutions, and its establishment is
indicative of the efforts at integration being made by German Jewry. In their
fund-raising material, the German Association of Israelite Communities stressed
the "loyalty and patriotism" of German Jewry and described the establishment of
the institution as "a humanitarian duty" and "a matter of honour for German
Jewry". It was, therefore, demands from the non-Jewish world that led to the
foundation of a Jewish institution; however, its establishment was also symbolic
of the struggle against anti-Semitism and indicative both of German Jewry's
dissimilation and their efforts at integration. The article investigates the
struggle of Jewish parents to have their children admitted to the institution,
the philosophy and teaching methods of the director Sally Bein (1881-1942) and
his wife Friederike Rebeka Bein (1883-1942), the background of the students, the
causes of intellectual disability, as well as the disagreements that occurred
between parents, teachers and the director. The article also discusses the
successes and failures of therapeutic pedagogy.
PMID- 25134257
TI - [Deaf Jews in Germany, 1800-1933. A look at the history of a dual minority].
AB - This study examines the importance of religious denomination in the German
community of deaf people in the 19th century and up until 1933, focusing on the
dual minority status of deaf Jews. It shows that the educational system for the
deaf and the deaf movement as such were, in structure and content, informed by
the Christian, primarily the Protestant, faith. This meant that deaf Jewish
people were in danger of facing a conflict between their identity as Jews and
their identity as deaf people. In order to resolve this dilemma, Jewish
philanthropists and deaf people created a range of complementary structures:
schools where deaf Jewish children received tuition tailored to their needs,
religious services in sign language and a Jewish deaf association for mutual
support and companionship. But being members of two stigmatized and marginalized
groups made the Jewish deaf vulnerable from several sides. The discursive
association of deafness, Judaism and heredity played a particular part in this.
This study comes to the conclusion that deaf Jews did not want to choose between
their deaf and Jewish identities but they wanted to belong to both. As a result
they suffered from the negative views that some deaf people had of Jews and some
Jews of deaf people--as well as from the double discrimination by the mainstream
society.
PMID- 25134258
TI - [The flu epidemic after World War I and homeopathy--an international comparison].
AB - The "Spanish Flu" began in 1918 and was the most devastating pandemic in human
history that had ever been, claiming more lives than World War I. The flu virus
had not yet been discovered, and the usual therapy measures were merely
symptomatic. In many parts of the world the pandemic was treated by homeopaths.
At the time, homeopathic medical practices, out-patient clinics and hospitals
existed in various countries. To this day homeopaths refer to the successful
homeopathic treatment of the "Spanish Flu". The following paper looks at what
this treatment consisted in and whether it was based on a particular concept. It
also examines contemporary evaluations and figures, as well as the question as to
whether homeopathy experienced a rise in demand as a consequence of its success
during the pandemic.
PMID- 25134259
TI - Rethinking leadership development.
PMID- 25134260
TI - The surgery panel in Diego Rivera's Detroit Industry Murals.
PMID- 25134261
TI - Vital amines, purple smoke. A select history of vitamins and minerals.
PMID- 25134263
TI - The mysterious illness of Emma Lazarus, Lady Liberty's poet.
PMID- 25134262
TI - An obstetric story.
PMID- 25134264
TI - The most memorable patient I never saw.
PMID- 25134265
TI - Fall from grace.
PMID- 25134266
TI - Dr. Marr responds to Dr. Volpintesta.
PMID- 25134267
TI - Fall from grace.
PMID- 25134268
TI - Fall from grace.
PMID- 25134269
TI - Dr. Marr responds to Dr. Sprecace and Dr. Spaeth.
PMID- 25134270
TI - Experts: know your patients' benefits and work to conserve them.
AB - Case managers should know their patients' insurance benefits and out-of-pocket
expenses when they develop a discharge plan to make sure the patient can afford
the plan they are putting in place. Take policy limitations into account and
preserve benefits for their future needs. Look for community resources such as
medication assistance plans and clinics that charge a sliding scale when patients
don't have coverage for needed services. Make sure patients and family members
understand the benefits when they make choices about post-acute care.
PMID- 25134271
TI - Being creative when benefits are maxed out.
PMID- 25134272
TI - Knowing benefits helps patients make choices.
PMID- 25134273
TI - Audits highlight need for documentation.
AB - The Centers for Medicare & Medicaid Services' "Probe and Educate" initiative to
determine hospitals'compliance with the two-midnight rule makes it clear that
case managers must review physician documentation as well as medical necessity.
The Medicare Administrative Contractors are focusing on short stays when
physician documentation doesn't support the expectation of a two-midnight stay.
They're looking at flawed admission orders, and when the orders to admit are
issued by a practitioner who does not have admitting privileges at the hospital.
Another area of focus is physician statements without documentation of the reason
for the need for inpatient treatment.
PMID- 25134274
TI - Visual cues keep treatment team alert.
AB - At Good Samaritan Medical Center in West Palm Beach, FL, a throughput initiative
that uses colored magnets to indicate anticipated discharges has cut emergency
department holding time and increased the number of discharges by 2 p.m. The
charge nurse, case manager, and discharge planner meet daily, make their best
clinical guess about the patient's discharge and place a red, yellow, or green
magnet on a white board at the nurses station. When team members pass the board,
they are alerted to anticipated discharges and know to make patients with a green
magnet a priority. The case managers and nurses write the expected discharge on a
white board in the patient rooms and initiate a discussion with patients and
family members to prepare them for discharge.
PMID- 25134276
TI - Heart failure program cuts readmission rate.
PMID- 25134275
TI - Case management insider. Family caregivers: a key component of the discharge
planning process.
AB - The role of the family caregiver may not be for a short time period. It could go
on for months or even years. As case managers, our role is to ensure that we have
provided our family caregivers with all the information that they may need to
care for their loved one at home or in another care setting. This will take some
time, but it is time well spent and will reduce the likelihood that an
unnecessary trip to the emergency room will take place. Remind caregivers to know
their strengths, limitations and to always be flexible!
PMID- 25134277
TI - Decreasing preventable readmissions?
AB - Bioethicists can advocate for improved communication with family caregivers when
a patient is going to be discharged from the hospital. Healthcare providers are
often unaware of a family member's inability to provide needed care. Many
patients who access "safety-net" public hospitals have worse outcomes of
hospitalization, including readmissions. Bioethicists can advocate for more
partnerships between hospitals and community-based programs.
PMID- 25134279
TI - Pregnancy outcome after laparoscopic myomectomy.
AB - PURPOSE OF INVESTIGATION: Main purpose of this study was to analyze the
reproductive and obstetrical outcome as delivery mode and incidence of major
complications (uterine bleeding and uterine rupture) after laparoscopic
myomectomy. MATERIALS AND METHODS: The authors conducted an observational study
in patients who underwent laparoscopic myomectomy. Inclusion criteria were:
surgery performed for single and or multiple myomas sized between five and 15 cm
and pregnancy desire. Exclusion criteria were: surgery for pedunculated myomas
and male or tubal infertility. Collected data on pregnancy desire, success in
obtaining pregnancy surgical interval time before pregnancy, performing assisted
reproductive medicine, gestational weeks, mode of delivery, indicating a possible
cesarean section, and complications. On collected data the authors calculated
pregnancy and abortion rates. RESULTS: Among patients aged between 19 and 42
years who answered a telephonic questionnaire, the authors selected 185 patients
with pregnancy willing. A total number of 426 myomas were removed; 115 (62.2%)
patients reported 151 pregnancies, nine in a total of 17 patients achieved it
with reproductive assistance, 38 pregnancy ended in abortion, and two had an
ectopic implantation. The authors finally reported 111 successful pregnancy, with
seven preterm deliveries (6.3%). Mode of delivery had been cesarean section in 69
cases (63.4%) and vaginal delivery in 42 cases (36.6%), with a respective mean
interval time between surgery and delivery of 24.6 +/- 20.0 months and 19.2 +/-
13.3 months. CONCLUSION: Laparoscopic myomectomy proved to be an effective
procedure feasible for women who wish to become pregnant with a subsequent good
reproductive outcomes, both in terms of pregnancy and abortion rates that were
comparable with the literature. If laparoscopic suturing of the fovea myometralis
is adequate, there are no contraindications for vaginal delivery, regardless of
the patient's age, the number, size, and location of the myomas removed.
PMID- 25134278
TI - Serum markers of oxidative stress and endometriosis.
AB - PURPOSE OF INVESTIGATION: To assess the changes secondary to chronic inflammation
in women with and without pelvic endometriosis by the determination of serum
thiols and carbonyls. MATERIALS AND METHODS: Sixty-seven women with endometriosis
consecutively submitted to laparoscopy and 41 women without endometriosis
consecutively submitted to tubal ligation (control group) were selected. Serum
levels of total thiols and carbonyls were determined in both groups. RESULTS:
Patients with endometriosis had significantly lower thiol levels than controls
(342.37 +/- 142.09 microM vs 559.60 +/- 294.05 microM) (p < 0.001), as well as
significantly lower carbonyl levels (8.97 +/- 3.76 microM vs 16.40 +/- 9.26
microM) (p < 0.001). Other clinical characteristics were not associated with
changes in marker levels. The cutoff point established by the ROC curve was
396.44 microM for the thiols, with 73.1% sensitivity and 80.5% specificity, and
14.9 microM for the carbonyls, with 94% sensitivity and 51.2% specificity.
CONCLUSIONS: The serum thiol levels revealed an increase in oxidative stress
related to the development of pelvic endometriosis.
PMID- 25134280
TI - Predictive value of fetal fibronectin on the embryonic loss of patients with
recurrent spontaneous abortion in early pregnancy.
AB - OBJECTIVE: This work aims to investigate the predictive value of fetal
fibronectin (fFN) in embryonic loss of patients with recurrent spontaneous
abortion (RSA) in early pregnancy. MATERIALS AND METHODS: Eighty-four patients
with RSA in early pregnancy were selected as the test group and 31 healthy women
in early pregnancy were selected as the control group. The ages and number of
previous abortions, along with other information, were recorded. These patients
underwent a fFN test, and their pregnancy outcome was followed up until 14 weeks.
RESULTS: The incidence of spontaneous abortion was 20.24% in the test group and
9.68% in the control group. The positive fFN [fFN (+)] rate was 57.14% in the
test group and 12.90% in the control group, indicating a statistically
significant difference (p < 0.01, chi2 = 17.89). The incidence of spontaneous
abortion was 29.17% (14/48) in the fFN (+) group and 8.33% (3/36) in the fFN (-)
group, indicating a statistically significant difference (p < 0.05, chi2 = 5.53).
The sensitivity, specificity, and positive and negative predictive values in the
prediction of abortion in fFN (+) patients of the test group were 82.35%, 49.25%,
29.17%, and 91.67%, respectively. CONCLUSION: If detected at an early stage of
pregnancy, fFN in patients with RSA is largely related to the prediction of
abortion and facilitates the evaluation of pregnancy outcomes.
PMID- 25134281
TI - Microdose flare-up vs. flexible-multidose GnRH antagonist protocols for poor
responder patients who underwent ICSI.
AB - PURPOSE: To compare the performance of microdose flare-up (MF) and flexible
multidose gonadotropin-releasing hormone (GnRH) antagonist protocols in poor
responder patients who underwent intracytoplasmic sperm injection (ICSI).
MATERIALS AND METHODS: One hundred and 12 consecutive patients (217 cycles)
suspected to have poor ovarian response were enrolled. Group 1 (MF GnRH agonist
group) constituted 64 patients (135 cycles) who underwent MF GnRH agonist
protocol. Group 2 (flexible-multidose GnRH antagonist group) constituted 48
patients (82 cycles) who underwent flexible-multidose GnRH antagonist protocol.
RESULTS: The duration of stimulation (d) (11.5 +/- 2.1 vs. 10.4 +/- 2.7, p <
0.01) and the total dose of gonadotropin used (IU) (5,892.9 +/- 1,725.7 vs.
4,367.5 +/- 1,582.1, p < 0.05) were significantly lower in Group 2 when compared
to Group 1. The numbers of retrieved oocyte-cumulus complexes (4.5 +/- 3.6 vs.
5.9 +/- 4.9, p < 0.05), metaphase II oocytes (3.6 +/- 3.1 vs. 4.9 +/- 4.2, p <
0.05), two pronucleated oocytes (2.6 +/- 2.3 vs. 4.0 +/- 3.4, p < 0.05), the
number of available embryos at day 3 (2.6 +/- 2.2 vs. 4.2 +/- 3.2, p < 0.05) and
the rate of embryos with > or = seven blastomeres and < 10% fragmentation at day
3 (35.9% vs. 65.1%, p < 0.05) were significantly lower in Group 1 when compared
to Group 2. The number of embryos transferred (2.2 +/- 1.3 vs. 2.4 +/- 0.9), the
clinical pregnancy per embryo transfer (16.3% vs. 25.8%), and the implantation
rate (8.6% vs. 12.2%) were comparable between groups. CONCLUSIONS: Although the
flexible-multidose GnRH antagonist protocol produced better oocyte and embryo
parameters, the clinical pregnancy rate and the implantation rates were
comparable between the flexible-multidose GnRH antagonist and MF protocols in
poor responder patients.
PMID- 25134282
TI - Computerized in vivo classification of methylene blue stained fallopian tube
mucosal damage: preliminary results.
AB - OBJECTIVE: Fertiloscopy is a simple minimal invasive method which allows
salpingoscopy and microsalpingoscopy in order to examine the mucosa of the
fallopian tubes of patients with unexplained infertility. Infectious tubal damage
is a common cause of tubal infertility. In 1998 it was demonstrated that nuclear
staining of cellular nuclei during microsalpingoscopy with methylene blue
provides a simple in vivo method to evaluate cellular damage of the tubal
epithelium. The purpose of this study was to introduce and statistically test a
new computerized method to objectively evaluate the extent of tubal damage.
DESIGN OF RETROSPECTIVE STUDY: Cooperation of two Departments of Gynecology and
Obstetrics (Krankenanstalt Rudolfstiftung, Vienna, Austria and CRES Center,
Hopital Natecia, Lyon, France) with the University of Art and Design, Linz,
Austria and University Hospital, Vienna, Austria. MATERIALS AND METHODS:
Microsalpingoscopic images from ten female patients, aged between 18 and 45 years
with primary infertility, showing stained nuclei in damaged intrafallopian tubal
epithelium were provided by Antoine Watrelot, CRES Center, Hopital Natecia, Lyon,
France. These images were evaluated by an experienced medical expert staff
examiner and a computerized standard method called cross-correlation and template
matching. The obtained numbers of nuclear stainings were statistically evaluated.
RESULTS: Computerized evaluation of nuclear staining of damaged intrafallopian
epithelial cells in female patients with infertility obtains similar but more
reproducible results compared to manual evaluation (p = 0.007). CONCLUSION:
Normalized cross-correlation can be used to measure tubal damage diagnosed by in
vivo methylene blue dyeing during microsalpingoscopy and might facilitate the
decision for in vitro fertilisation in patients with unclear unexplained
infertility in further studies.
PMID- 25134283
TI - Study of urotensin II gene and serum levels in relation to pre-eclampsia.
AB - OBJECTIVE: To verify the relationship between Urotensin II (UII) gene and serum
levels and pre-eclampsia (PE). STUDY DESIGN: Prospective case control study.
SETTING: Tertiary Obstetric centre and university hospital. SUBJECTS: A total of
80 pregnant women at their third trimester were included, 30 of which were with
mild PE, 30 with severe disease and 20 age- and BMI-matched normotensive pregnant
women (controls). MATERIALS AND METHODS: UII gene polymorphism as well as UII
serum levels were assessed and compared in patients vs. control. RESULTS: No
difference was seen between the groups in terms of age or parity at the time of
recruitment. A statistically significant difference in the Urotensin II genotype
frequencies between patients and control groups was found. The mean serum UII,
also showed a significant difference between the studied groups, and control
group. Comparing the observed and expected values of UII genotype frequencies in
mild, severe PE, and in controls, no significant difference was noted in the homo
mutant, the hetero-mutant or the wild genotypes. CONCLUSIONS: Elevation of UII in
the serum of PE patients could be correlated to the severity and/or progression
of the disease. The UII genotype frequencies between patients and control groups
showed a significant difference, which implies a potential benefit for UII gene
or level in serum as a diagnostic or prognostic indicator in pre-eclampsia.
PMID- 25134284
TI - Effect of gestational weight gain as well as rehabilitation training on postnatal
pelvic muscle strength.
AB - OBJECTIVE: The current study explored the impact of gestational weight gain on
postnatal pelvic muscle strength and the effect of low-frequency electrical
stimulation combined with biofeedback training on strength recovery. MATERIALS
AND METHODS: A total of 126 mothers six to eight weeks after term delivery were
recruited at Peking University Shenzhen Hospital from August 2010 to July 2011.
According to gestational weight gain, they were divided into two groups: the < 15
kg (A) and > or = 15 kg (B) groups. Pelvic floor muscle fibre strength was
determined. Target low-frequency electrical stimulation combined with biofeedback
training was conducted. After training, pelvic floor muscle fiber strength was
determined again for effect evaluation. RESULTS: Before training, types I and II
pelvic floor muscle fiber strength of group B was noticeably lower than that of
group A (p < 0.05). After rehabilitation, the pelvic floor muscle strength of
both groups significantly increased (p < 0.05). However, types I and II pelvic
floor muscle fiber strength of group B was still significantly lower than that of
group A (p < 0.05). CONCLUSION: Gestational weight gain negatively influences
pelvic floor muscles. Low-frequency electrical stimulation combined with
biofeedback training improves postnatal pelvic floor muscle fiber strength. A
less gestational weight increase indicates faster postnatal pelvic muscle
strength recovery and a better rehabilitative effect.
PMID- 25134285
TI - Sublingual misoprostol is better for cervical ripening prior to hysteroscopy in
post-menopausal women.
AB - BACKGROUND: The aim of the present study was to evaluate the efficacy of
misoprostol administered sublingually, vaginally or rectally on cervical ripening
before hysterescopic surgery in post-menopausal women. MATERIALS AND METHODS:
Post-menopausal women were randomised to receive either 400 ug of misoprostol,
administered sublingually, vaginally or rectally six hours and 12 hours prior to
operative hysterescopy. RESULTS: Patients were randomized to receive receive
sublingual (n = 30), rectal (n = 30) or vaginal (n = 30) misoprostol. The control
group did not receive misoprostol (n = 30). The four groups were comparable in
terms of preoperative cervical width after misoprostol administration. The mean
cervical widths for control group was 9.0 +/- 1.1 mm and the mean post-treatment
cervical widths for the sublingual, vaginal, and rectal groups were 7.1 +/- 1.1
mm, 8.9 +/- 1.3 mm, and 8.6 +/- 1.5 mm, respectively. The cervical widths of
sublingual group were significantly different from control, vaginal; and rectal
groups (p < 0.001). CONCLUSION: Four hundred micrograms of sublingual
misoprostol, 12 and six hours prior to operative hysteroscopy has a significant
cervical ripening effect compared with vaginal, rectal, and control groups in
post-menopausal women.
PMID- 25134286
TI - Thermal balloon ablation versus transcervical endometrial resection: evaluation
of postoperative pelvic pain in women treated for dysfunctional uterine bleeding.
AB - PURPOSE OF THE STUDY: To evaluate postoperative pain after mini-invasive surgical
treatment for dysfunctional uterine bleeding (DUB) with transcervical endometrial
resection or thermal ablation balloon. MATERIALS AND METHODS: A longitudinal
observational study, analyzing 47 women affected by DUB who underwent endometrial
ablation was conducted. The authors collected evaluation of pelvic pain at one
and four hours after intervention and the individual necessity of analgesics.
After 30 days, all patients underwent a gynecological visit to evaluate
postoperative outcome. RESULTS: Pelvic pain was higher one and four hours after
procedure in thermal balloon ablation group, and patients in the same group
required more analgesic rescue dose. There were no complications such as uterine
perforation, heavy blood loss or thermal injuries with both the procedures.
CONCLUSION: Thermal balloon ablation appears a more painful procedure than
endometrial resection, both in the immediate postsurgical time and 30 days after
surgery. Ad hoc anaesthesiologic and analgesic protocol should be adopted to
ensure quick recovery and good acceptance of the procedure.
PMID- 25134287
TI - Is there any association between mild hypertension and hot flash experience among
women?
AB - OBJECTIVE: To determine the association between ambulatory blood pressure (ABP),
heart rate, and hot flash (HF) experience among women. MATERIALS AND METHODS: The
authors recruited 110 women aged 22 to 65 years with mild essential hypertension
or normotension confirmed by 24-hour ABP monitoring. None of the women had organ
damage, inflammatory diseases, on estrogen replacement therapy or any other risk
factors. Participants wore an ABP monitor that both records heart rate during 24
hours and noted their awake and sleep times. HF were assessed using an everyday
complaint questionnaire that included symptoms associated with menopause. Each
participant was asked whether or not she had experienced each symptom during the
two weeks before the interview. RESULTS: Fifty-five of the participants (45%)
reported having had HF during the two weeks before they completed the
questionnaire. The results show that the prevalence of essential hypertension
(EH) in the group of women who had HF was significantly higher than the group of
women that did not have HF (p = 0.035). The authors also found that hypertensive
women had HF more often than normotensive women (p = 0.035), but other parameters
including mean awake and sleep systolic BP values, mean awake and sleep diastolic
BP values, heart rates, and nocturnal dipping of BP did not differ statistically
among the group of women who had HF and the group of women who did not have HF (p
> 0.05). CONCLUSIONS: These data suggest that the prevalence of EH in the group
of women who have HF is significantly higher than the group of women that does
not have HF.
PMID- 25134288
TI - High rates of abnormalities in hysterosalpingography in couples with male factor
infertility.
AB - The rate of anatomical abnormalities in infertile couples with obvious male
factor is unknown. For this purpose the authors retrospectively analyzed 376
hysterosalpingographies (HSG) of couples with severe male factor. Patients were
subdivided into four groups according to the woman's age, and primary or
secondary infertility: A--less than 35-years-old, primary infertility, B--less
than 35-years-old, secondary infertility, C--35-years-old or more, primary
infertility, and D--35-years-old or more, secondary infertility. Overall,
abnormalities in HSG were demonstrated in 25.5% of the patients, and in 18, 21,
52, and 40 percent of patients in groups A, B, C and D, respectively. Age was
found to be a significant independent risk factor (p < 0.05) while primary or
secondary infertility was not. The adjusted odds ratio for woman who were 35
years-old or more to have any abnormalities in HSG were 3.7-fold greater (95% CI
2.2- 6.23), than women who were less than 35-years-old. In conclusion, relatively
high rates of female mechanical abnormalities may be found even in infertile
couples with obvious male factor and are significantly more prevalent in older
women.
PMID- 25134289
TI - Frozen section of uterine curetting in excluding the possibility of ectopic
pregnancy--a clinicopathologic study of 715 cases.
AB - INTRODUCTION: To investigate the utility of frozen section of uterine curetting
in excluding the possibility of ectopic pregnancy (EP). MATERIALS AND METHODS: A
retrospective analysis of 715 curetting records in the present hospital from July
1999 to May 2009 was obtained. All specimens were processed routinely with frozen
section and paraffin section. RESULTS: Of 715 cases, frozen section analyses were
discordant in 33 cases (4.6%), including 32 cases under-diagnosed, and one case
over-diagnosed, compared with the final diagnoses. Frozen section had a
sensitivity of 92.6%, specificity of 99.6%, and frozen section accuracy rate of
95.4%. CONCLUSIONS: Frozen section is a useful and rapid method to differentiate
EP from intrauterine pregnancy.
PMID- 25134290
TI - Increased platelet count in severe peritoneal endometriosis.
AB - OBJECTIVE: Platelet count (PC) is higher in chronic inflammatory diseases. The
aim of this study was to evaluate the PC in patients with severe pelvic
endometriosis. MATERIALS AND METHODS: Patients with advanced stage pelvic
endometriosis were retrospectively evaluated in a tertiary center between January
2009 and December 2011. Patients with pelvic endometriosis were divided into two
groups; advanced stage peritoneal endometriosis were classified as Group 1 (n =
28). Group 2 consisted of 29 patients which had ovarian endometrioma without
clinically apparent peritoneal endometriosis foci. Group 3 included 51 women as
control subjects. PC between the groups was tested by Student's t test. The mean
values of three groups were analyzed by using one way ANOVA test followed post
hoc test Bonferroni. RESULTS: PC in patients with pelvic endometriosis were found
to be higher from the control group (290 +/- 67 10(9)/1; 264 +/- 63 10(9)/1,
respectively; p = 0.038). Patients with peritoneal endometriosis (Group 1) had
significantly higher PCs compared with the healthy controls (309 +/- 65 10(9)/1;
264 +/- 63 10(9)/1; respectively; p = 0.011). CONCLUSION: Increased PC in
advanced stage pelvic endometriosis may be a sign of increased systemic
inflammation. The systemic inflammation may be more apparent in advanced stage
peritoneal endometriosis.
PMID- 25134291
TI - Risk of recurrent menorrhagia after hydrothermoablation: role of GnRH analogues
neoadjuvant treatment in long-term successful rate.
AB - OBJECTIVE: To evaluate the long-term effectiveness of presurgical therapy with
GnRH analogues in patients who underwenthydrothermal endometrial ablation (HTA)
for menorrhagia and assess the relationship between sonographically measured
myometrium thickness and pelvic pain. MATERIALS AND METHODS: A prospective
randomized control study comparing 15 women (Group A) with presurgical
subcutaneous triptorelin depot injection before HTA with controls (Group B, n =
15). Inclusion criteria were: recurrent menorrhagia, uterus length < 12 cm, no
previous hormonal therapy for at least six month, and family plan completed.
Student's t test was applied, as appropriate, to compare continuous variables.
Proportion were compared with chi-squared. RESULTS: After 12 months of follow-up,
Group A showed a significantly lower (0% vs 20%; p = 0.03) failure rate after
hydrothermoablation than the Group B and a generally higher successful rate at 24
and 48 months. The discomfort, evaluated with VAS, showed a mean value of 47.6 +/
15.9 +/- SD); 96.7% of women reported a mild-moderate postoperative pain. No
perioperative and late complications were recorded. CONCLUSIONS: Presurgical
treatment with GnRH analogues seems to improve long-term efficacy of HTA.
Perioperative pelvic pain seems to not be affected by myometrium thickness.
PMID- 25134292
TI - Serum levels of androgens and prostate-specific antigen in endometriosis.
AB - OBJECTIVE: The aim of the present study was to evaluate the levels of serum
androgens and prostate-specific antigen (PSA) levels in patients with
endometriosis. MATERIALS AND METHODS: Patients with Stage III/IV (advanced stage)
endometriosis were compared to controls with respect to basal serum levels of
total testosterone (T), free testosterone (fT), androstenedion (A),
dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulphate (DHEA-S), and PSA
in the early follicular phase of menstrual cycle for this prospective case
control study. RESULTS: Level of T, fT, A, DHEA, and DHEA-S were higher in
patients with endometriosis when compared to control subjects, but the difference
was not statistically significant. The mean PSA level was 0.0074 +/- 0.0120 ng/ml
in patients with endometriosis and 0.0059 +/- 0.0056 ng/ml in control group and
there was no statistically significant difference between groups (p = 0.58).
CONCLUSION: Serum basal androgens and PSA levels are higher in endometriosis
group with respect to control but the differences are not statistically
significant.
PMID- 25134293
TI - Rising cesarean section rates, a patient's perspective: experience from a high
birth rate country.
AB - PURPOSE OF INVESTIGATION: To investigate the effect of social class, education
and antenatal care on cesarian section (CS) rate and women's preference for CS.
MATERIALS AND METHODS: This is a descriptive study performed on 509 women
attending postnatal clinics in three primary care units in Ismailia governorate,
Egypt. The study performed via a structured questionnaire including questions
related to background socio-demographic data, questions related to obstetrical
history for the last pregnancy and delivery, and questions related to economic
standards. RESULTS: The study included 266 participants (52.3%) that delivered by
CS in their last delivery. CS rate was significantly higher in highly educated
women and high economic standard. Only 29 (7.7%) reported that they had preferred
CS as a method of delivery. Educational level and economic standards
significantly affected the proportion of women preferring CS as a method of
delivery (p = 0.02 and p = 0.01, respectively). In a stepwise logistic regression
model, significant factors affecting CS rate were: the method of delivery
preferred (p < 0.005) and educational level (p < 0.05). CONCLUSION: Educational
level and economic standards significantly affected women's preference towards CS
and CS rate.
PMID- 25134294
TI - Effectiveness of pericervical tourniquet by Foley catheter reducing blood loss at
abdominal myomectomy.
AB - OBJECTIVE: To evaluate effectivenes of pericervical tourniquet by Foley catheter
reducing blood loss at abdominal myomectomy. MATERIALS AND METHODS: Retrospective
chart review of 67 cases, with symptomatic myoma uteri and undertaken abdominal
myomectomy, was performed. Myomectomy was performed in Group 1 (n = 34) by Foley
catheter tourniquet around both uterin vessels and in Group 2 (n = 33) the
tourniquet was not performed. RESULTS: The average blood loss during myomectomy
was 286.4 +/- 137.5 ml for the tourniquet group and 673.8 +/- 172.3 ml for the
control group. Postoperative blood transfusion was necessary in two patients from
the control group. Technique significantly reduced the intraoperative blood loss
and postoperative hemoglobin fall in patients. No serious complications occured
on account of the tourniquet technique. CONCLUSIONS: The pericervical tourniquet
by Foley catheter is a safe and effective method for reducing blood loss during
abdominal myomectomy, although it should be evaluated in a randomized controlled
trial.
PMID- 25134295
TI - TVT-ABBREVO: efficacy and two years follow-up for the treatment of stress urinary
incontinence.
AB - PURPOSE: To assess the effectiveness of inside-out TVT-ABBREVO in the surgical
treatment of female stress urinary incontinence (SUI) with mean two-year follow
up. MATERIALS AND METHODS: Fifty-six women underwent surgery for moderate-severe
SUI. The technology used was the TVT-ABBREVO inside-out. Each woman at 12 and 24
months underwent postoperative evaluation by means of urodynamics, Q-tip test,
CST, transperineal ultrasonography, and administration of "King's Health
Questionnaire" (KHQ). RESULTS: The mean age of the women was 57.03 +/- 11.1 years
(range 42-75). Postoperative urodynamics (12 months follow-up) resulted to be
normal in 43/56 patients (76.79%), in 10/56 (17.86%) cases resulted in a
considerable improvement of the symptomatology, and only 1/56 (1.78%) case had de
novo overactive bladder (OAB), in 2/56 (3.57%) symptomatology unchanged. After
administration of the KHQ 43/56 cases (76.79%) had resolution of the
symptomatology, 10/56 cases (17.86%) improvement of the symptomatology, and no
change in 3/56 cases (5.36%). CONCLUSION: In the authors' experience, the TVT
ABBREVO resulted technically simple. The TVT-ABBREVO procedure provides high
objective and subjective long-term efficacy, a clinically meaningful improvement
in patient quality of life, and an excellent safety profile.
PMID- 25134296
TI - Is thrombin-activatable fibrinolysis inhibitor antigen (TAFIag) level significant
in recurrent miscarriage?
AB - OBJECTIVE: The aim of this study was to evaluate the plasma thrombin-tat
fibrinolysis inhibitor antigen (TAFIag) levels in women with recurrent
miscarriage (RM) and age-matched healthy parous women as controls. MATERIALS AND
METHODS: A total of 80 patients were enrolled in this study. As a study group
(group 1), the authors evaluated 49 RM patients who had two or more consecutive
abortions with unknown etiology before 12 weeks of gestation. The remaining 31
patients (group 2) were age-matched healthy parous women with no history of
miscarriage and experienced at least one live baby. RESULTS: Comparisons of blood
TAFIag levels revealed no statistically significant difference between women with
recurrent miscarriages and control group. CONCLUSIONS: The findings of the
present study indicated that TAFIag level was not associated with recurrent
miscarriages.
PMID- 25134297
TI - Experience of hysteroscopy indications and complications in 5,474 cases.
AB - OBJECTIVE: To evaluate the indications, intraoperative diagnoses, and
complication rates of both diagnostic and operative hysteroscopic procedures.
MATERIALS AND METHODS: Five thousand four hundred seventy-four (5474)
hysteroscopic procedures performed in the department of gynecologic endoscopy
unit between May 2005 and December 2012 were retrospectively analyzed from the
archives. Indications, intraoperative diagnosis, and complications of all
gynecological endoscopic procedures are recorded. RESULTS: Abnormal uterine
bleeding in premenopausal and postmenopausal women was the most frequent
indication for diagnostic hysteroscopies in 1,887 (40%) cases. The most common
preoperative indication for operative hysteroscopy was endometrial polyps in 469
(55.7%) cases and submucous leiomyomas in 151 (17.9%) cases. In this series, the
most common complication was uterine perforation which occured in 15 (0.27%) out
of 5,474 cases and the rate for diagnostic hysteroscopy and operative
hysteroscopy was 0.06% and 1%, respectively. CONCLUSION: Hysteroscopy is a safe
and effective minimally invasive procedure with very low complication rate.
PMID- 25134298
TI - Effects of natural progesterone on endometriosis in an experimental rat model: is
it effective?
AB - To assess the effects of the natural progesterone on the endometriosis in a rat
model. MATERIALS AND METHODS: Endometriosis was surgically induced in 20 rats by
transplanting an autologous fragment of endometrial tissue onto the inner surface
of the abdominal wall. Rats in control group had no medication but 2.5
mg/kg/weekly natural progesterone was administered to rats in study group for
four weeks. After that, all rats were sacrificed and dimensions of endometriosis
were measured and they were evaluated morphologically and histologically. Scoring
systems were used to evaluate preservation of epithelia. RESULTS: Two rats in the
study group and one rat in the control group died of complications related to
surgery. At the end of the treatment, there was a reduction in the size of the
endometriotic lesions in the study group (p < 0.01). According to histological
evaluation, the study group had lower score than control goup which was
statistically significant (p = 0.014). CONCLUSIONS: Natural progesterone is
effective against endometriosis in rat model.
PMID- 25134299
TI - Marked improvement of the autoimmune syndrome associated with autoimmune
hepatitis by treatment with sympathomimetic amines.
AB - PURPOSE: To evaluate the effect of sympathomimetic amine therapy for a life
threatening autoimmune disorder. MATERIALS AND METHODS: Dextroamphetamine sulfate
was used to treat edema, myalgia, and chronic fatigue associated with autoimmune
hepatitis (AIH). RESULTS: Sympathomimetic amine therapy completely abrogated the
symptoms associated with AIH. CONCLUSIONS: AIH should be added to the long list
of chronic treatment-refractory conditions that respond quickly and effectively
to treatment with sympathomimetic amines.
PMID- 25134300
TI - Abdominal intrauterine vacuum aspiration.
AB - Evaluating and "cleaning" of the uterine cavity is probably the most performed
operation in women. It is done for several reasons: abortion, evaluation of
irregular bleeding in premenopausal period, and postmenopausal bleeding. Abortion
is undoubtedly the number one procedure with more than 44 million pregnancies
terminated every year. This procedure should not be underestimated and a careful
preoperative evaluation is needed. Ideally a sensitive pregnancy test should be
done together with an ultrasound in order to confirm a uterine pregnancy,
excluding extra-uterine pregnancy, and to detect genital and/or uterine
malformations. Three out of four abortions are performed by surgical methods.
Surgical methods include a sharp, blunt, and suction curettage. Suction curettage
or vacuum aspiration is the preferred method. Despite the fact that it is a
relative safe procedure with major complications in less than one percent of
cases, it is still responsible for 13% of all maternal deaths. All the figures
have not declined in the last decade. Trauma, perforation, and bleeding are a
danger triage. When there is a perforation, a laparoscopy should be performed
immediately, in order to detect intra-abdominal lacerations and bleeding. The
bleeding should be stopped as soon as possible in order to not destabilize the
patient. When there is a perforation in the uterus, this "entrance" can be used
to perform the curettage. This is particularly useful if there is trauma of the
isthmus and uterine wall, and it is difficult to identify the uterine canal. A
curettage is a frequent performed procedure, which should not be underestimated.
If there is a perforation in the uterus, then this opening can safely be used for
vacuum aspiration.
PMID- 25134301
TI - Salmonella ovarian abscess in a patient with rheumatoid arthritis (RA): a case
report with literature review.
AB - Salmonella ovarian abscess in a patient with rheumatoid arthritis (RA) is
reported here. A 33-year-old nulliparous woman with a 16-year history of RA who
had been treated with corticosteroid and immunosuppressive drugs was diagnosed as
having a non-typhoidal Salmonella ovarian abscess which might have been preceded
by an occurrence of endometriotic cyst. Multidisciplinary therapy including
surgical intervention was required to complete the eradication of infection.
Although Salmonella ovarian abscess is rare, it may cause a serious complication
in the ovary harboring endometriotic cyst through sustained presence of
Salmonella bacteraemia.
PMID- 25134302
TI - Transient sixth cranial nerve palsy following orgasm abrogated by treatment with
sympathomimetic amines.
AB - PURPOSE: To describe a unique disorder where a transient 6th nerve palsy leading
to diploplia following orgasm developed in a 28-year-old woman. This coincided
with a weight gain of 100 pounds in a short time without a corresponding change
in dietary habits. MATERIALS AND METHODS: She was treated with the
sympathomimetic amine dextroamphetamine sulfate. RESULTS: Indeed she immediately
responded to treatment with dextroamphetamine sulfate sustained release capsules
with complete resolution of the episodes of 6th nerve palsy following orgasm.
CONCLUSIONS: The main importance of this case is that it suggests that orgasm
causes a transient generalized decrease in sympathetic nervous system activity
and that the achievement of an orgasm may require an increase in the sympathetic
nervous system activity.
PMID- 25134303
TI - Normal evolution of pregnancy complicated by a giant placental chorioangioma.
AB - Placental chorioangioma is a benign vascular tumour of placental origin. Here The
authors report a case of a pregnant patient who presented placental chorioangioma
measuring 11 cm in the greatest diameter at 37 weeks at term and in labor.
PMID- 25134304
TI - Failure to improve a thin endometrium in the late proliferative phase with
uterine infusion of granulocyte-colony stimulating factor.
AB - PURPOSE: To determine if the treatment with uterine infusion of granulocyte
colony-stimulating factor (G-CSF) can improve endometrial thickness in an
infertile woman with a double uterus, who consistently showed a thin endometrium
in the late proliferative phase either in controlled ovarian hyperstimulation
(COH) IVF-ET cycles or with graduated estrogen/sildenafil protocols for frozen
embryo transfer (ET). MATERIALS AND METHODS: A single uterine infusion of G-CSF
was performed in the late proliferative phase in a woman who only attained a five
mm thickness despite a high dose vaginal and oral estradiol regimen plus
sildenafil. RESULTS: No increase was found within a couple days. CONCLUSIONS: A
previous four-case study in another center found 100% improvement in the
endometrial thickness in women with consistently thin endometria. Perhaps the
uterine anomaly in the present case prevented the response of the endometrium.
PMID- 25134305
TI - Uterine inversion after controlled cord traction during caesarean section: a case
report.
AB - INTRODUCTION: Inversion of the uterus during caesarean section is a rare but life
threatening complication of the procedure that requires immediate treatment,
which is reversion and awareness due to the very serious adverse effects that it
may have. MATERIALS AND METHODS: The authors present a case of a 34-year-old para
1 woman of Greek ethnicity who underwent a scheduled caesarean section at 39
weeks of gestation. During the procedure, a uterine inversion occurred as a
controlled cord traction was applied in order to achieve placental detachment,
after the delivery of the baby. It was managed by immediate manual uterine
reversion, which was performed after exteriorization of the uterus. There were no
adverse effects. CONCLUSION: Uterine inversion during caesarean section is a
serious complication, but fortunately very rare. However, the obstetrician should
be aware that the complication should be quickly identified and act without
hesitation because it is critical for the well being of the patient.
PMID- 25134306
TI - Sympathomimetic amine therapy found effective for treatment of refractory chronic
complex regional pain syndrome (reflex sympathetic dystrophy).
AB - PURPOSE: To determine if treatment with sympathomimetic amines could improve the
pain from complex regional pain disorder (CRPD) which was keeping a woman from
trying to conceive her second child. MATERIALS AND METHODS: Dextroamphetamine
sulfate was prescribed. RESULTS: Within a short length of time the woman's wrist
pain considerably improved to the point that she is ready to try in vitro
fertilization once again to have a second baby. CONCLUSIONS: Though
sympathomimetic amines are used by some reproductive endocrinologists for
unexplained infertility and unexplained recurrent miscarriages, the most common
use by the gynecologist is for pelvic pain. Despite the thought by some
clinicians and researchers that the etiology for CRPD may be related to
sympathetic nervous system hyperactivity (and thus sympathomimetic amines could
theoretically exacerbate the symptoms), in fact, the treatment with
dextroamphetamine sulfate may turn out to be a new and possibly the most
effective, least risky, and least expensive treatment to date for CRPD.
PMID- 25134307
TI - Pallister-Killian syndrome in a preterm newborn who died soon after precipitous
delivery: cytogenetic analysis.
AB - The authors report a preterm neonate with dysmorphic traits and cleft palate who
was born preterm because of precipitous delivery and died soon after birth
notwithstanding neonatal intensive care unit (NICU) support. The cytogenetic
analysis on fibroblasts from post-mortem skin biopsy demonstrated a Pallister
Killian syndrome (PKS). PKS is a cytogenetically syndrome characterized by a
tissue limited mosaic distribution of one isochromosome 12p (tetrasomy 12p).
Clinical manifestations of PKS are variable, and some symptoms may overlap with
other malformative syndromes, thus the correct diagnosis mainly depends on the
demonstration of the specific cytogenetic abnormality.
PMID- 25134309
TI - Cutaneous reactions to bed bug bites.
PMID- 25134308
TI - Spontaneous cutaneous umbilical endometriosis: a rare variant of extragenital
endometriosis.
AB - Umbilical endometriosis is a very uncommon condition which presents as a
pigmented umbilical nodule, papular or cystic, with symptoms punctuated rhythmed
by menses. The authors report the case of a 32-year-old with spontaneous
umbilical endometriosis. Surgical resection was performed with a good cosmetic
result and no recurrence at six months. A review of the literature allowed the
authors to discuss the diagnosis difficulties and treatment in a underdeveloped
country.
PMID- 25134310
TI - Low-level laser/light therapy for androgenetic alopecia.
AB - Androgenetic alopecia (AGA) is a persistent and pervasive condition that affects
men worldwide. Some common treatment options for AGA include hair prosthetics,
oral and topical medications, and surgical hair restoration (SHR). Pharmaceutical
and SHR treatments are associated with limitations including adverse side effects
and significant financial burden. Low-level laser or light (LLL) devices offer
alternative treatment options that are not typically associated with adverse side
effects or significant costs. There are clinic- and home-based LLL devices. One
home-based laser comb device has set a standard for others; however, this device
requires time devoted to carefully moving the comb through the hair to allow
laser penetration to the scalp. A novel helmet-like LLL device for hair growth
has proven effective in preliminary trials and allows for hands-free use.
Regardless, there are few clinical trials that have been conducted regarding LLL
devices for AGA and results are mixed. Further research is required to establish
the true efficacy of these devices for hair growth in comparison to existing
alternative therapies.
PMID- 25134311
TI - Motives for cosmetic procedures in Saudi women.
AB - The media-fuelled obsession with beauty in modern society has led more women to
seek elective cosmetic procedures to meet the portrayed ideals of beauty in
different cultures. This study gives insights into incentives and desires to
undergo cosmetic procedures in a conservative society with strict religious
practices where women are veiled. Questionnaire data were obtained from 509 Saudi
women who responded to a survey distributed randomly to a sample of Saudi women
aged 17 to 72 years. At least 1 elective cosmetic procedure was performed in 42%
of the women, of whom 77.8% wore a veil. Another 33% considered having a
procedure. The motives for seeking a cosmetic procedure were to improve self
esteem in 83.7%, attract a husband in 63.3%, or prevent a husband from seeking
another wife in 36.2%. The decision to seek a procedure was affected by the
media, with high peer influence. Motivation for elective cosmetic procedures in
Saudi women is influenced by a combination of emotional and cultural factors,
level of education, marital status, and religious beliefs. The veil is not an
impediment for seeking such procedures. The limitation of the study was missing
data analysis as some items in the questionnaire were completed inaccurately or
left unanswered.
PMID- 25134313
TI - Cutaneous malignancies in immunosuppressed organ transplant recipients.
AB - During the past century, organ transplantation has delivered the miracle of life
to more than 500,000 patients in need. Secondary malignancies have developed as
an unforeseen consequence of intense immunosuppressive regimens. Cutaneous
malignancies have been recognized as the most frequent cancer that arises post
transplantation. Among organ transplant recipients (OTRs), skin cancer is a
substantial cause of morbidity and potential mortality. The authors discuss
epidemiology and clinical presentation of cutaneous malignancies; associated risk
factors; recommendation for the care of immunosuppressed OTRs, and emerging
therapies on the horizon.
PMID- 25134312
TI - A high glycerol-containing leave-on scalp care treatment to improve dandruff.
AB - Dandruff is a common cosmetic condition associated with flaky scalp skin and
pruritus. It is generally treated with regular use of antifungal-based shampoos.
Research into factors underlying the characteristic skin lesions has revealed
perturbations in epidermal differentiation and a dramatic deterioration in the
associated process of stratum corneum (SC) maturation. These observations suggest
that directly addressing the quality of the SC could have a scalp benefit. In
this study, the authors investigated the efficacy of a moisturising leave-on
lotion (LOL) containing a high concentration of glycerol (10%) and other known
skin benefit agents (saturated fatty acid and sunflower seed oil) to reduce
dandruff over an 8-week treatment period with 3 applications per week. Results of
expert visual grading and biophysical measurements of SC parameters
(transepidermal water loss and hydration) revealed a significant reduction in the
dandruffcondition over this period, with significant improvement in both SC water
barrier function and hydration. These scalp skin benefits were maintained for up
to a week following cessation of the treatment. This study indicates that use of
a glycerol-rich substantive LOL, designed to directly improve the quality of the
SC barrier can have a significant impact on the dandruff condition.
PMID- 25134314
TI - Basal cell carcinoma: pathophysiology.
AB - Basal cell carcinoma (BCC) is the most common skin cancer in humans, which
typically appears over the sun-exposed skin as a slow-growing, locally invasive
lesion that rarely metastasizes. Although the exact etiology of BCC is unknown,
there exists a well-established relationship between BCC and the pilo-sebaceous
unit, and it is currently thought to originate from pluri-potential cells in the
basal layer of the epidermis or the follicle. The patched/hedgehog intracellular
signaling pathway plays a central role in both sporadic BCCs and nevoid BCC
syndrome (Gorlin syndrome). This pathway is vital for the regulation of cell
growth, and differentiation and loss of inhibition of this pathway is associated
with development of BCC. The sonic hedgehog protein is the most relevant to BCC;
nevertheless, the Patched (PTCH) protein is the ligand-binding component of the
hedgehog receptor complex in the cell membrane. The other protein member of the
receptor complex, smoothened (SMO), is responsible for transducing hedgehog
signaling to downstream genes, leading to abnormal cell proliferation. The
importance of this pathway is highlighted by the successful use in advanced forms
of BCC of vismodegib, a Food and Drug Administration-approved drug, that
selectively inhibits SMO. The UV-specific nucleotide changes in the tumor
suppressor genes, TP53 and PTCH, have also been implicated in the development of
BCC.
PMID- 25134315
TI - New wine in old bottles: the coming deluge of aggressive cutaneous cancers and
precancers.
PMID- 25134316
TI - Hot topics in the cosmetics industry.
PMID- 25134317
TI - Kafka and the enigmatic case of cutaneous myiasis.
PMID- 25134318
TI - A rare case of aplasia cutis with vanishing twin syndrome and unusual
presentation.
PMID- 25134319
TI - The challenge of managing increasingly complex cancer toxicity.
PMID- 25134320
TI - It's time to have 'the talk': cost communication and patient-centered care.
PMID- 25134321
TI - Cardiovascular toxicity of biologic agents for cancer therapy.
AB - There has been significant progress in the development of new anticancer
therapies over the last decade.Targeted therapies, including anti-human epidermal
growth factor receptor 2 agents, vascular endothelial growth factor inhibitors,
and tyrosine kinase inhibitors, have been important components of current
treatment strategies. However, many of these therapies have been associated with
chemotherapy-related cardiac dysfunction. While newer targeted agents provide "on
target" anticancer activity, their "off-target" drug effects encompass a wide
range of cardiovascular toxicities. Many of these toxicities are reversible, but
they may limit the use and length of treatment and compromise its efficacy.
Oncologists are often the first to diagnose chemotherapy-related cardiac
dysfunction, although patients with advanced cardiotoxicity are referred to
cardiologists for further care. The field of cardio-oncology has emerged as a
necessary discipline to address these disabling complications. In order to
prevent late-stage cardiotoxicity, an early collaborative effort between
oncologists and cardiologists is warranted to risk-stratify patients prior to
therapy and to treat at the earliest signs of cardiotoxicity. It is therefore of
utmost importance for oncologists to be aware of the cardiotoxicities of
anticancer therapies, and to be familiar with modifiable risk factors and early
interventions that can prevent long-term cardiac damage.
PMID- 25134322
TI - Cardiotoxicity of targeted agents in oncology: a medical oncology perspective.
PMID- 25134323
TI - Cardiovascular toxicity of Newer chemotherapeutic agents: the heart of the
matter.
PMID- 25134324
TI - Salvage chemotherapy for refractory germ cell tumors.
PMID- 25134325
TI - Esophagogastric junction and gastric adenocarcinoma: neoadjuvant and adjuvant
therapy, and future directions.
AB - In North America, gastric cancer is the third most common gastrointestinal
malignancy and the third most lethal neoplasm overall. In Asia, gastric cancer
represents an even more serious problem: in Japan, it is the most common cancer
in men. The standard primary therapy for gastric cancer is surgical resection; in
esophagogastric-junction (EGJ) adenocarcinoma, which is often included in studies
of gastric cancer, surgery is also typically the initial management strategy.
However, the rates of locoregional and distant recurrence following surgery with
curative intent have remained high. Investigators have explored a variety of ways
of reducing these rates and improving survival in patients with gastric and EGJ
cancers. These strategies have included explorations of the optimal extent of
regional lymphadenectomy at the time of gastric resection; investigation of
different neoadjuvant, perioperative, and adjuvant chemotherapy regimens; use of
preoperative and postoperative radiation therapy; and the use of pre- and
postoperative chemoradiotherapy (CRT).To date, benefit has been seen in gastric
cancer patients with the use of what is called a"D2 resection"(which includes
lymph nodes of stations 7 through 12) and with adjuvant CRT (in the West) or
adjuvant chemotherapy with S-1 (in Japan); and neoadjuvant CRT has been shown to
have a survival benefit in patients with EGJ cancers.
PMID- 25134326
TI - EGJ and esophageal cancers: choosing induction therapy so as to err on the side
of overtreatment rather than undertreatment when staging is imperfect.
PMID- 25134327
TI - Esophagogastric junction and gastric adenocarcinoma: current challenges and
future directions.
PMID- 25134328
TI - The role of radical prostatectomy and lymph node dissection in the treatment of
young men with high-grade node-positive prostate cancer: there may be no RCTs-but
there are good reasons to include surgery.
PMID- 25134329
TI - The role of radical prostatectomy and lymph node dissection in the treatment of
young men with high-grade node-positive prostate cancer: less is more--the
benefits of surgery do not yet outweigh potential harms.
PMID- 25134330
TI - Double trouble: a case of concurrent de novo T790M and L858R EGFR mutations in
treatment-naive advanced non-small-cell lung cancer.
PMID- 25134331
TI - My love-hate relationship with hospitals.
PMID- 25134332
TI - Survivorship is not a passive sport.
PMID- 25134333
TI - Hypofractionation for breast cancer: lessons learned from our neighbors to the
north and across the pond.
AB - Adjuvant whole breast irradiation was established within the standard of care for
breast-conserving therapy in the early 1980s, following the results of major
randomized trials comparing mastectomy vs breast-conserving surgery and
radiation. Since that time, techniques and treatment strategies have evolved, but
one major thread that carries forward is the need to balance cost, efficacy,
complications, and convenience. Fortunately, data from randomized trials
conducted in Canada and Great Britain provide a solid framework for the
consideration of hypofractionated radiation in the treatment of breast cancer. In
this review we discuss the rationale and underlying radiobiologic concepts for
hypofractionation, and review the clinical trials and American Society for
Radiation Oncology (ASTRO) guidelines supporting this approach. We also review
the practical considerations for treatment planning, including dosimetric
criteria and how to approach treatment of the node-positive patient. In the
current era of healthcare reform and cost awareness, thoughtful utilization of
hypofractionation may offer considerable savings to individual patients and the
healthcare system--without compromising clinical outcomes or quality of life.
PMID- 25134334
TI - Fractionation in breast cancer radiotherapy for conservative treatment: are we
really done learning?
PMID- 25134335
TI - Consider a single intraoperative fraction for patients eligible for
hypofractionated regimens?
PMID- 25134336
TI - Distribution and heterogeneity of heterochromatin in the European huchen (Hucho
hucho Linnaeus, 1758) (Salmonidae).
AB - The chromosomal characteristics, locations and variations of the heterochromatin
were studied in the European huchen (Hucho hucho, Linnaeus, 1758) karyotype using
conventional C- banding, endonuclease digestion banding, silver nitrate (AgNO3),
chromomycin A3 (CMA3) and DAPI staining techniques. The karyotype consists of 82
chromosomes: 13 pairs of metacentric chromosomes, 2 pairs of submetacentric
chromosomes and 26 pairs of subtelo-acrocentric chromosomes (NF = 112). Original
data on the chromosomal distribution of segments resistant to Alu I, Dde I and
Mbo I restriction endonucleases and identification of the C-banded
heterochromatin presented here have been used to characterize the huchen
karyotype. On the basis of the banding patterns provided in the course of
restriction enzyme digestion, AgNO3/CMA3 staining and C-banding we distinguished
twelve types of heterochromatin grouped in four areas of the European huchen
chromosomes. One pair of NOR-bearing chromosomes was found to be polymorphic in
size and displayed two distinct forms. A combination of various staining
techniques provided original data concerning heterochromatin distribution and
heterogeneity in the European huchen which enabled better karyotypic definition
of this fish species.
PMID- 25134337
TI - Molecular variability of the COI fragment supports the systematic position of
Enarmoniini within the subfamily Olethreutinae (Lepidoptera: Tortricidae).
AB - The Tortricidae, a globally distributed family of Lepidoptera, consists of
approximately 10,000 described species, of which a large number do not have
clearly defined taxonomic positions. In the present paper the systematics of
Enarmoniini based on molecular data is compared to systematics based on
morphology. Two genera of Enarmoniini were used for analysis: the type-genus
Enarmonia (one species examined) and Ancylis (7 species examined). A comparison
of a 606 bp homologous fragment of the COI mitochondrial gene revealed that
Enarmoniini form a cluster distinct from Olethreutini (3 genera and 7 species
examined), Eucosmini (2 genera, 4 species) and Grapholitini (4 genera, 9
species). In our opinion the molecular studies combined with previously obtained
morphological data should facilitate a more natural classification system of this
relatively poorly explored family of Microlepidoptera. Altogether, 30 species of
Tortricidae were examined.
PMID- 25134338
TI - Estimation of global content of 5-methylcytosine in DNA during allantoic and
pulmonary respiration in the chicken embryo.
AB - DNA methylation is an epigenetic modification that plays an important role in the
proper development and functioning of an organism. The DNA methylation level is
species-, tissue- and organelle-specific, and the methylation pattern is
determined during embryogenesis. A correlation between methylation and age is
also observed. Epigenetic phenomena are an enormously interesting research
subject, not only from the perspective of pure science, but also due to their
possible applications in medicine. The aim of this study was to determine the
global DNA methylation level in relation to the developmental stage of the
embryo. The global level of 5-methylcytosine in the DNA during pulmonary
respiration was found to be higher than during allantoic respiration. The
analysis shows a clear dependence between the stage of individual development and
the global DNA level of 5-methylcytosine. In the future, methylation level may be
a determinant of age and perhaps even a tool for predicting life expectancy.
Abnormalities in the methylation process result in premature ageing at the
cellular and individual level.
PMID- 25134339
TI - The fatty acid profile of muscle tissue of ram lambs with diverse genotypes.
AB - The aim of the study was to determine the fatty acid profile of intramuscular fat
for genetically diverse sheep breeds kept in the same environmental and feeding
conditions. The study was conducted on 30 (15 in each breed) wrzosowka and
zelaznenska ram lambs slaughtered at 23-25 kg of life weight. The meat samples
for analysis were taken from longissimus lumborum muscle. The meat of wrzosowka
ram lambs contained almost twofold less (P < or = 0.01) intramuscular fat
compared to zelaznenska sheep. Lower (P < or = 0.05) total of SFA and higher (P <
or = 0.05) MUFA content in muscle tissue of wrzos6wka sheep was shown. The
predominant monounsaturated acid was oleic acid which amounted to almost 90% of
all MUFA. The activity of enzyme Delta9 desaturase evidenced by the higher values
of C14:1/C14:0, C18:1/Cl8:0 (P < or = 0.01) and C16:1/C16:0 (P < or = 0.05)
indices was also recorded for wrzos6wka ram lambs. The UFA/SFA (P < or = 0.05)
and MUFA/SFA (P < or = 0.05) ratios as well as the value of the trombogenic index
(TI) (P < or = 0.05) were more favourable in muscle tissue for wrzos6wka than
zelaznenska rams lambs. Therefore, the meat from leaner animals is more
beneficial for human health.
PMID- 25134340
TI - Reproductive performance of New Zealand White rabbits after depletion of
apoptotic spermatozoa.
AB - The objective of this study was to assess the utility of the magnetic-activated
cell sorting (MACS) technique used for improving characteristics and quality of
insemination doses by the elimination ofapoptotic rabbit spermatozoa from a
heterospermic pool (Experiment 1) as well as from the ejaculates of individual
bucks (Experiment 2). Superparamagnetic microbeads conjugated with annexin V
eliminated spermatozoa with externalized phosphatidylserine via MACS. The control
(untreated) and magnetically separated spermatozoa (in both E1 and E2) were used
for artificial insemination of hormonally treated rabbit does. MACS separation of
spermatozoa yielded two fractions: annexin V-negative (AnV) and annexin V
positive (AnV+). The CASA analysis after MACS sperm sorting revealed that the
proportion of apoptotic spermatozoa in the semen of New Zealand White bucks
varied from 7 to 20%. Transmission electron microscopy revealed that MACS
treatment might eliminate spermatozoa with membrane damages and released
acrosomal matter. However, the MACS separation (in both E1 and E2) did not affect
the reproductive parameters of rabbit does.
PMID- 25134341
TI - The effect of mammary gland-specific transgene expression on rabbit reproductive
gland structure.
AB - Transgenic rabbits are excellent animal models for human diseases and suitable
bioreactors for the production of recombinant proteins on an experimental and
commercial scale. The aim of this study was to compare the structure of the mWAP
hFVIII transgenic and non-transgenic rabbit ovarian and testicular tissue.
Ovarian and testicular tissue samples were taken from transgenic and non
transgenic New Zealand White rabbits, examined by optical microscopy and analyzed
morphometrically. An increase of the relative volume of primary follicles and a
decrease of the relative volume of antral follicles was detected in the
transgenic ovarian structure (P < 0.05), but other developmental follicular
stages and follicular diameters were not affected (P > 0.05). In the testes a
significant decrease (P < 0.05) of the epithelial height was detected in the
transgenic testicular structure, but the relative volume of all basic structures
(germinal epithelium, interstitium and lumen) was unaltered (P > 0.05).
Generally, this study demonstrates a weak negative effect of mWAP-hFVIII
transgenesis on rabbit gonadal structure.
PMID- 25134342
TI - The effect of different fat sources in the diet on the composition of adipose
tissue in arctic foxes (Alopex lagopus L.).
AB - The study investigated the effect of vegetable and animal fat in the feed ration
on the fatty acid profile of reserve fat in the arctic fox. Varying proportions
of saturated and unsaturated fats in the feed ration comprised the experimental
factor. In order to differentiate contents of saturated and unsaturated fatty
acids in the experimental feed rations, various percentages of rapeseed oil and
turkey fat were applied. The subcutaneous and circum-organal fat in this study
differed considerably in terms of contents of individual fatty acids and between
individual groups of acids. The circum-organal fat contained much higher amounts
of unsaturated acids, but at the same time it was characterized by a lower amount
of monounsaturated acids. Significant differences were also found in the contents
of as many as 11 fatty acids. Recorded results indicate a potential modification
of reserve fat in the arctic fox, a model representative of carnivorous animals
(Carnivora). The possibility of the partial substitution of animal fat with
vegetable oil (rape oil) in the nutritive diet of artic foxes was confirmed.
PMID- 25134343
TI - Sexual maturation in common vole (Microtus arvalis) males raised under laboratory
conditions.
AB - The common vole is one ofthe most numerous rodents in Europe and Asia but its
reproductive biology is not fully described. It is thought that females reach
reproductive abilities at a very young age, however, there is no data concerning
male sexual maturation. The aim of the present study was to determine the rate of
sexual maturation of males of the common vole. Research was carried out on 4, 6,
8 and 10 week-old animals. Body, testes and accessory sex glands weights were
compared to evaluate morphological development. Epididymal sperm quality was
assessed by a motility test, sperm tail membrane integrity, viability, maturity
and sperm head morphology. Moreover, the number of sperm cells in 1 mm3 of semen
was evaluated. The largest body weights were observed in 8 and 10 week-old males,
which also possessed the highest relative weights of gonads and accessory sex
glands. These groups of males produce about 2 times more gametes than 6 week-old
individuals. The highest seamen quality was noted in 8 and 10 week-old males.
Based on the obtained results, it is concluded that among the investigated age
groups the most appropriate male age for fertile copulation is between 8 and 10
weeks.
PMID- 25134344
TI - Are chondroclasts and osteoclasts identical?
AB - Brief characteristics of cells termed "osteoclasts" and "chondroclasts" are
outlined and reasons to consider them as the same cell type, able to resorb
calcified matrix, are discussed.
PMID- 25134345
TI - The effect of saprotrophic fungi on the development and hatching of Fasciola
hepatica eggs.
AB - The aim of this study was to determine the effect of 6 common soil fungi species:
Alternaria alternata (Fr.) Keissl., Aspergillus candidus Link, Penicillium
chrysogenum Thom, P. commune Thom, Trichothecium roseum (Pers.) Link and
Ulocladium sp., on the hatching of miracidia, i.e., free living larvae of liver
fluke (Fasciola hepatica). To this end, the eggs of F. hepatica were incubated in
water in the presence of one of the aforementioned fungi species and in tap water
(control) at a temperature of 26 degrees C. At the 15th day of incubation we
determined the number of nonembryonated, embryonated and hatched eggs. We
observed different degrees of antagonistic influences by the tested fungal
strains on the development of F. hepatica eggs. Among the examined fungi, the
strongest ovistatic effects were exhibited by Trichothecium roseum, Penicillium
chrysogenum (R-3) and P. commune. The study showed no morphological damage to the
shells of the F. hepatica eggs which may suggest a biochemical basis of
antagonistic interactions by the fungi associated with the activity of fungal
enzymes, mycotoxins and antibiotics. Low or no activity of peptide hydrolases in
Penicillium chrysogenum and P. commune in the API ZYM test suggests their
insignificant role in the degradation of shell proteins ofF. hepatica eggs.
PMID- 25134346
TI - Effects of anesthetic compounds on responses of earthworms to electrostimulation.
AB - Earthworms play an important role in biomedical research, and some surgical
procedures require anesthesia. Anesthetic treatments used so far usually induce
convulsive body movements connected with extrusion of coelomocyte-containing
coelomic fluid that may affect experimental results. Extensive movements
connected with the expulsion of coelomic fluid are exploited by immunologists as
a method of harvesting immunocompetent coelomocytes from worms subjected to mild
electrostimulation (4.5V). The aim of the investigations was to find anesthetic
drugs without unintentional coelomocyte depletion. Experiments were performed on
adult specimens of Dendrobaena veneta, the coelomocytes of which consist of
amoebocytes and riboflavin-storing eleocytes. Earthworm mobility was filmed and
extrusion of coelomocytes was quantified by detection of eleocyte-derived
riboflavin in immersion fluid. Treatments included earthworms (1) immersed either
in physiological saline (controls) or in a solution of one of the tested
anesthetic drugs; (2) electrostimulated immediately after anesthesia, and (3)
electrostimulated a second time after a 1-hour recovery period. The well
established fish and amphibian anesthetic agent MS-222 induced coelomocyte
expulsion. In contrast, solutions of the mammalian local anesthetic drug,
prilocaine hydrochloride (0.25-0.5%, 5-10 min) caused temporal earthworm
immobilization followed by recovery, thus showing utility as an efficient
earthworm anesthetic.
PMID- 25134348
TI - [Butterflies].
PMID- 25134347
TI - [In memory of Prof Lech Dzialoszynski (1912-2014) ].
PMID- 25134349
TI - [Aging and longevity].
AB - During the last three centuries the expected lifespan in civilized countries has
increased several times. The fastest growing groups are seniors (65+) and
centenarians. Increased lifespan results in postponing of aging and age-related
diseases. On the other hand, an increase in the number of people suffering from
age-related diseases can be observed. Studies concerning longevity and aging help
to elucidate the mechanisms responsible for these processes and give hope for
finding the recipe for a healthy and long lifespan. Aging and longevity are
modulated by genetic, epigenetic and stochastic factors. Already some variants of
genes which correlate with longevity are known. Products of these genes are
involved in lipid metabolism and in nutrient sensing signaling pathways such as:
insulin/IGF-1 and TOR. Good indicators for human polymorphism study are results
obtained using model organisms such as S. cerevisiae, C. elegans, D. melanogaster
and laboratory mice. Aging and longevity are evolutionary conserved. Evolutionary
theories concerning aging can be divided into two general categories: programmed
and non-programmed ones. According to programmed theories aging is adaptive and
can lead to altruistic death of kins. Non-programmed theories predict that
organisms only have a limited amount of energy that has to be divided between
reproductive activities and the maintenance of the non-reproductive aspects of
the organism. Aging is the effect of natural degrading processes that result in
the accumulation of damage. Accumulation of damaged DNA and proteins can lead to
cellular senescence, inflammaging and age-related diseases. Strategies for
postponing aging mainly rely on protecting and/or eliminating these lesions.
PMID- 25134350
TI - [Markers of cellular senescence].
AB - Cellular senescence is a complex process associated with irreversible cell cycle
arrest. We can distinguish replicative senescence, which is telomere dependent
and stress-induced premature senescence (SIPS), which is telomere independent.
Replicative senescence can be observed in culture after a few weeks or months,
depending on the cell type. On the other hand SIPS can be observed a few days
after treating with a senescence inducing agent. Till now a universal marker of
senescence has not been decribed. Studies concerning senescence are possible
thanks to the existance of many markers of senescence which enable to observe
molecular as well as biochemical changes associated with this process. The
presence of a few markers of senescence allows us to be sure that cells underwent
senescence.
PMID- 25134351
TI - [Impact of cellular senescence on organismal aging and age-related diseases].
AB - Development of the civilization and medicine enables an even longer lifespan of
people. To modulate the aging process it is necessary to discover its molecular
mechanism and its causes. It has been known for almost 60 years that cells
undergo senescence. A lot of markers of senescence have been described to
distinguish senescent cells. Every year we can observe an increase in the number
of data, supporting the thesis that the reason for aging of the whole organism is
cellular senescence. We age because cells building tissues and organs undergo
senescence. It is also believed that cellular senescence can increase the
frequency of age-related diseases. The role of cellular senescence strictly
depends on the age of the individual. In young ones it is essential for:
protection against cancer and tissue regeneration. In old ones it causes tissues
and organs dysfunctions and leads to age-related diseases. Slowing down aging
could prevent age-related diseases and this seems to be more promising than
curing them. To enrich our knowledge concerning aging it is important to
understand signaling pathways leading to senescence. Recently a new role of
cellular senescence has been discovered, namely during embryogenesis. This
observation is very surprising and shows a new face of cellular senescence. It is
possible that, similarly to the previously described role of apoptosis in
embryogenesis, senescence is indispensable for proper organogenesis. Cellular
senescence seems to be the universal and fundamental process, the role of which
changes during the lifespan.
PMID- 25134352
TI - [Stem cells and senescence].
AB - Stem cells are undifferentiated cells that can differentiate into specialized
cells, that build the whole body. These rare cells are required for homeostasis
and tissue replacement throughout the human lifespan, and appear to be
characterized by a few specific physiological and biochemical properties,
particularly the capacity for self-renewal. Recent studies suggest that stem
cells may undergo senescence, what plays a crucial role in organismal aging.
Importantly, both senescence and apoptosis are anti-cancer mechanisms that
counteract neoplastic transformation of stem cells. On the other hand, mechanisms
that suppress the development of cancer may also induce an unwanted consequence:
a decline in the number and functional alterations of stem cells with advancing
age. These functional changes reflect harmful effects of age on the genome,
epigenome, and proteome of stem cells. Some of which arise cell independently and
others which are imposed by an age-related change in the local milieu or systemic
environment. Remarkably, some of the changes, particularly epigenomic and
proteomic ones, are potentially reversible, and both environmental (e.g. caloric
restrictions, hypoxia) and genetic interventions can lead to inducible
pluripotency. Here, we discuss recent discoveries in the field of senescence of
stem cells. These findings have profound implications, not only for our
understanding of stem cells' biology and organismal aging, but also for stem cell
based regenerative medicine and stem cell-based therapy of age-related diseases.
PMID- 25134353
TI - [Neuronal ageing].
AB - Ageing leads to irreversible alterations in the nervous system, which to various
extent impair its functions such as capacity to learn and memory. In old neurons
and brain, similarly to what may take place in other cells, there is increased
oxidative stress, disturbed energetic homeostasis and metabolism, accumulation of
damage in proteins and nucleic acids. Characteristic of old neurons are
alterations in plasticity, synaptic transmission, sensitivity to neurotrophic
factors and cytoskeletal changes. Some markers of senescence, whose one of them
is SA-beta-galactosidase were used to show the process of neuronal ageing both in
vitro, and in vivo. Some research suggest that, despite the fact that neurons are
postmitotic cells, it is cell cycle proteins which play a certain role in their
biology, e.g. differentiation. However, their role in neuronal ageing is not
known or explained. Ageing is the serious factor of development of
neurodegenerative diseases among others Alzheimer disease.
PMID- 25134354
TI - [Senescence of mesothelial cells].
AB - The mesothelium is a specific group of cells having characteristics of both
mesenchymal and epithelial cells. One of the most unique properties of these
cells is a low proliferative capacity and a small number of achievable division.
The purpose of this paper was to present the current state of knowledge on the
causes of premature senescence of peritoneal mesothelial cells and to discuss the
molecular events involved in this process. Particular attention was paid to the
role of telomeres, the activity of senescence effectors at the level of the cell
cycle, and the action of oxidative stress and transforming growth factor beta1.
Moreover, the relationship between senescence of mesothelial cells and the aging
of the organism as a whole, as well as the participation of senescent cells in
the development of the intraperitoneal cancer metastasis was addressed.
PMID- 25134355
TI - [The role of cellular senescence in carcinogenesis and antitumor therapy].
AB - Cellular senescence is the process that lead to terminal growth arrest induced by
unrepairable double strand DNA damage (DSB). Moreover, activation of the
oncogenes as well as inhibition of the tumor suppressor genes were shown to
contribute to senescence induction and the senescent cells were identified in the
premalignant lesions. Thus senescence is considered as an natural antitumor
barrier that act at the early stages of cancerogenesis to stop the proliferation
of transformed cells. Interestingly, the premalignant cells that escaped
senescence and progress into full blown tumor cells still remain sensitive to
induction of senescence, for example during chemio- or radiotherapy. Thus,
induction of cancer cell senescence, similarly to apoptosis, is considered to
restrain tumor growth and thus contribute to effectiveness of anticancer therapy.
The senescent cells, although do not proliferate, remain viable and metabolically
active. They secret a lot of cytokines, mitogens as well as enzymes degrading
extracellular matrix. These factors can have opposing effect on neighboring
cells, leading to senescence induction or stimulation of proliferation. Thus,
senescence can act as an double edge sword that inhibit the propagation of
potentially dangerous, transformed cells on one hand or induce cell division of
the same cell on the other. Presently a lot of work is focused on finding new
therapeutic strategies that would involve the tumor targeted senescence induction
in both early late stages of cancer development. Nevertheless, the unwanted
influence of the senescent cells on the microenvironment, requires careful
monitoring the effects of pro-senescent therapies in each case.
PMID- 25134356
TI - [Natural compounds--modulators of senescence and cell death].
AB - For hundreds of years natural compounds have been used in herbal medicine. They
have been known for their antibacterial, antifungal, anticancer activities as
well as for enhancing wound healing and improving immunity. Recently growing
interest in natural compounds has been observed, due to their ability to modulate
cellular senescence. Particularly interesting are these compounds that can induce
tumor senescence, delay senescence of normal cells or reverse changes associated
with senescence - acting as "rejuvenation" agents. It has been shown that some of
the natural compounds can both promote senescence of tumor cells as well as
prevent it in normal cells. Thus, they can be useful in therapy of age-related
diseases. Natural compounds can regulate nutrient and energy sensing signaling
pathways that are involved in senescence. They can also influence the synthesis
of reactive oxygen species, secretion of cytokines, telomere shortening or
epigenetic changes of DNA. Natural agents often act in a pleiotropic manner. They
can modulate cellular senescence in many ways e.g. by direct neutralization of
free radicals and affecting other regulatory signaling pathways. Furthermore
natural compounds, commonly used for years e.g. as spices, usually don't have any
side effects. Therefore their use as dietary supplements or in long term therapy
appears to be relatively safe.
PMID- 25134357
TI - [Immunological theory of senescence].
AB - Senescence can result from decreased potential of the immune system to respond to
foreign and self antigens. The most common effect is the inhibition to destroy
dying and cancer cells and the decrease of the immune response to pathogens.
Aging is closely related to inflammatory phenotype, which facilitate the
development of age-related diseases. The mammal immune system is highly organized
and adapted to react to a wide range of antigens. According to the immunological
theory, the causative agents of senescence are multilevel changes of development
and functions of immune cells. Some of changes can be beneficial for the
maintenance of homeostasis and lifespan in continuously changing endogenous
environment and immune history of the organism.
PMID- 25134358
TI - [Mechanisms of the immune system ageing and some age-associated diseases].
AB - In this paper the concept of homeostenosis (progressive reduction of ability to
adapt producing loss of effectiveness) of the immune system is presented as a
cause of the system ageing. In particular, the progression of immune system
homeostenosis was shown to be associated with previous or ongoing chronic
inflammatory diseases, including rheumatoid arthritis, type 2 diabetes, chronic
kidney disease and Alzheimer's disease.
PMID- 25134359
TI - [The role of reactive oxygen species and mitochondria in aging].
AB - Aging is a biological phenomenon concerning all living multicellular organisms.
Many studies have been conducted to identify the mechanisms underlying this
process. To date, multiple theories have been proposed to explain the causes of
aging. One of them is the free radical theory which postulates that reactive
oxygen species (ROS), extremely reactive chemical molecules, are the major cause
of the aging process. These free radicals are mainly produced by the
mitochondrial respiratory chain as a result of electron transport and the
reduction of the oxygen molecule. Toxic effects of ROS on cellular components
lead to accumulation of oxidative damage which causes cellular dysfunction with
age. The free radical theory has been one of the most popular theories of aging
for many years. Scientific research on different model organisms aiming to verify
the theory has produced abundant data, supporting the theory or, on the contrary,
suggesting strong evidence against it. At present, the free radical theory of
aging is no longer considered to be true.
PMID- 25134360
TI - [The role of the DNA damage response in apoptosis and cell senescence].
AB - The genetic material is constantly subjected to DNA damage which is caused by
physiological processes occuring in the cell and is exposed to exogenous DNA
damaging agents. Eucariotic cells have developed a system called the DNA damage
response (DDR), which is responsible for maintaining genomic inegrity. DNA damage
can lead to senescence, DNA repair as well as to cell death. The key protein in
the DDR pathway is p53. This protein undergoes numerous posttranslational
modifications and can be involved in the activation of many genes and proteins
leading to survival or cell death. In cell senescence the p53 protein leads to
the induction of p21, which causes cell cycle arrest. In apoptosis p53
participates in the activation of caspases, which are responsible for the
degradation of many proteins.
PMID- 25134361
TI - Correction of bone and softtissue deformity of the single implant in the
aesthetic zone: a case treated with alveolar ridge preservation, modified roll
technique and a digitally coded healing abutment.
AB - The correction of soft tissue deformity and aesthetic rehabilitation of a single
implant in the aesthetic zone with a combination of periodontal and prosthodontic
approaches is described. Soft tissue deformity was corrected resulting in
significant soft tissue volume increase and eliminated the need for prosthetic
gingival replacement. A two stage implant placement protocol, ridge preservation
and a soft tissue augmentation flap design preserved epithelium attachment to the
connective tissues. Use of a digitally coded healing abutment preserved the newly
established soft tissue volume, allowed impression making without implant
component removal, and minimized trauma to the newly established soft tissue
architecture.
PMID- 25134362
TI - Colour stability of acrylic resin denture teeth after immersion in different
beverages.
AB - The colour stability of acrylic resin denture teeth in beverages was
investigated. A spectrophotometer measured the colour (CIE-L*a*b* system) of all
specimens after storage in distilled water/for 24 h at 37 degrees C (T0).
Specimens were then immersed in various beverages. After 15 days (T1) and 30 days
(T2), for each material, the mean deltaE values were calculated and compared by
two-way ANOVA and Tukey intervals (alpha = 0.05). In the deltaT0T1 period,
specimens stored in red wine were significantly discoloured, compared to
distilled water (P = 0.003). There was no difference between immersion solutions
in deltaET0T2 (P = 0.772) and in deltaET1T2 (P = 0.058), and no difference
between materials in all immersion periods.
PMID- 25134363
TI - A hinged two-part partial denture used in conjunction with severely tilted teeth:
a case report.
AB - A two-part sectional denture can be a useful treatment option when the presence
of severe hard tissue undercuts compromises the provision of a satisfactory
conventional prosthesis. This article presents a case report illustrating the
effective use of a hinged two-part denture in restoring a mandibular Kennedy
Class IV edentulous area. A sectional denture approach was selected because of
severe proximal and lingual undercuts.
PMID- 25134365
TI - BSSPD Annual Conference. Apex Hotel, Dundee 14th - 15th April 2014.
PMID- 25134364
TI - One-year clinical evaluation of a Glass Carbomer fissure sealant, a preliminary
study.
AB - Glass Carbomer is a new generation of restorative material developed from glass
ionomer cements with possibility of gradual mineralization into fluorapatite. The
aim of this clinical trial was to investigate the retention of Glass Carbomer
fissure sealant after 12 months, in comparison to a commonly used conventional
resin-based sealant. Forty-eight teeth in 24 patients [mean (SD) = 8 (2.3) years]
with well-delineated fissure morphology were randomly divided into two equal
groups and sealed with Bis-GMA resin-based Helioseal F (group A, Ivoclar
Vivadent, Liechtenstein) and Glass Carbomer (group B, Glass Carbomer Sealant,
Glass Carbomer Products, Leiden, Netherlands) using the split mouth design.
Materials were placed and set according to the manufacturer's instructions using
a polymerization unit Bluephase 16i (Vivadent, Liechtenstein). Complete sealant
retentions in both groups were 100% and 75% after 6 and 12 months of clinical
service, respectively. There were there were no secondary caries lesions in both
groups after 6 months; two new carious lesions were detected in both groups after
12 months. The Mann-Whitney U test revealed no significant difference between the
two groups at both evaluations points (P > 0.05). Glass Carbomer material showed
a similar retention rate when compared with a resin-based sealant. Future studies
are required to examine the long-term performance of Glass Carbomer sealants.
PMID- 25134366
TI - Effect of preoxidation on the bond strength of titanium and porcelain.
AB - The purpose of this study was to investigate the effect of preoxidation on
porcelain titanium- bond strength and the effect of paste bonder (adhesive) on
the titanium porcelain bond strength. 11 specimens of commercially pure titanium
(26 x 7 x 3 mm) were prepared by different heat treatments in programmable dental
furnace. Identification of the oxides formed on the metal surface was conducted
with an X-Ray diffractometer with CuKalpha radiation. Vickers hardness numbers
were determine. Additional 50 specimens of commercially pure titanium were used
to bond with low fusing porcelain. The bond strength was measured in a universal
testing machine. X-ray diffraction analysis of the surface of pure titanium
revealed that the relative peak intensity of alpha -Ti decreased and that of TiO2
increased with increasing firing temperature. The Vickers hardness number
decreased initially as the temperature increased but it increased remarkably
above 900 degrees C & was harder in air than vacuum. The tensile shear bond
strength was highest in the green stage i.e. without preoxidation of metal, and
decreased above 900 degrees C, and was the lowest in the group without paste
bonder application. The difference in bond strengths was statistically highly
significant for all groups. Preoxidation under vacuum before porcelain firing can
effectively improve bonding. The adhesive provided with the low fusing porcelain
helps in the bond between titanium & porcelain.
PMID- 25134367
TI - Colour matching of composite resin cements with their corresponding try-in
pastes.
AB - Two shades of four resin cements (Calibra, Clearfil Esthetic, Insure, Variolink
II), in light- and dual-curing modes, were tested for colour matching with their
corresponding try-in pastes, immediately after photopolymerization and after 24
hour dry and dark storage. Colour measurements were performed for 0.8 mm-thick
specimens through a 0.8mm-thick ceramic plate. For each resin cement, colour
differences (deltaE) were calculated between the two curing modes, and between
the corresponding try-in paste, at baseline and after 24h. deltaE>0 values were
detected between all resin cements and their try-in pastes, which were
brand/shade/curing mode depended. The try-in pastes of the Variolink II system
demonstrated the best colour matching (deltaE<2). Try-in pastes of Calibra and
Insure, at both curing modes, did not match at an acceptable value, the shade of
their corresponding resin cements (deltaE>3.3). Calibra presented the highest
colour differences. deltaE values of the Clearfil Esthetic system immediately
after photo-activation ranged between 2 and 3 units. A ceramic restoration may
fail aesthetically as a result of not acceptable colour match (deltaE>3.3)
between the shade of certain resin cements and their relevant try-in pastes.
PMID- 25134368
TI - Evaluation of Cerec endocrowns: a preliminary cohort study.
AB - This study aimed to evaluate clinical qualities and evolution on ceramic
endocrowns produced with the Cerec 3D (Sirona). Endocrowns were produced in a
hospital environment and evaluated according to the FDI criteria on the day of
placement and 6 months afterwards. Each item was graded from 1 (good) to 5 (bad).
A global score, as well as a score for aesthetics, functioning and biological
integration was assessed for each evaluation. During the 6-month evaluation
period, the scores were always related to good clinical quality, except for
single crown restoration. The scores did not change between the two periods of
evaluation.
PMID- 25134369
TI - The pharmaceutical symbolism of O. Henry.
PMID- 25134370
TI - Deja Vu--the recycling of penicillin in post-liberation Paris.
PMID- 25134371
TI - Confessions of a quasi-collector/archivist: the UCSF Robert L. Day Collection.
PMID- 25134372
TI - The dispensatory of the United States of America, (2nd edition, 1834) by George
B. Wood and Franklin Bache.
PMID- 25134373
TI - Mahadeva Lal Schroff: father of Indian pharmacy education.
PMID- 25134374
TI - Evaluation of multiplex real time polymerase chain reaction and procalcitonin in
the diagnosis of sepsis.
AB - BACKGROUND: Sepsis is one of the most serious and life-threatening clinical
conditions of childhood. This study has been designed to evaluate how useful
multiplex real-time polymerase chain reaction (PCR) is in the early diagnosis of
responsible microorganisms of sepsis and to specify how serial procalcitonin
level measurement is helpful to support diagnosis of sepsis. METHODS: A total of
79 blood samples from 69 consecutive patients were collected for this prospective
study between 01 Sept 2009 - 29 Feb 2012. RESULTS: In the evaluation of patients
who are diagnosed with sepsis out of 69 patients with 79 clinical sepsis, 24
(30.37%) had positive blood culture and 19 (24%) samples were positive for PCR.
When blood culture and multiplex real-time PCR results were compared, multiplex
real-time PCR had a sensitivity of 75% and specificity of 100%. When the 2
microorganisms that multiplex real-time PCR cannot detect are excluded
sensitivity increased to 81.8% and specificity did not differ. Procalcitonin
levels on the day sepsis is suspected had a mean level of 13.91 ng/mL (+/-
49.26), on the 1st day (after 24 hours) the mean level of procalcitonin was 15.05
ng/mL (+/- 43.95), on the 2nd day (after 48 hours) it was 14.89 ng/mL (+/-
41.57). Mean procalcitonin levels of 50 children admitted with complaints other
than infection and systemic inflammation was 0.06 ng/mL (+/- 0.04). CONCLUSIONS:
In conclusion, multiplex real-time PCR test would be useful in the early
diagnosis of sepsis. Studying procalcitonin levels is helpful in the early
diagnosis of sepsis but does not have any correlation with the isolation of
microorganisms in blood culture and survival.
PMID- 25134375
TI - Indirect estimation of reference intervals for thyroid parameters.
AB - BACKGROUND: The aim of this work was to determine indirect reference intervals
from patients' results obtained during routine laboratory work. This could be an
accurate alternative to the laborious and expensive job of producing reference
intervals for populations according to international recommendations. METHODS:
All the results for thyrotropin (TSH), total and free thyroxine, and
triiodothyronine (T4, fT4, T3, and fT3) stored in our laboratory information
system between 2008 and 2011 were included in this study. We used logarithmic
transformation of the raw data to exclude outliers. After visual observation of
the data distribution, we estimated non-parametric reference intervals. A
standard normal deviation test was performed to test the significance of
differences between subgroups. RESULTS: There was no significant difference in
the serum levels of the analyzed thyroid parameters, so we calculated combined
reference values. However, we found a significant difference in TSH values
between ambulatory and hospitalized patients, but only in 2011. Indirect
reference values for TSH, T4, fT4, T3 and fT3 were 0.42 - 3.67 mIU/L, 66.0 -
136.10 nmol/L, 10.20 - 18.40 pmol/L, 1.10 - 2.39 nmol/L, and 3.17 - 5.59 pmol/L,
respectively. CONCLUSIONS: The indirect determination of laboratory-specific
reference intervals using patients' laboratory data is a relatively easy and
inexpensive method. Also, indirect reference limits will be more precise and true
if skewness and kurtosis of the distribution are not too large.
PMID- 25134377
TI - Hemoglobin Q-Thailand and its combinations with other forms of thalassemia or
hemoglobinopathies in northern Thailand.
AB - BACKGROUND: There have been no reports for the frequency of Hb Q-Thailand [alpha
74(EF3)Asp --> His, GAC > CAC] and its combinations either with other forms of
thalassemia or hemoglobinopathies in Northern Thailand. The aims of this study
were to search for Hb Q-Thailand and its combinations in Northern Thai population
and to analyze fractions of hemoglobin in Hb Q-Thailand and its combinations on
high performance liquid chromatography (HPLC) chromatograms and/or capillary
electrophoresis (CE) electrophoregrams. METHODS: Blood samples from public and
private hospitals in 7 northern provinces of Thailand were analyzed for
thalassemia and hemoglobinopathy diagnoses using HPLC and/or CE and DNA analysis
techniques at the Thalassemia Laboratory, Associated Medical Sciences Clinical
Service Center, Chiang Mai, Thailand. RESULTS: Hb Q-Thailand was found in 13 of
13,596 (0.10%) samples; 6 were heterozygous Hb Q-Thailand, 4 were compound Hb Q
Thailand/alpha-thalassemia-1 Southeast Asian (SEA) type deletion and 3 with
combinations of Hb Q-Thailand/beta(0)-thalassemia, Hb Q-Thailand/Hb E and Hb Q
Thailand/Hb E/alpha-thalassemia-1 SEA type deletion. The fractions of hemoglobin
on HPLC chromatograms and CE electrophoregrams were observed based on types of
combinations. CONCLUSIONS: Hb Q-Thailand and its combinations could be found in
northern Thai population with the frequency of 0.10%. Thus, the better
understanding of HPLC chromatogram and/or CE electrophoregram patterns of Hb Q
Thailand and its combination is essential for diagnosis and genetic counseling of
thalassemia and hemoglobinopathies in this area.
PMID- 25134376
TI - The evaluation of serum surfactant protein D (SP-D) levels as a biomarker of lung
injury in tuberculosis and different lung diseases.
AB - BACKGROUND: To evaluate the predictive powers of serum surfactant protein D (SP
D) levels as a biomarker of lung damage in tuberculosis and lung diseases.
METHODS: This study prospectively included 137 subjects who applied to our
hospital. We measured serum SP-D levels from patients with active tuberculosis
(TB) (n = 35), chronic obstructive disease (COPD) patients experiencing acute
exacerbations (n = 30), patients with pneumonia (n = 45), and control subjects (n
= 27). RESULTS: The mean age of all patients was 54.89 +/- 18.81 years (15 to 100
years); males accounted for two-thirds (70.1%) of the cases. Serum SP-D levels
were higher in patients with pnemonia, tuberculosis, and COPD than in control
patients (p < 0.001, p < 0.001, and p < 0.001, respectively). Serum SP-D levels
in patients with pneumonia, tuberculosis, and COPD were higher than in the
control group and mean serum SP-D levels were associated with pulmonary injury
scores in patients with pneumonia, severity of COPD attack, and the extent of
radiological lung involvement in patients with pneumonia and TB. CONCLUSIONS:
Serum SP-D may be a useful biomarker of the severity of pneumonia, COPD, and
tuberculosis.
PMID- 25134378
TI - Serum procalcitonin in cirrhotic patients with septic shock: relationship with
adrenal insufficiency and clinical outcomes.
AB - BACKGROUND: Serum procalcitonin is commonly used to differentiate systemic
inflammation due to infection from non-infectious causes. Limited data exist on
the value of procalcitonin in predicting relative adrenal insufficiency (RAI).
This study evaluated the value of procalcitonin in predicting RAI and mortality
in cirrhotic patients with septic shock. METHODS: This was a post-hoc analysis of
a randomized placebo-controlled trial that evaluated low-dose hydrocortisone in
cirrhotic patients with septic shock. Extracted first study-day data included
serum procalcitonin, baseline serum cortisol, cortisol level after 250 microg -
adrenocorticotropic hormone stimulation test and 28 - day mortality. RAI was
defined as a baseline serum cortisol < 10 microg/dL or cortisol not rising by > 9
microg/dL after stimulation. Procalcitonin > 0.5 ng/mL was considered high.
RESULTS: Forty-five patients had serum procalcitonin measured (mean = 2.7 +/- 3.2
ng/mL, first and third quartiles were 0.3 and 3.3 ng/mL, respectively). Most
(78%) patients had high procalcitonin levels. RAI was present in 34 (76%)
patients. Patients with high procalcitonin were more likely to have RAI (odds
ratio, 4.8; 95% confidence interval, 1.1 - 22.1). Receiver operator
characteristic curve analysis showed that the best cut-off for detecting RAI was
1.0 ng/mL (sensitivity = 79% and specificity = 55%). High serum procalcitonin was
not associated with 28 -day mortality (80% for normal procalcitonin and 77% for
high procalcitonin, p = 0.61). CONCLUSIONS: High serum procalcitonin was highly
associated with RAI in cirrhotic patients with septic shock. Procalcitonin was
not associated with 28 - day mortality in this patient population.
PMID- 25134379
TI - Biochemical evaluation of hyaluronic acid in breast cancer.
AB - BACKGROUND: The latest experimental studies on human cancer diseases have
observed the bioactive role of hyaluronic acid (HA) during carcinogenesis. HA is
a component of the extra-cellular matrix (ECM). It is closely correlated with
tumor cell growth, proliferation, and metastasis. The present study aimed to
evaluate the biochemical role of HA and its degrading enzymes and products in
breast cancer (BC) patients under therapy treatment. METHODS: An ELISA method was
used to determine HA levels and standard spectrophotometric techniques were used
to estimate the activities of HA degrading enzymes hyaluronidase (HAS), N-acetyl
beta-D-glucosminidase (NAG), and beta-glucuronidase (beta-Glu) and the
concentration of both glucoseamine (G-Amine) and glucuronic acid (GA) as
degrading products in blood sera of 50 BC patients before and after chemotherapy
treatment and in blood sera of 40 healthy women as controls. Statistical analyses
were performed by a statistical package for social sciences (SPSS, version 15.0).
RESULTS: Elevated serum HA levels, increased HAS, NAG, and beta-Glu activities
and high concentrations of G-Amine and GA were significantly found (p < 0.001) in
patients before treatment compared to controls. After all BC patients had
received the first chemotherapy course, HA and its previous degrading parameters
were significantly decreased (p < 0.001) in post-treated patients compared to pre
treated patients. CONCLUSIONS: Hyaluronic acid and its degrading enzymes and
products can be considered a biomarker for early detection of recurrent disease
and also for monitoring the effective therapeutic follow up of BC patients.
PMID- 25134381
TI - The endothelial protective effects of pioglitazone on insulin resistance in
endothelial cells.
AB - BACKGROUND: Insulin resistance plays an important role in vascular endothelial
damage and atherosclerosis. Pioglitazone is an insulin-sensitizing agent and can
reduce insulin resistance. METHODS: In this study, the cellular model of insulin
resistance was used to investigate the mechanisms involved in the endothelial
protective effects of pioglitazone in a vascular endothelial cell damage model.
RESULTS: The results showed that pioglitazone could effectively increase the
survival rate of human umbilical vein endothelial cells (ECV), reduce apoptosis,
and relieve insulin resistance damage. To understand the endothelial protective
effect mechanisms of pioglitazone, we showed that 50 ng/mL and 100 ng/mL of
pioglitazone could upregulate the levels of inducible nitric oxide synthase (NOS)
and pioglitazone could induce NO levels. CONCLUSIONS: These results suggested
that pioglitazone could have endothelial protective effects in a vascular
endothelial cell damage model of insulin resistance and used to prevent
beforehand and treat a vascular endothelial cell damage of insulin resistance.
PMID- 25134380
TI - Establishing reference values for blood urea nitrogen and serum creatinine in
Chinese Han ethnic adult men.
AB - BACKGROUND: The aim was to calculate the two-sided 95th percentile reference
values for blood urea nitrogen (BUN) and serum creatinine (SCr) in Chinese Han
ethnic adult men. METHODS: Serum samples were collected from Chinese Han ethnic
adult men aged 20 - 69 years. After screening based on the inclusion and
exclusion criteria, a total of 1575 individuals were enrolled in our study. BUN
and SCr values were measured on an automatic analyzer (Dade Behring, USA). The
data was analyzed and calculated using nonparametric statistical methods.
RESULTS: BUN and SCr values were not normally distributed. The reference values
were in the range 3.3 - 7.5 mmol/L for BUN and 64 - 113 micromol/L for SCr. BUN
levels were significantly lower in the smoking group than the non-smoking group
(Z = -4.52, p < 10(-5)). An increase with age was observed in BUN levels (r(s) =
0.172, p < 0(-5)) and lower SCr levels were weakly associated with the older
subjects (r(s) = -0.071, p = 0.005). Moreover, it was found that higher Body Mass
Index (BMI) tended toward higher levels of SCr (r(s) = 0.118, p < 10(-5)).
CONCLUSIONS: The reference values established for BUN and SCr exhibit a slight
deviation compared to those developed in previous studies. We propose reference
values of BUN for smokers and non-smokers be constructed, and age- and BMI
specific reference values be applied in clinical laboratories.
PMID- 25134382
TI - Determination of reference values for serum folate and vitamin B12 using three
different immunoassays: is it worth making an effort to produce them in our
laboratory?
AB - BACKGROUND: Despite being a widely studied concept, the reference interval is the
most widely used medical decision-making tool. As such, it is vital that these
limits are correctly established and regularly reviewed in the clinical
laboratory. METHODS: The reference population comprised 315 healthy individuals
selected a priori from Bizkaia province. Blood and serum samples were sent for
subsequent assay of vitamin B12 and folate using three immunochemical methods.
Reference values were calculated using non-parametric methods. RESULTS: The
reference values for serum vitamin B12 and folate were almost identical to those
obtained previously using the same methods. Use of new reference values led to an
increase in the kappa value despite the low agreement in the case of vitamin B12
(0.4 - 0.62). However, precision obtained for vitamin B12 (94.48 - 96.55%) and
folate (95.77 - 97.18%) was very high. The intraclass correlation coefficient
ranged from 0.723 to 0.894. Furthermore, a Passing-Bablok regression analysis
gave acceptable correlation coefficients of 0.75 - 0.94 for vitamin B12 and 0.92
0.95 for folate. CONCLUSIONS: Vitamin B12 and folate deficiencies are currently
being over-diagnosed leading to an increase in the number of unnecessary
consultations. The main conclusion that can be drawn from our study has resulted
in a change in reference values in our laboratory, with a subsequent increase in
our ability to accurately detect possible deficiencies. Furthermore, as this
study involved all methods currently in use in the Basque healthcare network, its
conclusions can be extrapolated to the whole population covered by Osakidetza,
thereby improving the rational use of healthcare funding.
PMID- 25134383
TI - Clinicopathological and prognostic significance of serum cytokine levels in
breast cancer.
AB - BACKGROUND: This study was designed to examine the serum levels of six cytokines
(IFN-gamma, TNF-alpha, IL-2, IL-4, IL-5, and IL-10) in treated and untreated
breast cancer patients and assess their clinical significance. The correlation of
the Th1/Th2 type cytokine levels and the clinicopathologic variables was further
evaluated. METHODS: Cytometric Bead Array (CBA) was used to examine the levels of
Th1 cytokines (TNF-alpha, IFN-gamma, and IL-2) and Th2 cytokines (IL-4, IL-5, and
IL-10) in serum of 36 untreated and 73 treated breast cancer patients and 51
healthy females as control. RESULTS: In the untreated group, the levels of IFN
gamma, IL-4 and IL-5 were significantly higher than in control group (p < 0.05).
IFN-gamma, IL-2, IL-5, and IL-10 levels were higher in treated group than in
untreated group (p < 0.05); IFN-gamma/IL-4 ratio of the treated group was higher
than the untreated group (p < 0.05). Meanwhile, the cytokine levels were
significantly different in different pTNM stages and lymph node involvement
groups. Survival analysis revealed that the IFN-gamma/IL-4 ratio, pTNM stage, and
lymph node involvement affected the survival of breast cancer patients. The pTNM
stage was an independent significant prognostic factor. CONCLUSIONS: Breast
cancer patients presented a Th1/Th2 imbalance and immune function disorder, which
correlated with pTNM stage and lymph node involvement. Higher IFN-gamma/IL-4
ratio predicted a favorable outcome in breast cancer patients.
PMID- 25134384
TI - Proposed guidance for carryover studies, based on elementary equivalence testing
techniques.
AB - BACKGROUND: Carryover experiments are widely used for clinical chemistry and
immunochemistry analysers to evaluate and validate carryover effects. The
experimental design is well described. However, there is no guideline on the
statistical approach on data analysis, especially if absence of carryover has to
be shown. The only reporting of carryover in ppm is not helpful because its
uncertainty is not taken into account. Furthermore, the most commonly used method
fails to demonstrate the absence of carryover. We propose a step-by-step guidance
applying a new statistical design for analysis of carryover studies based on
equivalence testing, and provide a sample based tutorial. METHODS: For
statistical analysis of carryover effects an one-sided version of equivalence
testing by comparing the difference with a predefined limit (i.e., a test of non
superiority) is used. The methodology is demonstrated by measuring total betahCG
in human serum samples with a UniCel DxI 880 analyser. RESULTS: A new statistical
approach based on equivalence testing has been developed for analysis of data
resulting from a typical experimental protocol for carryover studies. Experiments
using 8 (11) cycles of high and low concentration samples are appropriate to
validate the absence of carryover with 80% (90%) power and an alpha-level of 0,05
if no carryover is expected. We propose to predefine an acceptance criterion
based on the imprecision (here: expressed as one standard deviation) observed for
those replicates of the low concentration samples expected to be unaffected by
carryover. In the demonstration, the absence of carry-over was concluded with a
significance of p < 0.05. CONCLUSIONS: Appropriate statistical methods should be
applied when the target of a method-validation experiment is (i) absence of any
effect, (ii) non-inferiority/non-superiority or (iii) equivalence. Using the
example of carryover studies, we show that one-sided equivalence testing is the
proper model, and propose a guidance for analysis of these experiments. The
example of carryover illustrates a methodology which is also applicable for
analysis of a wide range of experimental approaches, including method comparison,
commutability and robustness.
PMID- 25134385
TI - Transforming growth factor beta 1 as a risk factor for cardiovascular diseases in
end-stage renal disease patients treated with peritoneal dialysis.
AB - BACKGROUND: The aim of the study was to evaluate the relationship between the
atherosclerotic changes in the carotid arteries expressed as common carotid
artery intima-media thickness (CCA-IMT) with Body Mass Index (BMI), serum lipid
levels, and selected inflammatory state markers in peritoneal dialysis (PD)
patients. METHODS: The study included 67 patients (31 female and 36 male) on PD
therapy for 30.4 +/- 24.2 months. Average age of the patients was 52.9 +/- 12.5
years (ranged from 19 to 75 years). The measurement of the CCA-IMT was performed
by ultrasonography evaluation. BMI was calculated using the Quetelet formula.
Serum lipid levels and hsCRP were performed using routine methods. IL-6, TGF
beta1, TNF-alpha, and hepatic growth factor (HGF) were tested with ELISA assays.
RESULTS: In univariate analysis, the strongest factor influencing CCA-IMT was age
(R = 0.54; p < 0.0001). CCA-IMT correlated positively with BMI (R = 0.39; p =
0.003). Of the inflammatory markers studied, significant correlations with CCA
IMT were shown for IL-6 (R = 0.35; p = 0.009), and TGF-beta (R = 0.31; p = 0.02).
In multiple regression, only In TGF-beta1 (partial correlation coefficient =
0.29; p = 0.04) appeared to predict CCA-IMT independently of age and BMI, while
IL-6 was not significant in the analysis. The regression model including age, BMI
and TGF-beta1 as independent variables, explained 43% of CCA-IMT variance. Again,
age was the strongest predictor of CCA-IMT (partial correlation coefficient =
0.50). CONCLUSIONS: Increased concentration of TGF-beta1 may be a biomarker of
the development of cardiovascular diseases in patients treated with PD, as well
as a prognostic factor in the evaluation of atherosclerosis progression in this
group of patients.
PMID- 25134386
TI - Genetic instability in patients with pancreatic cancer analyzed by SCARs and
electrochemical sensors.
AB - BACKGROUND: Pancreatic cancer is an aggressive disease and the fourth most common
cause of cancer death across the globe. It is often not diagnosed until it is
advanced. It is necessary to establish a new technology to detect DNA
instabilities during the progression of pancreatic cancer and to screen for new
molecular markers coupled to putative unknown oncogenes. METHODS: A total of 25
pancreatic cancer tissue specimens were analyzed by sequence-characterized
amplified regions (SCARs), including two pathological types (pancreatic ductal
adenocarcinoma and neuroendocrine carcinoma). There were 41 random primers and
eight long fragment primers used for PCR amplification, and the difference of
dNTPs consumptions were detected by nano-electrochemical sensors. Once both dATP
and dGTP are significantly different in oxidation current (reduce or increase
simultaneously), separate the different genes by electrophoresis, then clone and
sequence the genes, and carry out homology analysis. RESULTS: Both dGTP and dATP
showed good oxidation behavior on the carbon nanotube modified glassy carbon
electrode. There were 32 different fragments in malignant tissues compared with
normal control, among them a SNP located in 5'UTR of the leucine zipper protein 4
gene which is significantly correlated with pancreatic cancer (OR = 9.50) and it
was confirmed by direct sequencing. CONCLUSIONS: SCARs combined with the
nanoelectrochemical sensor can be used for screening genetic instabilities in
pancreatic cancer, and leucine zipper protein 4 was a novel pancreatic cancer
related gene.
PMID- 25134387
TI - Reference interval for osteocalcin in Chinese Han ethnic males from the
Fangchenggang Area Male Health and Examination Survey.
AB - BACKGROUND: The aim of this study was to set a reference interval (RI) for
osteocalcin (OC) in a healthy Han male population from the Fangchenggang Area
Male Health and Examination Survey (FAMHES) project and study the effects of age,
BMI, smoking, and alcohol consumption. METHODS: We used data from 2018 Han ethnic
males who participated in FAMHES project from September 2009 to December 2009.
Serum OC values were measured by electrochemiluminescence immunoassay on COBAS
6000 system E601 (Elecsys module) immunoassay analyzers. RESULTS: OC data does
not have a normal distribution or Gaussian pattern (Z = 3.791, p < 0.001). After
log-transformation, data took on a normal, Gaussian distribution (Z = 0.968, p =
0.306). The RI of serum OC was 12.49 - 43.94 ng/mL. No difference in OC
concentration was noted either between non-smoker or smoker groups (p = 0.629) or
non-drinker and drinker groups (p = 0.748). OC levels varied with age (r =
0.371, p < 0.001) and BMI (r = -0.331, p < 0.001), and the age-dependent and BMI
dependent RIs were calculated. CONCLUSIONS: The RIs for serum OC exhibit slight
differences compared to previously reported reference ranges. Age-dependent and
BMI-dependent RIs for serum OC should be implemented in clinical laboratories.
PMID- 25134388
TI - The diagnosis of high altitude illness by the determination of plasma dermcidin
isoform 2 levels by enzyme linked immunosorbent assay.
AB - BACKGROUND: High altitude illness (HAI) is a cluster of syndromes which develops
due to the injury of the central nervous system produced by the reduction of the
partial pressure of O2 in the atmosphere which disappears on decent. The HAI also
results in a prothrombotic condition leading to acute coronary syndrome (ACS),
which cannot be controlled on descent to the ground level. There is no diagnosis
in HAI to forewarn of the impending ACS. A protein identified to be dermcidin
isoform 2 (dermcidin), produced in the system due to environmental stresses, has
been reported to be a potent diabetogenic agent. Investigation was carried out to
determine the systemic stimulation of dermcidin synthesis at different levels of
altitudes in normal adult male volunteers to assess the feasibility of developing
a diagnosis for ACS in HAI due to dermcidin synthesis. METHODS: Normal,
nondiabetic, normotensive male volunteers (25 - 35 years old, n = 16)
participated in the study. The plasma dermcidin level was determined by enzyme
linked immunosorbent assay (ELISA) and by in vitro translation of dermcidin mRNA.
The plasma insulin level was determined by ELISA and blood glucose level was
determined in a glucometer (Behringer). RESULTS: The plasma dermcidin level in
the volunteers at ground level was 10 +/- 2.10 nM and increased to 80 +/- 4.62 nM
at 15000 feet altitude. For each 1000 feet increase of altitude, the dermcidin
level increased by 5.83 +/- 0.21 nM with a Coefficient of Correlation "r" =
+0.9405. The increase of plasma dermcidin level was found to be inversely related
to the decrease of plasma insulin level from 23 microunit/mL to 5 microunit/mL
from sea level to 15000 feet height ("r" = -0.9951) with concomitant increase of
blood sugar level from 80 +/- 3.6 mg/dL to 135 +/- 2.01 mg/dL. CONCLUSIONS: These
results suggest the feasibility of a diagnosis of a prediabetic condition by
determining the plasma dermcidin level in HAI by simple ELISA which may also be
useful to forewarn of the possibility of developing an impending prothrombotic
condition in HAI.
PMID- 25134389
TI - Mean platelet volume (MPV) may simply predict the severity of sepsis in preterm
infants.
AB - BACKGROUND: To evaluate the efficacy of serial mean platelet volume (MPV)
measurements in diagnosis and followup of sepsis and to compare its effectiveness
with C-reactive protein (CRP) and interleukin-6 (IL-6) in sepsis. METHODS:
Preterm infants, whose gestational age and weight were matched to each other,
were grouped as control (n = 100) and sepsis (n = 91). Platelet indices (MPV,
PDW, platelet count), CRP, and IL-6 levels were measured for the control group
and on the day of diagnosis (1st day), 3rd, and 7th days of the sepsis group.
RESULTS: There were significant differences between the control and sepsis group
in terms of platelet count and MPV/PDW levels (p < 0.05). No significant changes
were found in either platelet count or MPV and PDW of infants between early and
late onset sepsis, nor between culture proven and non proven sepsis, nor among
different infectious agents (gram positive/negative and fungal infections) (p >
0.05). Additionally, non-survivors with sepsis had higher levels of MPV and PDW
during sepsis episodes on consecutive days (p < 0.05), in contrast to lower
platelet counts in non-survivors (p < 0.05). Moreover, a positive correlation was
found between MPV and IL-6 and CRP. A MPV value of 10.35 fL was identified as the
cut off value in patients probably resulting in sepsis with a sensitivity of
97.8% and specificity of 78.7% (AUC = 0.949; p < 0.001), and a MPV value of 10.75
fL was determined as the cut off value in patients possibly resulting in death at
diagnosis with a sensitivity of 95.2% and a specificity of 84.9% (AUC = 0.944; p
< 0.001). CONCLUSIONS: The mean platelet volume can be used in addition to CRP
and IL-6 at both diagnosis and follow-up of sepsis and the response of
antimicrobial treatment.
PMID- 25134390
TI - Serum lipid profile in female patients with severe acne vulgaris.
AB - BACKGROUND: Acne vulgaris is one of the most common skin conditions affecting
young adults. The relationship between lipid profile or lipid ratios and acne is
not widely reported. METHODS: A case control study was performed in 90 females
with severe acne vulgaris. Lipid profiles were measured, lipid ratios were
calculated, and results were compared with 90 age matched healthy controls.
RESULTS: Total cholesterol, LDL-C, HDL-C, Apo A1, though, were significantly
higher in patients as compared to healthy controls but all the levels in patients
were within normal range so we calculated lipid ratios for TC/HDL, LDL/HDL,
TG/HDL, Apo B/Apo A1, Atherogenic index of plasma and found that all the ratios
were significantly higher as compared to controls using a t-test. The area under
receiver operating characteristic curve was > 0.7 for all the lipid ratios and
sensitivity and specificity were calculated for all the ratios and it was highest
for Apo A1/Apo B. CONCLUSIONS: We suggest using lipid ratios as a screening test
in females with acne vulgaris to diagnose dyslipidemia at an early stage but
further studies are required to see the effect of treating hyperlipidemia in
females with severe acne vulgaris.
PMID- 25134391
TI - Von Willebrand factor multimer structure is neither acutely nor chronically
affected by plateletpheresis.
AB - BACKGROUND: Plateletpheresis (PltPh) exposes the donor's blood to artificial
surfaces and mechanical forces such as shear stress and centrifugation. In terms
of the donor's safety and the quality of the apheresis platelet concentrate
(APC), possible impairment of platelet function due to PltPh should be excluded.
Von Willebrand factor (VWF) plays a pivotal role in platelet adhesion and
aggregation. VWF is a multimeric protein and can be damaged by adsorption or
shear stresses. It is unclear whether VWF structure could be damaged during
PltPh, leading to platelet dysfunction. METHODS: We analyzed VWF antigen
(VWF:Ag), ristocetin cofactor (VWF:RCo), and VWF multimer structure immediately
before and after apheresis in the donor and in the APC. These parameters and
factor VIII activity (FVIII:C) and closure time using PFA-100 (CT) were also
analyzed in blood samples taken from new donors before the first and before
subsequent donations and from long-term donors. RESULTS: During apheresis, VWF:Ag
falls by about 15% but the VWF multimer structure remains unchanged. In samples
taken before subsequent donations, there was a tendency of VWF:Ag and FVIII:C to
increase throughout the initial donations, but no alteration of multimer
structure. Long-term donors, however, show a normal VWF multimer structure and
normal concentrations of VWF:Ag, VWF:RCo, and FVIII:C. In some donors with low
normal VWF:Ag and VWF:RCo, PFA-100 CT was prolonged. CONCLUSIONS: VWF multimer
structure is neither acutely nor chronically affected by plateletpheresis. A
decrease in VWF:Ag with no functional damage only occurs acutely and can be
explained by the withdrawal of plasma and dilution with the anticoagulant ACD-A
due to apheresis.
PMID- 25134392
TI - Evaluation of a chromogenic medium for detection of extended-spectrum-beta
lactamase-producing Escherichia coli and Klebsiella pneumoniae strains.
AB - BACKGROUND: Because of the emergence and spread of extended-spectrum-beta
lactamase (ESBL)-producing strains which are resistant to many antibiotics,
reliable detection of ESBL is very important for infection control. Several
chromogenic media have been proposed for the detection of ESBL producers in
addition to the conventional phenotypic and genotyping methods. The aim of the
present study was to evaluate the performance of Brilliance ESBL agar (Oxoid;
Thermo Fisher Scientific, UK), a selective chromogenic agar for the detection of
ESBL-producing Escherichia coli (E. coli) and Klebsiella pneumoniae (K.
pneumoniae) strains. METHODS: A total of 237 strains (143 ESBL producers (76
isolates of E. coli and 67 isolates of K. pneumoniae) and 94 non-ESBL producers
(44 isolates of E. coli and 50 isolates of K. pneumoniae)) isolated from various
clinical specimens were included in the study. Isolates were identified by
conventional methods, Phoenix system (Becton Dickinson, USA), and mass
spectrometry. ESBL confirmation was performed by phenotypical tests. A 10 microL
aliquot of each isolate's 0.5 McFarland suspension was streaked onto Brilliance
ESBL agar. All plates were incubated at 37 degrees C for 24 hours and then were
interpreted for growth and colony color according to the manufacturer's
recommendations. Identification and ESBL test results were used to calculate the
sensitivity, specificity, positive predictive value (PPV), and negative
predictive value (NPV) of the medium evaluated at 24 hours. RESULTS: The
sensitivity, specificity, PPV, and NPV of the medium were 97.9%, 100%, 100%, and
96.9%, respectively, when considering only species specific colored colonies of
the isolates. CONCLUSIONS: Brilliance ESBL agar could provide a practical
alternative to the traditional methods for the identification of ESBL producers.
PMID- 25134393
TI - Utility of multiple-locus variant-repeat analysis method for the outbreak of the
Pseudomonas aeruginosa isolates.
AB - BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) predominated in hospitals.
METHODS: In order to determine the source of the outbreak and take effective
measures to prevent the spread, we tested their relationships between the
strains. 97 P. aeruginosa samples were analyzed by multiple-locus variable-number
tandem repeat (VNTR) analysis (MLVA) method. In order to identify a minimal
subset that could provide high discrimination, we evaluated the ability of
various VNTR sets. RESULTS: The result showed all of the 11 loci displayed high
discrimination, and the lowest loci was ms223 (h = 0.59). The 97 strains were all
discriminated (HGDI = 1.0000). The top 7-locus set produced a HGDI value of
1.0000, which was the same as the 11-locus set. The 4-locus set had a HGDI value
of 0.9972 with a clustering rate of 11.3%. The strains were divided into four
groups based on the phylogenetic clustering and genotypic characteristics. There
were obvious differences among the four groups regarding the drug-resistance
patterns of Imipenem, Ciprofloxacin, Ceftazidime, Levofloxacin, Meropenem,
Piperacillin, Cefepime, Aztreonam (p < 0.05). CONCLUSIONS: In conclusion, the
transmission of the strains was not found in this study. The 7-locus set yielded
a high discrimination, while for an easier and more robust MLVA scheme, the
number of markers can be reduced to 4 loci of ms212, ms211, ms213, and ms142.
These four strains from four inpatients in the same ward displayed the same drug
resistance spectrum. The MLVA genotype results showed the four strains had the
same gene structures. The four patients were from the same treatment group. They
showed the IMP-1 allele and belonged to the aac (6')-I type, and there was a
deletion of the OprD2 gene in four strains, supporting the MLVA results in
suggesting that they are similar.
PMID- 25134394
TI - The role of Porphyromonas gingivalis in the development of atherosclerosis and
its relationship with fim A genotype.
AB - BACKGROUND: Porphyromonas gingivalis, a major periodontal pathogen, is gaining
increasing attention for its possible association with atherosclerosis. Its
fimbriae are classified into six genotypes (Types I-V, Ib) based on the diversity
of the fim A genes encoding the fimbrial subunits. In this study, fim A
genotype's distribution of P. gingivalis was analyzed in atherosclerotic plaque
specimens. METHODS: A total of 50 atherosclerotic plaque specimens and 50 non
atherosclerotic, post stenotic aneurysm specimens were collected from patients
undergoing cardiovascular surgery. Bacterial DNA was also extracted from each
specimen, as real-time PCR was carried out with P. gingivalis-specific primer
sets. The positive specimens of P. gingivalis were further analyzed to
discriminate the fim A genotype using real-time and nested PCR methods. RESULTS:
P. gingivalis was detected only in one atherosclerotic plaque; however, the
genotype was nontypable in this specimen. CONCLUSIONS: We state that it is not
easy to show a significant relationship between P. gingivalis, its fim A
genotype, and atherosclerosis. We suggest that new extended studies based
especially upon the quantitave determination of P. gingivalis and its genotype
distribution on atherosclerotic specimens are needed to show an evident
relationship between atherosclerosis and P. gingivalis.
PMID- 25134395
TI - Masked monoclonal gammopathy in capillary electrophoresis.
AB - BACKGROUND: Although the method of choice to detect M-protein is electrophoresis
on an agarose gel, such gel electrophoresis (GE) is labor-intensive, time
consuming, and not standardized. In contrast to GE, capillary electrophoresis
(CE) has some merits because it is automated, fast, and highly reproducible.
However, CE results occasionally make the interpretation difficult and require
additional confirmatory tests like GE. METHODS: In order to assist a correct
reporting of CE results and compatible interpretations between two different
electrophoresis methods, we report here two unusual cases of monoclonal
gammopathy by a pattern of polyclonal gammopathy upon CE interpretation in
patients with end stage renal disease and multiple myeloma. RESULTS: In these
cases, serum CE showed the broad bumpy peak in the gamma region. This bumpy peak
does not drop completely flat after the reaction with anti-FLC. CONCLUSIONS:
Because the plasma cell is a B-cell lineage and plays an important role in
adaptive immunity, MG accompanying with PG is not rarely found in plasma cell
dyscrasia. If the broad bumpy peak is observed in CE, careful examinations must
be done to rule out the hidden M-peak. In our cases, a parallel use of gel-based
methods was very helpful as it revealed monoclonal bands.
PMID- 25134396
TI - Serum soluble CD200 level was higher in patients with bullous pemphigoid during
the active phase of the disease than for healthy individuals.
AB - BACKGROUND: CD200 is a novel immunosuppressive molecule, existing both as cell
membrane bound and as a soluble form in serum (sCD200), which acts to regulate
inflammatory and acquired immune responses. Recently, our study group showed that
sCD200 was found in serum and blister fluid in a patient with bullous pemphigoid
and that anti-IgE therapy impacted those levels. We therefore planned this study
to evaluate the soluble serum CD200 levels of bullous pemphigoid patients and
compare it with that of healthy controls. We also analysed the association
between the sCD200 levels and the clinical severity of the disease in bullous
pemphigoid patients. METHODS: We investigated 5 consecutive patients with bullous
pemphigoid, and 15 healthy controls were included in this study. Assessment of
clinical examination and measurement of laboratory investigation were performed
on the same day. Bullous pemphigoid patients were also assessed for Autoimmune
Bullous Skin Disorder Intensity Score (ABSIS). Concentrations of anti-BP180 and
soluble CD200 in the serum samples were quantified using ELISA kits. RESULTS: The
serum soluble CD200 level was observed to be statistically significantly higher
in patients with BP (77.6 +/- 15.7 pg/mL) compared with healthy controls (26.1 +/
6.7 pg/mL), (p < 0.001). Nevertheless, there was no statistically significant
correlation between serum soluble CD200 levels and clinical severity scores and
Anti-BP180 values (p = 0.402, p = 0.395, respectively). However, there was a
statistically significant correlation between ABSIS and Anti-BP180 levels in
patients with BP (p = 0.036). CONCLUSIONS: CD200 might play a role in the immune
response in the pathogenesis of bullous pemphigoid. However, we do not know the
exact mechanism of CD200 in the disease initiation and/or progression.
PMID- 25134397
TI - Patients infected with avian influenza A H7N9 virus have abnormally low thyroid
hormone levels.
AB - BACKGROUND: In March 2013, the novel avian influenza A H7N9 virus spread
throughout China. This study evaluated whether thyroid function was altered in
patients infected with H7N9 virus. METHODS: We analyzed thyroid-stimulating
hormone (TSH), total triiodothyronine (TT3), total tetraiodothyronine (TT4), free
triiodothyronine (FT3), and free tetraiodothyronine (FT4) levels in 17 patients
infected with H7N9 on admission to our hospital and compared the values to the
reference ranges for these thyroid hormones. RESULTS: Of the 17 patients, 12
(70.6%) patients had abnormally low TT3 levels, 10 (58.8%) patients had
abnormally low FT3 and TSH levels, and 5 (29.4%) patients had abnormally low TT4
and FT4 levels (below the lower limit of the reference ranges for each hormone).
CONCLUSIONS: Abnormally low thyroid hormone levels was common in patients
infected with H7N9.
PMID- 25134398
TI - Free light chain levels in pediatric patients with inflammatory conditions.
AB - BACKGROUND: Because free light chain assays measure polyclonal as well as
monoclonal free light chain components, some previous studies focused on the
potential utility of the free light chain assay for detecting chronic immune
stimulation, which occurs in autoimmune diseases and allergies. However, most of
these trials have been limited to adult patients. In this study, we evaluated the
paired serum and urinary free light chain levels of pediatric patients with
various inflammatory conditions to investigate the clinical significance of free
light chain measurement in pediatrics. METHODS: The study included 227 paired
serum and urine specimens from 134 pediatric patients at our hospital between
January and February of 2012. Serum and urinary FLC levels were measured using a
Freelight Kit (The Binding Site, Ltd., Birmingham, UK). RESULTS: The serum lambda
and urine kappa and lambda components were significantly increased only in the
renal impairment group, not in the mild inflammatory group. FLC ratios were not
significantly different among these groups. CONCLUSIONS: In serum, only the L
components were significantly increased. This result may indicate the presence of
a dimeric L structure, in contrast with monomeric K. FLC levels might also be
influenced by renal conditions other than mild inflammation. Therefore, as shown
in previous studies of adult patients, renal reference ranges might be needed to
interpret FLC results, especially for dimeric L components.
PMID- 25134400
TI - Auto-enroll rule may avert Obamacare turmoil in November.
PMID- 25134401
TI - High court ruling forcing NLRB to reopen cases has hospitals wary.
PMID- 25134402
TI - Hospitals Houston's energy boom fuels hospital rush to burbs.
PMID- 25134403
TI - Health spending shrinks, may surge next year.
PMID- 25134404
TI - Community health centers face major funding loss.
PMID- 25134405
TI - HFMA homes in on 'dollars and sense' consumer era.
PMID- 25134406
TI - EHR leaders vying for $11 B military contract.
PMID- 25134407
TI - CME shelter. Sunshine Act waiver for med ed payments may prompt marketing shift
for product makers.
PMID- 25134408
TI - Warning label limbo. FDA rule letting generic-drug makers update risk alerts
draws heavy flak.
PMID- 25134409
TI - Insuring against the future.
PMID- 25134410
TI - Collaboration, not vertical integration, offers best chance for success.
PMID- 25134411
TI - Doctors should be captain of the ship.
PMID- 25134412
TI - Improving women's health with no guarantee of getting paid.
PMID- 25134413
TI - New lipophilic polyelectrolyte gels containing quaternary ammonium salt with
superabsorbent capacity for organic solvents.
AB - Water and soil pollution by organic pollutants from petrochemical plants has
become one of the major environmental problems in recent years. Lipophilic
polyelectrolyte gels with ionic groups dissociable in nonpolar organic solvents
show an enhanced swelling ability in a corresponding media attributed to the
electrostatic repulsion and osmotic pressure provided by dissociated ionic
groups. Here, we synthesized new lipophilic polyelectrolyte gels based on an
easily available electrolyte monomer, methacryloxyethyl dimethyloctane ammonium
trifluoromethanesulfonimide (MODAT), and a lipophilic neutral monomer, dodecyl
acrylate by radiation-induced polymerization and cross-linking. The resultant
lipophilic polyelectrolyte gels could absorb plenty of organic solvents with
dielectric constants lower than 20 and exhibited a high absorbing ability at a
wide range of temperatures (0-40 degrees C). The maximum swelling degree could
reach as high as 200 g/g in some media, such as 1,2-dichloroethane (199.4 g/g)
and dichloromethane (204 g/g), which was much higher than that of the nonionic
gel without the addition of MODAT. Moreover, the resultant lipophilic
polyelectrolyte gels could release most of the absorbed solvents within several
hours and then be reused. It is expected that this new type of lipophilic
polyelectrolyte gels may be a suitable candidate as organic pollutant absorbents.
PMID- 25134414
TI - Assessing the quality of care in a new nation: South Sudan's first national
health facility assessment.
AB - OBJECTIVES: We adapted a rapid quality of care monitoring method to a fragile
state with two aims: to assess the delivery of child health services in South
Sudan at the time of independence and to strengthen local capacity to perform
regular rapid health facility assessments. METHODS: Using a two-stage lot quality
assurance sampling (LQAS) design, we conducted a national cross-sectional survey
among 156 randomly selected health facilities in 10 states. In each of these
facilities, we obtained information on a range of access, input, process and
performance indicators during structured interviews and observations. RESULTS:
Quality of care was poor with all states failing to achieve the 80% target for 14
of 19 indicators. For example, only 12% of facilities were classified as
acceptable for their adequate utilisation by the population for sick-child
consultations, 16% for staffing, 3% for having infection control supplies
available and 0% for having all child care guidelines. Health worker performance
was categorised as acceptable in only 6% of cases related to sick-child
assessments, 38% related to medical treatment for the given diagnosis and 33%
related to patient counselling on how to administer the prescribed drugs. Best
performance was recorded for availability of in-service training and supervision,
for seven and ten states, respectively. CONCLUSIONS: Despite ongoing instability,
the Ministry of Health developed capacity to use LQAS for measuring quality of
care nationally and state-by-state, which will support efficient and equitable
resource allocation. Overall, our data revealed a desperate need for improving
the quality of care in all states.
PMID- 25134415
TI - Retrospective cohort study of 4591 Straumann implants in private practice
setting, with up to 10-year follow-up. Part 1: multivariate survival analysis.
AB - OBJECTIVE: The purpose of this retrospective, noninterventional, open cohort
study is to report on the long-term survival of dental implants, in private
practice representing the daily realities of implant treatment. The data are
analyzed to discern statistical relationships between explanatory variables and
implant failure. MATERIALS AND METHODS: A total of 4591 Straumann implants were
placed in 2060 patients between 1999 and 2012. Patients were evaluated after 2-3
months, 1, 3, 5, and 7 years and, in some cases, up to 10 years. The cumulative
survival rate (CSR) was calculated according to the life table method and
illustrated with Kaplan-Meier survival curves. Univariate analysis was performed
to investigate the association between study variables and time to implant
failure. Variables with P -value < 0.15 were further selected for a multivariate
analysis. Statistical methods which take into account the fact that some patients
have more than one implant (therefore, dependency between implants within mouth)
had been applied. RESULTS: At the implant level, the cumulative survival rates at
3, 5, and 7 years were 99.3%, 99.0%, and 98.4%, respectively, and at the patient
level, they were 98.6%, 97.7%, and 95.9%, respectively. After adjustment to
possible confounders, the multivariate analysis identified a relationship between
the following risk indicators for implant failure: implant location, length and
design, timing of implantation, bone grafting procedures and gender. Tissue-Level
implants (n = 3863) had a very high survival rate of 99% at 3 years, which was
maintained over the entire study period. Bone-Level implants (n = 600) were as
predictable with a survival rate of 99% up to 3 years, while Tapered Effect
implants (n = 128) demonstrated a lower survival rate of 95% at 5 years. Short 6
mm implants in the mandibular posterior sites had a high survival rate of 100%,
while in maxillary posterior positions a survival rate of only 87% was achieved.
Patient factors such as smoking, autoimmune disease, and penicillin allergy were
tending to associate with higher failure rates. CONCLUSION: High long-term
survival rates were observed for a large cohort of Straumann implants. Tissue-
and Bone-Level implants had higher survival rates than Tapered Effect implants,
and although short implants faired well in the mandibular posterior sites, they
faired less well in the maxillary posterior sites. The study represents private
practice insight into large-scale, long-term implant results.
PMID- 25134416
TI - Quantification of nitrate sources to an urban stream using dual nitrate isotopes.
AB - Human-engineered landscapes and subsequent altered hydrology affect the fate and
transport of reactive nitrogen, particularly in urban watersheds. In this study,
we used dual-nitrate isotopes and mixing model analysis (delta(15)N and
delta(18)O of NO3(-)) to quantify nitrogen inputs from two sources concentrated
in urban systems, sewage and atmospheric deposition. Analysis was conducted on
samples collected from Nine Mile Run (Pittsburgh, PA) including over two years of
samples collected biweekly and samples collected through the hydrographs of four
storm events. Mixing models incorporated uncertainties in the isotopic
composition of potential nitrate sources and resolved the relative proportions of
nitrate inputs from each source using Bayesian techniques. The results indicate
that up to 94% of nitrate in streamwater originated from sewage sources during
baseflow conditions. During storms, atmospheric deposition was a substantial
nitrate source (~ 34%) to total event-based nitrate loads, although sewage
derived nitrate remained the dominant source (66%). The potential influence of
denitrification was considered by incorporating associated isotopic
fractionations into mixing models; up to 19% of sewage-derived samples showed the
isotopic effects of denitrification. This study quantitatively delineates
proportions of nitrate from different sources to urban streamwater, while
incorporating remaining uncertainties in source endmember compositions.
PMID- 25134418
TI - High pressure study of Li-doped fullerides, Li(x)C60 (x = 4,12), by x-ray
diffraction and Raman spectroscopy.
AB - In this article we study the alkali metal-intercalated 2D polymeric Li4C60 and
the monomeric Li12C60 under pressure up to 40 GPa at room temperature, using x
ray diffraction and Raman spectroscopy. Li4C60 undergoes several transitions in
the studied pressure range. At pressures lower than 8 GPa, we observed changes in
both diffraction patterns and Raman scattering spectra, probably due to the
displacement of Li atoms. At 8 GPa another structural and electronic transition
occurs. We observe an enhancement of background and a broadening of diffraction
peaks. Raman modes weaken and broaden considerably. An important structural
transition occurs at around 16 GPa, in which new Raman bands exhibit features
similar to those of a reported 3D C60 polymeric structure. The XRD data shows a
collapse in volume with the simultaneous formation of amorphous material. The
cell parameters deviate from their early pressure evolution and become less
compressible. The high pressure study of highly doped monomeric Li12C60 shows
that its structural integrity is retained up to 13 GPa, with increasing pressure
induced structural distortion and disorder. Above 13 GPa, Li12C60 transforms to a
highly disordered state.
PMID- 25134417
TI - Up-regulation on cytochromes P450 in rat mediated by total alkaloid extract from
Corydalis yanhusuo.
AB - BACKGROUND: Yanhusuo (Corydalis yanhusuo W.T. Wang; YHS), is a well-known
traditional Chinese herbal medicine, has been used in China for treating pain
including chest pain, epigastric pain, and dysmenorrhea. Its alkaloid ingredients
including tetrahydropalmatine are reported to inhibit cytochromes P450 (CYPs)
activity in vitro. The present study is aimed to assess the potential of total
alkaloid extract (TAE) from YHS to effect the activity and mRNA levels of five
cytochromes P450 (CYPs) in rat. METHODS: Rats were administered TAE from YHS (0,
6, 30, and 150 mg/kg, daily) for 14 days, alanine aminotransferase (ALT) levels
in serum were assayed, and hematoxylin and eosin-stained sections of the liver
were prepared for light microscopy. The effects of TAE on five CYPs activity and
mRNA levels were quantitated by cocktail probe drugs using a rapid
chromatography/tandem mass spectrometry (LC-MS/MS) method and reverse
transcription-polymerase chain reaction (RT-PCR), respectively. RESULTS: In
general, serum ALT levels showed no significant changes, and the histopathology
appeared largely normal compared with that in the control rats. At 30 and 150
mg/kg TAE dosages, an increase in liver CYP2E1 and CYP3A1 enzyme activity were
observed. Moreover, the mRNA levels of CYP2E1 and CYP3A1 in the rat liver, lung,
and intestine were significantly up-regulated with TAE from 6 and 30 mg/kg,
respectively. Furthermore, treatment with TAE (150 mg/kg) enhanced the activities
and the mRNA levels of CYP1A2 and CYP2C11 in rats. However, the activity or mRNA
level of CYP2D1 remained unchanged. CONCLUSIONS: These results suggest that TAE
induced CYPs activity in the rat liver results from the elevated mRNA levels of
CYPs. Co-administration of prescriptions containing YHS should consider a
potential herb (drug)-drug interaction mediated by the induction of CYP2E1 and
CYP3A1 enzymes.
PMID- 25134419
TI - Survival of Escherichia coli O157:H7 during manufacture and storage of white
brined cheese.
AB - Escherichia coli O157:H7 is a major foodborne pathogen that causes severe disease
in humans. Survival of E. coli O157:H7 during processing and storage of white
brined cheese was investigated. Cheeses were prepared using pasteurized milk
inoculated with a 4 strain E. coli O157:H7 cocktail (7 log(10) CFU/g) with or
without yogurt starter culture (Lactobacillus delbrueckii ssp. bulgaricus and
Streptococcus salivarius ssp. thermophilus) and stored in 10% or 15% NaCl brine
at 10 and 21 oC for 28 d. NaCl concentration, water activity (a(w)), pH, and
numbers of E. coli O157:H7 and lactic acid bacteria (LAB) were determined in
cheese and brine. E. coli O157:H7 was able to survive in cheese stored in both
brines at 10 and 21 oC regardless of the presence of starter LAB, although the
latter significantly enhanced E. coli O157:H7 reduction in cheese or its brine at
10 oC. E. coli O157:H7 numbers were reduced by 2.6 and 3.4 log(10) CFU/g in
cheese stored in 10% and 15% NaCl brine, respectively, in the presence of starter
LAB and by 1.4 and 2.3 log(10) CFU/g, respectively, in the absence of starter LAB
at 10 oC. The pathogen survived, but at lower numbers in the brines. The salt
concentration of cheese stored in 10% brine remained about 5% during ripening,
but in 15% brine, the NaCl level increased 1.6% to 8.1% (w/w) by 28 d. Values of
pH and a(w) slightly decreased 1 d after exposure to brine and reached 5.5 to 6.6
and 0.88 to 0.94, respectively, in all treatments.
PMID- 25134420
TI - What is your diagnosis? Perianal gland mass in a cat. Anal sac gland carcinoma.
PMID- 25134421
TI - Characteristics associated with drug-induced liver injury from interferon beta in
multiple sclerosis patients.
AB - OBJECTIVE: To identify and characterize drug-induced liver injury (DILI)
associated with IFN-beta in multiple sclerosis (MS) using recommended criteria.
METHODS: This retrospective, mixed methods design included a cohort of IFN-beta
exposed MS patients from British Columbia (BC), Canada and a series of DILI cases
from other Canadian provinces and two adverse drug reaction (ADR) networks (USA
and Sweden). Associations between sex, age and IFN-beta product, and DILI were
explored in BC cohort using Cox proportional hazard analyses. Characteristics,
including the time to DILI, were compared between sites. RESULTS: In BC, 18/942
(1.9%) of IFN-beta exposed MS patients met criteria for DILI, with a trend toward
an increased risk for women and those exposed to IFN-beta-1a SC (44 mcg 3 *
weekly) (adjusted Hazard Ratios: 3.15;95% CI:0.72 - 13.72, p = 0.13 and
6.26;95%CI:0.78 - 50.39, p = 0.08, respectively). Twenty-four additional cases
were identified from other sites; the median time to DILI was comparable between
BC and other Canadian cases (105 and 90 days, respectively), but longer for the
ADR network cases (590 days, p = 0.006). CONCLUSIONS: Approximately 1 in 50 IFN
beta exposed patients developed DILI in BC, Canada. Identification of DILI cases
from diverse sources highlighted that this reaction occurs even after years of
exposure.
PMID- 25134422
TI - Compression therapy: scientific background and practical applications.
AB - BACKGROUND: Compression bandaging is the most prevalent form of treatment for
venous leg ulcers. Successful treatment requires knowledge of the appropriate
materials and the ability to employ them following current guidelines. This study
investigates German health-care providers for their knowledge of bandage
materials and their practical ability in applying short-stretch compression
bandages. PARTICIPANTS AND METHODS: Within the framework of nationwide practical
education on compression therapy, the participants' knowledge was quantified by
asking standardized questions. Furthermore, their practical ability was evaluated
by having them apply compression bandages within a pressure range of 50-60 mmHg.
Another criterion was the pressure drop after a four-time dorsiflexion. RESULTS:
Overall, 891 providers (3.3 % physicians, 5.5 % medical assistants, 90.7 %
nursing staff) participated. Within the practical test only few (just under 10%)
applied the bandages with the intended pressure; 77.0 % applied them below and
13.7 % above the target pressure. After a four-time dorsiflexion there was an
average pressure drop of 6.7 mmHg. Surveying the participant's skills revealed
that only 11.9 % knew about padding beneath compression bandages, 15.0 % knew of
multi-component systems, and 14.8 % were familiar with ulcer stocking systems.
CONCLUSIONS: Clearly, compression material and its application are unfamiliar to
most practice employees. Without question there are deficits in the provision of
compression therapy.
PMID- 25134424
TI - How does drag affect the underwater phase of a swimming start?
AB - During the underwater phase of the swimming start drag forces are constantly
acting to slow the swimmer down. The current study aimed to quantify total drag
force as well as the specific contribution of wave drag during the underwater
phase of the swimming start. Swimmers were towed at three different depths
(surface, 0.5 m, 1.0 m) and four speeds (1.6, 1.9, 2.0, 2.5 m . s(-1)), totaling
12 conditions. Wave drag and total drag were measured for each trial. Mixed
modeling and plots were then used to determine the relationships between each
towing condition and the amount of drag acting on the swimmer. The results of
this study show large decreases in total drag as depth increases, regardless of
speed (-19.7% at 0.5 m and -23.8% at 1.0 m). This is largely due to the
significant reduction in wave drag as the swimmers traveled at greater depth. It
is recommended that swimmers travel at least 0.5 m below the surface to avoid
excessive drag forces. Swimmers should also perform efficient breakouts when
transitioning into free swimming to reduce the duration spent just below the
surface where drag values are reported at their highest.
PMID- 25134423
TI - Co-occurrence of transcription and translation gene regulatory features underlies
coordinated mRNA and protein synthesis.
AB - BACKGROUND: Variability in protein levels is generated through intricate control
of the different gene decoding phases. Presently little is known about the links
between the various gene expression stages. Here we investigated the relationship
between transcription and translation regulatory properties encoded in mammalian
genes. RESULTS: We found that the TATA-box, a core promoter element known to
enhance transcriptional output, is associated not only with higher mRNA levels
but also with positive translation regulatory features and elevated translation
efficiency. Further investigation revealed general association between
transcription and translation regulatory trends. Specifically, translation
inhibitory features such as the presence of upstream AUG (uAUG) and increased
lengths of the 5'UTR, the coding sequence and the 3'UTR, are strongly associated
with lower translation as well as lower transcriptional rate. CONCLUSIONS: Our
findings reveal that co-occurrence of several gene-encoded transcription and
translation regulatory features with the same trend substantially contributes to
the final mRNA and protein expression levels and enables their coordination.
PMID- 25134425
TI - Common misconceptions about data analysis and statistics.
PMID- 25134426
TI - Relationship between buckling of acupuncture needles and the handle type.
AB - BACKGROUND: Most popular single-use acupuncture needles consist of a stainless
steel shaft with a handle made of copper coil or plastic stick. OBJECTIVES: To
determine the strengths and weaknesses of these two handle types for needle
buckling. METHODS: The buckling load for acupuncture needles with these two
different handle types was determined using a digital scale, and the stiffness of
stainless steel wires used in different types of acupuncture needles was measured
using a Dynamic Mechanical Analysis machine. RESULTS: This study showed that an
acupuncture needle with a copper coil handle was far more susceptible to buckling
than a needle with a plastic stick handle. The average buckling force of
acupuncture needles with plastic stick handles was 46.7% higher than that with
copper coil handles for needles of 0.25 mm*30 mm, and 30.8% higher for needles of
0.25 mm*60 mm. Replacing a copper coil handle with a plastic stick handle could
save about 100 tonnes of copper wires and 20 million metres of medical grade
stainless steel wire a year worldwide. CONCLUSIONS: The results from this study
suggest that the common practice of using coiled copper for handles on
acupuncture needles should be re-evaluated. Replacing a copper coil handle with a
plastic stick handle would significantly reduce needle buckling and improve
patient comfort and safety. This would also reduce the consumption of copper and
medical grade stainless steel wire considerably.
PMID- 25134427
TI - Development of an evidence-based exercise programme for people with hand
osteoarthritis.
AB - BACKGROUND: Exercising is recommended for people with hand osteoarthritis (HOA),
but there is no consensus regarding the design of exercise programmes. OBJECTIVE:
To describe the development and content of an evidence-based exercise programme
for people with HOA. METHODS: The development was based on research evidence,
professional expertise, and client evidence and adhered to the new Medical
Research Council framework for design and evaluation of complex interventions.
The process included literature search and appraisal, discussions with clinicians
and patient research partners, and piloting, followed by a revision of the
programme based on feedback from pilot participants. RESULTS: The programme
contains three exercises to increase the strength and stability of the shoulder,
arm and wrist muscles, and four exercises to maintain or increase range of
motion, grip strength, and joint stability in the finger joints. It starts with a
warm-up period, ends with a finger stretch exercise, and follows the American
College of Sports Medicine's recommendations regarding exercise intensity,
session frequency, and length of exercise period. An exercise diary is included
as part of the programme. CONCLUSIONS: An evidence-based exercise programme for
people with HOA has been developed. The effect of the programme has recently been
evaluated in a randomized controlled trial.
PMID- 25134428
TI - Structure-activity relationships of N-benzylsalicylamides for inhibition of
photosynthetic electron transport.
AB - Inhibition of photosynthetic electron transport (PET) in spinach chloroplasts by
sixty-one ring-substituted N-benzylsalicylamides was investigated. The inhibitory
potency of the compounds expressed by IC50 value varied from 2.0 to 425.3
MUmol/L. Several evaluated compounds can be considered as effective PET
inhibitors; these include N-(3,4- dichlorobenzyl)-2-hydroxy-5-nitrobenzamide
(IC50 = 2.0 MUmol/L), 3,5-dibromo-N-(3,4-dichlorobenzyl)-2-hydroxybenzamide (IC50
= 2.3 MUmol/L) and 3,5-dibromo-N-(4-chlorobenzyl)-2-hydroxybenzamide (IC50 = 2.6
MUmol/L) with activity comparable with that of the standard Diuron (IC50 = 1.9
MUmol/L). The PET inhibiting activity increased approximately linearly with
increasing lipophilicity of the compounds as well as with the increasing sum of
Hammett sigma constants of the substituents on the acyl fragment (R(1) = H, 5
OCH3, 5-CH3, 5-Cl, 5-Br, 5-NO2, 4-OCH3, 4-Cl, 3,5-Cl and 3,5-Br) and the
benzylamide fragment (R(2) = H, 4-OCH3, 4-CH3, 4-F, 4-Cl and 3,4-Cl). Based on
the evaluated structure-PET inhibiting activity relationships (QSAR) it was
confirmed that the inhibitory activity of the compounds depends on lipophilicity
(log P or distributive parameters pi; (1) and pi(2)of individual substituents)
and electronic properties of the substituents on the acyl (sigma(1)) and the
benzylamide fragments (sigma(2)), the contribution of sigma(1) being more
significant than that of sigma(2).
PMID- 25134429
TI - Design, synthesis, and antitumor activity of novel acylate of 6-OH at 1- O
acetylbritannilactone.
AB - N-(alpha-Alkyloxime-3-phenylpropionyl) proline was designed and synthesized as an
acylating agent to modify the 6-OH of 1-O-acetylbritannilactone. Eight
intermediates and eight target compounds were obtained. The structures of sixteen
novel compounds were characterized by (1)HNMR, IR and HRMS. The activities
against HL-60 and Bel-7402 cell lines were tested, the IC50 values of compound
IVg were 2.7 MUM and 4.3 MUM, respectively.
PMID- 25134430
TI - Synthesis and evaluation of benzimidazole derivatives as selective COX-2
inhibitors.
AB - A new series of 1-{(5-substituted-alkyl/aryl-1,3,4-oxadiazol-2-yl)methyl}-2
(piperidin-1-ylmethyl)-1Hbenzimidazoles (5a-5r) was synthesized and screened for
their inhibitory activity against COX (1 and 2). In vivo antiinflammatory
activity of potent compounds was done by carrageenan-induced rat paw edema model.
In vitro anticancer activity of synthesized compounds was also performed at the
National Cancer Institute (NCI) against NCI 60 cell lines panel. Out of the 18
compounds screened, 5h, 5i, 5j and 5l were found to be potent COX-2 inhibitors in
the range of IC50 0.06-0.81 MUM. In vivo anti-inflammatory screening results
revealed that the compounds 5h and 5j manifested profound percent protection of
72.8 and 75.0%, respectively. Compound 5f exhibited moderate cytotoxicity with
58.79% growth inhibition against SNB-75 (CNS Cancer) cell lines and moderate
activity against COX-2 (IC50 = 8.0 MUM).
PMID- 25134431
TI - Continuing professional development training needs of medical laboratory
personnel in Botswana.
AB - BACKGROUND: Laboratory professionals are expected to maintain their knowledge on
the most recent advances in laboratory testing and continuing professional
development (CPD) programs can address this expectation. In developing countries,
accessing CPD programs is a major challenge for laboratory personnel, partly due
to their limited availability. An assessment was conducted among clinical
laboratory workforce in Botswana to identify and prioritize CPD training needs as
well as preferred modes of CPD delivery. METHODS: A self-administered
questionnaire was disseminated to medical laboratory scientists and technicians
registered with the Botswana Health Professions Council. Questions were organized
into domains of competency related to (i) quality management systems, (ii)
technical competence, (iii) laboratory management, leadership, and coaching, and
(iv) pathophysiology, data interpretation, and research. Participants were asked
to rank their self-perceived training needs using a 3-point scale in order of
importance (most, moderate, and least). Furthermore, participants were asked to
select any three preferences for delivery formats for the CPD. RESULTS: Out of
350 questionnaires that were distributed, 275 were completed and returned giving
an overall response rate of 79%. The most frequently selected topics for training
in rank order according to key themes were (mean, range) (i) quality management
systems, most important (79%, 74-84%); (ii) pathophysiology, data interpretation,
and research (68%, 52-78%); (iii) technical competence (65%, 44-73%); and (iv)
laboratory management, leadership, and coaching (60%, 37-77%). The top three
topics selected by the participants were (i) quality systems essentials for
medical laboratory, (ii) implementing a quality management system, and (iii)
techniques to identify and control sources of error in laboratory procedures. The
top three preferred CPD delivery modes, in rank order, were training workshops,
hands-on workshops, and internet-based learning. Journal clubs at the workplace
was the least preferred method of delivery of CPD credits. CONCLUSIONS: CPD
programs to be developed should focus on topics that address quality management
systems, case studies, competence assessment, and customer care. The findings
from this survey can also inform medical laboratory pre-service education
curriculum.
PMID- 25134432
TI - Re-development of mental health first aid guidelines for non-suicidal self
injury: a Delphi study.
AB - BACKGROUND: Up to 12% of Australian adults and almost one in five adolescents are
estimated to have engaged in non-suicidal self-injury (NSSI) at some time in
their life. Friends and family are most likely to notice signs of NSSI, but may
be unsure how to intervene. Mental health first aid guidelines were developed in
2008 on how to do this through providing initial support and encouraging
appropriate professional help-seeking. This study aims to re-develop the 2008
NSSI first aid guidelines to ensure they contain current recommended helping
actions and remain consistent with the NSSI intervention literature. METHODS: The
Delphi consensus method was used to determine the importance of the inclusion of
helping statements in the guidelines. These statements describe helping actions a
member of the public can take, and information they should have, to help someone
who is engaging in NSSI. Systematic searches of the available NSSI intervention
literature were conducted to find helping statements. Two expert panels,
comprising 28 NSSI professionals and 33 consumer advocates, rated the importance
of each statement. RESULTS: 98 out of 220 statements were endorsed as appropriate
helping actions in providing assistance to someone engaging in NSSI. These
statements were used to form the updated mental health first aid guidelines for
NSSI. CONCLUSION: The re-development of the guidelines has resulted in more
comprehensive guidance than the original version (98 versus 30 statements
containing helping actions). This substantial increase in endorsed statements
adds detail and depth to the guidelines, as well as covers additional ways of
providing guidance and support.
PMID- 25134435
TI - A physical model of sprinting.
AB - A new physical model of all-out sprinting is presented. The first models for the
applied forces in the block, drive and maintenance phases, as well as for braking
forces, are proposed and are based on experimental observations. The applied
forces and the aerodynamic drag forces along with the speed and position of the
sprinter are calculated by the model as functions of time. The model's unknown
parameters are physically relevant and are quantitatively comparable to
quantities measured experimentally. A novel mathematical method, not based on
curve fitting, is proposed along with the model which requires two observable
quantities, time of first step and start of maintenance phase, and four time
splits. The model was validated by modeling several elite sprints from available
split data, as well as measured splits for non-elite sprinters, over 100 m and
200 m distances. Excellent agreement between the split times and the simulated
times was obtained and the model was shown to accurately predict 100 m times from
60 m splits for non-elite runners and 200 m times from 100 m splits for elite
sprinters. The model was also applied to the study of wind and altitude effects
for elite sprinters in 100 and 200 m sprints. The model presented in this paper
may also be useful as a coaching tool for non-elite sprinters by enabling
comparisons with elite sprinters, the identification of weaknesses (comparing
phases, braking coefficient) and by allowing predictions of 100 m times based on
60 m (indoor) performances and 200 m times based on 100 m splits.
PMID- 25134433
TI - Variable NF-kappaB pathway responses in colon cancer cells treated with
chemotherapeutic drugs.
AB - BACKGROUND: The nuclear factor kappa-light-chain-enhancer of activated B cells
(NF-kappaB) signaling pathway is activated in cells exposed to various stimuli,
including those originating on the cell surface or in the nucleus. Activated NF
kappaB signaling is thought to enhance cell survival in response to these
stimuli, which include chemotherapy and radiation. In the present effort, we
determined which anticancer drugs preferentially activate NF-kappaB in colon
cancer cells. METHODS: NF-kappaB reporter cells were established and treated with
5-fluorouracil (5-FU, DNA/RNA damaging), oxaliplatin (DNA damaging), camptothecin
(CTP, topoisomerase inhibitor), phleomycin (radiomimetic), or erlotinib (EGFR
inhibitor). The activation of NF-kappaB was assessed by immunofluorescence for
p65 translocation, luciferase assays, and downstream targets of NF-kappaB
activation (cIAP2, and Bcl-XL) were evaluated by immunoblotting, by ELISA (CXCL8
and IL-6 in culture supernatants), or by gene expression analysis. RESULTS: Colon
cancer cells responded variably to different classes of therapeutic agents, and
these agents initiated variable responses among different cell types. CPT
activated NF-kappaB in SW480 colon cancer cells in a dose-dependent manner, but
not in HCT116 cells that were either wild-type or deficient for p53. In SW480
colon cancer cells, NF-kappaB activation by CPT was accompanied by secretion of
the cytokine CXCL8, but not by up-regulation of the anti-apoptotic genes, cIAP2
or Bcl-XL. On the contrary, treatment of HCT116 cells with CPT resulted in up
regulation of CXCR2, a receptor for CXCL8, without an increase in cytokine
levels. In SW480 cells, NF-kappaB reporter activity, but not cytokine secretion,
was inhibited by SM-7368, an NF-kappaB inhibitor. CONCLUSION: The results show
that, in response to cancer therapeutic agents, NF-kappaB activation varies with
the cellular make up and that drug-induced NF-kappaB activation may be
functionally uncoupled from anti-apoptotic outcomes found for other stimuli. Some
cancer cells in a heterogeneous tumor tissue may, under therapeutic pressure,
release soluble factors that have paracrine activity on neighboring cells that
express the cognate receptors.
PMID- 25134434
TI - Continuum description of the Poisson's ratio of ligament and tendon under finite
deformation.
AB - Ligaments and tendons undergo volume loss when stretched along the primary fiber
axis, which is evident by the large, strain-dependent Poisson's ratios measured
during quasi-static tensile tests. Continuum constitutive models that have been
used to describe ligament material behavior generally assume incompressibility,
which does not reflect the volumetric material behavior seen experimentally. We
developed a strain energy equation that describes large, strain dependent
Poisson's ratios and nonlinear, transversely isotropic behavior using a novel
method to numerically enforce the desired volumetric behavior. The Cauchy stress
and spatial elasticity tensors for this strain energy equation were derived and
implemented in the FEBio finite element software (www.febio.org). As part of this
objective, we derived the Cauchy stress and spatial elasticity tensors for a
compressible transversely isotropic material, which to our knowledge have not
appeared previously in the literature. Elastic simulations demonstrated that the
model predicted the nonlinear, upwardly concave uniaxial stress-strain behavior
while also predicting a strain-dependent Poisson's ratio. Biphasic simulations of
stress relaxation predicted a large outward fluid flux and substantial relaxation
of the peak stress. Thus, the results of this study demonstrate that the
viscoelastic behavior of ligaments and tendons can be predicted by modeling fluid
movement when combined with a large Poisson's ratio. Further, the constitutive
framework provides the means for accurate simulations of ligament volumetric
material behavior without the need to resort to micromechanical or homogenization
methods, thus facilitating its use in large scale, whole joint models.
PMID- 25134436
TI - Simple finite element models for use in the design of therapeutic footwear.
AB - Therapeutic footwear is frequently prescribed in cases of rheumatoid arthritis
and diabetes to relieve or redistribute high plantar pressures in the region of
the metatarsal heads. Few guidelines exist as to how these interventions should
be designed and what effect such interventions actually have on the plantar
pressure distribution. Finite element analysis has the potential to assist in the
design process by refining a given intervention or identifying an optimal
intervention without having to actually build and test each condition. However,
complete and detailed foot models based on medical image segmentation have proven
time consuming to build and computationally expensive to solve, hindering their
utility in practice. Therefore, the goal of the current work was to determine if
a simplified patient-specific model could be used to assist in the design of foot
orthoses to reduce the plantar pressure in the metatarsal head region. The
approach is illustrated by a case study of a diabetic patient experiencing high
pressures and pain over the fifth metatarsal head. The simple foot model was
initially calibrated by adjusting the individual loads on the metatarsals to
approximate measured peak plantar pressure distributions in the barefoot
condition to within 3%. This loading was used in various shod conditions to
identify an effective orthosis. Model results for metatarsal pads were
considerably higher than measured values but predictions for uniform surfaces
were generally within 16% of measured values. The approach enabled virtual
prototyping of the orthoses, identifying the most favorable approach to
redistribute the patient's plantar pressures.
PMID- 25134438
TI - Transition-metal-catalyzed ring expansion of diazocarbonylated cyclic N
hydroxylamines: a new approach to cyclic ketonitrones.
AB - Novel C-ethoxycarbonyl cyclic ketonitrones are synthesized from the Ag- or Cu
catalyzed ring expansion of beta-diazo cyclic hydroxylamines. The latter are
themselves easily obtained by the addition of lithiated ethyl diazoacetate onto
cyclic nitrones. The regioselective metal-catalyzed rearrangement of beta-diazo
cyclic hydroxylamines proved highly efficient and resulted in a synthetically
useful ring expansion to produce 6- or 7-membered ring functionalized nitrones.
The outcome of the two steps, i.e. nucleophilic addition of alpha-diazoesters to
nitrones and ring expansion, is a formal nitrone homologation.
PMID- 25134437
TI - Cigarette smoke extract-induced BEAS-2B cell apoptosis and anti-oxidative Nrf-2
up-regulation are mediated by ROS-stimulated p38 activation.
AB - Cigarette smoke contains reactive oxygen (ROS) that can cause oxidative stress.
It increases the number of apoptotic and necrotic lung cells and further induces
the development of chronic airway disease. In this study, we investigated the
effects of cigarette smoke extract (CSE) on apoptosis in human bronchial
epithelial cells (BEAS-2B). CSE exposure induced ROS generation and p38 mitogen
activated protein kinase (MAPK) activation that are associated with the
activation of apoptosis-regulating signal kinase 1 (ASK-1). N-acetylcysteine (a
general antioxidant) attenuated the CSE-induced ASK-1 and p38 MAPK activation and
cell apoptosis, suggesting a triggering role of ROS in ASK-1/p38 MAPK activation
during apoptotic progression. In contrast, the inhibition and knockdown of p38
attenuated the expression of anti-oxidant master NF-E2-related factor 2 (Nrf-2)
and CSE-induced apoptosis, suggesting that p38 MAPK modulates Nrf-2 expression
and presumably prevents cell apoptosis. Taken together, the data presented in
this manuscript demonstrate that the ROS-dependent ASK-1/p38 signaling cascade
regulates CSE-induced BEAS-2B cell apoptosis. In addition, anti-oxidative Nrf-2
is also up-regulated by the ROS/p38 signaling cascade in this progression.
PMID- 25134439
TI - Pathogen reduction by ultraviolet C light effectively inactivates human white
blood cells in platelet products.
AB - BACKGROUND: Residual white blood cells (WBCs) in cellular blood components induce
a variety of adverse immune events, including nonhemolytic febrile transfusion
reactions, alloimmunization to HLA antigens, and transfusion-associated graft
versus-host disease (TA-GVHD). Pathogen reduction (PR) methods such as the
ultraviolet C (UVC) light-based THERAFLEX UV-Platelets system were developed to
reduce the risk of transfusion-transmitted infection. As UVC light targets
nucleic acids, it interferes with the replication of both pathogens and WBCs.
This preclinical study aimed to evaluate the ability of UVC light to inactivate
contaminating WBCs in platelet concentrates (PCs). STUDY DESIGN AND METHODS: The
in vitro and in vivo function of WBCs from UVC-treated PCs was compared to that
of WBCs from gamma-irradiated and untreated PCs by measuring cell viability,
proliferation, cytokine secretion, antigen presentation in vitro, and xenogeneic
GVHD responses in a humanized mouse model. RESULTS: UVC light was at least as
effective as gamma irradiation in preventing GVHD in the mouse model. It was more
effective in suppressing T-cell proliferation (>5-log reduction in the limiting
dilution assay), cytokine secretion, and antigen presentation than gamma
irradiation. CONCLUSIONS: The THERAFLEX UV-Platelets (MacoPharma) PR system can
substitute gamma irradiation for TA-GVHD prophylaxis in platelet (PLT)
transfusion. Moreover, UVC treatment achieves suppression of antigen presentation
and inhibition of cytokine accumulation during storage of PCs, which has
potential benefits for transfusion recipients.
PMID- 25134441
TI - Effects of sample injection amount and time-of-flight mass spectrometric
detection dynamic range on metabolome analysis by high-performance chemical
isotope labeling LC-MS.
AB - The effect of sample injection amount on metabolome analysis in a chemical
isotope labeling (CIL) liquid chromatography-mass spectrometry (LC-MS) platform
was investigated. The performance of time-of-flight (TOF) mass spectrometers with
and without a high-dynamic-range (HD) detection system was compared in the
analysis of (12)C2/(13)C2-dansyl labeled human urine samples. An average of 1635
+/- 21 (n = 3) peak pairs or putative metabolites was detected using the HD-TOF
MS, compared to 1429 +/- 37 peak pairs from a conventional or non-HD TOF-MS. In
both instruments, signal saturation was observed. However, in the HD-TOF-MS,
signal saturation was mainly caused by the ionization process, while in the non
HD TOF-MS, it was caused by the detection process. To extend the MS detection
range in the non-HD TOF-MS, an automated switching from using (12)C to (13)C
natural abundance peaks for peak ratio calculation when the (12)C peaks are
saturated has been implemented in IsoMS, a software tool for processing CIL LC-MS
data. This work illustrates that injecting an optimal sample amount is important
to maximize the metabolome coverage while avoiding the sample carryover problem
often associated with over-injection. A TOF mass spectrometer with an enhanced
detection dynamic range can also significantly increase the number of peak pairs
detected. BIOLOGICAL SIGNIFICANCE: In chemical isotope labeling (CIL) LC-MS,
relative metabolite quantification is done by measuring the peak ratio of a
(13)C2-/(12)C2-labeled peak pair for a given metabolite present in two
comparative samples. The dynamic range of peak ratio measurement does not need to
be very large, as only subtle changes of metabolite concentrations are
encountered in most metabolomic studies where relative metabolome quantification
of different groups of samples is performed. However, the absolute concentrations
of different metabolites can be very different, requiring a technique to provide
a wide detection dynamic range to allow the detection of as many peak pairs as
possible. In this work, we demonstrated that controlling the sample injection
amount into LC-MS was critical to achieve the optimal detectability while
avoiding sample carry-over problem. In addition, the use of a high-dynamic-range
TOF system increased the number of peak pairs detected, compared to a
conventional TOF system. We also investigated the ionization and detection
saturation factors limiting the dynamic range of detection. This article is part
of a Special Issue entitled: Protein dynamics in health and disease. Guest
Editors: Pierre Thibault and Anne-Claude Gingras.
PMID- 25134443
TI - Preventing primary cesareans: implications for laboring women, their partners,
nurses, educators, and doulas.
PMID- 25134442
TI - Can we safely reduce primary cesareans with greater patience?
PMID- 25134445
TI - Family-centered neonatal intensive care.
PMID- 25134440
TI - Acute kidney injury in major gynaecological surgery: an observational study.
AB - OBJECTIVE: To assess the prevalence, outcomes and cost associated with acute
kidney injury (AKI) defined by consensus risk, injury, failure, loss, and end
stage kidney (RIFLE) criteria after gynaecologic surgery. DESIGN: Retrospective
single-centre cohort study. SETTING: Academic medical centre. SAMPLE: Two
thousand three hundred and forty-one adult women undergoing major inpatient
gynaecologic surgery between January 2000 and November 2010. METHODS: AKI was
defined by RIFLE criteria as an increase in serum creatinine greater than or
equal to 50% from the reference creatinine. We used multivariable regression
analyses to determine the association between perioperative factors, AKI,
mortality and cost. MAIN OUTCOME MEASURES: AKI, combined major adverse events
(hospital mortality, sepsis or mechanical ventilation), 90-day mortality and
hospital cost. RESULTS: Overall prevalence of AKI was 13%. The prevalence of AKI
was associated with the primary diagnosis. Of women with benign tumour surgeries,
5% (43/801) experienced AKI compared with 18% (211/1159) of women with malignant
disease (P < 0.001). Only 1.3% of the whole cohort had evidence of urologic
mechanical injury. In a multivariable logistic regression analysis, AKI patients
had nine times the odds of a major adverse event compared to patients without AKI
(adjusted odds ratio 8.95, 95% confidence interval 5.27-15.22). We have
identified several readily available perioperative factors that can be used to
identify patients at high risk for AKI after in-hospital gynaecologic surgery.
CONCLUSIONS: AKI is a common complication after major inpatient gynaecologic
surgery associated with an increase in resource utilisation and hospital cost,
morbidity and mortality.
PMID- 25134447
TI - The role of carbonic anhydrase VI in bitter taste perception: evidence from the
Car6-/- mouse model.
AB - BACKGROUND: Carbonic anhydrase VI (CA VI) is a secretory isozyme of the alpha-CA
gene family. It is highly expressed in the salivary and mammary glands and
secreted into saliva and milk. Although CA VI was first described as a gustatory
protein, its exact functional roles have remained enigmatic. Interestingly,
polymorphism of the CA6 gene was recently linked to bitter taste perception in
humans. In this study, we compared the preference of Car6-/- and wild-type mice
for different taste modalities in an IntelliCage monitoring environment.
Morphologies of taste buds, tongue papillae, and von Ebner's glands were
evaluated by light microscopy. Cell proliferation and rate of apoptosis in tongue
specimens were examined by Ki67 immunostaining and fluorescent DNA fragmentation
staining, respectively. RESULTS: The behavioral follow up of the mice in an
IntelliCage system revealed that Car6-/- mice preferred 3 MUM quinine (bitter)
solution, whereas wild type mice preferred water. When the quinine concentration
increased, both groups preferentially selected water. Histological analysis, Ki67
immunostaining and detection of apoptosis did not reveal any significant changes
between tongue specimens of the knockout and wild type mice. CONCLUSIONS: Our
knockout mouse model confirms that CA VI is involved in bitter taste perception.
CA VI may be one of the factors which contribute to avoidance of bitter,
potentially harmful, substances.
PMID- 25134448
TI - Rapamycin protects kidney against ischemia reperfusion injury through recruitment
of NKT cells.
AB - BACKGROUND: NKT cells play a protective role in ischemia reperfusion (IR) injury,
of which the trafficking in the body and recruitment in injured organs can be
influenced by immunosuppressive therapy. Therefore, we investigated the effects
of rapamycin on kidneys exposed to IR injury in early stage and on trafficking of
NKT cells in a murine model. MATERIAL AND METHODS: Balb/c mice were subjected to
kidney 30 min ischemia followed by 24 h reperfusion. Rapamycin (2.5 ml/kg) was
administered by gavage daily, starting 1 day before the operation. Renal function
and histological changes were assessed. The proportion of NKT cells in peripheral
blood, spleen and kidney was detected by flow cytometry. The chemokines and
corresponding receptor involved in NKT cell trafficking were determined by RT-PCR
and flow cytometry respectively. RESULTS: Rapamycin significantly improved renal
function and ameliorated histological injury. In rapamycin-treated group, the
proportion of NKT cells in spleen was significantly decreased but increased in
peripheral blood and kidney. In addition, the CXCR3+ NKT cell in the kidney
increased remarkably in the rapamycin-treated group. The chemokines, CXCL9 and
CXCL10, as the ligands of CXCR3, were also increased in the rapamycin-treated
kidney. CONCLUSIONS: Rapamycin may recruit NKT cells from spleen to the IR
induced kidney to ameliorate renal IR injury in the early stage.
PMID- 25134450
TI - The CROWN Initiative: Journal editors invite researchers to develop core outcomes
in women's health.
PMID- 25134449
TI - The PP4R1 subunit of protein phosphatase PP4 targets TRAF2 and TRAF6 to mediate
inhibition of NF-kappaB activation.
AB - TRAFs constitute a family of proteins that have been implicated in signal
transduction by immunomodulatory cellular receptors and viral proteins. TRAF2 and
TRAF6 have an E3-ubiquitin ligase activity, which is dependent on the integrity
of their RING finger domain and it has been associated with their ability to
activate the NF-kappaB and AP1 signaling pathways. A yeast two-hybrid screen with
TRAF2 as bait, identified the regulatory subunit PP4R1 of protein phosphatase PP4
as a TRAF2-interacting protein. The interaction of TRAF2 with PP4R1 depended on
the integrity of the RING finger domain of TRAF2. PP4R1 could interact also with
the TRAF2-related factor TRAF6 in a RING domain-dependent manner. Exogenous
expression of PP4R1 inhibited NF-kappaB activation by TRAF2, TRAF6, TNF and the
Epstein-Barr virus oncoprotein LMP1. In addition, expression of PP4R1
downregulated IL8 induction by LMP1, whereas downregulation of PP4R1 by RNA
interference enhanced the induction of IL8 by LMP1 and TNF. PP4R1 could mediate
the dephosphorylation of TRAF2 Ser11, which has been previously implicated in
TRAF2-mediated activation of NF-kappaB. Finally, PP4R1 could inhibit TRAF6
polyubiquitination, suggesting an interference with the E3 ubiquitin ligase
activity of TRAF6. Taken together, our data identify a novel mechanism of NF
kappaB pathway inhibition which is mediated by PP4R1-dependent targeting of
specific TRAF molecules.
PMID- 25134452
TI - Psychological distress among parents having offspring with autism spectrum
disorder: Authors' reply.
PMID- 25134451
TI - Paediatric vulvar disease.
AB - Paediatric vulvar skin conditions are relatively common but often cause
diagnostic difficulties for clinicians, which can lead to anxiety within the
children's families. Vulvar skin conditions can be caused by various underlying
aetiologies. Most are general dermatologic conditions that occur in the vulvar
area, such as eczema, psoriasis, skin lesions or infections. However, other
conditions such as lichen sclerosus and napkin dermatitis ('nappy rash') only
affect the genital region. Every affected child needs a sensitive evaluation of
the complaint including an assessment of the impact of the condition on the
patient and her family. Paediatric vulvar disease often influences bowel and
bladder habits and may lead to behavioural problems. General measures such as
avoidance of irritants or soap substitution and regular use of emollients are
helpful for all patients. Specific therapy depends upon the underlying diagnosis.
Time spent reassuring the families, reinforcing regimens and providing written
documentation can all be very helpful in successful management of paediatric
vulvar skin conditions.
PMID- 25134453
TI - The burden of false-positive results in analog and digital screening mammography:
experience of the Nova Scotia Breast Screening Program.
AB - PURPOSE: The Canadian Task Force on Preventive Health Care released
recommendations for breast cancer screening, in part, based on harms associated
with screening. The purpose of this study was to describe the rate of false
positive (FP) screening mammograms and to describe the extent of the
investigations after an FP. METHODS: A cohort was identified that consisted of
all screening mammograms performed through the Screening Program (2000-2011) with
patients ages 40-69 years at screening. Rates of FP screening mammograms were
calculated as well as rates of further investigations required, including
additional imaging, needle core biopsy, and surgery. Analyses were stratified by
10-year age group, screening status (first vs rescreen), and technology. RESULTS:
A total of 608,088 screening mammograms were included. The FP rate varied by age
group, and decreased with increasing age (digital, 40-49 years old, FP = 8.0%; 50
59 years old, FP = 6.3%; 60-69 years old, FP = 4.6%). The FP rate also varied by
screening status (digital, first screen, FP = 12.0%; rescreen, FP = 5.6%), and
this difference was consistent across age groups. The need for further
investigation varied by age group, with invasive procedures being more heavily
used as women age (digital, rescreen group, surgery: 40-49 years old, 1.1%; 50-59
years old 1.6%, 60-69 years old, 1.8%). CONCLUSIONS: Both the FP screening
mammogram rate and the degree to which further investigation was required varied
by age group and screening status. Reporting on these rates should form part of
the evaluation of screening performance.
PMID- 25134455
TI - Is Available Support Always Helpful for Older Adults? Exploring the Buffering
Effects of State and Trait Social Support.
AB - OBJECTIVES: Associations between social support and health are studied since
decades. Yet, little is known about how they vary by state versus trait aspects
of support and by adult age. At trait and state level, the current study
investigates direct associations between social support and health and whether
support buffers the daily negative affect (NA)-health association in 2 age
groups. METHOD: Seventy-nine younger and 88 older adults (OA) participated in 20
daily assessments of NA, health complaints (HC), and available support. On trait
and state levels, 3 support facets-emotional, informational, and instrumental
were distinguished; social integration was assessed on the trait level. RESULTS:
For OA, trait emotional support was associated with fewer HC. In both age groups,
state informational support was related to more daily HC. Social integration
buffered the daily NA-health association in younger adults (YA), whereas
informational support amplified the same association in OA. DISCUSSION: We
propose that 2 different mechanisms are relevant for younger and OA and at state
and trait level. Although emotional support may be a resource for OA,
informational support may enhance their daily complaints. YA seem to benefit from
being socially integrated.
PMID- 25134454
TI - Carotenoids, inflammation, and oxidative stress--implications of cellular
signaling pathways and relation to chronic disease prevention.
AB - Several epidemiologic studies have shown that diets rich in fruits and vegetables
reduce the risk of developing several chronic diseases, such as type 2 diabetes,
atherosclerosis, and cancer. These diseases are linked with systemic, low-grade
chronic inflammation. Although controversy persists on the bioactive ingredients,
several secondary plant metabolites have been associated with these beneficial
health effects. Carotenoids represent the most abundant lipid-soluble
phytochemicals, and in vitro and in vivo studies have suggested that they have
antioxidant, antiapoptotic, and anti-inflammatory properties. Recently, many of
these properties have been linked to the effect of carotenoids on intracellular
signaling cascades, thereby influencing gene expression and protein translation.
By blocking the translocation of nuclear factor kappaB to the nucleus,
carotenoids are able to interact with the nuclear factor kappaB pathway and thus
inhibit the downstream production of inflammatory cytokines, such as interleukin
8 or prostaglandin E2. Carotenoids can also block oxidative stress by interacting
with the nuclear factor erythroid 2-related factor 2 pathway, enhancing its
translocation into the nucleus, and activating phase II enzymes and antioxidants,
such as glutathione-S-transferases. In this review, which is organized into in
vitro, animal, and human investigations, we summarized current knowledge on
carotenoids and metabolites with respect to their ability to modulate
inflammatory and oxidative stress pathways and discuss potential dose-health
relations. Although many pathways involved in the bioactivity of carotenoids have
been revealed, future research should be directed toward dose-response relations
of carotenoids, their metabolites, and their effect on transcription factors and
metabolism.
PMID- 25134456
TI - Subdural and intracerebral hemorrhage caused by spontaneous bleeding in the
middle meningeal artery after coil embolization of a cerebral aneurysm.
AB - Nontraumatic acute subdural hemorrhage (SDH) with intracerebral hemorrhage (ICH)
is rare and is usually caused by severe bleeding from aneurysms or arteriovenous
fistulas. We encountered a very rare case of spontaneous bleeding from the middle
meningeal artery (MMA), which caused hemorrhage in the temporal lobe and subdural
space 2 weeks after coil embolization of an ipsilateral, unruptured internal
cerebral artery aneurysm in the cavernous portion. At onset, the distribution of
hematoma on a computed tomography scan led us to believe that the treated
intracavernous aneurysm could bleed into the intradural space. Emergency
craniotomy revealed that the dura of the middle fossa was intact except for the
point at the foramen spinosum where the exposed MMA was bleeding.
Retrospectively, angiography just before and after embolization of the aneurysm
did not show any aberrations in the MMA. Although the MMA usually courses on the
outer surface of the dura and is unlikely to rupture without an external force,
physicians should be aware that the MMA may bleed spontaneously and cause SDH and
ICH.
PMID- 25134457
TI - In vitro synergistic efficacy of conjugated linoleic acid, oleic acid, safflower
oil and taxol cytotoxicity on PC3 cells.
AB - The aim of this study was to determine in vitro synergistic efficacy of
conjugated linoleic acid (CLA), oleic acid (OLA), safflower oil and taxol (Tax)
cytotoxicity on human prostate cancer (PC3) cell line. To determine synergistic
efficacy of oil combinations, PC3 treated with different doses of compounds alone
and combined with 10 MUg/mL Tax. The MTT results indicated that OLA-Tax
combinations exhibited cytotoxicity against PC3 at doses of 30 nM+10 MUg-Tax, 15
nM+5 MUg-Tax and 7.5 nM+2.5 MUg-Tax. The treatment of OLA or Tax did not show
significant inhibition on PC3, while OLA-Tax combinations showed effective
cytotoxicity at treated doses. CLA-Tax combinations demonstrated the same effect
on PC3 as combined form with 45.72% versus the alone form as 74.51% viability.
Cytotoxic synergy between Tax, OLA and CLA shows enhanced cytotoxicity on PC3
which might be used in the therapy of prostate cancer.
PMID- 25134458
TI - Cytotoxicity of CD56-positive lymphocytes against autologous B-cell precursor
acute lymphoblastic leukemia cells.
AB - Precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) affects
hematopoietic development and therefore is associated with immune deficiencies
that can be further exacerbated by chemotherapy. It is unclear if and when
monoclonal antibodies (mAbs) that stimulate antibody-mediated cellular
cytotoxicity (ADCC) can be used for treatment because this depends on the
presence of functional effector cells. Here, we used flow cytometry to determine
that patient samples at diagnosis, post-induction and relapse contain detectable
numbers of CD56+ cells. We were able to selectively expand CD56+ immune effector
cells from bone marrow and peripheral blood samples at diagnosis and at various
stages of treatment by co-culture with artificial antigen-presenting K562 clone
9.mbIL-21 cells. Amplified CD56+CD3- cells had spontaneous and anti-B cell
activating factor receptor mAb-stimulated ADCC activity against allogeneic ALL
cells, which could be further enhanced by IL-15. Importantly, matched CD56+
effector cells also killed autologous ALL cells grown out from leukemia samples
of the same patient, through both spontaneous as well as antibody-dependent
cellular cytotoxicity. Since autologous cell therapy will not be complicated by
graft-versus-host disease, our results show that expanded CD56+ cells could be
applied for treatment of pre-B ALL without transplantation, or for purging of
bone marrow in the setting of autologous bone marrow transplants.
PMID- 25134460
TI - [Conjunctival amyloidosis].
AB - BACKGROUND: This article reports a case of primary localized conjunctival lambda
light-chain (AL) amyloidosis. METHODS: Case report. RESULTS: A 73-year-old woman
presented with a 1-year history of a painless growth in the conjunctiva of the
left eye. A yellow-salmon pink diffuse mass of tissue was identified in the
inferomedial bulbar conjunctiva and inferior fornix. An incisional biopsy was
performed. The histopathological and immunohistochemical examinations revealed
interstitial and vascular amyloid deposits of lambda light chains. The diagnosis
was amyloidosis of the conjunctiva. The systemic evaluation revealed normal
findings and systemic amyloidosis was excluded. Nevertheless, due to an
unexplained cardiac insufficiency and after consultation with the treating
hematologist a treatment with three cycles of systemic chemotherapy with
melphalan and prednisolone was initiated but 6 months later the conjunctival mass
in the inferior fornix showed persistence and complete excision was performed. At
16, 24 and 44 months of follow-up no evidence of recurrence was seen on clinical
examination. The magnetic resonance imaging (MRI) at 16 and 24 months of follow
up showed no associated cranial or orbital infiltration. CONCLUSION: Conjunctival
AL amyloidosis is a rare clinical entity. Because of the heterogeneity of
amyloidosis in clinical presentation, pattern of amyloid-related organ toxicity,
association with lymphoproliferative diseases and rate of disease progression,
identification of amyloid deposits is essential and systemic involvement has to
be excluded.
PMID- 25134462
TI - [Adjuvant anti-VEGF therapy in Coats' disease].
AB - BACKGROUND: Coats' disease is a non-hereditary acquired, usually unilateral eye
disorder that predominantly occurs in young males (1/100,000) with the onset of
symptoms generally appearing in the first two decades of life. Coats' disease is
characterized by telangiectatic changes, blood leaks from the defective vessels
with retinal exudation followed in advanced stages by retinal detachment. CASE
REPORT: A 14-year-old male patient presented in our department with gradual
visual loss in the right eye. Based on the clinical and diagnostic findings
Coats' disease was diagnosed. The exudative retinal detachment in the right eye
was initially treated with intravitreal bevacizumab injection (B-IVOM) followed
by cryocoagulation and combined with a second administration of B-IVOM 2 weeks
later. On the grounds of a persistent exudative retinal detachment a new round of
cryotherapy was conducted. We proceeded with laser coagulation of the residual
Coats areas and with three cycles of B-IVOM therapy. The subretinal and
intraretinal exudates regressed over several weeks so that the patient remained
symptom-free 22 months after therapy. At the last examination the visual acuity
was 0.8 in the right eye. CONCLUSION: The favorable development for our patient
demonstrates that adjuvant therapy with intravitreal anti-VEGF injections in
addition to laser and cryocoagulation in a case of advanced Coats' disease with
exudative retinal tissue damage could lead to the stabilization of the retinal
findings and to preservation of good visual acuity.
PMID- 25134463
TI - Stress-mediated tuning of developmental robustness and plasticity in flies.
AB - Organisms have to be sufficiently robust to environmental and genetic
perturbations, yet plastic enough to cope with stressful scenarios to which they
are not fully adapted. How this apparent conflict between robustness and
plasticity is resolved at the cellular and whole organism levels is not clear.
Here we review and discuss evidence in flies suggesting that the environment can
modulate the balance between robustness and plasticity. The outcomes of this
modulation can vary from mild sensitizations that are hardly noticeable, to overt
qualitative changes in phenotype. The effects could be at both the cellular and
whole organism levels and can include cellular de-/trans-differentiation
('Cellular reprogramming') and gross disfigurements such as homeotic
transformations ('Tissue/whole organism reprogramming'). When the stress is mild
enough, plastic changes in some processes may prevent drastic changes in more
robust traits such as cell identity and tissue integrity. However, when the
stress is sufficiently severe, this buffering may no longer be able to prevent
such overt changes, and the resulting phenotypic variability could be subjected
to selection and might assist survival at the population level. This article is
part of a Special Issue entitled: Stress as a fundamental theme in cell
plasticity.
PMID- 25134461
TI - [Corneal collagen cross-linking with riboflavin and ultraviolet-A light in
progressive keratoconus. Results after 10-year follow-up].
AB - PURPOSE: Riboflavin and ultraviolet-A induced cross-linking (CXL) is a promising
therapeutic option to halt the progression of keratoconus. The aim of the study
was to prove a long-term stabilizing effect of riboflavin and ultraviolet-A
induced collagen CXL in young and otherwise healthy patients with progressive
keratoconus and a corneal thickness of at least 400 MUm on average 10 years after
treatment. METHODS: Corneal CXL was performed after removing epithelial tissue by
instilling riboflavin 0.1% solution for 30 min before and during 30 min of
ultraviolet-A irradiation (370 nm, 3 mW/cm(2)). This long-term retrospective
study included 30 eyes of 20 patients with progressive keratoconus. Preoperative
and postoperative examinations on average 10 years after treatment included best
corrected visual acuity (BCVA), corneal topography (keratometry values KMAX, KMIN
and KApex), corneal thickness (CT) and if available endothelial cell density.
RESULTS: The mean preoperative age was 28 +/- 7 years (range 14-42 years), 4
patients were female (7 eyes) and 16 patients (23 eyes) were male.
Preoperatively, the mean K-value on the apex of keratoconus was 62 +/- 13.2 dpt
which showed a statistically significant reduction after 10 years to 55 +/- 8.1
dpt (p = 0.001). The mean KMAX (53 +/- 8.2 versus 49 +/- 6.6 dpt) and KMIN values
(48 +/- 5.5 vs. 45 +/- 5.1 dpt) also showed a statistically significant decrease
(p = 0.001). In comparison BCVA also showed a statistically significant
preoperative and postoperative difference (p = 0.005). There was a significant
improvement of BCVA by a mean of - 0.13 +/- 0.25 logMAR. The mean change in
corneal thickness at the 10-year follow up was 46 MUm (p = 0.001). Bias possibly
occurred because of a change of the measurement method from ultrasound pachymetry
to optical pachymetry with Oculus Pentacam(r). Neither corneal endothelium nor
deeper structures suffered any damage. Only two patients had continuous
progression of keratoconus and needed a reapplication of CXL. CONCLUSION: The
results of this study indicate that riboflavin and ultraviolet-A induced corneal
CXL is a promising therapeutic option for progressing keratoconus to obtain long
term stabilization. There was a sustained improvement of all K-values and BCVA 10
years after treatment and CXL is minimally invasive and easy to handle. Side
effects, such as endothelial damage did not occur.
PMID- 25134465
TI - A trapped-ion-based quantum byte with 10(-5) next-neighbour cross-talk.
AB - The addressing of a particular qubit within a quantum register is a key pre
requisite for scalable quantum computing. In general, executing a quantum gate
with a single qubit, or a subset of qubits, affects the quantum states of all
other qubits. This reduced fidelity of the whole-quantum register could prevent
the application of quantum error correction protocols and thus preclude
scalability. Here we demonstrate addressing of individual qubits within a quantum
byte (eight qubits) and measure the error induced in all non-addressed qubits
(cross-talk) associated with the application of single-qubit gates. The quantum
byte is implemented using microwave-driven hyperfine qubits of (171)Yb(+) ions
confined in a Paul trap augmented with a magnetic gradient field. The measured
cross-talk is on the order of 10(-5) and therefore below the threshold commonly
agreed sufficient to efficiently realize fault-tolerant quantum computing. Hence,
our results demonstrate how this threshold can be overcome with respect to cross
talk.
PMID- 25134459
TI - Combined STAT3 and BCR-ABL1 inhibition induces synthetic lethality in therapy
resistant chronic myeloid leukemia.
AB - Mutations in the BCR-ABL1 kinase domain are an established mechanism of tyrosine
kinase inhibitor (TKI) resistance in Philadelphia chromosome-positive leukemia,
but fail to explain many cases of clinical TKI failure. In contrast, it is
largely unknown why some patients fail TKI therapy despite continued suppression
of BCR-ABL1 kinase activity, a situation termed BCR-ABL1 kinase-independent TKI
resistance. Here, we identified activation of signal transducer and activator of
transcription 3 (STAT3) by extrinsic or intrinsic mechanisms as an essential
feature of BCR-ABL1 kinase-independent TKI resistance. By combining synthetic
chemistry, in vitro reporter assays, and molecular dynamics-guided rational
inhibitor design and high-throughput screening, we discovered BP-5-087, a potent
and selective STAT3 SH2 domain inhibitor that reduces STAT3 phosphorylation and
nuclear transactivation. Computational simulations, fluorescence polarization
assays and hydrogen-deuterium exchange assays establish direct engagement of
STAT3 by BP-5-087 and provide a high-resolution view of the STAT3 SH2 domain/BP-5
087 interface. In primary cells from chronic myeloid leukemia (CML) patients with
BCR-ABL1 kinase-independent TKI resistance, BP-5-087 (1.0 MUM) restored TKI
sensitivity to therapy-resistant CML progenitor cells, including leukemic stem
cells. Our findings implicate STAT3 as a critical signaling node in BCR-ABL1
kinase-independent TKI resistance, and suggest that BP-5-087 has clinical utility
for treating malignancies characterized by STAT3 activation.
PMID- 25134464
TI - beta-Arrestins regulate human cardiac fibroblast transformation and collagen
synthesis in adverse ventricular remodeling.
AB - Cardiac fibroblasts (CFs) produce and degrade the myocardial extracellular matrix
and are critical in maladaptive ventricular remodeling that can result in heart
failure (HF). beta-Arrestins are important signaling molecules involved in beta
adrenergic receptor (beta-AR) desensitization and can also mediate signaling in a
G protein-independent fashion. We hypothesize that beta-arrestins play an
important role in the regulation of adult human CF biology with regard to
myofibroblast transformation, increased collagen synthesis, and myocardial
fibrosis which are important in the development of HF. beta-Arrestin1 & 2
expression is significantly upregulated in adult human CF isolated from failing
left ventricles and beta-AR signaling is uncoupled with loss of beta-agonist
mediated inhibition of collagen synthesis versus normal control CF. Knockdown of
either beta-arrestin1 or 2 restored beta-AR signaling and beta-agonist mediated
inhibition of collagen synthesis. Overexpression of beta-arrestins in normal CF
led to a failing phenotype with increased baseline collagen synthesis, impaired
beta-AR signaling, and loss of beta-agonist-mediated inhibition of collagen
synthesis. beta-Arrestin knockdown in failing CF diminished TGF-beta stimulated
collagen synthesis and also inhibited ERK phosphorylation. Overexpression of beta
arrestins in normal CF increased basal ERK1/2 and Smad2/3 phosphorylation and
enhanced TGF-beta-stimulated collagen synthesis. This was prevented by pre
treatment with a MEK1/2 inhibitor. Enhanced beta-arrestin signaling appears to be
deleterious in CF by promoting a pro-fibrotic phenotype via uncoupling of beta-AR
signaling as well as potentiating ERK and Smad signaling. Targeted inhibition of
beta-arrestins in CF may represent a therapeutic strategy to prevent maladaptive
myocardial fibrosis.
PMID- 25134467
TI - Effect of backing films on the transdermal delivery of donepezil from patches.
AB - The aim of this work was to investigate the effect of backing films on
transdermal delivery of donepezil (DP) from patches. Three backing films,
CotranTM 9700, CotranTM 9701, and CotranTM 9726 were chosen as backing layers to
prepare transdermal patches containing DP. The transdermal penetration and
release amount of DP from each patch were evaluated by rabbit abdominal skin in
vitro. The partitioning experiments and attentuated total reflectance Fourier
transform infrared (ATR-FTIR) spectroscopy were performed to confirm the
existence of interaction between backing films and DP. Results showed that the
cumulative release amount of DP from patches with different backing films had the
same order of cumulative amount penetrated, i.e. CotranTM 9701 < CotranTM 9700 <
CotranTM 9726, which demonstrated that the permeation of DP was mainly limited by
release behavior. Partitioning experiments and ATR-FTIR study indicated that
CotranTM 9700 and CotranTM 9701 had interaction with DP by H bond formation which
decreased the release of drug from the patches. By contrast, CotranTM 9726 could
provide the highest flux of skin permeation of DP, because such interaction
between them was not found. Moreover, the parameters of backing films were found
to have relation to skin hydration, thus affecting the penetration behavior of DP
from patches. In conclusion, the effect of backing films on the flux of DP
permeation could be attributed to both the interaction of backing films and the
changes of skin hydration. Backing films could be a key factor in formulation
screening of DP patches.
PMID- 25134468
TI - Human stem cell-derived cardiomyocytes in cellular impedance assays: bringing
cardiotoxicity screening to the front line.
AB - Cardiovascular (CV) toxicity is a leading cause of drug attrition and withdrawal.
Introducing in vitro assays with higher throughput should permit earlier CV
hazard identification and enable medicinal chemists to design-out liabilities.
Heretofore, development of in vitro CV assays has been limited by the challenge
of replicating integrated cardiovascular physiology while achieving the
throughput and consistency required for screening. These challenges appear to be
met with a combination of human stem cell-derived cardiomyocytes (CM) which beat
spontaneously and monitoring the response with technology that can assess drug
induced changes in voltage dependent contraction such as cellular impedance which
has been validated with excellent predictivity for drug-induced arrhythmia and
contractility. Here, we review advances in cardiomyocyte impedance with emphasis
on stem cell-derived cardiomyocyte models for toxicity screening. Key
perspectives include: the electrical principles of impedance technology,
impedance detection of cardiomyocyte beating, beat parameter selection/analysis,
validation in toxicity and drug discovery, and future directions. As a
conclusion, an in vitro screening cascade is proffered using the downstream,
inclusive detection of CM impedance assays as a primary screen followed by
complementary CM assays chosen to enable mechanism-appropriate follow-up. The
combined approach will enhance testing for CV liabilities prior to traditional in
vivo models.
PMID- 25134466
TI - Brain-targeted delivery of docetaxel by glutathione-coated nanoparticles for
brain cancer.
AB - Gliomas are some of the most aggressive types of cancers but the blood-brain
barrier acts as an obstacle to therapeutic intervention in brain-related
diseases. The blood-brain barrier blocks the permeation of potentially toxic
compounds into neural tissue through the interactions of brain endothelial cells
with glial cells (astrocytes and pericytes) which induce the formation of tight
junctions in endothelial cells lining the blood capillaries. In the present
study, we characterize a glutathione-coated docetaxel-loaded PEG-PLGA
nanoparticle, show its in vitro drug release data along with cytotoxicity data in
C6 and RG2 cells, and investigate its trans-blood-brain barrier permeation
through the establishment of a Transwell cellular co-culture. We show that the
docetaxel-loaded nanoparticle's size enables its trans-blood-brain barrier
permeation; the nanoparticle exhibits a steady, sustained release of docetaxel;
the drug is able to induce cell death in glioma models; and the glutathione
coated nanoparticle is able to permeate through the Transwell in vitro blood
brain barrier model.
PMID- 25134469
TI - Using Bayesian hierarchical parameter estimation to assess the generalizability
of cognitive models of choice.
AB - To be useful, cognitive models with fitted parameters should show
generalizability across time and allow accurate predictions of future
observations. It has been proposed that hierarchical procedures yield better
estimates of model parameters than do nonhierarchical, independent approaches,
because the formers' estimates for individuals within a group can mutually inform
each other. Here, we examine Bayesian hierarchical approaches to evaluating model
generalizability in the context of two prominent models of risky choice
cumulative prospect theory (Tversky & Kahneman, 1992) and the transfer-of
attention-exchange model (Birnbaum & Chavez, 1997). Using empirical data of risky
choices collected for each individual at two time points, we compared the use of
hierarchical versus independent, nonhierarchical Bayesian estimation techniques
to assess two aspects of model generalizability: parameter stability (across
time) and predictive accuracy. The relative performance of hierarchical versus
independent estimation varied across the different measures of generalizability.
The hierarchical approach improved parameter stability (in terms of a lower
absolute discrepancy of parameter values across time) and predictive accuracy (in
terms of deviance; i.e., likelihood). With respect to test-retest correlations
and posterior predictive accuracy, however, the hierarchical approach did not
outperform the independent approach. Further analyses suggested that this was due
to strong correlations between some parameters within both models. Such
intercorrelations make it difficult to identify and interpret single parameters
and can induce high degrees of shrinkage in hierarchical models. Similar findings
may also occur in the context of other cognitive models of choice.
PMID- 25134471
TI - Susceptible to distraction: children lack top-down control over spatial attention
capture.
AB - Considerable evidence has indicated that adults can exert top-down control to
avoid distraction by salient-but-irrelevant stimuli. However, relatively little
research has explored how this ability develops across the lifespan. In the
present study, we therefore assessed how well children can control the capture of
spatial attention. Children (M age = 4.2 years) and adults (M age = 21.5 years)
searched for target "spaceships" of a specific color while trying to ignore
salient precues that either matched or mismatched the target spaceship color. The
results demonstrated that children are, in fact, more vulnerable to capture by
irrelevant stimuli than are adults, even after accounting for children's overall
cognitive slowing.
PMID- 25134472
TI - Letter from the editor.
PMID- 25134470
TI - Consciousness is not necessary for visual feature binding.
AB - When visual information enters the brain, it is relayed to different specialized
regions, processing features such as shape, color, or motion. And yet, in our
conscious experience of a colored, moving shape, all the different features seem
to be integrated into one unified percept. Therefore, it has been hypothesized
that consciousness and feature binding share an intimate relationship. To study
this relationship, we used a paradigm in which the behavioral effects of feature
binding can be measured. Using masks, we investigated whether spontaneous binding
between the orientation and location of a Gabor patch takes place when the Gabor
patch is processed consciously or unconsciously. The results of our study suggest
that orientation and location of a visually presented object are automatically
integrated, even when subjects are unaware of that object. We conclude that
binding and consciousness share a less intimate relationship than previously
hypothesized, since consciousness is not a necessary condition for binding to
occur.
PMID- 25134473
TI - Integrase Strand Transfer Inhibitors in HIV Therapy.
AB - HIV drug resistance has been one of the major obstacles to HIV eradication and
has contributed to the need for the constant development of new antiretroviral
drugs over the past 25 years. With the recent approval of dolutegravir for human
therapy by the U.S. Food and Drug Administration, health practitioners may soon
have access to three integrase strand transfer inhibitors to treat individuals
living with HIV. Here, we review the use of raltegravir, elvitegravir, and
dolutegravir for use in first- and second-line HIV treatment regimens and the
issue of HIV resistance against integrase inhibitors.
PMID- 25134475
TI - Cobicistat: a Novel Pharmacoenhancer for Co-Formulation with HIV Protease and
Integrase Inhibitors.
AB - Human immunodeficiency virus (HIV) therapy has evolved over the last 20 years
from mono-drug therapy given five times daily to regimens consisting of three or
four drugs combined in a single-tablet dosed once daily. To allow once-daily
administration, several drugs require pharmacokinetic boosting by a concomitantly
administered P-glycoprotein and cytochrome P450 inhibitor such as ritonavir. The
availability of cobicistat provides an alternative to ritonavir to those who are
intolerant to this drug, and the opportunity for co-formulated single-tablet
regimens consisting of tenofovir/emtricitabine, cobicistat and elvitegravir,
atazanavir or darunavir. The cobicistat/elvitegravir-based regimen is well
tolerated and patients achieved high rates of HIV RNA suppression in clinical
trials. Cobicistat inhibits renal tubular secretion of creatinine, resulting in
increased serum creatinine concentrations and reduced estimated glomerular
filtration rate, with a new set point reached after 4 weeks. Treatment limiting
renal toxicity with cobicistat/elvitegravir and tenofovir disoproxil fumarate is
infrequent and may be further reduced when cobicistat is co-formulated with
tenofovir alafenamide fumarate, a novel formation of tenofovir currently
undergoing clinical trials.
PMID- 25134474
TI - Ceftaroline fosamil: a brief clinical review.
AB - Ceftaroline is a novel cephalosporin with a favorable tolerability profile and
broad in vitro activity against many resistant Gram-positive and common Gram
negative organisms. Ceftaroline fosamil is the first cephalosporin to be approved
by the United States Food and Drug Administration (FDA) for the treatment of
adults with acute bacterial skin and soft tissue infections, including those
caused by methicillin-resistant Staphylococcus aureus (MRSA). It is also approved
by the FDA for the treatment of adults with community-acquired bacterial
pneumonia, including cases caused by Streptococcus pneumoniae (with or without
concurrent bacteremia), although there are no data at this time to support the
use of ceftaroline fosamil for the treatment of pneumonia caused by MRSA.
Ceftaroline fosamil is likewise approved by the European Commission for the
treatment of adults with complicated skin and soft tissue infections or community
acquired pneumonia. This review summarizes the pharmacokinetic and microbiologic
properties of ceftaroline, as well as the safety and efficacy data that led to
its approval by the FDA in 2010 and the European Commission in 2012. Future
directions to be addressed are also highlighted.
PMID- 25134476
TI - A Review of the Evidence for Using Bedaquiline (TMC207) to Treat Multi-Drug
Resistant Tuberculosis.
AB - Existing therapies for multi-drug resistant tuberculosis (MDR-TB) have
substantial limitations, in terms of their effectiveness, side-effect profile,
and complexity of administration. Bedaquiline is a novel diarylquinoline
antibiotic that has recently been investigated as an adjunct to existing
therapies for MDR-TB. Currently, limited clinical data are available to evaluate
the drug's safety and effectiveness. In two small randomized-controlled clinical
studies, bedaquiline given for 8 or 24 weeks has been shown to improve surrogate
microbiological markers of treatment response, but trials have not yet evaluated
its impact on clinical failure and relapse. Safety concerns include an increased
mortality in the bedaquiline arm of one study, an increased incidence of QT
segment prolongation on electrocardiogram, and hepatotoxicity. Until further
research data are available, the use of bedaquiline should be confined to
settings where carefully selected patients can be closely monitored.
PMID- 25134477
TI - Japanese B Encephalitis: An Overview of the Disease and Use of Chimerivax-JE as a
Preventative Vaccine.
AB - The Japanese encephalitis virus (JEV) is endemic in many countries in southern
Asia and the western Pacific Rim, with new spread to previously unrecognized
countries. It is an important cause of childhood neurological disease associated
with permanent neurological sequelae and death. Fortunately, JE is a vaccine
preventable disease. The ChimeriVaxTM-JE (Sanofi Pasteur, Lyon, France) is a live
attenuated chimeric vaccine derived from the live-attenuated yellow fever virus,
YF17D, which expresses the envelope proteins of the attenuated JEV vaccine
strain, SA14-14-2. It is a safe, well-tolerated vaccine that is highly
immunogenic in adults and children. The average geometric mean neutralizing
antibody titer (GMT) in adults is 1,392 and over 90% of adults remain
seroprotected 5 years after vaccination. In children and toddlers, more than 80%
remain seroprotected 2 years after primary vaccination and demonstrate a robust
and durable anamnestic response (>500-fold rise in GMT) with 99.1% seroprotection
rates 1 year after a booster vaccine dose. The ChimeriVaxTM-JE is effective in
children living in endemic regions where the vaccine could possibly be integrated
into existing childhood vaccination programs. ChimeriVaxTM-JE is also indicated
for travelers at risk of JE infection.
PMID- 25134479
TI - The problems with polio: toward eradication.
AB - The global health effort to eradicate poliomyelitis (polio) has encountered a
number of unforeseen and unpredictable challenges. This article provides a timely
review of progress made toward eradication, including the polio vaccines in use,
and explores the reasons for delays in eradication target dates. It provides an
overview of some of the remaining barriers to eradication and looks toward
overcoming these through the Polio Eradication and Endgame Strategic Plan.
PMID- 25134478
TI - The Role of Human Beta-Defensin-2 in Pseudomonas aeruginosa Pulmonary Infection
in Cystic Fibrosis Patients.
AB - Cystic fibrosis (CF) is the most common genetic disease affecting the Caucasian
population. Chronic Pseudomonas aeruginosa pulmonary infection is the major cause
of morbidity and mortality in CF patients. Human beta-defensin-2 (hBD-2) is an
inducible pulmonary antimicrobial peptide that exerts bacteriostatic activity in
a concentration-dependent manner. The decreased expression and compromised
function of hBD-2 contributes to the pathogenesis of P. aeruginosa infection in
the CF lung. The purpose of this review is to outline the significance of hBD-2
in P. aeruginosa chronic pulmonary infection in CF patients.
PMID- 25134480
TI - Is Community-Acquired Methicillin-Resistant Staphylococcus aureus Coverage Needed
for Cellulitis?
AB - Methicillin-resistant Staphylococcus aureus (MRSA) has become the dominant strain
of Staphylococcus aureus in many communities of the United States. As a result,
many clinicians are now empirically covering for this pathogen in the treatment
of various skin and soft-tissue infections. Should this practice apply to
cellulitis? In order to answer this question, we defined cellulitis and reviewed
the pathogenesis, microbiology, and current studies of inpatient and outpatient
antimicrobial therapy. The current evidence suggests empirical MRSA coverage for
community-acquired cellulitis may not be necessary in non-purulent (non
suppurative) forms of this infection. Most cases are non-purulent and not
amenable to culture although antibody studies indicate streptococci are the most
common etiologic agents. Current studies of antimicrobial therapy tend to agree
with this finding. Empirical beta-lactam therapy directed primarily at
streptococci appears sufficient for non-purulent cellulitis regardless of the
prevalence of MRSA in the community.
PMID- 25134482
TI - Comparative Incidence of Nephrotoxicity by Age Group among Adult Patients
Receiving Vancomycin.
AB - INTRODUCTION: Little is known regarding age-related risk of nephrotoxicity during
vancomycin therapy after the publication of the 2009 vancomycin consensus
guidelines for therapeutic drug monitoring. We sought to evaluate incidence and
risk factors for acute kidney injury in three age groups. METHODS: Matched cohort
study of patients receiving vancomycin, grouped by age: young adults (18-64
years), older adults (65-79 years) and very elderly (>=80 years), matched on
previously published risk factors for nephrotoxicity. Outcomes included
traditional vancomycin nephrotoxicity and Acute Kidney Injury Network-modified
definition of nephrotoxicity. RESULTS: The incidence of acute kidney injury was
34.1% vs. 34.1% vs. 31.8% in the young, older adults and very elderly groups,
respectively (p = 0.97). In the logistic regression model, after adjusting for
baseline risk factors, age was not a significant predictor of acute kidney
injury. Lower respiratory tract infection (adjusted odds ratio [aOR] 5.18; 95%
confidence interval [CI] 2.15-12.41) and duration of treatment (aOR 1.12; 95% CI
1.03-1.22) were found to be independently associated with outcome. CONCLUSION: No
differences in risk of acute kidney injury were identified between young, older,
and very elderly adults when adjusting for other risk factors. Further research
is required to identify strategies to optimize the safety of vancomycin in the
aging population.
PMID- 25134483
TI - Stable susceptibility to aminoglycosides in an age of low level, institutional
use.
AB - INTRODUCTION: The use of aminoglycosides has decreased dramatically over several
decades in the United States due to the introduction of safer Gram-negative
agents. This study was conducted to assess possibly changing aminoglycoside
susceptibility rates between 2006 and 2012 and in reference to 1992 use in the
context of aminoglycoside use volume. METHODS: Quarterly adult use of amikacin,
gentamicin and tobramycin were determined from the Medical University of South
Carolina Medical Center, Charleston, South Carolina, USA, pharmacy drug use
database and expressed as total aminoglycoside defined daily doses per 1,000
patient days for the years 1992 and 2006 through 2012. Annual susceptibility of
Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae, for the
years 1992, 2006, and 2008 through 2012 were retrieved from our hospital's
clinical microbiology database (duplicate isolates were excluded). Quarterly and
annualized aminoglycoside usage rates were compared to the other years of
interest. Likewise, susceptibility rates of the target organisms to each
aminoglycoside were also compared across the same timeframe. RESULTS: While total
use of aminoglycosides decreased slightly from 1992 to 2006, it increased by
about 40% between 2006 and 2008 and then stabilized. Changes in susceptibility
rates between 1992 and 2006 were all <=+/-9% with the exception of K. pneumoniae
susceptibility to amikacin (-17%). Changes in susceptibility from 1992 to 2012
were also all <=+/-9%. Tobramycin remained the most active versus P. aeruginosa
(% susceptible = 90), while amikacin remained most active versus E. coli and K.
pneumoniae (% susceptible = 98 and 98, respectively). CONCLUSION: With low level
use of aminoglycosides in our institution over the past 2 decades, the
susceptibility of key Gram-negative pathogens has remained relatively stable,
preserving these agents as potential alternative therapies as resistance arises
to other frequently used antibiotics.
PMID- 25134481
TI - Evaluation of Daptomycin Non-Susceptible Staphylococcus aureus for Stability,
Population Profiles, mprF Mutations, and Daptomycin Activity.
AB - INTRODUCTION: Despite studies examining daptomycin non-susceptible (DNS)
Staphylococcus aureus, examination of the stability and population profiles is
limited. The objective was to evaluate the stability, population profiles, and
daptomycin activity against DNS isolates. METHODS: The stability of 12
consecutive clinical DNS strains was evaluated by minimum inhibitory
concentration (MICs) and population analysis profiles before and after 5 days of
serial passage. Two pairs of DNS S. aureus having the same daptomycin MIC but
different daptomycin population profiles were evaluated via an in vitro
pharmacokinetic/pharmacodynamic (PK/PD) model of simulated endocardial
vegetations for 96 h against daptomycin 6 and 10 mg/kg/day. The sequence of mprF
was determined for these isolates before and after 96 h of daptomycin exposure in
the in vitro PK/PD model. RESULTS: Daptomycin MIC values were 2-4 mg/L (via
Microscan) for the 12 clinical isolates; 9 were confirmed DNS and 3 were within 1
tube dilution of Microscan (daptomycin MIC 1 mg/L). All were stable to serial
passage. There was variation in the isolates susceptibility to daptomycin on
population analysis (daptomycin population AUC 14.01-26.85). The killing patterns
of daptomycin 6 and 10 mg/kg/day differed between isolates with a left-shift and
right-shift population profile to daptomycin. Two strains developed additional
mprF mutations during daptomycin exposure in the in vitro PK/PD model resulting
in P314L, L826F, S337L and a novel Q326Stop mutation. CONCLUSIONS: The collection
of DNS isolates was stable and displayed variation in susceptibility to
daptomycin on population profile. Further research examining this clinical
relevance is warranted.
PMID- 25134484
TI - Amikacin pharmacokinetics during continuous veno-venous hemodialysis.
AB - INTRODUCTION: Little is known about the pharmacokinetics of amikacin during
continuous renal replacement therapy. METHODS: This prospective observational
study included patients admitted to an academic medical center who received
amikacin therapy while on continuous veno-venous hemodialysis (CVVHD) and had at
least two serum sample concentrations measured after first-dose administration.
First-order pharmacokinetic parameters, patient characteristics, and CVVHD
parameters were recorded. RESULTS: Fifteen patients were included in the
analysis. The median (interquartile range) dose of amikacin and dialysate flow
rate, based on adjusted body weight, were 14.1 mg/kg (11.7-17.3 mg/kg) and 23.9
mL/kg/h (19.0-29.5 mL/kg/h), respectively. This corresponded with a median C max
of 28.5 MUg/mL (20.9-39.0 MUg/mL). There was a significant correlation between
clearance and dialytic dose (for every 1 L/h increase in dialysate flow rate,
clearance rate increased by 23.6 mL/min [95% confidence interval 1.7-45.4 mL/min;
P = 0.037]). CONCLUSION: The results of this study suggest that amikacin dose and
interval should be individualized for each patient on CVVHD based on first-dose
pharmacokinetic assessment.
PMID- 25134485
TI - Erratum to: Low Specificity of a Malaria Rapid Diagnostic Test During an
Integrated Community Case Management Trial.
PMID- 25134486
TI - Divergent total synthesis of 1,6,8a-tri-epi-castanospermine and 1-deoxy-6,8a-di
epi-castanospermine from substituted azetidin-2-one (beta-lactam), involving a
cascade sequence of reactions as a key step.
AB - A divergent, short, and novel total synthesis of 1,6,8a-tri-epi-castanospermine
(7) and 1-deoxy-6,8a-di-epi-castanospermine (8) has been developed via a common
precursor, 15, obtained from D-mannitol derived beta-lactam. The key step
involves a one pot cascade sequence of trimethyl sulfoxonium ylide based
cyclization of epoxy sulfonamide 14via epoxide ring opening, one carbon
homologation followed by intramolecular cyclization.
PMID- 25134487
TI - Computational mitral valve evaluation and potential clinical applications.
AB - The mitral valve (MV) apparatus consists of the two asymmetric leaflets, the
saddle-shaped annulus, the chordae tendineae, and the papillary muscles. MV
function over the cardiac cycle involves complex interaction between the MV
apparatus components for efficient blood circulation. Common diseases of the MV
include valvular stenosis, regurgitation, and prolapse. MV repair is the most
popular and most reliable surgical treatment for early MV pathology. One of the
unsolved problems in MV repair is to predict the optimal repair strategy for each
patient. Although experimental studies have provided valuable information to
improve repair techniques, computational simulations are increasingly playing an
important role in understanding the complex MV dynamics, particularly with the
availability of patient-specific real-time imaging modalities. This work presents
a review of computational simulation studies of MV function employing finite
element structural analysis and fluid-structure interaction approach reported in
the literature to date. More recent studies towards potential applications of
computational simulation approaches in the assessment of valvular repair
techniques and potential pre-surgical planning of repair strategies are also
discussed. It is anticipated that further advancements in computational
techniques combined with the next generations of clinical imaging modalities will
enable physiologically more realistic simulations. Such advancement in imaging
and computation will allow for patient-specific, disease-specific, and case
specific MV evaluation and virtual prediction of MV repair.
PMID- 25134488
TI - Hypothalamic pituitary dysfunction amongst nasopharyngeal cancer survivors.
AB - PURPOSE: Radiation fields for nasopharyngeal cancer (NPC) include the base of
skull, which places the hypothalamus and pituitary at risk of damage. We aimed to
establish the prevalence, pattern and severity of hypothalamic pituitary (HP)
dysfunction amongst NPC survivors. METHODS: We studied 50 patients (31 males)
with mean age 57 +/- 12.2 years who had treatment for NPC between 3 and 21 years
(median 8 years) without pre-existing HP disorder from other causes. All patients
had a baseline cortisol, fT4, TSH, LH, FSH, oestradiol/testosterone, prolactin
and renal function. All patients underwent dynamic testing with insulin tolerance
test to assess the somatotroph and corticotroph axes. Baseline blood measurements
were used to assess thyrotroph, gonadotroph and lactotroph function. RESULTS:
Hypopituitarism was present in 82% of patients, 30% single axis, 28% two axes,
18% three axes and 6% four axes deficiencies. Somatotroph deficiency was most
common (78%) while corticotroph, gonadotroph and thyrotroph deficiencies were
noted in 40% (4 complete/16 partial), 22 and 4% of the patients respectively.
Hyperprolactinaemia was present in 30% of patients. The development of HP
dysfunction was significantly associated with the time elapsed from irradiation,
OR 2.5 (1.2, 5.3), p = 0.02, for every 2 years post treatment. The use of
concurrent chemo-irradiation (CCRT) compared to those who had radiotherapy alone
was also significantly associated with HP dysfunction, OR 14.5 (2.4, 87.7), p <
0.01. CONCLUSION: Despite low awareness and detection rates, HP dysfunction post
NPC irradiation is common. Use of CCRT may augment time related pituitary damage.
As these endocrinopathies result in significant morbidity and mortality we
recommend periodic assessment of pituitary function amongst NPC survivors.
PMID- 25134489
TI - A novel AMPK activator reduces glucose uptake and inhibits tumor progression in a
mouse xenograft model of colorectal cancer.
AB - The anticancer activity of a novel pure 1,4-Diaryl-2-azetidinone (1), endowed
with a higher solubility than the well known Combretastatin A4, is tested in
mice. We previously reported that Compound (1) showed specific antiproliferative
activity against duodenal and colon cancer cells, inducing activation of AMP
activated protein kinase and apoptosis. Here we estimate that the maximum
tolerated dose in a mouse model is 40 mg/kg; the drug is well tolerated both in
single dose and in repeated administration schedules. The drug displays a
significant antitumor activity and a tumor growth delay when administered at the
MTD both in single and fractionated i.v. administration in a mouse xenograft
model of colorectal cancer. Arrest of tumor growth and relapse after drug
suspension are parallel to modification in glucose demand as shown by PET studies
with [(18)F] FDG. These data strongly support Compound (1) as a promising
molecule for in vivo treatment of colorectal cancer.
PMID- 25134491
TI - In situ SERS detection of emulsifiers at lipid interfaces using label-free
amphiphilic gold nanoparticles.
AB - Herein, we fabricated amphiphilic gold nanoparticles (GNPs) that can self
assemble at oil-water interfaces. We applied those GNPs for in situ SERS
detection of emulsifier molecules within the interfacial region of oil in water
(O/W) emulsion systems.
PMID- 25134490
TI - Mechanisms of beta-lactam antimicrobial resistance and epidemiology of major
community- and healthcare-associated multidrug-resistant bacteria.
AB - Alexander Fleming's discovery of penicillin heralded an age of antibiotic
development and healthcare advances that are premised on the ability to prevent
and treat bacterial infections both safely and effectively. The resultant
evolution of antimicrobial resistant mechanisms and spread of bacteria bearing
these genetic determinants of resistance are acknowledged to be one of the major
public health challenges globally, and threatens to unravel the gains of the past
decades. We describe the major mechanisms of resistance to beta-lactam
antibiotics - the most widely used and effective antibiotics currently - in both
Gram-positive and Gram-negative bacteria, and also briefly detail the existing
and emergent pharmacological strategies to overcome such resistance. The global
epidemiology of the four major types of bacteria that are responsible for the
bulk of antimicrobial-resistant infections in the healthcare setting -
methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci,
Enterobactericeae, and Acinetobacter baumannii - are also briefly described.
PMID- 25134492
TI - Analysis of spontaneous pneumothorax in the city of Cuneo: environmental
correlations with meteorological and air pollutant variables.
AB - BACKGROUND AND PURPOSE: Primary spontaneous pneumothorax (PSP) tends to cluster.
Previous studies have found a correlation between PSP and atmospheric pressure
variations or thunderstorms. We conducted this study to analyze the PSP
correlations with meteorological variables and the concentrations of air
pollutants in the city of Cuneo in Italy (IT). METHODS: We evaluated
prospectively 451 consecutive PSP patients treated between 2004 and 2010. For
each day within the period analyzed, the meteorological parameters and pollutants
data were recorded. Statistical analyses on PSP were done for distribution
characteristics, spectral autocorrelation, and spectral analysis. Multivariate
regression analyses were performed using artificial neural networks. RESULTS:
Analysis of annual, seasonal, and monthly distributions showed no significant
correlation between PSP and the time series. The spectral analysis showed that
PSP events were not random. Correlations between meteorological and environmental
variables confirmed that PSP was significantly more likely to occur on warm windy
days with high atmospheric pressure and high mean nitrogen dioxide concentration.
CONCLUSIONS: Meteorological parameters and atmospheric pollutants might explain
the cluster onset of PSP.
PMID- 25134493
TI - Ocular Pharmacokinetics of a Novel Loteprednol Etabonate 0.4% Ophthalmic
Formulation.
AB - INTRODUCTION: Topical ophthalmic formulations of corticosteroids are commonly
used to treat a variety of ocular diseases and conditions that have an
inflammatory component. The purpose of this study was to evaluate the effect of
the mucus-penetrating particle (MPP) technology on the pharmacokinetic profile of
loteprednol etabonate in the ocular tissues of rabbits. METHODS: Forty-eight New
Zealand White rabbits were randomly assigned to two groups (n = 3 rabbits or 6
eyes per time point) and treated with either the novel loteprednol etabonate MPP
suspension formulation, 0.4% (LE-MPP 0.4%), or the commercial Lotemax((r))-brand
loteprednol etabonate ophthalmic suspension, 0.5% (Lotemax 0.5%) (Bausch & Lomb
Incorporated, Inc., Rochester, NY, USA). Samples of aqueous humor, various ocular
tissues, and plasma were collected from animals over a 12-h period after a single
dose of the test articles. Loteprednol etabonate concentrations were assayed
using liquid chromatography-tandem mass spectrometry (LC/MS/MS). RESULTS:
Loteprednol etabonate was rapidly absorbed into ocular tissues following
administration of either formulation. A higher ocular exposure was achieved using
LE-MPP 0.4%, with peak concentrations of approximately threefold higher in ocular
tissues and the aqueous humor than Lotemax 0.5%. CONCLUSIONS: Administration of
LE-MPP 0.4% improved loteprednol etabonate pharmacokinetic profile in ocular
tissues of rabbits. The results of this study support the premise that the MPP
technology can be used to enhance ocular exposure for topically applied
therapeutic agents. Further studies to assess the clinical efficacy and safety of
the LE-MPP formulation are warranted.
PMID- 25134494
TI - Historical Review and Update of Surgical Treatment for Corneal Endothelial
Diseases.
AB - The cornea remains in a state of deturgescence, maintained by endothelial cell
Na+/K+ ATPase and by tight junctions between endothelial cells that limit
entrance of fluid into the stroma. Fuchs' endothelial corneal dystrophy (FECD)
was initially described by Fuchs in 1910 as a combination of epithelial and
stromal edema in older patients. It manifests as bilateral, albeit asymmetric,
central corneal guttae, corneal edema, and reduced vision. When edema is severe,
the corneal epithelium can detach from its basement membrane, creating painful
bullae on the anterior surface of the cornea. The course of this dystrophy can be
further accelerated after intraocular surgery, specifically cataract extraction.
Pseudophakic bullous keratopathy (PBK) is endothelial cell loss caused by surgery
in the anterior chamber. If the corneal endothelium is damaged during surgery,
the same spectrum of symptoms as found in FECD can develop. In the nineteenth
century, penetrating keratoplasty was the only surgical procedure available for
isolated endothelial disease. In the 1960s, Dr. Jose Barraquer described a method
of endothelial keratoplasty using an anterior approach via laser-assisted in situ
keratomileusis (LASIK) flap. In 1999, Melles and colleague described their
technique of posterior lamellar keratoplasty. Later, Melles et al. started to
change host dissection using simple "descemetorhexis" in a procedure known as
Descemet's stripping endothelial keratoplasty. Following the widespread adoption
of Descemet's stripping automated endothelial keratoplasty, the Melles group
revisited selective Descemet's membrane transplantation and reported the results
of a new procedure, Descemet's membrane endothelial keratoplasty (DMEK).
Recently, some eye banks have experimented with the preparation of
DMEK/Descemet's membrane automated endothelial keratoplasty donor tissue that may
help the surgeon avoid the risk of tissue loss during the stromal separation
step. Recently, the authors described a new bimanual technique for insertion and
positioning of endothelium-Descemet membrane grafts in DMEK.
PMID- 25134495
TI - Review of Systemic Immunosuppression for Autoimmune Uveitis.
AB - The purpose of this review is to comprehensively examine the various therapeutic
agents available to treat autoimmune eye disease, their indications, clinical
safety and recent developments. The stepladder approach is reviewed, including
corticosteroid administration of various forms, classic immunomodulators, and
newer biologic response modifiers. The authors present that corticosteroid
monotherapy is almost never curative and carries significant side effects, while
immunomodulatory therapy, when used appropriately as way to induce steroid-free
remission, carries far less risk of causing long-term complications and provides
greater potential of altering the immune system to induce a durable remission.
PMID- 25134496
TI - Antioxidants Improve the Viability of Stored Adult Retinal Pigment Epithelial-19
Cultures.
AB - INTRODUCTION: There is increasing evidence that retinal pigment epithelium (RPE)
can be used to treat age-related macular degeneration, one of the leading causes
of blindness worldwide. However, the best way to store RPE to enable worldwide
distribution is unknown. We investigated the effects of supplementing our
previously published storage method with seven additives, attempting to improve
the number of viable adult retinal pigment epithelial (ARPE)-19 cells after
storage. MATERIALS AND METHODS: ARPE-19 cells were cultured on multiwell plates
before being stored for 1 week at 16 degrees C. Unsupplemented Minimal Essential
Medium (MEM) (control) and a total of seven individual additives (DADLE ([D
Ala(2), D-Leu(5)]-encephalin), capsazepine, docosahexaenoic acid (DHA),
resveratrol, quercetin, simvastatin and sulforaphane) at three to four
concentrations in MEM were tested. The individual effect of each additive on cell
viability was analyzed with a microplate fluorometer. Cell phenotype was
investigated by both microplate fluorometer and epifluorescence microscopy, and
morphology by scanning electron microscopy. RESULTS: Supplementation of the
storage medium with DADLE, capsazepine, DHA or resveratrol significantly
increased the number of viable cells by 86.1% +/- 41.9%, 67.9% +/- 24.7%, 36.5%
+/- 10.3% and 21.1% +/- 6.4%, respectively, compared to cells stored in
unsupplemented MEM. DHA and resveratrol significantly reduced caspase-3
expression, while expression of RPE65 was maintained across groups. CONCLUSION:
The number of viable ARPE-19 cells can be increased by the addition of DADLE,
capsazepine, DHA or resveratrol to the storage medium without perturbing
apoptosis or differentiation.
PMID- 25134497
TI - A randomized controlled longitudinal naturalistic trial testing the effects of
automatic self transcending meditation on heart rate variability in late life
depression: study protocol.
AB - BACKGROUND: The prevalence and socioeconomic cost of late life depression (LLD)
is on the rise, while the response rate to antidepressant trials remains poor.
Various mind-body therapies are being embraced by patients as they are considered
safe and potentially effective, yet little is known regarding the effectiveness
of such therapies to improve LLD symptoms. Among the mind-body therapies
currently in practice, the results of our pilot study have shown that a
particular meditation technique called Sahaj Samadhi Meditation, which belongs to
the category of meditation termed automatic self-transcending meditation (ASTM)
may have some promise in improving cardiovascular autonomic disturbances
associated with LLD as well as ameliorating symptoms of depression and anxiety.
METHODS/DESIGN: Patients between the ages of 60 and 85 with LLD will be
randomized either to ASTM plus treatment as usual (TAU) or TAU alone to assess
changes in cardiovascular autonomic parameters, neuropsychological symptoms of
depression and anxiety as well as quality of life. The instructional phase of the
intervention consists of 4 consecutive days of meditation training, after which
participants are encouraged to meditate twice daily for twenty minutes each time
at home. The intervention also includes once weekly follow up sessions for the
subsequent 11 weeks. The planned study has one and a half year recruitment
period. Participants will be assessed at baseline and at 4, 8, 12 and 24 weeks
post intervention. DISCUSSION: This study should provide a unique data source
from a randomized, controlled, longitudinal trial to investigate the effects of a
form of ASTM on cardiovascular autonomic and neuropsychological health in LLD.
TRIAL REGISTRATION: Clinicaltrials.gov NCT02149810, date registered: 05/28/2014.
PMID- 25134498
TI - Hurler syndrome: orofacial, dental, and skeletal findings of a case.
AB - Hurler syndrome is a disorder of mucopolysaccharide metabolism caused due to
inherited deficiencies of lysosomal alpha-l-iduronidase activity. We present a
case of a 15-year-old male patient presenting with clinical and laboratory
characteristics of the syndrome. A rare combination of skeletal, ophthalmologic,
and dental findings was observed in this patient. Mucopolysaccharides excretion
spot test of urine was positive and an assay of alpha-l-iduronidase enzyme was
deficient, confirming the clinical diagnosis of Hurler syndrome.
PMID- 25134499
TI - Evidence for a role of 5-HT2C receptors in the motor aspects of performance, but
not the efficacy of food reinforcers, in a progressive ratio schedule.
AB - RATIONALE: 5-Hydroxytryptamine2C (5-HT2C) receptor agonists reduce the breakpoint
in progressive ratio schedules of reinforcement, an effect that has been
attributed to a decrease of the efficacy of positive reinforcers. However, a
reduction of the breakpoint may also reflect motor impairment. Mathematical
models can help to differentiate between these processes. OBJECTIVE: The effects
of the 5-HT2C receptor agonist Ro-600175 ((alphaS)-6-chloro-5-fluoro-alpha-methyl
1H-indole-1-ethanamine) and the non-selective 5-HT receptor agonist 1-(m
chlorophenyl)piperazine (mCPP) on rats' performance on a progressive ratio
schedule maintained by food pellet reinforcers were assessed using a model
derived from Killeen's Behav Brain Sci 17:105-172, 1994 general theory of
schedule-controlled behaviour, 'mathematical principles of reinforcement'.
METHOD: Rats were trained under the progressive ratio schedule, and running and
overall response rates in successive ratios were analysed using the model. The
effects of the agonists on estimates of the model's parameters, and the
sensitivity of these effects to selective antagonists, were examined. RESULTS: Ro
600175 and mCPP reduced the breakpoint. Neither agonist significantly affected a
(the parameter expressing incentive value), but both agonists increased delta
(the parameter expressing minimum response time). The effects of both agonists
could be attenuated by the selective 5-HT2C receptor antagonist SB-242084 (6
chloro-5-methyl-N-{6-[(2-methylpyridin-3-yl)oxy]pyridin-3-yl}indoline-1
carboxamide). The effect of mCPP was not altered by isamoltane, a selective 5
HT1B receptor antagonist, or MDL-100907 ((+/-)2,3-dimethoxyphenyl-1-(2-(4
piperidine)methanol)), a selective 5-HT2A receptor antagonist. CONCLUSIONS: The
results are consistent with the hypothesis that the effect of the 5-HT2C receptor
agonists on progressive ratio schedule performance is mediated by an impairment
of motor capacity rather than by a reduction of the incentive value of the food
reinforcer.
PMID- 25134501
TI - Effects of mixing alcohol with energy drink on objective and subjective
intoxication: results from a Dutch on-premise study.
AB - BACKGROUND: The purpose of this on-premise study was to determine if alcohol
mixed with energy drink (AMED) consumption masks the subjective feelings of
intoxication when compared to consuming alcohol only. METHODS: The study was
conducted on five nights in the city center of Utrecht. N = 997 people leaving
bars were interviewed about their alcohol consumption with and without energy
drinks, for that particular evening and for other occasions. People reporting
drug and medication use were excluded (N = 84). Subjective intoxication was rated
on a 10-point scale. Objective intoxication (breath alcohol concentration, BrAC)
was determined with a breath alcohol test. Three groups were identified: (1) the
AMED-tonight group (N = 185, 20.2 %), (2) the AMED-other-nights group (N = 246,
27.1 %), and (3) the no-AMED group (N = 482, 52.7 %). RESULTS: Objective
intoxication (BrAC) did not significantly differ (p = 0.94) between the AMED
tonight group (0.074 % +/- 0.05), AMED-other-nights group (0.073 % +/- 0.05), and
the no-AMED group (0.074 % +/- 0.05). In line, subjective intoxication was not
significantly different (p = 0.96) between the AMED-tonight group (4.5 +/- 2.2),
AMED-other-nights group (4.6 +/- 2.3), and no-AMED group (4.6 +/- 2.2). Within
subjects comparisons revealed no significant differences in total alcohol
consumption between AMED occasions and alcohol only occasions. Regression
analyses showed that "gender" (beta = 0.078, p = 0.016), "time of testing" (beta
= 0.085, p = 0.009,) and "BrAC" (beta = 0.574, p = 0.0001) together explained
37.7 % of variance of subjective intoxication scores (Cohen's f (2) = 0.605).
Whether or not subjects consumed energy drinks did not predict subjective
intoxication scores. CONCLUSION: The data suggests that mixing alcohol with
energy drink does not mask subjective intoxication.
PMID- 25134500
TI - Differential effects of dopamine D1 and D 2/3 receptor antagonism on motor
responses.
AB - RATIONALE: The zebrafish dopaminergic system is thought to be evolutionarily
conserved and may be amenable to pharmacological manipulation using drugs
developed for mammalian receptors. However, only few studies have examined the
role of specific receptor subtypes in behaviour of adult zebrafish. OBJECTIVES:
The objectives of this study are to determine the translational relevance of the
zebrafish and examine the psychopharmacology of specific dopamine receptors in
this species. METHODS: Using a behavioural pharmacological approach, we examine
the effect of D1 and D2/3 receptor antagonisms on motor patterns of adult
zebrafish during acute drug exposure and withdrawal. RESULTS: Acute exposure to
SCH-23390 (D1 receptor antagonist) decreased total distance travelled in a dose
dependent manner. Exposure to amisulpride (D2/3 receptor antagonist) induced a
biphasic dose-response in total distance travelled and in angular velocity. The
results provide support for the existence of structurally and functionally
conserved postsynaptic D1 and D2 receptors, as well as presynaptic D2
autoreceptors in the zebrafish brain. The behavioural effects of the employed
antagonists did not persist following 30 min of withdrawal. CONCLUSION: The
results suggest that zebrafish, a cheaper and simpler model organism compared to
the rat and the mouse, may be an efficient translationally relevant tool for the
analysis of the psychopharmacology of receptors of the vertebrate dopaminergic
system.
PMID- 25134503
TI - [Editorial: Nursing and health care reform].
PMID- 25134502
TI - Behavioral effects of glucocorticoids during the first exposures to the forced
swim stress.
AB - RATIONALE: Glucocorticoids facilitate coping with stress, but their high levels
have been also implicated in mood disorders. Due to this duality, the role of
glucocorticoid signaling in the development of the first episodes of stress
induced depression remains unclear. OBJECTIVES: To address this issue, effects of
the glucocorticoid signal modulation on depressive-like behavior during pretest
and test Porsolt swim sessions were examined. METHODS: Metyrapone (MET; 150
mg/kg, i.p.) was injected 3 h before pretest to block stress-induced increase in
corticosterone levels. Dexamethasone (DEX; 0.2 mg/kg, s.c.) was applied to MET
treated rats 1 h before both pretest and test sessions. In addition to behavior
during these sessions, glucocorticoid receptor (GR) expression was analyzed by
immunohistochemistry 2 h after the second swim. RESULTS: In pretest, MET-treated
rats exhibited increased latency to immobility and shortened immobility. DEX
reversed the behavioral effects of MET in the pretest. In the test, animals from
MET + DEX group unexpectedly exhibited an antidepressant-like behavior. Swim
stress increased GR expression in the frontal cortex irrespective of the
pharmacological treatment. A significant elevation in GR expression was found in
the prefrontal cortex (PFC) of stressed MET + DEX-treated rats and in the PFC of
unstressed rats 6 h after injection of DEX alone. CONCLUSION: The data suggest
that the increase in glucocorticoid levels under swim stress during pretest
directly contributes to the development of the immobility response. Transition of
DEX effect from prodepressant in the pretest to an antidepressant in the test was
associated with the elevation in the PFC GR expression.
PMID- 25134505
TI - [Mission woman: a survey on the perception of the "Service of Welcome and
Listening" offered in the Emergency Department at the San Camillo Hospital in
Rome by women victims of violence].
AB - INTRODUCTION: The project Mission Woman was set up to describe how the service
offered by the Emergency Department of the Hospital San Camillo-Forlanini in Rome
was perceived by women victims ( or supposed to be) of violence. The objective of
this investigation is to frame clients' perception about the service offered by
staff in terms of sensitivity, recognition and management of the issue. The
access to the Emergency Room is the first contact of the client with a helping
relationship which goes beyond the simple provision of medical care. METHODS: A
questionnaire devised for the purpose was filled in by women who have asked for
help to the Service "Door Woman" . The Service "Door Woman", set up in 2009,
aimed to welcome and listen women victims of violence with the collaboration of
different operators in the emergency department: nurses, doctors, psychologists
and social workers. The project developed within the Hospital S. Camillo
Forlanini is managed by both professionals of the Emergency Department together
with the Charity "Be Free". The service is open 24/7, all year, the clients could
be women or children and could receive assistance or medical, nursing,
psychosocial and legal counselling. The triage nurses are those who through their
expertise could first identify the victims of violence and to introduce them in
the path. CONCLUSION: Despite the level of injuries, who access to the Emergency
Room for single or repeated events of violence, may have decided to claim in
court and not hide seeking.. The research aims to understand what are the
theoretical and practical deficiencies of staff in the management of a issue
which is not only medical but also social and legal, as well as structural and
organizational weaknesses of the service.
PMID- 25134504
TI - [Waiting time between acute event and rehabilitation: continuity of nursing care
and rehabilitation. Analysis and suggestions for a Service of Protected
Discharge].
AB - INTRODUCTION: In recent years, in Italy, population lengthening of life leads to
an higher number of individuals with chronic diseases (Osservatorio, 2010). The
hospital which deals with the acute phase of diseases needs to be integrated with
primary care. This connection is particularly important for the treatment, care
and rehabilitation of patient, as well as a general need for more health and
social care integrated tools. OBJECTIVE: At the San Gerardo Hospital in Monza, in
the context of the patient's post-acute rehabilitation, we analyze the phase
between discharge from hospital and the expected date of hospitalization in
facilities providing rehabilitation. The aim of this observational descriptive
study is to determine the distribution of days of waiting. Furthermore, several
different approach are analysed (i.e. Integrated Home Care) in order to reduce
unnecessary days hospitalization and a more intelligent and cost effective use of
resources The research question are the follow, to quantify waiting time between
discharge and hospitalization in the rehabilitation facility and to ascertain if
patients are sent to the correct facility. RESULT: 1083 individuals were taken
into account, of those 55% (N=652) were discharged from the hospital later. This
leads to a 4505 days of inappropriate hospitalization. CONCLUSION: Although the
use of home care could be beneficial to the hospital, this can be used only for
tiny part of the patients and it is not cost effective. A possible solution can
be set up a number of low cost bed entirely managed by nurses due to the low
level of intensity care.
PMID- 25134506
TI - [Profiles and evaluation process: what integration? Experience of the Local
Health Agency TO2 of Turin].
AB - INTRODUCTION: The Service of Health Professions of this facility (TO2 of Turin)
aimed during the 2010 to devise/develop a new evaluation tool for the new
employees , trying to fit them with the profiles set up the previous year.
METHODS: The conceptual model of reference for the construction of working drafts
of the grids was inspired by the special insert edition of "L'infermiere" in
2007, a literature review was carried out and a number of internal meeting within
6 of the Service of health Professions were set up. A working group were set up -
93 people - as well as indicators were developed to monitor and implementation of
the instruments. Once the drafts of the standard tools were made, working groups
started to improve the tools provided under the supervision of a tutor. Finally
half way through an evaluation was carried out using a questionnaire. CONCLUSION:
The new template leads a number of problems which were later sorted out also with
the support of tutors.
PMID- 25134507
TI - [Scale Mosaic: definition and testing of a tool for assessing the risk of falling
and the care planning during hospitalization].
AB - INTRODUCTION: in year 2008 the Ausl of Ravenna had a small number of patients at
risk among the patients fallen, and among the patients evaluated with risk for
fall. This could be due to the rating scale used (Conley) that does not recognize
the risk factors "drug therapy" and "conditions clinical care". OBJECTIVES: to
experiment a rating scale (Mosaic), to evaluate the performance indicators
compared to the scales Conley, Fall Risk Assessment Scoring System (FRASS),
Stratity; evaluate the effectiveness of actions taken to manage the risk;
Operators remain vigilant about the risk falls. METHODOLOGY: using the scale
Mosaic for patients admitted in 16 Hospital Units for two-months. Performance
indicators: sensitivity, specificity, positive predictive value and negative.
Studies considered for comparison: Hospital (AO) Bologna for Conley, AO Bologna
and AO Niguarda Ca Granda Milan for Stratify, AO Bergamo for FRASS. RESULTS: were
analyzed 1474 tabs. Males are 848 (57.5%) and females 626 (43.5%), the average
age is 70.8 years. Of these 42 patients have fallen (2.8%), including 25 males
and 17 females and the average age is 72.2. Are not at risk 426 (29%) patients
and at risk 1048 (71%) patients. In other assessments the patients at risk was
31% in AUSL Ravenna, 59% (Conley) and 13% (Stratify) in AO Bologna and 41.5%
(FRASS) in AO Bergamo. The scale Mosaic has a sensitivity of 0.98 (Conley,
Stratify and FRASS amounted to 0.69, to 0.20, to 0.50), a specificity of 0.30
(Conley, Stratify and FRASS amounted to 0.41, 0.87, 0.59.) The patients fallen
are at risk in 41 cases (97%) and of these 24 low-risk. The most frequent risk
factors are: "mobility and gait" (1209 items), "drug therapy" (850 items) ,
"conditions clinical care" (841 items). Planned actions have an average of 2.2 in
patients fallen, of 3.5 in low-risk patients and of 4.48 in patients at high
risk. Compared with the previous year shows a decrease of 14 falls and an
increase in the level of outcome "no one" (from 61% to 73.5%). DISCUSSION: the
greater number of falls occur among low-risk patients, the average number of
shares increases with increasing levels of risk and decreases in the patients
fallen. Patients are at increased risk and therefore, in the hospital, it is
essential to evaluate the factors drug therapy and conditions clinical care. The
scale Mosaic has a very good performance for the sensitivity but not the
specificity. The indicators in the studies are very different. This poses a
reflection: what is the sense of the indicators when the rated instrument is part
of a multifactorial prevention project whose implementation, usually, improves
the level of security by preventing the occurrence of the event? Analysis of the
tool can not be based only on numerical data. The true value of each scale is the
level of attention that triggers in Health Care Workers, which activate
preventive measures that allow an efficient management of risk. CONCLUSION: the
card Mosaic has been adopted in Ausl because it improved the level of security of
patients with risk of fall.
PMID- 25134508
TI - [E-learning and university nursing education: an overview of reviews].
AB - INTRODUCTION: The increasing use of digital technologies and e-learning in
nursing education and the health professions was also reflected in the time to
many studies and reviews. The aim of this overview was to analyze education
through e-learning technologies for nursing and health professional students.
METHOD: A comprehensive search of literature was conducted using database
PubMed/MEDLINE, Ebsco/CINAHL, 2003-2013. RESULT: The search strategy resulted in
the inclusion, in first instance, of 9732 items. After the reduction of
duplicates, applying limits and other parameters of inclusion/exclusion and, at
the end, evaluation of quality through AMSTARD check list, we included in this
overview, 22 reviews. The analized reviews were allowed to spread in different
topic areas: study population (students and faculty), e-learning methods (blended
learning Game/3D/situated learning) and evaluation (information technology,
learning satisfaction comparison of e-learning with the traditional teaching
methods) CONCLUSION: This overview demonstrates that e-learning in nursing
academic education is a valid alternative to traditional learning. If e-learning
activities are well structured and modulated, some advantages and economies are
clear possible. Regard effects of e-learning on the improvement of ability, data
are at the momenti limited when compared to traditional learning. Often e
learning appear as an adjunct respect traditional learning, but is necessary
consider e-learning and digital tecnology as priority for the future of education
of nursing students.
PMID- 25134509
TI - Clinical teaching models for nursing practice: a review of literature.
AB - INTRODUCTION: Clinical placements provide opportunities for student nurses to
learn experientially, thanks to clinical - practical teaching models. For this
purpose this review wanted to better investigate the latest methods developed in
nursing education to ameliorate the theory practice model in nursing education
teaching model. METHODS: The review of the literature was performed through a
search of nursing specific data bases, including Cinahl, Capsur, Ovid, Cockrane
Library, PubMed from January 2010 to September 2012. It included key words, such
as: Clinical Model; Nursing Education Model; Nursing Practical Teaching Model;
Theory-Practice Model. RESULTS: A total of 8 articles were found. Of these, only
4 articles were considered for this review because they better analyzed one
clinical teaching model in nursing practice. Each article was structured
analyzed, by considering the "PICOS" method, with reference to participants,
interventions, comparisons, outcomes, and study design. DISCUSSION: Four
innovative clinical teaching models for nursing practice were considered: the
first one was the Problem-Based Leaning method in nursing education; the second
one was the Self-Regulated Learning strategy; the third one was the developing
nursing students' reflective skills associated as a key component in the
perceived coherence between theory and practice; the fourth one was the computer
based clinical simulation. CONCLUSION: Each work performed an innovative clinical
teaching model for nursing student. Some limitations were highlight, but all the
literature revised emphasized the evaluation and feedback from students and the
perceptions of their clinical activities is essential.
PMID- 25134510
TI - Liver: a variant of FGF19 protects the liver from cholestatic injury without
inducing cancer.
PMID- 25134511
TI - Genetics of gastric cancer.
AB - Gastric cancer remains highly prevalent and accounts for a notable proportion of
global cancer mortality. This cancer is also associated with poor survival rates.
Understanding the genetic basis of gastric cancer will offer insights into its
pathogenesis, help identify new biomarkers and novel treatment targets, aid
prognostication and could be central to developing individualized treatment
strategies in the future. An inherited component contributes to <3% of gastric
cancers; the majority of genetic changes associated with gastric cancer are
acquired. Over the past few decades, advances in technology and high-throughput
analysis have improved understanding of the molecular aspects of the pathogenesis
of gastric cancer. These aspects are multifaceted and heterogeneous and represent
a wide spectrum of several key genetic influences, such as chromosomal
instability, microsatellite instability, changes in microRNA profile, somatic
gene mutations or functional single nucleotide polymorphisms. These genetic
aspects of the pathogenesis of gastric cancer will be addressed in this Review.
PMID- 25134512
TI - Endoscopy: a window into the gut--real-time visualization of the effects of food
intolerance using confocal laser endomicroscopy.
PMID- 25134513
TI - Learning Style Scales: a valid and reliable questionnaire.
AB - PURPOSE: Learning-style instruments assist students in developing their own
learning strategies and outcomes, in eliminating learning barriers, and in
acknowledging peer diversity. Only a few psychometrically validated learning
style instruments are available. This study aimed to develop a valid and reliable
learning-style instrument for nursing students. METHODS: A cross-sectional survey
study was conducted in two nursing schools in two countries. A purposive sample
of 156 undergraduate nursing students participated in the study. Face and content
validity was obtained from an expert panel. The LSS construct was established
using principal axis factoring (PAF) with oblimin rotation, a scree plot test,
and parallel analysis (PA). The reliability of LSS was tested using Cronbach's
alpha, corrected item-total correlation, and test-retest. RESULTS: Factor
analysis revealed five components, confirmed by PA and a relatively clear curve
on the scree plot. Component strength and interpretability were also confirmed.
The factors were labeled as perceptive, solitary, analytic, competitive, and
imaginative learning styles. Cronbach's alpha was >0.70 for all subscales in both
study populations. The corrected item-total correlations were >0.30 for the items
in each component. CONCLUSION: The LSS is a valid and reliable inventory for
evaluating learning style preferences in nursing students in various
multicultural environments.
PMID- 25134514
TI - Cross-national validation of prognostic models predicting sickness absence and
the added value of work environment variables.
AB - PURPOSE: To validate Dutch prognostic models including age, self-rated health and
prior sickness absence (SA) for ability to predict high SA in Danish eldercare.
The added value of work environment variables to the models' risk discrimination
was also investigated. METHODS: 2,562 municipal eldercare workers (95% women)
participated in the Working in Eldercare Survey. Predictor variables were
measured by questionnaire at baseline in 2005. Prognostic models were validated
for predictions of high (>=30) SA days and high (>=3) SA episodes retrieved from
employer records during 1-year follow-up. The accuracy of predictions was
assessed by calibration graphs and the ability of the models to discriminate
between high- and low-risk workers was investigated by ROC-analysis. The added
value of work environment variables was measured with Integrated Discrimination
Improvement (IDI). RESULTS: 1,930 workers had complete data for analysis. The
models underestimated the risk of high SA in eldercare workers and the SA
episodes model had to be re-calibrated to the Danish data. Discrimination was
practically useful for the re-calibrated SA episodes model, but not the SA days
model. Physical workload improved the SA days model (IDI = 0.40; 95% CI 0.19
0.60) and psychosocial work factors, particularly the quality of leadership (IDI
= 0.70; 95% CI 053-0.86) improved the SA episodes model. CONCLUSIONS: The
prognostic model predicting high SA days showed poor performance even after
physical workload was added. The prognostic model predicting high SA episodes
could be used to identify high-risk workers, especially when psychosocial work
factors are added as predictor variables.
PMID- 25134516
TI - Utilization of deletion bins to anchor and order sequences along the wheat 7B
chromosome.
AB - KEY MESSAGE: A total of 3,671 sequence contigs and scaffolds were mapped to
deletion bins on wheat chromosome 7B providing a foundation for developing high
resolution integrated physical map for this chromosome. Bread wheat (Triticum
aestivum L.) has a large, complex and highly repetitive genome which is
challenging to assemble into high quality pseudo-chromosomes. As part of the
international effort to sequence the hexaploid bread wheat genome by the
international wheat genome sequencing consortium (IWGSC) we are focused on
assembling a reference sequence for chromosome 7B. The successful completion of
the reference chromosome sequence is highly dependent on the integration of
genetic and physical maps. To aid the integration of these two types of maps, we
have constructed a high-density deletion bin map of chromosome 7B. Using the 270
K Nimblegen comparative genomic hybridization (CGH) array on a set of cv. Chinese
spring deletion lines, a total of 3,671 sequence contigs and scaffolds (~7.8 % of
chromosome 7B physical length) were mapped into nine deletion bins. Our method of
genotyping deletions on chromosome 7B relied on a model-based clustering
algorithm (Mclust) to accurately predict the presence or absence of a given
genomic sequence in a deletion line. The bin mapping results were validated using
three different approaches, viz. (a) PCR-based amplification of randomly selected
bin mapped sequences (b) comparison with previously mapped ESTs and (c)
comparison with a 7B genetic map developed in the present study. Validation of
the bin mapping results suggested a high accuracy of the assignment of 7B
sequence contigs and scaffolds to the 7B deletion bins.
PMID- 25134517
TI - Spine-like nanostructured carbon interconnected by graphene for high-performance
supercapacitors.
AB - Recent studies on supercapacitors have focused on the development of hierarchical
nanostructured carbons by combining two-dimensional graphene and other conductive
sp(2) carbons, which differ in dimensionality, to improve their electrochemical
performance. Herein, we report a strategy for synthesizing a hierarchical
graphene-based carbon material, which we shall refer to as spine-like
nanostructured carbon, from a one-dimensional graphitic carbon nanofiber by
controlling the local graphene/graphitic structure via an expanding process and a
co-solvent exfoliation method. Spine-like nanostructured carbon has a unique
hierarchical structure of partially exfoliated graphitic blocks interconnected by
thin graphene sheets in the same manner as in the case of ligaments. Owing to the
exposed graphene layers and interconnected sp(2) carbon structure, this
hierarchical nanostructured carbon possesses a large, electrochemically
accessible surface area with high electrical conductivity and exhibits high
electrochemical performance.
PMID- 25134518
TI - Primary pulmonary myxoid sarcomas with EWSR1-CREB1 translocation might originate
from primitive peribronchial mesenchymal cells undergoing (myo)fibroblastic
differentiation.
AB - Primary pulmonary myxoid sarcoma (PPMS) is a very rare lung tumor that has
recently been shown to harbor an EWSR1-CREB1 translocation. However, the
histogenesis and biological behavior of PPMS remains unclear. To provide insight
into the histogenesis of PPMS, we studied surgical resection specimens of four
patients, two females and two males with an age range of 26 to 65 years, all non
smokers with mild anemia. The tumors, three of which are endobronchial, measured
between 4 and 13 cm. One patient developed metastasis to the contra-lateral lung
7 months after resection. Other patients remained alive without tumor for 1.5,
10, and 13 years. Fluorescence in situ hybridization (FISH) analysis with a gene
break apart probe showed an EWSR1 translocation in all cases. The EWSR1-CREB1
fusion transcript was detected in all cases by reverse-transcription PCR.
Immunohistochemical staining showed diffuse positive staining of the tumor cells
only for vimentin. Tumor cells expressed no other myoid, epithelial, endothelial,
melanocytic, myoepithelial, or neuroendocrine markers, except for smooth muscle
actin and epithelial membrane antigen, which were only focally positive in
individual cases. Ultrastructural analyses revealed the presence in the tumor
cells of intermediate filaments with focal densities along the sub-cytoplasmic
membrane as well as dense plaques. These results suggest that PPMS exhibits
myofibroblastic differentiation. We conclude that PPMS is an intermediate grade
malignant lung tumor harboring EWSR1 translocations, which may originate from
mesenchymal cells that undergo fibroblastic or myofibroblastic differentiation.
PMID- 25134519
TI - Theoretical and experimental search for ZnSb-based thermoelectric materials.
AB - We report a combined theoretical and experimental search for thermoelectric
materials based on semiconducting zinc antimony. Influence of three new doping
elements (sodium, potassium and boron) on the electronic properties was
investigated as well as the carrier concentration and temperature dependence of
the thermoelectric coefficients obtained through density-functional calculations
and Boltzmann transport theory. Distortion of the electron arrangement caused by
the doping elements is displayed as a deformation charge density around the
atoms. Based on the band structures, the density of states, and the transport
properties, we found that the presence of Na and K in the ZnSb matrix leads to a
slightly improved p-type conductivity, whereas the B substitution leads to a n
type doping. Because of the stronger need for obtaining n-type ZnSb-based
material, the B(0.01)Zn(0.99)Sb structure has been transferred to the laboratory
to be synthesized by direct melting. The sample was investigated using x-ray
diffraction and scanning electron microscopy.
PMID- 25134520
TI - Location-specific expression of chemokines, TNF-alpha and S100 proteins in a teat
explant model.
AB - The distal compartments of the udder are the first to interact with invading
pathogens. The regulatory and effector functions of two major teat regions
[Furstenberg's rosette (FR); teat cistern (TC)] are largely unknown. The
objective of this study was to establish an in vitro model with explants of the
FR and the TC to analyse their response towards Escherichia coli LPS and
Staphylococcus aureus lipoteichoic acid (LTA). Quantitative stereological
analysis confirmed differences in the cellular composition of FR and TC explants.
Chemokine (CXCL8, CCL5, CCL20) and TNF-alpha mRNA were expressed at low levels in
both locations. Explant stimulation with LPS increased the mRNA abundance of all
tested chemokines and TNF-alpha. Stimulation with LTA only induced CCL20 and
CXCL8. LPS- and LTA-stimulated explant supernatants contained CXCL8 and CXCL3.
Supernatants significantly attracted neutrophils in vitro. Compared with TC, the
FR showed high constitutive mRNA expression of S100 proteins (A8, A9, A12). In
the TC, both LPS and LTA significantly induced S100A8, whereas S100A9 and S100A12
expression was only induced by LPS. The novel model system underpins the role of
the teat for recognising pathogens and shaping a pathogen- and location-specific
immune response.
PMID- 25134515
TI - Specificity, propagation, and memory of pericentric heterochromatin.
AB - The cell establishes heritable patterns of active and silenced chromatin via
interacting factors that set, remove, and read epigenetic marks. To understand
how the underlying networks operate, we have dissected transcriptional silencing
in pericentric heterochromatin (PCH) of mouse fibroblasts. We assembled a
quantitative map for the abundance and interactions of 16 factors related to PCH
in living cells and found that stably bound complexes of the histone
methyltransferase SUV39H1/2 demarcate the PCH state. From the experimental data,
we developed a predictive mathematical model that explains how chromatin-bound
SUV39H1/2 complexes act as nucleation sites and propagate a spatially confined
PCH domain with elevated histone H3 lysine 9 trimethylation levels via chromatin
dynamics. This "nucleation and looping" mechanism is particularly robust toward
transient perturbations and stably maintains the PCH state. These features make
it an attractive model for establishing functional epigenetic domains throughout
the genome based on the localized immobilization of chromatin-modifying enzymes.
PMID- 25134521
TI - Immunization with malondialdehyde-modified low-density lipoprotein (LDL) reduces
atherosclerosis in LDL receptor-deficient mice challenged with Porphyromonas
gingivalis.
AB - Periodontal infections increase the risk of atherosclerotic vascular disease via
partly unresolved mechanisms. Of the natural IgM Abs that recognize molecular
mimicry on bacterial epitopes and modified lipid and protein structures, IgM
directed against oxidized low-density lipoprotein (LDL) is associated with
atheroprotective properties. Here, the effect of natural immune responses to
malondialdehyde-modified LDL (MDA-LDL) in conferring protection against
atherosclerosis, which was accelerated by the major periodontopathogen
Porphyromonas gingivalis, was investigated. LDL receptor-deficient (LDLR(-/-))
mice were immunized with mouse MDA-LDL without adjuvant before topical
application challenge with live P. gingivalis. Atherosclerosis was analyzed after
a high-fat diet, and plasma IgG and IgM Ab levels were measured throughout the
study, and the secretion of IL-5, IL-10 and IFN-gamma in splenocytes stimulated
with MDA-LDL was determined. LDLR(-/-) mice immunized with MDA-LDL had elevated
IgM and IgG levels to MDA-LDL compared with saline-treated controls. MDA-LDL
immunization diminished aortic lipid depositions after challenge with P.
gingivalis compared with mice receiving only P. gingivalis challenge.
Immunization of LDLR(-/-) mice with homologous MDA-LDL stimulated the production
of IL-5, implicating general activation of B-1 cells. Immune responses to MDA-LDL
protected from the P. gingivalis-accelerated atherosclerosis. Thus, the linkage
between bacterial infectious burden and atherogenesis is suggested to be
modulated via natural IgM directed against cross-reactive epitopes on bacteria
and modified LDL.
PMID- 25134522
TI - Advancing the application of systems thinking in health: exploring dual practice
and its management in Kampala, Uganda.
AB - BACKGROUND: Many full-time Ugandan government health providers take on additional
jobs - a phenomenon called dual practice. We describe the complex patterns that
characterize the evolution of dual practice in Uganda, and the local management
practices that emerged in response, in five government facilities. An in-depth
understanding of dual practice can contribute to policy discussions on improving
public sector performance. METHODS: A multiple case study design with embedded
units of analysis was supplemented by interviews with policy stakeholders and a
review of historical and policy documents. Five facility case studies captured
the perspective of doctors, nurses, and health managers through semi-structured
in-depth interviews. A causal loop diagram illustrated interactions and feedback
between old and new actors, as well as emerging roles and relationships. RESULTS:
The causal loop diagram illustrated how feedback related to dual practice policy
developed in Uganda. As opportunities for dual practice grew and the public
health system declined over time, government providers increasingly coped through
dual practice. Over time, government restrictions to dual practice triggered
policy resistance and protest from government providers. Resulting feedback
contributed to compromising the supply of government providers and, potentially,
of service delivery outcomes. Informal government policies and restrictions
replaced the formal restrictions identified in the early phases. In some
instances, government health managers, particularly those in hospitals, developed
their own practices to cope with dual practice and to maintain public sector
performance. Management practices varied according to the health manager's
attitude towards dual practice and personal experience with dual practice. These
practices were distinct in hospitals. Hospitals faced challenges managing
internal dual practice opportunities, such as those created by externally-funded
research projects based within the hospital. Private wings' inefficiencies and
strict fee schedule made them undesirable work locations for providers.
CONCLUSIONS: Dual practice prevails because public and private sector incentives,
non-financial and financial, are complementary. Local management practices for
dual practice have not been previously documented and provide learning
opportunities to inform policy discussions. Understanding how dual practice
evolves and how it is managed locally is essential for health workforce policy,
planning, and performance discussions in Uganda and similar settings.
PMID- 25134524
TI - Steps per Day, Daily Peak Stepping Cadence, and Walking Performance in Older
Adults.
AB - We tested the hypothesis that the intensity of daily ambulation would relate with
functional walking capacity in older adults. Forty-three women (n = 25) and men
(n = 18) between the ages of 60-78 years wore an accelerometer for measurement of
average daily steps and 30-min peak stepping cadence. A 400-m walk test was used
to measure walking speed. No sex difference was found for average daily steps (p
= .76), average peak cadence (p = .96), or walking speed (p = .89). Daily steps
(women: r = .68, p < .01; men: r = .04) and peak cadence (women: r = .81, p <
.01; men: r = -.16) were positively correlated with walking speed in women but
not in men. After controlling for daily steps, peak cadence remained
significantly associated with walking speed in women (partial r = .61, p < .01).
Walking intensity during daily ambulation is independently related to functional
walking capacity in older adults, albeit this relation may be more significant
for women than men.
PMID- 25134525
TI - Skeletal muscle work efficiency with age: the role of non-contractile processes.
AB - Although skeletal muscle work efficiency probably plays a key role in limiting
mobility of the elderly, the physiological mechanisms responsible for this
diminished function remain incompletely understood. Thus, in the quadriceps of
young (n=9) and old (n=10) subjects, we measured the cost of muscle contraction
(ATP cost) with 31P-magnetic resonance spectroscopy (31P-MRS) during (i) maximal
intermittent contractions to elicit a metabolic demand from both cross-bridge
cycling and ion pumping and (ii) a continuous maximal contraction to
predominantly tax cross-bridge cycling. The ATP cost of the intermittent
contractions was significantly greater in the old (0.30+/-0.22 mM.min-1.N.m-1)
compared with the young (0.13+/-0.03 mM.min-1.N.m-1, P<0.05). In contrast, at the
end of the continuous contraction protocol, the ATP cost in the old (0.10+/-0.07
mM.min-1.N.m-1) was not different from the young (0.06+/-0.02 mM.min-1.N.m-1,
P=0.2). In addition, the ATP cost of the intermittent contractions correlated
significantly with the single leg peak power of the knee-extensors assessed
during incremental dynamic exercise (r=-0.55; P<0.05). Overall, this study
reveals an age-related increase in the ATP cost of contraction, probably mediated
by an excessive energy demand from ion pumping, which probably contributes to
both the decline in muscle efficiency and functional capacity associated with
aging.
PMID- 25134523
TI - Transcriptome sequencing of a chimaera reveals coordinated expression of
anthocyanin biosynthetic genes mediating yellow formation in herbaceous peony
(Paeonia lactiflora Pall.).
AB - BACKGROUND: Herbaceous peony (Paeonia lactiflora Pall.) is a traditional flower
in China and a wedding attractive flower in worldwide. In its flower colour,
yellow is the rarest which is ten times the price of the other colours. However,
the breeding of new yellow P. lactiflora varieties using genetic engineering is
severely limited due to the little-known biochemical and molecular mechanisms
underlying its characteristic formation. RESULTS: In this study, two cDNA
libraries generated from P. lactiflora chimaera with red outer-petal and yellow
inner-petal were sequenced using an Illumina HiSeqTM 2000 platform. 66,179,398
and 65,481,444 total raw reads from red outer-petal and yellow inner-petal cDNA
libraries were generated, which were assembled into 61,431 and 70,359 Unigenes
with an average length of 628 and 617 nt, respectively. Moreover, 61,408 non
redundant All-unigenes were obtained, with 37,511 All-unigenes (61.08%) annotated
in public databases. In addition, 6,345 All-unigenes were differentially
expressed between the red outer-petal and yellow inner-petal, with 3,899 up
regulated and 2,446 down-regulated All-unigenes, and the flavonoid metabolic
pathway related to colour development was identified using the Kyoto encyclopedia
of genes and genomes database (KEGG). Subsequently, the expression patterns of 10
candidate differentially expressed genes (DEGs) involved in the flavonoid
metabolic pathway were examined, and flavonoids were qualitatively and
quantitatively analysed. Numerous anthoxanthins (flavone and flavonol) and a few
anthocyanins were detected in the yellow inner-petal, which were all lower than
those in the red outer-petal due to the low expression levels of the
phenylalanine ammonialyase gene (PlPAL), flavonol synthase gene (PlFLS),
dihydroflavonol 4-reductase gene (PlDFR), anthocyanidin synthase gene (PlANS),
anthocyanidin 3-O-glucosyltransferase gene (Pl3GT) and anthocyanidin 5-O
glucosyltransferase gene (Pl5GT). CONCLUSION: Transcriptome sequencing (RNA-Seq)
analysis based on the high throughput sequencing technology was an efficient
approach to identify critical genes in P. lactiflora and other non-model plants.
The flavonoid metabolic pathway and glucide metabolic pathway were identified as
relatived yellow formation in P. lactiflora, PlPAL, PlFLS, PlDFR, PlANS, Pl3GT
and Pl5GT were selected as potential candidates involved in flavonoid metabolic
pathway, which inducing inhibition of anthocyanin biosynthesis mediated yellow
formation in P. lactiflora. This study could lay a theoretical foundation for
breeding new yellow P. lactiflora varieties.
PMID- 25134526
TI - SCM-198 inhibits microglial overactivation and attenuates Abeta(1-40)-induced
cognitive impairments in rats via JNK and NF-kB pathways.
AB - BACKGROUND: Neuroinflammation mediated by overactivated microglia plays a key
role in many neurodegenerative diseases, including Alzheimer's disease (AD). In
this study, we investigated for the first time the anti-neuroinflammatory effects
and possible mechanisms of SCM-198 (an alkaloid extracted from Herbaleonuri),
which was previously found highly cardioprotective, both in vitro and in vivo.
METHODS: For in vitro experiments, lipopolysaccharide (LPS) or beta-amyloid(1-40)
(Abeta(1-40)) was applied to induce microglial overactivation. Proinflammatory
mediators were measured and activations of NF-kappaB and mitogen-activated
protein kinases' (MAPKs) pathways were investigated. Further protective effect of
SCM-198 was evaluated in microglia-neuron co-culture assay and Sprague-Dawley
(SD) rats intrahippocampally-injected with Abeta(1-40). RESULTS: SCM-198 reduced
expressions of nitric oxide (NO), TNF-alpha, IL-1beta and IL-6 possibly via, at
least partially, inhibiting c-Jun N-terminal kinase (JNK) and NF-kappaB signaling
pathways in microglia. Co-culture assay showed that activated microglia
pretreated with SCM-198 led to less neuron loss and decreased phosphorylation of
tau and extracellular signal-regulated kinase (ERK) in neurons. Besides, SCM-198
also directly protected against Abeta(1-40)-induced neuronal death and lactate
dehydrogenase (LDH) release in primary cortical neurons. For in vivo studies, SCM
198 significantly enhanced cognitive performances of rats 12 days after
intrahippocampal injections of aged Abeta(1-40) peptides in the Morris water maze
(MWM), accompanied by less hippocampal microglial activation, decreased
synaptophysin loss and phosphorylation of ERK and tau. Co-administration of
donepezil and SCM-198 resulted in a slight cognitive improvement in SD rats 50
days after intrahippocampal injections of aged Abeta(1-40) peptides as compared
to only donepezil or SCM-198 treated group. CONCLUSIONS: Our findings are the
first to report that SCM-198 has considerable anti-neuroinflammatory effects on
inhibiting microglial overactivation and might become a new potential drug
candidate for AD therapy in the future.
PMID- 25134528
TI - Radioiodine therapy for thyroid cancer in the era of risk stratification and
alternative targeted therapies.
AB - Differentiated thyroid cancers are typically iodine-avid and can be effectively
treated with radioiodine. In most patients, radioiodine treatment is done for
ablation of residual tissue, and in these cases the focus should be on using the
minimum effective dose. Adjuvant therapy can be done to reduce the risk of
recurrence, but optimal patient selection and dose are unclear. Patients with
advanced disease benefit most from treatment with the maximum-tolerated dose.
Recent research has focused on better patient selection and reduced radioiodine
doses for remnant ablation. There are emerging targeted therapeutic approaches in
patients who are appropriately shown to have iodine-refractory disease, with 1
drug approved by the Food and Drug Administration. Numerous trials are ongoing to
assess targeted therapeutics alone or in combination with radioiodine.
PMID- 25134529
TI - Segmentation-based MR attenuation correction including bones also affects
quantitation in brain studies: an initial result of 18F-FP-CIT PET/MR for
patients with parkinsonism.
AB - Attenuation correction (AC) with an ultrashort echo time (UTE) sequence has
recently been used in combination with segmentation for cortical bone
identification for brain PET/MR studies. The purpose of this study was to
evaluate the quantification of (18)F-fluoropropyl
carbomethoxyiodophenylnortropane ((18)F-FP-CIT) binding in brain PET/MR,
particularly focusing on effects of UTE-based AC including bone segmentation.
METHODS: Sixteen patients with initially suspected parkinsonism were
prospectively enrolled. An emission scan was acquired 110 min after (18)F-FP-CIT
injection on a dedicated PET/MR scanner, immediately followed by another emission
scan using a PET/CT scanner 120 min after the injection. A UTE-based attenuation
map was used to classify the voxels into 3 tissues: bone, soft tissue, and air.
All PET images were spatially normalized, and a specific-to-nonspecific dopamine
transporter (DAT) binding ratio (BR) was calculated using statistical
probabilistic anatomic mapping. The level of agreement was assessed with
intraclass correlation coefficients (ICCs). Voxelwise comparison between PET
images acquired from PET/MR and PET/CT was performed. We compared non-attenuation
corrected images to analyze UTE-based AC effects on DAT quantification. RESULTS:
BR in the putamen obtained from PET/MR and PET/CT showed low interequipment
variability, whereas BR in the caudate nucleus showed significant variability
(ICC = 0.967 and 0.682 for putamen and caudate nucleus, respectively). BR in the
caudate nucleus was significantly underestimated by PET/MR, compared with PET/CT
(mean difference of BR = 0.66, P < 0.0001). Voxelwise analysis revealed that
PET/MR showed significantly low BR in the periventricular regions, which was
caused by a misclassification of the ventricle as air on the attenuation map. We
also compared non-AC images, revealing low interequipment variability even in the
caudate nucleus (ICC = 0.937 and 0.832 for putamen and caudate nucleus,
respectively). CONCLUSION: Our data demonstrate spatial bias of the DAT BR on
(18)F-FP-CIT PET/MR. Voxelwise analysis and comparison to non-AC images
identified the misclassification of ventricle as air to be the cause of bias. To
obtain reliable quantification for brain PET/MR studies including (18)F-FP-CIT
PET, alternative and more reliable segmentation strategies are required.
PMID- 25134527
TI - The impact of S6K1 kinase on neuroblastoma cell proliferation is independent of
GLI1 signaling.
AB - BACKGROUND: The crosstalk between Hedgehog (HH) signaling and other signal
transduction cascades has been extensively studied in different cancers. In
neuroblastoma, mTOR/S6K1 signaling is known to have a role in the development of
this disease and recent evidence also implicates the HH pathway. Moreover, S6K1
kinase has been shown to phosphorylate GLI1, the effector of HH signaling,
promoting GLI1 transcriptional activity and oncogenic function in esophageal
adenocarcinoma. In this study, we examined the possible interplay of S6K1 and
GLI1 signaling in neuroblastoma. METHODS: siRNA knockdowns were used to suppress
S6K1 and GLI1 expression, and the siRNA effects were validated by real-time PCR
and Western blotting. Cell proliferation analysis was performed with the EdU
incorporation assay. Cytotoxic analysis with increasing concentrations of
PI3K/mTOR and GLI inhibitors, individually and in combination, was used to
determine drug response. RESULTS: Although knockdown of either S6K1 or GLI1
reduces the cellular proliferation of neuroblastoma cells, there is little effect
of S6K1 on the expression of GLI1 mRNA and protein and on the capacity of GLI1 to
activate target genes. No detectable phosphorylation of GLI1 is observed prior or
following S6K1 knockdown. GLI1 overexpression can not rescue the reduced
proliferation elicited by S6K1 knockdown. Moreover, inhibitors of PI3K/mTOR and
GLI signaling reduced neuroblastoma cell growth, but no additional growth
inhibitory effects were detected when the two classes of drugs were combined.
CONCLUSION: Our results demonstrate that the impact of S6K1 kinase on
neuroblastoma cells is not mediated through modulation of GLI1
expression/activity.
PMID- 25134530
TI - Socioeconomic factors and effect of evidence-based patient information about
primary prevention of type 2 diabetes mellitus--are there interactions?
AB - BACKGROUND: Having shown in a recent randomized controlled trial that evidence
based patient information (EBPI) significantly increased knowledge on primary
prevention of diabetes compared to standard patient information, we now
investigated interaction between socioeconomic status (SES) and the effect of an
EBPI. FINDINGS: 1,120 visitors (aged 40-70 years, without known diabetes) to the
"Techniker Krankenkasse" and the "German Diabetes Center" websites were
randomized. The intervention group received a newly developed on-line EBPI, the
control group standard on-line information. The primary outcome measure was
knowledge, classified as "good/average/poor". We analyzed associations of
knowledge with socioeconomic variables (education, vocational training,
employment, subjective social status) combined with intervention effect including
interactions, adjusted for possible confounding by knowledge before intervention,
self-reported blood glucose measurements, blood pressure, blood lipid levels, age
and gender. Logistic regression models were fitted to the subpopulation (n = 647)
with complete values in these variables.Education (high vs. low) was
significantly associated with knowledge (good vs. average/poor); however, there
was no significant interaction between education and intervention. After
adjustment, the other socioeconomic variables were not significantly associated
with knowledge. CONCLUSIONS: Socioeconomic variables did not significantly change
the effect of the intervention. There was a tendency towards a lower effect where
lower educated individuals were concerned. Possibly the power was too low to
detect interaction effects. Larger studies using SES-specific designs are needed
to clarify the effect of SES. We suggest considering the socioeconomic status
when evaluating a decision aid, e.g. an EBPI, to ensure its effectiveness not
only in higher socioeconomic groups. TRIAL REGISTRATION: Current Controlled
Trials ISRCTN22060616 (Date assigned: 12 September 2008).
PMID- 25134531
TI - The use of an adjustable electrode housing unit to compare electrode alignment
and contact variation with myoelectric prosthesis functionality: A pilot study.
AB - BACKGROUND: Usable myoelectric control relies on secure and intimate contact at
all times between the electrode, the socket and the residual limb. At present,
there is little post-fitting socket adjustment available to prosthetists with
respect to electrode contact security or alignment. Failure to provide secure
electrode contact could result in the development of motion artefacts, poor
prehensor response and subsequent prosthesis non-usage. OBJECTIVES: To establish
the effect of alteration to electrode contract security and alignment on
prosthesis functionality using a bespoke electrode housing unit. STUDY DESIGN:
This study investigated the effect of electrode contact security and alignment on
upper limb myoelectric prosthesis functionality. METHODS: Four different
electrode housing arrangements were assessed within prosthetic sockets fitted to
six transradial prosthesis subjects using the Southampton Hand Assessment
Procedure, which is a reliable and validated prosthesis functionality assessment
tool. RESULTS: Significantly higher functionality scores were achieved with the
bespoke housing unit compared to when using conventional electrode housings.
CONCLUSION: Myoelectric prosthesis functionality is closely linked to electrode
contact security and to electrode alignment with respect to the residual limb.
Both of these factors can be improved locally using an adjustable electrode
housing unit. CLINICAL RELEVANCE: Provision of an electrode housing system that
enables adjustments to be made to electrode orientation can improve prosthesis
functionality, particularly in cases where tight-fitting sockets are not
possible, and/or where the prosthetist may be inexperienced with regard to
myoelectric prosthesis fitting.
PMID- 25134532
TI - Efficacy of a newly designed trunk orthosis with joints providing resistive force
in adults with post-stroke hemiparesis.
AB - BACKGROUND: Few studies have examined the efficacy of trunk orthoses that support
the upper trunk and a paretic limb in stroke patients. To improve stability and
alignment of the trunk and pelvis in hemiparetic patients, we developed a newly
designed trunk orthosis that provides resistive force through spring joints.
OBJECTIVES: This study aimed to determine the newly designed trunk orthosis's
biomechanical effects during level walking. STUDY DESIGN: Before-after trials
must be better. METHODS: Measurements were taken for nine chronic-phase (>2 years
post-onset) stroke patients using a three-dimensional motion capture system and
force plates under three experimental conditions: self-selected gait speed
without the newly designed trunk orthosis, with the newly designed trunk
orthosis, and after newly designed trunk orthosis removal. We analyzed and
compared spatiotemporal and kinetic parameters of the paretic and non-paretic
limbs and kinematic parameters of the trunk and bilateral limbs. RESULTS: Several
pre-swing gait parameters (e.g. hip joint flexion moment and ankle joint plantar
flexion angle) after newly designed trunk orthosis removal were significantly
increased compared to those without newly designed trunk orthosis. Step length of
the paretic limb tended to increase after newly designed trunk orthosis removal.
CONCLUSION: The newly designed trunk orthosis effectively modified trunk
alignment, but larger improvements in kinetic and kinematic parameters were
observed in the bilateral limbs after newly designed trunk orthosis removal than
with the newly designed trunk orthosis. CLINICAL RELEVANCE: Stroke patients
improved only trunk malalignment while wearing the newly designed trunk orthosis.
Gait after newly designed trunk orthosis removal was better than with the newly
designed trunk orthosis. Positive changes after removal were mostly observed in
pre-swing of the hemiparetic limb. The newly designed trunk orthosis might be
effective for gait training in stroke patients.
PMID- 25134533
TI - Minimal clinically important difference of the L Test for individuals with lower
limb amputation: A pilot study.
AB - BACKGROUND: The L Test is a reliable/valid clinical evaluation of mobility that
measures walking speed in seconds. It can be used with individuals with lower
limb amputation. Responsiveness of the L Test is not yet determined. OBJECTIVES:
The purpose of this pilot study was to determine how well the L Test identified
individuals with a lower limb amputation who have/have not undergone a minimal
clinically important difference. STUDY DESIGN: Prospective follow-up study.
METHODS: In total, 33 individuals with lower limb amputation, deemed to require a
major intervention, were recruited consecutively from a follow-up clinic.
Participants completed the L Test at baseline and follow-up. A Global Rating
Change scale was also completed at follow-up. RESULTS: The participants had a
mean age +/- standard deviation of 60 +/- 13.0 years, and 81.8% had a transtibial
amputation. The mean +/- standard deviation for the L Test change scores was 6.0
+/- 13.9. The area under the curve was 0.67, and the minimal clinically important
difference was 4.5 s. CONCLUSIONS: The L Test identified individuals as having an
important clinical change. Results must be interpreted with caution, as the
accuracy, based on the Global Rating Change scale, is low. Further inquiry into
the L Test is encouraged. CLINICAL RELEVANCE: The L Test can guide the clinical
management of individuals with lower limb amputation. Results from this pilot
study indicate that individuals with a lower limb amputation who improve by at
least 4.5 s on the L Test after an intervention have likely undergone an
important change. This result must be interpreted with caution given that the
ability of the L Test to correctly identify individuals, who have and have not
undergone an important change, using the Global Rating Change scale as the gold
standard, is limited because this is a pilot study. It is plausible that the
precision of the cut-point threshold could increase or decrease given a larger
sample or when using a different method of identifying important clinical change.
PMID- 25134534
TI - Genome-wide association study identifies new susceptibility loci for epithelial
ovarian cancer in Han Chinese women.
AB - Ovarian cancer is the leading cause of death from gynaecological malignancies
worldwide. Here we perform a three-stage genome-wide association study (GWAS) in
Han Chinese women to identify risk genetic variants for epithelial ovarian cancer
(EOC). We scan 900,015 single-nucleotide polymorphisms (SNPs) in 1,057 EOC cases
and 1,191 controls in stage I, and replicate 41 SNPs (P(meta)<10(-4)) in 960 EOC
cases and 1,799 controls (stage II), and an additional 492 EOC cases and 1,004
controls (stage III). Finally, we identify two EOC susceptibility loci at 9q22.33
(rs1413299 in COL15A1, P(meta) = 1.88 * 10(-8)) and 10p11.21 (rs1192691 near
ANKRD30A, P(meta) = 2.62 * 10(-8)), and two consistently replicated loci at
12q14.2 (rs11175194 in SRGAP1, P(meta) = 1.14 * 10(-7)) and 9q34.2 (rs633862 near
ABO and SURF6, P(meta) = 8.57 * 10(-7)) (P<0.05 in all three stages). These
results may advance our understanding of genetic susceptibility to EOC.
PMID- 25134535
TI - Atomic force microscopy of asymmetric membranes from turtle erythrocytes.
AB - The cell membrane provides critical cellular functions that rely on its elaborate
structure and organization. The structure of turtle membranes is an important
part of an ongoing study of erythrocyte membranes. Using a combination of atomic
force microscopy and single-molecule force spectroscopy, we characterized the
turtle erythrocyte membrane structure with molecular resolution in a quasi-native
state. High-resolution images both leaflets of turtle erythrocyte membranes
revealed a smooth outer membrane leaflet and a protein covered inner membrane
leaflet. This asymmetry was verified by single-molecule force spectroscopy, which
detects numerous exposed amino groups of membrane proteins in the inner membrane
leaflet but much fewer in the outer leaflet. The asymmetric membrane structure of
turtle erythrocytes is consistent with the semi-mosaic model of human, chicken
and fish erythrocyte membrane structure, making the semi-mosaic model more widely
applicable. From the perspective of biological evolution, this result may support
the universality of the semi-mosaic model.
PMID- 25134536
TI - A medium-chain fatty acid, capric acid, inhibits RANKL-induced osteoclast
differentiation via the suppression of NF-kappaB signaling and blocks
cytoskeletal organization and survival in mature osteoclasts.
AB - Fatty acids, important components of a normal diet, have been reported to play a
role in bone metabolism. Osteoclasts are bone-resorbing cells that are
responsible for many bone-destructive diseases such as osteoporosis. In this
study, we investigated the impact of a medium-chain fatty acid, capric acid, on
the osteoclast differentiation, function, and survival induced by receptor
activator of NF-kappaB ligand (RANKL) and macrophage colony-stimulating factor
(MCSF). Capric acid inhibited RANKL-mediated osteoclastogenesis in bone marrow
derived macrophages and suppressed RANKL-induced IkappaBalpha phosphorylation,
p65 nuclear translocation, and NF-kappaB transcriptional activity. Capric acid
further blocked the RANKL-stimulated activation of ERK without affecting JNK or
p38. The induction of NFATc1 in response to RANKL was also attenuated by capric
acid. In addition, capric acid abrogated M-CSF and RANKL-mediated cytoskeleton
reorganization, which is crucial for the efficient bone resorption of
osteoclasts. Capric acid also increased apoptosis in mature osteoclasts through
the induction of Bim expression and the suppression of ERK activation by M-CSF.
Together, our results reveal that capric acid has inhibitory effects on
osteoclast development. We therefore suggest that capric acid may have potential
therapeutic implications for the treatment of bone resorption-associated
disorders.
PMID- 25134540
TI - Sharp rise in CT scans prompts call for new safeguards on radiation exposure.
PMID- 25134538
TI - TAp73 and DeltaNp73 have opposing roles in 5-aza-2'-deoxycytidine-induced
apoptosis in breast cancer cells.
AB - The p73 gene contains an extrinsic P1 promoter and an intrinsic P2 promoter,
controlling the transcription of the pro-apoptotic TAp73 isoform and the anti
apoptotic DeltaNup73 isoform, respectively. The DNA methylation status of both
promoters act equally in the epigenetic transcriptional regulation of their
relevant isoforms. The aim of this study was to analyze the different effects of
these p73 isoforms in 5-aza-2'-deoxycytidine (5-aza-dC)-induced apoptosis in
breast cancer cells. We investigated the effects of the DNA demethylation agent,
5-aza-dC, on the T-47D breast cancer cell line, and evaluated the methylation
status of the p73 promoters and expression of TAp73 and DeltaNp73. Furthermore,
we assessed the expression of p53 and p73 isoforms in 5-aza-dC-treated T-47D
cells and p53 knockout cells. 5-aza-dC induced significant anti-tumor effects in
T-47D cells, including inhibition of cell viability, G1 phase arrest and
apoptosis. This was associated with p73 promoter demethylation and a concomitant
increase in TAp73 mRNA and protein expression. In contrast, the methylation
status of promoter P2 was not associated with DeltaNp73 mRNA or protein levels.
Furthermore, demethylation of P2 failed to inhibit the expression of DeltaNp73
with 5-aza-dC in the p53 knockdown cell model. Our study suggests that
demethylation of the P1 and P2 promoters has opposite effects on the expression
of p73 isoforms, namely up-regulation of TAp73 and down-regulation of DeltaNup73.
We also demonstrate that p53 likely contributes to 5-aza-dC-induced DeltaNp73
transcriptional inactivation in breast cancer cells.
PMID- 25134537
TI - Oncomodulin/truncated protamine-mediated Nogo-66 receptor small interference RNA
delivery promotes axon regeneration in retinal ganglion cells.
AB - The optic nerve often suffers regenerative failure after injury, leading to
serious visual impairment such as glaucoma. The main inhibitory factors,
including Nogo-A, oligodendrocyte myelin glycoprotein, and myelin-associated
glycoprotein, exert their inhibitory effects on axonal growth through the same
receptor, the Nogo-66 receptor (NgR). Oncomodulin (OM), a calcium-binding protein
with a molecular weight of an ~12 kDa, which is secreted from activated
macrophages, has been demonstrated to have high and specific affinity for retinal
ganglion cells (RGC) and promote greater axonal regeneration than other known
polypeptide growth factors. Protamine has been reported to effectively deliver
small interference RNA (siRNA) into cells. Accordingly, a fusion protein of OM
and truncated protamine (tp) may be used as a vehicle for the delivery of NgR
siRNA into RGC for gene therapy. To test this hypothesis, we constructed OM and
tp fusion protein (OM/tp) expression vectors. Using the indirect
immunofluorescence labeling method, OM/tp fusion proteins were found to have a
high affinity for RGC. The gel shift assay showed that the OM/tp fusion proteins
retained the capacity to bind to DNA. Using OM/tp fusion proteins as a delivery
tool, the siRNA of NgR was effectively transfected into cells and significantly
down-regulated NgR expression levels. More importantly, OM/tp-NgR siRNA
dramatically promoted axonal growth of RGC compared with the application of OM/tp
recombinant protein or NgR siRNA alone in vitro. In addition, OM/tp-NgR siRNA
highly elevated intracellular cyclic adenosine monophosphate (cAMP) levels and
inhibited activation of the Ras homolog gene family, member A (RhoA). Taken
together, our data demonstrated that the recombinant OM/tp fusion proteins
retained the functions of both OM and tp, and that OM/tp-NgR siRNA might
potentially be used for the treatment of optic nerve injury.
PMID- 25134539
TI - Indacaterol inhibits tumor cell invasiveness and MMP-9 expression by suppressing
IKK/NF-kappaB activation.
AB - The beta2 adrenergic receptor (ADRB2) is a G protein-coupled transmembrane
receptor expressed in the human respiratory tract and widely recognized as a
pharmacological target for treatments of asthma and chronic obstructive pulmonary
disorder (COPD). Although a number of ADRB2 agonists have been developed for use
in asthma therapy, indacaterol is the only ultra-long-acting inhaled beta2
agonist (LABA) approved by the FDA for relieving the symptoms in COPD patients.
The precise molecular mechanism underlying the pharmacological effect of
indacaterol, however, remains unclear. Here, we show that beta-arrestin-2
mediates the internalization of ADRB2 following indacaterol treatment. Moreover,
we demonstrate that indacaterol significantly inhibits tumor necrosis factor
alpha (TNF-alpha)-induced NF-kappaB activity by reducing levels of both
phosphorylated-IKK and -IkappaBalpha, thereby decreasing NF-kappaB nuclear
translocation and the expression of MMP-9, an NF-kappaB target gene.
Subsequently, we show that indacaterol significantly inhibits TNF-alpha/NF-kappaB
induced cell invasiveness and migration in a human cancer cell line. In
conclusion, we propose that indacaterol may inhibit NF-kappaB activity in a beta
arrestin2-dependent manner, preventing further lung damage and improving lung
function in COPD patients.
PMID- 25134541
TI - Oral susceptibility of Aedes aegypti (Diptera: Culicidae) from Senegal for dengue
serotypes 1 and 3 viruses.
AB - OBJECTIVE: To investigate the potential for domestic and wild populations of
Aedes aegypti from Dakar and Kedougou to develop a disseminated infection after
exposure to DENV-3 and DENV-1. METHODS: We have exposed sylvatic and urban
population of Ae. aegypti from Senegal to bloomeals containing dengue serotype 1
and 3. At different incubation period, individual mosquito legs/wings and bodies
were tested for virus presence using real time RT-PCR to estimate the infection
and dissemination rates. RESULTS: The data indicated low susceptibility to DENV-3
(infection: 2.4-15.2%, and dissemination rates: 0-8.3%) and higher susceptibility
to DENV-1 (infection and dissemination rates up to 50%). CONCLUSION: Aedes
aegypti from Senegal seem able to develop a disseminated infection of DENV-1 and
DENV-3. Further studies are needed to test their ability to transmit the two
serotypes.
PMID- 25134543
TI - Communication: The distinguishable cluster approximation. II. The role of orbital
relaxation.
AB - The distinguishable cluster approximation proposed in Paper I [D. Kats and F. R.
Manby, J. Chem. Phys. 139, 021102 (2013)] has shown intriguing abilities to
accurately describe potential energy surfaces in various notoriously difficult
cases. The question that still remained open is to what extend the accuracy and
the stability of the method is due to the special choice of orbital-relaxation
treatment. In this paper we introduce orbital relaxation in terms of Brueckner
orbitals, orbital optimization, and projective singles into the distinguishable
cluster approximation and investigate its importance in single- and
multireference cases. All three resulting methods are able to cope with many
multiple-bond breaking problems, but in some difficult cases where the Hartree
Fock orbitals seem to be entirely inadequate the orbital-optimized version turns
out to be superior.
PMID- 25134544
TI - Communication: Escape kinetics of self-propelled Janus particles from a cavity:
numerical simulations.
AB - We numerically investigate the escape kinetics of elliptic Janus particles from
narrow two-dimensional cavities with reflecting walls. The self-propulsion
velocity of the Janus particle is directed along either their major (prolate) or
minor (oblate) axis. We show that the mean exit time is very sensitive to the
cavity geometry, particle shape, and self-propulsion strength. The mean exit time
is found to be a minimum when the self-propulsion length is equal to the cavity
size. We also find the optimum mean escape time as a function of the self
propulsion velocity, translational diffusion, and particle shape. Thus, effective
transport control mechanisms for Janus particles in a channel can be implemented.
PMID- 25134542
TI - Cellular dosimetry calculations for Strontium-90 using Monte Carlo code PENELOPE.
AB - PURPOSE: To improve risk assessments associated with chronic exposure to
Strontium-90 (Sr-90), for both the environment and human health, it is necessary
to know the energy distribution in specific cells or tissue. Monte Carlo (MC)
simulation codes are extremely useful tools for calculating deposition energy.
The present work was focused on the validation of the MC code PENetration and
Energy LOss of Positrons and Electrons (PENELOPE) and the assessment of dose
distribution to bone marrow cells from punctual Sr-90 source localized within the
cortical bone part. MATERIALS AND METHODS: S-values (absorbed dose per unit
cumulated activity) calculations using Monte Carlo simulations were performed by
using PENELOPE and Monte Carlo N-Particle eXtended (MCNPX). Cytoplasm, nucleus,
cell surface, mouse femur bone and Sr-90 radiation source were simulated. Cells
are assumed to be spherical with the radii of the cell and cell nucleus ranging
from 2-10 MUm. The Sr-90 source is assumed to be uniformly distributed in cell
nucleus, cytoplasm and cell surface. RESULTS: The comparison of S-values
calculated with PENELOPE to MCNPX results and the Medical Internal Radiation Dose
(MIRD) values agreed very well since the relative deviations were less than 4.5%.
The dose distribution to mouse bone marrow cells showed that the cells localized
near the cortical part received the maximum dose. CONCLUSION: The MC code
PENELOPE may prove useful for cellular dosimetry involving radiation transport
through materials other than water, or for complex distributions of radionuclides
and geometries.
PMID- 25134546
TI - A renormalized potential-following propagation algorithm for solving the coupled
channels equations.
AB - We derive a general renormalized potential-following propagation method that
efficiently solves the coupled-channels equations. The step size is variable, the
method is compatible with reactive boundary conditions, and the algorithm may be
combined with other renormalized algorithms, such as renormalized Numerov. We
diagonalize the coupling matrix and consider piece-wise constant and linear
reference potentials. The constant reference potential algorithm is very simple
to implement, yet for multichannel problems almost as accurate as the linear
reference potential method. The applicability of the proposed algorithms to
realistic problems is demonstrated for cold collisions of NH radicals. The
renormalized approach has the advantage of producing wave functions in a
straightforward way, which is illustrated for a shape resonance in NH-NH
collisions. These scattering wave functions can be used to study ultracold
photoassociation and near-threshold photodissociation.
PMID- 25134545
TI - Multiple branched adaptive steered molecular dynamics.
AB - Steered molecular dynamics, SMD, [S. Park and K. Schulten, J. Chem. Phys. 120,
5946 (2004)] combined with Jarzynski's equality has been used widely in
generating free energy profiles for various biological problems, e.g., protein
folding and ligand binding. However, the calculated averages are generally
dominated by "rare events" from the ensemble of nonequilibrium trajectories. The
recently proposed adaptive steered molecular dynamics, ASMD, introduced a new
idea for selecting important events and eliminating the non-contributing
trajectories, thus decreasing the overall computation needed. ASMD was shown to
reduce the number of trajectories needed by a factor of 10 in a benchmarking
study of decaalanine stretching. Here we propose a novel, highly efficient
"multiple branching" (MB) version, MB-ASMD, which obtains a more complete
enhanced sampling of the important trajectories, while still eliminating non
contributing segments. Compared to selecting a single configuration in ASMD, MB
ASMD offers to select multiple configurations at each segment along the reaction
coordinate based on the distribution of work trajectories. We show that MB-ASMD
has all benefits of ASMD such as faster convergence of the PMF even when pulling
1000 times faster than the reversible limit while greatly reducing the
probability of getting trapped in a non-significant path. We also analyze the
hydrogen bond breaking within the decaalanine peptide as we force the helix into
a random coil and confirm ASMD results with less noise in the numerical averages.
PMID- 25134547
TI - Fundamental measure theory for smectic phases: scaling behavior and higher order
terms.
AB - The recent extension of Rosenfeld's fundamental measure theory to anisotropic
hard particles predicts nematic order of rod-like particles. Our analytic study
of different aligned shapes provides new insights into the structure of this
density functional, which is basically founded on experience with hard spheres.
We combine scaling arguments with dimensional crossover and motivate a modified
expression, which enables an appropriate description of smectic layering. We
calculate the nematic-smectic-A transition of monodisperse hard spherocylinders
with and without orientational degrees of freedom and present the equation of
state and phase diagram including these two liquid crystalline phases in good
agreement with simulations. We also find improved results related to the
isotropic-nematic interface. We discuss the quality of empirical corrections and
the convergence towards an exact second virial coefficient, including higher
order terms.
PMID- 25134548
TI - Analytic derivative couplings for spin-flip configuration interaction singles and
spin-flip time-dependent density functional theory.
AB - We revisit the calculation of analytic derivative couplings for configuration
interaction singles (CIS), and derive and implement these couplings for its spin
flip variant for the first time. Our algorithm is closely related to the CIS
analytic energy gradient algorithm and should be straightforward to implement in
any quantum chemistry code that has CIS analytic energy gradients. The additional
cost of evaluating the derivative couplings is small in comparison to the cost of
evaluating the gradients for the two electronic states in question. Incorporation
of an exchange-correlation term provides an ad hoc extension of this formalism to
time-dependent density functional theory within the Tamm-Dancoff approximation,
without the need to invoke quadratic response theory or evaluate third
derivatives of the exchange-correlation functional. Application to several
different conical intersections in ethylene demonstrates that minimum-energy
crossing points along conical seams can be located at substantially reduced cost
when analytic derivative couplings are employed, as compared to use of a
branching-plane updating algorithm that does not require these couplings.
Application to H3 near its D(3h) geometry demonstrates that correct topology is
obtained in the vicinity of a conical intersection involving a degenerate ground
state.
PMID- 25134549
TI - The multifacet graphically contracted function method. I. Formulation and
implementation.
AB - The basic formulation for the multifacet generalization of the graphically
contracted function (MFGCF) electronic structure method is presented. The
analysis includes the discussion of linear dependency and redundancy of the arc
factor parameters, the computation of reduced density matrices, Hamiltonian
matrix construction, spin-density matrix construction, the computation of
optimization gradients for single-state and state-averaged calculations,
graphical wave function analysis, and the efficient computation of configuration
state function and Slater determinant expansion coefficients. Timings are given
for Hamiltonian matrix element and analytic optimization gradient computations
for a range of model problems for full-CI Shavitt graphs, and it is observed that
both the energy and the gradient computation scale as O(N(2)n(4)) for N electrons
and n orbitals. The important arithmetic operations are within dense matrix
matrix product computational kernels, resulting in a computationally efficient
procedure. An initial implementation of the method is used to present
applications to several challenging chemical systems, including N2 dissociation,
cubic H8 dissociation, the symmetric dissociation of H2O, and the insertion of Be
into H2. The results are compared to the exact full-CI values and also to those
of the previous single-facet GCF expansion form.
PMID- 25134550
TI - The multifacet graphically contracted function method. II. A general procedure
for the parameterization of orthogonal matrices and its application to arc
factors.
AB - Practical algorithms are presented for the parameterization of orthogonal
matrices Q ? R(m*n) in terms of the minimal number of essential parameters {phi}.
Both square n = m and rectangular n < m situations are examined. Two separate
kinds of parameterizations are considered, one in which the individual columns of
Q are distinct, and the other in which only Span(Q) is significant. The latter is
relevant to chemical applications such as the representation of the arc factors
in the multifacet graphically contracted function method and the representation
of orbital coefficients in SCF and DFT methods. The parameterizations are
represented formally using products of elementary Householder reflector matrices.
Standard mathematical libraries, such as LAPACK, may be used to perform the basic
low-level factorization, reduction, and other algebraic operations. Some care
must be taken with the choice of phase factors in order to ensure stability and
continuity. The transformation of gradient arrays between the Q and {phi}
parameterizations is also considered. Operation counts for all factorizations and
transformations are determined. Numerical results are presented which demonstrate
the robustness, stability, and accuracy of these algorithms.
PMID- 25134551
TI - Mesodynamics with implicit degrees of freedom.
AB - Mesoscale phenomena--involving a level of description between the finest
atomistic scale and the macroscopic continuum--can be studied by a variation on
the usual atomistic-level molecular dynamics (MD) simulation technique. In
mesodynamics, the mass points, rather than being atoms, are mesoscopic in size,
for instance, representing the centers of mass of polycrystalline grains or
molecules. In order to reproduce many of the overall features of fully atomistic
MD, which is inherently more expensive, the equations of motion in mesodynamics
must be derivable from an interaction potential that is faithful to the
compressive equation of state, as well as to tensile de-cohesion that occurs
along the boundaries of the mesoscale units. Moreover, mesodynamics differs from
Newton's equations of motion in that dissipation--the exchange of energy between
mesoparticles and their internal degrees of freedom (DoFs)--must be described,
and so should the transfer of energy between the internal modes of neighboring
mesoparticles. We present a formulation where energy transfer between the
internal modes of a mesoparticle and its external center-of-mass DoFs occurs in
the phase space of mesoparticle coordinates, rather than momenta, resulting in a
Galilean invariant formulation that conserves total linear momentum and energy
(including the energy internal to the mesoparticles). We show that this approach
can be used to describe, in addition to mesoscale problems, conduction electrons
in atomic-level simulations of metals, and we demonstrate applications of
mesodynamics to shockwave propagation and thermal transport.
PMID- 25134552
TI - Sampling microcanonical ensembles of trajectories using harmonic approximation in
internal coordinates.
AB - In this paper, we modify quasiclassical harmonic sampling of microcanonical
ensembles of trajectories by using the curvilinear internal coordinates. The
harmonic approximation in the curvilinear normal coordinates provides a more
realistic description of the PES than in the conventional rectilinear ones at
finite displacements. Therefore, the sampling of vibrations in the internal
coordinates significantly improves the quality of the sampling in a block-box
fashion, providing more realistic displacements and reducing the errors in the
potential energy. In particular, the sampling of large-amplitude torsion
vibrations, which is non-realistic in the Cartesian modes, becomes accurate or
acceptable in the curvilinear modes.
PMID- 25134553
TI - Nematic-smectic transition of parallel hard spheroellipsoids.
AB - Spheroellipsoids are truncated ellipsoids with spherical end caps. If gradients
are assumed to change smoothly at the junction of body and cap, the truncation
height z0 determines the geometry uniquely. The resulting model particle has only
two shape parameters, namely, the aspect ratio c/a of the basic ellipsoid and the
cutoff z0/a. These two parameters can be tuned to yield a continuous
transformation between a pure ellipsoid and a spherocylinder. Since parallel hard
spherocylinders display a nematic-smectic A phase transition, while ellipsoids do
not, the influence of the particle shape on the possibility of a smectic phase
may be investigated. A density functional analysis is used to detect the dividing
line, in the (c/a, z0/a) plane, between the presence and absence of the N-S
transition. Since spheroellipsoids may be useful as generic model particles for
anisotropic molecules, we provide a computationally efficient overlap criterion
for a pair in a general, non-parallel configuration.
PMID- 25134554
TI - Finite-density effects in the Fredrickson-Andersen and Kob-Andersen kinetically
constrained models.
AB - We calculate the corrections to the thermodynamic limit of the critical density
for jamming in the Kob-Andersen and Fredrickson-Andersen kinetically-constrained
models, and find them to be finite-density corrections, and not finite-size
corrections. We do this by introducing a new numerical algorithm, which requires
negligible computer memory since contrary to alternative approaches, it generates
at each point only the necessary data. The algorithm starts from a single
unfrozen site and at each step randomly generates the neighbors of the unfrozen
region and checks whether they are frozen or not. Our results correspond to
systems of size greater than 10(7) * 10(7), much larger than any simulated
before, and are consistent with the rigorous bounds on the asymptotic
corrections. We also find that the average number of sites that seed a critical
droplet is greater than 1.
PMID- 25134555
TI - Theory of charge transport in molecular junctions: from Coulomb blockade to
coherent tunneling.
AB - We study charge transport through molecular junctions in the presence of electron
electron interaction using the nonequilibrium Green's function techniques and the
renormalized perturbation theory. In the perturbation treatment, the zeroth-order
Hamiltonian of the molecular junction is composed of independent single-impurity
Anderson's models, which act as the channels where charges come through or
occupy, and the interactions between different channels are treated as the
perturbation. Using this scheme, the effects of molecule-lead, electron-electron,
and hopping interactions are included nonperturbatively, and the charge transport
processes can thus be studied in the intermediate parameter range from the
Coulomb blockade to the coherent tunneling regimes. The concept of quasi
particles is introduced to describe the kinetic process of charge transport, and
then the electric current can be studied and calculated. As a test study, the
Hubbard model is used as the molecular Hamiltonian to simulate dimeric and
trimeric molecular junctions. Various nonlinear current-voltage characteristics,
including Coulomb blockade, negative differential resistance, rectification, and
current hysteresis, are shown in the calculations, and the mechanisms are
elucidated.
PMID- 25134556
TI - Computation of the memory functions in the generalized Langevin models for
collective dynamics of macromolecules.
AB - We present a numerical method to approximate the memory functions in the
generalized Langevin models for the collective dynamics of macromolecules. We
first derive the exact expressions of the memory functions, obtained from
projection to subspaces that correspond to the selection of coarse-grain
variables. In particular, the memory functions are expressed in the forms of
matrix functions, which will then be approximated by Krylov-subspace methods. It
will also be demonstrated that the random noise can be approximated under the
same framework, and the second fluctuation-dissipation theorem is automatically
satisfied. The accuracy of the method is examined through several numerical
examples.
PMID- 25134557
TI - The third-order algebraic diagrammatic construction method (ADC(3)) for the
polarization propagator for closed-shell molecules: efficient implementation and
benchmarking.
AB - The implementation of an efficient program of the algebraic diagrammatic
construction method for the polarisation propagator in third-order perturbation
theory (ADC(3)) for the computation of excited states is reported. The accuracies
of ADC(2) and ADC(3) schemes have been investigated with respect to Thiel's
recently established benchmark set for excitation energies and oscillator
strengths. The calculation of 141 vertical excited singlet and 71 triplet states
of 28 small to medium-sized organic molecules has revealed that ADC(3) exhibits
mean error and standard deviation of 0.12 +/- 0.28 eV for singlet states and
0.18 +/- 0.16 eV for triplet states when the provided theoretical best estimates
are used as benchmark. Accordingly, the ADC(2)-s and ADC(2)-x calculations
revealed accuracies of 0.22 +/- 0.38 eV and -0.70 +/- 0.37 eV for singlets and
0.12 +/- 0.16 eV and -0.55 +/- 0.20 eV for triplets, respectively. For a
comparison of CC3 and ADC(3), only non-CC3 benchmark values were considered,
which comprise 84 singlet states and 19 triplet states. For these singlet states
CC3 exhibits an accuracy of 0.23 +/- 0.21 eV and ADC(3) an accuracy of 0.08 +/-
0.27 eV, and accordingly for the triplet states of 0.12 +/- 0.10 eV and -0.10 +/-
0.13 eV, respectively. Hence, based on the quality of the existing benchmark set
it is practically not possible to judge whether ADC(3) or CC3 is more accurate,
however, ADC(3) has a much larger range of applicability due to its more
favourable scaling of O(N(6)) with system size.
PMID- 25134559
TI - An improved classical mapping method for homogeneous electron gases at finite
temperature.
AB - We introduce a modified classical mapping method to predict the exchange
correlation free energy and the structure of homogeneous electron gases (HEG) at
finite temperature. With the classical map temperature parameterized on the basis
of the quantum Monte Carlo simulation data for the correlation energy and exact
results at high and low temperature limits, the new theoretical procedure greatly
improves the classical mapping method for correlating the energetic properties
HEG over a broad range of thermodynamic conditions. Improvement can also be
identified in predicting the long-range components of the spin-averaged pair
correlation functions.
PMID- 25134558
TI - Testing procedures for extracting fluctuation spectra from lipid bilayer
simulations.
AB - To address concerns about how to obtain the height-height spectrum from
simulations of biomembranes, we emulated the fluctuations in real space using
exact input spectra. Two different methods that have given different results in
the literature were then used to extract spectra from the emulated fluctuations
that were then compared to the exact input spectra. A real space method shows
systematic, but small deviations attributed to splines introducing an artifactual
filter. A direct Fourier method obtains accurate results when the in-plane
placement of the emulated particles is uncorrelated with the out-of-plane
undulations, but systematic underestimates occur when the particle placement is
more realistically correlated with the undulations. Although quantitative
corrections cannot be estimated from our one-dimensional model, the results are
qualitatively consistent with the direct Fourier method underestimating the
1/q(2) spectral dependence that is characteristic of a tilt degree of freedom in
simulations.
PMID- 25134560
TI - Free energy of RNA-counterion interactions in a tight-binding model computed by a
discrete space mapping.
AB - The thermodynamic stability of a folded RNA is intricately tied to the
counterions and the free energy of this interaction must be accounted for in any
realistic RNA simulations. Extending a tight-binding model published previously,
in this paper we investigate the fundamental structure of charges arising from
the interaction between small functional RNA molecules and divalent ions such as
Mg(2+) that are especially conducive to stabilizing folded conformations. The
characteristic nature of these charges is utilized to construct a discretely
connected energy landscape that is then traversed via a novel application of a
deterministic graph search technique. This search method can be incorporated into
larger simulations of small RNA molecules and provides a fast and accurate way to
calculate the free energy arising from the interactions between an RNA and
divalent counterions. The utility of this algorithm is demonstrated within a
fully atomistic Monte Carlo simulation of the P4-P6 domain of the Tetrahymena
group I intron, in which it is shown that the counterion-mediated free energy
conclusively directs folding into a compact structure.
PMID- 25134561
TI - Universal scaling of potential energy functions describing intermolecular
interactions. I. Foundations and scalable forms of new generalized Mie, Lennard
Jones, Morse, and Buckingham exponential-6 potentials.
AB - Based on the formulation of the analytical expression of the potential V(r)
describing intermolecular interactions in terms of the dimensionless variables r*
= r/r(m) and E* = V/E, where r(m) is the separation at the minimum and E the well
depth, we propose more generalized scalable forms for the commonly used Mie,
Lennard-Jones, Morse, and Buckingham exponential-6 potential energy functions.
These new generalized forms have an additional parameter from the original forms
and revert to the original ones for some choice of that parameter. In this
respect, the original forms of those potentials can be considered as special
cases of the more general forms that are introduced. We also propose a scalable,
non-revertible to the original one, 4-parameter extended Morse potential.
PMID- 25134562
TI - Universal scaling of potential energy functions describing intermolecular
interactions. II. The halide-water and alkali metal-water interactions.
AB - The scaled versions of the newly introduced [S. S. Xantheas and J. C. Werhahn, J.
Chem. Phys. 141, 064117 (2014)] generalized forms of some popular potential
energy functions (PEFs) describing intermolecular interactions--Mie, Lennard
Jones, Morse, and Buckingham exponential-6--have been used to fit the ab initio
relaxed approach paths and fixed approach paths for the halide-water, X(-)(H2O),
X = F, Cl, Br, I, and alkali metal-water, M(+)(H2O), M = Li, Na, K, Rb, Cs,
interactions. The generalized forms of those PEFs have an additional parameter
with respect to the original forms and produce fits to the ab initio data that
are between one and two orders of magnitude better in the chi(2) than the
original PEFs. They were found to describe both the long-range, minimum and
repulsive wall of the respective potential energy surfaces quite accurately.
Overall the 4-parameter extended Morse (eM) and generalized Buckingham
exponential-6 (gBe-6) potentials were found to best fit the ab initio data for
these two classes of ion-water interactions. The fitted values of the parameter
of the (eM) and (gBe-6) PEFs that control the repulsive wall of the potential
correlate remarkably well with the ionic radii of the halide and alkali metal
ions.
PMID- 25134563
TI - Comparison of double-quantum NMR normalization schemes to measure homonuclear
dipole-dipole interactions.
AB - A recent implementation of a double-quantum (DQ) recoupling solid-state NMR
experiment, dubbed DQ-DRENAR, provides a quantitative measure of homonuclear
dipole-dipole coupling constants in multispin-1/2 systems. It was claimed to be
more robust than another, previously known experiment relying on the recording of
point-by-point normalized DQ build-up curves. Focusing on the POST-C7 and BaBa
xy16 DQ pulse sequences, I here present an in-depth comparison of both approaches
based upon spin-dynamics simulations, stressing that they are based upon very
similar principles and that they are largely equivalent when no imperfections are
present. With imperfections, it is found that DQ-DRENAR/POST-C7 does not fully
compensate for additional signal dephasing related to chemical shifts (CS) and
their anisotropy (CSA), which over-compensates the intrinsic CS(A)-related
efficiency loss of the DQ Hamiltonian and leads to an apparent cancellation
effect. The simulations further show that the CS(A)-related dephasing in DQ
DRENAR can be removed by another phase cycle step or an improved super-cycled
wideband version. Only the latter, or the normalized DQ build-up, are unaffected
by CS(A)-related signal loss and yield clean pure dipolar-coupling information
subject to unavoidable, pulse sequence specific performance reduction related to
higher-order corrections of the dipolar DQ Hamiltonian. The intrinsically super
cycled BaBa-xy16 is shown to exhibit virtually no CS(A) related imperfection
terms, but its dipolar performance is somewhat more challenged by CS(A) effects
than POST-C7, which can however be compensated when applied at very fast MAS (>50
kHz). Practically, DQ-DRENAR uses a clever phase cycle separation to achieve a
significantly shorter experimental time, which can also be beneficially employed
in normalized DQ build-up experiments.
PMID- 25134565
TI - Hydrogen migration in formation of NH(A3Pi) radicals via superexcited states in
photodissociation of isoxazole molecules.
AB - Formation of the excited NH(A(3)Pi) free radicals in the photodissociation of
isoxazole (C3H3NO) molecules has been studied over the 14-22 eV energy range
using photon-induced fluorescence spectroscopy. The NH(A(3)Pi) is produced
through excitation of the isoxazole molecules into higher-lying superexcited
states. Observation of the NH radical, which is not a structural unit of the
isoxazole molecule, corroborates the hydrogen atom (or proton) migration within
the molecule prior to dissociation. The vertical excitation energies of the
superexcited states were determined and the dissociation mechanisms of isoxazole
are discussed. The density functional and ab initio quantum chemical calculations
have been performed to study the mechanism of the NH formation.
PMID- 25134566
TI - Dissociation of H2 on carbon doped aluminum cluster Al6C.
AB - The dissociation of H2 molecule is the first step for chemical storage of
hydrogen, and the energy barrier of the dissociation is the key factor to decide
the kinetics of the regeneration of the storage material. As a light element,
aluminum is an important candidate component for storage materials with high
gravimetric density. This paper investigates the adsorption and dissociation of
H2 on carbon doping aluminum cluster Al6C. The study shows that doping carbon
into aluminum cluster can significantly change the electronic structure and
increase the stability. Al6C has a few stable isomers with close energies and
their structures are quite flexible. The molecular adsorption of H2 on Al6C is
very weak, but the H2 molecule can be dissociated easily on this cluster. The
stable product of the dissociated adsorption is searched and the different paths
for the dissociation are investigated. During the dissociation of H2, the
structure of the cluster adjusts accordingly, and strong orbital interaction
between the hydrogen and the cluster occurs. The calculated energy barrier for
the dissociation is only 0.30 eV, which means the dissociation can take place at
moderate temperatures.
PMID- 25134564
TI - Overhauser effects in insulating solids.
AB - We report magic angle spinning, dynamic nuclear polarization (DNP) experiments at
magnetic fields of 9.4 T, 14.1 T, and 18.8 T using the narrow line polarizing
agents 1,3-bisdiphenylene-2-phenylallyl (BDPA) dispersed in polystyrene, and
sulfonated-BDPA (SA-BDPA) and trityl OX063 in glassy glycerol/water matrices. The
(1)H DNP enhancement field profiles of the BDPA radicals exhibit a significant
DNP Overhauser effect (OE) as well as a solid effect (SE) despite the fact that
these samples are insulating solids. In contrast, trityl exhibits only a SE
enhancement. Data suggest that the appearance of the OE is due to rather strong
electron-nuclear hyperfine couplings present in BDPA and SA-BDPA, which are
absent in trityl and perdeuterated BDPA (d21-BDPA). In addition, and in contrast
to other DNP mechanisms such as the solid effect or cross effect, the
experimental data suggest that the OE in non-conducting solids scales favorably
with magnetic field, increasing in magnitude in going from 5 T, to 9.4 T, to 14.1
T, and to 18.8 T. Simulations using a model two spin system consisting of an
electron hyperfine coupled to a (1)H reproduce the essential features of the
field profiles and indicate that the OE in these samples originates from the zero
and double quantum cross relaxation induced by fluctuating hyperfine interactions
between the intramolecular delocalized unpaired electrons and their neighboring
nuclei, and that the size of these hyperfine couplings is crucial to the
magnitude of the enhancements. Microwave power dependent studies show that the OE
saturates at considerably lower power levels than the solid effect in the same
samples. Our results provide new insights into the mechanism of the Overhauser
effect, and also provide a new approach to perform DNP experiments in chemical,
biophysical, and physical systems at high magnetic fields.
PMID- 25134567
TI - Ab initio potential energy surface for methane and carbon dioxide and application
to vapor-liquid coexistence.
AB - A six-dimensional intermolecular potential energy surface for a rigid methane
(CH4) and carbon dioxide (CO2) dimer was developed from the counterpoise
corrected supermolecular approach at the CCSD(T) level of theory. A total of 466
grid points distributed to 46 orientations were calculated from the complete
basis set limit extrapolation based on up to aug-cc-pVQZ basis set. A modified
site-site pair potential function was proposed for rapid representation of the
high level ab initio calculations. A nonadditive three-body interaction was
represented by the Axilrod-Teller-Muto expression for mixtures with the
polarizability and the London dispersion constant of each molecule. Second to
fourth virial coefficients of CH4 and CO2 mixtures were calculated using both the
Mayer sampling Monte Carlo method and the present potential functions. The virial
equation of state derived from these coefficients was used to predict the pVT
values and showed good agreement with experimental data below 200 bar at 300 K.
The vapor-liquid coexistence curves of pure CH4, CO2 and their mixtures were
presented with the aid of Gibbs ensemble Monte Carlo simulations. The predicted
tie lines agreed with the experimental data within the uncertainties up to near
the critical point.
PMID- 25134568
TI - Rotational analysis of the 301 band of the A6Sigma+ <- X6Sigma+ system of CrCCH.
AB - The spectrum of chromium acetylide, CrCCH, has been investigated in the near
infrared region (10,500-14,500 cm(-1)) and an intense band system is observed.
The 301 band of this system has been investigated at high resolution (0.025 cm(
1)) and this system is identified as the A6Sigma+ <- X6Sigma+ system, analogous
to the near IR spectra of the CrH, CrF, and CrCl molecules. Among the many
unidentified lines, we have assigned 341 lines belonging to 43 of the 54 allowed
branches. Using combination differences, the rotational constants of the ground
state have been determined. Computational results on the ground state are also
reported, along with a comparison to other monoligated monovalent chromium
compounds.
PMID- 25134569
TI - Resonances in photoabsorption: predissociation line shapes in the 3ppiD1Pi(u)+ <-
X1Sigma(g)+ system in H2.
AB - The predissociation of the 3ppiD1Pi(u)+, v >= 3, N = 2, and N = 3 levels of
diatomic hydrogen is calculated by ab initio multichannel quantum defect theory
combined with a R-matrix type approach that accounts for interfering
predissociation and autoionization. The theory yields absorption line widths and
shapes that are in good agreement with those observed in the high-resolution
synchrotron vacuum-ultraviolet absorption spectra obtained by Dickenson et al.
[J. Chem. Phys. 133, 144317 (2010)] at the DESIRS beamline of the SOLEIL
synchrotron. The theory predicts further that many of the D state resonances with
v ? 6 exhibit a complex fine structure which cannot be modeled by the Fano
profile formula and which has not yet been observed experimentally.
PMID- 25134570
TI - A comparative account of quantum dynamics of the H+ + H2 reaction at low
temperature on two different potential energy surfaces.
AB - Rotationally resolved reaction probabilities, integral cross sections, and rate
constant for the H(+) + H2 (v = 0, j = 0 or 1) -> H2 (v' = 0, j') + H(+) reaction
are calculated using a time-independent quantum mechanical method and the
potential energy surface of Kamisaka et al. [J. Chem. Phys. 116, 654 (2002)] (say
KBNN PES). All partial wave contributions of the total angular momentum, J, are
included to obtain converged cross sections at low collision energies and rate
constants at low temperatures. In order to test the accuracy of the KBNN PES, the
results obtained here are compared with those obtained in our earlier work [P.
Honvault et al., Phys. Rev. Lett. 107, 023201 (2011)] using the accurate
potential energy surface of Velilla et al. [J. Chem. Phys. 129, 084307 (2008)].
Integral cross sections and rate constants obtained on the two potential energy
surfaces considered here show remarkable differences in terms of magnitude and
dependence on collision energy (or temperature) which can be attributed to the
differences observed in the topography of the surfaces near to the entrance
channel. This clearly shows the inadequacy of the KBNN PES for calculations at
low collision energies.
PMID- 25134571
TI - Interatomic Coulombic decay following resonant core excitation of Ar in argon
dimer.
AB - A scheme utilizing excitation of core electrons followed by the resonant-Auger -
interatomic Coulombic decay (RA-ICD) cascade was recently proposed as a means of
controlling the generation site and energies of slow ICD electrons. This control
mechanism was verified in a series of experiments in rare gas dimers. In this
article, we present fully ab initio computed ICD electron and kinetic energy
release spectra produced following 2p(3/2) -> 4s, 2p(1/2) -> 4s, and 2p(3/2) ->
3d core excitations of Ar in Ar2. We demonstrate that the manifold of ICD states
populated in the resonant Auger process comprises two groups. One consists of
lower energy ionization satellites characterized by fast interatomic decay, while
the other consists of slow decaying higher energy ionization satellites. We show
that accurate description of nuclear dynamics in the latter ICD states is crucial
for obtaining theoretical electron and kinetic energy release spectra in good
agreement with the experiment.
PMID- 25134572
TI - Electronic and optical properties of pure and modified diamondoids studied by
many-body perturbation theory and time-dependent density functional theory.
AB - Diamondoids are small diamond nanoparticles (NPs) that are built up from diamond
cages. Unlike usual semiconductor NPs, their atomic structure is exactly known,
thus they are ideal test-beds for benchmarking quantum chemical calculations.
Their usage in spintronics and bioimaging applications requires a detailed
knowledge of their electronic structure and optical properties. In this paper, we
apply density functional theory (DFT) based methods to understand the electronic
and optical properties of a few selected pure and modified diamondoids for which
accurate experimental data exist. In particular, we use many-body perturbation
theory methods, in the G0W0 and G0W0+BSE approximations, and time-dependent DFT
in the adiabatic local density approximation. We find large quasiparticle gap
corrections that can exceed thrice the DFT gap. The electron-hole binding energy
can be as large as 4 eV but it is considerably smaller than the GW corrections
and thus G0W0+BSE optical gaps are about 50% larger than the Kohn-Sham (KS) DFT
gaps. We find significant differences between KS time-dependent DFT and GW+BSE
optical spectra on the selected diamondoids. The calculated G0W0 quasiparticle
levels agree well with the corresponding experimental vertical ionization
energies. We show that nuclei dynamics in the ionization process can be
significant and its contribution may reach about 0.5 eV in the adiabatic
ionization energies.
PMID- 25134573
TI - Brownian aggregation rate of colloid particles with several active sites.
AB - We theoretically analyze the aggregation kinetics of colloid particles with
several active sites. Such particles (so-called "patchy particles") are well
known as chemically anisotropic reactants, but the corresponding rate constant of
their aggregation has not yet been established in a convenient analytical form.
Using kinematic approximation for the diffusion problem, we derived an analytical
formula for the diffusion-controlled reaction rate constant between two colloid
particles (or clusters) with several small active sites under the following
assumptions: the relative translational motion is Brownian diffusion, and the
isotropic stochastic reorientation of each particle is Markovian and arbitrarily
correlated. This formula was shown to produce accurate results in comparison with
more sophisticated approaches. Also, to account for the case of a low number of
active sites per particle we used Monte Carlo stochastic algorithm based on
Gillespie method. Simulations showed that such discrete model is required when
this number is less than 10. Finally, we applied the developed approach to the
simulation of immunoagglutination, assuming that the formed clusters have fractal
structure.
PMID- 25134574
TI - Spectroscopy and picosecond dynamics of aqueous NO2.
AB - We investigate the formation of aqueous nitrogen dioxide, NO2 formed through
femtosecond photolysis of nitrate, NO3- and nitromethane CH3NO2(aq). Common to
the experiments is the observation of a strong induced absorption at 1610 +/- 10
cm(-1), assigned to the asymmetric stretch vibration in the ground state of NO2.
This assignment is substantiated through isotope experiments substituting (14)N
by (15)N, experiments at different pH values, and by theoretical calculations and
simulations of NO2-D2O clusters.
PMID- 25134575
TI - The non-statistical dynamics of the 18O + 32O2 isotope exchange reaction at two
energies.
AB - The dynamics of the (18)O((3)P) + (32)O2 isotope exchange reaction were studied
using crossed atomic and molecular beams at collision energies (E(coll)) of 5.7
and 7.3 kcal/mol, and experimental results were compared with quantum statistical
(QS) and quasi-classical trajectory (QCT) calculations on the O3(X(1)A')
potential energy surface (PES) of Babikov et al. [D. Babikov, B. K. Kendrick, R.
B. Walker, R. T. Pack, P. Fleurat-Lesard, and R. Schinke, J. Chem. Phys. 118,
6298 (2003)]. In both QS and QCT calculations, agreement with experiment was
markedly improved by performing calculations with the experimental distribution
of collision energies instead of fixed at the average collision energy. At both
collision energies, the scattering displayed a forward bias, with a smaller bias
at the lower E(coll). Comparisons with the QS calculations suggest that (34)O2 is
produced with a non-statistical rovibrational distribution that is hotter than
predicted, and the discrepancy is larger at the lower E(coll). If this
underprediction of rovibrational excitation by the QS method is not due to PES
errors and/or to non-adiabatic effects not included in the calculations, then
this collision energy dependence is opposite to what might be expected based on
collision complex lifetime arguments and opposite to that measured for the
forward bias. While the QCT calculations captured the experimental product
vibrational energy distribution better than the QS method, the QCT results
underpredicted rotationally excited products, overpredicted forward-bias and
predicted a trend in the strength of forward-bias with collision energy opposite
to that measured, indicating that it does not completely capture the dynamic
behavior measured in the experiment. Thus, these results further underscore the
need for improvement in theoretical treatments of dynamics on the O3(X(1)A') PES
and perhaps of the PES itself in order to better understand and predict non
statistical effects in this reaction and in the formation of ozone (in which the
intermediate O3* complex is collisionally stabilized by a third body). The
scattering data presented here at two different collision energies provide
important benchmarks to guide these improvements.
PMID- 25134576
TI - Theoretical investigation of intersystem crossing between the a1A1 and X3B1
states of CH2 induced by collisions with helium.
AB - Collisional energy transfer between the ground (X3B1) and first excited (a1A1)
states of CH2 is facilitated by strong mixing of the rare pairs of accidentally
degenerate rotational levels in the ground vibrational manifold of the [Formula:
see text] state and the (020) and (030) excited bending vibrational manifolds of
the X state. The simplest model for this process involves coherent mixing of the
scattering T-matrix elements associated with collisional transitions within the
unmixed a and X states. From previous calculations in our group, we have
determined cross sections and room-temperature rate constants for intersystem
crossing of CH2 by collision with He. These are used in simulations of the time
dependence of the energy flow, both within and between the X and a vibronic
manifolds. Relaxation proceeds through three steps: (a) rapid equilibration of
the two mixed-pair levels, (b) fast relaxation within the a state, and (c) slower
relaxation among the levels of the X state. Collisional transfer between the fine
structure levels of the triplet (X) state is very slow.
PMID- 25134577
TI - Spectral shapes of Ar-broadened HCl lines in the fundamental band by classical
molecular dynamics simulations and comparison with experiments.
AB - Spectral shapes of isolated lines of HCl perturbed by Ar are investigated for the
first time using classical molecular dynamics simulations (CMDS). Using reliable
intermolecular potentials taken from the literature, these CMDS provide the time
evolution of the auto-correlation function of the dipole moment, whose Fourier
Laplace transform leads to the absorption spectrum. In order to test these
calculations, room temperature spectra of various lines in the fundamental band
of HCl diluted in Ar are measured, in a large pressure range, with a difference
frequency laser spectrometer. Comparisons between measured and calculated spectra
show that the CMDS are able to predict the large Dicke narrowing effect on the
shape of HCl lines and to satisfactorily reproduce the shapes of HCl spectra at
different pressures and for various rotational quantum numbers.
PMID- 25134578
TI - Theoretical predictions of properties and volatility of chlorides and
oxychlorides of group-4 elements. I. Electronic structures and properties of MCl4
and MOCl2 (M = Ti, Zr, Hf, and Rf).
AB - Relativistic, infinite order exact two-component, density functional theory
electronic structure calculations were performed for MCl4 and MOCl2 of group-4
elements Ti, Zr, Hf, and element 104, Rf, with the aim to predict their behaviour
in gas-phase chromatography experiments. RfCl4 and RfOCl2 were shown to be less
stable than their lighter homologs in the group, tetrachlorides and oxychlorides
of Zr and Hf, respectively. The oxychlorides turned out to be stable as a bent
structure, though the stabilization energy with respect to the flat one (C(2v))
is very small. The trend in the formation of the tetrachlorides from the
oxychlorides in group 4 is shown to be Zr < Hf < Rf, while the one in the
formation of the oxychlorides from the chlorides is opposite. All the calculated
properties are used to estimate adsorption energy of these species on various
surfaces in order to interpret results of gas-phase chromatography experiments,
as is shown in Paper II.
PMID- 25134579
TI - Theoretical predictions of properties and volatility of chlorides and
oxychlorides of group-4 elements. II. Adsorption of tetrachlorides and
oxydichlorides of Zr, Hf, and Rf on neutral and modified surfaces.
AB - With the aim to interpret results of gas-phase chromatography experiments on
volatility of group-4 tetrachlorides and oxychlorides including those of Rf,
adsorption enthalpies of these species on neutral, and modified quartz surfaces
were estimated on the basis of relativistic, two-component Density Functional
Theory calculations of MCl4, MOCl2, MCl6(-), and MOCl4(2) with the use of
adsorption models. Several mechanisms of adsorption were considered. In the case
of physisorption of MCl4, the trend in the adsorption energy in the group should
be Zr > Hf > Rf, so that the volatility should change in the opposite direction.
The latter trend complies with the one in the sublimation enthalpies,
DeltaH(sub), of the Zr and Hf tetrachlorides, i.e., Zr < Hf. On the basis of a
correlation between these quantities, DeltaH(sub)(RfCl4) was predicted as 104.2
kJ/mol. The energy of physisorption of MOCl2 on quartz should increase in the
group, Zr < Hf < Rf, as defined by increasing dipole moments of these molecules
along the series. In the case of adsorption of MCl4 on quartz by chemical forces,
formation of the MOCl2 or MOCl4(2-) complexes on the surface can take place, so
that the sequence in the adsorption energy should be Zr > Hf > Rf, as defined by
the complex formation energies. In the case of adsorption of MCl4 on a
chlorinated quartz surface, formation of the MCl6(2-) surface complexes can
occur, so that the trend in the adsorption strength should be Zr <= Hf < Rf. All
the predicted sequences, showing a smooth change of the adsorption energy in the
group, are in disagreement with the reversed trend Zr ~ Rf < Hf, observed in the
"one-atom-at-a-time" gas-phase chromatography experiments. Thus, currently no
theoretical explanation can be found for the experimental observations.
PMID- 25134580
TI - Vibronic coupling in asymmetric bichromophores: experimental investigation of
diphenylmethane-d5.
AB - Vibrationally and rotationally resolved electronic spectra of diphenylmethane-d5
(DPM-d5) are reported in the isolated-molecule environment of a supersonic
expansion. While small, the asymmetry induced by deuteration of one of the
aromatic rings is sufficient to cause several important effects that change the
principle mechanism of vibronic coupling between the close-lying S1 and S2
states, and spectroscopic signatures such coupling produces. The splitting
between S1 and S2 origins is 186 cm(-1), about 50% greater than its value in DPM
d0 (123 cm(-1)), and an amount sufficient to bring the S2 zero-point level into
near-resonance with the v = 1 level in the S1 state of a low-frequency phenyl
flapping mode, nu(R) = 191 cm(-1). Dispersed fluorescence spectra bear clear
evidence that Deltav(R) = 1 Herzberg-Teller coupling dominates the near-resonant
internal mixing between the S1 and S2 manifolds. The fluorescence into each pair
of Franck-Condon active ring modes shows an asymmetry that suggests incorrectly
that the S1 and S2 states may be electronically localized. From rotationally
resolved studies, the S0 and S1 states have been well-fit to asymmetric rotor
Hamiltonians while the S2 state is perturbed and not fit. The transition dipole
moment (TDM) orientation of the S1 state is nearly perpendicular to the C2
symmetry axes with 66(2)%:3(1)%:34(2)% a:b:c hybrid-type character while that of
the S2 origin contains 50(10)% a:c-type (S1) and 50(10)% b-type (S2) character. A
model is put forward that explains qualitatively the TDM compositions and
dispersed emission patterns without the need to invoke electronic localization.
The experimental data discussed here serve as a foundation for a multi-mode
vibronic coupling model capable of being applied to asymmetric bichromophores, as
presented in the work of B. Nebgen and L. V. Slipchenko ["Vibronic coupling in
asymmetric bichromophores: Theory and application to diphenylmethane-d5," J.
Chem. Phys. (submitted)].
PMID- 25134581
TI - The cyclopropene radical cation: rovibrational level structure at low energies
from high-resolution photoelectron spectra.
AB - The cyclopropene radical cation (c-C3H4+) is an important but poorly
characterized three-membered-ring hydrocarbon. We report on a measurement of the
high-resolution photoelectron and photoionization spectra of cyclopropene and
several deuterated isotopomers, from which we have determined the rovibrational
energy level structure of the X+ (2)B2 ground electronic state of c-C3H4+ at low
energies for the first time. The synthesis of the partially deuterated
isotopomers always resulted in mixtures of several isotopomers, differing in
their number of D atoms and in the location of these atoms, so that the
photoelectron spectra of deuterated samples are superpositions of the spectra of
several isotopomers. The rotationally resolved spectra indicate a C(2v)-symmetric
R0 structure for the ground electronic state of c-C3H4+. Two vibrational modes of
c-C3H4+ are found to have vibrational wave numbers below 300 cm(-1), which is
surprising for such a small cyclic hydrocarbon. The analysis of the isotopic
shifts of the vibrational levels enabled the assignment of the lowest-frequency
mode (fundamental wave number of ~110 cm(-1) in c-C3H4+) to the CH2 torsional
mode (nu8+, A2 symmetry) and of the second-lowest-frequency mode (~210 cm(-1) in
c-C3H4+) to a mode combining a CH out-of-plane with a CH2 rocking motion (nu15+,
B2 symmetry). The potential energy along the CH2 torsional coordinate is flat
near the equilibrium structure and leads to a pronounced anharmonicity.
PMID- 25134582
TI - Dispersion corrected RPBE studies of liquid water.
AB - The structure of liquid water has been addressed by ab initio molecular dynamics
simulations based on density functional theory. Exchange-correlation effects have
been described by the popular PBE and RPBE functionals within the generalized
gradient approximation as these functionals also yield satisfactory results for
metals which is important to model electrochemical interfaces from first
principles. In addition, dispersive interactions are included by using dispersion
corrected schemes. It turns out that the dispersion-corrected RPBE functional
reproduces liquid water properties quite well in contrast to the PBE functional.
This is caused by the replacement of the over-estimated directional hydrogen
bonding in the PBE functional by non-directional dispersive interactions.
PMID- 25134583
TI - Structure and aggregation in model tetramethylurea solutions.
AB - The structure of model aqueous tetramethylurea (TMU) solutions is investigated
employing large-scale (32,000, 64,000 particles) molecular dynamics simulations.
Results are reported for TMU mole fractions, X(t), ranging from infinite dilution
up to 0.07, and for two temperatures, 300 and 330 K. Two existing force fields
for TMU-water solutions are considered. These are the GROMOS 53A6 united-atom TMU
model combined with SPC/E water [TMU(GROMOS-UA)/W(SPC/E)], and the more
frequently employed AMBER03 all-atom force field for TMU combined with the TIP3P
water model [TMU(AMBER-AA)/W(TIP3P)]. It is shown that TMU has a tendency towards
aggregation for both models considered, but the tendency is significantly
stronger for the [TMU(AMBER-AA)/W(TIP3P)] force field. For this model signs of
aggregation are detected at X(t) = 0.005, aggregation is a well established
feature of the solution at X(t) = 0.02, and the aggregates increase further in
size with increasing concentration. This is in agreement with at least some
experimental studies, which report signals of aggregation in the low
concentration regime. The TMU aggregates exhibit little structure and are simply
loosely ordered, TMU-rich regions of solution. The [TMU(GROMOS-UA)/W(SPC/E)]
model shows strong signs of aggregation only at higher concentrations (X(t) ?
0.04), and the aggregates appear more loosely ordered, and less well-defined than
those occurring in the [TMU(AMBER-AA)/W(TIP3P)] system. For both models, TMU
aggregation increases when the temperature is increased from 300 to 330 K,
consistent with an underlying entropy driven, hydrophobic interaction mechanism.
At X(t) = 0.07, the extra-molecular correlation length expected for
microheterogeneous solutions has become comparable with the size of the
simulation cell for both models considered, indicating that even the systems
simulated here are sufficiently large only at low concentrations.
PMID- 25134584
TI - Properties of a planar electric double layer under extreme conditions
investigated by classical density functional theory and Monte Carlo simulations.
AB - Monte Carlo (MC) simulation and classical density functional theory (DFT) results
are reported for the structural and electrostatic properties of a planar electric
double layer containing ions having highly asymmetric diameters or valencies
under extreme concentration condition. In the applied DFT, for the excess free
energy contribution due to the hard sphere repulsion, a recently elaborated
extended form of the fundamental measure functional is used, and coupling of
Coulombic and short range hard-sphere repulsion is described by a traditional
second-order functional perturbation expansion approximation. Comparison between
the MC and DFT results indicates that validity interval of the traditional DFT
approximation expands to high ion valences running up to 3 and size asymmetry
high up to diameter ratio of 4 whether the high valence ions or the large size
ion are co- or counter-ions; and to a high bulk electrolyte concentration being
close to the upper limit of the electrolyte mole concentration the MC simulation
can deal with well. The DFT accuracy dependence on the ion parameters can be self
consistently explained using arguments of liquid state theory, and new EDL
phenomena such as overscreening effect due to monovalent counter-ions, extreme
layering effect of counter-ions, and appearance of a depletion layer with almost
no counter- and co-ions are observed.
PMID- 25134585
TI - First-principles high-pressure unreacted equation of state and heat of formation
of crystal 2,6-diamino-3, 5-dinitropyrazine-1-oxide (LLM-105).
AB - We report dispersion-corrected density functional theoretical calculations of the
unreacted equation of state (EOS) of crystal 2,6-diamino-3, 5-dinitropyrazine-1
oxide (LLM-105) under hydrostatic compression of up to 45 GPa. Convergence tests
for k-points sampling in the Brillouin zone show that a 3 * 1 * 2 mesh is
required to reproduce the X-ray crystal structure at ambient conditions, and we
confirm our finding with a separate supercell calculation. Our high-pressure EOS
yields a bulk modulus of 19.2 GPa, and indicates a tendency towards anisotropic
compression along the b lattice vector due to molecular orientations within the
lattice. We find that the electronic energy band gap decreases from a
semiconductor type of 1.3 eV at 0 GPa to quasi-metallic type of 0.6 eV at 45 GPa.
The extensive intermolecular hydrogen bonds involving the oxide (-NO) and dioxide
(-NO2) interactions with the amine (-NH2) group showed enhanced interactions with
increasing pressure that should be discernible in the mid IR spectral region. We
do not find evidence for structural phase transitions or chemically induced
transformations within the pressure range of our study. The gas phase heat of
formation is calculated at the G4 level of theory to be 22.48 kcal/mol, while we
obtain 25.92 kcal/mol using the ccCA-PS3 method. Density functional theory
calculations of the crystal and the gas phases provided an estimate for the heat
of sublimation of 32.4 kcal/mol. We thus determine the room-temperature solid
heat of formation of LLM-105 to be -9.9 or -6.5 kcal/mol based on the G4 or ccCA
PS3 methods, respectively.
PMID- 25134586
TI - Challenges in first-principles NPT molecular dynamics of soft porous crystals: a
case study on MIL-53(Ga).
AB - Soft porous crystals present a challenge to molecular dynamics simulations with
flexible size and shape of the simulation cell (i.e., in the NPT ensemble), since
their framework responds very sensitively to small external stimuli. Hence, all
interactions have to be described very accurately in order to obtain correct
equilibrium structures. Here, we report a methodological study on the nanoporous
metal-organic framework MIL-53(Ga), which undergoes a large-amplitude transition
between a narrow- and a large-pore phase upon a change in temperature. Since this
system has not been investigated by density functional theory (DFT)-based NPT
simulations so far, we carefully check the convergence of the stress tensor with
respect to computational parameters. Furthermore, we demonstrate the importance
of dispersion interactions and test two different ways of incorporating them into
the DFT framework. As a result, we propose two computational schemes which
describe accurately the narrow- and the large-pore phase of the material,
respectively. These schemes can be used in future work on the delicate interplay
between adsorption in the nanopores and structural flexibility of the host
material.
PMID- 25134588
TI - Point defect weakened thermal contraction in monolayer graphene.
AB - We investigate the thermal expansion behaviors of monolayer graphene and three
configurations of graphene with point defects, namely the replacement of one
carbon atom with a boron or nitrogen atom, or of two neighboring carbon atoms by
boron-nitrogen atoms, based on calculations using first-principles density
functional theory. It is found that the thermal contraction of monolayer graphene
is significantly decreased by point defects. Moreover, the corresponding
temperature for negative linear thermal expansion coefficient with the maximum
absolute value is reduced. The cause is determined to be point defects that
enhance the mechanical strength of graphene and then reduce the amplitude and
phonon frequency of the out-of-plane acoustic vibration mode. Such defect
weakening of graphene thermal contraction will be useful in nanotechnology to
diminish the mismatching or strain between the graphene and its substrate.
PMID- 25134587
TI - Lateral critical Casimir force in 2D Ising strip with inhomogeneous walls.
AB - We analyze the lateral critical Casimir force acting between two planar,
chemically inhomogeneous walls confining an infinite 2D Ising strip of width M.
The inhomogeneity of each of the walls has size N1; they are shifted by the
distance L along the strip. Using the exact diagonalization of the transfer
matrix, we calculate the lateral critical Casimir force and discuss its
properties, in particular its scaling close to the 2D bulk critical point, as a
function of temperature, surface magnetic field, and the geometric parameters M,
N1, L. We determine the magnetization profiles which display the formation of the
bridge joining the inhomogeneities on the walls and establish the relation
between the characteristic properties of the lateral Casimir force and
magnetization morphologies. We check numerically that breaking of the bridge is
related to the inflection point of the lateral force.
PMID- 25134589
TI - Lone-pair interactions and photodissociation of compressed nitrogen trifluoride.
AB - High-pressure behavior of nitrogen trifluoride (NF3) was investigated by Raman
and IR spectroscopy at pressures up to 55 GPa and room temperature, as well as by
periodic calculations up to 100 GPa. Experimentally, we find three solid-solid
phase transitions at 9, 18, and 39.5 GPa. Vibrational spectroscopy indicates that
in all observed phases NF3 remains in the molecular form, in contrast to the
behavior of compressed ammonia. This finding is confirmed by density functional
theory calculations, which also indicate that the phase transitions of compressed
NF3 are governed by the interplay between lone-pair interactions and efficient
molecule packing. Although nitrogen trifluoride is molecular in the whole
pressure range studied, we show that it can be photodissociated by mid-IR laser
radiation. This finding paves the way for the use of NF3 as an oxidizing and
fluorinating agent in high-pressure reactions.
PMID- 25134590
TI - Tunable electronic and optical properties of monolayer silicane under tensile
strain: a many-body study.
AB - The electronic structure and optical response of silicane to strain are
investigated by employing first-principles calculations based on many-body
perturbation theory. The bandgap can be efficiently engineered in a broad range
and an indirect to direct bandgap transition is observed under a strain of 2.74%;
the semiconducting silicane can even be turned into a metal under a very large
strain. The transitions derive from the persistent downward shift of the lowest
conduction band at the Gamma-point upon an increasing strain. The quasi-particle
bandgaps of silicane are sizable due to the weak dielectric screening and the low
dimension; they are rapidly reduced as strain increases while the exciton bound
energy is not that sensitive. Moreover, the optical absorption edge of the
strained silicane significantly shifts towards a low photon energy region and
falls into the visible light range, which might serve as a promising candidate
for optoelectronic devices.
PMID- 25134591
TI - Hydrogen adsorption in metal-organic frameworks: the role of nuclear quantum
effects.
AB - The role of nuclear quantum effects on the adsorption of molecular hydrogen in
metal-organic frameworks (MOFs) has been investigated on grounds of Grand
Canonical Quantized Liquid Density-Functional Theory (GC-QLDFT) calculations. For
this purpose, we have carefully validated classical H2-host interaction
potentials that are obtained by fitting Born-Oppenheimer ab initio reference
data. The hydrogen adsorption has first been assessed classically using Liquid
Density-Functional Theory and the Grand-Canonical Monte Carlo methods. The
results have been compared against the semi-classical treatment of quantum
effects by applying the Feynman-Hibbs correction to the Born-Oppenheimer-derived
potentials, and by explicit treatment within the GC-QLDFT. The results are
compared with experimental data and indicate pronounced quantum and possibly many
particle effects. After validation calculations have been carried out for IRMOF-1
(MOF-5), GC-QLDFT is applied to study the adsorption of H2 in a series of MOFs,
including IRMOF-4, -6, -8, -9, -10, -12, -14, -16, -18, and MOF-177. Finally, we
discuss the evolution of the H2 quantum fluid with increasing pressure and
lowering temperature.
PMID- 25134592
TI - Density functional theory study of CO-induced segregation in gold-based alloys.
AB - This paper reports a systematic study of the effect of CO gas on the chemical
composition at the surface of gold-based alloys. Using DFT periodic calculations
in presence of adsorbed CO the segregation behavior of group 9-10-11 transition
metals (Ag, Cu, Pt, Pd, Ni, Ir, Rh, Co) substituted in semi-infinite gold
surfaces is investigated. Although, CO is found to be more strongly adsorbed on
(100) than on the (111) surface, the segregation of M impurities is found to be
more pronounced on the (111) surface. The results reveal two competitive effects:
the effect of M on CO and the effect of CO on M. Thus, on one hand, if M exists
on the (100) gold facet, CO would be strongly adsorbed on it. But if M is
initially located in the bulk, it would segregate to the (111) facet instead of
the (100) in order to bind to CO.
PMID- 25134593
TI - Multi-scale times and modes of fast and slow relaxation in solutions with
coexisting spherical and cylindrical micelles according to the difference Becker
Doring kinetic equations.
AB - The eigenvalues and eigenvectors of the matrix of coefficients of the linearized
kinetic equations applied to aggregation in surfactant solution determine the
full spectrum of characteristic times and specific modes of micellar relaxation.
The dependence of these relaxation times and modes on the total surfactant
concentration has been analyzed for concentrations in the vicinity and well above
the second critical micelle concentration (cmc2) for systems with coexisting
spherical and cylindrical micelles. The analysis has been done on the basis of a
discrete form of the Becker-Doring kinetic equations employing the Smoluchowsky
diffusion model for the attachment rates of surfactant monomers to surfactant
aggregates with matching the rates for spherical aggregates and the rates for
large cylindrical micelles. The equilibrium distribution of surfactant aggregates
in solution has been modeled as having one maximum for monomers, another maximum
for spherical micelles and wide slowly descending branch for cylindrical
micelles. The results of computations have been compared with the analytical ones
known in the limiting cases from solutions of the continuous Becker-Doring
kinetic equation. They demonstrated a fair agreement even in the vicinity of the
cmc2 where the analytical theory looses formally its applicability.
PMID- 25134594
TI - Simulation of electric double layers around charged colloids in aqueous solution
of variable permittivity.
AB - The ion distribution around charged colloids in solution has been investigated
intensely during the last decade. However, few theoretical approaches have
included the influence of variation in the dielectric permittivity within the
system, let alone in the surrounding solvent. In this article, we introduce two
relatively new methods that can solve the Poisson equation for systems with
varying permittivity. The harmonic interpolation method approximately solves the
Green's function in terms of a spherical harmonics series, and thus provides
analytical ion-ion potentials for the Hamiltonian of charged systems. The Maxwell
equations molecular dynamics algorithm features a local approach to
electrostatics, allowing for arbitrary local changes of the dielectric constant.
We show that the results of both methods are in very good agreement. We also
found that the renormalized charge of the colloid, and with it the effective far
field interaction, significantly changes if the dielectric properties within the
vicinity of the colloid are changed.
PMID- 25134595
TI - Bilayer registry in a multicomponent asymmetric membrane: dependence on lipid
composition and chain length.
AB - A question of considerable interest to cell membrane biology is whether phase
segregated domains across an asymmetric bilayer are strongly correlated with each
other and whether phase segregation in one leaflet can induce segregation in the
other. We answer both these questions in the affirmative, using an atomistic
molecular dynamics simulation to study the equilibrium statistical properties of
a 3-component asymmetric lipid bilayer comprising an unsaturated palmitoyl-oleoyl
phosphatidyl-choline, a saturated sphingomyelin, and cholesterol with different
composition ratios. Our simulations are done by fixing the composition of the
upper leaflet to be at the coexistence of the liquid ordered (l(o))-liquid
disordered (l(d)) phases, while the composition of the lower leaflet is varied
from the phase coexistence regime to the mixed l(d) phase, across a first-order
phase boundary. In the regime of phase coexistence in each leaflet, we find
strong transbilayer correlations of the l(o) domains across the two leaflets,
resulting in bilayer registry. This transbilayer correlation depends sensitively
upon the chain length of the participating lipids and possibly other features of
lipid chemistry, such as degree of saturation. We find that the l(o) domains in
the upper leaflet can induce phase segregation in the lower leaflet, when the
latter is nominally in the mixed (l(d)) phase.
PMID- 25134596
TI - Molar mass and temperature dependence of the thermodiffusion of polyethylene
oxide in water/ethanol mixtures.
AB - In this work, we study the molar mass dependence of the thermodiffusion of
polyethylene oxide at different temperatures in ethanol, water/ethanol mixture
(c(water) = 0.7), and water in a molar mass range up to M(w) = 180,000 g/mol. Due
to the low solubility of polyethylene oxide oligomers in ethanol the measurements
are limited up to M(w) = 2200 g/mol. The specific water/ethanol concentration 0.7
has been chosen, because at this weight fraction the thermal diffusion
coefficient, D(T), of water/ethanol vanishes so that the system can be treated as
a pseudo binary mixture. The addition of ethanol will degrade the solvent
quality, so that we expect a change of the interaction energies between polymer
and solvent. The analysis of the experimental data within a theoretical model
shows the need of a refined model, which takes specific interactions into
account.
PMID- 25134597
TI - Isolating the non-polar contributions to the intermolecular potential for water
alkane interactions.
AB - Intermolecular potential models for water and alkanes describe pure component
properties fairly well, but fail to reproduce properties of water-alkane
mixtures. Understanding interactions between water and non-polar molecules like
alkanes is important not only for the hydrocarbon industry but has implications
to biological processes as well. Although non-polar solutes in water have been
widely studied, much less work has focused on water in non-polar solvents. In
this study we calculate the solubility of water in different alkanes (methane to
dodecane) at ambient conditions where the water content in alkanes is very low so
that the non-polar water-alkane interactions determine solubility. Only the
alkane-rich phase is simulated since the fugacity of water in the water rich
phase is calculated from an accurate equation of state. Using the SPC/E model for
water and TraPPE model for alkanes along with Lorentz-Berthelot mixing rules for
the cross parameters produces a water solubility that is an order of magnitude
lower than the experimental value. It is found that an effective water Lennard
Jones energy epsilon(W)/k = 220 K is required to match the experimental water
solubility in TraPPE alkanes. This number is much higher than used in most
simulation water models (SPC/E-epsilon(W)/k = 78.2 K). It is surprising that the
interaction energy obtained here is also higher than the water-alkane interaction
energy predicted by studies on solubility of alkanes in water. The reason for
this high water-alkane interaction energy is not completely understood. Some
factors that might contribute to the large interaction energy, such as
polarizability of alkanes, octupole moment of methane, and clustering of water at
low concentrations in alkanes, are examined. It is found that, though important,
these factors do not completely explain the anomalously strong attraction between
alkanes and water observed experimentally.
PMID- 25134598
TI - Rotational Brownian dynamics simulations of clathrin cage formation.
AB - The self-assembly of nearly rigid proteins into ordered aggregates is well suited
for modeling by the patchy particle approach. Patchy particles are traditionally
simulated using Monte Carlo methods, to study the phase diagram, while Brownian
Dynamics simulations would reveal insights into the assembly dynamics. However,
Brownian Dynamics of rotating anisotropic particles gives rise to a number of
complications not encountered in translational Brownian Dynamics. We thoroughly
test the Rotational Brownian Dynamics scheme proposed by Naess and Elsgaeter
[Macromol. Theory Simul. 13, 419 (2004); Naess and Elsgaeter Macromol. Theory
Simul. 14, 300 (2005)], confirming its validity. We then apply the algorithm to
simulate a patchy particle model of clathrin, a three-legged protein involved in
vesicle production from lipid membranes during endocytosis. Using this algorithm
we recover time scales for cage assembly comparable to those from experiments. We
also briefly discuss the undulatory dynamics of the polyhedral cage.
PMID- 25134599
TI - The role of non-equilibrium fluxes in the relaxation processes of the linear
chemical master equation.
AB - We propose a non-equilibrium thermodynamical description in terms of the Chemical
Master Equation (CME) to characterize the dynamics of a chemical cycle chain
reaction among m different species. These systems can be closed or open for
energy and molecules exchange with the environment, which determines how they
relax to the stationary state. Closed systems reach an equilibrium state
(characterized by the detailed balance condition (D.B.)), while open systems will
reach a non-equilibrium steady state (NESS). The principal difference between
D.B. and NESS is due to the presence of chemical fluxes. In the D.B. condition
the fluxes are absent while for the NESS case, the chemical fluxes are necessary
for the state maintaining. All the biological systems are characterized by their
"far from equilibrium behavior," hence the NESS is a good candidate for a
realistic description of the dynamical and thermodynamical properties of living
organisms. In this work we consider a CME written in terms of a discrete
Kolmogorov forward equation, which lead us to write explicitly the non
equilibrium chemical fluxes. For systems in NESS, we show that there is a non
conservative "external vector field" whose is linearly proportional to the
chemical fluxes. We also demonstrate that the modulation of these external fields
does not change their stationary distributions, which ensure us to study the same
system and outline the differences in the system's behavior when it switches from
the D.B. regime to NESS. We were interested to see how the non-equilibrium fluxes
influence the relaxation process during the reaching of the stationary
distribution. By performing analytical and numerical analysis, our central result
is that the presence of the non-equilibrium chemical fluxes reduces the
characteristic relaxation time with respect to the D.B. condition. Within a
biochemical and biological perspective, this result can be related to the
"plasticity property" of biological systems and to their capabilities to switch
from one state to another as is observed during synaptic plasticity, cell fate
determination, and differentiation.
PMID- 25134604
TI - A comparison of risk factors for hepatitis C among young and older adult
prisoners.
AB - Internationally, the prevalence of hepatitis C infection is higher among
prisoners when compared to the general population, particularly among people who
inject drugs. This study estimates the prevalence of, and compares the risk
factors for, hepatitis C in young (< 25 years) and older (>= 25 years) prisoners
with a history of injection drug use. Participants were 677 sentenced prisoners
in Queensland, Australia, with a lifetime history of injection drug use,
recruited in the 6 weeks prior to release from custody. The prevalence of
hepatitis C exposure was significantly lower in young prisoners than in older
prisoners (20.7% vs. 29.4%, p = .03). Risk factors for hepatitis C varied between
young and older prisoners. Young people who inject drugs and who have had shorter
time at risk of hepatitis C exposure are an important target group for hepatitis
C prevention efforts.
PMID- 25134605
TI - Observation of a rare earth ion-extractant complex arrested at the oil-water
interface during solvent extraction.
AB - Selective extraction of metal ions from a complex aqueous mixture into an organic
phase is used to separate toxic or radioactive metals from polluted environments
and nuclear waste, as well as to produce industrially relevant metals, such as
rare earth ions. Selectivity arises from the choice of an extractant amphiphile,
dissolved in the organic phase, which interacts preferentially with the target
metal ion. The extractant-mediated process of ion transport from an aqueous to an
organic phase takes place at the aqueous-organic interface; nevertheless, little
is known about the molecular mechanism of this process despite its importance.
Although state-of-the-art X-ray scattering is uniquely capable of probing
molecular ordering at a liquid-liquid interface with subnanometer spatial
resolution, utilizing this capability to investigate interfacial dynamical
processes of short temporal duration remains a challenge. We show that a
temperature-driven adsorption transition can be used to turn the extraction on
and off by controlling adsorption and desorption of extractants at the oil-water
interface. Lowering the temperature through this transition immobilizes a
supramolecular ion-extractant complex at the interface during the extraction of
rare earth erbium ions. Under the conditions of these experiments, the ion
extractant complexes condense into a two-dimensional inverted bilayer, which is
characterized on the molecular scale with synchrotron X-ray reflectivity and
fluorescence measurements. Raising the temperature above the transition leads to
Er ion extraction as a result of desorption of ion-extractant complexes from the
interface into the bulk organic phase. XAFS measurements of the ion-extractant
complexes in the bulk organic phase demonstrate that they are similar to the
interfacial complexes.
PMID- 25134606
TI - Interfacial load transfer in polymer/carbon nanotube nanocomposites with a
nanohybrid shish kebab modification.
AB - Interfacial properties are known to have a critical effect on the mechanical
properties of a nanocomposite material system. Here, the interfacial load
transfer in a carbon nanotube (CNT)/nylon-11 composite was studied with a
CNT/nylon-11 nanohybrid shish kebab (NHSK) structure modification using Raman
spectroscopy. Characterization of the polymer crystal in the NHSK using
differential scanning calorimetry (DSC) for the first time indicates that the
NHSK structure formed a more perfect crystal structure than the bulk polymer. On
the basis of transmission electron microscopy and DSC results, a new growth model
for the NHSK crystal is hypothesized, indicating the formation of an initial
uniform crystal layer on the CNT prior to the crystallization of the kebabs.
Characterization of the nanocomposites using Raman spectroscopy, with the samples
heated to introduce interfacial shear stress caused by thermal expansion
mismatch, found that the D* band of the CNT in the NHSK/nylon-11 composite
displayed a more pronounced shift with an increase in temperature, which is
attributed to the NHSK structure being more effective at transferring load from
the nylon matrix to the nanotube inclusions. The NHSK structure was also used to
fabricate composites with two amorphous polymers, polycarbonate and poly(methyl
methacrylate), to investigate the load transfer mechanism. It was found that when
the compatibility between the polymer in the NHSK structure and the bulk polymer
matrix at the molecular level is sufficiently high, the ensuing mechanical
interlocking effect further enhances the interfacial load transfer for polymer
nanocomposites. Additional mechanical characterization of polymer nanocomposites
with 0.1 wt % NHSK reinforcement demonstrates how the moduli and ultimate tensile
strength of the nanocomposites can be improved via this NHSK structure.
PMID- 25134609
TI - An-jun-ning, a traditional herbal formula, attenuates spontaneous withdrawal
symptoms via modulation of the dopamine system in morphine-dependent rats.
AB - BACKGROUND: The dopamine system, which is involved in drug dependence, can be
damaged by opioid abuse. However, current clinical medicines cannot reverse these
damages in the brain, which are believed to be a key reason for the high relapse
rate after abstinence treatment. This study aimed to investigate the effects of
An-jun-ning (AJN), a commercial traditional Chinese medicine formula used for the
treatment of opioid addiction, on the dopamine system in morphine-dependent rats
and to explore the possible mechanism underlying its therapeutic effects.
METHODS: The morphine dependence model was obtained through injections of
morphine at increasing doses for 8 days. The AJN pre-treatment group was
administered AJN 30 min before each morphine administration, and the AJN post
treatment groups were treated with AJN for 10 days after withdrawal. Spontaneous
withdrawal symptoms (wet dog shakes, and episodes of writhing) were observed
after withdrawal. Autoradiography study and/or immunohistochemical staining were
used to examine the levels of dopamine transporter (DAT), dopamine D2 receptor
(D2R) and tyrosine hydroxylase (TH). RESULTS: (1) Pre-treatment with AJN
attenuates wet dog shakes and episodes of writhing to approximately 50% or less
of those observed in the morphine group (p < 0.01). (2) AJN post-treatment dose
dependently reduced the number of wet dog shakes (p < 0.01), and the episodes of
writhing (p < 0.01). (3) Pre-treatment with AJN effectively interdicted the
morphine-induced decreases in the levels of DAT, D2R, and TH in the striatum (p <
0.01) such that they remained at nearly normal levels. (4) Post-treatment with
AJN restored DAT and D2R to the normal levels (p < 0.01) and the level of TH to
87% of normal in the striatum. CONCLUSIONS: AJN can effectively alleviate opioid
withdrawal symptoms and preserve or restore the DAT, D2R, and TH levels in the
striatum. The mechanism underlying the effect of AJN on withdrawal symptoms may
be related to the modulation of the dopamine system by AJN. These results suggest
that AJN may help to prevent relapse in opioid dependence treatment.
PMID- 25134619
TI - Host response: new LPS receptors discovered.
PMID- 25134617
TI - Interplay between phosphorylation and SUMOylation events determines CESTA protein
fate in brassinosteroid signalling.
AB - Brassinosteroids (BRs) are steroid hormones that are essential for plant growth.
Responses to these hormones are mediated by transcription factors of the bri1-EMS
suppressor 1/brassinazole resistant 1 subfamily, and BRs activate these factors
by impairing their inhibitory phosphorylation by GSK3/shaggy-like kinases. Here
we show that BRs induce nuclear compartmentalization of CESTA (CES), a basic
helix-loop-helix transcription factor that regulates BR responses, and reveal
that this process is regulated by CES SUMOylation. We demonstrate that CES
contains an extended SUMOylation motif, and that SUMOylation of this motif is
antagonized by phosphorylation to control CES subnuclear localization. Moreover,
we provide evidence that phosphorylation regulates CES transcriptional activity
and protein turnover by the proteasome. A coordinated modification model is
proposed in which, in a BR-deficient situation, CES is phosphorylated to activate
target gene transcription and enable further posttranslational modification that
controls CES protein stability and nuclear dynamics.
PMID- 25134618
TI - Master recyclers: features and functions of bacteria associated with
phytoplankton blooms.
AB - Marine phytoplankton blooms are annual spring events that sustain active and
diverse bloom-associated bacterial populations. Blooms vary considerably in terms
of eukaryotic species composition and environmental conditions, but a limited
number of heterotrophic bacterial lineages - primarily members of the
Flavobacteriia, Alphaproteobacteria and Gammaproteobacteria - dominate these
communities. In this Review, we discuss the central role that these bacteria have
in transforming phytoplankton-derived organic matter and thus in biogeochemical
nutrient cycling. On the basis of selected field and laboratory-based studies of
flavobacteria and roseobacters, distinct metabolic strategies are emerging for
these archetypal phytoplankton-associated taxa, which provide insights into the
underlying mechanisms that dictate their behaviours during blooms.
PMID- 25134620
TI - A systematic review on the affordability of a healthful diet for families in the
United States.
AB - OBJECTIVES: As obesity rates remain alarmingly high, the importance of healthful
diets is emphasized; however, affordability of such diets is disputed. Market
basket surveys (MBSs) investigate the affordability of diets for families that
meet minimum daily dietary requirements using actual food prices from grocery
stores. This review paper describes the methods of MBSs, summarizes methodology,
price and affordability findings, limitations, and suggests related policy and
practice implications. DESIGN AND SAMPLE: This is a systematic review of 16 MBSs
performed in the United States from 1985 to 2012. A comprehensive
multidisciplinary database search strategy was used to identify articles meeting
inclusion criteria. RESULTS: Results indicated MBS methodology varied across
studies and price data indicated healthful diets for families are likely
unaffordable when purchased from small- to medium-sized stores and may be
unaffordable in larger stores when compared to the Thrifty Food Plan.
CONCLUSIONS: Using a social ecological approach, public health nurses and all
public health professionals are prime advocates for increased affordability of
healthful foods. This study includes policy advocacy, particularly in support of
Supplemental Nutrition Assistance Program benefits for low-income families.
Future research implications are provided, including methodological
recommendations for consistency and quality of forthcoming MBS research.
PMID- 25134621
TI - Comparison of programs for determining temporal-spatial gait variables from
instrumented walkway data: PKmas versus GAITRite.
AB - BACKGROUND: Measurement of temporal-spatial gait variables is common in aging
research with several methods available. This study investigated the differences
in temporal-spatial gait outcomes derived from two different programs for
processing instrumented walkway data. METHOD: Data were collected with
GAITRite(r) hardware from 86 healthy older people and 44 older people four months
following surgical repair of hip fracture. Temporal-spatial variables were
derived using both GAITRite(r) and PKmas(r) processing programs from the same raw
footfall data. RESULTS: The mean differences between the two programs for most
variables were negligible, including for Speed (mean difference 0.3 +/- 0.6
cm/sec, or 0.3% of the mean GAITRite(r) Speed). The mean absolute percentage
difference for all 18 gait variables examined ranged from 0.04% for Stride
Duration to 66% for Foot Angle. The ICCs were almost perfect (>=0.99) for all
variables apart from Base Width, Foot Angle, Stride Length Variability, Step
Length Variability, Step Duration Variability and Step Width Variability, which
were all never-the-less above 0.84. There were systematic differences for Base
Width (PKmas(r) values 1.6 cm lower than GAITRite(r)) and Foot Angle (PKMAS(r)
values 0.7 degrees higher than GAITRite(r)). The differences can be explained by
the differences in definitions and calculations between the programs.
CONCLUSIONS: The study demonstrated that for most variables the outcomes from
both programs can be used interchangeably for evaluation of gait among older
people collected with GAITRite(r) hardware. However, validity and reliability for
Base Width and Foot Angle derived by PKMAS(r) would benefit from further
investigation.
PMID- 25134622
TI - Positive and negative experiences of breast pumping during the first 6 months.
AB - For mothers with breastfeeding difficulties, pumping can be recommended to help
establish milk production. However, pumping may present some barriers to
successful breastfeeding. Mothers with milk supply concern may be at higher risk
of barriers to successful breastfeeding. No previous studies have described
experiences of pumping among mothers with milk supply concern. We conducted 10
focus groups of 56 mothers who had milk supply concern in the first month after
birth. A paid, trained facilitator led groups in a semi-structured approach.
Sessions were audiorecorded and transcribed verbatim. The transcripts were coded
independently by two investigators and analysed using grounded theory. We
identified five themes related to the experience of pumping among mothers with
milk supply concern: (1) additional control over breastfeeding from pumping: 'I
would feed and then give him ... whatever I could manage to pump to him'. (2)
Painful experience: 'The first time I pumped my boobs hurt so bad'. (3) Pumped
volume affected milk supply concern: 'Pump and there was hardly anything coming
out that's when I started to worry'. (4) Pumping interfered with other nurturing
activities: 'While you're pumping, you can't touch the baby'. (5) Frustration
from inconsistent provider advice: 'They told me to pump ... and then said,
"That's going to cause your milk to increase too much" '. Mothers had positive
and negative experiences with pumping. Clinicians should assess a mother's
experience shortly after she initiates pumping, as further management and
counselling may be necessary to avoid barriers to successful breastfeeding.
PMID- 25134623
TI - Calcium supplementation in chronic kidney disease.
AB - INTRODUCTION: There is high prevalence of calcium supplementation in the general
population and some recent data suggest that this may increase the risk of
vascular calcification. Calcium-based binders have been a standard treatment for
hyperphosphatemia in patients with chronic kidney disease (CKD). Though as
effective as phosphate binders, they provide a source of substantial calcium
intake. AREAS COVERED: In addition to the balance studies recently completed to
assess the implications of calcium loading in CKD, we also review observational
studies and clinical trials involving calcium-based binders. Clinically
significant endpoints such as vascular calcification, mortality and bone
morphology were evaluated. The existing data are concerning for the role of
calcium supplementation and calcium binder use in patients with renal compromise.
EXPERT OPINION: There are few guidelines on advised calcium intake in patients
with renal failure; however, on the basis of existing data, it may be safer to
have the upper limit of calcium intake (including that of supplementation/binder
use) up to 1 g. The old Kidney Disease Outcomes Quality Initiative suggestion of
limiting the calcium intake to 2 g may need to be reconsidered.
PMID- 25134624
TI - Author's response.
PMID- 25134625
TI - Autonomous basin climbing method with sampling of multiple transition pathways:
application to anisotropic diffusion of point defects in hcp Zr.
AB - This paper presents an extension of the autonomous basin climbing (ABC) method,
an atomistic activation-relaxation technique for sampling transition-state
pathways. The extended algorithm (ABC-E) allows the sampling of multiple
transition pathways from a given minimum, with the additional feature of
identifying the pathways in the order of increasing activation barriers, thereby
prioritizing them according to their importance in the kinetics. Combined with on
the-fly kinetic Monte Carlo calculations, the method is applied to simulate the
anisotropic diffusion of point defects in hcp Zr. Multiple migration mechanisms
are identified for both the interstitials and vacancies, and benchmarked against
results from other methods in the literature. The self-interstitial atom (SIA)
diffusion kinetics shows a maximum anisotropy at intermediate temperatures
(400~700 K), a non-monotonic behavior that we explain to originate from the
stabilities and migration mechanisms associated with different SIA sites. The
accuracy of the ABC-E calculations is validated, in part, by the existing results
in the literature for point defect diffusion in hcp Zr, and by benchmarking
against analytical results on a hypothetical rough-energy landscape. Lastly,
sampling prioritization and computational efficiency are demonstrated through a
direct comparison between the ABC-E and the activation relaxation technique.
PMID- 25134626
TI - Anomalous orientations of a rigid carbon nanotube in a sheared fluid.
AB - The nanoparticle orientation in fluid systems can be correlated with the
rotational diffusion and is widely used to tune the physical properties of
functional materials. In the current work, the controllability of the orientation
of a single rigid carbon nanotube in a fluid is investigated by imposing a linear
shear flow. Molecular dynamics simulations reveal three forms of anomalous
behavior: (i) "Aligned orientation" when the nanotube oscillates around a
particular direction which is close to the flow direction at a small angle of
about 10 degrees in the velocity-gradient plane; (ii) "Interrupted orientation"
when the oscillation is interrupted by a 360 degrees rotation now and then;
(iii) "Random orientation" when 360 degrees rotations dominate with the
rotational direction coinciding with the local fluid flow direction. The
orientation order is a function of the Peclet number (Pe). The results show that
the correlation between Pe and the orientation order from the two-dimensional
model does not apply to the three-dimensional cases, perhaps due to some
anomalous behavior and cross-section effects. This work provides clear pictures
of the nanoparticle movement that can be used to guide particle manipulation
techniques.
PMID- 25134628
TI - [Working conditions for supermarket employees: from experimental data to best
practices].
AB - BACKGROUND: Thermal, acoustic and visual comfort conditions for hypermarket
workers have never been investigated with scientific methods. OBJECTIVES: taking
advantage of a case study, with characteristics capable of generalizing the
results, analytically measure the actual comfort conditions to which workers are
exposed and point out possible ameliorative proposals. METHODS: Carry out a
detailed survey based on instrumental measurements combined with subjective
questionnaires to assess the indoor environment. RESULTS: Even though the
analysis pointed out no significant risk conditions, several smaller problems
appeared in terms of local discomfort (such as cold limbs, higher sound level
exposure, limited glare phenomena) for cashier workers. The origin of these
problems appeared to be the pivotal position of the cash registers. CONCLUSIONS:
Taking into account observed phenomena and their causes a list of "best
practices" has been defined hoping that their adoption could further limit any
impact on workers comfort conditions.
PMID- 25134630
TI - [Musculoskeletal disorders and work-related injuries among hospital day- and
shift workers].
AB - BACKGROUND: Most research findings show that shift-and night work are associated
with cardiovascular, musculoskeletal and neurological disorders as well as work
related injuries among health care workers. OBJECTIVES: This sample based study
on 246 hospital workers was performed to determine whether shift work may affect
musculoskeletal disorders and injury risk. METHODS: During the health
surveillance program, data were collected by means of the Nordic questionnaire
and the risk evaluation document. RESULTS AND CONCLUSIONS: A sample of 134 shift
workers was compared to a sample of 112 day workers. Hospital day workers were
found to be at greater risk of musculoskeletal symptoms in single or multiple
body sites than shift workers. The prevalence of symptoms in the low back (63% vs
50%), neck (54% vs 42%) and upper extremities (26% vs 12%) was significantly
higher in day workers than shift workers. In particular, among day nurses the
prevalence of complaints in the upper extremities was more elevated (p<0,01) than
nurses working in shifts; whereas, technicians working during the day reported
more frequently symptoms in the neck (p<0,05) than technicians working in shifts.
However, the average age and work experience were significantly higher in day
workers than shift workers. Furthermore, the study showed that nursing personnel
was at great risk of sustaining an occupational musculoskeletal injury,
especially for nurses working in shifts on medical and surgical wards. Data
suggest that, concerning shift work planning, it is important to consider the
workload according to activity.
PMID- 25134629
TI - A rare occupation causing mesothelioma: mechanisms and differential etiology.
AB - BACKGROUND: In a mesothelioma lawsuit, the Public Prosecutor commissioned an
expert evidence on the legal accountability for the disease, because the patient
experienced multiple exposures to asbestos in both occupational and environmental
settings. OBJECTIVES: To collect information on asbestos exposure from all
available sources and to quantify the contribution of each source of exposure as
a percentage of the total risk. METHODS: We retrieved information on jobs done
and asbestos exposure from a work colleague and a database maintained by the
National Institute for Insurance of Occupational Accidents/Diseases,
respectively. Information on environmental exposure was searched through the
scientific literature. The contribution of each source of exposure was quantified
with a method of risk apportionment, taking into account time elapsed since first
and last exposure, intensity and frequency of exposure and carcinogenic potency
of asbestos fiber mix. RESULTS: The subject worked in the maintenance of railway
electrification system. The mechanical compression stress induced on the ballast
during passage of trains released chrysotile (from fragmented stones) and
crocidolite (through abrasive action of crushed gravel on the underbody of
rolling stocks insulated with friable crocidolite). Despite the low cumulative
exposure (about 2 ff*years/cc), 99% of the mesothelioma risk was attributable to
the work done because of the high content of crocidolite of inhaled asbestos.
CONCLUSIONS: The report of an uncommon source of occupational asbestos exposure
and a scientifically based method to allocate mesothelioma risk among multiple
exposure could help to recognize mesothelioma as occupational disease in the
workers employed in maintenance of the railway electrification system under the
Italian National Railways.
PMID- 25134631
TI - [Foot and ankle ability measure: cross-cultural translation and validation of the
Italian version of the ADL module (FAAM-I/ADL)].
AB - BACKGROUND: Valid and reliable outcome measures are fundamental for evaluating
and comparing the effects of rehabilitation. Among the different tools used for
the assessment of musculoskeletal disorders of the lower limb, the Foot and Ankle
Ability Measure (FAAM) has been shown to have good psychometric properties.
However, it has not yet been translated into Italian. The module regarding the
performance of daily living activities (FAAM/ADL), in particular, can be applied
also in an occupational setting. OBJECTIVE: To obtain an Italian version of the
FAAM, and to validate the FAAM-I/ADL. METHODS: The cultural adaptation was
performed according to international guidelines for forward/backward translation.
The activities of daily living (ADL) module of the FAAM-I (FAAM-I/ADL) was
validated with classical test theory methods in a convenience sample of 57
patients. Different parameters were calculated: internal consistency (Cronbach's
alpha and item-to-total correlation); criterion validity, through Pearson's
correlation (r) with the Lower Extremity Functional Scale (LEFS); test-retest
reliability (ICC2,1); Standard Error of Measurement (SEM); and Minimal Detectable
Change (MDC95). RESULTS: The statistical analysis showed good internal
consistency (Cronbach's alpha=.96, item-to-total correlation ranged between .51
and .85), high criterion validity (r=.66, p<0.01) and excellent test-retest
reliability (ICC2, 1=.98, CI95%=.97-.99). The SEM was 2.7 points, with a MDC95 of
7.5 points. CONCLUSIONS: FAAM-I/ADL shows good psychometric properties, together
with speed and ease of administration and scoring. Its use will facilitate the
comparison of Italian data with international studies, ensuring greater
uniformity of assessment.
PMID- 25134627
TI - DNA demethylation and invasive cancer: implications for therapeutics.
AB - One of the hallmarks of cancer is aberrant DNA methylation, which is associated
with abnormal gene expression. Both hypermethylation and silencing of tumour
suppressor genes as well as hypomethylation and activation of prometastatic genes
are characteristic of cancer cells. As DNA methylation is reversible, DNA
methylation inhibitors were tested as anticancer drugs with the idea that such
agents would demethylate and reactivate tumour suppressor genes. Two cytosine
analogues, 5-azacytidine (Vidaza) and 5-aza-2'-deoxycytidine, were approved by
the Food and Drug Administration as antitumour agents in 2004 and 2006
respectively. However, these agents might cause activation of a panel of
prometastatic genes in addition to activating tumour suppressor genes, which
might lead to increased metastasis. This poses the challenge of how to target
tumour suppressor genes and block cancer growth with DNA-demethylating drugs
while avoiding the activation of prometastatic genes and precluding the morbidity
of cancer metastasis. This paper reviews current progress in using DNA
methylation inhibitors in cancer therapy and the potential promise and challenges
ahead.
PMID- 25134632
TI - [The safety data sheets of the paint and coatings sector: analysis of the items
of most interest to health and safety in the workplace].
AB - INTRODUCTION: The interlinked REACH-CLP regulations promote the sharing of
knowledge regarding the risks and hazards of chemicals throughout the supply
chain. The safety data sheet (SDS) is the main instrument to achieve this goal.
OBJECTIVE: to study 100 SDS of paints and coatings sector in order to highlight
major criticisms related to health and safety of workers. MATERIALS AND METHODS:
Using the criteria prescribed by Regulation 453/2010/EC and preparing a suitable
check list, some items of the sections 1 "Identification of the substance/mixture
and of the company", 2 "Hazards identification", 3 "Composition/information on
ingredients", the first part of section 7 "Precautions for safe handling",
sections 8 "Exposure controls/personal protection" and 16 "Other information",
were therefore evaluated for their appropriateness. RESULTS: Seven SDS were
written in a foreign language and were excluded from further analysis. Of the
remaining 93 SDS, only 23% had a proportion of adequate items greater than 80%,
49 % had adequate items between 60 and 80%, and 28% had less than 60% adequate
items. The most critical sections were those relating to workers' safe handling
and exposure controls and protection. CONCLUSION: In conclusion, from the
analysis of SDS we found high percentages of inadequacy, especially in sections 7
and 8, the most relevant for the protection of the health and safety of workers.
PMID- 25134633
TI - [Counterproductive behaviors and moral disengagement of nurses as potential
consequences of stress-related work: validity and reliability of measurement
scales].
AB - BACKGROUND: Several studies, but no one in the nursing, have shown that work
stress can facilitate the adoption of specific behaviors that the literature
identifies as Counterproductive Work Behaviors (CWB). Individuals, however, not
giving up to their moral principles, may transgress social, organizational, moral
and ethical norms, through the adoption of moral disengagement (MD). OBJECTIVES:
The purpose of this study is to validate two specific scales of deviant behaviors
and MD in nursing: the Nursing Counterproductive Work Behaviours Scale (Nursing
CWBS) and Nursing Moral Disengagement Scale (Nursing MDS). METHOD: 460 nurses
participated in the study. After the adaptation of the Counterproductive Work
Behavior Checklist by Spector and Fox to Nursing context (Nursing CWBS) and the
ex novo development of the Nursing MDS, the psychometric properties of the two
scales were tested. Also, the two scales were correlated. RESULTS: Through a
cross-validation approach and based on the results of exploratory factor analysis
(EFA) and confirmatory factor analysis (CFA), we have shown that the scales have
good psychometric properties. Furthermore, the results, attest that the nurse
with high levels of MD implements more CWB in the workplace. CONCLUSIONS: The
Nursing CWBS and Nursing MDS represent a valid starting point for the study of
such phenomena in this specific context where stress among nursing staff is
sometimes of considerable extent, especially in specific contexts of clinical
care.
PMID- 25134634
TI - Work-related musculoskeletal disorders in nursing: current knowledge and ongoing
challenges for occupational health.
AB - Work-related Musculoskeletal Disorders (MSD) represent a major occupational
health concern when considering the relationships between work and disease but
associations between MSD and hospital work, especially in the nursing profession,
aren't yet full understanded.QMSDuestions that still need to be answered include:
Are nurses' work-related musculoskeletal symptoms and injuries dependent on the
wards, the hospital organization and even the national occupational health
policies that they originated from? Is their MSD related with workplaces demands,
equipment, and nurse-patient ratios? Do these factors highlight different nursing
occupational exposure to MSD hazards? What are the individual and psychosocial
contributes to nurses WRMSDs in different nursing contexts? As such, a new
approach which integrates more realistic working conditions, real hospital
equipment, workplace features, and individual information would likely be a
better way forwards in the addressing the current MSD epidemic among hospital
nurses, worldwide......
PMID- 25134636
TI - Cost-effectiveness of health promotion targeting physical activity and healthy
eating in mental health care.
AB - BACKGROUND: There is a higher prevalence of obesity in individuals with mental
disorders compared to the general population. The results of several studies
suggested that weight reduction in this population is possible following psycho
educational and/or behavioural weight management interventions. Evidence of the
effectiveness alone is however inadequate for policy making. The aim of the
current study was to evaluate the cost-effectiveness of a health promotion
intervention targeting physical activity and healthy eating in individuals with
mental disorders. METHODS: A Markov decision-analytic model using a public payer
perspective was applied, projecting the one-year results of a 10-week
intervention over a time horizon of 20 years, assuming a repeated yearly
implementation of the programme. Scenario analysis was applied evaluating the
effects on the results of alternative modelling assumptions. One-way sensitivity
analysis was performed to assess the effects on the results of varying key input
parameters. RESULTS: An incremental cost-effectiveness ratio of 27,096?/quality
adjusted life years (QALY) in men, and 40,139?/QALY in women was found in the
base case. Scenario analysis assuming an increase in health-related quality of
life as a result of the body mass index decrease resulted in much better cost
effectiveness in both men (3,357?/QALY) and women (3,766?/QALY). The uncertainty
associated with the intervention effect had the greatest impact on the model.
CONCLUSIONS: As far as is known to the authors, this is the first health economic
evaluation of a health promotion intervention targeting physical activity and
healthy eating in individuals with mental disorders. Such research is important
as it provides payers and governments with better insights how to spend the
available resources in the most efficient way. Further research examining the
cost-effectiveness of health promotion targeting physical activity and healthy
eating in individuals with mental disorders is required.
PMID- 25134637
TI - Analysis of leucocyte antibodies, cytokines, lysophospholipids and cell
microparticles in blood components implicated in post-transfusion reactions with
dyspnoea.
AB - BACKGROUND AND OBJECTIVES: Post-transfusion reactions with dyspnoea (PTR) are
major causes of morbidity and death after blood transfusion. Transfusion-related
acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO)
are most dangerous, while transfusion-associated dyspnoea (TAD) is a milder
respiratory distress. We investigated blood components for immune and non-immune
factors implicated in PTR. MATERIAL AND METHODS: We analysed 464 blood components
(RBCs, PLTs, L-PLTs, FFP) transfused to 271 patients with PTR. Blood components
were evaluated for 1/antileucocyte antibodies, 2/cytokines: IL-1beta, IL-6, IL-8,
TNF-alpha, sCD40L, 3/lysophosphatidylcholines (LysoPCs), 4/microparticles (MPs)
shed from plateletes (PMPs), erythrocytes (EMPs) and leucocytes (LMPs). RESULTS:
Anti-HLA class I/II antibodies or granulocyte-reactive anti-HLA antibodies were
detected in 18.2% of blood components (RBC and FFP) transfused to TRALI and in
0.5% of FFP transfused to TAD cases. Cytokines and LysoPCs concentrations in
blood components transfused to PTR patients did not exceed those in blood
components transfused to patients with no PTR. Only EMPs percentage in RBCs
transfused to patients with TRALI was significantly higher (P < 0.05) than in
RBCs transfused to patients with no PTR. CONCLUSION: Immune character of PTR was
confirmed mainly in 1/5 TRALI cases. Among non-immune factors, only MPs released
from stored RBCs are suggested as potential mediators of TRALI. Our results
require further observations in a more numerous and better defined group of
patients.
PMID- 25134638
TI - Organisation, practice and experiences of mouth hygiene in stroke unit care: a
mixed-methods study.
AB - AIMS AND OBJECTIVES: To (1) investigate the organisation, provision and practice
of oral care in typical UK stroke units; (2) explore stroke survivors', carers'
and healthcare professionals' experiences and perceptions about the barriers and
facilitators to receiving and undertaking oral care in stroke units. BACKGROUND:
Cerebrovascular disease and oral health are major global health concerns. Little
is known about the provision, challenges and practice of oral care in the stroke
unit setting, and there are currently no evidence-based practice guidelines.
DESIGN: Cross-sectional survey of 11 stroke units across Greater Manchester and
descriptive qualitative study using focus groups and semi-structured interviews.
METHODS: A self-report questionnaire was used to survey 11 stroke units in
Greater Manchester. Data were then collected through two focus groups (n = 10)
with healthcare professionals and five semi-structured interviews with stroke
survivors and carers. Focus group and interview data were recorded, transcribed
verbatim and analysed using framework approach. RESULTS: Eleven stroke units in
Greater Manchester responded to the survey. Stroke survivors and carers
identified a lack of oral care practice and enablement by healthcare
professionals. Healthcare professionals identified a lack of formal training to
conduct oral care for stroke patients, inconsistency in the delivery of oral care
and no set protocols or use of formal oral assessment tools. CONCLUSION: Oral
care post-stroke could be improved by increasing healthcare professionals'
awareness, understanding and knowledge of the potential health benefits of oral
care post-stroke. Further research is required to develop and evaluate the
provision of oral care in stroke care to inform evidence-based education and
practice. RELEVANCE TO CLINICAL PRACTICE: Development of staff training and
education, and evidence-based oral care protocols may potentially benefit patient
care and outcomes and be implemented widely across stroke care.
PMID- 25134639
TI - Sleepiness induced by sleep-debt enhanced amygdala activity for subliminal
signals of fear.
AB - BACKGROUND: Emotional information is frequently processed below the level of
consciousness, where subcortical regions of the brain are thought to play an
important role. In the absence of conscious visual experience, patients with
visual cortex damage discriminate the valence of emotional expression. Even in
healthy individuals, a subliminal mechanism can be utilized to compensate for a
functional decline in visual cognition of various causes such as strong
sleepiness. In this study, sleep deprivation was simulated in healthy individuals
to investigate functional alterations in the subliminal processing of emotional
information caused by reduced conscious visual cognition and attention due to an
increase in subjective sleepiness. Fourteen healthy adult men participated in a
within-subject crossover study consisting of a 5-day session of sleep debt (SD, 4
h sleep) and a 5-day session of sleep control (SC, 8-h sleep). On the last day of
each session, participants performed an emotional face-viewing task that included
backward masking of nonconscious presentations during magnetic resonance
scanning. RESULTS: Finally, data from eleven participants who were unaware of
nonconscious face presentations were analyzed. In fear contrasts, subjective
sleepiness was significantly positively correlated with activity in the amygdala,
ventromedial prefrontal cortex, hippocampus, and insular cortex, and was
significantly negatively correlated with the secondary and tertiary visual areas
and the fusiform face area. In fear-neutral contrasts, subjective sleepiness was
significantly positively correlated with activity of the bilateral amygdala.
Further, changes in subjective sleepiness (the difference between the SC and SD
sessions) were correlated with both changes in amygdala activity and functional
connectivity between the amygdala and superior colliculus in response to
subliminal fearful faces. CONCLUSION: Sleepiness induced functional decline in
the brain areas involved in conscious visual cognition of facial expressions, but
also enhanced subliminal emotional processing via superior colliculus as
represented by activity in the amygdala. These findings suggest that an
evolutionally old and auxiliary subliminal hazard perception system is activated
as a compensatory mechanism when conscious visual cognition is impaired. In
addition, enhancement of subliminal emotional processing might cause involuntary
emotional instability during sleep debt through changes in emotional response to
or emotional evaluation of external stimuli.
PMID- 25134641
TI - Participant Variation by Delivery Site Type in an Evidence-Based Physical
Activity Program.
AB - This study examined participant demographic and physical function characteristics
from EnhanceFitness, an evidence-based physical activity program for older
adults. The sample consisted of 19,964 older adults. Participant data included
self-reported health and demographic variables, and results for three physical
function tests: chair stand, arm curls, and timed up-and-go. Linear regression
models compared physical function test results among eight program site types.
Participants were, on average, 72 years old, predominantly female, and reported
having one chronic condition. Residential site participants' physical function
test results were significantly poorer on chair stand and timed up-and-go
measures at baseline, and timed up-and-go at a four-month follow-up compared with
the reference group (senior centers) after controlling for demographic variables
and site clustering. Evidence-based health-promotion programs offered in
community settings should assess demographic, health, and physical function
characteristics to best serve participants' specific needs, and offer classes
tailored to participant function and ability while maintaining program fidelity.
PMID- 25134642
TI - Route of delivery linked with subsequent childbirth?
PMID- 25134643
TI - Do variations in paraspinal muscle morphology and composition predict low back
pain in men?
AB - This longitudinal study aimed to clarify the longstanding controversy over
whether variations in paraspinal muscle morphology (e.g., size, composition and
asymmetry) are predictors of low back pain (LBP). A sample of 99 Finnish men were
included in this population-based longitudinal study. Data were collected through
a structured interview, physical examination and magnetic resonance imaging
(MRI). Baseline measurements of the lumbar multifidus and erector spinae muscles
were obtained from T2-weighted axial images at L3-L4 and L5-S1, and interview
data were obtained at baseline, 1- and 15-year follow-ups. Few of the paraspinal
muscle parameters investigated were predictors of change in LBP frequency,
intensity or sciatica at 1- and 15-year follow-ups in the population-based
sample, and findings were not consistent across muscles and spinal levels.
However, greater multifidus and erector spinae fatty infiltration at L5-S1 was
associated with a higher risk of having continued, frequent, persistent LBP at 1
year follow-up. None of the relationships observed was confounded by body mass
index or the amount of physical activity at work or leisure. This longitudinal
study provided evidence that variations in paraspinal muscle morphology on MRI
have a limited, if not uncertain, role in the short- and long-term predictions of
LBP in men.
PMID- 25134644
TI - Mycobacterium bovis meningitis in young Nigerian-born male.
AB - In Denmark, tuberculous meningitis is rare. Central nervous system (CNS)
involvement with Mycobacterium bovis is even rarer and has only been seen three
times since 1992. We present a case of M. bovis meningitis in a previously
healthy young Nigerian-born male, who had been exposed to unpasteurized dairy
products in Nigeria but had no known contact with larger mammals. Before the
development of meningitis, the patient had several contacts with the health
system due to fever and non-specific symptoms. Finally, upon hospital admission,
the patient was diagnosed with M. tuberculosis complex meningitis and treated
empirically. After 13 days he was discharged without neurological sequelae.
Later, the culture revealed M. bovis and treatment was adjusted accordingly.
PMID- 25134645
TI - Weekly chlorhexidine douche: does it reduce healthcare-associated bloodstream
infections?
AB - BACKGROUND: Daily chlorhexidine (CHG) bathing has been used as a precaution to
reduce the rate of healthcare-associated bloodstream infections (HA-BSI). The
application frequency of CHG bathing remains unclear, this procedure has been
implemented daily by this time. The aim of this study was to determine the
efficacy of weekly whole-body douche with CHG shower gel on rates of HA-BSI.
METHODS: We conducted a prospective intervention trial in medical, surgical, and
anesthesiology intensive care units (ICUs) in a tertiary teaching hospital from
June 2011 to November 2012. This study included three periods. During the first
period, patients received a daily bed bath by wiping with water and soap. In the
second period patients were given a weekly douche with water and soap; in the
third period patients were given a weekly douche with CHG shower gel. The rates
of HA-BSI were compared between the three periods using Poisson regression
analysis. RESULTS: The central line-associated bloodstream infection rates did
not decline significantly between periods (p = 0.76). The laboratory-confirmed
bloodstream infection (LCBSI) rates in the first, second, and third periods were
7.1, 4, and 1.7, respectively. The LCBSI rates were reduced 43.7% from the first
period to the second period (p = 0.03). In addition, there was a 57.5% reduction
in LCBSI rates between the second and third periods (p < 0.001). Interestingly,
the major decline (76.1%) was determined from the first to the third period (p <
0.002). CONCLUSIONS: Weekly douche with CHG shower gel significantly reduced
LCBSI rates. Further studies are needed to validate the clinical impact of
different intervals of CHG bathing.
PMID- 25134646
TI - Impact of hepcidin antimicrobial peptide on iron overload in tuberculosis
patients.
AB - BACKGROUND: Iron acquisition is essential for the growth of Mycobacterium
tuberculosis. Hepcidin is known as an antimicrobial peptide and a component of
the innate immune response. Hepcidin inhibits M. tuberculosis growth in vitro. In
this study, we decided to identify -582A> G variants of the HAMP promoter in
patients with tuberculosis (TB) and investigate its effect on serum iron,
ferritin, and hepcidin levels. METHODS: The sample population consisted of 105
patients with TB and 104 healthy individuals. The -582A> G polymorphism was
genotyped using a tetra-primers PCR set. Serum levels of hepcidin were determined
using an ELISA kit. Statistical analysis was performed using SPSS software.
RESULTS: The G allele is meaningfully associated with TB disease (95% confidence
interval = 2-4.8, p < 0.000). Significant differences were seen in the levels of
serum iron and hepcidin but not ferritin between the -582A>G polymorphism
genotypes. There was significant reverse correlation between hepcidin and iron (r
= -0.849, p = 0.006). CONCLUSION: A high association was found between serum
hepcidin levels and the HAMP -582A> G variants in patients with TB. These
observations indicate a hypothetical role of this polymorphism in iron
metabolism. Hepcidin could perhaps be an option for the treatment of TB.
PMID- 25134647
TI - High vancomycin minimum inhibitory concentration is associated with poor outcome
in patients with methicillin-susceptible Staphylococcus aureus bacteremia
regardless of treatment.
AB - We retrospectively investigated the impact of high vancomycin minimum inhibitory
concentration (MIC > 2 MUg/ml) on the outcome of 53 patients with bacteremia
caused by methicillin-susceptible Staphylococcus aureus (MSSA). Vancomycin MIC
was determined by broth microdilution according to CLSI methods. The primary
outcome was 30-day all-cause mortality from the date of the first positive blood
culture. The mortality rate was 22.6% (12 of 53 patients). High vancomycin MIC
(odds ratio (OR) = 9.3; 95% confidence interval (95% CI) = 1.31-63.20; p =
0.027), Charlson comorbidity index >= 3 (OR = 10.3; 95% CI = 1.3-102.04; p =
0.03), advanced age (OR = 35.8; 95% CI = 2.3-659.2; p = 0.01), and severe sepsis
(OR = 8.5; 95% CI = 1.2-61.4; p = 0.03) were associated with mortality.
PMID- 25134648
TI - Clinical presentations and outcomes of influenza infection among
hematology/oncology patients from a single cancer center: pandemic and post
pandemic seasons.
AB - BACKGROUND: Influenza can cause severe infection in hematology/oncology patients.
The occurrence of the 2009 pandemic represented an opportunity to study the
impact of influenza on such patients in pandemic and post-pandemic seasons.
METHODS: We retrospectively reviewed medical records of hematology/oncology
patients who had laboratory-confirmed influenza infection during the 2009
pandemic and the first post-pandemic seasons. We assessed influenza-related
outcomes in both seasons with emphasis on the development of pneumonia and
mortality. We also analyzed factors associated with poor outcomes. RESULTS: We
included 350 patients; 207 were diagnosed in the pandemic and 143 in the post
pandemic seasons. Influenza severity was similar in both seasons with no
significant differences in the development of pneumonia or death. Infection with
the pH1N1 virus was associated with the development of pneumonia (24.7% vs 14.9%,
p = 0.029) but did not affect mortality. A multivariate analysis showed that
initiation of antiviral treatment after > 48 h, healthcare acquisition of
influenza, and low albumin were independent risk factors for the development of
pneumonia (p values 0.022, 0.003, and < 0.0001, respectively). A log-rank test
showed increased mortality in patients who received therapy > 48 h after onset of
symptoms (p = 0.001). CONCLUSIONS: In hematology/oncology patients, influenza was
as severe in the post-pandemic as in the pandemic season. Pneumonia developed
more commonly in patients infected with pH1N1 virus. Healthcare acquisition of
infection and low albumin were associated with the development of pneumonia.
Delayed initiation of antiviral treatment was associated with both pneumonia and
mortality.
PMID- 25134649
TI - Usefulness of PCR-RFLP coa gene for clonal classification of methicillin
resistant Staphylococcus aureus isolates in tertiary hospitals.
AB - One hundred and one methicillin-resistant Staphylococcus aureus (MRSA) clinical
isolates were classified into 10 genotypes based on their polymerase chain
reaction-restriction fragment length polymorphism (PCR-RFLP) coa pattern. PCR
RFLP coa patterns correlated with the clonal complex (CC) with the exception of
CC5, which was related to 2 patterns (B and E). The PCR-RFLP coa gene technique
provides a useful preliminary method to monitor variations in MRSA populations.
PMID- 25134651
TI - Misdiagnosed amoebiasis leading to liver abscess.
PMID- 25134650
TI - Cluster of linezolid-resistant Enterococcus faecium ST117 in Norwegian hospitals.
AB - A linezolid-resistant, vancomycin-susceptible Enterococcus faecium strain was
isolated from 3 patients who had not received linezolid. The first patient was
hospitalized in the same hospitals and wards as the 2 following patients. The E.
faecium isolates were resistant to linezolid (minimum inhibitory concentration 8
32 mg/l), ampicillin, and high levels of gentamicin. Resistance to linezolid was
associated with a G2576T mutation in 23S rDNA. The cfr linezolid resistance gene
was not detected. The 3 isolates showed identical DNA fingerprints by pulsed
field gel electrophoresis, belonged to ST117, and harboured virulence genes esp,
hyl, acm, efaAfm, srgA, ecbA, scm, pilA, pilB, and pstD typically associated with
high-risk E. faecium genotypes. The linezolid-resistant E. faecium high-risk
clone caused bacteraemia in the first 2 cancer patients and survived in the
hospital environment for more than a year before appearing in the urethral
catheter of the third patient.
PMID- 25134652
TI - Mycobacterium abscessus: a rare cause of vascular graft infection.
AB - Prosthetic vascular graft infection (PVGI) following vascular reconstructive
surgery is an uncommon but serious complication and is associated with high
morbidity as well as mortality rate. Staphylococcal species are the most common
organisms causing PVGI. Mycobacterium abscessus is a very rare cause of PVGI and
poses a significant diagnostic and management dilemma. To the best of our
knowledge, we report the third documented case of M. abscessus vascular graft
infection that was diagnosed with 18F-fluorodeoxyglucose-positron emission
tomography/computed tomography (FDG-PET/CT) scan and treated successfully.
PMID- 25134653
TI - Acute fulminant hepatitis E virus genotype 3e infection: description of the first
case in Europe.
AB - Hepatitis E virus (HEV) is the most important causative agent of acute hepatitis
in developing countries. The disease is usually characterized by a self-limiting,
benign course. However, when particular conditions coexist (pregnancy, old age,
pre-existing liver disease) it may run an unfavourable course. To date, 4 HEV
genotypes have been described. Historically, in the Western world, HEV infection
was considered a travel-related disease, however in the last 2 decades a great
number of non-travel-related autochthonous cases have been described, more often
related to genotype 3 or 4 and in the context of zoonosis. We report the case of
an elderly Italian man with an acute fulminant HEV infection genotype 3e that
developed in the context of pre-existing liver disease; this is the first case of
an unfavourable outcome associated with subgenotype 3e. The potential
pathogenicity of this subgenotype together with the influence of host-related
risk factors are discussed.
PMID- 25134654
TI - Testing for hepatitis B virus and HIV in patients with chronic hepatitis C:
screening performance and outcome.
AB - BACKGROUND: Patients infected with hepatitis C virus (HCV) and co-infected with
hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV) are at
increased risk for progression of liver disease. The aim of this study was to
assess HBV and HIV screening performance and outcome in HCV patients followed at
a Danish university hospital and affiliated regional outpatient clinics. METHODS:
HBV and HIV serology data were extracted from a quality assurance database for
the assessment of screening performance in patients diagnosed with chronic HCV
infection during the period 1 January 1996 to 31 December 2011. Patients with
incomplete and missing serology data had complementary serology tests performed
to assess the prevalence of HBV and HIV co-infection and HBV immune status.
RESULTS: Among 624 HCV patients, 10 (2%) were co-infected with chronic HBV and 32
(5%) with HIV. Approximately half of the cohort were non-immune to HBV or had an
unknown HBV serology status. Serology results consistent with resolved infection
and HBV vaccination were found in 209 (33%) and 65 (10%) patients, respectively.
During the 16-y observation period, HBV and HIV screening coverage at HCV
diagnosis increased from 23% to 92% and from 38% to 80%, respectively.
CONCLUSION: Despite improvements throughout the study period, HBV and HIV
serology screening remained incomplete. The majority of patients were either HBV
non-immune or had an unknown HBV serology status. These findings thus call for a
more proactive screening approach as well as an improved HBV vaccination strategy
for patients with chronic HCV infection.
PMID- 25134640
TI - DNAH5 is associated with total lung capacity in chronic obstructive pulmonary
disease.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by
expiratory flow limitation, causing air trapping and lung hyperinflation.
Hyperinflation leads to reduced exercise tolerance and poor quality of life in
COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation
particularly in subjects with moderate-to-severe airflow obstruction. The aim of
our study was to identify genetic variants associated with TLC in COPD. METHODS:
We performed genome-wide association studies (GWASs) in white subjects from three
cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify
Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All
subjects were current or ex-smokers with at least moderate airflow obstruction,
defined by a ratio of forced expiratory volume in 1 second to forced vital
capacity (FEV1/FVC) <0.7 and FEV1 < 80% predicted on post-bronchodilator
spirometry. TLC was calculated by using volumetric computed tomography scans at
full inspiration (TLCCT). Genotyping in each cohort was completed, with
statistical imputation of additional markers. To find genetic variants associated
with TLCCT, linear regression models were used, with adjustment for age, sex,
pack-years of smoking, height, and principal components for genetic ancestry.
Results were summarized using fixed-effect meta-analysis. RESULTS: Analysis of a
total of 4,543 COPD subjects identified one genome-wide significant locus on
chromosome 5p15.2 (rs114929486, beta = 0.42L, P = 4.66 * 10-8). CONCLUSIONS: In
COPD, TLCCT was associated with a SNP in dynein, axonemal, heavy chain 5 (DNAH5),
a gene in which genetic variants can cause primary ciliary dyskinesia. DNAH5
could have an effect on hyperinflation in COPD.
PMID- 25134655
TI - A method for lipid droplet isolation from human placenta for further analyses in
clinical trials.
AB - We describe a method to isolate lipids droplets from human placental tissue for
future lipid analyses. We collected placentas at term from healthy women (n=5)
and tested three methods published for lipids droplets isolation in other
tissues. Only one of the methods, when modified, isolated lipids droplets from
placental tissue, whereas all three methods allowed lipids droplets isolation
from rat liver (control tissue) and separation of lipids droplets from blood
contamination of the tissue. The placental lipids droplets layer was
characterized by the presence of adipophilin while no N+ /K+-ATPase as plasma
membrane contamination was detected. Intraplacental triglyceride content showed a
high coefficient of variation (~42%), whereas for cholesterol and phospholipids
this was lower. One method was effective for isolation of placental lipids
droplets. It is necessary to collect a pool of placental tissue pieces for
placental lipids droplets analyses. Freezing in liquid nitrogen is recommended.
PMID- 25134657
TI - Graphitic carbon nitride nanosheets: one-step, high-yield synthesis and
application for Cu2+ detection.
AB - In this article we report on the one-step, rapid, high-yield synthesis of
graphitic carbon nitride (g-C3N4) nanosheets for the first time. The nanosheets
were obtained by pyrolyzing a melamine-KBH4 mixture under Ar. As a fluorosensor
for Cu(2+), the g-C3N4 nanosheets exhibit a detection limit as low as 0.5 nM and
high selectivity in buffer solutions, and this sensor was applied to the analysis
of lake water samples. The electrogenerated chemiluminescence (ECL) behavior of
the g-C3N4 nanosheets using Na2S2O8 as the coreactant was also studied. Results
suggest that the ECL intensity of the g-C3N4 nanosheets was linear over
concentrations of 0-45 nM, with a detection limit of 1.2 nM for Cu(2+).
PMID- 25134659
TI - The omega-3 fatty acid docosahexaenoic acid favorably modulates the inflammatory
pathways and macrophage polarization within aorta of LDLR(-/-) mice.
AB - The omega-3 fatty acid docosahexaenoic acid (DHA) has potent anti-atherogenic
properties but its mechanisms of action at the vascular level remain poorly
explored. Knowing the broad range of molecular targets of omega-3 fatty acids,
microarray analysis was used to open-mindedly evaluate the effects of DHA on
aorta gene expression in LDLR(-/-) mice and better understand its local anti
atherogenic action. Mice were fed an atherogenic diet and received daily oral
gavages with oils rich in oleic acid or DHA. Bioinformatics analysis of
microarray data first identified inflammation and innate immunity as processes
the most affected by DHA supplementation within aorta. More precisely, several
down-regulated genes were associated with the inflammatory functions of
macrophages (e.g., CCL5 and CCR7), cell movement (e.g., ICAM-2, SELP, and PECAM
1), and the major histocompatibility complex (e.g., HLA-DQA1 and HLA-DRB1).
Interestingly, several genes were identified as specific biomarkers of macrophage
polarization, and their changes suggested a preferential orientation toward a M2
reparative phenotype. This observation was supported by the upstream regulator
analysis highlighting the involvement of three main regulators of macrophage
polarization, namely PPARgamma (z-score = 2.367, p = 1.50 * 10(-13)), INFgamma (z
score = -2.797, p = 2.81 * 10(-14)), and NFkappaB (z-score = 2.360, p = 6.32 *
10(-9)). Moreover, immunohistological analysis of aortic root revealed an
increased abundance of Arg1 (+111 %, p = 0.01), a specific biomarker of M2
macrophage. The present study showed for the first time that DHA supplementation
during atherogenesis is associated with protective modulation of inflammation and
innate immunity pathways within aorta putatively through the orientation of
plaque macrophages toward a M2 reparative phenotype.
PMID- 25134658
TI - Content validity of the Comprehensive ICF Core Set for multiple sclerosis from
the perspective of speech and language therapists.
AB - BACKGROUND: The Comprehensive International Classification of Functioning,
Disability and Health (ICF) Core Set for Multiple Sclerosis (MS) is a
comprehensive framework to structure the information obtained in
multidisciplinary clinical settings according to the biopsychosocial perspective
of the International Classification of Functioning, Disability and Health (ICF)
and to guide the treatment and rehabilitation process accordingly. It is now
undergoing validation from the user perspective for which it has been developed
in the first place. AIMS: To validate the content of the Comprehensive ICF Core
Set for MS from the perspective of speech and language therapists (SLTs) involved
in the treatment of persons with MS (PwMS). METHODS & PROCEDURES: Within a three
round e-mail-based Delphi Study 34 SLTs were asked about PwMS' problems,
resources and aspects of the environment treated by SLTs. Responses were linked
to ICF categories. Identified ICF categories were compared with those included in
the Comprehensive ICF Core Set for MS to examine its content validity. OUTCOMES &
RESULTS: Thirty-four SLTs named 524 problems and resources, as well as aspects of
environment. Statements were linked to 129 ICF categories (60 Body-functions
categories, two Body-structures categories, 42 Activities-&-participation
categories, and 25 Environmental-factors categories). SLTs confirmed 46
categories in the Comprehensive ICF Core Set. Twenty-one ICF categories were
identified as not-yet-included categories. CONCLUSIONS & IMPLICATIONS: This study
contributes to the content validity of the Comprehensive ICF Core Set for MS from
the perspective of SLTs. Study participants agreed on a few not-yet-included
categories that should be further discussed for inclusion in a revised version of
the Comprehensive ICF Core Set to strengthen SLTs' perspective in PwMS'
neurorehabilitation.
PMID- 25134660
TI - Treatment of Cushing's disease: a mechanistic update.
AB - Cushing's disease (CD) is characterized by an ACTH-producing anterior
corticotrope pituitary adenoma. If hypothalamus-pituitary-adrenal (HPA) axis
physiology is disrupted, ACTH secretion increases, which in turn stimulates
adrenocortical steroidogenesis and cortisol production. Medical treatment plays
an important role for patients with persistent disease after surgery, for those
in whom surgery is not feasible, or while awaiting effects of radiation. Multiple
drugs, with different mechanisms of action and variable efficacy and tolerability
for controlling the deleterious effects of chronic glucocorticoid excess, are
available. The molecular basis and clinical data for centrally acting drugs,
adrenal steroidogenesis inhibitors, and glucocorticoid receptor antagonists are
reviewed, as are potential novel molecules and future possible targets for CD
treatment. Although progress has been made in the understanding of specific
corticotrope adenoma receptor physiology and recent clinical studies have
detected improved effects with a combined medical therapy approach, there is a
clear need for a more efficacious and better-tolerated medical therapy for
patients with CD. A better understanding of the molecular mechanisms in CD and of
HPA axis physiology should advance the development of new drugs in the future.
PMID- 25134661
TI - Interfacial stability and shape change of anisotropic endoskeleton droplets.
AB - The delivery of suspended active ingredients to a surface is a central function
of numerous commercial cosmetic, drug, and agricultural formulations. Many
products use liquid droplets as a delivery vehicle but, because interfacial
tension keeps droplets spherical, these materials cannot exploit the benefits of
anisotropic shape and shape change offered by solid colloids. In this work,
individual droplet manipulation is used to produce viscoelastic droplets that can
stably retain non-spherical shapes by balancing the Laplace pressure of the
liquid-liquid interface with the elasticity of an internal crystalline network. A
stability criterion is developed for idealized spherocylindrical droplets and
shown to agree with experimental data for varying droplet size and rheology.
Shape change can be induced in the anisotropic droplets by upsetting the balance
of droplet interfacial tension and internal rheology. Using dilution to increase
the interfacial tension shows that external stimuli can trigger collapse and
shape change in these droplets. The droplets wrap around substrates during
collapse, improving contact and adhesion. The model is used to develop design
criteria for production of droplets with tunable response.
PMID- 25134662
TI - Emergency transcatheter arterial embolization for massive hemoptysis due to
pulmonary tuberculosis and tuberculosis sequelae.
AB - To explore the strategy and curative effect of emergency transcatheter arterial
embolization (ETAE) in patients with massive hemoptysis due to pulmonary
tuberculosis and tuberculosis sequelae. A total of 148 patients with massive
hemoptysis due to pulmonary tuberculosis underwent emergency arteriography. After
the bleeding artery was located, patients were given embolotherapy using gelfoam
strips, coils, and polyvinyl alcohol particles. The arteriography manifestations
and therapeutic outcomes in all patients were retrospectively analyzed. ETAE was
performed successfully in 143 patients after location of the bleeding arteries.
The bleeding arteries could not be located in another five patients, and
embolotherapy, therefore, could not be performed. Among these five patients,
three underwent surgical resection and two died of complications of
tuberculosis/fungal ball coinfection. During a 2-year follow-up period, there
were 15 cases of recurrent hemoptysis after initial embolotherapy. Among these,
four cases were resolved by re-embolization, 11 patients still had massive
hemoptysis after re-embolization who underwent surgical resection and resolved
the hemoptysis eventually. Successful hemostasis was achieved by ETAE in 132
patients (89.19%; 132/148). No severe complications occurred after embolotherapy.
ETAE is a safe and effective treatment for massive hemoptysis due to pulmonary
tuberculosis. The key to successful treatment is thorough and complete
embolization of the bleeding arteries. In the event of failure of embolotherapy,
surgical resection should be used to resolve the bleeding.
PMID- 25134664
TI - Low-temperature reduction of brownmillerite CaFeO2.5 in LaAlO3/CaFeO2.5
heterostructures made on SrTiO3.
AB - When LaAlO3/CaFeO2.5 thin-film heterostructures made on SrTiO3 were annealed with
CaH2 at low temperatures below 300 degrees C, the brownmillerite CaFeO2.5 layer
was reduced to CaFeO2 with an infinite-layer structure while both the LaAlO3
capping layer and the SrTiO3 substrate remained intact. The reduction behaviour
strongly depends on the lattice matching of LaAlO3 to CaFeO2.5, suggesting that
oxygen ions migrate through the coherently grown LaAlO3 layer of the
heterostructure predominantly in the out-of-plane direction. The structural
defects near the interface in the relaxed-structure LaAlO3 capping layer prevent
the oxygen ions from migrating.
PMID- 25134663
TI - Knockdown of Akt2 expression by shRNA inhibits proliferation, enhances apoptosis,
and increases chemosensitivity to paclitaxel in human colorectal cancer cells.
AB - Akt2 overexpression correlates with chemoresistance of colorectal cancer (CRC).
However, the cellular functions and precise signals elicited by Akt2 in LSCC have
not been elucidated. Here, we transfected a CRC cell line HCT116 with Akt-2
targeted shRNA in order to establish a cell line with Akt2 knockdown. In vitro
experiments showed that knockdown Akt2 in HCT116 cells was associated with
decrease in cell proliferation as well as enhanced cell apoptosis. Furthermore,
our results demonstrated that Akt2 knockdown correlated with elevated
chemosensitivity of HCT116 cells to paclitaxel. Importantly, we found that
knockdown of AKt2 resulted in downregulation of MDR-1 and MRP-1. Our findings may
lead to a better understanding of the biological effect of Akt2 and may provide
mechanistic insights for developing potential therapeutic strategies targeting
AKt2.
PMID- 25134665
TI - The relationship between promotions committees' identification of problem medical
students and subsequent state medical board actions.
AB - Studies have found unprofessional behavior in medical school was associated with
disciplinary action by state medical boards. For medical schools, promotions
committees are responsible for identifying which students do not demonstrate
academic performance and professional behavior acceptable for promotion and
graduation. The objective of this study was to determine if student
identification by promotions committees during medical school was associated with
disciplinary actions by state medical boards later in practice. We reviewed 20
years of promotions committees' records from a single institution and noted
students identified by promotions committees for performance or behavioral
issues. These were compared with disciplinary action reports from the Federation
of State Medical Boards (FSMB) for graduates. Over the two decades, 2,131
students matriculated and 2,078 of these graduated. The promotions committees
identified 140 students for poor academic performance or behavioral problems
(140/2,078, 6.7 %). Of these, 108 students graduated. FSMB records showed 29 of
the 2,078 graduates had sanctions by state boards (29/2,078, 1.4 %). Only four
students that had actions by state medical boards were among the 108 graduated
students identified by medical school promotions committees (4/108, 3.7 %). Of
the students not identified by promotions committees, 25 eventually had
disciplinary actions (25/1,970, 1.3 %). The odds of having state medical board
action if identified by promotions committees was 3.0 (CI 1.02-8.8, p < 0.05). In
conclusion, identification of students by medical school promotions committees
was later associated with state medical board actions. However, most graduates
with state medical board actions were not identified by medical school promotions
committees.
PMID- 25134666
TI - Cost in medical education: one hundred and twenty years ago.
AB - The first full paper that is dedicated to cost in medical education appears in
the BMJ in 1893. This paper "The cost of a medical education" outlines the likely
costs associated with undergraduate education at the end of the nineteenth
century, and offers guidance to the student on how to make financial planning.
Many lessons can be gleaned from the paper about the cost and other aspects of
nineteenth century medical education. Cost is viewed almost exclusively from the
domain of the male gender. Cost is viewed not just from the perspective of a
young man but of a young gentleman. There is a strong implication that medicine
is a club and that you have to have money to join the club and then to take part
in the club's activities. Cost affects choice of medical school and selection
into schools. The paper places great emphasis on the importance of passing exams
at their first sitting and progressing through each year in a timely manner
mainly to save costs. The subject of cost is viewed from the perspective of the
payer-at this time students and their families. The paper encourages the reader
to reflect on what has and has not changed in this field since 1893. Modern
medical education is still expensive; its expense deters students; and we have
only started to think about how to control costs or how to ensure value. Too much
of the cost of medical education continues to burden students and their families.
PMID- 25134667
TI - Estimating a DIF decomposition model using a random-weights linear logistic test
model approach.
AB - A differential item functioning (DIF) decomposition model separates a testlet
item DIF into two sources: item-specific differential functioning and testlet
specific differential functioning. This article provides an alternative model
building framework and estimation approach for a DIF decomposition model that was
proposed by Beretvas and Walker (2012). Although their model is formulated under
multilevel modeling with the restricted pseudolikelihood estimation method, our
approach illustrates DIF decomposition modeling that is directly built upon the
random-weights linear logistic test model framework with the marginal maximum
likelihood estimation method. In addition to demonstrating our approach's
performance, we provide detailed information on how to implement this new DIF
decomposition model using an item response theory software program; using DIF
decomposition may be challenging for practitioners, yet practical information on
how to implement it has previously been unavailable in the measurement
literature.
PMID- 25134668
TI - Chinese English Learners' Strategic Competence.
AB - The present study aims to investigate Chinese English learners' ability to use
communication strategies (CSs). The subjects are put in a relatively real English
referential communication setting and the analyses of the research data show that
Chinese English learners, when encountering problems in foreign language (FL)
communication, are characterized by the frequent use of substitution,
approximation, circumlocution, literal translation, exemplification, word
coinage, repetition, and the infrequent use of cultural-knowledge and
paralinguistic CSs. The rare use of paralinguistic strategies is found to be
typical of Chinese English learners. The high frequency of literal translation,
one first language (L1)-based strategy in our study sample, suggests that FL
learners' use of L1-based CSs may depend more upon the developmental stage of
their target language than the typology distance between L1 and the target
language. The frequency of repetition reveals one fact that the Chinese English
learners lack variety and flexibility in their use of CSs. Based on these
findings, it was indicated that learners' use of CSs is influenced by a variety
of factors, among which the development stage of their interlanguage and their
cultural background are identified as two important factors. Some implications
are finally suggested for the English foreign language teaching practice in
China.
PMID- 25134669
TI - 18F-FDG PET of the hands with a dedicated high-resolution PEM system (arthro
PET): correlation with PET/CT, radiography and clinical parameters.
AB - PURPOSE: The aim of this study was to prospectively determine the feasibility and
compare the novel use of a positron emission mammography (PEM) scanner with
standard PET/CT for evaluating hand osteoarthritis (OA) with (18)F-FDG. METHODS:
Institutional review board approval and written informed consent were obtained
for this HIPAA-compliant prospective study in which 14 adults referred for
oncological (18)F-FDG PET/CT underwent dedicated hand PET/CT followed by arthro
PET using the PEM device. Hand radiographs were obtained and scored for the
presence and severity of OA. Summed qualitative and quantitative joint glycolytic
scores for each modality were compared with the findings on plain radiography and
clinical features. RESULTS: Eight patients with clinical and/or radiographic
evidence of OA comprised the OA group (mean age 73 +/- 7.7 years). Six patients
served as the control group (53.7 +/- 9.3 years). Arthro-PET quantitative and
qualitative joint glycolytic scores were highly correlated with PET/CT findings
in the OA patients (r = 0.86. p = 0.007; r = 0.94, p = 0.001). Qualitative arthro
PET and PET/CT joint scores were significantly higher in the OA patients than in
controls (38.7 +/- 6.6 vs. 32.2 +/- 0.4, p = 0.02; 37.5 +/- 5.4 vs. 32.2 +/- 0.4,
p = 0.03, respectively). Quantitative arthro-PET and PET/CT maximum SUV-lean
joint scores were higher in the OA patients, although they did not reach
statistical significance (20.8 +/- 4.2 vs. 18 +/- 1.8, p = 0.13; 22.8 +/- 5.38
vs. 20.1 +/- 1.54, p = 0.21). By definition, OA patients had higher radiographic
joint scores than controls (30.9 +/- 31.3 vs. 0, p = 0.03). CONCLUSION: Hand
imaging using a small field of view PEM system (arthro-PET) with FDG is feasible,
performing comparably to PET/CT in assessing metabolic joint activity. Arthro-PET
and PET/CT showed higher joint FDG uptake in OA. Further exploration of arthro
PET in arthritis management is warranted.
PMID- 25134670
TI - (68)Ga-DOTATOC PET/CT provides accurate tumour extent in patients with
extraadrenal paraganglioma compared to (123)I-MIBG SPECT/CT.
AB - PURPOSE: The aim of this study was to compare the accuracy of (123)I-MIBG
SPECT/CT with that of (68)Ga-DOTATOC PET/CT for staging extraadrenal
paragangliomas (PGL) using both functional and anatomical images (i.e. combined
cross-sectional imaging) as the reference standards. METHODS: The study included
three men and seven women (age range 26 to 73 years) with anatomical and/or
histologically proven disease. Three patients had either metastatic head and neck
PGL (HNPGL) or multifocal extraadrenal PGL, and seven patients had nonmetastatic
extraadrenal disease. Comparative evaluation included morphological imaging with
CT, functional imaging with (68)Ga-DOTATOC PET, and (123)I-MIBG imaging. The
imaging results were analysed on a per-patient and on a per-lesion basis.
RESULTS: On a per-patient basis, the detection rate of (68)Ga-DOTATOC PET was 100
%, whereas that of planar (123)I-MIBG imaging was 10.0 % and with SPECT/CT 20.0 %
for both nonmetastatic and metastatic/multifocal extraadrenal PGL. On a per
lesion basis, the overall sensitivity of (68)Ga-DOTATOC PET was 100 % (McNemar p
< 0.5), that of planar (123)I-MIBG imaging was 3.4 % (McNemar p < 0.001) and that
of SPECT/CT was 6.9 % (McNemar p < 0.001). Both (68)Ga-DOTATOC PET and anatomical
imaging identified 27 lesions. Planar (123)I-MIBG imaging identified only one
lesion, and SPECT/CT two lesions. Two additional lesions were detected by (68)Ga
DOTATOC PET but not by either (123)I-MIBG or CT imaging. CONCLUSION: Our analysis
in this patient cohort indicated that (68)Ga-DOTATOC PET/CT is superior to (123)I
MIBG SPECT/CT, particularly in head and neck and bone lesions, and provides
valuable information for staging extraadrenal PGL, particularly in patients with
surgically inoperable tumours or multifocal/malignant disease.
PMID- 25134673
TI - Quantitative proteomics reveals the kinetics of trypsin-catalyzed protein
digestion.
AB - Trypsin is the popular protease to digest proteins into peptides in shotgun
proteomics, but few studies have attempted to systematically investigate the
kinetics of trypsin-catalyzed protein digestion in proteome samples. In this
study, we applied quantitative proteomics via triplex stable isotope dimethyl
labeling to investigate the kinetics of trypsin-catalyzed cleavage. It was found
that trypsin cleaves the C-terminal to lysine (K) and arginine (R) residues with
higher rates for R. And the cleavage sites surrounded by neutral residues could
be quickly cut, while those with neighboring charged residues (D/E/K/R) or
proline residue (P) could be slowly cut. In a proteome sample, a huge number of
proteins with different physical chemical properties coexists. If any type of
protein could be preferably digested, then limited digestion could be applied to
reduce the sample complexity. However, we found that protein abundance and other
physicochemical properties, such as molecular weight (Mw), grand average of
hydropathicity (GRAVY), aliphatic index, and isoelectric point (pI) have no
notable correlation with digestion priority of proteins.
PMID- 25134674
TI - Emerging concepts and strategies in analytical glow discharges.
PMID- 25134672
TI - Belinostat: first global approval.
AB - Belinostat [Beleodaq((r)) (US)], a small-molecule hydroxamate-type inhibitor of
class I, II and IV histone deacetylase (HDAC) enzymes, has been developed by
TopoTarget and Spectrum Pharmaceuticals for the treatment of relapsed or
refractory peripheral T-cell lymphoma (PTCL). Belinostat has received its first
global approval as monotherapy for this indication in the US, under the Food and
Drug Administration's accelerated approval program. This article summarizes the
milestones in the development of belinostat leading to this first approval for
the treatment of PTCL.
PMID- 25134671
TI - Chronic renal insufficiency in heart transplant recipients: risk factors and
management options.
AB - Renal dysfunction after heart transplantation is a frequently observed
complication, in some cases resulting in significant limitation of quality of
life and reduced survival. Since the pathophysiology of renal failure (RF) is
multifactorial, the current etiologic paradigm for chronic kidney disease after
heart transplantation relies on the concept of calcineurin inhibitor (CNI)
related nephrotoxicity acting on a predisposed recipient. Until recently, the
management of RF has been restricted to the minimization of CNI dosage and
general avoidance of classic nephrotoxic risk factors, with somewhat limited
success. The recent introduction of proliferation signal inhibitors (PSIs)
(sirolimus and everolimus), a new class of immunosuppressive drugs lacking
intrinsic nephrotoxicity, has provided a completely new alternative in this
clinical setting. As clinical experience with these new drugs increases, new
renal-sparing strategies are becoming available. PSIs can be used in combination
with reduced doses of CNIs and even in complete CNI-free protocols. Different
strategies have been devised, including de novo use to avoid acute renal toxicity
in high-risk patients immediately after transplantation, or more delayed
introduction in those patients developing chronic RF after prolonged CNI
exposure. In this review, the main information on the clinical relevance and
pathophysiology of RF after heart transplantation, as well as the currently
available experience with renal-sparing immunosuppressive regimens, particularly
focused on the use of PSIs, is reviewed and summarized, including the key
practical points for their appropriate clinical usage.
PMID- 25134675
TI - Can mercury in fish be reduced by water level management? Evaluating the effects
of water level fluctuation on mercury accumulation in yellow perch (Perca
flavescens).
AB - Mercury (Hg) contamination of fisheries is a major concern for resource managers
of many temperate lakes. Anthropogenic Hg contamination is largely derived from
atmospheric deposition within a lake's watershed, but its incorporation into the
food web is facilitated by bacterial activity in sediments. Temporal variation in
Hg content of fish (young-of-year yellow perch) in the regulated lakes of the
Rainy-Namakan complex (on the border of the United States and Canada) has been
linked to water level (WL) fluctuations, presumably through variation in sediment
inundation. As a result, Hg contamination of fish has been linked to
international regulations of WL fluctuation. Here we assess the relationship
between WL fluctuations and fish Hg content using a 10-year dataset covering six
lakes. Within-year WL rise did not appear in strongly supported models of fish
Hg, but year-to-year variation in maximum water levels (?maxWL) was positively
associated with fish Hg content. This WL effect varied in magnitude among lakes:
In Crane Lake, a 1 m increase in ?maxWL from the previous year was associated
with a 108 ng increase in fish Hg content (per gram wet weight), while the same
WL change in Kabetogama was associated with only a 5 ng increase in fish Hg
content. In half the lakes sampled here, effect sizes could not be distinguished
from zero. Given the persistent and wide-ranging extent of Hg contamination and
the large number of regulated waterways, future research is needed to identify
the conditions in which WL fluctuations influence fish Hg content.
PMID- 25134676
TI - Cytochrome P4501A1 expression in blubber biopsies of endangered false killer
whales (Pseudorca crassidens) and nine other odontocete species from Hawai'i.
AB - Odontocetes (toothed whales) are considered sentinel species in the marine
environment because of their high trophic position, long life spans, and blubber
that accumulates lipophilic contaminants. Cytochrome P4501A1 (CYP1A1) is a
biomarker of exposure and molecular effects of certain persistent organic
pollutants. Immunohistochemistry was used to visualize CYP1A1 expression in
blubber biopsies collected by non-lethal sampling methods from 10 species of free
ranging Hawaiian odontocetes: short-finned pilot whale, melon-headed whale, pygmy
killer whale, common bottlenose dolphin, rough-toothed dolphin, pantropical
spotted dolphin, Blainville's beaked whale, Cuvier's beaked whale, sperm whale,
and endangered main Hawaiian Islands insular false killer whale. Significantly
higher levels of CYP1A1 were observed in false killer whales and rough-toothed
dolphins compared to melon-headed whales, and in general, trophic position
appears to influence CYP1A1 expression patterns in particular species groups. No
significant differences in CYP1A1 were found based on age class or sex across all
samples. However, within male false killer whales, juveniles expressed
significantly higher levels of CYP1A1 when compared to adults. Total
polychlorinated biphenyl (?PCBs) concentrations in 84% of false killer whales
exceeded proposed threshold levels for health effects, and ?PCBs correlated with
CYP1A1 expression. There was no significant relationship between PCB toxic
equivalent quotient and CYP1A1 expression, suggesting that this response may be
influenced by agonists other than the dioxin-like PCBs measured in this study. No
significant differences were found for CYP1A1 expression among social clusters of
false killer whales. This work provides a foundation for future health monitoring
of the endangered stock of false killer whales and other Hawaiian odontocetes.
PMID- 25134677
TI - Microcalorimetric study of the effects of long-term fertilization on soil
microbial activity in a wheat field on the Loess Plateau.
AB - The effects of the long-term inorganic (nitrogen, N; phosphate, P) and organic
(manure, M; straw, S) fertilizers/managemenet individually and in combinations
(N, NP, SNP, M, and MNP) on soil microbial activity were investigated in a wheat
field on the Loess Plateau, China. Microcalorimetry was used to determine
microbial activity under different treatments. Nearly 30 years of consecutive
fertilization has altered the culturable population of soil bacteria and fungi,
the highest ones were detected in the treatments of manure and MNP, followed by
the NP and SNP treatments. The microbial growth rate constant (MU/h(-1)) was
significantly greater in the MNP treatment than all the other treatments. The
total heat exchange values (Q/J) were the highest in the MNP and NP treatments,
which were significantly different from the N and M treatments. The peak height
(P(t)/MUW) were significantly higher in MNP and NP treatments than in the
remaining treatments. The peak time values (t(p)/h) among the MNP, NP, SNP and M,
N and CK treatments were significantly different. In general, comparing with
control, soil microbial activity was much higher in MNP, NP and SNP treatments,
all including the phosphate fertilizer. Our results showed that the application
of inorganic fertilizer and organic manure have positive effects on multiple soil
chemical parameters, soil microorganism abundance and activity, and hence crop
yield.
PMID- 25134678
TI - Effect of triclosan on reproduction, DNA damage and heat shock protein gene
expression of the earthworm Eisenia fetida.
AB - Triclosan (TCS) is released into the terrestrial environment via the application
of sewage sludge and reclaimed water to agricultural land. More attention has
been paid to its effect on non-target soil organisms. In the present study,
chronic toxic effects of TCS on earthworms at a wide range of concentrations were
investigated. The reproduction, DNA damage, and expression levels of heat shock
protein (Hsp70) gene of earthworms were studied as toxicity endpoints. The
results showed that the reproduction of earthworms were significantly reduced (p
< 0.05) after exposure to the concentrations ranges from 50 to 300 mg kg(-1),
with a half-maximal effective concentration (EC50) of 142.11 mg kg(-1). DNA
damage, detected by the comet assay, was observed and there was a clear
significant (R(2) = 0.941) relationship between TCS concentrations and DNA
damage, with the EC50 value of 8.85 mg kg(-1). The expression levels of Hsp70
gene of earthworms were found to be up-regulated under the experimental
conditions. The expression level of hsp70 gene increased, up to about 2.28 folds
that in the control at 50 mg kg(-1). The EC50 value based on the Hsp70 biomarker
was 1.79 mg kg(-1). Thus, among the three toxicity endpoints, the Hsp70 gene was
more sensitive to TCS in soil.
PMID- 25134679
TI - Long-term effects of fertilizer on soil enzymatic activity of wheat field soil in
Loess Plateau, China.
AB - The effects of long-term (29 years) fertilization on local agro-ecosystems in the
Loess Plateau of northwest China, containing a single or combinations of
inorganic (Nitrogen, N; Phosphate, P) and organic (Mature, M Straw, S)
fertilizer, including N, NP, SNP, M, MNP, and a control. The soil enzymes,
including dehydrogenase, urease, alkaline phosphatase, invertase and glomalin,
were investigated in three physiological stages (Jointing, Dough, and Maturity)
of wheat growth at three depths of the soil profile (0-15, 16-30, 31-45 cm). We
found that the application of farmyard manure and straw produced the highest
values of soil enzymatic activity, especially a balanced applied treatment of
MNP. Enzymatic activity was lowest in the control. Values were generally highest
at dough, followed by the jointing and maturity stages, and declined with soil
profile depth. The activities of the enzymes investigated here are significantly
correlated with each other and are correlated with soil nutrients, in particular
with soil organic carbon. Our results suggest that a balanced application of
fertilizer nutrients and organic manure (especially those containing P) has
positive effects on multiple soil chemical parameters, which in turn enhances
enzyme activity. We emphasize the role of organic manure in maintaining soil
organic matter and promoting biological activity, as its application can result
in a substantial increase in agricultural production and can be sustainable for
many years.
PMID- 25134680
TI - Aging of the nitric oxide system: are we as old as our NO?
AB - BACKGROUND: Impaired generation and signaling of nitric oxide (NO) contribute
substantially to cardiovascular (CV) risk (CVR) associated with hypertension,
hyperlipidemia, and diabetes mellitus. In our rapidly aging society, advanced age
is, in itself, a consistent and independent CVR factor. Many processes involved
in aging are modulated by NO. We therefore postulated that aging might be
independently associated with impaired NO signaling. METHODS AND RESULTS: In a
prospective cohort study of 204 subjects (mean age 63+/-6 at study entry), we
evaluated the effects of 4 years of aging on parameters of NO generation and
effect, including platelet aggregability and responsiveness to NO, and plasma
concentrations of the NO synthase inhibitor, asymmetric dimethylarginine (ADMA).
Clinical history, lipid profile, high-sensitivity C-reactive protein, routine
biochemistry, and 25-hydroxyvitamin D levels were obtained at study entry and
after 4 years of follow-up. Aging was associated with marked deterioration of
responsiveness of platelets to NO (P<0.0001) and increases in plasma ADMA
concentrations (P<0.0001). There was a significant correlation between changes in
these parameters over time (r=0.2; P=0.013). On multivariable analyses, the
independent correlates of deterioration of responsiveness of platelets to NO were
female gender (beta=0.17; P=0.034) and low vitamin D concentrations (beta=0.16;
P=0.04), whereas increases in ADMA were associated with presence of diabetes
(beta=0.16; P=0.03) and impaired renal function (beta=0.2; P=0.004). CONCLUSIONS:
Aging is associated with marked impairment of determinants of NO generation and
effect, to an extent which is commensurate with adverse impact on CV outcomes.
This deterioration represents a potential target for therapeutic interventions.
PMID- 25134683
TI - Prefronto-subcortical imbalance characterizes poor decision-making: neurochemical
and neural functional evidences in rats.
AB - A major challenge of decision-making research in recent years has been to develop
models of poor decision-making to identify its neural bases. Toward this goal, we
developed a Rat Gambling Task that discerns good and poor decision-makers in a
complex and conflicting situation such as the human Iowa Gambling Task. Nothing
is known about the role of the monoaminergic modulatory systems in shaping these
phenotypes. Moreover, functional and temporal contributions of brain areas during
poor compared to good decision-making remains elusive. Good and poor decision
makers were identified in the Rat Gambling Task. We investigated neurobiological
correlates of decision-making capacities in (1) dopamine and serotonin turnovers
using post-mortem tissue measurements, (2) the neural circuits differentially
recruited during decision-making within the prefronto-subcortical network using
cellular Fos immunodetection. Imbalance in monoamine metabolism was revealed in
poor decision-makers, i.e. a higher infralimbic vs. lower amygdala serotonergic
metabolism. Moreover, good decision-making recruited a wide prefronto-subcortical
network but once good choices had been made, a disengagement of key prefrontal
areas (insular and infralimbic cortices notably) and the amygdala was observed.
By contrast, poor decision-making was associated with a strikingly low
recruitment of the prefronto-subcortical network, together with sustained
amygdala activity. Our results identify two complementary neurobiological
substrates characterizing poor decision-makers: imbalanced monoaminergic systems
at rest, congruent with their previously identified complex behavioral phenotype,
and an aberrant low recruitment of key brain areas for executive functions and
affective valence during the process of decision-making. These biomarkers could
sustain vulnerability to developing poor decision-making related disorders.
PMID- 25134681
TI - Red cell distribution width is associated with incident myocardial infarction in
a general population: the Tromso Study.
AB - BACKGROUND: Red cell distribution width (RDW), a measure of the variability in
size of circulating erythrocytes, is associated with mortality and adverse
outcome in selected populations with cardiovascular disease. It is scarcely known
whether RDW is associated with incident myocardial infarction (MI). We aimed to
investigate whether RDW was associated with risk of first-ever MI in a large
cohort study with participants recruited from a general population. METHODS AND
RESULTS: Baseline characteristics, including RDW, were collected for 25 612
participants in the Tromso Study in 1994-1995. Incident MI during follow-up was
registered from inclusion through December 31, 2010. Cox regression models were
used to calculate hazard ratios with 95% confidence intervals for MI, adjusted
for age, sex, body mass index, smoking, hemoglobin, white blood cells, platelets,
and other traditional cardiovascular risk factors. A total of 1779 participants
experienced a first-ever MI during a median follow-up time of 15.8 years. There
was a linear association between RDW and risk of MI, for which a 1% increment in
RDW was associated with a 13% increased risk (hazard ratio 1.13; 95% CI, 1.07 to
1.19). Participants with RDW above the 95th percentile had 71% higher risk of MI
compared with those with RDW in the lowest quintile (hazard ratio 1.71; 95% CI,
1.34 to 2.20). All effect estimates were essentially similar after exclusion of
participants with anemia (n=1297) from the analyses. CONCLUSION: RDW is
associated with incident MI in a general population independent of anemia and
cardiovascular risk factors.
PMID- 25134684
TI - TMS stimulation over the inferior parietal cortex disrupts prospective sense of
agency.
AB - Sense of agency refers to the feeling of controlling an external event through
one's own action. On one influential view, sense of agency is inferred after an
action, by "retrospectively" comparing actual effects of actions against their
intended effects. However, it has been recently shown that earlier processes,
linked to action selection, may also contribute to sense of agency, in advance of
the action itself, and independently of action effects. The inferior parietal
cortex (IPC) may underpin this "prospective" contribution to agency, by
monitoring signals relating to fluency of action selection in dorsolateral
prefrontal cortex (DLPFC). Here, we combined transcranial stimulation (TMS) with
subliminal priming of action selection to investigate the causal role of these
regions in the prospective coding of agency. In a first experiment, we showed
that TMS over left IPC at the time of action selection disrupts perceived control
over subsequent effects of action. In a second experiment, we exploited the
temporal specificity of single-pulse TMS to pinpoint the exact timing of IPC
contribution to sense of agency. We replicated the reduction in perceived control
at the point of action selection, while observing no effect of TMS-induced
disruption of IPC at the time of action outcomes.
PMID- 25134682
TI - Contralateral cerebello-thalamo-cortical pathways with prominent involvement of
associative areas in humans in vivo.
AB - In addition to motor functions, it has become clear that in humans the cerebellum
plays a significant role in cognition too, through connections with associative
areas in the cerebral cortex. Classical anatomy indicates that neo-cerebellar
regions are connected with the contralateral cerebral cortex through the dentate
nucleus, superior cerebellar peduncle, red nucleus and ventrolateral anterior
nucleus of the thalamus. The anatomical existence of these connections has been
demonstrated using virus retrograde transport techniques in monkeys and rats ex
vivo. In this study, using advanced diffusion MRI tractography we show that it is
possible to calculate streamlines to reconstruct the pathway connecting the
cerebellar cortex with contralateral cerebral cortex in humans in vivo.
Corresponding areas of the cerebellar and cerebral cortex encompassed similar
proportion (about 80%) of the tract, suggesting that the majority of streamlines
passing through the superior cerebellar peduncle connect the cerebellar
hemispheres through the ventrolateral thalamus with contralateral associative
areas. This result demonstrates that this kind of tractography is a useful tool
to map connections between the cerebellum and the cerebral cortex and moreover
could be used to support specific theories about the abnormal communication along
these pathways in cognitive dysfunctions in pathologies ranging from dyslexia to
autism.
PMID- 25134685
TI - Chromophore composition of the phycobiliprotein Cr-PC577 from the cryptophyte
Hemiselmis pacifica.
AB - The cryptophyte phycocyanin Cr-PC577 from Hemiselmis pacifica is a close relative
of Cr-PC612 found in Hemiselmis virescens and Hemiselmis tepida. The two
biliproteins differ in that Cr-PC577 lacks the major peak at around 612 nm in the
absorption spectrum. Cr-PC577 was thus purified and characterized with respect to
its bilin chromophore composition. Like other cryptophyte phycobiliproteins, Cr
PC577 is an (alphabeta)(alpha'beta) heterodimer with phycocyanobilin (PCB) bound
to the alpha-subunits. While one chromophore of the beta-subunit is also PCB,
mass spectrometry identified an additional chromophore with a mass of 585 Da at
position beta-Cys-158. This mass can be attributed to either a dihydrobiliverdin
(DHBV), mesobiliverdin (MBV), or bilin584 chromophore. The doubly linked bilin at
position beta-Cys-50 and beta-Cys-61 could not be identified unequivocally but
shares spectral features with DHBV. We found that Cr-PC577 possesses a novel
chromophore composition with at least two different chromophores bound to the
beta-subunit. Overall, our data contribute to a better understanding of
cryptophyte phycobiliproteins and furthermore raise the question on the
biosynthetic pathway of cryptophyte chromophores.
PMID- 25134686
TI - Dolutegravir, the Second-Generation of Integrase Strand Transfer Inhibitors
(INSTIs) for the Treatment of HIV.
AB - The integrase strand transfer inhibitors (INSTIs) are the newest antiretroviral
class in the HIV treatment armamentarium. Dolutegravir (DTG) is the only second
generation INSTI with FDA approval (2013). It has potential advantages in
comparison to first-generation INSTI's, including unboosted daily dosing, limited
cross resistance with raltegravir and elvitegravir, and a high barrier to
resistance. Clinical trials have evaluated DTG as a 50-mg daily dose in both
treatment-naive and treatment-experienced, INSTI-naive participants. In those
treatment-naive participants with baseline viral load <100,000 copies/mL, DTG
combined with abacavir and lamivudine was non-inferior and superior to fixed-dose
combination emtricitabine/tenofovir/efavirenz. DTG was also superior to the
protease inhibitor regimen darunavir/ritonavir in treatment-naive participants
regardless of baseline viral load. Among treatment-experienced patients naive to
INSTI, DTG (50 mg daily) demonstrated both non-inferiority and superiority when
compared to the first-generation INSTI raltegravir (400 mg twice daily)
regardless of the background regimen. No phenotypically significant DTG
resistance has been demonstrated in INSTI-naive participant trials. The VIKING
trials evaluated DTG's ability to treat persons with HIV with prior INSTI
exposure. VIKING demonstrated twice-daily DTG was more efficacious than daily
dosing when treating participants receiving and failing first-generation INSTI
regimens. DTG maintained potency against single mutations from any of the three
major INSTI pathways (Y143, H155, Q148); however, the Q148 mutation with two or
more additional mutations significantly reduced its potency. The long-acting
formulation of DTG, GSK1265744LA, is the next innovation in this second
generation INSTI class, holding promise for the future of HIV prevention and
treatment.
PMID- 25134688
TI - Factors influencing knowledge and practice of hygiene in Water, Sanitation and
Hygiene (WASH) programme areas of Bangladesh Rural Advancement Committee.
AB - INTRODUCTION: Improved hygiene is one of the most effective means of reducing
disease occurrence. However, a complete understanding of the factors that
contribute to such improvement are not clear. This study explored factors that
facilitate and/or impede hygiene behavior in water, sanitation and hygiene (WASH)
intervention areas using qualitative research techniques. METHODS: The Bangladesh
Rural Advancement Committee (BRAC) has been providing WASH intervention to 150
rural upazilas (sub-districts) since 2006. For qualitative data collection, in
depth interviews were conducted with 144 purposively selected women from six
upazilas across Bangladesh. A woman in the household was considered as a case and
interviewed regarding various aspects of sanitation and hygiene, using a
checklist. Some practices, such as cleanliness of latrines, and availability of
soap, water, slippers in their designated place were physically verified.
RESULTS: The respondents' hygiene behavior was mainly facilitated by improved
knowledge and awareness of health and environment-related issues. Latrine
ownership increased through financial assistance, resulting in improved privacy,
social prestige, and a heightened sense of responsibility towards maintaining a
healthy life. However, lack of interest in attending cluster meetings,
traditional knowledge, poverty, and lack of will were some of the factors
impeding knowledge and hygiene practice. In addition, attitude played a
definitive role, with some respondents not practicing hygiene in spite of having
the financial ability to do so. They expected full financial support for creating
sanitation and hygiene facilities in their household despite BRAC's policy of
providing such support only to the 'ultra-poor'. CONCLUSIONS: The identified
impeding factors often act as barriers to transformation of hygiene-related
knowledge into practice and practice into habit. More motivational cluster
meetings with large-scale participation and periodic home visits by the programme
organizers are imperative as they markedly improve hygiene behavior.
PMID- 25134689
TI - Abstracts of the 50th EASD Annual Meeting, September 15-19, 2014, Vienna,
Austria.
PMID- 25134687
TI - Hypoxia-Inducible Factor (HIF) as a Pharmacological Target for Prevention and
Treatment of Infectious Diseases.
AB - In the present era of ever-increasing antibiotic resistance and increasingly
complex and immunosuppressed patient populations, physicians and scientists are
seeking novel approaches to battle difficult infectious disease conditions.
Development of a serious infection implies a failure of innate immune
capabilities in the patient, and one may consider whether pharmacological
strategies exist to correct and enhance innate immune cell function. Hypoxia
inducible factor-1 (HIF-1), the central regulator of the cellular response to
hypoxic stress, has recently been recognized to control the activation state and
key microbicidal functions of immune cells. HIF-1 boosting drugs are in clinical
development for anemia and other indications, and could be repositioned as
infectious disease therapeutics. With equal attention to opportunities and
complexities, we review our current understanding of HIF-1 regulation of
microbial host-pathogen interactions with an eye toward future drug development.
PMID- 25134691
TI - Statistics: general linear models (a flexible approach).
AB - This article moves on to discuss a type of statistical testing different from
those we have discussed previously, namely a General Linear Model. This system
incorporates a number of other statistical models and is a powerful tool used
widely in modern statistics.
PMID- 25134690
TI - Protocols utilizing constant pH molecular dynamics to compute pH-dependent
binding free energies.
AB - In protein-ligand binding, the electrostatic environments of the two binding
partners may vary significantly in bound and unbound states, which may lead to
protonation changes upon binding. In cases where ligand binding results in a net
uptake or release of protons, the free energy of binding is pH-dependent.
Nevertheless, conventional free energy calculations and molecular docking
protocols typically do not rigorously account for changes in protonation that may
occur upon ligand binding. To address these shortcomings, we present a simple
methodology based on Wyman's binding polynomial formalism to account for the pH
dependence of binding free energies and demonstrate its use on cucurbit[7]uril
(CB[7]) host-guest systems. Using constant pH molecular dynamics and a reference
binding free energy that is taken either from experiment or from thermodynamic
integration computations, the pH-dependent binding free energy is determined.
This computational protocol accurately captures the large pKa shifts observed
experimentally upon CB[7]:guest association and reproduces experimental binding
free energies at different levels of pH. We show that incorrect assignment of
fixed protonation states in free energy computations can give errors of >2
kcal/mol in these host-guest systems. Use of the methods presented here avoids
such errors, thus suggesting their utility in computing proton-linked binding
free energies for protein-ligand complexes.
PMID- 25134694
TI - Comment on "Effects of ethanol on vehicle energy efficiency and implications on
ethanol life-cycle greenhouse gas analysis".
PMID- 25134693
TI - Tasmanian Aborigines step up to health: evaluation of a cardiopulmonary
rehabilitation and secondary prevention program.
AB - BACKGROUND: Although the burden of cardiopulmonary diseases in the Aboriginal
community is high, utilisation of rehabilitation services has been poor. We
evaluated the uptake and effectiveness of a cardiovascular and pulmonary
rehabilitation program specifically designed and provided for the Aboriginal
community, by the Tasmanian Aboriginal Centre, for people with diagnosed chronic
heart or respiratory disease and those at high risk of developing such
conditions. METHODS: Participants had established chronic obstructive pulmonary
disease, ischaemic heart disease or chronic heart failure or were at high risk of
developing such diseases because of multiple risk factors. Rehabilitation
programs (n = 13) comprised two exercise and one education session per week over
eight weeks. Data, collected at baseline and on completion, included health
status, risk factors, attendance, anthropometric measurements, physical capacity
and quality of life. Data from participants who attended at least one program
session were analysed. Qualitative written feedback from participants and staff
was analysed thematically. RESULTS: Of 92 participants (39% with an established
disease diagnosis), 72 provided follow-up data. Participants lost weight, and
waist circumference decreased (mean -3.6 cm, 95% confidence interval (CI)-2.5 to
4.7). There were clinically significant improvements in six-minute walk distance
(mean 55.7 m, 95% CI 37.8 to 73.7) and incremental shuttle walk (mean 106.2 m,
95% CI 79.1 to 133.2). There were clinically significant improvements in generic
quality of life domains, dyspnoea and fatigue. Generally, the improvements in
participants with established cardiac or respiratory diseases did not differ from
that in people with risk factors. Analysis of qualitative data identified three
factors that facilitated participation: support from peers and health workers,
provision of transport and the program structure. Participants' awareness of
improvements in their health contributed to ongoing participation and positive
health outcomes, and participants would recommend the program to family and
friends. CONCLUSION: A cardiopulmonary program, which included exercise and
education and met national guidelines, was designed and delivered specifically
for the Aboriginal community. It increased participation in rehabilitation by
Aborigines with, or at high risk of, established disease and led to positive
changes in health behaviours, functional exercise capacity and health related
quality of life.
PMID- 25134692
TI - Technology-assisted weight loss interventions in primary care: a systematic
review.
AB - BACKGROUND: The US Preventive Services Task Force recommends screening for and
treating obesity. However, there are many barriers to successfully treating
obesity in primary care (PC). Technology-assisted weight loss interventions offer
novel ways of improving treatment, but trials are overwhelmingly conducted
outside of PC and may not translate well into this setting. We conducted a
systematic review of technology-assisted weight loss interventions specifically
tested in PC settings. METHODS: We searched the literature from January 2000 to
March 2014. INCLUSION CRITERIA: (1) Randomized controlled trial; (2) trials that
utilized the Internet, personal computer, and/or mobile device; and (3) occurred
in an ambulatory PC setting. We applied the Cochrane Effective Practice and
Organization of Care (EPOC) and Delphi criteria to assess bias and the Pragmatic
Explanatory Continuum Indicator Summary (PRECIS) criteria to assess pragmatism
(whether trials occurred in the real world versus under ideal circumstances).
Given heterogeneity, results were not pooled quantitatively. RESULTS: Sixteen
trials met inclusion criteria. Twelve (75 %) interventions achieved weight loss
(range: 0.08 kg - 5.4 kg) compared to controls, while 5-45 % of patients lost at
least 5 % of baseline weight. Trial duration and attrition ranged from 3-36
months and 6-80 %, respectively. Ten (63 %) studies reported results after at
least 1 year of follow-up. Interventions used various forms of personnel,
technology modalities, and behavior change elements; trials most frequently
utilized medical doctors (MDs) (44 %), web-based applications (63 %), and self
monitoring (81 %), respectively. Interventions that included clinician-guiding
software or feedback from personnel appeared to promote more weight loss than
fully automated interventions. Only two (13 %) studies used publically available
technologies. Many studies had fair pragmatism scores (mean: 2.8/4), despite
occurring in primary care. DISCUSSION: Compared to usual care, technology
assisted interventions in the PC setting help patients achieve weight loss,
offering evidence-based options to PC providers. However, best practices remain
undetermined. Despite occurring in PC, studies often fall short in utilizing
pragmatic methodology and rarely provide publically available technology.
Longitudinal, pragmatic, interdisciplinary, and open-source interventions are
needed.
PMID- 25134695
TI - A joint history of the nature of genetic variation and the nature of
schizophrenia.
AB - This essay traces the history of concepts of genetic variation and schizophrenia
from Darwin and Mendel to the present. For Darwin, the important form of genetic
variation for evolution is continuous in nature and small in effect.
Biometricians led by Pearson agreed and developed statistical genetic approaches
utilizing trait correlations in relatives. Mendel studied discontinuous traits
and subsequent Mendelians, led by Bateson, assumed that important genetic
variation was large in effect producing discontinuous phenotypes. Although
biometricians studied 'insanity', schizophrenia genetics under Kraepelin and
Rudin utilized Mendelian approaches congruent with their anatomical-clinical
disease model of dementia praecox. Fisher showed, assuming many genes of small
effect, Mendelian and Biometrical models were consilient. Echoing prior
conflicts, psychiatric genetics since then has utilized both biometrical models,
largely in twins, and Mendelian models, based on advancing molecular techniques.
In 1968, Gottesman proposed a polygenic model for schizophrenia based on a
threshold version of Fisher's theory. Since then, rigorous studies of the
schizophrenia spectrum suggest that genetic risk for schizophrenia is more likely
continuous than categorical. The last 5 years has seen increasingly convincing
evidence from genome-wide association study (GWAS) and sequencing that genetic
risk for schizophrenia is largely polygenic, and congruent with Fisher's and
Gottesman's models. The gap between biometrical and molecular Mendelian models
for schizophrenia has largely closed. The efforts to ground a categorical
biomedical model of schizophrenia in Mendelian genetics have failed. The genetic
risk for schizophrenia is widely distributed in human populations so that we all
carry some degree of risk.
PMID- 25134703
TI - Neuro-oncology: It takes two to tango.
PMID- 25134696
TI - High prevalence of Toxoplasma gondii antibodies in dogs in Veracruz, Mexico.
AB - BACKGROUND: Little is known concerning the prevalence of Toxoplasma gondii
infection in dogs in Mexico. Here, we investigated antibodies to T. gondii and
associated risk factors in 101 dogs from an animal shelter in Veracruz State,
Mexico. Canine sera were assayed for T. gondii IgG antibodies by using the
modified agglutination test (MAT, cut off 1:25). RESULTS: Sixty eight (67.3%) of
101 dogs were seropositive with titers of 1:25 in 16, 1:50 in 8, 1:100 in 9,
1:200 in 10, 1:400 in 10, 1:800 in 10, 1:1600 in 3, and 1:3200 or higher in 2.
None of the dogs' characteristics studied including age, sex, breed, and history
of deworming, rabies vaccination and contact with cats was associated with
seroprevalence of T. gondii infection. CONCLUSION: Using the dogs as sentinel
animals, the results indicate high contamination with T. gondii of the
environment in Veracruz, Mexico. Results have public health implications, and
further studies in Veracruz should be conducted to establish the sources of
environmental contamination with T. gondii and to determine optimal preventive
measures against T. gondii infection in humans.
PMID- 25134706
TI - Alzheimer disease: Functional connectivity changes show similar trajectories in
autosomal dominant and sporadic Alzheimer disease.
PMID- 25134709
TI - Parkinson disease: Can a new trial end controversy over when to use levodopa?
AB - Levodopa is the standard therapy for Parkinson disease, but prolonged use
promotes the development of adverse motor effects. A new trial compared the
effectiveness of levodopa administration early in the disease with therapies that
used alternative dopaminergic agents before levodopa. No clinically relevant
differences were found between the treatment strategies.
PMID- 25134708
TI - Mechanism-based treatment in complex regional pain syndromes.
AB - Complex regional pain syndromes (CRPS) are multifactorial disorders with complex
aetiology and pathogenesis. Management of CRPS is challenging, partly because of
a lack of clinical data regarding the efficacy of the various therapies, and
partly because successful treatment of CRPS requires a multidisciplinary, patient
tailored approach. The pain in CRPS is often described as typical 'burning'
neuropathic pain, and is accompanied by a variety of sensory, motor and autonomic
signs and symptoms. Because research into therapies specifically in CRPS has been
scarce, treatment for these syndromes has been largely based on therapeutic
strategies adapted from neuropathic pain states; however, increased understanding
of the pathogenesis of CRPS has provided the opportunity to develop mechanism
based treatments. The interactions between the multiple pathophysiological
mechanisms that contribute to the development, progression and maintenance of
CRPS remain poorly understood. This Review describes the challenges in linking
the current theories and knowledge of pathophysiological mechanisms to the mode
of actions of the different treatment approaches. We discuss the current
treatment strategies for CRPS, including pharmacotherapy, sympathetic ganglion
block interventions, psychological support, physiotherapy and occupational
therapy, and establish the concept of mechanism-based treatment for CRPS.
PMID- 25134717
TI - Why it is scientifically respectable to believe in repression: a response to
Patihis, Ho, Tingen, Lilienfeld, and Loftus (2014).
PMID- 25134716
TI - Unconscious repressed memory is scientifically questionable.
PMID- 25134715
TI - The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility.
AB - The interplay between long-term potentiation and long-term depression (LTD) is
thought to be involved in learning and memory formation. One form of LTD
expressed in the hippocampus is initiated by the activation of the group 1
metabotropic glutamate receptors (mGluRs). Importantly, mGluRs have been shown to
be critical for acquisition of new memories and for reversal learning, processes
that are thought to be crucial for cognitive flexibility. Here we provide
evidence that MAPK-activated protein kinases 2 and 3 (MK2/3) regulate neuronal
spine morphology, synaptic transmission and plasticity. Furthermore, mGluR-LTD is
impaired in the hippocampus of MK2/3 double knockout (DKO) mice, an observation
that is mirrored by deficits in endocytosis of GluA1 subunits. Consistent with
compromised mGluR-LTD, MK2/3 DKO mice have distinctive deficits in hippocampal
dependent spatial reversal learning. These novel findings demonstrate that the
MK2/3 cascade plays a strategic role in controlling synaptic plasticity and
cognition.
PMID- 25134719
TI - Digital necrosis after triamcinolone acetonide injection for trigger thumb: case
report.
PMID- 25134718
TI - Analysis of high fat diet induced genes during mammary gland development:
identifying role players in poor prognosis of breast cancer.
AB - BACKGROUND: Epidemiological studies have shown that consumption of a high-fat
diet (HFD) increases the risk of developing breast cancer (BC). Studies in
rodents have shown HFD causes changes in the genetic programming of the maturing
mammary gland (MG) increasing the susceptibility of developing the disease. Less
is known about how HFD induced genes impact BC development. HFD exposure two
weeks before conception to six weeks of age was previously shown to dramatically
change MG gene expression in 10 week old mice. Therefore, we investigated these
differentially expressed HFD-induced genes for their expression in BC using the
NKI 295 breast tumor dataset. RESULTS: To examine the potential role of HFD
induced genes in BC, we first investigated whether these HFD-induced genes in
mouse MGs were differentially expressed in different types of human BC. Of the 28
HFD induced genes that were differentially expressed between BC subtypes in the
NKI set, 79% were significantly higher in basal-like BC. Next, we analyzed
whether HFD induced genes were associated with BC prognosis utilizing gene
expression and survival data for each HFD induced gene from the NKI data and
constructed Kaplan Meier survival plots. Significantly, 93% of the prognosis
associated genes (13/14) were associated with poor prognosis (P = 0.002). Kaplan
Meier analysis with 249 non-basal-like BC found that all but one of the genes
examined were still significantly associated with poor prognosis. Furthermore,
gene set enrichment analysis (GSEA) with HFD microarray data revealed that
invasive BC genes where enriched in HFD samples that also had lost expression of
luminal genes. CONCLUSIONS: HFD exposed mouse MGs maintain differential
expression of genes that are found highly expressed in basal-like breast cancer.
These HFD-induced genes associate with poor survival in numerous BC subtypes,
making them more likely to directly impact prognosis. Furthermore, HFD exposure
leads to a loss in the expression of luminal genes and a gain in expression of
mesenchymal and BC invasion genes in MGs. Collectively, our study suggests that
HFD exposure during development induces genes associated with poor prognosis,
thus identifying how HFD diet may regulate BC development.
PMID- 25134720
TI - Candida haemulonii complex: species identification and antifungal susceptibility
profiles of clinical isolates from Brazil.
AB - OBJECTIVES: The emerging fungal pathogens comprising the Candida haemulonii
complex (Candida haemulonii, Candida haemulonii var. vulnera and Candida
duobushaemulonii) are notable for their antifungal resistance. Twelve isolates
with phenotypic similarity to C. haemulonii were recovered from patients in
Brazilian hospitals. Here we aimed to identify these isolates by a molecular
approach, using the current classification of this fungal complex, and to
evaluate their antifungal susceptibility profiles. METHODS: The fungal isolates
were rechecked to certify their authentication by mycology methodologies and then
characterized by ITS1-5.8S-ITS2 gene sequencing. A susceptibility assay was
performed using the broth microdilution method published by CLSI (M27-A3/M27-S3).
RESULTS: Based on biochemical tests, all Brazilian isolates were identified as C.
haemulonii. After employing ITS sequencing, five isolates were identified as C.
haemulonii, four as C. duobushaemulonii and three as C. haemulonii var. vulnera.
All 12 clinical isolates were resistant to amphotericin B (MICs ranged from 2 to
>16 mg/L) and fluconazole (MICs >= 64 mg/L). One isolate of C. haemulonii var.
vulnera and two isolates of C. duobushaemulonii were susceptible-dose dependent
to itraconazole, while the remaining isolates (75%) were resistant to this
antifungal. Eight out of 12 isolates (66.7%) were resistant to voriconazole (MICs
>= 16 mg/L), while all isolates were susceptible to caspofungin (MICs <= 0.5
mg/L). CONCLUSIONS: Our results reinforce the importance of molecular
identification in differentiating species of the C. haemulonii complex. Moreover,
the antifungal multiresistant profile of clinical isolates of the C. haemulonii
complex represents a challenge to the treatment of such infections.
PMID- 25134721
TI - Activity of the type I signal peptidase inhibitor MD3 against multidrug-resistant
Gram-negative bacteria alone and in combination with colistin.
AB - OBJECTIVES: Effective treatment of Gram-negative bacterial infections is
increasingly challenging due to the spread of multidrug-resistant strains and a
lack of new antimicrobials in development. Bacterial type I signal peptidases
(SPases) represent a highly conserved and essential target for inhibition by
novel compounds. SPases are required for the effective processing of membrane
translocated proteins involved in core functions related to metabolism, virulence
and resistance. In this study we assessed the biochemical and functional activity
of a novel synthetic inhibitor (MD3) of SPases against a wide range of Gram
negative pathogens. METHODS: The activity and specificity of MD3 for recombinant
Pseudomonas aeruginosa SPase (LepB) and a genetically engineered LepB-regulatable
strain were investigated. Antimicrobial activity of the compound alone and in
combination with outer membrane-permeabilizing agents (sodium hexametaphosphate,
colistin) was also determined against a collection of P. aeruginosa,
Acinetobacter baumannii, Klebsiella pneumoniae and Stenotrophomonas maltophilia
isolates. RESULTS: MD3 was found to inactivate the P. aeruginosa LepB protein
(IC50 10 MUM), resulting in antimicrobial effects potentiated in the presence of
colistin. MD3 also demonstrated potent activity against wild-type and multidrug
resistant strains of A. baumannii and S. maltophilia with MICs ranging from 0.5
to 14 mg/L in the presence of subinhibitory concentrations of colistin.
CONCLUSIONS: MD3 is a novel inhibitor of bacterial SPase in a range of non
fermentative Gram-negative bacteria. The antimicrobial activity is potentiated in
combination with colistin and suggests that SPase inhibition warrants further
exploration as a basis for future mono or combination therapies.
PMID- 25134722
TI - Consumption of highly processed snacks, sugar-sweetened beverages and child
feeding practices in a rural area of Nicaragua.
AB - Appropriate feeding behaviours are important for child growth and development. In
societies undergoing nutrition transition, new food items are introduced that may
be unfavourable for child health. Set in rural Nicaragua, the aim of this study
was to describe the infant and young child feeding (IYCF) practices as well as
the consumption of highly processed snack foods (HP snacks) and sugar-sweetened
beverages (SSBs). All households with at least one child 0- to 35-month-old (n =
1371) were visited to collect information on current IYCF practices in the
youngest child as well as consumption of SSBs and HP snacks. Breastfeeding was
dominant (98%) among 0- to 1-month-olds and continued to be prevalent (60%) in
the second year, while only 34% of the 0- to 5-month-olds were exclusively
breastfed. Complementary feeding practices were deemed acceptable for only 59% of
the 6- to 11-month-old infants, with low dietary diversity reported for 50% and
inadequate meal frequency reported for 30%. Consumption of HP snacks and SSBs was
frequent and started early; among 6- to 8-month-olds, 42% and 32% had consumed HP
snacks and SSBs, respectively. The difference between the observed IYCF
behaviours and World Health Organization recommendations raises concern of
increased risk of infections and insufficient intake of micronutrients that may
impair linear growth. The concurrent high consumption of SSBs and HP snacks may
increase the risk of displacing the recommended feeding behaviours. To promote
immediate and long-term health, growth and development, there is a need to both
promote recommended IYCF practices as well as discourage unfavourable feeding
behaviours.
PMID- 25134724
TI - Early investigational drugs that target epidermal growth factor receptors for the
treatment of head and neck cancer.
AB - INTRODUCTION: Squamous-cell carcinoma of the head and neck (SCCHN) remains a
challenging clinical problem, due to the persistent high rate of local and
distant failures and the occurrence of secondary primaries. For locally advanced
SCCHN, a combination of chemotherapy (CT), radiation or surgery is often used,
but there are limitations, which may reduce compliance. Molecular targeted
therapies, namely anti-EGFR treatments, are in development with the aim of
improving clinical outcomes and mitigating treatment-related toxicities. AREAS
COVERED: This review provides an overview of early investigational drugs that
target EGFR for the treatment of SCCHN and discusses the ongoing trials in this
domain. EXPERT OPINION: Targeted therapies are increasingly used in oncology,
especially in SCCHN. Cetuximab has demonstrated a significant improvement in the
treatment outcome, both as a curative treatment in combination with radiation
therapy and as a palliative treatment in combination with CT; however, it failed
to show any benefit in combination with concomitant chemoradiotherapy. Presently,
there are many new agents, including monoclonal antibodies and small-molecule
tyrosine kinase inhibitors, which are either currently under investigation for or
which warrant further investigation for treating SCCHN. The discovery of
predictive factors that help to identify patients most likely to respond to EGFR
inhibitors as well as patient-customized therapies would help to improve patient
outcomes in the future.
PMID- 25134725
TI - Unified theory of electron-phonon renormalization and phonon-assisted optical
absorption.
AB - We present a theory of electronic excitation energies and optical absorption
spectra which incorporates energy-level renormalization and phonon-assisted
optical absorption within a unified framework. Using time-independent
perturbation theory we show how the standard approaches for studying vibronic
effects in molecules and those for addressing electron-phonon interactions in
solids correspond to slightly different choices for the non-interacting
Hamiltonian. Our present approach naturally leads to the Allen-Heine theory of
temperature-dependent energy levels, the Franck-Condon principle, the Herzberg
Teller effect and to phonon-assisted optical absorption in indirect band gap
materials. In addition, our theory predicts sub-gap phonon-assisted optical
absorption in direct gap materials, as well as an exponential edge which we
tentatively assign to the Urbach tail. We also consider a semiclassical approach
to the calculation of optical absorption spectra which simultaneously captures
energy-level renormalization and phonon-assisted transitions and is especially
suited to first-principles electronic structure calculations. We demonstrate this
approach by calculating the phonon-assisted optical absorption spectrum of bulk
silicon.
PMID- 25134723
TI - The ceramide kinase inhibitor NVP-231 inhibits breast and lung cancer cell
proliferation by inducing M phase arrest and subsequent cell death.
AB - BACKGROUND AND PURPOSE: Ceramide kinase (CerK) catalyzes the generation of
ceramide-1-phosphate which may regulate various cellular functions, including
inflammatory reactions and cell growth. Here, we studied the effect of a recently
developed CerK inhibitor, NVP-231, on cancer cell proliferation and viability and
investigated the role of cell cycle regulators implicated in these responses.
EXPERIMENTAL APPROACH: The breast and lung cancer cell lines MCF-7 and NCI-H358
were treated with increasing concentrations of NVP-231 and DNA synthesis, colony
formation and cell death were determined. Flow cytometry was performed to analyse
cell cycle distribution of cells and Western blot analysis was used to detect
changes in cell cycle regulator expression and activation. KEY RESULTS: In both
cell lines, NVP-231 concentration-dependently reduced cell viability, DNA
synthesis and colony formation. Moreover it induced apoptosis, as measured by
increased DNA fragmentation and caspase-3 and caspase-9 cleavage. Cell cycle
analysis revealed that NVP-231 decreased the number of cells in S phase and
induced M phase arrest with an increased mitotic index, as determined by
increased histone H3 phosphorylation. The effect on the cell cycle was even more
pronounced when NVP-231 treatment was combined with staurosporine. Finally,
overexpression of CerK protected, whereas down-regulation of CerK with siRNA
sensitized, cells for staurosporine-induced apoptosis. CONCLUSIONS AND
IMPLICATIONS: Our data demonstrate for the first time a crucial role for CerK in
the M phase control in cancer cells and suggest its targeted inhibition, using
drugs such as NVP-231, in combination with conventional pro-apoptotic
chemotherapy.
PMID- 25134726
TI - Graphene oxide amplifies the phytotoxicity of arsenic in wheat.
AB - Graphene oxide (GO) is widely used in various fields and is considered to be
relatively biocompatible. Herein, "indirect" nanotoxicity is first defined as
toxic amplification of toxicants or pollutants by nanomaterials. This work
revealed that GO greatly amplifies the phytotoxicity of arsenic (As), a
widespread contaminant, in wheat, for example, causing a decrease in biomass and
root numbers and increasing oxidative stress, which are thought to be regulated
by its metabolisms. Compared with As or GO alone, GO combined with As inhibited
the metabolism of carbohydrates, enhanced amino acid and secondary metabolism and
disrupted fatty acid metabolism and the urea cycle. GO also triggered damage to
cellular structures and electrolyte leakage and enhanced the uptake of GO and As.
Co-transport of GO-loading As and transformation of As(V) to high-toxicity
As(III) by GO were observed. The generation of dimethylarsinate, produced from
the detoxification of inorganic As, was inhibited by GO in plants. GO also
regulated phosphate transporter gene expression and arsenate reductase activity
to influence the uptake and transformation of As, respectively. Moreover, the
above effects of GO were concentration dependent. Given the widespread exposure
to As in agriculture, the indirect nanotoxicity of GO should be carefully
considered in food safety.
PMID- 25134727
TI - Amyloid-beta oligomers as a template for secondary amyloidosis in Alzheimer's
disease.
AB - Alzheimer's disease is a complex disease characterized by overlapping phenotypes
with different neurodegenerative disorders. Oligomers are considered the most
toxic species in amyloid pathologies. We examined human AD brain samples using an
anti-oligomer antibody generated in our laboratory and detected potential hybrid
oligomers composed of amyloid-beta, prion protein, alpha-synuclein, and TDP-43
phosphorylated at serines 409 and 410. These data and in vitro results suggest
that Abeta oligomer seeds act as a template for the aggregation of other proteins
and generate an overlapping phenotype with other neuronal disorders. Furthermore,
these results could explain why anti-amyloid-beta therapy has been unsuccessful.
PMID- 25134729
TI - Phosphorylated tau potentiates Abeta-induced mitochondrial damage in mature
neurons.
AB - Tau phosphorylated at the PHF-1 epitope (S396/S404) is likely involved in the
pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by
which tau phosphorylated at these sites negatively impacts neuronal functions are
still under scrutiny. Previously, we showed that expression of tau truncated at
D421 enhances mitochondrial dysfunction induced by Abeta in cortical neurons. To
extend these findings, we expressed tau pseudo-phosphorylated at S396/404 (T42EC)
in mature and young cortical neurons and evaluated different aspects of
mitochondrial function in response to Abeta. Expression of T42EC did not induce
significant changes in mitochondrial morphology, mitochondrial length, or
mitochondrial transport, compared to GFP and full-length tau. However, T42EC
expression enhanced Abeta-induced mitochondrial membrane potential loss and
increased superoxide levels compared to what was observed in mature neurons
expressing full-length tau. The same effect was observed in mature neurons that
expressed both pseudo-phosphorylated and truncated tau when they were treated
with Abeta. Interestingly, the mitochondrial failure induced by Abeta in mature
neurons that expressed T42EC, was not observed in young neurons expressing T42EC.
These novel findings suggest that phosphorylated tau (PHF-1 epitope) enhances
Abeta-induced mitochondrial injury, which contributes to neuronal dysfunction and
to the pathogenesis of AD.
PMID- 25134730
TI - Dynamic changes in pro- and anti-inflammatory cytokines in microglia after PPAR
gamma agonist neuroprotective treatment in the MPTPp mouse model of progressive
Parkinson's disease.
AB - Neuroinflammatory changes play a pivotal role in the progression of Parkinson's
disease (PD) pathogenesis. Recent findings have suggested that activated
microglia may polarize similarly to peripheral macrophages in the central nervous
system (CNS), assuming a pro-inflammatory M1 phenotype or the alternative anti
inflammatory M2 phenotype via cytokine production. A skewed M1 activation over M2
has been related to disease progression in Alzheimer disease, and modulation of
microglia polarization may be a therapeutic target for neuroprotection. By using
the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-probenecid (MPTPp) mouse model
of progressive PD, we investigated dynamic changes in the production of pro
inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and interleukin
(IL)-1beta, and anti-inflammatory cytokines, such as transforming growth factor
(TGF)-beta and IL-10, within Iba-1-positive cells in the substantia nigra
compacta (SNc). In addition, to further characterize changes in the M2 phenotype,
we measured CD206 in microglia. Moreover, in order to target microglia
polarization, we evaluated the effect of the peroxisome-proliferator-activated
receptor (PPAR)-gamma agonist rosiglitazone, which has been shown to exert
neuroprotective effects on nigral dopaminergic neurons in PD models, and acts as
a modulator of cytokine production and phenotype in peripheral macrophages.
Chronic treatment with MPTPp induced a progressive degeneration of SNc neurons.
The neurotoxin treatment was associated with a gradual increase in both TNF-alpha
and IL-1beta colocalization with Iba-1-positive cells, suggesting an increase in
pro-inflammatory microglia. In contrast, TGF-beta colocalization was reduced by
the neurotoxin treatment, while IL-10 was mostly unchanged. Administration of
rosiglitazone during the full duration of MPTPp treatment reverted both TNF-alpha
and IL-1beta colocalization with Iba-1 to control levels. Moreover, rosiglitazone
induced an increase in TGF-beta and IL-10 colocalization compared with the MPTPp
treatment. CD206 was gradually reduced by the chronic MPTPp treatment, while
rosiglitazone restored control levels, suggesting that M2 anti-inflammatory
microglia were stimulated and inflammatory microglia were inhibited by the
neuroprotective treatment. The results show that the dopaminergic degeneration
was associated with a gradual microglia polarization to the inflammatory over the
anti-inflammatory phenotype in a chronic mouse model of PD. Neuroprotective
treatment with rosiglitazone modulated microglia polarization, boosting the M2
over the pro-inflammatory phenotype. PPAR-gamma agonists may offer a novel
approach to neuroprotection, acting as disease-modifying drugs through an
immunomodulatory action in the CNS.
PMID- 25134728
TI - Genetic rescue of CB1 receptors on medium spiny neurons prevents loss of
excitatory striatal synapses but not motor impairment in HD mice.
AB - Huntington's disease (HD) is caused by an expanded polyglutamine repeat in
huntingtin protein that disrupts synaptic function in specific neuronal
populations and results in characteristic motor, cognitive and affective
deficits. Histopathological hallmarks observed in both HD patients and genetic
mouse models include the reduced expression of synaptic proteins, reduced medium
spiny neuron (MSN) dendritic spine density and decreased frequency of spontaneous
excitatory post-synaptic currents (sEPSCs). Early down-regulation of cannabinoid
CB1 receptor expression on MSN (CB1(MSN)) is thought to participate in HD
pathogenesis. Here we present a cell-specific genetic rescue of CB1(MSN) in R6/2
mice and report that treatment prevents the reduction of excitatory synaptic
markers in the striatum (synaptophysin, vGLUT1 and vGLUT2), of dendritic spine
density on MSNs and of MSN sEPSCs, but does not prevent motor impairment. We
conclude that loss of excitatory striatal synapses in HD mice is controlled by
CB1(MSN) and can be uncoupled from the motor phenotype.
PMID- 25134732
TI - Thermoplastic properties of endodontic gutta-percha: a thermographic in vitro
study.
AB - INTRODUCTION: Endodontic gutta-percha undergoes deformation at temperatures above
65 degrees C. The temperature influence of heat carriers on gutta-percha cones
was investigated in vitro. METHODS: Six single-rooted extracted teeth were
embedded in resin and fixed. The root canals were prepared (ProFile; Dentsply
Maillefer, Ballaiques, Switzerland) to different tapers and bisected.
Thermographic images when heating the gutta-percha cones (Roeko, Langenau,
Germany) with a heat carrier (ML .12; SybronEndo, Orange, CA) at 1 and 5 mm from
the working length were made with an infrared thermal imaging camera (ThermaCam
P640; Flir Systems, Taby, Sweden). The device temperature was preset at 200
degrees C. The pixel temperature registered at the contact lines between the heat
carriers and gutta-percha cones in the thermographic images was recorded and
statistically described. RESULTS: A mean temperature ( degrees C) instability in
the heat carrier (324.96 +/- 46.10, minimum = 147.35, maximum = 474.13), a
temperature drop of the gutta-percha cones (159.52, +/- 37.57, min 67.64, max
259.04) at the measuring level, and a mean temperature penetration depth (mm)
equal or to higher than 65 degrees C (1.05 +/- 0.28, minimum = 0.20, maximum =
1.30) were recorded. No correlation between the penetration depth into the gutta
percha cones and applied temperatures, regardless of the size and/or taper, could
be established. CONCLUSIONS: Temperature discrepancies between the device preset
and achieved ones of the heat carriers was observed. Gutta-percha is a poor
thermal conductor, transports heat irregularly, and should be heated 1-2 mm from
the target area.
PMID- 25134733
TI - Autogenous premolar transplantation into artificial socket in maxillary lateral
incisor site.
AB - INTRODUCTION: Autogenous transplantation of a natural tooth to another site has
significant advantages over dental implants, particularly in cases of agenesis,
accidental tooth loss, or poor prognosis for the maintenance of tooth function.
METHODS: This report describes a case of autogenous premolar transplantation into
an artificial socket in the site of a missing maxillary lateral incisor in a 13
year-old girl. Clinical examination and radiography revealed tooth agenesis (#4,
#10, #13, and #20) and microdontia (#7). The occlusion and skeletal
maxillomandibular relations were normal. RESULTS: Tooth #29 was chosen for
transplantation into the site of tooth #10 because of its size, stage of root
formation, and possible closure of the spaces created by agenesis. CONCLUSIONS:
Autogenous transplantation is a feasible alternative to dental implants in cases
of tooth agenesis or tooth loss because of trauma. Autotransplantation was
indicated in this case because it ensures the natural (facial) growth of the
alveolar process and preserves the function of periodontal tissues. A
multidisciplinary approach (ie, combining techniques from different dental
specialties) was important for treatment success. Clinical and radiographic
follow-up confirmed that the transplanted premolar was esthetically comparable
with the lateral incisor and that root development and pulp canal obliteration
were complete.
PMID- 25134731
TI - Guanabenz, which enhances the unfolded protein response, ameliorates mutant SOD1
induced amyotrophic lateral sclerosis.
AB - Approximately 20% of familial amyotrophic lateral sclerosis (FALS) cases are
caused by mutant superoxide dismutase type 1 (mtSOD1). Although the mechanisms of
mtSOD1-induced toxicity remain poorly understood, evidence suggests that
accumulation of misfolded SOD1 is fundamental to its toxicity and the death of
motor neurons. Misfolded mtSOD1 can accumulate inside the endoplasmic reticulum
(ER), leading to ER stress, with activation of the unfolded protein response
(UPR). We have previously carried out genetic studies focused on PERK (which is
an eIF2alpha kinase that is rapidly activated in response to ER stress and leads
to a repression in translation) and GADD34 (which participates in the
dephosphorylation of eIF2alpha). We reported that mtSOD1 transgenic mice that are
haploinsufficient for PERK have a significantly accelerated ALS disease, while
mtSOD1 mice that are mutated for GADD34 have a remarkably ameliorated disease.
Guanabenz, a centrally acting oral drug approved for the treatment of
hypertension, enhances the PERK pathway by selectively inhibiting GADD34-mediated
dephosphorylation of eIF2alpha. We have now treated G93A mtSOD1 transgenic mice
with guanabenz and found a significant amelioration of disease with a delay in
the onset and prolongation of the early phase of disease and survival. Guanabenz
treated G93A mice have less accumulation of mtSOD1 and an enhanced
phosphorylation of eIF2alpha at endstage. This study further emphasizes the
importance of the PERK pathway in the pathogenesis of FALS and as a therapeutic
target in ALS, and identifies guanabenz as a candidate drug for the treatment of
ALS patients.
PMID- 25134734
TI - Effects of WNT10A on proliferation and differentiation of human dental pulp
cells.
AB - INTRODUCTION: Wingless-type MMTV integration site family, member 10A (WNT10A)
plays crucial roles in odontogenesis. The aim of this study was to investigate
the effects of WNT10A on human dental pulp cells (DPCs), which contain a mixed
population of cells, including stem and progenitor cells, and participate in
dentin repair or dentin-pulp regeneration. METHODS: Healthy human premolars
extracted for orthodontic reasons were used as a study model. The expression of
WNT10A protein in dental pulp was determined by immunohistochemistry. The
messenger RNA expression of WNT10A and Wnt-related genes was analyzed by
semiquantitative reverse-transcription polymerase chain reaction. DPCs were
enzymatically separated from pulp tissues, cultured, and passaged. The biological
effects of WNT10A on DPCs were investigated using recombinant lentivirus encoding
WNT10A complementary DNA. WNT10A-induced changes in DPC proliferation were
assessed by methyltetrazolium assay and flow cytometry. In order to determine the
effects of WNT10A on DPC differentiation, the activity of alkaline phosphatase
(ALP), an early marker of odontoblastic differentiation, was assessed using an
ALP activity assay kit, and the expression levels of odontoblast-specific genes,
including DSPP, DMP1, ALP, and COL1A1, were detected by quantitative polymerase
chain reaction and Western blot. RESULTS: WNT10A protein was clearly identified
in the cytoplasm of DPCs. Semiquantitative reverse-transcription polymerase chain
reaction indicated the expression of WNT10A and Wnt-related genes in pulp tissues
as well as in passaging DPCs. Lentiviral overexpression of WNT10A enhanced
proliferation of DPCs and down-regulated ALP activity and the expression of
odontoblast-specific genes. CONCLUSIONS: WNT10A promotes the proliferation of
DPCs and negatively regulates their odontoblastic differentiation.
PMID- 25134735
TI - Evolutionary dynamics of R2 retroelement and insertion inheritance in the genome
of bisexual and parthenogenetic Bacillus rossius populations (Insecta Phasmida).
AB - Theoretical and empirical studies have shown differential management of
transposable elements in organisms with different reproductive strategies. To
investigate this issue, we analysed the R2 retroelement structure and variability
in parthenogenetic and bisexual populations of Bacillus rossius stick insects, as
well as insertions inheritance in the offspring of parthenogenetic isolates and
of crosses. The B. rossius genome hosts a functional (R2Br(fun) ) and a
degenerate (R2Br(deg) ) element, their presence correlating with neither
reproductive strategies nor population distribution. The median-joining network
method indicated that R2Br(fun) duplicates through a multiple source model, while
R2Br(deg) is apparently still duplicating via a master gene model. Offspring
analyses showed that unisexual and bisexual offspring have a similar number of
R2Br-occupied sites. Multiple or recent shifts from gonochoric to parthenogenetic
reproduction may explain the observed data. Moreover, insertion frequency spectra
show that higher-frequency insertions in unisexual offspring significantly
outnumber those in bisexual offspring. This suggests that unisexual offspring
eliminate insertions with lower efficiency. A comparison with simulated insertion
frequencies shows that inherited insertions in unisexual and bisexual offspring
are significantly different from the expectation. On the whole, different
mechanisms of R2 elimination in unisexual vs bisexual offspring and a complex
interplay between recombination effectiveness, natural selection and time can
explain the observed data.
PMID- 25134737
TI - Memory processes in the development of reduced-salt foods.
AB - Acceptance of a reduced-salt food is likely to be influenced by a mismatch
between the sensory characteristics of a reformulated product and a memory for a
previously-encountered formulation. In two initial pilot studies we established
the reliability of a new measure of memory for saltiness, based on a method of
constant stimuli. We then used this technique to explore the effects of different
patterns of repeated exposure on memory for the taste of a reduced-salt soup.
Participants (N = 135) were assigned to one of four exposure patterns: (1)
reduced-salt, (2) no salt reduction, i.e. regular-salt, (3) reduced- and regular
salt, in an alternating pattern, and (4) gradually declining salt concentration.
In the final session, all participants received an identical reduced-salt soup.
Memory for the saltiness of this sample was assessed, together with its expected
liking. Our results indicate that different interactions with the test soup had
little effect on taste memory. Nevertheless, (1) participants remembered the
final exposure soup as saltier than the reduced-salt formulation that they had
received and (2) remembered salt concentrations correlated with individual ideal
salt concentrations. These findings are consistent with contemporary models of
reconstructive memory and they illustrate the importance of understanding 'memory
for saltiness' in the acceptance of reduced-salt formulations.
PMID- 25134736
TI - Interpersonal motives and social-evaluative threat: Effects of acceptance and
status stressors on cardiovascular reactivity and salivary cortisol response.
AB - Social-evaluative threat evokes increases in salivary cortisol and heightened
cardiovascular reactivity. However, the types or content of social threats
underlying these physiological responses are not clearly delineated in direct
comparisons. Based in interpersonal theory, the present study manipulated high
and low levels of acceptance threat (i.e., evaluation of likability, potential
for inclusion) and status threat (i.e., evaluation of competence, leadership
potential) during a modified Trier Social Stress Test, using a sample of 137
undergraduates (73 women). Both acceptance threat and status threat heightened
salivary cortisol, heart rate, and blood pressure responses to the task. Hence,
concerns about social inclusion or connection with others and concerns about
social standing or status can contribute independently to physiological stress
responses.
PMID- 25134738
TI - Bidirectional associations between binge eating and restriction in anorexia
nervosa. An ecological momentary assessment study.
AB - This study examined the association between restrictive eating behaviors and
binge eating in anorexia nervosa (AN) using data collected in the natural
environment. Women (N = 118) with DSM-IV full or subthreshold AN reported eating
disorder behaviors, including binge eating episodes, going >= 8 waking hours
without eating, and skipping meals, during 2 weeks of ecological momentary
assessment (EMA). Time-lagged generalized estimating equations tested the
following hypotheses: 1) dietary restriction would predict binge eating while
controlling for binge eating the previous day; 2) binge eating would predict
restriction the subsequent day while controlling for restriction the previous
day. After controlling for relevant covariates, the hypotheses were not
supported; however, there appeared to be a cumulative effect of repeatedly going
8 consecutive hours without eating (i.e. fasting) on the risk of binge eating
among individuals who recently engaged in binge eating. In addition, skipping
meals was associated with a lower risk of same day binge eating. The relationship
between binge eating and dietary restriction appears to be complex and may vary
by type of restrictive eating behavior. Future research should aim to further
clarify the nature of the interaction of binge eating and restrictive eating
among individuals with AN in order to effectively eliminate these behaviors in
treatment.
PMID- 25134741
TI - Knee arthrotomy closure with barbed suture in flexion versus extension: a porcine
study.
AB - The purpose of this biomechanical study was to evaluate knee arthrotomy closure
with a barbed suture in flexion versus extension. 48 porcine knees were
randomized into three groups: full extension, 30 degrees flexion, and 60 degrees
flexion. Each knee was then flexed to 90 degrees and then 120 degrees , with
failures recorded. Arthrotomy closure in extension had significantly higher
failure rates (6/16) upon flexion to 90 degrees compared to arthrotomy closure
in either 30 degrees or 60 degrees flexion (0/32) (P = 0.032). Upon ranging
from 0 degrees to 120 degrees , arthrotomy failure occurred in 50% (8/16) of
arthrotomies in the extension group, 6.25% (1/16) in the 30 degrees flexion
group and 18.75% (3/16) in the 60 degrees flexion group (P = 0.022). Knee
arthrotomy closure in extension compared to flexion had significantly higher
rates of failure.
PMID- 25134742
TI - Proximal femoral arthroplasty in patients undergoing revision hip arthroplasty.
AB - Bone loss represents one of the greatest challenges in revision joint surgery. A
retrospective review was conducted of both radiographic and clinical outcomes of
eleven patients who underwent revision arthroplasty using a long extensively
porous coated cylindrical femoral component. All patients' femurs presented with
severe proximal femoral bone loss (Paprosky class IIIB and IV). With a mean
follow-up of 8 years (2 to 14) we report no femoral revisions and one acetabular
revision to a constrained cup secondary to instability. All patients were
clinically and radiographically stable. We did not observe any issue with
proximal stress shielding or component loosening. The article reports that in
patients with severe proximal femoral bone loss, extensively porous-coated non
modular stems are a viable option offering stable and predictable outcomes.
PMID- 25134740
TI - The role of family-related factors in the effects of the UP4FUN school-based
family-focused intervention targeting screen time in 10- to 12-year-old children:
the ENERGY project.
AB - BACKGROUND: Screen-related behaviours are highly prevalent in schoolchildren.
Considering the adverse health effects and the relation of obesity and screen
time in childhood, efforts to affect screen use in children are warranted.
Parents have been identified as an important influence on children's screen time
and therefore should be involved in prevention programmes. The aim was to examine
the mediating role of family-related factors on the effects of the school-based
family-focused UP4FUN intervention aimed at screen time in 10- to 12-year-old
European children (n child-parent dyads = 1940). METHODS: A randomised controlled
trial was conducted to test the six-week UP4FUN intervention in 10- to 12-year
old children and one of their parents in five European countries in 2011 (n child
parent dyads = 1940). Self-reported data of children were used to assess their TV
and computer/game console time per day, and parents reported their physical
activity, screen time and family-related factors associated with screen
behaviours (availability, permissiveness, monitoring, negotiation, rules,
avoiding negative role modeling, and frequency of physically active family
excursions). Mediation analyses were performed using multi-level regression
analyses (child-school-country). RESULTS: Almost all TV-specific and half of the
computer-specific family-related factors were associated with children's screen
time. However, the measured family-related factors did not mediate intervention
effects on children's TV and computer/game console use, because the intervention
was not successful in changing these family-related factors. CONCLUSION: Future
screen-related interventions should aim to effectively target the home
environment and parents' practices related to children's use of TV and computers
to decrease children's screen time. TRIAL REGISTRATION: The study is registered
in the International Standard Randomised Controlled Trial Number Register
(registration number: ISRCTN34562078).
PMID- 25134743
TI - Correlation between knee kinematics and patellofemoral contact pressure in total
knee arthroplasty.
AB - The aim of this study is to evaluate the relationship between patellofemoral
contact stress and intraoperative knee kinematic patterns after mobile bearing
total knee arthroplasty (TKA). Medial osteoarthritic knees of forty-six posterior
stabilized total knee prostheses were evaluated using a computed tomography
guided navigation system. Subjects were divided into two groups based on
intraoperative knee kinematic patterns: the medial pivot group (n=19) and the non
medial pivot group (n=27). Mean intraoperative patello-femoral contact stress was
significantly lower in the medial pivot group than in the non-medial pivot group
(1.7MPa vs. 3.2MPa, P<0.05). An intraoperative medial pivot pattern results in
reduced patello-femoral contact stress.
PMID- 25134739
TI - Signaling through retinoic acid receptors in cardiac development: Doing the right
things at the right times.
AB - Retinoic acid (RA) is a terpenoid that is synthesized from vitamin A/retinol
(ROL) and binds to the nuclear receptors retinoic acid receptor (RAR)/retinoid X
receptor (RXR) to control multiple developmental processes in vertebrates. The
available clinical and experimental data provide uncontested evidence for the
pleiotropic roles of RA signaling in development of multiple embryonic structures
and organs such eyes, central nervous system, gonads, lungs and heart. The
development of any of these above-mentioned embryonic organ systems can be
effectively utilized to showcase the many strategies utilized by RA signaling.
However, it is very likely that the strategies employed to transfer RA signals
during cardiac development comprise the majority of the relevant and
sophisticated ways through which retinoid signals can be conveyed in a complex
biological system. Here, we provide the reader with arguments indicating that RA
signaling is exquisitely regulated according to specific phases of cardiac
development and that RA signaling itself is one of the major regulators of the
timing of cardiac morphogenesis and differentiation. We will focus on the role of
signaling by RA receptors (RARs) in early phases of heart development. This
article is part of a Special Issue entitled: Nuclear receptors in animal
development.
PMID- 25134744
TI - Subtype and regional regulation of prion biomarkers in sporadic Creutzfeldt-Jakob
disease.
AB - AIMS: Creutzfeldt-Jakob disease (CJD) is a rapid progressive neurological disease
leading to dementia and death. Prion biomarkers are altered in the cerebrospinal
fluid (CSF) of CJD patients, but the pathogenic mechanisms underlying these
alterations are still unknown. The present study examined prion biomarker levels
in the brain and CSF of sporadic CJD (sCJD) cases and their correlation with
neuropathological lesion profiles. METHODS: The expression levels of 14-3-3, Tau,
phospho-Tau and alpha-synuclein were measured in the CSF and brain of sCJD cases
in a subtype- and region-specific manner. In addition, the activity of prion
biomarker kinases, the expression levels of CJD hallmarks and the most frequent
neuropathological sCJD findings were analysed. RESULTS: Prion biomarkers levels
were increased in the CSF of sCJD patients; however, correlations between mRNA,
total protein and their phosphorylated forms in brain were different. The
observed downregulation of the main Tau kinase, GSK3, in sCJD brain samples may
help to explain the differential phospho-Tau/Tau ratios between sCJD and other
dementias in the CSF. Importantly, CSF biomarkers levels do not necessarily
correlate with sCJD neuropathological findings. INTERPRETATION: Present findings
indicate that prion biomarkers levels in sCJD tissues and their release into the
CSF are differentially regulated following specific modulated responses, and
suggest a functional role for these proteins in sCJD pathogenesis.
PMID- 25134746
TI - Paralympic sports medicine and sports science--introduction.
PMID- 25134745
TI - Typology of sleep medication users and associated mental health and substance use
from a Montreal epidemiological study.
AB - BACKGROUND: Sleep medication is often reported as one of the most highly used
psychotropic drugs in terms of past-year prevalence. Since their use often varies
according to the characteristics of individuals, it is important to better
understand these particular utilization patterns. OBJECTIVES: The study aims to
develop a typology of sleep medication users' characteristics, including their
associated mental health and substance use. METHODS: Residents from the
epidemiological area of south-west Montreal, Quebec aged 15 years and older
responded to a questionnaire in 2009 and 2011. Among the 1822 people who
participated at both T1 and T2, 306 (17%) reported use of medication to help them
sleep. These participants were selected for cluster analysis based on five
variables related to mental health. The identified clusters were then tested for
association with sociodemographic, psychosocial, and service use characteristics.
RESULTS: A three-cluster solution emerged: 1) older individuals without mental
health problems, drug use or psychotropic medication use; 2) individuals with
elevated psychological distress, drug use and low social support, and 3)
individuals with mood and anxiety disorders, using services for mental health and
taking two or more psychotropic medications. CONCLUSIONS: The results establish
the significance of problems related to mental health in differentiating sleep
medication users. Consideration of these differences may improve the ability of
health professionals to provide services that are better suited for patients,
including interventions that increase the ability to cope with stress (cluster 2)
and more integrated services for those with concurrent disorders (cluster 3).
PMID- 25134747
TI - Paralympic classification: conceptual basis, current methods, and research
update.
AB - Paralympic classification systems aim to promote participation in sport by people
with disabilities by controlling for the impact of impairment on the outcome of
competition. Valid systems of classification ensure that successful athletes are
those who have the most advantageous combination of anthropometric,
physiological, and/or psychological attributes, and who have enhanced them to the
best effect. Classification systems that are not valid pose a significant threat
to Paralympic sport and, therefore, the International Paralympic Committee (IPC)
has a Classification Code which includes policy commitment to the development of
evidence-based methods of classification. The aim of this article is to provide
an overview of current best practice in classification for athletes with physical
impairments, and to update research advances in the area. Currently,
classification has 4 stages: (1) establish whether the athlete has a health
condition that will lead to one or more of the 8 eligible types of physical
impairment, (2) determine whether the athlete has an eligible impairment type,
(3) determine whether the impairment is severe enough, and (4) determine in what
class the athlete should compete. A sequential 4-step process that outlines how
to initiate and develop evidence-based methods of classification is described:
(1) specification of impairment types that are eligible for the sport; (2)
development of valid measures of impairment(s); (3) development of standardized,
sport-specific measures of performance; and (4) assessment of the relative
strength of association between measures of impairment and measures of
performance. Of these, the development and reporting of valid measures of
impairment is currently the most pressing scientific challenge in the development
of evidence-based methods of classification.
PMID- 25134749
TI - Clinical characteristics of 385 illnesses of athletes with impairment reported on
the WEB-IISS system during the London 2012 Paralympic Games.
AB - BACKGROUND: Prevention of illness is important for a team physician. However,
there are few studies that reported clinical aspects of illness of athletes with
impairment. OBJECTIVE: To describe the clinical characteristics of the 385
illnesses reported on the a novel Web-based electronic injury and illness
capturing system (WEB-IISS) during the London 2012 Paralympic Games. DESIGN: Part
of a large prospective cohort study. SETTING: London 2012 Paralympic Games.
PARTICIPANTS: Team physicians of 78 delegations (3329 athletes over 14 days) used
WEB-IISS. Each day, information was recorded, which included daily team size and
illness details, system affected, final diagnosis, type and onset of symptoms,
training and/or competition days lost, and suspected cause. MAIN OUTCOME
MEASUREMENT: Incidence of illness (illness per 1000 athlete days). RESULTS: The
incidence of illness in the cohort was 8.3 per 1000 (95% confidence interval, 7.5
9.1) athlete days, and the percentage of athletes with an illness in this study
was 9.2%. Respiratory system illnesses were the most common (39.4%), followed by
the digestive system (15.8%), skin and subcutaneous system (11.8%), genitourinary
system (8.8%), and nervous system (7.3%). Urinary tract illness was more common
in athletes with spinal cord injury (22%) compared with the athletes with other
impairments (0%-5%). Skin and subcutaneous illness varied from 0%-18% between
impairment categories and was highest for athletes with spinal cord injury.
Infections accounted for 40.8% of all illness and 19.5% of illness that resulted
in a time loss of >=1 day. In 34% of illnesses, symptoms were present for >=1 day
before being reported to the team physician. CONCLUSION: The majority of
illnesses affected the respiratory, gastrointestinal, skin and subcutaneous, and
genitourinary systems, and were mostly infective in nature. The highest number of
all illnesses, including skin and subcutaneous illnesses, and urinary tract
illnesses, were of athletes with spinal cord injury. Although most illnesses were
not time-loss illnesses, 19.5% of illnesses resulted in >=1 day lost. Team
physicians should be aware that, in many cases of infection reported, the
symptoms were already present the day before. A delay in reporting of symptoms
>24 hours could have important clinical implications for athletes' medical care.
PMID- 25134748
TI - Descriptive epidemiology of Paralympic sports injuries.
AB - Paralympic sports have seen an exponential increase in participation since 16
patients took part in the first Stoke Mandeville Games on the opening day of the
1948 London Olympic Games. More than 4,000 athletes took part in the London 2012
Paralympic Games. Few sporting events have seen such rapid evolution. This rapid
pace of change also has meant challenges for understanding the injury risks of
participation, not only because of the variety of sports, impairment types, the
evolution of adapted equipment but also because of the inclusion of additional
impairment types and development of new sports over time. Early studies were
limited in scope but patterns of injuries are slowly emerging within Winter and
Summer Paralympic sports. The IPC's London 2012 study is the largest to date with
a prospective cohort study involving 49,910 athlete-days. The results identified
large differences across sports and highlighted the need for longitudinal sport
specific studies rather than solely games-time studies. This will require
collaboration with international sports federations to examine injury patterns
and risk factors for injury in this population to appropriately inform injury
prevention strategies. Further studies will also need to address the impact of
sporting participation, injury, and future health.
PMID- 25134750
TI - Adaptive sports technology and biomechanics: wheelchairs.
AB - Wheelchair sports are an important tool in the rehabilitation of people with
severe chronic disabilities and have been a driving force for innovation in
technology and practice. In this paper, we will present an overview of the
adaptive technology used in Paralympic sports with a special focus on wheeled
technology and the impact of design on performance (defined as achieving the
greatest level of athletic ability and minimizing the risk of injury). Many
advances in manual wheelchairs trace their origins to wheelchair sports. Features
of wheelchairs that were used for racing and basketball 25 or more years ago have
become integral to the manual wheelchairs that people now use every day;
moreover, the current components used on ultralight wheelchairs also have
benefitted from technological advances developed for sports wheelchairs. For
example, the wheels now used on chairs for daily mobility incorporate many of the
components first developed for sports chairs. Also, advances in manufacturing and
the availability of aerospace materials have driven current wheelchair design and
manufacture. Basic principles of sports wheelchair design are universal across
sports and include fit; minimizing weight while maintaining high stiffness;
minimizing rolling resistance; and optimizing the sports-specific design of the
chair. However, a well-designed and fitted wheelchair is not sufficient for
optimal sports performance: the athlete must be well trained, skilled, and use
effective biomechanics because wheelchair athletes face some unique biomechanical
challenges.
PMID- 25134751
TI - From the Paralympics to public health: increasing physical activity through
legislative and policy initiatives.
AB - Individuals with disabilities experience a disproportionate rate of chronic
disease and are more likely to lead sedentary lifestyles than the general
population. Multiple complex factors likely contribute to these disparities,
including structural, socioeconomic and attitudinal barriers that impede broad
participation of individuals with disabilities in health and wellness promotion
programs. Public health initiatives aimed at mitigating these health disparities
emphasize improved access to physical activity and sports opportunities. Given
its visibility, the Paralympic Movement provides an opportunity to transform how
society conceptualizes the relationship of disability to physical fitness. The
Paralympics also serve as a catalyst for public health education and program
development. Already, public policies and governmental regulations are expanding
grassroots sports opportunities for youth and adults with disabilities, thus
promoting inclusive opportunities for participation in physical activity.
PMID- 25134752
TI - Adaptive sports technology and biomechanics: prosthetics.
AB - With the technologic advances in medicine and an emphasis on maintaining physical
fitness, the population of athletes with impairments is growing. It is incumbent
upon health care practitioners to make every effort to inform these individuals
of growing and diverse opportunities and to encourage safe exercise and athletic
participation through counseling and education. Given the opportunities for
participation in sports for persons with a limb deficiency, the demand for new,
innovative prosthetic designs is challenging the clinical and technical expertise
of the physician and prosthetist. When generating a prosthetic prescription,
physicians and prosthetists should consider the needs and preferences of the
athlete with limb deficiency, as well as the functional demands of the chosen
sporting activity. The intent of this article is to provide information regarding
the current advancements in the adaptive sports technology and biomechanics in
the field of prosthetics, and to assist clinicians and their patients in
facilitating participation in sporting activities.
PMID- 25134753
TI - The role of autonomic function on sport performance in athletes with spinal cord
injury.
AB - Devastating paralysis, autonomic dysfunction, and abnormal cardiovascular control
present significant hemodynamic challenges to individuals with spinal cord injury
(SCI), especially during exercise. In general, resting arterial pressure after
SCI is lower than with able-bodied individuals and is commonly associated with
persistent orthostatic intolerance along with transient episodes of life
threatening hypertension, known as "autonomic dysreflexia." During exercise, the
loss of central and reflexive cardiovascular control attenuates maximal heart
rate and impairs blood pressure regulation and blood redistribution, which
ultimately reduces venous return, stroke volume, and cardiac output.
Thermoregulation also is severely compromised in high-lesion SCI, a problem that
is compounded when competing in hot and humid conditions. There is some evidence
that enhancing venous return via lower body positive pressure or abdominal
binding improves exercise performance, as do cooling strategies. Athletes with
SCI also have been documented to self-induce autonomic dysreflexia before
competition with a view of increasing blood pressure and improving their
performance, a technique known as "boosting." For health safety reasons, boosting
is officially banned by the International Paralympics Committee. This article
addresses the complex issue of how the autonomic nervous system affects sports
performance in athletes with SCI, with a specific focus on the potential
debilitating effects of deranged cardiovascular control.
PMID- 25134754
TI - Ethical considerations in Paralympic sport: when are elective treatments
allowable to improve sports performance?
PMID- 25134755
TI - Stories from Sochi: sun, sea, snow, and salt.
PMID- 25134757
TI - DNA looping provides for "intersegmental hopping" by proteins: a mechanism for
long-range site localization.
AB - Studies on how transcription factors and DNA modifying enzymes passively locate
specific sites on DNA have yet to be reconciled with a sufficient set of
mechanisms that can adequately account for the efficiency and speed of this
process. This is especially true when considering that these DNA
binding/modifying proteins have diverse levels of both cellular copy numbers and
genomic recognition site densities. The monomeric bacterial DNA adenine
methyltransferase (Dam) is responsible for the rapid methylation of the entire
chromosome (with only ~100 Dam copies per cell) and the regulated methylation of
closely spaced sites that controls the expression of virulence genes in several
human pathogens. Provocatively, we find that Dam travels between its recognition
sites most efficiently when those sites are ~500bp apart. We propose that this is
manifested by Dam moving between distal regions on the same DNA molecule, which
is mediated by DNA looping, a phenomenon we designate as intersegmental hopping.
Importantly, an intermediate found in other systems including two simultaneously
bound, looped DNA strands is not involved here. Our results suggest that
intersegmental hopping contributes to enzymatic processivity (multiple
modifications), which invoke recent reports demonstrating that DNA looping can
assist in site finding. Intersegmental hopping is possibly used by other sequence
specific DNA binding proteins, such as transcription factors and regulatory
proteins, given certain biological context. While a general form of this
mechanism is proposed by many research groups, our consideration of DNA looping
in the context of processive catalysis provides new mechanistic insights and
distinctions.
PMID- 25134756
TI - Functional suppression of HAMP domain signaling defects in the E. coli serine
chemoreceptor.
AB - HAMP domains play key signaling roles in many bacterial receptor proteins. The
four-helix HAMP bundle of the homodimeric Escherichia coli serine chemoreceptor
(Tsr) interacts with an adjoining four-helix sensory adaptation bundle to
regulate the histidine autokinase CheA bound to the cytoplasmic tip of the Tsr
molecule. The adaptation helices undergo reversible covalent modifications that
tune the stimulus-responsive range of the receptor: unmodified E residues promote
kinase-off output, and methylated E residues or Q replacements at modification
sites promote kinase-on output. We used mutationally imposed adaptational
modification states and cells with various combinations of the sensory adaptation
enzymes, CheR and CheB, to characterize the signaling properties of mutant Tsr
receptors that had amino acid replacements in packing layer 3 of the HAMP bundle
and followed in vivo CheA activity with an assay based on Forster resonance
energy transfer. We found that an alanine or a serine replacement at HAMP residue
I229 effectively locked Tsr output in a kinase-on state, abrogating chemotactic
responses. A second amino acid replacement in the same HAMP packing layer
alleviated the I229A and I229S signaling defects. Receptors with the suppressor
changes alone mediated chemotaxis in adaptation-proficient cells but exhibited
altered sensitivity to serine stimuli. Two of the suppressors (S255E and S255A)
shifted Tsr output toward the kinase-off state, but two others (S255G and L256F)
shifted output toward a kinase-on state. The alleviation of locked-on defects by
on-shifted suppressors implies that Tsr-HAMP has several conformationally
distinct kinase-active output states and that HAMP signaling might involve
dynamic shifts over a range of bundle conformations.
PMID- 25134758
TI - Ryanodine receptors: allosteric ion channel giants.
AB - The endoplasmic reticulum (ER) and sarcoplasmic reticulum (SR) form major
intracellular Ca(2+) stores. Ryanodine receptors (RyRs) are large tetrameric ion
channels in the SR and ER membranes that can release Ca(2+) upon triggering. With
molecular masses exceeding 2.2MDa, they represent the pinnacle of ion channel
complexity. RyRs have adopted long-range allosteric mechanisms, with pore opening
resulting in conformational changes over 200A away. Together with tens of protein
and small molecule modulators, RyRs have adopted rich and complex regulatory
mechanisms. Structurally related to inositol-1,4,5-trisphosphate receptors
(IP3Rs), RyRs have been studied extensively using cryo-electron microscopy (cryo
EM). Along with more recent X-ray crystallographic analyses of individual
domains, these have resulted in pseudo-atomic models. Over 500 mutations in RyRs
have been linked to severe genetic disorders, which underscore their role in the
contraction of cardiac and skeletal muscles. Most of these have been linked to
gain-of-function phenotypes, resulting in premature or prolonged leak of Ca(2+)
in the cytosol. This review outlines our current knowledge on the structure of
RyRs at high and low resolutions, their relationship to IP3Rs, an overview of the
most commonly studied regulatory mechanisms, and models that relate disease
causing mutations to altered channel function.
PMID- 25134759
TI - Bezafibrate, a peroxisome proliferator-activated receptor alpha agonist,
decreases circulating CD14(+)CD16(+) monocytes in patients with type 2 diabetes.
AB - CD14(+)CD16(+) monocytes are proinflammatory cells that produce tumor necrosis
factor and interleukin (IL)-1beta. The number of circulating CD14(+)CD16(+)
monocytes is increased in patients with chronic renal failure or coronary artery
disease. We investigated the effect of bezafibrate, a peroxisome proliferator
activated receptor alpha agonist, on circulating CD14(+)CD16(+) monocytes in
patients with type 2 diabetes. Using cells isolated from type 2 diabetic
subjects, we also examined the in vitro expression of CD16 messenger RNA (mRNA)
by mononuclear cells (MNCs) exposed to bezafibrate. The percentage of
CD14(+)CD16(+) monocytes among all CD14(+) monocytes was significantly higher in
subjects with impaired glucose tolerance (P < 0.01) or type 2 diabetes (P < 0.05)
than in those with normal glucose tolerance. The percentage of CD14(+)CD16(+)
monocytes was significantly lower in patients with type 2 diabetes who were
taking bezafibrate (400 mg/d) than in patients not taking it (P < 0.01).
Treatment with bezafibrate for 12 weeks significantly reduced the percentage of
circulating CD14(+)CD16(+) monocytes from 45.4 +/- 25.2% to 38.3 +/- 21.8% (P =
0.0144). In an in vitro study, the expression of CD16 mRNA by MNCs from 6
diabetic subjects was decreased after 24 hours of treatment with 10 MUg/mL of
bezafibrate (P < 0.05). Expression of IL-1beta mRNA by MNCs was also decreased
after 24 hours of treatment with 10 MUg/mL of bezafibrate, whereas the IL-1beta
level in the culture supernatant was significantly decreased after treatment of
MNCs with either 1 or 10 MUg/mL of bezafibrate. In conclusion, bezafibrate
decreased circulating CD14(+)CD16(+) monocytes in patients with type 2 diabetes,
probably by inhibiting the expression of CD16 mRNA.
PMID- 25134761
TI - Synthesis and Toxicity Evaluation of Some N4-Aryl Substituted 5
Trifluoromethoxyisatin-3-thiosemicarbazones.
AB - A series of twenty one N4-aryl substituted 5-trifluoromethoxyisatin-3
thiosemicarbazones 3a-3u was synthesized by the reaction of
trifluoromethoxyisatin 1 with different arylthiosemicarbazides 2 in aqueous
ethanol (50%), containing a few drops of acetic acid. Their structures were
established on the basis of analytical (CHN) and spectral (IR, 1H-NMR, EIMS)
data. All the synthesized compounds were evaluated for their toxicity potential
by a brine shrimp lethality bioassay. Ten compounds i.e., 3a, 3e, 3i-3l and 3n-3q
proved to be active in this assay, displaying promising toxicity (LD50 = 1.11 *
10-5 M - 1.80 * 10-4 M). Amongst these, 3k, 3n and 3o were found to be the most
active ones (LD50 = 1.11 * 10-5 M - 1.43 * 10-5 M). Compound 3k showed the
highest activity with a LD50 value of 1.11 * 10-5 M and can, therefore, be used
as a lead for further studies. Structure-activity relationship (SAR) studies
revealed that the presence of strong inductively electron-attracting
trifluoromethoxy substituent at position-5 of the isatin moiety played an
important role in inducing or enhancing toxic potentiality of some of the
synthesized compounds.
PMID- 25134763
TI - Recent Advances in the Application of SelectfluorTM F-TEDA-BF4 as a Versatile
Mediator or Catalyst in Organic Synthesis.
AB - SelectfluorTM F-TEDA-BF4 (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo
[2.2.2]octane bis(tetrafluoroborate) is not only one of the most efficient and
popular reagents for electrophilic fluorination, but as a strong oxidant is also
a convenient mediator or catalyst of several "fluorine-free" functionalizations
of organic compounds. Its applications as a mediator in transformations of
oxidizable functional groups or gold-catalyzed C-C and C-heteroatom oxidative
coupling reactions, a catalyst in formation of various heterocyclic rings, a
reagent or catalyst of various functionalizations of electron-rich organic
compounds (iodination, bromination, chlorination, nitration, thiocyanation,
sulfenylation, alkylation, alkoxylation), a catalyst of one-pot-multi-component
coupling reactions, a catalyst of regioselective ring opening of epoxides, a
deprotection reagent for various protecting groups, and a mediator for
stereoselective rearrangement processes of bicyclic compounds are reviewed and
discussed.
PMID- 25134760
TI - Evidence that meningeal mast cells can worsen stroke pathology in mice.
AB - Stroke is the leading cause of adult disability and the fourth most common cause
of death in the United States. Inflammation is thought to play an important role
in stroke pathology, but the factors that promote inflammation in this setting
remain to be fully defined. An understudied but important factor is the role of
meningeal-located immune cells in modulating brain pathology. Although different
immune cells traffic through meningeal vessels en route to the brain, mature mast
cells do not circulate but are resident in the meninges. With the use of genetic
and cell transfer approaches in mice, we identified evidence that meningeal mast
cells can importantly contribute to the key features of stroke pathology,
including infiltration of granulocytes and activated macrophages, brain swelling,
and infarct size. We also obtained evidence that two mast cell-derived products,
interleukin-6 and, to a lesser extent, chemokine (C-C motif) ligand 7, can
contribute to stroke pathology. These findings indicate a novel role for mast
cells in the meninges, the membranes that envelop the brain, as potential
gatekeepers for modulating brain inflammation and pathology after stroke.
PMID- 25134762
TI - Alkylphenol Activity against Candida spp. and Microsporum canis: A Focus on the
Antifungal Activity of Thymol, Eugenol and O-Methyl Derivatives.
AB - In recent years there has been an increasing search for new antifungal compounds
due to the side effects of conventional antifungal drugs and fungal resistance.
The aims of this study were to test in vitro the activity of thymol, eugenol,
estragole and anethole and some O-methyl-derivatives (methylthymol and
methyleugenol) against Candida spp. and Microsporum canis. The broth
microdilution method was used to determine the minimum inhibitory concentration
(MIC). The minimum fungicidal concentrations (MFC) for both Candida spp. and M.
canis were found by subculturing each fungal suspension on potato dextrose agar.
Thymol, methylthymol, eugenol, methyl-eugenol, anethole, estragole and
griseofulvin respectively, presented the following MIC values against M. canis:
4.8-9.7; 78-150; 39; 78-150; 78-150; 19-39 ug/mL and 0.006-2.5 mg/mL. The MFC
values for all compounds ranged from 9.7 to 31 ug/mL. Concerning Candida spp,
thymol, methylthymol, eugenol, methyleugenol, anethole, estragole and
amphotericin, respectively, showed the following MIC values: 39; 620-1250; 150
620; 310-620; 620; 620-1250 and 0.25-2.0 mg/mL. The MFC values varied from 78 to
2500 ug/mL. All tested compounds thus showed in vitro antifungal activity against
Candida spp. and M. canis. Therefore, further studies should be carried out to
confirm the usefulness of these alkylphenols in vivo.
PMID- 25134764
TI - A New C-3/C-3"-Biflavanone from the Roots of Stellera chamaejasme L.
AB - A new 3, 3"-biflavanone, neochamaejasmin C (1), was isolated from the roots of
Stellera chamaejasme L., together with four known compounds. Their structures and
configurations were elucidated by spectroscopic methods, including 2D-NMR
techniques.
PMID- 25134765
TI - Quantitative Structure Inter-Activity Relationship (QSInAR). Cytotoxicity Study
of Some Hemisynthetic and Isolated Natural Steroids and Precursors on Human
Fibrosarcoma Cells HT1080.
AB - Combined experimental and quantitative structure inter-activity relationship
(QSIAR) computation methods were advanced in order to establish the structural
and mechanistic influences that steroids and triterpenes, either as newly
synthesized or naturally isolated products, have on human HT1080 mammalian cancer
cells. The main Hansch structural indicators such as hydrophobicity (LogP),
polarizability (POL) and total energy (Etot) were considered and both the
structure-projected as well as globally computed correlations were reported;
while the inter-activity correlation of the global activity with those projected
on structural information was revealed as equal to the direct structural-activity
one for the trial sets of compounds, the prediction for the testing set of
molecules reported even superior performances respecting those characteristic for
the calibration set, validating therefore the present QSInAR models; accordingly,
it follows that the LogP carries the most part of the cytotoxic signal, while POL
has little influence on inhibiting tumor growth-A complementary behavior with
their earlier known influence on genotoxic carcinogenesis. Regarding the newly
hemisynthetic compounds it was found that stigmasta-4,22-dien-3-one is not
adapted for cell membrane diffusion; it is recommended that aminocinnamyl
chlorohydrate be further modified in order to acquire better steric influence,
while aminocinnamyl-2,3,4,6-O-tetraacetyl-alpha-D-glucopyranoside was identified
as being inhibited in the tumor cell by other molecular mechanisms-here not
revealed-although it has a moderate-high anti-cancer structurally predicted
activity.
PMID- 25134766
TI - Metabolism study of notoginsenoside R1, ginsenoside Rg1 and ginsenoside Rb1 of
radix Panax notoginseng in zebrafish.
AB - Zebrafish, a common model organism for studies of vertebrate development and gene
function, has been used in pharmaceutical research as a new and powerful tool in
recent years. In the present study, we applied zebrafish for the first time in a
metabolic study of notoginsenoside (R1), ginsenoside (Rg1) and ginsenoside (Rb1),
which are saponins isolated from Panax notoginseng. Metabolites of these three
saponin compounds in zebrafish after exposure for 24 h were identified by high
performance liquid chromatography - electrospray mass spectrometry (HPLC-ESI-MS)
with a Zorbax C-18 column for separation using a binary gradient elution of 0.05%
formic acid acetonitrile - 0.05% formic acid water. The quasi-molecular ions of
compounds were detected in negative mode. Step-wise deglycosylation metabolites
and hydroxylation metabolites of the three saponins were found, which were
coincide with regular methods for metabolic analysis. Our study demonstrated that
the zebrafish model can successfully imitate the current metabolic model with
advantages of lower cost, far less amount of compound needed, easy set up and
high performance. Our data suggests that the zebrafish metabolic model has the
potential for developing a novel method for quickly predicting the metabolism of
Chinese herb components, including those of trace compounds.
PMID- 25134767
TI - Enzymatic synthesis of fatty hydroxamic acid derivatives based on palm kernel
oil.
AB - Fatty hydroxamic acid derivatives were synthesized using Lipozyme TL IM catalyst
at biphasic medium as the palm kernel oil was dissolved in hexane and
hydroxylamine derivatives were dissolved in water: (1) N-methyl fatty hydroxamic
acids (MFHAs); (2) N-isopropyl fatty hydroxamic acids (IPFHAs) and (3) N-benzyl
fatty hydroxamic acids (BFHAs) were synthesized by reaction of palm kernel oil
and N-methyl hydroxylamine (N-MHA), N-isopropyl hydroxylamine (N-IPHA) and N
benzyl hydroxylamine (N-BHA), respectively. Finally, after separation the
products were characterized by color testing, elemental analysis, FT-IR and 1H
NMR spectroscopy. For achieving the highest conversion percentage of product the
optimum molar ratio of reactants was obtained by changing the ratio of reactants
while other reaction parameters were kept constant. For synthesis of MFHAs the
optimum mol ratio of N-MHA/palm kernel oil = 6/1 and the highest conversion was
77.8%, for synthesis of IPFHAs the optimum mol ratio of N-IPHA/palm kernel oil =
7/1 and the highest conversion was 65.4% and for synthesis of BFHAs the optimum
mol ratio of N-BHA/palm kernel oil = 7/1 and the highest conversion was 61.7%.
PMID- 25134768
TI - Docking Studies and alpha-Substitution Effects on the Anti-Inflammatory Activity
of beta-Hydroxy-beta-arylpropanoic Acids.
AB - Six beta-hydroxy-beta-aryl propanoic acids were synthesised using a modification
of Reformatsky reaction which has already been reported. These acids belong to
the aryl propanoic acid class of compounds, structurally similar to the NSAIDs,
such as ibuprofen, and an anti-inflammatory activity is thus expected. The aim of
this work was to determine anti-inflammatory activity, examine gastric
tolerability, and to carry out molecular docking experiments to identify
potential COX-2 inhibitors among the beta-hydroxy-beta-aryl propanoic acids, and
to elucidate the effect alpha-methyl substitution on the anti-inflammatory
activity. Anti-inflammatory activity and gastric tolerability were determined on
rats using carrageenan induced paw oedema method, and docking studies were
carried out using Autodock v4.0.1. The range of ED50 values is between 127
umol/kg and 15 umol/kg, while the result for ibuprofen is 51.7 umol/kg. Only
slight hyperaemia or few petechiae were spotted on rat's stomach. The results
indicate that all compounds possess significant anti-inflammatory activity after
oral administration, and that 2-methyl-3-hydroxy-3,3-diphenyl-propanoic acid has
greatest activity, surpassing that of ibuprofen, a standard NSAID. Another
compound, 3-hydroxy-3,3-diphenylpropanoic acid, shows activity matching that of
ibuprofen, and is non-chiral and is proven to be non-toxic. The most of
investigated compounds have interactions with P3 anchor site like COX-2 selective
inhibitors. No tested substances or ibuprofen produced any significant gastric
lesions.
PMID- 25134769
TI - In Vitro Synergy of Biochanin A and Ciprofloxacin against Clinical Isolates of
Staphylococcus aureus.
AB - Many clinical isolates of Staphylococcus aureus (S. aureus) are resistant to
numerous antimicrobials, including the fluoroquinolones (FQs). Flavonoids such as
biochanin A (BCA) are compounds that are naturally present in fruits, vegetables,
and plant-derived beverages. The goal of this investigation was to study the
possible synergy between the antimicrobial agents BCA and ciprofloxacin (CPFX)
when used in combination; CPFX was chosen as a representative FQ compound. We
used S. aureus strain ATCC 25923 and 11 fluoroquinolone (FQ)-resistant
methicillin-resistant S. aureus (MRSA) strains. Results from the drug
susceptibility testing and checkerboard assays show that the minimum inhibitory
concentration (MIC) of BCA ranged from 64 ug/mL to 512 ug/mL. When BCA was
combined with CPFX, the fractional inhibitory concentration index (FICI) data
showed that there was synergy in all 12 of the S. aureus strains tested. No
antagonistic activity was observed in any of the strains tested. The results of
time-kill tests and agar diffusion tests confirm that there was synergy between
BCA and CPFX against S. aureus strains. These results suggest that BCA can be
combined with FQs to produce a powerful antimicrobial agent.
PMID- 25134770
TI - Green synthesis and antibacterial effect of silver nanoparticles using Vitex
negundo L.
AB - Different biological methods are gaining recognition for the production of silver
nanoparticles (Ag-NPs) due to their multiple applications. One of the most
important applications of Ag-NPs is their use as an anti-bacterial agent. The use
of plants in the synthesis of nanoparticles emerges as a cost effective and eco
friendly approach. In this study the biosynthesis of silver nanoparticles using
Vitex negundo L. extract and its antimicrobial properties has been reported. The
resulting silver particles are characterized using transmission electron
microscopy (TEM), X-ray diffraction (XRD) and UV-Visible (UV-Vis) spectroscopic
techniques. The TEM study showed the formation of silver nanoparticles in the 10
30 nm range and average 18.2 nm in size. The XRD study showed that the particles
are crystalline in nature, with a face centered cubic (fcc) structure. The silver
nanoparticles showed the antimicrobial activity against Gram positive and Gram
negative bacteria. Vitex negundo L. was found to display strong potential for the
synthesis of silver nanoparticles as antimicrobial agents by rapid reduction of
silver ions (Ag+ to Ag0).
PMID- 25134771
TI - Fast method for synthesis of alkyl and aryl-N-methylnitrones.
AB - A simple, fast, efficient and eco-friendly procedure was developed for the
synthesis of alkyl and aryl-N-methylnitrones. The corresponding nitrones of
aromatic aldehydes, aliphatic aldehydes and alicyclic carbonyl compounds were
prepared from N-methylhydroxylamine hydrochloride and Na2CO3-Na2SO4 by simply
grinding at room temperature without using solvent.
PMID- 25134772
TI - 3D-QSAR Study of Combretastatin A-4 Analogs Based on Molecular Docking.
AB - Combretastatin A-4 (CA-4), its analogues and their excellent antitumoral and
antivascular activities, have attracted considerable interest of medicinal
chemists. In this article, a docking simulation was used to identify molecules
having the same binding mode as the lead compound, and 3D-QSAR models had been
built by using CoMFA based on docking. As a result, these studies indicated that
the QSAR models were statistically significant with high predictabilities (CoMFA
model, q2 = 0.786, r2 = 0.988). Our models may offer help to better comprehend
the structure-activity relationships for this class of compounds and also
facilitate the design of novel inhibitors with good chemical diversity.
PMID- 25134775
TI - Cardanol-based materials as natural precursors for olefin metathesis.
AB - Cardanol is a renewable, low cost natural material, widely available as a by
product of the cashew industry. It is a mixture of 3-n-pentadecylphenol, 3
(pentadeca-8-enyl)phenol, 3-(pentadeca-8,11-dienyl)phenol and 3-(pentadeca
8,11,14-trienyl)phenol. Olefin metathesis (OM) reaction on cardanol is an
important class of reactions that allows for the synthesis of new olefins that
are sometime impossible to prepare via other methods. The application of this
natural and renewable material to both academic and industrial research will be
discussed.
PMID- 25134773
TI - Group 11 Metal Compounds with Tripodal Bis(imidazole) Thioether Ligands.
Applications as Catalysts in the Oxidation of Alkenes and as Antimicrobial
Agents.
AB - New group 11 metal complexes have been prepared using the previously described
tripodal bis(imidazole) thioether ligand (N-methyl-4,5-diphenyl-2
imidazolyl)2C(OMe)C(CH3)2S(tert-Bu) ({BITOMe,StBu}, 2). The pincer ligand offers
a N2S donor atom set that can be used to coordinate the group 11 metals in
different oxidation states [AuI, AuIII, AgI, CuI and CuII]. Thus the new
compounds [Au{BITOMe,StBu}Cl][AuCl4]2 (3), [Au{BITOMe,StBu}Cl] (4),
[Ag{BITOMe,StBu}X] (X = OSO2CF3- 5, PF6- 6) and [Cu{BITOMe,StBu}Cl2] (7) have
been synthesized from reaction of 2 with the appropriate metal precursors, and
characterized in solution. While attempting characterization in the solid state
of 3, single crystals of the neutral dinuclear mixed AuIII-AuI species
[Au2{BITOMe,S}Cl3] (8) were obtained and its crystal structure was determined by
X-ray diffraction studies. The structure shows a AuIII center coordinated to the
pincer ligand through one N and the S atom. The soft AuI center coordinates to
the ligand through the same S atom that has lost the tert-butyl group, thus
becoming a thiolate ligand. The short distance between the AuI-AuIII atoms (3.383
A) may indicate a weak metal-metal interaction. Complexes 2-7 and the previously
described CuI compound [Cu{BITOMe,StBu}]PF6 (9) have been evaluated in the
oxidation of biphenyl ethylene with tert-butyl hydrogen peroxide (TBHP) as the
oxidant. Results have shown that the AuI and AgI complexes 4 and 6 (at 10 mol %
loading) are the more active catalysts in this oxidative cleavage. The
antimicrobial activity of compounds 2-5, 7 and 9 against Gram-positive and Gram
negative bacteria and yeast has also been evaluated. The new gold and silver
compounds display moderate to high antibacterial activity, while the copper
derivatives are mostly inactive. The gold and silver complexes were also potent
against fungi. Their cytotoxic properties have been analyzed in vitro utilizing
HeLa human cervical carcinoma cells. The compounds displayed a very low
cytotoxicity on this cell line (5 to 10 times lower than cisplatin) and on normal
primary cells derived from C57B6 mouse muscle explants, which may make them
promising candidates as potential antimicrobial agents and safer catalysts due to
low toxicity in human and other mammalian tissues.
PMID- 25134776
TI - Essential Oil Composition of the Different Parts and In Vitro Shoot Culture of
Eryngium planum L.
AB - The essential oils obtained by hydrodistillation from the different parts
(inflorescence, stalk leaves, rosette leaves and root) as well as from in vitro
shoot culture of Eryngium planum L. were analyzed by GC-FID-MS in respect to
their chemical composition. The different parts of E. planum and in vitro shoots
showed different yields. The part with higher amount was the inflorescences,
followed by the stalk leaves and in vitro shoots, rosette leaves and finally
roots. The essential oils obtained from rosette leaves and in vitro-derived
rosettes had totally different composition. Quantitative differences were also
found between compounds of intact plant organs. The main components of stalk leaf
oil and rosette leaf oil were monoterpene (limonene, alpha- and beta-pinene) and
sesquiterpene hydrocarbons. In inflorescence oil cis-chrysanthenyl acetate
(43.2%) was accompanied by other esters (propionate, butanoate, hexanoate and
octanoate) and numerous oxygenated sesquiterpenes. Root oil and in vitro shoot
oil contained mainly (Z)-falcarinol and 2,3,4-trimethylbenzaldehyde. This is the
first report on the chemical composition of this species.
PMID- 25134774
TI - Proanthocyanidins from Grape Seeds Modulate the NF-kappaB Signal Transduction
Pathways in Rats with TNBS-Induced Ulcerative Colitis.
AB - To elucidate the molecular mechanisms involved in the therapeutic effects of
proanthocyanidins from grape seeds (GSPE), we explore whether GSPE regulates the
inflammatory response of TNBS-induced colitis in rats at the levels of NF-kappaB
signal transduction pathway. Rats were intragastrically administered of different
doses of GSPE (100, 200 and 400 mg.kg-1) per day for seven days after ulcerative
colitis (UC) was induced by intracolonic injection of 2,4,6
trinitrobenzenesulfonic acid (TNBS) dissolved in 50% ethanol. Sulfasalazine
(SASP) at 400 mg/kg was used as a positive control drug. The expression of
nuclear factor-kappa B (NF-kappaB), phospho-I kappaB-alpha (pIkappaBalpha),
inhibitor kappa B kinase (IkappaK) in the colon tissues were all measured by
enzyme-linked immunosorbent assay (ELISA) methods. Treatment with GSPE reduced
the expression of NF-kappaB, pIkappaBalpha and IkappaK in the colon. The results
of this study show that GSPE exerts beneficial effects in inflammatory bowel
disease by inhibition of NF-kappaB signal transduction pathways.
PMID- 25134777
TI - ESRD from autosomal dominant polycystic kidney disease in the United States, 2001
2010.
AB - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is amenable to
early detection and specialty care. Thus, while important to patients with the
condition, end-stage renal disease (ESRD) from ADPKD also may be an indicator of
the overall state of nephrology care. STUDY DESIGN: Retrospective cohort study of
temporal trends in ESRD from ADPKD and pre-renal replacement therapy (RRT)
nephrologist care, 2001-2010 (n = 23,772). SETTING & PARTICIPANTS: US patients
who initiated maintenance RRT from 2001 through 2010 (n = 1,069,343) from US
Renal Data System data. PREDICTOR: ESRD from ADPKD versus from other causes for
baseline characteristics and clinical outcomes; interval 2001-2005 versus 2006
2010 for comparisons of cohort of patients with ESRD from ADPKD. OUTCOMES: Death,
wait-listing for kidney transplant, kidney transplantation. MEASUREMENTS: US
census data were used as population denominators. Poisson distribution was used
to compute incidence rates (IRs). Incidence ratios were standardized to rates in
2001-2002 for age, sex, and race/ethnicity. Patients with and without ADPKD were
matched to compare clinical outcomes. Poisson regression was used to calculate
IRs and adjusted HRs for clinical events after inception of RRT. RESULTS: General
population incidence ratios in 2009-2010 were unchanged from 2001-2002 (incidence
ratio, 1.02). Of patients with ADPKD, 48.1% received more than 12 months of
nephrology care before RRT; preemptive transplantation was the initial RRT in
14.3% and fistula was the initial hemodialysis access in 35.8%. During 4.9 years
of follow-up, patients with ADPKD were more likely to be listed for
transplantation (IR, 11.7 [95% CI, 11.5-12.0] vs 8.4 [95% CI, 8.2-8.7] per 100
person-years) and to undergo transplantation (IR, 9.8 [95% CI, 9.5-10.0] vs 4.8
[95% CI, 4.7-5.0] per 100 person-years) and less likely to die (IR, 5.6 [95% CI,
5.4-5.7] vs 15.5 [95% CI, 15.3-15.8] per 100 person-years) than matched controls
without ADPKD. LIMITATIONS: Retrospective nonexperimental registry-based study of
associations; cause-and-effect relationships cannot be determined. CONCLUSIONS:
Although outcomes on dialysis therapy are better for patients with ADPKD than for
those without ADPKD, access to predialysis nephrology care and nondeclining ESRD
rates may be a cause for concern.
PMID- 25134778
TI - Risk factors for pregnancy outcomes in patients with IgA nephropathy: a matched
cohort study.
AB - BACKGROUND: The outcomes of pregnancy in immunoglobulin A nephropathy (IgAN) are
uncertain. This study assessed the effects of pregnancy on kidney disease
progression and risk factors for adverse pregnancy outcomes in IgAN. STUDY
DESIGN: A matched-cohort study. SETTING & PARTICIPANTS: Women with IgAN with at
least one pregnancy, 1 year of follow-up, and kidney function and proteinuria
measurement at baseline (time of biopsy) matched with nonpregnant women with IgAN
from Peking University First Hospital. PREDICTORS: Pregnancy, treated as a time
dependent variable; proteinuria; hypertension; and estimated glomerular
filtration rate (eGFR). OUTCOMES: Kidney disease progression, defined as eGFR
halving or end-stage kidney disease; rate of eGFR decline; and adverse pregnancy
outcomes, including severe pre-eclampsia, intrauterine death, embryo damage,
fetal malformation, and induced and spontaneous abortions. RESULTS: Of 239 female
patients, 62 women had 69 pregnancies and 62 matched nonpregnant patients were
selected as controls. Pregnant patients had median proteinuria at baseline with
protein excretion of 1.27 (range, 0.06-7.25)g/d and mean eGFR of 102.3 (range,
40.0-139.0)mL/min/1.73m(2). During a mean follow-up of 45.7 months, 4 patients in
the pregnancy group and 6 in the nonpregnancy group had kidney disease
progression events. Time-dependent Cox analysis showed that pregnancy was not an
independent risk factor for kidney disease progression events (HR, 1.2; 95%CI,
0.3-5.7). There was no significant difference in the median rate of eGFR decline
in the 2 groups (-2.5 vs -2.4mL/min/1.73m(2) per year; P=0.7). Adverse pregnancy
outcomes were observed in 15 patients. Proteinuria during pregnancy (OR, 1.39;
95%CI, 0.96-2.01) was a borderline predictor of adverse pregnancy outcomes.
LIMITATIONS: Retrospective study, most patients had preserved kidney function,
study underpowered to detect a difference in kidney failure events. CONCLUSIONS:
The study does not permit a definitive conclusion about the effect of pregnancy
on kidney disease progression in IgAN.
PMID- 25134779
TI - Acute physical activity and delayed attention in primary school students.
AB - To examine the influence of different types of exertion on immediate and delayed
attention in 116 primary school children divided in three groups of exertion
[cognitive exertion - CE (school curricular lesson), physical exertion - PE
(traditional physical education lesson), mixed cognitive and physical exertion -
CPE (coordinative physical education lesson)]. CPE was the combination of
physical load due to the practice of physical exercises and of cognitive load
requested to perform movement-based problem solving tasks requiring accurate
timing, temporal estimations, temporal production, and spatial adjustments.
Children's attentional capacity was tested before (pre) and after (at 0 min and
at 50 min post) a CE, a PE, or a CPE lesson, using the d2-test of attention, and
analyzed using a 3 * 3 * 2 mixed analysis of covariance with exertion type and
time as within factors, gender as between factor, and baseline data as covariate.
Effect sizes were calculated as partial eta squared (n(2)). Results showed that
participants' attentional performance was significantly affected by exertion type
(P < 0.0001), by time (P < 0.0001) and by exertion type * time interactions (P <
0.0001). The effect sizes ranged from medium (0.039) to large (0.437). Varying
the type of exertion has different beneficial influences on the level of
attention in school children.
PMID- 25134780
TI - Where and how to search for information on the effectiveness of public health
interventions--a case study for prevention of cardiovascular disease.
AB - BACKGROUND: This case study documents the experience of searching for information
on the effectiveness of population-level multi-factor interventions for the
prevention of cardiovascular disease (CVD) to inform guidance from NICE (National
Institute for Health and Care Excellence). OBJECTIVES: To compare suitability of
different databases for searches on a medical public health topic and performance
of sensitive versus specific strategies. METHODS: A sensitive search strategy
identified 34 CVD programmes (reference standard) and sensitivity, precision and
number needed to read (NNTR) were compared across seven databases. Two
alternative strategies were developed to improve precision while minimising the
impact on sensitivity. RESULTS: MEDLINE alone retrieved 91% (31/34) relevant
programme citations. Four databases (MEDLINE, CENTRAL, ASSIA and PsycINFO) were
required to identify all 34 programmes. In the alternative strategies, greater
use of MeSH rather than text and focus on terms directed at population-level
interventions resulted in a more precise search on MEDLINE. CONCLUSIONS: MEDLINE
alone provided a better yield than anticipated. Additional databases improved
sensitivity by 9% but to the detriment of precision. Retrospective searching
would provide additional insight into the performance of both databases and
strategies. How the medical nature of this public health topic affected yield
across databases also requires further investigation.
PMID- 25134782
TI - Rs37972 and rs37973 single-nucleotide polymorphisms in the glucocorticoid
inducible 1 gene are not associated with asthma risk in a Saudi Arabian
population.
AB - OBJECTIVE: Rs37972 and rs37973 variants in the glucocorticoid-induced transcript
1 gene have been associated with inhaled glucocorticosteroid responsiveness in
asthmatics; however, some discrepancies have been also reported. This study aims
to determine whether rs37972 and rs37973 SNPs are associated with asthma risk in
Saudi Arabian asthmatics. METHODS: Two-hundred seventy-one diagnosed asthmatics
(3-65 years old) and 387 healthy control subjects of equivalent age were
recruited. DNA from peripheral blood was purified, and genotyping of rs37972 and
rs37973 SNPs was performed by PCR amplification of segments of interest, followed
by Sanger sequencing. RESULTS: The global frequencies of the minor (risk) alleles
were 28% ("T" allele, rs37972) and 30% ("G" allele, rs37973). Yates-corrected Chi
square (chi(2)) tests revealed significant differences between asthmatic and
healthy groups, in allele frequencies for rs37973 SNP only (chi(2) = 3.98, Yates'
p value = 0.046). Regarding genotype frequencies, a significant difference
between asthmatic and healthy groups was observed for variant rs37972 only
(chi(2) = 8.19, Yates' p value = 0.016). To determine a possible association of
the minor "T" and "G" alleles with asthma, both the recessive and dominant
genetic models were tested. For rs37973, none of the genotypes were significantly
associated with asthma. Concerning rs37972, the dominant model (C/T + T/T versus
C/C) indicated a significant "protective" association with asthma, in which C/T +
T/T individuals had lower odds of being asthmatics than C/C individuals (OR =
0.67; 95% CI = 0.48-0.94; p = 0.019*). CONCLUSIONS: The minor alleles "T" and "G"
of rs37972 and rs37973 SNPs, respectively, were not significantly associated with
increased asthma risk in asthma patients from Saudi Arabia.
PMID- 25134781
TI - Associations between central obesity and asthma in children and adolescents: a
case-control study.
AB - INTRODUCTION: Evidence supports a significant yet weak association between high
body weight and asthma in children. However, most studies investigating the
obesity-asthma link use Body Mass Index (BMI) to evaluate body fatness. The
relationship between body fat distribution and asthma remains largely unknown,
especially in children. This pediatric case-control investigation examined
associations between central obesity/high-body weight and asthma diagnosis.
METHODS: Five-hundred and fourteen children (217 physician diagnosed asthma cases
and 297 healthy controls) of 5-11 years were recruited. Height, weight and waist
circumference were measured. Asthma symptoms, past medical history, personal
lifestyle, socioeconomic status, diet and physical activity history were also
collected. RESULTS: A higher proportion of children with asthma were centrally
obese [(>=90th waist percentile) 15.2 vs. 9.4%, p<0.0001; (>=90th waist-to-height
ratio percentile) 39.6 vs. 24.2%, p<0.0001)]. Regression analyses revealed that
centrally obese children were more likely to have asthma (high-waist
circumference (OR = 1.99, 95% CI: 1.07-3.68) and high-waist circumference to
height ratio (OR = 2.24, 95% CI: 1.47-3.40), following adjustment for various
confounders. Overweight/obese participants (BMI defined) were more likely to be
asthmatic [odds ratio (OR) = 1.52, 95% confidence interval (CI): 1.03-2.70)] when
compared to controls. CONCLUSIONS: Presence of central obesity and high-body
weight (at least overweight) as assessed by waist circumference, waist-to-height
ratio, and BMI are associated with asthma diagnosis. More studies are needed,
especially in children and adolescents, to confirm these findings and better
understand how body fat distribution impacts the obesity-asthma relationship.
PMID- 25134784
TI - A nested case-control study: personal, social and environmental correlates of
vigorous physical activity in adolescents with asthma.
AB - OBJECTIVE: Physical activity (PA) is associated with health benefits. Children
and adolescents with asthma may be limited in their PA, particularly at vigorous
intensity due to asthma symptoms or poor psychological adjustment to asthma. We
aimed to investigate if self-perceived competence, enjoyment, support from others
and social-physical environment were associated with vigorous physical activity
(VPA) and secondarily to assess if such associations were modified by asthma and
asthma severity. METHODS: Data from a nested case-control study at 13 years of
age within the birth-cohort Environment and Childhood Asthma Study were compiled
from 95 participants with and 79 without asthma. The participants completed a
questionnaire designed to capture self-perceived competence, enjoyment, support
from others and social-physical environment. VPA, defined as >= 6 Metabolic
Equivalents, was recorded objectively by SenseWearTM Pro2 Armband. Asthma
severity was assessed pragmatically by lung function and use of inhaled
glucocorticosteroids and beta2-agonists and incidence of exacerbations in the
last 14 days. Data were analysed using linear regression analysis. RESULTS: No
significant differences between adolescents with and without asthma were
identified in terms of VPA, competence-enjoyment, support from others and social
physical environment. Peer support (b = 0.29 (0.05-0.52)) and competence
enjoyment (b = 0.23 (0.01-0.44)) were significantly and positively associated
with VPA, and teacher support (b = -0.26 (-0.50 to -0.02)) were inversely
associated. The model explained 25% of the variance in VPA. CONCLUSIONS: Peer
support and competence-enjoyment were positively associated with increased VPN in
adolescents irrespectively of asthma and asthma severity.
PMID- 25134783
TI - Spirometry effects on conventional and multiple flow exhaled nitric oxide in
children.
AB - OBJECTIVE: Clinical and research settings often require sequencing multiple
respiratory tests in a brief visit. Guidelines recommend measuring the
concentration of exhaled nitric oxide (FeNO) before spirometry, but evidence for
a spirometry carryover effect on FeNO is mixed. Only one study has investigated
spirometry carryover effects on multiple flow FeNO analysis. The objective of
this study was to evaluate evidence for carryover effects of recent spirometry on
three exhaled NO summary measures: FeNO at 50 ml/s, airway wall NO flux [J'awNO]
and alveolar NO concentration [CANO] in a population-based sample of
schoolchildren. METHODS: Participants were 1146 children (191 with asthma), ages
12-15, from the Southern California Children's Health Study who performed
spirometry and multiple flow FeNO on the same day. Approximately, half the
children performed spirometry first. Multiple linear regression was used to
estimate differences in exhaled NO summary measures associated with recent
spirometry testing, adjusting for potential confounders. RESULTS: In the
population-based sample, we found no evidence of spirometry carryover effects.
However, for children with asthma, there was a suggestion that exhaled NO summary
measures assessed <=6 min after spirometry were lower (FeNO: 25.8% lower, 95% CI:
-6.2%, 48.2%; J'awNO: 15.1% lower 95% CI: -26.5%, 43.0%; and CANO 0.43 parts per
billion lower, 95% CI: -0.12, 0.98). CONCLUSIONS: In clinical settings, it is
prudent to assess multiple flow FeNO before spirometry. In studies of healthy
subjects, it may not be necessary to assess FeNO first.
PMID- 25134785
TI - Maternal psychological distress mediates the relationship between asthma and
physician visits in a population-based sample of adolescents.
AB - OBJECTIVE: This study examined whether maternal psychological distress mediates
the relationship between presence of adolescent asthma and number of physician
visits and whether the association between maternal psychological distress and
physician visits is moderated by adolescent general health. METHODS: Data were
obtained from the Mater University Study of Pregnancy and included 4025
adolescents. Path analysis was used to examine mediating and moderating effects.
RESULTS: Maternal psychological distress was found to partially mediate the
relationship between adolescent asthma and number of physician visits, accounting
for 25% of the effect of adolescent asthma on physician visits (p = 0.046). There
was no evidence to suggest that adolescent general health moderated the
association between maternal psychological distress and physician visits (p =
0.093). CONCLUSIONS: These findings suggest that maternal psychological distress
is associated with increased physician visits, regardless of adolescents' general
health. Lowering maternal psychological distress may serve to reduce health care
utilization and costs among adolescents with asthma.
PMID- 25134786
TI - Characteristics of postural control among young adults with asthma.
AB - OBJECTIVE: We investigated whether young adults with asthma have impaired balance
and whether this impairment is related to altered musculoskeletal function and/or
psychological characteristics. METHODS: 21 participants with a self-reported
asthma diagnosis but no known postural instability or history of falls, and 18
control participants were recruited from undergraduate psychology courses.
Participants performed a postural control task of maintaining the center of
pressure (COP) in a fixed position with visual feedback (feedback condition) and
while standing as still as possible without visual feedback (no-feedback
condition). COP variability, regularity and task performance were used to
characterize the quality of balance. To document group differences in
musculoskeletal function, we measured neck and lower back angles as well as range
of motion (ROM) of the neck in the frontal and sagittal planes. To document group
differences in psychological state, we administered self-report questionnaires to
assess symptoms of anxiety and depression, anxiety sensitivity and negative
effect. RESULTS: COP variability and task performance were similar between the
groups, but participants with asthma exhibited more regular anterior-posterior
COP dynamics. Participants with asthma had smaller ROM of neck extension, a more
forwardly bent neck, greater thoracic spine angle, and they reported greater
levels of the physical concerns facet of anxiety sensitivity. These
musculoskeletal and affective variables moderated COP differences between the
groups. CONCLUSIONS: Young adults with asthma showed a different postural control
strategy in the absence of any obvious balance impairment. This change in
strategy is related to musculoskeletal and affective characteristics of
individuals with asthma.
PMID- 25134788
TI - Vitamin D counteracts fibrogenic TGF-beta signalling in human hepatic stellate
cells both receptor-dependently and independently.
AB - OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is closely linked to obesity
and constitutes part of the metabolic syndrome, which have been associated with
low serum vitamin D (VD). Due to known crosstalk between VD and transforming
growth factor (TGF)-beta signalling, VD has been proposed as an antifibrotic
treatment. DESIGN: We evaluated the association between VD, the vitamin D
receptor (VDR) and liver fibrosis in primary human hepatic stellate cells (phHSC)
and 106 morbidly obese patients with NAFLD. RESULTS: Treating phHSC with VD
ameliorated TGF-beta-induced fibrogenesis via both VDR-dependent and VDR
independent mechanisms. Reduction of fibrogenic response was abolished in cells
homozygous for GG at the A1012G single nucleotide polymorphisms within the VDR
gene. Compared with healthy livers, NAFLD livers expressed higher levels of VDR
mRNA and VDR fragments. VDR mRNA was lower in patients homozygous for GG at
A1012G and expression of pro-fibrogenic genes was higher in patients carrying the
G allele. CONCLUSIONS: VD may be an antifibrotic treatment option early in the
onset of fibrosis in specific genotypes for VDR. Known polymorphisms of the VDR
may influence the response to VD treatment.
PMID- 25134789
TI - Regression analysis of correlated ordinal data using orthogonalized residuals.
AB - Semi-parametric regression models for the joint estimation of marginal mean and
within-cluster pairwise association parameters are used in a variety of settings
for population-averaged modeling of multivariate categorical outcomes. Recently,
a formulation of alternating logistic regressions based on orthogonalized,
marginal residuals has been introduced for correlated binary data. Unlike the
original procedure based on conditional residuals, its covariance estimator is
invariant to the ordering of observations within clusters. In this article, the
orthogonalized residuals method is extended to model correlated ordinal data with
a global odds ratio, and shown in a simulation study to be more efficient and
less biased with regards to estimating within-cluster association parameters than
an existing extension to ordinal data of alternating logistic regressions based
on conditional residuals. Orthogonalized residuals are used to estimate a model
for three correlated ordinal outcomes measured repeatedly in a longitudinal
clinical trial of an intervention to improve recovery of patients' perception of
altered sensation following jaw surgery.
PMID- 25134791
TI - Swahili speech development: preliminary normative data from typically developing
pre-school children in Tanzania.
AB - BACKGROUND: Swahili is widely spoken in East Africa, but to date there are no
culturally and linguistically appropriate materials available for speech-language
therapists working in the region. The challenges are further exacerbated by the
limited research available on the typical acquisition of Swahili phonology. AIM:
To describe the speech development of 24 typically developing first language
Swahili-speaking children between the ages of 3;0 and 5;11 years in Dar es
Salaam, Tanzania. METHODS & PROCEDURES: A cross-sectional design was used with
six groups of four children in 6-month age bands. Single-word speech samples were
obtained from each child using a set of culturally appropriate pictures designed
to elicit all consonants and vowels of Swahili. Each child's speech was audio
recorded and phonetically transcribed using International Phonetic Alphabet (IPA)
conventions. Children's speech development is described in terms of (1) phonetic
inventory, (2) syllable structure inventory, (3) phonological processes and (4)
percentage consonants correct (PCC) and percentage vowels correct (PVC). RESULTS
& OUTCOMES: Results suggest a gradual progression in the acquisition of speech
sounds and syllables between the ages of 3;0 and 5;11 years. Vowel acquisition
was completed and most of the consonants acquired by age 3;0. Fricatives/z, s, h/
were later acquired at 4 years and /theta/and /r/ were the last acquired
consonants at age 5;11. Older children were able to produce speech sounds more
accurately and had fewer phonological processes in their speech than younger
children. Common phonological processes included lateralization and sound
preference substitutions. CONCLUSIONS & IMPLICATIONS: The study contributes a
preliminary set of normative data on speech development of Swahili-speaking
children. Findings are discussed in relation to theories of phonological
development, and may be used as a basis for further normative studies with larger
numbers of children and ultimately the development of a contextually relevant
assessment of the phonology of Swahili-speaking children.
PMID- 25134792
TI - 13C-engineered carbon quantum dots for in vivo magnetic resonance and
fluorescence dual-response.
AB - (13)C-engineered carbon quantum dots ((13)C-QDs) were used as magnetic resonance
(MR) and fluorescence dual-response probe. The enhanced (13)C-MR signal was
observed at 171 ppm from carboxylic and carboxyl carbons in (13)C-QDs with 160
fold improvement on signal-to-noise ratio even when no hyperpolarization was
applied, whereas the intrinsic fluorescence of C-QDs was still maintained. The
stable MR and fluorescence dual-response was successfully used for long-term
observation of zebrafish embryonic development. Cross-validation between MR and
fluorescence confirmed the distribution of (13)C-QD in zebrafish. (13)C-MR
provides specific information about the presence, magnitude, and progression of
(13)C-QDs by defining MR intensity, whereas fluorescence reveals the location of
(13)C-QDs with its high sensitivity. (13)C-MR and fluorescence was simultaneously
observed within (13)C-QDs, and this work may expand the applications of isotope
engineered nanomaterials.
PMID- 25134787
TI - A pro-inflammatory role for Th22 cells in Helicobacter pylori-associated
gastritis.
AB - OBJECTIVE: Helper T (Th) cell responses are critical for the pathogenesis of
Helicobacter pylori-induced gastritis. Th22 cells represent a newly discovered Th
cell subset, but their relevance to H. pylori-induced gastritis is unknown.
DESIGN: Flow cytometry, real-time PCR and ELISA analyses were performed to
examine cell, protein and transcript levels in gastric samples from patients and
mice infected with H. pylori. Gastric tissues from interleukin (IL)-22-deficient
and wild-type (control) mice were also examined. Tissue inflammation was
determined for pro-inflammatory cell infiltration and pro-inflammatory protein
production. Gastric epithelial cells and myeloid-derived suppressor cells (MDSC)
were isolated, stimulated and/or cultured for Th22 cell function assays. RESULTS:
Th22 cells accumulated in gastric mucosa of both patients and mice infected with
H. pylori. Th22 cell polarisation was promoted via the production of IL-23 by
dendritic cells (DC) during H. pylori infection, and resulted in increased
inflammation within the gastric mucosa. This inflammation was characterised by
the CXCR2-dependent influx of MDSCs, whose migration was induced via the IL-22
dependent production of CXCL2 by gastric epithelial cells. Under the influence of
IL-22, MDSCs, in turn, produced pro-inflammatory proteins, such as S100A8 and
S100A9, and suppressed Th1 cell responses, thereby contributing to the
development of H. pylori-associated gastritis. CONCLUSIONS: This study,
therefore, identifies a novel regulatory network involving H. pylori, DCs, Th22
cells, gastric epithelial cells and MDSCs, which collectively exert a pro
inflammatory effect within the gastric microenvironment. Efforts to inhibit this
Th22-dependent pathway may therefore prove a valuable strategy in the therapy of
H. pylori-associated gastritis.
PMID- 25134794
TI - A case of acute glutaraldehyde-induced colitis following polyps treated by EMR.
PMID- 25134793
TI - Second harmonic generation microscopy analysis of extracellular matrix changes in
human idiopathic pulmonary fibrosis.
AB - Patients with idiopathic fibrosis (IPF) have poor long-term survival as there are
limited diagnostic/prognostic tools or successful therapies. Remodeling of the
extracellular matrix (ECM) has been implicated in IPF progression; however, the
structural consequences on the collagen architecture have not received
considerable attention. Here, we demonstrate that second harmonic generation
(SHG) and multiphoton fluorescence microscopy can quantitatively differentiate
normal and IPF human tissues. For SHG analysis, we developed a classifier based
on wavelet transforms, principle component analysis, and a K-nearest-neighbor
algorithm to classify the specific alterations of the collagen structure observed
in IPF tissues. The resulting ROC curves obtained by varying the numbers of
principal components and nearest neighbors yielded accuracies of >95%. In
contrast, simpler metrics based on SHG intensity and collagen coverage in the
image provided little or no discrimination. We also characterized the change in
the elastin/collagen balance by simultaneously measuring the elastin
autofluorescence and SHG intensities and found that the IPF tissues were less
elastic relative to collagen. This is consistent with known mechanical
consequences of the disease. Understanding ECM remodeling in IPF via nonlinear
optical microscopy may enhance our ability to differentiate patients with rapid
and slow progression and, thus, provide better prognostic information.
PMID- 25134795
TI - Polycomb protein EED is required for silencing of pluripotency genes upon ESC
differentiation.
AB - Eed (embryonic ectoderm development) is a core component of the Polycomb
Repressive Complex 2 (PRC2) which catalyzes the methylation of histone H3 lysine
27 (H3K27). Trimethylated H3K27 (H3K27me3) can act as a signal for PRC1
recruitment in the process of gene silencing and chromatin condensation. Previous
studies with Eed KO ESCs revealed a failure to down-regulate a limited list of
pluripotency factors in differentiating ESCs. Our aim was to analyze the
consequences of Eed KO for ESC differentiation. To this end we first analyzed ESC
differentiation in the absence of Eed and employed in silico data to assess
pluripotency gene expression and H3K27me3 patterns. We linked these data to
expression analyses of wildtype and Eed KO ESCs. We observed that in wildtype
ESCs a subset of pluripotency genes including Oct4, Nanog, Sox2 and Oct4 target
genes progressively gain H3K27me3 during differentiation. These genes remain
expressed in differentiating Eed KO ESCs. This suggests that the deregulation of
a limited set of pluripotency factors impedes ESC differentiation. Global
analyses of H3K27me3 and Oct4 ChIP-seq data indicate that in ESCs the binding of
Oct4 to promoter regions is not a general predictor for PRC2-mediated silencing
during differentiation. However, motif analyses suggest a binding of Oct4
together with Sox2 and Nanog at promoters of genes that are PRC2-dependently
silenced during differentiation. In summary, our data further characterize Eed
function in ESCs by showing that Eed/PRC2 is essential for the onset of ESC
differentiation.
PMID- 25134796
TI - Generation of intermediate porcine iPS cells under culture condition favorable
for mesenchymal-to-epithelial transition.
AB - It has been demonstrated that naive and primed pluripotency are determined by
different extracellular signals. In this study, we investigated whether
intermediate pluripotent states could be available by manipulating the culture
condition during the process of generating pig induced pluripotent stem cells
(piPSCs). By optimizing the culture condition that efficiently promotes
mesenchymal-to-epithelial transition (MET), we found that combination of three
growth factors (LIF, FGF2 and BMP4) and two inhibitors (2i: CHIR99021 and
SB431542) could generate an intermediate pluripotent state of piPSCs, which were
named as LFB2i-piPSCs. The LFB2i-piPSCs are stable and fulfill all the criteria
of pluripotency, including expression of pluripotent genes, differentiation into
three germ layers via embryoid bodies in vitro and teratoma in vivo. More
importantly, the mRNA-sequencing data showed that LFB2i-piPSCs had a mixed
transcriptome of naive and primed pluripotency, which featured by expressing high
levels of SOX2, L-MYC and ESRRB and relatively low levels of POU5F1, KLF4 and
NANOG. Small RNA sequencing also demonstrated that LFB2i-piPSCs had a mixed
microRNA profile of naive and primed pluripotency, which featured by expressing
high levels of miR-302b/367 cluster and miR-106a/363 cluster, and low levels of
most let-7 family members and miR-17/92 cluster. Altogether, the LFB2i-piPSCs
represent a stable intermediate pluripotent state with unique transcriptome and
microRNA signatures. The LFB2i-piPSCs will provide a new tool to explore the
mechanisms of pluripotency and reprogramming on pig species.
PMID- 25134798
TI - Low prospects and high risk: structural determinants of health associated with
sexual risk among young African American women residing in resource-poor
communities in the south.
AB - African American women at increased risk of HIV/sexually transmitted infection
(STI) may engage in risky sex as a coping mechanism for depressed economic
conditions. This study examines the association between high-risk sexual behavior
and structural determinants of sexual health among a sample of young African
American women. 237 young African American women (16-19 years old) from
economically disadvantaged neighborhoods in North Carolina were enrolled into a
randomized trial testing the efficacy of an adapted HIV/STI prevention
intervention. Logistic regression analyses predicted the likelihood that young
women reporting lack of food at home, homelessness and low future prospects would
also report sexual risk behaviors. Young women reporting a lack of food at home
(22 %), homelessness (27 %), and low perceived education/employment prospects (19
%) had between 2.2 and 4.7 times the odds as those not reporting these risk
factors of reporting multiple sex partners, risky sex partners including older
men and partners involved in gangs, substance use prior to sex, and exchange sex.
Self-reported structural determinants of sexual health were associated with
myriad sexual risk behaviors. Diminished economic conditions among these young
women may lead to sexual risk due to hopelessness, the need for survival or other
factors.
PMID- 25134797
TI - Construction of corneal epithelium with human amniotic epithelial cells and
repair of limbal deficiency in rabbit models.
AB - This study aims to evaluate the effect of a human amniotic epithelial cell (HAEC)
rabbit corneal stroma tissue-engineered cornea on ocular reconstruction in three
different animal models. HAECs were isolated from human placenta, seeded onto
rabbit corneal stroma. HAECs-rabbit corneal stroma tissue engineering cornea
transplantation was examined in three distinct rabbit models: transplantation of
cornea constructed (1) with lamellar corneal HAECs and rabbit corneal stroma, (2)
with central corneal HAECs and rabbit corneal stroma, or (3) with full-thickness
corneal HAECs and rabbit corneal stroma. In the tissue engineering corneal
transplantation groups in all three models, the mean number of days to corneal
epithelial healing was significantly shorter than that in the control group and
the mean number of days to corneal neovascularization was significantly greater
than in the control group. In addition, in the tissue engineering corneal
transplantation groups in the central lamellar cornea model and the full
thickness corneal transplantation model neovascularization, corneal turbidity,
and epithelial fluorescence were significantly less than in the control groups.
HAECs can be induced to differentiate into corneal epithelial cells, which may be
suitable for the reconstruction of the corneal epithelium in cases of limbal stem
cell deficiency.
PMID- 25134801
TI - Evaluation of (68)Ga-DOTANOC PET/CT imaging in a large exclusive population of
pancreatic neuroendocrine tumors.
AB - PURPOSE: To evaluate the diagnostic accuracy of (68)Ga-DOTANOC PET/CT imaging in
a large exclusive population of pancreatic neuroendocrine tumors (NETs). METHODS:
Data of 141 (mean age 46.2 +/- 15.2 years) patients who underwent 178 (68)Ga
DOTANOC PET/CT studies for diagnosis/staging (n = 88) and restaging (n = 90) of
pancreatic NET were retrospectively analyzed. PET/CT results were compared to
conventional imaging (CIM) when available (n = 86). Histopathology and/or
clinical/imaging follow-up (minimum 6 months) were used as reference standard.
RESULTS: The overall sensitivity, specificity, and accuracy of (68)Ga-DOTANOC
PET/CT were 85.7%, 79.1%, and 84.8%. The corresponding values were 73%, 50%, and
70.4% for diagnosis/staging groups and 98.6%, 100%, and 98.8% for restaging
groups. The accuracy was significantly higher for restaging as compared to
diagnosis/staging (P < 0.0001) and in non-insulinoma tumors than insulinomas (P <
0.0001). The SUVmax of primary tumors was significantly higher than metastatic
lesions overall (P = 0.001), as well as in diagnosis/staging (P = 0.041) and
restaging (P = 0.0003) subgroups. When available, CIM was less specific than
(68)Ga-DOTANOC PET/CT (P < 0.001) and showed fewer lesions. CONCLUSIONS: (68)Ga
DOTANOC PET/CT is useful for diagnosis/staging and restaging of patients with
pancreatic NET. It demonstrates more lesions compared to CIM and is more
specific.
PMID- 25134799
TI - The roles of troponin C isoforms in the mechanical function of Drosophila
indirect flight muscle.
AB - Stretch activation (SA) is a fundamental property of all muscle types that
increases power output and efficiency, yet its mechanism is unknown. Recently,
studies have implicated troponin isoforms as important in the SA mechanism. The
highly stretch-activated Drosophila IFMs express two isoforms of the Ca(2+)
binding subunit of troponin (TnC). TnC1 (TnC-F2 in Lethocerus IFM) has two
calcium binding sites, while an unusual isoform, TnC4 (TnC-F1 in Lethocerus IFM),
has only one binding site. We investigated the roles of these two TnC isoforms in
Drosophila IFM by targeting RNAi to each isoform. IFMs with TnC4 expression
(normally ~90% of total TnC) replaced by TnC1 did not generate isometric tension,
power or display SA. However, TnC4 knockdown resulted in sarcomere ultrastructure
disarray, which could explain the lack of mechanical function and thus make
interpretation of the influence of TnC4 on SA difficult. Elimination of TnC1
expression (normally ~10% of total TnC) by RNAi resulted in normal muscle
structure. In these IFMs, fiber power generation, isometric tension, stretch
activated force and calcium sensitivity were statistically identical to wild
type. When TnC1 RNAi was driven by an IFM specific driver, there was no decrease
in flight ability or wing beat frequency, which supports our mechanical findings
suggesting that TnC1 is not essential for the mechanical function of Drosophila
IFM. This finding contrasts with previous work in Lethocerus IFM showing TnC1 is
essential for maximum isometric force generation. We propose that differences in
TnC1 function in Lethocerus and Drosophila contribute to the ~40-fold difference
in IFM isometric tension generated between these species.
PMID- 25134800
TI - Relationship of bone mineralization density distribution (BMDD) in cortical and
cancellous bone within the iliac crest of healthy premenopausal women.
AB - Bone mineralization density distribution (BMDD) is an important determinant of
bone mechanical properties. The most available skeletal site for access to the
BMDD is the iliac crest. Compared to cancellous bone much less information on
BMDD is available for cortical bone. Hence, we analyzed complete transiliac crest
bone biopsy samples from premenopausal women (n = 73) aged 25-48 years,
clinically classified as healthy, by quantitative backscattered electron imaging
for cortical (Ct.) and cancellous (Cn.) BMDD. The Ct.BMDD was characterized by
the arithmetic mean of the BMDD of the cortical plates. We found correlations
between Ct. and Cn. BMDD variables with correlation coefficients r between 0.42
and 0.73 (all p < 0.001). Additionally to this synchronous behavior of cortical
and cancellous compartments, we found that the heterogeneity of mineralization
densities (Ct.Ca(Width)), as well as the cortical porosity (Ct.Po) was larger for
a lower average degree of mineralization (Ct.Ca(Mean)). Moreover, Ct.Po
correlated negatively with the percentage of highly mineralized bone areas
(Ct.Ca(High)) and positively with the percentage of lowly mineralized bone areas
(Ct.Ca(Low)). In conclusion, the correlation of cortical with cancellous BMDD in
the iliac crest of the study cohort suggests coordinated regulation of bone
turnover between both bone compartments. Only in a few cases, there was a
difference in the degree of mineralization of >1wt % between both cortices
suggesting a possible modeling situation. This normative dataset of healthy
premenopausal women will provide a reference standard by which disease- and
treatment-specific effects can be assessed at the level of cortical bone BMDD.
PMID- 25134802
TI - Radiological diagnosis and management of idiopathic spontaneous intra-abdominal
haemorrhage (abdominal apoplexy): a case series.
AB - PURPOSE: Idiopathic spontaneous intraperitoneal haemorrhage (ISIH), historically
known as abdominal apoplexy, is spontaneous haemorrhage due to rupture of an
intra-abdominal visceral vessel in the absence of trauma or underlying pathology.
It is an exceptionally rare condition, with mostly scattered case reports
available. The aim of this study was to describe this rare condition, possible
associated risk factors, and usefulness of multislice-CT (MS-CT) angiogram in its
diagnosis prior to intervention. METHODS: A retrospective review of patients
diagnosed with ISIH. Radiological records of haemoperitoneum from a single
tertiary hospital in 2006-2013 were analysed, and the cases of ISIH were
identified. Demographics (including pre-morbid hypertension status), abdominal
aortic calcification as a measure of atherosclerotic changes, MS-CT angiogram +/-
conventional digital subtraction angiograph images, surgical records and outcomes
were reviewed. RESULTS: 425 cases of haemoperitoneum were retrieved from hospital
radiology database from 2006 to 2013, and 5 patients (1.1%) diagnosed with ISIH
were identified (4 males, 1 female, mean age of 64 years). 4 out of 5 patients
(80%) had a history of hypertension (mean 150/90 mmHg) and 3 patients had
moderate abdominal aortic atherosclerosis. MS-CT angiogram was able to diagnose
the bleeding source in 4 out of 5 patients, while the bleeding source remained
occult in the last patient even with both MS-CT and traditional DSA angiography.
Patients who underwent either embolization or surgery had no further re-bleeding
in clinical follow up, ranging from 5 to 8 years. CONCLUSIONS: Hypertension and
abdominal aortic atherosclerosis appear to be associated risk factors for ISIH,
and MS-CT angiogram has a high sensitivity in detecting the site of haemorrhage.
An integrated angiographic and surgical approach is important in managing
patients with ISIH.
PMID- 25134803
TI - Does abdominal pain duration affect the accuracy of first-line MRI for pediatric
appendicitis?
AB - PURPOSE: To compare the accuracy of first-line MRI for pediatric appendicitis
between children with different durations of abdominal pain. MATERIALS AND
METHODS: Between November 2012 and September 2013, 364 pediatric patients
underwent MRI for clinically suspected appendicitis. Patients were stratified
into one group with pain lasting less than or equal to 1 day and pain longer than
1 day. RESULTS: In patients with early abdominal pain, appendicitis occurred in
83 of 208 patients (39.9%) vs. 49 of 156 patients with pain longer than 1 day
(31.4%, p = 0.09). Sensitivity and specificity of MRI in patients with early
abdominal pain were 97.6% (95% CI [91.6%-99.3%]) and 94.4% (95% CI [88.9%
97.3%]), respectively, vs. 93.9% (95% CI [83.5%-97.9%]) and 97.2% (95% CI [92.1%
99.4%]), respectively, in patients with pain longer than 1 day in duration (p =
0.36 and p = 0.35 for sensitivity and specificity, respectively). CONCLUSIONS:
First-line MRI is accurate for acute appendicitis in children presenting with
early abdominal pain, and may be appropriate as the initial examination in
children. Further prospective studies are needed to compare MRI vs. ultrasound as
the initial examination in children with early abdominal pain to help further
delineate a diagnostic imaging algorithm.
PMID- 25134804
TI - Gly322Asp and Asn127Ser single nucleotide polymorphisms (SNPs) of hMSH2 mismatch
repair gene and the risk of triple-negative breast cancer in Polish women.
AB - Triple-negative breast cancer (TNBC) is characterised by worse clinical outcome
and poor prognosis. The alterations in the oncogenes and tumor suppressor genes
as well as microsatellite instability (MSI) have been associated with breast
cancer development. It is knowledge that the most common mechanism inducing MSI
in many cancer is genomic rearrangements found in the hMSH2 (human MutS homolog
2) gene. In this report we genotyped two polymorphisms of hMSH2 DNA repair gene
in 70 TNBC patients and 70 age-matched cancer-free women using RFLP-PCR. The
following polymorphisms were studied: an A/G transition at 127 positions
producing an Asn/Ser substitution at codon 127 (the Asn127Ser polymorphism,
rs17217772) and a G/A transition at 1032 position resulting in a Gly/Asp change
at codon 322 (the Gly322Asp polymorphism, rs4987188). We found an association
between the hMSH2 Asp/Asp and Gly/Asp genotypes and TNBC occurence. Variant Asp
allele of hMSH2 decreased cancer risk [odds ratio (OR) 0.11; 95 % confidence
interval (CI) 0.05-0.21]. The risk of TNBC in the carriers of the Gly322Gly
Asn127Ser combined genotype was increased (OR 3.71; 95 % CI 1.36-10.10). However
the risk of TNBC was not alter by polymorphism Asn127Ser of the hMSH2 gene. The
Gly322Asp polymorphism of the hMSH2 gene may be linked with TNBC occurrence in
Polish women.
PMID- 25134805
TI - Genetic and demographic bottleneck analysis of Indian camel breeds by
microsatellite markers.
AB - The genetic and demographic bottleneck analysis of Indian camel breeds was
carried out utilizing 40 microsatellite markers. Allelic polymorphism was
observed at 20 loci in the Indian dromedary breeds. A total of 66 alleles were
scored. The average number of alleles, expected heterozygosity and polymorphic
information content were, respectively, 3.25 +/- 0.27, 0.56 +/- 0.04 and 0.49 +/-
0.04 in Bikaneri; 3.25 +/- 0.25, 0.53 +/- 0.03 and 0.46 +/- 0.03 in Jaisalmeri;
3.0 +/- 0.21, 0.53 +/- 0.04 and 0.45 +/- 0.03 in Kachchhi and 3.1 +/- 0.19, 0.51
+/- 0.03 and 0.44 +/- 0.03 in Mewari breed. Higher genetic variation was observed
in most numerous Bikaneri breed. Genetic distances were least between the breed
pair Bikaneri and Jaisalmeri which was closely placed with the Kachchhi breed.
The Mewari camels had relatively higher genetic distance from the other three
Indian dromedary breeds. The bottleneck analysis revealed the presence of genetic
bottleneck in all four breeds of Indian dromedary. However, the qualitative
graphical method resulted in normal L-shaped distribution of allele frequencies
in Jaisalmeri breeds and shifted mode in Bikaneri, Kachchhi and Mewari breeds.
The demographic bottleneck analysis revealed minimum reduction (-9.65 %) in the
population of camels in Jaisalmeri breeding tract as compared to that of Bikaneri
(-14.18 %), Kachchhi (-27.78 %) and Mewari (-32 %) breeding tracts. Conclusively,
the genetic bottleneck analysis could explain the demographic bottleneck in the
Indian dromedary populations. Therefore, appropriate conservation and improvement
efforts are needed in all four dromedary breeds with immediate attention on
Mewari and Kachchhi breeds. The present study is the first report in
demonstrating the genetic basis of demographic bottleneck in the Indian dromedary
populations.
PMID- 25134806
TI - Short-wave solar radiation level willingly tolerated by lactating Holstein cows
in an equatorial semi-arid environment.
AB - The amount of short-wave solar radiation willingly tolerated by lactating
Holstein cows on pasture was determined in an equatorial semi-arid environment.
The study was carried out on a dairy farm located in Limoeiro do Norte, CE,
northeastern Brazil. The observed behaviours were as follows: grazing, under the
sun, under the shade, standing, lying, ruminating, idling and wallowing in the
water. The behaviours were recorded using instantaneous scan sampling at regular
intervals of 15 min from 0600 to 1800 hours over 5 days. On all sampling days,
the meteorological variables, including local short-wave solar radiation (R S-W,
W m(-2)), were recorded. The R S-W data were divided into five levels. The sun
exposure was more frequent under low (100 %) and moderately low (97 %) levels,
when R S-W remained below 500 W m(-2). The grazing was more intense under low
(100 %) and moderately low (93 %) levels. Above 500 W m(-2), the grazing time
significantly decreased (11 %). The cows avoided grazing under high (0 %) and
very high (0 %) levels, when R S-W exceeded 700 W m(-2). The ruminating behaviour
was more frequent under high (33 %) and very high (37 %) levels, in which the
highest averages of R S-W were recorded (815 and 958 W m(-2), respectively). The
standing posture was more frequent under low (100 %) and moderately low (97 %)
levels. Therefore, the critical R S-W level that motivates cows to stop grazing
and seek shade was in the interval between 500 and 700 W m(-2).
PMID- 25134808
TI - Single-Tablet Regimens in HIV Therapy.
AB - Combined antiretroviral therapy (cART) has evolved considerably over the past
decades leading to a better control of human immunodeficiency virus replication.
Recently, regimens have evolved so as to simplify dosing frequency and reduce
pill burden to improve adherence. Several national and international guidelines
suggest antiretroviral (ARV) regimen simplification as a method of improving
adherence. Decreased cART adherence has been associated with both patient-related
factors and regimen-related factors. Adherence rates are statistically higher
when simpler, once-daily (OD) regimens are combined with smaller daily regimen
pill burdens. The avoidance of selective non-adherence, where a patient takes
part of a regimen but not the full regimen, is a further potential benefit
offered by single-tablet regimens (STRs). Simplification of cART has been
associated with a better quality of life (QoL). Although tempered by other
factors, better adherence, higher QoL and patients' preferences are all key
points which might combine to assure long-lasting efficacy and durability of
cART. All studies underlined the favorable tolerability profile of newer STRs.
Three STRs are currently available. Tenofovir (TDF) plus emtricitabine
(FTC)/efavirenz (EFV) was the first OD complete ARV regimen available as a STR.
TDF plus FTC/rilpivirine is a second-generation STR. The most recently approved
STR, TDF plus FTC/cobicistat/elvitegravir, is the first non-nucleoside reverse
transcriptase inhibitor-based STR. All of them have shown excellent efficacy;
safety and tolerability have been improved by more recent formulations. Several
other STRs are anticipated both combining completely different drugs, abacavir
(ABC) plus lamivudine (3TC)/dolutegravir, utilizing innovative formulations of
older drugs, tenofovir alafenamide fumarate, or taking advance of bioequivalent
drugs, lamivudine (3TC) plus ABC/EFV. The future challenge would be to develop
completely alternative STRs (including for example protease inhibitors or new
molecules) to extend the advantages of simplicity to heavily pre-treated
individuals.
PMID- 25134809
TI - Epidemiology of pneumococcal disease in a national cohort of older adults.
AB - INTRODUCTION: Streptococcus pneumoniae is a major cause of morbidity and
mortality. We sought to describe the epidemiology of non-invasive and invasive
pneumococcal disease in a national Veterans Affairs population within the United
States. METHODS: We conducted a retrospective study in older patients (aged >=50
years) with positive pneumococcal cultures from any site between 2002 and 2011.
We described outpatient and inpatient pneumococcal disease incidence per 100,000
clinic visits/hospitalizations. Repeat cultures within a 30-day period were
considered to represent the same episode. To describe the epidemiology of serious
pneumococcal infections (bacteremia, meningitis, pneumonia), we assessed
demographics, clinical characteristics, and risk factors for S. pneumoniae.
Pneumonia was defined as a positive respiratory culture with a pneumonia
diagnosis code. Bacteremia and meningitis were identified from positive cultures.
Generalized linear mixed models were used to quantify changes over time. RESULTS:
Over the study period, we identified 45,983 unique episodes of pneumococcal
disease (defined by positive cultures). Incidence decreased significantly by 3.5%
per year in outpatients and increased non-significantly by 0.2% per year in
inpatients. In 2011, the outpatient and inpatient incidence was 2.6 and 328.1
infections per 100,000 clinic visits/hospitalizations, respectively. Among
inpatients with serious infections, chronic disease risk factors for pneumococcal
disease increased significantly each year, including respiratory disease (1.9%
annually), diabetes (1.3%), and renal failure (1.0%). Overall, 30.2% of
inpatients with serious infections had a pneumococcal immunization in the
previous 5 years. Invasive disease (37.4% versus 34.9%, P = 0.004) and mortality
(14.0% versus 12.7%, P = 0.045) were higher in non-vaccinated patients compared
to vaccinated patients. CONCLUSIONS: In our national study of older adults, the
baseline health status of those with serious pneumococcal infections worsened
over the study period. As the population ages and the chronic disease epidemic
grows, the burden of pneumococcal disease is likely to increase thus highlighting
the importance of pneumococcal vaccination.
PMID- 25134811
TI - Impact of a Multidisciplinary Culture Follow-up Program of Antimicrobial Therapy
in the Emergency Department.
AB - INTRODUCTION: Antimicrobial prescribing in the emergency department is
predominantly empiric, with final microbiology results either unavailable or
reported after most patients are discharged home. Systematic follow-up processes
are needed to ensure appropriate antimicrobial therapy at this transition of
care. The objective of this study was to assess the impact of a culture follow-up
(CFU) program on the frequency of emergency department (ED) revisits within 72 h
and hospital admissions within 30 days compared to the historical standard of
care (SOC). Additionally, infection characteristics and antimicrobial therapy
were compared. METHODS: A single group, pre-test post-test quasi-experimental
study was conducted comparing a retrospective SOC group to a prospective CFU
group. CFU was implemented using computerized decision-support software and a
multidisciplinary team of pharmacists and emergency physician staff. RESULTS:
Over the four-month intervention period the CFU group evaluated 197 cultures and
modified antimicrobial therapy in 25.5%. The rate of combined ED revisits within
72 h and hospital admissions within 30 days was 16.9% in the SOC group and 10.2%
in the CFU group (p = 0.079). When evaluating the uninsured population alone,
revisits to the ED within 72 h were reduced from 15.3% in the SOC group to 2.4%
in the CFU group (p = 0.044). CONCLUSION: Implementation of a multidisciplinary
CFU program was associated with a reduction in ED revisits within 72 h and
hospital admissions within 30 days. One-fourth of patients required post
discharge intervention, representing a large need for antimicrobial stewardship
expansion to ED practice models.
PMID- 25134810
TI - Observation of "seesaw effect" with vancomycin, teicoplanin, daptomycin and
ceftaroline in 150 unique MRSA strains.
AB - INTRODUCTION: Vancomycin (VAN) failures associated with the treatment of
complicated methicillin-resistant Staphylococcus aureus (MRSA) infections have
been well described. The reported "seesaw effect" demonstrates improved beta
lactam activity when VAN and/or daptomycin (DAP) susceptibility decreases.
However, there are minimal data comparing ceftaroline (CPT) susceptibility with
these agents or teicoplanin (TEI). Therefore, to further explore the seesaw
effect, we evaluated the relationship between CPT and VAN, TEI, and DAP
susceptibilities. METHODS: One hundred and fifty clinical MRSA isolates from the
Anti-Infective Research Laboratory (Detroit, MI, USA) from 2008 to 2012 were
analyzed. VAN, TEI, DAP and CPT minimum inhibitory concentrations (MIC) were
determined via Etest methodology. MIC50 and MIC90 were calculated for each
antibiotic. Additionally, four isogenic strain pairs were randomly selected for
evaluation by time-kill methodology for the potential of enhanced killing by CPT
as MICs increased to VAN, TEI, and DAP. RESULTS: CPT MICs were inversely
correlated with VAN, DAP, and TEI MICs with correlation coefficients of -0.535,
0.483, and -0.386, respectively (P <= 0.05). Comparison of the MIC relationship
for glycopeptides and lipopeptides resulted in a positive correlation for all
agent combinations. In time-kill evaluations, CPT demonstrated greater reductions
in log10 colony-forming unit (CFU)/mL against mutant strains (3.73 +/- 0.67)
versus parents (2.79 +/- 0.75) despite no change in CPT MIC (P = 0.112).
CONCLUSION: This study demonstrated a marked "seesaw effect" whereby CPT
displayed increased susceptibility as the VAN, DAP, and TEI MICs increased.
Additionally, we observed a positive linear correlation between VAN, DAP, and TEI
MICs for all agent combinations. Enhanced activity was noted with CPT in mutant
strains versus the parent strains despite no change in MIC. Based upon the
enhanced CPT activity observed against strains with decreased susceptibility to
VAN, DAP and TEI, CPT may provide an option for infections with reduced
susceptibility to glycopeptides or lipopeptides. Further evaluation is warranted
to investigate the clinical implications of the seesaw effect.
PMID- 25134812
TI - Lack of Change in Susceptibility of Pseudomonas aeruginosa in a Pediatric
Hospital Despite Marked Changes in Antibiotic Utilization.
AB - INTRODUCTION: It is assumed that a direct relationship exists between the extent
of use of any given antibiotic or antibiotic class and the degree of
susceptibility or resistance on the part of various bacteria to that antibiotic
or class. METHODS: Pseudomonas aeruginosa susceptibility rates and utilization of
key antipseudomonal antibiotics in a pediatric hospital, reflected as grams/1,000
patient days, were studied over a 7-year period. RESULTS: While the volume of use
of a number of antibiotics changed dramatically over this time period,
susceptibility of Pseudomonas to these same agents remained relatively stable.
The use of aminoglycosides decreased 14.5% while that of piperacillin/tazobactam
increased 92% over the period of observation while susceptibility generally
varied by <10%. CONCLUSION: Contrary to popular belief, changes in antibiotic
utilization patterns do not always result in changes in susceptibility thus
emphasizing the importance of continual institutional monitoring of antibiotic
use and susceptibility patterns.
PMID- 25134813
TI - Erratum to: Epidemiology of Pneumococcal Disease in a National Cohort of Older
Adults.
PMID- 25134815
TI - NMR and molecular dynamics study of the size, shape, and composition of reverse
micelles in a cetyltrimethylammonium bromide (CTAB)/n-hexane/pentanol/water
microemulsion.
AB - The size, shape, and composition of reverse micelles (RMs) in a
cetyltrimethylammonium bromide (CTAB)/pentanol/n-hexane/water microemulsion were
investigated using pulsed gradient stimulated echo (PGSTE) nuclear magnetic
resonance (NMR) measurements and molecular modeling. PGSTE data were collected at
observation times (Delta) of 10, 40, and 450 ms. At long observation times, CTAB
and pentanol exhibited single diffusion coefficients. However, at short (Delta <=
40 ms) observation times both CTAB and pentanol exhibited slow and fast diffusion
coefficients. These NMR data indicate that both CTAB and pentanol molecules
reside in different environments within the microemulsion and that there is
exchange between regions on the millisecond time scale. Molecular dynamic
simulations of the CTAB RM, in a solvent box containing n-hexane and pentanol,
produced an ellipsoid shaped RM. Using structural parameters from these
simulations and the Stokes-Einstein relation, the structure factor and dimensions
of the reverse micelle were determined. Analysis of the composition of the
interphase also showed that there was a variation in the ratio of surfactant to
cosurfactant molecules depending on the curvature of the interphase.
PMID- 25134816
TI - Interobserver and intraobserver reliability of the radiographic analysis of
femoroacetabular impingement and dysplasia using computer-assisted measurements.
AB - BACKGROUND: A comprehensive evaluation of hip radiographs in the young adult with
hip pain has become increasingly complex and time consuming. The interobserver
reliability of manually performed measurements of femoroacetabular impingement,
including the alpha angle, has been questioned. Methods to improve the
reliability of a radiographic evaluation may increase the clinical utility of
these parameters. PURPOSE: To determine the interobserver and intraobserver
reliability of a computer-assisted radiographic analysis of the young adult hip
in a clinically relevant setting. STUDY DESIGN: Cohort study (diagnosis); Level
of evidence, 3. METHODS: A reliability study of a comprehensive computer-assisted
radiographic evaluation was performed, which included 25 radiographic parameters
of proximal femoral morphology, acetabular morphology, hip osteoarthritis, and
pelvic tilt/rotation. Anteroposterior pelvis and 45 degrees Dunn lateral
radiographs of 70 consecutive patients undergoing hip preservation surgery were
included. Each radiograph was analyzed by 4 experienced hip surgeons. The
reliability of continuous measurements was analyzed using intraclass correlation
coefficients (ICCs), while categorical parameters were analyzed using kappa
values and percentages of agreement. RESULTS: The interobserver reliability of
the parameters of proximal femoral morphology, acetabular morphology, and
osteoarthritis was generally substantial to excellent. Parameters with lesser
interobserver reliability included the alpha angle (ICC, 0.43), Tonnis
osteoarthritis classification (kappa = 0.22), and classification of pelvic tilt
(using the coccyx or sacrococcygeal joint) (kappa = 0.43 and 0.61, respectively).
CONCLUSION: A computer-assisted analysis of young adult hip radiographs generally
demonstrates substantial to excellent levels of interobserver reliability for
most parameters. However, alpha angle measurements demonstrated only moderate
interobserver reliability, despite excellent intraobserver reliability.
Measurements of the joint space width appear to be significantly more reliable
than the use of the Tonnis osteoarthritis classification in this population. The
classification of pelvic tilt utilizing the coccyx or sacrococcygeal joint is
only moderately reliable.
PMID- 25134817
TI - Concentration-dependent effects of spermine on apoptosis and consequent
generation of multilayer myotube sheets from mouse embryoid bodies in vitro.
AB - The concentration-dependent effect of spermine was investigated on the spermine
induced generation of multilayer myotube sheets (MMTS) from mouse embryoid bodies
(EBs). During spermine treatment for 24 h, a monolayer cell sheet that had
already grown radially from the periphery of an EB was exfoliated. The
exfoliation was inhibited by z-VAD.fmk, indicating the occurrence of apoptosis,
and inhibited also by aminoguanidine, indicating the involvement of amine
oxidase. Following the exfoliation, the cell growth restarted from the fresh
periphery of EB in a spermine-free medium and finally formed MMTS. To analyze the
contribution of apoptosis to the cell death causing exfoliation, the numbers of
apoptotic, necrotic, and 2nd apoptotic cells were counted by staining with
Annexin V-Cyanine-3 (AVC3) and 7-aminoactinomycin (7AAC). AVC3-positive, 7AAC
positive, and AVC3/7AAC doubly positive cells were assigned as apoptotic,
necrotic, and 2nd necrotic cells, respectively. The relative number of apoptotic
and 2nd necrotic cells (N A + N A/7) to the total number of dying cells (N T) was
84 ~ 94%, which was independent of spermine concentration in the range from 0.1
to 2.0 mM. The MMTS generation rate at the final stage, however, was dependent on
the spermine concentration. It was 60 ~ 80% in the range from 0.1 to 1.5 mM,
while it decreased sharply to 1% at 2 mM. This suggests another role of spermine
in the MMTS generation in addition to the induction of apoptosis. This 2nd role
seems to be inhibited at a spermine concentration higher than a critical limit
between 1.5 and 2.0 mM.
PMID- 25134818
TI - The expression of pluripotency genes and neuronal markers after
neurodifferentiation in fibroblasts co-cultured with human umbilical cord blood
mononuclear cells.
AB - Human umbilical cord blood is an attractive source of stem cells; however, it has
a heterogeneous cell population with few mesenchymal stem cells. Cell
reprogramming induced by different methodologies can confer pluripotency to
differentiated adult cells. The objective of this study was to evaluate the
reprogramming of fibroblasts and their subsequent neural differentiation after co
culture with umbilical cord blood mononuclear cells. Cells were obtained from
four human umbilical cords. The mononuclear cells were cultured for 7 d and
subsequently co-cultured with mouse fibroblast NIH-3T3 cells for 6 d. The
pluripotency of the cells was evaluated by RT-PCR using primers specific for
pluripotency marker genes. The pluripotency was also confirmed by adipogenic and
osteogenic differentiation. Neural differentiation of the reprogrammed cells was
evaluated by immunofluorescence. All co-cultured cells showed adipogenic and
osteogenic differentiation capacity. After co-cultivation, cells expressed the
pluripotency gene KLF4. Statistically significant differences in cell area,
diameter, optical density, and fractal dimension were observed by confocal
microscopy in the neurally differentiated cells. Contact in the form of co
cultivation of fibroblasts with umbilical cord blood mononuclear fraction for 6 d
promoted the reprogramming of these cells, allowing the later induction of neural
differentiation.
PMID- 25134819
TI - Healthy HIV-1-infected individuals on highly active antiretroviral therapy harbor
HIV-1 in their alveolar macrophages.
AB - In a prospective cross-sectional study we quantified HIV viral load within the
alveolar macrophage in a cohort of healthy HIV-infected subjects who did not have
medical comorbidities or smoke cigarettes to determine if alveolar macrophage
proviral DNA was associated with alveolar macrophage phagocytic immune
dysfunction. We enrolled 23 subjects who underwent bronchoscopy and
bronchoalveolar lavage. Alveolar macrophages were isolated and HIV-1 RNA was
quantified in the cells using the Abbott RealTime HIV-1 Assay. Proviral DNA was
qualitatively measured using a modified version of the HIV-1 RNA assay.
Phagocytosis measured by incubating alveolar macrophages with FITC-labeled
Staphylococcus aureus and determining fluorescence with a Zeiss inverted
microscope. Phagocytic index was calculated as (% positive cells * mean channel
fluorescence)/100. Sixteen subjects had (+) proviral DNA and seven had (-)
proviral DNA in their alveolar macrophages. Of all subjects 100% in both groups
were on highly active antiretroviral therapy (HAART). The median plasma viral
load was 0 in both groups. HIV-1-infected subjects with (+) proviral DNA in their
alveolar macrophages had a significantly lower median alveolar macrophage
phagocytic index compared to those with (-) proviral DNA in their alveolar
macrophages [11.8 (IQR 4.8-39.0) vs. 64.9 (IQR 14.0-166.0), p = 0.05]. Alveolar
macrophages harbor HIV even in otherwise healthy subjects with undetectable
plasma viral loads, representing a potential reservoir for the virus. In
addition, HIV viral replication within the macrophage may impair phagocytosis and
other immune functions in the lung, leading to an increased risk for lung
infection.
PMID- 25134820
TI - Treatment of camptocormia with continuous subcutaneous infusions of apomorphine:
1-year prospective pilot study.
AB - Camptocormia is defined as a marked dystonic flexion of the trunk in the sagittal
plane. Camptocormia responds poorly to botulinum toxin injections, manipulation
with dopaminergic treatment, and deep brain stimulation. We designed a
prospective pilot study to assess the effect of apomorphine infusions on
camptocormia. Five patients were enrolled. All five patients responded well to
this treatment. The fact that camptocormia responds so well to apomorphine may be
explained by the sustained stimulation of the ventrolateral striatal D1
receptors, alleviating this type of dystonia.
PMID- 25134821
TI - Methylome analysis identifies a Wilms tumor epigenetic biomarker detectable in
blood.
AB - BACKGROUND: Wilms tumor is the most common pediatric renal malignancy and there
is a clinical need for a molecular biomarker to assess treatment response and
predict relapse. The known mutated genes in this tumor type show low mutation
frequencies, whereas aberrant methylation at 11p15 is by far the most common
aberration. We therefore analyzed the epigenome, rather than the genome, to
identify ubiquitous tumor-specific biomarkers. RESULTS: Methylome analysis of
matched normal kidney and Wilms tumor identifies 309 preliminary methylation
variable positions which we translate into three differentially methylated
regions (DMR) for use as tumor-specific biomarkers. Using two novel algorithms we
show that these three DMRs are not confounded by cell type composition. We
further show that these DMRs are not methylated in embryonic blastema but are
intermediately methylated in Wilms tumor precursor lesions. We validate the
biomarker DMRs using two independent sample sets of normal kidney and Wilms tumor
and seven Wilms tumor histological subtypes, achieving 100% and 98% correct
classification, respectively. As proof-of-principle for clinical utility, we
successfully use biomarker DMR-2 in a pilot analysis of cell-free circulating DNA
to monitor tumor response during treatment in ten patients. CONCLUSIONS: These
findings define the most common methylated regions in Wilms tumor known to date
which are not associated with their embryonic origin or precursor stage. We show
that this tumor-specific methylated DNA is released into the blood circulation
where it can be detected non-invasively showing potential for clinical utility.
PMID- 25134822
TI - A comparison of linkage to HIV care after provider-initiated HIV testing and
counselling (PITC) versus voluntary HIV counselling and testing (VCT) for
patients with sexually transmitted infections in Cape Town, South Africa.
AB - BACKGROUND: We examined linkage to care for patients with sexually transmitted
infection who were diagnosed HIV-positive via the provider-initiated HIV testing
and counselling (PITC) approach, as compared to the voluntary counselling and
testing (VCT) approach, as little is known about the impact of expanded testing
strategies on linkage to care. METHODS: In a controlled trial on PITC (Cape Town,
2007), we compared HIV follow-up care for a nested cohort of 930 HIV-positive
patients. We cross-referenced HIV testing and laboratory records to determine
access to CD4 and viral load testing as primary outcomes. Secondary outcomes were
HIV immune status and time taken to be linked to HIV care. Logistic regression
was performed to analyse the difference between arms. RESULTS: There was no
difference in the main outcomes of patients with a record of CD4 testing (69.9%
in the intervention, 65.2% in control sites, OR 0.82 (CI: 0.44-1.51; p = 0.526)
and viral load testing (14.9% intervention versus 10.9% control arm; OR 0.69 (CI:
0.42-1.12; p = 0.131). In the intervention arm, ART-eligible patients (based on
low CD4 test result), accessed viral load testing approximately 2.5 months sooner
than those in the control arm (214 days vs. 288 days, HR: 0.417, 95% CI: 0.221
0.784; p = 0.007). CONCLUSION: The PITC intervention did not improve linkage to
CD4 testing, but shortened the time to viral load testing for ART-eligible
patients. Major gaps found in follow-up care across both arms, indicate the need
for more effective linkage-to-HIV care strategies. TRIAL REGISTRATION: Current
Controlled Trials ISRCTN93692532.
PMID- 25134823
TI - Exploring repeat HIV testing among men who have sex with men in Cape Town and
Port Elizabeth, South Africa.
AB - Despite the high prevalence of HIV among men who have sex with men (MSM) - and
the general adult population - in South Africa, there is little data regarding
the extent to which MSM seek repeat testing for HIV. This study explores reported
histories of HIV testing, and the rationales for test seeking, among a purposive
sample of 34 MSM in two urban areas of South Africa. MSM participated in activity
based in-depth interviews that included a timeline element to facilitate
discussion. Repeat HIV testing was limited among participants, with three
quarters having two or fewer lifetime HIV tests, and over one-third of the sample
having one or fewer lifetime tests. For most repeat testers, the time gap between
their HIV tests was greater than the one-year interval recommended by national
guidelines. Analysis of the reasons for seeking HIV testing revealed several
types of rationale. The reasons for a first HIV test were frequently one-time
occurrences, such as a requirement prior to circumcision, or motivations likely
satisfied by a single HIV test. For MSM who reported repeat testing at more
timely intervals, the most common rationale was seeking test results with a sex
partner. Results indicate a need to shift HIV test promotion messaging and
programming for MSM in South Africa away from a one-off model to one that frames
HIV testing as a repeated, routine health maintenance behavior.
PMID- 25134824
TI - Galla Chinensis attenuates cigarette smoke-associated lung injury by inhibiting
recruitment of inflammatory cells into the lung.
AB - Inflammation is a common feature in the pathogenesis of cigarette smoke (CS)
associated diseases. In this study, we investigated the effects of Galla
Chinensis (GC) extract on pulmonary inflammatory responses in a CS-exposed mouse
model. In vitro studies showed that GC extract reduced MCP-1 production in a dose
dependent manner. In addition, the recruitment of inflammatory cells into the
lung was significantly inhibited in the bronchoalveolar lavage fluid (BALF) of
the GC-treated mice after 3 weeks of daily CS exposure. GC treatment down
regulated TNF-alpha, IL-6 and MCP-1 mRNA expression levels in lung tissue.
Finally, GC-treated mice showed less emphysematous change of alveolar compared to
mice only exposed to CS. Our results show that GC extract reduces lung
inflammation and emphysematous change by inhibiting the infiltration of
inflammatory cells to the lung. These data indicate that GC extract is a
therapeutic candidate for CS-induced lung injury.
PMID- 25134825
TI - Diastereoselective synthesis of N-(p-tosylsulfonyl)-2-phenylaziridine over a
novel magnetically recyclable Cu(II) catalyst accompanied with the N-inversion
assessment at DFT.
AB - An experimental and theoretical study has been carried out on diastereoselective
aziridation of styrene over a magnetically recyclable copper(II) catalyst:
Cu(acac)2/NH2-T/SiO2@Fe3O4NPs. The turnover number (TON) of our heterogeneous
catalyst appears considerably higher than that reported for the homogeneous
Cu(acac)2. Successive applications of solid Cu(acac)2/NH2-T/SiO2@Fe3O4NPs have a
slight effect on its catalytic activity. Between anticipated cis and trans
diastereomeric products, formation of only one is suggested by NMR. Even though,
the trans-invertomer appears thermodynamically more stable at B3LYP/AUG-cc
pVTZ//B3LYP/6-31+G+G* level, we propose formation of the kinetically more stable
cis-invertomer due to pi-stacking between the tosyl group and the phenyl of
styrene. The possibility of cis-trans conversion is ruled out by the high energy
barrier of > 76.9 kcal/mol probed in toluene, CCl4, C7H16, DMSO, CH3CN, and H2O.
PMID- 25134826
TI - Temperature dependent reversible p-n-p type conduction switching with colossal
change in thermopower of semiconducting AgCuS.
AB - Semiconductors have been fundamental to various devices that are typically
operated with electric field, such as transistors, memories, sensors, and
resistive switches. There is growing interest in the development of novel
inorganic materials for use in transistors and semiconductor switches, which can
be operated with a temperature gradient. Here, we show that a crystalline
semiconducting noble metal sulfide, AgCuS, exhibits a sharp temperature dependent
reversible p-n-p type conduction switching, along with a colossal change in the
thermopower (DeltaS of ~1757 MUV K(-1)) at the superionic phase transition (T of
~364 K). In addition, its thermal conductivity is ultralow in 300-550 K range
giving AgCuS the ability to maintain temperature gradients. We have developed
fundamental understanding of the phase transition and p-n-p type conduction
switching in AgCuS through temperature dependent synchrotron powder X-ray
diffraction, heat capacity, Raman spectroscopy, and positron annihilation
spectroscopy measurements. Using first-principles calculations, we show that this
rare combination of properties originates from an effective decoupling of
electrical conduction and phonon transport associated with electronic states of
the rigid sulfur sublattice and soft vibrations of the disordered cation
sublattices, respectively. Temperature dependent p-n-p type conduction switching
makes AgCuS an ideal material for diode or transistor devices that operate
reversibly on temperature or voltage changes near room temperature.
PMID- 25134827
TI - KeyPathwayMiner 4.0: condition-specific pathway analysis by combining multiple
omics studies and networks with Cytoscape.
AB - BACKGROUND: Over the last decade network enrichment analysis has become popular
in computational systems biology to elucidate aberrant network modules.
Traditionally, these approaches focus on combining gene expression data with
protein-protein interaction (PPI) networks. Nowadays, the so-called omics
technologies allow for inclusion of many more data sets, e.g. protein
phosphorylation or epigenetic modifications. This creates a need for analysis
methods that can combine these various sources of data to obtain a systems-level
view on aberrant biological networks. RESULTS: We present a new release of
KeyPathwayMiner (version 4.0) that is not limited to analyses of single omics
data sets, e.g. gene expression, but is able to directly combine several
different omics data types. Version 4.0 can further integrate existing knowledge
by adding a search bias towards sub-networks that contain (avoid) genes provided
in a positive (negative) list. Finally the new release now also provides a set of
novel visualization features and has been implemented as an app for the standard
bioinformatics network analysis tool: Cytoscape. CONCLUSION: With KeyPathwayMiner
4.0, we publish a Cytoscape app for multi-omics based sub-network extraction. It
is available in Cytoscape's app store
http://apps.cytoscape.org/apps/keypathwayminer or via http://keypathwayminer.mpi
inf.mpg.de.
PMID- 25134828
TI - Factors associated with genital human papillomavirus infection among adult
females in the United States, NHANES 2007-2010.
AB - BACKGROUND: Patients with human papillomavirus (HPV) infection are at risk of
developing cancer later in their life. Current research estimates the prevalence
of genital HPV infection and explores the factors that are associated with the
infection. FINDINGS: The National Health and Nutrition Examination Survey 2007
2010 was used in this research study. The study population included females in
the United States aged 18-59 years. The weighted prevalence of HPV infection was
41.9%. An estimated 59.4% of non-Hispanic black females had HPV infection. In a
multivariate analysis, number of sexual partners, race, age, education level,
marital status, income, smoking, and insurance status were associated with HPV
infection. HPV infection was 5.77 times more likely for women with >11 sexual
partners compared to women with 0-1 partners. Non-Hispanic black females were
1.87 times more likely to have HPV infection compared to non-Hispanic white
females. Participants with only a high school degree had a 58% increased
prevalence compared to college-educated women. Uninsured women had a 39%
increased prevalence compared to those with insurance. CONCLUSION: This study
found that 41.9% of U.S. females aged 18-59 years tested positive for genital HPV
infection. We determined that individuals with more sexual partners, with a lower
education level, with non-Hispanic black race, and with no insurance were the
populations at greatest risk. It is necessary to continue monitoring the
prevalence of this infection in the general population to provide a basis for
effective treatment and prevention in the target populations.
PMID- 25134831
TI - Prostate cancer: Optimizing fluorescence guidance in sentinel node biopsy.
PMID- 25134829
TI - Autophagy as a modulator and target in prostate cancer.
AB - Autophagy, or 'self-eating', is an adaptive process that enables cells to cope
with metabolic, toxic, and even infectious stressors. Although the adaptive
capability of autophagy is generally considered beneficial, autophagy can also
enhance nutrient utilization and improve growth characteristics of cancer cells.
Moreover, autophagy can promote greater cellular robustness in the context of
therapeutic intervention. In advanced prostate cancer, preclinical data provide
evidence that autophagy facilitates both disease progression and therapeutic
resistance. Notably, androgen deprivation therapy, taxane-based chemotherapy,
targeted kinase inhibition, and nutrient restriction all induce significant
cellular distress and, subsequently, autophagy. Understanding the context
dependent role of autophagy in cancer development and treatment resistance has
the potential to improve current treatment of advanced prostate cancer. Indeed,
preclinical studies have shown that the pharmacological inhibition of autophagy
(with agents including chloroquine, hydroxychloroquine, metformin, and
desmethylclomipramine) can enhance the cell-killing effect of cancer
therapeutics, and a number of these agents are currently under investigation in
clinical trials. However, many of these autophagy modulators are relatively
nonspecific, and cytotoxicity in noncancerous tissues is still a concern. Moving
forward, refinement of autophagy modulation is needed.
PMID- 25134833
TI - Paediatrics: A 24 h urine collection is essential in nephrolithiasis evaluation.
PMID- 25134834
TI - Prostate cancer: PSA update--no change yet.
PMID- 25134837
TI - Paediatric urology: Evasive manoeuvres from bacteria in urinary tract infection.
PMID- 25134839
TI - External abdominal oblique muscle ultrasonographic thickness changes is not an
appropriate surrogate measure of electromyographic activity during isometric
trunk contractions.
AB - BACKGROUND: The function of specific abdominal muscles can be assessed using both
electromyography (EMG) and ultrasound imaging (USI) thickness measures. However,
the relationship between these two measurements is not conclusive during sitting
isometric trunk efforts. OBJECTIVE: This study was conducted to assess the
relationship between USI thickness and EMG amplitude measures of the right
external oblique (EO) muscle during isometric efforts in the sitting position.
METHOD: Eighteen subjects performed ramp isometric efforts progressing from 0 to
50% of their maximal voluntary contraction (MVC) in three trunk directions on a
dynamometer: (1) forward flexion; (2) right lateral flexion; and (3) left axial
rotation. USI and surface EMG amplitude measures of the EO muscle were recorded
concomitantly and both normalized against rest values and maximal EMG,
respectively. RESULTS: EO muscle was significantly more activated (p < 0.001)
during forward flexion (42% on average) and axial rotation (35%) than during
lateral flexion (24%). Non-significant (r=0.01; P=0.979) to highly significant
(r=0.98; P < 0.0001) and negative and positive Pearson correlations were observed
between EMG and EO thickness measures for both flexion and rotation directions.
CONCLUSION: The negative correlations between EMG and USI measures as well as the
great variability of these correlations across individuals suggest that USI is
not a valid measures of EO muscle activity. USI thickness measures should be
interpreted with great caution in research and clinical settings.
PMID- 25134840
TI - Effect of grain orientations of Cu seed layers on the growth of <111>-oriented
nanotwinned Cu.
AB - We investigate the growth of Cu films on two different Cu seed layers: one with
regular <111>-oriented grains and the other with very strong <111>-preferred
orientation. It is found that densely-packed nanotwinned Cu (nt-Cu) can be grown
by pulsed electroplating on the strong <111>-oriented Cu seed layer without a
randomly-oriented transition layer between the nt-Cu and the Cu seed layer. The
electroplated nt-Cu grow almost epitaxially on the seed layer and formed <111>
oriented columnar structures. However, with the regular <111>-oriented Cu seed,
there is a randomly-oriented transition layer between the nt-Cu and the regular
<111>-oriented Cu seed. The results indicate that the seed layer plays a crucial
role on the regularity of <111>-oriented nanotwinned Cu.
PMID- 25134842
TI - Differences between adults and children: genetics and beyond.
AB - Clinical observations and epidemiological studies have highlighted some important
differences in disease course and phenotypes between pediatric inflammatory bowel
disease (IBD) and adult-onset IBD. Also from a therapeutic angle, the approach to
young-onset IBD is different with a more rapid introduction of azathioprine and a
high threshold for long and systemic steroid use, which may affect bone mineral
density and growth. The observed clinical differences have been an area of
scientific research and genetic studies have been the focus of attention.
Specific candidate gene studies as well as genome-wide association studies have
been performed in pediatric IBD. With the exception of very early-onset IBD
occurring before the age of 2 years; no overt differences in genetic
susceptibility have been identified. In contrast, very early-onset IBD seems in
particular to be a genetic disease with defects in the IL10 signaling pathway
being the principal example. This review aims to answer some straightforward
questions arising in this topic by giving concise information.
PMID- 25134843
TI - Sub-regional volumes changes of the corpus callosum in the drug naive patients
with late-onset depression.
AB - Although sub-regional analysis methods of the corpus callosum (CC) have been
developed, there has been no in vivo magnetic resonance imaging (MRI) study on a
sub-regional volume analysis of the CC of late-onset depression (LOD). The aim of
this study was to investigate the CC volume differences between LOD subjects and
healthy elderly controls using a sub-regional analysis technique. Forty subjects
with LOD and thirty nine group-matched healthy control subjects underwent 3T MRI
scanning, and sub-regional volumes of the CC were measured and compared between
the groups. The volumes of total (F=5.8, p=0.001), the anterior (F=5.2, p=0.001)
and the posterior CC (F=5.1, p=0.001) were significantly reduced in the LOD group
as compared to the control group. We measured cognitive functions in several
different domains (language functions, verbal learning, visuospatial functions,
delayed recall, memory consolidation, recognition memory, and executive
functions) through the Korean version of the Consortium to Establish a Registry
for Alzheimer's Disease. The anterior CC volume in the LOD group showed
significant positive correlation with the Verbal Fluency scores. The posterior CC
volume in the LOD group was positively correlated significantly with the Word
List Memory, the Word List Recall and the Constructional Praxis scores. This
study is the first to elaborate the sub-regional volume differences of the CC
between controls and LOD patients. These structural changes in the CC might be at
the core of the underlying neurobiological mechanisms in LOD.
PMID- 25134844
TI - Randomised controlled trials: inferring significance of treatment effects based
on confidence intervals.
PMID- 25134845
TI - Tailoring the topology of an artificial magnetic skyrmion.
AB - Despite theoretical predictions, it remains an experimental challenge to realize
an artificial magnetic skyrmion whose topology can be well controlled and
tailored so that its topological effect can be revealed explicitly in a
deformation of the spin textures. Here we report epitaxial magnetic thin films in
which an artificial skyrmion is created by embedding a magnetic vortex into an
out-of-plane aligned spin environment. By changing the relative orientation
between the central vortex core polarity and the surrounding out-of-plane spins,
we are able to control and tailor the system between two skyrmion topological
states. An in-plane magnetic field is used to annihilate the skyrmion core by
converting the central vortex state into a single domain state. Our result shows
distinct annihilation behaviour of the skyrmion core for the two different
skyrmion states, suggesting a topological effect of the magnetic skyrmions in the
core annihilation process.
PMID- 25134838
TI - NUMB inhibition of NOTCH signalling as a therapeutic target in prostate cancer.
AB - Prostate cancer is among the most prevalent life-threatening cancers diagnosed in
the male population today. Various methods have been exploited in an attempt to
treat this disease but these treatments, alongside preventative tactics, have
been insufficient to control mortality rates and have usually resulted in
detrimental adverse events. An opportunity to devise more-specific and
potentially more-effective approaches for the eradication of prostate tumours can
be found by targeting specific biological pathways. NUMB (protein numb
homologue), a key regulator of cell fate, represents an attractive, actionable
target in prostate cancer. NUMB participates in the observed deregulation of
NOTCH (neurogenic locus notch homologue protein) signalling in prostate tumours,
and the NUMB-NOTCH interaction regulates cell fate. NUMB has potential both as a
target for control of prostate tumorigenesis and as a biomarker for
identification of patients with prostate cancer who are likely to benefit from
NOTCH inhibition.
PMID- 25134846
TI - Thyroglobulin autoantibodies switch to immunoglobulin (Ig)G1 and IgG3 subclasses
and preserve their restricted epitope pattern after 131I treatment for Graves'
hyperthyroidism: the activity of autoimmune disease influences subclass
distribution but not epitope pattern of autoantibodies.
AB - The subclass distribution of thyroglobulin autoantibodies (TgAb) is debated,
whereas their epitope pattern is restricted. Radioidine ((131)I) treatment for
Graves' disease (GD) induces a rise in TgAb levels, but it is unknown whether it
modifies subclass distribution and epitope pattern of TgAb as well. We collected
sera from GD patients before (131) I treatment and 3 and 6 months thereafter. We
measured total TgAb, TgAb light chains and TgAb subclasses by enzyme-linked
immunosorbent assay (ELISA) in 25 patients. We characterized the TgAb epitope
pattern in 30 patients by inhibiting their binding to (125-) (I) Tg by a pool of
four TgAb-Fab (recognizing Tg epitope regions A, B, C and D) and to Tg in ELISA
by each TgAb-Fab. Total TgAb immunoglobulin (Ig)G rose significantly (P = 0.024).
TgAb kappa chains did not change (P = 0.052), whereas TgAb lambda chains
increased significantly (P = 0.001) and persistently. We observed a significant
rise in IgG1 and IgG3 levels after (131)I (P = 0.008 and P = 0.006,
respectively), while IgG2 and IgG4 levels did not change. The rise of IgG1 was
persistent, that of IgG3 transient. The levels of inhibition of TgAb binding to
Tg by the TgAb-Fab pool were comparable. A slight, non-significant reduction of
the inhibition by the immune-dominant TgAb-Fab A was observed 3 and 6 months
after (131)I. We conclude that (131)I treatment for GD increases the levels of
the complement-activating IgG1 and IgG3 subclasses and does not influence
significantly the epitope pattern of TgAb. In autoimmune thyroid disease subclass
distribution of autoantibodies is dynamic in spite of a stable epitope pattern.
PMID- 25134847
TI - Effects of Enteromyxum scophthalmi experimental infection on the neuroendocrine
system of turbot, Scophthalmus maximus (L.).
AB - Enteromyxum scophthalmi is an intestinal myxosporean parasite responsible for
serious outbreaks in turbot Scophthalmus maximus (L.) culture, in North-western
Spain. The disease affects the digestive tract, provokes severe catarrhal
enteritis, emaciation and high rates of mortality. The digestive parasitization
triggers a response with the coordinate participation of immune and
neuroendocrine systems through the action of peptides released by enteroendocrine
cells and present in nervous elements, acting as neuro-immune modulators. The
present study was designed to assess the response of the turbot neuroendocrine
system against E. scophthalmi infection. Immunohistochemical tests were applied
to sections of the gastrointestinal tract of uninfected and E. scophthalmi
infected turbot to characterize the presence of bombesin (BOM), glucagon (GLUC),
somatostatin (SOM), leu-enkephalin (LEU) and met-enkephalin (MET). The occurrence
of E. scophthalmi in the turbot gastrointestinal tract increased the number of
enteroendocrine cells immunoreactive to SOM, LEU and MET. On the other hand, BOM
and GLUC immunoreactive cells were less numerous in the gastrointestinal tract of
the parasitized turbot. Scarce immunoreactivity to BOM, GLUC and SOM was observed
in nerve fibres and neurons of the myenteric plexus of control and infected fish.
The results indicate that E. scophthalmi infection in turbot induced changes in
the neuroendocrine system, with the diminution of the anorexigenic peptides BOM
and GLUC; the increase of enkephalins, related to pro-inflammatory processes; and
the increase of SOM, which may cause inhibitory effects on the immune response,
constituting a compensatory mechanism to the exacerbated response observed in E.
scophthalmi-infected turbot.
PMID- 25134848
TI - Effects of emodin and vitamin E on the growth and crowding stress of Wuchang
bream (Megalobrama amblycephala).
AB - This study aimed to investigate the effects of dietary emodin, high-dose vitamin
E and their combination on the growth of Megalobrama amblycephala and its
resistance to acute crowding stress. The fish were randomly divided into four
groups: a control group fed with basal diet, and three treatment groups fed with
basal diet supplemented with 60 mg/kg emodin (the emodin group), 500 mg/kg
vitamin E (the vit E group), and 60 mg/kg emodin together with 500 mg/kg vitamin
E (the combination group). After 60 days, the fish were exposed to acute crowding
stress for 24 h. The results showed that the weight gain of the vit E group,
specific growth rate of the vit E group, total serum protein concentration (TP)
of the vit E group, serum lysozyme activity of the emodin group, serum superoxide
dismutase (SOD) activity of the emodin group, hepatic heat shock protein 70
(HSP70) levels of the vit E group and the emodin group, and serum alanine
aminotransferase (ALT) activity of the combination group significantly increased
while the weight gain and specific growth rate of the combination group
significantly decreased compared with the control group before stress. After
crowding stress, the vit E group had improved serum TP 12 h post-stress, hepatic
SOD activity 24 h post-stress, and hepatic HSP70 mRNA levels 12 and 24 h post
stress while the emodin group had enhanced serum SOD activity 12 and 24 h post
stress and hepatic HSP70 mRNA levels 12 and 24 h post-stress, as compared with
the control. However, the serum cortisol content of the three treatment groups 12
and 24 h post-stress, ALT activity in the vit E group and emodin group 24 h post
stress, and serum alkaline phosphatase and liver catalase activity in the
combination group 24 h post-stress were lower than those in the control group.
The cumulative mortality was lower in the emodin, vit E, and combination group
after Aeromonas hydrophila infection compared with the control group. Therefore,
dietary supplementation with 60 mg/kg emodin or 500 mg/kg vitamin E can improve
HSP70 mRNA levels and antioxidant capabilities, resistance to crowding stress,
and growth in M. amblycephala. However, the combination of emodin and vit E does
not have a synergistic effect in M. amblycephala.
PMID- 25134849
TI - Stability and retention of micronutrients in fortified rice prepared using
different cooking methods.
AB - Fortified rice holds great potential for bringing essential micronutrients to a
large part of the world population. However, it is unknown whether differences in
cooking methods or in production of rice premix affect the final amount of
micronutrient consumed. This paper presents a study that quantified the losses of
five different micronutrients (vitamin A, iron, zinc, folic acid, and vitamin
B12) in fortified rice that was produced using three different techniques (hot
extrusion, cold extrusion, and coating) during cooking and five different cooking
methods (absorption method with or without soaking, washing before cooking,
cooking in excess water, and frying rice before cooking). Fortified rice premix
from six different producers (two for each technique) was mixed with normal rice
in a 1:100 ratio. Each sample was prepared in triplicate, using the five
different cooking methods, and retention of iron, zinc, vitamin A, vitamin B12,
and folic acid was determined. It was found that the overall retention of iron,
zinc, vitamin B12, and folic acid was between 75% and 100% and was unaffected by
cooking method, while the retention of vitamin A was significantly affected by
cooking method, with retention ranging from 0% (excess water) to 80% (soaking),
depending on the cooking method and producer of the rice premix. No systematic
differences between the different production methods were observed. We conclude
that different cooking methods of rice as used in different regions of the world
do not lead to a major loss of most micronutrients, with the exception of vitamin
A. The factors involved in protecting vitamin A against losses during cooking
need to be identified. All production techniques of rice premix yielded similar
results, showing that coating is not inferior to extrusion techniques. Standard
overages (50%) for vitamin B12 and folic acid are too high.
PMID- 25134851
TI - Open versus endovascular repair of abdominal aortic aneurysm: Incidence of
cardiovascular events in 632 patients in a department of defense cohort over 6
year follow-up.
AB - BACKGROUND: Abdominal aortic aneurysm (AAA) is common with unacceptably high
rates of mortality and morbidity with unknown rates of complications after repair
in the Department of Defense (DoD). METHODS: All patients treated at a DOD or VA
clinic or medical facility with a diagnosis of AAA identified by ICD-9 code
search were identified by Patient Administration Systems and Biostatistics
Activity (PASBA) using the Standard Inpatient Data Record (SIDR) and Composite
Ambulatory Patient Encounter Record (CAPER) from January 2006 till December 2011.
The primary outcome was death, myocardial infarction (MI), stroke, and cardiac
arrhythmia between subjects who underwent endovascular aortic repair (EVAR) or
open aortic repair (OAR). RESULTS: A total of 8314 patients were screened to
identify 632 patients who underwent surgical repair of non-ruptured AAA. EVAR was
performed in 497 patients (78.6%) and OAR in 135 patients (21.4%). Mortality at
30 days was less common in EVAR patients (1.6% vs. 6.7%, p = 0.004), but was not
sustained (16.9% vs. 17.8%, p = 0.797). Mean survival free from mortality was not
different between the two groups (EVAR vs. OAR: 6.14 +/- 0.13 years vs. 6.11 +/-
0.22 years, p = 0.378). The composite endpoint of MI, stroke, arrhythmia, or
death was not different between groups at 30 days (EVAR vs. OAR: 12.9% vs. 14.1%,
p = 0.774) or in long-term follow-up population (EVAR vs. OAR: 40.6% vs. 31.9%, p
= 0.073) though there was a trend toward higher event rates in the EVAR. The
composite endpoint of MI, stroke, and arrhythmia occurred in 198 patients (31%).
CONCLUSION: EVAR was associated with lower 30-day mortality rates; however, this
benefit was not sustained in longer-term follow-up. There is no difference in the
rates of stroke, myocardial infarction, or cardiac arrhythmia at 30 days or in
long-term follow-up.
PMID- 25134850
TI - Production of the short peptide surfactant DAMP4 from glucose or sucrose in high
cell density cultures of Escherichia coli BL21(DE3).
AB - BACKGROUND: Peptides are increasingly used in industry as highly functional
materials. Bacterial production of recombinant peptides has the potential to
provide large amounts of renewable and low cost peptides, however, achieving high
product titers from Chemically Defined Media (CDM) supplemented with simple
sugars remains challenging. RESULTS: In this work, the short peptide surfactant,
DAMP4, was used as a model peptide to investigate production in Escherichia coli
BL21(DE3), a classical strain used for protein production. Under the same
fermentation conditions, switching production of DAMP4 from rich complex media to
CDM resulted in a reduction in yield that could be attributed to the reduction in
final cell density more so than a significant reduction in specific productivity.
To maximize product titer, cell density at induction was maximized using a fed
batch approach. In fed-batch DAMP4 product titer increased 9-fold compared to
batch, while maintaining 60% specific productivity. Under the fed-batch
conditions, the final product titer of DAMP4 reached more than 7 g/L which is the
highest titer of DAMP4 reported to date. To investigate production from sucrose,
sucrose metabolism was engineered into BL21(DE3) using a simple plasmid approach.
Using this strain, growth and DAMP4 production characteristics obtained from CDM
supplemented with sucrose were similar to those obtained when culturing the
parent strain on CDM supplemented with glucose. CONCLUSIONS: Production of a
model peptide was increased to several grams per liter using a CDM medium with
either glucose or sucrose feedstock. It is hoped that this work will contribute
cost reduction for production of designer peptide surfactants to facilitate their
commercial application.
PMID- 25134853
TI - Use of an ankle-foot orthosis improves aerobic capacity in subacute hemiparetic
stroke patients.
AB - OBJECTIVE: To investigate aerobic capacity with and without an ankle-foot
orthosis (AFO) in subacute hemiparetic stroke patients. DESIGN: Prospective
crossover intervention study. SETTING: Rehabilitation clinic in secondary care.
PATIENTS: Patients diagnosed with first-ever cerebral stroke involving the
cortical or subcortical area resulting in hemiparesis (n = 15, 8 men and 7 women;
average age, 62.1 years). METHODS: All subjects participated in 2 continuous,
symptom-limited, low-velocity graded treadmill exercise stress tests under 2
different conditions, namely, with and without an AFO. The rest interval between
tests was at least 48 hours. The order of exercise stress tests was randomized.
MAIN OUTCOME MEASUREMENTS: To assess cardiorespiratory responses, oxygen
consumption, heart rate, systolic blood pressure, diastolic blood pressure, rate
pressure product, and respiratory exchange ratio were measured continuously
throughout the test, and peak values were obtained. The rating of perceived
exertion was recorded immediately after each test. The percentage of the age
predicted maximal heart rate and total exercise duration were also measured. Gait
function was assessed by the Six-Minute Walk Test. RESULTS: Using an AFO
significantly increased peak oxygen consumption and Six-Minute Walk Test results.
Peak values of each of heart rate, systolic blood pressure, diastolic blood
pressure, rate-pressure product, and respiratory exchange ratio, rating of
perceived exertion, percentage of age-predicted maximal heart rate, and total
exercise duration were similar regardless of AFO use. CONCLUSIONS: Use of an AFO
may improve aerobic capacity in subacute hemiparetic stroke patients, and may
improve energy efficiency and gait endurance.
PMID- 25134854
TI - Successful treatment of athletic pubalgia in a lacrosse player with ultrasound
guided needle tenotomy and platelet-rich plasma injection: a case report.
AB - Athletic pubalgia is a syndrome of persistent groin pain due to chronic
repetitive trauma or stress involving the pelvic joints and many musculotendinous
structures that cross the anterior pelvis. As a result, the differential
diagnosis can be complex, but insertional tendinopathies are the most common.
This case report describes a novel approach to the treatment of distal rectus
abdominis tendinopathies with ultrasound-guided needle tenotomy and platelet-rich
plasma (PRP) injection. After injection, the patient returned to pain-free play
at his previous level of intensity. This suggests that PRP may be a useful
treatment for this diagnosis.
PMID- 25134852
TI - Improvements in lung function and height among cohorts of 6-year-olds with cystic
fibrosis from 1994 to 2012.
AB - OBJECTIVE: To characterize spirometry and height changes in cohorts of 6-year-old
children with cystic fibrosis (CF). STUDY DESIGN: Global Lung Initiative forced
expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC,
and the Centers for Disease Control and Prevention height-for-age (HFA) z-scores
were generated for 6-year-old children from the Cystic Fibrosis Foundation
Patient Registry each year between 1994 and 2012. Z-score mean differences were
analyzed by the t test, and time trends of means were analyzed by least squares
regression for all children and for subgroups of sex, F508del mutation genotype,
Medicaid insurance, and prenatal/newborn screening identification. Z-score
distributions were compared using the 2-sample Kolmogorov-Smirnov test. RESULTS:
A total of 11 670 children with CF were studied, of whom 50.5% were males, 50.2%
had the F508del/F508del genotype, and 46.6% were insured by Medicaid. Mean HFA,
FEV1, and FVC z-scores increased significantly over the period in the entire
cohort and in all subgroups (P < .001), but FEV1/FVC z-scores were below normal
and did not change significantly. In 2012, children identified by screening had
significantly higher mean HFA (P = .002), FEV1 (P < .001), and FVC (P < .001) z
scores compared with children not screened, with 90% of FVC and 71.4% of FEV1z
scores greater than predicted by the normal distribution. FEV1/FVC z-scores were
not different between the children who were and were not screened. CONCLUSION:
Consistent, significant increases in HFA, FEV1, and FVC occurred between 1994 and
2012, but FEV1/FVC, a measure of airway obstruction, did not change appreciably
during this period. FVC and FEV1z-score distributions suggest that normative
equation reference populations underpredict lung volumes of children with CF, but
the reasons for this remain unclear.
PMID- 25134855
TI - Drug loaded homogeneous electrospun PCL/gelatin hybrid nanofiber structures for
anti-infective tissue regeneration membranes.
AB - Infection is the major reason for guided tissue regeneration/guided bone
regeneration (GTR/GBR) membrane failure in clinical application. In this work, we
developed GTR/GBR membranes with localized drug delivery function to prevent
infection by electrospinning of poly(epsilon-caprolactone) (PCL) and gelatin
blended with metronidazole (MNA). Acetic acid (HAc) was introduced to improve the
miscibility of PCL and gelatin to fabricate homogeneous hybrid nanofiber
membranes. The effects of the addition of HAc and the MNA content (0, 1, 5, 10,
20, 30, and 40 wt.% of polymer) on the properties of the membranes were
investigated. The membranes showed good mechanical properties, appropriate
biodegradation rate and barrier function. The controlled and sustained release of
MNA from the membranes significantly prevented the colonization of anaerobic
bacteria. Cells could adhere to and proliferate on the membranes without
cytotoxicity until the MNA content reached 30%. Subcutaneous implantation in
rabbits for 8 months demonstrated that MNA-loaded membranes evoked a less severe
inflammatory response depending on the dose of MNA than bare membranes. The
biodegradation time of the membranes was appropriate for tissue regeneration.
These results indicated the potential for using MNA-loaded PCL/gelatin
electrospun membranes as anti-infective GTR/GBR membranes to optimize clinical
application of GTR/GBR strategies.
PMID- 25134856
TI - Feasibility and validity of telephone triage for adverse events during a
voluntary medical male circumcision campaign in Swaziland.
AB - BACKGROUND: Voluntary medical male circumcision (VMMC) reduces HIV acquisition
among heterosexual men by approximately 60%. VMMC is a surgical procedure and
some adverse events (AEs) are expected. Swaziland's Ministry of Health
established a toll-free hotline to provide general information about VMMC and to
manage post-operative clinical AEs through telephone triage. METHODS: We
retrospectively analyzed a dataset of telephone calls logged by the VMMC hotline
during a VMMC campaign. The objectives were to determine reasons clients called
the VMMC hotline and to ascertain the accuracy of telephone-based triage for VMMC
AEs. We then analyzed VMMC service delivery data that included date of surgery,
AE type and severity, as diagnosed by a VMMC clinician as part of routine post
operative follow-up. Both datasets were de-identified and did not contain any
personal identifiers. Proportions of AEs were calculated from the call data and
from VMMC service delivery data recorded by health facilities. Sensitivity
analyses were performed to assess the accuracy of phone-based triage compared to
clinically confirmed AEs. RESULTS: A total of 17,059 calls were registered by the
triage nurses from April to December 2011. Calls requesting VMMC education and
counseling totaled 12,492 (73.2%) and were most common. Triage nurses diagnosed
384 clients with 420 (2.5%) AEs. According to the predefined clinical algorithms,
all moderate and severe AEs (153) diagnosed through telephone-triage were
referred for clinical management at a health facility. Clinicians at the VMMC
sites diagnosed 341 (4.1%) total clients as having a mild (46.0%), moderate
(47.8%), or severe (6.2%) AE. Eighty-nine (26%) of the 341 clients who were
diagnosed with AEs by clinicians at a VMMC site had initially called the VMMC
hotline. The telephone-based triage system had a sensitivity of 69%, a positive
predictive value of 83%, and a negative predictive value of 48% for screening
moderate or severe AEs of all the AEs. CONCLUSIONS: The use of a telephone-based
triage system may be an appropriate first step to identify life-threatening and
urgent complications following VMMC surgery.
PMID- 25134858
TI - Factors predicting the development of pressure ulcers in an at-risk population
who receive standardized preventive care: secondary analyses of a multicentre
randomised controlled trial.
AB - AIMS: To identify predictive factors associated with the development of pressure
ulcers in patients at risk who receive standardized preventive care. BACKGROUND:
Numerous studies have examined factors that predict risk for pressure ulcer
development. Only a few studies identified risk factors associated with pressure
ulcer development in hospitalized patients receiving standardized preventive
care. DESIGN: Secondary analyses of data collected in a multicentre randomized
controlled trial. METHODS: The sample consisted of 610 consecutive patients at
risk for pressure ulcer development (Braden Score <17) receiving standardized
preventive care measures. Patient demographic information, data on skin and risk
assessment, medical history and diagnosis were collected during 26 months
(December 2007-January 2010). Predictive factors were identified using
multivariate statistics. RESULTS: Pressure ulcers in category II-IV were
significantly associated with non-blanchable erythema, urogenital disorders and
higher body temperature. Predictive factors significantly associated with
superficial pressure ulcers were admission to an internal medicine ward,
incontinence-associated dermatitis, non-blanchable erythema and a lower Braden
score. Superficial sacral pressure ulcers were significantly associated with
incontinence-associated dermatitis. CONCLUSIONS: Despite the standardized
preventive measures they received, hospitalized patients with non-blanchable
erythema, urogenital disorders and a higher body temperature were at increased
risk for developing pressure ulcers. RELEVANCE TO CLINICAL PRACTICE: Improved
identification of at-risk patients can be achieved by taking into account
specific predictive factors. Even if preventive measures are in place, continuous
assessment and tailoring of interventions is necessary in all patients at risk.
Daily skin observation can be used to continuously monitor the effectiveness of
the intervention.
PMID- 25134857
TI - The relationship between physician case volume and in-hospital mortality of
critically ill children with a diagnosis of pneumonia: a cross-sectional
observational analytical study.
AB - PURPOSE: The aim of this study is to examine the relationship between physician
case volume and the outcomes of critically ill children with pneumonia. MATERIALS
AND METHODS: This is a population-based cohort study analyzed data provided from
by the National Health Insurance Research Database of Taiwan, 2006-2009. Children
(aged 3 months to 17 years) having records of intensive care unit (ICU) admission
and a diagnosis of pneumonia were included. A total of 9754 critically ill
children and 1042 attending physicians were enrolled. The children were assigned
to 1 of 4 groups based on the physician's pneumonia case volume. RESULTS: The
patients in the very high case volume group had a significantly lower length of
hospital stay, in-hospital mortality rate, and hospitalization expenses, and a
significantly higher ratio of ICU to hospital stays than the other 3 groups
(P<.001). The probability of death tended to be lower when the physician's case
volume was higher. The risk-adjusted odds ratio for in-hospital mortality of very
high case volume group was 0.48 (95% confidence interval, 0.35-0.65; P<.001)
compared to low case volume group. CONCLUSIONS: A higher physician's pneumonia
case volume is associated with a lower length of hospital stay, lower in-hospital
mortality rate, and lower hospitalization expenses among critically ill children
with pneumonia.
PMID- 25134859
TI - Use of the donor lung after asphyxiation or drowning: effect on lung transplant
recipients.
AB - BACKGROUND: With the relative paucity of acceptable donors for lung
transplantation, criteria for extended donor consideration are being explored. We
sought to evaluate the suitability of donors whose cause of death was
asphyxiation or drowning (A/D) as a potential option to enlarge the donor pool.
METHODS: We queried the United Network for Organ Sharing (UNOS) Standard
Transplant Analysis and Research registry for lung transplantation from 1987 to
2010 to assess associations between cause of death and recipient survival using
the Kaplan-Meier method. To adjust for potential confounders, we used a Cox
proportional hazards model and a logistic regression model to evaluate incidence
of rejection within the first year. RESULTS: There were 18,250 adult primary lung
transplantations performed, with 309 A/D donors. There was no difference in
survival between groups (log-rank, p = 0.52). There were no differences in
demographics, length of stay, airway dehiscence, lung allocation score (LAS), or
ischemic time in univariate analysis (all p > 0.05). The A/D lung recipients had
fewer deaths from pulmonary causes (5.8% versus 9.5%; p = 0.02). Proportional
hazards analysis was significant for double lung transplantation (hazard ratio
[HR], 0.85; 95% confidence interval [CI], 0.8-0.9), height difference (HR, 1.002;
95% CI, 1.00-1.003), donor age greater than 50 years (HR, 0.89; 95% CI, 0.83
0.96), and recipient age greater than 55 years (HR, 0.8; 95% CI, 0.76-0.84). A/D
cause of death did not impact survival in multivariate analysis. CONCLUSIONS: A/D
as a donor cause of death was not associated with poor long-term survival or
incidence of rejection in the first year after transplantation. Donor cause of
death by A/D, when carefully evaluated and selected, should not automatically
exclude the organ from transplant consideration. These results provide important
justification for potentially broadening the donor pool safely.
PMID- 25134860
TI - Impact of perioperative glycemic control strategy on patient survival after
coronary bypass surgery.
AB - BACKGROUND: Glycemic control in the perioperative period decreases mortality and
morbidity, but data are scarce with regard to the effects of glucose control
approaches on survival. We assessed long-term survival in patients treated with 2
strategies of glucose control after first-time isolated coronary artery bypass
graft. METHODS: In a previously published trial, patients were prospectively
randomized to strict (90-120 mg/dL) or liberal (121-180 mg/dL) glucose control
protocols. The aim of this study was to assess long-term data on survival and
health-related quality of life based on the original prospective randomized study
population. RESULTS: No differences were found in cumulative survival between the
strict (95.5%) and liberal (93.5%) target range groups (log-rank = 0.32, p =
0.57) over a mean follow-up of 40.0 +/- 4.4 months. Physical health-related
quality of life significantly improved in all patients from baseline to 6 months
after surgery (F = 17.73, p < 0.001), and there were no differences in
improvement of health-related quality of life between the 2 target range groups
(F = 0.15, p = 0.70). CONCLUSIONS: These results support our previous findings
and indicate that a liberal glycemic control strategy after coronary artery
bypass leads to survival rates and improvements in health-related quality of life
that are similar to those achieved with a strict target range. In addition, the
liberal strategy is superior in glucose control and target range management.
PMID- 25134861
TI - Contemporary surgical approaches and outcomes in adults with Kommerell
diverticulum.
AB - BACKGROUND: Surgery in patients with Kommerell diverticulum (KD) is
controversial. Although the presence of symptoms is an accepted indication, the
KD itself may be a risk factor for dissection and rupture, although size criteria
for operation are undefined. METHODS: A retrospective review of 19 adult patients
who underwent surgical treatment of KD between March 2004 and June 2013 was
performed. Mean age was 48 years (range, 32 to 68 years). Fifteen patients were
female, 15 were symptomatic, and 13 had a right aortic arch. Sixteen patients
with aberrant subclavian artery underwent a two-stage procedure involving
subclavian-common carotid artery transposition or bypass followed by aortic
resection, including origin of the KD, with interposition graft reconstruction.
Aortic resection was performed with left heart bypass (n = 10) or deep
hypothermic circulatory arrest (n = 9). RESULTS: There were no deaths or strokes.
Complications after aberrant subclavian artery revascularization were transient
ptosis (n = 3), graft occlusion (n = 1), recurrent laryngeal nerve injury (n =
1),phrenic nerve injury (n = 1), and reintubation (n = 1). Complications after
aortic resection were intraoperative type A dissection (n = 1), phrenic nerve
injury (n = 1), chylothorax (n = 1), and transient neurologic dysfunction (n =
1). Mean hospital stay after aberrant subclavian artery revascularization was 2
+/- 2 days and after aortic resection, 6.4 +/- 2.4 days. Of 18 available
pathology specimens, all 18 showed medial degeneration. Mean follow-up was 3.3
years. CONCLUSIONS: This is the largest reported single-center experience with
the surgical management of KD in adults, verifying its safety and efficacy. The
high percentage of KD with medial degeneration suggests asymptomatic patients
with an enlarged KD also may benefit from resection.
PMID- 25134862
TI - Surgical treatment of metachronous second primary lung cancer.
AB - BACKGROUND: Many studies have demonstrated that patients with metachronous second
primary lung cancer (MSPLC) benefit from surgery. Owing to the lack of uniform
criteria and prospective randomized trials, the extent of resection remains
controversial, and prognostic factors are still not fully clear. The present
study aimed to assess surgical treatment of MSPLC and identify prognostic factors
of outcome. METHODS: This retrospective analysis included 143 patients who
underwent surgical resection of MSPLC in our department from January 2006 to
December 2011. Predictors of postoperative complications were analyzed with the
binary logistic regression method. Survival was analyzed with Kaplan-Meier and
Cox regression methods. RESULTS: Operative mortality was 1.4%, and the
complication rate was 34.3%. Age more than 70 years was an independent risk
factor for postoperative complications. The overall 5-year survival after
resection of MSPLC was 54.5%. TNM stage II or higher (p = 0.025), 20 or more pack
years of smoking (p = 0.037), and tumor size greater than 2 cm (p = 0.033) were
independent negative prognostic factors for survival. For stage I disease,
completion pneumonectomy had a lower 5-year survival rate than others, 44.8% and
65.9, respectively (p = 0.039); lobectomy and sublobar resection have a 5-year
survival of 77.1% and 56.7%, respectively (p = 0.203). CONCLUSIONS: Surgical
treatment of MSPLC is safe and effective. TNM stage I, tumor size 2 cm or less,
or less than 20 pack-years smoking are predictors of improved survival. Sublobar
resection is acceptable. For stage I disease, lobectomy tends to be associated
with better survival than sublobar resection, although the difference is not
significant, and completion pneumonectomy is not recommended. Long-term follow-up
is necessary even after curative resection of lung cancer.
PMID- 25134863
TI - Predictors of early recurrence for node-negative t1 to t2b non-small cell lung
cancer.
AB - BACKGROUND: Recurrence develops in nearly one-third of patients who undergo
complete resection for non-small cell lung cancer (NSCLC). We sought to identify
predictors of early recurrence (<2 years) in node-negative T1 to T2b NSCLC.
METHODS: We used a 10-year (1999 to 2008) single-institution retrospective review
of a prospectively maintained lung cancer database. Exclusion criteria included
carcinoid, adenocarcinoma in situ, and minimally invasive adenocarcinoma
histologies, and any induction therapy. Patient demographics, clinical, and
pathologic variables were analyzed. Recurrence was confirmed histologically in 86
patients (85%) or radiographically in 16 (15%). Univariable and multivariable
logistic regression (C statistic = 0.7) and Cox proportional hazards analyses
were performed (p < 0.05 is significant). RESULTS: An R0 resection of a node
negative T1 to T2b NSCLC was performed in 532 patients. Procedures included
lobectomy in 436, segmentectomy in 47, and wedge resection in 49. Recurrence was
present in 102 patients (19%) and was locoregional in 33 (32%), distant in 40
(39%), and multisite in 29 (29%). T size, tumor histology, tumor grade, smoking
status, maximum standardized uptake value, and albumin were not associated with
recurrence. Multivariable predictors of recurrence were lymphovascular invasion
(odds ratio, 2.48), sublobar resection (odds ratio, 2.37), and age (odds ratio,
0.96). Recurrence was independently associated with lung cancer-specific death
(relative risk, 11.78; 95% confidence interval, 5.46 to 25.36; p < 0.001) and
overall mortality (relative risk, 1.27; 95% confidence interval, 1.16 to 1.39, p
< 0.001). CONCLUSIONS: We demonstrate a 19% early recurrence rate in R0 resected
node-negative T1 to T2b NSCLC. The identification of unique predictors of
recurrence is an important step toward defining a patient population that may
benefit from adjuvant therapy.
PMID- 25134864
TI - Significance of low peak Doppler velocity in the proximal sano conduit in
hypoplastic left heart syndrome.
AB - BACKGROUND: The Sano modification of the Norwood operation is a well-established
first step palliation for hypoplastic left heart syndrome (HLHS). Theoretically,
the first point of resistance to pulmonary flow should be in the proximal Sano,
generating high Doppler flow velocity. Paradoxically, however, some patients have
low gradients in the proximal Sano conduit. The objective of this study was to
determine the hemodynamic and anatomic significance of low proximal Sano Doppler
flow velocity and its clinical implications. METHODS: Doppler-derived peak
gradients in the proximal Sano conduits were measured in HLHS patients after
Norwood-Sano surgery over a 4-year period and confirmed by cardiac
catheterization within 2 to 4 weeks. Clinical outcomes of patients with proximal
Sano gradients of 30 mm Hg or less (group 1) were compared with patients whose
gradient was greater than 30 mm Hg (group 2). RESULTS: Of the 53 patients, 21
(40%) belonged to group 1. Patients in group 1 had smaller ostial right and left
pulmonary artery (PA) diameter (3.2 +/- 1.2 mm versus 4.5 +/- 1.8 mm, p = 0.03;
and 3.4 +/- 1.2 mm versus 5.6 +/- 2.1 mm, p = 0.01) when compared with patients
in group 2. Patients (7 of 10) who needed either balloon angioplasty of a distal
Sano or proximal branch PA were from group 1 (p = 0.01). Patients in group 1 had
higher rates of unintended PA interventions (33% versus 9%) and complications
(48% versus 16%) compared with group 2. CONCLUSIONS: Low peak Doppler flow
velocity in the proximal Sano correlates with the presence of either distal Sano
stenosis or proximal branch PA stenosis. These patients require close follow-up
in the interstage period and may need earlier intervention.
PMID- 25134865
TI - Cost effectiveness of teratology counseling - the Motherisk experience.
AB - BACKGROUND: While the benefits of evidence-based counseling to large numbers of
women and physicians are intuitively evident, there is an urgent need to document
that teratology counseling, in addition to improving the quality of life of women
and families, also leads to cost saving. The objective of the present study was
to calculate the cost effectiveness of the Motherisk Program, a large teratology
information and counseling service at The Hospital for Sick Children and the
University of Toronto. METHODS: We analyzed data from the Motherisk Program on
its 2012 activities in two domains: 1) Calculation of cost-saving in preventing
unjustified pregnancy terminations; and 2) prevention of major birth defects.
Cost of pregnancy termination and lifelong cost of specific birth defects were
identified from primary literature and prorated for cost of living for the year
2013. RESULTS: Prevention of 255 pregnancy terminations per year led to cost
savings of $516,630. The total estimated number of major malformations prevented
by Motherisk counseling in 2012 was 8.41 cases at a total estimated cost of
$9,032,492. CONCLUSIONS: With an estimated minimum annual prevention of 8 major
malformations, and numerous unnecessary terminations of otherwise- wanted
pregnancies, a cost saving of $10 million can be calculated. In 2013 the
operating budget of Motherisk counseling totaled $640,000. Even based on the
narrow range of activities for which we calculated cost, this service is highly
cost- effective. Because most teratology counseling services are operating in a
very similar method to Motherisk, it is fair to assume that these results,
although dependent on the size of the service, are generalizable to other
countries.
PMID- 25134866
TI - The plant decapeptide OSIP108 prevents copper-induced toxicity in various models
for Wilson disease.
AB - BACKGROUND: Wilson disease (WD) is caused by accumulation of excess copper (Cu)
due to a mutation in the gene encoding the liver Cu transporter ATP7B, and is
characterized by acute liver failure or cirrhosis and neuronal cell death. We
investigated the effect of OSIP108, a plant derived decapeptide that prevents Cu
induced apoptosis in yeast and human cells, on Cu-induced toxicity in various
mammalian in vitro models relevant for WD and in a Cu-toxicity zebrafish larvae
model applicable to WD. METHODS: The effect of OSIP108 was evaluated on viability
of various cell lines in the presence of excess Cu, on liver morphology of a Cu
treated zebrafish larvae strain that expresses a fluorescent reporter in
hepatocytes, and on oxidative stress levels in wild type AB zebrafish larvae.
RESULTS: OSIP108 increased not only viability of Cu-treated CHO cells
transgenically expressing ATP7B and the common WD-causing mutant ATP7B(H1069Q),
but also viability of Cu-treated human glioblastoma U87 cells. Aberrancies in
liver morphology of Cu-treated zebrafish larvae were observed, which were further
confirmed as Cu-induced hepatotoxicity by liver histology. Injections of OSIP108
into Cu-treated zebrafish larvae significantly increased the amount of larvae
with normal liver morphology and decreased Cu-induced production of reactive
oxygen species. CONCLUSIONS: OSIP108 prevents Cu-induced toxicity in in vitro
models and in a Cu-toxicity zebrafish larvae model applicable to WD. GENERAL
SIGNIFICANCE: All the above data indicate the potential of OSIP108 as a drug lead
for further development as a novel WD treatment.
PMID- 25134867
TI - Psychopharmacology.
AB - Primary care providers (PCPs) are frequently responsible for the pharmacologic
management of mood disorders, and the PCP is often an important member of the
clinical team in the management of bipolar disorder and schizophrenia. Not only
is a good understanding of psychopharmacology important for the effective
treatment of psychiatric disease, it is also necessary for patient safety.
Clinicians should understand the side effects and the medication interactions
associated with psychotropic medications. This article reviews mechanisms of
action, indications, dosing, side effects, medication interactions, and general
management considerations for common medications used to treat psychiatric
conditions encountered in the primary care setting.
PMID- 25134868
TI - Office-based screening of common psychiatric conditions.
AB - Depression and anxiety disorders are common conditions with significant
morbidity. Many screening tools of varying length have been well validated for
these conditions in the office-based setting. Novel instruments, including
Internet-based and computerized adaptive testing, may be promising tools in the
future. The best evidence for cost-effectiveness currently is for screening of
major depression linked with the collaborative care model for treatment. Data are
not conclusive regarding comparative cost-effectiveness of screening for multiple
conditions at once or for other conditions. This article reviews screening tools
for depression and anxiety disorders in the ambulatory setting.
PMID- 25134869
TI - Major depression.
AB - Major depression is a common, disabling condition seen frequently in primary care
practices. Non-psychiatrist ambulatory providers are increasingly responsible for
diagnosing, and primarily managing patients suffering from major depressive
disorder (MDD). The goal of this review is to help primary care providers to
understand the natural history of MDD, identify practical tools for screening,
and a thoughtful approach to management. Clinically challenging topics like co
morbid conditions, treatment resistant depression and pharmacotherapy selection
with consideration to side effects and medication interactions, are also covered.
PMID- 25134870
TI - Anxiety disorders in primary care.
AB - Anxiety disorders are the most common psychiatric condition presenting to primary
care practitioners. Yet they can be easily overlooked or misdiagnosed. Patients
that struggle with anxiety disorders are more likely to seek treatment from
primary care providers than mental health specialists. Given the costs in terms
of debilitation and associated financial burden, and increased risk of suicide,
the identification and successful treatment of anxiety is imperative. By means of
clinical acumen and the use of screening tools, the provider can develop
expertise in recognition and effective treatment of anxiety disorders.
PMID- 25134871
TI - Diagnosis and management of bipolar disorder in primary care: a DSM-5 update.
AB - This review discusses the diagnosis and detection of bipolar disorder in the
primary care population with recent changes introduced by Diagnostic and
Statistical Manual of Mental Disorders, Fifth Edition and the pharmacotherapy and
psychosocial management of this psychiatric condition.
PMID- 25134872
TI - Borderline personality disorder in the primary care setting.
AB - Borderline personality disorder is estimated to be present in approximately 6% of
outpatient primary care settings. However, the time and energy spent on this
population can greatly exceed what primary care doctors are able to spend. This
article gives an overview of borderline personality disorder, including the
clinical characteristics, epidemiology, and comorbidities, as well as
pharmacologic and most important behavioral management. It is our hope that, with
improved understanding of the disorder and skills for managing this population,
caring for patients with the disorder can be more satisfying and less taxing for
both primary care doctors and their patients.
PMID- 25134873
TI - Seasonal affective disorder, grief reaction, and adjustment disorder.
AB - Seasonal affective disorder is a subtype of other affective disorders. The most
studied treatment is light therapy, although second-generation antidepressants
are also an option. Grief reactions are normal for patients experiencing loss,
and primary care providers (PCPs) should be aware of both the expected course of
grief and the more severe symptoms that indicate complex grief. Adjustment
disorder is a time-limited abnormal response to a stressor. PCPs can manage
patients with adjustment disorder by arranging counseling, screening for
suicidality, assessing for substance abuse, and ruling out other psychiatric
diagnoses. At present there are no reliable data to suggest medication
management.
PMID- 25134874
TI - Approach to the patient with multiple somatic symptoms.
AB - Primary care providers play a crucial role in the recognition and appropriate
treatment of patients with multiple somatic complaints. Both the number of
somatic symptoms and the persistence of symptoms are associated with co-occurring
depression or anxiety disorders. It can be challenging to simultaneously address
possible medical causes for physical symptoms while also considering an
associated psychiatric diagnosis. In this article, strategies to improve the care
and outcomes among these patients are described, including collaboration,
education about the interaction between psychosocial stressors and somatic
symptoms, regularly scheduled visits, focus on improving functional status, and
evidence-based treatment of depression and anxiety.
PMID- 25134875
TI - Addiction disorders.
AB - Substance use disorders are common in primary care settings, but detection,
assessment, and management are seldom undertaken. Substantial evidence supports
alcohol screening and brief intervention for risky drinking, and pharmacotherapy
is effective for alcohol use disorders. Substance use disorders can complicate
the management of chronic noncancer pain, making routine monitoring and
assessment for substance use disorders an important aspect of long-term opioid
prescribing. Patients with opioid use disorders can be effectively treated with
methadone in opioid treatment programs or with buprenorphine in the primary care
setting.
PMID- 25134876
TI - Psychiatric disorders and sleep issues.
AB - Sleep issues are common in people with psychiatric disorders, and the interaction
is complex. Sleep disorders, particularly insomnia, can precede and predispose to
psychiatric disorders, can be comorbid with and exacerbate psychiatric disorders,
and can occur as part of psychiatric disorders. Sleep disorders can mimic
psychiatric disorders or result from medication given for psychiatric disorders.
Impairment of sleep and of mental health may be different manifestations of the
same underlying neurobiological processes. For the primary care physician, key
tools include recognition of potential sleep effects of psychiatric medications
and familiarity with treatment approaches for insomnia in depression and anxiety.
PMID- 25134877
TI - Psychiatric care of the older adult: an overview for primary care.
AB - As the population ages, primary care providers will be frequently called on to
manage psychiatric disorders suffered by their older patients. This overview of
delirium, dementia, depression, and alcohol and substance misuse highlights the
common presentations and suggests initial approaches to treatment. The challenges
facing caregivers are also discussed.
PMID- 25134880
TI - Foreword. Psychiatric diagnosis and management in primary care.
PMID- 25134879
TI - Medical conditions with neuropsychiatric manifestations.
AB - Medical disease sometimes affects patients through neuropsychiatric
manifestations. When neuropsychiatric symptoms are predominant, identifying
medical disease early in the illness course is imperative because many of these
conditions are reversible with appropriate treatment. A high index of suspicion
is required on the part of clinicians, particularly when patients also present
with physical signs or unexplained symptoms that might suggest a broader,
systemic process. The processes that most commonly cause neuropsychiatric
symptoms include infectious, autoimmune, endocrinologic, metabolic, and
neoplastic diseases. This article focuses on the most common of these conditions,
and conditions for which early diagnosis and treatment are particularly
important.
PMID- 25134878
TI - Primary care for adults on the autism spectrum.
AB - Autism spectrum disorder (ASD) is defined by differences in social communication
and restricted, repetitive patterns of behavior, interests, or activities. Skills
and challenges can change depending on environmental stimuli, supports, and
stressors. Quality of life can be improved by the use of accommodations,
assistive technologies, therapies to improve adaptive function or communication,
caregiver training, acceptance, access, and inclusion. This article focuses on
the identification of ASD in adults, referrals for services, the recognition of
associated conditions, strategies and accommodations to facilitate effective
primary care services, and ethical issues related to caring for autistic adults.
PMID- 25134881
TI - Preface. Psychiatric diagnosis and management in primary care.
PMID- 25134882
TI - Understanding decreased fertility in women carriers of the FMR1 premutation: a
possible mechanism for Fragile X-Associated Primary Ovarian Insufficiency
(FXPOI).
AB - Fragile X syndrome (FXS) and its associated disorders are caused by the expansion
of the CGG repeat in the 5' untranslated region of the fragile X mental
retardation 1 gene (FMR1). The full mutation, defined as >200 cytosine-guanine
guanine (CGG) triplet repeats, causes FXS. Individuals with 55-199 CGG repeats,
classified as premutation carriers, are affected by two distinct disorders
depending on their premutation status. Disorders associated with premutation
carriers include: Fragile X-associated Tremor Ataxia Syndrome (FXTAS) and Fragile
X-associated Primary Ovarian Insufficiency (FXPOI). The molecular similarities of
FXTAS and FXPOI (e.g. overabundance of FMR1 transcript and intranuclear
inclusions) suggest that similar molecular mechanisms underlie both FXTAS and
FXPOI. The current hypothesis describes the underlying mechanism for FXTAS as an
mRNA gain-of-function mutation, however the underlying mechanism for FXPOI
remains unresolved. New data suggests that repeat associated non-AUG (RAN)
translation could underlie FXPOI.
PMID- 25134883
TI - Medical resident choices of electronic drug information resources.
AB - OBJECTIVE: To determine medical residents' day-to-day use of drug information
resources since their choices of these resources, when faced with common
questions, are unknown. METHODS: An online survey including simulated drug
information questions was administered to 146 medical residents in the Department
of General Internal Medicine during July 2012. Residents were given a wide range
of choices in drug information resources to answer these questions and were
instructed to select what they would choose in actual practice. A score was
assigned to each resource corresponding to a "best," "intermediate," or "not
good" choice. RESULTS: Seventy-three respondents completed the survey and results
were analyzed for statistical significance. Fifty-seven percent of respondents
reported receiving no formal training regarding drug information. Statistical
analyses revealed there were no significant differences in performance based on
postgraduate year (P = .43) or extent of prior training (P = .45). Individual
question responses revealed a generally infrequent selection of "best" choices.
Less than 10% of the respondents chose the "best" answer for drug information
questions related to drug interactions, herbal supplements, adverse events, and
medication identification. CONCLUSION: Further training in drug information
resource selection is warranted in the medical residency program to increase the
frequency of use of higher quality resources.
PMID- 25134884
TI - Drug-induced immune thrombocytopenia.
AB - Thrombocytopenia is commonly seen in laboratory findings, especially in
critically ill patients. Although the incidence is rare, drug-induced immune
thrombocytopenia (DITP) is a serious complication that is often overlooked as a
cause of thrombocytopenia. Over the last century, extensive research and data
collection have been done in an attempt to better characterize DITP. Heparin
induced thrombocytopenia is the most common DITP and has distinct pathogenesis,
diagnosis, and treatment options. However, other offending medications are less
well known and have triggered many questions and constant search for answers.
This review will discuss both drug-induced immune-mediated and nonimmune-mediated
thrombocytopenias, with a focus on immune-mediated processes. Thrombocytopenia
caused by chemotherapy will not be discussed in this article.
PMID- 25134885
TI - Measuring the impact of information skills training: a survey of health libraries
in England.
AB - BACKGROUND: The lack of robust research measuring the impact of NHS based
information skills training prompted the West Midlands Regional Trainers' Forum
to conduct a post-training survey. METHODS: This is a multi-centred study which
collected data from over 60 separate organisations. Survey questionnaires were
completed by learners a few weeks after the training event. RESULTS: Five hundred
and thirty-four responses were received. 82% of information skills training
recipients indicated that they had implemented learning or changed practice as a
result of the training. 70% of recipients indicated there had been an impact on
patient care. DISCUSSION: The beneficial results from information skills training
manifest in a multitude of ways. The results of this study indicate that the
learning from information skills training is being used to reduce problems and
address the key issues in modern health care. CONCLUSION: The results clearly
demonstrate the value of information skills training and its beneficial impact on
patient care, lifelong learning and other key NHS functions. This study shows
information skills training as an important activity which supports the
information literacy agenda, and has a positive impact across the four key
functions of library and knowledge services within the NHS.
PMID- 25134888
TI - Prevalence of intestinal parasitic infections among communities living in
different habitats and its comparison with one hundred and one studies conducted
over the past 42 years (1970 to 2013) in Malaysia.
AB - Intestinal parasitic infections are among the most common diseases affecting
mankind causing major public health problems to billions of people living in
developing countries. The aim of this study is to determine the prevalence of
intestinal parasites in various communities residing in different habitats in
Malaysia and compare the findings with 101 studies conducted over the past 42
years (1970-2013). A cross-sectional study design was conducted with the aid of a
questionnaire to collect relevant information about the study population. Faecal
samples were examined using the direct smear and formal ether sedimentation
techniques. A total of 342 children were examined amongst whom 24.6% were
positive for intestinal parasitic infections. Results showed that 32.3% of rural
children, 20.6% of urban squatters and 5.4% of children from flats were positive
for one or more parasites. The most common parasite encountered was Trichuris
trichiura (20.2%) followed by Ascaris lumbricoides (10.5%) and hookworm (6.7%).
No case of hookworm was reported in urban children whereas 12.2% of rural
children were positive. The most common protozoan parasite detected was Entamoeba
coli (3.2%) followed by Giardia intestinalis (1.8%), Entamoeba histolytica (1.8%)
and Blastocystis hominis (1.2%). Nearly one-fifth (18.4%) of the children had
single infection followed by double (12.0%) and triple infections (1.2%). Orang
Asli (indigenous) children (44.3%) had the highest infection rate followed by
Indians (20.2%), Malays (14.0%) and Chinese (11.9%). Twenty-eight studies carried
out on plantation communities with regards to intestinal parasitic infections in
Malaysia from 1970 to 2013 showed a steady decline in the prevalence rate ranging
from 95.0% in the seventies to 37.0 % in 2012. Intestinal parasitic infections
were more common in Orang Asli communities with prevalence ranging from over 90%
in the seventies and fluctuating below 70% in most studies between 2000 to 2013
except for two studies that showed a prevalence of 98.2% and 100%. The prevalence
rate among urban squatters, urban residents and those living in flats showed
dramatic decrease in prevalence rate.
PMID- 25134889
TI - Coexistence of Philodina roseola (Rotifera: Bdelloidea) with larvae of Aedes
aegypti in India.
AB - The vector mosquitoes, Aedes aegypti and Aedes albopictus of dengue and
Chikungunya fever are closely associated with human habitations and adapted to
feed on human blood. They undergo larval and pupal development in natural and
artificial freshwater collections in the urban and peri-urban environment.
Although reports are available about the feeding behaviour of the thriving
mosquito larvae, much information is still required to understand the successful
survival of Aedes mosquitoes in small and temporary water collections. This study
was undertaken to determine the co-existence and prevalence of Philodina roseola
and other Bdelloid rotifers in the container habitats of Ae. aegypti mosquitoes.
The investigation was conducted in 43 villages which belong to four districts in
South India, affected by the epidemic of either dengue or Chikungunya fever. A
total of 2093 houses and 12980 containers were examined for Aedes breeding and
those containers with Aedes larvae were chosen for further investigation. The
investigation showed that, the P. roseola was found associated in 502 (98.2%)
containers, P. roseola along with other Philodina sp. in 126 containers (25%) and
P. roseola along with other Philodina sp. and other Bdelloid rotifers found in 93
containers (19%). Since the members of the genus Philodina can survive
desiccation, reproduce by parthenogenesis, can be transported by wind easily and
more importantly, it can incorporate the genome of other organisms including
viruses, understanding the co-existence and relationship of Philodina sp. with
Aedes larvae would be helpful in the control of Aedes breeding and the control
measures can be designed keeping the association of Bdelloids with Aedes in mind.
PMID- 25134886
TI - Key informant interviews with coordinators of special events conducted to
increase cancer screening in the United States.
AB - Special events such as health fairs, cultural festivals and charity runs are
commonly employed in the community to increase cancer screening; however, little
is known about their effectiveness. The purpose of this study is to assess the
activities, screening outcomes, barriers and recommendations of special events to
increase breast, cervical and colorectal cancer screening. In-depth interviews
were conducted nationally with 51 coordinators of events in June to September
2012. Health fairs and screening days were the most common events conducted,
primarily for breast cancer education. Goals were to increase awareness of cancer
screening and reach special populations. Evidence-based Community Guide
strategies to increase cancer screening employed were: small media, reducing
structural barriers, one-on-one education or group education. For each event that
provided screening on-site or through referral, a mean of 35 breast, 28 cervical
and 19 colorectal cancer screenings were reported. Coordinators made
recommendations for further evaluation of special events, and most plan to
conduct another special event. These data are novel and provide baseline
documentation of activities and recommendations for a commonly used community
based cancer screening intervention that lacks evidence of effectiveness.
Additional research to better understand the use of special events for increasing
cancer screening is warranted.
PMID- 25134887
TI - Bilingual children with primary language impairment: 3 months after treatment.
AB - BACKGROUND: Evidence on the treatment effectiveness for bilingual children with
primary language impairment (PLI) is needed to advance both theory and clinical
practice. Of key interest is whether treatment effects are maintained following
the completion of short-term intense treatments. AIMS: To investigate change in
select language and cognitive skills in Spanish-English bilingual children with
PLI 3 months after children have completed one of three experimental treatment
conditions. There are two main study aims. First, to determine if skills in
Spanish, English and cognitive processing decline, improve or are maintained
after treatment has been completed. Second, to determine if differential rates of
change are a function of the type of treatment children received. METHODS &
PROCEDURES: Participants were 48 children, aged 5:6-11:3, who spoke Spanish and
English and were diagnosed with moderate to severe PLI. Participants received 6
weeks of treatment focused on English only (EO), bilingual skills in Spanish and
English (BI) or nonlinguistic cognitive processing (NCP). Treatment effects
reported in a previous study were determined by comparing pre- and post-treatment
performance on a variety of language and cognitive measures. Here we re
administered each measure 3 months after completion of the experimental
treatments. Hierarchical linear models were calculated for each measure using pre
, post- and follow-up testing scores to estimate change trajectories and compare
outcomes between treatment conditions. OUTCOMES & RESULTS: Participants in all
three treatment conditions either maintained skills or showed improvement even
after treatment was discontinued for 3 months. Main findings included (1)
comparable, positive rates of change on all English language outcomes for EO and
BI conditions; (2) maintenance of Spanish language skills, and (3) modest
improvements in NCP following the discontinuation of treatment. CONCLUSIONS &
IMPLICATIONS: This study is the first to examine longer-term treatment effects
for bilingual school-age children with PLI. Differences in rates of change
between languages and between treatment conditions are discussed in terms of
social and cognitive processes that impact children's language systems. The main
findings have at least two implications for clinical practice: (1) therapy that
emphasizes focused practice in language and cognitive processing skills may
promote gains in children's language learning abilities; and (2) bilingual
treatment does not detract from outcomes in English, the language of the majority
community for study participants.
PMID- 25134891
TI - Measuring impact on filarial infection status in a community study: role of
coverage of mass drug administration (MDA).
AB - Lymphatic filariasis is still endemic in many parts of India. The main strategy
to implement mass drug administration with DEC and albendazole was added in 2006
to ensure increased impact on the microfilaria (mf) rate in the community.
However, the effective coverage remained low in the community leading to lower
than desired impact on the parasite population in human. This paper presents the
dynamics of participation in annual repeated rounds of mass drug administration
in some villages of Kanpur Nagar district in Uttar Pradesh and its impact over
the infection rate. It is revealed that after 6 annual rounds of MDA, mf rate
could only be reduced by 17.3% in population subgroups who participated only once
in comparison to 88% in those who participated in 6 or all annual rounds.
PMID- 25134890
TI - Prevalence and genotyping of Cryptosporidium in stool samples collected from
children in Taif City (Saudi Arabia).
AB - This study was conducted to estimate the frequency of Cryptosporidium infections
in Taif (Saudi Arabia). Stool samples from children under 10 years by modified
Ziehl-Neelson staining and two PCR techniques were used for genotyping
experiments. The microscopic examination showed that, eleven samples were
positive for presence of Cryptosporidium. With 11 of 100 samples, DNA extraction
and subsequent genotyping was successful. By means of RAPD technique, the genetic
similarity among the collected isolates was 55%. The 18S rRNA gene sequences
confirmed that all Cryptosporidium-isolates belonged to Cryptosporidium parvum.
In comparison with reference strains from different species of Cryptosporidium
species from GenBank, all collected isolates belonged to Cryptosporidium hominis
and C. parvum clade. The fact that only human genotypes were detected suggests
that cryptosporidiosis must primarily be considered as a non zoonotic disease in
Taif region.
PMID- 25134892
TI - Epidemiology of blood parasitic infections in the urban rat population in
peninsular Malaysia.
AB - A total of 719 wild rats were captured from four localities representing the west
(Kuala Lumpur), east (Kuantan), north (Georgetown) and south (Malacca) to
determine the diversity of blood protozoan from the urban wild rat population in
peninsular Malaysia. Five rat species were recovered with Rattus rattus diardii
being the most dominant species, followed by Rattus norvegicus, Rattus exulans,
Rattus annandalei and Rattus argentiventer. Two blood protozoan species were
found infecting the rodent population namely, Plasmodium sp. (42.1%) and
Trypanosoma lewisi (25.0%). This study reports the presence of Plasmodium sp. for
the first time in the rodent population in Malaysia. Two main intrinsic factors
were identified affecting the parasitic infections. Trypanosoma lewisi infections
were influenced by host age and sex with infections observed higher in male and
juvenile rats meanwhile Plasmodium sp. infections were observed almost similar in
both sexes. However, infections were higher in sub-adult rats.
PMID- 25134893
TI - Multiple resistance of Culex vishnui Theobald against four major classes of
insecticides in an agricultural area in Sekinchan, Selangor, Malaysia.
AB - The resistance status of riceland Culex vishnui against four major groups of
insecticides (i.e., organochlorines, carbamates, organophosphates and
pyrethroids) was investigated. Biochemical assays (ESTalpha, ESTbeta, MFO and
GST) were also conducted to detect the resistance levels. Throughout a 12-month
study period, multiple insecticide resistance was observed in both larvae and
adult Cx vishnui. Culex vishnui larvae exhibited low resistance against
malathion, temephos and permethrin with resistance ratio (RR) values < 5. In
adult bioassay, Cx. vishnui were highly resistant against all tested adulticides
with 24h post-treatment mortality < 70%. Correlations between permethrin and
malathion resistance, as well as between deltamethrin and cyfluthrin resistance
were found in Cx. vishnui. The results indicated that mixed function oxidases
activity of Cx. vishnui was the highest compared to ESTalpha, ESTbeta and GST.
Spearman rank-order analysis showed that ESTalpha, ESTbeta and GST were involved
in multiple resistances in Cx. vishnui. The findings of this study established a
baseline of insecticide susceptibility and revealed the effects of agricultural
insecticide pressure on the vectors of Japanese encephalitis in Malaysia.
PMID- 25134894
TI - First survey of helminths in adult goats in Hunan Province, China.
AB - The objective of the present survey was to reveal the prevalence of helminths in
adult goats in Hunan Province, the People's Republic of China. From July 2010
through February 2013, a total of 479 goats slaughtered in local abattoirs and
markets were examined for the presence of helminths using a helminthological
approach. Eighty-six percent of the examined goats were infected with at least
one species of helminths. In total, 15 genera of helminths were found
representing 2 phyla, 3 classes, 5 orders, and 11 families. Oesophago-stomum,
Ostertagia and Haemonchus were the most prevailing nematode genera, Eurytrema was
the predominant trematode genus detected, whereas the infection of adult goats
with cestodes was not common, with Cysticercus tenuicollis being the most common
genus. The worm burdens showed obvious seasonal variation in that nematodes and
cestodes were abundant in summer and winter, and the trematodes peaked in winter,
which was consistent with the seasonal precipitation of Hunan Province. The
geographical distribution of helminths in goats ascended with altitude. Goats in
the mountainous areas were more severely infected with helminths than goats in
the hilly areas, whereas infection of goats with helminths was much less in the
lake areas. The present investigation highlights the high prevalence of helminths
in adult goats in Hunan Province, China, which provides baseline data for
assessing the effectiveness of future prevention and controlling measures against
helminth infection in adult goats in this province and elsewhere.
PMID- 25134895
TI - Bleeding outcome during a dengue outbreak in 2005 in the East-coast region of
Peninsular Malaysia: a prospective study.
AB - During a dengue outbreak in 2005 in the East-coast region of Peninsular Malaysia,
one of the worst hit areas in the country at that time, we undertook a
prospective study. We aimed to describe the bleeding outcome and changes in the
liver and hematologic profiles that were associated with major bleeding outcome
during the outbreak. All suspected cases of dengue admitted into the only
referral hospital in the region during the outbreak were screened for WHO 2002
criteria and serology. Liver function, hematologic profile and severity of
bleeding outcome were carefully documented. The association between symptoms,
liver and hematologic impairments with the type of dengue infection (classical
vs. hemorrhagic) and bleeding outcome (major vs. non-major) was tested. Dengue
fever was confirmed in 183 cases (12.5/100,000 population) and 144 cases were
analysed. 59.7% were dengue hemorrhagic fever, 3.5% were dengue shock syndrome
and there were 3 in-hospital deaths. Major bleeding outcome (gastrointestinal
bleeding, intracranial bleeding or haemoptysis) was present in 14.6%. Elevated
AST, ALT and bilirubin were associated with increasing severity of bleeding
outcome (all P < 0.05). Platelet count and albumin level were inversely
associated with increasing severity of bleeding outcome (both P < 0.001). With
multivariable analysis, dengue hemorrhagic fever was more likely in the presence
of abdominal pain (OR 1.1, 95% CI 0.02- 1.6) and elevated AST (OR 1.0, 95% CI 1.0
1.1) but the presence of pleural effusion (OR 5.8, 95% CI: 1.1-29.9) and elevated
AST (OR 1.008, 95% CI: 1.005-1.01) predicted a severe bleeding outcome. As a
conclusion, the common presence of a severe hemorrhagic form of dengue fever may
explain the rising death toll in recent outbreaks and the worst impairment in
liver and hematologic profiles was seen in major bleeding outcome.
PMID- 25134896
TI - The emergence of Leptospira borgpetersenii serovar Arborea as the dominant
infecting serovar following the summer of natural disasters in Queensland,
Australia 2011.
AB - The following research reports the emergence of Leptospira borgpetersenii serovar
Arborea as the dominant infecting serovar following the summer of disasters and
the ensuing clean up in Queensland, Australia during 2011. For the 12 month
period (1 January to 31 December) L. borgpetersenii serovar Arborea accounted for
over 49% of infections. In response to a flooding event public health officials
need to issue community wide announcements warning the population about the
dangers of leptospirosis and other water borne diseases. Communication with
physicians working in the affected community should also be increased to update
physicians with information such as clinical presentation of leptospirosis and
other waterborne diseases. These recommendations will furnish public health
officials with considerations for disease management when dealing with future
disaster management programs.
PMID- 25134897
TI - Screening of antiviral activities in medicinal plants extracts against dengue
virus using dengue NS2B-NS3 protease assay.
AB - Dengue virus infects millions of people worldwide and there is no vaccine or anti
dengue therapeutic available. Screening large numbers of medicinal plants for
anti-dengue activities is an alternative strategy in order to find the potent
therapeutic compounds. Therefore, this study was designed to identify anti-dengue
activities in nineteen medicinal plant extracts that are used in traditional
medicine. Local medicinal plants Vernonia cinerea, Hemigraphis reptans, Hedyotis
auricularia, Laurentia longiflora, Tridax procumbers and Senna angustifolia were
used in this study. The highest inhibitory activates against dengue NS2B-NS3pro
was observed in ethanolic extract of S. angustifolia leaves, methanolic extract
of V. cinerea leaves and ethanol extract of T. procumbens stems. These findings
were further verified by in vitro viral inhibition assay. Methanolic extract of
V. cinerea leaves, ethanol extract of T. procumbens stems and at less extent
ethanolic extract of S. angustifolia leaves were able to maintain the normal
morphology of DENV2-infected Vero cells without causing much cytopathic effects
(CPE). The percentage of viral inhibition of V. cinerea and T. procumbens
extracts were significantly higher than S. angustifolia extract as measured by
plaque formation assay and RT-qPCR. In conclusion, The outcome of this study
showed that the methanolic extract of V. cinerea leaves and ethanol extract of T.
procumbens stems possessed high inhibitory activates against dengue virus that
worth more investigation.
PMID- 25134898
TI - Larvicidal efficacy screening of Anacardaciae crude extracts on the dengue
hemorrhagic vector, Aedes aegypti.
AB - Vector-borne diseases are still rife because of the re-emergence of diseases
transmitted by mosquitoes. The objective of this paper is to evaluate the
larvicidal efficacy of crude leaf extract of Mangifera indica, Gluta renghas, and
Melanochyla fasciculiflora against vector of dengue hemorrhagic fever, Aedes
aegypti. These plant species are endemic species and widely distributed in
Malaysian forests. Leaves of Ma. indica, G. renghas and M. fascculiflora were
collected from Teluk Bahang National Park, Penang Malaysia. Fractions of leaves
were segregated, air-dried, powdered and extracted using Soxhlet with methanol.
The solvent was removed by using rotary evaporator to obtain the crude extract.
Using WHO standard larval bioassay test method, third instar larvae of Aedes
aegypti were exposed to concentration ranging from 200- 4500 ppm of methanol
extract for all plant species. Larval mortality was observed after 24 hours
exposure. The highest susceptibility and toxicity was recorded by Mangifera
indica with the lowest concentration at 800 ppm followed by M. fasciculiflora and
G. renghas. This indicates that crude plant extract is very effective in killing
Ae. aegypti mosquitoes. This finding may lead to new low cost alternative,
environmentally friendly method for mosquito control programs. To our knowledge,
this is the first report on larvicidal bioefficacy from endemic Malaysian plants.
PMID- 25134899
TI - Prevalence and genotype of Giardia duodenalis from faecal samples of stray dogs
in Hualien city of eastern Taiwan.
AB - Giardia duodenalis is a zoonotic protozoan parasite that causes diarrhea through
waterborne transmission or fecal-oral infection. The cysts are chlorine-resistant
and, therefore, can pollute drinking water and induce a pandemic disease. In this
study, we aimed to detect G. duodenalis infection in stray dogs in Hualien,
Taiwan. We collected faecal samples from 118 dogs and amplified DNA sequences of
the beta-giardin gene by nested polymerase chain reactions (nested PCR). Eleven
of the 118 faecal samples tested positive for the parasite. The genotype analysis
of the 11 samples indicated that 7 samples belonged to assemblage C and four
samples belonged to assemblage D. Our study provided a better understanding of
the infection rate and genotypes of G. duodenalis in dogs from Hualien City, and
human infection could not be induced by this zoonotic infection pathway in
Hualien City.
PMID- 25134900
TI - Trypanosoma brucei brucei infected rats: micronucleated polychromatic
erythrocytes.
AB - The emergence of bone marrow micronucleated polychromatic erythrocytes (MN-PCE)
in rats experimentally infected with Trypanosoma brucei brucei was examined in
order to understand the bone marrow effects in trypanosomiasis infection. Bone
marrow was collected for micronucleus assay while blood samples were collected
from infected rat for hematological analysis. The results showed evidence of MN
PCE at 12.75 +/- 0.65 micronuclei/ 1000 PCE and 9.60 +/- 2.95 micronuclei/1000
PCE for rats infected for 21 days and 14 days respectively. The hematology
examination revealed changes in packed cell volume, haemoglobin and red blood
cells with concomitant increase in parasitemia. This study revealed that the
generation of MN-PCE was induced by an acute infection of T. b. brucei in rats
and this highlights an important phase in the pathogenesis of the disease that
may indicate possible damage to genetic information.
PMID- 25134901
TI - A pre-enrichment step is essential for detection of Campylobacter sp. in turbid
pond water.
AB - This work aimed to detect Campylobacter species from naturally contaminated
turbid pond water by PCR. A total of 16 water samples were collected from a
turbid village pond. Four methods of DNA extraction were applied to centrifuge
pellets from eight 100 ml pond water samples prior to attempted detection of
Campylobacter by PCR without an enrichment step. These methods were (1) Tris-HCl
and sodium dodecyl sulfate followed by phenol:chloroform:isoamylalcohol
extraction followed by treatment with DNA clean up kit, (2) proteinase K, (3)
Chelex(r) 100, and (4) boiling. The other eight pond water samples (10 ml and 100
ml) were filtered and filters were incubated overnight in Preston enrichment
broth. The centrifuge pellets obtained from enrichment cultures were treated by
proteinase K for DNA extraction. Primers CF03 and CF04 for the flagellin genes
(flaA and flaB) of Campylobacter jejuni and Campylobacter coli were used for
amplifying the extracted DNA. The DNA extracted from eight-100 ml pond water
samples that were not subject to selective enrichment was never amplified with
primers CF03 and CF04, hence Campylobacter was not detected. In contrast, the DNA
that was from samples that were subjected to a selective enrichment step in
Preston broth prior to PCR assay always gave amplified bands of 340-380 bp,
therefore the presence of Campylobacter was confirmed. Detection of
campylobacters from naturally contaminated, turbid, environmental water may not
be feasible by direct PCR assay because of low numbers and the presence of high
concentration of humic matter and other PCR inhibitors. The enrichment of water
samples in selective broth, however, facilitated PCR detection of Campylobacter
probably by increasing cell number and by diluting PCR inhibitors.
PMID- 25134902
TI - Identification of Angiostrongylus cantonensis and other nematodes using the SSU
rDNA in Achatina fulica populations of Metro Manila.
AB - Angiostrongylus cantonensis is a parasitic nematode that causes eosinophilic
meningitis in humans. Accidental infection occurs by consumption of contaminated
intermediates, such as the giant African land snail, Achatina fulica. This study
surveyed the presence of A. cantonensis juveniles in A. fulica populations from
12 sites in Metropolitan Manila, Philippines using the SSU rDNA. Fourteen
distinct sequences from 226 nematodes were obtained; of these, two matched A.
cantonensis and Ancylostoma caninum, respectively, with 100% identity. Exact
identities of the remaining twelve sequences could not be determined due to low
percent similarities. Of the sequenced nematodes, A. cantonensis occurred with
the highest frequency (139 out of 226). Most of these (131 out of 139) were
collected in just one area in Quezon City. Nematode infection of A. fulica in
this area and two others from Makati and another area in Quezon City,
respectively, were highest, combining for 95% of the total infection. Ancylostoma
caninum, on the other hand, was detected in four different sites. A. caninum is a
canine parasite, and this is the first report of the nematode in A. fulica. These
results cause public health concerns as both A. cantonensis and A. caninum are
zoonotic to humans.
PMID- 25134903
TI - The blow fly, Chrysomya megacephala, and the house fly, Musca domestica, as
mechanical vectors of pathogenic bacteria in Northeast Thailand.
AB - The Oriental latrine fly, Chrysomya megacephala (Fabricius) (Diptera:
Calliphoridae) and the house fly, Musca domestica L., (Diptera: Muscidae) are
synanthropic flies which are adapted to live in close association with human
habitations, thereby making them likely mechanical vectors of several pathogens
to humans. There were two main aims of this study. The first aim was to determine
the prevalence of these two fly species from five types of human habitations
including: fresh-food markets, garbage piles, restaurants, school cafeterias and
paddy fields, in the Muang Ubon Ratchathani and Warinchamrap districts of Ubon
Ratchathani province of Northeast Thailand. Flies collection were conducted
monthly from September 2010-October 2011 using a reconstructable funnel trap,
containing 1 day-tainted beef offal as bait. A total of 7 750 flies (6 401 C.
megacephala and 1 349 M.domestica) were collected. The second aim was to examine
the potential of these flies to carry pathogenic bacteria. Bacteria were isolated
from 994 individual flies collected using a sweep net (555 C. megacephala and 439
M. domestica). A total of 15 bacterial genera were isolated from the external
surfaces, comprising ten genera of gram-negative bacteria and five gram-positive
bacteria. The most common bacteria isolated from both species were coagulase
negative staphylococci, followed by Streptococcus group D non-enterococci. Human
pathogenic enteric bacteria isolated were Salmonella sp., Shigella sp.,
Escherichia coli O157:H7, Salmonella typhi, Bacillus sp., and Enterococcus sp.,
of which S. typhi is the first report of isolation from these fly species. Other
human pathogens included Staphylococcus aureus and Pseudomonas aeruginosa. Not
only were the number of C. megacephala positive for bacteria significantly higher
than for M. domestica, but they were also carrying ~11-12 times greater bacterial
load than M. domestica. These data suggest that both fly species should be
considered potential mechanical vectors of bacterial pathogens associated with
human habitations year-round in this region of Northeast Thailand.
PMID- 25134904
TI - Seroprevalence of Trypanosoma cruzi in stray and pet dogs in Grenada, West
Indies.
AB - American trypanosomiasis (Chagas disease) caused by the protozoan parasite
Trypanosoma cruzi is endemic to parts of South America and the Caribbean.
Infected dogs are important in the epidemiology of the parasite as they can play
a role in the transmission of the parasite to humans. A total of 399 dog sera
(242 stray and 157 pet dogs) were examined for T. cruzi infection; using a
qualitative immunochromatographic dipstick test, based on recombinant antigens
specific for American trypanosomiasis (Trypanosoma detect rapid test; InBios
international, Inc., Seattle, Washington). Overall seroprevalence for T. cruzi
was estimated at 10.5% (95% confidence interval: 7.5% to 13.5%); with stray dogs
being significantly more affected (p<0.05, chi2). Results from this study
indicate that dogs in Grenada are moderately exposed to T. cruzi compared to
other areas in the region.
PMID- 25134905
TI - Morphology of puparia of flesh flies in Thailand.
AB - Puparia of five flesh fly species were investigated for forensic study.
Boettcherisca nathani (Lopes, 1961), Boettcherisca peregrina (Robineau-Desvoidy,
1830), Lioproctia pattoni (Senior-White, 1924), Liopygia ruficornis (Fabricius,
1794) and Parasarcophaga (Liosarcophaga) dux (Thomson, 1869) were examined with a
scanning electron microscopy (SEM). Differences between species were found in the
number and arrangement of papillae in the anterior spiracle, the shape of
intersegmental spines between the prothorax and mesothorax and the pattern of
spiracular tufts at the posterior spiracle. The anterior spiracle of B. nathani
had two rows, comprising 21-27 papillae; while those of B. peregrina and L.
pattoni had one or two irregular rows with 24-26 and 20-28 papillae,
respectively. Anterior spiracle of L. ruficornis and P. dux had one row of 10-15
papillae. Intersegmental spines between the prothorax and mesothorax and pattern
of spiracular tufts at the posterior spiracle are morphologically different. L.
ruficornis and P. dux puparia are similar, but the position of the interslit
plate between the inner and middle spiracular slits was found to be an important
attribute to separate both species. Morphometric analysis on the length and width
of puparia of these species revealed statistically different among them. The key
for identifying puparia of forensically important flesh flies has been provided.
PMID- 25134906
TI - Seasonal occurrence and habitat of two pennellids (Copepoda, Siphonostomatoida)
infecting marine ranched black scraper and Korean rockfish in Korea.
AB - The seasonal occurrence and habitat of two parasitic copepods, Peniculus
minuticaudae (Shiino, 1956) and Peniculus truncatus (Shiino, 1956)
(Siphonostomatoida, Pennellidae) infecting the fins of black scraper Thamnaconus
modestus and Korean rockfish Sebastes schlegelii, respectively were investigated.
The fishes were collected from Tongyeong marine living resources research and
conservation center, southern coast of Korea as five per month for two years from
July 2011 to June 2013. In total, 391 copepods of P. minuticaudae were collected
in two years, in contrast to P. truncatus. Prevalence was 85%, mean intensity was
3.25, and maximum intensity was 33. Season wise, the infestation was observed as
the highest in autumn (September-November) season, and the lowest in winter
(December- February). It was infested only on fins of black scrapers. Abundance
of P. minuticaudae was found on the pectoral fin (43.5%), followed by anal
(22.5%), second dorsal (20.5%) and caudal fins (13.5%). Statistically significant
interactions were observed between season, infestation and infected regions
(P<0.001). It is also reported for the first time in Korea from the fins of wild
threadsail filefish Stephanolepis cirrhifer from Busan, Jeju, Tongyeong and Yeosu
fish markets. It can be a new record on its host and localities. A total of 51 P.
truncatus were collected with the prevalence of 37.5%, mean intensity of 0.37 and
maximum intensity of 6. Season wise, infestation was observed as the highest in
summer (June-August), and the lowest in winter. Attachment site was the dorsal
fin and not found from any other fins of rockfish. Statistically significant
interaction was observed between season and infestation (P<0.05). This is the
first report on the ecology of these two pennellids.
PMID- 25134908
TI - First record of chewing louse Heterodoxus spiniger (Insecta, Phthiraptera,
Boopidae) on stray dogs from northern region of Egypt.
AB - Heterodoxus spiniger is a rare chewing louse; infest dogs and occasionally cats
with expanding geographical distribution. This preliminary report is aimed to
record infestation of stray dogs in Kafr El-Sheikh city, Egypt by H. spiniger.
Two dogs out of 10 were naturally infected with H. spiniger. This report is the
first to demonstrate H. spiniger infestation on dogs in northern regions of Nile
delta of Egypt.
PMID- 25134907
TI - Genetic variability of the serine-rich Entamoeba histolytica protein gene in
clinical isolates from the United Arab Emirates.
AB - The genetic diversity of 20 Entamoeba histolytica isolates from asymptomatic
individuals from the UAE was investigated by analyzing polymorphism in the serine
rich E. histolytica gene (SREHP) by nested polymerase chain reaction (PCR)
amplification followed by restriction fragment length polymorphism (RFLP) on DNA
extracted directly from stool samples. The SREHP gene was successfully amplified
in 15 out of 20 E. histolytica-positive samples. Four out of the remaining five
isolates did not amplify for the SREHP gene. Despite successful amplification of
the SREHP gene in the fifth isolate, AluI digestion of the amplified PCR product
revealed no bands. As a result, all five samples were excluded from the study.
Twelve different profiles were obtained from the 15 successfully amplified
isolates. Thus, demonstrating extensive genetic variability and reinforcing the
argument that E. histolytica has an extremely polymorphic genetic structure.
Despite the sample size limitation, a finding in the study was the occurrence of
one profile common to one Indian isolate while another profile common to one
Pakistani isolate; indicating the possibility of clonal infection. Furthermore,
we found one isolate from a Bangladeshi expatriate identical to 2 asymptomatic
Bangladeshi isolates reported in an earlier study. No clear association between
the different genotypes and the study population demographics was noted. The
results also indicated the possibility of strains clustering by region.
PMID- 25134909
TI - A preliminary report on ants (Hymenoptera: Formicidae) recovered from forensic
entomological studies conducted in different ecological habitats in Malaysia.
AB - This study reported the ant species that were recovered from monkey carcasses in
three different ecological habitats in Malaysia. The study was conducted from 9
May - 10 October 2007, 6 May - 6 August 2008 and 26 May - 14 July 2009 in
forested area (Gombak, Selangor), coastal area (Tanjong Sepat, Selangor) and
highland area (Bukit Cincin, Pahang), respectively. Monkey carcass was used as a
model for human decomposition in this study. A total of 4 replicates were used in
each of the study sites. Ants were observed to prey on eggs, larvae, pupae and
newly emerged flies. This study found that ant species could be found at all
stages of decomposition, indicating that ants were not a significant indicator
for faunal succession. However, different species of ants were obtained from
monkey carcasses placed in different ecological habitats. Cardiocondyla sp. was
only found on carcasses placed in the coastal area; while Pheidole longipes,
Hypoponera sp. and Pachycondyla sp. were solely found on carcasses placed in the
highland area. On the other hand, Pheidologeton diversus and Paratrechina
longicornis were found in several ecological habitats. These data suggests that
specific ant species can act as geographic indicators for different ecological
habitats in forensic entomology cases in Malaysia.
PMID- 25134910
TI - Quantification of parasite density in 200 microscopic fields underestimates the
parasitemia level in malaria patients.
AB - The determination of parasitemia in the diagnosis of malaria is a routine
practice because it assists the selection of treatment. The techniques used for
estimating parasitemia are based on leukocyte counts or on a fixed volume of
blood examined in a microscopic field. This study evaluated the concordance
between parasitemia estimated by counting parasites in 200 microscopic fields and
by counting parasites per 500 leukocytes using the automated leukocyte count as a
reference. This study included 403 patients with acute malaria. The parasitemia
levels obtained by each method varied greatly. A large discrepancy was observed
between the 2 methods with respect to parasitemia results, with 17.6% and 82.4%
of the values being overestimates and underestimates, respectively, compared to
quantification by the automated leukocyte counts. Thus, these findings reveal the
inaccuracy of this method and should be considered by health professionals
involved in clinical management of the disease.
PMID- 25134911
TI - Different profile of intestinal protozoa and helminthic infections among patients
with diarrhoea according to age attending a rural hospital in southern Ethiopia.
AB - The aim of this study was to analyze the association of intestinal parasitic
diseases with age and gender in patients with diarrhea attending a rural hospital
in southern Ethiopia in the period 2007-2012. A total of 32,191 stool examination
was performed in patients who presented with diarrhea. The overall prevalence of
intestinal parasites in the present study was 26.5%. Predominant parasites
detected were Giardia lamblia (15.0%), Entamoeba histolytica/dispar (5.4%), and
Ascaris lumbricoides (5.0%). The median of age of diarrheal patients with
Hymenolepis species, Schistosoma mansoni and G. lamblia was significantly lower
(5 y., 10.5 y., and 18 y., respectively; p<0.001). The median age of diarrheal
patients with Taenia species, S. stercoralis, and E. histolytica/dispar was
significantly higher (24 y., 24 y., and 20 y., respectively; p<0.01). In
conclusion, Giardia lamblia was the most prevalent intestinal parasite and the
profile of intestinal parasitic infections is influenced by age.
PMID- 25134912
TI - The impact of HIV-1 on neurogenesis: implications for HAND.
AB - HIV-1 infection, in addition to its destructive effects on the immune system,
plays a role in the development of neurocognitive deficits. Indeed up to 50% of
long-term HIV infected patients suffer from HIV-associated neurocognitive
disorders (HAND). These deficits have been well characterized and defined
clinically according to a number of cognitive parameters. HAND is often
accompanied by atrophy of the brain including inhibition of neurogenesis,
especially in the hippocampus. Many mechanisms have been proposed as contributing
factors to HAND including induction of oxidative stress in the central nervous
system (CNS), chronic microglial-mediated neuroinflammation, amyloid-beta (Abeta)
deposition, hyperphosphorylated tau protein, and toxic effects of combination
antiretroviral therapy (cART). In these review we focus solely on recent
experimental evidence suggesting that disturbance by HIV-1 results in impairment
of neurogenesis as one contributing factor to HAND. Impaired neurogenesis has
been linked to cognitive deficits and other neurodegenerative disorders. This
article will highlight recently identified pathological mechanisms which
potentially contribute to the development of impaired neurogenesis by HIV-1 or
HIV-1-associated proteins from both animal and human studies.
PMID- 25134914
TI - Interstitial lung disease during targeted therapy in metastatic renal cell
carcinoma: a case series from three centres.
AB - Interstitial lung disease (ILD) is an adverse event which occurs also during
targeted treatment of patients with metastatic renal cell carcinoma (mRCC).
Experiences on ILD-management in mRCC remain limited. mRCC patients treated with
everolimus, temsirolimus, or sunitinib at three centres from January 2006 until
December 2009 were analysed, retrospectively. Medical records and imaging
studies, as well as clinical course, the incidence, diagnostic measures,
treatment, and outcome of ILD were assessed. Twenty-six ILD patients (11 %) were
identified out of 237 mRCC patients. Median treatment until ILD-diagnosis was 3.8
(range: 1-21.5) months. The ILD-frequency was 2.7 % (n = 6/226) during sunitinib
therapy and 19.8 % (n = 20/101) during m-TOR-inhibitor treatment. Cough was the
prevailing symptom (69.2 %, n = 18). Bronchoalveolar lavage reviled often
lymphocytic (42.9 %, n = 6/14) or eosinophilic cellularity (28.6 %, n = 4/14).
Dose reduction (42.3 %, n = 11), treatment interruption (46.2 %, n = 12) or
termination (23.1 %, n = 6), and steroid application (34.6 %, n = 9) were common
measures in ILD. Interestingly, eosinophilic ILD required pulsed steroids.
Improvement occurred in 73.7 % of symptomatic patients. Continuation of targeted
therapies was warranted in 65.4 % of ILD patients. No patient died from ILD. ILD
during targeted mRCC treatment is common, and supportive measures should be
adapted to the clinical course, and potentially in dependence of BAL findings. Re
exposure to targeted therapies appears feasible.
PMID- 25134916
TI - Metastatic parenchymal renal squamous cell carcinoma with hypercalcemia.
PMID- 25134915
TI - Single-strand conformational polymorphism analysis of a common single nucleotide
variation in WRAP53 gene, rs2287499, and evaluating its association in relation
to breast cancer risk and prognosis among Iranian-Azeri population.
AB - The WRAP53 (WD40-encoding RNA antisense to p53) gene encodes an antisense RNA,
essential for p53 stabilization and induction upon DNA damage. Single nucleotide
polymorphisms (SNPs) in WRAP53 have been associated with risk of cancer, which
strengthens the role of WRAP53 in the pathogenesis of human malignancies. In
fact, WRAP53 has been considered as a candidate cancer susceptibility gene.
Accordingly, we performed a study to examine the association of a frequent
genetic variation in WRAP53, rs2287499 (C/G), with breast cancer risk and
prognosis among Iranian-Azeri population. A case-control association study,
including 206 cases and 203 controls from Iranian-Azeri population, was
conducted. Genomic DNA was extracted from peripheral blood and tumor samples by
salting-out method. SNP genotyping was carried out by polymerase chain reaction
based single-strand conformational polymorphism (PCR-SSCP) technique. The
sequence variation of SSCP banding patterns was determined by sequencing. The
collected data were analyzed through statistical package for the social sciences
software, using Chi-square (chi (2)) or Fisher's exact tests, with a significance
level of 0.05. No significant differences in the allele and genotype frequencies
between cases and controls were detected. Similarly, no significant associations
between genotypes and clinicopathological data were observed. Concisely, no
significant overall associations between rs2287499 and breast cancer risk and
prognosis were detected in the studied population. The rs2287499 SNP is not
associated with breast cancer predisposition in Iranian-Azeri women; it also
cannot be used as a molecular biomarker to predict breast cancer prognosis in
Iranian-Azeri population.
PMID- 25134913
TI - Novel function of PITH domain-containing 1 as an activator of internal ribosomal
entry site to enhance RUNX1 expression and promote megakaryocyte differentiation.
AB - INTRODUCTION: Altered gene expression coincides with leukemia development and may
affect distinct features of leukemic cells. PITHD1 was significantly
downregulated in leukemia and upregulated upon PMA induction in K562 cells
undergoing megakaryocyte differentiation. We aimed to study the function of
PITHD1 in megakaryocyte differentiation. MATERIALS AND METHODS: K562 cells and
fetal liver cells were used for either overexpression or downregulation of PITHD1
by retroviral or lentiviral transduction. FACS was used to detect the expression
of CD41 and CD42 to measure megakaryocyte differentiation in these cells. Western
blot and quantitative RT-PCR were used to measure gene expression. Dual
luciferase assay was used to detect promoter or internal ribosomal entry site
(IRES) activity. RESULTS: Ectopic expression of PITHD1 promoted megakaryocyte
differentiation and increased RUNX1 expression while PITHD1 knockdown showed an
opposite phenotype. Furthermore, PITHD1 efficiently induced endogenous RUNX1
expression and restored megakaryocyte differentiation suppressed by a dominant
negative form of RUNX1. PITHD1 regulated RUNX1 expression at least through two
distinct mechanisms: increasing transcription activity of proximal promoter and
enhancing translation activity of an IRES element in exon 3. Finally, we
confirmed the function of PITHD1 in regulating RUNX1 expression and
megakaryopoiesis in mouse fetal liver cells. CONCLUSION AND SIGNIFICANCE: PITHD1
was a novel activator of IRES and enhanced RUNX1 expression that subsequently
promoted megakaryocyte differentiation. Our findings shed light on understanding
the mechanisms underlying megakaryopoiesis or leukemogenesis.
PMID- 25134917
TI - Multimodality treatment of osteosarcoma of the jaw: a single institution
experience.
AB - Osteosarcomas of the jaws are rare mesenchymal tumors frequently diagnosed in the
fourth decade of life which account for 6 % of all osteosarcomas. This study
evaluated the efficacy on the patients outcome of multimodality treatment
consisting of surgery, chemotherapy and radiotherapy. The records of 22 patients
affected by jaw osteosarcoma treated with a combination of surgery, poly
chemotherapy and adjuvant radiotherapy in selected cases were reviewed. Response
rate, progression-free survival and overall survival were evaluated. Neoadjuvant
chemotherapy resulted in an overall response rate of 83.3 %, necrosis of grade I
or II was obtained, respectively, in 44.4 and 55.6 % of the patients, and surgery
was radical in all patients. At a median follow-up of 60 months, the 5-year
progression-free survival and overall survival were 73.5 and 77.4 %,
respectively. These outcome parameters significantly correlated with age at
diagnosis and grade of chemotherapy-induced necrosis. A complex multimodality
approach including chemotherapy and radiotherapy, along with radical surgery, can
maximize the outcome of patients affected by osteosarcoma of the jaws.
PMID- 25134918
TI - Clinical value of circulating tumor cells for the prognosis of postoperative
transarterial chemoembolization therapy.
AB - The aim of this study was to clarify circulating tumor cells (CTCs) count could
reflect the effect of postoperative transarterial chemoembolization therapy. A
single-blind, two-parallel group, randomized trial was conducted in Guangdong
General Hospital, Guangzhou, China, with patients: (1) with biopsy-confirmed
hepatocellular carcinoma (HCC) and (2) undergoing partial resection. Patients in
transarterial chemoembolization (TACE) group received TACE 1 month after
resection, while control group received no managements. The time points for blood
collection to count CTCs were as follows: (1) 1 month after resection (also 1 day
before TACE); (2) 1 month after TACE; (3) 2 months after TACE; (4) 3 months after
TACE; (5) 6 months after TACE; and (6) 1 year after TACE. A diagnosis of
recurrence was based on computed tomography scans, magnetic resonance imaging, or
digital subtraction angiography. We compared recurrence rate (RR) and CTC counts
between groups. Between July 2010 and July 2012, 171 patients (TACE group: n =
81; control group: n = 90) were recruited. After TACE, mean CTC count in TACE
group was 1.32 (CI 2.59-3.34), compared with 3.65 (CI 3.43-3.88) in control group
(F = 200.89, P<0.05). CTCs counts were statistically significantly between groups
at post-TACE time points. In addition, RR of TACE group was 25.9 % (21/81), while
the number was 56.7 % (51/90) in control group. RR was statistically
significantly between groups (P = 0.031). CTCs count was an important prognostic
parameter for postoperative TACE on HCC recurrence.
PMID- 25134919
TI - CISD2 expression is a novel marker correlating with pelvic lymph node metastasis
and prognosis in patients with early-stage cervical cancer.
AB - The CDGSH iron sulfur domain2 (CISD2) is an evolutionarily conserved gene. It
functions to control mammalian life span and regulate human breast cancer cells
proliferation. However, the characteristics of CISD2 expression and its
clinical/prognostic significance are unclear in human tumor. Our study aimed to
investigate the expression pattern and clinicopathological significance of CISD2
in patients with early-stage cervical cancer. The mRNA and protein expression
levels of CISD2 were analyzed in eight cervical cancer cell lines and eight
paired cervical cancer tumors by real-time PCR and Western blotting,
respectively. Immunohistochemistry was performed to examine CISD2 protein
expression in paraffin-embedded tissues from 149 early-stage cervical cancer
patients. Statistical analyses were used to evaluate the clinicopathological
significance of CISD2 expression. CISD2 expression was significantly upregulated
in cervical cancer cells at both the mRNA and protein levels. Statistical
analysis showed a significant correlation of CISD2 expression with the squamous
cell carcinoma antigen (P = 0.000), myometrium invasion (P = 0.003), recurrence
(P = 0.012), lymphovascular space involvement (P = 0.019) and especially pelvic
lymph node metastasis (PLNM; P = 0.000). Patients with higher CISD2 expression
had shorter overall survival duration than patients with lower CISD2 expression.
Multivariate analysis suggested that CISD2 expression might be an independent
prognostic indicator for the survival of patients with early-stage cervical
cancer. Our results for the first time suggested that high CISD2 expression was
closely correlated with PLNM and poor prognosis in early-stage cervical cancer
patients. CISD2 protein might be a novel biomarker for early-stage cervical
cancer progression.
PMID- 25134922
TI - Fetal cardiac interventricular septum: volume assessment by 3D/4D ultrasound
using spatio-temporal image correlation (STIC) and virtual organ computer-aided
analysis (VOCAL).
AB - OBJECTIVE: To determine reference values for fetal interventricular septum (IVS)
volume by 3D/4D ultrasound using spatio-temporal image correlation (STIC) and
virtual organ computer-aided analysis (VOCAL). METHODS: A prospective cross
sectional study was conducted on 200 consecutive normal low-risk pregnant women
at a gestational age ranging from 18w0d to 33w6d. The volume data sets of the
fetal heart were acquired by applying STIC to a four-chamber plane. IVS volume
was calculated offline using VOCAL with rotation of 30 degrees (six planes). To
assess the correlation of fetal IVS volume as a function of gestational age (GA),
Pearson's correlation coefficient (r) and polynomial regression models with
adjustments through the coefficient of determination (R(2)) were calculated. The
intra-class coefficient (ICC) was used to evaluate intra- and inter-observer
reproducibility. RESULTS: A good correlation between GA and fetal IVS volume (r =
0.827) was observed. The mean fetal IVS volume ranged from 0.13 +/- 0.03 cm(3)
(0.08-0.18 cm(3)) at 18wd0 of gestation to 1.33 +/- 0.37 cm(3) (0.41-1.98 cm(3))
at 33w6d. The best correlation between fetal IVS volume and GA was exponential:
fetal IVS volume = 0.11e(0.139*GA) (R(2 )= 0.785). A good intra- and inter
observer reliability were observed, with ICC = 0.999 and 0.991, respectively.
CONCLUSIONS: Reference values for fetal IVS volume using STIC and VOCAL by 3D/4D
ultrasound between 18w0d and 33w6d of gestation were determined and showed to be
reliable and concordant.
PMID- 25134920
TI - Breakeven prices for recording of indicator traits to reduce the environmental
impact of milk production.
AB - A breeding scheme using genomic selection and an indicator trait for
environmental impact (EI) was studied to find the most effective recording
strategy in terms of annual monetary genetic gain and breakeven price for the
recording of indicator traits. The breakeven price shows the investment space for
developing a recording system for an indicator trait. The breeding goal consisted
of three traits - milk production, functional trait and environmental impact -
with economic values of ?83, ?82 and ?-83, respectively. The first scenario
included only breeding goal traits and no indicator traits (NoIT). The other
scenarios included all three breeding goal traits and one indicator trait (IT)
for EI. The indicator traits were recorded on a large scale (stayability after
first lactation and stature), medium scale (live weight and greenhouse gases
(GHG) measured in the breath of the cow during milking) or small scale (residual
feed intake and total enteric methane measured in a respiration chamber). In the
scenario with stayability, the genetic gain in EI was over 11% higher than it was
in NoIT. The breakeven price of recording stayability was ?8 per record.
Stayability is easy to record in the national milk recording system, and its use
as an indicator trait for EI would not generate any additional recording costs.
Therefore, stayability would be a good indicator trait to use to mitigate EI. The
highest genetic gain in EI (23% higher compared to NoIT) was achieved when the
GHG measured in the breath of the cow was used as indicator trait. The breakeven
price for this indicator trait was ?29 per record in the reference population.
Ideally the recording of a specific indicator trait for EI would take place when:
(i) the genetic correlation between the IT and EI is high; and (ii) the number of
phenotypic records for the indicator trait is high enough to achieve a moderately
high reliability of direct genomic values.
PMID- 25134923
TI - Effectiveness of aldosterone antagonists for preventing atrial fibrillation after
cardiac surgery in patients with systolic heart failure: a retrospective study.
AB - Postoperative atrial fibrillation (POAF) is the most common arrhythmia after
cardiac surgery. There exist consistent experimental and clinical data suggesting
that aldosterone antagonists (AAs) may exert beneficial effects regarding
electrical and structural remodeling in failing myocardium. Recently, eplerenone
(EPL) has been found to reduce the incidence of nonsurgical AF when added to
guideline-recommended therapy in patients with systolic heart failure. Based on
these findings, we primarily aimed to evaluate by retrospective analysis the
impact of the two AAs, EPL and spironolactone (SPL), given at standard
therapeutic doses in preventing new-onset POAF in patients the majority of which
had a preoperative ejection fraction (EF) below 40%. A total of 332 patients (298
men/34 women, mean age 64.3 +/- 9 years) without history of AF were included in
this analysis; 132 of these patients received long-term EPL or SPL in addition to
beta-blockade/statins therapy and 200 patients received neither EPL nor SPL. All
patients underwent on-pump coronary artery bypass graft (80%) and/or valvular
surgery (20%). In the nonAA group (EF = 35.8 +/- 6%) 90/200 patients (45%) had
POAF, while in the AA group (EF = 36.2 +/- 5%) only 40/132 patients (30.3%)
developed POAF (P < 0.01, chi (2) test). Multivariate logistic regression
analysis revealed that only AAs and left atrial diameter significantly affected
the development of POAF even when adjusted for other clinical variables (P <
0.05). In conclusion, AAs significantly reduced the incidence of POAF when added
to standard heart failure therapy in patients undergoing on-pump cardiac surgery.
PMID- 25134925
TI - Metals in the caudal scutes of Morelet's crocodile (Crocodylus moreletii) from
the southern Gulf of Mexico.
AB - Caudal scutes were collected from 92 Morelet's crocodiles (Crocodylus moreletii)
between May and August 2012, in three Wildlife Management and Use Units (UMAs,
from its name in Spanish) and three wild sites in Campeche, Mexico. The UMAs are
intensive, with an ex situ approach to manage crocodiles in captivity. The
concentrations of arsenic, mercury, lead, nickel, cadmium and chromium were
analyzed in each sample. As and Pb were detected in all samples, Hg in 86 and Ni
in 74. The metal concentrations estimated were higher than most of the
concentrations reported for skin, tail tip and caudal scutes in other
crocodilians around the world. The concentration of As, Pb and Ni was
significantly greater in the free-ranging groups than in the captive groups in
UMAs (p < 0.05). Negative linear relationship was estimated between the snout
vent length and the concentration of Pb (in five groups) and Ni (in three
groups). In this region C. moreletii is exposed to metals contamination and more
studies are necessary to establish if represents a risk to their populations.
PMID- 25134926
TI - Aug-MIA-QSPR modeling of the soil sorption of carboxylic acid herbicides.
AB - Soil sorption, described as logK OC (the logarithm of the soil/water partition
coefficient normalized to organic carbon), was modeled using the augmented
multivariate image analysis applied to quantitative structure-property
relationship method for a series of 11 carboxylic acid herbicides. The
statistical model was found to be highly predictive and reliable to estimate logK
OC of other persistent organic pollutants in the soil, which are analogues of the
carboxylic acids used in the QSPR model. The QSPR model derived from images
corresponding to the chemical structures of the 11 herbicides is superior to the
uniparameter model based on the octanol/water partition coefficient (logP) and,
in addition, a pattern recognition model was built using principal component
analysis. This model allowed clustering and separating compounds with
low/moderate soil sorption from those with moderate/high soil sorption (compounds
with the aryloxy function) using the second principal component.
PMID- 25134927
TI - Preparation and pharmaceutical evaluation of new tacrolimus-loaded solid self
emulsifying drug delivery system.
AB - The purpose of this study was to develop a novel tacrolimus-loaded solid self
emulsifying drug delivery system (SEDDS) using Labrafac as an oil phase. The
ternary phase diagram was plotted with Labrafac, Labrasol and Lauroglycol used as
an oil, surfactant and co-surfactant, respectively. The liquid SEDDS formulated
with Labrasol, Lauroglycol and Labrafac (70:15:15, volume ratio) furnished the
smallest emulsion globule size. The solid SEDDS was obtained by spray-drying the
liquid mixture containing the liquid SEDDS with 5 % tacrolimus and silicon
dioxide. Furthermore, dissolution of tacrolimus from the solid SEDDS and
pharmacokinetics in rats was studied compared to the commercial product. The
solid SEDDS produced relatively larger emulsion globule size than that exhibited
by the corresponding liquid SEDDS. However, this size variation was not
significantly different. The solid SEDDS with approximately 280 nm emulsion
droplet size improved the dissolution of the drug compared to drug power and the
commercial product. It resulted in significantly higher plasma concentration, AUC
and Cmax, and shorter Tmax values than did the commercial product (p < 0.05). The
enormously enhanced oral bioavailability of tacrolimus in rats was attributed to
relatively faster absorption due to accelerated dissolution of the drug from the
solid SEDDS. Therefore, this novel solid SEDDS prepared with Labrafac as an oil
phase is an excellent way to achieve better bioavailability of tacrolimus given
via the oral route.
PMID- 25134924
TI - Managing chemotherapy-related cardiotoxicity in survivors of childhood cancers.
AB - In the US, children diagnosed with cancer are living longer, but not without
consequences from the same drugs that cured their cancer. In these patients,
cardiovascular disease is the leading cause of non-cancer-related morbidity and
mortality. Although this review focuses on anthracycline-related cardiomyopathy
in childhood cancer survivors, the global lifetime risk of other cardiovascular
diseases such as atherosclerosis, arrhythmias and intracardiac conduction
abnormalities, hypertension, and stroke also are increased. Besides
anthracyclines, newer molecularly targeted agents, such as vascular endothelial
growth factor receptor and tyrosine kinase inhibitors, also have been associated
with acute hypertension, cardiomyopathy, and increased risk of ischemic cardiac
events and arrhythmias, and are summarized here. This review also covers other
risk factors for chemotherapy-related cardiotoxicity (including both modifiable
and non-modifiable factors), monitoring strategies (including both blood and
imaging-based biomarkers) during and following cancer treatment, and discusses
the management of cardiotoxicity (including prevention strategies such as
cardioprotection by use of dexrazoxane).
PMID- 25134930
TI - Letter from the editor.
PMID- 25134929
TI - An approach to multiscale modelling with graph grammars.
AB - BACKGROUND AND AIMS: Functional-structural plant models (FSPMs) simulate
biological processes at different spatial scales. Methods exist for multiscale
data representation and modification, but the advantages of using multiple scales
in the dynamic aspects of FSPMs remain unclear. Results from multiscale models in
various other areas of science that share fundamental modelling issues with FSPMs
suggest that potential advantages do exist, and this study therefore aims to
introduce an approach to multiscale modelling in FSPMs. METHODS: A three-part
graph data structure and grammar is revisited, and presented with a conceptual
framework for multiscale modelling. The framework is used for identifying roles,
categorizing and describing scale-to-scale interactions, thus allowing
alternative approaches to model development as opposed to correlation-based
modelling at a single scale. Reverse information flow (from macro- to micro
scale) is catered for in the framework. The methods are implemented within the
programming language XL. KEY RESULTS: Three example models are implemented using
the proposed multiscale graph model and framework. The first illustrates the
fundamental usage of the graph data structure and grammar, the second uses
probabilistic modelling for organs at the fine scale in order to derive crown
growth, and the third combines multiscale plant topology with ozone trends and
metabolic network simulations in order to model juvenile beech stands under
exposure to a toxic trace gas. CONCLUSIONS: The graph data structure supports
data representation and grammar operations at multiple scales. The results
demonstrate that multiscale modelling is a viable method in FSPM and an
alternative to correlation-based modelling. Advantages and disadvantages of
multiscale modelling are illustrated by comparisons with single-scale
implementations, leading to motivations for further research in sensitivity
analysis and run-time efficiency for these models.
PMID- 25134928
TI - A bifunctional curcumin analogue for two-photon imaging and inhibiting
crosslinking of amyloid beta in Alzheimer's disease.
AB - In this report, we designed a highly bright bifunctional curcumin analogue CRANAD
28. In vivo two-photon imaging suggested that CRANAD-28 could penetrate the blood
brain barrier (BBB) and label plaques and cerebral amyloid angiopathies (CAAs).
We also demonstrated that this imaging probe could inhibit the crosslinking of
amyloid beta induced either by copper or by natural conditions.
PMID- 25134931
TI - A population-based study of pregnancy and delivery characteristics among women
with vulvodynia.
AB - INTRODUCTION: To examine pregnancy and delivery characteristics of women with and
without vulvodynia. METHODS: The authors analyzed 227 vulvodynia cases that were
less than 45 years old at pain onset; controls were age matched 1:1 to cases and
had no history of vulvar pain. Pregnancy and delivery events were assessed after
age at first vulvar pain onset (the reference age) in cases and a matched age in
controls. RESULTS: The authors observed no significant difference between cases
and controls in achieving pregnancy after reference age. Also, no difference in
pregnancy outcome was observed between cases and controls (P = 0.87). There was
an indication that cases were more likely to receive a Cesarean section delivery
(P = 0.07). In addition, 37.1% of cases who had vaginal delivery versus 11.3% of
controls (P < 0.01) reported pain at 2 months postpartum. Comparing only women
with vulvodynia, women who had intermittent pain versus constant pain were more
than twice as likely to have a pregnancy (adjusted odds ratio 2.26, 95% CI 1.10
4.60). CONCLUSIONS: Women with vulvodynia may be as likely as other women to
carry their pregnancy to birth; however, they may experience higher rates of
Cesarean section delivery and could reflect a selection towards those women with
vulvodynia who have inconsistent pain.
PMID- 25134933
TI - Alleviating symptoms of withdrawal from an opioid.
AB - INTRODUCTION: Patients who are discharged following surgery on an oral opioid,
and who have taken the drug for 2 or more weeks often experience withdrawal
symptoms when they try to discontinue the drug. CASE REPORT: Three weeks after
discharge, a 44-year-old female patient decided to reduce her oxycodone
(OxyContin((r))) dosage from 20 mg three times a day to 20 mg two times a day.
She experienced severe withdrawal symptoms. METHOD: To assist her in withdrawing
from the remainder of the drug, a protocol using ondansetron was developed.
RESULTS: After 10 days, the patient was opioid and withdrawal-symptom free.
CONCLUSION: Use of ondansetron along with tapering of the opioid was safe and
effective in preventing further withdrawal symptoms. This case should stimulate
research with a larger, more diverse population including those with both short
term and chronic opioid dependence.
PMID- 25134932
TI - Discovery of Fused Triazolo-thiadiazoles as Inhibitors of TNF-alpha:
Pharmacophore Hybridization for Treatment of Neuropathic Pain.
AB - INTRODUCTION: Neuropathic pain is a complex, chronic pain state that is usually
accompanied by tissue injury. With neuropathic pain, the nerve fibers themselves
may be damaged, dysfunctional, or injured. METHODS: A series of pharmacophoric
hybrids of substituted aryl semicarbazides incorporated into a fused triazolo
thiadiazole nucleus were synthesized and evaluated for neuropathic pain activity.
After the assessment of neurotoxicity and peripheral analgesic activity, the
compounds were evaluated in two peripheral neuropathic pain models, the chronic
constriction injury and partial sciatic nerve ligation, to assess their
antiallodynic and antihyperalgesic potential. RESULTS: Selected compounds
exhibiting promising efficacies (4b, 6a, and 7e) revealed median effective dose
(ED50) values ranging from 7.62-28.71 mg/kg in four behavioral assays of
allodynia and hyperalgesia (spontaneous pain, tactile allodynia, cold allodynia,
and mechanical hyperalgesia). Studies carried out to assess the underlying
mechanism revealed that compounds suppressed the inflammatory component of the
neuropathic pain by inhibiting tumor necrosis factor (TNF)-alpha and preventing
oxidative and nitrosative stress. CONCLUSION: Using a hybrid design approach, the
present study identified novel chemical compounds that could be a potential lead
for the treatment of neuropathic pain.
PMID- 25134934
TI - Outcomes in pain medicine: a brief review.
AB - Pain, and particularly chronic pain, is a difficult outcome to measure due to its
subjective and multidimensional nature. The Institute of Medicine estimates that
100 million Americans have chronic pain with a cost exceeding half a trillion
dollars per year. There is a pressing need to identify appropriate outcome
measures to better select and evaluate treatment modalities for these patients.
It is also important that we demonstrate an evidence basis for these decisions
given the current practice standard. Appropriate selection and implementation of
these outcome measures can help accomplish both goals. The purpose of this review
is to explore the difficulties and opportunities unique to pain outcome measures.
The scope of the problem and impetus for implementation of appropriate measures
is initially discussed, followed by requisite evaluation criteria for any
measurement instrument. The authors then review frequently employed tools for
measuring pain outcomes ranging from univariable and single domain scales to
multidimensional instruments. A discussion of possible behavioral and objective
measures is pursued, as well as measures of statistical and treatment efficacy.
The article closes with a review of recent and ongoing efforts to validate and
standardize pain outcome measures and suggests directions for future clinical and
research assessment.
PMID- 25134937
TI - Redox-reversible niobium-doped strontium titanate decorated with in situ grown
nickel nanocatalyst for high-temperature direct steam electrolysis.
AB - Composite cathodes based on Sr0.94Ti0.9Nb0.1O3 (STNO) can be utilized for direct
steam electrolysis; however, the insufficient electrocatalytic activity limits
electrode performance and current efficiency. In this work, redox-reversible
(Sr0.94)0.9(Ti0.9Nb0.1)0.9Ni0.1O3 (STNNO) with A-site deficiency and B-site
excess has been designed as a cathode material in an oxide-ion-conducting solid
oxide electrolyzer for direct steam electrolysis. The XRD, TEM, SEM, EDS, TGA and
XPS results together confirm that the exsolution or dissolution of Ni
nanoparticles anchored on the STNO surface is completely reversible in the redox
cycles. The electrical properties of STNO and STNNO are investigated and
correlated to electrode performances. The current efficiency with an STNNO
cathode is enhanced by about 20% compared to the values with a bare STNO cathode
in 5% H2O/H2/Ar or 5% H2O/Ar at 800 degrees C. The synergetic effect of
catalytically active nickel nanoparticles and the redox-stable STNO skeleton
contributes to the improved performance and excellent stability of the cathode
for steam electrolysis.
PMID- 25134935
TI - Mesenchymal stem cells overexpressing integrin-linked kinase attenuate left
ventricular remodeling and improve cardiac function after myocardial infarction.
AB - In the present study, we investigated whether mesenchymal stem cells (MSCs)
overexpressing integrin-linked kinase (ILK) might regulate ventricular remodeling
and cardiac function in a porcine myocardial infarction model. ILK-modified MSCs
(ILK-MSCs) (n = 8), MSCs (n = 8) or placebo (n = 8) were injected into peri
infarct myocardium 7 days after ligation of the left anterior descending coronary
artery. ILK expression was confirmed by immunofluorescence, real-time PCR,
Western blot analysis, and flow cytometry. In vitro assays indicated increased
proliferation and reduced apoptosis of MSCs due to overexpression of ILK.
Echocardiographic, single-photon emission computed tomography and positron
emission tomography analyses demonstrated preserved cardiac function and
myocardial perfusion. Reduced fibrosis, increased cardiomyocyte proliferation,
and enhanced angiogenesis were observed in the ILK-MSC group. Reduced apoptosis,
as demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end
labeling analysis, was also noted. In conclusion, ILK promotes MSC proliferation
and suppresses apoptosis. ILK-MSC transplantation improves ventricular remodeling
and cardiac function in pigs after MI. It is associated with increased
angiogenesis, reduced apoptosis, and increased cardiomyocyte proliferation. This
may represent a new approach to the treatment of post-infarct remodeling and
subsequent heart failure.
PMID- 25134936
TI - Hierarchical functional data with mixed continuous and binary measurements.
AB - Motivated by objective measurements of physical activity, we take a functional
data approach to longitudinal data with simultaneous measurement of a continuous
and a binary outcomes. The regression structures are specified as smooth curves
measured at various time-points with random effects that have a hierarchical
correlation structure. The random effect curves for each variable are summarized
using a few important principal components, and the association of the two
longitudinal variables is modeled through the association of the principal
component scores. We use penalized splines to model the mean curves and the
principal component curves, and cast the proposed model into a mixed effects
model framework for model fitting, prediction and inference. Via a
quasilikelihood type approximation for the binary component, we develop an
algorithm to fit the model. Data-based transformation of the continuous variable
and selection of the number of principal components are incorporated into the
algorithm. The method is applied to the motivating physical activity data and is
evaluated empirically by a simulation study. Extensions for different types of
outcomes are also discussed.
PMID- 25134938
TI - Cytogenetic mapping of the Muller F element genes in Drosophila willistoni group.
AB - Comparative genomics in Drosophila began in 1940, when Muller stated that the
ancestral haploid karyotype of this genus is constituted by five acrocentric
chromosomes and one dot chromosome, named A to F elements. In some species of the
willistoni group such as Drosophila willistoni and D. insularis, the F element,
instead of a dot chromosome, has been incorporated into the E element, forming
chromosome III (E + F fusion). The aim of this study was to investigate the scope
of the E + F fusion in the willistoni group, evaluating six other species.
Fluorescent in situ hybridization was used to locate two genes of the F element
previously studied-cubitus interruptus (ci) and eyeless (ey)-in species of the
willistoni and bocainensis subgroups. Moreover, polytene chromosome photomaps
corresponding to the F element (basal portion of chromosome III) were constructed
for each species studied. In D. willistoni, D. paulistorum and D. equinoxialis,
the ci gene was located in subSectction 78B and the ey gene in 78C. In D.
tropicalis, ci was located in subSection 76B and ey in 76C. In species of the
bocainensis subgroup, ci and ey were localized, respectively, at subsections 76B
and 76C in D. nebulosa and D. capricorni, and 76A and 76C in D. fumipennis.
Despite the differences in the subsection numbers, all species showed the same
position for ci and ey. The results confirm the synteny of E + F fusion in
willistoni and bocainensis subgroups, and allow estimating the occurrence of this
event at 15 Mya, at least.
PMID- 25134940
TI - Novel agents in CNS myeloma treatment.
AB - Central nervous system localization of multiple myeloma (CNS-MM) accounts for
about 1% of all MM.Treatment is still unsatisfactory. Many treatments have been
described in the literature: chemotherapy (CHT), intrathecal therapy (IT), and
radiotherapy (RT), with survivals reported between one month and six months.
Recent drugs such as the immunomodulatory drugs (IMiDs) and proteasome inhibitors
(bortezomib) have changed the treatment of patients with MM, both younger and
older, with a significant improvement in response and survival. The activity of
new drugs in CNSMM has been reported but is still not well known. Bortezomib does
not cross the blood brain barrier (BBB), and IMID's seem to have only a minimal
crossover. The role of novel agents in CNS MM management will be discussed as
well as the potential role of other new immunomodulatory drugs (pomalidomide) and
proteasome inhibitors that seem to cross the BBB and hold promise into the
treatment of this rare and still incurable localization of the disease.
PMID- 25134939
TI - Bone complications among prostate cancer survivors: long-term follow-up from the
prostate cancer outcomes study.
AB - BACKGROUND: To assess the relationship between androgen deprivation therapy (ADT)
exposure and self-reported bone complications among men in a population-based
cohort of prostate cancer survivors followed for 15 years after diagnosis.
METHODS: The Prostate Cancer Outcomes Study enrolled 3533 patients diagnosed with
prostate cancer between 1994 and 1995. This analysis included participants with
non-metastatic disease at the time of diagnosis who completed 15-year follow-up
surveys to report development of fracture, and use of bone-related medications.
The relationship between ADT duration and bone complications was assessed using
multivariable logistic regression models. RESULTS: Among 961 surviving men, 157
(16.3%) received prolonged ADT (>1 year), 120 (12.5%) received short-term ADT (?
1 year) and 684 (71.2%) did not receive ADT. Men receiving prolonged ADT had
higher odds of fracture (OR 2.5; 95% confidence interval (CI): 1.1-5.7), bone
mineral density testing (OR 5.9; 95% CI: 3.0-12) and bone medication use (OR 4.3;
95% CI: 2.3-8.0) than untreated men. Men receiving short-term ADT reported rates
of fracture similar to untreated men. Half of men treated with prolonged ADT
reported bone medication use. CONCLUSIONS: In this population-based cohort study
with long-term follow-up, prolonged ADT use was associated with substantial risks
of fracture, whereas short-term use was not. This information should be
considered when weighing the advantages and disadvantages of ADT in men with
prostate cancer.
PMID- 25134941
TI - The role of the bipolar plasmakinetic TURP over 100 g prostate in the elderly
patients.
AB - BACKGROUND AND PURPOSE: Bipolar plasma kinetic (BP) transurethral resection of
prostate (TURP) has been proved to be a safe and effective treatment for benign
prostatic enlargement (BPE). However, the role of bipolar TURP on large prostates
over 100 g compared with open suprapubic prostatectomy (SP) in elderly patients
(>65 years) has not ever been studied before. PATIENTS AND METHODS: A
retrospective analysis of patients' medical records between 2007 and 2012 was
performed. A total of 102 patients who underwent SP (n = 44) or BP-TURP [Gyrus
Plasma KineticTM (Gyrus ACMI, USA)] (n = 58) for obstructive lower urinary tract
symptoms due to BPE were included in this retrospective study. Inclusion criteria
were age >=65 years, prostate volume >=100 g, International Prostate Symptom
Score (IPSS) >=18, and peak urinary flow rate (PFR) <=15 ml/s. Exclusion criteria
were urethral stricture, known history of neurogenic bladder due to neural
disorders, previous prostate and/or urethral surgery, bladder stone, bladder
cancer, and known prostate cancer. Operation time, hospitalization, and catheter
removal times were noted. Patients were re-evaluated at postoperative 3rd and
12th months. Evaluated parameters were IPSS, quality of life (QoL), simplified
International Index of Erectile Function-5 (IIEF-5), PFR, post-voiding residual
urinary volume (PVR). Statistical significance was set at 0.05 and all tests were
two-tailed. RESULTS: Preoperative IPSS, PVR, IIEF-5, QoL, and prostate volume
were not statistically significantly different between two groups except for PFR.
Mean follow-up for BP-TURP and SP groups were 15.0 +/- 5.8 (R: 11-38), 22.1 +/-
11.2 (R: 11-59) months, respectively (p < 0.001). When compared with SP, mean
catheter removal time (p < 0.001) and median hospitalization time (p < 0.001)
were significantly shorter in BP-TURP group. However, mean operative time was
significantly (p < 0.001) longer than SP group and also median resected material
weight was significantly lower in the BP-TURP group (p < 0.001). IPSS, QoL, PFR,
PVR, and IIEF-5 scores at postoperative 3rd and 12th month were not significantly
different between the two groups (p > 0.05). Thirty-three patients had
perioperative complications according to the modified Clavien-Dindo system.
Thirteen patients (22.4 %) in BP-TURP group and 20 patients (45.4 %) in SP group
had complications. In 12th month follow-up visit, four patients presented with
urethral stricture, three patients (5.1 %) were in BP-TURP group, and one patient
(2.3 %) in SP group (p = 0.455). All strictures were treated with internal
urethrotomy. CONCLUSIONS: BP-TURP is a safe and highly effective treatment
modality for BPE in the elderly patients with prostate glands over 100 g.
Clinical efficacy and postoperative 12th month's results were similar to SP.
Larger studies with longer follow-up are needed in order to confirm our findings.
PMID- 25134942
TI - Relationship between prehypertension and incidence of chronic kidney disease in a
general population: a prospective analysis in central south China.
AB - OBJECTIVE: The objective of the study was to investigate whether prehypertension
is associated with progression to chronic kidney disease (CKD) in the general
population in central south China. METHODS: A prospective cohort study was
carried out in 1,703 white-collar workers without preexisting CKD in Changsha in
2006 at baseline. The cohort population was followed for an average of 54 months
by annual examinations. The glomerular filtration rate (GFR) was estimated using
the Modification of Diet in Renal Disease study equation modified by the Chinese
coefficient. CKD was defined as positive albuminuria or an estimated GFR <60
mL/min/1.73 m(2). Blood pressure (BP) categories were defined by the Seventh
Report of the Joint National Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure. The association of blood pressure and CKD
incidence was examined using a Cox regression model adjusted for relevant
factors. RESULTS: During the follow-up of cohort, 194 incidences of CKD were
recorded. Compared with normotension group, the hazard ratios (95 % confidential
intervals) for CKD were 1.25 (1.02-1.85) in prehypertension group, 1.62 (1.07
2.79) in undiagnosed hypertension group, and 1.98 (1.15-3.96) in diagnosed
hypertension group. Kaplan-Meier curves showed there was a significant difference
in the cumulative incidence of CKD between the different blood pressure
categories (log-rank test, P < 0.001). The independent risk factors of CKD were
age, estimated glomerular filtration rate (eGFR), systolic blood pressure, and
diastolic blood pressure according to the Cox proportional hazard analysis. It
was found that 2.4 % in participants with CKD incidences could be described as
excessive incidence attributable to prehypertension. CONCLUSION: Prehypertension
is significantly associated with CKD in a Chinese urban population.
PMID- 25134943
TI - Does the nephrostomy tract length impact the outcomes of percutaneous
nephrolithotomy (PNL)?
AB - PURPOSE: Different factors can determine the outcomes of percutaneous
nephrolithotomy (PNL). We analyzed the effect of tract length (TL) on outcomes
after PNL. METHODS: We performed a retrospective review of patients undergoing
PNL between 2006 and 2011. Patients with preoperative computed tomography (CT),
one percutaneous access tract and follow-up imaging within 3 months were
included. TL was defined as distance between the skin to the calyx of puncture as
measured on preoperative CT. Measurements were independently performed by two
urologists and the average was used for analysis. Stone-free rate (SFR) was
defined as zero fragments on follow-up imaging. Factors independently associated
with the likelihood of being stone-free after PNL were determined using
multivariable analysis adjusted for TL, location of access, the presence of
incomplete or complete staghorn calculi and type of follow-up imaging.
Complications (Clavien score) were independently assessed. RESULTS: A total of
222 patients were included. Median stone burden and body mass index (BMI) was
239.4 mm(2) and 30.5 [interquartile range (IQR): 25.7-36.2]. The median TL was
85.0 mm (IQR: 70.3-100.0) and highly correlated with BMI (rho = 0.66, p < 0.001).
A total of 101 patients (45.5 %) were stone-free. TL was not associated with SFR
(p = 0.53). Clavien 1 and 2 complications occurred in 38 (17 %) while Clavien 3
and 4 complications occurred in 17 (8 %) patients. Multivariable analysis
revealed no association between complications and TL even when adjusted for
gender. CONCLUSIONS: Percutaneous TL is not associated with outcomes of PNL. PNL
is a safe and effective treatment for stones in patients with differing body
habitus.
PMID- 25134944
TI - Open reconstruction of recurrent vesicourethral anastomotic stricture after
radical prostatectomy.
AB - OBJECTIVES: To determine the outcomes of open vesicourethral anastomotic
reconstruction (VUAR) for outlet stenosis following radical prostatectomy (RP).
METHODS: Review of all cases of VUAR within an IRB-approved database was
performed. Preoperative factors assessed included cancer treatment modality,
duration of symptoms, prior treatments, and length of defect. Outcomes reviewed
included length-of-stay (LOS), complications, maintenance of patency, continence,
and need for additional procedures. RESULTS: Twelve cases of VUAR performed by a
single surgeon (BJF) from 2004 to 2012 were identified. Surgical approaches were
either abdominal (7), perineal (3), or abdominoperineal (2). All patients
underwent prior RP, with 25 % having subsequent radiotherapy. Among patients with
stenosis, 43 % were completely obliterated. Two cases had prior anastomotic
disruption in the early postoperative period after RP. The median length of
stenosis was 2.5 cm (range 1-5 cm) and median LOS was 3.0 days (range 1-7 days).
At a median follow-up of 75.5 months (range 14-120 months), 92 % of men retained
patency; only 25 % were continent. CONCLUSION: In experienced hands, VUAR can
restore durable patency for men afflicted with outlet stenosis after RP. Despite
anatomic restoration, incontinence is likely.
PMID- 25134945
TI - From extraordinary endocytobionts to pandoraviruses. Comment on Scheid et al.:
Some secrets are revealed: parasitic keratitis amoebae as vectors of the scarcely
described pandoraviruses to humans.
PMID- 25134946
TI - Isolation and molecular characterization of Acanthamoeba and Balamuthia
mandrillaris from combination shower units in Costa Rica.
AB - Free living amoebae (FLA) are ubiquitous protozoa, which may behave as parasites
under certain conditions. Four genera are recognized as causal agents of
infections in humans and animals: Naegleria, Sappinia, Acanthamoeba and
Balamuthia. This work determines the presence of FLA in combination shower units
and employs molecular biology for the characterization of isolates. The
morphological analysis and partial sequencing of the 18S rDNA gene revealed the
presence of Acanthamoeba genotype T4 in 30% of the units sampled. In addition to
Acanthamoeba cysts, trophozoites with morphological characteristics similar to
Balamuthia were identified. PCR assay using the mitochondrial 16S rRNA gene as a
target confirmed the identification of the amoeba as Balamuthia mandrillaris. Up
to date, this is the first report of the isolation of B. mandrillaris in Central
America and the fifth report worldwide.
PMID- 25134947
TI - Harmonisation of short-term in vitro culture for the expansion of antigen
specific CD8(+) T cells with detection by ELISPOT and HLA-multimer staining.
AB - Ex vivo ELISPOT and multimer staining are well-established tests for the
assessment of antigen-specific T cells. Many laboratories are now using a period
of in vitro stimulation (IVS) to enhance detection. Here, we report the findings
of a multi-centre panel organised by the Association for Cancer Immunotherapy
Immunoguiding Program to investigate the impact of IVS protocols on the detection
of antigen-specific T cells of varying ex vivo frequency. Five centres performed
ELISPOT and multimer staining on centrally prepared PBMCs from 3 donors, both ex
vivo and following IVS. A harmonised IVS protocol was designed based on the best
performing protocol(s), which was then evaluated in a second phase on 2 donors by
6 centres. All centres were able to reliably detect antigen-specific T cells of
high/intermediate frequency both ex vivo (Phase I) and post-IVS (Phase I and II).
The highest frequencies of antigen-specific T cells ex vivo were mirrored in the
frequencies following IVS and in the detection rates. However, antigen-specific T
cells of a low/undetectable frequency ex vivo were not reproducibly detected post
IVS. Harmonisation of the IVS protocol reduced the inter-laboratory variation
observed for ELISPOT and multimer analyses by approximately 20 %. We further
demonstrate that results from ELISPOT and multimer staining correlated after (P <
0.0001 and R (2) = 0.5113), but not before IVS. In summary, IVS was shown to be a
reproducible method that benefitted from method harmonisation.
PMID- 25134948
TI - Effect of organic solvents on the structure and activity of moderately halophilic
Bacillus sp. EMB9 protease.
AB - Halophilic enzymes have been manifested for their stability and catalytic
abilities under harsh operational conditions. These have been documented to
withstand denaturation in presence of high temperature, pH, presence of organic
solvents and chaotropic agents. The present study aims at understanding the
stability and activity of a halophilic Bacillus sp. EMB9 protease in organic
solvents. The protease was uniquely stable in polar solvents. A clear correlation
was evident between the protease function and conformational transitions,
validated by CD and fluorescence spectral studies. The study affirms that
preservation of protein structure, possibly due to charge screening of the
protein surface by Ca(2+) and Na(+) ions provides stability against organic
solvents and averts denaturation. Salt was also found to exert a protective
effect on dialyzed protease against chaotropism of solvents. Presence of 1 %
(w/v) NaCl restored the activity in the dialyzed protease and prevented
denaturation in methanol, toluene and n-decane. The work will have further
implication on discerning protein folding in saline as well as non-aqueous
environments.
PMID- 25134949
TI - Competing priorities: staff perspectives on supporting recovery.
AB - Recovery has come to mean living a life beyond mental illness, and recovery
orientation is policy in many countries. The aims of this study were to
investigate what staff say they do to support recovery and to identify what they
perceive as barriers and facilitators associated with providing recovery-oriented
support. Data collection included ten focus groups with multidisciplinary
clinicians (n = 34) and team leaders (n = 31), and individual interviews with
clinicians (n = 18), team leaders (n = 6) and senior managers (n = 8). The
identified core category was Competing Priorities, with staff identifying
conflicting system priorities that influence how recovery-oriented practice is
implemented. Three sub-categories were: Health Process Priorities, Business
Priorities, and Staff Role Perception. Efforts to transform services towards a
recovery orientation require a whole-systems approach.
PMID- 25134950
TI - Evaluation of Period of PURPLE Crying, an abusive head trauma prevention program.
AB - The Period of PURPLE Crying program is used to educate parents and caregivers
about normal infant crying and the dangers of infant shaking. We evaluated nurse
led, hospital-based implementation of the program using a nonexperimental,
posttest-only design. New mothers rated the program as useful, and the program
was effective in teaching mothers about normal infant crying, the dangers of
infant shaking, and soothing and coping techniques. The findings support the
feasibility and need for broad dissemination of the program.
PMID- 25134952
TI - Comparative study of the selective degradations of two enantiomers in the
racemate and an enriched concentration of indoxacarb in soils.
AB - In this study, selective degradations of the two enantiomers of indoxacarb in the
concentrate (2.33S/1R) and racemate (1S/1R) are examined. The absolute
configurations of indoxacarb enantiomers were determined using X-ray diffraction.
The results showed that in two alkaline soils, the S-(+)-indoxacarb was
preferentially degraded in both the concentrate and racemate. In one acid soil,
the two enantiomers degraded no-selectivity. In another acid soil and one neutral
soil, the R-(-)-indoxacarb was preferentially degraded in both the concentrate
and racemate. Indoxacarb enantiomers were configurationally stable in the five
soils, and no interconversion was observed during the incubation. Because no
significant difference in degradation was observed after samples were sterilized,
the observed enantioselectivity may be attributed primarily to microbial activity
in soils. The results indicate that the selective degradation behavior was the
same for both formulations that were tested.
PMID- 25134951
TI - Multidisciplinary intensive education in the hospital improves outcomes for
hospitalized heart failure patients in a Japanese rural setting.
AB - BACKGROUND: Heart failure (HF) patients living in rural areas have a lack of HF
knowledge and poor self-care because of limited medical care access.
Multidisciplinary education to improve self-care behavior is indispensable for
such patients. The present study evaluated whether intensive inpatient education
improved outcomes of hospitalized HF patients in a Japanese rural setting.
METHODS: An inpatient HF management program based on multidisciplinary team
intervention was applied to hospitalized HF patients in a Japanese rural area. We
defined patients treated within the program from May 2009 to April 2011 as the
intervention group (n = 144), and those treated with the usual care from May 2006
to April 2009 as the usual care group (n = 133). The composite endpoints of HF
hospitalization and all-cause mortality were compared between the two groups.
RESULTS: Compared with patients in the usual care group, those in the
intervention group more often received the optimal interventions such as
discharge use of beta-blockers, cardiac rehabilitation, pre-discharge diagnostic
tests, and multidisciplinary intensive education including nurse-led patient
education, pharmacist's medication teaching, and dietitian's nutritional guidance
(all P < 0.05). The incidence of the composite endpoints significantly decreased
after introducing the program (P < 0.001). Among a number of interventions,
multidisciplinary intensive education was the most effective intervention to
improve the primary outcome (P < 0.001). CONCLUSIONS: Multidisciplinary intensive
education is a key strategy for helping improve the outcome for Japanese HF
patients in a rural setting. Our data may give a positive impact on the
improvement of healthcare system in Japan.
PMID- 25134953
TI - Drug-coated balloon angioplasty for drug-eluting stent restenosis: insight from
randomized controlled trials.
AB - BACKGROUND: The best treatment option for drug-eluting stent (DES) restenosis has
not been established. We performed a meta-analysis to assess the clinical
efficacy of drug-coated balloon (DCB) for the treatment of DES restenosis.
METHODS: Trials were identified through a literature search from January 2005
through April 2014. All randomized controlled trials were eligible for inclusion
if they compared DCB with a control treatment (plain old balloon angioplasty
[POBA] or DES) in patients with DES restenosis. RESULTS: Five studies and a total
of 864 patients were included in this analysis. Most end-points were
significantly reduced for DCB compared with the control groups. For major adverse
cardiac events, the relative risk (RR) was 0.49 (P = 0.012); for target lesion
revascularization, it was 0.50 (P = 0.044); for recurrent restenosis, it was 0.41
(P = 0.002). There was a lower mortality for DCB (RR 0.29; P = 0.017). The
incidence of myocardial infarction was numerically lower, but without statistical
significance (RR 0.76; P = 0.55). The DCB effect was more pronounced when
compared with POBA than when compared with DES. CONCLUSIONS: This meta-analysis
showed that DCB was superior to POBA and comparable to DES for treatment of DES
restenosis. The findings in this meta-analysis cannot be extrapolated to DCB in
general, because all DCB used in trials included was a single brand of paclitaxel
coated balloon.
PMID- 25134955
TI - New evidence on the relationship between Microsporidia and Fungi: a genome-wide
analysis by DarkHorse software.
AB - Microsporidia are a group of obligate intracellular eukaryotic parasites that
infect a wide variety of species, including humans. Phylogenetic analysis
indicates a relationship between the Microsporidia and the Fungi. However, most
results are based on the analysis of relatively few genes. DarkHorse analysis
involves the transformation of BLAST results into a lineage probability index
(LPI) value and allows for the comparison of genes for an entire genome with
those of other genomes. Thus, we can see which genes from the microsporidia score
most closely based on the LPI with other eukaryotic organisms. In this analysis,
we calculated the LPI for each gene from the genomes of 7 Microsporidia,
Antonospora locustae, Enterocytozoon bieneusi, Encephalitozoon cuniculi,
Encephalitozoon intestinalis, Nosema bombycis, Nosema ceranae, and Nematocida
parisii, to analyze the genetic relationships between Microsporidia and other
species. It was found that many (91%) genes were most closely correlated with
genes from other microsporidial genomes and had the highest mean LPI (0.985),
indicating a monophyletic origin of the Microsporidia. In a subsequent analysis,
we excluded the other Microsporidia from the analysis to look for relationships
before the divergence of Microsporidia, and found that 43% of the microsporidial
genes scored highest with fungal genes, and a higher mean LPI was found with
Fungi than with other kingdoms, suggesting that Microsporidia is closely related
to Fungi at the genomic level. Microsporidial genes were functionally clustered
based on the KOG (Eukaryotic COG) database, and the possible lineages for each
gene family were discussed in concert with the DarkHorse results.
PMID- 25134954
TI - Effects of glucagon-like peptide-1 agents on left ventricular function:
systematic review and meta-analysis.
AB - BACKGROUND: The cardiovascular safety of many glucagon-like peptide-1 agents (GLP
1 agents) is unclear. In this study, we assess the effects of the GLP-1 agents on
left ventricular function in patients with type 2 diabetes (T2DM) and/or
cardiovascular disease (CVD). METHODS: PubMed, EMBASE, and the Cochrane Library
were searched for the relevant publications up to May 2013 without restriction by
language. All clinical controlled trials assessing left ventricular function and
cardiovascular outcomes with the GLP-1 agents were selected for eligibility.
Fourteen trials (415 patients) were identified as eligible between 1966 and 2013.
Twelve of the studies were randomized controlled trials (RCT). RESULTS: The
results showed that GLP-1 agent treatment in patients with T2DM and/or CVD led to
significantly improved regional left ventricular contractile parameters
(including peak left systolic tissue velocity and strain) and global left
ventricular performance (including stroke volume, ejection fraction, and left
ventricular chambers) compared with patients receiving placebo. CONCLUSIONS: GLP
1 agent treatment in T2DM and/or CVD patients is associated with a modest but
significant increase in the odds of left ventricular contractile parameters and
left ventricular performance compared with patients having received placebo,
which may be indicative of additional cardiovascular benefits for these patients.
PMID- 25134956
TI - Microbial contamination of power toothbrushes: a comparison of solid-head versus
hollow-head designs.
AB - PURPOSE: Microbial contamination of manual toothbrushes relative to their design
has been documented for decades, citing concern for cross contamination and self
infection with microorganisms. A pilot study of different power toothbrushes was
conducted, to compare a solid-head brush to 2 hollow-head brushes for residual
contamination with commonly occurring oral microorganisms. METHODS: Participants
who met inclusion criteria were enrolled and brushed twice daily for 3 weeks with
1 of 3 randomly assigned power toothbrushes. Brush heads were vortexed and
cultured using 5 appropriate media for oral microorganisms: anaerobes and
facultative microorganisms, yeast and mold, oral streptococci and oral
enterococci anaerobes, Porphyromonas gingivalis, and Fusobacterium species.
Analysis of covariance was used to compare the brush groups for transformed
microbial counts after adjusting for any demographic variables that may have
confounded the results. RESULTS: The solid-head power toothbrush was found to
have significantly less microbial contamination than either of the 2 hollow-head
power toothbrushes for all the bacteria tested and less than 1 of the hollow-head
brushes for yeast and mold. CONCLUSION: The solid-head power toothbrush studied
had significantly less residual microbial contamination than the 2 hollow-head
power toothbrushes after 3 weeks of twice daily brushing with non-antimicrobial
toothpaste.
PMID- 25134957
TI - The use of social media in dental hygiene programs: a survey of program
directors.
AB - PURPOSE: The use of social media and social networking sites has become
increasingly common by the current generation of students. Colleges and
universities are using social media and social networking sites to advertise,
engage and recruit prospective students. The purpose of this study was to
evaluate how social media is being used in dental hygiene program admissions and
policy. METHODS: Researchers developed a survey instrument investigating the use
of social media. The survey included questions about demographic information,
personal use of social media, program use of social media, social media use in
admissions and social media policies. An email was sent to 321 dental hygiene
program directors asking them to complete the survey. All participants were
provided 4 weeks to complete the survey, and 2 reminder emails were sent.
RESULTS: A total of 155 responses were received (48.3% response rate). While 84%
of respondents indicated their program had a web page, only 20% had an official
Facebook page for the program and 2% had a Twitter page. Thirty-five percent had
a program policy specifically addressing the use of social media and 31%
indicated that their university or institution had a policy. Only 4% of programs
evaluate a potential student's Internet presence, mostly by searching on
Facebook. Statistically significant differences (p<=0.05) were noted between
those respondents with more personal social media accounts and those with fewer
accounts, as those with more accounts were more likely to evaluate a potential
student's Internet presence. Open ended responses included concern about social
media issues, but some uncertainty on how to handle social media in the program.
The concern for social media and professionalism was evident and more research
and discussion in this area is warranted. CONCLUSION: Social media is currently
being used in a variety of ways in dental hygiene programs, but not in the area
of admissions. There is some uncertainty about the role social media should play
in a professional environment.
PMID- 25134958
TI - Smiles over time: an older adult oral health survey in Illinois.
AB - PURPOSE: The purpose of the project was to identify the oral health status and
needs of the older adult population >=60 years old in Illinois for policy
decisions and to help identify possible need for oral health interventions. No
baseline data has previously been collected on this population in Illinois.
METHODS: A public/private collaboration was formed, which included the Illinois
Department of Public Health, the IFLOSS Coalition and dental and dental hygiene
schools in Illinois. The screening tool was developed based on methods outlined
by Association of State and Territorial Dental Directors for Basic Screening
Surveys. Questionnaires and in-mouth screenings were conducted at selected sites
statewide. Data was collected by dental and dental hygiene students and faculty
at onsite clinics and community outreach sites. RESULTS: A total of 437 seniors
were screened statewide. Of this population, 81% had no dental insurance, 13%
were edentulous and 58% claimed to have had a dental visit in the last year.A
total of 26% rated their oral health as fair or poor, while 29% had untreated
caries. Suspicious oral lesions were present in 14% (n=308 for the oral lesions
indicator), 19% needed immediate dental care and 41% required referral.
CONCLUSION: This study revealed that surveillance can be accomplished by the
collaboration among entities with focus on a specific population. Additional
surveillance efforts are warranted among older adults in Illinois in an effort to
plan and to implement appropriate interventions for addressing the oral health
needs of this population.
PMID- 25134960
TI - Effects of motor-level transcutaneous electrical nerve stimulation on ipsilateral
and un-stimulated contralateral quadriceps femoris.
AB - PURPOSE: There is a paucity of data on effects of motor-level stimulation using
Transcutaneous Electrical Nerve Stimulator (TENS) on ipsilateral quadriceps
femoris group of muscles. The effect is also unknown on the untrained
contralateral quadriceps femoris. The primary purpose of this study was to
determine the effect of TENS on quadriceps muscle strength at the stimulated
ipsilateral and un-stimulated contra-lateral extremities. METHODS: Participants
were 50 apparently healthy undergraduate. They were recruited using sample of
convenience. The right quadriceps group of muscles were stimulated for 15 minutes
twice a week for 8 weeks using motor-level stimulation parameters (frequency of
85 Hz and pulse width of 100 microseconds) while the left lower limbs (control)
were not stimulated. The right and left quadriceps muscle strengths were
quantified using tensiometer; at onset and after 8 weeks. The data were analysed
using the descriptive and inferential statistics (paired t-test and ANOVA). Alpha
level was set at 0.05. RESULTS: The initial and final left strengths of the un
stimulated quadriceps muscles were 311.46 +/- 58.84N and 395.60 +/- 100.71N at
onset and after 8 weeks respectively. After 8 weeks the un-stimulated left
quadriceps strength was significantly greater than the initial value (t=-7.63, p
< 0.001). Similarly, the initial and final right quadriceps strength (stimulated
limb) were 351.51 +/- 117.68N and 471.31 +/- 112.19N; at onset and after 8 weeks
respectively. The post stimulation strength of the right quadriceps was also
significantly higher than the pre-intervention strength (t=-10.25, p < 0.001).
However, the increment in quadriceps strength between right and left extremities
after 8 weeks was insignificant (t =-1.35, p=0.18). There was also significant
increase in the girth of the right quadriceps (t= -6.08, p=0.001) after 8 weeks.
CONCLUSION: We concluded that there were increments in both strength and muscle
size of the stimulated right quadriceps using motor level stimulation parameters
of TENS modality. The un-stimulated contralateral quadriceps strength also
increased after 8 weeks. This implied that there was cross-training effect at the
contralateral quadriceps group of muscles.
PMID- 25134959
TI - Identification of drug-resistant Salmonella from food handlers at the University
of Gondar, Ethiopia.
AB - BACKGROUND: Salmonella species are among the most common food borne pathogens
worldwide and their infection is one of the major global public health problems.
During the last decade, multidrug-resistant Salmonella species have increased to
a great deal, especially in developing countries. The prevalence and
antimicrobial susceptibility pattern of Salmonella isolates among food handlers
at the University of Gondar, Ethiopia, were described in the current
investigation. METHOD: A cross-sectional study was conducted from February to
June, 2013 at the University of Gondar. Stool samples from selected volunteer
food handlers were collected and analyzed complemented with questionnaire.
Standard isolation, identification and biochemical tests were performed to
identify Salmonella isolates. Antimicrobial susceptibility tests were also
carried out on each isolate using Kirby-Bauer disc diffusion method. The data was
entered into Epi info version 3.5.4 and analyzed using SPSS version 21. RESULT:
Out of 423 food handlers participated, 303(71.6%) were females. Almost two-third
(71.4%) of food handlers had no previous medical checkup to Salmonella infection
and only 24(5.7%) of them were certified as food handlers. Thirteen (3.1%) food
handlers were found to be positive for Salmonella isolates. The results of
antimicrobial susceptibility test in the current research revealed that from a
total of 13 isolates; 9(69.2%), 8(61.5%), 6(46.2%) and 6(46.2%) of the isolates
were resistant to amoxicillin, ampicillin, nitrofurantoin and tetracycline,
respectively. In addition, nearly half (46.2%) of the isolates were multidrug
resistant. However; all of them were sensitive for both ceftriaxone and
gentamycin. CONCLUSION: This study indicated that drug resistant including
multidrug-resistant Salmonella isolates were circulating among food handlers at
the University of Gondar. These Salmonella positive food handlers pose
significant risk of infection to the university community particularly to the
student population. It is essential to implement food handlers training on food
safety, conduct periodic medical screening and continuous monitoring of food
handlers at the study university.
PMID- 25134961
TI - Diagnostic value of bone scintigraphy for aseptic loosening after total knee
arthroplasty.
AB - BACKGROUND: Despite technical improvements, aseptic loosening after total knee
arthroplasty (TKA) remains a frequent complication. A one-stage revision
arthroplasty is the most common therapeutic pathway. OBJECTIVE: The aim of this
study was to evaluate the diagnostic value of bone scintigraphy in detecting
aseptic loosening after TKA. METHODS: We retrospectively identified 46 cases of
one-stage revision TKA performed between January 2011 and December 2012. In each
case a bone scintigraphy was performed at least one year after the primary TKA
and 3.2 +/- 2.2 month prior to revision arthroplasty. Additionally, we evaluated
the rate of satisfaction and pain level 16.2 +/- 5.4 months after one-stage
revision arthroplasty. RESULTS: Bone scintigraphy indicated aseptic loosening in
28 cases. Intraoperative aseptic loosening was verified in 34 cases. Bone
scintigraphy had a sensitivity of 0.76 and a specificity of 0.83 in detecting
aseptic loosening. The positive predictive value was 0.93, and the negative
predictive value 0.56. At follow-up consultation, 35 patients were very satisfied
or satisfied, and 31 patients had no pain or occasional pain. CONCLUSIONS: Bone
scintigraphy is a helpful tool in detecting aseptic loosening after TKA.
Nevertheless, the results from bone scintigraphy should be compared with clinical
findings and patients' disorders.
PMID- 25134962
TI - A review on the technologies and services used in the self-management of health
and independent living of elderly.
AB - As the number of aged people is rapidly growing, the need for health and living
care of aged people living alone becomes imperative. The telecare systems are
able to provide flexible services for older people suffering from chronic
diseases, but are largely user group oriented. However, it is common in elderly
to show symptoms of a combination of (chronic) diseases. Moreover, elderly are
totally dependent on a third person as they are unable to perform a number of
basic functions at home. They also feel cutt off from the social fabric. Old
people living in remote places typically use telephone that dials a social alarm
control center or mobile social alarm systems and monitoring systems. This study
examines the existing solutions related to elderly assistance and proposes an
advanced solution based on web technology for the self-management of health and
independent living of elderly.
PMID- 25134963
TI - Nanomechanical characterization of exfoliated and retained deciduous incisors.
AB - OBJECTIVES: The anisotropic natures of dental tissues result in variable
properties from one point to the other within the same tooth. The aim of this
study was to analyze deciduous incisors enamel and dentin for elastic modulus and
hardness. In addition, retained deciduous incisors were assessed to compare
properties with exfoliated teeth. METHODS: Deciduous mandibular incisors either
exfoliated at physiological age or retained were included in this study. Samples
were prepared by dissecting teeth in transverse sections and surfaces under
investigation were prepared and polished for nanoindentation. Nanoindentation was
performed at multiple sites using Hysitron [TI 725 Ubi] testing instrument. Data
analysis was performed using SPSS software (version 20) to calculate absolute
hardness and elastic modulus. The statistical significance was calculated using
the t-test. RESULTS: The hardness of human deciduous incisor varies between 0.01
7 GPa. The highest value of hardness was observed for the incisal edge (5.09 +/-
0.64 GPa) followed by mid-surface enamel and cervical enamel. The hardness of
mantle dentin was (0.56 +/- 0.19 GPa) and the inner dentin was (0.34 +/- 0.12
GPa). CONCLUSIONS: The average hardness of primary teeth enamel is lower than
permanent teeth enamel. The hardness of retained teeth enamel is greater than
exfoliated teeth however lower than permanent teeth enamel of the equivalent
region.
PMID- 25134964
TI - Correlation study in respiration fluctuations during sleep stages.
AB - BACKGROUND: Healthy sleep can be characterized by several stages: wake, light,
SWS, and REM sleep. The clinical experts find that the breath of subjects is
different in these sleep stages, but such observation is lacking data supporting,
The statistical research about investigating breathing patterns during sleep
process will be helpful for the sleep and breathing domain. OBJECTIVE: The
objective of the paper is to statistically analyze the respiratory
characteristics during different sleep stages. METHODS: Firstly, we calculated
the mean value and standard deviation of respiratory rates of these stages, in
which the respiratory rates were obtained by the autocorrelation method. Then the
detrended fluctuation analysis (DFA) algorithm was applied to analyze long-range
correlation of respiratory rates of sleep stages. RESULTS: The mean and standard
deviation of respiratory rates are wake: 16.62 +/- 2.43 cycles per minute (CPM),
light: 15.15 +/- 1.53 CPM, SWS: 15.06 +/- 0.96 CPM and REM: 16.37 +/- 2.03 CPM,
respectively. The scaling exponent applied by detrended fluctuation analysis
(DFA) algorithm reached about 0.7 for each stage. CONCLUSION: Results of the mean
and standard deviation of respiratory rates show that different sleep stages lead
to different autonomic regulations of breathing and exhibit different respiratory
rates and fluctuations. And the DFA results demonstrate that respiratory rates
are all long-range correlated in these stages although they lead to different
fluctuation.
PMID- 25134965
TI - In vitro and in vivo characterization of pentaerythritol triacrylate-co
trimethylolpropane nanocomposite scaffolds as potential bone augments and grafts.
AB - A thiol-acrylate-based copolymer synthesized via an amine-catalyzed Michael
addition was studied in vitro and in vivo to assess its potential as an in situ
polymerizing graft or augment in bone defect repair. The blends of hydroxyapatite
(HA) with pentaerythritol triacrylate-co-trimethylolpropane (PETA), cast as
solids or gas foamed as porous scaffolds, were evaluated in an effort to create a
biodegradable osteogenic material for use as a bone-void-filling augment.
Osteogenesis experiments were conducted with human adipose-derived mesenchymal
stromal cells (hASCs) to determine the ability of the material to serve as an
osteoinductive substrate. Poly(E-caprolactone) (PCL) composites PCL:HA (80:20)
(wt/wt%) served as the control scaffold, while the experimental scaffolds
included PETA:HA (100:0), (85:15), (80:20), and (75:25) composites (wt/wt%). The
results indicate that PETA:HA (80:20) foam composites had higher mechanical
strength than the corresponding porous PCL:HA (80:20) scaffolds made by thermo
precipitation method, and in the case of foamed composites, increasing HA content
directly correlated with increased yield strength. For cytotoxicity and
osteogenesis experiments, hASCs cultured for 21 days on PETA:HA scaffolds in
stromal medium displayed the greatest number of live cells compared with PCL:HA
composites. Moreover, hASCs cultured on foamed PETA:HA (80:20) scaffolds resulted
in the greatest mineralization, increased alkaline phosphatase (ALP) expression,
and the highest osteocalcin (OCN) expression after 21 days. Overall, the PETA:HA
(80:20) and PETA:HA (85:15) scaffolds, with 66.38% and 72.02% porosity,
respectively, had higher mechanical strength and cytocompatibility compared with
the PCL:HA control. The results of the 6-week in vivo biocompatibility study
using a posterior lumbar spinal fusion model demonstrate that PETA:HA can be
foamed in vivo without serious adverse effects at the surgical site.
Additionally, it was demonstrated that cells migrate into the interconnected pore
volume and are found within centers of ossification.
PMID- 25134967
TI - Total calcium-sensing receptor expression in circulating monocytes is increased
in rheumatoid arthritis patients with severe coronary artery calcification.
AB - INTRODUCTION: Human circulating monocytes express the calcium-sensing receptor
(CaSR) and are involved in atherosclerosis. This study investigated the potential
association between vascular calcification in rheumatoid arthritis (RA) and CaSR
expression in circulating monocytes. METHODS: In this cross-sectional study, 50
RA patients were compared to 25 control subjects matched for age and gender.
Isolation of peripheral blood mononuclear cells and flow cytometry analysis were
performed to study the surface and total CaSR expression in circulating
monocytes. Coronary artery calcium (CAC) and abdominal aortic calcification (AAC)
scores were evaluated by computed tomography and an association between these
scores and the surface and/or total CaSR expression in circulating monocytes in
RA patients was investigated. RESULTS: The two groups were similar in terms of
age (RA: 60.9 +/- 8.3 years, versus controls: 59.6 +/- 5.3 years) and gender (RA:
74.0% females versus 72.0% females). We did not find a higher prevalence and
greater burden of CAC or AAC in RA patients versus age- and gender-matched
controls. When compared with control subjects, RA patients did not exhibit
greater total CaSR (101.6% +/- 28.8 vs. 99.9% +/- 22.0) or surface CaSR (104.6%
+/- 20.4 vs. 99.9% +/- 13.7) expression, but total CaSR expression in circulating
monocytes was significantly higher in RA patients with severe CAC (Agatston score
>= 200, n = 11) than in patients with mild-to-moderate CAC (1 to 199, n = 21) (P
= 0.01). CONCLUSIONS: This study demonstrates for the first time that total CaSR
expression in human circulating monocytes is increased in RA patients with severe
coronary artery calcification.
PMID- 25134966
TI - Relationship between post-cardiac arrest myocardial oxidative stress and
myocardial dysfunction in the rat.
AB - BACKGROUND: Reperfusion after resuscitation from cardiac arrest (CA) is an event
that increases reactive oxygen species production leading to oxidative stress.
More specifically, myocardial oxidative stress may play a role in the severity of
post-CA myocardial dysfunction. This study investigated the relationship between
myocardial oxidative stress and post-CA myocardial injury and dysfunction in a
rat model of CA and cardiopulmonary resuscitation (CPR). Ventricular fibrillation
was induced in 26 rats and was untreated for 6 min. CPR, including mechanical
chest compression, ventilation, and epinephrine, was then initiated and continued
for additional 6 min prior to defibrillations. Resuscitated animals were
sacrificed at two h (n = 9), 4 h (n = 6) and 72 h (n = 8) following
resuscitation, and plasma collected for assessment of: high sensitivity cardiac
troponin T (hs-cTnT), as marker of myocardial injury; isoprostanes (IsoP), as
marker of lipid peroxidation; and 8-hydroxyguanosine (8-OHG), as marker of DNA
oxidative damage. Hearts were also harvested for measurement of tissue IsoP and 8
OHG. Myocardial function was assessed by echocardiography at the corresponding
time points. Additional 8 rats were not subjected to CA and served as baseline
controls. RESULTS: Compared to baseline, left ventricular ejection fraction
(LVEF) was reduced at 2 and 4 h following resuscitation (p < 0.01), while it was
similar at 72 h. Inversely, plasma hs-cTnT increased, compared to baseline, at 2
and 4 h post-CA (p < 0.01), and then recovered at 72 h. Similarly, plasma and
myocardial tissue IsoP and 8-OHG levels increased at 2 and 4 h post-resuscitation
(p < 0.01 vs. baseline), while returned to baseline 72 h later. Myocardial IsoP
were directly related to hs-cTnT levels (r = 0.760, p < 0.01) and inversely
related to LVEF (r = -0.770, p < 0.01). Myocardial 8-OHG were also directly
related to hs-cTnT levels (r = 0.409, p < 0.05) and inversely related to LVEF (r
= -0.548, p < 0.01). CONCLUSIONS: The present study provides evidence that lipid
peroxidation and DNA oxidative damage in myocardial tissue are closely related to
myocardial injury and LV dysfunction during the initial hours following CA.
PMID- 25134968
TI - The prevalence of dementia subtypes in rural Tanzania.
AB - OBJECTIVES: The prevalence of dementia is predicted to increase rapidly in
developing countries. Vascular risk factors may contribute to this rise. Our aim
was to estimate the proportions of Alzheimer's disease (ADD) and vascular
dementia (VAD) in a prevalent cohort of dementia cases in rural Tanzania. DESIGN:
A two-stage door-to-door dementia prevalence study. SETTING: Hai district,
Tanzania PARTICIPANTS: In Phase I, the Community Screening Instrument for
Dementia (CSI-D) was used to screen 1198 community-dwelling people for dementia.
In Phase II, 168/184 (91.3%) of those with poor performance, 56/104 (53.8%) of
those with intermediate performance and 72/910 (7.9%) of those with good
performance on CSI-D were interviewed and diagnoses were made using the DSM-IV
criteria. MEASUREMENTS: For subtype diagnosis, DSM-IV dementia criteria plus
NINCDS-ADRDA criteria were used for ADD and NINDS-AIREN criteria for VAD. Other
dementias were diagnosed by international consensus criteria. Diagnoses were
confirmed or excluded by computerised tomography where clinically appropriate.
RESULTS: Of 78 dementia cases, 38 (48.7%) were ADD and 32 (41.0%) were VAD. The
crude prevalence of ADD was 3.7% (95% CI 2.5 to 4.9) and of VAD was 2.9% (95% CI
1.9 to 3.9). The age-adjusted prevalence was 3.0% (95% CI 1.8 to 4.2) for ADD and
2.6% (95% CI 1.6 to 3.6) for VAD. A previous diagnosis of diabetes mellitus was
independently associated with greater odds of having VAD than ADD. CONCLUSIONS:
VAD accounted for a greater proportion of dementia cases than expected. Further
investigation and treatment of risk factors is required in this setting.
PMID- 25134969
TI - Stimulation of suicidal erythrocyte death by sulforaphane.
AB - Sulforaphane, an isothiocyanate from cruciferous vegetable, counteracts
malignancy. The effect is at least in part due to the stimulation of suicidal
death or apoptosis of tumour cells. Mechanisms invoked in sulforaphane-induced
apoptosis include mitochondrial depolarization and altered gene expression.
Despite the lack of mitochondria and nuclei, erythrocytes may, similar to
apoptosis of nucleated cells, enter eryptosis, a suicidal cell death
characterized by cell shrinkage and phosphatidylserine translocation to the
erythrocyte surface. Stimulators of eryptosis include increase of cytosolic
Ca(2+)-activity ([Ca(2+)]i). This study explored whether sulforaphane stimulates
eryptosis. Cell volume was estimated from forward scatter, phosphatidylserine
exposure at the cell surface from annexin V binding and [Ca(2+)]i from Fluo-3
fluorescence. A 48-hr treatment of human erythrocytes with sulforaphane (50-100
MUM) significantly decreased forward scatter, significantly increased the
percentage of annexin V binding cells and significantly increased [Ca(2+)]i. The
effect of sulforaphane (100 MUM) on annexin V binding was significantly blunted
but not abrogated by the removal of extracellular Ca(2+). Sulforaphane (100 MUM)
significantly increased ceramide formation. In conclusion, sulforaphane
stimulates suicidal erythrocyte death or eryptosis, an effect at least partially,
but not exclusively, due to the stimulation of Ca(2+) entry and ceramide
formation.
PMID- 25134970
TI - Phenotyping polyclonal kappa and lambda light chain molecular mass distributions
in patient serum using mass spectrometry.
AB - We previously described a microLC-ESI-Q-TOF MS method for identifying monoclonal
immunoglobulins in serum and then tracking them over time using their accurate
molecular mass. Here we demonstrate how the same methodology can be used to
identify and characterize polyclonal immunoglobulins in serum. We establish that
two molecular mass distributions observed by microLC-ESI-Q-TOF MS are from
polyclonal kappa and lambda light chains using a combination of theoretical
molecular masses from gene sequence data and the analysis of commercially
available purified polyclonal IgG kappa and IgG lambda from normal human serum. A
linear regression comparison of kappa/lambda ratios for 74 serum samples (25
hypergammaglobulinemia, 24 hypogammaglobulinemia, 25 normal) determined by
microflowLC-ESI-Q-TOF MS and immunonephelometry had a slope of 1.37 and a
correlation coefficient of 0.639. In addition to providing kappa/lambda ratios,
the same microLC-ESI-Q-TOF MS analysis can determine the molecular mass for
oligoclonal light chains observed above the polyclonal background in patient
samples. In 2 patients with immune disorders and hypergammaglobulinemia, we
observed a skewed polyclonal molecular mass distribution which translated into
biased kappa/lambda ratios. Mass spectrometry provides a rapid and simple way to
combine the polyclonal kappa/lambda light chain abundance ratios with the
identification of dominant monoclonal as well as oligoclonal light chain
immunoglobulins. We anticipate that this approach to evaluating immunoglobulin
light chains will lead to improved understanding of immune deficiencies,
autoimmune diseases, and antibody responses.
PMID- 25134974
TI - Halogen bonds in crystal engineering: like hydrogen bonds yet different.
AB - The halogen bond is an attractive interaction in which an electrophilic halogen
atom approaches a negatively polarized species. Short halogen atom contacts in
crystals have been known for around 50 years. Such contacts are found in two
varieties: type I, which is symmetrical, and type II, which is bent. Both are
influenced by geometric and chemical considerations. Our research group has been
using halogen atom interactions as design elements in crystal engineering, for
nearly 30 years. These interactions include halogen...halogen interactions
(X...X) and halogen...heteroatom interactions (X...B). Many X...X and almost all
X...B contacts can be classified as halogen bonds. In this Account, we illustrate
examples of crystal engineering where one can build up from previous knowledge
with a focus that is provided by the modern definition of the halogen bond. We
also comment on the similarities and differences between halogen bonds and
hydrogen bonds. These interactions are similar because the protagonist atoms
halogen and hydrogen-are both electrophilic in nature. The interactions are
distinctive because the size of a halogen atom is of consequence when compared
with the atomic sizes of, for example, C, N, and O, unlike that of a hydrogen
atom. Conclusions may be drawn pertaining to the nature of X...X interactions
from the Cambridge Structural Database (CSD). There is a clear geometric and
chemical distinction between type I and type II, with only type II being halogen
bonds. Cl/Br isostructurality is explained based on a geometric model. In
parallel, experimental studies on 3,4-dichlorophenol and its congeners shed light
on the nature of halogen...halogen interactions and reveal the chemical
difference between Cl and Br. Variable temperature studies also show differences
between type I and type II contacts. In terms of crystal design, halogen bonds
offer a unique opportunity in the strength, atom size and interaction gradation;
this may be used in the design of ternary cocrystals. Structural modularity in
which an entire crystal structure is defined as a combination of modules is
rationalized on the basis of the intermediate strength of a halogen bond. The
specific directionality of the halogen bond makes it a good tool to achieve
orthogonality in molecular crystals. Mechanical properties can be tuned
systematically by varying these orthogonally oriented halogen...halogen
interactions. In a further development, halogen bonds are shown to play a
systematic role in organization of LSAMs (long range synthon aufbau module),
which are bigger structural units containing multiple synthons. With a formal
definition in place, this may be the right time to look at differences between
halogen bonds and hydrogen bonds and exploit them in more subtle ways in crystal
engineering.
PMID- 25134972
TI - Efficacy of dronedarone versus propafenone in the maintenance of sinus rhythm in
patients with atrial fibrillation after electrical cardioversion.
AB - PURPOSE: Our objective was to compare the efficacy of dronedarone and propafenone
in maintaining sinus rhythm in patients with atrial fibrillation (AF) after
electrical cardioversion. METHODS: In this single-center, open-label, randomized
trial, we randomly assigned patients with AF after electrical cardioversion to
receive dronedarone 400 mg BID or propafenone 150 mg TID. Follow-up clinical
evaluations were conducted at 1, 2, 3, and 6 months of treatment. The primary end
point was the time to the first recurrence of AF. FINDINGS: A total of 98
patients were enrolled (79 men; mean age, 59.2 years; n = 49 per group). The
median times to first recurrence of AF were 31 days in the dronedarone group and
32 days in the propafenone group (P = 0.715). The median (interquartile range)
ventricular rates at first recurrence of AF were 76.5 (67.3-86.5) beats/min in
the dronedarone group and 83.0 (71.0-96.0) beats/min in the propafenone group (P
= 0.059). IMPLICATIONS: Dronedarone and propafenone had similar efficacies in
maintaining sinus rhythm in patients with AF after electrical cardioversion. The
ventricular rate at the first recurrence of AF was numerically but not
statistically significantly lower in the dronedarone group than in the
propafenone group. ClinicalTrials.gov identifier: NCT01991119.
PMID- 25134973
TI - In vitro evaluation of the inhibitory effect of canine serum, canine fresh frozen
plasma, freeze-thaw-cycled plasma, and SolcoserylTM on matrix metalloproteinases
2 and 9.
AB - OBJECTIVE: Compare the efficacy of canine serum, fresh frozen plasma (FFP),
freeze-thaw-cycled plasma (FTCP), and Solcoseryl(TM) at inhibiting matrix
metalloproteinases (MMP) 2 and 9 in vitro. PROCEDURE: Matrix metalloproteinases 2
and 9 activity in the presence of serum, FFP, FTCP, or Solcoseryl(TM) was assayed
using a commercially available fluorogenic gelatinase activity kit. RESULTS:
Matrix metalloproteinases 2 activity in the presence of serum, FFP, FTCP, and
Solcoseryl(TM) was 20.84%, 5.76%, 8.10%, and 83.03%, respectively of uninhibited
MMP 2 activity. MMP 9 activity in the presence of serum, FFP, FTCP, and
Solcoseryl(TM) was 57.36%, 58.35%, 49.35%, and -8.69%, respectively of
uninhibited MMP 9 activity. CONCLUSION: Serum, FFP, and FTCP exhibit similar
levels of MMP 2 and 9 inhibitions. Solcoseryl(TM) causes minimal MMP 2
inhibition, but profound MMP 9 inhibition.
PMID- 25134971
TI - Sex differences in T cells in hypertension.
AB - PURPOSE: Hypertension is a major risk factor for cardiovascular disease, stroke,
and end-organ damage. There is a sex difference in blood pressure (BP) that
begins in adolescence and continues into adulthood, in which men have a higher
prevalence of hypertension compared with women until the sixth decade of life.
Less than 50% of hypertensive adults in the United States manage to control their
BP to recommended levels using current therapeutic options, and women are more
likely than are men to have uncontrolled high BP. This, is despite the facts that
more women compared with men are aware that they have hypertension and that women
are more likely to seek treatment for the disease. Novel therapeutic targets need
to be identified in both sexes to increase the percentage of hypertensive
individuals with controlled BP. The purpose of this article was to review the
available literature on the role of T cells in BP control in both sexes, and the
potential therapeutic application/implications of targeting immune cells in
hypertension. METHODS: A search of PubMed was conducted to determine the impact
of sex on T cell-mediated control of BP. The search terms included sex, gender,
estrogen, testosterone, inflammation, T cells, T regulatory cells, Th17 cells,
hypertension, and blood pressure. Additional data were included from our
laboratory examinations of cytokine expression in the kidneys of male and female
spontaneously hypertensive rats (SHRs) and differential gene expression in both
the renal cortex and mesenteric arterial bed of male and female SHRs. FINDINGS:
There is a growing scientific literature base regarding the role of T cells in
the pathogenesis of hypertension and BP control; however, the majority of these
studies have been performed exclusively in males, despite the fact that both men
and women develop hypertension. There is increasing evidence that although T
cells also mediate BP in females, there are distinct differences in both the T
cell profile and the functional impact of sex differences in T cells on
cardiovascular health, although more work is needed to better define the relative
impact of different T-cell subtypes on BP in both sexes. IMPLICATIONS: The
challenge now is to fully understand the molecular mechanisms by which the immune
system regulates BP and how the different components of the immune system
interact so that specific mechanisms can be targeted therapeutically without
compromising natural immune defenses.
PMID- 25134975
TI - Dimensionality control of d-orbital occupation in oxide superlattices.
AB - Manipulating the orbital state in a strongly correlated electron system is of
fundamental and technological importance for exploring and developing novel
electronic phases. Here, we report an unambiguous demonstration of orbital
occupancy control between t2g and eg multiplets in quasi-two-dimensional
transition metal oxide superlattices (SLs) composed of a Mott insulator LaCoO3
and a band insulator LaAlO3. As the LaCoO3 sublayer thickness approaches its
fundamental limit (i.e. one unit-cell-thick), the electronic state of the SLs
changed from a Mott insulator, in which both t2g and eg orbitals are partially
filled, to a band insulator by completely filling (emptying) the t2g (eg)
orbitals. We found the reduction of dimensionality has a profound effect on the
electronic structure evolution, which is, whereas, insensitive to the epitaxial
strain. The remarkable orbital controllability shown here offers a promising
pathway for novel applications such as catalysis and photovoltaics, where the
energy of d level is an essential parameter.
PMID- 25134976
TI - Dopamine D1 receptor availability is related to social behavior: a positron
emission tomography study.
AB - Dysfunctional interpersonal behavior is thought to underlie a wide spectrum of
psychiatric disorders; however, the neurobiological underpinnings of these
behavioral disturbances are poorly understood. Previous molecular imaging studies
have shown associations between striatal dopamine (DA) D2-receptor binding and
interpersonal traits, such as social conformity. The objective of this study was
to explore, for the first time, the role of DA D1-receptors (D1-Rs) in human
interpersonal behavior. Twenty-three healthy subjects were examined using
positron emission tomography and the radioligand [(11)C]SCH23390, yielding D1-R
binding potential values. Striatal D1-R binding was related to personality scales
selected to specifically assess one dimension of interpersonal behavior, namely a
combination of affiliation and dominance (i.e., the Social Desirability, Verbal
Trait Aggression and Physical Trait Aggression scales from Swedish Universities
Scales of Personality). An exploratory analysis was also performed for
extrastriatal brain regions. D1-R binding potential values in the limbic striatum
(r = .52; p = .015), associative striatum (r = .55; p = .009), and sensorimotor
striatum (r = .67; p = .001) were positively related to Social Desirability
scores. D1-R binding potential in the limbic striatum (r = -.51; p = .019) was
negatively associated with Physical Trait Aggression scores. For extrastriatal
regions, Social Desirability scores showed positive correlations in the amygdala
(r = .60; p = .006) and medial frontal cortex (r = .60; p = .004). This study
provides further support for the role of DA function in the expression of
disaffiliative and dominant traits. Specifically, D1-R availability may serve as
a marker for interpersonal behavior in humans. Associations were demonstrated for
the same dimension of interpersonal behavior as for D2-R, but in the opposite
direction, suggesting that the two receptor subtypes are involved in the same
behavioral processes, but with different functional roles.
PMID- 25134977
TI - Automated tract extraction via atlas based Adaptive Clustering.
AB - Advancements in imaging protocols such as the high angular resolution diffusion
weighted imaging (HARDI) and in tractography techniques are expected to cause an
increase in the tract-based analyses. Statistical analyses over white matter
tracts can contribute greatly towards understanding structural mechanisms of the
brain since tracts are representative of connectivity pathways. The main
challenge with tract-based studies is the extraction of the tracts of interest in
a consistent and comparable manner over a large group of individuals without
drawing the inclusion and exclusion regions of interest. In this work, we design
a framework for automated extraction of white matter tracts. The framework
introduces three main components, namely a connectivity based fiber
representation, a fiber bundle atlas, and a clustering approach called Adaptive
Clustering. The fiber representation relies on the connectivity signatures of
fibers to establish an easy correspondence between different subjects. A group
wise clustering of these fibers that are represented by the connectivity
signatures is then used to generate a fiber bundle atlas. Finally, Adaptive
Clustering incorporates the previously generated clustering atlas as a prior, to
cluster the fibers of a new subject automatically. Experiments on the HARDI scans
of healthy individuals acquired repeatedly, demonstrate the applicability,
reliability and the repeatability of our approach in extracting white matter
tracts. By alleviating the seed region selection and the inclusion/exclusion ROI
drawing requirements that are usually handled by trained radiologists, the
proposed framework expands the range of possible clinical applications and
establishes the ability to perform tract-based analyses with large samples.
PMID- 25134979
TI - Impact of comorbidity, age, and gender on seasonal variation in hip fracture
incidence. A NOREPOS study.
AB - Based on a total of 136,140 hip fractures, we found a distinct seasonal variation
in hip fracture incidence present in subgroups defined by age, gender, and
comorbidity. The seasonal variation was most pronounced in the youngest and the
healthiest patients. PURPOSE: The purpose of this study was to examine the
possible seasonal variation in hip fracture incidence in Norway by comorbidity,
age, and gender. METHODS: Data were retrieved from the NOREPOS Hip Fracture
Database containing all hip fractures in Norway during the time period 1994-2008.
Hip fractures were identified by computerized hospital discharge diagnoses.
Charlson comorbidity index was calculated based on additional diagnoses and
categorized (0, 1, and >=2). Summer was defined as June, July, and August and
winter as December, January, and February. Incidence rate ratios for hip fracture
according to season were calculated by negative binomial models. RESULTS: In
patients aged 50-103 years, 136,140 eligible fractures were identified (72.5 %
women). The relative risk of hip fracture in winter versus summer was 1.40 (95 %
confidence interval (CI) 1.36-1.45) in men and 1.26 (95 % CI 1.23-1.28) in women.
June had the lowest number of fractures in both genders. We found seasonal
variation in all subgroups by age and gender, although least pronounced in
patients >79 years. There was a significant interaction between season and
comorbidity (p = 0.022). When comparing winter to summer, we found relative risks
of 1.40 (95 % CI 1.31-1.50) in patients with Charlson index = 0, 1.29 (95 % CI
1.19-1.40) in patients with Charlson index = 1, and 1.18 (95 % CI 1.08-1.28) in
patients with Charlson index >=2. CONCLUSIONS: There was a distinct seasonal
variation in hip fracture incidence, present in all subgroups of gender, age, or
comorbidity. This variation should be accounted for when planning health-care
services.
PMID- 25134978
TI - Optimising beamformer regions of interest analysis.
AB - Beamforming is a spatial filtering based source reconstruction method for EEG and
MEG that allows the estimation of neuronal activity at a particular location
within the brain. The computation of the location specific filter depends solely
on an estimate of the data covariance matrix and on the forward model. Increasing
the number of M/EEG sensors, increases the quantity of data required for accurate
covariance matrix estimation. Often however we have a prior hypothesis about the
site of, or the signal of interest. Here we show how this prior specification, in
combination with optimal estimations of data dimensionality, can give enhanced
beamformer performance for relatively short data segments. Specifically we show
how temporal (Bayesian Principal Component Analysis) and spatial (lead field
projection) methods can be combined to produce improvements in source estimation
over and above employing the approaches individually.
PMID- 25134980
TI - Women's perspectives and experiences on screening for osteoporosis (Risk
stratified Osteoporosis Strategy Evaluation, ROSE).
AB - This study aimed to investigate women's perspectives and experiences with
screening for osteoporosis. Focus groups and individual interviews were
conducted. Three main themes emerged: knowledge about osteoporosis, psychological
aspects of screening, and moral duty. Generally, screening was accepted due to
life experiences, self-perceived risk, and the preventive nature of screening.
PURPOSE: The risk-stratified osteoporosis strategy evaluation (ROSE) study is a
randomized prospective population-based trial investigating the efficacy of a
screening program to prevent fractures in women aged 65-80 years. It is
recommended by the World Health Organization that a set of criteria are met
before a screening program is implemented. This sub-study aims to investigate
women's perspectives and experiences with the ROSE screening program in relation
to the patient-related criteria recommended by the World Health Organization.
METHODS: A qualitative study was carried out involving 31 women by way of 8 focus
group interviews and 11 individual interviews. Principles from critical
psychology guided the analysis. RESULTS: Women's perspectives and experiences
with the screening program were described by three main themes: knowledge about
osteoporosis, psychological aspects of screening, and moral duty. The women
viewed the program in the context of their everyday life and life trajectories.
Age, lifestyle, and knowledge about osteoporosis were important to how women
ascribed meaning to the program, how they viewed the possibilities and
limitations, and how they rationalized their actions and choices. The women
displayed limited knowledge about osteoporosis and its risk factors. However,
acceptance was based on prior experience, perceived risk, and evaluation of
preventive measures. To be reassured or concerned by screening was described as
important issues, as well as the responsibility for health-seeking behaviour.
CONCLUSION: In general, the women accepted the screening program. No major
ethical reservations or adverse psychological consequences were detected. Only a
minority of women declined screening participation due to a low perceived risk of
osteoporosis.
PMID- 25134981
TI - Transcatheter valve-in-valve implantation for degenerated mitral valve
bioprosthesis under 3D echocardiographic guidance.
AB - Transcatheter mitral valve-in-valve replacement is increasingly being performed
as operator and center experience in transcatheter valve replacement technology
and techniques have accrued. Complications, such as valve embolization and
paravalvular regurgitation, still occur and relate to valve deployment. The use
of novel imaging techniques, such as 3D echocardiography, allows for better
differentiation of cardiac structures and appropriate positioning of the
transcatheter valve using well-visualized anatomical landmarks. Here the authors
describe in images and video the use of 3D echocardiography for deployment of a
mitral valve-in-valve.
PMID- 25134982
TI - Pregnant couples at increased risk for common aneuploidies choose maximal
information from invasive genetic testing.
AB - Genomic array detects more pathogenic chromosome aberrations than conventional
karyotyping (CK), including genetic variants associated with a susceptibility for
neurodevelopmental disorders; susceptibility loci (SL). Consensus regarding the
scope of invasive prenatal diagnosis (PND) pregnant couples should be offered is
lacking. This study examined pregnant couples' preferences, doubts and
satisfaction regarding the scope of invasive PND. Eighty-two couples choosing
prenatal screening (PNS) and 59 couples choosing invasive PND were offered a
choice between 5 (comparable to CK) and 0.5 Mb resolution array analysis
outcomes, the latter with or without reporting SL. A pre-test self-report
questionnaire and post-test telephone interview assessed their choices in-depth.
Actual (PND) and hypothetical (PNS) choices differed significantly (p < 0.001).
Ninety-five percent of the couples in the PND group chose 0.5 Mb array, vs 69% in
the PNS group. Seven percent of the PND group wished not to be informed of SL.
Ninety percent was satisfied with their choice and wished to decide about the
scope themselves. Pregnant couples wish to make their own choices regarding the
scope of invasive PND. It therefore seems justified to offer them a choice in
both the resolution of array and disclosure of SL.
PMID- 25134983
TI - Cytotoxicity of purified listeriolysin O on mouse and human leukocytes and
leukaemia cells.
AB - BACKGROUND: Listeriolysin O (LLO) is the main virulence factor of Listeria
monocytogenes and facilitates the intracellular survival of the pathogen. Some of
its characteristics endorse the growing popularity of LLO for use in
biotechnology, particularly in the development of novel vaccines. Here, we
evaluate the use of LLO to eradicate leukaemia cells. RESULTS: A purified LLO
preparation was obtained by affinity chromatography. The LLO preparation
procedure was optimized and purified LLO was tested for optimal conditions of
storage including temperature, application of proteinase inhibitors and serum
components. We demonstrated the possibility of regulating LLO activity by
adjusting cell membrane cholesterol content. The LLO preparation had haemolytic
activity and had a cytotoxic effect on the human T-leukaemia Jurkat cell line as
well as mouse and human peripheral blood mononuclear cells. CONCLUSIONS: LLO has
a very potent cytotoxic activity towards human leukocytes. Importantly, the
cytotoxic activity was easily regulated in vitro and could be restricted to areas
containing malignant cells, raising the possibility of future clinical
application of LLO for leukaemia treatment.
PMID- 25134985
TI - A systematic review evaluating the impact of online or blended learning vs. face
to-face learning of clinical skills in undergraduate nurse education.
AB - AIM: To determine whether the use of an online or blended learning paradigm has
the potential to enhance the teaching of clinical skills in undergraduate
nursing. BACKGROUND: The need to adequately support and develop students in
clinical skills is now arguably more important than previously considered due to
reductions in practice opportunities. Online and blended teaching methods are
being developed to try and meet this requirement, but knowledge about their
effectiveness in teaching clinical skills is limited. DESIGN: Mixed methods
systematic review, which follows the Joanna Briggs Institute User guide version
5. DATA SOURCES: Computerized searches of five databases were undertaken for the
period 1995-August 2013. REVIEW METHODS: Critical appraisal and data extraction
were undertaken using Joanna Briggs Institute tools for
experimental/observational studies and interpretative and critical research. A
narrative synthesis was used to report results. RESULTS: Nineteen published
papers were identified. Seventeen papers reported on online approaches and only
two papers reported on a blended approach. The synthesis of findings focused on
the following four areas: performance/clinical skill, knowledge, self
efficacy/clinical confidence and user experience/satisfaction. The e-learning
interventions used varied throughout all the studies. CONCLUSION: The available
evidence suggests that online learning for teaching clinical skills is no less
effective than traditional means. Highlighted by this review is the lack of
available evidence on the implementation of a blended learning approach to
teaching clinical skills in undergraduate nurse education. Further research is
required to assess the effectiveness of this teaching methodology.
PMID- 25134986
TI - Hereditary angioedema with F12 mutation: factors modifying the clinical
phenotype.
AB - BACKGROUND: Hereditary angioedema (HAE) with normal C1 inhibitor (C1Inh)
associated with the c.983C>A and c.983C>G mutations of the F12 gene (FXII-HAE) is
a rare condition, and presents with highly variable clinical expression. On the
basis of data gathered from a large carrier cohort, we assessed the modifiers
affecting the clinical phenotype. METHODS: We analyzed clinical and biological
data recorded from 118 mutation carriers (80 symptomatic and 38 asymptomatic), 58
noncarrier relatives from 40 families, and 200 healthy donors. Disease severity
was scored in relation to frequency and location of edema, as well as age at
disease onset. To predict FXII-HAE disease severity, we analyzed the biological
phenotype [C1Inh, C4, spontaneous amidase, angiotensin-I-converting enzyme (ACE),
aminopeptidase P (APP), and carboxypeptidase N/M (CPN)] by means of logistic
regression (Akaike information criterion) and odds ratio (OR). RESULTS:
Meaningful variables contributed to FXII-HAE, with the kinin catabolism enzymes
ACE and CPN exhibiting a significant inverse relationship with disease severity
(OR = 0.36, 95% CI 0.23-0.59, P < 0.001; OR = 0.58, 95% CI 0.36-0.91, P < 0.05,
respectively). CPN activities were 37.5 (28.5-41.3) nmol/ml/min and 38.5 (32.8
45.6) for FXII-HAE asymptomatic and symptomatic carriers, respectively, and 37.9
(30.5-43.7) nmol/ml/min for noncarriers. Angiotensin-I-converting enzyme
activities were 58 (44-76) and 49 (35-59) nmol/ml/min for FXII-HAE asymptomatic
and symptomatic carriers, respectively, and 56 (49-66) nmol/ml/min for
noncarriers. CONCLUSIONS: The FXII-HAE is associated with modifiers, for example
kinin catabolism enzymes, ACE and CPN, different from those recognized in HAE
with C1Inh deficiency.
PMID- 25134987
TI - The deubiquitinating enzyme CYLD controls apical docking of basal bodies in
ciliated epithelial cells.
AB - CYLD is a tumour suppressor gene mutated in familial cylindromatosis, a genetic
disorder leading to the development of skin appendage tumours. It encodes a
deubiquitinating enzyme that removes Lys63- or linear-linked ubiquitin chains.
CYLD was shown to regulate cell proliferation, cell survival and inflammatory
responses, through various signalling pathways. Here we show that CYLD localizes
at centrosomes and basal bodies via interaction with the centrosomal protein
CAP350 and demonstrate that CYLD must be both at the centrosome and catalytically
active to promote ciliogenesis independently of NF-kappaB. In transgenic mice
engineered to mimic the smallest truncation found in cylindromatosis patients,
CYLD interaction with CAP350 is lost disrupting CYLD centrosome localization,
which results in cilia formation defects due to impairment of basal body
migration and docking. These results point to an undiscovered regulation of
ciliogenesis by Lys63 ubiquitination and provide new perspectives regarding CYLD
function that should be considered in the context of cylindromatosis.
PMID- 25134988
TI - Should electric fans be used during a heat wave?
AB - Heat waves continue to claim lives, with the elderly and poor at greatest risk. A
simple and cost-effective intervention is an electric fan, but public health
agencies warn against their use despite no evidence refuting their efficacy in
heat waves. A conceptual human heat balance model can be used to estimate the
evaporative requirement for heat balance, the potential for evaporative heat loss
from the skin, and the predicted sweat rate, with and without an electrical fan
during heat wave conditions. Using criteria defined by the literature, it is
clear that fans increase the predicted critical environmental limits for both the
physiological compensation of endogenous/exogenous heat, and the onset of
cardiovascular strain by an air temperature of ~3-4 degrees C, irrespective of
relative humidity (RH) for the young and elderly. Even above these critical
limits, fans would apparently still provide marginal benefits at air temperatures
as high as 51.1 degrees C at 10%RH for young adults and 48.1 degrees C at 10%RH
for the elderly. Previous concerns that dehydration would be exacerbated with fan
use do not seem likely, except under very hot (>40 degrees C) and dry (<10%RH)
conditions, when predicted sweat losses are only greater with fans by a minor
amount (~20-30 mL/h). Relative to the peak outdoor environmental conditions
reported during ten of the most severe heat waves in recent history, fan use
would be advisable in all of these situations, even when reducing the predicted
maximum sweat output for the elderly. The protective benefit of fans appears to
be underestimated by current guidelines.
PMID- 25134990
TI - Efficient ammonium uptake and mobilization of vacuolar arginine by Saccharomyces
cerevisiae wine strains during wine fermentation.
AB - BACKGROUND: Under N-limiting conditions, Saccharomyces cerevisiae strains display
a substantial variability in their biomass yield from consumed nitrogen -in
particular wine yeasts exhibit high growth abilities- that is correlated with
their capacity to complete alcoholic fermentation, a trait of interest for
fermented beverages industries. The aim of the present work was to assess the
contribution of nitrogen availability to the strain-specific differences in the
ability to efficiently use N-resource for growth and to identify the underlying
mechanisms. We compared the profiles of assimilation of several nitrogen sources
(mostly ammonium, glutamine, and arginine) for high and low biomass-producing
strains in various conditions of nitrogen availability. We also analyzed the
intracellular fate of nitrogen compounds. RESULTS: Strains clustered into two
groups at initial nitrogen concentrations between 85 and 385 mg N.L(-1): high
biomass producers that included wine strains, were able to complete fermentation
of 240 g.L(-1) glucose and quickly consume nitrogen, in contrast to low biomass
producers. The two classes of strains exhibited distinctive characteristics that
contributed to their differential capacity to produce biomass. The contribution
of each characteristic varied according to nitrogen availability. In high biomass
producers, the high rate of ammonium uptake resulted in an important consumption
of this preferred nitrogen source that promoted the growth of these yeasts when
nitrogen was provided in excess. Both classes of yeast accumulated poor nitrogen
sources, mostly arginine, in vacuoles during the first stages of growth. However,
at end of the growth phase when nitrogen had become limiting, high biomass
producers more efficiently used this vacuolar nitrogen fraction for protein
synthesis and further biomass formation than low biomass producers. CONCLUSIONS:
Overall, we demonstrate that the efficient management of the nitrogen resource,
including efficient ammonium uptake and efficient use of the amino acids stored
in vacuoles during the late stages of growth, might lead to high biomass
production by wine yeasts.
PMID- 25134991
TI - Reduced intraocular pressure after cataract surgery in patients with narrow
angles and chronic angle-closure glaucoma.
AB - PURPOSE: To evaluate the effect of cataract surgery on intraocular pressure (IOP)
in patients with narrow angles and chronic angle-closure glaucoma (ACG) and to
determine whether the change in IOP was correlated with the preoperative
pressure, axial length (AL), and anterior chamber depth (ACD). SETTING: Private
practice, Atlanta, Georgia, USA. DESIGN: Retrospective case series. METHODS:
Charts of patients with narrow angles or chronic ACG who had cataract surgery
were reviewed. All eyes had previous laser iridotomies. Data recorded included
preoperative and postoperative IOP, AL, and ACD. The preoperative IOP was used to
stratify eyes into 4 groups. RESULTS: The charts of 56 patients (83 eyes) were
reviewed. The mean reduction IOP in all eyes was 3.28 mm Hg (18%), with 88%
having a decrease in IOP. There was a significant correlation between
preoperative IOP and the magnitude of IOP reduction (r = 0.68, P < .001). The
mean decrease in IOP was 5.3 mm Hg in eyes with a preoperative IOP above 20 mm
Hg, 4.6 mm Hg in the over 18 to 20 mm Hg group, 2.5 mm Hg in the over 15 to 18 mm
Hg group, and 1.4 mm Hg in the 15 mm Hg or less group. The mean follow-up was 3.0
years +/- 2.3 (SD). CONCLUSIONS: Cataract surgery reduced IOP in patients with
narrow angles and chronic ACG. The magnitude of reduction was highly correlated
with preoperative IOP and weakly correlated with ACD. FINANCIAL DISCLOSURE: No
author has a financial or proprietary interest in any material or method
mentioned.
PMID- 25134989
TI - Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4
mediated inflammatory monocyte migration.
AB - Inflammatory monocytes play an important role in host defense against infections.
However, the regulatory mechanisms of transmigration into infected tissue are not
yet completely understood. Here we show that mice deficient in MAIR-II (also
called CLM-4 or LMIR2) are more susceptible to caecal ligation and puncture (CLP)
induced peritonitis than wild-type (WT) mice. Adoptive transfer of inflammatory
monocytes from WT mice, but not from MAIR-II, TLR4 or MyD88-deficient mice,
significantly improves survival of MAIR-II-deficient mice after CLP. Migration of
inflammatory monocytes into the peritoneal cavity after CLP, which is dependent
on VLA-4, is impaired in above mutant and FcRgamma chain-deficient mice.
Lipopolysaccharide stimulation induces association of MAIR-II with FcRgamma chain
and Syk, leading to enhancement of VLA-4-mediated adhesion to VCAM-1. These
results indicate that activation of MAIR-II/FcRgamma chain by TLR4/MyD88-mediated
signalling is essential for the transmigration of inflammatory monocytes from the
blood to sites of infection mediated by VLA-4.
PMID- 25134992
TI - Comparison of the metal-to-ceramic bond strengths of four noble alloys with press
on-metal and conventional porcelain layering techniques.
AB - STATEMENT OF PROBLEM: New noble alloys for metal ceramic restorations introduced
by manufacturers are generally lower-cost alternatives to traditional higher-gold
alloys. Information about the metal-to-ceramic bond strength for these alloys,
which is needed for rational clinical selection, is often lacking. PURPOSE: The
purpose of this study was to evaluate the bond strength of 4 recently introduced
noble alloys by using 2 techniques for porcelain application. MATERIAL AND
METHODS: Aquarius Hard (high-gold: 86.1 gold, 8.5 platinum, 2.6 palladium, 1.4
indium; values in wt. %), Evolution Lite (reduced-gold: 40.3 gold, 39.3
palladium, 9.3 indium, 9.2 silver, 1.8 gallium), Callisto 75 Pd (palladium-silver
containing gold: 75.2 palladium, 7.1 silver, 2.5 gold, 9.3 tin, 1.0 indium), and
Aries, (conventional palladium-silver: 63.7 palladium, 26.0 silver, 7.0 tin, 1.8
gallium, 1.5 indium) were selected for bonding to leucite-containing veneering
porcelains. Ten metal ceramic specimens that met dimensional requirements for
International Organization for Standardization (ISO) Standard 9693 were prepared
for each alloy by using conventional porcelain layering and press-on-metal
methods. The 3-point bending test in ISO Standard 9693 was used to determine bond
strength. Values were compared with 2-way ANOVA (maximum likelihood analysis, SAS
Mixed Procedure) and the Tukey test (alpha=.05). RESULTS: Means (standard
deviations) for bond strength with conventional porcelain layering were as
follows: Aquarius Hard (50.7 +/-5.5 MPa), Evolution Lite (40.2 +/-3.3 MPa),
Callisto 75 Pd (37.2 +/-3.9 MPa), and Aries (34.0 +/-4.9 MPa). For the press-on
metal technique, bond strength results were as follows: Aquarius Hard (33.7 +/
11.5 MPa), Evolution Lite (34.9 +/-4.5 MPa), Callisto 75 Pd (37.2 +/-11.9 MPa),
and Aries (30.7 +/-10.8 MPa). From statistical analyses, the following 3
significant differences were found for metal-to-ceramic bond strength: the bond
strength for Aquarius Hard was significantly higher for conventional porcelain
layers compared with the press-on-metal technique; the bond strength for Aquarius
Hard with conventional porcelain layers was significantly higher than the bond
strengths for the other 3 alloys with conventional porcelain layers; and the bond
strength for Aquarius Hard with conventional porcelain layers was significantly
higher than the bond strength for Callisto 75 Pd with conventional porcelain
layers and the other 3 alloys with the press-on-metal technique. CONCLUSIONS: For
both conventional layering and press-on-metal techniques, all 4 noble alloys had
a mean metal-to-ceramic bond strength that substantially exceeded the 25 MPa
minimum in the ISO Standard 9693. The results for Aries support the
manufacturer's recommendation not to use the press-on-metal technique for alloys
that contain more than 10% silver.
PMID- 25134993
TI - Evaluating the ability of dental technician students and graduate dentists to
match tooth color.
AB - STATEMENT OF PROBLEM: The ability of dental technician students to match tooth
shade with the Vita 3D-Master shade guide and Toothguide Training Box has not
been investigated. PURPOSE: The purpose of this study was to evaluate and compare
the shade-matching ability of dental technician students and graduate dentists
using the Vita 3D-Master shade guide. MATERIAL AND METHODS: Twenty-nine dental
technician students (DTS group) and 30 graduate dentists (GD group) participated
in this study. The Toothguide Training Box (TTB) was used to train the
participants and test their shade-matching abilities. Shade-matching ability was
evaluated with 3 exercises and a final test, all of which are components of the
TTB. The number of mistakes for each participant for value (L), chroma (c), and
hue (h) were recorded during the exercises and the final test, and the mistake
ratios were calculated. Color difference (DeltaE) values for each shade were
calculated from the L*, a*, and b* values of the Vita 3D-Master shade guide for
each participant in both groups. The Mann-Whitney U test was used to determine
statistically significant differences between the L, c, and h mistake ratios of
the 2 groups, and the Student t test was used to determine statistically
significant differences between the final test scores and the DeltaE values of
the groups (alpha=.05). RESULTS: The mistake ratio for L in the GD group was
significantly higher than that of the DTS group (P<.05), whereas the mistake
ratio for h in the DTS group was higher (P<.001). No significant differences were
observed between the groups regarding the mistake ratios for c (P>.05). With
regard to the final test scores and the DeltaE values, no significant differences
were found between the groups (P<.001), and the DTS group received higher scores
than the GD group (912 and 851). The mean DeltaE values for the DTS and GD groups
were 1.72 and 2.92. CONCLUSIONS: DTSs made more mistakes in the h parameter than
GDs, and GDs made more mistakes in the L parameter than DTSs. With regard to the
final test scores and the DeltaE values, DTSs were more successful in shade
matching than GDs.
PMID- 25134994
TI - Evaluation of an optimized shade guide made from porcelain powder mixtures.
AB - STATEMENT OF PROBLEM: Color errors associated with current shade guides and
problems with color selection and duplication are still challenging for
restorative dentists. PURPOSE: The purpose of this study was to evaluate an
optimized shade guide for visual shade duplication. MATERIAL AND METHODS: Color
distributions (L*, a*, and b*) of the maxillary left central incisors of 236
participants, whose ages ranged from 20 to 60, were measured with a
spectrophotometer. Based on this color map, an optimized shade guide was designed
with 14 shade tabs evenly distributed within the given color range of the natural
incisors. The shade tabs were fabricated with porcelain powder mixtures and
conventional laboratory procedures. A comparison of shade duplication by using
the optimized and Vitapan Classical shade guides was conducted. Thirty Chinese
participants were involved, and the colors of the left maxillary incisors were
selected by using 2 shade guides. Metal ceramic crowns were fabricated according
to the results of the shade selection. The colors of the shade tabs, natural
teeth, and the ceramic crowns were measured with a spectrophotometer. The color
differences among the natural teeth, the shade tabs, and the corresponding metal
ceramic crowns were calculated and analyzed (alpha=.017). RESULTS: Significant
differences were found in both phases of shade determination and shade
duplication (P<.017). The total number of color errors with the optimized shade
guide was 3.5, which was significantly less than that of Vitapan, 5.1 (P<.001).
CONCLUSIONS: The optimized shade guide system improved performance not only in
the color selection phase but also in the color of the fabricated crowns.
PMID- 25134995
TI - Scanning accuracy and precision in 4 intraoral scanners: an in vitro comparison
based on 3-dimensional analysis.
AB - STATEMENT OF PROBLEM: Intraoral scanners may use proprietary acquisition and
manufacturing processes. However, limited information is available regarding
their accuracy, their precision, and the influence that refraction or coating may
have on their output. PURPOSE: The purpose of the study was to evaluate the
scanning accuracy and precision of 4 intraoral scanners and to assess the
influence of different test materials and coating thicknesses. MATERIAL AND
METHODS: Models were fabricated in 3 materials (polymethyl methacrylate [Telio
CAD], titanium, and zirconia) and reference scanned with an industrial optical
scanner. The models were scanned with intraoral scanners (3M Lava COS, Cerec
AC/Bluecam, E4D, and iTero). A thick layer of coating was applied and scanned (3M
Lava COS). Further evaluation on a gypsum cast was undertaken for the E4D system.
Data were evaluated by using 3-dimensional analysis with "3D compare" software
commands (3D compare analysis) regarding standard, mean, and maximum deviations,
with subsequent statistical analysis. RESULTS: The 3M Lava COS, Cerec AC/Bluecam,
and iTero generally displayed similar results regarding deviations. Maximum
deviations, however, increased by several factors for the noncoating scanners
(iTero and E4D). Statistical significance was found regarding material properties
for noncoating scanners (P<.05). iTero displayed consistent material-specific,
localized errors on the translucent material (Telio CAD). E4D showed the largest
deviations. Scans of the gypsum cast displayed specific localized areas with
greater deviations. Excessive coating was nonsignificant. CONCLUSIONS:
Significant differences were found between the coating and noncoating scanners,
and specific scanning errors for the system with parallel confocal microscopy
were found for certain model materials. Specific areas of sizable deviations for
the system with laser triangulation technology can be explained by the scanner
design and noncoating technology. Excessive coating had no negative effect.
PMID- 25134996
TI - Effect of gypsum separating media on the appearance of stone cast surfaces.
AB - STATEMENT OF PROBLEM: Several well-known parameters influence the appearance of
the denture base surface, including proper isolation of the dental stone. There
is lack of data describing the influence of this parameter on the appearance of
the denture base surface. PURPOSE: The purpose of this study was to evaluate the
effectiveness of 2 dental stone separating media on the surface of the denture
base. MATERIAL AND METHODS: A conventional flasking technique for fabricating a
denture base was used. Twenty casts were poured with Type III yellow dental stone
to produce 20 identical denture bases. Each cast was sectioned into halves. One
half of the cast was treated with Al-Cote (control group) and the other half with
Iso-K separating material. Once the denture base was finished, a single examiner,
blinded to the experiment, visually compared the 2 surfaces of each cast (right
and left part of the cast) under natural light to determine which surface was
glossier. The McNemar test (.05 significance level) was used to compare the
discordant pairs (20 discordant pairs). RESULTS: Two pairs (10%) were glossier
than the Iso-K treatment, and 18 pairs (90%) within the Iso-K treatment were
glossier than the treatment with Al-Cote. A statistically significant difference
was found between the 2 treatments (P<.001). The odds ratio was 9.00, with a 95%
confidence interval of 2.155 to 79.981. CONCLUSIONS: When used according to the
manufacturer's instructions, denture surfaces treated with Iso-K appeared
glossier than when treated with Al-Cote separating material.
PMID- 25134997
TI - A technique to evaluate custom tray border extensions before peripheral molding.
PMID- 25134998
TI - Methylated ZNF582 gene as a marker for triage of women with Pap smear reporting
low-grade squamous intraepithelial lesions - a Taiwanese Gynecologic Oncology
Group (TGOG) study.
AB - OBJECTIVE: Our previous work revealed that host genes ZNF582, PTPRR, PAX1, and
SOX1 are highly methylated in cervical intraepithelial neoplasias grade 3 or
worse (CIN3(+)). In this study, we used a standardized testing assay to evaluate
the clinical efficacy of these biomarkers in the triage of cytological diagnoses
of low-grade squamous intraepithelial lesions (LSILs), and compared the
performance with human papillomavirus (HPV) testing. METHODS: This 2-year
multicenter prospective study examined a population of 230 women from 12 medical
centers who were diagnosed with LSILs on cervical cytology. Cervical scrapings
were obtained prior to a colposcopy-directed biopsy for quantitative methylation
analysis of ZNF582, PTPRR, PAX1, and SOX1, and HPV testing. Using logistic
regression and receiver operating characteristic curve analyses, the abilities of
methylated genes and HPV to predict CIN3(+) were assessed. RESULTS: Fifteen
(6.5%) of the 230 women with a cytological diagnosis of LSIL were confirmed to
have CIN3(+) after a colposcopy-directed biopsy. Among the 4 methylated genes,
ZNF582 was found to be the best biomarker for detecting CIN3(+). The
sensitivities for methylated ZNF582 and HPV testing were 73% and 80%, and the
specificities were 71% and 28%, respectively. The odds ratio for predicting
CIN3(+) using methylated ZNF582 was 6.8 (95% confidence interval (CI) 2.1-22.1),
which was much better than HPV testing (OR=1.6, 95% CI 0.4-5.8). CONCLUSION: This
is the first study to show that ZNF582 methylation analysis of cervical swabs may
be a promising choice in the positive triage of cytological diagnoses of LSILs.
PMID- 25135000
TI - Role of toll-like receptors in cervical, endometrial and ovarian cancers: a
review.
AB - OBJECTIVE: The Toll-like receptors (TLRs) have been implicated in inflammation,
innate immunity and cancer. The goal of this paper is to review the available
published research about Toll-like receptors and their roles in gynecologic
malignancies. METHODS: A Medline search was conducted and published articles from
the late 1990s to the present (2014) were reviewed using search phrases, Toll
like receptors and cervical, endometrial and ovarian cancers. RESULTS: TLR4 and
TLR5 are commonly absent in normal cervix, however TLR5 expression is strong in
high grade cervical dysplasia as well as invasive cancer. The expression of TLR3
and TLR4 is low in endometrial cancer. TLR2, TLR3, TLR4 and TLR5 are highly
expressed in normal and neoplastic ovarian epithelium. TLR3 has been shown to
have a dual function: it can contribute to tumor elimination by upregulation of
interferons alpha and beta (INF) and natural killer cell (NK) activation or it
can indirectly contribute to tumor progression. CONCLUSIONS: Inflammation is an
essential element in tumorigenesis. Toll-like receptors can trigger an
inflammatory response and cell survival in the tumor micro-environment. TLRs are
critical immunomodulators that may play an important role in the development of
gynecologic cancers. Currently TLR agonists are being investigated for a
potential role as an adjuvant in the treatment of gynecologic malignancies.
PMID- 25135001
TI - Needs assessment of palliative care education in gynecologic oncology fellowship:
we're not teaching what we think is most important.
AB - OBJECTIVES: We sought to characterize gynecologic oncology fellowship directors'
perspectives on (1) inclusion of palliative care (PC) topics in current
fellowship curricula, (2) relative importance of PC topics and (3) interest in
new PC curricular materials. METHODS: An electronic survey was distributed to
fellowship directors, assessing current teaching of 16 PC topics meeting
ABOG/ASCO objectives, relative importance of PC topics and interest in new PC
curricular materials. Descriptive and correlative statistics were used. RESULTS:
Response rate was 63% (29/46). 100% of programs had coverage of some PC topic in
didactics in the past year and 48% (14/29) have either a required or elective PC
rotation. Only 14% (4/29) have a written PC curriculum. Rates of explicit
teaching of PC topics ranged from 36% (fatigue) to 93% (nausea). Four of the top
five most important PC topics for fellowship education were communication topics.
There was no correlation between topics most frequently taught and those
considered most important (rs=0.11, p=0.69). All fellowship directors would
consider using new PC curricular materials. Educational modalities of greatest
interest include example teaching cases and PowerPoint slides. CONCLUSIONS:
Gynecologic oncology fellowship directors prioritize communication topics as the
most important PC topics for fellows to learn. There is no correlation between
which PC topics are currently being taught and which are considered most
important. Interest in new PC curricular materials is high, representing an
opportunity for curricular development and dissemination. Future efforts should
address identification of optimal methods for teaching communication to
gynecologic oncology fellows.
PMID- 25134999
TI - Oxysterols synergize with statins by inhibiting SREBP-2 in ovarian cancer cells.
AB - OBJECTIVE: Determine mechanisms responsible for enhanced statin efficacy in a
novel statin combination we name STOX (STatin-OXysterol). METHODS: Ovarian cancer
cell lines were treated with combinations of statins and oxysterols. Cell
viability was determined by a modified MTT assay. Apoptosis was evaluated by
immunoblotting of PARP and DAPI-mediated visualization of apoptotic nuclei. STOX
effects on the expression of genes of the mevalonate pathway were assessed by
real-time qPCR and immunoblotting. siRNA-mediated gene silencing was used to test
the involvement of oxysterol-mediated repression of SREBP-2 in STOX synergy. The
impact of statin-mediated inhibition of protein prenylation and on cholesterol
homeostasis was evaluated. RESULTS: Oxysterols dramatically enhance cytotoxicity
of statins in ovarian cancer cells through increased apoptosis. Decreased
expression of SREBP-2 down-regulates the mevalonate pathway and prevents the
active statin-induced sterol feedback, enhancing statin toxicity. Comparison of
two ovarian cancer cell lines reveals two distinct mechanisms of statin induced
toxicity, namely, dependence on protein geranylgeranylation and/or perturbation
of cellular cholesterol levels. CONCLUSIONS: We provide evidence of statins'
mechanisms of cytotoxicity in different ovarian cancer cells and discovered a new
approach to significantly enhance the anti-tumor activity of statins. These
observations provide a potential new path to improve statins as a treatment
against ovarian cancer with obtainable dosages.
PMID- 25135002
TI - Factors affecting diagnosis and management of hypertension in Mazowe District of
Mashonaland Central Province in Zimbabwe: 2012.
AB - BACKGROUND: From 2005 to 2011 Mazowe District recorded a gradual decline in
prevalence of hypertension in the face of rising incidence of complications like
stroke. This raised questions on whether diagnosis and management of hypertensive
patients is being done properly. METHODS: We conducted an analytic cross
sectional study at three hospitals in Mazowe District where we randomly selected
201 of 222 patients from out patients departments and interviewed a convenience
sample of 23 healthcare workers. Structured interviewer administered
questionnaires were used to collect data on demographic characteristics and
knowledge from patients, as well as knowledge and practices from health workers.
Physical measurements were done on all patients. Frequencies; proportions, odds
ratios, Chi square test and stratified & logistic regression analysis were done
using Epi info version 3.5.4 while graphs were generated using Microsoft
excel(r). Calculations were done at 95% confidence interval. RESULTS: Prevalence,
awareness, control, compliance, and complication rate of hypertension were:
69.7%, 56.2%, 22.0%, 59.8% and 20.7% respectively. Independent risk factors for
hypertension were age (POR 3.09; 95% CI: 1.27-7.5), obesity (POR 4.37; 95% CI:
1.83-10.4), and previous high blood pressure reading (POR 19.86; 95% CI: 8.61
45.8). Complications included cardiac failure (8.6%), visual defects (4.3%) and
stroke (3.6%). Co-morbid human immunodeficiency virus (10.7%) and diabetes
mellitus (12.1%) were identified among respondents. Knowledge was poor in 47.7%
of health workers. CONCLUSIONS: Risk factors found in this study are consistent
with other studies. Health service factors are the main reasons for poor
diagnosis and management of hypertension. Health workers need training on
diagnosis and management of hypertension. Guidelines, digital sphygmomanometers
and adequate drug supply are needed. District has since purchased digital BP
machines and requested assistance with training on clinical features of
hypertension, use of digital machines, and how to properly measure BP. A policy
document on non-communicable diseases including hypertension was subsequently
developed by the Ministry of Health and Child Care and currently awaiting
endorsement by parliament.
PMID- 25135003
TI - Facilitation of corticospinal excitability by virtual reality exercise following
anodal transcranial direct current stimulation in healthy volunteers and subacute
stroke subjects.
AB - BACKGROUND: There is growing evidence that the combination of non-invasive brain
stimulation and motor skill training is an effective new treatment option in
neurorehabilitation. We investigated the beneficial effects of the application of
transcranial direct current stimulation (tDCS) combined with virtual reality (VR)
motor training. METHODS: In total, 15 healthy, right-handed volunteers and 15
patients with stroke in the subacute stage participated. Four different
conditions (A: active wrist exercise, B: VR wrist exercise, C: VR wrist exercise
following anodal tDCS (1 mV, 20 min) on the left (healthy volunteer) or affected
(stroke patient) primary motor cortex, and D: anodal tDCS without exercise) were
provided in random order on separate days. We compared during and post-exercise
corticospinal excitability under different conditions in healthy volunteers (A,
B, C, D) and stroke patients (B, C, D) by measuring the changes in amplitudes of
motor evoked potentials in the extensor carpi radialis muscle, elicited with
single-pulse transcranial magnetic stimulation. For statistical analyses, a
linear mixed model for a repeated-measures covariance pattern model with
unstructured covariance within groups (healthy or stroke groups) was used.
RESULTS: The VR wrist exercise (B) facilitated post-exercise corticospinal
excitability more than the active wrist exercise (A) or anodal tDCS without
exercise (D) in healthy volunteers. Moreover, the post-exercise corticospinal
facilitation after tDCS and VR exercise (C) was greater and was sustained for 20
min after exercise versus the other conditions in healthy volunteers (A, B, D)
and in subacute stroke patients (B, D). CONCLUSIONS: The combined effect of VR
motor training following tDCS was synergistic and short-term corticospinal
facilitation was superior to the application of VR training, active motor
training, or tDCS without exercise condition. These results support the concept
of combining brain stimulation with VR motor training to promote recovery after a
stroke.
PMID- 25135004
TI - Steady-state sulfur critical loads and exceedances for protection of aquatic
ecosystems in the U.S. Southern Appalachian Mountains.
AB - Atmospherically deposited sulfur (S) causes stream water acidification throughout
the eastern U.S. Southern Appalachian Mountain (SAM) region. Acidification has
been linked with reduced fitness and richness of aquatic species and changes to
benthic communities. Maintaining acid-base chemistry that supports native biota
depends largely on balancing acidic deposition with the natural resupply of base
cations. Stream water acid neutralizing capacity (ANC) is maintained by base
cations that mostly originate from weathering of surrounding lithologies. When
ambient atmospheric S deposition exceeds the critical load (CL) an ecosystem can
tolerate, stream water chemistry may become lethal to biota. This work links
statistical predictions of ANC and base cation weathering for streams and
watersheds of the SAM region with a steady-state model to estimate CLs and
exceedances. Results showed that 20.1% of the total length of study region
streams displayed ANC <100 MUeq?L(-1), a level at which effects to biota may be
anticipated; most were 4th or lower order streams. Nearly one-third of the stream
length within the study region exhibited CLs of S deposition <50 meq?m(-2)?yr(
1), which is less than the regional average S deposition of 60 meq?m(-2)?yr(-1).
Owing to their geologic substrates, relatively high elevation, and cool and moist
forested conditions, the percentage of stream length in exceedance was highest
for mountain wilderness areas and in national parks, and lowest for privately
owned valley bottom land. Exceedance results were summarized by 12-digit
hydrologic unit code (subwatershed) for use in developing management goals and
policy objectives, and for long-term monitoring.
PMID- 25135005
TI - Consumer willingness to invest money and time for benefits of lifestyle behaviour
change: an application of the contingent valuation method.
AB - OBJECTIVE: To use contingent valuation (CV) to derive individual consumer values
for both health and broader benefits of a public-health intervention directed at
lifestyle behaviour change (LBC) and to examine the feasibility and validity of
the method. METHOD: Participants of a lifestyle intervention trial (n = 515) were
invited to complete an online CV survey. Respondents (n = 312) expressed
willingness to invest money and time for changes in life expectancy, health
related quality of life (HRQOL) and broader quality of life aspects. Internal
validity was tested for by exploring associations between explanatory variables
(i.e. income, paid work, experience and risk factors for cardiovascular diseases)
and willingness to invest, and by examining ordering effects and respondents'
sensitivity to the scope of the benefits. RESULTS: The majority of respondents
(94.3%) attached value to benefits of LBC, and 87.4% were willing to invest both
money and time. Respondents were willing to invest more for improvements in HRQOL
(?42/month; 3 h/week) and broader quality of life aspects (?40/month; 2.6 h/week)
than for improvements in life expectancy (?24/month; 2 h/week). Protest answers
were limited (3%) and findings regarding internal validity were mixed.
CONCLUSION: The importance of broader quality of life outcomes to consumers
suggests that these outcomes are relevant to be considered in the decision
making. Our research showed that CV is a feasible method to value both health and
broader outcomes of LBC, but generalizability to other areas of public health
still needs to be examined. Mixed evidence regarding internal validity pleads for
caution to use CV as only the base for decision making.
PMID- 25135006
TI - What level of bowel prep quality requires early repeat colonoscopy: systematic
review and meta-analysis of the impact of preparation quality on adenoma
detection rate.
AB - OBJECTIVES: Current guidelines recommend early repeat colonoscopy when bowel
preparation quality is inadequate, defined as inability to detect polyps >5 mm,
but no data link specific bowel preparation categories or scores to this
definition. Nevertheless, most physicians use a shortened screening/surveillance
interval in patients with intermediate-quality preparation. We determined whether
different levels of bowel preparation quality are associated with differences in
adenoma detection rates (ADRs: proportion of colonoscopies with >=1 adenoma) to
help guide decisions regarding early repeat colonoscopy-with primary focus on
intermediate-quality preparation. METHODS: MEDLINE and Embase were searched for
studies with adenoma or polyp detection rate stratified by bowel preparation
quality. Preparation quality definitions were standardized on the basis of
Aronchick definitions (excellent/good/fair/poor/insufficient), and primary
analyses of ADR trichotomized bowel preparation quality: high quality
(excellent/good), intermediate quality (fair), and low quality
(poor/insufficient). Dichotomized analyses of adequate (excellent/good/fair) vs.
inadequate (poor/insufficient) were also performed. RESULTS: Eleven studies met
the inclusion criteria. The primary analysis, ADR with intermediate- vs. high
quality preparation, showed an odds ratio (OR) of 0.94 (0.80-1.10) and absolute
risk difference of -1% (-3%, 2%). ADRs were significantly higher with both
intermediate-quality and high-quality preparation vs. low-quality preparation:
OR=1.39 (1.08-1.79) and 1.41 (1.21-1.64), with absolute risk increases of 5% for
both. ADR and advanced ADR were significantly higher with adequate vs. inadequate
preparation: OR=1.30 (1.19-1.42) and 1.30 (1.02-1.67). Studies did not report
other relevant outcomes such as total adenomas per colonoscopy. CONCLUSIONS: ADR
is not significantly different with intermediate-quality vs. high-quality bowel
preparation. Our results confirm the need for early repeat colonoscopy with low
quality bowel preparation, but suggest that patients with intermediate/fair
preparation quality may be followed up at standard guideline-recommended
surveillance intervals without significantly affecting quality as measured by
ADR.
PMID- 25135007
TI - Miralax with gatorade for bowel preparation: a meta-analysis of randomized
controlled trials.
AB - OBJECTIVES: Polyethylene glycol (PEG) is a very popular bowel preparation for
colonoscopy. However, its large volume may reduce patient compliance, resulting
in suboptimal preparation. Recently, a combination of Miralax and Gatorade has
been studied in various randomized controlled trials (RCTs) as a lower volume and
more palatable bowel preparation. However, results have varied. Therefore, we
conducted a meta-analysis assessing the use of Miralax-Gatorade (M-G) vs. PEG for
bowel preparation before colonoscopy. METHODS: Multiple databases were searched
(January 2014). RCTs on adults comparing M-G (238-255 g in 1.9 l that is 64 fl
oz) vs. PEG (3.8-4 l) for bowel preparation before colonoscopy were included. The
effects were analyzed by calculating pooled estimates of quality of bowel
preparation (satisfactory, unsatisfactory, excellent), patient tolerance (nausea,
cramping, bloating), and polyp detection by using odds ratio (OR) with fixed- and
random-effects models. RESULTS: Five studies met inclusion criteria (N=1,418),
with mean age ranging from 53.8 to 61.3 years. M-G demonstrated statistically
significantly fewer satisfactory bowel preparations as compared with PEG (OR
0.65; 95% confidence interval (CI): 0.43-0.98, P=0.04) but more willingness to
repeat preparation (OR 7.32; 95% CI: 4.88-10.98, P<0.01). Furthermore, no
statistically significant differences in polyp detection (P=0.65) or side effects
were apparent between the two preparations for nausea (P=0.71), cramping
(P=0.84), or bloating (P=0.50). Subgroup analysis revealed similar results for
split-dose M-G vs. split-dose PEG. CONCLUSIONS: M-G for bowel preparation before
colonoscopy was inferior to PEG in bowel preparation quality while demonstrating
no significant improvements in adverse effects or polyp detection. Therefore, PEG
appears superior to M-G for bowel preparation before colonoscopy.
PMID- 25135008
TI - ACG clinical guideline: the diagnosis and management of focal liver lesions.
AB - Focal liver lesions (FLL) have been a common reason for consultation faced by
gastroenterologists and hepatologists. The increasing and widespread use of
imaging studies has led to an increase in detection of incidental FLL. It is
important to consider not only malignant liver lesions, but also benign solid and
cystic liver lesions such as hemangioma, focal nodular hyperplasia,
hepatocellular adenoma, and hepatic cysts, in the differential diagnosis. In this
ACG practice guideline, the authors provide an evidence-based approach to the
diagnosis and management of FLL.
PMID- 25135009
TI - Characterization of type III TGF-beta receptor expression in invasive breast
carcinomas: a potential new marker and target for triple negative breast cancer.
AB - Invasive breast carcinomas are heterogeneous and exhibit distinct molecular
features and biological behavior. Understanding the underlying molecular events
that promote breast cancer progression is necessary to improve treatment and
prognostication. TGF-beta receptor III (TBR3) is a member of the TGF-beta
signaling pathway, with functions in cell proliferation and migration in
malignancies, including breast cancer. Recent studies propose that TBR3 may
function as a tumor suppressor and that its loss may correlate with disease
progression. However, there are limited data on the expression of TBR3 in breast
cancer in relationship to tumor type, hormonal receptor status and HER-2/neu, and
patient outcome. In this study, we investigated the expression of TBR3 in a
cohort of 205 primary invasive breast carcinomas in tissue microarrays (TMAs),
with comprehensive clinical, pathological and follow- up information. Sections
were stained for TBR3 and evaluated for intensity of reactivity based on a 4
tiered scoring system (1 to 4; TBR3 low = scores 1-2; TBR3 high = scores 3-4). Of
the 205 invasive carcinomas, 123 were luminal type (95 type A, 28 type B), 8 were
HER-2 type, and 62 were triple negative (TN). TBR3 was high in 112 (55 %) and low
in 93 (45 %) cases. Low TBR3 was associated with higher histological grade and
worse disease free and overall survival, all features of biologically aggressive
breast carcinomas. TBR3 was significantly associated with the subtype of breast
cancer, as low TBR3 was detected in 95 % of TN compared to 22 % of luminal tumors
(p < 0.0001). We discovered a significant association between low TBR3 protein
expression, TN breast cancer phenotype, and disease progression. These data
suggest that TBR3 loss might be linked to the development of TN breast cancers
and pave the way to investigating whether restoring TBR3 function may be a
therapeutic strategy against TN breast carcinomas.
PMID- 25135010
TI - Impact of antigenic diversity on laboratory diagnosis of Avian bornavirus
infections in birds.
AB - Avian bornaviruses (ABVs) are a group of genetically diverse viruses within the
Bornaviridae family that can infect numerous avian species and represent the
causative agents of proventricular dilatation disease, an often fatal disease
that is widely distributed in captive populations of parrots and related species.
The current study was designed to assess the antigenic variability of the family
Bornaviridae and to determine its impact on ABV diagnosis by employing
fluorescent antibody assays. It was shown that polyclonal rabbit sera directed
against recombinant bornavirus nucleoprotein, X protein, phosphoprotein, and
matrix protein provided sufficient cross-reactivity for the detection of viral
antigen from a broad range of bornavirus genotypes grown in cell culture. In
contrast, a rabbit anti-glycoprotein serum and 2 monoclonal antibodies directed
against nucleoprotein and phosphoprotein proteins reacted more specifically.
Antibodies were readily detected in sera from avian patients infected with known
ABV genotypes if cells persistently infected with a variety of different
bornavirus genotypes were used for analysis. For all sera, calculated antibody
titers were highest when the homologous or a closely related target virus was
used for the assay. Cross-reactivity with more distantly related genotypes of
other phylogenetic groups was usually reduced, resulting in titer reduction of up
to 3 log units. The presented results contribute to a better understanding of the
antigenic diversity of family Bornaviridae and further emphasize the importance
of choosing appropriate diagnostic tools for sensitive detection of ABV
infections.
PMID- 25135011
TI - Foot-and-mouth disease in Asiatic black bears (Ursus thibetanus).
AB - Foot-and-mouth disease (FMD) is a highly contagious, debilitating, and globally
significant viral disease typically affecting cloven-hoofed hosts. The diagnosis
of FMD in bears in Vietnam is described. The current study describes a confirmed
case of FMD in a bear species, and the clinical signs compatible with FMD in a
Malayan sun bear. Thirteen Asiatic black bears (Ursus thibetanus) and 1 Malayan
sun bear (Helarctos malayanus) were apparently affected. In August 2011, an adult
bear became lethargic, and developed footpad vesicles. Over 15 days, 14 out of 17
bears developed similar signs; the remaining 3 co-housed bears and another 57
resident bears did not. All affected bears developed vesicles on all footpads,
and most were lethargic for 24-48 hr. Nasal and oral lesions were noted in 6 and
3 cases, respectively. Within 1 month, all looked normal. Foot-and-mouth disease
virus (FMDV) was detected by reverse transcription polymerase chain reaction,
classified as serotype O, and isolated by virus isolation techniques.
Phylogenetic analysis demonstrated clustering of 3 bear isolates, in a branch
distinct from other FMDV type O isolates. The outbreak likely occurred due to
indirect contact with livestock, and was facilitated by the high density of
captive bears. It showed that Asiatic black bears are capable of contracting FMDV
and developing clinical disease, and that the virus spreads easily between bears
in close contact.
PMID- 25135012
TI - Adoption and compliance in second-hand smoking bans: a global econometric
analysis.
AB - OBJECTIVES: We examine the determinants governing both countries' enactment of
smoking bans in public places and their ability to successfully put these bans
into effect. METHODS: Using a large sample (N = 99-184) of low-, middle- and high
income countries, econometric techniques are used to estimate the influence of
several variables on cross-national variations in the adoption and compliance of
second-hand smoke laws (2010). RESULTS: We find similarities in the determinants
of adoption and compliance. Yet more notable are the differences, with several
political economy factors which have a statistically significant influence on
countries' level of compliance with existing smoke-free laws in public places
found not to consistently influence their propensity to adopt bans in the first
place. Possible explanations for this discrepancy are that governments are
motivated to adopt smoking bans for reasons other than protecting the health of
their citizens and that the real costs of smoking bans are predominantly borne at
the compliance stage. CONCLUSIONS: More effort needs to be made to ensure that
governments realize their existing policy commitments through effective
enforcement of bans.
PMID- 25135013
TI - Electronic cigarettes: proceed with great caution.
PMID- 25135014
TI - Analysis of cardiac and pulmonary injuries resulting from an experimental
penetrating thoracic injury.
AB - BACKGROUND: This study was planned to analyze the internal and external
anatomical findings of cardiac injuries and the presence of accompanying
pulmonary injuries in intentionally inflicted thoracic injuries to swine models.
METHODS: We inflicted a penetrating heart injury in six suis domesticus female
swine models. Two cardiac injuries, one on the left paratracheal of fourth
intercostal space (ICS) and the other on the right side were inflicted on each
model by the same researcher using a 20-cm long scalpel. All animals were then
sacrificed for morphological evaluation. RESULTS: After strikes to the left
fourth ICS, external evaluation showed that 50% of the subjects suffered a single
laceration and that 33% suffered multiple lacerations. Internal evaluation showed
additional intracardiac injuries in all five subjects. However, the subject that
suffered a single laceration on the outer surface of the heart had multiple
internal injuries while another subject that had multiple outer lacerations had
only one intracardiac injury. Only three subjects suffered cardiac injuries and
only two out of those three with pulmonary injuries after right fourth
intercostal intrusions. CONCLUSION: This experiment has shown that external
evaluation of the heart tissue may not alone be sufficient to determine the
extent of cardiac injuries and accompanying pulmonary injuries caused by
penetrating thoracic injuries.
PMID- 25135015
TI - The effects of oral antibiotics on infection prophylaxis in traumatic wounds.
AB - BACKGROUND: The objective of this study is to examine the effectiveness of oral
antibiotics in the prevention of infection development in traumatic wounds.
METHODS: Forty Wistar albino rats were divided into five groups of eight animals.
After the crushed wound model was made on the back of the rats, wounds were
closed with a simple suture and Staphylococcus aureus ATCC 29213 strain was used
to create infection. All rats apart from the controls were given oral gavage with
antibiotics, including cephalexin, amoxicillin-clavulanate, clarithromycin (CAM),
or levofloxacin for 5 days. Wounds were evaluated qualitatively and
quantitatively on 5th day approximately 18 h after the last treatment. RESULTS:
In the quantitative evaluation, no infection was observed in the treatment groups
with amoxicillin-clavulanate, CAM, cephalexin, or levofloxacin. There was no
significant difference on the numbers of bacteria found in the wounds among the
groups. In terms of quantitative inflammation findings, no hyperemia or pus was
detected in the groups that were given medication. Furthermore, no statistically
significant difference was found among the groups in terms of induration.
CONCLUSION: Oral prophylactic antibiotics have been found to be effective in the
prevention of wound infection in the traumatic crushed wound model infected with
S. aureus in rats.
PMID- 25135016
TI - Correlation between arterial blood gas analysis and outcome in patients with
severe head trauma.
AB - BACKGROUND: Traumatic brain injury is one of the major concerns of global public
health, because it is the main cause of morbidity and mortality between young
people. This study aimed to investigate the possible association between the
parameters of arterial blood gas (ABG) and outcome of patients with severe head
trauma. METHODS: In this prospective study, 70 patients with severe head trauma
were studied in Urmia Imam Khomeini hospital during 18-month period of time. The
parameters of ABG were documented within the 1st hour of admission, and their
correlation was evaluated with Glasgow coma scale (GCS) and Glasgow outcome score
(GOS). These parameters also were compared between expired and discharged
patients. RESULTS: Seventy patients with severe head trauma including 60 males
(85.7%) and 10 females (14.3%) with a mean age of 34.34+/-14.82 (range: 18-76)
years were studied. The mortality rate during hospitalization was 38.6% (n=27).
There was no significant correlation between the parameters of ABG and GCS score
and GOS scores. Furthermore, there was no significant difference between the
survivors and non-survivors in terms of the mean value of ABG parameters
(p>0.05). CONCLUSION: ABG at the time of admission is not a significant predictor
of outcome in patients with severe head trauma.
PMID- 25135017
TI - Value of the Glasgow coma scale, age, and arterial blood pressure score for
predicting the mortality of major trauma patients presenting to the emergency
department.
AB - BACKGROUND: The purpose of this study is to detect the mortality predictive power
of new Glasgow coma scale, age, and arterial pressure (GAP) scoring system in
major trauma patients admitted to the emergency department (ED). METHODS: A total
of 100 major trauma patients admitted to Uludag University Faculty of Medicine ED
who were 18 years of age or more were included in the study. In this prospective
study, revised trauma score (RTS), injury severity score (ISS), trauma-related
ISS (TRISS), Mechanism, GAP (MGAP) and GAP scores of the patients were
calculated. RESULTS: A significant positive correlation was established between
ISS, TRISS, MGAP, and GAP in predicting in-hospital mortality (p<0.0001). Short
term (24 hours) and long-term (4-week) mortality prediction rates and area under
the curve in receiver operating characteristics analysis were 0.727-0.680 for
RTS, 0.863-0.816 for ISS, 0.945-0,911 for TRISS, 0.970-0.938 for MGAP, and 0.910
0.904 for GAP. All calculated trauma scoring systems revealed a significant
mortality prediction power (p<0.001). GAP score was found statistically and
significantly selective and sensitive in predicting both in-ED and in-hospital
mortality (p=0.0001). CONCLUSION: In major trauma patients, GAP score is an
easily calculable system both in the field and at the time of admission in the
EDs by providing emergency physicians with future decision-making schemes by
means of mortality prediction of the patients.
PMID- 25135018
TI - Impact of smoking on trauma patients.
AB - BACKGROUND: The harmful effects of smoking have been well-documented in the
medical literature for decades. To further the support of smoking cessation, we
investigate the effect of smoking on a less studied population, the trauma
patient. METHODS: All trauma patients admitted to the surgical intensive care
unit at the LAC + University of Southern California medical center between
January 2007 and December 2011 were included. Patients were stratified into two
groups - current smokers and non-smokers. Demographics, admission vitals,
comorbidities, operative interventions, injury severity indices, and acute
physiology and chronic health evaluation (APACHE) II scores were documented. Uni-
and multi-variate modeling was performed. Outcomes studied were mortality,
duration of mechanical ventilation, and length of hospitalization. RESULTS: A
total of 1754 patients were available for analysis, 118 (6.7%) patients were
current smokers. The mean age was 41.4+/-20.4, 81.0% male and 73.5% suffered
blunt trauma. Smokers had a higher incidence of congestive heart failure (4.2%
vs. 0.9%, p=0.007) and alcoholism (20.3% vs. 5.9%, p<0.001), but had a
significantly lower APACHE II score. After multivariate regression analysis,
there was no significant mortality difference. Patients who smoked spent more
days mechanically ventilated (beta coefficient: 4.96 [1.37, 8.55, p=0.007]).
CONCLUSION: Smoking is associated with worse outcome in the critically ill trauma
patient. On an average, smokers spent 5 days longer requiring mechanical
ventilation than non-smokers.
PMID- 25135019
TI - Etiology and prognosis of penetrating eye injuries in geriatric patients in the
Southeastern region of Anatolia Turkey.
AB - BACKGROUND: The purpose of this study was to evaluate the etiologic and
prognostic factors of open eye injuries in geriatric patients in the Southeastern
region of Anatolia. METHODS: Forty-five geriatric patients who underwent surgery
for an open eye injury in our clinic between the years of 2008 and 2012 were
evaluated retrospectively. Age, gender, cause and the mechanism of the trauma,
visual acuity (VA), and the time between the trauma and the surgery were obtained
from files and evaluated. RESULTS: The mean age of the patients was 70.4+/-8.2
(65-90) years. Thirty-four of the cases were male and 11 were female. The most
frequent mechanism of trauma was a wood strike, while the second most common one
was injury with a knife. Corneoscleral penetration was the most frequently
observed trauma. The mean VA of the patients was 2.26+/-0.65 at admission, and
was 1.53+/-0.99 logarithm of the minimum angle of resolution at the final
evaluation. The most frequent complications of trauma were iris prolapse and
hyphema. There was a significant correlation between the first and final VA.
CONCLUSION: Penetrating ocular injuries are seen less frequently among geriatric
patients, and their prognosis may be worse due to less-efficient wound site
healing and differences in scleral rigidity. The most important factor affecting
the final VA measurement was the VA of the patient at admission.
PMID- 25135020
TI - Comparison of trauma scores for predicting mortality and morbidity on trauma
patients.
AB - BACKGROUND: In this study, we compared the anatomical, and physiological scoring
systems trauma revised injury severity score (TRISS), revised trauma score (RTS),
injury severity score (ISS), new injury severity score (NISS) to each other, to
find out the most accurate and reliable trauma score for the risk classification
of morbidity and mortality among the trauma patients. METHODS: This is a cross
sectional study, which included 633 patients who admitted to our University
Hospital Emergency Department during an 8-month period due to trauma. All blunt
and penetrating traumas (traffic accident, assault, etc.) patients above 16 years
were included. RESULTS: Arrival time trauma scores (ISS, NISS, RTS, and TRISS) of
the patients was calculated. Mean trauma score for the mortality prediction was
calculated, and the p value was equal for all (p=0.001). Trauma scores were also
analyzed for the hospitalization time in intensive care unit (ICU). While NISS,
RTS, and TRISS values were significant (p=0.048, p=0.048, and p=0.017,
respectively), ISS value was not significant (p=0.257) for predicting the ICU
hospitalization time. Only TRISS was a good predictor for the mechanically
ventilation time in ICU patients (p=0.01). CONCLUSION: In conclusion, we
determined that the anatomical trauma scores (NISS, ISS) predicted the
hospitalization and ICU necessities better, whereas TRISS, an anatomo
physiological trauma score, defined the ICU hospitalization and mechanically
ventilation time better.
PMID- 25135021
TI - Experience of 80 cases with Fournier's gangrene and "trauma" as a trigger factor
in the etiopathogenesis.
AB - BACKGROUND: The purpose of the present study was to retrospectively analyze the
patients' data presented with Fournier's gangrene (FG), to compare obtained data
with the literature and to investigate the role of "trauma" in the
etiopathogenesis. METHODS: A retrospective study was conducted on 126 patients
with FG that consulted to our department. RESULTS: There were 76 male and four
female patients. The mean age of the patients was 53.5+/-13.6 years. The most
common presentation of patients was swelling (n=74). The scrotum has been shown
to be the most commonly affected area in the patients (n=75). Diabetes mellitus
was the leading predisposing factor and trauma was the leading responsible cause
for FG. Escherichia coli was the most frequently identified microorganism (n=43,
53.75%). Primary closure was the most common technique used for all patients.
Three patients exhibited a mortal course due to sepsis and multi-organ failure.
CONCLUSION: FG still has a high mortality rate. Rapid and correct diagnosis of
the disease can avoid inappropriate or delayed treatment and even death of the
patient. The healthcare professionals should be aware that any trauma in the
perineal region could lead to FG.
PMID- 25135022
TI - Management of ankle sprains during pregnancy: evaluation of 96 cases.
AB - BACKGROUND: The aim of this study was to suggest a safe management method for the
diagnosis and treatment of ankle sprains in pregnant patients. METHODS: Between
November 2005 and January 2013, 96 pregnant patients with ankle sprains referred
to the department of orthopedics and traumatology were evaluated,
retrospectively. The Ottawa ankle rules were used to assess the need for
radiologic evaluation. Radiological procedures: Surface USG, X-ray (0,6 mGy,
mortise view), MRI (T1 and STIR) and fluoroscopy with 0,8 mGy/s doses 0,4 ms
single shot views in surgery room. The results of the operated patients were
evaluated with AOFAS scoring system. RESULTS: Forty-four (45,8%) patients were
treated with conservative methods and there was no need for radiological
evaluation. USG was used in 17 (17,7%), MRI in 24 (25%), X-ray in 4 (4,1%) and
both USG and MRI in 7 (7,2%) patients during diagnosis. An algorithm was created
for the diagnosis and treatment of pregnant patients with ankle sprains. No
complications due to radiological and surgical procedures occurred over
pregnancies. The AOFAS score was 83 (65-100) in the operated patients.
CONCLUSION: There is no standard management method for the diagnosis and
treatment of pregnant patients with ankle sprains. The algorithm presented in
this study may be useful. Good results can be obtained with an appropriate
preparation and surgical technique.
PMID- 25135023
TI - Retrospective analysis of burn injuries caused by hot milk in 159 pediatric
patients: 14 years of experience in a burn unit.
AB - BACKGROUND: The aim of this study was to investigate the hot milk burns among the
pediatric patients and to compare our experiences with similar studies in the
literature. METHODS: A 14-year retrospective study was conducted on 159 pediatric
patients with hot milk burn who hospitalized at the Burn Unit of Erciyes
University Medical Faculty. RESULTS: There were 81 male and 78 female patients
with a male to female ratio of 1.03:1. The mean age of the patients was 2.7+/-1.6
years. The initial injury was immersion in 59.7% of the patients and spillage in
40.3%. The mean burned body surface area of the patients was 18.6+/-10.8%. Twenty
two percent of the patients had moderate, and 78% had major burn trauma. Forty
nine percent of the patients received burn wound debridement and reconstruction
with auto-skin grafts. Our burn unit's mortality rate was 1.5% among 542
pediatric patients with hot water, and 5.6% among 159 pediatric patients with hot
milk burn during the same period, respectively. CONCLUSION: Hot milk burns should
be considered as separately from other hot liquid burns which do not contain fat
such as water, tea, and coffee. Physical and chemical properties of milk because
of its high content of fat give rise to more tissue destruction, increased
morbidity and mortality.
PMID- 25135024
TI - [The results of low profile locking anatomical plate application for the
treatment of Edinburg type 2 clavicle diaphysis fractures].
AB - BACKGROUND: Although conservative measures are the general choice of treatment
for clavicle fractures; surgery is advised for displaced and multifragmentary
fractures. Open reduction and osteosynthesis with a plate-screw combination are
used widely as surgical treatment options. METHODS: In our study, there were 21
patients with Edinburgh Type IIB clavicle middiaphysal fractures treated
surgically with locked anatomical clavicle plate. RESULTS: Among those 31
patients and 32 clavicle middiaphysal fractures, Seventeen clavicle fractures
were right-side, and fifteen were left side. 24 of them were males, 7 of them
were females and the mean age was 28 (15-62) years. The mean follow-up period was
12.3 (6-36) months and healing time 15.2 (12-20) weeks. 3 patients with Type IIB
fracture had a healing time longer than 12 weeks. As the result of healing
patients', mean constant score was 92 (85-98) and DASH score 9 (2-20). There has
been a problem due to the implant detected in 3 (9%) patients. DISCUSSION:
Successful functional and radiographic results can be achieved as a result of the
surgical treatment of the clavicle middiaphysal fractures with locked anatomical
plates.
PMID- 25135025
TI - Ergotamine-induced vasospastic ischemia mimicking arterial embolism: unusual
case.
AB - Ergotamine toxicity is an important and rare condition, including tachycardia,
arterial spasm which occurring as a result of accidental overdosing or drug
interactions. We assessed the consequences of delayed diagnosis of peripheral
arterial vasoconstriction occurring after simultaneous macrolide use by a 35-year
old woman using an ergot-derived drug for migraine. Diagnosis of ergotamine
intoxication begins with suspicion. Interventional radiologists and surgeons
should be aware of this acute dangerous condition.
PMID- 25135026
TI - Successful surgical rescue of delayed onset diaphragmatic hernia following
radiofrequency ablation for hepatocellular carcinoma.
AB - Radiofrequency ablation (RFA) has been established as the mainstay therapy for
hepatocellular carcinoma (HCC) in patients deemed unsuitable for surgical
resection. However, delayed diaphragmatic hernia can occur as a result of this
procedure. There have been only seven other cases reported on this complication
in the literature. Considering the recent growth in the popularity of the
procedure, it is predictable that the incidence of the diaphragmatic hernia, due
to RFA, will definitely increase. This case report is therefore vitally important
as it increases clinical awareness of this currently rare complication, which
could lead to improved survival rates in these patients. This case concerns an 81
year-old Asian man with a past medical history of cirrhosis and HCC (segment IV
and VIII) who presented with a delayed, right diaphragmatic hernia and
strangulated ileus 18 months after his original RFA procedure. It is important to
implement extra measures to limit the risk of diaphragmatic, thermal injuries
when RFA is performed. In particular, gastroenterologists, surgeons and accident
and emergency staff should all be aware of this complication proceed with rapid
diagnosis and management when patients, who previously underwent RFA, present
with acute abdominal pain.
PMID- 25135027
TI - Surgical treatment of a Malgaigne fracture.
AB - Sacral fractures are generally accompanied by pelvic ring fractures. They rarely
develop in an isolated form. Sacroiliac dislocation without sacral fracture is
extremely rare. We report a case with a sacroiliac dislocation without sacral
fracture, which was treated surgically. Lumbopelvic stabilization was applied
using iliac wing plates. The case was evaluated according to his clinical
condition and visual analogue score (VAS), American Spinal Injury Association
(ASIA) and Oswestry scales. Considering the role of the sacrum, which transmits
the load of the entire spine to the pelvis, meticulous care must be given to
ensure the mechanic stability of the spine when evaluating patients with sacral
and pelvic fractures. Very serious spinopelvic instability is present in
sacroiliac dislocations even in the absence of sacral fractures. Caudal migration
of the sacrum together with the cranial migration of the iliac wings can cause
serious pelvic imbalance and difficulties in walking and maintaining a standing
position. Aggressive stabilization and fusion are required, and these must be
performed in the early period.
PMID- 25135028
TI - Thyroid storm due to head injury.
AB - In this case report, we would like to present a 36-year-old male patient injured
in a street fight without any disease previously known, who was accepted to our
intensive care unit with the preliminary diagnoses of minimal cerebral contusion
and aspiration pneumonia however by the physical examination, clinical and
laboratory findings, was diagnosed as thyroid storm due to trauma. In the current
literature, only a few cases reported showing thyroid storm-induced by trauma,
and we would like to present the clinical features and management of this life
threatening endocrinological emergency.
PMID- 25135029
TI - Swallowed a needle stuck in heart.
AB - Cardiac tamponade (CT) is a clinical entity characterized by hemodynamic
insufficiency resulting from increased intrapericardial pressure due to
accumulation of contents such as serous fluid, blood, and pus. CT is a treatable
cause of cardiogenic shock, which can be fatal unless diagnosed promptly.
Dyspnea, chest pain, hypotension, tachycardia, pulsus paradoxus, raised jugular
venous pressure, muffled heart sounds, decreased electrocardiographic voltage,
and enlarged cardiac silhouette on chest X-ray are the major clinical signs in
CT. Idiopathic or viral pericardititis, iatrogenic trauma during percutaneous
coronary interventions or coronary artery bypass grafting, external trauma,
malignancies, acute or chronic kidney disease, collagen vascular diseases,
tuberculosis, radiation on the chest wall, hypothyroidism and aortic dissection
are the etiologic factors. Herein, we present a case of surgically treated CT,
which was diagnosed in the third day of ingestion of a sewing needle.
PMID- 25135030
TI - [Cross stability in conventional shoes by the use of spring steel insoles: a
pedobarographic effect study with observational application].
AB - BACKGROUND: From an orthopedic point of view, wearing conventional ready to wear
shoes negatively affects the front transverse arch of the human foot by forcing
it into an unnatural inverted position. OBJECTIVES: The aim of the present
orthopedic application study was to conduct a standardized assessment of the
biomechanical effect of a newly developed, longitudinally flexible and cross
stable spring steel insole by means of pedobarographic measurements and by means
of a supplementary questioning of the participants. MATERIAL AND METHODS: In
order to do this a total of 33 healthy adult participants were recruited in
summer 2013. The randomized, blinded and controlled main study compared the cross
stable insole made from spring steel with a flat, ordinary control insole made
from ethylene vinyl acetate by means of pedobarographic in-shoe measurements at
the forefoot. Additionally, the subjectively perceived effect of the steel insole
with respect to comfort, restricted mobility and pain was assessed in a
randomized, blinded and controlled ancillary study, using a cross-over design.
RESULTS: Both the plantar peak pressure and the plantar force-time integral were
significantly higher with the spring steel insole, especially in the central
forefoot. In the subsequent test phase lasting several weeks during which the
participants were asked to wear the spring steel insole, they rarely complained
about problems and in particular did not report negative effects regarding
comfort, restricted mobility and pain compared to the ordinary control insoles.
CONCLUSION: The present study was conducted according to high methodological
standards and proved for the first time that the tested spring steel insoles have
a positive effect on the human forefoot. The cross stability increases the
pressure in the median ball area, prevents the unnatural inverted position of the
forefoot and thus creating an effect which is comparable to walking barefoot. As
the participants did not judge this orthopedic effect of the cross stability as
being uncomfortable, such an insole could be used a millionfold as a primary
prevention in conventional shoes.
PMID- 25135031
TI - Prevalence of tinea pedis in psoriasis, compared to atopic dermatitis and normal
controls--a prospective study.
AB - There are discrepancies in the literature regarding the prevalence of tinea pedis
in psoriasis. The aim of this investigation was to conduct a cross-sectional
study of the prevalence of tinea pedis in psoriasis compared to atopic dermatitis
patients and normal controls. We enrolled 232 psoriatic patients, 190 atopic
dermatitis patients and 202 normal controls, between the years 2010 and 2013. The
prevalence of tinea pedis was 13.8% in psoriasis patients, not significantly
different from that in atopic dermatitis patients 8.4% (P = 0.092)), but
significantly higher than in normal controls 7.4% (P = 0.043). Both gender and
age affected the prevalence of tinea pedis in psoriasis and normal controls,
while only age affected the prevalence of tinea pedis in atopic dermatitis.
Regarding gender, there was higher prevalence of tinea pedis in men: 19.1% (P =
0.019) in psoriasis and 12.1% (P = 0.013) in normal controls. Age affected the
prevalence of tinea pedis in normal controls (P < 0.001), psoriasis patients (P =
0.001) and atopic dermatitis patients (P = 0.001), with higher prevalence with
increasing age. Trichophyton rubrum was the most common species in psoriasis
(71.9%), atopic dermatitis (75.0%) and normal controls (73.3%). Our study found a
relatively high prevalence of tinea pedis among psoriasis patients.
PMID- 25135032
TI - Fentanyl sublingual spray for breakthrough pain in cancer patients.
AB - Breakthrough pain is a transient exacerbation of pain that occurs either
spontaneously, or in relation to a specific predictable or unpredictable trigger,
despite relatively stable and adequately controlled background pain. Typically,
breakthrough pain has a fast onset and short duration, and a significant impact
on patients' quality of life. Normal-release oral opioids are the traditional
pharmacological approach for patients who are receiving an around the clock
opioid regimen; however, their onset and duration of action may not be suitable
for treating many breakthrough pains. Efforts to provide nonparenteral opioid
formulations that could provide more rapid, and more effective, relief of
breakthrough pain have led to the development of transmucosal opioid formulations
including fentanyl sublingual spray (FSLS). This is a formulation of fentanyl
available in doses of 100, 200, 400, 600, and 800 MUg strengths approved for the
management of breakthrough pain in adult cancer patients already receiving and
who are tolerant to opioid therapy for their underlying persistent cancer pain.
Published pharmacokinetic, efficacy, tolerability, and safety data suggest that
FSLS has a valuable role to play in the symptomatic pharmacological management of
breakthrough pain. The effective dose of FSLS is determined by titration
according to the needs of the individual patient.
PMID- 25135033
TI - Review of lidocaine/tetracaine cream as a topical anesthetic for dermatologic
laser procedures.
AB - There are multiple different topical anesthetic options available to minimize the
pain associated with cosmetic dermatologic procedures. These options, either
alone or in combination, have diverse profiles for effectiveness, ease of use,
application time, need for occlusion, and side effects. The lidocaine/tetracaine
cream (Pliaglis((r)), Galderma Laboratories, Texas, USA), one of the newer
combination options, offers effective pain alleviation that has been evaluated in
numerous clinical trials. This combination anesthetic is associated with a very
favorable profile because of its ease of use and mild side effects compared to
other topical local anesthetics. An overview of available topical local
anesthetics will be provided with an outline of clinical study characteristics
and results regarding the use of lidocaine/tetracaine cream.
PMID- 25135035
TI - Randomized study of pregabalin in patients with cancer-induced bone pain.
AB - INTRODUCTION: Improvements are needed in the management of cancer-induced bone
pain (CIBP). The objective of this study was to assess the efficacy and safety of
pregabalin compared with placebo in the adjunctive treatment of patients with
moderate to severe CIBP who were receiving opioids. METHODS: In this randomized,
double-blind, placebo-controlled, parallel-group, multicenter trial, 152 adults
diagnosed with a malignant, solid tumor with metastases to bone were randomized
to flexible-dose pregabalin (100, 150, 300, or 600 mg/day) or placebo, as add-on
to stable opioid analgesic therapy, which was optimized prior to the start of the
study. The primary efficacy endpoint was the duration-adjusted average change
(DAAC) from baseline in the daily worst pain at the reference site (measured by
11-point numeric rating scale [NRS]) during the fixed-dosage phase. The study was
terminated early following an interim analysis that indicated an increase in
sample size would be needed to satisfy statistical assumptions for the primary
endpoint. Given the early termination of the study, only descriptive analyses
were performed. RESULTS: The mean (standard deviation) DAAC from baseline in NRS
score for the primary endpoint favored pregabalin treatment: -1.53 (1.81) in the
pregabalin group and -1.23 (1.74) in the placebo group. Mean DAAC for average
pain and sleep interference (NRS) also favored pregabalin. More patients treated
with pregabalin reported improvement ("very much improved," "much improved," or
"minimally improved") based on Patient Global Impression of Change: 81.4%
compared with 70.0% in the placebo group. CONCLUSION: Data from this study
indicate that pregabalin use may reduce metastatic bone pain. Due to the
incomplete analysis, further study of pregabalin in the management of CIBP is
required.
PMID- 25135036
TI - Predictive value of lidocaine for treatment success of oxcarbazepine in patients
with neuropathic pain syndrome.
AB - INTRODUCTION: Pharmacotherapy in patients with neuropathic pain syndromes (NPS)
can be associated with long periods of trial and error before reaching
satisfactory analgesia. The aim of this study was to investigate whether a short
intravenous (i.v.) infusion of lidocaine may have a predictive value for the
efficacy of oxcarbazepine. METHODS: In total, 16 consecutive patients with NPS
were studied in a prospective, uncontrolled, open-label study design. Each
patient received i.v. lidocaine (5 mg/kg) within 30 min followed by a long-term
oral oxcarbazepine treatment (900-1,500 mg/day). During an observation period of
28 days, treatment response was documented by a questionnaire including the
average daily pain score documented on a numeric rating scale (NRS). RESULTS: A
total of 6 out of 16 patients (38%) were lidocaine responders (defined as pain
reduction >50% during the infusion), and 4 of 16 (25%) were oxcarbazepine
responders. In total, 6 out of 16 participants (38%) discontinued oxcarbazepine
treatment due to side effects. In an interim analysis predictive value of the
lidocaine infusion was low with a Kendall's tau correlation coefficient of 0.29
and coefficient of determination R(2) of 0.119 (95% confidence interval -0.29 to
0.72). As a consequence of this low correlation, the study was discontinued for
ethical reasons. CONCLUSION: In conclusion, lidocaine infusion has a low
predictive value for effectiveness of oxcarbazepine-if at all.
PMID- 25135034
TI - Myofascial pain syndrome: a treatment review.
AB - Myofascial pain syndrome (MPS) is defined as pain that originates from myofascial
trigger points in skeletal muscle. It is prevalent in regional musculoskeletal
pain syndromes, either alone or in combination with other pain generators. The
appropriate evaluation and management of myofascial pain is an important part of
musculoskeletal rehabilitation, and regional axial and limb pain syndromes. This
article reviews the current hypotheses regarding the treatment modalities for
myofascial trigger points and muscle pain. Through a critical evidence-based
review of the pharmacologic and nonpharmacologic treatments, the authors aim to
provide clinicians with a more comprehensive knowledge of the interventions for
myofascial pain.
PMID- 25135037
TI - Effects of a single session group intervention for pain management in chronic
pain patients: a pilot study.
AB - INTRODUCTION: Behavioral and psychological interventions are key components of
treating chronic pain. However, there are logistical barriers to providing such
treatments, including a lack of psychological staff to provide such interventions
and limited ability of patients with chronic pain to attend multiple sessions. As
other areas of mental health have shown promise in providing single session
interventions for various conditions, this pilot study hypothesized that a single
group session for chronic pain patients could be helpful in decreasing patient
pain catastrophizing. The five content areas addressed in the group were termed
understanding, accepting, calming, balancing, and coping. METHODS: A pilot study
was undertaken. Chronic pain patients were given a pre-group assessment,
including the Pain Catastrophizing Scale with a follow-up assessment administered
3 months later. RESULTS: Fifty-three patients were studied. Results showed a
significant decrease in overall pain catastrophizing scores at follow-up. A clear
majority of patients also reported that the group was helpful and should be
offered to other pain patients. CONCLUSION: This study suggests that a single
session group can be a helpful intervention for patients with chronic pain.
PMID- 25135039
TI - Erratum to: Review of Lidocaine/Tetracaine Cream as a Topical Anesthetic for
Dermatologic Laser Procedures.
PMID- 25135038
TI - Interpreting effect sizes and clinical relevance of pharmacological interventions
for fibromyalgia.
AB - Duloxetine, milnacipran, and pregabalin are approved by the United States Food
and Drug Administration for the management of fibromyalgia. A number of meta
analyses, pooled analyses, and systematic reviews have been published in recent
years involving the efficacy of these three medications for pain in fibromyalgia.
Despite being based on the same clinical data, some analyses found these
treatments to have a clinically relevant effect on pain, while others concluded
that the advantages were small or of questionable clinical relevance. This
commentary discussed possible reasons behind these differing conclusions and
explored ways of evaluating the clinical relevance of pharmacological treatments
for fibromyalgia. In particular, we considered: (1) the importance of judicious
and careful interpretation of average treatment effect size and the recognition
that average treatment effect sizes do not always tell the whole story; (2) the
utility of individual patient response data to assess clinical relevance; and (3)
the importance of considering pain reduction within the context of other benefits
due to the presence of associated symptoms in patients with fibromyalgia.
PMID- 25135040
TI - Transcutaneous vagal nerve stimulation may elicit anti- and pro-nociceptive
effects under experimentally-induced pain - a crossover placebo-controlled
investigation.
AB - Vagal nerve stimulation is a promising method for the treatment of pain. The aim
was to investigate the effect of non-invasive transcutaneous vagal nerve
stimulation (TVNS) on the experimental pain threshold (PT) and to compare it with
placebo. PT of standardized electrical stimulation was measured in 22 healthy
male volunteers during two study sessions. TVNS was applied to the auricular
concha bilaterally for 35min using 2Hz/100Hz bursts with the intensity, which was
individually maximal but non-painful. During the placebo session, the volunteers
received no stimulation. PT, heart rate and blood pressure were registered as
outcome measures. There were no differences in PT values between TVNS and placebo
conditions in the group analysis. Fifteen volunteers (responders) reacted with an
increase in PT during TVNS (p<0.01 vs. baseline) but not during the placebo
session. Another six participants reported decreased PT during and after TVNS
(p<0.05 vs. baseline), but not during the placebo session. Heart rate and blood
pressure did not change during the study. Transcutaneous vagal nerve stimulation
may produce both anti- and pro-nociceptive effects in healthy volunteers. The
individual sensitivity and TVNS parameters might play a role.
PMID- 25135041
TI - [Epigenetic modifications in autoimmune diseases].
PMID- 25135042
TI - [Obituary for Prof. Dr. med. Fritz Schilling (1919-2014)].
PMID- 25135044
TI - Infectious Endocarditis in 49-Year-Old Man and Discussion of Phenotypic
Characteristics of Aerococcus urinae and Viridans Streptococci.
AB - PATIENT: 49 year-old man. CHIEF COMPLAINT: Dyspnea at rest and dyspnea on
exertion. HISTORY OF PRESENT ILLNESS: Diagnosed with upper respiratory tract
infection 10 days previously. PAST MEDICAL HISTORY: Obese (BMI not available),
but no significant past medical history. SOCIAL HISTORY: Noncontributory. FAMILY
HISTORY: Noncontributory.
PMID- 25135046
TI - Writing style: abstract thoughts.
PMID- 25135045
TI - First report of bacteremia by Janibacter terrae in humans.
AB - The genus Janibacter comprises nine different species mainly found in the
environment. Only two human infections by these microorganisms have been
previously reported, one by J. melonis and another one by an undescribed
Janibacter sp. Herewith we report the first human cases of infection by J. terrae
in four bacteremic patients. The microorganisms were isolated from two
consecutive blood cultures taken from four febrile patients with several
underlying conditions. All patients were treated with antibiotics, two of them
with favorable outcome. Two severely immunocompromised patients died, and one was
treated with an antibiotic in vitro active against the isolate. Janibacter terrae
was identified by phenotypic and 16S rDNA amplification methods. This report
includes also the first data on antimicrobial susceptibility of this
opportunistic pathogen. Clinical microbiologists should be aware of this
microorganism which can be identified by phenotypic and molecular methods.
PMID- 25135047
TI - Biomarkers in atopic dermatitis: it is time to stratify.
PMID- 25135048
TI - Profibrotic agents for venous malformations?
PMID- 25135049
TI - Epidemiology of hand eczema from adolescence to adulthood.
PMID- 25135054
TI - FeP nanoparticles grown on graphene sheets as highly active non-precious-metal
electrocatalysts for hydrogen evolution reaction.
AB - A synthetic route to FeP-GS hybrid sheets that show good stability and high
electrocatalytic activity for hydrogen evolution reaction is reported. The
materials are prepared via thermal phosphidation of pre-synthesized Fe3O4-GS
hybrid sheets.
PMID- 25135053
TI - Patient perspective on remote monitoring of cardiovascular implantable electronic
devices: rationale and design of the REMOTE-CIED study.
AB - BACKGROUND: Remote patient monitoring is a safe and effective alternative for the
in-clinic follow-up of patients with cardiovascular implantable electronic
devices (CIEDs). However, evidence on the patient perspective on remote
monitoring is scarce and inconsistent. OBJECTIVES: The primary objective of the
REMOTE-CIED study is to evaluate the influence of remote patient monitoring
versus in-clinic follow-up on patient-reported outcomes. Secondary objectives are
to: 1) identify subgroups of patients who may not be satisfied with remote
monitoring; and 2) investigate the cost-effectiveness of remote monitoring.
METHODS: The REMOTE-CIED study is an international randomised controlled study
that will include 900 consecutive heart failure patients implanted with an
implantable cardioverter defibrillator (ICD) compatible with the Boston
Scientific LATITUDE(r) Remote Patient Management system at participating centres
in five European countries. Patients will be randomised to remote monitoring or
in-clinic follow-up. The In-Clinic group will visit the outpatient clinic every 3
6 months, according to standard practice. The Remote Monitoring group only visits
the outpatient clinic at 12 and 24 months post-implantation, other check-ups are
performed remotely. Patients are asked to complete questionnaires at five time
points during the 2-year follow-up. CONCLUSION: The REMOTE-CIED study will
provide insight into the patient perspective on remote monitoring in ICD
patients, which could help to support patient-centred care in the future.
PMID- 25135055
TI - Synthesis of benzimidazole[2.1-b][1,3]oxazine spirooxindoles via three-component
reaction of N-benzylbenzimidazole, acetylenedicarboxylates, and N-alkylisatins.
AB - The three-component reaction of N-benzylbenzimidazole, dialkyl
acetylenedicarboxylate, and N-alkylisatins in tetrahydrofuran at room temperature
afforded the novel functionalized benzimidazole[2.1-b][1,3]oxazine spirooxindoles
in good yields. (1)H NMR spectra indicated that two diastereoisomers with a ratio
of 1:3-1:6 exist in the obtained spirooxindole derivatives.
PMID- 25135056
TI - Neurophysiological assessment of the injured spinal cord: an intraoperative
approach.
AB - STUDY DESIGN: Prospective, observational study. OBJECTIVES: To assess the spinal
cord function intraoperatively in subjects during spine stabilization for spinal
cord trauma, by recording muscular (m-MEPs) and epidural motor evoked potentials
(e-MEPs, D wave) along with cortical and epidural somatosensory evoked potentials
(e-SEPs) and predicting the outcome of spinal cord injury (SCI). SETTING:
Regional Trauma Center, Torino, Italy. METHODS: Fifty-five patients were
intraoperatively studied during posterior spine stabilization surgery for
traumatic SCI. In all, 21 of these had complete SCI, 14 an incomplete SCI-6 of
them with central cord syndrome and 1 with central cord plus Brown Sequard
syndrome-and 20 patients were neurologically uncompromised. RESULTS: The
neurophysiologic profile of the complete SCI was the absence of both m-MEPs and e
MEPs caudally to the lesion site, associated with a lack of cortical and e-SEPs
cranially to the lesion site. None of these patients recovered motor function in
the follow-up. A clearly detectable caudal D wave was associated with motor
recovery even in deeply paraparetic patients. In one neurologically incomplete
patient a reversible deterioration of m-MEPs and e-MEPs was observed during the
compression-distraction manoeuvre. CONCLUSION: Intraoperative neurophysiological
evaluation of SCI patients can provide information about spinal cord function
that is not retrievable by other clinical means and can correctly predict
neurological outcome. Intraoperative testing during early stabilization of the
spine of deeply paraparetic SCI patients provides additional information about
their neurological profile.
PMID- 25135057
TI - Use of screening to recruitment ratios as a tool for planning and implementing
spinal cord injury rehabilitation research.
AB - STUDY DESIGN: Descriptive report. OBJECTIVES: To describe screening to
recruitment (S:R) ratios and discuss their use for planning and implementing
research among individuals with spinal cord injury (SCI) . SETTING: Toronto,
Ontario, Canada. METHODS: We calculated S:R ratios for SCI research by study
methodology and nature of the exposure/intervention for 25 studies previously
conducted in a tertiary SCI rehabilitation facility. Study methodologies included
ten randomized controlled trials (RCTs), nine cohort studies and six panel
studies. Exposures included seven rehabilitation interventions, and three drug
studies, ten telephone interviews/chart abstractions (TI/CA) and five surveys. A
S:R ratio was calculated for each study methodology, and exposure type, by
dividing the number of consenting individuals who underwent screening by the
number of eligible recruited participants enrolled in the study. RESULTS: In
terms of design, RCTs had the highest median S:R ratio (3:1), followed by cohort
studies (2:1) and panel studies (2:1). In terms of intervention type, drug
studies had the largest median S:R ratio (5:1), followed in descending order by
rehabilitation studies (2:1), TI/CAs studies (2:1) and surveys (2:1).
CONCLUSIONS: Reported S:R ratios varied substantially with study methodology and
the associated study intervention exposure. Awareness of S:R ratios may assist
researchers in estimating recruitment timelines, personnel needs and study
budgets for a required sample size based on the planned study methodology and
intended study exposure. We advocate for the routine reporting of S:R ratios to
inform the success of future SCI research.
PMID- 25135059
TI - GFR may not accurately predict aspects of proximal tubule drug handling.
AB - PURPOSE: Dose modification in renal impairment has traditionally been based on
changes in estimated glomerular filtration rate (eGFR; estimated by creatinine
clearance). However, many drugs are eliminated by tubular anionic and cationic
transport where changes in eGFR may not necessarily reflect changes in tubular
function. This study investigated the relationship between GFR and renal tubular
function with reference to drug handling by using accepted drug probes. METHODS:
Three drug probes, (51)Cr-EDTA, fluconazole, and pindolol, were administered to
patients who had varying degrees of renal impairment. Blood sampling, assays, and
a pharmacokinetic analysis were performed for all drug probes and endogenous
urate. Measured GFR ((51)Cr-EDTA clearance; mGFR) was compared to tubular anionic
transport (urate clearance), tubular reabsorption (fluconazole clearance), and
tubular cationic transport (S-pindolol clearance). RESULTS: A moderately strong
association was demonstrated between the measured isotopic GFR and creatinine
clearance (R(2) = 0.78). A moderate positive correlation was found between mGFR
and proximal tubular anion transport and reabsorption (R(2) = 0.40-0.44, p <
0.0001). In contrast, cationic secretion correlated poorly with mGFR (R(2) =
0.11, p = 0.036). CONCLUSIONS: Given that drug dosing schedules utilise eGFR
values as the basis for modifying drug dosing, our results would suggest that a
recommendation of a dose reduction according to eGFR alone should be treated with
caution.
PMID- 25135058
TI - Deglycosylation of mAb by EndoS for improved molecular imaging.
AB - PURPOSE: Monoclonal antibodies (mAbs) have been shown preclinically as reliable
targeting moieties for antigen imaging using near-infrared fluorescence (NIRF)
molecular imaging. However, crystallizable fragment-gamma receptor (FcgammaRs)
expressed on immune cells also bind mAbs through defined epitopes on the constant
fragment (Fc) of IgG. Herein, we evaluate the potential impact Fc interactions
have on mAb agent imaging specificity. PROCEDURE: Through the removal of
conserved glycans within the Fc domain, shown to have Fc/FcgammaR interactions,
we evaluate their impact on non-specific binding/accumulation of a NIRF-labeled
mAb-based imaging agent in lymph nodes (LNs) in inflamed animals and in an
orthotopic prostate cancer animal model of LN metastasis. RESULTS:
Deglycosylation of a murine mAb against the human epithelial cell adhesion marker
using endoglycosidase EndoS significantly reduced non-specific binding in the LNs
of inflamed animals and in cancer-negative LNs of tumor-bearing animals.
Sensitivity remained unchanged while improvement in imaging specificity increased
imaging accuracy. CONCLUSION: The reduction of non-specific binding through
deglycosylation of a mAb-based imaging agent shows that reducing Fc/FcgammaR
interactions can improve imaging accuracy.
PMID- 25135060
TI - Efficacy and safety of creatine supplementation in childhood-onset systemic lupus
erythematosus: a randomized, double-blind, placebo-controlled, crossover trial.
AB - INTRODUCTION: Creatine supplementation has emerged as a promising non
pharmacological therapeutic strategy to counteract muscle dysfunction and low
lean mass in a variety of conditions, including in pediatric and rheumatic
diseases. The objective of this study was to examine the efficacy and safety of
creatine supplementation in childhood systemic lupus erythematosus (C-SLE).
METHODS: C-SLE patients with mild disease activity (n = 15) received placebo or
creatine supplementation in a randomized fashion using a crossover, double-blind,
repeated-measures design. The participants were assessed at baseline and after 12
weeks in each arm, interspersed by an eight-week washout period. The primary
outcomes were muscle function, as assessed by a battery of tests including one
maximum repetition (1-RM) tests, the timed-up-and-go test, the timed-stands test,
and the handgrip test. Secondary outcomes included body composition, biochemical
markers of bone remodeling, aerobic conditioning, quality of life, and physical
capacity. Possible differences in dietary intake were assessed by three 24-hour
dietary recalls. Muscle phosphorylcreatine content was measured through
phosphorus magnetic resonance spectroscopy (31 P-MRS). The safety of the
intervention was assessed by laboratory parameters, and kidney function was
measured by (51)Cr-EDTA clearance. Additionally, self-reported adverse events
were recorded throughout the trial. RESULTS: Intramuscular phosphorylcreatine
content was not significantly different between creatine and placebo before or
after the intervention (creatine-Pre: 20.5 +/- 2.6, Post: 20.4 +/- 4.1, placebo
Pre: 19.8 +/- 2.0; Post: 20.2 +/- 3.2 mmol/kg wet muscle; p = 0.70 for
interaction between conditions). In addition, probably as a consequence of the
lack of change in intramuscular phosphorylcreatine content, there were no
significant changes between placebo and creatine for any muscle function and
aerobic conditioning parameters, lean mass, fat mass, bone mass, and quality of
life scores (p > 0.05). The (51)Cr-EDTA clearance was not altered by creatine
supplementation and no side effects were noticed. CONCLUSION: A 12-week creatine
supplementation protocol at 0.1 g/kg/d is well tolerated and free of adverse
effects but did not affect intramuscular phosphorylcreatine, muscle function,
free-fat mass or quality of life in non-active C-SLE patients. TRIAL
REGISTRATION: Clinicaltrials.gov number: NCT01217320.
PMID- 25135061
TI - Oral pigmentation is a specific feature of lupus erythematosus.
PMID- 25135062
TI - Intramyocardial injection of hypoxia-preconditioned adipose-derived stromal cells
treats acute myocardial infarction: an in vivo study in swine.
AB - Hypoxic preconditioning is a promising method for improving the anti-apoptotic
and paracrine signaling capabilities of adipose-derived stromal cells (ADSCs).
The purpose of this study was to analyze the influence of different hypoxic
conditions on ADSCs and the therapeutic effects of hypoxia-preconditioned ADSCs
(HPADSCs) on an animal model of myocardial infarction (MI). For the in vitro
studies, ADSCs were divided into five groups and cultured in different oxygen
concentrations (1, 3, 5, 10, and 21 %). After 24 h, RT-PCR and western blots
showed that 3 % oxygen preconditioning could improve the viability and cytokine
secretion of the ADSCs. A Matrigel assay indicated that the HPADSC-conditioned
medium could stimulate endothelial cells to form capillary-like tubes. For the in
vivo studies, MI was induced by coronary occlusion in 24 mature Chinese minipigs.
The animals were divided into three groups and treated by intramyocardial
injection with vehicle alone (saline group), with 1 * 10(8) ADSCs cultured in
normoxic conditions (ADSCs group) or with 1 * 10(8) ADSCs precultured in 3 %
oxygen (HPADSCs group). SPECT and echocardiography demonstrated that cardiac
function was improved significantly in the HPADSC transplant group compared with
the vehicle control group (P < 0.05). Immunofluorescence showed fewer apoptotic
cells and more small- to medium-sized vessels in the HPADSC transplantation group
(P < 0.05). Three percent oxygen is the optimum preconditioning treatment for
ADSCs. HPADSC transplantation can prevent ventricular remodeling and reduce the
infarct size.
PMID- 25135065
TI - The mechanism of Menshutkin reaction in gas and solvent phases from the
perspective of reaction electronic flux.
AB - The mechanism of Menshutkin reaction, NH(3) + CH(3)Cl = [CH(3)-NH(3)]+ + Cl-, has
been thoroughly studied in both gas and solvent (H(2)O and cyclohexane) phase. It
has been found that solvents favor the reaction, both thermodynamically and
kinetically. The electronic activity that drives the mechanism of the reaction
was identified, fully characterized, and associated to specific chemical events,
bond forming/breaking processes, by means of the reaction electronic flux. This
led to a complete picture of the reaction mechanism that was independently
confirmed by natural bond-order analysis and the dual descriptor for chemical
reactivity and selectivity along the reaction path.
PMID- 25135066
TI - Accurate calculation of the ionization energies of the chlorine lone pairs in
1,1,1-trifluoro-2-chloroethane (HCFC-133a).
AB - The vertical ionization energies of the chlorine lone pairs in HCFC-133a have
been calculated at the SCF (via Koopmans' theorem and including orbital
relaxation) and correlated (ROMP2, OVGF, and ROCCSD(T)) levels. Dunning aug-cc
pVXZ (X = D, T, and Q) basis sets were employed, and the ROMP2 and ROCCSD(T)
results were extrapolated to the complete basis set (CBS) limit. Our highest
level results (obtained at the ROCCSD(T)/CBS level) were 11.99 and 12.08 eV for
the Cl lone pairs of A" and A' symmetry, respectively. The values obtained at the
computationally much less demanding ROMP2/CBS level were just 0.10 and 0.13 eV
higher than the highest-level ones. Using the Cl lone-pair band of the
photoelectron spectrum of the HCF(2)Cl and CF(3)Cl molecules as a guide, it is
considered very unlikely that these two lone pairs can be discriminated in the
photoelectron spectrum of the title molecule. The use of the calculated IPs to
estimate the energies of the Rydberg states of HCFC-133a is also discussed.
PMID- 25135064
TI - The MyPEEPS randomized controlled trial: a pilot of preliminary efficacy,
feasibility, and acceptability of a group-level, HIV risk reduction intervention
for young men who have sex with men.
AB - An exigent need exists for HIV prevention intervention research targeting young
men who have sex with men (MSM)-a group of young adults that, despite composing
the highest and most racially disproportionate rates of HIV incidence, have been
least often the focus of behavioral intervention research. This pilot study
tested a group-based HIV primary prevention intervention for young MSM to
evaluate its initial efficacy, feasibility, and acceptability. Participants were
randomized (N = 101; aged 16-20 years) to one of two group-level, HIV and STI
education programs: controls participated in a non-interactive, lecture-based
program, while intervention participants took part in a highly interactive
program tailored to young MSM aged 16-20. Sexual risk and social cognitive
outcomes were assessed at baseline, 6-, and 12-weeks post-intervention. Over the
entire follow-up period, intervention participants were less likely than controls
to engage in any sexual behavior while under the influence of substances (p <
.05), and a decreasing trend in unprotected anal sex while under the influence of
substances was also observed in this group (p = .08). Follow-up differences
between groups on social cognitive outcomes favored the intervention group,
though these differences were non-significant. Acceptability ratings were modest.
A 6-session behavioral intervention tailored to young MSM, aged 16-20, is
feasible, acceptable, and demonstrates evidence of preliminary efficacy in
reducing sexual risk, specifically sexual risk while under the influence of
substances.
PMID- 25135067
TI - Conformational analysis of glutamic acid: a density functional approach using
implicit continuum solvent model.
AB - Amino acids are constituents of proteins and enzymes which take part almost in
all metabolic reactions. Glutamic acid, with an ability to form a negatively
charged side chain, plays a major role in intra and intermolecular interactions
of proteins, peptides, and enzymes. An exhaustive conformational analysis has
been performed for all eight possible forms at B3LYP/cc-pVTZ level. All possible
neutral, zwitterionic, protonated, and deprotonated forms of glutamic acid
structures have been investigated in solution by using polarizable continuum
model mimicking water as the solvent. Nine families based on the dihedral angles
have been classified for eight glutamic acid forms. The electrostatic effects
included in the solvent model usually stabilize the charged forms more. However,
the stability of the zwitterionic form has been underestimated due to the lack of
hydrogen bonding between the solute and solvent; therefore, it is observed that
compact neutral glutamic acid structures are more stable in solution than they
are in vacuum. Our calculations have shown that among all eight possible forms,
some are not stable in solution and are immediately converted to other more
stable forms. Comparison of isoelectronic glutamic acid forms indicated that one
of the structures among possible zwitterionic and anionic forms may dominate over
the other possible forms. Additional investigations using explicit solvent models
are necessary to determine the stability of charged forms of glutamic acid in
solution as our results clearly indicate that hydrogen bonding and its type have
a major role in the structure and energy of conformers.
PMID- 25135068
TI - Investigations into the nature of halogen- and hydrogen-bonding interactions of
some heteroaromatic rings with dichlorine monoxide.
AB - We have studied the structures, properties, and nature of halogen- and hydrogen
bonding interactions between some heteroaromatic rings (C(5)H(5)N, C(4)H(4)O, and
C(4)H(4)S) with Cl(2)O at the MP2/aug-cc-pVTZ level. We also considered the
solvent effect on the halogen bonds and hydrogen bonds in the C(5)H(5)N-Cl(2)O
complexes and found that the solvent has a weakening effect on the pi-type
halogen bond and hydrogen bond but a prominent enhancing effect on sigma-type
halogen bond. The complexes have also been analyzed with symmetry adapted
perturbation theory method (SAPT).
PMID- 25135069
TI - Current resources for evidence-based practice, September/October 2014.
PMID- 25135071
TI - Insight into curcumin-loaded beta-lactoglobulin nanoparticles: incorporation,
particle disintegration, and releasing profiles.
AB - This study aimed at developing protein nanoparticles with desirable loading
efficiency (LE) and low cross-linker concentration. Using beta-lactoglobulin
(BLG) and curcumin as a model system, this work demonstrated that the LE could be
improved by up to 157% by maintaining low antisolvent content before mild
evaporation. Moreover, the optimal level of glutaraldehyde decreased by 50% as
the curcumin/protein ratio increased, suggesting that toxic cross-linkers could
be partly replaced with natural phenols such as curcumin. The BLG-curcumin
nanoparticles showed average size of 164-214 nm, zeta potential of -42 mV, and LE
of up to 11%. Interestingly, BLG nanoparticles demonstrated rapid disintegration
and nutraceutical release in simulated gastric fluid (SGF) at pH 2, despite the
known resistance of BLG against pepsin. However, they maintained integrity in SGF
at pH 5. This phenomenon, followed by extensive degradation in simulated
intestinal fluid, suggested the controlled-release property of BLG nanoparticles
when administered orally.
PMID- 25135070
TI - A malaria vaccine candidate based on an epitope of the Plasmodium falciparum RH5
protein.
AB - BACKGROUND: The Plasmodium falciparum protein RH5 is an adhesin molecule
essential for parasite invasion of erythrocytes. Recent studies show that anti
PfRH5 sera have potent invasion-inhibiting activities, supporting the idea that
the PfRH5 antigen could form the basis of a vaccine. Therefore, epitopes
recognized by neutralizing anti-PfRH5 antibodies could themselves be effective
vaccine immunogens if presented in a sufficiently immunogenic fashion. However,
the exact regions within PfRH5 that are targets of this invasion-inhibitory
activity have yet to be identified. METHODS: A battery of anti-RH5 monoclonal
antibodies (mAbs) were produced and screened for their potency by inhibition of
invasion assays in vitro. Using an anti-RH5 mAb that completely inhibited
invasion as the selecting mAb, affinity-selection using random sequence peptide
libraries displayed on virus-like particles of bacteriophage MS2 (MS2 VLPs) was
performed. VLPs were sequenced to identify the specific peptide epitopes they
encoded and used to raise specific antisera that was in turn tested for
inhibition of invasion. RESULTS: Three anti-RH5 monoclonals (0.1 mg/mL) were able
to inhibit invasion in vitro by >95%. Affinity-selection with one of these mAbs
yielded a VLP which yielded a peptide whose sequence is identical to a portion of
PfRH5 itself. The VLP displaying the peptide binds strongly to the antibody, and
in immunized animals elicits an anti-PfRH5 antibody response. The resulting
antisera against the specific VLP inhibit parasite invasion of erythrocytes more
than 90% in vitro. CONCLUSIONS: Here, data is presented from an anti-PfRH5 mAb
that completely inhibits erythrocyte invasion by parasites in vitro, one of the
few anti-malarial monoclonal antibodies reported to date that completely inhibits
invasion with such potency, adding to other studies that highlight the potential
of PfRH5 as a vaccine antigen. The specific neutralization sensitive epitope
within RH5 has been identified, and antibodies against this epitope also elicit
high anti-invasion activity, suggesting this epitope could form the basis of an
effective vaccine against malaria.
PMID- 25135072
TI - Canadian Society for Exercise Physiology position stand: Benefit and risk for
promoting childhood physical activity.
AB - Current guidelines recommend children accumulate 60 min of daily physical
activity; however, highly publicized sudden-death events among young athletes
raise questions regarding activity safety. An expert group convened (June 2012)
to consider the safety of promoting increased physical activity for children, and
recommended the publication of an evidence-based statement of current knowledge
regarding the benefits and risks of physical activity for children.
Recommendations for encouraging physical activity while maximizing the
opportunity to identify children who have been prescribed a physical activity
restriction include (1) professionals and (or) researchers that encourage
children to change the type of physical activity or to increase the frequency,
intensity, or duration of their activity should inquire whether a child has
primary healthcare provider-prescribed activity limitations before the child's
activity participation changes; (2) physical activity researchers should
prioritize the development of evidence regarding the benefits and risks of
childhood physical activity and inactivity, particularly data on the risks of
sedentary lifestyles and physical activity-associated injury risks that accounts
for the amount of activity performed, and the effectiveness of current risk
management strategies and screening approaches; (3) professionals and researchers
should prioritize the dissemination of information regarding the benefits of
physical activity and the risks of sedentary behaviour in children; and (4)
parents and professionals should encourage all children to accumulate at least 60
min of physical activity daily. The recommendations are established as a minimum
acceptable standard that is applicable to all physical activity opportunities
organized for children, whether those opportunities occur in a community, school,
or research setting.
PMID- 25135073
TI - Summary report of the International Association of Neurorestoratology VII
Conference: regulations, ethics, science, and the need of patients care in
neurorestoratology.
PMID- 25135075
TI - Experimental evaluation of a Markov multizone model of particulate contaminant
transport.
AB - The performance of a Markov chain model of the three-dimensional transport of
particulates in indoor environments is evaluated against experimentally measured
supermicrometer particle deposition. Previously, the model was found to replicate
the predictions of relatively simple particle transport and fate models; and this
work represents the next step in model evaluation. The experiments modeled were
(i) the release of polydispersed particles inside a building lobby, and (ii) the
release of monodispersed fluorescein-tagged particles inside an experimental
chamber under natural and forced mixing. The Markov model was able to reproduce
the spatial patterns of particle deposition in both experiments, though the model
predictions were sensitive to the parameterization of the particle release
mechanism in the second experiment. Overall, the results indicate that the Markov
model is a plausible tool for modeling the fate and transport of supermicrometer
particles.
PMID- 25135074
TI - Perceived neighbourhood social cohesion and myocardial infarction.
AB - BACKGROUND: The main strategy for alleviating heart disease has been to target
individuals and encourage them to change their health behaviours. Although
important, emphasis on individuals has diverted focus and responsibility away
from neighbourhood characteristics, which also strongly influence people's
behaviours. Although a growing body of research has repeatedly demonstrated
strong associations between neighbourhood characteristics and cardiovascular
health, it has typically focused on negative neighbourhood characteristics. Only
a few studies have examined the potential health enhancing effects of positive
neighbourhood characteristics, such as perceived neighbourhood social cohesion.
METHODS: Using multiple logistic regression models, we tested whether higher
perceived neighbourhood social cohesion was associated with lower incidence of
myocardial infarction. Prospective data from the Health and Retirement Study--a
nationally representative panel study of American adults over the age of 50--were
used to analyse 5276 participants with no history of heart disease. Respondents
were tracked for 4 years and analyses adjusted for relevant sociodemographic,
behavioural, biological and psychosocial factors. RESULTS: In a model that
adjusted for age, gender, race, marital status, education and total wealth, each
SD increase in perceived neighbourhood social cohesion was associated with a 22%
reduced odds of myocardial infarction (OR=0.78, 95% CI 0.63 to 0.94. The
association between perceived neighbourhood social cohesion and myocardial
infarction remained even after adjusting for behavioural, biological and
psychosocial covariates. CONCLUSIONS: Higher perceived neighbourhood social
cohesion may have a protective effect against myocardial infarction.
PMID- 25135076
TI - An empirical analysis of thermal protective performance of fabrics used in
protective clothing.
AB - Fabric-based protective clothing is widely used for occupational safety of
firefighters/industrial workers. The aim of this paper is to study thermal
protective performance provided by fabric systems and to propose an effective
model for predicting the thermal protective performance under various thermal
exposures. Different fabric systems that are commonly used to manufacture thermal
protective clothing were selected. Laboratory simulations of the various thermal
exposures were created to evaluate the protective performance of the selected
fabric systems in terms of time required to generate second-degree burns. Through
the characterization of selected fabric systems in a particular thermal exposure,
various factors affecting the performances were statistically analyzed. The key
factors for a particular thermal exposure were recognized based on the t-test
analysis. Using these key factors, the performance predictive multiple linear
regression and artificial neural network (ANN) models were developed and
compared. The identified best-fit ANN models provide a basic tool to study
thermal protective performance of a fabric.
PMID- 25135078
TI - Review of neurodevelopmental treatment.
PMID- 25135077
TI - Calprotectin (S100A8/9) as serum biomarker for clinical response in proof-of
concept trials in axial and peripheral spondyloarthritis.
AB - INTRODUCTION: Biomarkers complementing clinical evaluations may help to reduce
the length and size of proof-of-concept (PoC) trials aimed to obtain quick "go/no
go" decisions in the clinical development of new treatments. We aimed to identify
and validate serum biomarkers with a high sensitivity to change upon effective
treatment in spondyloarthritis (SpA) PoC trials. METHODS: The candidate
biomarkers high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6),
pentraxin-3 (PTX-3), alpha-2-macroglobulin (alpha-2-MG), matrix metalloproteinase
3 (MMP-3), calprotectin, and vascular endothelial growth factor (VEGF) were
determined by enzyme-linked immunosorbent assay (ELISA) in healthy controls (n =
20) and SpA patients before and after 2 weeks of infliximab (n = 18) or placebo
(n = 19) treatment in cohort 1. Clinical outcome was evaluated at week 12.
Results were validated in ankylosing spondylitis (AS) with infliximab (cohort 2,
n = 21) and peripheral SpA with etanercept (cohort 3, n = 20). RESULTS: Serum
levels of calprotectin, hs-CRP, PTX-3, VEGF (all P < 0.001) and MMP-3 (P =
0.062), but not IL-6 and alpha-2-MG, were increased in SpA versus healthy
controls. Treatment with infliximab, but not placebo, significantly decreased
calprotectin (P < 0.001) and hs-CRP (P < 0.001) levels, with a similar trend for
MMP-3 (P = 0.063). The standardized response mean (SRM), which reflects the
ability to detect changes over time, was high for calprotectin (-1.26), good for
hs-CRP (-0.96) and moderate for MMP-3 (-0.52). Calprotectin and hs-CRP, but not
MMP-3, were good biomarkers for treatment response in axial and peripheral SpA as
evaluated and confirmed in cohort 2 and 3 respectively. CONCLUSIONS: Calprotectin
and hs-CRP are good serum biomarkers with high sensitivity to change upon
effective treatment at the group level in small-scale, short term PoC trials in
SpA.
PMID- 25135079
TI - The biology of pulmonary aspergillus infections.
AB - Pulmonary aspergillus infections are mainly caused by Aspergillus fumigatus and
can be classified based on clinical syndromes into saphrophytic infections,
allergic disease and invasive disease. Invasive pulmonary aspergillosis,
occurring in immunocompromised patients, reflects the most serious disease with a
high case-fatality rate. Patients with cystic fibrosis and severe asthma might
develop allergic bronchopulmonary aspergillosis, while saphrophytic infections
are observed in patients with lung cavities mainly due to tuberculosis.
Histopathologically, a differentiation can be made into angio-invasive and airway
invasive disease. If the host response is too weak or too strong, Aspergillus
species are able to cause disease characterized either by damage from the fungus
itself or through an exaggerated inflammatory response of the host, in both
situations leading to overt disease associated with specific clinical signs and
symptoms. The unraveling of the specific host - Aspergillus interaction has not
been performed to a great extent and needs attention to improve the management of
those clinical syndromes.
PMID- 25135083
TI - Diagnostics in prosthetic joint infections.
AB - Prosthetic joint infection (PJI) poses a significant burden on patients,
clinicians and the healthcare economy. Although various tests have been
established for the diagnosis of PJI, the diagnosis remains challenging. In this
review, established and potential future diagnostic tests are presented, some of
which could provide stepping stones towards improved diagnosis, identification of
aetiological agents and efficacious therapeutic options for the management of
PJI.
PMID- 25135080
TI - Combination of BMP2 and MSCs significantly increases bone formation in the rat
arterio-venous loop model.
AB - INTRODUCTION: In this study the induction of bone formation in an axially
vascularized bone matrix using mesenchymal stem cells (MSCs) and application of
bone morphogenetic protein 2 (BMP2) was analyzed in the arteriovenous loop (AVL)
model. MATERIALS AND METHODS: An AVL was created in the medial thigh of 42 rats
and placed in a porous titanium chamber filled with a particulated porous
hydroxyapatite and beta-tricalcium phosphate matrix and fibrin. In group A the
fibrin was loaded with 5*10(6) DiI-stained fibrin gel-immobilized primary MSCs
from syngenic Lewis rats, in group B the matrix was loaded with 60 MUg/mL BMP2
and in group C both, BMP2 and MSCs were applied at implantation time point. After
6 and 12 weeks, specimens were investigated by means of histological,
morphometrical, and micro-computed tomography analysis. RESULTS: After
implantation of an AVL a dense vascular network was visible in all groups. In
group A, newly generated bone islands were detected in the periphery of the main
vascular axis. Using BMP2 alone (group B), small islands of newly formed bone
were visible evenly distributed in all parts of the constructs. In group C nearly
the whole matrix was interspersed with bone formations. In all groups there was
an increase of bone formation between the 6 and 12 weeks explantation time
points. CONCLUSIONS: This study demonstrates for the first time the successful
generation of axially vascularized bone substitutes using MSCs and BMP2 in the
AVL rat model using a one step procedure. Using the combination of BMP2 and MSCs
there was a significant increase of bone formations detectable compared to the
BMP2 or MSCs alone groups.
PMID- 25135081
TI - A program to identify prognostic and predictive gene signatures.
AB - BACKGROUND: The advent of high-throughput technologies to profile human tumors
has generated unprecedented insight into our molecular understanding of cancer.
However, analysis of such high dimensional data is challenging and requires
significant expertise which is not routinely available to many cancer
researchers. RESULTS: To overcome this limitation, we developed a freely
accessible and user friendly Program to Identify Molecular Signatures (PIMS).
Importantly, such signatures allow important insight into cancer biology, as well
as provide clinical tools to identify potential biomarkers that might provide
means to accurately stratify patients into different risk or treatment groups. We
evaluated the performance of PIMS by identifying and testing predictive and
prognostic gene signatures for breast cancer, using multiple breast tumor
microarray cohorts representing hundreds of patients. Importantly, PIMS
identified signatures classified patients into high and low risk groups with at
least similar performance to other commonly used gene signature selection
techniques. CONCLUSIONS: Our program is contained entirely within a Microsoft
Excel file and therefore requires no installation of any additional programs or
training. Hence, PIMS provides an accessible tool for cancer researchers to
identify predictive and prognostic gene signatures to advance their research.
PMID- 25135084
TI - Molecular techniques for diagnosing prosthetic joint infections.
AB - Prosthetic joint infections (PJI) can be broadly classed into two groups: those
where there is a strong clinical suspicion of infection and those with clinical
uncertainty, including 'aseptic loosening'. Confirmation of infection and
identification of the causative organism along with provision of antibiotic
susceptibility data are important stages in the management of PJI. Conventional
microbiological culture and susceptibility testing is usually sufficient to
provide this. However, it may fail due to prior antimicrobial treatment or the
presence of unusual and fastidious organisms. Molecular techniques, in particular
specific real-time and broad-range PCR, are available for diagnostic use in
suspected PJI. In this review, we describe the techniques available, their
current strengths, limitations and future development. Real-time pathogen
specific and broad-range PCR (with single sequence determination) are suitable
for use as part of the routine diagnostic algorithm for clinically suspected PJI.
Further development of broad-range PCR with high-throughput (next-generation)
sequencing is necessary to understand the microbiome of the prosthetic joint
further before this technique can be used for routine diagnostics in clinically
unsuspected PJI, including aseptic loosening.
PMID- 25135085
TI - The clinical presentation of prosthetic joint infection.
AB - Prosthetic joint infection (PJI) complicates ~1% of arthroplasties but accounts
for considerable morbidity. Both the timing and features of PJI can vary widely.
Patients may present with early (<=3 months post-operatively), delayed (3-24
months) or late disease (>24 months). They may be acutely unwell with systemic
signs of sepsis or describe only a chronically painful joint with or without
sinus formation. Diagnostic criteria as proposed by the Infectious Diseases
Society of America and the Musculoskeletal Infection Society highlight the
importance of joint sampling to obtain histological and robust microbiological
evidence. Staphylococcus aureus and coagulase-negative staphylococci account for
>50% of infections. Early infections are likely to have been acquired intra- or
peri-operatively, whereas late infection is usually haematogenous in origin.
Acute joint inflammation suggests the presence of intra-articular free-living
bacteria, whereas chronic infections are associated with the formation of biofilm
at the bone-cement or bone-prosthesis interface. The most significant risk
factors predisposing to PJI are previous operation on the index joint, previous
arthroplasty at a different site, American Society of Anesthesiologists' grade 2,
3 or 4, body mass index >25, malignancy and procedure duration <2 or >4 h.
PMID- 25135086
TI - Clinical guidelines in the management of prosthetic joint infection.
AB - Clinical practice guidelines for the diagnosis and management of prosthetic joint
infection have been produced by a range of organizations. Guidelines stress the
importance of multi-disciplinary working and of adopting a methodical approach.
This includes careful assessment of the patient's surgical, medical and
psychosocial problems, rational investigation, a decision-making framework for
surgery and targeted, sometimes prolonged, use of intravenous or highly
bioavailable oral antibiotics. Despite limited high-quality evidence, adoption of
clinical guidelines can improve practice by reducing variation and by
establishing conditions for the subsequent conduct of multicentre studies or
systematic reviews.
PMID- 25135087
TI - Prosthetic joint infection: managing infection in a bionic era.
AB - There is increasing demand for prosthetic joint surgery and patients are becoming
more challenging due to an ageing population often with comorbidities and
immunosuppression. While prosthetic joint infection (PJI) rates are generally
low, infection can be catastrophic for the patient and hence prevention of
infection is critical. Infection, when it does occur, is further complicated by
the global rise in antimicrobial resistance. This article introduces a series of
papers on the epidemiology of PJI, its diagnosis, use of novel inflammatory
markers and molecular techniques, clinical presentation, importance of biofilms,
treatment guidelines and, finally, various strategies and novel antibiotic
treatment regimens.
PMID- 25135088
TI - Impact of bacterial biofilm on the treatment of prosthetic joint infections.
AB - Microbial biofilm contributes to chronic infection and is involved in the
pathogenesis of prosthetic joint infections. Biofilms are structurally complex
and should be considered a dynamic system able to protect the bacteria from host
defence mechanisms and from antibacterial agents. Despite the use of antibiotics
recognized as effective against acute infections, prosthetic joint infections
require long-term suppressive treatment acting on adherent bacteria. Conventional
in vitro susceptibility testing methods are not suitable for biofilm-associated
infections given that these tests do not take into account the physiological
parameters of bacterial cells in vivo. Most anti-staphylococcal drugs are able to
inhibit in vitro the adhesion of bacteria to a surface, considered to be the
first step in biofilm formation. Recent studies suggest that the lack of activity
of antibiotics against biofilm-embedded bacteria seems to be more related to the
decreased effect of the drug on the pathogen than to the poor penetration of the
drug into the biofilm. Eradication of biofilm-embedded bacteria is a very
difficult task and combination therapy is required in the treatment of persistent
infections involving biofilm. Although several combinations demonstrate potent
efficacy, rifampicin is the most common partner drug of effective combinations
against staphylococcal biofilms. Considering the complexity of biofilm-related
infections, further studies are needed to assess the activity of new therapeutic
agents in combination with antibiotics (quorum-sensing inhibitors, biofilm
disruptors and specific anti-biofilm molecules).
PMID- 25135089
TI - Current antibiotic management of prosthetic joint infections in Italy: the 'Udine
strategy'.
AB - The rate of prosthetic joint infections followed and cured at our institution is
constantly increasing, in line with epidemiological data from the recent
literature. This is probably related to the greater number of knee and hip
prostheses implanted every year. For intermediate and late infections, only the
two-stage approach is applied, as this demonstrates the best outcome in our
experience. Particular attention is paid to microbiological isolation of the
pathogen: multiple samples of tissue are collected during the interventions, and
kept in culture for a longer period of time than usual. Sonication of prosthetic
devices is used to enhance the sensitivity and specificity of the microbiological
cultures. Histological examination influences surgical choices either towards
implantation of a new prosthesis or replacement of the spacer. An empirical
antibiotic backbone of a glycopeptide/lipopeptide and rifampicin is chosen, due
to the leading role of Gram-positive bacteria in this setting and the high
incidence of methicillin resistance in our centre (>30%), followed by an
antibiotic regimen containing linezolid. If specific risk factors are present, an
anti-Gram-negative drug is added to the regimen. Duration of therapy depends upon
the approach that is chosen, usually being 6 weeks when the prosthesis is
removed. Despite at the moment being limited by its small sample size, data from
our experience confirms that our empirical approach may represent a valid choice
during the early phase of treatment, by keeping linezolid for a step-down therapy
of shorter duration (4 weeks).
PMID- 25135090
TI - Clinical experience with linezolid for the treatment of orthopaedic implant
infections.
AB - Gram-positive cocci are commonly isolated in orthopaedic implant infections and
their resistance to beta-lactams and fluoroquinolones is increasing. The high
oral bioavailability of linezolid makes it an attractive oral alternative to
glycopeptides and its use has increased in the last decade. To evaluate
experience with linezolid in orthopaedic implant infections a systematic review
of the literature available in English was undertaken. Only those articles
describing series of >=10 patients with acute or chronic orthopaedic implant
infections treated with linezolid and with a clear definition of diagnosis and
outcome were selected. A total of 293 patients (79.9% had prosthetic joint
infections) were analysed in the 10 articles included. The overall remission rate
with at least 3 months of follow-up was 79.9%, depending on whether the implant
was removed or not (94% versus 69.9%). The addition of rifampicin was described
in only two articles and no significant difference was observed. Adverse events
were frequent during prolonged administration of linezolid (34.3%), requiring
treatment discontinuation in 12.8%. The most common event was anaemia (13.4%)
followed by gastrointestinal symptoms (11.1%). In conclusion, linezolid seems a
good oral treatment alternative for orthopaedic implant infections due to Gram
positive cocci resistant to beta-lactams and fluoroquinolones. However, close
monitoring of adverse events is required.
PMID- 25135091
TI - Epidemiology and burden of prosthetic joint infections.
AB - Whilst improvements in patient care have reduced the risk of infection in
patients undergoing prosthetic joint surgery, the substantial and growing number
of hip and knee arthroplasty procedures undertaken translates into a continued
and potentially increasing burden on patients, healthcare providers and the wider
economy. Increases in patient obesity will raise further challenges to prevention
efforts given the associated elevated risk of infection. Ongoing monitoring of
infection rates remains a critical means to identify and address local and
national changes in the epidemiology of prosthetic joint infection and to assess
the impact of interventions.
PMID- 25135092
TI - Vitamin D: a new player in kidney transplantation?
AB - Vitamin D is a hormone with pleiotropic effects. It mainly regulates calcium and
phosphate metabolism through interactions with FGF23 and its receptor klotho. In
addition, it has been shown that Vitamin D also regulates the immune response and
has protective effects from cardiovascular disease, cancer and infections. Most
renal transplant recipients have overt Vitamin D deficiency, a condition that may
be associated with a decline in graft function and other complications. After
kidney transplantation, elevated levels of FGF23 may predict increased risks of
death and allograft loss. Theoretically, an optimal Vitamin D supplementation
might favor operational tolerance and protect transplant recipients from the
triad cardiovascular disease-cancer-infection. However, more solid data are
needed to confirm this and to set the optimal level of serum Vitamin D
supplementation in order to attain the best clinical outcome.
PMID- 25135093
TI - Agriculture.
PMID- 25135094
TI - Global travel.
PMID- 25135096
TI - Identifying risk factors of musculoskeletal disorders on Korean farms.
AB - BACKGROUND: Farming is known to pose musculoskeletal disorder risk factors,
although how risk factors differ between farmers in various countries is largely
unknown. OBJECTIVE: To identify ergonomic risk factors through a qualitative
assessment of common tasks performed by South Korean farmers. METHODS: A
convenience sample of Korean farmers was videotaped performing typical jobs on
farms that produced rice, fruits and vegetables, or raised animals. Ergonomists
identified poor ergonomic risk factors that may lead to musculoskeletal disorders
including poor postures of the shoulders, wrists, neck, low back, and knees.
RESULTS: Severe flexion and lifting of heavy loads was common across farms. While
many of the concerning risk factors identified were similar to those in other
parts of the world, one was unique in this population - deep knee flexion while
weeding, harvesting, and sorting. CONCLUSIONS: Given the Korean farm population
is aging at an alarming rate and remains dominated by small farms, many of these
potential risk factors may have a continued or increased role in the development
of musculoskeletal disorders. While the current study provided the first
observational assessment of ergonomic demands on Korean farms, more quantitative
and rigorous investigations are needed to establish actual risk factors.
PMID- 25135097
TI - A randomized intervention trial to reduce mechanical exposures in the Colombian
flower industry.
AB - BACKGROUND: Evidence on effectiveness of ergonomic interventions to reduce
mechanical demands of the upper extremity is scarce in agriculture. OBJECTIVE: To
conduct an ergonomic intervention to reduce mechanical exposures on workers
during manual flower cutting, while emphasizing postural education and reduction
of force requirements. PARTICIPANTS: Seventy seven workers (20 to 55 years old;
80% women) from six companies that cultivate roses participated in this study.
METHODS: Participants from three companies were randomly assigned to control and
intervention groups. A postural education program and a maintenance program was
designed and implemented in the intervention group aiming to achieve more neutral
postures of the wrist and forearm and to reduce force requirements during rose
cutting. Changes in self-reported effort and upper extremity postures, kinematics
and muscular activity between baseline and follow-up assessments were evaluated.
RESULTS: Most of the observed changes in the evaluated mechanical exposures were
moderate for both groups. The intervention group showed differential improvements
compared to the control group for 95th percentile forearm pronation (intervention
group went from 50.6 to 35.6 degrees ; control group went from 18.4 to 34.7
degrees ); and to some degree for the maximum wrist radial deviation (the
intervention group went from 17 degrees to 7.6 degrees ; control group went from
10.1 degrees to 7.8 degrees ). Also, the mean elbow flexion for the control
group was reduced from 62.3 to 48.4 degrees , whereas it increased from 52.2 to
57.3 degrees in the intervention group. No differential changes between the
intervention and control groups were observed for the kinematic variables, except
for an unexpected reduction in the 95th percentile velocity of wrist flexion
extension in the control group, which was not observed in the intervention group.
Lastly, although observed changes in muscular activity were not statistically
significant, improvements were observed for the intervention group for the flexor
and extensor carpi radialis and the flexor carpi ulnaris; although the opposite
was true for the extensor carpi ulnaris. CONCLUSIONS: Important although
sometimes mixed results were achieved with this field intervention, focusing on
postural and force requirement demands. The positive results are encouraging
considering the presence of typical limitations observed in field intervention
studies.
PMID- 25135099
TI - Better understanding of bariatric surgery outcomes through sleep.
PMID- 25135100
TI - Is systemic inflammation not involved in endoscopic duodenal-jejunal bypass liner
induced diabetes remission?
PMID- 25135101
TI - Validating a new computed tomography atlas for grading ankle osteoarthritis.
AB - As the most common joint disease, osteoarthritis (OA) poses a significant source
of pain and disability. It can be defined by classic radiographic findings,
particular symptoms, or a combination of the 2. Although specific grading scales
have been developed to evaluate OA in various joints, such as the shoulder, hip,
and knee, no definitive classification system is available for grading OA in the
ankle. The purpose of the present study was to create and validate a standardized
atlas for grading (or staging) ankle osteoarthritis using computed tomography
(CT) and "hallmark" findings noted on coronal, sagittal, and axial views
extrapolated from the Kellgren-Lawrence radiographic scale. The CT scans of 226
patients at the Miami Veterans Affairs Medical Center were reviewed. An atlas was
derived from a retrospective review of 30 remaining CT scans taken from July 2008
to November 2011. After this review, 3 orthogonal static CT images, obtained from
11 remaining patients, were chosen to represent the various stages on the OA
scale and were used to test the validity of the atlas developed by 2 of us
(M.M.C. and N.D.V.). A multispecialty panel of 9 examiners, excluding ourselves,
independently rated the 11 CT scan subjects. The differences among examiners and
specialties were calculated, including an intra-examiner agreement for 2 separate
readings spaced 9 months apart. Although the small number of subspecialty
examiners made the intraspecialty comparisons difficult to validate, the findings
nevertheless indicated excellent agreement among all specialty groups, with good
intra-investigational (intraclass correlation coefficient 0.962 and 1) inter
investigational (intraclass correlation coefficient 0.851) values. These results
appeared to validate the CT ankle OA atlas, which we believe will be a valuable
clinical and research tool, one that will likely be more beneficial than less
relevant generalized OA grading scales in use today.
PMID- 25135102
TI - A large-scale study on epidemiology and risk factors for chronic ankle
instability in young adults.
AB - Up to 40% of ankle sprains can result in chronic ankle instability (CAI). The
prevalence of CAI and its association with body mass index (BMI) and height in
the general young adult population has not been reported. The database records of
young adults before recruitment into mandatory military service were studied.
Information on the disability codes associated with CAI was retrieved. Logistic
regression models were used to assess the association between the BMI and body
height with various grades of CAI severity. The study cohort included 829,791
subjects (470,125 males and 359,666 females). The prevalence was 0.7% for mild
CAI and 0.4% for severe instability in males and 0.3% and 0.4%, respectively, for
females (p < .001). An increased BMI was associated with ankle instability in
males (overweight, odds ratio [OR] 1.249, p < .001; obese, OR 1.418, p < .001)
and females (overweight, OR 1.989 p < .001; obese, OR 2.754, p < .001). The body
height was associated with an increased risk of CAI when the highest height
quintile was compared with the lowest height quintile in both males (OR 2.443, p
< .001) and females (OR 1.436, p < .001) for all levels of instability severity.
The present study has shown a greater prevalence of CAI among males than females
in a general healthy young adult population. CAI was associated with an increased
BMI and greater body height for all grades of instability severity.
PMID- 25135103
TI - Treatment of an open medial tibiotalar dislocation with no associated fracture.
AB - Tibiotalar dislocations without associated fractures are very uncommon in adults,
and only a few studies have been published regarding this injury. More than 50%
of these dislocations will be posteromedial, with a high incidence of open
injuries, and 25% are pure posterior dislocations. In the present report, we
discuss our experience and management of a medial tibiotalar dislocation with no
associated fracture. In the present case, the patient was brought to the
operating room on presentation to our facility and underwent irrigation and
debridement with primary closure of his wound. He was immobilized
postoperatively. The patient tolerated the operation well and did not sustain any
postoperative complications. He was able to regain function of the injured
extremity until he was lost to follow-up. Regarding treatment, the surgery should
be speedy, gentle to the soft tissue, and with as little implanted material as
possible. Although we do not advocate that our management and treatment of this
injury become the standard, the present case provides a good example of some of
the challenges often encountered when treating these injuries.
PMID- 25135104
TI - Pedal Gangrenous Changes in the Digits of an Adolescent With Ulcerative Colitis:
A Case Report.
AB - Ulcerative colitis is an autoimmune inflammatory disease of the colon and is
occasionally associated with thrombosis. We report the case of an adolescent with
ulcerative colitis who presented with bilateral gangrenous toes without signs of
ascending cellulitis. Radiographs indicated the presence of bilateral and erosive
changes in the distal phalanges. The vascular team referred the patient for
podiatric intervention for distal vasculitis and thrombosis of the digital
vessels. Transphalangeal amputations were performed, and postoperative
antibiotics were initiated. The surgical sites healed uneventfully, and the
patient was able to resume daily activities. Thrombosis of the foot in the
context of ulcerative colitis is a rare, but serious, complication that can lead
to serious comorbidities, including amputation.
PMID- 25135105
TI - Isolated Fifth Metatarsocuboid Coalition: A Case Report.
AB - Isolated tarsometatarsal coalitions are extremely rare, and the previous 5
documented cases involved the first and third metatarsocuneiform joints. We
report the case of a 69-year-old female with symptomatic fifth metatarsocuboid
coalition associated with ipsilateral varus-type ankle osteoarthritis and
instability. The patient was successfully treated by arthrodesis of the fifth
metatarsocuboid joint, resection of the hypertrophied tuberosity of the fifth
metatarsal, advancement of the peroneus brevis tendon, opening wedge distal
tibial osteotomy, and calcaneal displacement osteotomy. After 1 year, 6 months,
she was able to walk well, although she complained of minor discomfort under the
fifth metatarsal base, which resolved with the use of protective padding.
Radiographs at this stage confirmed consolidation of both the arthrodesis and the
osteotomy sites. Although isolated fifth metatarsocuboid coalition is less likely
to be encountered than other tarsal coalitions, it can sometimes be painful
enough to necessitate surgery.
PMID- 25135106
TI - Holocene variations in peatland methane cycling associated with the Asian summer
monsoon system.
AB - Atmospheric methane concentrations decreased during the early to middle Holocene;
however, the governing mechanisms remain controversial. Although it has been
suggested that the mid-Holocene minimum methane emissions are associated with
hydrological change, direct evidence is lacking. Here we report a new independent
approach, linking hydrological change in peat sediments from the Tibetan Plateau
to changes in archaeal diether concentrations and diploptene delta(13)C values as
tracers for methanogenesis and methanotrophy, respectively. A minimum in inferred
methanogenesis occurred during the mid-Holocene, which, locally, corresponds with
the driest conditions of the Holocene, reflecting a minimum in Asian monsoon
precipitation. The close coupling between precipitation and methanogenesis is
validated by climate simulations, which also suggest a regionally widespread
impact. Importantly, the minimum in methanogenesis is associated with a maximum
in methanotrophy. Therefore, methane emissions in the Tibetan Plateau region were
apparently lower during the mid-Holocene and partially controlled by interactions
of large-scale atmospheric circulation.
PMID- 25135107
TI - Bilateral lens luxation and intracapsular lens extractions in a Matshchie's tree
kangaroo.
AB - An adult, female, captive, Matshchie's tree kangaroo was diagnosed with an
anterior lens luxation in the right eye and a lens subluxation in the left eye.
Both eyes were treated surgically with intracapsular lens extractions. A 360
degrees rhegmatogenous retinal detachment was diagnosed 6 months postoperatively
in the left eye. Aphakic vision was maintained in the right eye 9 months
postoperatively. Based on family history and the lack of antecedent ocular
disease, the lens luxations were presumed to be inherited and veterinarians
should be aware of this condition within the captive tree kangaroo population.
PMID- 25135108
TI - Giant seborrheic keratoses on penis.
AB - INTRODUCTION: Seborrheic keratoses are very common benign epidermal tumors.
Despite the high frequency, the pathogenesis is still unknown. They are extremely
rare in the genital area. The participation of human papilloma viruses (HPVs) in
pathogenesis of seborrheic keratoses is being discussed. AIMS: The aims of this
case report are to inform about extremely rare lesion in genital area in a young
man and evaluate the association of HPVs in the development of seborrheic
keratoses. METHODS: We used histopathological examination to establish the
correct diagnosis, which revealed signs of seborrheic keratosis. The real-time
polymerase chain reaction method confirmed low-risk HPV 6 from the lesions. MAIN
OUTCOME MEASURES: HPVs may play a role in pathogenesis of seborrheic keratoses.
RESULTS: The patient was successfully treated with shave excision under spinal
anesthesia. Six-month follow-up was without any recurrence. We suggest that HPVs
can be considered as etiologic factor in creation of seborrheic keratosis.
CONCLUSIONS: Seborrheic keratoses are very common on sun-exposed skin, but they
are rare in the genital area, such as on the shaft of penis. This localization
may lead to misdiagnosis. Seborrheic keratoses in genital area might negatively
influence the sexual life of the patient. Containing HPV 6 low-risk virus, they
never lead to malignant transformation.
PMID- 25135109
TI - Regulating drug release from pH- and temperature-responsive electrospun CTS-g
PNIPAAm/poly(ethylene oxide) hydrogel nanofibers.
AB - Temperature- and pH-responsive polymers have been widely investigated as smart
drug release systems. However, dual-sensitive polymers in the form of nanofibers,
which is advantageous in achieving rapid transfer of stimulus to the smart
polymeric structures for regulating drug release behavior, have rarely been
explored. In this study, chitosan-graft-poly(N-isopropylacrylamide) (CTS-g
PNIPAAm) copolymer was synthesized by using 1-ethyl-3-(3
dimethylaminopropyl)carbodiimide (EDC) and N-hydroxy succinimide (NHS) as
grafting agents to graft carboxyl-terminated PNIPAAm (PNIPAAm-COOH) chains onto
the CTS biomacromolecules, and then CTS-g-PNIPAAm with or without bovine serum
albumin (BSA) was fabricated into nanofibers through electrospinning using
poly(ethylene oxide) (PEO, 10 wt%) as a fiber-forming facilitating additive. The
BSA laden CTS-g-PNIPAAm/PEO hydrogel nanofibers were tested to determine their
drug release profiles by varying pH and temperature. Finally, cytotoxicity of the
CTS-g-PNIPAAm/PEO hydrogel nanofibers was evaluated by assaying the L929 cell
proliferation using the MTT method. It was found that the synthesized CTS-g
PNIPAAm possessed a temperature-induced phase transition and lower critical
solution temperature (LCST) at 32 degrees C in aqueous solutions. The rate of
BSA release could be well modulated by altering the environmental pH and
temperature of the hydrogel nanofibers. The CTS-g-PNIPAAm/PEO hydrogel nanofibers
supported L929 cell growth, indicative of appropriate cytocompatibility. Our
current work could pave the way towards developing multi-stimuli responsive
nanofibrous smart materials for potential applications in the fields of drug
delivery and tissue engineering.
PMID- 25135110
TI - Effects of bisoprolol and losartan treatment in the hypertrophic and failing
right heart.
AB - BACKGROUND: Sympathetic adrenergic stimulation and the renin-angiotensin
aldosterone system are highly elevated in right heart failure. We evaluated if
treatment with the adrenergic receptor blocker bisoprolol or the angiotensin II
receptor blocker losartan could prevent the progression of right ventricular (RV)
hypertrophy and failure in rats after pulmonary trunk banding (PTB). METHODS AND
RESULTS: Male Wistar rats were randomized to severe PTB with a 0.5-mm banding
clip (PTB0.5, n = 29), moderate PTB with a 0.6-mm banding clip (PTB0.6, n = 28),
or sham operation (SHAM, n = 13). The PTB0.5 and PTB0.6 rats were randomized to 6
weeks of 10 mg/kg/d bisoprolol treatment, 20 mg/kg/d losartan treatment, or
vehicle treatment. The PTB caused hypertrophy, dilation, and reduced function of
the RV in all rats subjected to the procedure. Rats subjected to the more severe
banding developed decompensated RV failure with extracardiac manifestations.
Treatment with bisoprolol slowed the heart rate, and treatment with losartan
lowered mean arterial pressure, confirming adequate dosing, but none of the
treatments improved RV function or arrested the progression of RV hypertrophy and
failure compared with vehicle. CONCLUSIONS: In our PTB model of pressure overload
induced RV hypertrophy and failure, treatment with bisoprolol and losartan did
not demonstrate any beneficial effects in compensated or decompensated RV
failure.
PMID- 25135111
TI - NF-kappaB repressing factor downregulates basal expression and mycobacterium
tuberculosis induced IP-10 and IL-8 synthesis via interference with NF-kappaB in
monocytes.
AB - BACKGROUND: Our previous study showed NF-kappaB repressing factor (NKRF)
downregulates IP-10 and IL-8 synthesis in the peripheral blood mononuclear cells
and alveolar macrophages of TB patients with high bacterial loads. However, the
mechanism underlying the repressive effect of NKRF is not fully understood.
RESULTS: The levels of IP-10, IL-8 and NKRF were significantly up-regulated in
THP-1 cells treated with heated mycobacterium tuberculosis (H. TB). NKRF
inhibited NF-kappaB-mediated IP-10 and IL-8 synthesis and release induced by H.
TB. The repressive effect of NKRF is mediated via interference with NF-kappaB
(p65) binding and RNA polymerase II recruitment to promoter sites of IP-10 and IL
8. CONCLUSIONS: We have elucidated that direct contact with MTb induces IP-10, IL
8 and a concomitant increase in NKRF in THP-1 cells. The up-regulated NKRF serves
as an endogenous repressor for IP-10 and IL-8 synthesis to hinder host from
robust response to MTb infection.
PMID- 25135112
TI - Assessment of type 2 diabetes risk conferred by SNPs rs2241766 and rs1501299 in
the ADIPOQ gene, a case/control study combined with meta-analyses.
AB - We conducted a case/control study to assess the impact of two SNPs, rs2241766 and
rs1501299 within the ADIPOQ gene, on type 2 diabetes (T2D) susceptibility in a
Chinese Han dataset (741 cases and 902 controls). SNP rs2241766 was found
significantly associated with T2D risk in the additive model, dominant model and
recessive model. A marginal association was detected for SNP rs1501299 in the
additive model and recessive model after Bonferroni correction, and haplotype
analysis provided additional evidence supporting the association between these
two SNPs and T2D risk. A meta-analysis including 29 published datasets along with
current dataset was next carried out to further confirm the association. In
consistent with our case/control results, rs2241766 showed a significant
association with T2D in the dominant model and additive model, and the
association between rs1501299 and T2D was also characterized in the homozygote
model, dominant model, recessive model, and additive model. Of note, the
association became much stronger in East Asians after exclusion of ethnic
stratification. Together, our data support that the rs2241766 and rs1501299
polymorphisms within the ADIPOQ gene confer genetic susceptibility for type 2
diabetes, especially in the Chinese Han population.
PMID- 25135114
TI - Munchausen syndrome: multiple episodes of polymicrobial bacteremia.
PMID- 25135113
TI - Optical mapping of optogenetically shaped cardiac action potentials.
AB - Light-mediated silencing and stimulation of cardiac excitability, an important
complement to electrical stimulation, promises important discoveries and
therapies. To date, cardiac optogenetics has been studied with patch-clamp,
multielectrode arrays, video microscopy, and an all-optical system measuring
calcium transients. The future lies in achieving simultaneous optical acquisition
of excitability signals and optogenetic control, both with high spatio-temporal
resolution. Here, we make progress by combining optical mapping of action
potentials with concurrent activation of channelrhodopsin-2 (ChR2) or
halorhodopsin (eNpHR3.0), via an all-optical system applied to monolayers of
neonatal rat ventricular myocytes (NRVM). Additionally, we explore the capability
of ChR2 and eNpHR3.0 to shape action-potential waveforms, potentially aiding the
study of short/long QT syndromes that result from abnormal changes in action
potential duration (APD). These results show the promise of an all-optical system
to acquire action potentials with precise temporal optogenetics control,
achieving a long-sought flexibility beyond the means of conventional electrical
stimulation.
PMID- 25135115
TI - Serotonergic systems are implicated in antinociceptive effect of m
trifluoromethyl diphenyl diselenide in the mouse glutamate test.
AB - The organoselenium compound m-trifluoromethyl diphenyl diselenide (m-CF3-PhSe)2
has antinociceptive actions in several animal models, which are mediated by
interaction with endogenous opioid systems. It also shows antidepressant-like
action mediated by both opioid and serotonergic systems. Considering that
serotonin (5-HT) plays an important role in the descending control of pain, this
study further investigated the role of serotonergic systems in the
antinociceptive action of (m-CF3-PhSe)2 in the glutamate-induced licking behavior
model in mice. (m-CF3-PhSe)2 (1-50 mg/kg, p.o.), morphine (2.5 mg/kg, s.c.) or
paroxetine (5 mg/kg, i.p.) reduced glutamate-induced nociception. Selective 5
HT1A and 5-HT2A receptor antagonists, WAY100635 (0.7 mg/kg, i.p.) and ketanserin
(0.3 mg/kg, i.p.), but not the selective 5-HT3 receptor antagonist, ondansetron
(0.5 mg/kg, i.p.), prevented the antinociceptive effect of (m-CF3-PhSe)2 (10
mg/kg) in the glutamate test. In biochemical studies, (m-CF3-PhSe)2 (10 and 50
mg/kg) decreased [(3)H]5-HT uptake in crude synaptosomes of mouse brains and
slightly inhibited in vitro [(3)H]5-HT binding. In kinetic studies, the selenium
(Se) distribution was determined at different time points after the
administration of (m-CF3-PhSe)2 (500 mg/kg, p.o.) to mice. After 30 min, a high
amount of Se was found in liver and kidneys, followed by the lung, red blood
cells, serum and brain. A significant amount of Se accumulated in fat over the
course of 8h. Urine was an important route of Se excretion originating from (m
CF3-PhSe)2. Collectively, results of this study indicate an involvement of the
serotonergic systems in the antinociceptive effect of (m-CF3-PhSe)2 and a wide
distribution of Se derived from this compound.
PMID- 25135117
TI - Interventional cardiology: SORTing OUT stents--everolimus limits very late stent
thrombosis.
PMID- 25135116
TI - Plant disease resistance is augmented in uzu barley lines modified in the
brassinosteroid receptor BRI1.
AB - BACKGROUND: Brassinosteroid hormones regulate many aspects of plant growth and
development. The membrane receptor BRI1 is a central player in the
brassinosteroid signaling cascade. Semi-dwarf 'uzu' barley carries a mutation in
a conserved domain of the kinase tail of BRI1 and this mutant allele is
recognised for its positive contribution to both yield and lodging resistance.
RESULTS: Here we show that uzu barley exhibits enhanced resistance to a range of
pathogens. It was due to a combination of preformed, inducible and constitutive
defence responses, as determined by a combination of transcriptomic and
biochemical studies. Gene expression studies were used to determine that the uzu
derivatives are attenuated in downstream brassinosteroid signaling. The reduction
of BRI1 RNA levels via virus-induced gene silencing compromised uzu disease
resistance. CONCLUSIONS: The pathogen resistance of uzu derivatives may be due to
pleiotropic effects of BRI1 or the cascade effects of their repressed BR
signaling.
PMID- 25135118
TI - Coronary artery disease: Cost-effectiveness of CABG surgery versus PCI in complex
CAD.
PMID- 25135119
TI - Diabetes: Effects of strict glycaemic control on ischaemic heart disease.
PMID- 25135121
TI - Treatment patterns and their outcomes of acute aortic intramural hematoma in real
world: multicenter registry for aortic intramural hematoma.
AB - BACKGROUND: Intramural hematoma of the aorta (IMH), a variant of classic aortic
dissection, shows very dynamic process in the early phase. The aim of this study
is to evaluate clinical outcomes of patients with acute aortic IMH from real
world registry data. METHODS: We analyzed 165 consecutive patients with acute IMH
from five medical centers in Korea. All patients were divided into two groups;
type A (n = 61, 37.0%) and type B (n = 104, 63.0%) according to the Stanford
classification. Clinical outcomes and morphological evolution by CT were analyzed
for 2 years. RESULTS: Most of the patients (77.0% of type A and 99.0% of type B,
P < 0.001) were treated medically during their initial hospitalization. There
were no significant differences in in-hospital mortality (4.9% vs. 2.9%, P =
0.671) and 2-year mortality (13.1% vs. 11.5%, P = 0.765) between two groups.
During the 2-year follow up period, progression to aortic dissection (18.0% vs.
6.7%, P = 0.037) and surgical treatment (29.5% vs. 2.9%, P < 0.001) were higher
in type A. For the type A patients, there were no significant difference in in
hospital mortality (7.1% of surgery vs. 4.3% of medical, P = 0.428) and 2-year
mortality (7.1% of surgery vs. 14.9% of medical, P = 0.450) in terms of initial
treatment strategy. CONCLUSION: For real world practice in Korea, most of IMH
patients were treated medically at presentation and showed favorable outcomes.
Thus, even in type A acute IMH, early medical treatment with alternative surgical
conversion for selected, complicated cases would be a favorable treatment option.
PMID- 25135122
TI - Obesity delays functional recovery in trauma patients.
AB - BACKGROUND: Obesity is known to complicate trauma hospital stays. We hypothesize
that obesity delays functional recovery in trauma patients. MATERIALS AND
METHODS: Between 2005 and 2007, adult patients with a hospital length of stay >24
h were prospectively recruited for the study. Functional Independence Measurement
(FIM) scores were calculated at the time of admission, discharge, and 6 mo after
discharge. Patients were classified as nonobese (body mass index [BMI] <25),
overweight (BMI >=25 and <30), obese (BMI >=30 and <35), and morbidly obese (BMI
>=35). Multivariate analyses were performed to determine the impact of obesity on
FIM scores. RESULTS: Two hundred thirty-five patients met the study inclusion
criteria. Average injury severity scores was >18. We recorded no mortality at the
time of discharge and follow-up. During acute hospital stay stage, nonobese
patients had an average of 24 points increase on FIM scores compared with
morbidly obese patients with 16 points improvement (P = 0.023). Compared with
nonobese patients, the rate of recovery was reduced by 30% in overweight (P =
0.034), 37% in obese (P = 0.025), and 48% in morbidly obese patients (P = 0.003).
Alternatively, we found that for every unit increase in BMI, the functional
recovery rate was reduced by 4% (P < 0.001). Changes in FIM scores during the
postdischarge period were not significantly different by obesity classification,
and all groups achieve similar functional outcome at follow-up (P = 0.482).
CONCLUSIONS: Most trauma patients achieve full functional recovery some time
after hospital discharge, but the recovery is delayed in obese patients and the
delay is directly correlated with the severity of obesity.
PMID- 25135120
TI - Clinicopathological characteristics of oral squamous cell carcinoma in Northern
Norway: a retrospective study.
AB - BACKGROUND: The main aim of the study was to evaluate if patients with oral
squamous carcinomas in Northern Norway differ from patients in other countries
with regard to clinicopathological characteristics and also study the influence
of risk factors. Such a comparison is of demographical interest, and also
important for the interpretation of result from studies on prognostic biomarkers.
METHODS: We describe clinicopathological characteristics of 133 North Norwegian
patients diagnosed with squamous cell carcinoma of the oral cavity in the period
1986-2002, and evaluate the significance of different risk factors. RESULTS: The
cohort consisted of 69 men and 64 women, giving male/female ratio of 1.1. Forty
seven of the 133 patients (35%) died of the disease within 5 years from
diagnosis. There was no significant difference between the genders concerning
time to disease specific death, even though men both smoked and drank more
alcohol than women. As expected, the strongest predictors for disease specific
death were tumour size and the presence of regional lymph node metastasis. We
also found that heavy smokers and drinkers presented with more advanced disease,
more often localized to the floor of mouth compared to non-smoking and abstinent
patients, who more often presented with tumours of the mobile tongue.
CONCLUSIONS: Our results correlate well with previously published
clinicopathological data on comparable cohorts, which is important when
considering the applicability of results from biomarker studies performed on this
material compared to other cohorts, and vice versa.
PMID- 25135123
TI - Metformin improves skin flap survival through nitric oxide system.
AB - BACKGROUND: Metformin has shown cardioprotective effects in experimental models
of ischemia reperfusion, which is partially mediated through nitric oxide (NO)
synthesis. We investigated the effects of metformin pretreatment in a rat model
of random-pattern skin flap, and the probable role of NO system. MATERIALS AND
METHODS: In the first experiment, the rats received increasing doses of metformin
(150, 200, and 300 mg/kg), 4 h before the procedure. Dorsal skin flaps with
caudal pedicles were elevated at the midline and flap survival was measured 7 d
after surgery. Pathologic review of the skin flap specimen was performed in a
subset of animals. In the second experiment, for evaluation of the role of NO, an
NO synthase inhibitor N-nitro-L-arginine methyl ester hydrochloride (L-NAME) was
administered with and without the effective dose of metformin. In the next
experiment, subtherapeutic dose of NO precursor, L-Arginine, was administered
with and without subeffective dose of metformin. RESULTS: Metformin pretreatment
at doses of 200 and 300 mg/kg significantly increased skin flap survival rate.
However, administration of L-NAME abolished the protective effects of metformin.
On the other hand, subtherapeutic dose of L-arginine augmented the effects of low
dose metformin and significantly increased skin flap survival. Skin flaps from
those rats that received 300 mg/kg metformin pretreatment and those treated with
subtherapeutic doses of L-arginine and metformin showed increased vasodilation
compared with control group. CONCLUSIONS: Metformin pretreatment can improve skin
flap survival through an NO dependent pathway.
PMID- 25135126
TI - Electrocardiographic screening should not be implemented for children and
adolescents between ages 1 and 19 in the United States.
PMID- 25135125
TI - Electrocardiographic screening of all infants, children, and teenagers should be
performed.
PMID- 25135124
TI - Impact of oral melatonin on critically ill adult patients with ICU sleep
deprivation: study protocol for a randomized controlled trial.
AB - BACKGROUND: Sleep deprivation is common in critically ill patients in intensive
care units (ICU). It can result in delirium, difficulty weaning, repeated
nosocomial infections, prolonged ICU length of stay and increased ICU mortality.
Melatonin, a physiological sleep regulator, is well known to benefit sleep
quality in certain people, but evidence for the effectiveness in ICU sleep
disturbance is limited. METHODS/DESIGN: This study has a prospective, randomized,
double-blind, controlled, parallel-group design. Eligible patients are randomly
assigned to one of the two treatment study groups, labelled the 'melatonin group'
or the 'placebo group'. A dose of 3 mg of oral melatonin or placebo is
administered at 9:00 pm on four consecutive days. Earplugs and eye masks are made
available to every participant. We plan to enrol 198 patients. The primary
outcome is the objective sleep quality measured by the 24-hour polysomnography.
The secondary outcomes are the subjective sleep quality assessed by the Richards
Campbell Sleep Questionnaire, the anxiety level evaluated by the Visual Analogue
Scale-Anxiety, the number of delirium-free days in 8 and 28 days, the number of
ventilation-free days in 28 days, the number of antibiotic-free days, ICU length
of stay, the overall ICU mortality in 28 days and the incidence and severity of
the side effects of melatonin in ICU patients. Additionally, the body stress
levels, oxidative stress levels and inflammation levels are obtained via
measuring the plasma melatonin, cortisone, norepinephrine, malonaldehyde(MDA),
superoxide dismutase(SOD), interleukin-6 (IL-6) and interleukin-8 (IL
8)concentrations. DISCUSSION: The proposed study will be the first randomized
controlled study to use the polysomnography, which is the gold standard of
assessing sleep quality, to evaluate the effect of melatonin on the sleep quality
and circadian rhythms of ICU patients. The results may recommend a new treatment
for ICU patients with sleep deprivation that is safe, effective and easily
implementable in daily practice. TRIAL REGISTRATION: This study was registered
with ClinicalTrials (NCT; registration number: ChiCTR-TRC-14004319) on 4 March
2013.
PMID- 25135127
TI - Cardiovascular implications in preeclampsia: an overview.
PMID- 25135130
TI - Demonstration of inverted left atrial appendage using cardiac computed
tomography: an unusual complication mimicking left atrial mass after cardiac
surgery.
PMID- 25135129
TI - Impact of septal radiofrequency ventricular tachycardia ablation: insights from
magnetic resonance imaging.
PMID- 25135131
TI - Cerebral and sinus vein thrombosis.
PMID- 25135132
TI - Letter by Li and Yu regarding article, "ten-eleven translocation-2 (TET2) is a
master regulator of smooth muscle cell plasticity".
PMID- 25135133
TI - Response to letter regarding article, "ten-eleven translocation-2 (TET2) is a
master regulator of smooth muscle cell plasticity".
PMID- 25135134
TI - Letter by Zhang regarding article, "early dual versus mono antiplatelet therapy
for acute non-cardioembolic ischemic stroke or transient ischemic attack: an
updated systematic review and meta-analysis".
PMID- 25135135
TI - Response to letter regarding article, "early dual versus mono antiplatelet
therapy for acute non-cardioembolic ischemic stroke or transient ischemic attack:
an updated systematic review and meta-analysis".
PMID- 25135137
TI - [Occurrence of Shiga toxigenic Escherichia coli strains in pigs and cattle at
slaughterhouses in the Czech Republic in 2013].
AB - OBJECTIVES: This study was performed in cooperation with the State Veterinary
Administration (SVA) in order to monitor the occurrence of Shiga toxin-producing
Escherichia coli isolates in swabs from the carcasses of pigs and cattle at
slaughterhouses. MATERIAL AND METHODS: From June to August 2013, SVA staff took
168 swabs from cattle and 318 from pigs at 157 different slaughters in the Czech
Republic. Basic processing of the samples was carried out in the State Veterinary
Institutes (SVIs) in Prague, Jihlava and Olomouc according to the methodical
process coordinated by the National reference laboratory (NRL) for Escherichia
coli (Czech Ministry of Agriculture). The procedure was based on the guideline
ISO TS 13136. RESULTS: Out of the 486 swabs, twenty-two positive samples were
detected. There were a total of 22 isolates of Shiga toxigenic E. coli (STEC) and
1 strain with the characteristic of enterohemorrhagic E. coli (EHEC). Genes
typical for enteroaggregative E. coli (EAggEC) were not found in any of the
isolates. Most STEC strains originated from pigs. The stx1 gene was detected
twice (stx1a, stx1d) and the stx2 gene 13 times (12 times stx2e, once stx2a).
Seven STEC isolates were detected from samples of cattle origin. One strain was
stx1 (stx1a) -positive, the stx2 gene was found 6 times (4 stx2e, 1 stx2a and 1
stx2c). One isolate carried simultaneously both stx1a and stx2a. Each of the
serogroups O91, O113 and O146 described as etiological agents of severe disease
in humans were detected only once. None of these strains harbored additional
virulence factors typical for strains causing serious illness. CONCLUSION:
RESULTS of this study show the overall prevalence of Shiga toxigenic E. coli of
4.5 % and 0.2 % of enterohemorrhagic strains in the studied samples. Raw meat
originating from local farms does not currently represent an important source of
STEC for humans.
PMID- 25135138
TI - [Familial occurrence of botulism - a case report].
AB - Botulism, a life-threatening condition, is very rare in the Czech Republic. Since
1960, a total of 155 cases have been reported; between 2010 and 2012, not a
single case was identified. This is a case report of familiar occurrence of
botulism following consumption of home-made pork and liver pate in three family
members admitted to the Department of Infectious, Tropical and Parasitic
Diseases, Na Bulovce Hospital in Prague in May 2013. The neurological symptoms
were dominated by diplopia and dysarthria. After administration of an antitoxin,
all patients recovered. Given the poor availability of the antitoxin, a decision
was made following this small family epidemic to have an emergency reserve of
life-saving anti-infective drugs for the Czech Republic in the Toxicological
Information Center in Prague.
PMID- 25135139
TI - [Emergency reserve of life-saving anti-infective drugs].
AB - OBJECTIVES: Problems with importing non-registered medicines for treating rare
life-threatening infectious diseases led to establishment of the Emergency Anti
Infective Drug Reserve (EAIDR) for the Czech Republic. METHODS: Thirteen anti
infective drugs are included in the project: antisera against rabies virus,
varicella-zoster virus, and botulinum toxin; antituberculosis drugs (intravenous
rifampicin and isoniazid; capreomycin, cycloserine, and clofazimine);
antiparasitics (intravenous quinine, primaquine, meglumine antimoniate, and
praziquantel); and pentamidine. These drugs are imported according to the Czech
drug legislation (specific drug availability programs). Realization: The project,
approved by the Czech Ministry of Health in September 2013, was started in
January 2014. The anti-infective drugs sufficient for 2-4 patients are
permanently available in the Toxicological Information Center (TIC) in Prague.
The medicines can be applied in any hospital throughout the Czech Republic within
several hours. CONCLUSIONS: All but three drugs are available at present; the
remaining ones will be imported after new batches of these drugs are released.
PMID- 25135140
TI - [Campylobacteriosis].
AB - Campylobacteriosis belongs to the most frequent bacterial gastrointestinal
infections worldwide. In the past several years, an increasing trend in the
prevalence of campylobacteriosis has been observed in many countries. The rapid
spread of antibiotic resistance in Campylobacter spp. also poses a major
challenge. The authors review current knowledge on the microbiology of
Campylobacter spp., complex pathogenetic as well as pathophysiological mechanisms
in the development and course of campylobacteriosis and related complications
such as Guillain-Barre syndrome.
PMID- 25135141
TI - [Diagnosis and therapy of Clostridium difficile infection: Czech national
guidelines].
AB - Clostridium difficile infection (CDI) is a disease of varying severity. Its
manifestations range from mild diarrhea to life-threatening paralytic ileus,
painful distension of the large bowel, and sepsis. Another possible manifestation
of the disease is recurring colitis that can exhaust the patient. For
establishing the diagnosis, the patient's stool should be examined with two or
three different microbiological methods (testing for clostridial toxins A and B;
testing for clostridial glutamate dehydrogenase, anaerobic culture with specific
media, or PCR detection of genes for production of clostridial toxins). An
alternative way of assessing the etiology is colonoscopic examination; the
disease is confirmed if characteristic patchy pseudomembranes are present in the
bowel mucosa. Optimal treatment depends on severity of the disease and on the
risk of recurrence. Metronidazole, vancomycin and fidaxomicin are used as basic
drugs. Fecal transplantation is effective in recurrent disease. In the hospital
setting, patients suffering from CDI should be isolated for the entire duration
of diarrhea. Surveillance rules also should be applied, together with early
treatment of symptomatic patients and prevention of the spread of the infection.
Higher incidence of CDI in a ward implies that the local antibiotic prescription
habits should be revised.
PMID- 25135142
TI - Response to: laboratory assessment may be dependent on the time of liver biopsy.
PMID- 25135144
TI - [Critical care medicine and transplantation medicine: A task for each intensive
care unit].
PMID- 25135143
TI - Exploration of shared decision-making processes among dieticians and patients
during a consultation for the nutritional treatment of dyslipidaemia.
AB - BACKGROUND: Shared decision making (SDM) holds great potential for improving the
therapeutic efficiency and quality of nutritional treatment of dyslipidaemia by
promoting patient involvement in decision making. Adoption of specific behaviours
fostering SDM during consultations has yet to be studied in routine dietetic
practice. OBJECTIVE: Using a cross-sectional study design, we aimed to explore
both dieticians' and patients' adoption of SDM behaviours in dietetic
consultations regarding the nutritional treatment of dyslipidaemia. METHODS:
Twenty-six dieticians working in local health clinics in the Quebec City
metropolitan area were each asked to identify one dyslipidaemic patient they
would see in an upcoming consultation. Based on the Theory of Planned Behaviour
(TPB), questionnaires were designed to study two targeted SDM behaviours: 'to
discuss nutritional treatment options for dyslipidaemia' and 'to discuss
patients' values and preferences about nutritional treatment options for
dyslipidaemia'. These questionnaires were administered to the dietician-patient
dyad individually before the consultation. Associations between TPB constructs
(attitude, subjective norm and perceived behavioural control) towards behavioural
intentions were analysed using Spearman's partial correlations. RESULTS: Thirteen
unique patient-dietician dyads completed the study. Perceived behavioural control
was the only TPB construct significantly associated with both dieticians' and
patients' intentions to adopt the targeted SDM behaviours (P < 0.05).
CONCLUSIONS: As perceived behavioural control seems to determine dieticians' and
patients' adoption of SDM behaviours, interventions addressing barriers and
reinforcing enablers of these behaviours are indicated. This exploratory study
highlights issues that could be addressed in future research endeavours to expand
the knowledge base relating to SDM adoption in dietetic practice.
PMID- 25135145
TI - Fosterage as a system of dispersed cooperative breeding: evidence from the Himba.
AB - Humans are obligate cooperative breeders, relying heavily on support from kin to
raise children. To date, most studies of cooperative breeding have focused on
help that supplements rather than replaces parental care. Here we propose that
fosterage can act as a form of dispersed cooperative breeding, one that enhances
women's fitness by allowing them to disinvest in some children and reallocate
effort to others. We test this hypothesis through a series of predictions about
the costs and benefits of fosterage for mothers, foster parents, and foster
children using data from the Himba, a group of Namibian agro-pastoralists. We
show that fostering out children enhances mothers' fitness, and we provide
evidence for a causal link from fosterage to enhanced fitness by showing that
fosterage of early-born children is associated with greater maternal reproductive
success. Foster parents minimize the costs of fosterage by skewing their care
toward their postreproductive years, and by mainly fostering close kin. However,
the system is associated with some detrimental effects on foster children, who
are more likely to be stunted and underweight than their non-fostered
counterparts.
PMID- 25135146
TI - The physiologic effects of pain on the endocrine system.
AB - Severe pain has profound physiologic effects on the endocrine system. Serum
hormone abnormalities may result and these serve as biomarkers for the presence
of severe pain and the need to replace hormones to achieve pain control.
Initially severe pain causes a hyperarousal of the hypothalamic-pituitary-adrenal
system which results in elevated serum hormone levels such as
adrenocorticotropin, cortisol, and pregnenolone. If the severe pain does not
abate, however, the system cannot maintain its normal hormone production and
serum levels of some hormones may drop below normal range. Some hormones are so
critical to pain control that a deficiency may enhance pain and retard healing.
PMID- 25135148
TI - Knowledge about Pain Clinics and Pain Physician among General Practitioners: A
Cross-sectional Survey.
AB - INTRODUCTION: There is an on-going debate about what qualifies one to be called a
"pain physician" and who can run the "pain clinic". Currently, the discipline of
anesthesiology is producing the majority of pain physicians. A literature search
was unable to find data for any Pakistani or other South Asian countries with
regards to general practitioner (GP) knowledge about pain clinics and pain
physicians. The main objective of this study was to assess the awareness of GPs
regarding the existence of the pain clinic and pain physician. METHODS: A total
of 411 GPs were included in this cross-sectional survey. A questionnaire
consisting of ten questions was designed to identify their knowledge about the
existence of pain clinics and pain physicians. Questionnaires were completed in
the field and edited for the inconsistencies and in-completeness. RESULTS: The
results showed that only 52.6% of GPs were aware of the existence of pain
clinics. The survey showed that 37.5% believe neurologists are the pain
physicians and only 10.9% know that pain clinics are run by anesthesiologist. The
vast majority (85.0%) are unaware of the modern pain relieving methods used in
pain clinics. CONCLUSION: The survey indicates that nearly half of the GPs are
unaware of the existence of pain clinics and pain physicians, and the majority of
GPs are unaware of new pain relieving methods.
PMID- 25135149
TI - Pain intensity and its association with negative mood States in patients with
spinal cord injury.
AB - INTRODUCTION: Chronic and persistent pain is a prevalent and debilitating
secondary condition in patients with a neurological injury such as spinal cord
injury (SCI). Patients with SCI have an increased risk of developing other co
morbid conditions such as elevated negative mood states. Arguably, the presence
of chronic pain would act to intensify the chances of developing negative mood
states as opposed to resilient mental states. The objective of this research was
to investigate the association between pain intensity and levels of negative mood
states in adult patients with SCI. METHODS: Participants included 107 adults with
SCI living in the community who completed an assessment regimen in a relaxed
environment. Mean pain intensity over a period of 1 week and the Profile of Mood
States, a validated psychometric measure of mood states (anxiety, depressed mood,
anger, vigor, fatigue, confusion and total negative mood score) were used to
determine associations between pain intensity and mood states. The sample was
divided into a low pain intensity sub-group (<4 where 0 = no pain; 10 = worst
pain imaginable) and a clinically significant or high pain intensity sub-group
(>=4), allowing negative mood to be compared between the sub-groups. RESULTS:
Mean age was 47.1 years, and 87% of the sample was male. Clinically significant
pain intensity over the week prior to assessment was found in 52% of the 107
participants. The high pain intensity sub-group was found to have significantly
elevated anxiety, depressed mood, anger, fatigue, confusion and significantly
reduced vigor. CONCLUSION: These results provide further evidence that patients
with SCI experience clinically elevated negative mood states if they have intense
levels of pain over extended periods of time. In contrast, patients without
intense pain have mood states similar to those in the able-bodied community.
Implications for the treatment of SCI are discussed.
PMID- 25135150
TI - An evaluation of total disintegration time for three different doses of
sublingual fentanyl tablets in patients with breakthrough pain.
AB - INTRODUCTION: Breakthrough pain is common among patients with cancer and presents
challenges to effective pain management. Breakthrough pain is characterized by
rapid onset, severe intensity, and duration typically lasting <1 h. Thus, optimal
relief from breakthrough pain is best attained by administering analgesics with
dissolution times and bioavailabilities that closely match the onset and duration
of breakthrough pain. The objective of this study was to assess complete
disintegration time of three different doses of sublingual fentanyl tablets in
opioid-tolerant patients. METHODS: This was a single-center, non-randomized, open
label study. Opioid-tolerant adult patients (N = 30) with chronic pain were
assigned to one of three dose groups and self-administered a single 100, 200, or
300 MUg sublingual fentanyl tablet (Abstral((r)), Galena Biopharma, Portland, OR,
USA). Time to complete disintegration was measured by each patient with a
stopwatch and independently verified by study personnel. RESULTS: Disintegration
time (mean +/- SD) for sublingual fentanyl tablets (all doses) was 88.2 +/- 55.1
s. Mean disintegration times tended to be slightly longer for the 200 MUg (96.7
+/- 57.9 s) and 300 MUg doses (98.6 +/- 64.8 s) compared to the 100 MUg dose
(69.5 +/- 40.5 s). Differences were not statistically significant. Disintegration
time was not significantly different between men and women and was not affected
by age. CONCLUSION: Sublingual fentanyl tablets dissolved rapidly (average time
<2 min) in all patients, with the higher doses taking slightly more time to
dissolve.
PMID- 25135147
TI - Management of fibromyalgia syndrome: review of evidence.
AB - Fibromyalgia syndrome (FMS) is a common chronic musculoskeletal pain disorder of
unknown etiology and characterized by generalized body pain, hyperalgesia, and
other functional and emotional comorbidities. Despite extensive research, no
treatment modality is effective for all FMS patients. In this paper, we briefly
review the history of FMS and diagnostic criteria, and potential
pathophysiological mechanisms including central pain modulation,
neurotransmitters, sympatho-adrenal and hypothalamic-pituitary-adrenal systems
and peripheral muscle issues. The primary focus of the paper is to review
treatment options for managing fibromyalgia symptoms. We will discuss FDA
approved medications and other pharmacologic agents, and non-pharmacologic
treatments that have shown promising effects.
PMID- 25135151
TI - Complex regional pain syndrome treated with intravenous immunoglobulin in a
patient with common variable immune deficiency.
AB - INTRODUCTION: Common variable immunodeficiency (CVID) represents a large
heterogeneous group of antibody-deficiency syndromes associated with a wide range
of clinical features and a lack of defined causes in the realm of primary
immunodeficiencies. Here, we present a case of CVID in a 62-year-old white male
patient with a history of longstanding complex regional pain syndrome (CRPS).
CASE PRESENTATION: His medical history included multiple sinus infections per
year and several pneumonias requiring antibiotics. He has had various back
surgeries, including a laminectomy at the L4 level 1 year prior to his diagnosis.
Thereafter, he underwent four sympathetic nerve blocks with minimal pain relief.
Blood chemistries showed a normal white blood cell count with a normal
differential, but increased erythrocyte sedimentation rate and C-reactive protein
levels. Total Ig (Immunoglobulin)G was 611 mg/dL (normal 700-1,600), IgG1 was 425
mg/dL (341-894), IgG2 was 114 mg/dL (171-632), IgG3 was 14.4 mg/dL (18.4-106),
and IgG4 was 7.4 mg/dL (2.4-121). IgA was 47 mg/dL (normal 70-400), IgM was 131
mg/dL (40-230), and IgE was 4.5 kU/L (<4.0). He only had 10 of 23 pneumococcal
titers in the protective range post-vaccination. Upon treatment of the CVID with
intravenous immunoglobulin, the patient's pain levels were significantly
decreased and have been maintained for more than 2 years. CONCLUSION: Therefore,
immunoglobulin therapy appears to have been beneficial in the treatment of the
patient's symptoms of CRPS, including pain. Additional studies investigating the
mechanism by which immunoglobulin therapy may reduce the inflammation and pain of
CRPS are needed.
PMID- 25135152
TI - Erratum to: Effects of a Single Session Group Intervention for Pain Management in
Chronic Pain Patients: A Pilot Study.
PMID- 25135153
TI - Cryptococcosis-related deaths and associated medical conditions in the United
States, 2000-2010.
AB - Cryptococcosis is an invasive mycotic infection primarily affecting
immunocompromised individuals. The objective of this study was to describe
cryptococcosis mortality and associated medical conditions in the US for the
period 2000-2010. Cryptococcosis-related deaths were identified from the national
multiple-cause-of-death dataset. Mortality trends and comparison analyses were
performed on overall cases of cryptococcosis and by subset [i.e. clinical
manifestations of disease and human immunodeficiency virus (HIV) status]. A
matched case-control analysis was also conducted to describe the associations
between this disease and comorbid medical conditions. A total of 3210
cryptococcosis-related deaths were identified. Cerebral cryptococcosis was the
most commonly reported clinical manifestation of the disease. Approximately one
fifth of the decedents (n = 616) had a co-diagnosis of HIV. Mortality rates were
highest among men, blacks, Hispanics, Native Americans and older adults. Poisson
regression analysis indicated a 6.52% annual decrease in mortality rates for the
study period. HIV (MOR = 35.55, 95% CI 27.95-45.22) and leukaemia (MOR = 16.10,
95% CI 11.24-23.06) were highly associated with cryptococcosis-related deaths.
Cryptococcosis mortality declined significantly during 2000-2010. However, the
disease continues to cause appreciable mortality in the US. With the majority of
decedents having no HIV co-diagnosis, there is still much to be learned about the
epidemiology of this mycosis.
PMID- 25135154
TI - Identifying sources of emerging organic contaminants in a mixed use watershed
using principal components analysis.
AB - Principal components analysis (PCA) was used to identify sources of emerging
organic contaminants in the Zumbro River watershed in Southeastern Minnesota. Two
main principal components (PCs) were identified, which together explained more
than 50% of the variance in the data. Principal Component 1 (PC1) was attributed
to urban wastewater-derived sources, including municipal wastewater and
residential septic tank effluents, while Principal Component 2 (PC2) was
attributed to agricultural sources. The variances of the concentrations of
cotinine, DEET and the prescription drugs carbamazepine, erythromycin and
sulfamethoxazole were best explained by PC1, while the variances of the
concentrations of the agricultural pesticides atrazine, metolachlor and
acetochlor were best explained by PC2. Mixed use compounds carbaryl, iprodione
and daidzein did not specifically group with either PC1 or PC2. Furthermore,
despite the fact that caffeine and acetaminophen have been historically
associated with human use, they could not be attributed to a single dominant land
use category (e.g., urban/residential or agricultural). Contributions from septic
systems did not clarify the source for these two compounds, suggesting that
additional sources, such as runoff from biosolid-amended soils, may exist. Based
on these results, PCA may be a useful way to broadly categorize the sources of
new and previously uncharacterized emerging contaminants or may help to clarify
transport pathways in a given area. Acetaminophen and caffeine were not ideal
markers for urban/residential contamination sources in the study area and may
need to be reconsidered as such in other areas as well.
PMID- 25135155
TI - Letter from the editor.
PMID- 25135157
TI - Comparison of circumferential pulmonary vein isolation and antiarrhythmic drug
therapy in patients with atrial fibrillation.
AB - INTRODUCTION: The aim of this study was to evaluate quality of life after
circumferential pulmonary vein isolation (CPVI) compared with antiarrhythmic drug
therapy (ADT) in treating atrial fibrillation (AF). CPVI is now a common therapy
in AF, but few studies have focused on the effect of CPVI on quality of life.
METHODS: A total of 123 AF patients were followed prospectively. Quality of life
was evaluated comparing CPVI with ADT as a second-line treatment for patients
with AF. The Medical Outcomes Study Short Form (SF)-36 health surveys were
conducted to establish a baseline score before initiation and again at 6 months
after the intervention. RESULTS: Mean follow-up duration was 12.7 +/- 4.3 months.
Of 123 patients enrolled, 66 were randomized to receive CPVI and 57 to ADT alone.
At the 6-month follow-up, 13 (22.8%) patients in the ADT group and 41 (62.1%)
patients in the CPVI group had no recurrence of AF. The SF-36 scales were
significantly higher in the CPVI than in the ADT group, as were the physical
component summary scores (269.3 +/- 58.6 vs. 234.9 +/- 66.9) and mental component
summary scores (273.6 +/- 69.4 vs. 234.1 +/- 44.7). Quality of life was
significantly higher in the CPVI group (except for body pain). CONCLUSION: In
patients with AF, CPVI has superiority over ADT with regards to the maintenance
of sinus rhythm and improvements in quality of life.
PMID- 25135156
TI - Effect of thermal therapy using hot water bottles on brain natriuretic Peptide in
chronic hemodialysis patients.
AB - INTRODUCTION: The use of repeated thermal therapy for improving the symptoms of
chronic heart failure (CHF) has been recently demonstrated. Usually, thermal
therapy requires an infrared dry sauna. However, it is difficult for small
clinics to acquire such an expensive and extensive system. The present study
assessed the efficacy of its substitution with hot water bottles. Moreover, there
are no prior studies demonstrating the efficacy of thermal therapy in
hemodialysis patients with CHF. METHODS: Plasma brain natriuretic peptide (BNP)
levels were evaluated in 98 hemodialysis patients in a clinic. Nine patients
whose BNP levels were >500 pg/mL agreed to be enrolled in the study and received
thermal therapy using hot water bottles. RESULTS: Plasma BNP levels, a potential
marker for CHF, tended to decrease (891 +/- 448 to 680 +/- 339 pg/mL), but the
difference was not significant (P = 0.0845). The oral temperature changed from
36.44 +/- 0.45 degrees C to 37.04 +/- 0.48 degrees C (+0.597 degrees C, P <
0.0001). No side effects were experienced during the therapy. Moreover, most
patients had an improvement in their symptoms and the ability to perform
activities of daily living. CONCLUSION: Thermal therapy using hot water bottles
is very safe and tends to reduce plasma BNP levels in hemodialysis patients with
CHF.
PMID- 25135158
TI - Lercanidipine effect on polymorphonuclear leukocyte-related inflammation and
insulin resistance in essential hypertension patients.
AB - INTRODUCTION: Inflammation, insulin resistance, and oxidative stress (OS) are
among the mechanisms that have been implicated in the pathogenesis of essential
hypertension (EH). Peripheral polymorphonuclear leukocytes (PMNLs) are primed in
EH patients, releasing uncontrolled superoxide anions contributing to OS in these
patients. PMNL priming correlates with insulin resistance and PMNL intracellular
calcium ([Ca(2+)]i). Recent studies have attributed additional anti-ischemic and
antioxidative characteristics to the antihypertensive drug, lercanidipine, a
third-generation calcium-channel blocker. The purpose of this study was to
evaluate the possible nontraditional effect of 2 months of lercanidipine
treatment on insulin resistance and on PMNL-related inflammation in EH patients.
METHODS: Non-smoking EH patients with untreated mild-to-moderate high blood
pressure (BP) were included. Low-grade inflammation was reflected by PMNL
apoptosis and by white blood cell (WBC) and PMNL counts. Systemic inflammation
was measured by plasma fibrinogen, C-reactive protein (CRP), and transferrin and
albumin levels. Fasting serum insulin levels served as a marker of insulin
resistance. RESULTS: Two months of lercanidipine treatment showed a significant
decrease in BP, WBC, and PMNL counts, PMNL apoptosis, CRP, and serum insulin
levels, and a significant increase in serum albumin levels. Rates of superoxide
release from PMNLs, WBC and PMNL counts, and insulin levels positively correlated
with mean arterial BP values. CONCLUSION: The use of lercanidipine can be
favorable in EH patients due to its combined anti-PMNL priming and anti
inflammatory effects, in addition to its antihypertensive characteristics.
PMID- 25135159
TI - Transcatheter pulmonary valve replacement.
AB - Transcatheter pulmonary valve replacement (tPVR) has evolved into a viable
alternative to surgical conduit or bioprosthetic valve replacement. This
procedure has paved the way for a more advanced approach to congenital and
structural interventional cardiology. Although many successes have been noted,
there are still a number of challenges with this procedure, including large
delivery systems, the need for a conduit or a bioprosthetic valve as a landing
zone for the valve, optimal timing of the procedure to prevent right ventricular
failure, arrhythmias, and possible death. Research is ongoing to broaden the use
of this technology when treating patients with dilated right ventricular outflow
tracts, and early experience with a self-expanding valve model has been reported.
Affordability is an important factor that must be considered especially in
developing nations. The aim of this review is to emphasize the advancement of
tPVR, the benefits and challenges of valve implantation, the current state, and
the future innovations associated with this approach.
PMID- 25135162
TI - Programmable ionic conductance in a pH-regulated gated nanochannel.
AB - An analytical model for the ionic conductance in a pH-regulated nanochannel gated
by a field effect transistor is derived for the first time. In contrast to the
existing studies, the developed model takes into account the practical effects of
multiple ionic species, surface chemistry reactions, the Stern layer, and
electroosmotic flow. The model is validated by the experimental data of ionic
conductance available in the literature. Results show that the performance of the
field effect control of the ionic conductance in the gated silica nanochannel is
remarkable when the solution pH and salt concentration are low. In addition, the
Stern layer effect on the ionic conductance is significant when the salt
concentration is low.
PMID- 25135160
TI - The Edwards SAPIEN Transcatheter Heart Valve for Calcific Aortic Stenosis: A
Review of the Valve, Procedure, and Current Literature.
AB - The Edwards SAPIENTM transcatheter heart valve (Edwards Lifesciences LLC, Irvine,
CA, USA) is approved by the US Food and drug administration for use in the aortic
position in patients with severe aortic stenosis who are not surgical candidates.
This approval was backed by data from the Placement of AoRTic TraNscathetER Valve
(PARTNER) I clinical trial, which showed the valve to be superior to standard
medical therapy in high-risk nonoperative patients in cohort B of the trial.
Although insertion of the valve is considered to be very safe, stroke, major
vascular complications, and conduction abnormalities are the most frequent
procedural complications. A dedicated team of physicians trained in structural
cardiac interventions, including two interventional cardiologists, an
echocardiographer, and a cardiac surgeon, are involved in every case.
Improvements in valve design and streamlining of the delivery system, as well as
favorable long-term outcomes, will hopefully pave the way for wider patient use
in the future.
PMID- 25135161
TI - Positioning high-dose radiation in multidisciplinary management of unresectable
cholangiocarcinomas: review of current evidence.
AB - Cholangiocarcinoma is a rare malignancy of the bile ducts. The current standard
of care for unresectable nonmetastatic disease is doublet systemic chemotherapy,
which provides a median survival of 11.7 months. Although chemoradiation is a
therapeutic option that provides almost equivalent or superior survival, the lack
of level I evidence presents a major hurdle in routinely recommending it within
multidisciplinary clinics. This mini review presents the current evidence on the
use of chemoradiation for unresectable nonmetastatic cholangiocarcinoma and
rationale for positioning it within multidisciplinary management of unresectable
cholangiocarcinomas.
PMID- 25135164
TI - Epigenetic marks in estrogen receptor alpha CpG island correlate with some
reproductive risk factors in breast cancer.
AB - Reproductive backgrounds, such as age at menarche and menopause, age of first
full-term pregnancy (FFTP), number of full-term deliveries and oral contraceptive
use are main hormone-related risk factors of breast cancer. It seems that the
mentioned factors may affect the risk of breast cancer by enhancing the duration
of exposure to estrogen as a potent carcinogen for breast tissue, but the
molecular mechanism which links each risk factor to breast cancer is unclear.
Estrogen mainly works via its nuclear receptor (ERalpha). As epigenetic
alterations such as CpG methylation are potential links between endogenous or
exogenous exposures and genome, we hypothesized that hormone-related risk factors
may correlate with the epigenetic marks of the ERalpha promoter in breast tumors.
In the present study, the CpG methylation status of the ERalpha gene in 99
samples of breast tumors belonged to women with different reproductive histories
was evaluated. The reproductive history data were collected from patients.
ERalpha CpG methylation was investigated by methylation specific PCR in DNA
samples were obtained from the breast tumors. We could show that some of the
hormone-related risk factors (early FFTP and increased number of pregnancies)
were inversely correlated with epigenetic marks in ERalpha gene in breast tumors.
Other hormone-related risk factors such as age of menarche and menopause and oral
contraceptive use did not show any association with ERalpha methylation. It seems
that pregnancy-related risk factors in comparison with other hormone-related
factors work via different mechanism. As ERalpha methylation is a poor prognosis
marker in breast tumors, its association with some modifiable reproductive risk
factors (FFTP age and numbers of pregnancies) reiterates the importance of
programming reproductive life style not only for prevention of breast cancer but
also in favoring the prognosis of the affected women. The exact molecular
mechanisms of the observed correlation need more investigation in the future.
PMID- 25135165
TI - Major atmospheric emissions from peat fires in Southeast Asia during non-drought
years: evidence from the 2013 Sumatran fires.
AB - Trans-boundary haze events in Southeast Asia are associated with large forest and
peatland fires in Indonesia. These episodes of extreme air pollution usually
occur during drought years induced by climate anomalies from the Pacific (El Nino
Southern Oscillation) and Indian Oceans (Indian Ocean Dipole). However, in June
2013--a non-drought year--Singapore's 24-hr Pollutants Standards Index reached an
all-time record 246 (rated "very unhealthy"). Here, we show using remote sensing,
rainfall records and other data, that the Indonesian fires behind the 2013 haze
followed a two-month dry spell in a wetter-than-average year. These fires were
short-lived (one week) and limited to a localized area in Central Sumatra (1.6%
of Indonesia): burning an estimated 163,336 ha, including 137,044 ha (84%) on
peat. Most burning was confined to deforested lands (82%; 133,216 ha). The
greenhouse gas (GHG) emissions during this brief, localized event were
considerable: 172 +/- 59 Tg CO2-eq (or 31 +/- 12 Tg C), representing 5-10% of
Indonesia's mean annual GHG emissions for 2000-2005. Our observations show that
extreme air pollution episodes in Southeast Asia are no longer restricted to
drought years. We expect major haze events to be increasingly frequent because of
ongoing deforestation of Indonesian peatlands.
PMID- 25135163
TI - Radionuclide imaging of cardiac sympathetic innervation in heart failure:
unlocking untapped potential.
AB - Heart failure (HF) is associated with sympathetic overactivity, which contributes
to disease progression and arrhythmia development. Cardiac sympathetic
innervation imaging can be performed using radiotracers that are taken up in the
presynaptic nerve terminal of sympathetic nerves. The commonly used radiotracers
are (123)I-metaiodobenzylguanidine ((123)I-mIBG) for planar and single-photon
emission computed tomography imaging, and (11)C-hydroxyephedrine for positron
emission tomography imaging. Sympathetic innervation imaging has been used in
assessing prognosis, response to treatment, risk of ventricular arrhythmias and
sudden death and prediction of response to cardiac resynchronization therapy in
patients with HF. Other potential applications of these techniques are in
patients with chemotherapy-induced cardiomyopathy, predicting myocardial recovery
in patients with left ventricular assist devices, and assessing reinnervation
following cardiac transplantation. There is a lack of standardization with
respect to technique of (123)I-mIBG imaging that needs to be overcome for the
imaging modality to gain popularity in clinical practice.
PMID- 25135166
TI - Exosome analysis: a promising biomarker system with special attention to saliva.
AB - Today, exosome-related studies have become a focus in science and technology.
Recently, three scientists won the Nobel Prize for determining the mechanisms of
exosomal transport, making exosomes a promising biomarker system for disease
diagnosis and treatment. This review provides a general introduction of exosomes
and explores the recent progress on the function, application, isolation, and
identification of exosomes as biomarkers in blood and other body fluids,
especially in saliva. Detailed information of exosomal proteins and RNAs is
discussed in the paper because of their ability to determine the function of
exosomes. Due to their noninvasive assessment for quick and convenient diagnosis
of diseases, salivary exosomes may well be promising biomarkers.
PMID- 25135167
TI - A double-pulse approach for electrotransfection.
AB - Gene transfer and expression can be obtained by delivering calibrated electric
pulses on cells in the presence of plasmids coding for the activity of interest.
The electric treatment affects the plasma membrane and induces the formation of a
transient complex between nucleic acids and the plasma membrane. It results in a
delivery of the plasmid in the cytoplasm. Expression is only obtained if the
plasmid is translocated inside the nucleus. This is a key limit in the process.
We previously showed that delivery of a high-field short-duration electric pulse
was inducing a structural alteration of the nuclear envelope. This study
investigates if the double-pulse approach (first pulse to transfer the plasmid to
the cytoplasm, and second pulse to induce the structural alteration of the
envelope) was a way to enhance the protein expression using the green fluorescent
protein as a reporter. We observed that not only the double-pulse approach
induced the transfection of a lower number of cells but moreover, these
transfected cells were less fluorescent than the cells treated only with the
first pulse.
PMID- 25135169
TI - Accelerated biodegradation of selected nematicides in tropical crop soils from
Costa Rica.
AB - Degradation and mineralization behavior of selected nematicides was studied in
soil samples from fields cultivated with banana, potato, and coffee. Degradation
assays in most of the studied soils revealed shorter half-lives for carbofuran
(CBF) and ethoprophos (ETP) in samples with a history of treatment with these
compounds, which may have been caused by enhanced biodegradation. A short half
life value for CBF degradation was also observed in a banana field with no
previous exposure to this pesticide, but with a recent application of the
carbamate insecticide oxamyl, which supports the hypothesis that preexposure to
oxamyl may cause microbial adaptation towards degradation of CBF, an observation
of a phenomenon not yet tested according to the literature reviewed.
Mineralization assays for CBF and terbufos (TBF) revealed that history of
treatment with these nematicides did not cause higher mineralization rates in
preexposed soils when compared to unexposed ones, except in the case of soils
from coffee fields. Mineralization half-lives for soils unexposed to these
pesticides were significantly shorter than most reports in the literature in the
same conditions. Mineralization rates for soils with a previous exposure to these
pesticides were also obtained, adding to the very few reports found. This paper
contributes valuable data to the low number of reports dealing with pesticide
fate in soils from tropical origin.
PMID- 25135168
TI - Toxicity and oxidative stress induced by used and unused motor oil on freshwater
microalga, Pseudokirchneriella subcapitata.
AB - Although used motor oil from automobiles is one of the major pollutants through
storm water in urban environments leading to contamination of water bodies, very
little information is available on its toxicity towards growth of microalgae.
Also, to our knowledge, there are no data on the used motor oil-induced oxidative
stress in microalgae. We therefore investigated the toxicity of used and fresh
motor oil on growth and antioxidant enzymes of a microalga, Pseudokirchneriella
subcapitata. In general, used oil was more toxic to the alga than fresh oil. Used
oil at 0.20 % inhibited algal growth, measured in terms of chlorophyll a, by 44 %
while fresh oil was nontoxic up to 2.8 %. Water-accommodated fraction (WAF) of
the used oil at >50 % concentration exhibited significant toxicity while WAF from
fresh oil was nontoxic even up to 100 %. Used oil and its WAF, even at lower
concentrations, increased the levels of antioxidant enzymes indicating algal
response to the toxicity stress. When the alga was exposed to WAF from fresh
motor oil, no alterations in the antioxidant enzyme levels were evident. The
present investigation suggests that contamination of aquatic systems with used
oil could potentially affect the ecosystem health via disruption of primary
producers that are located at the base of the food chain.
PMID- 25135170
TI - Effects on inorganic nitrogen compounds release of contaminated sediment
treatment with in situ calcium nitrate injection.
AB - Notable releases of nitrate, nitrite, and ammonia are often observed in
contaminated sediment treatment works implementing in situ calcium nitrate
injection. In order to provide extended information for making best decision of
employing this in situ sediment remediation technology, in this study the
releases of nitrate, nitrite, and ammonia from the sediment after the calcium
nitrate addition operation was investigated in column setups designed to simulate
the scenarios of a stagnant water (e.g., a pound or small lake) and a tidal
influenced water (e.g., a river mouth), respectively. Comparison with published
aquatic toxicity data or authorized criteria was conducted to assess if there is
any toxic effect that might be induced. Along with the vigorous N2 emission due
to the denitrification reactions which occurred in the treated sediment, external
loaded nitrate, intermediately produced nitrite, and indigenous ammonia in the
sediment showed being mobilized and released out. Their promoted release and fast
buildup in the overlying water to an excessive level probably cause toxic effects
to sensitive freshwater living species. Among them, the potential ecological risk
induced by the promoted sediment ammonia release is the greatest, and cautions
shall be raised for applying the calcium nitrate injection in ammonia-rich
sediments. The caused impacts shall be less violent in a tidal-influenced water
body, and comparatively, the continuous and fast accumulation of the released
inorganic nitrogen compounds in a stagnant water body might impose severer
influences to the ecosystem until being further transferred to less harmful
forms.
PMID- 25135171
TI - Transformation of anthracene on various cation-modified clay minerals.
AB - In this study, anthracene was employed as a probe to explore the potential
catalytic effect of clay minerals in soil environment. Clay minerals saturated
with various exchangeable cations were tested. The rate of anthracene
transformation follows the order: Fe-smectite >> Cu-smectite > Al-smectite ~ Ca
smectite ~ Mg-smectite ~ Na-smectite. This suggests that transition-metal ions
such as Fe(III) play an important role in anthracene transformation. Among
Fe(III)-saturated clays, Fe(III)-smectite exhibits the highest catalytic activity
followed by Fe(III)-illite, Fe(III)-pyrophyllite, and Fe(III)-kaolinite, which is
in agreement with the interlayer Fe(III) content. Moreover, effects by two common
environmental factors, pH and relative humidity (RH), were evaluated. With an
increase in pH or RH, the rate of anthracene transformation decreases rapidly at
first and then is leveled off. GC-MS analysis identifies that the final product
of anthracene transformation is 9,10-anthraquinone, a more bioavailable molecule
compared to anthracene. The transformation process mainly involves cation-pi
bonding, electron transfer leading to cation radical, and further oxidation by
chemisorbed O2. The present work provides valuable insights into the abiotic
transformation and the fate of PAHs in the soil environment and the development
of contaminated land remediation technologies.
PMID- 25135172
TI - Mesh repair versus non-mesh repair for strangulated inguinal hernia: systematic
review with meta-analysis.
AB - BACKGROUND: The optimal technique to cure strangulated inguinal hernia remains
controversial. The use of mesh in cases of strangulated hernia is still debated
due to the potential risk of infection. OBJECTIVE: This systematic review aimed
to determine whether or not the mesh repair technique is associated with a higher
risk of surgical site infection than non-mesh techniques for strangulated
inguinal hernias in adults. METHODS: An electronic search of the relevant
literature was performed on 15 December 2012 using the following databases:
MEDLINE, the Cochrane Library, Scopus, Embase, and the Web of Science. Articles
reporting a comparison between the mesh repair technique and a non-mesh technique
to treat strangulated inguinal hernias in adults, and published in the English or
French language in a peer-reviewed journal, were considered for analysis. The
quality of randomized controlled trials (RCTs) was assessed using the Jadad
scoring system. To assess the quality of non-randomized trials, we used the
Methodological Index for Non-Randomized Studies (MINORS). RESULTS: A total of 232
papers was found in the initial search; nine were included in the meta-analysis.
The wound infection rate in the mesh repair technique group was lower than in the
control group, with a trend towards significance (odds ratio [OR] 0.46, 95 %
confidence interval [CI] 0.20-1.07; p = 0.07). The hernia recurrence rate was
lower in the mesh repair group (OR 0.2, 95 % CI 0.05-0.78; p = 0.02). CONCLUSION:
The mesh repair technique is a good option for the treatment of strangulated
inguinal hernias in adults, giving an acceptable wound infection rate and fewer
recurrences than non-mesh repair. Our study does not allow us to recommend the
use of mesh in cases of bowel resection. We emphasize that, except the two RCTs,
the results are predicated on patient selection bias by careful surgeons. Further
RCTs are required to obtain more powerful evidence-based data.
PMID- 25135173
TI - Evaluation of QOL after proximal gastrectomy using a newly developed assessment
scale (PGSAS-45).
AB - BACKGROUND: Proximal gastrectomy with esophagogastrostomy (PGEG) has been widely
applied as a comparatively simple method. In this study, we used a questionnaire
survey to evaluate the influence of various surgical factors on post-operative
quality of life (QOL) after PGEG. METHODS: In this post-gastrectomy syndrome
assessment study, we analyzed QOL in 2,368 cases. Among these, 193 had undergone
proximal gastrectomy and 115 had undergone PGEG. The Post-Gastrectomy Syndrome
Assessment Scale (PGSAS)-45 is a questionnaire consisting of 45 items, including
the SF-8, the Gastrointestinal Symptom Rating Scale (GSRS), and other symptom
items seemed to be specific to post-gastrectomy. The 23 symptom items were
composed of seven symptom subscales (SS), including esophageal reflux, abdominal
pain, and meal-related distress. These seven SS, total symptom score, ingested
amount of food per meal, necessity for additional meals, quality of ingestion SS,
ability to work, dissatisfaction with symptoms, dissatisfaction with the meal,
dissatisfaction with working, dissatisfaction with daily life SS and change in
body weight were evaluated as main outcome measures. In PGEG cases, we evaluated
the influence on QOL of various surgical factors, such as procedures to prevent
gastroesophageal regurgitation and size of the remnant stomach. RESULTS: The
scores for esophageal reflux and dissatisfaction with the meal were higher in
patients who had not undergone an anti-reflux procedure. In most cases, the
preserved remnant stomach was more than two-thirds the size of the pre-operative
stomach. When comparing patients with a remnant stomach two-thirds the pre
operative size and those with more than three-quarters, the diarrhea SS and
necessity for additional meals scores were lower in the group with more than
three-quarters. The indigestion, constipation, and abdominal pain subscales, and
the total symptom score, were higher in patients who had not undergone pyloric
bougie than in those who had. CONCLUSION: These results indicated that QOL was
better in patients with a large remnant stomach. Procedures to prevent
gastroesophageal reflux, and the use of pyloric bougie as a complementary
drainage procedure, were considered effective ways to reduce the deterioration of
QOL.
PMID- 25135174
TI - What is the better choice for T1b gallbladder cancer: simple versus extended
cholecystectomy.
AB - BACKGROUND: There is debate over whether T1b gallbladder cancer (GBC) should be
treated by simple cholecystectomy (SC) or by extended cholecystectomy (EC). The
aim of this study is to compare and analyze the results of these two procedures.
PATIENTS AND METHODS: The archived medical records of 805 patients with GBC who
had undergone surgical resection in Asan Medical Center, or were referred from
other hospitals after undergoing surgery, between 1997 and 2010 were
retrospectively reviewed. Of these, 85 patients were diagnosed with pathologic
stage T1b (muscular layer) GBC. By using propensity scoring, the EC group and the
SC group were matched in the proportion of 1:2; so, 54 patients were enrolled in
this study. RESULTS: Among the 54 pathologic stage T1b cancer patients, SC was
performed in 36 (66.7 %) and EC in 18 (33.4 %). The mean operation time and
hospital stay after surgery of the SC group was significantly shorter than in the
EC group (83.2 vs. 356.4 min, 7.8 vs. 15.2 days; both p = 0.000). Disease
recurrence was noted in four cases (11.1 %), all in the SC group; 50 % of
recurred patients experienced recurrence at the lymph node. There was no
significant intergroup difference in the 5-year survival rate (5-YSR) (88.8 % for
SC vs. 93.3 % for EC, p = 0.521). CONCLUSIONS: In this study, for stage T1b GBC,
both EC and SC offered similar cure rates. However, recurrence is associated with
SC and inadequate lymph node dissection (LND). Therefore, EC including regional
LND may be justified and preferred because of the possibility of lymph node
metastasis and the accurate assessment of stage (LN status), except that the
patients have a high risk of operation.
PMID- 25135175
TI - Congenital anomalies in low- and middle-income countries: the unborn child of
global surgery.
AB - Surgically correctable congenital anomalies cause a substantial burden of global
morbidity and mortality. These anomalies disproportionately affect children in
low- and middle-income countries (LMICs) due to sociocultural, economic, and
structural factors that limit the accessibility and quality of pediatric surgery.
While data from LMICs are sparse, available evidence suggests that the true human
and financial cost of congenital anomalies is grossly underestimated and that
pediatric surgery is a cost-effective intervention with the potential to avert
significant premature mortality and lifelong disability.
PMID- 25135176
TI - Liver-to-spleen ratio as an index of chronic liver diseases and safety of
hepatectomy: a pilot study.
AB - BACKGROUND: Hepatic failure is a main cause of death after hepatectomy. Accurate
preoperative evaluation of functional liver reserve is the key to ensure safe
resection. Studies have found that the spleen would gradually enlarge as chronic
liver disease worsened. This study was designed to determine whether preoperative
liver-to-spleen ratio (LSR) would be an indicator to evaluate severity of liver
disease and predict safety of hepatectomy. METHODS: The volumes of liver and
spleen were evaluated on computed tomography scan in 67 patients who received
partial hepatectomy. Preoperative LSR was calculated. Statistical analysis was
conducted to examine the relationship between LSR and the degree of chronic liver
disease. Ability of LSR to predict the safety of hepatectomy also was evaluated.
RESULTS: LSR had a negative correlation with the degree of chronic liver diseases
(r = -0.606, P < 0.0001). LSR = 3.22 was the cutoff point for predicting
posthepatectomy complications and inadequacy. AUC, sensitivity, and specificity
for predicting posthepatectomy complications and inadequacy respectively were
0.830 (95 % confidence interval [CI] 0.715-0.950, P < 0.0001), 69.6, 93.2 %, and
0.863 (95 % CI 0.777-0.949, P < 0.0001), 68.8, 84.3 %. Multivariate analysis
showed that LSR = 3.22 was the factor that affected both posthepatectomy
complications and liver inadequacy. CONCLUSIONS: Preoperative LSR score
correlated well with the degree of chronic liver diseases, and it probably help
us to improve the safety of hepatectomy.
PMID- 25135177
TI - The extent of hepatectomy does not affect physical QOL in patients with HCC:
reply.
PMID- 25135178
TI - Cardiovascular and cancer events in hyper-high-density lipoprotein
cholesterolemic patients: a post hoc analysis of the MEGA study.
AB - BACKGROUND: The prognosis for hyper-high-density lipoprotein (HDL)
cholesterolemic patients has not been fully elucidated. We conducted a post hoc
analysis of MEGA study data to investigate prospectively the incidence of
cardiovascular events and cancer in hyper-HDL cholesterolemic patients. METHODS:
A total of 7832 patients with mild hypercholesterolemia were randomly allocated
to either the National Cholesterol Education Program step 1 diet alone (n = 3966)
or the diet plus pravastatin (n = 3866) and followed for 5 years. The incidences
of coronary heart disease (CHD), CHD plus cerebral infarction (CI),
cardiovascular disease (CVD), and cancer were calculated using the Cox
proportional hazards model according to the level of HDL cholesterol (HDL-C).
RESULTS: CHD incidence was lower in patients with HDL-C >60-90 mg/dL (-52%, p =
0.0018) and HDL-C > 90 mg/dL (-46%, p = 0.4007) than in patients with HDL-C <= 60
mg/dL. The incidences of CHD, CHD plus CI, and CVD were significantly lower in
patients with HDL-C >60-90 mg/dL than in those with HDL-C <= 60 mg/dL in both
diet-alone and diet-plus-pravastatin groups. Cancer incidence was not increased
in patients with HDL-C >60-90 mg/dL. CONCLUSION: Patients not receiving statin
therapy should aim for a target HDL-C of between 60 and 90 mg/dL to achieve a
significant reduction in CHD without the occurrence of adverse events. TRIAL
REGISTRATION: Clinical trials.gov NCT00211705.
PMID- 25135180
TI - Phenytoin-induced methaemoglobinaemia in a patient with glioblastoma multiforme.
PMID- 25135179
TI - Convergence of a specialized root trait in plants from nutrient-impoverished
soils: phosphorus-acquisition strategy in a nonmycorrhizal cactus.
AB - In old, phosphorus (P)-impoverished habitats, root specializations such as
cluster roots efficiently mobilize and acquire P by releasing large amounts of
carboxylates in the rhizosphere. These specialized roots are rarely mycorrhizal.
We investigated whether Discocactus placentiformis (Cactaceae), a common species
in nutrient-poor campos rupestres over white sands, operates in the same way as
other root specializations. Discocactus placentiformis showed no mycorrhizal
colonization, but exhibited a sand-binding root specialization with rhizosheath
formation. We first provide circumstantial evidence for carboxylate exudation in
field material, based on its very high shoot manganese (Mn) concentrations, and
then firm evidence, based on exudate analysis. We identified predominantly oxalic
acid, but also malic, citric, lactic, succinic, fumaric, and malonic acids. When
grown in nutrient solution with P concentrations ranging from 0 to 100 MUM, we
observed an increase in total carboxylate exudation with decreasing P supply,
showing that P deficiency stimulated carboxylate release. Additionally, we tested
P solubilization by citric, malic and oxalic acids, and found that they
solubilized P from the strongly P-sorbing soil in its native habitat, when the
acids were added in combination and in relatively low concentrations. We conclude
that the sand-binding root specialization in this nonmycorrhizal cactus functions
similar to that of cluster roots, which efficiently enhance P acquisition in
other habitats with very low P availability.
PMID- 25135181
TI - Protoplast fusion enhances lignocellulolytic enzyme activities in Trichoderma
reesei.
AB - Protoplast fusion was used to obtain a higher production of lignocellulolytic
enzymes with protoplast fusion in Trichoderma reesei. The fusant strain T. reesei
JL6 was obtained from protoplast fusion from T. reesei strains QM9414, MCG77, and
Rut C-30. Filter paper activity of T. reesei JL6 increased by 18% compared with
that of Rut C-30. beta-Glucosidase, hemicellulase and pectinase activities of T.
reesei JL6 were also higher. The former activity was 0.39 Uml(-1), while those of
QM9414, MCG77, and Rut C-30 were 0.13, 0.11, and 0.16 Uml(-1), respectively.
Pectinase and hemicellulase activities of JL6 were 5.4 and 15.6 Uml(-1),
respectively, which were slightly higher than those of the parents. The effects
of corn stover and wheat bran carbon sources on the cellulase production and
growth curve of T. reesei JL6 were also investigated.
PMID- 25135182
TI - Adult-onset vanishing white matter disease as differential diagnosis of primary
progressive multiple sclerosis: a case report.
AB - We report the case of a 42-year-old woman with a slowly progressive cerebellar
syndrome. In contrast to a relatively mild clinical presentation, the magnetic
resonance imaging (MRI) showed extensive leukencephalopathy with cystic
degeneration. Initially primary progressive multiple sclerosis (PPMS) was
suspected. Additional diffusion-weighted imaging revealed restricted diffusion in
the white matter lesions with a reduced apparent diffusion coefficient. Genetic
testing showed vanishing white matter disease (VWM) with c.260C>T EIF2B3
mutation. In conclusion, in cases with relatively mild symptoms and extensive
white matter lesions, adult-onset VWM should be considered as differential
diagnosis of PPMS and diffusion-weighted imaging may be helpful to identify
suspected cases.
PMID- 25135183
TI - Allopurinol initiation and change in blood pressure in older adults with
hypertension.
AB - Hypertension is a key risk factor for cardiovascular disease, and new treatments
are needed. Uric acid reduction lowers blood pressure (BP) in adolescents,
suggesting a direct pathophysiological role in the development of hypertension.
Whether the same relationship is present in older adults is unknown. We explored
change in BP after allopurinol initiation using data from the UK Clinical
Practice Research Datalink. Data were extracted for patients with hypertension
aged >65 years who were prescribed allopurinol with pretreatment and during
treatment BP readings. Data from comparable controls were extracted. The change
in BP in patients with stable BP medication was the primary outcome and was
compared between groups. Regression analysis was used to adjust for potential
confounding factors, and a propensity-matched sample was generated. Three hundred
sixty-five patients who received allopurinol and 6678 controls were included. BP
fell in the allopurinol group compared with controls (between-group difference in
systolic and diastolic BP: 2.1 mm Hg; 95% confidence interval, -0.6 to 4.8; and
1.7 mm Hg; 95% confidence interval, 0.4-3.1, respectively). Allopurinol use was
independently associated with a fall in both systolic and diastolic BP on
regression analysis (P<0.001). Results were consistent in the propensity-matched
sample. There was a trend toward greater fall in BP in the high-dose allopurinol
group, but change in BP was not related to baseline uric acid level. Allopurinol
use is associated with a small fall in BP in adults. Further studies of the
effect of high-dose allopurinol in adults with hypertension are needed.
PMID- 25135184
TI - Nitric oxide inhibition of endothelin-1 release in the vasculature: in vivo
relevance of in vitro findings.
PMID- 25135186
TI - Amplified fluorescence quenching of lucigenin self-assembled inside
silica/chitosan nanoparticles by Cl-.
AB - Fluorescence sensing of an analyte based on the fluorophore collective effect is
a reliable, sensitive sensing approach. Many ultralow targets can be detected on
the basis of the high sensitivity and signal amplification of the fluorescence
sensing system. However, the complicated synthesis procedures, harsh conditions
required to design and control the fluorescence molecular probes and conjugated
chain length, and the higher cost of synthesis are still challenges. To address
these issues, we developed a simple, rapid, and sensitive collective effect based
fluorescence sensing platform. In this sensing platform, the fluorophore unit was
self-assembled on the wall of the nanopores of the porous structural
silica/chitosan nanoparticles (SCNPs) on the basis of the electrostatic
interaction and supermolecular interaction between the fluorophores and SiO(-)
groups and chitosan. Since these self-assembled fluorophores are close enough to
communicate with each other on the basis of the space confinement effect of the
pore size, many fluorophore units could interact with a single analyte and
produce an amplified fluorescence sensing ability. Chloride ion, an important
anion in biological fluids, and lucigenin, a typical fluorescent dye, were used
as a model to confirm the proof-of-concept strategy. Our results showed that,
compared to free-state lucigenin in solution, the assembled-state lucigenin in
SCNPs presented an about 10-fold increase in its Stern-Volmer constant when the
concentration of Cl(-) was lower than 10 mM, and this fluorescence nanosensor was
also successfully used to sense the chloride ion in living cells.
PMID- 25135185
TI - Setting thresholds to varying blood pressure monitoring intervals differentially
affects risk estimates associated with white-coat and masked hypertension in the
population.
AB - Outcome-driven recommendations about time intervals during which ambulatory blood
pressure should be measured to diagnose white-coat or masked hypertension are
lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years;
48.4% women) enrolled in 12 population studies, using >=140/>=90, >=130/>=80,
>=135/>=85, and >=120/>=70 mm Hg as hypertension thresholds for conventional, 24
hour, daytime, and nighttime blood pressure. White-coat hypertension was
hypertension on conventional measurement with ambulatory normotension, the
opposite condition being masked hypertension. Intervals used for classification
of participants were daytime, nighttime, and 24 hours, first considered
separately, and next combined as 24 hours plus daytime or plus nighttime, or plus
both. Depending on time intervals chosen, white-coat and masked hypertension
frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively.
During 91 046 person-years, 729 participants experienced a cardiovascular event.
In multivariable analyses with normotension during all intervals of the day as
reference, hazard ratios associated with white-coat hypertension progressively
weakened considering daytime only (1.38; P=0.033), nighttime only (1.43;
P=0.0074), 24 hours only (1.21; P=0.20), 24 hours plus daytime (1.24; P=0.18), 24
hours plus nighttime (1.15; P=0.39), and 24 hours plus daytime and nighttime
(1.16; P=0.41). The hazard ratios comparing masked hypertension with normotension
were all significant (P<0.0001), ranging from 1.76 to 2.03. In conclusion,
identification of truly low-risk white-coat hypertension requires setting
thresholds simultaneously to 24 hours, daytime, and nighttime blood pressure.
Although any time interval suffices to diagnose masked hypertension, as proposed
in current guidelines, full 24-hour recordings remain standard in clinical
practice.
PMID- 25135189
TI - TRPV-ing up pain for a long life.
PMID- 25135190
TI - New therapeutic options for anxiety and mood disorders.
PMID- 25135188
TI - Mapping of the chromosomal amplification 1p21-22 in bladder cancer.
AB - BACKGROUND: The aim of the study was to characterize a recurrent amplification at
chromosomal region 1p21-22 in bladder cancer. METHODS: ArrayCGH (aCGH) was
performed to identify DNA copy number variations in 7 clinical samples and 6
bladder cancer cell lines. FISH was used to map the amplicon at 1p21-22 in the
cell lines. Gene expression microarrays and qRT-PCR were used to study the
expression of putative target genes in the region. RESULTS: aCGH identified an
amplification at 1p21-22 in 10/13 (77%) samples. The minimal region of the
amplification was mapped to a region of about 1 Mb in size, containing a total of
11 known genes. The highest amplification was found in SCaBER squamous cell
carcinoma cell line. Four genes, TMED5, DR1, RPL5 and EVI5, showed significant
overexpression in the SCaBER cell line compared to all the other samples tested.
Oncomine database analysis revealed upregulation of DR1 in superficial and
infiltrating bladder cancer samples, compared to normal bladder. CONCLUSIONS: In
conclusions, we have identified and mapped chromosomal amplification at 1p21-22
in bladder cancer as well as studied the expression of the genes in the region.
DR1 was found to be significantly overexpressed in the SCaBER, which is a model
of squamous cell carcinoma. However, the overexpression was found also in a
published clinical sample cohort of superficial and infiltrating bladder cancers.
Further studies with more clinical material are needed to investigate the role of
the amplification at 1p21-22.
PMID- 25135192
TI - Test-retest reliability of second lactate turnpoint using two different criteria
in competitive cyclists.
AB - The aim of this study was to determine the relative and absolute reliability of
second lactate turnpoint using fixed and individual blood lactate method in
competitive cyclists. Twenty-eight male, well-trained cyclists (30.2 +/- 10.1
years, 72.0 +/- 7.4 kg, 177.3 +/- 4.7 cm) were recruited to participate in this
study. Cyclists completed two incremental cycling tests to exhaustion over a
period of 7 days to determine their peak power output, maximal oxygen uptake,
maximal heart rate, maximal blood lactate concentration and two lactate turnpoint
criteria. The fixed blood concentration criterion (3.5 mM) and an individual
criterion were assessed by a lactate-power curve, considering power output, heart
rate and oxygen uptake. The main finding of this study was that both lactate
turnpoint criteria showed identical low within-subject variation for power output
(2.8% coefficient of variation). High values for test-retest correlations ranging
from r = 0.70 to r = 0.94 were found for all variables in both threshold
criteria. In conclusion, the individual and fixed method to determine the second
lactate turnpoint showed similar high absolute and relative reliability in
competitive cyclists.
PMID- 25135191
TI - Long-term effects of a collaborative care intervention on process of care in
family practices in Germany: a 24-month follow-up study of a cluster randomized
controlled trial.
AB - OBJECTIVE: The aims of this study were (1) to assess the long-term effects of a
collaborative care intervention for patients with depression on process of care
outcomes, and (2) to describe whether case management was continued after the end
of the original one-year intervention. METHODS: This 24-month follow-up of a
randomized controlled trial took place 12 months after the end of the 1-year
intervention. Data collection occurred by means of self-rating questionnaires and
from medical records. We calculated linear mixed and logistic generalized
estimating equation models. RESULTS: Of the 626 patients included at baseline,
439 (70.1%) participated in this follow-up. Intervention recipients gave higher
ratings than control recipients in terms of mean overall Patient Assessment of
Chronic Illness Care (PACIC) scores (3.12 vs. 2.86; P = .019), but no difference
was found in medication adherence (mean Morisky score 2.59 vs. 2.65, P = .56),
prescribed antidepressant medications (60.2% vs. 55.1%; P = .25), visits to the
family physician (15.96 vs. 14.46, P = .58) or mental health specialist (3.01 vs.
2.94, P = .94) over the 12 month follow-up period. Case management was continued
for 47 (22.5%) selected intervention patients after the original intervention had
ended. CONCLUSION: At 24 months, intervention and control recipients had
different PACIC ratings, but other process of care outcomes did not differ.
PRACTICE IMPLICATIONS: The main effects of the intervention are apparent at 12
months.
PMID- 25135193
TI - Mitochondrial dysfunction mediated by cytoplasmic acidification results in pollen
tube growth cessation in Pyrus pyrifolia.
AB - The length of pollen tubes grown in synthetic media is normally shorter than
those grown in vivo. However, the mechanism(s) underlying the cessation of pollen
tube growth under culture conditions remain(s) largely unknown. Here, we report a
previously unknown correlation between vacuolar function and the cell's ability
to sustain mitochondrial functions in pear pollen tubes. The pear pollen tubes in
vitro grew slowly after 15 hours post-cultured (HPC) and nearly ceased growth at
18 HPC. There was increased malondialdehyde content and membrane ion leakage at
15 HPC compared with 12 HPC. Furthermore, cytoplasmic acidification mainly
mediated by decreased vacuolar H(+)-ATPase [V-ATPase, Enzyme Commission (EC)
3.6.1.3] activity was observed in pollen tubes after 15 HPC, and this further
resulted in mitochondrial dysfunction, including mitochondrial structure
disruption, mitochondrial membrane potential collapse and decreases in both
oxygen consumption and ATP production. Our findings suggest that vacuoles and
mitochondria intimately linked in regulating pollen tube elongation.
PMID- 25135194
TI - The use of research evidence on patient preferences in health care decision
making: issues, controversies and moving forward.
AB - Patient preferences are increasingly considered important in health care decision
making. The consideration of patient preferences is mostly put into practice by
giving patients a seat at the decision-making table, instead of using research
evidence on patient preferences. The consideration of research evidence on
patient preferences is justified and relevant for several reasons. The current
limited use of this type of evidence suggests, however, that barriers for its use
exist. This paper provides an overview of the issues and controversies related to
the use of research evidence on patient preferences. Furthermore, an agenda for
research and practice is proposed. The paper focuses on two decision contexts,
clinical practice guideline development and reimbursement decision-making.
PMID- 25135187
TI - The bacterial translation stress response.
AB - Throughout their life, bacteria need to sense and respond to environmental
stress. Thus, such stress responses can require dramatic cellular reprogramming,
both at the transcriptional as well as the translational level. This review
focuses on the protein factors that interact with the bacterial translational
apparatus to respond to and cope with different types of environmental stress.
For example, the stringent factor RelA interacts with the ribosome to generate
ppGpp under nutrient deprivation, whereas a variety of factors have been
identified that bind to the ribosome under unfavorable growth conditions to shut
down (RelE, pY, RMF, HPF and EttA) or re-program (MazF, EF4 and BipA)
translation. Additional factors have been identified that rescue ribosomes
stalled due to stress-induced mRNA truncation (tmRNA, ArfA, ArfB), translation of
unfavorable protein sequences (EF-P), heat shock-induced subunit dissociation
(Hsp15), or antibiotic inhibition (TetM, FusB). Understanding the mechanism of
how the bacterial cell responds to stress will not only provide fundamental
insight into translation regulation, but will also be an important step to
identifying new targets for the development of novel antimicrobial agents.
PMID- 25135195
TI - Reconsolidation of a well-learned instrumental memory.
AB - Once consolidated, memories are dynamic entities that go through phases of
instability in order to be updated with new information, via a process of
reconsolidation. The phenomenon of reconsolidation has been demonstrated in a
wide variety of experimental paradigms. However, the memories underpinning
instrumental behaviors are currently not believed to reconsolidate. We show that
well-learned lever pressing in rats does undergo reconsolidation, which can be
disrupted by systemic administration of the noncompetitive N-methyl-D-aspartate
receptor (NMDAR) antagonist (+)-5-methyl-10,11-dihydro-SH-dibenzo[a,d]cyclohepten
5,10-imine maleate (MK-801) when administered prior to a switch to a variable,
but not fixed, ratio schedule. Disruption of reconsolidation resulted in a
reduction in long-term lever pressing performance and diminished the sensitivity
of behavior to contingency change. Further investigation demonstrated that
expression of the reconsolidation impairment was not affected by outcome value,
implying a deficit in a stimulus-response (S-R) process. The ability to disrupt
the performance of well-learned instrumental behaviors is potentially of great
importance in the development of reconsolidation-based clinical treatments for
conditions that involve compulsive seeking behaviors.
PMID- 25135196
TI - Protein degradation by ubiquitin-proteasome system in formation and labilization
of contextual conditioning memory.
AB - The ubiquitin-proteasome system (UPS) of protein degradation has been evaluated
in different forms of neural plasticity and memory. The role of UPS in such
processes is controversial. Several results support the idea that the activation
of this system in memory consolidation is necessary to overcome negative
constrains for plasticity. In this case, the inhibition of the UPS during
consolidation impairs memory. Similar results were reported for memory
reconsolidation. However, in other cases, the inhibition of UPS had no effect on
memory consolidation and reconsolidation but impedes the amnesic action of
protein synthesis inhibition after retrieval. The last finding suggests a
specific action of the UPS inhibitor on memory labilization. However, another
interpretation is possible in terms of the synthesis/degradation balance of
positive and negative elements in neural plasticity, as was found in the case of
long-term potentiation. To evaluate these alternative interpretations, other
reconsolidation-interfering drugs than translation inhibitors should be tested.
Here we analyzed initially the UPS inhibitor effect in contextual conditioning in
crabs. We found that UPS inhibition during consolidation impaired long-term
memory. In contrast, UPS inhibition did not affect memory reconsolidation after
contextual retrieval but, in fact, impeded memory labilization, blocking the
action of drugs that does not affect directly the protein synthesis. To extend
these finding to vertebrates, we performed similar experiments in contextual fear
memory in mice. We found that the UPS inhibitor in hippocampus affected memory
consolidation and blocked memory labilization after retrieval. These findings
exclude alternative interpretations to the requirement of UPS in memory
labilization and give evidence of this mechanism in both vertebrates and
invertebrates.
PMID- 25135199
TI - Racial disparity in metastatic renal cell cancer: the pharmaco-anthropology of
sunitinib.
PMID- 25135200
TI - Serious hepatic complications of selective internal radiation therapy with
yttrium-90 microsphere radioembolization for unresectable liver tumors.
AB - AIM: Selective internal radiation therapy with yttrium-90 microsphere
radioembolization has been used to treat unresectable liver tumors and its acute
toxicity has been well described. Subacute and long-term hepatic complications
related to radioembolization however may be underreported in the literature. This
retrospective study describes the incidence and sequelae of serious hepatic
complications in patients who underwent radioembolization for unresectable liver
tumors. METHODS: A retrospective review of clinical notes of patients who
received radioembolization for unresectable liver tumors from 2001 to 2011 at two
Australian institutions was performed to identify those who developed clinically
significant hepatic complications. Relevant clinical data were obtained and
analyzed to determine their incidence and sequelae. RESULTS: A total of 205
patients were identified, of whom 10 (4.9%) developed serious hepatic
complications with 7 (3.4%) attributable to radioembolization-induced liver
disease. None had preexisting underlying liver disease or progressive hepatic
metastases at the time of developing hepatic complication. The median time to the
onset of hepatic complications was 3.5 months (range 1-67 months); six patients
had a complete resolution eventually, including one patient who subsequently
underwent hepatic metastasectomy safely. Three patients died as a result of
fulminant hepatic failure. CONCLUSION: Selective internal radiation therapy with
radioembolization was associated with serious hepatic complications with an
incidence of 4.9% and a mortality rate of 1.5% in 205 patients from two
Australian institutions. The risk of serious hepatic toxicity therefore needs to
be discussed when counseling patients regarding this potential treatment option.
PMID- 25135197
TI - Safety signals as instrumental reinforcers during free-operant avoidance.
AB - Safety signals provide "relief" through predicting the absence of an aversive
event. At issue is whether these signals also act as instrumental reinforcers.
Four experiments were conducted using a free-operant lever-press avoidance
paradigm in which each press avoided shock and was followed by the presentation
of a 5-sec auditory safety signal. When given a choice between two levers in
Experiment 1, both avoiding shock, rats preferentially responded on the lever
that produced the safety signal as feedback, even when footshock was omitted.
Following avoidance training with a single lever in Experiment 2, removal of the
signal led to a decrease in avoidance responses and an increase in responses
during the safety period normally denoted by the signal. These behavioral changes
demonstrate the dual conditioned reinforcing and fear inhibiting properties of
the safety signal. The associative processes that support the reinforcing
properties of a safety signal were tested using a novel revaluation procedure.
Prior experience of systemic morphine during safety signal presentations resulted
in an increased rate of avoidance responses to produce the safety signal during a
drug-free extinction test, a finding not seen with d-amphetamine in Experiment 3.
Morphine revaluation of the safety signal was repeated in Experiment 4 followed
by a drug-free extinction test in which responses did not produce the signal for
the first 10 min of the session. Instrumental avoidance in the absence of the
signal was shown to be insensitive to prior signal revaluation, suggesting that
the signal reinforces free-operant avoidance behavior through a habit-like
mechanism.
PMID- 25135198
TI - Understanding functional miRNA-target interactions in vivo by site-specific
genome engineering.
AB - MicroRNA (miRNA) target recognition is largely dictated by short 'seed'
sequences, and single miRNAs therefore have the potential to regulate a large
number of genes. Understanding the contribution of specific miRNA-target
interactions to the regulation of biological processes in vivo remains
challenging. Here we use transcription activator-like effector nuclease (TALEN)
and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9
technologies to interrogate the functional relevance of predicted miRNA response
elements (MREs) to post-transcriptional silencing in zebrafish and Drosophila. We
also demonstrate an effective strategy that uses CRISPR-mediated homology
directed repair with short oligonucleotide donors for the assessment of MRE
activity in human cells. These methods facilitate analysis of the direct
phenotypic consequences resulting from blocking specific miRNA-MRE interactions
at any point during development.
PMID- 25135201
TI - Epidermal growth factor receptor-tyrosine kinase inhibitors in advanced squamous
cell carcinoma of the lung: a meta-analysis.
AB - AIM: Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor
receptor (EGFR) are well established in treating metastatic pulmonary
adenocarcinoma, especially patients with activating EGFR mutations. EGFR
mutations are rare in pulmonary squamous cell carcinomas (SCCs). There are
conflicting data supporting the efficacy of EGFR-TKIs in advanced lung SCC. We
analyzed the impact of EGFR-TKIs on progression-free survival (PFS) and overall
survival (OS) in unselected patients with lung SCC. METHODS: We searched for
randomized controlled trials (RCTs) comparing EGFR-TKIs alone with placebo in
patients with metastatic non-small cell lung cancer. RCTs in all settings (front
line/maintenance/subsequent) were included. The primary outcome was OS in the SCC
population. We used published hazard ratios (HRs), and when unavailable,
unpublished data were sought. Pooled estimates of treatment effect on OS and PFS
were calculated using the fixed-effects inverse variance weighted method.
RESULTS: Eight eligible RCTs were included: 2 first-line, 6 second-line or
beyond, evaluating 1781 patients. Data were available for OS in four studies
(second-line; N=1420) and for PFS in four studies (3 second-line, 1 first-line;
N=788). EGFR-TKIs significantly prolonged OS with a HR of 0.88 (95% confidence
interval [CI] 0.78-1.00, P=0.04), and significantly prolonged PFS with a HR of
0.77 (95% CI 0.65-0.92, P=0.004). CONCLUSION: EGFR mutations are rare in lung
SCC. However, EGFR-TKIs have a modest therapeutic effect compared to placebo in
unselected patients with advanced pulmonary SCC, and can be considered in these
patients. EGFR-mutation-independent mechanisms may explain efficacy of EGFR
inhibitors in this setting.
PMID- 25135204
TI - Knockdown of alphaIIb by RNA degradation by delivering deoxyoligonucleotides
piggybacked with control vivo-morpholinos into zebrafish thrombocytes.
AB - Morpholino and vivo-morpholino gene knockdown methods have been used to study
thrombocyte function in zebrafish. However, a large-scale knockdown of the entire
zebrafish genome using these technologies to study thrombocyte function is
prohibitively expensive. We have developed an inexpensive gene knockdown method,
which uses a hybrid of a control vivo-morpholino and a standard antisense
oligonucleotide specific for a gene. This hybrid molecule is able to deliver
antisense deoxyoligonucleotides into zebrafish thrombocytes because it piggybacks
on a control vivo-morpholino. To validate use of this hybrid molecule in gene
knockdowns, we targeted the thrombocyte specific alphaIIb gene with a hybrid of a
control vivo-morpholino and an oligonucleotide antisense to alphaIIb mRNA. The
use of this piggyback technology resulted in degradation of alphaIIb mRNA and led
to thrombocyte functional defect. This piggyback method to knockdown genes is
inexpensive since one control vivo-morpholino can be used to target many
different genes by making many independent gene-specific oligonucleotide hybrids.
Thus, this novel piggyback technology can be utilized for cost-effective large
scale knockdowns of genes to study thrombocyte function in zebrafish.
PMID- 25135205
TI - The Concerns About Recurrence Questionnaire: validation of a brief measure of
fear of cancer recurrence amongst Danish and Australian breast cancer survivors.
AB - PURPOSE: Fear of cancer recurrence (FCR) is prevalent amongst survivors, and
breast cancer survivors are particularly vulnerable. Currently, there are few
well-validated brief measures of FCR and none specific to breast cancer. This
manuscript describes the development and initial validation of a new measure of
FCR for breast cancer survivors, the Concerns about Recurrence Questionnaire
(CARQ), and reports its initial validation in an Australian and Danish population
based sample of breast cancer survivors. METHODS: CTT analyses explored scale
reliability and validity; Rasch analyses explored model fit statistics, item bias
(DIF) and local dependency. Three-item, four-item and five-item versions were
considered. RESULTS: Two hundred eighteen Australian women aged 28-45 years
diagnosed with early-stage breast cancer (stages 0-2) and 2001 Danish women
diagnosed with breast cancer (stages 1-3) aged 26-70 completed the CARQ. Based on
the results of both CTT and IRT analyses, the four-item English version of the
scale performed best. Although the CTT analyses suggested that the CARQ-4 was
reliable and valid in both samples, Rasch analyses identified item bias relative
to age, and local dependence which may be remedied by further scale development.
CONCLUSIONS: The CARQ-4 English version is currently one of the most rigorously
tested brief scales of FCR available. IMPLICATIONS FOR CANCER SURVIVORS: The
availability of more valid and reliable brief measures of FCR will help to
promote research and screening of FCR amongst cancer survivors.
PMID- 25135206
TI - Identifying suicidal symptoms in prostate cancer survivors using brief self
report.
AB - PURPOSE: Prostate cancer (PC) survivors are at elevated risk for completed
suicide even many years post-treatment. Despite this risk, practical and
efficient methods for assessing these symptoms have not been established. We
sought to determine if suicidal symptoms could be effectively and efficiently
identified in a cohort of PC survivors, and whether these men were receptive to
emotional health interventions. METHODS: Six hundred fifty-six PC survivors, an
average of 5 years post-diagnosis, completed eight self-report items about
suicidal symptoms and behavior in the past 7 days, and 12 months, as well as
medical utilization and interest in emotional health support. RESULTS: Between
3.6 and 17.9% of PC survivors endorsed a single suicidal ideation item, and
denied all other ideation. All survivors who endorsed serious suicidal
ideation/behavior also endorsed either passive or active ideation. 58.3% of
survivors denied any suicidal symptoms within the past week, but endorsed it
within the past year. Most survivors had medical provider contact within the past
year and were open to receiving information about emotional health interventions.
CONCLUSIONS: Suicidal ideation in PC survivors cannot be accurately evaluated
using only a one-item screen, or by inquiring within a single time frame.
IMPLICATIONS FOR CANCER SURVIVORS: In both research and clinical settings, the
evaluation for suicidal ideation in PC survivors should utilize multiple
questions, across several time periods. It is possible to skip queries about
serious ideation/behavior if passive or active ideation is denied. Once
identified, medical providers should refer these men to psychosocial providers
who can offer emotional support.
PMID- 25135208
TI - The study of the complexes of nitromedicine with cytochrome c and NO-containing
aqueous dosage form in the wound treatment of rats.
AB - The interaction of cytochrome c with nitromedicines, such as 5-nitrofural, 5
nitroxoline, metronidazole and sodium nitrite which enables the generation of
nitric oxide or nitrosyl complexes in the presence of ascorbic acid or sodium
ascorbate in acid medium has been investigated. The pharmaceutical compositions
containing cytochrome c and nitromedicine complexes as active substances were
studied in the experiments by using rats. It has been shown that positive local
and systemic effects were estimated when NO-containing gel was used at burn
treatment. These positive effects at the local level are due to a sufficient
microcirculation index which indicates intensification of the blood flow in the
microvessels in the injured area. These effects at the systemic level provide
maintenance of the general heart rhythm and gradual recovery of the vegetative
balance which is not observed in the animals of the control group.
PMID- 25135207
TI - Barriers to access and minority ethnic carers' satisfaction with social care
services in the community: a systematic review of qualitative and quantitative
literature.
AB - As populations age, the numbers of carers overall and numbers of carers from
minority ethnic groups in particular are rising. Evidence suggests that carers
from all sections of the community and particularly carers from minority groups
often fail to access care services. This may relate to barriers in accessing
services and service dissatisfaction. The aim of this systematic review was to
identify and summarise minority ethnic carers' perceptions of barriers to
accessing community social care services and their satisfaction with these
services if accessed. The following databases were searched from their start
until July 2013: Social Care Online, Social Policy and Research, Scopus,
PsychINFO, HMIC, ASSIA, MEDLINE, Embase, CINAHL Plus and AMED. Thirteen studies
met the inclusion criteria. Most investigated either barriers to access or
satisfaction levels, although three explored both. Only 4 studies investigated
minority ethnic carers' satisfaction with social care, although 12 studies
reported perceived barriers to accessing services. Few studies compared minority
ethnic carers' perceptions with majority ethnic groups, making it difficult to
identify issues specific to minority groups. Most barriers described were
potentially relevant to all carers, irrespective of ethnic group. They included
attitudinal barriers such as not wanting to involve outsiders or not seeing the
need for services and practical barriers such as low awareness of services and
service availability. Issues specific to minority ethnic groups included language
barriers and concerns about services' cultural or religious appropriateness.
Studies investigating satisfaction with services reported a mixture of
satisfaction and dissatisfaction. Barriers common to all groups should not be
underestimated and a better understanding of the relationship between perceived
barriers to accessing services and dissatisfaction with services is needed before
the experiences of all carers can be improved.
PMID- 25135209
TI - Generation of an rhBMP-2-loaded beta-tricalcium phosphate/hydrogel composite and
evaluation of its efficacy on peri-implant bone formation.
AB - Dental implant insertion on a site with low bone quality or bone defect should be
preceded by a bone graft or artificial bone graft insertion to heal the defect.
We generated a beta-tricalcium phosphate (beta-TCP) and poloxamer 407-based
hydrogel composite and penetration of the beta-TCP/hydrogel composite into the
peri-implant area of bone was evaluated by porous bone block experiments. The
maximum penetration depth for porous bone blocks and dense bone blocks were 524
MUm and 464 MUm, respectively. We report the in-vivo performance of a composite
of beta-TCP/hydrogel composite as a carrier of recombinant human bone
morphogenetic protein (rhBMP-2), implanted into a rabbit tibial defect model.
Three holes drilled into each tibia of eight male rabbits were (1) grafted with
dental implant fixtures; (2) filled with beta-TCP/hydrogel composite (containing
5 MUg of rhBMP-2), followed by grafting of the dental implant fixtures. Four
weeks later, bone-implant contact ratio and peri-implant bone formation were
analyzed by radiography, micro-CT and histology of undecalcified specimens. The
micro-CT results showed a significantly higher level of trabecular thickness and
new bone and peri-implant new bone formation in the experimental treatment
compared to the control treatment. Histomorphometry revealed a significantly
higher bone-implant contact ratio and peri-implant bone formation with the
experimental treatment. The use of beta-TCP/poloxamer 407 hydrogel composite as a
carrier of rhBMP-2 significantly promoted new bone formation around the dental
implant fixture and it also improved the quality of the new bone formed in the
tibial marrow space.
PMID- 25135210
TI - Countertransference before Heimann: an historical exploration.
AB - Received wisdom on the history of countertransference rests on two assumptions:
Freud said little about countertransference, and what he did say focused on its
role as an impediment to analytic work; the emergence in the 1950s of a
conception of countertransference as a crucial beneficial component of
psychoanalysis was revolutionary and innovative. Both assumptions are
questionable. Detailed examination of Freud's public and private discussions of
countertransference reveals that he recognized much of its potential value, as
well as its pitfalls, and suggested that the analyst's contributions should be
based on spontaneous affect, measured out consciously. He was aware of the
problematic nature of countertransference, calling for a paper on
countertransference even while cautioning against its public presentation. His
remarks, particularly in letters, taken together with the work of Ferenczi and
other early contributors, show that the pre-1950s literature on
countertransference prefigured much current debate on the topic.
PMID- 25135211
TI - Erik Erikson and his problematic identity.
AB - In his psychohistorical biographies of Luther and Gandhi, Erik Erikson proposed
that great issues of a particular time and place, as experienced by sensitive and
creative individuals who are working to resolve their inner conflicts within
these contexts, could find solutions that transcend themselves and yield
conceptualizations that transform the world. Although Erikson was able to create
a conceptualization of the adolescent task of establishing a coherent identity,
one that gave voice to the aspirations and frustrations of the rebellious student
movements of the 1960s, he was never able, over his lifetime, to resolve his own
identity issues. Was he Dane or German, American or Scandinavian, Jew or
Christian or both? His lifelong back-and-forths on this struggle are chronicled.
PMID- 25135212
TI - Journal Watch review of Research domain criteria (RDoC): Toward a new
classification framework for research on mental disorders.
PMID- 25135213
TI - Journal Watch review of oxytocin and reduction of social threat hypersensitivity
in women with borderline personality disorder.
PMID- 25135214
TI - Journal Watch review of Patient personality and therapist response: an empirical
investigation.
PMID- 25135215
TI - Transformation of personality: deformation and reformation in confronting death.
PMID- 25135216
TI - Detecting protein-protein interactions based on kinase-mediated growth induction
of mammalian cells.
AB - Detection of protein-protein interactions (PPIs) is important for understanding
numerous processes in mammalian cells; however, existing PPI detection methods
often give significant background signals. Here, we propose a novel PPI-detection
method based on kinase-mediated growth induction of mammalian cells. In this
method, target proteins are fused to the intracellular domain of c-kit (c-kit
ICD) and expressed in interleukin-3-dependent mammalian cells. The PPI induces
dimerization and activation of c-kit ICDs, which leads to cell growth in the
absence of interleukin-3. Using this system, we successfully detected the ligand
dependent homo-interaction of FKBPF36V and hetero-interaction of FKBP and
FRBT2098L, as well as the constitutive interaction between MDM2 and a known
peptide inhibitor. Intriguingly, cells expressing high-affinity peptide chimeras
are selected from the mixture of the cell populations dominantly expressing low
affinity peptide chimeras. These results indicate that this method can detect
PPIs with low background levels and is suitable for peptide inhibitor screening.
PMID- 25135217
TI - Discovery of novel peptides regulating competence development in Streptococcus
mutans.
AB - A MarR-like transcriptional repressor (RcrR) and two predicted ABC efflux pumps
(RcrPQ) encoded by a single operon were recently shown to be dominant regulators
of stress tolerance and development of genetic competence in the oral pathogen
Streptococcus mutans. Here, we focused on polar (DeltarcrR-P) and nonpolar
(DeltarcrR-NP) rcrR mutants, which are hyper- and nontransformable, respectively,
to dissect the mechanisms by which these mutations impact competence. We
discovered two open reading frames (ORFs) in the 3' end of the rcrQ gene that
encode peptides of 27 and 42 amino acids (aa) which are also dramatically
upregulated in the DeltarcrR-NP strain. Deletion of, or start codon mutations in,
the ORFs for the peptides in the DeltarcrR-NP background restored competence and
sensitivity to competence-stimulating peptide (CSP) to levels seen in the
DeltarcrR-P strain. Overexpression of the peptides adversely affected competence
development. Importantly, overexpression of mutant derivatives of the ABC
exporters that lacked the peptides also resulted in impaired competence. FLAG
tagged versions of the peptides could be detected in S. mutans, and FLAG tagging
of the peptides impaired their function. The competence phenotypes associated
with the various mutations, and with overexpression of the peptides and ABC
transporters, were correlated with the levels of ComX protein in cells.
Collectively, these studies revealed multiple novel mechanisms for regulation of
competence development by the components of the rcrRPQ operon. Given their
intimate role in competence and stress tolerance, the rcrRPQ-encoded peptides may
prove to be useful targets for therapeutics to diminish the virulence of S.
mutans.
PMID- 25135218
TI - HilD induces expression of Salmonella pathogenicity island 2 genes by displacing
the global negative regulator H-NS from ssrAB.
AB - Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2) have essential roles
in the pathogenesis of Salmonella enterica. Previously, we reported
transcriptional cross talk between SPI-1 and SPI-2 when the SPI-1 regulator HilD
induces expression of the SsrA/B two-component system, the central positive
regulator of SPI-2, during the growth of Salmonella to late stationary phase in
LB rich medium. Here, we further define the mechanism of the HilD-mediated
expression of ssrAB. Expression analysis of cat transcriptional fusions
containing different regions of ssrAB revealed the presence of negative
regulatory sequences located downstream of the ssrAB promoter. In the absence of
these negative cis elements, ssrAB was expressed in a HilD-independent manner and
was no longer repressed by the global regulator H-NS. Consistently, when the
activity of H-NS was inactivated, the expression of ssrAB also became independent
of HilD. Furthermore, electrophoretic mobility shift assays showed that both HilD
and H-NS bind to the ssrAB region containing the repressing sequences. Moreover,
HilD was able to displace H-NS bound to this region, whereas H-NS did not
displace HilD. Our results support a model indicating that HilD displaces H-NS
from a region downstream of the promoter of ssrAB by binding to sites overlapping
or close to those sites bound by H-NS, which leads to the expression of ssrAB.
Although the role of HilD as an antagonist of H-NS has been reported before for
other genes, this is the first study showing that HilD is able to effectively
displace H-NS from the promoter of one of its target genes.
PMID- 25135219
TI - The biochemical value of urinary metalloproteinases 3 and 9 in diagnosis and
prognosis of bladder cancer in Egypt.
AB - BACKGROUND: Matrix metalloproteinases (MMPs) have long been associated with
cancer-cell invasion and metastasis. Few studies are available that describe this
association with bladder cancer either related or unrelated to schistosoma
infection.Evaluating the urinary levels of MMP3 and MMP9 as diagnostic and
prognostic biomarkers in different stages of schistosomal and non schistosomal
bladder cancer was the aim of the present study.Urine samples were collected from
70 patients with schistosomal and non schistosomal bladder cancer at early and
advanced stages and also from 12 healthy volunteers as controls. Urinary levels
of MMP-3 and MMP-9 was measured by ELISA technique. Sensitivity and specificity
of both markers were determined. RESULTS: Urinary levels of both MMP-3 and MMP-9
were significantly elevated in all bladder cancer patients compared with
controls. MMP-3 started to elevate in early stages of schistosomal bladder cancer
( 0.173 ng/ml) and non-schistosomal bladder cancer patients (0.308 ng/ml)
compared to control (0.016 ng/ml) and remained elevated in advanced stages
(0.166, 0.235 ng/ml) of both types of bladder cancer patients. In contrast, MMP-9
showed a significant elevation in advanced stages only of both schistosomal and
non schistosomal bladder cancer patients (10.33, 21.22 ng/ml) compared to control
(0.409 ng/ml) and this elevation of both markers was much higher in non
schistosomal bladder cancer. Both Metalloproteinases were specific for the
diagnosis of the disease but MMP-3 was more sensitive and this sensitivity was
evident in the early stage (84.85% for MMP3, 27.28% for MMP9). CONCLUSIONS: MMP3
may be the recommended urinary metalloproteinases as early diagnostic biomarker
in the early stages of both types of bladder cancer although both MMP9 and MMP3
can be used in the diagnosis of advanced stages. Further studies are required on
large number of urine samples to confirm these results.
PMID- 25135220
TI - beta6 integrin induces the expression of metalloproteinase-3 and
metalloproteinase-9 in colon cancer cells via ERK-ETS1 pathway.
AB - We previously reported that beta6 integrin played an important role in the
progression of colon cancer. In this study, we demonstrated that beta6 integrin
induced the expression of MMP-3/MMP-9 and the invasion of colon cancer cells.
Moreover, that function was abolished by the inhibition of ERK/MAPK pathways or
knockdown of ETS1, an important transcription factor of MMP genes. Here, we
showed that beta6 induced phosphorylation of ETS1 via the ERK/MAPK pathways,
through which the MMP-3/MMP-9 promoters were stimulated, thereby leading to the
up-regulation of MMP-3/MMP-9, and subsequent the invasion of colon cancer cells.
PMID- 25135221
TI - A novel beta-catenin signaling pathway activated by IL-1beta leads to the onset
of epithelial-mesenchymal transition in breast cancer cells.
AB - Interleukin 1beta has been associated with tumor development, invasiveness and
metastasis in various types of cancer. However, the molecular mechanisms
underlying this association have not been clearly elucidated. The present study
is the first to show, in breast cancer cells, that an IL-1beta/IL-1RI/beta
catenin signaling pathway induces beta-catenin accumulation due to GSK3beta
inactivation by Akt phosphorylation. Translocation to the nucleus of accumulated
beta-catenin and formation of the TCF/Lef/beta-catenin complex induce sequential
expression of c-MYC, CCDN1, SNAIL1 and MMP2, leading to up-regulation of
proliferation, migration and invasion; all of the processes shown to be required,
in cancerous cells, to initiate transition from a non-invading to an invasive
phenotype.
PMID- 25135222
TI - TIP30 nuclear translocation negatively regulates EGF-dependent cyclin D1
transcription in human lung adenocarcinoma.
AB - Aberrant epidermal growth factor (EGF)-dependent signaling plays a key role in
the progression of human carcinomas. We found that TIP30, a tumor suppressor
protein, translocated into the nucleus of human lung adenocarcinoma cells
following EGF treatment, and the selective inhibitors of EGFR signaling pathways
blocked this effect. Chromatin immunoprecipitation assays revealed that TIP30
negatively regulated EGF-dependent transcriptional activation of CCND1 through a
HDAC1-dependent mechanism. In lung adenocarcinoma patients, the level of nuclear
TIP30 was inversely correlated with that of EGFR and cyclin D1. These findings
suggest that nuclear TIP30-induced downregulation of cyclin D1 transcription
antagonizes EGFR signaling and suppresses tumorigenesis.
PMID- 25135223
TI - Strategy to enhance the anticancer efficacy of X-ray radiotherapy in melanoma
cells by platinum complexes, the role of ROS-mediated signaling pathways.
AB - Radiotherapy plays an important role in treatment of cancers with low toxicity to
the surrounding normal tissues. However, it still fails to eradicate hypoxic
tumors due to the occurrence of radioresistance. Therefore, the search for new
radiation sensitizers is of great significance. Platinum (Pt) complexes have been
identified as potential radiation sensitizers to increase the sensitivity of
cancer cells to radiotherapy. In the present study, we have synthesized four Pt
complexes containing (2 - benzimidazole [4, 5-f] - [1, 10] phenanthroline) ligand
and found that they could effectively enhance the X-ray-induced growth inhibition
against A375 human melanoma cells through induction of G2/M cell cycle arrest. In
contrast, they showed much lower cytotoxicity toward human normal cells. The
complexes also dramatically inhibited the TrxR activity and caused intracellular
ROS overproduction, due to the Auger electron effect of heavy metal element under
X-ray radiation. Excessive ROS triggered DNA damage and activated downstream
signaling pathways, including the phosphorylation of p53 and p38MAPK, and down
regulation of phosphorylated AKT and ERK, finally resulted in increase of
radiosensitivity and inhibition of tumor reproduction. Taken together, our
results suggest that the synthetic Pt complexes could be further developed as
sensitizers of X-ray radiotherapy.
PMID- 25135224
TI - Postoperative changes in amniotic membrane as a carrier for allogeneic cultured
limbal epithelial transplantation.
AB - PURPOSE: To investigate the morphologic changes and outcomes of the amniotic
membrane as a carrier for allogeneic cultivated limbal epithelial
transplantation. DESIGN: Prospective, noncomparative, interventional study.
METHODS: A total of 16 eyes receiving allogeneic cultivated limbal epithelial
transplantation with amniotic membrane as a carrier were enrolled. Morphologic
changes in the amniotic membrane were observed by confocal microscopy and RTVue
optical coherence tomography. The paired t test was employed to compare the mean
best corrected visual acuity (BCVA) and corneal stromal thickness. RESULTS: Of
the 16 eyes, 12 had stable ocular surfaces (group A), while the other 4 eyes had
failed surgeries due to immune rejection (group B). Confocal microscopy showed
residual amniotic membrane tissues in 8 eyes in group A at 1 year. However, the
amniotic membrane was not detected in group B at 8-10 months. RTVue optical
coherence tomography showed discontinuous amniotic membrane tissues in all eyes
in group A at 1 year, while highly reflective opacity was seen in the corneal
stroma in group B. There were no statistically significant differences in mean
BCVA and corneal stromal thickness in group A at 1 month and 1 year after
transplantation (P > 0.05), but the mean BCVA showed a statistically significant
difference at 1 month and after the disappearance of the amniotic membrane in
group B (P < 0.05). CONCLUSIONS: For eyes with stable ocular surfaces after
cultivated limbal epithelial transplantation, the amniotic membrane can be
present in the cornea for at least 1 year, with no impact on visual acuity or
corneal stromal thickness. Chronic inflammation and neovascularization on the
ocular surface may accelerate the disappearance of the amniotic membrane.
PMID- 25135225
TI - Recurrent 8q13.2-13.3 microdeletions associated with branchio-oto-renal syndrome
are mediated by human endogenous retroviral (HERV) sequence blocks.
AB - BACKGROUND: Human endogenous retroviral (HERV) sequences are the remnants of
ancient retroviral infection and comprise approximately 8% of the human genome.
The high abundance and interspersed nature of homologous HERV sequences make them
ideal substrates for genomic rearrangements. A role for HERV sequences in
mediating human disease-associated rearrangement has been reported but is likely
currently underappreciated. METHODS AND RESULTS: In the present study, two
independent de novo 8q13.2-13.3 microdeletion events were identified in patients
with clinical features of Branchio-Oto-Renal (BOR) syndrome. Nucleotide-level
mapping demonstrated the identical breakpoints, suggesting a recurrent
microdeletion including multiple genes such as EYA1, SULF1, and SLCO5A1, which is
mediated by HERV1 homologous sequences. CONCLUSIONS: These findings raise the
potential that HERV sequences may more commonly underlie recombination of dosage
sensitive regions associated with recurrent syndromes.
PMID- 25135226
TI - Developing and evaluating interventions that are applicable and relevant to
inpatients and those who care for them; a multiphase, pragmatic action research
approach.
AB - BACKGROUND: Randomised controlled trials may be of limited use to evaluate the
multidisciplinary and multimodal interventions required to effectively treat
complex patients in routine clinical practice; pragmatic action research
approaches may provide a suitable alternative. METHODS: A multiphase, pragmatic,
action research based approach was developed to identify and overcome barriers to
nutritional care in patients admitted to a metropolitan hospital hip-fracture
unit. RESULTS: Four sequential action research cycles built upon baseline data
including 614 acute hip-fracture inpatients and 30 purposefully sampled
clinicians. Reports from Phase I identified barriers to nutrition screening and
assessment. Phase II reported post-fracture protein-energy intakes and intake
barriers. Phase III built on earlier results; an explanatory mixed-methods study
expanded and explored additional barriers and facilitators to nutritional care.
Subsequent changes to routine clinical practice were developed and implemented by
the treating team between Phase III and IV. These were implemented as a new
multidisciplinary, multimodal nutritional model of care. A quasi-experimental
controlled, 'before-and-after' study was then used to compare the new model of
care with an individualised nutritional care model. Engagement of the
multidisciplinary team in a multiphase, pragmatic action research intervention
doubled energy and protein intakes, tripled return home discharge rates, and
effected a 75% reduction in nutritional deterioration during admission in a
reflective cohort of hip-fracture inpatients. CONCLUSIONS: This approach allowed
research to be conducted as part of routine clinical practice, captured a more
representative patient cohort than previously reported studies, and facilitated
exploration of barriers and engagement of the multidisciplinary healthcare
workers to identify and implement practical solutions. This study demonstrates
substantially different findings to those previously reported, and is the first
to demonstrate that multidisciplinary, multimodal nutrition care reduces intake
barriers, delivers a higher proportional increase in protein and energy intake
compared with baseline than other published intervention studies, and improves
patient outcomes when compared with individualised nutrition care. The findings
are considered highly relevant to clinical practice and have high translation
validity. The authors strongly encourage the development of similar study designs
to investigate complex health problems in elderly, multi-morbid patient
populations as a way to evaluate and change clinical practice.
PMID- 25135227
TI - Antenatal hepatitis B in a large teaching NHS Trust - implications for future
care.
AB - OBJECTIVES: To establish the workload expected as a result of introducing
antenatal antivirals for the prevention of vertical transmission of hepatitis B
virus. METHODS: Retrospective review of all HBsAg-positive women and their
infants, between 2005 and 2011, in a large (population 1 million) teaching NHS
Trust in Leicester, UK, a highly ethnically diverse city. RESULTS: 7% of
pregnancies occurred in women who were taking, or would now be recommended to
take, antenatal antivirals. 176 infants were born to 140 HBsAg-positive women
through 172 pregnancies (mean 29 pregnancies/year). Two (1.1%) were vertically
infected, including one born to a mother with HBeAg(-)/HBeAb(+) disease and HBV
viral load 2 million IU/ml who would not currently be recommended for antenatal
antivirals. 81.1% infants completed all HBV vaccinations; 79.5% completed
serology testing. 96.4% women were referred to the hepatitis clinic, but 30%
disengaged from clinic follow-up, with no significant difference between ethnic
groups in terms of maternal disengagement, or failure to complete infant
vaccinations or serology testing. CONCLUSIONS: Only a small percentage of HBsAg
positive women are likely to meet the newly published criteria for antenatal anti
viral treatment. Strengthened community engagement across multiple ethnic groups
is of paramount importance to improve maternal and infant outcomes.
PMID- 25135228
TI - Wishful thinking blurs interpretation of AES data in a high endemic region of
India.
PMID- 25135229
TI - Prevalence, incidence and predictors of anal high-risk HPV infections and
cytological abnormalities in HIV-infected individuals.
AB - OBJECTIVES: Our purpose was to investigate prevalence, incidence and risk factors
of anal high risk-HPV infections and cytological abnormalities in HIV-positive
individuals. METHODS: A cohort of consecutively enrolled HIV-positive patients
underwent, at baseline visit, a sexual behaviors questionnaire, anoscopy, HPV
testing and cytological examination. Hybridization and multiplex-PCR were used
for DNA detection and typing; HPV E6-E7 mRNA expression was analyzed in HR-HPV+
patients. Logistic regression was used to assess predictors of HR-HPV infection
and anal dysplasia. RESULTS: 233 HIV-infected patients were enrolled (81% males,
median age 44 years). HR-HPV was detected in 144 anal swabs and showed a positive
association with CDC stage C and a negative association with a higher CD4 count
and the use of a NNRTI-based antiretroviral regimen. HR-HPV DNA detection and
anal warts at baseline were associated to cytological abnormalities; a detectable
HIV-RNA independently predicted new onset anal dysplasia at follow-up (incidence
15.4 per 100 patients-year). Incidence of new HR-HPV infection was 44.2 per 100
patients-year. CONCLUSIONS: The relevance of screening for anal dysplasia in HIV+
patients is emphasized, especially in those with detectable plasma HIV-RNA, anal
HR-HPV infection or compromised immunological status.
PMID- 25135230
TI - Risk of tuberculosis among healthcare workers in an intermediate-burden country:
a nationwide population study.
AB - OBJECTIVE: The potential association between healthcare workers (HCWs) and the
risk of clinically active tuberculosis (TB) in countries with intermediate TB
burdens remains unclear. METHODS: A nationwide, population-based cohort study was
performed by using Taiwan National Health Insurance Database during 2000-2010. We
included HCWs and non-HCWs without history of tuberculosis matched at a 1:1 ratio
according to age, sex, monthly income, underlying comorbidities, and concomitant
medications. All subjects were followed from the date of enrollment until TB
occurrence, death, or 31 December 2010. RESULTS: The study population comprised
11,811 healthcare workers and 11,811 matched subjects. 62 HCWs and 38 control
subjects developed TB during a median follow-up period of 9.4 years. The
incidence of TB was higher among HCWs than among matched subjects (61.08 vs.
37.81 per 100,000 person-years). The risk of TB was also greater among HCWs
(adjusted hazard ratio [aHR], 1.62; 95% confidence interval [CI], 1.08-2.43),
particularly for pulmonary TB in comparison with extrapulmonary TB (aHR, 1.56;
95% CI, 1.02-2.39). Among different job categories of HCWs, we found that only
nurses had a significantly increased risk of developing TB (aHR, 2.55; 95% CI,
1.37-4.72) compared to the matched cohort. CONCLUSIONS: HCWs are associated
independently with a higher risk of developing TB in this intermediate-burden
country. Therefore, the importance of TB surveillance among HCWs should be
emphasized.
PMID- 25135231
TI - Severe fever with thrombocytopenia syndrome bunyavirus-related human
encephalitis.
AB - BACKGROUND: Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging
infectious disease caused by a novel bunyavirus. Until recently, SFTSV-associated
encephalitis remained largely uninvestigated. METHODS: We made clinical
investigation on SFTS patients who experienced encephalitis in one reference
hospital in Henan Province from 2011 to 2013 to identify the risk factors for
encephalitis occurrence and their fatal outcome development. RESULTS: Altogether
538 SFTS patients were included and 19.1% of them developed encephalitis. Fatal
outcome occurred in 44.7% of the encephalitis patients. The risk factors
associated with encephalitis occurrence and death included older age, longer
delay between disease onset and hospital admission, pre-existing diabetes and
myalgias, as well as the laboratory evaluations of higher virus load on
admission, decreased WBC, PLT count, lymphocyte percentage and ALB, elevated
neutrophils percentage, AST, ALT, LDH, CK, ALP, GGT, BUN and CREA. These
parameters could be used as potential predictors referring to severe SFTS cases.
One SFTSV strain was isolated from cerebrospinal fluid sample. Cytokine/chemokine
assay revealed that blood EOTAXIN, IFN-gamma, IL-15, IL-6, IP-10, TNF-alpha were
remarkably elevated before clinical deterioration in the confirmed encephalitis
patient. CONCLUSIONS: SFTSV is capable of infecting the central nervous system
and screening for SFTSV in encephalitis of unknown reason should be performed in
SFTS endemic regions. The encephalitis occurrence and fatal outcome could be
potentially predicted by clinical and laboratory evaluations.
PMID- 25135232
TI - Renal and visceral protection in thoracoabdominal aortic surgery.
AB - OBJECTIVES: Open thoracoabdominal aortic aneurysm (TAAA) repair traditionally
carries substantial perioperative morbidity and mortality, primarily from distal
aortic ischemia. Advances in surgical techniques, adjuncts, and strategies have
greatly improved outcomes. METHODS: We analyzed outcomes of 1267 open consecutive
TAAA repairs between January 2005 and September 2013. We provided cold
crystalloid renal perfusion whenever the renal ostia were accessible; according
to extent of repair, we selectively used left heart bypass and provided
isothermic blood to the celiac axis and superior mesenteric artery. Repair was
extensive (Crawford extent I and II) in 717 cases (57%). Left heart bypass was
used in 645 (51%) cases, cold crystalloid renal perfusion in 987 (78%), and
isothermic visceral perfusion in 318 (25%). Additional patient-specific surgical
adjuncts included endarterectomy of renal or visceral vessels, open stent
placement within these vessels, or use of both techniques; at least one was used
in 447 repairs (35%). RESULTS: Thirty-day survival was 95% (1198/1267); overall
operative mortality was 8% (104/1267). Acute renal dysfunction occurred in 155
(12%), renal failure requiring hemodialysis at hospital discharge in 84 (7%), and
bowel ischemia in 9 (<1%). Extent II and III TAAA repairs carried the highest
risks of postoperative renal dysfunction and renal failure requiring hemodialysis
at hospital discharge. CONCLUSIONS: Contemporary protective strategies allow open
TAAA repair with substantially fewer renal and visceral ischemic complications.
Although bowel ischemia is uncommon, renal failure remains a concern, especially
in extent II and extent III TAAA repairs. Additional studies are needed to
identify and improve renal protection strategies.
PMID- 25135233
TI - Persistent fenestration may be a marker for physiologic intolerance after Fontan
completion.
AB - BACKGROUND: We sought to evaluate the medium-term implications of fenestration
status. METHODS: Between 1994 and 2012, 326 patients received an extracardiac
Fontan (hospital mortality n = 6, 1.8%). A fenestration was routinely created (n
= 306, 94%) unless there was technical difficulty. Three hundred patients
discharged with an open fenestration were included. The primary end points were
death and Fontan failure. Secondary outcomes were Fontan complications such as
venovenous collaterals, protein-losing enteropathy, pacemaker requirement, and
arrhythmias. RESULTS: The fenestration was closed in 260 patients: 185 as a
catheter intervention (62%) and 75 (25%) spontaneously. Forty patients (13%) had
the fenestration open at a median follow-up period of 5.05 years. Of these
patients, catheter-based closure failed in 10 (3%). There was no statistically
significant difference in pre-Fontan hemodynamic parameters, such as pulmonary
artery pressure and pulmonary vascular resistance between the patients with open
fenestration and the ones with closed fenestration. Patients with an open
fenestration had significantly more late deaths (P < .001), Fontan failure (P =
.021), and Fontan complications (P = .011) compared with those with a closed
fenestration. Multivariable Cox regression revealed open fenestration (P < .001)
and indeterminate ventricular morphology (P = .002) as risk factors for
death/Fontan failure, and ventricular dysfunction (P = .014) and open
fenestration (P = .009) as risk factors for Fontan complications. CONCLUSIONS:
Persistent fenestration was a marker for physiologic intolerance as noted by
increased rates of mortality and a higher incidence of Fontan
failure/complications. The specificity of pre-Fontan physiologic data for
fenestration status may not have the fidelity needed for long-term care and thus,
the consequences of decision making regarding fenestration status may not be
determined until well after the operation.
PMID- 25135234
TI - Surgery of postinfarction ventricular septal rupture: the effect of David infarct
exclusion versus Daggett direct septal closure on early and late outcomes.
AB - OBJECTIVE: David infarct exclusion and Daggett direct septal closure are
alternative techniques to repair postinfarction ventricular septal rupture. The
aim of the present study was to compare the 2 methods with regard to
postoperative morbidity, 30-day mortality, and long-term survival. METHODS: From
May 1981 to December 2010, 110 patients underwent surgery for postinfarction
ventricular septal rupture. Data were collected on the clinical, angiographic,
and echocardiographic findings, operative procedures, early morbidity, and
survival time. The epidemiologic design was of an exposed (David infarct
exclusion, n = 42) versus a nonexposed (Daggett direct closure, n = 68) cohort
with 3 endpoints: postoperative morbidity, 30-day mortality, and long-term
survival. The crude effect of the repair technique versus the endpoint was
estimated using univariate statistics. Stratification analysis using the Mantel
Haenszel method was done to quantify the confounders and pinpoint the effect
modifiers. Adjustment for confounders was performed using logistic regression and
Cox regression analysis, and with propensity score stratification statistics.
Survival curves were analyzed using the Breslow test and log-rank test. RESULTS:
The surgical technique had no influence on postoperative morbidity. The 30-day
mortality was 16.7% in the David group and 48.5% in the Daggett group (P = .000).
Long-term survival was greater after David than after Daggett, with 5- and 10
year survival of 69% versus 38% and 48% versus 27%, respectively (P = .004).
Total coronary revascularization improved survival more in the David than in the
Daggett group. CONCLUSIONS: David infarct exclusion was superior to Daggett
direct septal closure for early and late survival after surgery for
postinfarction ventricular septal rupture. Total coronary revascularization
improved survival more in the David than in the Daggett group.
PMID- 25135235
TI - Acute Risk Change for Cardiothoracic Admissions to Intensive Care (ARCTIC index):
a new measure of quality in cardiac surgery.
AB - BACKGROUND: Quality of cardiac surgical care may vary between institutions.
Mortality is low and large numbers are required to discriminate between
hospitals. Measures other than mortality may provide better comparisons.
OBJECTIVES: To develop and assess the Acute Risk Change for Cardiothoracic
Admissions to Intensive Care (ARCTIC) index, a new performance measure for
cardiothoracic admissions to intensive care units (ICUs). METHODS: The Australian
and New Zealand Society of Cardiac and Thoracic Surgeons database and Australian
and New Zealand Intensive Care Society Adult Patient Database were linked.
Logistic regression was used to generate a predicted risk of death first from
preoperative data using the previously validated Allprocscore and second on
admission to an ICU using Acute Physiology and Chronic Health Evaluation III
score. Change in risk as a percentage (ARCTIC) was calculated for each patient.
The validity of ARCTIC as a marker of quality was assessed by comparison with
intraoperative variables and postoperative morbidity markers. RESULTS: Sixteen
thousand six hundred eighty-seven patients at 21 hospitals from 2008 to 2011 were
matched. An increase in ARCTIC score was associated with prolonged
cardiopulmonary bypass time (P = .001), intraoperative blood product transfusion
(P < .001), reoperation (P < .0001), postoperative renal failure (P < .0001),
prolonged ventilation (P < .0001), and stroke (P = .001). CONCLUSIONS: The ARCTIC
index is associated with known markers of perioperative performance and
postoperative morbidity. It may be used as an overall marker of quality for
cardiac surgery. Further work is required to assess ARCTIC as a method to
discriminate between cardiac surgical units.
PMID- 25135236
TI - Bayesian stopping guidelines for heart valve premarket approval studies.
AB - OBJECTIVES: The Data Monitoring Committee (DMC) for the premarket approval (PMA)
study of a new heart valve prosthesis convenes periodically to review the
accumulating results of the study, and determines, among other things, whether
there is enough concern with safety to stop the study. Their deliberations are
largely subjective, based on their combined experience and expertise, but an
objective aid to evaluating complication rates, usually called a stopping rule,
is desirable. METHODS: The US Food and Drug Administration has designated
objective performance criteria (OPC) for 7 heart valve complications. At the end
of the PMA study, when approximately 800 patient-years have been accumulated, the
complication rates must compare favorably with the OPC. Given the results to date
at an interim review of the data, we use a Bayesian approach to compute the
probability of passing the OPC test by the end of study. RESULTS: We provide a
method that the DMC can use to predict the probability of passing the OPC test
for each complication, and a graphical aid for each number of events, observed at
100 patient-year intervals. CONCLUSIONS: Although the DMC ultimately uses
combined experience and expertise to make the decision to stop a PMA valve study,
we have provided an objective assessment of the probability of the valve
ultimately passing the OPC test to aid in making that decision.
PMID- 25135237
TI - Are preoperative B-type natriuretic peptide levels associated with outcome after
pulmonary artery banding and the double switch operation in patients with
congenitally corrected transposition of the great arteries: a pilot study.
PMID- 25135238
TI - The biomarker TP53 divides patients with neoadjuvantly treated esophageal cancer
into 2 subgroups with markedly different outcomes. A p53 Research Group study.
AB - BACKGROUND: Fluorouracil and cisplatin have been used most frequently as
neoadjuvant therapy for esophageal cancer. Both drugs are believed to act via a
p53-dependent apoptosis pathway. The TP53 gene is frequently mutated in
esophageal cancer. OBJECTIVE: To test the value of TP53 as a biomarker prognosing
outcome in patients with neoadjuvantly treated esophageal cancer. PATIENTS AND
METHODS: The investigation included 36 patients with primary operable esophageal
cancer who were treated neoadjuvantly with cisplatin and fluorouracil. The TP53
genotype was assessed from paraffin-embedded diagnostic tumor biopsies using a
standardized gene-specific TP53 sequencing protocol (mark53 kit; mark53 Ltd,
Vienna, Austria). RESULTS: Mutations in the TP53 gene were present in 50% of
tumors. Two-year overall survival rates were 55.6% in patients with a normal TP53
marker status, compared with 16.7% in those with a mutant TP53 gene. In patients
with normal TP53, neoadjuvant treatment resulted in significant advantages in
terms of tumor-associated survival (P=.0049) and overall survival (P=.0304)
compared with those with mutant TP53. The median tumor-associated survival was
34.2 months for patients with normal TP53, compared with 8.9 months for those
with mutant TP53. The latter had a 3-fold higher risk of dying (hazard ratio,
3.01; 95% confidence interval, 1.359-6.86). CONCLUSIONS: The biomarker TP53
divides esophageal cancer patients into 2 categories with markedly different
outcomes: patients with a normal TP53 marker status may experience notable
benefits from neoadjuvant chemotherapy with cisplatin/fluorouracil, whereas those
with a mutant TP53 marker status appear to be at risk for lack of response.
PMID- 25135240
TI - Historical perspectives of The American Association for Thoracic Surgery: David
C. Sabiston, Jr (1924-2009).
PMID- 25135239
TI - Reoperative "valve-in-valve" transapical transcatheter mitral valve replacement
in a high-risk patient with a recent transapical transcatheter aortic valve
replacement and a degenerated bioprosthetic mitral valve.
PMID- 25135241
TI - Historical perspectives of The American Association for Thoracic Surgery: Keith
Reemtsma (1925-2000).
PMID- 25135243
TI - A novel methyltransferase from the intracellular pathogen Plasmodiophora
brassicae methylates salicylic acid.
AB - The obligate biotrophic pathogen Plasmodiophora brassicae causes clubroot disease
in Arabidopsis thaliana, which is characterized by large root galls. Salicylic
acid (SA) production is a defence response in plants, and its methyl ester is
involved in systemic signalling. Plasmodiophora brassicae seems to suppress plant
defence reactions, but information on how this is achieved is scarce. Here, we
profile the changes in SA metabolism during Arabidopsis clubroot disease. The
accumulation of SA and the emission of methylated SA (methyl salicylate, MeSA)
were observed in P. brassicae-infected Arabidopsis 28 days after inoculation.
There is evidence that MeSA is transported from infected roots to the upper
plant. Analysis of the mutant Atbsmt1, deficient in the methylation of SA,
indicated that the Arabidopsis SA methyltransferase was not responsible for
alterations in clubroot symptoms. We found that P. brassicae possesses a
methyltransferase (PbBSMT) with homology to plant methyltransferases. The PbBSMT
gene is maximally transcribed when SA production is highest. By heterologous
expression and enzymatic analyses, we showed that PbBSMT can methylate SA,
benzoic and anthranilic acids.
PMID- 25135242
TI - Prevalence, pattern and perceptions of cleft lip and cleft palate among children
born in two hospitals in Kisoro District, Uganda.
AB - BACKGROUND: Cleft lip with or without cleft palate is one of the most common
congenital anomalies that affect the oro-facial region. The aim of the study was
to determine the period prevalence, pattern and perceptions of cleft lip and
cleft palate in children born between 2005 and 2010 in two hospitals in Kisoro
District, Uganda. METHODS: The study involved a retrospective review of medical
records of mothers who delivered live babies between January 2005 and December
2010 in Kisoro Hospital and St. Francis Hospital, Mutolere in Kisoro District.
Key informant interviews of mothers (n = 20) of the children with cleft lip
and/or clip palate and selected medical staff (n = 24) of the two hospitals were
carried out. The data were analysed using descriptive statistics. RESULTS: Over
the 6 year period, 25,985 mothers delivered live babies in Kisoro Hospital (n =
13,199) and St. Francis Hospital, Mutolere (n = 12,786) with 20 babies having oro
facial clefts. The overall period prevalence of the clefts was 0.77/1,000 live
births. Sixty percent (n = 12) of children had combined cleft lip and palate and
the same proportion had clefts on the left side of the face. More boys were
affected than girls: 13 versus 7. About 45% of mothers were hurt on realizing
that they had delivered a child with an oro-facial cleft. Forty percent of
mothers indicated that a child with oro-facial cleft was regarded as an outcast.
About 91.7% (n = 22) of the medical staff reported that these children were not
accepted in their communities. Surgical intervention and psychosocial support
were the management modalities advocated for by most respondents.
CONCLUSION/RECOMMENDATIONS: The period prevalence of combined cleft lip and
palate in two hospitals in Kisoro District was comparable to some findings
elsewhere. Cleft lip and cleft palate are a medical and psychosocial problem in
Kisoro District that calls for sensitization and counseling of the families and
communities of the affected children. The policy makers need to strategically
plan for provision of rehabilitation with feeding obturators to facilitate easy
feeding to gain weight before surgical intervention of the affected children.
PMID- 25135244
TI - Intratympanic gentamicin treatment for Meniere's disease: a randomized, double
blind, placebo-controlled trial on dose efficacy - results of a prematurely ended
study.
AB - BACKGROUND: Gentamicin is used as a therapeutic agent for Meniere's disease
because of its vestibulotoxicity causing chemo-ablation of the vestibular sensory
epithelia. Its use has increased in recent years. However, there is still no
consensus about the dose regimen of gentamicin in the treatment of Meniere's
disease. In this study two different dose regimen treatment protocols are
compared in a placebo controlled study design. The primary objective is to
quantify the treatment effect on dizziness, the secondary objective is hearing
evaluation. METHODS: We performed a randomized, double-blind, placebo-controlled
study in adults with unilateral Meniere's disease according to the AAO-HNS
guidelines resistant to conservative medication. Three groups received four
injections, administered weekly (four intratympanic injections with 40 mg/mL
gentamicin solution, two injections gentamicin solution and two injections of
placebo in random order, or four injections with placebo). Outcome measures were
the score on the Dizziness Handicap Inventory and pure tone audiometry (PTA).
Intended follow-up was 2 years. RESULTS: During follow-up one patient exceeded
the accepted amount of hearing loss. Further, enrollment was very slow (until 12
months between two patients) and new insights showed an apparent benefit of
intratympanic gentamicin treatment (ITG). Therefore we performed an unscheduled
interim analysis which showed that PTA threshold shifts reached the stopping
criteria in two more patients. Because of this, this study was ended. Of the
three patients with the significant PTA threshold shift two were enrolled in the
gentamicin group. CONCLUSION: No conclusions can be drawn concerning doses
regimens. Now that new publications have shown that ITG treatment can be an
effective and safe treatment, a placebo-controlled randomized controlled trial
may not pass the ethical committee because of these recent reports in literature.
Still, a dose regimen study (without placebo) on ITG treatment needs to be
performed. TRIAL REGISTRATION: This trial was registered in The University
Medical Center Utrecht/ Gelre hospital Apeldoorn. Protocol ID: 07/343, EudraCT
number 2006-005913-37.
PMID- 25135246
TI - Does aerobic exercise mitigate the effects of cigarette smoking on arterial
stiffness?
AB - The largest percentage of mortality from tobacco smoking is cardiovascular
related. It is not known whether regular participation in exercise mitigates the
adverse influence of smoking on vasculature. Accordingly, the authors determined
whether regular aerobic exercise is associated with reduced arterial stiffness in
men who smoke cigarettes. Using a cross-sectional study design, 78 young men were
studied, including sedentary nonsmokers (n=20), sedentary smokers (n=12),
physically active nonsmokers (n=21), and physically active smokers (n=25).
Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV).
There were no group differences in height, body fat, and systolic and diastolic
blood pressure. As expected, both physically active groups demonstrated greater
maximal oxygen consumption and lower heart rate at rest than their sedentary
peers. The sedentary smokers demonstrated greater baPWV than the sedentary
nonsmokers (11.8+/-1 m/s vs 10.6+/-1 m/s, P=.036). baPWV values were not
different between the physically active nonsmokers and the physically active
smokers (10.8+/-1 m/s vs 10.7+/-1 m/s). Chronic smoking is associated with
arterial stiffening in sedentary men but a significant smoking-induced increase
in arterial stiffness was not observed in physically active adults. These results
are consistent with the idea that regular participation in physical activity may
mitigate the adverse effects of smoking on the vasculature.
PMID- 25135245
TI - Open-source electronic data capture system offered increased accuracy and cost
effectiveness compared with paper methods in Africa.
AB - OBJECTIVES: Existing electronic data capture options are often financially
unfeasible in resource-poor settings or difficult to support technically in the
field. To help facilitate large-scale multicenter studies in sub-Saharan Africa,
the African Partnership for Chronic Disease Research (APCDR) has developed an
open-source electronic questionnaire (EQ). STUDY DESIGN AND SETTING: To assess
its relative validity, we compared the EQ against traditional pen-and-paper
methods using 200 randomized interviews conducted in an ongoing type 2 diabetes
case-control study in South Africa. RESULTS: During its 3-month validation, the
EQ had a lower frequency of errors (EQ, 0.17 errors per 100 questions; paper,
0.73 errors per 100 questions; P-value <=0.001), and a lower monetary cost per
correctly entered question, compared with the pen-and-paper method. We found no
marked difference in the average duration of the interview between methods (EQ,
5.4 minutes; paper, 5.6 minutes). CONCLUSION: This validation study suggests that
the EQ may offer increased accuracy, similar interview duration, and increased
cost-effectiveness compared with paper-based data collection methods. The APCDR
EQ software is freely available (https://github.com/apcdr/questionnaire).
PMID- 25135247
TI - Mallet fracture.
PMID- 25135248
TI - The effects of ulnar styloid fractures on patients sustaining distal radius
fractures.
AB - PURPOSE: To determine if ulnar styloid fractures (USF) affect clinical outcome
following distal radius fracture (DRF) in adults under 65 years of age. METHODS:
This study involved 312 patients (aged 18-64) with surgically and nonsurgically
treated DRFs. Patients were followed prospectively at baseline and 3, 6, and 12
months. The primary outcome was the Patient-Rated Wrist Evaluation (PRWE), and
secondary outcomes were range of motion and grip strength. The USFs were
classified by location (tip, middle, and base) and union status. RESULTS: There
were 170 patients with isolated DRFs and 142 with associated USF (64 tip, 32
middle, and 46 base fractures). The mean age of the entire cohort was 48 years
with 218 (70%) women. All USFs were treated nonoperatively. There was a trend of
higher PRWE scores in DRFs associated with USFs compared to isolated DRFs
throughout the study. Associated ulnar styloid base fractures had higher but
clinically insignificant PRWE scores than isolated DRFs at 6 and 12 months.
Patients with an associated USF had a slower recovery of wrist flexion and grip
strength compared to isolated DRF, but values were comparable at 12 months.
United USFs and nonunited USFs had similar PRWE scores at all time points.
CONCLUSIONS: Adults under 65 years old with DRFs and associated USFs initially
have greater pain and disability than those with isolated DRFs; however, this
difference dissipated over time and was not significant at one year. No long-term
differences in measured impairments were observed, but the presence of an
associated USF resulted in a slower recovery of grip strength and wrist flexion.
Presence of a USF nonunion did not significantly affect outcomes. TYPE OF
STUDY/LEVEL OF EVIDENCE: Prognostic II.
PMID- 25135249
TI - Evaluation of the PROMIS physical function computer adaptive test in the upper
extremity.
AB - PURPOSE: To compare psychometric and responder burden characteristics between the
Patient-Reported Outcomes Measurement Information System Physical Function
Computer Adaptive Test (PF CAT) and the Disabilities of Arm, Shoulder, and Hand
(DASH) instruments in a tertiary hand and upper extremity practice. METHODS:
Adult patients who presented to the clinic of 2 hand and upper extremity surgeons
in a university-based tertiary care center were enrolled in this study.
Participants received the DASH and PF CAT administered via tablet computer. Time
to completion was recorded for both the DASH and PF CAT. We conducted statistical
analyses to calculate Pearson correlation coefficients between the 2 instruments
and performed a Rasch item response theory analysis to determine dimensionality,
reliability, ceiling and floor effects, and item bias for each instrument.
RESULTS: A total of 134 patients were included. Time to completion for the DASH
was 262 seconds, and for the PF CAT 57 seconds. The instruments had strong
correlation (r = 0.726). The item and Pearson reliability were 0.97 and 0.94,
respectively, for the DASH and 0.99 and 0.96 for the PF CAT. The DASH and PF CAT
had 5% and 5% of unexplained variance, respectively. The DASH exhibited 5% of
ceiling effect and 1% floor effect whereas the PF CAT had no ceiling or floor
effects. CONCLUSIONS: The psychometric characteristics of the Patient-Reported
Outcomes Measurement Information System PF CAT instrument compared favorably with
the DASH in a tertiary upper extremity practice. Patient time burden was
significantly reduced with the PF CAT compared with the DASH. TYPE OF STUDY/LEVEL
OF EVIDENCE: Diagnostic III.
PMID- 25135251
TI - Pediatric supracondylar humerus fractures.
PMID- 25135250
TI - Selection of tendon grafts for distal radioulnar ligament reconstruction and
report of a modified technique.
AB - PURPOSE: To investigate the graft length necessary to complete a distal
radioulnar ligament reconstruction and assess the suitability of several tendon
graft sources. METHODS: We measured the graft length needed to complete the
distal radioulnar ligament reconstruction in 7 fresh-frozen cadaver specimens.
The pure tendon lengths of 7 tendon graft sources were measured: palmaris longus,
extensor indicis proprius, slips of extensor digiti minimi and abductor pollicis
longus, and portions of flexor carpi ulnaris, flexor carpi radialis, and extensor
carpi ulnaris. A modified technique that allows for a shorter length of graft is
also described, and the suitability of each graft source for this technique was
assessed. RESULTS: The mean graft lengths needed to complete the original and
modified reconstructions were 138 mm and 89 mm, respectively. The average length
of the tendon graft when measured as pure tendon was: palmaris longus (127 mm),
slip of extensor digiti minimi (112 mm), extensor indicis proprius (100 mm),
partial flexor carpi radialis (87 mm), slip of abductor pollicis longus (69 mm),
partial flexor carpi ulnaris (67 mm), and partial extensor carpi ulnaris (67 mm).
The palmaris longus was too short for the original technique in the majority of
specimens but was sufficient to complete the modified technique in every specimen
that had a palmaris longus. Six specimens also had an extensor indicis proprius
of suitable length for the modified technique. CONCLUSIONS: The length of donor
graft required for the modified reconstruction was significantly less than that
needed for the original reconstruction. Three specimens had no donor tendons
sufficiently long to complete the original technique if a pure tendon graft were
used, whereas the modified technique could be completed in all specimens.
CLINICAL RELEVANCE: Many tendon graft sources in the upper extremity are of
insufficient length to complete the distal radioulnar ligament reconstruction as
described. A modified technique using suture anchors may be a useful alternative
in such cases.
PMID- 25135252
TI - Disease-modifying effects of TD-198946 on progressed osteoarthritis in a mouse
model.
PMID- 25135255
TI - Faculty development for clinical teachers in dental education.
AB - Dental education has been reviewed, and suggestions for further enhancement
include the implementation of faculty development activities to enhance teaching
and learning environments. PURPOSE: The aim of this study was to gain insight
into the participants' perceptions of outcomes of faculty development for
clinical teachers and clinical learning environments as well as into the
sustainability of such outcomes. METHODS: The program was organized in the form
of (i) a 2-day seminar; (ii) collegial supervision and development projects; and
(iii) a 1-day follow-up seminar. The participants' perceptions from the five
first programs were studied. A Web-based questionnaire was sent to all
participants, that is 3-27 months after completion of the program (follow-up
survey). RESULTS: The outcomes of the program (response rate 70%) indicate a
strong impact of the program on the clinical teachers' competence and on the
clinical learning environments. The teachers report that they think more about
what their students really learn, have become more conscious about how they
supervise and have been stimulated to become better teachers. The learning
environment as well as collaboration, and calibration between teachers have
improved. The novice teachers report greater benefits than do the experienced
teachers. The participants initiated a variety of development projects during the
program. The majority of the participants continued the development activities.
CONCLUSIONS: The faculty development program presented confirms that faculty
development activities for clinical teachers based on theories of learning and
experiences documented in the literature can be implemented with positive
outcomes for individual teachers and for the learning environments.
PMID- 25135253
TI - A homeostatic function of CXCR2 signalling in articular cartilage.
AB - OBJECTIVE: ELR+ CXC chemokines are heparin-binding cytokines signalling through
the CXCR1 and CXCR2 receptors. ELR+ CXC chemokines have been associated with
inflammatory arthritis due to their capacity to attract inflammatory cells. Here,
we describe an unsuspected physiological function of these molecules in articular
cartilage homeostasis. METHODS: Chemokine receptors and ligands were detected by
immunohistochemistry, western blotting and RT-PCR. Osteoarthritis was induced in
wild-type and CXCR2(-/-) mice by destabilisation of the medial meniscus (DMM).
CXCR1/2 signalling was inhibited in vitro using blocking antibodies or siRNA.
Chondrocyte phenotype was analysed using Alcian blue staining, RT-PCR and western
blotting. AKT phosphorylation and SOX9 expression were upregulated using
constitutively active AKT or SOX9 plasmids. Apoptosis was detected by terminal
deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. RESULTS:
CXCL6 was expressed in healthy cartilage and was retained through binding to
heparan sulfate proteoglycans. CXCR2(-/-) mice developed more severe
osteoarthritis than wild types following DMM, with increased chondrocyte
apoptosis. Disruption of CXCR1/2 in human and CXCR2 signalling in mouse
chondrocytes led to a decrease in extracellular matrix production, reduced
expression of chondrocyte differentiation markers and increased chondrocyte
apoptosis. CXCR2-dependent chondrocyte homeostasis was mediated by AKT signalling
since forced expression of constitutively active AKT rescued the expression of
phenotypic markers and the apoptosis induced by CXCR2 blockade. CONCLUSIONS: Our
study demonstrates an important physiological role for CXCR1/2 signalling in
maintaining cartilage homeostasis and suggests that the loss of ELR+ CXC
chemokines during cartilage breakdown in osteoarthritis contributes to the
characteristic loss of chondrocyte phenotypic stability.
PMID- 25135254
TI - NLRP3 and ASC suppress lupus-like autoimmunity by driving the immunosuppressive
effects of TGF-beta receptor signalling.
AB - OBJECTIVES: The NLRP3/ASC inflammasome drives host defence and autoinflammatory
disorders by activating caspase-1 to trigger the secretion of mature interleukin
(IL)-1beta/IL-18, but its potential role in autoimmunity is speculative. METHODS:
We generated and phenotyped Nlrp3-deficient, Asc-deficient, Il-1r-deficient and
Il-18-deficient C57BL/6-lpr/lpr mice, the latter being a mild model of
spontaneous lupus-like autoimmunity. RESULTS: While lack of IL-1R or IL-18 did
not affect the C57BL/6-lpr/lpr phenotype, lack of NLRP3 or ASC triggered massive
lymphoproliferation, lung T cell infiltrates and severe proliferative lupus
nephritis within 6 months, which were all absent in age-matched C57BL/6-lpr/lpr
controls. Lack of NLRP3 or ASC increased dendritic cell and macrophage
activation, the expression of numerous proinflammatory mediators, lymphocyte
necrosis and the expansion of most T cell and B cell subsets. In contrast, plasma
cells and autoantibody production were hardly affected. This unexpected
immunosuppressive effect of NLRP3 and ASC may relate to their known role in
SMAD2/3 phosphorylation during tumour growth factor (TGF)-beta receptor
signalling, for example, Nlrp3-deficiency and Asc-deficiency significantly
suppressed the expression of numerous TGF-beta target genes in C57BL/6-lpr/lpr
mice and partially recapitulated the known autoimmune phenotype of Tgf-beta1
deficient mice. CONCLUSIONS: These data identify a novel non-canonical
immunoregulatory function of NLRP3 and ASC in autoimmunity.
PMID- 25135256
TI - Implementation of clinical governance in hospitals: challenges and the keys for
success.
AB - There is a number of models and strategies for improving the quality of care such
as total quality management, continuous quality improvement and clinical
governance. The policy of clinical governance is part of the governments overall
strategy for monitoring, assuring and improving in the national health services
organization. Clinical governance has been introduced as a bridge between
managerial and clinical approaches to quality. For successful implementing of
clinical governance, it is necessary to pay attention to firm foundations of the
structure, including equipment, staffing arrangement, supporting specialties, and
staff training. Therefore, as clinical governance improves safety and quality in
health care services, the current situation in hospitals should be evaluated
before any intervention while barriers and blocks on structure and process should
be determined to select a method for changing them. Considering these points
could guarantee success in implementation of clinical governance; otherwise there
would be a little chance to achieve the desired results despite consumption of
plenty of time and huge paper works.
PMID- 25135257
TI - Melatonin improve the sperm quality in forced swimming test induced oxidative
stress in nandrolone treated Wistar rats.
AB - This study investigates the effects of melatonin on the sperm quality and testis
weight after the combination of swimming exercise and nandrolone decanoate
(DECA). Two groups of male Wistar rats were treated for eight weeks as follows;
group A consist of CO (control), Sham, N (DECA), S (swimming) and NS (DECA plus
swimming); and group B: Sham M (sham melatonin), M (melatonin), MN (melatonin
plus DECA), MS (melatonin plus swimming), MNS (melatonin, DECA plus swimming).
The motility of sperm was significantly improved in melatonin groups in
comparison to N, S and NS groups (P<=0.05). The left testes weight was decreased
in N, NS and MNS groups, and the right testes weight was decreased in N,S,NS, MS
and MNS groups in compare with the control group. This study concluded that
melatonin probably could improve the sperm motility and sex organs weight after
the combination of DECA and exercise.
PMID- 25135259
TI - Prevalence and severity of obsessive-compulsive disorder and their relationships
with dermatological diseases.
AB - Most obsessive-compulsive disorder (OCD) patients meet psychiatrists 5 to 10
years after onset of OCD .Its relatively high prevalence ratio and the delay in
seeking help suggest that patients with OCD may seek help at non-psychiatric
clinics. The present study was undertaken to provide some epidemiological data on
the prevalence and severity of OCD in dermatological patients. The participants
included 265 consecutive patients with primary dermatologic chief complaint. They
were visited by a dermatologist and diagnosis of dermatological lesion was done
according to ICD-10. All patients were visited by a psychiatry resident and were
screened for OCD using the structured clinical interview for DSM-IV-TR (SCID-I).
If the diagnosis of OCD has been made, the Yale-Brown obsessive compulsive
scale(Y-BOCS) was used to evaluate the severity of OCD. To analyze the data
student t-test for quantitative variables and X2 tests for categorical variables.
From the total of 265 patients, 24 (9.1%) met the DSM-IV-TR criteria for OCD and
9 (37.5%) with OCD had previously been diagnosed with OCD, however, only three
were treated pharmacologically. The most symptoms were pathological doubt
(29.1%), fear of contamination (29.1%) and washing (54.16%). Severity of OCD
according to Y-BOCS was evaluated among patients with OCD. Six (25%) were found
with subclinical OCD, 11(45.8%) had mild OCD, six (25%) had moderate OCD, and one
(4.2%) was detected with severe OCD. prevalence of OCD in dermatology clinic was
higher compared with general population.
PMID- 25135258
TI - The relationship between anthropometric parameters and bone mineral density in an
Iranian referral population.
AB - Osteoporosis is a common health concern in both developed and developing
countries. In this study the association between anthropometric measures and
osteoporosis was investigated in 3630 males and females visiting BMD clinic of
Shariati Hospital, Tehran, Iran, a teaching hospital and referral center for
osteoporosis affiliated to the Tehran University of Medical Sciences.
Anthropometric measurements obtained and also Bone Mineral Density (BMD)
measurement was done using a Lunar DPXMD densitometer. Data were analyzed using
SPSS with Chi-square and ANOVA with post-hoc tests. Results showed that the
weight, BMI and age had the strongest correlation with the BMD values in the
studied people. While age is negatively correlated with BMD in all the studied
people, a positive association was noted between weight, height and BMI and BMD
parameters (P<0.01). It was concluded that certain anthropometric parameters (BMI
and weight) can considerably affect one's risk of developing osteoporosis.
Further research on the effect of these variables on the association of weight
and BMD is needed.
PMID- 25135260
TI - Total serum IgE concentration in patients with psoriasis: a case-control study.
AB - Psoriasis is a chronic relapsing disorder that involves the skin, nails and
joints. With regard to the role of the immune system in psoriasis, the current
study compared serum IgE concentration in patients with psoriasis with control
group. Current case-control study was conducted in Dermatology clinic of Razi
hospital, Tehran University of medical sciences, Tehran, Iran in 2012. Fifty
eight patients with psoriasis e referred to the clinic were assigned as patient
group and 58 healthy subjects with matched age and sex as a control group.
Patient's history, family history and demographic characteristics such as age and
sex, duration and severity of disease using PASI, were collected and entered into
a form. Consent form was obtained from participants. Serum IgE concentrations of
both study groups were measured by electrochemiluminescence assay in the
laboratory A total number of 58 patients with psoriasis, mean age of 44.15 (19-76
years) and 58 controls with matched age and sex were studied. Mean average of
serum IgE concentration in the control group was 115.13 versus 200/06
concentration in patients group (P=0.16). Serum IgE concentration in 22.4% of
patients versus 17.2% in controls was greater than normal concentration (P=0.48).
No significant correlation was between serum IgE concentration and disease
severity using PASI (P=0.11, r=0.21), neither a significant correlation with
disease duration, age and gender. According to the present study, serum IgE
concentrations are not greater in patients with psoriasis. IgE concentration is
also not associated with the severity of psoriasis based on the PASI score,
therefore, the role of IgE in psoriasis can be considered insignificant as some
previous studies indicate.
PMID- 25135261
TI - Rapid screening of diabetic polyneuropathy: selection of accurate symptoms and
signs in an outpatient clinical setting.
AB - Clinical assessment of distal symmetric polyneuropathy (DPN) involves the
evaluation of symptoms and signs. Although there are numerous tools to evaluate
DPN, there is still a need to determine the most sensitive, specific, and
accurate tests to detect DPN in a busy outpatient clinical setting. A total of
107 patients with type 2 diabetes were examined using Michigan Neuropathy
Screening Instrument (MNSI). Total score of the instrument was used as a standard
to calculate sensitivity, specificity and diagnostic accuracy of every single
item of MNSI to find the most accurate and applicable test for evaluation of DPN.
In patients' history, the most sensitive (99.4%) and accurate (78%) symptoms were
muscle cramp and weakness. Numbness and prickling had lower sensitivity (72.6%
and 67.9%, respectively) but greater specificity (65.2% and 47.8%). In physical
assessment, the most accurate signs were appearance of feet (81.3%), ankle
reflexes (67.2%), and vibration perception (63.5%). Monofilament test had a
sensitivity of 16.7%, accuracy of 31.7% with specificity of 87%. Findings show
that symptoms such as a muscle cramp, weakness, numbness, and prickling, as well
as signs such as ankle reflexes, appearance of feet, and vibration could be used
as the most accurate tests for rapid diagnosis of DPN. In addition, the results
suggest that monofilament examination may not be the optimum test to detect high
risk patients.
PMID- 25135262
TI - Comparison of fumaric acid 5% cream versus triamcinolone 0.1% cream in the
treatment of hand eczema.
AB - Hand eczema is a common distressing skin problem. It is an immune reaction to
haptens. Thus, substances that inhibit Immune system can be effective in the
treatment of hand eczema. In this study, topical fumaric acid 5% cream is
compared with topical steroid in the treatment of hand eczema. Patients with hand
eczema were randomly divided into two groups. One group received fumaric acid 5%
in a cream base, and the other received triamcinolone 0.1% in the same cream
base. Both groups used creams twice daily for one month. Patients were checked
for erythema, excoriation, population and lichenification, EASI score, and
pruritus before and after treatment. In both groups, the mean of all signs of the
disease and EASI score decreased after one month of treatment. There was no
significant difference between the two treatments in decreasing erythema, but
excoriation, population, lichenification, EASI score and itching were all
decreased more in triamcinolone 0.1 % group. Although fumaric acid can inhibit
the immune system; it was less effective for the treatment of all signs of hand
eczema except erythema in comparison to triamcinolone. These results may be
justified for two reasons: low penetration of topical fumaric acid through the
skin or a low concentration used in this study.
PMID- 25135263
TI - An assessment of readiness for pre-implementation of electronic health record in
Iran: a practical approach to implementation in general and teaching hospitals.
AB - Readiness assessment provides a proper image of the existing conditions and an
explanation of facilitated operational plans and functional approaches to
successful implementation of electronic health record. Readiness assessment
requires indices adjusted to particular conditions in each country. Therefore,
the present study attempts to provide an acceptable model in Iran and to provide
an assessment of public and teaching hospitals in medical education university.
After reviewing related papers and descriptive study of five selected countries,
the initial model was designed in the form of a questionnaire for analysis
through Delphi and distributed among 30 experts nationwide. Along identification
of components in the proposed method, a 7-point Likert scale was used to
determine priority of each component. Then, all general -education hospitals at
Tehran University of Medical Education were examined based on this model in terms
of total, relative, or no readiness. The final model was designed in five
dimensions: cultural, leadership and management, technical infrastructure,
governance and operational dimensions; Educational Hospitals were evaluated in
this dimension. 28.6 % of general--teaching hospitals are ready for pre
implementation. It seems to establish uniform strategic and executive team in
Health center is essential for the preparation them in abovementioned area in the
least possible time.
PMID- 25135264
TI - Results of nasolacrimal duct probing in children between 9-48 months.
AB - Congenital nasolacrimal duct obstruction (CNLDO) is a common disease in children.
The classic treatment of CNLDO is probing that was done around one year old.
However, controversy exists regarding the outcome of probing in children older
than one year. This study aimed to find the cure rate of initial probing for
CNLDO and identify factors producing the failure rate in old age. In this
retrospective interventional case series study, 100 eyes of 92 patients aged 9-48
months with CNLDO underwent probing with general anesthesia. According to the
intraoperative results of probing, CNLDO were categorized in two groups of
membranous obstruction at the end of nasolacrimal duct obstruction (NLD) and
complex obstruction at canaliculus, lacrimal sac and N LD. Patients were
categorized in three groups according to the age of probing into under 12, 12 to
24 and over 24 months. Success rate was defined as successful irrigation of NLD
intraoperatively and absence of lacrimation and discharge at 1 week, one, three
and six months postoperatively. The average age of patients and probing were
47.35+/-25.59 and 17.32+/-7.85 months respectively. Membranous obstruction
accounted for 72% of patients and remainder had complex type. An overall cure
rate of 91%, 89% and 60% was found in patients aged 9-12, 12-24 and 24-48 months
respectively. Surgery success rate after six months was 91% in membranous group
and 52% in complex group. There was a significant relation between the type of
obstruction and opening of NLD (p<0.O01). This study showed that the probing
failure of probing after one year was related to the complexity of obstruction
rather than the age of the patient. It is recommended that probing could safely
be done in under 4 years old.
PMID- 25135265
TI - Frequency of exclusive breastfeeding and its affecting factors in Tehran, 2011.
AB - This study was designed to assess the frequency of exclusive breastfeeding in two
health centers of Shahid Beheshti University of Medical sciences in Khak Sefid,
Tehran, Iran. A total of 175 mothers, referred for the third dose of their
infants' DPT vaccination program participated in the study by completing a
questionnaire regarding characteristics of their pregnancy, delivery and
exclusive breastfeeding within the first six months of birth. Two-variable
analysis and logistic regression test were applied to evaluate factors
influencing exclusive breastfeeding. Results indicated that the frequency of
exclusive breastfeeding, i.e., breastfeeding within the first six months of birth
without the use of any other food with or without vitamin supplementation, was
31.17% (95% CI=23.77%-38.57%), which means 48 infants of 154<179 days old Among
154 infants (<179 days old) 48 did not have a history of being separated from
their mothers. In logistic regression analysis, the variables which were directly
associated with exclusive breastfeeding, with 0.05 significance level of alpha,
included breastfeeding within the first hour of birth, eight times or more
breastfeeding per day and receiving breastfeeding education during pregnancy.
Variables with a negative association with breastfeeding included lack of breast
milk, presence of a breast problem that could hinder breastfeeding, bottle
feeding, physician or family's advice not to breastfeed and infant's refusal to
breastfeed. Frequency of breastfeeding within the six months of birth is less
than similar frequencies which are obtained by asking about breastfeeding on the
day of the interview. It is recommended to apply real frequency for assessment,
evaluation and programming of exclusive breastfeeding during the first six months
of birth.
PMID- 25135267
TI - Guyon's tunnel syndrome during pregnancy with concomitant anomalous arch of the
ulnar nerve: a case report.
AB - Numerous causes are reported for ulnar nerve compression at the wrist, known as
Guyon's tunnel syndrome. In the present article, a patient with Guyon's tunnel
syndrome during pregnancy concomitant with an anomaly of ulnar nerve is
described. A 29-year-old Iranian woman presented with clinical features of
Guyon's tunnel syndrome (pain and paresthesia in the fifth finger of the left
hand and atrophy of the first dorsal interosseus muscle). Symptoms of the patient
appeared during the third trimester of pregnancy. Electro diagnostic studies
confirmed Guyon's tunnel syndrome. Surgical exploration revealed an anomalous
arch of the ulnar nerve passing through the flexor carpi ulnaris (FCU) tendon.
The anomalous arch of the ulnar nerve was released by resection of the segment of
FCU tendon passing through the ulnar nerve arch. Therefore, in patients with
Guyon's tunnel syndrome, the ulnar nerve anomaly should be kept in mind as a
cause. Moreover, pregnancy may have a provocative effect on Guyon's tunnel
syndrome similar to carpal tunnel syndrome (CTS).
PMID- 25135266
TI - Effect of repetitive feedback on residents' communication skills improvement.
AB - To evaluate the effect of frequent feedback on residents' communication skills as
measured by a standardized checklist. Five medical students were recruited in
order to assess twelve emergency medicine residents' communication skills during
a one-year period. Students employed a modified checklist based on Calgary
Cambridge observation guide. The checklist was designed by faculty members of
Tehran University of Medical Science, used for assessment of students'
communication skills. 24 items from 71 items of observational guide were
selected, considering study setting and objects. Every two months an expert
faculty, based on descriptive results of observation, gave structured feedback to
each resident during a 15-minute private session. Total mean score for baseline
observation standing at 20.58 was increased significantly to 28.75 after
feedbacks. Results markedly improved on "gathering information" (T1=5.5, T6=8.33,
P=0.001), "building relationship" (T1=1.5, T6=4.25, P<0.001) and "closing the
session" (T1=0.75, T6=2.5, P=0.001) and it mildly dropped on "understanding
patients view" (T1=3, T6=2.33, P=0.007) and "providing structure" (T1=4.17,
T6=4.00, P=0.034). Changes in result of "initiating the session" and "explanation
and planning" dimensions are not statically significant (P=0.159, P=0.415
respectively). Frequent feedback provided by faculty member can improve
residents' communication skills. Feedback can affect communication skills
educational programs, and it can be more effective if it is combined with other
educational methods.
PMID- 25135268
TI - Successful airway management in a patient with tracheal stenosis and
tracheoesophageal fistula: a case report.
AB - A twenty-year-old girl was referred with tracheal stenosis (TS) which was a
consequence of prolonged intubation after head injury because of previous car
accident. The patient was aphasic and had normal respiration. Fiberoptic
bronchoscopy showed complete tracheal obstruction at second tracheal ring level.
Distal trachea was normal through tracheostomy tube. Removal of the tracheostomy
tube and blind reinsertion with a new one was complicated with hypoxia and
respiratory distress. Fibrotic bronchoscopy revealed large tracheoesophageal
fistula (TEF) below tracheal obstruction. Reinsertion of the tracheostomy tube by
fiber optic bronchoscope was successful. Multidetector CT scan was performed on
the same day with confirmation of TS combined with TEF. Surgery was performed on
the next day. No clinical evidence of TEF was found in back history. Inadequate
evaluation of the whole length of the trachea during the first bronchoscopy was
the reasons for missing TEF. TEF should be considered in patients with TS in
spite of no typical symptom such as food aspiration or pulmonary infections.
PMID- 25135269
TI - Cervical sympathetic schwannoma: report of two cases and review of the
literature.
AB - This study describes two cases of cervical sympathetic schwannoma operated at
department of vascular surgery and review the literature to clarify the
demographic, diagnostic, and therapeutic features of these rare lesions for the
first time. Two 32- and 59-year-old ladies both presenting with a painless
cervical mass were referred to our service with the initial diagnosis of carotid
body tumor. At the operation, mobile masses which could be easily dissected from
the surrounding arteries and veins, except for the cervical sympathetic trunk
were observed. Micro-surgical techniques helped us with removing the lesions with
saving the sympathetic trunk in both cases. No permanent deficits were observed
post-operatively in patients. Angiographic studies can provide the only pre
operative clues to diagnose a sympathetic schwannoma. Total removal of the lesion
at the expense of sacrificing the sympathetic nerve is associated with minimal
neurologic deficits which are well tolerated by the patient.
PMID- 25135270
TI - Atypical respiratory distress in a newborn: a diagnostic dilemma.
AB - Neonatal respiratory distress is a very common problem in our practice. The
causes may be respiratory, cardiovascular, central, metabolic, haematological and
surgical. The cause of distress due to transient myocardial depression is not
very common in mild asphyxia. We present a case having transient myocardial
depression with severe respiratory distress and features of shock in a mild
asphyxiated baby.
PMID- 25135271
TI - A case with pachyonychia congenita and B-cell lymphoma.
AB - Pachyonychia congenital (PC) is a rare autosomal dominant genodermatosis
characterized hyperkeratosis affecting the nails and palmoplantar areas, oral
leukokeratosis, and cystic lesions. A 39-year-old woman with PC type 1 (Jadassohn
Lewandowsky syndrome) and B-cell lymphoma is described. No similar disorders or
parental consanguinity were found in her family. Typical features of PC developed
since her early childhood and the diagnosis of B-cell lymphoma was established
seven years ago, without a clear causal relation between these entities. Despite
inherent limitations of a single case, this report may contribute to PC
understanding.
PMID- 25135275
TI - [General anesthesia for ambulatory surgery : Clinical pharmacological
considerations on the practical approach].
AB - Due to modern surgical and anesthesia techniques, many patients undergoing small
or even medium surgical procedures will recover within minutes and can then be
discharged after a few hours of monitoring. Aside from an optimized surgical
technique, a precise and differentiated anesthesia concept is needed to guarantee
rapid recovery and home readiness. Nowadays, remifentanil-propofol represents the
standard regime in ambulatory anesthesia. The use of alfentanil, desfluran or
sevofluran is also possible whereas other intravenous or inhaled anesthetics or
other opioids are rarely used. If endotracheal intubation is necessary, a reduced
intubating dose of neuromuscular blockers (NMB), such as mivacurium, atracurium
and rocuronium, i.e. 1-1.5-times the 95 % effective dose (ED95) is a good
possibility to accelerate neuromuscular recovery while still having acceptable
intubation conditions. Due to its limitations and contraindications,
succinylcholine is not the first choice but may be used in non-fasting patients
in need of urgent (ambulatory) surgery, e.g. in bleeding women undergoing
dilation and curettage. Even with these reduced dosages monitoring of
neuromuscular recovery is crucial and should be applied to all patients when NMBs
are used. Furthermore, patients should receive a risk-adapted postoperative
nausea and vomiting (PONV) prophylaxis, e.g. with 4 mg dexamethasone and 4 mg
ondansetron. Postdischarge nausea and vomiting (PDNV) should be anticipated by a
new risk score and prophylaxis or treatment should be initiated. For
postoperative pain relief, local or regional anesthesia techniques, such as
infiltration, field or nerve blocks should be applied where possible. In
addition, non-opioid analgesics are the basic treatment while longer-lasting
opioids are only necessary for some patients.
PMID- 25135276
TI - Trends in hospitalizations and outcomes for acute cardiovascular disease and
stroke, 1999-2011.
AB - BACKGROUND: During the past decade, efforts focused intensely on improving the
quality of care for people with, or at risk for, cardiovascular disease and
stroke. We sought to quantify the changes in hospitalization rates and outcomes
during this period. METHODS AND RESULTS: We used national Medicare data to
identify all Fee-for-Service patients >=65 years of age who were hospitalized
with unstable angina, myocardial infarction, heart failure, ischemic stroke, and
all other conditions from 1999 through 2011 (2010 for 1-year mortality). For each
condition, we examined trends in adjusted rates of hospitalization per patient
year and, for each hospitalization, rates of 30-day mortality, 30-day
readmission, and 1-year mortality overall and by demographic subgroups and
regions. Rates of adjusted hospitalization declined for cardiovascular conditions
(38.0% for 2011 compared with 1999 [95% confidence interval (CI), 37.2-38.8] for
myocardial infarction, 83.8% [95% CI, 83.3-84.4] for unstable angina, 30.5% [95%
CI, 29.3-31.6] for heart failure, and 33.6% [95% CI, 32.9-34.4] for ischemic
stroke compared with 10.2% [95% CI, 10.1-10.2] for all other conditions).
Adjusted 30-day mortality rates declined 29.4% (95% CI, 28.1-30.6) for myocardial
infarction, 13.1% (95% CI, 1.1-23.7) for unstable angina, 16.4% (95% CI, 15.1
17.7) for heart failure, and 4.7% (95% CI, 3.0-6.4) for ischemic stroke. There
were also reductions in rates of 1-year mortality and 30-day readmission and
consistency in declines among the demographic subgroups. CONCLUSIONS:
Hospitalizations for acute cardiovascular disease and stroke from 1999 through
2011 declined more rapidly than for other conditions. For these conditions,
mortality and readmission outcomes improved.
PMID- 25135277
TI - The post-translational modification of the Clostridium difficile flagellin
affects motility, cell surface properties and virulence.
AB - Clostridium difficile is a prominent nosocomial pathogen, proliferating and
causing enteric disease in individuals with a compromised gut microflora. We
characterized the post-translational modification of flagellin in C. difficile
630. The structure of the modification was solved by nuclear magnetic resonance
and shown to contain an N-acetylglucosamine substituted with a phosphorylated N
methyl-l-threonine. A reverse genetics approach investigated the function of the
putative four-gene modification locus. All mutants were found to have truncated
glycan structures by LC-MS/MS, taking into account bioinformatic analysis, we
propose that the open reading frame CD0241 encodes a kinase involved in the
transfer of the phosphate to the threonine, the CD0242 protein catalyses the
addition of the phosphothreonine to the N-acetylglucosamine moiety and CD0243
transfers the methyl group to the threonine. Some mutations affected motility and
caused cells to aggregate to each other and abiotic surfaces. Altering the
structure of the flagellin modification impacted on colonization and disease
recurrence in a murine model of infection, showing that alterations in the
surface architecture of C. difficile vegetative cells can play a significant role
in disease. We show that motility is not a requirement for colonization, but that
colonization was compromised when the glycan structure was incomplete.
PMID- 25135279
TI - The adductor ratio: a new tool for joint line reconstruction in revision TKA.
AB - PURPOSE: In this study, the value of the adductor tubercle as landmark for joint
line reconstruction in revision total knee arthroplasty (TKA) was investigated.
METHODS: On 100 calibrated full-leg standing radiographs obtained from healthy
volunteers, distances from the medial epicondyle, the lateral epicondyle, the
adductor tubercle, the fibular head and the centre of the knee to the joint line
were determined. RESULTS: The average distance to the joint line from the medial
epicondyle, the lateral epicondyle, the adductor tubercle and the fibular head
was found to be 27.7 mm (SD 3.0), 27.1 mm (SD 2.7), 44.6 mm (SD 4.3) and 15.1 mm
(SD 3.7), respectively. The distance from the adductor tubercle (R = 0.82) and
the centre of the knee (R = 0.86) to the joint line showed a strong and linear
correlation with the femoral width. The medial epicondyle, the lateral epicondyle
and the fibular head showed less strong correlations. There was no significant
correlation with the limb alignment. The adductor ratio was defined as the
distance from adductor tubercle to the joint line divided by the femoral width
and was found to be 0.52 (SD 0.027) with only small inter-individual variation.
The adductor ratio was the most accurate ratio and reconstructed the joint line
within 4 mm of its original level in 92% of the cases. CONCLUSION: The adductor
ratio is a reliable and accurate tool for joint line reconstruction in revision
TKA. It was found to be more accurate then the use of absolute distances and the
epicondylar ratios. This study supports the use of the adductor tubercle for
joint line reconstruction in revision TKA. LEVEL OF EVIDENCE: II.
PMID- 25135280
TI - Early surrender to knee arthroplasty.... Not so fast.... Let the knee tissue
preservation and function sustainability dialogue begin!
PMID- 25135278
TI - Infiltrating T cells promote prostate cancer metastasis via modulation of FGF11
>miRNA-541->androgen receptor (AR)->MMP9 signaling.
AB - Early clinical studies suggested infiltrating T cells might be associated with
poor outcomes in prostate cancer (PCa) patients. The detailed mechanisms how T
cells contribute to PCa progression, however, remained unclear. Here, we found
PCa cells have a better capacity to recruit more CD4(+) T cells than the
surrounding normal prostate cells via secreting more chemokines-CXCL9. The
consequences of more recruited CD4(+) T cells to PCa might then lead to enhance
PCa cell invasion. Mechanism dissection revealed that infiltrating CD4(+) T cells
might function through the modulation of FGF11->miRNA-541 signals to suppress PCa
androgen receptor (AR) signals. The suppressed AR signals might then alter the
MMP9 signals to promote the PCa cell invasion. Importantly, suppressed AR signals
via AR-siRNA or anti-androgen Enzalutamide in PCa cells also enhanced the
recruitment of T cells and the consequences of this positive feed back regulation
could then enhance the PCa cell invasion. Targeting these newly identified
signals via FGF11-siRNA, miRNA-541 inhibitor or MMP9 inhibitor all led to
partially reverse the enhanced PCa cell invasion. Results from in vivo mouse
models also confirmed the in vitro cell lines in co-culture studies. Together,
these results concluded that infiltrating CD4(+) T cells could promote PCa
metastasis via modulation of FGF11->miRNA-541->AR->MMP9 signaling. Targeting
these newly identified signals may provide us a new potential therapeutic
approach to better battle PCa metastasis.
PMID- 25135282
TI - Upper-extremity spinal reflex inhibition is reproducible and strongly related to
grip force poststroke.
AB - PURPOSE: Impaired reflex regulation is assumed to contribute to upper-extremity
motor impairment poststroke; however, the relationship between reflex inhibition
and motor function remains unclear. To address this question, it is first
necessary to determine the reproducibility of reflex responses. The objective of
this study was to establish the test-retest reliability of flexor carpi radialis
H-reflex inhibition in healthy control and stroke participants and investigate
the correlation between H-reflex inhibition and grip strength. MATERIALS AND
METHODS: Eighteen persons poststroke (mean +/- SD: age 63 +/- 13 years; 6 +/- 5
years poststroke; 13 males) and 16 healthy controls (age: 62 +/- 12 years)
participated. Reflex inhibition was tested on 2 separate days by conditioning the
H-reflex with radial nerve stimulation at two different interstimulus intervals:
13 ms (presynaptic Ia inhibition-PSI) and 0 ms (disynaptic inhibition). Pearson's
and intraclass correlation coefficients [two-way mixed model-ICC (1, 2)], and
standard error of measurement (SEM) were calculated. RESULTS: Relative
reliability (ICCs) ranged from good to excellent (0.61-0.78). SEM was low (range
10-19%, stroke; 15-20%, healthy controls). Paretic grip strength and paretic limb
PSI revealed a positive correlation (r = 0.70; p < 0.0125). Disynaptic inhibition
and paretic grip strength were not correlated. CONCLUSIONS: To our knowledge,
this is the first study to demonstrate reproducibility of reflex inhibition in
individuals poststroke. Furthermore, we quantify smallest real differences, which
provide an estimate of the magnitude of effect required to determine a meaningful
change, exceeding measurement error. The correlation between PSI and grip
strength suggests the potential contribution of PSI to grip force production and
upper-extremity motor function.
PMID- 25135283
TI - A familial form of benign paroxysmal positional vertigo maps to chromosome 15.
AB - AIM: Benign positional paroxysmal vertigo (BPPV) is characterized by short-lived
episodes of vertigo in association with rapid changes in head position, most
commonly extension and rotation of the neck while supine. It has been clinically
observed that there is a subgroup of patients in whom the BPPV disease is
inherited in an autosomal dominant fashion. However, little is known about the
familial/genetic factors that may contribute to a predisposition to develop the
disease. MATERIALS AND METHODS: We ascertained and performed a genome-wide scan
on a three-generation family in which multiple family members developed BPPV. We
performed whole genome mapping with 400 microsatellite repeat markers and
analyzed this trait using both autosomal dominant and recessive models of
inheritance. RESULTS: Two point linkage analysis showed LOD scores of one or
greater than one on chromosomes 7, 15, 16 and 20. Independent of the model of
inheritance, the highest two-point LOD scores localized to same marker on
chromosome 15. Multipoint linkage analysis showed the highest LOD score of 2.84
to markers on chromosome 15 with the autosomal dominant model. Haplotype
reconstruction indicates that the BPPV gene in this family maps to a critical
chromosomal 15 interval between markers GATA151F03N and GATA85D02. CONCLUSIONS:
Discovery of a BPPV gene (or genes) will facilitate a better understanding of not
only BPPV, but also the vestibular system. In addition, with improved
understanding of the pathophysiology the potential development of alternative
therapies for BPPV may be possible.
PMID- 25135281
TI - The tumor suppressor prostate apoptosis response-4 (Par-4) is regulated by mutant
IDH1 and kills glioma stem cells.
AB - Prostate apoptosis response-4 (Par-4) is an endogenous tumor suppressor that
selectively induces apoptosis in a variety of cancers. Although it has been the
subject of intensive research in other cancers, less is known about its
significance in gliomas, including whether it is regulated by key driver
mutations, has therapeutic potential against glioma stem cells (GSCs), and/or is
a prognostic marker. We found that patient-derived gliomas with mutant isocitrate
dehydrogenase 1 have markedly lower Par-4 expression (P < 0.0001), which was
validated by The Cancer Genome Atlas dataset (P = 2.0 E-13). The metabolic
product of mutant IDH1, D-2-hydroxyglutarate (2-HG), can suppress Par-4
transcription in vitro via inhibition of promoter activity as well as enhanced
mRNA degradation, but interestingly not by direct DNA promoter hypermethylation.
The Selective for Apoptosis induction in Cancer cells (SAC) domain within Par-4
is highly active against glioma cells, including orthotopic xenografts of patient
derived primary GSCs (P < 0.0001). Among high-grade gliomas that are IDH1 wild
type, those that express more Par-4 have significantly longer median survival
(18.4 vs. 8.0 months, P = 0.002), a finding confirmed in two external GBM
cohorts. Together, these data suggest that Par-4 is a significant component of
the mutant IDH1 phenotype, that the activity of 2-HG is complex and can extend
beyond direct DNA hypermethylation, and that Par-4 is a promising therapeutic
strategy against GSCs. Furthermore, not every effect of mutant IDH1 necessarily
contributes to the overall favorable prognosis seen in such tumors; inhibition of
Par-4 may be one such effect.
PMID- 25135284
TI - Occurrence of Hashimoto's thyroiditis among the patients with Sydenham's chorea.
AB - AIM: The purpose of this study was to examine the possible association of
Hashimoto's thyroiditis (HT) with Sydenham's chorea (SC). MATERIALS AND METHODS:
A total of 25 SC patients and 25 patients with the diagnosis of HT were included
in the study. Neurological, cardiac, radiological abnormalities, clinical
findings, and biochemical analysis were evaluated. RESULTS: Heart murmur as a
result of mitral valve deformation was present in all SC group patients. No
neurologic and cardiac abnormalities were noted in HT group. Serum thyroid
stimulating hormone (TSH), anti-thyroid peroxidase, and anti-thyroglobulin levels
were found to be high in 4 patients of the SC group and called as SC with HT
group. Significant elevation of serum TSH levels in SC with HT group (31.75 +/-
3.71 MUU/ml) was observed when compared to HT group (12.60 +/- 4.24 MUU/ml, p <
0.05). CONCLUSION: These results showed that HT can be occurred among the
patients with SC with cardiac involvement.
PMID- 25135285
TI - Glycemic control: a combination of lifestyle management and the use of drugs.
AB - Some 30% of contemporary cardiology patients have coexisting known diabetes, and
another 40% have either undiagnosed diabetes or prediabetes. There is still no
final conclusive evidence of cardiovascular benefit by good glycemic control in
type 2 diabetes, although studies like the United Kingdom Prospective Diabetes
Study (UKPDS) and the Prospective Pioglitazone Clinical Trial in Macrovascular
Events, and meta-analyses based on these and other randomized controlled trials
of blood glucose-lowering therapies have been encouraging. On the other hand,
microvascular disease is clearly reduced by good glycemic control. Structured
education has remained a mandatory prerequisite of any successful treatment. Not
only is appropriate weight management by diet and exercise able to revert new
onset diabetes to normal, but it is also the foundation of any successful
pharmacotherapy of diabetes. Aiming at normal fasting plasma glucose
concentrations of 5.3 mmol/L or 95 mg/dL appears to be safe since publication of
the long-term outcome results of the Outcome Reduction with an Initial Glargine
INtervention trial. Individualized target glycosylated hemoglobin levels as near
to normal as safely possible (i.e., <7% and avoiding hypoglycaemia) are the goal
for glycemic control. Hypoglycemia seems to emerge as a real concern in
cardiology patients. Based on the findings of UKPDS, including the "legacy"
study, metformin is the most widely recommended first-line drug therapy in type 2
diabetes, also in terms of preventing cardiovascular complications. An alternate
first-line option in some parts of the world, especially Asian countries, is the
class of alpha-glucosidase inhibitors. In most patients, combination therapies
with two or three classes of drugs are warranted. Early combination are the
golden strategy as type 2 diabetes is a multi-causal disease; the various classes
of drugs have distinct and synergistic modes of action, and the blood glucose
lowering efficacy of these drugs is more or less fully maintained in combination.
The recent joint American Diabetes Association/European Association for the Study
of Diabetes position statement mentions five options as step two of the treatment
algorithm for combination with metformin: sulfonylureas, pioglitazone, dipeptidyl
peptidase-4 inhibitors, glucagon-like peptide-1 agonists, and basal insulin.
PMID- 25135286
TI - The resoluteTM integrity zotarolimus-eluting stent in coronary artery disease: a
review.
AB - The introduction of first-generation drug-eluting stents (DES) was a major
advance in the percutaneous treatment of coronary artery disease, with DES
significantly reducing the incidence of restenosis and major adverse coronary
events compared with bare metal stents. Next-generation DES now utilizes lower
profiles, thinner struts, and other technological advances to help extend their
safety and efficacy. Importantly, studies of next-generation devices have now
gone beyond controlled clinical trials with selected populations to registries
and studies with all-comer populations, where more diverse and complex sets of
patients and lesions have been managed. Thus, a large body of evidence and
comparative data about the safety and efficacy of these devices has accumulated.
The ResoluteTM zotarolimus-eluting stent (R-ZES; Medtronic Inc., Santa Rosa, CA,
USA) is a next-generation DES that uses a novel biocompatible polymer on a cobalt
alloy stent platform to extend the duration of drug elution and improve the
stent's efficacy. The IntegrityTM platform (Medtronic, Inc., Santa Rosa, CA, USA)
used in the most recent iteration of the R-ZES stent further enhances the
flexibility and deliverability of the stent in complex lesions by incorporation
of a continuous sinusoidal design. In the following review, the clinical data is
critically examined for the R-ZES and discuss its performance using comparative
data currently available for next-generation DES. It is concluded that R-ZES use
in complex patients and lesions is associated with durable efficacy and safety
and represents another generational improvement in DES technology, which
undoubtedly will enhance patient outcomes postpercutaneous coronary
interventional.
PMID- 25135287
TI - Current and emerging antiarrhythmic drug therapy for ventricular tachycardia.
AB - Ventricular arrhythmias, including ventricular fibrillation (VF) and sustained
ventricular tachycardia (VT), are the principal causes of sudden cardiac death in
patients with structural heart disease. While coronary artery disease is the
predominant substrate associated with the development of VT, these arrhythmias
are known to occur in a variety of disorders, including dilated cardiomyopathy,
valvular and congenital heart disease, and cardiac ion channelopathies such as
the long QT syndrome. In a minority of patients, VT occurs in the absence of
structural heart disease. Despite the established mortality benefit of the
implantable cardioverter defibrillator (ICD) in patients at risk of lethal
arrhythmias, recurrent VT/VF events continue to be a source of morbidity and
impaired quality of life in such patients. Antiarrhythmic therapy is indicated in
select patients to treat symptomatic VT episodes, to reduce the incidence of ICD
shocks, and potentially to improve quality of life and reduce hospitalizations
related to cardiac arrhythmia. The primary adverse effects of antiarrhythmic
medications are related to both cardiac and extracardiac toxicity, including the
risk of proarrhythmia. Current drug therapy for ventricular arrhythmia has been
limited by suboptimal efficacy in many patients, resulting in recurrent VT/VF
events, and by drug toxicity or intolerance leading to discontinuation in a large
percentage of patients. Amiodarone and sotalol are the principal agents used in
the chronic treatment of VT. In addition, dronedarone and dofetilide, agents
approved for the treatment of atrial fibrillation, and ranolazine, an antianginal
agent, have been demonstrated to be protective against ventricular arrhythmia in
small clinical studies. Finally, advances in basic electrophysiology have
uncovered new molecular targets for the treatment of ventricular arrhythmia, and
pharmacologic agents directed at these targets may emerge as promising VT
treatments in the future. The roles of these current and emerging therapies for
the treatment of VT in humans will be summarized in this review.
PMID- 25135288
TI - Oral antiplatelet therapy in acute coronary syndromes: recent developments.
AB - The purpose of this article is to summarize the current knowledge about treatment
with oral platelet inhibitors in patients with acute coronary syndrome (ACS).
Antiplatelet therapy has been shown to improve the prognosis of patients with ACS
with ST segment elevation myocardial infarction (STEMI) and non-ST segment
elevation ACS (NSTE-ACS). Aspirin should be given with a loading dose of 250-500
mg, followed by 75-100 mg/day. Dual antiplatelet therapy is recommended for all
patients with ACS for 12 months regardless of the initial revascularization
strategy. Clopidogrel should be administered at first medical contact in STEMI
with a loading dose of 600 mg. In patients with ACS and percutaneous coronary
intervention (PCI) 2 * 75 mg clopidogrel should be given daily over 7 days, while
in all other patients 75 mg per day appears to be sufficient. The two newer
adenosine diphosphate-receptor antagonists prasugrel and ticagrelor lead to a
more rapid and effective inhibition of platelet aggregation compared with
clopidogrel, which was associated with an improved clinical outcome in two large
randomized studies. Prasugrel is indicated in patients with ACS undergoing PCI
and was most effective in diabetics and in patients with STEMI. In the recent
TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage
Acute Coronary Syndromes trial in medically treated patients with NSTE-ACS,
prasugrel did not significantly reduce ischemic events compared with clopidogrel.
Ticagrelor has been studied in the whole spectrum of ACS patients and reduced
cardiovascular and total mortality in comparison with clopidogrel. The greatest
benefit has been observed in patients with planned conservative treatment and in
patients with impaired renal function. Expanding antiplatelet therapy from dual
to triple therapy including a platelet thrombin receptor antagonist in the
thrombin receptor antagonist for clinical event reduction in acute coronary
syndrome trial was not associated with a significant reduction in the primary
combined endpoint but an increase in bleeding complications. However, in the
Thrombin Receptor Antagonist in Secondary Prevention of atherothrombotic ischemic
events study in patients with prior myocardial infarction, vorapaxar on top of
standard antiplatelet therapy was effective.
PMID- 25135289
TI - Thrombin receptor antagonism in antiplatelet therapy.
AB - Activated platelets play a crucial role in the pathogenesis of atherothrombotic
disease and its complications. Even under treatment of antiplatelet drugs, such
as acetylsalicylic acid and P2Y12 antagonists, morbidity and mortality rates of
thromboembolic complications remain high. Hence, the therapeutic inhibition of
protease-activated receptor (PAR)-1, which is activated by thrombin, is a novel
promising approach in antiplatelet therapy. Recent data suggest that PAR-1 is
mainly involved in pathological thrombus formation, but not in physiological
hemostasis. Therefore, PAR-1 inhibition offers the possibility to reduce
atherothrombotic events without increasing bleeding risk. So far, two emerging
PAR-1 antagonists have been tested in clinical trials: vorapaxar (SCH530349;
Merck & Co., Whitehouse Station, NJ, USA) and atopaxar (E5555; Eisai, Tokyo,
Japan). Although in TRA-CER vorapaxar showed an unfavorable profile for patients
with acute coronary syndrome in addition to standard therapy, it revealed
promising results for patients with prior myocardial infarction in TRA 2P-TIMI50.
Depending on the status of clinical approval, vorapaxar might be an option for
patients with peripheral arterial disease to reduce limb ischemia. The second PAR
I antagonist, atopaxar, tended towards reducing major cardiovascular adverse
events in acute coronary syndrome patients in a phase II trial. However, although
statistically not significant, bleeding events were numerically increased in
atopaxar-treated patients compared with placebo. Furthermore, liver enzymes were
elevated and the relative corrected QT interval was prolonged in atopaxar-treated
patients. Currently, the development of atopaxar by Eisai is discontinued. The
future of this novel class of antithrombotic drugs will depend on the
identification of patient groups in which the risk-benefit ratio is favorable.
PMID- 25135290
TI - Optimal choice of coronary revascularization and stent type in diabetic patients
with coronary artery disease.
AB - Patients with diabetes mellitus (DM) are prone to a diffuse and accelerated form
of coronary artery disease (CAD), which in turn is a major cause of cardiac
related morbidity and mortality. Compared with patients without diabetes,
patients with diabetes undergoing coronary revascularization are at higher risk
of procedural, short-, and long-term cardiovascular events and mortality.
Although coronary artery bypass grafting (CABG) has been regarded as the primary
revascularization strategy in diabetic patients with complex CAD, percutaneous
coronary intervention (PCI) is an effective revascularization alternative, due to
remarkable advances in stent devices and adjunctive drug therapies. Outcomes
data, from subgroup analyses and small-sized clinical trials and large
registries, have suggested that PCI with current stent technology showed
comparable long-term risks of mortality and hard endpoints, but higher risk of
repeat revascularization for the diabetic population compared to CABG. However,
the recent landmark International Future REvascularization Evaluation in patients
with diabetes mellitus: optimal management of Multivessel disease (FREEDOM) trial
provides compelling evidence of the superiority of CABG over PCI in reducing the
rates of death, myocardial infarction, at the expense of stroke, in patients with
diabetes with advanced CAD. When opting for PCI in patients with diabetes,
currently used drug-eluting stents (DES) are more efficient in reducing the risk
of repeat revascularization without compromising safety outcomes, compared to
bare-metal stents. The selection of a specific type of DES in patients with
diabetes is controversial and therefore more data comparing second- and newer
generation DES for patients with diabetes are currently needed. Also, efforts to
make more advanced DES platforms suitable for patients with diabetes with
complicated angiographic features are still ongoing.
PMID- 25135291
TI - Balancing antiplatelet and anticoagulant therapies in patients with
cardiovascular disease.
AB - Anticoagulation is needed for stroke prevention in patients with atrial
fibrillation. Antiplatelet therapy is essential for the prevention of stent
thrombosis and the reduction of cardiovascular events in patients who undergo
coronary stenting and suffer acute coronary syndromes. When these conditions
overlap, the individual antithrombotic strategies are commonly combined, and the
efficacy benefit of triple oral antithrombotic therapy is assumed to outweigh the
bleeding risk based on the available data. Recent studies have investigated this
topic further, including the first randomized controlled trial to address this
issue. This new evidence challenges previous assumptions and may have
implications for future practice and investigation.
PMID- 25135292
TI - Fenestrated atrial septal defect percutaneously occluded by a single device:
procedural and financial considerations.
AB - A 45-year-old patient presented with a cerebrovascular attack and was
subsequently found to have a multi-fenestrated atrial septal defect. Various
therapeutic options for percutaneous transcatheter closure with their respective
benefits and flaws are discussed, as well as procedural and financial
considerations. The decision making process leading to a successful result using
a single occlusive device is presented, alongside a review of the literature.
PMID- 25135293
TI - An extremely rare combination: pneumopericardium, pneumoperitoneum, and
subcutanous emphysema-a case report.
AB - Pneumopericardium, an accumulation of air in the pericardial cavity, occurs very
rarely as compared to pneumothorax and pneumomediastinum. Clinical presentation
is variable, patients are frequently asymptomatic, and mild cases usually resolve
spontaneously. However, it may lead to pericardial tamponade, which requires
rapid diagnosis and treatment that can be lifesaving. The traditional diagnostic,
simple method of diagnosis is via an upright chest X-ray. Typical findings can be
detected and a differential diagnosis can be made between pneumomediastinum and
pneumopericardium. Echocardiography and chest computed tomography scans can also
support the diagnosis. Only one case of pneumopericardium after surgical
pericardiotomy has been reported in the literature so far. In this case report,
iatrogenic pneumopericardium, which resolved spontaneously after surgical
pericardiotomy, was reported in a 19-year-old patient who had a rejected liver
transplantation, and had liver and kidney failure with pericardial tamponade. In
this case, pneumopericardium was accompanied by pneumoperitoneum and subcutaneous
emphysema; an extremely rare combination.
PMID- 25135295
TI - Anti-inflammatory effect of a novel food Cordyceps guangdongensis on experimental
rats with chronic bronchitis induced by tobacco smoking.
AB - Cordyceps guangdongensis T. H. Li, Q. Y. Lin & B. Song (Cordycipitaceae) is a
novel food approved by the Ministry of Public Health of China in 2013.
Preliminary studies revealed that this novel food has multiple pharmacological
activities such as anti-fatigue effect, antioxidant ability, prolonging life,
anti-avian influenza virus activity, and therapeutic effect on chronic renal
failure. However, the anti-inflammatory effect on chronic bronchitis and the
effective constituent are still unknown. The purpose of this study was to
investigate both the anti-inflammatory effect of the edible fungus on
experimental rats with chronic bronchitis induced by tobacco smoking, and the
pilot effective constituent. Test rats were intragastrically administered with 3
doses of hot-water extract from C. guangdongensis (0.325, 0.65 and 1.30 g kg(-1)
bw daily for low, middle and high dose, respectively) for 26 days. Biochemical
indices and histological examinations in rats with chronic bronchitis induced by
tobacco smoking were determined. The content and molecular weights of the
polysaccharide from the hot-water extract were detected by the phenol-sulfuric
acid method and gel permeation chromatography, respectively. Biochemical indices
in the low, middle and high-dose groups with the hot-water extract of C.
guangdongensis were only 53.4%, 46.0% and 40.4% of those in the model control
group (total leukocytes), respectively; 70.7%, 60.3% and 58.1% (macrophages);
33.0%, 26.8% and 16.1% (neutrophils); and 22.2%, 23.5% and 13.6% (lymphocytes) of
those in the model control group. The bronchial lesions and inflammatory cell
infiltration were significantly alleviated in all groups with hot-water extract
of C. guangdongensis. This study indicates that the hot-water extract from C.
guangdongensis has a significant anti-inflammatory effect on chronic bronchitis.
The content of the polysaccharide was 6.92%; the molecular weights of the 3
polysaccharide components were respectively 1.28 * 10(6), 2.36 * 10(4) and 5.21 *
10(3) Da.
PMID- 25135294
TI - Dabigatran excess: case report and review of the literature.
AB - INTRODUCTION: Novel oral anticoagulants are increasingly used for stroke
prophylaxis in patients with non-valvular atrial fibrillation. While these agents
offer a more predictable pharmacokinetic profile, the lack of readily available
laboratory tests to monitor the level of anticoagulation and absence of an
antidote or established therapies to reverse the anticoagulant effect make
management of cases of over-anticoagulation challenging. CASE REPORT: In this
case report an 87-year-old man with a history of atrial fibrillation presented
with dabigatran excess in the setting of life-threatening, acute renal and
hepatic failure. The authors review the use of dabigatran in elderly patients,
the available data on management of patients with excess anticoagulation, and the
potential options for reversal of the anticoagulation effect. CONCLUSION: Further
investigation into reliable means of monitoring and reversing the anticoagulant
effect of dabigatran is crucial to the management of such patients.
PMID- 25135296
TI - VLA-4 blockade promotes differential routes into human CNS involving PSGL-1
rolling of T cells and MCAM-adhesion of TH17 cells.
AB - The focus of this study is the characterization of human T cell blood-brain
barrier migration and corresponding molecular trafficking signatures. We examined
peripheral blood and cerebrospinal fluid immune cells from patients under long
term anti-very late antigen-4 (VLA-4)/natalizumab therapy (LTNT) and from CNS
specimens. LTNT patients' cerebrospinal fluid T cells exhibited healthy central
/effector-memory ratios, but lacked CD49d and showed enhanced myeloma cell
adhesion molecule (MCAM) expression. LTNT led to an increase of PSGL-1 expression
on peripheral T cells. Although vascular cell adhesion molecule-1 (VLA-4
receptor) was expressed at all CNS barriers, P-selectin (PSGL-1-receptor) was
mainly detected at the choroid plexus. Accordingly, in vitro experiments under
physiological flow conditions using primary human endothelial cells and LTNT
patients' T cells showed increased PSGL-1-mediated rolling and residual adhesion,
even under VLA-4 blockade. Adhesion of MCAM(+)/TH17 cells was not affected by VLA
4 blocking alone, but was abrogated when both VLA-4 and MCAM were inhibited.
Consistent with these data, MCAM(+) cells were detected in white matter lesions,
and in gray matter of multiple sclerosis patients. Our data indicate that
lymphocyte trafficking into the CNS under VLA-4 blockade can occur by using the
alternative adhesion molecules, PSGL-1 and MCAM, the latter representing an
exclusive pathway for TH17 cells to migrate over the blood-brain barrier.
PMID- 25135297
TI - Long-term survival of influenza virus infected club cells drives immunopathology.
AB - Respiratory infection of influenza A virus (IAV) is frequently characterized by
extensive immunopathology and proinflammatory signaling that can persist after
virus clearance. In this report, we identify cells that become infected, but
survive, acute influenza virus infection. We demonstrate that these cells, known
as club cells, elicit a robust transcriptional response to virus infection, show
increased interferon stimulation, and induce high levels of proinflammatory
cytokines after successful viral clearance. Specific depletion of these surviving
cells leads to a reduction in lung tissue damage associated with IAV infection.
We propose a model in which infected, surviving club cells establish a
proinflammatory environment aimed at controlling virus levels, but at the same
time contribute to lung pathology.
PMID- 25135298
TI - RUNX1-dependent RAG1 deposition instigates human TCR-delta locus rearrangement.
AB - V(D)J recombination of TCR loci is regulated by chromatin accessibility to RAG1/2
proteins, rendering RAG1/2 targeting a potentially important regulator of
lymphoid differentiation. We show that within the human TCR-alpha/delta locus,
Ddelta2-Ddelta3 rearrangements occur at a very immature thymic, CD34(+)/CD1a(
)/CD7(+dim) stage, before Ddelta2(Ddelta3)-Jdelta1 rearrangements. These strictly
ordered rearrangements are regulated by mechanisms acting beyond chromatin
accessibility. Importantly, direct Ddelta2-Jdelta1 rearrangements are prohibited
by a B12/23 restriction and ordered human TCR-delta gene assembly requires RUNX1
protein, which binds to the Ddelta2-23RSS, interacts with RAG1, and enhances RAG1
deposition at this site. This RUNX1-mediated V(D)J recombinase targeting imposes
the use of two Ddelta gene segments in human TCR-delta chains. Absence of this
RUNX1 binding site in the homologous mouse Ddelta1-23RSS provides a molecular
explanation for the lack of ordered TCR-delta gene assembly in mice and may
underlie differences in early lymphoid differentiation between these species.
PMID- 25135300
TI - Accumulation of adverse prognostic markers worsens prognosis in chronic
lymphocytic leukaemia.
PMID- 25135303
TI - Multi-component assembly and luminescence tuning of lanthanide hybrids based with
both zeolite L/A and SBA-15 through two organically grafted linkers.
AB - Both zeolite A/L and SBA-15 have been used to assemble novel photofunctional
multi-component lanthanide hybrid materials. Microporous zeolites A/L are first
functionalized by embedding lanthanide or zinc complexes (TTA =
thenoyltrifluoroacetone, TAA = trifluoroacetone, bipy = 2,2'-bipyridyl) into the
pores of zeolite A/L, and then the surface of functionalized zeolite A/L is
modified via covalent linkers from aromatic carboxylic acids (para-aminobenzoic
acid ABA and para-hydroxyl benzoic acid HBA) grafted by 3-(triethoxysilyl)-propyl
isocyanate (TEPIC). On the other hand, SBA-15 is modified by grafting covalent
linker phen-Si from the modification of 1,10-phenanthroline (phen) with TEPIC.
Further, another lanthanide ion is used to link both functionalized zeolites, A/L
and SBA-15, through the coordination with the two covalent linkers, ABS-Si (HBA
Si) and phen-Si, respectively. Subsequently, the obtained multicomponent
microporous-mesoporous hybrid materials are assembled and characterized using
XRD, FT-IR, UV-vis DRS, SEM, TEM and luminescent approaches (spectra, lifetimes
and quantum efficiencies). These hybrids with both microporous zeolite and SBA-15
mesoporous host possess favourable luminescent performance and some hybrid
systems present the high quantum efficiencies of 90%. Besides, the luminescent
color can be tuned by adjusting the composition of these hybrids, among which
four hybrids (S-phen-Eu-HBA-[ZA-Tb-bipy], S-phen-Eu-HBA-[ZA-Zn-bipy], S-phen-Eu
ABA-[ZA-Tb-TAA], S-phen-Eu-ABA-[ZL-Tb-bipy]) can be integrated to white light
emission.
PMID- 25135301
TI - Cannabis use by individuals with multiple sclerosis: effects on specific immune
parameters.
AB - Cannabinoids affect immune responses in ways that may be beneficial for
autoimmune diseases. We sought to determine whether chronic Cannabis use
differentially modulates a select number of immune parameters in healthy controls
and individuals with multiple sclerosis (MS cases). Subjects were enrolled and
consented to a single blood draw, matched for age and BMI. We measured monocyte
migration isolated from each subject, as well as plasma levels of
endocannabinoids and cytokines. Cases met definition of MS by international
diagnostic criteria. Monocyte cell migration measured in control subjects and
individuals with MS was similarly inhibited by a set ratio of phytocannabinoids.
The plasma levels of CCL2 and IL17 were reduced in non-naive cannabis users
irrespective of the cohorts. We detected a significant increase in the
endocannabinoid arachidonoylethanolamine (AEA) in serum from individuals with MS
compared to control subjects, and no significant difference in levels of other
endocannabinoids and signaling lipids irrespective of Cannabis use. Chronic
Cannabis use may affect the immune response to similar extent in individuals with
MS and control subjects through the ability of phytocannabinoids to reduce both
monocyte migration and cytokine levels in serum. From a panel of signaling
lipids, only the levels of AEA are increased in individuals with MS, irrespective
of Cannabis use or not. Our results suggest that both MS cases and controls
respond similarly to chronic Cannabis use with respect to the immune parameters
measured in this study.
PMID- 25135299
TI - Classical Flt3L-dependent dendritic cells control immunity to protein vaccine.
AB - DCs are critical for initiating immunity. The current paradigm in vaccine biology
is that DCs migrating from peripheral tissue and classical lymphoid-resident DCs
(cDCs) cooperate in the draining LNs to initiate priming and proliferation of T
cells. Here, we observe subcutaneous immunity is Fms-like tyrosine kinase 3
ligand (Flt3L) dependent. Flt3L is rapidly secreted after immunization; Flt3
deletion reduces T cell responses by 50%. Flt3L enhances global T cell and
humoral immunity as well as both the numbers and antigen capture capacity of
migratory DCs (migDCs) and LN-resident cDCs. Surprisingly, however, we find
immunity is controlled by cDCs and actively tempered in vivo by migDCs. Deletion
of Langerin(+) DC or blockade of DC migration improves immunity. Consistent with
an immune-regulatory role, transcriptomic analyses reveals different skin migDC
subsets in both mouse and human cluster together, and share immune-suppressing
gene expression and regulatory pathways. These data reveal that protective
immunity to protein vaccines is controlled by Flt3L-dependent, LN-resident cDCs.
PMID- 25135304
TI - Occurrence of hemocyanin in ostracod crustaceans.
AB - Hemocyanin is a copper-containing protein that transports O2 in the hemolymph of
many arthropod species. Within the crustaceans, hemocyanin appeared to be
restricted to Malacostraca but has recently been identified in Remipedia. Here,
we report the occurrence of hemocyanin in ostracods, indicating that this
respiratory protein is more widespread within crustaceans than previously
thought. By analyses of expressed sequence tags and by RT-PCR, we obtained four
full length and nine partial hemocyanin sequences from six of ten investigated
ostracod species. Hemocyanin was identified in Myodocopida (Actinoseta jonesi,
Cypridininae sp., Euphilomedes morini, Skogsbergia lerneri, Vargula tsujii) and
Platycopida (Cytherelloidea californica) but not in Podocopida. We found no
evidence for the presence of hemoglobin in any of these ostracod species. Like in
other arthropods, we identified multiple hemocyanin subunits (up to six) to occur
in a single ostracod species. Bayesian phylogenetic analyses showed that ostracod
hemocyanin subunit diversity evolved independently from that of other
crustaceans. Ostracod hemocyanin subunits were found paraphyletic, with
myodocopid and platycopid subunits forming distinct clades within those of the
crustaceans. This pattern suggests that ostracod hemocyanins originated from
distinct subunits in the pancrustacean stemline.
PMID- 25135302
TI - Immunization with P10 peptide increases specific immunity and protects
immunosuppressed BALB/c mice infected with virulent yeasts of Paracoccidioides
brasiliensis.
AB - Paracoccidioidomycosis is a systemic granulomatous disease caused by
Paracoccidioides spp. A peptide from the major diagnostic antigen gp43, named
P10, induces a T-CD4(+) helper-1 immune response in mice and protects against
intratracheal challenge with virulent P. brasiliensis. Previously, we evaluated
the efficacy of the P10 peptide alone or combined with antifungal drugs in mice
immunosuppressed and infected with virulent isolate of P. brasiliensis. In the
present work, our data suggest that P10 immunization leads to an effective
cellular immune response associated with an enhanced T cell proliferative
response. P10-stimulated splenocytes increased nitric oxide (NO) production and
induced high levels of IFN-gamma, IL-1beta and IL-12. Furthermore, significantly
increased concentrations of pro-inflammatory cytokines were also observed in lung
homogenates of immunized mice. P10 immunization was followed by minimal fibrosis
in response to infection. Combined with antifungal drugs, P10 immunization most
significantly improved survival of anergic infected mice. Administration of
either itraconazole or sulfamethoxazole/trimethoprim together with P10
immunization resulted in 100 % survival up to 200 days post-infection, whereas
untreated mice died within 80 days. Hence, our data show that P10 immunization
promotes a strong specific immune response even in immunocompromised hosts and
thus P10 treatment represents a powerful adjuvant therapy to chemotherapy.
PMID- 25135306
TI - Unusual phenomena in the reduction process of vanadium(v) on a graphite electrode
at high overpotentials.
AB - An abrupt increase in the Tafel slope and the charge transfer resistance (Rct) of
V(v) ions on a graphite electrode are both observed at a transition potential
(EK). The possible vanadium complexes such as V2O3(3+) might result in the change
of reduction mechanism and the unusual phenomena.
PMID- 25135305
TI - Melatonin and oestrogen treatments were able to improve neuroinflammation and
apoptotic processes in dentate gyrus of old ovariectomized female rats.
AB - The aim of this study was to determine the outcomes of oestrogen and melatonin
treatments following long-term ovarian hormone depletion on neuroinflammation and
apoptotic processes in dentate gyrus of hippocampi. Forty-six female Wistar rats
of 22 months of age were used. Twelve of them remained intact, and the other 34
were ovariectomized at 12 months of age. Ovariectomized animals were divided into
three groups and treated for 10 weeks with oestrogens, melatonin or saline. All
rats were killed by decapitation at 24 months of age, and dentate gyri were
collected. A group of 2 month-old intact female rats was used as young control.
The levels of pro-inflammatory cytokines and heat shock protein 70 (HSP 70) were
analysed by ELISA. The expressions of TNFalpha, IL1beta, GFAP, nNOS, iNOS, HO-1,
NFkappaB, Bax, Bad, AIF, Bcl2 and SIRT1 genes were detected by real-time (RT)
PCR. Western blots were used to measure the protein expression of NFkappaB p65,
NFkappaB p50/105, IkappaBalpha, IkappaBbeta, p38 MAPK, MAP-2 and synapsin I. We
have assessed the ability of 17beta-oestradiol and melatonin administration to
downregulate markers of neuroinflammation in the dentate gyrus of ovariectomized
female rats. Results indicated that 17beta-oestradiol and melatonin treatments
were able to significantly decrease expression of pro-inflammatory cytokines,
iNOS and HO-1 in the hippocampus when compared to non-treated animals. A similar
age- and long-term ovarian hormone depletion- related increase in GFAP was also
attenuated after both melatonin and oestradiol treatments. In a similar way to
oestradiol, melatonin decreased the activation of p38 MAPK and NFkappaB pathways.
The treatments enhanced the levels of synaptic molecules synapsin I and MAP-2 and
have been shown to modulate the pro-antiapoptotic ratio favouring the second and
to increase SIRT1 expression. These findings support the potential therapeutic
role of melatonin and oestradiol as protective anti-inflammatory agents for the
central nervous system during menopause.
PMID- 25135307
TI - An electrically switchable metal-organic framework.
AB - Crystalline metal organic framework (MOF) materials containing interconnected
porosity can be chemically modified to promote stimulus-driven (light, magnetic
or electric fields) structural transformations that can be used in a number of
devices. Innovative research strategies are now focused on understanding the role
of chemical bond manipulation to reversibly alter the free volume in such
structures of critical importance for electro-catalysis, molecular electronics,
energy storage technologies, sensor devices and smart membranes. In this letter,
we study the mechanism for which an electrically switchable MOF composed of
Cu(TCNQ) (TCNQ = 7,7,8,8-tetracyanoquinodimethane) transitions from a high
resistance state to a conducting state in a reversible fashion by an applied
potential. The actual mechanism for this reversible electrical switching is still
not understood even though a number of reports are available describing the
application of electric-field-induced switching of Cu(TCNQ) in device
fabrication.
PMID- 25135308
TI - The virtual toxicology service: wearable head-mounted devices for medical
toxicology.
PMID- 25135309
TI - Coming to a consensus on informed consent for case reports.
PMID- 25135311
TI - The S curve: a novel morphological finding in the internal carotid artery in
patients with fibromuscular dysplasia.
AB - Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease commonly
affecting the renal and internal carotid arteries (ICAs). A previously
unrecognized finding is a redundancy of the mid-distal ICA in FMD patients
causing an 'S'-shaped curve. Carotid artery duplex ultrasounds were reviewed in
116 FMD patients to determine S-curve prevalence. FMD patients with an S curve
were matched to four control patients divided equally into two groups: (1) age
and sex-matched and (2) age >=70 and sex-matched. S curves were present in 37
(32%) FMD patients. Of these, nine (24%) had angiographic evidence of FMD in
their ICA only, 13 (35%) had renal artery FMD only, and 15 (41%) had both ICA and
renal FMD. Two patients in the age and sex-matched group had S curves (odds ratio
16.86, 95% CI 3.92-72.48; p<0.0001) while 12 (16.2%) patients in the age >=70 and
sex-matched group had S curves (odds ratio 2.42, 95% CI 1.16-5.03; p=0.016). In
conclusion, the S curve is a novel morphological pattern of the mid-distal ICA.
While the S curve may not be specific, its presence in individuals <70 years old
should alert the clinician to the possibility that FMD is present.
PMID- 25135310
TI - Multi-centre analysis of incidental findings on low-resolution CT attenuation
correction images.
AB - OBJECTIVE: To review new incidental findings detected on low-resolution CT
attenuation correction (CTAC) images acquired during single-photon emission CT
(SPECT-CT) myocardial perfusion imaging (MPI) and to determine whether the CTAC
images had diagnostic value and warrant reporting. METHODS: A multicentre study
was performed in four UK nuclear medicine departments. CTAC images acquired as
part of MPI performed using SPECT were evaluated to identify incidental findings.
New findings considered to be clinically significant were evaluated further.
Positive predictive value (PPV) was determined at the time of definitive
diagnosis. RESULTS: Of 1819 patients studied, 497 (27.3%) had a positive CTAC
finding. 51 (2.8%) patients had findings that were clinically significant at the
time of the CTAC report and had not been previously diagnosed. Only four (0.2%)
of these were potentially detrimental to patient outcome. CONCLUSION: One centre
had a PPV of 0%, and the study suggests that these CTAC images should not be
reported. Two centres with more modern equipment had low PPVs of 0% and 6%,
respectively, and further research is suggested prior to drawing a conclusion.
The centre with best quality CT had a PPV of 67%, and the study suggests that
CTAC images from this equipment should be reported. ADVANCES IN KNOWLEDGE: This
study is unique compared with previous studies that have reported only the
potential to identify incidental findings on low-resolution CT images. This study
both identifies and evaluates new clinically significant incidental findings, and
it demonstrates that the benefit of reporting the CTAC images depends on the type
of equipment used.
PMID- 25135313
TI - Kinetics of nitrification in a fixed biofilm reactor using dewatered sludge-fly
ash composite ceramic particle as a supporting medium.
AB - A mathematical model system was derived to describe the kinetics of ammonium
nitrification in a fixed biofilm reactor using dewatered sludge-fly ash composite
ceramic particle as a supporting medium. The model incorporates diffusive mass
transport and Monod kinetics. The model was solved using a combination of the
orthogonal collocation method and Gear's method. A batch test was conducted to
observe the nitrification of ammonium-nitrogen ([Formula: see text]-N) and the
growth of nitrifying biomass. The compositions of nitrifying bacterial community
in the batch kinetic test were analyzed using PCR-DGGE method. The experimental
results show that the most staining intensity abundance of bands occurred on day
2.75 with the highest biomass concentration of 46.5 mg/L. Chemostat kinetic tests
were performed independently to evaluate the biokinetic parameters used in the
model prediction. In the column test, the removal efficiency of [Formula: see
text]-N was approximately 96 % while the concentration of suspended nitrifying
biomass was approximately 16 mg VSS/L and model-predicted biofilm thickness
reached up to 0.21 cm in the steady state. The profiles of denaturing gradient
gel electrophoresis (DGGE) of different microbial communities demonstrated that
indigenous nitrifying bacteria (Nitrospira and Nitrobacter) existed and were the
dominant species in the fixed biofilm process.
PMID- 25135312
TI - Arachnoid membrane: the first and probably the last piece of the roadmap.
AB - Most neurosurgical procedures could be performed noninvasively by working through
the natural corridors provided by the subarachnoid cisterns. In consequence, the
subarachnoid cisterns have been considered as the roadmaps for the
microneurosurgeons. The concept and the contents of the cisterns have been well
known and described, but the knowledge of the detailed anatomy of the arachnoid
membranes, which are the real septa of the cisterns and provide the practical and
important landmarks and planes for the dissections during the brain surgeries, is
still lacking. The present article reviews the previous reports of the
intracranial arachnoid membranes with a special emphasis on the microsurgical
anatomy and the clinical significance.
PMID- 25135314
TI - Microrespirometric characterization of activated sludge inhibition by copper and
zinc.
AB - We have developed a novel microrespirometric method to characterize the
inhibitory effects due to heavy metals on activated sludge treatment. This method
was based on pulse dynamic respirometry and involved the injection of several
pulses of substrate and inhibitors, of increasing concentration. Furthermore, we
evaluated the inhibitory effects of heavy metals (copper and zinc), substrate and
biomass concentrations, and pH on activated sludge activity. While higher biomass
concentrations counteracted the inhibitory effects of both copper and zinc,
higher substrate concentrations predominantly augmented the inhibitory effect of
copper but no significant change in inhibition by zinc was observed. pH had a
clear but relatively small effect on inhibition, partially explained by
thermodynamic speciation. We determined the key kinetic parameters; namely, the
half saturation constant (K S ) and the maximum oxygen uptake rate (OUR max ).
The results showed that higher heavy metal concentrations substantially decreased
K S and OUR max suggesting that the inhibition was uncompetitive.
PMID- 25135315
TI - Enhanced production of 2,3-butanediol by a genetically engineered Bacillus sp.
BRC1 using a hydrolysate of empty palm fruit bunches.
AB - A Bacillus species that produces 2,3-butanediol (2,3-BD), termed BRC1, was newly
isolated, and a 2,3-BD dehydrogenase (Bdh) from this species was identified and
characterized at the molecular and biochemical level. Sequence analysis revealed
that Bdh is homologous to D-2,3-BD dehydrogenases. An analysis of the enzymatic
properties of Bdh overexpressed in Escherichia coli confirmed the molecular
results, showing preferred activity toward D-2,3-BD. Optimum pH, temperature, and
kinetics determined for reductive and oxidative reactions support the
preferential production of 2,3-BD during cell growth. Overexpression of bdh under
the control of a xylose-inducible promoter resulted in increased enzyme activity
and enhanced 2,3-BD production in Bacillus sp. BRC1. Additionally, a hydrolysate
of cellulosic material, (empty palm fruit bunches), was successfully used for the
enhanced production of 2,3-BD in the recombinant Bacillus strain.
PMID- 25135316
TI - Assessment of metal artefact reduction around dental titanium implants in cone
beam CT.
AB - OBJECTIVES: The aim of this study was to investigate if the metal artefact
reduction (MAR) tool used in the software of the ORTHOPANTOMOGRAPH((r)) OP300
(Instrumentarium Dental, Tuusula, Finland) can improve the gray value levels in
post-operative implant scans. METHODS: 20 potential implant sites were selected
from 5 edentulous human dry mandibles. Each mandible was scanned by a CBCT
scanner, and images were produced under three different conditions: implant sites
drilled but no implants inserted, implants inserted without application of MAR
and implants inserted with application of MAR. Using Geomagic((r)) Studio 2012
(Geomagic, Morrisville, NC) and 3Diagnosys((r)) v. 5.3.1 (3Diemme((r)) SRL,
Cantu, Italy) software, three scans of each mandible were superimposed. The mean
gray value of identical regions of bone around the implants was derived for each
condition. The differences between gray value measurements at implant sites
derived from different conditions were assessed. RESULTS: A significant
difference was found between mean gray values from the scans with no implants
inserted and with implants inserted (with and without MAR) (p = 0.012). No
significant difference was revealed for gray values measured from scans with and
without MAR (p = 0.975). CONCLUSIONS: The MAR tool in the software of the
ORTHOPANTOMOGRAPH OP300 CBCT scanner does not significantly correct the voxel
gray values affected by the metal artefact in the vicinity of an implant in human
dry mandibles.
PMID- 25135318
TI - Preaggregated Ag nanoparticles in dry swellable gel films for off-the-shelf
surface-enhanced Raman spectroscopy.
AB - Large, thin (50 MUm) dry polymer sheets containing numerous surface-enhanced
Raman spectroscopy (SERS) active Ag nanoparticle aggregates have been prepared by
drying aqueous mixtures of hydroxyethylcelloulose (HEC) and preaggregated Ag
colloid in 10 * 10 cm molds. In these dry films, the particle aggregates are
protected from the environment during storage and are easy to handle; for
example, they can be cut to size with scissors. When in use, the highly swellable
HEC polymer allowed the films to rapidly absorb aqueous analyte solutions while
simultaneously releasing the Ag nanoparticle aggregates to interact with the
analyte and generate large SERS signals. Either the films could be immersed in
the analyte solution or 5 MUL droplets were applied to the surface; in the latter
method, the local swelling caused the active area to dome upward, but the swollen
film remained physically robust and could be handled as required. Importantly,
encapsulation and release did not significantly compromise the SERS performance
of the colloid; the signals given by the swollen films were similar to the very
high signals obtained from the parent citrate-reduced colloid and were an order
of magnitude larger than a commercially available nanoparticle substrate. These
"Poly-SERS" films retained 70% of their SERS activity after being stored for 1
year in air. The films were sufficiently homogeneous to give a standard deviation
of 3.2% in the absolute signal levels obtained from a test analyte, primarily due
to the films' ability to suppress "coffee ring" drying marks, which meant that
quantitative analysis without an internal standard was possible. The majority of
the work used aqueous thiophenol as the test analyte; however, preliminary
studies showed that the Poly-SERS films could also be used with nonaqueous
solvents and for a range of other analytes including theophylline, a therapeutic
drug, at a concentration as low as 1.0 * 10(-5) mol dm(-3) (1.8 mg/dm(3)), well
below the sensitivity required for theophylline monitoring where the target range
is 10-20 mg/dm(3).
PMID- 25135317
TI - Efficacy of CBCT for assessment of impacted mandibular third molars: a review -
based on a hierarchical model of evidence.
AB - A radiographic examination of mandibular third molars is meant to support the
surgeon in establishing a treatment plan. For years panoramic (PAN) imaging has
been the first choice method; however, where an overprojection is observed
between the third molar and the mandibular canal and when specific signs suggest
a close contact between the molar and the canal, CBCT may be indicated. The
present review provides an evaluation of the efficacy of CBCT for assessment of
mandibular third molars using a six-tiered hierarchical model by Fryback and
Thornbury in 1991. Levels 1-3 include studies on low evidence levels mainly
regarding the technical capabilities of a radiographic method and the diagnostic
accuracy of the related images. Levels 4-6 include studies on a higher level of
evidence and assess the diagnostic impact of a radiographic method on the
treatment of the patient in addition to the outcome for the patient and society
including cost calculations. Only very few high-evidence studies on the efficacy
of CBCT for radiographic examination of mandibular third molars exist and, in
conclusion, periapical or PAN examination is sufficient in most cases before
removal of mandibular third molars. However, CBCT may be suggested when one or
more signs for a close contact between the tooth and the canal are present in the
two-dimensional image-if it is believed that CBCT will change the treatment or
the treatment outcome for the patient. Further research on high-evidence levels
is needed.
PMID- 25135319
TI - Bioinspired microfluidic assay for in vitro modeling of leukocyte-endothelium
interactions.
AB - Current in vitro models of the leukocyte adhesion cascade cannot be used for real
time studies of the entire leukocyte adhesion cascade, including rolling,
adhesion, and migration in a single assay. In this study, we have developed and
validated a novel bioinspired microfluidic assay (bMFA) and used it to test the
hypothesis that blocking of specific steps in the adhesion/migration cascade
significantly affects other steps of the cascade. The bMFA consists of an
endothelialized microvascular network in communication with a tissue compartment
via a 3 MUm porous barrier. Human neutrophils in bMFA preferentially adhered to
activated human endothelial cells near bifurcations with rolling and adhesion
patterns in close agreement with in vivo observations. Treating endothelial cells
with monoclonal antibodies to E-selectin or ICAM-1 or treating neutrophils with
wortmannin reduced rolling, adhesion, and migration of neutrophils to 60%, 20%,
and 18% of their respective control values. Antibody blocking of specific steps
in the adhesion/migration cascade (e.g., mAb to E-selectin) significantly
downregulated other steps of the cascade (e.g., migration). This novel in vitro
assay provides a realistic human cell based model for basic science studies,
identification of new treatment targets, selection of pathways to target
validation, and rapid screening of candidate agents.
PMID- 25135321
TI - Health related quality of life is differently associated with leisure-time
physical activity intensities according to gender: a cross-sectional approach.
AB - BACKGROUND: Several studies have demonstrated a positive association between
physical activity (PA) and health-related quality of life (HRQL). However,
studies have suggested that this association depends both on the PA intensity and
the domain of HRQL evaluated. This study aimed to explore the association between
physical, mental and overall HRQL with recommended levels of PA. PA levels were
divided into moderate and vigorous intensity leisure-time PA and total leisure
time PA. METHODS: The study included 1001 adults, 582 women (46 +/- 17 years) and
419 men (43 +/- 16 years), residents in Rio Claro-SP, Brazil. All participants
completed the SF-36 questionnaire to assess HRQL and the long version of the
International Physical Activity Questionnaire (IPAQ) to assess level and
intensities of leisure-time PA. Total leisure-time PA at moderate intensity was
classified as: less than 9 min/week, 10-149 min/week, 150-299 min/week and 300
min/week or more. Total leisure-time PA at vigorous intensity was classified as:
less than 9 min/week, 10 to 74.9 min/week, 75-149 min/week and 150 min/week or
more. Multiple linear regression was performed in STATA version 12.0. RESULTS:
Among women, moderate intensity and total leisure-time PA were associated with
physical health. Among men, moderate and vigorous intensity and total leisure
time PA were associated with physical health and overall HRQL. Furthermore,
moderate intensity and total leisure-time PA were associated with mental health
in men. However, vigorous intensity PA was not associated with mental health for
this group. CONCLUSION: The different domains of HRQL were associated with
different levels and intensities of PA in leisure-time according to gender of
adults. These findings indicate the complexity and importance of evaluating the
HRQL stratified by gender and consider the different levels and intensities of
PA.
PMID- 25135320
TI - Development of phage immuno-loop-mediated isothermal amplification assays for
organophosphorus pesticides in agro-products.
AB - Two immuno-loop-mediated isothermal amplification assays (iLAMP) were developed
by using a phage-borne peptide that was isolated from a cyclic eight-peptide
phage library. One assay was used to screen eight organophosphorus (OP)
pesticides with limits of detection (LOD) between 2 and 128 ng mL(-1). The iLAMP
consisted of the competitive immuno-reaction coupled to the LAMP reaction for
detection. This method provides positive results in the visual color of violet,
while a negative response results in a sky blue color; therefore, the iLAMP
allows one to rapidly detect analytes in yes or no fashion. We validated the
iLAMP by detecting parathion-methyl, parathion, and fenitrothion in Chinese
cabbage, apple, and greengrocery, and the detection results were consistent with
the enzyme-linked immunosorbent assay (ELISA). In conclusion, the iLAMP is a
simple, rapid, sensitive, and economical method for detecting OP pesticide
residues in agro-products with no instrumental requirement.
PMID- 25135322
TI - A high-throughput sequencing ecotoxicology study of freshwater bacterial
communities and their responses to tebuconazole.
AB - The pollution of lakes and rivers by pesticides is a growing problem worldwide.
However, the impacts of these substances on microbial communities are still
poorly understood, partly because next-generation sequencing (NGS) has rarely
been used in an ecotoxicology context to study bacterial communities despite its
interest for accessing rare taxa. Microcosm experiments were carried out to
evaluate the effects of tebuconazole (TBZ) on the structure and composition of
bacterial communities from two types of freshwater ecosystem (lakes and rivers)
with differing histories of pollutant contamination (pristine vs. previously
exposed sites). Pyrosequencing revealed that bacterial diversity was higher in
the river than in the lakes and in previously exposed sites than in pristine
sites. Lakes and river stations shared very few OTUs, and differences at the
phylum level were identified between these ecosystems (i.e. the relative
importance of Actinobacteria and Gammaproteobacteria). Despite differences
between these ecosystems and their contamination history, no significant effect
of TBZ on bacterial community structure or composition was observed. Compared to
functional parameters that displayed variable responses, we demonstrated that a
combination of classical methods and NGS is necessary to investigate the
ecotoxicological responses of microbial communities to pollutants.
PMID- 25135324
TI - Smaller pupil size and better proofreading performance with positive than with
negative polarity displays.
AB - The 'positive polarity advantage' describes the fact that reading performance is
better for dark text on light background (positive polarity) than for light text
on dark background (negative polarity). We investigated the underlying mechanism
by assessing pupil size and proofreading performance when reading positive and
negative polarity texts. In particular, we tested the display luminance
hypothesis which postulates that the typically greater brightness of positive
compared to negative polarity displays leads to smaller pupil sizes and, hence, a
sharper retinal image and better perception of detail. Indeed, pupil sizes were
smaller and proofreading performance was better with positive than with negative
polarity displays. The results are compatible with the hypothesis that the
positive polarity advantage is an effect of display luminance. Limitations of the
study are being discussed.
PMID- 25135323
TI - Serum lipid concentrations in patients with cholesterol and pigment gallstones.
AB - BACKGROUND: Gallstones (GS) are formed as a result of impaired metabolic
regulation of the human body. Abnormal lipid metabolism is partly responsible for
the pathogenesis of GS mainly rich in cholesterol. Thus abnormalities of serum
lipids would reflect the possibilities of the formation of cholesterol GS. This
study aims to identify the significance of serum lipids on the development of GS
disease. METHODS: Serum lipid profiles were estimated in 73 patients with
symptomatic GS, admitted to the Teaching Hospital, Peradeniya, Sri Lanka for GS
removal surgeries from May 2011 to December 2012. Patients with normal serum
bilirubin level and not being on lipid lowering drugs were recruited for the
study. Serum lipid profile of each patient was analyzed by enzymatic kit assays
and the chemical composition of GS was analyzed by Fourier Transform Infrared
spectroscopy. RESULTS: Of the 73 patients, 37 (51%) had cholesterol GS while 36
(49%) had pigment GS. Serum lipid parameters of a majority of patients were
within the normal range. Body mass index values of the patients with two types of
GS were not significantly different (Two sample t test, p = 0.335). Out of the
lipid parameters tested, only serum triglyceride concentration was significantly
high in patients with cholesterol GS than that of pigment GS (Two sample t test,
p = 0.038). None of the lipid parameters were significantly different between
males and females (Two sample t test, p > 0.05). Compared to the patients with
pigment GS who were aged below 50 years, mean total cholesterol and triglyceride
concentrations were higher in the same age category patients with cholesterol GS.
CONCLUSION: Abnormal serum lipid profiles doesn't seem to be an essential feature
in patients with cholesterol GS. However when the two groups of patients with
cholesterol and pigment GS with no significant difference of body mass indexes
were compared, patients with cholesterol GS are more likely to have serum lipid
parameters towards the undesirable cutoff levels of their respective normal
ranges. However an effect of serum lipid concentrations on high incidence of GS
among females has not been identified.
PMID- 25135325
TI - A novel wheat bZIP transcription factor, TabZIP60, confers multiple abiotic
stress tolerances in transgenic Arabidopsis.
AB - The basic region/leucine zipper (bZIP) transcription factors (TFs) play vital
roles in the response to abiotic stress. However, little is known about the
function of bZIP genes in wheat abiotic stress. In this study, we report the
isolation and functional characterization of the TabZIP60 gene. Three homologous
genome sequences of TabZIP60 were isolated from hexaploid wheat and mapped to the
wheat homoeologous group 6. A subcellular localization analysis indicated that
TabZIP60 is a nuclear-localized protein that activates transcription.
Furthermore, TabZIP60 gene transcripts were strongly induced by polyethylene
glycol, salt, cold and exogenous abscisic acid (ABA) treatments. Further analysis
showed that the overexpression of TabZIP60 in Arabidopsis resulted in
significantly improved tolerances to drought, salt, freezing stresses and
increased plant sensitivity to ABA in seedling growth. Meanwhile, the TabZIP60
was capable of binding ABA-responsive cis-elements that are present in promoters
of many known ABA-responsive genes. A subsequent analysis showed that the
overexpression of TabZIP60 led to enhanced expression levels of some stress
responsive genes and changes in several physiological parameters. Taken together,
these results suggest that TabZIP60 enhances multiple abiotic stresses through
the ABA signaling pathway and that modifications of its expression may improve
multiple stress tolerances in crop plants.
PMID- 25135326
TI - The medium term prognostic value of dobutamine stress echocardiogram in patients
with high risk scores of coronary artery disease according to NICE Clinical
Guideline 95.
PMID- 25135327
TI - Melioidosis: a rare cause of constrictive pericarditis.
PMID- 25135328
TI - Rosuvastatin treatment improves arterial stiffness with lowering blood pressure
in healthy hypercholesterolemic patients.
PMID- 25135329
TI - Transcatheter Amplatzer Duct Occluder II closure of perimembranous ventricular
septal defect with right lung agenesis.
PMID- 25135330
TI - The role of angioplasty in patients with acute coronary syndrome and previous
coronary artery bypass grafting.
AB - INTRODUCTION: Angioplasty has changed the management of acute coronary syndrome
(ACS). However, in patients with previous coronary artery bypass grafting (CABG),
the role of angioplasty in the management of ACS is widely debated. Lack of clear
guidelines leads to subjective and often stereotypical assessments based on
clinician preferences. We sought to investigate if angioplasty affected all cause
mortality in ACS patients with previous CABG. METHODS: Completely anonymous
information on patients with ACS with a background of previous CABG, co
morbidities and procedures attending three multi-ethnic general hospitals in the
North West of England, United Kingdom in the period 2000-2012 was traced using
the ACALM (Algorithm for Comorbidities, Associations, Length of stay and
Mortality) study protocol using ICD-10 and OPCS-4 coding systems. Predictors of
mortality and survival analyses were performed using SPSS version 20.0. RESULTS:
Out of 12,227 patients with ACS, there were 1172 (19.0%) cases of ACS in patients
with previous coronary artery bypass grafting. Of these 83 (7.1%) patients
underwent angioplasty. Multi-nominal logistic regression, accounting for
differences in age and co-morbidities, revealed that having angioplasty conferred
a 7.96 times improvement in mortality (2.36-26.83 95% CI) compared to not having
angioplasty in this patient group. CONCLUSIONS: We have shown that angioplasty
confers significantly improved all cause mortality in the management of ACS in
patients with previous CABG. The findings of this study highlight the need for
clinicians to conscientiously think about the individual benefits and risks of
angioplasty for every patient rather than confining to age related stereotypes.
PMID- 25135331
TI - Astragali Radix protects myocardium from ischemia injury by modulating energy
metabolism.
PMID- 25135332
TI - Wolff-Parkinson-White syndrome influenced by myocardial infarction?
PMID- 25135333
TI - Exercise ventilatory power in heart failure patients: functional phenotypes
definition by combining cardiopulmonary exercise testing with stress
echocardiography.
PMID- 25135334
TI - No clear evidence of a clinical benefit of a sequential therapy regimen with
abiraterone acetate and enzalutamide.
AB - Prostate cancer is the second leading cause of cancer-related deaths in men in
most western countries. New agents for metastatic castration-resistant prostate
cancer (CRPC) developed in the past 3 years include abiraterone acetate (AA) and
enzalutamide (ENZ), which inhibit signaling by and synthesis of androgens,
respectively. Because they share the same target, potential clinical cross
resistance between AA and E is possible. In this review, we discuss the results
of clinical studies in which CRPC patients were treated with AA and E either
separately or in sequence after first-line treatment with docetaxel. Our review
suggests that sequential administration of AA and E in either order has limited
activity after docetaxel therapy. Prospective studies that further examine
sequential treatments with AA and E are warranted.
PMID- 25135335
TI - A.S.P.E.N. data brief 2014: use of enteral and parenteral nutrition in
hospitalized patients with a diagnosis of malnutrition: United States, 2010.
PMID- 25135337
TI - Hospital-based study of dental pathology and faecal particle size distribution in
horses with large colon impaction.
AB - The aim of the study was to determine if horses with large colon impaction were
more severely affected by oral pathology than control cases and to relate faecal
particle size distribution to dental pathology in both study groups. A
prospective study included 39 horses with large colon impaction and 72 control
horses from a hospital-based population. An oral pathology score (OPscore) and
periodontal disease index (PDI) were assigned to all horses and faecal samples
were collected for estimating faecal particle size and analysis of particle size
distribution. Horses with large colon impactions were not more severely affected
by oral pathology than control horses for both OPscore (P = 0.2) and PDI (P =
0.3). Faecal particle size estimates were significantly higher in control animals
(P <0.001). No significant association was found between faecal particle size
estimates and OPscores in horses with large colon impaction or control horses. In
horses with large colon impaction, faecal particle size estimates increased with
increasing PDI (P = 0.05). No associations were found between dental pathology
and faecal particle size estimates. Horses developing large colon impaction did
not have worse dentition than control horses.
PMID- 25135338
TI - The pharmacokinetics and in vitro/ex vivo cyclooxygenase selectivity of parecoxib
and its active metabolite valdecoxib in cats.
AB - Parecoxib (PX) is an injectable prodrug of valdecoxib (VX, which is a selective
cyclo-oxyganase-2 (COX-2)) inhibitor licensed for humans. The aim of the present
study was to evaluate pharmacokinetics and in vitro/ex vivo cyclooxygenase
selectivity of PX and VX in cats. In a whole blood in vitro study, PX did not
affect either COX enzymes whereas VX revealed a COX-2 selective inhibitory effect
in feline whole blood. The IC50 values of VX for COX-2 and COX-1 were 0.45 and
38.6 uM, respectively. Six male cats were treated with 2.5 mg/kg of PX by
intramuscular injection. PX was rapidly converted to VX with a relatively short
half-life of 0.4 h. VX achieved peak plasma concentration (2.79 +/- 1.59 ug/mL)
at 7 h following PX injection. The mean residence times for PX and VX were 0.43
+/- 0.15 and 5.94 +/- 0.88 h, respectively. In the ex vivo study, PX showed a COX
2 inhibition rate of about 70% in samples taken at 1, 2, 4 and 10 h after
injection, with a significant difference compared to the control. In contrast,
COX-1 was slightly inhibited, ranging from 0.7% to 9.7% of the control inhibition
rate without any significant difference for 24 h after PX administration. The
preliminary findings of the present research appear promising and encourage
further studies to investigate whether PX can be successfully used in feline
medicine.
PMID- 25135340
TI - Experimental infection of highly pathogenic avian influenza virus H5N1 in black
headed gulls (Chroicocephalus ridibundus).
AB - Historically, highly pathogenic avian influenza viruses (HPAIV) rarely resulted
in infection or clinical disease in wild birds. However, since 2002, disease and
mortality from natural HPAIV H5N1 infection have been observed in wild birds
including gulls. We performed an experimental HPAIV H5N1 infection of black
headed gulls (Chroicocephalus ridibundus) to determine their susceptibility to
infection and disease from this virus, pattern of viral shedding, clinical signs,
pathological changes and viral tissue distribution. We inoculated sixteen black
headed gulls with 1 * 10(4) median tissue culture infectious dose HPAIV H5N1
(A/turkey/Turkey/1/2005) intratracheally and intraesophageally. Birds were
monitored daily until 12 days post inoculation (dpi). Oropharyngeal and cloacal
swabs were collected daily to detect viral shedding. Necropsies from birds were
performed at 2, 4, 5, 6, 7, and 12 dpi. Sampling from selected tissues was done
for histopathology, immunohistochemical detection of viral antigen, PCR, and
viral isolation. Our study shows that all inoculated birds were productively
infected, developed systemic disease, and had a high morbidity and mortality
rate. Virus was detected mainly in the respiratory tract on the first days after
inoculation, and then concentrated more in pancreas and central nervous system
from 4 dpi onwards. Birds shed infectious virus until 7 dpi from the pharynx and
6 dpi from the cloaca. We conclude that black-headed gulls are highly susceptible
to disease with a high mortality rate and are thus more likely to act as sentinel
species for the presence of the virus than as long-distance carriers of the virus
to new geographical areas.
PMID- 25135339
TI - Detection of antibodies against porcine epidemic diarrhea virus in serum and
colostrum by indirect ELISA.
AB - An indirect porcine epidemic diarrhea virus (PEDV) anti-immunoglobulin (Ig) G
ELISA based on the S1 portion of the spike protein was validated and compared
with an indirect immunofluorescence assay. In serum samples from experimentally
infected pigs (n = 35), anti-IgG PEDV antibodies were detected as early as 7 days
post-infection. In field serum samples (n = 239), the diagnostic sensitivity of
the S1 ELISA was 100% and the diagnostic specificity was 94%. The S1 ELISA showed
no cross-reactivity with antibodies against other porcine coronaviruses.
Colostrum samples (n = 133) were also tested for anti-PEDV IgG and IgA. The
diagnostic sensitivity was 92% for IgG and 100% for IgA, and the diagnostic
specificity was 90% for IgG and 99.4% for IgA. These data suggest that the S1
ELISA is a sensitive and specific test that could also be used to evaluate PEDV
colostral immunity.
PMID- 25135336
TI - Molecular determinants of magnesium-dependent synaptic plasticity at electrical
synapses formed by connexin36.
AB - Neuronal gap junction (GJ) channels composed of connexin36 (Cx36) play an
important role in neuronal synchronization and network dynamics. Here we show
that Cx36-containing electrical synapses between inhibitory neurons of the
thalamic reticular nucleus are bidirectionally modulated by changes in
intracellular free magnesium concentration ([Mg(2+)]i). Chimeragenesis
demonstrates that the first extracellular loop of Cx36 contains a Mg(2+)
sensitive domain, and site-directed mutagenesis shows that the pore-lining
residue D47 is critical in determining high Mg(2+)-sensitivity. Single-channel
analysis of Mg(2+)-sensitive chimeras and mutants reveals that [Mg(2+)]i controls
the strength of electrical coupling mostly via gating mechanisms. In addition,
asymmetric transjunctional [Mg(2+)]i induces strong instantaneous rectification,
providing a novel mechanism for electrical rectification in homotypic Cx36 GJs.
We suggest that Mg(2+)-dependent synaptic plasticity of Cx36-containing
electrical synapses could underlie neuronal circuit reconfiguration via changes
in brain energy metabolism that affects neuronal levels of intracellular ATP and
[Mg(2+)]i.
PMID- 25135341
TI - FoxO1 at the nexus between fat catabolism and longevity pathways.
AB - Adipose tissue should not be considered a simple fat sink but a specialized
system that promptly and dynamically responds to variations of nutrients, to
fulfil its major role in whole-body energy homeostasis. Perturbation of energy
storage and utilization, as well as the expansion of adipose tissue during
ageing, are hallmarks of several inflammation-related metabolic disorders.
Studies using model organisms have provided significant insight into the genetic
factors and environmental conditions that influence adipose tissue function and
cause the failure of its homeostasis. It is now clear that reduced caloric intake
has a major impact on adipose tissue function and can provide a path towards
better health and the avoidance of age-related chronic diseases. An intricate and
evolutionary conserved signalling network is necessary to manage adipocyte
response to nutrients. The transcription factor FoxO1 plays a leading role in
integrating dietary conditions, insulin signalling and the down-stream response
of adipocytes to maintain metabolic balance. Here we review recent insights on
the novel role of FoxO1 in regulating lipid catabolism through the induction of
adipose triglyceride lipase (ATGL) and lysosomal lipase (Lipa) in adipocytes
during nutrient restriction. In particular, we highlight the nutrient-sensing and
hormone-independent feature of FoxO1 activity and illustrate how, by potentiating
lipid breakdown, the FoxO1 signalling cascade could induce pro-longevity adaptive
responses in adipose tissue.
PMID- 25135342
TI - Development and characterization of a hydrogel containing nitrofurazone for
antimicrobial topical applications.
AB - The goal of the research work entertained herein was the development and
characterization of a poly-(vinyl alcohol) (PVA) hydrogel cross-linked with
glutaraldehyde and impregnated with 0.2% (w/w) nitrofurazone (NTZ), for topical
applications. To verify the active principle release capability, one has
determined (i) swelling profile, (ii) in vitro release of NTZ via UV-VIS
spectrophotometry, and (iii) antimicrobial activity via exposure to the hydrogel
of ATCC strains of Staphylococcus aureus, Escherichia coli and Pseudomonas
aeruginosa. The optimized hydrogel was further characterized via scanning
electron microscopy (SEM), infrared spectroscopy with Fourier transform, moisture
content determinations and thermal analyses via thermal gravimetry (TGA).
Swelling tests revealed a mass increase from 100+/-5% up to 350+/-11%.
Incorporated NTZ displayed bactericidal activity, as expected, being released in
a linearly controlled fashion above 6 ug/mL during experiment timeframes of 14 h.
SEM analyses allowed verification of a homogeneous surface morphology, while
infrared spectra showed that NTZ did not bind strongly to the cross-linked
polymer. Furthermore, results from thermal analyses suggested a loss of thermal
stability arising from incorporation of NTZ in the hydrogel. The optimized
hydrogel exhibited characteristics with high potential for (antimicrobial)
treatment of skin lesions.
PMID- 25135343
TI - The current state of ethnic and racial disparities in cardiovascular care:
lessons from the past and opportunities for the future.
AB - Significant racial/ethnic disparities have been documented in cardiovascular
care. Although health care quality is improving for many Americans, differences
in clinical outcomes have persisted between racial/ethnic minority patients and
non-minorities, even when income, education level, and site of care are taken
into consideration. Potential causes of disparities are complex and are related
to differences in risk factor prevalence and control, use of evidence-based
procedures and medications, and social and environmental factors. Minority
patients are more likely to receive care from lower-quality health care providers
and institutions and experience more barriers to accessing care. Factors such as
stereotyping and bias in medicine are hard to quantify, but likely contribute to
differences in treatment. Recent trends suggest that some disparities are
decreasing. Opportunities for change and improvement exist for patients,
providers, and health care systems. Promising interventions, such as health
policy changes, quality improvement programs, and culturally targeted community
and clinic-based interventions offer hope that high-quality health care in the
USA can be provided to all patients.
PMID- 25135344
TI - Challenges and solutions to pre- and post-randomization subgroup analyses.
AB - Subgroup analyses are commonly performed in the clinical trial setting with the
purpose of illustrating that the treatment effect was consistent across different
patient characteristics or identifying characteristics that should be targeted
for treatment. There are statistical issues involved in performing subgroup
analyses, however. These have been given considerable attention in the literature
for analyses where subgroups are defined by a pre-randomization feature. Although
subgroup analyses are often performed with subgroups defined by a post
randomization feature--including analyses that estimate the treatment effect
among compliers--discussion of these analyses has been neglected in the clinical
literature. Such analyses pose a high risk of presenting biased descriptions of
treatment effects. We summarize the challenges of doing all types of subgroup
analyses described in the literature. In particular, we emphasize issues with
post-randomization subgroup analyses. Finally, we provide guidelines on how to
proceed across the spectrum of subgroup analyses.
PMID- 25135345
TI - Advances in primary angiitis of the central nervous system.
AB - Primary angiitis of the central nervous system (PACNS) is a rare idiopathic
inflammatory syndrome targeting the vessels of the brain and spinal cord.
Clinical presentation is variable, insidious, and non-specific; headache and
encephalopathy are the most common symptoms. Multiple strokes affecting numerous
vascular territories may be seen, and both focal and diffuse neurologic
dysfunction may be present. Cerebrospinal fluid (CSF) analysis is crucial; a
normal CSF along with normal brain parenchymal imaging carries a high negative
predictive value in excluding PACNS. The role of imaging continues to evolve, and
most patients have abnormal vascular imaging; however, the specificity of imaging
for PACNS has historically been poor. Cerebral and meningeal biopsy is a valuable
tool in confirming the diagnosis and excluding mimics. PACNS generally responds
to immunosuppressive therapy. Failure to respond should prompt evaluation for an
alternative diagnosis. Given the rarity of this disorder, exclusion of mimics
such as the reversible cerebral vasoconstriction syndromes (RCVS) and infectious
processes is essential.
PMID- 25135346
TI - The role of cardiac rehabilitation following acute coronary syndromes.
AB - Growing evidence highlights the important role of post-hospitalization care
(i.e., secondary prevention) for patients with an acute coronary syndrome (ACS).
While secondary prevention therapies are available that improve patient outcomes,
receipt of those treatments by patients is suboptimal. Cardiac
rehabilitation/secondary prevention (CR/SP) services are systematic, effective
models of care that improve delivery of preventive therapies and patient outcomes
after ACS, but unfortunately, patient participation in CR/SP has been suboptimal,
due to patient-, provider-, and system-based barriers. Systematic processes,
including automatic referral processes, help reduce these barriers and improve
CR/SP participation, along with the associated health benefits. Strength of
physician endorsement of CR/SP participation is another key step in improving
CR/SP participation and patient outcomes following ACS. Accountability measures
for CR/SP referral and enrollment, including performance measures and other
quality of care methods, may help improve CR/SP delivery. Early evidence suggests
that these measures have helped improve referral of eligible patients to CR/SP
programs.
PMID- 25135347
TI - Obstructive sleep apnea and acute coronary syndromes: etiology, risk, and
management.
AB - Obstructive sleep apnea (OSA) is characterized by upper airway collapse and
airflow reduction despite respiratory effort, resulting in intermittent hypoxia
and arousals, leading to a cascade of hemodynamic, autonomic, inflammatory, and
metabolic effects, responsible for its adverse cardiovascular effect. OSA is an
independent risk factor for cardiovascular disease, and its prevalence in
patients presenting with acute coronary syndromes is up to 69%. Furthermore, OSA
has been associated with increased risk of adverse events after an acute coronary
syndrome. Continuous positive airway pressure is considered the mainstay of
treatment of OSA and has been shown to reduce the risk of cardiovascular events.
However, the proper time to start treatment in the acute setting is unknown. A
prospective randomized clinical trial is currently underway to answer this
question.
PMID- 25135348
TI - Genetic variation at glucose and insulin trait loci and response to glucose
insulin-potassium (GIK) therapy: the IMMEDIATE trial.
AB - The mechanistic effects of intravenous glucose, insulin and potassium (GIK) in
cardiac ischemia are not well understood. We conducted a genetic sub-study of the
Immediate Myocardial Metabolic Enhancement During Initial Assessment and
Treatment in Emergency care (IMMEDIATE) Trial to explore effects of common and
rare glucose and insulin-related genetic loci on initial to 6-h and 6- to 12-h
change in plasma glucose and potassium. We identified 27 NOTCH2/ADAM30 and 8
C2CD4B variants conferring a 40-57% increase in glucose during the first 6 h of
infusion (P<5.96 * 10(-6)). Significant associations were also found for ABCB11
and SLC30A8 single-nucleotide polymorphisms (SNPs) and glucose responses, and an
SEC61A2 SNP with a potassium response to GIK. These studies identify genetic
factors that may impact the metabolic response to GIK, which could influence
treatment benefits in the setting of acute coronary syndromes (ACS).
PMID- 25135351
TI - Effects of drying methods on the preparation of dexamethasone-loaded chitosan
microspheres.
AB - The purpose of this study was to investigate the effects of drying methods on the
preparation of dexamethasone- (Dex-) loaded chitosan microspheres. Two drying
methods, namely, air drying and freeze drying, were adopted. The physical
properties of the beads were first investigated and then the loading and release
of Dex were characterized. Finally, the bioactivity of released Dex was
evaluated. The data showed that, compared with freeze-dried beads, air-dried
beads were denser and smaller, and had lower swelling ratios, slower degradation
rate and greater Rockwell hardness. In terms of drug delivery, air-dried beads
had lower encapsulation efficiency and a slower release rate of Dex. Regarding
bioactivity, both groups prompted cell differentiation without significant
differences. However, Dex released from freeze-dried beads inhibited cell
proliferation, while Dex released from air-dried beads did not. Based on these
results, we conclude that incorporation of Dex enhanced the osteogenic potential
of chitosan microspheres and drying methods did affect the physical properties of
the chitosan microspheres, which further influenced the drug loading and release.
At the moment, the air-drying method is more appropriate to prepare Dex-loaded
chitosan microspheres.
PMID- 25135349
TI - The synaptoneurosome transcriptome: a model for profiling the emolecular effects
of alcohol.
AB - Chronic alcohol consumption changes gene expression, likely causing persistent
remodeling of synaptic structures via altered translation of mRNAs within
synaptic compartments of the cell. We profiled the transcriptome from
synaptoneurosomes (SNs) and paired total homogenates (THs) from mouse amygdala
following chronic voluntary alcohol consumption. In SN, both the number of
alcohol-responsive mRNAs and the magnitude of fold-change were greater than in
THs, including many GABA-related mRNAs upregulated in SNs. Furthermore, SN gene
co-expression analysis revealed a highly connected network, demonstrating
coordinated patterns of gene expression and highlighting alcohol-responsive
biological pathways, such as long-term potentiation, long-term depression,
glutamate signaling, RNA processing and upregulation of alcohol-responsive genes
within neuroimmune modules. Alterations in these pathways have also been observed
in the amygdala of human alcoholics. SNs offer an ideal model for detecting
intricate networks of coordinated synaptic gene expression and may provide a
unique system for investigating therapeutic targets for the treatment of
alcoholism.
PMID- 25135352
TI - Field dependence-independence modulates the efficiency of filtering out
irrelevant information in a visual working memory task.
AB - Past research has demonstrated that field dependence-independence (FDI) can
affect academic performance, selective attention, and working memory. However,
the underlying mechanism of how FDI modulates selective attention and working
memory is still unclear. Using event-related potential (ERP) techniques,
specifically with the contralateral delay activity (CDA), the present study found
that the correct response rates and CDA amplitudes in the 2-item and 2-item-2
distractor conditions were comparable for field independence (FI) participants.
Field dependence (FD) participants performed worse, and the CDA amplitude was
enhanced when distractors appeared. These results indicated that FI participants
can filter out task-irrelevant information more efficiently than FD participants.
The main difference between FD and FI individuals is their inhibition function.
PMID- 25135353
TI - Frequency-dependent signal processing in apical dendrites of hippocampal CA1
pyramidal cells.
AB - Depending on an animal's behavioral state, hippocampal CA1 pyramidal cells
receive distinct patterns of excitatory and inhibitory synaptic inputs. The time
dependent changes in the frequencies of these inputs and the nonuniform
distribution of voltage-gated channels lead to dynamic fluctuations in membrane
conductance. In this study, using a whole-cell patch-clamp method, we attempted
to record and analyze the frequency dependencies of membrane responsiveness in
Wistar rat hippocampal CA1 pyramidal cells following noise current injection
directly into dendrites and somata under pharmacological blockade of all synaptic
inputs. To estimate the frequency-dependent properties of membrane potential,
membrane impedance was determined from the voltage response divided by the input
current in the frequency domain. The cell membrane of most neurons showed low
pass filtering properties in all regions. In particular, the properties were
strongly expressed in the somata or proximal dendrites. Moreover, the data
revealed nonuniform distribution of dendritic impedance, which was high in the
intermediate segment of the apical dendritic shaft (~220-260MUm from the soma).
The low-pass filtering properties in the apical dendrites were more enhanced by
membrane depolarization than those in the somata. Coherence spectral analysis
revealed high coherence between the input signal and the output voltage response
in the theta-gamma frequency range, and large lags emerged in the distal
dendrites in the gamma frequency range. Our results suggest that apical dendrites
of hippocampal CA1 pyramidal cells integrate synaptic inputs according to the
frequency components of the input signal along the dendritic segments receiving
the inputs.
PMID- 25135350
TI - Folic acid supplementation in pregnancy and implications in health and disease.
AB - Maternal exposure to dietary factors during pregnancy can influence embryonic
development and may modulate the phenotype of offspring through epigenetic
programming. Folate is critical for nucleotide synthesis, and preconceptional
intake of dietary folic acid (FA) is credited with reduced incidences of neural
tube defects in infants. While fortification of grains with FA resulted in a
positive public-health outcome, concern has been raised for the need for further
investigation of unintended consequences and potential health hazards arising
from excessive FA intakes, especially following reports that FA may exert
epigenetic effects. The objective of this article is to discuss the role of FA in
human health and to review the benefits, concerns and epigenetic effects of
maternal FA on the basis of recent findings that are important to design future
studies.
PMID- 25135354
TI - Phosphorylation enhances recombinant HSP27 neuroprotection against focal cerebral
ischemia in mice.
AB - Heat shock protein 27 (HSP27) exerts cytoprotection against many cellular insults
including cerebral ischemia. We previously indicated that intravenous injection
of HSP27 purified from human lymphocytes (hHSP27) significantly reduced infarct
volume following cerebral ischemia-reperfusion injury, while recombinant HSP27
(rHSP27) was less effective. Phosphorylation is important for HSP27 function, and
hHSP27 was more highly phosphorylated than rHSP27. We hypothesized that MAPKAP
kinase 2 in vitro-phosphorylated rHSP27 (prHSP27) might increase its brain
protection. Mice underwent transient 1-h middle cerebral artery occlusion (MCAO),
and then received tail-vein injections of one of the following 1h after
reperfusion: hHSP27 as positive control, rHSP27, prHSP27, or bovine serum albumin
(BSA) as control. We measured infarct volume, neurological deficits, neurological
severity, physiological parameters, cell-death, oxidative stress, and
inflammatory response. Compared with BSA controls (30.7+/-3.1mm(3), n=5), infarct
volume was reduced by 67% in the hHSP27 positive-control group (10.1+/-4.6mm(3),
P<0.001, n=5), 17% following rHSP27 (25.4+/-3.6mm(3), P<0.05, n=5), and 46%
following prHSP27 (16.5+/-4.0mm(3), P<0.001, n=9). Compared to the rHSP27 and BSA
treated groups, prHSP27 also reduced functional deficits, and significantly
suppressed apoptosis, oxidative stress, and inflammatory responses. Here, we
showed the superior neuroprotective effects of phosphorylated HSP27 by
administering prHSP27. prHSP27 may be a useful therapeutic agent to protect
against acute cerebral ischemic stroke.
PMID- 25135355
TI - Down-regulation of PPARalpha in the spinal cord contributes to augmented
peripheral inflammation and inflammatory hyperalgesia in diet-induced obese rats.
AB - Obesity is associated with augmented peripheral inflammation and pain sensitivity
in response to inflammatory stimulation, but the underlying mechanisms remain
unclear. Emerging evidence has shown that activation of peroxisome proliferator
activated receptor-alpha (PPARalpha) in the central nervous system controls
peripheral inflammation and pain. We hypothesized that obesity might down
regulate PPARalpha in the spinal cord, leading to enhanced peripheral
inflammation and inflammatory hyperalgesia. Sprague-Dawley rats fed a high-fat
diet (HF) for 12weeks developed metabolic disorder and displayed significantly
decreased spinal PPARalpha expression and activity. Interestingly,
intracerebroventricular (ICV) infusion of the PPARalpha activator
palmitoylethanolamide (PEA) in HF-fed rats for 2weeks normalized spinal PPARalpha
expression and activity without altering metabolic parameters. HF-fed rats were
more sensitive to stimulation of the inflamed paw, and exhibited more severe paw
edema following carrageenan injection, whereas HF-fed rats receiving ICV PEA had
similar pain sensitivity and paw edema to LF-fed rats. No difference in the
expression of inflammatory mediators or nuclear factor (NF)-kappaB activity was
observed at baseline among groups. Carrageenan induced decreased PPARalpha
expression and activity, increased spinal cord inflammatory mediator expression
and NF-kappaB activity in both LF-and HF-fed rats. However, the increase was more
pronounced in HF-fed rats and corrected by PEA. Intrathecal injection of small
interfering RNA (siRNA) against PPARalpha in HF-fed rats completely abolished PEA
effects on peripheral pain sensitivity and paw edema. These findings suggest that
diet-induced obesity causes down-regulation of spinal PPARalpha, which
facilitates the susceptibility to peripheral inflammatory challenge by increasing
inflammatory response in the spinal cord, contributing to augmented peripheral
inflammation and inflammatory hyperalgesia in obesity.
PMID- 25135356
TI - Loudness modulation after transient and permanent hearing loss: implications for
tinnitus and hyperacusis.
AB - Loudness is the primary perceptual correlate of sound intensity. The relationship
between sound intensity and loudness is not fixed, and can be modified by short
term sound deprivation or stimulation. Deprivation increases sound sensitivity,
whereas stimulation decreases it. We review the effects of short-term auditory
deprivation and stimulation on the auditory central nervous system of humans and
animals, and we extend the discussion to permanent auditory deprivation (hearing
loss) and auditory pathologies of loudness perception. Although there is
sufficient evidence to conclude that loudness can be modulated in normal hearing
listeners by temporary sound deprivation and stimulation, evidence is scanter for
the hearing-impaired listeners. In addition, cortical effects of sound
deprivation and stimulation in humans, which may correlate with loudness coding,
are still largely unknown and should be the target of future research.
PMID- 25135357
TI - Mechanisms and targets of the modulatory action of S-nitrosoglutathione (GSNO) on
inflammatory cytokines expression.
AB - A number of experimental studies has documented that S-nitrosoglutathione (GSNO),
the main endogenous low-molecular-weight S-nitrosothiol, can exert modulatory
effects on inflammatory processes, thus supporting its potential employment in
medicine for the treatment of important disease conditions. At molecular level,
GSNO effects have been shown to modulate the activity of a series of
transcription factors (notably NF-kappaB, AP-1, CREB and others) as well as other
components of signal transduction chains (e.g. IKK-beta, caspase 1, calpain and
others), resulting in the modulation of several cytokines and chemokines
expression (TNFalpha, IL-1beta, IFN-gamma, IL-4, IL-8, RANTES, MCP-1 and others).
Results reported to date are however not univocal, and a single main mechanism of
action for the observed anti-inflammatory effects of GSNO has not been
identified. Conflicting observations can be explained by differences among the
various cell types studies as to the relative abundance of enzymes in charge of
GSNO metabolism (GSNO reductase, gamma-glutamyltransferase, protein disulfide
isomerase and others), as well as by variables associated with the individual
experimental models employed. Altogether, anti-inflammatory properties of GSNO
seem however to prevail, and exploration of the therapeutic potential of GSNO and
analogues appears therefore warranted.
PMID- 25135358
TI - Autosomal recessive limb-girdle muscular dystrophies in the Czech Republic.
AB - BACKGROUND: Autosomal recessive limb-girdle muscular dystrophies (LGMD2) include
a number of disorders with heterogeneous etiology that cause predominantly
weakness and wasting of the shoulder and pelvic girdle muscles. In this study, we
determined the frequency of LGMD subtypes within a cohort of Czech LGMD2 patients
using mutational analysis of the CAPN3, FKRP, SGCA, and ANO5 genes. METHODS: PCR
sequencing analysis; sequence capture and targeted resequencing. RESULTS:
Mutations of the CAPN3 gene are the most common cause of LGMD2, and mutations in
this gene were identified in 71 patients in a set of 218 Czech probands with a
suspicion of LGMD2. Totally, we detected 37 different mutations of which 12 have
been described only in Czech LGMD2A patients. The mutation c.550delA is the most
frequent among our LGMD2A probands and was detected in 47.1% of CAPN3 mutant
alleles. The frequency of particular forms of LGMD2 was 32.6% for LGMD2A (71
probands), 4.1% for LGMD2I (9 probands), 2.8% for LGMD2D (6 probands), and 1.4%
for LGMD2L (3 probands).Further, we present the first results of a new approach
established in the Czech Republic for diagnosis of neuromuscular diseases:
sequence capture and targeted resequencing. Using this approach, we identified
patients with mutations in the DYSF and SGCB genes. CONCLUSIONS: We characterised
a cohort of Czech LGMD2 patients on the basis of mutation analysis of genes
associated with the most common forms of LGMD2 in the European population and
subsequently compared the occurrence of particular forms of LGMD2 among countries
on the basis of our results and published studies.
PMID- 25135359
TI - Ethnomedicinal and phytochemical review of Pakistani medicinal plants used as
antibacterial agents against Escherichia coli.
AB - Medicinal plants have always been part of human culture and have the potential to
cure different diseases caused by microorganisms. In Pakistan, biologists are
mainly focusing on plants' antimicrobial activities against Escherichia coli due
to its increasing resistance to antibiotics. In total, extracts from 34
ethnomedicinally valuable Pakistani plants were reported for in-vitro anti-E.
coli activities. Mostly methanolic extracts of medicinal plants were used in
different studies, which have shown comparatively higher inhibitory activities
against E. coli than n-hexane and aqueous extracts. It has been found that
increasing concentration (mg/ml) of methanolic extract can significantly increase
(p<0.01) anti-E. coli activities. Not all medicinal plants are extracted in
solvents others than above, which should also be tested against E. coli.
Moreover, medicinal plant species must be fully explored phytochemically, which
may lead to the development of new drugs.
PMID- 25135361
TI - Interaction of Leukocyte Elastase Inhibitor/L-DNase II with BCL-2 and BAX.
AB - Leukocyte Elastase Inhibitor (LEI, also called serpin B1) is a protein involved
in apoptosis among other physiological processes. We have previously shown that
upon cleavage by its cognate protease, LEI is transformed into L-DNase II, a
protein with a pro-apoptotic activity. The caspase independent apoptotic pathway,
in which L-DNase II is the final effector, interacts with other pro-apoptotic
molecules like Poly-ADP-Ribose polymerase (PARP) or Apoptosis Inducing Factor
(AIF). The screening of LEI/L-DNase II interactions showed a possible interaction
with several members of the BCL-2 family of proteins which are known to have a
central role in the regulation of caspase dependent cell death. In this study, we
investigated the regulation of LEI/L-DNase II pathway by two members of this
family of proteins: BAX and BCL-2, which have opposite effects on cell survival.
We show that, in both BHK and HeLa cells, LEI/L-DNase II can interact with BCL-2
and BAX in apoptotic and non-apoptotic conditions. These proteins which are
usually thought to be anti-apoptotic and pro-apoptotic respectively, both inhibit
the L-DNase II pro-apoptotic activity. These results give further insight in the
regulation of caspase independent pathways and highlight the involvement of the
intracellular environment of a given protein in the determinism of its function.
They also add a link between caspase-dependent and independent pathways of
apoptosis.
PMID- 25135362
TI - Ubiquitin proteasome system-mediated degradation of synaptic proteins: An update
from the postsynaptic side.
AB - The ubiquitin proteasome system is one of the principle mechanisms for the
regulation of protein homeostasis in mammalian cells. In dynamic cellular
structures such as neuronal synapses, ubiquitin proteasome system and protein
translation provide an efficient way for cells to respond promptly to local
stimulation and regulate neuroplasticity. The majority of research related to
long-term plasticity has been focused on the postsynapses and has shown that
ubiquitination and subsequent degradation of specific proteins are involved in
various activity-dependent plasticity events. This review summarizes recent
achievements in understanding ubiquitination of postsynaptic proteins and its
impact on synapse plasticity and discusses the direction for advancing future
research in the field.
PMID- 25135360
TI - "Fast track" rehabilitation after gastric cancer resection: experience with 80
consecutive cases.
AB - BACKGROUND: To evaluate the safety, efficacy and outcomes of fast-track
rehabilitation applied to gastric cancer proximal, distal and total gastrectomy.
METHODS: Eighty consecutive patients undergoing gastric cancer resection
performed by a single surgeon, received perioperative multimodal rehabilitation.
Demographic and operative data, gastrointestinal function, postoperative hospital
stays, surgical and general complications and mortality were assessed
prospectively. RESULTS: Of the 80 patients (mean age 56.3 years), 10 (12.5%)
received proximal subtotal gastrectomy (Billroth I), 38 (47.5%) received distal
(Billroth II), and 32 (40%) received total gastrectomy (Roux-en-Y). Mean
operative time was 104.9 minutes and intraoperative blood loss was 281.9 ml. Time
to first flatus was 2.8 +/- 0.5 postoperative days. Patients were discharged at a
mean of 5.3 +/- 2.2 postoperative days; 30-day readmission rate was 3.8%. In
hospital mortality was 0%; general and surgical complications were both 5%.
CONCLUSIONS: Fast-track multimodal rehabilitation is feasible and safe in
patients undergoing gastric cancer resection and may reduce time to first flatus
and postoperative hospital stays.
PMID- 25135363
TI - Aerobic granular sludge mediated biodegradation of an organophosphorous ester,
dibutyl phosphite.
AB - Dibutyl phosphite, an organophosphorous compound, finds applications in different
chemical industries and processes. Here, we report an efficient approach of
biodegradation to be eventually used in bioremediation of dibutyl phosphite.
Aerobic granules capable of dibutyl phosphite biodegradation were cultivated in a
sequencing batch reactor (SBR). The SBR was operated with a 24-h cycle by feeding
with dibutyl phosphite as a cosubstrate along with acetate. During the course of
the SBR operation, aerobic granules of 0.9 +/- 0.3 mm size were developed.
Complete biodegradation of 1.4, 2 and 3 mM of dibutyl phosphite was achieved in
4, 5 and 8 h, respectively, accompanied by stoichiometric release of phosphite
(H3 PO3). Phosphatase activity in the dibutyl phosphite-degrading granular
biomass was 3- and 1.5-fold higher as compared to the activated sludge (seed
biomass) and acetate-fed aerobic granules, respectively, indicating involvement
in the hydrolysis of dibutyl phosphite. Microbial community analysis by t-RFLP
showed the presence of 12 different bacterial types. Two bacterial strains
capable of growth on dibutyl phosphite as sole carbon source were isolated and
characterized as Acidovorax sp. and Sphingobium sp. The results show that aerobic
microbial granules based process is suitable for the treatment of dibutyl
phosphite contaminated water.
PMID- 25135364
TI - Left ventricular remodeling after acute myocardial infarction: the influence of
viability and revascularization - an echocardiographic substudy of the VIAMI
trial.
AB - BACKGROUND: Viability seems to be important in preventing ventricular remodeling
after acute myocardial infarction (AMI). We investigated the influence of
viability, as demonstrated with low-dose dobutamine echocardiography, and the
role of early revascularization on the process of left ventricular (LV)
remodeling after AMI. METHODS: We retrospectively investigated 224 patients who
were initially included in the viability-guided angioplasty after acute
myocardial infarction-trial (VIAMI-trial). Patients in the VIAMI-trial did not
undergo a primary or rescue percutaneous coronary intervention and were stable in
the early in-hospital phase. Patients underwent viability testing within 72 hours
after AMI. Patients with viability were randomized to an invasive strategy or an
ischemia-guided strategy. Follow-up echocardiography was performed at a mean of
205 days. In this echocardiographic substudy, patients were divided into three
new groups: group 1, viable and revascularized before follow-up echocardiogram;
group 2, viable, but medically treated; and group 3, non-viable patients.
RESULTS: Group 1 showed preservation of LV volume indices. The ejection fraction
(EF) increased significantly from 54.0% to 57.5% (P = 0.047). Group 2 showed a
significant increase in LV volume indices with no improvement in EF (53.3% versus
53.0%, P = 0.86). Group 3 showed a significant increase in LV volume indices,
with a decrease in EF from 53.5% to 49.1% (P = 0.043). Multivariate logistic
regression analysis indicated the number of viable segments and revascularization
during follow-up as independent predictors for EF improvement, especially in
patients with lower EF at baseline. CONCLUSION: Viability early after AMI is
associated with improvement in LV function after revascularization. When viable
myocardium is not revascularized, the LV tends to remodel with increased LV
volumes, without improvement of EF. Absence of viability results in ventricular
dilatation and deterioration of EF, irrespective of revascularization status.
TRIAL REGISTRATION: NCT00149591 (assigned: 6 September 2005).
PMID- 25135365
TI - Topics of internal medicine for undergraduate dental education: a qualitative
study.
AB - INTRODUCTION: Due to the ageing population, internal medicine has become
increasingly important for dental education. Although several studies have
reported dentists' dissatisfaction with their internal medicine training, no
guidelines exist for internal medicine learning objectives in dental education.
The aim of this study was to identify topics of internal medicine considered to
be relevant for dental education by dentists and internists. METHODS: Eight
dentists from private dental practices in Hamburg and eight experienced internal
medicine consultants from Hamburg University Hospital were recruited for semi
structured interviews about internal medicine topics relevant for dentists.
Internal diseases were clustered into representative subspecialties. Dentists and
internists were also asked to rate medical diseases or emergencies compiled from
the literature by their relevance to dental education. RESULTS: Coagulopathy and
endocarditis were rated highest by dentists, whilst anaphylaxis was rated highest
by internists. Dentists rated hepatitis, HIV, organ transplantation and head/neck
neoplasm significantly higher than internists. The largest number of different
internal diseases mentioned by dentists or internists could be clustered under
cardiovascular diseases. The number of specific diseases dentists considered to
be relevant for dental education was higher in the subspecialties cardiovascular
diseases, haematology/oncology and infectiology. CONCLUSION: We identified the
internal medicine topics most relevant for dental education by surveying
practising dentists and internists. The relevance of these topics should be
confirmed by larger quantitative studies to develop guidelines how to design
specific learning objectives for internal medicine in the dental curriculum.
PMID- 25135366
TI - Gastrointestinal cancer: FOLFIRI plus cetuximab--preferred first-line treatment
for mCRC.
PMID- 25135368
TI - Breast cancer: Subclones-go forth and mutate.
PMID- 25135369
TI - Breast cancer: PALB2--a new player in hereditary breast cancer.
PMID- 25135367
TI - Precision therapy for lymphoma--current state and future directions.
AB - Modern advances in genomics and cancer biology have produced an unprecedented
body of knowledge regarding the molecular pathogenesis of lymphoma. The diverse
histological subtypes of lymphoma are molecularly heterogeneous, and most likely
arise from distinct oncogenic mechanisms. In parallel to these advances in
lymphoma biology, several new classes of molecularly targeted agents have been
developed with varying degrees of efficacy across the different types of
lymphoma. In general, the development of new drugs for treating lymphoma has been
mostly empiric, with a limited knowledge of the molecular target, its involvement
in the disease, and the effect of the drug on the target. Thus, the variability
observed in clinical responses likely results from underlying molecular
heterogeneity. In the era of personalized medicine, the challenge for the
treatment of patients with lymphoma will involve correctly matching a molecularly
targeted therapy to the unique genetic and molecular composition of each
individual lymphoma. In this Review, we discuss current and emerging biomarkers
that can guide treatment decisions for patients with lymphoma, and explore the
potential challenges and strategies for making biomarker-driven personalized
medicine a reality in the cure and management of this disease.
PMID- 25135371
TI - Impact of osteoid osteomas of the hip on the size and fatty infiltration of the
thigh muscles.
AB - We aimed to assess the impact of osteoid osteomas of the hip on the size and
fatty infiltration of the muscle thigh in 42 patients. The thigh circumference,
cross-sectional areas, and fatty atrophy of four anterior muscles were assessed
on magnetic resonance axial T1-weighted images. A significant fatty atrophy was
found in the studied muscles of the ipsilateral thigh except for the rectus
femoris. No significant association was demonstrated with pain duration
suggesting that muscle atrophy may rather be related to the locoregional
inflammation than subsequent to the disuse of the limb.
PMID- 25135370
TI - An economic evaluation of maxillary implant overdentures based on six vs. four
implants.
AB - BACKGROUND: The purpose of the present study was to assess the value for money
achieved by bar-retained implant overdentures based on six implants compared with
four implants as treatment alternatives for the edentulous maxilla. METHODS: A
Markov decision tree model was constructed and populated with parameter estimates
for implant and denture failure as well as patient-centred health outcomes as
available from recent literature. The decision scenario was modelled within a ten
year time horizon and relied on cost reimbursement regulations of the German
health care system. The cost-effectiveness threshold was identified above which
the six-implant solution is preferable over the four-implant solution.
Uncertainties regarding input parameters were incorporated via one-way and
probabilistic sensitivity analysis based on Monte-Carlo simulation. RESULTS:
Within a base case scenario of average treatment complexity, the cost
effectiveness threshold was identified to be 17,564 ? per year of denture
satisfaction gained above of which the alternative with six implants is
preferable over treatment including four implants. Sensitivity analysis yielded
that, depending on the specification of model input parameters such as patients'
denture satisfaction, the respective cost-effectiveness threshold varies
substantially. CONCLUSIONS: The results of the present study suggest that bar
retained maxillary overdentures based on six implants provide better patient
satisfaction than bar-retained overdentures based on four implants but are
considerably more expensive. Final judgements about value for money require more
comprehensive clinical evidence including patient-centred health outcomes.
PMID- 25135372
TI - Pregnancy outcomes of mothers with an alcohol-related diagnosis: a population
based cohort study for the period 1983-2007.
AB - OBJECTIVE: To examine fetal outcomes of mothers with an alcohol-related
diagnosis. DESIGN: Population-based cohort. SETTING: Western Australia (WA).
POPULATION: Births on the WA Midwives Notification System (1983-2007). METHODS:
Infants of mothers with an alcohol-related diagnosis [International
Classification of Disease (ICD), 9th/10th revisions] recorded on WA health data
sets (non-Aboriginal n = 13 807; Aboriginal n = 9766) were identified through the
WA data linkage system. A comparison cohort of infants born to mothers without an
alcohol diagnosis was frequency matched on maternal age, year of birth of the
offspring, and Aboriginal status (non-Aboriginal n = 40 148; Aboriginal n = 20
643). MAIN OUTCOME MEASURES: Poisson regression-generated adjusted relative risk
(aRR) and 95% confidence intervals (95% CIs) for small for gestational age (SGA),
preterm birth, and low-Apgar score, calculated separately for non-Aboriginal and
Aboriginal infants of mothers with an alcohol diagnosis recorded during pregnancy
and any alcohol diagnosis. Population-attributable fractions were calculated.
RESULTS: The aRR for non-Aboriginal infants when a maternal alcohol diagnosis was
recorded during pregnancy ranged from 1.79 (95% CI 1.42-2.16) for SGA to 2.57
(95% CI 1.69-4.27) for preterm birth <32 weeks of gestation, and for Aboriginal
infants ranged from 2.69 (95% CI 2.28-3.16) to 1.99 (95% CI 1.40-2.84),
respectively. The highest population-attributable fractions were for any alcohol
diagnosis and for Aboriginal infants. For Aboriginal births, approximately 9%
(95% CI 4.74-12.97) and 10.1% (95% CI 5.50-14.49) of moderate and very preterm
births, respectively, and 24.4% (95% CI 13.5-21.2%) of SGAs were attributable to
having a mother with any alcohol-related diagnosis. CONCLUSIONS: Mothers with an
alcohol diagnosis are at increased risk of poor pregnancy outcomes. The public
health impact of maternal alcohol-use disorders on fetal outcomes is significant.
PMID- 25135374
TI - [Hyperostosis of the internal auditory canal : An incidental finding?].
AB - In contrast to the fairly common exostoses in the external auditory canal,
hyperostoses and osteomas of the internal auditory canal are extremely rare. In
this case report we present a patient with sudden right-sided sensorineural
hearing loss, in whom imaging revealed hyperostosis with bilateral stenosis of
the internal auditory canal. Whether the connection of such radiological findings
with dysfunction of cranial nerves VII and VIII be causal or coincidental is
controversially discussed in the literature. Therefore, the indication for
surgical intervention should be considered with extreme caution. Despite
examination of our radiology database comprising almost 1000 MRI/CT temporal bone
investigations, we could find no other cases of hyperostosis of the petrous bone.
This case thus represents a rare disease, which should be considered a
differential diagnosis.
PMID- 25135373
TI - [How reliable are non-instrumental assessment tools for dysphagia?].
AB - BACKGROUND: The requirement for otorhinolaryngologists and phoniatricians to
diagnose dysphagia and evaluate its extent is on the rise, particularly in light
of demographic changes. The gold standards in confirmatory diagnostics are
fiberoptic endoscopic evaluation of swallowing (FEES) and the videofluoroscopic
swallowing examination (VFS). Standardized assessments, such as questionnaires or
assessments involving probatory swallows are often applied as screening or
supportive measures. This article aims to give a critical overview of the
assessment tools frequently used in clinical routine. Test quality is assessed,
particularly compared to FEES and VFS. METHODS: A selective literature search
using PubMed has been conducted. RESULTS: On the basis of this lierature search,
48 assessment tools were identified. These can be classified into screening
tools, instrument-based tools (implementation standards and evaluation protocols)
and questionnaire-based assessment inventories. DISCUSSION: In order to diagnose
and evaluate dysphagia on the basis of assessment critieria, clinicians should be
aware of indications for, as well as the advantages, disadvantages and test
quality of the assessment tools. Considering the different assessment tools for
anamnesis and probatory swallowing, rather low sensitivities and specificities
for possible penetration and aspiration are evident. In cases where these
symptoms of dysphagia are not evident and reliably assessable, confirmatory
assessment via FEES or VFS is essential.
PMID- 25135375
TI - [Olfactory function in old age].
AB - Olfactory function decreases with age. This is frequent: one in four individuals
above 52 years of age exhibits olfactory loss. This decrease in olfactory
function can be seen at all levels of olfactory information processing, both on a
functional and a morphological level. Recent studies, however, indicate that
olfactory loss with age may not be an inevitable fate.
PMID- 25135376
TI - Associations among late chronotype, body mass index and dietary behaviors in
young adolescents.
AB - BACKGROUND/OBJECTIVES: Levels of pediatric obesity continue to rise. Previous
evidence has linked short sleep duration and/or poor sleep quality to obesity
development, although objective data are limited. As adolescents transition
through puberty, circadian shifts occur, resulting in sleep loss. However, little
is known whether chronotype is associated with body mass index (BMI) or dietary
behaviors in adolescents. We hypothesized late chronotype would be positively
associated with BMI and poorer dietary behaviors. SUBJECTS/METHODS: A total of
511 UK young adolescents (11-13 years) from eight secondary schools across the
Midlands region (UK) participated in the Midlands Adolescent Schools Sleep
Education Study (MASSES), a cross-sectional study to assess potential
relationships between chronotype and BMI z-score as well as dietary habits.
Height (cm) and weight (kg) were objectively measured for BMI calculation and
participants completed a questionnaire to assess dietary habits. A subsample of
236 adolescents wore wrist actigraphy for 7 days to estimate average sleep
duration (weekday, weekend and combined) and sleep efficiency. RESULTS:
Definitely evening chronotype was positively associated with BMI z-score compared
to definitely morning chronotypes beta = 0.51, P < 0.01, after adjustment. Higher
frequency of consuming unhealthy snacks, night-time caffeine consumption and
inadequate daily intake of fruit/vegetables were also associated with later
chronotype (all P ? 0.01). Actigraphy estimated sleep duration was an independent
predictor of BMI z-score beta = -0.36, P < 0.001. Sleep efficiency did not
predict BMI z-score after adjustment, beta = -0.03, P = 0.07. CONCLUSIONS: Later
chronotype young adolescents are at risk of increased BMI and poorer dietary
behaviors. Although short sleep duration, but not sleep efficiency, was also an
independent risk factor for increased BMI, different mechanisms may be driving
the late chronotype and shorter sleep duration associations with BMI in this age
group. Sleep hygiene education may help adolescents to better understand the
impact of sleeping habits on physical health.
PMID- 25135377
TI - Does the FTO gene interact with the socioeconomic status on the obesity
development among young European children? Results from the IDEFICS study.
AB - BACKGROUND: Various twin studies revealed that the influence of genetic factors
on psychological diseases or behaviour is more expressed in socioeconomically
advantaged environments. Other studies predominantly show an inverse association
between socioeconomic status (SES) and childhood obesity in Western developed
countries. The aim of this study is to investigate whether the fat mass and
obesity-associated (FTO) gene interacts with the SES on childhood obesity in a
subsample (N = 4406) of the IDEFICS (Identification and prevention of Dietary-
and lifestyle-induced health EFfects In Children and infantS) cohort. METHODS: A
structural equation model (SEM) is applied with the latent constructs obesity,
dietary intakes, physical activity and fitness habits, and parental SES to
estimate the main effects of the latter three variables and a FTO polymorphism on
childhood obesity. Further, a multiple group SEM is used to explore whether an
interaction effect exists between the single nucleotide polymorphism rs9939609
within the FTO gene and SES. RESULTS: Significant main effects are shown for
physical activity and fitness (standardised [betacrc ](s) = -0.113), SES
([betacrc ](s) = -0.057) and the FTO homozygous AA risk genotype ([betacrc ](s) =
-0.177). The explained variance of obesity is ~9%. According to the multiple
group approach of SEM, we see an interaction between SES and FTO with respect to
their effect on childhood obesity (Deltachi(2) = 7.3, df = 2, P = 0.03).
CONCLUSION: Children carrying the protective FTO genotype TT seem to be more
protected by a favourable social environment regarding the development of obesity
than children carrying the AT or AA genotype.
PMID- 25135378
TI - Analysis of patients with atypical hemolytic uremic syndrome treated at the Mie
University Hospital: concentration of C3 p.I1157T mutation.
AB - Atypical hemolytic uremic syndrome (aHUS) is caused by abnormalities of the
complement system and has a significantly poor prognosis. The clinical phenotypes
of 12 patients in nine families with aHUS with familial or recurrent onset and
ADAMTS13 activity of >=20 % treated at the Mie University Hospital were examined.
In seven of the patients, the first episode of aHUS occurred during childhood and
ten patients experienced a relapse. All patients had renal dysfunction and three
had been treated with hemodialysis. Seven patients experienced probable
triggering events including common cold, influenza, bacterial infection and/or
vaccination for influenza. All patients had entered remission, and renal function
was improved in 11 patients. DNA sequencing of six candidate genes, identified a
C3 p.I1157T missense mutation in all eight patients in six families examined and
this mutation was causative for aHUS. A causative mutation THBD p.D486Y was also
identified in an aHUS patient. Four missense mutations, CFH p.V837I, p.Y1058H,
p.V1060L and THBD p.R403K may predispose to aHUS manifestation; the remaining
seven missense mutations were likely neutral. In conclusion, the clinical
phenotypes of aHUS are various, and there are often trigger factors. The C3
p.I1157T mutation was identified as the causative mutation for aHUS in all
patients examined, and may be geographically concentrated in or around the Mie
prefecture in central Japan.
PMID- 25135379
TI - University Gynaecology and Obstetrics, quo vadis? A Department of Women's Health
University Women's Hospital of the future?
AB - PURPOSE: Numerous changes in society, science and health care challenge
gynaecology and obstetrics. These challenges include the maintenance of
excellence in research, commercial potential and clinical innovation, as well as
the maintenance of adequate human resources, new standards for patient
orientation and individualised medicine. METHODS: Based on a SWOT analysis of the
status quo, of local and national quality data, a search regarding national
conceptions and of international best practice for women's health centres, the
model of a Department of Women's Health was developed. RESULTS: The Department,
consisting of a University Hospital and a Research Institute, should interlink
clinical care and science. With the establishment of the department, a pool of
expertise is achieved which encompasses gynaecology and obstetrics from basic
care to the high-technology segments, as well as all the scientific areas
relevant to the medical discipline and women's health, including health services
research. Preservation and attraction of personnel resources are based on the
department's excellence, on reliable perspectives and the flexibility of job
profiles, which also result from the close connection between care and research
and the expansion of perspectives on women's health. CONCLUSIONS: Methodological
diversity and inter-professionalism build the appropriate base for the further
development of research fields. At the same time, the Department creates space
for the consolidation of the core areas and the integration of sub-disciplines
(clinical and scientific) to maintain the unity of this discipline. Via the
scientific monitoring of the implementation, suitable elements can be highlighted
for transfer to other facilities.
PMID- 25135380
TI - Relationship between first trimester visualization of the intracranial
translucency and spina bifida.
AB - PURPOSE: To establish a reference range for the intracranial translucency (IT).
METHODS: In this prospective study, we examined 596 singleton fetuses at 11-14
weeks of gestation using transabdominal ultrasonography. The distribution curves
of the anterior-posterior diameter of the IT were established according to the
gestational weeks, and the percentiles for 11-14 weeks of gestation were
calculated. Regression analysis was performed to estimate the relationship
between the anterior-posterior diameter of the IT and other fetal biometric
parameters. RESULTS: The mean anterior-posterior diameter of the IT was 1.8 +/-
0.4 mm. From 11 to 14 weeks of gestation, the IT diameter increased linearly with
advancing gestation. The linear regression equation for the IT * crown-rump
length (CRL) was IT = CRL * 0.0184 + 0.575 (R = 0.385, p < 0.001). The linear
regression equation for the IT * biparietal diameter (BPD) was IT = BPD * 0.0532
+ 0.632 (R = 0.346, p < 0.001). The linear regression equation for IT *
gestational age (days) (GA) was ICT = GA * 0.024 - 0.339 (R = 0.25, p < 0.001).
The linear regression analysis revealed significant correlations of the IT with
CRL, BPD, and GA. CONCLUSION: The IT increases linearly with increasing CRL, BPD,
gestational age in weeks, and gestational age in days.
PMID- 25135381
TI - Modest cooling therapies (35oC to 37.5oC) for traumatic brain injury.
AB - BACKGROUND: Animal models of traumatic brain injury suggest that induced
normothermia (36.5 or 37 oC), compared to induced hyperthermia (39 oC), improves
histopathological and neurobehavioural outcomes. Observational clinical studies
of patients with TBI suggest an association between raised body temperature and
unfavourable outcome, although this relationship is inconsistent. OBJECTIVES: To
assess the effects of modest cooling therapies (defined as any drug or physical
therapy aimed at maintaining body temperature between 35 oC and 37.5 oC) when
applied to patients in the first week after traumatic brain injury. SEARCH
METHODS: The most recent search was run on 23(rd) September 2013. We searched the
Cochrane Injuries Group's Specialised Register, The Cochrane Library (CENTRAL),
MEDLINE (OvidSP), Embase (OvidSP), ISI WOS: SCI-EXPANDED (1970) & CPCI-S (1990),
PubMed and trials registries together with reference checking. SELECTION
CRITERIA: All completed randomised, controlled and placebo-controlled trials
published or unpublished, where modest cooling therapies were applied in the
first week after traumatic brain injury. DATA COLLECTION AND ANALYSIS: Two
authors independently applied the selection criteria to relevant trials. MAIN
RESULTS: We were unable to find any randomised controlled trials of modest
cooling therapies after traumatic brain injury. AUTHORS' CONCLUSIONS: In order to
further explore the preliminary findings provided by animal models and
observational clinical studies that suggests there may be a beneficial effect of
modest cooling for TBI, randomised trials designed to explore the effect of these
interventions on patient-centred outcomes are needed.
PMID- 25135382
TI - Minimum 1-year results of mesh spiral-sling procedure in managing refractory and
primary disabling stress urinary incontinence.
AB - INTRODUCTION AND HYPOTHESIS: We present our minimum 1-year results with a mesh
spiral-sling procedure (MSSP) for managing refractory and disabling stress
urinary incontinence (SUI) in women. METHODS: Thirty-four women were treated with
MSSP between 2007 and 2011. Six had incomplete data and were excluded from
analysis. Study cohort comprised 21 women with refractory (mean number of
previous surgeries 2.2; range 1-6) and seen with primary disabling SUI. All
patients had marked intrinsic sphincter deficiency (ISD) with a Valsalva leak
point pressure (VLPP) <60 cm H2O. Preoperative workup included assessing the
impact of voiding symptoms using the International Consultation on Incontinence
Questionnaire--Short Form (ICIQ-SF), estimating the daily number of pads, and
urodynamic studies. Preoperative and postoperative findings were compared using
the Wilcoxon signed-rank test. RESULTS: Intraoperative unilateral bladder-neck
perforation occurred in two women during dorsal urethrolysis. With a mean follow
up of 26 months (range 12-48), SUI was cured in 71.4% of patients. Distal
urethral reconstruction with vaginal mucosal flaps was performed in two patients
with short urethral length (<2.5 cm) due to recurrence of SUI 10 months after
MSSP. Mean ICIQ-SF score decreased from 19.4 +/- 3.6 preoperatively to 7.3 +/-
2.8 postoperatively (p = 0.001). Mean daily pad number decreased from 5.2
preoperatively to 1.2 postoperatively (p = 0.02). Urethral or vaginal erosion was
not observed in any case during follow-up. CONCLUSION: Using spiral slings may be
a viable option in managing refractory and disabling SUI.
PMID- 25135383
TI - Effect of high-intensity training versus moderate training on peak oxygen uptake
and chronotropic response in heart transplant recipients: a randomized crossover
trial.
AB - In heart transplant (HTx) recipients, there has been reluctance to recommend high
intensity interval training (HIIT) due to denervation and chronotropic impairment
of the heart. We compared the effects of 12 weeks' HIIT versus continued moderate
exercise (CON) on exercise capacity and chronotropic response in stable HTx
recipients >12 months after transplantation in a randomized crossover trial. The
study was completed by 16 HTx recipients (mean age 52 years, 75% males). Baseline
peak oxygen uptake (VO2peak ) was 22.9 mL/kg/min. HIIT increased VO2peak by 4.9
+/- 2.7 mL/min/kg (17%) and CON by 2.6 +/- 2.2 mL/kg/min (10%) (significantly
higher in HIIT; p < 0.001). During HIIT, systolic blood pressure decreased
significantly (p = 0.037) with no significant change in CON (p = 0.241; between
group difference p = 0.027). Peak heart rate (HRpeak ) increased significantly by
4.3 beats per minute (p = 0.014) after HIIT with no significant change in CON (p
= 0.34; between group difference p = 0.027). Heart rate recovery (HRrecovery )
improved in both groups with a trend toward greater improvement after HIIT. The 5
month washout showed a significant loss of improvement. HIIT was well tolerated,
had a superior effect on oxygen uptake, and led to an unexpected increase in
HRpeak accompanied by a faster HRrecovery . This indicates that the benefits of
HIIT are partly a result of improved chronotropic response.
PMID- 25135385
TI - Driving Ability in Patients with Severe Chronic Low Back or Osteoarthritis Knee
Pain on Stable Treatment with Tapentadol Prolonged Release: A Multicenter, Open
label, Phase 3b Trial.
AB - INTRODUCTION: Strong centrally acting analgesics, including tapentadol prolonged
release (PR), have demonstrated efficacy for the management of non-malignant,
chronic pain. Maintaining patient independence, including the ability to drive
safely, is a key goal of long-term analgesic therapy. This multicenter, open
label, phase 3b trial evaluated the effects of tapentadol PR on driving ability.
METHODS: This study included patients who had completed previous tapentadol PR
trials for severe low back or osteoarthritis pain. After at least 6 weeks of dose
stability, patients continued taking tapentadol PR (50-250 mg twice daily) and
could take supplemental immediate-release tapentadol 50 mg, except on the day
before or day of the driving test (before the test). Pain intensity was assessed
using an 11-point numerical rating scale. The Vienna Test System-Traffic Plus was
used to assess cognitive and psychomotor function. The key surrogate parameter
for driving ability was a global judgment based on 6 battery tests. RESULTS:
Thirty-eight patients enrolled and completed the trial, and 35 patients completed
all 6 tests. Pain scores remained unchanged from enrollment to final visit [mean
(standard deviation) change, -0.2 (1.0)]. Approximately two-thirds [65.7%
(23/35)] of patients were classified as fit to drive based on the global judgment
of driving-specific ability [34.3% (12/35) not fit to drive]. Total daily
tapentadol PR dose (>200 vs. <=200 mg/day) did not affect global judgment of
driving ability (P = 0.4885). Two adverse events (considered unrelated to study
drug) were reported. CONCLUSION: Results suggest that most patients receiving a
stable dose of tapentadol PR for severe, chronic pain would be able to drive,
consistent with earlier studies evaluating stable treatment with strong opioids.
Study design limitations and needs for individual patient assessment must be
considered in clinical practice.
PMID- 25135384
TI - Oxycodone/Naloxone: role in chronic pain management, opioid-induced constipation,
and abuse deterrence.
AB - The use of opioids in the treatment of chronic pain is widespread; the prevalence
of specific opioids varies from country to country and depends on product
availability, national formulary systems, and provider preferences. Patients
often receive opioids for legitimate treatment of pain conditions, but on the
opposite side of the spectrum, nonmedical use of opioids is a significant public
health concern. Opioids are associated with several side effects, and
constipation is the most commonly reported and persistent symptom. Unlike some
adverse effects associated with opioid use, tolerance does not develop to
constipation. Opioid-induced constipation (OIC) is the most prevalent patient
complaint associated with opioid use and has been associated with declines in
various quality of life measures. OIC can be extremely difficult for patients to
tolerate and may prompt patients to decrease or discontinue opioid treatment.
Current management strategies for OIC are often insufficient. A prolonged-release
formulation of oxycodone/naloxone (OXN) has been investigated for the treatment
of nonmalignant and cancer pain and mitigation of OIC, and evidence is largely
favorable. Studies have demonstrated the capability of OXN to alleviate OIC while
maintaining pain control comparable to oxycodone-only regimens. There is
insufficient evidence for OXN efficacy for patients with mild OIC or patients
maintained on high doses of opioids, and use in these populations is
controversial. The reduction of costs associated with OIC may provide overall
cost effectiveness with OXN. Additionally, the presence of naloxone may deter
abuse/misuse by those seeking to misuse the formulation by modes of
administration other than oral ingestion. Most studies to date have occurred in
European countries, and phase 3 trials continue in the United States. This review
will include current therapeutic options for pain and constipation, unique
characteristics of OXN, evidence related to use of OXN and its place in therapy,
discussion of opioid abuse/misuse, and various abuse-deterrent mechanisms, and
areas of continuing research.
PMID- 25135386
TI - A Model-Based Meta-analysis to Compare Efficacy and Tolerability of Tramadol and
Tapentadol for the Treatment of Chronic Non-Malignant Pain.
AB - INTRODUCTION: Pain is a major symptom in many medical conditions which can be
relieved thanks to analgesics. The goal of this work was to present an indirect
comparison of efficacy and tolerability profiles of two analgesics, tramadol and
tapentadol, in patients with chronic non-malignant pain. METHODS: In the absence
of a head-to-head comparison between these two opioid drugs, model-based meta
analyses were used to characterize the pain intensity time dynamics and evaluate
the proportions of most frequent adverse events (constipation, nausea, vomiting,
dizziness, and somnolence) and drop-outs (due to adverse event, as well as due to
lack of efficacy) in each treatment group. Using these models, the
investigational treatments were compared on the basis of Monte Carlo simulation
outcomes. RESULTS: Data were extracted from 45 Phase II and Phase III studies
representing a total of 81 treatment arms, i.e., approximately 13,000 patients.
The pain intensity model shows, that after having adjusted for differences in
baseline pain intensity and placebo effects, tramadol 300 mg once daily (qd) was
slightly more effective in reducing pain than tapentadol 100-250 mg twice daily
(bid), with a 46% change from baseline for the former versus 36% for the latter.
From a tolerability standpoint, both drugs showed, as expected, increased risks
of adverse events compared to placebo. Yet, tapentadol was associated with
slightly lower risks of constipation, and nausea than tramadol. CONCLUSION:
Overall, the analysis showed that the benefit-risk profiles of tramadol 300 mg qd
and tapentadol 100-250 mg bid were approximately even. The amount of data to
characterize dose-response relationships was sufficient only in the tramadol
group; public access to tapentadol efficacy and tolerability readouts across a
wide dose range in chronic non-malignant pain would allow a comparison of
therapeutic indices, a straight quantitation of the benefit-risk ratio. Knowing
that their side-effects have been identified as potential hindrance to
prescription, a broad and open access to clinical trial data in this indication
is encouraged in order to facilitate the evaluation of the opiate analgesics
clinical utility.
PMID- 25135387
TI - Systemic ropivacaine diminishes pain sensitization processes: a randomized,
double-blinded, placebo-controlled, crossover study in healthy volunteers.
AB - INTRODUCTION: Ropivacaine is a local anesthetic widely used for regional
anesthesia. One of its advantages is low toxicity at plasma concentrations
reached systemically during continuous peripheral or central nervous block. The
objective of this study was to test the effect of systemic ropivacaine on pain,
hyperalgesia, dynamic allodynia, and flare response. METHODS: This randomized,
double-blinded, placebo-controlled, crossover study was carried out in at the
Clinical Trials Centre, University of Zurich, Switzerland. Twenty healthy male
volunteers were included in the study. Exclusion criteria were contraindications
or hypersensitivity to local anesthetics, vulnerable subjects (intellectually or
mental impaired), drug, alcohol or nicotine abuse, known peripheral neuropathies,
diabetes mellitus and/or congestive heart disease. Ropivacaine and saline were
infused intravenously during a subcutaneous electrical stimulation. The
stimulation software adjusted the stimulus strength according to the rating on a
numeric rating scale (NRS; 0-10) maintaining a NRS of 5. Areas of punctate
hyperalgesia, dynamic allodynia, and flare response were measured before and
after the infusion. RESULTS: The area of hyperalgesia increased significantly
with saline (303 +/- 380%, P < 0.05) and ropivacaine (186 +/- 137%, P < 0.05).
The area of allodynia (253 +/- 299%, P < 0.05) and flare response (112 +/- 24%, P
< 0.05) increased only during the placebo infusion. CONCLUSION: The results of
this study imply that systemic ropivacaine may diminish pain sensitization
processes.
PMID- 25135388
TI - Curcumin attenuates mechanical and thermal hyperalgesia in chronic constrictive
injury model of neuropathic pain.
AB - INTRODUCTION: The aim of this study was to observe the effect of stress caused by
neuropathic pain on serum cortisol concentration and expression of 11beta
hydroxysteroid dehydrogenase type I enzyme (11betaHSD1) in spinal cord and dorsal
root ganglions (DRG) and investigate the role and mechanism of curcumin in the
neuropathic pain of stressful rats. Neuropathic pain is a prevalent disease that
greatly impairs the patients' quality of life. A lack of the understanding of its
etiology, inadequate relief, development of tolerance and potential toxicity of
classical antinociceptives warrant the investigation of the newer agents to
relieve this pain. The aim of the present study was to explore the
antinociceptive effect of curcumin and its effect on expression of 11beta
hydroxysteroid dehydrogenase type I enzyme (11betaHSD1) in spinal dorsal horn and
DRG in chronic constriction injury (CCI) mode of neuropathic pain of rats.
METHODS: Seventy-two male Sprague-Dawley rats were randomized into four groups
with 18 rats in each: sham operation group (Sham), chronic constrictive injury
group (CCI), solvent contrast group (SC), and curcumin-treated group (Cur100).
Curcumin, 100 mg/kg/day intraperitoneal, was given for 14 days starting from the
first day after operation in the Cur100 group. Paw thermal withdrawal latency
(PTWL) and paw mechanical withdrawal threshold (PMWT) of rats were measured 2
days pre-operative, and 1, 3, 5, 7, 10, and 14 days post-operative. The animals
were deeply anesthetized and blood was taken from the heart, the lumbar segment
(L4, 5) of the spinal cord and DRG were dissected out and homogenized. The change
of cortisol was measured by enzyme-linked immunosorbent assay and the change of
11betaHSD1 expression was determined by immunochemistry and Western blot.
RESULTS: Compared with sham group, PTWL and PMWT significantly decrease after
operation in the CCI group; serum cortisol concentration was significantly
increased and the expression of 11betaHSD1 was significantly increased in the CCI
group. Comparing with CCI group, the PMWT and PTWL were increased and the serum
cortisol concentration was decreased and the expression of 11betaHSD1 was
inhibited in Cur100 group. CONCLUSION: Stress caused by neuropathic pain triggers
release of cortisol to the blood and expression of 11betaHSD1 would increase at
the same time. Curcumin could alleviate thermal and mechanical hyperalgesia
induced by CCI and inhibit the serum cortisol concentration and expression of
11betaHSD1 in the spinal cord and DRG.
PMID- 25135389
TI - Erratum to: Complex Regional Pain Syndrome Treated with Intravenous
Immunoglobulin in a Patient with Common Variable Immune Deficiency.
PMID- 25135390
TI - Molecular surveillance of the subtle septum: discovering a new mode of
peptidoglycan synthesis in streptococci.
AB - The process of septation requires precise temporal and spatial organization of
penicillin binding proteins (PBPs) and associated proteins for the deposition of
new cell wall material. In most bacteria, the filamentous protein FtsZ organises
PBPs into assemblies at the midcell which then constrict inwards as peptidoglycan
is synthesised, eventually closing the septa. Tsui et al. (2014), through the use
of fluorescent d-amino acids and high resolution microscopy, report that PBP2x of
Streptococcus pneumoniae is directed to a discrete location within the septal
aperture during the later stages of cell division. Once at this new site, PBP2x
catalyses the de novo synthesis of peptidoglycan, which is imaged by the authors
as a central 'spot', distinct from material made by other PBPs at the outer ring.
This discovery, which represents a novel mode of cell wall assembly, was made in
a directed capsular knockout of strain D39, thereby avoiding potential
mechanistic complications in commonly used laboratory strain R6. These findings
prompt not only a partial rethink of septum formation in S. pneumoniae, but
consideration of the modes of PBP localization and the subtleties that can
influence phenotypic study.
PMID- 25135391
TI - Lp-PLA2 Inhibitors for the Reduction of Cardiovascular Events.
AB - Evidence suggests that inflammation plays a central role in the pathogenesis of
atherosclerosis (Libby, Nature 420:868-874, 2002). Inflammation is a physiologic
process with highly regulated and often redundant mechanisms to balance pro
inflammatory and anti-inflammatory responses. The complexity of these networks
has made it challenging to identify those specific pathways or key enzymes that
contribute directly to atherogenesis and could act as a valuable therapeutic
target. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the
phospholipase A2 family of enzymes and is believed to contribute to
atherosclerotic plaque progression and instability by promoting inflammation. A
large number of epidemiologic studies have demonstrated that elevated levels of
Lp-PLA2 are associated with an increased risk of cardiovascular events across
diverse patient populations, independent of established risk factors including
low-density lipoprotein cholesterol. Further, a growing number of preclinical and
genetic studies support a causal role for Lp-PLA2 in atherosclerosis. The
development of a novel therapeutic agent that directly inhibits the Lp-PLA2
enzyme has provided a unique opportunity to directly test the hypothesis that
inhibition of this inflammatory enzyme will translate into improved clinical
outcomes. In this article, we will review the evidence to support the notion that
Lp-PLA2 is causally implicated in the pathobiology of atherogenesis and discuss
the potential utility of inhibiting this enzyme as a therapeutic target.
PMID- 25135393
TI - Coronary angiography utilization and costs for coronary artery bypass graft
surgery patients in Turkey.
AB - INTRODUCTION: To assess excess use of coronary angiography prior to coronary
artery bypass graft surgery and its association with mortality, health care
costs, and hospital quality in Turkey. METHODS: Using Turkish National Health
Insurance Data (2009-2011) that included patients who underwent cardiac surgery,
coronary angiography utilization was identified. Propensity score matching was
used to compare survival rates and annual health care costs of patients in a
coronary angiography excess-use group (>1 angiogram) and in a standard-therapy
group (1 angiogram). The empirical Bayesian approach was used to combine
mortality and hospital volume for quality index. The relationship between
hospital quality and excess use of coronary angiography was assessed using Chi
squared tests. RESULTS: Out of 20,126 patients identified, 7.27% of patients
underwent excessive coronary angiography procedures (excess-use group), with an
average annual cost at 9.7% higher than those who had a single angiography
(standard-therapy group; P < 0.01). Operational mortality associated with
excessive use was significantly higher as well (7.4% versus 5.4%, P < 0.02).
There exists variation in the use of coronary angiography across cities and
hospitals. Patients who underwent cardiac surgery in high-quality hospitals were
less likely to have excessive angiography use than those in low-quality hospitals
(7.0% versus 9.5%, P < 0.01). CONCLUSION: In Turkey, excess use of coronary
angiography prior to coronary artery bypass graft surgery is associated with
higher operational mortality, higher expenditures, and lower hospital quality.
PMID- 25135392
TI - Anticoagulation in Patients Aged >=75 years with Atrial Fibrillation: Role of
Novel Oral Anticoagulants.
AB - Atrial fibrillation (AF) is an important cause of preventable, disabling stroke
and is increasingly prevalent with advancing age. As life expectancies increase
around the world, AF-related stroke is a growing global public health concern.
Most AF patients are elderly (>=75 years old) and increasing age is a consistent
independent risk factor for AF-associated stroke. Warfarin anticoagulation is
highly effective for stroke prevention in AF patients, but is underutilized
especially in the elderly. Although elderly patients are at increased risk of
hemorrhage with oral anticoagulants, the benefit for ischemic stroke reduction
exceeds the risk of hemorrhage for most elderly patients. Consequently, age alone
should not be considered a contraindication for anticoagulation. Novel oral
anticoagulants such as dabigatran, rivaroxaban and apixaban are at least as
effective as warfarin in preventing strokes in patients with AF. Relative to
warfarin, these novel agents reduce the risk of intracranial hemorrhage, the most
devastating complication of anticoagulation therapy in elderly AF patients. The
novel oral anticoagulants are especially appealing for stroke prevention in
elderly patients with AF.
PMID- 25135394
TI - Medical Costs of Oral Anticoagulants vs Warfarin for Atrial Fibrillation Patients
with Different Stroke Risks.
AB - INTRODUCTION: The Apixaban for the Reduction in Stroke and Other Thromboembolic
Events in Atrial Fibrillation (ARISTOTLE), Randomized Evaluation of Long-term
Anticoagulation Therapy (RE-LY), and Rivaroxaban Once Daily Oral Direct Factor Xa
Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and
Embolism Trial in Atrial Fibrillation (ROCKET-AF) trials demonstrated that the
oral anticoagulants (OACs), apixaban, dabigatran, and rivaroxaban, respectively,
are efficacious for stroke prevention among nonvalvular atrial fibrillation
(NVAF) patients. Based on clinical trial results this study evaluated medical
costs of clinical events associated with use of individual OACs relative to those
of warfarin in NVAF patients with moderate and high stroke risk. METHODS: Rates
for primary and secondary efficacy and safety outcomes (i.e., clinical events)
among NVAF patients with CHADS2 = 2 and >=3 were determined from the three OAC
trials. One-year incremental costs among patients with clinical events from a US
payer perspective were obtained from the literature and inflation adjusted to
2010 costs. Medical costs for clinical events associated with each OAC vs.
warfarin were estimated and compared. RESULTS: For NVAF patients with moderate
stroke risk (CHADS2 = 2) differences in clinical event medical costs vs. warfarin
were -$298, -$143, and +$117 per patient year for apixaban, dabigatran (150 mg),
and rivaroxaban, respectively (negative numbers indicate cost reduction). For
NVAF patients with high stroke risk (CHADS2 >= 3) differences in clinical event
medical costs vs. warfarin were -$697, +$2, and -$100 for apixaban, dabigatran
(150 mg), and rivaroxaban, respectively. CONCLUSIONS: Medical cost differences
associated with OACs vs. warfarin vary according to stroke risk. Of the three
OACs, apixaban demonstrated consistent medical cost reductions vs. warfarin for
NVAF patients with moderate and high stroke risks.
PMID- 25135395
TI - StentBoost Visualization for the Evaluation of Coronary Stent Expansion During
Percutaneous Coronary Interventions.
AB - INTRODUCTION: Inadequate stent implantation is associated with stent thrombosis
and restenosis. StentBoost can enhance stent visualization and evaluate stent
expansion. Currently, there are limited comparison studies between StentBoost and
intravascular ultrasound (IVUS). We aimed to test the correlation and agreement
between IVUS and StentBoost measurements. METHODS: From December 2010 to December
2011, 38 patients (54 stents) were analyzed using IVUS and StentBoost. Minimal
stent diameter and proximal and distal edge stent diameter were compared between
imaging techniques using Pearson correlation and Bland-Altman scatter plot.
RESULTS: There was good correlation between StentBoost and IVUS measurements
regarding minimal stent diameter (p < 0.001 in all stent portions) and an optimal
agreement between IVUS and StentBoost, while lesser agreement was found between
IVUS and quantitative coronary angiography. CONCLUSION: The assessment of stent
implantation using StentBoost showed an adequate correlation and agreement with
IVUS. This easily applicable angiographic technique can be used to guide stent
implantation.
PMID- 25135396
TI - Cardiac sarcoidosis: case report, workup, and review of the literature.
AB - INTRODUCTION: Cardiovascular disease is the leading cause of death worldwide,
with coronary heart disease being the most common manifestation disease. While
deaths attributed to coronary heart disease are falling in the developed world,
the number of patients with cardiomyopathy continues to increase. In this paper,
the current literature on imaging modalities for infiltrative and inflammatory
cardiomyopathies is reviewed, focusing on the three most common diagnoses, namely
sarcoidosis, amyloidosis, and myocarditis. CASE REPORT: A 43-year-old male
presented with palpitations and left ventricular systolic dysfunction for a
second opinion following an initial nondiagnostic workup. The employed clinical
and radiologic approach that led to a definitive diagnosis and disease-specific
treatment is presented here. CONCLUSION: The current algorithms and the strengths
and weaknesses of the various radiologic techniques in establishing a diagnosis
in patients who present with new onset cardiomyopathy are reviewed.
Recommendations are provided regarding the selection between echocardiography,
computed tomography radionuclide imaging, and magnetic resonance imaging in
diagnosing the various causes of cardiomyopathy.
PMID- 25135397
TI - Acute dissection of the descending aorta: a case report and review of the
literature.
AB - Cardiovascular disease is the leading cause of death worldwide. Acute aortic
syndromes, which include aortic dissection, intramural hematoma, and penetrating
aortic ulcer, represent the most morbid presentations of aortic disease and can
be difficult to diagnose. Recent advances in imaging have allowed for more rapid
and accurate diagnosis of acute aortic syndromes and the options for management
are expanding. This case report and review presents the case of a 43-year-old man
with acute type B aortic dissection who underwent two endovascular procedures for
malperfusion syndrome. The review focuses on the presentation, diagnosis, medical
management, and procedural options for acute dissection of the descending aorta.
PMID- 25135398
TI - The medial sural artery perforator flap and its application in electrical injury
to the hand.
AB - We describe the use of a free medial sural artery perforator flap to reconstruct
a complex composite defect to the dorsum of the right index finger following a
low voltage electrical injury. The resulting defect was a 3.5 * 5 cm full
thickness wound, with segmental tendon loss and loss of underlying periosteum.
Due to both size and local vascular injury related to the mechanism, free tissue
transfer was felt to be the most reliable option to resurface the composite
defect in a single stage. The medial sural artery perforator flap, for reasons
outlined below, was felt to be the best option: 1. Thin profile. 2. Vascularised
fascia can be taken as a tongue, adjacent to the skin paddle: a gliding surface
to prevent the tendon graft sticking to exposed bone. 3. Long pedicle: micro
anastomosis away from zone of injury. 4. Little donor site morbidity: can be
closed directly (if <6 cm wide) and does not require sacrifice of any major blood
vessel. 5. Can be harvested with nerve and tendon from the same wound. 6. Can
include as little or as much tissue required and compared to other
fasciocutaneous flaps matches the texture and thickness of the hand most closely.
We describe the reconstruction of the composite defect on day 42 post-injury,
following one prior debridement. This case highlights the versatility and
suitability of the medial sural artery flap in the reconstruction of complex hand
burns with resulting composite defects.
PMID- 25135399
TI - Validation of diagnosis of aplastic anaemia in La Rioja (Spain) by International
Classification of Diseases codes for case ascertainment for the Spanish National
Rare Diseases Registry.
AB - OBJECTIVE: To analyse the validity of diagnosis of aplastic anaemia (AA) by
International Classification of Diseases codes in hospital discharge data (MBDS)
and the mortality registry (MR) of La Rioja to detect cases to be included in the
Spanish National Rare Diseases Registry. METHODS: International Classification of
Diseases (ICD) codes were used to detect AA cases during the period 2007-2012
from two administrative databases: the MBDS and the MR of La Rioja (Spain).
Medical records of population selected by merging both databases were used to
confirm true AA cases. The annual mean incidence rate of AA was calculated using
confirmed incident cases. RESULTS: By merging both databases, 62 hypothetical AA
incident patients were detected during the period 2007-2012. The medical records
of the 89% of them could be revised, and they confirmed that only the 15% of the
patients actually suffered AA. The annual mean AA incidence in La Rioja was 4.17
per million inhabitants (6.23 per million, males; 2.10 per million, females).
CONCLUSIONS: The MBDS and the MR are not in themselves sufficient to ascertain AA
cases in La Rioja and medical records should be reviewed to confirm true AA cases
to be included in the Spanish National Rare Diseases Registry.
PMID- 25135403
TI - [Early rehabilitation program in uncomplicated Stanford type B acute aortic
dissection].
AB - Between December 2009 and August 2011, 120 patients with uncomplicated Stanford
type B acute aortic dissection( UBAD) received medical treatment. In October
2010, we initiated an early rehabilitation program for UBAD patients in an acute
phase. This early rehabilitation program, which was aimed at enabling the patient
to walk around the ward within 2 days, was conducted for 87 consecutive
patients;the remaining 33 were subjected to the conventional rehabilitation
program. Mortality was not significantly different between the 2 groups. The
incidence of atelectasis, need for mechanical ventilation, and intensive care
unit syndrome during medical treatment occurred in 48% (16/33), 15% ( 5/33), and
30% ( 10/33), respectively, of the conventional group and in 3.4% ( 3/87), 1.1%
(1/87), and 3.4% ( 3/87), respectively, of the early rehabilitation group. The
outer diameter of the aorta was dilated after 4 weeks' rehabilitation in smaller
percentage of patients in the early rehabilitation group than the conventional
one. Thus, the early rehabilitation program was more effective for patients with
UBAD than the conventional one.
PMID- 25135404
TI - [Computed tomography (CT) assessment of the postoperative change of pericardial
fat pad used in pulmonary surgery].
AB - The purpose of this study is to clarify the postoperative change of pericardial
fat pad used in pulmonary resection to reinforce bronchial suture or bronchial
stump. 5 cases who received chest computed tomography (CT) examination 2 times or
more after the operation (once within one week after the operation) were
enrolled. For evaluation, scoring system from 1 to 4 according to the percentage
of remaining pericardial fat pad was applied(1 point: 0~19%, 2 point: 20~49%, 3
point: 50~79%, 4 point: 80~100%). At 1 to 2 months after the operation, almost
all cases were 3 or 4 point. However, the scores declined to 1 or 2 point 5
months after the operation in almost all cases. It is likely that the pericardial
fat pad remains to be effective in protecting bronchial stump or anastomosis 1 to
2 months after the operation.
PMID- 25135405
TI - [Predictors of chronic aortic events associated with uncomplicated type B aortic
dissection].
AB - OBJECTIVE: Stent-graft repair may emerge as a first-line therapy for acute
complicated type B dissection(C-TBD), while debate continues over thoracic
endovascular aortic repair (TEVAR) for uncomplicated type B aortic dissection (U
TBD). Aggressive medical therapy, which confers a 1-year survival rate of 80-90%,
is deemed appropriate for most of these patients. However, it is reported that
aortic complications occur in <= 50% patients within 5 years after surgery.
Subgroups of patients with U-TBD may benefit from early stent-graft placement,
but identification of these patients remains difficult. Therefore, we assessed
the predictors of chronic aortic events associated with U-TBD. METHODS: Between
January 2001 and April 2012, 49 patients diagnosed with communicating U-TBD
without aneurysm formation were admitted to our hospital. These patients were
divided into 2 groups:group AC (n=25) with chronic aortic complications (aneurysm
formation, aortic diameter expansion of 5 mm/0.5 year, re-dissection, and
rupture) and group NC (n=24)with no aortic complications. We assessed and
compared patient profiles and imaging findings between the 2 groups. RESULTS:
Aortic diameter >= 40 mm was more often seen in group AC than in group NC
(p=0.018). In addition, intimal tear in the distal arch was more often seen in
group AC than in group NC ( p=0.002). Initial aortic diameter was significantly
larger in group AC than in group NC (p=0.004). There was no significant
difference in the length of communicating false lumen between the 2 groups (
p=0.107). CONCLUSIONS: Early endovascular intervention may be appropriate for U
TBD in cases displaying an initial aortic diameter >= 40 mm and an initial tear
in the distal arch. It is expected that randomized studies, including ADSOAB
study (a study on the efficacy of endovascular grafting in uncomplicated acute
dissection of the descending aorta.), will resolve the limitations of our
retrospective study.
PMID- 25135400
TI - P2X4 receptor regulates alcohol-induced responses in microglia.
AB - Mounting evidence indicates that alcohol-induced neuropathology may result from
multicellular responses in which microglia cells play a prominent role.
Purinergic receptor signaling plays a key role in regulating microglial function
and, more importantly, mediates alcohol-induced effects. Our findings demonstrate
that alcohol increases expression of P2X4 receptor (P2X4R), which alters the
function of microglia, including calcium mobilization, migration and
phagocytosis. Our results show a significant up-regulation of P2X4 gene
expression as analyzed by real-time qPCR (***p < 0.002) and protein expression as
analyzed by flow cytometry (**p < 0.004) in embryonic stem cell-derived
microglial cells (ESdM) after 48 hours of alcohol treatment, as compared to
untreated controls. Calcium mobilization in ethanol treated ESdM cells was found
to be P2X4R dependent using 5-BDBD, a P2X4R selective antagonist. Alcohol
decreased migration of microglia towards fractalkine (CX3CL1) by 75 % following
48 h of treatment compared to control (***p < 0.001). CX3CL1-dependent migration
was confirmed to be P2X4 receptor-dependent using the antagonist 5-BDBD, which
reversed the effects as compared to alcohol alone (***p < 0.001). Similarly, 48 h
of alcohol treatment significantly decreased phagocytosis of microglia by 15 %
compared to control (*p < 0.05). 5-BDBD pre-treatment prior to alcohol treatment
significantly increased microglial phagocytosis (***p < 0.001). Blocking P2X4R
signaling with 5-BDBD decreased the level of calcium mobilization compared to
ethanol treatment alone. These findings demonstrate that P2X4 receptor may play a
role in modulating microglial function in the context of alcohol abuse.
PMID- 25135406
TI - [Aortoplasty with autologous pulmonary patch for the ascending aortic stenosis
after interrupted aortic arch repair].
AB - We experienced a case of ascending aortic stenosis after interrupted aortic arch
repair. At the first operation in the neonatal period, diameter of the aortic
annulus was 4.8 mm and no subvalvular stenosis was presented. Aortic arch was
reconstructed with conventional technique of extended end-to-end anastomosis.
Although ascending aortic stenosis was observed at the time, that had not been
severe, however, the stenosis was exacerbated with time. At the catheterization 9
months after the operation, pressure gradient between aortic root and descending
aorta was 72 mmHg. Therefore reoperation was carried out. Ascending aortoplasty
using aoutologous pulmonary patch was performed. Pulmonary artery was repaired
with aotologous pericardial patch. Despite mild pulmonary stenosis was observed,
the postoperative course was favorable.
PMID- 25135407
TI - [Maze procedure in a case of dextrocardia with atrial septal defect and
persistent left superior vena cava].
AB - A 52-year-old man was diagnosed with dextrocardia at the age of 1 year and was
asymptomatic until 1 year before admission. He was transferred to our hospital
for management of atrial fibrillation. A transthoracic echocardiogram showed
dextrocardia with atrial septal defect;moderate tricuspid valve regurgitation;
and a large, persistent left superior vena cava. A cardiac catheterization study
revealed that pulmonary flow/systemic flow (Qp/Qs) was 3.6 and that pulmonary
vascular resistance was 2.5 Wood U.m2. Intracardiac repair with tricuspid
annuloplasty and a maze procedure was scheduled. When establishing
cardiopulmonary bypass, venous drainage was initially obtained from the inferior
vena cava and the left superior vena cava, and the small superior vena cava was
then directly cannulated after opening the right atrium. The patient's
postoperative course was uneventful, and serial electrocardiograms have
demonstrated maintenance of normal sinus rhythm for 3.5 years after the
operation.
PMID- 25135408
TI - [Coronary artery bypass grafting in a patient with chronic bird fancier's lung].
AB - Acute exacerbation is a devastating and fatal event of hypersensitivity
pneumonitis. We report an 80-year-old man with chronic bird fancier's lung which
acutely exacerbated after off-pump coronary artery bypass grafting. Our
perioperative management included avoidance of inhalation of high concentration
oxygen, administration of neutrophil elastase inhibitor, and long-term
administration of antibiotics. Nevertheless, the patient experienced severe
respiratory failure after influenza infection. High-resolution computed
tomography (CT) showed new ground-glass opacities overlying fibrosis and traction
bronchiectasis. We diagnosed acute exacerbation of hypersensitivity pneumonitis.
Immediate steroid pulse therapy with empirical antibiotic administration was
effective, and he recovered from critical respiratory failure. High-resolution CT
was very helpful in the early detection of acute exacerbation of pneumonitis.
PMID- 25135409
TI - [Surgical treatment of innominate artery aneurysm using temporary bypass to
prevent cerebral ischemia].
AB - A 69-year-old woman had an innominate artery aneurysm that was adjacent to the
right common carotid artery and the right subclavian artery. The patient had a
dominant right vertebral artery and an underdeveloped circle of Willis. At
surgery, the proximal site of the innominate artery, the right common carotid
artery and the right subclavian artery were clamped with the temporary bypass
between the ascending aorta and the distal site of the right brachial artery for
maintaining the blood flow to the brain. The innominate artery aneurysm was
resected, and a woven Dacron Y-shaped graft, 14*7 mm in diameter, was used for
reconstructing the innominate artery, the right subclavian artery and the right
common carotid artery. The postoperative course was uneventful and there was no
postoperative neurological deficit. Temporary bypass for maintaining cerebral
perfusion was useful in preventing cerebral ischemia.
PMID- 25135410
TI - [Quadricuspid aortic valve; report of two cases].
AB - Quardicupid aortic valve( QAV) is a comparatively rare congenital anomaly, which
presents with frequent aortic regurgitaion ( AR) due to sclerotic changes. We
report 2 cases (a 67-year-old woman and a 53-year-old man) of QAV associated with
AR. We made an definite diagnosis by preoperative transthoracic and
intraoperative transesophageal echocardiography. Intraoperative findings showed
type C QAV in case 1 and type B QAV in case 2 according to the Hurwitz
classification. The left coronary ostia was slightly shifted to the aortic root
in case 1. There were no other congenital anomalies, therefore only aortic valve
replacement with mechanical prosthesis was performed in both cases. The
postoperative courses were uneventful.
PMID- 25135411
TI - [Right ventricular rupture due to blunt trauma diagnosed by MDCT; report of a
case].
AB - The survival rate of cardiac rupture due to blunt trauma is generally low. We
experienced a case with right ventricular rupture due to blunt trauma. The
patient was a 49-year-old man who was crushed in a traffic accident and
transported to a local hospital in a shock state. He was diagnosed with cardiac
tamponade due to cardiac rupture, and for pericardial drainage was immediately
performed. He was then transferred to our hospital for emergency surgery. His
hemodynamics was stable, and he was diagnosed with right ventricular rupture by
multi-detector row computed tomography (MDCT). The operation was performed
successfully without cardiopulmonary bypass, and his postoperative course was
uneventful. MDCT is useful for detecting the rupture site of the heart.
PMID- 25135412
TI - [Thoracic endovascular aneurysm repair combined with debranching and chimney
methods in a high risk patient; report of a case].
AB - We report a case of a 77-year-old man with a thoracic aortic aneurysm, combined
with chronic myelomonocytic leukemia, polymyalgia rheumatica, and atial
fibrillation. Open surgery was considered as high risk because he was severely
ill. Instead, partial debranching and stent graft( TEVAR) were performed by
chimney method. He had no major complication after surgery, and was discharged on
foot on the 15th postoperative day. In high risk cases of thoracic aortic
aneurysm, TEVAR with debranching and chimney methods is effective.
PMID- 25135413
TI - [Endovascular stent-grafting for rupture of descending aorta with a patient with
severe arterial occlusive disease; report of a case].
AB - A patient was a 63-year-old woman with poor cardiac function and systemic
arterial occlusive disease, who complained of severe back pain. Computed
tomography (CT) revealed a rupture of the descending aorta. Initially, abdominal
aortic approach through open laparotomy was attempted, but a guide wire caused
local aortic dissection. Then, after median sternotomy, endovascular stent was
successfully deployed through the ascending aorta. Postoperative course was
uneventful. Follow-up CT showed no endoleak. A less invasive endovascular repair
would be an alternative treatment for high risk patients such as this case, but
several access routes should be considered, especially in a patient with systemic
arterial occlusive disease.
PMID- 25135414
TI - [Mid-aortic syndrome in 2-year old boy presenting with severe left ventricular
dysfunction; report of a case].
AB - Mid aortic syndrome is uncommon acquired or congenital condition characterized by
segmental narrowing of the abdominal or distal descending thoracic aorta. If left
untreated, it result in life threatening complications. We described the case of
2-year-old boy admitted to our hospital for hypertension and heart failure.
Diagnosis of mid aortic syndrome was made with severe stenosis in distal
descending aorta. With consideration of growth, we avoided bypass grafting and
implantation with prothesic graft. For severe adhesion, we performed patch
aortoplasty with 0.4 mm expanded polytetrafluoroethylene (ePTFE) patch.
Postoperative course was unevetful. His blood pressure and left ventricular
function was normalized. He was discharged on the 20st day after the surgery.
PMID- 25135415
TI - [Aortic valve replacement in a patient with antiphospholipid syndrome; report of
a case].
AB - A 76-year-old woman with primary antiphospholipid syndrome (APS) was referred to
our hospital due to severe aortic valve stenosis. We performed aortic valve
replacement using a bioprosthetic valve. Her postoperative course was uneventful.
She was discharged in good health on postoperative day 33. As for cardiovascular
operations in APS patients, high rates have been reported of perioperative
mortality and thromboembolic and bleeding events. Perioperative management of
anticoagulation must be strict.
PMID- 25135416
TI - [Mitral valve replacement after previous coronary artery bypass grafting with
functioning left internal thoracic artery graft: effectiveness of the method
using a direct vision retrosternal approach; report of a case].
AB - Performing a redo-sternotomy when a mammary artery graft is patent can be rather
difficult. We previously reported a redo-sternotomy technique involving direct
visualization with a retrosternal dissection (DR) method using a Kent's
retractor. The DR method in detail is as follows: 1) A midline skin incision is
extended to the abdomen about 5 cm. 2) The bilateral costal arches are divided
from the rectal muscle. 3). A pair of retractors is placed under the costal arch.
4) A stainless steel wire is applied to the previous sternal wire at the center
of the sternum. 5) The retractor and sternal wire are lifted up using the Kent's
retractor to widen the retrosternal space. 6) The sternum and sub-sternal tissue
are carefully divided using an electronic scalpel or metal retractor with an
entirely sternal length. 7) Routine sternotomy is performed using a Stryker.
Herein, we report a patient who had undergone cardiac surgery, coronary artery
bypass grafting (CABG), using a left internal mammary artery and mitral
annuloplasty 2 years previously, and then developed mitral regurgitation caused
by infectious endocarditis. He successfully underwent redo-sternotomy and mitral
valve replacement using the DR method. In a patient with a patent internal
mammary artery, the DR method greatly reduces the risk of graft injury.
PMID- 25135417
TI - [Acute abdominal aortic occlusion in a patient with a giant thrombus in the left
atrium and mitral stenosis; report of a case].
AB - The patient was a 69-year-old male who had had percutaneous transvenous mitral
commissurotomy (PTMC) 15 years ago, and had stopped taking warfarin after PTMC.
He was transferred to our emergency room( ER) because of sudden severe pain in
his both lower legs. We recognized pulselessness in his both femoral arteries,
and pallor, paresthesia and poikilothermia in his lower extremities.
Electorocardiogram(ECG) showed arterial fibrillation, and computed tomography(
CT) showed occlusion of the abdominal aorta just below inferior mesenteric
artery( IMA) and both common iliac arteries. By echocardiography, a giant
thrombus was detected in the left atrium with severe mitral stenosis.
Thrombectomy and angioplasty were performed at about 5 hours after the onset of
occlusion, and revascularization was successful. Three days after the operation,
we excised the giant thrombus in the left atrium and performed mitral valve
replacement because we considered that myonephropathic metabolic syndrome (MNMS)
had been prevented. The postoperative course was uneventful and he was discharged
on the 27th postoperative day.
PMID- 25135418
TI - [Bilateral congenital coronary-pulmonary artery fistulas; report of a case].
AB - Bilateral coronary-pulmonary artery fistulas are very rare. We report a case of a
68-year-old woman without any previous medical history, who presented to our
hospital after slow onset of chest heaviness on exertion. Coronary computed
tomography (CT) and angiography revealed 2 fistulas:one arising from the left
anterior descending artery accompanied by an aneurysm and the other from the
right coronary artery. We opened the trunk of the pulmonary artery under cardio
pulmonary bypass and cardiac arrest. We recognized the outflow of the shunt just
above the right pulmonary cusp, which was closed from the outside. We also closed
the aneurysm of the shunt. Neither the fistulas nor the aneurysm was recognized
by postoperative CT. The chest symptom disappeared.
PMID- 25135419
TI - [Small intestinal perforation due to metastasis from pulmonary pleomorphic
carcinoma; report of a case].
AB - A 63-year-old male patient was referred to our department for an abnormal shadow
in the left middle lung field. The patient underwent trans bronchial lung biopsy
and pathological finding was adenocarcinoma. Computed tomography( CT) showed mass
in the left lower lobe, nodules in the bilateral adrenal glands, liver, pancreas
and lumbar bone. When he was admitted to our hospital for chemotherapy, chest X
ray showed left pneumothorax and a chest tube was placed. Several days later, he
complained of sudden abdominal pain and abdominal CT revealed free air around
small intestine. Emergency operation was done and the perforation of the small
intestine due to metastasis was found. He underwent partial resection of small
intestine and left lower lobectomy. Pathological diagnosis was pulmonary
pleomorphic carcinoma and small intestine metastasis.
PMID- 25135420
TI - [Descending necrotizing mediastinitis resulting from acute epiglottitis; report
of a case].
AB - Descending necrotizing mediastinitis (DNM) is a serious condition due to abscess
spreading from neck into mediastinum. We report a case of DNM following acute
epiglottitis and abscess. A 59-year old male visited our hospital for parotid
swelling, pyrexia, and dyspnea, and was diagnosed as having acute epiglottitis at
otology and hospitalized. Despite right tonsillectomy, drainage and tracheostomy
on day 6 after hospitalization, he developed DNM and was referred to our
department. Drainage of mediastinal regions( anterior to the trachea and tracheal
bifurcation, inferoposterior mediastinum and posterior to the left main bronchus)
was performed on day 14 after hospitalization. Postoperative course was
uneventful.
PMID- 25135421
TI - Discrete trinuclear copper(II) compounds as building blocks: the influence of the
peripheral substituents on the magnetic coupling in oxamato-bridged complexes.
AB - Two new trinuclear copper(ii) complexes without end-capping ligands,
(Bu4N)2[Cu(dmso)2{Cu(dnopba)(dmso)}2] () and
(Bu4N)2[Cu(dmso)2{Cu(dcopba)(dmso)}2] () [dnopba = 4,5-dinitro-ortho
phenylenebis(oxamate), dcopba = 4,5-dichloro-ortho-phenylenebis(oxamate), Bu4N(+)
= tetra-n-butylammonium and dmso = dimethylsulfoxide], were synthesized and their
structures were determined by single crystal X-ray diffraction. The crystal
structures of and consist of two outer bis(oxamato)(dmso)cuprate(ii) units which
act as bidentate ligands toward a trans-bis(dmso)copper(ii) inner entity leading
to centrosymmetric tricopper(ii) complexes with copper-copper separations across
the oxamate bridges of 5.1916(3) () and 5.1776(3) A (). The peripheral copper(ii)
ions in and are five-coordinate in somewhat distorted square pyramidal
environments with a dmso molecule filling the apical position whereas the inner
copper(ii) ion is six-coordinate in an elongated octahedral environment with two
dmso molecules in the axial sites. The investigation of their magnetic properties
in the temperature range 2.0-300 K shows the occurrence of a strong
intramolecular antiferromagnetic coupling between the copper(ii) ions through the
oxamate bridges [J1 = -296(1) () and -334(1) cm(-1) (), the Hamiltonian being
defined as H = -J1(SCu2.SCu1 + SCu2.SCu1')], which leads to a low-lying spin
doublet at low temperatures. Density functional theory calculations (DFT) have
been used to substantiate these magnetic couplings and also to analyse the
influence exerted on these interactions by the type of substituent at the 4,5
positions from the phenylene ring of the bis(oxamate) ligand.
PMID- 25135422
TI - Ecotoxicological and genotoxic assessment of hospital laundry wastewaters.
AB - The aim of the present study was to assess the ecotoxicity and genotoxicity of
hospital laundry wastewaters generated from a regional hospital located in Rio
Pardo Valley in the state of Rio Grande do Sul, Brazil. Physicochemical,
microbiological, ecotoxicological, and genotoxic analyses were performed, and the
results indicate that some parameters were not in accordance with the limit
concentrations established by Brazilian and international guidelines for urban
wastewaters. Daphnia magna (EC50 2.01%) and Danio rerio (LC50 29.25%) acute
toxicity was detected, and sublethal effects were identified in Lactuca sativa
(IC25 12.50%) and Allium cepa (IC25 51.25%). Cytotoxicity was observed at the
five wastewater concentrations used yielding statistically significant
differences (p < 0.05) in the meristematic cells of A. cepa compared with the
negative control. The results obtained here warn about the necessity to develop
treatment methods that can mitigate the environmental impacts caused by the
ecotoxicity and genotoxicity of hospital laundry wastewaters.
PMID- 25135424
TI - Variable phenotypes of sickle cell disease in India with the Arab-Indian
haplotype.
PMID- 25135423
TI - Combining diffusion and perfusion differentiates tumor from bevacizumab-related
imaging abnormality (bria).
AB - A subset of patients with high-grade glioma and brain metastases who are treated
with bevacizumab develop regions of marked and persistent restricted diffusion
that do not reflect recurrent tumor. Here, we quantify the degree of restricted
diffusion and the relative cerebral blood volume (rCBV) within these regions of
bevacizumab-related imaging abnormality (BRIA) in order to facilitate
differentiation of these lesions from recurrent tumor. Six patients with high
grade glioma and two patients with brain metastases who developed regions of
restricted diffusion after initiation of bevacizumab were included. Six pre
treatment GBM controls were also included. Restriction spectrum imaging (RSI) was
used to create diffusion maps which were co-registered with rCBV maps. Within
regions of restricted diffusion, mean RSI values and mean rCBV values were
calculated for patients with BRIA and for the GBM controls. These values were
also calculated for normal-appearing white matter (NAWM). RSI values in regions
of restricted diffusion were higher for both BRIA and tumor when compared to
NAWM; furthermore RSI values in BRIA were slightly higher than in tumor.
Conversely, rCBV values were very low in BRIA-lower than both tumor and NAWM.
However, there was only a trend for rCBV values to be higher in tumor than in
NAWM. When evaluating areas of restricted diffusion in patients with high-grade
glioma or brain metastases treated with bevacizumab, RSI is better able to detect
the presence of pathology whereas rCBV is better able to differentiate BRIA from
tumor. Thus, combining these tools may help to differentiate necrotic tissue
related to bevacizumab treatment from recurrent tumor.
PMID- 25135425
TI - Self-assembly: an option to nanoporous metal nanocrystals.
AB - Nanoporous metal nanocrystals involving both nanoscale effects and nanopore
properties hold enormous promising potential for various important applications
due to their unique structures such as large surface area per unit volume and
interconnected open framework. Self-assembly, as an excellent option, has been
developed to control the desired structure and rational performance of nanoporous
metal nanocrystals. After identifying features of their methodologies and
structures, the control of synthesis based on the self-assembly technique is
thoroughly discussed. The development of the self-assembly synthesis methodology
is then presented in detail. The emerging application, mainly in catalysis, and
corresponding design are finally summarized.
PMID- 25135426
TI - Identification of microRNAs as novel biomarkers for detecting esophageal squamous
cell carcinoma in Asians: a meta-analysis.
AB - Accumulating evidence has suggested that microRNAs (miRNAs) may play potential
role as ideal diagnostic indicators of esophageal squamous cell carcinoma (ESCC).
However, previous studies have met discrepant results. Thus, we conducted this
meta-analysis to assess the potential diagnostic value of miRNAs for ESCC. A
systematic literature search was conducted in PubMed and other databases. The
pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR),
negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the
curve (AUC) were calculated to evaluate the overall test performance. The Q
statistic and the I(2) test were used to assess between-study heterogeneity. The
potential sources of heterogeneity were further analyzed by subgroup analyses and
meta-regression. Seventeen studies from eight articles, including 995 ESCC
patients and 733 healthy controls, were included in this meta-analysis. The
pooled SEN and SPE were 0.81 (95% confidence interval (CI) 0.76-0.85) and 0.83
(95 % CI 0.76-0.88), respectively. The pooled PLR was 4.6 (95% CI 3.3-6.5), NLR
was 0.23 (95% CI 0.19-0.29), and DOR was 20 (95% CI 13-31). The pooled AUC was
0.91 (95% CI 0.88-0.93). Subgroup analyses indicated that blood-based miRNA assay
displays better diagnostic accuracy than saliva-based miRNA assay. In summary,
miRNA analysis may serve as novel noninvasive biomarkers for ESCC with excellent
diagnostic characteristic. In addition, subgroup analysis suggested that blood
based assay yields better diagnostic characteristics than saliva-based assay.
However, many issues should be managed before these findings can be translated
into a clinically useful detection method for ESCC.
PMID- 25135427
TI - Reproductive factors in relation to risk of brain tumors in women: an updated
meta-analysis of 27 independent studies.
AB - Previous studies on the association between reproductive factors and brain tumor
risk in women have provided inconclusive findings. Thus, an updated meta-analysis
was performed to obtain more precise risk estimates for brain tumor regarding
several common reproductive factors. A comprehensive literature search for
relevant publications in the PubMed and Embase databases was carried out from
their inception up to June 20, 2014. Pooled relative risks (RRs) with
corresponding 95% confidence intervals (CIs) were calculated. There were 27
independent studies with a total of 12,129 cases and 1,433,915 controls included
into the present meta-analysis. We found that an elevated risk of brain tumors
(RR=1.17, 95% CI 1.06-1.29, P=0.002), particularly glioma (RR=1.33, 95% CI 1.15
1.54, P<0.001), was related to older age at menarche. Interestingly, stratified
analysis by type of brain tumors showed that the longer duration of breast
feeding was associated with the risk of meningioma negatively but glioma
positively (for meningioma: RR=0.76, 95% CI 0.64-0.91, P=0.002; for glioma:
RR=1.70, 95% CI 1.14-2.55, P=0.010). No significant association was observed when
estimating the roles of other reproductive factors including parity, age at first
birth, menopausal status, and age at menopause in brain tumorigenesis. Our study
suggests that older age at menarche is a risk factor of brain tumors and glioma
in particular. Additionally, more studies are warranted to further elucidate
roles and mechanisms of common reproductive factors in the risk of brain tumors.
PMID- 25135429
TI - Molecular regulation of cervical cancer growth and invasion by VEGFa.
AB - Although antivascular endothelial growth factor a (VEGFa) treatment has been well
applied in cervical cancer therapy, the underlying molecular basis has not been
precisely identified. Here, we examined the levels of VEGFa on the tumor growth
and invasion in four commonly used human cervical cancer cell lines. We found
that overexpression of VEGFa in these lines increased the tumor growth and
invasiveness, while inhibition of VEGFa decreased the tumor growth and
invasiveness. To figure out the involved signaling pathways, we applied specific
inhibitors for ERK/MAPK, JNK, and PI3K/Akt signaling pathways, respectively, to
VEGFa-overexpressing cervical cancer lines and found that only inhibition of
PI3K/Akt signal transduction abolished VEGFa-induced increases in cell growth and
invasiveness. Inhibition of Akt downstream mTor signaling similarly inhibited
cell growth and invasion in VEGFa-overexpressing cervical cancer cells,
suggesting that VEGFa may activate PI3K/Akt, and subsequently its downstream mTor
signaling pathway, to promote cervical cancer cell growth and invasion.
Furthermore, the effects of VEGFa-induced activation of mTor signaling cascades
appeared to promote cancer cell growth through cyclinD1 and CDK4 activation and
promote cancer cell invasion through MMP2 and MMP3. Taken together, our data
suggest that anti-VEGFa treatment in cervical cancer may inhibit both tumor cell
growth and invasion through PI3k/Akt/mTor signaling pathway.
PMID- 25135428
TI - Down-regulation of Dicer and Ago2 is associated with cell proliferation and
apoptosis in prostate cancer.
AB - Dicer and Argonaute2 (Ago2) are critical components responsible not only for RNA
interference but also for microRNA synthesis. The present study investigated the
roles of Dicer and Ago2 in prostate cancer (Pca). First, the expression levels of
Dicer and Ago2 in Pca tissues were determined by immunohistochemistry (IHC) and
compared with pathological features. Next, RNA interference was used to down
regulate the expression levels of Dicer and Ago2 in the Pca cell lines LNCaP, PC
3, and DU145, and effects on proliferation, apoptosis, and cell cycle were
detected using the CCK-8 assay and flow cytometry, respectively. We found that
Dicer and Ago2 expression levels in Pca tissues were higher than those in
adjacent benign tissues and correlated with lower Gleason patterns, with the
exception of Dicer expression in localized Pca. In vitro, silencing Dicer or Ago2
inhibited cell proliferation and induced apoptosis in LNCaP, PC-3, and DU145, as
well as arrested the cell cycle at the G2/M phase in androgen-dependent LNCaP, or
at S phase in the androgen-independent PC-3 and DU145. Altogether these findings
suggest that Dicer and Ago2 play important roles in proliferation, apoptosis, and
the cell cycle in Pca and might serve as both promising biomarkers for Pca
progression and potential therapeutic targets.
PMID- 25135430
TI - Prognostic value of TROP2 expression in patients with gallbladder cancer.
AB - Altered expression of TROP2 is observed in various types of human cancers.
However, the clinical significance and pathological role of TROP2 in gallbladder
cancer (GBC) remains unclear. The main objective of this investigation was to
clarify the relationships between TROP2 expression and the clinicopathological
features of patients with GBC. Immunohistochemistry was performed to investigate
the expression of TROP2 and epithelial-mesenchymal transition (EMT) indicator
proteins in 93 patients with GBC. Immunohistochemistry showed that the protein
expression level of TROP2 was significantly higher in GBC tissues than in
adjacent noncancerous tissues. In addition, immunohistochemistry analysis showed
that TROP2 expression was significantly correlated with histologic grade
(P=0.038), tumor stage (P=0.015), and lymph node metastasis (P=0.007).
Furthermore, high TROP2 expression was significantly associated with a loss of
the epithelial marker E-cadherin (P=0.013) and acquisition of expression of the
mesenchymal marker vimentin (P=0.031). Kaplan-Meier analysis and Cox proportional
hazards regression models were used to investigate the correlation between TROP2
expression and prognosis of GBC patients. Kaplan-Meier analysis indicated that
patients with high TROP2 expression had poor overall survival (P<0.001).
Multivariate analysis showed that high TROP2 expression was an independent
predictor of overall survival. In conclusion, our data suggest for the first time
that the increased expression of TROP2 in GBC is associated significantly with
aggressive progression and poor prognosis. In conclusion, this study confirmed
that TROP2 might be involved in regulating the EMT and malignant progression in
GBC. It also provided the first evidence that TROP2 expression in GBC was an
independent prognostic factor of patients, which might be a potential diagnostic
and therapeutic target of GBC.
PMID- 25135431
TI - Lgr5-positive cells are cancer stem cells in skin squamous cell carcinoma.
AB - Cancer stem cells (CSCs) in most human tumors are commonly identified and
enriched using similar strategies for identifying normal stem cells, including
flow cytometry assays for side population, high aldehyde dehydrogenase (ALDH)
activity, and CD133 positivity. Thus, development of a method for isolating a
specific cancer using cancer-specific characteristic appears to be potentially
important. Here, we reported extremely high Lgr5 levels in the specimen from skin
squamous cell carcinoma (SCC) in patients. Using SCC cell line A431, we detected
high Lgr5 and CD133 levels in ALDH-high or side population from these cancer
cells. To figure out whether Lgr5 is a marker of CSCs in SCC, we transfected A431
cells with a Lgr5-creERT-2A-DTR/Cag-Loxp-GFP-STOP-Loxp-RFP plasmid and purified
transfected cells (tA431) based on GFP by flow cytometry. 4-Hydroxytamoxifen (4
OHT) was given to label Lgr5-positive cells with RFP, for comparison to GFP
positive Lgr5-negative cells. Lgr5-positive cells grew significantly faster than
Lgr5-negative cells, and the fold increase in growth of Lgr5-positive vs Lgr5
negative cells is significantly higher than SP vs non-SP, or ALDH-high vs ALDH
low, or CD133-positive vs CD133-negative cells. Moreover, in Lgr5-negative
population, Lgr5-positive re-appeared in culture with time, suggesting that Lgr5
positive cells can be regenerated from Lgr5-negative cells. Furthermore, the
growth of tA431 cells significantly decreased upon a single dose of diphtheria
toxin (DT)/4-OHT to eliminate Lgr5-positive cell lineage, while multiple doses of
DT/4-OHT nearly completely inhibited tA431 cell growth. Taken together, our data
provide compelling data to demonstrate that Lgr5-positive cells are CSCs in skin
SCC.
PMID- 25135432
TI - A two-qubit photonic quantum processor and its application to solving systems of
linear equations.
AB - Large-scale quantum computers will require the ability to apply long sequences of
entangling gates to many qubits. In a photonic architecture, where single-qubit
gates can be performed easily and precisely, the application of consecutive two
qubit entangling gates has been a significant obstacle. Here, we demonstrate a
two-qubit photonic quantum processor that implements two consecutive CNOT gates
on the same pair of polarisation-encoded qubits. To demonstrate the flexibility
of our system, we implement various instances of the quantum algorithm for
solving of systems of linear equations.
PMID- 25135433
TI - Photocatalytic generation of solar fuels from the reduction of H2O and CO2: a
look at the patent literature.
AB - The application of photocatalysis in environment remediation as well as in the
generation of useful fuels from the reduction of water (hydrogen) and of carbon
dioxide (methanol, carbon monoxide and/or methane) has been investigated largely
in the last four decades. A significant part (12-13%) of the literature on the
generation of such fuels is found in patents. Accordingly, the present article
presents a selection of the patent literature on the theme. Photocatalysts,
whether pure or doped, solid solutions or composites, reported in patents are
reviewed along with the corresponding preparative methods and the photocatalytic
performance. The absorption of light by such materials has been extended toward
the red side of the spectrum, so that a better use of solar irradiation has been
obtained, but the expected improvement of the catalytic effect has not always
been achieved. The causes of these results and the way for improving the
performance in the various steps of the process (e.g. avoiding charge
recombination or catalyst corrosion) have been documented. The correct use of the
term water splitting and the fundamentals of photochemical hydrogen evolution in
the presence of a sacrificial electron donor (e.g., alcohols) are discussed.
Quantitative data about the amount of hydrogen evolved or carbon-based fuels
produced are indicated whenever available.
PMID- 25135434
TI - An evaluation of the independence of the Health of the Nation Outcome Scales.
AB - OBJECTIVE: In this study the independence of the scales/items in the Health of
the Nation Outcome Scales (HoNOS) was empirically investigated. METHOD: Parallel
analysis using random column permutation and bootstrapping were used to compare
the factor structure, intercorrelations and Cronbach's alpha from the original
HoNOS study and also recently collected HoNOS ratings. Random permutation ensures
that the data has the same distributions as the data it is based on, but that the
variables are now independent. RESULTS: It is shown that both of the real HoNOS
data sets are significantly different to the independent items data in many ways.
An examination of fit statistics from confirmatory factor analysis is also used
to show that the independence model is a very poor fit to the data. CONCLUSIONS:
It is clear that the 12 HoNOS scales are unlikely to be independent. There is a
need for more research to clarify the appropriate structure of HoNOS, and also to
consider whether some of the items need either replacing or augmenting.
PMID- 25135435
TI - Dosing and effectiveness of ketamine anesthesia for electroconvulsive therapy
(ECT): a case series.
AB - OBJECTIVE: To provide additional data about the clinical efficacy and dosing
range for ketamine used as the induction agent in electroconvulsive therapy
(ECT). METHOD: We reviewed the clinical data in our academic hospital ECT service
over the last four years for patients who had received ketamine as the sole, or
adjunctive, anesthesia induction agent. We extracted clinical data about
antidepressant response as well as absolute and weight-based dosing for ketamine.
RESULTS: We found nine patients who were treated with ketamine as the anesthetic
at some point during the course of their treatment (eight as the sole agent, one
as adjunctive). The median induction dose for ketamine was 1.1 mg/kg. For most
patients, there was demonstrable clinical benefit. CONCLUSIONS: Ketamine has a
role as an alternative induction anesthetic agent in ECT. Our case series adds to
the literature on the concomitant use of ECT and ketamine.
PMID- 25135437
TI - Medicalisation by non-medical personnel in English literature.
AB - OBJECTIVE: To determine whether English literature contains depictions of
medicalisation by non-medical people. METHOD: English literature was examined by
us and skilled readers. RESULTS: We identified four examples: two from Macbeth
and two from Vanity Fair. Not only were non-medical people the instigators, but
in each publication there is one example of the advice of a medical professional
(whom denied the existence of a medical problem) opinion being rejected.
CONCLUSIONS: Evidence from the work of respected authors indicates that
medicalisation was practiced long before it was described in the 1970s, that it
may be instigated by non-medical people, and that it may continue after medical
professionals deny the existence of medical problems.
PMID- 25135436
TI - Madness at the movies: prioritised movies for self-directed learning by medical
students.
AB - OBJECTIVE: We aimed to systematically compile a list of 10 movies to facilitate
self-directed learning in psychiatry by medical students. METHOD: The selected
areas were those of the top five mental health conditions from the Global Burden
of Disease 2010 study. The search strategy for movies covered an extensive range
of sources (published literature and websites), followed by closer examination
and critical viewing of a sample. RESULTS: Out of a total of 503 potential movies
that were identified, 23 were selected for viewing and more detailed critique.
The final top 10 were: for depressive and anxiety disorders: Ordinary People
(1980), Silver Linings Playbook (2012); for illicit drug use: Trainspotting
(1996), Winter's Bone (2010), Rachel Getting Married (2008), Half Nelson (2006);
for alcohol use disorders: Another Year (2010), Passion Fish (1992); and for
schizophrenia: The Devil and Daniel Johnston (2006), and An Angel at My Table
(1990). CONCLUSIONS: The final selection of 10 movies all appeared to have
relatively high entertainment value together with rich content in terms of
psychiatric themes. Further research could evaluate the extent to which medical
students actually watch such movies, by assessing the level of withdrawals from a
medical school library and surveying student responses.
PMID- 25135438
TI - Modulating the magnetic properties by structural modification in a family of Co
Ln (Ln = Gd, Dy) molecular aggregates.
AB - Two types of heterometallic aggregates of the general formula
[(Co(II))3(Co(III))2Ln3(MU3-OH)5(O2C(t)Bu)12(L)2].2H2O (Ln = Gd(III) (), Dy(III)
()) and [(Co(III))3Ln3(MU3-OH)4(O2C(t)Bu)6(L)3](NO3)2.2CH3CN.2H2O (Ln = Gd(III)
(), Dy(III) ()) were successfully isolated in reactions with [Co2(MU
OH2)(O2C(t)Bu)4].(HO2C(t)Bu)4, Ln(NO3)3 and n-N-butyldiethanolamine (H2L) under
ambient conditions by a change in the stoichiometry of the reactants from 1 : 1 :
1 to 1 : 1 : 2 in order. Bond Valence Sum (BVS) calculations and bond lengths
indicate the presence of mixed valent Co (Co(II), Co(III)) centres in compounds
and and only Co(III) centres in and as required for the charge balances and
supported by the magnetic measurements. Isostructural crab shaped complexes and
feature distorted cubane cores that edge share to each other whereas the metallic
core of or displays hemicubane like arrangement of metal centres and oxygen
atoms. Overall structural symmetry was found to enhance on moving from the former
to the latter series of complexes. Magnetic studies reveal significant magnetic
entropy changes for complexes and (-DeltaSm = 21.57 and 19.39 J kg(-1) K(-1)) and
single molecular magnetic behaviour for and .
PMID- 25135439
TI - Vaginal displacement during course of adjuvant radiation for cervical cancer:
results from a prospective IG-IMRT study.
AB - OBJECTIVE: To compare internal target volume (ITV) generated using population
based displacements (ITV_study) with empty and full bladder scan fusion
(ITV_EBFB) for organ-at-risk (OAR) doses during adjuvant intensity-modulated
radiation therapy (IMRT) for cervical cancer. METHODS: From January 2011 to
October 2012, patients undergoing IMRT were included. CT simulation was carried
out after inserting vault markers. Planning target volume (PTV)_EBFB received 50
Gy per 25 fractions. Pre-treatment megavoltage CT (MVCT) was performed. MVCTs
were registered using bony landmarks with Day 1 MVCT. Displacement of the centre
of mass of markers was measured along each axis. Directional ITV was calculated
using mean +/- 2 standard deviations (SDs) (ITV_study). Replanning was performed
using PTV study, and OAR doses were compared with PTV_EBFB using Wilcoxon test.
RESULTS: A total of 348/386 data sets were evaluable for 16 patients. The median
vaginal displacement was 1.2 mm (SD, 1.3 mm), 4.0 mm (SD, 3.5 mm) and 2.8 mm (SD,
3.3 mm) in the mediolateral, superoinferior and anteroposterior directions,
respectively. The ITV margins were 4.1, 10.3 and 10.6 mm. ITV_study and ITV_EBFB
were 115.2 cm(3) (87.7-152.2 cm(3)) and 151 cm(3) (95.7-277.1 cm(3)) (p <
0.0001), respectively. PTV_study and PTV_EBFB were 814 and 881 cm(3) (p <
0.0001), respectively. Median doses to the bladder were lower with the PTV_study
(46.2 Gy vs 43.2 Gy; p = 0.0001), and a similar trend was observed in the volume
of the small bowel receiving 40 Gy (68.2 vs 60.1 cm(3); p = 0.09). CONCLUSION:
Population-based PTV margins can lead to reduction in OAR doses. ADVANCES IN
KNOWLEDGE: Population-based ITV may reduce OAR doses while executing adjuvant
IMRT for cervical cancer.
PMID- 25135440
TI - Conversion of waste polypropylene to liquid fuel using acid-activated kaolin.
AB - Waste polypropylene was subjected to thermal degradation in the presence of
kaolin and acid-treated kaolin, with different catalyst-to-plastics ratios, in a
semi-batch reactor at a temperature range of 400-550 degrees C to obtain
optimized process conditions for the production of liquid fuels. The effects of
process temperature, catalyst and feed composition on yield and quality of the
oil were determined. For a thermal decomposition reaction at up to 450 degrees C,
the major product is volatile oil; and the major products at a higher temperature
(475-550 degrees C) are either viscous liquid or wax. The highest yield of
condensed fraction in the thermal reaction is 82.85% by weight at 500 degrees C.
Use of kaolin and acid-treated kaolin as a catalyst decreased the reaction time
and increased the yield of liquid fraction. The major product of catalysed
degradation at all temperatures is highly volatile liquid oil. The maximum oil
yield using kaolin and acid-treated kaolin is 87.5% and 92%, respectively, at 500
degrees C. The oil obtained was characterized using GC-MS for its composition and
different fuel properties by IS methods.
PMID- 25135441
TI - Paclitaxel-eluting nanofiber-covered self-expanding nonvascular stent for
palliative chemotherapy of gastrointestinal cancer and its related stenosis.
AB - Self-expanding non-vascular metal stents (SEMS) is now a choice of treatment for
tumor-induced obstructive symptoms of gastrointestinal tract. But in-growing
tumor causes re-stenosis. Here, we studied a paclitaxel-eluting nanofiber-covered
stent for palliative chemotherapy of gastrointestinal cancer and its related
stenosis. In vivo and in vitro feasibility of nanofiber-covered nonvascular stent
was evaluated in this study. Nanofiber-covered stent released paclitaxel (PTX) in
controlled manner for 30 days. PTX-NFM significantly inhibited the growth of CT
26 colon cancer in comparison with PTX injection. PTX maintained higher tumor
concentrations over 1.0 MUg/ml for more than 14 days without systemic exposure.
TUNEL and H&E staining proved locally concentrated PTX induced the higher
apoptosis than PTX injection. In this way, PTX-eluting nanofiber-covered stent
possibly inhibits in-growth of cancer and extends patency of stent. Clinical
feasibility of PTX-eluting nanofiber nonvascular stent for cholangiocarcinoma and
gastrointestinal cancers will be investigated in further studies.
PMID- 25135442
TI - Mid- and long-term outcomes of carotid-cavernous fistula endovascular management
with Onyx and n-BCA: experience of a single tertiary center.
AB - INTRODUCTION: Endovascular therapy is the preferred treatment for most carotid
cavernous fistulas (CCFs). Early reports have documented excellent initial
clinical and radiographic outcomes after embolization of CCFs with Onyx or n
butyl cyanoacrylate (n-BCA), but little evidence is available about the long-term
durability of this technique. OBJECTIVE: To characterize the long-term durability
of CCF liquid embolization. METHODS: The authors retrospectively reviewed a
database of 24 CCFs in 21 consecutive patients who underwent Onyx or n-BCA
embolization of a CCF from 2006 to 2013 at our institution. RESULTS: A total of
25 Onyx or n-BCA embolization procedures were attempted and 24 successfully
completed during the study, resulting in complete or near-complete occlusion by
the end of the study in all 24 CCFs (obliteration success, 100%). Attempted
embolization in a single CCF failed initially, but was performed successfully at
a later date by a different approach. None of the 24 CCFs recanalized, regrew, or
required any further treatment subsequent to Onyx or n-BCA embolization
throughout a mean 12.4 months of angiographic follow-up (range 1-36 months).
Clinically significant complications were seen in three embolization procedures,
including cranial nerve palsies (n=1), embolic infarct (n=1), and intraperitoneal
hemorrhage (n=1). CONCLUSIONS: Early evidence has indicated that endovascular
embolization with Onyx is relatively safe and effective at achieving an initial
angiographic cure for CCFs. Results of our series suggest that angiographic and
clinical outcomes of Onyx and n-BCA embolization remain stable at mid- and long
term follow-up.
PMID- 25135443
TI - Endoscopic anterior fundoplication with the Medigus Ultrasonic Surgical
Endostapler (MUSETM) for gastroesophageal reflux disease: 6-month results from a
multi-center prospective trial.
AB - BACKGROUND: Both long-term proton pump inhibitor (PPI) use and surgical
fundoplication have potential drawbacks as treatments for chronic
gastroesophageal reflux disease (GERD). This multi-center, prospective study
evaluated the clinical experiences of 69 patients who received an alternative
treatment: endoscopic anterior fundoplication with a video- and ultrasound-guided
transoral surgical stapler. METHODS: Patients with well-categorized GERD were
enrolled at six international sites. Efficacy data was compared at baseline and
at 6 months post-procedure. The primary endpoint was a >= 50 % improvement in
GERD health-related quality of life (HRQL) score. Secondary endpoints were
elimination or >= 50 % reduction in dose of PPI medication and reduction of total
acid exposure on esophageal pH probe monitoring. A safety evaluation was
performed at time 0 and weeks 1, 4, 12, and 6 months. RESULTS: 66 patients
completed follow-up. Six months after the procedure, the GERD-HRQL score improved
by >50 % off PPI in 73 % (48/66) of patients (95 % CI 60-83 %). Forty-two
patients (64.6 %) were no longer using daily PPI medication. Of the 23 patients
who continued to take PPI following the procedure, 13 (56.5 %) reported a >= 50 %
reduction in dose. The mean percent of total time with esophageal pH <4.0
decreased from baseline to 6 months (P < 0.001). Common adverse events were peri
operative chest discomfort and sore throat. Two severe adverse events requiring
intervention occurred in the first 24 subjects, no further esophageal injury or
leaks were reported in the remaining 48 enrolled subjects. CONCLUSIONS: The
initial 6-month data reported in this study demonstrate safety and efficacy of
this endoscopic plication device. Early experience with the device necessitated
procedure and device changes to improve safety, with improved results in the
later portion of the study. Continued assessment of durability and safety are
ongoing in a three-year follow-up study of this patient group.
PMID- 25135444
TI - Robotic-assisted lateral lymph node dissection for lower rectal cancer: short
term outcomes in 50 consecutive patients.
AB - BACKGROUND: The goal of this study was to evaluate the short-term outcomes of
robotic-assisted lateral lymph node dissection for patients with advanced lower
rectal cancer. METHODS: Between 2012 and 2013, 50 consecutive patients underwent
robotic-assisted lateral lymph node dissection for rectal cancer in Shizuoka
Cancer Center Hospital. Perioperative outcomes including operative time,
operative blood loss, length of stay, postoperative complications, and
histopathological data were collected prospectively. RESULTS: Median patient age
was 62 years (range 36-74 years). Operative procedures included low anterior
resections (n = 27), intersphincteric resections (n = 16), and abdominoperineal
resections (n = 7). Bilateral lymph node dissection was performed in 44 patients.
The median operative time was 476 min (range 320-683 min), and the median time
required for lateral lymph node dissection was 165 min (range 85-257 min). The
median blood loss was 27 mL (range 5-690 mL). There were no cases of open surgery
or laparoscopic conversion. The median duration of postoperative hospital stay
was 8 days (range 6-13 days). Clavien-Dindo classification Grade III-IV
complications occurred in only one patient (2.0 %). There were no cases of
anastomotic leak. There was no perioperative mortality. The median number of
harvested lateral lymph nodes was 19 (range 5-47). CONCLUSIONS: Robotic-assisted
lateral lymph node dissection is a safe, feasible, and useful approach for
patients with advanced lower rectal cancer.
PMID- 25135445
TI - Cranial-to-caudal approach for radical lymph node dissection along the surgical
trunk in laparoscopic right hemicolectomy.
AB - Complete mesocolic excision with central vascular ligation is considered to
contribute to superior oncological outcomes after colon cancer surgery [1]. For
advanced right-sided colon cancer, this surgery sometimes requires lymph node
(LN) dissection along the superior mesenteric vein (SMV), with division of the
middle colic vessels, or their right branches, at origin [2]. Here, we present
cranially approached radical LN dissection along the surgical trunk during
laparoscopic right hemicolectomy. The omental bursa is first opened wide, and the
gastrocolic trunk of Henle is exposed, using the right gastroepiploic vessels and
the accessory right colic vein (ARCV) as landmarks. After division of ARCV, SMV
and middle colic vein (MCV) are identified. After dividing MCV at its root, LN
dissection along SMV is conducted in a cranial-to-caudal manner. Concurrently,
the middle colic artery, or its right branch, is exposed and divided at origin.
The transverse colon is then raised ventrally, and LN dissection along SMV using
a cranial-to-caudal approach is again performed. The ileocolic and right colic
vessels are divided at origin. The ascending and transverse mesocolon, including
the pedicles, are then separated from the retroperitoneal tissues, pancreatic
head, and duodenum, using a medial approach. The key characteristics in this
procedure consist of easy access to pancreas, early division of ARCV and middle
colic vessels at origin, and easy dissection along SMV. We performed a
laparoscopic colectomy using this approach for 18 patients with right-sided colon
cancer. The mean operative time and blood loss were 288 min and 83 ml,
respectively. The mean number of harvested LNs was 24. There were 6 cases with
positive LN metastasis. There were no recurrent cases at a median follow-up
period of 24 months. We consider this approach to be safe and useful for radical
LN dissection along SMV for right-sided colon cancers.
PMID- 25135446
TI - Ultrasound-guided laparoscopic liver resections.
AB - BACKGROUND: Intraoperative liver ultrasound has an established role in liver
surgery to complete staging and to guide resection. The same performances should
be expected by laparoscopic ultrasound (LUS). METHODS: LUS is first performed to
identify relationships between tumor and vasculo-biliary pedicles. The planes
where the main vascular structures run are marked on the liver surface.
Parenchymal transection is performed and each vessel recognized during LUS
exploration is divided. RESULTS: From 01/2009 to 10/2013, in 61 out of 742 liver
resections (8.2 %), a laparoscopic approach was attempted. The conversion rate
was 9.8 % (six patients). No conversion was related to bleeding or intraoperative
complications. The remnant 55 patients were affected by benign lesions in 11
cases and malignant tumors in 44. The resections included 3 left hepatectomies,
14 bisegmentectomies Sg2-3, 5 segmentectomies, and 38 wedge resections.
Associated procedures were performed in eight patients (14.5 %), including four
colorectal resections. Median duration of surgery was 150 min (60-345 min).
Median operative blood loss was 100 mL (0-500 mL). Median size of resected tumor
was 2.5 cm (0.9-8 cm). Median surgical margin in oncological resections was 7 mm
(0-50 mm). Postoperative complications occurred in four patients (7.2 %), all
grade 2 according to Dindo classification. No liver-related morbidity occurred.
Median length of hospital stay was 5 days (3-9 days). CONCLUSIONS: Ultrasound
guided liver resections can be performed by laparoscopic approach with the same
accuracy than open surgery.
PMID- 25135447
TI - Red blood cell folate as a risk factor for breast cancer among patients at a
tertiary hospital in Uganda: a case control study.
AB - BACKGROUND: Folate has been shown to play a complex but unclear role in
carcinogenesis, with some studies showing that low folate intake protects against
early carcinogenesis while high folate intake promotes advanced carcinogenesis.
Other studies have shown that high folate is associated with decreased breast
cancer risk and overall survival, yet others found no such association.This study
therefore sought to determine the association between red blood folate levels and
breast cancer among women seen at a tertiary Ugandan hospital. METHODS: A case
control study was conducted where female patients with a histological diagnosis
of breast cancer were recruited as cases, and females without cancer attending
other surgical clinics as controls. Demographics and social behavior data were
collected and 5 mls of blood drawn for laboratory testing of red blood cell (RBC)
folate, serum vitamin B12 and RBC count. Ethical approval was obtained. RESULTS:
In this study, a total of 145 women were recruited as 72 cases and 73 controls.
The odds of having breast cancer among women with normal folate levels compared
to those with low folate levels were 1.4 (95% CI 0.7 to 2.9) P = 0.290. Ninety
participants (63%) had low RBC folate and 53 participants (37%) had normal RBC
folate. Thirty five (45%) of the women from a rural setting had normal folate
levels compared to 18(28%) women from an urban setting. CONCLUSIONS: There was no
significant association found between RBC folate and breast cancer among this
group of women in Uganda.
PMID- 25135448
TI - Windrow composting mitigated CH4 emissions: characterization of methanogenic and
methanotrophic communities in manure management.
AB - With increasing livestock breeding, methane (CH4 ) emissions from manure
management will increasingly contribute more to atmospheric CH4 concentration.
The dynamics of methanogens and methanotrophs have not yet been studied in the
manure environment. The current study combines surface CH4 emissions with
methanogenic and methanotrophic community analyses from two management practices,
windrow composting (WCOM) and solid storage (SSTO). Our results showed that there
was an c. 50% reduction of CH4 emissions with WCOM compared with SSTO over a 50
day period. A sharp decrease in the quantities of both methanogens and
methanotrophs in WCOM suggested that CH4 mitigation was mainly due to decreased
CH4 production rather than increased CH4 oxidation. Pyrosequencing analysis
demonstrated that aeration caused a clear shift of dominant methanogens in the
manure, with specifically a significant decrease in Methanosarcina and increase
in Methanobrevibacter. The composition of methanogenic community was influenced
by manure management and regulated CH4 production. A sharp increase in the
quantity of methanotrophs in SSTO suggested that microbial CH4 oxidation is an
important sink for the CH4 produced. The increased abundance of Methylococcaceae
in SSTO suggested that Type I methanotrophs have an advantage in CH4 oxidation in
occupying niches under low CH4 and high O2 conditions.
PMID- 25135449
TI - DMSO induced myocardial infarction during allogeneic cryopreserved bone marrow
transplant.
PMID- 25135450
TI - Early CMV replication and subsequent chronic GVHD have a significant anti
leukemic effect after allogeneic HSCT in acute myeloid leukemia.
AB - Early cytomegalovirus (CMV) replication (eCMV) after allogeneic hematopoietic
stem cell transplantation (allo-HSCT) has been suggested as an independent factor
that reduces leukemia relapse risk. We retrospectively analyzed 74 patients with
acute myeloid leukemia (AML) who underwent allo-HSCT between August 2006 and
September 2012. All recipients were CMV seropositive. In 52 patients, eCMV
occurred at a median of 35 days (range, 11-92) after allo-HSCT. Univariate
analysis revealed that the factors associated with a reduction in the 5-year
cumulative incidence of relapse (CIR) included the first complete remission
status at allo-HSCT, non-adverse cytogenetics and molecular abnormalities, pre
transplant serum ferritin level <1,400 mg/dL, chronic graft-versus-host disease
(cGVHD), and eCMV. In sub-group analysis, according to the existence of eCMV and
cGVHD, those with both eCMV and cGVHD showed the lowest 5-year CIR (P < 0.003).
Patients with both eCMV and cGVHD had the best outcome for leukemia-free survival
(LFS) (P < 0.001) and OS (P < 0.001). In the CMV-seropositive population, the
presence of eCMV in combination with cGVHD had a significant positive effect on
LFS and OS after allo-HSCT. When eCMV preceded cGVHD, the relapse rate after allo
HSCT was significantly reduced in patients with AML. Therefore, we suggest that
it is critical to have an immunological understanding of the graft-versus
leukemia effect in this setting.
PMID- 25135451
TI - Preexisting TP53 mutation in therapy-related acute myeloid leukemia.
PMID- 25135453
TI - Optimization of niosomes for enhanced antibacterial activity and reduced
bacterial resistance: in vitro and in vivo evaluation.
AB - OBJECTIVE: The aim was to optimize norfloxacin niosomes for enhanced
antibacterial activity and reduced bacterial resistance. METHODS: Pseudomonas
aeruginosa, a biofilm forming bacterium, was used as the test organism. Different
norfloxacin niosomes were evaluated in vitro and in vivo, respectively, for
antibacterial activity compared with aqueous drug solution. The influence of
norfloxacin niosomes on biofilm formation was investigated. The interaction of
niosomes with bacterial cells was also monitored using the scanning electron
microscopy (SEM). RESULTS: The efficacy of niosomes depended on their
composition. Standard niosomes of Span 60 and cholesterol were similar to drug
solution. Incorporation of Tween 80, oleic acid (OA), OA/propylene glycol or
lecithin produced fluid niosomes which reduced the MIC and inhibited biofilm
formation compared with drug solution. Incorporation of a positively charged
agent into fluid niosomes enhanced the antibacterial activity and reduced biofilm
formation significantly. SEM showed evidence of vesicle adsorption to the
bacteria with possible adhesion or fusion with the cell membrane. The in vivo
skin model confirmed the in vitro results with optimum niosomes being more
efficient than drug solution. CONCLUSION: Niosomes are promising for enhanced
antibacterial activity and reduced resistance to antibiotics. The later can be
achieved by inhibition of biofilm formation.
PMID- 25135452
TI - Role of lenalidomide in the management of myelodysplastic syndromes with del(5q)
associated with pure red cell aplasia (PRCA).
PMID- 25135454
TI - A psychometric evaluation of the Icelandic version of the WHO-5.
AB - The psychometric properties of the Icelandic version of the World Health
Organization five wellbeing index (WHO-5) were evaluated using two samples, a
randomly selected sample (N = 3,896) from the Icelandic National Registry and a
convenience sample of primary care patients (N = 126). The factor structure of
the scale was tested with confirmatory factor analysis (CFA). The correlation
between the WHO-5 and other measures of depression and anxiety were calculated to
assess the scale's convergent and divergent validity. The discriminant validity
of the WHO-5 was explored with a receiver operating analysis compared to the Mini
International Neuropsychiatric Interview. The CFA indicated that the factor
structure of the WHO-5 was one-dimensional and factorial invariant between
groups. The internal reliability of the WHO-5 was adequate and the convergent,
divergent and discriminant validity of the WHO-5 was supported. It is concluded
that the psychometric properties of the Icelandic version of the WHO-5 are
satisfactory.
PMID- 25135455
TI - Testing for beneficial reversal of dominance during salinity shifts in the
invasive copepod Eurytemora affinis, and implications for the maintenance of
genetic variation.
AB - Maintenance of genetic variation at loci under selection has profound
implications for adaptation under environmental change. In temporally and
spatially varying habitats, non-neutral polymorphism could be maintained by
heterozygote advantage across environments (marginal overdominance), which could
be greatly increased by beneficial reversal of dominance across conditions. We
tested for reversal of dominance and marginal overdominance in salinity tolerance
in the saltwater-to-freshwater invading copepod Eurytemora affinis. We compared
survival of F1 offspring generated by crossing saline and freshwater inbred lines
(between-salinity F1 crosses) relative to within-salinity F1 crosses, across
three salinities. We found evidence for both beneficial reversal of dominance and
marginal overdominance in salinity tolerance. In support of reversal of
dominance, survival of between-salinity F1 crosses was not different from that of
freshwater F1 crosses under freshwater conditions and saltwater F1 crosses under
saltwater conditions. In support of marginal overdominance, between-salinity F1
crosses exhibited significantly higher survival across salinities relative to
both freshwater and saltwater F1 crosses. Our study provides a rare empirical
example of complete beneficial reversal of dominance associated with
environmental change. This mechanism might be crucial for maintaining genetic
variation in salinity tolerance in E. affinis populations, allowing rapid
adaptation to salinity changes during habitat invasions.
PMID- 25135456
TI - Substrate-modified functional group reactivity: hasubanan and acutumine alkaloid
syntheses.
AB - Functional group taxonomy provides a powerful conceptual framework to classify
and predict the chemical reactivity of molecular structures. These principals are
most effective in monofunctional settings, wherein individual functional groups
can be analyzed without complications. In more complex settings, the predictive
value of these analyses decreases as alternative reaction pathways, promoted by
neighboring substituents and aggregate molecular properties, emerge. We refer to
this phenomenon as substrate-modified functional group reactivity. In this
Perspective, we explain how substrate-modified functional group reactivity molded
our synthetic routes to the hasubanan and acutumine alkaloids. These
investigations underscore the potential for discovery and insight that can only
be gained by studying the reactivity of complex multifunctional structures.
PMID- 25135457
TI - Interpreting carbonate and organic carbon isotope covariance in the sedimentary
record.
AB - Many negative delta(13)C excursions in marine carbonates from the geological
record are interpreted to record significant biogeochemical events in early Earth
history. The assumption that no post-depositional processes can simultaneously
alter carbonate and organic delta(13)C values towards more negative values is the
cornerstone of this approach. However, the effects of post-depositional
alteration on the relationship between carbonate and organic delta(13)C values
have not been directly evaluated. Here we present paired carbonate and organic
delta(13)C records that exhibit a coupled negative excursion resulting from
multiple periods of meteoric alteration of the carbonate delta(13)C record, and
consequent contributions of isotopically negative terrestrial organic matter to
the sedimentary record. The possibility that carbonate and organic delta(13)C
records can be simultaneously shifted towards lower delta(13)C values during
periods of subaerial exposure may necessitate the reappraisal of some of the
delta(13)C anomalies associated with noteworthy biogeochemical events throughout
Earth history.
PMID- 25135458
TI - Changes in pig diet particle size profile and nutrient content during on-farm
storage and distribution to the feeders.
AB - The present study assessed the effect of silo emptying and feed transport by
conveyor systems on particle size and nutrient content of the feed delivered to
the pigs. Experiment 1 sampled feed from four feeders along the conveyor system
of two barns. Samples were taken immediately after filling the feed silo (Begin)
and when the silo was almost empty (End). In Experiment 2, three barns with drag
type conveyors, three with auger-type conveyors and two with spiral-type
conveyors were sampled. Along the different conveyors, samples at 10, 20, 50 and
85 m distance from the feed silo were taken from the feeders. In each barn,
sampling was repeated for two subsequent batches of feed delivered. In all
samples, particle size profile was determined and nutrient content was analysed.
In Experiment 2, mineral content was also determined. In Experiment 1, the size
of the different particle fractions decreased from Begin to End. An interaction
(p < 0.05) between sampling time and conveyor type was detected for the 10%
smallest particles. In Experiment 2, an effect of sampling time on the 10%
largest particles was detected (p < 0.05). The effect of sampling time on several
nutrients was observed in Experiments 1 and 2, but the affected nutrients
differed between both experiments. Results implied that it was mainly emptying of
the silo that affected mash particle size profile and nutrient content. The
potential impact of these changes on pig performance requires further
investigation.
PMID- 25135459
TI - Secondary damage in left-sided frontal white matter detected by diffusion tensor
imaging is correlated with executive dysfunction in patients with acute
infarction at the ipsilateral posterior corona radiata.
AB - BACKGROUND: Executive dysfunction has been observed in patients with left-sided
anterior corona radiata infarction. However, whether left-sided posterior corona
radiata infarction could cause executive dysfunction is unclear. Also, whether
secondary damage in the left frontal white matter following ipsilateral posterior
corona radiata infarct is causal or not and contributes to the occurrence and
development of executive dysfunction, is still uncertain. METHODS: Twelve
patients with posterior corona radiata infarction underwent diffusion tensor
imaging (DTI) and an executive functional assessment at week 1 (W1), week 4 (W4),
and week 12 (W12) after onset. Color duplex sonography and Transcranial Duplex
Scanning (TCD) were performed at W1 and W12. Twelve healthy volunteers of similar
ages and educational histories were examined as controls and assessed once.
RESULTS: In the patients, we observed an increased mean diffusivity (MD) and a
decreased fractional anisotropy (FA) in the left frontal white matter from W1 to
W12. There were no significant changes in cerebral blood flow in patients between
W1 and W12 according to the result of Color duplex sonography and TCD. Patients
showed progressively impaired executive function during 12 weeks. Significant
correlations were found between increased MD and decreased FA in the left frontal
white matter with impaired degree of executive function. CONCLUSIONS: This study
demonstrates that DTI detected secondary damage in left-sided frontal white
matter in patients with acute infarction at the ipsilateral posterior corona
radiata. This change may be correlated with executive functional changes in these
patients.
PMID- 25135460
TI - Panoramic radiography measurements, osteoporosis diagnoses and fractures in
Japanese men and women.
AB - OBJECTIVES: The purpose of this study was to investigate the association of the
shape of the mandibular cortex on panoramic radiographs with the risk of an
osteoporosis diagnosis without prevalent fractures and with the risk of
osteoporotic fractures in Japanese men and women. SUBJECTS AND METHODS: One
thousand and twenty-one subjects aged 40-89 years, who visited our university
hospital and underwent panoramic radiography between 2007 and 2013, participated
in this study. Eighty-eight patients received a diagnosis of osteoporosis without
prevalent fractures, and 55 were diagnosed with osteoporotic fractures. Blinded
to the groupings, we classified the shape of the mandibular cortex on panoramic
radiographs as normal, moderately eroded or severely eroded. RESULTS: After
adjustment for confounding factors, the odds ratios for an osteoporosis diagnosis
associated with moderately eroded and severely eroded mandibular cortices were
1.4 (95% CI, 0.8-2.6) and 2.6 (95% CI, 1.4-5.0), respectively. The odds ratios
for an osteoporotic fracture associated with moderately eroded and severely
eroded cortices were 0.8 (95% CI, 0.4-1.7) and 1.1 (95% CI, 0.5-2.5),
respectively. CONCLUSIONS: Subjects in Japan with eroded mandibular cortices
tended to be at increased risk of osteoporosis diagnoses but not of fractures.
PMID- 25135461
TI - Late toxicity of proton beam therapy for patients with the nasal cavity, para
nasal sinuses, or involving the skull base malignancy: importance of long-term
follow-up.
AB - BACKGROUND: Although several reports have shown that proton beam therapy (PBT)
offers promise for patients with skull base cancer, little is known about the
frequency of late toxicity in clinical practice when PBT is used for these
patients. Here, we conducted a retrospective analysis to clarify the late
toxicity profile of PBT in patients with malignancies of the nasal cavity, para
nasal sinuses, or involving the skull base. METHODS: Entry to this retrospective
study was restricted to patients with (1) malignant tumors of the nasal cavity,
para-nasal sinuses, or involving the skull base; (2) definitive or postoperative
PBT (>50 GyE) from January 1999 through December 2008; and (3) more than 1 year
of follow-up. Late toxicities were graded according to the common terminology
criteria for adverse events v4.0 (CTCAE v4.0). RESULTS: From January 1999 through
December 2008, 90 patients satisfied all criteria. Median observation period was
57.5 months (range, 12.4-162.7 months), median time to onset of grade 2 or
greater late toxicity except cataract was 39.2 months (range, 2.7-99.8 months),
and 3 patients had toxicities that occurred more than 5 years after PBT. Grade 3
late toxicities occurred in 17 patients (19%), with 19 events, and grade 4 late
toxicities in 6 patients (7%), with 6 events (encephalomyelitis infection 2,
optic nerve disorder 4). CONCLUSIONS: In conclusion, the late toxicity profile of
PBT in patients with malignancy involving the nasal cavity, para-nasal sinuses,
or skull base malignancy was partly clarified. Because late toxicity can still
occur at 5 years after treatment, long-term follow-up is necessary.
PMID- 25135463
TI - 'Bio-load' and bio-type profiles of Mycobacterium avium subspecies
paratuberculosis infection in the domestic livestock population endemic for
Johne's disease: a survey of 28 years (1985-2013) in India.
AB - Bio-load and bio-profile of Mycobacterium avium subspecies paratuberculosis was
studied in the domestic livestock population of the country. Of the 23,429 farm
and farmer's animals screened, average bio-load was 23.3% (Period of study; 28
years for goats; 13 years for sheep, cattle and buffaloes). Species-wise, bio
load was 20.1, 32.7, 39.3 and 28.3% in goats, sheep, cattle and buffaloes,
respectively. Bio-load was significantly lower in time period A (P < 0.001) and B
(P < 0.03), compared with period C. Geographical zone-wise, bio-load of MAP was
significantly higher (P < 0.05) in Central zone compared with South, West, East
and North zones. Bio-load in 11 states ranged from 16.2 to 87.8%. Of 8450, 5643,
8185 and 1151 samples screened by microscopy, culture, indigenous ELISA and IS900
blood PCR, 20.0, 10.6, 35.1 and 26.6% samples were positive, respectively. Bio
load was 32.8 and 31.6% in farm and farmer's goats and sheep, respectively, and
62.1% in farmer's cattle. MAP bio-load was also monitored in four farm units
(three goats and one sheep) for breed improvement and three farm goats units for
experimental purposes at Central Institute for Research on Goats in Mathura
district. Of the 8025 goats and 1525 sheep that died from 1988 to 2013, 10.9 and
3.0% deaths were due to JD, respectively. On the basis of JD and suspected JD,
10.0 and 28.4% goats and 2.2 and 40.9% sheep, respectively were culled from the
farm units in 25 years. Microscopic examination of 214 tissues (mesenteric lymph
nodes and intestines) of 107 animals, it was observed that bio-load of MAP was
high (25.0-60.0%) in farm animals. 'Indian Bison Type' was the dominant biotype,
irrespective of domestic livestock species and the geographical zone.
PMID- 25135462
TI - Next-generation prostate-specific antigen test: precursor form of prostate
specific antigen.
AB - An urgent need exists to develop a more sophisticated screening system in order
to improve diagnostic accuracy of clinically significant cancer and also to
reduce the drawbacks of prostate-specific antigen (PSA) screening including
overdetection and overtreatment. The most promising next-generation PSA test,
which can improve the management of prostate cancer, may be proenzyme PSA
(proPSA) or precursor PSA (pPSA). proPSA has pro-leader peptide sequences of
seven or less amino acids and previous studies demonstrated that [-2]proPSA,
which contains only a 2-amino-acid propeptide leader, could be more useful not
only to distinguish between men with and without cancer, but also between tumors
with aggressive features with performance exceeding other classical PSA-related
indices including ratio of free PSA to total PSA (%f-PSA) and PSA density.
Recently, it was demonstrated that baseline [-2]proPSA-related indices were
independent factors to predict pathological reclassification at one year or
several years after entering active surveillance. Furthermore, a retrospective
study suggested that [-2]proPSA might be a useful predictive marker for future
developing clinically manifested prostate cancer as well as aggressive tumors.
ProPSA-related indices may have the potential for developing a more ideal risk
classification for men at risk for prostate cancer, with a screening system
maintaining the sensitivity of detecting clinically significant prostate cancer
while saving cost, individualized treatment strategies, and follow-up procedures
of active surveillance or active treatments. At a minimum, proPSA will be one of
the most important new markers on the prostate cancer management in the near
future.
PMID- 25135464
TI - Partial genetic characterization of peste des petits ruminants virus from goats
in northern and eastern Tanzania.
AB - Peste des petits ruminants (PPR) is an acute viral disease of small ruminants.
The disease was first reported in Tanzania in 2008 when it was confined to the
Northern Zone districts bordering Kenya. The present study was carried out to
confirm the presence of PPR virus (PPRV) in Tanzania and to establish their
phylogenetic relationships. Samples (oculonasal swabs, tissues and whole blood)
were obtained from live goats with clinical presentation suggestive of PPR and
goats that died naturally in Ngorongoro (Northern Tanzania) and Mvomero (Eastern
Tanzania) districts. The clinical signs observed in goats suspected with PPR
included fever, dullness, diarrhea, lacrimation, matting of eye lids, purulent
oculonasal discharges, cutaneous nodules, erosions on the soft palate and gums
and labored breathing. Post mortem findings included pneumonia, congestion of the
intestines, and hemorrhages in lymph nodes associated with the respiratory and
gastrointestinal systems. PPRV was detected in 21 out of 71 tested animals using
primers targeting the nucleoprotein (N) gene. Phylogenetic analysis, based on the
N gene, indicated that PPRV obtained from Northern and Eastern Tanzania clustered
with PPRV strains of Lineage III, together with PPRV from Sudan and Ethiopia. The
findings of this study indicate that there are active PPRV infections in Northern
and Eastern Tanzania, suggesting risks for potential spread of PPR in the rest of
Tanzania.
PMID- 25135465
TI - Leptospirosis in cattle: a challenging scenario for the understanding of the
epidemiology.
AB - All over the world, leptospirosis has been reported as one of the major causes of
reproductive failure in cattle and other ruminants, determining abortions,
stillbirth, weak newborns and decrease in their growth rate and milk production.
Nevertheless, despite its importance, it is still a challenging disease, from
what scarce information about epidemiology, prophylaxis and control is available
nowadays. During the last decades of the last century, many epidemiological
studies have been conducted in several countries, mainly based on serology.
According to those studies, a seroepidemiological scenario has been stated for
different regions, where different serovars were reported for cattle.
Nevertheless, a huge problem is that, when efforts are made in order to increase
the collection of local strains (isolates), it has been demonstrated that the
scenario that emerges from those studies contrasts with those previously
determined by serology. Despite the large number of serological studies
worldwide, the number of isolates is scarce. Isolation technique is a very
delicate procedure that needs no contamination, fast processing and long delay to
produce a positive result, what may corroborate to the lack of information for
the comparison between serology versus bacteriological data, mainly in developing
countries. It is noteworthy that the epidemiological scenario now acknowledged
may not represent what really occurs in many parts of the world, particularly on
those tropical regions where the disease is endemic. Consequently, the current
knowledge about epidemiology and control, as well as the available diagnostic
tools and the commercial vaccines, may not be adequate for those regions, what
leads to a frustrating scenario of endemicity and difficulties on the control of
the disease. Without a huge effort in the culturing of local strains, besides the
advances on molecular typing, leptospirosis will not be defeated and will
probably remain endemic in the developing countries, leading to important
economic hazards in animal production and risks to public health in those
regions.
PMID- 25135466
TI - Predominance of genotype 1.1 and emergence of genotype 2.2 classical swine fever
viruses in north-eastern region of India.
AB - Classical swine fever (CSF) is a highly contagious and the most important disease
of pigs worldwide.CSF is enzootic in pig herds in India and continues to cause
huge economic losses to pig farmers. Nearly 40% of the total pig population of
India is present in the north-eastern (NE) states where pig husbandry plays an
important role in the socio-economic development. Pigs reared in the backyards
are the only source of livelihood for a majority of poor tribal population in the
region. Hardly any CSF vaccination is currently being undertaken in the
unorganized pig farming in the NE region due to economic reasons and vaccine
unavailability. A thorough understanding of the current epidemiological status of
CSF is essential for the effective control of the disease in the NE region.
Hence, we carried out molecular characterization of CSFV isolates from field
outbreaks during 2011-2012 in the entire north-eastern region of India to
establish the genetic groups of prevalent CSF viruses in the region. A total of
17 CSFV isolates obtained from different parts of the NE region were
characterized by comparing the sequences of three partial genomic regions of the
virus, that is 150 nt of 5' UTR, 190 nt of E2 and 409 nt of NS5B. Of the 17 CSFV
isolates, 15 isolates belonged to 1.1 (88.2%) and two isolates (11.8%) belonged
to 2.2 subgenogroup. The genogroup 2.2 CSFV were associated with outbreaks in
Arunachal Pradesh that shares international borders with Bhutan, Myanmar and
China. Genogroup 2.2 CSFV isolated in the present study shared high level of
sequence similarity with 2.2 viruses form China, raising the possibility of virus
incursion from this region. In summary, we found a continued predominance of 1.1
subgroup and an emergence of 2.2 subgroup CSFV in NE region of India.
PMID- 25135467
TI - Epidemiology of viral pathogens of free-ranging dogs and Indian foxes in a human
dominated landscape in central India.
AB - There is an increasing concern that free-ranging domestic dog (Canis familiaris)
populations may serve as reservoirs of pathogens which may be transmitted to
wildlife. We documented the prevalence of antibodies to three viral pathogens,
canine parvovirus (CPV), canine distemper virus (CDV) and canine adenovirus
(CAV), in free-ranging dog and sympatric Indian fox (Vulpes bengalensis)
populations in and around the Great Indian Bustard Wildlife Sanctuary, in
Maharashtra, central India. A total of 219 dogs and 33 foxes were sampled during
the study period. Ninety-three percentage of dogs and 87% of foxes were exposed
to one or more of the three pathogens. Exposure rates in dogs were high: >88% for
CPV, >72% for CDV and 71% for CAV. A large proportion of adult dogs had
antibodies against these pathogens due to seroconversion following earlier
natural infection. The high prevalence of exposure to these pathogens across the
sampling sessions, significantly higher exposure rates of adults compared with
juveniles, and seroconversion in some unvaccinated dogs documented during the
study period suggests that these pathogens are enzootic. The prevalence of
exposure to CPV, CDV and CAV in foxes was 48%, 18% and 52%, respectively.
Further, a high rate of mortality was documented in foxes with serologic evidence
of ongoing CDV infection. Dogs could be playing a role in the maintenance and
transmission of these pathogens in the fox population, but our findings show that
most dogs in the population are immune to these pathogens by virtue of earlier
natural infection, and therefore, these individuals make little current or future
contribution to viral maintenance. Vaccination of this cohort will neither
greatly improve their collective immune status nor contribute to herd immunity.
Our findings have potentially important implications for dog disease control
programmes that propose using canine vaccination as a tool for conservation
management of wild carnivore populations.
PMID- 25135469
TI - Epidemiology of pulmonary hypertension and right ventricular failure in left
heart failure.
AB - Pulmonary hypertension (PH) leading to right ventricular failure (RVF) is a
common complication of left heart failure irrespective of the left ventricular
ejection fraction. PH due to left heart disease is the most common cause of PH.
The prevalence of PH and RVF in left heart failure varies depending on the
patient population studied, the method used to diagnose PH, and the hemodynamic
criteria used to define PH. Elevated left-sided filling pressure and functional
mitral regurgitation are the two major determinants of PH in left heart failure.
PH is associated with markers of disease severity, advanced symptoms, and worse
long-term outcomes including heart failure hospitalization and mortality in left
heart failure. RVF has independent, incremental prognostic value over PH for
adverse outcomes in left heart failure. PH and RVF may be potential therapeutic
targets in patients with left heart failure.
PMID- 25135468
TI - White matter involvement in chronic musculoskeletal pain.
AB - There is emerging evidence that chronic musculoskeletal pain is associated with
anatomic and functional abnormalities in gray matter. However, little research
has investigated the relationship between chronic musculoskeletal pain and white
matter. In this study, we used whole-brain tract-based spatial statistics and
region-of-interest analyses of diffusion tensor imaging data to demonstrate that
patients with chronic musculoskeletal pain exhibit several abnormal metrics of
white matter integrity compared with healthy controls. Chronic musculoskeletal
pain was associated with lower fractional anisotropy in the splenium of the
corpus callosum and the left cingulum adjacent to the hippocampus. Patients also
had higher radial diffusivity in the splenium, right anterior and posterior limbs
of the internal capsule, external capsule, superior longitudinal fasciculus, and
cerebral peduncle. Patterns of axial diffusivity (AD) varied: patients exhibited
lower AD in the left cingulum adjacent to the hippocampus and higher AD in the
anterior limbs of the internal capsule and in the right cerebral peduncle.
Several correlations between diffusion metrics and clinical variables were also
significant at a P < .01 level: fractional anisotropy in the left uncinate
fasciculus correlated positively with total pain experience and typical levels of
pain severity. AD in the left anterior limb of the internal capsule and left
uncinate fasciculus was correlated with total pain experience and typical pain
level. Positive correlations were also found between AD in the right uncinate and
both total pain experience and pain catastrophizing. These results demonstrate
that white matter abnormalities play a role in chronic musculoskeletal pain as a
cause, a predisposing factor, a consequence, or a compensatory adaptation.
PERSPECTIVE: Patients with chronic musculoskeletal pain exhibit altered metrics
of diffusion in the brain's white matter compared with healthy volunteers, and
some of these differences are directly related to symptom severity.
PMID- 25135471
TI - Experience of mechanical thrombectomy for paediatric arterial ischaemic stroke.
AB - BACKGROUND: Paediatric arterial ischaemic stroke (AIS) is an important cause of
acute neurological symptoms in children, it causes significant morbidity and is
one of the top ten causes of childhood deaths. Consensus papers have suggested
guidelines for the management of AIS in childhood, although none recommend
thrombectomy. Despite this, children within our institution have undergone
mechanical thrombectomy for large vessel occlusion. This is the first series of
mechanical thrombectomy and outcomes performed in children in the U.K. METHODS:
We describe the endovascular management of paediatric arterial ischaemic stroke
(AIS) in four children (5-15 years) with PedNIHSS > 17. RESULTS: Three had
basilar artery (BA) occlusion and one left middle cerebral artery (MCA)
occlusion. All underwent uncomplicated thrombectomy followed by intravenous
heparin. One had a successful second attempt. The BA cases underwent thrombectomy
17-36 h after symptom onset; the left MCA case <6 h after symptom onset. Modified
Rankin Scale (MRS) was 0-3, 50% had MRS 0. DISCUSSION: Adult AIS guidelines
recommend IV recombinant tissue plasminogen activator (r-tPA) within 4.5 h of
onset and intra-arterial r-tPA within 6 h; thrombectomy being reserved for
carefully selected patients. Paediatric AIS recognition is problematic, often
with delayed imaging. There is little evidence regarding efficacy of thrombectomy
for paediatric AIS. Our experience suggests there may be a role for endovascular
clot retrieval in selected patients managed by an experienced multidisciplinary
team. Careful data collection is mandatory.
PMID- 25135470
TI - The acute cardiorenal syndrome: burden and mechanisms of disease.
AB - Worsening renal function during the treatment of acute decompensated heart
failure, so-called acute cardio-renal syndrome, is very common and complicates
the treatment course. The underlying pathophysiology of worsening renal function
(WRF) involves variable contributions of renal hemodynamics, neurohormonal
activity, and oxidative stress. Historically, WRF has been associated with
adverse outcomes. However, emerging data support therapeutic strategies that
permit WRF while effectively treating congestion as they are associated with
improved outcomes.
PMID- 25135472
TI - Prenatal evaluation and postnatal early outcomes of fetal ventriculomegaly.
AB - OBJECTIVE: This study aims to determine the incidence, etiology, diagnostic
criteria and early outcomes of prenatally diagnosed fetal ventriculomegaly (VM).
METHODS: Diagnostic criteria for the fetal VM was atrial diameter of lateral
ventricle measuring >=10 mm, independent from gestational age. Results of our
patients from ultrasonography (USG), karyotyping, congenital infections, and
associated abnormalities were noted. Progress during pregnancy, postnatal USG
results and neurobehavioral outcomes were recorded. RESULTS: In our study, 40
subjects of fetal VM were recorded. 16 and 24 of those were bilateral (40%) and
unilateral (60%) respectively. Female to male fetus ratio was 19/21 (0.9). Median
gestational age at the diagnosis was 22 weeks (ranging between 16 and 34 weeks).
While 21 VM subjects were isolated (52.5%) only 19 of the total were shown
associated structural abnormalities in (47.5%) in addition to VM. Toxoplasmosis
were diagnosed only in one subject (2.5%). Nineteen subjects had amniocentesis
(47.5%) and 2 of them were showed abnormalities (10.5%) as follows; "inversion
and duplication 8 (p11.2p23)" and "deletion 3". VM got back in to normal size
during pregnancy in 24 subjects (24/40, 60%). Eight pregnancies were terminated
(8/40) (20%). Five babies passed away during neonatal and postneonatal period.
Some other structural abnormalities were diagnosed after the birth at six babies
who classified as mild "isolated" VM. CONCLUSIONS: Our study revealed that
amongst mild VM subjects, incidence of associated abnormalities and termination
rate were higher. Although most of mild VM subjects are thought to be benign,
associated abnormalities should be carefully evaluated and determined pre- and
postnatally.
PMID- 25135473
TI - Evaluation of Gram-negative bacterial infection by a stable and conjugative
bioluminescence plasmid in a mouse model.
AB - BACKGROUND: The green fluorescence protein (GFP)-associated fluorescence method
and the luciferase-associated bioluminescence method are the two major methods
for IVIS imaging system to investigate the bacterial infection in animal models.
The aim of this study was to evaluate the infection route of Gram-negative
bacteria carrying a stable and broad range of conjugative bioluminescence plasmid
pSE-Lux1 in a mouse model. RESULTS: Both encapsulated and non-encapsulated Gram
negative bacteria were used as hosts to evaluate conjugation efficiency and
plasmid stability of pSE-Lux1, a recombinant of pSE34 and luxABCDE operon. The
plasmid conjugation efficiencies of pSE-Lux1 ranged from 10-3 to 10-7 in various
Gram-negative bacteria. Plasmid pSE-Lux1 maintained in Escherichia coli,
Klebsiella pneumoniae, and Salmonella enterica serovars Choleraesues (abbreviated
S. Choleraesuis) and Typhimurium (S. Typhimurium), than in Acinetobacter
baumannii and Serratia marcescens, was shown to be of better stability for at
least four days. To investigate systemic bacterial infections, K. pneumoniae
strain CG354 was intravenously injected, and then was clearly observed to be non
pathogenic to Balb/c mice for a long-term bioluminescence monitoring for 6 days.
For examining dynamic distributions of gastrointestinal tract infection, the
invasion protein SipB-deficient mutant OU5045?sipB and OU5046?sipB of S. serovar
Typhimurium constructed in this study, compared to wild-type strain OU5045 and
its virulence plasmid-less strain OU5046, were of less virulence to mice.
CONCLUSIONS: This is the first study to evaluate the conjugative and stable
bioluminescence vehicle system of pSE-Lux1 in a wide range of Gram-negative
bacteria, a system that can provide a useful reporter approach to trace systemic
and gastrointestinal bacterial infections in a mouse model.
PMID- 25135475
TI - CTCF controls HOXA cluster silencing and mediates PRC2-repressive higher-order
chromatin structure in NT2/D1 cells.
AB - HOX cluster genes are activated sequentially in their positional order along the
chromosome during vertebrate development. This phenomenon, known as temporal
colinearity, depends on transcriptional silencing of 5' HOX genes. Chromatin
looping was recently identified as a conserved feature of silent HOX clusters,
with CCCTC-binding factor (CTCF) binding sites located at the loop bases.
However, the potential contribution of CTCF to HOX cluster silencing and the
underlying mechanism have not been established. Here, we demonstrate that the
HOXA locus is organized by CTCF into chromatin loops and that CTCF depletion
causes significantly enhanced activation of HOXA3 to -A7, -A9 to -A11, and -A13
in response to retinoic acid, with the highest effect observed for HOXA9. Our
subsequent analyses revealed that CTCF facilitates the stabilization of Polycomb
repressive complex 2 (PRC2) and trimethylated lysine 27 of histone H3 (H3K27me3)
at the human HOXA locus. Our results reveal that CTCF functions as a controller
of HOXA cluster silencing and mediates PRC2-repressive higher-order chromatin
structure.
PMID- 25135474
TI - Efficient mRNA polyadenylation requires a ubiquitin-like domain, a zinc knuckle,
and a RING finger domain, all contained in the Mpe1 protein.
AB - Almost all eukaryotic mRNAs must be polyadenylated at their 3' ends to function
in protein synthesis. This modification occurs via a large nuclear complex that
recognizes signal sequences surrounding a poly(A) site on mRNA precursor, cleaves
at that site, and adds a poly(A) tail. While the composition of this complex is
known, the functions of some subunits remain unclear. One of these is a
multidomain protein called Mpe1 in the yeast Saccharomyces cerevisiae and RBBP6
in metazoans. The three conserved domains of Mpe1 are a ubiquitin-like (UBL)
domain, a zinc knuckle, and a RING finger domain characteristic of some ubiquitin
ligases. We show that mRNA 3'-end processing requires all three domains of Mpe1
and that more than one region of Mpe1 is involved in contact with the
cleavage/polyadenylation factor in which Mpe1 resides. Surprisingly, both the
zinc knuckle and the RING finger are needed for RNA-binding activity. Consistent
with a role for Mpe1 in ubiquitination, mutation of Mpe1 decreases the
association of ubiquitin with Pap1, the poly(A) polymerase, and suppressors of
mpe1 mutants are linked to ubiquitin ligases. Furthermore, an inhibitor of
ubiquitin-mediated interactions blocks cleavage, demonstrating for the first time
a direct role for ubiquitination in mRNA 3'-end processing.
PMID- 25135476
TI - Regulation of the death-associated protein kinase 1 expression and autophagy via
ATF6 requires apoptosis signal-regulating kinase 1.
AB - The death-associated protein kinase 1 (DAPK1) is an important regulator of cell
death and autophagy. Recently, we have identified that ATF6, an endoplasmic
reticulum-resident transcription factor, in association with the transcription
factor CEBP-beta, regulates the gamma interferon (IFN-gamma)-induced expression
of Dapk1 (P. Gade et al., Proc. Natl. Acad. Sci. U. S. A. 109:10316-10321, 2012,
doi.org/10.1073/pnas.1119273109). IFN-gamma-induced proteolytic processing of
ATF6 and phosphorylation of C/EBP-beta were essential for the formation of a
novel transcriptional complex that regulates DAPK1. Here, we report that IFN
gamma activates the ASK1-MKK3/MKK6-p38 mitogen-activated protein kinase (MAPK)
pathway for controlling the activity of ATF6. The terminal enzyme in this
pathway, p38 MAPK, phosphorylates a critical threonine residue in ATF6 upstream
of its DNA binding domain. ATF6 mutants defective for p38 MAPK phosphorylation
fail to undergo proteolytic processing in the Golgi apparatus and drive IFN-gamma
induced gene expression and autophagy. We also show that mice lacking Ask1 are
highly susceptible to lethal bacterial infection owing to defective autophagy.
Together, these results identify a novel host defense pathway controlled by IFN
gamma signaling.
PMID- 25135477
TI - FANCD2-controlled chromatin access of the Fanconi-associated nuclease FAN1 is
crucial for the recovery of stalled replication forks.
AB - Fanconi anemia (FA) is a cancer predisposition syndrome characterized by cellular
hypersensitivity to DNA interstrand cross-links (ICLs). Within the FA pathway, an
upstream core complex monoubiquitinates and recruits the FANCD2 protein to ICLs
on chromatin. Ensuing DNA repair involves the Fanconi-associated nuclease 1
(FAN1), which interacts selectively with monoubiquitinated FANCD2 (FANCD2(Ub)) at
ICLs. Importantly, FANCD2 has additional independent functions: it binds
chromatin and coordinates the restart of aphidicolin (APH)-stalled replication
forks in concert with the BLM helicase, while protecting forks from nucleolytic
degradation by MRE11. We identified FAN1 as a new crucial replication fork
recovery factor. FAN1 joins the BLM-FANCD2 complex following APH-mediated fork
stalling in a manner dependent on MRE11 and FANCD2, followed by FAN1 nuclease
mediated fork restart. Surprisingly, APH-induced activation and chromatin
recruitment of FAN1 occur independently of the FA core complex or the FAN1 UBZ
domain, indicating that the FANCD2(Ub) isoform is dispensable for functional
FANCD2-FAN1 cross talk during stalled fork recovery. In the absence of FANCD2,
MRE11 exonuclease-promoted access of FAN1 to stalled forks results in severe FAN1
mediated nucleolytic degradation of nascent DNA strands. Thus, FAN1 nuclease
activity at stalled replication forks requires tight regulation: too little
inhibits fork restart, whereas too much causes fork degradation.
PMID- 25135479
TI - Biotechnological challenges of bioartificial kidney engineering.
AB - With the world-wide increase of patients with renal failure, the development of
functional renal replacement therapies have gained significant interest and novel
technologies are rapidly evolving. Currently used renal replacement therapies
insufficiently remove accumulating waste products, resulting in the uremic
syndrome. A more preferred treatment option is kidney transplantation, but the
shortage of donor organs and the increasing number of patients waiting for a
transplant warrant the development of novel technologies. The bioartificial
kidney (BAK) is such promising biotechnological approach to replace essential
renal functions together with the active secretion of waste products. The
development of the BAK requires a multidisciplinary approach and evolves at the
intersection of regenerative medicine and renal replacement therapy. Here we
provide a concise review embracing a compact historical overview of bioartificial
kidney development and highlighting the current state-of-the-art, including
implementation of living-membranes and the relevance of extracellular matrices.
We focus further on the choice of relevant renal epithelial cell lines versus the
use of stem cells and co-cultures that need to be implemented in a suitable
device. Moreover, the future of the BAK in regenerative nephrology is discussed.
PMID- 25135478
TI - TPC1 has two variant isoforms, and their removal has different effects on endo
lysosomal functions compared to loss of TPC2.
AB - Organelle ion homeostasis within the endo-lysosomal system is critical for
physiological functions. Two-pore channels (TPCs) are cation channels that reside
in endo-lysosomal organelles, and overexpression results in endo-lysosomal
trafficking defects. However, the impact of a lack of TPC expression on endo
lysosomal trafficking is unknown. Here, we characterize Tpcn1 expression in two
transgenic mouse lines (Tpcn1(XG716) and Tpcn1(T159)) and show expression of a
novel evolutionarily conserved Tpcn1B transcript from an alternative promoter,
raising important questions regarding the status of Tpcn1 expression in mice
recently described to be Tpcn1 knockouts. We show that the transgenic Tpcn1(T159)
line lacks expression of both Tpcn1 isoforms in all tissues analyzed. Using mouse
embryonic fibroblasts (MEFs) from Tpcn1(-/-) and Tpcn2(-/-) animals, we show that
a lack of Tpcn1 or Tpcn2 expression has no significant impact on resting endo
lysosomal pH or morphology. However, differential effects in endo-lysosomal
function were observed upon the loss of Tpcn1 or Tpcn2 expression; thus, while
Tpcn1(-/-) MEFs have impaired trafficking of cholera toxin from the plasma
membrane to the Golgi apparatus, Tpcn2(-/-) MEFs show slower kinetics of ligand
induced platelet-derived growth factor receptor beta (PDGFRbeta) degradation,
which is dependent on trafficking to lysosomes. Our findings indicate that TPC1
and TPC2 have important but distinct roles in the endo-lysosomal pathway.
PMID- 25135480
TI - Infrared and Raman spectroscopic investigation of the reaction mechanism of
cytochrome c oxidase.
AB - Recent progress in studies on the proton-pumping and O2reduction mechanisms of
cytochrome c oxidase (CcO) elucidated by infrared (IR) and resonance Raman (rR)
spectroscopy, is reviewed. CcO is the terminal enzyme of the respiratory chain
and its O2reduction reaction is coupled with H+ pumping activity across the inner
mitochondrial membrane. The former is catalyzed by heme a3 and its mechanism has
been determined using a rR technique, while the latter used the protein moiety
and has been investigated with an IR technique. The number of H+ relative to e-
transferred in the reaction is 1:1, and their coupling is presumably performed by
heme a and nearby residues. To perform this function, different parts of the
protein need to cooperate with each other spontaneously and sequentially. It is
the purpose of this article to describe the structural details on the coupling on
the basis of the vibrational spectra of certain specified residues and
chromophores involved in the reaction. Recent developments in time-resolved IR
and Raman technology concomitant with protein manipulation methods have yielded
profound insights into such structural changes. In particular, the new IR
techniques that yielded the breakthrough are reviewed and assessed in detail.
This article is part of a Special Issue entitled: Vibrational spectroscopies and
bioenergetic systems.
PMID- 25135481
TI - Neuromyelitis optica spectrum disorders without and with autoimmune diseases.
AB - BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) can coexist with non
organ-specific or organ-specific autoimmune diseases. The aim of this study was
to investigate and compare the features between NMOSD without and with autoimmune
diseases, and NMOSD with non-organ-specific and organ-specific autoimmune
diseases. METHODS: One hundred and fifty five NMOSD patients without autoimmune
diseases (n = 115) and with autoimmune diseases (n = 40) were enrolled. NMOSD
with autoimmune diseases were divided by organ-specific autoimmune diseases. The
clinical, laboratory and magnetic resonance imaging features between two groups
were assessed. RESULTS: Motor deficit was less frequent in NMOSD patients with
non-organ-specific autoimmune diseases (p = 0.024). Cerebrospinal fluid white
blood cell and protein, serum C-reactive protein and immunoglobulin G were lower
in NMOSD patients without autoimmune diseases, while several autoantibodies
seropositivity and thyroid indexes were significantly higher in NMOSD patients
with autoimmune diseases (p < 0.05). No difference was found in other clinical
and laboratory characteristics between different NMOSD subtypes (p > 0.05). NMOSD
patients with autoimmune diseases had higher brain abnormalities than NMOSD
without autoimmune diseases (p < 0.001). CONCLUSIONS: The characteristics between
NMOSD without and with autoimmune diseases were similar. NMOSD with autoimmune
diseases have high frequency of brain abnormalities.
PMID- 25135482
TI - Hormone whodunit: clues for solving the case of intratumor androgen production.
AB - One of the key mechanisms by which prostate cancer cells evade hormone therapy is
through intratumor testosterone production. New evidence points toward
androstenedione as a potential precursor of intratumor androgen production and
furthers nomination of AKR1C3 as a therapeutic target in advanced disease.
PMID- 25135483
TI - p38 MAPK in pancreatic cancer: finding a protective needle in the haystack.
AB - Activated p38 MAPK alpha (pp38alpha) is a good prognostic marker in pancreatic
ductal adenocarcinoma that could be used to personalize therapy. pp38alpha
suppresses JNK-mediated proliferation, both in vitro and in vivo. These findings
support the testing of combination therapies that include JNK targeting and/or
suppressing negative regulators of pp38alpha.
PMID- 25135484
TI - Matching wits with melanoma brain metastases: from biology to therapeutics.
AB - Melanoma brain metastases (MBM) present a significant clinical challenge.
Molecular profiling of MBM is useful to identify molecular pathways, such as the
PI3K pathway, that are specifically and differentially altered in MBM.
Therapeutic studies should recruit patients with MBM and prospective tissue
collection will lay the foundation for further advances.
PMID- 25135486
TI - Relationship between Na+, K+-ATPase and NMDA receptor at central synapses.
AB - Specific receptors for classical neurotransmitters and neuropeptides, as well as
the Na(+), K(+)-ATPase, are all molecular entities inserted into synaptic region
membranes and localized contiguously. Herein, available experimental evidence
showing close interactions between the activity of the Na(+), K(+)-ATPase and the
N-methyl-D-aspartate (NMDA) ionotropic glutamate receptor was reviewed,
supporting a functional link between these macromolecules. The Na(+), K(+)-
ATPase and NMDA receptor are involved in ion movements through membranes. The
former acts as an ion transporter, whereas the latter acts as an ion channel. The
modulation of their activity plays a critical role in controlling neuronal
function. Examples were taken from studies performed with specific agonists or
antagonists of the NMDA receptor. Regarding the Na(+), K(+)-ATPase, its
involvement was postulated after observing its inhibition by ouabain or related
cardiac glycosides. Additionally, experimental conditions known to prevent normal
Na(+), K(+)-ATPase (i. e., sodium pump functioning) led to similar valuable
information. These findings indicate potential cross-talk between this enzyme and
the NMDA receptor. The Na(+), K(+)-ATPase and NMDA play very important roles in
the regulation of learning and memory in the hippocampus. The fact that important
changes here described were recorded in the hippocampus indicate a different
vulnerability of this area to toxicity induced by the Na(+), K(+)-ATPase
inhibitor ouabain. Some interesting relationships include calcineurin actions,
the participation of ERK or Src family kinases, and signaling cascades initiated
by calcium. At present, many other examples of signaling related to the NMDA
receptor cannot be correlated with Na+, K(+)-ATPase activity. It is desirable
that the development of future research offer new clues for the relationship
between Na(+), K(+)-ATPase and NMDA receptor activation.
PMID- 25135485
TI - Transient extracellular application of gold nanostars increases hippocampal
neuronal activity.
AB - BACKGROUND: With the increased use of nanoparticles in biomedical applications
there is a growing need to understand the effects that nanoparticles may have on
cell function. Identifying these effects and understanding the mechanism through
which nanoparticles interfere with the normal functioning of a cell is necessary
for any therapeutic or diagnostic application. The aim of this study is to
evaluate if gold nanoparticles can affect the normal function of neurons, namely
their activity and coding properties. RESULTS: We synthesized star shaped gold
nanoparticles of 180 nm average size. We applied the nanoparticles to acute mouse
hippocampal slices while recording the action potentials from single neurons in
the CA3 region. Our results show that CA3 hippocampal neurons increase their
firing rate by 17% after the application of gold nanostars. The increase in
excitability lasted for as much as 50 minutes after a transient 5 min application
of the nanoparticles. Further analyses of the action potential shape and
computational modeling suggest that nanoparticles block potassium channels
responsible for the repolarization of the action potentials, thus allowing the
cell to increase its firing rate. CONCLUSIONS: Our results show that gold
nanoparticles can affect the coding properties of neurons by modifying their
excitability.
PMID- 25135489
TI - Staphylococcus aureus toxic shock syndrome toxin-1 (TSST-1) production and
Lactobacillus species growth in a defined medium simulating vaginal secretions.
AB - Lactobacillus species are commensal with the healthy vaginal environment and
inhibit the growth of many pathogenic bacteria in the vaginal tract by a variety
of mechanisms, such as the production of hydrogen peroxide, organic acids, and
antimicrobial substances. Simulation of the vaginal environment is crucial for
proper investigation of the effects of Lactobacillus species on pathogenic
bacteria. In this study, we modified a medium used to simulate vaginal secretions
to improve the growth of toxic shock syndrome toxin-1 (TSST-1)-producing
Staphylococcus aureus clinical strains and Lactobacillus species so that
interactions between these bacteria may be examined. A medium consisting of basal
salts, vitamins, albumin, glycogen, mucin, urea, sodium bicarbonate,
polyoxyethylene sorbitan monolaurate, and amino acids supported the growth of S.
aureus and the production of TSST-1 as determined by Western analysis. Improved
growth of the Lactobacillus species was seen when this same medium was
supplemented with manganese chloride, sodium acetate, and an increase in glucose
concentration. However, growth of S. aureus in the supplemented medium resulted
in reduced levels of TSST-1. Production of TSST-1 was not detected in a medium
routinely used for the growth of Lactobacillus species although S. aureus growth
was not inhibited. The development of an improved genital tract secretion medium
provides a more authentic environment in which to study the interactions of
Lactobacillus species and vaginal pathogens, such as S. aureus.
PMID- 25135488
TI - Rapid 96-well plates DNA extraction and sequencing procedures to identify genome
wide transposon insertion sites in a difficult to lyse bacterium: Lactobacillus
casei.
AB - Random transposon mutagenesis followed by adequate screening methods is an
unavoidable procedure to characterize genetics of bacterial adaptation to
environmental changes. We have recently constructed a mutant library of
Lactobacillus casei and we aimed to fully annotate it. However, we have observed
that, for L. casei which is a difficult to lyse bacterium, methods used to
identify the transposon insertion site in a few mutants (transposon rescue by
restriction and recircularization or PCR-based methods) were not transposable for
a larger number because they are too time-consuming and sometimes not reliable.
Here, we describe a method for large-scale and reliable identification of
transposon insertion sites in a L. casei mutant library of 9250 mutants. DNA
extraction procedure based on silica membranes in 96-column format was optimized
to obtain genomic DNA from a large number of mutants. Then reliable direct
genomic sequencing was improved to fit the obtained genomic DNA extracts. Using
this procedure, readable and identifiable sequences were obtained for 87% of the
L. casei mutants. This method extends the applications of a library of this type,
reduces the number of insertions needed to be screened, and allows selection of
specific mutants from an arrayed and stored mutant library. This method is
applicable to any already existing mutant library (obtained by transposon or
insertional mutagenesis) and could be useful for other bacterial species,
especially for highly lysis-resistant bacteria species such as lactic acid
bacteria.
PMID- 25135487
TI - Efficacy of antibiotic therapy for peritoneal dialysis-associated peritonitis: a
proportional meta-analysis.
AB - BACKGROUND: The choice of antimicrobials for initial treatment of peritoneal
dialysis (PD)-related peritonitis is crucial for a favorable outcome. There is no
consensus about the best therapy; few prospective controlled studies have been
published, and the only published systematic reviews did not report superiority
of any class of antimicrobials. The objective of this review was to analyze the
results of PD peritonitis treatment in adult patients by employing a new
methodology, the proportional meta-analysis. METHODS: A review of the literature
was conducted. There was no language restriction. Studies were obtained from
MEDLINE, EMBASE, and LILACS. The inclusion criteria were: (a) case series and
RCTs with the number of reported patients in each study greater than five, (b)
use of any antibiotic therapy for initial treatment (e.g., cefazolin plus
gentamicin or vancomycin plus gentamicin), for Gram-positive (e.g., vancomycin or
a first generation cephalosporin), or for Gram-negative rods (e.g., gentamicin,
ceftazidime, and fluoroquinolone), (c) patients with PD-related peritonitis, and
(d) studies specifying the rates of resolution. A proportional meta-analysis was
performed on outcomes using a random-effects model, and the pooled resolution
rates were calculated. RESULTS: A total of 64 studies (32 for initial treatment
and negative culture, 28 reporting treatment for Gram-positive rods and 24
reporting treatment for Gram-negative rods) and 21 RCTs met all inclusion
criteria (14 for initial treatment and negative culture, 8 reporting treatment
for Gram-positive rods and 8 reporting treatment for Gram-negative rods). The
pooled resolution rate of ceftazidime plus glycopeptide as initial treatment
(pooled proportion = 86% [95% CI 0.82-0.89]) was significantly higher than first
generation cephalosporin plus aminoglycosides (pooled proportion = 66% [95% CI
0.57-0.75]) and significantly higher than glycopeptides plus aminoglycosides
(pooled proportion = 75% [95% CI 0.69-0.80]. Other comparisons of regimens used
for either initial treatment, treatment for Gram-positive rods or Gram-negative
rods did not show statistically significant differences. CONCLUSION: We showed
that the association of a glycopeptide plus ceftazidime is superior to other
regimens for initial treatment of PD peritonitis. This result should be carefully
analyzed and does not exclude the necessity of monitoring the local microbiologic
profile in each dialysis center to choice the initial therapeutic protocol.
PMID- 25135490
TI - Non-Structural protein 1 (NS1) gene of Canine Parvovirus-2 regresses chemically
induced skin tumors in Wistar rats.
AB - The Non-Structural protein 1 of Canine Parvovirus-2 (CPV2.NS1) plays a major role
in viral cytotoxicity and pathogenicity. CPV2.NS1 has been proven to cause
apoptosis in HeLa cells in vitro in our laboratory. Here we report that CPV2.NS1
has no toxic side effects on healthy cells but regresses skin tumors in Wistar
rats. Histopathological examination of tumor tissue from CPV2.NS1 treated group
revealed infiltration of mononuclear and polymorphonuclear cells with increased
extra cellular matrix, indicating signs of regression. Tumor regression was also
evidenced by significant decrease in mitotic index, AgNOR count and PCNA index,
and increase in TUNEL positive apoptotic cells in CPV2.NS1 treated group.
Further, CPV2.NS1 induced anti-tumor immune response through significant increase
in CD8(+) and NK cell population in CPV2.NS1 treated group. These findings
suggest that CPV2.NS1 can be a possible therapeutic candidate as an alternative
to chemotherapy for the treatment of cancer.
PMID- 25135492
TI - Immunogenicity of recombinant BCGs expressing predicted antigenic epitopes of
bovine viral diarrhea virus E2 gene.
AB - To develop a vaccine to prevent diseases caused by Mycobacterium tuberculosis and
bovine viral diarrhea virus (BVDV) simultaneously, recombinant Bacillus Calmette
Guerin (rBCG) vaccines expressing different regions of the BVDV E2 gene were
constructed. Using DNASTAR 6.0 software, potential antigenic epitopes were
predicted, and six regions were chosen to generate recombinant plasmids with the
pMV361 vector (pMV361-E2-1, pMV361-E2-2, pMV361-E2-3, pMV361-E2-4, pMV361-E2-5
and pMV361-E2-6, respectively). The recombinant plasmids were transformed into
BCG, and protein expression was thermally induced at 45 degrees C. Mice were
immunized with 5 * 10(6) CFU/200 uL of each rBCG strain. Compared with other
groups, BVDV E2 specific antibody titers were higher in mice immunized with rBCG
E2-6. Ratios and numbers of CD4+, CD8+ and IL-12 expressing spleen lymphocytes of
the rBCG-E2-6 group also were higher than those of other groups. Thus, the rBCG
E2-6 vaccine showed the highest immunogenicity of all groups based on the humoral
and cellular responses to vaccination.
PMID- 25135491
TI - Effects of salinomycin and Bacillus subtilis on growth performance and immune
responses in broiler chickens.
AB - The present study was undertaken to compare the effect of salinomycin and
Bacillus subtilis on growth performance, serum antibody levels against
Clostridium spp. and Eimeria spp., and cytokine mRNA expression levels in broiler
chickens raised in the used litter. Broiler chickens fed a diet containing
salinomycin showed lower (P < 0.05) body weights compared with the control diet
fed counterparts. Serum nitric oxide levels were significantly (P < 0.05)
elevated in chickens fed the B. subtilis-enriched diet compared with those on
either the salinomycin-fed or control diet-fed chickens. None of the dietary
treatments affected (P > 0.05) serum antibody levels against Clostridium
perfringens toxins. Both salinomycin and B.subtilis significantly lowered (P <
0.05) the serum levels of Eimeria-specific antibodies compared with the control
group. Salinomycin, but not B. subtilis, significantly modulated (P < 0.05) the
expression of cytokines encoding interferon-gamma (IFN-gamma), interleukin10 (IL
10) and tumor necrosis factor superfamily 15 (TNFSF15) compared with the control
group. In conclusion, dietary salinomycin and B. subtilis affected serum
anticoccidial antibody and intestinal cytokine expression, but failed to improve
growth performance in broiler chickens. Further study is warranted to investigate
the mode of action of salinomycin on host immune response and growth performance
in broiler chickens.
PMID- 25135494
TI - Fusarium oxysporum induces the production of proteins and volatile organic
compounds by Trichoderma harzianum T-E5.
AB - Trichoderma species have been used widely as biocontrol agents for the
suppression of soil-borne pathogens. However, some antagonistic mechanisms of
Trichoderma are not well characterized. In this study, a series of laboratory
experiments were designed to characterize the importance of mycoparasitism,
exoenzymes, and volatile organic compounds (VOCs) by Trichoderma harzianum T-E5
for the control of Fusarium oxysporum f. sp. cucumerinum (FOC). We further tested
whether these mechanisms were inducible and upregulated in presence of FOC. The
results were as follows: T-E5 heavily parasitized FOC by coiling and twisting the
entire mycelium of the pathogen in dual cultures. T-E5 growing medium conditioned
with deactivated FOC (T2) showed more proteins and higher cell wall-degrading
enzyme activities than T1, suggesting that FOC could induce the upregulation of
exoenzymes. The presence of deactivated FOC (T2') also resulted in the
upregulation of VOCs that five and eight different types T-E5-derived VOCs were
identified from T1' and T2', respectively. Further, the excreted VOCs in T2'
showed significantly higher antifungal activities against FOC than T1'. In
conclusion, mycoparasitism of T-E5 against FOC involved mycelium contact and the
production of complex extracellular substances. Together, these data provide
clues to help further clarify the interactions between these fungi.
PMID- 25135495
TI - Infectious diseases in Poland in 2012.
AB - AIM: The aim of the study is to assess the epidemiological situation for
infectious and parasitic diseases in Poland in 2012. MATERIALS AND METHODS: The
main source of data for this study are statistical overviews contained in the
annual bulletins "Infectious Diseases in Poland in 2012" and "Immunizations in
Poland in 2012" (NIPH-NIH, Warsaw 2013) and data contained in the articles
presented in this issue of Przeglad Epidemiologiczny. Information on deaths due
to infectious and parasitic diseases registered in Poland in 2012 and earlier
years is based on the data of the Department for Demographic Research of Central
Statistical Office. RESULTS: Upper respiratory tract infection classified as
"influenza and influenza-like illness" were reported in 2012 in a total number of
1 460 037 cases. In comparison with 2011, it was an 26.2% increase of incidence,
and as compared to the median of 2006-2010 of 286.1%. In 2012, with still the
clear predominance of salmonellosis among intestinal bacterial infections,
downward trend in the incidence of intestinal infections of this etiology
persisted. In 2012 reported number of intestinal infections caused by Salmonella
was, 8 267 (21.5/100 000), which represents incidence decrease of 4.5%. Foodborne
infections of viral etiology were reported in 39462 cases (102.4/100 000). Most
frequent were caused by rotaviruses - 23 692 (61.5/100 000). In 2012, there were
4 684 reported cases of pertussis (12.2/100 000), which means an increased
incidence compared with the previous year by 180%. In 2012, there was an increase
in the number of cases of mumps by 7.5% (from 2 585 to 2 779 cases), and of
rubella by 46.0%, but compared to the median of the years 2006 to 2010 it was a
decrease of 52.9%. In 2012, there was not any case of congenital rubella. Number
of measles cases was 70 (0.18/100 000). In 2012, there was an increase in the
number of cases of invasive disease caused by H. influenzae from 31 in 2011 to 36
in 2012. Number of infections caused by Streptococcus pneumoniae remained in 2012
as compared to 2011, on almost the same level: 436 in 2012 and 430 in 2011.
However, there was a 36% increase in the number of sepsis cases caused by this
organism. The incidence of tuberculosis in total (all forms of TB) in 2012
decreased compared to the previous year from 22.0 to 19.6 /100000, and pulmonary
tuberculosis from 20.5 to 18.2. In 2012, were reported 1 093 cases of HIV
infections (2.84/100 000), compared with the previous year, it was a fall in
incidence of 2.4%. 21 cases of malaria occurred in people, who infection acquired
abroad in malaria endemic areas. In 2012, there were no cases of diphtheria,
poliomyelitis, rabies and viral haemorrhagic fevers outside of dengue, of which 5
cases of infections acquired in endemic areas were reported to National Sanitary
Inspection. Total number of people who died in Poland in 2012 due to infectious
and parasitic diseases, was 2 774. The share of deaths from these causes in the
total number of deaths was 0.72%, and the mortality rate - 7.2/100 000. Out of
all those deaths 41.1% were due to sepsis.
PMID- 25135493
TI - Identification of two dominant linear epitopes on the GP3 protein of highly
pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV).
AB - Glycosylated protein 3 (GP3) of PRRSV is variable between different PRRSV
strains, so it is helpful for subtype classifying by using distinct epitopes. In
this study, two dominant linear GP3 epitopes that were recognized by highly
dilute serum in an enzyme-linked immunosorbent assay (ELISA) were identified.
Sequence alignments of 36 North American (NA) PRRSV isolates revealed that the
epitope H(87)DELGFMV(94) is well conserved, whereas the epitope
T(59)RQAAAEILE(68) differs in other low-virulence NA-type strains, which have at
least one amino acid mutation in this region. A mutational analysis revealed that
none of these mutations could be recognized by the purified antibodies directed
against the corresponding epitope, indicating that the genetic variations altered
the antigenicity of the antigenic region. Using ELISA, we also found that
antibodies directed against the two epitopes were present in more than 45 of 50
HP-PRRS-positive pig sera, suggesting that their antigenicity is excellent in
vivo.
PMID- 25135496
TI - Measles in Poland in 2012.
AB - BACKGROUND: In 1998 Poland, along with all other Member States in the WHO
European Region, implemented Measles Elimination Program coordinated by WHO. It
requires achieving and maintaining very high vaccine coverage (>95%), recording
all cases and suspected cases of measles, and laboratory testing of all suspected
measles cases in the WHO Reference Laboratory. In Poland it is a Laboratory of
Department of Virology, NIPH-NIH. AIM: To assess epidemiological situation of
measles in Poland in 2012, including vaccination coverage in Polish population,
and Measles Elimination Program implementation status. METHODS: The descriptive
analysis was based on data retrieved from routine mandatory surveillance system
and published in the annual bulletins "Infectious diseases and poisonings in
Poland in 2012" and "Vaccinations in Poland in 2012", and measles case-based
reports from 2012 sent to the Department of Epidemiology NIPH-NIH by Sanitary
Epidemiological Stations. RESULTS: In total, there were 70 measles cases
registered in Poland in 2012 (incidence 0.18 per 100 000). The highest incidence
rate was observed among infants (2.08 per 100 000) and children aged 1 year (2.47
per 100 000). In 2012, 37 cases (52,9%) were hospitalized due to measles. No
deaths from measles were reported. Vaccination coverage of children and youth
aged 2-11 years ranged from 83.6% do 99.6% (primary vaccination in children born
in 2011-2006) and from 76.6% do 96.7% (booster dose in children born in 2003
2001). Performance of the surveillance system was insufficient with only 127
measles-compatible cases reported in 2012 (33% of expected reports). Fifty cases
(71%) were confirmed by IgM ELISA test. SUMMARY AND CONCLUSIONS: The
epidemiological situation of measles deteriorated in 2012 in comparison to
proceding year. The results indicate a need to further promote Measles
Elimination Program in Poland, maintain the high immunisation coverage and
improve measles surveillance system.
PMID- 25135498
TI - Rubella in Poland in 2012.
AB - BACKGROUND: In 2004, Poland has adopted the WHO goal of rubella elimination and
congenital rubella syndrome prevention. Participation in the rubella elimination
program requires clinical diagnosis of rubella to be confirmed with laboratory
test. In Poland, until 2003, national vaccination recommendation included a dose
of rubella vaccine only for girls aged 13 years. Among men, the incidence of
measles remained high creating a risk of infection of non-immune pregnant women
which may lead to the development of congenital rubella syndrome in the child.
AIM: To assess epidemiological situation of rubella in Poland in 2012, including
vaccination coverage in Polish population. METHODS: The descriptive analysis was
based on data retrieved from routine mandatory surveillance system and published
in the annual bulletins "Infectious diseases and poisonings in Poland in 2012"
and "Vaccinations in Poland in 2012". RESULTS: In 2012, there was a significant
increase in the number of cases of rubella - 6 263 cases (in 2011, 4 290 cases) -
and the increase in incidence (from 11.1 per 100 thousand. 16.3). The highest
incidence rate, regardless of gender and the environment, was observed among
adolescents aged 15-19 years (118.0 per 100 000). As in 2011, the incidence of
rubella in boys and men was higher than the incidence in girls and women (25.6
versus 7.5). In 2012, no cases of congenital rubella syndrome were registered.
SUMMARY AND CONCLUSIONS: The proportion of laboratory tests confirming/excluding
rubella infection is still very low in Poland. In 2012, only 0.2% of rubella
cases were laboratory confirmed.
PMID- 25135497
TI - Mumps in Poland in 2012.
AB - BACKGROUND: Vaccination against mumps, introduced initially as recommended, from
2003 is mandatory in Poland and given as two dose scheme with MMR vaccine (mumps,
measles, and rubella). Despite observed decline in mumps incidence for over a
decade which is a result of conducted vaccinations, mumps is still a common
childhood disease in Poland. AIM: To assess epidemiological situation of mumps in
Poland in 2012, including vaccination coverage in Polish population, in
comparison to previous years. METHODS: The descriptive analysis was based on data
retrieved from routine mandatory surveillance system and published in the annual
bulletins "Infectious diseases and poisonings in Poland in 2012" and
"Vaccinations in Poland in 2012" (Czarkowski MP i in., Warszawa 2013, NIZP-PZH i
GIS). Mumps cases were classified according to the criteria of surveillance case
definition implemented in the European Union (Commission Decision of 28 April
2008 amending Decision 2002/253/EC). National Immunisation Programme for year
2012 was also used. RESULTS: In total, there were 2779 mumps cases registered in
Poland in 2012. Incidence of mumps was 7.2 per 100 000 and it was higher by 7.5%
in comparison with 2011 and lower by 19.4% in comparison to median for the years
2006-2010. The highest incidence rate was observed among children aged 5 years
(71.8 per 100 000). Incidence in women (5.9) was lower than in men (8.6). In
2012, 25 people were hospitalized due to mumps. Vaccination coverage of children
aged 3 years in Poland in 2012 was 97.9%. CONCLUSIONS: Systematic execution of
mumps vaccination in accordance with the National Immunisation Programme resulted
in a significant decrease in the number of registered cases. Due to the high
vaccination coverage further decline in the number of cases is expected.
PMID- 25135499
TI - Chickenpox in Poland in 2012.
AB - BACKGROUND: A number of chickenpox cases, occurring especially in children,
indicates the rationale for the use of chickenpox vaccinations. In Poland since
2002, chickenpox vaccination is included in the National Immunisation Programme
as recommended. AIM: To assess epidemiological situation of chickenpox in Poland
in 2012 in comparison to previous years. METHODS: The descriptive analysis was
based on data retrieved from routine mandatory surveillance system and published
in the annual bulletins "Infectious diseases and poisonings in Poland in 2012"
and "Vaccinations in Poland in 2012" (Czarkowski MP i in., Warszawa 2013, NIZP
PZH i GIS). National Immunisation Programme for year 2012 was also used. RESULTS:
In 2012, 208 276 cases of chickenpox were registered in Poland. The highest
number of cases was reported in Slaskie voivodeship, the lowest in Podlaskie
voivodeship. Mumps incidence was 540.5 per 100 000 and was higher than in 2011
(448.7). The highest incidence was recorded in children aged 4 years (7 611.5 per
100 000). The chickenpox incidence among men (570.7) was higher than among women
(512.2). The incidence among rural residents (553.9) was higher than among urban
residents (531.8). Number of cases hospitalized due to mumps was 1 361. Number of
people vaccinated against chickenpox was 56 213. SUMMARY: In 2012, there was an
increase in the incidence of smallpox in Poland. This trend is continuing since
2004, which can be partly explained by improved surveillance of the disease.
PMID- 25135500
TI - Pertussis in Poland in 2012.
AB - INTRODUCTION: The epidemiological situation of pertussis in recent years has
changed dramatically. There is a high percentage of cases of pertussis among
adolescents and adults. Infected adults can be a source of infection for non
immune individuals such as infants. The best strategy to prevent illness remains
the implementation of vaccination in accordance with the applicable calendar. THE
AIM OF THE STUDY: To assess the epidemiological situation of pertussis in Poland
in 2012 in comparison to previous years and evaluation of vaccine coverage of
children. MATERIALS AND METHODS: Assessment of the epidemiology of pertussis in
Poland was based on analysis of individual reports of suspected cases of
pertussis sent to the NIPH-NIH by the Regional Sanitary-Epidemiological Stations,
data from the bulletin "Infectious diseases and poisonings in Poland in 2012" and
bulletin "Immunizations in Poland in 2012 "(MP Czarkowski et al., Warsaw 2013,
NIPH-NIH, GIS). RESULTS: In 2012, number of registered cases of whooping cough
was 4 684. The incidence was 12.2 per 100 000 children which was three times as
many as in the previous year (4.3) The majority of cases was among adolescents
aged 10-14 years and above 15 years of age (77%). Number of hospitalized persons
was 1503, (32%) of reported cases. In 2012, there were no deaths from whooping
cough. SUMMARY AND CONCLUSIONS: Observed in 2012, the epidemic increase in the
incidence of pertussis in comparison with previous years, indicates the
circulation of bacteria in the environment and the high sensitivity of the
population to infection.
PMID- 25135501
TI - Scarlet fever in Poland in 2012.
AB - OBJECTIVE: Assessment of the epidemiological situation of scarlet fever in Poland
in 2012. MATERIALS AND METHODS: The evaluation was performed by analysing
surveillance data published in the bulletin, "Infectious diseases and poisonings
in Poland in 2012" (Warsaw 2013, NIPH-NIH, CSI) and also in bulletins from
previous years, and unpublished data collected under Statistical survey program
of official statistics. RESULTS: In the last 15-20 years in Poland has been
observed more than 2-fold lengthening of scarlet fever epidemic cycle, slowdown
in the decline and slower growth rate in epidemic curve and decrease in average
annual incidence. In 2012, in the country a total of 25 421 cases were registered
and incidence was 66.0 per 100 000 population (in voivodeships: from 25.8 in
lodzkie to 114.2 in pomorskie). The highest incidence was notified in 5-year-old
(1094.7) and 6-year-old children (877.3), however, the incidence among children
and young people up to 15 years accounted for 95.6% of all cases. The incidence
of men (74.8) was higher by almost 30% than the incidence of women (57.6). The
incidence was higher in urban areas than in rural areas and was 72.7 (in rural
area 55.7). 0.9% of patients were hospitalized. No deaths related to the disease
were reported. SUMMARY: Distinct changes in the epidemiological situation of
scarlet fever in recent decades are related to, i.a., aging of the Polish
population and decline in the number of children, group particularly vulnerable
to infection. In order to improve accuracy of surveillance data, it is
recommended significantly increase percentage of cases in which clinical
diagnosis will be confirmed by the result of bacteriological examination.
PMID- 25135502
TI - Meningitis and encephalitis in Poland in 2012.
AB - AIM OF THE STUDY: The aim of this study was to assess the epidemiology of
meningitis and/or encephalitis in Poland in 2012. INTRODUCTION: About 2 500-3 000
cases of meningitis and/or encephalitis of viral or bacterial etiology are
recorded in Poland every year. MATERIALS AND METHODS: Assessment of the
epidemiological situation of meningitis and/or encephalitis in Poland in 2012,
was based on the results of analysis of epidemiological reports sent to the NIZP
PZH by the Regional Sanitary-Epidemiological Stations published in the annual
bulletin "Infectious diseases and poisonings in Poland in 2012" and "Preventive
immunizations in Poland in 2012" (Czarkowski MP. et al., Warsaw, 2013, NIZP-PZH,
GIS). RESULTS: In 2012 in Poland 3 088 cases of meningitis and/or encephalitis
were recorded. More than 50% of these were viral infections. SUMMARY AND
CONCLUSIONS: The epidemiological situation of inflammatory meningitis and
encephalitis in Poland in 2012 compared to 2011 did not change significantly.
PMID- 25135503
TI - Legionellosis in Poland in 2012.
AB - OBJECTIVE: The objective of the article is to assess the epidemiological
situation of legionellosis in Poland in 2012 in comparison to the preceding
years. MATERIAL AND METHODS: The analysis of epidemiological situation was based
on the data published in the annual bulletin: "Infectious diseases and poisonings
in Poland in 2012" and its prior versions as well as the legionellosis case
reports sent to the Department of Epidemiology of NIPH-NIH. RESULTS: In Poland,
all cases of legionellosis, including Legionnaires' disease - a form of disease
accompanied by pneumonia and mild, influenza-like form of infection - Pontiac
fever are routinely reported to the surveillance. In 2012, a total of 10
legionellosis cases were reported (8 cases of Legionnaires' disease and 2 cases
of Pontiac fever); the incidence was 0.026 per 100 000 population which compared
to the previous year and median incidence for 2006-2010 was 45% and 65% lower,
respectively. The infections were reported in 6 provinces. The incidence in males
(0.03 per 100 000) was slightly higher compared to females (0.02). No
legionellosis outbreaks were registered - all infections were of sporadic nature.
All cases were hospitalized. The sanitary inspection reported two fatal cases
over the age of 60. Of these infections, seven were developed in the country,
including one hospital- and one sanatorium-acquired infection. Two infections
were associated with travels abroad (one to Spain and one to Egypt) and one
infection occurred in driver while transporting the goods to the Netherlands.
CONCLUSIONS: In 2012, no changes of fundamental features of legionellosis
epidemiological situation in Poland were observed. It is recommended to enhance
the surveillance for legionellosis, with emphasis on conducting environmental
investigation in areas where infections have occurred.
PMID- 25135504
TI - Shigellosis in Poland in 2012.
AB - BACKGROUND: Shigellosis according to European Centre for Disease Control (ECDC)
Report is registered in all countries of the European Union (EU) and of the
European Free Trade Association (EFTA) with exception of Italy and Luxemburg. The
incidence rate in Poland below 0.1/100 000 of population is the lowest among the
EU/EFTA countries. AIM: To assess epidemiological situation of shigellosis in
Poland in 2012 in comparison to preceding years. MATERIALS AND METHODS: An
assessment of the epidemiological situation of shigellosis was based on the
results from an analysis of the yearly annual bulletins: "Infectious diseases and
poisonings in Poland in 2012", reports from bacteriological laboratories and
reports from individual cases and epidemiological investigations of outbreaks
linked to shigellosis, sent by Sanitary-Epidemiological Stations to the
Department of Epidemiology at NIZP-PZH. RESULTS: In 2012 the tendency that the
number of registered cases of shigellosis was lower than in the former years
continued - only 13 confirmed cases of shigellosis were registered (incidence
rate 0.03 per 100 000 inhabitantsbut in the previous year the 18 cases (
incidence rate 0.05). Cases were registered only by 6 provinces, most of the
cases by the Lodz province - 4. All together 5 persons nearly 40% were infected
in travel to the foreign countries. According to data from laboratories of
Sanitary-Epidemiological Stations, Shigella was detected only 4 convalescents and
2 carriers. All cases of shigellosis registered in 2012, were confirmed by a
hospital laboratory or a private laboratory. CONCLUSIONS: In our opinion the
above mentioned data concerning the cases of shigellosis in Poland in 2012 are
not reflecting the true epidemiological situation of shigellosis in Poland. The
sanitary situation was changing nearly every year for better than in former years
but the surveillance of dysentery require more active epidemiological measures.
PMID- 25135505
TI - Foodborne infections and intoxications in Poland in 2012.
AB - AIM: The purpose of the study is to assess the epidemiological situation of
foodborne infections and intoxications in Poland in 2012. MATERIALS AND METHODS:
The evaluation was based on analysis of information from reports of
epidemiological investigations in foodborne outbreaks, submitted by the sanitary
epidemiological stations to the Department of Epidemiology, NIZP-PZH annual
bulletins (Czarkowski MP et al. "Infectious diseases and poisonings in Poland",
2006-2012. Warsaw, NIPH-NIH and CSI). RESULTS: In Poland in 2012 there was
observed decrease in the number of infections intoxications both of bacterial and
viral origin. It was recorded only one case of trichinellosis. There were
reported 491 outbreaks of foodborne poisonings or infections included 5 774
people, among them 718 children 1-14 years old. Out of them 1 364 people were
hospitalized. Unlike last year, the predominant etiological agent in those
outbreaks were zoonotic Salmonella serotypes which caused 38.1% outbreaks and
26.7% outbreak cases. The viruses have caused 27.1% of outbreaks and 36.2% of
cases. In 23.8% of outbreaks etiological agent has not been established. Most
often the settings of an outbreak was a private household - 236 outbreaks and a
hospital (84 outbreaks). As in previous years, the most common vehicle of
infection were foods prepared with milk and eggs -11.8% of outbreaks and egg
dishes - 9.0%. In 57.6% of oubreaks vehicle of infection has not been
established. Among outbreaks reported in 2012, there were 4 which involved more
than 100 people. In 163 outbreaks of food items had been tested and in 33% of
them the results were positive. CONCLUSIONS: The increasing negative results of
bacteriological examinations of food items, suggested necessity to start testing
food contamination with viruses.
PMID- 25135506
TI - Yersiniosis in Poland in 2012.
AB - AIM: The aim of this study is to assess the epidemiology of yersiniosis in Poland
in 2012 compared to previous years. MATERIAL AND METHODS: We reviewed
surveillance data published in the annual bulletin "Infectious diseases and
poisonings in Poland" from 2007 to 2012 (MP Czarkowski et al., NIH and GIS) and
individual yersiniosis case reports from 2012 sent by the Sanitary
Epidemiological Stations. Additionally, we used data from the Department of
Demographic Surveys in Central Statistical Office. RESULTS: In Poland in 2012 a
total of 231 yersiniosis cases were reported including 201 cases of intestinal
and 30 cases of extraintestinal yersiniosis; 61.9% of patients were hospitalized.
The incidence rate was 0.6 per 100 000 inhabitants. No deaths related to the
disease were reported. Intestinal yersiniosis was manifested mostly by following
symptoms: diarrhoea (87%), fever (76%), abdominal pain (47%) and vomiting (31%).
The most affected group in intestinal infections were children younger than 4
years - 145 cases (72% of all cases). Extraintestinal form of infection was more
common than in 2011 (19 cases) and usually involved symptoms from the
osteoarticular system, noted in 90% of patients. Similarly to the previous year
(2011) most cases of yersiniosis were reported from Mazowieckie province (103),
no case has been reported from Swietokrzyskie province. Serological types of
Yersinia enterocolitica were identified in 120 cases (52%): serotype O3 (96.7%),
O8 (2.5%) and O9 (<1%). There were two household outbreaks. In comparison to
previous years the total number of cases caused by serotype O8 has significantly
decreased - from 55 cases in 2011 to 3 cases in 2012. CONCLUSIONS: A large
percentage (48%) of unknown Yersinia serotypes is a consequence, that physicians
do not always request serotyping in routine diagnostics. Reporting cases of
extraintestinal yersiniosis from only few provinces may suggest that the real
number of infections remains underreported.
PMID- 25135507
TI - Campylobacteriosis in Poland in 2012.
AB - AIM: The aim of this paper is to evaluate epidemiological situation of
campylobacteriosis in Poland in 2012, compared to the situation in previous
years. MATERIALS AND METHODS: The evaluation was based on analysis of data from
the annual bulletin "Infectious diseases and poisonings in Poland" 2011-2012 (MP
Czarkowski et al., NIZP-PZH and Chief Sanitary Inspectorate-GIS), information
from the forms of individual cases reports from the epidemiological
investigations in outbreaks of campylobacteriosis, submitted by the sanitary
epidemiological stations to the Department of Epidemiology and data from the
Department of Demographic Studies of the Central Statistical Office. Cases were
classified according to a surveillance case definition. RESULTS: In 2012, 431
cases of campylobacteriosis were registered in Poland, which was 30% more than in
2011. The incidence was 1.12/100 000. All reported cases were classified. No
deaths were recorded. More than 84% of cases of campylobacteriosis occurred in
four provinces - Warminsko-Mazurskie (35%), Slaskie (22%), Mazowieckie (14%) and
the Malopolskie (14%). The highest incidence was observed in the Warminsko
Mazurskie- 6.47/100 000. As in previous years, the percentage of hospitalized
cases was 57.5%. Campylobacter species was identified in more than 77% of
patients, and it was found that 70% of the cases were caused by C. jejuni and
about 7% by C. coli. As in previous years, the majority of cases (343, 79%)
occurred in the age group 0-4. Five family outbreaks caused by Campylobacter were
recorded in 2012. CONCLUSIONS: In Poland Campylobacteriosis is rarely diagnosed,
confirmed and reported. Routine diagnosis of infection with Campylobacter sp. is
performed only in the two provinces.
PMID- 25135508
TI - Salmonellosis in Poland in 2012.
AB - AIM: The purpose of the study was evaluation of epidemiological situation of
salmonellosis in Poland in 2012 compared to the previous years. MATERIALS AND
METHODS: The main source of data for this study are statistical overviews
contained in the annual bulletins "Infectious Diseases in Poland in 2012" (NIZP
PZH, GIS, Warsaw 2013), reports from investigations obtained from the sanitary
epidemiological stations. Information on deaths due to infectious and parasitic
diseases registered in Poland in 2012 and earlier years is based on the data from
the Department for Demographic Research of Central Statistical Office. For the
purpose of surveillance cases were classified according to the case definition.
RESULTS: In Poland in 2012, it was reported a total of 8 444 cases of zoonotic
salmonellosis including 8 267 cases of intestinal salmonellosis and 177 of
extraintestinal one. The incidence was 21.9/100 000. The criteria for a confirmed
case met more than 94% of cases. The number of reported cases was lower than in
2011, reflecting the continued downward trend in the number of cases of
salmonellosis in Poland. A very high percentage (69.4%) hospitalizations of
people infected with zoonotic Salmonella remains. In outbreaks proportion of
hospitalizations accounted for one third of the cases. Predominated children
under the age of 5 years. Seven people died of salmonellosis. In 2012, it was
reported 181 outbreaks caused by Salmonella in which 1 511 people still. They
were mostly small family outbreaks. The most common etiological agent of
salmonellosis in Poland is S. enteritidis, but slightly increases the percentage
cases, for which no serologic type was determined. In 2012 it stood at 14%. This
proportion was highest in the Pomorskie province and amounted to 58%.
CONCLUSIONS: Keeping up for more than 10 years in the percentage of salmonellosis
hospitalization rate at 70%, indicates underreporting of the disease in the
country and mostly detection of the cases requiring hospital treatment. Growing
proportion of Salmonella that are not serotyped, reaching in some regions more
than 30% indicates problems with laboratory diagnostics salmonellosis.
PMID- 25135509
TI - Foodborne botulism in Poland in 2012.
AB - OBJECTIVES: The main objective of this article is to assess the epidemiology of
foodborne botulism in Poland in 2012 compared to previous years, using national
surveillance data. MATERIALS AND METHODS: We reviewed surveillance data published
in the annual bulletin "Infectious diseases and poisonings in Poland in 2012" and
in previous publications, and botulism case reports for 2012 sent to the
Department of Epidemiology NIPH-NIH by Sanitary-Epidemiological Stations.
RESULTS: In 2012, a total of 22 foodborne botulism cases (including 9 laboratory
confirmed cases) was reported, corresponding to the lowest annual incidence rate
(0.06 per 100 000 population) since the introduction of botulism as mandatory
notifiable disease. The highest incidence in the country was reported in
Lubelskie (0.23) and Wielkopolskie (0.20). Incidence in rural areas (0.07 per 100
000 population) was slightly higher than the incidence in urban areas (0.05). Men
had more than 2 times higher incidence than women; the highest incidence rate
(0.20 per 100 000 population) was observed among men in the age group of 30-39
years. Most cases were associated with consumption of different types of
commercially canned meat. Commercially canned fish was also a common vehicle. All
cases were hospitalized. One death related to the disease was reported.
CONCLUSIONS: In 2012, in Poland a downward trend in the incidence of foodborne
botulism was maintained. From the point of view of national surveillance, it is
necessary to increase the percentage of cases investigated with laboratory tests.
PMID- 25135510
TI - Hepatitis A in Poland in 2012.
AB - AIM: The aim of the article is evaluation of the epidemiological situation of
hepatitis A in Poland in 2012. MATERIALS AND METHODS: Assessment of
epidemiological situation of hepatitis A was based on results from analysis of
the annual bulletins: "Infectious diseases and poisonings in Poland in 2012",
"Vaccinations in Poland in 2012", reports from individual cases and
epidemiological investigations of outbreaks linked to hepatitis A, sent by
Epidemiological Departments in Sanitary Epidemiological Stations to the
Department of Epidemiology at NIPH-NIH. RESULTS: In Poland, 71 cases of hepatitis
A were registered in 2012. The incidence of 0.17/ per 100 000 inhabitants was
slightly higher than previous year. The incidence of hepatitis A ranged from
0.08/100 000 in Lodzkie and Podlaskie to 0.35/100 000 in Slaskie. The incidence
of hepatitis A in men and women was at an approximate level and amounted to 0.19
and 0.18/100 000 respectively. The peak of incidence was recorded during the
summer and autumn-winter months. In 2012 imported cases constituted 52.1% of all
cases of hepatitis A. There were five outbreaks involving of 11 registered cases
in 2012. CONCLUSIONS: In 2012, there was a slight increase in the incidence of
hepatitis A in compared with the previous year. However, apart from that there
were no significant changes in the epidemiological situation of hepatitis A. In
Poland there is still very low endemicity for hepatitis A. Decreased incidence
and the small number of people vaccinated against hepatitis A facilitates the
accumulation of a fairly numerous population of persons susceptible to infection
which is connected with the possibility to increase the number of cases of
hepatitis A. Despite the fact that the current epidemiological situation of
hepatitis A in Poland is good, the disease still requires monitoring and analysis
within the framework of epidemiological surveillance system.
PMID- 25135511
TI - Hepatitis B in Poland in 2012.
AB - OBJECTIVES: Evaluation of the epidemiological situation of hepatitis B in Poland
in 2012 in comparison with previous years. MATERIAL AND METHODS: The evaluation
was based on the results of analysis of individual case reports of acute
hepatitis B recorded by the Sanitary-Epidemiological Stations and aggregate data
of national surveillance published in annual bulletins "Infectious diseases and
poisonings in Poland" for the years 2006-2012. RESULTS: In Poland, in 2012 a
total of 1 583 cases of hepatitis B were reported, including 33 cases of
dualinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV). The
incidence was 4.11 per 100 000 inhabitants and compared to the preceding year its
value did not change. The acute cases accounted for 4.9% of all hepatitis B
cases, the incidence - 0.20 per 100 000 population. Compared to 2011, there was a
further decline in both incidence and share of acute stage of infection in the
total number of cases. The highest incidence of acute and chronic form of
hepatitis B was reported in Opolskie (0.49 per 100 000) and Lodzkie provinces
(8.62 per 100 thousand.), respectively. More frequently men and urban dwellers
were ill. In the age group 0-14 years, which was entirely covered by universal
vaccination of infants, no acute cases were found while the incidence of chronic
hepatitis B in this age group was 0.14 per 100 000. Chronic hepatitis B was most
frequently detected in people aged 40-44 years (incidence 7.13 per 100 000) and
acute disease - in those aged 45-49 years (incidence 0.46 per 100 000). Medical
procedures in healthcare settings were still the predominant route of infection
(56% of all acute cases). Infections contracted via sexual contacts, household
contact with an infected person and through injection drug use accounted together
for 14% of all acute hepatitis B cases. In 2012, 11 and 41 persons died due to
acute and chronic stage of hepatitis B, respectively. CONCLUSIONS: A clear
downward trend of the incidence of acute hepatitis B with an unchanged mode of
HBV transmission in Poland, indicates an improvement in compliance with
recommended infection control procedures at all levels of medical care. The
maintenance of the incidence of acute hepatitis B at a low level is possible due
to the continuation of an universal vaccination program against HBV in
combination with measures that stop the spread of infections. In view of
persistent pattern of hepatitis B transmission in Poland in medical settings, it
is advisable to recommend immunization not only to individuals at increased risk
but also all previously unvaccinated persons. Simultaneously, activities leading
to the improvement of detectability and the availability of the recommended
treatment of chronic hepatitis B should be strengthened.
PMID- 25135512
TI - Hepatitis C in Poland in 2012.
AB - INTRODUCTION: In Poland, an estimated 2 000 HCV infections are reported annually,
of which chronic stage of infections predominates (>95%). It is estimated that
seroprevalence of anti-HCV and prevalence of active infections in the general
population amount to ca 0.95% (more than 320 000 persons) and 0.6% (230 000
persons), respectively. The alarming finding is that approximately 90% of persons
diagnosed with HCV infection are unaware of the condition and consequently
hepatitis C virus may be transmitted to their contacts. OBJECTIVE: The objective
of the present article is to determine the epidemiology of HCV infections in
Poland in 2012 comparing to the preceding years. MATERIAL AND METHODS: The
assessment of epidemiological situation of HCV infections in Poland was based on
the analysis of aggregated data from the State Sanitary Inspection, published in
"Infectious diseases and poisonings in Poland in 2012" (Czarkowski MP et al.
"Infectious diseases and poisonings in Poland in 2012" Warsaw, NIPH-NIH and CSI).
The data on mortality due to hepatitis C, which was obtained from the Demographic
Surveys and Labour Market Department of Central Statistical Office, were also
employed. RESULTS: In 2012, Poland reported 2 292 HCV infections, meeting 2005
definition (incidence 5.95), of which 1.4% were co-infections with HCV and HBV
(33 cases). Compared to the data of 2011, the incidence was slightly lower (2
338; 6.07). Given 2009 definition, a total of 2 265 cases were reported (5.88),
which constituted an increase of 3.5% compared to the data from the previous year
(2 241; 5.82). Overall, 217 fatal cases due to hepatitis C were reported in 2012,
of whom only 9 (4%) were due to acute stage of infection. CONCLUSIONS: Compared
to the data from 2011, the epidemiological situation of hepatitis C in Poland has
not changed significantly. The alarming fact is the increasing number of deaths
due to hepatitis C. Probably, it suggests delayed diagnosis of HCV infections.
Thus, it is a necessity to promote early diagnosis of HCV infections which can
prevent life and health-threatening sequelae of hepatitis C.
PMID- 25135513
TI - Tetanus in Poland in 2012.
AB - INTRODUCTION: Despite of the small number of cases reported in Poland tetanus is
a permanent risk to unvaccinated people. The severity of the disease is
associated with high case fatality, especially among people in older age groups.
THE PURPOSE OF THE STUDY: The aim of this paper is to present the data of
epidemiological surveillance of tetanus in 2012. MATERIAL AND METHODS: Principal
source of the data is bulletin: "Infectious diseases and poisonings in Poland in
2012, and individual reports of cases of tetanus sent to the Department of
Epidemiology, NIPH -NIH. RESULTS: In 2012, there were reported 19 cases of
tetanus. 6 cases occurred in men, and 13 women. 13 cases occurred in persons over
69 years of age and in those age groups 6 cases were fatal. The paper describes
the geographical distribution and the month of infection, the nature of the
wounds which were portals of infection and the duration of incubation period of
the cases. SUMMARY AND CONCLUSIONS: Severity of tetanus, despite a small number
of cases each year leads to several deaths, which could be prevented by
vaccination.
PMID- 25135514
TI - Lyme disease in Poland in 2012.
AB - INTRODUCTION: In Poland registration of all cases of Lyme disease is conducted by
the Epidemiological Unit of National Institute of Public Health - National
Institute of Hygiene. Most cases of Lyme disease occur in the North- East region
of Poland; however, it is important to note that the disease is no longer solely
a problem of this region of Poland. OBJECTIVES: The aim of this work is to assess
the epidemiological situation of Lyme disease in Poland in 2012 as compared to
the situation in the previous years. MATERIALS ANDD METHODS: Assessment of the
epidemiological situation of Lyme disease in Poland was made on the basis of an
analysis of individual notifications of suspected Lyme disease submitted to NIZP
NIH by the Provincial Sanitary- Epidemiological Stations; as well as data from
"Infectious diseases and poisoning in Poland in 2012" bulletin, and "Vaccinations
in Poland in 2012" bulletin (MP Czarkowski and Co, Warsaw 2013, NIPH-NIH, NCI).
RESULTS: In 2012 there were 8 782 registered cases of Lyme disease and it is 4.3%
higher than in the previous year. The overall incidence in the country amounted
to 23.8 per 100 000 people. The highest incidence rate was recorded in Podlaskie
province - 75.5 per 100 000 people. 2 063 people were hospitalized due to Lyme
disease. SUMMARY AND CONCLUSIONS: In 2012 incidence rate of Lyme disease was
gradually dropping down. The registered number of cases was reduced by 4.1% in
comparison to the previous year. There is still a fairly low percentage of cases
detected with diagnostic test called Western blot method.
PMID- 25135515
TI - Echinococcosis and cysticercosis in Poland in 2012.
AB - AIM: The aim of the study was to assess the epidemiological situation of
echinococcosis and cysticercosis in 2012 as compared to previous years. MATERIALS
AND METHODS: The assessment of the epidemiological situation was based on data
contained in the individual reports on cases sent to the Department of
Epidemiology NIPH-NIH by the Regional Sanitary- Epidemiological Stations and on
the pooled data published in the annual bulletin "Infectious diseases and
poisonings in Poland". RESULTS: In 2012, the total number of reported cases of
echinococcosis in Poland was 28. This included: 11 undefined cases (39% of all
cases), 7 alveolar echinococcosis cases (41% out of l7 cases in which the species
of Echinococcus was recognized) and 10 cystic echinococcosis (59% of all defined
cases). The total incidence of echinococcosis was 0.073/100 000. Cases were
registered in 8 provinces. Most cases (9) and the highest incidence (0.620) was
recorded in Warminsko-Mazurskie. Echinococcus infections were reported in people
aged 15 to 82 years, mostly adults (mean age 49.2 years, median 54.0).
Echinococcosis was more frequent among women (incidence 0.096) than among men
(incidence 0.048). The incidence of echinococcosis in rural areas was higher than
in the city (0.125 vs. 0.039). Cysticercosis, which occurs sporadically in
Poland, was not reported in 2012. CONCLUSIONS: For the purposes of
epidemiological surveillance it would be advisable to introduce the obligatory
differentiation of alveococcosis and hydatidosis, as well as a case definition
for cysticercosis. In order to reduce the risk of contracting tapeworm
infections, it is advisable to intensify educational efforts.
PMID- 25135516
TI - HIV and AIDS in Poland in 2012.
AB - INTRODUCTION AND AIM: From 1985 until the end of 2013, 17 565 cases of HIV
infection, 3 062 AIDS cases and 1 246 deaths due to AIDS were registered in
Poland. In this paper we aim to analyze the epidemiological situation of newly
diagnosed HIV infections and AIDS cases in Poland in 2012. MATERIALS AND METHODS:
Descriptive analysis of newly detected HIV cases and incident AIDS cases was
performed based on routine notifications by clinicians and laboratories. Data on
the number of HIV tests from annual survey among laboratories were also used.
RESULTS: In 2012 there were 1 093 HIV cases diagnosed in Poland (detection rate
2.84 per 100 000 population), including 27 non-Polish citizens. The detection
rate remained comparable to 2011, but approximately 30% higher than in 2006-2010.
The total number of AIDS cases was 155 (incidence 0.40 per 100 000) and 57 AIDS
patients died (0.15 per 100 000). HIV infection is mainly detected among people
aged 20-39 years (72.6%) and males (83.5%). As many as 70% of newly diagnosed
infections with known route of transmission occurred among men who have sex with
men (MSM). The number of infections in this group increased by 9% from 2011 and
over 3 times compared to 2006-2010 average. The percentage of late presenters
(defined by the time between HIV and AIDS diagnoses of less than 3 months)
decreased in comparison with 2011 (7.9% of newly diagnosed HIV infections).
CONCLUSIONS: HIV epidemic is still spreading among MSM in Poland. However,
assessment of epidemiological situation is limited by the lack of data on the
probable transmission route in a large percentage of reports of newly diagnosed
HIV cases.
PMID- 25135517
TI - Malaria in Poland in 2012.
AB - OBJECTIVE: To describe the epidemiological situation of imported malaria in
Poland in 2012 as compared with previous years. MATERIAL AND METHODS: Evaluation
of malaria epidemiological situation in Poland in 2012, based on the results of
the analysis of individual reports sent to the NIPH-NIH by the Sanitary
Epidemiological Stations and aggregate data published in the annual bulletins
"Infectious Diseases and Poisonings in Poland". Cases were registered according
to the case definition approved in the EU countries. RESULTS: In 2012, a total of
21 malaria cases were registered in Poland, including one fatal case. All cases
were imported from malaria-endemic countries: 52% from Africa and remaining cases
from Asia. Overall, compared to 2011, 7 more cases were reported. Given a median
for the years 2006-2010, the number remained at the same level. In one patient
the recurrence of malaria falciparum was observed following the failure of
treatment undertaken in Cameroon. Plasmodium species was determined in 18 cases
(86%); including 10 (61%) caused by P. falciparum, 6 (33%) by P. vivax and one by
P. malariae. One patient was diagnosed with mixed invasion. Infections were
occurred most frequently during work-related trips (43%) or tourist trips (38%),
in other cases the purpose of the journey was to visit the country of origin
(14%) or its purpose remained unknown. Only four people took any
chemoprophylaxis; in one case, a drug matched inappropriately to the destination
was applied, the remaining three persons applied drugs contrary to the
recommended drug regimen. CONCLUSIONS: The number of cases of imported malaria in
Poland remained at a low level, similar to that observed in previous years. A
large number of delayed diagnoses (more than half of the reported cases) and
another case of fatal outcome in the course of malaria indicate still low
awareness of malaria threat among both travelers and primary care physicians.
PMID- 25135518
TI - Tuberculosis in Poland in 2012.
AB - AIM OF THE STUDY: To evaluate the main features of TB epidemiology in 2012 in
Poland and to compare with the corresponding EU data. METHODS: Analysis of case-
based clinical and demographic data on TB patients from Central TB Register, of
data submitted by laboratories on anti-TB drug susceptibility testing results in
cases notified in 2012, data from National Institute of Public Health - National
Institute of Hygiene on cases of tuberculosis as AIDS-defining disease, from
Central Statistical Office on deaths from tuberculosis based on death
certificates, data from ECDC report "Tuberculosis Surveillance in Europe, 2014
(situation in 2012). RESULTS: 7 542 TB cases were reported in Poland in 2012. The
incidence rate was 19.6 cases per 100 000, with large variability between
voivodships from 10.6 to 30.2. The mean annual decrease of TB incidence in 2008
2012 was 2.4%. 6 665 cases had no history of previous treatment; 17.3 per 100
000. The number of all notified pulmonary tuberculosis cases was 7 018; 18.2 per
100 000. The proportion of extrapulmonary tuberculosis among all registered cases
was 6.9% (524 cases). In 2012, 36 patients had fibrous-cavernous pulmonary
tuberculosis (0.5% of all cases of pulmonary tuberculosis). TB was diagnosed in
95 children (1.3% of all cases, incidence 1.6). The incidence of tuberculosis
increased progressively with age to 34.8 among patients 65 years old and older.
The mean age of new TB cases was 53.1 years. The incidence among men (27.4) was
more than two times higher than among women (12.2). The incidence rate in rural
population was lower than in urban; 20.2 vs. 18.6. Bacteriologically confirmed
pulmonary cases (4870) constituted 69,4% of all pulmonary TB cases. The number of
smear positive pulmonary TB cases was 2 778 (39.6% of all pulmonary cases). In
2012 in the all group of TB patients in Poland there were 276 (3.7%) of homeless
and 1 905 (25.3%) of unemployed. There were 48 foreigners registered among all
cases of tuberculosis in Poland (0.6%) and 243 cases registered among prisoners
(rate 288.0). There were 31 patients with MDR-TB (0.7% of 4659 cases with known
anti-TB DST results). TB was initial AIDS indicative disease in 26 cases. There
were 640 deaths due to tuberculosis in 2011 (1.7 TB deaths per 100 000).
Mortality among males - 2.7 - was four times higher than among females - 0.7.
CONCLUSIONS: CONCLUSIONS. In Poland in 2012 the incidence of tuberculosis was
higher than the average in EU countries. The highest incidence rates occurred in
older age groups. The incidence in men was more than 2 times higher than in
women. The incidence of tuberculosis in children and the percentage of patients
with drug-resistant tuberculosis are lower than average in EU and that is
favorable for epidemiological situation of tuberculosis in our country.
PMID- 25135519
TI - An unusual case of collagenous gastritis in a middle- aged woman with systemic
lupus erythromatosis: a case report.
AB - INTRODUCTION: Collagenous gastritis is a rare histopathologic disease. It is
characterized by marked subepithelial collagen deposition with associated
inflammatory infiltrate. It is considered an uncommon disease among the general
population. Collagenous gastritis without colonic involvement is an extremely
rare disease. It is not known to be associated with systemic lupus
erythromatosis. This is the first report of this type of association. CASE
PRESENTATION: We present a 47-year-old woman from southeast Asia with dyspepsia
and mild anemia. Her past medical history was significant for systemic lupus
erythromatosis, autoimmune hemolytic anemia as well as hypothyroidism. Her
gastroscopy and colonoscopy results were normal from an endoscopic point of view.
However, the histopathology showed collagenous gastritis. CONCLUSIONS: To the
best of our knowledge, this is the first case reported of a patient with systemic
lupus erythromatosis associated with collagenous gastritis. Further studies are
needed to evaluate the association between both diseases from a
pathophysiological and immunological perspective.
PMID- 25135521
TI - Flower opening and closure: an update.
AB - This review is an update of a 2003 review (Journal of Experimental Botany 54,1801
1812) by the same corresponding author. Many examples of flower opening have been
recorded using time-lapse photography, showing its velocity and the required
elongation growth. Ethylene regulates flower opening, together with at least
gibberellins and auxin. Ethylene and gibberellic acid often promote and inhibit,
respectively, the expression of DELLA genes and the stability of DELLA proteins.
DELLA results in growth inhibition. Both hormones also inhibited and promoted,
respectively, the expression of aquaporin genes required for cell elongation.
Arabidopsis miRNA319a mutants exhibited narrow and short petals, whereby
miRNA319a indirectly regulates auxin effects. Flower opening in roses was
controlled by a NAC transcription factor, acting through miRNA164. The regulatory
role of light and temperature, in interaction with the circadian clock, has been
further elucidated. The end of the life span in many flowers is determined by
floral closure. In some species pollination resulted in earlier closure of turgid
flowers, compared with unpollinated flowers. It is hypothesized that this
pollination-induced effect is only found in flowers in which closure is regulated
by ethylene.
PMID- 25135520
TI - A comparative study of ripening among berries of the grape cluster reveals an
altered transcriptional programme and enhanced ripening rate in delayed berries.
AB - Transcriptional studies in relation to fruit ripening generally aim to identify
the transcriptional states associated with physiological ripening stages and the
transcriptional changes between stages within the ripening programme. In non
climacteric fruits such as grape, all ripening-related genes involved in this
programme have not been identified, mainly due to the lack of mutants for
comparative transcriptomic studies. A feature in grape cluster ripening (Vitis
vinifera cv. Pinot noir), where all berries do not initiate the ripening at the
same time, was exploited to study their shifted ripening programmes in parallel.
Berries that showed marked ripening state differences in a veraison-stage cluster
(ripening onset) ultimately reached similar ripeness states toward maturity,
indicating the flexibility of the ripening programme. The expression variance
between these veraison-stage berry classes, where 11% of the genes were found to
be differentially expressed, was reduced significantly toward maturity, resulting
in the synchronization of their transcriptional states. Defined quantitative
expression changes (transcriptional distances) not only existed between the
veraison transitional stages, but also between the veraison to maturity stages,
regardless of the berry class. It was observed that lagging berries complete
their transcriptional programme in a shorter time through altered gene
expressions and ripening-related hormone dynamics, and enhance the rate of
physiological ripening progression. Finally, the reduction in expression variance
of genes can identify new genes directly associated with ripening and also assess
the relevance of gene activity to the phase of the ripening programme.
PMID- 25135522
TI - Microtubule array reorientation in response to hormones does not involve changes
in microtubule nucleation modes at the periclinal cell surface.
AB - Aligned microtubule arrays spatially organize cell division, trafficking, and
determine the direction of cell expansion in plant cells. In response to changes
in environmental and developmental signals, cells reorganize their microtubule
arrays into new configurations. Here, we tested the role of microtubule
nucleation during hormone-induced microtubule array reorientation. We have found
that in the process of microtubule array reorientation the ratios between
branching, parallel, and de-novo nucleations remained constant, suggesting that
the microtubule reorientation mechanism does not involve changes in nucleation
modes. In the ton2/fass mutant, which has reduced microtubule branching
nucleation frequency and decreased nucleation activity of the gamma-tubulin
complexes, microtubule arrays were able to reorient. Presented data suggest that
reorientation of microtubules into transverse arrays in response to hormones does
not involve changes in microtubule nucleation at the periclinal cell surface.
PMID- 25135524
TI - The effect of duty hour regulation on resident surgical case volume in
otolaryngology.
AB - OBJECTIVE: Evaluate the effect of duty hour regulation on graduating
otolaryngology resident surgical case volume and analyze trends in surgical case
volume for Accreditation Council for Graduate Medical Education (ACGME) key
indicator cases from 1996 to 2011. STUDY DESIGN: Time-trend analysis of surgical
case volume. SETTING: Nationwide sample of otolaryngology residency programs.
SUBJECTS: Operative logs from the American Board of Otolaryngology and ACGME for
otolaryngology residents graduating in the years 1996 to 2011. METHODS: Key
indicator volumes and grouped domain volumes before and after resident duty hour
regulations (2003) were calculated and compared. Independent t test was performed
to evaluate overall difference in operative volume. Wilcoxon rank sum test
evaluated differences between procedures per time period. Linear regression
evaluated trend. RESULTS: The average total number of key indicator cases per
graduating resident was 440.8 in 1996-2003 compared to 500.4 cases in 2004-2011,
and overall average per number of key indicators was 31.5 and 36.2, respectively
(P = .067). Four key indicator cases showed statistically significant (P < .05)
increases in volume after duty hour implementation. General/pediatrics was the
only grouped domain to show a significant increase. In contrast, the rate of
change in operative volume decreased post duty hour for only 2 key indicators (P
< .05). The year-by-year trend in average operative volume showed significant
increases for 5 key indicator cases (P < .05). CONCLUSION: Implementation of the
2003 duty hour regulations has not reduced total volume of key indicator cases
for graduating otolaryngology residents. The overall trend in operative volume is
increasing for several specific key indicators.
PMID- 25135523
TI - In vivo tmRNA protection by SmpB and pre-ribosome binding conformation in
solution.
AB - TmRNA is an abundant RNA in bacteria with tRNA and mRNA features. It is
specialized in trans-translation, a translation rescuing system. We demonstrate
that its partner protein SmpB binds the tRNA-like region (TLD) in vivo and
chaperones the fold of the TLD-H2 region. We use an original approach combining
the observation of tmRNA degradation pathways in a heterologous system, the
analysis of the tmRNA digests by MS and NMR, and co-overproduction assays of
tmRNA and SmpB. We study the conformation in solution of tmRNA alone or in
complex with one SmpB before ribosome binding using SAXS. Our data show that
Mg(2+) drives compaction of the RNA structure and that, in the absence of Mg(2+),
SmpB has a similar effect albeit to a lesser extent. Our results show that tmRNA
is intrinsically structured in solution with identical topology to that observed
on complexes on ribosomes which should facilitate its subsequent recruitment by
the 70S ribosome, free or preloaded with one SmpB molecule.
PMID- 25135526
TI - Placement of an internal-external biliary drain through a bilio-enteric fistula
in a neonate to re-establish antegrade bile flow after liver transplantation.
AB - Three-month-old baby girl with history of post-liver transplant hepatic artery
dissection treated with ligation after take down of the biliary anastomosis and
placement of a surgical external common bile duct drain. There was persistent
malfunction of this drain. A bilio-enteric fistula was noted during the later
placement of an image guided percutaneous external drain. Subsequently, an
internal-external biliary drain was successfully placed through this fistula. An
excellent clinical and functional result was achieved.
PMID- 25135528
TI - A personal journal journey.
PMID- 25135525
TI - Head and neck sarcomas: analysis of the SEER database.
AB - OBJECTIVE: To summarize the epidemiology of sarcomas occurring in the head and
neck and identify prognostic factors for patient survival. STUDY DESIGN AND
SETTING: Cross-sectional analysis of the National Cancer Institute's
Surveillance, Epidemiology and End Results (SEER) program. METHODS: The SEER 18
registries, comprising sarcoma diagnoses made from 1973 to 2010, were queried for
sarcomas arising in the head and neck. Pediatric and adult patients were analyzed
separately, and multivariate and propensity-matched analyses were performed to
identify predictors of disease-specific survival. RESULTS: In all, 11,481 adult
cases and 1244 pediatric cases were identified. In adults, the most common
histologic subtypes were malignant fibrous histiocytoma (MFH), Kaposi sarcoma,
and hemangiosarcoma, while in the pediatric cohort, the most common histologic
subtypes were rhabdomyosarcoma, MFH, and osteosarcoma. Cause-specific 2-, 5-, and
10-year survival rates were 76%, 66%, and 61% for adults and 84%, 73%, and 71%
for pediatric patients. Multivariate analysis performed for adults revealed that
male gender, absence of radiation therapy, and stage I disease were associated
with improved cause-specific survival reaching statistical significance. However,
a propensity-matched model demonstrated no significant difference in cause
specific survival between patients who received radiation and those who did not.
CONCLUSION: Sarcomas, a heterogeneous group of malignant mesenchymal tumors, are
uncommonly found in the head and neck. This study represents the largest analysis
of patients with head and neck sarcomas in the literature and demonstrates the
impact of age, gender, primary site, histology, and radiation status on overall
prognosis.
PMID- 25135527
TI - Refractive corneal lenticule extraction.
PMID- 25135529
TI - Intraocular lens scaffold to facilitate intraocular lens exchange.
AB - We describe a technique of intraocular lens (IOL) exchange in patients with post
refractive surgery IOL power error or patients who are dissatisfied with the
optical performance of the IOL. The technique involves the presence of 2 IOLs in
the eye: the offending IOL, which is manipulated out of the capsular bag into the
anterior chamber, and the corrective IOL, which is inserted into the bag. The
anteriorly elevated IOL is transected with the IOL cutting scissors, while the
corrective IOL acts as a scaffold for the posterior capsule. The technique
provides continuous distension of the bag with the IOL, which prevents damage to
the posterior capsule and acts as a barrier to vitreous prolapse in cases of an
open posterior capsule; it also prevents slippage of the optic during transection
of the IOL being removed. FINANCIAL DISCLOSURE: No author has a financial or
proprietary interest in any material or method mentioned.
PMID- 25135530
TI - Phacoemulsification using 8 flexible iris hooks in a patient with a short eye,
small pupil, and phacodonesis.
AB - We describe a technique that uses flexible iris hooks to dilate and stabilize the
capsular bag in a patient with a very deep set and small eye, narrow palpebral
fissure, shallow anterior chamber, and very small pupil, who was scheduled for
routine phacoemulsification for a white cataract. At the time of iris hook
placement, the capsular bag was noted to be markedly unstable. The patient was
managed successfully with phacoemulsification of the lens using 4 iris hooks to
dilate the pupil and 4 iris hooks to stabilize the capsular bag during surgery. A
foldable posterior chamber 3-piece intraocular lens was fixated in the ciliary
sulcus. FINANCIAL DISCLOSURE: Neither author has a financial or proprietary
interest in any material or method mentioned.
PMID- 25135531
TI - Closure technique for leaking wound resulting from thermal injury during
phacoemulsification.
AB - We describe a method of wound closure with a conjunctival flap in cases of wound
burn. A fornix-based conjunctival flap is raised to adequately cover the wound.
Then, a single horizontal mattress suture with 10-0 monofilament nylon is passed
to appose the wound. The conjunctival flap is hinged to the corneal end of the
loop so the conjunctival flap covers the wound when the suture is tied. The wound
is thus sealed by conjunctiva with optimum suture tension. This suture was
applied in 5 patients with clear corneal incisions who developed wound burn
during phacoemulsification. All had an uneventful recovery with a sealed wound
from the first postoperative day and satisfactory visual outcomes with low
residual astigmatism at the final refraction. FINANCIAL DISCLOSURE: Neither
author has a financial or proprietary interest in any material or method
mentioned.
PMID- 25135532
TI - Refractive lenticule extraction: transition and comparison of 3 surgical
techniques.
AB - PURPOSE: To describe the transition and outcomes of 3 refractive lenticule
extraction (ReLEx) techniques: femtosecond lenticule extraction (FLEx), small
incision lenticule extraction (SMILE), and pseudo small-incision lenticule
extraction. SETTING: Singapore National Eye Center, Singapore. DESIGN:
Prospective comparative case series. METHODS: Refractive lenticule extraction was
performed between March 1, 2010, and November 1, 2012, using the Visumax 500 kHz
femtosecond laser system. The main outcome measures were the refractive efficacy,
predictability, and safety over 12 months. RESULTS: The study enrolled 88 eyes.
All 3 refractive lenticule extraction techniques yielded good refractive outcomes
and stability over 12 months. Three months postoperatively, the mean overall
efficacy index of refractive lenticule extraction was 0.89+/-0.22 (SD), with
95.5% of eyes attaining an uncorrected distance visual acuity (UDVA) of better
than 20/40 and 60.2% of better than 20/20. Of all eyes, 95.5% were within +/-1.00
diopter (D) and 78.4% within +/-0.50 D of the attempted correction. The mean
overall safety index was 1.06+/-0.17. At 3 months, all small-incision lenticule
extraction eyes and 96.7% of pseudo small-incision lenticule extraction eyes had
a UDVA of 20/40 or better, while femtosecond lenticule extraction eyes had a
lower efficacy index (87.0%). However, efficacy was comparable in all 3 groups by
12 months (mean 0.87+/-0.04 [standard error of the mean]; P=1.00). CONCLUSION:
The efficacy, safety, and predictability profiles of the 3 refractive lenticule
extraction techniques were good over a 12-month follow-up. FINANCIAL DISCLOSURE:
No author has a financial or proprietary interest in any material or method
mentioned.
PMID- 25135533
TI - Five-year results of refractive lenticule extraction.
AB - PURPOSE: To evaluate the 5-year results of femtosecond laser-assisted refractive
lenticule extraction (ReLEx-FLEx) for the treatment of myopia and myopic
astigmatism. SETTING: Departments of Ophthalmology, Helios Klinikum Erfurt,
Erfurt, and Phillips Universitat Marburg, Marburg, Germany. DESIGN: Prospective
clinical trial. METHODS: This was a follow-up of a prospective study that
evaluated the first patients treated with refractive lenticule extraction, in
which a flap and a refractive lenticule of intrastromal corneal tissue were
simultaneously cut using a 200 kHz Visumax femtosecond laser system. Thereafter,
the lenticule was manually removed and the flap repositioned. The main outcome
measures were the uncorrected and corrected distance visual acuities, objective
and manifest refractions, slitlamp examination findings, and side effects after 5
years. RESULTS: Forty-one of 108 eyes in the original treatment group were
available for a reexamination. Five years postoperatively, 100% of eyes were
within +/-1.00 diopter (D) of the intended correction and 73% were within +/-0.50
D. By 5 years, no eye had lost 2 or more Snellen lines and 1 eye had lost 1
Snellen line. The mean regression was 0.07 D. CONCLUSION: Long-term data indicate
that refractive lenticule extraction is an effective and safe procedure for the
treatment of myopia and myopic astigmatism and has excellent stability. FINANCIAL
DISCLOSURE: No author has a financial or proprietary interest in any material or
method mentioned.
PMID- 25135534
TI - Simultaneous topography-guided partial photorefractive keratectomy and corneal
collagen crosslinking for keratoconus.
AB - PURPOSE: To report the visual, refractive, and clinical outcomes of simultaneous
topography-guided partial photorefractive keratectomy (PRK) and corneal collagen
crosslinking (CXL) in eyes with keratoconus. SETTING: Private practice surgery
center, Dubai, United Arab Emirates. DESIGN: Retrospective cohort study. METHODS:
Refraction, uncorrected (UDVA) and corrected (CDVA) distance visual acuities,
flat and steep keratometry (K) readings, and complications were evaluated 1, 3,
6, and 12 months postoperatively. RESULTS: The study enrolled 31 eyes of 31
patients aged 21 to 42 years. All study parameters showed a statistically
significant improvement at 3, 6, and 12 months over baseline values. At 12
months, the mean UDVA improved to 0.23 logMAR+/-0.33 (SD) from 0.79+/-0.36 logMAR
(P<.001) and the CDVA improved to 0.06+/-0.07 logMAR from 0.28+/-0.20 logMAR
(P<.001). The mean defocus decreased from 3.45+/-1.60 diopters (D) to 1.88+/-1.58
D (P<.001). The flat K and steep K readings showed significant flattening. The
mean refractive astigmatism decreased from -2.77+/-1.47 D to -0.98+/-0.76 D
(P<.001). The improvement in study parameters plateaued after 3 months.
CONCLUSION: Simultaneous topography-guided partial PRK and CXL was effective,
safe, and stable in keratoconus patients. FINANCIAL DISCLOSURE: No author has a
financial or proprietary interest in any material or method mentioned.
PMID- 25135535
TI - Long-term results of combined transepithelial phototherapeutic keratectomy and
corneal collagen crosslinking for keratoconus: Cretan protocol.
AB - PURPOSE: To present the long-term results of combined transepithelial
phototherapeutic keratectomy (PTK) and corneal collagen crosslinking (CXL) for
keratoconus. SETTING: Vardinoyiannion Eye Institute of Crete, University of
Crete, Heraklion, Crete, Greece. DESIGN: Prospective case series. METHODS:
Patients with progressive keratoconus had combined transepithelial PTK and CXL
(Cretan protocol). Visual and refractive outcomes and the endothelial cell
density (ECD) were evaluated preoperatively and postoperatively. RESULTS: Twenty
patients (23 eyes) were enrolled; postoperatively 23 eyes were evaluated at 1 and
2 years, 11 at 3 years, and 7 at 4 years. The mean follow-up was 33.83 months+/
10.82 (SD) (range 24 to 56 months). No intraoperative or postoperative
complications occurred. The mean uncorrected distance visual acuity improved
significantly from 0.99+/-0.57 logMAR preoperatively to 0.61+/-0.36 logMAR at the
last follow-up (P<.001) and the mean corrected distance visual acuity, from
0.27+/-0.24 logMAR to 0.17+/-0.14 logMAR (P=.018), respectively. The mean steep
and mean flat keratometry readings decreased significantly from 53.39+/-7.14
diopters (D) and 47.17+/-4.87 D, respectively, preoperatively to 49.99+/-4.36 D
(P<.001) and 45.47+/-2.95 D (P=.002), respectively, at the last follow-up. The
mean corneal astigmatism improved significantly from -6.27+/-4.19 D
preoperatively to -4.52+/-2.80 D (P<.001) at the last follow-up. No significant
ECD alterations occurred (P>.05). CONCLUSION: Combined transepithelial PTK and
CXL was effective and safe in keratoconic patients over a long-term follow-up.
FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any
material or method mentioned.
PMID- 25135536
TI - Corneal resistance factor and corneal hysteresis in a 6- to 18-year-old
population.
AB - PURPOSE: To determine the distribution and normal range of the corneal resistance
factor (CRF) and corneal hysteresis (CH) in the 6- to 18-year age range and their
relationship with biometric components. SETTING: Dezful, Iran. DESIGN: Cross
sectional study. METHODS: This study of Dezful school children used a multistage,
stratified, cluster approach sampling. All students had examinations for
biometry, noncycloplegic refraction, and corneal biomechanical properties; the
examinations were performed in the same order in all cases. RESULTS: Of the 864
selected students, 683 participated in the study. The mean CRF and CH was 11.74
mm Hg+/-1.77 (SD) (95% confidence interval [CI], 11.58-11.89) and 11.49+/-1.91 mm
Hg (95% CI, 11.33-11.65), respectively. In a linear multiple regression model,
the CRF significantly correlated with female sex (beta coefficient=0.488,
P=.013), central corneal thickness (CCT) (beta coefficient=.034, P=.001), and
keratometry (beta-coefficient=0.157, P=.003) and CH significantly correlated with
CCT (beta coefficient=0.025, P<.001), axial length (beta coefficient=-0.303,
P=.011), and keratometry (beta coefficient=0.11, P=.043). Each year increase in
age was associated with a 42-unit decrease in the peak 1 area (P=.003).
CONCLUSIONS: The distribution of CRF and CH in an Iranian population was
symmetrical and bell shaped. However, the CRF did not have a normal distribution.
The mean CRF and CH were higher than those reported in almost all previous
studies. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest
in any material or method mentioned.
PMID- 25135537
TI - Long-term ultrasound biomicroscopy observation of position changes of a copolymer
posterior chamber phakic intraocular lens.
AB - PURPOSE: To evaluate longitudinal changes in Implantable Collamer Lens phakic
intraocular lens (pIOL) position after implantation. SETTING: Department of
Ophthalmology, Zhejiang University, Hangzhou, China. DESIGN: Retrospective case
series. METHODS: Myopic eyes that had pIOL implantation with a follow-up of at
least 24 months were evaluated. Ultrasound biomicroscopy examinations were
performed at each visit. RESULTS: The study enrolled 62 eyes (31 patients; 22
women, 9 men) ranging in age from 21 to 46 years. The manifest spherical
equivalent ranged from -8.25 to -18.75 diopters. A significant increase (mean 36
MUm+/-50 [SD]) in the endothelium-anterior pIOL distance occurred between 1 month
and 3 months (P=.000); afterward, the distance decreased slowly (P>.05). The
largest decrease (mean 47+/-17 MUm) in central vault occurred between 1 month and
3 months (P=.009). The largest decrease (mean 21+/-14 MUm) in peripheral vault
occurred between 1 month and 3 months (P=.000). CONCLUSIONS: A significant
increase in the endothelium-anterior pIOL distance occurred from 1 month to 3
months postoperatively, after which a slight decrease occurred over time. Central
vault and peripheral vault had a tendency to decrease over time. FINANCIAL
DISCLOSURE: No author has a financial or proprietary interest in any material or
method mentioned.
PMID- 25135538
TI - Evaluation of an electronic reading desk to measure reading acuity in
pseudophakic patients.
AB - PURPOSE: To compare a new electronic reading desk (Salzburg-Advanced) with
conventional measurements of reading acuity. SETTING: Vienna Institute for
Research in Ocular Surgery, Hanusch Hospital, Vienna, Austria. DESIGN: Evaluation
of diagnostic test. METHODS: In study 1, the electronic reading desk was compared
with the same version of a printed reading chart. All patients were measured
twice with autorefraction (Topcon KR8800) and subjective refraction. In study 2,
patients were measured once. In addition, electronic reading desk measurements
were obtained under different contrast and luminance levels. RESULTS: Study 1
evaluated 100 eyes of 50 pseudophakic patients. Differences between the
electronic reading desk and the printed version were small and not significant
for reading speed (131.1 words per minute [wpm]+/-28.7 [SD] versus 134.9+/-20.7
wpm), reading distance (44.7+/-14.4 cm versus 39.6+/-7.6 cm), and smallest
possible read print size (1.95+/-0.58 mm versus 2.02+/-0.70 mm), respectively.
Study 2 evaluated 40 eyes of 20 pseudophakic patients. Reading acuity and the
smallest possible read print size decreased with lower contrast and reduced
luminance, whereas reading distance and reading speed did not change
significantly. CONCLUSIONS: Measurements performed with the electronic reading
desk can be used interchangeably with those performed using a printed chart. The
opportunity to preset standardized luminance and contrast settings could be
useful for measurements in clinical trials. FINANCIAL DISCLOSURES: Drs. Dexl and
Grabner have a proprietary interest in the Salzburg Reading Desk technology as
patent assignees. No other author has a financial or proprietary interest in any
material or method mentioned.
PMID- 25135539
TI - Influence of intraocular lens haptic design on refractive error.
AB - PURPOSE: To assess the influence of intraocular (IOL) haptic design on the
refraction prediction error in patients having cataract surgery. SETTING: Private
practice. DESIGN: Comparative case series. METHODS: Corneal power and axial
length were measured with the same devices in eyes with a 3-piece Acrysof IOL and
eyes with a 1-piece Acrysof IOL and were entered into the Haigis, Hoffer Q,
Holladay 1, and SRK/T formulas. The median absolute error and mean absolute error
in refraction prediction (ie, difference between expected refraction and actual
refraction) were assessed 1 month postoperatively. RESULTS: The study evaluated
110 eyes with the 3-piece IOL and 84 eyes with the 1-piece IOL. With all
formulas, the median absolute error was lower with the 3-piece IOL. It ranged
between 0.15 diopter (D) (Haigis and Holladay 1) and 0.19 D (SRK/T) with the 3
piece IOL and between 0.23 D (Haigis) and 0.30 D (SRK/T) with the 1-piece IOL.
With all formulas, a higher percentage of eyes with the 3-piece IOL were within
+/-0.25 D and +/-0.50 D of the target refraction. CONCLUSIONS: Three-piece IOLs
may yield better refractive outcomes than 1-piece IOLs. A possible reason is that
once the early forward IOL shift previously observed with the 3-piece design
occurs because of the haptic-compression force decay typical of these IOLs, the
rigid haptics of 3-piece IOLs still exert more pressure against the capsular bag
than the haptics of 1-piece IOLs. Therefore, 3-piece IOLs may better resist
subsequent capsule contraction and provide a more predictable effective lens
position. FINANCIAL DISCLOSURE: Dr. Hoffer receives royalties for his book IOL
Power, Slack, Inc., and formula royalties from all manufacturers using the Hoffer
Q formula. No other author has a financial or proprietary interest in any
material or method mentioned.
PMID- 25135540
TI - Clinical outcomes and rotational stability of a 4-haptic toric intraocular lens
in myopic eyes.
AB - PURPOSE: To evaluate the refractive outcomes and rotational stability of a 4
haptic toric intraocular lens (IOL) in myopic eyes and the correlations between
IOL rotation and refractive sphere, axial length (AL), and white-to-white (WTW)
diameter. SETTING: Eye Clinic, Careggi Hospital, Florence, Italy. DESIGN:
Prospective case series. METHODS: Phacoemulsification cataract extraction and
implantation of an AT Torbi 709M IOL were performed. Corneal astigmatism was 1.50
diopters (D) or greater and the AL between 25.0 mm and 27.0 mm in all eyes. The
uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refraction, and
IOL axis were evaluated preoperatively and postoperatively up to 6 months.
RESULTS: The study enrolled 20 eyes (20 patients). The UDVA and CDVA improved
significantly postoperatively (P<.001). The mean refractive spherical equivalent
decreased significantly from -7.10 D+/-1.78 (SD) preoperatively to -0.55+/-0.25 D
1 day postoperatively (P<.001) and remained stable thereafter. Vector analysis
showed that 90% and 85% of the eyes were within +/-0.25 D for J0 and J45,
respectively. At 3 months and 6 months, the mean IOL rotation was 2.66+/-1.53
degrees and 3.00+/-1.69 degrees, respectively (P<.001), with 95% of eyes and 90%
of eyes, respectively, within +/-5 degrees. A positive correlation was found
between IOL rotation and preoperative sphere; none was found with AL and WTW.
CONCLUSIONS: Implantation of the 4-haptic toric IOL in myopic eyes was effective
and safe. The IOL showed no significant rotation over the 6-month follow-up.
FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any
material or method mentioned.
PMID- 25135541
TI - Pars plana vitrectomy combined with iris-claw intraocular lens implantation for
lens nucleus and intraocular lens dislocation.
AB - PURPOSE: To assess the medium-term efficacy and safety of treating nucleus and
intraocular lens (IOL) dislocation with pars plana vitrectomy (PPV) combined with
iris-claw IOL implantation. SETTING: Department of Ophthalmology, University of
Lyon 1 Claude Bernard, Lyon, France. DESIGN: Retrospective case series. METHODS:
The study comprised consecutive patients without capsule support having PPV
combined with iris-claw IOL implantation for posterior dislocation of the nucleus
or IOL between 2008 and 2012. The preoperative, intraoperative, and postoperative
data were retrospectively analyzed. Patients were invited to a prospective final
examination at least 6 months postoperatively. RESULTS: The study enrolled 32
eyes (31 consecutive patients). The dislocation was spontaneous in 8 cases and
traumatic in 24 (intraoperative 17 cases, contusive 7 cases). The iris-claw IOL
was on the anterior side of the iris in 19 cases and on the posterior side in 13
cases. The mean corrected distance visual acuity at the end of follow-up was
20/40 or better in 22 patients (69%). The mean spherical equivalent was +8.20
(SD)+/-6.03 diopters (D) preoperatively and -0.51+/-1.14 D postoperatively. The
median endothelial cell loss was 20.5% over the first 3 months. The complications
were cystoid macular edema (n=8), retinal detachment (n=4), transient
intravitreal hemorrhage (n=4), secondary glaucoma (n=2), and choroidal detachment
(n=1). The final examination was performed in 27 eyes. CONCLUSION: Treatment of
nucleus and IOL dislocation with PPV combined with iris-claw IOL implantation was
effective and safe over the medium-term. FINANCIAL DISCLOSURE: No author has a
financial or proprietary interest in any material or method mentioned.
PMID- 25135542
TI - Nepafenac 0.1% plus dexamethasone 0.1% versus dexamethasone alone: effect on
macular swelling after cataract surgery.
AB - PURPOSE: To evaluate the efficacy of adding nepafenac 0.1% ophthalmic suspension
to dexamethasone 0.1% eyedrops in controlling macular swelling and other
manifestations of inflammation after uneventful cataract surgery. SETTING:
Ophthalmology Department, Molndal Hospital, Gothenburg, and St. Erik Eye
Hospital, Stockholm, Sweden. DESIGN: Randomized double-masked clinical trial.
METHODS: Patients at low risk for postoperative inflammation were recruited and
randomized to the nepafenac group or to the control group. Postoperative swelling
of the macula was assessed with ocular coherence tomography. Laser flare
intensity, corrected distance visual acuity, ocular discomfort, and visual
complaints were also recorded. RESULTS: The analysis of intent-to-treat
population comprised 75 patients in the nepafenac group and 77 patients in the
control group. Compared with the control regimen, add-on nepafenac resulted in
statistically significant reductions in the following parameters: change in
macular volume at 3 weeks and 6 weeks (P<.001), proportion of patients with more
than 10 MUm of swelling in the central macula at 3 weeks (P<.0001) and 6 weeks
(P=.02), mean laser flare intensity at 1 day (P=.029), pain during the first 24
hours postoperatively (P<.0001), and ocular discomfort and photophobia during the
first 3 postoperative weeks (P=.0058 and P=.0052, respectively). CONCLUSION: The
combination of topical nepafenac and steroid treatment reduced subclinical
macular swelling and inflammation as well as subjective complaints, indicating it
is an efficient antiinflammatory regimen after cataract surgery. FINANCIAL
DISCLOSURE: No author has a financial or proprietary interest in any material or
method mentioned.
PMID- 25135543
TI - Evaluating teaching methods: validation of an evaluation tool for hydrodissection
and phacoemulsification portions of cataract surgery.
AB - PURPOSE: To develop and assess the validity of an evaluation tool to assess
quantitatively the hydrodissection and phacoemulsification portions of cataract
surgery performed by residents. DESIGN: Case series. SETTING: Jules Stein Eye
Institute, Olive View-UCLA Medical Center, and Veterans Administration Medical
Center, Los Angeles, California, USA. METHODS: The UCLA ophthalmology faculty
members were surveyed and the literature was reviewed to develop a grading tool
consisting of 15 questions to evaluate surgical technique, including questions
from the Global Rating Assessment of Skills in Intraocular Surgery and from the
International Council of Ophthalmology's Ophthalmology Surgical Competency
Assessment Rubric. Video clips of the hydrodissection and phacoemulsification
portions of cataract surgery performed by 1 postgraduate year 2 (PGY2) resident,
1 PGY3 resident, 2 PGY4 residents, and an advanced surgeon were independently
graded in a masked fashion by an 8-member faculty panel. RESULTS: Eleven of the
15 questions had a significant association with surgical experience level (P<.05,
analysis of variance). Interobserver variability in grading yielded intraclass
correlation coefficients between 0.28 and 0.72. The questions with the lowest
interobserver variability were hydrodissection questions on instrument handling,
flow of operation, and nucleus rotation. Nucleus cracking also had low
variability. Less directly visible tasks, especially 3-dimensional tasks, had
wider interobserver variability. CONCLUSIONS: Surgical performance can be validly
measured using an evaluation tool. Improved videography and studies to identify
the best questions for evaluating each step of cataract surgery may help
ophthalmic educators more precisely measure training outcomes for improving
teaching interventions. FINANCIAL DISCLOSURE: No author has a financial or
proprietary interest in any material or method mentioned.
PMID- 25135544
TI - Textural interface opacity after Descemet-stripping automated endothelial
keratoplasty.
AB - PURPOSE: To describe cases of interface haze, also known as textural interface
opacity, after Descemet-stripping automated endothelial keratoplasty (DSAEK).
SETTING: Department of Cornea, External Disease, and Refractive Surgery Service,
Duke Eye Center, Durham, North Carolina, USA. DESIGN: Retrospective case series.
METHODS: Patients' clinical and demographic characteristics, cornea donor
information, surgical technique, histopathology, and anterior segment optical
coherence tomography (OCT) were reviewed retrospectively and clinical outcomes
reported. RESULTS: The interface haze that developed after DSAEK comprised 2
types of textural interface opacity; that is, total (11 cases) and partial (3
cases). The time of onset of textural interface opacity ranged from 1 day to 7
weeks postoperatively. Although most patients with textural interface opacity
showed improvement, with a corrected distance visual acuity better than 20/50, 3
had persistent decreased visual acuity and required repeat DSAEK. Seven eyes had
concurrent phacoemulsification with intraocular lens implantation and DSAEK. The
corneal graft was inserted with an Endoserter device in 11 eyes, an insertion
forceps in 2 eyes, and a cystotome needle in 1 eye. Histopathology of the grafts
of eyes that required repeat DSAEK showed no inflammation, no foreign-body
deposit, and no fibrosis. Anterior segment OCT showed increased hyperreflectivity
in the interface. CONCLUSIONS: Although the etiology of textural interface
opacity is unclear, it may be related to retained ophthalmic viscosurgical device
(OVD) or an adhesive property of the OVD used during the surgery. Although most
cases resolve with time, repeat DSAEK may be an effective treatment for
refractory cases. FINANCIAL DISCLOSURE: Dr. Kim is a consultant to Ocular
Systems, Inc. No other author has a financial or proprietary interest in any
material or method mentioned.
PMID- 25135545
TI - Prevention of capsule opacification after accommodating lens refilling: pilot
study of strategies evaluated in a monkey model.
AB - PURPOSE: To test 2 strategies to prevent capsule opacification after
accommodating lens refilling in a rhesus monkey model. SETTING: Animal laboratory
and laboratory of European university medical centers. DESIGN: Experimental
study. METHODS: Six rhesus monkeys had refilling of the lens capsular bag. In the
first strategy, before it was filled with a silicone polymer, the capsular bag
was treated with noncommercial sodium hyaluronate 1.0% containing cytotoxic
substances. In the second strategy, the capsular bag was filled with clinically
used sodium hyaluronate 1.0% (Healon) after treatment with actinomycin-D.
Slitlamp inspection was performed during a follow-up of 40 to 50 weeks. After
enucleation, magnetic resonance images were obtained and confocal fluorescence
imaging was performed. RESULTS: Using the first strategy, capsule opacification
developed in all eyes. Using the second strategy, 1 monkey did not develop
capsule opacification after a 9-month follow-up. In a second monkey, the lens
capsule remained clear for 3 months, after which the hyaluronate refill material
was exchanged with a silicone polymer and capsule opacification developed.
Combining these results with those in a previous study, the difference in
opacification between silicone and sodium hyaluronate as refilling materials was
statistically significant (P<.01). CONCLUSIONS: That no capsular bag fibrosis
occurred in the presence of hyaluronate suggests that the properties of
hyaluronate are the reason that remaining lens epithelial cells do not develop
into fibrotic cells. The choice of a suitable lens-refilling material prevents
the development of capsule opacification. FINANCIAL DISCLOSURE: Mr. Terwee was an
employee of Abbott Medical Optics B.V. during the study period. No other author
has a financial or proprietary interest in any material or method mentioned.
PMID- 25135547
TI - Optimum on-time duty cycle for micropulse technology.
AB - PURPOSE: To evaluate the optimum on time for the most efficient removal of lens
fragments using micropulsed ultrasound (US). SETTING: John A. Moran Eye Center
Laboratories, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental
study. METHODS: Twenty porcine lens nuclei were soaked in formalin for 2 hours
and then divided into 2.0 mm cubes. Using an US machine with a 0.9 mm bent and a
30-degree bevel tip, the on time was varied every millisecond (ms) from 2 ms to
10 ms with the off time kept constant at 10 ms. Efficiency (time to lens removal)
and chatter (number of lens fragment repulsions from the tip) were determined.
RESULTS: The most efficient phacoemulsification was achieved with an on time of 6
ms. On times shorter than 6 ms were significantly less efficient (R2=.82, P=.04).
Greater on times did not result in a significant difference in efficiency
(R2=.03, P=.78) but did appear to have more chatter events when comparing 9 to 10
ms with 2 to 8 ms (P<.0001). CONCLUSIONS: With micropulsed longitudinal US, a 6
ms on time was equally as efficient as longer on times, while shorter on times (2
to 5 ms) had decreased efficiency. At 9 ms and 10 ms on time, significantly more
chatter was noted. Therefore, to maximize phacoemulsification, an on-time setting
of 6 ms is recommended. FINANCIAL DISCLOSURE: No author has a financial or
proprietary interest in any material or method mentioned.
PMID- 25135546
TI - Biointerface multiparametric study of intraocular lens acrylic materials.
AB - PURPOSE: To compare hydrophilic and hydrophobic acrylic materials designed for
intraocular lenses in a multiparametric investigation in a liquid environment to
highlight their properties in terms of adhesion forces, lens epithelial cell
(LEC) adhesion, and tissue response as indicators of the risk for posterior
capsule opacification (PCO) development. SETTING: University of Liege, Liege,
Belgium. DESIGN: Experimental study. METHODS: The hydrophobicity and surface
adhesion force were assessed using contact-angle and atomic force microscopy
measurements. The bioadhesiveness of the disks and the tissue response were
determined by in vitro experiments using bovine serum albumin and porcine LECs
and by in vivo rabbit subcutaneous implantation, respectively. RESULTS:
Increasing surface hydrophobicity led to a greater surface-adhesion force and
greater LEC adhesion. After 1 month, the rabbit subcutaneous implants showed a
similar thin layer of fibrous capsule surrounding the disks without extensive
inflammation. A layer of rounded cells in contact with disks was detected on the
hydrophobic samples only. CONCLUSIONS: Hydrophobic acrylic disks that have been
associated with a reduced risk for PCO in clinical studies showed increased
tackiness. FINANCIAL DISCLOSURES: Proprietary or commercial disclosures are
listed after the references.
PMID- 25135548
TI - Microincisions in cataract surgery.
AB - Improvements in phacoemulsification technology and instrumentation and
intraocular lens materials and design have enabled cataract surgery to be
performed through incisions smaller than 2.0 mm in external width. This evolution
has occurred over time, with new challenges arising at each step of the decrease
in incision size. This article reviews the current trend of using increasingly
smaller incisions to perform phacoemulsification. Specifically, each facet of
phacoemulsification is briefly reviewed from a historical context and then
evaluated predominantly from a current perspective to better understand the
development of the microincision in cataract surgery. The goal is to help the
operating surgeon recognize the potential benefits as well as the potential
weaknesses of the smaller incision. FINANCIAL DISCLOSURES: Proprietary or
commercial disclosures are listed after the references.
PMID- 25135549
TI - Corneal collagen crosslinking failure in a patient with floppy eyelid syndrome.
AB - A 30-year-old man with bilateral floppy eyelid syndrome (more prominent in the
left eye) and progressive keratoconus had corneal collagen crosslinking (CXL) in
both eyes. No intraoperative or early postoperative complications were found.
Topographic examination after CXL revealed a continuous increase in the
keratometric values in the left eye in which the floppy eyelid syndrome was more
prominent, indicating keratoconus progression (CXL failure). The fellow eye with
the less prominent floppy eyelid syndrome remained stable during the follow-up
period. Floppy eyelid syndrome could be a risk factor for CXL failure. FINANCIAL
DISCLOSURE: No author has a financial or proprietary interest in any material or
method mentioned.
PMID- 25135550
TI - Spontaneous bilateral anterior partial in-the-bag intraocular lens dislocation
following routine annual eye examination.
AB - We present the case of an 81-year-old man with pseudoexfoliation syndrome (PXF)
in whom spontaneous bilateral anterior partial in-the-bag intraocular lens (IOL)
dislocation was diagnosed following a routine dilated examination that
demonstrated only mild pseudophacodonesis with no evidence of subluxation.
Uneventful cataract surgery with placement of single-piece hydrophobic acrylic
posterior chamber IOLs had been performed in both eyes 7 years previously.
Bilateral IOL repositioning with scleral fixation was performed to correct the
dislocation. Postoperative examinations showed remarkable improvement in visual
acuity and IOL stability. We hypothesize that zonular weakness secondary to PXF
predisposed the patient to bilateral IOL partial dislocation. Pupil dilation in
the setting of mild pseudophacodonesis at the time of routine examination may
have been a precipitating factor. To our knowledge, bilateral IOL
subluxation/dislocation has been described in a limited number of case reports.
FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any
material or method mentioned.
PMID- 25135551
TI - Unsutured phakic implantation of a black intraocular lens in the sulcus to treat
leukocoria.
AB - We describe a 40-year-old woman with von Hippel-Lindau syndrome, secondary
chronic exudative retinal detachment, and white cataract with consequent
leukocoria. Because the cataract was contracted and calcified, a black Morcher
85F poly(methyl methacrylate) IOL was implanted in the ciliary sulcus anterior to
the lens to prevent posterior capsule rupture and potential destabilization of
the retinal detachment with a risk for phthisis. Excellent centration of the
black IOL was achieved with good cosmetic outcome and without postoperative
uveitis or glaucoma. We suggest that this is a rare indication for implantation
of an IOL designed for the sulcus but in the presence of the crystalline lens.
This approach makes IOL removal, if necessary at a later date, relatively
straightforward. FINANCIAL DISCLOSURE: No author has a financial or proprietary
interest in any material or method mentioned.
PMID- 25135552
TI - Simple method to restore a fractured 10-0 polypropylene suture using a single
fisherman's knot.
PMID- 25135553
TI - New benchmark in preventing phacoemulsification-related endophthalmitis.
PMID- 25135554
TI - Refractive Surgical Question: September consultation #1.
PMID- 25135555
TI - September consultation #2.
PMID- 25135556
TI - September consultation #3.
PMID- 25135557
TI - September consultation #5.
PMID- 25135558
TI - September consultation #4.
PMID- 25135559
TI - September consultation #7.
PMID- 25135560
TI - September consultation #6.
PMID- 25135567
TI - Immunology: IL-22 and metabolic disease.
PMID- 25135568
TI - Cardiovascular endocrinology: controversy--cardiovascular effects of calcium
supplementation.
AB - Of late, clinical trial data, meta-analyses and observational studies have caused
concern that the use of calcium supplements might increase the risk of myocardial
infarction and stroke. A new meta-analysis suggests that there is no problem with
calcium supplements, but as the analysis includes controversial data omitted from
previous analyses, the debate will continue.
PMID- 25135570
TI - Obesity: Targeting fat deposits--one step closer.
PMID- 25135574
TI - Mode of delivery and the probability of subsequent childbearing: a population
based register study.
AB - OBJECTIVE: To investigate the relationship between mode of first delivery and
probability of subsequent childbearing. DESIGN: Population-based study. SETTING:
Nationwide study in Sweden. POPULATION: A cohort of 771 690 women who delivered
their first singleton infant in Sweden between 1992 and 2010. METHODS: Using
Cox's proportional-hazards regression models, risks of subsequent childbearing
were compared across four modes of delivery. Hazard ratios (HRs) were calculated,
using 95% confidence intervals (95% CIs). MAIN OUTCOME MEASURES: Probability of
having a second and third child; interpregnancy interval. RESULTS: Compared with
women who had a spontaneous vaginal first delivery, women who delivered by vacuum
extraction were less likely to have a second pregnancy (HR 0.96, 95% CI 0.95
0.97), and the probabilities of a second childbirth were substantially lower
among women with a previous emergency caesarean section (HR 0.85, 95% CI 0.84
0.86) or an elective caesarean section (HR 0.82, 95% CI 0.80-0.83). There were no
clinically important differences in the median time between first and second
pregnancy by mode of first delivery. Compared with women younger than 30 years of
age, older women were more negatively affected by a vacuum extraction with
respect to the probability of having a second child. A primary vacuum extraction
decreased the probability of having a third child by 4%, but having two
consecutive vacuum extraction deliveries did not further alter the probability.
CONCLUSIONS: A first delivery by vacuum extraction does not reduce the
probability of subsequent childbearing to the same extent as a first delivery by
emergency or elective caesarean section.
PMID- 25135576
TI - Crystal transformation synthesis of a highly stable fluorescent 3D indium
tetranuclear {In4(MU2-OH)3} building block based metal organic framework through
a dinuclear complex.
AB - A rare 3D tetranuclear {In4(MU2-OH)3} building block based MOF {[In4/3(MU2
OH)(2,6-pydc)(1,4-bda)0.5(H2O)].2H2O}n (2) was obtained through a crystal
transformation from a dimeric complex In3(2,6-pydc)3(1,4-bda)1.5(H2O)6 (1). With
a 2D + 3D -> 3D compact structure, 2 retains crystallinity in boiling water and
organic solvents, exhibiting exceptional fluorescence quenching behaviour for the
DMSO molecule.
PMID- 25135573
TI - Thyroid hormone receptors and resistance to thyroid hormone disorders.
AB - Thyroid hormone action is predominantly mediated by thyroid hormone receptors
(THRs), which are encoded by the thyroid hormone receptor alpha (THRA) and
thyroid hormone receptor beta (THRB) genes. Patients with mutations in THRB
present with resistance to thyroid hormone beta (RTHbeta), which is a disorder
characterized by elevated levels of thyroid hormone, normal or elevated levels of
TSH and goitre. Mechanistic insights about the contributions of THRbeta to
various processes, including colour vision, development of the cochlea and the
cerebellum, and normal functioning of the adult liver and heart, have been
obtained by either introducing human THRB mutations into mice or by deletion of
the mouse Thrb gene. The introduction of the same mutations that mimic human
THRbeta alterations into the mouse Thra and Thrb genes resulted in distinct
phenotypes, which suggests that THRA and THRB might have non-overlapping
functions in human physiology. These studies also suggested that THRA mutations
might not be lethal. Seven patients with mutations in THRalpha have since been
described. These patients have RTHalpha and presented with major abnormalities in
growth and gastrointestinal function. The hypothalamic-pituitary-thyroid axis in
these individuals is minimally affected, which suggests that the central T3
feedback loop is not impaired in patients with RTHalpha, in stark contrast to
patients with RTHbeta.
PMID- 25135575
TI - Isolation of arginine kinase from Apis cerana cerana and its possible involvement
in response to adverse stress.
AB - Arginine kinases (AK) in invertebrates play the same role as creatine kinases in
vertebrates. Both proteins are important for energy metabolism, and previous
studies on AK focused on this attribute. In this study, the arginine kinase gene
was isolated from Apis cerana cerana and was named AccAK. A 5'-flanking region
was also cloned and shown to contain abundant putative binding sites for
transcription factors related to development and response to adverse stress. We
imitated several abiotic and biotic stresses suffered by A. cerana cerana during
their life, including heavy metals, pesticides, herbicides, heat, cold, oxidants,
antioxidants, ecdysone, and Ascosphaera apis and then studied the expression
patterns of AccAK after these treatments. AccAK was upregulated under all
conditions, and, in some conditions, this response was very pronounced. Western
blot and AccAK enzyme activity assays confirmed the results. In addition, a disc
diffusion assay showed that overexpression of AccAK reduced the resistance of
Escherichia coli cells to multiple adverse stresses. Taken together, our results
indicated that AccAK may be involved of great significance in response to adverse
abiotic and biotic stresses.
PMID- 25135577
TI - Thyroglossal duct cysts: 20 years' experience (1992-2011).
AB - The objective of the present study is to report on the clinical course and
management of thyroglossal duct cysts. Retrospective review of all patients who
underwent surgery for thyroglossal duct cysts between 2000 and 2013 at a tertiary
referral center was carried out. The operations were performed using a
modification of the Sistrunk operation: transcervical cystectomy, partial
dissection of the hyoid bone, and dissection of all tracts identified during
surgery. A total of 352 patients (176 men, 176 women) underwent surgery for a
cyst (n = 282) or discharging sinus (n = 70). The mean age for the incidence of
cysts was 26 years. Four of the patients (1.4 %) had a papillary thyroid
carcinoma in the epithelium of the cyst. The follow-up period ranged from 7
months to 10 years. The overall recurrence rate was 4.5 %. Resection is often
regarded as an elective surgical procedure in patients with thyroglossal duct
cysts, but surgery should always be considered. Papillary thyroid carcinoma in
the epithelium of the cyst is a rare but possible differential diagnosis.
Dissection of all tracts found is recommended and partial dissection of the hyoid
bone is mandatory. Dissection of the foramen cecum is not imperative. The
recurrence rates with this approach are comparable to more extensive methods such
as those described by Sistrunk.
PMID- 25135579
TI - Meeting report: consensus recommendations for a research agenda in exercise in
solid organ transplantation.
AB - With improved survival rates in solid organ transplantation there has been an
increased focus on long-term outcomes following transplant, including physical
function, health-related quality-of-life and cardiovascular mortality. Exercise
training has the potential to affect these outcomes, however, research on the
optimal timing, type, dose of exercise, mode of delivery and relevant outcomes is
limited. This article provides a summary of a 2-day meeting held in April 2013
(Toronto, Canada) in which a multi-disciplinary group of clinicians, researchers,
administrators and patient representatives engaged in knowledge exchange and
discussion of key issues in exercise in solid organ transplant (SOT). The
outcomes from the meeting were the development of top research priorities and a
research agenda for exercise in SOT, which included the need for larger scale,
multi-center intervention studies, development of standardized outcomes for
physical function and surrogate measures for clinical trials, examining novel
modes of exercise delivery and novel outcomes from exercise training studies such
as immunity, infection, cognition and economic outcomes. The development and
dissemination of "expert consensus guidelines," synthesizing both the best
available evidence and expert opinion was prioritized as a key step toward
improving program delivery.
PMID- 25135578
TI - Objective assessment of persistent rhinitis in Chinese and its relationship with
serum indicators.
AB - Persistent rhinitis (PR) is a chronic disease that affects millions of people.
However, it lacks of a useful method, which can indicate the actual severity of
the inflammation in PR patients. This study was designed to seek an examination
which could reflect the actual severity of PR disease. The serum Phadiatop test,
ECP level, four-phase rhinomanometry, and acoustic rhinometry were assessed in 91
adult patients with PR and 10 healthy controls. The serum total IgE was
determined in some of the patients and all of the controls. The patients were
divided into four groups: ARWO, ARWTO, NARWO and NARWTO. 40% (22/55) of AR and
33.3% (13/36) of NAR patients never complained of persistent nasal obstruction.
Serum ECP levels were increased in the ARWO group. Serum total IgE was
significantly elevated in the AR groups. MCA(1-Min) and MCA(1-T) were
significantly reduced in the ARWO, ARWTO, and NARWO groups. NV(6-Min) and NV(6-T)
were decreased in all PR groups, but only some of these differences were
significant. In the ARWO group, MCA(2-Min) (r = -0.252), MCA(2-T) (r = -0.377),
NV(6-Min) (r = -0.32), and NV(6-T) (r = -0.311) had significant relationships
with serum ECP. We recommend acoustic rhinometry as a useful routine tool for the
diagnosis of PR, even among patients without persistent subjective nasal
obstruction. This technique might reveal the actual status of nasal congestion.
An elevated serum ECP level might indicate severe AR and is negatively correlated
with the results of acoustic rhinometry.
PMID- 25135580
TI - The role of patient-mode high-resolution peripheral quantitative computed
tomography indices in the prediction of failure strength of the elderly women's
thoracic vertebral body.
AB - The correlations between the failure load of 20 T12 vertebral bodies, their
patient-mode high-resolution peripheral quantitative computed tomography (HR
pQCT) indices, and the L1 areal bone mineral density (aBMD) were investigated.
For the prediction of the T12 vertebral failure load, the T12 HR-pQCT
microarchitectural parameters added significant information to that of L1 aBMD
and to that of cortical BMD, but not to that of T12 vertebral BMD and not to that
of T12 trabecular BMD. INTRODUCTION: HR-pQCT is a new in vivo imaging technique
for assessing the three-dimensional microarchitecture of cortical and trabecular
bone at the distal radius and tibia. But little is known about this technique in
the direct measurement of vertebral body. METHODS: Twenty female donors with the
mean age of 80.1 (7.6) years were included in the study. Dual X-ray
absorptiometry of the lumbar spine and femur was performed. The spinal specimens
(T11/T12/L1) were dissected, scanned using HR-pQCT scanner, and mechanically
tested under 4 degrees wedge compression. The L1 aBMD, T12 patient-mode HR-pQCT
indices, and T12 vertebral failure loads were analyzed. RESULTS: For the
prediction of vertebral failure load, the inclusion of BV/TV into L1 aBMD was the
best model (R (2) = 0.52), Tb.N and Tb.Sp added significant information to the L1
aBMD and to the cortical BMD, but none of the vertebral microarchitectural
parameters yielded additional significant information to the trabecular BMD (or
BV/TV) and to the vertebral BMD. CONCLUSION: Vertebral microarchitectural
parameters obtained from the patient-mode HR-pQCT analysis provide significant
information on bone strength complementary to that of aBMD and to that of
cortical BMD, but not to that of vertebral BMD and not to that of trabecular BMD.
PMID- 25135581
TI - Should Men and Women be Managed Differently in Glaucoma?
AB - INTRODUCTION: To assess differences in associations of ocular perfusion pressure
(OPP) as well as retinal and retrobulbar blood flow between men and women with
primary open angle glaucoma (OAG). METHODS: A total of 116 patients with OAG (age
66.9 +/- 10.9 years, 70 females) participating in the Indianapolis Glaucoma
Progression Study were assessed for OPP, retinal microcirculation, and
retrobulbar blood flow. Confocal scanning laser Doppler flowmetry measured
peripapillary retinal capillary blood flow. Color Doppler imaging measured peak
systolic (PSV) and diastolic blood flow velocities and vascular resistance in the
ophthalmic (OA), central retinal (CRA), and nasal and temporal short posterior
ciliary arteries (N/T PCA). Bivariate Spearman correlation and multivariate
linear regression analyses were performed. RESULTS: In female patients with OAG,
inferior retinal capillary flow was associated with OPP (r = 0.246, P = 0.044).
In men, superior and inferior sector retinal blood flow was associated with OPP
(r = -0.402, P = 0.006 and r = -0.357, P = 0.016, respectively). There was no
statistically significant association between OPP and retrobulbar blood vessel
flow velocities in male patients with OAG but there was an association between OA
and TPCA PSV and OPP in female patients with OAG (r = 0.290, P = 0.015 and r =
0.357, P = 0.002, respectively). In female patients with OAG, multivariate
regression showed no statistically significant effect of any variable on the
superior retinal capillary blood flow, with CRA PSV as a sole predictor to the
inferior retinal sector (partial rho = 0.302, P = 0.015) and in male patients
with OAG, superior sector retinal capillary blood flow was independently
associated with intraocular pressure (partial rho = -0.371, P = 0.016) and OPP
(partial rho = -0.456, P = 0.002) with a trend of association with OPP in the
inferior retina (partial rho = -0.301, P = 0.053). CONCLUSIONS: There was a
positive linear association between retinal microcirculation and OPP in females
and a negative association in males. Male and female patients with OAG may differ
in their vascular autoregulation in response to changes in OPP.
PMID- 25135582
TI - Ophthalmic complications of dengue Fever: a systematic review.
AB - INTRODUCTION: In recent years there has been a spurt of peer-reviewed
publications on the ophthalmic complications of dengue fever. The authors aim to
review the ocular manifestations, utility of relevant diagnostic tests,
management, prognosis, and sequelae of dengue-related ocular complications.
METHODS: A comprehensive literature search was conducted on Medline, PubMed, and
Google Scholar databases. Only articles published or translated into the English
language were considered, and key data from the full article of each paper was
extracted and evaluated. RESULTS: The authors' search yielded 29 articles. A
total of 686 patients with a mean age of 33.4 years (range 14-73 years) were
included. Blurring of vision was the most common presenting symptom followed by
scotoma. Ocular findings were mostly seen in the posterior pole of the fundus,
manifesting as retinal hemorrhages, macular edema, foveolitis, vasculitis, and
optic neuropathy. Most patients with dengue-related ophthalmic complications
recover spontaneously without any treatment. Patients with severe visual loss or
bilateral involvement were treated with systemic steroids and occasionally
immunoglobulins. Prognosis of dengue-related ophthalmic complications is
favorable; almost all patients had normal or showed improvement in visual acuity
and complete resolution of dengue ophthalmic complications was noted in almost
all cases. CONCLUSION: The pathological process of dengue ophthalmic
complications is complex and clinical manifestations varied. Ophthalmic
complications are usually seen in young adults who often present at the nadir of
thrombocytopenia. Despite good recovery of vision and resolution of clinical
signs in most patients, ophthalmologists and physicians should be aware and
vigilant as isolated reports of cases of dengue ophthalmic complications with
poor visual acuity refractory to treatment have been reported.
PMID- 25135583
TI - Practical management of retinal vein occlusions.
AB - Retinal vein occlusion (RVO) is the second most common cause of visual impairment
due to retinal disease after diabetic retinopathy. Nowadays, the introduction of
new, powerful diagnostic tools, such as spectral domain optical coherence
tomography, and the widespread diffusion of intravitreal drugs, such as vascular
endothelial grow factor inhibitors or implantable steroids, have dramatically
changed the management and prognosis of RVO. The authors aim to summarize and
review the main clinical, diagnostic, and therapeutic aspects of this condition.
The authors conducted a review of the most relevant clinical trials and
observational studies published within the last 30 years using a keyword search
of MEDLINE, EMBASE, Current Contents, and Cochrane Library. Furthermore, for all
treatments discussed, the level of evidence supporting its use, as per the US
Preventive Task Force Ranking System, is provided.
PMID- 25135584
TI - Multiple layers lens capsule true exfoliation in patient with primary angle
closure glaucoma.
AB - INTRODUCTION: True exfoliation of lens capsule is a relatively rare disorder that
has a thin, fluttering membrane in the anterior chamber, mainly located in the
pupil area, which is believed to have split from the anterior lens capsule. CASE
REPORT: The authors present here a patient with true exfoliation and primary
angle closure glaucoma in both eyes, the ultrastructure of one eye revealed that
the delaminated membrane was composed of more than two layers in itself.
CONCLUSION: Lens capsule true exfoliation could happen in patient with primary
angle closure glaucoma, with more than two layers in itself.
PMID- 25135585
TI - Topical isopropyl unoprostone for retinitis pigmentosa: microperimetric results
of the phase 2 clinical study.
AB - INTRODUCTION: The purpose of this study was to determine whether topical 0.15%
isopropyl unoprostone (IU), a BK-channel activator, could improve or maintain the
central retinal sensitivity in patients with middle- to late-stage retinitis
pigmentosa (RP). IU was approved for glaucoma and ocular hypertension in 1994.
The drug re-profiling strategy is one of the effective ways to develop safe drugs
for patients with RP. METHODS: A randomized, double-blind, and placebo-controlled
phase II safety/efficacy trial was conducted. One hundred and nine patients with
middle- to late-stage RP having a visual acuity of >=0.5 were studied at six
ophthalmological centers in Japan. The treatments of IU/day were divided into
three groups: placebo group; two-drop group; and four-drop group for 24 weeks.
The primary outcome measure was changes in the retinal sensitivity from baseline
in the central 2 degrees determined by MP-1 microperimetry (MP-1, Nidek, Japan).
The secondary outcomes were changes in best-correct visual acuity, contrast
sensitivity, retinal sensitivity of the central 10 degrees by MP-1, mean
deviation (MD) by a Humphrey field analyzer (HFA; Carl Zeiss Meditec, Dublin, CA,
USA) 10-2, and the Visual Functioning Questionnaire 25 (VFQ-25) questionnaire
scores. RESULTS: There was a tendency for a dose-dependent responsiveness in
retinal sensitivity in the central 2 degrees , MD, and total VFQ-25 score after
24 weeks of IU instillation by a simple linear regression analysis. A stratified
analysis showed a significant dose-dependent responsiveness of the 2 degrees
central retinal sensitivity in more advanced patients (P = 0.028). The number of
patients having a >=4 dB decrease in the primary outcome measure was
significantly fewer in the four-drop group than in the placebo group (P = 0.02).
No adverse reactions were observed. CONCLUSIONS: A higher dose of IU can delay
progression of the central retinal sensitivity decrease through an improvement of
retinal sensitivity.
PMID- 25135586
TI - Effect of short-term oral valproic Acid on vision and visual field in retinitis
pigmentosa.
AB - INTRODUCTION: The aim of this study was to evaluate the effect of short-term oral
valproic acid (VPA) on the vision and visual fields of patients with retinitis
pigmentosa (RP). METHODS: In this prospective, nonrandomized trial, 10 patients
(20 eyes) with established RP were treated with oral VPA 500 mg/day for 3 months.
Visual acuity was monitored using the Snellen chart and values were converted
into Early Treatment Diabetic Retinopathy Study chart and logarithm of the
minimum angle of resolution (logMAR) equivalents. Visual field changes were
evaluated using the Humphrey visual field analyzer (30-2 SITA standard test
protocol). RESULTS: Mean visual acuity was significantly improved from a
pretreatment value of 20/72 (logMAR 0.560 +/- 0.488) to 20/65 (logMAR 0.513 +/-
0.422) after 3 months of treatment (P = 0.006). Vision improved by at least one
line or more than one line in 10 eyes, and remained stable in the other 10 eyes.
Visual field improvement was noted in nine eyes (P < 0.05, chi(2) test), nine
showing no significant field change and in two visual fields could not be
recorded due to poor vision. CONCLUSION: Short-term (3-month) treatment with VPA
improves the vision and visual field of patients with RP.
PMID- 25135588
TI - Do We Currently Have Guidelines to Select an Adequate Prosthetic Valve to
Surgically Treat Active Infective Endocarditis?
AB - Active infective endocarditis is a devastating disease with high morbidity and
mortality, which generally needs surgery and appropriate antimicrobial therapy.
Selecting an adequate valve prosthesis is a central issue during surgery. This
editorial discusses the recent literature available on this important topic.
PMID- 25135587
TI - Ivabradine Versus Beta-Blockers in Patients with Conduction Abnormalities or Left
Ventricular Dysfunction Undergoing Cardiac Surgery.
AB - INTRODUCTION: In patients with conduction abnormalities or left ventricle (LV)
dysfunction the use of beta-blockers for post cardiac surgery rhythm control is
difficult and controversial, with a paucity of information about other drugs such
ivabradine used postoperatively. The objective of this study was to compare the
efficacy and safety of ivabradine versus metoprolol used perioperatively in
cardiac surgery patients with conduction abnormalities or LV systolic
dysfunction. METHODS: This was an open-label, randomized clinical trial enrolling
527 patients with conduction abnormalities or LV systolic dysfunction undergoing
coronary artery bypass grafting or valvular replacement, randomized to take
ivabradine or metoprolol, or metoprolol plus ivabradine. The primary endpoints
were the composites of 30-day mortality, in-hospital atrial fibrillation (AF), in
hospital three-degree atrioventricular block and need for pacing, in-hospital
worsening heart failure (HF; safety endpoints), duration of hospital stay and
immobilization and the above endpoint plus in-hospital bradycardia,
gastrointestinal symptoms, sleep disturbances, cold extremities (efficacy plus
safety endpoint). RESULTS: Heart rate reduction and prevention of postoperative
AF or tachyarrhythmia with combined therapy was more effective than with
metoprolol or ivabradine alone during the immediate postoperative management of
cardiac surgery patients. In the Ivabradine group, the frequency of early
postoperative pacing and HF worsening was smaller than in the Metoprolol group
and in combined therapy group. The frequency of primary combined endpoint was
lower in the combined Ivabradine + Metoprolol group compared with the monotherapy
groups. CONCLUSION: Considering efficacy and safety, the cardiac rhythm reduction
after open heart surgery in patients with conduction abnormalities or LV
dysfunction with ivabradine plus metoprolol emerged as the best treatment in this
trial.
PMID- 25135589
TI - Aorta-to-Left Atrial Fistula Caused by Air Gun Pellet Cardiac Injury.
AB - Abnormal communication between the ascending aorta and the cardiac chambers is
rare, diverse in origin, and can be congenital or acquired. We report a case of a
10-year-old boy with acquired aorta-to-left atrial fistula associated with an air
gun pellet injury and his successful treatment.
PMID- 25135590
TI - Prognosis of Troponin-Positive Patients with Non-Obstructive Coronary Artery
Disease.
AB - INTRODUCTION: Troponin elevation is an independent risk factor for mortality, but
the prognosis of patients with troponin elevation and non-obstructive coronary
artery disease (CAD) is unknown. Recent data have suggested an increased risk of
mortality. This study was performed to further investigate the outcomes of
troponin-positive patients with obstructive and non-obstructive CAD. METHODS: A
retrospective cohort analysis was performed of all patients with raised troponin
presenting to Kettering General Hospital (January 2010 to December 2011, n =
1,351). The patients who had angiograms were stratified anatomically into
obstructive CAD and non-obstructive CAD (<=50% stenosis). The obstructive CAD
group (O-CAD) was sub-analyzed by management strategy: emergency re
vascularization (<12 h), urgent, delayed, and medically managed. Patients with
non-obstructive CAD were grouped by the cause of the raised troponin if this
could be identified (NO-CAD-I) or cause remained unidentified (NO-CAD-U). The
major adverse cardiac and cerebrovascular event (MACCE) and mortality rates were
calculated at 30 days and 1-year follow-up. RESULTS: There was a preponderance of
hypertension and severe renal impairment in the non-obstructive CAD group. The
patients with NO-CAD-U were a low-risk group (MACCE at 1-year follow-up = 0). The
remaining NO-CAD-I group had a similar risk to the O-CAD group for MACCE and
mortality at 30 days and 1-year follow-up. In fact, at 1-year follow-up, the NO
CAD-I patients when compared with the subgroups of O-CAD, had higher MACCE rates
and mortality compared with the emergency re-vascularized group [MACCE: relative
risk (RR) (95% CI) = 2.27 (1.29-3.40), P = 0.0047; mortality: RR (95% CI) = 2.08
(1.10-3.93), P = 0.024]. This was driven by higher risk non-cardiac death [RR
(95% CI) = 4.10 (1.53-10.99), P = 0.005]. CONCLUSION: Patients with identified
cause for raised troponin and non-obstructive CAD are at equivalent risk of MACCE
and mortality at 30 days and 1-year follow-up compared to those with obstructive
CAD.
PMID- 25135591
TI - The Changing Role for Endomyocardial Biopsy in the Diagnosis of Giant-Cell
Myocarditis.
AB - Endomyocardial biopsy (EMB) is central to the diagnosis of giant-cell myocarditis
(GCM) and planning further management. There is, however, no guideline-directed
recommendation on re-biopsy or left ventricular EMB in a suspected case of acute,
fulminant myocarditis following an indeterminate first biopsy. This manuscript
illustrates, with a case, the changing role for EMB in the current era in the
diagnosis of GCM.
PMID- 25135592
TI - Perturbation of the interaction between Gal4p and Gal80p of the Saccharomyces
cerevisiae GAL switch results in altered responses to galactose and glucose.
AB - In S. cerevisiae, following the Whole Genome Duplication (WGD), GAL1-encoded
galactokinase retained its signal transduction function but lost basal
expression. On the other hand, its paralogue GAL3, lost kinase activity but
retained its signalling function and basal expression, thus making it
indispensable for the rapid induction of the S. cerevisiae GAL switch. However, a
gal3Delta strain exhibits delayed growth kinetics due to the redundant signalling
function of GAL1. The subfunctionalization between the paralogues GAL1 and GAL3
is due to expression divergence and is proposed to be due to the alteration in
the Upstream Activating Sequences (UASG ). We demonstrate that the GAL switch
becomes independent of GAL3 by altering the interaction between Gal4p and Gal80p
without altering the configuration of UASG . In addition to the above, the
altered switch of S. cerevisiae loses ultrasensitivity and stringent glucose
repression. These changes caused an increase in fitness in the disaccharide
melibiose at the expense of a decrease in fitness in galactose. The above altered
features of the ScGAL switch are similar to the features of the GAL switch of K.
lactis that diverged from S. cerevisiae before the WGD.
PMID- 25135593
TI - Switching treatments in haemophilia: is there a risk of inhibitor development?
AB - Patients with haemophilia A (and their physicians) may be reluctant to switch
factor VIII (FVIII) concentrates, often due to concerns about increasing the risk
of inhibitors; this reluctance to switch may contribute to patients missing the
clinical benefits provided by the arrival of new factor VIII products. This topic
was explored at the Eleventh Zurich Haemophilia Forum. Clinical scenarios for
which product switching may be cause for concern were discussed; when there is a
clinical need, there are no absolute contraindications to switching, but some
patients (e.g. previously untreated patients and those undergoing elective
surgery) may require more careful consideration. Both patient and physician
surveys indicate that the reluctance to switch, and the fear of inhibitor
development, does not appear to be evidence based. The evaluation of more recent
data did not support previous studies suggesting that particular products (e.g.
recombinant vs. plasma-derived and full length vs. B-domain modified) may be
associated with increased risk. In addition, data from three national product
switches showed that switching was not associated with increased inhibitor risk,
but highlighted the need for regular inhibitor testing and for a centralised,
unbiased database of inhibitor incidence. To conclude, current evidence does not
suggest that switching products significantly influences inhibitor development.
PMID- 25135594
TI - Do men need empowering too? A systematic review of entrepreneurial education and
microenterprise development on health disparities among inner-city black male
youth.
AB - Economic strengthening through entrepreneurial and microenterprise development
has been shown to mitigate poverty-based health disparities in developing
countries. Yet, little is known regarding the impact of similar approaches on
disadvantaged U.S. populations, particularly inner-city African-American male
youth disproportionately affected by poverty, unemployment, and adverse health
outcomes. A systematic literature review was conducted to guide programming and
research in this area. Eligible studies were those published in English from 2003
to 2014 which evaluated an entrepreneurial and microenterprise initiative
targeting inner-city youth, aged 15 to 24, and which did not exclude male
participants. Peer-reviewed publications were identified from two electronic
bibliographic databases. A manual search was conducted among web-based gray
literature and registered trials not yet published. Among the 26 papers retrieved
for review, six met the inclusion criteria and were retained for analysis. None
of the 16 registered microenterprise trials were being conducted among
disadvantaged populations in the U.S. The available literature suggests that
entrepreneurial and microenterprise programs can positively impact youth's
economic and psychosocial functioning and result in healthier decision-making.
Young black men specifically benefited from increased autonomy, engagement, and
risk avoidance. However, such programs are vastly underutilized among U.S.
minority youth, and the current evidence is insufficiently descriptive or
rigorous to draw definitive conclusions. Many programs described challenges in
securing adequate resources, recruiting minority male youth, and sustaining
community buy-in. There is an urgent need to increase implementation and
evaluation efforts, using innovative and rigorous designs, to improve the low
status of greater numbers of African-American male youth.
PMID- 25135595
TI - Mycobacterium simiae infection in two unrelated patients with different forms of
inherited IFN-gammaR2 deficiency.
AB - Interferon-gamma receptor 2 (IFN-gammaR2) deficiency is a rare primary
immunodeficiency characterized by predisposition to infections with weakly
virulent mycobacteria, such as environmental mycobacteria and BCG vaccines. We
describe here two children with IFN-gammaR2 deficiency, from unrelated,
consanguineous kindreds of Arab and Israeli descent. The first patient was a boy
who died at the age of 4.5 years, from recurrent, disseminated disease caused by
Mycobacterium simiae. His IFN-gammaR2 defect was autosomal recessive and
complete. The second patient was a girl with multiple disseminated mycobacterial
infections, including infection with M. simiae. She died at the age of 5 years, a
short time after the transplantation of umbilical cord blood cells from an
unrelated donor. Her IFN-gammaR2 defect was autosomal recessive and partial.
Autosomal recessive IFN-gammaR2 deficiency is life-threatening, even in its
partial form, and genetic diagnosis and familial counseling are therefore
particularly important for this condition. These two cases are the first of IFN
gammaR2 deficiency associated with M. simiae infection to be described.
PMID- 25135596
TI - Successful anti-TNF-alpha treatment in a girl with LAD-1 disease and autoimmune
manifestations.
AB - Leukocyte adhesion deficiency type 1 (LAD-1) is an autosomal recessive disorder,
caused by the absence or reduced expression of the beta-2 integrins on
granulocytes, and characterized by the inability of these cells to emigrate from
the bloodstream towards the sites of tissue inflammation. A twelve-year-old girl
with a diagnosis of LAD-1 syndrome and recurrent skin and mucosal infections
since birth, presented with a two week history of fever, abdominal pain,
vomiting, weight loss and polyarthralgia. She underwent an exploratory laparotomy
with the finding of inflamed terminal ileum and colon and a normal appendix.
Colonoscopy and videocapsule endoscopy showed multiple ileal and colonic mucosal
ulcerations, which were compatible with inflammatory bowel disease, confirmed on
histological examination. Given the lack of response to conventional therapy
(prednisone and mesalamine), a monoclonal anti-TNF-alpha antibody was started at
a dosage of 5 mg/kg at weeks 0,2,4,6 and then every 8 weeks. We observed a
significant improvement of all clinical and laboratory parameters after the first
weeks of therapy. Five months later, we anticipated the drug's administration
every 5 weeks because of a precocious recurrence of symptoms. After 30 months of
treatment no relapse nor any relevant side effects have been observed, and
corticosteroids were withdrawn. Interestingly, our patient presented a small
subset of CD18+ T cells, similarly to previously reported LAD-1 patients with
mild phenotype, inflammatory bowel disease and CD18+ somatic revertant T cells.
To the best of our knowledge, this is the first LAD-1 pediatric patient with
inflammatory autoimmune complications who experienced a positive response to anti
TNF-alpha treatment.
PMID- 25135597
TI - Increased prevalence of gastrointestinal viruses and diminished secretory
immunoglobulin a levels in antibody deficiencies.
AB - PURPOSE: Gastrointestinal disease occurs frequently in antibody deficiencies.
This study aims to explore the relation between gastrointestinal infections and
mucosal homeostasis in patients with antibody deficiencies. METHODS: We performed
an observational study including 54 pediatric antibody deficient patients (48 %
CVID, 41 % CVID-like, 11 % XLA) and 66 healthy controls. Clinical symptom scores
and stool samples were collected prospectively. Stool samples were evaluated for
bacteria, parasites, viruses, secretory IgA- and for calprotectin levels. Results
were compared between patients and controls. RESULTS: 24 % of antibody deficient
patients versus 9 % of healthy controls tested positive for gastrointestinal
viruses (p = 0.028). Fecal calprotectin levels were significantly higher in virus
positive patients compared to virus negative patients (p = 0.002). However, in
controls, fecal calprotectin levels were similar between virus positive and virus
negative controls. Moreover, gastrointestinal virus positive patients had low
serum IgA levels in 13/14 cases (94 %) versus 40/62 (62 %) patients in the virus
negative patient group (p = 0.04). The virus positive patient group also
displayed significantly lower secretory IgA levels in stool (median 13 ug/ml)
than patients without gastrointestinal viruses detected or healthy controls
(median 155 ug/ml) (p = 0.046). CONCLUSION: We here report an increased
prevalence of gastrointestinal viruses and gastrointestinal complaints in
antibody deficient patients. Patients that tested positive for gastrointestinal
viruses showed diminished serum- and secretory IgA levels, and only in patients,
virus positivity was associated with signs of mucosal inflammation. These
findings suggest that particularly patients with low IgA are at risk for
longstanding replication of gastrointestinal viruses, which may eventually result
in CVID-related enteropathy.
PMID- 25135598
TI - Sleep and circadian rhythms in hospitalized patients with decompensated
cirrhosis: effect of light therapy.
AB - Patients with liver cirrhosis often exhibit sleep-wake abnormalities, which are,
at least to some extent, circadian in origin. A relatively novel non
pharmacological approach to circadian disruption is appropriately timed bright
light therapy. The aims of this pilot study were to investigate sleep-wake
characteristics of a well-characterized population of inpatients with cirrhosis,
and to evaluate the efficacy of bright light therapy in the hospital setting.
Twelve consecutive inpatients with cirrhosis underwent complete sleep-wake
assessment, to include qualitative and semi-quantitative (actigraphic) indices of
night-time sleep quality, daytime sleepiness, diurnal preference, habitual sleep
timing, quality of life, mood and circadian rhythmicity [i.e. urine collections
for measurement of the melatonin metabolite 6-sulphatoxymelatonin (aMT6s)].
Patients showed extremely impaired night sleep quality (Pittsburg Sleep Quality
Index global score: 16.3 +/- 2.1) and daytime sleepiness was common (Epworth
Sleepiness Scale: 8.3 +/- 3.2). Five patients were randomly assigned to a single
room in which lighting was controlled in relation to timing, spectral composition
and intensity (lights on at 06:30 and off at 22:30, blue-enriched, more intense
light in the morning, red-enriched, less intense light in the afternoon/evening);
the others stayed in identical rooms with standard lighting. Sleep diaries
revealed poor sleep quality, prolonged sleep latency (67 +/- 138 min) and a
reduced sleep efficiency (69 +/- 21%). These features were confirmed by
actigraphy (sleep efficiency: 71 +/- 13%; fragmentation index: 55 +/- 15%).
Quality of life was globally impaired, and mood moderately depressed (Beck
Depression Inventory: 19.4 +/- 7.9). Seven patients underwent serial urine
collections: no circadian aMT6s rhythm was detected in any of them, neither at
baseline, nor during the course of hospitalization in either room (n = 4). In
conclusion, sleep and circadian rhythms in hospitalized, decompensated patients
with cirrhosis are extremely compromised. Treatment with bright light therapy did
not show obvious, beneficial effects, most likely in relation to the severity of
disturbance at baseline.
PMID- 25135599
TI - Behavioral and neurochemical changes induced by repetitive combined treatments of
ketamine and amphetamine in mice.
AB - The combined abuse of recreational drugs such as ketamine (Ket) and amphetamine
(Amph) should be seriously considered important social and health issues.
Numerous studies have documented the behavioral and neurochemical changes
associated with polydrug administration; however, most studies have only examined
the acute effects. The consequences following chronic repetitive polydrug use are
less studied. In the present study, intraperitoneal injections of saline, Amph (5
mg/kg), low dose Ket (LK, 10 mg/kg), high dose Ket (HK, 50 mg/kg), or Amph plus
LK or HK (ALK or AHK) were conducted twice a day for three consecutive days, and
one final treatment was administered on day 4. After seven total treatments,
animal behaviors, including locomotion, stereotypy and ataxia, were examined in a
novel open field. The expression of GAD67 and dopamine (DA) levels were assessed
in the striatum and motor-related cortices using immunohistochemistry and high
performance liquid chromatography. Drug-induced hyperactivities and Amph-mediated
potentiation of Ket-triggered ataxia manifested after repeated drug treatments. A
significant increase in the number of GAD67-positive puncta in the striatum and
motor-related cortices was observed, suggesting a neural adaptive change in the
GABAergic system. Four hours after the final treatment, while the behavioral
hyperactivities had ceased, considerable changes were still evident in the motor
related cortices, suggesting modulation to the DAergic system. Together, our
results show the interactive effects of these two drugs in behavioral and
neurochemical aspects and neural adaptive changes in the GABAergic and DAergic
systems.
PMID- 25135600
TI - CCN1 mutation is associated with atrial septal defect.
AB - The genetic basis of congenital heart disease remains unknown in most of the
cases. Recently, a novel mouse model shed new light on the role of CCN1/CYR61, a
matricellular regulatory factor, in cardiac morphogenesis. In a candidate gene
approach, we analyzed a cohort of 143 patients with atrial septal defects (ASD)
by sequencing the coding exons of CCN1. In addition to three frequent
polymorphisms, we identified an extremely rare novel heterozygous missense
mutation (c.139C > T; p.R47W) in one patient with severe ASD. The mutation leads
to an exchange of residues with quite different properties in a highly conserved
position of the N-terminal insulin-like growth factor binding protein module.
Further bioinformatic analysis, exclusion of known ASD disease genes as well as
the exclusion of the mutation in a very high number of ethnically matched
controls (more than 1,000 individuals) and in public genetic databases, indicates
that the p.R47W variant is a probable disease-associated mutation. The report
about ASD in mice in heterozygous Ccn 1 +/- animals strongly supports this
notion. Our study is the first to suggest a relationship between a probable CCN1
mutation and ASD. Our purpose here was to draw attention to CCN1, a gene that we
believe may be important for genetic analysis in patients with congenital heart
disease.
PMID- 25135601
TI - Incidence, predictors, and outcomes of extubation failure in children after
orthotopic heart transplantation: a single-center experience.
AB - The objective of this study is to describe the incidence, etiologies, predictors,
and outcomes of extubation failure in children undergoing orthotopic heart
transplantation (OHT). A Retrospective, observational study was designed to
evaluate clinical outcomes. . The study was conducted in a cardiovascular
intensive care unit (CVICU) setting at a single, tertiary care, academic
children's hospital. We collected demographic, pre-operative, intra-operative,
post-operative and peri-extubation data in a retrospective, observational format
from patients who underwent OHT at our institution. Clinical outcomes evaluated
included the success or failure of extubation, CVICU length of stay (LOS),
hospital LOS, and in-hospital mortality. We utilized descriptive and univariate
statistics to compare the group with extubation failure to the group with
extubation success. There were no interventions in this study. During the study
period, 127 patients qualified for inclusion. The median age of patients was 108
months [interquartile range (IQR): 25-169] and median weight was 23 kg (IQR: 10.6
48). Extubation failure occurred in 12.5 % (16/127) of the patients. Median
duration of mechanical ventilation was 2 days (IQR: 1-4.5), median CVICU LOS was
7 days (IQR: 5-13), and the median hospital LOS was 36 days (IQR: 20-74). Overall
in-hospital mortality was 2 % (2/127). There was a significant improvement in
blood pressure (p < 0.001) with a decrease in inotropic score (p < 0.001) after
removal of positive pressure ventilation among the patients with extubation
success. Independent factors associated with extubation failure included lower
body weight, need for mechanical ventilation prior to heart transplantation,
renal failure prior to extubation attempt, and right ventricular diastolic
dysfunction prior to extubation attempt. Our study demonstrates that extubation
failure in patients after OHT is infrequent and the causes are diverse.
Extubation success in children after OHT is associated with improvement in mean
arterial blood pressure, decrease in inotropic support, and decrease in
supplemental oxygen requirement.
PMID- 25135602
TI - Impact of prenatal diagnosis in survivors of initial palliation of single
ventricle heart disease: analysis of the National Pediatric Cardiology Quality
Improvement Collaborative database.
AB - Among infants with single ventricle congenital heart disease (SVD) requiring
Stage I palliation (S1P), the impact of prenatal diagnosis (PD) on outcomes has
been variably characterized. We investigated the impact of PD in a large multi
center cohort of survivors of S1P in the National Pediatric Cardiology Quality
Improvement Collaborative (NPCQIC) registry. Retrospective analysis of
demographic and outcomes data among infants enrolled in the NPCQIC database;
eligibility includes SVD requiring S1P and survival to discharge. From 43
contributing surgical centers, 591 infants had data available through time of BDG
(519) or interstage death (55). Median gestational age was 39 weeks (31-46), and
66% had variants of hypoplastic left heart syndrome. PD was made in 445 (75%),
with significant variation by center (p = 0.004). While infants with PD had
slightly lower gestational age at birth (p < 0.001), there were no differences in
birth weight, the presence of major syndromes or other organ system anomalies.
Those without PD were more likely to have atrioventricular valve regurgitation (p
= .002), ventricular dysfunction (p = 0.06), and pre-operative risk factors
including acidosis (p < 0.001), renal insufficiency (p = 0.007), and shock (p =
0.05). Post-operative ventilation was shorter in the PD group (9 vs. 12 d, p =
0.002). Other early post-operative outcomes, interstage course, and outcomes at
BDG were similar between groups. In a large cohort of infants with SVD surviving
to hospital discharge after S1P, PD showed significant inter-site variation and
was associated with improved pre-operative status and shorter duration of
mechanical ventilation. The significance of such associations merits further
study.
PMID- 25135603
TI - Lifetime cardiac reinterventions following the Fontan procedure.
AB - Patients with single ventricle physiology face significant morbidity and
mortality following the Fontan procedure resulting in the need for additional
cardiac reinterventions. Online patient education resources provide limited
information on the reinterventions performed in single ventricle patients
following the Fontan procedure. We sought to determine cardiac surgical and
percutaneous reintervention rates and factors affecting reinterventions following
the Fontan procedure. Databases from a single tertiary care center were
retrospectively reviewed for all patients who underwent a Fontan procedure
between 1978 and 2002. The number and type of cardiac surgical and percutaneous
interventions following the Fontan procedure were determined, and relationships
between need for reintervention and clinical variables were sought. A total of 91
patients (55 males) underwent the Fontan procedure at a median age of 5.50 years
(IQR: 3.33-9.50 years). Median age at last follow-up, death, or transplant was
21.89 years (IQR: 10.87-25.51 years). Following the Fontan procedure, 60 (66%)
patients required an additional 144 median sternotomies and 61 (67%) required 139
percutaneous cardiac interventions. Pacemaker system placement/replacement was
the most common intervention following the Fontan procedure. The median time to
first cardiac surgery following the Fontan was 1.96 years (IQR: 0.06-8.42 years)
while the median time to the first percutaneous intervention was 7.63 years (IQR:
0.65-15.89 years). Families of single ventricle patients should be counseled on
the likelihood of requiring additional cardiac interventions following the Fontan
procedure.
PMID- 25135604
TI - Predicting utility of exercise tests based on history/holter in patients with
premature ventricular contractions.
AB - Premature ventricular contractions (PVCs) are considered benign in patients with
structurally normal hearts, particularly if they suppress with exercise.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) requires exercise
testing to unmask the malignant phenotype. We studied risk factors and Holter
monitor variables to help predict the necessity of exercise testing in patients
with PVCs. We retrospectively reviewed 81 patients with PVCs that suppressed at
peak exercise and structurally normal hearts referred to the exercise laboratory
in 2011. We reviewed 11 patients from 2003 to 2012 whose PVCs were augmented at
peak exercise (mean age 13 +/- 4 years; 52 % male, 180 exercise studies). We
recorded clinical risk factors and comorbidities (family history of arrhythmia or
sudden unexpected death [SUD], presence of syncope) and Holter testing
parameters. Family history of VT or SUD (P = 0.011) and presence of VT on Holter
(P = 0.011) were significant in predicting failure of PVCs to suppress at peak
heart rate on exercise testing. Syncope was not statistically significant in
predicting suppression (P = 0.18); however, CPVT was diagnosed in four patients
with syncope during exercise. Quantity of PVCs, Lown grade, couplets on Holter,
monomorphism, and PVC elimination at peak heart rate on Holter were not
predictors of PVC suppression on exercise testing. Patients with syncope during
exercise, family history of arrhythmia or SUD, or a Holter monitor showing VT
warrant exercise testing to assess for CPVT.
PMID- 25135605
TI - Next-generation sequencing is a credible strategy for blood group genotyping.
AB - Although several medium/high-throughput tools have been engineered for molecular
analysis of blood group genes, they usually rely on the targeting of single
nucleotide polymorphisms, while other variants remain unidentified. To circumvent
this limitation a strategy for genotyping blood group genes by next-generation
sequencing (NGS) was set up. Libraries consisting of exons, flanking introns and
untranslated regions of 18 genes involved in 15 blood systems were generated by
the Ion AmpliSeq(TM) Library Kit 2.0 and by fragmenting polymerase chain reaction
products, normalized by two different approaches, mixed and sequenced by the Ion
Torrent Personal Genome Machine (PGM(TM) ) Sequencer. In our conditions, defined
to limit both intra- and inter-sample variability, sequences from mixed libraries
were read in a single run for a total coverage of 86.03% of the coding DNA
sequences, including all loci defining the most clinically relevant antigens in
all genes, except ABO. Importantly, the challenging attempt to generate gene
specific data for the homologous genes was successful. This work, which combines
two complementary approaches to generate libraries, defines technical conditions
for genotyping blood group genes, illustrates that NGS is suitable for such an
application and suggests that, after automation, this novel tool could be used
for molecular typing at the laboratory level.
PMID- 25135606
TI - Self-powered ion detectors based on dye-sensitized photovoltaics.
AB - Autonomous sensing of metal ion contamination in remote environments with high
reproducibility and sensitivity could unlock many new applications, but involves
trade-offs between compactness, sensitivity, and power provisioning. In prior
demonstrations of semi-autonomous sensors, the power source (e.g. a solar cell)
was an additional component. Here, we demonstrate a concept, wherein a dye
sensitized solar cell is used for both power generation and sensitive detection
of ionic analytes, unlocking a new pathway for ultra-miniaturization and
integration.
PMID- 25135607
TI - Ovulation and extra-ovarian origin of ovarian cancer.
AB - The mortality rate of ovarian cancer remains high due to late diagnosis and
recurrence. A fundamental step toward improving detection and treatment of this
lethal disease is to understand its origin. A growing number of studies have
revealed that ovarian cancer can develop from multiple extra-ovarian origins,
including fallopian tube, gastrointestinal tract, cervix and endometriosis.
However, the mechanism leading to their ovarian localization is not understood.
We utilized in vitro, ex vivo, and in vivo models to recapitulate the process of
extra-ovarian malignant cells migrating to the ovaries and forming tumors. We
provided experimental evidence to support that ovulation, by disrupting the
ovarian surface epithelium and releasing chemokines/cytokines, promotes the
migration and adhesion of malignant cells to the ovary. We identified the
granulosa cell-secreted SDF-1 as a main chemoattractant that recruits malignant
cells towards the ovary. Our findings revealed a potential molecular mechanism of
how the extra-ovarian cells can be attracted by the ovary, migrate to and form
tumors in the ovary. Our data also supports the association between increased
ovulation and the risk of ovarian cancer. Understanding this association will
lead us to the development of more specific markers for early detection and
better prevention strategies.
PMID- 25135608
TI - Screening carbohydrate libraries for protein interactions using the direct ESI-MS
assay. Applications to libraries of unknown concentration.
AB - A semiquantitative electrospray ionization mass spectrometry (ESI-MS) binding
assay suitable for analyzing mixtures of oligosaccharides, at unknown
concentrations, for interactions with target proteins is described. The assay
relies on the differences in the ratio of the relative abundances of the ligand
bound and free protein ions measured by ESI-MS at two or more initial protein
concentrations to distinguish low affinity (<=10(3) M(-1)) ligands from moderate
and high affinity (>10(5) M(-1)) ligands present in the library and to rank their
affinities. Control experiments were performed on solutions of a single chain
antibody and a mixture of synthetic oligosaccharides, with known affinities, in
the absence and presence of a 40-component carbohydrate library to demonstrate
the implementation and reliability of the assay. The application of the assay for
screening natural libraries of carbohydrates against proteins is also
demonstrated using mixtures of human milk oligosaccharides, isolated from breast
milk, and fragments of a bacterial toxin and human galectin 3.
PMID- 25135611
TI - Degradation mechanism of sulfonated poly(ether ether ketone) (SPEEK) ion exchange
membranes under vanadium flow battery medium.
AB - The degradation mechanism of hydrocarbon ion exchange membranes under vanadium
flow battery (VFB) medium was investigated and clarified for the first time. This
work will be highly beneficial for improving the chemical stability of
hydrocarbon ion exchange membranes, which is one of the most challenging issues
for VFB application.
PMID- 25135609
TI - What protein charging (and supercharging) reveal about the mechanism of
electrospray ionization.
AB - Understanding the charging mechanism of electrospray ionization is central to
overcoming shortcomings such as ion suppression or limited dynamic range, and
explaining phenomena such as supercharging. Towards that end, we explore what
accumulated observations reveal about the mechanism of electrospray. We introduce
the idea of an intermediate region for electrospray ionization (and other
ionization methods) to account for the facts that solution charge state
distributions (CSDs) do not correlate with those observed by ESI-MS (the latter
bear more charge) and that gas phase reactions can reduce, but not increase, the
extent of charging. This region incorporates properties (e.g., basicities)
intermediate between solution and gas phase. Assuming that droplet species
polarize within the high electric field leads to equations describing ion
emission resembling those from the equilibrium partitioning model. The equations
predict many trends successfully, including CSD shifts to higher m/z for
concentrated analytes and shifts to lower m/z for sprays employing smaller
emitter opening diameters. From this view, a single mechanism can be formulated
to explain how reagents that promote analyte charging ("supercharging") such as m
NBA, sulfolane, and 3-nitrobenzonitrile increase analyte charge from "denaturing"
and "native" solvent systems. It is suggested that additives' Bronsted basicities
are inversely correlated to their ability to shift CSDs to lower m/z in positive
ESI, as are Bronsted acidities for negative ESI. Because supercharging agents
reduce an analyte's solution ionization, excess spray charge is bestowed on
evaporating ions carrying fewer opposing charges. Bronsted basicity (or acidity)
determines how much ESI charge is lost to the agent (unavailable to evaporating
analyte).
PMID- 25135610
TI - Peptide scrambling during collision-induced dissociation is influenced by N
terminal residue basicity.
AB - 'Bottom up' proteomic studies typically use tandem mass spectrometry data to
infer peptide ion sequence, enabling identification of the protein whence they
derive. The majority of such studies employ collision-induced dissociation (CID)
to induce fragmentation of the peptide structure giving diagnostic b-, y-, and a-
ions. Recently, rearrangement processes that result in scrambling of the original
peptide sequence during CID have been reported for these ions. Such processes
have the potential to adversely affect ion accounting (and thus scores from
automated search algorithms) in tandem mass spectra, and in extreme cases could
lead to false peptide identification. Here, analysis of peptide species produced
by Lys-N proteolysis of standard proteins is performed and sequences that exhibit
such rearrangement processes identified. The effect of increasing the gas-phase
basicity of the N-terminal lysine residue through derivatization to homoarginine
toward such sequence scrambling is then assessed. The presence of a highly basic
homoarginine (or arginine) residue at the N-terminus is found to disfavor/inhibit
sequence scrambling with a coincident increase in the formation of b(n-1)+H(2)O
product ions. Finally, further analysis of a sequence produced by Lys-C
proteolysis provides evidence toward a potential mechanism for the apparent
inhibition of sequence scrambling during resonance excitation CID.
PMID- 25135612
TI - Assessment of motor and process skills in daily life activities of treated
substance addicts.
AB - AIM: The purpose of this study was to apply the Assessment of Motor and Process
Skills (AMPS) in a sample of people in treatment for addictive behaviours and to
study the results. METHODS: The test was applied to a sample of 101 outpatients
in treatment for addiction to substances. The results were studied in relation to
gender, age, level of education, and variables related to addiction. RESULTS:
Motor and cognitive performance was negatively related to time of addiction and
its severity. Sixty per cent of the sample reached suboptimal scores and 25%
showed scores suggesting significant deterioration, especially with regard to
cognitive processing skills. CONCLUSIONS: The AMPS seems to be a useful
instrument to estimate the cognitive and motor impairment associated with
addiction in daily life activities. The present work is the first to consider its
applicability to drug users under treatment. The percentage of subjects affected
and the magnitude of the observed impairment in the sample suggest the need to
consider taking these deficits into account in treatment programmes and the
convenience of incorporating functional rehabilitation as a basic element of the
treatment of persons with addictions. Future studies should develop this
instrument in larger samples, increasing the representativeness and
generalizability of the results.
PMID- 25135614
TI - Seasonal variation in the presentation of thyroid cancer in the USA: an analysis
of the Surveillance, Epidemiology and End Results Registry.
PMID- 25135613
TI - A binuclear Zn(II)-Zn(II) complex from a 2-hydroxybenzohydrazide-derived Schiff
base for selective detection of pyrophosphate.
AB - A hydroxybenzohydrazide-based Schiff base ligand was conveniently synthesized.
Upon addition of Zn(2+) cations, the ligand exhibited a high tendency to form a
binuclear structure with a 2 : 2 ligand-to-zinc ratio, which was accompanied by a
large fluorescence turn-on (lambdaem = 507 nm, phifl~ 0.28). The reactivity of
the zinc complex was examined using different phosphate anions, which reveals a
higher response to acid pyrophosphate anions. Detailed spectroscopic studies show
that the pyrophosphate response is based on the ligand displacement mechanism.
PMID- 25135615
TI - Long-term use of 5alpha-reductase inhibitors and the risk of male breast cancer.
AB - BACKGROUND: The 5alpha-reductase inhibitors (5-ARI) finasteride and dutasteride
are indicated for the treatment of lower urinary tract symptoms caused by benign
prostatic hyperplasia. Case reports have suggested that 5-ARIs increase the risk
for male breast cancer, with no conclusive evidence. The objective of this study
was to quantify the association between use of 5-ARIs and the risk for male
breast cancer. METHODS: A case-control study was conducted with data from the
United Kingdom Clinical Practice Research Datalink database among all men aged 45
years and older in the period 1 January 1992 to 31 December 2011. Cases of men
diagnosed with breast cancer were matched to up 10 controls on age and general
practice. Crude and adjusted odds ratios were estimated for the risk of breast
cancer associated with the use of 5-ARIs. RESULTS: Three hundred and ninety-eight
cases were identified and matched to 3,930 controls. Ever use of 5-ARIs was
associated with an adjusted odds ratio for breast cancer of 1.08 (95 % CI 0.62
1.87) compared to non-users. Increasing cumulative duration of treatment showed
no increasing risks: adjusted odds ratios for use for less than 280, for 280 to
1,036 and for more than 1,036 days were 1.21 (95 % CI 0.47-3.10), 0.94 (95 % CI
0.36-2.41) and 1.29 (95 % CI 0.54-3.08), respectively. CONCLUSIONS: In this
study, there was no evidence of an association between short- or long-term
treatment with 5-ARIs and the risk for breast cancer in older men.
PMID- 25135616
TI - The presence of clustered circulating tumor cells (CTCs) and circulating
cytokines define an aggressive phenotype in metastatic colorectal cancer.
AB - PURPOSE: Colon carcinoma is a malignant tumor showing a marked preference to
metastasize to distant organs. The presence of circulating tumor cells (CTCs) in
the peripheral blood is a prerequisite for the formation of distant metastases.
However, whether circulating cytokines are linked to the circulation of tumor
cells, as individual cells or clusters, remain unclear. In this study, we
investigated the circulating levels of TGF-beta, CXCL1, VEGF and PAI-1 as
potential bioindicators of the presence of CTCs in patients with metastatic colon
cancer. METHODS: Circulating tumor cells (CTCs) were isolated from peripheral
blood by immunomagnetic separation and phenotypically characterized in a cohort
of 103 patients with metastatic colon cancer. TGF-beta, CXCL1, VEGF and PAI-1
concentrations were determined by immunoassay in plasma samples from the same
patients. RESULTS: We detected two different populations of CTCs, single cells or
clusters in patients with metastatic colon cancer. Importantly, we found that the
presence of clustered CTCs is significantly associated with elevated circulating
levels of TGF-beta and CXCL1 and with reduced overall survival. Finally, we
observed that circulating levels of cytokines are differently associated with the
two populations of CTCs. CONCLUSIONS: Taken together, these findings show that
detection of clustered CTCs represents a negative prognostic factor in patients
with metastatic colon cancer. The presence of clustered CTCs is associated with
elevated circulating levels of cytokines such as TGF-beta and CXCL1. This
suggests an additional role for circulating cytokines as predictive tool for
cancer prognosis and diagnosis of minimal residual disease as well as assessment
of tumor sensitivity to anticancer therapy.
PMID- 25135618
TI - Indications, technique, and outcome of therapeutic apheresis in European
pediatric nephrology units.
AB - BACKGROUND: Few observations on apheresis in pediatric nephrology units have been
published. METHODS: This retrospective study involved children <=18 years
undergoing plasma exchange (PE), immunoadsorption (IA), or double filtration
plasmapheresis (DFPP) in 12 European pediatric nephrology units during 2012.
RESULTS: Sixty-seven children underwent PE, ten IA, and three DFPP, for a total
of 738 PE and 349 IA/DFPP sessions; 67.2 % of PE and 69.2 % of IA/DFPP patients
were treated for renal diseases, in particular focal segmental glomerulosclerosis
(FSGS), hemolytic-uremic syndrome (HUS), and human leukocyte antigen (HLA)
desensitization prior to renal transplantation; 20.9 % of PE and 23.1 % of
IA/DFPP patients had neurological diseases. Membrane filtration was the most
common technique, albumin the most frequently used substitution fluid, and
heparin the preferred anticoagulant. PE achieved full disease remission in 25
patients (37.3 %), partial remission in 22 (32.8 %), and had no effect in 20
(29.9 %). The response to IA/DFPP was complete in seven patients (53.8 %),
partial in five (38.5 %), and absent in one (7.7 %). Minor adverse events
occurred during 6.9 % of PE and 9.7 % of IA/DFPP sessions. CONCLUSIONS: PE, IA,
and DFPP are safe apheresis methods in children. Efficacy is high in pediatric
patients with recurrent focal segmental glomerulosclerosis (FSGS), atypical
hemolytic uremic syndrome (HUS), human leukocyte antigen (HLA) sensitization, and
neurological autoimmune diseases.
PMID- 25135620
TI - Crystal lattice effect on the quenching of the intracluster magnetic interaction
in [V12B18O60H6](10-) polyoxometalate.
AB - In the present work, the synthesis and structural characterization of four new
polyoxovanadoborate (BVO) frameworks based on the [V12B18O60H6](10-) polyanion
are reported: (NH4)8(1,3-diapH2)[V12B18O60H6].5H2O (1),
K8(NH4)2[V12B18O60H6].18H2O (2), K10[V12B18O60H6].10H2O (3) and
K8Cs2[V12B18O60H6].10H2O (4). A global antiferromagnetic behaviour is observed
for these 10V(IV)/2V(V) mixed valence clusters. The magnetic data of 1, 2 and 3,
which present different countercation environments, show that 1 is more coupled
than 2 and 3. DFT calculations show that the positive charges strongly influence
the polarization mechanism of the spin density of the vanadyl groups and the
extent of the magnetic orbitals, therefore corroborating the experimental
observation of the quenching effect of the magnetic coupling between vanadium
centres of 2 and 3.
PMID- 25135619
TI - Can vitamin D status be assessed by serum 25OHD in children?
AB - BACKGROUND: To examine the relationship of serum 25-hydroxyvitamin D (25OHD)
concentrations with serum parathyroid hormone (PTH) levels, body mass index
(BMI), and environmental factors in a population of Caucasian children living at
latitude 43 degrees N. METHODS: Cross-sectional study on 288 children aged 1
month to 13 years who presented to a pediatric emergency unit during a 21-month
period. RESULTS: Mean (SD) serum 25OHD concentrations were 40.6 (17.6), 30.9
(12.0), and 26.4 (9.9) ng/ml (1 ng/ml = 2.5 nmol/l), in children aged 0-1, 2-5,
and >= 6 years, respectively. Serum PTH levels were 26.6 (13.6), 24.3 (11.9), and
32.7 (12.1) pg/ml in the same groups. Infants had 25OHD concentrations
significantly higher. PTH levels were significantly higher in children aged >= 6
years. There was no significant correlation between serum 25OHD and PTH
concentrations. Totals of 15.6 % and 2.1 % of children had 25OHD values less than
20 and 10 ng/ml, respectively, but none had elevated serum PTH or clinical
manifestations related with vitamin D deficiency. Age (inverse correlation) and
season (higher values in summer), but not BMI, sex, and time spent outdoors,
influenced serum 25OHD concentrations. CONCLUSIONS: Our results raise doubt on
the assumption of only a serum 25OHD threshold as indicative of vitamin D
deficiency in children.
PMID- 25135617
TI - Cardiac CT for myocardial ischaemia detection and characterization--comparative
analysis.
AB - The assessment of patients presenting with symptoms of myocardial ischaemia
remains one of the most common and challenging clinical scenarios faced by
physicians. Current imaging modalities are capable of three-dimensional,
functional and anatomical views of the heart and as such offer a unique
contribution to understanding and managing the pathology involved. Evidence has
accumulated that visual anatomical coronary evaluation does not adequately
predict haemodynamic relevance and should be complemented by physiological
evaluation, highlighting the importance of functional assessment. Technical
advances in CT technology over the past decade have progressively moved cardiac
CT imaging into the clinical workflow. In addition to anatomical evaluation,
cardiac CT is capable of providing myocardial perfusion parameters. A variety of
CT techniques can be used to assess the myocardial perfusion. The single energy
first-pass CT and dual energy first-pass CT allow static assessment of myocardial
blood pool. Dynamic cardiac CT imaging allows quantification of myocardial
perfusion through time-resolved attenuation data. CT-based myocardial perfusion
imaging (MPI) is showing promising diagnostic accuracy compared with the current
reference modalities. The aim of this review is to present currently available
myocardial perfusion techniques with a focus on CT imaging in light of recent
clinical investigations. This article provides a comprehensive overview of
currently available CT approaches of static and dynamic MPI and presents the
results of corresponding clinical trials.
PMID- 25135622
TI - Effects of four additive solutions on canine leukoreduced red cell concentrate
quality during storage.
AB - BACKGROUND: Additive solutions (AS) and prestorage leukoreduction (LR) are
important tools used to maintain erythrocyte viability during storage and avoid
transfusion reactions in recipients, respectively. OBJECTIVES: The purpose of the
study was to determine the efficacy of a WBC filter (Immugard IIIRC) and compare
the effect of 4 AS (phosphate-adenine-glucose-guanosine-gluconate-mannitol
[PAGGGM], saline-adenine-glucose-mannitol [SAGM], Adsol, Optisol) on the in vitro
quality of canine leukoreduced packed RBC units (pRBC) stored for 41 days.
METHODS: Five hundred milliliters of blood were collected from 8 healthy dogs
each into 70 mL of citrate-phosphate-dextrose (CPD) solution, and were
leukoreduced by a polyurethane filter. pRBC of each dog were divided equally into
4 bags containing a different AS. Bags were stored for 41 days at 4 degrees C and
evaluated every 10 days. Variables analyzed included pH, PCV, and% hemolysis, and
lactate, glucose, potassium, sodium, ATP, and 2,3-diphosphoglycerate (2,3-DPG)
concentrations. RESULTS: The LR resulted in residual WBC counts comparable to
human standards. During storage, pH, and glucose, 2,3-DPG, and ATP concentrations
decreased, and hemolysis, and lactate, sodium, and potassium concentrations
increased (P < .05). Significant differences between AS were seen in the glucose
and sodium concentrations, due to the composition of AS. Also, the pH maintained
by PAGGGM at day 21 was significantly higher than that seen with SAGM or Adsol.
CONCLUSIONS: All AS used gave satisfactory results during the first 21 days of
storage based on the degree of hemolysis, and on ATP and 2,3-DPG concentrations.
When compared with day 1 values, significant changes were seen in these variables
by day 31 with all AS.
PMID- 25135621
TI - Critical periods of increased fetal vulnerability to a maternal high fat diet.
AB - BACKGROUND: Fetal adaptations to high fat (HF) diet in utero (IU) that may
predispose to Metabolic Syndrome (MetS) in adulthood include changes in fetal
hepatic gene expression. Studies were performed to determine whether maternal
exposure to HF diet at different stages during pregnancy had different effects on
the fetus, including hepatic gene expression. METHODS: Female wild type mice were
fed either a HF or breeding chow (C) for 2 wks prior to mating. The experimental
groups were composed of embryonic day (e) 18.5 fetuses obtained from WT female
mice that were fed HF (HF, 35.5% fat) or breeding chow (C, 9.5% fat) for 2 wk
before mating until e9.5 of pregnancy (periconception-midpregnancy). At e9.5 dams
were switched to the opposite diet (C-HF or HF-C). RESULTS: Exposure to HF diet
throughout pregnancy reduced maternal weight gain compared to C diet (p < 0.02 HF
vs. C). HF-C dams had significantly decreased adiponectin levels and litter size
when compared to C-HF (p < 0.02 HF-C vs C-HF). Independent of the timing of
exposure to HF, fetal weight and length were significantly decreased when
compared to C diet (HF, C-HF and HF-C vs. C p < 0.02). HF diet during the second
half of pregnancy increased expression of genes in the fetal liver associated
with fetal growth (C-HF vs C p < 0.001), glucose production (C-HF vs C p < 0.04),
oxidative stress and inflammation (C-HF vs C p < 0.01) compared to C diet.
CONCLUSIONS: This model defines that there are critical periods during gestation
in which the fetus is actively shaped by the environment. Early exposure to a HF
diet determines litter size while exposure to HF during the second half of
pregnancy leads to dysregulation of expression of key genes responsible for fetal
growth, hepatic glucose production and oxidative stress. These findings
underscore the importance of future studies designed to clarify how these
critical periods may influence future risk of developing MetS later in life.
PMID- 25135624
TI - MicroRNAs: a new key in lung cancer.
AB - Lung cancer as a malignance has been killing numerous patients around the world
annually, and small cell lung cancer (SCLC) and non-small cell lung cancer
(NSCLC) are the two major types, the later accounting for nearly 80 % of lung
cancer. There are multiple causes for lung cancer, and more researches have been
carried out to prevent, anticipate, and diagnose the cancer. MicroRNAs (miRNAs)
are small non-coding RNA molecules capable of regulating expression of over 50 %
of protein-coding genes. The RNA molecules are stable in tissues and blood, so it
can tend to be a biomarker in anti-lung cancer. Here, this is a review on the
roles of miRNAs for possible ways to prevent lung cancer in clinical trials.
PMID- 25135623
TI - Clinical challenges in targeting anaplastic lymphoma kinase in advanced non-small
cell lung cancer.
AB - The revolution in individualized therapy for patients with advanced non-small
cell lung cancer (NSCLC) has seen the emergence of a number of molecularly
targeted therapies for distinct patient molecular subgroups. Activating
anaplastic lymphoma kinase (ALK)-gene rearrangement has been detected in 3-7 % of
NSCLC cases, and the ALK inhibitor crizotinib is now an approved treatment for
patients with tumors harboring this event. However, resistance to ALK-targeted
therapies is a ubiquitous problem in the management of advanced ALK-positive
NSCLC and can be mediated by secondary kinase mutations or the activation of
compensatory alternative oncogenic drivers. New, more potent ALK inhibitors such
as ceritinib (LDK378), alectinib (CH5424802), and AP26113 are now emerging,
together with an increased knowledge of the molecular basis of resistance. There
is a need to evaluate the optimal clinical application of these new agents,
either as sequential therapies or in combination with other targeted agents, to
combat resistance and prolong survival in patients with ALK-positive NSCLC. The
remarkable clinical activity of ALK inhibitors also emphasizes the importance of
optimal diagnostic testing algorithms, to ensure that all eligible patients
receive these breakthrough therapies.
PMID- 25135628
TI - Photoinduced oxidation of water in the pyridine-water complex: comparison of the
singlet and triplet photochemistries.
AB - It has recently been shown that low-lying dark charge-separated singlet excited
states of npi* and pipi* character exist in the hydrogen-bonded pyridine-water
complex in addition to the familiar npi* and pipi* excited states of the pyridine
chromophore. The former have been shown to promote the transfer of a proton from
water to pyridine, resulting in the pyridinyl-hydroxyl radical pair. In the
present work, the potential-energy surfaces of the triplet excited states of the
pyridine-water complex have been explored with the same ab initio electronic
structure methods (ADC(2), CASPT2). Minimum-energy reaction paths for excited
state H atom transfer, energy surfaces in the vicinity of the barrier for H atom
transfer, as well as multistate surface crossings have been characterized. The
photochemical reaction mechanisms on the singlet and triplet potential-energy
surfaces are compared, and their relevance for photoinduced water oxidation with
the pyridine chromophore are discussed.
PMID- 25135626
TI - Benzoic and sorbic acid in soft drink, milk, ketchup sauce and bread by
dispersive liquid-liquid microextraction coupled with HPLC.
AB - Benzoic acid and sorbic acid are widely used for food preservation. These
preservatives are generally recognised as safe. The aim of this study was to
determine the level of benzoic and sorbic acid in food samples that are usually
consumed in Iran. Therefore, 54 samples, including 15 soft drinks, 15 ultra-high
temperature milk, 15 ketchup sauces and 9 bread samples, were analysed by high
performance liquid chromatography with UV detection. Benzoic acid was detected in
50 (92.5%) of the samples ranging from 3.5 to 1520 ug mL-1, while sorbic acid was
detected in 29 (50.3%) samples in a range of 0.8 and 2305 ug mL-1. Limits of
detection and limits of quantification for benzoate were found to be 0.1 and 0.5
ug mL-1, respectively, and for sorbate 0.08 and 0.3 ug mL-1, respectively. The
results showed that benzoic acid and sorbic acid widely occur in food products in
Iran.
PMID- 25135629
TI - Adaptive processes drive ecomorphological convergent evolution in antwrens
(Thamnophilidae).
AB - Phylogenetic niche conservatism (PNC) and convergence are contrasting
evolutionary patterns that describe phenotypic similarity across independent
lineages. Assessing whether and how adaptive processes give origin to these
patterns represent a fundamental step toward understanding phenotypic evolution.
Phylogenetic model-based approaches offer the opportunity not only to distinguish
between PNC and convergence, but also to determine the extent that adaptive
processes explain phenotypic similarity. The Myrmotherula complex in the
Neotropical family Thamnophilidae is a polyphyletic group of sexually dimorphic
small insectivorous forest birds that are relatively homogeneous in size and
shape. Here, we integrate a comprehensive species-level molecular phylogeny of
the Myrmotherula complex with morphometric and ecological data within a
comparative framework to test whether phenotypic similarity is described by a
pattern of PNC or convergence, and to identify evolutionary mechanisms underlying
body size and shape evolution. We show that antwrens in the Myrmotherula complex
represent distantly related clades that exhibit adaptive convergent evolution in
body size and divergent evolution in body shape. Phenotypic similarity in the
group is primarily driven by their tendency to converge toward smaller body
sizes. Differences in body size and shape across lineages are associated to
ecological and behavioral factors.
PMID- 25135630
TI - Low-risk transfusion-related acute lung injury donor strategies and the impact on
the onset of transfusion-related acute lung injury: a meta-analysis.
AB - BACKGROUND: Transfusion-related acute lung injury (TRALI) is the leading cause of
transfusion-related mortality. In the past decade blood banks have implemented
low-risk TRALI donor strategies, including a male-only donor policy for plasma
containing blood products to prevent onset of TRALI. We performed a meta-analysis
to determine whether use of low-risk TRALI donor strategies for plasma indeed
reduces onset of TRALI. STUDY DESIGN AND METHODS: We searched MEDLINE and
Cochrane Central Register of Controlled Trials from January 1995 up to January
2013. Two reviewers independently extracted data on study characteristics,
methods, and outcomes. Primary endpoint was onset of TRALI. Subgroup analyses
were performed for patient populations prone to develop TRALI and general patient
populations. RESULTS: Ten articles were included. Meta-analysis using a random
effects model taking into account all transfused products showed a significant
reduction for the risk of TRALI after implementation of low-risk TRALI donor
strategies (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.42-0.88). Data
from patient populations prone to develop TRALI showed a significant reduction of
TRALI risk (OR, 0.51; 95% CI, 0.29-0.90), while data from general patient
populations showed a similar nonsignificant trend (OR, 0.66; 95% CI, 0.40-1.09).
Results were similar when taking only plasma products into account (OR, 0.62; 95%
CI, 0.42-0.92). CONCLUSION: The introduction of low-risk TRALI donor strategies
for plasma-containing products results in a reduction of TRALI.
PMID- 25135631
TI - Sodium tanshinone IIA sulfonate attenuates radiation-induced fibrosis damage in
cardiac fibroblasts.
AB - The main pathological change in radiation-induced heart disease is fibrosis.
Emerging evidence has indicated that sodium tanshinone IIA sulfonate (STS) was
used for treating fibrosis diseases. The present study was undertaken to
characterize the effect of STS on radiation-induced cardiac fibrosis (RICF) on
cultured cardiac fibroblasts (CFs). CFs were irradiated with 1 or 2 Gy X-rays,
and the expression of TGF-beta1 and collagen I (Col-1) increased, indicating that
low-dose X-rays promoted fibrosis damage effect. The fibrosis damage was
accompanied by morphologic changes in the endoplasmic reticulum (ER), as well as
an increase in the expression of the ER stress-related molecules, GRP78 and CHOP.
Administration of STS reduced ROS production and decreased the expression of Col
1, TGF-beta1, p-Smad2/3, GRP78, and CHOP in irradiated CFs, thus weakening the
radiation-induced fibrosis damage and ER stress. Radiation-induced fibrosis
damage was observed on a cellular level. The involvement of ER stress in
radiation-induced fibrosis damage was demonstrated for the first time. STS
attenuated the fibrosis damage effect in CFs and this effect may be related to
its antioxidant action, and also related to its inhibition of ER stress and TGF
beta1-Smad pathway. These results suggest that STS shows a good prospect in
clinical prevention and treatment of RICF.
PMID- 25135627
TI - Dendritic cell subsets require cis-activation for cytotoxic CD8 T-cell induction.
AB - Dendritic cells (DCs) are required for the induction of cytotoxic T cells (CTL).
In most tissues, including the lung, the resident DCs fall into two types
expressing the integrin markers CD103 and CD11b. The current supposition is that
DC function is predetermined by lineage, designating the CD103(+) DC as the major
cross-presenting DC able to induce CTL. Here we show that Poly I:C (TLR3 agonist)
or R848 (TLR7 agonist) do not activate all endogenous DCs. CD11b(+) DCs can
orchestrate a CTL response in vivo in the presence of a TLR7 agonist but not a
TLR3 agonist, whereas CD103(+) DCs require ligation of TLR3 for this purpose.
This selectivity does not extend to antigen cross-presentation for T-cell
proliferation but is required for induction of cytotoxicity. Thus, we demonstrate
that the ability of DCs to induce functional CTLs is specific to the nature of
the pathogen-associated molecular pattern (PAMP) encountered by endogenous DC.
PMID- 25135632
TI - ApiCOWplexa 2013--2nd International Meeting on Apicomplexan Parasites in Farm
Animals.
PMID- 25135633
TI - Elevated dopamine in the medial prefrontal cortex suppresses cocaine seeking via
D1 receptor overstimulation.
AB - Previous investigations indicate that the dopamine-beta-hydroxylase (DBH)
inhibitors disulfiram and nepicastat suppress cocaine-primed reinstatement of
cocaine self-administration behaviour. Moreover, both inhibitors increase
dopamine release in the rat medial prefrontal cortex (mPFC) and markedly
potentiate cocaine-induced dopamine release in this region. This study was aimed
to clarify if the suppressant effect of DBH inhibitors on cocaine reinstatement
was mediated by the high extracellular dopamine in the rat mPFC leading to a
supra-maximal stimulation of D1 receptors in the dorsal division of mPFC, an area
critical for reinstatement of cocaine-seeking behaviour. In line with previous
microdialysis studies in drug-naive animals, both DBH inhibitors potentiated
cocaine-induced dopamine release in the mPFC, in the same animals in which they
also suppressed reinstatement of cocaine seeking. Similar to the DBH inhibitors,
L-DOPA potentiated cocaine-induced dopamine release in the mPFC and suppressed
cocaine-induced reinstatement of cocaine-seeking behaviour. The bilateral
microinfusion of the D1 receptor antagonist SCH 23390 into the dorsal mPFC not
only prevented cocaine-induced reinstatement of cocaine seeking but also reverted
both disulfiram- and L-DOPA-induced suppression of reinstatement. Moreover, the
bilateral microinfusion of the D1 receptor agonist chloro-APB (SKF 82958) into
the dorsal mPFC markedly attenuated cocaine-induced reinstatement of cocaine
seeking. These results suggest that stimulation of D1 receptors in the dorsal
mPFC plays a crucial role in cocaine-induced reinstatement of cocaine seeking,
whereas the suppressant effect of DBH inhibitors and L-DOPA on drug-induced
reinstatement is mediated by a supra-maximal stimulation of D1 receptors leading
to their inactivation.
PMID- 25135634
TI - Japanese guidelines of the management of hematuria 2013.
PMID- 25135635
TI - Blood pressure control and satisfaction of hypertensive patients following a
switch to combined drugs of an angiotensin receptor blocker and a calcium channel
blocker in clinical practice of nephrology.
AB - BACKGROUND: Combination drugs containing an angiotensin receptor blocker and a
calcium channel blocker have been widely commercialized in recent years, and
their advantages, such as improvements in adherence, and reductions in medication
costs, have been greatly emphasized. However, the actual situations and the
impact of switching to combination drugs in clinical practice of nephrology are
not fully understood. METHODS: This study was conducted in outpatients of
nephrology who received antihypertensive medicines, and who switched to
combination drugs. Changes in the potency of the antihypertensive drugs, and
blood pressure were examined retrospectively before and after changing
treatments. In addition, the study also involved patients' questionnaire, which
examined changes in blood pressure at home, the presence or absence of missed
doses, the impact on medication-related expenses, and the level of patients'
satisfaction with regard to combination drugs. RESULTS: Survey results from 90
participants revealed that changing to combination drugs resulted in a reduction
of missed doses, a decrease in blood pressure measured in an outpatient setting,
and a reduction in medication-related expenses in total patients, non-chronic
kidney disease (CKD) patients, and CKD patients. CONCLUSION: Our study shows that
switching to combination antihypertensive drugs resulted in an improvement in
adherence and a reduction in medication-related expenses, and revealed that
patient satisfaction was high. Combination drugs for hypertensive patients may be
beneficial in both medical and economical viewpoints.
PMID- 25135636
TI - Evolutionarily conserved roles of the dicer helicase domain in regulating RNA
interference processing.
AB - The enzyme Dicer generates 21-25 nucleotide RNAs that target specific mRNAs for
silencing during RNA interference and related pathways. Although their active
sites and RNA binding regions are functionally conserved, the helicase domains
have distinct activities in the context of different Dicer enzymes. To examine
the evolutionary origins of Dicer helicase functions, we investigated two related
Dicer enzymes from the thermophilic fungus Sporotrichum thermophile. RNA cleavage
assays showed that S. thermophile Dicer-1 (StDicer-1) can process hairpin
precursor microRNAs, whereas StDicer-2 can only cleave linear double-stranded
RNAs. Furthermore, only StDicer-2 possesses robust ATP hydrolytic activity in the
presence of double-stranded RNA. Deletion of the StDicer-2 helicase domain
increases both StDicer-2 cleavage activity and affinity for hairpin RNA. Notably,
both StDicer-1 and StDicer-2 could complement the distantly related yeast
Schizosaccharomyces pombe lacking its endogenous Dicer gene but only in their
full-length forms, underscoring the importance of the helicase domain. These
results suggest an in vivo regulatory function for the helicase domain that may
be conserved from fungi to humans.
PMID- 25135638
TI - Irreversible heavy chain transfer to chondroitin.
AB - We have recently demonstrated that the transfer of heavy chains (HCs) from inter
alpha-inhibitor, via the enzyme TSG-6 (tumor necrosis factor-stimulated gene 6),
to hyaluronan (HA) oligosaccharides is an irreversible event in which subsequent
swapping of HCs between HA molecules does not occur. We now describe our results
of HC transfer experiments to chondroitin sulfate A, chemically desulfated
chondroitin, chemoenzymatically synthesized chondroitin, unsulfated heparosan,
heparan sulfate, and alginate. Of these potential HC acceptors, only chemically
desulfated chondroitin and chemoenzymatically synthesized chondroitin were HC
acceptors. The kinetics of HC transfer to chondroitin was similar to HA. At
earlier time points, HCs were more widely distributed among the different sizes
of chondroitin chains. As time progressed, the HCs migrated to lower molecular
weight chains of chondroitin. Our interpretation is that TSG-6 swaps the HCs from
the larger, reversible sites on chondroitin chains, which function as HC
acceptors, onto smaller chondroitin chains, which function as irreversible HC
acceptors. HCs transferred to smaller chondroitin chains were unable to be
swapped off the smaller chondroitin chains and transferred to HA. HCs transferred
to high molecular weight HA were unable to be swapped onto chondroitin. We also
present data that although chondroitin was a HC acceptor, HA was the preferred
acceptor when chondroitin and HA were in the same reaction mixture.
PMID- 25135637
TI - The cellular redox environment alters antigen presentation.
AB - Cysteine-containing peptides represent an important class of T cell epitopes, yet
their prevalence remains underestimated. We have established and interrogated a
database of around 70,000 naturally processed MHC-bound peptides and demonstrate
that cysteine-containing peptides are presented on the surface of cells in an MHC
allomorph-dependent manner and comprise on average 5-10% of the immunopeptidome.
A significant proportion of these peptides are oxidatively modified, most
commonly through covalent linkage with the antioxidant glutathione. Unlike some
of the previously reported cysteine-based modifications, this represents a true
physiological alteration of cysteine residues. Furthermore, our results suggest
that alterations in the cellular redox state induced by viral infection are
communicated to the immune system through the presentation of S-glutathionylated
viral peptides, resulting in altered T cell recognition. Our data provide a
structural basis for how the glutathione modification alters recognition by virus
specific T cells. Collectively, these results suggest that oxidative stress
represents a mechanism for modulating the virus-specific T cell response.
PMID- 25135639
TI - Interaction of platelet endothelial cell adhesion molecule (PECAM) with alpha2,6
sialylated glycan regulates its cell surface residency and anti-apoptotic role.
AB - The luminal sides of vascular endothelial cells are heavily covered with a so
called glycocalyx, but the precise role of the endothelial glycocalyx remains
unclear. Our previous study showed that N-glycan alpha2,6-sialylation regulates
the cell surface residency of an anti-apoptotic molecule, platelet endothelial
cell adhesion molecule (PECAM), as well as the sensitivity of endothelial cells
toward apoptotic stimuli. As PECAM itself was shown to be modified with
biantennary N-glycans having alpha2,6-sialic acid, we expected that PECAM would
possess lectin-like activity toward alpha2,6-sialic acid to ensure its homophilic
interaction. To verify this, a series of oligosaccharides were initially added to
observe their inhibitory effects on the homophilic PECAM interaction in vitro. We
found that a longer alpha2,6-sialylated oligosaccharide exhibited strong
inhibitory activity. Furthermore, we found that a cluster-type alpha2,6-sialyl N
glycan probe specifically bound to PECAM-immobilized beads. Moreover, the
addition of the alpha2,6-sialylated oligosaccharide to endothelial cells enhanced
the internalization of PECAM as well as the sensitivity to apoptotic stimuli.
Collectively, these findings suggest that PECAM is a sialic acid binding lectin
and that this binding property supports endothelial cell survival. Notably, our
findings that alpha2,6-sialylated glycans influenced the susceptibility to
endothelial cell apoptosis shed light on the possibility of using a glycan-based
method to modulate angiogenesis.
PMID- 25135641
TI - Glycomic characterization of respiratory tract tissues of ferrets: implications
for its use in influenza virus infection studies.
AB - The initial recognition between influenza virus and the host cell is mediated by
interactions between the viral surface protein hemagglutinin and sialic acid
terminated glycoconjugates on the host cell surface. The sialic acid residues can
be linked to the adjacent monosaccharide by alpha2-3- or alpha2-6-type glycosidic
bonds. It is this linkage difference that primarily defines the species barrier
of the influenza virus infection with alpha2-3 binding being associated with
avian influenza viruses and alpha2-6 binding being associated with human strains.
The ferret has been extensively used as an animal model to study the transmission
of influenza. To better understand the validity of this model system, we
undertook glycomic characterization of respiratory tissues of ferret, which
allows a comparison of potential viral receptors to be made between humans and
ferrets. To complement the structural analysis, lectin staining experiments were
performed to characterize the regional distributions of glycans along the
respiratory tract of ferrets. Finally, the binding between the glycans identified
and the hemagglutinins of different strains of influenza viruses was assessed by
glycan array experiments. Our data indicated that the respiratory tissues of
ferret heterogeneously express both alpha2-3- and alpha2-6-linked sialic acids.
However, the respiratory tissues of ferret also expressed the Sda epitope
(NeuAcalpha2-3(GalNAcbeta1-4)Galbeta1-4GlcNAc) and sialylated N,N'
diacetyllactosamine (NeuAcalpha2-6GalNAcbeta1-4GlcNAc), which have not been
observed in the human respiratory tract surface epithelium. The presence of the
Sda epitope reduces potential binding sites for avian viruses and thus may have
implications for the usefulness of the ferret in the study of influenza virus
infection.
PMID- 25135640
TI - Structural maintenance of chromosome (SMC) proteins link microtubule stability to
genome integrity.
AB - Structural maintenance of chromosome (SMC) proteins are key organizers of
chromosome architecture and are essential for genome integrity. They act by
binding to chromatin and connecting distinct parts of chromosomes together.
Interestingly, their potential role in providing connections between chromatin
and the mitotic spindle has not been explored. Here, we show that yeast SMC
proteins bind directly to microtubules and can provide a functional link between
microtubules and DNA. We mapped the microtubule-binding region of Smc5 and
generated a mutant with impaired microtubule binding activity. This mutant is
viable in yeast but exhibited a cold-specific conditional lethality associated
with mitotic arrest, aberrant spindle structures, and chromosome segregation
defects. In an in vitro reconstitution assay, this Smc5 mutant also showed a
compromised ability to protect microtubules from cold-induced depolymerization.
Collectively, these findings demonstrate that SMC proteins can bind to and
stabilize microtubules and that SMC-microtubule interactions are essential to
establish a robust system to maintain genome integrity.
PMID- 25135642
TI - Molecular characterization of arylsulfatase G: expression, processing,
glycosylation, transport, and activity.
AB - Arylsulfatase G (ARSG) is a recently identified lysosomal sulfatase that was
shown to be responsible for the degradation of 3-O-sulfated N-sulfoglucosamine
residues of heparan sulfate glycosaminoglycans. Deficiency of ARSG leads to a new
type of mucopolysaccharidosis, as described in a mouse model. Here, we provide a
detailed molecular characterization of the endogenous murine enzyme. ARSG is
expressed and proteolytically processed in a tissue-specific manner. The 63-kDa
single-chain precursor protein localizes to pre-lysosomal compartments and
tightly associates with organelle membranes, most likely the endoplasmic
reticulum. In contrast, proteolytically processed ARSG fragments of 34-, 18-, and
10-kDa were found in lysosomal fractions and lost their membrane association. The
processing sites and a disulfide bridge between the 18- and 10-kDa chains could
be roughly mapped. Proteases participating in the processing were identified as
cathepsins B and L. Proteolytic processing is dispensable for hydrolytic
sulfatase activity in vitro. Lysosomal transport of ARSG in the liver is
independent of mannose 6-phosphate, sortilin, and Limp2. However, mutation of
glycosylation site N-497 abrogates transport of ARSG to lysosomes in human
fibrosarcoma cells, due to impaired mannose 6-phosphate modification.
PMID- 25135643
TI - Biochemical characterization of the topoisomerase domain of Methanopyrus kandleri
topoisomerase V.
AB - Topoisomerases are ubiquitous enzymes that modify the topological state of DNA
inside the cell and are essential for several cellular processes. Topoisomerase V
is the sole member of the type IC topoisomerase subtype. The topoisomerase domain
has a unique fold among topoisomerases, and the putative active site residues
show a distinct arrangement. The present study was aimed at identifying the roles
of the putative active site residues in the DNA cleavage/religation process.
Residues Arg-131, Arg-144, His-200, Glu-215, Lys-218, and Tyr-226 were mutated
individually to a series of conservative and non-conservative amino acids, and
the DNA relaxation activity at different pH values, times, and enzyme
concentrations was compared with wild-type activity. The results suggest that Arg
144 is essential for protein stability because any substitution at this position
was deleterious and that Arg-131 and His-200 are involved in transition state
stabilization. Glu-215 reduces the DNA binding ability of topoisomerase V,
especially in shorter fragments with fewer helix-hairpin-helix DNA binding
motifs. Finally, Lys-218 appears to play a direct role in catalysis but not in
charge stabilization of the protein-DNA intermediate complex. The results suggest
that although catalytically important residues are oriented in different fashions
in the active sites of type IB and type IC topoisomerases, similar amino acids
play equivalent roles in both of these subtypes of enzymes, showing convergent
evolution of the catalytic mechanism.
PMID- 25135645
TI - Crystal chemistry and selected physical properties of inorganic fluorides and
oxide-fluorides.
PMID- 25135644
TI - Organizational interplay of Golgi N-glycosyltransferases involves organelle
microenvironment-dependent transitions between enzyme homo- and heteromers.
AB - Glycosylation of proteins and lipids takes place in the Golgi apparatus by the
consecutive actions of functionally distinct glycosidases and
glycosyltransferases. Current evidence indicates that they function as enzyme
homomers and/or heteromers in the living cell. Here we investigate their
organizational interplay and show that glycosyltransferase homomers are assembled
in the endoplasmic reticulum. Upon transport to the Golgi, the majority of
homomers are disassembled to allow the formation of enzyme heteromers between
sequentially acting medial-Golgi enzymes GnT-I and GnT-II or trans-Golgi enzymes
GalT-I and ST6Gal-I. This transition is driven by the acidic Golgi environment,
as it was markedly inhibited by raising Golgi luminal pH with chloroquine. Our
FRAP (fluorescence recovery after photobleaching) measurements showed that the
complexes remain mobile Golgi membrane constituents that can relocate to the
endoplasmic reticulum or to the scattered Golgi mini-stacks upon brefeldin A or
nocodazole treatment, respectively. During this relocation, heteromers undergo a
reverse transition back to enzyme homomers. These data unveil an unprecedented
organizational interplay between Golgi N-glycosyltransferases that involves
dynamic and organelle microenvironment-driven transitions between enzyme homomers
and heteromers during their trafficking within the early secretory compartments.
PMID- 25135646
TI - Frequent cough in unsatisfactory controlled asthma--results from the population
based West Sweden Asthma study.
AB - BACKGROUND: Asthma is a complex disease presenting with variable symptoms which
are sometimes hard to control. The purpose of the study was to describe the
prevalence of asthma symptoms, use of asthma medications and allergic
sensitization in subjects with asthma. We also related those indices to the level
of asthma control, lung function and in particular, cough. METHODS: An extensive
questionnaire was sent to randomly selected adults from the West Sweden region.
Clinical examinations and interview were performed in a subset. Of the
participants, 744 were defined as having an ongoing asthma - reported ever having
asthma or physician diagnosed asthma and one of the following - use of asthma
medications, recurrent wheeze or attacks of shortness of breath with or without
wheeze in the last 12 months. A respiratory disease-free control group of 847
subjects was also described. RESULTS: According to GINA guidelines, 40.6% of the
asthmatics had partly controlled and 17.8% had uncontrolled asthma. Asthmatic
subjects reported significantly more symptoms in the last 12 months than the
control group - wheezing (79.4 vs 9.2%), shortness of breath (36.1 vs 2.5%),
wheezing with shortness of breath (58.7 vs 1.3%). Important complaints were
morning cough (42.5 vs 15.5%), cough with sputum production (36.1 vs 6.8%) and
longstanding cough (32.5 vs 11.1%), which bothered two thirds of the uncontrolled
and one third of partly controlled subjects. Asthma medications were used by
87.5% of the asthmatics, although around 30% of them who had insufficiently
controlled disease used only short-acting beta-agonists. Asthmatics also had
lower lung function, reacted to lower doses of methacholine that the controls and
13.6% of them had a FEV1/FVC ratio below 0.7. Allergic rhinitis was reported by
73.8% of the asthmatics and they were more frequently sensitized to several
common allergens. CONCLUSIONS: Approximately 60% of asthmatics from this
population-based study had insufficiently controlled asthma and persistent
complaints, despite a high use of asthma medications. These self-reported
symptoms were supported by clinical examination data. Increased cough frequency
is an indicator of a more severe and difficult to control disease and should be
considered when asthma is characterized.
PMID- 25135647
TI - Lipopolysaccharide induced LOX-1 expression via TLR4/MyD88/ROS activated p38MAPK
NF-kappaB pathway.
AB - Lectin-like receptor for oxidized low density lipoprotein (LOX-1) plays a key
role in endothelial ox-LDL endocytosis, endothelial dysfunction and
atherogenesis. In the present study, the effect of lipopolysaccharide (LPS) on
LOX-1 expression and the underlying molecular pathways were investigated. Human
umbilical vein endothelial cells (HUVECs) were treated with LPS and the protein
expressions of LOX-1, TLR4, TLR2, MyD88, Nox4, Nox2, PI3K, p38MAPK, JNK, ERK,
Nrf1, Nrf2 and p65 were examined by Western blotting. The intracellular reactive
oxygen species (ROS) production was examined by flow cytometry with fluorescence
probe DCFH2-DA. The role of TLR4, MyD88 and Nox4 were determined with specific
siRNA. The endothelial ox-LDL uptake and the endothelial-monocyte adhesion were
evaluated with DiI-ox-LDL and Hoechst 33342 respectively. The effect of LPS on
LOX-1 expression in aorta tissue was also studied with male C57/BL6 mice by
intraperitoneal injection of LPS. The results showed that LPS induced LOX-1
protein expression in a time- and concentration-dependent manner. The mRNA
expression of LOX-1 was also upregulated. The protein expression of LOX-1 and
phosphorylated p38MAPK, p65 was significantly enhanced by LPS both in vitro and
in vivo. LPS induced LOX-1 expression was blocked by siRNA for TLR4, MyD88, and
Nox4 and inhibitors for p38MAPK, NF-kappaB, cyclooxygenase-2, and NADPH oxidase.
Both LPS induced ox-LDL uptake and endothelial-monocyte adhesion were
significantly inhibited by anti-LOX-1 antibody. LPS dramatically induced LOX-1
protein expression in aorta tissues. In conclusion, our data suggested that LPS
induces LOX-1 expression via TLR4/MyD88/ROS activated p38MAPK/NF-kappaB pathway
in endothelial cells, which provides new regulatory mechanisms for LOX-1
expression.
PMID- 25135648
TI - Activation of Nrf2 by dimethyl fumarate improves vascular calcification.
AB - Dimethyl fumarate (DMF) has several pharmacological benefits including
immunomodulation and prevention of fibrosis, which are dependent on the NF-E2
related factor 2 (Nrf2) antioxidant pathways. Therefore, we hypothesized that DMF
could attenuate vascular calcification via Nrf2 activation. Vascular
calcification induced by hyperphosphataemia was significantly inhibited by DMF in
vascular smooth muscle cells (VSMCs) in a dose-dependent manner. DMF-mediated
Nrf2 upregulation was accompanied by the reduced expressions of genes related
with osteoblast-like phenotype based on promoter activity, mRNA and protein
expression, and von Kossa staining. Likewise, Nrf2 overexpression significantly
decreased the formation of calcium deposit similar to the level of osteogenic
staining in VSMCs, and DMF with Nrf2 knockdown failed to attenuate
hyperphosphatemia induced vascular calcification. Furthermore, DMF significantly
attenuated the calcification of ex vivo ring culture from both rat common carotid
artery and mouse thoracic aorta as well as in vivo mouse model of Vitamin D3
induced calcification consistent with the increased Nrf2 protein levels in early
stage of calcification by DMF. In conclusion, our data support that DMF
stimulates Nrf2 activity to attenuate hyperphosphatamia in vitro or Vitamin D3
induced in vivo vascular calcification, which would be a beneficial effect on
vascular diseases induced by oxidative stress such as vascular calcification.
PMID- 25135649
TI - Treatment of preeclampsia: current approach and future perspectives.
AB - Hypertension is the most common medical disorder encountered during pregnancy,
occurring in about 6-8 % of pregnancies. Preeclampsia is a pregnancy-specific
disorder that occurs after 20 weeks' gestation, characterized by hypertension and
proteinuria. Preeclampsia can also occur superimposed upon chronic hypertension.
Eclampsia is the convulsive form of preeclampsia, and affects 0.1 % of all
pregnancies. In low-income and middle-income countries, preeclampsia and
eclampsia are associated with 10-15 % of direct maternal deaths. Women who
develop preeclampsia in pregnancy are at greater risk of cardiovascular and
cerebrovascular events even years after their pregnancies. There is significant
progress in the elucidation of the underlying mechanisms and pathophysiology of
preeclampsia, although its therapeutics remains challenging; delivery of the
fetus is still the definitive treatment. Different international societies have
produced recommendations and guidelines for clinicians treating preeclampsia,
with an overall goal of improving maternal and fetal outcomes. In this review, we
focus on the level of blood pressure at which to commence treatment and the
current clinical management strategies available to treat and possibly prevent
preeclampsia. We also briefly outline some newer perspectives on management of
the disorder.
PMID- 25135650
TI - Severe and refractory solar urticaria treated with intravenous immunoglobulins: a
phase II multicenter study.
AB - BACKGROUND: Retrospective data have suggested the effectiveness of intravenous
immunoglobulins (IVIG) for solar urticaria (SU). OBJECTIVE: We sought to
prospectively assess the efficacy of IVIG for SU. METHODS: We conducted a
multicentric phase II study to test the efficacy of a single course of IVIG (2
g/kg) in patients with severe and refractory SU. The primary outcome was
remission of SU on phototesting at 12 weeks after IVIG treatment. Secondary
objectives included clinical remission, improved quality of life, and 50%
improvement in disease intensity as measured on a visual analog scale. RESULTS:
Of the 9 patients who received IVIG injection, 2 showed remission of SU on
phototesting, corresponding to a response rate of 22.2% (95% confidence interval
2.8%-60.0%). In all, 6 patients (67%) showed at least 1 response criterion after
4 weeks and 5 (56%) after 12 weeks. Response was maintained after 24 weeks for 2
patients and after 48 weeks for 1 patient. About half of the patients (56%) had
moderate to severe headache. LIMITATIONS: Lack of control arm and small number of
patients are limitations. CONCLUSION: A single course of IVIG appears
insufficient to obtain prolonged significant control of SU; future evaluation of
different schedules of IVIG administration is warranted.
PMID- 25135651
TI - Sustained activation of c-Jun N-terminal and extracellular signal-regulated
kinases in port-wine stain blood vessels.
AB - BACKGROUND: Port-wine stain (PWS) is a congenital, progressive vascular
malformation but the pathogenesis remains incompletely understood. OBJECTIVE: We
sought to investigate the activation status of various kinases, including
extracellular signal-regulated kinase, c-Jun N-terminal kinase, AKT,
phosphatidylinositol 3-kinase, P70 ribosomal S6 kinase, and phosphoinositide
phospholipase C gamma subunit, in PWS biopsy tissues. METHODS:
Immunohistochemistry was performed on 19 skin biopsy samples from 11 patients
with PWS. RESULTS: c-Jun N-terminal kinase, extracellular signal-regulated
kinase, and P70 ribosomal S6 kinase in pediatric and adult PWS blood vessels were
consecutively activated. Activation of AKT and phosphatidylinositol 3-kinase was
found in many adult hypertrophic PWS blood vessels but not in infants.
Phosphoinositide phospholipase C gamma subunit showed strong activation in
nodular PWS blood vessels. LIMITATION: Infantile PWS sample size was small.
CONCLUSION: Our data suggest a subsequent activation profile of various kinases
during different stages of PWS: (1) c-Jun N-terminal and extracellular signal
regulated kinases are firstly and consecutively activated in all PWS tissues,
which may contribute to both the pathogenesis and progressive development of PWS;
(2) AKT and phosphatidylinositol 3-kinase are subsequently activated, and are
involved in the hypertrophic development of PWS blood vessels; and (3)
phosphoinositide phospholipase C gamma subunit is activated in the most advanced
stage of PWS and may participate in nodular formation.
PMID- 25135653
TI - What efficacy measures are clinically relevant and should be used in Cochrane
Reviews of acute migraine trials? A viewpoint.
AB - BACKGROUND: Cochrane Reviews are methodologically of high quality but the
clinical relevance of analysed efficacy measures (EMs) should also be assessed.
METHODS: The clinical relevance of EMs used in one systematic Cochrane review of
oral zolmitriptan for migraine headache was evaluated. RESULTS: The following EMs
were used: pain free at two hours (30%), headache relief at two hours (60%),
sustained pain free for 24 hours (19%) and sustained headache relief for 24 hours
(39%). These EMs were also used in four other Cochrane reviews of acute migraine
treatment. Of these EMs sustained headache relief for 24 h is not judged
clinically relevant. CONCLUSION: Pain free and sustained pain free are clinically
relevant, but the responses are rather low, demonstrating that there is a need
for improvement of acute drug treatment in migraine.
PMID- 25135654
TI - Herpes zoster ophthalmicus following onabotulinumtoxinA administration for
chronic migraine: a case report and literature review.
AB - BACKGROUND: There is a growing body of literature documenting local herpes zoster
outbreak following procedures. The mechanism underlying these outbreaks remains
elusive. We present a case of zoster following onabotulinumtoxinA (BTX) for
migraine and a literature review. METHODS: Chart and literature review. CASE: A
72-year-old woman with chronic migraine received BTX injections for 3 years
without incident. She had a history of thoracic zoster with subsequent post
herpetic neuralgia. In August 2013, 48 hours after receiving BTX injections, she
developed a painful rash in the right V1 distribution consistent with herpes
zoster ophthalmicus. One week later the rash had resolved without treatment.
LITERATURE REVIEW: We identified 65 (including 2 from Juel-Jenson) cases of
zoster reactivation following minor procedures. These cases tend to be in young
patients without specific risk factors. Outbreaks characteristically occur at the
level of exposure to local trauma. DISCUSSION: Our review suggests that local
trauma, regardless of the nature of stimuli, may be sufficient for zoster
reactivation. We hypothesize that the stressors in these reported cases exert a
local epigenetic influence on viral transcription, allowing for viral
reactivation. CONCLUSION: Zoster is a potential complication of BTX
administration for chronic migraine in adults. Physician awareness can reduce the
significant morbidity associated with this disease.
PMID- 25135652
TI - A longitudinal study of urea cycle disorders.
AB - The Urea Cycle Disorders Consortium (UCDC) is a member of the NIH funded Rare
Diseases Clinical Research Network and is performing a longitudinal study of 8
urea cycle disorders (UCDs) with initial enrollment beginning in 2006. The
consortium consists of 14 sites in the U.S., Canada and Europe. This report
summarizes data mining studies of 614 patients with UCDs enrolled in the UCDC's
longitudinal study protocol. The most common disorder is ornithine
transcarbamylase deficiency, accounting for more than half of the participants.
We calculated the overall prevalence of urea cycle disorders to be 1/35,000, with
2/3rds presenting initial symptoms after the newborn period. We found the
mortality rate to be 24% in neonatal onset cases and 11% in late onset cases. The
most common precipitant of clinical hyperammonemic episodes in the post-neonatal
period was intercurrent infections. Elevations in both blood ammonia and
glutamine appeared to be biomarkers for neurocognitive outcome. In terms of
chronic treatment, low protein diet appeared to result in normal weight but
decreased linear growth while N-scavenger therapy with phenylbutyrate resulted in
low levels of branched chain amino acids. Finally, we found an unexpectedly high
risk for hepatic dysfunction in patients with ornithine transcarbamylase
deficiency. This natural history study illustrates how a collaborative study of a
rare genetic disorder can result in an improved understanding of morbidity and
disease outcome.
PMID- 25135656
TI - Hospital end-of-life treatment intensity among cancer and non-cancer cohorts.
AB - CONTEXT: Hospitals vary substantially in their end-of-life (EOL) treatment
intensity. It is unknown if patterns of EOL treatment intensity are consistent
across conditions. OBJECTIVES: To explore the relationship between hospitals'
cancer- and non-cancer-specific EOL treatment intensity. METHODS: We conducted a
retrospective cohort analysis of Pennsylvania acute care hospital admissions for
either cancer or congestive heart failure (CHF) and/or chronic obstructive
pulmonary disease (COPD) between 2001 and 2007, linked to vital statistics
through 2008. We calculated Bayes's shrunken case-mix standardized (observed-to
expected) ratios of intensive care and life-sustaining treatment use among two
EOL cohorts: those prospectively identified at high probability of dying on
admission and those retrospectively identified as terminal admissions
(decedents). We then summed these to create a hospital-specific prospective and
retrospective overall EOL treatment intensity index for cancer vs. CHF/COPD.
RESULTS: The sample included 207,523 admissions with 15% or greater predicted
probability of dying on admission among 172,041 unique adults and 120,372
terminal admissions at 166 hospitals; these two cohorts overlapped by 52,986
admissions. There was substantial variation between hospitals in their
standardized EOL treatment intensity ratios among cancer and CHF/COPD admissions.
Within hospitals, cancer- and CHF/COPD-specific standardized EOL treatment
intensity ratios were highly correlated for intensive care unit (ICU) admission
(prospective rho = 0.81; retrospective rho = 0.78), ICU lengths of stay (rho =
0.76; 0.64), mechanical ventilation (rho = 0.73; 0.73), and hemodialysis (rho =
0.60; 0.71) and less highly correlated for tracheostomy (rho = 0.43; 0.53) and
gastrostomy (rho = 0.29; 0.30). Hospitals' overall EOL intensity index for cancer
and CHF admissions were correlated (prospective rho = 0.75; retrospective rho =
0.75) and had equal group means (P-value = 0.631; 0.699). CONCLUSION: Despite
substantial difference between hospitals in EOL treatment intensity, within
hospital homogeneity in EOL treatment intensity for cancer- and non-cancer
populations suggests the existence of condition-insensitive institutional norms
of EOL treatment.
PMID- 25135655
TI - Differential expression of microRNAs in decidua-derived mesenchymal stem cells
from patients with pre-eclampsia.
AB - BACKGROUND: Mesenchymal stem cells (MSCs) at maternal-fetal interface are
considered to play an important role in the pathogenesis of pre-eclampsia (PE).
microRNAs (miRNAs) also have an important influence on differentiation,
maturation, and functions of MSCs. Our aim in this study was to determine the
differential expression of miRNAs in decidua-derived MSCs (dMSCs) from severe PE
and normal pregnancies. RESULTS: miRNA expression profiles in dMSCs from five
patients with severe PE and five healthy pregnant women were screened using
microarray. Then, bioinformatic analysis of the microarray results was performed.
Out of 179 differentially expressed miRNAs, 49 miRNAs had significant (p < 0.05)
differential expression of >= 2.0-fold changes, including 21 up-regulated and 28
down-regulated. miRNA-Gene-network and miRNA-Gene ontology (GO) -network analyses
were performed. Overall, 21 up-regulated and 15 down-regulated miRNAs showed high
degrees in these analyses. Moreover, the significantly enriched signaling
pathways and GOs were identified. The analyses revealed that pathways associated
with cell proliferation, angiogenesis, and immune functions were highly regulated
by the differentially expressed miRNAs, including Wnt signaling pathway, mitogen
activated protein kinase signaling pathway, transforming growth factor beta
signaling pathway, T-cell receptor signaling pathway, and B cell receptor
signaling pathway. Four miRNA predicted target genes, vascular endothelial growth
factor A (VEGFA), indoleamine 2,3-dioxygenase, suppression of cytokine signaling
3, and serine/threonine protein phosphatase 2A 55 kDa regulatory subunit B alpha
isoform (PPP2R2A) were all decreased in dMSCs from patients with PE. Furthermore,
the physiological roles of miR-16 and miR-136 in the down-regulation of VEGFA and
PPP2R2A, respectively, were confirmed through reporter assays. CONCLUSIONS: These
findings suggest that miRNAs in dMSCs may be important regulatory molecules in
the development of PE.
PMID- 25135657
TI - Capture, transfer, and feedback of patient-centered outcomes data in palliative
care populations: does it make a difference? A systematic review.
AB - CONTEXT: Patient-centered outcome measures (PCOMs) are an important way of
promoting patient-professional communication. However, evidence regarding their
implementation in palliative care is limited, as is evidence of the impact on
care quality and outcomes. OBJECTIVES: The aim was to systematically review
evidence on capture and feedback of PCOMs in palliative care populations and
determine the effects on processes and outcomes of care. METHODS: We searched
Medline, Embase, CINAHL, BNI, PsycINFO, and gray literature from 1985 to October
2013 for peer-reviewed articles focusing on collection, transfer, and feedback of
PCOMs in palliative care populations. Two researchers independently reviewed all
included articles. Review articles, feasibility studies, and those not measuring
PCOMs in clinical practice were excluded. We quality assessed articles using
modified Edwards criteria and undertook narrative synthesis. RESULTS: One hundred
eighty-four articles used 122 different PCOMs in 70,466 patients. Of these, 16
articles corresponding to 13 studies met the full inclusion criteria. Most
evidence was from outpatient oncology. There was strong evidence for an impact of
PCOMs feedback on processes of care including better symptom recognition, more
discussion of quality of life, and increased referrals based on PCOMs reporting.
There was evidence of improved emotional and psychological patient outcomes but
no effect on overall quality of life or symptom burden. CONCLUSION: In palliative
care populations, PCOMs feedback improves awareness of unmet need and allows
professionals to act to address patients' needs. It consequently benefits
patients' emotional and psychological quality of life. However, more high-quality
evidence is needed in noncancer populations and across a wider range of settings.
PMID- 25135658
TI - Fatigue is associated with serum interleukin-6 levels and symptoms of depression
in patients on chronic hemodialysis.
AB - CONTEXT: Little is known about activated immune-inflammatory pathways and
interleukin-6 (IL-6) in the development of fatigue and/or depression in patients
with end-stage renal disease on chronic hemodialysis (HD). OBJECTIVES: To
evaluate the possible correlation between fatigue and serum levels of IL-6 in
patients on chronic HD. METHODS: One hundred HD patients were assessed for the
presence of fatigue using the SF-36 Vitality subscale and were administered the
Beck Depression Inventory (BDI), the Hamilton Anxiety Rating Scale (HARS), the
Mini-Mental State Examination (MMSE), the activities of daily living (ADL), and
the instrumental activities of daily living (IADL). We also calculated the time
of recovery after hemodialysis (TIRD) and the number/severity of comorbidities
using the Charlson Comorbidity Index (CCI). Laboratory parameters were measured
as well as serum IL-6. RESULTS: Forty-three patients constituted the fatigued
group and 57 the nonfatigued group. Age, CCI, BDI, HARS, and TIRD were
significantly higher in fatigued patients than in the nonfatigued patients.
Conversely, the scores of ADL, IADL, and MMSE were significantly lower in
fatigued than in nonfatigued patients. Serum IL-6 levels (pg/mL) were higher in
the fatigued group (5.1 +/- 3.4) than in the nonfatigued group (1.6 +/- 1.5; P <
0.001); serum albumin and creatinine levels were significantly lower. Twenty-six
patients (26%) had no symptoms of depression (BDI score <10), and 74 patients
(74%) had symptoms of depression (BDI score >9). Patients with a BDI score >9
were older; had a higher CCI; a lower MMSE; a higher TIRD; lower serum albumin,
creatinine, and urea levels; and higher serum IL-6 levels. The correlation
analyses showed that the score of the SF-36 Vitality subscale was associated with
age, dialytic age, TIRD, ADL, IADL, CCI, BDI, HARS, MMSE, serum urea, creatinine,
albumin, and IL-6 levels. On multivariate general linear model analyses, with
fatigue as the dependent variable and gender as a second factor, BDI and serum IL
6 levels were independently associated with the score of the SF-36 Vitality
subscale. A canonical correlation analysis was performed including in the model
fatigue, BDI, and biomarkers; the correlation was 0.679 (R(2) = 0.462). Fatigue,
BDI, and IL-6 among biomarkers showed the strongest association with the
underlying construct (standardized canonical coefficients = -0.989, 0.015, and
0.852, respectively), thus explaining a correlation of IL-6 with both depression
and fatigue. CONCLUSION: Fatigue was significantly associated with symptoms of
depression and serum IL-6 levels in patients receiving chronic HD.
PMID- 25135660
TI - Effects of cargo molecules on membrane perturbation caused by transportan10 based
cell-penetrating peptides.
AB - Cell-penetrating peptides with the ability to escape endosomes and reach the
target are of great value as delivery vectors for different bioactive cargoes and
future treatment of human diseases. We have studied two such peptides, NickFect1
and NickFect51, both originated from stearylated transportan10 (PF3). To obtain
more insight into the mechanism(s) of peptide delivery and the biophysical
properties of an efficient vector system, we investigated the effect of different
bioactive oligonucleotide cargoes on peptide-membrane perturbation and peptide
structural induction. We studied the membrane interactions of the peptides with
large unilamellar vesicles and compared their effects with parent peptides
transportan10 and PF3. In addition, cellular uptake and peptide-mediated
oligonucleotide delivery were analyzed. Calcein leakage experiments showed that
similar to transportan10, NickFect51 caused a significant degree of membrane
leakage, whereas NickFect1, similar to PF3, was less membrane perturbing. The
results are in agreement with previously published results indicating that
NickFect51 is a more efficient endosomal escaper. However, the presence of a
large cargo like plasmid DNA inhibited NickFect's membrane perturbation and
cellular uptake efficiency of the peptide was reduced. We conclude that the
pathway for cellular uptake of peptide complexes is cargo dependent, whereas the
endosomal escape efficacy depends on peptide hydrophobicity and chemical
structure. For small interfering RNA delivery, NickFect51 appears to be optimal.
The biophysical signature shows that the peptide alone causes membrane
perturbation, but the cargo complex does not. These two biophysical
characteristics of the peptide and its cargo complex may be the signature of an
efficient delivery vector system.
PMID- 25135659
TI - Revisiting the bilayer structures of fluid phase phosphatidylglycerol lipids:
Accounting for exchangeable hydrogens.
AB - We recently published two papers detailing the structures of fluid phase
phosphatidylglycerol (PG) lipid bilayers (Kucerka et al., 2012 J. Phys. Chem. B
116: 232-239; Pan et al., 2012 Biochim. Biophys. Acta Biomembr. 1818: 2135-2148),
which were determined using the scattering density profile model. This hybrid
experimental/computational technique utilizes molecular dynamics simulations to
parse a lipid bilayer into components whose volume probabilities follow simple
analytical functional forms. Given the appropriate scattering densities, these
volume probabilities are then translated into neutron scattering length density
(NSLD) and electron density (ED) profiles, which are used to jointly refine
experimentally obtained small angle neutron and X-ray scattering data. However,
accurate NSLD and ED profiles can only be obtained if the bilayer's chemical
composition is known. Specifically, in the case of neutron scattering, the
lipid's exchangeable hydrogens with aqueous D2O must be accounted for, as they
can have a measureable effect on the resultant lipid bilayer structures. This was
not done in our above-mentioned papers. Here we report on the molecular
structures of PG lipid bilayers by appropriately taking into account the
exchangeable hydrogens. Analysis indicates that the temperature-averaged PG lipid
areas decrease by 1.5 to 3.8A(2), depending on the lipid's acyl chain length and
unsaturation, compared to PG areas when hydrogen exchange was not taken into
account.
PMID- 25135661
TI - Biochemical characterization and structure-function relationship of two plant
NCS2 proteins, the nucleobase transporters NAT3 and NAT12 from Arabidopsis
thaliana.
AB - Nucleobase ascorbate transporters (NATs), also known as Nucleobase:Cation
Symporter 2 (NCS2) proteins, belong to an evolutionary widespread family of
transport proteins with members in nearly all domains of life. We present the
biochemical characterization of two NAT proteins, NAT3 and NAT12 from Arabidopsis
thaliana after their heterologous expression in Escherichia coli UraA knockout
mutants. Both proteins were shown to transport adenine, guanine and uracil with
high affinities. The apparent KM values were determined with 10.12MUM, 4.85MUM
and 19.95MUM, respectively for NAT3 and 1.74MUM, 2.44MUM and 29.83MUM,
respectively for NAT12. Competition studies with the three substrates suggest
hypoxanthine as a further substrate of both transporters. Furthermore, the
transport of nucleobases was markedly inhibited by low concentrations of a proton
uncoupler indicating that NAT3 and NAT12 act as proton-nucleobase symporters.
Transient expression studies of NAT-GFP fusion constructs revealed a localization
of both proteins in the plasma membrane. Based on the structural information of
the uracil permease UraA from E. coli, a three-dimensional experimentally
validated homology model of NAT12 was created. The NAT12 structural model is
composed of 14 TM segments and divided into two inverted repeats of TM1-7 and TM8
14. Docking studies and mutational analyses identified residues involved in NAT12
nucleobase binding including Ser-247, Phe-248, Asp-461, Thr-507 and Thr-508. This
is the first study to provide insight into the structure-function of plant NAT
proteins, which reveals differences from the other members of the NCS2 protein
family.
PMID- 25135662
TI - Quantification of leakage from large unilamellar lipid vesicles by fluorescence
correlation spectroscopy.
AB - Fluorescence correlation spectroscopy (FCS) is a powerful experimental technique
that in recent years has found numerous applications for studying biological
phenomena. In this article, we scrutinize one of these applications, namely, FCS
as a technique for studying leakage of fluorescent molecules from large
unilamellar lipid vesicles. Specifically, we derive the mathematical framework
required for using FCS to quantify leakage of fluorescent molecules from large
unilamellar lipid vesicles, and we describe the appropriate methodology for
successful completion of FCS experiments. By use of this methodology, we show
that FCS can be used to accurately quantify leakage of fluorescent molecules from
large unilamellar lipid vesicles, including leakage of fluorescent molecules of
different sizes. To demonstrate the applicability of FCS, we have investigated
the antimicrobial peptide mastoparan X. We show that mastoparan X forms transient
transmembrane pores in POPC/POPG (3:1) vesicles, resulting in size-dependent
leakage of molecules from the vesicles. We conclude the paper by discussing some
of the advantages and limitations of FCS as compared to other existing methods to
measure leakage from large unilamellar lipid vesicles.
PMID- 25135663
TI - The periplasmic domain of Escherichia coli outer membrane protein A can undergo a
localized temperature dependent structural transition.
AB - Gram-negative bacteria such as Escherichia coli are surrounded by two membranes
with a thin peptidoglycan (PG)-layer located in between them in the periplasmic
space. The outer membrane protein A (OmpA) is a 325-residue protein and it is the
major protein component of the outer membrane of E. coli. Previous structure
determinations have focused on the N-terminal fragment (residues 1-171) of OmpA,
which forms an eight stranded transmembrane beta-barrel in the outer membrane.
Consequently it was suggested that OmpA is composed of two independently folded
domains in which the N-terminal beta-barrel traverses the outer membrane and the
C-terminal domain (residues 180-325) adopts a folded structure in the periplasmic
space. However, some reports have proposed that full-length OmpA can instead
refold in a temperature dependent manner into a single domain forming a larger
transmembrane pore. Here, we have determined the NMR solution structure of the C
terminal periplasmic domain of E. coli OmpA (OmpA(180-325)). Our structure
reveals that the C-terminal domain folds independently into a stable globular
structure that is homologous to the previously reported PG-associated domain of
Neisseria meningitides RmpM. Our results lend credence to the two domain
structure model and a PG-binding function for OmpA, and we could indeed localize
the PG-binding site on the protein through NMR chemical shift perturbation
experiments. On the other hand, we found no evidence for binding of OmpA(180-325)
with the TonB protein. In addition, we have also expressed and purified full
length OmpA (OmpA(1-325)) to study the structure of the full-length protein in
micelles and nanodiscs by NMR spectroscopy. In both membrane mimetic
environments, the recombinant OmpA maintains its two domain structure that is
connected through a flexible linker. A series of temperature-dependent HSQC
experiments and relaxation dispersion NMR experiments detected structural
destabilization in the bulge region of the periplasmic domain of OmpA above
physiological temperatures, which may induce dimerization and play a role in
triggering the previously reported larger pore formation.
PMID- 25135665
TI - Exciting: a full-potential all-electron package implementing density-functional
theory and many-body perturbation theory.
AB - Linearized augmented planewave methods are known as the most precise numerical
schemes for solving the Kohn-Sham equations of density-functional theory (DFT).
In this review, we describe how this method is realized in the all-electron full
potential computer package, exciting. We emphasize the variety of different
related basis sets, subsumed as (linearized) augmented planewave plus local
orbital methods, discussing their pros and cons and we show that extremely high
accuracy (microhartrees) can be achieved if the basis is chosen carefully. As the
name of the code suggests, exciting is not restricted to ground-state
calculations, but has a major focus on excited-state properties. It includes time
dependent DFT in the linear-response regime with various static and dynamical
exchange-correlation kernels. These are preferably used to compute optical and
electron-loss spectra for metals, molecules and semiconductors with weak electron
hole interactions. exciting makes use of many-body perturbation theory for
charged and neutral excitations. To obtain the quasi-particle band structure, the
GW approach is implemented in the single-shot approximation, known as G(0)W(0).
Optical absorption spectra for valence and core excitations are handled by the
solution of the Bethe-Salpeter equation, which allows for the description of
strongly bound excitons. Besides these aspects concerning methodology, we
demonstrate the broad range of possible applications by prototypical examples,
comprising elastic properties, phonons, thermal-expansion coefficients,
dielectric tensors and loss functions, magneto-optical Kerr effect, core-level
spectra and more.
PMID- 25135664
TI - Conformational heterogeneity of alpha-synuclein in membrane.
AB - alpha-Synuclein (alphaS) is a natively disordered protein in solution, thought to
be involved in the fusion of neurotransmitter vesicles to cellular membranes
during neurotransmission. Monomeric alphaS has been previously characterized in
two distinct membrane-associated conformations: a broken-helix structure, and an
extended helix. By employing atomistic molecular dynamics and a novel membrane
representation with significantly enhanced lipid mobility (HMMM), we investigate
the process of spontaneous membrane binding of alphaS and the conformational
dynamics of monomeric alphaS in its membrane-bound form. By repeatedly placing
helical alphaS monomers in solution above a planar lipid bilayer and observing
their spontaneous association and its spontaneous insertion into the membrane
during twenty independent unbiased simulations, we are able to characterize
alphaS in its membrane-bound state, suggesting that alphaS has a highly variable
membrane insertion depth at equilibrium. Our simulations also capture two
distinct states of alphaS, the starting broken-helix conformation seen in the
micelle bound NMR structures, and a semi-extended helix. Analysis of lipid
distributions near alphaS monomers indicates that the transition to a semi
extended helix is facilitated by concentration of phosphatidyl-serine headgroups
along the inner edge of the protein. Such a lipid-mediated transition between
helix-turn-helix and extended conformations of alphaS may also occur in vivo, and
may be important for the physiological function of alphaS.
PMID- 25135666
TI - The effect of changing micro-scale physical environmental factors on an
environment's invitingness for transportation cycling in adults: an exploratory
study using manipulated photographs.
AB - Previous studies have shown convincing evidence for positive relationships
between transportation cycling in adults and macro-scale physical environmental
factors. In contrast, relationships are less consistent for more changeable,
micro-scale environmental factors. The majority of existing studies used
observational study designs, which cannot determine causality. The present mixed
methods study used manipulated photographs to determine causal relationships
between micro-scale environmental factors and the environment's invitingness for
transportation cycling. Further, interactions among environmental factors and
moderating effects of gender, age and educational level were investigated. For
this study, panoramic photograph of a street was manipulated on eight
environmental factors: traffic, speed bump, general upkeep, evenness of the cycle
path, vegetation, separation of motorized traffic, separation with sidewalk and
cycle path width. Sixty-six middle-aged adults participated in the study and
sorted the manipulated panoramic photographs from least to most inviting to cycle
for transportation. Participants also provided qualitative data on how they
sorted the streets. Multilevel cross-classified modelling was used to analyse the
relationships between the environmental manipulations and the invitingness
scores. The qualitative data were deductively categorized according to the
environmental factors. All environmental factors, except for separation with
sidewalk, proved to have a significant main effect on the invitingness-score for
transportation cycling. Cycle path evenness appeared to have the strongest effect
on the invitingness. This effect was even stronger in an environment with good
compared to poorly overall upkeep. Another significant interaction effect showed
that the invitingness decreased when both separations along the cycle path were
present compared to only a separation with traffic. No moderating effects of the
demographic factors on these relationships were found. Qualitative data confirmed
the observed quantitative relationships and added depth and understanding.
Current study shows that the use of manipulated photographs can be an effective
way to examine environment-physical activity relationships. Our findings indicate
that evenness of the cycle path may be a crucial environmental factor when aiming
to increase a street's invitingness for transportation cycling among middle-aged
adults. The findings of our exploratory study could be used to develop an
environmental intervention to determine if our findings are applicable to real
changes in cycling behavior.
PMID- 25135668
TI - A self-report comorbidity questionnaire for haemodialysis patients.
AB - BACKGROUND: Patients with end-stage renal disease (ESRD) have multiple comorbid
conditions. Obtaining comorbidity data from medical records is cumbersome. A self
report comorbidity questionnaire is a useful alternative. Our aim in this study
was to examine the predictive value of a self-report comorbidity questionnaire in
terms of survival in ESRD patients. METHODS: We studied a prospective cross
sectional cohort of 282 haemodialysis (HD) patients in a single centre.
Participants were administered the self-report questionnaire during an HD
session. Information on their comorbidities was subsequently obtained from an
examination of the patient's medical records. Levels of agreement between
parameters derived from the questionnaire, and from the medical records, were
examined. Participants were followed-up for 18 months to collect survival data.
The influence on survival of comorbidity scores derived from the self-report data
(the Composite Self-report Comorbidity Score [CSCS]) and from medical records
data--the Charlson Comorbidity Index [CCI] were compared. RESULTS: The level of
agreement between the self-report items and those obtained from medical records
was almost perfect with respect the presence of diabetes (Kappa score kappa
0.97), substantial for heart disease and cancer (kappa 0.62 and kappa 0.72
respectively), moderate for liver disease (kappa 0.51), only fair for lung
disease, arthritis, cerebrovascular disease, and depression (kappa 0.34, 0.35,
0.34 and 0.29 respectively). The CSCS was strongly predictive of survival in
regression models (Nagelkerke R(2) value 0.202), with a predictive power similar
to that of the CCI (Nagelkerke R(2) value 0.211). The influences of these two
parameters were additive in the models--suggesting that these parameters make
different contributions to the assessment of comorbidity. CONCLUSION: This self
report comorbidity questionnaire is a viable tool to collect comorbidity data and
may have a role in the prediction of short-term survival in patients with end
stage renal disease on haemodialysis. Further work is required in this setting to
refine the tool and define its role.
PMID- 25135670
TI - Time-frequency analysis of the event-related potentials associated with the
Stroop test.
AB - Multiple executive processes are suggested to be engaged at Stroop test, and time
frequency analysis is acknowledged to improve the informative utility of EEG in
cognitive brain research. We aimed to investigate event-related oscillations
associated with the Stroop test. EEG data was collected from 23 healthy
volunteers while they performed a computer version of Stroop test. Both evoked
(phase-locked) and total (phase-locked+non-phase-locked) oscillatory responses in
the EEG were analyzed by wavelet transform. Data from the congruent (color-word
matching) and incongruent stimuli (color-word non-matching) conditions are
compared. In the incongruent condition, N450 wave was more negative and amplitude
of the late slow wave was more positive. In the time-frequency plane, the fronto
central total theta amplitude (300-700 ms) was larger in the incongruent
condition. The evoked delta (250-600 ms) was larger in the congruent condition
particularly over parieto-occipital regions. The larger frontal theta response in
the incongruent condition was associated with the detection of interference and
inhibition of the response to task-irrelevant features, while the larger evoked
delta in the congruent condition was suggestive of the easier decision process
owing to congruency between the physical attribute and the verbal meaning of the
stimuli. Furthermore, in the incongruent condition, amplitude of the occipital
total alpha in the very late phase (700-900 ms) was smaller. This prolonged
desynchronization in the alpha band could be reflecting augmentation of
attentional filters in visual modality for the next stimulus. These multiple
findings on EEG time-frequency plane provide improved description of the
overlapping processes in Stroop test.
PMID- 25135671
TI - Local country food sources of methylmercury, selenium and omega-3 fatty acids in
Nunavik, Northern Quebec.
AB - Country foods are central to Inuit culture and replete in selenium (Se) and long
chain omega-3 polyunsaturated fatty acids (n-3 PUFA). However, some marine
country foods bioaccumulate high concentrations of methylmercury (MeHg). Se and n
3 are associated with several health benefits in Nunavik, Northern Quebec, but,
recent studies show that prenatal MeHg exposure is associated with visual,
cognitive and behavioral deficit later in childhood. The study objectives are to
identify contemporary country food sources of MeHg, Se and long-chain n-3 PUFA in
Nunavik, particularly among childbearing-age women, taking into account regional
differences in consumption profiles. The contribution of different country foods
to daily MeHg, Se, long-chain n-3 PUFA intake (MUg/kg body weight/day) was
estimated using: (i) country food consumption and blood biomarkers data from the
2004 Nunavik Health Survey (387 women, 315 men), and (ii) data on MeHg, Se, long
chain n-3 PUFA concentrations found in Nunavik wildlife species. In the region
where most traditional beluga hunting takes place in Nunavik, the prevalence of
at-risk blood Hg (>= 8 MUg/L) in childbearing-age women was 78.4%. While most
country foods presently consumed contain low MeHg, beluga meat, not a staple of
the Inuit diet, is the most important contributor to MeHg: up to two-thirds of
MeHg intake in the beluga-hunting region (0.66 of MeHg intake) and to about one
third in other regions. In contrast, seal liver and beluga mattaaq - beluga skin
and blubber - only mildly contributed to MeHg (between 0.06 and 0.15 of MeHg
intake), depending on the region. Beluga mattaaq also highly contributed to Se
intake (0.30 of Se intake). Arctic char, beluga blubber and mattaaq, and seal
blubber contributed to most long-chain n-3 PUFA intake. This study highlights the
importance of considering interconnections between local ecosystems and dietary
habits to develop recommendations and interventions promoting country foods'
benefits, while minimizing the risk of MeHg from beluga meat, especially for
childbearing-age women.
PMID- 25135672
TI - The genome of a clinical Klebsiella variicola strain reveals virulence-associated
traits and a pl9-like plasmid.
AB - Klebsiella species frequently cause clinically relevant human infections
worldwide. We report the draft genome sequence of a Brazilian clinical isolate
(Bz19) of the recently recognized species Klebsiella variicola. The comparison of
Bz19 genome content with the At-22 (environmental K. variicola) and several
clinical Klebsiella pneumoniae shows that these species share a set of virulence
associated determinants. Of note, this K. variicola strain harbours a plasmid
like element that shares the same backbone present in a multidrug-resistant
plasmid found in a clinical K. pneumoniae isolated in USA.
PMID- 25135673
TI - Protein systems biology: method, regulation, and network.
PMID- 25135669
TI - The development and application of a quantitative peptide microarray based
approach to protein interaction domain specificity space.
AB - Protein interaction domain (PID) linear peptide motif interactions direct diverse
cellular processes in a specific and coordinated fashion. PID specificity, or the
interaction selectivity derived from affinity preferences between possible PID
peptide pairs is the basis of this ability. Here, we develop an integrated
experimental and computational cellulose peptide conjugate microarray (CPCMA)
based approach for the high throughput analysis of PID specificity that provides
unprecedented quantitative resolution and reproducibility. As a test system, we
quantify the specificity preferences of four Src Homology 2 domains and 124
physiological phosphopeptides to produce a novel quantitative interactome. The
quantitative data set covers a broad affinity range, is highly precise, and
agrees well with orthogonal biophysical validation, in vivo interactions, and
peptide library trained algorithm predictions. In contrast to preceding
approaches, the CPCMAs proved capable of confidently assigning interactions into
affinity categories, resolving the subtle affinity contributions of residue
correlations, and yielded predictive peptide motif affinity matrices. Unique
CPCMA enabled modes of systems level analysis reveal a physiological interactome
with expected node degree value decreasing as a function of affinity, resulting
in minimal high affinity binding overlap between domains; uncover that Src
Homology 2 domains bind ligands with a similar average affinity yet strikingly
different levels of promiscuity and binding dynamic range; and parse with
unprecedented quantitative resolution contextual factors directing specificity.
The CPCMA platform promises broad application within the fields of PID
specificity, synthetic biology, specificity focused drug design, and network
biology.
PMID- 25135674
TI - Identification of important positions within miRNAs by integrating sequential and
structural features.
AB - MicroRNA(miRNA) is a small, single stranded non-coding RNA which plays an
important regulatory role in gene expression. Additionally, miRNAs perform
crucial functions in a wide range of biological processes. These functions may be
exploited for miRNA-mediated regulation of protein-protein interaction and thus
protein function. Many computational methods have been developed to predict the
miRNA targets and to explore the regulatory mechanism between miRNA and protein.
However, the efforts to investigate important positions within miRNAs are not
comprehensive. This paper presents a framework to identify important positions
using collision entropy. The information of contained in the sequence and
secondary structure of miRNAs is considered. Further, the single base collision
entropy and the adjacent base related collision entropy are integrated to measure
the importance of miRNA position. Two thresholds are employed to select those
positions with more biological meaning. A dataset of Drosophila melanogaster is
used in the experiments. The results demonstrate that our approach can find
interesting and important positions within miRNAs and may lead to a better
understanding of miRNA biogenesis and function.
PMID- 25135675
TI - The effect of the different methods indicating 100/min to 120/min using the
metronome in dispatcher-assisted resuscitation.
PMID- 25135677
TI - The importance of lead aVR interpretation by emergency physicians.
PMID- 25135676
TI - The impact of age and gender on resource utilization and profitability in ED
patients seen and released.
AB - OBJECTIVE: To determine how age and gender impact resource utilization and
profitability in patients seen and released from an Emergency Department (ED).
METHODS: Billing data for patients seen and released from an Emergency Department
(ED) with >100,000 annual visits between 2003 and 2009 were collected. Resource
utilization was measured by length of stay (placement in ED bed to leaving the
bed) and direct clinical costs (e.g., ED nursing salary and benefits, pharmacy
and supply costs, etc.) estimated using relative value unit cost accounting. The
primary outcome of profitability was defined as contribution margin per hour. A
patient's contribution margin by insurance type (excluding self-pay) was
determined by subtracting direct clinical costs from facility contractual
revenue. Results are expressed as medians and US dollars. RESULTS: In 523 882
outpatient ED encounters, as patients' aged, length of stay and direct clinical
cost increased while the contribution margin and contribution margin by hour
decreased. Women of childbearing age (15-44) had higher median length of stay
(2.1 hours), direct clinical cost ($149), and contribution margin per hour
($103/hour) than men of same age (1.7, $131, $85/hour, respectively). Resource
utilization and profitability by gender were similar in children and adults over
45. CONCLUSION: Resource utilization increased and profitability decreased with
increasing age in patients seen and released from an ED. The care of women of
childbearing age resulted in higher resource utilization and higher profitability
than men of the same age. No differences in resource utilization or profitability
by gender were observed in children and adults over 45.
PMID- 25135678
TI - Reinforcement of anchorage during orthodontic brace treatment with implants or
other surgical methods.
AB - BACKGROUND: The term anchorage in orthodontic treatment refers to methods of
controlling unwanted tooth movement. This is provided either by anchor sites
within the mouth, such as the teeth and the palate, or from outside the mouth
(headgear). Recently, new methods of providing anchorage have been developed
using orthodontic implants which are surgically inserted into the bone in the
mouth. This is termed surgical anchorage. This is an update of a Cochrane review
first published in 2007. OBJECTIVES: To assess the effects of surgical anchorage
techniques compared to conventional anchorage in the prevention of unwanted tooth
movement in patients undergoing orthodontic treatment by evaluating the
mesiodistal movement of upper first molar teeth. A secondary objective was to
compare the effects of one type of surgical anchorage with another. SEARCH
METHODS: We searched the Cochrane Oral Health Group's Trials Register (to 28
October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The
Cochrane Library 2013, Issue 9), MEDLINE via OVID (1946 to 28 October 2013) and
EMBASE via OVID (1980 to 28 October 2013). We handsearched key international
orthodontic and dental journals, and searched the trial database
ClinicalTrials.gov and the World Health Organization (WHO) International Clinical
Trials Registry Platform for ongoing and unpublished studies. SELECTION CRITERIA:
Randomised controlled trials comparing surgical anchorage with conventional
anchorage in orthodontic patients. Trials comparing two types of surgical
anchorage were also included. DATA COLLECTION AND ANALYSIS: At least two review
authors independently and in duplicate extracted data and carried out risk of
bias assessments. We contacted study authors to clarify aspects of study design
and conduct, and to obtain unreported data. MAIN RESULTS: Fourteen new studies
were added in this update resulting in a total of 15 studies reporting data from
561 randomised patients. The studies were conducted in Europe, India, China,
South Korea and the USA. The age range of patients was commonly restricted to
adolescents or young adults, however the participants of two studies were from a
much wider age range (12 to 54 years). The distribution of males and females was
similar in eight of the studies, with a predominance of female patients in seven
studies.Eight studies were assessed to be at high overall risk of bias; six
studies at unclear risk of bias; one study at low risk of bias.Ten studies with
407 randomised and 390 analysed patients compared surgical anchorage with
conventional anchorage for the primary outcome of mesiodistal movement of upper
first molars. We carried out a random-effects model meta-analysis for the seven
studies that fully reported this outcome. There was strong evidence of an effect
of surgical anchorage on this outcome. Compared with conventional anchorage,
surgical anchorage was more effective in the reinforcement of anchorage by 1.68
mm (95% confidence interval (CI) -2.27 mm to -1.09 mm; seven studies, 308
participants analysed) with moderate quality of evidence (one study at high
overall risk of bias, five studies at unclear risk of bias, one study at low risk
of bias). This result should be interpreted with some caution, however, as there
was a substantial degree of heterogeneity for this comparison. There was no
evidence of a difference in overall duration of treatment between surgical and
conventional anchorage (-0.15 years; 95% CI -0.37 years to 0.07 years; three
studies, 111 analysed patients) with low quality of evidence (one study at high
overall risk of bias and two studies at unclear risk of bias). Information on
patient-reported outcomes such as pain and acceptability was limited and
inconclusive.When direct comparisons were made between two types of surgical
anchorage, there was a lack of evidence to suggest that any one technique was
better than another.No included studies reported adverse effects. AUTHORS'
CONCLUSIONS: There is moderate quality evidence that reinforcement of anchorage
is more effective with surgical anchorage than conventional anchorage, and that
results from mini-screw implants are particularly promising. While surgical
anchorage is not associated with the inherent risks and compliance issues related
to extraoral headgear, none of the included studies reported on harms of surgical
or conventional anchorage.
PMID- 25135679
TI - Celebrating our success--one state at a time.
PMID- 25135680
TI - Prevalence and outcomes of renal transplantation in children with intellectual
disability.
AB - To describe the prevalence and outcomes of renal transplantation in children with
ID we performed a retrospective cohort analysis of all children receiving a first
kidney-alone transplant in the UNOS dataset from 2008 to 2011. Recipients with
definite, probable, and without ID were compared using chi-square tests. Kaplan
Meier curves were constructed for patient and graft survival. Cox proportional
hazard models were used to estimate the association between ID and graft failure
and patient survival. Over the study period, 332 children with definite (117) or
probable (215) ID underwent first renal transplant, accounting for 16% of all
first pediatric renal transplants (n = 2076). Children with definite ID were not
significantly different from children without ID with respect to sex, ethnicity,
or prevalence of acute rejection. ID was associated with increased likelihood of
deceased donor source. ID was not significantly associated with decreased graft
or patient survival. In this first large-scale study, up to 16% of first
pediatric renal transplants were performed in children with ID. Short-term graft
and patient survival after transplant were equivalent between children with and
without ID. Further research is needed to examine long-term outcomes of
transplant in this population.
PMID- 25135681
TI - Characterization of wheat germ agglutinin lectin-reactive glycosylated OmpA-like
proteins derived from Porphyromonas gingivalis.
AB - Glycosylation is one of the common posttranslational modifications in eukaryotes.
Recently, glycosylated proteins have also been identified in prokaryotes. A few
glycosylated proteins, including gingipains, have been identified in
Porphyromonas gingivalis, a major pathogen associated with chronic periodontitis.
However, no other glycosylated proteins have been found. The present study
identified glycoproteins in P. gingivalis cell lysates by lectin blotting. Whole
cell lysates reacted with concanavalin A (ConA), Lens culinaris agglutinin (LCA),
Phaseolus vulgaris erythroagglutinin (PHA-E4), and wheat germ agglutinin (WGA),
suggesting the presence of mannose-, N-acetylgalactosamine-, or N
acetylglucosamine (GlcNAc)-modified proteins. Next, glycoproteins were isolated
by ConA-, LCA-, PHA-E4-, or WGA-conjugated lectin affinity chromatography
although specific proteins were enriched only by the WGA column. Mass
spectrometry analysis showed that an OmpA-like, heterotrimeric complex formed by
Pgm6 and Pgm7 (Pgm6/7) was the major glycoprotein isolated from P. gingivalis.
Deglycosylation experiments and Western blotting with a specific antibody
indicated that Pgm6/7 was modified with O-GlcNAc. When whole-cell lysates from P.
gingivalis mutant strains with deletions of Pgm6 and Pgm7 were applied to a WGA
column, homotrimeric Pgm7, but not Pgm6, was isolated. Heterotrimeric Pgm6/7 had
the strongest affinity for fibronectin of all the extracellular proteins tested,
whereas homotrimeric Pgm7 showed reduced binding activity. These findings suggest
that the heterotrimeric structure is important for the biological activity of
glycosylated WGA-binding OmpA-like proteins in P. gingivalis.
PMID- 25135682
TI - Association and virulence gene expression vary among serotype III group B
streptococcus isolates following exposure to decidual and lung epithelial cells.
AB - Group B Streptococcus (GBS) causes severe disease in neonates, the elderly, and
immunocompromised individuals. GBS species are highly diverse and can be
classified by serotype and multilocus sequence typing. Sequence type 17 (ST-17)
strains cause invasive neonatal disease more frequently than strains of other
STs. Attachment and invasion of host cells are key steps in GBS pathogenesis. We
investigated whether four serotype III strains representing ST-17 (two strains),
ST-19, and ST-23 differ in their abilities to attach to and invade both decidual
cells and lung epithelial cells. Virulence gene expression following host cell
association and exposure to amnion cells was also tested. The ST-17 strains
differed in their abilities to attach to and invade decidual cells, whereas there
were no differences with lung epithelial cells. The ST-19 and ST-23 strains,
however, attached to and invaded decidual cells less than both ST-17 strains.
Although the ST-23 strain attached to lung epithelial cells better than ST-17 and
-19 strains, none of the strains effectively invaded the lung epithelial cells.
Notably, the association with host cells resulted in the differential expression
of several virulence genes relative to basal expression levels. Similar
expression patterns of some genes were observed regardless of cell type used.
Collectively, these results show that GBS strains differ in their abilities to
attach to distinct host cell types and express key virulence genes that are
relevant to the disease process. Enhancing our understanding of pathogenic
mechanisms could aid in the identification of novel therapeutic targets or
vaccine candidates that could potentially decrease morbidity and mortality
associated with neonatal infections.
PMID- 25135683
TI - Early innate immunity to bacterial infection in the lung is regulated
systemically by the commensal microbiota via nod-like receptor ligands.
AB - The commensal microbiota is a major regulator of the immune system. The majority
of commensal bacteria inhabit the gastrointestinal tract and are known to
regulate local mucosal defenses against intestinal pathogens. There is growing
appreciation that the commensal microbiota also regulates immune responses at
extraintestinal sites. Currently, however, it is unclear how this influences host
defenses against bacterial infection outside the intestine. Microbiota depletion
caused significant defects in the early innate response to lung infection by the
major human pathogen Klebsiella pneumoniae. After microbiota depletion, early
clearance of K. pneumoniae was impaired, and this could be rescued by
administration of bacterial Nod-like receptor (NLR) ligands (the NOD1 ligand
MurNAcTri(DAP) and NOD2 ligand muramyl dipeptide [MDP]) but not bacterial Toll
like receptor (TLR) ligands. Importantly, NLR ligands from the gastrointestinal,
but not upper respiratory, tract rescued host defenses in the lung. Defects in
early innate immunity were found to be due to reduced reactive oxygen species
mediated killing of bacteria by alveolar macrophages. These data show that
bacterial signals from the intestine have a profound influence on establishing
the levels of antibacterial defenses in distal tissues.
PMID- 25135684
TI - Homeostasis of N-alpha-terminal acetylation of EsxA correlates with virulence in
Mycobacterium marinum.
AB - The mycobacterial Esx-1 (ESAT-6 system 1) exporter translocates virulence factors
across the cytoplasmic membrane to the cell wall, cell surface, and the
bacteriological medium in vitro. The mechanisms underlying substrate targeting to
distinct locations are unknown. Several Esx-1 substrates are N-alpha-terminally
acetylated. The role of this rare modification in bacteria is unclear. We sought
to identify genes required for Esx-1 substrate modification, transport, and
localization. Pathogenic mycobacteria lyse Acanthamoeba castellanii in an Esx-1
dependent manner. We conducted a genetic screen to identify Mycobacterium marinum
strains which failed to lyse amoebae. We identified a noncytotoxic M. marinum
strain with a transposon insertion in a predicted N-alpha-terminal
acetyltransferase not previously linked to mycobacterial pathogenesis. Disruption
of this gene led to attenuation of virulence, failure to induce a type I
interferon response during macrophage infection, and loss of hemolytic activity.
The major Esx-1 substrates, EsxA and EsxB, were exported to the cell surface, but
only low levels were released into the bacteriological medium. The balance of
EsxA N-alpha-terminal acetylation was disrupted, resulting in a mycobacterial
strain in which surface-associated EsxA was hyperacetylated. Genetic
complementation completely restored Esx-1 function and the levels of N-alpha
terminally acetylated EsxA on the surface but restored only low levels of Esx-1
substrates in the bacteriological medium. Our results reveal a novel gene
required for mycobacterial Esx-1 export. Our findings indicate that maintaining
the homeostasis of Esx-1 substrate N-alpha-terminal acetylation is essential for
Esx-1-mediated virulence. We propose an inverse correlation between EsxA
acetylation and virulence.
PMID- 25135685
TI - Dynamic changes in the Streptococcus pneumoniae transcriptome during transition
from biofilm formation to invasive disease upon influenza A virus infection.
AB - Streptococcus pneumoniae is a leading cause of infectious disease globally.
Nasopharyngeal colonization occurs in biofilms and precedes infection. Prior
studies have indicated that biofilm-derived pneumococci are avirulent. However,
influenza A virus (IAV) infection releases virulent pneumococci from biofilms in
vitro and in vivo. Triggers of dispersal include IAV-induced changes in the
nasopharynx, such as increased temperature (fever) and extracellular ATP (tissue
damage). We used whole-transcriptome shotgun sequencing (RNA-seq) to compare the
S. pneumoniae transcriptome in biofilms, bacteria dispersed from biofilms after
exposure to IAV, febrile-range temperature, or ATP, and planktonic cells grown at
37 degrees C. Compared with biofilm bacteria, actively dispersed S. pneumoniae,
which were more virulent in invasive disease, upregulated genes involved in
carbohydrate metabolism. Enzymatic assays for ATP and lactate production
confirmed that dispersed pneumococci exhibited increased metabolism compared to
those in biofilms. Dispersed pneumococci also upregulated genes associated with
production of bacteriocins and downregulated colonization-associated genes
related to competence, fratricide, and the transparent colony phenotype. IAV had
the largest impact on the pneumococcal transcriptome. Similar transcriptional
differences were also observed when actively dispersed bacteria were compared
with avirulent planktonic bacteria. Our data demonstrate complex changes in the
pneumococcal transcriptome in response to IAV-induced changes in the environment.
Our data suggest that disease is caused by pneumococci that are primed to move to
tissue sites with altered nutrient availability and to protect themselves from
the nasopharyngeal microflora and host immune response. These data help explain
pneumococcal virulence after IAV infection and have important implications for
studies of S. pneumoniae pathogenesis.
PMID- 25135687
TI - Contributions of NanI sialidase to Caco-2 cell adherence by Clostridium
perfringens type A and C strains causing human intestinal disease.
AB - Previous studies showed that Clostridium perfringens type D animal disease strain
CN3718 uses NanI sialidase for adhering to enterocyte-like Caco-2 cells. The
current study analyzed whether NanI is similarly important when type A and C
human intestinal disease strains attach to Caco-2 cells. A PCR survey determined
that the nanI gene was absent from typical type A food poisoning (FP) strains
carrying a chromosomal enterotoxin (CPE) gene or the genetically related type C
Darmbrand (Db) strains. However, the nanI gene was present in type A strains from
healthy humans, type A strains causing CPE-associated antibiotic-associated
diarrhea (AAD) or sporadic diarrhea (SD), and type C Pig-Bel strains. Consistent
with NanI sialidase being the major C. perfringens sialidase when produced, FP
and Db strains had little supernatant sialidase activity compared to other type A
or C human intestinal strains. All type A and C human intestinal strains bound to
Caco-2 cells, but NanI-producing strains had higher attachment levels. When
produced, NanI can contribute to host cell attachment of human intestinal disease
strains, since a nanI null mutant constructed in type A SD strain F4969 had lower
Caco-2 cell adhesion than wild-type F4969 or a complemented strain. Further
supporting a role for NanI in host cell attachment, sialidase inhibitors reduced
F4969 adhesion to Caco-2 cells. Collectively, these results suggest that NanI may
contribute to the intestinal attachment and colonization needed for the chronic
diarrhea of CPE-associated AAD and SD, but this sialidase appears to be
dispensable for the acute pathogenesis of type A FP or type C enteritis
necroticans.
PMID- 25135686
TI - Lipopolysaccharides belonging to different Salmonella serovars are differentially
capable of activating Toll-like receptor 4.
AB - Salmonella enterica subsp. enterica serovar (serotype) Abortusovis is a member of
the Enterobacteriaceae. This serotype is naturally restricted to ovine species
and does not infect humans. Limited information is available about the immune
response of sheep to S. Abortusovis. S. Abortusovis, like Salmonella enterica
subsp. enterica serovar Typhi, causes a systemic infection in which, under
natural conditions, animals are not able to raise a rapid immune response.
Failure to induce the appropriate response allows pathogens to reach the placenta
and results in an abortion. Lipopolysaccharides (LPSs) are pathogen-associated
molecular patterns (PAMPs) that are specific to bacteria and are not synthesized
by the host. Toll-like receptors (TLRs) are a family of receptors that
specifically recognize PAMPs. As a first step, we were able to identify the
presence of Toll-like receptor 4 (TLR4) on the ovine placenta by using an
immunohistochemistry technique. To our knowledge, this is the first work
describing the interaction between S. Abortusovis LPS and TLR4. Experiments using
an embryonic cell line (HEK293) transfected with human and ovine TLR4s showed a
reduction of interleukin 8 (IL-8) production by S. Abortusovis and Salmonella
enterica subsp. enterica serovar Paratyphi upon LPS stimulation compared to
Salmonella enterica subsp. enterica serovar Typhimurium. Identical results were
observed using heat-killed bacteria instead of LPS. Based on data obtained with
TLR4 in vitro stimulation, we demonstrated that the serotype S. Abortusovis is
able to successfully evade the immune system whereas S. Typhimurium and other
serovars fail to do so.
PMID- 25135689
TI - Closure of a large, persistent enterocutaneous fistula by use of a ventricular
septal occluder.
PMID- 25135688
TI - Numeracy and literacy independently predict patients' ability to identify out-of
range test results.
AB - BACKGROUND: Increasing numbers of patients have direct access to laboratory test
results outside of clinical consultations. This offers increased opportunities
for both self-management of chronic conditions and advance preparation for clinic
visits if patients are able to identify test results that are outside the
reference ranges. OBJECTIVE: Our objective was to assess whether adults can
identify laboratory blood test values outside reference ranges when presented in
a format similar to some current patient portals implemented within electronic
health record (EHR) systems. METHODS: In an Internet-administered survey, adults
aged 40-70 years, approximately half with diabetes, were asked to imagine that
they had type 2 diabetes. They were shown laboratory test results displayed in a
standard tabular format. We randomized hemoglobin A1c values to be slightly
(7.1%) or moderately (8.4%) outside the reference range and randomized other test
results to be within or outside their reference ranges (ie, multiple deviations).
We assessed (1) whether respondents identified the hemoglobin A1c level as
outside the reference range, (2) how respondents rated glycemic control, and (3)
whether they would call their doctor. We also measured numeracy and health
literacy. RESULTS: Among the 1817 adult participants, viewing test results with
multiple deviations increased the probability of identifying hemoglobin A1c
values as outside the reference range (participants with diabetes: OR 1.47, 95%
CI 1.12-1.92, P=.005; participants without diabetes: OR 1.50, 95% CI 1.13-2.00,
P=.005). Both numeracy and health literacy were significant predictors of
correctly identifying out-of-range values. For participants with diabetes,
numeracy OR 1.32 per unit on a 1-6 scale (95% CI 1.15-1.51, P<.001) and literacy
OR 1.59 per unit of a 1-5 scale (95% CI 1.35-1.87, P<.001); for participants
without diabetes, numeracy OR 1.36 per unit (95% CI 1.17-1.58, P<.001) and
literacy OR 1.33 per unit (95% CI 1.12-1.58, P=.001). Predicted probabilities
suggested 77% of higher numeracy and health literacy participants, but only 38%
of lower numeracy and literacy participants, could correctly identify the
hemoglobin A1c levels as outside the reference range. Correct identification
reduced perceived blood glucose control (mean difference 1.68-1.71 points on a 0
10 scale, P<.001). For participants with diabetes, increased health literacy
reduced the likelihood of calling one's doctor when hemoglobin A1c=7.1% (OR 0.66
per unit, 95% CI 0.52-0.82, P<.001) and increased numeracy increased intention to
call when hemoglobin A1c=8.4% (OR 1.36 per unit, 95% CI 1.10-1.69, P=.005).
CONCLUSIONS: Limited health literacy and numeracy skills are significant barriers
to basic use of laboratory test result data as currently presented in some EHR
portals. Regarding contacting their doctor, less numerate and literate
participants with diabetes appear insensitive to the hemoglobin A1c level shown,
whereas highly numerate and literate participants with diabetes appear very
sensitive. Alternate approaches appear necessary to make test results more
meaningful.
PMID- 25135690
TI - Arginine Supplementation Induces Arginase Activity and Inhibits TNF-alpha
Synthesis in Mice Spleen Macrophages After Intestinal Obstruction.
AB - BACKGROUND: The purpose of this study was to assess the effect of arginine
supplementation on arginase activity, tumor necrosis factor-alpha (TNF-alpha) and
interleukin-10 (IL-10) synthesis in cultured splenic macrophages from a murine
model of intestinal obstruction (IO). The effects of nitric oxide synthase (iNOS)
inhibition were also studied using iNOS knockout animals. MATERIAL AND METHODS:
Male C57BL6/J wild-type (WT) and iNOS knockout (iNOS-/-) mice were randomized
into 6 groups: Sham and Sham-/- (standard chow), IO and IO-/- (standard chow +
IO), and Arg and Arg-/- (standard chow supplemented with arginine + IO). After 7
days of treatment with standard or supplemented chow, IO was induced. Arginase
activity as well as TNF-alpha and IL-10 levels were analyzed in splenic
macrophage cultures. RESULTS: Arginine supplementation and the absence of iNOS
increased arginase activity in splenic macrophages (Arg, IO-/-, and Arg-/- groups
vs the Sham group; P < .05). Arginine was also related to a decrease in TNF-alpha
levels (Arg vs IO group, P < .05) and maintenance of IL-10 levels (Arg vs other
groups, P > .05). The inhibition of iNOS did not result in effects on the
concentration of cytokines (Sham-/-, IO-/-, and Arg-/- vs other, P < .05).
CONCLUSIONS: Arginine supplementation and iNOS inhibition led to increased
arginase activity. Arginine availability decreased plasma TNF-alpha levels, which
may be directly related to nitric oxide derived from arginine.
PMID- 25135691
TI - Cephalotaxus griffithii Hook.f. needle extract induces cell cycle arrest,
apoptosis and suppression of hTERT and hTR expression on human breast cancer
cells.
AB - BACKGROUND: Cephalotaxus spp. are known to possess anticancer potential. In this
present work, for the first time the effects of C. griffithii needle (CGN)
extracts on human cancer cells were examined. METHODS: The CGN was successively
extracted with petroleum ether (PE), acetone and methanol. The extracts were
tested for its effect on proliferation of cancer cells (MTT assay on HeLa, ZR751
and HepG2). Extract that showed the maximum growth inhibitory effect was
subjected for mechanism of action study. These included apoptosis (morphological
and DNA fragmentation assay), cell cycle (flow cytometry), caspase expression
(Western blot) and activity (assay kit), p53 (western blot and TP53 siRNA
interference) and telomerase expression (reverse transcriptase PCR) analysis.
RESULTS: Among the extracts, PE extract induced maximum cytotoxicity, with
highest death occurred in ZR751 cells. Since, PE extract induced cell death was
highest among the CGN extracts, with maximum cancer cell death occurred in ZR751
cells; we carried out mechanism study of PE extract induced ZR751 cell death. It
was observed that PE extract induced ZR751 cell death was associated with cell
cycle arrest and apoptosis by activating both intrinsic and extrinsic apoptotic
pathways. Knock down study revealed that p53 is essential for loss of ZR751 cell
viability induced by PE extract. Further, PE extract down-regulated hTERT, hTR,
and c-Myc expression. Thin layer chromatography analysis indicated the presence
of unique phytochemicals in PE extract. CONCLUSION: Based on the observations, we
concluded that PE extract of C. griffithii needle contains important phyto
components with multiple cellular targets for control of breast cancer and is
worthy of future studies.
PMID- 25135692
TI - CD34(+)CD38(-)CD58(-) cells are leukemia-propagating cells in Philadelphia
chromosome-positive acute lymphoblastic leukemia.
PMID- 25135693
TI - Mycetoma caused by Nocardia brasiliensis in an immunocompetent patient.
PMID- 25135695
TI - Letter from the editor.
PMID- 25135694
TI - Ultrasound prediction of perinatal outcome: the unrecognised value of sibling
data.
AB - OBJECTIVE: To identify high-risk fetuses at the first routinely performed
ultrasound examination by making use of information from the mother's previous
pregnancy. DESIGN: A population-based cohort study. SETTING: Norway, 1999-2009.
POPULATION: All singleton first live births and their second-born siblings
registered in the Medical Birth Registry of Norway (166,786 eligible sibling
pairs). METHODS: Odds ratios were calculated by logistic regression. MAIN OUTCOME
MEASURES: Very small for gestational age (vSGA; birthweight <=-1.96 standard
deviations) and perinatal death (stillbirth at >=22 weeks of gestation or death
within 28 days of life). RESULTS: Small fetal size at ultrasound (i.e. a fetus
smaller than expected by last menstrual period, LMP) is only weakly predictive of
vSGA or perinatal death; however, if the firstborn sibling was vSGA at birth,
ultrasound measures in the next pregnancy become strongly informative of risk.
The smaller the fetal size on ultrasound, the higher its risk of vSGA (3-18%;
Ptrend < 0.0001) and perinatal death (4-19 per thousand, Ptrend = 0.012). In
contrast, if the first baby was not vSGA, small fetal size on ultrasound is
uninformative. CONCLUSIONS: When the firstborn baby is vSGA, discrepancies
between fetal size on ultrasound and LMP become highly predictive of risk of vSGA
and perinatal mortality in the second-born infant. The value of combining these
routinely collected clinical data has not previously been recognised.
PMID- 25135696
TI - The role of phakic intraocular lens implants in treatment of high-refractive
errors and amblyopia in children.
AB - INTRODUCTION: This article aims to evaluate the role of phakic intraocular lens
(pIOL) implants in the treatment of high-refractive errors and amblyopia in the
pediatric setting. METHODS: A literature search of the PubMed database was
conducted in December 2012 using the keywords: pIOL implants, amblyopia,
pediatric refractive surgery and ametropia, and articles of high or medium
clinical relevance were selected for review. Inclusion criteria were children
aged 0-17 years who had undergone pIOL implantation for the treatment of
refractive errors and/or amblyopia. RESULTS: Multiple studies have shown the
relevancy and effectiveness of pIOL implantation as an alternative surgical
management for highly significant pediatric ametropia in selective patients who
are noncompliant with medical treatment. CONCLUSIONS: In the management of
clinically significant severe pediatric ametropic and/or anisometropic myopia or
hyperopia and in the event of nonadherence to traditional medical treatment,
phakic anterior chamber IOL implantation is currently considered an effective
modality of treatment. Long-term follow-up of pediatric patients following pIOL
implantation is necessary. Future clinical trials are needed to address the
safety and efficacy of the type of and the best time for pIOL implantation in
treatment and/or prevention of amblyopia in children.
PMID- 25135697
TI - Observation of peripheral retina by topical endoscopic imaging method-a
preliminary study.
AB - INTRODUCTION: This study evaluated the usefulness of rigid endoscopy placed on
the corneal surface to observe the peripheral retina. METHODS: The authors
studied 15 eyes in 15 patients (12 men, 3 women; mean age 55.9 years; range 22-74
years) that underwent vitreous surgery at the Department of Ophthalmology at Saga
University Hospital. With patients in a supine position, after topical
anesthesia, an eye cup was placed between the eyelids and filled with
hydroxyethyl cellulose solution and physiologic saline. With a rigid endoscope
placed near the corneal surface, the target areas were then observed and
recorded. The usefulness of rigid endoscopy to observe the peripheral retina was
evaluated based on differences due to lens status and pupil size. RESULTS: In
seven aphakic eyes, irrespective of pupil size, the peripheral retina could be
observed up to the entire ora serrata (all quadrants). In eight eyes implanted
with an intraocular lens, the observable area changed with pupil size and
anterior capsulorrhexis size. CONCLUSION: This technique using rigid endoscopy
was simple to manipulate and useful for observing and recording the peripheral
retina. In particular, in aphakic eyes, irrespective of pupil size, the retina
could be observed to the ora serrata.
PMID- 25135698
TI - Evaluation of retinal nerve fiber layer changes with oral isotretinoin treatment.
AB - INTRODUCTION: Central nervous system toxicity is a well-known side effect of
isotretinoin treatment. The aim of this study was to establish the effects of
isotretinoin on retinal nerve fiber layer (RNFL) thickness. MATERIALS AND
METHODS: Study subjects received oral isotretinoin treatment for nodulocystic
acne. All patients underwent a detailed ophthalmologic examination including best
corrected visual acuity, slit-lamp examination, tonometry, color vision
assessment, fundoscopy, and RNFL measurement. RNFL measurements by optical
coherence tomography were done at onset, and were repeated at the 1st and 6th
months of therapy. RESULTS: A total of 22 eyes of 11 patients (seven males and
four females) were included in this study. The mean age of the patients was 20.18
+/- 5.13 (14-26) years. Mean RNFL thickness was 90.72 +/- 9.19 (78.2-112.0) MUm
before treatment, 90.40 +/- 9.24 (79.5-112.4) MUm after 1 month of treatment, and
90.52 +/- 8.92 (78.4-114.8) MUm after 6 months. No statistically significant
change was detected between RNFL thickness values before and after treatment.
CONCLUSION: No adverse effects of systemic isotretinoin treatment on RNFL
thickness were observed.
PMID- 25135699
TI - Transcorneal electrical stimulation in patients with retinal artery occlusion: a
prospective, randomized, sham-controlled pilot study.
AB - INTRODUCTION: The purpose of this study was to investigate the safety and
efficacy of transcorneal electrical stimulation (TES) in patients suffering from
retinal artery occlusion (RAO). METHODS: Twelve patients with central and one
patient with branch RAO (age 25-84 years, median 74 years) were enrolled in this
prospective, randomized, sham-controlled study. RAO was diagnosed 10 days to 17
months prior to study participation. Patients were treated with TES (5 ms
positive followed by 5 ms negative biphasic pulses at 20 Hz; applied with DTL
electrodes) for 30 min once a week for 6 consecutive weeks. Patients were
randomly assigned to TES with 0 mA (sham, n = 3), 66% (n = 5) or 150% (n = 5) of
the patient's individual electrical phosphene threshold (EPT) at 20 Hz. Best
corrected visual acuity, ophthalmology examination and EPT (at 3, 6, 9, 20, 40,
60, and 80 Hz) were determined at baseline and at eight follow-up visits over 17
weeks. During four visits (week 1, 5, 9, and 17) kinetic and static visual fields
as well as full-field and multifocal electroretinography were measured. The
method of restricted maximum likelihood (P < 0.05, Tukey-Kramer) was used to
estimate the development of parameters under treatment. RESULTS: TES was
tolerated well; no ocular or systemic adverse events were observed except for
foreign-body sensation after TES (n = 3). During the study period the slopes of
the scotopic a-wave increased significantly (high-intensity flash white 10
cd.s/m(2); P = 0.03) in the 150% treatment group. All other parameters in all
other groups remained statistically unchanged. CONCLUSIONS: Although TES was
tolerated well, statistically significant improvements were found only for
specific a-wave slopes. This is in contradiction to previous smaller,
uncontrolled reports. Further studies with larger sample sizes and longer
duration might, however, show additional significant effects.
PMID- 25135701
TI - Erratum to: Topical Isopropyl Unoprostone for Retinitis Pigmentosa:
Microperimetric Results of the Phase 2 Clinical Study.
PMID- 25135700
TI - Vascular endothelial growth factor in anterior chamber liquid patients with
diabetic retinopathy, cataract and neovascular glaucoma.
AB - INTRODUCTION: The aims of this study were: (1) to investigate the association of
vascular endothelial growth factor isoform A (VEGF-A) concentration in the
anterior chamber liquid (ACL) with vascular proliferation in patients with
diabetic retinopathy (DR) who had undergone surgical treatment for cataract and
neovascular glaucoma; (2) to analyze the association of VEGF-A level in ACL with
the cataract surgery outcomes. MATERIALS AND METHODS: Undiluted aqueous fluid
samples were obtained from 207 eyes of patients who underwent intraocular
surgery, 136 patients with diabetes mellitus (DM) and 22 patients without DM. The
ACL samples were obtained during operation. The VEGF-A levels were analyzed by
enzyme-linked immunosorbent assay. RESULTS: The lowest VEGF-A levels were in
diabetic patients without signs of DR [22.75 pg/mL (10.78; 63.36)]. More severe
DR tended to occur in diabetic patients with higher VEGF-A levels in ACL. In
diabetic patients with proliferative DR (PDR), VEGF-A levels were significantly
higher [336.6 pg/mL (232.3; 410.74)] than in patients without DR P < 0.0001. In
patients with terminal stage of DR [neovascular glaucoma (NG)], VEGF-A levels
were dramatically higher and attained 1,634.01 pg/mL (610.69; 2657.33). In non
diabetic patients, VEGF-A levels were 95.07 pg/ml (60.92; 129.22). The best
visual acuity results in post-operative period were observed in the group of
diabetic patients without DR. In the group of patients with PDR, post-operative
visual acuity [0.26 (0.1; 0.42)] was similar to visual acuity before operation
[0.29 (0.13; 0.44)]. There was no significant increase in visual acuity due to
cataract surgery. In 52.4% patients, no complications had occurred by the end of
the follow-up period. In 40% patients, retinal laser coagulation was performed,
and in 7.6% patients NG had developed. CONCLUSION: VEGF-A level in ACL increases
with DR progression and may be of prognostic value in evaluating the potential
risk of further neovascularization progression in diabetic patients.
PMID- 25135702
TI - Screening methodologies for the development of spray-dried amorphous solid
dispersions.
AB - PURPOSE: To present a new screening methodology intended to be used in the early
development of spray-dried amorphous solid dispersions. METHODS: A model that
combines thermodynamic, kinetic and manufacturing considerations was implemented
to obtain estimates of the miscibility and phase behavior of different
itraconazole-based solid dispersions. Additionally, a small-scale solvent casting
protocol was developed to enable a fast assessment on the amorphous stability of
the different drug-polymer systems. Then, solid dispersions at predefined drug
loads were produced in a lab-scale spray dryer for powder characterization and
comparison of the results generated by the model and solvent cast samples.
RESULTS: The results obtained with the model enabled the ranking of the polymers
from a miscibility standpoint. Such ranking was consistent with the experimental
data obtained by solvent casting and spray drying. Moreover, the range of optimal
drug load determined by the model was as well consistent with the experimental
results. CONCLUSIONS: The screening methodology presented in this work showed
that a set of amorphous formulation candidates can be assessed in a computer
model, enabling not only the determination of the most suitable polymers, but
also of the optimal drug load range to be tested in laboratory experiments. The
set of formulation candidates can then be further fine-tuned with solvent casting
experiments using a small amount of API, which will then provide the decision for
the final candidate formulations to be assessed in spray drying experiments.
PMID- 25135703
TI - [Aggravated reduction of the posterior malleolar fracture due to incarceration of
the flexor digitorum longus tendon].
AB - The indications for stabilization of the posterior malleolus (Volkmann triangle)
while fixing ankle fractures are controversially discussed. Detailed descriptions
of possible obstacles to reduction are scarce. The following case describes the
difficulty of reduction of the posterior malleolus caused by interposition of the
flexor digitorum longus tendon. The fracture line of the posterior malleolus
passed in an atypical manner vertically to the posterior-medial tibial margin
with direct contact to the anatomical pathway of the tendon. The impaction of the
tendon was already present in the computed tomography (CT) scan taken
preoperatively but the tendon hindering malleolar reduction was first realized
during surgery after several unsuccessful attempts at repositioning.
PMID- 25135704
TI - [Expectations from the TraumaNetwork DGU(r): Which goals have been achieved? What
can be improved?].
AB - INTRODUCTION: Following the establishment of the first trauma networks in 2009 an
almost nationwide certification could be achieved. Despite the impressive number
of 46 certified networks, little is known about the actual improvements and the
satisfaction of the participating hospitals. OBJECTIVES: This article aims to
give a first representative overview of the expectations and actual achievements.
MATERIAL AND METHODS: An online survey with a total of 36 questions was conducted
in 884 hospitals. The questionnaire could be filled out online, sent by post or
fax to the AKUT- Office. Descriptive statistical analyses were performed with
Microsoft Excel. RESULTS: With 326 responses, a response rate of 48.9% of all
active hospitals was achieved. Of the participating hospitals 64.1% (209) were
certified and had taken part in the project for an average of 3.9 years. The
average score for satisfaction was 2.3, 72.4% (236) felt that there was a need
for improvement in the care of severely injured patients and 46.6% (152) in the
transfer of patients. In 47.2% (142) no improvement in cooperation with the
ambulance service could be determined, 25.2% (82) documented an increase in the
number of severely injured patients since participating in the trauma network
(TNW-DGU) and 93.9% (306) of all hospitals wanted to participate in the trauma
network in the future. DISCUSSION: It could be shown that important goals, such
as simplification of patient transfer or general improvement in cooperation have
been achieved. Overall there was a high level of satisfaction among the
participating hospitals; however, the survey has identified some points which
need to be improved by further intensive work.
PMID- 25135705
TI - [Aseptic acetabular necrosis with recurrent luxation of a bipolar
hemiarthroplasty into the retroperitoneum].
AB - In comparison to aseptic osteonecrosis of the femoral head, the occurrence of
aseptic acetabular osteonecrosis is extremely rare. This article reports the case
of a 77-year-old woman with a large defect of the posterior acetabular wall (type
3 AAOS/D'Antonio score). We present an option for treatment in cases of a
combination of osteonecrosis with implanted bipolar hemiarthroplasty.
PMID- 25135706
TI - [Bilateral carotid artery dissection in a kite surfer by strangulation with the
kite lines].
AB - While a kite surfer was preparing the kite it was caught by a gust of wind, which
blew it 10 m into the air and the cords became entangled around the neck of the
kite surfer causing strangulation. After admittance to hospital, the diagnostics
revealed multiple injuries including a bilateral dissection of the internal
carotid arteries, cerebral edema and multiple fractures. As kitesurfing is
gaining popularity severe injuries are becoming more frequent. Safety
precautions, such as preparing the kite with two persons, wearing safety
equipment and using bars with a safety leash can prevent severe injuries.
PMID- 25135707
TI - [Out-of-hospital airway management in trauma patients : Experiences with the C
MAC(r) video laryngoscope].
AB - BACKGROUND: Securing the airway is the top priority in trauma resuscitation. The
most important factor for successful endotracheal intubation (ETI) is good
visualization of the vocal cords. The aim of this study was to summarize the
practical experiences with the C-MAC(r) video laryngoscope as initial device in
out-of-hospital airway management of trauma patients. METHODS: The C-MAC(r) video
laryngoscope uses standard Macintosh shaped laryngoscope blades. At the
Helicopter Emergency Medical Service (HEMS) Christoph 22 it is used as the
initial device for every out-of-hospital ETI. All prehospital data on ETI
involving trauma patients were documented for a period of 17 months. RESULTS: A
total of 116 out-of-hospital ETIs were enrolled in this study (overall success
rate 100 %). In 88.8 % the first attempt was successful, whereas in 10.3 % a
second and in 0.9 % a third ETI attempt was necessary. No patient required
alternative airway devices or surgical airway interventions. The results of a
subgroup with an immobilized cervical spine (n = 17) did not show any increased
difficulties. CONCLUSION: The use of the C-MAC(r) video laryngoscope by
experienced anesthesiologists in an out-of-hospital setting seems to be a safe
method even in patients with an immobilized cervical spine. Adverse laryngoscopy
results (C/L III and IV) were reduced compared to other studies.
PMID- 25135710
TI - A scoping review of time-use research in occupational therapy and occupational
science.
AB - BACKGROUND: Time use is a defining interest within occupational therapy and
occupational science. This is evident through the range of contributions to the
disciplinary knowledge base. Indeed it has been suggested that time-use methods
are amongst the most established research techniques used to explore aspects of
human occupation. However, the extent and nature of such activity in occupational
therapy and occupational science has not been examined to date. AIM: This study
sought to map the extent and nature of time-use research in occupational therapy
and occupational science journals and the extent to which studies explored the
relationship between time-use and health. METHOD: A scoping review method was
used. RESULTS: Sixty-one studies were included. Scandinavian countries
contributed the largest number of studies (n = 16, 26%). While time-use diaries
were used most frequently (n = 30, 49%) occupational therapists and occupational
scientists have developed a range of data-collection instruments. Forty-nine
studies (80%) focused on time-use in clinical or defined population sub-groups.
Ten studies (16%) included an empirical examination of the relationship between
time-use and health. CONCLUSION: Future research should examine time-use and
health amongst well populations across the lifespan and in different parts of the
world.
PMID- 25135708
TI - Hesperidin alleviates cognitive impairment, mitochondrial dysfunction and
oxidative stress in a mouse model of Alzheimer's disease.
AB - The role of mitochondrial dysfunction and oxidative stress has been well
documented in Alzheimer's disease (AD). Bioflavonoids are being utilised as
neuroprotectants in the treatment of various neurological disorders, including
AD. Therefore, we conducted this current study in order to explore the effects of
hesperidin (a flavanone glycoside) against amyloid-beta (Abeta)-induced cognitive
dysfunction, oxidative damage and mitochondrial dysfunction in mice. Three-month
old APPswe/PS1dE9 transgenic mice were randomly assigned to a vehicle group, two
hesperidin (either 50 or 100 mg/kg per day) groups, or an Aricept (2.5 mg/kg per
day) group. After 16 weeks of treatment, although there was no obvious change in
Abeta deposition in the hesperidin-treated (100 mg/kg per day) group, however, we
found that the administration of hesperidin (100 mg/kg per day) resulted in the
reduction of learning and memory deficits, improved locomotor activity, and the
increase of anti-oxidative defense and mitochondrial complex I-IV enzymes
activities. Furthermore, Glycogen synthase kinase-3beta (GSK-3beta)
phosphorylation significantly increased in the hesperidin-treated (100 mg/kg per
day) group. Taken together, these findings suggest that a reduction in
mitochondrial dysfunction through the inhibition of GSK-3beta activity, coupled
with an increase in anti-oxidative defense, may be one of the mechanisms by which
hesperidin improves cognitive function in the APPswe/PS1dE9 transgenic mouse
model of AD.
PMID- 25135709
TI - Inhibition of akt phosphorylation diminishes mitochondrial biogenesis regulators,
tricarboxylic acid cycle activity and exacerbates recognition memory deficit in
rat model of Alzheimer's disease.
AB - 3-Methyladenine (3-MA), as a PI3K inhibitor, is widely used for inhibition of
autophagy. Inhibition of PI3K class I leads to inhibition of Akt phosphorylation,
a central molecule involved in diverse arrays of intracellular cascades in
nervous system. Accordingly, in the present study, we aimed to determine the
alterations of specific mitochondrial biogenesis markers and mitochondrial
function in 3-MA-injected rats following amyloid beta (Abeta) insult. Our data
revealed that inhibition of Akt phosphorylation downregulates master regulator of
mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma
coactivator 1-alpha (PGC-1alpha). Our data also showed that decrease in PGC
1alpha level presumably is due to decrease in the phosphorylation of cAMP
response element binding and AMP-activated kinase, two upstream activators of PGC
1alpha. As a consequence, the level of some mitochondrial biogenesis factors
including nuclear respiratory factor-1, mitochondrial transcription factor A, and
Cytochrome c decreased significantly. Also, activities of tricarboxylic acid
cycle (TCA) enzymes such as Aconitase, a-ketoglutarate dehydrogenase, and malate
dehydrogenase reduced in the presence of 3-MA with or without Abeta insult.
Decrease in mitochondrial biogenesis factors and TCA enzyme activity in the rats
receiving 3-MA and Abeta were more compared to the rats that received either
alone; indicating the additive destructive effects of these two agents. In
agreement with our molecular results, data obtained from behavioral test (using
novel objective recognition test) indicated that inhibition of Akt
phosphorylation with or without Abeta injection impaired novel recognition (non
spatial) memory. Our results suggest that 3-MA amplified deleterious effects of
Abeta by targeting central molecule Akt.
PMID- 25135711
TI - Comparison of diagnostic performance of CT and MRI for abdominal staging of
pediatric renal tumors: a report from the Children's Oncology Group.
AB - BACKGROUND: CT and MRI are both used for abdominal staging of pediatric renal
tumors. The diagnostic performance of the two modalities for local and regional
staging of renal tumors has not been systematically evaluated. OBJECTIVE: To
compare the diagnostic performance of CT and MRI for local staging of pediatric
renal tumors. MATERIALS AND METHODS: The study population was derived from the
AREN03B2 study of the Children's Oncology Group. Baseline abdominal imaging
performed with both CT and MRI within 30 days of nephrectomy was available for
retrospective review in 82 renal tumor cases. Each case was evaluated for
capsular penetration, lymph node metastasis, tumor thrombus, preoperative tumor
rupture, and synchronous contralateral lesions. The surgical and pathological
findings at central review were the reference standard. RESULTS: The sensitivity
of CT and MRI for detecting capsular penetration was 68.6% and 62.9%,
respectively (P = 0.73), while specificity was 86.5% and 83.8% (P = 1.0). The
sensitivity of CT and MRI for detecting lymph node metastasis was 76.5% and 52.9%
(P = 0.22), and specificity was 90.4% and 92.3% (P = 1.0). Synchronous
contralateral lesions were identified by CT in 4/9 cases and by MRI in 7/9 cases.
CONCLUSION: CT and MRI have similar diagnostic performance for detection of lymph
node metastasis and capsular penetration. MR detected more contralateral
synchronous lesions; however these were present in a very small number of cases.
Either modality can be used for initial loco-regional staging of pediatric renal
tumors.
PMID- 25135712
TI - Decolonization with Mupirocin and Subsequent Risk of Methicillin-Resistant
Staphylococcus aureus Carriage in Veterans Affairs Hospitals.
AB - INTRODUCTION: Hospital-acquired methicillin-resistant Staphylococcus aureus
(MRSA) infections remain one of the leading causes of preventable patient
mortality in the US. Eradication of MRSA through decolonization could prevent
both MRSA infections and transmission; however, there is currently no consensus
within the infectious disease community on the proper role of decolonization in
the prevention of infections. The purpose of this study was to assess the impact
of decolonization with mupirocin on subsequent MRSA carriage. METHODS: Patients
included in this study were those with an inpatient admission to a Department of
Veterans Affairs (VA) hospital between January 1, 2008 and December 31, 2009 who
had a positive MRSA screen on admission and a subsequent re-admission during the
same time period. Exposure to mupirocin on the initial hospital admission was
measured using Barcode Medication Administration data and MRSA carriage was
measured using microbiology text reports and lab data containing results from
surveillance swabs collected from the nares. Chi-square tests were used to test
for differences in re-admission MRSA carriage rates between mupirocin-receiving
and non-mupirocin-receiving patients. RESULTS: Of the 25,282 MRSA-positive
patients with a subsequent re-admission included in the present study cohort,
1,183 (4.7%) received mupirocin during their initial hospitalization. Among the
patients in the present study cohort who were re-admitted within 30 days, those
who received mupirocin were less likely to test positive for MRSA carriage than
those who did not receive mupirocin (27.2% vs. 55.1%, P < 0.001). The proportion
of those who tested positive for MRSA during re-admissions that occurred 30-60
days, 60-120 days, and >120 days were 33.9, 37.3, and 41.0%, respectively, among
mupirocin patients and 52.7%, 53.0%, and 51.9%, respectively, for patients who
did not receive mupirocin (P < 0.001 at each time point). CONCLUSION: Patients
decolonized with mupirocin in VA hospitals were less likely to be colonized with
MRSA on re-admission as long as 4 months after decolonization.
PMID- 25135714
TI - Effect of uric-acid-lowering therapy on progression of chronic kidney disease: a
meta-analysis.
AB - The efficacy and safety of uric-acid-lowering therapy (UALT) on slowing the
progression of chronic kidney disease (CKD) accompanied by hyperuricemia were
assessed. We searched Cochrane Library, PubMed, EMbase, CNKI, Wanfang and Vip
databases up to November 15, 2012 for randomized controlled trials (RCTs) which
compared the effect of UALT to control therapy in hyperuricemic patients
secondary to CKD, and then performed quality evaluation and meta-analysis on the
included studies. Seven RCTs involving 451 cases were included. UALT delayed the
increase of serum creatinine (MD=-62.55 MUmol/L, 95% CI: -98.10 to -26.99) and
blood urea nitrogen (MD= -6.15 mmol/L, 95% CI: -8.17 to -4.13) as well as the
decrease of glomerular filtration rate [MD=5.65 mL/(min.1.73 m2), 95% CI: 1.88 to
9.41], decreased systolic blood pressure (SBP) (MD= -6.08 mmHg, 95% CI: -11.67 to
-0.49), and reduced the risk of the renal disease progression (RR=0.30, 95% CI:
0.19 to 0.46). However, there was no statistically significant difference in 24-h
urinary protein quantity and diastolic blood pressure (P>0.05). We identified
that UALT could delay the progression of CKD with secondary hyperuricemia. And
this also indirectly proved that hyperuricemia was a risk factor for the CKD
progression.
PMID- 25135713
TI - Diagnosis and treatment of cholangiocarcinoma: a consensus from surgical
specialists of China.
PMID- 25135716
TI - Expression and clinical significance of Semaphorin4D in non-small cell lung
cancer and its impact on malignant behaviors of A549 lung cancer cells.
AB - This study aimed to explore Semaphrin4D (Sema4D) expression and clinical
significance in non-small cell lung cancer (NSCLC), and to define the roles and
mechanisms of Sema4D in regulating the malignant behaviors of A549 cells by small
interfering RNA (siRNA). Firstly, immunohistochemistry revealed that Sema4D was
more frequently expressed in NSCLC than in lung benign lesion (P<0.05) and its
overexpression was associated with low differentiation (P<0.05), poor pTNM
staging (P<0.05) and occurrence of lymph node (LN) metastasis (P<0.05).
Endogenous Sema4D expression was suppressed by Sema4D siRNA in A549 cells
overexpressing Sema4D. Protein levels of Sema4D, total Akt and p-Akt were
examined by Western blotting. Cell proliferation, migration and invasion
abilities were measured by MTT assay and Transwell assay respectively. Results
showed that Sema4D siRNA significantly suppressed phosphorylation of AKT in A549
cells, but it did not alter total AKT expression. In addition, efficient down
regulation of SemaD significantly inhibit cell proliferation (P<0.05), migration
(P<0.05) and invasion (P<0.05) in A549 cells. These findings suggest that Sema4D
might serve as a reliable tool for early prediction of NSCLC poor prognosis.
Sema4D could play an important role in promoting tumor proliferation, migration
and metastasis in the NSCLC, by influencing the Akt protein phosphorylation.
Inhibition of Sema4D may be a useful approach for the treatment of NSCLC.
PMID- 25135715
TI - Differential effect of calcium-activated potassium and chloride channels on rat
basilar artery vasomotion.
AB - Spontaneous, rhythmical contractions, or vasomotion, can be recorded from
cerebral vessels under both normal physiological and pathophysiological
conditions. We investigated the cellular mechanisms underlying vasomotion in the
cerebral basilar artery (BA) of Wistar rats. Pressure myograph video microscopy
was used to study the changes in cerebral artery vessel diameter. The main
results of this study were as follows: (1) The diameters of BA and middle
cerebral artery (MCA) were 314.5+/-15.7 MUm (n=15) and 233.3+/-10.1 MUm (n=12) at
10 mmHg working pressure (P<0.05), respectively. Pressure-induced vasomotion
occurred in BA (22/28, 78.6%), but not in MCA (4/31, 12.9%) from 0 to 70 mmHg
working pressure. As is typical for vasomotion, the contractile phase of the
response was more rapid than the relaxation phase; (2) The frequency of
vasomotion response and the diameter were gradually increased in BA from 0 to 70
mmHg working pressure. The amplitude of the rhythmic contractions was relatively
constant once stable conditions were achieved. The frequency of contractions was
variable and the highest value was 16.7+/-4.7 (n=13) per 10 min at 60 mmHg
working pressure; (3) The pressure-induced vasomotion of the isolated BA was
attenuated by nifedipine, NFA, 18beta-GA, TEA or in Ca(2+)-free medium.
Nifedipine, NFA, 18beta-GA or Ca(2+)-free medium not only dampened vasomotion,
but also kept BA in relaxation state. In contrasts, TEA kept BA in contraction
state. These results suggest that the pressure-induced vasomotion of the isolated
BA results from an interaction between Ca(2+)-activated Cl(-) channels (CaCCs)
currents and K(Ca) currents. We hypothesize that vasomotion of BA depends on the
depolarizing of the vascular smooth muscle cells (VSMCs) to activate CaCCs.
Depolarization in turn activates voltage-dependent Ca(2+) channels, synchronizing
contractions of adjacent cells through influx of extracellular calcium and the
flow of calcium through gap junctions. Subsequent calcium-induced calcium release
from ryanodine-sensitive stores activates K(Ca) channels and hyperpolarizes
VSMCs, which provides a negative feedback loop for regenerating the contractile
cycle.
PMID- 25135717
TI - Anticancer effect of icaritin on human lung cancer cells through inducing S phase
cell cycle arrest and apoptosis.
AB - Icaritin, a prenylflavonoid derivative from Epimedium Genus, has been shown to
exhibit many pharmacological and biological activities. However, the function and
the underlying mechanisms of icaritin in human non-small cell lung cancer have
not been fully elucidated. The purpose of this study was to investigate the
anticancer effects of icaritin on A549 cells and explore the underlying molecular
mechanism. The cell viability after icaritin treatment was tested by MTT assay.
The cell cycle distribution, apoptosis and reactive oxygen species (ROS) levels
were analyzed by flow cytometry. The mRNA and protein expression levels of the
genes involved in proliferation and apoptosis were respectively detected by RT
PCR and Western blotting. The results demonstrated that icaritin induced cell
cycle arrest at S phase, and down-regulated the expression levels of S regulatory
proteins such as Cyclin A and CDK2. Icaritin also induced cell apoptosis
characterized by positive Hoechst 33258 staining, accumulation of the Annexin V
positive cells, increased ROS level and alteration in Bcl-2 family proteins
expression. Moreover, icaritin induced sustained phosphorylation of ERK and p38
MAPK. These findings suggested that icaritin might be a new potent inhibitor by
inducing S phase arrest and apoptosis in human lung carcinoma A549 cells.
PMID- 25135718
TI - Effect of TRPV1 channel on proliferation and apoptosis of airway smooth muscle
cells of rats.
AB - Airway remodeling is an important pathological feature of asthma and the basis of
severe asthma. Proliferation of airway smooth muscle cells (ASMCs) is a major
contributor to airway remodeling. As an important Ca(2+) channel, transient
receptor potential vanilloid 1 (TRPV1) plays the key role in the cell
pathological and physiological processes. This study investigated the expression
and activity of TRPV1 channel, and further clarified the effect of TRPV1 channel
on the ASMCs proliferation and apoptosis in order to provide the scientific basis
to treat asthmatic airway remodeling in clinical practice. Immunofluorescence
staining and reverse transcription polymerase chain reaction (RT-PCR) were used
to detect the expression of TRPV1 in rat ASMCs. Intracellular Ca(2+) was detected
using the single cell confocal fluorescence microscopy measurement loaded with
Fluo-4/AM. The cell cycles were observed by flow cytometry. MTT assay and Hoechst
33258 staining were used to detect the proliferation and apoptosis of ASMCs in
rats respectively. The data showed that: (1) TRPV1 channel was present in rat
ASMCs. (2) TRPV1 channel agonist, capsaicin, increased the Ca(2+) influx in a
concentration-dependent manner (EC50=284.3+/-58 nmol/L). TRPV1 channel
antagonist, capsazepine, inhibited Ca(2+) influx in rat ASMCs. (3) Capsaicin
significantly increased the percentage of S+G2M ASMCs and the absorbance of MTT
assay. Capsazepine had the opposite effect. (4) Capsaicin significantly inhibited
the apoptosis, whereas capsazepine had the opposite effect. These results suggest
that TRPV1 is present and mediates Ca(2+) influx in rat ASMCs. TRPV1 activity
stimulates proliferation of ASMCs in rats.
PMID- 25135719
TI - Changes of neuronal activities after gut electrical stimulation with different
parameters and locations in lateral hypothalamus area of obese rats.
AB - This study tested the effects of the gastrointestinal pulse train electrical
stimulation with different parameters and at different locations on the neuronal
activities of the lateral hypothalamus area (LHA) in obese rats in order to find
the optimal stimulation parameter and location. Eight gastric electrical
stimulations (GES) with different parameters were performed and the neuronal
activities of gastric-distension responsive (GD-R) neurons in LHA were observed.
The effects of stimulations with 8 parameters were compared to find the optimal
parameter. Then the optimal parameter was used to perform electrical stimulation
at duodenum and ileum, and the effects of the duodenal and ileac stimulation on
the GD-R neurons in LHA were compared with the gastric stimulation of optimal
parameter. The results showed that GES with the lowest energy parameter (0.3 ms,
3 mA, 20 Hz, 2 s on, 3 s off) activated the least neurons. The effects of GES
with other parameters whose pulse width was 0.3 ms were not significantly
different from those of the lowest energy parameter. Most gastric stimulations
whose pulse width was 3 ms activated more LHA neurons than the smallest energy
parameter stimulation, and the effects of those 3 ms gastric stimulations were
similar. Accordingly, the lowest energy parameter was recognized as the optimal
parameter. The effects of stimulations with the optimal parameter at stomach,
duodenum and ileum on the LHA neuronal activities were not different.
Collectively, gastrointestinal electrical stimulation (GIES) with relatively
large pulse width might have stronger effects to the neuronal activities of GD-R
neurons in LHA of obese rats. The effects of the GIES at different locations
(stomach, duodenum and ileum) on those neurons are similar, and GES is
preferential because of its easy clinical performance and safety.
PMID- 25135720
TI - Glucocorticoid receptor agonist dexamethasone attenuates renal
ischemia/reperfusion injury by up-regulating eNOS/iNOS.
AB - The aim of this study was to determine the effect of dexamethasone (DEX) on renal
ischemia/reperfusion injury (IRI). C57BL/6 mice were randomly divided into Sham
group, IRI group and DEX group. The mice in IRI and DEX groups subjected to renal
ischemia for 60 min, were treated with saline or DEX (4 mg/kg, i.p.) 60 min prior
to I/R. After 24 h of reperfusion, the renal function, renal pathological
changes, activation of extracellular signal-regulated kinase (ERK) and
glucocorticoid receptor (GR), and the levels of iNOS and eNOS were detected. The
results showed DEX significantly decreased the damage to renal function and
pathological changes after renal IRI. Pre-treatment with DEX reduced ERK
activation and down-regulated the level of iNOS, whereas up-regulated the level
of eNOS after renal IRI. DEX could further promote the activation of GR. These
findings indicated GR activation confers preconditioning-like protection against
acute IRI partially by up-regulating the ratio of eNOS/iNOS.
PMID- 25135721
TI - Anti-cancer effects of novel doxorubicin prodrug PDOX in MCF-7 breast cancer
cells.
AB - Ac-Phe-Lys-PABC-DOX (PDOX) is a smart doxorubicin (DOX) prodrug designed to
decrease toxicities while maintaining the potent anticancer effects of DOX. This
study was aimed at elucidating the effectiveness and toxicities of DOX and PDOX
in patient-derived MCF-7 breast cancer cells in vitro. The MCF-7 cells were
exposed to both PDOX and DOX, and cytotoxicities, cell cycle and P53/P21
signaling alterations were studied. Abundant cathepsin B was found in the MCF-7
cells, and treatment with PDOX and DOX triggered dose- and time-dependent
cytotoxicity and resulted in a significant reduction in cell viability. The IC50
of PDOX and DOX was 3.91 and 0.94 MUmol/L, respectively. Both PDOX and DOX caused
an up-regulation of the P53/P21-related signal pathway, and PDOX significantly
increased expression of P53 and caspase 3, and arrested the cell cycle at the
G1/G2 phase. As compared with DOX, PDOX reduced toxicities, and it may have
different action mechanisms on breast cancer cells.
PMID- 25135722
TI - Antitumor activity of recombinant antimicrobial peptide penaeidin-2 against
kidney cancer cells.
AB - Penaeidin-2 (Pen-2) is an important antimicrobial peptide derived from the
Pacific white shrimp, Penaeus vannamei, and possesses both antibacterial and
antifungal activities. Recent studies suggest that recombinant penaeidins show
similar activities to the native Pen-2 protein. Previous researches have shown
that some antimicrobial peptides (AMPs) exhibit cytotoxic activity against cancer
cells. To date, there have been no studies on the antitumor effects of Pen-2.
This study evaluated the potential of recombinant pen-2 (rPen-2) in the selective
killing of kidney cancer cell lines ACHN and A498, and its action mechanism. MTT
assays found the maximal growth inhibition of HK-2, ACHN and A498 cells treated
with 100 MUg/mL rPen-2 at 48 h was 13.2%, 62.4%, and 70.4%, respectively. DNA
specific fluorescent dye staining showed a high percentage of apoptosis on cancer
cells. Flow cytometry revealed that the apoptosis rate of HK-2, ACHN and A498
cells was 15.2%, 55.2%, and 61.5% at 48 h respectively, suggesting that rPen-2
induced higher apoptosis rate in cancer cells than in HK-2 cells. Laser confocal
scanning microscopy demonstrated that the plasma membrane was the key site where
rPen-2 interacted with and destroyed tumor cells. Scanning electron microscopy
showed the morphologic changes of the cell membranes of kidney cancer cells
treated with rPen-2. These results suggest that rPen-2 is a novel potential
therapeutic agent that may be useful in treating kidney cancers.
PMID- 25135724
TI - Combination therapy with pegylated interferon alpha-2b and adefovir dipivoxil in
HBeAg-positive chronic hepatitis B versus interferon alone: a prospective,
randomized study.
AB - Currently available monotherapies of oral nucleoside/nucleotide analogs or
interferon are unable to achieve a sustained and effective response in most of
patients with chronic hepatitis B (CHB). The objective of the present study was
to compare the efficacy and safety of pegylated interferon (Peg-IFN) alpha-2b
plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty
one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg
IFN alpha-2b alone (1.5 MUg/kg once weekly) or Peg-IFN alpha-2b plus adefovir (10
mg daily) for up to 52 weeks. Efficacy and safety analyses were performed on all
participants who received at least one dose of study medication. The rate of
HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of
therapy. At the end of treatment, 11 of 30 (36.7%) patients receiving combination
therapy achieved HBeAg seroconversion versus 8 of 31 (25.8%) in the monotherapy
group (P=0.36). In contrast, the percentage of patients with undetectable serum
HBV DNA was significantly higher in the combination group than in the monotherapy
group (76.7% vs. 29.0%, P<0.001). Thyroid dysfunction was more frequent in the
combination group than in the monotherapy group (P<0.05). In HBeAg-positive CHB,
combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of
treatment, in a higher virological response but without significant impact on the
rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.
PMID- 25135723
TI - Over-expression of testis-specific expressed gene 1 attenuates the proliferation
and induces apoptosis of GC-1spg cells.
AB - The effects of over-expression of testis-specific expressed gene 1 (TSEG-1) on
the viability and apoptosis of cultured spermatogonial GC-1spg cells were
investigated, and the immortal spermatogonial cell line GC-1spg (CRL-2053TM) was
obtained as the cell model in order to explore the function of TSEG-1. We
transfected the eukaryotic vector of TSEG-1, named as pEGFP-TSEG-1 into cultured
spermatogonial GC-1spg cells. Over-expression of TSEG-1 inhibited the
proliferation of GC-1spg cells, and arrested cell cycle slightly at G0/G1 phase.
Transfection of TSEG-1 attenuated the transcript levels of Ki-67, PCNA and cyclin
D1. In addition, over-expression of TSEG-1 induced early and late apoptosis, and
reduced the mitochondrial membrane potential of GC-1spg cells. Moreover,
transfection of TSEG-1 significantly enhanced the ratio of Bax/Bcl-2 and
transcript levels of caspase 9, and decreased the expression of Fas and caspase 8
in GC-1spg cells. These results indicated over-expression of TSEG-1 suppresses
the proliferation and induces the apoptosis of GC-1spg cells, which establishes a
basis for further study on the function of TSEG-1.
PMID- 25135725
TI - Expression profiling of microRNAs in hippocampus of rats following traumatic
brain injury.
AB - The changes of microRNA expression in rat hippocampus after traumatic brain
injury (TBI) were explored. Adult SD rats received a single controlled cortical
impact injury, and the ipsilateral hippocampus was harvested for the subsequent
microarray assay at three time points after TBI: 1st day, 3rd day and 5th day,
respectively. We characterized the microRNA expression profile in rat hippocampus
using the microRNA microarray analysis, and further verified microarray results
of miR-142-3p and miR-221 using quantitative real-time PCR. Totally 205 microRNAs
were identified and up-/down-regulated more than 1.5 times. There were
significant changes in 17 microRNAs at all three time points post-TBI. The
quantitative real-time PCR results of miR-142-3p and miR-221 indicated good
consistency with the results of the microarray method. MicroRNAs altered at
different time points post-TBI. MiR-142-3p and miR-221 may be used as potentially
biological markers for TBI assessment in forensic practice.
PMID- 25135726
TI - E-cadherin-transfected neural stem cells transplantation for spinal cord injury
in rats.
AB - The effects of E-cadherin-transfected neural stem cells (NSCs) transplantation
for spinal cord injury (SCI) in rats were investigated. Sixty SD rats were
randomly divided into model control group, NSCs group, empty plasmid group and E
cadherin overexpression group (n=15 each). The animal SCI model was established
by using the modified Allen's method. NSCs were cultured. Rats in NSCs group were
subjected to NSCs transplantation. E-cadherin gene eucaryotic expression vector
and pcDNA3.1-E-cadherin were respectively transfected into cultured NSCs, serving
as empty plasmid group and E-cadherin overexpression group respectively. At 7th
day after transplantation, neurological function of all rats was assessed by
Tarlov score. After rats were sacrificed in each group, the number of BrdU and
Nestin positive cells was counted by immunohistochemistry. Immumofluorescence
method was used to detect the expression of neurofilament protein (NF) and glial
fibrillary acidic protein (GFAP). As compared with model control group, the
Tarlov score and the number of of BrdU and Nestin positive cells, and the
expression of NF and GFAP in NSCs group, empty plasmid group, and E-cadherin
overexpression group were increased significantly (P<0.05), and those in the E
cadherin overexpression group were increased more significantly than the other
transplantation groups (P<0.05). It was suggested that E-cadherin could be
conductive to nerve regeneration and repair probably by promoting the
proliferation and differentiation of NSCs.
PMID- 25135727
TI - Predictors of catheter-related bladder discomfort after urological surgery.
AB - The aim of this study was to figure out the predictors of early postoperative
catheter-related bladder discomfort (CRBD) after urological surgery. We designed
a prospective observational study in our hospital. Consecutive adult patients
undergoing surgery under general anaesthesia or epidural anaesthesia
necessitating urinary catheterization were included during a 3-month period.
severity of bladder discomfort was assessed on a 4-point scale: (1) no pain, (2)
mild pain (revealed only by interviewing the patient), (3) moderate (a
spontaneous complaint by the patient of a burning sensation in the urethra and/or
an urge to urinate and/or sensation of urethral foreign body without any
emotional agitation) and (4) severe discomfort (agitation, loud complaints and
attempt to remove the bladder catheter associated with a burning sensation in the
urethra). Predictors of CRBD were identified by univariate and multivariate
analysis. Totally, 116 patients were included, of which 84.5% had CRBD (mild
CRBD: 40.5%; moderate or severe CRBD: 44.0%) at day 1, while 31.9% developed CRBD
(mild CRBD: 29.3%; moderate or severe CRBD: 2.6%) at day 3. We evaluated 9
potential forecast factors of CRBD, and univariate Chi-square test showed male
gender [OR=2.4, 95%CI (1.1-5.6), P<0.05], abdominal open surgery compared with
transurethral surgery [OR=0.3, 95%CI (0.1-0.6), P<0.05], abdominal surgery
compared with laparoscopic surgery [OR=3.3, 95%CI (1.2-8.9), P<0.05] and history
of catheterization [OR=0.5, 95%CI (0.2-0.9), P<0.05] were independent predictors
of moderate or severe CRBD in the patients after surgery. While multivariate
logistic regression analysis showed that the abdominal open surgery
[EXP(B)=3.074, 95%CI (1.3-7.4), P<0.05] and the history of catheterization
[EXP(B)=2.458, 95%CI (1.1-5.9), P<0.05] might contribute more to the occurrence
of moderate or severe CRBD. In conclusion, this observational study identified
that the type of surgery and the history of catheterization might be predictive
factors of moderate and severe CRBD after urological surgery.
PMID- 25135728
TI - A prospective randomized trial of selective versus nonselective esophagogastric
devascularization for portal hypertension.
AB - Cirrhosis with portal hypertension is a common disease which has a significant
impact on the quality of patients' life. Esophagogastric devascularization (EGDV)
has been demonstrated to be an effective method to treat portal hypertension,
however certain complications are associated with it. The purpose of this study
was to evaluate the effectiveness and clinical outcome of the selective EGDV
(sEGDV) for the treatment of portal hypertension. The study was conducted
prospectively from Jan. 1 2011 to Dec. 31, 2012, and 180 patients were randomized
to the sEGDV group (n=90) or the non-sEGDV (n-sEGDV) group (n=90). Patients'
demographics, preoperative lab test results and operative details were comparable
between the two groups. Postoperative and short-term complications were analyzed
in two groups. There was statistically significant difference (P<0.01) in the PVF
reduction between the two groups. Post-operative complications showed no
statistically significant difference between the two groups in the incidence of
bleeding, ascites, acute portal vein thrombosis, fever and hepatic
encephalopathy. Mortality between two groups was comparable. The incidence of
splenic fossa effusion after the surgery was lower in sEGDV group than in n-sEGDV
group. There were no significant differences in the short-term follow-up data
such as esophageal varices and portal hypertensive gastropathy (P>0.05). It is
suggested that sEGDV is a safe, simple and effective surgical procedure. It has
both the advantages of the shunt and devascularization because it preserves
body's voluntary diversion. With the advantage of low incidence of postoperative
complications, it is an ideal surgical approach for the treatment of portal
hypertension.
PMID- 25135729
TI - Effect of electro-acupuncture stimulation of Ximen (PC4) and Neiguan (PC6) on
remifentanil-induced breakthrough pain following thoracal esophagectomy.
AB - The clinical analgesic effect of electro-acupuncture (EA) stimulation (EAS) on
breakthrough pain induced by remifentanil in patients undergoing radical thoracic
esophagectomy, and the mechanisms were assessed. Sixty patients (ASAIII)
scheduled for elective radical esophagectomy were randomized into three groups:
group A (control) receiving a general anesthesia only; group B (sham) given EA
needles at PC4 (Ximen) and PC6 (Neiguan) but no stimulation; and group C (EAS)
electrically given EAS of the ipsilateral PC4 and PC6 throughout the surgery. The
EAS consisting of a disperse-dense wave with a low frequency of 2 Hz and a high
frequency of 20 Hz, was performed 30 min prior to induction of general anesthesia
and continued through the surgery. At the emergence, sufentanil infusion was
given for postoperative analgesia with loading dose of 7.5 MUg, followed by a
continuous infusion of 2.25 MUg/h. The patient self-administration of sufentanil
was 0.75 MUg with a lockout of 15 min as needed. Additional breakthrough pain was
treated with dezocine (5 mg) intravenously at the patient's request. Blood
samples were collected before (T1), 2 h (T2), 24 h (T3), and 48 h (T4) after
operation to measure the plasma beta-EP, PGE2, and 5-HT. The operative time, the
total dose of sufentanil and the dose of self-administration, and the rescue
doses of dezocine were recorded. Visual Analogue Scale (VAS) scores at 2, 12, 24
and 48 h postoperatively and the incidence of apnea and severe hypotension were
recorded. The results showed that the gender, age, weight, operative time and
remifentanil consumption were comparable among 3 groups. Patients in EAS group
had the lowest VAS scores postoperatively among the three groups (P<0.05). The
total dose of sufentanil was 115+/-6.0 MUg in EAS group, significantly lower than
that in control (134.3+/-5.9 MUg) and sham (133.5+/-7.0 MUg) groups. Similarly,
the rescue dose of dezocine was the least in EAS group (P<0.05) among the three
groups. Plasma beta-EP levels in EAS group at T3 (176.90+/-45.73) and T4
(162.96+/-35.00 pg/mL) were significantly higher than those in control (132.33+/
36.75 and 128.79+/-41.24 pg/mL) and sham (136.56+/-45.80 and 129.85+/-36.14
pg/mL) groups, P<0.05 for all. EAS could decrease the release of PGE2. Plasma
PGE2 levels in EAS group at T2 and T3 (41+/-5 and 40+/-5 pg/mL respectively) were
significantly lower than those in control (64+/-5 and 62+/-7 pg/mL) and sham
(66+/-6 and 62+/-6 pg/mL) groups. Plasma 5-HT levels in EAS group at T2 (133.66+/
40.85) and T3 (154.66+/-52.49 ng/mL) were significantly lower than those in
control (168.33+/-56.94 and 225.28+/-82.03) and sham (164.54+/-47.53 and 217.74+/
76.45 ng/mL) groups. For intra-group comparison, plasma 5-HT and PGE2 levels in
control and sham groups at T2 and T3, and beta-EP in EAS group at T3 and T4 were
significantly higher than those at T1 (P<0.05); PGE2 and 5-HT levels in EAS group
showed no significant difference among the different time points (P>0.05). No
apnea or severe hypotension was observed in any group. It was concluded that
intraoperative ipsilateral EAS at PC4 and PC6 provides effective postoperative
analgesia for patients undergoing radical esophagectomy with remifentanil
anesthesia and significantly decrease requirement for parental narcotics. The
underlying mechanism may be related to stimulation of the release of endogenous
beta-EP and inhibition of inflammatory mediators (5-HT and PGE2).
PMID- 25135731
TI - Analysis of clinical features of painless aortic dissection.
AB - The clinical characteristics of painless aortic dissection were investigated in
order to improve the awareness of diagnosis and treatment of atypical aortic
dissection. The 482 cases of aortic dissection were divided into painless group
and pain group, and the data of the two groups were retrospectively analyzed. The
major clinical symptom was pain in 447 cases (92.74%), while 35 patients (7.26%)
had no typical pain. The gender, age, hypertension, hyperlipidemia, diabetes,
smoking and drinking history had no statistically significant differences between
the two groups (P>0.05). The proportion of Stanford type A in painless group was
significantly higher than that in pain group (48.57% vs. 21.03%, P=0.006). The
incidence of unconsciousness in the painless group was significantly higher than
that in the pain group (14.29% vs. 3.58%, P=0.011). The incidence of hypotension
in painless group was significantly higher than that in pain group for 4.26 folds
(P=0.01). Computed tomography angiography (CTA) examination revealed that the
incidence of aortic arch involved in the painless group was significantly higher
than that in the pain group (19.23% vs. 5.52%, P=0.019). It was concluded that
the incidence of painless aortic dissection was higher in Stanford A type
patients, commonly seen in the patients complicated with hypotension and
unconsciousness. CTA examination revealed higher incidence of aortic arch
involvement.
PMID- 25135730
TI - Renovascular morphological changes in a rabbit model of hydronephrosis.
AB - Obstructive nephropathy ultimately leads to end-stage renal failure. Renovascular
lesions are involved in various nephropathies, and most renal diseases have an
ischemic component that underlies the resulting renal fibrosis. The aim of this
study was to investigate whether morphological changes occur in the renal
vasculature in hydronephrosis and the possible mechanisms involved. A model of
complete unilateral ureteral obstruction (CUUO) was used. Experimental animals
were divided into five groups: a normal control group (N) and groups of animals
at 1st week (O1), 2nd week (O2), 4th week (O4) and 8th week (O8) after CUUO.
Blood pressure was measured, renal arterial trees and glomeruli were assessed
quantitatively, and renovascular three-dimensional reconstruction was performed
on all groups. Glomerular ultrastructural changes were examined by transmission
electron microscopy. The results showed that the systolic blood pressure was
significantly increased in the obstructed groups (O1, O2, O4 and O8). Three
dimensional reconstruction showed sparse arterial trees in the O8 group, and a
tortuous and sometimes ruptured glomerular basement membrane was found in the O4
and O8 groups. Furthermore, epithelial media thickness and media/lumen ratio were
increased, lumen diameters were decreased, and the cross-sectional area of the
media was unaltered in the segmental renal artery, interlobar artery and afferent
arterioles, respectively. In conclusion, renal arterial trees and glomeruli were
dramatically altered following CUUO and the changes may be partially ascribed to
vascular remodeling. Elucidation of the molecular mechanisms of renovascular
morphological alterations will enable the development of potential therapeutic
approaches for hydronephrosis.
PMID- 25135732
TI - Up-regulated expression of Tim-3/Gal-9 at maternal-fetal interface in pregnant
woman with recurrent spontaneous abortion.
AB - The relationship between T cell immunoglobulin domain and mucin domain protein 3
(Tim-3)/Galectin (Gal)-9 pathway and recurrent spontaneous abortion (RSA) was
studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were
investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by
Western blotting. Meanwhile, the concentration of interleukin (IL)-4 and IL-12 in
peripheral blood plasma was determined by ELISA in 25 healthy fertile non
pregnant controls, the normal early gravidas and pregnant women with RSA
mentioned above, respectively. It was found that the relative expression levels
of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant
women with RSA as compared with those in the normal early gravidas. The
concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was
lower than that of the normal early gravidas (P<0.05) and healthy fertile non
pregnant controls (P<0.05), but that of IL-2 in pregnant women with RSA was
significantly higher than that of the normal early gravidas (P<0.05) and healthy
fertile non-pregnant controls (P<0.05). It was suggested that the overexpression
of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA.
PMID- 25135733
TI - Effects of IL-17 on expression of GRO-alpha and IL-8 in fibroblasts from nasal
polyps.
AB - Recent studies indicated that interleukin (IL)-17, growth-related oncogene (GRO)
alpha and IL-8 play an important role in the pathogenesis of nasal polyps.
However, the effects of the increased amount of IL-17 and the production of GRO
alpha and IL-8 in human nasal polyp fibroblasts are not completely understood.
This study aimed to determine the effects of the increased IL-17 on the changes
of GRO-alpha and IL-8 expression in human nasal polyp fibroblasts and further
investigate the mechanism of neutrophil infiltration in nasal polyps. Nasal polyp
fibroblasts were isolated from six cases of human nasal polyps, and the cells
were stimulated with five different concentrations of IL-17. Real-time
fluorescence quantitative polymerase chain reaction (RT-PCR) was used to detect
the mRNA expression of GRO-alpha and IL-8. The mRNA of GRO-alpha and IL-8 was
expressed in unstimulated controls and remarkably increased by stimulation with
IL-17. Moreover, the levels of GRO-alpha and IL-8 produced by fibroblasts were
increased gradually with the increases in IL-17 concentrations. The present study
showed that nasal fibroblasts can produce GRO-alpha and IL-8, and their
production is remarkably enhanced by IL-17 stimulation, thereby clarifying the
mechanism of the IL-17 mediated neutrophil infiltration in nasal polyps. These
findings might provide a rationale for using IL-17 inhibitors as a treatment for
nasal inflammatory diseases such as nasal polyps.
PMID- 25135734
TI - Analysis of Th1/Th2 response pattern for erythrodermic psoriasis.
AB - As one of the most serious types of psoriasis, pathogenesis of erythrodermic
psoriasis (EP) is unclear so far. In this study, we aimed to detect the levels of
Th1/Th2 cytokine-associated transcription factors and T-lymphocyte clone in
peripheral blood mononuclear cells (PBMCs) derived from EP patients, and gene
expression level of T-bet/GATA-3 in skin lesion. The potential role of Th1/Th2
reaction pattern played in the pathogenesis of EP was also discussed. Serum
levels of IFN-gamma, IL-2, IL-4 and IL-10 were quantified by ELISA among 16 EP
patients, 20 psoriasis vulgaris (PV) patients and 15 healthy controls. The
expression levels of T-bet/GATA-3 in the skin lesion and PBMCs were examined by
real-time qPCR. The ratio of Th1/Th2 was measured by flow cytometry. The levels
of IFN-gamma, IL-2, IL-4 and IL-10 were higher in EP patients than in the healthy
controls. The levels of IL-4 and IL-10 were 69.44+/-11.45 and 12.62+/-4.57 pg/mL,
respectively, in EP patients, significantly higher than those in PV patients and
healthy controls (P<0.05). Flow cytometry revealed the levels of both Th1 and Th2
in PBMCs from EP patients were higher than those in healthy controls, and the
Th1/Th2 ratio was dramatically lower than in PV patients (P<0.01). The ratios of
IFN-gamma/IL-4 and T-bet/GATA-3 in EP patients were both less than 1.0,
suggesting a reversal when compared with the other two groups. Our study
indicated that the EP patients exerted a Th1/Th2 bidirectional response pattern,
and the balance of Th cell subsets inclines to Th2, which might be one of the
important mechanisms of EP pathogenesis.
PMID- 25135735
TI - Mutual effect between neuropeptides and inflammatory cytokines in neurogenic
SMSCs of human temporomandibular joint.
AB - In temporomandibular disorders (TMD), pain takes place when neuropeptides
stimulate synovial tissue to produce several cytokines such as interleukin (IL)
1beta, IL-6 and tumor necrosis factor (TNF)-alpha, which activate neurons and
glia of synovial membrane at the bilaminar regions of temporomandibular joint
(TMJ). It has been reported that, after neurogenic differentiation, the synovial
mesenchymal stem cells (SMSCs), deriving from TMJ, possess the same cytological
features as the neuronal cells. This study examined the ability of substance P
(SP) and calcitonin gene-related peptide (CGRP) to stimulate SMSCs and neurogenic
SMSCs secreting inflammatory cytokines during TMD, evaluated the mutual effects
of inflammatory cytokines and neuropeptides and tested the analgesic effect of
hyaluronic acid (HA). The levels of IL-1beta, IL-6 and TNF-alpha in SMSCs and
neurogenic SMSCs in the presence of neuropeptides were measured by ELISA. SP and
CGRP produced by SMSCs and neurogenic SMSCs were determined by RT-PCR and Western
blotting. The results showed that the expression of SP and CGRP was significantly
enhanced in the neurogenic SMSCs in response to IL-1beta, IL-6 and TNF-alpha, and
the effect was remarkably inhibited by HA. IL-1beta, IL-6 and TNF-alpha, in
return, could be enhanced in the neurogenic SMSCs upon stimulation by SP and
CGRP. Neuropeptides and inflammatory cytokines might work mutually on the TMD
pain. The HA-mediated analgesic effect may be implicated in the inhibition of SP
and CGRP expression in neurogenic SMSCs.
PMID- 25135736
TI - Calcium hydroxide removal in curved root canals with apical transportation In
Vitro.
AB - Calcium hydroxide (CH) is applied to improve disinfection of root canals in most
root canal retreatment. This study aimed to analyze the CH removal efficacy using
7 different root preparing files (K file, pre-curved K file, EndoActivator,
Ultrasonic file, pre-curved ultrasonic file, F file and needle irrigation alone)
with apical transportation. Standardized models of curved canal with such apical
transportation or not were set up before applying CH to root canal for 7 days.
Seven techniques described above were used for its removal. Then the roots were
disassembled and digital photos were taken. The ratio of residual CH in the
overall canal surface was calculated using the image analyzer image pro plus 6.0.
The data were analyzed using one-way ANOVA with post hoc Tukey test. Results
revealed that CH was effectively removed (P<0.05) by using all 6 mechanical
methods except irrigation alone. In curved root canals with apical
transportation, EndoActivator, pre-curved ultrasonic file and F file were found
to be more effective in removing CH than the other four file (P<0.001), while
there was no significant difference among EndoActivator, pre-curved ultrasonic
file and F file groups (P>0.05). The percentage of residual CH in the canal with
apical transportation was higher than that in the canal without apical
transportation (P<0.05). In conclusion, CH can be hardly removed completely.
Canal with apical transportation will result in insufficient CH removal.
EndoActivator, pre-curved ultrasonic file and F file are more effective in the
curved root canal with apical transportation.
PMID- 25135737
TI - Safety and efficacy of endoscopic retrograde cholangiopancreatography for common
bile duct stones in liver cirrhotic patients.
AB - In order to investigate the safety and efficacy of endoscopic retrograde
cholangiopancreatograpy (ERCP) in liver cirrhosis patients with common bile duct
stones, we retrospectively analyzed data of 46 common bile duct stones patients
with liver cirrhosis who underwent ERCP between 2000 and 2008. There were 12
cases of Child-Pugh A, 26 cases of Child-Pugh B, and 8 cases of Child-Pugh C. 100
common bile duct stones patients without liver cirrhosis were randomly selected.
All the patients were subjected to ERCP for biliary stones extraction. The rates
of bile duct clearance and complications were compared between cirrhotic and non
cirrhotic patients. The success rate of selective biliary cannulation was 95.6%
in liver cirrhotic patients versus 97% in non-cirrhotic patients (P>0.05). The
bile duct clearance rate was 87% in cirrhotic patients versus 96% in non
cirrhotic patients, but the difference was not statistically significant. Two
liver cirrhotic patients (4.35%, 2/46) who were scored Child-Pugh C had
hematemesis and melena 24 h after ERCP. The hemorrhage rate after ERCP in non
cirrhotic patients was 3%. The hemorrhage rate associated with ERCP in Child-Pugh
C patients was significantly higher (25%, 2/8) than that (3%, 3/100) in non
cirrhotic patients (P<0.01%). There was no significant difference between these
two groups in the rate of post-ERCP pancreatitis (PEP) and cholangitis. ERCP is
safe and effective for Child-Pugh A and B cirrhotic patients with common bile
duct stones. Hemorrhage risk in ERCP is higher in Child-Pugh C patients.
PMID- 25135738
TI - Correlation between low tube voltage in dual source CT coronary artery imaging
with image quality and radiation dose.
AB - The influence of low tube voltage in dual source CT (DSCT) coronary artery
imaging on image quality and radiation dose and its application value in clinical
practice were investigated. Totally, 300 cases of chest pain with low body mass
index (BMI <18.5 kg/m(2)) subjected to DSCT coronary artery imaging were
prospectively enrolled. The heart rate in all patients were greater than 65/min.
The retrospective ECG gated scanning mode and simple random sampling method were
used to assign the patients into groups A, B and C (n=100 each). The patients in
groups A, B and C experienced 120-, 100-, and 80-kV tube voltage imaging
respectively, and the image quality was evaluated. The CT volume dose index
(CTDIvol) and dose length product (DLP) were recorded, and the effective dose
(ED) was calculated in each group. The image quality scores and radiation doses
in groups were compared, and the influence of tube voltage on image quality and
radiation dose was analyzed. The results showed that the excellent rate of image
quality in groups A, B and C was 95.69%, 94.72% and 96.33% respectively with the
difference being not statistically significant among the three groups (P>0.05).
The CTDIvol values in groups A, B and C were 51.35+/-12.21, 21.28+/-7.13 and
6.34+/-3.34 mGy, respectively, with the difference being statistically
significant (P<0.05). The ED values in groups A, B and C were 9.27+/-1.63, 4.56+/
2.29 and 2.29+/-1.69 mSv, respectively, with the difference being statistically
significant (P<0.05). It was suggested that for the patients with low BMI, the
application of DSCT coronary artery imaging with low tube voltage can obtain
satisfactory image quality, and simultaneously, significantly reduce the
radiation dose.
PMID- 25135739
TI - Electronically transparent graphene replicas of diatoms: a new technique for the
investigation of frustule morphology.
AB - The morphogenesis of the silica cell walls (called frustules) of unicellular
algae known as diatoms is one of the most intriguing mysteries of the diatoms. To
study frustule morphogenesis, optical, electron and atomic force microscopy has
been extensively used to reveal the frustule morphology. However, since silica
frustules are opaque, past observations were limited to outer and fracture
surfaces, restricting observations of interior structures. Here we show that
opaque silica frustules can be converted into electronically transparent graphene
replicas, fabricated using chemical vapor deposition of methane. Chemical vapor
deposition creates a continuous graphene coating preserving the frustule's shape
and fine, complicated internal features. Subsequent dissolution of the silica
with hydrofluoric acid yields a free-standing replica of the internal and
external native frustule morphologies. Electron microscopy renders these graphene
replicas highly transparent, revealing previously unobserved, complex, three
dimensional, interior frustule structures, which lend new insights into the
investigation of frustule morphogenesis.
PMID- 25135740
TI - LDH is an adverse prognostic factor independent of ISS in transplant-eligible
myeloma patients receiving bortezomib-based induction regimens.
AB - BACKGROUND: Serum lactate dehydrogenase (LDH) has been an adverse prognostic
factor for myeloma but does not feature in the International Staging System
(ISS). We examined whether elevated serum LDH at diagnosis remains an adverse
risk factor independent of ISS for survivals transplant-eligible myeloma patients
receiving early/frontline bortezomib-based induction, followed by autologous stem
cell transplantation (ASCT). PATIENTS: Seventy-seven transplant-eligible Chinese
patients received three induction regimens [staged approach (N = 25), PAD (N =
19), VTD (N = 33)], followed by ASCT and thalidomide maintenance. RESULTS: Five
year overall (OS) and event-free (EFS) survivals were 66.4% and 36.2%. There was
no difference in demographics, complete remission/near complete remission (CR/nCR
rates postinduction or ASCT, and survivals among patients induced by the three
induction regimens. Elevated LDH was associated with male gender (P = 0.006), ISS
III (P = 0.042) and serum beta2-microglobulin (P = 0.040). Univariate analysis
showed that elevated LDH, ISS III, high beta2-microglobulin, and failure to
attain CR/nCR post-ACST were risk factors adversely impacting both OS and EFS.
Multivariate analysis showed that elevated LDH was the only factor impacting both
OS (P = 0.007) and EFS (P = 0.008). CONCLUSION: In this uniformly treated cohort
of transplant-eligible myeloma patients, elevated serum LDH is an adverse risk
factor independent of ISS for both OS and EFS. Bortezomib-based induction/ASCT
regimen had not abolished the adverse impact of elevated LDH.
PMID- 25135741
TI - Silica exposure and altered regulation of autoimmunity.
AB - Silica particles and asbestos fibers, which are known as typical causatives of
pneumoconiosis, induce lung fibrosis. Moreover, silicosis patients often
complicate with autoimmune diseases, and asbestos-exposed patients suffer from
malignant diseases such as pleural mesothelioma and lung cancer. We have been
conducting experimental studies to investigate altered regulation of self
tolerance caused by silica exposure, including analyses using specimens such as
plasma and immunocompetent cells obtained from silicosis patients, as a means of
examining the supposition that silica exposure induces molecular and cellular
biological alterations of immune cells. These approaches have resulted in the
detection of several specific autoantibodies, alterations of CD95/Fas and its
related molecules, and evidence of chronic activation of responder T cells and
regulatory T cells following silica exposure. In this review, we present details
of our investigations as an introduction to scientific approaches examining the
immunological effects of environmental and occupational substances.
PMID- 25135742
TI - Reduced dynamic hyperinflation after LVRS is associated with improved exercise
tolerance.
AB - INTRODUCTION: Dynamic hyperinflation (DH) after lung volume reduction surgery
(LVRS) has not been well studied. It is not known if reductions in DH correlate
with improvements in exercise performance post-LVRS. METHODS: Forty-two upper
lobe predominant emphysema patients who underwent LVRS were analyzed. Inspiratory
capacity was measured every 2 min during symptom-limited cardiopulmonary exercise
test (CPET) and end-expiratory lung volumes (EELV) were calculated. The main
measure of DH was EELV/TLC ratio matched at metabolic isotimes (based on the post
rehabilitation VCO2max). RESULTS: Patients had very severe airflow obstruction
(FEV1 28.3 +/- 7.0% predicted), were hyperinflated (TLC 125 +/- 17% predicted)
and gas trapped (RV 198 +/- 39% predicted). Compared to the post-rehab baseline,
dynamic hyperinflation (EELV/TLC) was significantly reduced after LVRS at 6, 12,
24, and 36 months. There were also increases in inspiratory reserve volume at
matched isotimes after surgery. Patients adopted a slower, deeper breathing
pattern during exercise after LVRS, which strongly correlated to reductions in
DH. There were significant correlations between reductions in DH (EELV/TLC @50%
VCO2max) and improvements in 6 min walk distance (Pearson r = -0.411, p = 0.02, n
= 33) and maximal watts on CPET (Spearman r = -0.536, p = 0.001, n = 33) when
comparing post-rehabilitation and 6 month post-LVRS values. CONCLUSION: Dynamic
hyperinflation during exercise was reduced after LVRS (up to 3 years) and there
was a strong association between alterations in breathing pattern and reduced DH
after LVRS. This is the first study to demonstrate that reductions in DH
correlated with improved exercise performance following LVRS.
PMID- 25135743
TI - Pooled safety analysis of the fixed-dose combination of indacaterol and
glycopyrronium (QVA149), its monocomponents, and tiotropium versus placebo in
COPD patients.
AB - BACKGROUND: To further assess the safety profile of the fixed-dose combination of
indacaterol and glycopyrronium (QVA149) and its monocomponents; we investigated
the impact of individual patient-level factors and time by integrating the
patient-level safety data from the QVA149 clinical programme with relevant
information from the independent indacaterol and glycopyrronium safety databases.
METHODS: Data from 11,404 patients with chronic obstructive pulmonary disease
(COPD) were pooled from 14 clinical studies of QVA149, indacaterol and
glycopyrronium of >=3 month's duration with at least two of the treatment groups:
QVA149 110/50 MUg, glycopyrronium 50 MUg, indacaterol 150 MUg, placebo or
tiotropium 18 MUg. Overall hazard ratio (HR) was assessed between the active
treatments and placebo and in various subgroups related to severity of airways
obstruction, inhaled corticosteroid use, cardiovascular risk factors, sex, age
and body mass index for death, serious cases of cardio- and cerebrovascular (CCV)
events, major adverse cardiovascular events (MACEs), pneumonia, COPD
exacerbations requiring hospitalisation or atrial flutter/fibrillation (AF/F).
RESULTS: The HR for QVA149 versus placebo showed no significant increase in the
overall risk for death (HR [95% confidence interval]: 0.93 [0.34-2.54]); CCV
events (0.60 [0.29-1.24]); MACE (1.04 [0.45-2.42]); pneumonia (1.10 [0.54-2.25]);
COPD exacerbations (0.60 [0.40-0.91]); and AF/F (1.03 [0.49-2.18]). Similar
results were observed for indacaterol, glycopyrronium and tiotropium versus
placebo for overall risk and in analysed subgroups. CONCLUSIONS: There was no
increase in the risk for the investigated safety endpoints for the fixed-dose
combination QVA149, and it had a comparable safety profile as its monocomponents
and tiotropium versus placebo.
PMID- 25135744
TI - SQ HDM SLIT-tablet (ALK) in treatment of asthma--post hoc results from a
randomised trial.
AB - INTRODUCTION: In a double-blind, placebo-controlled trial (EudraCT identifier:
2006-001795-20), the standardised quality (SQ) house dust mite (HDM) sublingual
immunotherapy (SLIT)-tablet (ALK, Denmark) was investigated. METHOD: The trial
included 604 subjects, >=14 years, with mild-moderate HDM allergic asthma.
Subjects were randomised 1:1:1:1 to 1, 3 or 6 SQ-HDM or placebo once daily. The
primary endpoint was reduction in inhaled corticosteroid (ICS) after one year.
ICS reduction, asthma quality of life questionnaire (AQLQ) and asthma control
questionnaire (ACQ) score was analysed post hoc in a subgroup with daily ICS use
of 400-800 MUg and ACQ score of 1-1.5, corresponding to partly controlled asthma
(N = 108). RESULTS: The trial met its primary endpoint. In the subgroup, the
difference between placebo and 6 SQ-HDM in change from baseline in daily ICS use
was 327 MUg (p < 0.0001), while it was 0.52 (p = 0.010) for AQLQ. The treatment
effect on ICS reduction and AQLQ was increased for the subgroup versus the
residual population (ICS reduction: p < 0.001); AQLQ: p = 0.044). CONCLUSION: In
this subgroup, including only patients with partly controlled asthma, the benefit
of 1 year of treatment with SQ HDM SLIT-tablet was significantly higher than for
the less severe full population, both in terms of increased asthma control and
improved quality of life.
PMID- 25135745
TI - Persistent systemic inflammation and symptoms of depression among patients with
COPD in the ECLIPSE cohort.
AB - BACKGROUND: Depression is highly prevalent among patients with Chronic
Obstructive Pulmonary Disease (COPD). The relationship of depression with
systemic inflammation in COPD remains unknown. The objective of this
observational study was to compare depression scores at baseline and after 36
months follow-up between COPD patients with persistent systemic inflammation
(PSI) and never inflamed patients (NI) in the ECLIPSE cohort. METHODS: The
ECLIPSE study included 2164 COPD patients. Parameters assessed at baseline and at
36 months follow-up included: demographics, clinical characteristics and symptoms
of depression (Center for Epidemiologic Studies of Depression, CES-D). Patients
classified as NI had zero and patients with PSI had >=2 inflammatory biomarkers
(white blood cell count, hsCRP, IL-6, and fibrinogen) in the upper quartile, at
baseline and 12 months later. FINDINGS: 350 patients (29.1%) were NI and 131
patients (10.9%) had PSI. At baseline, mean CES-D score was higher in patients
with PSI than in NI patients (11.7 (8.6) vs. 9.2 (8.9) points, p = 0.01).
Differences were not confirmed after adjustment for possible confounders (beta
(95% CI) = 0.02 (-3.87 to 15.29), adjusted p = 0.98). At 36 months follow-up, CES
D scores were comparable in PSI and NI patients (12.2 (9.3) vs. 10.5 (9.0)
points, p = 0.08) as were their temporal changes (0.5 (8.3) vs. 1.3 (7.9) points,
p = 0.30). CONCLUSION: The ECLIPSE study does not support a strong relationship
between PSI and symptoms of depression at baseline and after 36 months follow-up
in COPD. FUNDING: The study was sponsored by GlaxoSmithKline.
PMID- 25135746
TI - Evaluation of epicardial fat tissue thickness in patients with hyperthyroidism.
AB - BACKGROUND: Thyroid hormones have several effects on the cardiovascular system,
and recent studies have found that thyroid disorders affect coronary intima-media
thickness (CIMT) in particular. Despite increased CIMT in patients with
hyperthyroidism, the extent of the relationship between CIMT and epicardial fat
thickness (EFT) in those patients is unknown. Furthermore, there is no report
evaluating the relationship between EFT and overt hyperthyroidism (OH) in the
literature. In this study, we aim to evaluate the effectiveness of EFT in
predicting atherosclerosis as well as CIMT in patients with OH. METHODS: A total
of 30 newly diagnosed, untreated overt hyperthyroid patients and 44 control
subjects were included in the study. EFT was measured using a commercially
available echocardiography machine (VIVID 7; General Electric Medical Systems,
Norway) with a 2.5-MHz probe. The echo-free space between the visceral and
parietal pericardium on the anterior wall of the right ventricle was diagnosed as
EFT. A linear-array imaging probe of the same echocardiography probe was used to
evaluate the CIMT of the right common carotid artery. RESULTS: The hyperthyroid
patients had a significantly greater EFT (mean: 4.31 +/- 1.12 mm) than the
healthy subjects (mean: 3.11 +/- 0.84 mm; p < 0.001). CIMT was also significantly
greater in the hyperthyroid patients (mean: 0.62 +/- 0.17 mm) than in the healthy
subjects (mean: 0.50 +/- 0.11 mm; p < 0.01). CONCLUSION: In conclusion, the
present study shows that mean EFT and CIMT were significantly higher in OH
patients, irrespective of confounding factors such as hypertension.
PMID- 25135747
TI - Differentiation of DctA and DcuS function in the DctA/DcuS sensor complex of
Escherichia coli: function of DctA as an activity switch and of DcuS as the C4
dicarboxylate sensor.
AB - The C4-dicarboxylate responsiveness of the sensor kinase DcuS is only provided in
concert with C4-dicarboxylate transporters DctA or DcuB. The individual roles of
DctA and DcuS for the function of the DctA/DcuS sensor complex were analysed. (i)
Variant DctA(S380D) in the C4-dicarboxylate site of DctA conferred C4
dicarboxylate sensitivity to DcuS in the DctA/DcuS complex, but was deficient for
transport and for growth on C4-dicarboxylates. Consequently transport activity of
DctA is not required for its function in the sensor complex. (ii) Effectors like
fumarate induced expression of DctA/DcuS-dependent reporter genes (dcuB-lacZ) and
served as substrates of DctA, whereas citrate served only as an inducer of dcuB
lacZ without affecting DctA function. (iii) Induction of dcuB-lacZ by fumarate
required 33-fold higher concentrations than for transport by DctA (Km = 30 MUM),
demonstrating the existence of different fumarate sites for both processes. (iv)
In titration experiments with increasing dctA expression levels, the effect of
DctA on the C4-dicarboxylate sensitivity of DcuS was concentration dependent. The
data uniformly show that C4-dicarboxylate sensing by DctA/DcuS resides in DcuS,
and that DctA serves as an activity switch. Shifting of DcuS from the
constitutive ON to the C4-dicarboxylate responsive state, required presence of
DctA but not transport by DctA.
PMID- 25135748
TI - Synthesis of novel carbazole fused coumarin derivatives and DFT approach to study
their photophysical properties.
AB - Novel coumarin derivatives have been synthesized by the classical Knoevenagel
condensation of 4-hydroxy-9-methyl-9H-carbazole-3-carbaldehyde with active
methylene compounds and characterized. Effect of solvent polarity on the
photophysical properties, absorption and emission has been studied. The
photophysical properties of the synthesized coumarins have been compared with
some of the established analogous coumarin derivatives. Investigation of the
structural parameters and understanding photophysical properties of the
synthesized coumarin derivatives were carried out using Density Functional Theory
(DFT) and Time Dependant Density Functional Theory (TDDFT) computations. The
experimental values were correlated with the theoretical derived results. The
ratio of the excited state and the ground state dipole moments was calculated by
using solvatochromic and solvatofluoric data and compared with the values
obtained from DFT and TDDFT computations.
PMID- 25135749
TI - Regarding the tongue protrusion as an indicator of vital burning. Much ado about
nothing.
PMID- 25135750
TI - Molecular analysis of different classes of RNA molecules from formalin-fixed
paraffin-embedded autoptic tissues: a pilot study.
AB - For a long time, it has been thought that fresh and frozen tissues are the only
possible source of biological material useful to extract nucleic acids suitable
for downstream molecular analysis. Recently, for forensic purpose such as
personal identification, also fixed tissues have been used to recover DNA
molecules, whereas RNA extracted from such material is still considered too
degraded for gene expression studies. In the present pilot study, we evaluated
the possibility to use forensic formalin-fixed paraffin-embedded (FFPE) samples,
collected at autopsy at different postmortem intervals (PMI) from four
individuals, to perform advanced molecular analyses. In particular, we performed
qualitative and quantitative analyses of total RNAs extracted from different FFPE
tissues and put expression profiles in relation with the organ type and the
duration of PMI. Different classes of RNA molecular targets were studied by real
time quantitative RT-PCR. We report molecular evidence that small RNAs are the
only RNA molecules still detectable in all the FFPE autoptic tissues. In
particular, microRNAs (miRNAs) represent a consistent, stable, and well-preserved
molecular target detectable even from tissue sources displaying signs of ongoing
putrefaction at autopsy. In this pilot study, we show that miRNAs could represent
a highly sensitive and potentially useful forensic marker. Amplification of
specific miRNAs using paraffin-embedded blocks could facilitate retrospective
molecular analysis using specific forensic-archived tissues chosen as most
suitable according to PMI, and this approach would address molecular evidence in
forensic cases in which fresh or frozen material is no longer available.
PMID- 25135751
TI - Projection radiography of the clavicle: still recommendable for forensic age
diagnostics in living individuals?
AB - As superimposition effects often impede the evaluation of the ossification status
of the medial clavicular epiphysis in standard posterior-anterior (PA)
radiographs, additional oblique images (right anterior oblique, RAO, and left
anterior oblique, LAO) are currently recommended to allow for reliable stage
assessments. The present study examines the influence of the radiographic
projection type on stage determination. To this end, 836 sternoclavicular joints
were prospectively obtained during forensic autopsies of bodies aged between 15
and 30 years. Subsequently, three different radiographs (PA, RAO, and LAO) were
taken from each specimen and separately evaluated as to the developmental stage
of the medial clavicular epiphysis. A forensically established five-stage
classification system was used. In 25 % of the cases, the medial clavicular
epiphysis depicted in an oblique projection showed a different ossification stage
than in the PA projection. In at least 10 % of the cases, a higher ossification
stage was observed which would have significant disadvantages in criminal
proceedings (ethically unacceptable error). In conclusion, the usage of the
current radiographic reference data, which rely upon chest radiographs taken as
PA projections, appears to be inadmissible for oblique projections. Projection
radiography of the clavicle can therefore no longer be recommended for forensic
age estimation practice. As to the question of whether an individual has achieved
the age of 18 or 21, computed tomography of the clavicle must be regarded as the
exclusive method of choice.
PMID- 25135752
TI - CD30 expression in de novo diffuse large B-cell lymphoma: a population-based
study from British Columbia.
AB - Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with variable
therapeutic responses and alternative therapies are needed for patients with
unfavourable treatment outcomes after standard treatment with R-CHOP (rituximab,
cyclophosphamide, doxorubicin, vincristine, prednisone). One promising candidate
is brentuximab vedotin, an antibody-drug conjugate targeting CD30-expressing
cells. However, CD30 (TNFRSF8) expression patterns in DLBCL are not well
described thus far. Here, we examined CD30 expression in a population-based
cohort of immunocompetent patients from British Columbia with de novo DLBCL using
immunohistochemistry. 385 cases of formalin-fixed paraffin-embedded DLBCL in
tissue microarrays were evaluated. 95 cases (25%) harboured CD30+ tumour cells.
Using a > 0% cut-off, CD30 expression was predictive of superior 5-year
progression-free survival within R-CHOP treated germinal centre B-cell-like (GCB)
DLBCL (86% vs. 64%, P = 0.020), which was independent of the International
Prognostic Index. Epstein-Barr virus (EBV) was identified in 11 (3%) cases, all
of which were non-GCB (P = 0.001) and almost exclusively positive for CD30
expression (10/11) (P < 0.001). We conclude CD30 is expressed in a substantial
proportion of DLBCL and CD30 immunohistochemistry may be a useful prognostic
marker in R-CHOP treated GCB-DLBCL. The significant association of CD30 with EBV
positive non-GCB DLBCL suggests a distinct pathobiology for these cases.
PMID- 25135753
TI - Purifying selection against gene conversions between the polyamine transport
(TPO) genes of Saccharomyces species.
AB - Saccharomyces species have five TPO genes, TPO1 through TPO5, coding for proteins
that are involved in up taking or excreting intracellular spermine, putrescine or
spermidine. Here, we investigate the evolutionary fate and functional impacts of
gene conversions between these genes. Our results show that gene conversions
occurred only between the TPO2 and TPO3 genes of the six Saccharomyces species we
studied. They also show that these gene conversions occurred independently in all
six species. The facts that they only occur between closely related genes having
similar function, and that they are limited to the transmembrane domain of these
proteins, suggest that they have little functional impact. These gene conversions
therefore likely represent neutral mutations which are not subject to purifying
selection.
PMID- 25135755
TI - Spin-orbit effects in square-planar Pt(II) complexes with bidentate and
terdentate ligands: theoretical absorption/emission spectroscopy.
AB - The absorption and emission properties of five Pt(ii) planar complexes with
bidentate ligands, namely [Pt(bpy)Cl2] (bpy = 2,2'-bipyridine) and [Pt(ppy)Cl2](
) (ppy = 2-phenylpyridine) , and terdentate ligands, namely [Pt(tpy)Cl](+) (tpy =
2,2':6',2''-terpyridine) , [Pt(phbpyR)Cl] (phbpy = 6-phenyl-2,2'-bipyridine; R =
H) and [Pt(dpybR)Cl] (dpyb = 2,6-di(2-pyridyl)benzene; R = CH3) were investigated
by means of density functional theory (DFT) and time-dependent DFT (TD-DFT)
methods including solvent correction and spin-orbit coupling (SOC). The DFT
optimized structures of the five complexes in the electronic ground state are in
agreement with the experimental X-ray data and the theoretical absorption spectra
reproduce quantitatively the main features of the experimental spectra. It is
shown that the structures remain nearly planar in the low-lying singlet and
triplet excited states of charge transfer character, metal-to-ligand (MLCT) or
halide (Cl) to ligand (XLCT) whereas a significant distortion corresponding to
the out-of-plane-bending of the Pt-Cl bond characterizes the geometry of the
metal-centered (MC) states. In cyclometalated complexes , and this distortion is
energetically unfavorable and not competitive with radiative decay via the low
lying MLCT and XLCT excited states. The absorption spectra of all complexes are
significantly affected by spin-orbit coupling (red-shift and broadening),
especially in the non-cyclometalated complexes and characterized by the presence
of pure low-lying (3)MC states. The SOC effects are less important in the
terpyridine complex the lowest part of its spectrum being contaminated by mixed
(3)MLCT/(3)XLCT states. In the cyclometalated complexes and the presence of
several LC states in the lowest part of the spectra is responsible for a small
shift to the red as compared to the other complexes. The solvatochromism that
characterizes the absorption of this class of molecules in the visible region is
interpreted by the MLCT/XLCT mixed character of the excited states in this energy
domain (400-450 nm). Indeed the solvent dependent XLCT contribution will control
the magnitude of SOC in these excited states and will move the band to the red
region when diminishing and to the blue region when increasing. As far as
emission is concerned it is shown that strongly distorted non-radiative MC
state's minima, situated below the charge transfer state's minima (DeltaE = -0.3
eV to -0.8 eV) are easily accessible upon irradiation in the visible region in
complexes and , and in to a lesser extent, leading to no or low luminescence at
room temperature. In contrast, the minima of the emissive states of mixed
MLCT/XLCT/LC character are efficiently populated in and . The luminescence of
complex , cyclometalated in the axial position, is particularly efficient because
the minimum of the lowest emissive state is well separated from those of the MC
states (DeltaE = +0.23 eV) in contrast to its analog, complex , cyclometalated in
the lateral position where the emissive MLCT/LC state minimum is nearly
degenerate with the lowest MC state minimum (DeltaE = +0.01 eV).
PMID- 25135754
TI - Clinical utility and diagnostic accuracy of faecal calprotectin for IBD at first
presentation to gastroenterology services in adults aged 16-50 years.
AB - BACKGROUND: Distinguishing inflammatory bowel disease (IBD) from functional
gastrointestinal (GI) disease remains an important issue for gastroenterologists
and primary care physicians, and may be difficult on the basis of symptoms alone.
Faecal calprotectin (FC) is a surrogate marker for intestinal inflammation but
not cancer. AIM: This large retrospective study aimed to determine the most
effective use of FC in patients aged 16-50 presenting with GI symptoms. METHODS:
FC results were obtained for patients presenting to the GI clinics in Edinburgh
between 2005 and 2009 from the Edinburgh Faecal Calprotectin Registry containing
FCs from >16,000 patients. Case notes were interrogated to identify demographics,
subsequent investigations and diagnoses. RESULTS: 895 patients were included in
the main analysis, 65% female and with a median age of 33 years. 10.2% were
diagnosed with IBD, 7.3% with another GI condition associated with an abnormal GI
tract and 63.2% had functional GI disease. Median FC in these three groups were
1251, 50 and 20 MUg/g (p < 0.0001). On ROC analysis, the AUC for FC as a
predictor of IBD vs. functional disease was 0.97. Using a threshold of >= 50
MUg/g for IBD vs. functional disease yielded a sensitivity of 0.97, specificity
of 0.74, positive predictive value of 0.37 and negative predictive value of 0.99.
Combined with alarm symptoms, the sensitivity was 1.00. CONCLUSIONS:
Implementation of FC in the initial diagnostic workup of young patients with GI
symptoms, particularly those without alarm symptoms, is highly accurate in the
exclusion of IBD, and can provide reassurance to patients and physicians.
PMID- 25135756
TI - Late pulmonary complications of treating Hodgkin lymphoma: bleomycin-induced
toxicity.
AB - INTRODUCTION: Survival of Hodgkin lymphoma (HL) patients has significantly
improved in recent decades. The current first-line therapy is doxorubicin,
bleomycin, vinblastine, dacarbazine (ABVD) +/- irradiation and may cause
pulmonary toxicity. Strategies to reduce late toxicity as well as increase
survival rate are of interest. PATIENTS AND METHODS: Pulmonary function of
previously treated HL patients was collected over a 12-month period using St.
George Respiratory Questionnaire (SGRQ), chest X-ray, dynamic inhalation lung
scintigraphy and spirometry. RESULTS: A total of 137 patients' data were
reviewed. Median time elapsed since diagnosis was 11 years (range was 2 - 30
years). Chest irradiation did not significantly worsen pulmonary function. Number
of ABVD cycles with consequential bleomycin dose showed significant correlation
with SGRQ total score in patients receiving ABVD plus chest irradiation (p =
0.01). Scintigraphy results correlated with bleomycin dose in patients receiving
ABVD without chest irradiation (right side: p = 0.099, left side: p = 0.051).
DISCUSSION: An additive negative effect of chest irradiation was not confirmed as
reflected in the literature; however, increasing cumulative bleomycin dose
worsened pulmonary function.
PMID- 25135757
TI - A neighboring group participation strategy: direct and highly diastereoselective
synthesis of 2-substituted and 2,2-bisubstituted perhydrofuro[2,3-b]pyran
derivatives.
AB - Treatment of methyl 2-C-formylmethyl-2-deoxy-beta-D-glucopyranoside (5) or methyl
2-C-acetylmethyl-2-deoxy-beta-D-glucopyranoside (1) with H2SO4-HOAc-Ac2O gave 2
acetoxyl-4,5-bis(benzyloxy)-6-[(benzyloxy)methyl]hexahydrofuro[2,3-b]pyran (6)
and acetyl 2-C-acetylmethyl-2-deoxy-alpha-D-glucopyranoside (7) respectively,
which were further reacted with nucleophiles in the presence of TMSOTf and
offered a series of 2-substituted and 2,2-disubstituted perhydrofuro[2,3-b]pyran
derivatives in high yield with excellent diastereoselectivity.
PMID- 25135758
TI - Automated hematologic analysis of bone marrow aspirate samples from healthy
Beagle dogs.
AB - BACKGROUND: Interpretation of bone marrow (BM) smears typically is comprised of
qualitative assessment and differential counting of cells. Analysis of BM fluid
with automated hematology analyzers may provide rapid characterization of cells
to supplement microscopic interpretation. OBJECTIVES: The purpose of the study
was to examine the practicality and utility of analyzing BM samples in the Advia
2120 hematology analyzer; to determine if results correlate with smear
assessment; and to establish descriptive statistics from hematologically normal
and clinically healthy Beagle dogs. METHODS: Anticoagulated BM aspirates from 3
different sites of 26 adult Beagle dogs were collected. BM samples were analyzed
in the Advia 2120, and numerical results were correlated with microscopic
assessment of corresponding BM smears. Results from automated analyses and manual
500-cell differential counts were statistically analyzed. RESULTS: Forty-six
samples were suitable for complete analysis. Results were available in
approximately 2 (Advia) and 30 (stained and cover-slipped smear) minutes. Advia
nucleated cell concentration was significantly correlated with microscopic
assessment of smear particle number and smear cellularity. Significant
correlations were also identified for Advia percent neutrophils with segmented,
band and metamylocyte neutrophils, Advia percent lymphocytes with rubricytes, and
Advia percent large unstained cells (LUC) with myeloblasts and promyelocytes.
CONCLUSIONS: Automated analysis of BM aspirates was practicable, although
techniques to obtain cellular samples and avoid clot formation could be improved.
Automated analysis may provide rapid and useful preliminary information regarding
sample cellularity, and granulocytic and erythrocytic components. Automated
analysis should not supplant microscopic assessment, but may be a useful adjunct.
PMID- 25135761
TI - Nonlinear emission of quinolizinium-based dyes with application in fluorescence
lifetime imaging.
AB - Charged molecules based on the quinolizinum cation have potential applications as
labels in fluorescence imaging in biological media under nonlinear excitation. A
systematic study of the linear and nonlinear photophysics of derivatives of the
quinolizinum cation substituted by either dimethylaniline or methoxyphenyl
electron donors is performed. The effects of donor strength, conjugation length,
and symmetry in the two-photon emission efficiency are analyzed in detail. The
best performing nonlinear fluorophore, with two-photon absorption cross sections
of 1140 GM and an emission quantum yield of 0.22, is characterized by a symmetric
D-pi-A(+)-pi-D architecture based on the methoxyphenyl substituent. Application
of this molecule as a fluorescent marker in optical microscopy of living cells
revealed that, under favorable conditions, the fluorophore can be localized in
the cytoplasmatic compartment of the cell, staining vesicular shape organelles.
At higher dye concentrations and longer staining times, the fluorophore can also
penetrate into the nucleus. The nonlinearly excited fluorescence lifetime imaging
shows that the fluorophore lifetime is sensitive to its location in the different
cell compartments. Using fluorescence lifetime microscopy, a multicolor map of
the cell is drafted with a single dye.
PMID- 25135759
TI - Temporal spying and concealing process in fibre-optic data transmission systems
through polarization bypass.
AB - Recent research has been focused on the ability to manipulate a light beam in
such a way to hide, namely to cloak, an event over a finite time or localization
in space. The main idea is to create a hole or a gap in the spatial or time
domain so as to allow for an object or data to be kept hidden for a while and
then to be restored. By enlarging the field of applications of this concept to
telecommunications, researchers have recently reported the possibility to hide
transmitted data in an optical fibre. Here we report the first experimental
demonstration of perpetual temporal spying and blinding process of optical data
in fibre-optic transmission line based on polarization bypass. We successfully
characterize the performance of our system by alternatively copying and then
concealing 100% of a 10-Gb s(-1) transmitted signal.
PMID- 25135760
TI - Smoking induces overexpression of immediate early genes in active Graves'
ophthalmopathy.
AB - BACKGROUND: Cigarette smoking is a risk factor for the development of Graves'
ophthalmopathy (GO). In a previous study of gene expression in intraorbital fat,
adipocyte-related immediate early genes (IEGs) were overexpressed in patients
with GO compared to controls. We investigated whether IEGs are upregulated by
smoking, and examined other pathways that may be affected by smoking. METHODS:
Gene expression in intraorbital fat was studied in smokers (n=8) and nonsmokers
(n=8) with severe active GO, as well as in subcutaneous fat in thyroid-healthy
smokers (n=5) and nonsmokers (n=5) using microarray and real-time polymerase
chain reaction (PCR). RESULTS: With microarray, eight IEGs were upregulated more
than 1.5-fold in smokers compared to nonsmokers with GO. Five were chosen for
confirmation and were also overexpressed with real-time PCR. Interleukin-1
beta/IL-1B/(2.3-fold) and interleukin-6/IL-6/(2.4-fold) were upregulated both
with microarray and with real-time PCR in smokers with GO compared to nonsmokers.
Major histocompatibility complex, class II, DR beta 1/HLA-DRB1/was upregulated
with microarray (2.1-fold) and with borderline significance with real-time PCR.
None of these genes were upregulated in smokers compared to nonsmokers in
subcutaneous fat. CONCLUSIONS: IEGs, IL-1B, and IL-6 were overexpressed in
smokers with severe active GO compared to nonsmokers, suggesting that smoking
activates pathways associated with adipogenesis and inflammation. This study
underlines the importance of IEGs in the pathogenesis of GO, and provides
evidence for possible novel therapeutic interventions in GO. The mechanisms
activated by smoking may be shared with other conditions such as rheumatoid
arthritis.
PMID- 25135762
TI - Complement mutations in diacylglycerol kinase-epsilon-associated atypical
hemolytic uremic syndrome.
AB - BACKGROUND AND OBJECTIVES: Atypical hemolytic uremic syndrome is characterized by
vascular endothelial damage caused by complement dysregulation. Consistently,
complement inhibition therapies are highly effective in most patients with
atypical hemolytic uremic syndrome. Recently, it was shown that a significant
percentage of patients with early-onset atypical hemolytic uremic syndrome carry
mutations in diacylglycerol kinase-epsilon, an intracellular protein with no
obvious role in complement. These data support an alternative, complement
independent mechanism leading to thrombotic microangiopathy that has implications
for treatment of early-onset atypical hemolytic uremic syndrome. To get
additional insights into this new form of atypical hemolytic uremic syndrome, the
diacylglycerol kinase-epsilon gene in a cohort with atypical hemolytic uremic
syndrome was analyzed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Eighty
three patients with early-onset atypical hemolytic uremic syndrome (<2 years)
enrolled in the Spanish atypical hemolytic uremic syndrome registry between 1999
and 2013 were screened for mutations in diacylglycerol kinase-epsilon. These
patients were also fully characterized for mutations in the genes encoding factor
H, membrane cofactor protein, factor I, C3, factor B, and thrombomodulin CFHRs
copy number variations and rearrangements, and antifactor H antibodies. RESULTS:
Four patients carried mutations in diacylglycerol kinase-epsilon, one
p.H536Qfs*16 homozygote and three compound heterozygotes (p.W322*/p.P498R, two
patients; p.Q248H/p.G484Gfs*10, one patient). Three patients also carried
heterozygous mutations in thrombomodulin or C3. Extensive plasma infusions
controlled atypical hemolytic uremic syndrome recurrences and prevented renal
failure in the two patients with diacylglycerol kinase-epsilon and thrombomodulin
mutations. A positive response to plasma infusions and complement inhibition
treatment was also observed in the patient with concurrent diacylglycerol kinase
epsilon and C3 mutations. CONCLUSIONS: Data suggest that complement dysregulation
influences the onset and disease severity in carriers of diacylglycerol kinase
epsilon mutations and that treatments on the basis of plasma infusions and
complement inhibition are potentially useful in patients with combined
diacylglycerol kinase-epsilon and complement mutations. A comprehensive
understanding of the genetic component predisposing to atypical hemolytic uremic
syndrome is, therefore, critical to guide an effective treatment.
PMID- 25135763
TI - Factors influencing treatment of atypical hemolytic uremic syndrome.
PMID- 25135764
TI - Implementation of a CKD checklist for primary care providers.
AB - BACKGROUND AND OBJECTIVES: CKD is associated with significant morbidity,
mortality, and financial burden. Practice guidelines outlining CKD management
exist, but there is limited application of these guidelines. Interventions to
improve CKD guideline adherence have been limited. This study evaluated a new CKD
checklist (a tool outlining management guidelines for CKD) to determine whether
implementation in an academic primary care clinic improved adherence to
guidelines. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: During a 1-year period
(August 2012-August 2013), a prospective study was conducted among 13 primary
care providers (PCPs), four of whom were assigned to use a CKD checklist
incorporated into the electronic medical record during visits with patients with
CKD stages 1-4. All providers received education regarding CKD guidelines. The
intervention and control groups consisted of 105 and 263 patients, respectively.
Adherence to CKD management guidelines was measured. RESULTS: A random-effects
logistic regression analysis was performed to account for intra-group correlation
by PCP assignment and adjusted for age and CKD stage. CKD care improved among
patients whose PCPs were assigned to the checklist intervention compared with
controls. Patients in the CKD checklist group were more likely than controls to
have appropriate annual laboratory testing for albuminuria (odds ratio [OR], 7.9;
95% confidence interval [95% CI], 3.6 to 17.2), phosphate (OR, 3.5; 95% CI, 1.5
to 8.3), and parathyroid hormone (OR, 8.1; 95% CI, 4.8 to 13.7) (P<0.001 in all
cases). Patients in the CKD checklist group had higher rates of achieving a
hemoglobin A1c target<7% (OR, 2.7; 95% CI, 1.4 to 5.1), use of an angiotensin
converting enzyme inhibitor or angiotensin-receptor blocker (OR, 2.1; 95% CI, 1.0
to 4.2), documentation of avoidance of nonsteroidal anti-inflammatory drugs (OR,
41.7; 95% CI, 17.8 to 100.0), and vaccination for annual influenza (OR, 2.1; 95%
CI, 1.1 to 4.0) and pneumococcus (OR, 4.7; 95% CI, 2.6 to 8.6) (P<0.001 in all
cases). CONCLUSIONS: Implementation of a CKD checklist significantly improved
adherence to CKD management guidelines and delivery of CKD care.
PMID- 25135765
TI - Checklists as computer decision support at the point of care: a step forward in
the recognition and treatment of CKD by primary care physicians.
PMID- 25135767
TI - Commentary: Getting fathers into parenting programmes--a reflection on Panter
Brick et al. (2014).
AB - Research, policy and clinical practice focussed on engaging and working with
fathers and their children often seems to oscillate between extremes. Where
policy documents relating to children's health and wellbeing do include fathers
it is often in a restricted way, and similarly discussions about the role of
fathers in the media are often one-dimensional. It is sometimes hard to escape a
feeling of despondency at the continuing exchanges, too often made ignoring or
misinterpreting years of research regarding the importance of co-parenting and
the involvement of fathers and other carers. One of the great contributions of
child and adolescent mental health professionals has been the drawing of
attention to the importance of family processes and systemic thinking, yet in
relation to parenting, this seems to have been increasingly overlooked in recent
years with an increased focus on attachment or social learning inspired
approaches for a single parent-child dyad. In this issue of the JCPP, in a
thorough and timely review, Catherine Panter-Brick and colleagues call for a
clear change to the way parenting programmes are considered, studied and
implemented. In this commentary, we reflect on this call and look at three
challenges for CAMHS professionals.
PMID- 25135766
TI - Short-term safety and efficacy of calcium montmorillonite clay (UPSN) in
children.
AB - Recently, an association between childhood growth stunting and aflatoxin (AF)
exposure has been identified. In Ghana, homemade nutritional supplements often
consist of AF-prone commodities. In this study, children were enrolled in a
clinical intervention trial to determine the safety and efficacy of Uniform
Particle Size NovaSil (UPSN), a refined calcium montmorillonite known to be safe
in adults. Participants ingested 0.75 or 1.5 g UPSN or 1.5 g calcium carbonate
placebo per day for 14 days. Hematological and serum biochemistry parameters in
the UPSN groups were not significantly different from the placebo-controlled
group. Importantly, there were no adverse events attributable to UPSN treatment.
A significant reduction in urinary metabolite (AFM1) was observed in the high
dose group compared with placebo. Results indicate that UPSN is safe for children
at doses up to 1.5 g/day for a period of 2 weeks and can reduce exposure to AFs,
resulting in increased quality and efficacy of contaminated foods.
PMID- 25135768
TI - Patients' preferences: a discrete-choice experiment for treatment of non-small
cell lung cancer.
AB - OBJECTIVE: Lung cancer is a major cause of cancer-related deaths and thus
represents a global health problem. According to World Health Organization (WHO)
estimates, approximately 1.37 million people die each year from lung cancer.
Different therapeutic approaches as well as several treatment options exist. To
date decisions on which therapies to use have largely been made by clinical
experts. Comparative preference studies show that underlying weighting of
treatment goals by experts is not necessarily congruent with the preferences of
affected patients. AIM AND METHODS: The aim of this empirical study was to
ascertain patient preferences in relation to treatment of non-small-cell lung
cancer (NSCLC). After identification of patient-relevant treatment attributes via
literature review and qualitative interviews(ten) a discrete-choice experiment
including seven patient-relevant attributes was conducted using a fractional
factorial NGene-design. Statistical data analysis was performed using latent
class models. RESULTS: The qualitative part of this study identified outcome
measures related to efficacy, side effects and mode of administration. A total of
211 NSCLC patients (N = 211) participated in the computer-assisted personal
interview. A clear preference for an increase in "progression-free survival"
(coef.: 1.087) and a reduction of "tumor-associated symptoms"(cough, shortness of
breath and pain); coef.: 1.090) was demonstrated, followed by the reduction of
side effects: "nausea and vomiting" (coef.: 0.605); "rash" (coef.: 0.432);
"diarrhea" (coef.: 0.427); and, "tiredness and fatigue" (coef.: 0.423). The "mode
of administration" was less important for participants (coef.: 0.141).
CONCLUSION: Preference measurement showed "progression-free survival" and "tumor
associated symptoms" had a significant influence on the treatment decision.
Subgroup analysis revealed that the importance of "progression-free survival"
increases with increased therapy experience. Based on the presented results
therapies can be designed, assessed and chosen on the basis of patient-oriented
findings. As such, more effective and efficient care of patients can be achieved
and benefits increased.
PMID- 25135769
TI - Recommendation of rotavirus vaccination and herd effect: a budget impact analysis
based on German health insurance data.
AB - The objective of this study was to assess the budget impact and health effects of
introducing rotavirus (RV) vaccination in Saxony, Germany, from a health
insurance perspective. Special emphasis is given to the herd effect. We analyzed
direct medical and non-medical costs of RV infection for Social Health Insurance
between 2007 and 2010 based on 360,000 routine data observations from the AOK
PLUS for children below 5 years of age. We compared the actual annual number of
RV cases (vaccination scenario) with the number derived from 2005 (no
vaccination, base case scenario). The vaccination coverage rate has increased
from 5% to 61% between 2007 and 2010. The number of RV cases decreased by 21%
from 32,274 in 2007 to 25,614 in 2010. Based on vaccination coverage, the total
cost savings per 1,000 children due to RV vaccination was estimated to be 39,686
Euros. The overall share of outpatient costs was 60%. Mean gross cost savings
were expected to be 304 Euros per avoided case. The net cost savings were
expected to be 19 Euros per avoided case. About 59% of total savings was due to
herd protection resulting from increasing vaccine rates. The herd effect per
avoided case increased with increasing vaccine coverage. Incidence of RV cases,
vaccination costs and days absent from work were sensitive parameters. This
retrospective analysis showed that the increase in RV vaccination coverage in
Saxony has been budget neutral if not cost saving for sick funds.
PMID- 25135771
TI - Physico-chemical properties and cytotoxic potential of Cordyceps sinensis
metabolites.
AB - This study was conducted to estimate the antioxidant activities, biochemical
properties and biological activities of one of the entomopathogenic fungi,
Cordyceps sinensis. Analysis of fungal metabolites indicated that the most
abundant free sugar was glucose; the highest component of organic acids was
citric acid from 10-day culture medium and the glutamate was the predominant
amino acid observed from 3-day culture medium. Maximum total polyphenols and
flavonoids were detected in the 15-day culture medium. For cytotoxicity test,
three cancer cell lines, HepG2 (liver), MCF-7 (breast) and A549 (lung) were used.
The IC50 values of the highest toxicity of HepG2 cell lines were observed from 10
day cultured medium, whereas the highest toxicity of MCF-7 and A549 was observed
on 5-day cultured medium. This is the first study reporting on the strong
antioxidant and cytotoxic potential of C. sinensis. Culture medium of C. sinensis
may thus be used as an effective antioxidant and anticancer treatment of natural
origin.
PMID- 25135770
TI - Trends in red blood cell transfusion and 30-day mortality among hospitalized
patients.
AB - BACKGROUND: Blood conservation strategies have been shown to be effective in
decreasing red blood cell (RBC) utilization in specific patient groups. However,
few data exist describing the extent of RBC transfusion reduction or their impact
on transfusion practice and mortality in a diverse inpatient population. STUDY
DESIGN AND METHODS: We conducted a retrospective cohort study using comprehensive
electronic medical record data from 21 medical facilities in Kaiser Permanente
Northern California. We examined unadjusted and risk-adjusted RBC transfusion and
30-day mortality coincident with implementation of RBC conservation strategies.
RESULTS: The inpatient study cohort included 391,958 patients who experienced
685,753 hospitalizations. From 2009 to 2013, the incidence of RBC transfusion
decreased from 14.0% to 10.8% of hospitalizations; this change coincided with a
decline in pretransfusion hemoglobin (Hb) levels from 8.1 to 7.6 g/dL. Decreased
RBC utilization affected broad groups of admission diagnoses and was most
pronounced in patients with a nadir Hb level between 8 and 9 g/dL (n = 73,057;
50.8% to 19.3%). During the study period, the standard deviation of risk-adjusted
RBC transfusion incidence across hospitals decreased by 44% (p < 0.001). Thirty
day mortality did not change significantly with declines in RBC utilization in
patient groups previously studied in clinical trials nor in other subgroups.
CONCLUSIONS: After the implementation of blood conservation strategies, RBC
transfusion incidence and pretransfusion Hb levels decreased broadly across
medical and surgical patients. Variation in RBC transfusion incidence across
hospitals decreased from 2010 to 2013. Consistent with clinical trial data, more
restrictive transfusion practice did not appear to impact 30-day mortality.
PMID- 25135772
TI - Neonatal lethality of neural crest cell-specific Rest knockout mice is associated
with gastrointestinal distension caused by aberrations of myenteric plexus.
AB - RE1-silencing transcription factor (REST), also known as NRSF (neuron-restrictive
silencer factor), is a well-known transcriptional repressor of neural genes. Rest
null mice have embryonic lethality which prevents further investigations of the
functions of the Rest gene in vivo. We studied neonatal but not embryonic
lethality that was characterized by gastrointestinal tract dilation in the neural
crest cell (NCC)-specific Rest conditional knockout (CKO) mice. While no
histological abnormalities except the thinning of the digestive tract as a
consequence of the gas accumulation were found in the digestive tract of the
mutant mice, they do not have proper gastric retention after oral dye
administration and the reduction of acetylcholinesterase (AChE) activity in NCC
derived myenteric plexus in the stomach was detected. High CO2 concentration in
the dilated digestive tract of the Rest CKO mice indicates a failure of gut
function by underdeveloped cholinergic transmission in the enteric nervous
system. The observed gastrointestinal distension phenotype provides a model for
understanding the genetic and molecular basis of NCC defects in humans.
PMID- 25135773
TI - Does MESNA application make sense in chronic otitis media surgery?
PMID- 25135774
TI - Delivering evidence-based treatments for child attention-deficit/hyperactivity
disorder (ADHD) in the context of parental ADHD.
AB - Behavioral parent training (BPT) and stimulant medications are efficacious
treatments for child attention-deficit/hyperactivity disorder (ADHD); however,
there is some evidence to suggest that parental ADHD may reduce the efficacy of
both treatment modalities. This review paper summarizes the literature related to
the evidence-based behavioral and pharmacological treatment of child ADHD in the
context of parental ADHD. We also review the literature on the effects of
treating parents' ADHD symptoms on parenting and child behavior outcomes.
Although the literature is small and inconsistent, studies suggest that
medicating parents' ADHD symptoms may or may not be sufficient in demonstrating
desired improvements in parenting and child behavioral outcomes. Therefore,
interventions targeting both parent and child ADHD, when both are present, are
likely needed to improve parent-child interactions and family functioning.
Ongoing studies using a multimodal approach are discussed.
PMID- 25135775
TI - Internally displaced "victims of armed conflict" in Colombia: the trajectory and
trauma signature of forced migration.
AB - While conflict-induced forced migration is a global phenomenon, the situation in
Colombia, South America, is distinctive. Colombia has ranked either first or
second in the number of internally displaced persons for 10 years, a consequence
of decades of armed conflict compounded by high prevalence of drug trafficking.
The displacement trajectory for displaced persons in Colombia proceeds through a
sequence of stages: (1) pre-expulsion threats and vulnerability, (2) expulsion,
(3) migration, (4) initial adaptation to relocation, (5) protracted resettlement
(the end point for most forced migrants), and, rarely, (6) return to the
community of origin. Trauma signature analysis, an evidence-based method that
elucidates the physical and psychological consequences associated with exposures
to harm and loss during disasters and complex emergencies, was used to identify
the psychological risk factors and potentially traumatic events experienced by
conflict-displaced persons in Colombia, stratified across the phases of
displacement. Trauma and loss are experienced differentially throughout the
pathway of displacement.
PMID- 25135776
TI - Strategies for successful aging: a research update.
AB - Population aging is an enormous public health issue and there is clear need for
strategies to maximize opportunities for successful aging. Many psychiatric
illnesses are increasingly thought to be associated with accelerated aging,
therefore emerging data on individual and policy level interventions that alter
typical aging trajectories are relevant to mental health practitioners. Although
the determinants and definition of successful aging remain controversial,
increasing data indicate that psychiatric illnesses directly impact biological
aging trajectories and diminish lifestyle, psychological, and socio-environmental
factors that seem to reduce risk of morbidity and mortality. Many interventions
designed to enhance the normal course of aging may be adjunctive approaches to
management of psychiatric illnesses. We highlight recent data on interventions
seeking to promote healthy aging, such as cognitive remediation, physical
activity, nutrition, and complementary and alternative treatments for older
people with and without psychiatric illnesses.
PMID- 25135777
TI - Determining the causes and consequences of nicotine dependence: emerging genetic
research methods.
AB - Tobacco use remains the leading cause of preventable death worldwide.
Establishing the genetic aetiology of tobacco use and dependence is an important
first step in understanding the neurobiological mechanisms of tobacco use, and in
turn the development of effective treatments. In addition, whilst the effects of
tobacco use on a broad range of physical illnesses (e.g. lung cancer, respiratory
disease, cardiovascular disease) are now well-established, the causal effects of
tobacco use on a number of other outcomes remains to be established. Determining
the causes and consequences of tobacco use therefore continues to be both a
scientific and a public health priority. Here we review emerging methods in
genetic research that allow stronger causal inferences to be drawn from
observational data.
PMID- 25135778
TI - Using stimulants to treat ADHD-related emotional lability.
AB - Emotional lability, or sudden strong shifts in emotion, commonly occurs in youth
with attention-deficit/hyperactivity disorder. Although these symptoms are
impairing and disruptive, relatively little research has addressed their
treatment, likely due to the difficulty of reliable and valid assessment.
Promising signals for symptom improvement have come from recent studies using
stimulants in adults, children and adolescents. Similarly, neuroimaging studies
have begun to identify neurobiological mechanisms underlying stimulants' impact
on emotion regulation capacities. Here, we review these recent clinical and
neuroimaging findings, as well as neurocognitive models for emotional lability in
ADHD, issues of relevance to prescribers and the important role of psychiatric
comorbidity with treatment choices.
PMID- 25135779
TI - Managing the risks of ADHD treatments.
AB - Pharmacotherapy of attention deficit-hyperactivity disorder (ADHD) is a well
established and effective treatment modality. However, ADHD medications are not
without side effects. Understanding the prevalence of adverse events and
effective management of risks associated with stimulants and other medications
used to treat ADHD is central to broad applicability and effective treatment.
This review discusses the literature on the prevalence of adverse events and
management strategies employed. We searched online MEDLINE/PubMed and Cochrane
databases for articles using several keywords relating to adverse events
associated with ADHD medication management. We discuss the relevant data on the
significance and prevalence of side effects and adverse events, highlight recent
updates in the field, and suggest approaches to clinical management.
PMID- 25135780
TI - Personality disorder classification: stuck in neutral, how to move forward?
AB - An "Alternative DSM-5 Model for Personality Disorders" was published in Sect. III
of DSM-5, while the identical categories and criteria from DSM-IV for the
personality disorders (PDs) are in Sect. II. Given strong shifts from categorical
diagnoses toward dimensional representations in psychiatry, how did the PDs end
up "stuck in neutral," with the flawed DSM-IV model perpetuated? This article
reviews factors that influenced the development of the new model and data to
encourage and facilitate its use by clinicians. These include recognizing 1) a
dimensional structure for psychopathology for which personality may be
foundational; 2) a consensus on the structure of normal and abnormal personality;
3) the clinical significance of personality; 4) PD-specific severity required to
establish disorder; 5) disruption, discontinuity, and perceived clinical utility
of the Alternative Model may not be problems; and 6) a way forward involving
collaborative research on neurobiological and psychosocial processes, treatment
planning, and outcomes.
PMID- 25135781
TI - Bereavement: course, consequences, and care.
AB - This paper discusses each of several potential consequences of bereavement.
First, we describe ordinary grief, followed by a discussion of grief gone awry,
or complicated grief (CG). Then, we cover other potential adverse outcomes of
bereavement, each of which may contribute to, but are not identical with, CG:
general medical comorbidity, mood disorders, post-traumatic stress disorder,
anxiety, and substance use.
PMID- 25135782
TI - Circadian clock and stress interactions in the molecular biology of psychiatric
disorders.
AB - Many psychiatric disorders are characterized by circadian rhythm abnormalities,
including disturbed sleep/wake cycles, changes in locomotor activity, and
abnormal endocrine function. Animal models with mutations in circadian "clock
genes" commonly show disturbances in reward processing, locomotor activity and
novelty seeking behaviors, further supporting the idea of a connection between
the circadian clock and psychiatric disorders. However, if circadian clock
dysfunction is a common risk factor for multiple psychiatric disorders, it is
unknown if and how these putative clock abnormalities could be expressed
differently, and contribute to multiple, distinct phenotypes. One possible
explanation is that the circadian clock modulates the biological responses to
stressful environmental factors that vary with an individual's experience. It is
known that the circadian clock and the stress response systems are closely
related: Circadian clock genes regulate the physiological sensitivity to and
rhythmic release of glucocorticoids (GC). In turn, GCs have reciprocal effects on
the clock. Since stressful life events or increased vulnerability to stress are
risk factors for multiple psychiatric disorders, including post-traumatic stress
disorder (PTSD), attention deficit hyperactivity disorder (ADHD), bipolar
disorder (BD), major depressive disorder (MDD), alcohol use disorder (AUD) and
schizophrenia (SCZ), we propose that modulation of the stress response is a
common mechanism by which circadian clock genes affect these illnesses.
Presently, we review how molecular components of the circadian clock may
contribute to these six psychiatric disorders, and present the hypothesis that
modulation of the stress response may constitute a common mechanism by which the
circadian clock affects multiple psychiatric disorders.
PMID- 25135783
TI - The significance of mixed states in depression and mania.
AB - The DSM-5 definition of mixed features "specifier" of manic, hypomanic and major
depressive episodes captures sub-syndromal non-overlapping symptoms of the
opposite pole, experienced in bipolar (I, II, and not otherwise specified) and
major depressive disorders. This combinatory model seems to be more appropriate
for less severe forms of mixed state, in which mood symptoms are prominent and
clearly identifiable. Sub-syndromal depressive symptoms have been frequently
reported to co-occur during mania. Similarly, manic or hypomanic symptoms during
depression resulted common, dimensionally distributed, and recurrent. The
presence of mixed features has been associated with a worse clinical course and
high rates of comorbidities including anxiety, personality, alcohol and substance
use disorders and head trauma or other neurological problems. Finally, mixed
states represent a major therapeutic challenge, especially when you consider that
these forms tend to have a less favorable response to drug treatments and require
a more complex approach than non-mixed forms.
PMID- 25135784
TI - Sleep and substance use disorders: an update.
AB - Substance use disorders (SUD) are common and individuals who suffer from them are
prone to relapse. One of the most common consequences of the use of and
withdrawal from substances of abuse is sleep disturbance. Substances of abuse
affect sleep physiology, including the neurotransmitter systems that regulate the
sleep-wake system. Emerging research now highlights an interactive effect between
sleep disorders and substance use. New findings in alcohol and sleep research
have utilized sophisticated research designs and expanded the scope of EEG and
circadian rhythm analyses. Research on marijuana and sleep has progressed with
findings on the effects of marijuana withdrawal on objective and subjective
measures of sleep. Treatment studies have focused primarily on sleep in alcohol
use disorders. Therapies for insomnia in cannabis disorders are needed. Future
research is poised to further address mechanisms of sleep disturbance in
alcoholics and the effect of medical marijuana on sleep and daytime functioning.
PMID- 25135786
TI - Sentinel node mapping using hysteroscopic injection of indocyanine green and
laparoscopic near-infrared fluorescence imaging in endometrial cancer staging.
AB - Herein is presented a technique for minimally invasive sentinel node mapping. The
patient had apparently early stage endometrial cancer. Sentinel node mapping was
performed using a hysteroscopic injection of indocyanine green followed by
laparoscopic sentinel node detection via near-infrared fluorescence. This
technique ensures delineation of lymphatic drainage from the tumor area, thus
achieving accurate detection of sentinel nodes.
PMID- 25135785
TI - Species and gene divergence in Littorina snails detected by array comparative
genomic hybridization.
AB - BACKGROUND: Array comparative genomic hybridization (aCGH) is commonly used to
screen different types of genetic variation in humans and model species. Here, we
performed aCGH using an oligonucleotide gene-expression array for a non-model
species, the intertidal snail Littorina saxatilis. First, we tested what types of
genetic variation can be detected by this method using direct re-sequencing and
comparison to the Littorina genome draft. Secondly, we performed a genome-wide
comparison of four closely related Littorina species: L. fabalis, L. compressa,
L. arcana and L. saxatilis and of populations of L. saxatilis found in Spain,
Britain and Sweden. Finally, we tested whether we could identify genetic
variation underlying "Crab" and "Wave" ecotypes of L. saxatilis. RESULTS: We
could reliably detect copy number variations, deletions and high sequence
divergence (i.e. above 3%), but not single nucleotide polymorphisms. The overall
hybridization pattern and number of significantly diverged genes were in close
agreement with earlier phylogenetic reconstructions based on single genes. The
trichotomy of L. arcana, L. compressa and L. saxatilis could not be resolved and
we argue that these divergence events have occurred recently and very close in
time. We found evidence for high levels of segmental duplication in the Littorina
genome (10% of the transcripts represented on the array and up to 23% of the
analyzed genomic fragments); duplicated genes and regions were mostly the same in
all analyzed species. Finally, this method discriminated geographically distant
populations of L. saxatilis, but we did not detect any significant genome
divergence associated with ecotypes of L. saxatilis. CONCLUSIONS: The present
study provides new information on the sensitivity and the potential use of
oligonucleotide arrays for genotyping of non-model organisms. Applying this
method to Littorina species yields insights into genome evolution following the
recent species radiation and supports earlier single-gene based phylogenies.
Genetic differentiation of L. saxatilis ecotypes was not detected in this study,
despite pronounced innate phenotypic differences. The reason may be that these
differences are due to single-nucleotide polymorphisms.
PMID- 25135787
TI - Characterization of glycerophosphoethanolamine ethanolaminephosphodiesterase from
Streptomyces sanglieri.
AB - Streptomyces sanglieri extracellularly produces a glycerophosphoethanolamine
ethanolaminephosphodiesterase (GPE-EP). The gene encoding the enzyme was found to
consist of a 2124-bp ORF, which codes for an N-terminal 48 residue signal peptide
required for secretion and a 660 amino acid mature protein with a calculated
molecular mass of 72,918 Da. The maximum activity for sn-glycero-3
phosphoethanolamine (GPE) was found at pH 8.4 and 65 degrees C in the presence of
0.1% (w/v) Triton X-100. The enzyme was activated in the presence of 2 mM EDTA;
however, Zn(2+) remarkably inhibited activity. During the hydrolysis of GPE at 65
degrees C and pH 8.4, the apparent Vmax, turnover number (kcat) and Km were
determined to be 0.430 mmol min(-1) mg-protein(-1), 522 s(-1) and 0.785 mM,
respectively. The enzyme exhibited specificity toward GPE and hydrolyzed
ethanolamine-type substrates such as 1,2-dihexanoyl-sn-glycero-3
phosphoethanolamine, lysophosphatidylethanolamine and ethanolamine
lysoplasmalogen, but not 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine.
Moreover, the enzyme showed no activity toward other phospholipids, such as
glycerophospholipids and plasmalogens, and sn-glycero-3-phosphodiesters except
for sn-glycero-3-phosphoglycerol, suggesting that GPE-EP is not a phospholipase C
(PLC). However, the amino acid sequence of GPE-EP shows 86% identity to that of
PLC from Streptomyces sp. SirexAA-E (UniProt accession no. G2NFN1). Recombinant
GPE-EP was functionally expressed in Escherichia coli using pET-24a(+). GPE
hydrolysis by GPE-EP may represent a new pathway for phosphatidylethanolamine
metabolism.
PMID- 25135788
TI - Expression profile based gene clusters for ischemic stroke detection.
AB - In microarray studies alterations in gene expression in circulating leukocytes
have shown utility for ischemic stroke diagnosis. We studied forty candidate
markers identified in three gene expression profiles to (1) quantitate individual
transcript expression, (2) identify transcript clusters and (3) assess the
clinical diagnostic utility of the clusters identified for ischemic stroke
detection. Using high throughput next generation qPCR 16 of the 40 transcripts
were significantly up-regulated in stroke patients relative to control subjects
(p<0.05). Six clusters of between 5 and 7 transcripts were identified that
discriminated between stroke and control (p values between 1.01e-9 and 0.03). A 7
transcript cluster containing PLBD1, PYGL, BST1, DUSP1, FOS, VCAN and FCGR1A
showed high accuracy for stroke classification (AUC=0.854). These results
validate and improve upon the diagnostic value of transcripts identified in
microarray studies for ischemic stroke. The clusters identified show promise for
acute ischemic stroke detection.
PMID- 25135789
TI - Expression of the lymphatic marker podoplanin (D2-40) in human fetal eyes.
AB - During human ocular development, expression of proteins varies in different
maturation stages. This study aims to characterize structures in human fetal eyes
stained by the lymphatic marker podoplanin (D2-40) with emphasis on the stage of
maturation and the presence of intraocular lymphatic structures. Formalin-fixed
paraffin-embedded eyes from 40 human fetuses between 10 and 38 weeks of gestation
(WoG) were investigated. Immunohistochemical stains were performed for D2-40,
LYVE-1 as a secondary lymphatic marker, and CD34 as a control for endothelial
reactivity. A semiquantitative analysis of antigen expression in different
segments of the eye was performed by light microscopy. The intensity of antigen
expression was graded with a score ranging from 0 to 3. Podoplanin expression was
found with a variable intensity in 97.5% of the eyes, in particular in lymphatic
vessels of the conjunctiva (n = 26), conjunctival and corneal epithelium (n =
33), corneal endothelium (n = 4), trabecular meshwork (n = 28), and optic nerve
sheaths (n = 23). A slight, equivocal staining reaction was noted in the choroid
(n = 14). There was a correlation of antigen reactivity and the gestational age
for corneal endothelial reactivity in earlier gestational stages (p = 0.003) and
trabecular meshwork in older eyes (p = 0.031). D2-40 positive Muller cells were
detected in two eyes >=32 WoG. Thus, aside from conjunctival lymphatic vessels,
podoplanin was expressed in several structures of the human fetal eye and the
ocular adnexae at different gestational stages. Podoplanin positive structures
were also found in the choroid and the chamber angle. However, lymphatic vessels
or its progenitors could not be unequivocally identified in intraocular
structures during 10-38 weeks of gestation. There is no evidence from our data
that transient intraocular lymphactics develop in the fetal eye between 10 and 38
weeks of gestation.
PMID- 25135790
TI - Micro-fractional epidermal powder delivery for improved skin vaccination.
AB - Skin vaccination has gained increasing attention in the last two decades due to
its improved potency compared to intramuscular vaccination. Yet, the technical
difficulty and frequent local reactions hamper its broad application in the
clinic. In the current study, micro-fractional epidermal powder delivery (EPD) is
developed to facilitate skin vaccination and minimize local adverse effects. EPD
is based on ablative fractional laser or microneedle treatment of the skin to
generate microchannel (MC) arrays in the epidermis followed by topical
application of powder drug/vaccine-coated array patches to deliver drug/vaccine
into the skin. The novel EPD delivered more than 80% sulforhodamine b (SRB) and
model antigen ovalbumin (OVA) into murine, swine, and human skin within 1h. EPD
of OVA induced anti-OVA antibody titer at a level comparable to intradermal (ID)
injection and was much more efficient than tape stripping in both delivery
efficiency and immune responses. Strikingly, the micro-fractional delivery
significantly reduced local side effects of LPS/CpG adjuvant and BCG vaccine,
leading to complete skin recovery. In contrast, ID injection induced severe local
reactions that persisted for weeks. While reducing local reactogenicity, EPD of
OVA/LPS/CpG and BCG vaccine generated a comparable humoral immune response to ID
injection. EPD of vaccinia virus encoding OVA induced significantly higher and
long-lasting interferon gamma-secreting CD8+ T cells than ID injection. In
conclusion, EPD represents a promising technology for needle-free, painless skin
vaccination with reduced local reactogenicity and at least sustained
immunogenicity.
PMID- 25135791
TI - Relations between acoustic cavitation and skin resistance during intermediate-
and high-frequency sonophoresis.
AB - Enhanced skin permeability is known to be achieved during sonophoresis due to
ultrasound-induced cavitation. However, the mechanistic role of cavitation during
sonophoresis has been extensively investigated only for low-frequency (LFS, <100
kHz) applications. Here, mechanisms of permeability-enhancing stable and inertial
cavitation were investigated by passively monitoring subharmonic and broadband
emissions arising from cavitation isolated within or external to porcine skin in
vitro during intermediate- (IFS, 100-700 kHz) and high-frequency sonophoresis
(HFS, >1 MHz). The electrical resistance of skin, a surrogate measure of the
permeability of skin to a variety of compounds, was measured to quantify the
reduction and subsequent recovery of the skin barrier during and after exposure
to pulsed (1 second pulse, 20% duty cycle) 0.41 and 2.0 MHz ultrasound over a
range of acoustic powers (0-21.7 W) for 30 min. During IFS, significant skin
resistance reductions and acoustic emissions from cavitation were measured
exclusively when cavitation was isolated outside of the skin. Time-dependent skin
resistance reductions measured during IFS correlated significantly with
subharmonic and broadband emission levels. During HFS, significant skin
resistance reductions were accompanied by significant acoustic emissions from
cavitation measured during trials that isolated cavitation activity either
outside of skin or within skin. Time-dependent skin resistance reductions
measured during HFS correlated significantly greater with subharmonic than with
broadband emission levels. The reduction of the skin barrier due to sonophoresis
was reversible in all trials; however, effects incurred during IFS recovered more
slowly and persisted over a longer period of time than HFS. These results
quantitatively demonstrate the significance of cavitation during sonophoresis and
suggest that the mechanisms and post-treatment longevity of permeability
enhancement due to IFS and HFS treatments are different.
PMID- 25135793
TI - Addition of recommendations for the use of recombinant human thrombomodulin to
the "Expert consensus for the treatment of disseminated intravascular coagulation
in Japan".
PMID- 25135792
TI - Intercalating quaternary nicotinamide-based poly(amido amine)s for gene delivery.
AB - In the development of potent polymeric gene carriers for gene therapy, a good
interaction between the polymer and the nucleotide is indispensable to form small
and stable polyplexes. Polymers with relatively high cationic charge density are
frequently used to provide these interactions, but high cationic charge is
usually associated with severe cytotoxicity. In this study an alternative,
nucleotide specific binding interaction based on intercalation was investigated
to improve polymer/pDNA complex formation. For this purpose bioreducible
poly(amido amine) copolymers (p(CBA-ABOL/Nic)) were synthesized with different
degrees of intercalating quaternary nicotinamide (Nic) groups and amide
substituted derivatives in their side chains. The quaternary nicotinamide group
was chosen as intercalating moiety because this group is part of the naturally
occurring NAD+ coenzyme and is therefore expected to be non-toxic and non
carcinogenic. The presence of the quaternary nicotinamide moieties in the
poly(amido amine) copolymers showed to effectively promote self-assembled
polyplex formation already at low polymer/DNA ratios and results in decreased
polyplex size and increased stability of the polyplexes. Furthermore, in contrast
to the primary amine functionalized analogs the quaternary nicotinamide polymers
showed to be non-hemolytic, indicating their compatibility with cell membranes.
Polymers with 25% of Nic in the side chains induced GFP expressions of about 4-5
times that of linear PEI, which is comparable with p(CBA-ABOL), the parent PAA
without Nic, but at a two- to fourfold lower required polymer dose. N-phenylation
of the nicotinamide functionality even further reduces the required polymer dose
to form stable polyplexes, which is a major improvement for these kinds of
cationic polymers.
PMID- 25135794
TI - Treatment patterns of venous thromboembolism in a real-world population: the Q
VTE study cohort.
AB - BACKGROUND: Few studies have assessed treatment patterns of acute venous
thromboembolism (VTE) in a real-world population. We aimed to describe
anticoagulant treatment patterns for acute VTE using healthcare databases of
Quebec, Canada. METHODS: We used linked healthcare databases of the province of
Quebec, Canada to identify all incident cases of deep vein thrombosis (DVT) and
pulmonary embolism (PE) between 2000 and 2009. We formed two patient cohorts, one
with definite cases (definite VTE cohort, N=40,776) and the other including cases
with definite or probable VTE (any VTE cohort, N=54,803) that were followed until
death, end of health coverage, or end of study (December 31, 2009). RESULTS: In
the definite cohort, 73.6% of subjects were dispensed an anticoagulant following
the diagnosis of VTE. Of those who were dispensed a vitamin K antagonist (VKA),
median duration of use was 61days (interquartile range 89). VKA initiation was
more likely in patients with pulmonary embolism than deep vein thrombosis alone
(HR 1.62, 95% CI (1.58-1.66)). Among outpatients, those managed initially in the
outpatient setting were less likely to initiate VKA therapy (HR 0.75, 95% CI
(0.68-0.77)), while those requiring admission to hospital for VTE management were
more likely to initiate (HR 1.81, 95% CI (1.76-1.87)). Findings were similar in
the any VTE cohort. CONCLUSION: Our study describes VTE treatment patterns in a
real-world setting and suggests that there may be important gaps. These may
include significant numbers of patients who did not initiate oral anticoagulant
therapy, particularly in the outpatient setting, and shorter duration of oral
anticoagulant use than recommended.
PMID- 25135795
TI - Increased activation of blood coagulation in pregnant women with the Factor V
Leiden mutation.
AB - BACKGROUND: The risk of venous thromboembolism is enhanced in pregnant carriers
of the Factor V Leiden mutation. The primary aim of the study was to compare
prothrombin fragments 1+2, soluble fibrin and D-dimer levels in pregnant Factor V
Leiden mutation carriers with those in non-carriers. Secondary aims were to
evaluate whether these biomarkers could predict placenta-mediated complications
or venous thromboembolism, and to study blood coagulation after caesarean section
with thromboprophylaxis and after vaginal delivery without thromboprophylaxis.
MATERIAL/METHODS: Prothrombin fragments 1+2, soluble fibrin and D-dimer levels
were studied longitudinally in 476 carriers with singleton pregnancies from
gestational weeks 23-25 until 8-10 weeks postpartum. RESULTS: Prothrombin
fragments 1+2 and D-dimer levels gradually increased during pregnancy. D-dimer
levels were higher in carriers, both during pregnancy and puerperium, compared to
non-carriers. D-dimer levels above 0.5mg/l were found in about 30% and 20% of the
heterozygous carriers at 4-5 and 8-10 weeks postpartum, respectively. Soluble
fibrin levels were mainly unchanged during pregnancy, with no difference between
carriers and non-carriers. Biomarker levels were similar in carriers with
uncomplicated and complicated pregnancies. CONCLUSION: Higher D-dimer levels
indicate increased blood coagulation and fibrinolysis activity in carriers. The
high proportion of carriers with D-dimer levels exceeding 0.5mg/l postpartum must
be considered when assessing the probability of venous thromboembolism. Large
overlaps in biomarker levels in normal and complicated pregnancies suggest that
these biomarkers cannot be used as predictors. Thromboprophylaxis following
caesarean section may prevent increased activation of blood coagulation.
PMID- 25135796
TI - Global platelet hyperreactivity and elevated C-reactive protein levels predict
long term mortality in STEMI patients.
AB - BACKGROUND: Data on long term - more than 1-year - prognostic value of global
platelet reactivity (G-HPR) - by adenosine diphosphate (ADP) and arachidonic acid
(AA) - in patients with STEMI undergoing PCI are limited. High C-reactive protein
(CRP) levels have been suggested to be associated with post-PCI atherothrombotic
events. Our aim was to evaluate the long-term prognostic impact of G-HPR and CRP
levels in STEMI patients. METHODS AND RESULTS: We evaluated 494 STEMI patients
(366 M/128 F; age: 65.8 +/- 12.4 yrs) undergoing PCI with stent implantation. At
a median follow-up of 2.3 years (1.09-4.06), in 58 patients we documented
cardiovascular death (11.7%). Platelet reactivity was assessed by light
transmission aggregometry by 1mM AA (AA-LTA) and 10 microM ADP (ADP-LTA). By the
ROC curve analysis, 17%, 52% and 12 mg/L were found to be the values of AA-LTA,
ADP-LTA and CRP associated with the highest specificity and sensitivity for
death. G-HPR was defined as the presence of both AA-LTA >= 17% and ADP-LTA >=
52%. At Cox regression analysis adjusted for age, sex, cardiovascular risk
factors, multivessel disease, ejection fraction, renal insufficiency, G-HPR and
elevated CRP levels were associated with long-term mortality [HR=1.78 (95%CI 1.04
3.03), p=0.036 and HR=2.91 (1.54-5.52, p=0.001), respectively]. The contemporary
presence of G-HPR and elevated CRP levels was associated with the highest risk of
death [HR=5.1 (95%CI 1.9-13.4), p=0.001]. CONCLUSION: G-HPR and CRP are
independent long-term prognostic markers in STEMI patients. The contemporary
presence of G-HPR and CRP identifies a subgroup of patients at significantly
higher risk of cardiovascular death.
PMID- 25135797
TI - Sri Lankan cassava mosaic virus replication associated protein (Rep) triggers
transposition of IS426 in Agrobacterium.
AB - We report a high rate of IS426 transposition in Agrobacterium tumefaciens in the
presence of the Sri Lankan cassava mosaic virus (SLCMV) replication associated
protein gene (Rep). Upon conjugal transfer of the binary plasmid pCam-SLCMV-Rep
with the SLCMV Rep gene in the sense orientation under the transcriptional
control of the Cauliflower mosaic virus (CaMV) 35S promoter into the A.
tumefaciens vir helper strain EHA105, the binary plasmid size increased in all 15
transconjugants studied. Southern blot analysis of the transconjugants with the
binary plasmid probe revealed that the 35S promoter and its proximal sequences in
the T-DNA were rearranged. The rearranged sequences harboured the 1.3-kb IS426
element of A. tumefaciens. Conjugal mobilisation of the binary plasmid pCam-SLCMV
asRep, with the SLCMV Rep gene in antisense orientation, did not cause DNA
rearrangement in EHA105. A mutated SLCMV Rep, in which a frame shift mutation
caused retention of only 27 of the 351 amino acids, did not cause IS426
transposition in A. tumefaciens. These findings show that the multifunctional
begomoviral Rep protein of SLCMV triggers transposition of IS426 in
Agrobacterium.
PMID- 25135798
TI - Use of prescription drugs and future delinquency among adolescent offenders.
AB - Non-medical use of prescription drugs (NMUPD) by adolescents is a significant
public health concern. The present study investigated the profile of NMUPD in
1349 adolescent offenders from the Pathways to Desistance project, and whether
NMUPD predicted future delinquency using longitudinal data. Results indicated
that increased frequency and recency of NMUPD in adolescent offenders are related
to some demographic factors, as well as increased risk for violence exposure,
mental health diagnoses, other drug use, and previous delinquency, suggesting
that severity of NMUPD is important to consider. However, ANCOVA analyses found
that NMUPD was not a significant predictor of drug-related, non-aggressive, or
aggressive delinquency 12 months later beyond other known correlates of
delinquency. Age, sex, exposure to violence, lower socioeconomic status, more
alcohol use, and having delinquency histories were more important than NMUPD in
predicting future delinquency. These findings suggest that although NMUPD is an
important risk factor relating to many correlates of delinquency, it does not
predict future delinquency beyond other known risk factors.
PMID- 25135799
TI - Refugees, humanitarian aid and the right to decline vaccinations.
AB - Recent instances of governments and others refusing humanitarian assistance to
refugees and IDPs (internally-displaced persons) unless they agreed to polio
immunization for their children raise difficult ethical challenges. The authors
argue that states have the right and a responsibility to require such
vaccinations in instances where the serious vaccine-preventable disease(s) at
issue threaten others, including local populations, humanitarian workers, and
others in camps or support settings.
PMID- 25135801
TI - Using the Peng flap for a wide dorsal nasal defect.
AB - Reconstructions of large surgical defects of the central part of the nose pose a
challenge for the surgeon due to its cosmetically prominent location. Treatment
options include second intention healing, full-thickness skin grafts and various
local flaps. In the present case the "Peng flap" was used for the reconstruction
of a 3.1 * 7 cm sized deep defect of the convex curve of the central nasal area
in a 66-year-old woman. The Peng flap was performed as single-stage procedure
without complications. Good cosmetic outcome was provided by the use of adjacent
skin from the lax perinasal area, the placement of the scar lines between facial
cosmetic units, and the excellent tissue match for the sebaceous nasal skin.
Considering the few complications of a single-stage procedure associated with an
excellent aesthetic outcome, the Peng flap should be considered not only as an
effective choice for reconstruction of the cosmetically complex midline nasal tip
but also the convex curve of the central nose.
PMID- 25135800
TI - Motives for participating in a web-based nutrition cohort according to
sociodemographic, lifestyle, and health characteristics: the NutriNet-Sante
cohort study.
AB - BACKGROUND: In traditional epidemiological studies, participants are likely
motivated by perceived benefits, feelings of accomplishment, and belonging. No
study has explored motives for participation in a Web-based cohort and the
associated participant characteristics, although such information is useful for
enhancing recruitment and improving cohort retention. OBJECTIVE: We aimed to
evaluate the relationships between motives for participation and
sociodemographic, health, and lifestyle characteristics of participants in the
NutriNet-Sante Web-based cohort, designed to identify nutritional risk or
protective factors for chronic diseases. METHODS: The motives for participation
were assessed using a specifically developed questionnaire administered
approximately 2 years after baseline. A total of 6352 completed the motives
questionnaire (43.34%, 6352/15,000 randomly invited cohort participants). We
studied the associations between motives (dependent variables) and individual
characteristics with multivariate multinomial logistic regression models
providing odds ratios and 95% confidence intervals. RESULTS: In total, 46.45%
(2951/6352) of participants reported that they would not have enrolled if the
study had not been conducted on the Internet, whereas 28.75% (1826/6352) were not
sure. Men (OR 1.21, 95% CI 1.04-1.42), individuals aged 26-35 years (OR 1.51, 95%
CI 1.20-1.91), and obese participants (OR 1.30, 95% CI 1.02-1.65) were more
inclined to be motivated by the Internet aspect. Compared with younger adults and
managerial staff, individuals >55 years (OR 0.60, 95% CI 0.48-0.45) and
employees/manual workers were less likely motivated by the Internet aspect (OR
0.77, 95% CI 0.63-0.92). Regarding reasons for participation, 61.37% (3898/6352)
reported participating to help advance public health research on chronic disease
prevention; 22.24% (1413/6352) to help advance nutrition-focused research; 6.89%
(438/6352) in response to the call from the media, after being encouraged by a
close friend/associate, or a medical provider. Individuals >45 years (vs younger
participants) were more likely (OR 1.62, 95% CI 1.07-2.47), whereas overweight
and obese participants (vs nonobese participants) were less likely to participate
in the study for reasons related to helping public health research on chronic
disease prevention (OR 0.72, 95% CI 0.58-0.89; OR 0.62, 95% CI 0.46-0.84;
respectively). Exclusive public funding of the study was important for 67.02%
(4257/6352) of the participants. Men (OR 1.37, 95% CI 1.17-1.61) and persons >55
years (OR 1.97, 95% CI 1.57-2.47) were more likely to consider the exclusive
public funding as very important. CONCLUSIONS: The use of the Internet, the
willingness to help advance public health research, and the study being publicly
funded were key motives for participating in the Web-based NutriNet-Sante cohort.
These motives differed by sociodemographic profile and obesity, yet were not
associated with lifestyle or health status. These findings can help improve the
retention strategies in Web-based cohorts, particularly during decisive study
periods when principal exposure information is collected.
PMID- 25135802
TI - Statin potency, LDL receptors and new onset diabetes.
PMID- 25135803
TI - Effectiveness of pharmacist intervention in patients with chronic kidney disease.
AB - BACKGROUND: Collaboration between pharmacists and physicians in the care of
patients with chronic kidney disease (CKD) may improve the quality of drug dosage
regimens that require adjustment according to the renal function. OBJECTIVE: To
demonstrate that the intervention of a pharmacist in a monitoring program for
patients with CKD improves the outcome of renal function in these patients.
Setting A 330-bed regional referral hospital in the city of Murcia (Spain).
METHOD: All patients with CKD and taking nephrotoxic medication admitted to the
internal medicine service were included in the study. Depending on the department
of the hospital to which the patients were admitted, they were assigned to an
intervention or control group. In the control group, the renal function at the
time of admission and discharge was measured. In the intervention group, in
addition to measuring kidney function at the time of admission and at discharge,
the patients were followed daily and recommendation for dose adjustment were made
when nephrotoxic drugs were not properly dosed. MAIN OUTCOME MEASURE: Glomerular
filtration rate on admission and at discharge. RESULTS: A total of 249 patients
were included in the study, 124 in the control group and 125 in the intervention
group. Significant differences were noted when comparing creatinine clearance
(CrCl) between discharge and admission in both the control and intervention
groups (5.1 +/- 0.9 vs. 6.4 +/- 1.0 p < 0.01). In a comparison of the observed
improvement in the two groups, we found significant differences in adjusted
relative CrCl according to sex, age and stage (19.9 [1.2-38.5] p < 0.05). When
the disease was analyzed by stage, we observed significant differences that
favored the intervention group in regards CrCl (3.1 +/- 2.1 vs. 7.9 +/- 3.8 p <
0.05) and relative CrCl (16.1 +/- 10.3 vs. 36.6 +/- 16.7) in stages 4-5. The rate
of acceptance of the pharmacists' recommendations was 74 %. CONCLUSION: The
implementation of a monitoring program for CKD patients was effective in the
group in which monitoring was conducted, especially in patients with more
advanced stage of CKD.
PMID- 25135804
TI - Modified labels for long-term medications: influences on adherence, comprehension
and preferences in Malaysia.
AB - BACKGROUND: Inability to read instructions on drug labels has been identified
among the Malaysian population since 1990's. OBJECTIVE: To assess the impact of
font-enlarged and pictogram-incorporated labels used for long-term medications on
patients' adherence, comprehension and preferences. SETTING: Outpatient pharmacy
in one of the major general hospitals across Northern Malaysia. METHOD: This was
a three-arm, randomized controlled trial. Outpatients with refill prescriptions
of selected oral antihypertensive or antidiabetic medications were screened for
eligibility. They were randomly allocated with standard (n = 35), font-enlarged
(n = 40) or pictogram-incorporated (n = 35) labels. Assessment of baseline
adherence scores using the 8-item Morisky Medication Adherence Scale,
comprehension scores using a structured questionnaire and preferences was
conducted upon recruitment. Follow-up telephone interviews were conducted after 4
weeks. MAIN OUTCOME MEASURE: The changes of patients' adherence and comprehension
scores and their preferences. RESULTS: Within-group comparisons demonstrated an
increase of total adherence scores after 4 weeks in all three groups (mean
changes 0.35, 0.58 and 0.67; p = 0.029, 0.013 and 0.011, respectively). The
repeatedly measured total comprehension score of pictogram-incorporated label
group was significantly higher than baseline (mean change 0.37, p = 0.010). Two
intervention groups obtained significantly higher scores for few items in both
adherence and comprehension measurements after 4 weeks as compared with
baselines. As indicated by F tests, three groups did not significantly differ in
the changes of both total adherence and comprehension scores (p = 0.573 and
0.069, respectively) with the subjects' age adjusted. Elderlies and those with a
higher number of morbidity preferred pictogram-incorporated label over font
enlarged label. CONCLUSION: We did not find a significant change of both
adherence and comprehension levels after the introduction of modified medication
labels. However, on the basis of within-group comparisons, they may have positive
influences on certain aspects of patients' adherence and comprehension.
Variations in preferences may reflect the unique need of different subgroups in
receiving written medication instructions.
PMID- 25135805
TI - Impact of community pharmacist intervention discussing patients' beliefs to
improve medication adherence.
AB - BACKGROUND: Adherence to evidence based medicines in patients who have
experienced a myocardial infarction remains low. Individual's beliefs towards
their medicines are a strong predictor of adherence and may influence other
factors that impact on adherence. OBJECTIVE: To investigate if community
pharmacists discussing patients' beliefs about their medicines improved
medication adherence at 12 months post myocardial infarction. SETTING: This study
included 200 patients discharged from a public teaching hospital in Queensland,
Australia, following a myocardial infarction. Patients were randomised into
intervention (n = 100) and control groups (n = 100) and followed for 12 months.
METHOD: All patients were interviewed between 5 to 6 weeks, at 6 and 12 months
post discharge by the researcher using the repertory grid technique. This
technique was used to elicit the patient's individualised beliefs about their
medicines for their myocardial infarction. In the intervention group, patients'
beliefs about their medicines were communicated by the researcher to their
community pharmacist. The pharmacist used this information to tailor their
discussion with the patient about their medication beliefs at designated time
points (3 and 6 months post discharge). The control group was provided with usual
care. MAIN OUTCOME MEASURE: The difference in non-adherence measured using a
medication possession ratio between the intervention and control groups at 12
months post myocardial infarction. RESULTS: There were 137 patients remaining in
the study (intervention group n = 72, control group n = 65) at 12 months. In the
intervention group 29 % (n = 20) of patients were non-adherent compared to 25 %
(n = 16) of patients in control group. CONCLUSION: Discussing patients' beliefs
about their medicines for their myocardial infarction did not improve medication
adherence. Further research on patients beliefs should focus on targeting non
adherent patients whose reasons for their non-adherence is driven by their
medication beliefs.
PMID- 25135806
TI - Antimicrobial stewardship and linezolid.
AB - BACKGROUND: Since 2002, linezolid, the first representative of the oxazolidinone
class, has been widely prescribed, sometimes outside of approved indications.
However, several cases of clinical outbreaks due to linezolid-resistant organisms
have been reported, and its relatively high cost represents an economic challenge
for hospital settings. OBJECTIVES: The aim of this study was to assess the impact
of different actions conducted by an antimicrobial stewardship team (AST) to
control over-prescription of linezolid with regard to the defined daily dose
(DDD) per 1,000 inhabitants per day. SETTING: This work was conducted in a 1,495
bed hospital from 2009 to 2013. An AST, gathering the departments of pharmacy,
microbiology, and infectious diseases, assessed the pertinence of linezolid use
and associated effect on the prescriber. METHOD: A retrospective study was
conducted throughout 2009. Three different evaluations were prospectively carried
out, each for 3 months, between 2011 and 2013. MAIN OUTCOME MEASURE: The
indicators chosen to monitor the consumption of linezolid were the DDD per 1,000
inhabitants per day, which enabled a comparison to be made between hospitals from
2004 to 2012, and of the pertinence of its prescription by different departments.
RESULTS: From 2009 to 2013, 239 patients were evaluated through three 3-month
stages. Prescriptions were for off-label use in 45 % of cases. Prescriptions were
considered appropriate in 60 % of cases. Unsuitable treatment was either modified
or discontinued (62 and 38 % of cases, respectively). Mean duration of linezolid
treatment was 8 days, i.e. below the national mean duration reported in the
literature. To highlight the impact of action taken by the team, a consensual
strategy to treat ventilator-acquired pneumonia was elaborated with principal
prescribers. Throughout the study, the mean DDD per 1,000 inhabitants per day
increased very slowly and was lower than the eleven other French hospitals, which
were secondarily included in this study. CONCLUSION: The multidisciplinary
approach that was adopted for therapeutic education and delivery control led to
an improvement in the proper use of linezolid. Similar strategy should be
extended to other antimicrobial agents, such as carbapenems, for which both cost
and risk of resistance emergence are of major concern.
PMID- 25135807
TI - Intraocular pressure effects of common topical steroids for post-cataract
inflammation: are they all the same?
AB - The efficacy of topical corticosteroids as ocular anti-inflammatory agents
following cataract surgery is well-documented. They also help to prevent a number
of complications associated with post-operative ocular inflammation, including
corneal edema and cystoid macular edema. However, topical corticosteroids are
associated with side effects, such as increased intraocular pressure (IOP).
Indeed, corticosteroid-induced ocular hypertension and the potential for steroid
induced glaucoma remain the leading drawbacks of topical corticosteroid therapy.
Some individuals are known to experience a high degree of IOP elevation with low
doses or short durations of treatment with topical corticosteroids. Careful
monitoring of IOP in such individuals is essential. Few randomized, controlled
studies are available on the comparative safety and efficacy of common topical
corticosteroids in the treatment of post-operative ocular inflammation.
Furthermore, the lack of consistent reporting criteria for clinically significant
IOP increases across clinical studies makes meaningful comparisons among
corticosteroids difficult. This review aims to examine data from available
published studies, including studies in steroid responders, to determine whether
topical corticosteroids are the same in terms of their effect on IOP. Early
generation corticosteroids, such as dexamethasone and prednisolone, are more
likely to result in clinically significant increases in IOP. Newer
corticosteroids, such as rimexolone and the retro-metabolically designed
corticosteroid, loteprednol etabonate, offer similar anti-inflammatory efficacy
to older corticosteroids with less effect on IOP. However, randomized controlled
trials of newer corticosteroids are needed. The proportion of patients exhibiting
an increase of >=10 mmHg IOP in clinical studies has emerged as the most
clinically relevant parameter for ophthalmologists to consider when deciding on
which topical corticosteroid to use.
PMID- 25135808
TI - Management of vernal keratoconjunctivitis.
AB - Vernal keratoconjunctivitis (VKC) is a relatively rare, chronic form of ocular
allergy that can potentially cause severe visual complications. Affecting mainly
children and young adults, it is an IgE- and T cell-mediated disease, leading to
a chronic inflammation in which eosinophil, lymphocyte and structural cell
activation are involved. Treatment of VKC requires a multiple approach that
includes conservative measures and pharmacologic treatment. Patients and parents
should be made aware of the long duration of disease, its chronic evolution and
possible complications. Treatment should be based on the duration and frequency
of symptoms and the severity of corneal involvement. Mast cell stabilizers and
antihistamines have been proven to be effective for the treatment of mild to
moderate forms of VKC. In the most severe cases, topical steroids can be used as
rescue medication to reduce conjunctival and corneal inflammation.
Immunomodulators that have been investigated for VKC treatment include topical
ocular preparations of cyclosporine A and tacrolimus. Topical cyclosporine A has
been proven to be effective in the long-term treatment of VKC, significantly
improving signs and symptoms without significant side effects.
PMID- 25135809
TI - Aflibercept for the treatment of age-related macular degeneration.
AB - Aflibercept is a novel, recombinant, fusion protein that consists of portions of
vascular endothelial growth factor (VEGF) receptor (R) 1 and VEGFR2 extracellular
domains fused to the Fc portion of human immunoglobulin G1. It exhibits higher
affinity for VEGF-A/-B and binds all the VEGF isoforms (VEGF-B and -C, placental
growth factor). The efficacy of aflibercept was assessed in two randomized,
double-masked, multicenter, active-controlled, clinical trials in patients with
choroidal neovascularization due to exudative age-related macular degeneration
(AMD) and compared it's efficacy to ranibizumab, which is already Food and Drug
Administration (FDA)-approved for patients with wet AMD. In the two trials known
as VIEW 1 and VIEW 2, aflibercept was as effective when dosed as 2 mg every 8
weeks after 3 monthly loading doses compared to monthly ranibizumab. Aflibercept
was well tolerated with very rare systemic adverse events, including arterial
thromboembolic events (ATEs). The incidence of ATEs was 1.8% during the first
year of the clinical trials and included non-fatal strokes, non-fatal myocardial
infarction, or death from vascular events or an unknown cause. In November 2011,
aflibercept received FDA approval and is currently used in clinical practice for
patients with wet AMD.
PMID- 25135810
TI - Necrotizing scleritis and peripheral ulcerative keratitis associated with
Wegener's granulomatosis.
AB - INTRODUCTION: To evaluate the complications, efficacy of medical and surgical
treatment, and outcome in patients with necrotizing scleritis and peripheral
ulcerative keratitis associated with Wegener's granulomatosis. METHODS: The
authors reviewed a series of seven patients with Wegener's granulomatosis treated
in the Corneal Department of Zhongshan Ophthalmic Center and the Department of
Ophthalmology of Kashgar First People's Hospital. A detailed chart review was
performed to determine demographic characteristics, ocular presentation, biopsy
and laboratory testing results, treatment, and final outcome. RESULTS: Wegener's
granulomatosis was indicated by ocular and/or systemic findings; biopsy and
immunohistochemistry results supported the diagnosis. Patients with necrotizing
scleritis and/or peripheral ulcerative keratitis received cytotoxic
immunosuppressive therapy; this, in conjunction with surgical treatment, halted
the relentlessly progressive inflammation and preserved the integrity of the
globe in 78% of eyes. Best-Corrected Visual Acuity remained stable in four of
nine eyes, was improved in two of nine eyes, and decreased in three of nine eyes
(secondary to cataract and/or stromal scarring). Although one patient died,
treatment with corticosteroids and cytotoxic agents dramatically improved
outcomes in these patients. CONCLUSION: Necrotizing scleritis and peripheral
ulcerative keratitis often have a poor visual outcome, and may herald an
underlying systemic vasculitis. Wegener's granulomatosis, with the associated
necrotizing scleritis and peripheral ulcerative keratitis, should be managed with
aggressive immunosuppression to avoid the associated morbidity and mortality.
Thus, the ophthalmologist may play a significant role in its early diagnosis and
treatment.
PMID- 25135811
TI - Effect of topical loteprednol on intraocular pressure after selective laser
trabeculoplasty for open-angle glaucoma.
AB - INTRODUCTION: To determine whether there is a statistically significant
difference in the decrease in intraocular pressure (IOP) after selective laser
trabeculoplasty (SLT) between patients receiving a 5-7 days co-administration of
loteprednol versus no loteprednol over the course of 1 year. METHODS: We
conducted a retrospective chart review to evaluate use of loteprednol in patients
aged 30-85 years undergoing SLT for open-angle glaucoma at our center over a 3
year period. RESULTS: Three hundred and eighteen eyes from 313 patients who
underwent a 360 degrees SLT treatment between January 2008 and August 2011 were
included in the analysis. Patients who received loteprednol showed a mean
reduction of 2.5 (+/-SE 0.3) mmHg or 11.8% (+/-1.5%) in IOP versus a mean
reduction of 3.2 (+/-0.6) mmHg or 14.9% (+/-2.5%) in those not treated with
loteprednol. This difference showed a trend toward lower IOP without loteprednol,
but this was not statistically significant (p = 0.29). CONCLUSION: Postoperative
use of loteprednol does not appear to significantly affect IOP in patients
undergoing SLT. A randomized double-blinded study in a larger group of patients
would be required to clarify this issue. Until such information is available, we
recommend that individual clinical judgment be used regarding whether to use
topical steroids in patients undergoing SLT.
PMID- 25135812
TI - Behavior of intraocular pressure after intravitreal injection of triamcinolone
acetonide among egyptians.
AB - PURPOSE: To evaluate the changes in intraocular pressure (IOP) after intravitreal
injection of triamcinolone acetonide for the management of diabetic macular edema
(DME). METHODS: The study design is a prospective, interventional, two-arm, dose
response study. Nineteen patients with bilateral DME were included, one eye for
every patient underwent intravitreal injection of 4 mg triamcinolone acetonide
(group A, 19 eyes), and the other eye of the same patient underwent intravitreal
injection of 8 mg triamcinolone acetonide (group B, 19 eyes); the selection as to
which eye was to receive either dose was random. The patients were followed up
for 6 months after injection; complete ophthalmological examination and optical
coherent topography were done. RESULTS: Intravitreal triamcinolone acetonide was
effective in reduction of DME in group A in the first 3 months only, while in
group B with high dose (8 mg) the improvement continued for 6 months after
injection. Significant IOP rise was observed in both groups with an incidence of
68.1% and 73.7% in groups A and B, respectively. IOP-lowering drugs were used to
control IOP; however, one patient in each group needed glaucoma filtration
surgery in both eyes after intractable glaucoma with failure of medical
treatment. CONCLUSION: Although intravitreal injection of triamcinolone acetonide
is very effective in managing DME and with lower cost than other modalities, the
rise in IOP and the burden of glaucoma are major concerns. High corticosteroid
responder is an individualized reaction irrespective of the intravitreal
triamcinolone acetonide dose used.
PMID- 25135813
TI - Metamemory monitoring and control following retrieval practice for text.
AB - Test-taking is assumed to help learners diagnose what they do and do not know,
and by so doing improve the effectiveness of their subsequent study. Previous
work has examined metamemory monitoring (e.g., predictions of future performance)
and control (e.g., restudy decisions) following testing or retrieval practice
with relatively simple materials (e.g., word pairs). There is reason to believe,
however, that such monitoring and control decisions might be more difficult with
text materials, even after retrieval practice, owing perhaps to difficulty in
accurately assessing one's performance on the retrieval-practice test. In two
experiments, participants read texts about world regions, then engaged in
retrieval practice or rereading of the information in those texts, made estimates
about future performance, and then received an opportunity to restudy the texts
before taking a final recall test, with self-paced restudy enabling an
examination of control processes. Memory predictions were more accurate in the
retrieval-practice than in the rereading condition, and learners in both
conditions allocated restudy time on the basis of their predictions.
Additionally, restudy provided a greater benefit following retrieval practice
than following rereading. The present study has implications for how students can
use retrieval practice with text to foster subsequent learning.
PMID- 25135814
TI - A comparative study of an innate immune response in Lamprologine cichlid fishes.
AB - Social interactions facilitate pathogen transmission and increase virulence.
Therefore, species that live in social groups are predicted to suffer a higher
pathogen burden, to invest more heavily in immune defence against pathogens, or
both. However, there are few empirical tests of whether social species indeed
invest more heavily in immune defence than non-social species. In the current
study, we conducted a phylogenetically controlled comparison of innate immune
response in Lamprologine cichlid fishes. We focused on three species of highly
social cichlids that live in permanent groups and exhibit cooperative breeding
(Julidochromis ornatus, Neolamprologus pulcher and Neolamprologus savoryi) and
three species of non-social cichlids that exhibit neither grouping nor
cooperative behaviour (Telmatochromis temporalis, Neolamprologus tetracanthus and
Neolamprologus modestus). We quantified the innate immune response by injecting
wild fishes with phytohaemagglutinin (PHA), a lectin that causes a cell-mediated
immune response. We predicted that the three highly social species would show a
greater immune reaction to the PHA treatment, indicating higher investment in
immune defence against parasites relative to the three non-social species. We
found significant species-level variation in immune response, but contrary to our
prediction, this variation did not correspond to social system. However, we found
that immune response was correlated with territory size across the six species.
Our results indicate that the common assumption of a positive relationship
between social system and investment in immune function may be overly simplistic.
We suggest that factors such as rates of both in-group and out-group social
interactions are likely to be important mediators of the relationship between
sociality and immune function.
PMID- 25135815
TI - Dual Ambulatory pH Monitoring in Patients with Gastroesophageal Reflux Rendered
Asymptomatic with Proton Pump Inhibitor Therapy.
AB - BACKGROUND: Studies have suggested that proton pump inhibitor (PPI) therapy in
gastroesophageal reflux disease (GERD) achieves high rates of esophageal acid
normalization. AIMS: Our aims were to investigate the adequacy of esophageal and
gastric acid suppression in reflux patients rendered asymptomatic on optimized
PPI therapy. METHODS: We retrospectively analyzed outcomes of dual-sensor,
ambulatory 24-h pH monitoring in referred persistent reflux patients rendered
asymptomatic on PPI therapy. After optimization, we analyzed esophageal and
gastric pH profiles to assess acid suppression and examine differences between
PPIs. In patients with repeat studies, comparisons between different PPI doses
were made. RESULTS: Of 172 asymptomatic GERD patients, 75 (43.6 %) achieved
symptomatic remission with once-daily dosing PPI, and 97 (56.4 %) patients
required twice-daily dosing. Of the entire cohort, 93 (54.1 %) had abnormal and
79 (45.9 %) had normal esophageal pH profiles, with mean percent time pH < 4.0 of
14.3 and 2.4, respectively (p < 0.0001). The percent time esophageal pH was
abnormal did not correlate with the percent time gastric pH was abnormal (p =
0.17). Different PPI formulations demonstrated differences in gastric--not
esophageal--pH times, with esomeprazole exhibiting superior gastric pH
suppression (p < 0.0001). Overall, gastric pH control remained suboptimal, with
pH < 4.0 ranging between 30 and 50 %. Among patients with sequential pH studies,
those with higher PPI dose had improved esophageal pH profiles (p < 0.01).
CONCLUSIONS: In GERD patients rendered asymptomatic on PPI therapy, most continue
to experience abnormal esophageal and gastric acid exposure. The efficacy of acid
suppression therapy, in certain patients, may be much lower than previously
thought.
PMID- 25135816
TI - Microbial associates of the vine mealybug Planococcus ficus (Hemiptera:
Pseudococcidae) under different rearing conditions.
AB - Sap-feeding insects harbor diverse microbial endosymbionts that play important
roles in host ecology and evolution, including contributing to host pest status.
The vine mealybug, Planococcus ficus, is a serious pest of grapevines, vectoring
a number of pathogenic grape viruses. Previous studies have shown that virus
transmission is abolished when mealybugs are raised in the laboratory on potato.
To examine the possible role of microbial symbionts in virus transmission, the
archaeal, bacterial, and fungal microbiota of field and laboratory P. ficus were
characterized using molecular and classical microbiological methods. Lab and
field colonies of P. ficus harbored different microbiota. While both were
dominated by the bacterial obligate nutritional symbionts Moranella and
Tremblaya, field samples also harbored a third bacterium that was allied with
cluster L, a lineage of bacterial symbionts previously identified in aphids.
Archaea were not found in any of the samples. Fungal communities in field
collected mealybugs were dominated by Metschnikowia and Cladosporium species,
while those from laboratory-reared mealybugs were dominated by Alternaria and
Cladosporium species. In conclusion, this study has identified a diverse set of
microbes, most of which appear to be facultatively associated with P. ficus,
depending on environmental conditions. The role of various members of the
mealybug microbiome, as well as how the host plant affects microbial community
structure, remains to be determined.
PMID- 25135817
TI - A combined approach to assess the microbial contamination of the archimedes
palimpsest.
AB - A combined approach, using molecular and microscopic techniques, was used to
identify the microbiota associated with the Archimedes Palimpsest, an unusual
parchment manuscript. SEM analyses revealed the microbial damage to the collagen
fibers and the presence of characteristic cell chains typical of filamentous
bacteria and fungal spores. Molecular analysis confirmed a homogeneous bacterial
community colonizing the manuscript. The phyla Proteobacteria and Actinobacteria
were associated with this ancient parchment; the sequences were most related to
uncultured clones detected in the human skin microbiome and in ephitelium, and to
cultivated species of the genera Acinetobacter and Nocardiopsis. Nevertheless, a
great variation was observed among the different sampled areas indicating fungal
diversity. Blumeria spp. dominated in the healthy areas of the parchment while
degraded areas showed disparate fungal communities, with dominant members of the
genera Mucor and Cladosporium. In addition, the quantification of the beta-actin
gene by real-time PCR analyses (qPCR) revealed a higher fungal abundance on
degraded areas than on the healthy ones.
PMID- 25135819
TI - A Licensed Combined Haemophilus influenzae Type b-Serogroups C and Y
Meningococcal Conjugate Vaccine.
AB - The highest incidence of meningococcal disease occurs in infants younger than 1
year of age. However, in the US, prior to June 2012, there was no meningococcal
vaccine licensed for use in this age group. In the US, where both serogroups C
and Y contribute substantially to the overall epidemiology of invasive
meningococcal disease, a vaccine combining these capsular polysaccharides was
developed. We review the newly licensed HibMenCY-TT (MenHibrixTM, GlaxoSmithKline
Biologicals, Rixensart, Belgium), a novel vaccine containing Haemophilus
influenzae type b (Hib) and serogroups C and Y Neisseria meningitidis conjugated
to tetanus toxoid. We describe the vaccine, summarize the clinical trial data,
and describe the patient populations recommended to receive HibMenCY-TT as their
primary vaccination against Hib. Phase II and III clinical trials found HibMenCY
TT to be well tolerated, safe, and immunogenic when administered at 2, 4, 6, and
12-15 months of age for primary vaccination against both Hib and serogroups C and
Y meningococcal disease. In October 2012, the Advisory Committee on Immunisation
Practice in the US recommended HibMenCY-TT vaccination for infants at increased
risk of meningococcal disease. HibMenCY-TT may be given concomitantly with other
routine infant vaccines. It induces antibodies against Hib as well as
bactericidal activity against meningococcal serogroup C and Y without increasing
the number of injections required. As meningococcal disease epidemiology is
dynamic, global surveillance remains essential. In the future, other countries
may also benefit from the addition of HibMenCY-TT into their vaccine
armamentarium against meningococcal disease.
PMID- 25135820
TI - Cold-adapted proteases as an emerging class of therapeutics.
AB - Proteases have been used in medicine for several decades and are an established
and well tolerated class of therapeutic agent. These proteases were sourced from
mammals or bacteria that exist or have adapted to moderate temperatures
(mesophilic organisms); however, proteases derived from organisms from cold
environments-cold-adapted or psychrophilic proteases-generally have high specific
activity, low substrate affinity, and high catalytic rates at low and moderate
temperatures. Made possible by greater flexibility, psychrophilic enzymes
interact with and transform the substrate at lower energy costs. Cold-adapted
proteases have been used in a wide range of applications, including industrial
functions, textiles, cleaning/hygiene products, molecular biology, environmental
bioremediations, consumer food products, cosmetics, and pharmaceutical
production. In addition to these applications, they have also shown promise as
therapeutic modalities for cosmeceutical applications (by reducing glabellar
[frown] lines) and a number of disease conditions, including bacterial infections
(by disrupting biofilms to prevent bacterial infection), topical wound management
(when used as a debridement agent to remove necrotic tissue and fibrin clots),
oral/dental health management (by removing plaque and preventing periodontal
disease), and in viral infections (by reducing the infectivity of viruses, such
as human rhinovirus 16 and herpes simplex virus). Psychrophilic proteases with
greater activity and stability (than the original organism-derived variant) have
been developed; this coupled with available manufacturing recombinant production
techniques suggests that cold-adapted proteases have a promising future as a
distinct therapeutic class with diverse clinical applications.
PMID- 25135818
TI - Surgical patients travel longer distances than non-surgical patients to receive
care at a rural hospital in Mozambique.
AB - BACKGROUND: Surgical care is increasingly recognised as an important component of
global health delivery. However, there are still major gaps in knowledge related
to access to surgical care in low-income countries. In this study, we compare
distances travelled by surgical patients with patients seeking other medical
services at a first-level hospital in rural Mozambique. METHODS: Data were
collected on all inpatients at Hospital Rural de Chokwe in rural Mozambique
between 20 June 2012 and 3 August 2012. Euclidean distances travelled by surgical
versus non-surgical patients using coordinates of each patient's city of
residence were compared. Data were analysed using ArcGIS 10 and STATA. RESULTS:
In total, 500 patients were included. Almost one-half (47.6%) lived in the city
where the hospital is based. By hospital ward, the majority (62.0%) of maternity
patients came from within the hospital's city compared with only 35.2% of
surgical patients. The average distance travelled was longest for surgical
patients (42 km) compared with an average of 17 km for patients on all other
wards. CONCLUSIONS: Patients seeking surgical care at this first-level hospital
travel farther than patients seeking other services. While other patients may
have access to at community clinics, surgical patients depend more heavily on the
services available at first-level hospitals.
PMID- 25135821
TI - Low specificity of a malaria rapid diagnostic test during an integrated community
case management trial.
AB - INTRODUCTION: Parasitological confirmation before administration of antimalarial
treatment has been recommended by the World Health Organization in everyone
presenting with symptoms suggestive of malaria at all levels of the health
system. METHODS: The authors assessed the performance of a histidine-rich protein
2-based malaria rapid diagnostic test used by community health workers in the
context of an integrated approach to diagnosis and treatment for malaria and
pneumonia. A total of 525 children below 5 years of age were recruited into the
study. Children with fever/history of fever within the last 24 h were tested with
the rapid diagnostic test (RDT) and a blood smear was obtained for delayed
reading. RESULTS: Overall, the FirstSignTM Malaria Pf (Unimed International Inc,
South San Francisco, USA) has shown a high sensitivity profile of 97.9% (95% CI
96.3-98.8), but a low specificity of 53.4% (95% CI 49.1-57.7). The specificity
was significantly lower during the high transmission season at 25.4% (95% CI 20.5
31.0) compared to 63.7% (95% CI 57.6-69.4%) at the low transmission season. The
negative predictive value (NPV) was 95.4% (95% CI 93.2-96.9) and positive
predictive value was 71.7% (95% CI 67.7-75.4). The NPV was significantly higher
during the low transmission season at 98.2% (95% CI 95.7-99.3) than compared to
80.0% (95% CI 74.7-84.4) at the high transmission season. CONCLUSION: With such a
low specificity, caution should be exercised when using these RDTs for community
case management of malaria.
PMID- 25135822
TI - Incidence and predisposing factors of vancomycin-induced nephrotoxicity in
children.
AB - INTRODUCTION: To investigate the pattern of vancomycin-associated nephrotoxicity
in children and to examine potential predisposing factors for nephrotoxicity,
including average serum trough concentrations >=10 MUg/mL. METHODS: Patients >=1
week old to <=15 years with normal baseline serum creatinine values who received
vancomycin for >=48 h between October 2010 and September 2012 were
retrospectively evaluated. Nephrotoxicity was defined as a serum creatinine
increase of >=0.5 mg/dL or >=50% baseline increase over 2 days. Patients with
average serum trough concentrations >=10 MUg/mL were compared with a lower trough
group. RESULTS: Renal toxicity occurred in 72 (27.2%) of the 265 studied
pediatric cases. High trough vancomycin levels >=10 MUg/mL were presented in 59
pediatric patients suffering from nephrotoxicity. Using multiple regression
analysis, cases admitted to the intensive care unit (ICU) and to whom
aminoglycoside medication was administered concurrently with vancomycin
medication showed a significant high renal toxicity incidence [odds ratio (OR)
2.91; 95% confidence interval (CI) 1.70, 8.61; P value <0.03)] and (OR 9.11; 95%
CI 4.11, 24.13; P < 0.05), respectively. CONCLUSION: Renal function tests and
continuous monitoring of vancomycin trough levels for children receiving
vancomycin therapy, especially admitted to the ICU and given other aminoglycoside
medications, are essential.
PMID- 25135823
TI - Treatment of Asymptomatic Carriers of Plasmodium falciparum with Artemether
Lumefantrine: Impact on the Prevalence of Anemia.
AB - INTRODUCTION: An investigation of whether treatment of asymptomatic carriers of
Plasmodium falciparum with artemether-lumefantrine (AL), in addition to the
routine treatment of symptomatic cases with AL, could improve the prevalence of
anemia in 18 villages in Burkina Faso. METHODS: This was a single-center,
controlled, parallel, cluster-randomized study to evaluate the effect of
systematic treatment of P. falciparum asymptomatic carriers at a community level
on hemoglobin (Hb) levels and anemic status of children (<5 years) and adults
during four screening campaigns carried out over a 12-month period, compared with
no treatment of asymptomatic carriers. RESULTS: The change in Hb level in all
asymptomatic carriers aged >6 months from Day 1 to Day 28 of the first campaign
was +0.53 g/dl (from 11.81 to 12.33 g/dl) in the intervention arm vs. -0.21 g/dl
(from 12.06 to 11.86 g/dl) in the control arm (P < 0.001). During the same
period, the proportion of asymptomatic carriers aged >6 months to <5 years with
anemia in the intervention arm decreased by 31.1% (from 75.7% to 44.6%), compared
with a decrease of 4.7% (from 76.3% to 71.6%) in the control arm. Over 12 months,
the proportion of asymptomatic carriers with anemia (mild, moderate, or severe)
was reduced in both arms. CONCLUSION: Systematic screening and treatment of
asymptomatic carriers of P. falciparum with AL at the community level can reduce
the prevalence of anemia in children in the short term (28 days), although the
effect was not maintained at 12 months.
PMID- 25135824
TI - Psoriasis, anti-tumor necrosis factor therapy, and tuberculosis: report of three
challenging cases and literature review.
AB - INTRODUCTION: The era of biologic therapies has provided new options for the
treatment of chronic plaque psoriasis. However, safety concerns have led to
intensive screening and monitoring of patients receiving anti-tumor necrosis
factor alpha (anti-TNF-alpha) agents. METHODS: The authors describe the cases of
three patients with moderate to severe psoriasis treated with anti-TNF agents,
with challenging diagnostic and treatment aspects regarding tuberculosis (TB)
infection, a serious adverse event associated with this type of treatment. The
cases are discussed in the context of a comprehensive literature review
describing the risk of TB associated with the use of TNF inhibitors. A critical
review of the clinical trials that have tested the safety of these agents is also
presented. RESULTS: One patient, who tested negatively for latent TB infection
(LTBI) during screening, developed active TB under adalimumab therapy. For two
other patients the diagnosis and management of LTBI in relation to anti-TNF
therapy represented a challenge. Although clinical trials involving the use of
anti-TNF therapy for psoriasis haven't demonstrated a high TB incidence, active
TB is continuously reported in association with this treatment. CONCLUSIONS:
Findings from clinical practice and the scientific literature indicate that anti
TNF therapies are associated with an increased risk of TB, and close monitoring
of patients is needed.
PMID- 25135826
TI - A systematic review and meta-analysis on the role of varicosity treatment in the
context of truncal vein ablation.
AB - BACKGROUND: With the advent of endovenous truncal ablation under local
anaesthetic for the treatment of varicose veins, the fate of varicosed
tributaries has become controversial, with centres offering different timings of
treatment, if offered at all. This study aims to review the literature assessing
delayed and simultaneous varicosity treatment during truncal ablation. METHODS:
Randomised trials and cohort studies concerning varicosity treatment timing were
identified through a systematic literature search. Requirements for further
treatment, quality of life and rate of venous thrombotic events were assessed for
meta-analysis. RESULTS: Four studies were identified assessing need for further
varicosity procedure, with no significant difference seen between simultaneous or
delayed treatment (p = 0.339). Two studies assessed quality of life, with
simultaneous treatment providing significantly improved outcomes at six weeks (p
= 0.029) but not at 12 weeks (p = 0.283). Studies examining venous thrombotic
events showed no difference in venous thromboembolism rate between simultaneous
or delayed treatment approaches (p = 0.078). CONCLUSION: The evidence base
regarding timing of varicosity treatment is sparse; however, it does show that
simultaneous treatment of varicosities leads to early gains in quality of life,
with a non-significant trend for fewer further procedures but more venous
thrombotic events.
PMID- 25135825
TI - Postoperative pyoderma gangrenosum in association with renal cell carcinoma and
chronic lymphocytic leukemia.
AB - INTRODUCTION: Pyoderma gangrenosum (PG) is a rare sterile neutrophilic dermatosis
characterized by painful recurrent ulcerations. It is frequently associated with
inflammatory bowel disease, rheumatoid arthritis, or malignancies. PG is a
diagnosis of exclusion, and it is based on clinical presentation, histology,
history of an underlying disease, and exclusion of other causes of ulceration.
CASE REPORT: The authors report a 62-year-old male who developed a nonhealing
ulcer at the site of incision following nephrectomy for renal cell carcinoma.
Past medical history included chronic lymphocytic leukemia treated with
rituximab. Histology of the skin lesion showed a phlegmonous nonspecific
inflammation without being able to differentiate between a necrotizing wound
infection and PG. The patient's condition was initially diagnosed as an
infectious process and treated accordingly. After unsuccessful results with
systemic antibiotics, high-dose corticosteroids induced prompt healing of the
wound. On these bases, the diagnosis of postoperative PG within chronic
lymphocytic leukemia and renal cell carcinoma was made. CONCLUSION: Faced with
postoperative necrotizing ulceration resistant to correctly administered
antibiotics, PG must be considered. In such condition, the diagnosis must not be
guided primarily by histology and early advice of a dermatologist is recommended.
PMID- 25135827
TI - Needle track tumor seeding after radiofrequency ablation of a thyroid tumor.
AB - A 19-year-old female underwent two radiofrequency ablation procedures for a
thyroid tumor that was proven to be nodular hyperplasia versus a follicular
neoplasm by fine-needle aspiration. Two years after the last follow-up, the
thyroid mass had grown and a newly developed mass was detected in the platysma
muscle. After surgery, the thyroid mass was revealed to be a solid papillary
thyroid carcinoma, and the subplatysmal mass was tumor seeding.
PMID- 25135828
TI - CD1d(hi)CD5+ B cells expanded by GM-CSF in vivo suppress experimental autoimmune
myasthenia gravis.
AB - IL-10-competent subset within CD1d(hi)CD5(+) B cells, also known as B10 cells,
has been shown to regulate autoimmune diseases. Whether B10 cells can prevent or
suppress the development of experimental autoimmune myasthenia gravis (EAMG) has
not been studied. In this study, we investigated whether low-dose GM-CSF, which
suppresses EAMG, can expand B10 cells in vivo, and whether adoptive transfer of
CD1d(hi)CD5(+) B cells would prevent or suppress EAMG. We found that treatment of
EAMG mice with low-dose GM-CSF increased the proportion of CD1d(hi)CD5(+) B cells
and B10 cells. In vitro coculture studies revealed that CD1d(hi)CD5(+) B cells
altered T cell cytokine profile but did not directly inhibit T cell
proliferation. In contrast, CD1d(hi)CD5(+) B cells inhibited B cell proliferation
and its autoantibody production in an IL-10-dependent manner. Adoptive transfer
of CD1d(hi)CD5(+) B cells to mice could prevent disease, as well as suppress EAMG
after disease onset. This was associated with downregulation of mature dendritic
cell markers and expansion of regulatory T cells resulting in the suppression of
acetylcholine receptor-specific T cell and B cell responses. Thus, our data have
provided significant insight into the mechanisms underlying the tolerogenic
effects of B10 cells in EAMG. These observations suggest that in vivo or in vitro
expansion of CD1d(hi)CD5(+) B cells or B10 cells may represent an effective
strategy in the treatment of human myasthenia gravis.
PMID- 25135829
TI - Single-cell analysis of innate cytokine responses to pattern recognition receptor
stimulation in children across four continents.
AB - Innate immunity instructs adaptive immunity, and suppression of innate immunity
is associated with an increased risk for infection. We showed previously that
whole-blood cellular components from a cohort of South African children secreted
significantly lower levels of most cytokines following stimulation of pattern
recognition receptors compared with whole blood from cohorts of Ecuadorian,
Belgian, or Canadian children. To begin dissecting the responsible molecular
mechanisms, we set out to identify the relevant cellular source of these
differences. Across the four cohorts represented in our study, we identified
significant variation in the cellular composition of whole blood; however, a
significant reduction in the intracellular cytokine production on the single-cell
level was only detected in South African children's monocytes, conventional
dendritic cells, and plasmacytoid dendritic cells. We also uncovered a marked
reduction in polyfunctionality for each of these cellular compartments in South
African children compared with children from the other continents. Together, our
data identify differences in cell composition, as well as profoundly lower
functional responses of innate cells, in our cohort of South African children. A
possible link between altered innate immunity and increased risk for infection or
lower response to vaccines in South African infants needs to be explored.
PMID- 25135830
TI - Identification of a novel neutrophil population: proangiogenic granulocytes in
second-trimester human decidua.
AB - The maternal leukocytes of the first-trimester decidua play a fundamental role in
implantation and early development of the fetus and placenta, yet little is known
regarding the second-trimester decidual environment. Our multicolor flow
cytometric analyses of human decidual leukocytes detected an elevation in tissue
resident neutrophils in the second trimester. These cells in both human and
murine samples were spatially restricted to decidua basalis. In comparison with
peripheral blood neutrophils (PMNs), the decidual neutrophils expressed high
levels of neutrophil activation markers and the angiogenesis-related proteins:
vascular endothelial growth factor-A, Arginase-1, and CCL2, similarly shown in
tumor-associated neutrophils. Functional in vitro assays showed that second
trimester human decidua conditioned medium stimulated transendothelial PMN
invasion, upregulated VEGFA, ARG1, CCL2, and ICAM1 mRNA levels, and increased PMN
driven in vitro angiogenesis in a CXCL8-dependent manner. This study identified a
novel neutrophil population with a physiological, angiogenic role in human
decidua.
PMID- 25135831
TI - Pregnancy and malaria exposure are associated with changes in the B cell pool and
in plasma eotaxin levels.
AB - Pregnancy triggers immunological changes aimed to tolerate the fetus, but its
impact on B lymphocytes is poorly understood. In addition, exposure to the
Plasmodium parasite is associated with altered distribution of peripheral memory
B cell (MBC) subsets. To study the combined impact of high malaria exposure and
pregnancy in B cell subpopulations, we analyzed PBMCs from pregnant and
nonpregnant individuals from a malaria-nonendemic country (Spain) and from a high
malaria-endemic country (Papua New Guinea). In the malaria-naive cohorts,
pregnancy was associated with a significant expansion of all switched (IgD(-))
MBC and a decrease of naive B cells. Malaria-exposed women had more atypical MBC
and fewer marginal zone-like MBC, and their levels correlated with both
Plasmodium vivax- and Plasmodium falciparum-specific plasma IgG levels. Classical
but not atypical MBC were increased in P. falciparum infections. Moreover, active
atypical MBC positively correlated with proinflammatory cytokine plasma
concentrations and had lower surface IgG levels than the average. Decreased
plasma eotaxin (CCL11) levels were associated with pregnancy and malaria exposure
and also correlated with B cell subset frequencies. Additionally, active atypical
and active classical MBC expressed higher levels of eotaxin receptor CCR3 than
the other B cell subsets, suggesting a chemotactic effect of eotaxin on these B
cell subsets. These findings are important to understand immunity to infections
like malaria that result in negative outcomes for both the mother and the newborn
and may have important implications on vaccine development.
PMID- 25135832
TI - Live simian immunodeficiency virus vaccine correlate of protection: local
antibody production and concentration on the path of virus entry.
AB - We sought design principles for a vaccine to prevent HIV transmission to women by
identifying correlates of protection conferred by a highly effective live
attenuated SIV vaccine in the rhesus macaque animal model. We show that
SIVmac239Deltanef vaccination recruits plasma cells and induces ectopic lymphoid
follicle formation beneath the mucosal epithelium in the rhesus macaque female
reproductive tract. The plasma cells and ectopic follicles produce IgG Abs
reactive with viral envelope glycoprotein gp41 trimers, and these Abs are
concentrated on the path of virus entry by the neonatal FcR in cervical reserve
epithelium and in vaginal epithelium. This local Ab production and delivery
system correlated spatially and temporally with the maturation of local
protection against high-dose pathogenic SIV vaginal challenge. Thus, designing
vaccines to elicit production and concentration of Abs at mucosal frontlines
could aid in the development of an effective vaccine to protect women against HIV
1.
PMID- 25135834
TI - Bispecificity for myelin and neuronal self-antigens is a common feature of CD4 T
cells in C57BL/6 mice.
AB - The recognition of multiple ligands by a single TCR is an intrinsic feature of T
cell biology, with important consequences for physiological and pathological
processes. Polyspecific T cells targeting distinct self-antigens have been
identified in healthy individuals as well as in the context of autoimmunity. We
have previously shown that the 2D2 TCR recognizes the myelin oligodendrocyte
glycoprotein epitope (MOG)35-55 as well as an epitope within the axonal protein
neurofilament medium (NF-M15-35) in H-2(b) mice. In this study, we assess whether
this cross-reactivity is a common feature of the MOG35-55-specific T cell
response. To this end, we analyzed the CD4 T cell response of MOG35-55-immunized
C57BL/6 mice for cross-reactivity with NF-M15-35. Using Ag recall responses, we
established that an important proportion of MOG35-55-specific CD4 T cells also
responded to NF-M15-35 in all mice tested. To study the clonality of this
response, we analyzed 22 MOG35-55-specific T cell hybridomas expressing distinct
TCR. Seven hybridomas were found to cross-react with NF-M15-35. Using an alanine
scan of NF-M18-30 and an in silico predictive model, we dissected the molecular
basis of cross-reactivity between MOG35-55 and NF-M15-35. We established that NF
M F24, R26, and V27 proved important TCR contacts. Strikingly, the identified TCR
contacts are conserved within MOG38-50. Our data indicate that due to linear
sequence homology, part of the MOG35-55-specific T cell repertoire of all C57BL/6
mice also recognizes NF-M15-35, with potential implications for CNS autoimmunity.
PMID- 25135833
TI - SARS-coronavirus open reading frame-9b suppresses innate immunity by targeting
mitochondria and the MAVS/TRAF3/TRAF6 signalosome.
AB - Coronaviruses (CoV) have recently emerged as potentially serious pathogens that
can cause significant human morbidity and death. The severe acute respiratory
syndrome (SARS)-CoV was identified as the etiologic agent of the 2002-2003
international SARS outbreak. Yet, how SARS evades innate immune responses to
cause human disease remains poorly understood. In this study, we show that a
protein encoded by SARS-CoV designated as open reading frame-9b (ORF-9b)
localizes to mitochondria and causes mitochondrial elongation by triggering
ubiquitination and proteasomal degradation of dynamin-like protein 1, a host
protein involved in mitochondrial fission. Also, acting on mitochondria, ORF-9b
targets the mitochondrial-associated adaptor molecule MAVS signalosome by
usurping PCBP2 and the HECT domain E3 ligase AIP4 to trigger the degradation of
MAVS, TRAF3, and TRAF 6. This severely limits host cell IFN responses. Reducing
either PCBP2 or AIP4 expression substantially reversed the ORF-9b-mediated
reduction of MAVS and the suppression of antiviral transcriptional responses.
Finally, transient ORF-9b expression led to a strong induction of autophagy in
cells. The induction of autophagy depended upon ATG5, a critical autophagy
regulator, but the inhibition of MAVS signaling did not. These results indicate
that SARS-CoV ORF-9b manipulates host cell mitochondria and mitochondrial
function to help evade host innate immunity. This study has uncovered an
important clue to the pathogenesis of SARS-CoV infection and illustrates the
havoc that a small ORF can cause in cells.
PMID- 25135835
TI - Composition and occurrence of lipid droplets in the cyanobacterium Nostoc
punctiforme.
AB - Inclusions of neutral lipids termed lipid droplets (LDs) located throughout the
cell were identified in the cyanobacterium Nostoc punctiforme by staining with
lipophylic fluorescent dyes. LDs increased in number upon entry into stationary
phase and addition of exogenous fructose indicating a role for carbon storage,
whereas high-light stress did not increase LD numbers. LD accumulation increased
when nitrate was used as the nitrogen source during exponential growth as
compared to added ammonia or nitrogen-fixing conditions. Analysis of isolated LDs
revealed enrichment of triacylglycerol (TAG), alpha-tocopherol, and C17 alkanes.
LD TAG from exponential phase growth contained mainly saturated C16 and C18 fatty
acids, whereas stationary phase LD TAG had additional unsaturated fatty acids
characteristic of whole cells. This is the first characterization of
cyanobacterial LD composition and conditions leading to their production. Based
upon their abnormally large size and atypical location, these structures
represent a novel sub-organelle in cyanobacteria.
PMID- 25135836
TI - Repeat analysis and incurred sample reanalysis: recommendation for best practices
and harmonization from the global bioanalysis consortium harmonization team.
AB - The A7 harmonization team (A7 HT), a part of the Global Bioanalysis Consortium
(GBC), focused on reviewing best practices for repeat analysis and incurred
sample reanalysis (ISR) as applied during regulated bioanalysis. With
international representation from Europe, Latin America, North America, and the
Asia Pacific region, the team first collated common practices and guidance
recommendations and assessed their suitability from both a scientific and
logistical perspective. Subsequently, team members developed best practice
recommendations and refined them through discussions and presentations with
industry experts at scientific meetings. This review summarizes the team findings
and best practice recommendations. The few topics where no consensus could be
reached are also discussed. The A7 HT recommendations, together with those from
the other GBC teams, provide the basis for future international harmonization of
regulated bioanalytical practices.
PMID- 25135837
TI - Population pharmacokinetic/pharmacodynamic modeling of guanfacine effects on QTc
and heart rate in pediatric patients.
AB - Using a previously developed population pharmacokinetic model, an exposure
response (ER) model was successfully developed to describe guanfacine plasma
concentrations and changes in heart rate (HR) and the QT interval. Guanfacine
exposure was associated with small decreases in HR and a small prolongation of
the population-corrected QT (QTcP) interval. Based on the final ER model for
effect of guanfacine on HR, the estimated population typical decrease in HR would
be 2.3% (2.1-2.7%) of the baseline circadian HR for every 1 ng/mL of guanfacine
exposure. A QTcP was developed for the analysis using the sampled population. An
effect of sex on baseline-corrected QT (BQTP) was the only covariate effect in
the final ER model for QTcP, its inclusion resulting in a typical baseline QTcP
estimate that is 9 (5-13) ms higher for females. There was no evidence of QT-RR
hysteresis. A linear model was used to relate guanfacine plasma concentrations to
QTcP. The typical (95% confidence interval) slope parameter was estimated to be
0.941 (0.62-1.25) ms/ng/mL. The final model predicted an approximate 1-ms
increase from baseline for every 1 ng/mL of guanfacine in plasma. The main
predictor of QTcP prolongation was guanfacine exposure, which decreased with body
weight and increased with dose.
PMID- 25135838
TI - Organ transplantation from donors (cadaveric or living) with a history of
malignancy: review of the literature.
AB - The evolution of organ transplantation has resulted in extended lifespan as well
as better life quality of patients with end-stage diseases, which in turn causes
an increased demand for organs. The persistent organ shortage requires a careful
reconsideration of potential donors (living or cadaveric) that have current or
historical malignancies. Donors with low-grade skin tumors, carcinomas in situ of
the uterine cervix, and primary central nervous system (CNS) tumors can be
considered as potential donors for recipients dying on wait list longing for
organ transplantation. Recently, transplant centers have turned to other types of
malignancies including low grade renal cell carcinoma, prostate, ureteral,
endometrial and breast cancer, and favorable outcomes have been shown in such
innovations. When considering donors with a history of malignancy, general
biologic behavior of the tumor type, histology and stage at the time of
diagnosis, and the length of disease-free interval should be considered
(Transplantation 2002;74(12):1657-1663). With the review of literatures, we
illustrate the organ utilization from donors with malignancies all around the
world since earlier times and give some suggestions for decision making under the
circumstance of whether to choose those marginal donors or not on the basis of
reviewed literatures.
PMID- 25135839
TI - The Spanish version of the Body Image Scale (S-BIS): psychometric properties in a
sample of breast and gynaecological cancer patients.
AB - PURPOSE: The aim of this study is to develop a Spanish version of the Body Image
Scale (Hopwood et al. Eur J Cancer 37(2):189-197, 2001) and to analyze its
psychometric properties in a sample of women with breast or gynaecological
cancer. METHODS: The Spanish version of the Body Image Scale was developed using
a forward and backward translation technique. A total sample of 100 women who had
undergone radical surgery for breast (n = 50) or gynaecological cancer (n = 50)
completed the scale. RESULTS: Factor analysis resulted in a single-factor
solution, both in the total sample and in the two subgroups, accounting for >76 %
variance. Internal consistency (Cronbach's alpha) was 0.960. The Spanish version
of the Body Image Scale correlated negatively with self-esteem (r = -0.733),
quality of life (r = -0.632) and age (r = -0.643) and positively with depression
(r = 0.832) and anxiety (r = 0.564); all p values < 0.01. CONCLUSIONS: To our
knowledge, this is the first study that provides a Spanish version of the Body
Image Scale. Our results show a stable factorial structure between samples with a
single-factor solution and good psychometric properties, suggesting that it is a
suitable tool for measuring body image concerns among Spanish-speaking cancer
patients. Its brevity and comprehensibility allow a quick assessment both in
clinical and research settings.
PMID- 25135841
TI - The basolateral amygdala is necessary for negative prediction errors to enhance
cue salience, but not to produce conditioned inhibition.
AB - Behavioral evidence shows that prediction errors (PEs) not only drive associative
learning, but also enhance the salience of predictive cues, making them better
able to capture attention when they are next encountered. Research from our
laboratory suggests that this latter consequence of PEs depends on a neural
circuit that includes the amygdala. Lesions of the basolateral complex of the
amygdala (BLA), for instance, selectively disrupt enhancements in cue processing
that are normally induced by positive PEs without compromising simple excitatory
learning. This result is consistent with electrophysiological evidence showing
that BLA neurons track positive PEs. Interestingly, the same neurons also seem to
track negative PEs, suggesting the possibility that the BLA might also use these
errors to drive enhancements in cue processing. Here, we examined the role of the
BLA in the processing (Experiment 1) and utilization (Experiment 2) of negative
PEs in increasing cue salience in an unblocking procedure. Using FOS expression
as an index of neural activity, Experiment 1 confirmed that BLA neurons track
negative PEs with reinforcement downshifts. This tracking was evident both when
these errors were generated by decreasing the concentration of a sucrose
reinforcer (which encourages the development of conditioned inhibition) and when
they were generated by decreasing the number of sucrose reinforcers (which
encourages excitatory learning - unblocking - and allows the detection of
enhancements in cue processing). Experiment 2 demonstrated that BLA lesions
abolished enhancements in cue processing while sparing inhibitory learning. These
results suggest a general role of the BLA in utilizing PEs, whatever their sign,
for boosting cue processing.
PMID- 25135840
TI - Glioblastoma multiforme from diagnosis to death: a prospective, hospital-based,
cohort, pilot feasibility study of patient reported symptoms and needs.
AB - PURPOSE: Glioblastoma (GBM) patients have many palliative care (PC) issues. To
date, there are no studies examining the prospective usage of validated PC
assessment tools as patient reported outcome measures for GBM patients. METHODS:
GBM patients' PC issues were assessed from diagnosis to death or for at least 12
months every 7 weeks (+/-8 days) using semi-structured interviews and the Hospice
and Palliative Care Evaluation (HOPE, including Eastern Cooperative Oncology
Group (ECOG) performance status, 17 items) and the Palliative Outcome Scale (POS,
11 items). Data from patients who died within 12 months of the last patient's
enrollment were evaluated using summarizing content analysis, visual graphical
analysis (VGA), and linear mixed models for repeated measures. RESULTS: Nineteen
of 33 patients screened were enrolled; two dropped out and four were still alive
at the end of the study. The remaining 13 were assessed at 59 points until death
(time range 4-68 weeks; 1-10 contacts per patient; assessment: self, 33; joint,
8; external, 18). VGA of the HOPE and POS data, including all 1,652 assessed item
data, showed consistent trajectory profiles for 14 of 28 items: 10 were
increasing (meaning symptom worsening) and comprised predominantly psychosocial
issues and care dependency. Type of assessment partly interacted with time,
however, not qualitatively so. Analysis of semi-structured interviews revealed
delayed interactions with PC/hospice services and numerous neuropsychiatric
problems not detected by HOPE and POS. CONCLUSIONS: Prospective self-assessment
of GBM patients' PC issues is feasible. However, disease progression may
necessitate further, external assessment. Modification of existing PC assessment
tools is needed to detect GBM-specific issues.
PMID- 25135843
TI - Randall Dudley Bloomfield, MD: physician and advocate for disadvantaged
communities.
PMID- 25135842
TI - Strategies for hepatitis C testing and linkage to care for vulnerable
populations: point-of-care and standard HCV testing in a mobile medical clinic.
AB - Despite new Hepatitis C virus (HCV) therapeutic advances, challenges remain for
HCV testing and linking patients to care. A point-of-care (POC) HCV antibody
testing strategy was compared to traditional serological testing to determine
patient preferences for type of testing and linkage to treatment in an innovative
mobile medical clinic (MMC). From 2012 to 2013, all 1,345 MMC clients in New
Haven, CT underwent a routine health assessment, including for HCV. Based on
patient preferences, clients could select between standard phlebotomy or POC HCV
testing, with results available in approximately 1 week versus 20 min,
respectively. Outcomes included: (1) accepting HCV testing; (2) preference for
rapid POC HCV testing; and (3) linkage to HCV care. All clients with reactive
test results were referred to a HCV specialty clinic. Among the 438 (32.6 %)
clients accepting HCV testing, HCV prevalence was 6.2 % (N = 27), and 209 (47.7
%) preferred POC testing. Significant correlates of accepting HCV testing was
lower for the "baby boomer" generation (AOR 0.67; 95 % CI 0.46-0.97) and white
race (AOR 0.55; 95 % CI 0.36-0.78) and higher for having had a prior STI
diagnosis (AOR 5.03; 95 % CI 1.76-14.26), prior injection drug use (AOR 2.21; 95
% CI 1.12-4.46), and being US-born (AOR 1.76; 95 % CI 1.25-2.46). Those diagnosed
with HCV and preferring POC testing (N = 16) were significantly more likely than
those choosing standard testing (N = 11) to be linked to HCV care within 30 days
(93.8 vs. 18.2 %; p < 0.0001). HCV testing is feasible in MMCs. While patients
equally preferred POC and standard HCV testing strategies, HCV-infected patients
choosing POC testing were significantly more likely to be linked to HCV
treatment. Important differences in risk and background were associated with type
of HCV testing strategy selected. HCV testing strategies should be balanced based
on costs, convenience, and ability to link to HCV treatment.
PMID- 25135844
TI - Mortality from internal and external radiation exposure in a cohort of male
German uranium millers, 1946-2008.
AB - PURPOSE: To examine exposure-response relationships between ionizing radiation
and several mortality outcomes in a subgroup of 4,054 men of the German uranium
miner cohort study, who worked between 1946 and 1989 in milling facilities, but
never underground or in open pit mines. METHODS: Mortality follow-up was from
1946 to 2008, accumulating 158,383 person-years at risk. Cumulative exposure to
radon progeny in working level months (WLM) (mean = 8, max = 127), long-lived
radionuclides from uranium ore dust in kBqh/m(3) (mean = 3.9, max = 132),
external gamma radiation in mSv (mean = 26, max = 667) and silica dust was
estimated by a comprehensive job-exposure matrix. Internal Poisson regression
models were applied to estimate the linear excess relative risk (ERR) per unit of
cumulative exposure. RESULTS: Overall, a total of 457, 717 and 111 deaths
occurred from malignant cancer, cardiovascular diseases and non-malignant
respiratory diseases, respectively. Uranium ore dust and silica dust were not
associated with mortality from any of these disease groups. A statistically
significant relationship between cumulative radon exposure and mortality from all
cancers (ERR/100 WLM = 1.71; p = 0.02), primarily due to lung cancer (n = 159;
ERR/100 WLM = 3.39; p = 0.05), was found. With respect to cumulative external
gamma radiation, an excess of mortality of solid cancers (n = 434; ERR/Sv = 1.86;
p = 0.06), primarily due to stomach cancer (n = 49, ERR/Sv = 10.0; p = 0.12), was
present. CONCLUSION: The present findings show an excess mortality from lung
cancer due to radon exposure and from solid cancers due to external gamma
radiation in uranium millers that was not statistically significant. Exposure to
uranium was not associated with any cause of death, but absorbed organ doses were
estimated to be low.
PMID- 25135845
TI - Impact of desmopressin on nocturia due to nocturnal polyuria in men with lower
urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH).
AB - PURPOSE: To evaluate the efficacy of desmopressin on nocturia, quality of sleep
(QoS), and health-related quality of life (HRQoL) in men with lower urinary tract
symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) and nocturia due
to nocturnal polyuria (NP) as the predominant symptom. METHODS: A German
observational, multicenter, post-marketing surveillance study including men with
LUTS/BPH and nocturia due to NP starting 3 months of desmopressin treatment.
RESULTS: In total, 137 patients with a mean of 3.8 nocturnal voids (range 2-7)
were included. Desmopressin significantly reduced the mean number of nocturnal
voids by 53 %, mean IPSS nocturia question by 50 %, and the mean ratio of
night/24-h urine volume by 39 % from baseline to endpoint. The hours of
undisturbed sleep significantly increased by 74 %; 71 % of men reported about
undisturbed sleep of >=4 h at study end. Additionally, there was a significant
reduction in the Leeds Sleep Evaluation Questionnaire score, indicating a
clinically relevant QoS improvement. This was associated with an improved HRQoL,
as shown by a significant improvement in both the mean IPSS-QoL question by 43 %
and mean ICIQ-N nocturia problem question by 53 %. Concomitant alpha-blocker use
had no effect on the efficacy of desmopressin. The incidence of adverse events
was low (2.2 %). Hyponatremia was not observed in any patient. The majority of
patients and physicians rated the efficacy and tolerability of desmopressin as
good/very good. CONCLUSIONS: Desmopressin is an effective and well-tolerated
treatment for nocturia due to NP in patients with LUTS/BPH in daily practice
under routine conditions.
PMID- 25135847
TI - Race/ethnicity and disparities in mastectomy practice in the Breast Cancer Care
in Chicago study.
AB - PURPOSE: To examine racial/ethnic disparities in mastectomy practice and explore
mediating factors to explain the disparity. METHODS: Participants included 989
females aged 30-79 years, from a population-based study of newly diagnosed
(primary in situ/invasive) breast cancer patients, in Chicago, Illinois, from
2005 to 2008, who completed an interview. Medical records were also abstracted
for tumor, diagnostic, and treatment information. Multivariable logistic
regression models with model-based standardization were used to estimate risk
differences. Differences in rescaled coefficients were used to estimate the
proportion of the disparity that could be mediated by patient and tumor
characteristics. RESULTS: Mastectomy prevalence overall was 40 %. Factors
significantly associated with increased rates of mastectomy (p < 0.05) included
the following: non-Hispanic (nH) black and Hispanic race/ethnicity; younger age
at diagnosis; lower socioeconomic status (SES); lack of recency of and adherence
to screening mammography; and higher tumor pathologic stage and grade. In
adjusted models (age, body mass index, comorbidity), compared to nH white
patients, mastectomy was increased by 10 % points in both nH black (95 %
confidence interval [CI] 0.03, 0.18; p = 0.007) and Hispanic (95 % CI 0.01, 0.19;
p = 0.028) patients. After accounting for the proportion of disparity mediated by
tumor stage, the disparity was reduced by about a third in nH black (risk
difference = 0.07, 95 % CI -0.01, 0.14) and half in Hispanic patients (risk
difference = 0.04, 95 % CI -0.05, 0.13). Additional control for mediation by SES
and other tumor-related factors almost completely eliminated the nH black:nH
white disparity. CONCLUSIONS: The best approach to reducing the racial/ethnic
disparity in mastectomy rates would be to intervene on factors that could affect
stage at diagnosis.
PMID- 25135846
TI - Evolution of a strategy for preparing bioactive small molecules by sequential
multicomponent assembly processes, cyclizations, and diversification.
AB - A strategy for generating diverse collections of small molecules has been
developed that features a multicomponent assembly process (MCAP) to efficiently
construct a variety of intermediates possessing an aryl aminomethyl subunit.
These key compounds are then transformed via selective ring-forming reactions
into heterocyclic scaffolds, each of which possesses suitable functional handles
for further derivatizations and palladium-catalyzed cross coupling reactions. The
modular nature of this approach enables the facile construction of libraries of
polycyclic compounds bearing a broad range of substituents and substitution
patterns for biological evaluation. Screening of several compound libraries thus
produced has revealed a large subset of compounds that exhibit a broad spectrum
of medicinally-relevant activities.
PMID- 25135848
TI - Impact of the Japanese gastric cancer screening system on treatment outcomes in
gastric gastrointestinal stromal tumor (GIST): an analysis based on the GIST
registry.
AB - BACKGROUND: Gastrointestinal stromal tumors (GISTs) of the stomach are found
incidentally during gastric cancer screening in Japan. This study investigated
whether the Japanese gastric cancer screening system helps to improve treatment
outcomes in gastric GIST based on an analysis of the GIST registry conducted by
the Kinki GIST Study Group. METHODS: The registry was designed to collect data on
background characteristics, treatment methods, pathologic characteristics, and
prognosis of GIST from January 2003 through December 2007 at 40 participating
institutions. RESULTS: The study enrolled 672 GIST patients, 482 of whom had
gastric GIST. According to the modified National Institutes of Health consensus
criteria, 22.6 % of the patients were classified as high risk for recurrence,
18.5 % as intermediate risk, 35.9 % as low risk, and 13.9 % as very low risk.
After exclusion of the patients inevaluable for treatment outcome, the study
included 137 symptomatic patients (symptomatic group) and 147 asymptomatic
patients (asymptomatic group). The diagnosis of the asymptomatic patients was
determined through gastric cancer screening. The median tumor size in the
asymptomatic group was significantly smaller than in the symptomatic group (3.5
vs. 5.3 cm; P < 0.0001). The 5-year recurrence-free survival rate in the
asymptomatic high-risk patients (72.4 %) was lower than in their symptomatic
counterparts (46.3 %) (P = 0.017). More patients in the asymptomatic group
underwent laparoscopic surgery (42.2 vs. 27.2 %; P = 0.0081). CONCLUSIONS: By
identifying asymptomatic patients, the Japanese gastric cancer screening system
contributes to early detection of gastric GIST and favorable treatment outcomes.
PMID- 25135849
TI - Open versus endoscopic carpal tunnel release: a meta-analysis of randomized
controlled trials.
AB - BACKGROUND: Carpal tunnel syndrome is a common compressive neuropathy of the
median nerve. The efficacy and safety of endoscopic versus open carpal tunnel
release remain controversial. QUESTIONS/PURPOSES: The purpose of this study was
to determine whether endoscopic compared with open carpal tunnel release provides
better symptom relief, validated outcome scores, short- and long-term strength,
and/or digital sensibility; entails a differential risk of complications such as
nerve injury, scar tenderness, pillar pain, and reoperation; allows an earlier
return to work; and takes less operative time. METHODS: The English-language
literature was searched using MEDLINE, the Cumulative Index to Nursing and Allied
Health Literature, and the Cochrane Central Register of Controlled Trials.
Randomized controlled trials that compared endoscopic and open carpal tunnel
release were included in the meta-analysis. Methodologic quality was assessed
with the Consolidated Standards Of Reporting Trials (CONSORT) checklist, and a
sensitivity analysis was performed. Symptom relief, Boston Carpal Tunnel
Questionnaire (BCTQ) scores, strength, digital sensibility, complications,
reoperation, interval to return to work, and operative time were analyzed. Twenty
one randomized controlled trials containing 1859 hands were included. RESULTS:
Endoscopically treated patients showed similar symptom relief and BCTQ scores;
better early recovery of grip strength (mean difference [MD], 3.03 kg [0.08
5.98]; p = 0.04) and pinch strength (MD, 0.77 kg [0.33-1.22]; p < 0.001) but no
advantage after 6 months; lower risk of scar tenderness (risk ratio [RR], 0.53
[0.35-0.82]; p = 0.005); higher risk of nerve injury (RR, 2.84 [1.08-7.46]; p =
0.03), most of which were transient neurapraxias. Similar risk of pillar pain and
reoperation; an earlier return to work (MD, -8.73 days [-12.82 to -4.65]; p <
0.001); and reduced operative time (MD, -4.81 minutes [-9.23 to -0.39]; p =
0.03). CONCLUSIONS: High-level evidence from randomized controlled trials
indicates that endoscopic release allows earlier return to work and improved
strength during the early postoperative period. Results at 6 months or later are
similar according to current data except that patients undergoing endoscopic
release are at greater risk of nerve injury and lower risk of scar tenderness
compared with open release. While endoscopic release may appeal to patients who
require an early return to work and activities, surgeons should be cognizant of
its elevated incidence of transient nerve injury amid its similar overall
efficacy to open carpal tunnel release. Additional research is required to define
the learning curve of endoscopic release and clarify the influence of surgeon
volume on its safety.
PMID- 25135850
TI - CORR Insights(r): a novel system improves preservation of osteochondral
allografts.
PMID- 25135851
TI - CORR Insights (r): Patient-specific anatomical and functional parameters provide
new insights into the pathomechanism of cam FAI.
PMID- 25135852
TI - CORR Insights: Is synovial C-reactive protein a useful marker for periprosthetic
joint infection?
PMID- 25135853
TI - Editorial comment: 2013 Limb Lengthening and Reconstruction Society.
PMID- 25135854
TI - It is that time of year again ... immunization opportunities for older adults.
PMID- 25135856
TI - Generation of antibodies against membrane proteins.
AB - The monoclonal antibody has become an important therapeutic in the treatment of
both hematological malignancies and solid tumors. The recent success of antibody
drug conjugates (ADCs) has broadened the extent of the potential target molecules
in cancer immunotherapy. As a result, even molecules of low abundance have become
targets for cytotoxic reagents. The multi-pass membrane proteins are an emerging
target for the next generation antibody therapeutics. One outstanding challenge
is the difficulty in preparing a sufficient amount of these membrane proteins so
as to be able to generate the functional antibody. We have pursued the expression
of various membrane proteins on the baculovirus particle and the utilization of
displayed protein for immunization. The strong antigenicity of the virus acts
either as a friend or foe in the making of an efficient antibody against an
immunologically tolerant antigen. This article is part of a Special Issue
entitled: Recent advances in molecular engineering of antibody.
PMID- 25135855
TI - Significance of redox-active cysteines in human FAD synthase isoform 2.
AB - FAD synthase (FMN:ATP adenylyl transferase, FMNAT or FADS, EC 2.7.7.2) is the
last enzyme in the pathway converting riboflavin into FAD. In humans, FADS is
localized in different subcellular compartments and exists in different isoforms.
Isoform 2 (490-amino acids) is organized in two domains: the 3'-phosphoadenosine
5'-phosphosulfate (PAPS) reductase domain, that is the FAD-forming catalytic
domain, and one resembling a molybdopterin-binding (MPTb) domain, with a
hypothetical regulatory role. hFADS2 contains ten Cys residues, seven of which
located in the PAPS reductase domain, with a possible involvement either in FAD
synthesis or in FAD delivery to cognate apo-flavoproteins. A homology model of
the PAPS reductase domain of hFADS2 revealed a co-ordinated network among the Cys
residues in this domain. In this model, C312 and C303 are very close to the
flavin substrate, consistent with a significantly lowered FAD synthesis rate in
C303A and C312A mutants. FAD synthesis is also inhibited by thiol-blocking
reagents, suggesting the involvement of free cysteines in the hFADS2 catalytic
cycle. Mass spectrometry measurements and titration with thiol reagents on wt
hFADS2 and on several individual cysteine/alanine mutants allowed us to detect
two stably reduced cysteines (C139 and C241, one for each protein domain), two
stable disulfide bridges (C399-C402, C303-C312, both in the PAPS domain), and two
unstable disulfides (C39-C50; C440-C464). Whereas the C39-C50 unstable disulfide
is located in the MPTb domain and appears to have no catalytic relevance, a
cysteine-based redox switch may involve formation and breakdown of a disulfide
between C440 and C464 in the PAPS domain.
PMID- 25135857
TI - N-terminal region of human chemokine receptor CXCR3: Structural analysis of
CXCR3(1-48) by experimental and computational studies.
AB - Our study on the highly charged N-terminal peptide of the human chemokine
receptor CXCR3 by spectroscopic methods in solution and by means of molecular
dynamics simulations showed that the charge content modulates the intrinsic
structural preference of its flexible backbone. Collectively, our findings
suggest that the structural organization of a protein should be seen as a part of
a continuum in which the ratio between electrostatic and hydrophobic interactions
and the intrinsic flexibility are important properties used to optimize the
folding. When this ratio changes and the structure is intrinsically flexible, the
structural organization of the system moves along the continuum of the possible
conformational states. By all this combined information, one can describe the
structure of CXCR3(1-48) as an ensemble of conformations. In fact, the peptide
shows stretches of negative charges embedded in a flexible sequence which can be
used to maximize promiscuous interactions relevant to molecular recognition but
globally the peptide appears as a poly-structured globule-like ensemble that is
dynamically stabilized by H-bonds. We have approached the study of the most
populated ensembles with subset selection to explain our experimental data also
by evidencing that the changes into the fraction of charged residues discriminate
between dynamically poly-structured states, conceivably because of small free
energy barriers existing between the different conformations of CXCR3(1-48).
Therefore, the overlap of a highly flexible backbone, negatively charged residues
and sites which can be modified by post-translational modifications represent the
structural organization that controls the molecular mechanisms underlying the
biological functions carried out by CXCR3(1-48).
PMID- 25135858
TI - Soluble epoxide hydrolase activity regulates inflammatory responses and seizure
generation in two mouse models of temporal lobe epilepsy.
AB - Neuroinflammation is known to be involved in epileptogenesis with unclear
mechanisms. Inhibition of soluble epoxide hydrolase (sEH) seems to offer anti
inflammatory protection to ischemic brain injury in rodents. Thus, it is
hypothesized that sEH inhibition might also affect the neuroinflammatory
responses caused by epileptic seizures. In the present study, we investigated the
involvement of sEH in neuroinflammation, seizure generation and subsequent
epileptogenesis using two mouse models of temporal lobe epilepsy. Experimental
epileptic seizures were induced by either pilocarpine or electrical amygdala
kindling in both wild-type (WT) C57BL/6 mice and sEH knockout (sEH KO) mice. The
sEH expression in the hippocampus was detected by immunohistochemistry and
Western blot analysis. The effects of the sEH hydrolase inhibitors, 12-(3
adamantan-1-yl-ureido)-dodecanoic acid (AUDA) and N-[1-(1-oxopropyl)-4
piperidinyl]-N'-[4-(trifluoromethoxy) phenyl)-urea (TPPU), and of the genetic
deletion of sEH on seizure-induced neuroinflammatory responses and the
development of epilepsy were evaluated. In the hippocampus of WT mice, sEH was
mainly expressed in astrocytes (GFAP(+)), neurons (NeuN(+)) and scattered
microglia (Iba-1(+)) in the regions of CA1, CA3 and dentate gyrus. Expression of
sEH was significantly increased on day 7, 14, 21 and 28 after pilocarpine-induced
status epilepticus (SE). Administration with sEH inhibitors attenuated the SE
induced up-regulation of interleukin-1beta (IL-1beta) and interleukin-6 (IL-6),
the degradation of EETs, as well as IkappaB phosphorylation. Following treatment
with AUDA, the frequency and duration of spontaneous motor seizures in the
pilocarpine-SE mice were decreased and the seizure-induction threshold of the
fully kindled mice was increased. Up-regulation of hippocampal IL-1beta and IL-6
was found in both WT and sEH KO mice after successful induction of SE. Notably,
sEH KO mice were more susceptible to seizures than WT mice. Seizure related
neuroinflammation and ictogenesis were attenuated by pharmacological inhibition
of sEH enzymatic activity but not by sEH genetic deletion. Therefore, sEH may
play an important role in the generation of epilepsy. Furthermore, the
effectiveness of AUDA in terms of anti-inflammatory and anti-ictogenesis
properties suggests that it may have clinical therapeutic implication for
epilepsy in the future, particularly when treating temporal lobe epilepsy.
PMID- 25135859
TI - Dexamethasone enhances necrosis-like neuronal death in ischemic rat hippocampus
involving MU-calpain activation.
AB - Transient forebrain ischemia (TFI) leads to hippocampal CA1 pyramidal cell death
which is aggravated by glucocorticoids (GC). It is unknown how GC affect
apoptosis and necrosis in cerebral ischemia. We therefore investigated the co
localization of activated caspase-3 (casp-3) with apoptosis- and necrosis-like
cell death morphologies in CA1 of rats treated with dexamethasone prior to TFI
(DPTI). In addition, apoptosis- (casp-9, casp-3, casp-3-cleaved PARP and cleaved
alpha-spectrin 145/150 and 120kDa) and necrosis-related (calpain-specific casp-9
cleavage, MU-calpain upregulation and cleaved alpha-spectrin 145/150kDa) cell
death mechanisms were investigated by Western blot analysis. DPTI expedited CA1
neuronal death from day 4 to day 1 and increased the magnitude of CA1 neuronal
death from 66.2% to 91.3% at day 7. Furthermore, DPTI decreased the overall (days
1-7) percentage of dying neurons displaying apoptosis-like morphology from 4.7%
to 0.3% and, conversely, increased the percentage of neurons with necrosis-like
morphology from 95.3% to 99.7%. In animals subjected to TFI without dexamethasone
(ischemia-only), 7.4% of all dying CA1 neurons were casp-3-immunoreactive (IR),
of which 3.1% co-localized with apoptosis-like and 4.3% with necrosis-like
changes. By contrast, DPTI decreased the percentage of dying neurons with casp-3
IR to 1.4%, of which 0.3% co-localized with apoptosis-like changes and 1.1% with
necrosis-like changes. Western blot analysis from DPTI animals showed a
significant elevation of MU-calpain, a calpain-produced necrosis-related casp-9
fragment (25kDa) and cleavage of alpha-spectrin into 145/150kDa fragments at day
4, whereas in ischemia-only animals a significant increase of casp-3-cleaved
PARP, cleavage of alpha-spectrin into 145/150 and 120kDa fragments was detected
at day 7. We conclude that DPTI, in addition to augmenting and expediting CA1
neuronal death, causes a shift from apoptosis-like cell death to necrosis
involving MU-calpain activation.
PMID- 25135860
TI - Cirrhosis-associated immune dysfunction: distinctive features and clinical
relevance.
AB - The term cirrhosis-associated immune dysfunction refers to the main syndromic
abnormalities of immune function, immunodeficiency and systemic inflammation that
are present in cirrhosis. The course of advanced cirrhosis, regardless of its
aetiology, is complicated by cirrhosis-associated immune dysfunction and this
constitutes the pathophysiological hallmark of an increased susceptibility to
bacterial infection, distinctive of the disease. Cirrhosis impairs the
homeostatic role of the liver in the systemic immune response. Damage to the
reticulo-endothelial system compromises the immune surveillance function of the
organ and the reduced hepatic synthesis of proteins, involved in innate immunity
and pattern recognition, hinders the bactericidal ability of phagocytic cells.
Systemic inflammation, in form of activated circulating immune cells and
increased serum levels of pro-inflammatory cytokines, is the result of persistent
episodic activation of circulating immune cells from damage-associated molecular
patterns, released from necrotic liver cells and, as cirrhosis progresses, from
pathogen-associated molecular patterns, released from the leaky gut. Cirrhosis
associated immune dysfunction phenotypes switch from predominantly "pro
inflammatory" to predominantly "immunodeficient" in patients with stable ascitic
cirrhosis and in patients with severely decompensated cirrhosis and extra-hepatic
organ failure (e.g. acute-on-chronic liver failure), respectively. These
cirrhosis-associated immune dysfunction phenotypes represent the extremes of a
spectrum of reversible dynamic events that take place during the course of
cirrhosis. Systemic inflammation can affect the functions of tissue somatic cells
and modify the clinical manifestation of cirrhosis. The best characterized
example is the contribution of systemic inflammation to the haemodynamic
derangement of cirrhosis, which correlates negatively with prognosis.
PMID- 25135861
TI - Underestimation of occult hepatitis C virus infection in chronic haemodialysis
and kidney transplant patients.
PMID- 25135862
TI - MicroRNA-199a-5p inhibition enhances the liver repopulation ability of human
embryonic stem cell-derived hepatic cells.
AB - BACKGROUND & AIMS: Current hepatic differentiation protocols for human embryonic
stem cells (ESCs) require substantial improvements. MicroRNAs (miRNAs) have been
reported to regulate hepatocyte cell fate during liver development, but their
utility to improve hepatocyte differentiation from ESCs remains to be
investigated. Therefore, our aim was to identify and to analyse hepatogenic
miRNAs for their potential to improve hepatocyte differentiation from ESCs.
METHODS: By miRNA profiling and in vitro screening, we identified miR-199a-5p
among several potential hepatogenic miRNAs. Transplantation studies of miR-199a
5p-inhibited hepatocyte-like cells (HLCs) in the liver of immunodeficient
fumarylacetoacetate hydrolase knockout mice (Fah(-/-)/Rag2(-/-)/Il2rg(-/-)) were
performed to assess their in vivo liver repopulation potential. For target
determination, western blot and luciferase reporter assay were carried out.
RESULTS: miRNA profiling revealed 20 conserved candidate hepatogenic miRNAs. By
miRNA screening, only miR-199a-5p inhibition in HLCs was found to be able to
enhance the in vitro hepatic differentiation of mouse as well as human ESCs. miR
199a-5p inhibition in human ESCs-derived HLCs enhanced their engraftment and
repopulation capacity in the liver of Fah(-/-)/Rag2(-/-)/Il2rg(-/-) mice.
Furthermore, we identified SMARCA4 and MST1 as novel targets of miR-199a-5p that
may contribute to the improved hepatocyte generation and in vivo liver
repopulation. CONCLUSIONS: Our findings demonstrate that miR-199a-5p inhibition
in ES-derived HLCs leads to improved hepatocyte differentiation. Upon
transplantation, HLCs were able to engraft and repopulate the liver of Fah(-/
)/Rag2(-/-)/Il2rg(-/-) mice. Thus, our findings suggest that miRNA modulation may
serve as a promising approach to generate more mature HLCs from stem cell sources
for the treatment of liver diseases.
PMID- 25135863
TI - Vitamin D level and sustained virologic response to interferon-based antiviral
therapy in chronic hepatitis C: a systematic review and meta-analysis.
AB - BACKGROUND & AIMS: The baseline 25-hydroxyvitamin D (25[OH]D) level has recently
been reported to be an independent predictor of sustained virologic response
(SVR) to treatment with pegylated interferon (PEG-IFN) plus ribavirin (RBV) for
chronic hepatitis C virus (HCV) infection. However, studies have yielded
inconsistent results. Thus, we conducted a systematic review and meta-analysis to
clarify any association between baseline 25(OH)D level and SVR in HCV therapy.
METHODS: Two reviewers searched four electronic databases (Medline, Embase,
PubMed, and Cochrane trials register) and relevant international conference
proceedings up to March 2014 for studies treating chronic HCV infection with PEG
IFN plus RBV where baseline 25(OH)D level was tested. Studies involving patients
with HIV co-infection, previous liver transplantation or those receiving vitamin
D supplementation were excluded. The mean baseline 25(OH)D level was compared
between those who achieved and those who failed to achieve SVR. Pooled standard
difference in mean 25(OH)D level, odds ratios (OR) and 95% confidence intervals
(CI) were calculated with the Comprehensive Meta-Analysis software (version 2.0)
using a random effects model. RESULTS: 11 studies comprising 2605 patients were
included in the meta-analysis. There was no significant association between the
baseline mean 25(OH)D level and SVR (OR 1.44, 95% CI 0.92-2.26; p=0.11), either
in patients infected with genotypes 1/4/5 (OR 1.48, 95% CI 0.94-2.34; p=0.09) or
genotypes 2/3 (OR 1.51, 95% CI 0.26-8.87; p=0.65). CONCLUSIONS: The baseline
25(OH)D level is not associated with SVR to PEG-IFN plus RBV therapy in chronic
HCV infection, regardless of genotype. Any effect of vitamin D supplementation on
SVR is yet to be definitively determined.
PMID- 25135864
TI - PegIFNalpha/ribavirin/protease inhibitor combination in severe hepatitis C virus
associated mixed cryoglobulinemia vasculitis.
AB - BACKGROUND & AIMS: The aim of this study was to analyse the safety and efficacy
of the PegIFNalpha/ribavirin/protease inhibitor combination in severe and/or
refractory hepatitis C virus (HCV)-mixed cryoglobulinemia (MC) vasculitis.
METHODS: This prospective cohort study included 30 patients (median age 59 years
[53-66] and 57% of women) with HCV-MC vasculitis. PegIFNalpha/ribavirin (for 48
weeks) was associated with telaprevir (375 mg three times daily, for 12 weeks, [n
= 17]) or boceprevir (800 mg three times daily, for 44 weeks, (n = 13]). RESULTS:
Twenty three patients (76.7%) were non-responders to previous antiviral therapy.
At week 72, twenty patients (66.7%) were complete clinical and sustained
virological responders. The cryoglobulin level decreased from 0.45 to 0 g/L
(p<0.0001) and the C4 level increased from 0.09 to 0.14 g/L (p = 0.017). Complete
clinical responders had a higher frequency of purpura (16/20 [80%] vs. 4/10
[40%], p = 0.045), and a trend towards lower frequency of neuropathy (9/20 (45%)
vs. 8/10 [80%], p = 0.12) compared with partial responders. Serious adverse
events occurred in 14 patients (46.6%) during the 72 weeks of follow-up. Twenty
eight patients (93.3%) received erythropoietin, 14 (46.6%) had red blood cell
transfusion and 2 (6.6%) received granulocyte stimulating agent. The baseline
factors associated with serious adverse events included liver fibrosis (p =
0.045) and a low platelet count (p = 0.021). CONCLUSIONS: The
PegIFNalpha/ribavirin/protease inhibitor combination is highly effective in
severe and/or refractory HCV-MC at the cost of frequent side effects. Baseline
platelet count and liver fibrosis are useful in guiding treatment decisions.
PMID- 25135865
TI - Advantage of bariatric surgery for patients with type 2 diabetes mellitus.
PMID- 25135866
TI - Reply to: "underestimation of occult hepatitis C virus infection in chronic
haemodialysis and kidney transplant patients".
PMID- 25135869
TI - Revascularization of living-donor kidney transplant with multiple arteries: long
term outcomes using the inferior epigastric artery.
AB - OBJECTIVE: To study the safety and long-term outcomes of use of the inferior
epigastric artery (IEA) for revascularization of small accessory kidney arteries
(3 mm or less). MATERIALS AND METHODS: Data of 602 living-donor kidney
transplants were reviewed. Age was 37.4 +/- 15 years (range, 3-78 years).
Multiple arteries were present in 98 kidneys (16.3%); of these, 83 (84.7%) had 2
and arteries and 15 (15.3%) had 3 arteries. In 21 kidneys (21.4%) with multiple
arteries (group I [GI]), the IEA was used for reconstruction. Four (14.3%) had 3
arteries, and 17 (85.7%) had 2 arteries. In 77 patients (group II [GII]), the
inferior accessory renal artery was reconstructed with a side-to-side or an end
to-side anastomosis to the main renal artery. Follow-up was 43.8 +/- 38.1 months
(range, 1-124 months). The Fisher exact test and the 2-tailed t test were used
for statistical analysis. RESULTS: Delayed graft function occurred in 1 GI
patient (4.8%) and in 5 GII patients (6.5%; P >.05). One partial renal infarction
occurred in each group (4.8% vs 1.3%; P >.05). There was 1 urinary fistula in GI
and 3 urinary fistulas and 1 ureteral stenosis in GII (P >.05). One graft (4.8%)
lost function in GI and 5 (6.5%) in GII (P >.05). Eleven patients (53.4%) were
hypertensive in GI and 53 (68.8%) in GII (P >.05). CONCLUSION: The use of the IEA
for revascularization of a living-donor kidney transplant with multiple arteries
is safe and effective, yielding similar long-term outcomes compared with the
standard technique. Use of the IEA avoids the risks of manipulation of the main
renal artery.
PMID- 25135867
TI - Statin use is associated with a reduced risk of fibrosis progression in chronic
hepatitis C.
AB - BACKGROUND & AIMS: Therapies that slow fibrosis progression in chronic liver
disease are needed. Animal models have demonstrated that statins prevent the
progression of hepatic fibrosis, but human data is lacking so far. We evaluated
the association between statins and fibrosis progression in the HALT-C trial
cohort. METHODS: Subjects with chronic hepatitis C (CHC) and advanced hepatic
fibrosis underwent serial liver biopsies over 3.5 years. The primary outcome was
a ? 2-point increase in the Ishak fibrosis score on at least one of two serial
biopsies. We used complementary log-log regression analysis to assess the
association between statins and fibrosis progression among subjects without
baseline cirrhosis. RESULTS: Fibrosis progression occurred in 3/29 (10%) statin
users and 145/514 (29%) non-users. The unadjusted hazard ratio (HR) for fibrosis
progression among statin users compared to non-users was 0.32 (95% CI 0.10-0.99).
This association remained significant after adjusting for established predictors
of histological outcome, including body mass index, platelets and hepatic
steatosis (adjusted HR 0.31; 95% CI 0.10-0.97). The mean change in Ishak fibrosis
score over the 3.5 year study period was -0.34 (SE 0.18) for statin users
compared to +0.42 (SE 0.07) for non-users (p = 0.006, after adjustment for
baseline fibrosis score). CONCLUSIONS: Statin use is associated with a reduced
risk of fibrosis progression in advanced CHC. Our findings suggest a potential
role for statins in preventing liver disease progression.
PMID- 25135868
TI - The genomic landscape of hepatoblastoma and their progenies with HCC-like
features.
AB - BACKGROUND & AIMS: Hepatoblastoma (HB) is the most common childhood liver cancer
and occasionally presents with histological and clinical features reminiscent of
hepatocellular carcinoma (HCC). Identification of molecular mechanisms that drive
the neoplastic continuation towards more aggressive HCC phenotypes may help to
guide the new stage of targeted therapies. METHODS: We performed comprehensive
studies on genetic and chromosomal alterations as well as candidate gene function
and their clinical relevance. RESULTS: Whole-exome sequencing identified HB as a
genetically very simple tumour (2.9 mutations per tumour) with recurrent
mutations in beta-catenin (CTNNB1) (12/15 cases) and the transcription factor
NFE2L2 (2/15 cases). Their HCC-like progenies share the common CTNNB1 mutation,
but additionally exhibit a significantly increased mutation number and
chromosomal instability due to deletions of the genome guardians RAD17 and TP53,
accompanied by telomerase reverse-transcriptase (TERT) promoter mutations.
Targeted genotyping of 33 primary tumours and cell lines revealed CTNNB1, NFE2L2,
and TERT mutations in 72.5%, 9.8%, and 5.9% of cases, respectively. All NFE2L2
mutations affected residues of the NFE2L2 protein that are recognized by the
KEAP1/CUL3 complex for proteasomal degradation. Consequently, cells transfected
with mutant NFE2L2 were insensitive to KEAP1-mediated downregulation of NFE2L2
signalling. Clinically, overexpression of the NFE2L2 target gene NQO1 in tumours
was significantly associated with metastasis, vascular invasion, the adverse
prognostic C2 gene signature, as well as poor outcome. CONCLUSIONS: Our study
demonstrates the importance of CTNNB1 mutations and NFE2L2-KEAP1 pathway
activation in HB development and defines loss of genomic stability and TERT
promoter mutations as prominent characteristics of aggressive HB with HCC
features.
PMID- 25135870
TI - Reconstructive strategy and classification of penoscrotal defects.
AB - OBJECTIVE: To classify defects in the penoscrotal region according to their
specific anatomic sites. METHODS: From January 2002 to December 2012, 20 male
patients underwent reconstruction for penoscrotal defects. The causative factors
were Fournier's gangrene in 12 patients, extramammary Paget's disease in 4, skin
tumors in 3, and deformity after a burn injury in 1. The defects were categorized
according to their anatomic location: penis (P), and right (r) and left (l)
scrotum (Sr and Sl), inguinal area (Ir and Il), and perianal area (Ar and Al).
RESULTS: Seven patients with defects in the penis received skin grafts. Defects
affecting more than 2 anatomic regions or extensive defects (>100 cm(2)) were
reconstructed by free tissue transfer. Other defects were reconstructed by
perforator-based island flap coverage. All of the flaps survived without
complications. CONCLUSION: We introduce a classification that provides a simple
way to specify the anatomic location and extent of a defect. This classification
will permit more effective and straightforward reconstruction in the penoscrotal
region.
PMID- 25135872
TI - Comparison of treatment strategies for thoracic endograft infection.
AB - OBJECTIVE: Endograft infection after thoracic endovascular aortic repair (TEVAR)
is associated with a substantial mortality rate that exceeds 70% in the largest
published series. The aim of this study was to review all published reports on
infection after TEVAR treated with either preservation of the endograft or
surgical excision of the stent graft with the intention of providing a comparison
of the safety, efficacy, and durability of the two different treatment
strategies. METHODS: An extensive electronic health database search was
undertaken to identify all articles that were published up to December 2013
reporting on endograft infection after TEVAR. Overall, 55 patients treated with
endograft preservation (group A) and 41 patients treated with endograft
explantation (group B) were included in this review. RESULTS: The most frequently
isolated microorganisms were Streptococcus species (29.4%) and Staphylococcus
species (29.4%). The mortality for both groups was 66.6%. The in-hospital
mortality rate in group A was 42% and reached 81.8% in a mean follow-up period of
8.6 months. The in-hospital mortality rate in group B was 36.6%. Four (9.7%)
further deaths due to reinfection or fistula recurrence were recorded in a mean
follow-up period of 15.3 months, leading to an overall mortality of 46.3%. The
meta-analysis showed a trend of better outcome with endograft explantation
compared with endograft preservation (odds ratio [OR], 0.52; 95% confidence
interval [CI], 0.18-1.48). In group A, a trend of better outcome was revealed
when drainage and repair of the fistula were applied (OR, 2.22; 95% CI, 0.55
8.90). A trend of worse outcomes was detected in fistula patients compared with
nonfistula patients (OR, 1.26; 95% CI, 0.43-3.74). CONCLUSIONS: Endograft
preservation seems not a durable option. It can be offered to patients who refuse
surgery or as a palliative option or bridging procedure for severely ill
patients. Compared with antibiotic therapy alone, antibiotic therapy followed by
drainage and repair of the fistula may control the sepsis, providing, however,
mainly a temporary benefit. The presence of fistula is a predictor of dismal
outcome. Endograft explantation remains the "gold standard" of treatment. The
mortality rate of surgical conversion is much higher in the presence of fistula.
PMID- 25135871
TI - Evaluation of neutrophil gelatinase-associated lipocalin, interleukin-18, and
cystatin C as molecular markers before and after unilateral shock wave
lithotripsy.
AB - OBJECTIVE: To investigate the impact of shock wave lithotripsy (SWL) on renal
tissues using neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, and
interleukin 18 (IL-18) levels in serum and urine and to examine the relationship
of these biomarkers with patient and calculus characteristics as well as SWL
treatment parameters. MATERIALS AND METHODS: Thirty-seven patients with renal
calculi were included in this study. Blood and urine samples were attained from
each patient at 4 time points; immediately before SWL, 6 hours after, 3 days
after, and 10 days after the SWL. A new generation lithotripter was used for all
cases. Serum and urine NGAL concentrations were measured using commercially
available enzyme-linked immunosorbent assay kits according to manufacture's
protocol. The concentration of cystatin C was measured in serum, whereas IL-18
concentration was assessed in urine. RESULTS: There were no statistically
significantly differences in the levels of NGAL in serum and urine before and
after SWL. The mean levels of cystatin C in serum appeared significantly higher 3
and 10 days after SWL. No statistically significant differences were identified
between levels of IL-18 before and after SWL. Patients with diabetes mellitus
demonstrated significantly higher baseline cystatin C levels. There was no
correlation between calculus characteristics or treatment parameters and the
levels of all 3 biomarkers after SWL. CONCLUSION: The results of this study
indicate that SWL is associated with minimal acute injury to renal tissues. Our
findings support the safety profile of new generation lithotripters, provided
orthodox indications and treatment principles are followed.
PMID- 25135874
TI - The impact of intraoperative shunting on early neurologic outcomes after carotid
endarterectomy.
AB - BACKGROUND: Although the need for intraoperative shunting during carotid
endarterectomy (CEA) is intensely debated, relatively few studies have compared
the neurologic outcomes of patients undergoing CEA with or without shunts. The
objective of our analysis was to determine the impact of intraoperative shunting
during CEA on the incidence of postoperative stroke. METHODS: The 2012 CEA
targeted American College of Surgeons National Surgical Quality Improvement
Program database was used for this analysis. The preoperative and operative
characteristics of patients undergoing CEA with or without intraoperative
shunting were compared. From this overall sample, propensity score techniques
were then used to match patients with or without intraoperative shunting for a
number of variables, including age, degree of ipsilateral and contralateral
carotid stenosis, presence of several anatomic or physiologic risk factors,
anesthesia modality, and use of patch angioplasty vs primary arteriotomy closure.
The 30-day postoperative mortality and combined stroke/transient ischemic attack
(TIA) rates of this matched cohort were then compared. A similar analysis was
also performed on a subgroup of patients with severe stenosis or occlusion of the
contralateral carotid artery. RESULTS: A total of 3153 patients were included for
initial analysis (2023 "no-shunt" patients vs 1130 "shunt" patients). From this
overall sample, propensity score matching yielded a cohort of 1072 patients with
or without intraoperative shunt placement who were well matched for all known
patient- and procedure-related factors. There was no significant difference in
the incidence of postoperative stroke/TIA between the two groups of this matched
cohort (3.4% in the no-shunt group vs 3.7% in the shunt group; P = .64). Analysis
of a similarly well matched subgroup of patients with severe stenosis or
occlusion of the contralateral carotid artery demonstrated a statistically
nonsignificant increase in the incidence of postoperative stroke/TIA with the use
of intraoperative shunting (4.9% in the no-shunt group vs 9.8% in the shunt
group; P = .08). CONCLUSIONS: There is no clinical benefit to intraoperative
shunting during CEA, even in patients who may be at high risk for intraoperative
cerebral hypoperfusion due to severe stenosis or occlusion of the contralateral
carotid artery.
PMID- 25135873
TI - One-year patency rate of native arteriovenous fistulas reconstructed by vascular
stripping in hemodialysis patients with venous neointimal hyperplasia.
AB - OBJECTIVE: There are limited therapeutic measures for stenosis of arteriovenous
fistulas (AVFs) due to venous neointimal hyperplasia (VNH). In the current
retrospective study, we reviewed the clinical data of hemodialysis patients who
underwent AVF reconstruction by VNH stripping. The primary measure of interest
was the secondary patency rate of the restored AVF. METHODS: The study included
hemodialysis patients who underwent AVF reconstruction by VNH stripping (group
A), AVF reconstruction proximal to the original fistula (group B), or creation of
a new AVF (group C). Patency was evaluated immediately after the surgery and at
follow-up visits. RESULTS: Of 353 patients who underwent AVF reconstructions, 327
(91.9%) were for late AVF failure. The final analysis included 305 patients: 76,
128, and 101 patients in groups A, B, and C, respectively. The three groups were
comparable in age, sex, causes for AVF, AVF sites, and the artery for the AVF (P
> .05). At 3-month follow-up, the secondary AVF patency rate was comparable
across the three groups at 93.4%, 92.2%, and 92.1% in groups A, B, and C,
respectively. The patency rate at 6 and 12 months was also comparable across
groups A, B, and C at 89.5%, 89.8%, and 88.1% at 6 months and 84.2%, 85.9%, and
81.2% at 12 months, respectively. CONCLUSIONS: Reconstructing the AVF by
surgically removing VNH is an effective technique for late hemodialysis access
failure, with maximal preservation of blood vessels.
PMID- 25135875
TI - Percutaneous radial access for peripheral transluminal angioplasty.
AB - OBJECTIVE: The radial approach is currently gaining popularity in the setting of
coronary percutaneous transluminal angioplasty (PTA) because it decreases the
incidence of vascular complications. This study reports our initial results with
radial access for peripheral PTA. METHODS: Between November 2011 and January
2014, we performed peripheral PTA in 526 patients. PTA was performed through left
radial access in 24 ambulatory patients (4.6%) presenting with TransAtlantic
Inter-Society Consensus A or B lesions on preoperative computed tomography
angiography. Materials included a 110-cm-long introducer, a 0.018-inch 400-cm
long wire, 150-cm-long angiography catheters, 180-cm-long shaft balloons and
stents. Data were prospectively collected. RESULTS: There were 22 men (92%),
median age was 65 years (range, 45-88 years), and 38 target lesions were treated.
Indication for revascularization was disabling claudication in 22 patients (92%)
and critical ischemia in two (8%). Indication for choosing the radial approach
was bilateral hostile groins in 12 patients (50%), bilateral infrainguinal
lesions in 4 (17%), need for a contralateral femoral approach in the setting of
kissing iliac stents or bifurcated surgical aortic grafts in 3 (13%), and
elective in 5 (21%). Radial puncture failed in one patient (4%), and PTA was
performed through brachial access. Technical success was 91% (20 of 22 patients).
Thirty-seven stents were implanted. Total procedure duration was 45 minutes
(range, 30-120 minutes). Fluoroscopy time was 9 minutes (range, 5-35 minutes),
and 40 mL (range, 20-90 mL) of contrast was necessary. Radial artery rupture
secondary to spasm was noted at the end of the procedure in two patients (8%).
All patients could ambulate 2 hours after the procedure. No patient died. Median
follow-up was 8 months (range, 1-23 months). Three radial arteries (13%) were
occluded at the last follow-up. At 6 months, freedom from target lesion
revascularization and target vessel revascularization were 91% and 91%,
respectively, for iliac lesions and 93% and 86%, respectively, for infrainguinal
lesions. CONCLUSIONS: This study demonstrates the feasibility of radial access
for peripheral PTA. Radial access could represent an alternative to brachial
access for peripheral and visceral interventions. Although complication rates of
the present series are concerning, larger studies are needed to determine the
role of transradial PTA once the learning curve is overcome. A wider diffusion of
the technique mandates (1) smaller-diameter sheaths, (2) longer shaft devices,
and (3) the development of specifically designed rescue devices such as covered
stents and thromboaspiration catheters.
PMID- 25135876
TI - Professionalism and the work-life balance.
PMID- 25135877
TI - Computed tomography-guided reoperation for neurogenic thoracic outlet syndrome.
AB - OBJECTIVE: Persistent or recurrent symptoms after surgical treatment for
neurogenic thoracic outlet syndrome (nTOS) is a problem commonly encountered by
high-volume referral centers. The mechanical etiology patterns at reoperation
include (1) inadequate previous rib resection, (2) rib regrowth, (3) scar tissue
formation, or (4) intact scalene muscle. Reoperative TOS surgery has significant
potential morbidity, and therefore, careful patient selection and meticulous
planning are required. This study evaluated the utility of multidetector computed
tomography (CT) in the differential diagnosis of patients with recurrent or
persistent nTOS. METHODS: A retrospective record review was performed of a nTOS
referral practice of patients treated from 2003 to 2012 to focus on patients
reoperated on for recurrent or persistent symptoms. In 2003, a dedicated high
resolution multidetector TOS CT protocol was established to assist in clinical
decision making and reoperative planning. A single designated radiologist
interpreted all CT images. Imaging, patient clinical characteristics,
interventions, and outcomes were reviewed. RESULTS: The study group included 20
reoperations for recurrent (n = 15) or persistent (n = 5) symptoms. Mean age was
35 years, and 60% of redo cases were in women. Preoperative CT imaging
demonstrated the following anatomic patterns: inadequate previous rib resection
in 5 (25%), rib regrowth in 5 (25%), scar tissue formation in 10 (50%), and
intact scalene muscle in 3 (15%). Operative findings concurred with preoperative
imaging in 85% of patients. There were no neurovascular injuries and no major
complications. At a mean follow-up of 43 months, improvement or resolution of
symptoms was significant in nine patients (45%), moderate in seven (35%), and
minimal in four (20%). CONCLUSIONS: Recurrent/persistent nTOS is an often-vexing
problem with challenging solutions. These results demonstrate the utility of a
TOS protocol CT scan in providing correlative objective findings and in assisting
with reoperative planning. Positive radiographic findings that correlate with
patient symptoms inform the decision to reoperate.
PMID- 25135880
TI - Obstetrics-based clinical immersion of a multinational team of biomedical
engineering students in Ghana.
PMID- 25135879
TI - NG as a novel nitric oxide donor induces apoptosis by increasing reactive oxygen
species and inhibiting mitochondrial function in MGC803 cells.
AB - NG, O(2)-(2,4-dinitro-5-{[2-(12-en-28-beta-D-galactopyranosyl-oleanolate-3-yl)
oxy-2-oxoethyl] amino} phenyl) 1-(N-hydroxyethylmethylamino) diazen-1-ium-1,2
diolate, was identified in our laboratory as a novel nitric oxide-releasing
prodrug with antitumor effects. A previous study showed that NG inhibited cell
growth, and induced apoptosis in HepG2 cells. In this study, the inhibitory
effects of NG on the viability of MGC803 cells were examined using
methylthiazolyl tetrazolium biomide (MTT) assay, neutral red assay and trypan
blue exclusion test. The results showed that NG had strong cytotoxicity to induce
apoptosis, which was characterized by a significant externalization of
phosphatidylserine, nuclear morphological changes and enhanced Bax-to-Bcl-2
ratio. Moreover, the release of cytochrome c (Cyt c) from mitochondria and the
activation of caspase-9/3 were also detected, indicating that NG may induce
apoptosis through a mitochondrial-mediated pathway. NG induced mitochondrial
dysfunction in MGC803 cells by altering membrane potential (?Psim), the
inhibition of complexes I, II and IV consequently decreasing ATP level.
Furthermore, the treatment of MGC803 cells with NG caused a marked rise in
oxidative stress as characterized by accumulation of reactive oxygen species
(ROS), excessive malondialdehyde (MDA) production and a reduction in glutathione
hormone (GSH) level and superoxide dismutase (SOD) and glutathione peroxidase
(GSH-Px) activity. In addition, pretreatment with N-acetylcysteine (NAC), a GSH
synthesis precursor, was partially protective against the NG-induced ROS
generation and cell apoptosis. In contrast, pretreatment of MGC803 cells with L
buthionine-S, R-sulfoximine (BSO), a GSH synthesis inhibitor, increased the ROS
levels, and aggravated cell apoptosis by NG. These results suggest that NG
induced apoptosis in MGC803 cells is mediated, at least in part, by the increase
in ROS production, oxidative stress and mitochondrial dysfunction.
PMID- 25135878
TI - Ubiquitin-hepatitis B core antigen-cytoplasmic transduction peptide enhances HBV
specific humoral and CTL immune responses in vivo.
AB - Therapeutic strategies based on an enhanced hepatitis B virus (HBV)-specific
cytotoxic T lymphocyte (CTL) activity may eradicate HBV. We previously verified
that a fusion protein ubiquitin (Ub)-hepatitis B core antigen (HBcAg)-cytoplasmic
transduction peptide (CTP) can enter the cytoplasm of dendritic cells and enhance
T cell response to generate HBV-specific CTLs efficiently in vitro. Ub, a marker
of protein degradation, may promote the generation of peptides appropriate for
major histocompatibility complex class I presentation. In the present study, the
specific immune responses of the fusion protein Ub-HBcAg-CTP in BALB/c mice were
evaluated and the underlying mechanisms were investigated. Results showed that Ub
HBcAg-CTP increased the anti-HBcAg titer and produced the cytokines IFN-gamma and
IL-2. This fusion protein also induced higher percentages of IFN-gamma(+)CD8(+)
cells and specific CTL responses. Ub-HBcAg-CTP could also upregulate the
expressions of Jak2, Tyk2, STAT1, and STAT4 in T lymphocytes. In conclusion, Ub
HBcAg-CTP enhanced cellular and humoral immune responses and induced robust HBV
specific CTL activities in BALB/c mice.
PMID- 25135881
TI - Factors associated with the use of prenatal corticosteroids in the management of
preterm delivery in Chinese hospitals.
AB - OBJECTIVE: To assess the prevalence of the use of prenatal corticosteroids (PCS)
in the management of preterm delivery and the factors associated with PCS
administration. METHODS: A secondary analysis was performed of a cross-sectional
study conducted in 21 Chinese healthcare facilities between November 2010 and
January 2011. The medical records of women who delivered preterm were reviewed.
Associations between PCS administration and individual and organizational-level
factors were determined. RESULTS: The study population comprised 659 women who
delivered at 20 facilities. PCS were given to 158 (68.1%) of 232 women delivering
after 27-34 weeks of pregnancy and 119 (27.9%) of 427 delivering after 35-36
weeks. Teenaged girls were less likely to receive PCS after 27-34 weeks than were
women aged 20-35 years (odds ratio [OR] 0.22; 95% confidence interval [CI] 0.07
0.70). Among women who delivered after 35-36 weeks, the odds of receiving PCS
were lower in urban hospitals than in periurban or rural hospitals (OR 0.04; 95%
CI 0.00-0.44), and there was significant hospital-level variance with regard to
the administration of PCS (P<0.05). CONCLUSION: Generally, PCS were
underprescribed to women at risk of preterm delivery and many women received the
treatment after 35-36 weeks of pregnancy, when it might not have been effective.
PMID- 25135882
TI - Overweight Misperception among Adolescents in the United States.
AB - The purpose of this study was to examine the discrepancies between perceived and
reported overweight status among U.S. adolescents (n>70,000), and to identify
factors contributing to such discrepancies. We used the YRBSS data (years 2001
2009) and found statistically significant, gender and race specific discrepancies
between perceived and reported overweight status. Factors such as BMI, school
performance, and being sexually active are additional predictors of overweight
misperception. The findings suggest that evidence based strategies should be
employed to help adolescents establish correct weight perception. These
strategies should also be tailored based on gender, race, and weight perception
of target audience.
PMID- 25135883
TI - Using the theory of planned behavior to understand caregivers' intention to serve
sugar-sweetened beverages to non-Hispanic black preschoolers.
AB - The purpose of this correlational study was to determine the ability the Theory
of Planned Behavior (TPB) to explain caregivers' intention to serve sugar
sweetened beverages to non-Hispanic black preschoolers. A sample of 165
caregivers of non-Hispanic black children preschoolers completed a written
questionnaire. Multiple regression with path analysis confirmed the relationships
of attitude and subjective norm, but not perceived behavioral control (PBC),with
intention. After removing PBC, the model accounted for 45.1% of variance in
intention. Nurses and other health care professionals can use these findings to
tailor behaviorally-based obesity prevention programs at the individual, family,
and community-based levels.
PMID- 25135884
TI - An in vitro assay to study chikungunya virus RNA synthesis and the mode of action
of inhibitors.
AB - Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that causes
severe persistent arthralgia. To better understand the molecular details of CHIKV
RNA synthesis and the mode of action of inhibitors, we have developed an in vitro
assay to study CHIKV replication/transcription complexes isolated from infected
cells. In this assay (32)P-CTP was incorporated into the CHIKV genome, subgenomic
(sg) RNA and into a ~7.5 kb positive-stranded RNA, termed RNA II. We mapped RNA
II, which was also found in CHIKV-infected cells, to the 5' end of the genome up
to the start of the sgRNA promoter region. Most of the RNA-synthesizing activity,
negative-stranded RNA and a relatively large proportion of nsP1 and nsP4 were
recovered from a crude membrane fraction obtained by pelleting at 15,000 G: .
Positive-stranded RNA was mainly found in the cytosolic S15 fraction, suggesting
it was released from the membrane-associated replication/transcription complexes
(RTCs). The newly synthesized RNA was relatively stable and remained protected
from cellular nucleases, possibly by encapsidation. A set of compounds that
inhibit CHIKV replication in cell culture was tested in the in vitro RTC assay.
In contrast to 3'dNTPs, chain terminators that acted as potent inhibitors of RTC
activity, ribavirin triphosphate and 6-aza-UTP did not affect the RNA
synthesizing activity in vitro. In conclusion, this in vitro assay for CHIKV RNA
synthesis is a useful tool for mechanistic studies on the RTC and mode of action
studies on compounds with anti-CHIKV activity.
PMID- 25135885
TI - Two amino acid substitutions in the haemagglutinin of the 2009 pandemic H1N1
virus decrease direct-contact transmission in guinea pigs.
AB - The 2009 pandemic H1N1 influenza A virus spread across the globe and caused the
first influenza pandemic of the 21st century. Many of the molecular factors that
contributed to the airborne transmission of this pandemic virus have been
determined; however, the direct-contact transmission of this virus remains poorly
understood. In this study, we report that a combination of two mutations (N159D
and Q226R) in the haemagglutinin (HA) protein of the representative 2009 H1N1
influenza virus A/California/04/2009 (CA04) caused a switch in receptor binding
preference from the alpha2,6-sialoglycan to the alpha2,3-sialoglycan receptor,
and decreased the binding intensities for both glycans. In conjunction with a
significantly decreased replication efficiency in the nasal epithelium, this
limited human receptor binding affinity resulted in inefficient direct-contact
transmission of CA04 between guinea pigs. Our findings highlight the role of the
HA gene in the transmission of the influenza virus.
PMID- 25135886
TI - Sporothrix schenckii complex biology: environment and fungal pathogenicity.
AB - Sporothrix schenckii is a complex of various species of fungus found in soils,
plants, decaying vegetables and other outdoor environments. It is the
aetiological agent of sporotrichosis in humans and several animals. Humans and
animals can acquire the disease through traumatic inoculation of the fungus into
subcutaneous tissue. Despite the importance of sporotrichosis, it being currently
regarded as an emergent disease in several countries, the factors driving its
increasing medical importance are still largely unknown. There have only been a
few studies addressing the influence of the environment on the virulence of these
pathogens. However, recent studies have demonstrated that adverse conditions in
its natural habitats can trigger the expression of different virulence factors
that confer survival advantages both in animal hosts and in the environment. In
this review, we provide updates on the important advances in the understanding of
the biology of Spor. schenckii and the modification of its virulence linked to
demonstrated or putative environmental factors.
PMID- 25135887
TI - Adventitious agents in viral vaccines: lessons learned from 4 case studies.
AB - Since the earliest days of biological product manufacture, there have been a
number of instances where laboratory studies provided evidence for the presence
of adventitious agents in a marketed product. Lessons learned from such events
can be used to strengthen regulatory preparedness for the future. We have
therefore selected four instances where an adventitious agent, or a signal
suggesting the presence of an agent, was found in a viral vaccine, and have
developed a case study for each. The four cases are: a) SV40 in polio vaccines;
b) bacteriophage in measles and polio vaccines; c) reverse transcriptase in
measles and mumps vaccines; and d) porcine circovirus and porcine circovirus DNA
sequences in rotavirus vaccines. The lessons learned from each event are
discussed. Based in part on those experiences, certain scientific principles have
been identified by WHO that should be considered in regulatory risk evaluation if
an adventitious agent is found in a marketed vaccine in the future.
PMID- 25135888
TI - The management of secondary lower limb lymphoedema in cancer patients: a
systematic review.
AB - BACKGROUND: Lower limb lymphoedema is a recognised complication of cancer
commonly encountered in palliative care, associated with reduced mobility and
poor quality of life. AIM: To evaluate the available evidence for the treatment
of secondary lower limb lymphoedema in patients with malignancies. DESIGN: A
systematic review of the literature. DATA SOURCES: The MEDLINE, Embase, LILACS,
Science Citation Index, Cochrane Databases and conference proceedings for
published data from date of inception to July 2014 were searched. Relevant
unpublished studies via relevant databases, Internet searches and hand-searches
of the bibliographies of relevant papers were performed. RESULTS: From 1617
citations, 32 papers were selected for full-text assessment. Two randomised
trials and five observational studies were identified. The two randomised
controlled trials evaluated graded compression stockings and Coumarin capsules,
respectively. The five observational studies evaluated lymphovenous microsurgical
shunts, pneumatic compression devices, compression bandages alone, manual
lymphatic drainage with compression and a herbal remedy combining Coumarin,
Ginkgo and Melitoto (with or without manual lymphatic drainage), respectively.
The extracted studies showed substantial heterogeneity. Hence, a meta-analysis
was inappropriate and not performed. CONCLUSION: Few studies have evaluated the
clinical effectiveness and potential side effects of treatments for lower limb
lymphoedema. Moreover, symptoms and quality-of-life assessments were
inconsistently reported. All included studies report lower limb volume reduction
after treatment, which includes complex decongestion therapy, graded compression
stockings and lymphovenous microsurgical shunts. Adequately powered randomised
controlled trials of these interventions are recommended. Effort should be made
to establish standardised outcomes, to minimise bias and to improve reporting
quality in future trials of treatment for lower limb lymphoedema.
PMID- 25135889
TI - The role of phage display in therapeutic antibody discovery.
AB - Phage display involves the expression of selected proteins on the surface of
filamentous phage through fusion with phage coat protein, with the genetic
sequence packaged within, linking phenotype to genotype selection. When combined
with antibody libraries, phage display allows for rapid in vitro selection of
antigen-specific antibodies and recovery of their corresponding coding sequence.
Large non-immune and synthetic human libraries have been constructed as well as
smaller immune libraries based on capturing a single individual's immune
repertoire. This completely in vitro process allows for isolation of antibodies
against poorly immunogenic targets as well as those that cannot be obtained by
animal immunization, thus further expanding the utility of the approach. Phage
antibody display represents the first developed methodology for high throughput
screening for human therapeutic antibody candidates. Recently, other methods have
been developed for generation of fully human therapeutic antibodies, such as
single B-cell screening, next-generation genome sequencing and transgenic mice
with human germline B-cell genes. While each of these have their particular
advantages, phage display has remained a key methodology for human antibody
discovery due its in vitro process. Here, we review the continuing role of this
technique alongside other developing technologies for therapeutic antibody
discovery.
PMID- 25135892
TI - Solution to the challenging part of the Shamrock method during lumbar plexus
block.
PMID- 25135891
TI - Emergence agitation: is there a European consensus?
PMID- 25135893
TI - Cut tracheal tube and GlideRite Rigid Stylet.
PMID- 25135894
TI - Does adding milk to tea delay gastric emptying?
PMID- 25135895
TI - (Bright) future of dynamic parameters is in the operating theatre.
PMID- 25135896
TI - Dynamic parameters in the operating theatre: brightness goes with shadows.
PMID- 25135897
TI - Making bisoprolol a perioperative agent.
PMID- 25135898
TI - Benefits of continuous capnography monitoring for intensive care patients
significantly outweigh any risks.
PMID- 25135899
TI - Doses and effects of levobupivacaine and bupivacaine for spinal anaesthesia.
PMID- 25135900
TI - The (Correct) use of capnography will reduce airway complications in intensive
care.
PMID- 25135907
TI - Data protection and epidemiological research: a new EU regulation is in the
pipeline.
PMID- 25135909
TI - Quantitative effect of natural killer-cell licensing on hepatocellular carcinoma
recurrence after curative hepatectomy.
AB - Natural killer (NK) cells have a potential role in immune surveillance of
hepatocellular carcinoma (HCC). Self-recognition of human leukocyte antigens
(HLA) through killer immunoglobulin-like receptors (KIR) confers competence to NK
cells-a process termed "licensing." We investigated the effect of NK-cell
licensing on the susceptibility of patients to HCC recurrence. A total of 170
Japanese patients with HCC who underwent primary curative hepatectomy between
1996 and 2010 were enrolled in this study. The median follow-up period was 5.4
years. We analyzed their KIR-HLA genotypes with sequence-specific polymorphism
based typing and estimated their susceptibility to HCC recurrence by performing
propensity score-matching analyses. The presence of KIR2DL1-C2, KIR2DL2-C1,
KIR3DL1-BW4, or KIR3DL2-A3/11, functional compound genotypes that intrinsically
license NK cells, did not markedly affect HCC recurrence. However, the
multiplicity of those compound KIR-HLA genotypes was significantly associated
with the HCC recurrence rate, i.e., the cumulative risk of recurrence in patients
with at least three compound genotypes was significantly lower than that in
patients with one or two compound genotypes, suggesting that the effect of NK
cell licensing on HCC recurrence is quantitative. Patients at high risk of HCC
recurrence after curative hepatectomy could be identified by KIR-HLA genotyping.
PMID- 25135910
TI - How well informed is the informed consent for cancer clinical trials?
AB - AIMS: The purpose of this study was to analyze the content of informed consent
forms for clinical trials in medical oncology to assess readability, determine
their completeness, and identify any shortcomings. METHODS: Informed consent
forms for Phase I-III studies that were conducted at two tertiary care cancer
centers over a 3-year period were reviewed. Information pertaining to length of
the informed consent form, research regimen/methods, treatment agent, potential
risks, and benefits was extracted. The reading level was assessed by Flesch
Kincaid and Gunning-Fog index readability tests. RESULTS: All of the 112 informed
consent forms clearly stated the voluntary nature of participation. Nearly one
half of the forms (51.8%) were of Phase I studies. The median length of informed
consent form was 20 pages (range: 8-28). A detailed estimation of the frequency
or intensity of risks (range: 3-8 pages) was provided. The average reading level
of the informed consent forms was high (Flesch-Kincaid Grade Level of 9.8), which
corresponds roughly to 10th-grade reading level. Less than 15% of all consent
forms were written at the recommended eighth-grade reading level. A substantial
number of forms did not report a potential risk to pregnant/lactating women
(16.9%), mechanism of action of the investigational agent (34.8%), study schema
(77.6%), a possibility of receiving sub-therapeutic dose (37%), or death (12.5%).
Nearly one half of the forms (49.1%) stated clearly that individual participants
may not benefit. CONCLUSION: Overall, these informed consent forms provided a
detailed description of the trials in accordance to international guidelines.
However, there remains room for improvement, particularly in areas of readability
and document length.
PMID- 25135908
TI - Season and outdoor temperature in relation to detection and control of
hypertension in a large rural Chinese population.
AB - BACKGROUND: In many Western populations, blood pressure varies moderately with
season and outdoor temperature. Relatively little is known about effects of
seasonal changes in blood pressure on the detection and control of hypertension
in general populations, especially in low- and middle-income countries. METHODS:
We analysed cross-sectional data of 57 375 (42% men) participants aged 30-79
(mean 52.3) years who were enrolled during 2004-08, as part of the China Kadoorie
Biobank, from a rural county in the south-east costal Zhejiang Province. Analyses
related daily mean outdoor temperature, obtained from local Meteorological
Bureau, to mean systolic (SBP) and diastolic blood pressure (DBP), rate of newly
detected hypertension and, among those with self-reported physician-diagnosed
hypertension, rate of adequate blood pressure control, using multiple linear and
logistic regression models. RESULTS: The overall mean blood pressure was 135.9
mmHg for SBP and 80.5 mmHg for DBP. Daily outdoor temperature ranged between -2.9
and 33.7 degrees C, with July being the hottest month (mean 29.4 degrees C) and
January the coldest (mean 4.0 degrees C). Comparing January (the coldest month)
with July (the warmest), the differences in the adjusted SBP/DBP were 19.2/7.7
mmHg. Each 10 degrees C lower ambient temperature was associated with 6.9/2.9
mmHg higher SBP/DBP,14.1% higher prevalence of newly detected hypertension and,
among those with pre-diagnosed hypertension, 13.0% lower hypertension control
rate. CONCLUSION: In rural China, lower outdoor temperature is strongly
associated with higher mean blood pressure and hypertension prevalence as well as
poorer hypertension control, and should be considered when conducting population
based hypertension surveys and providing treatment for hypertensive patients.
PMID- 25135911
TI - Ocular pulsations due to posttraumatic compromise of the orbital roof.
PMID- 25135912
TI - Spice, pot, and stroke.
PMID- 25135913
TI - Ischemic stroke after use of the synthetic marijuana "spice".
PMID- 25135916
TI - Clinical reasoning: a 42-year-old man who developed blurred vision and dropped
his iPod while jogging.
PMID- 25135917
TI - Teaching NeuroImages: recurrence of a sural intraneural ganglion cyst after sural
nerve resection.
PMID- 25135919
TI - Fix seniors' care first, says CMA president-elect.
PMID- 25135920
TI - Controversy over doctors' right to say "no".
PMID- 25135922
TI - E-cigarette ban proposed in Toronto.
PMID- 25135924
TI - Dextromethorphan abuse.
PMID- 25135921
TI - Assessment and management of resistant hypertension.
PMID- 25135925
TI - Diabetes in an older woman living in a long-term care residence.
PMID- 25135926
TI - Good health requires a healthy mouth: improving the oral health of Canada's
seniors.
PMID- 25135928
TI - Tracking brain injury and disability.
PMID- 25135927
TI - Association of a quality improvement program with neonatal outcomes in extremely
preterm infants: a prospective cohort study.
AB - BACKGROUND: We previously demonstrated improvement in bronchopulmonary dysplasia
and nosocomial infection among preterm infants at 12 neonatal units using the
Evidence-based Practice for Improving Quality (EPIQ). In the current study, we
assessed the association of Canada-wide implementation of EPIQ with mortality and
morbidity among preterm infants less than 29 weeks gestational age. METHODS: This
prospective cohort study included 6026 infants admitted to 25 Canadian units
between 2008 and 2012 (baseline year, n = 1422; year 1, n = 1611; year 2, n =
1508; year 3, n = 1485). Following a 1-year baseline period and 6 months of
training and planning, EPIQ was implemented over 3 years. Our primary outcome was
a composite of neonatal mortality and any of bronchopulmonary dysplasia, severe
neurologic injury, severe retinopathy of prematurity, necrotizing enterocolitis
and nosocomial infection. We compared outcomes for baseline and year 3 using
multivariable analyses. RESULTS: In adjusted analyses comparing baseline with
year 3, the composite outcome (70% v. 65%; adjusted odds ratio [OR] 0.63, 95%
confidence interval [CI] 0.51 to 0.79), severe retinopathy (17% v. 13%; OR 0.60,
95% CI 0.45 to 0.79), necrotizing enterocolitis (10% v. 8%; OR 0.73, 95% CI 0.52
to 0.98) and nosocomial infections (32% v. 24%; OR 0.63, 95% CI 0.48 to 0.82)
were significantly reduced. The composite outcome was lower among infants born at
26 to 28 weeks gestation (62% v. 52%; OR 0.62, 95% CI 0.49 to 0.78) but not among
infants born at less than 26 weeks gestational age (90% v. 88%; OR 0.73, 95% CI
0.44 to 1.20). INTERPRETATION: EPIQ methodology was generalizable within Canada
and was associated with significantly lower likelihood of the composite outcome,
severe retinopathy, necrotizing enterocolitis and nosocomial infections. Infants
born at 26 to 28 weeks gestational age benefited the most.
PMID- 25135929
TI - CMA wants seniors' care on federal agenda.
PMID- 25135930
TI - Heidi McBride: mitochondria are well connected.
PMID- 25135931
TI - A new piece in the kinetochore jigsaw puzzle.
AB - In eukaryotic cell division, the kinetochore mediates chromosome attachment to
spindle microtubules and acts as a scaffold for signaling pathways, ensuring the
accuracy of chromosome segregation. The architecture of the kinetochore underlies
its function in mitosis. In this issue, Hornung et al. (2014. J. Cell Biol.
http://dx.doi.org/201403081) identify an unexpected linkage between the inner and
outer regions of the kinetochore in budding yeast that suggests a new model for
the construction of this interface.
PMID- 25135933
TI - cPKC regulates interphase nuclear size during Xenopus development.
AB - Dramatic changes in cell and nuclear size occur during development and
differentiation, and aberrant nuclear size is associated with many disease
states. However, the mechanisms that regulate nuclear size are largely unknown. A
robust system for investigating nuclear size is early Xenopus laevis development,
during which reductions in nuclear size occur without changes in DNA content. To
identify cellular factors that regulate nuclear size during development, we
developed a novel nuclear resizing assay wherein nuclei assembled in Xenopus egg
extract become smaller in the presence of cytoplasmic interphase extract isolated
from post-gastrula Xenopus embryos. We show that nuclear shrinkage depends on
conventional protein kinase C (cPKC). Increased nuclear cPKC localization and
activity and decreased nuclear association of lamins mediate nuclear size
reductions during development, and manipulating cPKC activity in vivo during
interphase alters nuclear size in the embryo. We propose a model of steady-state
nuclear size regulation whereby nuclear expansion is balanced by an active cPKC
dependent mechanism that reduces nuclear size.
PMID- 25135932
TI - The tubulin code: molecular components, readout mechanisms, and functions.
AB - Microtubules are cytoskeletal filaments that are dynamically assembled from
alpha/beta-tubulin heterodimers. The primary sequence and structure of the
tubulin proteins and, consequently, the properties and architecture of
microtubules are highly conserved in eukaryotes. Despite this conservation,
tubulin is subject to heterogeneity that is generated in two ways: by the
expression of different tubulin isotypes and by posttranslational modifications
(PTMs). Identifying the mechanisms that generate and control tubulin
heterogeneity and how this heterogeneity affects microtubule function are long
standing goals in the field. Recent work on tubulin PTMs has shed light on how
these modifications could contribute to a "tubulin code" that coordinates the
complex functions of microtubules in cells.
PMID- 25135935
TI - Oxidoreductase activity is necessary for N-glycosylation of cysteine-proximal
acceptor sites in glycoproteins.
AB - Stabilization of protein tertiary structure by disulfides can interfere with
glycosylation of acceptor sites (NXT/S) in nascent polypeptides. Here, we show
that MagT1, an ER-localized thioredoxin homologue, is a subunit of the STT3B
isoform of the oligosaccharyltransferase (OST). The lumenally oriented active
site CVVC motif in MagT1 is required for glycosylation of STT3B-dependent
acceptor sites including those that are closely bracketed by disulfides or
contain cysteine as the internal residue (NCT/S). The MagT1- and STT3B-dependent
glycosylation of cysteine-proximal acceptor sites can be reduced by eliminating
cysteine residues. The predominant form of MagT1 in vivo is oxidized, which is
consistent with transient formation of mixed disulfides between MagT1 and a
glycoprotein substrate to facilitate access of STT3B to unmodified acceptor
sites. Cotranslational N-glycosylation by the STT3A isoform of the OST, which
lacks MagT1, allows efficient modification of acceptor sites in cysteine-rich
protein domains before disulfide bond formation. Thus, mammalian cells use two
mechanisms to achieve N-glycosylation of cysteine proximal acceptor sites.
PMID- 25135937
TI - Pre-placement screening for tuberculosis in healthcare workers.
AB - BACKGROUND: Healthcare workers (HCWs) are at occupational risk of contracting and
transmitting tuberculosis (TB). Despite national guidance, the optimal process
for the pre-placement screening of new entrant HCWs for TB in the UK is not
certain, nor the appropriateness of using a one-step interferon gamma release
assay (IGRA) screening programme. AIMS: To assess the potential for an IGRA-only
TB screening programme for new entrant HCWs, and identify cost savings achieved
through this process. METHODS: We conducted a retrospective analysis of IGRA and
tuberculin skin tests (TST) within our occupational health service over a 3-year
period. HCWs with markedly discordant test results (IGRA negative, TST positive)
were followed up to determine whether they developed active TB. We also estimated
the yearly cost savings if the existing two-step process was replaced with an
IGRA-only programme. RESULTS: Totally, 96/1258 (8%) HCWs had positive IGRA
results; 788 TSTs were performed for newly screened IGRA-negative HCWs without
Bacille Calmette-Guerin scars, among which 597 (76%) tested negative (TST <6 mm).
None of the 10 individuals with grossly discordant test results (TST >15 mm)
developed active TB during the study period. We calculated savings of L20,453 if
the two-step process was replaced with an IGRA-only programme. CONCLUSIONS: The
absence of disease progression in individuals with markedly discordant results in
this study suggest that an IGRA-only screening programme for new HCWs in the UK
is feasible, and may be safe although our follow-up period was insufficient. Our
results also suggest that substantial cost savings can be made by using this
programme.
PMID- 25135934
TI - A cooperative mechanism drives budding yeast kinetochore assembly downstream of
CENP-A.
AB - Kinetochores are megadalton-sized protein complexes that mediate chromosome
microtubule interactions in eukaryotes. How kinetochore assembly is triggered
specifically on centromeric chromatin is poorly understood. Here we use
biochemical reconstitution experiments alongside genetic and structural analysis
to delineate the contributions of centromere-associated proteins to kinetochore
assembly in yeast. We show that the conserved kinetochore subunits Ame1(CENP-U)
and Okp1(CENP-Q) form a DNA-binding complex that associates with the microtubule
binding KMN network via a short Mtw1 recruitment motif in the N terminus of Ame1.
Point mutations in the Ame1 motif disrupt kinetochore function by preventing KMN
assembly on chromatin. Ame1-Okp1 directly associates with the centromere protein
C (CENP-C) homologue Mif2 to form a cooperative binding platform for outer
kinetochore assembly. Our results indicate that the key assembly steps, CENP-A
recognition and outer kinetochore recruitment, are executed through different
yeast constitutive centromere-associated network subunits. This two-step
mechanism may protect against inappropriate kinetochore assembly similar to rate
limiting nucleation steps used by cytoskeletal polymers.
PMID- 25135938
TI - A survey of sitting time among UK employees.
AB - BACKGROUND: Sedentary behaviour is a known risk factor for a wide range of
chronic diseases. This major health risk is likely to increase given the
increasingly sedentary nature of work. AIMS: To investigate the prevalence of
sedentary behaviour in a sample of UK working-aged adults, across a range of
employment sectors. METHODS: A cross-sectional survey conducted with
organizations throughout the UK in the education, government administration,
retail, telecommunications and service industry sectors. The questionnaire
examined employee and organizational information, self-reported domain-specific
sitting time, sleep and physical activity. RESULTS: A total of 1141 employees
completed the questionnaire, of which 504 completed all aspects of the Domain
Specific Sitting Time Questionnaire for work day sitting. Work time sitting
accounted for more than half of the total daily sitting time on a work day (54%).
Significantly more time was reported sitting on a work day than time reported
sleeping (P < 0.001). Males spent more time sitting at work and using a personal
computer at home compared with females. Workers in the telecommunications
industry had the highest sitting times. There were significant positive
associations between sitting time and body mass index. CONCLUSIONS: There is a
pressing need for future workplace health interventions to reduce employee
sitting times.
PMID- 25135936
TI - High density and ligand affinity confer ultrasensitive signal detection by a
guanylyl cyclase chemoreceptor.
AB - Guanylyl cyclases (GCs), which synthesize the messenger cyclic guanosine 3',5'
monophosphate, control several sensory functions, such as phototransduction,
chemosensation, and thermosensation, in many species from worms to mammals. The
GC chemoreceptor in sea urchin sperm can decode chemoattractant concentrations
with single-molecule sensitivity. The molecular and cellular underpinnings of
such ultrasensitivity are not known for any eukaryotic chemoreceptor. In this
paper, we show that an exquisitely high density of 3 * 10(5) GC chemoreceptors
and subnanomolar ligand affinity provide a high ligand-capture efficacy and
render sperm perfect absorbers. The GC activity is terminated within 150 ms by
dephosphorylation steps of the receptor, which provides a means for precise
control of the GC lifetime and which reduces "molecule noise." Compared with
other ultrasensitive sensory systems, the 10-fold signal amplification by the GC
receptor is surprisingly low. The hallmarks of this signaling mechanism provide a
blueprint for chemical sensing in small compartments, such as olfactory cilia,
insect antennae, or even synaptic boutons.
PMID- 25135939
TI - Identification of a new stem cell population that generates Drosophila flight
muscles.
AB - How myoblast populations are regulated for the formation of muscles of different
sizes is an essentially unanswered question. The large flight muscles of
Drosophila develop from adult muscle progenitor (AMP) cells set-aside
embryonically. The thoracic segments are all allotted the same small AMP number,
while those associated with the wing-disc proliferate extensively to give rise to
over 2500 myoblasts. An initial amplification occurs through symmetric divisions
and is followed by a switch to asymmetric divisions in which the AMPs self-renew
and generate post-mitotic myoblasts. Notch signaling controls the initial
amplification of AMPs, while the switch to asymmetric division additionally
requires Wingless, which regulates Numb expression in the AMP lineage. In both
cases, the epidermal tissue of the wing imaginal disc acts as a niche expressing
the ligands Serrate and Wingless. The disc-associated AMPs are a novel muscle
stem cell population that orchestrates the early phases of adult flight muscle
development.
PMID- 25135941
TI - ExaBayes: massively parallel bayesian tree inference for the whole-genome era.
AB - Modern sequencing technology now allows biologists to collect the entirety of
molecular evidence for reconstructing evolutionary trees. We introduce a novel,
user-friendly software package engineered for conducting state-of-the-art
Bayesian tree inferences on data sets of arbitrary size. Our software introduces
a nonblocking parallelization of Metropolis-coupled chains, modifications for
efficient analyses of data sets comprising thousands of partitions and memory
saving techniques. We report on first experiences with Bayesian inferences at the
whole-genome level using the SuperMUC supercomputer and simulated data.
PMID- 25135940
TI - mRNA-programmed translation pauses in the targeting of E. coli membrane proteins.
AB - In all living organisms, ribosomes translating membrane proteins are targeted to
membrane translocons early in translation, by the ubiquitous signal recognition
particle (SRP) system. In eukaryotes, the SRP Alu domain arrests translation
elongation of membrane proteins until targeting is complete. Curiously, however,
the Alu domain is lacking in most eubacteria. In this study, by analyzing genome
wide data on translation rates, we identified a potential compensatory mechanism
in E. coli that serves to slow down the translation during membrane protein
targeting. The underlying mechanism is likely programmed into the coding
sequence, where Shine-Dalgarno-like elements trigger elongation pauses at
strategic positions during the early stages of translation. We provide
experimental evidence that slow translation during targeting and improves
membrane protein production fidelity, as it correlates with better folding of
overexpressed membrane proteins. Thus, slow elongation is important for membrane
protein targeting in E. coli, which utilizes mechanisms different from the
eukaryotic one to control the translation speed.
PMID- 25135943
TI - Adaptive functional diversification of lysozyme in insectivorous bats.
AB - The role of gene duplication in generating new genes and novel functions is well
recognized and is exemplified by the digestion-related protein lysozyme. In
ruminants, duplicated chicken-type lysozymes facilitate the degradation of
symbiotic bacteria in the foregut. Chicken-type lysozyme has also been reported
to show chitinase-like activity, yet no study has examined the molecular
evolution of lysozymes in species that specialize on eating insects.
Insectivorous bats number over 900 species, and lysozyme expression in the mouths
of some of these species is associated with the ingestion of insect cuticle,
suggesting a chitinase role. Here, we show that chicken-type lysozyme has
undergone multiple duplication events in a major family of insect-eating bats
(Vespertilionidae) and that new duplicates have undergone molecular adaptation.
Examination of duplicates from two insectivorous bats-Pipistrellus abramus and
Scotophilus kuhlii-indicated that the new copy was highly expressed in the
tongue, whereas the other one was less tissue-specific. Functional assays applied
to pipistrelle lysozymes confirmed that, of the two copies, the tongue duplicate
was more efficient at breaking down glycol chitin, a chitin derivative. These
results suggest that the evolution of lysozymes in vespertilionid bats has likely
been driven in part by natural selection for insectivory.
PMID- 25135944
TI - Independent birth of a novel TRIMCyp in Tupaia belangeri with a divergent
function from its paralog TRIM5.
AB - The origin of novel genes and their evolutionary fates are long-standing
questions in evolutionary biology. These questions become more complicated for
genes conserved across various lineages, such as TRIM5, an antiretroviral
restriction factor and a retrovirus capsid sensor in immune signaling. TRIM5 has
been subjected to numerous pathogenic challenges and undergone dynamic evolution,
making it an excellent example for studying gene diversification. Previous
studies among several species showed that TRIM5 gained genetic and functional
novelty in a lineage-specific manner, either through gene duplication or a
cyclophilin A retrotransposing into the TRIM5 locus, creating the gene fusion
known as TRIM5-Cyclophilin A (TRIMCyp). To date, the general pattern of TRIM5
across the mammalian lineage remains elusive. In this study, we surveyed 36
mammalian genomes to verify a potentially novel TRIM5 pattern that uniquely seems
to have occurred in tree shrews (Tupaia belangeri), and found that both gene
duplication and retrotransposition worked jointly to form a specific
TRIM5/TRIMCyp cluster not found among other mammals. Evolutionary analyses showed
that tree shrew TRIMCyp (tsTRIMCyp) originated independently in comparison with
previously reported TRIMCyps and underwent strong positive selection, whereas no
signal of positive selection was detected for other tree shrew TRIM5 (tsTRIM5)
genes. Functional assay results suggest a functional divergence between tsTRIMCyp
and its closest paralog TRIM5-4, likely reflecting different fates under diverse
evolutionary forces. These findings present a rare example of novel gene
origination resulting from a combination of gene duplication, retrotransposition,
and exon shuffling processes, providing a new paradigm to study genetic
innovations and evolutionary fates of duplicated genes.
PMID- 25135942
TI - Integrating evolutionary and functional tests of adaptive hypotheses: a case
study of altitudinal differentiation in hemoglobin function in an Andean Sparrow,
Zonotrichia capensis.
AB - In air-breathing vertebrates, the physiologically optimal blood-O2 affinity is
jointly determined by the prevailing partial pressure of atmospheric O2, the
efficacy of pulmonary O2 transfer, and internal metabolic demands. Consequently,
genetic variation in the oxygenation properties of hemoglobin (Hb) may be subject
to spatially varying selection in species with broad elevational distributions.
Here we report the results of a combined functional and evolutionary analysis of
Hb polymorphism in the rufous-collared sparrow (Zonotrichia capensis), a species
that is continuously distributed across a steep elevational gradient on the
Pacific slope of the Peruvian Andes. We integrated a population genomic analysis
that included all postnatally expressed Hb genes with functional studies of
naturally occurring Hb variants, as well as recombinant Hb (rHb) mutants that
were engineered through site-directed mutagenesis. We identified three clinally
varying amino acid polymorphisms: Two in the alpha(A)-globin gene, which encodes
the alpha-chain subunits of the major HbA isoform, and one in the alpha(D)-globin
gene, which encodes the alpha-chain subunits of the minor HbD isoform. We then
constructed and experimentally tested single- and double-mutant rHbs representing
each of the alternative alpha(A)-globin genotypes that predominate at different
elevations. Although the locus-specific patterns of altitudinal differentiation
suggested a history of spatially varying selection acting on Hb polymorphism, the
experimental tests demonstrated that the observed amino acid mutations have no
discernible effect on respiratory properties of the HbA or HbD isoforms. These
results highlight the importance of experimentally validating the hypothesized
effects of genetic changes in protein function to avoid the pitfalls of adaptive
storytelling.
PMID- 25135945
TI - Detecting recent positive selection with high accuracy and reliability by
conditional coalescent tree.
AB - Studies of natural selection, followed by functional validation, are shedding
light on understanding of genetic mechanisms underlying human evolution and
adaptation. Classic methods for detecting selection, such as the integrated
haplotype score (iHS) and Fay and Wu's H statistic, are useful for candidate gene
searching underlying positive selection. These methods, however, have limited
capability to localize causal variants in selection target regions. In this
study, we developed a novel method based on conditional coalescent tree to detect
recent positive selection by counting unbalanced mutations on coalescent gene
genealogies. Extensive simulation studies revealed that our method is more robust
than many other approaches against biases due to various demographic effects,
including population bottleneck, expansion, or stratification, while not
sacrificing its power. Furthermore, our method demonstrated its superiority in
localizing causal variants from massive linked genetic variants. The rate of
successful localization was about 20-40% higher than that of other state-of-the
art methods on simulated data sets. On empirical data, validated functional
causal variants of four well-known positive selected genes were all successfully
localized by our method, such as ADH1B, MCM6, APOL1, and HBB. Finally, the
computational efficiency of this new method was much higher than that of iHS
implementations, that is, 24-66 times faster than the REHH package, and more than
10,000 times faster than the original iHS implementation. These magnitudes make
our method suitable for applying on large sequencing data sets. Software can be
downloaded from https://github.com/wavefancy/scct.
PMID- 25135946
TI - Evidence for a gene involved in multiple and diverse rearrangements in the
Drosophila genus.
AB - In Drosophila, chromosomes have been extensively reorganized during evolution,
with most rearrangements affecting the gene order in chromosomal elements but not
their gene content. The level of reorganization and the evidence for breakpoint
reuse vary both between and within elements. The subito gene stands out as a gene
involved in multiple rearrangements both because of its active single-gene
transposition and because it is the nearest gene to diverse rearrangements
breakpoints. Indeed, subito has undergone three single-gene transpositions and it
is the nearest gene to the breakpoints of other single-gene transpositions and of
two chromosomal inversions. Given that subito is involved in meiosis and
therefore active in the female germ line, the high number of nearby fixed
breakages might be related among others to the presumed high accessibility of the
subito region to the machinery associated with double-strand breaks repair. A
second important contributor would be the reduced and simple regulatory region of
subito, which would imply that a fraction of the rearrangements originating from
subito nearby breakages would have not affected either its pattern or timing of
expression and would have, thus, not resulted in reduced fitness.
PMID- 25135947
TI - Crossing-over in a hypervariable species preferentially occurs in regions of high
local similarity.
AB - Recombination between double-stranded DNA molecules is a key genetic process
which occurs in a wide variety of organisms. Usually, crossing-over (CO) occurs
during meiosis between genotypes with 98.0-99.9% sequence identity, because
within-population nucleotide diversity only rarely exceeds 2%. However, some
species are hypervariable and it is unclear how CO can occur between genotypes
with less than 90% sequence identity. Here, we study CO in Schizophyllum commune,
a hypervariable cosmopolitan basidiomycete mushroom, a frequently encountered
decayer of woody substrates. We crossed two haploid individuals, from the United
States and from Russia, and obtained genome sequences for their 17 offspring. The
average genetic distance between the parents was 14%, making it possible to study
CO at very high resolution. We found reduced levels of linkage disequilibrium
between loci flanking the CO sites indicating that they are mostly confined to
hotspots of recombination. Furthermore, CO events preferentially occurred in
regions under stronger negative selection, in particular within exons that showed
reduced levels of nucleotide diversity. Apparently, in hypervariable species CO
must avoid regions of higher divergence between the recombining genomes due to
limitations imposed by the mismatch repair system, with regions under strong
negative selection providing the opportunity for recombination. These patterns
are opposite to those observed in a number of less variable species indicating
that population genomics of hypervariable species may reveal novel biological
phenomena.
PMID- 25135949
TI - Eukaryotic penelope-like retroelements encode hammerhead ribozyme motifs.
AB - Small self-cleaving RNAs, such as the paradigmatic Hammerhead ribozyme (HHR),
have been recently found widespread in DNA genomes across all kingdoms of life.
In this work, we found that new HHR variants are preserved in the ancient family
of Penelope-like elements (PLEs), a group of eukaryotic retrotransposons regarded
as exceptional for encoding telomerase-like retrotranscriptases and spliceosomal
introns. Our bioinformatic analysis revealed not only the presence of minimalist
HHRs in the two flanking repeats of PLEs but also their massive and widespread
occurrence in metazoan genomes. The architecture of these ribozymes indicates
that they may work as dimers, although their low self-cleavage activity in vitro
suggests the requirement of other factors in vivo. In plants, however, PLEs show
canonical HHRs, whereas fungi and protist PLEs encode ribozyme variants with a
stable active conformation as monomers. Overall, our data confirm the connection
of self-cleaving RNAs with eukaryotic retroelements and unveil these motifs as a
significant fraction of the encoded information in eukaryotic genomes.
PMID- 25135950
TI - Importance of carcinoma-associated fibroblast-derived proteins in clinical
oncology.
AB - Carcinoma-associated fibroblast (CAF) as prominent cell type of the tumour
microenvironment has complex interaction with both the cancer cells and other non
neoplastic surrounding cells. The CAF-derived regulators and extracellular matrix
proteins can support cancer progression by providing a protective
microenvironment for the cancer cells via reduction of chemotherapy sensitivity.
On the other hand, these proteins may act as powerful prognostic markers as well
as potential targets of anticancer therapy. In this review, we summarise the
clinical importance of the major CAF-derived signals influencing tumour behaviour
and determining the outcome of chemotherapy.
PMID- 25135948
TI - Parallel evolution of tetrodotoxin resistance in three voltage-gated sodium
channel genes in the garter snake Thamnophis sirtalis.
AB - Members of a gene family expressed in a single species often experience common
selection pressures. Consequently, the molecular basis of complex adaptations may
be expected to involve parallel evolutionary changes in multiple paralogs. Here,
we use bacterial artificial chromosome library scans to investigate the evolution
of the voltage-gated sodium channel (Nav) family in the garter snake Thamnophis
sirtalis, a predator of highly toxic Taricha newts. Newts possess tetrodotoxin
(TTX), which blocks Nav's, arresting action potentials in nerves and muscle. Some
Thamnophis populations have evolved resistance to extremely high levels of TTX.
Previous work has identified amino acid sites in the skeletal muscle sodium
channel Nav1.4 that confer resistance to TTX and vary across populations. We
identify parallel evolution of TTX resistance in two additional Nav paralogs,
Nav1.6 and 1.7, which are known to be expressed in the peripheral nervous system
and should thus be exposed to ingested TTX. Each paralog contains at least one
TTX-resistant substitution identical to a substitution previously identified in
Nav1.4. These sites are fixed across populations, suggesting that the resistant
peripheral nerves antedate resistant muscle. In contrast, three sodium channels
expressed solely in the central nervous system (Nav1.1-1.3) showed no evidence of
TTX resistance, consistent with protection from toxins by the blood-brain
barrier. We also report the exon-intron structure of six Nav paralogs, the first
such analysis for snake genes. Our results demonstrate that the molecular basis
of adaptation may be both repeatable across members of a gene family and
predictable based on functional considerations.
PMID- 25135952
TI - The most important application of science: As scientists have to justify research
funding with potential social benefits, they may well add education to the list.
PMID- 25135951
TI - Taking control over intracellular fatty acid levels is essential for the analysis
of thermogenic function in cultured primary brown and brite/beige adipocytes.
AB - Thermogenesis in brown adipocytes, conferred by mitochondrial uncoupling protein
1 (UCP1), is receiving great attention because metabolically active brown adipose
tissue may protect humans from metabolic diseases. In particular, the thermogenic
function of brown-like adipocytes in white adipose tissue, known as brite (or
beige) adipocytes, is currently of prime interest. A valid procedure to quantify
the specific contribution of UCP1 to thermogenesis is thus of vital importance.
Adrenergic stimulation of lipolysis is a common way to activate UCP1. We here
report, however, that in this frequently applied setup, taking control over
intracellular fatty acid levels is essential for the analysis of thermogenic
function in cultured brown and brite adipocytes. By the application of these
findings, we demonstrate that UCP1 is functionally thermogenic in intact brite
adipocytes and adrenergic UCP1 activation is largely dependent on adipose
triglyceride lipase (ATGL) rather than hormone sensitive lipase (HSL).
PMID- 25135954
TI - Has enough evidence accumulated to consider CPAP a first-line standard of care in
developing countries?
PMID- 25135953
TI - Is the role as gatekeeper still feasible? A survey among Dutch general
practitioners.
AB - INTRODUCTION: In the 2012 International Health Policy Survey by the Commonwealth
Fund, 57% of Dutch GPs indicated that Dutch patients receive too much health
care. This is an unexpected finding, given the clear gatekeeper role of Dutch GPs
and recent efforts strengthening this role. OBJECTIVES: The study aims to explore
where perceived overuse of care prevails and to identify factors associated with
too much care at the entry point of Dutch health care. METHOD: An American survey
exploring perceptions of the amount of care among primary care providers was
modified for relevance to the Dutch health system. We further included additional
factors possibly related to overuse based on 12 interviews with Dutch GPs. The
survey was sent to a random sample of 600 GPs. RESULTS: Dutch GPs (N = 157;
response rate 26.2%) indicated that patients receive (much) too much care in
general hospitals, primary care, GP cooperatives as well as private clinics. The
Dutch responding GPs showed a relatively demand-satisfying attitude, which
contributed to the delivery of too much care, often leading to deviation from
guidelines and professional norms. The increasing availability of diagnostic
facilities was identified as an additional factor contributing to the provision
of unnecessary care. Finally, funding gaps between primary care and hospitals
impede cooperation and coordination, provoking unnecessary care. CONCLUSION: Our
results--most notably regarding the demand-satisfying attitude of responding GPs-
call into question the classical view of the guidance and gatekeeper role of GPs
in the Dutch health care system.
PMID- 25135955
TI - Prematurity and programming of cardiovascular disease risk: a future challenge
for public health?
AB - There is substantial epidemiological evidence linking low birth weight with adult
cardiometabolic disease risk factors. This has led to the concept of 'early life
programming' or the 'developmental origins of disease' which proposes that
exposure to adverse conditions during critical stages of early development
results in compensatory mechanisms predicted to aid survival. There is growing
evidence that preterm infants, many of whom are of low birth weight, are also at
increased risk of adult cardiometabolic disease. In this article, we provide a
broad overview of the evidence linking preterm birth and cardiovascular disease
risk and discuss potential consequences for public health.
PMID- 25135956
TI - H3S28 phosphorylation is a hallmark of the transcriptional response to cellular
stress.
AB - The selectivity of transcriptional responses to extracellular cues is reflected
by the deposition of stimulus-specific chromatin marks. Although histone H3
phosphorylation is a target of numerous signaling pathways, its role in
transcriptional regulation remains poorly understood. Here, for the first time,
we report a genome-wide analysis of H3S28 phosphorylation in a mammalian system
in the context of stress signaling. We found that this mark targets as many as
50% of all stress-induced genes, underlining its importance in signal-induced
transcription. By combining ChIP-seq, RNA-seq, and mass spectrometry we
identified the factors involved in the biological interpretation of this histone
modification. We found that MSK1/2-mediated phosphorylation of H3S28 at stress
responsive promoters contributes to the dissociation of HDAC corepressor
complexes and thereby to enhanced local histone acetylation and subsequent
transcriptional activation of stress-induced genes. Our data reveal a novel
function of the H3S28ph mark in the activation of mammalian genes in response to
MAP kinase pathway activation.
PMID- 25135959
TI - Innovative practice editorial.
PMID- 25135957
TI - The landscape of human STR variation.
AB - Short tandem repeats are among the most polymorphic loci in the human genome.
These loci play a role in the etiology of a range of genetic diseases and have
been frequently utilized in forensics, population genetics, and genetic
genealogy. Despite this plethora of applications, little is known about the
variation of most STRs in the human population. Here, we report the largest-scale
analysis of human STR variation to date. We collected information for nearly
700,000 STR loci across more than 1000 individuals in Phase 1 of the 1000 Genomes
Project. Extensive quality controls show that reliable allelic spectra can be
obtained for close to 90% of the STR loci in the genome. We utilize this call set
to analyze determinants of STR variation, assess the human reference genome's
representation of STR alleles, find STR loci with common loss-of-function
alleles, and obtain initial estimates of the linkage disequilibrium between STRs
and common SNPs. Overall, these analyses further elucidate the scale of genetic
variation beyond classical point mutations.
PMID- 25135958
TI - RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript
in secondary glioblastomas.
AB - Studies of gene rearrangements and the consequent oncogenic fusion proteins have
laid the foundation for targeted cancer therapy. To identify oncogenic fusions
associated with glioma progression, we catalogued fusion transcripts by RNA-seq
of 272 gliomas. Fusion transcripts were more frequently found in high-grade
gliomas, in the classical subtype of gliomas, and in gliomas treated with
radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified,
including three recurrent fusion transcripts: FGFR3-TACC3, RNF213-SLC26A11, and
PTPRZ1-MET (ZM). Interestingly, the ZM fusion was found only in grade III
astrocytomas (1/13; 7.7%) or secondary GBMs (sGBMs, 3/20; 15.0%). In an
independent cohort of sGBMs, the ZM fusion was found in three of 20 (15%)
specimens. Genomic analysis revealed that the fusion arose from translocation
events involving introns 3 or 8 of PTPRZ and intron 1 of MET. ZM fusion
transcripts were found in GBMs irrespective of isocitrate dehydrogenase 1 (IDH1)
mutation status. sGBMs harboring ZM fusion showed higher expression of genes
required for PIK3CA signaling and lowered expression of genes that suppressed RB1
or TP53 function. Expression of the ZM fusion was mutually exclusive with EGFR
overexpression in sGBMs. Exogenous expression of the ZM fusion in the U87MG
glioblastoma line enhanced cell migration and invasion. Clinically, patients
afflicted with ZM fusion harboring glioblastomas survived poorly relative to
those afflicted with non-ZM-harboring sGBMs (P < 0.001). Our study profiles the
shifting RNA landscape of gliomas during progression and reveled ZM as a novel,
recurrent fusion transcript in sGBMs.
PMID- 25135962
TI - Introduction.
PMID- 25135963
TI - Analysis of the RNA content of the exosomes derived from blood serum and urine
and its potential as biomarkers.
AB - Exosomes are tiny vesicles (30-150 nm) constantly secreted by all healthy and
abnormal cells, and found in abundance in all body fluids. These vesicles, loaded
with unique RNA and protein cargo, have a wide range of biological functions,
including cell-to-cell communication and signalling. As such, exosomes hold
tremendous potential as biomarkers and could lead to the development of minimally
invasive diagnostics and next generation therapies within the next few years.
Here, we describe the strategies for isolation of exosomes from human blood serum
and urine, characterization of their RNA cargo by sequencing, and present the
initial data on exosome labelling and uptake tracing in a cell culture model. The
value of exosomes for clinical applications is discussed with an emphasis on
their potential for diagnosing and treating neurodegenerative diseases and brain
cancer.
PMID- 25135964
TI - Exosome platform for diagnosis and monitoring of traumatic brain injury.
AB - We have previously demonstrated the release of membranous structures by cells
into their extracellular environment, which are termed exosomes, microvesicles or
extracellular vesicles depending on specific characteristics, including size,
composition and biogenesis pathway. With activation, injury, stress,
transformation or infection, cells express proteins and RNAs associated with the
cellular responses to these events. The exosomes released by these cells can
exhibit an array of proteins, lipids and nucleic acids linked to these
physiologic events. This review focuses on exosomes associated with traumatic
brain injury, which may be both diagnostic and a causative factor in the
progression of the injury. Based on current data, exosomes play essential roles
as conveyers of intercellular communication and mediators of many of the
pathological conditions associated with development, progression and therapeutic
failures and cellular stress in a variety of pathologic conditions. These
extracellular vesicles express components responsible for angiogenesis promotion,
stromal remodelling, signal pathway activation through growth factor/receptor
transfer, chemoresistance, immunologic activation and genetic exchange. These
circulating exosomes not only represent a central mediator of the pro
inflammatory microenvironment linked with secondary brain injury, but their
presence in the peripheral circulation may serve as a surrogate for biopsies,
enabling real-time diagnosis and monitoring of neurodegenerative progression.
PMID- 25135966
TI - Extracellular-vesicle type of volume transmission and tunnelling-nanotube type of
wiring transmission add a new dimension to brain neuro-glial networks.
AB - Two major types of intercellular communication are found in the central nervous
system (CNS), namely wiring transmission (WT; point-to-point communication via
private channels, e.g. synaptic transmission) and volume transmission (VT;
communication in the extracellular fluid and in the cerebrospinal fluid). Volume
and synaptic transmission become integrated because their chemical signals
activate different types of interacting receptors in heteroreceptor complexes
located synaptically and extrasynaptically in the plasma membrane. In VT, we
focus on the role of the extracellular-vesicle type of VT, and in WT, on the
potential role of the tunnelling-nanotube (TNT) type of WT. The so-called
exosomes appear to be the major vesicular carrier for intercellular communication
but the larger microvesicles also participate. Extracellular vesicles are
released from cultured cortical neurons and different types of glial cells and
modulate the signalling of the neuronal-glial networks of the CNS. This type of
VT has pathological relevance, and epigenetic mechanisms may participate in the
modulation of extracellular-vesicle-mediated VT. Gerdes and co-workers proposed
the existence of a novel type of WT based on TNTs, which are straight
transcellular channels leading to the formation in vitro of syncytial cellular
networks found also in neuronal and glial cultures.
PMID- 25135965
TI - The RNA-centred view of the synapse: non-coding RNAs and synaptic plasticity.
AB - If mRNAs were the only RNAs made by a neuron, there would be a simple mapping of
mRNAs to proteins. However, microRNAs and other non-coding RNAs (ncRNAs; endo
siRNAs, piRNAs, BC1, BC200, antisense and long ncRNAs, repeat-related
transcripts, etc.) regulate mRNAs via effects on protein translation as well as
transcriptional and epigenetic mechanisms. Not only are genes ON or OFF, but
their ability to be translated can be turned ON or OFF at the level of synapses,
supporting an enormous increase in information capacity. Here, I review evidence
that ncRNAs are expressed pervasively within dendrites in mammalian brain; that
some are activity-dependent and highly enriched near synapses; and that synaptic
ncRNAs participate in plasticity responses including learning and memory.
Ultimately, ncRNAs can be viewed as the post-it notes of the neuron. They have no
literal meaning of their own, but derive their functions from where (and to what)
they are stuck. This may explain, in part, why ncRNAs differ so dramatically from
protein-coding genes, both in terms of the usual indicators of functionality and
in terms of evolutionary constraints. ncRNAs do not appear to be direct mediators
of synaptic transmission in the manner of neurotransmitters or receptors, yet
they orchestrate synaptic plasticity-and may drive species-specific changes in
cognition.
PMID- 25135967
TI - An evolving view of epigenetic complexity in the brain.
AB - Recent scientific advances have revolutionized our understanding of classical
epigenetic mechanisms and the broader landscape of molecular interactions and
cellular functions that are inextricably linked to these processes. Our current
view of epigenetics includes an increasing appreciation for the dynamic nature of
DNA methylation, active mechanisms for DNA demethylation, differential functions
of 5-methylcytosine and its oxidized derivatives, the intricate regulatory logic
of histone post-translational modifications, the incorporation of histone
variants into chromatin, nucleosome occupancy and dynamics, and direct links
between cellular signalling pathways and the actions of chromatin 'reader',
'writer' and 'eraser' molecules. We also have an increasing awareness of the
seemingly ubiquitous roles played by diverse classes of selectively expressed non
coding RNAs in transcriptional, post-transcriptional, post-translational and
local and higher order chromatin modulatory processes. These perspectives are
still evolving with novel insights continuing to emerge rapidly (e.g. those
related to epigenetic regulation of mobile genetic elements, epigenetic
mechanisms in mitochondria, roles in nuclear architecture and 'RNA epigenetics').
The precise functions of these epigenetic factors/phenomena are largely unknown.
However, it is unequivocal that they serve as key mediators of brain complexity
and flexibility, including neural development and aging, cellular
differentiation, homeostasis, stress responses, and synaptic and neural network
connectivity and plasticity.
PMID- 25135969
TI - Long-term climbing fibre activity induces transcription of microRNAs in
cerebellar Purkinje cells.
AB - Synaptic activation of central neurons is often evoked by electrical stimulation
leading to post-tetanic potentiation, long-term potentiation or long-term
depression. Even a brief electrical tetanus can induce changes in as many as 100
proteins. Since climbing fibre activity is often associated with cerebellar
behavioural plasticity, we used horizontal optokinetic stimulation (HOKS) to
naturally increase synaptic input to floccular Purkinje cells in mice for hours,
not minutes, and investigated how this activity influenced the transcription of
microRNAs, small non-coding nucleotides that reduce transcripts of multiple,
complementary mRNAs. A single microRNA can reduce the translation of as many as
30 proteins. HOKS evoked increases in 12 microRNA transcripts in floccular
Purkinje cells. One of these microRNAs, miR335, increased 18-fold after 24 h of
HOKS. After HOKS stopped, miR335 transcripts decayed with a time constant of
approximately 2.5 h. HOKS evoked a 28-fold increase in pri-miR335 transcripts
compared with an 18-fold increase in mature miR335 transcripts, confirming that
climbing fibre-evoked increases in miR335 could be attributed to increases in
transcription. We used three screens to identify potential mRNA targets for
miR335 transcripts: (i) nucleotide complementarity, (ii) detection of increased
mRNAs following microinjection of miR335 inhibitors into the cerebellum, and
(iii) detection of decreased mRNAs following HOKS. Two genes, calbindin and 14-3
3-theta, passed these screens. Transfection of N2a cells with miR335 inhibitors
or precursors inversely regulated 14-3-3-theta transcripts. Immunoprecipitation
of 14-3-3-theta co-immunoprecipitated PKC-gamma and GABAAgamma2. Knockdown of
either 14-3-3-theta or PKC-gamma decreased the serine phosphorylation of
GABAAgamma2, suggesting that 14-3-3-theta and PKC-gamma under the control of
miR335 homeostatically regulate the phosphorylation and insertion of GABAAgamma2
into the Purkinje cell post-synaptic membrane.
PMID- 25135968
TI - The role of long non-coding RNAs in neurodevelopment, brain function and
neurological disease.
AB - Long non-coding RNAs (lncRNAs) are transcripts with low protein-coding potential
that represent a large proportion of the transcriptional output of the cell. Many
lncRNAs exhibit features indicative of functionality including tissue-restricted
expression, localization to distinct subcellular structures, regulated expression
and evolutionary conservation. Some lncRNAs have been shown to associate with
chromatin-modifying activities and transcription factors, suggesting that a
common mode of action may be to guide protein complexes to target genomic loci.
However, the functions (if any) of the vast majority of lncRNA transcripts are
currently unknown, and the subject of investigation. Here, we consider the
putative role(s) of lncRNAs in neurodevelopment and brain function with an
emphasis on the epigenetic regulation of gene expression. Associations of lncRNAs
with neurodevelopmental/neuropsychiatric disorders, neurodegeneration and brain
cancers are also discussed.
PMID- 25135970
TI - Systematic identification of 3'-UTR regulatory elements in activity-dependent
mRNA stability in hippocampal neurons.
AB - Ongoing neuronal activity during development and plasticity acts to refine
synaptic connections and contributes to the induction of plasticity and
ultimately long-term memory storage. Activity-dependent, post-transcriptional
control of mRNAs occurs through transport to axonal and dendritic compartments,
local translation and mRNA stability. We have identified a mechanism that
contributes to activity-dependent regulation of mRNA stability during synaptic
plasticity in rat hippocampal neurons. In this study, we demonstrate rapid, post
transcriptional control over process-enriched mRNAs by neuronal activity.
Systematic analysis of the 3'-UTRs of destabilized transcripts, identifies
enrichment in sequence motifs corresponding to microRNA (miRNA)-binding sites.
The miRNAs that were identified, miR-326-3p/miR-330-5p, miR-485-5p, miR-666-3p
and miR-761 are predicted to regulate networks of genes important in plasticity
and development. We find that these miRNAs are developmentally regulated in the
hippocampus, many increasing by postnatal day 14. We further find that miR-485-5p
controls NGF-induced neurite outgrowth in PC12 cells, tau expression and axonal
development in hippocampal neurons. miRNAs can function at the synapse to rapidly
control and affect short- and long-term changes at the synapse. These processes
likely occur during refinement of synaptic connections and contribute to the
induction of plasticity and learning and memory.
PMID- 25135971
TI - Multifaceted effects of oligodendroglial exosomes on neurons: impact on neuronal
firing rate, signal transduction and gene regulation.
AB - Exosomes are small membranous vesicles of endocytic origin that are released by
almost every cell type. They exert versatile functions in intercellular
communication important for many physiological and pathological processes.
Recently, exosomes attracted interest with regard to their role in cell-cell
communication in the nervous system. We have shown that exosomes released from
oligodendrocytes upon stimulation with the neurotransmitter glutamate are
internalized by neurons and enhance the neuronal stress tolerance. Here, we
demonstrate that oligodendroglial exosomes also promote neuronal survival during
oxygen-glucose deprivation, a model of cerebral ischaemia. We show the transfer
from oligodendrocytes to neurons of superoxide dismutase and catalase, enzymes
which are known to help cells to resist oxidative stress. Additionally, we
identify various effects of oligodendroglial exosomes on neuronal physiology.
Electrophysiological analysis using in vitro multi-electrode arrays revealed an
increased firing rate of neurons exposed to oligodendroglial exosomes. Moreover,
gene expression analysis and phosphorylation arrays uncovered differentially
expressed genes and altered signal transduction pathways in neurons after exosome
treatment. Our study thus provides new insight into the broad spectrum of action
of oligodendroglial exosomes and their effects on neuronal physiology. The
exchange of extracellular vesicles between neural cells may exhibit remarkable
potential to impact brain performance.
PMID- 25135972
TI - Epigenetic setting and reprogramming for neural cell fate determination and
differentiation.
AB - In the mammalian brain, epigenetic mechanisms are clearly involved in the
regulation of self-renewal of neural stem cells and the derivation of their
descendants, i.e. neurons, astrocytes and oligodendrocytes, according to the
developmental timing and the microenvironment, the 'niche'. Interestingly, local
epigenetic changes occur, concomitantly with genome-wide level changes, at a set
of gene promoter regions for either down- or upregulation of the gene. In
addition, intergenic regions also sensitize the availability of epigenetic
modifiers, which affects gene expression through a relatively long-range
chromatinic interaction with the transcription regulatory machineries including
non-coding RNA (ncRNA) such as promoter-associated ncRNA and enhancer ncRNA. We
show that such an epigenetic landscape in a neural cell is statically but
flexibly formed together with a variable combination of generally and locally
acting nuclear molecules including master transcription factors and cell-cycle
regulators. We also discuss the possibility that revealing the epigenetic
regulation by the local DNA-RNA-protein assemblies would promote methodological
innovations, e.g. neural cell reprogramming, engineering and transplantation, to
manipulate neuronal and glial cell fates for the purpose of medical use of these
cells.
PMID- 25135973
TI - DNA modifications in the mammalian brain.
AB - DNA methylation is a crucial epigenetic mark in mammalian development, genomic
imprinting, X-inactivation, chromosomal stability and suppressing parasitic DNA
elements. DNA methylation in neurons has also been suggested to play important
roles for mammalian neuronal functions, and learning and memory. In this review,
we first summarize recent discoveries and fundamental principles of DNA
modifications in the general epigenetics field. We then describe the profiles of
different DNA modifications in the mammalian brain genome. Finally, we discuss
roles of DNA modifications in mammalian brain development and function.
PMID- 25135974
TI - The methylated-DNA binding protein MBD2 enhances NGFI-A (egr-1)-mediated
transcriptional activation of the glucocorticoid receptor.
AB - Variations in maternal care in the rat influence the epigenetic state and
transcriptional activity of glucocorticoid receptor (GR) gene in the hippocampus.
The mechanisms underlying this maternal effect remained to be defined, including
the nature of the relevant maternally regulated intracellular signalling
pathways. We show here that increased maternal licking/grooming (LG), which
stably enhances hippocampal GR expression, paradoxically increases hippocampal
expression of the methyl-CpG binding domain protein-2 (MBD2) and MBD2 binding to
the exon 17 GR promoter. Knockdown experiments of MBD2 in hippocampal primary
cell culture show that MBD2 is required for activation of exon 17 GR promoter.
Ectopic co-expression of nerve growth factor-inducible protein A (NGFI-A) with
MBD2 in HEK 293 cells with site-directed mutagenesis of the NGFI-A response
element within the methylated exon 17 GR promoter supports the hypothesis that
MBD2 collaborates with NGFI-A in binding and activation of this promoter. These
data suggest a possible mechanism linking signalling pathways, which are
activated by behavioural stimuli and activation of target genes.
PMID- 25135975
TI - Regulation of histone H3K4 methylation in brain development and disease.
AB - The growing list of mutations implicated in monogenic disorders of the developing
brain includes at least seven genes (ARX, CUL4B, KDM5A, KDM5C, KMT2A, KMT2C,
KMT2D) with loss-of-function mutations affecting proper regulation of histone H3
lysine 4 methylation, a chromatin mark which on a genome-wide scale is broadly
associated with active gene expression, with its mono-, di- and trimethylated
forms differentially enriched at promoter and enhancer and other regulatory
sequences. In addition to these rare genetic syndromes, dysregulated H3K4
methylation could also play a role in the pathophysiology of some cases diagnosed
with autism or schizophrenia, two conditions which on a genome-wide scale are
associated with H3K4 methylation changes at hundreds of loci in a subject
specific manner. Importantly, the reported alterations for some of the diseased
brain specimens included a widespread broadening of H3K4 methylation profiles at
gene promoters, a process that could be regulated by the UpSET(KMT2E/MLL5)
histone deacetylase complex. Furthermore, preclinical studies identified maternal
immune activation, parental care and monoaminergic drugs as environmental
determinants for brain-specific H3K4 methylation. These novel insights into the
epigenetic risk architectures of neurodevelopmental disease will be highly
relevant for efforts aimed at improved prevention and treatment of autism and
psychosis spectrum disorders.
PMID- 25135976
TI - MicroRNAs and synaptic plasticity--a mutual relationship.
AB - MicroRNAs (miRNAs) are rapidly emerging as central regulators of gene expression
in the postnatal mammalian brain. Initial studies mostly focused on the function
of specific miRNAs during the development of neuronal connectivity in culture,
using classical gain- and loss-of-function approaches. More recently, first
examples have documented important roles of miRNAs in plastic processes in intact
neural circuits in the rodent brain related to higher cognitive abilities and
neuropsychiatric disease. At the same time, evidence is accumulating that miRNA
function itself is subjected to sophisticated control mechanisms engaged by the
activity of neural circuits. In this review, we attempt to pay tribute to this
mutual relationship between miRNAs and synaptic plasticity. In particular, in the
first part, we summarize how neuronal activity influences each step in the
lifetime of miRNAs, including the regulation of transcription, maturation, gene
regulatory function and turnover in mammals. In the second part, we discuss
recent examples of miRNA function in synaptic plasticity in rodent models and
their implications for higher cognitive function and neurological disorders, with
a special emphasis on epilepsy as a disorder of abnormal nerve cell activity.
PMID- 25135977
TI - Extracellular vesicles as modulators of cell-to-cell communication in the healthy
and diseased brain.
AB - Homeostasis relies heavily on effective cell-to-cell communication. In the
central nervous system (CNS), probably more so than in other organs, such
communication is crucial to support and protect neurons especially during ageing,
as well as to control inflammation, remove debris and infectious agents. Emerging
evidence indicates that extracellular vesicles (EVs) including endosome-derived
exosomes and fragments of the cellular plasma membrane play a key role in
intercellular communication by transporting messenger RNA, microRNA (miRNA) and
proteins. In neurodegenerative diseases, secreted vesicles not only remove
misfolded proteins, but also transfer aggregated proteins and prions and are thus
thought to perpetuate diseases by 'infecting' neighbouring cells with these
pathogenic proteins. Conversely, in other CNS disorders signals from stressed
cells may help control inflammation and inhibit degeneration. EVs may also
reflect the status of the CNS and are present in the cerebrospinal fluid
indicating that exosomes may act as biomarkers of disease. That extracellular RNA
and in particular miRNA, can be transferred by EV also indicates that these
vesicles could be used as carriers to specifically target the CNS to deliver
immune modulatory drugs, neuroprotective agents and anti-cancer drugs. Here, we
discuss the recent evidence indicating the potential role of exosomes in
neurological disorders and how knowledge of their biology may enable a Trojan
horse approach to deliver drugs into the CNS and treat neurodegenerative and
other disorders of the CNS.
PMID- 25135978
TI - MicroRNA-8 promotes robust motor axon targeting by coordinate regulation of cell
adhesion molecules during synapse development.
AB - Neuronal connectivity and specificity rely upon precise coordinated deployment of
multiple cell-surface and secreted molecules. MicroRNAs have tremendous potential
for shaping neural circuitry by fine-tuning the spatio-temporal expression of key
synaptic effector molecules. The highly conserved microRNA miR-8 is required
during late stages of neuromuscular synapse development in Drosophila. However,
its role in initial synapse formation was previously unknown. Detailed analysis
of synaptogenesis in this system now reveals that miR-8 is required at the
earliest stages of muscle target contact by RP3 motor axons. We find that the
localization of multiple synaptic cell adhesion molecules (CAMs) is dependent on
the expression of miR-8, suggesting that miR-8 regulates the initial assembly of
synaptic sites. Using stable isotope labelling in vivo and comparative mass
spectrometry, we find that miR-8 is required for normal expression of multiple
proteins, including the CAMs Fasciclin III (FasIII) and Neuroglian (Nrg). Genetic
analysis suggests that Nrg and FasIII collaborate downstream of miR-8 to promote
accurate target recognition. Unlike the function of miR-8 at mature larval
neuromuscular junctions, at the embryonic stage we find that miR-8 controls key
effectors on both sides of the synapse. MiR-8 controls multiple stages of synapse
formation through the coordinate regulation of both pre- and postsynaptic cell
adhesion proteins.
PMID- 25135981
TI - Towards evidence based medicine for paediatricians.
PMID- 25135979
TI - Postnatal signalling with homeoprotein transcription factors.
AB - Homeoprotein (HP) transcription factors were originally identified for their
embryonic cell-autonomous developmental functions. In this review, we discuss
their postnatal and adult physiological functions based on the study of Otx2,
Engrailed-1 and Engrailed-2 (collectively Engrailed). For Engrailed, we discuss
its function in the cell-autonomous regulation of ventral midbrain dopaminergic
neuron survival and physiology and in the non-cell-autonomous maintenance of
axons. For Otx2, we describe how the protein is expressed in the choroid plexus
and transported into cortical parvalbumin cells where it regulates plasticity in
the visual cortex. These two examples illustrate how the understanding of HP
postnatal and adult functions, including signalling functions, may lead to the
identification of disease-associated genetic pathways and to the development of
original therapeutic strategies.
PMID- 25135980
TI - The role of epigenetic-related codes in neurocomputation: dynamic hardware in the
brain.
AB - This paper presents a review of recent work on the role that two epigenetic
related systems may play in information processing mechanisms in the brain. The
first consists of exosomes that transport epigenetic-related molecules between
neurons. The second consists of homeoproteins like Otx2 that carry information
from sense organs to primary sensory cortex. There is developing evidence that
presynaptic neurons may be able to modulate the fine microanatomical structure in
the postsynaptic neuron. This may be conducted by three mechanisms, of which the
first is well established and the latter two are novel. (i) By the well
established activation of receptors that trigger a chain of signalling molecules
(second messengers) that result in the upregulation and/or activation of a
transcription factor. The two novel systems are the exosome system and
homeoproteins. (ii) Exosomes are small vesicles that are released upon activation
of the axon terminal, traverse the synaptic cleft, probably via astrocytes and
are taken up by the postsynaptic neuron. They carry a load of signalling proteins
and a variety of forms of RNA. These loads may then be transported widely
throughout the postsynaptic neuron and engineer modulations in the fine structure
of computational machinery by epigenetic-related processes. (iii) Otx2 is a
transcription factor that, inter alia, controls the development and survival of
PV+ GABAergic interneurons (PV cells) in the primary visual cortex. It is
synthesized in the retina and is transported to the cortex by a presently unknown
mechanism that probably includes direct cell-to-cell transfer, and may, or may
not, include transfer by the dynein and exosome systems in addition. These three
mechanisms explain a quantity of data from the field of de- and reafferentation
plasticity. These data show that the modality of the presynaptic neuron controls
to a large extent the modality of the postsynaptic neuron. However, the mechanism
that effects this is currently unknown. The exosome and the homeoprotein
hypotheses provide novel explanations to add to the well-established earlier
mechanism described above.
PMID- 25135983
TI - Outcome of coronary artery bypass grafting in a tertiary-care center in Pakistan.
AB - BACKGROUND: Coronary artery bypass grafting and percutaneous coronary
intervention are revascularization options for significant coronary artery
disease. While international data support the use of coronary artery bypass in
high-risk groups, regional data on outcomes in these groups are rare. We
conducted a retrospective study to determine the outcomes of patients undergoing
coronary artery bypass for left main and multivessel disease. METHODS: Two
thousand eight hundred and fifty-one patients undergoing coronary artery bypass
at the Aga Khan University Hospital from 2006 to 2013 were included; patients
undergoing redo surgery were excluded. Demographic data, comorbidities,
angiography findings, in-hospital complications, one-month and one-year follow-up
were analyzed. RESULTS: Of the 2851 patients, 568 had left main disease (group 1)
and 2283 (group 2) had multivessel disease (>=2 vessels excluding the left main).
Group 1 had significantly more chronic lung disease, cardiogenic shock, and
congestive heart failure than group 2 (p < 0.001); 50.6% of patients were
diabetic and 71.8% were hypertensive. Mortality was 5.1% and 2.2% during hospital
stay, 6.5% and 2.6% at 30 days, and 6.7% and 2.7% at 1 year in groups 1 and 2,
respectively. CONCLUSION: Our comparable results and international data advocate
revision of the current practice of using percutaneous coronary intervention over
coronary artery bypass in the developing world. Institutional results are
essential to determine the outcome of coronary artery bypass in high-risk
populations with a high burden of diabetes and hypertension. We noted increased
complications and mortality in patients with left main rather than multivessel
disease.
PMID- 25135985
TI - Enhancing the objectivity of the Japanese classification of peritoneal metastases
from colorectal cancer.
AB - OBJECTIVE: The Japanese classification of peritoneal metastases from colorectal
cancer is easy to use for general surgeons in routine clinical practice. However,
the objectivity of this classification has not been determined. This study aimed
to clarify the objectivity of the Japanese classification of peritoneal
metastases from colorectal cancer. METHODS: The data of patients with Stage IV
colorectal cancer between 1991 and 2007 in 16 hospitals, who were members of the
Japanese Society for Cancer of the Colon and Rectum, were investigated. The size,
number and extent (nine areas) of peritoneal metastases according to the Japanese
classification (P1, P2 and P3) were investigated using Akaike's information
criterion. RESULTS: Of the 564 colorectal cancer patients with synchronous
peritoneal metastases, 341 had hematogenous metastases. The minimum Akaike's
information criterion was obtained with the cutoff value of one area for P1
metastasis and two or more areas for P2 metastasis (P < 0.0001). When P2
metastasis was compared with P3 metastasis, the cutoff value of the number of
peritoneal metastases was 10. CONCLUSIONS: The present study proposes a revision
that would give objectivity to the present Japanese classification as follows: P1
is defined as peritoneal metastases 20 mm or smaller confined to one area; P2 is
defined as 10 or fewer peritoneal metastases disseminated in two or more areas,
or peritoneal metastases confined to one area but the size is >20 mm and P3 is
defined as >10 peritoneal metastases disseminated in two or more areas.
PMID- 25135984
TI - Circulating tumor cells correlate with recurrence in stage III small-cell lung
cancer after systemic chemoradiotherapy and prophylactic cranial irradiation.
AB - OBJECTIVE: We investigated the correlation between circulating tumor cells and
the incidence of brain metastases as a first site of recurrence among patients
with small-cell lung cancer after systemic chemoradiotherapy and prophylactic
cranial irradiation. In addition, we assessed the contribution of circulating
tumor cells for planning the appropriate total dose of prophylactic cranial
irradiation for small-cell lung cancer. METHODS: Patients (n = 112) with
diagnosed Stage III small-cell lung cancer were treated with four cycles of
platinum-based regimen and concurrent chest irradiation, and then prophylactic
cranial irradiation. Blood samples for circulating tumor cell analysis were
obtained before the initiation of chemotherapy and after the first and fourth
cycle of chemotherapy. RESULTS: Circulating tumor cells after the first cycle of
chemotherapy correlated with tumor response after completion of chemotherapy (P =
0.012). Patients with brain as the first site suffered a higher rate of further
metastases to other organs, and local recurrence, compared with those whose first
site was the other organs (P < 0.001), and their survival rates were worse.
Circulating tumor cells at baseline were the sole independent prognostic factor
for specific progression-free survival. Receiver operating characteristic curves
based on median specific progression-free survival revealed a circulating tumor
cell cutoff at baseline of 218, and circulating tumor cells <=218 at baseline
correlated with significantly higher progression-free survival (P = 0.007),
specific progression-free survival (P = 0.001) and overall survival (P = 0.001).
CONCLUSIONS: Circulating tumor cells prior to the initiation of chemotherapy are
a valuable predictor of specific progression-free survival in Stage III small
cell lung cancer. For patients with circulating tumor cells >218, prophylactic
cranial irradiation at a total dose of 30 Gy in 15 fractions is insufficient.
PMID- 25135987
TI - Delayed bronchobiliary fistula and cholangiolithiasis following percutaneous
radio frequency ablation for hepatocellular carcinoma.
AB - Although percutaneous radio frequency ablation for hepatocellular carcinoma is a
minimally invasive therapy, there are some complications reported; major
complications include hemorrhage (0.477%), hepatic injuries (1.690%), and
extrahepatic organ injuries (0.691%). We, for the first time, described a rare
complication of delayed bronchobiliary fistula and cholangiolithiasis in common
bile duct following radio frequency ablation and the salvage treatment in a
patient with chronic hepatitis B virus infection. Surgeons should be aware of
severe and rare complications before deciding the ablation area and when
performing radio frequency ablation, and should be aware of the relevant salvage
treatment.
PMID- 25135986
TI - Endotoxin-induced lung alveolar cell injury causes brain cell damage.
AB - Sepsis is the most common cause of acute respiratory distress syndrome, a severe
lung inflammatory disorder with an elevated morbidity and mortality. Sepsis and
acute respiratory distress syndrome involve the release of inflammatory mediators
to the systemic circulation, propagating the cellular and molecular response and
affecting distal organs, including the brain. Since it has been reported that
sepsis and acute respiratory distress syndrome contribute to brain dysfunction,
we investigated the brain-lung crosstalk using a combined experimental in vitro
airway epithelial and brain cell injury model. Conditioned medium collected from
an in vitro lipopolysaccharide-induced airway epithelial cell injury model using
human A549 alveolar cells was subsequently added at increasing concentrations (no
conditioned, 2%, 5%, 10%, 15%, 25%, and 50%) to a rat mixed brain cell culture
containing both astrocytes and neurons. Samples from culture media and cells from
mixed brain cultures were collected before treatment, and at 6 and 24 h for
analysis. Conditioned medium at 15% significantly increased apoptosis in brain
cell cultures 24 h after treatment, whereas 25% and 50% significantly increased
both necrosis and apoptosis. Levels of brain damage markers S100 calcium binding
protein B and neuron-specific enolase, interleukin-6, macrophage inflammatory
protein-2, as well as matrix metalloproteinase-9 increased significantly after
treating brain cells with >=2% conditioned medium. Our findings demonstrated that
human epithelial pulmonary cells stimulated with bacterial lipopolysaccharide
release inflammatory mediators that are able to induce a translational clinically
relevant and harmful response in brain cells. These results support a brain-lung
crosstalk during sepsis and sepsis-induced acute respiratory distress syndrome.
PMID- 25135989
TI - Focal therapy will become a standard option for selected men with localized
prostate cancer.
PMID- 25135988
TI - Inclusion of endogenous hormone levels in risk prediction models of
postmenopausal breast cancer.
AB - PURPOSE: Endogenous hormones are risk factors for postmenopausal breast cancer,
and their measurement may improve our ability to identify high-risk women.
Therefore, we evaluated whether inclusion of plasma estradiol, estrone, estrone
sulfate, testosterone, dehydroepiandrosterone sulfate, prolactin, and sex hormone
binding globulin (SHBG) improved risk prediction for postmenopausal invasive
breast cancer (n = 437 patient cases and n = 775 controls not using
postmenopausal hormones) in the Nurses' Health Study. METHODS: We evaluated
improvement in the area under the curve (AUC) for 5-year risk of invasive breast
cancer by adding each hormone to the Gail and Rosner-Colditz risk scores. We used
stepwise regression to identify the subset of hormones most associated with risk
and assessed AUC improvement; we used 10-fold cross validation to assess model
overfitting. RESULTS: Each hormone was associated with breast cancer risk (odds
ratio doubling, 0.82 [SHBG] to 1.37 [estrone sulfate]). Individual hormones
improved the AUC by 1.3 to 5.2 units relative to the Gail score and 0.3 to 2.9
for the Rosner-Colditz score. Estrone sulfate, testosterone, and prolactin were
selected by stepwise regression and increased the AUC by 5.9 units (P = .003) for
the Gail score and 3.4 (P = .04) for the Rosner-Colditz score. In cross
validation, the average AUC change across the validation data sets was 6.0 (P =
.002) and 3.0 units (P = .03), respectively. Similar results were observed for
estrogen receptor-positive disease (selected hormones: estrone sulfate,
testosterone, prolactin, and SHBG; change in AUC, 8.8 [P < .001] for Gail score
and 5.8 [P = .004] for Rosner-Colditz score). CONCLUSION: Our results support
that endogenous hormones improve risk prediction for invasive breast cancer and
could help identify women who may benefit from chemoprevention or more screening.
PMID- 25135990
TI - Calcium/magnesium infusion for oxaliplatin-induced neuropathy: protective or not?
PMID- 25135991
TI - Patterns of relapse in patients with clinical stage I testicular cancer managed
with active surveillance.
AB - PURPOSE: To evaluate the performance of active surveillance as a management
strategy in broad populations and to inform the development of surveillance
schedules by individual patient data regarding timing and type of relapse.
METHODS: Retrospective study including data from 2,483 clinical stage I (CSI)
patients, 1,139 CSI nonseminoma and 1,344 CSI seminoma managed with active
surveillance, with the majority treated between 1998 and 2010. Clinical outcomes
including relapse and death, time distribution, extent of relapse and method of
relapse detection observed on active surveillance were recorded. RESULTS: Relapse
occurred in 221 (19%) CSI-nonseminoma and 173 (13%) CSI-seminoma patients. Median
time to relapse was 4 months (range, 2-61 months), 8 months (range, 2-77 months)
and 14 months (range, 2-84 months) for lymphovascular invasion-positive CSI
nonseminoma, lymphovascular invasion-negative CSI nonseminoma and CSI seminoma.
Most relapses were observed within the first 2 years/3 years after orchiectomy
for CSI nonseminoma (90%)/CSI seminoma (92%). Relapses were detected by computed
tomography scan/tumor-markers in 87%/3% of seminoma recurrences, in 48%/38% of
lymphovascular invasion-negative and 41%/61% of lymphovascular invasion-positive
patients, respectively. 90% of CSI-nonseminoma and 99% of CSI-seminoma relapses
exhibited International Germ Cell Collaborative Group good-risk features. Three
patients with CSI nonseminoma died of disease (0.3%). One patient with CSI
seminoma and two patients with CSI nonseminoma died because of treatment-related
events. Overall, advanced disease was seen in both early- and late-relapse
patients. All late recurrences were cured with standard therapy. Five-year
disease-specific survival was 99.7% (95% CI, 99.24% to 99.93%). CONCLUSION:
Active surveillance for CSI testis cancer leads to excellent outcomes. The vast
majority of relapses occur within 2 years of orchiectomy for CSI nonseminoma and
within 3 years for CSI seminoma. Late and advanced stage relapse are rarely seen.
These data may inform further refinement of rationally designed surveillance
schedules.
PMID- 25135993
TI - Reply to M. Valerio et al.
PMID- 25135992
TI - Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non
germinal center B-cell phenotype in newly diagnosed diffuse large B-Cell
lymphoma: a phase II study.
AB - PURPOSE: Lenalidomide has significant single-agent activity in relapsed diffuse
large B-cell lymphoma (DLBCL). We demonstrated that lenalidomide can be safely
combined with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine,
and prednisone); this new combination is known as R2CHOP. The goal of this phase
II study was to evaluate the efficacy of this combination in newly diagnosed
DLBCL. PATIENTS AND METHODS: Eligible patients were adults with newly diagnosed
untreated stages II to IV CD20(+) DLBCL. Patients received lenalidomide 25 mg
orally per day on days 1 through 10 with standard-dose R-CHOP every 21 days for
six cycles. All patients received pegfilgrastim on day 2 of each cycle and
aspirin prophylaxis throughout. DLBCL molecular subtype was determined by tumor
immunohistochemistry and classified as germinal center B-cell (GCB) versus non
GCB in the R2CHOP patients and 87 control patients with DLBCL from the Lymphoma
Database who were treated with conventional R-CHOP. RESULTS: In all, 64 patients
with DLBCL were enrolled, and 60 were evaluable for response. The overall
response rate was 98% (59 of 60) with 80% (48 of 60) achieving complete response.
Event-free survival and overall survival (OS) rates at 24 months were 59% (95%
CI, 48% to 74%) and 78% (95% CI, 68% to 90%), respectively. In R-CHOP patients,
24-month progression-free survival (PFS) and OS were 28% versus 64% (P < .001)
and 46% versus 78% (P < .001) in non-GCB DLBCL versus GCB DLBCL, respectively. In
contrast, there was no difference in 24-month PFS or OS for R2CHOP patients on
the basis of non-GCB and GCB subtype (60% v 59% [P = .83] and 83% v 75% [P = .61]
at 2 years, respectively). CONCLUSION: R2CHOP shows promising efficacy in DLBCL.
The addition of lenalidomide appears to mitigate a negative impact of non-GCB
phenotype on patient outcome.
PMID- 25135995
TI - Reply to C.d. Atkins and a. Avan et Al.
PMID- 25135994
TI - Radiation field design in the ACOSOG Z0011 (Alliance) Trial.
AB - PURPOSE: ACOSOG Z0011 established that axillary lymph node dissection (ALND) is
unnecessary in patients with breast cancer with one to two positive sentinel
lymph nodes (SLNs) who undergo lumpectomy, radiotherapy (RT), and systemic
therapy. We sought to ascertain RT coverage of the regional nodes in that trial.
METHODS: We evaluated case report forms completed 18 months after enrollment.
From 2012 to 2013, we collected all available detailed RT records for central
review. RESULTS: Among 605 patients with completed case report forms, 89%
received whole-breast RT. Of these, 89 (15%) were recorded as also receiving
treatment to the supraclavicular region. Detailed RT records were obtained for
228 patients, of whom 185 (81.1%) received tangent-only treatment. Among 142 with
sufficient records to evaluate tangent height, high tangents (cranial tangent
border <= 2 cm from humeral head) were used in 50% of patients (33 of 66)
randomly assigned to ALND and 52.6% (40 of 76) randomly assigned to SLND. Of the
228 patients with records reviewed, 43 (18.9%) received directed regional nodal
RT using >= three fields: 22 in the ALND arm and 21 in the SLND arm. Those
receiving directed nodal RT had greater nodal involvement (P < .001) than those
who did not. Overall, there was no significant difference between treatment arms
in the use of protocol-prohibited nodal fields. CONCLUSION: Most patients treated
in Z0011 received tangential RT alone, and some received no RT at all. Some
patients received directed nodal irradiation via a third field. Further research
is necessary to determine the optimal RT approach in patients with low-volume
axillary disease treated with SLND alone.
PMID- 25135996
TI - Estimating the value of intravenous calcium and magnesium in ameliorating
oxaliplatin-induced neuropathy.
PMID- 25135997
TI - Vitamin D deficiency impairs rituximab-mediated cellular cytotoxicity and outcome
of patients with diffuse large B-cell lymphoma treated with but not without
rituximab.
AB - PURPOSE: To investigate the impact and mechanisms of vitamin D deficiency (VDD)
on the outcome of elderly patients with diffuse large B-cell lymphoma (DLBCL).
PATIENTS AND METHODS: Three hundred fifty-nine pretreatment 25-hydroxyvitamin D3
(25[OH]D3) serum levels from the RICOVER-60 study (Six Versus Eight Cycles of
Biweekly CHOP-14 With or Without Rituximab in Elderly Patients With Aggressive
CD20+ B-Cell Lymphomas) and 63 from the RICOVER-noRTh study (an amendment to the
RICOVER-60 study in which patients received six cycles of cyclophosphamide,
doxorubicin, vincristine, and prednisone administered at an interval of 2 weeks
plus two cycles of rituximab [R-CHOP-14], but without radiotherapy) were
determined by chemoluminescent immunoassay. Rituximab-mediated cellular
cytotoxicity (RMCC) was assessed by lactate dehydrogenase release assay of CD20+
Daudi cells. RESULTS: RICOVER-60 patients with VDD (<= 8 ng/mL) and vitamin D
levels more than 8 ng/mL treated with rituximab had 3-year event-free survival
(EFS) of 59% and 79% and 3-year overall survival (OS) of 70% and 82%,
respectively. These differences were significant in a multivariable analysis
adjusting for International Prognostic Index risk factors with a hazard ratio
(HR) of 2.1 (P = .008) for EFS and 1.9 (P = .040) for OS. EFS was not
significantly different in patients with vitamin D levels <= 8 or more than 8
ng/mL (HR, 1.2; P = .388) treated without rituximab. This was confirmed in an
independent validation set of 63 RICOVER-noRTh patients. RMCC increased
significantly (P < .001) in seven of seven individuals with VDD after
substitution and normalization of their vitamin D levels. CONCLUSION: VDD is a
risk factor for elderly patients with DLBCL treated with R-CHOP. That VDD impairs
RMCC and substitution improves RMCC strongly suggests that vitamin D substitution
enhances rituximab efficacy, which must be confirmed in appropriately designed
prospective trials addressing VDD and substitution not only in DLBCL, but also in
malignancies treated with other antibodies, of which the major mechanism of
action is antibody-dependent cellular cytotoxicity (eg, trastuzumab in breast
cancer and cetuximab in colorectal cancer).
PMID- 25135998
TI - Brentuximab vedotin in the front-line treatment of patients with CD30+ peripheral
T-cell lymphomas: results of a phase I study.
AB - PURPOSE: Front-line treatment of peripheral T-cell lymphomas (PTCL) involves
regimens such as cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP)
and results in a 5-year overall survival (OS) rate of less than 50%. This phase I
open-label study evaluated the safety and activity of brentuximab vedotin
administered sequentially with CHOP or in combination with CHP (CHOP without
vincristine) as front-line treatment in patients with CD30(+) PTCL. PATIENTS AND
METHODS: Patients received sequential treatment (once every 3 weeks) with
brentuximab vedotin 1.8 mg/kg (two cycles) followed by CHOP (six cycles) or
brentuximab vedotin 1.8 mg/kg plus CHP (BV+CHP) for six cycles (once every 3
weeks). Responders received single-agent brentuximab vedotin for eight to 10
additional cycles (for a total of 16 cycles). The primary objective was
assessment of safety; secondary end points included objective response rate,
complete remission (CR) rate, progression-free survival rate (PFS), and OS. There
were no prespecified comparisons of the two treatment approaches. RESULTS: After
sequential treatment, 11 (85%) of 13 patients achieved an objective response (CR
rate, 62%; estimated 1-year PFS rate, 77%). Grade 3/4 adverse events occurred in
eight (62%) of 13 patients. At the end of combination treatment, all patients (n
= 26) achieved an objective response (CR rate, 88%; estimated 1-year PFS rate,
71%). All seven patients without anaplastic large-cell lymphoma achieved CR.
Grade 3/4 adverse events (>= 10%) in the combination-treatment group were febrile
neutropenia (31%), neutropenia (23%), anemia (15%), and pulmonary embolism (12%).
CONCLUSION: Brentuximab vedotin, administered sequentially with CHOP or in
combination with CHP, had a manageable safety profile and exhibited substantial
antitumor activity in newly diagnosed patients with CD30(+) PTCL. A randomized
phase III trial is under way, comparing BV+CHP with CHOP (clinical trial No.
NCT01777152).
PMID- 25135999
TI - Strength and function response to clinical interventions of older women
categorized by weakness and low lean mass using classifications from the
Foundation for the National Institute of Health sarcopenia project.
AB - BACKGROUND: The Foundation for the National Institutes of Health Sarcopenia
Project developed data-driven cut-points for clinically meaningful weakness and
low lean body mass. This analysis describes strength and function response to
interventions based on these classifications. METHODS: In data from four
intervention studies, 378 postmenopausal women with baseline and 6-month data
were evaluated for change in grip strength, appendicular lean mass corrected for
body mass index, leg strength and power, and short physical performance battery
(SPPB). Clinical interventions included hormones, exercise, and nutritional
supplementation. Differences in outcomes were evaluated between (i) those with
and without weakness and (ii) those with weakness and low lean mass or with one
but not the other. We stratified analyses by slowness (walking speed <= 0.8 m/s)
and by treatment assignment. RESULTS: The women (72+/-7 years; body mass index of
26+/-5kg/m(2)) were weak (33%), had low lean mass (14%), or both (6%). Those with
weakness increased grip strength, lost less leg power, and gained SPPB score (p <
.05) compared with nonweak participants. Stratified analyses were similar for
grip strength and SPPB. With lean mass in the analysis, individuals with weakness
had larger gains in grip strength and SPPB scores regardless of low lean mass (p
< .01). CONCLUSIONS: Older women with clinically meaningful muscle weakness
increased grip strength and SPPB, regardless of the presence of low lean mass
following treatment with interventions for frailty. Thus, results suggest that
muscle weakness, as defined by the Foundation for the National Institutes of
Health Sarcopenia Project, appears to be a treatable symptom.
PMID- 25136001
TI - Becoming centenarians: disease and functioning trajectories of older US Adults as
they survive to 100.
AB - BACKGROUND: Little is known about the health and functioning of individuals who
become centenarians in the years prior to reaching age 100. We examined long-term
trajectories of disease, disability, and cognitive function in a sample of U.S.
centenarians to determine how their aging experience differs from their
nonsurviving cohort counterparts, and if there is heterogeneity in the aging
experience of centenarians. METHODS: Data are from the 1993-2010 waves of the
nationally representative Health and Retirement Study. Among those who had the
potential to become centenarians, we identified 1,045 respondents who died before
reaching age 100 and 96 who survived to their 100th birthday. Respondents, or
their proxies, reported on diagnosis of six major diseases (hypertension, heart
disease, lung disease, stroke, cancer, and diabetes), limitations in activities
of daily living, and cognitive function. RESULTS: As they age to 100,
centenarians are generally healthier than nonsurviving members of their cohort,
and a number of individuals who become centenarians reach 100 with no self
reported diseases or functional impairments. About 23% of centenarians reached
age 100 with no major chronic disease and approximately the same number had no
disability (18%). Over half (55%) reached 100 without cognitive impairment.
Disease and functioning trajectories of centenarians differ by sex, education,
and marital status. CONCLUSIONS: While some centenarians have poor health and
functioning upon reaching age 100, others are able to achieve exceptional
longevity in relatively good health and without loss of functioning. This study
underscores the importance of examining variation in the growing centenarian
population.
PMID- 25136000
TI - Age-related decline of autocrine pituitary adenylate cyclase-activating
polypeptide impairs angiogenic capacity of rat cerebromicrovascular endothelial
cells.
AB - Aging impairs angiogenic capacity of cerebromicrovascular endothelial cells
(CMVECs) promoting microvascular rarefaction, but the underlying mechanisms
remain elusive. PACAP is an evolutionarily conserved neuropeptide secreted by
endothelial cells and neurons, which confers important antiaging effects. To test
the hypothesis that age-related changes in autocrine PACAP signaling contributes
to dysregulation of endothelial angiogenic capacity, primary CMVECs were isolated
from 3-month-old (young) and 24-month-old (aged) Fischer 344 x Brown Norway rats.
In aged CMVECs, expression of PACAP was decreased, which was associated with
impaired capacity to form capillary-like structures, impaired adhesiveness to
collagen (assessed using electric cell-substrate impedance sensing [ECIS]
technology), and increased apoptosis (caspase3 activity) when compared with young
cells. Overexpression of PACAP in aged CMVECs resulted in increased formation of
capillary-like structures, whereas it did not affect cell adhesion. Treatment
with recombinant PACAP also significantly increased endothelial tube formation
and inhibited apoptosis in aged CMVECs. In young CMVECs shRNA knockdown of
autocrine PACAP expression significantly impaired tube formation capacity,
mimicking the aging phenotype. Cellular and mitochondrial reactive oxygen species
production (dihydroethidium and MitoSox fluorescence, respectively) were
increased in aged CMVECs and were unaffected by PACAP. Collectively, PACAP exerts
proangiogenic effects and age-related dysregulation of autocrine PACAP signaling
may contribute to impaired angiogenic capacity of CMVECs in aging.
PMID- 25136002
TI - Brain pathology contributes to simultaneous change in physical frailty and
cognition in old age.
AB - OBJECTIVE: First, we tested the hypothesis that the rate of change of physical
frailty and cognitive function in older adults are correlated. Next, we examined
if their rates of change are associated with the same brain pathologies. METHODS:
About 2,167 older adults participating in the Religious Orders Study and the Rush
Memory and Aging Project had annual clinical evaluations. Bivariate random
coefficient models were used to estimate simultaneously the rates of change in
both frailty and cognition, and the correlation of change was characterized by a
joint distribution of the random effects. Then, we examined whether postmortem
indices from deceased were associated with the rate of change of frailty and
cognition. RESULTS: During an average follow-up of 6 years, frailty worsened by
0.09 unit/y and cognition declined by 0.08 unit/y. Most individuals showed
worsening frailty and cognition (82.8%); 17% showed progressive frailty alone and
<1% showed only cognitive decline. The rates of change of frailty and cognition
were strongly correlated (rho = -0.73, p < .001). Among deceased (N = 828),
Alzheimer's disease pathology, macroinfarcts, and nigral neuronal loss showed
independent associations with the rate of change in both frailty and cognition
(all ps < .001). In these models, demographics explained about 9% of the
variation in individual rate of change in frailty, and neuropathologies explained
about 8%. In contrast, demographics and neuropathologies accounted for 2% and
30%, respectively, of the variance in the cognitive decline. CONCLUSION: The
rates of change in frailty and cognition are strongly correlated and this may be
due in part because they share a common pathologic basis.
PMID- 25136004
TI - Molecular characterization of Streptococcus agalactiae isolates harboring small
erm(T)-carrying plasmids.
AB - Among 1,827 group B Streptococcus (GBS) strains collected between 2006 and 2013
by the French National Reference Center for Streptococci, 490 (26.8%) strains
were erythromycin resistant. The erm(T) resistance gene was found in six strains
belonging to capsular polysaccharides Ia, III, and V and was carried by the same
mobilizable plasmid, which could be efficiently transferred by mobilization to
GBS and Enterococcus faecalis recipients, thus promoting a broad dissemination of
erm(T).
PMID- 25136005
TI - EUCAST testing of Isavuconazole susceptibility in Aspergillus: comparison of
results for Inoculum standardization using Conidium counting versus optical
density.
AB - The EUCAST E.DEF9.1 standard recommends standardization of the inoculum
concentration by conidium counting using a hemocytometer rather than a
spectrophotometer. In this study, we investigated whether the choice of these
methods influenced isavuconazole MICs. A blinded collection of 30 molecularly
characterized azole-resistant isolates and 10 wild-type Aspergillus fumigatus
isolates was shared with four different laboratories. Additionally, each
laboratory selected approximately 100 A. fumigatus isolates and 50 isolates each
of A. flavus, A. nidulans, A. niger, and A. terreus (1,237 isolates in total).
Three laboratories (laboratories 1 to 3) used conidium counting. One laboratory
standardized the inoculum using a spectrophotometer (that is, by use of the
optical density [OD]) and is referred to as the OD laboratory. Correlation
coefficients, intraclass correlation coefficients, and essential agreement were
calculated, and 2-log-unit differences were assessed (paired t test). The MIC
range for the blinded collection was 0.25 to 16 mg/liter, and a 1-dilution-step
difference between the MIC50 and MIC90 across the four laboratories was detected
and a 2-dilution-step difference between the modal MICs was detected. Compared to
the results for laboratories 1 and 2, a significant correlation was found for the
OD laboratory MIC data (correlation coefficients, 0.85 and 0.93, respectively;
intraclass correlation coefficients, 0.88 and 0.96, respectively). The number of
mutant isolates whose MICs overlapped those of the wild-type isolates was the
lowest for the OD laboratory (14/30 [46.7%] mutant isolates), whereas the numbers
were 18/30 (60%) isolates for laboratory 1, 17/30 (56.7%) isolates for laboratory
2, and 21/30 (70%) isolates for laboratory 3. For the A. flavus, A. fumigatus, A.
nidulans, A. niger, and A. terreus isolates, comparative analysis again defined
the MIC distributions from the OD laboratory to be in excellent agreement with
those from laboratories 1 and 2 across all five Aspergillus spp. The findings
suggest that EUCAST testing using OD determination is an appropriate alternative
for standardization of Aspergillus inoculum concentrations.
PMID- 25136006
TI - Comparison of in vivo and in vitro pharmacodynamics of a humanized regimen of 600
milligrams of Ceftaroline Fosamil every 12 hours against Staphylococcus aureus at
initial inocula of 106 and 108 CFU per milliliter.
AB - In light of the in vivo/in vitro discordance among beta-lactams against Gram
negative pathogens, we compared the in vivo pharmacodynamics of humanized
ceftaroline against 9 Staphylococcus aureus strains (MICs of 0.13 to 1 mg/liter)
from published in vitro studies using standard and high inocula in the murine
thigh infection model. Consistent with the in vitro findings, mean reductions of
>=1 log10 CFU were observed for ceftaroline against all strains using both
standard and high inocula. These results suggest in vivo/in vitro concordance
with no observed inoculum effect.
PMID- 25136003
TI - Effects of tenofovir on cytokines and nucleotidases in HIV-1 target cells and the
mucosal tissue environment in the female reproductive tract.
AB - Tenofovir (TFV) is a reverse transcriptase inhibitor used in microbicide
preexposure prophylaxis trials to prevent HIV infection. Recognizing that changes
in cytokine/chemokine secretion and nucleotidase biological activity can
influence female reproductive tract (FRT) immune protection against HIV
infection, we tested the hypothesis that TFV regulates immune protection in the
FRT. Epithelial cells, fibroblasts, CD4(+) T cells, and CD14(+) cells were
isolated from the endometrium (Em), endocervix (Cx), and ectocervix (Ecx)
following hysterectomy. The levels of proinflammatory cytokines (macrophage
inflammatory protein 3alpha [MIP-3alpha], interleukin 8 [IL-8], and tumor
necrosis factor alpha [TNF-alpha]), the expression levels of specific
nucleotidases, and nucleotidase biological activities were analyzed in the
presence or absence of TFV. TFV influenced mRNA and/or protein cytokines and
nucleotidases in a cell- and site-specific manner. TFV significantly enhanced IL
8 and TNF-alpha secretion by epithelial cells from the Em and Ecx but not from
the Cx. In contrast, in response to TFV, IL-8 secretion was significantly
decreased in Em and Cx fibroblasts but increased with fibroblasts from the Ecx.
When incubated with CD4(+) T cells from the FRT, TFV increased IL-8 (Em and Ecx)
and TNF-alpha (Cx and Ecx) secretion levels. Moreover, when incubated with Em
CD14(+) cells, TFV significantly increased MIP-3alpha, IL-8, and TNF-alpha
secretion levels relative to those of the controls. In contrast, nucleotidase
biological activities were significantly decreased by TFV in epithelial (Cx) and
CD4(+) T cells (Em) but increased in fibroblasts (Em). Our findings indicate that
TFV modulates proinflammatory cytokines, nucleotidase gene expression, and
nucleotidase biological activity in epithelial cells, fibroblasts, CD4(+) T
cells, and CD14(+) cells at distinct sites within the FRT.
PMID- 25136007
TI - Triclosan can select for an AdeIJK-overexpressing mutant of Acinetobacter
baumannii ATCC 17978 that displays reduced susceptibility to multiple
antibiotics.
AB - In order to determine if triclosan can select for mutants of Acinetobacter
baumannii ATCC 17978 that display reduced susceptibilities to antibiotics, we
isolated a triclosan-resistant mutant, A. baumannii AB042, by serial passaging of
A. baumannii ATCC 17978 in growth medium supplemented with triclosan. The
antimicrobial susceptibility of AB042 was analyzed by the 2-fold serial dilution
method. Expression of five different resistance-nodulation-division (RND) pump
encoding genes (adeB, adeG, adeJ, A1S_2818, and A1S_3217), two outer membrane
porin-encoding genes (carO and oprD), and the MATE family pump-encoding gene abeM
was analyzed using quantitative reverse transcriptase (qRT) PCR. A. baumannii
AB042 exhibited elevated resistance to multiple antibiotics, including
piperacillin-tazobactam, doxycycline, moxifloxacin, ceftriaxone, cefepime,
meropenem, doripenem, ertapenem, ciprofloxacin, aztreonam, tigecycline, and
trimethoprim-sulfamethoxazole, in addition to triclosan. Genome sequencing of A.
baumannii AB042 revealed a (116)G->V mutation in fabI, the gene encoding the
target enzyme for triclosan. Expression analysis of efflux pumps showed
overexpression of the AdeIJK pump, and sequencing of adeN, the gene that encodes
the repressor of the adeIJK operon, revealed a 73-bp deletion which would cause a
premature termination of translation, resulting in an inactive truncated AdeN
protein. This work shows that triclosan can select for mutants of A. baumannii
that display reduced susceptibilities to multiple antibiotics from chemically
distinct classes in addition to triclosan resistance. This multidrug resistance
can be explained by the overexpression of the AdeIJK efflux pump.
PMID- 25136008
TI - Identification and characterization of linezolid-resistant cfr-positive
Staphylococcus aureus USA300 isolates from a New York City medical center.
AB - The cfr gene was identified in three linezolid-resistant USA300 methicillin
resistant Staphylococcus aureus (MRSA) isolates collected over a 3-day period at
a New York City medical center in 2011 as part of a routine surveillance program.
Each isolate possessed a plasmid containing a pSCFS3-like cfr gene environment.
Transformation of the cfr-bearing plasmids into the S. aureus ATCC 29213
background recapitulated the expected Cfr antibiogram, including resistance to
linezolid, tiamulin, clindamycin, and florfenicol and susceptibility to
tedizolid.
PMID- 25136009
TI - In vivo efficacy of apramycin in murine infection models.
AB - Apramycin is a unique aminoglycoside with a dissociation of antibacterial
activity and ototoxicity. We assessed the antibacterial efficacy of apramycin in
two murine models of infection, Mycobacterium tuberculosis aerosol infection and
Staphylococcus aureus septicemia. In both infection models, the efficacy of
apramycin was comparable to that of amikacin. These results suggest that
apramycin has the potential to become a clinically useful agent against drug
resistant pathogens and support further development of this promising unique
aminoglycoside.
PMID- 25136010
TI - Role of PBPD1 in stimulation of Listeria monocytogenes biofilm formation by
subminimal inhibitory beta-lactam concentrations.
AB - Disinfectant-tolerant Listeria monocytogenes biofilms can colonize surfaces that
come into contact with food, leading to contamination and, potentially, food
borne illnesses. To better understand the process of L. monocytogenes biofilm
formation and dispersal, we screened 1,120 off-patent FDA-approved drugs and
identified several that modulate Listeria biofilm development. Among the hits
were more than 30 beta-lactam antibiotics, with effects ranging from inhibiting
(<=50%) to stimulating (>=200%) biofilm formation compared to control. Most beta
lactams also dispersed a substantial proportion of established biofilms. This
phenotype did not necessarily involve killing, as >50% dispersal could be
achieved with concentrations as low as 1/20 of the MIC of some cephalosporins.
Penicillin-binding protein (PBP) profiling using a fluorescent penicillin
analogue showed similar inhibition patterns for most beta-lactams, except that
biofilm-stimulatory drugs did not bind PBPD1, a low-molecular-weight d,d
carboxypeptidase. Compared to the wild type, a pbpD1 mutant had an attenuated
biofilm response to stimulatory beta-lactams. The cephalosporin-responsive CesRK
two-component regulatory system, whose regulon includes PBPs, was not required
for the response. The requirement for PBPD1 activity for beta-lactam stimulation
of L. monocytogenes biofilms shows that the specific set of PBPs that are
inactivated by a particular drug dictates whether a protective biofilm response
is provoked.
PMID- 25136012
TI - Validation of a model to predict the risk of nephrotoxicity in patients receiving
colistin.
AB - Despite concerns about its nephrotoxicity, colistin often remains the only
effective agent for treating multidrug-resistant Gram-negative infections.
Published studies have reported a wide range of nephrotoxicity risk factors. To
assess the clinical utility of various models, we compared their performances for
predicting the risk of nephrotoxicity. We identified a model demonstrating
reasonable overall risk assessment, with an observed/expected ratio of 1.29 (95%
confidence interval [CI], 0.68 to 1.90) and a positive predictive value of 87.5%
for identifying patients at high risk of developing nephrotoxicity.
PMID- 25136011
TI - Antimicrobial resistance in Salmonella enterica Serovar Typhi isolates from
Bangladesh, Indonesia, Taiwan, and Vietnam.
AB - We characterized Salmonella enterica serovar Typhi isolates from Bangladesh,
Indonesia, Taiwan, and Vietnam to investigate their genetic relatedness and
antimicrobial resistance. The isolates from Bangladesh and Vietnam were
genetically closely related but were distant from those from Indonesia and
Taiwan. All but a few isolates from Indonesia and Taiwan were susceptible to all
antimicrobials tested. The majority of isolates from Bangladesh and Vietnam were
multidrug resistant (MDR) and belonged to the widespread haplotype H58 clone.
IncHI1 plasmids were detected in all MDR S. Typhi isolates from Vietnam but in
only 15% of MDR isolates from Bangladesh. Resistance genes in the majority of MDR
S. Typhi isolates from Bangladesh should reside in the chromosome. Among the
isolates from Bangladesh, 82% and 40% were resistant to various concentrations of
nalidixic acid and ciprofloxacin, respectively. Several resistance mechanisms,
including alterations in gyrase A, the presence of QnrS, and enhanced efflux
pumps, were involved in the reduced susceptibility and resistance to
fluoroquinolones. Intensive surveillance is necessary to monitor the spread of
chromosome-mediated MDR and fluoroquinolone-resistant S. Typhi emerging in
Bangladesh.
PMID- 25136014
TI - Ceftaroline-Fosamil efficacy against methicillin-resistant Staphylococcus aureus
in a rabbit prosthetic joint infection model.
AB - Ceftaroline (CPT), the active metabolite of the prodrug ceftaroline-fosamil (CPT
F), demonstrates in vitro bactericidal activity against methicillin-resistant
Staphylococcus aureus (MRSA) and is effective in rabbit models of difficult-to
treat MRSA endocarditis and acute osteomyelitis. However, its in vivo efficacy in
a prosthetic joint infection (PJI) model is unknown. Using a MRSA-infected knee
PJI model in rabbits, the efficacies of CPT-F or vancomycin (VAN) alone and
combined with rifampin (RIF) were compared. After each partial knee replacement
with a silicone implant that fit into the tibial intramedullary canal was
performed, 5 * 10(7) MRSA CFU (MICs of 0.38, 0.006, and 1 mg/liter for CPT, RIF,
and VAN, respectively) was injected into the knee. Infected animals were randomly
assigned to receive no treatment (controls) or CPT-F (60 mg/kg of body weight
intramuscularly [i.m.]), VAN (60 mg/kg i.m.), CPT-F plus RIF (10 mg/kg i.m.), or
VAN plus RIF starting 7 days postinoculation and lasting for 7 days. Surviving
bacteria in crushed tibias were counted 3 days after ending treatment. Although
the in vivo mean log10 CFU/g of CPT-treated (3.0 +/- 0.9, n = 12) and VAN-treated
(3.5 +/- 1.1, n = 12) crushed bones was significantly lower than those of
controls (5.6 +/- 1.1, n = 14) (P < 0.001), neither treatment fully sterilized
the bones (3/12 were sterile with each treatment). The mean log10 CFU/g values
for the antibiotics in combination with RIF were 1.9 +/- 0.5 (12/14 were sterile)
for CPT-F and 1.9 +/- 0.5 (12/14 were sterile) for VAN. In this MRSA PJI model,
the efficacies of CPT-F and VAN did not differ; thus, CPT appears to be a
promising antimicrobial agent for the treatment of MRSA PJIs.
PMID- 25136013
TI - Molecular features of community-associated extended-spectrum-beta-lactamase
producing Escherichia coli strains in the United States.
AB - We characterized 30 community-associated extended-spectrum-beta-lactamase
producing Escherichia coli isolates collected from five hospitals in the United
States. Nineteen sequence types were identified. All sequence type 131 (ST131)
isolates had the fimH30 allele. IncFII-FIA-FIB was the most common replicon type
among the blaCTX-M-carrying plasmids, followed by IncFII-FIA and IncA/C.
Restriction analysis of the IncFII-FIA-FIB and IncFII-FIA plasmids yielded
related profiles for plasmids originating from different hospitals. The plasmids
containing blaCTX-M or blaSHV were stably maintained after serial passages.
PMID- 25136015
TI - Safety, tolerability, and efficacy of GSK1322322 in the treatment of acute
bacterial skin and skin structure infections.
AB - GSK1322322 represents a new class of antibiotics that targets an essential
bacterial enzyme required for protein maturation, peptide deformylase. This
multicenter, randomized, phase IIa study compared the safety, tolerability, and
efficacy of GSK1322322 at 1,500 mg twice daily (b.i.d.) with that of linezolid at
600 mg b.i.d. in patients suspected of having Gram-positive acute bacterial skin
and skin structure infections (ABSSSIs). The primary endpoint was assessment of
the safety of GSK1322322, and a key secondary endpoint was the number of subjects
with a >=20% decrease in lesion area from the baseline at 48 and 72 h after
treatment initiation. GSK1322322 administration was associated with mild-to
moderate drug-related adverse events, most commonly, nausea, vomiting, diarrhea,
and headache. Adverse events (86% versus 74%) and withdrawals (28% versus 11%)
were more frequent in the GSK1322322-treated group. Treatment with GSK1322322 and
linezolid was associated with >=20% decreases from the baseline in the lesion
area in 73% (36/49) and 92% (24/26) of the patients, respectively, at the 48-h
assessment and in 96% (44/46) and 100% (25/25) of the patients, respectively, at
the 72-h assessment. Reductions in exudate/pus, pain, and skin infection scores
were comparable between the GSK1322322 and linezolid treatments. The clinical
success rates within the intent-to-treat population and the per-protocol
population that completed this study were 67 and 91%, respectively, in the
GSK1322322-treated group and 89 and 100%, respectively, in the linezolid-treated
group. These results will be used to guide dose selection in future studies with
GSK1322322 to optimize its tolerability and efficacy in patients with ABSSSIs.
(This study has been registered at ClinicalTrials.gov under registration no.
NCT01209078 and at http://www.gsk-clinicalstudyregister.com [PDF113414].).
PMID- 25136016
TI - Efficacy of a Ceftazidime-Avibactam combination in a murine model of Septicemia
caused by Enterobacteriaceae species producing ampc or extended-spectrum beta
lactamases.
AB - Avibactam is a novel non-beta-lactam beta-lactamase inhibitor that has been shown
in vitro to inhibit class A, class C, and some class D beta-lactamases. It is
currently in phase 3 of clinical development in combination with ceftazidime. In
this study, the efficacy of ceftazidime-avibactam was evaluated in a murine
septicemia model against five ceftazidime-susceptible (MICs of 0.06 to 0.25
MUg/ml) and 15 ceftazidime-resistant (MICs of 64 to >128 MUg/ml) species of
Enterobacteriaceae, bearing either TEM, SHV, CTX-M extended-spectrum, or AmpC
beta-lactamases. In the first part of the study, ceftazidime-avibactam was
administered at ratios of 4:1 and 8:1 (wt/wt) to evaluate the optimal ratio for
efficacy. Against ceftazidime-susceptible isolates of Klebsiella pneumoniae and
Escherichia coli, ceftazidime and ceftazidime-avibactam demonstrated similar
efficacies (50% effective doses [ED50] of <1.5 to 9 mg/kg of body weight),
whereas against ceftazidime-resistant beta-lactamase-producing strains
(ceftazidime ED50 of >90 mg/kg), the addition of avibactam restored efficacy to
ceftazidime (ED50 dropped to <5 to 65 mg/kg). In a subsequent study, eight
isolates (two AmpC and six CTX-M producers) were studied in the septicemia model.
Ceftazidime-avibactam was administered at a 4:1 (wt/wt) ratio, and the efficacy
was compared to that of the 4:1 (wt/wt) ratio of either piperacillin-tazobactam
or cefotaxime-avibactam. Against the eight isolates, ceftazidime-avibactam was
the more effective combination, with ED50 values ranging from 2 to 27 mg/kg
compared to >90 mg/kg and 14 to >90 mg/kg for piperacillin-tazobactam and
cefotaxime-avibactam, respectively. This study demonstrates that the potent in
vitro activity observed with the ceftazidime-avibactam combination against
ceftazidime-resistant Enterobacteriaceae species bearing class A and class C beta
lactamases translated into good efficacy in the mouse septicemia model.
PMID- 25136017
TI - A first-in-human randomized, double-blind, placebo-controlled, single- and
multiple-ascending oral dose study of novel Imidazolopiperazine KAF156 to assess
its safety, tolerability, and pharmacokinetics in healthy adult volunteers.
AB - KAF156 belongs to a new class of antimalarial, the imidazolopiperazines, and is
currently in clinical development for the treatment of uncomplicated malaria.
This first-in-human, single- and multiple-ascending-dose study in 70 healthy male
volunteers determined the maximum oral dose of KAF156 tolerated by healthy adults
and derived pharmacokinetic data (including preliminary food effect) to enable
dose calculations for malaria patients. KAF156 was studied in single-dose cohorts
(10 to 1,200 mg, including one 400-mg food effect cohort (4 to 10
subjects/cohort), and in multiple-dose cohorts (60 to 600 mg once daily for 3
days; 8 subjects/cohort). The follow-up period was 6 to 14 days after the last
dose. KAF156 was tolerated, with self-limited mild to moderate gastrointestinal
and neurological adverse events. In treated subjects after single doses, headache
(n = 4; 11.1%), diarrhea (n = 3; 8.3%), dizziness (n = 3; 8.3%), and abdominal
pain (n = 2; 5.6%) were the most common adverse events. Headache (n = 4; 16.7%),
nausea (n = 3; 12.5%), upper respiratory tract infection (n = 3; 12.5%), and
dizziness (n = 2; 8.3%) were the most common adverse events following multiple
doses. KAF156 time to maximum concentration (Tmax) was between 1.0 and 6.0 h.
Both the area under the concentration-time curve (AUC) and maximum concentration
(Cmax) increased more than dose-proportionally in both single- and multiple
ascending-dose cohorts (terminal half-life, 42.5 to 70.7 h). There was no
significant accumulation over 3-day repeated administration. The extent of
absorption was not significantly affected by food at a single dose of 400 mg,
while mean Cmax decreased from 778 ng/ml to 627 ng/ml and Tmax was delayed from a
median of 3.0 h under fasting conditions to 6.0 h under fed conditions. Renal
elimination is a minor route.
PMID- 25136018
TI - Changes in pneumococcal serotypes and antimicrobial resistance after introduction
of the 13-valent conjugate vaccine in the United States.
AB - Ongoing surveillance for Streptococcus pneumoniae is needed to assess the impact
of the pneumococcal conjugate vaccine introduced in 2010 (PCV13). Forty-two U.S.
centers submitted S. pneumoniae isolates between 1 October 2012 and 31 March
2013. Susceptibility testing was performed by use of a broth dilution method as
recommended by the Clinical and Laboratory Standards Institute. Serotyping was
performed by multiplex PCR and the Quellung reaction. Multidrug resistance (MDR)
was defined as nonsusceptibility to penicillin (PNSP; MIC >= 0.12 MUg/ml)
combined with resistance to >=2 non-beta-lactam antimicrobials. Penicillin
resistant S. pneumoniae (PRSP) was defined as a penicillin MIC of >=2 MUg/ml. For
the 1,498 isolates collected during 2012-13, the PRSP and MDR rates were 14.2 and
21.0%, respectively. These percentages were lower than rates obtained in a
surveillance study conducted 4 years earlier in 2008-09 (17.0 and 26.6%,
respectively). The most common serotypes identified in 2012-13 were 3, 35B, and
19A, each representing 9 to 10% of all isolates. The largest percentage of PNSP
in 2012-13 were found in serotypes 35B (24.8%), 19A (23.5%), and 15A (10.3%).
Predominant PRSP serotypes were 19A (54.5%), 35B (28.2%), and 19F (7.0%). Major
MDR serotypes were 19A (38.5%), 15A (16.9%), 6C (8.3%), and 35B (6.4%). The
change in prevalence of PCV13 serotypes (43.4 to 27.1%) was primarily due to a
decrease in serotype 19A strains, i.e., 22% of all strains in 2008-09 to 10% of
all strains in 2012-13. Among the PNSP subset, serotypes showing a proportional
increase were 35B, 15B, and 23B. Among MDR strains, the largest proportional
increases were observed in serotypes 35B, 15B, and 23A.
PMID- 25136019
TI - Use of microdosing and accelerator mass spectrometry to evaluate the
pharmacokinetic linearity of a novel tricyclic GyrB/ParE inhibitor in rats.
AB - Determining the pharmacokinetics (PKs) of drug candidates is essential for
understanding their biological fate. The ability to obtain human PK information
early in the drug development process can help determine if future development is
warranted. Microdosing was developed to assess human PKs, at ultra-low doses,
early in the drug development process. Microdosing has also been used in animals
to confirm PK linearity across subpharmacological and pharmacological dose
ranges. The current study assessed the PKs of a novel antimicrobial preclinical
drug candidate (GP-4) in rats as a step toward human microdosing studies. Dose
proportionality was determined at 3 proposed therapeutic doses (3, 10, and 30
mg/kg of body weight), and PK linearity between a microdose and a pharmacological
dose was assessed in Sprague-Dawley rats. Plasma PKs over the 3 pharmacological
doses were proportional. Over the 10-fold dose range, the maximum concentration
in plasma and area under the curve (AUC) increased 9.5- and 15.8-fold,
respectively. PKs from rats dosed with a (14)C-labeled microdose versus a (14)C
labeled pharmacological dose displayed dose linearity. In the animals receiving a
microdose and the therapeutically dosed animals, the AUCs from time zero to
infinity were 2.6 ng . h/ml and 1,336 ng . h/ml, respectively, and the terminal
half-lives were 5.6 h and 1.4 h, respectively. When the AUC values were
normalized to a dose of 1.0 mg/kg, the AUC values were 277.5 ng . h/ml for the
microdose and 418.2 ng . h/ml for the pharmacological dose. This 1.5-fold
difference in AUC following a 300-fold difference in dose is considered linear
across the dose range. On the basis of the results, the PKs from the microdosed
animals were considered to be predictive of the PKs from the therapeutically
dosed animals.
PMID- 25136020
TI - Characterization of a novel AmpC beta-lactamase produced by a carbapenem
resistant Cedecea davisae clinical isolate.
AB - A Cedecea davisae isolate, which was intermediate or resistant to third
generation cephalosporins and carbapenems, was recovered from a urine sample.
Susceptibility testing, isoelectric focusing, and analysis of outer membrane
proteins showed that AmpC beta-lactamase expression combined with porin
deficiency accounted for the carbapenem resistance. A cloning experiment followed
by phenotypic and enzymatic characterization identified a novel class C enzyme
that was phylogenetically and biochemically close to the chromosome-borne beta
lactamases of the genera Enterobacter and Citrobacter.
PMID- 25136021
TI - In vitro combination of isavuconazole with micafungin or amphotericin B
deoxycholate against medically important molds.
AB - Whether isavuconazole, an extended-spectrum triazole, possesses synergistic
activity in combination therapy with echinocandins or amphotericin B for the
treatment of invasive molds infections has not been studied. Our in vitro
combination studies showed that isavuconazole and micafungin are synergistically
active against Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus,
and Cunninghamella bertholletiae. These results suggest that isavuconazole, in
combination with micafungin, may have a role in the treatment of invasive
aspergillosis and warrants further investigation.
PMID- 25136022
TI - Novel insights into the mechanism of inhibition of MmpL3, a target of multiple
pharmacophores in Mycobacterium tuberculosis.
AB - MmpL3, a resistance-nodulation-division (RND) superfamily transporter, has been
implicated in the formation of the outer membrane of Mycobacterium tuberculosis;
specifically, MmpL3 is required for the export of mycolic acids in the form of
trehalose monomycolates (TMM) to the periplasmic space or outer membrane of M.
tuberculosis. Recently, seven series of inhibitors identified by whole-cell
screening against M. tuberculosis, including the antituberculosis drug candidate
SQ109, were shown to abolish MmpL3-mediated TMM export. However, this mode of
action was brought into question by the broad-spectrum activities of some of
these inhibitors against a variety of bacterial and fungal pathogens that do not
synthesize mycolic acids. This observation, coupled with the ability of three of
these classes of inhibitors to kill nonreplicating M. tuberculosis bacilli, led
us to investigate alternative mechanisms of action. Our results indicate that the
inhibitory effects of adamantyl ureas, indolecarboxamides,
tetrahydropyrazolopyrimidines, and the 1,5-diarylpyrrole BM212 on the transport
activity of MmpL3 in actively replicating M. tuberculosis bacilli are, like that
of SQ109, most likely due to their ability to dissipate the transmembrane
electrochemical proton gradient. In addition to providing novel insights into the
modes of action of compounds reported to inhibit MmpL3, our results provide the
first explanation for the large number of pharmacophores that apparently target
this essential inner membrane transporter.
PMID- 25136023
TI - Genetic and kinetic characterization of the novel AmpC beta-lactamases DHA-6 and
DHA-7.
AB - During a Spanish surveillance study, two natural variants of DHA beta-lactamases,
DHA-6 and DHA-7, were found, with the replacements Ala226Thr and Phe322Ser,
respectively, with respect to DHA-1. The DHA-6 and DHA-7 enzymes were isolated
from Escherichia coli and Enterobacter cloacae clinical isolates, respectively.
The aim of this study was to genetically, microbiologically, and biochemically
characterize the DHA-6 and DHA-7 beta-lactamases. The blaDHA-6 and blaDHA-7 genes
were located in the I1 and HI2 incompatibility group plasmids of 87.3 and 310.4
kb, respectively. The genetic contexts of blaDHA-6 and blaDHA-7 were similar to
that already described for the blaDHA-1 gene and included the qnrB4 and aadA
genes. The MICs for cephalothin, aztreonam, cefotaxime, and ceftazidime were 8-
to 32-fold lower for DHA-6 than for DHA-1 or DHA-7 expressed in the same isogenic
E. coli TG1 strain. Interestingly, the MIC for cefoxitin was higher in the DHA-6
expressing transformant than in DHA-1 or DHA-7. Biochemical studies with pure
beta-lactamases revealed slightly lower catalytic efficiencies of DHA-6 against
cephalothin, ceftazidime, and cefotaxime than those of DHA-1 and DHA-7. To
understand this behavior, stability experiments were carried out and showed that
the DHA-6 protein displayed significantly higher stability than the DHA-1 and DHA
7 enzymes. The proximity of Thr226 to the N terminus in the tertiary protein
structure in DHA-6 may promote this stabilization and, consequently, may induce a
slight reduction in the dynamic of this enzyme that primarily affects the
hydrolysis of some of the bulkiest antibiotics.
PMID- 25136024
TI - Pharmacokinetics of tedizolid in subjects with renal or hepatic impairment.
AB - Two open-label, single-dose, parallel-group studies were conducted to
characterize the pharmacokinetics of the novel antibacterial tedizolid and the
safety of tedizolid phosphate, its prodrug, in renally or hepatically impaired
subjects. Tedizolid pharmacokinetics in subjects with severe renal impairment
without dialysis support was compared with that of matched control subjects with
normal renal function. Effects of hemodialysis on tedizolid pharmacokinetics were
determined in a separate cohort of subjects undergoing long-term hemodialysis.
Effects of hepatic impairment on tedizolid pharmacokinetics were determined in
subjects with moderate or severe hepatic impairment and compared with those of
matched control subjects with normal hepatic function. Each participant received
a single oral (hepatic impairment) or intravenous (renal impairment) dose of
tedizolid phosphate at 200 mg; hemodialysis subjects received two doses
(separated by 7 days), before and after dialysis, in a crossover fashion. The
pharmacokinetics of tedizolid was similar in subjects with severe renal
impairment and controls (~8% lower area under the concentration-time curve [AUC],
with a nearly identical peak concentration) and in subjects undergoing
hemodialysis before and after tedizolid phosphate administration (~9% lower AUC,
with a 15% higher peak concentration); <10% of the dose was removed during 4 h of
hemodialysis. Tedizolid pharmacokinetics was only minimally altered in subjects
with moderate or severe hepatic impairment; the AUC was increased approximately
22% and 34%, respectively, compared with that of subjects in the control group.
Tedizolid phosphate was generally well tolerated in all participants. These
results suggest that tedizolid phosphate dose adjustments are not necessary in
patients with any degree of renal or hepatic impairment. (This study has been
registered at ClinicalTrials.gov under registration numbers NCT01452828 [renal
study] and NCT01431833 [hepatic study].).
PMID- 25136025
TI - Characterization of a P1-like bacteriophage carrying an SHV-2 extended-spectrum
beta-lactamase from an Escherichia coli strain.
AB - P1 bacteriophages lysogenize bacteria as independent plasmid-like elements. We
describe here a P1-like bacteriophage, RCS47, carrying a blaSHV-2 gene, isolated
from a clinical strain of Escherichia coli from phylogroup B1, and we report the
prevalence of P1-like prophages in natural E. coli isolates. We found that 70% of
the sequence of RCS47, a 115-kb circular molecule, was common to the reference P1
bacteriophage under GenBank accession no. AF234172.1, with the shared sequences
being 99% identical. RCS47 had acquired two main foreign DNA fragments: a 9,636
bp fragment mobilized by two IS26 elements containing a blaSHV-2 gene, and an
8,544-bp fragment mobilized by two IS5 elements containing an operon encoding a
dimethyl sulfoxide reductase. The reference P1 prophage plasmid replication gene
belonged to the IncY incompatibility group, whereas that of RCS47 was from an
unknown group. The lytic capacity of RCS47 and blaSHV-2 gene transduction,
through the lysogenization of RCS47 in the recipient E. coli strains, were not
demonstrated. The prevalence of P1-like prophages in various animal and human E.
coli strain collections, as determined by the PCR detection of repL, the lytic
replication gene, was 12.6%. No differences in the prevalences of these prophages
were found between extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL
producing strains (P = 0.69), but this prevalence was lower in phylogroup B2 than
in the other phylogroups (P = 0.008), suggesting epistatic interactions between
P1 family phages and the genetic background of E. coli strains. P1-like phages
are part of the mobile elements that carry antibiotic resistance. The high
prevalence of P1-like prophages suggests their role may be underestimated.
PMID- 25136026
TI - Synthesis of metallo-beta-lactamase VIM-2 is associated with a fitness reduction
in Salmonella enterica Serovar Typhimurium.
AB - Antibiotic resistance, especially due to beta-lactamases, has become one of the
main obstacles in the correct treatment of Salmonella infections; furthermore,
antibiotic resistance determines a gain of function that may encompass a
biological cost, or fitness reduction, to the resistant bacteria. The aim of this
work was to determine in vitro if the production of the class B beta-lactamase
VIM-2 determined a fitness cost for Salmonella enterica serovar Typhimurium. To
that end the gene blaVIM-2 was cloned into the virulent strain S. Typhimurium
SL1344, using both the tightly regulated pBAD22 vector and the natural plasmid
pST12, for inducible and constitutive expression, respectively. Fitness studies
were performed by means of motility, growth rate, invasiveness in epithelial
cells, and plasmid stability. The expression of blaVIM-2 was accompanied by
alterations in micro- and macroscopic morphology and reduced growth rate and
motility, as well as diminished invasiveness in epithelial cells. These results
suggest that VIM-2 production entails a substantial fitness cost for S.
Typhimurium, which in turn may account for the extremely low number of reports of
metallo-beta-lactamase-producing Salmonella spp.
PMID- 25136027
TI - Association between vancomycin trough concentration and area under the
concentration-time curve in neonates.
AB - National treatment guidelines for invasive methicillin-resistant Staphylococcus
aureus (MRSA) infections recommend targeting a vancomycin 24-h area under the
concentration-time curve (AUC0-24)-to-MIC ratio of >400. The range of vancomycin
trough concentrations that best predicts an AUC0-24 of >400 in neonates is not
known. This understanding would help clarify target trough concentrations in
neonates when treating MRSA. A retrospective chart review from a level III
neonatal intensive care unit was performed to identify neonates treated with
vancomycin over a 5-year period. Vancomycin concentrations and clinical
covariates were utilized to develop a one-compartment population pharmacokinetic
model and examine the relationships between trough and AUC0-24 in the study
neonates. Monte Carlo simulations were performed to examine the effect of dose,
postmenstrual age (PMA), and serum creatinine level on trough and AUC0-24
achievement. A total of 1,702 vancomycin concentrations from 249 neonates were
available for analysis. The median (interquartile range) PMA was 39 weeks (32 to
42 weeks) and weight was 2.9 kg (1.6 to 3.7 kg). Vancomycin clearance was
predicted by weight, PMA, and serum creatinine level. At a trough of 10 mg/liter,
89% of the study neonates had an AUC0-24 of >400. Monte Carlo simulations
demonstrated that troughs ranging from 7 to 11 mg/liter were highly predictive of
an AUC0-24 of >400 across a range of PMA, serum creatinine levels, and vancomycin
doses. However, a trough of >=10 mg/liter was not readily achieved in most
simulated subgroups using routine starting doses. Higher starting doses
frequently resulted in troughs of >20 mg/liter. A vancomycin trough of ~10
mg/liter is likely adequate for most neonates with invasive MRSA infections based
on considerations of the AUC0-24. Due to pharmacokinetic and clinical
heterogeneity in neonates, consistently achieving this target vancomycin exposure
with routine starting doses is difficult. More robust clinical dosing support
tools are needed to help clinicians with dose individualization.
PMID- 25136028
TI - Tedizolid population pharmacokinetics, exposure response, and target attainment.
AB - Tedizolid phosphate is a novel antibacterial prodrug that is rapidly and
extensively converted to its active moiety, tedizolid. We developed a population
pharmacokinetics (PK) model for tedizolid using pooled data from seven densely
and sparsely sampled clinical trials evaluating oral and intravenous tedizolid.
Model-derived exposure estimates were evaluated for relationships to select
efficacy and safety outcomes. A two-compartment model with sigmoidal absorption,
absolute bioavailability, and linear elimination described the PK data well.
Variability was small (clearance, 31% coefficient of variation; volume, 13.4%
coefficient of variation), and absolute bioavailability was high (86%). No
clinically significant covariate effects on tedizolid PK were found. Based on
phase 3 data evaluating 200-mg once-daily tedizolid for acute bacterial skin and
skin structure infections (ABSSSI), no relationships were seen between various
efficacy outcomes and estimated tedizolid exposure; the estimated exposure range
(free-drug area under the concentration-time curve over 24 h at steady state
[AUCss(0-24)], 7 to 50 MUg . h/ml) in these patients was modest. Safety data
modeling, using once-daily doses of up to 400 mg, showed a small increase in the
probability of an adverse event with increasing model-estimated tedizolid
exposure; no such relationship was observed when specifically evaluating the 200
mg dose. There were no trends in neutrophil or platelet counts with increasing
tedizolid exposure. Target attainment simulations for 200-mg tedizolid indicated
a 98.31% probability of attaining the target measure (AUC for the free, unbound
fraction of a drug [fAUC]/MIC = 3) against a Staphylococcus aureus strain for
which the MIC was <=0.5 MUg/ml. These findings support 200-mg tedizolid once
daily as the optimum dose for treatment of ABSSSI.
PMID- 25136029
TI - Distinct roles of major peptidoglycan recycling enzymes in beta-Lactamase
production in Shewanella oneidensis.
AB - beta-Lactam antibiotics were the earliest discovered and are the most widely used
group of antibiotics that work by inactivating penicillin-binding proteins to
inhibit peptidoglycan biosynthesis. As one of the most efficient defense
strategies, many bacteria produce beta-lactam-degrading enzymes, beta-lactamases,
whose biochemical functions and regulation have been extensively studied. A
signal transduction pathway for beta-lactamase induction by beta-lactam
antibiotics, consisting of the major peptidoglycan recycling enzymes and the LysR
type transcriptional regulator, AmpR, has been recently unveiled in some
bacteria. Because inactivation of some of these proteins, especially the permease
AmpG and the beta-hexosaminidase NagZ, results in substantially elevated
susceptibility to the antibiotics, these have been recognized as potential
therapeutic targets. Here, we show a contrasting scenario in Shewanella
oneidensis, in which the homologue of AmpR is absent. Loss of AmpG or NagZ
enhances beta-lactam resistance drastically, whereas other identified major
peptidoglycan recycling enzymes are dispensable. Moreover, our data indicate that
there exists a parallel signal transduction pathway for beta-lactamase induction,
which is independent of either AmpG or NagZ.
PMID- 25136030
TI - Correlation between subchondral bone plate thickness and cartilage degeneration
in osteoarthritis of the ankle.
AB - BACKGROUND: Osteoarthritis (OA) is characterized not only by cartilage
degeneration, but also subchondral bone changes. The subchondral bone plate (SBP)
plays an important role in cartilage metabolism, and elucidation of the
relationship between the SBP and cartilage degeneration would be helpful to
determine the most appropriate treatment strategy for ankle OA. The purpose of
this study was to evaluate the SBP and to compare it with cartilage degeneration
with arthroscopic findings. METHODS: Computed tomography (CT) was used to compare
the thickness of the SBP of 11 ankle OA patients with that of 11 non-ankle OA
patients in 9 areas of the talar dome. The French Society of Arthroscopy (SFA)
grading system was used to analyze the relationship between findings on the
thickness of SBP and on articular cartilage degeneration in ankle OA. RESULTS:
The SBP in ankle OA was significantly thicker than that of the non-OA ankle. The
more severe the articular cartilage degeneration, the thicker the SBP became. The
SBP on the sclerotic trabecular bone was significantly thicker than that on
decreased trabecular bone. The SFA grade for sclerotic subchondral bone was
significantly higher than that for decreased trabecular bone. CONCLUSION: This
study shows that the thickness of SBP and the findings of subchondral bone such
as decreased trabecular bone and sclerosis in CT are related to the cartilage
degeneration of ankle OA, although a small number of patients were analyzed.
LEVEL OF EVIDENCE: Level III, comparative series.
PMID- 25136031
TI - Prognostic value of computed tomography classification systems for intra
articular calcaneus fractures.
AB - BACKGROUND: There are several published computed tomography (CT) classification
systems for calcaneus fractures, each validated by a different standard. The goal
of this study was to measure which system would best predict clinical outcomes as
measured by a widely used and validated musculoskeletal health status
questionnaire. METHODS: Forty-nine patients with isolated intra-articular joint
depression calcaneus fractures more than 2 years after treatment were identified.
All had preoperative CT studies and were treated with open reduction and plate
fixation using a lateral extensile approach. Four different blinded reviewers
classified injuries according to the CT classification systems of Crosby and
Fitzgibbons, Eastwood, and Sanders. Functional outcomes evaluated with a
Musculoskeletal Functional Assessment (MFA). The mean follow-up was 4.3 years.
RESULTS: The mean MFA score was 15.7 (SD = 11.6), which is not significantly
different from published values for midfoot injuries, hindfoot injuries, or both,
1 year after injury (mean = 22.1, SD = 18.4). The classification systems of
Crosby and Fitzgibbons, Eastwood, and Sanders, the number of fragments of the
posterior facet, and payer status were not significantly associated with outcome
as determined by the MFA. The Sanders classification trended toward significance.
Anterior process comminution and surgeon's overall impression of severity were
significantly associated with functional outcome. CONCLUSIONS: The amount of
anterior process comminution was an important determinant of functional outcome
with increasing anterior process comminution significantly associated with
worsened functional outcome (P = .04). In addition, the surgeon's overall
impression of severity of injury was predictive of functional outcome (P = .02),
as determined by MFA. LEVEL OF EVIDENCE: Level III, comparative series.
PMID- 25136032
TI - Re: Role of oncogenic K-Ras in cancer stem cell activation by aberrant Wnt/beta
catenin signaling.
PMID- 25136033
TI - Response.
PMID- 25136034
TI - Manipulating microRNAs to regulate macrophage polarization in gliomas.
PMID- 25136035
TI - Preclinical safety evaluation of human mesenchymal stem cell transplantation in
cerebrum of nonhuman primates.
AB - The efficacy of stem cell transplantation for promoting recovery of patients with
neurological diseases, such as stroke, has been reported in several studies.
However, the safety of the intracerebral transplantation of human mesenchymal
stem cells (hMSCs) remains unclear. The aim of the study was to evaluate the
safety of hMSCs transplanted in cerebrum of Macaca fascicularis and to provide
evidence for clinical application. A total of 24 M fascicularis were assigned to
3 groups randomly: low dose (3.0 * 10(5) cells/kg), high dose (2.5 * 10(6)
cells/kg), and the control (normal saline [NS]). Human mesenchymal stem cells or
NS were injected into each monkey for 2 times, with an interval of 3 weeks. The
injection point was located outside of the right putamen, according to a
stereotactic map and preoperative magnetic resonance imaging of the monkeys.
Animal health, behavior, biophysical and biochemical parameters, and brain
neurological function were routinely monitored over a 6-month period
posttransplantation, and the histopathologic examinations were also performed.
The results showed that local pathologic damage including local tissue necrosis
and inflammation was induced after the injection. The damage of low-dose and high
dose groups was greater than that of the control group, yet over time, the damage
could be repaired gradually. No major hMSCs-associated changes were induced from
other indicators, and the transplantation of hMSCs in monkeys did not affect
total immunoglobulin (Ig) M, total IgG, CD3, CD4, or CD8 values. We therefore
conclude that transplantation of hMSCs to the cerebrum represents a safe
alternative for clinical application of neurological disorders.
PMID- 25136037
TI - Health care provider advice for adolescent tobacco use: results from the 2011
National Youth Tobacco Survey.
AB - BACKGROUND: Health care providers play an important role in promoting tobacco use
abstinence among adolescents. This study aimed to provide nationally
representative data on the prevalence of provider tobacco use screening and
advice delivered to adolescents. Cessation behaviors and correlates of past year
quit attempts among current smokers are also explored. METHODS: Data came from
the 2011 National Youth Tobacco Survey, a nationally representative school-based
survey of adolescents in grades 6 through 12 (n = 18385). Provider screening and
advice were assessed by smoking status and demographic characteristics. Logistic
regression was used to assess the association between advice and past year quit
attempt. RESULTS: The overall prevalence of current tobacco use was 16.6%; 10.8%
were current cigarette smokers (3.6% were established smokers, 7.2% were
nonestablished smokers); 17.3% were former smokers; and 71.9% were never smokers
(22.6% high susceptibility, 77.4% low susceptibility). Among all respondents, the
prevalence of being asked about tobacco use by a health care provider was 32.2%;
the prevalence of being advised to quit or avoid tobacco was 31.4%. Established
smokers were more likely than other groups to report provider assessment of
tobacco use and advice. Receipt of advice was associated with a higher adjusted
odds of having made a past year quit attempt (odds ratio: 1.47, 95% confidence
interval: 1.18-1.82). CONCLUSIONS: Less than one-third of adolescents report
being asked about tobacco use or being advised not to use tobacco. Increased
tobacco use intervention by health care providers is needed to prevent initiation
and increase cessation.
PMID- 25136036
TI - Missed opportunities for HPV vaccination in adolescent girls: a qualitative
study.
AB - OBJECTIVE: The goal of this study was to identify the rationale by
parents/guardians and providers for delaying or administering human
papillomavirus (HPV) vaccination to girls. METHODS: Qualitative interviews were
conducted with parents/guardians accompanying their vaccine-eligible 11- to 17
year-old daughters to medical visits. Interviews were conducted in 1 public
clinic and 3 private practice settings to ascertain why girls did or did not
receive HPV vaccination. Questions probed vaccine decision-making from the point
of view of parents/guardians and providers. RESULTS: A total of 124
parents/guardians and 37 providers participated. The most common reasons parents
reported for not vaccinating their daughters was the lack of a physician
recommendation (44%). Both parents and providers believed that HPV vaccination
provided important health benefits, but the timing of vaccination with relation
to sexual activity was an important theme related to vaccine delay. Providers
with lower self-reported vaccination rates delayed vaccine recommendations in
girls perceived to be at low risk for sexual activity, and several parents
reported that their providers suggested or supported delaying vaccination until
their daughters were older. However, parents/guardians and providers agreed that
predicting the timing of sexual debut was extremely difficult. In contrast,
providers with high vaccination rates presented HPV vaccination as a routine
vaccine with proven safety to prevent cancer, and parents responded positively to
these messages. CONCLUSIONS: Although most parents and providers believe that HPV
vaccination is important, missed opportunities result from assumptions about the
timing of vaccination relative to sexual activity. Routinely recommending HPV
vaccination as cancer prevention to be coadministered with other vaccines at age
11 years can improve vaccination rates.
PMID- 25136039
TI - Pre- and postnatal exposure to parental smoking and allergic disease through
adolescence.
AB - OBJECTIVES: To examine the role of prenatal and postnatal second-hand tobacco
smoke (SHS) exposure on asthma, rhinitis, and eczema development up to 16 years
of age. METHODS: A birth cohort of 4089 children was followed for 16 years.
Information on parental smoking habits, lifestyle factors, and symptoms of
allergic disease was gathered using repeated parental questionnaires. Generalized
estimating equations assessed the overall and age-specific associations between
SHS exposure and allergic disease at ages 1 to 16 years. RESULTS: Exposure to SHS
in utero was associated with an overall elevated risk of developing asthma up to
16 years (odds ratio [OR] = 1.45; 95% confidence interval [CI], 1.15-1.83) but
not for rhinitis or eczema. After additional adjustment for parental smoking
throughout childhood, excess overall risks for asthma remained statistically
significant. Moreover, a dose-dependent pattern with SHS was observed. Exposure
to SHS during infancy was associated with an overall elevated risk of asthma (OR
= 1.23; 95% CI, 1.01-1.51), rhinitis (OR = 1.18; 95% CI, 1.01-1.39), and eczema
(OR = 1.26; 95% CI, 1.09-1.45) up to 16 years. When age-specific associations
were examined, the elevated risks related to SHS exposure in utero or during
infancy were mostly confined to early childhood for asthma and rhinitis, whereas
the excess risk of eczema appeared greatest at later ages. CONCLUSIONS: Our
findings indicate that early SHS exposure, in utero or during infancy, influences
the development of allergic disease up to adolescence. Excess risks for asthma
and rhinitis were seen primarily in early childhood, whereas those for eczema
occurred at later ages.
PMID- 25136040
TI - HIV transmission through breastfeeding: still possible in developed countries.
AB - We describe here the case of a 13-month-old boy who acquired HIV infection
postnatally through breastfeeding in a developed country in 2012. His mother had
regular pregnancy follow-up and was found to be seronegative for HIV on 2
consecutive screening tests (during pregnancy and just after delivery). However,
1 year later, diagnosis of HIV infection arose in both of them after a pediatric
emergency department visit for bronchitis when unexplained hepatosplenomegaly and
inflammatory syndrome were noted. The negative maternal viral load found just
after delivery confirmed that the mother's seroconversion occurred postnatally,
which allowed for active HIV transmission during lactation and lack of the
efficient preventive measures that have implemented in Belgium for years. We
discuss this uncommon but still existing mode of HIV transmission in
industrialized countries and highlight the importance of implementing new
targeted health education interventions in addition to constant clinicians'
awareness.
PMID- 25136041
TI - Mechanical ventilation for a child with quadriplegia.
AB - Parents generally have the right to make medical decisions for their children.
This right can be challenged when the parents' decision seems to go against the
child's interests. The toughest such decisions are for a child who will survive
with physical and neurocognitive impairments. We discuss a case of a 5-year-old
boy who suffered a spinal injury as a result of a motor vehicle accident and
whose father requests discontinuation of life support. Many experts recommend a
"trial of therapy" to clarify both prognosis and quality of life. The key ethical
question, then, is not whether to postpone a decision to forego mechanical
ventilation. Instead, the key question is how long to wait. Parents should be
allowed time to see what life will be like for themselves and for their child.
Most of the time, life turns out better than they might have imagined. Comments
are provided by 2 pediatric intensivists, Drs William Novotny and Ronald Perkin
of East Carolina University, and by a specialist in rehabilitation, Dr Debjani
Mukherjee of the Rehabilitation Institute of Chicago.
PMID- 25136038
TI - Vaccine message framing and parents' intent to immunize their infants for MMR.
AB - BACKGROUND AND OBJECTIVE: Emphasizing societal benefits of vaccines has been
linked to increased vaccination intentions in adults. It is unclear if this
pattern holds for parents deciding whether to vaccinate their children. The
objective was to determine whether emphasizing the benefits of measles-mumps
rubella (MMR) vaccination directly to the vaccine recipient or to society
differentially impacts parents' vaccine intentions for their infants. METHODS: In
a national online survey, parents (N = 802) of infants <12 months old were
randomly assigned to receive 1 of 4 MMR vaccine messages: (1) the Centers for
Disease Control and Prevention Vaccine Information Statement (VIS), (2) VIS and
information emphasizing the MMR vaccine's benefits to the child, (3) VIS and
information emphasizing societal benefits, or (4) VIS and information emphasizing
benefits both to the child and society. Parents reported their likelihood of
vaccinating their infants for MMR on a response scale of 0 (extremely unlikely)
to 100 (extremely likely). RESULTS: Compared with the VIS-only group (mean
intention = 86.3), parents reported increased vaccine intentions for their
infants when receiving additional information emphasizing the MMR vaccine's
benefits either directly to the child (mean intention = 91.6, P = .01) or to both
the child and society (mean intention = 90.8, P = .03). Emphasizing the MMR
vaccine's benefits only to society did not increase intentions (mean intention =
86.4, P = .97). CONCLUSIONS: We did not see increases in parents' MMR vaccine
intentions for their infants when societal benefits were emphasized without
mention of benefits directly to the child. This finding suggests that providers
should emphasize benefits directly to the child. Mentioning societal benefits
seems to neither add value to, nor interfere with, information highlighting
benefits directly to the child.
PMID- 25136042
TI - Neonatal vitamin K refusal and nonimmunization.
AB - BACKGROUND: Neonatal Vitamin K prophylaxis is an effective intervention for
reducing vitamin K deficiency bleeding. A recently published report of parental
refusal of vitamin K prompted an investigation of the prevalence and
characteristics of this group, and exploration of whether these same parents were
likely to subsequently refuse immunization for their children. METHODS: We
conducted a retrospective population-based cohort study of all infants born in
Alberta between 2006 and 2012 by using linkage of administrative health data.
Risk factors for vitamin K refusal were determined by using Poisson regression.
The association between vitamin K refusal and nonimmunization was assessed using
relative risk. RESULTS: Among the 282378 children in the cohort, 99.7% received
vitamin K and 0.3% declined. Midwife-assisted deliveries were more likely to be
associated with vitamin K refusal compared with physician-attended delivery (risk
ratio 8.4, 95% confidence interval [CI] 6.5-11.0). Planned home delivery (risk
ratio 4.9, CI 3.8-6.4) or delivery in a birth center (risk ratio 3.6, CI 2.3-5.6)
were more likely to result in decline of vitamin K compared with hospital
delivery. Vitamin K refusal was associated with a 14.6 (CI 13.9-15.3) higher
relative risk of having no recommended childhood vaccines at 15 months.
CONCLUSIONS: This is the first population-based study to characterize parents who
are likely to decline vitamin K for their infants and whose children are likely
to be unimmunized. These findings enable earlier identification of high-risk
parents and provide an opportunity to enact strategies to increase uptake of
vitamin K and childhood immunizations.
PMID- 25136043
TI - Automated urinalysis and urine dipstick in the emergency evaluation of young
febrile children.
AB - OBJECTIVE: The performance of automated flow cytometric urinalysis is not well
described in pediatric urinary tract infection. We sought to determine the
diagnostic performance of automated cell counts and emergency department point-of
care (POC) dipstick urinalyses in the evaluation of young febrile children.
METHODS: We prospectively identified a convenience sample of febrile pediatric
emergency department patients <48 months of age who underwent urethral
catheterization to obtain POC and automated urinalyses and urine culture.
Receiver operating characteristic analyses were performed and diagnostic indices
were calculated for POC dipstick and automated cell counts at different
cutpoints. RESULTS: Of 342 eligible children, 42 (12%) had urinary bacterial
growth >= 50000/mL. The areas under the receiver operating characteristic curves
were: automated white blood cell count, 0.97; automated bacterial count, 0.998;
POC leukocyte esterase, 0.94; and POC nitrite, 0.76. Sensitivities and
specificities were 86% and 98% for automated leukocyte counts >= 100/MUL and 98%
and 98% for bacterial counts >= 250/MUL. POC urine dipstick with >= 1+ leukocyte
esterase or positive nitrite had a sensitivity of 95% and a specificity of 98%.
Combinations of white blood cell and bacterial counts did not outperform
bacterial counts alone. CONCLUSIONS: Automated leukocyte and bacterial counts
performed well in the diagnosis of urinary tract infection in these febrile
pediatric patients, but POC dipstick may be an acceptable alternative in clinical
settings that require rapid decision-making.
PMID- 25136044
TI - Establishing benchmarks for the hospitalized care of children with asthma,
bronchiolitis, and pneumonia.
AB - BACKGROUND AND OBJECTIVES: Asthma, pneumonia, and bronchiolitis are the leading
causes of admission for pediatric patients; however, the lack of accepted
benchmarks is a barrier to quality improvement efforts. Using data from children
hospitalized with asthma, bronchiolitis, or pneumonia, the goals of this study
were to: (1) measure the 2012 performance of freestanding children's hospitals
using clinical quality indicators; and (2) construct achievable benchmarks of
care (ABCs) for the clinical quality indicators. METHODS: This study was a cross
sectional trial using the Pediatric Health Information System database. Patient
inclusions varied according to diagnosis: asthma (International Classification of
Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 493.0-493.92)
from 2 to 18 years of age; bronchiolitis (ICD-9-CM codes 466.11 and 466.19) from
2 months to 2 years of age; and pneumonia (ICD-9-CM codes 480-486, 487.0) from 2
months to 18 years of age. ABC methods use the best-performing hospitals that
comprise at least 10% of the total population to compute the benchmark. RESULTS:
Encounters from 42 hospitals included: asthma, 22186; bronchiolitis, 14882; and
pneumonia, 12983. Asthma ABCs include: chest radiograph utilization, 24.5%;
antibiotic administration, 6.6%; and ipratropium bromide use >2 days, 0%.
Bronchiolitis ABCs include: chest radiograph utilization, 32.4%; viral testing,
0.6%; antibiotic administration, 18.5%; bronchodilator use >2 days, 11.4%; and
steroid use, 6.4%. Pneumonia ABCs include: complete blood cell count utilization,
28.8%; viral testing, 1.5%; initial narrow-spectrum antibiotic use, 60.7%;
erythrocyte sedimentation rate, 3.5%; and C-reactive protein, 0.1%. CONCLUSIONS:
We report achievable benchmarks for inpatient care for asthma, bronchiolitis, and
pneumonia. The establishment of national benchmarks will drive improvement at
individual hospitals.
PMID- 25136045
TI - Pharmacokinetics of fluoride in toddlers after application of 5% sodium fluoride
dental varnish.
AB - The prevalence of dental caries (tooth decay) among preschool children is
increasing, driven partially by an earlier age of onset of carious lesions. The
American Academy of Pediatrics recommends application of 5% sodium fluoride
varnish at intervals increasing with caries risk status, as soon as teeth are
present. However, the varnishes are marketed for treatment of tooth sensitivity
and are regulated as medical devices rather than approved by the US Food and Drug
Administration for prevention of dental caries (tooth decay). The objective of
this research is to examine the safety of use in toddlers by characterizing the
absorption and distribution profile of a currently marketed fluoride varnish. We
measured urinary fluoride for 5 hours after application of fluoride varnish to
teeth in 6 toddlers aged 12 to 15 months. Baseline levels were measured on a
separate day. The urine was extracted from disposable diapers, measured by rapid
diffusion, and extrapolated to plasma levels. The mean estimated plasma fluoride
concentration was 13 MUg/L (SD, 9 MUg/L) during the baseline visit and 21 MUg/L
(SD, 8 MUg/L) during the 5 hours after treatment. Mean estimated peak plasma
fluoride after treatment was 57 MUg/L (SD, 22 MUg/L), and 20 MUg/kg (SD, 4 MUg/L)
was retained on average. Retained fluoride was 253 times lower than the acute
toxic dose of 5 mg/kg. Mean plasma fluoride after placement of varnish was within
an SD of control levels. Occasional application of fluoride varnish following
American Academy of Pediatrics guidance is safe for toddlers.
PMID- 25136047
TI - Delivering tobacco control interventions in adolescent health care visits: time
for action.
PMID- 25136046
TI - Impact of a pertussis epidemic on infant vaccination in Washington state.
AB - BACKGROUND AND OBJECTIVES: Washington State experienced a pertussis epidemic from
October 2011 to December 2012. There was wide variation in incidence by county.
The objectives of this study were to determine how the pertussis epidemic
affected infant vaccination in Washington State and whether the incidence in
counties modified this effect. METHODS: We conducted an ecologic before-after
study to compare the proportion of infants up to date (UTD) with a pertussis
containing vaccine at time points before (September 30, 2011), during (September
30, 2012), and after (September 30, 2013) the epidemic. Children aged 3 to 8
months enrolled in the Washington State Immunization Information System with
documented county of residence were included. UTD status was determined as >= 1,
>= 2, or >= 3 doses of a pertussis-containing vaccine at ages 3, 5, and 7 months,
respectively. Generalized linear models with extension to the binomial family and
clustered robust standard errors were used to examine differences in the
proportion of UTD infants between preepidemic and either epidemic or postepidemic
points. The potential modifying effect of pertussis incidence by county was
examined. RESULTS: We found no significant difference in statewide UTD status
with a pertussis-containing vaccine between preepidemic and either epidemic
(absolute difference 2.1%; 95% confidence interval, -1.6 to 5.9) or postepidemic
(absolute difference 0.2%; 95% confidence interval, -4.0 to 4.5) time points.
There was no significant modification by county pertussis incidence. There was
wide variation in the absolute difference in UTD status across counties.
CONCLUSIONS: A statewide pertussis epidemic does not appear to have significantly
changed the proportion of infants who were UTD with a pertussis-containing
vaccine.
PMID- 25136048
TI - High-dose vitamin A with vaccination after 6 months of age: a randomized trial.
AB - BACKGROUND: The World Health Organization recommends vitamin A supplementation
(VAS) at routine vaccination contacts after 6 months of age based on the
assumption that it reduces mortality by 24%. The policy has never been evaluated
in randomized controlled trials for its effect on overall mortality. We conducted
a randomized double-blind trial to evaluate the effect of VAS with vaccines.
METHODS: We randomized children aged 6 to 23 months 1:1 to VAS (100000 IU if aged
6-11 months, 200000 IU if aged 12-23 months) or placebo at vaccination contacts
in Guinea-Bissau. Mortality rates were compared in Cox proportional-hazards
models overall, and by gender and vaccine. RESULTS: Between August 2007 and
November 2010, 7587 children were enrolled. Within 6 months of follow-up 80
nonaccident deaths occurred (VAS: 38; placebo: 42). The mortality rate ratio
(MRR) comparing VAS versus placebo recipients was 0.91 (95% confidence interval
0.59-1.41) and differed significantly between boys (MRR 1.92 [0.98-3.75]) and
girls (MRR 0.45 [0.24-0.87]) (P = .003 for interaction between VAS and gender).
At enrollment, 42% (3161/7587) received live measles vaccine, 29% (2154/7587)
received inactivated diphtheria-tetanus-pertussis-containing vaccines, and 21%
(1610/7587) received both live and inactivated vaccines. The effect of VAS did
not differ by vaccine group. CONCLUSIONS: This is the first randomized controlled
trial to assess the effect of the policy on overall mortality. VAS had no overall
effect, but the effect differed significantly by gender. More trials to ensure an
optimal evidence-based vitamin A policy are warranted.
PMID- 25136049
TI - Pertussis resurgence and vaccine uptake: implications for reducing vaccine
hesitancy.
PMID- 25136050
TI - Long-term study of a quadrivalent human papillomavirus vaccine.
AB - BACKGROUND: We present a long-term safety, immunogenicity, and effectiveness
study of a quadrivalent human papillomavirus (HPV4) vaccine. METHODS: Sexually
naive boys and girls aged 9 to 15 years (N = 1781) were assigned (2:1) to receive
HPV4 vaccine or saline placebo at day 1 and months 2 and 6. At month 30, the
placebo group (n = 482) received HPV4 vaccine following the same regimen and both
cohorts were followed through month 96. Subjects >= 16 years were eligible for
effectiveness evaluations. The primary objective was to evaluate the long-term
anti-HPV6/11/16/18 serological levels. The secondary objective was to estimate
vaccine effectiveness against HPV6/11/16/18-related persistent infection or
disease. RESULTS: For each of the HPV4 vaccine types, vaccination-induced anti
HPV response persisted through month 96. Among 429 subjects who received HPV4
vaccine at a mean age of 12, none developed HPV6/11/16/18-related disease or
persistent infection of >= 12 months' duration. Acquisition of new sexual
partners (among those >= 16 years) was ~1 per year. Subjects receiving HPV4
vaccine at month 30 (mean age 15 years) had a similar baseline rate of
seropositivity to >= 1 of the 4 HPV types to those vaccinated at day 1 (mean age
12 years; 1.9% [9 of 474] vs 1.7% [20 of 1157]); however, 4 of the 9 subjects
vaccinated at the later age were seropositive to 3 vaccine types, indicating
previous HPV exposure. No new significant serious adverse events were observed
for 8 years postvaccination in both genders. CONCLUSIONS: When administered to
adolescents, the HPV4 vaccine demonstrated durability in clinically effective
protection and sustained antibody titers over 8 years.
PMID- 25136051
TI - Changing trends of childhood disability, 2001-2011.
AB - BACKGROUND: Over the past half century the prevalence of childhood disability
increased dramatically, coupled with notable increases in the prevalence of
mental health and neurodevelopmental conditions. This study provides a detailed
assessment of recent trends in childhood disability in relation to health
conditions and sociodemographic factors. METHODS: Secondary data analysis of
National Health Interview Survey (NHIS) datasets 2001-2002, 2004-2005, 2007-2008,
and 2010-2011 (N = 198888) was conducted to calculate the prevalence, rate of
change, severity, and sociodemographic disparities of parent-reported childhood
disability. RESULTS: The prevalence of childhood disability has continued to
increase, growing by 15.6% between 2001-2002 and 2010-2011. Nearly 6 million
children were considered disabled in 2010-2011. Children living in poverty
experienced the highest rates of disability, 102.6 cases per 1000 population in
2010-2011, but unexpectedly, children living in households with incomes >= 400%
above the federal poverty level experienced the largest increase (28.4%) over
this 10-year period. The percentage of disability cases related to any physical
health condition declined 11.8% during the decade, whereas cases related to any
neurodevelopmental or mental health condition increased by 20.9%. CONCLUSIONS:
Over the past decade, parent-reported childhood disability steadily increased. As
childhood disability due to physical conditions declined, there was a large
increase in disabilities due to neurodevelopmental or mental health problems. For
the first time since the NHIS began tracking childhood disability in 1957, the
rise in reported prevalence is disproportionately occurring among socially
advantaged families. This unexpected finding highlights the need to better
understand the social, medical, and environmental factors influencing parent
reports of childhood disability.
PMID- 25136053
TI - Prevalence of human papillomavirus and Epstein-Barr virus in salivary gland
diseases.
AB - OBJECTIVE: The roles of human papillomavirus (HPV) and Epstein-Barr virus (EBV)
in head and neck neoplasms have been well reported, but little is known about
their relationship with salivary gland tumours. This study investigated the
presence of HPV and EBV in salivary gland diseases. METHODS: The presence of HPV
16/18 and EBV was analysed in archival pathological specimens collected from
patients who had undergone surgery for salivary gland diseases. HPV 16/18 DNA was
detected using nested polymerase chain reaction (PCR) and further confirmed with
immunohistochemistry. EBV DNA was detected using real-time PCR. RESULTS: A total
of 61 pathological specimens were examined: 39.5% (15/38) of pleomorphic
adenomas, 33.3% (3/9) of Warthin's tumours, 33.3% (one of 3) of mucoepidermoid
carcinomas, and 25.0% (one of 4) of benign lymphoepithelial lesions were positive
for high-risk HPV 16/18. Only two Warthin's tumours were positive for EBV.
CONCLUSION: The infectious nature of salivary gland neoplasms was revealed by the
high prevalence of HPV infection, and the specific presence of EBV in Warthin's
tumours, suggesting a potential role for HPV and EBV in salivary gland diseases.
PMID- 25136054
TI - MOG-IgG serological status matters in paediatric ADEM.
PMID- 25136055
TI - The autosomal dominant spinocerebellar ataxias: emerging mechanistic themes
suggest pervasive Purkinje cell vulnerability.
AB - The spinocerebellar ataxias are a genetically heterogeneous group of disorders
with clinically overlapping phenotypes arising from Purkinje cell degeneration,
cerebellar atrophy and varying degrees of degeneration of other grey matter
regions. For 22 of the 32 subtypes, a genetic cause has been identified. While
recurring themes are emerging, there is no clear correlation between the clinical
phenotype or penetrance, the type of genetic defect or the category of the
disease mechanism, or the neuronal types involved beyond Purkinje cells. These
phenomena suggest that cerebellar Purkinje cells may be a uniquely vulnerable
neuronal cell type, more susceptible to a wider variety of genetic/cellular
insults than most other neuron types.
PMID- 25136056
TI - One-year dynamic MRI follow-up after vaginal mesh repair: evaluation of clinical,
radiological, and quality-of-life results.
AB - BACKGROUND: Pelvic organ prolapse (POP) is a common disorder in elderly women
often surgically repaired with alloplastic meshes; yet knowledge of the pelvic
floor behavior and multi-compartment defects postoperatively is scarce. PURPOSE:
To evaluate the 1-year outcome after mesh repair in patients with POP using
clinical examination (CE), dynamic magnetic resonance imaging (dMRI), and the
prolapse quality-of-life (P-QOL) questionnaire. MATERIAL AND METHODS: A
prospective observational study was conducted of 69 women undergoing pelvic mesh
surgery. Clinical examination, dMRI, and the P-QOL questionnaire were applied
before and after surgery to evaluate POP. Mean outcome measures were POP outcome
as determined on clinical and dMRI examinations and its impact on quality of
life. Statistical results were obtained with SPSS version 15.0. ANOVA was used to
compare pre-/postsurgical quality of life data. RESULTS: Sixty-nine women (mean
age, 64.75 years; BMI, 26.75 kg/m(2); postmenopausal, 89.2%) were recruited and
treated with Seratom(r) or PerigeeTM mesh implants. A significant improvement in
the position of bladder neck, vaginal vault/uterus, pouch of Douglas, and rectum
was found 12 weeks and 1 year after surgery using POP-Q scale and dMRI. Advanced
cystoceles and enteroceles seem underestimated by CE using the POP-Q system
compared to dMRI results (P = 0.003 and P < 0.001), vice versa dMRI overestimated
POP compared to CE. Sixty-four women completed the P-QOL questionnaire,
presenting reduced quality of life before surgery which improves postsurgically.
Prolapse impact and physical, social, and role limitations correlated strongest
with a low quality of life (P < 0.001). CONCLUSION: The 1-year follow-up after
mesh repair showed statistical and clinical improvement for all tools employed.
dMRI seems a reliable tool for simultaneous assessment of defects in all three
compartments, but tends to overestimate POP compared to clinical examination.
PMID- 25136057
TI - Using party horns to test respiratory function in patients with dementia.
AB - This study assessed the utility of party horns for quick, simple respiratory
function testing in 66 inpatients with dementia to maintain safe eating activity.
Relationships of forced vital capacity (FVC) to Mini-Mental State Examination
(MMSE) score and complete extension when blowing 40- and 80-cm party horns were
examined. The FVC differed significantly by both MMSE score (P = .000) and party
horn score (P = .000). Significant differences in FVC were found between groups
categorized by MMSE score and in groups categorized by the ability to extend both
party horns. Multiple regression analyses performed on possible FVC indicators
identified a significant correlation for the party horn examination (regression
coefficient: .562). Breathing is always coordinated with swallowing. Party horns
seem highly effective as a simple tool for testing respiratory function in
patients with early-stage dementia, and the ability to offer breathing
rehabilitation for patients in need is likely to result in safer eating activity.
PMID- 25136058
TI - Does laboratory testing decrease during scheduled downtime of an electronic order
entry system?
PMID- 25136059
TI - Acute versus sub-acute care beds: should Australia invest in community beds at
the expense of hospital beds?
PMID- 25136060
TI - Branching out in roots: uncovering form, function, and regulation.
AB - Root branching is critical for plants to secure anchorage and ensure the supply
of water, minerals, and nutrients. To date, research on root branching has
focused on lateral root development in young seedlings. However, many other
programs of postembryonic root organogenesis exist in angiosperms. In cereal
crops, the majority of the mature root system is composed of several classes of
adventitious roots that include crown roots and brace roots. In this Update, we
initially describe the diversity of postembryonic root forms. Next, we review
recent advances in our understanding of the genes, signals, and mechanisms
regulating lateral root and adventitious root branching in the plant models
Arabidopsis (Arabidopsis thaliana), maize (Zea mays), and rice (Oryza sativa).
While many common signals, regulatory components, and mechanisms have been
identified that control the initiation, morphogenesis, and emergence of new
lateral and adventitious root organs, much more remains to be done. We conclude
by discussing the challenges and opportunities facing root branching research.
PMID- 25136061
TI - Radial transport of nutrients: the plant root as a polarized epithelium.
AB - In higher plants, roots acquire water and soil nutrients and transport them
upward to their aerial parts. These functions are closely related to their
anatomical structure; water and nutrients entering the root first move radially
through several concentric layers of the epidermis, cortex, and endodermis before
entering the central cylinder. The endodermis is the innermost cortical cell
layer that features rings of hydrophobic cell wall material called the Casparian
strips, which functionally resemble tight junctions in animal epithelia. Nutrient
uptake from the soil can occur through three different routes that can be
interconnected in various ways: the apoplastic route (through the cell wall), the
symplastic route (through cellular connections), and a coupled trans-cellular
route (involving polarized influx and efflux carriers). This Update presents
recent advances in the radial transport of nutrients highlighting the coupled
trans-cellular pathway and the roles played by the endodermis as a barrier.
PMID- 25136062
TI - Distinct signaling mechanisms in multiple developmental pathways by the SCRAMBLED
receptor of Arabidopsis.
AB - SCRAMBLED (SCM), a leucine-rich repeat receptor-like kinase in Arabidopsis
(Arabidopsis thaliana), is required for positional signaling in the root
epidermis and for tissue/organ development in the shoot. To further understand
SCM action, we generated a series of kinase domain variants and analyzed their
ability to complement scm mutant defects. We found that the SCM kinase domain,
but not kinase activity, is required for its role in root epidermal patterning,
supporting the view that SCM is an atypical receptor kinase. We also describe a
previously uncharacterized role for SCM in fruit dehiscence, because mature
siliques from scm mutants fail to open properly. Interestingly, the kinase domain
of SCM appears to be dispensable for this developmental process. Furthermore, we
found that most of the SCM kinase domain mutations dramatically inhibit
inflorescence development. Because this process is not affected in scm null
mutants, it is likely that SCM acts redundantly to regulate inflorescence size.
The importance of distinct kinase residues for these three developmental
processes provides an explanation for the maintenance of the conserved kinase
domain in the SCM protein, and it may generally explain its conservation in other
atypical kinases. Furthermore, these results indicate that individual leucine
rich repeat receptor-like kinases may participate in multiple pathways using
distinct signaling mechanisms to mediate diverse cellular communication events.
PMID- 25136063
TI - Activity of the brassinosteroid transcription factors BRASSINAZOLE RESISTANT1 and
BRASSINOSTEROID INSENSITIVE1-ETHYL METHANESULFONATE-SUPPRESSOR1/BRASSINAZOLE
RESISTANT2 blocks developmental reprogramming in response to low phosphate
availability.
AB - Plants feature remarkable developmental plasticity, enabling them to respond to
and cope with environmental cues, such as limited availability of phosphate, an
essential macronutrient for all organisms. Under this condition, Arabidopsis
(Arabidopsis thaliana) roots undergo striking morphological changes, including
exhaustion of the primary meristem, impaired unidirectional cell expansion, and
elevated density of lateral roots, resulting in shallow root architecture. Here,
we show that the activity of two homologous brassinosteroid (BR) transcriptional
effectors, BRASSINAZOLE RESISTANT1 (BZR1) and BRASSINOSTEROID INSENSITIVE1-ETHYL
METHANESULFONATE-SUPPRESSOR1 (BES1)/BZR2, blocks these responses, consequently
maintaining normal root development under low phosphate conditions without
impacting phosphate homeostasis. We show that phosphate deprivation shifts the
intracellular localization of BES1/BZR2 to yield a lower nucleus-to-cytoplasm
ratio, whereas replenishing the phosphate supply reverses this ratio within
hours. Phosphate deprivation reduces the expression levels of BR biosynthesis
genes and the accumulation of the bioactive BR 28-norcastasterone. In agreement,
low and high BR levels sensitize and desensitize root response to this adverse
condition, respectively. Hence, we propose that the environmentally controlled
developmental switch from deep to shallow root architecture involves reductions
in BZR1 and BES1/BZR2 levels in the nucleus, which likely play key roles in plant
adaptation to phosphate-deficient environments.
PMID- 25136064
TI - Efficacy of electronic cigarettes for smoking cessation.
AB - OBJECTIVE: To review data demonstrating effective smoking cessation with
electronic cigarettes (e-cigarettes). DATA SOURCES: A literature search of
MEDLINE/PubMed (1946-March 2014) was performed using the search terms e
cigarettes, electronic cigarettes, and smoking cessation. Additional references
were identified from a review of literature citations. STUDY SELECTION AND DATA
EXTRACTION: All English-language clinical studies assessing efficacy of e
cigarettes compared with baseline, placebo, or other pharmacological methods to
aid in withdrawal symptoms, smoking reduction, or cessation were evaluated. DATA
SYNTHESIS: A total of 6 clinical studies were included in the review. In small
studies, e-cigarettes significantly decreased desire to smoke, number of
cigarettes smoked per day, and exhaled carbon monoxide levels. Symptoms of
nicotine withdrawal and adverse effects were variable. The most common adverse
effects were nausea, headache, cough, and mouth/throat irritation. Compared with
nicotine patches, e-cigarettes were associated with fewer adverse effects and
higher adherence. Most studies showed a significant decrease in cigarette use
acutely; however, long-term cessation was not sustained at 6 months. CONCLUSIONS:
There is limited evidence for the effectiveness of e-cigarettes in smoking
cessation; however, there may be a place in therapy to help modify smoking habits
or reduce the number of cigarettes smoked. Studies available provided different
administration patterns such as use while smoking, instead of smoking, or as
needed. Short-term studies reviewed were small and did not necessarily evaluate
cessation with a focus on parameters associated with cessation withdrawal
symptoms. Though long-term safety is unknown, concerns regarding increased
poisoning exposures among adults in comparison with cigarettes are alarming.
PMID- 25136065
TI - Albiglutide: a new GLP-1 receptor agonist for the treatment of type 2 diabetes.
AB - OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of
albiglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in type 2
diabetes (T2D). DATA SOURCES: A MEDLINE search (1950-June 2014) was conducted
using the keyword albiglutide. References were reviewed to identify additional
sources. STUDY SELECTION AND DATA EXTRACTION: Articles evaluating
pharmacokinetics, pharmacodynamics, safety, or efficacy of albiglutide were
included. DATA SYNTHESIS: Albiglutide is a long-acting GLP-1 RA that lowers
glycosylated hemoglobin (A1C) and reduces weight by stimulating glucose-dependent
insulin secretion, suppressing glucagon secretion, delaying gastric emptying, and
promoting satiety. Albiglutide has a long half-life as a result of resistance to
degradation by dipeptidyl peptidase-4 and fusion to albumin, thus allowing once
weekly dosing. Albiglutide has been studied as monotherapy and add-on therapy to
metformin, sulfonylureas, thiazolidinediones, insulin glargine, and varying
combinations of these agents. Clinical studies have shown albiglutide to be
superior to placebo, sitagliptin, and glimepiride and noninferior to insulin
glargine and insulin lispro at reducing A1C in T2D patients, with A1C changes
from baseline ranging from -0.55% to -0.9%. Noninferiority was not achieved when
compared to liraglutide and pioglitazone. Weight changes ranged from +0.28 to
1.21 kg. The most common side effects are upper-respiratory-tract infections,
diarrhea, nausea, and injection-site reactions. CONCLUSION: Albiglutide is the
fourth GLP-1 RA approved in the United States. Advantages include once-weekly
dosing and fewer gastrointestinal side effects compared with liraglutide, but it
is less effective at reducing A1C and weight compared to liraglutide. It has not
been compared head to head with other GLP-1 RAs.
PMID- 25136068
TI - Mycoplasma hyorhinis infection promotes NF-kappaB-dependent migration of gastric
cancer cells.
AB - Chronic infection of Mycoplasma hyorhinis (M. hyorhinis) has been postulated to
be associated with several types of cancer, but its effect on patients' survival
and host factors mediating its infection remain unclear. Herein, we demonstrated
that M. hyorhinis p37 protein expression in gastric cancer tissues predicts poor
survival and associates with metastasis. M. hyorhinis infects mammalian cells and
promotes gastric cancer cell invasiveness via its membrane protein p37.
Synthesized peptide corresponding to the N-terminus of p37 prevents M. hyorhinis
infection. Host Annexin A2 (ANXA2) interacts with the N-terminus of p37. In
addition, EGFR forms a complex with p37 and ANXA2, and is required for M.
hyorhinis-induced phosphorylation and membrane recruitment of ANXA2. M. hyorhinis
infection is inhibited by siRNA-mediated knockdown of ANXA2 or EGFR, but is
enhanced by expression of ectopic ANXA2 or EGFR. Downstream of ANXA2 and EGFR,
the NF-kappaB pathway is activated and mediates M. hyorhinis-driven cell
migration. In conclusion, our study unveils the effect of M. hyorhinis infection
on gastric cancer survival and uncovers the mechanisms by which M. hyorhinis
infects mammalian cells and promotes cancer cell migration.
PMID- 25136067
TI - PRMT7 induces epithelial-to-mesenchymal transition and promotes metastasis in
breast cancer.
AB - Epithelial-to-mesenchymal transition (EMT) enables metastasis. E-cadherin loss is
a hallmark of EMT, but there remains an incomplete understanding of the
epigenetics of this process. The protein arginine methyltransferase PRMT7
functions in various physiologic processes, including mRNA splicing, DNA repair,
and neural differentiation, but its possible roles in cancer and metastasis have
not been explored. In this report, we show that PRMT7 is expressed at higher
levels in breast carcinoma cells and that elevated PRMT7 mediates EMT and
metastasis. PRMT7 could inhibit the expression of E-cadherin by binding to its
proximal promoter in a manner associated with altered histone methylation,
specifically with elevated H4R3me2s and reduced H3K4me3, H3Ac, and H4Ac, which
occurred at the E-cadherin promoter upon EMT induction. Moreover, PRMT7
interacted with YY1 and HDAC3 and was essential to link these proteins to the E
cadherin promoter. Silencing PRMT7 restored E-cadherin expression by repressing
H4R3me2s and by increasing H3K4me3 and H4Ac, attenuating cell migration and
invasion in MDA-MB-231 breast cancer cells. Overall, our results define PRMT7 as
an inducer of breast cancer metastasis and present the opportunity for applying
PRMT7-targeted therapeutics to treat highly invasive breast cancers.
PMID- 25136066
TI - AXL mediates resistance to cetuximab therapy.
AB - The EGFR antibody cetuximab is used to treat numerous cancers, but intrinsic and
acquired resistance to this agent is a common clinical outcome. In this study, we
show that overexpression of the oncogenic receptor tyrosine kinase AXL is
sufficient to mediate acquired resistance to cetuximab in models of non-small
cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC), where
AXL was overexpressed, activated, and tightly associated with EGFR expression in
cells resistant to cetuximab (Ctx(R) cells). Using RNAi methods and novel AXL
targeting agents, we found that AXL activation stimulated cell proliferation,
EGFR activation, and MAPK signaling in Ctx(R) cells. Notably, EGFR directly
regulated the expression of AXL mRNA through MAPK signaling and the transcription
factor c-Jun in Ctx(R) cells, creating a positive feedback loop that maintained
EGFR activation by AXL. Cetuximab-sensitive parental cells were rendered
resistant to cetuximab by stable overexpression of AXL or stimulation with EGFR
ligands, the latter of which increased AXL activity and association with the
EGFR. In tumor xenograft models, the development of resistance following
prolonged treatment with cetuximab was associated with AXL hyperactivation and
EGFR association. Furthermore, in an examination of patient-derived xenografts
established from surgically resected HNSCCs, AXL was overexpressed and activated
in tumors that displayed intrinsic resistance to cetuximab. Collectively, our
results identify AXL as a key mediator of cetuximab resistance, providing a
rationale for clinical evaluation of AXL-targeting drugs to treat cetuximab
resistant cancers. Cancer Res; 74(18); 5152-64. (c)2014 AACR.
PMID- 25136069
TI - Epigenetic states of cells of origin and tumor evolution drive tumor-initiating
cell phenotype and tumor heterogeneity.
AB - A central confounding factor in the development of targeted therapies is tumor
cell heterogeneity, particularly in tumor-initiating cells (TIC), within
clinically identical tumors. Here, we show how activation of the Sonic Hedgehog
(SHH) pathway in neural stem and progenitor cells creates a foundation for tumor
cell evolution to heterogeneous states that are histologically indistinguishable
but molecularly distinct. In spontaneous medulloblastomas that arise in Patched
(Ptch)(+/-) mice, we identified three distinct tumor subtypes. Through cell type
specific activation of the SHH pathway in vivo, we determined that different
cells of origin evolved in unique ways to generate these subtypes. Moreover, TICs
in each subtype had distinct molecular and cellular phenotypes. At the bulk tumor
level, the three tumor subtypes could be distinguished by a 465-gene signature
and by differential activation levels of the ERK and AKT pathways. Notably, TICs
from different subtypes were differentially sensitive to SHH or AKT pathway
inhibitors, highlighting new mechanisms of resistance to targeted therapies. In
summary, our results show how evolutionary processes act on distinct cells of
origin to contribute to tumoral heterogeneity, at both bulk tumor and TIC levels.
PMID- 25136072
TI - Proposal for a synthetic lethality therapy using the paralog dependence of cancer
cells--response.
PMID- 25136070
TI - ACVR1 mutations in DIPG: lessons learned from FOP.
AB - Whole-genome sequencing studies have recently identified a quarter of cases of
the rare childhood brainstem tumor diffuse intrinsic pontine glioma to harbor
somatic mutations in ACVR1. This gene encodes the type I bone morphogenic protein
receptor ALK2, with the residues affected identical to those that, when mutated
in the germline, give rise to the congenital malformation syndrome fibrodysplasia
ossificans progressiva (FOP), resulting in the transformation of soft tissue into
bone. This unexpected link points toward the importance of developmental biology
processes in tumorigenesis and provides an extensive experience in mechanistic
understanding and drug development hard-won by FOP researchers to pediatric
neurooncology. Here, we review the literature in both fields and identify
potential areas for collaboration and rapid advancement for patients of both
diseases.
PMID- 25136073
TI - A synthetic lethality-based strategy to treat cancers harboring a genetic
deficiency in the chromatin remodeling factor BRG1--letter.
PMID- 25136075
TI - Mouse models of human cancer.
AB - The Helmholtz Alliance Preclinical Comprehensive Cancer Center (PCCC;
www.helmholtz-pccc.de) hosted the "1st International Kloster Seeon Meeting on
Mouse Models of Human Cancer" in the Seeon monastery (Germany) from March 8 to
11, 2014. The meeting focused on the development and application of novel mouse
models in tumor research and high-throughput technologies to overcome one of the
most critical bottlenecks in translational bench-to-bedside tumor biology
research. Moreover, the participants discussed basic molecular mechanisms
underlying tumor initiation, progression, metastasis, and therapy resistance,
which are the prerequisite for the development of novel treatment strategies and
clinical applications in cancer therapy.
PMID- 25136076
TI - Correlates and prognosis of early recurrence after catheter ablation for
ventricular tachycardia due to structural heart disease.
AB - BACKGROUND: Catheter ablation for ventricular tachycardia (VT) from structural
heart disease has a significant risk of recurrence, but the optimal duration for
in-hospital monitoring is not defined. This study assesses the timing,
correlates, and prognostic significance of early VT recurrence after ablation.
METHODS AND RESULTS: Of 370 patients (313 men; aged 63.0+/-13.2 years) who
underwent a first radiofrequency ablation for sustained monomorphic VT associated
with structural heart disease from 2008 to 2012, sustained VT recurred in 81
patients (22%) within 7 days. In multivariable analysis, early recurrence was
associated with New York Heart Association classification >=III (odds ratio [OR]
1.90, 95% confidence interval [CI] 1.03-3.48; P=0.04), dilated cardiomyopathy (OR
1.93, 95% CI 1.03-3.57; P=0.04), prevalence of VT storm before the procedure (OR
2.62, 95% CI 1.48-4.65; P=0.001), a greater number of induced VTs (OR 1.24, 95%
CI 1.07-1.45; P=0.006), and acute failure or no final induction test (OR 1.88,
95% CI 1.03-3.40; P=0.04). During a median of 2.5 (1.2, 4.0) years of follow-up,
early VT recurrence was an independent correlates of mortality (hazard ratio
2.59, 95% CI 1.52-4.34; P=0.0005). CONCLUSIONS: Patients who have early
recurrences of VT after ablation are a high risk group who may be identifiable
from their clinical profile. Further study is warranted to define the optimal
treatment strategies for this patient group.
PMID- 25136077
TI - Mortality reduction in relation to implantable cardioverter defibrillator
programming in the Multicenter Automatic Defibrillator Implantation Trial-Reduce
Inappropriate Therapy (MADIT-RIT).
AB - BACKGROUND: The benefit of novel implantable cardioverter defibrillator (ICD)
programming in reducing inappropriate ICD therapy and mortality was demonstrated
in Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate
Therapy (MADIT-RIT). However, the cause of mortality reduction remains
incompletely evaluated. We aimed to identify factors associated with mortality,
with focus on ICD therapy and programming in the MADIT-RIT population. METHODS
AND RESULTS: In MADIT-RIT, 1500 patients with a primary prophylactic indication
for ICD or cardiac resynchronization therapy with defibrillator were randomized
to 1 of 3 different ICD programming arms: conventional programming (ventricular
tachycardia zone >=170 beats per minute), high-rate programming (ventricular
tachycardia zone >=200 beats per minute), and delayed programming (60-second
delay before therapy >=170 beats per minute). Multivariate Cox models were used
to assess the influence of time-dependent appropriate and inappropriate ICD
therapy (shock and antitachycardia pacing) and randomized programming arm on all
cause mortality. During an average follow-up of 1.4+/-0.6 years, 71 of 1500 (5%)
patients died: cardiac in 40 patients (56.3%), noncardiac in 23 patients (32.4%),
and unknown in 8 patients (11.3%). Appropriate shocks (hazard ratio, 6.32; 95%
confidence interval, 3.13-12.75; P<0.001) and inappropriate therapy (hazard
ratio, 2.61; 95% confidence interval, 1.28-5.31; P=0.01) were significantly
associated with an increased mortality risk. There was no evidence of increased
mortality risk in patients who experienced appropriate antitachycardia pacing
only (hazard ratio, 1.02; 95% confidence interval, 0.36-2.88; P=0.98).
Randomization to conventional programming was identified as an independent
predictor of death when compared with patients randomized to high-rate
programming (hazard ratio, 2.0; 95% confidence interval, 1.06-3.71; P=0.03).
CONCLUSIONS: In MADIT-RIT, appropriate shocks, inappropriate ICD therapy, and
randomization to conventional ICD programming were independently associated with
an increased mortality risk. Appropriate antitachycardia pacing was not related
to an adverse outcome. CLINICAL TRIAL REGISTRATION URL: clinicaltrials.gov Unique
identifier: NCT00947310.
PMID- 25136081
TI - Therapeutic exercise for chronic non-specific neck pain: PEDro systematic review
update.
PMID- 25136078
TI - Detailed analysis of bone marrow from patients with ischemic heart disease and
left ventricular dysfunction: BM CD34, CD11b, and clonogenic capacity as
biomarkers for clinical outcomes.
AB - RATIONALE: Bone marrow (BM) cell therapy for ischemic heart disease (IHD) has
shown mixed results. Before the full potency of BM cell therapy can be realized,
it is essential to understand the BM niche after acute myocardial infarction
(AMI). OBJECTIVE: To study the BM composition in patients with IHD and severe
left ventricular (LV) dysfunction. METHODS AND RESULTS: BM from 280 patients with
IHD and LV dysfunction were analyzed for cell subsets by flow cytometry and
colony assays. BM CD34(+) cell percentage was decreased 7 days after AMI (mean of
1.9% versus 2.3%-2.7% in other cohorts; P<0.05). BM-derived endothelial colonies
were significantly decreased (P<0.05). Increased BM CD11b(+) cells associated
with worse LV ejection fraction (LVEF) after AMI (P<0.05). Increased BM CD34(+)
percentage associated with greater improvement in LVEF (+9.9% versus +2.3%;
P=0.03, for patients with AMI and +6.6% versus -0.02%; P=0.021 for patients with
chronic IHD). In addition, decreased BM CD34(+) percentage in patients with
chronic IHD correlated with decrement in LVEF (-2.9% versus +0.7%; P=0.0355).
CONCLUSIONS: In this study, we show a heterogeneous mixture of BM cell subsets,
decreased endothelial colony capacity, a CD34+ cell nadir 7 days after AMI, a
negative correlation between CD11b percentage and postinfarct LVEF, and positive
correlation of CD34 percentage with change in LVEF after cell therapy. These
results serve as a possible basis for the small clinical improvement seen in
autologous BM cell therapy trials and support selection of potent cell subsets
and reversal of comorbid BM impairment. CLINICAL TRIAL REGISTRATIONS URL:
http://www.clinicaltrials.gov. Unique identifiers: NCT00684021, NCT00684060, and
NCT00824005.
PMID- 25136080
TI - Incidence of periorbital necrotising fasciitis in the UK population: a BOSU
study.
AB - BACKGROUND: Periorbital necrotising fasciitis (PNF) is a devastating infection of
subcutaneous soft tissue and underlying fascia causing severe morbidity and even
loss of life. Few case reports of PNF exist and there are no prospective
epidemiological studies. METHODS: A prospective observational study was
undertaken using the British Ophthalmological Surveillance Unit reporting system.
Questionnaires were sent to reporting ophthalmologists in the UK seeking cases of
PNF over a 2-year period. RESULTS: 30 new cases were confirmed. 16 of the
reported cases followed a precipitating event, 9 cases followed trauma and 3
followed surgery. beta-haemolytic Streptococcus A was the causative organism
identified in 76%, either alone or with concurrent infection, and antibiotic
sensitivities are discussed. Systemic complications occurred in the majority of
cases (66.6%), with sepsis and death occurring in 10%. Over 50% of surviving
patients had subsequent morbidity, reduced acuity (<6/18) being common.
CONCLUSION: PNF is a rare, dangerous condition. This study identified an
incidence of 0.24 per 1,000,000 per annum in the UK. beta-haemolytic
Streptococcus A is the most common causative organism. Mortality remains a
potential outcome, and survivors suffer significant morbidity. Early intravenous
antibiotic management with a consensus favouring penicillin and clindamycin
combined with debridement.
PMID- 25136082
TI - Physiotherapy improves eating disorders and quality of life in bulimia and
anorexia nervosa.
PMID- 25136079
TI - Guidelines for the management of neovascular age-related macular degeneration by
the European Society of Retina Specialists (EURETINA).
AB - Age-related macular degeneration (AMD) is still referred to as the leading cause
of severe and irreversible visual loss world-wide. The disease has a profound
effect on quality of life of affected individuals and represents a major
socioeconomic challenge for societies due to the exponential increase in life
expectancy and environmental risks. Advances in medical research have identified
vascular endothelial growth factor (VEGF) as an important pathophysiological
player in neovascular AMD and intraocular inhibition of VEGF as one of the most
efficient therapies in medicine. The wide introduction of anti-VEGF therapy has
led to an overwhelming improvement in the prognosis of patients affected by
neovascular AMD, allowing recovery and maintenance of visual function in the vast
majority of patients. However, the therapeutic benefit is accompanied by
significant economic investments, unresolved medicolegal debates about the use of
off-label substances and overwhelming problems in large population management.
The burden of disease has turned into a burden of care with a dissociation of
scientific advances and real-world clinical performance. Simultaneously, ground
breaking innovations in diagnostic technologies, such as optical coherence
tomography, allows unprecedented high-resolution visualisation of disease
morphology and provides a promising horizon for early disease detection and
efficient therapeutic follow-up. However, definite conclusions from morphologic
parameters are still lacking, and valid biomarkers have yet to be identified to
provide a practical base for disease management. The European Society of Retina
Specialists offers expert guidance for diagnostic and therapeutic management of
neovascular AMD supporting healthcare givers and doctors in providing the best
state-of-the-art care to their patients. TRIAL REGISTRATION NUMBER: NCT01318941.
PMID- 25136084
TI - Effect of woody-plant encroachment on livestock production in North and South
America.
AB - A large fraction of the world grasslands and savannas are undergoing a rapid
shift from herbaceous to woody-plant dominance. This land-cover change is
expected to lead to a loss in livestock production (LP), but the impacts of woody
plant encroachment on this crucial ecosystem service have not been assessed. We
evaluate how tree cover (TC) has affected LP at large spatial scales in
rangelands of contrasting social-economic characteristics in the United States
and Argentina. Our models indicate that in areas of high productivity, a 1%
increase in TC results in a reduction in LP ranging from 0.6 to 1.6 reproductive
cows (Rc) per km(2). Mean LP in the United States is 27 Rc per km(2), so a 1%
increase in TC results in a 2.5% decrease in mean LP. This effect is large
considering that woody-plant cover has been described as increasing at 0.5% to 2%
per y. On the contrary, in areas of low productivity, increased TC had a positive
effect on LP. Our results also show that ecological factors account for a larger
fraction of LP variability in Argentinean than in US rangelands. Differences in
the relative importance of ecological versus nonecological drivers of LP in
Argentina and the United States suggest that the valuation of ecosystem services
between these two rangelands might be different. Current management strategies in
Argentina are likely designed to maximize LP for various reasons we are unable to
explore in this effort, whereas land managers in the United States may be
optimizing multiple ecosystem services, including conservation or recreation,
alongside LP.
PMID- 25136083
TI - TIM-family proteins inhibit HIV-1 release.
AB - Accumulating evidence indicates that T-cell immunoglobulin (Ig) and mucin domain
(TIM) proteins play critical roles in viral infections. Herein, we report that
the TIM-family proteins strongly inhibit HIV-1 release, resulting in diminished
viral production and replication. Expression of TIM-1 causes HIV-1 Gag and mature
viral particles to accumulate on the plasma membrane. Mutation of the
phosphatidylserine (PS) binding sites of TIM-1 abolishes its ability to block HIV
1 release. TIM-1, but to a much lesser extent PS-binding deficient mutants,
induces PS flipping onto the cell surface; TIM-1 is also found to be incorporated
into HIV-1 virions. Importantly, TIM-1 inhibits HIV-1 replication in CD4-positive
Jurkat cells, despite its capability of up-regulating CD4 and promoting HIV-1
entry. In addition to TIM-1, TIM-3 and TIM-4 also block the release of HIV-1, as
well as that of murine leukemia virus (MLV) and Ebola virus (EBOV); knockdown of
TIM-3 in differentiated monocyte-derived macrophages (MDMs) enhances HIV-1
production. The inhibitory effects of TIM-family proteins on virus release are
extended to other PS receptors, such as Axl and RAGE. Overall, our study uncovers
a novel ability of TIM-family proteins to block the release of HIV-1 and other
viruses by interaction with virion- and cell-associated PS. Our work provides new
insights into a virus-cell interaction that is mediated by TIMs and PS receptors.
PMID- 25136086
TI - Development of in-group favoritism in children's third-party punishment of
selfishness.
AB - When enforcing norms for cooperative behavior, human adults sometimes exhibit in
group bias. For example, third-party observers punish selfish behaviors committed
by out-group members more harshly than similar behaviors committed by in-group
members. Although evidence suggests that children begin to systematically punish
selfish behavior around the age of 6 y, the development of in-group bias in their
punishment remains unknown. Do children start off enforcing fairness norms
impartially, or is norm enforcement biased from its emergence? How does bias
change over development? Here, we created novel social groups in the laboratory
and gave 6- and 8-year-olds the opportunity to engage in costly third-party
punishment of selfish sharing behavior. We found that by age 6, punishment was
already biased: Selfish resource allocations received more punishment when they
were proposed by out-group members and when they disadvantaged in-group members.
We also found that although costly punishment increased between ages 6 and 8,
bias in punishment partially decreased. Although 8-y-olds also punished selfish
out-group members more harshly, they were equally likely to punish on behalf of
disadvantaged in-group and out-group members, perhaps reflecting efforts to
enforce norms impartially. Taken together, our results suggest that norm
enforcement is biased from its emergence, but that this bias can be partially
overcome through developmental change.
PMID- 25136085
TI - Narcolepsy patients have antibodies that stain distinct cell populations in rat
brain and influence sleep patterns.
AB - Narcolepsy is a chronic sleep disorder, likely with an autoimmune component.
During 2009 and 2010, a link between A(H1N1)pdm09 Pandemrix vaccination and onset
of narcolepsy was suggested in Scandinavia. In this study, we searched for
autoantibodies related to narcolepsy using a neuroanatomical array: rat brain
sections were processed for immunohistochemistry/double labeling using patient
sera/cerebrospinal fluid as primary antibodies. Sera from 89 narcoleptic
patients, 52 patients with other sleep-related disorders (OSRDs), and 137 healthy
controls were examined. Three distinct patterns of immunoreactivity were of
particular interest: pattern A, hypothalamic melanin-concentrating hormone and
proopiomelanocortin but not hypocretin/orexin neurons; pattern B, GABAergic
cortical interneurons; and pattern C, mainly globus pallidus neurons. Altogether,
24 of 89 (27%) narcoleptics exhibited pattern A or B or C. None of the patterns
were exclusive for narcolepsy but were also detected in the OSRD group at
significantly lower numbers. Also, some healthy controls exhibited these
patterns. The antigen of pattern A autoantibodies was identified as the common C
terminal epitope of neuropeptide glutamic acid-isoleucine/alpha-melanocyte
stimulating hormone (NEI/alphaMSH) peptides. Passive transfer experiments on rat
showed significant effects of pattern A human IgGs on rapid eye movement and slow
wave sleep time parameters in the inactive phase and EEG theta-power in the
active phase. We suggest that NEI/alphaMSH autoantibodies may interfere with the
fine regulation of sleep, contributing to the complex pathogenesis of narcolepsy
and OSRDs. Also, patterns B and C are potentially interesting, because recent
data suggest a relevance of those brain regions/neuron populations in the
regulation of sleep/arousal.
PMID- 25136087
TI - Fluvial network organization imprints on microbial co-occurrence networks.
AB - Recent studies highlight linkages among the architecture of ecological networks,
their persistence facing environmental disturbance, and the related patterns of
biodiversity. A hitherto unresolved question is whether the structure of the
landscape inhabited by organisms leaves an imprint on their ecological networks.
We analyzed, based on pyrosequencing profiling of the biofilm communities in 114
streams, how features inherent to fluvial networks affect the co-occurrence
networks that the microorganisms form in these biofilms. Our findings suggest
that hydrology and metacommunity dynamics, both changing predictably across
fluvial networks, affect the fragmentation of the microbial co-occurrence
networks throughout the fluvial network. The loss of taxa from co-occurrence
networks demonstrates that the removal of gatekeepers disproportionately
contributed to network fragmentation, which has potential implications for the
functions biofilms fulfill in stream ecosystems. Our findings are critical
because of increased anthropogenic pressures deteriorating stream ecosystem
integrity and biodiversity.
PMID- 25136089
TI - Vaccines against poverty.
AB - With the 2010s declared the Decade of Vaccines, and Millennium Development Goals
4 and 5 focused on reducing diseases that are potentially vaccine preventable,
now is an exciting time for vaccines against poverty, that is, vaccines against
diseases that disproportionately affect low- and middle-income countries (LMICs).
The Global Burden of Disease Study 2010 has helped better understand which
vaccines are most needed. In 2012, US$1.3 billion was spent on research and
development for new vaccines for neglected infectious diseases. However, the
majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and
not neglected diseases. Much of it went to basic research rather than
development, with an ongoing decline in funding for product development
partnerships. Further investment in vaccines against diarrheal diseases,
hepatitis C, and group A Streptococcus could lead to a major health impact in
LMICs, along with vaccines to prevent sepsis, particularly among mothers and
neonates. The Advanced Market Commitment strategy of the Global Alliance for
Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines
against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac
meningococcal A vaccine in the African Meningitis Belt represents a paradigm
shift in vaccines against poverty: the development of a vaccine primarily
targeted at LMICs. Global health vaccine institutes and increasing capacity of
vaccine manufacturers in emerging economies are helping drive forward new
vaccines for LMICs. Above all, partnership is needed between those developing and
manufacturing LMIC vaccines and the scientists, health care professionals, and
policy makers in LMICs where such vaccines will be implemented.
PMID- 25136088
TI - Introgression in hybrid ants is favored in females but selected against in males.
AB - Hybridization is not a mere reproductive dead end but has been suggested to play
a central role in speciation, for example, by introducing adaptive genetic
variation. Our previous study uncovered a unique consequence of hybridization in
Formica ants. In a population including two isolated but partially introgressed
genetic groups, the females have an apparent hybrid background, whereas the males
do not. This situation results in large-scale differences between male and female
genomes that are stable throughout generations. Here, we compare genotypes from
different developmental stages to investigate how sex-specific introgression and
genetic differences between sexes are maintained. We show that strong selection
rather than sex-dependent transmission maintains the genetic differences between
sexes. All genotype combinations are produced and observed in the eggs of both
sexes, but the alleles acquired through hybridization disappear from the haploid
males during development from egg to adult as their frequencies drop toward zero.
However, the same introgressed alleles increase in frequency and are favored when
heterozygous in the females. Genotypes eliminated from males most likely
represent incompatibilities arising from hybridization. Our results show an
unusual situation of opposite selection, where introgression is favored in
diploid females but selected against in haploid males. This finding suggests that
introgressed genomic regions harbor both fitness-enhancing and -reducing
elements. Our work highlights the complex consequences of hybridization and
provides a rare opportunity to observe natural selection in real time in nature.
PMID- 25136090
TI - Climate change poised to threaten hydrologic connectivity and endemic fishes in
dryland streams.
AB - Protecting hydrologic connectivity of freshwater ecosystems is fundamental to
ensuring species persistence, ecosystem integrity, and human well-being. More
frequent and severe droughts associated with climate change are poised to
significantly alter flow intermittence patterns and hydrologic connectivity in
dryland streams of the American Southwest, with deleterious effects on highly
endangered fishes. By integrating local-scale hydrologic modeling with emerging
approaches in landscape ecology, we quantify fine-resolution, watershed-scale
changes in habitat size, spacing, and connectance under forecasted climate change
in the Verde River Basin, United States. Model simulations project annual zero
flow day frequency to increase by 27% by midcentury, with differential seasonal
consequences on continuity (temporal continuity at discrete locations) and
connectivity (spatial continuity within the network). A 17% increase in the
frequency of stream drying events is expected throughout the network with
associated increases in the duration of these events. Flowing portions of the
river network will diminish between 8% and 20% in spring and early summer and
become increasingly isolated by more frequent and longer stretches of dry channel
fragments, thus limiting the opportunity for native fishes to access spawning
habitats and seasonally available refuges. Model predictions suggest that
midcentury and late century climate will reduce network-wide hydrologic
connectivity for native fishes by 6-9% over the course of a year and up to 12-18%
during spring spawning months. Our work quantifies climate-induced shifts in
stream drying and connectivity across a large river network and demonstrates
their implications for the persistence of a globally endemic fish fauna.
PMID- 25136091
TI - Reconstruction of scalar and vectorial components in X-ray dark-field tomography.
AB - Grating-based X-ray dark-field imaging is a novel technique for obtaining image
contrast for object structures at size scales below setup resolution. Such an
approach appears particularly beneficial for medical imaging and nondestructive
testing. It has already been shown that the dark-field signal depends on the
direction of observation. However, up to now, algorithms for fully recovering the
orientation dependence in a tomographic volume are still unexplored. In this
publication, we propose a reconstruction method for grating-based X-ray dark
field tomography, which models the orientation-dependent signal as an additional
observable from a standard tomographic scan. In detail, we extend the tomographic
volume to a tensorial set of voxel data, containing the local orientation and
contributions to dark-field scattering. In our experiments, we present the first
results of several test specimens exhibiting a heterogeneous composition in
microstructure, which demonstrates the diagnostic potential of the method.
PMID- 25136092
TI - Protein crystal structure obtained at 2.9 A resolution from injecting bacterial
cells into an X-ray free-electron laser beam.
AB - It has long been known that toxins produced by Bacillus thuringiensis (Bt) are
stored in the bacterial cells in crystalline form. Here we describe the structure
determination of the Cry3A toxin found naturally crystallized within Bt cells.
When whole Bt cells were streamed into an X-ray free-electron laser beam we found
that scattering from other cell components did not obscure diffraction from the
crystals. The resolution limits of the best diffraction images collected from
cells were the same as from isolated crystals. The integrity of the cells at the
moment of diffraction is unclear; however, given the short time (~ 5 us) between
exiting the injector to intersecting with the X-ray beam, our result is a 2.9-A
resolution structure of a crystalline protein as it exists in a living cell. The
study suggests that authentic in vivo diffraction studies can produce atomic
level structural information.
PMID- 25136093
TI - Adaptive growth factor delivery from a polyelectrolyte coating promotes
synergistic bone tissue repair and reconstruction.
AB - Traumatic wounds and congenital defects that require large-scale bone tissue
repair have few successful clinical therapies, particularly for
craniomaxillofacial defects. Although bioactive materials have demonstrated
alternative approaches to tissue repair, an optimized materials system for
reproducible, safe, and targeted repair remains elusive. We hypothesized that
controlled, rapid bone formation in large, critical-size defects could be induced
by simultaneously delivering multiple biological growth factors to the site of
the wound. Here, we report an approach for bone repair using a polyelectrolye
multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2
and platelet-derived growth factor-BB that were eluted over readily adapted time
scales to induce rapid bone repair. Based on electrostatic interactions between
the polymer multilayers and growth factors alone, we sustained mitogenic and
osteogenic signals with these growth factors in an easily tunable and controlled
manner to direct endogenous cell function. To prove the role of this adaptive
release system, we applied the polyelectrolyte coating on a well-studied
biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth
factors directed cellular processes to induce bone repair in a critical-size rat
calvaria model. The released growth factors promoted local bone formation that
bridged a critical-size defect in the calvaria as early as 2 wk after
implantation. Mature, mechanically competent bone regenerated the native calvaria
form. Such an approach could be clinically useful and has significant benefits as
a synthetic, off-the-shelf, cell-free option for bone tissue repair and
restoration.
PMID- 25136094
TI - Adaptive optoelectronic camouflage systems with designs inspired by cephalopod
skins.
AB - Octopus, squid, cuttlefish, and other cephalopods exhibit exceptional
capabilities for visually adapting to or differentiating from the coloration and
texture of their surroundings, for the purpose of concealment, communication,
predation, and reproduction. Long-standing interest in and emerging understanding
of the underlying ultrastructure, physiological control, and photonic
interactions has recently led to efforts in the construction of artificial
systems that have key attributes found in the skins of these organisms. Despite
several promising options in active materials for mimicking biological color
tuning, existing routes to integrated systems do not include critical
capabilities in distributed sensing and actuation. Research described here
represents progress in this direction, demonstrated through the construction,
experimental study, and computational modeling of materials, device elements, and
integration schemes for cephalopod-inspired flexible sheets that can autonomously
sense and adapt to the coloration of their surroundings. These systems combine
high-performance, multiplexed arrays of actuators and photodetectors in
laminated, multilayer configurations on flexible substrates, with overlaid
arrangements of pixelated, color-changing elements. The concepts provide
realistic routes to thin sheets that can be conformally wrapped onto solid
objects to modulate their visual appearance, with potential relevance to
consumer, industrial, and military applications.
PMID- 25136096
TI - Pseudomonas aeruginosa triggers CFTR-mediated airway surface liquid secretion in
swine trachea.
AB - Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by
mutations in the gene encoding for the anion channel cystic fibrosis
transmembrane conductance regulator (CFTR). Several organs are affected in CF,
but most of the morbidity and mortality comes from lung disease. Recent data show
that the initial consequence of CFTR mutation is the failure to eradicate
bacteria before the development of inflammation and airway remodeling. Bacterial
clearance depends on a layer of airway surface liquid (ASL) consisting of both a
mucus layer that traps, kills, and inactivates bacteria and a periciliary liquid
layer that keeps the mucus at an optimum distance from the underlying epithelia,
to maximize ciliary motility and clearance of bacteria. The airways in CF
patients and animal models of CF demonstrate abnormal ASL secretion and reduced
antimicrobial properties. Thus, it has been proposed that abnormal ASL secretion
in response to bacteria may facilitate the development of the infection and
inflammation that characterize CF airway disease. Whether the inhalation of
bacteria triggers ASL secretion, and the role of CFTR, have never been tested,
however. We developed a synchrotron-based imaging technique to visualize the ASL
layer and measure the effect of bacteria on ASL secretion. We show that the
introduction of Pseudomonas aeruginosa and other bacteria into the lumen of
intact isolated swine tracheas triggers CFTR-dependent ASL secretion by the
submucosal glands. This response requires expression of the bacterial protein
flagellin. In patients with CF, the inhalation of bacteria would fail to trigger
ASL secretion, leading to infection and inflammation.
PMID- 25136097
TI - Submesoscale dispersion in the vicinity of the Deepwater Horizon spill.
AB - Reliable forecasts for the dispersion of oceanic contamination are important for
coastal ecosystems, society, and the economy as evidenced by the Deepwater
Horizon oil spill in the Gulf of Mexico in 2010 and the Fukushima nuclear plant
incident in the Pacific Ocean in 2011. Accurate prediction of pollutant pathways
and concentrations at the ocean surface requires understanding ocean dynamics
over a broad range of spatial scales. Fundamental questions concerning the
structure of the velocity field at the submesoscales (100 m to tens of
kilometers, hours to days) remain unresolved due to a lack of synoptic
measurements at these scales. Using high-frequency position data provided by the
near-simultaneous release of hundreds of accurately tracked surface drifters, we
study the structure of submesoscale surface velocity fluctuations in the Northern
Gulf of Mexico. Observed two-point statistics confirm the accuracy of classic
turbulence scaling laws at 200-m to 50-km scales and clearly indicate that
dispersion at the submesoscales is local, driven predominantly by energetic
submesoscale fluctuations. The results demonstrate the feasibility and utility of
deploying large clusters of drifting instruments to provide synoptic observations
of spatial variability of the ocean surface velocity field. Our findings allow
quantification of the submesoscale-driven dispersion missing in current
operational circulation models and satellite altimeter-derived velocity fields.
PMID- 25136095
TI - Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease
in mice.
AB - Psoriasis (Ps) and psoriasis arthritis (PsA) are poorly understood common
diseases, induced by unknown environmental factors, affecting skin and articular
joints. A single i.p. exposure to mannan from Saccharomyces cerevisiae induced an
acute inflammation in inbred mouse strains resembling human Ps and PsA-like
disease, whereas multiple injections induced a relapsing disease. Exacerbation of
disease severity was observed in mice deficient for generation of reactive oxygen
species (ROS). Interestingly, restoration of ROS production, specifically in
macrophages, ameliorated both skin and joint disease. Neutralization of IL-17A,
mainly produced by gammadelta T cells, completely blocked disease symptoms.
Furthermore, mice depleted of granulocytes were resistant to disease development.
In contrast, certain acute inflammatory mediators (C5, Fcgamma receptor III, mast
cells, and histamine) and adaptive immune players (alphabeta T and B cells) were
redundant in disease induction. Hence, we propose that mannan-induced activation
of macrophages leads to TNF-alpha secretion and stimulation of local gammadelta T
cells secreting IL-17A. The combined action of activated macrophages and IL-17A
produced in situ drives neutrophil infiltration in the epidermis and dermis of
the skin, leading to disease manifestations. Thus, our finding suggests a new
mechanism triggered by exposure to exogenous microbial components, such as
mannan, that can induce and exacerbate Ps and PsA.
PMID- 25136098
TI - UV damage-induced RNA polymerase II stalling stimulates H2B deubiquitylation.
AB - Histone H2B monoubiquitylation plays an important role in RNA polymerase II
(RNAPII) elongation. Whether this modification responds to RNAPII stalling is not
yet known. We report that both yeast and human cells undergo a rapid and
significant H2B deubiquitylation after exposure to UV irradiation. This
deubiquitylation occurs concurrently with UV-induced transcription arrest and is
significantly reduced in a DNA damage-bypassing RNAPII yeast mutant. Consistent
with these results, yeast deubiquitylases Ubp8 and Ubp10 are associated with the
RNAPII complex. Moreover, simultaneous deletion of Ubp8 and Ubp10 leads to a lack
of H2B deubiquitylation after UV exposure. Consequently, nucleotide excision
repair at an actively transcribed gene locus is decreased, whereas UV-induced
RNAPII degradation is increased in ubp8Deltaubp10Delta mutant cells. These
results indicate that eukaryotic cells respond to RNAPII arrest by
deubiquitylating H2B to coordinate DNA repair and RNAPII degradation.
PMID- 25136099
TI - Gyrification from constrained cortical expansion.
AB - The exterior of the mammalian brain--the cerebral cortex--has a conserved layered
structure whose thickness varies little across species. However, selection
pressures over evolutionary time scales have led to cortices that have a large
surface area to volume ratio in some organisms, with the result that the brain is
strongly convoluted into sulci and gyri. Here we show that the gyrification can
arise as a nonlinear consequence of a simple mechanical instability driven by
tangential expansion of the gray matter constrained by the white matter. A
physical mimic of the process using a layered swelling gel captures the essence
of the mechanism, and numerical simulations of the brain treated as a soft solid
lead to the formation of cusped sulci and smooth gyri similar to those in the
brain. The resulting gyrification patterns are a function of relative cortical
expansion and relative thickness (compared with brain size), and are consistent
with observations of a wide range of brains, ranging from smooth to highly
convoluted. Furthermore, this dependence on two simple geometric parameters that
characterize the brain also allows us to qualitatively explain how variations in
these parameters lead to anatomical anomalies in such situations as
polymicrogyria, pachygyria, and lissencephalia.
PMID- 25136100
TI - Label-free probe of HIV-1 TAT peptide binding to mimetic membranes.
AB - The transacting activator of transduction (TAT) protein plays a key role in the
progression of AIDS. Studies have shown that a +8 charged sequence of amino acids
in the protein, called the TAT peptide, enables the TAT protein to penetrate cell
membranes. To probe mechanisms of binding and translocation of the TAT peptide
into the cell, investigators have used phospholipid liposomes as cell membrane
mimics. We have used the method of surface potential sensitive second harmonic
generation (SHG), which is a label-free and interface-selective method, to study
the binding of TAT to anionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-1'-rac
glycerol (POPG) and neutral 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine
(POPC) liposomes. It is the SHG sensitivity to the electrostatic field generated
by a charged interface that enabled us to obtain the interfacial electrostatic
potential. SHG together with the Poisson-Boltzmann equation yielded the
dependence of the surface potential on the density of adsorbed TAT. We obtained
the dissociation constants Kd for TAT binding to POPC and POPG liposomes and the
maximum number of TATs that can bind to a given liposome surface. For POPC Kd was
found to be 7.5 +/- 2 MUM, and for POPG Kd was 29.0 +/- 4.0 MUM. As TAT was added
to the liposome solution the POPC surface potential changed from 0 mV to +37 mV,
and for POPG it changed from -57 mV to -37 mV. A numerical calculation of Kd,
which included all terms obtained from application of the Poisson-Boltzmann
equation to the TAT liposome SHG data, was shown to be in good agreement with an
approximated solution.
PMID- 25136101
TI - Adaptive, convergent origins of the pygmy phenotype in African rainforest hunter
gatherers.
AB - The evolutionary history of the human pygmy phenotype (small body size), a
characteristic of African and Southeast Asian rainforest hunter-gatherers, is
largely unknown. Here we use a genome-wide admixture mapping analysis to identify
16 genomic regions that are significantly associated with the pygmy phenotype in
the Batwa, a rainforest hunter-gatherer population from Uganda (east central
Africa). The identified genomic regions have multiple attributes that provide
supporting evidence of genuine association with the pygmy phenotype, including
enrichments for SNPs previously associated with stature variation in Europeans
and for genes with growth hormone receptor and regulation functions. To test
adaptive evolutionary hypotheses, we computed the haplotype-based integrated
haplotype score (iHS) statistic and the level of population differentiation (FST)
between the Batwa and their agricultural neighbors, the Bakiga, for each genomic
SNP. Both |iHS| and FST values were significantly higher for SNPs within the
Batwa pygmy phenotype-associated regions than the remainder of the genome, a
signature of polygenic adaptation. In contrast, when we expanded our analysis to
include Baka rainforest hunter-gatherers from Cameroon and Gabon (west central
Africa) and Nzebi and Nzime neighboring agriculturalists, we did not observe
elevated |iHS| or FST values in these genomic regions. Together, these results
suggest adaptive and at least partially convergent origins of the pygmy phenotype
even within Africa, supporting the hypothesis that small body size confers a
selective advantage for tropical rainforest hunter-gatherers but raising
questions about the antiquity of this behavior.
PMID- 25136102
TI - Systems vaccinology: probing humanity's diverse immune systems with vaccines.
AB - Homo sapiens are genetically diverse, but dramatic demographic and socioeconomic
changes during the past century have created further diversification with respect
to age, nutritional status, and the incidence of associated chronic inflammatory
disorders and chronic infections. These shifting demographics pose new challenges
for vaccination, as emerging evidence suggests that age, the metabolic state, and
chronic infections can exert major influences on the immune system. Thus, a key
public health challenge is learning how to reprogram suboptimal immune systems to
induce effective vaccine immunity. Recent advances have applied systems
biological analysis to define molecular signatures induced early after
vaccination that correlate with and predict the later adaptive immune responses
in humans. Such "systems vaccinology" approaches offer an integrated picture of
the molecular networks driving vaccine immunity, and are beginning to yield novel
insights about the immune system. Here we discuss the promise of systems
vaccinology in probing humanity's diverse immune systems, and in delineating the
impact of genes, the environment, and the microbiome on protective immunity
induced by vaccination. Such insights will be critical in reengineering
suboptimal immune systems in immunocompromised populations.
PMID- 25136103
TI - Genetic and pharmacological reactivation of the mammalian inactive X chromosome.
AB - X-chromosome inactivation (XCI), the random transcriptional silencing of one X
chromosome in somatic cells of female mammals, is a mechanism that ensures equal
expression of X-linked genes in both sexes. XCI is initiated in cis by the
noncoding Xist RNA, which coats the inactive X chromosome (Xi) from which it is
produced. However, trans-acting factors that mediate XCI remain largely unknown.
Here, we perform a large-scale RNA interference screen to identify trans-acting
XCI factors (XCIFs) that comprise regulators of cell signaling and transcription,
including the DNA methyltransferase, DNMT1. The expression pattern of the XCIFs
explains the selective onset of XCI following differentiation. The XCIFs
function, at least in part, by promoting expression and/or localization of Xist
to the Xi. Surprisingly, we find that DNMT1, which is generally a transcriptional
repressor, is an activator of Xist transcription. Small-molecule inhibitors of
two of the XCIFs can reversibly reactivate the Xi, which has implications for
treatment of Rett syndrome and other dominant X-linked diseases. A homozygous
mouse knockout of one of the XCIFs, stanniocalcin 1 (STC1), has an expected XCI
defect but surprisingly is phenotypically normal. Remarkably, X-linked genes are
not overexpressed in female Stc1(-/-) mice, revealing the existence of a
mechanism(s) that can compensate for a persistent XCI deficiency to regulate X
linked gene expression.
PMID- 25136106
TI - QnAs with Patricia Kuhl.
PMID- 25136104
TI - Direct measurement of the dielectric polarization properties of DNA.
AB - The electric polarizability of DNA, represented by the dielectric constant, is a
key intrinsic property that modulates DNA interaction with effector proteins.
Surprisingly, it has so far remained unknown owing to the lack of experimental
tools able to access it. Here, we experimentally resolved it by detecting the
ultraweak polarization forces of DNA inside single T7 bacteriophages particles
using electrostatic force microscopy. In contrast to the common assumption of low
polarizable behavior like proteins (epsilonr ~ 2-4), we found that the DNA
dielectric constant is ~ 8, considerably higher than the value of ~ 3 found for
capsid proteins. State-of-the-art molecular dynamic simulations confirm the
experimental findings, which result in sensibly decreased DNA interaction free
energy than normally predicted by Poisson-Boltzmann methods. Our findings reveal
a property at the basis of DNA structure and functions that is needed for
realistic theoretical descriptions, and illustrate the synergetic power of
scanning probe microscopy and theoretical computation techniques.
PMID- 25136105
TI - Robustness against serum neutralization of a poliovirus type 1 from a lethal
epidemic of poliomyelitis in the Republic of Congo in 2010.
AB - In 2010, a large outbreak of poliomyelitis with unusual 47% lethality occurred in
Pointe Noire, Republic of Congo. Vaccine-mediated immunity against the outbreak
virus was never investigated. A wild poliovirus 1 (WPV1) isolated from a fatal
case (termed PV1-RC2010) showed a previously unknown combination of amino acid
exchanges in critical antigenic site 2 (AgS2, VP1 capsid protein positions
221SAAL -> 221PADL). These exchanges were also detected in an additional 11 WPV1
strains from fatal cases. PV1-RC2010 escaped neutralization by three different
mAbs relevant for AgS2. Virus neutralization was tested in sera from fatal cases,
who died before supplementary immunization (n = 24), Gabonese recipients of
recent oral polio vaccination (n = 12), routinely vaccinated German medical
students (n = 34), and German outpatients tested for antipoliovirus immunity (n =
17) on Vero, human rhabdomyosarcoma, and human epidermoid carcinoma 2 cells.
Fatal poliomyelitis cases gave laboratory evidence of previous trivalent
vaccination. Neutralizing antibody titers against PV1-RC2010 were significantly
lower than those against the vaccine strain Sabin-1, two genetically distinct
WPV1s isolated in 1965 and 2010 and two genetically distinct vaccine-derived PV
strains. Of German vaccinees tested according to World Health Organization
protocols, 15-29% were unprotected according to their neutralization titers (<1:8
serum dilution), even though all were protected against Sabin-1. Phylogenetic
analysis of the WPV1 outbreak strains suggested a recent introduction of virus
progenitors from Asia with formation of separate Angolan and Congolese lineages.
Only the latter carried both critical AgS2 mutations. Antigenetically variant PVs
may become relevant during the final phase of poliomyelitis eradication in
populations with predominantly vaccine-derived immunity. Sustained vaccination
coverage and clinical and environmental surveillance will be necessary.
PMID- 25136107
TI - Illegal killing for ivory drives global decline in African elephants.
AB - Illegal wildlife trade has reached alarming levels globally, extirpating
populations of commercially valuable species. As a driver of biodiversity loss,
quantifying illegal harvest is essential for conservation and sociopolitical
affairs but notoriously difficult. Here we combine field-based carcass monitoring
with fine-scale demographic data from an intensively studied wild African
elephant population in Samburu, Kenya, to partition mortality into natural and
illegal causes. We then expand our analytical framework to model illegal killing
rates and population trends of elephants at regional and continental scales using
carcass data collected by a Convention on International Trade in Endangered
Species program. At the intensively monitored site, illegal killing increased
markedly after 2008 and was correlated strongly with the local black market ivory
price and increased seizures of ivory destined for China. More broadly, results
from application to continental data indicated illegal killing levels were
unsustainable for the species between 2010 and 2012, peaking to ~ 8% in 2011
which extrapolates to ~ 40,000 elephants illegally killed and a probable species
reduction of ~ 3% that year. Preliminary data from 2013 indicate overharvesting
continued. In contrast to the rest of Africa, our analysis corroborates that
Central African forest elephants experienced decline throughout the last decade.
These results provide the most comprehensive assessment of illegal ivory harvest
to date and confirm that current ivory consumption is not sustainable. Further,
our approach provides a powerful basis to determine cryptic mortality and gain
understanding of the demography of at-risk species.
PMID- 25136108
TI - Trachyandesitic volcanism in the early Solar System.
AB - Volcanism is a substantial process during crustal growth on planetary bodies and
well documented to have occurred in the early Solar System from the recognition
of numerous basaltic meteorites. Considering the ureilite parent body (UPB), the
compositions of magmas that formed a potential UPB crust and were complementary
to the ultramafic ureilite mantle rocks are poorly constrained. Among the
Almahata Sitta meteorites, a unique trachyandesite lava (with an oxygen isotope
composition identical to that of common ureilites) documents the presence of
volatile- and SiO2-rich magmas on the UPB. The magma was extracted at low degrees
of disequilibrium partial melting of the UPB mantle. This trachyandesite extends
the range of known ancient volcanic, crust-forming rocks and documents that
volcanic rocks, similar in composition to trachyandesites on Earth, also formed
on small planetary bodies ~ 4.56 billion years ago. It also extends the volcanic
activity on the UPB by ~ 1 million years (Ma) and thus constrains the time of
disruption of the body to later than 6.5 Ma after the formation of Ca-Al-rich
inclusions.
PMID- 25136109
TI - Optogenetic neuronal stimulation promotes functional recovery after stroke.
AB - Clinical and research efforts have focused on promoting functional recovery after
stroke. Brain stimulation strategies are particularly promising because they
allow direct manipulation of the target area's excitability. However, elucidating
the cell type and mechanisms mediating recovery has been difficult because
existing stimulation techniques nonspecifically target all cell types near the
stimulated site. To circumvent these barriers, we used optogenetics to
selectively activate neurons that express channelrhodopsin 2 and demonstrated
that selective neuronal stimulations in the ipsilesional primary motor cortex
(iM1) can promote functional recovery. Stroke mice that received repeated
neuronal stimulations exhibited significant improvement in cerebral blood flow
and the neurovascular coupling response, as well as increased expression of
activity-dependent neurotrophins in the contralesional cortex, including brain
derived neurotrophic factor, nerve growth factor, and neurotrophin 3. Western
analysis also indicated that stimulated mice exhibited a significant increase in
the expression of a plasticity marker growth-associated protein 43. Moreover, iM1
neuronal stimulations promoted functional recovery, as stimulated stroke mice
showed faster weight gain and performed significantly better in sensory-motor
behavior tests. Interestingly, stimulations in normal nonstroke mice did not
alter motor behavior or neurotrophin expression, suggesting that the prorecovery
effect of selective neuronal stimulations is dependent on the poststroke
environment. These results demonstrate that stimulation of neurons in the stroke
hemisphere is sufficient to promote recovery.
PMID- 25136111
TI - Does aquaculture add resilience to the global food system?
AB - Aquaculture is the fastest growing food sector and continues to expand alongside
terrestrial crop and livestock production. Using portfolio theory as a conceptual
framework, we explore how current interconnections between the aquaculture, crop,
livestock, and fisheries sectors act as an impediment to, or an opportunity for,
enhanced resilience in the global food system given increased resource scarcity
and climate change. Aquaculture can potentially enhance resilience through
improved resource use efficiencies and increased diversification of farmed
species, locales of production, and feeding strategies. However, aquaculture's
reliance on terrestrial crops and wild fish for feeds, its dependence on
freshwater and land for culture sites, and its broad array of environmental
impacts diminishes its ability to add resilience. Feeds for livestock and farmed
fish that are fed rely largely on the same crops, although the fraction destined
for aquaculture is presently small (~4%). As demand for high-value fed
aquaculture products grows, competition for these crops will also rise, as will
the demand for wild fish as feed inputs. Many of these crops and forage fish are
also consumed directly by humans and provide essential nutrition for low-income
households. Their rising use in aquafeeds has the potential to increase price
levels and volatility, worsening food insecurity among the most vulnerable
populations. Although the diversification of global food production systems that
includes aquaculture offers promise for enhanced resilience, such promise will
not be realized if government policies fail to provide adequate incentives for
resource efficiency, equity, and environmental protection.
PMID- 25136110
TI - Formation and structures of GroEL:GroES2 chaperonin footballs, the protein
folding functional form.
AB - The GroE chaperonins assist substrate protein (SP) folding by cycling through
several conformational states. With each cycle the SP is, in turn, captured,
unfolded, briefly encapsulated (t1/2 ~ 1 s), and released by the chaperonin
complex. The protein-folding functional form is the US-football-shaped
GroEL:GroES2 complex. We report structures of two such "football" complexes to ~
3.7-A resolution; one is empty whereas the other contains encapsulated SP in both
chambers. Although encapsulated SP is not visible on the electron density map,
using calibrated FRET and order-of-addition experiments we show that owing to SP
catalyzed ADP/ATP exchange both chambers of the football complex encapsulate SP
efficiently only if the binding of SP precedes that of ATP. The two rings of
GroEL thus behave as a parallel processing machine, rather than functioning
alternately. Compared with the bullet-shaped GroEL:GroES1 complex, the
GroEL:GroES2 football complex differs conformationally at the GroEL-GroES
interface and also at the interface between the two GroEL rings. We propose that
the electrostatic interactions between the epsilon-NH(3+) of K105 of helix D in
one ring with the negatively charged carboxyl oxygen of A109 at the carboxyl end
of helix D of the other ring provide the structural basis for negative inter-ring
cooperativity.
PMID- 25136112
TI - Automodification switches PARP-1 function from chromatin architectural protein to
histone chaperone.
AB - Poly [ADP-ribose] polymerase 1 (PARP-1) is a highly abundant chromatin-associated
enzyme. It catalyzes the NAD(+)-dependent polymerization of long chains of poly
ADP ribose (PAR) onto itself in response to DNA damage and other cues. More
recently, the enzymatic activity of PARP-1 has also been implicated in the
regulation of gene expression. The molecular basis for the functional switch from
chromatin architectural protein to transcription factor and DNA damage responder,
triggered by PARP-1 automodification, is unknown. Here, we show that unmodified
PARP-1 engages in at least two high-affinity binding modes with chromatin, one of
which does not involve free DNA ends, consistent with its role as a chromatin
architectural protein. Automodification reduces PARP-1 affinity for intact
chromatin but not for nucleosomes with exposed DNA ends. Automodified (AM) PARP-1
has the ability to sequester histones (both in vitro and in cells) and to
assemble nucleosomes efficiently in vitro. This unanticipated nucleosome assembly
activity of AM-PARP-1, coupled with the fast turnover of the modification,
suggests a model in which DNA damage or transcription events trigger transient
histone chaperone activity.
PMID- 25136113
TI - IL-6/STAT3 promotes regeneration of airway ciliated cells from basal stem cells.
AB - The pseudostratified airway epithelium of the lung contains a balanced proportion
of multiciliated and secretory luminal cells that are maintained and regenerated
by a population of basal stem cells. However, little is known about how these
processes are modulated in vivo, and about the potential role of cytokine
signaling between stem and progenitor cells and their niche. Using a clonal 3D
organoid assay, we found that IL-6 stimulated, and Stat3 inhibitors reduced, the
generation of ciliated vs. secretory cells from basal cells. Gain-of-function and
loss-of-function studies with cultured mouse and human basal cells suggest that
IL-6/Stat3 signaling promotes ciliogenesis at multiple levels, including
increases in multicilin gene and forkhead box protein J1 expression and
inhibition of the Notch pathway. To test the role of IL-6 in vivo genetically, we
followed the regeneration of mouse tracheal epithelium after ablation of luminal
cells by inhaled SO2. Stat3 is activated in basal cells and their daughters early
in the repair process, correlating with an increase in Il-6 expression in
platelet-derived growth factor receptor alpha(+) mesenchymal cells in the stroma.
Conditional deletion in basal cells of suppressor of cytokine signaling 3,
encoding a negative regulator of the Stat3 pathway, results in an increase in
multiciliated cells at the expense of secretory and basal cells. By contrast, Il
6 null mice regenerate fewer ciliated cells and an increased number of secretory
cells after injury. The results support a model in which IL-6, produced in the
reparative niche, functions to enhance the differentiation of basal cells, and
thereby acts as a "friend" to promote airway repair rather than a "foe."
PMID- 25136114
TI - Molecular mechanism of pH-dependent substrate transport by an arginine-agmatine
antiporter.
AB - Enteropathogenic bacteria, exemplified by Escherichia coli, rely on acid
resistance systems (ARs) to survive the acidic environment of the stomach. AR3
consumes intracellular protons through decarboxylation of arginine (Arg) in the
cytoplasm and exchange of the reaction product agmatine (Agm) with extracellular
Arg. The latter process is mediated by the Arg:Agm antiporter AdiC, which is
activated in response to acidic pH and remains fully active at pH 6.0 and below.
Despite our knowledge of structural information, the molecular mechanism by which
AdiC senses acidic pH remains completely unknown. Relying on alanine-scanning
mutagenesis and an in vitro proteoliposome-based transport assay, we have
identified Tyr74 as a critical pH sensor in AdiC. The AdiC variant Y74A exhibited
robust transport activity at all pH values examined while maintaining stringent
substrate specificity for Arg:Agm. Replacement of Tyr74 by Phe, but not by any
other amino acid, led to the maintenance of pH-dependent substrate transport.
These observations, in conjunction with structural information, identify a
working model for pH-induced activation of AdiC in which a closed conformation is
disrupted by cation-pi interactions between proton and the aromatic side chain of
Tyr74.
PMID- 25136116
TI - Crystal structure of a nematode-infecting virus.
AB - Orsay, the first virus discovered to naturally infect Caenorhabditis elegans or
any nematode, has a bipartite, positive-sense RNA genome. Sequence analyses show
that Orsay is related to nodaviruses, but molecular characterizations of Orsay
reveal several unique features, such as the expression of a capsid-delta fusion
protein and the use of an ATG-independent mechanism for translation initiation.
Here we report the crystal structure of an Orsay virus-like particle assembled
from recombinant capsid protein (CP). Orsay capsid has a T = 3 icosahedral
symmetry with 60 trimeric surface spikes. Each CP can be divided into three
regions: an N-terminal arm that forms an extended protein interaction network at
the capsid interior, an S domain with a jelly-roll, beta-barrel fold forming the
continuous capsid, and a P domain that forms surface spike projections. The
structure of the Orsay S domain is best aligned to T = 3 plant RNA viruses but
exhibits substantial differences compared with the insect-infecting
alphanodaviruses, which also lack the P domain in their CPs. The Orsay P domain
is remotely related to the P1 domain in calicivirus and hepatitis E virus,
suggesting a possible evolutionary relationship. Removing the N-terminal arm
produced a slightly expanded capsid with fewer nucleic acids packaged, suggesting
that the arm is important for capsid stability and genome packaging. Because C.
elegans-Orsay serves as a highly tractable model for studying viral pathogenesis,
our results should provide a valuable structural framework for further studies of
Orsay replication and infection.
PMID- 25136115
TI - Mutation of Plekha7 attenuates salt-sensitive hypertension in the rat.
AB - PLEKHA7 (pleckstrin homology domain containing family A member 7) has been found
in multiple studies as a candidate gene for human hypertension, yet functional
data supporting this association are lacking. We investigated the contribution of
this gene to the pathogenesis of salt-sensitive hypertension by mutating Plekha7
in the Dahl salt-sensitive (SS/JrHsdMcwi) rat using zinc-finger nuclease
technology. After four weeks on an 8% NaCl diet, homozygous mutant rats had lower
mean arterial (149 +/- 9 mmHg vs. 178 +/- 7 mmHg; P < 0.05) and systolic (180 +/-
7 mmHg vs. 213 +/- 8 mmHg; P < 0.05) blood pressure compared with WT littermates.
Albumin and protein excretion rates were also significantly lower in mutant rats,
demonstrating a renoprotective effect of the mutation. Total peripheral
resistance and perivascular fibrosis in the heart and kidney were significantly
reduced in Plekha7 mutant animals, suggesting a potential role of the vasculature
in the attenuation of hypertension. Indeed, both flow-mediated dilation and
endothelium-dependent vasodilation in response to acetylcholine were improved in
isolated mesenteric resistance arteries of Plekha7 mutant rats compared with WT.
These vascular improvements were correlated with changes in intracellular calcium
handling, resulting in increased nitric oxide bioavailability in mutant vessels.
Collectively, these data provide the first functional evidence that Plekha7 may
contribute to blood pressure regulation and cardiovascular function through its
effects on the vasculature.
PMID- 25136118
TI - Tomato yellow leaf curl virus resistance by Ty-1 involves increased cytosine
methylation of viral genomes and is compromised by cucumber mosaic virus
infection.
AB - Tomato yellow leaf curl virus (TYLCV) and related begomoviruses are a major
threat to tomato production worldwide and, to protect against these viruses,
resistance genes from different wild tomato species are introgressed. Recently,
the Ty-1 resistance gene was identified, shown to code for an RNA-dependent RNA
polymerase and to be allelic with Ty-3. Here we show that upon TYLCV challenging
of resistant lines carrying Ty-1 or Ty-3, low virus titers were detected
concomitant with the production of relatively high levels of siRNAs whereas, in
contrast, susceptible tomato Moneymaker (MM) revealed higher virus titers but
lower amounts of siRNAs. Comparative analysis of the spatial genomic siRNA
distribution showed a consistent and subtle enrichment for siRNAs derived from
the V1 and C3 genes in Ty-1 and Ty-3. In plants containing Ty-2 resistance the
virus was hardly detectable, but the siRNA profile resembled the one observed in
TYLCV-challenged susceptible tomato (MM). Furthermore, a relative
hypermethylation of the TYLCV V1 promoter region was observed in genomic DNA
collected from Ty-1 compared with that from (MM). The resistance conferred by Ty
1 was also effective against the bipartite tomato severe rugose begomovirus,
where a similar genome hypermethylation of the V1 promoter region was discerned.
However, a mixed infection of TYLCV with cucumber mosaic virus compromised the
resistance. The results indicate that Ty-1 confers resistance to geminiviruses by
increasing cytosine methylation of viral genomes, suggestive of enhanced
transcriptional gene silencing. The mechanism of resistance and its durability
toward geminiviruses under natural field conditions is discussed.
PMID- 25136117
TI - Trithorax complex component Menin controls differentiation and maintenance of T
helper 17 cells.
AB - Epigenetic modifications, such as posttranslational modifications of histones,
play an important role in gene expression and regulation. These modifications are
in part mediated by the Trithorax group (TrxG) complex and the Polycomb group
(PcG) complex, which activate and repress transcription, respectively. We herein
investigate the role of Menin, a component of the TrxG complex in T helper (Th)
cell differentiation and show a critical role for Menin in differentiation and
maintenance of Th17 cells. Menin(-/-) T cells do not efficiently differentiate
into Th17 cells, leaving Th1 and Th2 cell differentiation intact in in vitro
cultures. Menin deficiency resulted in the attenuation of Th17-induced airway
inflammation. In differentiating Th17 cells, Menin directly bound to the Il17a
gene locus and was required for the deposition of permissive histone
modifications and recruitment of the RNA polymerase II transcriptional complex.
Interestingly, although Menin bound to the Rorc locus, Menin was dispensable for
the induction of Rorc expression and permissive histone modifications in
differentiating Th17 cells. In contrast, Menin was required to maintain
expression of Rorc in differentiated Th17 cells, indicating that Menin is
essential to stabilize expression of the Rorc gene. Thus, Menin orchestrates Th17
cell differentiation and function by regulating both the induction and
maintenance of target gene expression.
PMID- 25136119
TI - Electrostatics-driven shape transitions in soft shells.
AB - Manipulating the shape of nanoscale objects in a controllable fashion is at the
heart of designing materials that act as building blocks for self-assembly or
serve as targeted drug delivery carriers. Inducing shape deformations by
controlling external parameters is also an important way of designing biomimetic
membranes. In this paper, we demonstrate that electrostatics can be used as a
tool to manipulate the shape of soft, closed membranes by tuning environmental
conditions such as the electrolyte concentration in the medium. Using a molecular
dynamics-based simulated annealing procedure, we investigate charged elastic
shells that do not exchange material with their environment, such as elastic
membranes formed in emulsions or synthetic nanocontainers. We find that by
decreasing the salt concentration or increasing the total charge on the shell's
surface, the spherical symmetry is broken, leading to the formation of
ellipsoids, discs, and bowls. Shape changes are accompanied by a significant
lowering of the electrostatic energy and a rise in the surface area of the shell.
To substantiate our simulation findings, we show analytically that a uniformly
charged disc has a lower Coulomb energy than a sphere of the same volume.
Further, we test the robustness of our results by including the effects of charge
renormalization in the analysis of the shape transitions and find the latter to
be feasible for a wide range of shell volume fractions.
PMID- 25136120
TI - Activated group 3 innate lymphoid cells promote T-cell-mediated immune responses.
AB - Group 3 innate lymphoid cells (ILC3s) have emerged as important cellular players
in tissue repair and innate immunity. Whether these cells meaningfully regulate
adaptive immune responses upon activation has yet to be explored. Here we show
that upon IL-1beta stimulation, peripheral ILC3s become activated, secrete
cytokines, up-regulate surface MHC class II molecules, and express costimulatory
molecules. ILC3s can take up latex beads, process protein antigen, and
consequently prime CD4(+) T-cell responses in vitro. The cognate interaction of
ILC3s and CD4(+) T cells leads to T-cell proliferation both in vitro and in vivo,
whereas its disruption impairs specific T-cell and T-dependent B-cell responses
in vivo. In addition, the ILC3-CD4(+) T-cell interaction is bidirectional and
leads to the activation of ILC3s. Taken together, our data reveal a novel
activation-dependent function of peripheral ILC3s in eliciting cognate CD4(+) T
cell immune responses.
PMID- 25136121
TI - Immune evasion mediated by tumor-derived lactate dehydrogenase induction of NKG2D
ligands on myeloid cells in glioblastoma patients.
AB - Myeloid cells are key regulators of the tumor microenvironment, governing local
immune responses. Here we report that tumor-infiltrating myeloid cells and
circulating monocytes in patients with glioblastoma multiforme (GBM) express
ligands for activating the Natural killer group 2, member D (NKG2D) receptor,
which cause down-regulation of NKG2D on natural killer (NK) cells. Tumor
infiltrating NK cells isolated from GBM patients fail to lyse NKG2D ligand
expressing tumor cells. We demonstrate that lactate dehydrogenase (LDH) isoform 5
secreted by glioblastoma cells induces NKG2D ligands on monocytes isolated from
healthy individuals. Furthermore, sera from GBM patients contain elevated amounts
of LDH, which correlate with expression of NKG2D ligands on their autologous
circulating monocytes. NKG2D ligands also are present on circulating monocytes
isolated from patients with breast, prostate, and hepatitis C virus-induced
hepatocellular carcinomas. Together, these findings reveal a previously
unidentified immune evasion strategy whereby tumors produce soluble factors that
induce NKG2D ligands on myeloid cells, subverting antitumor immune responses.
PMID- 25136122
TI - Stimulation of growth by proteorhodopsin phototrophy involves regulation of
central metabolic pathways in marine planktonic bacteria.
AB - Proteorhodopsin (PR) is present in half of surface ocean bacterioplankton, where
its light-driven proton pumping provides energy to cells. Indeed, PR promotes
growth or survival in different bacteria. However, the metabolic pathways
mediating the light responses remain unknown. We analyzed growth of the PR
containing Dokdonia sp. MED134 (where light-stimulated growth had been found) in
seawater with low concentrations of mixed [yeast extract and peptone (YEP)] or
single (alanine, Ala) carbon compounds as models for rich and poor environments.
We discovered changes in gene expression revealing a tightly regulated shift in
central metabolic pathways between light and dark conditions. Bacteria showed
relatively stronger light responses in Ala compared with YEP. Notably, carbon
acquisition pathways shifted toward anaplerotic CO2 fixation in the light,
contributing 31 +/- 8% and 24 +/- 6% of the carbon incorporated into biomass in
Ala and YEP, respectively. Thus, MED134 was a facultative double mixotroph, i.e.,
photo- and chemotrophic for its energy source and using both bicarbonate and
organic matter as carbon sources. Unexpectedly, relative expression of the
glyoxylate shunt genes (isocitrate lyase and malate synthase) was >300-fold
higher in the light--but only in Ala--contributing a more efficient use of carbon
from organic compounds. We explored these findings in metagenomes and
metatranscriptomes and observed similar prevalence of the glyoxylate shunt
compared with PR genes and highest expression of the isocitrate lyase gene
coinciding with highest solar irradiance. Thus, regulatory interactions between
dissolved organic carbon quality and central metabolic pathways critically
determine the fitness of surface ocean bacteria engaging in PR phototrophy.
PMID- 25136123
TI - Mitochondrial reactive oxygen species are scavenged by Cockayne syndrome B
protein in human fibroblasts without nuclear DNA damage.
AB - Cockayne syndrome (CS) is a human DNA repair-deficient disease that involves
transcription coupled repair (TCR), in which three gene products, Cockayne
syndrome A (CSA), Cockayne syndrome B (CSB), and ultraviolet stimulated scaffold
protein A (UVSSA) cooperate in relieving RNA polymerase II arrest at damaged
sites to permit repair of the template strand. Mutation of any of these three
genes results in cells with increased sensitivity to UV light and defective TCR.
Mutations in CSA or CSB are associated with severe neurological disease but
mutations in UVSSA are for the most part only associated with increased
photosensitivity. This difference raises questions about the relevance of TCR to
neurological disease in CS. We find that CSB-mutated cells, but not UVSSA
deficient cells, have increased levels of intramitochondrial reactive oxygen
species (ROS), especially when mitochondrial complex I is inhibited by rotenone.
Increased ROS would result in oxidative damage to mitochondrial proteins, lipids,
and DNA. CSB appears to behave as an electron scavenger in the mitochondria whose
absence leads to increased oxidative stress. Mitochondrial ROS, however, did not
cause detectable nuclear DNA damage even when base excision repair was blocked by
an inhibitor of polyADP ribose polymerase. Neurodegeneration in Cockayne syndrome
may therefore be associated with ROS-induced damage in the mitochondria,
independent of nuclear TCR. An implication of our present results is that
mitochondrial dysfunction involving ROS has a major impact on CS-B pathology,
whereas nuclear TCR may have a minimal role.
PMID- 25136124
TI - Xylan utilization in human gut commensal bacteria is orchestrated by unique
modular organization of polysaccharide-degrading enzymes.
AB - Enzymes that degrade dietary and host-derived glycans represent the most abundant
functional activities encoded by genes unique to the human gut microbiome.
However, the biochemical activities of a vast majority of the glycan-degrading
enzymes are poorly understood. Here, we use transcriptome sequencing to
understand the diversity of genes expressed by the human gut bacteria Bacteroides
intestinalis and Bacteroides ovatus grown in monoculture with the abundant
dietary polysaccharide xylan. The most highly induced carbohydrate active genes
encode a unique glycoside hydrolase (GH) family 10 endoxylanase (BiXyn10A or
BACINT_04215 and BACOVA_04390) that is highly conserved in the Bacteroidetes
xylan utilization system. The BiXyn10A modular architecture consists of a GH10
catalytic module disrupted by a 250 amino acid sequence of unknown function.
Biochemical analysis of BiXyn10A demonstrated that such insertion sequences
encode a new family of carbohydrate-binding modules (CBMs) that binds to xylose
configured oligosaccharide/polysaccharide ligands, the substrate of the BiXyn10A
enzymatic activity. The crystal structures of CBM1 from BiXyn10A (1.8 A), a
cocomplex of BiXyn10A CBM1 with xylohexaose (1.14 A), and the CBM from its
homolog in the Prevotella bryantii B14 Xyn10C (1.68 A) reveal an unanticipated
mode for ligand binding. A minimal enzyme mix, composed of the gene products of
four of the most highly up-regulated genes during growth on wheat arabinoxylan,
depolymerizes the polysaccharide into its component sugars. The combined
biochemical and biophysical studies presented here provide a framework for
understanding fiber metabolism by an important group within the commensal
bacterial population known to influence human health.
PMID- 25136125
TI - A wave-mechanical model of incoherent quasielastic scattering in complex systems.
AB - Quasielastic incoherent neutron scattering (QENS) is an important tool for the
exploration of the dynamics of complex systems such as biomolecules, liquids, and
glasses. The dynamics is reflected in the energy spectra of the scattered
neutrons. Conventionally these spectra are decomposed into a narrow elastic line
and a broad quasielastic band. The band is interpreted as being caused by Doppler
broadening due to spatial motion of the target molecules. We propose a quantum
mechanical model in which there is no separate elastic line. The quasielastic
band is composed of sharp lines with twice the natural line width, shifted from
the center by a random walk of the protein in the free-energy landscape of the
target molecule. The walk is driven by vibrations and by external fluctuations.
We first explore the model with the Mossbauer effect. In the subsequent
application to QENS we treat the incoming neutron as a de Broglie wave packet.
While the wave packet passes the protons in the protein and the hydration shell
it exchanges energy with the protein during the passage time of about 100 ns. The
energy exchange broadens the ensemble spectrum. Because the exchange involves the
free-energy landscape of the protein, the QENS not only provides insight into the
protein dynamics, but it may also illuminate the free-energy landscape of the
protein-solvent system.
PMID- 25136126
TI - A unique PDZ domain and arrestin-like fold interaction reveals mechanistic
details of endocytic recycling by SNX27-retromer.
AB - The sorting nexin 27 (SNX27)-retromer complex is a major regulator of endosome-to
plasma membrane recycling of transmembrane cargos that contain a PSD95, Dlg1, zo
1 (PDZ)-binding motif. Here we describe the core interaction in SNX27-retromer
assembly and its functional relevance for cargo sorting. Crystal structures and
NMR experiments reveal that an exposed beta-hairpin in the SNX27 PDZ domain
engages a groove in the arrestin-like structure of the vacuolar protein sorting
26A (VPS26A) retromer subunit. The structure establishes how the SNX27 PDZ domain
simultaneously binds PDZ-binding motifs and retromer-associated VPS26.
Importantly, VPS26A binding increases the affinity of the SNX27 PDZ domain for
PDZ- binding motifs by an order of magnitude, revealing cooperativity in cargo
selection. With disruption of SNX27 and retromer function linked to synaptic
dysfunction and neurodegenerative disease, our work provides the first step, to
our knowledge, in the molecular description of this important sorting complex,
and more broadly describes a unique interaction between a PDZ domain and an
arrestin-like fold.
PMID- 25136127
TI - A sharp T-cell antigen receptor signaling threshold for T-cell proliferation.
AB - T-cell antigen receptor (TCR) signaling is essential for activation,
proliferation, and effector function of T cells. Modulation of both intensity and
duration of TCR signaling can regulate these events. However, it remains unclear
how individual T cells integrate such signals over time to make critical cell
fate decisions. We have previously developed an engineered mutant allele of the
critical T-cell kinase zeta-chain-associated protein kinase 70 kDa (Zap70) that
is catalytically inhibited by a small molecule inhibitor, thereby blocking TCR
signaling specifically and efficiently. We have also characterized a fluorescent
reporter Nur77-eGFP transgenic mouse line in which T cells up-regulate GFP
uniquely in response to TCR stimulation. The combination of these technologies
unmasked a sharp TCR signaling threshold for commitment to cell division both in
vitro and in vivo. Further, we demonstrate that this threshold is independent of
both the magnitude of the TCR stimulus and Interleukin 2. Similarly, we identify
a temporal threshold of TCR signaling that is required for commitment to
proliferation, after which T cells are able to proliferate in a Zap70 kinase
independent manner. Taken together, our studies reveal a sharp threshold for the
magnitude and duration of TCR signaling required for commitment of T cells to
proliferation. These results have important implications for understanding T-cell
responses to infection and optimizing strategies for immunomodulatory drug
delivery.
PMID- 25136128
TI - A lipid zipper triggers bacterial invasion.
AB - Glycosphingolipids are important structural constituents of cellular membranes.
They are involved in the formation of nanodomains ("lipid rafts"), which serve as
important signaling platforms. Invasive bacterial pathogens exploit these
signaling domains to trigger actin polymerization for the bending of the plasma
membrane and the engulfment of the bacterium--a key process in bacterial uptake.
However, it is unknown whether glycosphingolipids directly take part in the
membrane invagination process. Here, we demonstrate that a "lipid zipper," which
is formed by the interaction between the bacterial surface lectin LecA and its
cellular receptor, the glycosphingolipid Gb3, triggers plasma membrane bending
during host cell invasion of the bacterium Pseudomonas aeruginosa. In vitro
experiments with Gb3-containing giant unilamellar vesicles revealed that LecA/Gb3
mediated lipid zippering was sufficient to achieve complete membrane engulfment
of the bacterium. In addition, theoretical modeling elucidated that the adhesion
energy of the LecA-Gb3 interaction is adequate to drive the engulfment process.
In cellulo experiments demonstrated that inhibition of the LecA/Gb3 lipid zipper
by either lecA knockout, Gb3 depletion, or application of soluble sugars that
interfere with LecA binding to Gb3 significantly lowered P. aeruginosa uptake by
host cells. Of note, membrane engulfment of P. aeruginosa occurred independently
of actin polymerization, thus corroborating that lipid zippering alone is
sufficient for this crucial first step of bacterial host-cell entry. Our study
sheds new light on the impact of glycosphingolipids in the cellular invasion of
bacterial pathogens and provides a mechanistic explication of the initial uptake
processes.
PMID- 25136129
TI - Valuing vaccination.
AB - Vaccination has led to remarkable health gains over the last century. However,
large coverage gaps remain, which will require significant financial resources
and political will to address. In recent years, a compelling line of inquiry has
established the economic benefits of health, at both the individual and aggregate
levels. Most existing economic evaluations of particular health interventions
fail to account for this new research, leading to potentially sizable
undervaluation of those interventions. In line with this new research, we set
forth a framework for conceptualizing the full benefits of vaccination, including
avoided medical care costs, outcome-related productivity gains, behavior-related
productivity gains, community health externalities, community economic
externalities, and the value of risk reduction and pure health gains. We also
review literature highlighting the magnitude of these sources of benefit for
different vaccinations. Finally, we outline the steps that need to be taken to
implement a broad-approach economic evaluation and discuss the implications of
this work for research, policy, and resource allocation for vaccine development
and delivery.
PMID- 25136130
TI - Vaccines, new opportunities for a new society.
AB - Vaccination is the most effective medical intervention ever introduced and,
together with clean water and sanitation, it has eliminated a large part of the
infectious diseases that once killed millions of people. A recent study concluded
that since 1924 in the United States alone, vaccines have prevented 40 million
cases of diphtheria, 35 million cases of measles, and a total of 103 million
cases of childhood diseases. A report from the World Health Organization states
that today vaccines prevent 2.5 million deaths per year: Every minute five lives
are saved by vaccines worldwide. Overall, vaccines have done and continue to do
an excellent job in eliminating or reducing the impact of childhood diseases.
Furthermore, thanks to new technologies, vaccines now have the potential to make
an enormous contribution to the health of modern society by preventing and
treating not only communicable diseases in all ages, but also noncommunicable
diseases such as cancer and neurodegenerative disorders. The achievement of these
results requires the development of novel technologies and health economic models
able to capture not only the mere cost-benefit of vaccination, but also the value
of health per se.
PMID- 25136131
TI - Efficient biomass pretreatment using ionic liquids derived from lignin and
hemicellulose.
AB - Ionic liquids (ILs), solvents composed entirely of paired ions, have been used in
a variety of process chemistry and renewable energy applications. Imidazolium
based ILs effectively dissolve biomass and represent a remarkable platform for
biomass pretreatment. Although efficient, imidazolium cations are expensive and
thus limited in their large-scale industrial deployment. To replace imidazolium
based ILs with those derived from renewable sources, we synthesized a series of
tertiary amine-based ILs from aromatic aldehydes derived from lignin and
hemicellulose, the major by-products of lignocellulosic biofuel production.
Compositional analysis of switchgrass pretreated with ILs derived from vanillin,
p-anisaldehyde, and furfural confirmed their efficacy. Enzymatic hydrolysis of
pretreated switchgrass allowed for direct comparison of sugar yields and lignin
removal between biomass-derived ILs and 1-ethyl-3-methylimidazolium acetate.
Although the rate of cellulose hydrolysis for switchgrass pretreated with biomass
derived ILs was slightly slower than that of 1-ethyl-3-methylimidazolium acetate,
90-95% glucose and 70-75% xylose yields were obtained for these samples after 72
h incubation. Molecular modeling was used to compare IL solvent parameters with
experimentally obtained compositional analysis data. Effective pretreatment of
lignocellulose was further investigated by powder X-ray diffraction and glycome
profiling of switchgrass cell walls. These studies showed different cellulose
structural changes and differences in hemicellulose epitopes between switchgrass
pretreatments with the aforementioned ILs. Our concept of deriving ILs from
lignocellulosic biomass shows significant potential for the realization of a
"closed-loop" process for future lignocellulosic biorefineries and has far
reaching economic impacts for other IL-based process technology currently using
ILs synthesized from petroleum sources.
PMID- 25136132
TI - (R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity
in cells.
AB - SET domain containing (lysine methyltransferase) 7 (SETD7) is implicated in
multiple signaling and disease related pathways with a broad diversity of
reported substrates. Here, we report the discovery of (R)-PFI-2-a first-in-class,
potent (Ki (app) = 0.33 nM), selective, and cell-active inhibitor of the
methyltransferase activity of human SETD7-and its 500-fold less active
enantiomer, (S)-PFI-2. (R)-PFI-2 exhibits an unusual cofactor-dependent and
substrate-competitive inhibitory mechanism by occupying the substrate peptide
binding groove of SETD7, including the catalytic lysine-binding channel, and by
making direct contact with the donor methyl group of the cofactor, S
adenosylmethionine. Chemoproteomics experiments using a biotinylated derivative
of (R)-PFI-2 demonstrated dose-dependent competition for binding to endogenous
SETD7 in MCF7 cells pretreated with (R)-PFI-2. In murine embryonic fibroblasts,
(R)-PFI-2 treatment phenocopied the effects of Setd7 deficiency on Hippo pathway
signaling, via modulation of the transcriptional coactivator Yes-associated
protein (YAP) and regulation of YAP target genes. In confluent MCF7 cells, (R)
PFI-2 rapidly altered YAP localization, suggesting continuous and dynamic
regulation of YAP by the methyltransferase activity of SETD7. These data
establish (R)-PFI-2 and related compounds as a valuable tool-kit for the study of
the diverse roles of SETD7 in cells and further validate protein
methyltransferases as a druggable target class.
PMID- 25136133
TI - Unleashing the potential of NOD- and Toll-like agonists as vaccine adjuvants.
AB - Innate immunity confers an immediate nonspecific mechanism of microbial
recognition through germ line-encoded pattern recognition receptors (PRRs). Of
these, Toll-like receptors (TLRs) and nucleotide-binding and oligomerization
domain (NOD)-like receptors (NLRs) have shaped our current understanding of
innate regulation of adaptive immunity. It is now recognized that PRRs are
paramount in instructing an appropriate adaptive immune response. Their ligands
have been the focus of adjuvant research with the goal of generating modern
vaccine combinations tailored to specific pathogens. In this review we will
highlight the recent findings in the field of adjuvant research with a particular
focus on the potential of TLR and NLR ligands as adjuvants and their influence on
adaptive immune responses.
PMID- 25136134
TI - History of vaccination.
AB - Vaccines have a history that started late in the 18th century. From the late 19th
century, vaccines could be developed in the laboratory. However, in the 20th
century, it became possible to develop vaccines based on immunologic markers. In
the 21st century, molecular biology permits vaccine development that was not
possible before.
PMID- 25136136
TI - Local anesthetic and antiepileptic drug access and binding to a bacterial voltage
gated sodium channel.
AB - Voltage-gated sodium (Nav) channels are important targets in the treatment of a
range of pathologies. Bacterial channels, for which crystal structures have been
solved, exhibit modulation by local anesthetic and anti-epileptic agents,
allowing molecular-level investigations into sodium channel-drug interactions.
These structures reveal no basis for the "hinged lid"-based fast inactivation,
seen in eukaryotic Nav channels. Thus, they enable examination of potential
mechanisms of use- or state-dependent drug action based on activation gating, or
slower pore-based inactivation processes. Multimicrosecond simulations of NavAb
reveal high-affinity binding of benzocaine to F203 that is a surrogate for FS6,
conserved in helix S6 of Domain IV of mammalian sodium channels, as well as low
affinity sites suggested to stabilize different states of the channel. Phenytoin
exhibits a different binding distribution owing to preferential interactions at
the membrane and water-protein interfaces. Two drug-access pathways into the pore
are observed: via lateral fenestrations connecting to the membrane lipid phase,
as well as via an aqueous pathway through the intracellular activation gate,
despite being closed. These observations provide insight into drug modulation
that will guide further developments of Nav inhibitors.
PMID- 25136135
TI - Loss of Miro1-directed mitochondrial movement results in a novel murine model for
neuron disease.
AB - Defective mitochondrial distribution in neurons is proposed to cause ATP
depletion and calcium-buffering deficiencies that compromise cell function.
However, it is unclear whether aberrant mitochondrial motility and distribution
alone are sufficient to cause neurological disease. Calcium-binding mitochondrial
Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and
retrograde transport in neurons. Using two new KO mouse models, we demonstrate
that Miro1 is essential for development of cranial motor nuclei required for
respiratory control and maintenance of upper motor neurons required for
ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from
corticospinal tract axons and progressive neurological deficits mirroring human
upper motor neuron disease. Although Miro1-deficient neurons exhibit defects in
retrograde axonal mitochondrial transport, mitochondrial respiratory function
continues. Moreover, Miro1 is not essential for calcium-mediated inhibition of
mitochondrial movement or mitochondrial calcium buffering. Our findings indicate
that defects in mitochondrial motility and distribution are sufficient to cause
neurological disease.
PMID- 25136138
TI - Demographic characteristics of doctors who intend to follow clinical academic
careers: UK national questionnaire surveys.
AB - OBJECTIVES: It is well recognised that women are underrepresented in clinical
academic posts. Our aim was to determine which of a number of characteristics
notably gender, but also ethnicity, possession of an intercalated degree, medical
school attended, choice of specialty-were predictive of doctors' intentions to
follow clinical academic careers. DESIGN: Questionnaires to all UK-trained
medical graduates of 2005 sent in 2006 and again in 2010, graduates of 2009 in
2010 and graduates of 2012 in 2013. RESULTS: At the end of their first year of
medical work, 13.5% (368/2732) of men and 7.3% (358/4891) of women specified that
they intended to apply for a clinical academic training post; and 6.0% (172/2873)
of men and 2.2% (111/5044) of women specified that they intended to pursue
clinical academic medicine as their eventual career. A higher percentage of Asian
(4.8%) than White doctors (3.3%) wanted a long-term career as a clinical
academic, as did a higher percentage of doctors who did an intercalated degree
(5.6%) than others (2.2%) and a higher percentage of Oxbridge graduates (8.1%)
than others (2.8%). Of the graduates of 2005, only 30% of those who in 2006
intended a clinical medicine career also did so when re-surveyed in 2010 (men
44%, women 12%). CONCLUSIONS: There are noteworthy differences by gender and
other demographic factors in doctors' intentions to pursue academic training and
careers. The gap between men and women in aspirations for a clinical academic
career is present as early as the first year after qualification.
PMID- 25136137
TI - Endothelial Akt1 mediates angiogenesis by phosphorylating multiple angiogenic
substrates.
AB - The PI3K/Akt pathway is necessary for several key endothelial cell (EC)
functions, including cell growth, migration, survival, and vascular tone.
However, existing literature supports the idea that Akt can be either pro- or
antiangiogenic, possibly due to compensation by multiple isoforms in the EC when
a single isoform is deleted. Thus, biochemical, genetic, and proteomic studies
were conducted to examine isoform-substrate specificity for Akt1 vs. Akt2. In
vitro, Akt1 preferentially phosphorylates endothelial nitric oxide synthase
(eNOS) and promotes NO release, whereas nonphysiological overexpression of Akt2
can bypass the loss of Akt1. Conditional deletion of Akt1 in the EC, in the
absence or presence of Akt2, retards retinal angiogenesis, implying that Akt1
exerts a nonredundant function during physiological angiogenesis. Finally,
proteomic analysis of Akt substrates isolated from Akt1- or Akt2-deficient ECs
documents that phosphorylation of multiple Akt substrates regulating angiogenic
signaling is reduced in Akt1-deficient, but not Akt2-deficient, ECs, including
eNOS and Forkhead box proteins. Therefore, Akt1 promotes angiogenesis largely due
to phosphorylation and regulation of important downstream effectors that promote
aspects of angiogenic signaling.
PMID- 25136139
TI - Patients as teachers: a randomised controlled trial on the use of personal
stories of harm to raise awareness of patient safety for doctors in training.
AB - BACKGROUND: Patient safety training often provides learners with a health
professional's perspective rather than the patient's. Personal narratives of
health-related harm allow patients to share their stories with health
professionals to influence clinical behaviour by rousing emotions and improving
attitudes to safety. AIM: This study measured the impact of patient narratives
used to train junior doctors in patient safety. METHODS: An open, multi-centre,
two-arm, parallel design randomised controlled trial was conducted in the North
Yorkshire East Coast Foundation School (NYECFS). The intervention consisted of 1
h-long patient narratives followed by discussion. The control arm received
conventional faculty-delivered teaching. The Attitude to Patient Safety
Questionnaire (APSQ) and the Positive and Negative Affect Schedule (PANAS) were
used to measure the impact of the intervention. RESULTS: 142 trainees received
the intervention; 141 the control teaching. There was no evidence of a difference
in post-intervention APSQ scores between the groups. There was a statistically
significant difference in the underlying distribution of both post PA (positive
affect) and post NA (negative affect) scores between the groups on the PANAS
(p<0.001) with indications of both higher PA and NA scores in the intervention
group. CONCLUSIONS: Involving patients with experiences of safety incidents in
training has an ideological appeal and seems an obvious choice in designing
safety interventions. On the basis of our primary outcome measure, we were unable
to demonstrate effectiveness of the intervention in changing general attitudes to
safety compared to control. While the intervention may impact on emotional
engagement and learning about communication, we remain uncertain whether this
will translate into improved behaviours in the clinical context or indeed if
there are any negative effects. TRIAL REGISTRATION NUMBER: Grant reference no. RP
PG-0108-10049.
PMID- 25136140
TI - Evaluation of hospital factors associated with hospital postoperative venous
thromboembolism imaging utilisation practices.
AB - BACKGROUND: Recent research suggests that hospital rates of postoperative venous
thromboembolism (VTE) are subject to surveillance bias: the more hospitals 'look
for' VTE, the more VTE they find. However, little is known about what drives
variation in hospital VTE imaging rates. We conducted an observational study to
examine hospital and market characteristics that were associated with hospital
level rates of postoperative VTE imaging, focusing on hospitals with particularly
high rates. METHODS: For Medicare beneficiaries undergoing 11 major operations
(2009-2010) at 2820 hospitals, hospital-level postoperative VTE imaging use rates
were calculated. Hospital characteristics associated with hospital VTE imaging
use rates were examined including case severity, size, ownership, VTE process
measure adherence, accreditations, staffing, malpractice environment, and county
market factors. Associations between explanatory variables and VTE imaging rates
were assessed using quantile regressions at the 25th, median, 75th and 90th
quantiles. RESULTS: Mean postoperative VTE imaging rates ranged from 85.26
(SD=67.38) per 1000 discharges in the lowest quartile of hospitals ranked by VTE
imaging rates to 168.86 (SD=76.70) in the highest quartile. Drivers of high
imaging rates at the 90th quantile were high resident-to-bed ratio
(coefficient=51.35, p<0.01), Joint Commission accreditation (coefficient=19.05,
p<0.01), presence of other hospitals in the same market with high imaging rates
(coefficient=15.29, p<0.01), average case severity (coefficient=11.97, p<0.01),
local malpractice costs (coefficient=11.29, p<0.01), and market competition
(coefficient=11.03, p<0.01). CONCLUSIONS: Hospital teaching status, resident-to
bed ratio, malpractice environment and local market factors drive hospital
postoperative VTE imaging use, suggesting that non-clinical forces predominantly
drive hospital VTE imaging practices.
PMID- 25136142
TI - Family Economic Strengthening and Parenting Stress Among Caregivers of AIDS
Orphaned Children: Results from a Cluster Randomized Clinical Trial in Uganda.
AB - This study examines the impact of a family economic strengthening intervention on
parenting stress among caregivers of AIDS-orphaned children in Uganda. The study
uses data from a 4-year (2008-2012) NIMH randomized clinical trial for AIDS
orphaned children known as Suubi-Maka (N=346 dyads). Child-caregiver dyads from
10 comparable primary schools were randomly assigned to either the control group
(n=167 dyads) receiving usual care for school-going orphaned children (such as
food aid and scholastic materials) or the treatment group (n=179 dyads) receiving
a family economic strengthening intervention (focused on a matched savings
account), financial planning and management workshops over and above the usual
care. Interviews were conducted at baseline, 12 months and 24 months follow-up.
This study uses data from baseline and 24 months post-intervention. We use
multivariate regression methods, controlling for socioeconomic characteristics.
At 24 months, caregivers in the treatment group reported significantly lower
levels of parenting stress compared to caregivers in the control group. Findings
from this study point to the potential of a family economic strengthening
intervention to improve caregiver's psychosocial wellbeing and that of their
families. We conclude that programs and policies aimed at improving the
psychosocial wellbeing of families caring for AIDS-orphaned children may consider
incorporating economic strengthening components in their programming to help
support these kinds of families, caregivers of AIDS-orphaned children especially
those residing in developing countries.
PMID- 25136141
TI - Learning from mistakes in clinical practice guidelines: the case of perioperative
beta-blockade.
PMID- 25136143
TI - The effect of a community-based, primary health care exercise program on
inflammatory biomarkers and hormone levels.
AB - The aim of this study was to analyze the impact of a community-based exercise
program in primary care on inflammatory biomarkers and hormone levels. The 1-year
quasiexperimental study involved 13 women (mean age = 56.8 +/- 11.4 years) and it
was developed in two basic health care units in Rio Claro City, Brazil. The
physical exercise intervention was comprised of two, 60-minute sessions/week. The
inflammatory biomarkers were measured at baseline, 6 months, and 1 year. Repeated
measures ANOVA analyses indicated that the intervention was effective in reducing
CRP and TNFalpha after 1 year compared to baseline and 6 months (P < 0.05). There
were no changes in IL10, IL6, and insulin after 1 year. However, leptin
significantly increased at 1 year (P = 0.016). The major finding of this study is
that a community-based exercise program can result in a decrease or maintenance
of inflammatory biomarkers after 1 year, and thus has the potential to be a
viable public health approach for chronic disease prevention.
PMID- 25136145
TI - The Wnt/beta-catenin signaling pathway controls the inflammatory response in
infections caused by pathogenic bacteria.
AB - Innate immunity against pathogenic bacteria is critical to protect host cells
from invasion and infection as well as to develop an appropriate adaptive immune
response. During bacterial infection, different signaling transduction pathways
control the expression of a wide range of genes that orchestrate a number of
molecular and cellular events to eliminate the invading microorganisms and
regulate inflammation. The inflammatory response must be tightly regulated
because uncontrolled inflammation may lead to tissue injury. Among the many
signaling pathways activated, the canonical Wnt/beta-catenin has been recently
shown to play an important role in the expression of several inflammatory
molecules during bacterial infections. Our main goal in this review is to discuss
the mechanism used by several pathogenic bacteria to modulate the inflammatory
response through the Wnt/beta-catenin signaling pathway. We think that a deep
insight into the role of Wnt/beta-catenin signaling in the inflammation may open
new venues for biotechnological approaches designed to control bacterial
infectious diseases.
PMID- 25136144
TI - Immunologic biomarkers for clinical and therapeutic management of psoriasis.
AB - BACKGROUND: The therapeutic management of psoriasis includes conventional
treatments as well as the new generation of highly effective TNF-alpha
inhibitors. However, psoriasis has proven to be a complex therapeutic challenge
and treatment failures are not uncommon. Thus, laboratory biomarkers of disease
progression/therapeutic efficacy may greatly help in the clinical management of
psoriasis. AIMS: To identify laboratory biomarkers for clinical management and
therapeutic monitoring of psoriasis. METHODS: An observational study performed on
59 patients, presenting moderate to severe psoriasis, undergoing treatment with
anti-TNF-alpha agents (etanercept, adalimumab, and infliximab). Soluble and
cellular immune/inflammatory parameters were assessed at baseline and after 12
and 24 weeks of treatment. RESULTS: Clinical efficacy was achieved in 88% of the
subjects at 12 weeks, reaching 90% after 24 weeks. IL-6 and IL-22, which were
elevated at baseline, were significantly reduced, in association with a
significant decrease of CLA+ T cells and an increase of Treg lymphocytes. T, B,
and NK cell subsets and T cell response to recall antigens did not show any
evidence of immune suppression. CONCLUSIONS: Immune/inflammatory parameters
including IL-6 and IL-22, CLA+ T cells, and Treg lymphocytes may prove to be
valuable laboratory tools for the clinical and therapeutic monitoring of
psoriasis.
PMID- 25136146
TI - IL-17 genetic and immunophenotypic evaluation in chronic graft-versus-host
disease.
AB - Although interleukin-17 (IL-17) is a recently discovered cytokine associated with
several autoimmune diseases, its role in the pathogenesis of chronic graft-versus
host disease (cGVHD) was not established yet. The objective of this study was to
investigate the association of IL17A and IL17F genes polymorphisms and IL-17A and
IL-17F levels with cGVHD. IL-17A expression was also investigated in CD4(+) T
cells of patients with systemic cGVHD. For Part I of the study, fifty-eight allo
HSCT recipients and donors were prospectively studied. Blood samples were
obtained to determine IL17A and IL17F genes polymorphisms. Cytokines levels in
blood and saliva were assessed by ELISA at days +35 and +100 after HSCT. In Part
II, for the immunophenotypic evaluation, eight patients with systemic cGVHD were
selected and the expression of IL-17A was evaluated. We found association between
recipient AA genotype with systemic cGVHD. No association was observed between IL
17A levels and cGVHD. Lower IL-17A levels in the blood were associated with AA
genotype. In flow cytometry analysis, decreased expression of IL-17A was observed
in patients with cGVHD after stimulation. In conclusion, IL-17A may have an
important role in the development of systemic cGVHD.
PMID- 25136147
TI - Intraperitoneal infusion of mesenchymal stem/stromal cells prevents experimental
autoimmune uveitis in mice.
AB - Autoimmune uveitis is one of the leading causes of blindness. We here
investigated whether intraperitoneal administration of human mesenchymal
stem/stromal cells (hMSCs) might prevent development of experimental autoimmune
uveitis (EAU) in mice. Time course study showed that the number of IFN-gamma- or
IL-17-expressing CD4(+) T cells was increased in draining lymph nodes (DLNs) on
the postimmunization day 7 and decreased thereafter. The retinal structure was
severely disrupted on day 21. An intraperitoneal injection of hMSCs at the time
of immunization protected the retina from damage and suppressed the levels of
proinflammatory cytokines in the eye. Analysis of DLNs on day 7 showed that hMSCs
decreased the number of Th1 and Th17 cells. The hMSCs did not reduce the levels
of IL-1beta, IL-6, IL-12, and IL-23 which are the cytokines that drive Th1/Th17
differentiation. Also, hMSCs did not induce CD4(+)CD25(+)Foxp3(+) cells. However,
hMSCs increased the level of an immunoregulatory cytokine IL-10 and the
population of IL-10-expressing B220(+)CD19(+) cells. Together, data demonstrate
that hMSCs attenuate EAU by suppressing Th1/Th17 cells and induce IL-10
expressing B220(+)CD19(+) cells. Our results support suggestions that hMSCs may
offer a therapy for autoimmune diseases mediated by Th1/Th17 responses.
PMID- 25136150
TI - Healthcare as an electoral agenda.
PMID- 25136151
TI - Achieving universal health coverage through community empowerment: a proposition
for bangladesh.
PMID- 25136148
TI - Switching off key signaling survival molecules to switch on the resolution of
inflammation.
AB - Inflammation is a physiological response of the immune system to injury or
infection but may become chronic. In general, inflammation is self-limiting and
resolves by activating a termination program named resolution of inflammation. It
has been argued that unresolved inflammation may be the basis of a variety of
chronic inflammatory diseases. Resolution of inflammation is an active process
that is fine-tuned by the production of proresolving mediators and the shutdown
of intracellular signaling molecules associated with cytokine production and
leukocyte survival. Apoptosis of leukocytes (especially granulocytes) is a key
element in the resolution of inflammation and several signaling molecules are
thought to be involved in this process. Here, we explore key signaling molecules
and some mediators that are crucial regulators of leukocyte survival in vivo and
that may be targeted for therapeutic purposes in the context of chronic
inflammatory diseases.
PMID- 25136149
TI - Antagonizing arachidonic acid-derived eicosanoids reduces inflammatory Th17 and
Th1 cell-mediated inflammation and colitis severity.
AB - During colitis, activation of two inflammatory T cell subsets, Th17 and Th1
cells, promotes ongoing intestinal inflammatory responses. n-6 polyunsaturated
fatty acid- (PUFA-) derived eicosanoids, such as prostaglandin E2 (PGE2), promote
Th17 cell-mediated inflammation, while n-3 PUFA antagonize both Th17 and Th1
cells and suppress PGE2 levels. We utilized two genetic mouse models, which
differentially antagonize PGE2 levels, to examine the effect on Th17 cells and
disease outcomes in trinitrobenzene sulfonic acid- (TNBS-) induced colitis. Fat-1
mice contain the omega3 desaturase gene from C. elegans and synthesize n-3 PUFA
de novo, thereby reducing the biosynthesis of n-6 PUFA-derived eicosanoids. In
contrast, Fads1 Null mice contain a disrupted Delta5 desaturase gene and produce
lower levels of n-6 PUFA-derived eicosanoids. Compared to Wt littermates, Fat-1
and Fads1 Null mice exhibited a similar colitic phenotype characterized by
reduced colonic mucosal inflammatory eicosanoid levels and mRNA expression of
Th17 cell markers (IL-17A, RORgammatau, and IL-23), decreased percentages of Th17
cells and, improved colon injury scores (P <= 0.05). Thus, during colitis,
similar outcomes were obtained in two genetically distinct models, both of which
antagonize PGE2 levels via different mechanisms. Our data highlight the critical
impact of n-6 PUFA-derived eicosanoids in the promotion of Th17 cell-mediated
colonic inflammation.
PMID- 25136153
TI - Managing self for leadership.
PMID- 25136152
TI - Maternal near miss: an indicator for maternal health and maternal care.
AB - Maternal mortality is one of the important indicators used for the measurement of
maternal health. Although maternal mortality ratio remains high, maternal deaths
in absolute numbers are rare in a community. To overcome this challenge, maternal
near miss has been suggested as a compliment to maternal death. It is defined as
pregnant or recently delivered woman who survived a complication during
pregnancy, childbirth or 42 days after termination of pregnancy. So far various
nomenclature and criteria have been used to identify maternal near-miss cases and
there is lack of uniform criteria for identification of near miss. The World
Health Organization recently published criteria based on markers of management
and organ dysfunction, which would enable systematic data collection on near miss
and development of summary estimates. The prevalence of near miss is higher in
developing countries and causes are similar to those of maternal mortality namely
hemorrhage, hypertensive disorders, sepsis and obstructed labor. Reviewing near
miss cases provide significant information about the three delays in health
seeking so that appropriate action is taken. It is useful in identifying health
system failures and assessment of quality of maternal health-care. Certain
maternal near miss indicators have been suggested to evaluate the quality of
care. The near miss approach will be an important tool in evaluation and
assessment of the newer strategies for improving maternal health.
PMID- 25136154
TI - A Clinical Study of Vitiligo in a Rural Set up of Gujarat.
AB - INTRODUCTION: Vitiligo is an acquired depigmentary condition caused by
inactivation or destruction of melanocytes in epidermis and hair follicle.
Worldwide incidence of 1% has been reported; similar to various dermatological
clinics in India. Widespread prejudice, ignorance, taboos, lack of scientific
appraisal, and confusion of vitiligo with leprosy makes it an immense
psychological stress. AIM: To know the clinical profile of vitiligo patient with
associated cofactors. MATERIALS AND METHODS: Total 1,010 patients of vitiligo
attended in outpatient department at Shree Krishna Hospital (SKH) and Matar camp,
Gujarat over 1 year period from August 2011 to July 2012 were included in this
study. Detail history and clinical examination of patients were done. RESULTS:
Out of 1,010 patients 57.3% were females and 42.7 % were males. Most cases
developed vitiligo by 2(nd) decade of life. Progressive course was found in 60.9
% of patients. Vitiligo vulgaris (57.8%) was most common morphological type. Most
common site of onset (41.5%) and involvement (75.7%) was lower limb. Family
history was present in 20.4%. CONCLUSIONS: Vitiligo constitutes important
dermatological disease especially in India. The data suggest that local
epidemiological behavior of vitiligo need not be the same across different
regions. Vitiligo differs substantially in various clinical aspects.
PMID- 25136155
TI - Challenges in Developing Competency-based Training Curriculum for Food Safety
Regulators in India.
AB - CONTEXT: The Food Safety and Standards Act have redefined the roles and
responsibilities of food regulatory workforce and calls for highly skilled human
resources as it involves complex management procedures. AIMS: 1) Identify the
competencies needed among the food regulatory workforce in India. 2) Develop a
competency-based training curriculum for food safety regulators in the country.
3) Develop training materials for use to train the food regulatory workforce.
SETTINGS AND DESIGN: The Indian Institute of Public Health, Hyderabad, led the
development of training curriculum on food safety with technical assistance from
the Royal Society for Public Health, UK and the National Institute of Nutrition,
India. The exercise was to facilitate the implementation of new Act by
undertaking capacity building through a comprehensive training program. MATERIALS
AND METHODS: A competency-based training needs assessment was conducted before
undertaking the development of the training materials. RESULTS: THE TRAINING
PROGRAM FOR FOOD SAFETY OFFICERS WAS DESIGNED TO COMPRISE OF FIVE MODULES TO
INCLUDE: Food science and technology, Food safety management systems, Food safety
legislation, Enforcement of food safety regulations, and Administrative
functions. Each module has a facilitator guide for the tutor and a handbook for
the participant. Essentials of Food Hygiene-I (Basic level), II and III (Retail/
Catering/ Manufacturing) were primarily designed for training of food handlers
and are part of essential reading for food safety regulators. CONCLUSION: The
Food Safety and Standards Act calls for highly skilled human resources as it
involves complex management procedures. Despite having developed a comprehensive
competency-based training curriculum by joint efforts by the local, national, and
international agencies, implementation remains a challenge in resource-limited
setting.
PMID- 25136156
TI - Antibiotic susceptibility profile of bacteria isolated from natural sources of
water from rural areas of East sikkim.
AB - BACKGROUND: Contamination of water, food, and environment with antibiotic
resistant bacteria poses a serious public health issue. OBJECTIVE: The objective
was to study the bacterial pollution of the natural sources of water in east
Sikkim and to determine the antimicrobial profile of the bacterial isolates.
MATERIALS AND METHODS: A total of 225 samples, 75 each during winter, summer, and
monsoon season were collected from the same source in every season for
bacteriological analysis by membrane filtration method. Antibiotic susceptibility
test was performed using standard disc diffusion method. RESULTS: A total of 19
bacterial species of the genera Escherichia, Klebsiella, Proteus, Salmonella,
Shigella, Enterobacter, Citrobacter, Morganella, Pseudomonas, Acinetobacter,
Flavobacterium, and Serratia were isolated and their antimicrobial sensitivity
tested. Generally, most bacterial isolates except Salmonella and Shigella species
were found resistant to commonly used antibiotics such as ampicillin (57.5%),
trimethoprim/sulfamethoxaole (39.1%), amoxicillin/clavulanic acid (37.4%),
cefixime (34.5%), tetracycline (29.1%), ceftazidime (26.3%), ofloxacin (25.9%),
amikacin (8.7%), and gentamicin (2.7%) but sensitive to imipenem and
piperacillin/tazobactam. CONCLUSION: Natural sources of water in east Sikkim are
grossly contaminated with bacteria including enteropathogens. The consumption of
untreated water from these sources might pose health risk to consumers.
PMID- 25136157
TI - Anthropometric and Nutritional Profile of People Living with HIV and AIDS in
India: an Assessment.
AB - BACKGROUND: Importance of nutrition in human immunodeficiency virus (HIV) is well
established; however, the information regarding the diet quality of people living
with HIV (PLHIV) especially in India is lacking. OBJECTIVES: The objective of
this study is to assess the anthropometric and nutritional profile of Indian
PLHIV. MATERIAL AND METHODS: The study was performed on 400 adult PLHIV
registered at the Antiretroviral Center (ART) center in New Delhi, India.
Anthropometric data including height, weight, waist, hip, mid arm, and calf
circumferences, were collected; 1-day 24-h dietary recall was done to gather
nutrient intake from which nutrient adequacy ratios were computed. Mini
Nutritional Assessment (MNA) was also conducted. RESULTS: The mean body mass
index (BMI) of the sample was 19.73 +/- 3.55 kg/m(2) with around 40% having BMI
<18.5 kg/m(2) . All anthropometric measurements were found to correlate
positively and significantly with CD4 count (P < 0.05). The sample consumed poor
quality of diet as they could not meet even the 2/3(rd) of the Indian Council of
Medical Research (2010) requirements for energy, protein, calcium, iron,
riboflavin, niacin, folic acid, B12, copper, and zinc. Classification of subjects
according to MNA indicated that more than 50% of the sample was at-risk of
malnutrition and 34% were malnourished. With 40% of sample having BMI less than
normal, 50% at risk of malnutrition together with poor nutrient intakes over a
long period of time could contribute to further worsening of the nutritional
status. CONCLUSION: There is a need to develop a database on nutritional profile
of PLHIV in India which reinforces the need for development of effective
strategies to improve their nutritional status.
PMID- 25136158
TI - Nutritional Status of under 5 Children belonging to Tribal Population Living in
Riverine (Char) Areas of Dibrugarh District, Assam.
AB - CONTEXT: Assam's main lifeline, the Brahmaputra river, braided nature created
numerous sand bars and islands known as chars/sapories. They are home to more
than 3 million people. Over 90% of the cultivated land on the river islands is
flood-prone; the flood leaves the islands completely separated from mainland,
preventing access to health infrastructure and services. AIMS: To assess the
nutritional status of under 5 children residing in the char areas of Dibrugarh
district and to identify the factors influencing their nutritional status.
SETTINGS AND DESIGN: A community-based cross-sectional study conducted in the
riverine areas of Dibrugarh district of Assam. MATERIALS AND METHODS: Nutritional
status was assessed using anthropometry. Undernutrition was classified using
World Health Organization (WHO) recommended Z- score system. Data collection was
done by house to house visit of all chars using proportionate allocation.
STATISTICAL ANALYSIS USED: Rates, ratios, proportions, and chi-square test.
RESULTS: Overall prevalence of underweight, stunting, and wasting was 29%, 30.4%,
and 21.6%, respectively. Prevalence of underweight and stunting was less than the
prevalence of underweight (36.4%) and stunting (46.5%) in Assam, but the
prevalence of wasting was more than that of Assam (13.7%) as observed in National
Family Health Survey-3. Significant association was observed between the
prevalence of undernutrition and socioeconomic status, literacy status of
parents, infant, and young child feeding practices and size of the family (P <
0.05). CONCLUSIONS: Special focus is needed for nutritional improvement of under
5 living in char areas to prevent preventable morbidities and to achieve optimum
development.
PMID- 25136159
TI - Health issues amongst call center employees, an emerging occupational group in
India.
AB - Call center sector in India is a relatively new industry and one of the fastest
growing sectors driving employment and growth in modern India today. While
employment in the business process outsourcing (BPO) sector has meant that young
adults are reaching their career milestones and financial goals much earlier than
before, surveys and anecdotal evidence show that workers in the BPO sector
experience high levels of stress and its related disorders, primarily due to its
contemporary work settings. Safeguarding the health of youngsters employed in
this new, growing economy becomes an occupational health challenge to public
health specialists.
PMID- 25136160
TI - Mobile-health approach: a critical look on its capacity to augment health system
of developing countries.
AB - BACKGROUND: The mobile-health approach is currently knocking the doors of public
health to make use of this rapidly advancing technology in developing countries;
therefore, it needs a critical look on its capacity in improving health system of
developing countries. MATERIALS AND METHODS: A systematic review of studies in
literature published till 31(st) October 2013 of last 10 years on key search
word: Capacity of mobile-health in improving health system of developing
countries was done from medical search engines abstracting databases such as Pub
med, WHO, Cochrane database, Google scholar, and Bio-med Central. Both types of
studies elucidating utility and no benefit of mobile-health in developing
countries were included as main criteria for deciding the capacity of mobile
health approach in health system of developing countries. M-health studies on
areas of impact, effectiveness, and evaluation and previous reviews, conferences
data, and exploratory studies were the main study designs incorporated. Studies
on m-health in developed world, Indian studies as well data from thesis or
dissertation were excluded in this review. DISCUSSION: Multi-faceted mobile
health applications, strategies, and approaches currently lack proper regulation
and standardization from health care authorities, and currently their results
also vary from good to no beneficial effects as found in this review. CONCLUSION:
Umbrella of mobile-health approaches must be used intelligently, keeping in mind
the fact that, it can provide a greater access and quality health care to larger
segments of a rural population and its potential to improve the capacity of
health system in developing countries.
PMID- 25136161
TI - Trends of transfusion transmissible diseases among blood donors at uttarakhand,
India.
AB - CONTEXT: Blood can save lives; however, it can be a source of transfusion
transmitted diseases if proper screening of donated blood is not done. It is now
mandatory to screen all donated blood units, whether replacement or voluntary for
five transfusion transmitted diseases-namely human immunodeficiency virus (HIV),
hepatitis B and C, syphilis, and malaria. AIMS: The present study was done to
study the prevalence of infectious disease markers among donors at the blood bank
of a tertiary care center. SETTINGS AND DESIGN: A total of 53,069 donors donated
blood over 11 years. The number of replacement and voluntary donors was 41,710
and 11,359, respectively. MATERIALS AND METHODS: Screening of blood units was
done by enzyme-linked immunosorbent assay (ELISA) method for HIV and hepatitis B
and C. HIV testing was done using fourth generation ELISA kits. Syphilis was
tested by latex agglutination assay and malaria was tested using slide method up
to the year 2008-2009 and by rapid immunochromatographic assay after that.
RESULTS: The mean percentage of these infections per year was found to be 0.2,
1.2, 0.9, 0.3, and 0.002% for HIV, hepatitis B surface antigen (HBsAg), hepatitis
C virus (HCV), syphilis, and malarial parasite (MP), respectively. CONCLUSIONS:
The risk of transfusion transmissible infection (TTI) today is low but supply of
safe blood depends on proper donor selection and sensitive screening tests.
PMID- 25136163
TI - Tobacco Addiction Among Dental Students: A Reality to be Addressed.
PMID- 25136162
TI - Anemia in elderly: the need to combat the problem.
PMID- 25136164
TI - Metabolic syndrome in the rural population of wardha, central India: confounding
of factor analysis as result of high correlated variables.
PMID- 25136165
TI - Thinking beyond the thomson reuters "impact factor".
PMID- 25136166
TI - Fertility sparing surgery in gynecologic cancer.
AB - Fertility preservation is one of the major concerns of young patients diagnosed
with gynecological cancer. With newer treatment regimens and better surgical
techniques, survival rates after cancer treatment have improved, hence
preservation of fertility has recently become an important issue in the treatment
of gynecological cancers. Fertility sparing surgery may be an option for early
stage cervical cancer with the development of loop excision techniques and
radical trachelectomy which allows a radical approach to cervix cancer at the
same time preserving the uterus and thus fertility. Fertility preservation is
possible in Stage 1 epithelial ovarian cancers, germ cell ovarian tumors, and
borderline cancers. Hormonal therapy with progestin agents is effective in early
endometrial cancer. In patients desiring future pregnancy, fertility sparing
options must be explored before starting treatment for gynecologic cancers.
PMID- 25136167
TI - The never ending debate single-layer versus double-layer closure of the uterine
incision at cesarean section.
PMID- 25136168
TI - Impact of structured counseling on the selection of hormonal contraceptive
methods: results of a multi-centric, observational study in India.
AB - OBJECTIVE: To determine the influence of "structured contraception counseling" on
Indian women's selection of contraceptive methods. METHODS: Women (>=18 and <=40
years) requesting contraception were enrolled at 36 sites. "Structured
contraception counseling" was provided by a health care professional on the
available contraceptive methods. Questionnaires on the women's pre- and post
counseling contraceptive choice, her perceptions, and the reasons behind her post
counseling decision were filled. RESULTS: Significant reductions were observed in
the proportion of women who were indecisive (n = 260; 31.5 % pre-counseling vs. n
= 30; 3.6 %, post-counseling [P < 0.001]) and women opting for non-hormonal
method (24.6 % pre-counseling vs. 6.8 % post-counseling, [P < 0.001]). Of all the
women counseled (n = 825), 89.6 % (739/825) of women chose a hormonal
contraceptive method. There were significant difference (P < 0.001) in the
women's choice of contraceptive in the pre- and post-counseling sessions,
respectively (combined oral contraceptive: 30.8 vs. 40.7 %; vaginal ring: 1.8 vs.
14.1 %; progestogen only pills: 1.6 vs. 7.9 %; injectable-depot
medroxyprogesterone acetate: 5.9 vs. 13.6 %; levonorgestrel-intrauterine system:
3.8 vs. 13.3 %). CONCLUSIONS: Structured contraception counseling using
standardized protocol and aids resulted in a significant increase in the
selection of modern contraceptive methods. Post-counseling majority of women
opted for hormonal methods with an increase in selection of pills and newer
alternatives.
PMID- 25136169
TI - Trends in cesarean delivery: rate and indications.
AB - OBJECTIVES: To compare the cesarean delivery rates over the last decade and to
examine the indications contributing to changed trends, if any. METHODS: To
compare the rate and indications of cesarean delivery over the last decade, the
data were collected in a retrospective manner from all the deliveries that
occurred between January 1 and December 31 in 2001, 2006, and 2011, in the
department of obstetrics and gynecology, Seth G.S. Medical College and K.E.M.
Hospital, a large tertiary care municipal hospital in Western India. A cohort of
20853 delivered women was studied. The rates and indications of primary and
repeat cesarean sections were analyzed among the live births to estimate the
relative contribution of each indication to the overall increase in rate.
RESULTS: The cesarean delivery rate increased from 171.70 to 289.30 per 1,000
live births, with an increase in primary cesarean delivery rate from 118.53
(69.03 %) in 2001 to 210.09 (72.62 %) in 2011 per 1,000 live births. Fetal
distress, arrest of descent, multiple gestations, and fetal indications
contributed to this increase. CONCLUSIONS: There is a significant increase in the
total cesarean rate with primary cesarean accounting for most of the increase.
PMID- 25136170
TI - An analysis of pregnancy outcome in dichorionic and monochorionic twins given
special antenatal and intranatal care: a four-year survey.
AB - OBJECTIVE: The present study aims to analyze perinatal outcomes in twins given
special care during pregnancy and labor and to compare fetal and neonatal
outcomes in dichorionic twins with monochorionic twins. STUDY DESIGN: Eighty
eight (88) twin pregnancies booked for care at a tertiary care Fetal Medicine
centre were included in this study. The maternal demographic variables, course of
pregnancy, fetal problems, and specialized fetal therapeutic and diagnostic
interventions were noted. The above parameters were compared in the sub-groups of
dichorionic and monochorionic twin pregnancies and related to the perinatal
outcome. Statistical analysis was done using the student's t test and the two
tailed chi sqaure tests with Yate's continuity correction. A p value <0.05 was
considered as significant. RESULTS: Mean maternal age was 30.34 + 4.81 years
(range 19-48). 81 % of the twins were DCDA, and 19 % were MCDA. The mean
gestational age at delivery was 34.4 +/- 3.5 weeks, and this was not
significantly different in MCDA and DCDA groups. Serious fetal problems
warranting intervention at the time of initial referral were significantly higher
in MCDA twins although overall perinatal outcome in both groups were not
different. CONCLUSION: Specialized care during pregnancy and labor including
active fetal surveillance and therapeutic intervention when indicated improves
the perinatal outcome in twin pregnancies and ensured at least one healthy live
birth in over 90 % cases, although with an increase in late prematurity.
PMID- 25136171
TI - An observational study of various predictors of success of vaginal delivery
following a previous cesarean section.
AB - OBJECTIVES: To study the various predictors of success for vaginal birth after
cesarean (VBAC) and to study the maternal and fetal outcomes in them and their
comparison with control group. METHODS: This prospective observational study
included 100 women with previous cesarean section in the study group and 100
primigravidas in the control group. Various predictors for success of VBAC were
analyzed and maternal and fetal outcomes were compared with the control group
using student t test, Pearson chi (2) test, and Mann-Whitney U test. RESULTS: Of
100 women with prior cesarean Sect. 65 had successful trial of labor, while 35
underwent a repeat cesarean section. Maternal complications in the previous CS
group were 15 % as compared to only 2 % in the control group (p < 0.001).
CONCLUSION: Maternal pre-pregnancy BMI, non-recurring indications of previous
cesarean section, good Bishop's score at the time of admission, spontaneous onset
of labor, and neonatal birth weight were significantly related to high chances of
success of vaginal birth after previous cesarean section. Maternal complications
were more common in study group, but the fetal outcomes were similar.
PMID- 25136172
TI - The outcome of septic abortion: a tertiary care hospital experience.
AB - OBJECTIVE: To study the incidence of septic abortion, reasons for that,
sociodemographic profile, abortion providers, complications faced, and treatment
given and its outcome. METHODS: All the women with septic abortion admitted at
Government Maternity Hospital, Tirupathi, over a period of 2 years 4 months
duration from July 2007 to October 2009 were studied prospectively. OBSERVATIONS
AND RESULTS: Incidence of septic abortion in our study was 6.78 %. 72 % of cases
were performed by qualified medical personnel. Fourteen patients had
complications, among them peritonitis, pelvic abscess, renal failure, and septic
shock were common. Twenty-six patients had Grade-I sepsis, Grade-II: 8, Grade
III: 4, and Grade-IV: 4. Laparotomy was done in six cases. There was no mortality
in our study. CONCLUSION: The tragedy of septic-induced abortion is totally
preventable. It only needs definitive commitment to women's health by providing
effective contraception, strengthening the family welfare services, and
discouraging repeated terminations of pregnancy as contraceptive method.
PMID- 25136173
TI - Labor Induction with 50 MUg Vaginal Misoprostol: Can We Reduce Induction-Delivery
Intervals Safely?
AB - OBJECTIVE: To compare the efficacy and safety profile of two methods of labor
induction i.e., intracervical dinoprostone gel (0.5 mg 8 h) and misoprostol (50
MUg 4 h) for induction of labor in women with a poor Bishop's score. DESIGN:
Observational study. STUDY PERIOD: January 1st, 2009 to December 31st, 2010.
POPULATION: A total of 329 women with unfavorable cervices induced at or near
term. METHODS: Two cervical ripening agent study arms were used: dinoprostone gel
(193 women) and misoprostol (137 women). MAIN OUTCOME MEASURES: Induction to
delivery interval, cesarean section, incidence of meconium stained liquor, FHR
pattern, incidence of uterine hyperstimulation, and neonatal outcomes. RESULTS:
The induction to delivery interval was significantly shorter in the misoprostol
group as compared to the dinoprostone group (p < 0.001). There was no difference
in cesarean section rates between the two groups (dinoprostone gel 43 %;
misoprostol 33 %; p = 0.144). The incidence of non-reassuring fetal heart rate
pattern, meconium stained liquor, and uterine hyperstimulation were equivalent in
both the groups (p = 0.529; 0.733; and 0.321, respectively). The neonatal
outcomes in both the groups were comparable in terms of Apgar scores at birth (p
= 0.160) and NICU admissions (p = 0.951). CONCLUSIONS: Labor induction in women
with unfavorable cervices results in high caesarean section rates. However, the
use of misoprostol significantly reduces the induction to delivery interval,
without adversely affecting the caesarean section rates and neonatal outcomes.
Hence it may become a cost-effective alternative to dinoprostone gel in resource
poor settings like India.
PMID- 25136174
TI - Urogenital infections as a risk factor for preterm labor: a hospital-based case
control study.
AB - PURPOSE: Preterm labor is a leading cause of neonatal morbidity and mortality.
Ascending lower genital tract infection leads to preterm labor and adverse
pregnancy outcomes. This prospective case-control study was performed to see the
association between preterm labor and urogenital infections. METHODS: A total of
104 women were observed for urogenital infections and their association with
preterm labor. Case Group I included 52 women with preterm labor after 26 weeks
and before 37 completed weeks of gestation with or without rupture of membranes.
Control Group II included 52 women at completed or more than 37 weeks of
gestation with no history of preterm labor, matched to the case group with
respect to age and parity. Midstream urine was sent for cytology and culture
sensitivity. Samples from posterior fornix of vagina were taken with two
sterilized swabs under direct vision using Cusco/Sims speculum before first
vaginal examination and were studied for gram stain characteristics and culture
sensitivity by standard methods. Microorganisms isolated on culture were noted,
and antibiotics were given according to sensitivity. Data collected were analyzed
according to the groups by chi(2) test for categorical variables. RESULTS: In our
study, urogenital infection was seen in 19 women in Case Group I (36.54 %)
compared with 9 women in Control Group (17.3 %), and the difference was
statistically significant (p 0.027). CONCLUSION: Recognizing and treating the
women having urogenital infections at a stage, when it has not become clinically
evident, will decrease the percentage of women going into preterm labor and will
improve the perinatal outcome.
PMID- 25136175
TI - Prevalence and clinical utility of human papilloma virus genotyping in patients
with cervical lesions.
AB - OBJECTIVE: Cervical cancer is the commonest cancer among Indian women. High-risk
human papilloma virus (HPV) detection holds the potential to be used as a tool to
identify women, at risk of subsequent development of cervical cancer. There is a
pressing need to identify prevalence of asymptomatic cervical HPV infection in
local population. In our study, we explored the prevalence of HPV genotypes and
their distribution in women with cervical lesions. METHODS: Scrape specimens were
obtained from 100 women (study group) with cervical abnormalities. HPV was
detected with amplicor HPV tests, and the individual genotypes in these specimens
were identified by Hybribio Genoarray test kit. Fifty specimens were also
collected from females with healthy cervix (control group). The present study
also aimed to determine the status of HPV prevalence and its association with
different sociodemographic factors. RESULTS: Out of the total number of 100
samples, 10 (10 %) women tested positive for HPV DNA. Among them, HPV 18 was
observed in 6, HPV 16 in 2, HPV 52 and HPV 39 in one each. Fifty specimens
collected from patients with healthy cervix were not infected with any of the HPV
genotype. CONCLUSIONS: Our study generates data of HPV prevalence in patients
with cervical lesions visiting tertiary care institute. The data generated will
be useful for laying guidelines for mass screening of HPV detection, treatment,
and prophylaxis.
PMID- 25136176
TI - Correlation of Cytology and Colposcopic Findings Using Reid's Index in VIA
Positive Women.
AB - INTRODUCTION: Cervical cancer is the most common cancer among Indian women. Only
5 % of women in developing countries have ever been screened for cervical
abnormalities. OBJECTIVES: To study the correlation of cytology and colposcopy in
VIA-positive women attending the Gynaecology clinic. MATERIALS AND METHODS: This
prospective cross-sectional study on 200 symptomatic women compares the role of
cytology and colposcopy in the assessment of subjects testing positive for
acetowhite lesions on the cervix after application of 5 % acetic acid (VIA).
RESULTS: 200/637 women screened in OPD tested VIA positive, giving a positivity
rate of 31 %. Six smears were reported as LGSIL or HGSIL giving a cytological
abnormality rate of 3 %. The association between cytology and Reid's score was
statistically significant at a p value of 0.02. Of the 4 cases with biopsy
confirmed invasive cancer, cytology reported 2 as LGSIL and 2 as HGSIL.
Colposcopy reported all these women as CIN 2/3. CONCLUSION: The accuracies of Pap
smear cytology and colposcopy in the diagnosis of precancerous and cancerous
lesions of cervix were good.
PMID- 25136177
TI - Conservative management of interstitial pregnancy.
PMID- 25136178
TI - Severe hemolytic disease of newborn in a rh d-positive mother: time to mandate
the antenatal antibody screening.
PMID- 25136179
TI - Residual adherent placenta with bladder injury: can we use methotrexate?
PMID- 25136180
TI - A rare case of criminal abortion with retained foreign body in uterus for 2
years.
PMID- 25136181
TI - Successful Pregnancy with Endometrial Stromal Sarcoma (ESS).
PMID- 25136183
TI - Office Hysteroscopy: TROPHYscope CAMPO Compact Hysteroscope ((r)): Manufacturer:
KARL STORZ, Tuttlingen, Germany.
PMID- 25136182
TI - Diagnosing GDM: Role of Simple, Cost Effective, and Sensitive DIPSI Test.
PMID- 25136184
TI - Scrub typhus: Emerging cause of multiorgan dysfunction.
PMID- 25136185
TI - Noninvasive ventilation success: Combining knowledge and experience.
PMID- 25136186
TI - Optimum positive end-expiratory pressure 40 years later.
PMID- 25136187
TI - Profile of organ dysfunction and predictors of mortality in severe scrub typhus
infection requiring intensive care admission.
AB - BACKGROUND AND AIMS: Scrub typhus, a zoonotic rickettsial infection, is an
important reason for intensive care unit (ICU) admission in the Indian
subcontinent. We describe the clinical profile, organ dysfunction, and predictors
of mortality of severe scrub typhus infection. MATERIALS AND METHODS:
Retrospective study of patients admitted with scrub typhus infection to a
tertiary care university affiliated teaching hospital in India during a 21-month
period. RESULTS: The cohort (n = 116) aged 40.0 +/- 15.2 years (mean +/- SD),
presented 8.5 +/- 4.4 days after symptom onset. Common symptoms included fever
(100%), breathlessness (68.5%), and altered mental status (25.5%). Forty-seven
(41.6%) patients had an eschar. Admission APACHE-II score was 19.6 +/- 8.2.
Ninety-one (85.2%) patients had dysfunction of 3 or more organ systems.
Respiratory (96.6%) and hematological (86.2%) dysfunction were frequent.
Mechanical ventilation was required in 102 (87.9%) patients, of whom 14 (12.1%)
were solely managed with non-invasive ventilation. Thirteen patients (11.2%)
required dialysis. Duration of hospital stay was 10.7 +/- 9.7 days. Actual
hospital mortality (24.1%) was less than predicted APACHE-II mortality (36%; 95%
Confidence interval 32-41). APACHE-II score and duration of fever were
independently associated with mortality on logistic regression analysis.
CONCLUSIONS: In this cohort of severe scrub typhus infection with multi-organ
dysfunction, survival was good despite high severity of illness scores. APACHE-II
score and duration of fever independently predicted mortality.
PMID- 25136188
TI - Noninvasive ventilation: Are we overdoing it?
AB - BACKGROUND: Use of noninvasive ventilation (NIV) outside guideline
recommendations is common. We audited use of NIV in our tertiary care critical
care unit (CCU) to evaluate appropriateness of use and patient outcomes when used
outside level I recommendations. MATERIALS AND METHODS: Prospective observational
study of all patients requiring NIV. Clinical parameters and arterial blood gases
were recorded at initiation of NIV and 2 h later (or earlier if clinically
warranted). NIV titration and decision to intubate were left to the discretion of
treating intensivist. Patients were categorized into two groups: Group 1: Those
with level I indications for use of NIV and group 2: All other levels of
indications. Patients were followed until hospital discharge. RESULTS: From
January 2010 to June 2010, 1120 patients were admitted to the CCU. Of these 106
patients required NIV support with 40.6% (n = 43/106) being in group 1 and 59.4%
(n = 63/106) in group 2. Of these 35.8% patients (38/106) failed NIV and required
endotracheal intubation. NIV failure rates (41.27% vs. 27.91%; P = 0.02) and
mortality (30.6% vs. 18.6%; P = 0.03) were significantly higher in group 2
patients. In a logistic regression analysis Acute Physiology and Chronic Health
Evaluation (APACHE) II score (P = 0.02), time on NIV before intubation (P =
0.001) and baseline PaCO2 levels (P = 0.01) were strongly associated with
mortality. CONCLUSION: Noninvasive ventilation failure and mortality rates were
significantly higher when used outside level I recommendations. APACHE II score,
baseline PaCO2 and duration on NIV prior to intubation were predictors of
increased mortality.
PMID- 25136189
TI - Compliance versus dead space for optimum positive end expiratory pressure
determination in acute respiratory distress syndrome.
AB - OBJECTIVE: To Compare compliance versus dead space (Vd) targeted positive end
expiratory pressure (PEEP) as regard its effect on lung mechanics and
oxygenation. MATERIALS AND METHODS: This study was carried out on 30 adult acute
respiratory distress syndrome patients. The ventilator was initially set on
volume controlled with tidal volume (Vt) 7 mL/kg predicted body weight (PBW),
inspiratory plateau pressure (Ppl) <30 cm H2 O. If the Ppl was >30 cm H2 O with a
TV of 6 mL/kg PBW, a step-wise Vt reduction of 1 mL/kg PBW to as low as 4
mL/kg/PBW was allowed. Respiratory rate adjusted to maintain pH 7.30-7.45. FiO2
start at 100%. Best PEEP determined at 2 points, one by titrating PEEP until
reaching the highest static compliance (Cst) (PEEP Cst) and the other one is at
the lowest Vd/Vt (PEEP Vd/Vt). The following data measured before and 30 min
after setting PEEP Cst and PEEP Vd/Vt. Cst, PaCO2 - PetCO2, Vd/Vt, PaO2 /FiO2,
Ppl, heart rate, mean arterial pressure and oxygen saturation. RESULTS: optimum
PEEP determined by Vd/Vt was significantly (P < 0.05) lower than the optimum PEEP
determined by Cst. Best PEEP Vd/Vt showed a significant decrease (P < 0.05) in
Cst, PaCO2 - PetCO2, Vd/Vt and Ppl in comparison with best PEEP Cst. The PaO2
/FiO2 showed a significant increase (P < 0.05) with best PEEP Vd/Vt in comparison
with best PEEP Cst. CONCLUSION: Vd guided PEEP improved compliance and
oxygenation with less Ppl. Hence, its use as a guide for best PEEP determination
may be useful.
PMID- 25136190
TI - Funding sources for continuing medical education: An observational study.
AB - AIMS: Medical accreditation bodies and licensing authorities are increasingly
mandating continuing medical education (CME) credits for maintenance of licensure
of healthcare providers. However, the costs involved in participating in these
CME activities are often substantial and may be a major deterrent in obtaining
these mandatory credits. It is assumed that healthcare providers often obtain
sponsorship from their institutions or third party payers (i.e. pharmaceutical
industry) to attend these educational activities. Data currently does not exist
exploring the funding sources for CME activities in India. In this study, we
examine the relative proportion of CME activities sponsored by self, institution
and the pharmaceutical-industry. We also wanted to explore the characteristics of
courses that have a high proportion of self-sponsorship. MATERIALS AND METHODS:
This is a retrospective audit of the data during the year 2009 conducted at an
autonomous clinical training academy. The details of the sponsor of each CME
activity were collected from an existing database. Participants were subsequently
categorized as sponsored by self, sponsored by institution or sponsored by
pharmaceutical-industry. RESULTS: In the year 2009, a total of 2235 participants
attended 40 different CME activities at the training academy. Of the total
participants, 881 (39.4%) were sponsored by self, 898 (40.2%) were sponsored by
institution and 456 (20.3%) by pharmaceutical-industry. About 47.8% participants
attended courses that carried an international accreditation. For the courses
that offer international accreditation, 63.3% were sponsored by self, 34.9% were
sponsored by institution and 1.6% were sponsored by pharmaceutical-industry.
There were 126 participants (5.6%) who returned to the academy for another CME
activity during the study period. Self-sponsored (SS) candidates were more likely
to sponsor themselves again for subsequent CME activity compared with the other
two groups (P < 0.001). CONCLUSIONS: In our study, majority of healthcare
professionals attending CME activities were either self or institution sponsored.
There was a greater inclination for self-sponsoring for activities with
international accreditation. SS candidates were more likely to sponsor themselves
again for subsequent CME activities.
PMID- 25136193
TI - Successful use of sustained low efficiency dialysis in a case of severe
phenobarbital poisoning.
AB - A 30-year-old female presented with coma and subsequent cardiac arrest caused by
phenobarbital overdosage, requiring ventilatory and vasopressor support. She had
also developed severe hypoxia following gastric aspiration. Initial therapy,
including activated charcoal and forced alkaline diuresis, failed to
significantly lower her drug levels and there was minimal neurological
improvement. As she was hemodynamically unstable, and unsuitable for conventional
dialysis, she was put on sustained low efficiency dialysis (SLED) to facilitate
drug removal. SLED resulted in marked reduction in plasma level of phenobarbital,
which eventually led to early extubation, improved cognition and aided full
recovery. Thus, we concluded that SLED can be an effective alternative in cases
of severe phenobarbital poisoning, where conventional hemodialysis or
hemoperfusion cannot be initiated, to hasten drug elimination and facilitate
early recovery.
PMID- 25136192
TI - Hyperkalemic paralysis in primary adrenal insufficiency.
AB - Hyperkalemic paralysis due to Addison's disease is rare, and potentially life
threatening entity presenting with flaccid motor weakness. This case under
discussion highlights Hyperkalemic paralysis as initial symptomatic manifestation
of primary adrenal insufficiency.
PMID- 25136194
TI - An unusual cause of gastrointestinal bleed.
AB - Gastrointestinal (GI) bleed often brings the patient to the emergency medical
service with great anxiety. Known common causes of GI bleed include ulcers,
varices, Mallory-Weiss among others. All causes of GI bleed should be considered
however unusual during the evaluation. Aortoenteric fistula (AEF) is one of the
unusual causes of GI bleed, which has to be considered especially in patients
with a history of abdominal surgery in general and aortic surgery in particular.
PMID- 25136191
TI - Pediatric acute kidney injury: A syndrome under paradigm shift.
AB - The recent standardization and validation of definitions of pediatric acute
kidney injury (pAKI) has ignited new dimensions of pAKI epidemiology and its risk
factors. pAKI causes increased morbidity and mortality in critically ill
children. Among the hospitalized patients incidence of pAKI ranges from 1% to
31%, while mortality ranges from 28% to 82%, presenting a broad range due to lack
of uniformly acceptable pAKI definition. In addition, cumulative data regarding
the progression of pAKI to chronic kidney disease in children is rising. Despite
these alarming figures, treatment modalities have failed to deliver
significantly. In this review, we will summarize the latest developments of pAKI
and highlight important aspects of pAKI management.
PMID- 25136195
TI - Spontaneous cryptococcal peritonitis with fungemia in patients with decompensated
cirrhosis: Report of two cases.
AB - Cryptococcus neoformans is encapsulated yeast that predominately infects
immunocompromised individuals. Liver disease is an under-recognized
predisposition for cryptococcal disease. We report two nonalcoholic, nondiabetic,
and human immunodeficiency virus - negative cirrhotic patients, with spontaneous
cryptococcal peritonitis. Cryptococcus infection was diagnosed by culture of
ascitic fluid and peripheral blood in both. We treated the first patient with
amphotericin-B, but he expired. The second patient with earlier diagnosis,
survived to discharge with fluconazole treatment. We suggest a high clinical
suspicion for Cryptococcus as a possible etiology of spontaneous peritonitis in
cirrhotic patients.
PMID- 25136196
TI - Deep vein thrombosis of upper extremities due to reactive thrombocytosis in
septic patients.
AB - Deep venous thrombosis (DVT) is not an uncommon condition in the intensive care
unit (ICU), and having high morbidity and mortality. Upper limb DVT also is
increasingly being recognized as a clinical entity. The presence of the
indwelling catheter in neck veins is a risk for developing venous thrombus, which
may be further aggravated by presence of thrombocytosis. In ICU patients with
sepsis, reactive thrombocytosis has been found during the recovery phase. Here,
we are presenting two cases, having thrombocytosis and central venous catheter
who developed upper limb DVT.
PMID- 25136197
TI - Multinodular goiter with retrosternal extension causing airway obstruction:
Management in intensive care unit and operating room.
PMID- 25136198
TI - Management of snake bite victims in a Tertiary Care Intensive Care Unit in North
India.
PMID- 25136199
TI - Ofloxacin-induced toxic epidermal necrolysis.
PMID- 25136200
TI - Internal jugular vein thrombosis from rhino-cerebral mucormycosis: Be careful
before cannulation.
PMID- 25136201
TI - Vasovagal syncope during spirometric exercise.
PMID- 25136202
TI - Acute epiglottitis from corrosive ingestion.
PMID- 25136203
TI - Application of rapid ultrasound in shock protocol in the ICU for management of
shock.
PMID- 25136205
TI - The dynamics and power of change: changing practices in cutaneous and aesthetic
surgery.
PMID- 25136207
TI - Management of infantile hemangiomas.
PMID- 25136206
TI - Management of infantile hemangiomas: current trends.
AB - Infantile hemangiomas (IH) are common vascular tumours. IH have a characteristic
natural course. They proliferate rapidly during the early infantile period
followed by a period of gradual regression over several years. Most of the
uncomplicated IH undergo spontaneous involution, with a small proportion of cases
requiring intervention. These are children with IH in life-threatening locations,
local complications like haemorrhage, ulceration and necrosis and functional or
cosmetic disfigurements. Systemic corticosteroids have been the first line of
treatment for many years. Recently, non-selective beta-blockers, such as oral
propranalol and topical timolol, have emerged as promising and safer therapies.
Other treatment options include interferon alpha and vincristine which are
reserved for life-threatening haemangiomas that are unresponsive to conventional
therapy. This review mainly focuses on the current trends and evidence-based
approach in the management of IH.
PMID- 25136208
TI - Fractional CO2 Laser Resurfacing as Monotherapy in the Treatment of Atrophic
Facial Acne Scars.
AB - BACKGROUND: While laser resurfacing remains the most effective treatment option
for atrophic acne scars, the high incidence of post-treatment adverse effects
limits its use. Fractional laser photothermolysis attempts to overcome these
limitations of laser resurfacing by creating microscopic zones of injury to the
dermis with skip areas in between. AIM: The aim of the present study is to assess
the efficacy and safety of fractional CO2 laser resurfacing in atrophic facial
acne scars. MATERIALS AND METHODS: Sixty patients with moderate to severe
atrophic facial acne scars were treated with 3-4 sessions of fractional CO2 laser
resurfacing at 6-week intervals. The therapeutic response to treatment was
assessed at each follow up visit and then finally 6 months after the last laser
session using a quartile grading scale. Response to treatment was labelled as
'excellent' if there was >50% improvement in scar appearance and texture of skin
on the grading scale while 25-50% response and <25% improvement were labelled as
'good' and 'poor' response, respectively. The overall satisfaction of the
patients and any adverse reactions to the treatment were also noted. RESULTS:
Most of the patients showed a combination of different morphological types of
acne scars. At the time of final assessment 6 months after the last laser
session, an excellent response was observed in 26 patients (43.3%) while 15 (25%)
and 19 patients (31.7%) demonstrated a good and poor response respectively.
Rolling and superficial boxcar scars responded the best while pitted scars
responded the least to fractional laser monotherapy. The commonest reported
adverse effect was transient erythema and crusting lasting for an average of 3-4
and 4-6 days, respectively while three patients developed post-inflammatory
pigmentation lasting for 8-12 weeks. CONCLUSIONS: Fractional laser resurfacing as
monotherapy is effective in treating acne scars especially rolling and
superficial boxcar scars with minimal adverse effects.
PMID- 25136210
TI - Efficacy of triple therapy in auricular keloids.
AB - BACKGROUND: Keloids are characterised by their continued growth following trauma,
extension into normal tissue and their high recurrence rate following excision.
Auricular keloids are common following ear piercing or flame burns. These lesions
are highly conspicuous and cosmetically unappealing. Multiple methods including
surgery, radiotherapy, antimitotic agents, silicone sheet, pressure clips and
cryotherapy have been advocated. The risk of recurrence and the need to prevent
distortion of the three-dimensional structure of the ear following resection is a
challenge to the cutaneous surgeon. OBJECTIVES: To devise a standard protocol for
management of auricular keloids with minimal distortion and recurrence. SETTING
AND DESIGN: The patients underwent day-care surgery and subsequent out-patient
follow-up for a minimum period of 1 year. METHODS: Ten patients presenting with
22 ear keloids were enrolled into a keloid protocol: (a) surgical excision and
keloid rind flap cover with (b) intra-operative and post-operative intra-lesional
steroid and (c) silicone sheet application. Subjective assessment on follow-up
was using Patient Observer Scar Assessment Scale and objective assessment was by
Beausang scale. STATISTICAL ANALYSIS USED: Microsoft Excel and Statistical
Package for the Social Sciences (SPSS). Kaplan-Meier survival analysis curve used
to calculate Recurrence Free period. RESULTS: Two out of 22 (9.1%) keloids
developed post-excision recurrence after a mean follow -up period of 16 months.
The average keloid recurrence free interval was 21 months. CONCLUSION: Triple
combination therapy for keloids on the ear is a simple technique for management
with preservation of contour of the ear and a low recurrence rate.
PMID- 25136209
TI - Evaluation of microneedling fractional radiofrequency device for treatment of
acne scars.
AB - BACKGROUND: Various treatment modalities including non-invasive methods such as
chemical peels, topical retinoids, microdermabrasion, minimally invasive
techniques such as microneedling, fractional lasers, microneedling radiofrequency
devices and invasive procedures such as acne scar surgeries and ablative lasers
are used for acne scars, each with its own unique advantages and disadvantages.
This study is a retrospective assessment of efficacy and safety of microneedling
fractional radiofrequency in the treatment of acne scars. METHODS: Thirty one
patients of skin types III-V with moderate and severe facial acne scarring
received four sequential fractional radiofrequency treatments over a period of 6
months with an interval of 6 weeks between each session. Goodman & Baron's acne
scar grading system was used for assessment by a side by side comparison of
preoperative and post- operative photographs taken at their first visit and at
the end of 3 months after the last session. RESULTS: Estimation of improvement
with Goodman and Baron's Global Acne Scarring System showed that by qualitative
assessment of 31 patients with grade 3 and grade 4 acne scars, 80.64% showed
improvement by 2 grades and 19.35% showed improvement by 1 grade. Quantitative
assessment showed that 58% of the patients had moderate, 29% had minimal, 9% had
good and 3% showed very good improvement. Adverse effects were limited to
transient pain, erythema, edema and hyperpigmentation. CONCLUSION: Microneedling
fractional radiofrequency is efficacious for the treatment of moderate and severe
acne scars.
PMID- 25136211
TI - Outcomes of staple closure of the donor area during hair transplant by follicular
unit transfer.
AB - BACKGROUND: Donor area closure in hair transplantation by follicular unit
transfer (FUT) is being done by various techniques. This study aims to assess the
outcomes of staple closure for donor area in FUT. AIM: To study the outcome,
efficacy and complications of staples in donor area closure for FUT. MATERIALS
AND METHODS: A total of 50 consecutive patients who underwent staple closure for
donor area in FUT were included in the study and their data were collected
retrospectively. Patients were followed up one year after the surgery and
photographic documentation of the scar at the donor site was done. Objective
measurement of the width of the scar was done for all the patients. RESULTS: The
average length of the donor area was 22 cm. The average width of the scar was
1.82 mm. There was no infection or tissue necrosis at the staple closure site in
any of the patients. CONCLUSION: Staple closure resulted in cosmetically
acceptable scar, but post operative discomfort was the major limitation. The
potential to conserve the hair follicles along the line of closure makes using
staples worthwhile if conservation of follicles is the goal.
PMID- 25136212
TI - Platelet-rich plasma in androgenic alopecia: myth or an effective tool.
AB - Platelet-rich plasma (PRP) has become a newer method for the treatment of various
types of alopecia. In this prospective study, safety, efficacy and feasibility of
PRP injections in treating androgenic alopecia were assessed. Eleven patients
suffering from hair loss due to androgenic alopecia and not responding to 6
months treatment with minoxidil and finasteride were included in this study. The
hair pull test was performed before every treatment session. A total volume of 2
3 cc PRP was injected in the scalp by using an insulin syringe. The treatment was
repeated every two weeks, for a total of four times. The outcome was assessed
after 3 months by clinical examination, macroscopic photos, hair pull test and
patient's overall satisfaction. RESULTS: A significant reduction in hair loss was
observed between first and fourth injection. Hair count increased from average
number of 71 hair follicular units to 93 hair follicular units. Therefore,
average mean gain is 22.09 follicular units per cm(2.) After the fourth session,
the pull test was negative in 9 patients. CONCLUSION: PRP injection is a simple,
cost effective and feasible treatment option for androgenic alopecia, with high
overall patient satisfaction.
PMID- 25136213
TI - Platelet Rich Plasma in Androgenic Alopecia: Where do we Stand?
PMID- 25136215
TI - Gynaecomastia Surgery: Should it be Individualised?
PMID- 25136214
TI - Role of Combined Circumareolar Skin Excision and Liposuction in Management of
High grade Gynaecomastia.
AB - INTRODUCTION: High-grade gynaecomastia (Simon IIb and III) has tissue excess
(skin excess, enlarged areola, and displaced nipple), which is best managed
surgically; however, results of conventional breast reduction surgeries and
liposuction is not very good. Aim of our study was to describe a combined
technique to manage these problems to produce a good result. MATERIAL AND METHOD:
This was a 2-year study among 12 patients of high grade gynaecomastia. Clinical
and laboratory findings were normal. Pre-operatively in standing position,
diameter of breast and areola, position of nipple, and amount of skin excess were
marked. Under general anaesthesia, tumescent infiltration, circumareolar de
epithelisation of skin excess, and liposuction was completed. Redundant portion
of the breast was sharply dissected and pulled out. Areola was fixed over
pectoralis fascia at mid humerus level, just medial to the mid-clavicular line.
Outer borders of the de-epithelised area were apposed by the purse-string effect
of a subdermal suture, and further apposed by few half buried horizontal mattress
sutures. Drains for 24 hour and compressive dressings for 6 weeks were used.
RESULT: Mean age of presentation was 25.8 year; emotional discomfort was the
chief complaint. Among 12 patients, 10 patients had bilateral gynaecomastia and 8
patients had enlarged and displaced nipple-areola complex. Average hospital stay
was 2.41 days and recoveries were usually uneventful. CONCLUSION: The problem of
tissue excess and tissue displacement in high grade gynaecomastia can be well
managed by this combined circumareolar skin reduction and liposuction technique
to achieve a scar-less flat male chest.
PMID- 25136216
TI - Targeted cryotherapy using disposable biopsy punches.
AB - Cryotherapy is a commonly used office procedure that causes destruction of tissue
by cryonecrosis due to rapid freezing and thawing of cells. The limitation in
treating plantar warts and deeper dermal lesions is that the freeze time should
be longer to penetrate deeper, which results in collateral damage to normal skin
surrounding the lesion. This results in unwanted side effects of prolonged pain,
blistering and haemorrhage and increased healing time. The cone spray technique
was used to reduce collateral damage, but deeper penetration is difficult to
achieve. An innovative technique using disposable biopsy punches is described
that ensures deeper freezing as compared to the plastic cone. The metal cutting
edge of the punch enters deeper into the lesions as the liquid nitrogen is
passed, sparing damage to surrounding skin.
PMID- 25136217
TI - How to practice dermatosurgery safely?
AB - Dermatosurgery has become an integral and essential component of current
dermatology practice. No surgery can be totally risk free, only the level of risk
varies. Patient safety has to be ensured by following standard protocols and
taking appropriate precautions to prevent complications and mishaps. Mismatch
between patient's expectations and outcome can lead to litigation. A
dermatosurgeon should take care of his legal safety by obtaining informed consent
and meticulously documenting and preserving medical records. Importance of
communication and maintaining of fiduciary relationship with the patient cannot
be overemphasized.
PMID- 25136218
TI - Buying a laser - tips and pearls.
AB - Lasers and aesthetic procedures have transformed dermatology practice. They have
aided in the treatment of hitherto untreatable conditions and allowed better
financial remuneration to the physician. The availability of a variety of laser
devices of different makes, specifications and pricing has lead to confusion and
dilemma in the mind of the buying physician. There are presently no guidelines
available for buying a laser. Since purchase of a laser involves large
investments, careful consideration to laser specifications, training, costing,
warranty, availability of spares, and reliability of service are important
prerequisites. This article describes various factors that are needed to be
considered and also attempts to lay down criteria to be assessed while buying a
laser system that will be useful to physicians before investing in a laser
machine. PRACTICE POINTS: Meticulous planning of the type of machine,
specifications, financial aspects, maintenance and warranties is important.It is
wise to sign a contract or agreement between the buyer and seller before purchase
of a laser which covers key aspects of installation, after sales service and
maintenance of the machine.Adequate training is essential; understanding laser
physics and laser-tissue interaction goes a long way in getting the best out of
the machine.The credibility of the dealer and company should be ascertained in
order to be assured of after-sales service.Buying used machines, sharing of
equipment to offset high initial investments is a good option but even more care
is required to ensure proper functioning and maintenance.
PMID- 25136220
TI - Favre-racouchot syndrome with bilateral mechanical ptosis: an unusual
presentation.
PMID- 25136219
TI - Primary Bilateral Extramammary Paget's Disease of the Axillae: Another Case of
this Strange Disease.
AB - Primary extramammary Paget's disease of the axilla is a rare variant with the
capability of mimicking other more common conditions. We present a case of a 65
year-old woman with inflammatory skin lesions of both axillae clinically
unresponsive to long-term conventional topical therapy. We decided to excise and
reconstruct the resulting soft tissue defect of the major lesion by using a
thoraco-dorsal artery perforator-based Limberg's flap. The histopathological
examination showed intracellular mucin, signet cells, and glandular structures,
the typical pattern of the EMPD. This was a very interesting case of a per se
rare condition.
PMID- 25136221
TI - Re: superficial large Basal cell carcinoma over face, reconstructed by v-y
plasty.
PMID- 25136222
TI - Author's reply.
PMID- 25136223
TI - Re: Propranolol for infantile haemangiomas: Early experience from a tertiary
center.
PMID- 25136224
TI - Author's reply.
PMID- 25136225
TI - Reply to expert comments - a study of donor area in follicular unit hair
transplantation.
PMID- 25136226
TI - Cavitary anomalies of the optic disc: Different entities or part of a single
spectrum of disease?
PMID- 25136227
TI - Non-drainage scleral buckling with solid silicone elements.
AB - BACKGROUND: With the increasing number of cataract surgeries, incidence of
posterior segment complications including rhegmatogenous retinal detachment (RRD)
is likely to rise. Scleral buckling (SB) surgery is an effective and less
expensive option. The primary advantage of non-drainage procedure is avoidance of
possible complications associated with trans-choroidal drainage. The aim of
present study is to describe the clinical profile of subjects undergoing non
drainage SB surgery with solid silicone elements for RRD and analyze their
treatment outcomes. MATERIALS AND METHODS: This was a retrospective, non
randomized, interventional study at a tertiary care center. Three hundred and six
eyes of 298 patients undergoing non-drainage SB surgery with solid silicone
elements from year 2000 to 2006 were included. Inclusion criteria were primary
RRD, peripheral depressible retinal break, media clarity affording peripheral
retinal view and proliferative vitreo-retinopathy (PVR) up to grade C2. Uni- and
multivariate analyses was done to analyze factors affecting anatomical and visual
outcomes. Statistical analysis was performed using SPSS Version 10. RESULTS: Mean
follow-up was 303 +/- 393.33 days. Primary anatomical success was obtained in 279
(91.2%) eyes; primary functional success in 286 (93.5%) eyes. PVR (grade B or C),
intraocular pressure <10 mm Hg and the inability to find a retinal break were
significantly associated with final anatomical failure. Baseline vision <=3/60
was significantly associated with poor visual recovery. CONCLUSIONS: SB surgery
is reasonably safe and highly efficacious. Solid silicone elements are effective
in non-drainage SB surgery. However, case selection is important.
PMID- 25136228
TI - Botulinum neurotoxin type A versus punctal plug insertion in the management of
dry eye disease.
AB - PURPOSE: To compare the efficacies of punctal plug insertion and Botulinum toxin
injection in dry eye disease not responding to topical medications. MATERIALS AND
METHODS: A non-controlled randomized clinical trial of two parallel groups of 60
dry eye patients seen in the clinic not responding to topical medications were
divided into two groups. One group received punctal plugs and the other group
received Botulinum toxin injections to prevent lacrimal tear drainage. RESULTS:
Of a total of 36 patients with a mean age of 44.5 years who received punctal
plugs, 50% of them experienced improvements in the clinical manifestations of
their disease. 12/36 (33.3%) developed plug extrusion, and 6/36 (16.7%) patients
developed conjunctival erosions with irritation that necessitated plug removal
within one week of insertion. A total of 24 patients with a mean age of 47.5
years received injections of Botulinum toxin. Of these, 83.3% had improvement in
all of the clinical manifestations of dry eye. 4/24 (16.7%) had no improvement in
the degrees to which they experienced foreign body sensations, 33.3% reported
shampoo entering the eye while showering. All of the patients who received
Botulinum toxin injections were satisfied with the results of their treatment,
whereas only 72.3% of the patients who received punctal plugs were satisfied with
their results. CONCLUSION: Botulinum neurotoxin A injections can be a very good
alternative to punctal plugs in improving the clinical manifestations of dry eye
disease They are associated with the development of fewer and milder
complications and with higher levels of patient satisfaction.
PMID- 25136229
TI - Ancient schwannoma of the orbit.
AB - The ancient schwannoma is a rare variant of a neurilemoma with a course typical
of a slow-growing benign neoplasm. Histologically, it can be confused with a
malignant mesenchymal tumor because of increased cellularity, nuclear
pleomorphism, and hyperchromatism. Despite the degree of nuclear atypia, mitotic
figures are absent. We describe the clinical and histopathologic features of an
ancient schwannoma of the orbit. A need for early removal of such tumors is
recommended to prevent complications.
PMID- 25136230
TI - Cornelia de Lange syndrome with optic disk pit: Novel association and review of
literature.
AB - Cornelia de Lange syndrome (CdLS), also called Brachmann-de Lange syndrome, is a
multiple congenital anomaly syndrome characterized by a distinctive facial
appearance, ophthalmological abnormalities, prenatal and postnatal growth
deficiency, psychomotor delay, behavioral problems, and malformations of the
upper extremities. Most common and consistent ophthalmic features reported are
nasolacrimal duct obstruction, long and curly eyelashes, blepharitis, ptosis,
synophrys, telecanthus, hypertelorism, microcornea, peripapillary pigment ring,
and myopia. In this report we report a case of a 5-year old boy who presented to
our institution with complaint of blurring of vision in the right eye since
birth. A diagnosis of Cornelia de Lange syndrome was arrived at based on the
characteristic external and ophthalmic examination. He was found to have a rare
association of optic nerve head coloboma in the right eye and a novel finding of
an optic disk pit in the left eye. The association of optic disk pit with CdLS
has never been reported earlier. We aim to provide a thorough review of
literature of this not so uncommon syndrome.
PMID- 25136231
TI - Bilateral simultaneous nonarteritic anterior ischemic optic neuropathy in a
patient with alcoholic liver disease.
AB - A 53-year-old man with a history of alcoholism since 10 years admitted for
jaundice elsewhere developed bilateral simultaneous decrease in vision in both
the eyes 4 days after admission. His best-corrected visual acuity was 20/20 in
both eyes. Visual field evaluation revealed an inferior altitudinal defect in
both the eyes. Optic disc appearance, visual fields, and optical coherence
tomography of discs were suggestive of nonarteritic anterior ischemic optic
neuropathy (NAION) in both the eyes. Liver function tests revealed elevated serum
bilirubin and hepatic enzymes. He was negative for hepatitis B virus (HBV) and
hepatitis C virus (HCV) infection. Abdominal ultrasound revealed no focal hepatic
lesion, and carotid doppler revealed no arteriosclerosis. A diagnosis of
bilateral ischemic optic neuropathy associated with alcoholic hepatitis was made.
Bilateral simultaneous NAION has been previously reported in perioperative visual
loss, HCV infection, and interferon treatment. This is the first case report of
bilateral simultaneous NAION in alcoholic hepatitis in the absence of associated
infective viral hepatitis. We explore the pathophysiology of ischemic optic
neuropathy in liver disease. An early intervention to correct the risk factors
leading to NAION may help in preventing this vision-threatening complication in
patients with chronic liver disease.
PMID- 25136232
TI - Rapid regression of choroidal metastasis from lung cancer using erlotinib
(Tarceva).
AB - Lung carcinoma is the leading cause of cancer-related deaths and is the primary
source for choroidal metastasis in over 20% cases. Non-small-cell lung cancer
(NSCLC) accounts for 85% of all lung cancer cases. Patients with metastatic NSCLC
have a median survival of one year. Successful treatment of systemic metastasis
from NSCLC using erlotinib has been documented. The effect of oral erlotinib on
choroidal metastasis has been rarely reported. We document a case and study the
effect of oral erlotinib on choroidal metastasis from NSCLC. A 48-year-old
Caucasian female presented with biopsy-proven primary NSCLC with systemic
metastasis and solitary choroidal metastasis of 4.8 mm thickness in the right
eye. The patient was treated with 100 mg daily dose of oral erlotinib. Two weeks
after starting erlotinib therapy, the patient showed complete regression of
choroidal metastasis to a flat scar with resolution of subretinal fluid and
improvement of visual acuity from 20/100 to 20/25. There was no evidence of
recurrence at five-month follow-up. Erlotinib is an alternative therapy for
choroidal metastasis from NSCLC.
PMID- 25136233
TI - Long-term results of intravitreal ranibizumab for osteoma-related choroidal
neovascularization in a child.
AB - Though choroidal osteoma is a rare benign tumor, associated choroidal
neovascularization (CNV) can be a cause of severe visual loss. A nine-year-old
boy presented with one-month history of decreased vision in left eye. Upon a
complete ophthalmologic examination, including fundus fluorescein angiography and
optical coherence tomography, he was diagnosed with choroidal osteoma-related
subfoveal CNV in the left eye. The CNV was associated with subretinal hemorrhage,
subretinal fluid, and cystoid macular edema. Owing to the young age and subfoveal
localization of the CNV, intravitreal ranibizumab injection was performed on this
patient after a detailed discussion with the parents of its safety profile. No
local or systemic complications were noted. No recurrence of CNV lesion was noted
during 30 months of follow-up, and the vision was maintained. This report shows
the favorable outcome of intravitreal injection of ranibizumab in choroidal
osteoma-related CNV in a child.
PMID- 25136235
TI - Optical coherence tomography demonstrating macular retinal nerve fiber thinning
in advanced optic disc drusen.
AB - Optic disc drusen (ODD) are extracellular proteinaceous excrescences in the optic
nerve head. They enlarge over time and can cause damage to nerve fibers with
resulting loss of visual field. The authors report a case of advanced ODD in
which macular optical coherence tomography demonstrated retinal nerve fiber
thinning. A single case report of a 42-year-old woman with known ODD presented to
the eye clinic with worsening field of vision which was impacting on her daily
life. The patient was subject to full ophthalmic examination as well as Goldmann
visual field testing, optic disc photography and optical coherence tomography
(OCT) of both her optic discs and maculae. ODD although rare, can be visually
devastating. No treatment is currently available however patients should be
counseled about progressive nature of ODD and the potential for visual loss. OCT
imaging of the maculae as well as optic discs may serve a role in monitoring the
damage disc drusen cause to the eye.
PMID- 25136234
TI - Giant leiomyoma of the ciliary body.
AB - Leiomyoma is a rare intraocular tumor that arises from uveal smooth muscle.
Herein, we report a large leiomyoma that occupied nearly 50% of the globe,
closely resembling melanoma. A 40-year-old female presented with a 17 * 15 * 11
mm amelanotic ciliochoroidal mass causing visual defect in her right eye (OD).
Based on transillumination features of tumor shadow and ultrasonographic features
of acoustically solid mass, there was low clinical suspicion for leiomyoma or
schwannoma, and a preliminary diagnosis of ciliochoroidal melanoma was rendered.
Following enucleation, histopathology revealed a paucicellular tumor comprised of
spindle cells, with positive immunostaining for smooth muscle actin and negative
stains for melanoma markers (S-100 protein, HMB45, and MITF-2). These features
were consistent with ciliochoroidal leiomyoma. Benign uveal leiomyoma can achieve
an unusually large size and block light transmission on transillumination,
features that simulate malignant melanoma.
PMID- 25136236
TI - Alternating central serous chorioretinopathy in two consecutive pregnancies.
AB - To highlight the similarity in onset, clinical course, and resolution of central
serous chorioretinopathy in two eyes, in two consecutive pregnancies in the same
patient. A case report. Snellen visual acuity, slit-lamp examination, and optical
coherence tomography (OCT). A 31-year-old female had central serous
chorioretinopathy with sub-retinal exudates in left eye during the sixth month of
her first pregnancy and later in right eye also during the sixth month of her
second pregnancy two years later. Both eyes had spontaneous resolution of the
lesions with final visual acuity of 1.0 each eye. To the best of our knowledge,
there have been no reports of alternating CSCR with sub-retinal exudates,
occurring exactly in the sixth month of two consecutive pregnancies, two years
apart, with spontaneous resolution after deliveries.
PMID- 25136238
TI - Medulloepithelioma: A triad of clinical features.
AB - BACKGROUND: Intraocular medulloepithelioma arises from the primitive medullary
epithelium and is diagnosed at a median age of five years. This tumor most
commonly appears as a white, gray, or yellow-colored ciliary body tumor. The
growth of medulloepithelioma is slow and it is locally invasive. Poor vision and
pain are the most common presenting symptoms. The most common clinical signs
include cyst or mass in iris, anterior chamber or ciliary body, glaucoma, and
cataract. CASE: A 22-month-old Caucasian female twin presented with leukocoria
and poor vision in OS. Examination revealed normal findings OD and a mass in OS.
Based on the clinical features of leukocoria, lens changes and a white cystic
ciliary body mass in a young child, ultrasonographic, and transillumination
features, the lesion was diagnosed as a non-pigmented ciliary epithelial
medulloepithelioma. After enucleation, the diagnosis of malignant teratoid
medulloepithelioma of the non-pigmented ciliary epithelium was confirmed. There
was no evidence of tumor recurrence or systemic metastasis at three years follow
up. CONCLUSION: Medulloepithelioma in a child can present as a clinical triad of
leukocoria, lens changes, and a white cystic ciliary body mass.
PMID- 25136237
TI - OLOGEN((r)) implant in the management of glaucoma in an unusual case of Axenfeld
Rieger syndrome.
AB - We report an unusual case of Axenfeld-Rieger Syndrome with secondary glaucoma
managed with Ologen((r)) implant. A 35-year-old male presented with complaints of
decreased vision in both eyes of 22 years duration. His best corrected visual
acuity (BCVA) was no perception of light in right eye and 20/30 in left eye.
Gonioscopy revealed anterior insertion of iris into trabecular meshwork,
prominent iris processes and broad-based synechiae with prominent Schwalbe's line
along the angle circumference with cord-like structures taking its origin at the
level of Schwalbe's line in both eyes. Fundus examination revealed total
glaucomatous optic atrophy in right eye with 0.9:1 cup disc ratio with bipolar
notch in left eye. Humphrey visual field analysis showed superior and inferior
arcuate scotoma in left eye. Intraocular pressure measured by Goldman applanation
tonometry was 30 mmHg and 26 mmHg in right and left eye, respectively. After an
unsuccessful medical management, he underwent trabeculectomy with Ologen((r))
implant under local anesthesia in his left eye. Postoperatively, at the end of
one year, intraocular pressure (IOP) in his left eye was controlled without
medication. This case highlights the management of secondary angle closure
glaucoma in Axenfeld-Rieger syndrome with Ologen((r)) implant.
PMID- 25136239
TI - Branch retinal artery occlusion associated with congenital retinal macrovessel.
AB - A congenital retinal macrovessel (CRM) is a large retinal vessel, usually a vein,
which traverses through the central macula and has large tributaries extending on
both sides of the horizontal raphe. In the majority of cases, CRM have no effect
on visual acuity, although in rare cases, macular hemorrhage, foveolar cysts,
serous macular detachment, and the presence of the anomalous vessel in the
foveola can affect vision. We describe a case of CRM with decreased vision
secondary to a branch retinal artery occlusion (BRAO). To the best of our
knowledge, this association has not been reported previously.
PMID- 25136240
TI - Congenital total eversion of upper eyelids in a newborn with Down's syndrome.
PMID- 25136242
TI - Progressive Painless Loss of Vision - What is the diagnosis?
PMID- 25136241
TI - Fundus autofluorescence imaging to document evolution, progression and healing
pattern of serpiginous choroiditis.
PMID- 25136243
TI - Complete third nerve palsy: Only presenting sign of extradural hematoma in an
awake patient.
PMID- 25136244
TI - Retinal pigment epithelial tear after intravitreal bevacizumab injection for
exudative age-related macular degeneration.
PMID- 25136245
TI - An unusual case of posterior cerebral artery infarct in otherwise healthy man.
PMID- 25136247
TI - In-house drug diversion by hospital personnel.
PMID- 25136246
TI - Comparison between helical computed tomography angiography and intraoperative
findings.
AB - BACKGROUND: Live donor nephrectomy has gained popularity on account of the
laparoscopic technique, to overcome a small donor pool. Laparoscopic donor
nephrectomy requires a precise study of the vascular and morphological renal
anatomy, as laparoscopy is technically challenging due to the limited field of
vision. In-depth knowledge of the renal anatomy before a laparoscopic procedure
is essential for a successful transplant. The left kidney is preferred over the
right even in cases of multiple vessels because of the long renal vein, which
requires precise preoperative vascular mapping. Helical computerized tomography
(CT) angiography, with its axial, coronal, and 3D reconstruction, gives a better
understanding of renal anatomy. There are instances where the helical CT findings
are misleading and less informative in a small number of cases. This study
highlights a case study of the helical CT findings compared with the
intraoperative findings of 200 live donors, who underwent laparoscopic donor
nephrectomy, and the renal anatomy has been understood at the same time. AIMS: 1.
To compare the helical CT findings on the operated side with the intraoperative
findings. 2. To analyze the CT findings. MATERIALS AND METHODS: Two hundred cases
of laparoscopic transperitoneal donor nephrectomy were included in this study.
STATISTICAL METHOD USED: Chi square test was the statistical test used to compare
the findings between CT and the intraoperative data. RESULTS: The axial, coronal,
and 3D images of the CT findings were on par with the intraoperative findings in
most of the cases. Incidental findings help in the better planning of surgery.
Multiple vessels on the left side are preferred over the right sided normal
anatomy; with not much technical difficulty with the aid of a helical CT. Male
donors had more incidences of multiple vessels, gonadal vein, Retroaortic Renal
Vein (RARV), lumbar vein, and duplication of ureter, compared to females.
Furthermore, these variations are more in the left side donors. Ninety-two
percent of the cases in this study are left-sided donors. The helical CT finding
shows that renal vein variations are more on the right side. CONCLUSIONS: Helical
CT is important in delineating the arterial, venous, and ureteral anatomy and can
show the important incidental findings. Left renal donors and males have more
variations in their renal anatomy. Technically challenging laparoscopic
nephrectomy on the multiple-vessel-side donor is possible with the aid of helical
CT. The importance of the CT in evaluating donor renal anatomy for a technically
challenging laparoscopic donor nephrectomy is commendable.
PMID- 25136248
TI - Oops, Sorry, Wrong Patient!: A Patient Verification Process is Needed Everywhere,
Not Just at the Bedside.
AB - Verification of patient identity is needed at all stages.
PMID- 25136249
TI - HHS Alters Formulary Exception Policy for 2015: QHPs Must Respond Within 24 Hours
to "Expedited" Requests.
AB - HHS adjusts its formulary "exception" policy for 2015.
PMID- 25136251
TI - Pharmaceutical approval update.
AB - Vedolizumab (Entyvio) for ulcerative colitis and Crohn's disease; dalbavancin
(Dalvance) for acute bacterial skin and skin structure infections; and
antihemophilic factor, recombinant (Eloctate) for hemophilia A.
PMID- 25136252
TI - Tedizolid phosphate (sivextro): a second-generation oxazolidinone to treat acute
bacterial skin and skin structure infections.
AB - Tedizolid phosphate: a second-generation oxazolidinone for acute bacterial skin
and skin structure infections.
PMID- 25136253
TI - Legal risk management opportunities, pharmacy practice, and p&t committees: part
1: deconstructing dispensing errors.
AB - A comprehensive analysis of malpractice claims experience from a professional
liability insurer, Healthcare Providers Service Organization, can help P&T
committees better understand the risks and challenges they encounter each day.
PMID- 25136254
TI - Are specialty drug prices destroying insurers and hurting consumers?: a number of
efforts are under way to reduce price pressure.
AB - Organizations are trying to address the high cost of "specialty" medications that
treat conditions such as cancer, hepatitis C, and multiple sclerosis. While
comprising less than 1% of U.S. prescriptions, these drugs now account for 27% of
pharmacy spending.
PMID- 25136256
TI - Ulcerative colitis and Crohn's disease.
AB - As new drugs emerge from the pipeline for the nearly 2 billion patients globally
diagnosed with ulcerative colitis and Crohn's disease, sales of therapies for
these conditions are expected to increase from $7.35 billion today to $11.05
billion in 2022.
PMID- 25136255
TI - Irritable bowel syndrome: current and emerging treatment options.
AB - Irritable bowel syndrome, a functional gastrointestinal disorder of uncertain
pathophysiology, affects up to 55 million Americans. Medications available or in
development include antispasmodics, antidepressants, and antidiarrheals.
PMID- 25136257
TI - Rosiglitazone enhances apolipoprotein M (Apom) expression in rat's liver.
AB - Apolipoprotein M (APOM) has been suggested as a vasculoprotective constituent of
high density lipoprotein (HDL), which plays a crucial role behind the mechanism
of HDL-mediated anti-atherosclerosis. Previous studies demonstrated that insulin
resistance could associate with decreased APOM expressions. In agreement with our
previous reports, here, we further confirmed that the insulin sensitivity was
also reduced in rats treated with high concentrations of glucose; such effect
could be reversed by administration of rosiglitazone, a peroxisome proliferator
activated receptor-gamma (PPARgamma). The present study shows that Apom
expression is significantly affected by either rosiglitazone or hyperglycemia
alone without cross interaction with each other, which indicates that the pathway
of Apom expression regulating by hyperglycemia might be differed from that by
rosiglitazone. Further study indicated that hyperglycemia could significantly
inhibit mRNA levels of Lxrb (P=0.0002), small heterodimer partner 1 (Shp1)
(P<0.0001), liver receptor homologue-1 (Lrh1) (P=0.0012), ATP-binding cassette
transporter 1 (Abca1) (P=0.0012) and Pparb/d (P=0.0043). Two-way ANOVA analysis
demonstrated that the interactions between rosiglitazone and infusion of 25%
glucose solution on Shp1 (P=0.0054) and Abca1 (4E, P=0.0004) mRNA expression was
statistically significant. It is concluded that rosiglitazone could increase Apom
expression, of which the detailed mechanism needs to be further investigated. The
downregulation of Apom by hyperglycemia might be mainly through decreasing
expression of Pparg and followed by inhibiting Lxrb in rats.
PMID- 25136258
TI - Three-dimensional culture environment increases the efficacy of platelet rich
plasma releasate in prompting skin fibroblast differentiation and extracellular
matrix formation.
AB - Platelet rich plasma clot- releasate (PRCR) shows significant influence on tissue
regeneration in clinical trials. Although, the mechanism of PRCR effect on
fibroblast differentiation has been studied on 2D culture system, a detailed
investigation is needed to establish the role of PRCR in cell seeded in 3D
scaffolds. Therefore, a study was conducted to evaluate the influence of PRCR in
fibroblasts (DFB) differentiation and extracellular matrix formation on both 3D
and 2D culture systems. Cell viability was measured using MTT assay and DFB
differentiation was evaluated by determining the expression levels of
nucleostamin and alpha smooth muscle actin (alpha-SMA), using indirect
immunostaining and Western blotting. The expression levels of extracellular
matrix genes (collagen-I, collagen-III, fibronectin and laminin) and focal
adhesion formation gene (integrin beta-1) were measured using Real-time PCR. The
PRCR at 10% showed significant effect on cells viability compared with 5% and 20%
in both culture environments. The decrease in the expression levels of
nucleostamin and the increase in alpha-SMA signify the DFB differentiation to
myofibroblast-like cells that was prominently greater in 3D compared to 2D
culture. In 3D culture systems, the total collage production, expression levels
of the extracellular matrix gene and the focal adhesion gene were increased
significantly compared to 2D culture. In conclusion, 3D culture environments
enhances the proliferative and differentiation effects of PRCR on DFB, thereby
potentially increases the efficacy of DFB for future tissue engineering clinical
application.
PMID- 25136259
TI - Research progress on vertebrobasilar dolichoectasia.
AB - Vertebrobasilar dolichoectasia (VBD) is a rare disease characterized by
significant expansion, elongation, and tortuosity of the vertebrobasilar
arteries. Current data regarding VBD are very limited. Here we systematically
review VBD incidence, etiology, characteristics, clinical manifestations,
treatment strategies, and prognosis. The exact incidence rate of VBD remains
unclear, but is estimated to be 1.3% of the population. The occurrence of VBD is
thought to be due to the cooperation of multiple factors, including congenital
factors, infections and immune status, and degenerative diseases. The VBD
clinical manifestations are complex with ischemic stroke as the most common,
followed by progressive compression of cranial nerves and the brain stem,
cerebral hemorrhage, and hydrocephalus. Treatment of VBD remains difficult.
Currently, there are no precise and effective treatments, and available
treatments mainly target the complications of VBD. With the development of stent
technology, however, it may become an effective treatment for VBD.
PMID- 25136260
TI - Opposite effects of bone marrow-derived cells transplantation in MPTP-rat model
of Parkinson's disease: a comparison study of mononuclear and mesenchymal stem
cells.
AB - The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model is a useful
tool to study Parkinson's disease (PD) and was used in the present study to
investigate the potential beneficial as well as deleterious effects of systemic
bone-marrow mononuclear cell (BMMC) or mesenchymal stem cell (BM-MSC)
transplantation. MPTP administration resulted in a breakdown of the blood-brain
barrier and motor impairment in the open field test 24 h after surgery. Three and
7 days after receiving the lesion, the injured animals showed remaining motor
impairment compared to the sham groups along with a significant loss of tyrosine
hydroxylase-immunoreactive (TH-ir) cells in the substantia nigra pars compacta
(SNpc). The MPTP-lesioned rats treated with BMMCs immediately after lesioning
exhibited motor impairment similar to the MPTP-saline group, though they
presented a significantly higher loss of TH-ir cells in the SNpc compared to the
MPTP-saline group. This increased loss of TH-ir cells in the SNpc was not
observed when BMMC transplantation was performed 24 h after MPTP administration.
In contrast, in the MPTP animals treated early with systemic BM-MSCs, no loss of
TH-ir cells was observed. BMMCs and BM-MSCs previously labeled with CM-DiI cell
tracker were found in brain sections of all transplanted animals. In addition,
cells expressing CD45, an inflammatory white blood cell marker, were found in all
brain sections analyzed and were more abundant in the MPTP-BMMC animals. In these
animals, Iba1+ microglial cells showed also marked morphological changes
indicating increased microglial activation. These results show that systemic BMMC
transplantation did not ameliorate or prevent the lesion induced by MPTP.
Instead, BMMC transplantation in MPTP-lesioned rats accelerated dopaminergic
neuronal damage and induced motor impairment and immobility behavior. These
findings suggest that caution should be taken when considering cell therapy using
BMMCs to treat PD. However, systemic BM-MSC transplantation that reaches the
injury site and prevents neuronal damage after an MPTP infusion could be
considered as a potential treatment for PD during the early stage of disease
development.
PMID- 25136263
TI - Insomnia among patients with advanced disease during admission in a Palliative
Care Unit: a prospective observational study on its frequency and association
with psychological, physical and environmental factors.
AB - BACKGROUND: THE AIMS OF THIS STUDY WERE: 1) to assess the frequency of insomnia
among patients during admission in a Palliative Care Unit (PCU); 2) to study the
association between emotional distress and insomnia, taking physical,
environmental and other psychological factors into account. METHODS: Prospective
observational study including patients consecutively admitted to a PCU during
eight months, excluding those with severe cognitive problems or too low
performance status. Insomnia was assessed by asking a single question and by
using the Sleep Disturbance Scale (SDS), and emotional distress using the
Hospital Anxiety and Depression Scale (HADS). Physical, environmental and other
psychological factors potentially interfering with sleep quality were evaluated.
Association between insomnia and the factors evaluated was studied using
univariate and multivariate regression analyses. RESULTS: 61 patients were
included (mean age 71.5 years; 95% with oncological disease); 38 (62%) answered
"yes" to the insomnia single question and 29 (47%) showed moderate to severe
insomnia according to the SDS. 65% showed clinically significant emotional
distress and 79% had nocturnal rumination. The physical symptoms most often
mentioned as interfering with sleep quality were pain (69%) and dyspnoea (36%).
77% reported at least one environmental disturbance. In the univariate analysis,
answering "yes" to the insomnia single question was significantly associated with
higher HADS score, anxiety, nocturnal rumination, clear knowledge of the
diagnosis, higher performance status and dyspnoea; moderate to severe insomnia
was significantly associated with nocturnal rumination, higher performance
status, environmental disturbances and daytime sleepiness. In the multivariate
regression analysis, answering "yes" to the single question was associated with
dyspnoea (OR 7.2 [1.65-31.27]; p = 0.009), nocturnal rumination (OR 5.5 [1.05
28.49]; p = 0.04) and higher performance status (OR 14.3 [1.62-125.43]; p =
0.017), and moderate to severe insomnia with nocturnal rumination (OR 5.6 [1.1
29.1]; p = 0.041), and inversely associated with daytime sleepiness (OR 0.25
[0.07-0.9]; p = 0.043). CONCLUSIONS: Insomnia was highly frequent. Several
physical, psychological and environmental factors seemed to influence insomnia.
Within the multimodal management of insomnia, the assessment of nocturnal
rumination may be of particular interest, irrespective of emotional distress.
Further studies with larger sample sizes could confirm this result.
PMID- 25136261
TI - Bone morphogenetic protein-9 induces PDLSCs osteogenic differentiation through
the ERK and p38 signal pathways.
AB - Periodontal ligament stem cells (PDLSCs) with bone morphogenic ability are used
to treat diseases such as periodontitis. Their treatment potential is increased
when used in combination with proteins that induce osteogenic differentiation.
For example, bone morphogenetic protein-9 (BMP9) has been found to have potent
osteogenic activity. In the present study, PDLSCs were isolated from human
periodontal membrane and infected with recombinant adenoviruses expressing BMP9
(Ad-BMP9). Levels of osteogenic markers such as runt-related transcription factor
2 (Runx2), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN)
as well as mineralization ability were measured. The results showed that BMP9
promoted bone formation of PDLSCs. In other experiments, SB203580 and PD98059,
which are inhibitors of p38 and ERK1/2, respectively, were used to determine if
these kinases are involved in the osteogenic differentiation process. The
resulting protein expression profiles and osteogenic markers of PDLSCs revealed
that the mitogen-activated protein kinase (MAPK) signaling pathway might play an
important role in the process of BMP9-induced osteogenic differentiation of
PDLSCs.
PMID- 25136264
TI - Age- and sex-specific spatio-temporal patterns of colorectal cancer mortality in
Spain (1975-2008).
AB - In this paper, space-time patterns of colorectal cancer (CRC) mortality risks are
studied by sex and age group (50-69, >=70) in Spanish provinces during the period
1975-2008. Space-time conditional autoregressive models are used to perform the
statistical analyses. A pronounced increase in mortality risk has been observed
in males for both age-groups. For males between 50 and 69 years of age, trends
seem to stabilize from 2001 onward. In females, trends reflect a more stable
pattern during the period in both age groups. However, for the 50-69 years group,
risks take an upward trend in the period 2006-2008 after the slight decline
observed in the second half of the period. This study offers interesting
information regarding CRC mortality distribution among different Spanish
provinces that could be used to improve prevention policies and resource
allocation in different regions.
PMID- 25136262
TI - Astragaloside IV alleviates early brain injury following experimental
subarachnoid hemorrhage in rats.
AB - Astragaloside IV, one of the main effective components isolated from Astragalus
membranaceus, has multiple neuroprotective properties, while the effects of
astragaloside IV on the attenuation of subarachnoid hemorrhage (SAH)-induced
early brain injury (EBI) and its possible mechanisms are unknown. In the present
study, we aimed to determine whether astragaloside IV could inhibit oxidative
stress, reduce neuronal apoptosis, and improve neurological deficits after
experimental SAH in rats. Rats (n=68) were randomly divided into the following
groups: Sham group, SAH group, SAH+vehicle group, and SAH+astragaloside IV group.
Astragaloside IV or an equal volume of vehicle was administered at 1 h and 6 h
after SAH, all the rats were subsequently sacrificed at 24 h after SAH.
Mortality, neurological scores, and brain edema were assessed, biochemical tests
and histological studies were also performed at that point. SAH induced an
increase in the malondialdehyde (MDA) level, neuronal apoptosis, cleaved caspase
3, brain edema and decreased activities of superoxide dismutase (SOD) and
glutathione peroxidase (GSH-Px). Astragaloside IV treatment reversed these
changes and improved neurobehavioral outcomes of SAH rats. Our findings suggested
that astragaloside IV may alleviate EBI after SAH through antioxidative and anti
apoptotic effects.
PMID- 25136265
TI - Blau syndrome, the prototypic auto-inflammatory granulomatous disease.
AB - Blau syndrome is a monogenic disease resulting from mutations in the pattern
recognition receptor NOD2, and is phenotypically characterized by the triad of
granulomatous polyarthritis, dermatitis and uveitis. This paper reviews briefly
the classical clinical features of the disease, as well as more recently
described extra-triad symptoms. From an ongoing prospective multicenter study, we
provide new data on the natural history of Blau syndrome, focusing on functional
status and visual outcome. We also present an update of the range of different
NOD2 mutations found in Blau syndrome as well as recent data on morphologic and
immunohistochemical characteristics of the Blau granuloma. Finally, emerging
insights into pathogenic mechanisms including activation of NOD2 signal
transduction, and potential biomarkers of disease activity are discussed.
PMID- 25136266
TI - A Coarse-Grained Model of Unstructured Single-Stranded DNA Derived from Atomistic
Simulation and Single-Molecule Experiment.
AB - A simple coarse-grained model of single-stranded DNA (ssDNA) was developed,
featuring only two sites per nucleotide that represent the centers of mass of the
backbone and sugar/base groups. In the model, the interactions between sites are
described using tabulated bonded potentials optimized to reproduce the solution
structure of DNA observed in atomistic molecular dynamics simulations. Isotropic
potentials describe nonbonded interactions, implicitly taking into account the
solvent conditions to match the experimentally determined radius of gyration of
ssDNA. The model reproduces experimentally measured force-extension dependence of
an unstructured DNA strand across 2 orders of magnitude of the applied force. The
accuracy of the model was confirmed by measuring the end-to-end distance of a
dT14 fragment via FRET while stretching the molecules using optical tweezers. The
model offers straightforward generalization to systems containing double-stranded
DNA and DNA binding proteins.
PMID- 25136268
TI - Computing the Free Energy Barriers for Less by Sampling with a Coarse Reference
Potential while Retaining Accuracy of the Target Fine Model.
AB - Proposed in this contribution is a protocol for calculating fine-physics (e.g.,
ab initio QM/MM) free-energy surfaces at a high level of accuracy locally (e.g.,
only at reactants and at the transition state for computing the activation
barrier) from targeted fine-physics sampling and extensive exploratory coarse
physics sampling. The full free-energy surface is still computed but at a lower
level of accuracy from coarse-physics sampling. The method is analytically
derived in terms of the umbrella sampling and the free-energy perturbation
methods which are combined with the thermodynamic cycle and the targeted sampling
strategy of the paradynamics approach. The algorithm starts by computing low
accuracy fine-physics free-energy surfaces from the coarse-physics sampling in
order to identify the reaction path and to select regions for targeted sampling.
Thus, the algorithm does not rely on the coarse-physics minimum free-energy
reaction path. Next, segments of high-accuracy free-energy surface are computed
locally at selected regions from the targeted fine-physics sampling and are
positioned relative to the coarse-physics free-energy shifts. The positioning is
done by averaging the free-energy perturbations computed with multistep linear
response approximation method. This method is analytically shown to provide
results of the thermodynamic integration and the free-energy interpolation
methods, while being extremely simple in implementation. Incorporating the
metadynamics sampling to the algorithm is also briefly outlined. The application
is demonstrated by calculating the B3LYP//6-31G*/MM free-energy barrier for an
enzymatic reaction using a semiempirical PM6/MM reference potential. These
modifications allow computing the activation free energies at a significantly
reduced computational cost but at the same level of accuracy compared to
computing full potential of mean force.
PMID- 25136267
TI - Quantifying the Sources of Kinetic Frustration in Folding Simulations of Small
Proteins.
AB - Experiments and atomistic simulations of polypeptides have revealed structural
intermediates that promote or inhibit conformational transitions to the native
state during folding. We invoke a concept of "kinetic frustration" to quantify
the prevalence and impact of these behaviors on folding rates within a large set
of atomistic simulation data for 10 fast-folding proteins, where each protein's
conformational space is represented as a Markov state model of conformational
transitions. Our graph theoretic approach addresses what conformational features
correlate with folding inhibition and therefore permits comparison among features
within a single protein network and also more generally between proteins.
Nonnative contacts and nonnative secondary structure formation can thus be
quantitatively implicated in inhibiting folding for several of the tested
peptides.
PMID- 25136269
TI - Inferring Microscopic Kinetic Rates from Stationary State Distributions.
AB - We present a principled approach for estimating the matrix of microscopic
transition probabilities among states of a Markov process, given only its
stationary state population distribution and a single average global kinetic
observable. We adapt Maximum Caliber, a variational principle in which the path
entropy is maximized over the distribution of all possible trajectories, subject
to basic kinetic constraints and some average dynamical observables. We
illustrate the method by computing the solvation dynamics of water molecules from
molecular dynamics trajectories.
PMID- 25136270
TI - Drug Resistance Mutations Alter Dynamics of Inhibitor-Bound HIV-1 Protease.
AB - Under the selective pressure of therapy, HIV-1 protease mutants resistant to
inhibitors evolve to confer drug resistance. Such mutations can impact both the
dynamics and structures of the bound and unbound forms of the enzyme. Flap+ is a
multidrug-resistant variant of HIV-1 protease with a combination of primary and
secondary resistance mutations (L10I, G48V, I54V, V82A) and a strikingly altered
thermodynamic profile for darunavir (DRV) binding relative to the wild-type
protease. We elucidated the impact of these mutations on protein dynamics in the
DRV-bound state using molecular dynamics simulations and NMR relaxation
experiments. Both methods concur in that the conformational ensemble and dynamics
of protease are impacted by the drug resistance mutations in Flap+ variant.
Surprisingly this change in ensemble dynamics is different from that observed in
the unliganded form of the same variant (Cai, Y. et al. J. Chem. Theory
Comput.2012, 8, 3452-3462). Our comparative analysis of both inhibitor-free and
bound states presents a comprehensive picture of the altered dynamics in drug
resistant mutant HIV-1 protease and underlies the importance of incorporating
dynamic analysis of the whole system, including the unliganded state, into
revealing drug resistance mechanisms.
PMID- 25136272
TI - Influence of Sequence and Covalent Modifications on Yeast tRNA Dynamics.
AB - Modified nucleotides are prevalent in tRNA. Experimental studies reveal that
these covalent modifications play an important role in tuning tRNA function. In
this study, molecular dynamics (MD) simulations were used to investigate how
modifications alter tRNA dynamics. The X-ray crystal structures of tRNA(Asp),
tRNA(Phe), and tRNA(iMet), both with and without modifications, were used as
initial structures for 333 ns explicit solvent MD simulations with AMBER. For
each tRNA molecule, three independent trajectory calculations were performed,
giving an aggregate of 6 MUs of total MD across six molecules. The global root
mean-square deviations (RMSD) of atomic positions show that modifications only
introduce significant rigidity to the global structure of tRNA(Phe).
Interestingly, RMSDs of the anticodon stem-loop (ASL) suggest that modified tRNA
has a more rigid structure compared to the unmodified tRNA in this domain. The
anticodon RMSDs of the modified tRNAs, however, are higher than those of
corresponding unmodified tRNAs. These findings suggest that the rigidity of the
anticodon stem-loop is finely tuned by modifications, where rigidity in the
anticodon arm is essential for tRNA translocation in the ribosome, and
flexibility of the anticodon is important for codon recognition. Sugar pucker and
water residence time of pseudouridines in modified tRNAs and corresponding
uridines in unmodified tRNAs were assessed, and the results reinforce that
pseudouridine favors the 3'-endo conformation and has a higher tendency to
interact with water. Principal component analysis (PCA) was used to examine
correlated motions in tRNA. Additionally, covariance overlaps of PCAs were
compared for trajectories of the same molecule and between trajectories of
modified and unmodified tRNAs. The comparison suggests that modifications alter
the correlated motions. For the anticodon bases, the extent of stacking was
compared between modified and unmodified molecules, and only unmodified tRNA(Asp)
has significantly higher percentage of stacking time. Overall, the simulations
reveal that the effect of covalent modification on tRNA dynamics is not simple,
with modifications increasing flexibility in some regions of the structure and
increasing rigidity in other regions.
PMID- 25136273
TI - Conformational Transition Pathways of Epidermal Growth Factor Receptor Kinase
Domain from Multiple Molecular Dynamics Simulations and Bayesian Clustering.
AB - The epidermal growth factor receptor (EGFR) is aberrantly activated in various
cancer cells and an important target for cancer treatment. Deep understanding of
EGFR conformational changes between the active and inactive states is of
pharmaceutical interest. Here we present a strategy combining multiply targeted
molecular dynamics simulations, unbiased molecular dynamics simulations, and
Bayesian clustering to investigate transition pathways during the
activation/inactivation process of EGFR kinase domain. Two distinct pathways
between the active and inactive forms are designed, explored, and compared. Based
on Bayesian clustering and rough two-dimensional free energy surfaces, the energy
favorable pathway is recognized, though DFG-flip happens in both pathways. In
addition, another pathway with different intermediate states appears in our
simulations. Comparison of distinct pathways also indicates that disruption of
the Lys745-Glu762 interaction is critically important in DFG-flip while movement
of the A-loop significantly facilitates the conformational change. Our
simulations yield new insights into EGFR conformational transitions. Moreover,
our results verify that this approach is valid and efficient in sampling of
protein conformational changes and comparison of distinct pathways.
PMID- 25136271
TI - Transferring the PRIMO Coarse-Grained Force Field to the Membrane Environment:
Simulations of Membrane Proteins and Helix-Helix Association.
AB - An extension of the recently developed PRIMO coarse-grained force field to
membrane environments, PRIMO-M, is described. The membrane environment is modeled
with the heterogeneous dielectric generalized Born (HDGB) methodology that simply
replaces the standard generalized Born model in PRIMO without further
parametrization. The resulting model was validated by comparing amino acid
insertion free energy profiles and application in molecular dynamics simulations
of membrane proteins and membrane-interacting peptides. Membrane proteins with
148-661 amino acids show stable root-mean-squared-deviations (RMSD) between 2 and
4 A for most systems. Transmembrane helical peptides maintain helical shape and
exhibit tilt angles in good agreement with experimental or other simulation data.
The association of two glycophorin A (GpA) helices was simulated using replica
exchange molecular dynamics simulations yielding the correct dimer structure with
a crossing angle in agreement with previous studies. Finally, conformational
sampling of the influenza fusion peptide also generates structures in agreement
with previous studies. Overall, these findings suggest that PRIMO-M can be used
to study membrane bound peptides and proteins and validates the transferable
nature of the PRIMO coarse-grained force field.
PMID- 25136275
TI - Studies on the annealing and antibacterial properties of the silver-embedded
aluminum/silica nanospheres.
AB - Substantial silver-embedded aluminum/silica nanospheres with uniform diameter and
morphology were successfully synthesized by sol-gel technique. After various
annealing temperatures, the surface mechanisms of each sample were analyzed using
scanning electron microscope, transmission electron microscope, and X-ray
photoelectron spectroscopy. The chemical durability examinations and
antibacterial tests of each sample were also carried out for the confirmation of
its practical usage. Based on the result of the above analyses, the silver
embedded aluminum/silica nanospheres are eligible for fabricating antibacterial
utensils.
PMID- 25136274
TI - Hamiltonian Switch Metropolis Monte Carlo Simulations for Improved Conformational
Sampling of Intrinsically Disordered Regions Tethered to Ordered Domains of
Proteins.
AB - There is growing interest in the topic of intrinsically disordered proteins
(IDPs). Atomistic Metropolis Monte Carlo (MMC) simulations based on novel
implicit solvation models have yielded useful insights regarding sequence
ensemble relationships for IDPs modeled as autonomous units. However, a majority
of naturally occurring IDPs are tethered to ordered domains. Tethering introduces
additional energy scales and this creates the challenge of broken ergodicity for
standard MMC sampling or molecular dynamics that cannot be readily alleviated by
using generalized tempering methods. We have designed, deployed, and tested our
adaptation of the Nested Markov Chain Monte Carlo sampling algorithm. We refer to
our adaptation as Hamiltonian Switch Metropolis Monte Carlo (HS-MMC) sampling. In
this method, transitions out of energetic traps are enabled by the introduction
of an auxiliary Markov chain that draws conformations for the disordered region
from a Boltzmann distribution that is governed by an alternative potential
function that only includes short-range steric repulsions and conformational
restraints on the ordered domain. We show using multiple, independent runs that
the HS-MMC method yields conformational distributions that have similar and
reproducible statistical properties, which is in direct contrast to standard MMC
for equivalent amounts of sampling. The method is efficient and can be deployed
for simulations of a range of biologically relevant disordered regions that are
tethered to ordered domains.
PMID- 25136277
TI - Tuning of strain and surface roughness of porous silicon layers for higher
quality seeds for epitaxial growth.
AB - Sintered porous silicon is a well-known seed for homo-epitaxy that enables
fabricating transferrable monocrystalline foils. The crystalline quality of these
foils depends on the surface roughness and the strain of this porous seed, which
should both be minimized. In order to provide guidelines for an optimum foil
growth, we present a systematic investigation of the impact of the thickness of
this seed and of its sintering time prior to epitaxial growth on strain and
surface roughness. Strain and surface roughness were monitored in monolayers and
double layers with different porosities as a function of seed thickness and of
sintering time by high-resolution X-ray diffraction and profilometry,
respectively. Unexpectedly, we found that strain in double and monolayers evolves
in opposite ways with respect to layer thickness. This suggests that an
interaction between layers in multiple stacks is to be considered. We also found
that if higher seed thickness and longer annealing time are to be preferred to
minimize the strain in double layers, the opposite is required to achieve
smoother layers. The impact of these two parameters may be explained by
considering the morphological evolution of the pores upon sintering and, in
particular, the disappearance of interconnections between the porous seed and the
bulk as well as the enlargement of pores near the surface. An optimum epitaxial
growth hence calls for a trade-off in seed thickness and annealing time, between
minimum-strained layers and rougher surfaces. PACS CODES: 81.40.-z Treatment of
materials and its effects on microstructure, nanostructure, and properties;
81.05.Rm Porous materials; granular materials; 82.80.Ej X-ray, Mossbauer and
other gamma-ray spectroscopic analysis methods.
PMID- 25136276
TI - Fabrication of low-density GaN/AlN quantum dots via GaN thermal decomposition in
MOCVD.
AB - With an appropriate high anneal temperature under H2 atmosphere, GaN quantum dots
(QDs) have been fabricated via GaN thermal decomposition in metal organic
chemical vapor deposition (MOCVD). Based on the characterization of atomic force
microscopy (AFM), the obtained GaN QDs show good size distribution and have a low
density of 2.4 * 10(8) cm(-2). X-ray photoelectron spectroscopy (XPS) analysis
demonstrates that the GaN QDs were formed without Ga droplets by thermal
decomposition of GaN.
PMID- 25136278
TI - Tuning the peak position of subwavelength silica nanosphere broadband
antireflection coatings.
AB - Subwavelength nanostructures are considered as promising building blocks for
antireflection and light trapping applications. In this study, we demonstrate
excellent broadband antireflection effect from thin films of monolayer silica
nanospheres with a diameter of 100 nm prepared by Langmuir-Blodgett method on
glass substrates. With a single layer of compact silica nanosphere thin film
coated on both sides of a glass, we achieved maximum transmittance of 99% at 560
nm. Furthermore, the optical transmission peak of the nanosphere thin films can
be tuned over the UV-visible range by changing processing parameters during
Langmuir-Blodgett deposition. The tunable optical transmission peaks of the
Langmuir-Blodgett films were correlated with deposition parameters such as
surface pressure, surfactant concentration, ageing of suspensions and annealing
effect. Such peak-tunable broadband antireflection coating has wide applications
in diversified industries such as solar cells, windows, displays and lenses.
PMID- 25136280
TI - Controllable preparation of Ni nanoparticles for catalysis of coiled carbon
fibers growth.
AB - The mass preparation of high-purity coiled carbon fibers (CCFs) remains
challenging due to the high complexity and low controllability of reaction. In
this work, a controllable growth of Ni particles was fulfilled by liquid phase
reduction of nickel sulfate with hydrazine hydrate. The impacts of the reaction
temperature, NaOH concentration, and reaction time on the particle size and
purity were investigated. The as-deposited Ni particles were characterized by
scanning electron microscopy and X-ray diffraction. In addition, these Ni
particles were also applied in preparing high-purity CCFs both on graphite and
ceramic substrates. The diameter of the as-grown carbon microcoil was about 500
nm, and the related growth mechanism was discussed.
PMID- 25136279
TI - Copper pillar and memory characteristics using Al2O3 switching material for 3D
architecture.
AB - A novel idea by using copper (Cu) pillar is proposed in this study, which can
replace the through-silicon-vias (TSV) technique in future three-dimensional (3D)
architecture. The Cu pillar formation under external bias in an Al/Cu/Al2O3/TiN
structure is simple and low cost. The Cu pillar is formed in the Al2O3 film under
a small operation voltage of <5 V and a high-current-carrying conductor of >70 mA
is obtained. More than 100 devices have shown tight distribution of the Cu
pillars in Al2O3 film for high current compliance (CC) of 70 mA. Robust read
pulse endurances of >10(6) cycles are observed with read voltages of -1, 1, and 4
V. However, read endurance is failed with read voltages of -1.5, -2, and -4 V. By
decreasing negative read voltage, the read endurance is getting worst, which is
owing to ruptured Cu pillar. Surface roughness and TiO x N y on TiN bottom
electrode are observed by atomic force microscope and transmission electron
microscope, respectively. The Al/Cu/Al2O3/TiN memory device shows good bipolar
resistive switching behavior at a CC of 500 MUA under small operating voltage of
+/-1 V and good data retention characteristics of >10(3) s with acceptable
resistance ratio of >10 is also obtained. This suggests that high-current
operation will help to form Cu pillar and lower-current operation will have
bipolar resistive switching memory. Therefore, this new Cu/Al2O3/TiN structure
will be benefited for 3D architecture in the future.
PMID- 25136281
TI - Enhanced antibacterial and anti-biofilm activities of silver nanoparticles
against Gram-negative and Gram-positive bacteria.
AB - Silver nanoparticles (AgNPs) have been used as antibacterial, antifungal,
antiviral, anti-inflammtory, and antiangiogenic due to its unique properties such
as physical, chemical, and biological properties. The present study was aimed to
investigate antibacterial and anti-biofilm activities of silver nanoparticles
alone and in combination with conventional antibiotics against various human
pathogenic bacteria. Here, we show that a simple, reliable, cost effective and
green method for the synthesis of AgNPs by treating silver ions with leaf extract
of Allophylus cobbe. The A. cobbe-mediated synthesis of AgNPs (AgNPs) was
characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction
(XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron
spectroscopy (XPS), dynamic light scattering (DLS), and transmission electron
microscopy (TEM). Furthermore, the antibacterial and anti-biofilm activity of
antibiotics or AgNPs, or combinations of AgNPs with an antibiotic was evaluated
using a series of assays: such as in vitro killing assay, disc diffusion assay,
biofilm inhibition, and reactive oxygen species generation in Pseudomonas
aeruginosa, Shigella flexneri, Staphylococcus aureus, and Streptococcus
pneumonia. The results suggest that, in combination with antibiotics, there were
significant antimicrobial and anti-biofilm effects at lowest concentration of
AgNPs using a novel plant extract of A. cobbe, otherwise sublethal concentrations
of the antibiotics. The significant enhancing effects were observed for
ampicillin and vancomycin against Gram-negative and Gram-positive bacteria,
respectively. These data suggest that combining antibiotics and biogenic AgNPs
can be used therapeutically for the treatment of infectious diseases caused by
bacteria. This study presented evidence of antibacterial and anti-biofilm effects
of A. cobbe-mediated synthesis of AgNPs and their enhanced capacity against
various human pathogenic bacteria. These results suggest that AgNPs could be used
as an adjuvant for the treatment of infectious diseases.
PMID- 25136282
TI - Pyrolysis and co-pyrolysis of Laminaria japonica and polypropylene over
mesoporous Al-SBA-15 catalyst.
AB - The catalytic co-pyrolysis of a seaweed biomass, Laminaria japonica, and a
typical polymer material, polypropylene, was studied for the first time. A
mesoporous material Al-SBA-15 was used as a catalyst. Pyrolysis experiments were
conducted using a fixed-bed reactor and pyrolysis gas chromatography/mass
spectrometry (Py-GC/MS). BET surface area, N2 adsorption-desorption isotherms,
and NH3 temperature programmed desorption were measured to examine the catalyst
characteristics. When only L. japonica was pyrolyzed, catalytic reforming
slightly increased the gas yield and decreased the oil yield. The H2O content in
bio-oil was increased by catalytic reforming from 42.03 to 50.32 wt% due to the
dehydration reaction occurring on the acid sites inside the large pores of Al-SBA
15. Acids, oxygenates, mono-aromatics, poly aromatic hydrocarbons, and phenolics
were the main components of the bio-oil obtained from the pyrolysis of L.
japonica. Upon catalytic reforming over Al-SBA-15, the main oxygenate species 1,4
anhydro-d-galactitol and 1,5-anhydro-d-manitol were completely removed. When L.
japonica was co-pyrolyzed with polypropylene, the H2O content in bio-oil was
decreased dramatically (8.93 wt% in the case of catalytic co-pyrolysis),
contributing to the improvement of the oil quality. A huge increase in the
content of gasoline-range and diesel-range hydrocarbons in bio-oil was the most
remarkable change that resulted from the co-pyrolysis with polypropylene,
suggesting its potential as a transport fuel. The content of mono-aromatics with
high economic value was also increased significantly by catalytic co-pyrolysis.
PMID- 25136283
TI - Controlled growth of 1D and 2D ZnO nanostructures on 4H-SiC using Au catalyst.
AB - A perfect control of nanostructure growth is a prerequisite for the development
of electronic and optoelectronic device/systems. In this article, we demonstrate
the growth of various ZnO-derived nanostructures, including well-ordered arrays
of high aspect ratio single crystalline nanowires with preferred growth direction
along the [0001] axis, nanowalls, and hybrid nanowire-nanowall structures. The
growths of the various ZnO nanostructures have been carried out on SiC substrates
in a horizontal furnace, using Au thin film as catalyst. From experimental
observations, we have ascribed the growth mechanisms of the different ZnO
nanostructures to be a combination of catalytic-assisted and non-catalytic
assisted vapor-liquid-solid (VLS) processes. We have also found that the
different ZnO nanoarchitectures' material evolution is governed by a Zn cluster
drift effects on the SiC surface mainly driven by growth temperature. Au thin
film thickness, growth time, and temperature are the parameters to optimize in
order to obtain the different ZnO nanoarchitectures.
PMID- 25136284
TI - Improving the performance of dye-sensitized solar cells with TiO2/graphene/TiO2
sandwich structure.
AB - This study investigates the extent to which the TiO2/graphene/TiO2 sandwich
structure improves the performance of dye-sensitized solar cells (DSSCs) over
that of DSSCs with the traditional structure. Studies have demonstrated that the
TiO2/graphene/TiO2 sandwich structure effectively enhances the open circuit
voltage (V oc), short-circuit current density (J sc), and photoelectrical
conversion efficiency (eta) of DSSCs. The enhanced performance of DSSCs with the
sandwich structure can be attributed to an increase in electron transport
efficiency and in the absorption of light in the visible range. The DSSC with the
sandwich structure in this study exhibited a V oc of 0.6 V, a high J sc of 11.22
mA cm(-2), a fill factor (FF) of 0.58, and a calculated eta of 3.93%, which is
60% higher than that of a DSSC with the traditional structure.
PMID- 25136285
TI - Porous silicon Bloch surface and sub-surface wave structure for simultaneous
detection of small and large molecules.
AB - A porous silicon (PSi) Bloch surface wave (BSW) and Bloch sub-surface wave (BSSW)
composite biosensor is designed and used for the size-selective detection of both
small and large molecules. The BSW/BSSW structure consists of a periodic stack of
high and low refractive index PSi layers and a reduced optical thickness surface
layer that gives rise to a BSW with an evanescent tail that extends above the
surface to enable the detection of large surface-bound molecules. Small molecules
were detected in the sensor by the BSSW, which is a large electric field
intensity spatially localized to a desired region of the Bragg mirror and is
generated by the implementation of a step or gradient refractive index profile
within the Bragg mirror. The step and gradient BSW/BSSW sensors are designed to
maximize both resonance reflectance intensity and sensitivity to large molecules.
Size-selective detection of large molecules including latex nanospheres and the
M13KO7 bacteriophage as well as small chemical linker molecules is reported.
PMID- 25136286
TI - Superhydrophobic ZnO networks with high water adhesion.
AB - ZnO structures were deposited using a simple chemical bath deposition technique
onto interdigitated electrodes fabricated by a conventional photolithography
method on SiO2/Si substrates. The X-ray diffraction studies show that the ZnO
samples have a hexagonal wurtzite crystalline structure. The scanning electron
microscopy observations prove that the substrates are uniformly covered by ZnO
networks formed by monodisperse rods. The ZnO rod average diameter and length
were tuned by controlling reactants' concentration and reaction time. Optical
spectroscopy measurements demonstrate that all the samples display bandgap values
and emission bands typical for ZnO. The electrical measurements reveal
percolating networks which are highly sensitive when the samples are exposed to
ammonia vapors, a variation in their resistance with the exposure time being
evidenced. Other important characteristics are that the ZnO rod networks exhibit
superhydrophobicity, with water contact angles exceeding 150 degrees and a high
water droplet adhesion. Reproducible, easily scalable, and low-cost chemical bath
deposition and photolithography techniques could provide a facile approach to
fabricate such ZnO networks and devices based on them for a wide range of
applications where multifunctionality, i.e., sensing and superhydrophobicity,
properties are required. PACS: 81.07.-b; 81.05.Dz; 68.08.Bc.
PMID- 25136287
TI - Photocurrent enhancement mechanisms in bilayer nanofilm-based ultraviolet
photodetectors made from ZnO and ZnS spherical nanoshells.
AB - Hollow-sphere bilayer nanofilm-based ultraviolet light photodetectors made from
ZnO and ZnS spherical nanoshells show enhanced photocurrent, which are comparable
to or even better than those of other semiconductor nanostructures with different
shapes. In this work, the photocurrent enhancement mechanisms of these bilayer
nanofilm-based ultraviolet light photodetectors are explained, which could be
attributed to the strong light absorption based on the whispering gallery mode
resonances, the separation of the photogenerated carriers through the internal
electric field within the bilayer nanofilms, the hopping-like electrical
transport, and the effective charge injection from Cr/Au contacts to the
nanofilms.
PMID- 25136289
TI - Removal of Cr(VI) from Aqueous Solutions Using Powder of Potato Peelings as a Low
Cost Sorbent.
AB - Potato peels which are a low cost, renewable agroindustry by-product were used
for the removal of hexavalent chromium from aqueous effluents. Batch experiments
were carried out with an artificial effluent comprising of potassium dichromate
in deionised water. The effects of the initial hexavalent chromium concentration,
dose of biosorbent, and removal kinetics were explored. An adsorbent dosage of 4
g/L was effective in complete removal of the metal ion, at pH 2.5, in 48 minutes.
The kinetic process of Cr(VI) adsorption onto potato peel powder was tested by
applying pseudo-first-order and pseudo-second-order models as well as the Elovich
kinetic equation to correlate the experimental data and to determine the kinetic
parameters. The adsorption data were correlated by the Langmuir and Freundlich
isotherms. A maximum monolayer adsorption capacity of 3.28 mg/g was calculated
using the Langmuir adsorption isotherm, suggesting a functional group limited
adsorption process. The results confirmed that potato peels are an effective
biosorbent for the removal of hexavalent chromium from effluent.
PMID- 25136288
TI - Proteomic profile of pre - B2 lymphoblasts from children with acute lymphoblastic
leukemia (ALL) in relation with the translocation (12; 21).
AB - BACKGROUND: Until now, the major prognostic factors for pediatric acute
lymphoblastic leukemia (ALL), age, white blood cell count and chromosomal
alterations are initially taken into account for the risk stratification of
patients. In the light of protein marker studies to classify subtypes of Acute
Myeloblastic Leukemia efficiently, we have compared the lymphoblastes proteome in
Childhood ALL in accordance with the presence of t(12;21), indicator of good
prognosis, usually. METHODS: Protein expression in pre-B2 lymphoblastic cells,
collected from residual bone marrow cells after diagnostic procedures, was
analyzed using two dimensional gel electrophoresis protocol. Protein spots whose
average normalized volumes were statistically different in the two patients
groups (n = 13; student t test p < 0.01), were excised. Tryptic peptides were
then analyzed using a nano-LC1200 system coupled to a 6340 Ion Trap mass
spectrometer equipped with a HPLC-chip cube interface. The tandem mass
spectrometry peak lists extracted using the DataAnalysis program, were compared
with the protein database Mascot Daemon. RESULTS: We focused on twelve spots
corresponding to sixteen identified candidate proteins among the 26 found
differentially expressed (p <= 0.05) regarding the presence of t(12;21). Among
over expressed proteins, two proteins were implicated in cellular growth arrest
(i.e. calponine 2, p <= 0.001 and phosphatidylinositol transfer protein beta, p
<= 0.001) in accordance with good prognosis, while two other proteins favored
cell cycle proliferation (i.e. methionine adenosyl transferase 2beta, p <= 0.005
and heterogeneous nuclear ribonucleo-proteins A2 p <= 0.01) and could therefore
be good marker candidates of aggressiveness. Level of expression of proteasome
subunit beta type-2 (p <= 0.01) and protein casein kinase 2alpha (p <= 0.01)
which both favored apoptosis, deubiquitinating enzyme OTUB1 (p <= 0.05) and MLL
septin-like fusion protein MSF-B, septin 9 i4 (p <= 0.01) were in accord with a
good prognosis related to t(12;21) lymphoblasts. CONCLUSION: By drawing up the
protein map of leukemic cells, these new data identified marker candidates of
leukemic aggressiveness and new t(12;21) patients subgroups. These preliminary
results will be in the near future confirmed by using a larger sample of pre-B2
childhood ALLs from national lymphoblastic cell collections.
PMID- 25136290
TI - Single trial prediction of self-paced reaching directions from EEG signals.
AB - Early detection of movement intention could possibly minimize the delays in the
activation of neuroprosthetic devices. As yet, single trial analysis using non
invasive approaches for understanding such movement preparation remains a
challenging task. We studied the feasibility of predicting movement directions in
self-paced upper limb center-out reaching tasks, i.e., spontaneous movements
executed without an external cue that can better reflect natural motor behavior
in humans. We reported results of non-invasive electroencephalography (EEG)
recorded from mild stroke patients and able-bodied participants. Previous studies
have shown that low frequency EEG oscillations are modulated by the intent to
move and therefore, can be decoded prior to the movement execution. Motivated by
these results, we investigated whether slow cortical potentials (SCPs) preceding
movement onset can be used to classify reaching directions and evaluated the
performance using 5-fold cross-validation. For able-bodied subjects, we obtained
an average decoding accuracy of 76% (chance level of 25%) at 62.5 ms before onset
using the amplitude of on-going SCPs with above chance level performances between
875 to 437.5 ms prior to onset. The decoding accuracy for the stroke patients was
on average 47% with their paretic arms. Comparison of the decoding accuracy
across different frequency ranges (i.e., SCPs, delta, theta, alpha, and gamma)
yielded the best accuracy using SCPs filtered between 0.1 to 1 Hz. Across all the
subjects, including stroke subjects, the best selected features were obtained
mostly from the fronto-parietal regions, hence consistent with previous
neurophysiological studies on arm reaching tasks. In summary, we concluded that
SCPs allow the possibility of single trial decoding of reaching directions at
least 312.5 ms before onset of reach.
PMID- 25136292
TI - The desferrioxamine-prochlorperazine coma-clue to the role of dopamine-iron
recycling in the synthesis of hydrogen peroxide in the brain.
PMID- 25136293
TI - Novel endogenous N-acyl amides activate TRPV1-4 receptors, BV-2 microglia, and
are regulated in brain in an acute model of inflammation.
AB - A family of endogenous lipids, structurally analogous to the endogenous
cannabinoid, N-arachidonoyl ethanolamine (Anandamide), and called N-acyl amides
have emerged as a family of biologically active compounds at TRP receptors. N
acyl amides are constructed from an acyl group and an amine via an amide bond.
This same structure can be modified by changing either the fatty acid or the
amide to form potentially hundreds of lipids. More than 70 N-acyl amides have
been identified in nature. We have ongoing studies aimed at isolating and
characterizing additional members of the family of N-acyl amides in both central
and peripheral tissues in mammalian systems. Here, using a unique in-house
library of over 70 N-acyl amides we tested the following three hypotheses: (1)
Additional N-acyl amides will have activity at TRPV1-4, (2) Acute peripheral
injury will drive changes in CNS levels of N-acyl amides, and (3) N-acyl amides
will regulate calcium in CNS-derived microglia. Through these studies, we have
identified 20 novel N-acyl amides that collectively activate (stimulating or
inhibiting) TRPV1-4. Using lipid extraction and HPLC coupled to tandem mass
spectrometry we showed that levels of at least 10 of these N-acyl amides that
activate TRPVs are regulated in brain after intraplantar carrageenan injection.
We then screened the BV2 microglial cell line for activity with this N-acyl amide
library and found overlap with TRPV receptor activity as well as additional
activators of calcium mobilization from these lipids. Together these data provide
new insight into the family of N-acyl amides and their roles as signaling
molecules at ion channels, in microglia, and in the brain in the context of
inflammation.
PMID- 25136291
TI - How may the basal ganglia contribute to auditory categorization and speech
perception?
AB - Listeners must accomplish two complementary perceptual feats in extracting a
message from speech. They must discriminate linguistically-relevant acoustic
variability and generalize across irrelevant variability. Said another way, they
must categorize speech. Since the mapping of acoustic variability is language
specific, these categories must be learned from experience. Thus, understanding
how, in general, the auditory system acquires and represents categories can
inform us about the toolbox of mechanisms available to speech perception. This
perspective invites consideration of findings from cognitive neuroscience
literatures outside of the speech domain as a means of constraining models of
speech perception. Although neurobiological models of speech perception have
mainly focused on cerebral cortex, research outside the speech domain is
consistent with the possibility of significant subcortical contributions in
category learning. Here, we review the functional role of one such structure, the
basal ganglia. We examine research from animal electrophysiology, human
neuroimaging, and behavior to consider characteristics of basal ganglia
processing that may be advantageous for speech category learning. We also present
emerging evidence for a direct role for basal ganglia in learning auditory
categories in a complex, naturalistic task intended to model the incidental
manner in which speech categories are acquired. To conclude, we highlight new
research questions that arise in incorporating the broader neuroscience research
literature in modeling speech perception, and suggest how understanding
contributions of the basal ganglia can inform attempts to optimize training
protocols for learning non-native speech categories in adulthood.
PMID- 25136295
TI - Role of mitochondria ROS generation in ethanol-induced NLRP3 inflammasome
activation and cell death in astroglial cells.
AB - Toll-like receptors (TLRs) and NOD-like receptors (NLRs) are innate immunity
sensors that provide an early/effective response to pathogenic or injury
conditions. We have reported that ethanol-induced TLR4 activation triggers
signaling inflammatory responses in glial cells, causing neuroinflammation and
brain damage. However, it is uncertain if ethanol is able to activate
NLRs/inflammasome in astroglial cells, which is the mechanism of activation, and
whether there is crosstalk between both immune sensors in glial cells. Here we
show that chronic ethanol treatment increases the co-localization of caspase-1
with GFAP(+) cells, and up-regulates IL-1beta and IL-18 in the frontal medial
cortex in WT, but not in TLR4 knockout mice. We further show that cultured
cortical astrocytes expressed several inflammasomes (NLRP3, AIM2, NLRP1, and
IPAF), although NLRP3 mRNA is the predominant form. Ethanol, as ATP and LPS
treatments, up-regulates NLRP3 expression, and causes caspase-1 cleavage and the
release of IL-1beta and IL-18 in astrocytes supernatant. Ethanol-induced
NLRP3/caspase-1 activation is mediated by mitochondrial (m) reactive oxygen
species (ROS) generation because when using a specific mitochondria ROS
scavenger, the mito-TEMPO (500 MUM) or NLRP3 blocking peptide (4 MUg/ml) or a
specific caspase-1 inhibitor, Z-YVAD-FMK (10 MUM), abrogates mROS release and
reduces the up-regulation of IL-1beta and IL-18 induced by ethanol or LPS or ATP.
Confocal microscopy studies further confirm that ethanol, ATP or LPS promotes
NLRP3/caspase-1 complex recruitment within the mitochondria to promote cell death
by caspase-1-mediated pyroptosis, which accounts for ~73% of total cell death
(~22%) and the remaining (~25%) die by caspase-3-dependent apoptosis. Suppression
of the TLR4 function abrogates most ethanol effects on NLRP3 activation and
reduces cell death. These findings suggest that NLRP3 participates, in ethanol
induced neuroinflammation and highlight the NLRP3/TLR4 crosstalk in ethanol
induced brain injury.
PMID- 25136296
TI - Computational modeling of the effects of auditory nerve dysmyelination.
AB - Our previous study showed that exposure to loud sound leading to hearing loss
elongated the auditory nerve (AN) nodes of Ranvier and triggered notable
morphological changes at paranodes and juxtaparanodes. Here we used computational
modeling to examine how theoretical redistribution of voltage gated Na(+), Kv3.1,
and Kv1.1 channels along the AN may be responsible for the alterations of
conduction property following acoustic over-exposure. Our modeling study infers
that changes related to Na(+) channel density (rather than the redistribution of
voltage gated Na(+), Kv3.1, and Kv1.1 channels) is the likely cause of the
decreased conduction velocity and the conduction block observed after acoustic
overexposure (AOE).
PMID- 25136294
TI - Astrocytic modulation of blood brain barrier: perspectives on Parkinson's
disease.
AB - The blood-brain barrier (BBB) is a tightly regulated interface in the Central
Nervous System (CNS) that regulates the exchange of molecules in and out from the
brain thus maintaining the CNS homeostasis. It is mainly composed of endothelial
cells (ECs), pericytes and astrocytes that create a neurovascular unit (NVU) with
the adjacent neurons. Astrocytes are essential for the formation and maintenance
of the BBB by providing secreted factors that lead to the adequate association
between the cells of the BBB and the formation of strong tight junctions. Under
neurological disorders, such as chronic cerebral ischemia, brain trauma,
Epilepsy, Alzheimer and Parkinson's Diseases, a disruption of the BBB takes
place, involving a lost in the permeability of the barrier and phenotypical
changes in both the ECs and astrocytes. In this aspect, it has been established
that the process of reactive gliosis is a common feature of astrocytes during BBB
disruption, which has a detrimental effect on the barrier function and a
subsequent damage in neuronal survival. In this review we discuss the
implications of astrocyte functions in the protection of the BBB, and in the
development of Parkinson's disease (PD) and related disorders. Additionally, we
highlight the current and future strategies in astrocyte protection aimed at the
development of restorative therapies for the BBB in pathological conditions.
PMID- 25136298
TI - Modulation of social behavior by the agouti pigmentation gene.
AB - Agouti is a secreted neuropeptide that acts as an endogenous antagonist of
melanocortin receptors. Mice and rats lacking agouti (called non-agouti) have
dark fur due to a disinhibition of melanocortin signaling and pigment deposition
in the hair follicle. Non-agouti animals have also been reported to exhibit
altered behavior, despite no evidence for the expression of agouti outside the
skin. Here we confirm that non-agouti mice show altered social behavior and
uncover expression of agouti in the preputial gland, a sebaceous organ in the
urinary tract that secretes molecules involved in social behavior. Non-agouti
mice had enlarged preputial glands and altered levels of putative preputial
pheromones and surgical removal of the gland reversed the behavioral phenotype.
These findings demonstrate the existence of an autologous, out-of-skin pathway
for the modulation of social behavior.
PMID- 25136299
TI - Topographical disorientation after ischemic mini infarct in the dorsal
hippocampus: whispers in silence.
AB - Silent focal ischemic mini infarcts in the brain are thought to cause no
clinically overt symptoms. Some populations of hippocampal cells are particularly
sensitive to ischemic events, however, rendering hippocampal functions especially
vulnerable to ischemia-induced deficits. The present study investigated whether
an otherwise silent ischemic mini infarct in the hippocampus (HPC) can produce
impairments in spatial performance in rats. Spatial performance was assessed in
the ziggurat task (ZT) using a 10-trial spatial learning protocol for 4 days
prior to undergoing hippocampal ischemic lesion or sham surgery. Hippocampal
silent ischemia was induced by infusion of endothelin-1 (ET-1), a potent
vasoconstrictor, into either the dorsal or the ventral hippocampus (dHPC and
vHPC). When tested postoperatively in the ZT using a standard testing protocol
for 8 days, rats with hippocampal lesions exhibited no spatial deficit. Although
spatial learning and memory in the ZT were not affected by the ET-1-induced
silent ischemia, rats with dHPC stroke showed more returns when navigating the ZT
as opposed to the vHPC rats. Comparison of region-specific HPC lesions in the
present study indicated that dorsal hippocampal function is critically required
for topographic orientation in a complex environment. Topographic disorientation
as reflected by enhanced return behaviors may represent one of the earliest
predictors of cognitive decline after silent ischemic insult that may be
potentially traced with sensitive clinical examination in humans.
PMID- 25136301
TI - Beyond pain: modeling decision-making deficits in chronic pain.
AB - Risky decision-making seems to be markedly disrupted in patients with chronic
pain, probably due to the high cost that impose pain and negative mood on
executive control functions. Patients' behavioral performance on decision-making
tasks such as the Iowa Gambling Task (IGT) is characterized by selecting cards
more frequently from disadvantageous than from advantageous decks, and by
switching often between competing responses in comparison with healthy controls
(HCs). In the present study, we developed a simple heuristic model to simulate
individuals' choice behavior by varying the level of decision randomness and the
importance given to gains and losses. The findings revealed that the model was
able to differentiate the behavioral performance of patients with chronic pain
and HCs at the group, as well as at the individual level. The best fit of the
model in patients with chronic pain was yielded when decisions were not based on
previous choices and when gains were considered more relevant than losses. By
contrast, the best account of the available data in HCs was obtained when
decisions were based on previous experiences and losses loomed larger than gains.
In conclusion, our model seems to provide useful information to measure each
individual participant extensively, and to deal with the data on a participant-by
participant basis.
PMID- 25136300
TI - Executive function and endocrinological responses to acute resistance exercise.
AB - THIS STUDY HAD THE FOLLOWING TWO AIMS: First, to explore the effects of acute
resistance exercise (RE, i.e., using exercise machines to contract and stretch
muscles) on behavioral and electrophysiological performance when performing a
cognitive task involving executive functioning in young male adults; Second, to
investigate the potential biochemical mechanisms of such facilitative effects
using two neurotrophic factors [i.e., growth hormone (GH) and insulin-like growth
factor-1 (IGF-1)] and the cortisol levels elicited by such an exercise
intervention mode with two different exercise intensities. Sixty young male
adults were recruited and randomly assigned to a high-intensity (HI) exercise
group, moderate-intensity (MI) exercise group, and non-exercise-intervention
(NEI) group. Blood samples were taken, and the behavioral and
electrophysiological indices were simultaneously measured when individuals
performed a Go/No-Go task combined with the Erikson Flanker paradigm at baseline
and after either an acute bout of 30 min of moderate- or high-intensity RE or a
control period. The results showed that the acute RE could not only benefit the
subjects' behavioral (i.e., RTs and accuracy) performance, as found in previous
studies, but also increase the P3 amplitude. Although the serum GH and IGF-1
levels were significantly increased via moderate or high intensity RE in both the
MI and HI groups, the increased serum levels of neurotrophic factors were
significantly decreased about 20 min after exercise. In addition, such changes
were not correlated with the changes in cognitive (i.e., behavioral and
electrophysiological) performance. In contrast, the serum levels of cortisol in
the HI and MI groups were significantly lower after acute RE, and the changes in
cortisol levels were significantly associated with the changes in
electrophysiological (i.e., P3 amplitude) performance. The findings suggest the
beneficial effects of acute RE on executive functioning could be due to changes
in arousal, possibly modulated by the serum cortisol levels.
PMID- 25136297
TI - Unraveling the complexities of circadian and sleep interactions with memory
formation through invertebrate research.
AB - Across phylogeny, the endogenous biological clock has been recognized as
providing adaptive advantages to organisms through coordination of physiological
and behavioral processes. Recent research has emphasized the role of circadian
modulation of memory in generating peaks and troughs in cognitive performance.
The circadian clock along with homeostatic processes also regulates sleep, which
itself impacts the formation and consolidation of memory. Thus, the circadian
clock, sleep and memory form a triad with ongoing dynamic interactions. With
technological advances and the development of a global 24/7 society,
understanding the mechanisms underlying these connections becomes pivotal for
development of therapeutic treatments for memory disorders and to address issues
in cognitive performance arising from non-traditional work schedules.
Invertebrate models, such as Drosophila melanogaster and the mollusks Aplysia and
Lymnaea, have proven invaluable tools for identification of highly conserved
molecular processes in memory. Recent research from invertebrate systems has
outlined the influence of sleep and the circadian clock upon synaptic plasticity.
In this review, we discuss the effects of the circadian clock and sleep on memory
formation in invertebrates drawing attention to the potential of in vivo and in
vitro approaches that harness the power of simple invertebrate systems to
correlate individual cellular processes with complex behaviors. In conclusion,
this review highlights how studies in invertebrates with relatively simple
nervous systems can provide mechanistic insights into corresponding behaviors in
higher organisms and can be used to outline possible therapeutic options to guide
further targeted inquiry.
PMID- 25136302
TI - Reduced resting-state functional connectivity of the somatosensory cortex
predicts psychopathological symptoms in women with bulimia nervosa.
AB - BACKGROUND: Alterations in the resting-state functional connectivity (rs-FC) of
several brain networks have been demonstrated in eating disorders. However, very
few studies are currently available on brain network dysfunctions in bulimia
nervosa (BN). The somatosensory network is central in processing body-related
stimuli and it may be altered in BN. The present study therefore aimed to
investigate rs-FC in the somatosensory network in bulimic women. METHODS: Sixteen
medication-free women with BN (age = 23 +/- 5 years) and 18 matched controls (age
= 23 +/- 3 years) underwent a functional magnetic resonance resting-state scan
and assessment of eating disorder symptoms. Within-network and seed-based
functional connectivity analyses were conducted to assess rs-FC within the
somatosensory network and to other areas of the brain. RESULTS: Bulimia nervosa
patients showed a decreased rs-FC both within the somatosensory network (t = 9.0,
df = 1, P = 0.005) and with posterior cingulate cortex and two visual areas (the
right middle occipital gyrus and the right cuneus) (P = 0.05 corrected for
multiple comparison). The rs-FC of the left paracentral lobule with the right
middle occipital gyrus correlated with psychopathology measures like bulimia (r =
-0.4; P = 0.02) and interoceptive awareness (r = -0.4; P = 0.01). Analyses were
conducted using age, BMI (body mass index), and depressive symptoms as
covariates. CONCLUSION: Our findings show a specific alteration of the rs-FC of
the somatosensory cortex in BN patients, which correlates with eating disorder
symptoms. The region in the right middle occipital gyrus is implicated in body
processing and is known as extrastriate body area (EBA). The connectivity between
the somatosensory cortex and the EBA might be related to dysfunctions in body
image processing. The results should be considered preliminary due to the small
sample size.
PMID- 25136303
TI - Implicit sequence learning in people with Parkinson's disease.
AB - Implicit sequence learning involves learning about dependencies in sequences of
events without intent to learn or awareness of what has been learned. Sequence
learning is related to striatal dopamine levels, striatal activation, and
integrity of white matter connections. People with Parkinson's disease (PD) have
degeneration of dopamine-producing neurons, leading to dopamine deficiency and
therefore striatal deficits, and they have difficulties with sequencing,
including complex language comprehension and postural stability. Most research on
implicit sequence learning in PD has used motor-based tasks. However, because PD
presents with motor deficits, it is difficult to assess whether learning itself
is impaired in these tasks. The present study used an implicit sequence learning
task with a reduced motor component, the Triplets Learning Task (TLT). People
with PD and age- and education-matched healthy older adults completed three
sessions (each consisting of 10 blocks of 50 trials) of the TLT. Results revealed
that the PD group was able to learn the sequence, however, when learning was
examined using a Half Blocks analysis (Nemeth et al., 2013), which compared
learning in the 1st 25/50 trials of all blocks to that in the 2nd 25/50 trials,
the PD group showed significantly less learning than Controls in the 2nd Half
Blocks, but not in the 1st. Nemeth et al. (2013) hypothesized that the 1st Half
Blocks involve recall and reactivation of the sequence learned, thus reflecting
hippocampal-dependent learning, while the 2nd Half Blocks involve proceduralized
behavior of learned sequences, reflecting striatal-based learning. The present
results suggest that the PD group had intact hippocampal-dependent implicit
sequence learning, but impaired striatal-dependent learning. Thus, sequencing
deficits in PD are likely due to striatal impairments, but other brain systems,
such as the hippocampus, may be able to partially compensate for striatal decline
to improve performance.
PMID- 25136304
TI - Digit forces bias sensorimotor transformations underlying control of fingertip
position.
AB - Humans are able to modulate digit forces as a function of position despite
changes in digit placement that might occur from trial to trial or when changing
grip type for object manipulation. Although this phenomenon is likely to rely on
sensing the position of the digits relative to each other and the object, the
underlying mechanisms remain unclear. To address this question, we asked subjects
(n = 30) to match perceived vertical distance between the center of pressure
(CoP) of the thumb and index finger pads (dy ) of the right hand ("reference"
hand) using the same hand ("test" hand). The digits of reference hand were
passively placed collinearly (dy = 0 mm). Subjects were then asked to exert
different combinations of normal and tangential digit forces (Fn and Ftan ,
respectively) using the reference hand and then match the memorized dy using the
test hand. The reference hand exerted Ftan of thumb and index finger in either
same or opposite direction. We hypothesized that, when the tangential forces of
the digits are produced in opposite directions, matching error (1) would be
biased toward the directions of the tangential forces; and (2) would be greater
when the remembered relative contact points are matched with negligible digit
force production. For the test hand, digit forces were either negligible (0.5-1
N, 0 +/- 0.25 N; Experiment 1) or the same as those exerted by the reference hand
(Experiment 2).Matching error was biased towards the direction of digit
tangential forces: thumb CoP was placed higher than the index finger CoP when
thumb and index finger Ftan were directed upward and downward, respectively, and
vice versa (p < 0.001). However, matching error was not dependent on whether the
reference and test hand exerted similar or different forces. We propose that the
expected sensory consequence of motor commands for tangential forces in opposite
directions overrides estimation of fingertip position through haptic sensory
feedback.
PMID- 25136306
TI - Physical and neural entrainment to rhythm: human sensorimotor coordination across
tasks and effector systems.
AB - The human sensorimotor system can be readily entrained to environmental rhythms,
through multiple sensory modalities. In this review, we provide an overview of
theories of timekeeping that make this neuroentrainment possible. First, we
present recent evidence that contests the assumptions made in classic timekeeper
models. The role of state estimation, sensory feedback and movement parameters on
the organization of sensorimotor timing are discussed in the context of recent
experiments that examined simultaneous timing and force control. This discussion
is extended to the study of coordinated multi-effector movements and how they may
be entrained.
PMID- 25136307
TI - Subliminal cues bias perception of facial affect in patients with social phobia:
evidence for enhanced unconscious threat processing.
AB - Socially anxious individuals have been shown to exhibit altered processing of
facial affect, especially expressions signaling threat. Enhanced unaware
processing has been suggested an important mechanism which may give rise to
anxious conscious cognition and behavior. This study investigated whether
individuals with social anxiety disorder (SAD) are perceptually more vulnerable
to the biasing effects of subliminal threat cues compared to healthy controls. In
a perceptual judgment task, 23 SAD and 23 matched control participants were asked
to rate the affective valence of parametrically manipulated affective expressions
ranging from neutral to angry. Each trial was preceded by subliminal presentation
of an angry/neutral cue. The SAD group tended to rate target faces as "angry"
when the preceding subliminal stimulus was angry vs. neutral, while healthy
participants were not biased by the subliminal stimulus presentation. The
perceptual bias in SAD was also associated with higher reaction time latencies in
the subliminal angry cue condition. The results provide further support for
enhanced unconscious threat processing in SAD individuals. The implications for
etiology, maintenance, and treatment of SAD are discussed.
PMID- 25136305
TI - The influence of expertise on brain activation of the action observation network
during anticipation of tennis and volleyball serves.
AB - In many daily activities, and especially in sport, it is necessary to predict the
effects of others' actions in order to initiate appropriate responses. Recently,
researchers have suggested that the action-observation network (AON) including
the cerebellum plays an essential role during such anticipation, particularly in
sport expert performers. In the present study, we examined the influence of task
specific expertise on the AON by investigating differences between two expert
groups trained in different sports while anticipating action effects. Altogether,
15 tennis and 16 volleyball experts anticipated the direction of observed tennis
and volleyball serves while undergoing functional magnetic resonance imaging
(fMRI). The expert group in each sport acted as novice controls in the other
sport with which they had only little experience. When contrasting anticipation
in both expertise conditions with the corresponding untrained sport, a stronger
activation of AON areas (SPL, SMA), and particularly of cerebellar structures,
was observed. Furthermore, the neural activation within the cerebellum and the
SPL was linearly correlated with participant's anticipation performance,
irrespective of the specific expertise. For the SPL, this relationship also holds
when an expert performs a domain-specific anticipation task. Notably, the
stronger activation of the cerebellum as well as of the SMA and the SPL in the
expertise conditions suggests that experts rely on their more fine-tuned
perceptual-motor representations that have improved during years of training when
anticipating the effects of others' actions in their preferred sport. The
association of activation within the SPL and the cerebellum with the task
achievement suggests that these areas are the predominant brain sites involved in
fast motor predictions. The SPL reflects the processing of domain-specific
contextual information and the cerebellum the usage of a predictive internal
model to solve the anticipation task.
PMID- 25136308
TI - Own-race and own-age biases facilitate visual awareness of faces under
interocular suppression.
AB - The detection of a face in a visual scene is the first stage in the face
processing hierarchy. Although all subsequent, more elaborate face processing
depends on the initial detection of a face, surprisingly little is known about
the perceptual mechanisms underlying face detection. Recent evidence suggests
that relatively hard-wired face detection mechanisms are broadly tuned to all
face-like visual patterns as long as they respect the typical spatial
configuration of the eyes above the mouth. Here, we qualify this notion by
showing that face detection mechanisms are also sensitive to face shape and
facial surface reflectance properties. We used continuous flash suppression (CFS)
to render faces invisible at the beginning of a trial and measured the time
upright and inverted faces needed to break into awareness. Young Caucasian adult
observers were presented with faces from their own race or from another race
(race experiment) and with faces from their own age group or from another age
group (age experiment). Faces matching the observers' own race and age group were
detected more quickly. Moreover, the advantage of upright over inverted faces in
overcoming CFS, i.e., the face inversion effect (FIE), was larger for own-race
and own-age faces. These results demonstrate that differences in face shape and
surface reflectance influence access to awareness and configural face processing
at the initial detection stage. Although we did not collect data from observers
of another race or age group, these findings are a first indication that face
detection mechanisms are shaped by visual experience with faces from one's own
social group. Such experience-based fine-tuning of face detection mechanisms may
equip in-group faces with a competitive advantage for access to conscious
awareness.
PMID- 25136309
TI - The role of literal meaning in figurative language comprehension: evidence from
masked priming ERP.
AB - The role of literal meaning during the construction of meaning that goes beyond
pure literal composition was investigated by combining cross-modal masked priming
and ERPs. This experimental design was chosen to compare two conflicting
theoretical positions on this topic. The indirect access account claims that
literal aspects are processed first, and additional meaning components are
computed only if no satisfactory interpretation is reached. In contrast, the
direct access approach argues that figurative aspects can be accessed
immediately. We presented metaphors (These lawyers are hyenas, Experiment 1a and
1b) and producer-for-product metonymies (The boy read Boll, Experiment 2a and 2b)
with and without a prime word that was semantically relevant to the literal
meaning of the target word (furry and talented, respectively). In the
presentation without priming, metaphors revealed a biphasic N400-Late Positivity
pattern, while metonymies showed an N400 only. We interpret the findings within a
two-phase language architecture where contextual expectations guide initial
access (N400) and precede pragmatic adjustment resulting in reconceptualization
(Late Positivity). With masked priming, the N400-difference was reduced for
metaphors and vanished for metonymies. This speaks against the direct access view
that predicts a facilitating effect for the literal condition only and hence
would predict the N400-difference to increase. The results are more consistent
with indirect access accounts that argue for facilitation effects for both
conditions and consequently for consistent or even smaller N400-amplitude
differences. This combined masked priming ERP paradigm therefore yields new
insights into the role of literal meaning in the online composition of figurative
language.
PMID- 25136310
TI - Devaluation and sequential decisions: linking goal-directed and model-based
behavior.
AB - In experimental psychology different experiments have been developed to assess
goal-directed as compared to habitual control over instrumental decisions.
Similar to animal studies selective devaluation procedures have been used. More
recently sequential decision-making tasks have been designed to assess the degree
of goal-directed vs. habitual choice behavior in terms of an influential
computational theory of model-based compared to model-free behavioral control. As
recently suggested, different measurements are thought to reflect the same
construct. Yet, there has been no attempt to directly assess the construct
validity of these different measurements. In the present study, we used a
devaluation paradigm and a sequential decision-making task to address this
question of construct validity in a sample of 18 healthy male human participants.
Correlational analysis revealed a positive association between model-based
choices during sequential decisions and goal-directed behavior after devaluation
suggesting a single framework underlying both operationalizations and speaking in
favor of construct validity of both measurement approaches. Up to now, this has
been merely assumed but never been directly tested in humans.
PMID- 25136312
TI - Efficient foot motor control by Neymar's brain.
AB - How very long-term (over many years) motor skill training shapes internal motor
representation remains poorly understood. We provide valuable evidence that the
football brain of Neymar da Silva Santos Junior (the Brasilian footballer)
recruits very limited neural resources in the motor-cortical foot regions during
foot movements. We scanned his brain activity with a 3-tesla functional magnetic
resonance imaging (fMRI) while he rotated his right ankle at 1 Hz. We also
scanned brain activity when three other age-controlled professional footballers,
two top-athlete swimmers and one amateur footballer performed the identical task.
A comparison was made between Neymar's brain activity with that obtained from the
others. We found activations in the left medial-wall foot motor regions during
the foot movements consistently across all participants. However, the size and
intensity of medial-wall activity was smaller in the four professional
footballers than in the three other participants, despite no difference in amount
of foot movement. Surprisingly, the reduced recruitment of medial-wall foot motor
regions became apparent in Neymar. His medial-wall activity was smallest among
all participants with absolutely no difference in amount of foot movement. Neymar
may efficiently control given foot movements probably by largely conserving motor
cortical neural resources. We discuss this possibility in terms of over-years
motor skill training effect, use-dependent plasticity, and efficient motor
control.
PMID- 25136311
TI - Functional MRI activation in white matter during the Symbol Digit Modalities
Test.
AB - BACKGROUND: Recent evidence shows that functional magnetic resonance imaging
(fMRI) can detect activation in white matter (WM). Such advances have important
implications for understanding WM dysfunction. A key step in linking neuroimaging
advances to the evaluation of clinical disorders is to examine whether WM
activation can be detected at the individual level during clinical tests
associated with WM function. We used an adapted Symbol Digit Modalities Test
(SDMT) in a 4T fMRI study of healthy adults. RESULTS: RESULTS from 17 healthy
individuals revealed WM activation in 88% of participants (15/17). The activation
was in either the corpus callosum (anterior and/or posterior) or internal capsule
(left and/or right). CONCLUSIONS: The findings link advances in fMRI to an
established clinical test of WM function. Future work should focus on evaluating
patients with WM dysfunction.
PMID- 25136313
TI - From neuronal populations to behavior: a computational journey.
PMID- 25136314
TI - Depth information in natural environments derived from optic flow by insect
motion detection system: a model analysis.
AB - Knowing the depth structure of the environment is crucial for moving animals in
many behavioral contexts, such as collision avoidance, targeting objects, or
spatial navigation. An important source of depth information is motion parallax.
This powerful cue is generated on the eyes during translatory self-motion with
the retinal images of nearby objects moving faster than those of distant ones. To
investigate how the visual motion pathway represents motion-based depth
information we analyzed its responses to image sequences recorded in natural
cluttered environments with a wide range of depth structures. The analysis was
done on the basis of an experimentally validated model of the visual motion
pathway of insects, with its core elements being correlation-type elementary
motion detectors (EMDs). It is the key result of our analysis that the absolute
EMD responses, i.e., the motion energy profile, represent the contrast-weighted
nearness of environmental structures during translatory self-motion at a roughly
constant velocity. In other words, the output of the EMD array highlights
contours of nearby objects. This conclusion is largely independent of the scale
over which EMDs are spatially pooled and was corroborated by scrutinizing the
motion energy profile after eliminating the depth structure from the natural
image sequences. Hence, the well-established dependence of correlation-type EMDs
on both velocity and textural properties of motion stimuli appears to be
advantageous for representing behaviorally relevant information about the
environment in a computationally parsimonious way.
PMID- 25136315
TI - Resistive and reactive changes to the impedance of intracortical microelectrodes
can be mitigated with polyethylene glycol under acute in vitro and in vivo
settings.
AB - The reactive response of brain tissue to implantable intracortical
microelectrodes is thought to negatively affect their recordable signal quality
and impedance, resulting in unreliable longitudinal performance. The relationship
between the progression of the reactive tissue into a glial scar and the decline
in device performance is unclear. We show that exposure to a model protein
solution in vitro and acute implantation result in both resistive and capacitive
changes to electrode impedance, rather than purely resistive changes. We also
show that applying 4000 MW polyethylene glycol (PEG) prevents impedance increases
in vitro, and reduces the percent change in impedance in vivo following
implantation. Our results highlight the importance of considering the
contributions of non-cellular components to the decline in neural microelectrode
performance, and present a proof of concept for using a simple dip-coated PEG
film to modulate changes in microelectrode impedance.
PMID- 25136316
TI - The generation of induced pluripotent stem cells for macular degeneration as a
drug screening platform: identification of curcumin as a protective agent for
retinal pigment epithelial cells against oxidative stress.
AB - Age-related macular degeneration (AMD) is one retinal aging process that may lead
to irreversible vision loss in the elderly. Its pathogenesis remains unclear, but
oxidative stress inducing retinal pigment epithelial (RPE) cells damage is
perhaps responsible for the aging sequence of retina and may play an important
role in macular degeneration. In this study, we have reprogrammed T cells from
patients with dry type AMD into induced pluripotent stem cells (iPSCs) via
integration-free episomal vectors and differentiated them into RPE cells that
were used as an expandable platform for investigating pathogenesis of the AMD and
in-vitro drug screening. These patient-derived RPEs with the AMD-associated
background (AMD-RPEs) exhibited reduced antioxidant ability, compared with normal
RPE cells. Among several screened candidate drugs, curcumin caused most
significant reduction of ROS in AMD-RPEs. Pre-treatment of curcumin protected
these AMD-RPEs from H2O2-induced cell death and also increased the cytoprotective
effect against the oxidative stress of H2O2 through the reduction of ROS levels.
In addition, curcumin with its versatile activities modulated the expression of
many oxidative stress-regulating genes such as PDGF, VEGF, IGFBP-2, HO1, SOD2,
and GPX1. Our findings indicated that the RPE cells derived from AMD patients
have decreased antioxidative defense, making RPE cells more susceptible to
oxidative damage and thereby leading to AMD formation. Curcumin represented an
ideal drug that can effectively restore the neuronal functions in AMD patient
derived RPE cells, rendering this drug an effective option for macular
degeneration therapy and an agent against aging-associated oxidative stress.
PMID- 25136317
TI - Subtype and regional-specific neuroinflammation in sporadic creutzfeldt-jakob
disease.
AB - The present study identifies deregulated cytokines and mediators of the immune
response in the frontal cortex and cerebellum of sporadic Creutzfeldt-Jakob
disease (sCJD) MM1 and VV2 subtypes compared to age-matched controls. Deregulated
genes include pro- and anti-inflammatory cytokines, toll-like receptors, colony
stimulating factors, cathepsins, members of the complement system, and members of
the integrin and CTL/CTLD family with particular regional and sCJD subtype
patterns. Analysis of cytokines and mediators at protein level shows expression
of selected molecules and receptors in neurons, in astrocytes, and/or in
microglia, thus suggesting interactions between neurons and glial cells, mainly
microglia, in the neuroinflammatory response in sCJD. Similar inflammatory
responses have been shown in the tg340 sCJD MM1 mice, revealing a progressive
deregulation of inflammatory mediators with disease progression. Yet,
inflammatory molecules involved are subjected to species differences in humans
and mice. Moreover, inflammatory-related cell signaling pathways NFkappaB/IKK and
JAK/STAT are activated in sCJD and sCJD MM1 mice. Together, the present
observations show a self-sustained complex inflammatory and inflammatory-related
responses occurring already at early clinical stages in animal model and
dramatically progressing at advanced stages of sCJD. Considering this scenario,
measures tailored to modulate (activate or inhibit) specific molecules could be
therapeutic options in CJD.
PMID- 25136318
TI - The pleural mesothelium in development and disease.
AB - The pleural mesothelium, derived from the embryonic mesoderm, is formed by a
metabolically active monolayer of cells that blanket the chest wall and lungs on
the parietal and visceral surfaces, respectively. The pleura and lungs are formed
as a result of an intricate relationship between the mesoderm and the endoderm
during development. Mesenchymal signaling pathways such as Wnt/B-catenin, Bmp4,
and sonic hedgehog appear to be quintessential for lung development. Pleural
Mesothelial Cells (PMCs) are known to express Wilms tumor-1 (Wt1) gene and in
lineage labeling studies of the developing embryo, PMCs were found to track into
the lung parenchyma and undergo mesothelial-mesenchymal transition (MMT) to form
alpha-smooth muscle actin (alpha-SMA)-positive cells of the mesenchyme and
vasculature. There is definite evidence that mesothelial cells can differentiate
and this seems to play an important role in pleural and parenchymal pathologies.
Mesothelial cells can differentiate into adipocytes, chondrocytes, and
osteoblasts; and have been shown to clonally generate fibroblasts and smooth
muscle cells in murine models. This supports the possibility that they may also
modulate lung injury-repair by re-activation of developmental programs in the
adult reflecting an altered recapitulation of development, with implications for
regenerative biology of the lung. In a mouse model of lung fibrosis using lineage
tracing studies, PMCs lost their polarity and cell-cell junctional complexes,
migrated into lung parenchyma, and underwent phenotypic transition into
myofibroblasts in response to the pro-fibrotic mediator, transforming growth
factor-beta1 (TGF-beta1). However, intra-pleural heme-oxygenase-1 (HO-1)
induction inhibited PMC migration after intra-tracheal fibrogenic injury. Intra
pleural fluorescein isothiocyanate labeled nanoparticles decorated with a surface
antibody to mesothelin, a surface marker of mesothelial cells, migrate into the
lung parenchyma with PMCs supporting a potential role for pleural based therapies
to modulate pleural mesothelial activation and parenchymal disease progression.
PMID- 25136319
TI - Congenital heart malformations induced by hemodynamic altering surgical
interventions.
AB - Embryonic heart formation results from a dynamic interplay between genetic and
environmental factors. Blood flow during early embryonic stages plays a critical
role in heart development, as interactions between flow and cardiac tissues
generate biomechanical forces that modulate cardiac growth and remodeling. Normal
hemodynamic conditions are essential for proper cardiac development, while
altered blood flow induced by surgical manipulations in animal models result in
heart defects similar to those seen in humans with congenital heart disease. This
review compares the altered hemodynamics, changes in tissue properties, and
cardiac defects reported after common surgical interventions that alter
hemodynamics in the early chick embryo, and shows that interventions produce a
wide spectrum of cardiac defects. Vitelline vein ligation and left atrial
ligation decrease blood pressure and flow; and outflow tract banding increases
blood pressure and flow velocities. These three surgical interventions result in
many of the same cardiac defects, which indicate that the altered hemodynamics
interfere with common looping, septation and valve formation processes that occur
after intervention and that shape the four-chambered heart. While many similar
defects develop after the interventions, the varying degrees of hemodynamic load
alteration among the three interventions also result in varying incidence and
severity of cardiac defects, indicating that the hemodynamic modulation of
cardiac developmental processes is strongly dependent on hemodynamic load.
PMID- 25136322
TI - Reentrant processing mediates object substitution masking: comment on Poder
(2013).
AB - Object-substitution masking (OSM) occurs when a target stimulus and a surrounding
mask are displayed briefly together, and the display then continues with the mask
alone. Target identification is accurate when the stimuli co-terminate but is
progressively impaired as the duration of the trailing mask is increased. In
reentrant accounts, OSM is said to arise from iterative exchanges between brain
regions connected by two-way pathways. In an alternative account, OSM is
explained on the basis of exclusively feed-forward processes, without recourse to
reentry. Here I show that the feed-forward account runs afoul of the extant
phenomenological, behavioral, brain-imaging, and electrophysiological evidence.
Further, the feed-forward assumption that masking occurs when attention finds a
degraded target is shown to be entirely ad hoc. In contrast, the evidence is
uniformly consistent with a reentrant-processing account of OSM.
PMID- 25136321
TI - Processing of sub- and supra-second intervals in the primate brain results from
the calibration of neuronal oscillators via sensory, motor, and feedback
processes.
AB - The processing of time intervals in the sub- to supra-second range by the brain
is critical for the interaction of primates with their surroundings in
activities, such as foraging and hunting. For an accurate processing of time
intervals by the brain, representation of physical time within neuronal circuits
is necessary. I propose that time dimension of the physical surrounding is
represented in the brain by different types of neuronal oscillators, generating
spikes or spike bursts at regular intervals. The proposed oscillators include the
pacemaker neurons, tonic inputs, and synchronized excitation and inhibition of
inter-connected neurons. Oscillators, which are built inside various circuits of
brain, help to form modular clocks, processing time intervals or other temporal
characteristics specific to functions of a circuit. Relative or absolute duration
is represented within neuronal oscillators by "neural temporal unit," defined as
the interval between regularly occurring spikes or spike bursts. Oscillator
output is processed to produce changes in activities of neurons, named frequency
modulator neuron, wired within a separate module, represented by the rate of
change in frequency, and frequency of activities, proposed to encode time
intervals. Inbuilt oscillators are calibrated by (a) feedback processes, (b)
input of time intervals resulting from rhythmic external sensory stimulation, and
(c) synchronous effects of feedback processes and evoked sensory activity. A
single active clock is proposed per circuit, which is calibrated by one or more
mechanisms. Multiple calibration mechanisms, inbuilt oscillators, and the
presence of modular connections prevent a complete loss of interval timing
functions of the brain.
PMID- 25136323
TI - Embodied niche construction in the hominin lineage: semiotic structure and
sustained attention in human embodied cognition.
AB - Human evolution unfolded through a rather distinctive, dynamically constructed
ecological niche. The human niche is not only generally terrestrial in habitat,
while being flexibly and extensively heterotrophic in food-web connections. It is
also defined by semiotically structured and structuring embodied cognitive
interfaces, connecting the individual organism with the wider environment. The
embodied dimensions of niche-population co-evolution have long involved semiotic
system construction, which I hypothesize to be an evolutionarily primitive aspect
of learning and higher-level cognitive integration and attention in the great
apes and humans alike. A clearly pre-linguistic form of semiotic cognitive
structuration is suggested to involve recursively learned and constructed object
icons. Higher-level cognitive iconic representation of visually, auditorily, or
haptically perceived extrasomatic objects would be learned and evoked through
indexical connections to proprioceptive and affective somatic states. Thus,
private cognitive signs would be defined, not only by their learned and perceived
extrasomatic referents, but also by their associations to iconically represented
somatic states. This evolutionary modification of animal associative learning is
suggested to be adaptive in ecological niches occupied by long-lived, large
bodied ape species, facilitating memory construction and recall in highly varied
foraging and social contexts, while sustaining selective attention during goal
directed behavioral sequences. The embodied niche construction (ENC) hypothesis
of human evolution posits that in the early hominin lineage, natural selection
further modified the ancestral ape semiotic adaptations, favoring the recursive
structuration of concise iconic narratives of embodied interaction with the
environment.
PMID- 25136324
TI - Mindfulness-Based Functional Therapy: a preliminary open trial of an integrated
model of care for people with persistent low back pain.
AB - OBJECTIVES: This pilot study investigated the feasibility and clinical utility of
implementing a novel, evidence-informed, interdisciplinary group intervention
Mindfulness Based Functional Therapy (MBFT)-for the management of persistent low
back pain (LBP) in primary care. MBFT aimed to improve physical and psychological
functioning in patients with persistent LBP. DESIGN: A single-group repeated
measures design was utilized to gather data about feasibility, effect sizes,
clinically significant changes and patient satisfaction. SETTING: A community
sample of 16 adults (75% female), mean (SD) age 47.00 (9.12) years (range 26-65
years), with mean (SD) LBP duration of 8.00 (9.00) years participated, using a
simulated primary care setting at Curtin University in Australia. INTERVENTION:
MBFT is an 8-week group intervention co-facilitated by psychology and
physiotherapy disciplines. Content includes: mindfulness meditation training,
cognitive-functional physiotherapeutic movement retraining, pain education, and
group support. MAIN OUTCOME MEASURES: Several validated self-report measures were
used to assess functional disability, emotional functioning, mindfulness, pain
catastrophizing, health-related quality of life at baseline, post-intervention,
and 6 months follow-up. RESULTS: Adherence and satisfaction was high, with 85% of
participants highly satisfied with MBFT. Clinical significance analysis and
effect size estimates showed improvements in a number of variables, including
pain catastrophizing, physical functioning, role limitations due to physical
condition, and depression, although these may have occurred due to non
intervention effects. CONCLUSIONS: MBFT is feasible to implement in primary care.
Preliminary findings suggest that a randomized controlled trial is warranted to
investigate its efficacy in improving physical and emotional functioning in
people with disabling persistent LBP.
PMID- 25136320
TI - Gene * Environment interactions in autism spectrum disorders: role of epigenetic
mechanisms.
AB - Several studies support currently the hypothesis that autism etiology is based on
a polygenic and epistatic model. However, despite advances in epidemiological,
molecular and clinical genetics, the genetic risk factors remain difficult to
identify, with the exception of a few chromosomal disorders and several single
gene disorders associated with an increased risk for autism. Furthermore, several
studies suggest a role of environmental factors in autism spectrum disorders
(ASD). First, arguments for a genetic contribution to autism, based on updated
family and twin studies, are examined. Second, a review of possible prenatal,
perinatal, and postnatal environmental risk factors for ASD are presented. Then,
the hypotheses are discussed concerning the underlying mechanisms related to a
role of environmental factors in the development of ASD in association with
genetic factors. In particular, epigenetics as a candidate biological mechanism
for gene * environment interactions is considered and the possible role of
epigenetic mechanisms reported in genetic disorders associated with ASD is
discussed. Furthermore, the example of in utero exposure to valproate provides a
good illustration of epigenetic mechanisms involved in ASD and innovative
therapeutic strategies. Epigenetic remodeling by environmental factors opens new
perspectives for a better understanding, prevention, and early therapeutic
intervention of ASD.
PMID- 25136326
TI - Proximity and gaze influences facial temperature: a thermal infrared imaging
study.
AB - Direct gaze and interpersonal proximity are known to lead to changes in psycho
physiology, behavior and brain function. We know little, however, about subtler
facial reactions such as rise and fall in temperature, which may be sensitive to
contextual effects and functional in social interactions. Using thermal infrared
imaging cameras 18 female adult participants were filmed at two interpersonal
distances (intimate and social) and two gaze conditions (averted and direct). The
order of variation in distance was counterbalanced: half the participants
experienced a female experimenter's gaze at the social distance first before the
intimate distance (a socially "normal" order) and half experienced the intimate
distance first and then the social distance (an odd social order). At both
distances averted gaze always preceded direct gaze. We found strong correlations
in thermal changes between six areas of the face (forehead, chin, cheeks, nose,
maxilliary, and periorbital regions) for all experimental conditions and
developed a composite measure of thermal shifts for all analyses. Interpersonal
proximity led to a thermal rise, but only in the "normal" social order. Direct
gaze, compared to averted gaze, led to a thermal increase at both distances with
a stronger effect at intimate distance, in both orders of distance variation.
Participants reported direct gaze as more intrusive than averted gaze, especially
at the intimate distance. These results demonstrate the powerful effects of
another person's gaze on psycho-physiological responses, even at a distance and
independent of context.
PMID- 25136327
TI - Understanding social engagement in autism: being different in perceiving and
sharing affordances.
AB - In the current paper I will argue that the notion of affordances offers an
alternative to theory of mind (ToM) approaches in studying social engagement in
general and in explaining social engagement in autism spectrum disorder (ASD)
specifically. Affordances are the possibilities for action offered by the
environment. In contrast to ToM approaches, the concept of affordances implies
the complementarity of person and environment and rejects the dualism of mind and
behavior. In line with the Gibsonian idea that a child must eventually perceive
the affordances of the environment for others as well for herself in order to
become socialized, I will hypothesize that individuals with ASD often do not
perceive the same affordances in the environment as other people do and have
difficulties perceiving others' affordances. This can lead to a disruption of
interpersonal behaviors. I will further argue that the methods for studying
social engagement should be adapted if we want to take interaction into account.
PMID- 25136325
TI - A bihemispheric autonomic model for traumatic stress effects on health and
behavior.
AB - A bihemispheric autonomic model (BHAM) may support advanced understanding of
traumatic stress effects on physiology and behavior. The model builds on
established data showing hemispheric lateralization in management of the
autonomic nervous system, and proposes that traumatic stress can produce dominant
asymmetry in activity of bilateral homologous brain regions responsible for
autonomic management. Rightward and leftward dominant asymmetries are associated
with sympathetic high arousal or parasympathetic freeze tendencies, respectively,
and return to relative symmetry is associated with improved autonomic regulation.
Autonomic auto-calibration for recovery (inverse of Jacksonian dissolution
proposed by polyvagal theory) has implications for risk behaviors associated with
traumatic life stress. Trauma-induced high arousal may be associated with risk
for maladaptive behaviors to attenuate arousal (including abuse of alcohol or
sedative-hypnotics). Trauma-induced freeze mode (including callous-unemotional
trait) may be associated with low resting heart rate and risk for conduct
disorders. The model may explain higher prevalence of leftward hemispheric
abnormalities reported in studies of violence. Implications of the BHAM are
illustrated through case examples of a military special operations officer with
history of traumatic brain injury and post-traumatic stress disorder, and a
university student with persisting post-concussion symptoms. Both undertook use
of a noninvasive closed-loop neurotechnology - high-resolution, relational,
resonance-based, electroencephalic mirroring - with ensuing decrease in
hemispheric asymmetry, improvement in heart rate variability, and symptom
reduction. Finally, the BHAM aligns with calls for researchers to use brain
behavioral constructs (research domain criteria or RDoC, proposed by the National
Institutes of Mental Health) as building blocks for assessment and intervention
in mental health science.
PMID- 25136328
TI - Prospection and emotional memory: how expectation affects emotional memory
formation following sleep and wake.
AB - Successful prospective memory is necessarily driven by an expectation that
encoded information will be relevant in the future, leading to its preferential
placement in memory storage. Like expectation, emotional salience is another type
of cue that benefits human memory formation. Although separate lines of research
suggest that both emotional information and information explicitly expected to be
important in the future benefit memory consolidation, it is unknown how
expectation affects the processing of emotional information and whether sleep,
which is known to maximize memory consolidation, plays a critical role. The
purpose of this study was to investigate how expectation would impact the
consolidation of emotionally salient content, and whether this impact would
differ across delays of sleep and wake. Participants encoded scenes containing an
emotionally charged negative or neutral foreground object placed on a plausible
neutral background. After encoding, half of the participants were informed they
would later be tested on the scenes (expected condition), while the other half
received no information about the test (unexpected condition). At recognition,
following a 12-h delay of sleep or wakefulness, the scene components (objects and
backgrounds) were presented separately and one at a time, and participants were
asked to determine if each component was old or new. Results revealed a greater
disparity for memory of negative objects over their paired neutral backgrounds
for both the sleep and wake groups when the memory test was expected compared to
when it was unexpected, while neutral memory remained unchanged. Analyzing each
group separately, the wake group showed a threefold increase in the magnitude of
this object/background trade-off for emotional scenes when the memory test was
expected compared to when it was unexpected, while those who slept performed
similarly across conditions. These results suggest that emotional salience and
expectation cues interact to benefit emotional memory consolidation during a
delay of wakefulness. The sleeping brain, however, may automatically tag
emotionally salient information as important, such that explicit instruction of
an upcoming memory test does not further improve memory performance.
PMID- 25136330
TI - Bone status in patients with epilepsy: relationship to markers of bone
remodeling.
AB - Patients with epilepsy and treated with antiepileptic drugs (AEDs) may develop
metabolic bone disease; however, the exact pathogenesis of bone loss with AEDs is
still unclear. Included were 75 adults with epilepsy (mean age: 31.90 +/- 5.62
years; duration of treatment with AEDs: 10.57 +/- 3.55 years) and 40 matched
healthy controls. Bone mineral content (BMC) and bone mineral densities (BMD) of
the femoral neck and lumbar spine were measured using dual-energy X-ray
absorptiometry (DEXA). Blood samples were analyzed for calcium, magnesium,
phosphate, alkaline phosphatase (ALP), 25-hydroxy vitamin D (25OHD), soluble
receptor activator of nuclear factor-kappa B ligand (sRANKL), osteoprotegerin
(OPG), and OPG/RANKL ratio (markers of bone remodeling). Compared to controls,
patients had lower BMD, BMC, Z-score, and T-score at the femoral neck and lumbar
spine (all p < 0.001). Seventy-two percent and 29.33% of patients had
osteoporosis of the lumbar spine and femoral neck. Patients had significantly
lower serum calcium, 25(OH)D, and OPG and higher ALP, sRANKL levels, and
sRANKL/OPG (all p < 0.001). Fifty-two percent of patients had hypocalcemia, 93%
had hypovitaminosis D, 31% had high levels of sRANKL, and 49% had low levels of
OPG. No differences were identified between DEXA and laboratory results in
relation to the type, dose, or serum levels of AEDs. BMD at the femoral neck and
lumbar spine were found to be correlated with the duration of illness (p = 0.043;
p = 0.010), duration of treatment with AEDs (p < 0.001; p = 0.012), and serum
levels of 25(OH)D (p = 0.042; p = 0.010), sRANKLs (p = 0.005; p = 0.01), and OPG
(p = 0.006; p = 0.01). In linear regression analysis and after adjusting for
gender, age, weight, duration, and number of AEDs, we observed an association
between BMD, 25(OH)D (p = 0.04) and sRANKL (p = 0.03) concentrations. We conclude
that AEDs may compromise bone health through disturbance of mineral metabolism
and acceleration of bone turnover mechanisms.
PMID- 25136329
TI - The sleepy teenager - diagnostic challenges.
AB - The sleepy teenager puts the doctor in a, often tricky, situation where it must
be decided if we deal with normal physiology or if we should suspect pathological
conditions. What medical investigations are proper to consider? What differential
diagnoses should be considered in the first place? And what tools do we actually
have? The symptoms and problems that usually are presented at the clinical visit
can be both of medical and psychosocial character - and actually they are often a
mixture of both. Subsequently, the challenge to investigate the sleepy teenager
often includes the examination of a complex behavioral pattern. It is important
to train and develop diagnostic skills and to realize that the physiological or
pathological conditions that can cause the symptoms may have different
explanations. Research in sleep disorders has shown different pathological
mechanisms congruent with the variations in the clinical picture. There are
probably also different patterns of involved neuronal circuits although common
pathways may exist. The whole picture remains to be drawn in this interesting and
challenging area.
PMID- 25136331
TI - Brain Injury Markers: Where are We?
PMID- 25136332
TI - Ipsen 5i is a Novel Potent Pharmacoperone for Intracellularly Retained
Melanocortin-4 Receptor Mutants.
AB - Inactivating mutations of the melanocortin-4 receptor (MC4R) cause early-onset
severe obesity in humans. Comprehensive functional studies show that most of the
inactivating mutants of the MC4R are retained intracellularly. In the present
study, we investigated whether a small molecule inverse agonist of the MC4R,
Ipsen 5i, could act as a pharmacoperone and correct the cell surface expression
and function of intracellularly retained mutant MC4Rs using multiple cell lines,
including HEK293 and two neuronal cell lines. We showed that Ipsen 5i rescued the
cell surface expression of all 11 intracellularly retained mutant MC4Rs studied
herein in at least one cell line. Ipsen 5i functionally rescued seven mutants in
all cell lines used. One mutant (Y157S) was functionally rescued in HEK293 cells
but not in the two neuronal cell lines. Ipsen 5i increased cell surface
expression of three mutants (S58C, G98R, and F261S) but did not affect signaling.
Ipsen 5i had no effect on mutant MC4Rs with other defects (Delta88-92, D90N,
I102S) or no defect (N274S). It also did not affect trafficking of a misrouted
MC3R mutant (I335S). Cell impermeable peptide ligands of the MC4R or cell
permeable small molecule ligand of delta opioid receptor could not rescue
misrouted mutant MC4R. In summary, we demonstrated that Ipsen 5i was a novel
potent pharmacoperone of the MC4R, correcting trafficking and signaling of a
significant portion (73%) of intracellularly retained mutants. Additional studies
are needed to demonstrate its in vivo efficacy.
PMID- 25136333
TI - Comparative analysis of Salmonella susceptibility and tolerance to the biocide
chlorhexidine identifies a complex cellular defense network.
AB - Chlorhexidine is one of the most widely used biocides in health and agricultural
settings as well as in the modern food industry. It is a cationic biocide of the
biguanide class. Details of its mechanism of action are largely unknown. The
frequent use of chlorhexidine has been questioned recently, amidst concerns that
an overuse of this compound may select for bacteria displaying an altered
susceptibility to antimicrobials, including clinically important anti-bacterial
agents. We generated a Salmonella enterica serovar Typhimurium isolate
(ST24(CHX)) that exhibited a high-level tolerant phenotype to chlorhexidine,
following several rounds of in vitro selection, using sub-lethal concentrations
of the biocide. This mutant showed altered suceptibility to a panel of clinically
important antimicrobial compounds. Here we describe a genomic, transcriptomic,
proteomic, and phenotypic analysis of the chlorhexidine tolerant S. Typhimurium
compared with its isogenic sensitive progenitor. Results from this study describe
a chlorhexidine defense network that functions in both the reference
chlorhexidine sensitive isolate and the tolerant mutant. The defense network
involved multiple cell targets including those associated with the synthesis and
modification of the cell wall, the SOS response, virulence, and a shift in
cellular metabolism toward anoxic pathways, some of which were regulated by CreB
and Fur. In addition, results indicated that chlorhexidine tolerance was
associated with more extensive modifications of the same cellular processes
involved in this proposed network, as well as a divergent defense response
involving the up-regulation of additional targets such as the flagellar apparatus
and an altered cellular phosphate metabolism. These data show that sub-lethal
concentrations of chlorhexidine induce distinct changes in exposed Salmonella,
and our findings provide insights into the mechanisms of action and tolerance to
this biocidal agent.
PMID- 25136335
TI - Transposon-mediated directed mutation controlled by DNA binding proteins in
Escherichia coli.
PMID- 25136334
TI - Engineering processive DNA polymerases with maximum benefit at minimum cost.
AB - DNA polymerases need to be engineered to achieve optimal performance for
biotechnological applications, which often require high fidelity replication when
using modified nucleotides and when replicating difficult DNA sequences. These
tasks are achieved for the bacteriophage T4 DNA polymerase by replacing leucine
with methionine in the highly conserved Motif A sequence (L412M). The costs are
minimal. Although base substitution errors increase moderately, accuracy is
maintained for templates with mono- and dinucleotide repeats while replication
efficiency is enhanced. The L412M substitution increases intrinsic processivity
and addition of phage T4 clamp and single-stranded DNA binding proteins further
enhance the ability of the phage T4 L412M-DNA polymerase to replicate all types
of difficult DNA sequences. Increased pyrophosphorolysis is a drawback of
increased processivity, but pyrophosphorolysis is curbed by adding an inorganic
pyrophosphatase or divalent metal cations, Mn(2+) or Ca(2+). In the absence of
pyrophosphorolysis inhibitors, the T4 L412M-DNA polymerase catalyzed sequence
dependent pyrophosphorolysis under DNA sequencing conditions. The sequence
specificity of the pyrophosphorolysis reaction provides insights into how the T4
DNA polymerase switches between nucleotide incorporation, pyrophosphorolysis and
proofreading pathways. The L-to-M substitution was also tested in the yeast DNA
polymerases delta and alpha. Because the mutant DNA polymerases displayed similar
characteristics, we propose that amino acid substitutions in Motif A have the
potential to increase processivity and to enhance performance in biotechnological
applications. An underlying theme in this chapter is the use of genetic methods
to identify mutant DNA polymerases with potential for use in current and future
biotechnological applications.
PMID- 25136338
TI - A novel thermostable polymerase for RNA and DNA loop-mediated isothermal
amplification (LAMP).
AB - Meeting the goal of providing point of care (POC) tests for molecular detection
of pathogens in low resource settings places stringent demands on all aspects of
the technology. OmniAmp DNA polymerase (Pol) is a thermostable viral enzyme that
enables true POC use in clinics or in the field by overcoming important barriers
to isothermal amplification. In this paper, we describe the multiple advantages
of OmniAmp Pol as an isothermal amplification enzyme and provide examples of its
use in loop-mediated isothermal amplification (LAMP) for pathogen detection. The
inherent reverse transcriptase activity of OmniAmp Pol allows single enzyme
detection of RNA targets in RT-LAMP. Common methods of nucleic acid amplification
are highly susceptible to sample contaminants, necessitating elaborate nucleic
acid purification protocols that are incompatible with POC or field use. OmniAmp
Pol was found to be less inhibited by whole blood components typical in certain
crude sample preparations. Moreover, the thermostability of the enzyme compared
to alternative DNA polymerases (Bst) and reverse transcriptases allows
pretreatment of complete reaction mixes immediately prior to amplification, which
facilitates amplification of highly structured genome regions. Compared to Bst,
OmniAmp Pol has a faster time to result, particularly with more dilute templates.
Molecular diagnostics in field settings can be challenging due to the lack of
refrigeration. The stability of OmniAmp Pol is compatible with a dry format that
enables long term storage at ambient temperatures. A final requirement for field
operability is compatibility with either commonly available instruments or, in
other cases, a simple, inexpensive, portable detection mode requiring minimal
training or power. Detection of amplification products is shown using lateral
flow strips and analysis on a real-time PCR instrument. Results of this study
show that OmniAmp Pol is ideally suited for low resource molecular detection of
pathogens.
PMID- 25136336
TI - Same species, different diseases: how and why typhoidal and non-typhoidal
Salmonella enterica serovars differ.
AB - Human infections by the bacterial pathogen Salmonella enterica represent major
disease burdens worldwide. This highly ubiquitous species consists of more than
2600 different serovars that can be divided into typhoidal and non-typhoidal
Salmonella (NTS) serovars. Despite their genetic similarity, these two groups
elicit very different diseases and distinct immune responses in humans.
Comparative analyses of the genomes of multiple Salmonella serovars have begun to
explain the basis of the variation in disease manifestations. Recent advances in
modeling both enteric fever and intestinal gastroenteritis in mice will
facilitate investigation into both the bacterial- and host-mediated mechanisms
involved in salmonelloses. Understanding the genetic and molecular mechanisms
responsible for differences in disease outcome will augment our understanding of
Salmonella pathogenesis, host immunity, and the molecular basis of host
specificity. This review outlines the differences in epidemiology, clinical
manifestations, and the human immune response to typhoidal and NTS infections and
summarizes the current thinking on why these differences might exist.
PMID- 25136337
TI - Comparative proteome analysis reveals conserved and specific adaptation patterns
of Staphylococcus aureus after internalization by different types of human non
professional phagocytic host cells.
AB - Staphylococcus aureus is a human pathogen that can cause a wide range of
diseases. Although formerly regarded as extracellular pathogen, it has been shown
that S. aureus can also be internalized by host cells and persist within these
cells. In the present study, we comparatively analyzed survival and physiological
adaptation of S. aureus HG001 after internalization by two human lung epithelial
cell lines (S9 and A549), and human embryonic kidney cells (HEK 293). Combining
enrichment of bacteria from host-pathogen assays by cell sorting and quantitation
of the pathogen's proteome by mass spectrometry we characterized S. aureus
adaptation during the initial phase between 2.5 h and 6.5 h post-infection.
Starting with about 2 * 10(6) bacteria, roughly 1450 S. aureus proteins,
including virulence factors and metabolic enzymes were identified by spectral
comparison and classical database searches. Most of the bacterial adaptation
reactions, such as decreased levels of ribosomal proteins and metabolic enzymes
or increased amounts of proteins involved in arginine and lysine biosynthesis,
enzymes coding for terminal oxidases and stress responsive proteins or activation
of the sigma factor SigB were observed after internalization into any of the
three cell lines studied. However, differences were noted in central carbon
metabolism including regulation of fermentation and threonine degradation. Since
these differences coincided with different intracellular growth behavior,
complementary profiling of the metabolome of the different non-infected host cell
types was performed. This revealed similar levels of intracellular glucose but
host cell specific differences in the amounts of amino acids such as glycine,
threonine or glutamate. With this comparative study we provide an impression of
the common and specific features of the adaptation of S. aureus HG001 to specific
host cell environments as a starting point for follow-up studies with different
strain isolates and regulatory mutants.
PMID- 25136339
TI - Not just who, but how many: the importance of partner abundance in reef coral
symbioses.
AB - The performance and function of reef corals depends on the genetic identity of
their symbiotic algal partners, with some symbionts providing greater benefits
(e.g., photosynthate, thermotolerance) than others. However, these interaction
outcomes may also depend on partner abundance, with differences in the total
number of symbionts changing the net benefit to the coral host, depending on the
particular environmental conditions. We suggest that symbiont abundance is a
fundamental aspect of the dynamic interface between reef corals and the abiotic
environment that ultimately determines the benefits, costs, and functional
responses of these symbioses. This density-dependent framework suggests that
corals may regulate the size of their symbiont pool to match microhabitat
specific optima, which may contribute to the high spatiotemporal variability in
symbiont abundance observed within and among colonies and reefs. Differences in
symbiont standing stock may subsequently explain variation in energetics, growth,
reproduction, and stress susceptibility, and may mediate the impacts of
environmental change on these outcomes. However, the importance of symbiont
abundance has received relatively little recognition, possibly because commonly
used metrics based on surface area (e.g., symbiont cells cm(-2)) may be only
weakly linked to biological phenomena and are difficult to compare across
studies. We suggest that normalizing symbionts to biological host parameters,
such as units of protein or numbers of host cells, will more clearly elucidate
the functional role of symbiont abundance in reef coral symbioses. In this
article, we generate testable hypotheses regarding the importance of symbiont
abundance by first discussing different metrics and their potential links to
symbiosis performance and breakdown, and then describing how natural variability
and dynamics of symbiont communities may help explain ecological patterns on
coral reefs and predict responses to environmental change.
PMID- 25136341
TI - Trypanosoma cruzi-Host Cell Interaction.
PMID- 25136340
TI - Fold modulating function: bacterial toxins to functional amyloids.
AB - Many bacteria produce cytolytic toxins that target host cells or other competing
microbes. It is well known that environmental factors control toxin expression,
however, recent work suggests that some bacteria manipulate the fold of these
protein toxins to control their function. The beta-sheet rich amyloid fold is a
highly stable ordered aggregate that many toxins form in response to specific
environmental conditions. When in the amyloid state, toxins become inert, losing
the cytolytic activity they display in the soluble form. Emerging evidence
suggest that some amyloids function as toxin storage systems until they are again
needed, while other bacteria utilize amyloids as a structural matrix component of
biofilms. This amyloid matrix component facilitates resistance to biofilm
disruptive challenges. The bacterial amyloids discussed in this review reveal an
elegant system where changes in protein fold and solubility dictate the function
of proteins in response to the environment.
PMID- 25136343
TI - Extracellular vesicles as therapeutic tools in cardiovascular diseases.
AB - Extracellular vesicles (EVs), including microvesicles (MVs) and exosomes, are
small vesicles secreted from a wide variety of cells. Whereas MVs are particles
released by the outward budding of the plasma membrane, exosomes are derived from
endocytic compartments. Secretion of EVs can be enhanced by specific stimuli, and
increased plasma circulating levels of EVs have been correlated with
pathophysiological situations. MVs, already present in the blood of healthy
individuals, are considerably elevated in several cardiovascular diseases
associated with inflammation, suggesting that they can mediate deleterious
effects such as endothelial dysfunction or thrombosis. Nonetheless, very recent
studies also demonstrate that MVs may act as biological information vectors
transferring proteins or genetic material to maintain cell homeostasis, favor
cell repair, or even promote angiogenesis. Additionally, exosomes have also been
shown to have pro-angiogenic and cardio-protective properties. These beneficial
effects, therefore, reveal the potential therapeutical use of EVs in the field of
cardiovascular medicine and regenerative therapy. In this review, we will provide
an update of cellular processes modulated by EVs of specific interest in the
treatment of cardiovascular pathologies. A special focus will be made on the
morphogen sonic hedgehog (Shh) associated with EVs (EVs(Shh+)), which have been
shown to mediate many pro-angiogenic effects. In addition to offer a potential
source of cardiovascular markers, therapeutical potential of EVs reveal exciting
opportunities to deliver specific agents by non-immunogenic means to
cardiovascular system.
PMID- 25136344
TI - High atomic weight, high-energy radiation (HZE) induces transcriptional responses
shared with conventional stresses in addition to a core "DSB" response specific
to clastogenic treatments.
AB - Plants exhibit a robust transcriptional response to gamma radiation which
includes the induction of transcripts required for homologous recombination and
the suppression of transcripts that promote cell cycle progression. Various DNA
damaging agents induce different spectra of DNA damage as well as "collateral"
damage to other cellular components and therefore are not expected to provoke
identical responses by the cell. Here we study the effects of two different types
of ionizing radiation (IR) treatment, HZE (1 GeV Fe(26+) high mass, high charge,
and high energy relativistic particles) and gamma photons, on the transcriptome
of Arabidopsis thaliana seedlings. Both types of IR induce small clusters of
radicals that can result in the formation of double strand breaks (DSBs), but HZE
also produces linear arrays of extremely clustered damage. We performed these
experiments across a range of time points (1.5-24 h after irradiation) in both
wild-type plants and in mutants defective in the DSB-sensing protein kinase ATM.
The two types of IR exhibit a shared double strand break-repair-related damage
response, although they differ slightly in the timing, degree, and ATM-dependence
of the response. The ATM-dependent, DNA metabolism-related transcripts of the
"DSB response" were also induced by other DNA damaging agents, but were not
induced by conventional stresses. Both Gamma and HZE irradiation induced, at 24 h
post-irradiation, ATM-dependent transcripts associated with a variety of
conventional stresses; these were overrepresented for pathogen response, rather
than DNA metabolism. In contrast, only HZE-irradiated plants, at 1.5 h after
irradiation, exhibited an additional and very extensive transcriptional response,
shared with plants experiencing "extended night." This response was not apparent
in gamma-irradiated plants.
PMID- 25136345
TI - Divisions of labor in the thiamin biosynthetic pathway among organs of maize.
AB - The B vitamin thiamin is essential for central metabolism in all cellular
organisms including plants. While plants synthesize thiamin de novo, organs vary
widely in their capacities for thiamin synthesis. We use a transcriptomics
approach to appraise the distribution of de novo synthesis and thiamin salvage
pathways among organs of maize. We identify at least six developmental contexts
in which metabolically active, non-photosynthetic organs exhibit low expression
of one or both branches of the de novo thiamin biosynthetic pathway indicating a
dependence on inter-cellular transport of thiamin and/or thiamin precursors.
Neither the thiazole (THI4) nor pyrimidine (THIC) branches of the pathway are
expressed in developing pollen implying a dependence on import of thiamin from
surrounding floral and inflorescence organs. Consistent with that hypothesis,
organs of the male inflorescence and flowers are shown to have high relative
expression of the thiamin biosynthetic pathway and comparatively high thiamin
contents. By contrast, divergent patterns of THIC and THI4 expression occur in
the shoot apical meristem, embyro sac, embryo, endosperm, and root-tips
suggesting that these sink organs acquire significant amounts of thiamin via
salvage pathways. In the root and shoot meristems, expression of THIC in the
absence of THI4 indicates a capacity for thiamin synthesis via salvage of
thiazole, whereas the opposite pattern obtains in embryo and endosperm implying
that seed storage organs are poised for pyrimidine salvage. Finally, stable
isotope labeling experiments set an upper limit on the rate of de novo thiamin
biosynthesis in maize leaf explants. Overall, the observed patterns of thiamin
biosynthetic gene expression mirror the strategies for thiamin acquisition that
have evolved in bacteria.
PMID- 25136342
TI - Impaired clearance of apoptotic cells in chronic inflammatory diseases:
therapeutic implications.
AB - In healthy individuals, billions of cells die by apoptosis every day. Removal of
the dead cells by phagocytosis (a process called efferocytosis) must be efficient
to prevent secondary necrosis and the consequent release of pro-inflammatory cell
contents that damages the tissue environment and provokes autoimmunity. In
addition, detection and removal of apoptotic cells generally induces an anti
inflammatory response. As a consequence improper clearance of apoptotic cells,
being the result of either genetic anomalies and/or a persistent disease state,
contributes to the establishment and progression of a number of human chronic
inflammatory diseases such as autoimmune and neurological disorders, inflammatory
lung diseases, obesity, type 2 diabetes, or atherosclerosis. During the past
decade, our knowledge about the mechanism of efferocytosis has significantly
increased, providing therapeutic targets through which impaired phagocytosis of
apoptotic cells and the consequent inflammation could be influenced in these
diseases.
PMID- 25136346
TI - Capsicum chinensis L. growth and nutraceutical properties are enhanced by
biostimulants in a long-term period: chemical and metabolomic approaches.
AB - Two biostimulants, one derived from alfalfa plants (AH) and the other obtained
from red grape (RG), were chemically characterized using enzyme linked immuno
sorbent assays, Fourier transform infrared (FT-IR) and Raman spectroscopies. Two
doses (50 and 100 mL L(-1) for RG, and 25 and 50 mL L(-1) for AH) of
biostimulants were applied to Capsicum chinensis L. plants cultivated in pots
inside a tunnel. The experimental design consisted of the factorial combination
of treatment (no biostimulant, plus AH, plus RG) at three doses (zero, low, and
high) and two time-course applications (at the second and fourth week after
transplantation) and the effects were recorded at flowering and maturity. Both
biostimulants contained different amounts of indoleacetic acid and
isopentenyladenosine; the AH spectra exhibited amino acid functional groups in
the peptidic structure, while the RG spectra showed the presence of polyphenols,
such as resveratrol. These results revealed that at flowering, RG and AH
increased the weights of fresh leaves and fruits and the number of green fruits,
whereas at maturity, the biostimulants most affected the fresh weight and number
of red fruits. At flowering, the leaves of the treated plants contained high
amounts of epicatechin, ascorbic acid, quercetin, and dihydrocapsaicin. At
maturity, the leaves of the treated plants exhibited elevated amounts of
fructose, glucose, chlorogenic, and ferulic acids. Moreover, green fruits
exhibited a high content of chlorogenic acid, p-hydroxybenzoic acid, p-coumaric
acid and antioxidant activity, while both AH- and RG-treated red fruits were
highly endowed in capsaicin. The (1)H high-resolution magic-angle spinning
(HRMAS)-nuclear magnetic resonance (NMR) spectra of red fruits revealed that both
products induced a high amount of NADP(+), whereas RG also increased glucose,
fumarate, ascorbate, thymidine and high molecular weight species. Our results
suggested that AH and RG promoted plant growth and the production of secondary
metabolites, such as phenols.
PMID- 25136348
TI - Rec-8 dimorphism affects longevity, stress resistance and X-chromosome
nondisjunction in C. elegans, and replicative lifespan in S. cerevisiae.
AB - A quantitative trait locus (QTL) in the nematode C. elegans, "lsq4," was recently
implicated by mapping longevity genes. QTLs for lifespan and three stress
resistance traits coincided within a span of <300 kbp, later narrowed to <200
kbp. A single gene in this interval is now shown to modulate all lsq4-associated
traits. Full-genome analysis of transcript levels indicates that lsq4 contains a
dimorphic gene governing the expression of many sperm-specific genes, suggesting
an effect on spermatogenesis. Quantitative analysis of allele-specific
transcripts encoded within the lsq4 interval revealed significant, 2- to 15-fold
expression differences for 10 of 33 genes. Fourteen "dual-candidate" genes,
implicated by both position and expression, were tested for RNA-interference
effects on QTL-linked traits. In a strain carrying the shorter-lived allele,
knockdown of rec-8 (encoding a meiotic cohesin) reduced its transcripts 4-fold,
to a level similar to the longer-lived strain, while extending lifespan 25-26%,
whether begun before fertilization or at maturity. The short-lived lsq4 allele
also conferred sensitivity to oxidative and thermal stresses, and lower male
frequency (reflecting X-chromosome non-disjunction), traits reversed uniquely by
rec-8 knockdown. A strain bearing the longer-lived lsq4 allele, differing from
the short-lived strain at <0.3% of its genome, derived no lifespan or stress
survival benefit from rec-8 knockdown. We consider two possible explanations:
high rec-8 expression may include increased "leaky" expression in mitotic cells,
leading to deleterious destabilization of somatic genomes; or REC-8 may act
entirely in germ-line meiotic cells to reduce aberrations such as non
disjunction, thereby blunting a stress-resistance response mediated by innate
immunity. Replicative lifespan was extended 20% in haploid S. cerevisiae (BY4741)
by deletion of REC8, orthologous to nematode rec-8, implying that REC8 disruption
of mitotic-cell survival is widespread, exemplifying antagonistic pleiotropy
(opposing effects on lifespan vs. reproduction), and/or balancing selection
wherein genomic disruption increases genetic variation under harsh conditions.
PMID- 25136349
TI - The CNVrd2 package: measurement of copy number at complex loci using high
throughput sequencing data.
AB - Recent advances in high-throughout sequencing technologies have made it possible
to accurately assign copy number (CN) at CN variable loci. However, current
analytic methods often perform poorly in regions in which complex CN variation is
observed. Here we report the development of a read depth-based approach, CNVrd2,
for investigation of CN variation using high-throughput sequencing data. This
methodology was developed using data from the 1000 Genomes Project from the
CCL3L1 locus, and tested using data from the DEFB103A locus. In both cases,
samples were selected for which paralog ratio test data were also available for
comparison. The CNVrd2 method first uses observed read-count ratios to refine
segmentation results in one population. Then a linear regression model is applied
to adjust the results across multiple populations, in combination with a Bayesian
normal mixture model to cluster segmentation scores into groups for individual CN
counts. The performance of CNVrd2 was compared to that of two other read depth
based methods (CNVnator, cn.mops) at the CCL3L1 and DEFB103A loci. The highest
concordance with the paralog ratio test method was observed for CNVrd2
(77.8/90.4% for CNVrd2, 36.7/4.8% for cn.mops and 7.2/1% for CNVnator at CCL3L1
and DEF103A). CNVrd2 is available as an R package as part of the Bioconductor
project: http://www.bioconductor.org/packages/release/bioc/html/CNVrd2.html.
PMID- 25136347
TI - In silico analysis of protein Lys-N(??)-acetylation in plants.
AB - Among post-translational modifications, there are some conceptual similarities
between Lys-N(??)-acetylation and Ser/Thr/Tyr O-phosphorylation. Herein we
present a bioinformatics-based overview of reversible protein Lys-acetylation,
including some comparisons with reversible protein phosphorylation. The study of
Lys-acetylation of plant proteins has lagged behind studies of mammalian and
microbial cells; 1000s of acetylation sites have been identified in mammalian
proteins compared with only hundreds of sites in plant proteins. While most
previous emphasis was focused on post-translational modifications of histones,
more recent studies have addressed metabolic regulation. Being directly coupled
with cellular CoA/acetyl-CoA and NAD/NADH, reversible Lys-N(??)-acetylation has
the potential to control, or contribute to control, of primary metabolism,
signaling, and growth and development.
PMID- 25136350
TI - Simple, standardized incorporation of genetic risk into non-genetic risk
prediction tools for complex traits: coronary heart disease as an example.
AB - PURPOSE: Genetic risk assessment is becoming an important component of clinical
decision-making. Genetic Risk Scores (GRSs) allow the composite assessment of
genetic risk in complex traits. A technically and clinically pertinent question
is how to most easily and effectively combine a GRS with an assessment of
clinical risk derived from established non-genetic risk factors as well as to
clearly present this information to patient and health care providers. MATERIALS
AND METHODS: We illustrate a means to combine a GRS with an independent
assessment of clinical risk using a log-link function. We apply the method to the
prediction of coronary heart disease (CHD) in the Atherosclerosis Risk in
Communities (ARIC) cohort. We evaluate different constructions based on metrics
of effect change, discrimination, and calibration. RESULTS: The addition of a GRS
to a clinical risk score (CRS) improves both discrimination and calibration for
CHD in ARIC. RESULTS are similar regardless of whether external vs. internal
coefficients are used for the CRS, risk factor single nucleotide polymorphisms
(SNPs) are included in the GRS, or subjects with diabetes at baseline are
excluded. We outline how to report the construction and the performance of a GRS
using our method and illustrate a means to present genetic risk information to
subjects and/or their health care provider. CONCLUSION: The proposed method
facilitates the standardized incorporation of a GRS in risk assessment.
PMID- 25136351
TI - X-inactivation normalizes O-GlcNAc transferase levels and generates an O-GlcNAc
depleted Barr body.
AB - O-GlcNAc Transferase (OGT) catalyzes protein O-GlcNAcylation, an abundant and
dynamic nuclear and cytosolic modification linked to epigenetic regulation of
gene expression. The steady-state levels of O-GlcNAc are influenced by
extracellular glucose concentrations suggesting that O-GlcNAcylation may serve as
a metabolic sensor. Intriguingly, human OGT is located on the X-chromosome (Xq13)
close to the X-inactivation center (XIC), suggesting that OGT levels may be
controlled by dosage compensation. In human female cells, dosage compensation is
accomplished by X-inactivation. Long noncoding RNAs and polycomb repression act
together to produce an inactive X chromosome, or Barr body. Given that OGT has an
established role in polycomb repression, it is uniquely poised to auto-regulate
its own expression through X-inactivation. In this study, we examined OGT
expression in male, female and triple-X female human fibroblasts, which differ in
the number of inactive X chromosomes (Xi). We demonstrate that OGT is subjected
to random X-inactivation in normal female and triple X cells to regulate OGT RNA
levels. In addition, we used chromatin isolation by RNA purification (ChIRP) and
immunolocalization to examine O-GlcNAc levels in the Xi/Barr body. Despite the
established role of O-GlcNAc in polycomb repression, OGT and target proteins
bearing O-GlcNAc are largely depleted from the highly condensed Barr body. Thus,
while O-GlcNAc is abundantly present elsewhere in the nucleus, its absence from
the Barr body suggests that the transcriptional quiescence of the Xi does not
require OGT or O-GlcNAc.
PMID- 25136352
TI - History of the discovery of a master locus producing piRNAs: the flamenco/COM
locus in Drosophila melanogaster.
AB - The discovery of transposable elements (TEs) in the 1950s by B. McClintock
implied the existence of cellular regulatory systems controlling TE activity. The
discovery of flamenco (flam) an heterochromatic locus from Drosophila
melanogaster and its ability to survey several TEs such as gypsy, ZAM, and Idefix
contributed to peer deeply into the mechanisms of the genetic and epigenetic
regulation of TEs. flam was the first cluster producing small RNAs to be
discovered long before RNAi pathways were identified in 1998. As a result of the
detailed genetic analyses performed by certain laboratories and of the
sophisticated genetic tools they developed, this locus has played a major role in
our understanding of piRNA mediated TE repression in animals. Here we review the
first discovery of this locus and retrace decades of studies that led to our
current understanding of the relationship between genomes and their TE targets.
PMID- 25136354
TI - Viper bites complicate chronic agrochemical nephropathy in rural Sri Lanka.
AB - Snakebite is a common occupational health hazard among Sri Lankan agricultural
workers, particularly in the North Central Province. Viperine snakes, mainly
Russell's viper envenomation, frequently lead to acute renal failure. During the
last two decades, an agrochemical nephropathy, a chronic tubulointerstitial
disease has rapidly spread over this area leading to high morbidity and
mortality. Most of the epidemiological characteristics of these two conditions
overlap, increasing the chances of co-occurrence. Herein, we describe four
representative cases of viperine snakebites leading to variable clinical
presentations, in patients with chronic agrochemical nephropathy, including two
patients presented with acute and delayed anuria. These cases suggest the
possibility of unusual manifestations of snakebite in patients with Sri Lankan
agrochemical nephropathy, of which the clinicians should be aware. It could be
postulated that the existing scenario in the Central America could also lead to
similar clinical presentations.
PMID- 25136355
TI - Automated White Matter Hyperintensity Detection in Multiple Sclerosis Using 3D T2
FLAIR.
AB - White matter hyperintensities (WMH) seen on T2WI are a hallmark of multiple
sclerosis (MS) as it indicates inflammation associated with the disease.
Automatic detection of the WMH can be valuable in diagnosing and monitoring of
treatment effectiveness. T2 fluid attenuated inversion recovery (FLAIR) MR images
provided good contrast between the lesions and other tissue; however the signal
intensity of gray matter tissue was close to the lesions in FLAIR images that may
cause more false positives in the segment result. We developed and evaluated a
tool for automated WMH detection only using high resolution 3D T2 fluid
attenuated inversion recovery (FLAIR) MR images. We use a high spatial frequency
suppression method to reduce the gray matter area signal intensity. We evaluate
our method in 26 MS patients and 26 age matched health controls. The data from
the automated algorithm showed good agreement with that from the manual
segmentation. The linear correlation between these two approaches in comparing
WMH volumes was found to be Y = 1.04X + 1.74 (R (2) = 0.96). The automated
algorithm estimates the number, volume, and category of WMH.
PMID- 25136353
TI - Genetic factors and manganese-induced neurotoxicity.
AB - Manganese (Mn), is a trace metal required for normal physiological processes in
humans. Mn levels are tightly regulated, as high levels of Mn result in
accumulation in the brain and cause a neurological disease known as manganism.
Manganism shares many similarities with Parkinson's disease (PD), both at the
physiological level and the cellular level. Exposure to high Mn-containing
environments increases the risk of developing manganism. Mn is absorbed primarily
through the intestine and then released in the blood. Excessive Mn is secreted in
the bile and excreted in feces. Mn enters and exits cells through a number of non
specific importers localized on the cell membrane. Mutations in one of the Mn
exporters, SLC30A10 (solute carrier family 30, member 10), result in Mn induced
toxicity with liver impairments and neurological dysfunction. Four PD genes have
been identified in connection to regulation of Mn toxicity, shedding new light on
potential links between manganism and PD.
PMID- 25136358
TI - An ICT-Based Diabetes Management System Tested for Health Care Delivery in the
African Context.
AB - The demand for new healthcare services is growing rapidly. Improving
accessibility of the African population to diabetes care seems to be a big
challenge in most countries where the number of care centers and medical staff is
reduced. Information and communication technologies (ICT) have great potential to
address some of these challenges faced by several countries in providing
accessible, cost-effective, and high-quality health care services. This paper
presents the Mobil Diab system which is a telemedical approach proposed for the
management of long-term diseases. The system applies modern mobile and web
technologies which overcome geographical barriers, and increase access to health
care services. The idea of the system is to involve patients in the therapy
process and motivate them for an active participation. For validation of the
system in African context, a trial was conducted in the Democratic Republic of
Congo. 40 Subjects with diabetes divided randomly into control and intervention
groups were included in the test. Results show that Mobil Diab is suitable for
African countries and presents a number of benefits for the population and public
health care system. It improves clinical management and delivery of diabetes care
services by enhancing access, quality, motivation, reassurance, efficiency, and
cost-effectiveness.
PMID- 25136357
TI - Haematuria: an imaging guide.
AB - This paper discusses the current status of imaging in the investigation of
patients with haematuria. The physician must rationalize imaging so that serious
causes such as malignancy are promptly diagnosed while at the same time not
exposing patients to unnecessary investigations. There is currently no universal
agreement about the optimal imaging work up of haematuria. The choice of modality
to image the urinary tract will depend on individual patient factors such as age,
the presence of risk factors for malignancy, renal function, a history of
calculus disease and pregnancy, and other factors, such as local policy and
practice, cost effectiveness and availability of resources. The role of all
modalities, including conventional radiography, intravenous urography/excretory
urography, ultrasonography, retrograde pyelography, multidetector computed
tomography urography (MDCTU), and magnetic resonance urography, is discussed.
This paper highlights the pivotal role of MDCTU in the imaging of the patient
with haematuria and discusses issues specific to this modality including protocol
design, imaging of the urothelium, and radiation dose. Examination protocols
should be tailored to the patient while all the while optimizing radiation dose.
PMID- 25136356
TI - Targeting angiogenesis and tumor microenvironment in metastatic colorectal
cancer: role of aflibercept.
AB - In the last decades, we have progressively observed an improvement in therapeutic
options for metastatic colorectal cancer (mCRC) treatment with a progressive
prolongation of survival. mCRC prognosis still remains poor with low percentage
of 5-year survival. Targeted agents have improved results obtained with standard
chemotherapy. Angiogenesis plays a crucial role in colorectal cancer growth,
proliferation, and metastasization and it has been investigated as a potential
target for mCRC treatment. Accordingly, novel antiangiogenic targeted agents
bevacizumab, regorafenib, and aflibercept have been approved for mCRC treatment
as the result of several phase III randomized trials. The development of a tumor
permissive microenvironment via the aberrant expression by tumor cells of
paracrine factors alters the tumor-stroma interactions inducing an expansion of
proangiogenic signals. Recently, the VELOUR study showed that addition of
aflibercept to FOLFIRI regimen as a second-line therapy for mCRC improved
significantly OS, PFS, and RR. This molecule represents a valid second-line
therapeutic option and its peculiar ability to interfere with placental growth
factor (PlGF)/vascular endothelial growth factor receptor 1 (VEGFR1) axis makes
it effective in targeting angiogenesis, inflammatory cells and in overcoming
resistances to anti-angiogenic first-line treatment. Here, we discuss about
Aflibercept peculiar ability to interfere with tumor microenvironment and
angiogenic pathway.
PMID- 25136359
TI - Physical Activity, Physical Performance, and Biological Markers of Health among
Sedentary Older Latinos.
AB - Background. Physical activity is associated with better physical health, possibly
by changing biological markers of health such as waist circumference and
inflammation, but these relationships are unclear and even less understood among
older Latinos-a group with high rates of sedentary lifestyle. Methods.
Participants were 120 sedentary older Latino adults from senior centers.
Community-partnered research methods were used to recruit participants.
Inflammatory (C-reactive protein) and metabolic markers of health (waist
circumference, HDL-cholesterol, triglycerides, insulin, and glucose), physical
activity (Yale physical activity survey), and physical performance (short
physical performance NIA battery) were measured at baseline and 6-month followup.
Results. Eighty percent of the sample was female. In final adjusted cross
sectional models, better physical activity indices were associated with faster
gait speed (P < 0.05). In adjusted longitudinal analyses, change in self-reported
physical activity level correlated inversely with change in CRP (beta = -0.05; P
= 0.03) and change in waist circumference (beta = -0.16; P = 0.02). Biological
markers of health did not mediate the relationship between physical activity and
physical performance. Conclusion. In this community-partnered study, higher
physical activity was associated with better physical performance in cross
sectional analyses. In longitudinal analysis, increased physical activity was
associated with improvements in some metabolic and inflammatory markers of
health.
PMID- 25136360
TI - Chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by
methamphetamine.
AB - Methamphetamine intoxication can cause acute hepatic failure. Chlorogenic and
caftaric acids are the major dietary polyphenols present in various foods. The
aim of this study was to evaluate the protective role of chlorogenic and caftaric
acids in liver toxicity and oxidative stress induced by methamphetamine in rats.
Thirty-two male albino rats were divided into 4 equal groups. Group 1, which was
control group, was injected (i.p) with saline (1 mL/kg) twice a day over seven
day period. Groups 2, 3, and 4 were injected (i.p) with methamphetamine (10
mg/kg) twice a day over seven-day period, where groups 3 and 4 were injected
(i.p) with 60 mg/kg chlorogenic acid and 40 mg/kg caftaric acid, respectively,
one day before methamphetamine injections. Methamphetamine increased serum
aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase,
bilirubin, cholesterol, low-density lipoprotein, and triglycerides. Also,
malondialdehyde in serum, liver, and brain and plasma and liver nitric oxide
levels were increased while methamphetamine induced a significant decrease in
serum total protein, albumin, globulin, albumin/globulin ratio, brain serotonin,
norepinephrine and dopamine, blood and liver superoxide dismutase, and
glutathione peroxidase levels. Chlorogenic and caftaric acids prior to
methamphetamine injections restored all the above parameters to normal values. In
conclusion, chlorogenic and caftaric acids before methamphetamine injections
prevented liver toxicity and oxidative stress where chlorogenic acid was more
effective.
PMID- 25136361
TI - Micro- and Macroelemental Composition and Safety Evaluation of the Nutraceutical
Moringa oleifera Leaves.
AB - Moringa oleifera is a multipurpose plant used in Ghana and most parts of Africa.
Its high mineral, protein, and vitamins content has enabled its use as a
nutraceutical and panacea for various diseases. This study aimed at measuring the
micro- and macroelements content of dried Moringa oleifera leaves using energy
dispersive X-ray fluorescence spectroscopic (EDXRF) and assessing its
toxicological effect in rats. Acute toxicity (5000 mg/kg) and a subacute toxicity
studies of the leaf (40 mg/kg to 1000 mg/kg) extract were conducted in rats.
Blood samples were assessed for biochemical and haematological parameters.
Results showed significant levels of thirty-five (35) elements (14 macroelements
and 21 microelements) in M. oleifera extract. There were no observed overt
adverse reactions in the acute and subacute studies. Although there were observed
elevations in liver enzymes ALT and ALP (P < 0.001) and lower creatinine levels
in the extract treated groups, no adverse histopathological findings were found.
Moringa oleifera dried leaf extract may, therefore, be reasonably safe for
consumption. However, the consumption of Moringa oleifera leaves should not
exceed a maximum of 70 grams per day to prevent cumulative toxicity of these
essential elements over long periods.
PMID- 25136362
TI - The TG/HDL-C Ratio Might Be a Surrogate for Insulin Resistance in Chinese
Nonobese Women.
AB - Obejective. To examine the discriminatory power of triglyceride (TG) and
triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) for insulin
resistance (IR) in a normoglycaemic Chinese population. Methods. The data were
collected from 711 individuals. The normoglycaemic individuals were eventually
included in the study (n = 533, age: 62.8 +/- 6.6 years, male: 56.8%), who were
with a fasting plasma glucose < 6.1 mmol/L and without a history of diabetes. IR
was defined as the upper quintile (>=1.6) of homeostasis model assessment of IR.
Area under the receiver operating characteristic curve (AROC) was used to examine
the discriminatory power. Results. The discriminatory power of TG/HDL-C for IR
was acceptable in women with a BMI < 24 kg/m(2) or waist circumference < 80 cm
(AROCs: 0.718 and 0.713, resp.); however, the discriminatory power was not
acceptable in the obese women. TG/HDL-C was not an acceptable marker of IR in
men. The discriminatory power of TG for IR was not acceptable in both men and
women. Conclusions. The discriminatory power of TG/HDL-C for IR differs by gender
and obesity index in the normoglycaemic Chinese population, and TG/HDL-C could
discriminate IR in the nonobese and normoglycaemic women.
PMID- 25136363
TI - Leptin effects on the regenerative capacity of human periodontal cells.
AB - Obesity is increasing throughout the globe and characterized by excess adipose
tissue, which represents a complex endocrine organ. Adipose tissue secrets
bioactive molecules called adipokines, which act at endocrine, paracrine, and
autocrine levels. Obesity has recently been shown to be associated with
periodontitis, a disease characterized by the irreversible destruction of the
tooth-supporting tissues, that is, periodontium, and also with compromised
periodontal healing. Although the underlying mechanisms for these associations
are not clear yet, increased levels of proinflammatory adipokines, such as
leptin, as found in obese individuals, might be a critical pathomechanistic link.
The objective of this study was to examine the impact of leptin on the
regenerative capacity of human periodontal ligament (PDL) cells and also to study
the local leptin production by these cells. Leptin caused a significant
downregulation of growth (TGFbeta1, and VEGFA) and transcription (RUNX2) factors
as well as matrix molecules (collagen, and periostin) and inhibited SMAD
signaling under regenerative conditions. Moreover, the local expression of leptin
and its full-length receptor was significantly downregulated by inflammatory,
microbial, and biomechanical signals. This study demonstrates that the hormone
leptin negatively interferes with the regenerative capacity of PDL cells,
suggesting leptin as a pathomechanistic link between obesity and compromised
periodontal healing.
PMID- 25136364
TI - Cannabinoid receptor 1 gene polymorphisms and nonalcoholic Fatty liver disease in
women with polycystic ovary syndrome and in healthy controls.
AB - Context. Polycystic ovary syndrome (PCOS) is frequently associated with
nonalcoholic fatty liver disease (NAFLD). The endocannabinoid system may play a
crucial role in the pathogenesis of NAFLD. Polymorphism of the cannabinoid
receptor 1 gene (CNR1) may be responsible for individual susceptibility to
obesity and related conditions. Objective. To determine the role of genetic
variants of CNR1 in the etiopathology of NAFLD in women with PCOS. Design and
Setting. Our department (a tertiary referral center) conducted a cross-sectional,
case-controlled study. Subjects. 173 women with PCOS (aged 20-35) and 125
healthy, age- and weight-matched controls were studied. Methods. Hepatic
steatosis was assessed by ultrasound evaluation. Single nucleotide polymorphisms
of CNR1 (rs806368, rs12720071, rs1049353, rs806381, rs10485170, rs6454674) were
genotyped. Results. Frequency of the G allele of rs806381 (P < 0.025) and the GG
genotype of rs10485170 (P < 0.03) was significantly higher in women with PCOS and
NAFLD than in PCOS women without NAFLD. Frequency of the TT genotype of rs6454674
was higher in PCOS women with NAFLD (not significantly, P = 0.059). In
multivariate stepwise regression, allele G of rs806381 was associated with PCOS +
NAFLD phenotype. Conclusion. Our preliminary results suggest the potential role
of CNR1 polymorphisms in the etiology of NAFLD, especially in PCOS women.
PMID- 25136366
TI - Association between Serum Uric Acid Level and Metabolic Syndrome and Its Sex
Difference in a Chinese Community Elderly Population.
AB - Objective. This study aimed to evaluate the association between serum uric acid
(SUA) levels within a normal to high range and the risk of metabolic syndrome
(MetS) among community elderly and explore the sex difference. Design and
Methods. A cross-sectional study was conducted in a representative urban area of
Beijing between 2009 and 2010. A two-stage stratified clustering sampling method
was used and 2102 elderly participants were included. Results. The prevalence of
hyperuricemia and MetS was 16.7% and 59.1%, respectively. There was a strong
association between hyperuricemia and four components of MetS in women and three
components in men. Multiple logistic regression analysis showed ORs of
hyperuricemia for MetS were 1.67 (95% CI: 1.11-2.50) in men and 2.73 (95% CI:
1.81-4.11) in women. Even in the normal range, the ORs for MetS increased
gradually according to SUA levels. MetS component number also showed an
increasing trend across SUA quartile in both sexes (P for trend < 0.01).
Conclusion. This study suggests that higher SUA levels, even in the normal range,
are positively associated with MetS among Chinese community elderly, and the
association is stronger in women than men. Physicians should recognize MetS as a
frequent comorbidity of hyperuricemia and take early action to prevent subsequent
disease burden.
PMID- 25136365
TI - Coronary Heart Disease in Postmenopausal Women with Type II Diabetes Mellitus and
the Impact of Estrogen Replacement Therapy: A Narrative Review.
AB - Coronary heart disease is the main cause of death in postmenopausal women (PMW);
moreover its mortality exceeds those for breast cancer in women at all ages. Type
II diabetes mellitus is a major cardiovascular risk factor and there is some
evidence that the risk conferred by diabetes is greater in women than in men. It
was established that the deficiency of endogenous estrogens promotes the
atherosclerosis process. However, the impact of estrogen replacement therapy
(ERT) on cardiovascular prevention remains controversial. Some authors strongly
recommend it, whereas others revealed a concerning trend toward harm. This review
tries to underlines the different components of cardiovascular risk in diabetic
PMW and to define the place of ERT.
PMID- 25136367
TI - The Need for Orthodontic Treatment among Vietnamese School Children and Young
Adults.
AB - Objective. The aim of this study was to evaluate the need for orthodontic
treatment among 12-year-old school children and 18-year-olds from Da Nang,
Vietnam. Basic Research Design. A random representative sample of 200 12-year-old
children from primary schools in Da Nang city was gathered. In addition, 200 18
year-old students were randomly selected from among the 4000 students studying at
Da Nang University of Medical Technology and Pharmacy, Vietnam. All the subjects
were evaluated according to Angle's molar relationship, the presence of
malocclusion, and the components of the Index of Orthodontic Treatment Need
(Dental Health Component, DHC, and Aesthetic Component, AC). Results. The DHC of
index of orthodontic treatment need (IOTN) for 12-year-olds was in 60% of cases
no or little, in 21% of cases moderate, and in 19% of cases definitive, while the
prevalence of moderate and definitive need for treatment among the 18-year-olds
was 24% and 30.5%, respectively. The prevalence of class III malocclusion,
contact point displacement, and crossbite was higher in 18-year-olds than among
the 12-year-olds, while the prevalence of increased overjet and increased
overbite had decreased in 18-year-olds compared to the group of 12-year-olds.
Conclusions. There is a strong need for orthodontic treatment in Vietnam's
population. The need for orthodontic treatment was determined by contact point
displacement, crossbite, increased overjet, and increased overbite.
PMID- 25136368
TI - Effect of recycling protocol on mechanical strength of used mini-implants.
AB - Purpose. This study evaluated the influence of recycling process on the torsional
strength of mini-implants. Materials and Methods. Two hundred mini-implants were
divided into 4 groups with 50 screws equally distributed in five diameters (1.3
to 1.7 mm): control group (CG): unused mini-implants, G1: mini-implants inserted
in pig iliac bone and removed, G2: same protocol of group 1 followed by
sonication for cleaning and autoclave sterilization, and G3: same insertion
protocol of group 1 followed by sonication for cleaning before and after
sandblasting (Al2O3-90 u) and autoclave sterilization. G2 and G3 mini-implants
were weighed after recycling process to evaluate weight loss (W). All the screws
were broken to determine the fracture torque (FT). The influence of recycling
process on FT and W was evaluated by ANOVA, Mann-Whitney, and multiple linear
regression analysis. Results. FT was not influenced by recycling protocols even
when sandblasting was added. Sandblasting caused weight loss due to abrasive
mechanical stripping of screw surface. Screw diameter was the only variable that
affected FT. Conclusions. Torsional strengths of screws that underwent the
recycling protocols were not changed. Thus, screw diameter choice can be a more
critical step to avoid screw fracture than recycling decision.
PMID- 25136370
TI - Efficacy of topical mesenchymal stem cell therapy in the treatment of
experimental dry eye syndrome model.
AB - Purpose. The current study was set out to address the therapeutic efficacy of
topically applied mesenchymal stem cells (MSCs) on dry eye syndrome (DES) induced
by benzalkonium chloride (BAC) in rats. Methods. Rats were divided into two
groups just after establishment of DES. Eye drops containing either
bromodeoxyuridine labeled MSCs (n = 9) or phosphate buffer solution (n = 7) were
topically applied once daily for one week. Schirmer test, break-up time score,
ocular surface evaluation tests, and corneal inflammatory index scoring tests
were applied to all rats at baseline and after treatment. All rats were
sacrificed after one week for histological and electron microscopic analysis.
Results. Mean aqueous tear volume and tear film stability were significantly
increased in rats treated with MSCs (P < 0.05). Infiltration of bromodeoxyuridine
labeled MSCs into the meibomian glands and conjunctival epithelium was observed
in MSCs treated rats. Increased number of secretory granules and number of goblet
cells were observed in MSCs treated rats. Conclusion. Topical application of MSCs
could be a safe and effective method for the treatment of DES and could
potentially be used for further clinical research studies.
PMID- 25136369
TI - Early prediction of preeclampsia.
AB - Effective screening for the development of early onset preeclampsia (PE) can be
provided in the first-trimester of pregnancy. Screening by a combination of
maternal risk factors, uterine artery Doppler, mean arterial pressure, maternal
serum pregnancy-associated plasma protein-A, and placental growth factor can
identify about 95% of cases of early onset PE for a false-positive rate of 10%.
PMID- 25136371
TI - Determination of lead, cations, and anions concentration in indoor and outdoor
air at the primary schools in Kuala Lumpur.
AB - This study was carried out to determine the concentration of lead (Pb), anions,
and cations at six primary schools located around Kuala Lumpur. Low volume
sampler (MiniVol PM10) was used to collect the suspended particulates in indoor
and outdoor air. Results showed that the concentration of Pb in indoor air was in
the range of 5.18 +/- 1.08 MUg/g-7.01 +/- 0.08 MUg/g. All the concentrations of
Pb in indoor air were higher than in outdoor air at all sampling stations. The
concentrations of cations and anions were higher in outdoor air than in indoor
air. The concentration of Ca(2+) (39.51 +/- 5.01 mg/g-65.13 +/- 9.42 mg/g) was
the highest because the cation existed naturally in soil dusts, while the
concentrations of NO3 (-) and SO4 (2-) were higher in outdoor air because there
were more sources of exposure for anions in outdoor air, such as highly congested
traffic and motor vehicles emissions. In comparison, the concentration of NO3 (-)
(29.72 +/- 0.31 MUg/g-32.00 +/- 0.75 MUg/g) was slightly higher than SO4 (2-).
The concentrations of most of the parameters in this study, such as Mg(2+),
Ca(2+), NO3 (-), SO4 (2-), and Pb(2+), were higher in outdoor air than in indoor
air at all sampling stations.
PMID- 25136372
TI - Treatment of acute lymphoblastic leukemia from traditional chinese medicine.
AB - Acute lymphoblastic leukemia (ALL) is a cancer that immature white blood cells
continuously overproduce in the bone marrow. These cells crowd out normal cells
in the bone marrow bringing damage and death. Methotrexate (MTX) is a drug used
in the treatment of various cancer and autoimmune diseases. In particular, for
the treatment of childhood acute lymphoblastic leukemia, it had significant
effect. MTX competitively inhibits dihydrofolate reductase (DHFR), an enzyme that
participates in the tetrahydrofolate synthesis so as to inhibit purine synthesis.
In addition, its downstream metabolite methotrexate polyglutamates (MTX-PGs)
inhibit the thymidylate synthase (TS). Therefore, MTX can inhibit the synthesis
of DNA. However, MTX has cytotoxicity and neurotoxin may cause multiple organ
injury and is potentially lethal. Thus, the lower toxicity drugs are necessary to
be developed. Recently, diseases treatments with Traditional Chinese Medicine
(TCM) as complements are getting more and more attention. In this study, we
attempted to discover the compounds with drug-like potential for ALL treatment
from the components in TCM. We applied virtual screen and QSAR models based on
structure-based and ligand-based studies to identify the potential TCM component
compounds. Our results show that the TCM compounds adenosine triphosphate,
manninotriose, raffinose, and stachyose could have potential to improve the side
effects of MTX for ALL treatment.
PMID- 25136373
TI - St. John's Wort Has Metabolically Favorable Effects on Adipocytes In Vivo.
AB - In addition to serving as a storage site for reserve energy, adipocytes play a
critical role in whole-body insulin sensitivity and glucose metabolism. St.
John's Wort (SJW) is a botanical supplement widely used as an over-the-counter
treatment of depression and a variety of other conditions associated with anxiety
and nerve pain. Previous studies in our laboratory demonstrated that SJW inhibits
insulin-stimulated glucose uptake and adipocyte differentiation in cultured
murine and mature human adipocytes. To investigate the effects of SJW on
adipocyte function in vivo, we utilized C57BL/6J mice. In our studies, mice were
administered SJW extract (200 mg/kg) once daily by gavage for two weeks. In
contrast to our in vitro studies, mice treated with SJW extract showed increased
levels of adiponectin in white adipose tissue in a depot specific manner (P <
0.01). SJW also exerted an insulin-sensitizing effect as indicated by a
significant increase in insulin-stimulated Akt serine phosphorylation in
epididymal white adipose tissue (P < 0.01). Food intake, body weight, fasting
blood glucose, and fasting insulin did not differ between the two groups. These
results are important as they indicate that SJW does not promote metabolic
dysfunction in adipose tissue in vivo.
PMID- 25136374
TI - Anti-trichophyton activity of protocatechuates and their synergism with
fluconazole.
AB - Dermatophytosis and superficial mycosis are a major global public health problem
that affects 20-25% of the world's population. The increase in fungal resistance
to the commercially available antifungal agents, in conjunction with the limited
spectrum of action of such drugs, emphasises the need to develop new antifungal
agents. Natural products are attractive prototypes for antifungal agents due to
their broad spectrum of biological activities. This study aimed to verify the
antifungal activity of protocatechuic acid, 3,4-diacetoxybenzoic, and fourteen
alkyl protocatechuates (3,4-dihydroxybenzoates) against Trichophyton rubrum and
Trichophyton mentagrophytes and to further assess their activities when combined
with fluconazole. Susceptibility and synergism assays were conducted as described
in M38-A2 (CLSI), with modifications. Three strains of Trichophyton rubrum and
three strains of Trichophyton mentagrophytes were used in this work. The pentyl,
hexyl, heptyl, octyl, nonyl, and decyl protocatechuates showed great fungicidal
effects, with minimum inhibitory concentration (MIC) values ranging from 0.97 to
7.8 mg/L. Heptyl showed a synergistic activity (FIC index = 0.49), reducing the
MIC of fluconazole by fourfold. All substances tested were safe, especially the
hexyl, heptyl, octyl, and nonyl compounds, all of which showed a high selectivity
index, particularly in combination with fluconazole. These ester associations
with fluconazole may represent a promising source of prototypes in the search for
anti-Trichophyton therapeutic agents.
PMID- 25136375
TI - Acupuncture Point Laterality: Investigation of Acute Effects of Quchi (LI11) in
Patients with Hypertension Using Heart Rate Variability.
AB - Hypertension is one of the major risk factors for cardiovascular disease
worldwide. Over 70% of the patients use antihypertensive drugs, so
nonpharmacological treatments in addition to the medication are important. Our
goal was to investigate acupuncture treatment on the Quchi acupoint using heart
rate (HR) and heart rate variability (HRV) and to find out whether there is a
laterality in acute effects. Sixty hypertensive patients (36 female, 24 male;
mean age +/- SD 55.8 +/- 9.7 years) were randomly assigned to two manual needle
acupuncture groups (group A: left Quchi (LI11) acupoint, group B: right Quchi
acupoint). There was a significant (P < 0.05) decrease in HR immediately after
inserting and stimulating the needle at the left and the right Quchi acupuncture
point. In contrast, total HRV increased immediately after inserting the needle,
but this increase was significant only towards the end of the stimulation phase
and after removing the needle. There were some differences between stimulation of
the left and right Quchi acupoint, but they remained insignificant. This study
provides evidence that there is a beneficial effect on heart rate variability in
patients with hypertension and that there are some effects of laterality of the
acupoint Quchi.
PMID- 25136378
TI - Systems and synthetic biology approaches to cell division.
AB - Cells proliferate by division into similar daughter cells, a process that lies at
the heart of cell biology. Extensive research on cell division has led to the
identification of the many components and control elements of the molecular
machinery underlying cellular division. Here we provide a brief review of
prokaryotic and eukaryotic cell division and emphasize how new approaches such as
systems and synthetic biology can provide valuable new insight.
PMID- 25136376
TI - Mouse models of the fragile X premutation and fragile X-associated tremor/ataxia
syndrome.
AB - Carriers of the fragile X premutation (FPM) have CGG trinucleotide repeat
expansions of between 55 and 200 in the 5'-UTR of FMR1, compared to a CGG repeat
length of between 5 and 54 for the general population. Carriers were once thought
to be without symptoms, but it is now recognized that they can develop a variety
of early neurological symptoms as well as being at risk for developing the late
onset neurodegenerative disorder fragile X-associated tremor/ataxia syndrome
(FXTAS). Several mouse models have contributed to our understanding of FPM and
FXTAS, and findings from studies using these models are summarized here. This
review also discusses how this information is improving our understanding of the
molecular and cellular abnormalities that contribute to neurobehavioral features
seen in some FPM carriers and in patients with FXTAS. Mouse models show much of
the pathology seen in FPM carriers and in individuals with FXTAS, including the
presence of elevated levels of Fmr1 mRNA, decreased levels of fragile X mental
retardation protein, and ubiquitin-positive intranuclear inclusions.
Abnormalities in dendritic spine morphology in several brain regions are
associated with neurocognitive deficits in spatial and temporal memory processes,
impaired motor performance, and altered anxiety. In vitro studies have identified
altered dendritic and synaptic architecture associated with abnormal Ca(2+)
dynamics and electrical network activity. FPM mice have been particularly useful
in understanding the roles of Fmr1 mRNA, fragile X mental retardation protein,
and translation of a potentially toxic polyglycine peptide in pathology. Finally,
the potential for using these and emerging mouse models for preclinical
development of therapies to improve neurological function in FXTAS is considered.
PMID- 25136377
TI - The cognitive neuropsychological phenotype of carriers of the FMR1 premutation.
AB - The fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset
neurodegenerative disorder affecting a subset of carriers of the FMR1 (fragile X
mental retardation 1) premutation. Penetrance and expression appear to be
significantly higher in males than females. Although the most obvious aspect of
the phenotype is the movement disorder that gives FXTAS its name, the disorder is
also accompanied by progressive cognitive impairment. In this review, we address
the cognitive neuropsychological and neurophysiological phenotype for males and
females with FXTAS, and for male and female unaffected carriers. Despite
differences in penetrance and expression, the cognitive features of the disorder
appear similar for both genders, with impairment of executive functioning,
working memory, and information processing the most prominent. Deficits in these
functional systems may be largely responsible for impairment on other measures,
including tests of general intelligence and declarative learning. FXTAS is to a
large extent a white matter disease, and the cognitive phenotypes observed are
consistent with what some have described as white matter dementia, in contrast to
the impaired cortical functioning more characteristic of Alzheimer's disease and
related disorders. Although some degree of impaired executive functioning appears
to be ubiquitous among persons with FXTAS, the data suggest that only a subset of
unaffected carriers of the premutation - both female and male - demonstrate such
deficits, which typically are mild. The best-studied phenotype is that of males
with FXTAS. The manifestations of cognitive impairment among asymptomatic male
carriers, and among women with and without FXTAS, are less well understood, but
have come under increased scrutiny.
PMID- 25136379
TI - Swinging a sword: how microtubules search for their targets.
AB - The cell interior is in constant movement, which is to a large extent determined
by microtubules, thin and long filaments that permeate the cytoplasm. To move
large objects, microtubules need to connect them to the site of their
destination. For example, during cell division, microtubules connect chromosomes
with the spindle poles via kinetochores, protein complexes on the chromosomes. A
general question is how microtubules, while being bound to one structure, find
the target that needs to be connected to this structure. Here we review the
mechanisms of how microtubules search for kinetochores, with emphasis on the
recently discovered microtubule feature to explore space by pivoting around the
spindle pole. In addition to accelerating the search for kinetochores, pivoting
helps the microtubules to search for cortical anchors, as well as to self
organize into parallel arrays and asters to target specific regions of the cell.
Thus, microtubule pivoting constitutes a mechanism by which they locate targets
in different cellular contexts.
PMID- 25136380
TI - Microtubule networks for plant cell division.
AB - During cytokinesis the cytoplasm of a cell is divided to form two daughter cells.
In animal cells, the existing plasma membrane is first constricted and then
abscised to generate two individual plasma membranes. Plant cells on the other
hand divide by forming an interior dividing wall, the so-called cell plate, which
is constructed by localized deposition of membrane and cell wall material.
Construction starts in the centre of the cell at the locus of the mitotic spindle
and continues radially towards the existing plasma membrane. Finally the membrane
of the cell plate and plasma membrane fuse to form two individual plasma
membranes. Two microtubule-based cytoskeletal networks, the phragmoplast and the
pre-prophase band (PPB), jointly control cytokinesis in plants. The bipolar
microtubule array of the phragmoplast regulates cell plate deposition towards a
cortical position that is templated by the ring-shaped microtubule array of the
PPB. In contrast to most animal cells, plants do not use centrosomes as foci of
microtubule growth initiation. Instead, plant microtubule networks are striking
examples of self-organizing systems that emerge from physically constrained
interactions of dispersed microtubules. Here we will discuss how microtubule
based activities including growth, shrinkage, severing, sliding, nucleation and
bundling interrelate to jointly generate the required ordered structures.
Evidence mounts that adapter proteins sense the local geometry of microtubules to
locally modulate the activity of proteins involved in microtubule growth
regulation and severing. Many of the proteins and mechanisms involved have roles
in other microtubule assemblies as well, bestowing broader relevance to insights
gained from plants.
PMID- 25136383
TI - Mechanisms of cell division as regulators of acute immune response.
AB - The acute adaptive immune response is complex, proceeding through phases of
activation of quiescent lymphocytes, rapid expansion by cell division and cell
differentiation, cessation of division and eventual death of greater than 95 % of
the newly generated population. Control of the response is not central but
appears to operate as a distributed process where global patterns reliably emerge
as a result of collective behaviour of a large number of autonomous cells. In
this review, we highlight evidence that competing intracellular timed processes
underlie the distribution of individual fates and control cell proliferation,
cessation and loss. These principles can be captured in a mathematical model to
illustrate consistency with previously published experimentally observed data.
PMID- 25136381
TI - When genome integrity and cell cycle decisions collide: roles of polo kinases in
cellular adaptation to DNA damage.
AB - The drive to proliferate and the need to maintain genome integrity are two of the
most powerful forces acting on biological systems. When these forces enter in
conflict, such as in the case of cells experiencing DNA damage, feedback
mechanisms are activated to ensure that cellular proliferation is stopped and no
further damage is introduced while cells repair their chromosomal lesions. In
this circumstance, the DNA damage response dominates over the biological drive to
proliferate, and may even result in programmed cell death if the damage cannot be
repaired efficiently. Interestingly, the drive to proliferate can under specific
conditions overcome the DNA damage response and lead to a reactivation of the
proliferative program in checkpoint-arrested cells. This phenomenon is known as
adaptation to DNA damage and is observed in all eukaryotic species where the
process has been studied, including normal and cancer cells in humans. Polo-like
kinases (PLKs) are critical regulators of the adaptation response to DNA damage
and they play key roles at the interface of cell cycle and checkpoint-related
decisions in cells. Here, we review recent progress in defining the specific
roles of PLKs in the adaptation process and how this conserved family of
eukaryotic kinases can integrate the fundamental need to preserve genomic
integrity with effective cellular proliferation.
PMID- 25136384
TI - Experiments inside a box lead to out-of-the-box ideas on cellular organization.
AB - Microtubules are biopolymers that assemble from tubulin dimers into hollow tubes
and play an important role in cellular organization. Their fascinating properties
and variety of functions, like for example chromosome segregation, sperm
propagation and polarity establishment, have made them a popular subject of
study. In this perspective I focus on the contribution of minimal in vitro
systems to our understanding of microtubule organization within the physical
confinement of a cell.
PMID- 25136382
TI - Role and regulation of kinesin-8 motors through the cell cycle.
AB - Members of the kinesin-8 motor family play a central role in controlling
microtubule length throughout the eukaryotic cell cycle. Inactivation of kinesin
8 causes defects in cell polarity during interphase and astral and mitotic
spindle length, metaphase chromosome alignment, timing of anaphase onset and
accuracy of chromosome segregation. Although the biophysical mechanism by which
kinesin-8 molecules influence microtubule dynamics has been studied extensively
in a variety of species, a consensus view has yet to emerge. One reason for this
might be that some members of the kinesin-8 family can associate to other
microtubule-associated proteins, cell cycle regulatory proteins and other kinesin
family members. In this review we consider how cell cycle specific modification
and its association to other regulatory proteins may modulate the function of
kinesin-8 to enable it to function as a master regulator of microtubule dynamics.
PMID- 25136385
TI - Getting into shape: How do rod-like bacteria control their geometry?
AB - Rod-like bacteria maintain their cylindrical shapes with remarkable precision
during growth. However, they are also capable to adapt their shapes to external
forces and constraints, for example by growing into narrow or curved
confinements. Despite being one of the simplest morphologies, we are still far
from a full understanding of how shape is robustly regulated, and how bacteria
obtain their near-perfect cylindrical shapes with excellent precision. However,
recent experimental and theoretical findings suggest that cell-wall geometry and
mechanical stress play important roles in regulating cell shape in rod-like
bacteria. We review our current understanding of the cell wall architecture and
the growth dynamics, and discuss possible candidates for regulatory cues of shape
regulation in the absence or presence of external constraints. Finally, we
suggest further future experimental and theoretical directions which may help to
shed light on this fundamental problem.
PMID- 25136386
TI - Toward the assembly of a minimal divisome.
AB - The construction of an irreducible minimal cell having all essential attributes
of a living system is one of the biggest challenges facing synthetic biology. One
ubiquitous task accomplished by any living systems is the division of the cell
envelope. Hence, the assembly of an elementary, albeit sufficient, molecular
machinery that supports compartment division, is a crucial step towards the
realization of self-reproducing artificial cells. Looking backward to the
molecular nature of possible ancestral, supposedly more rudimentary, cell
division systems may help to identify a minimal divisome. In light of a possible
evolutionary pathway of division mechanisms from simple lipid vesicles toward
modern life, we define two approaches for recapitulating division in primitive
cells: the membrane deforming protein route and the lipid biosynthesis route.
Having identified possible proteins and working mechanisms participating in
membrane shape alteration, we then discuss how they could be integrated into the
construction framework of a programmable minimal cell relying on gene expression
inside liposomes. The protein synthesis using recombinant elements (PURE) system,
a reconstituted minimal gene expression system, is conceivably the most versatile
synthesis platform. As a first step towards the de novo synthesis of a divisome,
we showed that the N-BAR domain protein produced from its gene could assemble
onto the outer surface of liposomes and sculpt the membrane into tubular
structures. We finally discuss the remaining challenges for building up a self
reproducing minimal cell, in particular the coupling of the division machinery
with volume expansion and genome replication.
PMID- 25136388
TI - Prevalence of group a Beta-hemolytic streptococcus oropharyngeal colonization in
children and therapeutic regimen based on antistreptolysin levels: data from a
city from southern Brazil.
AB - The aim of this study is to determinate the prevalence of oropharyngeal
colonization by group A beta-hemolytic Streptococcus (GABHS) in pediatric
population of Ponta Grossa, a midsize city of southern Brazil; estimate the
effectiveness of antistreptolysin-O (ASO), compared to culture, in presence of
infection; and design an unpublished investigative algorithm of rheumatic fever's
suspicion, based on needs identified in worldwide consensus. It is an
epidemiologic, observational and transversal study, involving 180 children
younger than 12 years. Secretion of posterior oropharynx was collected for
culture; and peripheral blood for determination of ASO. Student-t and chi-square
tests, with Yates correction, were performed for statistical analysis. The ASO
cutoff was determined by Receiver Operating Characteristic (ROC) curve. The
prevalence encountered was 3.9%, and 25.5% of the children showed reagent ASO.
This serological test demonstrated quantitatively and qualitatively significant
associations to the GABHS presence (p=0.0001 for both associations) throughout
the ROC curve, 200 U Todd was the value that resulted in the best accuracy,
demonstrating 100% of sensibility and 80% of specificity in the GAS infection
documentation. Also, it was found that the value of 1.200 U represents a
specificity of 100%. The results emphasize the need for similar studies in other
populations, to provide better targeting of the diagnosis and treatment of
oropharyngitis by GABHS, which in turn can prevent up to 80% the cases of
rheumatic fever, and consequently, the chronic rheumatic heart disease.
PMID- 25136390
TI - The PFNA(r) Augmented in Revision Surgery of Proximal Femur Fractures.
AB - OBJECTIVES: Modern implants for proximal femur fracture treatment have clearly
improved clinical results. However, complications, including cut-out and loss of
reduction, requiring revision surgery still occur. A major challenge in these
cases is a loss of bone stock due to the existing implant, which is usually
exacerbated by osteoporosis. A potential solution is the augmentation of
implants, for example, of the femoral neck blade using bone cement. MATERIALS AND
METHODS: Ten patients (five loosening of femoral neck implant, two
pseudarthrosis, two implant failures and one acute fracture) were included. The
initial hardware was removed and a PFNA augmented was implanted. The perforated
femoral neck blade was augmented using polymethyl methacrylate cement. Clinical
and radiological follow-up was performed at a mean of 5.4 months (SD +/-4.34).
The main outcome parameters were fracture healing and implant-related
complications. RESULTS: Technical handling was uneventful in all cases. No cement
leakage into the joint occurred in any of the cases. The mean amount of cement
injected was 5.3 ml. The fracture healed during follow-up in all cases except two
patients who died from causes unrelated to the procedure and prior to complete
consolidation. Problem-free elective hardware removal of the PFNA augmented was
performed in two cases. DISCUSSION: The PFNA augmented is a potential implant for
joint-preserving revision surgery in proximal femur fractures. The augmentation
improves implant anchorage in the impaired bone stock. In this preliminary
series, no negative biological side effects of the cement (i.e. osteonecrosis)
were observed.
PMID- 25136389
TI - Treatment of femoral neck fracture with a minimal invasive surgical approach for
hemiarthroplasty - clinical and radiological results in 180 geriatric patients.
AB - PURPOSE: The Direct Anterior Approach (DAA) is well established as a minimal
access approach in elective orthopaedic hip surgery. For the growing number of
elderly patients with femoral neck fractures treated with Bipolar Hip
Hemiarthroplasty (BHH), only a few results do exist. The study shows the clinical
and radiological outcome for 180 patients treated by a modified DAA with BHH.
MATERIALS AND METHODS: The data of 180 geriatric patients with medial femoral
neck fractures were evaluated retrospectively. The general and surgical
complications, mobilisation using the Timed Up and Go test (TUG), the social
environment pre- and postoperative and the radiological results have been
compared with established approaches for geriatric hip surgery. RESULTS: After
joint replacement, 18 (10%) patients were developed pneumonia, of which 3 (1.7%)
died during hospitalisation. In 7 cases (4%), surgical revision had to be carried
out: three times (1.7%) because of a seroma, three times (1.7%) because of
subcutaneous infection, and one time (0.6%) because the BHH was removed, owing to
deep wound infection. One dislocation (0.6%) occurred, as well as one femoral
nerve lesion (0.6%) occured. 88.3% of patients were mobilised on walkers or
crutches; the Timed Up and Go Test showed a significant improvement during
inpatient rehabilitation. 83% were discharged to their usual social environment,
10% were transferred to a short-term care facility and 7% were relocated
permanently to a nursing home. 3/4 of patients had a cemented stem alignment in
the range between -5 degrees and 5 degrees , while 2/3 of patients had a maximum
difference of 1 cm in leg length. CONCLUSION: Using the modified DAA, a high
patient satisfaction is achieved after implantation of a BHH. The rate of major
complications is just as low as in conventional approaches, and rapid
mobilisation is possible.
PMID- 25136387
TI - Divided we stand: splitting synthetic cells for their proliferation.
AB - With the recent dawn of synthetic biology, the old idea of man-made artificial
life has gained renewed interest. In the context of a bottom-up approach, this
entails the de novo construction of synthetic cells that can autonomously sustain
themselves and proliferate. Reproduction of a synthetic cell involves the
synthesis of its inner content, replication of its information module, and growth
and division of its shell. Theoretical and experimental analysis of natural cells
shows that, whereas the core synthesis machinery of the information module is
highly conserved, a wide range of solutions have been realized in order to
accomplish division. It is therefore to be expected that there are multiple ways
to engineer division of synthetic cells. Here we survey the field and review
potential routes that can be explored to accomplish the division of bottom-up
designed synthetic cells. We cover a range of complexities from simple abiotic
mechanisms involving splitting of lipid-membrane-encapsulated vesicles due to
physical or chemical principles, to potential division mechanisms of synthetic
cells that are based on prokaryotic division machineries.
PMID- 25136391
TI - Private and Non-Private Disc Herniation Patients: Do they Differ?
AB - OBJECTIVES: In the 2006 yearly report from the Swedish National Register for
Lumbar Spine Surgery it was claimed that international studies show obvious
differences between private and non-private patients with regard to results from
back surgery. Therefore our aim was to reveal such possible differences by
comparing the two categories of patients at a private clinic. MATERIAL AND
METHODS: The material comprises 1184 patients operated on for lumbar disc
herniation during the period of 1987 to 2007. Basic pre-operative data were
obtained from the medical records and follow-up was performed by a questionnaire
around 5 years post-operatively. RESULTS: Small but statistically significant
differences between private and non-private patients were seen pre-operatively
regarding the proportions of a/ men and women in the samples, b/ those with
physically demanding jobs, c/ those on sick leave and d/ those with lumbar pain.
Over the years the admitted private patients had a decreasing mean duration of
symptoms which was not seen in the non-private patients. No apparent differences
(n.s.) were seen between the two categories of patients pre-operatively regarding
age, presence and level of leg pain or the proportion who smoked. Post-operative
improvement in leg and lumbar pain was very similar in private and non-private
patients as was satisfaction with the results and the proportion of patients
returning to work. CONCLUSION: Despite small pre-operative differences concerning
some variables and a significant difference in symptom duration between private
and non-private disc herniation patients, the final clinical results were very
similar.
PMID- 25136392
TI - Lack of relationship between occupational workload and microscopic alterations in
lumbar intervertebral disc disease.
AB - OBJECTIVES: The study investigated the impact of occupational workloads on disc
surgery specimens. We report the relationship between workload and histological
features. METHODS: Specimens were collected prospectively from patients suffering
from lumbar disc prolapse (n=90) or spinal osteochondrosis (n=19).
Histomorphology and occupational workload data and histomorphological features
were evaluated. Occupational data were collected in a structured, standardized
patient interview assessing lifting and carrying loads. In this way the exposure
was assessed for each test subject's entire working life up to surgery. RESULTS:
There was no association between cumulative workload and histological patterns.
In a subgroup of patients with a workload period of 12 months prior to surgery a
relevant formation of chondrocyte clusters (p=0.055) was apparent. Chondrocyte
cluster formation was found in 83% (n=74) of the prolapse patients and in 58%
(n=11) of the osteochondrosis patients (p=0.02). Fibrocyte mediated scar
formation was found in 55% of the prolapse patients and in 45% of the spinal
stenosis patients. Chondrocyte clusters and their de novo collagen matrix did not
integrate biomechanically sufficient with collagen fibers of the disc.
Disintegration of clusters from disc matrix and formation of intra-discal
sequesters were observed. CONCLUSION: Matrix degeneration was common but
displayed no relationship to occupational workload or other histological
features. Scar formation was observed in every second specimen. Regenerative
chondrocyte cluster proliferation was a common feature in disc specimens and
tended to be associated in patients with a workload one year before surgery.
PMID- 25136393
TI - Adherence to treatment: practice, education and research in Danish community
pharmacy.
AB - OBJECTIVE: To describe the practice, education and research concerning medication
adherence in Danish community pharmacy. METHODS: The authors supplemented their
expertise in the area of medication adherence through their contacts with other
educators and researchers as well as by conducting searches in the Danish
Pharmacy Practice Evidence Database, which provides annually updated literature
reviews on intervention research in Danish pharmacy practice. RESULTS: PRACTICE:
Medication adherence is the focus of and/or is supported by a large number of
services and initiatives used in pharmacy practice such as governmental funding,
IT-supported medicine administration systems, dose-dispensing systems, theme
years in pharmacies on adherence and concordance, standards for counselling at
the counter, pharmacist counselling, medication reviews and inhaler technique
assessment. Education: In Denmark, pharmacy and pharmaconomist students are
extensively trained in the theory and practice of adherence to therapy. Pharmacy
staff can choose from a variety of continuing education and post-graduate
programmes which address patient adherence. RESEARCH: Nine ongoing and recently
completed studies are described. Early research in Denmark comprised primarily
smaller, qualitative studies centred on user perspectives, whereas later research
has shifted the focus towards larger, quantitative, controlled studies and action
oriented studies focusing on patient groups with chronic diseases (such as
diabetes, asthma, coronary vascular diseases). CONCLUSIONS: Our analysis has
documented that Danish pharmaceutical education and research has focused strongly
on adherence to treatment for more than three decades. Adherence initiatives in
Danish community pharmacies have developed substantially in the past 5-10 years,
and, as pharmacies have prioritised their role in health care and patient safety,
this development can be expected to continue in future years.
PMID- 25136394
TI - Measuring consumer preference for models of diabetes care delivered by
pharmacists.
AB - Evaluation of a community pharmacy disease management program for type 2
diabetes, 'SugarCare', was conducted. Compared with the standard care offered by
pharmacists, this enhanced program offered patients closer monitoring of blood
glucose levels, counselling about lifestyle, etc. The SugarCare study was funded
by a grant but if the care is to continue some other method of financing must be
found. OBJECTIVES: This study aimed to measure consumer preference for one of the
two types of care offered in the SugarCare study, the control/standard and the
intervention/enhanced service; the strength of that preference; and participants'
willingness to pay (WTP) for their preferred care. METHODS: SugarCare was a
parallel groups, control versus intervention, repeated measures design conducted
in three areas of NSW, Australia. Patients in the Intervention group (enhanced
care) had one initial visit to the pharmacy with six follow up visits over
approximately 9 months. At these visits blood glucose was downloaded and patient
care issues addressed. At the end of the service, a survey instrument was mailed
to the intervention and control participants who were asked to read it and then
expect a telephone call within 2 weeks of receipt. Responses were requested over
the phone and the survey instrument completed by the researcher. WTP data were
collected using a modified payment card method. RESULTS: Overall, 44/75 (59%; 47%
70% 95%CI) respondents expressed a preference for Scenario B (the enhanced care)
while 31/75 (41%; 31%-52% 95%CI) preferred Scenario A (standard care) however,
the difference was not statistically significant. The median maximum WTP was
AUD10 for the enhanced care and AUD3.50 for the standard care (p<0.03).
CONCLUSIONS: While the WTP values expressed were significantly higher for the
enhanced care they did not match with the cost providing that diabetes care.
Discrete choice analysis has the potential to overcome some of the difficulties
encountered with the contingent valuation technique used here. Further research
is required before WTP values such as these could be used with confidence to
determine funding policy.
PMID- 25136395
TI - Beta-blocker therapy in patients with left ventricular systolic dysfunction and
chronic obstructive lung disease in an ambulatory care setting.
AB - OBJECTIVE: To evaluate beta blocker persistence six months after beta-blocker
initiation or dose titration in heart failure (HF) patients with COPD compared to
those without COPD. Secondary objectives included comparison of beta-blocker dose
achieved, changes in left ventricular ejection fraction (LVEF) and incidence of
hospitalizations or emergency department (ED) visits during follow-up. METHODS:
We conducted a matched, retrospective, cohort study including 86 patients with
COPD plus concomitant HF (LVEF <=40%) and 137 patients with HF alone. All
patients were followed in an outpatient HF clinic. Eligible patients had a
documented LVEF <=40% and were initiated or titrated on a beta-blocker in the HF
clinic. Patients were matched based on LVEF (categorized as <= 20% or 21-40%),
gender, and age (> or <=70 years). The primary outcome was beta blocker
persistence at 6 months. Secondary outcomes were dose achieved, LVEF, and
incidence of hospitalizations or ED visits. RESULTS: There were no differences
between the COPD and non-COPD groups in beta-blocker persistence at six-month
follow-up (94.2% vs. 93.4% respectively, adjusted p=0.842). The proportion of
patients who achieved a daily metoprolol dose equivalent of at least 100 mg was
similar between the groups (adjusted p=0.188). The percent of patients with at
least one ED visit or hospitalization in the six-month post-titration period was
substantial but similar between the groups (53.5% and 48.2% for COPD and non-COPD
patients, respectively, adjusted p=0.169). CONCLUSION: Our results support the
use of beta-blockers in the population of heart failure patients with COPD and
without reactive airway disease.
PMID- 25136396
TI - Evaluation of patient perceptions and outcomes related to anticoagulation point
of-care testing in ambulatory care clinics.
AB - Until recently, Prothrombin Time/International Normalized Ratio (PT/INR)
measurements have typically been used to monitor patients on warfarin through
institutional laboratories via venous puncture. The Point-of-Care Testing (POCT)
device has revolutionized the patient care process by allowing for laboratory
testing outside of the central laboratory. OBJECTIVE: To analyze humanistic and
clinical outcomes in patients currently treated with warfarin and monitored
through a pharmacist-managed anticoagulation clinic using point-of-care testing
(POCT) device versus venipuncture within ambulatory care clinics at our
institution. METHODS: All patients currently treated with warfarin therapy who
were managed by clinical pharmacists for anticoagulation monitoring at the
Medical University of South Carolina (MUSC) Family Medicine Center and University
Diagnostic Center, were enrolled. Patients were asked to complete a satisfaction
survey regarding their anticoagulation monitoring. In addition, data related to
emergency department (ED) visits, hospitalizations and percent of time in the INR
therapeutic range for 6 months pre- and post-implementation of POCT device was
collected. This information was obtained through an electronic patient
information database, Oacis. RESULTS: A total of 145 patients were included in
the data collection from the two clinics. The majority (41%) of these patients
were taking warfarin for atrial fibrillation. Satisfaction surveys were completed
by 86 (59 %) of patients. The surveys revealed that POCT device was preferred
over venipuncture in 95% of patients. Reasons for the preference included more
face-to-face interaction, less wait time, less pain, less blood needed, and
quicker results. Of the 145 patients who were included in the objective data
analysis, no significant differences were found in the number of
hospitalizations, ED visits, or percent of time in the INR therapeutic range pre-
and post-implementation of POCT device. CONCLUSION: The results of this study
demonstrate improvement in patient satisfaction with POCT compared to
venipuncture, with limited value in clinical outcomes.
PMID- 25136397
TI - Risk factors of self-reported adverse drug events among Medicare enrollees before
and after Medicare Part D.
AB - OBJECTIVES: Quantify risk factors for self-reported adverse drug events (ADEs)
after the implementation of Medicare Part D, quantify self-reported ADEs before
and after Medicare Part D and quantify the association between self-reported ADEs
and increased use of prescription medication. METHODS: The design was a
longitudinal study including an internet survey before Medicare Part D in 2005
(n=1220) and a follow-up survey in 2007 (n=1024), with n=436 responding to both
surveys. Harris Interactive(r) invited individuals in their online panel to
participate in this study. Individuals who were 65 or older, English speakers, US
residents and enrolled in Medicare were included. Data collected and used in
analysis included self-reported ADE, socio-demographics, self-rated health,
number of medications, symptoms experienced, concern and necessity beliefs about
medicines, number of pharmacies, and whether doses were skipped or stopped to
save money. RESULTS: In 2007, reporting an ADE was related to concern beliefs,
symptoms experienced and age. ADEs were experienced by 18% of respondents in 2005
and 20.4% in 2007. The average number of medications increased from 3.82
(SD=2.82) in 2005 to 4.32 (SD=3.20) in 2007 (t= -5.77, p<0.001). Among
respondents who answered both surveys (n=436), 18.4% reported an ADE in 2005
while 24.3% reported an ADE in 2007. The increase in self-reported ADE was
related to concern beliefs (OR=1.12, 95%CI=1.05, 1.19) and symptoms experienced
(OR= 3.27, 95%CI=1.60, 6.69), not number of medications (OR=1.04, 95%CI=0.77,
1.41). CONCLUSION: Discussing elderly patients' beliefs about their medicines may
affect their medication expectations, symptom interpretation and attributions and
future medication attributions.
PMID- 25136398
TI - Corporate social responsibility in countries with mature and emerging
pharmaceutical sectors.
AB - In recent decades the concept of Corporate Social Responsibility (CSR) has been
adopted by many business sectors, including the pharmaceutical industry. However,
in this and other sectors its application remains variable, particularly between
mature and developing economies. Its stakeholders include pharmacy and medical
students, their attitude to the involvement of companies in socially responsible
activities will be important determinants of public response to the industry.
OBJECTIVE: To investigate the knowledge, attitudes and practices of senior
medical and pharmacy students towards the CSR concept in the pharmaceutical
sector in mature (Germany) and developing (Russia) markets. METHODS: A
questionnaire survey was carried out among senior pharmacy and medical students
during the summer semester 2008 in two Russian and one German university. In each
country 120 questionnaires were distributed. The response rate was 95% in Russia
and 93% in Germany. RESULTS: Although the relevance of CSR was widely
acknowledged by the students, very few were aware of CSR practices currently
performed by companies. THE REPUTATION OF THE PHARMACEUTICAL INDUSTRY WAS
GENERALLY POOR: less than 15% of respondents gave credence to the information
provided in advertisements and fully supported pricing strategies as well as
policies towards the developing countries. When choosing an employer more than
90% of respondents consider the policies affecting an employee directly as
pivotal. However, for a high proportion of students (59% in Russia and 64% in
Germany) socially irresponsible behavior by companies has a significant negative
impact. CONCLUSIONS: This paper identifies practices which students believe
should be a part of the CSR programmes for the pharmaceutical industry, and also
some that should be abandoned. It recommends that corporate communication on CSR
should be expanded. Key differences are seen in perceptions of students in
Germany and Russia towards the extent of irresponsible actions and the variation
between them.
PMID- 25136399
TI - Knowledge and reported use of antibiotics amongst school-teachers in New Zealand.
AB - Gaps in public knowledge about antibiotics have led to calls for public education
campaigns about antibiotics, including education of school children. OBJECTIVE:
This study investigates New Zealand primary school teachers' current level of
knowledge about antibiotics, to assess whether this is adequate for providing
accurate education for children. METHODS: Two hundred and sixty-six primary
school teachers from 39 schools in four cities were interviewed about their
knowledge and understandings of antibiotics, using a questionnaire. RESULTS:
Teachers reported having little current involvement with antibiotics. There were
gaps in the understanding of antibiotics amongst many of the teachers. Only about
60% knew that antibiotics were useful only in bacterial infections, many believed
antibiotics were useful for colds and flu, and many did not know about antibiotic
resistance. On the other hand, teachers largely reported appropriate patterns of
antibiotic use. CONCLUSION: If teachers are to educate children about
antibiotics, basic education about antibiotics and resistance will be required
for school teachers.
PMID- 25136400
TI - Impact of educational intervention on the pattern and incidence of potential drug
drug interactions in Nepal.
AB - OBJECTIVE: To study the impact of educational intervention on the pattern and
incidence of potential drug-drug interactions (DDIs). METHOD: All patients
admitted to Internal Medicine wards of Manipal Teaching Hospital during the study
period were included. Patient details were collected using a patient profile form
and the datum from the filled forms was analyzed using Micromedex electronic
database. An intervention was carried out through a presentation during clinical
meeting and personal discussion. The target groups for the intervention included
doctors and the nurses. RESULTS: Altogether 435 patients during preintervention
and 445 during postintervention were studied. The incidence of potential DDIs was
53% (preintervention) and 41% (postintervention) [chi-square =11.27, p=0.001].
The average number of drugs per patient was 8.53 (pre-intervention) and 7.32
(post-intervention) [t=3.493, p=0.001]. Sixty-four percent of the potential DDIs
were of 'Moderate' type and 58% had a 'Delayed' onset in both the phases. Seventy
percent of the potential DDIs during the pre-intervention phase and 61% during
post-intervention phase had a 'Good' documentation status. Pharmacokinetic
mechanism accounted for 45% of the potential DDIs during preintervention and 36%
in the post-intervention phase. Cardiovascular drugs accounted for 36% of the
potential DDIs during pre-intervention and 33.2% during post-intervention phase.
Furosemide was the high risk drug responsible for DDIs in both phases. The most
common potential DDIs observed were between amlodipine and atenolol (4.82%)
(preintervention) and frusemide and aspirin (5.20%) (postintervention).
CONCLUSION: There was an association between potential DDIs and age, sex, and
polypharmacy.
PMID- 25136401
TI - Collaboration with pharmacy services in a family practice for the medically
underserved.
AB - OBJECTIVES: Pharmacist-managed collaborative services in a family practice
setting are described, and diabetes and hypertension outcomes are assessed.
METHODS: Pharmacist-managed clinics, pharmacotherapy consultations, and drug
information services are provided for a medically underserved, predominantly
African American population. A pharmacy residency director, an ambulatory care
pharmacy resident and three PharmD candidate student pharmacists work directly
with physicians, nurse practitioners, nurses, and social workers to form an
interdisciplinary health care team. Providers utilize pharmacy services through
consultations and referrals. Collaboration outcomes were evaluated in twenty-two
patients with diabetes and thirty hypertensive patients. Patients were
retrospectively followed throughout their history with pharmacy service.
Hemoglobin A1c (A1C) was tracked before referral to pharmacy services, 3 to 6
months after, and as the most current measure after at least 6 months. Blood
pressure (BP) was observed before pharmacy involvement, 2 to 4 months later, and
then currently for at least 4 months with the service. The mean of the most
current markers was calculated, and the percent of patients at their goal marker
was compared to national averages. RESULTS: Fifty percent of pharmacy service
patients met the American Diabetes Association hemoglobin A1c goal of less than
7% in our evaluation compared to the national mean of 49.8% overall and 44% in
African Americans. Thirty percent of patients were at their BP goal while 33.1%
of patients without diabetes and 33.2% of patients with diabetes nationally are
at goal. CONCLUSION: The medically underserved patients under the care of
pharmacy services achieved a higher percentage at their A1C goal than the
national mean. The percentage of patients who achieved their BP goals was
comparable to the national average. Increasing utilization of pharmacy services
in the family practice setting allows for pharmacists and providers to form a
trusted relationship while providing enhanced care and potentially improved
outcomes for patients.
PMID- 25136402
TI - Lung cell-specific modulation of LPS-induced TLR4 receptor and adaptor
localization.
AB - Lung infection by Gram-negative bacteria is a major cause of morbidity and
mortality in humans. Lipopolysaccharide (LPS), located in the outer membrane of
the Gram-negative bacterial cell wall, is a highly potent stimulus of immune and
structural cells via the TLR4/MD2 complex whose function is sequentially
regulated by defined subsets of adaptor proteins. Regulatory mechanisms of lung
specific defense pathways point at the crucial role of resident alveolar
macrophages, alveolar epithelial cells, the TLR4 receptor pathway, and lung
surfactant in shaping the innate immune response to Gram-negative bacteria and
LPS. During the past decade intracellular spatiotemporal localization of TLR4
emerged as a key feature of TLR4 function. Here, we briefly review lung cell type
and compartment-specific mechanisms of LPS-induced TLR4 regulation with a focus
on primary resident hematopoietic and structural cells as well as modifying
microenvironmental factors involved.
PMID- 25136404
TI - Anandamide protects HT22 cells exposed to hydrogen peroxide by inhibiting CB1
receptor-mediated type 2 NADPH oxidase.
AB - BACKGROUND: Endogenous cannabinoid anandamide (AEA) protects neurons from
oxidative injury in rodent models; however the mechanism of AEA-induced
neuroprotection remains to be determined. Activation of neuronal NADPH oxidase 2
(Nox2) contributes to oxidative damage of the brain, and inhibition of Nox2 can
attenuate cerebral oxidative stress. We aimed to determine whether the neuronal
Nox2 was involved in protection mediated by AEA. METHODS: The mouse hippocampal
neuron cell line HT22 was exposed to hydrogen peroxide (H2O2) to mimic oxidative
injury of neurons. The protective effect of AEA was assessed by measuring cell
metabolic activity, apoptosis, lactate dehydrogenase (LDH) release, cellular
morphology, intracellular reactive oxygen species (ROS), and antioxidant and
oxidant levels and Nox2 expression. RESULTS: HT22 cells exposed to H2O2
demonstrated morphological changes, decreased LDH release, reduced metabolic
activity, increased levels of intracellular ROS and oxidized glutathione (GSSG),
reduced levels of superoxide dismutase (SOD), and reduced glutathione (GSH) and
increased expression of Nox2. AEA prevented these effects, a property abolished
by simultaneous administration of CB1 antagonist AM251 or CB1-siRNA. CONCLUSION:
Nox2 inhibition is involved in AEA-induced cytoprotection against oxidative
stress through CB1 activation in HT22 cells.
PMID- 25136405
TI - Transconjunctival inferior orbitotomy: indications, surgical technique, and
complications.
AB - Surgical access to the inferior orbit can be accomplished through either a
transcutaneous or transconjunctival incision. The preferred approach should
provide adequate surgical exposure with the fewest adverse effects. The purpose
of this article is to review the literature on the transconjunctival incision and
to discuss the indications and complications of the approach. The authors also
discuss their preferred technique and provide a step-by-step instruction. The
transconjunctival approach provides good surgical access with a low incidence of
complications and a better aesthetic outcome than transcutaneous approaches.
PMID- 25136403
TI - A review on hemeoxygenase-2: focus on cellular protection and oxygen response.
AB - Hemeoxygenase (HO) system is responsible for cellular heme degradation to
biliverdin, iron, and carbon monoxide. Two isoforms have been reported to date.
Homologous HO-1 and HO-2 are microsomal proteins with more than 45% residue
identity, share a similar fold and catalyze the same reaction. However, important
differences between isoforms also exist. HO-1 isoform has been extensively
studied mainly by its ability to respond to cellular stresses such as hemin,
nitric oxide donors, oxidative damage, hypoxia, hyperthermia, and heavy metals,
between others. On the contrary, due to its apparently constitutive nature, HO-2
has been less studied. Nevertheless, its abundance in tissues such as testis,
endothelial cells, and particularly in brain, has pointed the relevance of HO-2
function. HO-2 presents particular characteristics that made it a unique protein
in the HO system. Since attractive results on HO-2 have been arisen in later
years, we focused this review in the second isoform. We summarize information on
gene description, protein structure, and catalytic activity of HO-2 and
particular facts such as its cellular impact and activity regulation. Finally, we
call attention on the role of HO-2 in oxygen sensing, discussing proposed
hypothesis on heme binding motifs and redox/thiol switches that participate in
oxygen sensing as well as evidences of HO-2 response to hypoxia.
PMID- 25136407
TI - Reconstruction of irradiated mandible after segmental resection of
osteoradionecrosis-a technique employing a microvascular latissimus dorsi flap
and subsequent particulate iliac bone grafting.
AB - The fibula osteocutaneous flap has revolutionized the options of mandibular
segmental defect bridging in osteoradionecrosis (ORN). In selected cases,
however, the fibula flap is not an option because of atherosclerosis or other
features that compromise the vascularity of the lower leg and foot. The aim of
this study is to present an alternative method of mandibular segmental
reconstruction employing a latissimus dorsi (LD) flap and subsequent particulate
iliac free bone graft reconstruction. In 15 patients with ORN, a mandibular
segmental defect was bridged with a reconstruction plate, and the defect site was
primed with a LD musculocutaneous flap wrapped around the reconstruction plate to
bring in vascularized tissue and optimize healing conditions for a subsequent
particulate iliac free bone graft reconstruction. The management of defect
closure was successful in all 15 patients. Twelve patients had a subsequent bone
grafting from the posterior ileum for repair of defects up to 14 cm length. Three
patients had no bone graft for various reasons. In three patients dental
rehabilitation was achieved with implant supported prosthodontic appliances. Ten
patients met the success criteria of uneventful graft healing with restitution of
osseous continuity, mandibular height, symmetry and function, and avoidance of
reconstruction plate fracture.
PMID- 25136408
TI - Survey of Common Practices among Oculofacial Surgeons in the Asia-Pacific Region:
Management of Orbital Floor Blowout Fractures.
AB - A web-based anonymous survey was performed to assess common practices of
oculofacial surgeons in the management of traumatic orbital floor blowout
fractures. A questionnaire which contained questions on several controversial
topics in the management of orbital floor fractures was sent out via e-mail to
131 oculofacial surgeons in 14 countries in the Asia-Pacific region. A total
response rate of 58.3% was achieved from May to December 2012. The preferred time
for surgical intervention was within 2 weeks for adult patients, porous
polyethylene implant was the most popular choice, and most surgeons preferred the
transconjunctival approach. Postoperatively, diplopia was the most commonly
encountered complication and most oculofacial surgeons reviewed their patients
regularly for up to 12 months. We report the results of the first survey of
oculofacial surgeons within the Asia-Pacific region on the management of orbital
floor blowout fractures. Compared with previous surveys (from year 2000 to 2004),
the duration to surgical intervention was comparable but there was a contrasting
change in preferred surgical approach and choice of orbital implant.
PMID- 25136406
TI - Management of carotid artery trauma.
AB - With increased awareness and liberal screening of trauma patients with identified
risk factors, recent case series demonstrate improved early diagnosis of carotid
artery trauma before they become problematio. There remains a need for unified
screening criteria for both intracranial and extracranial carotid trauma. In the
absence of contraindications, antithrombotic agents should be considered in blunt
carotid artery injuries, as there is a significant risk of progression of vessel
injury with observation alone. Despite CTA being used as a common screening
modality, it appears to lack sufficient sensitivity. DSA remains to be the gold
standard in screening. Endovascular techniques are becoming more widely accepted
as the primary surgical modality in the treatment of blunt extracranial carotid
injuries and penetrating/blunt intracranial carotid lessions. Nonetheless, open
surgical approaches are still needed for the treatment of penetrating
extracranial carotid injuries and in patients with unfavorable lesions for
endovascular intervention.
PMID- 25136409
TI - Managing the frontal sinus in the endoscopic age: has the endoscope changed the
algorithm?
AB - Management of fractures involving the frontal sinus seems to be more complex than
merely obtaining an ideal reduction of the bony injuries. Multiple articles on
the management of these fractures suggest that a great deal of controversy
persists despite many years of surgical experience. The question posed in this
article is whether or not the advent of endoscopic approaches has changed or
should change the approaches/algorithms used in the management of these
challenging fractures. It is the conclusion of these authors that endoscopic
techniques can indeed allow us to change the algorithm for management of frontal
sinus trauma. New algorithms are proposed that should provide guidance to
craniomaxillofacial surgeons treating these injuries in the endoscopic age.
PMID- 25136410
TI - Versatility of adipofascial anterolateral thigh flap for reconstruction of
maxillary defects with infratemporal fossa extension.
AB - Tumors arising from the posterior hard palate or posterolateral maxilla may
extend to involve the infratemporal fossa (ITF). Resection of these tumors
results in infrastructural maxillectomy with ITF defects. In this study, we
describe the use of an adipofascial anterolateral thigh flap (ALT) specifically
for such defects. This case series includes four patients who underwent an
infrastructure maxillectomy with ITF clearance and the resultant defects were
reconstructed using adipofascial anterolateral thigh flaps. The complications as
well as the functional outcomes were assessed. This study included patients with
lesions involving the hard palate, posterolateral part of maxilla with extension
into the ITF. The mean flap dimension was 150 cm(2) (range, 120-180 cm(2)). All
flaps were harvested based on a single perforator. The flap was used to
obliterate the ITF defect and also to achieve oroantral separation. All flaps
mucosalized well within 6 weeks. All patients were on oral diet and had adequate
mouth opening. There were no donor-site complications. Adipofascial ALT is an
excellent choice for infrastructural maxillectomy defects with ITF extension. The
intraoral part got mucosalized well and provided a smooth and taut surface. A
large adipofascial tissue flap helps obliterate the ITF, thus minimizing
complications.
PMID- 25136411
TI - A Biomechanical Comparison of Three 1.5-mm Plate and Screw Configurations and a
Single 2.0-mm Plate for Internal Fixation of a Mandibular Condylar Fracture.
AB - The most stable pattern of internal fixation for mandibular condyle fractures is
an area of ongoing discussion. This study investigates the stability of three
patterns of plate fixation using readily available, commercially pure titanium
implants. Finite element models of a simulated mandibular condyle fracture were
constructed. The completed models were heterogeneous in bone material properties,
contained approximately 1.2 million elements and incorporated simulated jaw
adducting musculature. Models were run assuming linear elasticity and isotropic
material properties for bone. No human subjects were involved in this
investigation. The stability of the simulated condylar fracture reduced with the
different implant configurations, and the von Mises stresses of a 1.5-mm X-shaped
plate, a 1.5-mm rectangular plate, and a 1.5-mm square plate (all Synthes
(Synthes GmbH, Zuchwil, Switzerland) were compared. The 1.5-mm X plate was the
most stable of the three 1.5-mm profile plate configurations examined and had
comparable mechanical performance to a single 2.0-mm straight four-hole plate.
This study does not support the use of rectangular or square plate patterns in
the open reduction and internal fixation of mandibular condyle fractures. It does
provide some support for the use of a 1.5-mm X plate to reduce condylar fractures
in selected clinical cases.
PMID- 25136412
TI - Incidence, etiology, and patterns of maxillofacial fractures in ain-shams
university, cairo, egypt: a 4-year retrospective study.
AB - Although there is a worldwide increase in maxillofacial trauma incidence; the
pattern and etiology of these injuries varies from one country to another
depending on socioeconomic, cultural, and environmental factors. This study aims
to realize the epidemiological characteristics of maxillofacial fractures in our
department. A retrospective cross-sectional study of all facial trauma patients
admitted to our department during 2009 to 2012. Patients' data including gender,
age, etiology of trauma, the pattern and demographic distribution of fractures of
maxillofacial skeleton, and associated injuries were analyzed and compared with
previously published data. The chi-square test was used with a p value of less
than 0.05, which was considered statistically significant. There is a significant
increase in maxillofacial fractures incidence in the past 2 years than former
ones. There is a male predominance with highest incidence in the age group of 20
to 40 years. Road traffic accident is the most common etiological factor followed
by violence. There is increase in mandibular fracture incidence compared with
midface. The significant increased incidence of maxillofacial fracture due to
motor car accidents and assaults in the past 2 years reflects a behavioral change
within the community.
PMID- 25136413
TI - Variations in emergence and course of the inferior palpebral nerve.
AB - Comprehensive understanding of the anatomy of the inferior palpebral (IP) nerve
is crucial to preservation of sensation in the inferior eyelid and conjunctiva.
Iatrogenic injuries may occur during blepharoplasty, repair of orbitozygomatic
fracture and other maxillofacial surgeries involving this region. Although
several studies depict the anatomical variations of the main infraorbital nerve
(ION), little information exclusive to the IP nerve exists. This study provides
information on the additional variations of the ION with reference to the IP
nerve. The study was performed on 84 IP nerves by dissection of 42 formalin-fixed
cadavers from the laboratory of topographic anatomy, Department of Human Anatomy,
University of Nairobi, Kenya. Each of the nerves were exposed at the emergence
and followed to their termination. Variations encountered involved emergence,
course, and even absence. Variant emergence was through an accessory infraorbital
foramen, an infraorbital notch, and as a common trunk with the external nasal
nerve. This nerve shows high anatomical variability that may account for the
difficulties and complications encountered in clinical interventions. It is
believed that this information will improve clinical management of conditions
affecting the region of distribution of the IP nerve.
PMID- 25136414
TI - Orbital fracture leading to severe multifascial space infection including the
parapharyngeal space: a report of a case and review of the literature.
AB - Orbital trauma can result in periorbital and orbital infections. Orbital
infections have been classified by Chandler et al in 1970 to their anatomic
location and boundaries. This case report describes a patient who developed a
severe orbital infection following orbital fractures. The infection progressed to
the parapharyngeal space. The patient required multiple incision and drainage
surgeries and tissue debridements to have clinical resolution. To our knowledge,
there has not been a case described in the literature of an orbital infection
progressing to the parapharyngeal space. A literature review of orbital trauma
leading to infection discusses the pathogenesis of the infections. This case
demonstrates that close clinical follow-up and appropriate medical management of
comorbidities that put a patient at higher risk of developing an infection is of
the utmost importance in the treatment of maxillofacial trauma patients.
PMID- 25136415
TI - Subclavicular pectoralis major myocutaneous flap for optimal reconstruction of
large orbitozygomatic defects: a case report.
AB - Since the introduction of microvascular free flaps, the pectoralis major
myocutaneous flap (PMMF) has been relegated to background for most reconstructive
surgeons. The objective of this article is to show the advantages of
cervicofacial defects reconstruction with PMMF using the subclavicular plane
route in a challenging clinical case. An 83-year-old man presented with cutaneous
temporomalar lesion with orbital spread. Tumor resection was performed, including
12 * 11 cm skin and subcutaneous tissue, overlying zygomatic and malar bone, and
orbital exenteration. Radical parotidectomy and functional neck dissection were
performed. PMMF was chosen as reconstructive option routing the pedicle to the
subclavicular plane. The length of the pedicle was 31 cm. The subclavicular route
for PMMF increases the flap's length and arc of rotation compared with the
conventional supraclavicular one. This procedure decreases the bulk of the PMMF
pedicle which makes it functionally and cosmetically favorable. By using this
modification, we may widen the "safe" reconstructive possibilities.
PMID- 25136416
TI - Interesting case: displacement of fractured maxilla into pharyngeal space.
AB - Atypical fracture patterns of the facial region have been reported infrequently.
An unusual displacement of fractured posterior maxillary segment into the lateral
pharyngeal space is described.
PMID- 25136417
TI - Influence of adhesive systems on microtensile bond strength of resin-based
endodontic sealers to the root dentin.
AB - OBJECTIVE: The aim of this study was to determine the microtensile bond strength
to root dentin of AH PlusTM and EndoREZ(r) with Clearfil Liner Bond 2V and
Optibond SoloTM Plus adhesive systems. STUDY DESIGN: The coronal and middle
thirds of six single rooted bovine teeth was split longitudinally in a mesio
distal direction. The two halves were joined with AH Plus or EndoREZ, with and
without the use of Clearfil Liner Bond 2V and Optibond SoloTM Plus adhesive
systems. Build-ups were vertically sectioned into quadrangular (~1mmx1mm)
compound bars and subjected to tensile tests at a constant crosshead speed (1
mm/min) until debonding. RESULTS: Optibond(r) Solo PlusTM in combination with AH
PlusTM and EndoREZ(r) showed the highest mean microtensile bond strength values,
in both coronal and middle thirds. The lowest results were seen in the groups
where no dentine adhesive was applied, and in those where the self-etching
adhesive Clearfil Liner Bond 2V was used. CONCLUSION: The microtensile bond
strength to root dentin of AH PlusTM and EndoREZ may be increased with the use of
a total-etch adhesive. Key words:Adhesive systems, AH Plus, EndoREZ, microtensile
bond strength, root dentin.
PMID- 25136418
TI - Occurrence of contralateral lymph neck node metastasis in patients with squamous
cell carcinoma of the oral cavity.
AB - INTRODUCTION: Squamous cell carcinoma represents about 90% of malignancies of the
mouth and about 38% of the head and neck tumors. The behavior of the cancer is
very aggressive, presenting early cervical metastasis and, often contralateral
ranging from 0.9 to 36%. OBJECTIVES: This study aims to analyze clinical and
pathological factors that may influence metastasis of squamous cell carcinoma in
cervical lymph nodes and relate this occurrence in the contralateral primary
tumor, with disease prognosis and the interference of this type of metastasis in
the survival rate of patients with this pathology. Material and Metohds: It was
conducted a retrospective study from medical records of patients with Squamous
Cell Carcinomas with homolateral lymph node metastasis and contralateral attended
at the clinic of Head and neck surgery of Hospital Sao Vicente de Paulo in Passo
Fundo - RS - Brazil, from 2000 to 2008. RESULTS: Analyzing the charts of patients
with metastatic and metastatic contralateral side it was observed that patients
with initial stage presented a higher survival with statistical significance
(p=0,035). CONCLUSIONS: The occurrence of metastases in lymph nodes of
contralateral position to the primary lesion was not the main fator that
influenced the survival of the group. Key words:Squamous cell carcinoma, oral
cavity, contralateral, death rate, lymphatic metastasis, prognosis.
PMID- 25136419
TI - Association of chronic periodontitis with white blood cell and platelet count - A
Case Control Study.
AB - OBJECTIVES: The objective of the study was to determine whether plasma levels of
white blood corpuscles (WBCs) and platelets were altered in patients with chronic
periodontitis compared to healthy controls. STUDY DESIGN: A total of 120
subjects, 60 with chronic periodontitis and 60 with healthy periodontium of age
group 30-50 years were selected for the study. Oral hygiene status and pocket
probing depth were measured. During clinical evaluation, venous blood samples
were taken to analyze the WBC and platelet counts. Statistical analysis was
utilized to compare differences across various groups. RESULTS: The WBC count was
higher in patients with chronic periodontitis when compared with controls whereas
the platelet count was lower in the case group. CONCLUSIONS: Elevated WBC count
plays a key role in chronic periodontitis and in turn a risk factor for
cardiovascular diseases. However, there is no significant role of platelets in
periodontal infection even though it has a major role in atherogenesis. Key
words:Periodontitis, white blood cells, platelets, cardiovascular diseases.
PMID- 25136420
TI - Clinical evaluation of subepithelial connective tissue graft and guided tissue
regeneration for treatment of Miller's class 1 gingival recession (comparative,
split mouth, six months study).
AB - OBJECTIVES: The present study aims to clinically compare and evaluate
subepithelial connective tissue graft and the GTR based root coverage in
treatment of Miller's Class I gingival recession. STUDY DESIGN: 30 patients with
at least one pair of Miller's Class I gingival recession were treated either with
Subepithelial connective tissue graft (Group A) or Guided tissue regeneration
(Group B). Clinical parameters monitored included recession RD, width of
keratinized gingiva (KG), probing depth (PD), clinical attachment level (CAL),
attached gingiva (AG), residual probing depth (RPD) and % of Root coverage(%RC).
Measurements were taken at baseline, three months and six months. A standard
surgical procedure was used for both Group A and Group B. Data were recorded and
statistical analysis was done for both intergroup and intragroup. RESULTS: At end
of six months % RC obtained were 84.47% (Group A) and 81.67% (Group B). Both
treatments resulted in statistically significant improvement in clinical
parameters. When compared, no statistically significant difference was found
between both groups except in RPD, where it was significantly greater in Group A.
CONCLUSIONS: GTR technique has advantages over subepithelial connective tissue
graft for shallow Miller's Class I defects and this procedure can be used to
avoid patient discomfort and reduce treatment time. Key words:Collagen membrane,
comparative split mouth study, gingival recession, subepithelial connective
tissue graft, guided tissue regeneration (GTR).
PMID- 25136421
TI - How much incisor decompensation is achieved prior to orthognathic surgery?
AB - OBJECTIVES: To quantify incisor decompensation in preparation for orthognathic
surgery. STUDY DESIGN: Pre-treatment and pre-surgery lateral cephalograms for 86
patients who had combined orthodontic and orthognathic treatment were digitised
using OPAL 2.1 [http://www.opalimage.co.uk]. To assess intra-observer
reproducibility, 25 images were re-digitised one month later. Random and
systematic error were assessed using the Dahlberg formula and a two-sample t
test, respectively. Differences in the proportions of cases where the maxillary
(1100 +/- 60) or mandibular (900 +/- 60) incisors were fully decomensated were
assessed using a Chi-square test (p<0.05). Mann-Whitney U tests were used to
identify if there were any differences in the amount of net decompensation for
maxillary and mandibular incisors between the Class II combined and Class III
groups (p<0.05). RESULTS: Random and systematic error were less than 0.5 degrees
and p<0.05, respectively. A greater proportion of cases had decompensated
mandibular incisors (80%) than maxillary incisors (62%) and this difference was
statistically significant (p=0.029). The amount of maxillary incisor
decompensation in the Class II and Class III groups did not statistically differ
(p=0.45) whereas the mandibular incisors in the Class III group underwent
statistically significantly greater decompensation (p=0.02). CONCLUSIONS:
Mandibular incisors were decompensated for a greater proportion of cases than
maxillary incisors in preparation for orthognathic surgery. There was no
difference in the amount of maxillary incisor decompensation between Class II and
Class III cases. There was a greater net decompensation for mandibular incisors
in Class III cases when compared to Class II cases. Key words:Decompensation,
orthognathic, pre-surgical orthodontics, surgical-orthodontic.
PMID- 25136423
TI - Estimation of serum lipids in patients with Oral Submucous Fibrosis in India.
AB - OBJECTIVES: Oral submucous fibrosis (OSMF) is the most prevalent precancerous
condition in India. Low levels of lipids serves as a marker and prognostic
indicator in the early detection of oral precancerous and cancerous states. In
spite of the high prevalence and its potential to undergo malignant
transformation, this condition has not widely been investigated with respect to
the serum lipid levels. In the present study, an attempt was made to analyze the
complete serum lipid profile, total cholesterol (TC), triglycerides (TG), high
density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol
and very low density lipoprotein (VLDL) cholesterol in OSMF and controls.
MATERIAL AND METHODS: The study was conducted in 45 clinically and
histopathologically diagnosed cases of OSMF and 45 age and sex matched controls.
The complete lipid profile including TC, TG, HDL cholesterol, LDL cholesterol and
VLDL cholesterol was analyzed. RESULTS: The serum lipid levels were significantly
lower in the patients with OSMF than in the controls. When the values were
compared between different disease stages, the maximum reduction of lipids was
evident for stage 3 OSMF. From the present results, it is evident that the level
of serum lipids decreases with progression of the disease. CONCLUSIONS: From
these findings, it appears that the decrease in the lipid levels may be
considered as a useful marker in the early diagnosis of oral premalignant
condition like OSMF. Key words:Oral submucous fibrosis, lipids, premalignant
condition.
PMID- 25136422
TI - Clinical and radiographical evaluation of the healing of large periapical lesions
using triple antibiotic paste, photo activated disinfection and calcium hydroxide
when used as root canal disinfectant.
AB - OBJECTIVES: To evaluate clinically and radio graphically, the healing following
nonsurgical treatment of periapical lesions when Photo Activated
Disinfection(PAD), triple antibiotic paste and calcium hydroxide was used as root
canal disinfectant. MATERIAL AND METHODS: Sixty patients (20 for PAD, 20 for
triple antibiotic paste, 20 for calcium hydroxide) with periapical lesions in the
maxillary and mandibular anterior region were selected from the outpatient
section of the Department of Conservative Dentistry & Endodontics, Govt. Dental
College, Kozhikode to participate in this study. The patients were selected with
a preoperative score of 4 or 5. There were no significant differences for the PAI
Scores between the three groups at the start of the experiment .Intracanal
disinfection was done in the three groups followed by obturation. The patients
recalled at 3,6,12,18 months interval. RESULTS: At 18 months follow up 15 % of
cases failed in calcium hydroxide group,5% in triple antibiotic paste and no
failure cases were seen in PAD group. Success criteria were divided into strict
and loose, while the former had statistically significant p value the latter did
not. Kruskal-Wallis Test showed an increased mean value for PDT and a significant
change in p value. Bonferroni post hoc test was done to compare if there is any
significant change between groups. Only significant change was found between
calcium hydroxide and photoactivated disinfection . CONCLUSION: PAD was more
effective intracanal disinfectant at 6,12 and 18 months. Key words:Calcium,
hydroxide, photo activated disinfection, triple antibiotic paste, root canal
disinfection.
PMID- 25136424
TI - Gingival recession: prevalence and risk indicators among young greek adults.
AB - OBJECTIVES: The aim of the current research was to assess the prevalence of
gingival recession and to investigate possible associations among this condition,
periodontal and epidemiological variables in a sample of young Greek adults in a
general dental practice. MATERIAL AND METHODS: A total of 1,430 young adults was
examined clinically and interviewed regarding several periodontal and
epidemiological variables. Collected data included demographic variables, oral
hygiene habits and smoking status. Clinical examination included the recording of
dental plaque, supragingival calculus presence, gingival status and buccal
gingival recession. Multivariate logistic regression analysis model was performed
to access the possible association between gingival recession and several
periodontal and epidemiological variables as potential risk factors. RESULTS: The
overall prevalence of gingival recession was 63.9%. The statistical analysis
indicated that higher educational level [OR= 2.12, 95% CI= 0.53-8.51], cigarette
smoking [OR= 1.97, 95% CI= 1.48-7.91], frequent tooth brushing [OR= 0.98, 95% CI=
0.56-1.96], presence of oral piercing [OR= 0.92, 95% CI= 0.38-1.58], presence of
gingival inflammation [OR= 4.54, 95% CI= 1.68-7.16], presence of dental plaque
[OR= 1.67, 95% CI= 0.68-2.83] and presence of supragingival calculus [OR=1.34,
95% CI= 0.59-1.88], were the most important associated factors of gingival
recession. CONCLUSIONS: The observations of the current research supported the
results from previous authors that several periodontal factors, educational level
and smoking were significantly associated with the presence of gingival
recession, while presence of oral piercing was a new factor that was found to be
associated with gingival recession. Key words:Gingival recession, prevalence,
risk factors, young adults.
PMID- 25136425
TI - Correlation between mutans streptococci counts of parents and their children
residing in Chandigarh, India.
AB - OBJECTIVES: To determine the prevalence of Mutans Streptococci (MS) in children
and to evaluate the relationship between the salivary levels of MS in children
and their parents. MATERIAL AND METHODS: 100 children aged 3-6 years along with
their parents (100 mothers and fathers each) were included in the study. The
children were segregated depending upon their age and level of caries experience.
The children were examined clinically on an ordinary chair in natural daylight
using the Moller's index criteria. Assays for Mutans Streptococci (MS) were done
for both the children and their parents using the Dentocult SM strip mutans test.
Collected data was assessed using SPSS software. RESULTS: The overall prevalence
of MS in the children was 83%. A statistically significant correlation (p<0.05)
was observed between salivary MS counts of children and their mothers. No
significant correlation was seen with the fathers. CONCLUSIONS: The findings
conclude that if primary caregivers harbour high levels of MS in their saliva, it
is likely that their children will have the same. Key words:Mutans streptococci,
parents, children, dentocult SM kits.
PMID- 25136426
TI - Proposed new grading of oral submucous fibrosis based on cheek flexibility.
AB - OBJECTIVES: Oral submucous fibrosis (OSMF) is a potentially malignant disorder of
oral cavity, pharynx and upper digestive tract, characterized by progressive
inability to open the mouth. Based on clinical and/or histopathological features,
various classifications and grading systems have been put forth till date. The
aim of the present study was to study the variance in cheek flexibility in OSMF
patients, the observance of which led to the introduction of a new grading for
the condition. MATERIAL AND METHODS: The study included 412 patients with OSMF
attending to the Department of Oral Medicine and Radiology during the period from
December 2008 to June 2013. A detailed history and examination of the patients
was performed with special emphasis on measuring cheek flexibility. Statistical
analysis was done using Chi-square test and p<0.05 was considered to be
statistically significant. RESULTS: The most common etiological factor was
tobacco (73.3%). All the patients reported with burning sensation of the mouth
and blanching of the mucosa. Malignancy was reported in only 4.6% patients. 60.4%
patients showed cheek flexibility of 30mm and above, while 29.6% patients showed
cheek flexibility between 20-30mm and 10% patients showed less than 30mm of cheek
flexibility. CONCLUSION: The observations of the present study have led to the
proposal of a new grading of OSMF based on cheek flexibility which could assist
in the categorization of the condition by the clinicians. Key words:Cheek
flexibility, oral submucous fibrosis, grading, areca nut.
PMID- 25136428
TI - Comparative study of the efficacy of herbal antioxdants oxitard and aloe vera in
the treatment of oral submucous fibrosis.
AB - OBJECTIVES: Oral submucous fibrosis (OSMF) is a potentially malignant disorder
predominantly seen in the Indian subcontinent due to areca nut, tobacco and their
products. The aim of the present study was to compare the efficacy of oxitard and
aloe vera in the management of OSMF. MATERIAL AND METHODS: 120 subjects with OSMF
were included in the study. The patients were clinico-pathologically diagnosed
and divided equally in 2 groups, Group A (oxitard group) and Group B (aloe vera
group). Group A was administered 2 oxitard capsules twice daily and Group B was
given 5 mg aloe vera gel to be applied topically thrice daily for 3 months.
Different clinical parameters were evaluated at regular intervals. Data was
analyzed using the Student's paired t test and Chi-square test. P-value <0.001
was considered to be statistically significant. RESULTS: Clinical improvements in
mouth opening and tongue protrusion was significant in the oxitard group
(p=0.0005). Subjective symptoms of pain associated with the lesion (p=0.0003),
difficulty in swallowing (p=0.0000) and speech (p=0.0001) also significantly
improved in the Group A. The improvement in burning sensation was not
statistically significant between the 2 groups (p=0.002). There was a mild to
moderate decrease in the size of the lesion. CONCLUSIONS: Though there is no
definitive treatment for the condition however, overall assessment of symptoms
like mouth opening, tongue protrusion, difficulty in swallowing and speech and
pain associated with the lesion showed that oxitard capsules can bring about
significant clinical improvements than aloe vera gel in the treatment of OSMF.
Key words:Oral submucous fibrosis, oxitard capsules, aloe vera, burning
sensation, mouth opening.
PMID- 25136427
TI - Clinical, radiological and therapeutic features of keratocystic odontogenic
tumours: a study over a decade.
AB - Factors associated with the potential for recurrence of keratocystic odontogenic
tumours (KCOT) still remain to be clearly determined and no consensus exists
concerning the management of KCOT. The purpose of this study was to evaluate
different clinical factors associated with KCOT and its treatment methods. A
retrospective review was performed of 55 cases treated from 2001 to 2010. Of the
55 cases, 27% were associated with an impacted or semi-impacted tooth. The
majority of the lesions (82%) were located in tooth-bearing areas, and the
overall mandibular to maxilla ratio of tumour occurrence was 5:1. The treatment
options included enucleation, marsupialisation, or peripheral ostectomy, with or
without the use of Carnoy's solution. Recurrence was found in 14 cases (25%). No
significant association was seen between recurrence and age, symptomatic cases,
location of the lesion, or unilocular or multilocular appearance. The recurrence
rate was higher in the group with tooth involvement, more marked in cases with
third molar involvement. Statistical analysis showed a significant relation
between recurrence and the type of treatment, with higher rates in cases treated
with enucleation associated with tooth extraction. In our series, those cases
with a closer relation with dental tissues showed a higher risk of recurrence,
suggesting the need for a distinct classification for peripheral variants of
KCOT. Key words:Keratocystic odontogenic tumour, Odontogenic keratocyst,
Odontogenic cysts, Keratocyst, Carnoy's solution.
PMID- 25136429
TI - Comparative study of mandibular linear measurements obtained by cone beam
computed tomography and digital calipers.
AB - OBJECTIVES: Cone beam computed tomography (CBCT) is an innovative dental of
imaging system characterized by rapid volumetric imaging with patient exposure to
a single dose of radiation. The present study was carried out to compare the
linear measurements obtained with CBCT and digital caliper in 20 mandibles from
human cadavers. STUDY DESIGN: A total of 4800 linear measurements were measured
between different mandibular anatomical points with CBCT and digital caliper. The
real measurements were defined as those obtained with the digital caliper.
Posteriorly, the mandibles were scanned to obtain the CBCT images, with software
based measurements of the distances. RESULTS: The measurements obtained with the
digital caliper were greater. The CBCT technique underestimated distances greater
than 100 mm. CONCLUSIONS: CBCT allows to obtain linear mandibular anatomical
measurements equivalent to those obtained with digital caliper. The differences
existing between both methods were clinically acceptable. Key words:Computed
tomography, cone beam CT, accuracy, reliability, digital caliper.
PMID- 25136430
TI - Hand skeletal maturity and its correlation with mandibular dental development.
AB - OBJECTIVES: Assessment of pubertal status and pubertal growth spurt in
orthodontic patients has a considerable impact on the diagnosis, treatment plan
and the outcome of orthodontic treatments. Hand-wrist radiography is routinely
used to evaluate skeletal development. Some studies have shown that there is an
association between bone development and different stages of dental
calcification; therefore, the stages of dental calcification can be used as the
first tool for diagnosis, in case there is an association. This study was
performed with the aim to evaluate the association between the phases of dental
development and the stages of skeletal maturity. STUDY DESIGN: In this study, a
total of 52 patients (26 males and 26 females), referring to Mashhad School of
Dentistry for orthodontic treatment, were evaluated; the subjects were within the
age range of 9-14 years. Hand-wrist radiographic evaluation of skeletal
maturation was performed using Fishman method. Also, the Demirjian method was
used to identify the stages of dental calcification by panoramic radiographs.
Independent t-test and Spearman correlation coefficient were used for data
analyses. RESULTS: The mean age of males and females was 11.05 +/- 1.05 and 10.62
+/- 1.12 years, respectively (p=0.156). The Spearman correlation coefficients
between skeletal maturity indicators (SMIs) and developmental stages of
mandibular left and right canines and second molars were significant in males
only (p<0.05). Also, correlation coefficients were significant between adductor
sesamoid ossification and mandibular right and left canines developmental stages
in males (p<0.05). CONCLUSIONS: Findings of this study showed that the
correlation between dental developmental stages and skeletal maturity only were
significant in males; thus, different skeletal maturity patterns in males and
females might be perceptible. Key words:Skeletal maturation, hand-wrist
radiography, panoramic radiography.
PMID- 25136431
TI - Conflict of interest reporting in dentistry meta-analyses: A systematic review.
AB - OBJECTIVES: The issue of reporting conflicts of interest (COI) in medical
research has come under scrutiny over the past decade. Absolute transparency is
important when dealing with conflicts of interest to provide readers with all
essential information required to make an informative decision of the results.
The key objective of this study was to examine the prevalence of reporting
conflicts of interest in therapeutic dental meta-analyses of Randomized Control
Trials (RCTs), and to investigate possible associations with other categorical
variables. STUDY DESIGN: We conducted an extensive literature search across
multiple databases to search for relevant review articles for this study. We
utilized pre-determined key words, and relied on three reviewers to test and
review the use of a data extraction form that was used for the meta-analyses.
Data regarding study characteristics, direction of results, and the significance
of the results from each meta-analysis were extracted. RESULTS: There were 129
meta-analyses used in this review, and the reporting on conflict of interest was
low with only 50 (38.8%) of the articles possessing a conflict of interest
statement (either confirming of denying COI). Of these 50 articles, there were
only 4 (8%) studies that reported an actual conflict of interest. A statement of
conflicts of interest was found in 29 (35.3%) of the papers that reported
significant findings, whereas 35% of the papers that reported positive results
reported on conflict of interest. Prior to 2009, only 17 (25%) papers reported
conflicts of interest, but since 2009, 54.1% of papers collected had a conflict
of interest statement. CONCLUSIONS: Meta-analyses published in the field of
dentistry do not routinely report author conflicts of interest. Although few
conflicts appear to exist, the field of dentistry should continue to ensure that
best evidence reports provide clear and transparent reporting of potential
conflicts of interest in academic journals. Key words:Dentistry, dentition, meta
analysis, quantitative review.
PMID- 25136432
TI - The role of topical simvastatin on bone regeneration: A systematic review.
AB - OBJECTIVES: The aim of this systematic review was to summarize the results
concerning the use of simvastatin for promoting bone regeneration and to discuss
the level of scientific evidence supporting such findings. MATERIAL AND METHODS:
A Pubmed search using "Simvastatin"[Mesh] AND "Bone Regeneration"[Mesh] as
Boolean operators was constrained to the last 10 years and only included papers
written in English. RESULTS: Of the 41 relevant papers reviewed, most of them
(76.2%) have been published in the last 5 years, and most of them address animal
studies (66.6%) performed on rats or rabbits in extraoral regions. Only 4
randomized controlled trials (RCTs) assessed the role of topical simvastatin in
periodontal patients. CONCLUSIONS: A large part of the evidence concerning the
role of topical simvastatin on bone regeneration comes from animal studies
(mainly rats) focusing on extraoral bone defects. Only the use of subgingival
simvastatin after root scaling has been properly supported by RCT. Key
words:Simvastatin, bone regeneration, topical administration, osteogenesis,
osteoinduction.
PMID- 25136434
TI - Sialolithiasis. Proposal for a new minimally invasive procedure: Piezoelectric
surgery.
AB - Sialolithiasis is the presence of stones in the ducts of the salivary glands.
Most episodes are unique, and 60-80% are located exclusively in the main
excretory duct. The main clinical manifestations are swelling and pain typically
before, during or after meals that decreases if the obstruction is not complete.
The highest prevalence of lithiasis is in the submandibular gland -87%-, whose
secretion is more viscous, followed by the parotid gland -10%- and finally the
sublingual gland -3%-. The most significant consequences are caused by the
prolonged blockage of the duct by a stone, which can produce a persistent ductal
dilatation with a swelling that does not subside, and could lead to the complete
degeneration of the parenchyma, becoming a hot spot where secondary infections
may occur, leading to acute bacterial sialadenitis or glandular abscesses.
Treatment options range from a single probing extraction, extraction with
sialographic control using the sialoendoscope, LASER intraductal lithotripsy,
lithotripsy extracorporeal shock wave (ESWL), to the surgical techniques
combining open duct with endoscopic or glandular removal. We propose, with regard
to a case, the use of a simple piezoelectric device which, tunnelling through the
glandular channel by the ostium, allows stone fragmentation, without damaging the
surrounding soft tissue. Stone removal by this less invasive method reduces the
need for more complex and expensive techniques. The postoperative course without
retraction of the ostium, and the regaining of functionality is favourable. Key
words:Calculus, lithotripsy, minimally invasive therapy, piezoelectric surgery,
salivary glands, soft tissues.
PMID- 25136433
TI - Iatrogenic salivary duct injury in head and neck cancer patients: Report of four
cases and review of the literature.
AB - INTRODUCTION: The lesions of the salivary ducts may be idiopathic, post-
traumatic, or iatrogenic and lead to sialocele formation with persistent painful
facial swelling or cutaneous fistula formation. No consensus on treatment of this
condition exists: the options of treatment include needle aspiration, pressure
dressings, antisialogogue therapy, radiotherapy, botulinum toxin and surgical
approaches as duct repair, diversion, ligation, different drainage systems and
even parotidectomy/submaxilectomy. The management and special features of
iatrogenic salivary duct injury in patients with oral cancer who underwent head
and neck reconstructive surgery has not been described yet. MATERIAL AND METHODS:
We present four cases of iatrogenic lesions of salivary ducts and its management
in patients with oral cancer. CONCLUSIONS: The iatrogenic lesions of salivary
ducts are to be taken into account in patients with oral cancer as the distal
ends of salivary ducts could be involved in the margins of surgical resection.
Different options of treatment of this complication are described. Key
words:Sialocele, oral cancer, salivary duct.
PMID- 25136435
TI - Parotid gland solitary fibrous tumor with mandibular bone destruction and
aggressive behavior.
AB - INTRODUCTION: Solitary fibrous tumor is associated with serosal surfaces.
Location in the salivary glands is extremely unusual. Extrathoracic tumors have
an excellent prognosis associated with their benign clinical behavior. We report
an aggressive and recurrent case of this tumor. We review the clinical
presentation, inmunohistochemical profiles and therapeutic approaches. CASE
REPORT: A 73-years-old woman presented a mass in her right parotid gland. She had
a past history of right superficial parotidectomy due to a neurilemoma. FNAB and
magnetic resonance were non-specific. After a tumor resection, microscopic
findings were spindled tumor cells with reactivity to CD34, bcl-2 and CD99 and
the tumor was diagnosed as Solitary Fibrous Tumor. The patient suffered two
recurrences and the tumor had a histological aggressive behavior and a
destruction of the cortical bone of the mandible adjacent to the mass. A marginal
mandibulectomy with an alveolar inferior nerve lateralization was performed.
CONCLUSIONS: Solitary fibrous tumor is a very rare tumor. Usually, they are
benign, but occasionally they can be aggressive. Complete resection is the most
important prognostic factor and no evidence supports the efficacy of any therapy
different to surgery. Due to the unknown prognosis and to the small number of
cases reported, a long-term follow-up is guaranteed. Key words:Solitary fibrous
tumor, parotid mass, parotid gland, salivary gland, rare tumors.
PMID- 25136436
TI - Zinsser-Cole-Engmann syndrome: A rare case report with literature review.
AB - Zinsser-Cole-Engmann syndrome, more commonly known as Dyskeratosis Congenita, is
a heritable genodermatosis having an estimated incidence of 1 in 1 million
people. It is important for an oral physician to be aware of this condition as
oral leukoplakia occurs in this condition as part of a classic triad along with
reticulate skin pigmentation and nail dystrophy. Besides these, there may be
myriad multisystem involvement as well. These individuals have a high
predilection for developing malignancies as well as other grave life-threatening
conditions. Timely diagnosis and management of these cases may help improve their
morbidity and mortality, for which oral physicians can play a major role in
recognizing the cases. This will only be possible when more of such cases are
reported in dental literature. Here we present a case report of a 30 year old
male patient who reported to our department with all the characteristic features
of the triad and a few additional findings concordant to the disease as well. Key
words:Zinsser-Cole-Engmann syndrome, Dyskeratosis Congenita, leukoplakia,
genodermatosis, skin pigmentation, nail dystrophy, progeria, hematological
disturbances.
PMID- 25136437
TI - The craniofacial necrotizing fasciitis after a minor trauma in an elderly white
woman.
AB - The term necrotizing fasciitis /NF/ was probably first described by Jones in 1871
as "hospital gangrene". NF, with its fast spreading from the local infection to
massive necrosis of the underlying tissues, ie. superficial fascia and
subcutaneous layers, is a potentially fatal disease, unless diagnosed early and
properly treated. NF is more frequent in frail patients with chronic debilitating
illnesses, immune deficiencies or from a poor social background. Sixty percent of
NF cases occur in females. Here we present a case of necrotizing fasciitis of the
head and neck region after a minor trauma (phenol blocks due to severe
neuropathic pain) in an 82-year-old female with the history of trigeminal
neuralgia. Key words:Necrotizing fasciitis, craniofacial infection, tissue
necrosis.
PMID- 25136438
TI - Lowering of the mouth floor and vestibuloplasty to support a mandibular
overdenture retained by two implants. A case report.
AB - In Oral Implantology most of the procedures are predictable and have high success
rates. The use of osseointegrated implants as a therapeutic option for the
rehabilitation of patients with severe mandibular atrophy has decreased the need
for pre-prosthetic surgery Nevertheless, complications may occur during implant
surgery and also once the prosthesis has been placed. This paper describes the
case of a totally edentulous patient with an upper complete removable denture and
an implant-retained overdenture with two implants in the intermentonian region.
During clinical examination, the implant abutments were totally covered by soft
tissue since the floor of the mouth was elevated. The panoramic radiography
showed severe mandibular atrophy. Vestibuloplasty was performed together with the
lowering of the floor of the mouth under general anesthesia and nasotracheal
intubation to expose the implants. A new prosthesis was fabricated for the
patient to prevent recurrence and improve the patient's chewing ability as it
formed a physical barrier against soft tissue migration on prosthetic
attachments. Key words:Vestibuloplasty, lowering of the mouth floor,
complications in oral implantology.
PMID- 25136439
TI - Parry Romberg syndrome with localized scleroderma: A case report.
AB - Parry Romberg syndrome(PRS) is a rare acquired poorly understood neurocutaneous
syndrome of unknown etiology characterized by slow progressive atrophic changes
commonly affecting one half of the face. The exact incidence and etiology towards
the syndrome remains unclear. Apart from the multifactorial etiology proposed,
the possible primary cause is mainly attributed to the cerebral disturbance of
the fat metabolism. The syndrome overlaps with "en coup de sabre" morphea, with
an ill defined relationship existing between the two. Parry Romberg Syndrome is
an invalidating lesion that may be associated with different neurological,
cutaneous, ocular, dental and autoimmune abnormalities. This report presents one
rare case of 22 years old female patient with Parry Romberg syndrome associated
with localized scleroderma, accompanied by a brief review of literature with
classical clinical, radiographic, histological findings and the treatment of
progressive hemifacial atrophy. Key words:Parry Romberg syndrome, progressive
facial hemiatrophy, morphea, localized scleroderma.
PMID- 25136440
TI - Traumatic neuroma of the mandible: A case report with spontaneous remission.
AB - Traumatic neuroma is a well-known disorder involving peripheral nerves, which
occurs following trauma or surgery. The lesion develops most commonly in the soft
tissues of the mental foramen area, lower lip and tongue. Intra-osseous lesions
arising in jawbones are very uncommon. In this paper, we report a new case of an
intra-osseous traumatic neuroma, discovered incidentally on a panoramic
radiograph obtained for orthodontic documentation. In addition, the case herein
described developed spontaneous remission, a situation not previously reported in
the literature. Finally, we discuss relevant demographic, clinical, microscopic,
immunohistochemical and treatment aspects of traumatic neuromas. Key
words:Amputation neuroma, traumatic neuroma, mandible, spontaneous remission.
PMID- 25136442
TI - Editorial.
PMID- 25136441
TI - Operational definitions of asthma in recent epidemiological studies are
inconsistent.
AB - OBJECTIVE: The best combination of questions to define asthma in epidemiological
asthma studies is not known. We summarized the operational definitions of asthma
used in prevalence studies and empirically assess how asthma prevalence estimates
vary depending on the definition used. METHODS: We searched the Thomson Reuters
ISI Web of knowledge and included (1) cross-sectional studies (2) on asthma
prevalence (3) conducted in the general population and (4) containing an explicit
definition of asthma. The search was limited to the 100 most-cited papers or
published since January 2010. For each paper, we recorded the asthma definition
used and other variables. Then we applied the definitions to the data of the
Portuguese National Asthma survey (INAsma) and of the 2005-2006 National Health
and Nutrition Examination Survey (NHANES) computing asthma prevalence estimates
for the different definitions. RESULTS: Of 1738 papers retrieved, 117 were
included for analysis. Lifetime asthma, diagnosed asthma and current asthma were
defined in 8, 12 and 29 different ways, respectively. By applying definitions of
current asthma on INAsma and NHANES data, the prevalence ranged between 5.3%
24.4% and 1.1%-17.2%, respectively. CONCLUSIONS: There is considerable
heterogeneity in the definitions of asthma used in epidemiological studies
leading to highly variable estimates of asthma prevalence. Studies to inform a
standardized operational definition are needed. Meanwhile, we propose a set of
questions to be reported when defining asthma in epidemiological studies.
PMID- 25136443
TI - MaxBin: an automated binning method to recover individual genomes from
metagenomes using an expectation-maximization algorithm.
AB - BACKGROUND: Recovering individual genomes from metagenomic datasets allows access
to uncultivated microbial populations that may have important roles in natural
and engineered ecosystems. Understanding the roles of these uncultivated
populations has broad application in ecology, evolution, biotechnology and
medicine. Accurate binning of assembled metagenomic sequences is an essential
step in recovering the genomes and understanding microbial functions. RESULTS: We
have developed a binning algorithm, MaxBin, which automates the binning of
assembled metagenomic scaffolds using an expectation-maximization algorithm after
the assembly of metagenomic sequencing reads. Binning of simulated metagenomic
datasets demonstrated that MaxBin had high levels of accuracy in binning
microbial genomes. MaxBin was used to recover genomes from metagenomic data
obtained through the Human Microbiome Project, which demonstrated its ability to
recover genomes from real metagenomic datasets with variable sequencing
coverages. Application of MaxBin to metagenomes obtained from microbial consortia
adapted to grow on cellulose allowed genomic analysis of new, uncultivated,
cellulolytic bacterial populations, including an abundant myxobacterial
population distantly related to Sorangium cellulosum that possessed a much
smaller genome (5 MB versus 13 to 14 MB) but has a more extensive set of genes
for biomass deconstruction. For the cellulolytic consortia, the MaxBin results
were compared to binning using emergent self-organizing maps (ESOMs) and
differential coverage binning, demonstrating that it performed comparably to
these methods but had distinct advantages in automation, resolution of related
genomes and sensitivity. CONCLUSIONS: The automatic binning software that we
developed successfully classifies assembled sequences in metagenomic datasets
into recovered individual genomes. The isolation of dozens of species in
cellulolytic microbial consortia, including a novel species of myxobacteria that
has the smallest genome among all sequenced aerobic myxobacteria, was easily
achieved using the binning software. This work demonstrates that the processes
required for recovering genomes from assembled metagenomic datasets can be
readily automated, an important advance in understanding the metabolic potential
of microbes in natural environments. MaxBin is available at
https://sourceforge.net/projects/maxbin/.
PMID- 25136444
TI - Obstructive sleep apnea and pulmonary function in patients with severe obesity
before and after bariatric surgery: a randomized clinical trial.
AB - BACKGROUND: The increasing prevalence of obesity in both developed and developing
countries is one of the most serious public health problems and has led to a
global epidemic. Obesity is one of the greatest risk factors of obstructive sleep
apnea (OSA), which is found in 60 to 70% of obese patients mainly due to the
buildup of fat tissue in the upper portion of the thorax and neck. The aim of the
present randomized clinical trial is to assess daytime sleepiness, sleep
architecture and pulmonary function in patients with severe obesity before and
after bariatric surgery. METHODS: This randomized, controlled trial, was
designed, conducted, and reported in accordance with the standards of The CONSORT
(Consolidated Standards of Reporting Trials) Statement. Patients were divided
into a bariatric surgery group and control group. The clinical evaluation was
performed at the Sleep Laboratory of the Nove de JulhoUniversity (Sao Paulo,
Brazil) and consisted of the collection of clinical data, weight, height, body
mass index (BMI), measurements of neck and abdomen circumferences, spirometry,
maximum ventilatory pressure measurements, standard overnight polysomnography
(PSG) and the administration of the Berlin Questionnaire and Epworth Sleepiness
Scale. RESULTS: Fifty-two patients participated in the present study and
performed PSG. Out of these, 16 underwent bariatric surgery. After surgery, mean
BMI decreased from 48.15 +/- 8.58 to 36.91 +/- 6.67 Kg/m(2). Significant
differences were found between the preoperative and postoperative periods
regarding neck (p < 0.001) and waist circumference (p < 0.001), maximum
inspiratory pressure (p = 0.002 and p = 0.004) and maximum expiratory pressure (p
= 0.001 and p = 0.002) for women and men, respectively, as well as sleep stage N3
(p < 0.001), REM sleep (p = 0.049) and the apnea-hypopnea index (p = 0.008).
CONCLUSIONS: Bariatric surgery effectively reduces neck and waist circumference,
increases maximum ventilatory pressures, enhances sleep architecture and reduces
respiratory sleep disorders, specifically obstructive sleep apnea, in patients
with severe obesity. TRIAL REGISTRATION: THE PROTOCOL FOR THIS STUDY WAS
REGISTERED WITH THE WORLD HEALTH ORGANIZATION (UNIVERSAL TRIAL NUMBER: U1111-1121
8873) and Brazilian Registry of Clinical Trials - ReBEC (RBR-9k9hhv).
PMID- 25136446
TI - IgG4-related thyroiditis: a case report and review of literature.
AB - A 55-year-old male, with a positive medical history for hypothyroidism, treated
with stable doses for years was admitted with subacute thyroiditis and a feeling
of pain and pressure in the neck. Laboratory tests showed decrease in TSH levels,
elevated erythrocyte sedimentation rate, and very high antithyroid antibodies.
Owing to enlarging goiter and exacerbation in the patient's complaints, he was
operated with excision of a fibrotic and enlarged thyroid lobe. Elevated IgG4
plasma levels and high IgG4/IgG plasma cell ratio on immunohistochemistry led to
the diagnosis of IgG4-mediated thyroiditis. We concluded that IgG4-thyroiditis
and IgG4-related disease should be considered in all patients with an aggressive
form of Hashimoto's thyroiditis. LEARNING POINTS: IgG4-related disease is a
systemic disease that includes several syndromes; IgG4-related thyroiditis is one
among them.IgG4-thyroiditis should be considered in all patients with an
aggressive form of Hashimoto's thyroiditis.Patients with suspected IgG4
thyroiditis should have blood tested for IgG4/IgG ratio and appropriate
immunohistochemical staining if possible.
PMID- 25136445
TI - Community based interventions for the prevention and control of tuberculosis.
AB - In 2012, an estimated 8.6 million people developed tuberculosis (TB) and 1.3
million died from the disease. With its recent resurgence with the human
immunodeficiency virus (HIV); TB prevention and management has become further
challenging. We systematically evaluated the effectiveness of community based
interventions (CBI) for the prevention and treatment of TB and a total of 41
studies were identified for inclusion. Findings suggest that CBI for TB
prevention and case detection showed significant increase in TB detection rates
(RR: 3.1, 95% CI: 2.92, 3.28) with non-significant impact on TB incidence. CBI
for treating patients with active TB showed an overall improvement in treatment
success rates (RR: 1.09, 95% CI: 1.07, 1.11) and evidence from a single study
suggests significant reduction in relapse rate (RR: 0.26, 95% CI: 0.18, 0.39).
The results were consistent for various study design and delivery mechanism.
Qualitative synthesis suggests that community based TB treatment delivery through
community health workers (CHW) not only improved access and service utilization
but also contributed to capacity building and improving the routine TB recording
and reporting systems. CBI coupled with the DOTS strategy seem to be an effective
approach, however there is a need to evaluate various community-based integrated
delivery models for relative effectiveness.
PMID- 25136447
TI - Recurrent benign adrenal pheochromocytomas associated with hemihypertrophy.
AB - We report a case of a female with hemihypertrophy, who developed five recurrences
of pheochromocytomas until the age of 35. Timely follow-up of the patient's blood
pressure assisted in early diagnosis and treatment of recurrent tumors. LEARNING
POINTS: Recurrent benign pheochromocytomas should raise suspicion of a genetic
syndrome.A pheochromocytoma at a young age has a high propensity to recur and
strict follow-up is mandatory.
PMID- 25136448
TI - A clinically novel AIP mutation in a patient with a very large, apparently
sporadic somatotrope adenoma.
AB - Heterozygous germline inactivating mutations in the aryl hydrocarbon receptor
interacting protein (AIP) gene lead to pituitary adenomas that most frequently
present in the setting of familial isolated pituitary adenoma syndrome, usually
as somatotropinomas and prolactinomas. More recently, they have been found in a
significant percentage of young patients presenting with pituitary macroadenoma
without any apparent family history. We describe the case of a 19-year-old man
who presented with a gigantic somatotropinoma. His family history was negative.
His peripheral DNA showed a heterozygous AIP mutation (p.I13N), while tumor
tissue only had the mutated allele, showing loss of heterozygosity (LOH) and
suggesting that the mutation caused the disease. LEARNING POINTS: AIP mutations
may be observed in sporadic somatotrope adenomas occurring in young patients.LOH
is a strong indicator that an AIP variant is disease causing.Somatotrope adenomas
in carriers of AIP mutations are generally larger and more difficult to cure.
PMID- 25136449
TI - Catecholamine-secreting carotid body paraganglioma: successful preoperative
control of hypertension and clinical symptoms using high-dose long-acting
octreotide.
AB - A 48-year-old hypertensive and diabetic patient presented with a 10-year history
of progressive right facial pain, tinnitus, hearing loss, sweating, and
palpitations. Investigations revealed a 5.6 cm vascular tumor at the carotid
bifurcation. Her blood pressure (BP) was 170/110, on lisinopril 20 mg od and
amlodipine 10 mg od and 100 U of insulin daily. A catecholamine-secreting carotid
body paraganglioma (CSCBP) was suspected; the diagnosis was confirmed
biochemically by determining plasma norepinephrine (NE) level, 89 000 pmol/l, and
chromogranin A (CgA) level, 279 MUg/l. Meta-iodobenzylguanidine and octreotide
scanning confirmed a single tumor in the neck. A week after giving the patient a
trial of octreotide 100 MUg 8 h, the NE level dropped progressively from 50 000
to 25 000 pmol/l and CgA from 279 to 25 MUg/l. Treatment was therefore continued
with labetalol 200 mg twice daily (bid) and long-acting octreotide-LA initially
using 40 mg/month and later increasing to 80 mg/month. On this dose and with a
reduced labetalol intake of 100 mg bid, BP was maintained at 130/70 and her
symptoms resolved completely. CgA levels returned to normal in the first week and
these were maintained throughout the 3 month treatment period. During tumor
resection, there were minimal BP fluctuations during the 10 h procedure. We
conclude that short-term high-dose octreotide-LA might prove valuable in the
preoperative management of catecholamine-secreting tumors. To the best of our
knowledge, this is the first report on the successful use of octreotide in a
CSCBP. LEARNING POINTS: The value of octreotide scanning in the localization of
extra-adrenal pheochromocytoma.Control of catecholamine secretion using high-dose
octreotide.This is a report of a rare cause of secondary diabetes and
hypertension.
PMID- 25136450
TI - Contribution of antimicrobial stewardship programs to reduction of antimicrobial
therapy costs in community hospital with 429 Beds --before-after comparative two
year trial in Japan.
AB - OBJECTIVES: Do antimicrobial stewardship programs (ASPs) contribute to reduction
of antimicrobial therapy costs in Japanese community hospitals? To answer this
health economic question, a before-after comparative two-year trial in a
community hospital in the country was designed. METHODS: The study was conducted
at National Hospital Organization Tochigi Medical Center, a community hospital
with 429 beds. We compared six-month period before-ASP (January 2010 to June
2010) and 24-month period after ASP (July 2010 to June 2012) in primary and
secondary outcome measures. Three medical doctors, three pharmacists and two
microbiology technologists participate in the ASPs. The team then provided
recommendations based on the supplemental elements to primary physicians who
prescribed injectable antimicrobials. Prospective audit with intervention and
feedback was applied in the core strategy while dose optimization, de-escalation
and recommendations for alternate agents and blood cultures were applied in the
supplemental elements. The primary outcome was measured by the antimicrobial
therapy costs (USD per 1,000 patient-days), while the secondary outcomes included
the amount of antimicrobials used (defined daily doses per 1,000 patient-days),
sensitivity rates (%) of Pseudomonas aeruginosa (P. aeruginosa) to Meropenem
(MEPM), Ciprofloxacin (CPFX) and Amikacin (AMK), length of stay (days) and
detection rates (per 1,000 patient-day) of methicillin-resistant Staphylococcus
aureus (MRSA) and extended spectrum beta-lactamase-producing organisms (ESBLs)
through blood cultures. RESULTS: In the study, recommendations were made for 465
cases out of 1,427 cases subject to the core strategy, and recommendations for
251 cases (54.0%) were accepted. After ASP, the antimicrobial therapy costs
decreased by 25.8% (P = 0.005) from those before ASP. Among the secondary
outcomes, significant changes were observed in the amount of aminoglycosides
used, which decreased by 80.0% (P < 0.001) and the detection rate of MRSA, which
decreased by 48.3% (P < 0.001). CONCLUSIONS: The study suggested the possibility
that ASPs contributed to the reduction of the antimicrobial therapy costs in a
community hospital with 429 beds.
PMID- 25136451
TI - The creation of pollution mapping and measurement of ambient concentration of
sulfur dioxide and nitrogen dioxide with passive sampler.
AB - BACKGROUND: Measurements of nitrogen and sulfur dioxide using passive sampler
over 12 months in Samsun, Turkey, are compared with SO2 and NO2 concentrations
obtained from a co-located chemiluminescence analyzer. The concentrations of
Sulfur and nitrogen dioxide in the ambient air during the period from November
2009 to September 2010 are analyzed. RESULTS: The highest value for annual NO2
and SO2 averages of passive sampler was 29.65 MUg/m(3) and 21.01 MUg/m(3) for
exposures of 2-weeks at an industrial site. The maximum monthly concentration for
SO2 was observed at the 10(th) measurement station with 44.19 MUg/m(3) for
August. The maximum monthly concentration for NO2 was observed on the 3(rd)
measurement station with 42.83 MUg/m(3) for November. A negative correlation
between nitrogen dioxide concentrations and temperature (R(2) = -0.5489) was
estimated. A positive correlation between nitrogen dioxide measurement with
passive sampler and continuous measurement (R(2) = 0.6571) was estimated.
PMID- 25136452
TI - The effects of intravitreal bevacizumab in infectious and noninfectious uveitic
macular edema.
AB - Background/Aims. To assess the effect of intravitreal bevacizumab injection
(IVBI) for the treatment of macular edema due to infectious and noninfectious
uveitides. Design. Retrospective interventional case series. Methods. A chart
review was performed on all the patients who were diagnosed with uveitic macular
edema (UME) and received 1.25 mg of IVBI at two referral centers in Riyadh, Saudi
Arabia. All included patients had their visual acuity and macular thickness
analyzed at baseline and at 1 and 3 months following IVBI and any sign of
reactivation was noted. Results. The mean age of patients was 41 +/- 16 years
with a mean followup of 4 +/- 1 months. Ten patients had idiopathic intermediate
uveitis, 9 patients had Behcet's disease, 10 had idiopathic panuveitis, and
twelve patients had presumed ocular tuberculosis uveitis. Following IVBI, the
mean LogMAR visual acuity improved from 0.8 +/- 0.8 at baseline to 0.4 +/- 0.5 at
1 month and 0.3 +/- 0.5 at 3 months (P < 0.002, at 3 months). The mean macular
thickness was 430 +/- 132 MUm at baseline. Following IVBI macular thickness
improved to 286 +/- 93 MUm at 1 month and to 265 +/- 88 MUm at 3 months of
followup (P < 0.001, at 3 months). Conclusion. Bevacizumab was effective in the
management of UME associated with both infectious and noninfectious uveitides.
Intravitreal bevacizumab induced remission of UME with infectious uveitis and had
no immunosuppressive effect against infectious agents.
PMID- 25136453
TI - Evaluation of the Repeatability and the Reproducibility of AL-Scan Measurements
Obtained by Residents.
AB - Purpose. To assess the repeatability and reproducibility of ocular biometry and
intraocular lens (IOL) power measurements obtained by ophthalmology residents
using an AL-Scan device, a novel optical biometer. Methods. Two ophthalmology
residents were instructed regarding the AL-Scan device. Both performed ocular
biometry and IOL power measurements using AL-Scan, three times on each of 128
eyes, independently of one another. Corneal keratometry readings, horizontal iris
width, central corneal thickness, anterior chamber depth, pupil size, and axial
length values measured by both residents were recorded together with IOL power
values calculated on the basis of four different IOL calculation formulas (SRK/T,
Holladay, and HofferQ). Repeatability and reproducibility of the measurements
obtained were analyzed using the intraclass correlation coefficient (ICC).
Results. Repeatability (ICC, 0.872-0.999 for resident 1 versus 0.905-0.999 for
resident 2) and reproducibility (ICC, 0.916-0.999) were high for all biometric
measurements. Repeatability (ICC, 0.981-0.983 for resident 1 versus 0.995-0.996
for resident 2) and reproducibility were also high for all IOL power measurements
(ICC, 0.996 for all). Conclusions. The AL-Scan device exhibits good repeatability
and reproducibility in all biometric measurements and IOL power calculations,
independent of the operator concerned.
PMID- 25136454
TI - Correlation between Intraocular Pressure Fluctuation with Postural Change and
Postoperative Intraocular Pressure in Relation to the Time Course after
Trabeculectomy.
AB - Background. To investigate the correlation between intraocular pressure (IOP)
fluctuation with postural change and IOP in relation to the time course after
trabeculectomy. Methods. A total of 29 patients who had previously undergone
primary trabeculectomy with mitomycin C were examined. IOP was obtained at 1, 2,
3, 6, and 12 months and then every 6 months postoperatively. Results. The
postural IOP difference before surgery was 3.0 +/- 1.8 mmHg, which was reduced to
0.9 +/- 1.1 mmHg at 1 month, 1.0 +/- 1.0 mmHg at 2 months, 1.3 +/- 2.0 mmHg at 3
months, 1.3 +/- 1.4 mmHg at 6 months, 1.4 +/- 1.5 mmHg at 12 months, and 1.1 +/-
0.7 mmHg at 18 months after trabeculectomy (P < 0.01 each visit). The filtering
surgery failed in 7 out of 29 eyes. Postural IOP changes were less than 3 mmHg in
those patients who did not require needle revision at every visit. However, in
patients who did require needle revision, the increase in the posture-induced IOP
was greater than 3 mmHg prior to the increase in the sitting position IOP.
Conclusions. Assessment of postural IOP changes after trabeculectomy might be
potentially useful for predicting IOP changes after trabeculectomy.
PMID- 25136455
TI - Gender and uveitis.
PMID- 25136456
TI - Spectrum of Histomorphologic Findings in Liver in Patients with SLE: A Review.
AB - Collagen vascular diseases (CVDs) like systemic lupus erythematosus (SLE),
rheumatoid arthritis, Sjogren syndrome (SS), and scleroderma are immunologically
mediated disorders that typically have multisystem involvement. Although
clinically significant liver involvement is rare, liver enzyme abnormalities are
common in these patients. The reported prevalence of hepatic involvement in SLE,
histopathologic findings, and its significance is very variable in the existing
literature. It is important to be familiar with the causes of hepatic involvement
in SLE along with histomorphological features which aid in distinguishing
hepatitis of SLE from other hepatic causes as they would alter the patient
management and disease course. Histopathology of liver in SLE shows a wide
morphological spectrum commonly due to a coexisting pathology. Drug induced
hepatitis, viral etiology, and autoimmune overlap should be excluded before
attributing the changes to SLE itself. Common histopathologic findings in SLE
include fatty liver, portal inflammation, and vascular changes like hemangioma,
congestion, nodular regenerative hyperplasia, arteritis, and abnormal vessels in
portal tracts.
PMID- 25136457
TI - Latency after preterm prelabor rupture of the membranes: increased risk for
periventricular leukomalacia.
AB - OBJECTIVE: To identify the risk factors for cystic periventricular leukomalacia
(cPVL) and their implications for deciding between immediate delivery and
conservative management of preterm prelabor rupture of the membranes (pPROM).
METHODS: The following risk factors were compared between cPVL infants and 6440
controls: chorioamnionitis, sex, gestational age (GA), birth weight, pPROM, and
pPROM-delivery interval. Factor impact on cPVL risk and clinical decision-making
was determined by multivariate logistic regression. RESULTS: Overall cPVL
prevalence (n = 32) was 0.99/1000 births. All cPVL infants but one were born <34
weeks of gestation and were <2500 g; 56% had histological chorioamnionitis versus
1.1% of controls (OR 35.9; 95%-CI 12.6-102.7). Because chorioamnionitis is a
postnatal diagnosis, logistic regression was performed with prenatally available
factors: pPROM-delivery interval >48 hours (OR 9.0; 95%-CI 4.1-20.0), male gender
(OR 3.2; 95%-CI 1.4-7.3). GA was not a risk factor if birth weight was included.
Risk decreased with increasing fetal weight despite a prolonged pPROM-delivery
interval. CONCLUSION: pPROM-delivery interval is the single most important
prenatally available risk factor for the development of cPVL. Immediate delivery
favors babies with chorioamnionitis but disfavors those with non infectious
pPROM. In the absence of clinical chorioamnionitis fetal weight gain may offset
the inflammatory risk of cPVL caused by a prolonged pPROM-delivery interval.
PMID- 25136458
TI - Locally advanced and unresectable cutaneous squamous cell carcinoma: outcomes of
concurrent cetuximab and radiotherapy.
AB - Background. Advanced age and immune dysfunction are risk factors for cutaneous
squamous cell carcinoma (cSCC) and often render patients with locally-advanced
disease medically inoperable or surgically unresectable, but potentially curable
with radiotherapy. Concurrent chemotherapy and radiotherapy may not be well
tolerated in this population, but another systemic therapy may improve disease
control. Objective. Determine the tolerance and efficacy of concurrent cetuximab
and radiotherapy (CRT) for patients with locally advanced and unresectable cSCC.
Methods. Retrospective analysis of 12 patients treated with CRT for locally
advanced and unresectable cSCC. Results. Patients were elderly and 75% had
moderate-to-severe comorbidities, while 42% had immune dysfunction. Grades 3-4
adverse events were noted in 83% of patients; 67% required hospital admission for
adverse events. Complete and partial response was noted in 36% and 27% (response
rate, 64%). Stable and progressive disease was noted in 3 and 1 patients,
respectively (disease control rate, 91%). Median progression-free and overall
survival were 6.4 and 8.0 months, respectively. Limitations. Retrospective small
cohort, single-institution analysis. Conclusion. Patients selected for CRT were
elderly, with comorbidities and immune dysfunction, but treatment responses were
observed. Patients selected for this treatment approach have a poor prognosis
with limited capacity for therapy; more effective treatment is needed.
PMID- 25136459
TI - Serum PCSK9 Levels Distinguish Individuals Who Do Not Respond to High-Dose Statin
Therapy with the Expected Reduction in LDL-C.
AB - The purpose of the present report was to examine whether proprotein convertase
subtilisin/kexin type 9 (PCSK9) levels differ in individuals who do not exhibit
expected reductions in low density lipoprotein cholesterol (LDL-C) with statin
therapy. Eighteen nonresponder subjects treated with 80 mg atorvastatin treatment
for 6 months without substantial reductions in LDL-C (DeltaLDL-C: 2.6 +/- 11.4%)
were compared to age- and gender-matched atorvastatin responders (DeltaLDL-C:
50.7 +/- 8.5%) and placebo-treated subjects (DeltaLDL-C: 9.9 +/- 21.5%). Free
PCSK9 was marginally higher in nonresponders at baseline (P = 0.07) and
significantly higher in atorvastatin responders after 6 months of treatment (P =
0.04). The change in free PCSK9 over 6 months with statin treatment was higher (P
< 0.01) in atorvastatin responders (134.2 +/- 131.5 ng/mL post- versus prestudy)
than in either the nonresponders (39.9 +/- 87.8 ng/mL) or placebo subjects (27.8
+/- 97.6 ng/mL). Drug compliance was not lower in the nonresponders as assessed
by pill counts and poststudy plasma atorvastatin levels. Serum PCSK9 levels, both
at baseline and in response to statin therapy, may differentiate individuals who
do versus those who do not respond to statin treatment.
PMID- 25136460
TI - Physicochemical characteristics of citrus seed oils from kerman, iran.
AB - Recently, there has been a great deal of attention on usage, byproducts, and
wastes of the food industry. There have been many studies on the properties of
citrus seeds and extracted oil from citrus grown in Kerman, Iran. The rate of oil
content of citrus seeds varies between 33.4% and 41.9%. Linoleic acid (33.2% to
36.3%) is the key fatty acid found in citrus seeds oil and oleic (24.8% to 29.3%)
and palmitic acids (23.5% to 29.4%) are the next main fatty acids, respectively.
There are also other acids found at trivial rates such as stearic, palmitoleic,
and linolenic. With variation between 0.54 meg/kg and 0.77 mgq/kg in peroxide
values of citrus seed oils, acidity value of the oil varies between 0.44% and
0.72%. The results of the study showed that citrus seeds under study (orange and
sour lemon grown in Kerman province) and the extracted oil have the potential of
being used as the source of edible oil.
PMID- 25136462
TI - Nephrotic syndrome secondary to proliferative glomerulonephritis with monoclonal
immunoglobulin deposits of lambda light chain.
AB - We describe a rare case of a 46-year-old woman with history of refractory
nephrotic syndrome and hypertension who presented with worsening proteinuria and
kidney function. Work-up for both autoimmune and infectious diseases and
hematologic malignancies including multiple myeloma were negative. Kidney biopsy
demonstrated glomerular sclerotic change with lambda light chain deposits in the
subendothelial space, which is consistent with proliferative glomerulonephritis
with monoclonal immunoglobulin deposit (PGNMID). The patient was treated with
bortezomib and dexamethasone without clinical improvement and eventually became
hemodialysis dependent.
PMID- 25136463
TI - Sigmoid colon migration of an intrauterine device.
AB - Background. Intrauterine devices (IUD) are commonly used birth control methods.
Colonic perforation is an infrequent but serious complication of IUD. Case. A 34
year-old woman with 2-years history of IUD, inserted at early puerperal period,
presented to gynecologist with chronic pelvic pain and dyspareunia. Radiological
assessment revealed that there were two copper-T devices: one in uterine cavity
and another in the colonic lumen. Attempts of retrieval with colonoscopy and
laparoscopy were unsuccessful. Intrauterine device embedded in sigmoid colon wall
was removed with resection of the involved segment and primary anastomosis was
performed. Conclusion. Although there are cases in literature that are
successfully managed with colonoscopy, in chronic cases, formation of granulation
tissue complicates retrieval of an IUD by this intervention.
PMID- 25136461
TI - Management of humeral and glenoid bone loss in recurrent glenohumeral
instability.
AB - Recurrent shoulder instability and resultant glenoid and humeral head bone loss
are not infrequently encountered in the population today, specifically in young,
athletic patients. This review on the management of bone loss in recurrent
glenohumeral instability discusses the relevant shoulder anatomy that provides
stability to the shoulder joint, relevant history and physical examination
findings pertinent to recurrent shoulder instability, and the proper radiological
imaging choices in its workup. Operative treatments that can be used to treat
both glenoid and humeral head bone loss are outlined. These include coracoid
transfer procedures and allograft/autograft reconstruction at the glenoid, as
well as humeral head disimpaction/humeroplasty, remplissage, humeral osseous
allograft reconstruction, rotational osteotomy, partial humeral head
arthroplasty, and hemiarthroplasty on the humeral side. Clinical outcomes studies
reporting general results of these techniques are highlighted.
PMID- 25136464
TI - Vaginal septoplasty in septate uterus with double cervix.
AB - Fusion defects of the Mullerian ducts occur frequently and they have been
described by the American Fertility Society. However, septate uterus with
cervical duplication and longitudinal vaginal septum is not described by this
classification and has suggested a change in the classical theory of fusion of
the Mullerian ducts. This paper describes a rare case report of a patient with
complete septate uterus with double cervix and longitudinal vaginal septum,
submitted to the vaginal septoplasty for dyspareunia, progressing to clinical
improvement. The description of this case is to contribute with all uncommon
cases of Mullerian anomalies reports and clinical treatment protocols, which is
not yet established.
PMID- 25136465
TI - Successful laparoscopic management of ruptured tubal pregnancy with an
ipsilateral ectopic pelvic kidney.
AB - Objective. To report a case of successful laparoscopic management of a left
ruptured tubal pregnancy in the setting of an ipsilateral ectopic pelvic kidney.
Method. Case report was prepared at Wayne State University/Detroit Medical
Center. The patient is a young woman gravida 2 para 0 in her twenties who
presented with severe abdominal pain and vaginal bleeding. She had a plateaued
beta HCG and ultrasonographic findings suggestive of ectopic left tubal pregnancy
along with an ectopic ipsilateral pelvic kidney. The IRB approval is not needed,
as this is a case report. The informed consent could not be obtained, as the
patient was not reachable. Result. Multiple intraperitoneal adhesions, left
ruptured ampullary ectopic pregnancy and left retroperitoneal pelvic mass
consistent with ipsilateral ectopic pelvic kidney. Conclusion. Laparoscopic
management of tubal pregnancy can be safely performed in the setting of an
ipsilateral ectopic pelvic kidney.
PMID- 25136466
TI - Mayer-rokitansky-kuster-hauser syndrome associated with severe inferior vena cava
stenosis.
AB - Precis. The postoperative course of a neovagina creation procedure in a young
woman with Meyer-Rokitansky-Kuster-Hauser syndrome was complicated, despite
prophylaxis, by extensive pelvic deep venous thrombosis secondary to unsuspected
severe inferior vena cava stenosis. Background. Mayer-Rokitansky-Kuster-Hauser
(MRKH) syndrome is characterized by congenital vaginal agenesis and an absent or
rudimentary uterus in genotypical females. Malformations of the inferior vena
cava (IVC) are not commonly associated with MRKH syndrome. We report a case of a
patient with MRKH syndrome with severe IVC stenosis that was diagnosed when the
patient presented with extensive pelvic deep venous thrombosis (DVT) during the
postoperative course of a neovagina creation. Case. A 19-year-old female
underwent a McIndoe procedure. Despite DVT prophylaxis, extensive pelvic DVT of
the femoral vein was diagnosed on postoperative day 7. Therapeutic
anticoagulation was initiated, and pharmacological and mechanical thrombolysis
were performed. During these procedures, a hypoplastic IVC was noted. Conclusion.
MRKH syndrome can be associated with IVC malformations, which constitute an
anatomical risk factor for postoperative DVT.
PMID- 25136467
TI - Maintenance therapy with trastuzumab in her2 positive metastatic parotid ductal
adenocarcinoma.
AB - Salivary ductal carcinomas (SDCs) are extremely rare and aggressive malignancies,
accounting for approximately 6% of all salivary gland malignancies. One distinct
feature is their resemblance to ductal carcinomas of breast. A significant
percentage of SDCs overexpress Her2 and the use of targeted therapy with
trastuzumab can be considered in these patients. We report a rare case of long
term disease control with trastuzumab in Her2 positive metastatic parotid ductal
carcinoma. Our case also highlights that isolated brain metastasis should be
managed aggressively to allow optimal local control when systemic disease is
under remission with trastuzumab. We have also reviewed the published literature
on the use of trastuzumab in SDCs.
PMID- 25136468
TI - Myasthenia gravis-like syndrome presenting as a component of the paraneoplastic
syndrome of lung adenocarcinoma in a nonsmoker.
AB - Adenocarcinoma of the lung is the most common form of lung cancer in nonsmokers.
It is commonly seen in the periphery of the lungs. Myasthenia gravis is generally
associated with mediastinal malignancies and rarely associated with
adenocarcinoma of the lung. We present a case of a 38-year-old male nonsmoker
with rapidly progressive adenocarcinoma of the lung associated with myasthenia
gravis, a patient whom expired within 27 days of hospital admission and
diagnosis.
PMID- 25136469
TI - Intra-articular osteoid osteoma mimicking juvenile arthritis.
AB - In case of intra-articular osteoid osteoma, misdiagnosis as juvenile arthritis
may occur, delaying adequate treatment. We report cases of intra-articular
osteoid osteomas in children that were misdiagnosed and initially inappropriately
treated with intra-articular corticoid injection. Diagnosis of osteoid osteoma
was finally given by CT-scan and appropriate treatment by radiofrequency ablation
or surgical ablation was performed. Clinicians and radiologists should be aware
of the potentially confusing clinical and imaging findings associated with intra
articular osteoid osteoma.
PMID- 25136470
TI - Hyperammonemic Encephalopathy due to Valproic Acid and Topiramate Interaction.
AB - Valproic acid-induced hyperammonemic encephalopathy is a rare yet serious adverse
drug reaction. Medication interactions such a valproic acid and topiramate can
precipitate an event. We present the case of a 52-year-old female that presented
with acute mental status change and hypersomnolence due to hyperammonemia caused
by a valproic acid derivative. The patient improved after withdrawal of the
offending medications and treatment with lactulose. Clinicians should remain
hypervigilant in monitoring for valproic acid-induced hyperammonemic
encephalopathy and risk factors such as polypharmacy.
PMID- 25136471
TI - Subcutaneous emphysema, pneumomediastinum, pneumoretroperitoneum, and
pneumoscrotum: unusual complications of acute perforated diverticulitis.
AB - Pneumomediastinum, and subcutaneous emphysema usually result from spontaneous
alveolar wall rupture and, far less commonly, from disruption of the upper
airways or gastrointestinal tract. Subcutaneous neck emphysema,
pneumomediastinum, and retropneumoperitoneum caused by nontraumatic perforations
of the colon have been infrequently reported. The main symptoms of spontaneous
subcutaneous emphysema are swelling and crepitus over the involved site; further
clinical findings in case of subcutaneous cervical and mediastinal emphysema can
be neck and chest pain and dyspnea. Radiological imaging plays an important role
to achieve the correct diagnosis and extension of the disease. We present a quite
rare case of spontaneous subcutaneous cervical emphysema, pneumomediastinum, and
pneumoretroperitoneum due to perforation of an occult sigmoid diverticulum.
Abdomen ultrasound, chest X-rays, and computer tomography (CT) were performed to
evaluate the free gas extension and to identify potential sources of
extravasating gas. Radiological diagnosis was confirmed by the subsequent
surgical exploration.
PMID- 25136472
TI - Forgotten Kirschner wire causing severe hematuria.
AB - Kirschner wire (K-wire) is commonly used in the treatment of hip fracture and its
migration into pelvis leading to bladder injury is a very rare complication.
Nonremoval of these devices either because of lack of followup or because of
prolonged requirement due to disease process is associated with this
complication. We report a case of a patient who presented with acute onset severe
hematuria with clot retention secondary to perforation of bladder by a migrated K
wire placed earlier, for the treatment of hip fracture. Initial imaging showed
its presence in the soft tissues of the pelvis away from the major vascular
structures. Patient was taken for emergency laparotomy and wire was removed after
cystotomy. Postoperative period was uneventful and patient was discharged in
satisfactory condition. K-wires are commonly used in the management of fracture
bones and their migration has been reported in the literature although such
migration in the intrapelvic region involving bladder is very rare. Early
diagnosis and prompt removal of such foreign bodies are required to avert
potentially fatal involvement of major structures.
PMID- 25136473
TI - Effects of whole body vibration and resistance training on bone mineral density
and anthropometry in obese postmenopausal women.
AB - Objective. The aim of this study was to evaluate the impact of two exercise
programs, whole body vibration and resistance training on bone mineral density
(BMD) and anthropometry in obese postmenopausal women. Material and Methods.
Eighty Egyptian obese postmenopausal women were enrolled in this study; their age
ranged from 50 to 68 years. Their body mass index ranged (30-36 kg/m(2)). The
exercise prescription consisted of whole body vibration (WBV) and resistance
training. Bone mineral density (BMD) and anthropometrical parameters were
measured at the beginning and at the end of the study. Changes from baseline to
eight months in BMD and anthropometric parameters were investigated. Results. BMD
at the greater trochanter, at ward's triangle, and at lumbar spine were
significantly higher after physical training, using both WBV and resistive
training. Moreover, both exercise programs were effective in BMI and waist to the
hip ratio. Simple and multiple regression analyses showed significant
associations between physical activity duration and BMD at all sites. The highest
values of R (2) were found for the models incorporating WBV plus BMI. Conclusion.
The study suggests that both types of exercise modalities had a similar positive
effect on BMD at all sites in obese postmenopausal women. Significant association
was noted between physical activity and anthropometric variables and BMD measures
at all sites.
PMID- 25136474
TI - Executive function and postural instability in people with Parkinson's disease.
AB - The specific aspects of cognition contributing to balance and gait have not been
clarified in people with Parkinson's disease (PD). Twenty PD participants and
twenty age- and gender-matched healthy controls were assessed on cognition and
clinical mobility tests. General cognition was assessed with the Mini Mental
State Exam and Addenbrooke's Cognitive Exam. Executive function was evaluated
using the Trail Making Tests (TMT-A and TMT-B) and a computerized cognitive
battery which included a series of choice reaction time (CRT) tests. Clinical
gait and balance measures included the Tinetti, Timed Up & Go, Berg Balance, and
Functional Reach tests. PD participants performed significantly worse than the
controls on the tests of cognitive and executive function, balance, and gait. PD
participants took longer on Trail Making Tests, CRT-Location, and CRT-Colour
(inhibition response). Furthermore, executive function, particularly longer times
on CRT-Distracter and greater errors on the TMT-B, was associated with worse
balance and gait performance in the PD group. Measures of general cognition were
not associated with balance and gait measures in either group. For PD
participants, attention and executive function were impaired. Components of
executive function, particularly those involving inhibition response and
distracters, were associated with poorer balance and gait performance in PD.
PMID- 25136475
TI - The therapeutic effect of zuogui wan in gestational diabetes mellitus rats.
AB - In this experiment, we established an animal model of gestational diabetes
mellitus rats using streptozotocin. Using the rat model of GDM, the pregnant rats
in 1-19d were divided into three groups: (1) Zuogui Wan gestational diabetes
mellitus group (group I, n = 12), (2) gestational diabetes mellitus rats as the
control group (group II, n = 11), and (3) rats of normal pregnancy group (group
III, n = 11). Compared with gestational diabetes mellitus rats as the control
group, Zuogui Wan can change the indexes of fasting blood glucose, body weight,
total cholesterol, insulin, and metabolism cage index significantly in Zuogui Wan
gestational diabetes mellitus group. We can conclude that Zuogui Wan has the
therapeutic effect on gestational diabetes mellitus.
PMID- 25136476
TI - Night-time decibel hell: mapping noise exposure zones and individual annoyance
ratings in an urban environment in ghana.
AB - Although accumulating evidence over the past thirty years indicates that noise is
an environmental stressor in residential settings, much of the data emanated from
studies in high-intensity, noise impact zones around airports or major roads.
Little is known about religious noise, especially at night, which is increasingly
a growing concern for both the general public and policy-makers in sub-Saharan
Africa. Using geographical information systems (GIS), this study measured and
mapped exposure to religious noise in a rapidly urbanising municipality in Ghana.
Quantitative noise risk assessment was used to evaluate the risk of religious
noise-induced hearing loss to residents in the exposed neighbourhoods. The
results show that all neighbourhoods where churches were situated had at least
one location with significant risk of noise-induced hearing loss. However, there
was no statistically significant relationship between neighbourhoods where
religious noise exposure was the highest and where noise annoyance was the
highest. The magnitude of the noise values for night-time exposure is remarkable
particularly given that excessive night-time noise exposure has the greatest
detrimental effect on public health. There is the need to focus on vulnerable
groups, sensitive hours of the night, and possible confounding with air pollution
in order to wholly address this potential hazard.
PMID- 25136477
TI - Joint iris boundary detection and fit: a real-time method for accurate pupil
tracking.
AB - A range of applications in visual science rely on accurate tracking of the human
pupil's movement and contraction in response to light. While the literature for
independent contour detection and fitting of the iris-pupil boundary is vast, a
joint approach, in which it is assumed that the pupil has a given geometric shape
has been largely overlooked. We present here a global method for simultaneously
finding and fitting of an elliptic or circular contour against a dark interior,
which produces consistently accurate results even under non-ideal recording
conditions, such as reflections near and over the boundary, droopy eye lids, or
the sudden formation of tears. The specific form of the proposed optimization
problem allows us to write down closed analytic formulae for the gradient and the
Hessian of the objective function. Moreover, both the objective function and its
derivatives can be cast into vectorized form, making the proposed algorithm
significantly faster than its closest relative in the literature. We compare
methods in multiple ways, both analytically and numerically, using real iris
images as well as idealizations of the iris for which the ground truth boundary
is precisely known. The method proposed here is illustrated under challenging
recording conditions and it is shown to be robust.
PMID- 25136478
TI - Trapping of a single DNA molecule using nanoplasmonic structures for biosensor
applications.
AB - Conventional optical trapping using a tightly focused beam is not suitable for
trapping particles that are smaller than the diffraction limit because of the
increasing need of the incident laser power that could produce permanent thermal
damages. One of the current solutions to this problem is to intensify the local
field enhancement by using nanoplasmonic structures without increasing the laser
power. Nanoplasmonic tweezers have been used for various small molecules but
there is no known report of trapping a single DNA molecule. In this paper, we
present the trapping of a single DNA molecule using a nanohole created on a gold
substrate. Furthermore, we show that the DNA of different lengths can be
differentiated through the measurement of scattering signals leading to possible
new DNA sensor applications.
PMID- 25136479
TI - Self-referenced spectroscopy using plasmon waveguide resonance biosensor.
AB - A plasmon waveguide resonance (PWR) sensor is designed, fabricated, and tested
for self-referenced biosensing. The PWR sensor is able to support two different
polarizations, TM and TE. The TM polarization has a large sensitivity to
variations in the background refractive index while the TE polarization is more
sensitive to the surface properties. The ability of the PWR sensor to
simultaneously operate in both TM and TE modes is used to decouple the background
index variations (bulk effects) from the changes in adlayer thickness (surface
effects) via multimode spectroscopy. To benchmark the performance of the PWR, a
conventional surface plasmon resonance (SPR) sensor is fabricated and tested
under the same conditions.
PMID- 25136480
TI - Photothermal tomography for the functional and structural evaluation, and early
mineral loss monitoring in bones.
AB - Salient features of a new non-ionizing bone diagnostics technique, truncated
correlation photothermal coherence tomography (TC-PCT), exhibiting optical-grade
contrast and capable of resolving the trabecular network in three dimensions
through the cortical region with and without a soft-tissue overlayer are
presented. The absolute nature and early demineralization-detection capability of
a marker called thermal wave occupation index, estimated using the proposed
modality, have been established. Selective imaging of regions of a specific
mineral density range has been demonstrated in a mouse femur. The method is
maximum-permissible-exposure compatible. In a matrix of bone and soft-tissue a
depth range of ~3.8 mm has been achieved, which can be increased through
instrumental and modulation waveform optimization. Furthermore, photoacoustic
microscopy, a comparable modality with TC-PCT, has been used to resolve the
trabecular structure and for comparison with the photothermal tomography.
PMID- 25136481
TI - Gender-related effects of prefrontal cortex connectivity: a resting-state
functional optical tomography study.
AB - The prefrontal cortex (PFC) is thought to play an important role in "higher"
brain functions such as personality and emotion that may associated with several
gender-related mental disorders. In this study, the gender effects of functional
connectivity, cortical lateralization and significantly differences in the PFC
were investigated by using resting-state functional optical tomography (fOT)
measurement. A total of forty subjects including twenty healthy male and twenty
healthy female adults were recruited for this study. In the results, the
hemoglobin responses are higher in the male group. Additionally, male group
exhibited the stronger connectivity in the PFC regions. In the result of
lateralization, leftward dominant was observed in the male group but bilateral
dominance in the female group. Finally, the 11 channels of the inferior PFC
regions (corresponding to the region of Brodmann area 45) are significant
different with spectrum analysis. Our findings suggest that the resting-state fOT
method can provide high potential to apply to clinical neuroscience for several
gender-related mental disorders diagnosis.
PMID- 25136482
TI - Fast wide-field photothermal and quantitative phase cell imaging with optical
lock-in detection.
AB - We present a fast, wide-field holography system for detecting photothermally
excited gold nanospheres with combined quantitative phase imaging. An
interferometric photothermal optical lock-in approach (POLI) is shown to improve
SNR for detecting nanoparticles (NPs) on multiple substrates, including a
monolayer of NPs on a silanized coverslip, and NPs bound to live cells.
Furthermore, the set up allowed for co-registered quantitative phase imaging
(QPI) to be acquired in an off-axis holographic set-up. An SNR of 103 was
obtained for NP-tagging of epidermal growth factor receptor (EGFR) in live cells
with a 3 second acquisition, while an SNR of 47 was seen for 20 ms acquisition.
An analysis of improvements in SNR due to averaging multiple frames is presented,
which suggest that residual photothermal signal can be a limiting factor. The
combination of techniques allows for high resolution imaging of cell structure
via QPI with the ability to identify receptor expression via POLI.
PMID- 25136483
TI - Nonlinear structured-illumination enhanced temporal focusing multiphoton
excitation microscopy with a digital micromirror device.
AB - In this study, the light diffraction of temporal focusing multiphoton excitation
microscopy (TFMPEM) and the excitation patterning of nonlinear structured
illumination microscopy (NSIM) can be simultaneously and accurately implemented
via a single high-resolution digital micromirror device. The lateral and axial
spatial resolutions of the TFMPEM are remarkably improved through the second
order NSIM and projected structured light, respectively. The experimental results
demonstrate that the lateral and axial resolutions are enhanced from 397 nm to
168 nm (2.4-fold) and from 2.33 MUm to 1.22 MUm (1.9-fold), respectively, in full
width at the half maximum. Furthermore, a three-dimensionally rendered image of a
cytoskeleton cell featuring ~25 nm microtubules is improved, with other
microtubules at a distance near the lateral resolution of 168 nm also able to be
distinguished.
PMID- 25136484
TI - Development of a luminous textile for reflective pulse oximetry measurements.
AB - In this paper, a textile-based sensing principle for long term
photopletysmography (PPG) monitoring is presented. Optical fibers were
embroidered into textiles such that out-coupling and in-coupling of light was
possible. The "light-in light-out" properties of the textile enabled the
spectroscopic characterization of human tissue. For the optimization of the
textile sensor, three different carrier fabrics and different fiber modifications
were compared. The sample with best light coupling efficiency was successfully
used to measure heart rate and SpO2 values of a subject. The latter was
determined by using a modified Beer-Lambert law and measuring the light
attenuation at two different wavelengths (632 nm and 894 nm). Moreover, the
system was adapted to work in reflection mode which makes the sensor more
versatile. The measurements were additionally compared with commercially
available system and showed good correlation.
PMID- 25136485
TI - Characterization and in-vivo evaluation of a multi-resolution foveated
laparoscope for minimally invasive surgery.
AB - The state-of-the-art laparoscope lacks the ability to capture high-magnification
and wide-angle images simultaneously, which introduces challenges when both close
up views for details and wide-angle overviews for orientation are required in
clinical practice. A multi-resolution foveated laparoscope (MRFL) which can
provide the surgeon both high-magnification close-up and wide-angle images was
proposed to address the limitations of the state-of-art surgical laparoscopes. In
this paper, we present the overall system design from both clinical and optical
system perspectives along with a set of experiments to characterize the optical
performances of our prototype system and describe our preliminary in-vivo
evaluation of the prototype with a pig model. The experimental results
demonstrate that at the optimum working distance of 120mm, the high-magnification
probe has a resolution of 6.35lp/mm and image a surgical area of 53 * 40mm(2);
the wide-angle probe provides a surgical area coverage of 160 * 120mm(2) with a
resolution of 2.83lp/mm. The in-vivo evaluation demonstrates that MRFL has great
potential in clinical applications for improving the safety and efficiency of the
laparoscopic surgery.
PMID- 25136486
TI - Improving high resolution retinal image quality using speckle illumination HiLo
imaging.
AB - Retinal image quality from flood illumination adaptive optics (AO)
ophthalmoscopes is adversely affected by out-of-focus light scatter due to the
lack of confocality. This effect is more pronounced in small eyes, such as that
of rodents, because the requisite high optical power confers a large dioptric
thickness to the retina. A recently-developed structured illumination microscopy
(SIM) technique called HiLo imaging has been shown to reduce the effect of out-of
focus light scatter in flood illumination microscopes and produce pseudo-confocal
images with significantly improved image quality. In this work, we adopted the
HiLo technique to a flood AO ophthalmoscope and performed AO imaging in both
(physical) model and live rat eyes. The improvement in image quality from HiLo
imaging is shown both qualitatively and quantitatively by using spatial spectral
analysis.
PMID- 25136487
TI - Optimized approaches for optical sectioning and resolution enhancement in 2D
structured illumination microscopy.
AB - The use of structured illumination in fluorescence microscopy allows the
suppression of out of focus light and an increase in effective spatial
resolution. In this paper we consider different approaches for reconstructing 2D
structured illumination images in order to combine these two attributes, to allow
fast, optically sectioned, superresolution imaging. We present a linear
reconstruction method that maximizes the axial frequency extent of the combined
2D structured illumination passband along with an empirically optimized
approximation to this scheme. These reconstruction methods are compared to other
schemes using structured illumination images of fluorescent samples. For
sinusoidal excitation at half the incoherent cutoff frequency we find that
removing information in the zero order passband except for a small region close
to the excitation frequency, where it replaces the complementary information from
the displaced first order passband, enables optimal reconstruction of optically
sectioned images with enhanced spatial resolution.
PMID- 25136488
TI - Quantitative 3D-OCT motion correction with tilt and illumination correction,
robust similarity measure and regularization.
AB - Variability in illumination, signal quality, tilt and the amount of motion pose
challenges for post-processing based 3D-OCT motion correction algorithms. We
present an advanced 3D-OCT motion correction algorithm using image registration
and orthogonal raster scan patterns aimed at addressing these challenges. An
intensity similarity measure using the pseudo Huber norm and a regularization
scheme based on a pseudo L0.5 norm are introduced. A two-stage registration
approach was developed. In the first stage, only axial motion and axial tilt are
coarsely corrected. This result is then used as the starting point for a second
stage full optimization. In preprocessing, a bias field estimation based approach
to correct illumination differences in the input volumes is employed.
Quantitative evaluation was performed using a large set of data acquired from 73
healthy and glaucomatous eyes using SD-OCT systems. OCT volumes of both the optic
nerve head and the macula region acquired with three independent orthogonal
volume pairs for each location were used to assess reproducibility. The advanced
motion correction algorithm using the techniques presented in this paper was
compared to a basic algorithm corresponding to an earlier version and to
performing no motion correction. Errors in segmentation-based measures such as
layer positions, retinal and nerve fiber thickness, as well as the blood vessel
pattern were evaluated. The quantitative results consistently show that
reproducibility is improved considerably by using the advanced algorithm, which
also significantly outperforms the basic algorithm. The mean of the mean absolute
retinal thickness difference over all data was 9.9 um without motion correction,
7.1 um using the basic algorithm and 5.0 um using the advanced algorithm.
Similarly, the blood vessel likelihood map error is reduced to 69% of the
uncorrected error for the basic and to 47% of the uncorrected error for the
advanced algorithm. These results demonstrate that our advanced motion correction
algorithm has the potential to improve the reliability of quantitative
measurements derived from 3D-OCT data substantially.
PMID- 25136489
TI - Direct observation and validation of fluorescein tear film break-up patterns by
using a dual thermal-fluorescent imaging system.
AB - The fluorescein tear film break-up test is a common tear film stability test for
dry eye diagnosis. This test requires applying fluorescein sodium drops to a tear
film to observe the tear film break-up. However, this test is limited by using
the fluorescein sodium drops, which can induce reflex tearing and reduce the
reliability of the diagnosis results. This paper proposes that tear film
evaporation accelerates on the fluorescein tear film break-up area (FTBA),
resulting in a lower temperature area (LTA) on the tear film. A dual modality
system was established to capture the thermal and fluorescent image of
fluorescein-stain tear films for 48 participants. Observations showed that the
LTA and FTBA were highly correlated in their location (r = 0.82) and size (r =
0.91). This is first study to show that the FTBA and LTA are essentially the same
region. This study demonstrated the feasibility of using the noncontact
thermograph method to evaluate tear film stability without using a fluorescein
sodium drop.
PMID- 25136490
TI - In vivo imaging of functional microvasculature within tissue beds of oral and
nasal cavities by swept-source optical coherence tomography with a forward/side
viewing probe.
AB - We report three-dimensional (3D) imaging of microcirculation within human cavity
tissues in vivo using a high-speed swept-source optical coherence tomography (SS
OCT) at 1300 nm with a modified probe interface. Volumetric structural OCT images
of the inner tissues of oral and nasal cavities are acquired with a field of view
of 2 mm * 2 mm. Two types of disposable and detachable probe attachments are
devised and applied to the port of the imaging probe of OCT system, enabling
forward and side imaging scans for selective and easy access to specific cavity
tissue sites. Blood perfusion is mapped with OCT-based microangiography from 3D
structural OCT images, in which a novel vessel extraction algorithm is used to
decouple dynamic light scattering signals, due to moving blood cells, from the
background scattering signals due to static tissue elements. Characteristic
tissue anatomy and microvessel architectures of various cavity tissue regions of
a healthy human volunteer are identified with the 3D OCT images and the
corresponding 3D vascular perfusion maps at a level approaching capillary
resolution. The initial finding suggests that the proposed method may be
engineered into a promising tool for evaluating and monitoring tissue
microcirculation and its alteration within a wide-range of cavity tissues in the
patients with various pathological conditions.
PMID- 25136491
TI - High resolution three-dimensional photoacoutic tomography with CCD-camera based
ultrasound detection.
AB - A photoacoustic tomograph based on optical ultrasound detection is demonstrated,
which is capable of high resolution real-time projection imaging and fast three
dimensional (3D) imaging. Snapshots of the pressure field outside the imaged
object are taken at defined delay times after photoacoustic excitation by use of
a charge coupled device (CCD) camera in combination with an optical phase
contrast method. From the obtained wave patterns photoacoustic projection images
are reconstructed using a back propagation Fourier domain reconstruction
algorithm. Applying the inverse Radon transform to a set of projections recorded
over a half rotation of the sample provides 3D photoacoustic tomography images in
less than one minute with a resolution below 100 um. The sensitivity of the
device was experimentally determined to be 5.1 kPa over a projection length of 1
mm. In vivo images of the vasculature of a mouse demonstrate the potential of the
developed method for biomedical applications.
PMID- 25136492
TI - Calcium imaging at kHz frame rates resolves millisecond timing in neuronal
circuits and varicosities.
AB - We have configured a widefield fast imaging system that allows imaging at 1000
frames per second (512x512 pixels). The system was extended with custom
processing tools including a time correlation method to facilitate the analysis
of static subcellular compartments (e.g. neuronal varicosities) with enhanced
contrast, as well as a dynamic intensity processing (DIP) algorithm that aids in
data size reduction and fast visualization and interpretation of timing and
directionality in neuronal circuits. This system, together with our custom
developed processing tools enables efficient detection of fast physiological
events, such as action potential dependent calcium steps. We show, using a
specific blocker of nerve communication, that with this setup it is possible to
discriminate between a pre and post synaptic event in an all optical way.
PMID- 25136493
TI - In vivo quantitative photoacoustic microscopy of gold nanostar kinetics in mouse
organs.
AB - We developed a high-resolution photoacoustic microscopy (PAM) system with a near
infrared (NIR) laser to noninvasively monitor the distribution of gold nanostar
(GNS) in blood vessels, liver and spleen in mice. Photoacoustic images of organs
at deep depths were continuously acquired in vivo every 30 minutes after a single
dose of GNS by tail vein injection. The experimental results showed that GNS
accumulated significantly in both liver and spleen from blood circulation after
administration, which was qualitatively validated by fluorescence imaging. Our
studies demonstrate that PAM might be potentially used for noninvasive tracing
the kinetics of exogenous nanoparticles in biological system.
PMID- 25136494
TI - Surface modification of silica particles with gold nanoparticles as an
augmentation of gold nanoparticle mediated laser perforation.
AB - Gold nanoparticle mediated (GNOME) laser transfection/perforation fulfills the
demands of a reliable transfection technique. It provides efficient delivery and
has a negligible impact on cell viability. Furthermore, it reaches high
throughput applicability. However, currently only large gold particles (> 80 nm)
allow successful GNOME laser perforation, probably due to insufficient
sedimentation of smaller gold nanoparticles. The objective of this study is to
determine whether this aspect can be addressed by a modification of silica
particles with gold nanoparticles. Throughout the analysis, we show that after
the attachment of gold nanoparticles to silica particles, comparable or better
efficiencies to GNOME laser perforation are reached. In combination with 1 um
silica particles, we report laser perforation with gold nanoparticles with sizes
down to 4 nm. Therefore, our investigations have great importance for the future
research in and the fields of laser transfection combined with plasmonics.
PMID- 25136495
TI - Optical design and evaluation of a 4 mm cost-effective ultra-high-definition
arthroscope.
AB - High definition and magnification rigid endoscope plays an important role in
modern minimally invasive medical surgery and diagnosis. In this paper, we
present the design and evaluation methods of a high definition rigid endoscope,
specifically an arthroscope, with a large depth of field (DOF). The incident
heights and exit angles of the sampled rays on the relay lens are controlled
during the optimization process to ensure an effective field view (70 degrees )
and a normal ray path within the limited lens diameter of 2.7 mm. The lens is set
up as a multi-configuration system with two extreme and one middle object
distances to cover a large DOF. As a result, an entrance pupil of 0.3 mm is
achieved for the first time, to bring the theoretical resolution to 23.1 lps/mm
in the object space at a working distance of 20 mm, with the wavelength of 0.532
um. The modulation transfer function (MTF) curves approach diffraction limit, and
the values are all higher than 0.3 at 160 line pairs/mm (lps/mm) in the image
space. Meanwhile, stray light caused by total internal reflection on the inner
wall of the rod lenses and the objective lens is eliminated. The measured
resolution in the object space at a 20 mm working distance is 22.3 lps/mm, and
test results show that other performance characteristics also fulfill design
requirements. The relay lenses are designed with only one type of the spacer and
two types of lenses to greatly reduce the fabrication and assembly cost. The
design method has important research and application values for lens systems used
in modern minimally invasive medical surgery and industrial non-destructive
testing area.
PMID- 25136496
TI - Bone tissue phantoms for optical flowmeters at large interoptode spacing
generated by 3D-stereolithography.
AB - A bone tissue phantom prototype allowing to test, in general, optical flowmeters
at large interoptode spacings, such as laser-Doppler flowmetry or diffuse
correlation spectroscopy, has been developed by 3D-stereolithography technique.
It has been demonstrated that complex tissue vascular systems of any geometrical
shape can be conceived. Absorption coefficient, reduced scattering coefficient
and refractive index of the optical phantom have been measured to ensure that the
optical parameters reasonably reproduce real human bone tissue in vivo. An
experimental demonstration of a possible use of the optical phantom, utilizing a
laser-Doppler flowmeter, is also presented.
PMID- 25136497
TI - Measurements of extrinsic fluorescence in Intralipid and polystyrene
microspheres.
AB - The fluorescence of Intralipid and polystyrene microspheres with sphere diameter
of 1 um at a representative lipid and microsphere concentration for simulation of
mucosal tissue scattering has not been a subject of extensive experimental study.
In order to elucidate the quantitative relationship between lipid and microsphere
concentration and the respective fluorescent intensity, the extrinsic
fluorescence spectra between 360 nm and 650 nm (step size of 5 nm) were measured
at different lipid concentrations (from 0.25% to 5%) and different microsphere
concentrations (0.00364, 0.0073, 0.0131 spheres per cubic micrometer) using laser
excitation at 355 nm with pulse energy of 2.8 uJ. Current findings indicated that
Intralipid has a broadband emission between 360 and 650 nm with a primary peak at
500 nm and a secondary peak at 450 nm while polystyrene microspheres have a
single peak at 500 nm. In addition, for similar scattering properties the
fluorescence of Intralipid solutions is approximately three-fold stronger than
that of the microsphere solutions. Furthermore, Intralipid phantoms with lipid
concentrations ~2% (simulating the bottom layer of mucosa) produce up to seven
times stronger fluorescent emission than phantoms with lipid concentration ~0.25%
(simulating the top layer of mucosa). The fluoresence decays of Intralipid and
microsphere solutions were also recorded for estimation of fluorescence lifetime.
PMID- 25136499
TI - Automatic dynamic tear meniscus measurement in optical coherence tomography.
AB - An image processing algorithm is developed for quantitative assessment of tear
meniscus dynamics from continuous optical coherence tomography (OCT)
measurements. Clinical utility of dynamic OCT tear meniscus measurement is
assessed in studies of tear meniscus parameters. The results indicate that any
apparent changes in the early post-blink phase meniscus parameters are
essentially related to the longitudinal movements of the eye and not to the
formation of tear meniscus corresponding to tear film build-up. Dynamic
acquisition of tear film meniscus is essential for providing reliable estimates
of its parameters such as height, depth, and area.
PMID- 25136498
TI - Fiber-based polarization-sensitive OCT of the human retina with correction of
system polarization distortions.
AB - In polarization-sensitive optical coherence tomography (PS-OCT) the use of single
mode fibers causes unpredictable polarization distortions which can result in
increased noise levels and erroneous changes in calculated polarization
parameters. In the current paper this problem is addressed by a new Jones matrix
analysis method that measures and corrects system polarization distortions as a
function of wavenumber by spectral analysis of the sample surface polarization
state and deeper located birefringent tissue structures. This method was
implemented on a passive-component depth-multiplexed swept-source PS-OCT system
at 1040 nm which was theoretically modeled using Jones matrix calculus. High
resolution B-scan images are presented of the double-pass phase retardation,
diattenuation, and relative optic axis orientation to show the benefits of the
new analysis method for in vivo imaging of the human retina. The correction of
system polarization distortions yielded reduced phase retardation noise, and
better estimates of the diattenuation and the relative optic axis orientation in
weakly birefringent tissues. The clinical potential of the system is shown by en
face visualization of the phase retardation and optic axis orientation of the
retinal nerve fiber layer in a healthy volunteer and a glaucoma patient with
nerve fiber loss.
PMID- 25136500
TI - Speckle contrast optical spectroscopy, a non-invasive, diffuse optical method for
measuring microvascular blood flow in tissue.
AB - We introduce a new, non-invasive, diffuse optical technique, speckle contrast
optical spectroscopy (SCOS), for probing deep tissue blood flow using the
statistical properties of laser speckle contrast and the photon diffusion model
for a point source. The feasibility of the method is tested using liquid phantoms
which demonstrate that SCOS is capable of measuring the dynamic properties of
turbid media non-invasively. We further present an in vivo measurement in a human
forearm muscle using SCOS in two modalities: one with the dependence of the
speckle contrast on the source-detector separation and another on the exposure
time. In doing so, we also introduce crucial corrections to the speckle contrast
that account for the variance of the shot and sensor dark noises.
PMID- 25136501
TI - Thermally enhanced signal strength and SNR improvement of photoacoustic radar
module.
AB - A thermally enhanced method for improving photoacoustic imaging depth and signal
to-noise (SNR) ratio is presented in this paper. Experimental results showed that
the maximum imaging depth increased by 20% through raising the temperature of
absorbing biotissues (ex-vivo beef muscle) uniformly from 37 to 43 degrees C, and
the SNR was increased by 8%. The parameters making up the Gruneisen constant were
investigated experimentally and theoretically. The studies showed that the
Gruneisen constant of biotissues increases with temperature, and the results were
found to be consistent with the photoacousitc radar theory.
PMID- 25136502
TI - Single camera imaging system for color and near-infrared fluorescence image
guided surgery.
AB - Near-infrared (NIR) fluorescence imaging systems have been developed for image
guided surgery in recent years. However, current systems are typically bulky and
work only when surgical light in the operating room (OR) is off. We propose a
single camera imaging system that is capable of capturing NIR fluorescence and
color images under normal surgical lighting illumination. Using a new RGB-NIR
sensor and synchronized NIR excitation illumination, we have demonstrated that
the system can acquire both color information and fluorescence signal with high
sensitivity under normal surgical lighting illumination. The experimental results
show that ICG sample with concentration of 0.13 MUM can be detected when the
excitation irradiance is 3.92 mW/cm(2) at an exposure time of 10 ms.
PMID- 25136503
TI - Single input state polarization sensitive swept source optical coherence
tomography based on an all single mode fiber interferometer.
AB - We present a newly developed single mode fiber based swept source polarization
sensitive optical coherence tomography system using a single input state at 1040
nm. Two non-polarizing fiber based beam splitters are combined to form a Mach
Zehnder interferometer, while two polarizing beam splitters are used to obtain a
polarization sensitive detection. Both types of beam splitters solely feature
conventional single mode fibers. Polarization control paddles are used to set and
maintain the polarization states in the fibers of the interferometer and
detection unit. By use of a special paddle alignment scheme we are able to
eliminate any bulk optic wave plates and polarization maintaining fibers in the
interferometer and detection paths while preserving the advantages of a single
input state system that illuminates the sample with circularly polarized light.
To demonstrate the capabilities of our system, we performed retinal measurements
on healthy human volunteers.
PMID- 25136504
TI - Frequency-modulated light scattering interferometry employed for optical
properties and dynamics studies of turbid media.
AB - In the present work, fiber-based frequency-modulated light scattering
interferometry (FMLSI) is developed and employed for studies of optical
properties and dynamics in liquid phantoms made from Intralipid((r)). The fiber
based FMLSI system retrieves the optical properties by examining the intensity
fluctuations through the turbid medium in a heterodyne detection scheme using a
continuous-wave frequency-modulated coherent light source. A time resolution of
21 ps is obtained, and the experimental results for the diluted Intralipid
phantoms show good agreement with the predicted results based on published data.
The present system shows great potential for assessment of optical properties as
well as dynamic studies in liquid phantoms, dairy products, and human tissues.
PMID- 25136505
TI - Longitudinal vascular dynamics following cranial window and electrode
implantation measured with speckle variance optical coherence angiography.
AB - Speckle variance optical coherence angiography (OCA) was used to characterize the
vascular tissue response from craniotomy, window implantation, and electrode
insertion in mouse motor cortex. We observed initial vasodilation ~40% greater
than original diameter 2-3 days post-surgery (dps). After 4 weeks, dilation
subsided in large vessels (>50 um diameter) but persisted in smaller vessels (25
50 um diameter). Neovascularization began 8-12 dps and vessel migration continued
throughout the study. Vasodilation and neovascularization were primarily
associated with craniotomy and window implantation rather than electrode
insertion. Initial evidence of capillary re-mapping in the region surrounding the
implanted electrode was manifest in OCA image dissimilarity. Further
investigation, including higher resolution imaging, is required to validate the
finding. Spontaneous lesions also occurred in many electrode animals, though the
inception point appeared random and not directly associated with electrode
insertion. OCA allows high resolution, label-free in vivo visualization of
neurovascular tissue, which may help determine any biological contribution to
chronic electrode signal degradation. Vascular and flow-based biomarkers can aid
development of novel neural prostheses.
PMID- 25136506
TI - Study of freshly excised brain tissues using terahertz imaging.
AB - We demonstrated that tumors in freshly excised whole brain tissue could be
differentiated clearly from normal brain tissue using a reflection-type terahertz
(THz) imaging system. THz binary images of brain tissues with tumors indicated
that the tumor boundaries in the THz images corresponded well to those in visible
images. Grey and white-matter regions were distinguishable owing to the different
distribution of myelin in the brain tissue. THz images corresponded closely with
magnetic resonance imaging (MRI) results. The MRI and hematoxylin and eosin
stained microscopic images were investigated to account for the intensity
differences in the THz images for fresh and paraffin-embedded brain tissue. Our
results indicated that the THz signals corresponded to the cell density when
water was removed. Thus, THz imaging could be used as a tool for label-free and
real-time imaging of brain tumors, which would be helpful for physicians to
determine tumor margins during brain surgery.
PMID- 25136507
TI - Histology validation of mapping depth-resolved cardiac fiber orientation in fresh
mouse heart using optical polarization tractography.
AB - Myofiber organization in cardiac muscle plays an important role in achieving
normal mechanical and electrical heart functions. An imaging tool that can reveal
microstructural details of myofiber organization is valuable for both basic
research and clinical applications. A high-resolution optical polarization
tractography (OPT) was recently developed based on Jones matrix optical coherence
tomography (JMOCT). In this study, we validated the accuracy of using OPT for
measuring depth-resolved fiber orientation in fresh heart samples by comparing
directly with histology images. Systematic image processing algorithms were
developed to register OPT with histology images. The pixel-wise differences
between the two tractographic results were analyzed in details. The results
indicate that OPT can accurately image depth-resolved fiber orientation in fresh
heart tissues and reveal microstructural details at the histological level.
PMID- 25136508
TI - The potential of photoacoustic microscopy as a tool to characterize the in vivo
degradation of surgical sutures.
AB - The ex vivo and in vivo imaging, and quantitative characterization of the
degradation of surgical sutures (~500 MUm diameter) up to ~1cm depth is
demonstrated using a custom dark-field photo-acoustic microscope (PAM). A
practical algorithm is developed to accurately measure the suture diameter during
the degradation process. The results from tissue simulating phantoms and mice are
compared to ex vivo measurements with an optical microscope demonstrating that
PAM has a great deal of potential to characterize the degradation process of
surgical sutures. The implications of this work for industrial applications are
discussed.
PMID- 25136509
TI - Interspecific hybridization as a genomic stressor inducing mobilization of
transposable elements in Drosophila.
AB - Transposable elements (TEs) are DNA sequences able to be mobilized in host
genomes. They are currently recognized as the major mutation inducers because of
their insertion in the target, their effect on neighboring regions, or their
ectopic recombination. A large number of factors including chemical and physical
factors as well as intraspecific crosses have traditionally been identified as
inducers of transposition. Besides environmental factors, interspecific crosses
have also been proposed as promoters of transposition of particular TEs in plants
and different animals. Our previous published work includes a genome-wide survey
with the set of genomic TEs and shows that interspecific hybridization between
the species Drosophila buzzatii and Drosophila koepferae induces genomic
instability by transposition bursts. A high percentage of this instability
corresponds to TEs belonging to classes I and II. The detailed study of three TEs
(Osvaldo, Helena, and Galileo), representative of the different TE families,
shows an increase of transposition in hybrids compared with parental species,
that varies depending on the element. This study suggests ample variation in TE
regulation mechanisms and the question is why this variation occurs.
Interspecific hybridization is a genomic stressor that disrupts the stability of
TEs probably contributing to a relaxation of the mechanisms controlling TEs in
the Drosophila genome. In this commentary paper we will discuss these results and
the molecular mechanisms that could explain these increases of transposition
rates observed in interspecific Drosophila hybrids.
PMID- 25136510
TI - Production of therapeutic proteins in the chloroplast of Chlamydomonas
reinhardtii.
AB - Chloroplast transformation in the photosynthetic alga Chlamydomonas reinhardtii
has been used to explore the potential to use it as an inexpensive and easily
scalable system for the production of therapeutic recombinant proteins. Diverse
proteins, such as bacterial and viral antigens, antibodies and, immunotoxins have
been successfully expressed in the chloroplast using endogenous and chimeric
promoter sequences. In some cases, proteins have accumulated to high level,
demonstrating that this technology could compete with current production
platforms. This review focuses on the works that have engineered the chloroplast
of C. reinhardtii with the aim of producing recombinant proteins intended for
therapeutical use in humans or animals.
PMID- 25136511
TI - Highly conserved salt bridge stabilizes a proteinase K subfamily enzyme,
Aqualysin I, from Thermus aquaticus YT-1.
AB - The proteinase K subfamily enzymes, thermophilic Aqualysin I (AQN) from Thermus
aquaticus YT-1 and psychrophilic serine protease (VPR) from Vibrio sp. PA-44,
have six and seven salt bridges, respectively. To understand the possible
significance of salt bridges in the thermal stability of AQN, we prepared mutant
proteins in which amino acid residues participating in salt bridges common to
proteinase K subfamily members and intrinsic to AQN were replaced to disrupt the
bridges one at a time. Disruption of a salt bridge common to proteinase K
subfamily enzymes in the D183N mutant resulted in a significant reduction in
thermal stability, and a massive change in the content of the secondary structure
was observed, even at 70 degrees C, in the circular dichroism (CD) analysis.
These results indicate that the common salt bridge Asp183-Arg12 is important in
maintaining the conformation of proteinase K subfamily enzymes and suggest the
importance of proximity between the regions around Asp183 and the N-terminal
region around Arg12. Of the three mutants that lack an AQN intrinsic salt bridge,
D212N was more prone to unfolding at 80 degrees C than the wild-type enzyme.
Similarly, D17N and E237Q were less thermostable than the wild-type enzyme,
although this may be partially due to increased autolysis. The AQN intrinsic salt
bridges appear to confer additional thermal stability to this enzyme. These
findings will further our understanding of the factors involved in stabilizing
protein structure.
PMID- 25136512
TI - Imaging of alpha7 nicotinic acetylcholine receptors in brain and cerebral
vasculature of juvenile pigs with [(18)F]NS14490.
AB - BACKGROUND: The alpha7 nicotinic acetylcholine receptor (nAChR) is an important
molecular target in neuropsychiatry and oncology. Development of applicable
highly specific radiotracers has been challenging due to comparably low protein
expression. To identify novel ligands as candidates for positron emission
tomography (PET), a library of diazabicyclononane compounds was screened
regarding affinity and specificity towards alpha7 nAChRs. From these,
[(18)F]NS14490 has been shown to yield reliable results in organ distribution
studies; however, the radiosynthesis of [(18)F]NS14490 required optimization and
automation to obtain the radiotracer in quantities allowing dynamic PET studies
in piglets. METHODS: Automated radiosynthesis of [(18)F]NS14490 has been
performed by [(18)F]fluorination with the tosylate precursor in the TRACERlabTM
FX F-N synthesis module (Waukesha, WI, USA). After optimization, the
radiochemical yield of [(18)F]NS14490 was consistently approximately 35%, and the
total synthesis time was about 90 min. The radiotracer was prepared with >92%
radiochemical purity, and the specific activity at the end of the synthesis was
226 +/- 68 GBq MUmol(-1). PET measurements were performed in young pigs to
investigate the metabolic stability and cerebral binding of [(18)F]NS14490
without and with administration of the alpha7 nAChR partial agonist NS6740 in
baseline and blocking conditions. RESULTS: The total distribution volume relative
to the metabolite-corrected arterial input was 3.5 to 4.0 mL g(-1) throughout the
telencephalon and was reduced to 2.6 mL g(-1) in animals treated with NS6740.
Assuming complete blockade, this displacement indicated a binding potential
(BPND) of approximately 0.5 in the brain of living pigs. In addition, evidence
for specific binding in major brain arteries has been obtained. CONCLUSION:
[(18)F]NS14490 is not only comparable to other preclinically investigated PET
radiotracers for imaging of alpha7 nAChR in brain but also could be a potential
PET radiotracer for imaging of alpha7 nAChR in vulnerable plaques of diseased
vessels.
PMID- 25136514
TI - 4D PET/CT as a Strategy to Reduce Respiratory Motion Artifacts in FDG-PET/CT.
AB - The improved accuracy in tumor identification with FDG-PET has led to its
increased utilization in target volume delineation for radiotherapy treatment
planning in the treatment of lung cancer. However, PET/CT has constantly been
influenced by respiratory motion-related image degradation, which is especially
prominent for small lung tumors in the peri-diaphragmatic regions of the thorax.
Here, we describe the current findings on respiratory motion-related image
degradation in PET/CT, which may bring uncertainties to target volume delineation
for image guided radiotherapy (IGRT) for lung cancer. Furthermore, we describe
the evidence suggesting 4D PET/CT to be one strategy to minimize the impact of
respiratory motion-related image degradation on tumor target delineation for
thoracic IGRT. This, in our opinion, warrants further investigation in future
IGRT-based lung cancer trials.
PMID- 25136513
TI - Genetically engineered mouse models of pituitary tumors.
AB - Animal models constitute valuable tools for investigating the pathogenesis of
cancer as well as for preclinical testing of novel therapeutics approaches.
However, the pathogenic mechanisms of pituitary-tumor formation remain poorly
understood, particularly in sporadic adenomas, thus, making it a challenge to
model pituitary tumors in mice. Nevertheless, genetically engineered mouse models
(GEMMs) of pituitary tumors have provided important insight into pituitary tumor
biology. In this paper, we review various GEMMs of pituitary tumors, highlighting
their contributions and limitations, and discuss opportunities for research in
the field.
PMID- 25136515
TI - Drug-diagnostics co-development in oncology.
PMID- 25136517
TI - Head and neck cancers: Safely preserving the talk.
PMID- 25136518
TI - Pathology of radiation toxicity and its implication on quality of life.
PMID- 25136516
TI - Induction of endoplasmic reticulum stress and unfolded protein response
constitutes a pathogenic strategy of group A streptococcus.
AB - The connection between bacterial pathogens and unfolded protein response (UPR) is
poorly explored. In this review we highlight the evidence showing that group A
streptococcus (GAS) induces endoplasmic reticulum (ER) stress and UPR through
which it captures the amino acid asparagine (ASN) from the host. GAS acts
extracellularly and during adherence to host cells it delivers the hemolysin
toxins; streptolysin O (SLO) and streptolysin S (SLS). By poorly understood
pathways, these toxins trigger UPR leading to the induction of the
transcriptional regulator ATF4 and consequently to the upregulation of asparagine
synthetase (ASNS) transcription leading to production and release of ASN. GAS
senses ASN and alters gene expression profile accordingly, and increases the rate
of multiplication. We suggest that induction of UPR by GAS and by other bacterial
pathogens represent means through which bacterial pathogens gain nutrients from
the host, obviating the need to become internalized or inflict irreversible cell
damage.
PMID- 25136520
TI - Genetically altered fields in head and neck cancer and second field tumor.
AB - The concept of field cancerization has been ever changing since its first
description by Slaughter et al in 1953. Field cancerization explains the
mechanisms by which second primary tumors (SPTs) develop. SPTs are the tumors,
which develop in the oral cavity in succession to the primary malignant tumors,
which might vary in duration ranging from few months to years. Conceivably, a
population of daughter cells with early genetic changes (without histopathology)
remains in the organ, demonstrating the concept of field cancerization. This
review explains the concept of field cancerization and various field theories
along with molecular basis of field formation.
PMID- 25136521
TI - Association of cytochrome P450 2C9 polymorphism with locally advanced head and
neck squamous cell carcinoma and response to concurrent cisplatin-based radical
chemoradiation.
AB - AIMS: The aim of the present study is to investigate the association between
polymorphism of cytochrome P450 2C9 (CYP2C9) enzyme with head and neck squamous
cell carcinoma (HNSCC) and response in patients receiving cisplatin-based radical
chemoradiation (CT-RT). MATERIALS AND METHODS: Four hundred and sixty patients
suffering from locally advanced HNSCC and an equal number of healthy controls
were genotyped for CYP2C9*2 and CYP2C9*013, leading to poor metabolizers (PMs) by
polymerase chain reaction (PCR)-based restriction fragment length polymorphism
(RFLP). Each case was assessed thoroughly for treatment response as per the World
Health Organization (WHO) criteria. RESULTS AND ANALYSIS: The frequency of
heterozygous genotypes of both CYP2C9*2 (27.8%) and CYP2C9*3 (25%) were found to
be significantly higher in the HNSCC cases as compared to the healthy controls.
Tobacco intake in the form of chewing or smoking and alcohol intake resulted in
several folds increase in the risk to HNSCC in the cases carrying variant
genotypes of CYP2C9*2 or CYP2C9*013. Further, majority of the cases assessed for
response (n = 436) carrying variant alleles of CYP2C9*2 (69.6%) or CYP2C9*3
(65.2%) were found to respond poorly to cisplatin-based radical CT-RT.
CONCLUSION: The data suggests a significant association of the CYP2C9
polymorphism with HNSCC and treatment outcome underlining the importance of
pretherapeutic genotyping in determining the treatment protocol.
PMID- 25136519
TI - Organ preservation strategies: Review of literature and their applicability in
developing nations.
AB - There has been a change in practice in locally advanced laryngopharyngeal cancers
toward non-surgical treatment modalities. Although, there have been landmark
trials pertinent to organ preservation, their applicability in developing nations
is a topic of much debate. The organ preservation concept was based on the
findings of pivotal trials by the Veterans Affairs, European Organization for
Research and Treatment of Cancer group and Radiation Therapy Oncology Group.
Subsequently numerous studies have been designed to evaluate intensification of
treatment as well as study toxicity and tolerability. This review critically
analyses current evidence for larynx preservation, experience from various
centers on organ preservation strategies as well as applicability of these
protocols to developing nations.
PMID- 25136522
TI - Post-radiation changes in oral tissues - An analysis of cancer irradiation cases.
AB - INTRODUCTION: Radiation, commonly employed as neoadjuvant, primary, and adjuvant
therapy for head and neck cancer causes numerous epithelial and stromal changes,
prominent among which is fibrosis with its early and late consequences. Very
little is known about the true nature of the fibrosed tissue and the type of
fibers accumulated. Radiotherapy affects the supporting tumor stroma often
resulting in a worsening grade of tumor post-radiation. AIM: To study epithelial,
neoplastic, stromal, and glandular changes in oral cavity induced by radiation
therapy for oral squamous cell carcinoma (OSCC) using special stains. MATERIALS
AND METHODS: The study included 27 samples of recurrent OSCC following completion
of radiotherapy (recurrence within an average span of 11 months), and 26 non
irradiated cases of OSCC. Patients with a history of combined radiotherapy and
chemotherapy were not included in the study. The epithelial changes assessed
included epithelial atrophy, apoptosis, necrosis, dysplasia, and neoplasia. The
connective tissue was evaluated for amount of fibrosis, quality of fibers (using
picrosirius red staining), fibrinous exudate, necrosis, pattern of invasion,
vessel wall thickening, and salivary gland changes. The aforementioned changes
were assessed using light and polarizing microscopy and tabulated. STATISTICAL
ANALYSIS: Epithelial and connective tissue parameters were compared between the
irradiated and non-irradiated cases using chi square and t-tests. RESULTS:
Epithelial and connective tissue parameters were found to be increased in
irradiated patients. Pattern of invasion by tumor cells varied from strands and
cords between the two groups studied. The effect of radiation was seen to reflect
on the maturity of fibers and the regularity of their distribution.
PMID- 25136523
TI - Survival outcome of malignant minor salivary tumors in Pakistani population.
AB - OBJECTIVE: Malignant tumors of minor salivary glands (MSG) are rare. Survival
outcome in Pakistani population with malignant MSG tumors remains to be defined.
The objective of this study was to report the clinical presentation, treatment
modalities, and survival outcome of radically treated malignant tumors of MSG in
Pakistani population. MATERIALS AND METHODS: Between April 2003 and March 2011,
45 patients with malignant tumors of MSG were treated at Shaukat Khanum Cancer
Hospital and included in the study. Patient characteristics and treatment
modalities were assessed and local, regional, and distant failures determined.
Relapse-free (RFS) and overall survival (OS) was calculated using Kaplan-Meier
curves, and log-rank test was used to determine significance. RESULTS: Median age
was 40 (17-83) years. Male to female ratio was 1.25:1. Most common site was hard
palate in 31 (69%) patients. Adenoid cystic carcinoma (51%) was the most common
histological diagnosis. Nine patients (20%) underwent surgery as the only
treatment modality, six patients received (13%) radiotherapy alone, and 30
patients (67%) had surgery followed by adjuvant radiotherapy. Eight patients
developed recurrence (four local, two regional, one locoregional, and one
distant). The 5-year actuarial overall OS and RFS was 77 and 66%, respectively.
Age, T-stage, and treatment modality were significant for RFS, whereas T-stage
and treatment modality were significant factors for OS. CONCLUSION: Surgery as
single modality or combined with radiation therapy resulted in acceptable
survival in Pakistani population with malignant minor salivary tumors.
PMID- 25136524
TI - Palliative low dose fortnightly methotrexate in oral cancers: Experience at a
rural cancer centre from India.
AB - CONTEXT: Palliative fortnightly chemotherapy in oral cancers. AIMS: We present
our experience with a regimen employing fortnightly (once in 2 weeks) injectable
methotrexate (MTX) (40 mg/m(2) ) in a predominantly elderly cohort of patients
with carcinoma of oral cavity and oropharynx. SETTINGS AND DESIGN: Retrospective
chart review conducted at a rural cancer center in India. MATERIALS AND METHODS:
All patients with oral cavity and oropharyngeal cancers started on treatment with
fortnightly injectable MTX (40 mg/m(2) ) between 01/01/2011 and 31/12/2011.
STATISTICAL ANALYSIS USED: The factors analyzed included the duration of disease
control, pain control, overall survival and progression free survival which were
evaluated using the Kaplan Meier method. RESULTS: A total of 60 patients with a
median age of 66.5 years were analyzed. Majority of the patients had poor
nutritional status, performance status or co-morbidities. MTX was given for
recurrent disease in 19 patients and after initial palliative radiotherapy in 41
patients. The median number of cycles delivered was nine. Grade 3/4 toxicities
were seen in 2 patients only. Disease control rate at the end of treatment was
seen in 33 (55%) patients. Median overall survival was 34 weeks (interquartile
range: 17-50 weeks). CONCLUSIONS: The fortnightly regimen of MTX was well
tolerated and showed a good clinical activity in this elderly cohort of patients
with advanced oral cavity and oropharyngeal cancers.
PMID- 25136525
TI - Relationship of angiogenic and apoptotic activities in soft-tissue sarcoma.
AB - INTRODUCTION: Angiogenesis and apoptosis play an essential role in tumor
development and progression. Previous studies on apoptosis and angiogenesis of
soft-tissue sarcoma (STS) were done separately. This is the first study of the
relationship between apoptotic and angiogenic activity. Correlation of expression
of anti-apoptotic protein (Bcl-2) and pro-apoptotic protein (Bax) in the tumor
cells (TCs) with their expression in endothelial cell (EC) of the tumor blood
vessels in STS were also carried out. MATERIALS AND METHODS: 101 cases of STS;
consisting liposarcoma, malignant fibrous histiocytoma, synovial sarcoma,
fibrosarcoma, leiomyosarcoma, rhabdomyosarcoma and malignant peripheral nerve
sheath tumor; were collected and immunohistochemical reaction of vascular
endothelial growth factor (VEGF), Bcl-2 and Bax were examined. RESULTS: Higher
Bax expression in TCs (54.5%) was seen compared to Bcl-2 expression (44.6%).
There was a significant association between Bcl-2 and Bax in TCs with ECs.
Significant association was also seen between histological types of STS with Bcl
2 expression; however not with Bax expression. There was an association between
VEGF and Bax with high VEGF expression and weak Bax expression. However, VEGF
expression was not associated with Bcl-2 expression and histological types.
CONCLUSION: This study supports the role of ECs of tumor blood vessels and
apoptosis of TCs in tumor management. Increased angiogenesis may inhibit
apoptosis of TCs and lead to tumor growth. Therefore, inhibition of ECs survival
or activation of ECs death is promising prospect for tumor therapy.
Immunohistochemical antibodies in this study might be potential useful marker for
the prognosis of STS.
PMID- 25136526
TI - Biweekly cetuximab and first-line chemotherapy in chinese patients with k-ras
wild-type colorectal cancers.
AB - BACKGROUND: The efficacy and safety of using combination chemotherapy with
cetuximab as first-line treatment in patients with K-ras wild-type colorectal
cancers has been well established. In general, weekly cetuximab was given with
biweekly chemotherapy FOLFOX-4 or FOLFIRI, synchronizing them would be appealed
to both patients and health care professionals. MATERIALS AND METHODS: This Phase
II, prospective study investigated the efficacy and safety of using biweekly
cetuximab 500 mg/m(2) with chemotherapy FOLFOX-4 or FOLFIRI as first-line
treatment for Chinese patients with K-ras wild-type metastatic colorectal cancer.
The study endpoints included overall objective response (OR), progression-free
survival (PFS), overall survival (OS) and safety. RESULTS: Total 15 Chinese
patients (male: 10 [67%]; median age: 60 [range 41-80]) were enrolled. Patients
received median 12 cycles (range 2-12) of chemotherapy + cetuximab (FOLFOX-4 +
cetuximab: 9 [60%]; FOLFIRI + cetuximab: 6 [40%]). Six patients (40%) with non
progressive disease after 12 cycles of chemotherapy + cetuximab carried on
maintenance cetuximab. Median duration of follow-up (FU) was 23.7 months. The OR
was 40% (complete response: 0%; partial response: 40%) for a disease control rate
of 87%. Median PFS and OS were 7.8 months and 17.9 months respectively. For
maintenance cetuximab phase, median PFS since the start of maintenance cetuximab
was 6.8 months and median OS was 17.0 months. The only grade 3-4 toxicities were
neutropenia (26.7%) in chemotherapy phase and acneiform rashes (16.7%) in
maintenance phase. CONCLUSIONS: Biweekly cetuximab with combination chemotherapy
was effective and safe as weekly dose. Further studies are warranted for the role
of maintenance cetuximab.
PMID- 25136527
TI - A retrospective study of clinico-pathological spectrum of carcinoma breast in a
West Delhi, India.
AB - BACKGROUND: Data on the demographic profile of breast cancer patients from Delhi
is scarce and whatever is available is from higher referral center. Our hospital
caters to patients from an urban population of the lower socioeconomic strata and
is a representation of cases at a tertiary care hospital in west Delhi. In Delhi,
breast cancer (26.8%) is commonest cancer among the female followed by cervix
(12.5%), gallbladder (7.2%), ovary (7.1%), and uterus (3.3%). AIMS AND
OBJECTIVES: A retrospective audit of breast cancer patients presenting at a
tertiary referral center from 2004 to 2011. MATERIALS AND METHODS: A total of 328
cases diagnosed as carcinoma breast on histopathology from year 2004 to 2011 were
retrieved and studied retrospectively with regards to demographic profile and
their histological features with estrogen receptor (ER), progesterone receptor
(PR), and Her2neu status. RESULTS: The median age of presentation was 49 years of
age. Infiltrating ductal carcinoma (IDC, not otherwise specified (NOS)) was the
commonest histopathological variant (81.40%) followed by medullary carcinoma
(10.36%) and mucinous carcinoma (2.74%). Triple negative were found to be the
commonest group comprising 39.4% of all the cases followed by ER and PR both
positive. Pathological tumor, node, and metastasis (TNM) staging showed most
common group was T2N0M0 (19.5%) followed by T2N1M0 (17.1%) and T2N2M0 (14%).
CONCLUSION: The incidence of breast cancer in the India and include a higher
incidence of ER, PR, and Her2neu negative disease in west Delhi.
PMID- 25136528
TI - Tolvaptan.
AB - Hyponatremia is a common and often under-recogonised clinical problem in
oncologic practice. The recogonition of the cause of hyponatremia and initiation
of appropriate and timely intervention can prevent morbidity and improve
treatment tolerance. This drug review aims at discussing the currently approved
oral vaptanagent Tolvaptan. Vaptans including Tolvaptan act as "aquaretic" agents
cousing excretion of water while retaining the sodium. Administration of this
agent for prescribed periods result in improvement of serum sodium levels. The
drug can be used in many clinical situations resulting in hyponatremia including
congestive heart failure, cirrhosis and syndrome of inappropriate ADH secretion
(SIADH) including SIADH related to malignancies.
PMID- 25136529
TI - Radiation stents: Minimizing radiation-induced complications.
PMID- 25136530
TI - Waste landfill site fire crisis in Thailand; sulfur dioxide pollution and
estimation of cancer risk.
PMID- 25136531
TI - Diffuse large B-cell lymphoma in patients with chronic lymphocytic leukemia: A
single center experience.
PMID- 25136532
TI - Giant anterior ameloblastoma managed by wide excision mandibulectomy with
intraoral primary mucosal closure and skin defect coverage by deltopectoral flap.
PMID- 25136533
TI - Shewanella algae: First case report of the fast emerging marine pathogen from
squamous cell carcinoma patient in India.
PMID- 25136534
TI - Expected efficacy of HPV vaccine in prevention of cervix cancer in Thailand.
PMID- 25136535
TI - Dietary factors and the risk of thyroid cancer: a review.
AB - In the past few decades, the incidence of thyroid cancer has rapidly increased
worldwide. Thyroid cancer incidence is relatively high in regions where the
population's daily iodine intake is insufficient. While low dietary iodine has
been considered as a risk factor for thyroid cancer development, previous studies
found controversial results across different food types. Among different ethnic
groups, dietary factors are influenced by various dietary patterns, eating
habits, life-styles, nutrition, and other environmental factors. This review
reports the association between dietary factors and thyroid cancer risk among
ethnic groups living in different geologic regions. Iodine-rich food such as fish
and shellfish may provide a protective role in populations with insufficient
daily iodine intake. The consumption of goitrogenic food, such as cruciferous
vegetables, showed a positive association with risk. While considered to be a
risk factor for other cancers, alcohol intake showed a protective role against
thyroid cancer. High consumption of meat such as chicken, pork, and poultry
showed a positive association with the risk, but dairy products showed no
significant association. Regular use of multivitamins and dietary nitrate and
nitrite also showed a positive association with thyroid cancer risk. However, the
study results are inconsistent and investigations into the mechanism for how
dietary factors change thyroid hormone levels and influence thyroid function are
required.
PMID- 25136536
TI - Effects of Korean White Ginseng (Panax Ginseng C.A. Meyer) on Vascular and
Glycemic Health in Type 2 Diabetes: Results of a Randomized, Double Blind,
Placebo-controlled, Multiple-crossover, Acute Dose Escalation Trial.
AB - Korean red ginseng (steam treated Panax ginseng C.A. Meyer), among most prized
traditional herbal remedies, has been clinically shown to improve cardiovascular
disease (CVD) risk factors. Whether this holds true for the dried non-steamed
variety, known as Korean white ginseng (KWG) is unclear. This study therefore,
investigated the efficacy and safety of escalating doses of KWG on vascular and
glycemic parameters in type 2 diabetes (T2DM). Using an acute, randomized,
placebo-controlled, double-blind, crossover design, 25 participants with well
controlled T2DM (12-males: 13-females, age: 63 +/- 9 years, A1c: 6.9 +/- 0.7%,
BMI: 29.3 +/- 4.3 kg/m(2)) underwent five visits during which they received 1 g,
3 g, or 6 g KWG or 3 g wheat-bran control (twice) together with 50 g-glucose
load. For the duration of 240 minutes, augmentation index (AI), and central blood
pressure were measured at baseline and at 60 min-intervals, and ambulatory blood
pressure was assessed at baseline and at 10 min-intervals. Additionally,
capillary blood was collected at time zero and at 15, 30, 45, 60, 90, 120, and
180 minutes post-treatment. A symptoms questionnaire was used to assess safety
and adverse events. Two-way ANOVA demonstrated a significant time-treatment
interaction effect on AI (p = 0.01) with one-way ANOVA showing significant
reductions in AI with 3 g KWG relative to control (p = 0.04). Compared to
control, acute administration of KWG appeared to be safe, but did not affect any
other postprandial, vascular or glycemic parameters. KWG might have a beneficial
effect on AI, a cumulative indicator of arterial health. However, these results
are preliminary and highlight the need for long-term investigation with a focus
on its accountable components. CLINICAL TRIAL REGISTRATION: NCT01699074.
PMID- 25136537
TI - Immunomodulatory effects of kimchi in chinese healthy college students: a
randomized controlled trial.
AB - This study examined the potential immunomodulatory effects of Kimchi, a
traditional fermented Korean vegetable, in healthy Chinese college students. The
four-week clinical-trial (randomized, open-label, prospective, controlled) was
followed by a one week wash-out period. Healthy Chinese college students (over 20
years of age with a body mass index of 18.5-23.0 kg/m(2)) volunteered for this
study. Forty-three students were randomly classified into two groups, Kimchi (n =
21, supplemented with 100 g of Kimchi per day) or non-Kimchi (n = 22,
supplemented with 100 g of radish per day, control) groups. During the four-week
intervention period, students were asked to maintain their usual diet and
activity, and instructed not to take any medications, functional food products,
or dietary supplements. Anthropometrics, nutritional intake, and blood immune
parameters (lymphocyte subsets, cytokines, and immunoglobulins) were measured
before and after the four weeks of intervention. Thirty-nine students (19 in the
Kimchi group, 20 in the non-Kimchi group) finished the study. After the
intervention, no significant changes were observed in lymphocyte subsets (T-cell,
B-cell, NK cell), pro-inflammatory cytokines (IL-6, TNF-alpha), anti-inflammatory
cytokines (IL-4 and IL-10), and immunoglobulins (Ig A, G, and M) between groups
in either the Kimchi or non-Kimchi. These results suggest that the short-term
consumption of Kimchi has no immunomodulatory effects in healthy Chinese college
students.
PMID- 25136538
TI - Effects of diet modification on meal quality and quality of life in korean
diabetic patients: data from Korea national health and nutrition examination
survey (2007-2011).
AB - It is generally accepted that diet modification provides beneficial effects on
the management of diabetes. In the present study, we evaluated the effects of
diet modification on nutrient intake and quality of life in a large sample of
diabetic patients. This study was conducted using data from the Korea National
Health and Nutrition Examination Survey IV and V (2007-2010). A total of 2,484 of
diabetic patients were included in the analysis. Then, we compared the overall
quality of dietary intake between diabetic patients with diet modification and
those without dietary modification. The result showed that subjects on diabetic
diet (DDG) showed lower levels of total cholesterol, triglyceride, and AST before
and after the adjustment for covariates (all p < 0.05). The results of nutrient
assessment showed that DDG had lower intakes of total energy, fat, and
carbohydrate (all p < 0.05), but higher intakes of energy from protein, vitamin
B1, vitamin B2, niacin and vitamin C than NDG. (all p < 0.05). In addition,
nutritional adequacy ratio of calcium and vitamin B2 were significantly higher in
DDG than those in normal diet group (NDG) (p < 0.05). However, we observed no
significant differences in quality of life between two groups. In conclusion,
diet modification in diabetic patients seemed to be effective to improve blood
lipid profile and the adequacy of nutrient intake without sacrificing the quality
of life.
PMID- 25136539
TI - Development and Evaluation of a Web-based Computer-Assisted Personal Interview
System (CAPIS) for Open-ended Dietary Assessments among Koreans.
AB - The accuracy of dietary assessments has emerged as a major concern in nutritional
epidemiology and new dietary assessment tools using computer technology to
increase accuracy have been developed in many countries. The purpose of this
study was to develop a web-based computer-assisted personal interview system
(CAPIS) for conducting dietary assessment and to evaluate its practical
utilization among Koreans. The client software was developed using Microsoft's
ClickOnce technology, which allows communication with a database system via an
http server to add or retrieve data. The system consists of a tracking system for
the subject and researcher, a data-input system during the interview, a
calculation system for estimating food and nutrient intake, a data-output system
for presenting the results, and an evaluation system for assessing the adequacy
of nutrient and food intake. Databases of the nutrient composition of common food
(n = 3,642), recipes for common dishes (n = 1,886), and photos of serving sizes
for food and dishes (n = 4,152) were constructed, and logical processes for data
collection, calculation, and output were developed. The functionality, on-site
applicability, and efficiency of CAPIS were evaluated in a convenience sample of
181 participants (61 males, 120 females; aged 24 to 85) by comparing with manual
24 hour recall method with paper questionnaire. The CAPIS was functioned
adequately in the field survey in terms of completeness of function, security,
and compliance of researcher and subjects. Regarding on-site applicability,
23.2%, 32.6%, 35.4%, and 43.7% of subjects reported that CAPIS was easier to
recall their diet, to estimate the amount consumed, to communicate with the
interviewer, and to concentrate on the interview than the manual method with
paper questionnaire, respectively. Although CAPIS required more interview time (9
min 42 sec) compared to the manual method (7 min 30 sec), it saved time and cost
for data coding and entry (15 min 35 sec) and gave high satisfaction from the
prompt feedback after interview to the subjects, which increase efficiency to
apply on the field survey. Our results suggest that the newly developed CAPIS is
suitable for conducting personal interviews for dietary assessment in Korean
population.
PMID- 25136540
TI - Evaluation of fruit intake and its relation to body mass index of adolescents.
AB - Diets high in fruits and vegetables are recommended to maintain health. However,
accurate fruit intake evaluation is hard and high sugar content in most of the
fruits suggest possible negative relationships with health indices. The purpose
of the present study was to evaluate the fruit intake status of adolescents and
to examine the relationship between fruit intake and body mass index (BMI). For
this, 400 middle and high school students were surveyed for their fruit eating
attitude, preference, and intake level for fruit along with the evaluation of
their relationship with anthropometric measures. As for fruit preference, the
most frequent answer was 'like very much' (60.0%) and the preference of fruit was
significantly higher in females than in males (p < 0.01). The highest answer to
the reason to like fruits was 'delicious' (67.0%). The highest proportion of
subjects replied that the amount of fruit intake was similar in both school meals
and at home (39.3%) and unlikable feeling of fruits was 'sour' (47.0%). The
favorite fruit was the apple followed by oriental melon, grape, Korean cherry,
cherry, tangerine/orange, hallabong, plum, mango, persimmon, peach, pear/kiwi,
apricot, Japanese apricot, and fig in order. As for the number of serving sizes
per person were 2.9 times/day for male students and 3.0 times/day for female
students showing no significant difference. The frequency of eating fruits in the
evening showed a significant positive correlation with body weight (p < 0.05) and
BMI (p < 0.01), respectively. In summary of these study findings, it was found
that the fruit preference of adolescents was relatively high and their fruit
intake level satisfied the recommended number of intake. The number of evening
fruit intake had a significantly positive correlation with body weight and BMI.
Further studies are required to examine the relationship between fruit intake and
health indicators.
PMID- 25136541
TI - Coffee enema for preparation for small bowel video capsule endoscopy: a pilot
study.
AB - Coffee enemas are believed to cause dilatation of bile ducts and excretion of
bile through the colon wall. Proponents of coffee enemas claim that the cafestol
palmitate in coffee enhances the activity of glutathione S-transferase, an enzyme
that stimulates bile excretion. During video capsule endoscopy (VCE), excreted
bile is one of the causes of poor preparation of the small bowel. This study
aimed to evaluate the feasibility and effect of coffee enema for preparation of
the small bowel during VCE. In this pilot study, 17 of 34 patients were assigned
to the coffee enema plus polyethylene glycol (PEG) 2 L ingestion group, whereas
the 17 remaining control patients received 2 L of PEG only. The quality of bowel
preparation was evaluated in the two patient groups. Bowel preparations in the
proximal segments of small bowel were not differ between two groups. In the mid
and distal segments of the small intestine, bowel preparations tend to be better
in patients who received coffee enemas plus PEG than in patients who received PEG
only. The coffee enema group did not experience any complications or side
effects. Coffee enemas may be a feasible option, and there were no clinically
significant adverse events related to coffee enemas. More prospective randomized
studies are warranted to improve small bowel preparation for VCE.
PMID- 25136542
TI - Compromised Diet Quality is Associated with Decreased Renal Function in Children
with Chronic Kidney Disease.
AB - Nutritional status of children with chronic kidney disease (CKD) is important
since it affects growth and development. This study was to investigate overall
diet quality measured by nutrient intake adequacy, nutrient density, and several
dietary habits in children with CKD and its relationship with clinical parameters
according to glomerular filtration rate (GFR). Assessment of nutritional status
and diet quality was conducted in nineteen children with CKD. Average Z-scores of
height, weight and body mass index (BMI) in the participants were less than
standard growth rate. Nutritional status, such as Z-scores of height (p < 0.05)
and serum total protein (p < 0.05), were significantly lower in the children with
GFR < 75 mL/min/1.73 m(2) compared to those with GFR >= 75 mL/min/1.73 m(2).
Nutrition adequacy ratio of energy, thiamin, riboflavin, vitamin B6, folate,
iron, and zinc and overall diet quality were significantly poorer in the children
with GFR < 75 mL/min/1.73 m(2). Poorer appetite and avoidance of food were
observed in the children with higher blood urea nitrogen (BUN). Intakes of iron,
zinc, thiamin, niacin, and vitamin B6 were positively correlated with GFR.
Intakes of calcium, potassium and folate were positively correlated with BUN,
while protein intakes were negatively correlated. Overall nutrient intakes were
inadequate and diet quality was decreased as kidney function was decreased.
Dietary habit and appetite were also related with kidney function in this study
subjects. Systemic efforts of nutritional intervention are imperative to prevent
deteriorating growth and development and improve the nutritional status in
children with CKD.
PMID- 25136543
TI - Medical Nutrition Therapy based on Nutrition Intervention for a Patient with
Chronic Obstructive Pulmonary Disease.
AB - Chronic obstructive pulmonary disease (COPD) is a major cause of disability, and
according to statistics from the World Health Organization, COPD is the fourth
leading cause of death overall in the face of decades, and expected to be
increased. In 2005, the reported prevalence of COPD in Korea was 17.2% of adults
over the age of 45. Malnutrition is a common problem in papatients with COPD. And
several nutritional intervention studies showed a significant improvement in
physical and functional outcomes. According to the results of previous studies,
the nutritional support is important. This is a case report of a patient with
COPD who was introduced to a proper diet through nutrition education based on the
medical nutrition therapy protocol for COPD.
PMID- 25136544
TI - Changes in fat intake, body fat composition and intra-abdominal fat after
bariatric surgery.
AB - Bariatric surgery is considered to be the effective treatment alternative
conducted over the lifetime for reducing weight in patients with clinically
morbid obesity. For many patients, the benefits of weight loss, including
decreases in blood glucose, lipids, and blood pressure as well as increase in
mobility, will outweigh the risks of surgical complications. But patients
undergoing bariatric surgery have the least risk for long-term diet-related
complications as reported in several studies. Thus, with an increasing number of
severely obese patients undergoing bariatric surgery, the multidisciplinary
healthcare system will need to be managed continuously. Many nutrition support
specialists will need to become familiar with the metabolic consequences for the
frequent monitoring of nutrition status of the patients. South Korea has a very
short history with bariatric surgery, and relatively few studies have been
conducted on bariatric surgery. Therefore, the objective of this report was to
compare the nutrient intake, weight loss, body fat composition, and visceral fat
before and after the bariatric surgery.
PMID- 25136545
TI - Reducing auditory hypersensitivities in autistic spectrum disorder: preliminary
findings evaluating the listening project protocol.
AB - Auditory hypersensitivities are a common feature of autism spectrum disorder
(ASD). In the present study, the effectiveness of a novel intervention, the
listening project protocol (LPP), was evaluated in two trials conducted with
children diagnosed with ASD. LPP was developed to reduce auditory
hypersensitivities. LPP is based on a theoretical "neural exercise" model that
uses computer altered acoustic stimulation to recruit the neural regulation of
middle ear muscles. Features of the intervention stimuli were informed by basic
research in speech and hearing sciences that has identified the specific acoustic
frequencies necessary to understand speech, which must pass through middle ear
structures before being processed by other components of the auditory system. LPP
was hypothesized to reduce auditory hypersensitivities by increasing the neural
tone to the middle ear muscles to functionally dampen competing sounds in
frequencies lower than human speech. The trials demonstrated that LPP, when
contrasted to control conditions, selectively reduced auditory
hypersensitivities. These findings are consistent with the polyvagal theory,
which emphasizes the role of the middle ear muscles in social communication.
PMID- 25136546
TI - Focus on apoptosis to decipher how alcohol and many other drugs disrupt brain
development.
PMID- 25136547
TI - Developing a Dissemination Model to Improve Intervention Reach among West
Virginia Youth Smokers.
AB - The not-on-tobacco program is an evidence-based teen smoking cessation program
adopted by the American Lung Association (ALA). Although widely disseminated
nationally via ALA Master Trainers, in recent years, adoption and implementation
of the N-O-T program in West Virginia (WV) has slowed. WV, unfortunately, has one
of the highest smoking rates in the US. Although it is a goal of public health
science, dissemination of evidence-based interventions is woefully understudied.
The present manuscript reviews a theoretical model of dissemination of the not-on
tobacco program in WV. Based on social marketing, diffusion of innovations, and
social cognitive theories, the nine-phase model incorporates elements of
infrastructure development, accountability, training, delivery, incentives, and
communication. The model components as well as preliminary lessons learned from
initial implementation are discussed.
PMID- 25136548
TI - Biosecurity Policy in the US: A Critical Assessment.
PMID- 25136549
TI - Polycyclic aromatic compounds as anticancer agents: synthesis and biological
evaluation of methoxy dibenzofluorene derivatives.
AB - Synthesis of a new methoxy dibenzofluorene through alkylation, cyclodehydration
and aromatization in a one-pot operation is achieved for the first time. Using
this hydrocarbon, a few derivatives are prepared through aromatic nitration,
catalytic hydrogenation, coupling reaction with a side chain and reduction. The
benzylic position of this hydrocarbon with the side chain is oxidized and
reduced. Some of these derivatives have demonstrated excellent antitumor
activities in vitro. This study confirms antitumor activity depends on the
structures of the molecules.
PMID- 25136550
TI - Effects of a pragmatic lifestyle intervention for reducing body mass in obese
adults with obstructive sleep apnoea: a randomised controlled trial.
AB - This study investigated the effects of a pragmatic lifestyle intervention in
obese adults with continuous positive airway pressure-treated obstructive sleep
apnoea hypopnoea syndrome (OSAHS). Sixty patients were randomised 1 : 1 to either
a 12-week lifestyle intervention or an advice-only control group. The
intervention involved supervised exercise sessions, dietary advice, and the
promotion of lifestyle behaviour change using cognitive-behavioural techniques.
Outcomes were assessed at baseline (week 0), intervention end-point (week 13),
and follow-up (week 26). The primary outcome was 13-week change in body mass.
Secondary outcomes included anthropometry, blood-borne biomarkers, exercise
capacity, and health-related quality of life. At end-point, the intervention
group exhibited small reductions in body mass (-1.8 [-3.0, -0.5] kg; P = 0.007)
and body fat percentage (-1 [-2, 0]%; P = 0.044) and moderate improvements in C
reactive protein (-1.3 [-2.4, -0.2] mg.L(-1); P = 0.028) and exercise capacity
(95 [50, 139] m; P < 0.001). At follow-up, changes in body mass (-2.0 [-3.5,
0.5] kg; P = 0.010), body fat percentage (-1 [-2, 0]%; P = 0.033), and C-reactive
protein (-1.3 [-2.5, -0.1] mg.L(-1); P = 0.037) were maintained and exercise
capacity was further improved (132 [90, 175] m; P < 0.001). This trial is
registered with ClinicalTrials.gov NCT01546792.
PMID- 25136553
TI - Bone tissue engineering and regeneration.
PMID- 25136551
TI - The evolving role of radiosurgery in the management of radiation-induced
meningiomas: a review of current advances and future directions.
AB - Meningiomas are among the most common primary adult brain tumors, which arise
either spontaneously or secondary to environmental factors such as ionizing
radiation. The latter are referred to as radiation-induced meningiomas (RIMs)
which, while much less common than their spontaneous counterparts, are
challenging from a management point of view. Similar to spontaneous meningiomas,
the optimal management of RIMs is complete surgical resection. However, given
their high grade, multiplicity, tendency to invade bone and venous sinuses, and
high recurrence rate, this cannot always be accomplished safely. Therefore, other
therapeutic modalities, such as stereotactic radiosurgery, have emerged. In the
current review, we provide an overview of the historical outcomes achieved for
RIMs through radiosurgery and microsurgical resection. Furthermore, we provide a
discussion of clinical and radiological parameters that affect the decision
making process with regard to the management of RIMs. We also provide an outline
of recent changes in our understanding of RIMs, based on molecular and genetic
markers, and how these will change our management perspective. We conclude the
review by summarizing some of the current obstacles in the management of RIMs
with SRS and how current and future research can address these challenges.
PMID- 25136552
TI - Alga Ecklonia bicyclis, Tribulus terrestris, and glucosamine oligosaccharide
improve erectile function, sexual quality of life, and ejaculation function in
patients with moderate mild-moderate erectile dysfunction: a prospective,
randomized, placebo-controlled, single-blinded study.
AB - We aimed to evaluate the efficacy of oral therapy with alga Ecklonia bicyclis,
Tribulus terrestris, and glucosamine oligosaccharide (Tradamix TX1000) in
patients with erectile dysfunction (ED) at 3 months of follow-up. From January
2013 to September 2013, 177 patients diagnosed with mild-moderate ED (IIEF-EF <
26) were enrolled in this multicenter, single-blinded, placebo-controlled study
and randomized in Group A (Tradamix, n = 87) and Group B (placebo, n = 90).
Penile color Doppler ultrasound measures, IIEF-15 questionnaire, male sexual
health questionnaire-ejaculation disorder (MSHQ-EjD), and sexual quality of life
(SQoL-M) were collected. We observed significant changes of the IIEF-15 in Group
A (mean difference: 11.54; P < 0.05) at 3 months versus Group B (P < 0.05). PSV
(P < 0.05), IIEF-intercourse satisfaction (P < 0.05), IIEF-orgasmic function
(mean P < 0.05), IIEF-sexual desire (P < 0.05), IIEF-overall satisfaction (P <
0.05), MSHQ-EjD (mean difference: 1.21; P < 0.05), and SQoL-M (mean difference:
10.2; P < 0.05) were significantly changed in Group A versus baseline and Group
B. Patients with moderate arterial dysfunction showed significant increase of PSV
(P < 0.05), IIEF-EF (P < 0.05), MSHQ-EjD (P < 0.05), and SQoL-M (P < 0.05) in
Group A. Therapy with Tradamix improves erectile and ejaculation function and
sexual quality of life in patients with mild-moderate ED and in particular for
those with moderate arterial dysfunction.
PMID- 25136554
TI - The different dose-volume effects of normal tissue complication probability using
LASSO for acute small-bowel toxicity during radiotherapy in gynecological
patients with or without prior abdominal surgery.
AB - PURPOSE: To develop normal tissue complication probability (NTCP) model with
least absolute shrinkage and selection operator (LASSO) to analyze dose-volume
effects that influence the incidence of acute diarrhea among gynecological
patients with/without prior abdominal surgery. METHODS AND MATERIALS: Ninety-five
patients receiving gynecologic radiotherapy (RT) were enrolled. The endpoint was
defined as the grade 2(+) acute diarrhea toxicity during treatment. We obtained
the range of small-bowel volume in V4 Gy to V40 Gy of dose. RESULTS: The number
of patients experiencing grade 2(+) acute diarrhea toxicity was 23/61 (38%) in
the group without abdominal surgery (group 0) and 17/34 (50%) patients with
abdominal surgery (group 1). The most significant predictor was found for the
logistic NTCP model with V16 Gy as the cutoff dose for group 0 and V40 Gy for
group 1. Logistic regression NTCP model parameters were TV10 ~ 290 cc for V16 Gy
and TV10 ~ 75 cc for V40 Gy, respectively. CONCLUSION: To keep the incidence of
grade 2(+) acute small-bowel toxicity below 10%, we suggest that small-bowel
volume above the prescription dose (V16 Gy) should be held to <290 cc for
patients without abdominal surgery, and the prescription dose (V40 Gy) should be
maintained <75 cc for patients with abdominal surgery.
PMID- 25136556
TI - miRNA signature in mouse spermatogonial stem cells revealed by high-throughput
sequencing.
AB - Spermatogonial stem cells (SSCs) play fundamental roles in spermatogenesis.
Although a handful of genes have been discovered as key regulators of SSC self
renewal and differentiation, the regulatory network responsible for SSC function
remains unclear. In particular, small RNA signatures during mouse spermatogenesis
are not yet systematically investigated. Here, using next generation sequencing,
we compared small RNA signatures of in vitro expanded SSCs, testis-derived
somatic cells (Sertoli cells), developing germ cells, mouse embryonic stem cells
(ESCs), and mouse mesenchymal stem cells among mouse embryonic stem cells (ESCs)
to address small RNA transition during mouse spermatogenesis. The results
manifest that small RNA transition during mouse spermatogenesis displays overall
declined expression profiles of miRNAs and endo-siRNAs, in parallel with elevated
expression profiles of piRNAs, resulting in the normal biogenesis of sperms.
Meanwhile, several novel miRNAs were preferentially expressed in mouse SSCs, and
further investigation of their functional annotation will allow insights into the
mechanisms involved in the regulation of SSC activities. We also demonstrated the
similarity of miRNA signatures between SSCs and ESCs, thereby providing a new
clue to understanding the molecular basis underlying the easy conversion of SSCs
to ESCs.
PMID- 25136558
TI - Alteration of interictal brain activity in patients with temporal lobe epilepsy
in the left dominant hemisphere: a resting-state MEG study.
AB - Resting MEG activities were compared between patients with left temporal lobe
epilepsy (LTLE) and normal controls. Using SAMg2, the activities of MEG data were
reconstructed and normalized. Significantly elevated SAMg2 signals were found in
LTLE patients in the left temporal lobe and medial structures. Marked decreases
of SAMg2 signals were found in the wide extratemporal lobe regions, such as the
bilateral visual cortex. The study also demonstrated a positive correlation
between the seizure frequency and brain activities of the abnormal regions after
the multiple linear regression analysis. These results suggested that the
aberrant brain activities not only were related to the epileptogenic zones, but
also existed in other extratemporal regions in patients with LTLE. The activities
of the aberrant regions could be further damaged with the increase of the seizure
frequency. Our findings indicated that LTLE could be a multifocal disease,
including complex epileptic networks and brain dysfunction networks.
PMID- 25136555
TI - Modelling cochlear mechanics.
AB - The cochlea plays a crucial role in mammal hearing. The basic function of the
cochlea is to map sounds of different frequencies onto corresponding
characteristic positions on the basilar membrane (BM). Sounds enter the fluid
filled cochlea and cause deflection of the BM due to pressure differences between
the cochlear fluid chambers. These deflections travel along the cochlea,
increasing in amplitude, until a frequency-dependent characteristic position and
then decay away rapidly. The hair cells can detect these deflections and encode
them as neural signals. Modelling the mechanics of the cochlea is of help in
interpreting experimental observations and also can provide predictions of the
results of experiments that cannot currently be performed due to technical
limitations. This paper focuses on reviewing the numerical modelling of the
mechanical and electrical processes in the cochlea, which include fluid coupling,
micromechanics, the cochlear amplifier, nonlinearity, and electrical coupling.
PMID- 25136559
TI - Analysis of genotype 1b hepatitis C virus IRES in serum and peripheral blood
mononuclear cells in patients treated with interferon and ribavirin.
AB - Hepatitis C virus (HCV) highly conserved IRES (internal ribosome entry site)
sequence, localized within the 5(')-untranslated region (5(')UTR), may determine
viral properties like replication efficiency and cell tropism. The aim of the
present study was to characterize newly emerging 5(')UTR variants in serum and
peripheral blood mononuclear cells (PBMC) in chronic hepatitis C patients treated
with interferon (IFN) and ribavirin and to identify their effect on IRES
secondary structures. The study group consisted of 87 patients infected with
genotype 1b from whom serum and PBMC samples were collected at 9 time points
(before, during, and after treatment). New 5(')UTR variants developed in 9
patients. Out of the overall 14 new variants, 9 (64%) were found in PBMC. HCV
variants with decreased thermodynamic stability were identified only in PBMC and
C183U mutation was the most common one in this compartment. In conclusion,
antiviral treatment may favor emergence of new 5(')UTR variants both in blood and
in PBMC compartments. However, variants developing in the latter compartment were
predicted to have lower thermodynamic stability of the IRES secondary structures
compared to serum strains. C-U change in position 183, which has not been
described previously, might indicate viral adaptation to lymphoid cells.
PMID- 25136557
TI - Influence of electric, magnetic, and electromagnetic fields on the circadian
system: current stage of knowledge.
AB - One of the side effects of each electrical device work is the electromagnetic
field generated near its workplace. All organisms, including humans, are exposed
daily to the influence of different types of this field, characterized by various
physical parameters. Therefore, it is important to accurately determine the
effects of an electromagnetic field on the physiological and pathological
processes occurring in cells, tissues, and organs. Numerous epidemiological and
experimental data suggest that the extremely low frequency magnetic field
generated by electrical transmission lines and electrically powered devices and
the high frequencies electromagnetic radiation emitted by electronic devices have
a potentially negative impact on the circadian system. On the other hand, several
studies have found no influence of these fields on chronobiological parameters.
According to the current state of knowledge, some previously proposed hypotheses,
including one concerning the key role of melatonin secretion disruption in
pathogenesis of electromagnetic field induced diseases, need to be revised. This
paper reviews the data on the effect of electric, magnetic, and electromagnetic
fields on melatonin and cortisol rhythms-two major markers of the circadian
system as well as on sleep. It also provides the basic information about the
nature, classification, parameters, and sources of these fields.
PMID- 25136560
TI - Evaluation of the influence of formulation and process variables on mechanical
properties of oral mucoadhesive films using multivariate data analysis.
AB - Oral mucosa is an attractive region for the local and systemic application of
many drugs. Oral mucoadhesive films are preferred for their prolonged time of
residence, the improved bioavailability of the drug they contain, their painless
application, their protection against lesions, and their nonirritating
properties. This work was focused on preparation of nonmedicated carmellose-based
films using both solvent casting and impregnation methods, respectively.
Moreover, a modern approach to evaluation of mucoadhesive films applying analysis
of texture and subsequent multivariate data analysis was used. In this
experiment, puncture strength strongly correlated with tensile strength and could
be used to obtain necessary information about the mechanical film characteristics
in films prepared using both methods. Puncture work and tensile work were not
correlated in films prepared using the solvent casting method, as increasing the
amount of glycerol led to an increase in the puncture work in thinner films. All
measured texture parameters in films prepared by impregnation were significantly
smaller compared to films prepared by solvent casting. Moreover, a relationship
between the amount of glycerol and film thickness was observed, and a greater
recalculated tensile/puncture strength was needed for an increased thickness in
films prepared by impregnation.
PMID- 25136562
TI - Estimates of the number of people living with HIV in Italy.
AB - Objective. To estimate the HIV prevalence and the number of people living with
HIV (PLHIV) in Italy with a projection for 2020. Methods. Two methods elaborated
by Joint United Nations Programme on HIV/AIDS (UNAIDS) were used: Estimate and
Projection Package and Spectrum. Results. A total of 123,000 (115,000-145,000)
individuals aged 15 or more were estimated to be living with HIV in Italy at the
end of 2012 and the estimated HIV prevalence was 0.28 (0.24-0.32) per 100
residents aged 15 or more. In 2012, the estimated number of new HIV infections
among adults was 3,000 (2,700-4,000), and the number of adults in need for ART
was 93,000 (80,000-110,000). The projection estimates that 130,000 (110,000
150,000) adults will live with HIV/AIDS in 2020 in Italy. Conclusion. Estimates
of PLHIV in Italy stress the high number of PLHIV in need of care and treatment,
as well as the need for more information and prevention campaigns.
PMID- 25136561
TI - Structural insight into the DNA-binding mode of the primosomal proteins PriA,
PriB, and DnaT.
AB - Replication restart primosome is a complex dynamic system that is essential for
bacterial survival. This system uses various proteins to reinitiate chromosomal
DNA replication to maintain genetic integrity after DNA damage. The replication
restart primosome in Escherichia coli is composed of PriA helicase, PriB, PriC,
DnaT, DnaC, DnaB helicase, and DnaG primase. The assembly of the protein
complexes within the forked DNA responsible for reloading the replicative DnaB
helicase anywhere on the chromosome for genome duplication requires the
coordination of transient biomolecular interactions. Over the last decade,
investigations on the structure and mechanism of these nucleoproteins have
provided considerable insight into primosome assembly. In this review, we
summarize and discuss our current knowledge and recent advances on the DNA
binding mode of the primosomal proteins PriA, PriB, and DnaT.
PMID- 25136564
TI - Changes in biochemical characteristics and activities of ripening associated
enzymes in mango fruit during the storage at different temperatures.
AB - As a part of the study to explore the possible strategy for enhancing the shelf
life of mango fruits, we investigated the changes in biochemical parameters and
activities of ripening associated enzymes of Ashwina hybrid mangoes at 4-day
regular intervals during storage at -10 degrees C, 4 degrees C, and 30 +/- 1
degrees C. Titratable acidity, vitamin C, starch content, and reducing sugar were
higher at unripe state and gradually decreased with the increasing of storage
time at all storage temperatures while phenol content, total soluble solid, total
sugar, and nonreducing sugar contents gradually increased. The activities of
amylase, alpha-mannosidase, alpha-glucosidase, and invertase increased sharply
within first few days and decreased significantly in the later stage of ripening
at 30 +/- 1 degrees C. Meanwhile polyphenol oxidase, beta-galactosidase, and beta
hexosaminidase predominantly increased significantly with the increasing days of
storage till later stage of ripening. At -10 degrees C and 4 degrees C, the
enzymes as well as carbohydrate contents of storage mango changed slightly up to
4 days and thereafter the enzyme became fully dormant. The results indicated that
increase in storage temperature and time correlated with changes in biochemical
parameters and activities of glycosidases suggested the suppression of beta
galactosidase and beta-hexosaminidase might enhance the shelf life of mango
fruits.
PMID- 25136563
TI - Effects of parity and serum prolactin levels on the incidence and regression of
DMBA-induced tumors in OFA hr/hr rats.
AB - Prolactin (PRL) is a key player in the development of mammary cancer. We studied
the effects of parity or hyperprolactinemia on mammary carcinogenesis in OFA
hr/hr treated with 7,12-dimethylbenzanthracene. They were divided into three
groups: nulliparous (Null), primiparous (PL, after pregnancy and lactation), and
hyperprolactinemic rats (I, implanted in the arcuate nucleus with 17beta
estradiol). The tumor incidence was similar in the three groups. However, a
higher percentage of regressing tumors was evident in the PL group. Serum PRL,
mammary development, and mammary beta-casein content were higher in I rats
compared to Null. The expression of hormone receptors was similar in the
different groups. However, mammary tissue from PL rats bearing tumors had
increased expression of PRL and estrogen alpha receptors compared to rats free of
tumors. Our results suggest that serum PRL levels do not have relevance on the
incidence of tumors, probably because the low levels of PRL in OFA rats are not
further decreased by PL like in other strains. However, supraphysiological levels
of PRL affect carcinogenesis. PL induces regression of the tumors due to the
differentiation produced on the mammary cells. Alterations in the expression of
hormonal receptors may be involved in progression and regression of tumors.
PMID- 25136565
TI - Recent advances in polyamine metabolism and abiotic stress tolerance.
AB - Global warming is an alarming problem in agriculture and its effect on yield loss
has been estimated to be five per cent for every degree centigrade rise in
temperature. Plants exhibit multiple mechanisms like optimizing signaling
pathway, involvement of secondary messengers, production of biomolecules
specifically in response to stress, modulation of various metabolic networks in
accordance with stress, and so forth, in order to overcome abiotic stress
factors. Many structural genes and networks of pathway were identified and
reported in plant systems for abiotic stress tolerance. One such crucial
metabolic pathway that is involved in normal physiological function and also gets
modulated during stress to impart tolerance is polyamine metabolic pathway.
Besides the role of structural genes, it is also important to know the mechanism
by which these structural genes are regulated during stress. Present review
highlights polyamine biosynthesis, catabolism, and its role in abiotic stress
tolerance with special reference to plant systems. Additionally, a system based
approach is discussed as a potential strategy to dissect the existing variation
in crop species in unraveling the interacting regulatory components/genetic
determinants related to PAs mediated abiotic stress tolerance.
PMID- 25136567
TI - Cell death in human health and disease.
PMID- 25136566
TI - Protective effect of ethanolic extract of Tabernaemontana divaricata (L.) R. Br.
against DEN and Fe NTA induced liver necrosis in Wistar Albino rats.
AB - This study is an attempt to evaluate the hepatoprotective activity of
Tabernaemontana divaricata against DEN and Fe NTA induced liver necrosis in rats.
Ethanolic extract of the whole plant of Tabernaemontana divaricata at doses of
200 and 400 mg/kg body weight and 5-fluorouracil (standard drug) was orally
administered to male Wistar Albino rats once daily for 24 weeks, simultaneously
treated with the carcinogen DEN and Fe NTA. In simultaneously treated animals,
the plant extract significantly decreased the levels of uric acid, bilirubin,
AST, ALT, and ALP in serum and increased the levels of liver marker enzymes in
liver. Treatment with the extracts resulted in a significant increase in the
levels of antioxidants accompanied by a marked reduction in the levels of
malondialdehyde when compared to DEN and Fe NTA treated group. When compared with
200 mg/kg bw rats, 400 mg/kg bw rats and 5-fluorouracil treated rats showed
better results in all the parameters. The histopathological studies confirmed the
protective effects of extract against DEN and Fe NTA induced liver necrosis.
Thus, it could be concluded that the use of Tabernaemontana divaricata extract in
the treatment of carcinogen induced hepatic necrosis.
PMID- 25136569
TI - Effects of parathyroid hormone on calcium ions in rat bone marrow mesenchymal
stem cells.
AB - The present study was conducted in order to explore the mechanisms whereby
parathyroid hormone (PTH) maintains in vitro proliferation of bone marrow
mesenchymal stem cells (BMSCs). Bone marrow was isolated from Sprague Dawley (SD)
rat femurs, cultured in vitro, and passaged using a cell adherent culture method.
The BMSC proliferation was evaluated by the methyl thiazolyl tetrazolium (MTT)
assay and the fluorescence intensity of calcium ions in BMSCs was analyzed by
laser scanning confocal microscopy (LSCM). Our results show that BMSC
proliferation in the experimental group treated with PTH was more significant
than controls. The calcium ion fluorescence intensity in BMSCs was significantly
higher for the experimental group as compared to the control group. For each
group, there was significant difference in the fluorescence intensity of calcium
ions in BMSCs between 7 d and 14 d. In conclusion, parathyroid hormone increased
the fluorescence intensity of calcium ions in BMSCs, which might represent a key
mechanism whereby BMSC proliferation is maintained.
PMID- 25136568
TI - Clinical applications of platelet-rich plasma in patellar tendinopathy.
AB - Platelet-rich plasma (PRP), a blood derivative with high concentrations of
platelets, has been found to have high levels of autologous growth factors (GFs),
such as transforming growth factor-beta (TGF-beta), platelet-derived growth
factor (PDGF), fibroblastic growth factor (FGF), vascular endothelial growth
factor (VEGF), and epidermal growth factor (EGF). These GFs and other biological
active proteins of PRP can promote tissue healing through the regulation of
fibrosis and angiogenesis. Moreover, PRP is considered to be safe due to its
autologous nature and long-term usage without any reported major complications.
Therefore, PRP therapy could be an option in treating overused tendon damage such
as chronic tendinopathy. Here, we present a systematic review highlighting the
clinical effectiveness of PRP injection therapy in patellar tendinopathy, which
is a major cause of athletes to retire from their respective careers.
PMID- 25136570
TI - Effects of crude extracts from medicinal herbs Rhazya stricta and Zingiber
officinale on growth and proliferation of human brain cancer cell line in vitro.
AB - Hitherto, limited clinical impact has been achieved in the treatment of
glioblastoma (GBMs). Although phytochemicals found in medicinal herbs can provide
mankind with new therapeutic remedies, single agent intervention has failed to
bring the expected outcome in clinical trials. Therefore, combinations of several
agents at once are gaining increasing attractiveness. In the present study, we
investigated the effects of crude alkaloid (CAERS) and flavonoid (CFEZO) extracts
prepared from medicinal herbs, Rhazya stricta and Zingiber officinale,
respectively, on the growth of human GBM cell line, U251. R. stricta and Z.
officinale are traditionally used in folkloric medicine and have antioxidant,
anticarcinogenic, and free radical scavenging properties. Combination of CAERS
and CFEZO treatments synergistically suppressed proliferation and colony
formation and effectively induced morphological and biochemical features of
apoptosis in U251 cells. Apoptosis induction was mediated by release of
mitochondrial cytochrome c, increased Bax : Bcl-2 ratio, enhanced activities of
caspase-3 and -9, and PARP-1 cleavage. CAERS and CFEZO treatments decreased
expression levels of nuclear NF-kappaBp65, survivin, XIAP, and cyclin D1 and
increased expression level of p53, p21, and Noxa. These results suggest that
combination of CAERS and CFEZO provides a useful foundation for studying and
developing novel chemotherapeutic agents for the treatment of GBM.
PMID- 25136571
TI - Recognition of 27-class protein folds by adding the interaction of segments and
motif information.
AB - The recognition of protein folds is an important step for the prediction of
protein structure and function. After the recognition of 27-class protein folds
in 2001 by Ding and Dubchak, prediction algorithms, prediction parameters, and
new datasets for the prediction of protein folds have been improved. However, the
influences of interactions from predicted secondary structure segments and motif
information on protein folding have not been considered. Therefore, the
recognition of 27-class protein folds with the interaction of segments and motif
information is very important. Based on the 27-class folds dataset built by Liu
et al., amino acid composition, the interactions of secondary structure segments,
motif frequency, and predicted secondary structure information were extracted.
Using the Random Forest algorithm and the ensemble classification strategy, 27
class protein folds and corresponding structural classification were identified
by independent test. The overall accuracy of the testing set and structural
classification measured up to 78.38% and 92.55%, respectively. When the training
set and testing set were combined, the overall accuracy by 5-fold cross
validation was 81.16%. In order to compare with the results of previous
researchers, the method above was tested on Ding and Dubchak's dataset which has
been widely used by many previous researchers, and an improved overall accuracy
70.24% was obtained.
PMID- 25136572
TI - High potential source for biomass degradation enzyme discovery and environmental
aspects revealed through metagenomics of Indian buffalo rumen.
AB - The complex microbiomes of the rumen functions as an effective system for plant
cell wall degradation, and biomass utilization provide genetic resource for
degrading microbial enzymes that could be used in the production of biofuel.
Therefore the buffalo rumen microbiota was surveyed using shot gun sequencing.
This metagenomic sequencing generated 3.9 GB of sequences and data were assembled
into 137270 contiguous sequences (contigs). We identified potential 2614 contigs
encoding biomass degrading enzymes including glycoside hydrolases (GH: 1943
contigs), carbohydrate binding module (CBM: 23 contigs), glycosyl transferase
(GT: 373 contigs), carbohydrate esterases (CE: 259 contigs), and polysaccharide
lyases (PE: 16 contigs). The hierarchical clustering of buffalo metagenomes
demonstrated the similarities and dissimilarity in microbial community structures
and functional capacity. This demonstrates that buffalo rumen microbiome was
considerably enriched in functional genes involved in polysaccharide degradation
with great prospects to obtain new molecules that may be applied in the biofuel
industry.
PMID- 25136573
TI - Designing peptide-based HIV vaccine for Chinese.
AB - CD4+ T cells are central to the induction and maintenance of CD8+ T cell and
antibody-producing B cell responses, and the latter are essential for the
protection against disease in subjects with HIV infection. How to elicit HIV
specific CD4+ T cell responses in a given population using vaccines is one of the
major areas of current HIV vaccine research. To design vaccine that targets
specifically Chinese, we assembled a database that is comprised of sequences from
821 Chinese HIV isolates and 46 human leukocyte antigen (HLA) DR alleles
identified in Chinese population. We then predicted 20 potential HIV epitopes
using bioinformatics approaches. The combination of these 20 epitopes has a
theoretical coverage of 98.1% of the population for both the prevalent HIV
genotypes and also Chinese HLA-DR types. We suggest that testing this vaccine
experimentally will facilitate the development of a CD4+ T cell vaccine
especially catered for Chinese.
PMID- 25136574
TI - Monte Carlo simulation of protein adsorption on energetically heterogeneous
surfaces.
AB - The modified triangular-well potential model was applied to incorporate the
effect of surface energy on the adsorption of particles or proteins on
energetically heterogeneous surfaces. The method is convenient in simulating the
adsorption on heterogeneous surface of which different region possesses different
free energy. Spherical particles with attractive forces were added on the surface
and underwent surface diffusion before they were quenched in place. It was seen
that the ratio of surface energies of two regions had to be greater than 10 in
order to simulate the adsorption in which the particles were selectively adsorbed
on a favorable area. At a fixed ratio of surface energies, the obtained
structures were similar. If the ratio was less than 10, the probability of
adsorption on any site on the surface was not much different so the adsorption
would be homogeneous adsorption. The method, thus, could be applied widely to
simulate the adsorption of various conditions.
PMID- 25136577
TI - Gender and family disparities in suicide attempt and role of socioeconomic,
school, and health-related difficulties in early adolescence.
AB - Suicide attempt (SA) is common in early adolescence and the risk may differ
between boys and girls in nonintact families partly because of socioeconomic,
school, and health-related difficulties. This study explored the gender and
family disparities and the role of these covariates. Questionnaires were
completed by 1,559 middle-school adolescents from north-eastern France including
sex, age, socioeconomic factors (family structure, nationality, parents'
education, father's occupation, family income, and social support), grade
repetition, depressive symptoms, sustained violence, sexual abuse, unhealthy
behaviors (tobacco/alcohol/cannabis/hard drug use), SA, and their first
occurrence over adolescent's life course. Data were analyzed using Cox regression
models. SA affected 12.5% of girls and 7.2% of boys (P < 0.001). The girls living
with parents divorced/separated, in reconstructed families, and with single
parents had a 3-fold higher SA risk than those living in intact families. Over
63% of the risk was explained by socioeconomic, school, and health-related
difficulties. No family disparities were observed among boys. Girls had a 1.74
time higher SA risk than boys, and 45% of the risk was explained by
socioeconomic, school, and mental difficulties and violence. SA prevention should
be performed in early adolescence and consider gender and family differences and
the role of socioeconomic, school, and health-related difficulties.
PMID- 25136576
TI - Novel hypoxanthine guanine phosphoribosyltransferase gene mutations in Saudi
Arabian hyperuricemia patients.
AB - Over the past decade, a steady increase in the incidence of HPRT-related
hyperuricemia (HRH) has been observed in Saudi Arabia. We examined all the nine
exons of HPRT gene for mutations in ten biochemically confirmed hyperuricemia
patients, including one female and three normal controls. In all, we identified
13 novel mutations in Saudi Arabian HPRT-related hyperuricemia patients
manifesting different levels of uric acid. The Lys103Met alteration was highly
recurrent and was observed in 50% of the cases, while Ala160Thr and Lys158Asn
substitutions were found in two patients. Moreover, in 70% of the patients >=2
mutations were detected concurrently in the HPRT gene. Interestingly, one of the
patients that harbored Lys103Met substitution along with two frameshift mutations
at codons 85 and 160 resulting in shortened protein demonstrated unusually high
serum uric acid level of 738 MUmol/L. Two of the seven point mutations that
resulted in amino acid change (Lys103Met and Val160Gly) were predicted to be
damaging by SIFT and Polyphen and were further analyzed for their protein
stability and function by molecular dynamics simulation. The identified novel
mutations in the HPRT gene may prove useful in the prenatal diagnosis and genetic
counseling.
PMID- 25136575
TI - Vagus nerve through alpha7 nAChR modulates lung infection and inflammation:
models, cells, and signals.
AB - Cholinergic anti-inflammatory pathway (CAP) bridges immune and nervous systems
and plays pleiotropic roles in modulating inflammation in animal models by
targeting different immune, proinflammatory, epithelial, endothelial, stem, and
progenitor cells and signaling pathways. Acute lung injury (ALI) is a devastating
inflammatory disease. It is pathogenically heterogeneous and involves many cells
and signaling pathways. Here, we emphasized the research regarding the modulatory
effects of CAP on animal models, cell population, and signaling pathways that
involved in the pathogenesis of ALI. By comparing the differential effects of CAP
on systemic and pulmonary inflammation, we postulated that a pulmonary
parasympathetic inflammatory reflex is formed to sense and respond to pathogens
in the lung. Work targeting the formation and function of pulmonary
parasympathetic inflammatory reflex would extend our understanding of how vagus
nerve senses, recognizes, and fights with pathogens and inflammatory responses.
PMID- 25136578
TI - Potassium channel ether a go-go1 is aberrantly expressed in human liposarcoma and
promotes tumorigenesis.
AB - The ether a go-go1 (Eag1) channel is overexpressed in a variety of cancers.
However, the expression and function of Eag1 in liposarcoma are poorly
understood. In the present study, the mRNA expression of Eag1 in different
adipose tissue samples was examined by real-time PCR. Then, the protein
expression of Eag1 in 131 different adipose tissues from 109 patients was
detected by immunohistochemistry. Next, the associations between Eag1 expression
and clinicopathological features of liposarcoma were analyzed. In addition, the
effects of Eag1 on liposarcoma cell proliferation and cycle were evaluated by CCK
8, colony formation, xenograft mouse model, and flow cytometry, respectively.
Finally, the activation of p38 mitogen-activated protein kinase (MAPK) was
detected by Western blot analysis to explain the detailed mechanisms of oncogenic
potential of Eag1 in liposarcoma. It was found that Eag1 was aberrantly expressed
in over 67% liposarcomas, with a higher frequency than in lipoma, hyperplasia,
inflammation, and normal adipose tissues. However, Eag1 expression was not
correlated with clinicopathological features of liposarcoma. Eag1 inhibitor
imipramine or Eag1-shRNA significantly suppressed the proliferation of
liposarcoma cells in vitro and in vivo, accompanying with accumulation of cells
in the G1 phase. These results suggest that Eag1 plays an important role in
regulating the proliferation and cell cycle of liposarcoma cells and might be a
potential therapeutic target for liposarcoma.
PMID- 25136579
TI - Management of poor responders in IVF: is there anything new?
AB - Despite the fact that in the last two decades an enormous number of papers on the
topic of poor ovarian response have been published in the literature, so far it
has been impossible to identify any efficient treatment to improve the ovarian
response and the clinical outcome of this group of patients. The incidence of
poor ovarian responders among infertile women has been estimated at 9-24% but
according to recent reviews, it seems to have slightly increased. The limitation
in quantifying the incidence of these patients among the infertile population is
due to the difficulty of a clear definition in literature. A recent paper by the
Bologna ESHRE working group on poor ovarian response has been the first real
attempt to find a common definition. Current literature proposes new risk factors
which could be the cause of a reduction in ovarian reserve, which also includes
genetic factors. This represents the first necessary step towards finding
applicable solutions for these patients. To date, there is a substantial lack of
literature that identifies an ideal protocol for these patients. The use of the
"Bologna criteria" and the introduction of long acting gonadotropin in clinical
practice have given rise to new promising stimulation protocols for this group of
patients.
PMID- 25136581
TI - High molecular weight proteins of Trypanosoma cruzi reduce cross-reaction with
Leishmania spp. in serological diagnosis tests.
AB - Chagas disease is caused by the parasite Trypanosoma cruzi. Because of its
distribution throughout Latin America, sometimes it can overlap with other
parasitic diseases, such as leishmaniasis, caused by Leishmania spp. This might
represent a problem when performing serological diagnosis, because both parasites
share antigens, resulting in cross-reactions. In the present work we evaluated
Mexican sera samples: 83.8% of chagasic patients recognized at least one antigen
of high molecular weight (>95 kDa) when evaluated by Western blot. Proteins of
130 kDa and 160 kDa are predominantly being recognized by asymptomatic chagasic
patients. When the proteins were extracted using Triton X-100 detergent, a larger
number of specific T. cruzi proteins were obtained. This protein fraction can be
used to increase specificity to 100% in Western blot assays without losing
sensitivity of the test. High molecular weight proteins of T. cruzi include
glycoproteins with a great amount of alphaMan (alpha-mannose), alphaGlc (alpha
glucose), GlcNAc (N-acetylglucosamine), and alphaGal (alpha-galactose) content
and these structures play an essential role in antigens recognition by antibodies
present in patients' sera.
PMID- 25136580
TI - The study of fetal rat model of intra-amniotic isoproterenol injection induced
heart dysfunction and phenotypic switch of contractile proteins.
AB - To establish a reliable isoproterenol induced heart dysfunction fetal rat model
and understand the switches of contractile proteins, 45 pregnant rats were
divided into 15 mg/kg-once, 15 mg/kg-twice, sham-operated once, sham-operated
twice, and control groups. And 18 adult rats were divided into isoproterenol
treated and control groups. H&E staining, Masson staining, and transmission
electron microscope were performed. Apoptotic rate assessed by TUNEL analysis and
expressions of ANP, BNP, MMP-2, and CTGF of hearts were measured. Intra-amniotic
injections of isoproterenol were supplied on E14.5 and E15.5 for fetuses and 7
day continuous intraperitoneal injections were performed for adults. Then
echocardiography was performed with M-mode view assessment on E18.5 and 6 weeks
later, respectively. Isoproterenol twice treated fetuses exhibited significant
changes in histological evaluation, and mitochondrial damages were significantly
severe with increased apoptotic rate. ANP and BNP increased and that of MMP-2
increased in isoproterenol twice treated group compared to control group, without
CTGF. The isoforms transition of troponin I and myosin heavy chain of fetal heart
dysfunction were opposite to adult procedure. The administration of intra
amniotic isoproterenol to fetal rats could induce heart dysfunction and the
regulation of contractile proteins of fetuses was different from adult procedure.
PMID- 25136582
TI - Proton-based stereotactic ablative radiotherapy in early-stage non-small-cell
lung cancer.
AB - Stereotactic ablative radiotherapy (SABR), a recent implementation in the
practice of radiation oncology, has been shown to confer high rates of local
control in the treatment of early stage non-small-cell lung cancer (NSCLC). This
technique, which involves limited invasive procedures and reduced treatment
intervals, offers definitive treatment for patients unable or unwilling to
undergo an operation. The use of protons in SABR delivery confers the added
physical advantage of normal tissue sparing due to the absence of collateral
radiation dose delivered to regions distal to the target. This may translate into
clinical benefit and a decreased risk of clinical toxicity in patients with
nearby critical structures or limited pulmonary reserve. In this review, we
present the rationale for proton-based SABR, principles relating to the delivery
and planning of this modality, and a summary of published clinical studies.
PMID- 25136583
TI - Rho GTPase-activating protein 35 rs1052667 polymorphism and osteosarcoma risk and
prognosis.
AB - The Rho GTPase-activating protein 35 (ARHGAP35), an important Rho family GTPase
activating protein, may be associated with tumorigenesis of some tumors. Here, we
investigated the relationship between an important polymorphic variant at 3'-UTR
of this gene (rs1052667) and osteosarcoma risk and prognosis. This hospital-based
case-control study, including 247 osteosarcoma patients and 428 age-, sex-, and
race-matched healthy controls, was conducted in Guangxi population. Genotypes
were tested using TaqMan PCR technique. We found a significant difference in the
frequency of rs1052667 genotypes between cases and controls. Compared with the
homozygote of rs1052667 C alleles (rs1052667-CC), the genotypes with rs1052667 T
alleles (namely, rs1052667-CT or -TT) increased osteosarcoma risk (odds ratios:
2.41 and 7.35, resp.). Moreover, rs1052667 polymorphism was correlated with such
pathological features of osteosarcoma as tumor size, tumor grade, and tumor
metastasis. Additionally, this polymorphism also modified the overall survival
and recurrence-free survival of osteosarcoma cases. Like tumor grade, ARHGAP35
rs1052667 polymorphism was an independent prognostic factor influencing the
survival of osteosarcoma. These results suggest that ARHGAP35 rs1052667
polymorphism may be associated with osteosarcoma risk and prognosis.
PMID- 25136584
TI - Effect of exercise intensity on isoform-specific expressions of NT-PGC-1 alpha
mRNA in mouse skeletal muscle.
AB - PGC-1alpha is an inducible transcriptional coactivator that regulates
mitochondrial biogenesis and cellular energy metabolism in skeletal muscle.
Recent studies have identified two additional PGC-1alpha transcripts that are
derived from an alternative exon 1 (exon 1b) and induced by exercise. Given that
the PGC-1alpha gene also produces NT-PGC-1alpha transcript by alternative 3(')
splicing between exon 6 and exon 7, we have investigated isoform-specific
expression of NT-PGC-1alpha mRNA in mouse skeletal muscle during physical
exercise with different intensities. We report here that NT-PGC-1alpha-a mRNA
expression derived from a canonical exon 1 (exon 1a) is increased by high
intensity exercise and AMPK activator AICAR in mouse skeletal muscle but not
altered by low- and medium-intensity exercise and beta 2-adrenergic receptor
agonist clenbuterol. In contrast, the alternative exon 1b-driven NT-PGC-1alpha-b
(PGC-1alpha4) and NT-PGC-1alpha-c are highly induced by low-, medium-, and high
intensity exercise, AICAR, and clenbuterol. Ectopic expression of NT-PGC-1alpha-a
in C2C12 myotube cells upregulates myosin heavy chain (MHC I, MHC II a) and
Glut4, which represent oxidative fibers, and promotes the expression of
mitochondrial genes (Cyc1, COX5B, and ATP5B). In line with gene expression data,
citrate synthase activity was significantly increased by NT-PGC-1alpha-a in C2C12
myotube cells. Our results indicate the regulatory role for NT-PGC-1alpha-a in
mitochondrial biogenesis and adaptation of skeletal muscle to endurance exercise.
PMID- 25136586
TI - New drugs on the Internet: the case of Camfetamine.
AB - INTRODUCTION: The number of new psychoactive substances (NPS) advertised for sale
online is constantly increasing and it has become a phenomenon of global concern.
Among NPS, Camfetamine has been rediscovered as recreational drug in 2011. Very
little information is still available in the scientific literature on its nature
and potential health risks. METHODS: Data in scientific literature were
integrated with a multilingual qualitative assessment of a range of online
resources over the period of 32 months (May 2011-January 2014). RESULTS: N-Methyl
3-phenyl-norbornan-2-amine (Camfetamine) may act as an indirect dopaminergic
agonist in the central nervous system and may have mild-moderate opioid activity
too. There are no current epidemiological data about recreational use of
Camfetamine; our research shows that it is indeed used especially by individuals
with a history of recreational polydrug misuse. It facilitates mental alertness,
induces relaxation, and, unlike many other stimulants, seems not to be associated
with severe physical effects. Valid causes for concern issued in our research may
be Camfetamine intravenous or intramuscular administration as well as its use in
conjunction with other psychoactive substances. CONCLUSIONS: It is here
highlighted that more large-scale studies need to be carried out to confirm and
better describe both the extent of Camfetamine misuse and possible
psychotropic/adverse effects.
PMID- 25136587
TI - Diversity and enzymatic profiling of halotolerant micromycetes from Sebkha El
Melah, a Saharan salt flat in southern Tunisia.
AB - Twenty-one moderately halotolerant fungi have been isolated from sample ashes
collected from Sebkha El Melah, a Saharan salt flat located in southern Tunisia.
Based on morphology and sequence inference from the internal transcribed spacer
regions, 28S rRNA gene and other specific genes such as beta-tubulin, actin,
calmodulin, and glyceraldehyde-3-phosphate dehydrogenase, the isolates were found
to be distributed over 15 taxa belonging to 6 genera of Ascomycetes: Cladosporium
(n = 3), Alternaria (n = 4), Aspergillus (n = 3), Penicillium (n = 5), Ulocladium
(n = 2), and Engyodontium (n = 2). Their tolerance to different concentrations of
salt in solid and liquid media was examined. Excepting Cladosporium
cladosporioides JA18, all isolates were considered as alkali-halotolerant since
they were able to grow in media containing 10% of salt with an initial pH 10. All
isolates were resistant to oxidative stresses and low temperature whereas 5
strains belonging to Alternaria, Ulocladium, and Aspergillus genera were able to
grow at 45 degrees C. The screening of fungal strains for sets of enzyme
production, namely, cellulase (CMCase), amylase, protease, lipase, and laccase,
in presence of 10% NaCl, showed a variety of extracellular hydrolytic and
oxidative profiles. Protease was the most abundant enzyme produced whereas
laccase producers were members of the genus Cladosporium.
PMID- 25136585
TI - Roles of inflammation, oxidative stress, and vascular dysfunction in
hypertension.
AB - Hypertension is a complex condition and is the most common cardiovascular risk
factor, contributing to widespread morbidity and mortality. Approximately 90% of
hypertension cases are classified as essential hypertension, where the precise
cause is unknown. Hypertension is associated with inflammation; however, whether
inflammation is a cause or effect of hypertension is not well understood. The
purpose of this review is to describe evidence from human and animal studies that
inflammation leads to the development of hypertension, as well as the evidence
for involvement of oxidative stress and endothelial dysfunction--both thought to
be key steps in the development of hypertension. Other potential proinflammatory
conditions that contribute to hypertension-such as activation of the sympathetic
nervous system, aging, and elevated aldosterone--are also discussed. Finally, we
consider the potential benefit of anti-inflammatory drugs and statins for
antihypertensive therapy. The evidence reviewed suggests that inflammation can
lead to the development of hypertension and that oxidative stress and endothelial
dysfunction are involved in the inflammatory cascade. Aging and aldosterone may
also both be involved in inflammation and hypertension. Hence, in the absence of
serious side effects, anti-inflammatory drugs could potentially be used to treat
hypertension in the future.
PMID- 25136588
TI - Expression and clinical significance of the autophagy proteins BECLIN 1 and LC3
in ovarian cancer.
AB - Autophagy is dysregulated in cancer and might be involved in ovarian
carcinogenesis. BECLIN-1, a protein that interacts with either BCL-2 or PI3k
class III, plays a critical role in the regulation of both autophagy and cell
death. Induction of autophagy is associated with the presence of vacuoles
characteristically labelled with the protein LC3. We have studied the biological
and clinical significance of BECLIN 1 and LC3 in ovary tumours of different
histological types. The positive expression of BECLIN 1 was well correlated with
the presence of LC3-positive autophagic vacuoles and was inversely correlated
with the expression of BCL-2. The latter inhibits the autophagy function of
BECLIN 1. We found that type I tumours, which are less aggressive than type II,
were more frequently expressing high level of BECLIN 1. Of note, tumours of
histologic grade III expressed low level of BECLIN 1. Consistently, high level of
expression of BECLIN 1 and LC3 in tumours is well correlated with the overall
survival of the patients. The present data are compatible with the hypotheses
that a low level of autophagy favours cancer progression and that ovary cancer
with upregulated autophagy has a less aggressive behaviour and is more responsive
to chemotherapy.
PMID- 25136589
TI - Event-specific risk factors predicting episodes of unprotected anal intercourse
with male nonregular partners among men who have sex with men using case
crossover study design.
AB - This study investigated event-specific factors that determine episodes of
unprotected and protected anal intercourse (UAI and PAI) among 215 men who have
sex with men (MSM), who used condoms inconsistently with nonregular partners
(NRP) in the last six months, in Hong Kong. A case-crossover study design was
used. Lower likelihood of episodes involving UAI with NRP was associated with (1)
five partner attributes (NRP were <35 years old, at least three previous anal sex
experiences with the NRP, perception that participant and the NRP had
asymmetrical sexual experience, perception that the NRP was feminine, and liking
toward the NRP; OR = 0.16-0.52), (2) six situational variables (the participant
having had UAI with another man in the last week, having discussed condom use,
perception that the NRP liked to use condom, partner's suggestion to have PAI,
participant's suggestion to have PAI, and participant's plan to use condoms; OR =
0.11-0.39), and (3) four environmental/setting variables (condoms already placed
at the venue, display of condom use promotion materials, participant's possession
of a condom, and the NRP possessed a condom; OR = 0.27-0.45). HIV prevention
targeting MSM should focus on event-specific protective factors, which may be
different from those obtained from studies distinguishing condom users versus
nonusers.
PMID- 25136590
TI - Methylamine-sensitive amperometric biosensor based on (His)6-tagged Hansenula
polymorpha methylamine oxidase immobilized on the gold nanoparticles.
AB - A novel methylamine-selective amperometric bienzyme biosensor based on
recombinant primary amine oxidase isolated from the recombinant yeast strain
Saccharomyces cerevisiae and commercial horseradish peroxidase is described. Two
amine oxidase preparations were used: free enzyme (AMO) and covalently
immobilized on the surface of gold nanoparticles (AMO-nAu). Some bioanalytical
parameters (sensitivity, selectivity, and storage stability) of the developed
biosensors were investigated. The sensitivity for both sensors is high: 1450 +/-
113 and 700 +/- 30 A(-1) .M(-1) .m(-2) for AMO-nAu biosensor, respectively. The
biosensors exhibit the linear range from 15 MUM to 150 MUM (AMO-nAu) and from 15
MUM to 60 MUM (AMO). The developed biosensor demonstrated a good selectivity
toward methylamine (MA) (signal for dimethylamine and trimethylamine is less than
5% and for ethylamine 15% compared to MA output) and reveals a satisfactory
storage stability. The constructed amperometric biosensor was used for MA assay
in real samples of fish products in comparison with chemical method. The values
obtained with both approaches different methods demonstrated a high correlation.
PMID- 25136591
TI - The effect of Babesia divergens infection on the spleen of Mongolian gerbils.
AB - Babesiosis is caused by intraerythrocytic protozoan parasites transmitted by
ticks and affects a wide range of domestic and wild animals and occasionally
humans. The current study aimed to investigate the effect of B. divergens
infected erythrocytes on spleen histopathology, cell cycle alteration, and the
presence of oxidative stress. Mongolian gerbils were challenged with 5 * 10(6)
Babesia divergens infected erythrocytes. Parasitemia reached approximately 77% at
day 5 postinfection. Infection also induced injury of the spleen. This was
evidenced with (i) increases in cellular damage of the spleen, (ii) decrease in
antioxidant capacity as indicated by decreased glutathione, catalase, and
superoxide dismutase levels, (iii) increased production of malondialdehyde and
nitric oxide derived products (nitrite/nitrate), and (iv) increased lactic acid
dehydrogenase activity and protein carbonyl content in the spleen. Infection
interfered with normal cell cycle of the spleen cells at G0/G1, S, and G2/M
phases. On the basis of the above results it can be hypothesized that B.
divergens infected erythrocytes could alter the spleen histopathology and cause
cell cycle alteration and induce oxidative stress in splenic tissue.
PMID- 25136592
TI - Automated synthesis of 18F-fluoropropoxytryptophan for amino acid transporter
system imaging.
AB - OBJECTIVE: This study was to develop a cGMP grade of
[(18)F]fluoropropoxytryptophan ((18)F-FTP) to assess tryptophan transporters
using an automated synthesizer. METHODS: Tosylpropoxytryptophan (Ts-TP) was
reacted with K(18)F/kryptofix complex. After column purification, solvent
evaporation, and hydrolysis, the identity and purity of the product were
validated by radio-TLC (1M-ammonium acetate : methanol = 4 : 1) and HPLC (C-18
column, methanol : water = 7 : 3) analyses. In vitro cellular uptake of (18)F-FTP
and (18)F-FDG was performed in human prostate cancer cells. PET imaging studies
were performed with (18)F-FTP and (18)F-FDG in prostate and small cell lung tumor
bearing mice (3.7 MBq/mouse, iv). RESULTS: Radio-TLC and HPLC analyses of (18)F
FTP showed that the Rf and Rt values were 0.9 and 9 min, respectively.
Radiochemical purity was >99%. The radiochemical yield was 37.7% (EOS 90 min,
decay corrected). Cellular uptake of (18)F-FTP and (18)F-FDG showed enhanced
uptake as a function of incubation time. PET imaging studies showed that (18)F
FTP had less tumor uptake than (18)F-FDG in prostate cancer model. However, (18)F
FTP had more uptake than (18)F-FDG in small cell lung cancer model. CONCLUSION:
(18)F-FTP could be synthesized with high radiochemical yield. Assessment of
upregulated transporters activity by (18)F-FTP may provide potential applications
in differential diagnosis and prediction of early treatment response.
PMID- 25136594
TI - Genetic testing in hereditary breast and ovarian cancer using massive parallel
sequencing.
AB - High throughput methods such as next generation sequencing are increasingly used
in molecular diagnosis. The aim of this study was to develop a workflow for the
detection of BRCA1 and BRCA2 mutations using massive parallel sequencing in a 454
GS Junior bench top sequencer. Our approach was first validated in a panel of 23
patients containing 62 unique variants that had been previously Sanger sequenced.
Subsequently, 101 patients with familial breast and ovarian cancer were studied.
BRCA1 and BRCA2 exon enrichment has been performed by PCR amplification using the
BRCA MASTR kit (Multiplicom). Bioinformatic analysis of reads is performed with
the AVA software v2.7 (Roche). In total, all 62 variants were detected resulting
in a sensitivity of 100%. 71 false positives were called resulting in a
specificity of 97.35%. All of them correspond to deletions located in
homopolymeric stretches. The analysis of the homopolymers stretches of 6 bp or
longer using the BRCA HP kit (Multiplicom) increased the specificity of the
detection of BRCA1 and BRCA2 mutations to 99.99%. We show here that massive
parallel pyrosequencing can be used as a diagnostic strategy to test for BRCA1
and BRCA2 mutations meeting very stringent sensitivity and specificity parameters
replacing traditional Sanger sequencing with a lower cost.
PMID- 25136595
TI - Effect of glass fiber incorporation on flexural properties of experimental
composites.
AB - This study evaluated the effect of fiber addiction in flexural properties of 30
wt% silica filled BisGMA resin (FR) or unfilled Bis-GMA (UR). Ten groups were
created (N = 10) varying the resin (FR or UR) and quantity of glass fibers (wt%:
0, 10, 15, 20, and 30). Samples (10 * 2 * 1 mm) were submitted to flexural
strength test following SEM examination. Data were analyzed by two-way ANOVA,
Tukey, and Student t-test (alpha = 0.05). Results for flexural strength (MPa)
were FR-groups: 0% (442.7 +/- 140.6)(C), 10% (772.8 +/- 446.3)(ABC), 15% (854.7
+/- 297.3)(AB), 20% (863.4 +/- 418.0)(A), 30% (459.5 +/- 140.5)(BC); UR-groups:
0% (187.7 +/- 120.3)(B), 10% (795.4 +/- 688.1)(B), 15% (1999.9 +/- 1258.6)(A),
20% (1911.5 +/- 596.8)(A), and 30% (2090.6 +/- 656.7)(A), and for flexural
modulus (GPa) FR-groups: 0% (2065.63 +/- 882.15)(B), 10% (4479.06 +/-
3019.82)(AB), 15% (5694.89 +/- 2790.3)(A), 20% (6042.11 +/- 3392.13)(A), and 30%
(2495.67 +/- 1345.86)(B); UR-groups: 0% (1090.08 +/- 708.81)(C), 10% (7032.13 +/-
7864.53)(BC), 15% (19331.57 +/- 16759.12)(AB), 20% (15726.03 +/- 8035.09)(AB),
and 30% (29364.37 +/- 13928.96)(A). Fiber addiction in BisGMA resin increases
flexural properties, and the interaction between resin and fibers seems better in
the absence of inorganic fillers increasing flexural properties.
PMID- 25136593
TI - Microenvironment, oncoantigens, and antitumor vaccination: lessons learned from
BALB-neuT mice.
AB - The tyrosine kinase human epidermal growth factor receptor 2 (HER2) gene is
amplified in approximately 20% of human breast cancers and is associated with an
aggressive clinical course and the early development of metastasis. Its crucial
role in tumor growth and progression makes HER2 a prototypic oncoantigen, the
targeting of which may be critical for the development of effective anticancer
therapies. The setup of anti-HER2 targeting strategies has revolutionized the
clinical outcome of HER2(+) breast cancer. However, their initial success has
been overshadowed by the onset of pharmacological resistance that renders them
ineffective. Since the tumor microenvironment (TME) plays a crucial role in drug
resistance, the design of more effective anticancer therapies should depend on
the targeting of both cancer cells and their TME as a whole. In this review,
starting from the successful know-how obtained with a HER2(+) mouse model of
mammary carcinogenesis, the BALB-neuT mice, we discuss the role of TME in mammary
tumor development. Indeed, a deeper knowledge of antigens critical for cancer
outbreak and progression and of the mechanisms that regulate the interplay
between cancer and stromal cell populations could advise promising ways for the
development of the best anticancer strategy.
PMID- 25136597
TI - Management of the bleeding patient receiving new oral anticoagulants: a role for
prothrombin complex concentrates.
AB - Ease of dosing and simplicity of monitoring make new oral anticoagulants an
attractive therapy in a growing range of clinical conditions. However, newer oral
anticoagulants interact with the coagulation cascade in different ways than
traditional warfarin therapy. Replacement of clotting factors will not reverse
the effects of dabigatran, rivaroxaban, or apixaban. Currently, antidotes for
these drugs are not widely available. Fortunately, withholding the anticoagulant
and dialysis are freqnently effective treatments, particularly with rivaroxaban
and dabigatran. Emergent bleeding, however, requires utilization of Prothrombin
Complex Concentrates (PCCs). PCCs, in addition to recombinant factor VIIa, are
used to activate the clotting system to reverse the effects of the new oral
anticoagulants. In cases of refractory or emergent bleeding, the recommended
factor concentrate in our protocols differs between the new oral anticoagulants.
In patients taking dabigatran, we administer an activated PCC (aPCC) [FELBA] due
to reported benefit in human in vitro studies. Based on human clinical trial
evidence, the 4-factor PCC (Kcentra) is suggested for patients with refractory
rivaroxaban- or apixaban-associated hemorrhage. If bleeding continues,
recombinant factor VIIa may be employed. With all of these new procoagulant
agents, the risk of thrombosis associated with administration of factor
concentrates must be weighed against the relative risk of hemorrhage.
PMID- 25136596
TI - Synergistic effects of toxic elements on heat shock proteins.
AB - Heat shock proteins show remarkable variations in their expression levels under a
variety of toxic conditions. A research span expanded over five decades has
revealed their molecular characterization, gene regulation, expression patterns,
vast similarity in diverse groups, and broad range of functional capabilities.
Their functions include protection and tolerance against cytotoxic conditions
through their molecular chaperoning activity, maintaining cytoskeleton stability,
and assisting in cell signaling. However, their role as biomarkers for monitoring
the environmental risk assessment is controversial due to a number of
conflicting, validating, and nonvalidating reports. The current knowledge
regarding the interpretation of HSPs expression levels has been discussed in the
present review. The candidature of heat shock proteins as biomarkers of toxicity
is thus far unreliable due to synergistic effects of toxicants and other
environmental factors. The adoption of heat shock proteins as "suit of biomarkers
in a set of organisms" requires further investigation.
PMID- 25136598
TI - Hox transcription factors: modulators of cell-cell and cell-extracellular matrix
adhesion.
AB - Hox genes encode homeodomain-containing transcription factors that determine cell
and tissue identities in the embryo during development. Hox genes are also
expressed in various adult tissues and cancer cells. In Drosophila, expression of
cell adhesion molecules, cadherins and integrins, is regulated by Hox proteins
operating in hierarchical molecular pathways and plays a crucial role in segment
specific organogenesis. A number of studies using mammalian cultured cells have
revealed that cell adhesion molecules responsible for cell-cell and cell
extracellular matrix interactions are downstream targets of Hox proteins.
However, whether Hox transcription factors regulate expression of cell adhesion
molecules during vertebrate development is still not fully understood. In this
review, the potential roles Hox proteins play in cell adhesion and migration
during vertebrate body patterning are discussed.
PMID- 25136599
TI - Recombinant lysostaphin protects mice from methicillin-resistant Staphylococcus
aureus pneumonia.
AB - The advent of methicillin-resistant Staphylococcus aureus (MRSA) and the frequent
and excessive abuse of ventilators have made MRSA pneumonia an inordinate threat
to human health. Appropriate antibacterial therapies are crucial, including the
use of lysostaphin as an alternative to antibiotics. To explore the potential use
of lysostaphin as a therapeutic agent for MRSA pneumonia, mice were intranasally
infected with MRSA and then treated with recombinant lysostaphin (rLys; 45 mg/kg
in the high-dose group and 1 mg/kg in the low-dose group) (0.33 mg/mL, 15 mg/mL),
vancomycin (120 mg/kg) (40 mg/mL), or phosphate-buffered saline (PBS, negative
control) 4 h after infection. Therapeutic efficacy was assessed by mouse
survival, lung histopathology, bacterial density in the lungs, bodyweight, lung
weight, temperature, white blood cells counts, lymphocytes counts, granulocytes
counts, and monocytes counts. The mice treated with rLys showed lower mortality,
less lung parenchymal damage, and lower bacterial density at metastatic tissue
sites than mice treated with PBS or vancomycin. The overall mortality was 100%,
60%, 40%, and 60% for the control, vancomycin, high-dose rLys, and low-dose rLys
groups, respectively. These findings indicate that, as a therapeutic agent for
MRSA pneumonia, lysostaphin exerts profound protective effects in mice against
the morbidity and mortality associated with S. aureus pneumonia.
PMID- 25136600
TI - Total bolus extraction method improves arterial image quality in dynamic CTAs
derived from whole-brain CTP data.
AB - Background and Purposes. The 320-detector row CT scanner enables visualization of
whole-brain hemodynamic information (dynamic CT angiography (CTA) derived from CT
perfusion scans). However, arterial image quality in dynamic CTA (dCTA) is
inferior to arterial image quality in standard CTA. This study evaluates whether
the arterial image quality can be improved by using a total bolus extraction
(ToBE) method. Materials and Methods. DCTAs of 15 patients, who presented with
signs of acute cerebral ischemia, were derived from 320-slice CT perfusion scans
using both the standard subtraction method and the proposed ToBE method. Two
neurointerventionalists blinded to the scan type scored the arterial image
quality on a 5-point scale in the 4D dCTAs in consensus. Arteries were divided
into four categories: (I) large extradural, (II) intradural (large, medium, and
small), (III) communicating arteries, and (IV) cerebellar and ophthalmic
arteries. Results. Quality of extradural and intradural arteries was
significantly higher in the ToBE dCTAs than in the standard dCTAs (extradural P =
0.001, large intradural P < 0.001, medium intradural P < 0.001, and small
intradural P < 0.001). Conclusion. The 4D dCTAs derived with the total bolus
extraction (ToBE) method provide hemodynamic information combined with improved
arterial image quality as compared to standard 4D dCTAs.
PMID- 25136601
TI - Immune response, safety, and survival and quality of life outcomes for advanced
colorectal cancer patients treated with dendritic cell vaccine and cytokine
induced killer cell therapy.
AB - PURPOSE: To determine the immune response after dendritic cell (DC) vaccine and
cytokine-induced killer cells (CIK) therapy and assess its associated toxicity,
survival benefit, and changes in the quality of life (QOL) of advanced colorectal
cancer (CRC) patients. METHODS: We recruited 100 patients with unresectable CRC
orrelapsed CRC after surgery who received DC vaccine and CIK cells (group
immunotherapy, group I), and, as a control, 251 patients who had similar
characteristics and underwent similar treatments, except for this immunotherapy
(group nonimmunotherapy, group NI). After a follow-up period of 489.2 +/- 160.4
days, overall survival (OS) of the two groups was compared using the Kaplan-Meier
method. RESULTS: In group I, 62% of patients developed a positive delayed type
hypersensitivity response, and most patients showed an improvement in physical
strength (75.2%), appetite (74.2%), sleeping (72.1%), and body weight (70.1%).
Adverse events were fever (29.5%), insomnia (19.2%), anorexia (9.1%), sore joints
(5.4%), and skin rash (1.0%). No toxicity was observed in patients treated with
DC vaccine and CIK therapy. OS was significantly longer in group I than in group
NI (P = 0.043). CONCLUSION: DC vaccine and CIK therapy were safe and could induce
an immune response against CRC, thereby improving QOL and prolonging OS.
PMID- 25136602
TI - Effect of cocoa butter and sunflower oil supplementation on performance,
immunoglobulin, and antioxidant vitamin status of rats.
AB - This study investigated the effects of cocoa butter and sunflower oil alone and
in combination on performance, some biochemical parameters, immunoglobulin, and
antioxidant vitamin status in Wistar rats. Forty-eight male rats were assigned to
four groups, consisting of 12 rats with 3 replicates. Control received balanced
rat diet without oil, cocoa butter group received 3.5% cocoa butter, sunflower
oil group received 3.5% sunflower oil, the last group received 1.75% sunflower
oil + 1.75% cocoa butter supplementation in the rat diet for 8 weeks. The total
feed consumption in sunflower oil group was statistically lower than in the other
groups. The serum creatinine level was decreased in cocoa butter group compared
to control. Triglyceride and VLDL cholesterol levels were decreased in only
sunflower oil and only cocoa butter groups as compared to control. The level of
Ig M was statistically lower in cocoa butter and cocoa butter + sunflower oil
groups than in control and sunflower oil groups. There were no statistically
important difference in vitamin concentrations among trial groups. It was
concluded that the supplementation of cocoa butter in diet decreased Ig M level,
while the supplementation of cocoa butter and sunflower oil alone decreased the
triglyceride and VLDL cholesterol levels.
PMID- 25136603
TI - Anterior segment optical coherence tomography imaging of conjunctival filtering
blebs after glaucoma surgery.
AB - Time domain (TD) and spectral domain (SD) optical coherence tomography (OCT) are
cross-sectional, noncontact, high-resolution diagnostic modalities for posterior
and anterior segment (AS) imaging. The AS-OCT provides tomographic imaging of the
cornea, iris, lens, and anterior chamber (AC) angle in several ophthalmic
diseases. In glaucoma, AS-OCT is utilized to evaluate the morphology of AS
structures involved in the pathogenesis of the disease, to obtain morphometric
measures of the AC, to evaluate the suitability for laser or surgical approaches,
and to assess modifications after treatment. In patients undergoing surgery, AS
OCT is crucial in the evaluation of the filtering bleb functionality, permitting
a combined qualitative and quantitative analysis. In this field, AS-OCT may help
clinicians in distinguishing between functioning and nonfunctioning blebs by
classifying their macroscopic morphology, describing bleb-wall features, bleb
cavity, and scleral opening. This information is critical in recognizing signs of
filtration failure earlier than the clinical approach and in planning the
appropriate timing for management procedures in failing blebs. In this review, we
summarize the applications of AS-OCT in the conjunctival bleb assessment.
PMID- 25136605
TI - Computational analysis of the model describing HIV infection of CD4+T Cells.
AB - An analysis of the model underpinning the description of the spread of HIV
infection of CD4(+)T cells is examined in detail in this work. Investigations of
the disease free and endemic equilibrium are done using the method of Jacobian
matrix. An iteration technique, namely, the homotopy decomposition method (HDM),
is implemented to give an approximate solution of nonlinear ordinary differential
equation systems. The technique is described and illustrated with numerical
examples. The approximated solution obtained via HDM is compared with those
obtained via other methods to prove the trustworthiness of HDM. Moreover, the
lessening and simplicity in calculations furnish HDM with a broader
applicability.
PMID- 25136604
TI - Disruption of HPV16-E7 by CRISPR/Cas system induces apoptosis and growth
inhibition in HPV16 positive human cervical cancer cells.
AB - High-risk human papillomavirus (HR-HPV) has been recognized as a major causative
agent for cervical cancer. Upon HPV infection, early genes E6 and E7 play
important roles in maintaining malignant phenotype of cervical cancer cells. By
using clustered regularly interspaced short palindromic repeats- (CRISPR-)
associated protein system (CRISPR/Cas system), a widely used genome editing tool
in many organisms, to target HPV16-E7 DNA in HPV positive cell lines, we showed
for the first time that the HPV16-E7 single-guide RNA (sgRNA) guided CRISPR/Cas
system could disrupt HPV16-E7 DNA at specific sites, inducing apoptosis and
growth inhibition in HPV positive SiHa and Caski cells, but not in HPV negative
C33A and HEK293 cells. Moreover, disruption of E7 DNA directly leads to
downregulation of E7 protein and upregulation of tumor suppressor protein pRb.
Therefore, our results suggest that HPV16-E7 gRNA guided CRISPR/Cas system might
be used as a therapeutic strategy for the treatment of cervical cancer.
PMID- 25136606
TI - Inference of SNP-gene regulatory networks by integrating gene expressions and
genetic perturbations.
AB - In order to elucidate the overall relationships between gene expressions and
genetic perturbations, we propose a network inference method to infer gene
regulatory network where single nucleotide polymorphism (SNP) is involved as a
regulator of genes. In the most of the network inferences named as SNP-gene
regulatory network (SGRN) inference, pairs of SNP-gene are given by separately
performing expression quantitative trait loci (eQTL) mappings. In this paper, we
propose a SGRN inference method without predefined eQTL information assuming a
gene is regulated by a single SNP at most. To evaluate the performance, the
proposed method was applied to random data generated from synthetic networks and
parameters. There are three main contributions. First, the proposed method
provides both the gene regulatory inference and the eQTL identification. Second,
the experimental results demonstrated that integration of multiple methods can
produce competitive performances. Lastly, the proposed method was also applied to
psychiatric disorder data in order to explore how the method works with real
data.
PMID- 25136607
TI - Clinical applications of end-to-side neurorrhaphy: an update.
AB - End-to-side neurorrhaphy constitutes an interesting option to regain nerve
function after damage in selected cases, in which conventional techniques are not
feasible. In the last twenty years, many experimental and clinical studies have
been conducted in order to understand the biological mechanisms and to test the
effectiveness of this technique, with contrasting results. In this updated
review, we consider the state of the art about end-to-side coaptation, focusing
on all the current clinical applications, such as sensory and mixed nerve repair,
treatment of facial palsy, and brachial plexus injuries and painful neuromas
management.
PMID- 25136608
TI - Ruscogenin ameliorates experimental nonalcoholic steatohepatitis via suppressing
lipogenesis and inflammatory pathway.
AB - The aim of the study was to investigate the protective effects of ruscogenin, a
major steroid sapogenin in Ophiopogon japonicus, on experimental models of
nonalcoholic steatohepatitis. HepG2 cells were exposed to 300 MUmol/l palmitic
acid (PA) for 24 h with the preincubation of ruscogenin for another 24 h.
Ruscogenin (10.0 MUmol/l) had inhibitory effects on PA-induced triglyceride
accumulation and inflammatory markers in HepG2 cells. Male golden hamsters were
randomly divided into five groups fed a normal diet, a high-fat diet (HFD), or a
HFD supplemented with ruscogenin (0.3, 1.0, or 3.0 mg/kg/day) by gavage once
daily for 8 weeks. Ruscogenin alleviated dyslipidemia, liver steatosis, and
necroinflammation and reversed plasma markers of metabolic syndrome in HFD-fed
hamsters. Hepatic mRNA levels involved in fatty acid oxidation were increased in
ruscogenin-treated HFD-fed hamsters. Conversely, ruscogenin decreased expression
of genes involved in hepatic lipogenesis. Gene expression of inflammatory
cytokines, chemoattractive mediator, nuclear transcription factor-(NF-) kappaB,
and alpha-smooth muscle actin were increased in the HFD group, which were
attenuated by ruscogenin. Ruscogenin may attenuate HFD-induced steatohepatitis
through downregulation of NF-kappaB-mediated inflammatory responses, reducing
hepatic lipogenic gene expression, and upregulating proteins in beta-oxidation
pathway.
PMID- 25136609
TI - IOL power calculation after corneal refractive surgery.
AB - PURPOSE: To describe the different formulas that try to overcome the problem of
calculating the intraocular lens (IOL) power in patients that underwent corneal
refractive surgery (CRS). METHODS: A Pubmed literature search review of all
published articles, on keyword associated with IOL power calculation and corneal
refractive surgery, as well as the reference lists of retrieved articles, was
performed. RESULTS: A total of 33 peer reviewed articles dealing with methods
that try to overcome the problem of calculating the IOL power in patients that
underwent CRS were found. According to the information needed to try to overcome
this problem, the methods were divided in two main categories: 18 methods were
based on the knowledge of the patient clinical history and 15 methods that do not
require such knowledge. The first group was further divided into five subgroups
based on the parameters needed to make such calculation. CONCLUSION: In the light
of our findings, to avoid postoperative nasty surprises, we suggest using only
those methods that have shown good results in a large number of patients,
possibly by averaging the results obtained with these methods.
PMID- 25136610
TI - Blood vessel-derived acellular matrix for vascular graft application.
AB - To overcome the issues connected to the use of autologous vascular grafts and
artificial materials for reconstruction of small diameter (<6 mm) blood vessels,
this study aimed to develop acellular matrix- (AM-) based vascular grafts. Rat
iliac arteries were decellularized by a detergent-enzymatic treatment, whereas
endothelial cells (ECs) were obtained through enzymatic digestion of rat skin
followed by immunomagnetic separation of CD31-positive cells. Sixteen female
Lewis rats (8 weeks old) received only AM or previously in vitro
reendothelialized AM as abdominal aorta interposition grafts (about 1 cm). The
detergent-enzymatic treatment completely removed the cellular part of vessels and
both MHC class I and class II antigens. One month after surgery, the luminal
surface of implanted AMs was partially covered by ECs and several platelets
adhered in the areas lacking cell coverage. Intimal hyperplasia, already detected
after 1 month, increased at 3 months. On the contrary, all grafts composed by AM
and ECs were completely covered at 1 month and their structure was similar to
that of native vessels at 3 months. Taken together, our findings show that
prostheses composed of AM preseeded with ECs could be a promising approach for
the replacement of blood vessels.
PMID- 25136612
TI - Efficient expression of acetylcholine-binding protein from Aplysia californica in
Bac-to-Bac system.
AB - The Bac-to-Bac baculovirus expression system can efficiently produce recombinant
proteins, but the system may have to be optimized to achieve high-level
expression for different candidate proteins. We reported here the efficient
expression of acetylcholine-binding proteins from sea hares Aplysia californica
(Ac-AChBP) and a convenient method to monitor protein expression level in this
expression system. Three key factors affecting expression of Ac-AChBP were
optimized for maximizing the yield, which included the cell density, volume of
the infecting baculovirus inoculums, and the culturing time of postinfection. We
have found it to reach a high yield of ~5 mg/L, which needs 55 h incubation after
infection at the cell density of 2 * 10(6) cells/mL with an inoculum volume ratio
of 1 : 100. The optimized expression system in this study was also applied for
expressing another protein Ls-AChBP from Lymnaea stagnalis successfully.
Therefore, this established method is helpful to produce high yields of AChBP
proteins for X-ray crystallographic structural and functional studies.
PMID- 25136611
TI - Alternative splicing generates different parkin protein isoforms: evidences in
human, rat, and mouse brain.
AB - Parkinson protein 2, E3 ubiquitin protein ligase (PARK2) gene mutations are the
most frequent causes of autosomal recessive early onset Parkinson's disease and
juvenile Parkinson disease. Parkin deficiency has also been linked to other human
pathologies, for example, sporadic Parkinson disease, Alzheimer disease, autism,
and cancer. PARK2 primary transcript undergoes an extensive alternative splicing,
which enhances transcriptomic diversification. To date several PARK2 splice
variants have been identified; however, the expression and distribution of parkin
isoforms have not been deeply investigated yet. Here, the currently known PARK2
gene transcripts and relative predicted encoded proteins in human, rat, and mouse
are reviewed. By analyzing the literature, we highlight the existing data showing
the presence of multiple parkin isoforms in the brain. Their expression emerges
from conflicting results regarding the electrophoretic mobility of the protein,
but it is also assumed from discrepant observations on the cellular and tissue
distribution of parkin. Although the characterization of each predicted isoforms
is complex, since they often diverge only for few amino acids, analysis of their
expression patterns in the brain might account for the different pathogenetic
effects linked to PARK2 gene mutations.
PMID- 25136613
TI - Does platelet-rich plasma freeze-thawing influence growth factor release and
their effects on chondrocytes and synoviocytes?
AB - PRP cryopreservation remains a controversial point. Our purpose was to
investigate the effect of freezing/thawing on PRP molecule release, and its
effects on the metabolism of chondrocytes and synoviocytes. PRP was prepared from
10 volunteers, and a half volume underwent one freezing/thawing cycle. IL-1beta,
HGF, PDGF AB/BB, TGF-beta1, and VEGF were assayed 1 hour and 7 days after
activation. Culture media of chondrocytes and synoviocytes were supplemented with
fresh or frozen PRP, and, at 7 days, proliferation, gene expression, and secreted
proteins levels were evaluated. Results showed that in the freeze-thawed PRP the
immediate and delayed molecule releases were similar or slightly lower than those
in fresh PRP. TGF-beta1 and PDGF AB/BB concentrations were significantly reduced
after freezing both at 1 hour and at 7 days, whereas HGF concentration was
significantly lower in frozen PRP at 7 days. In fresh PRP IL-1beta and HGF
concentrations underwent a significant further increase after 7 days. Similar
gene expression was found in chondrocytes cultured with both PRPs, whereas in
synoviocytes HGF gene expression was higher in frozen PRP. PRP cryopreservation
is a safe procedure, which sufficiently preserves PRP quality and its ability to
induce proliferation and the production of ECM components in chondrocytes and
synoviocytes.
PMID- 25136614
TI - Intensive insulin therapy for septic patients: a meta-analysis of randomized
controlled trials.
AB - Background. Studies on the effect of intensive insulin therapy (IIT) in septic
patients with hyperglycemia have given inconsistent results. The primary purpose
of this meta-analysis was to evaluate whether it is effective in reducing
mortality. Methods. We searched PubMed, Embase, the Cochrane Library,
clinicaltrials.gov, and relevant reference lists up to September 2013 and
including randomized controlled trials that compared IIT with conventional
glucose management in septic patients. Study quality was assessed using the
Cochrane Risk of Bias Tool. And our primary outcome measure was pooled in the
random effects model. Results. We identified twelve randomized controlled trials
involving 4100 patients. Meta-analysis showed that IIT did not reduce any of the
outcomes: overall mortality (risk ratio [RR] = 0.98, 95% CI [0.85, 1.15], P =
0.84), 28-day mortality (RR = 0.66, 95% CI [0.40, 1.10], P = 0.11), 90-day
mortality (RR = 1.10, 95% CI [0.97, 1.26], P = 0.13), ICU mortality (RR = 0.94,
95% CI [0.77, 1.14], P = 0.52), hospital mortality (RR = 0.98, 95% CI [0.86,
1.11], P = 0.71), severity of illness, and length of ICU stay. Conversely, the
incidence of hypoglycemia was markedly higher in the IIT (RR = 2.93, 95% CI
[1.69, 5.06], P = 0.0001). Conclusions. For patients with sepsis, IIT and
conservative glucose management show similar efficacy, but ITT is associated with
a higher incidence of hypoglycemia.
PMID- 25136615
TI - Human endogenous retrovirus W activity in cartilage of osteoarthritis patients.
AB - The etiology of viruses in osteoarthritis remains controversial because the
prevalence of viral nucleic acid sequences in peripheral blood or synovial fluid
from osteoarthritis patients and that in healthy control subjects are similar.
Until now the presence of virus has not been analyzed in cartilage. We screened
cartilage and chondrocytes from advanced and non-/early osteoarthritis patients
for parvovirus B19, herpes simplex virus-1, Epstein Barr virus, cytomegalovirus,
human herpes virus-6, hepatitis C virus, and human endogenous retroviruses
transcripts. Endogenous retroviruses transcripts, but none of the other viruses,
were detected in 15 out the 17 patients. Sequencing identified the virus as HERV
WE1 and E2. HERV-W activity was confirmed by high expression levels of syncytin,
dsRNA, virus budding, and the presence of virus-like particles in all advanced
osteoarthritis cartilages examined. Low levels of HERV-WE1, but not E2 envelope
RNA, were observed in 3 out of 8 non-/early osteoarthritis patients, while only 3
out of 7 chondrocytes cultures displayed low levels of syncytin, and just one was
positive for virus-like particles. This study demonstrates for the first time
activation of HERV-W in cartilage of osteoarthritis patients; however, a
causative role for HERV-W in development or deterioration of the disease remains
to be proven.
PMID- 25136616
TI - Description of a novel adhesin of Mycobacterium avium subsp. paratuberculosis.
AB - The binding and ingestion of Mycobacterium avium subsp. paratuberculosis (MAP) by
host cells are fibronectin (FN) dependent. In several species of mycobacteria, a
specific family of proteins allows the attachment and internalization of these
bacteria by epithelial cells through interaction with FN. Thus, the
identification of adhesion molecules is essential to understand the pathogenesis
of MAP. The aim of this study was to identify and characterize FN binding cell
wall proteins of MAP. We searched for conserved adhesins within a large panel of
surface immunogenic proteins of MAP and investigated a possible interaction with
FN. For this purpose, a cell wall protein fraction was obtained and resolved by
2D electrophoresis. The immunoreactive spots were identified by MALDI-TOF MS and
a homology search was performed. We selected elongation factor Tu (EF-Tu) as
candidate for further studies. We demonstrated the FN-binding capability of EF-Tu
using a ligand blot assay and also confirmed the interaction with FN in a dose
dependent manner by ELISA. The dissociation constant of EF-Tu was determined by
surface plasmon resonance and displayed values within the MUM range. These data
support the hypothesis that this protein could be involved in the interaction of
MAP with epithelial cells through FN binding.
PMID- 25136617
TI - Chemical composition, leishmanicidal and cytotoxic activities of the essential
oils from Mangifera indica L. var. Rosa and Espada.
AB - The essential oils from Mangifera indica var. Rosa and Espada latex were obtained
by hydrodistillation and analyzed using GC-FID and GC-MS. Twenty-seven components
were identified. The main compound in the essential oil from M. indica var.
Espada (EOMiE) was terpinolene (73.6%). The essential oil of M. indica var. Rosa
(EOMiR) was characterized by high amounts of beta-pinene (40.7%) and terpinolene
(28.3%). In the test for leishmanicidal activity against promastigotes forms of
L. amazonensis, EOMiR and EOMiE showed IC50 (72 h) of 39.1 and 23.0 MUg/mL,
respectively. In macrophages, EOMiR and EOMiE showed CC50 of 142.84 and 158.65
MUg/mL, respectively. However, both were more specific to the parasite than
macrophages, with values of selectivity index of 6.91 for EOMiE and 3.66 for
EOMiR. The essential oils were evaluated for their cytotoxicity against the human
tumor cells HEp-2, HT-29, NCI-H292, and HL-60. The EOMiR and EOMiE were most
effective against the HL-60, with IC50 values of 12.3 and 3.6 MUg/mL,
respectively. The results demonstrated that the essential oils of M. indica can
destroy L. amazonensis and inhibit tumor cell growth. These findings contribute
to the knowledge of the Brazilian biodiversity as a source of potential
therapeutic agents.
PMID- 25136618
TI - The prognostic and risk-stratified value of heart-type fatty-acid-binding protein
in community acquired pneumonia in emergency department.
AB - OBJECTIVE: To evaluate the prognostic and risk stratified ability of heart-type
fatty-acid-binding protein (H-FABP) in patients with community acquired pneumonia
(CAP) in emergency department (ED) and to compare it with Pneumonia Severity
Index (PSI) and CURB-65. METHODS: Consecutive adult CAP patients admitted to the
ED of Beijing Chao-Yang Hospital were enrolled. Circulating H-FABP and troponin I
were measured. PSI and CURB-65 were calculated in all patients. The differences
in 28-day mortality and requirement for mechanical ventilation (MV) or a
vasopressor within 6 h after ED arrival were compared in patients with positive H
FABP (>=7 ng/mL) and negative ones (<7 ng/mL). Receiver operating characteristic
(ROC) curve and logistic regression were used to assess the predictive value of H
FABP. RESULTS: From August to November 2012, 229 CAP patients were enrolled. The
28-day mortality, PSI, CURB-65, and incidence of using MV or a vasopressor were
much higher in H-FABP-positive patients than in negative ones (P < 0.01). H-FABP
was an independent predictor of the 28-day mortality. The area under the ROC
curve (AUC) of H-FABP was 0.751. Combination of H-FABP and CURB-65 (AUC = 0.824)
or H-FABP and PSI (AUC = 0.820) improved their prognostic performance.
CONCLUSIONS: H-FABP was valuable for prognosis and risk stratification in CAP
patients in ED.
PMID- 25136619
TI - Comparison of reaction response time between hand and foot controlled devices in
simulated microsurgical testing.
AB - PURPOSE: We hypothesized that reaction times (RTs) for a switch release are
faster for hand-controlled than for foot-controlled switches for physiological
and anatomical reasons (e.g., nerve conduction speed). The risk of accidental
trauma could be reduced if the surgeon reacted quicker and therefore improve the
surgical outcome. METHOD: We included 47 medical professionals at USC.
Demographics and handedness were recorded. Under a microscope, a simple reaction
time test was performed, testing all extremities multiple times in a random
order. Additionally, a subjective questionnaire was administered. RESULTS: The
mean RTs for hands are 318.24 ms +/- 51.13 and feet 328.69 +/- 48.70. The
comparison of hand versus foot showed significant shorter RTs for the hand (P =
0.025). Partially significant differences between and within the experience level
groups could be demonstrated by level of education (LE) and microscopic
surgeries/week (MSW) (P = 0.57-0.02). In the subjective questionnaire, 91.5% (n =
43/47) of test subjects prefer to use hand controls. CONCLUSION: Our data show
that the RT for hands is faster than feet. Similarly the subjective questionnaire
showed a greater preference for hand actuation. This data suggest a hand
controlled ophthalmic instrument might have distinct advantages; however,
clinical correlation is required.
PMID- 25136620
TI - Epidemiology, phylogeny, and evolution of emerging enteric Picobirnaviruses of
animal origin and their relationship to human strains.
AB - Picobirnavirus (PBV) which has been included in the list of viruses causing
enteric infection in animals is highly versatile because of its broad host range
and genetic diversity. PBVs are among the most recent and emerging small,
nonenveloped viruses with a bisegmented double-stranded RNA genome, classified
under a new family "Picobirnaviridae." PBVs have also been detected from
respiratory tract of pigs, but needs further close investigation for their
inhabitant behavior. Though, accretion of genomic data of PBVs from different
mammalian species resolved some of the ambiguity, quite a few questions and
hypotheses regarding pathogenesis, persistence location, and evolution of PBVs
remain unreciprocated. Evolutionary analysis reveals association of PBVs with
partitiviruses especially fungi partitiviruses. Although, PBVs may have an
ambiguous clinical implication, they do pose a potential public health concern in
humans and control of PBVs mainly relies on nonvaccinal approach. Based upon the
published data, from 1988 to date, generated from animal PBVs across the globe,
this review provides information and discussion with respect to genetic analysis
as well as evolution of PBVs of animal origin in relation to human strains.
PMID- 25136621
TI - Obligatory role for endothelial heparan sulphate proteoglycans and caveolae
internalization in catestatin-dependent eNOS activation.
AB - The chromogranin-A peptide catestatin modulates a wide range of processes, such
as cardiovascular functions, innate immunity, inflammation, and metabolism. We
recently found that the cardiac antiadrenergic action of catestatin requires a
PI3K-dependent NO release from endothelial cells, although the receptor involved
is yet to be identified. In the present work, based on the cationic properties of
catestatin, we tested the hypothesis of its interaction with membrane heparan
sulphate proteoglycans, resulting in the activation of a caveolae-dependent
endocytosis. Experiments were performed on bovine aortic endothelial cells.
Endocytotic vesicles trafficking was quantified by confocal microscopy using a
water-soluble membrane dye; catestatin colocalization with heparan sulphate
proteoglycans and caveolin 1 internalization were studied by fluorimetric
measurements in live cells. Modulation of the catestatin-dependent eNOS
activation was assessed by immunofluorescence and immunoblot analysis. Our
results demonstrate that catestatin (5 nM) colocalizes with heparan sulphate
proteoglycans and induces a remarkable increase in the caveolae-dependent
endocytosis and caveolin 1 internalization, which were significantly reduced by
both heparinase and wortmannin. Moreover, catestatin was unable to induce
Ser(1179) eNOS phosphorylation after pretreatments with heparinase and methyl
beta-cyclodextrin. Taken together, these results highlight the obligatory role
for proteoglycans and caveolae internalization in the catestatin-dependent eNOS
activation in endothelial cells.
PMID- 25136622
TI - Preclinical and clinical effects of mistletoe against breast cancer.
AB - Breast cancer is among the most frequent types of cancer in women worldwide.
Current conventional treatment options are accompanied by side effects. Mistletoe
is amongst the important herbal medicines traditionally used as complementary
remedies. An increasing number of studies have reported anticancer activity of
mistletoe extracts on breast cancer cells and animal models. Some recent evidence
suggests that cytotoxic activity of mistletoe may be mediated through different
mechanisms. These findings provide a good base for clinical trials. Various
studies on mistletoe therapy for breast cancer patients revealed similar findings
concerning possible benefits on survival time, health-related quality of life
(HRQoL), remission rate, and alleviating adverse reactions to conventional
therapy. This review provides an overview of the recent findings on preclinical
experiments and clinical trials of mistletoe for its cytotoxic and antitumor
activity and its effect on HRQoL in breast cancer patients. Moreover, studies
investigating molecular and cellular mechanisms underlying antitumor activity of
mistletoe are discussed in this paper. The analyzed trials provided evidence that
there might be a combination of pharmacological and motivational aspects mediated
by the mistletoe extract application which may contribute to the clinical benefit
and positive outcome such as improved HRQoL and self-regulation in breast cancer
patients.
PMID- 25136624
TI - Modified titanium implant as a gateway to the human body: the implant mediated
drug delivery system.
AB - The aim of this study was to investigate the efficacy of a proposed new implant
mediated drug delivery system (IMDDS) in rabbits. The drug delivery system is
applied through a modified titanium implant that is configured to be implanted
into bone. The implant is hollow and has multiple microholes that can
continuously deliver therapeutic agents into the systematic body. To examine the
efficacy and feasibility of the IMDDS, we investigated the pharmacokinetic
behavior of dexamethasone in plasma after a single dose was delivered via the
modified implant placed in the rabbit tibia. After measuring the plasma
concentration, the areas under the curve showed that the IMDDS provided a
sustained release for a relatively long period. The result suggests that the
IMDDS can deliver a sustained release of certain drug components with a high
bioavailability. Accordingly, the IMDDS may provide the basis for a novel
approach to treating patients with chronic diseases.
PMID- 25136625
TI - The type of fat ingested at breakfast influences the plasma lipid profile of
postmenopausal women.
AB - To assess whether the type of fat ingested at breakfast can modify the plasma
lipid profile and other cardiovascular risk variables in postmenopausal women at
risk of cardiovascular disease, a longitudinal, randomized, and crossover study
was carried out with postmenopausal women at risk of CVD. They were randomly
assigned to eat each type of breakfast during one month: 6 study periods
(breakfast with the same composition plus butter/margarine/virgin olive oil)
separated by two washout periods. On the first and last days of each study
period, weight, arterial blood pressure, heart rate, and body mass index were
recorded in fasting conditions and a blood sample was collected to measure plasma
lipid profile. When comparing final values to baseline values, we only found out
statistically significant differences on plasma lipid profiles. Butter-based
breakfast increased total cholesterol and HDL, while margarine-based breakfast
decreased total cholesterol and LDL and increased HDL. After the olive oil-based
breakfast intake, a tendency towards a decrease of total cholesterol and LDL
levels and an increase of HDL levels was observed. No statistically significant
differences were observed in triglycerides levels, BMI, and arterial pressure in
any breakfast type. The margarine-based breakfast was the only one which
significantly increased the percentage of volunteers with optimal lipid profiles.
The polyunsaturated fat at breakfast has improved the plasma lipid profile in the
analyzed sample population, suggesting that PUFA-based breakfast can be advisable
in women at risk of CVD.
PMID- 25136623
TI - BRCA-associated ovarian cancer: from molecular genetics to risk management.
AB - Ovarian cancer (OC) mostly arises sporadically, but a fraction of cases are
associated with mutations in BRCA1 and BRCA2 genes. The presence of a BRCA
mutation in OC patients has been suggested as a prognostic and predictive factor.
In addition, the identification of asymptomatic carriers of such mutations offers
an unprecedented opportunity for OC prevention. This review is aimed at exploring
the current knowledge on epidemiological and molecular aspects of BRCA-associated
OC predisposition, on pathology and clinical behavior of OC occurring in BRCA
mutation carriers, and on the available options for managing asymptomatic
carriers.
PMID- 25136626
TI - Fermentative polyhydroxybutyrate production from a novel feedstock derived from
bakery waste.
AB - In this study, Halomonas boliviensis was cultivated on bakery waste hydrolysate
and seawater in batch and fed-batch cultures for polyhydroxybutyrate (PHB)
production. Results demonstrated that bakery waste hydrolysate and seawater could
be efficiently utilized by Halomonas boliviensis while PHB contents between 10
and 30% (w/w) were obtained. Furthermore, three methods for bakery waste
hydrolysis were investigated for feedstock preparation. These include: (1) use of
crude enzyme extracts from Aspergillus awamori, (2) Aspergillus awamori solid
mashes, and (3) commercial glucoamylase. In the first method, the resultant free
amino nitrogen (FAN) concentration in hydrolysates was 150 and 250 mg L(-1) after
20 hours at enzyme-to-solid ratios of 6.9 and 13.1 U g(-1), respectively. In both
cases, the final glucose concentration was around 130-150 g L(-1). In the second
method, the resultant FAN and glucose concentrations were 250 mg L(-1) and 150 g
L(-1), respectively. In the third method, highest glucose and lowest FAN
concentrations of 170-200 g L(-1) and 100 mg L(-1), respectively, were obtained
in hydrolysates after only 5 hours. The present work has generated promising
information contributing to the sustainable production of bioplastic using bakery
waste hydrolysate.
PMID- 25136627
TI - Abarema cochliacarpos extract decreases the inflammatory process and skeletal
muscle injury induced by Bothrops leucurus venom.
AB - Snakebites are a public health problem, especially in tropical countries.
However, treatment with antivenom has limited effectiveness against venoms' local
effects. Here, we investigated the ability of Abarema cochliacarpos
hydroethanolic extract (EAc) to protect mice against injection of Bothrops
leucurus venom. Swiss mice received perimuscular venom injection and were
subsequently treated orally with EAc in different doses. Treatment with EAc 100,
200, and 400 mg/kg reduced the edema induced by B. leucurus in 1%, 13%, and 39%,
respectively. Although lower doses showed no antihypernociceptive effect in the
Von Frey test, the higher dose significantly reduced hyperalgesia induced by the
venom. Antimyotoxic activity of EAc was also observed by microscopy assessment,
with treated muscles presenting preserved structures, decreased edema, and
inflammatory infiltrate as compared to untreated ones. Finally, on the rotarod
test, the treated mice showed better motor function, once muscle fibers were
preserved and there were less edema and pain. Treated mice could stand four times
more time on the rotating rod than untreated ones. Our results have shown that
EAc presented relevant activities against injection of B. leucurus venom in mice,
suggesting that it can be considered as an adjuvant in the treatment of
envenomation.
PMID- 25136629
TI - Hot-stage microscopy for determination of API particles in a formulated tablet.
AB - Although methods exist to readily determine the particle size distribution (PSD)
of an active pharmaceutical ingredient (API) before its formulation into a final
product, the primary challenge is to develop a method to determine the PSD of
APIs in a finished tablet. To address the limitations of existing PSD methods, we
used hot-stage microscopy to observe tablet disintegration during temperature
change and, thus, reveal the API particles in a tablet. Both mechanical and
liquid disintegration were evaluated after we had identified optimum milling time
for mechanical disintegration and optimum volume of water for liquid
disintegration. In each case, hot-stage micrographs, taken before and after the
API melting point, were compared with image analysis software to obtain the PSDs.
Then, the PSDs of the APIs from the disintegrated tablets were compared with the
PSDs of raw APIs. Good agreement was obtained, thereby confirming the robustness
of our methodology. The availability of such a method equips pharmaceutical
scientists with an in vitro assessment method that will more reliably determine
the PSD of active substances in finished tablets.
PMID- 25136628
TI - Evaluation of the efficacy of 50% autologous serum eye drops in different ocular
surface pathologies.
AB - PURPOSE: This study evaluated the efficacy of 50% autologous serum eye drops in
ocular surface diseases not improved by conventional therapy. METHODS: We
analyzed two groups: (1) acute eye pathologies (e.g., chemical burns) and (2)
chronic eye pathologies (e.g., recurrent corneal erosion, neurotropic keratitis,
and keratoconjunctivitis sicca). The patients were treated for surface
instability after conventional therapy. The patients received therapy 5 times a
day until stabilization of the framework; they then reduced therapy to 3 times a
day for at least 3 months. We analyzed the best corrected visual acuity,
epithelial defects, inflammation, corneal opacity, and corneal
neovascularization. We also analyzed symptoms such as tearing, burning, sense of
foreign body or sand, photophobia, blurred vision, and difficulty opening the
eyelids. RESULTS: We enrolled 15 eyes in group 1 and 11 eyes in group 2. The
average therapy period was 16 +/- 5.86 weeks in group 1 and 30.54 +/- 20.33 weeks
in group 2. The epithelial defects all resolved. Signs and symptoms improved in
both groups. In group 2, the defect recurred after the suspension of therapy in 2
(18%) patients; in group 1, no defects recurred. CONCLUSIONS: Autologous serum
eye drops effectively stabilize and improve signs and symptoms in eyes previously
treated with conventional therapy.
PMID- 25136631
TI - Large-scale genomic analysis of codon usage in dengue virus and evaluation of its
phylogenetic dependence.
AB - The increasing number of dengue virus (DENV) genome sequences available allows
identifying the contributing factors to DENV evolution. In the present study, the
codon usage in serotypes 1-4 (DENV1-4) has been explored for 3047 sequenced
genomes using different statistics methods. The correlation analysis of total GC
content (GC) with GC content at the three nucleotide positions of codons (GC1,
GC2, and GC3) as well as the effective number of codons (ENC, ENCp) versus GC3
plots revealed mutational bias and purifying selection pressures as the major
forces influencing the codon usage, but with distinct pressure on specific
nucleotide position in the codon. The correspondence analysis (CA) and clustering
analysis on relative synonymous codon usage (RSCU) within each serotype showed
similar clustering patterns to the phylogenetic analysis of nucleotide sequences
for DENV1-4. These clustering patterns are strongly related to the virus
geographic origin. The phylogenetic dependence analysis also suggests that
stabilizing selection acts on the codon usage bias. Our analysis of a large scale
reveals new feature on DENV genomic evolution.
PMID- 25136632
TI - Anatomic changes in the macroscopic morphology and microarchitecture of
denervated long bone tissue after spinal cord injury in rats.
AB - To study the effects of mechanical loading on bones after SCI, we assessed macro-
and microscopic anatomy in rats submitted to passive standing (PS) and electrical
stimulation (ES). The study design was based on two main groups of juvenile male
Wistar rats with SCI: one was followed for 33 days with therapies starting at day
3 and the other was followed for 63 days with therapies starting at day 33. Both
groups were composed of four subgroups (n = 10/group): (1) Sham, (2) SCI, (3) SCI
+ PS, and (4) SCI + ES. Rehabilitation protocol consisted of a 20-minute session,
3x/wk for 30 days. The animals were sequentially weighed and euthanized. The
femur and tibia were assessed macroscopically and microscopically by scanning
electronic microscopy (SEM). The SCI rats gained less weight than Sham-operated
animals. Significant reduction of bone mass and periosteal radii was observed in
the SCI rats, whereas PS and ES efficiently improved the macroscopic parameters.
The SEM images showed less and thin trabecular bone in SCI rats. PS and ES
efficiently ameliorated the bone microarchitecture deterioration by thickening
and increasing the trabeculae. Based on the detrimental changes in bone tissue
following SCI, the mechanical loading through weight bearing and muscle
contraction may decrease the bone loss and restore the macro- and microanatomy.
PMID- 25136630
TI - Potential therapeutic strategies for Alzheimer's disease targeting or beyond beta
amyloid: insights from clinical trials.
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder with two
hallmarks: beta-amyloid plagues and neurofibrillary tangles. It is one of the
most alarming illnesses to elderly people. No effective drugs and therapies have
been developed, while mechanism-based explorations of therapeutic approaches have
been intensively investigated. Outcomes of clinical trials suggested several
pitfalls in the choice of biomarkers, development of drug candidates, and
interaction of drug-targeted molecules; however, they also aroused concerns on
the potential deficiency in our understanding of pathogenesis of AD, and
ultimately stimulated the advent of novel drug targets tests. The anticipated
increase of AD patients in next few decades makes development of better therapy
an urgent issue. Here we attempt to summarize and compare putative therapeutic
strategies that have completed clinical trials or are currently being tested from
various perspectives to provide insights for treatments of Alzheimer's disease.
PMID- 25136633
TI - Acute in vivo response to an alternative implant for urogynecology.
AB - PURPOSE: To investigate in vivo the acute host response to an alternative implant
designed for the treatment of stress urinary incontinence (SUI) and pelvic organ
prolapse (POP). METHODS: A biodegradable scaffold was produced from poly-L-lactic
acid (PLA) using the electrospinning technique. Human and rat adipose-derived
stem cells (ADSCs) were isolated and characterized by fluorescence-activated cell
sorting and differentiation assays. PLA scaffolds were seeded and cultured for 2
weeks with human or rat ADSCs. Scaffolds with and without human or rat ADSCs were
implanted subcutaneously on the abdominal wall of rats. After 3 and 7 days, 6
animals from each group were sacrificed. Sections from each sample were analyzed
by Haematoxylin and Eosin staining, Sirius red staining, and immunohistochemistry
for CD68, PECAM-1, and collagen I and III. RESULTS: Animals responded to the
scaffolds with an acute macrophage response. After 7 days of implantation, there
was extensive host cell penetration, new blood vessel formation, and new collagen
deposition throughout the full thickness of the samples without obvious
differences between cell-containing and cell-free scaffolds. CONCLUSIONS: The
acute in vivo response to an alternative implant (both with and without cells)
for the treatment of SUI and POP showed good acute integration into the host
tissues.
PMID- 25136635
TI - Pathological feature and immunoprofile of cystitis glandularis accompanied with
upper urinary tract obstruction.
AB - OBJECTIVE: To explore the pathological feature and immunoprofile of immunoprofile
accompanied with upper urinary tract obstruction and the immunoprofile in various
types of glandular cystitis. METHODS: Pathological sections from 31 cases of
cystitis glandularis with upper urinary tract obstruction and 34 cases of
cystitis glandularis without upper urinary tract obstruction were observed as
pathological feature on microscopy. Meanwhile, an immunohistochemical analysis
was employed to determine the expression of p53, Ki67, p21, MMP-9, MUC1, MUC2,
and COX-2. RESULTS: In the two groups, main pathological type was transitional
epithelial, followed by intestinal epithelial; other types were a few, and the
difference between the two groups was not significant. All immunohistochemical
expressions of p53, Ki67, p21, MMP-9, MUC1, MUC2, and COX-2 were positive in
varying degrees, and there was no significant difference between the groups.
Transitional epithelial type was compared with mixed type; the difference of COX
2 was significant, P < 0.05. The differences of immunohistochemical expression
among other different pathologic types were not significant. CONCLUSIONS: It is
suggested that glandular cystitis accompanied with upper urinary tract
obstruction shares the same pathological feature and immunoprofile as that
without upper urinary tract obstruction. No significant differences of
immunohistochemical expression in tissue are in cystitis glandularis with
different pathological types.
PMID- 25136636
TI - Potential smoothened inhibitor from traditional Chinese medicine against the
disease of diabetes, obesity, and cancer.
AB - Nowadays, obesity becomes a serious global problem, which can induce a series of
diseases such as type 2 diabetes mellitus, cancer, cardiovascular disease,
metabolic syndrome, and stoke. For the mechanisms of diseases, the hedgehog
signaling pathway plays an important role in body patterning during
embryogenesis. For this reason, smoothened homologue (Smo) protein had been
indicated as the drug target. In addition, the small-molecule Smo inhibitor had
also been used in oncology clinical trials. To improve drug development of TCM
compounds, we aim to investigate the potent lead compounds as Smo inhibitor from
the TCM compounds in TCM Database@Taiwan. The top three TCM compounds,
precatorine, labiatic acid, and 2,2'-[benzene-1,4-diylbis(methanediyloxybenzene
4,1-diyl)]bis(oxoacetic acid), have displayed higher potent binding affinities
than the positive control, LY2940680, in the docking simulation. After MD
simulations, which can optimize the result of docking simulation and validate the
stability of H-bonds between each ligand and Smo protein under dynamic
conditions, top three TCM compounds maintain most of interactions with Smo
protein, which keep the ligand binding stable in the binding domain. Hence, we
propose precatorine, labiatic acid, and 2,2'-[benzene-1,4
diylbis(methanediyloxybenzene-4,1-diyl)]bis(oxoacetic acid) as potential lead
compounds for further study in drug development process with the Smo protein.
PMID- 25136637
TI - Dracocephalum: novel anticancer plant acting on liver cancer cell mitochondria.
AB - Dracocephalum kotschyi Boiss. (Labiatae) is a native Iranian medicinal plant
which has been used in combination with Peganum harmala L. as a remedy for many
forms of human cancer especially leukemia and gastrointestinal malignancies.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death
worldwide. In this investigation HCC was induced by a single intraperitoneal
injection of diethylnitrosamine (DEN) in corn oil at 200 mg/kg body weight to
rats. Two weeks after DEN administration, cancer development was promoted with
dietary 2-acetylaminofluorene (2-AAF) (0.02%, w/w) for 2 weeks. Serum alpha
fetoprotein (AFP) concentration, serum alanine transaminase (ALT), aspartate
transaminase (AST), and alkaline phosphatase (ALP) activities were also
determined for confirmation of hepatocellular carcinoma induction. Then rat
hepatocytes were isolated with collagen perfusion technique and tumoral
hepatocytes were sorted by flow cytometry. Finally isolated mitochondria obtained
from both tumoral and nontumoral hepatocytes were used for any probable toxic
effect of Dracocephalum kotschyi ethanolic extract. Our results showed that D.
kotschyi extract (250 ug/mL) induced reactive oxygen species (ROS) formation,
mitochondrial membrane permeabilization (MMP), and mitochondrial swelling and
cytochrome c release only in tumoral but not nontumoral hepatocyte. These
findings propose Dracocephalum kotschyi as a promising candidate for future
anticancer research.
PMID- 25136638
TI - The effects of vitamin E and omega-3 PUFAs on endothelial function among
adolescents with metabolic syndrome.
AB - AIM: The present study aims to explore the effects of vitamin E and omega-3 on
endothelial function indicators among adolescents with metabolic syndrome.
METHOD: In a randomized, double blind, and placebo-controlled trial, 90 young
individuals, aged 10 to 18 years, with metabolic syndrome were randomly assigned
to receive either vitamin E tablets (400 IU/day) or omega-3 tablets (2.4 gr/day)
or placebo. For assessing endothelial functional state, the serum level of
vascular endothelial growth factor (VEGF) was measured by ELISA test. RESULTS:
The use of omega-3 supplementation for eight weeks led to significant increase in
serum HDL level compared with the group treated with vitamin E or placebo group.
In this regard, no significant correlations were found between the change in VEGF
and baseline levels of other markers including anthropometric indices and serum
lipids. Omega-3 could significantly reduce VEGF with the presence of other
baseline variables (Beta = -12.55; P = 0.012). CONCLUSION: The administration of
omega-3 can effectively improve endothelial function in adolescents with
metabolic syndrome by reducing the level of serum VEGF, as a major index for
atherosclerosis progression and endothelial destabilization. Omega-3 can be
proposed as a VEGF antagonist for improving endothelial function in metabolic
syndrome. The clinical implications of our findings should be assessed in future
studies.
PMID- 25136639
TI - Magnetic resonance imaging for the normal mesostenium and involvement of the
mesostenium in acute pancreatitis.
AB - The main point of this paper is to study MRI findings of the normal mesostenium
and the involvement of the mesostenium in acute pancreatitis and to discuss the
relationship between the involvement of the mesostenium and the severity of acute
pancreatitis. In clinical practice, the mesenterical involvement in acute
pancreatitis was often observed on MRI in daily works, which was little recorded
in the reported studies. We conducted the current study to assess the
mesenterical involvement in acute pancreatitis with MRI. We found that the
mesenterical involvement of acute pancreatitis patients is common on MRI. The
mesenterical involvement has a positive correlation with the MR severity index
and the Acute Physiology and Chronic Healthy Evaluation II scoring system. It has
been shown that MR can be used to visualize mesenterical involvement, which is a
supplementary indicator in evaluating the severity of acute pancreatitis and
local and systemic complications.
PMID- 25136634
TI - Drug delivery systems, CNS protection, and the blood brain barrier.
AB - Present review highlights various drug delivery systems used for delivery of
pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides,
and other therapeutic substances through the endothelial capillaries (BBB) for
CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic
agents/biomolecules such as proline rich peptides, prodrugs,
radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the
target sites in deep tissue locations inside tumor sites of brain has been
explained. In addition, therapeutic applications of various types of
nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes,
niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid
nanoparticles, colloidal drug carriers, liposomes, and micelles have been
discussed with their recent advancements. Emphasis has been given on the need of
physiological and therapeutic optimization of existing drug delivery methods and
their carriers to deliver therapeutic amount of drug into the brain for treatment
of various neurological diseases and disorders. Further, strong recommendations
are being made to develop nanosized drug carriers/vehicles and noninvasive
therapeutic alternatives of conventional methods for better therapeutics of CNS
related diseases. Hence, there is an urgent need to design nontoxic biocompatible
drugs and develop noninvasive delivery methods to check posttreatment clinical
fatalities in neuropatients which occur due to existing highly toxic invasive
drugs and treatment methods.
PMID- 25136640
TI - Murine aortic smooth muscle cells acquire, though fail to present exogenous
protein antigens on major histocompatibility complex class II molecules.
AB - In the present study aortic murine smooth muscle cell (SMC) antigen presentation
capacity was evaluated using the Ealpha-GFP/Y-Ae system to visualize antigen
uptake through a GFP tag and tracking of Ealpha peptide/MHCII presentation using
the Y-Ae Ab. Stimulation with IFN-gamma (100 ng/mL) for 72 h caused a significant
(P < 0.01) increase in the percentage of MHC class II positive SMCs, compared
with unstimulated cells. Treatment with Ealpha-GFP (100 MUg/mL) for 48 h induced
a significant (P < 0.05) increase in the percentage of GFP positive SMCs while it
did not affect the percentage of Y-Ae positive cells, being indicative of antigen
uptake without its presentation in the context of MHC class II. After IFN-gamma
stimulation, ovalbumin- (OVA, 1 mg/mL) or OVA323-339 peptide-(0.5 MUg/mL) treated
SMCs failed to induce OT-II CD4(+) T cell activation/proliferation; this was also
accompanied by a lack of expression of key costimulatory molecules (OX40L, CD40,
CD70, and CD86) on SMCs. Finally, OVA-treated SMCs failed to induce DO11.10-GFP
hybridoma activation, a process independent of costimulation. Our results
demonstrate that while murine primary aortic SMCs express MHC class II and can
acquire exogenous antigens, they fail to activate T cells through a failure in
antigen presentation and a lack of costimulatory molecule expression.
PMID- 25136642
TI - Diabetic retinopathy treated with laser photocoagulation and the indirect effect
on glycaemic control.
AB - PURPOSE: To identify any possible relation between glycaemic control and previous
laser photocoagulation for diabetic retinopathy. METHODS: Seventy-two patients
with diabetes were included in the study and were separated into 2 groups
according to previous treatment (group A) or not (group B) with argon laser
photocoagulation. Glycaemic control was estimated by measuring blood levels of
HbA1c in four consecutive measurements. RESULTS: Blood levels of HbA1c in group A
were significantly lower 3, 6, and 12 months after laser treatment as compared to
blood levels of HbA1c before laser treatment (7.1 +/- 0.4% versus 7.6 +/- 0.9%,
7.2 +/- 0.2% versus 7.6 +/- 0.9%, and 7.1 +/- 0.2% versus 7.6 +/- 0.9%, resp.,
all P < 0.05). Blood levels of HbA1c in group B did not differ significantly in
four consecutive measurements. CONCLUSION: Our results suggest that we should
anticipate a better glycaemic control in cases of patients with diabetes
previously treated with laser photocoagulation.
PMID- 25136641
TI - Protein kinase D3 is essential for prostratin-activated transcription of
integrated HIV-1 provirus promoter via NF-kappaB signaling pathway.
AB - Prostratin has been proposed as a promising reagent for eradicating the latent
HIV-1 provirus by inducing HIV-1 transcription activation. The molecular
mechanism of this activation, however, is far from clear. Here, we show that the
protein kinase D3 (PKD3) is essential for prostratin-induced transcription
activation of latent HIV-1 provirus. First, silencing PKD3, but not the other
members of PKD family, blocked prostratin-induced transcription of HIV-1. Second,
overexpressing the constitutively active form of PKD3, but not the wild-type or
kinase-dead form of PKD3, augmented the expression of HIV-1. Consistent with this
observation, we found that prostratin could trigger PKD3 activation by inducing
the phosphorylation of its activation loop. In addition, we identified PKCepsilon
of the novel PKC subfamily as the upstream kinase for this phosphorylation.
Finally, the activation effect of PKD3 on HIV-1 transcription was shown to depend
on the presence of kappaB element and the prostratin-induced activation of NF
kappaB, as indicated by the fact that silencing PKD3 blocked prostratin-induced
NF-kappaB activation and NF-kappaB-dependent HIV-1 transcription. Therefore, for
the first time, PKD3 is implicated in the transcription activation of latent HIV
1 provirus, and our results revealed a molecular mechanism of prostratin-induced
HIV-1 transcription via PKCepsilon/PKD3/NF-kappaB signaling pathway.
PMID- 25136643
TI - Real life cancer comorbidity in Greek patients with diabetes mellitus followed up
at a single diabetes center: an unappreciated new diabetes complication.
AB - We determined cancer comorbidity in patients with diabetes followed up at a
single Greek academic clinic and investigated the potential related factors.
Cancer comorbidity was prospectively recorded for all patients with type 2 (T2DM,
n = 759) or type 1 (T1DM, n = 134) diabetes of at least 10-year duration examined
during one year. Patient characteristics, diabetes age of onset, duration,
treatment, control, and complication rates were compared between subjects with
and without cancer. Moreover, a retrospective collection of data from similar
patients examined for the first time during the last 25 years, but lost to follow
up, after at least one-year's regular visits, was performed. In regularly
followed-up T2DM patients cancer comorbidity was 12.6%. Patients with cancer were
older and more frequently smokers. Prostate cancer was the most frequent (24.0%)
type. In T1DM cancer comorbidity was 3.0%. Similar rates of comorbidity and types
of cancer were observed in lost to follow-up patients. In conclusion, our
patients with T2DM of at least 10-year' duration show high cancer comorbidity. No
specific characteristics discriminate patients with cancer. Therefore
presymptomatic cancer detection and prevention strategies may have to be
incorporated into the annual systematic evaluation of our patients.
PMID- 25136644
TI - Rectal sensitivity in diabetes patients with symptoms of gastroparesis.
AB - In a clinical setting, diabetic autonomic complications (cardiac,
gastrointestinal, urogenital, etc.) are often handled as separate entities. We
investigated rectal sensitivity to heat, mechanical distension, and electrical
stimulations in 20 patients with diabetes and symptoms of gastroparesis, to
evaluate the extent of visceral neuronal damage. Furthermore, to evaluate the
relation between the nervous structures we examined gastric emptying and cardiac
autonomic function with the hypothesis being an association between these. We
found that 60% of patients had delayed gastric empting. Rectal hyposensitivity
was a general finding as they tolerated 67% higher thermal, 42% more mechanical,
and 33% higher electrical current intensity compared to healthy controls. In
patients, most heart rate variability parameters were reduced; they reported
significantly more gastrointestinal symptoms and a reduced quality of life in all
SF-36 domains. Shortened RR interval correlated with reduced rectal temperature
sensitivity, and gastric retention rate was negatively associated with symptoms
of nausea and vomiting. To conclude, in these patients with signs and symptoms of
diabetic gastroparesis, rectal sensitivity was reduced, and heart rate
variability was impaired. Thus, we suggest regarding diabetic autonomic
neuropathy as a diffuse disorder. Symptoms of widespread autonomic dysfunction
and sensory disorders should be expected and treated in these patients.
PMID- 25136645
TI - The effect of diabetes self-management education on body weight, glycemic
control, and other metabolic markers in patients with type 2 diabetes mellitus.
AB - AIMS: To comprehensively evaluate the effect of a short-term diabetes self
management education (DSME) on metabolic markers and atherosclerotic parameters
in patients with type 2 diabetes. METHODS: 76 patients with type 2 diabetes were
recruited in this study. They were divided into the intervention group (n = 36)
and control group (n = 40). The patients in the intervention group received a 3
month intervention, including an 8-week education on self-management of diabetes
mellitus and subsequent 4 weeks of practice of the self-management guidelines.
The patients in the control group received standard advice on medical nutrition
therapy. Metabolic markers, carotid intima-media thickness (CIMT), and carotid
arterial stiffness (CAS) of the patients in both groups were assessed before and
after the 3-month intervention. RESULTS: There was a significant reduction in
hemoglobin A1c (HbA1c, -0.2 +/- 0.56% versus 0.08 +/- 0.741%; P < 0.05) and body
weight (-1.19 +/- 1.39 kg versus -0.61 +/- 2.04 kg; P < 0.05) in the intervention
group as compared to the control group. However, no significant improvements were
found in other metabolic markers, CIMT and CAS (P > 0.05). CONCLUSIONS: DSME can
improve HbA1c and body weight in patients with type 2 diabetes.
PMID- 25136647
TI - Pollution characteristics and possible sources of seldom monitored trace elements
in surface sediments collected from Three Gorges Reservoir, China.
AB - A geochemical study of Three Gorges Reservoir (TGR) sediments was carried out to
analyze the concentrations, distribution, accumulation, and potential sources of
the seldom monitored trace elements (SMTEs). The mean concentrations of Li, B,
Be, Bi, V, Co, Ga, Sn, Sb, and Tl were 47.08, 2.47, 59.15, 0.50, 119.20, 17.83,
30.31, 3.25, 4.14, and 0.58 mg/kg, respectively. The concentrations of total
SMTEs, together with their spatial distribution, showed that the SMTEs were
mainly due to anthropogenic inputs in the region of TGR. The assessment by
Geoaccumulation Index indicates that Tl, Be, V, Co, and Fe are at the unpolluted
level; Bi, Li, Ga, and Sn were at the "uncontaminated to moderately contaminated"
level. However, B was classified as "moderately contaminated" level and Sb was
ranked as "strongly contaminated" level. The pollution level of the SMTEs is Sb >
B > Bi > Li > Ga > Sn > Tl > Be > V > Co > Fe. The results of Correlation
Analysis and Principal Component Analysis indicated Be, V, Co, Ga, Sn, Tl, Bi,
and Fe in sediments have a natural source. B and Li were positively correlated
with each other and mainly attributed into similar anthropogenic input. In
addition, Sb has less relationship with other SMTEs, indicating that Sb has
another kind of anthropogenic source.
PMID- 25136646
TI - Effects of pristane alone or combined with chloroquine on macrophage activation,
oxidative stress, and TH1/TH2 skewness.
AB - We investigated the protective role of chloroquine against pristane-induced
macrophage activation, oxidative stress, and Th1/Th2 skewness in C57BL/6J mice.
Those mice were treated with pristane alone or combined with chloroquine.
Hematological and biochemical parameters, macrophage phagocytic function, the
oxidant/antioxidant index, cytokine for IFN-gamma, TNF-alpha, IL-4, and IL-6, and
the isotypes of IgG2a and IgG1 were determined. And the expression of T-bet/GATA
3 and IL-12/IL-10 mRNA in spleen were analyzed by real-time PCR. We found that
pristane treatment for a period of 12 or 24 weeks triggered macrophage activation
syndrome, characterized by hemophagocytosis in spleen and peripheral blood,
enhanced lipid phagocytosis by peritoneal macrophages in vitro, erythropenia and
leucopenia, increased anti-Smith, lactic dehydrogenase, triglyceride, and
ferritin, as well as hypercytokinemia of IFN-gamma, TNF-alpha, IL-4, and IL-6. In
parallel, a significant increase in lipid peroxidation and a decrease in
superoxide dismutase, glutathione, and catalase activity, as well as a skewed
Th1/Th2 balance in spleen, were observed. However, chloroquine supplementation
showed a remarkable amelioration of these abnormalities. Our data indicate that
pristane administration induces macrophage activation, oxidative stress, and
Th1/Th2 skewness, which can be attenuated by chloroquine.
PMID- 25136648
TI - Low-cost dielectric substrate for designing low profile multiband monopole
microstrip antenna.
AB - This paper proposes a small sized, low-cost multiband monopole antenna which can
cover the WiMAX bands and C-band. The proposed antenna of 20 * 20 mm(2) radiating
patch is printed on cost effective 1.6 mm thick fiberglass polymer resin
dielectric material substrate and fed by 4 mm long microstrip line. The finite
element method based, full wave electromagnetic simulator HFSS is efficiently
utilized for designing and analyzing the proposed antenna and the antenna
parameters are measured in a standard far-field anechoic chamber. The
experimental results show that the prototype of the antenna has achieved
operating bandwidths (voltage stand wave ratio (VSWR) less than 2) 360 MHz (2.53
2.89 GHz) and 440 MHz (3.47-3.91 GHz) for WiMAX and 1550 MHz (6.28-7.83 GHz) for
C-band. The simulated and measured results for VSWR, radiation patterns, and gain
are well matched. Nearly omnidirectional radiation patterns are achieved and the
peak gains are of 3.62 dBi, 3.67 dBi, and 5.7 dBi at 2.66 GHz, 3.65 GHz, and 6.58
GHz, respectively.
PMID- 25136649
TI - A routing path construction method for key dissemination messages in sensor
networks.
AB - Authentication is an important security mechanism for detecting forged messages
in a sensor network. Each cluster head (CH) in dynamic key distribution schemes
forwards a key dissemination message that contains encrypted authentication keys
within its cluster to next-hop nodes for the purpose of authentication. The
forwarding path of the key dissemination message strongly affects the number of
nodes to which the authentication keys in the message are actually distributed.
We propose a routing method for the key dissemination messages to increase the
number of nodes that obtain the authentication keys. In the proposed method, each
node selects next-hop nodes to which the key dissemination message will be
forwarded based on secret key indexes, the distance to the sink node, and the
energy consumption of its neighbor nodes. The experimental results show that the
proposed method can increase by 50-70% the number of nodes to which
authentication keys in each cluster are distributed compared to geographic and
energy-aware routing (GEAR). In addition, the proposed method can detect false
reports earlier by using the distributed authentication keys, and it consumes
less energy than GEAR when the false traffic ratio (FTR) is >= 10%.
PMID- 25136650
TI - Graph-based symbolic technique and its application in the frequency response
bound analysis of analog integrated circuits.
AB - A new graph-based symbolic technique (GBST) for deriving exact analytical
expressions like the transfer function H(s) of an analog integrated circuit (IC),
is introduced herein. The derived H(s) of a given analog IC is used to compute
the frequency response bounds (maximum and minimum) associated to the magnitude
and phase of H(s), subject to some ranges of process variational parameters, and
by performing nonlinear constrained optimization. Our simulations demonstrate the
usefulness of the new GBST for deriving the exact symbolic expression for H(s),
and the last section highlights the good agreement between the frequency response
bounds computed by our variational analysis approach versus traditional Monte
Carlo simulations. As a conclusion, performing variational analysis using our
proposed GBST for computing the frequency response bounds of analog ICs, shows a
gain in computing time of 100x for a differential circuit topology and 50x for a
3-stage amplifier, compared to traditional Monte Carlo simulations.
PMID- 25136651
TI - An action-based fine-grained access control mechanism for structured documents
and its application.
AB - This paper presents an action-based fine-grained access control mechanism for
structured documents. Firstly, we define a describing model for structured
documents and analyze the application scenarios. The describing model could
support the permission management on chapters, pages, sections, words, and
pictures of structured documents. Secondly, based on the action-based access
control (ABAC) model, we propose a fine-grained control protocol for structured
documents by introducing temporal state and environmental state. The protocol
covering different stages from document creation, to permission specification and
usage control are given by using the Z-notation. Finally, we give the
implementation of our mechanism and make the comparisons between the existing
methods and our mechanism. The result shows that our mechanism could provide the
better solution of fine-grained access control for structured documents in
complicated networks. Moreover, it is more flexible and practical.
PMID- 25136652
TI - Determination of the sediment carrying capacity based on perturbed theory.
AB - According to the previous studies of sediment carrying capacity, a new method of
sediment carrying capacity on perturbed theory was proposed. By taking into
account the average water depth, average flow velocity, settling velocity, and
other influencing factors and introducing the median grain size as one main
influencing factor in deriving the new formula, we established a new sediment
carrying capacity formula. The coefficients were determined by the principle of
dimensional analysis, multiple linear regression method, and the least square
method. After that, the new formula was verified through measuring data of
natural rivers and flume tests and comparing the verified results calculated by
Cao Formula, Zhang Formula, Li Formula, Engelung-Hansen Formula, Ackers-White
Formula, and Yang Formula. According to the compared results, it can be seen that
the new method is of high accuracy. It could be a useful reference for the
determination of sediment carrying capacity.
PMID- 25136653
TI - Multivariable time series prediction for the icing process on overhead power
transmission line.
AB - The design of monitoring and predictive alarm systems is necessary for successful
overhead power transmission line icing. Given the characteristics of complexity,
nonlinearity, and fitfulness in the line icing process, a model based on a
multivariable time series is presented here to predict the icing load of a
transmission line. In this model, the time effects of micrometeorology parameters
for the icing process have been analyzed. The phase-space reconstruction theory
and machine learning method were then applied to establish the prediction model,
which fully utilized the history of multivariable time series data in local
monitoring systems to represent the mapping relationship between icing load and
micrometeorology factors. Relevant to the characteristic of fitfulness in line
icing, the simulations were carried out during the same icing process or
different process to test the model's prediction precision and robustness.
According to the simulation results for the Tao-Luo-Xiong Transmission Line, this
model demonstrates a good accuracy of prediction in different process, if the
prediction length is less than two hours, and would be helpful for power grid
departments when deciding to take action in advance to address potential icing
disasters.
PMID- 25136654
TI - Inducing effect of dihydroartemisinic acid in the biosynthesis of artemisinins
with cultured cells of Artemisia annua by enhancing the expression of genes.
AB - Artemisinin has been used in the production of "artemisinin combination
therapies" for the treatment of malaria. Feeding of precursors has been proven to
be one of the most effective methods to enhance artemisinin production in plant
cultured cells. At the current paper, the biosynthesis of artemisinin (ART) and
its four analogs from dihydroartemisinic acid (DHAA) in suspension-cultured cells
of Artemisia annua were investigated. ARTs were detected by HPLC/GC-MS and
isolated by various chromatography methods. The structures of four DHAA
metabolites, namely, dihydro-epi-deoxyarteannuin B, arteannuin I, arteannuin K,
and 3-beta-hydroxy-dihydro-epi-deoxyarteannuin B, were elucidated by
physicochemical and spectroscopic analyses. The correlation between gene
expression and ART content was investigated. The results of RT-PCR showed that
DHAA could up-regulate expression of amorpha-4,11-diene synthase gene (ADS),
amorpha-4,11-diene C-12 oxidase gene (CYP71AV1), and farnesyl diphosphate
synthase gene (FPS) (3.19-, 7.21-, and 2.04-fold higher than those of control
group, resp.), which indicated that biosynthesis processes from DHAA to ART were
enzyme-mediated.
PMID- 25136655
TI - Automatic foreground extraction based on difference of Gaussian.
AB - A novel algorithm for automatic foreground extraction based on difference of
Gaussian (DoG) is presented. In our algorithm, DoG is employed to find the
candidate keypoints of an input image in different color layers. Then, a
keypoints filter algorithm is proposed to get the keypoints by removing the
pseudo-keypoints and rebuilding the important keypoints. Finally, Normalized cut
(Ncut) is used to segment an image into several regions and locate the foreground
with the number of keypoints in each region. Experiments on the given image data
set demonstrate the effectiveness of our algorithm.
PMID- 25136656
TI - Comprehensive Aspectual UML approach to support AspectJ.
AB - Unified Modeling Language is the most popular and widely used Object-Oriented
modelling language in the IT industry. This study focuses on investigating the
ability to expand UML to some extent to model crosscutting concerns (Aspects) to
support AspectJ. Through a comprehensive literature review, we identify and
extensively examine all the available Aspect-Oriented UML modelling approaches
and find that the existing Aspect-Oriented Design Modelling approaches using UML
cannot be considered to provide a framework for a comprehensive Aspectual UML
modelling approach and also that there is a lack of adequate Aspect-Oriented tool
support. This study also proposes a set of Aspectual UML semantic rules and
attempts to generate AspectJ pseudocode from UML diagrams. The proposed Aspectual
UML modelling approach is formally evaluated using a focus group to test six
hypotheses regarding performance; a "good design" criteria-based evaluation to
assess the quality of the design; and an AspectJ-based evaluation as a reference
measurement-based evaluation. The results of the focus group evaluation confirm
all the hypotheses put forward regarding the proposed approach. The proposed
approach provides a comprehensive set of Aspectual UML structural and behavioral
diagrams, which are designed and implemented based on a comprehensive and
detailed set of AspectJ programming constructs.
PMID- 25136657
TI - Radixin enhances colon cancer cell invasion by increasing MMP-7 production via
Rac1-ERK pathway.
AB - As a member of the ezrin-radixin-moesin (ERM) family, radixin is overexpressed in
many tumor tissues. However, little is known about its role in the progression of
colon cancer. So we here aimed to determine the function of radixin in colon
cancer cell invasion. Interestingly, we found that the expression of radixin was
significantly elevated in colon cancer cells. Knockdown of radixin suppressed the
invasion and migration of colon cancer cells. Further, knockdown of radixin
inhibited the activation of Rac1 and ERK1/2, and decreased the expression and
secretion of MMP-7. In addition, Rac1-ERK signaling pathway was required for the
radixin-promoted invasion and MMP-7 production. Together, our findings suggest
that radixin enhances the invasion and migration of colon cancer cells.
Activation of Rac1-ERK pathway and consequent upregulation of MMP-7 production
may contribute to the function of radixin in the regulation of colon cancer cell
invasion. Thus, radixin may act as a novel target for the diagnosis and treatment
of colon cancer.
PMID- 25136659
TI - Advanced approach to information security management system model for industrial
control system.
AB - Organizations make use of important information in day-to-day business.
Protecting sensitive information is imperative and must be managed. Companies in
many parts of the world protect sensitive information using the international
standard known as the information security management system (ISMS). ISO 27000
series is the international standard ISMS used to protect confidentiality,
integrity, and availability of sensitive information. While an ISMS based on ISO
27000 series has no particular flaws for general information systems, it is unfit
to manage sensitive information for industrial control systems (ICSs) because the
first priority of industrial control is safety of the system. Therefore, a new
information security management system based on confidentiality, integrity, and
availability as well as safety is required for ICSs. This new ISMS must be
mutually exclusive of an ICS. This paper provides a new paradigm of ISMS for
ICSs, which will be shown to be more suitable than the existing ISMS.
PMID- 25136658
TI - The role of IL-33 in host response to Candida albicans.
AB - BACKGROUND: Interleukin (IL) 33 is a recently identified pleiotropic cytokine
that influences the activity of multiple cell types and orchestrates complex
innate and adaptive immune responses. METHODS: We performed an extensive review
of the literature published between 2005 and 2013 on IL-33 and related cytokines,
their functions, and their regulation of the immune system following Candida
albicans colonization. Our literature review included cross-references from
retrieved articles and specific data from our own studies. RESULTS: IL-33 (IL
1F11) is a recently identified member of the IL-1 family of cytokines.
Accumulating evidence suggests a pivotal role of the IL-33/ST2 axis in host
immune defense against fungal pathogens, including C. albicans. IL-33 induces a
Th2-type inflammatory response and activates both innate and adaptive immunity.
Studies in animal models have shown that Th2 inflammatory responses have a
beneficial role in immunity against gastrointestinal and systemic infections by
Candida spp. CONCLUSIONS: This review summarizes the most important clinical
studies and case reports describing the beneficial role of IL-33 in immunity and
host defense mechanisms against pathogenic fungi. The finding that the IL-33/ST2
axis is involved in therapeutic target has implications for the prevention and
treatment of inflammatory diseases, including acute or chronic candidiasis.
PMID- 25136660
TI - Induced effects of transcranial magnetic stimulation on the autonomic nervous
system and the cardiac rhythm.
AB - Several standard protocols based on repetitive transcranial magnetic stimulation
(rTMS) have been employed for treatment of a variety of neurological disorders.
Despite their advantages in patients that are retractable to medication, there is
a lack of knowledge about the effects of rTMS on the autonomic nervous system
that controls the cardiovascular system. Current understanding suggests that the
shape of the so-called QRS complex together with the size of the different
segments and intervals between the PQRST deflections of the heart could predict
the nature of the different arrhythmias and ailments affecting the heart. This
preliminary study involving 10 normal subjects from 20 to 30 years of age
demonstrated that rTMS can induce changes in the heart rhythm. The autonomic
activity that controls the cardiac rhythm was indeed altered by an rTMS session
targeting the motor cortex using intensity below the subject's motor threshold
and lasting no more than 5 minutes. The rTMS activation resulted in a reduction
of the RR intervals (cardioacceleration) in most cases. Most of these cases also
showed significant changes in the Poincare plot descriptor SD2 (long-term
variability), the area under the low frequency (LF) power spectrum density curve,
and the low frequency to high frequency (LF/HF) ratio. The RR intervals changed
significantly in specific instants of time during rTMS activation showing either
heart rate acceleration or heart rate deceleration.
PMID- 25136661
TI - An improved Pearson's correlation proximity-based hierarchical clustering for
mining biological association between genes.
AB - Microarray gene expression datasets has concerned great awareness among molecular
biologist, statisticians, and computer scientists. Data mining that extracts the
hidden and usual information from datasets fails to identify the most significant
biological associations between genes. A search made with heuristic for standard
biological process measures only the gene expression level, threshold, and
response time. Heuristic search identifies and mines the best biological
solution, but the association process was not efficiently addressed. To monitor
higher rate of expression levels between genes, a hierarchical clustering model
was proposed, where the biological association between genes is measured
simultaneously using proximity measure of improved Pearson's correlation (PCPHC).
Additionally, the Seed Augment algorithm adopts average linkage methods on rows
and columns in order to expand a seed PCPHC model into a maximal global PCPHC (GL
PCPHC) model and to identify association between the clusters. Moreover, a GL
PCPHC applies pattern growing method to mine the PCPHC patterns. Compared to
existing gene expression analysis, the PCPHC model achieves better performance.
Experimental evaluations are conducted for GL-PCPHC model with standard benchmark
gene expression datasets extracted from UCI repository and GenBank database in
terms of execution time, size of pattern, significance level, biological
association efficiency, and pattern quality.
PMID- 25136662
TI - The design and implementation of postprocessing for depth map on real-time
extraction system.
AB - Depth estimation becomes the key technology to resolve the communications of the
stereo vision. We can get the real-time depth map based on hardware, which cannot
implement complicated algorithm as software, because there are some restrictions
in the hardware structure. Eventually, some wrong stereo matching will inevitably
exist in the process of depth estimation by hardware, such as FPGA. In order to
solve the problem a postprocessing function is designed in this paper. After
matching cost unique test, the both left-right and right-left consistency check
solutions are implemented, respectively; then, the cavities in depth maps can be
filled by right depth values on the basis of right-left consistency check
solution. The results in the experiments have shown that the depth map extraction
and postprocessing function can be implemented in real time in the same system;
what is more, the quality of the depth maps is satisfactory.
PMID- 25136663
TI - Realistic facial expression of virtual human based on color, sweat, and tears
effects.
AB - Generating extreme appearances such as scared awaiting sweating while happy fit
for tears (cry) and blushing (anger and happiness) is the key issue in achieving
the high quality facial animation. The effects of sweat, tears, and colors are
integrated into a single animation model to create realistic facial expressions
of 3D avatar. The physical properties of muscles, emotions, or the fluid
properties with sweating and tears initiators are incorporated. The action units
(AUs) of facial action coding system are merged with autonomous AUs to create
expressions including sadness, anger with blushing, happiness with blushing, and
fear. Fluid effects such as sweat and tears are simulated using the particle
system and smoothed-particle hydrodynamics (SPH) methods which are combined with
facial animation technique to produce complex facial expressions. The effects of
oxygenation of the facial skin color appearance are measured using the pulse
oximeter system and the 3D skin analyzer. The result shows that virtual human
facial expression is enhanced by mimicking actual sweating and tears simulations
for all extreme expressions. The proposed method has contribution towards the
development of facial animation industry and game as well as computer graphics.
PMID- 25136664
TI - Hematite nanoparticles-modified electrode based electrochemical sensing platform
for dopamine.
AB - Hematite (alpha-Fe2O3) nanoparticles were synthesized by the solid transformation
of ferrous hydroxide and ferrihydrite in hydrothermal condition. The as-prepared
alpha-Fe2O3 nanoparticles were characterized by UV-vis, PL, XRD, Raman, TEM, AFM,
FESEM, and EDX analysis. The experimental results indicated the formation of
uniform hematite nanoparticles with an average size of 45 nm and perfect
crystallinity. The electrochemical behavior of a GC/alpha-Fe2O3 electrode was
studied using CV and EIS techniques with an electrochemical probe, [Fe(CN)6](3-/4
) redox couple. The electrocatalytic activity was investigated toward DA
oxidation in a phosphate buffer solution (pH 6.8) by varying different
experimental parameters. The chronoamperometric study showed a linear response in
the range of 0-2 MUM with LoD of 1.6 MUM for DA. Square wave voltammetry showed a
linear response in the range of 0-35 MUM with LoD of 236 nM for DA.
PMID- 25136665
TI - Kinetics of mushroom tyrosinase and melanogenesis inhibition by N-acetyl
pentapeptides.
AB - We investigated the kinetics of 4N-acetyl-pentapeptides, Ac-P1, Ac-P2, Ac-P3, and
Ac-P4, regarding inhibition of mushroom tyrosinase activity. The peptides
sequences of Ac-P1, Ac-P2, Ac-P3, and Ac-P4 were Ac-RSRFK, Ac-KSRFR, Ac-KSSFR,
and Ac-RSRFS, respectively. The 4N-acetyl-pentapeptides were able to reduce the
oxidation of l-DOPA by tyrosinase in a dose-dependent manner. Of the 4N-acetyl
pentapeptides, only Ac-P4 exhibited lag time (80 s) at a concentration of 0.5
mg/mL. The tyrosinase inhibitory effects of Ac-P4 (IC50 0.29 mg/mL) were more
effective than those of Ac-P1, Ac-P2, and Ac-P3, in which IC50s were 0.75 mg/mL,
0.78 mg/mL, and 0.81 mg/mL, respectively. Kinetic analysis demonstrated that all
4N-acetyl-pentapeptides were mixed-type tyrosinase inhibitors. Furthermore, 0.1
mg/mL of Ac-P4 exhibited significant melanogenesis inhibition on B16F10 melanoma
cells and was more effective than kojic acid. The melanogenesis inhibition of Ac
P4 was dose-dependent and did not induce any cytotoxicity on B16F10 melanoma
cells.
PMID- 25136667
TI - Optimization of self-directed target coverage in wireless multimedia sensor
network.
AB - Video and image sensors in wireless multimedia sensor networks (WMSNs) have
directed view and limited sensing angle. So the methods to solve target coverage
problem for traditional sensor networks, which use circle sensing model, are not
suitable for WMSNs. Based on the FoV (field of view) sensing model and FoV disk
model proposed, how expected multimedia sensor covers the target is defined by
the deflection angle between target and the sensor's current orientation and the
distance between target and the sensor. Then target coverage optimization
algorithms based on expected coverage value are presented for single-sensor
single-target, multisensor single-target, and single-sensor multitargets problems
distinguishingly. Selecting the orientation that sensor rotated to cover every
target falling in the FoV disk of that sensor for candidate orientations and
using genetic algorithm to multisensor multitargets problem, which has NP
complete complexity, then result in the approximated minimum subset of sensors
which covers all the targets in networks. Simulation results show the algorithm's
performance and the effect of number of targets on the resulting subset.
PMID- 25136666
TI - Turbulence model sensitivity and scour gap effect of unsteady flow around pipe: a
CFD study.
AB - A numerical investigation of incompressible and transient flow around circular
pipe has been carried out at different five gap phases. Flow equations such as
Navier-Stokes and continuity equations have been solved using finite volume
method. Unsteady horizontal velocity and kinetic energy square root profiles are
plotted using different turbulence models and their sensitivity is checked
against published experimental results. Flow parameters such as horizontal
velocity under pipe, pressure coefficient, wall shear stress, drag coefficient,
and lift coefficient are studied and presented graphically to investigate the
flow behavior around an immovable pipe and scoured bed.
PMID- 25136670
TI - Knee joint biomechanics in high flexion.
PMID- 25136669
TI - Micropropagation of an exotic ornamental plant, Calathea crotalifera, for
production of high quality plantlets.
AB - A successful protocol was established for micropropagation in two selected
varieties of exotic ornamental plants, Calathea crotalifera. The effects of
different sterilization techniques, explant type, and the combination and
concentration of plant growth regulators on shoots induction were studied. The
axillary shoot buds explants sprouted from rhizomes in soil free conditions
showed high induction rate of shoots with lowest contamination percentage when
treated with combination of 30% (v/v) NaOCl, 70% (v/v) ethanol, and 0.3% (w/v)
HgCl2. In the present study, the highest number of multiple shoots was obtained
in MS basal medium supplemented with 3.5 mg/L 6-Benzylaminopurine (BAP), 1.0 mg/L
1-Naphthaleneacetic acid (NAA), 3% sucrose, and 6 g/L plant agar for both
varieties and was used as multiplication medium. Microshoots were highly induced
when the young shoot bud explants were incised longitudinally prior subculture.
Chlorophyll analysis was studied to test the effects of activated charcoal and L
glutamine on reduction of necrosis problem. The maximum roots induction was
recorded on MS medium supplemented with 1.0 mg/L 1-Naphthaleneacetic acid (NAA)
compared to indolebutyric acid (IBA). The complete regenerated plantlets were
successfully acclimatized in the soilless medium under greenhouse condition. This
is the first report of rapid mass propagation for C. crotalifera.
PMID- 25136668
TI - Neoadjuvant chemotherapy with FOLFOX4 regimen to treat advanced gastric cancer
improves survival without increasing adverse events: a retrospective cohort study
from a Chinese center.
AB - BACKGROUND/AIM: To evaluate the clinical efficacy of FOLFOX4 (5
fluomumcil/leucovorin combined and oxaliplatin) neoadjuvant chemotherapy for
advanced gastric cancer (AGC). PATIENTS AND METHODS: Fifty-eight AGC patients
were enrolled in this retrospective cohort study, 23 in the neoadjuvant group and
35 in the adjuvant group. R0 resection, survival, and adverse events were
compared. RESULTS: The two groups were well-matched, with no significant
differences in R0 resection rate (82.6% versus 82.0%) and number of lymph nodes
dissection (16 (0-49) versus 13 (3-40)) between the two groups (P > 0.05). The
number of lymph node metastases in the neoadjuvant group (3 (0-14)) was
significantly fewer than that in the adjuvant group (6 (0-27)) (P = 0.04). The
neoadjuvant group had significantly better median overall survival (29.0 versus
22.0 months) and 3-year survival rate (73.9% versus 40.0%) than the adjuvant
group (P = 0.013). The positive expression rate of Ki-67 in the neoadjuvant group
(40.0%, 8/20) was lower than that in the adjuvant group (74.2%, 23/31; P =
0.015). CONCLUSION: The FOLFOX4 neoadjuvant chemotherapy could improve survival
without increasing adverse events in patients with AGC.
PMID- 25136671
TI - The role of antioxidant enzymes in adaptive responses to sheath blight
infestation under different fertilization rates and hill densities.
AB - Sheath blight of rice, caused by Rhizoctonia solani, is one of the most
devastating rice diseases worldwide. No rice cultivar has been found to be
completely resistant to this fungus. Identifying antioxidant enzymes activities
(activity of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT))
and malondialdehyde content (MDA) responding to sheath blight infestation is
imperative to understand the defensive mechanism systems of rice. In the present
study, two inoculation methods (toothpick and agar block method) were tested in
double-season rice. Toothpick method had greater lesion length than agar block
method in late season. A higher MDA content was found under toothpick method
compared with agar block method, which led to greater POD and SOD activities.
Dense planting caused higher lesion length resulting in a higher MDA content,
which also subsequently stimulated higher POD and SOD activity. Sheath blight
severity was significantly related to the activity of antioxidant enzyme during
both seasons. The present study implies that rice plants possess a system of
antioxidant protective enzymes which helps them in adaptation to sheath blight
infection stresses. Several agronomic practices, such as rational use of
fertilizers and optimum planting density, involved in regulating antioxidant
protective enzyme systems can be regarded as promising strategy to suppress the
sheath blight development.
PMID- 25136672
TI - An evaluation and implementation of rule-based Home Energy Management System
using the Rete algorithm.
AB - In recent years, sensors become popular and Home Energy Management System (HEMS)
takes an important role in saving energy without decrease in QoL (Quality of
Life). Currently, many rule-based HEMSs have been proposed and almost all of them
assume "IF-THEN" rules. The Rete algorithm is a typical pattern matching
algorithm for IF-THEN rules. Currently, we have proposed a rule-based Home Energy
Management System (HEMS) using the Rete algorithm. In the proposed system, rules
for managing energy are processed by smart taps in network, and the loads for
processing rules and collecting data are distributed to smart taps. In addition,
the number of processes and collecting data are reduced by processing rules based
on the Rete algorithm. In this paper, we evaluated the proposed system by
simulation. In the simulation environment, rules are processed by a smart tap
that relates to the action part of each rule. In addition, we implemented the
proposed system as HEMS using smart taps.
PMID- 25136673
TI - Model of close packing for determination of the major characteristics of the
liquid dispersions components.
AB - We introduce a close packing model of the particles from the disperse phase of a
liquid dispersion. With this model, we find the sediment volumes, the emergent,
and the bound dispersion medium. We formulate a new approach for determining the
equivalent radii of the particles from the sediment and the emergent (different
from the Stokes method). We also describe an easy manner to apply algebraic
method for determining the average volumetric mass densities of the ultimate
sediment and emergent, as well as the free dispersion medium (without using any
pycnometers or densitometers). The masses of the different components and the
density of the dispersion phase in the investigated liquid dispersion are also
determined by means of the established densities. We introduce for the first time
a dimensionless scale for numeric characterization and therefore an index for
predicting the sedimentation stability of liquid dispersions in case of straight
and/or reverse sedimentation. We also find the quantity of the pure substance
(without pouring out or drying) in the dispersion phase of the liquid
dispersions.
PMID- 25136674
TI - Covert network analysis for key player detection and event prediction using a
hybrid classifier.
AB - National security has gained vital importance due to increasing number of
suspicious and terrorist events across the globe. Use of different subfields of
information technology has also gained much attraction of researchers and
practitioners to design systems which can detect main members which are actually
responsible for such kind of events. In this paper, we present a novel method to
predict key players from a covert network by applying a hybrid framework. The
proposed system calculates certain centrality measures for each node in the
network and then applies novel hybrid classifier for detection of key players.
Our system also applies anomaly detection to predict any terrorist activity in
order to help law enforcement agencies to destabilize the involved network. As a
proof of concept, the proposed framework has been implemented and tested using
different case studies including two publicly available datasets and one local
network.
PMID- 25136675
TI - Protection of HEVC video delivery in vehicular networks with RaptorQ codes.
AB - With future vehicles equipped with processing capability, storage, and
communications, vehicular networks will become a reality. A vast number of
applications will arise that will make use of this connectivity. Some of them
will be based on video streaming. In this paper we focus on HEVC video coding
standard streaming in vehicular networks and how it deals with packet losses with
the aid of RaptorQ, a Forward Error Correction scheme. As vehicular networks are
packet loss prone networks, protection mechanisms are necessary if we want to
guarantee a minimum level of quality of experience to the final user. We have run
simulations to evaluate which configurations fit better in this type of
scenarios.
PMID- 25136677
TI - Induced unbalanced linguistic ordered weighted average and its application in
multiperson decision making.
AB - Linguistic variables are very useful to evaluate alternatives in decision making
problems because they provide a vocabulary in natural language rather than
numbers. Some aggregation operators for linguistic variables force the use of a
symmetric and uniformly distributed set of terms. The need to relax these
conditions has recently been posited. This paper presents the induced unbalanced
linguistic ordered weighted average (IULOWA) operator. This operator can deal
with a set of unbalanced linguistic terms that are represented using fuzzy sets.
We propose a new order-inducing criterion based on the specificity and fuzziness
of the linguistic terms. Different relevancies are given to the fuzzy values
according to their uncertainty degree. To illustrate the behaviour of the
precision-based IULOWA operator, we present an environmental assessment case
study in which a multiperson multicriteria decision making model is applied.
PMID- 25136678
TI - An ant colony optimization based feature selection for web page classification.
AB - The increased popularity of the web has caused the inclusion of huge amount of
information to the web, and as a result of this explosive information growth,
automated web page classification systems are needed to improve search engines'
performance. Web pages have a large number of features such as HTML/XML tags,
URLs, hyperlinks, and text contents that should be considered during an automated
classification process. The aim of this study is to reduce the number of features
to be used to improve runtime and accuracy of the classification of web pages. In
this study, we used an ant colony optimization (ACO) algorithm to select the best
features, and then we applied the well-known C4.5, naive Bayes, and k nearest
neighbor classifiers to assign class labels to web pages. We used the WebKB and
Conference datasets in our experiments, and we showed that using the ACO for
feature selection improves both accuracy and runtime performance of
classification. We also showed that the proposed ACO based algorithm can select
better features with respect to the well-known information gain and chi square
feature selection methods.
PMID- 25136679
TI - An effective approach to improving low-cost GPS positioning accuracy in real-time
navigation.
AB - Positioning accuracy is a challenging issue for location-based applications using
a low-cost global positioning system (GPS). This paper presents an effective
approach to improving the positioning accuracy of a low-cost GPS receiver for
real-time navigation. The proposed method precisely estimates position by
combining vehicle movement direction, velocity averaging, and distance between
waypoints using coordinate data (latitude, longitude, time, and velocity) of the
GPS receiver. The previously estimated precious reference point, coordinate
translation, and invalid data check also improve accuracy. In order to evaluate
the performance of the proposed method, we conducted an experiment using a GARMIN
GPS 19xHVS receiver attached to a car and used Google Maps to plot the processed
data. The proposed method achieved improvement of 4-10 meters in several
experiments. In addition, we compared the proposed approach with two other state
of-the-art methods: recursive averaging and ARMA interpolation. The experimental
results show that the proposed approach outperforms other state-of-the-art
methods in terms of positioning accuracy.
PMID- 25136680
TI - Back analysis of geomechanical parameters in underground engineering using
artificial bee colony.
AB - Accurate geomechanical parameters are critical in tunneling excavation, design,
and supporting. In this paper, a displacements back analysis based on artificial
bee colony (ABC) algorithm is proposed to identify geomechanical parameters from
monitored displacements. ABC was used as global optimal algorithm to search the
unknown geomechanical parameters for the problem with analytical solution. To the
problem without analytical solution, optimal back analysis is time-consuming, and
least square support vector machine (LSSVM) was used to build the relationship
between unknown geomechanical parameters and displacement and improve the
efficiency of back analysis. The proposed method was applied to a tunnel with
analytical solution and a tunnel without analytical solution. The results show
the proposed method is feasible.
PMID- 25136681
TI - Characteristics of wind velocity and temperature change near an escarpment-shaped
road embankment.
AB - Artificial structures such as embankments built during the construction of
highways influence the surrounding airflow. Various types of damage can occur due
to changes in the wind velocity and temperature around highway embankments.
However, no study has accurately measured micrometeorological changes (wind
velocity and temperature) due to embankments. This study conducted a wind tunnel
test and field measurement to identify changes in wind velocity and temperature
before and after the construction of embankments around roads. Changes in wind
velocity around an embankment after its construction were found to be influenced
by the surrounding wind velocity, wind angle, and the level difference and
distance from the embankment. When the level difference from the embankment was
large and the distance was up to 3H, the degree of wind velocity declines was
found to be large. In changes in reference wind velocities around the embankment,
wind velocity increases were not proportional to the rate at which wind
velocities declined. The construction of the embankment influenced surrounding
temperatures. The degree of temperature change was large in locations with large
level differences from the embankment at daybreak and during evening hours when
wind velocity changes were small.
PMID- 25136682
TI - Big data: survey, technologies, opportunities, and challenges.
AB - Big Data has gained much attention from the academia and the IT industry. In the
digital and computing world, information is generated and collected at a rate
that rapidly exceeds the boundary range. Currently, over 2 billion people
worldwide are connected to the Internet, and over 5 billion individuals own
mobile phones. By 2020, 50 billion devices are expected to be connected to the
Internet. At this point, predicted data production will be 44 times greater than
that in 2009. As information is transferred and shared at light speed on optic
fiber and wireless networks, the volume of data and the speed of market growth
increase. However, the fast growth rate of such large data generates numerous
challenges, such as the rapid growth of data, transfer speed, diverse data, and
security. Nonetheless, Big Data is still in its infancy stage, and the domain has
not been reviewed in general. Hence, this study comprehensively surveys and
classifies the various attributes of Big Data, including its nature, definitions,
rapid growth rate, volume, management, analysis, and security. This study also
proposes a data life cycle that uses the technologies and terminologies of Big
Data. Future research directions in this field are determined based on
opportunities and several open issues in Big Data domination. These research
directions facilitate the exploration of the domain and the development of
optimal techniques to address Big Data.
PMID- 25136676
TI - Vascular calcification and renal bone disorders.
AB - At the early stage of chronic kidney disease (CKD), the systemic mineral
metabolism and bone composition start to change. This alteration is known as
chronic kidney disease-mineral bone disorder (CKD-MBD). It is well known that the
bone turnover disorder is the most common complication of CKD-MBD. Besides, CKD
patients usually suffer from vascular calcification (VC), which is highly
associated with mortality. Many factors regulate the VC mechanism, which include
imbalances in serum calcium and phosphate, systemic inflammation, RANK/RANKL/OPG
triad, aldosterone, microRNAs, osteogenic transdifferentiation, and effects of
vitamins. These factors have roles in both promoting and inhibiting VC. Patients
with CKD usually have bone turnover problems. Patients with high bone turnover
have increase of calcium and phosphate release from the bone. By contrast, when
bone turnover is low, serum calcium and phosphate levels are frequently
maintained at high levels because the reservoir functions of bone decrease. Both
of these conditions will increase the possibility of VC. In addition, the
calcified vessel may secrete FGF23 and Wnt inhibitors such as sclerostin, DKK-1,
and secreted frizzled-related protein to prevent further VC. However, all of them
may fight back the inhibition of bone formation resulting in fragile bone. There
are several ways to treat VC depending on the bone turnover status of the
individual. The main goals of therapy are to maintain normal bone turnover and
protect against VC.
PMID- 25136683
TI - Quality of protection evaluation of security mechanisms.
AB - Recent research indicates that during the design of teleinformatic system the
tradeoff between the systems performance and the system protection should be
made. The traditional approach assumes that the best way is to apply the
strongest possible security measures. Unfortunately, the overestimation of
security measures can lead to the unreasonable increase of system load. This is
especially important in multimedia systems where the performance has critical
character. In many cases determination of the required level of protection and
adjustment of some security measures to these requirements increase system
efficiency. Such an approach is achieved by means of the quality of protection
models where the security measures are evaluated according to their influence on
the system security. In the paper, we propose a model for QoP evaluation of
security mechanisms. Owing to this model, one can quantify the influence of
particular security mechanisms on ensuring security attributes. The methodology
of our model preparation is described and based on it the case study analysis is
presented. We support our method by the tool where the models can be defined and
QoP evaluation can be performed. Finally, we have modelled TLS cryptographic
protocol and presented the QoP security mechanisms evaluation for the selected
versions of this protocol.
PMID- 25136684
TI - (n - 1)-Step derivations on n-groupoids: the case n = 3.
AB - We define a ranked trigroupoid as a natural followup on the idea of a ranked
bigroupoid. We consider the idea of a derivation on such a trigroupoid as
representing a two-step process on a pair of ranked bigroupoids where the mapping
d is a self-derivation at each step. Following up on this idea we obtain several
results and conclusions of interest. We also discuss the notion of a couplet (D,
d) on X, consisting of a two-step derivation d and its square D = d ? d, for
example, whose defining property leads to further observations on the underlying
ranked trigroupoids also.
PMID- 25136685
TI - Minimize the percentage of noise in biomedical images using neural networks.
AB - The overall goal of the research is to improve the quality of biomedical image
for telemedicine with minimum percentages of noise in the retrieved image and to
take less computation time. The novelty of this technique lies in the
implementation of spectral coding for biomedical images using neural networks in
order to accomplish the above objectives. This work is in continuity of an
ongoing research project aimed at developing a system for efficient image
compression approach for telemedicine in Saudi Arabia. We compare the efficiency
of this technique against existing image compression techniques, namely,
JPEG2000, in terms of compression ratio, peak signal to noise ratio (PSNR), and
computation time. To our knowledge, the research is the primary in providing a
comparative study with other techniques used in the compression of biomedical
images. This work explores and tests biomedical images such as X-rays, computed
tomography (CT), magnetic resonance imaging (MRI), and positron emission
tomography (PET).
PMID- 25136687
TI - Fire propagation performance of intumescent fire protective coatings using
eggshells as a novel biofiller.
AB - This paper aims to synthesize and characterize an effective intumescent fire
protective coating that incorporates eggshell powder as a novel biofiller. The
performances of thermal stability, char formation, fire propagation, water
resistance, and adhesion strength of coatings have been evaluated. A few
intumescent flame-retardant coatings based on these three ecofriendly fire
retardant additives ammonium polyphosphate phase II, pentaerythritol and melamine
mixed together with flame-retardant fillers, and acrylic binder have been
prepared and designed for steel. The fire performance of the coatings has
conducted employing BS 476: Part 6-Fire propagation test. The foam structures of
the intumescent coatings have been observed using field emission scanning
electron microscopy. On exposure, the coated specimens' B, C, and D had been
certified to be Class 0 due to the fact that their fire propagation indexes were
less than 12. Incorporation of ecofriendly eggshell, biofiller into formulation D
led to excellent performance in fire stopping (index value, (I) = 4.3) and
antioxidation of intumescent coating. The coating is also found to be quite
effective in water repellency, uniform foam structure, and adhesion strength.
PMID- 25136686
TI - Lymphocyte oxidative stress/genotoxic effects are related to serum IgG and IgA
levels in coke oven workers.
AB - We investigated oxidative stress/genotoxic effects levels, immunoglobulin levels,
polycyclic aromatic hydrocarbons (PAHs) levels exposed in 126 coke oven workers
and in 78 control subjects, and evaluated the association between oxidative
stress/genotoxic effects levels and immunoglobulin levels. Significant
differences were observed in biomarkers, including 1-hydroxypyrene levels,
employment time, percentages of alcohol drinkers, MDA, 8-OHdG levels, CTL levels
and CTM, MN, CA frequency, and IgG, IgA levels between the control and exposed
groups. Slightly higher 1-OHP levels in smoking users were observed. For the dose
response relationship of IgG, IgA, IgM, and IgE by 1-OHP, each one percentage
increase in urinary 1-OHP generates a 0.109%, 0.472%, 0.051%, and 0.067% decrease
in control group and generates a 0.312%, 0.538%, 0.062%, and 0.071% decrease in
exposed group, respectively. Except for age, alcohol and smoking status, IgM, and
IgE, a significant correlation in urinary 1-OHP and other biomarkers in the total
population was observed. Additionally, a significant negative correlation in
genotoxic/oxidative damage biomarkers of MDA, 8-OH-dG, CTL levels, and
immunoglobins of IgG and IgA levels, especially in coke oven workers, was found.
These data suggest that oxidative stress/DNA damage induced by PAHs may play a
role in toxic responses for PAHs in immunological functions.
PMID- 25136688
TI - Automating risk analysis of software design models.
AB - The growth of the internet and networked systems has exposed software to an
increased amount of security threats. One of the responses from software
developers to these threats is the introduction of security activities in the
software development lifecycle. This paper describes an approach to reduce the
need for costly human expertise to perform risk analysis in software, which is
common in secure development methodologies, by automating threat modeling.
Reducing the dependency on security experts aims at reducing the cost of secure
development by allowing non-security-aware developers to apply secure development
with little to no additional cost, making secure development more accessible. To
automate threat modeling two data structures are introduced, identification trees
and mitigation trees, to identify threats in software designs and advise
mitigation techniques, while taking into account specification requirements and
cost concerns. These are the components of our model for automated threat
modeling, AutSEC. We validated AutSEC by implementing it in a tool based on data
flow diagrams, from the Microsoft security development methodology, and applying
it to VOMS, a grid middleware component, to evaluate our model's performance.
PMID- 25136690
TI - A fuzzy-decision based approach for Composite event detection in wireless sensor
networks.
AB - The event detection is one of the fundamental researches in wireless sensor
networks (WSNs). Due to the consideration of various properties that reflect
events status, the Composite event is more consistent with the objective world.
Thus, the research of the Composite event becomes more realistic. In this paper,
we analyze the characteristics of the Composite event; then we propose a
criterion to determine the area of the Composite event and put forward a
dominating set based network topology construction algorithm under random
deployment. For the unreliability of partial data in detection process and
fuzziness of the event definitions in nature, we propose a cluster-based two
dimensional tau-GAS algorithm and fuzzy-decision based composite event decision
mechanism. In the case that the sensory data of most nodes are normal, the two
dimensional tau-GAS algorithm can filter the fault node data effectively and
reduce the influence of erroneous data on the event determination. The Composite
event judgment mechanism which is based on fuzzy-decision holds the superiority
of the fuzzy-logic based algorithm; moreover, it does not need the support of a
huge rule base and its computational complexity is small. Compared to CollECT
algorithm and CDS algorithm, this algorithm improves the detection accuracy and
reduces the traffic.
PMID- 25136689
TI - Effect of intra-articular hyaluronic injection on postural stability and risk of
fall in patients with bilateral knee osteoarthritis.
AB - Knee osteoarthritis is a common cause of disability which influences the quality
of life. It is associated with impaired knee joint proprioception, which affects
postural stability. Postural stability is critical for mobility and physical
activities. Different types of treatment including nonsurgical and surgical are
used for knee osteoarthritis. Hyaluronic acid injection is a nonsurgical popular
treatment used worldwide. The aim of this study was to demonstrate the effect of
hyaluronic acid injections on postural stability in individuals with bilateral
knee osteoarthritis. Fifty patients aged between 50 and 70 years with mild and
moderate bilateral knee osteoarthritis participated in our study. They were
categorized into treatment (n = 25) and control (n = 25) groups. The treatment
group received five weekly hyaluronic acid injections for both knees, whereas the
control group did not receive any treatment. Postural stability and fall risk
were assessed using the Biodex Stability System and clinical "Timed Up and Go"
test. All the participants completed the study. The treatment group showed
significant decrease in postural stability and fall risk scores after five
hyaluronic acid injections. In contrast, the control group showed significant
increase. This study illustrated that five intra-articular hyaluronic acid
injections could significantly improve postural stability and fall risk in
bilateral knee osteoarthritis patients. This trial is registered with:
NCT02063373.
PMID- 25136692
TI - On Poisson nonlinear transformations.
AB - We construct the family of Poisson nonlinear transformations defined on the
countable sample space of nonnegative integers and investigate their trajectory
behavior. We have proved that these nonlinear transformations are regular.
PMID- 25136691
TI - Comparison of internal fixations for distal clavicular fractures based on loading
tests and finite element analyses.
AB - It is difficult to apply strong and stable internal fixation to a fracture of the
distal end of the clavicle because it is unstable, the distal clavicle fragment
is small, and the fractured region is near the acromioclavicular joint. In this
study, to identify a superior internal fixation method for unstable distal
clavicular fracture, we compared three types of internal fixation (tension band
wiring, scorpion, and LCP clavicle hook plate). Firstly, loading tests were
performed, in which fixations were evaluated using bending stiffness and
torsional stiffness as indices, followed by finite element analysis to evaluate
fixability using the stress and strain as indices. The bending and torsional
stiffness were significantly higher in the artificial clavicles fixed with the
two types of plate than in that fixed by tension band wiring (P < 0.05). No
marked stress concentration on the clavicle was noted in the scorpion because the
arm plate did not interfere with the acromioclavicular joint, suggesting that
favorable shoulder joint function can be achieved. The stability of fixation with
the LCP clavicle hook plate and the scorpion was similar, and plate fixations
were stronger than fixation by tension band wiring.
PMID- 25136693
TI - Mutation and chaos in nonlinear models of heredity.
AB - We shall explore a nonlinear discrete dynamical system that naturally occurs in
population systems to describe a transmission of a trait from parents to their
offspring. We consider a Mendelian inheritance for a single gene with three
alleles and assume that to form a new generation, each gene has a possibility to
mutate, that is, to change into a gene of the other kind. We investigate the
derived models and observe chaotic behaviors of such models.
PMID- 25136694
TI - Enhancement of the wear resistance and microhardness of aluminum alloy by Nd:YaG
laser treatment.
AB - Influence of laser treatment on mechanical properties, wear resistance, and
Vickers hardness of aluminum alloy was studied. The specimens were treated by
using Nd:YaG laser of energy 780 mj, wavelength 512 nm, and duration time 8 ns.
The wear behavior of the specimens was studied for all specimens before and after
treatment by Nd:YaG laser and the dry wear experiments were carried out by sing
pinon-disc technique. The specimens were machined as a disk with diameter of 25
mm and circular groove in depth of 3 mm. All specimens were conducted by scanning
electron microscopy (SEM), energy-dispersive X-ray fluorescence analysis (EDS),
optical microscopy, and Vickers hardness. The results showed that the dry wear
rate was decreased after laser hardening and increased Vickers hardness values by
ratio of 2.4:1. The results showed that the values of wear rate for samples
having circular grooves are less than samples without grooves after laser
treatment.
PMID- 25136695
TI - PLUNC proteins positivity in patients with chronic rhinosinusitis: a case-control
study.
AB - INTRODUCTION: Innate immunity is the first protection against microorganisms.
Nowadays, there is a growing interest in innate immune molecule known as palate,
lung, nasal epithelial clone (PLUNC). PLUNC is a specific product of the airways,
of approximately 25 kDa, encoded by adjacent genes found within a 300 kb region
of chromosome 20; these proteins must be detected predominantly in the upper
respiratory tract. MATERIALS AND METHODS: We performed a case-control study to
investigate the presence of this protein in nasal tissue of patients affected by
chronic rhinosinusitis. 59 patients were enrolled (44 cases, 15 controls). We
have examined the correlation between the presence of pathology and the PLUNC
proteins positivity. RESULTS: 100% of controls have a +++ rated PLUNC proteins
positivity, while cases have a lower percentage of positivity. We used chi (2)
statistical test to analyze the results of the study and there is a difference
statistically significant between cases and controls in PLUNC proteins
positivity. CONCLUSIONS: These observations suggest that, in response to agents
or chemical factors, nasal mucosal epithelium will react and produce PLUNC
proteins. So PLUNC proteins have a protective function on upper airways mucosa,
as we can see by evaluating the high positivity in control group.
PMID- 25136696
TI - Carbon dioxide absorption and release properties of pyrolysis products of
dolomite calcined in vacuum atmosphere.
AB - The decomposition of dolomite into CaO and MgO was performed at 1073 K in vacuum
and at 1273 K in an Ar atmosphere. The dolomite calcined in vacuum was found to
have a higher specific surface area and a higher micropore volume when compared
to the dolomite calcined in the Ar atmosphere. These pyrolysis products of
dolomite were reacted with CO2 at 673 K for 21.6 ks. On the absorption of CO2,
the formation of CaCO3 was observed. The degree of absorption of the dolomite
calcined in vacuum was determined to be above 50%, which was higher than the
degree of absorption of the dolomite calcined in the Ar atmosphere. The CO2
absorption and release procedures were repeated three times for the dolomite
calcined in vacuum. The specific surface area and micropore volume of calcined
dolomite decreased with successive repetitions of the CO2 absorption and release
cycles leading to a decrease in the degree of absorption of CO2.
PMID- 25136697
TI - A secure 3-way routing protocols for intermittently connected mobile ad hoc
networks.
AB - The mobile ad hoc network may be partially connected or it may be disconnected in
nature and these forms of networks are termed intermittently connected mobile ad
hoc network (ICMANET). The routing in such disconnected network is commonly an
arduous task. Many routing protocols have been proposed for routing in ICMANET
since decades. The routing techniques in existence for ICMANET are, namely,
flooding, epidemic, probabilistic, copy case, spray and wait, and so forth. These
techniques achieve an effective routing with minimum latency, higher delivery
ratio, lesser overhead, and so forth. Though these techniques generate effective
results, in this paper, we propose novel routing algorithms grounded on agent and
cryptographic techniques, namely, location dissemination service (LoDiS) routing
with agent AES, A-LoDiS with agent AES routing, and B-LoDiS with agent AES
routing, ensuring optimal results with respect to various network routing
parameters. The algorithm along with efficient routing ensures higher degree of
security. The security level is cited testing with respect to possibility of
malicious nodes into the network. This paper also aids, with the comparative
results of proposed algorithms, for secure routing in ICMANET.
PMID- 25136698
TI - The Polya-Szego principle and the anisotropic convex Lorentz-Sobolev inequality.
AB - An anisotropic convex Lorentz-Sobolev inequality is established, which extends
Ludwig, Xiao, and Zhang's result to any norm from Euclidean norm, and the
geometric analogue of this inequality is given. In addition, it implies that the
(anisotropic) Polya-Szego principle is shown.
PMID- 25136699
TI - A hybrid wavelet transform based short-term wind speed forecasting approach.
AB - It is important to improve the accuracy of wind speed forecasting for wind parks
management and wind power utilization. In this paper, a novel hybrid approach
known as WTT-TNN is proposed for wind speed forecasting. In the first step of the
approach, a wavelet transform technique (WTT) is used to decompose wind speed
into an approximate scale and several detailed scales. In the second step, a two
hidden-layer neural network (TNN) is used to predict both approximated scale and
detailed scales, respectively. In order to find the optimal network architecture,
the partial autocorrelation function is adopted to determine the number of
neurons in the input layer, and an experimental simulation is made to determine
the number of neurons within each hidden layer in the modeling process of TNN.
Afterwards, the final prediction value can be obtained by the sum of these
prediction results. In this study, a WTT is employed to extract these different
patterns of the wind speed and make it easier for forecasting. To evaluate the
performance of the proposed approach, it is applied to forecast Hexi Corridor of
China's wind speed. Simulation results in four different cases show that the
proposed method increases wind speed forecasting accuracy.
PMID- 25136700
TI - Image inpainting methods evaluation and improvement.
AB - With the upgrowing of digital processing of images and film archiving, the need
for assisted or unsupervised restoration required the development of a series of
methods and techniques. Among them, image inpainting is maybe the most impressive
and useful. Based on partial derivative equations or texture synthesis, many
other hybrid techniques have been proposed recently. The need for an analytical
comparison, beside the visual one, urged us to perform the studies shown in the
present paper. Starting with an overview of the domain, an evaluation of the five
methods was performed using a common benchmark and measuring the PSNR.
Conclusions regarding the performance of the investigated algorithms have been
presented, categorizing them in function of the restored image structure. Based
on these experiments, we have proposed an adaptation of Oliveira's and Hadhoud's
algorithms, which are performing well on images with natural defects.
PMID- 25136701
TI - Computational fluid dynamics modelling of microfluidic channel for
dielectrophoretic BioMEMS application.
AB - We propose a strategy for optimizing distribution of flow in a typical benchtop
microfluidic chamber for dielectrophoretic application. It is aimed at
encouraging uniform flow velocity along the whole analysis chamber in order to
ensure DEP force is evenly applied to biological particle. Via the study, we have
come up with a constructive strategy in improving the design of microfluidic
channel which will greatly facilitate the use of DEP system in laboratory and
primarily focus on the relationship between architecture and cell distribution,
by resorting to the tubular structure of blood vessels. The design was validated
by hydrodynamic flow simulation using COMSOL Multiphysics v4.2a software.
Simulations show that the presence of 2-level bifurcation has developed
portioning of volumetric flow which produced uniform flow across the channel.
However, further bifurcation will reduce the volumetric flow rate, thus causing
undesirable deposition of cell suspension around the chamber. Finally, an
improvement of microfluidic design with rounded corner is proposed to encourage a
uniform cell adhesion within the channel.
PMID- 25136702
TI - Thermodynamic analysis and optimization of a high temperature triple absorption
heat transformer.
AB - First law of thermodynamics has been used to analyze and optimize inclusively the
performance of a triple absorption heat transformer operating with LiBr/H2O as
the working pair. A thermodynamic model was developed in EES (engineering
equation solver) to estimate the performance of the system in terms of the most
essential parameters. The assumed parameters are the temperature of the main
components, weak and strong solutions, economizers' efficiencies, and bypass
ratios. The whole cycle is optimized by EES software from the viewpoint of
maximizing the COP via applying the direct search method. The optimization
results showed that the COP of 0.2491 is reachable by the proposed cycle.
PMID- 25136703
TI - Label-free in vitro visualization of particle uptake into human oral buccal
epithelial cells by confocal Raman microscopy.
AB - In this study, we present confocal Raman microscopy for chemically selective
analysis of a human buccal epithelial cell layer with a focus on label-free
visualization of particle uptake into the cells. We demonstrate the suitability
and benefit of this analytical technique in comparison to confocal fluorescence
microscopy for three dimensional imaging of in vitro cell models.
PMID- 25136704
TI - Association of provider-patient visit frequency and patient outcomes on
hemodialysis.
PMID- 25136705
TI - Unraveling the chemistry of the glomerular basement membrane.
PMID- 25136706
TI - Bortezomib, lenalidomide and dexamethasone (VRD) combination as salvage therapy
in refractory angioimmunoblastic T cell lymphoma.
PMID- 25136707
TI - Reflections: neurology and the humanities. A soliloquy in LP humility.
PMID- 25136708
TI - Author response.
PMID- 25136709
TI - Author response.
PMID- 25136710
TI - Photosynthetic efficiency and carbon concentration in terrestrial plants: the C4
and CAM solutions.
PMID- 25136711
TI - Cholera, 2013.
PMID- 25136712
TI - Health conditions for travellers to Saudi Arabia for the pilgrimage to Mecca
(Hajj), 2014.
PMID- 25136713
TI - Congress stalls on BRAIN Initiative funding.
PMID- 25136715
TI - Of pigs and people--WHO prepares to battle cysticercosis.
PMID- 25136714
TI - EC Chief Scientific Adviser position gets strong backing.
PMID- 25136716
TI - The Lancet Technology: August, 2014. Surgical training through the looking Glass.
PMID- 25136718
TI - Carlos Ribeiro.
PMID- 25136717
TI - Closing the carbon cycle.
PMID- 25136719
TI - The age of miracles.
PMID- 25136720
TI - Donald Nixon Ross.
PMID- 25136721
TI - Global Polio Eradication Initiative: 10th meeting of the Independent Monitoring
Board.
PMID- 25136722
TI - Monthly report on dracunculiasis cases, January-June 2014.
PMID- 25136723
TI - Authors' reply.
PMID- 25136724
TI - Authors' reply.
PMID- 25136725
TI - Possession of objectionable material (Med 12/228P).
PMID- 25136726
TI - Reply to Tai: On the inability of 10 soloists to tell apart Old Italian and new
violins at better than chance levels.
PMID- 25136727
TI - Review of the Blastobasinae of Costa Rica (Lepidoptera: Gelechioidea:
Blastobasidae).
AB - The Blastobasinae (Lepidoptera: Gelechioidea: Blastobasidae) of Costa Rica are
reviewed. Five new genera, Barbaloba, Hallicis, Koleps, Pheos, and Pseudokoleps,
and 101 new species are described. They include: Barbaloba jubae, B.
meleagrisellae, Hallicis bisetosellus, H. calvicula, Koleps angulatus, Pheos
aculeatus, Pseudokoleps akainae, Blastobasis abollae, B. achaea, B. aedes, B.
babae, B. balucis, B. beo, B. caetrae, B. chanes, B. custodis, B. dapis, B. deae,
B. deliciolarum, B. dicionis, B. echus, B. erae, B. fax, B. furtivus, B. iuanae,
B. lex, B. litis, B. lygdi, B. manto, B. neniae, B. nivis, B. orithyia, B.
paludis, B. phaedra, B. rotae, B. rotullae, B. tapetae, B. thyone, B. usurae, B.
vesta, B. xiphiae, Hypatopa actes, H. acus, H. agnae, H. arxcis, H. bilobata, H.
caedis, H. caepae, H. cladis, H. cotis, H. cotytto, H. crux, H. cyane, H. dicax,
H. dolo, H. dux, H. edax, H. eos, H. erato, H. fio, H. gena, H. hecate, H. hera,
H. hora, H. io, H. ira, H. leda, H. limae, H. lucina, H. joniella, H. juno, H.
manus, H. mora, H. musa, H. nex, H. nox, H. phoebe, H. pica, H. plebis, H. rabio,
H. rea, H. rego, H. rudis, H. sais, H. scobis, H. semela, H. solea, H. styga, H.
texla, H. texo, H. umbra, H. verax, H. vitis, H. vox, Pigritia dido, P. faux, P.
gruis, P. haha, P. sedis, P. stips, and P. ululae. Diagnoses, descriptions, and
type data are provided for each species. Photographs of imagos, illustrations of
wing venation for selected species, male and female genitalia, and distribution
maps are furnished. Keys to all genera in Blastobasinae and keys to all species
within each genus are provided to assist with identifications. In addition,
scanning electron micrographs of the inner surface of the dilated first antennal
flagellomere and associated sex scales for all Blastobasis are provided.
Blastobasis coffeaella (Busck, 1925), B. graminea Adamski, 1999, Hypatopa
tapadulcea Adamski, 1999, and Pigritia marjoriella Adamski, 1998 are redescribed.
PMID- 25136728
TI - Revision of the genus Erythromelana Townsend (Diptera: Tachinidae) and analysis
of its phylogeny and diversification.
AB - The Neotropics harbor an enormous diversity of tachinid flies (Diptera:
Tachinidae), yet the fauna remains poorly understood. This is especially true of
the tribe Blondeliini, which is particularly diverse in this region and in great
need of taxonomic attention. Here, the Neotropical blondeliine genus
Erythromelana Townsend is revised. This genus is widely distributed from southern
Mexico to northern Argentina, with the Andes being a hotspot of diversity. Known
hosts belong to the genus Eois Hubner (Lepidoptera: Geometridae). This revision
includes the redescription of three previously described species and the
description of 11 new species based on characteristics of adults and immatures.
The new species are E. arciforceps sp. nov., E. catarina sp. nov., E.
convexiforceps sp. nov., E. cryptica sp. nov., E. curvifrons sp. nov., E.
distincta sp. nov., E. ecuadoriana sp. nov., E. eois sp. nov., E. leptoforceps
sp. nov., E. napensis sp. nov., and E. woodi sp. nov. A morphological database of
62 characters was constructed to assess morphological variation within and among
species and species groups using Principal Components Analysis. Means and medians
for these morphological traits were calculated to infer phylogenetic
relationships using parsimony. Additionally, a maximum likelihood phylogenetic
analysis was performed using COI mtDNA sequences for a subset of eight species.
Nominal species E. obscurifrons (Wulp) is treated as a nomen dubium within
Erythromelana. Two species previously assigned to Erythromelana appear to
represent distinct genera with unclear relationships to this genus and are
reinstated as monotypic genera: Myiodoriops marginalis Townsend and
Euptilodegeeria obumbrata (Wulp), revived status. Biological and phylogenetic
data are used to infer modes of diversification within Erythromelana.
PMID- 25136730
TI - Preface: occupational diseases.
PMID- 25136729
TI - Current progress in Reactive Oxygen Species (ROS)-Responsive materials for
biomedical applications.
AB - Recently, significant progress has been made in developing "stimuli-sensitive"
biomaterials as a new therapeutic approach to interact with dynamic physiological
conditions. Reactive oxygen species (ROS) production has been implicated in
important pathophysiological events, such as atherosclerosis,aging, and cancer.
ROS are often overproduced locally in diseased cells and tissues, and they
individually and synchronously contribute to many of the abnormalities associated
with local pathogenesis. Therefore, the advantages of developing ROS-responsive
materials extend beyond site-specific targeting of therapeutic delivery, and
potentially include navigating,sensing, and repairing the cellular damages via
programmed changes in material properties. Here we review the mechanism and
development of biomaterials with ROS-induced solubility switch or degradation, as
well as their performance and potential for future biomedical applications.
PMID- 25136731
TI - Sex differences in the modulation of emotional processing by expectation.
AB - Many studies have reported sex differences in processing emotional events, the
valence of which are unknown in advance. The present study examined whether women
and men differ in processing emotional events when they do have such
expectations. Event-related potentials were recorded when participants were
presented with emotional pictures, the valence of which was either expected or
unexpected. For women, the modulation effect by expectation was found on the
early N2 response; for men, the effect was found on the late positive component.
Implications are discussed in light of evolutionary theories.
PMID- 25136733
TI - A rare cause of lower back pain.
PMID- 25136735
TI - 15 largest healthcare real estate investment trusts. Publicly traded healthcare
REITs ranked by market capitalization, as of May 31.
PMID- 25136734
TI - Blasts with rosette-like multinucleation in acute myeloid leukemia with complex
cytogenetic abnormalities.
PMID- 25136736
TI - Accountable care organizations by state. The number of accountable care
organizations per state, ranked by total number of ACOs.
PMID- 25136738
TI - Largest healthcare law firms. Based on a blended score of healthcare lawyers
employed in 2013 and AHLA membership as of June 5.
PMID- 25136739
TI - Bromination and accompanying rearrangement of the polycyclic oxetane 2,4
oxytwistane.
AB - Bromination of the polycyclic oxetane 2,4-oxytwistane (rac-(1R,3S,4R,7S,9R,11S)-2
oxatetracyclo[5.3.1.0(3,11).0(4,9)]undecane) was undertaken in order to form 2,4
dibromotwistane. The oxetane was subjected to the mild reagent combination
CBr4/Ph3P in a fashion similar to that for the Appel and Corey-Fuchs reactions.
NMR spectroscopy revealed that the isomeric dibromo compound 2,8
dibromoisotwistane (2,8-dibromotricyclo[4.3.1.0(3,7)]decane) was inadvertently
formed. The conversion was prevented by migration of a C-C bond within the
geometrically stressed C10 framework. Computational chemistry was used to model
the structure of the polycyclic oxetane and to assess the component of total ring
strain energy due to the four-membered heterocycle. Mechanistic aspects behind
the skeletal rearrangement are also discussed.
PMID- 25136737
TI - Franz Kafka and the doctor's dilemma.
PMID- 25136740
TI - Structurally nanocrystalline-electrically single crystalline ZnO-reduced graphene
oxide composites.
AB - ZnO, a wide bandgap semiconductor, has attracted much attention due to its
multifunctionality, such as transparent conducting oxide, light-emitting diode,
photocatalyst, and so on. To improve its performances in the versatile
applications, numerous hybrid strategies of ZnO with graphene have been
attempted, and various synergistic effects have been achieved in the ZnO-graphene
hybrid nanostructures. Here we report extraordinary charge transport behavior in
Al-doped ZnO (AZO)-reduced graphene oxide (RGO) nanocomposites. Although the most
challenging issue in semiconductor nanocomposites is their low mobilities, the
AZO-RGO nanocomposites exhibit single crystal-like Hall mobility despite the
large quantity of nanograin boundaries, which hinder the electron transport by
the scattering with trapped charges. Because of the significantly weakened grain
boundary barrier and the proper band alignment between the AZO and RGO, freely
conducting electrons across the nanograin boundaries can be realized in the
nanocomposites. This discovery of the structurally nanocrystalline-electrically
single crystalline composite demonstrates a new route for enhancing the
electrical properties in nanocomposites based on the hybrid strategy.
PMID- 25136742
TI - Tuning the gelation ability of racemic mixture by melamine: enhanced mechanical
rigidity and tunable nanoscale chirality.
AB - Understanding the relationship between molecular chirality of the gelators and
the properties of the assembled supramolecular gels could be very important for
developing novel functional soft matters. Although mixing the enantiomers with
different molar ratios has been proved to be useful for modulating supramolecular
assemblies, usually the racemates of different chiral molecules are not good
gelators. In this study, the coassembly of the glutamic acid-based bolaamphiphile
racemate and melamine was found to form hydrogels, while the assembly of the
racemate only produced precipitates. Remarkably, the racemic hydrogels show lower
CGC value, enhanced mechanical rigidity, and dual pH-responsive ability compared
to the pure enantiomer hydrogels. The gelation properties, nanoscale chirality,
and nanostructures of the racemic hydrogels can be regulated flexibly by changing
molar ratios of different molecular building blocks.
PMID- 25136743
TI - Dye-sensitized solar cells employing doubly or singly open-ended TiO2 nanotube
arrays: structural geometry and charge transport.
AB - We systematically investigated the charge transport properties of doubly or
singly open-ended TiO2 nanotube arrays (DNT and SNT, respectively) for their
utility as electrodes in dye-sensitized solar cells (DSCs). The SNT or DNT arrays
were transferred in a bottom-up (B-up) or top-up (T-up) configuration onto a
fluorine-doped tin oxide (FTO) substrate onto which had been deposited a 2 MUm
thick TiO2 nanoparticle (NP) interlayer. This process yielded four types of DSCs
prepared with SNTs (B-up or T-up) or DNT (B-up or T-up). The photovoltaic
performances of these DSCs were analyzed by measuring the dependence of the
charge transport on the DSC geometry. High resolution scanning electron
microscopy techniques were used to characterize the electrode cross sections, and
electrochemical impedance spectroscopy was used to characterize the electrical
connection at the interface between the NT array and the TiO2 NP interlayer. We
examined the effects of decorating the DNT or SNT arrays with small NPs (sNP@DNT
and sNP@SNT, respectively) in an effort to increase the extent of dye loading.
The DNT arrays decorated with small NPs performed better than the decorated SNT
arrays, most likely because the Ti(OH)4 precursor solution flowed freely into the
array through the open ends of the NTs in the DNT case but not in the SNT case.
The sNP@DNT-based DSC exhibited a better PCE (10%) compared to the sNP@SNT-based
DSCs (6.8%) because the electrolyte solution flow was not restricted, direct
electron transport though the NT arrays was possible, the electrical connection
at the interface between the NT array and the TiO2 NP interlayer was good, and
the array provided efficient light harvesting.
PMID- 25136741
TI - Discovery of a chemical modification by citric acid in a recombinant monoclonal
antibody.
AB - Recombinant therapeutic monoclonal antibodies exhibit a high degree of
heterogeneity that can arise from various post-translational modifications. The
formulation for a protein product is to maintain a specific pH and to minimize
further modifications. Generally Recognized as Safe (GRAS), citric acid is
commonly used for formulation to maintain a pH at a range between 3 and 6 and is
generally considered chemically inert. However, as we reported herein, citric
acid covalently modified a recombinant monoclonal antibody (IgG1) in a
phosphate/citrate-buffered formulation at pH 5.2 and led to the formation of so
called "acidic species" that showed mass increases of 174 and 156 Da,
respectively. Peptide mapping revealed that the modification occurred at the N
terminus of the light chain. Three additional antibodies also showed the same
modification but displayed different susceptibilities of the N-termini of the
light chain, heavy chain, or both. Thus, ostensibly unreactive excipients under
certain conditions may increase heterogeneity and acidic species in formulated
recombinant monoclonal antibodies. By analogy, other molecules (e.g., succinic
acid) with two or more carboxylic acid groups and capable of forming an anhydride
may exhibit similar reactivities. Altogether, our findings again reminded us that
it is prudent to consider formulations as a potential source for chemical
modifications and product heterogeneity.
PMID- 25136744
TI - Oxidation of bromophenols and formation of brominated polymeric products of
concern during water treatment with potassium permanganate.
AB - The extensive use of bromophenols (BrPs) in industrial products leads to their
occurrence in freshwater environments. This study explored the oxidation kinetics
of several BrPs (i.e., 2-BrP, 3-BrP, 4-BrP, 2,4-diBrP, and 2,6-diBrP) and
potential formation of brominated polymeric products of concern during water
treatment with potassium permanganate [Mn(VII)]. These BrPs exhibited appreciable
reactivity toward Mn(VII) with the maxima of second-order rate constants
(kMn(VII)) at pH near their pKa values, producing bell-shaped pH-rate profiles.
The unusual pH-dependency of kMn(VII) was reasonably explained by a tentative
reaction model, where the formation of an intermediate between Mn(VII) and
dissociated BrP was likely involved. A novel and powerful precursor ion scan
(PIS) approach was used for selective detection of brominated oxidation products
by liquid chromatography/electrospray ionization-triple quadrupole mass
spectrometry. Results showed that brominated dimeric products such as
hydroxylated polybrominated diphenyl ethers (OH-PBDEs) and hydroxylated
polybrominated biphenyls (OH-PBBs) were readily produced. For instance, 2'-OH-BDE
68, one of the most naturally abundant OH-PBDEs, could be formed at a relatively
high yield possibly via the coupling between bromophenoxyl radicals generated
from the one-electron oxidation of 2,4-diBrP by Mn(VII). Given the altered or
enhanced toxicological effects of these brominated polymeric products compared to
the BrP precursors, it is important to better understand their reactivity and
fate before Mn(VII) is applied by water utilities for the oxidative treatment of
BrP-containing waters.
PMID- 25136745
TI - Stimulation of cannabinoid receptors by using Rubus coreanus extracts to control
osteoporosis in aged male rats.
AB - A substantial proportion of men with prostatic disease have an increased risk of
bone loss. In the present study, we investigated the effects of Rubus coreanus
Miquel (RCM) extracts on osteoporosis that occurs with N-methyl-N-nitrosourea
(MNU)-induced prostatic hyperplasia. The rats used in this study were categorized
into groups of healthy controls, rats treated with MNU, and rats treated with MNU
and RCM. The rats were sacrificed after 10 weeks of RCM treatment, after which
ultrasonography, serum biochemical tests, histopathological examinations,
immunohistochemical analysis, and semi-quantitative reverse-transcription
polymerase chain reaction analysis were performed. There were no marked
differences in body weight gain and the size and weight of the prostate gland
between the MNU group and the MNU and RCM group. However, treatment with RCM
inhibited osteoclastic osteolysis and reduced dysplastic progress in the prostate
gland, as observed by histopathological evaluation and by analyzing changes in
the levels of bone regulatory factors. In addition, the group treated with MNU
and RCM had higher expression levels of cannabinoid receptors-1, -2, and
osteoprotegerin. These results indicate that the anti-osteoporotic effect of RCM
in prostatic hyperplasia is attributable to the cannabinoid receptor-related
upregulation of osteoblastogenesis and inhibition of prostatic hyperplasia. The
results of the present study suggest that treatment with RCM may benefit
osteoporotic patients with prostatic disease by simultaneously altering the
activation of osteoblasts and osteoclasts.
PMID- 25136746
TI - Additional correction of OAB symptoms by two anti-muscarinics for men over 50
years old with residual symptoms of moderate prostatic obstruction after
treatment with Tamsulosin.
AB - OBJECTIVES: To study the effectiveness and safety of combined standard-dosed
Solifenacin and Trospium for management of symptoms of overactive bladder (OAB)
in elderly patients after the treatment with Tamsulosin. PATIENTS AND METHODS: A
total of 417 men over 50 years of age (average age 57.9 (8.3)) with diagnosed
prostatic obstruction (score 8-19 according to I-PSS), who had not taken
Tamsulosin before, were enrolled in the study. I-PSS questionnaire (from 8 to 19
moderate) and Awareness Tool questionnaire for evaluating OAB symptoms (total
score for OAB symptoms over 8) were used at the beginning and at the end of the
observation. Also, urodynamic parameters were examined. RESULT: Percentage of
patients with prevalent symptoms of obstruction of urethra decreases after the
treatment with Tamsulosin and then rises again (36.2%), but absolute number of
patients remains smaller than initial data. Percentage of patients with relative
prevalence of symptoms of overactive bladder slightly increases against
administration of Tamsulosin and reaches initial values at the time of
administration of anti-muscarinic drugs with absolute decrease in number of such
patients. CONCLUSION: Combination of Trospium and Solifenacin is an effective way
to manage residual symptoms of hyperactive bladder during treatment of early
obstruction of urinary bladder.
PMID- 25136747
TI - Routine screening for postnatal depression in a public health family service
unit: a retrospective study of self-excluding women.
AB - At this time, there is limited scientific knowledge about women who exclude
themselves from screening programs for postnatal depression. In this
retrospective descriptive study, we have sought to investigate the socio
demographic and psycho-social factors of women who withdraw from PND screening of
their own accord. Study participants were 525 women attending antenatal classes
who later took part in institutional routine screening for PND at the Consultorio
Familiare Service of the National Health Service, Italy. The PND screening
program consisted of the completion of the postpartum depression predictors
inventory-revised and psychological well-being (PWB) questionnaires within eight
to nine months of pregnancy, and Edinburgh Postnatal Depression Scale, GHQ-12 and
PWB within six to eight weeks after childbirth. The Responders group was made up
of 346 subjects - 65.9% of the total sample - who completed the entire program of
screening for PND. The Non-Responders group, on the other hand, consisted of 179
subjects - 34.1% of the total sample - who, after childbirth, withdrew from the
screening program. Compared to the Responders group, the Non-Responders group
showed a greater number of subjects with marital dissatisfaction, and with
unemployment as a stressful event. Health professionals who detect marital
dissatisfaction and/or unemployment as a stressful event in pregnant women should
bear in mind that these individuals, besides being at high risk for depression
after delivery, will also tend to exclude themselves from screening for PND.
PMID- 25136748
TI - Successful transportation of precious cargo: becoming an expert neonatal
transport nurse.
PMID- 25136749
TI - Responding to traumatic birth: subgaleal hemorrhage, assessment, and management
during transport.
AB - Subgaleal hemorrhage is an uncommon but often fatal complication of a traumatic
birth. Careful assessment and monitoring of the infant following birth are
necessary to ensure prompt intervention, referral, and improved outcomes.
Additional care, planning, and communication are especially important in the
transport environment.
PMID- 25136750
TI - Family-centered care during acute neonatal transport.
AB - PURPOSE: To evaluate current transport team communication practices and identify
areas for improvement from the parents' perspective. We also sought to determine
whether parents perceived that they were active participants in the care of their
infants during the transport process, consistent with the concepts of providing
family-centered care (FCC). SUBJECTS: Purposeful sampling of mothers and fathers
(or maternally designated support person if the father was not involved) of 25
infants who were transported for acute care to a level III neonatal intensive
care unit (NICU) between October 1, 2012, and September 18, 2013. DESIGN: This
quality improvement project used quantitative and qualitative analysis of a
parent questionnaire. METHODS: Mothers and fathers (or the support person) of
transported infants were invited to complete a questionnaire consisting of yes/no
and open-ended questions within the first 2 weeks of their infants' transport to
a level III NICU. The questions were related to the communication and information
parents received and their ability to participate in the transport process.
RESULTS: Twenty-seven parents completed the questionnaire. Responses to yes/no
questions identified areas for improvement for the transport team. These included
providing parents the opportunity to view an informational video; ensuring that
mothers had the opportunity to provide colostrum or breast milk before transport;
and providing an explanation to parents about their role as active participants
in their infants' care. Responses to the open-ended questions indicated that
approximately 40% of parents felt they had received adequate information about
their infants' care during the transport and many parents (40%) cited separation
from their infants as very concerning and causing distress. More than one-third
(40%) of the parents specifically stated that at least 1 parent should accompany
the infant during the transport. One father in this sample had been able to
accompany his infant to the tertiary center. CONCLUSIONS: The integration of FCC
core concepts during an acute neonatal transport is important to parents. The
orientation of parents to FCC during the transport process may facilitate
communication and help them become active participants in their infants' care.
PMID- 25136751
TI - Therapeutic hypothermia on transport: providing safe and effective cooling
therapy as the link between birth hospital and the neonatal intensive care unit.
AB - Therapeutic hypothermia as a neuroprotective strategy in neonates is an
established standard of care for infants with hypoxic-ischemic encephalopathy
(HIE) in tertiary care neonatal intensive care units (NICUs). To maximize the
neuroprotective effect in infants with HIE, hypothermia is initiated as soon as
possible after birth. Many infants who would benefit from therapeutic hypothermia
are not born at centers that have intensive care units or offer therapeutic
hypothermia and are thus transported to a tertiary care center with a NICU,
offering specialty services of therapeutic hypothermia and pediatric neurology.
The neonatal transport team plays a significant role in the management of these
critically ill infants. Clinical research provides data for safe and effective
management of these infants during therapeutic hypothermia in the NICU; however,
there are no evidence-based clinical guidelines for management before and during
transport. The establishment of evidence-based guidelines for cooling before and
during transport will facilitate early recognition of infants who would benefit
from therapeutic hypothermia therapy, and decrease delay in initiation of
therapy. Careful assessment, monitoring, and intervention by the transport team
are critical to provide appropriate care and ensure safe transport of these
infants.
PMID- 25136752
TI - Managing common neonatal respiratory conditions during transport.
AB - As neonatal care in the tertiary setting advances, neonatal transport teams are
challenged with incorporating these innovations into their work environment. One
of the largest areas of advancement over the last decade involves respiratory
support and management. Many major respiratory treatments and the equipment
required have been adapted for transport, whereas others are not yet feasible.
This article reviews the history of respiratory management during neonatal
transport and discusses current methodologies and innovations in transport
respiratory management.
PMID- 25136754
TI - Bioactive anthraquinone derivatives from the mangrove-derived fungus Stemphylium
sp. 33231.
AB - Four new anthraquinone derivatives (1-4) and four new alterporriol-type
anthranoid dimers (14-17), along with 17 analogues, were isolated from the solid
rice fermentation of the fungus Stemphylium sp. 33231 obtained from the mangrove
Bruguiera sexangula var. rhynchopetala collected from the South China Sea. Their
structures were elucidated using comprehensive spectroscopic methods. The
absolute configurations of 1, 3, and 4 were determined by single-crystal X-ray
diffraction of their derivatives (1a, 3b, and 4a). The absolute configurations of
the chiral 17-19 were determined by comparing their CD spectra with 21. The
inhibitory activities of most of the compounds against seven terrestrial
pathogenic bacteria and two cancer cell lines were evaluated.
PMID- 25136755
TI - Blocked inverted indices for exact clustering of large chemical spaces.
AB - The calculation of pairwise compound similarities based on fingerprints is one of
the fundamental tasks in chemoinformatics. Methods for efficient calculation of
compound similarities are of the utmost importance for various applications like
similarity searching or library clustering. With the increasing size of public
compound databases, exact clustering of these databases is desirable, but often
computationally prohibitively expensive. We present an optimized inverted index
algorithm for the calculation of all pairwise similarities on 2D fingerprints of
a given data set. In contrast to other algorithms, it neither requires GPU
computing nor yields a stochastic approximation of the clustering. The algorithm
has been designed to work well with multicore architectures and shows excellent
parallel speedup. As an application example of this algorithm, we implemented a
deterministic clustering application, which has been designed to decompose
virtual libraries comprising tens of millions of compounds in a short time on
current hardware. Our results show that our implementation achieves more than 400
million Tanimoto similarity calculations per second on a common desktop CPU.
Deterministic clustering of the available chemical space thus can be done on
modern multicore machines within a few days.
PMID- 25136759
TI - Cyber safety for adolescent girls: bullying, harassment, sexting, pornography,
and solicitation.
AB - PURPOSE OF REVIEW: To examine cyber safety for adolescent girls, specifically
issues around the definition, measurement, prevalence, and impact of
cyberbullying, harassment, sexting, pornography, and solicitation. RECENT
FINDINGS: Despite some continuing disagreements about definition, especially
around cyberbullying and cyber harassment, and about measurement, it is clear
that a significant minority of adolescents have potentially or actually harmful
experiences on the Internet. There are important sex differences, and those
exploited by pornography are mainly women. On some measures, these dangers have
increased in recent years, although the extent can be exaggerated. The nature of
Internet grooming appears to be changing. Negative effects are well documented in
a range of domains, although more longitudinal studies are needed. Individual
coping strategies, family and school-based support, and legal actions, all have a
role to play in minimizing these dangers. SUMMARY: Cyber safety is an important
issue. More research and action is needed, and interventions need to be evaluated
for their effectiveness.
PMID- 25136758
TI - Addressing the instability of DNA nanostructures in tissue culture.
AB - DNA nanotechnology is an advanced technique that could contribute diagnostic,
therapeutic, and biomedical research devices to nanomedicine. Although such
devices are often developed and demonstrated using in vitro tissue culture
models, these conditions may not be compatible with DNA nanostructure integrity
and function. The purpose of this study was to characterize the sensitivity of 3D
DNA nanostructures produced via the origami method to the in vitro tissue culture
environment and identify solutions to prevent loss of nanostructure integrity. We
examined whether the physiological cation concentrations of cell culture medium
and the nucleases present in fetal bovine serum (FBS) used as a medium supplement
result in denaturation and digestion, respectively. DNA nanostructure
denaturation due to cation depletion was design- and time-dependent, with one of
four tested designs remaining intact after 24 h at 37 degrees C. Adjustment of
medium by addition of MgSO4 prevented denaturation. Digestion of nanostructures
by FBS nucleases in Mg(2+)-adjusted medium did not appear design-dependent and
became significant within 24 h and when medium was supplemented with greater than
5% FBS. We estimated that medium supplemented with 10% FBS contains greater than
256 U/L equivalent of DNase I activity in digestion of DNA nanostructures. Heat
inactivation at 75 degrees C and inclusion of actin protein in medium
inactivated and inhibited nuclease activity, respectively. We examined the impact
of medium adjustments on cell growth, viability, and phenotype. Adjustment of
Mg(2+) to 6 mM did not appear to have a detrimental impact on cells. Heat
inactivation was found to be incompatible with in vitro tissue culture, whereas
inclusion of actin had no observable effect on growth and viability. In two in
vitro assays, immune cell activation and nanoparticle endocytosis, we show that
using conditions compatible with cell phenotype and nanostructure integrity is
critical for obtaining reliable experimental data. Our study thus describes
considerations that are vital for researchers undertaking in vitro tissue culture
studies with DNA nanostructures and some potential solutions for ensuring that
nanostructure integrity and functions are maintained during experiments.
PMID- 25136760
TI - Teen pregnancy: an update.
AB - PURPOSE OF REVIEW: To provide clinicians with a review of recent research and
clinically applicable tools regarding teen pregnancy. RECENT FINDINGS: Teen
pregnancy rates have declined but still remain a significant problem in the USA.
Teen pregnancy prevention was identified by Centers for Disease Control and
Prevention as one of its top six priorities, which is increasing research and
intervention data. Long-acting contraceptive methods are acceptable to teens and
have been shown to reduce teen birth rates. Pregnant teens need special attention
to counseling on pregnancy options and reducing risk during pregnancy with
regular prenatal care. Postpartum teens should be encouraged and supported to
breastfeed, monitored for depression, and have access to reliable contraception
to avoid repeat undesired pregnancy. SUMMARY: This review highlights important
issues for all providers caring for female adolescents and those who may
encounter teen pregnancy. Foremost prevention of teen pregnancy by comprehensive
sexual education and access to contraception is the priority. Educating patients
and healthcare providers about safety and efficacy of long-acting reversible
contraception is a good step to reducing undesired teen pregnancies. Rates of
postpartum depression are greater in adolescents than in adults, and adolescent
mothers need to be screened and monitored for depression. Strategies to avoid
another undesired pregnancy shortly after delivery should be implemented.
PMID- 25136761
TI - Role of apical support defect: correction in women undergoing vaginal prolapse
surgery.
AB - PURPOSE OF REVIEW: The aim was to review most recent literature and provide
updates in clinical management and surgical treatment of apical pelvic organ
prolapse. RECENT FINDINGS: In patients who decline surgical intervention, formal
referral to pelvic floor muscle training is beneficial over self-directed Kegel
exercises. Systematic reviews revealed that sacrocolpopexy has better long-term
outcomes than vaginal approaches. Uterosacral ligament suspension and
sacrospinous ligament suspension have equal efficacy at 1 year. These procedures
should be considered as acceptable alternatives to sacrocolpopexy. Two randomized
controlled trials have demonstrated equal efficacy between robotic and
laparoscopic sacrocolpopexy. SUMMARY: Minimally invasive sacrocolpopexy should be
considered the gold standard for apical prolapse, but these techniques are
associated with longer operating times and higher complication rates and longer
convalescence than nonmesh vaginal surgery. Surgeons must individualize surgical
technique for each patient and should consider a vaginal approach in patients who
do not desire laparotomy and are not candidates for minimally invasive surgery.
PMID- 25136762
TI - Patient perspective in health technology assessment of pharmaceuticals in
Finland.
AB - OBJECTIVES: The need to consider the patient perspective in health technology
assessments (HTA) has been widely recognized. In July 2012, the Finnish Medicines
Agency (Fimea) published a national recommendation for integrating the patient
perspective into the HTAs of pharmaceuticals. The aim of this study is to
describe the development of the recommendation for integrating the patient
perspective into the HTA process of pharmaceuticals in Finland. METHODS: The
development of the recommendation was based on a review of international
recommendations and experiences of patient and public involvement in HTA. The
draft recommendation was tested in two focus group discussions (n = 7 patients)
and three individual interviews among diabetes patients (type 1 or 2) using long
acting insulin treatment. The recommendation was open for public consultation in
April 2012 and revised according to the comments received. RESULTS: Patients will
be involved in multiple stages of Fimea's HTA process. The recommendation
includes step-by-step instructions on how to assess the patient perspective. The
main focus is on qualitative interviews, which will be conducted at the beginning
of the assessments to gain information, particularly on patient preferences and
values, including positive and negative outcomes important to patients and
ethical and social aspects of the medicine's use. CONCLUSIONS: The recommendation
will act as a tool to integrate patients' experiences, needs and preferences into
Fimea's HTAs of pharmaceuticals.
PMID- 25136763
TI - Anti-inflammatory effects of wild Irish mushroom extracts in RAW264.7 mouse
macrophage cells.
AB - Mushrooms and mushroom extracts have traditionally been used as therapies for a
wide variety of ailments, including allergy, arthritis, and other inflammatory
disorders. However, more evidence is required on the mechanism by which mushrooms
exert these effects. In the present study, the anti-inflammatory properties of
ethanol and hot water extracts prepared from 27 fungal samples collected between
October and November 2011 at various forest locations in the southwest of Ireland
were investigated using the lipopolysaccharide (LPS)-stimulated mouse macrophage
(RAW264.7 cells) model of inflammation. LPS-stimulated cells were incubated in
the presence of mushroom extracts at nontoxic concentrations for 24 h and the
production of interleukin-6 (IL-6) was quantified by ELISA. Seven ethanolic and
one hot water extract that decreased IL-6 production were selected for further
study. The extracts were then incubated with LPS-stimulated cells for 24 h and
the production of IL-6, tumor necrosis factor-alpha (TNF-alpha), and nitric oxide
(NO) was measured. Ethanolic extracts prepared from Russula mairei, Lactarius
blennius, Craterellus tubaeformis, Russula fellea, and Craterellus cornucopioides
demonstrated selective anti-inflammatory activity by decreasing the production of
NO and IL-6 but not TNF-alpha in LPS-stimulated RAW264.7 cells. These findings
support existing evidence of the anti-inflammatory potential of mushroom
extracts.
PMID- 25136764
TI - Nanoscale metal-organic frameworks for real-time intracellular pH sensing in live
cells.
AB - Real-time measurement of intracellular pH in live cells is of great importance
for understanding physiological/pathological processes and developing
intracellular drug delivery systems. We report here the first use of nanoscale
metal-organic frameworks (NMOFs) for intracellular pH sensing in live cells.
Fluorescein isothiocyanate (FITC) was covalently conjugated to a UiO NMOF to
afford F-UiO NMOFs with exceptionally high FITC loadings, efficient fluorescence,
and excellent ratiometric pH-sensing properties. Upon rapid and efficient
endocytosis, F-UiO remained structurally intact inside endosomes. Live cell
imaging studies revealed endo- and exocytosis of F-UiO and endosome acidification
in real time. Fluorescently labeled NMOFs thus represent a new class of
nanosensors for intracellular pH sensing and provide an excellent tool for
studying NMOF-cell interactions.
PMID- 25136766
TI - Effects of the steric hindrance of micropores in the hyper-cross-linked polymeric
adsorbent on the adsorption of p-nitroaniline in aqueous solution.
AB - A hyper-cross-linked polymeric adsorbent with "--CH2--phenol--CH2--" as the cross
linked bridge (denoted GQ-05), and another hyper-cross-linked polymeric adsorbent
with "--CH2--p-cresol--CH2--" as the cross-linked bridge (denoted GQ-03) were
synthesized to reveal the effect of the steric hindrance of micropores in the
hyper-cross-linked polymeric adsorbent on adsorption capacity and adsorption rate
of p-nitroaniline (PNA) from aqueous solution. The results of adsorption kinetics
indicated the order of the adsorption rate GQ-05>GQ-03. The pseudo-first-order
rate equation could describe the entire adsorption process of PNA onto GQ-05
while the equation characterized the adsorption process of GQ-03 in two stages.
The order of the adsorption capacity GQ-05>GQ-03 was demonstrated by
thermodynamic analysis and dynamic adsorption. The steric hindrance of micropores
in the hyper-cross-linked polymeric adsorbent was a crucial factor for the order
of the adsorption capacity and adsorption rate.
PMID- 25136765
TI - On the possible role of macrofungi in the biogeochemical fate of uranium in
polluted forest soils.
AB - Interactions of macrofungi with U, Th, Pb and Ag were investigated in the former
ore mining district of Pribram, Czech Republic. Samples of saprotrophic (34
samples, 24 species) and ectomycorrhizal (38 samples, 26 species) macrofungi were
collected from a U-polluted Norway spruce plantation and tailings and analyzed
for metal content. In contrast to Ag, which was highly accumulated in fruit
bodies, concentrations of U generally did not exceed 3mg/kg which indicates a
very low uptake rate and efficient exclusion of U from macrofungi. In
ectomycorrhizal tips (mostly determined to species level by DNA sequencing), U
contents were practically identical with those of the non-mycorrhizal fine spruce
roots. These findings suggest a very limited role of macrofungi in uptake and
biotransformation of U in polluted forest soils. Furthermore, accumulation of U,
Th, Pb and Ag in macrofungal fruit-bodies apparently does not depend on total
content and chemical fractionation of these metals in soils (tested by the BCR
sequential extraction in this study).
PMID- 25136767
TI - A sweet new wave: structures and mechanisms of enzymes that digest
polysaccharides from marine algae.
AB - Marine algae contribute approximately half of the global primary production. The
large amounts of polysaccharides synthesized by these algae are degraded and
consumed by microbes that utilize carbohydrate-active enzymes (CAZymes), thus
creating one of the largest and most dynamic components of the Earth's carbon
cycle. Over the last decade, structural and functional characterizations of
marine CAZymes have revealed a diverse set of scaffolds and mechanisms that are
used to degrade agars, carrageenan, alginate and ulvan-polysaccharides from red,
brown and green seaweeds, respectively. The analysis of these CAZymes is not only
expanding our understanding of their functions but is enabling the enhanced
annotation of (meta)-genomic data sets, thus promoting an improved understanding
of microbes that drive this marine component of the carbon cycle. Furthermore,
this information is setting a foundation that will enable marine algae to be
harnessed as a novel resource for biorefineries. In this review, we cover the
most recent structural and functional analyses of marine CAZymes that are
specialized in the digestion of macro-algal polysaccharides.
PMID- 25136768
TI - Insulin-like growth factor-1 attenuates apoptosis and protects neurochemical
phenotypes of dorsal root ganglion neurons with paclitaxel-induced neurotoxicity
in vitro.
AB - Paclitaxel (PT)-induced neurotoxicity is a significant problem associated with
successful treatment of cancers. Insulin-like growth factor-1 (IGF-1) is a
neurotrophic factor and plays an important role in promoting axonal growth from
dorsal root ganglion (DRG) neurons. Whether IGF-1 has protective effects on
neurite growth, cell viability, neuronal apoptosis and neuronal phenotypes in DRG
neurons with PT-induced neurotoxicity is still unclear. In this study, primary
cultured rat DRG neurons were used to assess the effects of IGF-1 on DRG neurons
with PT-induced neurotoxicity. The results showed that PT exposure caused neurite
retraction in a dose-dependent manner. PT exposure caused a decrease of cell
viability and an increase in the ratio of apoptotic cells which could be reversed
by IGF-1. The percentage of calcitonin gene-related peptide immunoreactive (CGRP
IR) neurons and neurofilament (NF)-200-IR neurons, mRNA, and protein levels of
CGRP and NF-200 decreased significantly after treatment with PT. IGF-1
administration had protective effects on CGRP-IR neurons, but not on NF-200-IR
neurons. Either extracellular signal-regulated protein kinase (ERK1/2) inhibitor
PD98059 or phosphatidylinositol 3-kinase (PI3 K) inhibitor LY294002 blocked the
effect of IGF-1. The results imply that IGF-1 may attenuate apoptosis to improve
neuronal cell viability and promote neurite growth of DRG neurons with PT-induced
neurotoxicity. Moreover, these results support an important neuroprotective role
of exogenous IGF-1 on distinct subpopulations of DRG neurons which is responsible
for skin sensation. The effects of IGF-1 might be through ERK1/2 or PI3 K/Akt
signaling pathways. These findings provide experimental evidence for IGF-1
administration to alleviate neurotoxicity of distinct subpopulations of DRG
neurons induced by PT.
PMID- 25136770
TI - Early response to chemoradiotherapy for nasopharyngeal carcinoma treatment: Value
of dynamic contrast-enhanced 3.0 T MRI.
AB - PURPOSE: To prospectively evaluate the dynamic contrast-enhanced magnetic
resonance imaging (DCE-MRI) value for predicting early nasopharyngeal carcinoma
(NPC) chemoradiotherapy (CRT) response. MATERIALS AND METHODS: Forty-two patients
with advanced NPC were recruited and received three DCE-MRI exams before
treatment (Pre-Tx), as well as 3 days (Day 3-Tx) and 40 days (Day 40-Tx) after
chemotherapy initiation (two neoadjuvant chemotherapy cycles, NAC). We used DCE
Tool to measure primary tumor kinetic parameters (K(trans) , Kep , ve , and vp )
using the extended Tofts model. Kinetic parameters and corresponding changes were
compared between responders and nonresponders after NAC or CRT treatment using
Student's t or Mann-Whitney U tests. RESULTS: Response to two NAC cycles
correlated with short-term local control (P = 0.01). Compared to the nonresponder
group, the responder group presented with significantly larger DeltaK(trans) (0
3) , DeltaKep(0-3) , and Deltavp(0-3) values after NAC (P < 0.05). The complete
response group after CRT exhibited significantly lower K(trans) (Day 40-Tx) and
larger DeltaK(trans) (0-3) values than the residual group (P = 0.05). High
sensitivity (range: 74.1%-90%) and moderate-to-high specificity (range: 50%
84.3%) distinguished nonresponders from responders grouping after NAC or CRT,
with diagnostic efficiency ranging from 69.3%-88%. CONCLUSION: Our study showed
kinetic parameter changes earlier after chemotherapy were potential markers for
NPC patients receiving CRT therapy following NAC.
PMID- 25136771
TI - Biological risk among hospital housekeepers.
AB - Although not directly responsible for patient care, hospital housekeepers are
still susceptible to accidents with biological material. The objectives of this
study were to establish profile and frequency of accidents among hospital
housekeepers, describe behaviors pre- and postaccident, and risk factors. This
was a cross-sectional study with hospital housekeepers in Goiania, Brazil. Data
were obtained from interviews and vaccination records. The observations were as
follows: (1) participating workers: 94.3%; (2) incomplete hepatitis B
vaccination: 1 in 3; and (3) accident rate: 26.5%, mostly percutaneous with
hypodermic needles, and involved blood from an unknown source; roughly half
occurred during waste management. Upon review, length of service less than 5
years, completed hepatitis B vaccination, and had been tested for anti-HBs
(hepatitis B surface antigen) influenced frequency of accidents. These findings
suggest that improper disposal of waste appears to enhance the risk to hospital
housekeepers. All hospital workers should receive continued training with regard
to waste management.
PMID- 25136769
TI - Synthesis and characterization of oligonucleotides containing a nitrogen mustard
formamidopyrimidine monoadduct of deoxyguanosine.
AB - N(5)-Substituted formamidopyrimidine adducts have been observed from the reaction
of dGuo or DNA with aziridine containing electrophiles, including nitrogen
mustards. However, the role of substituted Fapy-dGuo adducts in the biological
response to nitrogen mustards and related species has not been extensively
explored. We have developed chemistry for the site-specific synthesis of
oligonucleotides containing an N(5)-nitrogen mustard Fapy-dGuo using the
phosphoramidite approach. The lesion was found to be a good substrate for
Escherichia coli endonuclease IV and formamidopyrimidine glycosylase.
PMID- 25136772
TI - Structural and mutational analysis of a monomeric and dimeric form of a single
domain antibody with implications for protein misfolding.
AB - Camelid single domain antibodies (sdAb) are known for their thermal stability and
reversible refolding. We have characterized an unusually stable sdAb recognizing
Staphylococcal enterotoxin B with one of the highest reported melting
temperatures (T(m) = 85 degrees C). Unexpectedly, ~10-20% of the protein formed a
dimer in solution. Three other cases where <20% of the sdAb dimerized have been
reported; however, this is the first report of both the monomeric and dimeric X
ray crystal structures. Concentration of the monomer did not lead to the
formation of new dimer suggesting a stable conformationally distinct species in a
fraction of the cytoplasmically expressed protein. Comparison of periplasmic and
cytoplasmic expression showed that the dimer was associated with cytoplasmic
expression. The disulfide bond was partially reduced in the WT protein purified
from the cytoplasm and the protein irreversibly unfolded. Periplasmic expression
produced monomeric protein with a fully formed disulfide bond and mostly
reversible refolding. Crystallization of a disulfide-bond free variant,
C22A/C99V, purified from the periplasm yielded a structure of a monomeric form,
while crystallization of C22A/C99V from the cytoplasm produced an asymmetric
dimer. In the dimer, a significant conformational asymmetry was found in the loop
residues of the edge beta-strands (S50-Y60) containing the highly variable
complementarity determining region, CDR2. Two dimeric assemblies were predicted
from the crystal packing. Mutation of a residue at one of the interfaces, Y98A,
disrupted the dimer in solution. The pleomorphic homodimer may yield insight into
the stability of misfolded states and the importance of the conserved disulfide
bond in preventing their formation.
PMID- 25136774
TI - Inpatient and emergency service utilization in patients with idiopathic
intracranial hypertension.
AB - BACKGROUND: Many patients with idiopathic intracranial hypertension (IIH) are
diagnosed in the emergency department (ED) or visit the ED during the course of
their illness. We studied the use of inpatient and emergency services, determined
what procedures and tests were provided at those encounters, evaluated how these
variables changed over the study period and examined the coding validity of the
International Classification of Diseases (ICD)-9 code for IIH (348.2) for adult
patients seen in our affiliated EDs and inpatient services. METHODS:
Retrospective review of medical records over a 11-year period (2000-2011).
RESULTS: We were able to analyze 137 encounters from 51 patients. Sixty-eight
percent of encounters were to the ED and 40% of those patients were subsequently
admitted to the hospital. The most common symptoms were headaches (96%), vision
change (53%), and photophobia (27%). Recurrent symptoms accounted for 43% of
encounters, followed by surgical complications (26%) and initial presentation
(12%). Four patients (25% of the patients who received a diagnosis in the ED)
were misdiagnosed at their initial presentation and correctly diagnosed on a
subsequent ED visit. The number of ED visits more than doubled over the study
period. The ICD-9 code had a low positive predictive value (55%) for identifying
patients with IIH. CONCLUSIONS: The ED was commonly used by patients with IIH,
with a mean of 2.7 visits per patient. The rate of a missed diagnosis was similar
to another published series and is concerning for potentially permanent visual
loss in undiagnosed patients. In our experience, the ICD-9 code vastly
overestimated the number of ED and inpatient encounters attributable to IIH. This
has important implications for research studies, particularly those relying on
national inpatient databases.
PMID- 25136775
TI - Idiopathic opticochiasmatic arachnoiditis.
AB - : A critical review of the literature indicates that idiopathic opticochiasmatic
arachnoiditis, once considered an important consideration in patients with
otherwise unexplained optic atrophy, is not a valid disease entity.
PMID- 25136773
TI - Genistein disrupts glucocorticoid receptor signaling in human uterine endometrial
Ishikawa cells.
AB - BACKGROUND: The link between environmental estrogen exposure and defects in the
female reproductive tract is well established. The phytoestrogen genistein is
able to modulate uterine estrogen receptor (ER) activity, and dietary exposure is
associated with uterine pathologies. Regulation of stress and immune functions by
the glucocorticoid receptor (GR) is also an integral part of maintaining
reproductive tract function; disruption of GR signaling by genistein may also
have a role in the adverse effects of genistein. OBJECTIVE: We evaluated the
transcriptional response to genistein in Ishikawa cells and investigated the
effects of genistein on GR-mediated target genes. METHODS: We used Ishikawa cells
as a model system to identify novel targets of genistein and the synthetic
glucocorticoid dexamethasone through whole genome microarray analysis. Common
gene targets were defined and response patterns verified by quantitative real
time reverse-transcription polymerase chain reaction. The mechanism of
transcriptional antagonism was determined for select genes. RESULTS: Genistein
regulated numerous genes in Ishikawa cells independently of estradiol, and the
response to coadministration of genistein and dexamethasone was unique compared
with the response to either estradiol or dexamethasone alone. Furthermore,
genistein altered glucocorticoid regulation of GR target genes. In a select set
of genes, co-regulation by dexamethasone and genistein was found to require both
GR and ERalpha signaling, respectively. CONCLUSIONS: Using Ishikawa cells, we
observed that exposure to genistein resulted in distinct changes in gene
expression and unique differences in the GR transcriptome.
PMID- 25136776
TI - Sorafenib regulating ERK signals pathway in gastric cancer cell.
AB - The involvement of ERK signals in gastric carcinoma was investigated using
Western blot, MTT, and flow cytometric analysis in cultured cells SGC7901.
Results showed that treatment of sorafenib potently inhibited gastric SGC7901
cells proliferation, migration, invasion as well as promoted apoptosis. Treatment
of sorafenib significantly decreased phosphorylation activation of ERK protein in
a dose-dependent manner. Treatment of sorafenib still significantly increased
caspase-3, bax, cyt-c protein expression and decreased bcl-2 protein in a dose
dependent manner. Our study confirms that ERK signals pathway is closely
associated with development of gastric cancer. Deactivation of phosphorylation of
ERK protein is one of the mechanisms of sorafenib inhibiting gastric cancer.
PMID- 25136777
TI - Integrated biomarker responses in zebrafish exposed to sulfonamides.
AB - Dispersed pharmaceuticals such as sulfonamides pose a threat to aquatic
ecosystems. We evaluated potential biomarkers of sulfonamide exposure using an
extended zebrafish (Danio rerio) toxicity test. The tested sulfonamides induced
obvious effects on spontaneous swimming activity and heartbeat rate in zebrafish.
Glutathione S-transferase (GST) and malondialdehyde (MDA) were examined to
reflect the biomarker response of zebrafish exposed to three sulfonamides
(sulfamethoxazole, sulfadiazine (SDZ) and sulfadimidine). Both GST and MDA showed
time-dependent responses to sulfonamide exposure. GST activity was significantly
increased after exposure to sulfonamides for 3 days, while MDA concentration
reached a maximum during the first day and then declined. These results suggest
that MDA may be a more sensitive biomarker of sulfonamide toxicity than GST.
These investigations demonstrated that SDZ was a typical inducer of metabolic
enzymes, suggesting that it poses a potential ecotoxicological risk to aquatic
ecosystems.
PMID- 25136778
TI - Endothelium-dependent and -independent vasorelaxant actions and mechanisms
induced by total flavonoids of Elsholtzia splendens in rat aortas.
AB - Elsholtzia splendens (ES) is, rich in flavonoids, used to repair copper
contaminated soil in China, which has been reported to benefit cardiovascular
systems as folk medicine. However, few direct evidences have been found to
clarify the vasorelaxation effect of total flavonoids of ES (TFES). The
vasoactive effect of TFES and its underlying mechanisms in rat thoracic aortas
were investigated using the organ bath system. TFES (5-200mg/L) caused a
concentration-dependent vasorelaxation in endothelium-intact rings, which was not
abolished but significantly reduced by the removal of endothelium. The nitric
oxide synthase (NOS) inhibitor N(omega)-nitro-l-arginine methyl ester (100MUM)
and the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,2-alpha]quinoxalin-1
one (30MUM) significantly blocked the endothelium-dependent vasorelaxation of
TFES. Meanwhile, NOS activity in endothelium-intact aortas was concentration
dependently elevated by TFES. However, indomethacin (10MUM) did not affect TFES
induced vasorelaxation. Endothelium-independent vasorelaxation of TFES was
significantly attenuated by KATP channel blocker glibenclamide. The accumulative
Ca(2+)-induced contraction in endothelium-denuded aortic rings primed with KCl or
phenylephrine was markedly weakened by TFES. These results revealed that the
NOS/NO/cGMP pathway is likely involved in the endothelium-dependent
vasorelaxation induced by TFES, while activating KATP channel, inhibiting
intracellular Ca(2+) release, blocking Ca(2+) channels and decreasing Ca(2+)
influx into vascular smooth muscle cells might contribute to the endothelium
independent vasorelaxation conferred by TFES.
PMID- 25136779
TI - All-trans-retinoid acid (ATRA) suppresses chondrogenesis of rat primary hind limb
bud mesenchymal cells by downregulating p63 and cartilage-specific molecules.
AB - P63 null mice have no or truncated limbs and mutations in human p63 cause several
skeletal syndromes that also show limb and digit abnormalities, suggesting its
essential role in bone development. In the current study, we investigated the
effect of ATRA on chondrogenesis using mesenchymal cells from rat hind limb bud
and further examined the mRNA and protein expression of Sox9 and Col2a1 and p63
in rat hind limb bud cells. Limb buds were isolated from embryos from euthanized
female rats. Growth of hind limb bud mesenchymal cells was determined by the 3
(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assays. Formation of
cartilage nodules was examined by Alcian blue-nuclear fast red staining. The
expression of Sox9, Col2al and p63 was determined by Real-time RT-PCR and
immunoblotting assays, respectively. Our MTT assays revealed that ATRA at 1 and
10MUM significantly suppressed the growth of mesenchymal cells from rat hind limb
bud at 24 and 48h (P<0.01 vs. controls). Alcian blue staining further showed that
ATRA caused a significant dose-dependent reduction in the area of cartilage
nodules (P<0.05 in all vs. controls). At 1MUM ATRA, the area of cartilage nodules
from hind limb bud cells was reduced to 0.05+/-0.03mm from 0.15+/-0.01mm in
controls. Real-time RT-PCR assays further indicated that 1 and 10MUM ATRA
markedly reduced the mRNA expression of Sox9, Col2al and p63 in hind limb bud
cells (P<0.05 in all vs. controls). In addition, ATRA time-dependently inhibits
the mRNA expression of p63, Sox9 and Col2al. Western blotting assays additionally
showed that ATRA dose-dependently reduced the expression of Sox9, Col2al and p63
(P<0.05 in all vs. controls). Together, our results suggest that ATRA suppresses
chondrogenesis by modulating the expression of Sox9, Col2al and p63 in primary
hind limb bud mesenchymal cells.
PMID- 25136780
TI - Macrophage-derived chemokine (CCL22) is a novel mediator of lung inflammation
following hemorrhage and resuscitation.
AB - Resuscitation of patients after hemorrhage often results in pulmonary
inflammation and places them at risk for the development of acute respiratory
distress syndrome. Our previous data indicate that macrophage-derived chemokine
(MDC/CCL22) is elevated after resuscitation, but its direct role in this
inflammatory response is unknown. Macrophage-derived chemokine signaling through
the C-C chemokine receptor type 4 (CCR4) is implicated in other pulmonary
proinflammatory conditions, leading us to hypothesize that MDC may also play a
role in the pathogenesis of lung inflammation following hemorrhage and
resuscitation. To test this, C57BL/6 mice underwent pressure-controlled
hemorrhage followed by resuscitation with lactated Ringer's solution. Pulmonary
inflammation and inflammatory cell recruitment were analyzed with histological
staining, and serum- and tissue-level cytokines were measured by enzyme-linked
immunosorbent assay. Pulmonary inflammation and cell recruitment following
hemorrhage and resuscitation were associated with systemic MDC levels. Inhibition
of MDC via injection of a specific neutralizing antibody prior to hemorrhage and
resuscitation significantly reduced pulmonary levels of the chemotactic cytokines
keratinocyte-derived chemokine and macrophage inflammatory proteins 2 and 1alpha,
as well as inflammatory cell recruitment to the lungs. Intravenous administration
of recombinant MDC prior to resuscitation augmented pulmonary inflammation and
cell recruitment. Histological evaluation revealed the expression of CCR4 within
the bronchial epithelium, and in vitro treatment of activated bronchial
epithelial cells with MDC resulted in production and secretion of neutrophil
chemokines. The present study identifies MDC as a novel mediator of lung
inflammation after hemorrhage and resuscitation. Macrophage-derived chemokine
neutralization may provide a therapeutic strategy to mitigate this inflammatory
response.
PMID- 25136783
TI - Screening for hyperuricaemia and gout: a perspective and research agenda.
AB - The goal of a screening programme is to reduce an adverse health outcome in a
defined population. Screening can be undertaken at several stages throughout the
disease course: before the onset of disease, early in the course of the disease,
or in established disease (for complications). In the setting of asymptomatic
hyperuricaemia and gout, the aim of screening would be to identify those
individuals with hyperuricaemia and therefore at risk of gout, with the aim of
introducing interventions to prevent the onset of gout. Herein we consider the
concepts of screening for hyperuricaemia and gout, potential screening methods,
and target populations that might benefit from such an approach.
PMID- 25136782
TI - Paraneoplastic syndromes in rheumatology.
AB - For patients that present with musculoskeletal symptoms, diagnostic procedures
carried out by physicians and rheumatologists are primarily aimed at confirming
or excluding the occurrence of primary rheumatic diseases. Another important
trigger for musculoskeletal disease, however, is the presence of a tumour.
Careful clinical investigation and knowledge of the gestalt of musculoskeletal
syndromes related to respective tumour entities is of utmost importance for the
diagnosis of paraneoplastic rheumatic diseases such as hypertrophic
osteoarthropathy, paraneoplastic polyarthritis, RS3PE syndrome, palmar fasciitis
and polyarthritis, cancer-associated myositis and tumour-induced osteomalacia.
This places great responsibility on rheumatologists in diagnosing malignancies
and referring the patient for effective treatment. The selective influence of
tumours on musculoskeletal tissue is surprising and indicates that tumours alter
tissues such as the periosteum, synovial membrane, subcutaneous connective
tissue, fascia, muscles and bones by specific molecular processes. Some of the
underlying mechanisms have been unravelled, providing valuable information on the
physiologic and pathophysiologic roles of mediators such as vascular endothelial
growth factor and fibroblast growth factor 23.
PMID- 25136781
TI - Transforming growth factor beta--at the centre of systemic sclerosis.
AB - Transforming growth factor beta (TGF-beta) has long been implicated in fibrotic
diseases, including the multisystem fibrotic disease systemic sclerosis (SSc).
Expression of TGF-beta-regulated genes in fibrotic skin and lungs of patients
with SSc correlates with disease activity, which points to this cytokine as the
central mediator of pathogenesis. Patients with SSc often develop pulmonary
arterial hypertension (PAH), a particularly lethal complication caused by
vascular dysfunction. Several genetic diseases with vascular features related to
SSc, such as familial PAH and hereditary haemorrhagic telangiectasia, are caused
by mutations in the TGF-beta-sensing ALK-1 signalling pathway. These observations
suggest that increased TGF-beta signalling causes both vascular and fibrotic
features of SSc. The question of how latent TGF-beta becomes activated in local
SSc tissues is, therefore, central to the understanding of SSc. Both TGF-beta1
and TGF-beta3 can be activated by integrins alphavbeta6 and alphavbeta8, whose
upregulation in bronchial epithelial cells can activate TGF-beta in SSc lungs.
Other alphav integrins, thrombospondin-1 or altered TGF-beta sequestration by
matrix proteins might be important in other target tissues. How the immune system
triggers this process remains unclear, although links between inflammation and
TGF-beta activation are emerging. Together, these observations provide an
increasingly secure framework for understanding TGF-beta in SSc pathogenesis.
PMID- 25136784
TI - IL-6 biology: implications for clinical targeting in rheumatic disease.
AB - IL-6 has been linked to numerous diseases associated with inflammation, including
rheumatoid arthritis, inflammatory bowel disease, vasculitis and several types of
cancer. Moreover, IL-6 is important in the induction of hepatic acute-phase
proteins for the trafficking of acute and chronic inflammatory cells, the
differentiation of adaptive T-cell responses, and tissue regeneration and
homeostatic regulation. Studies have investigated IL-6 biology using cell-bound
IL-6 receptors expressed predominantly on hepatocytes and certain haematopoietic
cells versus activation mediated by IL-6 and soluble IL-6 receptors via a second
protein, gp130, which is expressed throughout the body. Advances in this research
elucidating the differential effects of IL-6 activation provide important
insights into the role of IL-6 in health and disease, as well as its potential as
a therapeutic target. Knowledge of the basic biology of IL-6 and its signalling
pathways can better inform both the research agenda for IL-6-based targeted
therapies as well as the clinical use of strategies affecting IL-6-mediated
inflammation. This Review covers novel, emerging aspects of the biology of IL-6,
which might lead to more specific blockade of IL-6 signalling without
compromising the protective function of this cytokine in the body's defence
against infections.
PMID- 25136787
TI - A simplified coulometric method for multi-sample measurements of total dissolved
inorganic carbon concentration in marine waters.
AB - A new system requiring greatly reduced operator intervention has been developed
for the determination of dissolved inorganic carbon concentration in marine
waters. Based on a coulometric method, the system has an accuracy and precision
comparable to more complex and expensive methods currently employed. A syringe
pump equipped with a 12-port distribution valve is used to precisely dispense an
acid solution and sample into a gas stripper. The system can autonomously measure
eight discrete samples in duplicate or triplicate with no operator input. The
best precision (%RSD) obtained was 0.022% (n = 14) or less than +/-1.0 MUmol kg(
1). The system is calibrated against a certified reference material (CRM).
Average offset from the CRM was 1.2 MUmol kg(-1). Sample throughput was 4 samples
per h. Carryover effects are negligible but field sample analyses suggest that
prefiltering may be necessary in highly turbid waters.
PMID- 25136786
TI - The role of genetics and epigenetics in the pathogenesis of systemic sclerosis.
AB - Systemic sclerosis (SSc) is a complex autoimmune disease of unclear aetiology. A
multitude of genetic studies, ranging from candidate-gene studies to genome-wide
association studies, have identified a large number of genetic susceptibility
factors for SSc and its clinical phenotypes, but the contribution of these
factors to disease susceptibility is only modest. However, in an endeavour to
explore how the environment might affect genetic susceptibility, epigenetic
research into SSc is rapidly expanding. Orchestrated by environmental factors,
epigenetic modifications can drive genetically predisposed individuals to develop
autoimmunity, and are thought to represent the crossroads between the environment
and genetics in SSc. Therefore, in addition to providing a comprehensive
description of the current understanding of genetic susceptibility underlying
SSc, this Review describes the involvement of epigenetic phenomena, including DNA
methylation patterns, histone modifications and microRNAs, in SSc.
PMID- 25136785
TI - Improving cardiovascular and renal outcomes in gout: what should we target?
AB - Epidemiological and experimental studies have shown that hyperuricaemia and gout
are intricately linked with hypertension, metabolic syndrome, chronic kidney
disease and cardiovascular disease. A number of studies suggest that
hyperuricaemia and gout are independent risk factors for the development of these
conditions and that these conditions account, in part, for the increased
mortality rate of patients with gout. In this Review, we first discuss the links
between hyperuricaemia, gout and these comorbidities, and present the mechanisms
by which uric acid production and gout might favour the development of
cardiovascular and renal diseases. We then emphasize the potential benefit of
urate-lowering therapies on cardiovascular and renal outcomes in patients with
hyperuricaemia. The mechanisms that link elevated serum uric acid levels and gout
with these comorbidities seem to be multifactorial, implicating low-grade
systemic inflammation and xanthine oxidase (XO) activity, as well as the
deleterious effects of hyperuricaemia itself. Patients with asymptomatic
hyperuricaemia should be treated by nonpharmacological means to lower their SUA
levels. In patients with gout, long-term pharmacological inhibition of XO is a
treatment strategy that might also reduce cardiovascular and renal comorbidities,
because of its dual effect of lowering SUA levels as well as reducing free
radical production during uric acid formation.
PMID- 25136788
TI - L. monocytogenes in a cheese processing facility: Learning from contamination
scenarios over three years of sampling.
AB - The aim of this study was to analyze the changing patterns of Listeria
monocytogenes contamination in a cheese processing facility manufacturing a wide
range of ready-to-eat products. Characterization of L. monocytogenes isolates
included genotyping by pulsed-field gel electrophoresis (PFGE) and multi-locus
sequence typing (MLST). Disinfectant-susceptibility tests and the assessment of
L. monocytogenes survival in fresh cheese were also conducted. During the
sampling period between 2010 and 2013, a total of 1284 environmental samples were
investigated. Overall occurrence rates of Listeria spp. and L. monocytogenes were
21.9% and 19.5%, respectively. Identical L. monocytogenes genotypes were found in
the food processing environment (FPE), raw materials and in products.
Interventions after the sampling events changed contamination scenarios
substantially. The high diversity of globally, widely distributed L.
monocytogenes genotypes was reduced by identifying the major sources of
contamination. Although susceptible to a broad range of disinfectants and
cleaners, one dominant L. monocytogenes sequence type (ST) 5 could not be
eradicated from drains and floors. Significantly, intense humidity and steam
could be observed in all rooms and water residues were visible on floors due to
increased cleaning strategies. This could explain the high L. monocytogenes
contamination of the FPE (drains, shoes and floors) throughout the study (15.8%).
The outcome of a challenge experiment in fresh cheese showed that L.
monocytogenes could survive after 14days of storage at insufficient cooling
temperatures (8 and 16 degrees C). All efforts to reduce L. monocytogenes
environmental contamination eventually led to a transition from dynamic to stable
contamination scenarios. Consequently, implementation of systematic environmental
monitoring via in-house systems should either aim for total avoidance of FPE
colonization, or emphasize a first reduction of L. monocytogenes to sites where
contamination of the processed product is unlikely. Drying of surfaces after
cleaning is highly recommended to facilitate the L. monocytogenes eradication.
PMID- 25136789
TI - The influence of subminimal inhibitory concentrations of benzalkonium chloride on
biofilm formation by Listeria monocytogenes.
AB - Disinfectants, such as benzalkonium chloride (BAC), are commonly used to control
Listeria monocytogenes and other pathogens in food processing plants. Prior
studies have demonstrated that the resistance to BAC of L. monocytogenes was
associated with the prolonged survival of three strains of molecular serotype
1/2a in an Iberian pork processing plant. Because survival in such environments
is related to biofilm formation, we hypothesised that the influence of BAC on the
biofilm formation potential of L. monocytogenes might differ between BAC
resistant strains (BAC-R, MIC>=10mg/L) and BAC-sensitive strains (BAC-S,
MIC<=2.5mg/L). To evaluate this possibility, three BAC-R strains and eight BAC-S
strains, which represented all of the molecular serotype 1/2a strains detected in
the sampled plant, were compared. Biofilm production was measured using the
crystal violet staining method in 96-well microtitre plates. The BAC-R strains
produced significantly (p<0.05) less biofilm than the BAC-S in the absence of
BAC, independent of the rate of planktonic growth. In contrast, when the biofilm
values were measured in the presence of BAC, one BAC-R strain (S10-1) was able to
form biofilm at 5mg/L of BAC, which prevented biofilm formation among the rest of
the strains. A genetic determinant of BAC resistance recently described in L.
monocytogenes (Tn6188) was detected in S10-1. When a BAC-S strain and its
spontaneous mutant BAC-R derivative were compared, resistance to BAC led to
biofilm formation at 5mg/L of BAC and to a significant (p<0.05) stimulation of
biofilm formation at 1.25mg/L of BAC, which significantly (p<0.05) reduced the
biofilm level in the parent BAC-S strain. Our results suggest that the effect of
subminimal inhibitory concentrations of BAC on biofilm production by L.
monocytogenes might differ between strains with different MICs and even between
resistant strains with similar MICs but different genetic determinants of BAC
resistance. For BAC-R strains similar to S10-1, subminimal inhibitory BAC may
represent an advantage, compensating for the weak biofilm formation level that
might be associated with resistance. Biofilm formation in the presence of
increased subminimal inhibitory concentrations of the disinfectant may represent
an important attribute among certain resistant and persistent strains of L.
monocytogenes.
PMID- 25136790
TI - Tonic water-induced generalized bullous fixed eruption.
PMID- 25136792
TI - Low carrier density epitaxial graphene devices on SiC.
AB - The transport characteristics of graphene devices with low n- or p-type carrier
density (~10(10) -10(11) cm(-2) ), fabricated using a new process that results in
minimal organic surface residues, are reported. The p-type molecular doping
responsible for the low carrier densities is initiated by aqua regia. The
resulting devices exhibit highly developed nu = 2 quantized Hall resistance
plateaus at magnetic field strengths of less than 4 T.
PMID- 25136791
TI - Rationale and study design of the REM-HF study: remote management of heart
failure using implanted devices and formalized follow-up procedures.
AB - AIMS: We wish to assess the clinical and cost-effectiveness of remote monitoring
of heart failure patients with cardiac implanted electronic devices. METHODS: REM
HF is a multicentre, randomized, non-blinded, parallel trial designed to compare
weekly remote monitoring-driven management with usual care for patients with
cardiac implanted electronic devices (ICD, CRT-D, or CRT-P). The trial is event
driven, and the final analysis will be performed when 546 events have been
observed or the study is terminated at the interim analysis. We have randomized
1650 patients to be followed up for a minimum of 2 years. Patients will remain in
the trial up to study termination. The first patient was randomized in September
2011 and the study is expected to complete in early 2016. The primary combined
endpoint is time to first event of all-cause death or unplanned hospitalization
for cardiovascular reasons. An economic evaluation will be performed, estimating
the cost per quality-adjusted life year, with direct costs estimated from the
National Health Service perspective and quality of life assessed by the EQ-5D,
Short-Form 12, and Kansas City Cardiomyopathy Questionnaires. The study design
has been informed by a feasibility study. CONCLUSION: REM-HF is a multicentre
randomized study that will provide important data on the effect of remote
monitoring-driven management of implanted cardiac devices on morbidity and
mortality, as well as the cost-effectiveness of this approach.
PMID- 25136793
TI - The perception of materials through oral sensation.
AB - This paper presents the results of a multimodal study of oral perception
conducted with a set of material samples made from metals, polymers and woods, in
which both the somatosensory and taste factors were examined. A multidimensional
scaling analysis coupled with subjective attribute ratings was performed to
assess these factors both qualitatively and quantitatively. The perceptual
somatosensory factors of warmth, hardness and roughness dominated over the basic
taste factors, and roughness was observed to be a less significant sensation
compared to touch-only experiments. The perceptual somatosensory ratings were
compared directly with physical property data in order to assess the correlation
between the perceived properties and measured physical properties. In each case,
a strong correlation was observed, suggesting that physical properties may be
useful in industrial design for predicting oral perception.
PMID- 25136795
TI - Blood lead levels and associated factors among children in Guiyu of China: a
population-based study.
AB - OBJECTIVES: Children's health problems caused by the electronic waste (e-waste)
lead exposure in China remains. To assess children's blood lead levels (BLLs) in
Guiyu of China and investigate risk factors of children's elevated BLLs in Guiyu.
MATERIAL AND METHODS: 842 children under 11 years of age from Guiyu and Haojiang
were enrolled in this population-based study during 2011-2013. Participants
completed a lifestyle and residential environment questionnaire and their
physical growth indices were measured, and blood samples taken. Blood samples
were tested to assess BLLs. Children's BLLs between the two groups were compared
and factors associated with elevated BLLs among Guiyu children were analyzed by
group Lasso logistic regression model. RESULTS: Children living in Guiyu had
significant higher BLLs (7.06 ug/dL) than the quantity (5.89 ug/dL) of Haojiang
children (P<0.05). Subgroup analyses of BLLs exceeding 10 ug/dL showed the
proportion (24.80%) of high-level BLLs for Guiyu children was greater than that
(12.84%) in Haojiang (P<0.05). Boys had greater BLLs than girls, irrespectively
of areas (P<0.05). The number of e-waste piles or recycling workshops around the
house (odds ratio, 2.28; 95% confidence interval [CI], 1.37 to 3.87)
significantly contributed to the elevated BLLs of children in Guiyu, and girls
had less risk (odds ratio, 0.51; 95% CI, 0.31 to 0.83) of e-waste lead exposure
than boys. CONCLUSIONS: This analysis reinforces the importance of shifting e
waste recycling piles or workshops to non-populated areas as part of a
comprehensive response to e-waste lead exposure control in Guiyu. To correct the
problem of lead poisoning in children in Guiyu should be a long-term mission.
PMID- 25136797
TI - A systematic review of financial debt in adolescents and young adults:
prevalence, correlates and associations with crime.
AB - Financial debt in young people has increased in recent years. Because debt may
have severe consequences, and it may enhance criminal behavior, insight into the
prevalence and determinants of debt and its association with crime is important.
We conducted a systematic review and meta-analysis of 36 manuscripts to examine
the prevalence of financial debt (k = 23), correlates and risk factors of debt (k
= 16), and associations between debt and criminal behavior in adolescents and
young adults (k = 8). Findings revealed that the prevalence of debt is
substantial among young people; on average, 49% reported to have at least some
debt, 22% had financial problems. Older participants and ethnic minorities were
found to have higher levels of debt than younger and indigenous counterparts.
Females had more financial problems and higher student loans. Low self-esteem, a
pro-debt attitude (of young people and their parents), lack of perceived control
towards financial management, poor social functioning, financial stress and
external locus of control were found to have the strongest associations with
debt. Studies reported strong associations between debt and crime. Particularly,
strong associations were found between serious and persistent crime in young
people and later (young adult) debt or financial problems.
PMID- 25136798
TI - On the use of leaf spectral indices to assess water status and photosynthetic
limitations in Olea europaea L. during water-stress and recovery.
AB - Diffusional limitations to photosynthesis, relative water content (RWC), pigment
concentrations and their association with reflectance indices were studied in
olive (Olea europaea) saplings subjected to water-stress and re-watering. RWC
decreased sharply as drought progressed. Following rewatering, RWC gradually
increased to pre-stress values. Photosynthesis (A), stomatal conductance (gs),
mesophyll conductance (gm), total conductance (gt), photochemical reflectance
index (PRI), water index (WI) and relative depth index (RDI) closely followed
RWC. In contrast, carotenoid concentration, the carotenoid to chlorophyll ratio,
water content reflectance index (WCRI) and structural independent pigment index
(SIPI) showed an opposite trend to that of RWC. Photosynthesis scaled linearly
with leaf conductance to CO2; however, A measured under non-photorespiratory
conditions (A1%O2) was approximately two times greater than A measured at 21%
[O2], indicating that photorespiration likely increased in response to drought.
A1%O2 also significantly correlated with leaf conductance parameters. These
relationships were apparent in saturation type curves, indicating that under non
photorespiratory conditions, CO2 conductance was not the major limitations to A.
PRI was significant correlated with RWC. PRI was also very sensitive to pigment
concentrations and photosynthesis, and significantly tracked all CO2 conductance
parameters. WI, RDI and WCRI were all significantly correlated with RWC, and most
notably to leaf transpiration. Overall, PRI correlated more closely with
carotenoid concentration than SIPI; whereas WI tracked leaf transpiration more
effectively than RDI and WCRI. This study clearly demonstrates that PRI and WI
can be used for the fast detection of physiological traits of olive trees
subjected to water-stress.
PMID- 25136800
TI - Effects of infection by Trypanosoma cruzi and Trypanosoma rangeli on the
reproductive performance of the vector Rhodnius prolixus.
AB - The insect Rhodnius prolixus is responsible for the transmission of Trypanosoma
cruzi, which is the etiological agent of Chagas disease in areas of Central and
South America. Besides this, it can be infected by other trypanosomes such as
Trypanosoma rangeli. The effects of these parasites on vectors are poorly
understood and are often controversial so here we focussed on possible negative
effects of these parasites on the reproductive performance of R. prolixus,
specifically comparing infected and uninfected couples. While T. cruzi infection
did not delay pre-oviposition time of infected couples at either temperature
tested (25 and 30 degrees C) it did, at 25 degrees C, increase the e-value in the
second reproductive cycle, as well as hatching rates. Meanwhile, at 30 degrees C,
T. cruzi infection decreased the e-value of insects during the first cycle and
also the fertility of older insects. When couples were instead infected with T.
rangeli, pre-oviposition time was delayed, while reductions in the e-value and
hatching rate were observed in the second and third cycles. We conclude that both
T. cruzi and T. rangeli can impair reproductive performance of R. prolixus,
although for T. cruzi, this is dependent on rearing temperature and insect age.
We discuss these reproductive costs in terms of potential consequences on
triatomine behavior and survival.
PMID- 25136803
TI - An alteration in ATG16L1 stability in Crohn disease.
AB - Individuals who harbor a common coding polymorphism (Thr300Ala) within a
structurally unclassified region of ATG16L1 are at increased risk for the
development of Crohn disease. Recently, we reported on the generation and
characterization of knockin mice carrying the ATG16L1 T300A variant. We
demonstrate that multiple cell types from T300A knock-in mice exhibit reduced
selective autophagy, and we mechanistically link this phenotype with an increased
susceptibility of ATG16L1 T300A to CASP3- and CASP7-mediated cleavage. These
findings demonstrate how a single polymorphism can result in cell type- and
pathway-specific disruptions of selective autophagy and alterations in the
inflammatory milieu that can contribute to disease.
PMID- 25136801
TI - Regulation of autophagy and chloroquine sensitivity by oncogenic RAS in vitro is
context-dependent.
AB - Chloroquine (CQ) is an antimalarial drug and late-stage inhibitor of autophagy
currently FDA-approved for use in the treatment of rheumatoid arthritis and other
autoimmune diseases. Based primarily on its ability to inhibit autophagy, CQ and
its derivative, hydroxychloroquine, are currently being investigated as primary
or adjuvant therapy in multiple clinical trials for cancer treatment. Oncogenic
RAS has previously been shown to regulate autophagic flux, and cancers with high
incidence of RAS mutations, such as pancreatic cancer, have been described in the
literature as being particularly susceptible to CQ treatment, leading to the
hypothesis that oncogenic RAS makes cancer cells dependent on autophagy. This
autophagy "addiction" suggests that the mutation status of RAS in tumors could
identify patients who would be more likely to benefit from CQ therapy. Here we
show that RAS mutation status itself is unlikely to be beneficial in such a
patient selection because oncogenic RAS does not always promote autophagy
addiction. Moreover, oncogenic RAS can have opposite effects on both autophagic
flux and CQ sensitivity in different cells. Finally, for any given cell type, the
positive or negative effect of oncogenic RAS on autophagy does not necessarily
predict whether RAS will promote or inhibit CQ-mediated toxicity. Thus, although
our results confirm that different tumor cell lines display marked differences in
how they respond to autophagy inhibition, these differences can occur
irrespective of RAS mutation status and, in different contexts, can either
promote or reduce chloroquine sensitivity of tumor cells.
PMID- 25136802
TI - A role of autophagy in PTP4A3-driven cancer progression.
AB - Autophagy, a "self-eating" cellular process, has dual roles in promoting and
suppressing tumor growth, depending on cellular context. PTP4A3/PRL-3, a plasma
membrane and endosomal phosphatase, promotes multiple oncogenic processes
including cell proliferation, invasion, and cancer metastasis. In this study, we
demonstrate that PTP4A3 accumulates in autophagosomes upon inhibition of
autophagic degradation. Expression of PTP4A3 enhances PIK3C3-BECN1-dependent
autophagosome formation and accelerates LC3-I to LC3-II conversion in an ATG5
dependent manner. PTP4A3 overexpression also enhances the degradation of SQSTM1,
a key autophagy substrate. These functions of PTP4A3 are dependent on its
catalytic activity and prenylation-dependent membrane association. These results
suggest that PTP4A3 functions to promote canonical autophagy flux. Unexpectedly,
following autophagy activation, PTP4A3 serves as a novel autophagic substrate,
thereby establishing a negative feedback-loop that may be required to fine-tune
autophagy activity. Functionally, PTP4A3 utilizes the autophagy pathway to
promote cell growth, concomitant with the activation of AKT. Clinically, from the
largest ovarian cancer data set (GSE 9899, n = 285) available in GEO, high levels
of expression of both PTP4A3 and autophagy genes significantly predict poor
prognosis of ovarian cancer patients. These studies reveal a critical role of
autophagy in PTP4A3-driven cancer progression, suggesting that autophagy could be
a potential Achilles heel to block PTP4A3-mediated tumor progression in
stratified patients with high expression of both PTP4A3 and autophagy genes.
PMID- 25136806
TI - Insignificant medium-term vitamin D status change after 25-hydroxyvitamin D
testing in a large managed care population.
AB - OBJECTIVES: To examine the clinical utility of 25-hydroxyvitamin D (25(OH)D)
testing in achieving medium-term vitamin D (VD) sufficiency in a managed care
population. METHODS: Retrospective study of a continuously-enrolled patient
population in a 3-year period between 2011 and 2013. Primary outcome was VD
status at ~1 year after 25(OH)D testing. Patient demographics, comorbidities,
medications, and 25(OH)D test results were gathered from relevant databases and
multivariate logistic regression analysis used to study the risk factors of
persistent VD deficiency or insufficiency. RESULTS: Of 22,784 patients, 7533
(females 69.3%) did 14,563 25(OH)D tests, with an estimated cost of $582,520. Of
the 7533 patients, 1126 had another 25(OH)D test at 300-400 days after the first
one. Based on the two test results, 234 patients (20.8%) maintained sufficient
25(OH)D levels; 132 (11.7%) turned from VD-sufficient into VD-insufficient or
deficient; 538 (47.8%) remained VD-insufficient or -deficient, and only 222
(19.7%) improved to be VD-sufficient. Overall, only 8.0% more patients were VD
sufficient at ~1 year after 25(OH)D testing. Only younger age and higher BMI were
independent risk factors for persistent low 25(OH)D levels and high-dose VD use
was not associated with achieving VD sufficiency. CONCLUSIONS: 25(OH)D testing
only benefits a small portion of patients thus lacks clinical utility in
achieving VD sufficiency in the medium term but incurs a significant cost. A
practical strategy to treat VD deficiency or insufficiency is needed; without it,
25(OH)D testing adds little value to most patients' health and should be used
with discretion.
PMID- 25136805
TI - Transcriptome analysis of the oil-rich tea plant, Camellia oleifera, reveals
candidate genes related to lipid metabolism.
AB - BACKGROUND: Rapidly driven by the need for developing sustainable sources of
nutritionally important fatty acids and the rising concerns about environmental
impacts after using fossil oil, oil-plants have received increasing awareness
nowadays. As an important oil-rich plant in China, Camellia oleifera has played a
vital role in providing nutritional applications, biofuel productions and
chemical feedstocks. However, the lack of C. oleifera genome sequences and little
genetic information have largely hampered the urgent needs for efficient
utilization of the abundant germplasms towards modern breeding efforts of this
woody oil-plant. RESULTS: Here, using the 454 GS-FLX sequencing platform, we
generated approximately 600,000 RNA-Seq reads from four tissues of C. oleifera.
These reads were trimmed and assembled into 104,842 non-redundant putative
transcripts with a total length of ~38.9 Mb, representing more than 218-fold of
all the C. oleifera sequences currently deposited in the GenBank (as of March
2014). Based on the BLAST similarity searches, nearly 42.6% transcripts could be
annotated with known genes, conserved domains, or Gene Ontology (GO) terms.
Comparisons with the cultivated tea tree, C. sinensis, identified 3,022 pairs of
orthologs, of which 211 exhibited the evidence under positive selection. Pathway
analysis detected the majority of genes potentially related to lipid metabolism.
Evolutionary analysis of omega-6 fatty acid desaturase (FAD2) genes among 20 oil
plants unexpectedly suggests that a parallel evolution may occur between C.
oleifera and Olea oleifera. Additionally, more than 2,300 simple sequence repeats
(SSRs) and 20,200 single-nucleotide polymorphisms (SNPs) were detected in the C.
oleifera transcriptome. CONCLUSIONS: The generated transcriptome represents a
considerable increase in the number of sequences deposited in the public
databases, providing an unprecedented opportunity to discover all related-genes
associated with lipid metabolic pathway in C. oleifera. It will greatly enhance
the generation of new varieties of C. oleifera with increased yields and high
quality.
PMID- 25136807
TI - [Arthrogenic muscle inhibition after trauma - is there an age dependency of the
intensity of arthrogenic muscle inhibition?].
AB - Backround: Knee trauma with arthrogenic muscle inhibition (AMI) lead to muscle
weakness. The aim of this study was to analyse the intensity of AMI after
meniscus and cartilage injuries and to investigate the association between age,
BMI and severity of cartilage leasions with AMI. PATIENTS AND METHODS: 48
patients with meniscus or cartilage injury were preoperatively interviewed and
examined for isometric maximum force values of the extension muscles of the knee
joints. We analysed AMI as comparison of maximum isometric force values between
healthy and injured leg by use of Wilcoxon matched pairs test. Moreover a
regression analysis was done to assess the association between age, BMI and
severity of cartilage lesion with AMI. RESULTS: Trauma of the knee joint with
meniscus or cartilage injuries led to a 23.6 % reduction of maximum force values
of injured in comparison to healthy leg (460.1 +/- 223.6 N vs. 601.9 +/- 224.6 N,
P < 0,000001) in mean. Regression analysis did not show associations between age
(beta -2.645, P = 0.345), BMI (beta 2.268, P = 0.792) or severity of cartilage
damage (beta -13.527, P = 0.670) with AMI. CONCLUSIONS: Trauma of the knee joint
with meniscus or cartilage damage cause an AMI with 23.6 % force reduction. We
could not identify an association between age and AMI.
PMID- 25136804
TI - Abeta1-42 monomers or oligomers have different effects on autophagy and
apoptosis.
AB - The role of autophagy and its relationship with apoptosis in Alzheimer disease
(AD) pathogenesis is poorly understood. Disruption of autophagy leads to buildup
of incompletely digested substrates, amyloid-beta (Abeta) peptide accumulation in
vacuoles and cell death. Abeta, in turn, has been found to affect autophagy.
Thus, Abeta might be part of a loop in which it is both the substrate of altered
autophagy and its cause. Given the relevance of different soluble forms of Abeta1
42 in AD, we have investigated whether monomers and oligomers of the peptide have
a differential role in causing altered autophagy and cell death. Using
differentiated SK-N-BE neuroblastoma cells, we found that monomers hamper the
formation of the autophagic BCL2-BECN1/Beclin 1 complex and activate the
MAPK8/JNK1-MAPK9/JNK2 pathway phosphorylating BCL2. Monomers also inhibit
apoptosis and allow autophagy with intracellular accumulation of autophagosomes
and elevation of levels of BECN1 and LC3-II, resulting in an inhibition of
substrate degradation due to an inhibitory action on lysosomal activity.
Oligomers, in turn, favor the formation of the BCL2-BECN1 complex favoring
apoptosis. In addition, they cause a less profound increase in BECN1 and LC3-II
levels than monomers without affecting the autophagic flux. Thus, data presented
in this work show a link for autophagy and apoptosis with monomers and oligomers,
respectively. These studies are likely to help the design of novel disease
modifying therapies.
PMID- 25136808
TI - The response of human thermal sensation and its prediction to temperature step
change (cool-neutral-cool).
AB - This paper reports on studies of the effect of temperature step-change (between a
cool and a neutral environment) on human thermal sensation and skin temperature.
Experiments with three temperature conditions were carried out in a climate
chamber during the period in winter. Twelve subjects participated in the
experiments simulating moving inside and outside of rooms or cabins with air
conditioning. Skin temperatures and thermal sensation were recorded. Results
showed overshoot and asymmetry of TSV due to the step-change. Skin temperature
changed immediately when subjects entered a new environment. When moving into a
neutral environment from cool, dynamic thermal sensation was in the thermal
comfort zone and overshoot was not obvious. Air-conditioning in a transitional
area should be considered to limit temperature difference to not more than 5
degrees C to decrease the unacceptability of temperature step-change. The linear
relationship between thermal sensation and skin temperature or gradient of skin
temperature does not apply in a step-change environment. There is a significant
linear correlation between TSV and Qloss in the transient environment. Heat loss
from the human skin surface can be used to predict dynamic thermal sensation
instead of the heat transfer of the whole human body.
PMID- 25136809
TI - Stress hyperglycaemia in hospitalised patients and their 3-year risk of diabetes:
a Scottish retrospective cohort study.
AB - BACKGROUND: Hyperglycaemia during hospital admission is common in patients who
are not known to have diabetes and is associated with adverse outcomes. The risk
of subsequently developing type 2 diabetes, however, is not known. We linked a
national database of hospital admissions with a national register of diabetes to
describe the association between admission glucose and the risk of subsequently
developing type 2 diabetes. METHODS AND FINDINGS: In a retrospective cohort
study, patients aged 30 years or older with an emergency admission to hospital
between 2004 and 2008 were included. Prevalent and incident diabetes were
identified through the Scottish Care Information (SCI)-Diabetes Collaboration
national registry. Patients diagnosed prior to or up to 30 days after
hospitalisation were defined as prevalent diabetes and were excluded. The
predicted risk of developing incident type 2 diabetes during the 3 years
following hospital discharge by admission glucose, age, and sex was obtained from
logistic regression models. We performed separate analyses for patients aged 40
and older, and patients aged 30 to 39 years. Glucose was measured in 86,634
(71.0%) patients aged 40 and older on admission to hospital. The 3-year risk of
developing type 2 diabetes was 2.3% (1,952/86,512) overall, was <1% for a glucose
<= 5 mmol/l, and increased to approximately 15% at 15 mmol/l. The risks at 7
mmol/l and 11.1 mmol/l were 2.6% (95% CI 2.5-2.7) and 9.9% (95% CI 9.2-10.6),
respectively, with one in four (21,828/86,512) and one in 40 (1,798/86,512)
patients having glucose levels above each of these cut-points. For patients aged
30-39, the risks at 7 mmol/l and 11.1 mmol/l were 1.0% (95% CI 0.8-1.3) and 7.8%
(95% CI 5.7-10.7), respectively, with one in eight (1,588/11,875) and one in 100
(120/11,875) having glucose levels above each of these cut-points. The risk of
diabetes was also associated with age, sex, and socio-economic deprivation, but
not with specialty (medical versus surgical), raised white cell count, or co
morbidity. Similar results were obtained for pre-specified sub-groups admitted
with myocardial infarction, chronic obstructive pulmonary disease, and stroke.
There were 25,193 deaths (85.8 per 1,000 person-years) over 297,122 person-years,
of which 2,406 (8.1 per 1,000 person-years) were attributed to vascular disease.
Patients with glucose levels of 11.1 to 15 mmol/l and >15 mmol/l had higher
mortality than patients with a glucose of <6.1 mmol/l (hazard ratio 1.54; 95% CI
1.42-1.68 and 2.50; 95% CI 2.14-2.95, respectively) in models adjusting for age
and sex. Limitations of our study include that we did not have data on ethnicity
or body mass index, which may have improved prediction and the results have not
been validated in non-white populations or populations outside of Scotland.
CONCLUSION: Plasma glucose measured during an emergency hospital admission
predicts subsequent risk of developing type 2 diabetes. Mortality was also 1.5
fold higher in patients with elevated glucose levels. Our findings can be used to
inform patients of their long-term risk of type 2 diabetes, and to target
lifestyle advice to those patients at highest risk. Please see later in the
article for the Editors' Summary.
PMID- 25136810
TI - A quantitative prioritisation of human and domestic animal pathogens in Europe.
AB - Disease or pathogen risk prioritisations aid understanding of infectious agent
impact within surveillance or mitigation and biosecurity work, but take
significant development. Previous work has shown the H-(Hirsch-)index as an
alternative proxy. We present a weighted risk analysis describing infectious
pathogen impact for human health (human pathogens) and well-being (domestic
animal pathogens) using an objective, evidence-based, repeatable approach; the H
index. This study established the highest H-index European pathogens.
Commonalities amongst pathogens not included in previous surveillance or risk
analyses were examined. Differences between host types (humans/animals/zoonotic)
in pathogen H-indices were explored as a One Health impact indicator. Finally,
the acceptability of the H-index proxy for animal pathogen impact was examined by
comparison with other measures. 57 pathogens appeared solely in the top 100
highest H-indices (1) human or (2) animal pathogens list, and 43 occurred in
both. Of human pathogens, 66 were zoonotic and 67 were emerging, compared to 67
and 57 for animals. There were statistically significant differences between H
indices for host types (humans, animal, zoonotic), and there was limited evidence
that H-indices are a reasonable proxy for animal pathogen impact. This work
addresses measures outlined by the European Commission to strengthen climate
change resilience and biosecurity for infectious diseases. The results include a
quantitative evaluation of infectious pathogen impact, and suggest greater
impacts of human-only compared to zoonotic pathogens or scientific under
representation of zoonoses. The outputs separate high and low impact pathogens,
and should be combined with other risk assessment methods relying on expert
opinion or qualitative data for priority setting, or could be used to prioritise
diseases for which formal risk assessments are not possible because of data gaps.
PMID- 25136811
TI - Combination effect of epigenetic regulation and ionizing radiation in colorectal
cancer cells.
AB - Exposure of cells to ionizing radiation (IR) induces, not only, activation of
multiple signaling pathways that play critical roles in cell fate determination,
but also alteration of molecular pathways involved in cell death or survival.
Recently, DNA methylation has been established as a critical epigenetic process
involved in the regulation of gene expression in cancer cells, suggesting that
DNA methylation inhibition may be an effective cancer treatment strategy. Because
alterations of gene expression by DNA methylation have been considered to
influence radioresponsiveness, we investigated the effect of a DNA
methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), on
radiosensitivity. In addition, we investigated the underlying cellular mechanisms
of combination treatments of ionizing irradiation (IR) and 5-aza-dC in human
colon cancer cells. Colon cancer cell lines were initially tested for radiation
sensitivity by IR in vitro and were treated with two different doses of 5-aza-dC.
Survival of these cell lines was measured using MTT (3-(4,5-dimethylthiazol-2-yl)
2,5-diphenyltetrazolium bromide) and clonogenic assays. The effects of 5-aza-dC
along with irradiation on cell growth, cell cycle distribution, apoptosis, and
apoptosis-related gene expression were examined. Combination irradiation
treatment with 5-aza-dC significantly decreased growth activity compared with
irradiation treatment alone or with 5-aza-dC treatment alone. The percentage of
HCT116 cells in the sub-G1 phase and their apoptotic rate was increased when
cells were treated with irradiation in combination with 5-aza-dC compared with
either treatment alone. These observations were strongly supported by increased
caspase activity, increased comet tails using comet assays, and increased protein
levels of apoptosis-associated molecules (caspase 3/9, cleaved PARP). Our data
demonstrated that 5-aza-dC enhanced radiosensitivity in colon cancer cells, and
the combination effects of 5-aza-dC with radiation showed greater cellular
effects than that of single treatment, suggesting that the combination of 5-aza
dC and radiation has the potential to become a clinical strategy for the
treatment of cancer.
PMID- 25136812
TI - The Snail transcription factor regulates the numbers of neural precursor cells
and newborn neurons throughout mammalian life.
AB - The Snail transcription factor regulates diverse aspects of stem cell biology in
organisms ranging from Drosophila to mammals. Here we have asked whether it
regulates the biology of neural precursor cells (NPCs) in the forebrain of
postnatal and adult mice, taking advantage of a mouse containing a floxed Snail
allele (Snailfl/fl mice). We show that when Snail is inducibly ablated in the
embryonic cortex, this has long-term consequences for cortical organization. In
particular, when Snailfl/fl mice are crossed to Nestin-cre mice that express Cre
recombinase in embryonic neural precursors, this causes inducible ablation of
Snail expression throughout the postnatal cortex. This loss of Snail causes a
decrease in proliferation of neonatal cortical neural precursors and
mislocalization and misspecification of cortical neurons. Moreover, these
precursor phenotypes persist into adulthood. Adult neural precursor cell
proliferation is decreased in the forebrain subventricular zone and in the
hippocampal dentate gyrus, and this is coincident with a decrease in the number
of adult-born olfactory and hippocampal neurons. Thus, Snail is a key regulator
of the numbers of neural precursors and newborn neurons throughout life.
PMID- 25136813
TI - Gene-specific function prediction for non-synonymous mutations in monogenic
diabetes genes.
AB - The rapid progress of genomic technologies has been providing new opportunities
to address the need of maturity-onset diabetes of the young (MODY) molecular
diagnosis. However, whether a new mutation causes MODY can be questionable. A
number of in silico methods have been developed to predict functional effects of
rare human mutations. The purpose of this study is to compare the performance of
different bioinformatics methods in the functional prediction of nonsynonymous
mutations in each MODY gene, and provides reference matrices to assist the
molecular diagnosis of MODY. Our study showed that the prediction scores by
different methods of the diabetes mutations were highly correlated, but were more
complimentary than replacement to each other. The available in silico methods for
the prediction of diabetes mutations had varied performances across different
genes. Applying gene-specific thresholds defined by this study may be able to
increase the performance of in silico prediction of disease-causing mutations.
PMID- 25136816
TI - Plasma anti-mullerian hormone: an endocrine marker for in vitro embryo production
from Bos taurus and Bos indicus donors.
AB - The aim of this study was to evaluate the association between plasma anti
mullerian hormone (AMH) concentration and in vitro embryo production (IVP) from
Bos taurus (Holstein) and Bos indicus (Nelore) donors. A total of 59 Holstein (15
prepubertal heifers aged 8-10 mo, 15 cyclic heifers aged 12-14 mo, 14 lactating
cows, and 15 nonlactating cows) and 34 Nelore (12 prepubertal heifers aged 10-11
mo, 10 prepubertal heifers aged 21-23 mo, and 12 cyclic heifers aged 24-26 mo)
females were enrolled. All females underwent an ovum pick-up (OPU), without
previous synchronization of the follicular wave, and IVP procedure. Immediately
before the OPU procedure, blood samples were collected for subsequent AMH
determination. A positive correlation was observed between the plasma AMH and
number of in vitro embryos produced from Holstein (r = 0.36, P < 0.001) and
Nelore (r = 0.50, P = 0.003) donors. For additional analyses, donors within each
genotype were classified into 1 of 2 AMH categories (low or high) according to
the average AMH concentration for each genotype. The results revealed that
females classified as having high AMH presented a greater number of visible
aspirated follicles (Holstein: 20.9 +/- 1.5 vs 13.6 +/- 0.9, P < 0.0001; Nelore:
54.3 +/- 6.1 vs 18.6 +/- 2.1, P < 0.0001) and a greater number of recovered
cumulus-oocyte complexes (Holstein: 17.3 +/- 1.5 vs 9.0 +/- 0.9, P < 0.0001;
Nelore: 45.3 +/- 6.4 vs 13.4 +/- 1.7, P < 0.0001). However, there was no
difference in the blastocyst production rate (Holstein: 20.6% +/- 4.0% vs 19.8%
+/- 4.2%, P = 0.60; Nelore: 33.7% +/- 6.5% vs 27.4% +/- 5.5%, P = 0.41, high and
low AMH, respectively). Moreover, donors classified as having high AMH yielded a
greater number of embryos produced per OPU (Holstein: 3.0 +/- 0.7; Nelore: 7.0 +/
1.7) compared with those classified as having low AMH (Holstein: 1.2 +/- 0.3, P
= 0.04; Nelore: 2.2 +/- 0.5, P = 0.007). In conclusion, although the plasma AMH
concentration did not alter the ability of the cumulus-oocyte complex to reach
the blastocyst stage, the AMH concentration in plasma can be an accurate
endocrine marker for the in vitro embryo yield from either B. taurus (Holstein)
or B. indicus (Nelore) donors. Therefore, AMH is a promising tool to enhance the
overall efficiency of OPU-IVP programs in the field as a selective criterion for
high embryo producing donors.
PMID- 25136814
TI - Immobilization of captive tigers (Panthera tigris) with a combination of
tiletamine, zolazepam, and detomidine.
AB - The aims of this study were to evaluate the effects of the administration of a
combination of tiletamine-zolazepam and detomidine (TZD) in 9 tigers (Panthera
tigris). Nine captive tigers were immobilized with tiletamine-zolazepam and
detomidine administered intramuscularly. At the end of the procedure
immobilization was partially reversed with atipamezole. Lateral recumbency was
achieved in 15.6 +/- 5.9 min. The median induction score [scored 1 (excellent) to
4 (poor)] was 1. The immobilization score [scored 1 (poor) to 6 (too deep)] was 5
(4-5) at all study times. After atipamezole administration, all tigers
experienced severe ataxia and incoordination. Median recovery score [scored 1
(excellent) to 4 (poor)] was 2.5 (range 2-3). No neurologic and/or important
adverse reactions were noticed within 5 days after recovery. The combination
tiletamine-zolazepam with detomidine proved to be effective in immobilizing
captive healthy tigers but it maybe associated with hypertension and ataxia
during recovery. Zoo Biol. 34:40-45, 2015. (c) 2014 Wiley Periodicals Inc.
PMID- 25136817
TI - Effervescence-assisted dispersive liquid-liquid microextraction using a solid
effervescent agent as a novel dispersion technique for the analysis of fungicides
in apple juice.
AB - A novel effervescence-assisted dispersive liquid-liquid microextraction method
has been developed for the determination of four fungicides in apple juice
samples. In this method, a solid effervescent agent is added into samples to
assist the dispersion of extraction solvent. The effervescent agent is
environmentally friendly and only produces an increase in the ionic strength and
a negligible variation in the pH value of the aqueous sample, which does not
interfere with the extraction of the analytes. The parameters affecting the
extraction efficiency were investigated including the composition of effervescent
agent, effervescent agent amount, formulation of effervescent agent, adding mode
of effervescent agent, type and volume of extraction solvent, and pH. Under
optimized conditions, the method showed a good linearity within the range of 0.05
2 mg/L for pyrimethanil, fludioxonil, and cyprodinil, and 0.1-4 mg/L for kresoxim
methyl, with the correlation coefficients >0.998. The limits of detection for the
method ranged between 0.005 and 0.01 mg/L. The recoveries of the target
fungicides in apple juice samples were in the range of 72.4-110.8% with the
relative standard deviations ranging from 1.2 to 6.8%.
PMID- 25136818
TI - Synthesis of aromatic (13)C/(2)H-alpha-ketoacid precursors to be used in
selective phenylalanine and tyrosine protein labelling.
AB - Recent progress in protein NMR spectroscopy revealed aromatic residues to be
valuable information sources for performing structure and motion analysis of high
molecular weight proteins. However, the applied NMR experiments require tailored
isotope labelling patterns in order to regulate spin-relaxation pathways and
optimize magnetization transfer. We introduced a methodology to use alpha
ketoacids as metabolic amino acid precursors in cell-based overexpression of
phenylalanine and/or tyrosine labelled proteins in a recent publication, which we
have now developed further by providing synthetic routes to access the
corresponding side-chain labelled precursors. The target compounds allow for
selective introduction of (13)C-(1)H spin systems in a highly deuterated chemical
environment and feature alternating (12)C-(13)C-(12)C ring-patterns. The
resulting isotope distribution is especially suited to render straightforward
(13)C spin relaxation experiments possible, which provide insight into the
dynamic properties of the corresponding labelled proteins.
PMID- 25136819
TI - Demonstration of ultrarapid interfacial formation of 1D fullerene nanorods with
photovoltaic properties.
AB - We demonstrate ultrarapid interfacial formation of one-dimensional (1D) single
crystalline fullerene C60 nanorods at room temperature in 5 s. The nanorods of ~
11 MUm in length and ~ 215 nm in diameter are developed in a hexagonal close-pack
crystal structure, contrary to the cubic crystal structure of pristine C60.
Vibrational and electronic spectroscopy provide strong evidence that the nanorods
are a van der Waals solid, as evidenced from the preservation of the electronic
structure of the C60 molecules within the rods. Steady state optical spectroscopy
reveals a dominance of charge transfer excitonic transitions in the nanorods. A
significant enhancement of photogenerated charge carriers is observed in the
nanorods in comparison to pristine C60, revealing the effect of shape on the
photovoltaic properties. Due to their ultrarapid, large-scale, room-temperature
synthesis with single-crystalline structure and excellent optoelectronic
properties, the nanorods are expected to be promising for photosensitive devices
applications.
PMID- 25136820
TI - Links of justice and rejection sensitivity with aggression in childhood and
adolescence.
AB - Individual differences in justice sensitivity and rejection sensitivity have been
linked to differences in aggressive behavior in adults. However, there is little
research studying this association in children and adolescents and considering
the two constructs in combination. We assessed justice sensitivity from the
victim, observer, and perpetrator perspective as well as anxious and angry
rejection sensitivity and linked both constructs to different forms (physical,
relational), and functions (proactive, reactive) of self-reported aggression and
to teacher- and parent-rated aggression in N = 1,489 9- to 19-year olds in
Germany. Victim sensitivity and both angry and anxious rejection sensitivity
showed positive correlations with all forms and functions of aggression. Angry
rejection sensitivity also correlated positively with teacher-rated aggression.
Perpetrator sensitivity was negatively correlated with all aggression measures,
and observer sensitivity also correlated negatively with all aggression measures
except for a positive correlation with reactive aggression. Path models
considering the sensitivity facets in combination and controlling for age and
gender showed that higher victim justice sensitivity predicted higher aggression
on all measures. Higher perpetrator sensitivity predicted lower physical,
relational, proactive, and reactive aggression. Higher observer sensitivity
predicted lower teacher-rated aggression. Angry rejection sensitivity predicted
higher proactive and reactive aggression, whereas anxious rejection sensitivity
did not make an additional contribution to the prediction of aggression. The
findings are discussed in terms of social information processing models of
aggression in childhood and adolescence.
PMID- 25136821
TI - Instability of trinucleotidic repeats during chromatin remodeling in spermatids.
AB - Transient DNA breaks and evidence of DNA damage response have recently been
reported during the chromatin remodeling process in haploid spermatids, creating
a potential window of enhanced genetic instability. We used flow cytometry to
achieve separation of differentiating spermatids into four highly purified
populations using transgenic mice harboring 160 CAG repeats within exon 1 of the
human Huntington disease gene (HTT). Trinucleotic repeat expansion was found to
occur immediately following the chromatin remodeling steps, confirming the
genetic instability of the process and pointing to the origin of paternal
anticipation observed in some trinucleotidic repeats diseases.
PMID- 25136823
TI - Uniform versus asymmetric shading mediates crown recession in conifers.
AB - In this study we explore the impact of asymmetrical vs. uniform crown shading on
the mortality and growth of upper and lower branches within tree crowns, for two
conifer species: shade intolerant lodgepole pine (Pinus contorta) and shade
tolerant white spruce (Picea glauca). We also explore xylem hydraulics, foliar
nutrition, and carbohydrate status as drivers for growth and expansion of the
lower and upper branches in various types of shading. This study was conducted
over a two-year period across 10 regenerating forest sites dominated by lodgepole
pine and white spruce, in the lower foothills of Alberta, Canada. Trees were
assigned to one of four shading treatments: (1), complete uniform shading of the
entire tree, (2) light asymmetric shading where the lower 1/4-1/3 of the tree
crown was shaded, (3) heavy asymmetric shading as in (2) except with greater
light reduction and (4) control in which no artificial shading occurred and most
of the entire crown was exposed to full light. Asymmetrical shading of only the
lower crown had a larger negative impact on the bud expansion and growth than did
uniform shading, and the effect was stronger in pine relative to spruce. In
addition, lower branches in pine also had lower carbon reserves, and reduced
xylem-area specific conductivity compared to spruce. For both species, but
particularly the pine, the needles of lower branches tended to store less C than
upper branches in the asymmetric shade, which could suggest a movement of
reserves away from the lower branches. The implications of these findings
correspond with the inherent shade tolerance and self-pruning behavior of these
conifers and supports a carbon based mechanism for branch mortality--mediated by
an asymmetry in light exposure of the crown.
PMID- 25136824
TI - Differential axonal conduction patterns of mechano-sensitive and mechano
insensitive nociceptors--a combined experimental and modelling study.
AB - Cutaneous pain sensations are mediated largely by C-nociceptors consisting of
both mechano-sensitive (CM) and mechano-insensitive (CMi) fibres that can be
distinguished from one another according to their characteristic axonal
properties. In healthy skin and relative to CMi fibres, CM fibres show a higher
initial conduction velocity, less activity-dependent conduction velocity slowing,
and less prominent post-spike supernormality. However, after sensitization with
nerve growth factor, the electrical signature of CMi fibres changes towards a
profile similar to that of CM fibres. Here we take a combined experimental and
modelling approach to examine the molecular basis of such alterations to the
excitation thresholds. Changes in electrical activation thresholds and activity
dependent slowing were examined in vivo using single-fibre recordings of CM and
CMi fibres in domestic pigs following NGF application. Using computational
modelling, we investigated which axonal mechanisms contribute most to the
electrophysiological differences between the fibre classes. Simulations of axonal
conduction suggest that the differences between CMi and CM fibres are strongly
influenced by the densities of the delayed rectifier potassium channel (Kdr), the
voltage-gated sodium channels NaV1.7 and NaV1.8, and the Na+/K+-ATPase.
Specifically, the CM fibre profile required less Kdr and NaV1.8 in combination
with more NaV1.7 and Na+/K+-ATPase. The difference between CM and CMi fibres is
thus likely to reflect a relative rather than an absolute difference in protein
expression. In support of this, it was possible to replicate the experimental
reduction of the ADS pattern of CMi nociceptors towards a CM-like pattern
following intradermal injection of nerve growth factor by decreasing the
contribution of Kdr (by 50%), increasing the Na+/K+-ATPase (by 10%), and reducing
the branch length from 2 cm to 1 cm. The findings highlight key molecules that
potentially contribute to the NGF-induced switch in nociceptors phenotype, in
particular NaV1.7 which has already been identified clinically as a principal
contributor to chronic pain states such as inherited erythromelalgia.
PMID- 25136825
TI - Deep brain stimulation of the antero-medial globus pallidus interna for Tourette
syndrome.
AB - BACKGROUND: We have previously reported the results of Deep Brain Stimulation
(DBS) of the antero-medial globus pallidus interna (GPi) for severe Tourette
Syndrome (TS) in 11 patients. We extend this case series to 17 patients and a
longer follow-up to a maximum of 46 months. METHODS: 17 patients (14 male; mean
age 29.1 years, range 17-51 years) with severe and medically intractable TS were
implanted with Medtronic quadripolar electrodes bilaterally in the antero-medial
GPi. The primary outcome measure was the Yale Global Tic Severity Scale (YGTSS).
Secondary outcome measures included the Yale-Brown Obsessive Compulsive Scale,
Hamilton Depression Rating Scale, Gilles de la Tourette Quality of Life Scale and
Global Assessment of Functioning. Follow up was at one month, three months and
finally at a mean 24.1 months (range 8-46 months) following surgery. RESULTS:
Overall, there was a 48.3% reduction in motor tics and a 41.3% reduction in
phonic tics at one month, and this improvement was maintained at final follow-up.
12 out of 17 (70.6%) patients had a>50% reduction in YGTSS score at final follow
up. Only 8 patients required ongoing pharmacotherapy for tics post-surgery.
Patients improved significantly on all secondary measures. Adverse consequences
included lead breakage in 4 patients, infection (1), transient anxiety (2),
dizziness (1), poor balance (1) and worsening of stuttering (1). CONCLUSIONS:
This case series provides further support that antero-medial GPi DBS is an
effective and well tolerated treatment for a subgroup of severe TS, with benefits
sustained up to 4 years.
PMID- 25136828
TI - Environmental factors associated with success rates of Australian stock herding
dogs.
AB - This study investigated the current management practices associated with stock
herding dogs on Australian farms. A parallel goal was to determine whether these
practices and the characteristics of the dog handlers were associated with
success rates. Success rate refers to the proportion of dogs acquired by the
farmer that were retained as working dogs. Data on a total of 4,027 dogs were
obtained through The Farm Dog Survey which gathered information from 812 herding
dog owners around Australia. Using logistic regression, significant associations
were identified between success rate and seven variables: dog breed, housing
method, trial participation, age of the dog at acquisition, electric collar use,
hypothetical maximum treatment expenditure and the conscientiousness score of the
owner's personality. These findings serve as a guide to direct further research
into ways of optimising herding dog performance and welfare. They emphasise the
importance of not only examining the genetic predispositions of the working dog
but also the impact the handler can have on a dog's success in the workplace.
PMID- 25136826
TI - The flavones apigenin and luteolin induce FOXO1 translocation but inhibit
gluconeogenic and lipogenic gene expression in human cells.
AB - The flavones apigenin (4',5,7,-trihydroxyflavone) and luteolin (3',4',5,7,
tetrahydroxyflavone) are plant secondary metabolites with antioxidant,
antiinflammatory, and anticancer activities. We evaluated their impact on cell
signaling pathways related to insulin-resistance and type 2 diabetes. Apigenin
and luteolin were identified in our U-2 OS (human osteosarcoma) cell screening
assay for micronutrients triggering rapid intracellular translocation of the
forkhead box transcription factor O1 (FOXO1), an important mediator of insulin
signal transduction. Insulin reversed the translocation of FOXO1 as shown by live
cell imaging. The impact on the expression of target genes was evaluated in HepG2
(human hepatoma) cells. The mRNA-expression of the gluconeogenic enzymes
phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pc), the
lipogenic enzymes fatty-acid synthase (FASN) and acetyl-CoA-carboxylase (ACC)
were down-regulated by both flavones with smaller effective dosages of apigenin
than for luteolin. PKB/AKT-, PRAS40-, p70S6K-, and S6-phosphorylation was reduced
by apigenin and luteolin but not that of the insulin-like growth factor receptor
IGF-1R by apigenin indicating a direct inhibition of the PKB/AKT-signaling
pathway distal to the IGF-1 receptor. N-acetyl-L-cysteine did not prevent FOXO1
nuclear translocation induced by apigenin and luteolin, suggesting that these
flavones do not act via oxidative stress. The roles of FOXO1, FOXO3a, AKT,
sirtuin1 (SIRT1), and nuclear factor (erythroid-derived2)-like2 (NRF2),
investigated by siRNA knockdown, showed differential patterns of signal pathways
involved and a role of NRF2 in the inhibition of gluconeogenic enzyme expression.
We conclude that these flavones show an antidiabetic potential due to reduction
of gluconeogenic and lipogenic capacity despite inhibition of the PKB/AKT pathway
which justifies detailed investigation in vivo.
PMID- 25136829
TI - No correlation between TIMP2 -418 G>C polymorphism and increased risk of cancer:
evidence from a meta-analysis.
AB - AIM: Tissue inhibitor of metalloproteinase (TIMP2) is involved in the regulation
of matrix metalloproteinase 2 (MMP2) and shown to implicate in cancer development
and progression. The results from the published studies based on the association
between TIMP2 -418 G>C polymorphism and cancer risk are inconsistent. In this
meta-analysis, we aimed to evaluate the potential association between TIMP2 -418
G>C polymorphism and cancer risk. METHODOLOGY: We searched PubMed (Medline) and
EMBASE web databases to cover all studies based on relationship of TIMP2 -418 G>C
polymorphism and risk of cancer until October 2013. The meta-analysis was
performed for selected case-control studies and pooled odds ratios (ORs) and 95%
confidence intervals (95% CIs) were calculated for all genetic models. RESULTS: A
total of 2225 cancer cases and 2532 controls were included from ten eligible case
control studies. Results from overall pooled analysis suggested no evidence of
significant risk between TIMP2 -418 G>C polymorphism and cancer risk in any of
the genetic models, such as, allele (C vs. G: OR = 1.293, 95% CI = 0.882 to
1.894, p = 0.188), homozygous (CC vs. GG: OR = 0.940, 95% CI = 0.434 to 2.039, p
= 0.876), heterozygous (GC vs. GG: OR = 1.397, 95% CI = 0.888 to 2.198, p =
0.148), dominant (CC+GC vs. GG: OR = 1.387, 95% CI = 0.880 to 2.187, p = 0.159)
and recessive (CC vs. GG+GC: OR = 0.901, 95% CI = 0.442 to 1.838, p = 0.774)
models. No evidence of publication bias was detected during the analysis.
CONCLUSIONS: The present meta-analysis suggests that the TIMP2 -418 G>C
polymorphism may not be involved in predisposing risk factor for cancer in
overall population. However, future larger studies with group of populations are
needed to analyze the possible correlation.
PMID- 25136830
TI - Characterization of the regulatory mechanisms of activating transcription factor
3 by hypertrophic stimuli in rat cardiomyocytes.
AB - AIMS: Activating transcription factor 3 (ATF3) is a stress-activated immediate
early gene suggested to have both detrimental and cardioprotective role in the
heart. Here we studied the mechanisms of ATF3 activation by hypertrophic stimuli
and ATF3 downstream targets in rat cardiomyocytes. METHODS AND RESULTS: When
neonatal rat cardiomyocytes were exposed to endothelin-1 (ET-1, 100 nM) and
mechanical stretching in vitro, maximal increase in ATF3 expression occurred at 1
hour. Inhibition of extracellular signal-regulated kinase (ERK) by PD98059
decreased ET-1- and stretch-induced increase of ATF3 protein but not ATF3 mRNA
levels, whereas protein kinase A (PKA) inhibitor H89 attenuated both ATF3 mRNA
transcription and protein expression in response to ET-1 and stretch. To
characterize further the regulatory mechanisms upstream of ATF3, p38 mitogen
activated protein kinase (MAPK) signaling was investigated using a gain-of
function approach. Adenoviral overexpression of p38alpha, but not p38beta,
increased ATF3 mRNA and protein levels as well as DNA binding activity. To
investigate the role of ATF3 in hypertrophic process, we overexpressed ATF3 by
adenovirus-mediated gene transfer. In vitro, ATF3 gene delivery attenuated the
mRNA transcription of interleukin-6 (IL-6) and plasminogen activator inhibitor-1
(PAI-1), and enhanced nuclear factor-kappaB (NF-kappaB) and Nkx-2.5 DNA binding
activities. Reduced PAI-1 expression was also detected in vivo in adult rat heart
by direct intramyocardial adenovirus-mediated ATF3 gene delivery. CONCLUSIONS:
These data demonstrate that ATF3 activation by ET-1 and mechanical stretch is
partly mediated through ERK and cAMP-PKA pathways, whereas p38 MAPK pathway is
involved in ATF3 activation exclusively through p38alpha isoform. ATF3 activation
caused induction of modulators of the inflammatory response NF-kappaB and Nkx
2.5, as well as attenuation of pro-fibrotic and pro-inflammatory proteins IL-6
and PAI-1, suggesting cardioprotective role for ATF3 in the heart.
PMID- 25136831
TI - A quantitative comparison of single-cell whole genome amplification methods.
AB - Single-cell sequencing is emerging as an important tool for studies of genomic
heterogeneity. Whole genome amplification (WGA) is a key step in single-cell
sequencing workflows and a multitude of methods have been introduced. Here, we
compare three state-of-the-art methods on both bulk and single-cell samples of E.
coli DNA: Multiple Displacement Amplification (MDA), Multiple Annealing and
Looping Based Amplification Cycles (MALBAC), and the PicoPLEX single-cell WGA kit
(NEB-WGA). We considered the effects of reaction gain on coverage uniformity,
error rates and the level of background contamination. We compared the
suitability of the different WGA methods for the detection of copy-number
variations, for the detection of single-nucleotide polymorphisms and for de-novo
genome assembly. No single method performed best across all criteria and
significant differences in characteristics were observed; the choice of which
amplifier to use will depend strongly on the details of the type of question
being asked in any given experiment.
PMID- 25136832
TI - The transient receptor potential vanilloid 2 cation channel is abundant in
macrophages accumulating at the peri-infarct zone and may enhance their migration
capacity towards injured cardiomyocytes following myocardial infarction.
AB - PURPOSE: A novel family of transient receptor potential (TRP) channels, that may
hold a role in calcium homeostasis, has recently been described. By employing a
GeneChip array analysis we have demonstrated a clear and specific upregulation of
the TRP vanilloid 2 (TRPV2) mRNA in the left ventricles (LV) 3-5 days post-acute
myocardial infarction (MI) compared to sham-operated controls, both in rats and
in mice. We sought to characterize the cardiac cellular subpopulations in which
TRPV2 is overexpressed upon acute MI. METHODS: Lewis rats underwent an acute MI
by ligation of the left anterior descending artery or chest opening only (sham).
The animals were terminated at various time points and an immunohistochemical
(IHC) and immunofluorescent (IFC) staining of the LV sections as well as a flow
cytometry analysis of LV-derived cells were carried out, using anti-TRPV2 and
anti-monocyte/macrophage antibodies. Rat alveolar macrophage cells, NR8383,
transiently transfected with TRPV2 siRNA were allowed to migrate towards hypoxic
conditioned media of the rat cardiac myoblast line H9C2 using a trans-well
migration assay. The macrophage cells migrating to the bottom side of the inserts
were counted. RESULTS: The IHC and IFC staining as well as the flow cytometry
data demonstrated a substantial expression of TRPV2 in infiltrating macrophages
in the peri-infarct region 3-5 days post-acute MI. The in vitro migration assay
data demonstrated that following inhibition of the TRPV2 channel, the number of
migrating macrophages towards conditioned medium of hypoxic cardiomyocytes was
significantly reduced. CONCLUSIONS: TRPV2 is highly expressed on the peri-infarct
infiltrating macrophages and may play an important role in post-MI phagocytosis.
Better characterization of this channel may pave the way for identifying a new
target for modulating the dramatic post-MI immune reactions.
PMID- 25136833
TI - HLXB9 gene expression, and nuclear location during in vitro neuronal
differentiation in the SK-N-BE neuroblastoma cell line.
AB - Different parts of the genome occupy specific compartments of the cell nucleus
based on the gene content and the transcriptional activity. An example of this is
the altered nuclear positioning of the HLXB9 gene in leukaemia cells observed in
association with its over-expression. This phenomenon was attributed to the
presence of a chromosomal translocation with breakpoint proximal to the HLXB9
gene. Before becoming an interesting gene in cancer biology, HLXB9 was studied as
a developmental gene. This homeobox gene is also known as MNX1 (motor neuron and
pancreas homeobox 1) and it is relevant for both motor neuronal and pancreatic
beta cells development. A spectrum of mutations in this gene are causative of
sacral agenesis and more broadly, of what is known as the Currarino Syndrome, a
constitutional autosomal dominant disorder. Experimental work on animal models
has shown that HLXB9 has an essential role in motor neuronal differentiation.
Here we present data to show that, upon treatment with retinoic acid, the HLXB9
gene becomes over-expressed during the early stages of neuronal differentiation
and that this corresponds to a reposition of the gene in the nucleus. More
precisely, we used the SK-N-BE human neuroblastoma cell line as an in vitro model
and we demonstrated a transient transcription of HLXB9 at the 4th and 5th days of
differentiation that corresponded to the presence, predominantly in the cell
nuclei, of the encoded protein HB9. The nuclear positioning of the HLXB9 gene was
monitored at different stages: a peripheral location was noted in the
proliferating cells whereas a more internal position was noted during
differentiation, that is while HLXB9 was transcriptionally active. Our findings
suggest that HLXB9 can be considered a marker of early neuronal differentiation,
possibly involving chromatin remodeling pathways.
PMID- 25136834
TI - Complement factor H, vitronectin, and opticin are tyrosine-sulfated proteins of
the retinal pigment epithelium.
AB - Lack of tyrosine sulfation of ocular proteins results in disorganized
photoreceptor structure and drastically reduced visual function, demonstrating
the importance of this post-translational modification to vision. To understand
the role that tyrosine sulfation plays in the function of ocular proteins, we
identified some tyrosine-sulfated proteins in the retinal pigment epithelium
using two independent methods, immuno-affinity column purification with an anti
sulfotyrosine specific antibody and computer-based sequence analysis of retinal
pigment epithelium secretome by means of the prediction program Sulfinator.
Radioactive labeling followed by thin layer electrophoresis revealed that three
proteins, vitronectin, opticin, and complement factor H (CFH), were post
translationally modified by tyrosine sulfation. The identification of vitronectin
and CFH as tyrosine-sulfated proteins is significant, since both are deposited in
drusen in the eyes of patients with age-related macular degeneration (AMD).
Furthermore, mutations in CFH have been determined to be a major risk factor in
the development of AMD. Future studies that seek to understand the role of CFH in
the development of AMD should take into account the role that tyrosine sulfation
plays in the interaction of this protein with its partners, and examine whether
modulating sulfation provides a potential therapeutic target.
PMID- 25136835
TI - NLRP3 gene silencing ameliorates diabetic cardiomyopathy in a type 2 diabetes rat
model.
AB - BACKGROUND: Nucleotide-binding oligomerization domain-like receptor protein 3
(NLRP3) inflammasome is associated with metabolic disorder and cell death, which
are important triggers in diabetic cardiomyopathy (DCM). We aimed to explore
whether NLRP3 inflammasome activation contributes to DCM and the mechanism
involved. METHODS: Type 2 diabetic rat model was induced by high fat diet and low
dose streptozotocin. The characteristics of type 2 DCM were evaluated by
metabolic tests, echocardiography and histopathology. Gene silencing therapy was
used to investigate the role of NLRP3 in the pathogenesis of DCM. High glucose
treated H9c2 cardiomyocytes were used to determine the mechanism by which NLRP3
modulated the DCM. The cell death in vitro was detected by TUNEL and EthD-III
staining. TXNIP-siRNA and pharmacological inhibitors of ROS and NF-kB were used
to explore the mechanism of NLRP3 inflammasome activation. RESULTS: Diabetic rats
showed severe metabolic disorder, cardiac inflammation, cell death, disorganized
ultrastructure, fibrosis and excessive activation of NLRP3, apoptosis-associated
speck-like protein containing a caspase recruitment domain (ASC), pro-caspase-1,
activated caspase-1 and mature interleukin-1beta (IL-1beta). Evidence for
pyroptosis was found in vivo, and the caspase-1 dependent pyroptosis was found in
vitro. Silencing of NLRP3 in vivo did not attenuate systemic metabolic
disturbances. However, NLRP3 gene silencing therapy ameliorated cardiac
inflammation, pyroptosis, fibrosis and cardiac function. Silencing of NLRP3 in
H9c2 cardiomyocytes suppressed pyroptosis under high glucose. ROS inhibition
markedly decreased nuclear factor-kB (NF-kB) phosphorylation, thioredoxin
interacting/inhibiting protein (TXNIP), NLRP3 inflammasome, and mature IL-1beta
in high glucose treated H9c2 cells. Inhibition of NF-kB reduced the activation of
NLRP3 inflammasome. TXNIP-siRNA decreased the activation of caspase-1 and IL
1beta. CONCLUSION: NLRP3 inflammasome contributed to the development of DCM. NF
kappaB and TXNIP mediated the ROS-induced caspase-1 and IL-1beta activation,
which are the effectors of NLRP3 inflammasome. NLRP3 gene silencing may exert a
protective effect on DCM.
PMID- 25136836
TI - Light scattering sensor for direct identification of colonies of Escherichia coli
serogroups O26, O45, O103, O111, O121, O145 and O157.
AB - BACKGROUND: Shiga-toxin producing Escherichia coli (STEC) have emerged as
important foodborne pathogens, among which seven serogroups (O26, O45, O103,
O111, O121, O145, O157) are most frequently implicated in human infection. The
aim was to determine if a light scattering sensor can be used to rapidly identify
the colonies of STEC serogroups on selective agar plates. METHODOLOGY/PRINCIPAL
FINDINGS: Initially, a total of 37 STEC strains representing seven serovars were
grown on four different selective agar media, including sorbitol MacConkey
(SMAC), Rainbow Agar O157, BBL CHROMagarO157, and R&F E. coli O157:H7, as well as
nonselective Brain Heart Infusion agar. The colonies were scanned by an automated
light scattering sensor, known as BARDOT (BActerial Rapid Detection using Optical
scattering Technology), to acquire scatter patterns of STEC serogroups, and the
scatter patterns were analyzed using an image classifier. Among all of the
selective media tested, both SMAC and Rainbow provided the best differentiation
results allowing multi-class classification of all serovars with an average
accuracy of more than 90% after 10-12 h of growth, even though the colony
appearance was indistinguishable at that early stage of growth. SMAC was chosen
for exhaustive scatter image library development, and 36 additional strains of
O157:H7 and 11 non-O157 serovars were examined, with each serogroup producing
unique differential scatter patterns. Colony scatter images were also tested with
samples derived from pure and mixed cultures, as well as experimentally
inoculated food samples. BARDOT accurately detected O157 and O26 serovars from a
mixed culture and also from inoculated lettuce and ground beef (10-h broth
enrichment +12-h on-plate incubation) in the presence of natural background
microbiota in less than 24 h. CONCLUSIONS: BARDOT could potentially be used as a
screening tool during isolation of the most important STEC serovars on selective
agar plates from food samples in less than 24 h.
PMID- 25136838
TI - Solvent-assisted electrospray ionization for direct analysis of various compounds
(complex) from low/nonpolar solvents and eluents.
AB - Electrospray ionization (ESI) is a powerful ionization technique with a wide
range of applications. However, the analytes in low/nonpolar solvents cannot be
analyzed directly in electrospray ionization-mass spectrometry (ESI-MS), because
low/nonpolar solvents are incompatible with ESI, because of their low
conductivity. To circumvent this problem, we introduce an electrospray-based
ionization method termed solvent-assisted electrospray ionization (SAESI). With
the help of electrospray solvents at the tip of the spray needle, compounds in
"non-electrospray ionization-friendly" solvents can be ionized directly using
solvent-assisted electrospray ionization-mass spectrometry (SAESI-MS). The key
features that the assistant solvent can be chosen flexibly and makes little
interference to samples lead to better ionization performance in detection of
organic reaction intermediates and real-time analysis of polymers and chiral
drugs separated by gel permeation chromatography (GPC) and normal phase liquid
chromatography (NPLC). Furthermore, it can achieve online hydrogen/deuterium
(H/D) exchange reaction and even mitigate the signal suppression caused by strong
acid modifiers in liquid chromatography. In addition, all parts of this device
are commercially available and it only requires two parameters to be optimized,
which makes SAESI easy to handle.
PMID- 25136837
TI - Metabolic characterization of adults with binge eating in the general population:
the Framingham Heart Study.
AB - OBJECTIVE: To describe the metabolic profile of individuals with objective binge
eating (OBE) and to evaluate whether associations between OBE and metabolic risk
factors are mediated by body mass index (BMI). METHODS: Participants from the
Framingham Heart Study, Third Generation and Omni 2 cohorts (n = 3,551, 53.1%
women, mean age 46.4 years) were screened for binge eating. Multivariable
adjusted regression models to examine the associations of OBE with metabolic risk
factors were used. RESULTS: The prevalence of OBE was 4.8% in women and 4.9% in
men. Compared to non-binge eating, OBE was associated with higher odds of
hypertension (OR 1.85, 95% CI 1.32-2.60), hypertriglyceridemia (OR 1.42, 95% CI
1.01-2.01), low HDL (OR 1.70, 95% CI 1.18-2.44), insulin resistance (OR 3.18, 95%
CI 2.25-4.50) and metabolic syndrome (OR 2.75, 95% CI 1.94-3.90). Fasting glucose
was 7.2 mg dl(-1) higher in those with OBE (P = 0.0001). Individuals with OBE had
more visceral, subcutaneous and liver fat. Most of these associations were
attenuated with adjustment for BMI, with the exception of fasting glucose.
CONCLUSIONS: Binge eating is associated with a high burden of metabolic risk
factors. Much of the associated risk appears to be mediated by BMI, with the
exception of fasting glucose.
PMID- 25136839
TI - Extracellular vesicles as a platform for 'liquid biopsy' in glioblastoma
patients.
AB - Extracellular vesicles (EVs) are cell-secreted vesicles that range from 30-2000
nm in size. These vesicles are secreted by both normal and neoplastic cells.
Physiologically, EVs serve multiple critical biologic functions, including
cellular remodeling, intracellular communication, modulation of the tumor
microenvironment and regulation of immune function. Because EVs contain genetic
and proteomic contents that reflect the cell of origin, it is possible to detect
tumor-specific material in EVs secreted by cancer cells. Importantly, EVs
secreted by cancer cells transgress anatomic compartments and can be detected in
the blood, cerebrospinal fluid, and other biofluids of cancer patients. In this
context, there is a growing interest in analyzing EVs from the biofluid of cancer
patients as a means of disease diagnosis and therapeutic monitoring. In this
article, we review the development of EVs as a diagnostic platform for the most
common form of brain cancer, glioblastoma, discuss potential clinical
translational opportunities and identify the central challenges associated with
future clinical applications.
PMID- 25136841
TI - The diagnosis accuracy of PLA2R-AB in the diagnosis of idiopathic membranous
nephropathy: a meta-analysis.
AB - BACKGROUND: The presence of antibodies against the M-type phospholipase A2
receptor (PLA2R-AB) is considered to be a promising serological diagnostic
biomarker of idiopathic membranous nephropathy (iMN). However, controversy
remains about the diagnostic accuracy of serum PLA2R-AB testing. Here, we
performed a comprehensive meta-analysis to assess the overall diagnostic value of
serum PLA2R-AB testing in iMN detection. METHODS: PubMed, Embase, and CNKI
(Chinese National Knowledge Infrastructure) were searched for relevant original
articles through January 31, 2014. The summary sensitivity, specificity, positive
likelihood ratio, negative likelihood ratio and diagnostic odds ratio (DOR) were
estimated using the bivariate model. The heterogeneity among studies was explored
by subgroup and meta-regression analysis. RESULTS: 9 articles, including 15
studies, were eventually identified with a total of 2212 patients. The summary
sensitivity of all studies is 78% (95% CI: 66% to 87%) and the specificity is 99%
(95% CI: 96% to 100%). The summary positive and negative likelihood ratios are
96.1 (95% CI, 19.5 to 472.1) and 0.22 (95% CI: 0.14 to 0.35), respectively. The
DOR is 437 (95%CI, 74 to 2592). The subgroup analysis and meta-regression suggest
the test interval is the main source of heterogeneity. CONCLUSIONS: Serum PLA2R
AB testing is a useful tool to detect iMN. In addition, considering the high
heterogeneity and potential publication bias, further high quality studies are
needed in the future.
PMID- 25136840
TI - The promise of methylation on beads for cancer detection and treatment.
AB - Despite numerous technical hurdles, the realization of true personalized medicine
is becoming a progressive reality for the future of patient care. With the
development of new techniques and tools to measure the genetic signature of
tumors, biomarkers are increasingly being used to detect occult tumors, determine
the choice of treatment and predict outcomes. Methylation of CpG islands at the
promoter region of genes is a particularly exciting biomarker as it is cancer
specific. Older methods to detect methylation were cumbersome, operator-dependent
and required large amounts of DNA. However, a newer technique called methylation
on beads has resulted in a more uniform, streamlined and efficient assay.
Furthermore, methylation on beads permits the extraction and processing of
miniscule amounts of methylated tumor DNA in the peripheral blood. Such a
technique may aid in the clinical detection and treatment of cancers in the
future.
PMID- 25136842
TI - Advanced disease at enrollment in HIV care in four sub-Saharan African countries:
change from 2006 to 2011 and multilevel predictors in 2011.
AB - OBJECTIVES: To examine changes between 2006 and 2011 in the proportion of HIV
positive patients newly enrolled in HIV care with advanced disease and the median
CD4 cell count at enrollment; and identify patient, facility, and contextual
level factors associated with late enrollment in care in 2011. DESIGN: Cross
sectional over time. METHODS: For time-trends analyses, routinely collected
patient-level data (307 110 adults newly enrolled in 138 HIV clinical care
facilities) in Kenya, Mozambique, Rwanda and Tanzania; and for analyses of
correlates, patient-level data (46 201 in 195 facilities), and facility and
population-level survey data were used. Late enrollment was defined as CD4 cell
count 350 cells/MUl or less and/or WHO clinical stage 3/4. RESULTS: Late
enrollment declined from 69.9 to 57.2% (P < 0.0001); median CD4 cell count
increased from 242 to 292 cells/MUl (Ptrend < 0.0001). In 2011, risk of late
enrollment was significantly higher for men and nonpregnant women vs. pregnant
women; patients aged above 25 vs. 15-25 years; nonmarried vs. married; and those
entering from sites other than prevention of mother-to-child transmission. More
extensive HIV testing coverage in the region of a facility was significantly
associated with lower risk of late enrollment. CONCLUSIONS: Despite improvement,
in 2011, 57% of patients entered HIV care who were already antiretroviral therapy
eligible. The lower risk of late enrollment among those referred from prevention
of mother-to-child transmission and in regions where HIV testing coverage was
higher suggests that innovative approaches to rapidly increase testing uptake
among people living with HIV prior to the development of symptoms have the
potential to reduce late enrollment in care.
PMID- 25136844
TI - Repeated measurements of NT-pro-B-type natriuretic peptide, troponin T or C
reactive protein do not predict future allograft rejection in heart transplant
recipients.
AB - BACKGROUND: Studies on the prognostic value of serial biomarker assays for future
occurrence of allograft rejection (AR) are scarce. We examined whether repeated
measurements of NT-pro-B-type natriuretic peptide (NT-proBNP), troponin T (TropT)
and C-reactive protein (CRP) predict AR. METHODS: From 2005 to 2010, 77
consecutive heart transplantation (HTx) recipients were included. The NT-proBNP,
TropT, and CRP were measured at 16 +/- 4 (mean +/- standard deviation)
consecutive routine endomyocardial biopsy surveillance visits during the first
year of follow-up. Allograft rejection was defined as International Society for
Heart and Lung Transplantation (ISHLT) grade 2R or higher at endomyocardial
biopsy. Joint modeling was used to assess the association between repeated
biomarker measurements and occurrence of future AR. Joint modeling accounts for
dependence among repeated observations in individual patients. RESULTS: The mean
age of the patients at HTx was 49 +/- 9.2 years, and 68% were men. During the
first year of follow-up, 1,136 biopsies and concurrent blood samples were
obtained, and 56 patients (73%) experienced at least one episode of AR. All
biomarkers were elevated directly after HTx and achieved steady-state after ~ 12
weeks, both in patients with or without AR. No associations were present between
the repeated measurements of NT-proBNP, TropT, or CRP and AR both early (weeks 0
12) and late (weeks 13-52) in the course after HTx (hazard ratios for weeks 13
52: 0.96 (95% confidence interval, 0.55-1.68), 0.67 (0.27-1.69), and 1.44 (0.90
2.30), respectively, per ln[unit]). Combining the three biomarkers in one model
also rendered null results. CONCLUSION: The temporal evolution of NT-proBNP,
TropT, and CRP before AR did not predict occurrence of acute AR both in the early
and late course of the first year after HTx.
PMID- 25136843
TI - Satisfaction With Life Among Living Kidney Donors: A RELIVE Study of Long-Term
Donor Outcomes.
AB - BACKGROUND: Little is known about living kidney donors' satisfaction with life
(SWL) after donation. We compared donors' SWL to previously reported general
population samples and investigated predictors of donors' SWL. METHODS: Three
transplant centers mailed questionnaires to assess SWL, physical health,
optimism, retrospective evaluation of the donation experience, and demographic
characteristics to living kidney donors' homes between 2010 and 2012. Two
thousand four hundred fifty-five donors who were between 5 and 48 years from the
time of their donor surgery completed the questionnaire. RESULTS: Eighty-four
percent of donors were satisfied with their lives (scores >= 20 on the
Satisfaction With Life Scale). Donors were at least as satisfied with their lives
as previously reported general population samples. After adjusting for physical
health, optimism, and demographics, donors' SWL was significantly associated with
donors' recalled experience of donation. Social support and positive effects of
the donation on relationships predicted greater SWL. Financial difficulties
associated with donation and longer recovery times predicted lower SWL. Recipient
outcomes were not significantly related to donor SWL. DISCUSSION: Limitations
include the lack of predonation SWL data, potential bias in postdonation SWL
because of the situational context of the questionnaire, and a sample that is not
representative of all U.S. living kidney donors. Nonetheless, strategies focused
on improving the donation experience, particularly related to recovery time,
financial issues, and social support, may result in greater SWL after donation.
PMID- 25136845
TI - Compensatory hypertrophy of the remaining kidney in medically complex living
kidney donors over the long term.
AB - BACKGROUND: The criteria for living kidney donation are changing, resulting in
increased numbers of individuals with risk factors being accepted as donors. The
long-term function and volume changes in the remaining kidney of these medically
complex donors remain largely unknown. METHODS: Living kidney donors with three
separate risk factors (older age, obesity, or hypertension) were reevaluated 5
years after donation. The function and volume of the remaining kidney were
assessed and compared to those of standard donors. RESULTS: The body size
correlated significantly with the kidney size and glomerular filtration rate
(GFR) at the time of donation. Five years after donation, the remaining kidney
size increased by a mean of 29.3%, and the GFR by 35.6%. The increase in GFR was
uniform. In univariate analysis, neither the changes in the size nor the changes
in the 1GFR were found to be associated with the risk factors. CONCLUSION:
Medically complex living donors demonstrate similar compensatory increase in
function and volume of the remaining kidney compared to standard donors, 5 years
after donation.
PMID- 25136846
TI - "Early" withdrawal of glucocorticosteroids is well tolerated by kidney transplant
recipients without increasing allograft rejection while preserving bone
integrity.
PMID- 25136847
TI - Protective effect of neutralization of the extracellular high-mobility group box
1 on renal ischemia-reperfusion injury in miniature swine.
AB - BACKGROUND: Strategies that reduce ischemia-reperfusion injury (IRI) have the
potential to expand the numbers of available organs for transplantation. Recent
reports in rodent models have demonstrated that high-mobility group box 1 (HMGB1)
acts as an alarm in initiating the inflammatory response resulting from ischemic
injury. The aim of this study was to evaluate the cytoprotective effects of anti
HMGB1 antibodies on renal IRI in preclinical large animals. METHODS: One hundred
twenty minutes of warm and 60 min of cold renal ischemia were induced in 8 CLAWN
miniature swine. Three of eight animals received intravenous anti-HMGB1 antibody
at 1 mg/kg just before the reperfusion of renal blood flow. Renal function was
assessed by serum creatinine and renal biopsy. Serum levels of interleukin (IL)
1beta, IL-6, and HMGB1 were measured. RESULTS: The concentration of HMGB1
increased as early as 30 min after reperfusion and before the elevation of IL
1beta and IL-6. Serum creatinine levels were markedly elevated, peaking at a
median of 5 days (peak creatinine levels: 11.6 +/- 1.6 mg/dL) and recovering by
day 14. Anti-HMGB1 antibody injection dramatically decreased renal damage as well
as serum levels of HMGB1 associated with IRI. Renal function returned to near
normal by day 9, and peak creatinine levels were markedly lower (7.4 +/- 0.2
mg/dL), and biopsies possessed fewer pathologic changes when compared to the
control group. CONCLUSION: In this study, we demonstrated the beneficial effects
of perioperative administration of anti-HMGB1 antibody in reducing renal IRI in a
clinically relevant, large animal model.
PMID- 25136850
TI - Adherence to the 2010 American College of Cardiology Foundation Appropriate Use
Criteria for Cardiac Computed Tomography: Quality Analysis at a Tertiary Referral
Center.
AB - BACKGROUND: In November 2010, the American College of Cardiology Foundation
published revised appropriateness criteria (AC) for cardiac computed tomography
(CT). We evaluated adherence to these criteria by providers of different
subspecialties at a tertiary referral center. METHODS: Reports of 383 consecutive
patients who underwent clinically indicated cardiac CT from December 1, 2010, to
July 31, 2011, were reviewed by physicians with appropriate training in cardiac
CT. Scans were classified as appropriate, inappropriate, or uncertain based on
the revised 2010 AC. Studies that did not fall under any of the specified
indications were labeled as unclassified. Adherence to the AC was also analyzed
as a function of provider type. Research scans were excluded from this analysis.
RESULTS: Three hundred eight exams (80%) were classified as appropriate; 26 (7%),
as inappropriate; 30 (8%), as uncertain; and 19 (5%), as unclassified. Of the 19
(5%) unclassified cardiac CT exams, the most common indication was for evaluation
of suspected aortic dissection. Three hundred five exams (80%) were referred by
cardiologists; 73 (19%), by internists; and 5 (1%), by neurologists. Of the 305
cardiology-referred studies, 221 (73%) were ordered by general cardiologists; 28
(9%), by interventional cardiologists; and 56 (19%), by electrophysiologists.
There was no significant difference in adherence to the criteria between provider
specialties or between cardiology subspecialties (P > 0.05). CONCLUSIONS: high
across provider specialties.
PMID- 25136848
TI - Lymphocyte depletion after alemtuzumab induction disrupts intestinal fungal
microbiota in cynomolgus monkeys.
AB - BACKGROUND: The interactions of specific fungal phylotypes with immune cells have
been recently documented; however, little is known whether gut fungal microbiota
is influenced by aberrant immune response in immunosuppressive state. This study
aimed to define the biologic impact of lymphocyte depletion on gut fungal
microbiota and their relationship. METHODS: Fifteen male cynomolgus monkeys with
CD52 antigen negative on erythrocytes were administered intravenously with a
single dose (3.0 mg kg body weight) of alemtuzumab. Depletion and repopulation of
circulating and mucosal lymphocytes were determined. The dynamic variations of
intestinal fungal microbiota were characterized using 18S ribosomal DNA-based
molecular techniques. RESULTS: The fungal microbiota in colonal mucosa was
perturbed during lymphocyte depletion, characterized by increased diversity and
colonization of Candida albicans, Aspergillus clavatus, and Saccharomyces
cerevisiae. The diversity of the fecal fungal population decreased markedly after
mucosal lymphocyte depletion, and specific fungal phylotypes, especially Candida
albicans, Saccharomyces cerevisiae, and Botryotinia fuckeliana, were expanded
(P<0.05). After reconstitution of mucosal lymphocytes, the composition and
diversity of the gut fungal microbiota were both recovered. A close association
of the community diversity and Candida albicans colonization with T lymphocyte
subsets was also identified. CONCLUSION: Our findings demonstrate that mucosal
lymphocyte depletion leads to the dysbiosis of gut fungal microbiota, suggesting
its role in maintaining host-fungus homeostasis. The pathophysiologic
consequences of this altered fungal colonization might provide novel clues to
uncover the underlying mechanism of enteric fungal infection in immunosuppressive
therapies.
PMID- 25136849
TI - Polyomavirus nephropathy: quantitative urinary polyomavirus-Haufen testing
accurately predicts the degree of intrarenal viral disease.
AB - BACKGROUND: A qualitative highly predictive urinary test for polyomavirus
nephropathy (PVN) is the PV-Haufen test. This article evaluates whether a
quantitative PV-Haufen analysis, that is, the number of PV-Haufen shed per
milliliter urine, predicts PVN disease grades and the severity of intrarenal PV
replication. METHODS: Polyomavirus-Haufen were counted in 40 urine samples from
patients with biopsy-proven definitive PVN. The number of PV-Haufen was
correlated with both histologic PVN disease grades 1 to 3 and the number of SV40
T-expressing cells as indicators of intrarenal PV replication in corresponding
renal allograft biopsies (manual counts and automated morphometry). Findings from
quantitative PV-Haufen analyses were compared to conventional laboratory test
results, that is, BK viremia (quantitative polymerase chain reaction [PCR]) and
BK viruria (quantitative PCR and decoy cell counts). RESULTS: Polyomavirus-Haufen
counts showed excellent correlation (alpha0.77-0.86) with the severity of
intrarenal PV replication and disease grades. In particular, low PV-Haufen
numbers strongly correlated with early PVN grade 1 and minimal intrarenal
expression of SV40-T antigen (P < 0.001). In comparison, BK viremia and viruria
levels by PCR showed only modest correlations with histologic SV40-T expression
(alpha0.40-0.49) and no significant correlation with disease grades or minimal
intrarenal PV replication. No correlations were seen with urinary decoy cell
counts. In contrast to conventional quantitative PCR assays or decoy cell counts,
quantitative urinary PV-Haufen testing accurately reflects the severity of PV
replication, tissue injury, and PVN disease grades. CONCLUSIONS: Quantitative PV
Haufen testing is a novel noninvasive approach to patient management for the
diagnosis and prediction of PVN disease grades and monitoring of disease course
during therapy.
PMID- 25136851
TI - Physicians' Practice of Dispensing Medicines: A Qualitative Study.
AB - OBJECTIVES: The physical act of giving medication to patients to administer away
from a health care setting, dispensing, is normally performed by pharmacists.
Dispensing of medication by physicians is a neglected patient safety issue, and
having observed considerable variation in practice, the lead author sought to
explore this issue further. A literature review yielded zero articles pertaining
to this, so an exploratory study was commenced. The qualitative arm, relating to
junior physicians' experience of, and training in, dispensing, is reported here.
METHODS: Focus groups were conducted to explore the beliefs, ideas, and
experiences of physicians-in-training pertaining to dispensing of medication.
These were recorded and transcribed. The transcriptions were thematically
analyzed using the grounded theory. RESULTS: The emergency department was the
most common site of dispensing. No formal training in dispensing had been
received. Informal training was variable in content and utility. The physicians
felt that dispensing was part of their role. CONCLUSIONS: Despite being expected
to dispense, and the patient safety issues involved in giving drugs to patients
to use at home, physicians do not feel that they have been trained to undertake
this task. These findings from 1 hospital raise questions about the wider quality
and safety of this practice.
PMID- 25136852
TI - Family Satisfaction in Critical Care Units: Does an Open Visiting Hours Policy
Have an Impact?
AB - : For critically ill patients, the interaction between health care providers and
family members is essential in daily decision making. Improving this relationship
has a positive impact on satisfaction with the overall care provided to patients
and reduces family member symptoms of depression, anxiety, and posttraumatic
stress disorder. In this study, we analyzed the impact of visitation policy (open
versus restricted) on family satisfaction using the previously well-validated
Critical Care Family Satisfaction Survey (CCFSS) questionnaire. METHODS: This is
a cross-sectional prospective observational study conducted between November 1,
2009, and January 31, 2010, in 2 critical care units with 2 different visiting
policy systems, unit A (open visiting hours) and B (restricted visiting hours),
comparing family satisfaction in both units using the CCFSS questionnaire.
Responses were grouped in 5 satisfaction constructs, namely, the support
construct, which assesses the degree of satisfaction with the support of the
intensive care staff as perceived by relatives; the assurance construct, which
assesses the degree of satisfaction regarding honest answers being given and the
responder's confidence that the patient is receiving the best care possible; the
proximity construct, which assesses the degree of satisfaction with the physical
and emotional access to the patient; the information construct, which assesses
the degree of satisfaction with the adequacy of information given to relatives;
and the comfort construct, which assesses satisfaction with physical comfort and
amenities. RESULTS: During the study period, 115 questionnaires were distributed
in each of the 2 sites. The response rates in units A and B were 92% (106) and
100% (115), respectively. The mean stay time in the intensive care unit was 3.7
days. There were more trauma cases in unit A and more cardiac patients in unit B.
There was no significant difference between the 2 units in any of the 5
satisfaction constructs, the support, assurance, proximity, information, and
comfort constructs, although there was a nonsignificant trend favoring the unit
with the more liberal visit policy regarding amenities (unit A). CONCLUSIONS: We
concluded that family satisfaction to care provided in intensive care as measured
by the CCFSS questionnaire was not influenced by frequency of visitation among
Saudi families. Factors other than open visiting hours may be important to
evaluate.
PMID- 25136854
TI - Conservation genetics of the Philippine tarsier: cryptic genetic variation
restructures conservation priorities for an island archipelago primate.
AB - Establishment of conservation priorities for primates is a particular concern in
the island archipelagos of Southeast Asia, where rates of habitat destruction are
among the highest in the world. Conservation programs require knowledge of
taxonomic diversity to ensure success. The Philippine tarsier is a flagship
species that promotes environmental awareness and a thriving ecotourism economy
in the Philippines. However, assessment of its conservation status has been
impeded by taxonomic uncertainty, a paucity of field studies, and a lack of
vouchered specimens and genetic samples available for study in biodiversity
repositories. Consequently, conservation priorities are unclear. In this study we
use mitochondrial and nuclear DNA to empirically infer geographic partitioning of
genetic variation and to identify evolutionarily distinct lineages for
conservation action. The distribution of Philippine tarsier genetic diversity is
neither congruent with expectations based on biogeographical patterns documented
in other Philippine vertebrates, nor does it agree with the most recent
Philippine tarsier taxonomic arrangement. We identify three principal
evolutionary lineages that do not correspond to the currently recognized
subspecies, highlight the discovery of a novel cryptic and range-restricted
subcenter of genetic variation in an unanticipated part of the archipelago, and
identify additional geographically structured genetic variation that should be
the focus of future studies and conservation action. Conservation of this
flagship species necessitates establishment of protected areas and targeted
conservation programs within the range of each genetically distinct variant of
the Philippine tarsier.
PMID- 25136856
TI - Short- and long-term effects of ambient ozone and fine particulate matter on the
respiratory health of chronic obstructive pulmonary disease subjects.
AB - To date, no study has evaluated the short- and long-term effects air pollution
exposure on emphysematous subjects who have undergone lung volume reduction
surgery (LVRS). Data from the National Emphysema Treatment Trial study (1998
2003) included 1,218 subjects, aged 39 to 84. Daily values of ambient fine
particulate matter (aerodynamic diameter < 2.5 MUm; PM2.5) and ozone were
obtained. Mixed-effects models tested the association between short- and long
term pollutant concentrations and changes in pulmonary function. Cumulative air
pollution exposure was strongly associated with worsened respiratory function and
symptoms. Mean PM2.5 was associated with poorer lung function. Lagged exposures
were poorly associated with respiratory health outcomes. There were detrimental
respiratory and pulmonary effects observed in response to even low levels of
ambient air pollutants among study participants. These results are indicative
that exposures even below those of air quality standards may still pose
significant risks to severe chronic obstructive pulmonary disease (COPD)
subjects.
PMID- 25136855
TI - A canonical circuit for generating phase-amplitude coupling.
AB - 'Phase amplitude coupling' (PAC) in oscillatory neural activity describes a
phenomenon whereby the amplitude of higher frequency activity is modulated by the
phase of lower frequency activity. Such coupled oscillatory activity--also
referred to as 'cross-frequency coupling' or 'nested rhythms'--has been shown to
occur in a number of brain regions and at behaviorally relevant time points
during cognitive tasks; this suggests functional relevance, but the circuit
mechanisms of PAC generation remain unclear. In this paper we present a model of
a canonical circuit for generating PAC activity, showing how interconnected
excitatory and inhibitory neural populations can be periodically shifted in to
and out of oscillatory firing patterns by afferent drive, hence generating higher
frequency oscillations phase-locked to a lower frequency, oscillating input
signal. Since many brain regions contain mutually connected excitatory-inhibitory
populations receiving oscillatory input, the simplicity of the mechanism
generating PAC in such networks may explain the ubiquity of PAC across diverse
neural systems and behaviors. Analytic treatment of this circuit as a nonlinear
dynamical system demonstrates how connection strengths and inputs to the
populations can be varied in order to change the extent and nature of PAC
activity, importantly which phase of the lower frequency rhythm the higher
frequency activity is locked to. Consequently, this model can inform attempts to
associate distinct types of PAC with different network topologies and
physiologies in real data.
PMID- 25136859
TI - Amino acid-based zwitterionic polymers: antifouling properties and low
cytotoxicity.
AB - A group of five amino acid containing zwitterionic vinyl monomers, based on
serine, lysine, ornithine, glutamic acid, and aspartic acid, respectively, were
proposed and developed for potential antifouling applications. Their polymer
brushes were grafted on gold chips by surface-initiated photoiniferter-mediated
polymerization. We then compared their performance in resisting protein
adsorption from full human serum and plasma. All five polymers can reduce protein
adsorption by more than 90% compared to the unmodified gold. The ornithine-based
and aspartic acid-based poly(methacrylamide) can most strongly resist protein
adsorption from serum and plasma, compared to the other three. The ability of
surfaces to suppress bacterial adhesion is another criterion in evaluating
antifouling properties of materials. Our results show that the five polymer
grafted surfaces can significantly suppress Escherichia coli K12 adhesion to 99%
compared to the bare gold surface. The zwitterionic structure of amino acids,
with homogenously distributed and balanced positive and negative charges, is
responsible for the outstanding antifouling properties. Considering multiple
potential applications (e.g. medical devices and drug delivery) of the
antifouling materials, we further systematically evaluated the cytotoxicity of
both monomers and polymer nanogels for all five materials at various
concentrations. Very low cytotoxicity was observed for all tested amino acid
based monomers and nanogels, which is comparable or even lower than the
traditional and some newly developed antifouling materials, which might be
related to the biomimetic nature of amino acids.
PMID- 25136857
TI - Erythrocyte-derived microparticles supporting activated protein C-mediated
regulation of blood coagulation.
AB - Elevated levels of erythrocyte-derived microparticles are present in the
circulation in medical conditions affecting the red blood cells. Erythrocyte
derived microparticles expose phosphatidylserine thus providing a suitable
surface for procoagulant reactions leading to thrombin formation via the tenase
and prothrombinase complexes. Patients with elevated levels of circulating
erythrocyte-derived microparticles have increased thrombin generation in vivo.
The aim of the present study was to investigate whether erythrocyte-derived
microparticles are able to support the anticoagulant reactions of the protein C
system. Erythrocyte-derived microparticles were isolated using
ultracentrifugation after incubation of freshly prepared erythrocytes with the
ionophore A23187 or from outdated erythrocyte concentrates, the different
microparticles preparations yielding similar results. According to flow cytometry
analysis, the microparticles exposed phoshatidylserine and bound lactadherin,
annexin V, and protein S, which is a cofactor to activated protein C. The
microparticles were able to assemble the tenase and prothrombinase complexes and
to stimulate the formation of thrombin in plasma-based thrombin generation assay
both in presence and absence of added tissue factor. The addition of activated
protein C in the thrombin generation assay inhibited thrombin generation in a
dose-dependent fashion. The anticoagulant effect of activated protein C in the
thrombin generation assay was inhibited by a monoclonal antibody that prevents
binding of protein S to microparticles and also attenuated by anti-TFPI
antibodies. In the presence of erythrocyte-derived microparticles, activated
protein C inhibited tenase and prothrombinase by degrading the cofactors FVIIIa
and FVa, respectively. Protein S stimulated the Arg306-cleavage in FVa, whereas
efficient inhibition of FVIIIa depended on the synergistic cofactor activity of
protein S and FV. In summary, the erythrocyte-derived microparticle surface is
suitable for the anticoagulant reactions of the protein C system, which may be
important to balance the initiation and propagation of coagulation in vivo.
PMID- 25136860
TI - Chemically modified peptide scaffolds target the CFTR-associated ligand PDZ
domain.
AB - PDZ domains are protein-protein interaction modules that coordinate multiple
signaling and trafficking pathways in the cell and that include active
therapeutic targets for diseases such as cancer, cystic fibrosis, and addiction.
Our previous work characterized a PDZ interaction that restricts the apical
membrane half-life of the cystic fibrosis transmembrane conductance regulator
(CFTR). Using iterative cycles of peptide-array and solution-binding analysis, we
targeted the PDZ domain of the CFTR-Associated Ligand (CAL), and showed that an
engineered peptide inhibitor rescues cell-surface expression of the most common
CFTR disease mutation DeltaF508. Here, we present a series of scaffolds
containing chemically modifiable side chains at all non-motif positions along the
CAL PDZ domain binding cleft. Concordant equilibrium dissociation constants were
determined in parallel by fluorescence polarization, isothermal titration
calorimetry, and surface plasmon resonance techniques, confirming robust affinity
for each scaffold and revealing an enthalpically driven mode of inhibitor
binding. Structural studies demonstrate a conserved binding mode for each
peptide, opening the possibility of combinatorial modification. Finally, we
diversified one of our peptide scaffolds with halogenated substituents that
yielded modest increases in binding affinity. Overall, this work validates our
approach and provides a stereochemical foundation for further CAL inhibitor
design and screening.
PMID- 25136861
TI - Ire1 mediated mRNA splicing in a C-terminus deletion mutant of Drosophila Xbp1.
AB - The Unfolded Protein Response is a homeostatic mechanism that permits eukaryotic
cells to cope with Endoplasmic Reticulum (ER) stress caused by excessive
accumulation of misfolded proteins in the ER lumen. The more conserved branch of
the UPR relies on an ER transmembrane enzyme, Ire1, which, upon ER stress,
promotes the unconventional splicing of a small intron from the mRNA encoding the
transcription factor Xbp1. In mammals, two specific regions (the hydrophobic
region 2--HR2--and the C-terminal translational pausing site) present in the
Xbp1unspliced protein mediate the recruitment of the Xbp1 mRNA-ribosome-nascent
chain complex to the ER membrane, so that Xbp1 mRNA can be spliced by Ire1. Here,
we generated a Drosophila Xbp1 deletion mutant (Excision101) lacking both HR2 and
C-terminal region, but not the Ire1 splicing site. We show that Ire1-dependent
splicing of Xbp1 mRNA is reduced, but not abolished in Excision101. Our results
suggest the existence of additional mechanisms for ER membrane targeting of Xbp1
mRNA that are independent of the C-terminal domain of Drosophila Xbp1unspliced.
PMID- 25136862
TI - MicroRNA-410 suppresses migration and invasion by targeting MDM2 in gastric
cancer.
AB - Gastric cancer is one of the most frequent malignancies in tumors in the East
Asian countries. Identifying precise prognostic markers and effective therapeutic
targets is important in the treatment of gastric cancer. microRNAs (miRNAs) play
important roles in tumorigenesis. However, the mechanisms by which miRNAs
regulate gastric cancer metastasis remain poorly understood. In this study, we
found that the levels of miR-410 in gastric cancer and cell lines were much lower
than that in the normal control, respectively, and the lower level of miR-410 was
significantly associated with lymph-node metastasis. Transfection of miR-410
mimics could significantly inhibit the cell proliferation, migration and invasion
in the HGC-27 gastric cancer cell lines. In contrast, knockdown of miR-410 had
the opposite effect on the cell proliferation, migration and invasion. Moreover,
we also found that MDM2 was negatively regulated by miR-410 at the post
transcriptional level, via a specific target site with the 3'UTR by luciferase
reporter assay. The expression of MDM2 was inversely correlated with miR-410
expression in gastric cancer tissues, and overexpression of MDM2 in miR-410
transfected gastric cancer cells effectively rescued the inhibition of cell
proliferation and invasion caused by miR-410. Thus, our findings suggested that
miR-410 acted as a new tumor suppressor by targeting the MDM2 gene and inhibiting
gastric cancer cells proliferation, migration and invasion. The findings of this
study contributed to the current understanding of these functions of miR-410 in
gastric cancer.
PMID- 25136863
TI - Superior laryngeal nerve injury: effects, clinical findings, prognosis, and
management options.
AB - PURPOSE OF REVIEW: The superior laryngeal nerve (SLN) provides motor innervation
to the cricothyroid muscle. However, the functions of this muscle and the
anatomic variations of the nerve that supplies it are not fully understood. SLN
paresis and paralysis (SLNp) is difficult to diagnose because of a lack of
consistent laryngeal findings, and its effects on the voice likely go beyond
simple pitch elevation control. RECENT FINDINGS: Although SLNp has traditionally
been thought to lead to voice pitch limitation, recent research findings reveal
multiple roles for this nerve in voice and speech. Cricothyroid muscles are the
primary controls of fundamental frequency of voice. SLNp can lead to significant
contraction of pitch range, vocal fold vibratory phase asymmetry, and acoustic
aperiodicity, thus leading to an overall poor vocal quality. In addition,
cricothyroid muscles may also play a role in pitch lowering and shifting from
voiced to unvoiced sounds during speech. SUMMARY: Subtle signs, symptoms, and
diagnostic findings associated with SLNp make this disorder difficult to
characterize clinically. Lack of treatment methodologies to restore the dynamic
action of the cricothyroid muscles poses difficulties in treating patients with
this condition. A more thorough understanding of the effects of SLNp will improve
diagnosis and treatment.
PMID- 25136865
TI - A perspective on the evolution of distal radius fracture treatment.
PMID- 25136866
TI - En bloc joystick reduction of a comminuted intra-articular distal radius
fracture: a technical trick.
AB - A patient with a 1-month-old intra-articular distal radius fracture (treated
closed in a splint) presented with an unacceptable degree of pain and stiffness
caused by shortening and dorsal angulation of the distal radius. The fracture was
comminuted with 4 or 5 distinct fragments, several involving the articular
surface. Surgical correction was attempted. During the procedure, it was noted
that, though the distal radius was shortened and angulated, there was actually
acceptable congruity of the articular surface itself, despite the intra-articular
nature of the fracture. Bone quality was poor and healing incomplete. Thus, we
were concerned the currently congruous articular surface would fall apart with
manipulation. Given this situation, we used a unique scaffolding technique with
Kirschner wires placed in perpendicular fashion to both hold the articular
surface intact and manipulate it en bloc. This technique is a simple way to turn
a complex fracture into an easily reduced 2-part fracture.
PMID- 25136864
TI - In vitro inflammation inhibition model based on semi-continuous toll-like
receptor biosensing.
AB - A chemical inhibition model of inflammation is proposed by semi-continuous
monitoring the density of toll-like receptor 1 (TLR1) expressed on mammalian
cells following bacterial infection to investigate an in vivo-mimicked drug
screening system. The inflammation was induced by adding bacterial lysate (e.g.,
Pseudomonas aeruginosa) to a mammalian cell culture (e.g., A549 cell line). The
TLR1 density on the same cells was immunochemically monitored up to three cycles
under optimized cyclic bacterial stimulation-and-restoration conditions. The
assay was carried out by adopting a cell-compatible immunoanalytical procedure
and signal generation method. Signal intensity relative to the background control
obtained without stimulation was employed to plot the standard curve for
inflammation. To suppress the inflammatory response, sodium salicylate, which
inhibits nuclear factor-kappaB activity, was used to prepare the standard curve
for anti-inflammation. Such measurement of differential TLR densities was used as
a biosensing approach discriminating the anti-inflammatory substance from the non
effector, which was simulated by using caffeic acid phenethyl ester and
acetaminophen as the two components, respectively. As the same cells exposed to
repetitive bacterial stimulation were semi-continuously monitored, the efficacy
and toxicity of the inhibitors may further be determined regarding persistency
against time. Therefore, this semi-continuous biosensing model could be
appropriate as a substitute for animal-based experimentation during drug
screening prior to pre-clinical tests.
PMID- 25136867
TI - Volar plate capsulodesis for metacarpophalangeal hyperextension with basal joint
arthritis.
AB - Basal joint arthritis leads to thumb metacarpophalangeal (MCP) hyperextension
that may prevent physiologic pinch. Various techniques have been used to address
this hyperextension, but most are technically challenging, time-consuming, and
not supported by long-term follow-up results. Furthermore, few groups have
reported subjective, patient-based outcomes after such procedures. In a
retrospective study, we evaluated a cohort of 14 patients who underwent a novel
technique of thumb MCP capsulodesis in conjunction with basal joint arthroplasty.
A mean of 4.74 years after surgery, subjective outcome measures (Disabilities of
the Arm, Shoulder, and Hand questionnaire; visual analog scale for pain; patient
satisfaction) and objective outcome measures (range of motion, grip and pinch
strengths) all reflected excellent function. The described technique for MCP
capsulodesis is an attractive adjunct to basal joint arthroplasty, but further
prospective studies are needed to establish specific operative indications.
PMID- 25136868
TI - Online ratings of orthopedic surgeons: analysis of 2185 reviews.
AB - Online ratings of orthopedic surgeons have not been studied. We conducted a study
to evaluate the online ratings of orthopedic surgeons in a major metropolitan
region, to identify trends in ratings of orthopedic surgeons, and to analyze
ratings to identify variables of significance in determining overall rating.
Website traffic was used to identify the 8 busiest physician rating websites:
AngiesList.com, EverydayHealth.com, Thirdage.com, Yelp.com, HealthGrades.com,
Vitals.com, UCompareHealthcare.com, and RateMDs.com. These websites were
consulted for data regarding orthopedic surgeons in a major metropolitan region
with a population of 1.3 million in September 2012. Surgeon ratings were scaled
from 0 to 100 for homogeneity. Of the 8 websites considered, 4 were excluded
because of inaccessible or unreliable data. The qualifying sites were
HealthGrades.com, Vitals.com, UCompareHealthcare.com, and RateMDs.com, with 2185
reviews total. Across these websites, mean overall rating of orthopedic surgeons
was 81.8 (between 100, definitely recommend, and 80, mostly recommend). Five
variables were statistically significant (Ps < .01) for higher ratings: ease of
scheduling, time spent with patient, wait time, surgeon proficiency/knowledge,
and bedside manner.
PMID- 25136869
TI - Arthroscopic anterior shoulder stabilization with percutaneous assistance and
posteroinferior capsular plication.
AB - To study the technique and clinical outcomes of arthroscopic shoulder
stabilization with anterior labral repair and percutaneous posteroinferior
capsular plication, we retrospectively reviewed 20 cases. Mean (SD) final
postoperative follow-up was 3.4 (0.6) years (range, 2.7-5.1 years). A mean (SD)
of 4.9 (0.9) suture anchors (range, 4-7) was used during surgery, with 1.6 (0.7)
(range, 1-3) devoted to the posteroinferior plication. There were statistically
significant improvements in forward elevation (P = .016) and internal rotation (P
= .018) from before surgery to final postoperative follow-up; external rotation
did not change (P = .336). Significant improvements (P < .001) were also seen in
visual analog scale pain ratings, American Shoulder and Elbow Surgeons survey
scores, and Simple Shoulder Test scores. Mean (SD) Rowe instability score at
final follow-up was 81.1 (28.9). Eighty-five percent of the patients returned to
sport at or above preinjury level, and 70% returned to a degree of athletic
physical contact at or above preinjury level. Two cases (10%) were categorized as
treatment failures (redislocation). Percutaneously assisted arthroscopic anterior
stabilization with posteroinferior capsular plication produces acceptable
results, with functional outcomes and redislocation rates comparable to those
reported in the literature.
PMID- 25136870
TI - The normal patella--does it exist? A histologic analysis.
AB - It is unclear if healthy-appearing patellae in patients having total knee
arthroplasty (TKA) can be selectively retained. In the study reported here, we
hypothesized that grossly normal-appearing patellae in TKA candidates would show
significant evidence of microscopic degeneration and thinning of the articular
cartilage. Ninety-six consecutive patients (110 knees) with primary degenerative
osteoarthritis were recruited from a single institution between November 2010 and
June 2011. Thirteen patellae (11 patients) had grossly normal-appearing
cartilage. A pathologist measured patellar cartilage thickness in each quadrant
and evaluated for evidence of microscopic degenerative change. Mean cartilage
thickness was 2.35 mm (range, 1.0-3.0 mm) for superomedial quadrant, 2.31 mm
(range, 1.5-3.0 mm) for superolateral quadrant, 2.31 mm (range, 1.0-4.0 mm) for
inferomedial quadrant, and 2.62 mm (range, 1.5-3.5 mm) for inferolateral
quadrant. Four-point mean (SD) was 2.39 (0.79) mm. Each patella demonstrated at
least 2 of the predefined histologic markers of degeneration: fibrillation,
fibrosis, chondrocyte proliferation, cyst formation, and fissuring and/or
thinning. Even healthy-appearing patellae on gross examination have clear
histologic markers of early to moderate articular degeneration. Further
comparisons of cartilage thickness using area measurements are needed before the
significance of the effect of this deterioration on the technique of selective
patellar retention during TKA can be known.
PMID- 25136871
TI - Nonaccidental traumatic dislocation of the hip in a 3-year-old child: a report of
a rare pediatric injury.
AB - Traumatic hip dislocations are rare in children, and reports of these injuries
focus primarily on the risk of osteonecrosis of the femoral head as well as the
long-term efficacy of treatment. Anatomical characteristics of the hip in young
children, such as ligamentous laxity and a pliable acetabulum, can allow hip
dislocation with low-energy trauma, but these injuries occur primarily in school
aged children during play activities. We report a hip dislocation in a 3-year-old
child with no clear explanation of the mechanism of injury and with multiple
unexplained bruises at different stages of healing that led to the diagnosis of
nonaccidental trauma (NAT). This case highlights the need to consider NAT in
young patients with a traumatic hip dislocation.
PMID- 25136872
TI - Snapping knee caused by symptomatic fabella in a native knee.
AB - We report a case of a 31-year-old man with a 5-year history of snapping knee
syndrome secondary to a single, large symptomatic fabella of the knee. On
physical examination, the patient was able to reproduce an audible and palpable
snapping with active range of motion. His condition was refractory to physical
therapy. He had undergone a prior iliotibial band release at an outside facility.
After excision of the fabella, measuring 15 * 8 * 9 mm, the patient's snapping
and pain with activity were resolved.
PMID- 25136873
TI - Effects of corticosteroid injection on nerve conduction testing for the diagnosis
of carpal tunnel syndrome.
AB - We conducted a study to determine the change in nerve conduction testing after
steroid injection in patients with carpal tunnel syndrome (CTS). One hundred
forty-five patients with suspected CTS were targeted for this study. Twenty-seven
patients underwent testing before and after injection. Repeat studies were
performed 4 to 6 weeks after injection. All data from the electrodiagnostic
studies were entered into a database and used for comparison. Before injection,
mean (SD) distal motor latency (DML) was 5.01 (0.9) ms, and mean (SD) peak
sensory latency (PSL) was 5.01 (0.88) ms. After injection, mean (SD) DML was 4.82
(0.7) ms, and mean (SD) PSL was 4.69 (0.66) ms. Mean (SD) difference between
preinjection and postinjection DML was 0.187 (0.45) ms, and mean difference
between preinjection and postinjection PSL was 0.319 (0.48) ms. Both differences
were statistically significant (paired t test). Our study results showed a
statistical difference between testing done before and after steroid injection.
These results indicate that injections given before electrodiagnostic testing
alter results and may affect patient management.
PMID- 25136874
TI - Critical review of patient education materials from the American Academy of
Orthopaedic Surgeons.
AB - We performed an expanded readability analysis to determine if the American
Academy of Orthopaedic Surgeons, AAOS, had sufficiently improved its patient
education materials since they were originally studied in 2007. In March 2013, we
downloaded patient education materials from the AAOS patient information website,
Your Orthopaedic Connection. Using 10 different readability formulas, we found
that the mean grade level of patient education materials on the website is 8.84.
Flesch-Kincaid analysis showed a mean grade level of 9.98, range, 6.6-12.6. Nine
other readability analyses showed a mean reading level of 7.7, range, 6.5-13.7.
Although this is an improvement over the 2007 level, it is above the average
national reading comprehension level. The readability of patient education
materials on the AAOS website still exceeds the average reading ability of a US
adult. Revisions made over the 5 years leading up to this latest study resulted
in better readability. The Prevention and Safety entries, written near seventh
grade level, should serve as a model for the remaining articles.
PMID- 25136875
TI - Do practice settings influence defensive medicine in orthopedic surgery?
AB - Defensive medicine is often practiced out of fear of legal liability. We
conducted a study to compare the costs of defensive medicine among US orthopedic
surgeons by practice type and American Medical Association (AMA) state medical
liability classification. Two thousand surgeons registered with the American
Academy of Orthopaedic Surgeons were sent a survey on defensive medicine. Costs
were analyzed using 2011 Centers for Medicare and Medicaid Services data. Of the
2000 surgeons, 1214 (61%) completed the survey. Results showed that defensive
tests were ordered by a higher proportion of nonacademic physicians than academic
physicians in all 8 categories of orthopedic care, with a mean difference of
$2348 in monthly defensive expenditures between groups. A higher rate of
defensive testing by orthopedists in AMA crisis states versus safe states was
also observed in 6 of the 8 areas of care studied, with mean monthly defensive
expenditures ranging from $9208 in crisis states to $6596 in safe states.
Defensive orthopedics contributes significantly to health care costs, with
marginal benefit to patients-especially in nonacademic and crisis-state
orthopedics practices.
PMID- 25136876
TI - Disseminated coccidioidomycosis of the spine in an immunocompetent patient.
AB - Coccidioidomycosis infections result from inhalation of the dimorphic fungus
Coccidiodes immitis. Coccidioidomycosis typically is benign, but its extremely
rare disseminated form can result in significant morbidity and mortality.
Dissemination of the fungus to the spine is difficult to control and usually
requires an aggressive combination approach (surgical/medical). In this article,
we report the case of a 27-year-old Indonesian man with vertebral osteomyelitis
caused by disseminated coccidioidomycosis. We outline the case management
(includes 30-month follow-up) and review the treatment recommendations. The
patient presented with an unstable C5 pathologic fracture caused by C immitis.
After corpectomy and stabilization of the cervical spine along with antifungal
therapy with amphotericin B and oral fluconazole, he developed multiple
complications. This case illustrates some of the potential pitfalls in managing
spinal osteomyelitis caused by C immitis and the need for continuous medical
therapy after surgical treatment.
PMID- 25136877
TI - Bladder tear during revision total hip arthroplasty.
AB - Total hip arthroplasty (THA) and revision total hip arthroplasty are among the
most commonly performed orthopedic procedures. There are many reported
complications of THA, but intrapelvic complications are a rare subset. Bladder
injuries have infrequently been described in association with this common
procedure. We present an unusual case of a bladder tear occurring
intraoperatively during a revision THA. It is suspected that the patient's
history of multiple prior hip procedures caused adhesions of the bladder to the
pelvic floor and predisposed the bladder to injury during acetabular revision.
Previous reports of bladder injury relating to THA have described thermal
necrosis, component migration, and occasional direct perforation. There are no
prior case reports describing bladder tears related to adhesions occurring
intraoperatively during revision THA. This case report highlights the importance
of surgeon awareness of an unusual complication. In this case, intraoperative and
postoperative recognition of a hematuria diagnosis led to the appropriate
treatment, and this patient had an acceptable outcome.
PMID- 25136878
TI - The business side of medicine for orthopedic residents and fellows: when were we
supposed to learn this?
AB - CPT, CMS, RAC, ICD-10, ACA, RVU, ACO-these are a few of the 3-letter acronyms I
find myself swimming in while completing my final years of orthopedic training.
It has suddenly become clear that this aspect of my future career, the business
side, has lacked appropriate preparation. From countless hours buried in
textbooks as a first-year medical student to late nights in the operating room as
a fellow, I realize that I have had no formal business training, not even a
single course, while nearing the completion of, effectively, the 28th grade. All
while just days away from running my own business-my clinical practice as an
orthopedic surgeon.
PMID- 25136879
TI - Cystatin C and risk of mortality among patients undergoing percutaneous coronary
intervention.
AB - AIMS: We tested the prognostic value of cystatin C in patients with documented
coronary artery disease (CAD) who underwent percutaneous coronary artery
intervention (PCI). We also tested the hypothesis that the incremental predictive
value of cystatin C on all-cause mortality was superior to that of glomerular
filtration rate (GFR) by the Modification of Diet in Renal Disease (MDRD)
formula. METHODS AND RESULTS: Included in the study were 2,757 patients (mean age
63 years, 77% men). Blood samples for cystatin C levels were collected
immediately before PCI. During a median follow-up of two years, 114 patients
died. In multivariable Cox analyses, after adjustment for several confounders,
GFR (p=0.004) and cystatin C concentration (p<0.0001) were independent predictors
of all-cause death. Cystatin C predicted all-cause death (c-statistic: 0.794)
better than GFR estimate based on creatinine (c-statistic: 0.776, p=0.008 for
comparison), and significantly reclassified 15% of patients into categories that
reflected their actual likelihood of death more accurately (p=0.005). Adding
cystatin C and GFR in the same multivariable survival model, only cystatin C
level was a significant predictor of death. CONCLUSIONS: This study presents for
the first time the incremental predictive value of cystatin C over the creatinine
based MDRD formula on all-cause mortality for CAD patients undergoing PCI.
PMID- 25136880
TI - Impact of frailty on short- and long-term morbidity and mortality after
transcatheter aortic valve implantation: risk assessment by Katz Index of
activities of daily living.
AB - AIMS: Transcatheter aortic valve implantation (TAVI) represents a less invasive
treatment option for elderly patients. Therefore, we aimed to determine the
impact of frailty measured by the Katz Index of activities of daily living (ADL)
on short- and long-term mortality after TAVI. METHODS AND RESULTS: Our study
included 300 consecutive patients (mean age, 82+/-5 years) who had undergone TAVI
at our institution (158 transapical, 142 transfemoral procedures). At baseline,
144 patients were impaired in at least one ADL and therefore defined as frail
(Katz Index <6). Regarding in-hospital outcome, all serious complications except
for stage 3 acute kidney injury were equally distributed in both groups, but
early mortality was significantly higher in frail persons (5.5% vs. 1.3%, p=0.04
for immediate procedural mortality; 17% vs. 5.8%, p=0.002 for 30-day mortality;
and 23% vs. 6.4%, p<0.0001 for procedural mortality). The risk-score-based 30-day
mortality estimates (29% vs. 24% for log. EuroSCORE I, 9.5% vs. 7.5% for
EuroSCORE II, and 8.8% vs. 5.9% for STS score) reflected neither the observed 30
day mortality in both groups nor the threefold risk elevation in frail patients.
In contrast, the Katz Index <6 was identified as a significant independent
predictor of long-term all-cause mortality by multivariate analysis (HR 2.67 [95%
CI: 1.7-4.3], p<0.0001). During follow-up (median observation period 537 days)
56% of frail vs. 24% of non-frail patients died. CONCLUSIONS: Frailty status
measured by the Katz Index represents a powerful predictor of adverse early and
late outcome after TAVI, whereas commonly used risk scores lack calibration and
discrimination in a TAVI-specific patient cohort. Therefore, we propose the
incorporation of this simple and reproducible measure into pre-TAVI risk
assessment.
PMID- 25136881
TI - Immediate multivessel percutaneous coronary intervention versus culprit lesion
intervention in patients with acute myocardial infarction complicated by
cardiogenic shock: results of the ALKK-PCI registry.
AB - AIMS: Current guidelines recommend immediate multivessel percutaneous coronary
intervention (PCI) in patients with cardiogenic shock, despite the lack of
randomised trials. We sought to investigate the use and impact on outcome of
multivessel PCI in current practice in cardiogenic shock in Germany. METHODS AND
RESULTS: Between January 2008 and December 2011 a total of 735 consecutive
patients with acute myocardial infarction, cardiogenic shock and multivessel
coronary artery disease underwent immediate PCI in 41 hospitals in Germany. Of
these, 173 (23.5%) patients were treated with immediate multivessel PCI. The
acute success of PCI with respect to TIMI 3 flow did not differ between the
groups (82.5% versus 79.6%). In-hospital mortality with multivessel PCI and
culprit lesion PCI was 46.8% and 35.8%, respectively. In multivariate analysis
multivessel PCI was associated with an increased mortality (odds ratio 1.5; 95%
confidence interval 1.15-1.84). CONCLUSIONS: In current clinical practice in
Germany multivessel PCI is used only in one quarter of patients with cardiogenic
shock treated with primary PCI. We observed an adverse effect of immediate
multivessel PCI. Therefore, a randomised trial is needed to determine the
definitive role of multivessel PCI in cardiogenic shock.
PMID- 25136882
TI - Prognostic impact of multivessel versus culprit vessel only percutaneous
intervention for patients with multivessel coronary artery disease presenting
with acute coronary syndrome.
AB - AIMS: To determine whether multivessel (MV) percutaneous coronary intervention
(PCI) performed in one procedure improves outcomes when compared to single-vessel
(SV) PCI for the culprit lesion(s) in patients with non-ST-segment elevation
acute coronary syndromes (NSTE-ACS). METHODS AND RESULTS: We utilised the Acute
Catheterisation and Urgent Intervention Triage StrategY (ACUITY) study database
to analyse the outcomes of 2,255 patients with MV disease who underwent SV PCI
compared to 609 patients who underwent MV PCI in the setting of NSTE-ACS. The
primary endpoint was the one-year rate of major adverse cardiac events (MACE):
death from any cause, myocardial infarction (MI), or ischaemia-driven
revascularisation. At one year, patients undergoing MV PCI compared to SV PCI had
similar rates of MACE (24.1% vs. 21.7%, respectively, p=0.11). However, death/MI
was significantly higher in the MV PCI group (15.7% vs. 12.6%, p=0.05), primarily
driven by higher rates of periprocedural non-Q-wave MI. Rates of death, ischaemia
driven revascularisation, stent thrombosis, acute renal failure and major
bleeding were similar in both groups. By multivariable analysis with propensity
score adjustment, MV PCI was not an independent predictor of one-year MACE
(HR=1.22; 95% confidence interval [CI]: 0.96, 1.55; p=0.12) or death/MI (HR=1.28;
95% CI: 0.95, 1.74; p=0.15). CONCLUSIONS: In patients with NSTE-ACS and MV
disease, MV PCI does not appear to provide a clear clinical benefit over SV PCI.
Randomised clinical trials specifically addressing these two strategies in this
population, with attention to quality of life and symptom relief, are warranted.
PMID- 25136883
TI - A first-in-man clinical evaluation of Ultimaster, a new drug-eluting coronary
stent system: CENTURY study.
AB - AIMS: To report the six-month angiographic and two-year clinical outcome data
from the first-in-man study with the Ultimaster DES, a thin-strut cobalt-chromium
sirolimus-eluting stent (SES) with an innovative abluminal-gradient-coated
bioresorbable polymer. METHODS AND RESULTS: CENTURY is a multicentre, single-arm,
prospective study that enrolled 105 patients (113 lesions) with coronary artery
disease. All patients were scheduled to have an angiographic follow-up at six
months, while 45 and 20 patients respectively had IVUS and OCT assessments. The
primary endpoint was six-month in-stent late lumen loss. Secondary endpoints
included clinical, IVUS and OCT outcomes. Clinical follow-up is available up to
two years and will continue up to five years. Procedural success was 97.1% and
device success was 100%. Angiographic late loss at six months was 0.04+/-0.35 mm,
also reflected in a low binary restenosis rate of 0.9% and confirmed by IVUS
assessed neointimal volume obstruction of 1.02+/-1.62%. The mean strut coverage
assessed by OCT was 96.2% with 1.66+/-4.02 malapposed stent struts. There were no
deaths in the study, three (2.9%) periprocedural and one (0.9%) spontaneous
myocardial infarction, not related to the target vessel. At one and two years,
the target lesion failure rate was 3.8% and 5.7%, while the TLR rate was 1.9% and
2.8%, respectively. There was one acute definite stent thrombosis. CONCLUSIONS:
The UltimasterTM novel bioresorbable polymer sirolimus-eluting stent demonstrated
good performance, including high procedural success and strong suppression of
neointimal proliferation at six months. Good safety and effectiveness were shown
up to two years in the studied population.
PMID- 25136884
TI - Three-year clinical outcome in the Primary Stenting of Totally Occluded Native
Coronary Arteries III (PRISON III) trial: a randomised comparison between
sirolimus-eluting stent implantation and zotarolimus-eluting stent implantation
for the treatment of total coronary occlusions.
AB - AIMS: Sirolimus-eluting stents (SES) have been shown to be superior to Endeavor
zotarolimus-eluting stents (ZES) and comparable to Resolute ZES at eight-month
angiography in patients treated for total coronary occlusions (TCO). This study
investigated clinical outcome at three-year follow-up. METHODS AND RESULTS: The
PRISON III trial investigated the efficacy and safety of SES against ZES
(Endeavor and Resolute) in two study phases. In the first phase, 51 patients were
randomised to receive SES and 46 to Endeavor ZES. In the second phase, 103 and
104 patients were randomised to SES or Resolute ZES, respectively. Between one
and three years there were only a few additional clinical events in all groups.
As a result, the rates of target lesion revascularisation 12.2% vs. 19.6%,
p=0.49, target vessel failure 14.3% vs. 19.6%, p=0.68, and definite or probable
stent thrombosis 4.1% vs. 2.2% were comparable between SES and Endeavor ZES at
three years. In the second study phase, the rates of target lesion
revascularisation 10% vs. 5.9%, p=0.42, target vessel failure 10% vs. 7.9%,
p=0.79 and definite or probable stent thrombosis 1.0% vs. 0% were similar between
SES and Resolute ZES. CONCLUSIONS: The present study demonstrated a low incidence
of clinical events between one- and three-year follow-up with either SES compared
to Endeavor ZES or SES versus Resolute ZES in patients treated for total coronary
occlusions.
PMID- 25136885
TI - Initial experience and clinical evaluation of the Absorb bioresorbable vascular
scaffold (BVS) in real-world practice: the AMC Single Centre Real World PCI
Registry.
AB - AIMS: To report procedural and midterm clinical outcomes after the use of the
second-generation Absorb everolimus-eluting bioresorbable vascular scaffold
(Absorb BVS) in a real-world percutaneous coronary intervention (PCI) registry.
METHODS AND RESULTS: All patients assigned to treatment with the Absorb BVS in
the Academic Medical Center, Amsterdam, between August 2012 and August 2013 were
included in a prospective registry. A total of 135 patients were included in the
study, including 53 (39%) acute coronary syndrome (ACS) patients (13% ST-segment
elevation myocardial infarction [STEMI]). In total 159 lesions were treated,
including 102 (62%) with a type B2 or C classification. Pre- and post-procedural
quantitative coronary angiography (QCA) analyses showed an acute gain of 1.37+/
0.53 mm. An angiographic success rate was achieved in 152 (96%) of the lesions.
Six-month follow-up was available in 97% of the patients. Six-month cumulative
target vessel failure (composite of all-cause mortality, any myocardial
infarction [MI] and target vessel revascularisation [TVR]) rate was 8.5%,
including a 3.0% MI, 3.0% definite scaffold thrombosis, 6.3% target lesion
revascularisation, and an 8.5% TVR rate. CONCLUSIONS: The use of the Absorb BVS
in a cohort reflecting daily clinical practice is feasible and associated with
good procedural safety and angiographic success rate. In addition, six-month
follow-up is associated with acceptable clinical outcomes.
PMID- 25136886
TI - Severe infective endocarditis after MitraClip implantation treated by cardiac
surgery.
AB - AIMS: To report the first described case of a mitral valve infective endocarditis
(IE) post MitraClip(r). METHODS AND RESULTS: An 88-year-old patient at high
surgical risk (log. EuroSCORE 30.4%) underwent a MitraClip procedure for severe
eccentric organic mitral regurgitation (MR) due to prolapse with a flail leaflet
of the P2 segment (flail gap 6 mm). After one month, the patient was readmitted
to our department for fever and recurrence of shortness of breath. An
echocardiogram demonstrated severe MR recurrence due to ulceration in the region
of the posterior leaflet despite good insertion of both clips, and a large
vegetation of 1513 mm within the clip region. Blood cultures were positive for
staphylococcus aureus. The patient was treated by cardiac surgery with mitral
valve replacement due to IE despite a very high logistic EuroSCORE of 56.8%.
Histological and bacteriological analysis of the clip devices confirmed active
IE. After cardiac surgery, transthoracic echocardiography showed no mitral
regurgitation and a mean gradient across the mitral valve bioprosthesis of about
5 mmHg. The patient was discharged to a rehabilitation department 15 days after
cardiac surgery. CONCLUSIONS: Surgical treatment as bail-out therapy for MR
recurrence secondary to IE after MitraClip can be successfully carried out
despite a high surgical risk.
PMID- 25136887
TI - Single bolus intravenous regadenoson injection versus central venous infusion of
adenosine for maximum coronary hyperaemia in fractional flow reserve measurement.
AB - AIMS: The aim of this study was to compare the hyperaemic effect of a single
bolus regadenoson injection to a central venous adenosine infusion for inducing
hyperaemia in the measurement of fractional flow reserve (FFR). METHODS AND
RESULTS: One hundred patients scheduled for FFR measurement were enrolled. FFR
was first measured by IV adenosine (140 ug/kg/min), thereafter by IV bolus
regadenoson injection (400 ug), followed by another measurement by IV adenosine
and bolus injection of regadenoson. The regadenoson injections were randomised to
central or peripheral intravenous. Hyperaemic response and duration of steady
state maximum hyperaemia were studied, central versus peripheral venous
regadenoson injections were compared, and safety and reproducibility of repeated
injections were investigated. Mean age was 66+/-8 years, 75% of the patients were
male. The target stenosis was located in the LM, LAD, LCX, and RCA in 7%, 54%,
20% and 19%, respectively. There was no difference in FFR measured by adenosine
or by regadenoson (DeltaFFR=0.00+/-0.01, r=0.994, p<0.001). Duration of maximum
hyperaemia after regadenoson was variable (10-600 s). No serious side effects of
either drug were observed. CONCLUSIONS: Maximum coronary hyperaemia can be
achieved easily, rapidly, and safely by one single intravenous bolus of
regadenoson administered either centrally or peripherally. Repeated regadenoson
injections are safe. The hyperaemic plateau is variable. Clinical Trial
Registration: http://clinicaltrials.gov/ct2/
show/study/NCT01809743?term=NCT01809743&rank=1 (ClinicalTrials.gov Identifier:
NCT01809743).
PMID- 25136888
TI - Safety of second-generation drug-eluting stents three years after randomised use
in the TWENTE trial.
AB - AIMS: To assess three-year clinical outcome following randomised use of the
second-generation Resolute zotarolimus-eluting stent (ZES) and the XIENCE V
everolimus-eluting stent (EES). For Resolute ZES and randomised use, outcome data
>=3 years are relatively scarce. METHODS AND RESULTS: The TWENTE trial examined
1,391 patients with stable angina or non-ST-elevation acute coronary syndromes,
of whom 21.6% were diabetics, 70.1% had complex B2 or C lesions and 77.4% had
"off-label" indications for DES use. Three-year follow-up data were obtained in
1,381 patients (99.3%; 10 withdrawals). Adverse clinical events were
independently adjudicated. The primary endpoint target vessel failure (TVF), a
composite of cardiac death, target vessel-related myocardial infarction and
clinically indicated target vessel revascularisation, was 12.1% for Resolute ZES
and 13.4% for XIENCE V EES (p=0.50). Cardiac death rates were 1.9% vs. 3.5%
(p=0.06); the other individual components of TVF also showed no significant
between-group differences. The rates of definite-or-probable stent thrombosis
(1.4% vs. 1.6%, p=0.82) and very late stent thrombosis (0.6% vs. 0.4%, p=1.0) did
not differ between the groups. CONCLUSIONS: Three-year follow-up data of patients
included in the randomised TWENTE trial demonstrated similar and sustained safety
and efficacy of Resolute ZES and XIENCE V EES.
PMID- 25136889
TI - Investigation of manic and euthymic episodes identifies state- and trait-specific
gene expression and STAB1 as a new candidate gene for bipolar disorder.
AB - Bipolar disorder (BD) is a highly heritable psychiatric disease characterized by
recurrent episodes of mania and depression. To identify new BD genes and
pathways, the present study employed a three-step approach. First, gene
expression profiles of BD patients were assessed during both a manic and an
euthymic phase. These profiles were compared intra-individually and with the gene
expression profiles of controls. Second, those differentially expressed genes
that were considered potential trait markers of BD were validated using data from
the Psychiatric Genomics Consortiums' genome-wide association study (GWAS) of BD.
Third, the implicated molecular mechanisms were investigated using pathway
analytical methods. In the present patients, this novel approach identified: (i)
sets of differentially expressed genes specific to mania and euthymia; and (ii) a
set of differentially expressed genes that were common to both mood states. In
the GWAS data integration analysis, one gene (STAB1) remained significant (P=1.9
* 10(-4)) after adjustment for multiple testing. STAB1 is located in close
proximity to PBMR1 and the NEK4-ITIH1-ITIH3-ITIH4 region, which are the top
findings from GWAS meta-analyses of mood disorder, and a combined BD and
schizophrenia data set. Pathway analyses in the mania versus control comparison
revealed three distinct clusters of pathways tagging molecular mechanisms
implicated in BD, for example, energy metabolism, inflammation and the ubiquitin
proteasome system. The present findings suggest that STAB1 is a new and highly
promising candidate gene in this region. The combining of gene expression and
GWAS data may provide valuable insights into the biological mechanisms of BD.
PMID- 25136893
TI - Viscoelasticity and interface bending properties of lecithin reverse wormlike
micelles studied by diffusive wave spectroscopy in hydrophobic environment.
AB - Upon the addition of minute quantities of water into a phosphatidylcholine (PC)
solution in certain organic solvents, PC micelles elongate into giant reverse
wormlike micelles that entangle and form highly viscous microemulsions, called
lecithin organogels. We investigated the microrheological properties of
concentrated PC-cyclohexane reverse wormlike micellar systems by diffusive wave
spectroscopy (DWS) in apolar medium, combined with bulk shear rheology. We
applied DWS to our oil-continuous system by using hydrophobic poly(hydroxystearic
acid)-grafted PMMA particles as monodisperse tracer particles. Relevant
parameters such as the micellar scission energy and persistence length were
extracted from the microrheology data and interpreted according to the sphere-to
rod-to-sphere structural transition. On the basis of these quantities, we
calculated the bending and saddle-splay moduli of the PC-covered water
cyclohexane interface. This approach represents a new method for the quantitative
estimation of these fundamental parameters, which are thought to underpin the
self-assembly of surfactants.
PMID- 25136892
TI - Lithospermum erythrorhizon extract protects keratinocytes and fibroblasts against
oxidative stress.
AB - Oxidative stress damages dermal and epidermal cells and degrades extracellular
matrix proteins, such as collagen, ultimately leading to skin aging. The present
study evaluated the potential protective effect of the aqueous methanolic extract
obtained from Lithospermum erythrorhizon (LE) against oxidative stress, induced
by H2O2 and ultraviolet (UV) irradiation, on human keratinocyte (HaCaT) and human
dermal fibroblast-neonatal (HDF-n) cells. Exposure of cells to H2O2 or UVB
irradiation markedly increased oxidative stress and reduced cell viability.
However, pretreatment of cells with the LE extract not only increased cell
viability (up to 84.5%), but also significantly decreased oxidative stress.
Further, the LE extract downregulated the expression of matrix metalloproteinase
1, an endopeptidase that degrades extracellular matrix collagen. In contrast,
treatment with the LE extract did not affect the expression of procollagen type 1
in HDF-n cells exposed to UVA irradiation. Thirteen phenolic compounds, including
derivatives of shikonin and caffeic acid, were identified by ultrahigh
performance liquid chromatography-electrospray ionization-tandem mass
spectrometry. These results suggest that LE-derived extracts may protect
oxidative-stress-induced skin aging by inhibiting degradation of skin collagen,
and that this protection may derive at least in part from the antioxidant
phenolics present in these extracts. Further studies are warranted to determine
the potential utility of LE-derived extracts in both therapeutic and cosmetic
applications.
PMID- 25136894
TI - Chromatic induction from surrounding stimuli under perceptual suppression.
AB - The appearance of colors can be affected by their spatiotemporal context. The
shift in color appearance according to the surrounding colors is called color
induction or chromatic induction; in particular, the shift in opponent color of
the surround is called chromatic contrast. To investigate whether chromatic
induction occurs even when the chromatic surround is imperceptible, we measured
chromatic induction during interocular suppression. A multicolor or uniform color
field was presented as the surround stimulus, and a colored continuous flash
suppression (CFS) stimulus was presented to the dominant eye of each subject. The
subjects were asked to report the appearance of the test field only when the
stationary surround stimulus is invisible by interocular suppression with CFS.
The resulting shifts in color appearance due to chromatic induction were
significant even under the conditions of interocular suppression for all surround
stimuli. The magnitude of chromatic induction differed with the surround
conditions, and this difference was preserved regardless of the viewing
conditions. The chromatic induction effect was reduced by CFS, in proportion to
the magnitude of chromatic induction under natural (i.e., no-CFS) viewing
conditions. According to an analysis with linear model fitting, we revealed the
presence of at least two kinds of subprocesses for chromatic induction that
reside at higher and lower levels than the site of interocular suppression. One
mechanism yields different degrees of chromatic induction based on the complexity
of the surround, which is unaffected by interocular suppression, while the other
mechanism changes its output with interocular suppression acting as a gain
control. Our results imply that the total chromatic induction effect is achieved
via a linear summation of outputs from mechanisms that reside at different levels
of visual processing.
PMID- 25136890
TI - Dysfunctional dopaminergic neurotransmission in asocial BTBR mice.
AB - Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized
by pronounced social and communication deficits and stereotyped behaviours.
Recent psychosocial and neuroimaging studies have highlighted reward-processing
deficits and reduced dopamine (DA) mesolimbic circuit reactivity in ASD patients.
However, the neurobiological and molecular determinants of these deficits remain
undetermined. Mouse models recapitulating ASD-like phenotypes could help generate
hypotheses about the origin and neurophysiological underpinnings of clinically
relevant traits. Here we used functional magnetic resonance imaging (fMRI),
behavioural and molecular readouts to probe dopamine neurotransmission
responsivity in BTBR T(+) Itpr3(tf)/J mice (BTBR), an inbred mouse line widely
used to model ASD-like symptoms owing to its robust social and communication
deficits, and high level of repetitive stereotyped behaviours. C57BL/6J (B6) mice
were used as normosocial reference comparators. DA reuptake inhibition with GBR
12909 produced significant striatal DA release in both strains, but failed to
elicit fMRI activation in widespread forebrain areas of BTBR mice, including
mesolimbic reward and striatal terminals. In addition, BTBR mice exhibited no
appreciable motor responses to GBR 12909. DA D1 receptor-dependent behavioural
and signalling responses were found to be unaltered in BTBR mice, whereas
dramatic reductions in pre- and postsynaptic DA D2 and adenosine A2A receptor
function was observed in these animals. Overall these results document profoundly
compromised DA D2-mediated neurotransmission in BTBR mice, a finding that is
likely to have a role in the distinctive social and behavioural deficits
exhibited by these mice. Our results call for a deeper investigation of the role
of dopaminergic dysfunction in mouse lines exhibiting ASD-like phenotypes, and
possibly in ASD patient populations.
PMID- 25136895
TI - The rise of China in the International Trade Network: a community core detection
approach.
AB - Theory of complex networks proved successful in the description of a variety of
complex systems ranging from biology to computer science and to economics and
finance. Here we use network models to describe the evolution of a particular
economic system, namely the International Trade Network (ITN). Previous studies
often assume that globalization and regionalization in international trade are
contradictory to each other. We re-examine the relationship between globalization
and regionalization by viewing the international trade system as an
interdependent complex network. We use the modularity optimization method to
detect communities and community cores in the ITN during the years 1995-2011. We
find rich dynamics over time both inter- and intra-communities. In particular,
the Asia-Oceania community disappeared and reemerged over time along with a
switch in leadership from Japan to China. We provide a multilevel description of
the evolution of the network where the global dynamics (i.e., communities
disappear or reemerge) and the regional dynamics (i.e., community core changes
between community members) are related. Moreover, simulation results show that
the global dynamics can be generated by a simple dynamic-edge-weight mechanism.
PMID- 25136896
TI - Is non-high-density lipoprotein cholesterol a marker and therapeutic target for
dyslipidemia in metabolic syndrome?
PMID- 25136897
TI - Real-world evidence in pain research: a review of data sources.
AB - Outcomes research studies use clinical and administrative data generated in the
course of patient care or from patient surveys to examine the effectiveness of
treatments. Health care providers need to understand the limitations and
strengths of the real-world data sources used in outcomes studies to meaningfully
use the results. This paper describes five types of databases commonly used in
the United States for outcomes research studies, discusses their strengths and
limitations, and provides examples of each within the context of pain treatment.
The databases specifically discussed are generated from (1) electronic medical
records, which are created from patient-provider interactions; (2) administrative
claims, which are generated from providers' and patients' transactions with
payers; (3) integrated health systems, which are generated by systems that
provide both clinical care and insurance benefits and typically represent a
combination of electronic medical record and claims data; (4) national surveys,
which provide patient-reported responses about their health and behaviors; and
(5) patient registries, which are developed to track patients with a given
disease or exposure over time for specified purposes, such as population
management, safety monitoring, or research.
PMID- 25136898
TI - An examination of global and regional opioid consumption trends 1980-2011.
AB - Despite expert recognition that strong opioid analgesics are the cornerstone of
treatment for moderate to severe pain, most of the world's population lacks
adequate availability of opioids. Moreover, great disparities in availability of
opioids continue to exist between higher- and lower-to-middle-income countries.
This study examined more than 30 years of consumption data reported to the
International Narcotics Control Board, from 1980 to 2011, for five opioids that
are indicated for the treatment of moderate to severe pain: fentanyl,
hydromorphone, morphine, oxycodone, and pethidine. As such, this study offers a
regional and global perspective on opioid consumption, providing an indication of
preparedness for treating moderate to severe pain. Countries are categorized
according to the World Health Organization's six geographical regions. Morphine
equivalence (ME) statistics were calculated for each study drug, allowing for
equianalgesic comparisons between consumption of the study opioids and well as
the ability to aggregate all study opioids (Total ME). The ME statistic is
adjusted for country population, which allows for uniform global-, regional-, and
country-level equianalgesic comparisons of consumption of morphine with other
opioids. Although overall trend lines revealed general increases by region,
profound inequities in opioid consumption continue to abound globally.
PMID- 25136899
TI - TRPS1 Haploinsufficiency Results in Increased STAT3 and SOX9 mRNA Expression in
Hair Follicles in Trichorhinophalangeal Syndrome.
PMID- 25136900
TI - Effect of cleansing methods on saliva-contaminated zirconia--an evaluation of
resin bond durability.
AB - The aims of this study were to investigate 1) the influence of cleansing methods
after saliva contamination and 2) aging conditions (thermocycling and water
storage) on zirconia shear bond strength (SBS) with a resin cement. One hundred
and eighty zirconia specimens were sandblasted with 50 MUm aluminum oxide
particles, immersed in saliva for one minute (with the exception of the control
group, [C]), and divided into groups according to the cleansing method, as
follows: water rinse (W); 37% phosphoric acid gel (PA); cleaning paste (ie,
Ivoclean(r)) containing mainly zirconium oxide (IC); and 70% isopropanol (AL).
Scanning electron microscopy was done to qualitatively evaluate the zirconia
surface after each cleansing method. For the SBS test, resin cement buttons were
bonded to the specimens using a dedicated jig. SBS was evaluated according to
standard protocols after 24 hours, 5000 thermal cycles (TC), or 150 days of water
storage. Statistical analysis was performed using two-way analysis of variance
and Tukey test (p<0.05). Data showed a significant effect for the 150 days of
water storage, TC, and 24 hours of water storage (150 days < TC < 24 hours).
Group comparisons showed that PA < AL and W < IC and C. SBS ranged from 10.4 to
21.9 MPa (24 hours), from 6.4 to 14.8 MPa (TC), and from 2.9 to 7.0 MPa (150
days). Failure analysis revealed a greater percentage of mixed failures for the
majority of the specimens and a smaller percentage of adhesive failures at the
ceramic-resin cement interface. Our findings suggest that Ivoclean(r) was able to
maintain adequate SBS values after TC and 150 days of storage, comparable to the
uncontaminated zirconia.
PMID- 25136901
TI - Transdentinal cell photobiomodulation using different wavelengths.
AB - OBJECTIVE: The aim of this study was to investigate the effects of transdentinal
irradiation with different light-emitting diode (LED) parameters on odontoblast
like cells (MDPC-23). METHODS AND MATERIALS: Human dentin discs (0.2 mm thick)
were obtained, and cells were seeded on their pulp surfaces with complete culture
medium (Dulbecco modified Eagle medium). Discs were irradiated from the occlusal
surfaces with LED at different wavelengths (450, 630, and 840 nm) and energy
densities (0, 4, and 25 J/cm(2)). Cell viability (methyltetrazolium assay),
alkaline phosphatase activity (ALP), total protein synthesis (TP), and cell
morphology (scanning electron microscopy) were evaluated. Gene expression of
collagen type I (Col-I) was analyzed by quantitative polymerase chain reaction
(PCR). Data were analyzed by the Mann-Whitney test with a 5% significance level.
RESULTS: Higher cell viability (21.8%) occurred when the cells were irradiated
with 630 nm LED at 25 J/cm(2). Concerning TP, no statistically significant
difference was observed between irradiated and control groups. A significant
increase in ALP activity was observed for all tested LED parameters, except for
450 nm at 4 J/cm(2). Quantitative PCR showed a higher expression of Col-I by the
cells subjected to infrared LED irradiation at 4 J/cm(2). More attached cells
were observed on dentin discs subjected to irradiation at 25 J/cm(2) than at 4
J/cm(2). CONCLUSION: The infrared LED irradiation at an energy density of 4
J/cm(2) and red LED at an energy density of 25 J/cm(2) were the most effective
parameters for transdentinal photobiomodulation of cultured odontoblast-like
cells.
PMID- 25136902
TI - Effect of hydrogen peroxide concentration on enamel color and microhardness.
AB - OBJECTIVES: The aim of this study was to investigate the effect of hydrogen
peroxide gels with different concentrations (20%, 25%, 30%, and 35%) on enamel
Knoop microhardness (KNH) as well as on changes in dental color (C). METHODS:
Cylindrical specimens of enamel/dentin (3-mm diameter and 2-mm thickness) were
obtained from bovine incisors and randomly divided into six groups (n=20),
according to the concentration of the whitening gel (20%, 25%, 30%, 35%, control,
thickener). After polishing, initial values of KNH0 and color measurement,
assessed by spectrophotometry using the CIE L*a*b* system, were taken from the
enamel surface. The gels were applied on the enamel surface for 30 minutes, and
immediate values of KNHi were taken. After seven days of being stored in
artificial saliva, new measures of KNH7 and color (L7* a7* b7*, for calculating
DeltaE, DeltaL, and Deltab) were made. Data were submitted to statistical
analysis of variance, followed by Tukey test (p<0.05). RESULTS: Differences in
gel concentration and time did not influence the microhardness (p=0.54 and
p=0.29, respectively). In relation to color changes, DeltaE data showed that the
35% gel presented a higher color alteration than the 20% gel did (p=0.006).
CONCLUSION: Bleaching with 35% hydrogen peroxide gel was more effective than with
the 20% gel, without promoting significant adverse effects on enamel surface
microhardness.
PMID- 25136903
TI - Influence of pH on the effectiveness of hydrogen peroxide whitening.
AB - OBJECTIVE: To evaluate the influence of pH on the bleaching effect of hydrogen
peroxide on chromogen agents. METHOD: Hydrogen peroxide 50% was mixed with red
wine or with an alcoholic solution of tobacco in glass cuvettes, resulting in
final peroxide concentrations of 16.97% and 21.12%, respectively. The pH of this
mixture was measured and adjusted with 3.3 M HCl solution or 2.5 M NaOH solution
to obtain the final pH values of 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, and 9.0. After
mixing, the color of these solutions was evaluated in a reflectance
spectrophotometer; readings were repeated after 10 minutes for the wine solution
and 20 minutes for the tobacco solution. Ten samples were prepared for each
solution at each pH. Color changes (Delta E) were calculated. The data were
statistically analyzed using analysis of variance one-way and Tukey tests, with a
significance level of 5%. RESULTS: There were significant differences among the
different pH values for the wine and tobacco solutions (p=0.0001). The Tukey test
showed that for both solutions, pH 9.0 resulted in a significantly greater
bleaching effect than the other values tested. CONCLUSION: The efficacy of
hydrogen peroxide bleaching is directly proportional to the increase in its pH.
PMID- 25136904
TI - Polymerization shrinkage and depth of cure of bulk-fill resin composites and
highly filled flowable resin.
AB - The aim of this study was to evaluate the polymerization behavior and depth of
cure (DOC) of recently introduced resin composites for posterior use: highly
filled flowable composite and composites for bulk fill. A highly filled flowable
(G-aenial Universal Flo [GUF]), two bulk-fill flowables (Surefil SDR Flow [SDR]
and Venus Bulk fill [VBF]), and a bulk-fill nonflowable composite (Tetric N-Ceram
Bulk fill [TBF]) were compared with two conventional composites (Tetric Flow
[TF], Filtek Supreme Ultra [FS]). Linear polymerization shrinkage and
polymerization shrinkage stress were each measured with custom-made devices. To
evaluate DOC, the composite specimen was prepared using a mold with a hole of 4
mm depth and 4 mm internal diameter. The hole was bulk filled with each of the
six composites and light cured for 20 seconds, followed by 24 hours of water
storage. The surface hardness was measured on the top and the bottom using a
Vickers microhardness (HV) indenter. The linear polymerization shrinkage of the
composite specimens after photo-initiation decreased in the following order: TF
and GUF > VBF > SDR > FS and TBF (p<0.05). The polymerization shrinkage stress of
the six composite groups decreased in the following order: GUF > TF and VBF > SDR
> FS and TBF (p<0.05). The mean bottom surface HV of SDR and VBF exceeded 80% of
the top surface HV (HV-80%). However, the bottom of GUF and TBF failed to reach
HV-80%. A highly filled flowable (GUF) revealed limitations in polymerization
shrinkage and DOC. Bulk-fill flowables (SDR and VBF) were properly cured in 4-mm
bulk, but they shrank more than the conventional nonflowable composite. A bulk
fill nonflowable (TBF) showed comparable shrinkage to the conventional
nonflowable composite, but it was not sufficiently cured in the 4-mm bulk.
PMID- 25136905
TI - Color masking of developmental enamel defects: a case series.
AB - Developmental defects involving color alteration of enamel frequently compromise
the esthetic appearance of the tooth. The resin infiltration technique represents
an alternative treatment for color masking of these lesions and uniformization of
tooth color. This technique is considered relatively simple and microinvasive,
since only a minimal portion of enamel is removed. This article illustrates the
color-masking effect with resin infiltration of fluorosis and traumatic
hypomineralization lesions with a case series. The final esthetic outcomes
demonstrated the ability of the resin infiltrant to mask the color of white
developmental defect lesions, resulting in satisfactory clinical esthetic
improvements. However, in more severe cases, the color-masking effect was not
complete.
PMID- 25136906
TI - Efficiency of dual-cured resin cement polymerization induced by high-intensity
LED curing units through ceramic material.
AB - OBJECTIVE: This study aimed to evaluate the ability of high-intensity light
emitting diode (LED) and other curing units to cure dual-cured resin cement
through ceramic material. METHODS: A halogen curing unit (Jetlite 3000, Morita),
a second-generation LED curing unit (Demi, Kerr), and two high-intensity LED
curing units (PenCure 2000, Morita; Valo, Ultradent) were tested. Feldspathic
ceramic plates (VITABLOCS Mark II, A3; Vita Zahnfabrik) with thicknesses of 1.0,
2.0, and 3.0 mm were prepared. Dual-cured resin cement samples (Clearfil Esthetic
Cement, Kuraray Noritake Dental) were irradiated directly or through one of the
ceramic plates for different periods (5, 10, 15, or 20 seconds for the high
intensity LED units and 20, 40, 60, or 80 seconds for the others). The Knoop
hardness test was used to determine the level of photopolymerization that had
been induced in the resin cement. Data were analyzed by one-way analysis of
variance and Dunnett's post-hoc test to identify test-control (maximum
irradiation without a ceramic plate) differences for each curing unit (p<0.05).
RESULTS: For all curing units, the curing conditions had a statistically
significant effect on the Knoop hardness numbers (KHNs) of the irradiated cement
samples (p<0.001). In general, the KHN decreased with increasing plate thickness
and increased as the irradiation period was extended. Jetlite 3000 achieved
control-level KHN values only when the plate thickness was 1.0 mm. At a plate
thickness >=2.0 mm, the LED units (except for PenCure 2000 at 3.0 mm) were able
to achieve control-level KHN values when the irradiation time was extended. At a
plate thickness of 3.0 mm, irradiation for 20 seconds with the Valo or for 80
seconds with the Demi were the only methods that produced KHN values equivalent
to those produced by direct irradiation. CONCLUSION: Regardless of the type of
curing unit used, indirect irradiation of dual-cured resin cement through a
ceramic plate resulted in decreased KHN values compared with direct irradiation.
When the irradiation period was extended, only the LED units were able to achieve
similar KHN values to those observed under direct irradiation in the presence of
plates >=2.0-mm thick. High-intensity LED units require a shorter irradiation
period than halogen and second-generation LED curing units to obtain KHN values
similar to those observed during direct irradiation.
PMID- 25136907
TI - A case report of gingival enlargement associated with invasive cervical
resorption.
AB - Invasive cervical resorption (ICR) is a rare external dental resorption with
unknown etiology; it progresses asymptomatically in the cervical area of the
permanent teeth. Lesions are mostly misdiagnosed as internal resorption or
caries, which leads to erroneous treatments. This case report presents the
clinical and radiological diagnosis, as well as the results of treatment and 3
year follow-up in a 50-year-old female patient with gingival enlargement
associated with ICR in tooth No. 25. Granulation tissue was removed by accessing
the cervical resorption area through a flap operation. Following the endodontic
treatment, the tooth was restored using composite resin and the hyperplastic
lesion was excised. In conclusion, it should be kept in mind that clinical,
radiological, and pathological evaluation in the differential diagnosis of
localized hyperplastic lesions in the gingiva is of importance and that ICR could
play a role in the etiology of these lesions.
PMID- 25136909
TI - The chemistry of imperfections in N-graphene.
AB - Many propositions have been already put forth for the practical use of N-graphene
in various devices, such as batteries, sensors, ultracapacitors, and next
generation electronics. However, the chemistry of nitrogen imperfections in this
material still remains an enigma. Here we demonstrate a method to handle N
impurities in graphene, which allows efficient conversion of pyridinic N to
graphitic N and therefore precise tuning of the charge carrier concentration. By
applying photoemission spectroscopy and density functional calculations, we show
that the electron doping effect of graphitic N is strongly suppressed by
pyridinic N. As the latter is converted into the graphitic configuration, the
efficiency of doping rises up to half of electron charge per N atom.
PMID- 25136911
TI - Cycloartane triterpenoids and their glycosides from the rhizomes of Cimicifuga
foetida.
AB - A phytochemical study on the rhizomes of Cimicifuga foetida resulted in the
isolation of two new cycloartane triterpenoids (1 and 2), eight new cycloartane
glycosides (3-10), and six known cycloartane glycoside analogues (11-16). The
structures of 1-10 were determined by application of spectroscopic methods, with
the absolute configuration of 1 determined by X-ray crystallography. Compounds 1
6, as three pairs of epimers at C-10 and C-24, belong to a seven-membered-ring
variant of 9,10-seco-9,19-cycloartane triterpenoids, and glycosides 3-10 were
found to be 3-O-beta-D-xylopyranosides. The cytotoxicity of the isolates was
evaluated against five selected human tumor cell lines, and the known compounds
15 and 16 showed cytotoxicity against the hepatocellular carcinoma SMMC-7721 cell
line with IC50 values of 5.5 and 6.3 MUM, respectively.
PMID- 25136908
TI - A novel microRNA-132-sirtuin-1 axis underlies aberrant B-cell cytokine regulation
in patients with relapsing-remitting multiple sclerosis [corrected].
AB - Clinical trial results demonstrating that B-cell depletion substantially reduces
new relapses in patients with multiple sclerosis (MS) have established that B
cells play a role in the pathophysiology of MS relapses. The same treatment
appears not to impact antibodies directed against the central nervous system,
which underscores the contribution of antibody-independent functions of B cells
to disease activity. One mechanism by which B cells are now thought to contribute
to MS activity is by over-activating T cells, including through aberrant
expression of B cell pro-inflammatory cytokines. However, the mechanisms
underlying the observed B cell cytokine dysregulation in MS remain unknown. We
hypothesized that aberrant expression of particular microRNAs might be involved
in the dysregulated pro-inflammatory cytokine responses of B cells of patients
with MS. Through screening candidate microRNAs in activated B cells of MS
patients and matched healthy subjects, we discovered that abnormally increased
secretion of lymphotoxin and tumor necrosis factor alpha by MS B cells is
associated with abnormally increased expression of miR-132. Over-expression of
miR-132 in normal B cells significantly enhanced their production of lymphotoxin
and tumor necrosis factor alpha. The over-expression of miR-132 also suppressed
the miR-132 target, sirtuin-1. We confirmed that pharmacological inhibition of
sirtuin-1 in normal B cells induces exaggerated lymphotoxin and tumor necrosis
factor alpha production, while the abnormal production of these cytokines by MS B
cells can be normalized by resveratrol, a sirtuin-1 activator. These results
define a novel miR-132-sirtuin-1 axis that controls pro-inflammatory cytokine
secretion by human B cells, and demonstrate that a dysregulation of this axis
underlies abnormal pro-inflammatory B cell cytokine responses in patients with
MS.
PMID- 25136912
TI - My career path for developing gene therapy for blinding diseases: the importance
of mentors, collaborators, and opportunities.
PMID- 25136914
TI - Gene therapy briefs.
PMID- 25136915
TI - Emerging neuronal precursors from amniotic fluid-derived down syndrome induced
pluripotent stem cells.
PMID- 25136917
TI - Medication overuse headache - An under-diagnosed problem in shunted idiopathic
intracranial hypertension patients.
AB - Purpose. Management of headache in a subgroup of shunted idiopathic intracranial
hypertension (IIH) patients is a well- described and difficult task. We present
our series of shunted IIH patients with medication overuse headache (MOH) and
discuss the role of careful pain management in this group of patients. Materials
and methods. A retrospective review of shunted IIH patients with headache, who
had their shunt function assessed by monitoring their intracranial pressure and
were subsequently diagnosed with MOH. Results. A total of 15 patients were
identified. The mean time between the diagnosis of IIH and the diagnosis of
medication overuse headache was 6 years (standard deviation 4.9, range 2-18
years). The majority of patients in this group (12/15) had undergone multiple
shunt revisions. Conclusions. Medication overuse headache in shunted IIH patients
can lead to the requirement of hospital admission, investigations and procedures.
We suggest that opiates and non-steroidal anti-inflammatory analgesics (NSAIDs)
are used for a specified duration post-operatively and reviewed regularly. We
suggest that patients are counselled regarding medication overuse headache in a
multidisciplinary setting.
PMID- 25136913
TI - Retinal gene therapy using adeno-associated viral vectors: multiple applications
for a small virus.
PMID- 25136918
TI - Surface plasmon dependence on the electron density profile at metal surfaces.
AB - We use an extension of the hydrodynamic model to study nonlocal effects in the
collective plasmon excitations at metal surfaces and narrow gaps between metals,
including the surface spill-out of conduction band electrons. In particular, we
simulate metal surfaces consisting of a smooth conduction-electron density
profile and an abrupt jellium edge. We focus on aluminum and gold as prototypical
examples of simple and noble metals, respectively. Our calculations agree with
the dispersion relations measured from planar surfaces for these materials.
Systems involving small gaps display a regime of tunnelling electrons, which is
partially captured by the overlap of electron densities. This extension of the
hydrodynamic model to cope with inhomogeneous density profiles provides a
relatively fast and accurate way of describing the optical response of metal
surfaces at subnanometer distances.
PMID- 25136919
TI - Have preferences of girls changed almost 3 years after the much debated start of
the HPV vaccination program in The Netherlands? A discrete choice experiment.
AB - OBJECTIVES: To assess how girls' preferences have changed almost 3 years after
the much debated start of the human papillomavirus (HPV) vaccination program.
METHODS: A discrete choice experiment (DCE) was conducted among girls aged 11-15
years who were invited, or were not yet invited, to get vaccinated. A panel
latent class model was used to determine girls' preferences for vaccination based
on five characteristics: degree of protection against cervical cancer; duration
of protection; risk of mild side-effects; age of vaccination; and the number of
required doses of the vaccine. RESULTS: The response rate was 85% (500/592). Most
girls preferred vaccination at age 14 years (instead of at age 9 years) and a 2
dose scheme (instead of the current 3-dose scheme). Girls were willing to trade
off 7% (CI: 3.2% to 10.8%) of the degree of protection to have 10% less risk of
mild side-effects, and 4% (CI: 1.2% to 5.9%) to receive 2 doses instead of 3
doses. Latent class analyses showed that there was preference heterogeneity among
girls, i.e., higher educated girls and HPV vaccinated girls had a higher
probability to opt for HPV vaccination at a higher age than lower educated girls
or non-vaccinated girls. CONCLUSIONS: Three years after the start of HPV
vaccination program the risk of mild side-effects and age at vaccination seem to
have become less important. For the Dutch national immunization program, we
recommend not to lower the current target age of 12 years. A 2-dose scheme may
result in a higher uptake and we recommend that if this scheme is introduced, it
needs to receive adequate publicity.
PMID- 25136920
TI - Analysis of lymph node metastasis correlation with prognosis in patients with T2
gastric cancer.
AB - PURPOSE: To investigate the correlated factors for lymph node metastasis and
prognosis for patients with T2 gastric cancer. METHODS: A total of 442 patients
with T2 gastric cancer who underwent gastrectomy from January 1996 to December
2009 were evaluated. The clinicopathological parameters were analyzed for lymph
node metastasis and prognosis, including gender, age, tumor size, tumor location,
histological type, depth of invasion, vascular tumor emboli, nervous invasion,
resection type, and pathological stage. RESULTS: The rate of lymph node
metastasis was 45.9%. Univariate analysis showed that depth of invasion, tumor
size, and vascular tumor emboli were associated with lymph node metastasis.
Logistic regression demonstrated that depth of invasion, tumor size, and vascular
tumor emboli were independently predictive factors for lymph node metastasis. The
5-year survival rate was 64.0%. Multivariate analysis showed that tumor size,
tumor location, resection type, and pathological stage were independent
prognostic factors. Based on tumor size, there were significant differences of 5
year survival between small size tumor (<6 cm) and large size tumor (>= 6 cm)
according to stage IIA (P = 0.006). Based on tumor location, there were
significant differences of 5-year survival among different tumor location
according to stage IB. Based on resection type, there were significant
differences of overall 5-year survival between curative surgery and palliative
surgery according to stage IIB (P = 0.015) and IIIA (P = 0.001). CONCLUSION:
Depth of invasion, tumor size, and vascular tumor emboli were independently
predictive factors for lymph node metastasis. Tumor size, tumor location,
resection type, and pathological stage were independent prognostic factors.
PMID- 25136923
TI - New technique of immediate nipple reconstruction during immediate autologous DIEP
or MS-TRAM breast reconstruction.
AB - BACKGROUND: Reconstruction of the nipple-areola complex is the final step in
surgical restoration of the breast. Usually considered a secondary complement to
breast reconstruction, nipple-areola creation is ordinarily done after an
interval of several months using different techniques involving local flaps or
composite graft from the opposite nipple. METHODS: Because the position of the
nipple-areola complex is well defined from the outset in skin-sparing mastectomy,
the authors propose a new technique of immediate nipple reconstruction using the
skin envelope after skin-sparing mastectomy. A modified wise pattern design of
skin-sparing mastectomy with 3 local flaps is used. The dermal-fat flaps are
lifted and sutured together to form the new nipple. RESULTS: Seventeen patients
(average age, 47 years; range, 33-58 years) underwent immediate nipple
reconstruction between March 2010 and January 2012 (11 bilateral and 6 unilateral
cases). Average follow-up was 13 months (range, 2-25 months). Aesthetic results
were evaluated retrospectively from photographic documentation. A minimum average
score of 7.2 points was achieved in all evaluated criteria using a 10-point
scale. Patient satisfaction with nipple reconstruction was studied by means of a
questionnaire. The shape of the nipple received an average of 9.7 points and the
position of the nipple 9.9 points on the 10-point scale; 77% of patients were
also very satisfied with nipple sensitivity. CONCLUSIONS: One-stage nipple
reconstruction with immediate breast reconstruction using our technique of 3
local flaps on skin envelope flap is possible. This simple, reliable, and rapid
technique gives stable aesthetic results over time. Reconstruction may be
completed sooner and with fewer procedures. Nipple reconstruction should no
longer be considered as a secondary complement to immediate breast reconstruction
using deep inferior epigastric perforator or muscle-sparing transverse rectus
abdominis myocutaneous flap. Our technique is suitable for patients with ptotic
or hypertrophic breasts.
PMID- 25136922
TI - An E2F1-HOXB9 transcriptional circuit is associated with breast cancer
progression.
AB - Homeobox B9 (HOXB9), a member of the homeobox gene family, is overexpressed in
breast cancer and promotes tumor progression and metastasis by stimulating
epithelial-to-mesenchymal transition and angiogenesis within the tumor
microenvironment. HOXB9 activates the TGFbeta-ATM axis, leading to checkpoint
activation and DNA repair, which engenders radioresistance in breast cancer
cells. Despite detailed reports of the role of HOXB9 in breast cancer, the
factors that regulate HOXB9 transcription have not been extensively examined.
Here we uncover an underlying mechanism that may suggest novel targeting
strategies for breast cancer treatment. To identify a transcription factor
binding site (TFBS) in the HOXB9 promoter region, a dual luciferase reporter
assay was conducted. Protein candidates that may directly attach to a TFBS of
HOXB9 were examined by Q-PCR, electrophoretic mobility shift assay (EMSA),
chromatin immunoprecipitation (ChIP), and mutation analysis. A HOXB9 promoter
region from -404 to -392 was identified as TFBS, and E2F1 was a potential binding
candidate in this region. The induction of HOXB9 expression by E2F1 was observed
by Q-PCR in several breast cancer cell lines overexpressing E2F1. The stimulatory
effect of E2F1 on HOXB9 transcription and its ability to bind the TFBS were
confirmed by luciferase, EMSA and ChIP assay. Immunohistochemical analysis of 139
breast cancer tissue samples revealed a significant correlation between E2F1 and
HOXB9 expression (p<0.001). Furthermore, a CDK4/6 inhibitor suppressed E2F1
expression and also reduced expression of HOXB9 and its downstream target genes.
Our in vitro analysis identified the TFBS of the HOXB9 promoter region and
suggested that E2F1 is a direct regulator of HOXB9 expression; these data support
the strong correlation we found between E2F1 and HOXB9 in clinical breast cancer
samples. These results suggest that targeting the E2F1/HOXB9 axis may be a novel
strategy for the control or prevention of cancer progression and metastasis.
PMID- 25136924
TI - Nickel-based thin film on multiwalled carbon nanotubes as an efficient
bifunctional electrocatalyst for water splitting.
AB - Herein, we report electrodeposited nickel-based thin film (NiOx) on multiwalled
carbon nanotubes (MWCNTs) as a highly efficient bifunctional catalyst for both
the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Under
reductive conditions (-1.2 V vs Ag/AgCl), the hydrogen evolution catalyst (H2
NiO(x)) was facilely deposited on MWCNTs. The resulting film demonstrates good
catalytic activity for hydrogen production in a near-neutral aqueous solution at
low overpotential. When switched to oxidative conditions (+1.1 V vs Ag/AgCl), the
amorphous H2-NiO(x) film onto MWCNTs can be transformed into another amorphous
material (O2-NiO(x)) to efficiently catalyze OER. The NiO(x)-MWCNTs catalyst was
further characterized by scanning electron microscopy (SEM), energy-dispersive X
ray analysis (EDX), and X-ray photoelectron spectroscopy (XPS). The results show
that the content of oxygen in the O2-NiO(x)-MWCNTs film is higher than that in
the H2-NiO(x)-MWCNTs film. The NiOx-MWCNTs catalyst has good catalytic stability,
and the film is reversible when the potentials are switched between the reductive
conditions and oxidative conditions. The Faradaic efficiencies of hydrogen and
oxygen production are >95%.
PMID- 25136925
TI - Metamorphosis alters contaminants and chemical tracers in insects: implications
for food webs.
AB - Insects are integral to most freshwater and terrestrial food webs, but due to
their accumulation of environmental pollutants they are also contaminant vectors
that threaten reproduction, development, and survival of consumers. Metamorphosis
from larvae to adult can cause large chemical changes in insects, altering
contaminant concentrations and fractionation of chemical tracers used to
establish contaminant biomagnification in food webs, but no framework exists for
predicting and managing these effects. We analyzed data from 39 studies of 68
analytes (stable isotopes and contaminants), and found that metamorphosis effects
varied greatly. delta(15)N, widely used to estimate relative trophic position in
biomagnification studies, was enriched by ~ 10/00 during metamorphosis, while
delta(13)C used to estimate diet, was similar in larvae and adults. Metals and
polycyclic aromatic hydrocarbons (PAHs) were predominantly lost during
metamorphosis leading to ~ 2 to 125-fold higher larval concentrations and higher
exposure risks for predators of larvae compared to predators of adults. In
contrast, manufactured organic contaminants (such as polychlorinated biphenyls)
were retained and concentrated in adults, causing up to ~ 3-fold higher adult
concentrations and higher exposure risks to predators of adult insects. Both food
web studies and contaminant management and mitigation strategies need to consider
how metamorphosis affects the movement of materials between habitats and
ecosystems, with special regard for aquatic-terrestrial linkages.
PMID- 25136926
TI - Nitrite and hydroxylamine as nitrogenase substrates: mechanistic implications for
the pathway of N2 reduction.
AB - Investigations of reduction of nitrite (NO2(-)) to ammonia (NH3) by nitrogenase
indicate a limiting stoichiometry, NO2(-) + 6e(-) + 12ATP + 7H(+) -> NH3 + 2H2O +
12ADP + 12Pi. Two intermediates freeze-trapped during NO2(-) turnover by
nitrogenase variants and investigated by Q-band ENDOR/ESEEM are identical to
states, denoted H and I, formed on the pathway of N2 reduction. The proposed NO2(
) reduction intermediate hydroxylamine (NH2OH) is a nitrogenase substrate for
which the H and I reduction intermediates also can be trapped. Viewing N2 and
NO2(-) reductions in light of their common reduction intermediates and of NO2(-)
reduction by multiheme cytochrome c nitrite reductase (ccNIR) leads us to propose
that NO2(-) reduction by nitrogenase begins with the generation of NO2H bound to
a state in which the active-site FeMo-co (M) has accumulated two [e(-)/H(+)]
(E2), stored as a (bridging) hydride and proton. Proton transfer to NO2H and H2O
loss leaves M-[NO(+)]; transfer of the E2 hydride to the [NO(+)] directly to form
HNO bound to FeMo-co is one of two alternative means for avoiding formation of a
terminal M-[NO] thermodynamic "sink". The N2 and NO2(-) reduction pathways
converge upon reduction of NH2NH2 and NH2OH bound states to form state H with [
NH2] bound to M. Final reduction converts H to I, with NH3 bound to M. The
results presented here, combined with the parallels with ccNIR, support a N2
fixation mechanism in which liberation of the first NH3 occurs upon delivery of
five [e(-)/H(+)] to N2, but a total of seven [e(-)/H(+)] to FeMo-co when obligate
H2 evolution is considered, and not earlier in the reduction process.
PMID- 25136927
TI - Serum sphingolipids reflect the severity of chronic HBV infection and predict the
mortality of HBV-acute-on-chronic liver failure.
AB - Patients with HBV-acute-on-chronic liver failure (HBV-ACLF) have high mortality
and frequently require liver transplantation; few reliable prognostic markers are
available. As a class of functional lipids, sphingolipids are extensively
involved in the process of HBV infection. However, their role in chronic HBV
infection remains unknown. The aim of this study was to determine the serum
sphingolipid profile in a population of patients with chronic HBV infection,
paying special attention to exploring novel prognostic markers in HBV-ACLF. High
performance liquid chromatography tandem mass spectrometry was used to examine
the levels of 41 sphingolipids in 156 serum samples prospectively collected from
two independent cohorts. The training and validation cohorts comprised 20 and 28
healthy controls (CTRL), 29 and 23 patients with chronic hepatitis B (CHB), and
30 and 26 patients with HBV-ACLF, respectively. Biometric analysis was used to
evaluate the association between sphingolipid levels and disease stages.
Multivariate analysis revealed difference of sphingolipid profiles between CHB
and HBV-ACLF was more drastic than that between CTRL and CHB, which indicated
that serum sphingolipid levels were more likely to associate with the progression
HBV-ACLF rather than CHB. Furthermore, a 3-month mortality evaluation of HBV-ACLF
patients showed that dhCer(d18 : 0/24 : 0) was significantly higher in survivors
than in non-survivors (including deceased patients and those undergoing liver
transplantation, p < 0.05), and showed a prognostic performance similar to that
of the MELD score. The serum sphingolipid composition varies between CTRL and
chronic HBV infection patients. In addition, dhCer(d18 : 0/24 : 0) may be a
useful prognostic indicator for the early prediction of HBV-ACLF.
PMID- 25136928
TI - Synthesis and biological evaluation of kendomycin and its analogues.
AB - Ansa compounds are gifts from microbes with intriguing molecular structures and
highly potent bioactivities. One of the ansa compounds, kendomycin, has an oxa
metacyclophane skeleton with a quinone methide core and a fully substituted
tetrahydropyran ring. Beyond a common synthetic strategy for construction of the
ansa skeleton (i.e., elongation of an alkyl chain from an aromatic core followed
by macrocyclization), we challenged a new method for construction of the ansa
skeleton via simultaneous macrocyclization and benzannulation (using an
intramolecular Dotz benzannulation). Understanding the reactivity of various
Fischer-type omega-alkynyloxy chromium carbene complexes with kendomycin analogue
syntheses led to achievement of the total synthesis of kendomycin. Investigations
of structure-activity relationships revealed the need for an ansa skeleton for
antimicrobial activity. Therefore, we envisage that this intramolecular Dotz
benzannulation will enable divergent syntheses of ansa compounds which have
important bioactive potential.
PMID- 25136930
TI - Fibroepithelial polyp of the epiglottis.
AB - PATIENT: Male, 11. FINAL DIAGNOSIS: Fibroepithelial polyp of epiglottis.
SYMPTOMS: Dysphagia * sore throat. MEDICATION: -. CLINICAL PROCEDURE: -.
SPECIALTY: -. OBJECTIVE: Rare disease. BACKGROUND: Fibroepithelial polyp, a
common type of tumor in the skin and genitourinary tract, is very rare in the
respiratory tract. We describe clinical, radiologic, and histological features of
a fibroepithelial polyp as a rare cause of an epiglottic mass in a child. CASE
REPORT: An 11-year-old female presented with a 2-month history of sore throat and
dysphagia. Flexible laryngoscopy and MRI (magnetic resonance imaging) revealed a
mass on the lingual surface of the epiglottis. The mass was removed using a
carbon dioxide laser and was confirmed histologically as a fibroepithelial polyp.
CONCLUSIONS: Fibroepithelial polyp, although uncommon, should be considered in
the differential diagnosis of epiglottic mass in children.
PMID- 25136929
TI - Accounting for photophysical processes and specific signal intensity changes in
fluorescence-detected sedimentation velocity.
AB - Fluorescence detected sedimentation velocity (FDS-SV) has emerged as a powerful
technique for the study of high-affinity protein interactions, with hydrodynamic
resolution exceeding that of diffusion-based techniques, and with sufficient
sensitivity for binding studies at low picomolar concentrations. For the detailed
quantitative analysis of the observed sedimentation boundaries, it is necessary
to adjust the conventional sedimentation models to the FDS data structure. A key
consideration is the change in the macromolecular fluorescence intensity during
the course of the experiment, caused by slow drifts of the excitation laser
power, and/or by photophysical processes. In the present work, we demonstrate
that FDS-SV data have inherently a reference for the time-dependent
macromolecular signal intensity, resting on a geometric link between radial
boundary migration and plateau signal. We show how this new time-domain can be
exploited to study molecules exhibiting photobleaching and photoactivation. This
expands the application of FDS-SV to proteins tagged with photoswitchable
fluorescent proteins, organic dyes, or nanoparticles, such as those recently
introduced for subdiffraction microscopy and enables FDS-SV studies of their
interactions and size distributions. At the same time, we find that conventional
fluorophores undergo minimal photobleaching under standard illumination in the
FDS. These findings support the application of a high laser power density for the
detection, which we demonstrate can further increase the signal quality.
PMID- 25136931
TI - Comparison of the density of proteins and peptides grafted on silane layers and
polyelectrolyte multilayers.
AB - Immobilized proteins or peptides are of critical importance for applications such
as biosensing or cell culture. We analyze the structure of layers of a large
variety of proteins and peptides, grafted on silicon substrates by different
routes differing in the nature of the intermediate layer linking the biomolecules
to the substrate, either a silane monolayer, or a polyelectrolyte multilayer made
from synthetic or natural polymers. The structural analysis is essentially
performed by X-ray reflectometry, which proves to be an efficient methodology not
requiring the use of tagged biomolecules, capable of evaluating consistently the
amount of grafted biomolecules per surface area with estimated precisions ranging
from 10 to 20%. The study provides a quantitative basis for selecting one among a
series of well-proofed and sturdy grafting methodologies and underlines the
potential of XRR for assessing the amount of grafted biomacromolecules without
requiring the expensive tagging of molecules. Our results also show that, for the
coupling route resting on synthetic polyelectrolytes, the grafting density is
significantly lower than for direct coupling over a silane layer. In contrast,
when performed over a cushion based on polysaccharides, the grafting density is
well above the values found for a dense layer grafted on a silane monolayer,
indicating partial penetration and swelling of the polysaccharide cushion.
PMID- 25136932
TI - 1,3-Halogen migration as an entry to aryl coppers from an unintuitive starting
material.
AB - A copper(I) catalyzed 1,3-halogen migration/borylation migrates a bromine from an
sp(2) carbon to a benzylic carbon with concomitant borylation of the aryl-bromine
bond. This transformation proceeds via an aryl copper intermediate which can be
accessed independently and then trapped with electrophiles. As such, copper
catalyzed 1,3-halogen migration provides unique and mild access to an aryl copper
species that allows for rapid aromatic functionalization from an unconventional
starting material.
PMID- 25136933
TI - Combined antiretroviral therapy attenuates hepatic extracellular matrix
remodeling in HIV patients assessed by novel protein fingerprint markers.
AB - OBJECTIVES: Combined antiretroviral therapy (cART) attenuates hepatic fibrosis in
hepatitis C virus and HIV coinfected patients. However, the role of HIV or cART
on hepatic fibrosis in HIV monoinfection is discussed controversially. During
liver fibrosis, matrix metalloproteinases (MMPs) degrade extracellular matrix
(ECM) proteins into small soluble fragments, which reflect hepatic remodeling
processes. This study used these novel biomarkers to investigate the effect of
HIV and cART on hepatic fibrosis remodeling. DESIGN: In 249 patients with HIV
monoinfection and 55 healthy controls, the serum levels of MMP-degraded collagen
type III (C3M), biglycan (BGM), elastin (ELM), as well as the formation marker 7S
(P4NP 7S), and MMP-degraded collagen type IV (C4M) were determined using specific
ELISAs. Sixty-eight patients underwent a follow-up visit 3 years later including
assessment of ECM markers and fibrosis using transient elastography (Fibroscan).
RESULTS: C3M, BGM, C4M and P4NP 7S were significantly elevated in HIV patients
compared to controls and correlated to HIV viral loads and inversely to cART
duration. C4M, P4NP 7S and ELM were lower in patients under cART therapy and in
patients without HIV viremia, indicating that lowering of the HIV load by cART
attenuates remodeling of ECM. The levels of C3M, C4M, P4NP 7S and ELM correlated
significantly with the progression of fibrosis in these patients. CONCLUSION:
Specific therapy of patients with HIV monoinfection also beneficially influences
liver fibrosis. These novel markers of liver fibrosis remodeling may help to
monitor the hepatic effects by HIV therapy.
PMID- 25136934
TI - Functionalised nanoparticles complexed with antibiotic efficiently kill MRSA and
other bacteria.
AB - Antibiotic-resistant bacterial infections are a vexing global health problem and
have rendered ineffective many previously-used antibiotics. Here we demonstrate
that antibiotic-linkage to surface-functionalized silica nanoparticles (sNP)
significantly enhances their effectiveness against Escherichia coli, and
Staphylococcus aureus, and even methicillin-resistant S. aureus (MRSA) strains
that are resistant to most antibiotics. The commonly-used antibiotic penicillin-G
(PenG) was complexed to dye-labeled sNPs (15 nm diameter) containing carboxyl
groups located as either surface-functional groups, or on polymer-chains
extending from surfaces. Both sNPs configurations efficiently killed bacteria,
including MRSA strains. This suggests that activities of currently-ineffective
antibiotics can be restored by nanoparticle-complexation and used to avert
certain forms of antibiotic-resistance.
PMID- 25136935
TI - Subjective Health Complaints Among Workers in the Aftermath of an Oil Tank
Explosion.
AB - The aim of the study was to assess whether exposed workers had more subjective
health complaints than controls 1 1/2 years after a chemical explosion involving
a mixture of hydrocarbons and sulfurous compounds. A cross-sectional survey based
on the Subjective Health Complaints Inventory (SHC) was conducted among 147
exposed workers and 137 controls. A significantly higher total SCH score (linear
regression, p=.01) was found for the exposed workers compared with controls when
adjusting for gender, age, smoking habits, and educational level. The exposed
workers reported significantly more headache, hot flashes, sleep problems,
tiredness, dizziness, and sadness/depression. The cause of these complaints is
unknown, but health personnel should be aware that health complaints might be
related to polluting episodes even when exposure levels are below occupational
guideline levels.
PMID- 25136936
TI - What Does a Performance Measurement System Tell Us About the National
Comprehensive Cancer Control Program?
AB - CONTEXT: The National Comprehensive Cancer Control Program (NCCCP) performance
measurement system seeks to understand both the processes that funded programs
undertake with their respective coalitions to implement the objectives of their
cancer plans and the outcomes of those efforts. OBJECTIVE: To identify areas of
achievement and technical assistance needs of NCCCP awardees. DESIGN: Program
performance was assessed through surveys completed by program directors on
performance indicators in 2009 and 2010 and queries from a Web-based management
information system in 2011 and 2012. SETTING: Programs funded by the Centers for
Disease Control and Prevention's NCCCP. PARTICIPANTS: Sixty-nine programs. MAIN
OUTCOME MEASURE(S): The key performance measures assessed were inclusion of
diverse partners and key sectors in cancer coalitions, partners' involvement in
activities, receiving in-kind resources from partners, using evidence-based
interventions and data for setting priorities, conducting program evaluation,
using community- or organization-level strategies to address cancer control
efforts, and demonstrating progress toward achieving health outcomes. RESULTS:
Most programs reported having active coalitions that represent diverse
organizational sectors. Nearly all programs routinely assess the burden of
cancer. In-kind resources to implement activities peaked at $64 716 in the second
year of a 5-year funding cycle and declined in subsequent project years. By year
3, more than 70% of programs reported having an evaluation plan. While programs
reported that nearly two-thirds of their interventions were evidence-based, some
programs implemented non-evidence-based interventions. A majority of programs
successfully used at least 1 community- or organization-level change strategy.
However, many programs did not incorporate objectives linked to health outcomes
as they reported progress in implementing interventions. CONCLUSIONS: While NCCCP
programs were strong at building and maintaining infrastructure, some programs
may need additional technical assistance to increase the adoption of evidence
based interventions, develop solid and responsive evaluation plans, and better
link efforts to population-based measures that demonstrate impact toward reducing
the burden of cancer.
PMID- 25136937
TI - The diffusion of evidence-based decision making among local health department
practitioners in the United States.
AB - OBJECTIVES: Evidence-based decision making (EBDM) is the process, in local health
departments (LHDs) and other settings, of translating the best available
scientific evidence into practice. Local health departments are more likely to be
successful if they use evidence-based strategies. However, EBDM and use of
evidence-based strategies by LHDs are not widespread. Drawing on diffusion of
innovations theory, we sought to understand how LHD directors and program
managers perceive the relative advantage, compatibility, simplicity, and
testability of EBDM. DESIGN, SETTING, AND PARTICIPANTS: Directors and managers of
programs in chronic disease, environmental health, and infectious disease from
LHDs nationwide completed a survey including demographic information and
questions about diffusion attributes (advantage, compatibility, simplicity, and
testability) related to EBDM. Bivariate inferential tests were used to compare
responses between directors and managers and to examine associations between
participant characteristics and diffusion attributes. RESULTS: Relative advantage
and compatibility scores were high for directors and managers, whereas simplicity
and testability scores were lower. Although health department directors and
managers of programs in chronic disease generally had higher scores than other
groups, there were few significant or large differences between directors and
managers across the diffusion attributes. Larger jurisdiction population size was
associated with higher relative advantage and compatibility scores for both
directors and managers. CONCLUSIONS: Overall, directors and managers were in
strong agreement on the relative advantage of an LHD using EBDM, with directors
in stronger agreement than managers. Perceived relative advantage has been
demonstrated to be the most important factor in the rate of innovation adoption,
suggesting an opportunity for directors to speed EBDM adoption. However, lower
average scores across all groups for simplicity and testability may be hindering
EBDM adoption. Recommended strategies for increasing perceived EBDM simplicity
and testability are provided.
PMID- 25136938
TI - Electrospun polymer mat as a SERS platform for the immobilization and detection
of bacteria from fluids.
AB - This work demonstrates the development of a new class of SERS substrates that
allows for the simultaneous: (i) filtration of bacteria from any solution (blood,
urine, water, or milk), (ii) immobilization of bacteria on the SERS platform, and
(iii) enhancing the Raman signal of bacteria. The proposed platform is based on
an electrospun polymer mat covered with a 90 nm layer of gold.
PMID- 25136939
TI - Harms and benefits associated with exercise therapy for CFS/ME.
PMID- 25136940
TI - Elements of rehabilitative strategies associated with negative outcomes in
CFS/ME: the need for further investigations.
PMID- 25136941
TI - Residential immersive life skills programs for youth with disabilities: service
providers' perceptions of experiential benefits and key program features.
AB - PURPOSE: The objective was to determine service providers' perceptions of the
experiential benefits of residential immersive life skills (RILS) programs for
youth with disabilities, along with important program features. METHODS: Thirty
seven service providers from three RILS programs took part in qualitative
interviews. Themes were derived using a phenomenological approach. RESULTS: There
were perceived benefits for youth, and also for parents and service providers.
Study themes concerned the process of youth empowerment, life-changing
experiences for youth and parents, and changed service provider views affecting
practice. Youth changes were attributed to the residential group format and
afforded opportunities, which included being away from home, navigating public
transportation, directing attendant services, and sharing intense learning and
social experiences with peers. Youth were seen to experience important personal
changes in life skills, self-confidence, self-understandings, and self-advocacy.
Perceived benefits for parents included realizations concerning their child's
abilities and new hope for the future. Service providers indicated changes in
their knowledge, perspectives, and approach to practice. CONCLUSIONS: The
findings suggest that life skills programs should be intentionally designed to
provide challenging experiential opportunities that motivate youth to engage in
new life directions by providing new insights, self-realizations, and positive
yet realistic views of the future. IMPLICATIONS FOR REHABILITATION: Service
providers indicated the importance of challenging, real-world experiential
opportunities that provide youth with disabilities with new insights, self
realizations, and positive yet realistic views of the future. Important
experiential opportunities for youth included being away from home, navigating
public transportation, directing attendant care, and sharing intense learning and
social experiences with peers. The findings provide preliminary qualitative
evidence that life skills programs should be intentionally designed to provide
experiential opportunities that equip youth with knowledge, skills, and
confidence, and motivate them to engage in new life directions. Service providers
indicated important changes to their practice as a result of their involvement in
a RILS program, including adopting a more holistic and facilitative approach to
practice.
PMID- 25136943
TI - Surgery of primary lung cancer with oligometastatic m1b synchronous single brain
metastasis: analysis of 37 cases.
AB - BACKGROUND: At the time of diagnosis, lung cancer has often metastasized already.
Brain metastases, however, are associated with a poor prognosis (median survival
of less than 1 year). We evaluated the changes of the median survival after
resection of the cerebral metastases and primary non-small cell lung cancer
(NSCLC). MATERIALS AND METHODS: Between January 1999 and December 2009, 37
patients (22 men, 15 women; median age: 55.64 years; age range: 38-72 years)
underwent surgery for primary NSCLC after craniotomy and removal of the
synchronous single brain metastasis. The overall survival was evaluated and risk
factors identified. RESULTS: Mediastinal lymph node involvement was excluded with
mediastinoscopy in 26 of the 37 patients. Postoperative N-stage was N0, N1, and
N2 in 16 (43%), 10 (27%), and 11 (30%) patients, respectively. Histology was
squamous cell carcinoma in 10 (27%), adenocarcinoma in 20 (54%), and large cell
carcinoma in 7 (19%). The employed type of resection was anatomical segmentectomy
in 6 and lobectomy in 31 patients. The 30-day mortality was 0% and postoperative
complications occurred in 12 patients only (32%). The overall 1 and 2 years
survival were 62 and 24%, respectively. None of the factors age, sex, tumor
histology, primary location of the tumor, type of resection, adjuvant
chemotherapy, or nodal status affected survival in the univariate analysis.
CONCLUSIONS: The oncologic lung resection of NSCLC after the resection of a
single brain metastasis can be implemented without an increased risk of
complications or mortality. Despite the stage IV disease, the median survival
appears encouraging.
PMID- 25136944
TI - Cardiomegaly Is a Significant Predictor of Postoperative Atelectasis following
Left Upper Superior Segmentectomy.
AB - BACKGROUND: Segmentectomy is becoming more common since many lung cancers are
small when found. Left upper superior segmentectomy (LUSS) is the most popular
procedure for segmentectomy. Atelectasis is a common postoperative complication
following segmentectomy. In this study, we sought to better understand
atelectasis of the lingular segment following LUSS. MATERIALS AND METHODS: Among
265 patients who underwent segmentectomy of the lung at our institute between
February 2008 and August 2012, 60 patients who underwent LUSS were investigated
retrospectively. An intersegmental plane was created using a stapler in 41 and by
cautery in 19. The relationships between atelectasis of the lingular segment and
clinical factors were analyzed by multivariate analysis. The clinical factors
examined included body mass index, preoperative cardio/thoracic dimension ratio
(CTR), preoperative forced expiratory volume in 1 second (FEV1), the method used
to make an intersegmental plane, the interval of thoracic drainage, and the
degree of lobulation. RESULTS: Atelectasis of the lingular segment was seen in
nine (15.0%) patients. Preoperative CTR predicted atelectasis of the lingular
segment (p = 0.004). FEV1 was preserved in 73.8% of patients with atelectasis of
the lingular segment and in 86.8% of the controls. This difference was
significant (p = 0.027). Atelectasis of the middle lobe following RUL was seen in
10/238 (4.2%) within the same period. CONCLUSIONS: Preoperative CTR was related
to atelectasis of the lingular segment. One of the advantages of segmentectomy is
that it enables the postoperative preservation of respiratory function. However,
in patients with cardiomegaly, respiratory function following LUSS may be
preserved less than expected.
PMID- 25136945
TI - Novel thoughts on patient-prosthesis mismatch in aortic valve replacement: the
rationale for the PAR I trial.
AB - The hemodynamic performance of prosthetic tissue valves is influenced by valve
design and valve-specific sizing strategies. Design determines the actual
geometric opening area (GOA) of the prosthetic valve and sizing strategy its
actual chosen size. Currently, hemodynamic performance is assessed by determining
the effective orifice area (EOA; derived from the continuity equation by relating
flow velocities with the area of the left ventricular outflow tract [LVOTA]). The
question whether a valve is too small (patient-prosthesis mismatch [PPM]) is
currently addressed by relating EOA to body surface area (EOA index [EOAi]).
However, this relation may not be appropriate because the EOAi relates flow
velocity to patient-specific anatomic parameters twice (i.e., LVOTA and body
surface area). This potential confounder may explain the controversies regarding
PPM. However, intuitively, leaving a gradient behind after aortic valve
replacement cannot be irrelevant. PPM becomes even more relevant with
transcatheter valve-in-valve implantation, where a second prosthesis is taking up
inner space of a valve that may have already been too small initially. Thus, a
reliable method to determine the presence of PPM is needed. The Prosthesis-to
Annulus Relation I (PAR I) trial is a German multicenter study assessing the
relation between the prosthetic GOA and the LVOTA as a potentially new parameter
for the prediction of hemodynamic outcome. The results may possibly guide future
valve size selection and may allow prediction of functionally relevant PPM. Here,
we will demonstrate the shortcomings of the currently applied EOAi for the
assessment of hemodynamic relevance and present the rationale for the PARI trial,
which recently started recruiting patients.
PMID- 25136946
TI - Pediatric prenatal diagnosis of congenital heart disease.
AB - PURPOSE OF REVIEW: Fetal cardiology is a rapidly evolving field. Imaging
technology continues to advance as do approaches to in-utero interventions and
care of the critically ill neonate, with even greater demand for improvement in
prenatal diagnosis of congenital heart disease (CHD) and arrhythmias. RECENT
FINDINGS: Reviewing the advances in prenatal diagnosis of CHD in such a rapidly
developing field is a broad topic. Therefore, we have chosen to focus this review
of recent literature on challenges in prenatal detection of CHD, challenges in
prenatal counseling, advances in fetal arrhythmia diagnosis, and potential
benefits to patients with CHD who are identified prenatally. SUMMARY: As methods
and tools to diagnose and manage CHD and arrhythmias in utero continue to
improve, future generations will hopefully see a reduction in both prenatal and
neonatal morbidity and mortality. Prenatal diagnosis can and should be used to
optimize location and timing of delivery and postnatal interventions.
PMID- 25136948
TI - Pertussis: still a cause of death, seven decades into vaccination.
AB - PURPOSE OF REVIEW: We review the resurgence of pertussis, including recent trends
in epidemiology and reasons for the resurgence, as well as updated vaccination
schedules and recommendations. RECENT FINDINGS: There has been a resurgence of
pertussis in recent decades, in the United States and worldwide. This is a
preventable cause of hospitalizations and deaths, especially among the infant
population. Possible reasons for the resurgence include increased awareness via
surveillance and reporting, diagnostic testing improvements, infant
susceptibility coupled with exposure to infected caregivers, waning immunity
despite complete vaccination, inferior long-term efficacy of acellular vaccines
compared with whole-cell vaccines, circulating mutant strains of the bacterium,
and parents refusing vaccination of their children. Progressively updated vaccine
recommendations should be adhered to, as this is currently the only available
tool to stem the public health challenge. SUMMARY: The resurgence of pertussis is
a multifaceted problem, but the implementation of immunization for all age groups
is of utmost importance.
PMID- 25136947
TI - Progress in the diagnosis and management of pulmonary hypertension in children.
AB - PURPOSE OF REVIEW: Pulmonary hypertension is a complex disease that extends
beyond merely elevated pulmonary blood pressures and right ventricular
dysfunction. Its multiple causes and ever-expanding diagnostic tools and
therapeutic approaches make it a heterogeneous disease with widely variable
clinical sequelae. There are still many unanswered questions that challenge our
understanding of this disease. RECENT FINDINGS: The study of pulmonary
hypertension in the pediatric patient is as robust as ever, with the creation and
inclusion of pediatric-specific disease characteristics in the most recent WHO
classification system, improved understanding of the pathophysiology of pulmonary
hypertension in pediatric diseases such as bronchopulmonary dysplasia, and
increasingly expanding diagnostic tools and management possibilities. Although
the use of pulmonary hypertension therapies in children previously often relied
on expert opinion and inferences from studies involving adults, pediatric
targeted research is becoming more widely supported and pursued, and has even
come under recent debate, which at the very least stimulates further
collaboration and discussion. SUMMARY: This review will highlight the changes in
the pulmonary hypertension classification system, briefly explore pulmonary
hypertension in bronchopulmonary dysplasia, and provide updates on the diagnostic
and management tools used by experts in the field.
PMID- 25136950
TI - The polar high molecular weight fraction of the Agaricus blazei Murill extract,
AndoSanTM, reduces the activity of the tumor-associated protease, legumain, in
RAW 264.7 cells.
AB - AndoSanTM is an extract of Agaricus blazei Murill (AbM; 82.4%), Hericium
erinaceum (14.7%), and Grifola frondosa (2.9%). The main ingredient of AndoSan,
AbM, is rich in different forms of beta-glucans. Since these exhibit potent
antitumor activity and have immunomodulatory effects, the stimulatory effect of
AndoSan on the production of different cytokines, chemokines, and leukocyte
growth factors has predominantly been attributed to beta-glucans. AndoSan has
been claimed to consist of 90% carbohydrate, of which 2.8% is beta-glucans, but
in this study, we show that the carbohydrate content is only 2% of the dry
weight, corresponding to 0.09% beta-glucan per mL of AndoSan. Fractionation of
AndoSan, followed by carbohydrate analysis and HPLC analysis revealed that most
of the glucose was concentrated in the polar high molecular weight fraction of
AndoSan (ethanol insoluble water extract [EIWE]-A) and that this extract was able
to significantly inhibit the activity of the tumor-associated protease, legumain,
in RAW 264.7 cells. Legumain is synthesized as a zymogen and undergoes pH
dependent autoactivation of the proform to reach an enzymatically active form. In
this study, we demonstrate that both the polar and nonpolar AndoSan fractions are
able to inhibit the autoactivation of prolegumain, and that the polar fractions
of AndoSan are the most potent inhibitors of the active form of the enzyme.
PMID- 25136951
TI - Measurement of cardiac index by transpulmonary thermodilution using an implanted
central venous access port: a prospective study in patients scheduled for
oncologic high-risk surgery.
AB - BACKGROUND: Transpulmonary thermodilution allows the measurement of cardiac index
for high risk surgical patients. Oncologic patients often have a central venous
access (port-a-catheter) for chronic treatment. The validity of the measurement
by a port-a-catheter of the absolute cardiac index and the detection of changes
in cardiac index induced by fluid challenge are unknown. METHODS: We conducted a
monocentric prospective study. 27 patients were enrolled. 250 ml colloid volume
expansions for fluid challenge were performed during ovarian cytoreductive
surgery. The volume expansion-induced changes in cardiac index measured by
transpulmonary thermodilution by a central venous access (CIcvc) and by a port-a
catheter (CIport) were recorded. RESULTS: 23 patients were analyzed with 123
pairs of measurements. Using a Bland and Altman for repeated measurements, the
bias (lower and upper limits of agreement) between CIport and CIcvc was 0.14 (
0.59 to 0.88) L/min/m2. The percentage error was 22%. The concordance between the
changes in CIport and CIcvc observed during volume expansion was 92% with an r =
0.7 (with exclusion zone). No complications (included sepsis) were observed
during the follow up period. CONCLUSIONS: The transpulmonary thermodilution by a
port-a-catheter is reliable for absolute values estimation of cardiac index and
for measurement of the variation after fluid challenge. TRIAL REGISTRATION:
clinicaltrials.gov NCT02063009.
PMID- 25136957
TI - Self-assembled Fe3O4/polymer hybrid microbubble with MRI/ultrasound dual-imaging
enhancement.
AB - An Fe3O4 nanoparticle/polymer hybrid microbubble was developed using a facile
self-assembly approach. This approach involves two steps, including the initial
fabrication of the iron oxide nanoparticle (IONP)/polymer hybrid microcapsules
via self-assembly and a subsequent gas-filling process to yield the final
microbubbles. Both in vitro and in vivo experiments demonstrated that the
composite gas-filled microbubbles exhibit excellent T2-weighted magnetic
resonance imaging (MRI) enhancement as well as ultrasound (US) imaging
enhancement capabilities. Besides, this flexible approach allows the facile
control of the microbubbles' size and thus the imaging capabilities of the
microbubbles through the tuning of the molar ratio between the precursors.
PMID- 25136952
TI - Selective HDAC inhibition for the disruption of latent HIV-1 infection.
AB - Selective histone deacetylase (HDAC) inhibitors have emerged as a potential anti
latency therapy for persistent human immunodeficiency virus type 1 (HIV-1)
infection. We utilized a combination of small molecule inhibitors and short
hairpin (sh)RNA-mediated gene knockdown strategies to delineate the key HDAC(s)
to be targeted for selective induction of latent HIV-1 expression. Individual
depletion of HDAC3 significantly induced expression from the HIV-1 promoter in
the 2D10 latency cell line model. However, depletion of HDAC1 or -2 alone or in
combination did not significantly induce HIV-1 expression. Co-depletion of HDAC2
and -3 resulted in a significant increase in expression from the HIV-1 promoter.
Furthermore, concurrent knockdown of HDAC1, -2, and -3 resulted in a significant
increase in expression from the HIV-1 promoter. Using small molecule HDAC
inhibitors of differing selectivity to ablate the residual HDAC activity that
remained after (sh)RNA depletion, the effect of depletion of HDAC3 was further
enhanced. Enzymatic inhibition of HDAC3 with the selective small-molecule
inhibitor BRD3308 activated HIV-1 transcription in the 2D10 cell line.
Furthermore, ex vivo exposure to BRD3308 induced outgrowth of HIV-1 from resting
CD4+ T cells isolated from antiretroviral-treated, aviremic HIV+ patients. Taken
together these findings suggest that HDAC3 is an essential target to disrupt HIV
1 latency, and inhibition of HDAC2 may also contribute to the effort to purge and
eradicate latent HIV-1 infection.
PMID- 25136958
TI - Characterization of a cross-reactive, immunodominant and HLA-promiscuous epitope
of Mycobacterium tuberculosis-specific major antigenic protein PPE68.
AB - PPE68 (Rv3873), a major antignic protein encoded by Mycobacteriun tuberculosis
specific genomic region of difference (RD)1, is a strong stimulator of peripheral
blood mononuclear cells (PBMCs) obtained from tuberculosis patients and
Mycobacterium bovis bacillus Calmette Guerin (BCG)-vaccianted healthy subjects in
T helper (Th)1 cell assays, i.e. antigen-induced proliferation and interferon
gamma (IFN-gamma) secretion. To confirm the antigen-specific recognition of PPE68
by T cells in IFN-gamma assays, antigen-induced human T-cell lines were
established from PBMCs of M. Bovis BCG-vaccinated and HLA-heterogeneous healthy
subjects and tested with peptide pools of RD1 proteins. The results showed that
PPE68 was recognized by antigen-specific T-cell lines from HLA-heteregeneous
subjects. To further identify the immunodominant and HLA-promiscuous Th1-1 cell
epitopes present in PPE68, 24 synthetic peptides covering the sequence of PPE68
were indivdually analyzed for HLA-DR binding prediction analysis and tested with
PBMCs from M. bovis BCG-vaccinated and HLA-heterogeuous healthy subjects in IFN
gamma assays. The results identified the peptide P9, i.e. aa 121
VLTATNFFGINTIPIALTEMDYFIR-145, as an immunodominant and HLA-DR promiscuous
peptide of PPE68. Furthermore, by using deletion peptides, the immunodominant and
HLA-DR promiscuous core sequence was mapped to aa 127-FFGINTIPIA-136.
Interestingly, the core sequence is present in several PPE proteins of M.
tuberculosis, and conserved in all sequenced strains/species of M. tuberculosis
and M. tuberculosis complex, and several other pathogenic mycobacterial species,
including M. leprae and M. avium-intracellulalae complex. These results suggest
that the peptide aa 121-145 may be exploited as a peptide-based vaccine candidate
against tuberculosis and other mycobacterial diseases.
PMID- 25136959
TI - Inside money, procyclical leverage, and banking catastrophes.
AB - We explore a model of the interaction between banks and outside investors in
which the ability of banks to issue inside money (short-term liabilities believed
to be convertible into currency at par) can generate a collapse in asset prices
and widespread bank insolvency. The banks and investors share a common belief
about the future value of certain long-term assets, but they have different
objective functions; changes to this common belief result in portfolio
adjustments and trade. Positive belief shocks induce banks to buy risky assets
from investors, and the banks finance those purchases by issuing new short-term
liabilities. Negative belief shocks induce banks to sell assets in order to
reduce their chance of insolvency to a tolerably low level, and they supply more
assets at lower prices, which can result in multiple market-clearing prices. A
sufficiently severe negative shock causes the set of equilibrium prices to
contract (in a manner given by a cusp catastrophe), causing prices to plummet
discontinuously and banks to become insolvent. Successive positive and negative
shocks of equal magnitude do not cancel; rather, a banking catastrophe can occur
even if beliefs simply return to their initial state. Capital requirements can
prevent crises by curtailing the expansion of balance sheets when beliefs become
more optimistic, but they can also force larger price declines. Emergency asset
price supports can be understood as attempts by a central bank to coordinate
expectations on an equilibrium with solvency.
PMID- 25136961
TI - A model for implementing guidelines for person-centered care in a nursing home
setting.
AB - BACKGROUND: Systematic evaluations of knowledge translation interventions in
nursing homes to improve practice are scarce. There is also a lack of studies
focusing on creating sustainable evidence-based practice in the setting of
residential dementia care. METHODS: The aim of this paper is to describe a model
for implementing national evidence-based guidelines for care of persons with
dementia in nursing homes. The secondary aim is to outline the nursing home staff
experiences during the first year of the implementation process. The intervention
had a participatory action research approach. This included educational
activities such as: (i) thematic seminars introducing national guidelines for
dementia care, (ii) regular unit-based seminars; and (iii) later dissemination of
information in reflective seminars and several days of poster-exhibitions. Areas
of practice development were selected on each of the 24 units, based on unit
specific needs, and a quality improvement strategy was applied and evaluated.
Each unit met ten times during a period of eight months. Data for this study were
extracted from the reflective seminars and poster presentations, analyzed using a
qualitative content analysis. RESULTS: Findings showed that implementation of
guidelines were perceived by staff as beneficial for both staff and the
residents. However, barriers to identification of relevant sources of evidence
and barriers to sustainable implementation were experienced. CONCLUSIONS: One of
our assumptions was that dementia nursing homes can benefit from becoming
knowledge driven, with care practices founded in evidence-based sources. Our
findings show that to be partly true, even though most staff units found their
efforts to pursue and utilize knowledge adversely impacted by time-logistics and
practical workload challenges.
PMID- 25136960
TI - Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyclin A and
cdk2.
AB - Amygdalin, a natural compound, has been used by many cancer patients as an
alternative approach to treat their illness. However, whether or not this
substance truly exerts an anti-tumor effect has never been settled. An in vitro
study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml) on
the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP).
Tumor growth, proliferation, clonal growth and cell cycle progression were
investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A,
cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR)
related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined.
Amygdalin dose-dependently reduced growth and proliferation in all three bladder
cancer cell lines, reflected in a significant delay in cell cycle progression and
G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor
and loss of Cdk and cyclin components. Since the most outstanding effects of
amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were
carried out, revealing a positive correlation between cdk2/cyclin A expression
level and tumor growth. Amygdalin, therefore, may block tumor growth by down
modulating cdk2 and cyclin A. In vivo investigation must follow to assess
amygdalin's practical value as an anti-tumor drug.
PMID- 25136962
TI - Costing of commune health station visits for provider payment reform in Vietnam.
AB - Expanding effective coverage in Vietnam will require better use of available
resources and placing higher priority on primary care. The way providers are
currently paid does not give priority to primary care and does not reflect the
costs of delivering services. This paper aims to estimate the unit costs of
primary care visits at commune health stations (CHS) in selected areas in
Vietnam. Seventy-six CHS from two provinces in northern Vietnam were studied.
Costs were calculated from the perspective of the CHS using the top-down costing
using the step-down cost accounting technique in order to estimate the full cost
of delivering services. On average, the cost of one outpatient visit in
mountainous, rural and urban CHSs was VND 49,521 (US$2.40), VND 41,375 (US$2.01)
and VND 39,794 (US$1.93), respectively. Personnel costs accounted for the highest
share of total costs followed by medicines. The share of operating costs was
minimal. On average, CHSs recover 18.9% of their total cost for an outpatient
visit from social insurance payments or fees that can be charged patients. The
results provide valuable information for policy-makers as they revise the
provider payment methods to better reflect the costs of services and give greater
priority to primary care.
PMID- 25136964
TI - The effect of insulin resistance on breast cancer risk in Latinas of Mexican
origin.
AB - BACKGROUND: Conclusive evidence has yet to emerge regarding the association
between markers of hyperinsulinemia and breast cancer. We determined the effect
of insulin resistance (IR) on breast cancer risk in Latinas of Mexican origin who
did not have a direct family history of breast cancer and had not been previously
diagnosed with prediabetes or diabetes. METHODS: This was a case-control study in
which a case (n=124) was defined as a patient with a recent histopathologic
diagnosis of breast cancer and a control (n=197) was defined as a participant who
had recently undergone a mammography and had either a Breast Imaging, Reporting &
Data System (BI-RADS)-1 or a BI-RADS-2 score. Plasma glucose, insulin, and
glycated hemoglobin (HbA1c) levels were measured. IR was determined by using the
homeostasis model assessment (HOMA-IR) criterion. Odds ratios (OR) and 95%
confidence intervals (CI) were determined using unconditional binary logistic
regression analysis. RESULTS: IR was detected in 33.9% of cases and 41.6% of
controls, based on a HOMA-IR >=3.5. Although multivariate analysis did not show
any association between IR and breast cancer risk (OR 0.56, 95% CI 0.31-1.01), it
showed that an HbA1c >=5.7% increased the risk of breast cancer (OR 3.41, 95% CI
1.93-6.01), regardless of menopausal status. CONCLUSIONS: The findings suggest
that IR had no effect on breast cancer risk; however HbA1c increased the risk in
Latinas of Mexican origin who had not been diagnosed previously with prediabetes
or diabetes and had no direct family history of breast cancer. Prospective
studies are required to establish the impact of IR over time.
PMID- 25136963
TI - Transcriptional profiling in rat hair follicles following simulated Blast insult:
a new diagnostic tool for traumatic brain injury.
AB - With wide adoption of explosive-dependent weaponry during military activities,
Blast-induced neurotrauma (BINT)-induced traumatic brain injury (TBI) has become
a significant medical issue. Therefore, a robust and accessible biomarker system
is in demand for effective and efficient TBI diagnosis. Such systems will also be
beneficial to studies of TBI pathology. Here we propose the mammalian hair
follicles as a potential candidate. An Advanced Blast Simulator (ABS) was
developed to generate shock waves simulating traumatic conditions on brains of
rat model. Microarray analysis was performed in hair follicles to identify the
gene expression profiles that are associated with shock waves. Gene set
enrichment analysis (GSEA) and sub-network enrichment analysis (SNEA) were used
to identify cell processes and molecular signaling cascades affected by simulated
bomb blasts. Enrichment analyses indicated that genes with altered expression
levels were involved in central nervous system (CNS)/peripheral nervous system
(PNS) responses as well as signal transduction including Ca2+, K+-transportation
dependent signaling, Toll-Like Receptor (TLR) signaling and Mitogen Activated
Protein Kinase (MAPK) signaling cascades. Many of the pathways identified as
affected by shock waves in the hair follicles have been previously reported to be
TBI responsive in other organs such as brain and blood. The results suggest that
the hair follicle has some common TBI responsive molecular signatures to other
tissues. Moreover, various TBI-associated diseases were identified as
preferentially affected using a gene network approach, indicating that the hair
follicle may be capable of reflecting comprehensive responses to TBI conditions.
Accordingly, the present study demonstrates that the hair follicle is a
potentially viable system for rapid and non-invasive TBI diagnosis.
PMID- 25136966
TI - Development of multidrug resistant tuberculosis in Bangladesh: a case-control
study on risk factors.
AB - OBJECTIVE: To determine the risk factors for developing multidrug resistant
tuberculosis in Bangladesh. METHODS: This case-control study was set in central,
district and sub-district level hospitals of rural and urban Bangladesh. Included
were 250 multidrug resistant tuberculosis (MDR-TB) patients as cases and 750 drug
susceptible tuberculosis patients as controls. We recruited cases from all three
government hospitals treating MDR-TB in Bangladesh during the study period.
Controls were selected randomly from those local treatment units that had
referred the cases. Information was collected through face-to-face interviews and
record reviews. Unadjusted and multivariable logistic regression were used to
analyse the data. RESULTS: Previous treatment history was shown to be the major
contributing factor to MDR-TB in univariate analysis. After adjusting for other
factors in multivariable analysis, age group "18-25" (OR 1.77, CI 1.07-2.93) and
"26-45" (OR 1.72, CI 1.12-2.66), some level of education (OR 1.94, CI 1.32-2.85),
service and business as occupation (OR 2.88, CI 1.29-6.44; OR 3.71, CI 1.59-8.66,
respectively), smoking history (OR 1.58, CI 0.99-2.5), and type 2 diabetes (OR
2.56 CI 1.51-4.34) were associated with MDR-TB. Previous treatment was not
included in the multivariable analysis as it was correlated with multiple
predictors. CONCLUSION: Previous tuberculosis treatment was found to be the major
risk factor for MDR-TB. This study also identified age 18 to 45 years, some
education up to secondary level, service and business as occupation, past smoking
status, and type 2 diabetes as comorbid illness as risk factors. National
Tuberculosis programme should address these risk factors in MDR-TB control
strategy. The integration of MDR-TB control activities with diabetes and tobacco
control programmes is needed in Bangladesh.
PMID- 25136965
TI - Built environment change and change in BMI and waist circumference: Multi-ethnic
Study of Atherosclerosis.
AB - OBJECTIVE: To examine longitudinal associations of the neighborhood built
environment with objectively measured body mass index (BMI) and waist
circumference (WC) in a geographically and racial/ethnically diverse group of
adults. METHODS: This study used data from 5,506 adult participants in the Multi
Ethnic Study of Atherosclerosis, aged 45-84 years in 2000 (baseline). BMI and WC
were assessed at baseline and four follow-up visits (median follow-up 9.1 years).
Time-varying built environment measures (population density, land-use,
destinations, bus access, and street characteristics) were created using
Geographic Information Systems. Principal components analysis was used to derive
composite scores for three built environment factors. Fixed-effects models,
tightly controlling for all time-invariant characteristics, estimated
associations between change in the built environment, and change in BMI and WC.
RESULTS: Increases in the intensity of development (higher density of walking
destinations and population density, and lower percent residential) were
associated with less pronounced increases or decreases over time in BMI and WC.
Changes in connected retail centers (higher percent retail, higher street
connectivity) and public transportation (distance to bus) were not associated
with changes in BMI or WC. CONCLUSIONS: Longitudinal changes in the built
environment, particularly increased density, are associated with decreases in BMI
and WC.
PMID- 25136967
TI - Age-stratified 5-year risks of cervical precancer among women with enrollment and
newly detected HPV infection.
AB - It is unclear whether a woman's age influences her risk of cervical
intraepithelial neoplasia grade 3 or worse (CIN3+) upon detection of HPV. A large
change in risk as women age would influence vaccination and screening policies.
Among 972,029 women age 30-64 undergoing screening with Pap and HPV testing
(Hybrid Capture 2, Qiagen, Germantown, MD) at Kaiser Permanente Northern
California (KPNC), we calculated age-specific 5-year CIN3+ risks among women with
HPV infections detected at enrollment, and among women with "newly detected" HPV
infections at their second screening visit. Women (57,899, 6.0%) had an
enrollment HPV infection. Among the women testing HPV negative at enrollment with
a second screening visit, 16,724 (3.3%) had a newly detected HPV infection at
their second visit. Both enrollment and newly detected HPV rates declined with
age (p < 0.001). Women with enrollment versus newly detected HPV infection had
higher 5-year CIN3+ risks: 8.5% versus 3.9%, (p < 0.0001). Risks did not increase
with age but declined slightly from 30-34 years to 60-64 years: 9.4% versus 7.4%
(p = 0.017) for enrollment HPV and 5.1% versus 3.5% (p = 0.014) for newly
detected HPV. Among women age 30-64 in an established screening program, women
with newly detected HPV infections were at lower risk than women with enrollment
infections, suggesting reduced benefit vaccinating women at older ages. Although
the rates of HPV infection declined dramatically with age, the subsequent CIN3+
risks associated with HPV infection declined only slightly. The CIN3+ risks among
older women are sufficiently elevated to warrant continued screening through age
65.
PMID- 25136968
TI - Characterizing of functional human coding RNA editing from evolutionary,
structural, and dynamic perspectives.
AB - A-to-I RNA editing has been recently shown to be a widespread phenomenon with
millions of sites spread in the human transcriptome. However, only few are known
to be located in coding sequences and modify the amino acid sequence of the
protein product. Here, we used high-throughput data, variant prediction tools,
and protein structural information in order to find structural and functional
preferences for coding RNA editing. We show that RNA editing has a unique pattern
of amino acid changes characterized by enriched stop-to-tryptophan changes,
positive-to-neutral and neutral-to-positive charge changes. RNA editing tends to
have stronger structural effect than equivalent A-to-G SNPs but weaker effect
than random A-to-G mutagenesis events. Sites edited at low level tend to be
located at conserved positions with stronger predicted deleterious effect on
proteins comparing to sites edited at high frequencies. Lowly edited sites tend
to destabilize the protein structure and affect amino acids with larger number of
intra-molecular contacts. Still, some highly edited sites are predicted also to
prominently affect structure and tend to be located at critical positions of the
protein matrix and are likely to be functionally important. Using our pipeline,
we identify and discuss several novel putative functional coding changing editing
sites in the genes COPA (I164V), GIPC1 (T62A), ZN358 (K382R), and CCNI (R75G).
PMID- 25136969
TI - Molecular cloning and characterization of a SID-1-like gene in Plutella
xylostella.
AB - RNA interference (RNAi) signal can spread from the point where the double
stranded RNA (dsRNA) was initially applied to other cells or tissues. SID-related
genes in Caenorhabditis elegans help in the spreading of this signal. However,
the mechanisms of systemic RNAi are still not unveiled in insects. In this study,
we cloned a full-length cDNA of sid-1-like gene, Pxylsid-1, from Plutella
xylostella that contains 1,047 bp opening reading frame encoding a putative
protein of 348 amino acids. This transcript is very much similar to the sil-1 in
Bombyx mori (68.8%). The higher expression levels of Pxylsid-1 were found at the
adult and fourth-instar stages compared to the second-instar stage with 21.48-
and 10.36-fold increase, respectively. Its expression levels in different tissues
were confirmed with the highest expression in the hemolymph, which showed 21.09
fold increase than the midgut; however it was lower in other tissues. The result
of RNAi by feeding bacterially expressed dsRNA targeting Pxylace-1, which showed
that the mRNA level of Pxylace-1 decreased by 34.52 and 64.04% after 36- and 72-h
treatment, respectively. However, the mRNA level of Pxylsid-1 was not
significantly induced when the Pxylace-1 was downregulated. Furthermore, we found
that downregulation of Pxylsid-1 did not affect the RNAi effect of Pxylace-1.
Hence, the Pxylsid-1 may not be involved in absorption of dsRNA from the midgut
fluid. A further study is needed to uncover the function of Pxylsid-1.
PMID- 25136971
TI - Accuracy of semiquantitative dynamic contrast-enhanced MRI for differentiating
type II from type I endometrial carcinoma.
AB - PURPOSE: To investigate type II endometrial carcinoma characterization using
dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and evaluate the
diagnostic accuracy of semiquantitative DCE-MRI in differentiating type II from
type I tumors. MATERIALS AND METHODS: Seventy-seven patients with endometrial
carcinoma were retrospectively evaluated using 3T DCE-MRI. The maximum absolute
enhancement of signal intensity (SImax), maximum relative enhancement (SIrel),
wash-in rate (WIR), and the SImax/SI (piriformis) ratio were analyzed. To
differentiate type I from type II tumors, optimal threshold criteria were
established. The Mann-Whitney U-test was used for statistical comparison and
receiver operating characteristic curve analysis was used to determine optimal
cutoff values. RESULTS: The SIrel (P < 0.001), WIR (P < 0.0001), and SImax/SI
(piriformis) ratio (P < 0.0001), but not SImax, differed significantly between
type I and type II carcinomas. Cutoff values of SIrel >=58.8, WIR >=37.0, and
SImax/SI (piriformis) ratio >=1.55 had sensitivities of 93%, 93%, and 67%,
specificities of 60%, 60%, and 79%, accuracies of 66%, 66%, and 67%,
respectively, for predicting type II endometrial carcinoma. CONCLUSION:
Endometrial carcinoma with strong (high level) enhancement on DCE-MRI is
suggestive of type II endometrial carcinoma. Semiquantitative evaluation of DCE
MRI may be useful for differentiating type II from type I tumors.
PMID- 25136970
TI - Bistable expression of virulence genes in salmonella leads to the formation of an
antibiotic-tolerant subpopulation.
AB - Phenotypic heterogeneity can confer clonal groups of organisms with new
functionality. A paradigmatic example is the bistable expression of virulence
genes in Salmonella typhimurium, which leads to phenotypically virulent and
phenotypically avirulent subpopulations. The two subpopulations have been shown
to divide labor during S. typhimurium infections. Here, we show that
heterogeneous virulence gene expression in this organism also promotes survival
against exposure to antibiotics through a bet-hedging mechanism. Using
microfluidic devices in combination with fluorescence time-lapse microscopy and
quantitative image analysis, we analyzed the expression of virulence genes at the
single cell level and related it to survival when exposed to antibiotics. We
found that, across different types of antibiotics and under concentrations that
are clinically relevant, the subpopulation of bacterial cells that express
virulence genes shows increased survival after exposure to antibiotics.
Intriguingly, there is an interplay between the two consequences of phenotypic
heterogeneity. The bet-hedging effect that arises through heterogeneity in
virulence gene expression can protect clonal populations against avirulent
mutants that exploit and subvert the division of labor within these populations.
We conclude that bet-hedging and the division of labor can arise through
variation in a single trait and interact with each other. This reveals a new
degree of functional complexity of phenotypic heterogeneity. In addition, our
results suggest a general principle of how pathogens can evade antibiotics:
Expression of virulence factors often entails metabolic costs and the resulting
growth retardation could generally increase tolerance against antibiotics and
thus compromise treatment.
PMID- 25136972
TI - Metabolomic profiling of serum in the progression of Alzheimer's disease by
capillary electrophoresis-mass spectrometry.
AB - There is high interest in the discovery of early diagnostic biomarkers of
Alzheimer's disease, for which metabolomics exhibits a great potential. In this
work, a metabolomic approach based on ultrafiltration and analysis by CE-MS has
been used to obtain representative fingerprints of polar metabolites from serum
samples in order to distinguish between patients with Alzheimer's disease, mild
cognitive impairment, and healthy controls. By the use of partial least squares
discriminant analysis it was possible to classify patients according to the
disease stage and then identify potential markers. Significant increase was
observed with progression of disease in levels of choline, creatinine, asymmetric
dimethyl-arginine, homocysteine-cysteine disulfide, phenylalanyl-phenylalanine,
and different medium chain acylcarnitines. On the other hand, asparagine,
methionine, histidine, carnitine, acetyl-spermidine, and C5-carnitine were
reduced in these serum samples. In this way, multiple essential pathways were
found implicated in the underlying pathology, such as oxidative stress or defects
in energy metabolism. However, the most interesting results are related to the
association of several vascular risk factors with Alzheimer's disease.
PMID- 25136973
TI - Photoredox-catalyzed tandem radical cyclization of N-arylacrylamides: general
methods to construct fluorinated 3,3-disubstituted 2-oxindoles using
fluoroalkylsulfonyl chlorides.
AB - Fluorinated radicals were generated from RfSO2Cl by photoredox catalysis under
mild conditions, where Rf = n-C4F9, CF3, CF2H, CH2F, CH2CF3, and CF2CO2Me. This
method provided a general way to construct fluorinated 2-oxindoles from reaction
with N-arylacrylamides via a proposed tandem radical cyclization process.
PMID- 25136974
TI - Facing the challenges of chronic pruritus: a report from a multi-disciplinary
medical itch centre in Germany.
AB - The complex nature and difficult-to-establish aetiology of chronic pruritus (CP)
makes it challenging to provide medical care for patients with CP. This challenge
can only be met with a multidisciplinary approach. The first multidisciplinary
Itch Centre in Germany was established at the University of Munster in 2002 to
meet the needs of this patient population. More than 2,500 outpatients and 400
inpatients are diagnosed and receive treatment each year. To ensure evidence
based medical care, an electronic system for medical documentation and patient
reported outcomes was established. Automated data transfer to a research database
enables comprehensive data analysis. Our translational research has characterized
peripheral and central itch mechanisms, provided novel clustering of CP patients,
and identified novel target-specific therapies (e.g. neurokinin 1 receptor
antagonist). The multidisciplinary approach, combined with basic, clinical and
translational research, enables comprehensive medical care of patients as well as
implementation of high-quality experimental and clinical studies.
PMID- 25136975
TI - Shell-programmed Au nanoparticle heterodimers with customized chiroptical
activity.
AB - Chiral plasmonic assemblies with strong and tunable chiroptical activity are
emerging materials yet challenging to fabricate. Moreover, shell-programmed
chiroptical regulation is really rare. Here, the chiroptical activity of core
shell (CS) nanoparticles (NPs) heterodimers (HDs) with different types and
thicknesses of the shell but featuring the same gap was exploited. It was found
that the type of shell guided the position of the chiral peaks, and the shell
thickness tuned the intensity but also moderately affected the wavelength shift
at invariable interparticle distance. Shell deposition intensified the hot-spot
chirality, and evidently guided the enantiomorphous chiral configuration,
resulting in a startlingly intense, asymmetric, dipolar coupling strength. The
magnitude of the chiroptical activity showed an 8-10 fold enhancement with a
maximum anisotropy factor (g-factor) of 1.5 * 10(-2) . Shell-driven chiroptical
regulation opens new avenues to feasibly fabricate chiroptically active materials
with desired chiroptical response for the development of switchable recognition
units for sensitive and various target detections.
PMID- 25136977
TI - A CASE OF HAEMATIDROSIS.
PMID- 25136976
TI - Enzymatic degradation of (ligno)cellulose.
AB - Glycoside-degrading enzymes play a dominant role in the biochemical conversion of
cellulosic biomass into low-price biofuels and high-value-added chemicals. New
insight into protein functions and substrate structures, the kinetics of
recognition, and degradation events has resulted in a substantial improvement of
our understanding of cellulose degradation.
PMID- 25136978
TI - The important role of catestatin in cardiac remodeling.
AB - Catestatin (CST) was first discovered as a potent non-competitive and reversible
inhibitor of catecholamine secretion. Recent reports on plasma CST level in heart
diseases suggested a cardioprotective role for this peptide. Given that cardiac
remodeling is the dominant pathologic process in cardiac dysfunction, we propose
that CST participates in the regulation of concern pathways and contributes to
the inhibition of cardiac remodeling. In this minireview, the potential mechanism
of cardiac remodeling involving CST will be discussed from three aspects:
hypertrophy, fibrosis, and apoptosis.
PMID- 25136979
TI - Concordant biogeographic patterns among multiple taxonomic groups in the Mexican
freshwater biota.
AB - In this paper we analyse the degree of concordance in species richness and
taxonomic distinctness (diversity) patterns among different freshwater taxonomic
groups in order to test three long held patterns described in Mexican freshwater
biogeography: 1. The aquatic biota of Mexico includes two distinct faunas, a rich
Neotropical component in the south and a south-eastern region and a less rich
Nearctic component towards central and northern latitudes of the country. 2. A
hotspot of species richness and diversity has been recorded in the Usumacinta,
including the Yucatan Peninsula. 3. The presence of two distinct biotas in
Mexico, an eastern one distributed along the Gulf of Mexico slope, and a western
one associated to the Pacific versant. We use species richness and taxonomic
distinctness to explore patterns of diversity and how these patterns change
between zoogeographical regions. This paper points out a clear separation between
Neotropical and Nearctic drainage basins but also between eastern (Gulf of
Mexico) and western (Pacific) drainage basins. Present data gives additional
empirical support from freshwater biota for three long held beliefs regarding
distributional patterns of the Mexican biota. The neotropical basins of Mexico
are generally host to a richest and more diversified fauna, that includes more
families, genera and species, compared to the less rich and less diverse fauna in
the nearctic basins.
PMID- 25136980
TI - Unveiling the correlation between nanometer-thick molecular monolayer sensitivity
and near-field enhancement and localization in coupled plasmonic oligomers.
AB - Metal nanoclusters, sometimes called metamolecules or plasmonic oligomers,
exhibit interesting optical properties such as Fano resonances and optical
chirality. These properties promise a variety of practical applications,
particularly in ultrasensitive biochemical sensing. Here we investigate
experimentally the sensitivities of plasmonic pentamers and quadrumers to the
adsorption of self-assembled nanometer-thick alkanethiol monolayers. The
monolayer sensitivity of such oligomers is found to be significantly higher than
that of single plasmonic nanoparticles and depends on the nanocluster
arrangement, constituent nanoparticle shape, and the plasmon resonance
wavelength. Together with full-wave numerical simulation results and the
electromagnetic perturbation theory, we unveil a direct correlation between the
sensitivity and the near-field intensity enhancement and spatial localization in
the plasmonic "hot" spots generated in each nanocluster. Our observation is
beyond conventional considerations (such as optimizing nanoparticle geometry or
narrowing resonance line width) for improving the sensing performance of metal
nanoclusters-based biosensors and opens the possibilities of using plasmonic
nanoclusters for single-molecule detection and identification.
PMID- 25136982
TI - Registration of 2D histological sections with 3D micro-CT datasets from small
animal vertebrae and tibiae.
AB - The aim of this study was the registration of digitized thin 2D sections of mouse
vertebrae and tibiae used for histomorphometry of trabecular bone structure into
3D micro computed tomography (MUCT) datasets of the samples from which the
sections were prepared. Intensity-based and segmentation-based registrations
(SegRegs) of 2D sections and 3D MUCT datasets were applied. As the 2D sections
were deformed during their preparation, affine registration for the vertebrae was
used instead of rigid registration. Tibiae sections were additionally cut on the
distal end, which subsequently undergone more deformation so that elastic
registration was necessary. The Jaccard distance was used as registration quality
measure. The quality of intensity-based registrations and SegRegs was practically
equal, although precision errors of the elastic registration of segmentation
masks in tibiae were lower, while those in vertebrae were lower for the intensity
based registration. Results of SegReg significantly depended on the segmentation
of the MUCT datasets. Accuracy errors were reduced from approximately 64% to 42%
when applying affine instead of rigid transformations for the vertebrae and from
about 43% to 24% when using B-spline instead of rigid transformations for the
tibiae. Accuracy errors can also be caused by the difference in spatial
resolution between the thin sections (pixel size: 7.25 MUm) and the MUCT data
(voxel size: 15 MUm). In the vertebrae, average deformations amounted to a 6.7%
shortening along the direction of sectioning and a 4% extension along the
perpendicular direction corresponding to 0.13-0.17 mm. Maximum offsets in the
mouse tibiae were 0.16 mm on average.
PMID- 25136981
TI - Potentially inappropriate medication use in older patients in Swiss managed care
plans: prevalence, determinants and association with hospitalization.
AB - OBJECTIVES: To describe the prevalence and determinants of potentially
inappropriate medication (PIM) use and association with hospitalizations in an
elderly managed care population in Switzerland. METHODS: Using health care claims
data of four health insurers for a sample of managed care patients 65 years of
age and older to compare persons on PIM with persons not on PIM. Beers' 2012 and
PRISCUS criteria were used to determine the potential inappropriateness of
prescribed medications. The sample included 16'490 elderly patients on PIM and
33'178 patients not on PIM in the time period of January 1, 2008 through December
31, 2012. Prevalence estimates are standardized to the population of Switzerland.
Associations between PIM and hospitalizations were examined by multivariate Cox
regression analyses controlling for possible confounding variables. RESULTS: The
estimated prevalence of PIM use in our managed care sample was 22.5%. Logistic
regression analysis showed that number of different medications used in the
previous year, total costs in the previous year and hospitalization in the
previous year all significantly increased the likelihood of receiving PIM.
Multiple Cox regression analysis revealed that those on cumulative levels of PIM
use acted significantly as a factor related to greater hospitalization rates: the
adjusted HR was 1.13 (95% CI 1.07-1.19) for 1 PIM, 1.27 (95% CI 1.19-1.35) for 2
PIM, 1.35 (95% CI 1.22-1.50) for 3 PIM, and 1.63 (95% CI 1.40-1.90) for more than
3 PIM compared to no PIM use. CONCLUSIONS: The prevalence of PIM in managed care
health plans are widely found but seem to be much lower than rates of non-managed
care plans. Furthermore, our study revealed a significant association with
adverse outcomes in terms of hospitalizations. These findings stress the need for
further development of interventions to decrease drug-related problems and manage
patients with multiple chronic conditions.
PMID- 25136983
TI - Influence of organic solvents on catalytic behaviors and cell morphology of whole
cell biocatalysts for synthesis of 5'-arabinocytosine laurate.
AB - A whole-cell based method was developed for the regioselective synthesis of
arabinocytosine laurate. Among the seven kinds of bacteria strains tested in the
acylation reaction, Pseudomonas fluorescens gave the highest productivity and a
higher 5'-regioselectivity than 99%. Compared with pure organic solvents, the use
of organic solvent mixtures greatly promoted the yield of the whole-cell
catalyzed reaction, but showed little influence on the 5'-regioselectivity. Of
all the tested solvent mixtures, the best reaction result was found in isopropyl
ether/pyridine followed by isopentanol/pyridine. However, the whole-cells showed
much lower thermostability in isopropyl ether/pyridine than in THF-pyridine. To
better understand the toxic effects of the organic solvents on P. fluorescens
whole-cells and growing cells were further examined. Significant influences of
organic solvents on the biomass of the cells were found, which differed depending
on the type of solvents used. SEM analysis visually revealed the changes in the
surface morphology of whole-cells and growing cells cultured in media containing
various organic solvents, in terms of surface smoothness, bulges and changed cell
sizes. Results demonstrated that organic toxicity to cell structure played an
important role in whole-cell mediated catalysis.
PMID- 25136985
TI - Sequential inclusion of two berberine cations in cucurbit[8]uril cavity: kinetic
and thermodynamic studies.
AB - A combination of absorption and fluorescence spectroscopic studies with
isothermal calorimetric titrations and stopped-flow measurements is a powerful
way to reveal the thermodynamics and kinetics of inclusion complex formation with
cucurbit[8]uril (CB8). The unique photophysical characteristics of berberine
(B(+)), a pharmaceutically important natural alkaloid, were exploited to
distinguish the consecutive encapsulation processes, and to examine the
confinement in the CB8 cavity. The highly environment sensitive fluorescence
lifetime of B(+) permitted the selective detection of various cucurbituril
complexes, and indicated to what extent the embedded guest was available for
interaction with water. Highly stable 1 : 1 and 2 : 1 B(+) : CB8 complexes were
produced due to the release of the high energy water molecules from the CB8
interior, and the second binding step proved to be almost 3 times more
exothermic. The favorable entropy change contributed appreciably to the driving
force of 1 : 1 encapsulation. In contrast, the embedment of the second B(+) in
CB8 led to substantial entropy diminution. The kinetics of encapsulation was
followed in real time by recording the fluorescence intensity change after rapid
mixing of B(+) and CB8. No evidence was found for intermediates. The rate
constants of (64 +/- 9) * 10(6), and (5.0 +/- 0.5) * 10(6) M(-1) s(-1) were found
for the 1 : 1 and 2 : 1 associations, whereas 3.8 +/- 0.6, and 0.6 +/- 0.1 s(-1)
were obtained as the rate constants of the reverse processes at 283 K,
respectively.
PMID- 25136986
TI - Interface recombination current in type II heterostructure bipolar diodes.
AB - Wide-gap semiconductors are often unipolar and can form type II bipolar
heterostructures with large band discontinuities. We present such diodes with
very high rectification larger than 1 * 10(10). The current is assumed to be
entirely due to interface recombination. We derive the ideality factor for both
symmetric and asymmetric diodes and find it close to 2 in agreement with
experimental data from NiO/ZnO and CuI/ZnO type II diodes. The comparison with
experimental results shows that the actual interface recombination rate is orders
of magnitude smaller than its possible maximum value.
PMID- 25136984
TI - Rhinitis, asthma and respiratory infections among adults in relation to the home
environment in multi-family buildings in Sweden.
AB - Risk factors for rhinitis, asthma and respiratory infections in the home
environment were studied by a questionnaire survey. Totally 5775 occupants (>= 18
years old) from a stratified random sample of multi-family buildings in Sweden
participated (46%). 51.0% had rhinitis in the last 3 months (current rhinitis);
11.5% doctor diagnosed asthma; 46.4% respiratory infections in the last 3 months
and 11.9% antibiotic medication for respiratory infections in the last 12 months.
Associations between home environment and health were analyzed by multiple
logistic regression, controlling for gender, age and smoking and mutual
adjustment. Buildings constructed during 1960-1975 were risk factors for day time
breathlessness (OR = 1.53, 95%CI 1.03-2.29). And those constructed during 1976
1985 had more current rhinitis (OR = 1.43, 95%CI 1.12-1.84) and respiratory
infections (OR = 1.46, 95%CI 1.21-1.78). Cities with higher population density
had more current rhinitis (p = 0.008) and respiratory infections (p<0.001).
Rented apartments had more current rhinitis (OR = 1.23, 95%CI 1.07-1.40), wheeze
(OR = 1.20, 95%CI 1.02-1.41), day time breathlessness (OR = 1.31, 95%CI 1.04
1.66) and respiratory infections (OR = 1.13, 95%CI 1.01-1.26). Living in colder
parts of the country was a risk factor for wheeze (p = 0.03) and night time
breathlessness (p = 0.002). Building dampness was a risk factor for wheeze (OR =
1.42, 95%CI 1.08-1.86) and day time breathlessness (OR = 1.57, 95%CI 1.09-2.27).
Building dampness was a risk factor for health among those below 66 years old.
Odor at home was a risk factor for doctor diagnosed asthma (OR = 1.49, 95%CI 1.08
2.06) and current asthma (OR = 1.52, 95%CI 1.03-2.24). Environmental tobacco
smoke (ETS) was a risk factor for current asthma (OR = 1.53, 95%CI 1.09-2.16).
Window panel condensation was a risk factor for antibiotic medication for
respiratory infections (OR = 1.41, 95%CI 1.10-1.82). In conclusion, rhinitis,
asthma and respiratory infections were related to a number of factors in the home
environment. Certain building years (1961-1985), building dampness, window panel
condensation and odor in the dwelling may be risk factors.
PMID- 25136987
TI - The potential impact of a 20% tax on sugar-sweetened beverages on obesity in
South African adults: a mathematical model.
AB - BACKGROUND/OBJECTIVES: The prevalence of obesity in South Africa has risen
sharply, as has the consumption of sugar-sweetened beverages (SSBs). Research
shows that consumption of SSBs leads to weight gain in both adults and children,
and reducing SSBs will significantly impact the prevalence of obesity and its
related diseases. We estimated the effect of a 20% tax on SSBs on the prevalence
of and obesity among adults in South Africa. METHODS: A mathematical simulation
model was constructed to estimate the effect of a 20% SSB tax on the prevalence
of obesity. We used consumption data from the 2012 SA National Health and
Nutrition Examination Survey and a previous meta-analysis of studies on own- and
cross-price elasticities of SSBs to estimate the shift in daily energy
consumption expected of increased prices of SSBs, and energy balance equations to
estimate shifts in body mass index. The population distribution of BMI by age and
sex was modelled by fitting measured data from the SA National Income Dynamics
Survey 2012 to the lognormal distribution and shifting the mean values.
Uncertainty was assessed with Monte Carlo simulations. RESULTS: A 20% tax is
predicted to reduce energy intake by about 36 kJ per day (95% CI: 9-68 kJ).
Obesity is projected to reduce by 3.8% (95% CI: 0.6%-7.1%) in men and 2.4% (95%
CI: 0.4%-4.4%) in women. The number of obese adults would decrease by over 220
000 (95% CI: 24 197-411 759). CONCLUSIONS: Taxing SSBs could impact the burden of
obesity in South Africa particularly in young adults, as one component of a multi
faceted effort to prevent obesity.
PMID- 25136989
TI - Non-injection synthesis of doped zinc oxide plasmonic nanocrystals.
AB - Plasmonic metal oxide nanocrystals bridge the optoelectronic gap between
semiconductors and metals. In this study, we report a facile, non-injection
synthesis of ZnO nanocrystals doped with Al, Ga, or In. The reaction readily
permits dopant/zinc atomic ratios of over 15%, is amenable to high precursor
concentrations (0.2 M and greater), and provides high reaction yields (>90%). The
resulting colloidal dispersions exhibit high transparency in the visible spectrum
and a wavelength-tunable infrared absorption, which arises from a dopant-induced
surface plasmon resonance. Through a detailed investigation of reaction
parameters, the reaction mechanism is fully characterized and correlated to the
optical properties of the synthesized nanocrystals. The distinctive optical
features of these doped nanocrystals are shown to be readily harnessed within
thin films that are suitable for optoelectronic applications.
PMID- 25136990
TI - Milling, water uptake, and modification properties of different barley (Hordeum
vulgare L.) lots in relation to grain composition and structure.
AB - Milling properties, water uptake, and modification in malting were studied in 14
barley (Hordeum vulgare L.) lots from two consecutive crop years. In all barley
lots studied, grains with lower beta-glucan and protein content and higher starch
content produced finer flours upon milling. Grains with lower beta-glucan content
also hydrated more rapidly during steeping. A detailed study of two cultivars
from two crop years indicated that similar environmental conditions could induce
a higher beta-glucan content and concentration of aggregated B hordein in the
peripheral endosperm and a lower proportion of C hordein entrapped among
aggregated hordeins deeper within the endosperm. These characteristics were
associated with production of coarser flours during milling as well as with
slower water uptake and lower modification. However, the data do not distinguish
between the effect of beta-glucan content and that of hordein localization.
Distribution of beta-glucan or total protein within the kernel was not linked to
hydration or modification.
PMID- 25136988
TI - High IL-17E and low IL-17C dermal expression identifies a fibrosis-specific motif
common to morphea and systemic sclerosis.
AB - BACKGROUND: High interleukin (IL)-17A levels are characteristically found in the
skin of systemic sclerosis (SSc) individuals. Our aim was to investigate whether
the dermal expression of IL-17A and related IL-17 family members (i.e. IL-17C, IL
17E and IL-17F) could distinguish fibrotic from healthy skin and could show
similarities in SSc and morphea, two disorders with presumed distinct
pathogenesis, but characterized by skin fibrosis. METHODS: Biopsies were obtained
from the involved skin of 14 SSc, 5 morphea and 8 healthy donors (HD) undergoing
plastic surgery. Immunohistochemistry/immunofluorescence techniques were coupled
to a semi-automated imaging quantification approach to determine the presence of
the IL-17 family members in the skin. The in vitro effects induced by the IL-17
family members on fibroblasts from normal and SSc individuals were assessed by
ELISA and RIA. RESULTS: Positive cells for each of the IL-17 isoforms
investigated were present in the dermis of all the individuals tested, though
with variable frequencies. SSc individuals had increased frequency of IL-17A+ (p
= 0.0237) and decreased frequency of IL-17F+ (p = 0.0127) and IL-17C+ cells (p =
0.0008) when compared to HD. Similarly, morphea individuals had less frequent IL
17C+ cells (p = 0.0186) in their skin but showed similar number of IL-17A+ and IL
17F+ cells when compared to HD. Finally, IL-17E+ cells were more numerous in
morphea (p = 0.0109) and tended to be more frequent in SSc than in HD. Fibroblast
production of IL-6, MMP-1 and MCP-1 was enhanced in a dose-dependent manner in
the presence of IL-17E and IL-17F, but not in the presence of IL-17C. None of the
cytokine tested had significant effect on type I collagen production. Of
interest, in SSc the frequency of both IL-17A and IL-17F positive cells increased
with disease duration. CONCLUSIONS: The frequency of IL-17A and IL-17F
distinguish SSc to morphea individuals while dermal expression of IL-17C (low)
and IL-17E (high) identifies a fibrosis-specific motif. The specific IL-17C/IL
17E cytokine combination may thus play a role in the development of fibrosis.
PMID- 25136991
TI - Visible light-driven pure water splitting by a nature-inspired organic
semiconductor-based system.
AB - For the first time, it is demonstrated that the robust organic semiconductor g
C3N4 can be integrated into a nature-inspired water splitting system, analogous
to PSII and PSI in natural photosynthesis. Two parallel systems have been
developed for overall water splitting under visible light involving graphitic
carbon nitride with two different metal oxides, BiVO4 and WO3. Consequently, both
hydrogen and oxygen can be evolved in an ideal ratio of 2:1, and evolution rates
in both systems have been found to be dependent on pH, redox mediator
concentration, and mass ratio between the two photocatalysts, leading to a stable
and reproducible H2 and O2 evolution rate at 36 and 18 MUmol h(-1) g(-1) from
water over 14 h. Our findings demonstrate g-C3N4 can serve as a multifunctional
robust photocatalyst, which could also be used in other systems such as PEC cells
or coupled solar cell systems.
PMID- 25136992
TI - Magnetic coupling and slow relaxation of magnetization in chain-based Mn(II),
Co(II), and Ni(II) coordination frameworks.
AB - Three isomorphous coordination polymers based on the chain with triple (MU-1,1
N3)(MU-1,3-COO)2 bridges have been synthesized from a new zwitterionic
dicarboxylate ligand [L(-) = 1-(4-carboxylatobenzyl)pyridinium-4-carboxylate].
They are of formula [M(L)(N3)]n.3nH2O [M = Mn(II), Co(II), and Ni(II)]. In these
compounds, the mixed-bridge chains are linked into 2D coordination networks by
the N-benzylpyridinium spacers. The magnetic properties depend strongly on the
nature of the metal center. The magnetic coupling through (MU-1,1-N3)(MU-1,3
COO)2 is antiferromagnetic in the Mn(II) compound but ferromagnetic in the Co(II)
and Ni(II) analogues. Magnetostructural analyses indicate that the magnitude of
the magnetic coupling can be correlated to the M-N-M angle of the azide bridge
and the average M-O-C-O torsion angle of the carboxylate bridge. As the values of
these parameters increase, the antiferromagnetic coupling for Mn(II) decreases
while the ferromagnetic coupling for Co(II) increases. With strong magnetic
anisotropy, the Co(II) compound behaves as a single-chain magnet showing
hysteresis and Glauber-type slow dynamics probably in the infinite-chain region,
with Delta(tau)/k = 86 K, Delta(xi)/k = 26 K, and Delta(A)/k = 34 K. With weaker
anisotropy, the Ni(II) species shows slow relaxation of magnetization at much
lower temperature.
PMID- 25136993
TI - Do neuraxial techniques affect perioperative outcomes? The story of vantage
points and number games.
PMID- 25136994
TI - Vitamin D and your patients: don't accept wimpy.
PMID- 25136995
TI - The growing burden of perioperative heart failure.
PMID- 25136996
TI - Hydroxyethyl starches: a tale of two contexts: the problem of knowledge.
PMID- 25136997
TI - Cognitive outcomes after infant spinal anesthesia: the other side of the coin.
PMID- 25136998
TI - Goal-directed therapy: time to move on?
PMID- 25136999
TI - Hypovitaminosis D in hospitalized patients: a marker of frailty or a disease
requiring treatment?
PMID- 25137000
TI - Positive end-expiratory pressure to increase internal jugular vein size is poorly
tolerated in obese anesthetized adults.
AB - BACKGROUND: Central venous cannulation is technically challenging in obese
patients. We hypothesized that positive end-expiratory pressure (PEEP) increases
the size of the internal jugular vein (IJV) in obese adults. METHODS: The
circumference and cross-sectional area of the IJV were measured in obese patients
under general anesthesia at PEEP 0, 5, and 10 cm H2O. Results are reported as
means +/- SE. RESULTS: PEEP at 10 cm H2O was tolerated by 18 of 24 obese
patients. Each 5 cm H2O of PEEP increased the cross-sectional area by 0.16 +/-
0.02 cm (P < 0.0001) and the circumference by 0.23 +/- 0.03 cm (P < 0.0001).
CONCLUSIONS: PEEP modestly increases the size of the IJV in obese adults but was
poorly tolerated because of hypotension.
PMID- 25137001
TI - Neurodevelopmental assessment after anesthesia in childhood: review of the
literature and recommendations.
AB - Preclinical studies have established that anesthesia is toxic to the brain in
neonatal animals, but scant research investigates the neurodevelopmental effects
of exposure to anesthesia. In this article, we discuss the issue of outcome
measurement of children after anesthesia administered between infancy and
approximately 4 years of age. Recent studies are reviewed with the goal of
understanding the contributions and limitations of the extant literature with
respect to neurodevelopmental outcome. A review of school-based information
(academic achievement and learning disability characterization), which are most
frequently applied to measure cognitive outcome in cohort studies, is provided.
The strengths and limitations of this literature is reviewed, followed by a
discussion of how future trials investigating neurodevelopmental outcome after
anesthesia might be improved by procedures designed specifically to assess the
status of the central nervous system. Neuropsychological assessment is described
and proposed as a way to increase the validity and sensitivity of forthcoming
studies that intend to evaluate the short- and long-term effects of exposure to
anesthesia during infancy and early childhood.
PMID- 25137002
TI - Bernoulli Cumulative Sum (CUSUM) control charts for monitoring of
anesthesiologists' performance in supervising anesthesia residents and nurse
anesthetists.
AB - We describe our experiences in using Bernoulli cumulative sum (CUSUM) control
charts for monitoring clinician performance. The supervision provided by each
anesthesiologist is evaluated daily by the Certified Registered Nurse
Anesthetists (CRNAs) and/or anesthesia residents with whom they work. Each of 9
items is evaluated (1 = never, 2 = rarely, 3 = frequently, 4 = always). The score
is the mean of the 9 responses. Choosing thresholds for low scores is
straightforward, <2.0 for CRNAs and <3.0 for residents. Bernoulli CUSUM detection
of low scores was within 50 +/- 14 (median +/- quartile deviation) days rather
than 182 days without use of CUSUM. The true positive detection of
anesthesiologists with incidences of low scores greater than the chosen "out-of
control" rate was 14 of 14. The false-positive detection rate was 0 of 29. This
CUSUM performance exceeded that of Shewhart individual control charts, for which
the smallest threshold sufficiently large to detect 14 of 14 true positives had
false-positive detection of 16 of 29 anesthesiologists. The Bernoulli CUSUM
assumes that scores are known right away, which is untrue. However, CUSUM
performance was insensitive to this assumption. The Bernoulli CUSUM assumes
statistical independence of scores, which also is untrue. For example, when an
evaluation of an anesthesiologist 1 day by a CRNA had a low score, there was an
increased chance that another CRNA working in a different operating room on the
same day would also give that same anesthesiologist a low score (P < 0.0001).
This correlation among scores does affect the Bernoulli CUSUM, such that
detection is more likely. This is an advantage for our continual process
improvement application since it flags individuals for further evaluation by
managers while maintaining confidentiality of raters.
PMID- 25137004
TI - Intravenous starches: is suspension the best solution?
PMID- 25137003
TI - Interleukin 10 mediated by herpes simplex virus vectors suppresses neuropathic
pain induced by human immunodeficiency virus gp120 in rats.
AB - BACKGROUND: Human immunodeficiency virus (HIV)-associated sensory neuropathy is a
common neurological complication of HIV infection affecting up to 30% of HIV
positive individuals. However, the exact neuropathological mechanisms remain
unknown, which hinders our ability to develop effective treatments for HIV
related neuropathic pain (NP). In this study, we tested the hypothesis that
inhibition of proinflammatory factors with overexpression of interleukin (IL)-10
reduces HIV-related NP in a rat model. METHODS: NP was induced by the application
of recombinant HIV-1 envelope protein gp120 into the sciatic nerve. The hindpaws
of rats were inoculated with nonreplicating herpes simplex virus (HSV) vectors
expressing anti-inflammatory cytokine IL-10 or control vector. Mechanical
threshold was tested using von Frey filaments before and after treatments with
the vectors. The mechanical threshold response was assessed over time using the
area under curves. The expression of phosphorylated p38 mitogen-activated kinase,
tumor necrosis factor-alpha, stromal cell-derived factor-1alpha, and C-X-C
chemokine receptor type 4 in both the lumbar spinal cord and the L4/5 dorsal root
ganglia (DRG), was examined at 14 and 28 days after vector inoculation using
Western blots. RESULTS: We found that in the gp120-induced NP model, IL-10
overexpression mediated by the HSV vector resulted in a significant elevation of
the mechanical threshold that was apparent on day 3 after vector inoculation
compared with the control vector (P < 0.001). The antiallodynic effect of the
single HSV vector inoculation expressing IL-10 lasted >28 days. The area under
curve in the HSV vector expressing IL-10 was increased compared with that in the
control vector (P < 0.0001). HSV vectors expressing IL-10 reversed the
upregulation of phosphorylated p38 mitogen-activated kinase, tumor necrosis
factor-alpha, stromal cell-derived factor-1alpha, and C-X-C chemokine receptor
type 4 expression at 14 and/or 28 days in the DRG and/or the spinal dorsal horn.
CONCLUSIONS: Our studies demonstrate that blocking the signaling of these
proinflammatory molecules in the DRG and/or the spinal cord using the HSV vector
expressing IL-10 is able to reduce HIV-related NP. These results provide new
insights on the potential mechanisms of HIV-associated NP and a proof of concept
for treating painful HIV sensory neuropathy with this type of gene therapy.
PMID- 25137005
TI - Volume therapy with hydroxyethyl starches: are we throwing the anesthesia baby
out with the intensive care unit bathwater?
PMID- 25137006
TI - Does regional analgesia for major surgery improve outcome? Focus on epidural
analgesia.
PMID- 25137007
TI - Does it expire, or doesn't it? Only the manufacturer knows for sure.
PMID- 25137008
TI - Plagiarism by any other name (author)?
PMID- 25137009
TI - Textbook plagiarism reform.
PMID- 25137010
TI - Why is there still plagiarism?
PMID- 25137011
TI - In response.
PMID- 25137012
TI - Improved quality of anesthesia and cancer recurrence studies.
PMID- 25137013
TI - Small-molecule inhibitors of SETD8 with cellular activity.
AB - SETD8/SET8/Pr-SET7/KMT5A is the sole protein lysine methyltransferase (PKMT)
known to monomethylate lysine 20 of histone H4 in vivo. SETD8's methyltransferase
activity has been implicated in many essential cellular processes including DNA
replication, DNA damage response, transcription modulation, and cell cycle
regulation. Developing SETD8 inhibitors with cellular activity is a key step
toward elucidating the diverse roles of SETD8 via convenient pharmacological
perturbation. From the hits of a prior high throughput screen (HTS), SPS8I1-3
(NSC663284, BVT948, and ryuvidine) were validated as potent SETD8 inhibitors.
These compounds contain different structural motifs and inhibit SETD8 via
distinct modes. More importantly, these compounds show cellular activity by
suppressing the H4K20me1 mark of SETD8 and recapitulate characteristic S/G2/M
phase cell cycle defects as observed for RNAi-mediated SETD8 knockdown. The
commonality of SPS8I1-3 against SETD8, together with their distinct structures
and mechanisms for SETD8 inhibition, argues for the collective application of
these compounds as SETD8 inhibitors.
PMID- 25137014
TI - New glycoproteomics software, GlycoPep Evaluator, generates decoy glycopeptides
de novo and enables accurate false discovery rate analysis for small data sets.
AB - Glycoproteins are biologically significant large molecules that participate in
numerous cellular activities. In order to obtain site-specific protein
glycosylation information, intact glycopeptides, with the glycan attached to the
peptide sequence, are characterized by tandem mass spectrometry (MS/MS) methods
such as collision-induced dissociation (CID) and electron transfer dissociation
(ETD). While several emerging automated tools are developed, no consensus is
present in the field about the best way to determine the reliability of the tools
and/or provide the false discovery rate (FDR). A common approach to calculate
FDRs for glycopeptide analysis, adopted from the target-decoy strategy in
proteomics, employs a decoy database that is created based on the target protein
sequence database. Nonetheless, this approach is not optimal in measuring the
confidence of N-linked glycopeptide matches, because the glycopeptide data set is
considerably smaller compared to that of peptides, and the requirement of a
consensus sequence for N-glycosylation further limits the number of possible
decoy glycopeptides tested in a database search. To address the need to
accurately determine FDRs for automated glycopeptide assignments, we developed
GlycoPep Evaluator (GPE), a tool that helps to measure FDRs in identifying
glycopeptides without using a decoy database. GPE generates decoy glycopeptides
de novo for every target glycopeptide, in a 1:20 target-to-decoy ratio. The
decoys, along with target glycopeptides, are scored against the ETD data, from
which FDRs can be calculated accurately based on the number of decoy matches and
the ratio of the number of targets to decoys, for small data sets. GPE is freely
accessible for download and can work with any search engine that interprets ETD
data of N-linked glycopeptides. The software is provided at
https://desairegroup.ku.edu/research.
PMID- 25137016
TI - Recent developments in transition metal-catalysed spiroketalisation.
AB - The spiroketal motif occurs in a wide range of biologically active natural
products and represents a valuable target in medicinal chemistry and total
synthesis. In recent years, innovative new synthetic methods have substantially
expanded the range of potential precursors, cyclisation modes and opportunities
for asymmetric catalysis and tandem processes. This Perspective aims to highlight
recent rapid advances in the use of transition metal catalysis for spiroketal
formation, in the context of our own investigations into gold-catalysed
asymmetric spiroketalisation.
PMID- 25137015
TI - Synthesis of aliphatic sulfur pentafluorides by oxidation of SF5-containing
anisole, phenols, and anilines.
AB - 4-(Pentafluorosulfanyl)catechol, 2-amino-4-(pentafluorosulfanyl)phenol, and 2
amino-5-(pentafluorosulfanyl)phenol undergo oxidation by lead tetraacetate at
ambient temperature leading to dearomatization and the formation of SF5
substituted nitriles and esters of cis,cis-hexa-2,4-dienedioic (muconic) acid in
good yields. 4-(Pentafluorosulfanyl)phenol and 4-(pentafluorosulfanyl)anisole are
oxidized by 30% aqueous hydrogen peroxide in concentrated sulfuric acid to
provide 2-(5-oxo-3-(pentafluorosulfanyl)-2,5-dihydrofuran-2-yl)acetic acid [3
(pentafluorosulfanyl)muconolactone] and small amounts of side products--SF5
containing maleic and succinic acids. The methods presented are the first
examples of the practical synthesis of aliphatic SF5-containing compounds from
readily available aromatic ones.
PMID- 25137017
TI - Key role of dual specificity kinase TTK in proliferation and survival of
pancreatic cancer cells.
AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive
human malignancies with an overall 5-year survival rate of <5%. Despite
significant advances in treatment of the disease during the past decade, the
median survival rate (~6 months) has hardly improved, warranting the need to
identify novel targets for therapeutic approaches. METHODS: Quantitative real
time PCR, western blot analyses and immunohistochemical staining of tissue
microarrays were used to analyse the expression of TTK gene in primary PDAC
tissues and cell lines. To inhibit TTK kinase expression in a variety of
pancreatic cancer cell lines, RNA interference was used. Functional roles of this
kinase in the context of PDAC were studied using cell proliferation, viability
and anchorage-independent growth assays. Western blotting, fluorescence-activated
cell sorting analyses and fluorescence microscopy were used to gain mechanistic
insight into the functional effects. CONCLUSIONS: We show that the dual
specificity kinase TTK (also known as Mps1), is strongly overexpressed in human
PDAC. Functionally, cell proliferation was significantly attenuated following TTK
knockdown, whereas apoptosis and necrosis rates were significantly increased. In
addition, anchorage-independent growth, a hallmark of malignant transformation
and metastatic potential, was strongly impaired in the absence of TTK gene
function. Interestingly, immortalised normal pancreatic hTERT-HPNE cells were not
affected by loss of TTK function. Mechanistically, these effects in cancer cells
were associated with increased formation of micronuclei, suggesting that loss of
TTK function in pancreatic cancer cells results in chromosomal instability and
mitotic catastrophe. Taken together, our data show that TTK function is critical
for growth and proliferation of pancreatic cancer cells, thus establishing this
kinase as an interesting new target for novel therapeutic approaches in combating
this malignancy.
PMID- 25137019
TI - Serum endostatin levels are elevated in colorectal cancer and correlate with
invasion and systemic inflammatory markers.
AB - BACKGROUND: Endostatin, a fragment of collagen XVIII, is an endogenous
angiogenesis inhibitor with anti-tumour functions. However, elevated circulating
endostatin concentrations have been found in several human cancers including
colorectal cancer (CRC). METHODS: Serum endostatin levels were measured by enzyme
linked immunoassay from a series of 143 patients with CRC and from 84 controls,
and correlated with detailed clinicopathological features of CRC, serum leukocyte
differential count and C-reactive protein (CRP) levels. RESULTS: Patients with
CRC had higher serum endostatin levels than the controls (P=0.005), and high
levels associated with age, tumour invasion through the muscularis propria and
poor differentiation, but not with metastases. Endostatin levels showed a
positive correlation with the markers of systemic inflammatory response and a
negative correlation with the densities of tumour-infiltrating mast cells and
dendritic cells. Collagen XVIII was expressed in tumour stroma most strikingly in
blood vessels and capillaries, and in the muscle layer of the bowel wall.
CONCLUSIONS: Elevated endostatin levels in CRC correlate with systemic
inflammation and invasion through the muscularis propria. Increased endostatin
level may be a result of invasion-related cleavage of collagen XVIII expressed in
the bowel wall. The negative correlations between serum endostatin and
intratumoural mast cells and immature dendritic cells may reflect angiogenesis
inhibition by endostatin.
PMID- 25137018
TI - Urinary TIMP-1 and MMP-2 levels detect the presence of pancreatic malignancies.
AB - BACKGROUND: A majority of patients with pancreatic malignancies, including both
pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumours
(pNETs), present with advanced disease due to a lack of specific symptoms and
current diagnostic limitations, making this disease extremely difficult to
detect. Our goal was to determine whether urinary matrix metalloproteases (uMMPs)
and/or their endogenous inhibitors, urinary tissue inhibitor of metalloproteases
(uTIMPs), could be detected in the urine of patients with pancreatic malignancies
and whether they may serve as independent predictors of disease status. METHODS:
Retrospective analyses of urine samples (n=139) from PDAC and pNET patients as
well as age- and sex-matched controls were conducted. Urinary MMP-2 and uTIMP-1
levels were determined using ELISA and zymography. Biomarker expression in tumour
and normal pancreatic tissues was analysed via immunohistochemistry (IHC).
RESULTS: Multivariable logistic regression analyses indicated that, when
controlling for age and sex, uMMP-2 (P<0.0001) and uTIMP-1 (P<0.0001) but not
uMMP-9, were significant independent predictors for distinguishing between PDAC
patients and healthy controls. Our data also indicated that uMMP-2 was an
independent predictor of the presence of pNET. In addition, uTIMP-1 levels could
differentiate the two cancer groups, PDAC and pNET, respectively.
Immunohistochemistry analysis confirmed that MMP-2 and TIMP-1 protein expression
is significantly upregulated in PDAC tissue compared with the normal pancreas.
CONCLUSIONS: Taken together, our results suggest that the detection of uMMP-2 and
uTIMP-1 may have diagnostic value in the detection of pancreatic malignancies and
that uTIMP-1 may be useful in distinguishing between pancreatic adenocarcinoma
and neuroendocrine tumours.
PMID- 25137023
TI - Probing the optical property and electronic structure of TiO2 nanomaterials for
renewable energy applications.
PMID- 25137021
TI - Chromosome 9p deletion in clear cell renal cell carcinoma predicts recurrence and
survival following surgery.
AB - BACKGROUND: Wider clinical applications of 9p status in clear cell renal cell
carcinoma (ccRCC) are limited owing to the lack of validation and consensus for
interphase fluorescent in situ hybridisation (I-FISH) scoring technique. The aim
of this study was to analytically validate the applicability of I-FISH in
assessing 9p deletion in ccRCC and to clinically assess its long-term prognostic
impact following surgical excision of ccRCC. METHODS: Tissue microarrays were
constructed from 108 renal cell carcinoma (RCC) tumour paraffin blocks.
Interphase fluorescent in situ hybridisation analysis was undertaken based on
preset criteria by two independent observers to assess interobserver variability.
9p status in ccRCC tumours was determined and correlated to clinicopathological
variables, recurrence-free survival and disease-specific survival. RESULTS: There
were 80 ccRCCs with valid 9p scoring and a median follow-up of 95 months. Kappa
statistic for interobserver variability was 0.71 (good agreement). 9p deletion
was detected in 44% of ccRCCs. 9p loss was associated with higher stage, larger
tumours, necrosis, microvascular and renal vein invasion, and higher SSIGN
(stage, size, grade and necrosis) score. Patients with 9p-deleted ccRCC were at a
higher risk of recurrence (P=0.008) and RCC-specific mortality (P=0.001). On
multivariate analysis, 9p deletion was an independent predictor of recurrence
(hazard ratio 4.323; P=0.021) and RCC-specific mortality (hazard ratio 4.603;
P=0.007). The predictive accuracy of SSIGN score improved from 87.7% to 93.1% by
integrating 9p status to the model (P=0.001). CONCLUSIONS: Loss of 9p is
associated with aggressive ccRCC and worse prognosis in patients following
surgery. Our findings independently confirm the findings of previous reports
relying on I-FISH to detect 9p (CDKN2A) deletion.
PMID- 25137020
TI - Phorbol ester stimulates ethanolamine release from the metastatic basal prostate
cancer cell line PC3 but not from prostate epithelial cell lines LNCaP and P4E6.
AB - BACKGROUND: Malignancy alters cellular complex lipid metabolism and membrane
lipid composition and turnover. Here, we investigated whether tumorigenesis in
cancer-derived prostate epithelial cell lines influences protein kinase C-linked
turnover of ethanolamine phosphoglycerides (EtnPGs) and alters the pattern of
ethanolamine (Etn) metabolites released to the medium. METHODS: Prostate
epithelial cell lines P4E6, LNCaP and PC3 were models of prostate cancer (PCa).
PNT2C2 and PNT1A were models of benign prostate epithelia. Cellular EtnPGs were
labelled with [1-(3)H]-Etn hydrochloride. PKC was activated with phorbol ester
(TPA) and inhibited with Ro31-8220 and GF109203X. D609 was used to inhibit PLD
(phospholipase D). [(3)H]-labelled Etn metabolites were resolved by ion-exchange
chromatography. Sodium oleate and mastoparan were tested as activators of PLD2.
Phospholipase D activity was measured by a transphosphatidylation reaction. Cells
were treated with ionomycin to raise intracellular Ca(2+) levels. RESULTS:
Unstimulated cell lines release mainly Etn and glycerylphosphorylEtn (GPEtn) to
the medium. Phorbol ester treatment over 3h increased Etn metabolite release from
the metastatic PC3 cell line and the benign cell lines PNT2C2 and PNT1A but not
from the tumour-derived cell lines P4E6 and LNCaP; this effect was blocked by
Ro31-8220 and GF109203X as well as by D609, which inhibited PLD in a
transphosphatidylation reaction. Only metastatic PC3 cells specifically
upregulated Etn release in response to TPA treatment. Oleate and mastoparan
increased GPEtn release from all cell lines at the expense of Etn. Ionomycin
stimulated GPEtn release from benign PNT2C2 cells but not from cancer-derived
cell lines P4E6 or PC3. Ethanolamine did not stimulate the proliferation of LNCaP
or PC3 cell lines but decreased the uptake of choline (Cho). CONCLUSIONS: Only
the metastatic basal PC3 cell line specifically increased the release of Etn on
TPA treatment most probably by PKC activation of PLD1 and increased turnover of
EtnPGs. The phosphatidic acid formed will maintain a cancer phenotype through the
regulation of mTOR. Ethanolamine released from cells may reduce Cho uptake,
regulating the membrane PtdEtn:PtdCho ratio and influencing the action of PtdEtn
binding proteins such as RKIP and the anti-apoptotic hPEBP4. The work highlights
a difference between LNCaP cells used as a model of androgen-dependent early
stage PCa and androgen-independent PC3 cells used to model later refractory stage
disease.
PMID- 25137024
TI - Ab initio study of potential ultrafast internal conversion routes in oxybenzone,
caffeic acid, and ferulic acid: implications for sunscreens.
AB - Oxybenzone (OB) and ferulic acid (FA) both find use in commercial sunscreens;
caffeic acid (CA) differs from FA by virtue of an -OH group in place of a -OCH3
group on the aromatic ring. We report the results of ab initio calculations
designed to explore the excited state nonradiative relaxation pathways that
provide photostability to these molecules and the photoprotection they offer
toward UV-A and UV-B radiation. In the case of OB, internal conversion (IC) is
deduced to occur on ultrafast time scales, via a barrierless electron-driven H
atom transfer pathway from the S1(1(1)npi*) state to a conical intersection (CI)
with the ground (S0) state potential energy surface (PES). The situation with
respect to CA and FA is somewhat less clear-cut, with low energy CIs identified
by linking excited states to the S0 state following photoexcitation and
subsequent evolution along (i) a ring centered out-of-plane deformation
coordinate, (ii) the E/Z isomerism coordinate and, in the case of CA, (iii) an O
H stretch coordinate. Analogy with catechol suggests that the last of these
processes (if active) would lead to radical formation (and thus potential
phototoxicity), encouraging a suggestion that FA might be superior to CA as a
sunscreen ingredient.
PMID- 25137022
TI - Cost-effectiveness of alternative strategies for integrating MRI into breast
cancer screening for women at high risk.
AB - BACKGROUND: Magnetic resonance imaging (MRI) is recommended for women at high
risk for breast cancer. We evaluated the cost-effectiveness of alternative
screening strategies involving MRI. METHODS: Using a microsimulation model, we
generated life histories under different risk profiles, and assessed the impact
of screening on quality-adjusted life-years, and lifetime costs, both discounted
at 3%. We compared 12 screening strategies combining annual or biennial MRI with
mammography and clinical breast examination (CBE) in intervals of 0.5, 1, or 2
years vs without, and reported incremental cost-effectiveness ratios (ICERs).
RESULTS: Based on an ICER threshold of $100,000/QALY, the most cost-effective
strategy for women at 25% lifetime risk was to stagger MRI and mammography plus
CBE every year from age 30 to 74, yielding ICER $58,400 (compared to biennial MRI
alone). At 50% lifetime risk and with 70% reduction in MRI cost, the recommended
strategy was to stagger MRI and mammography plus CBE every 6 months
(ICER=$84,400). At 75% lifetime risk, the recommended strategy is biennial MRI
combined with mammography plus CBE every 6 months (ICER=$62,800). CONCLUSIONS:
The high costs of MRI and its lower specificity are limiting factors for annual
screening schedule of MRI, except for women at sufficiently high risk.
PMID- 25137025
TI - Somatotropinomas, but not nonfunctioning pituitary adenomas, maintain a
functional apoptotic RET/Pit1/ARF/p53 pathway that is blocked by excess GDNF.
AB - Acromegaly is caused by somatotroph cell adenomas (somatotropinomas [ACROs]),
which secrete GH. Human and rodent somatotroph cells express the RET receptor. In
rodents, when normal somatotrophs are deprived of the RET ligand, GDNF (Glial
Cell Derived Neurotrophic Factor), RET is processed intracellularly to induce
overexpression of Pit1 [Transcription factor (gene : POUF1) essential for
transcription of Pituitary hormones GH, PRL and TSHb], which in turn leads to
p19Arf/p53-dependent apoptosis. Our purpose was to ascertain whether human ACROs
maintain the RET/Pit1/p14ARF/p53/apoptosis pathway, relative to nonfunctioning
pituitary adenomas (NFPAs). Apoptosis in the absence and presence of GDNF was
studied in primary cultures of 8 ACROs and 3 NFPAs. Parallel protein extracts
were analyzed for expression of RET, Pit1, p19Arf, p53, and phospho-Akt. When
GDNF deprived, ACRO cells, but not NFPAs, presented marked level of apoptosis
that was prevented in the presence of GDNF. Apoptosis was accompanied by RET
processing, Pit1 accumulation, and p14ARF and p53 induction. GDNF prevented all
these effects via activation of phospho-AKT. Overexpression of human Pit1 (hPit1)
directly induced p19Arf/p53 and apoptosis in a pituitary cell line. Using in
silico studies, 2 CCAAT/enhancer binding protein alpha (cEBPalpha) consensus
binding sites were found to be 100% conserved in mouse, rat, and hPit1 promoters.
Deletion of 1 cEBPalpha site prevented the RET-induced increase in hPit1 promoter
expression. TaqMan qRT-PCR (real time RT-PCR) for RET, Pit1, Arf, TP53, GDNF,
steroidogenic factor 1, and GH was performed in RNA from whole ACRO and NFPA
tumors. ACRO but not NFPA adenomas express RET and Pit1. GDNF expression in the
tumors was positively correlated with RET and negatively correlated with p53. In
conclusion, ACROs maintain an active RET/Pit1/p14Arf/p53/apoptosis pathway that
is inhibited by GDNF. Disruption of GDNF's survival function might constitute a
new therapeutic route in acromegaly.
PMID- 25137026
TI - Triiodothyronine prevents cardiac ischemia/reperfusion mitochondrial impairment
and cell loss by regulating miR30a/p53 axis.
AB - Mitochondrial dysfunctions critically affect cardiomyocyte survival during
ischemia/reperfusion (I/R) injury. In this scenario p53 activates multiple
signaling pathways that impair cardiac mitochondria and promote cell death. p53
is a validated target of miR-30 whose levels fall under ischemic conditions.
Although triiodothyronine (T3) rescues post-ischemic mitochondrial activity and
cell viability, no data are available on its role in the modulation of p53
signaling in I/R. Here we test the hypothesis that early T3 supplementation in
rats inhibits the post I/R activation of p53 pro-death cascade through the
maintenance of miRNA 30a expression. In our model, T3 infusion improves the
recovery of post-ischemic cardiac performance. At the molecular level, the
beneficial effect of T3 is associated with restored levels of miR-30a expression
in the area at risk (AAR) that correspond to p53 mRNA downregulation. The
concomitant decrease in p53 protein content reduces Bax expression and limits
mitochondrial membrane depolarization resulting in preserved mitochondrial
function and decreased apoptosis and necrosis extent in the AAR. Also in primary
cardiomyocyte culture of neonatal rats, T3 prevents both miR-30a downregulation
and p53 raise induced by hypoxia. The regulatory effect of T3 is greatly
suppressed by miR-30a knockdown. Overall these data suggest a new mechanism of T3
mediated cardioprotection that is targeted to mitochondria and acts, at least in
part, through the regulation of miR-30a/p53 axis.
PMID- 25137028
TI - Progesterone induces RhoA Inactivation in male rat aortic smooth muscle cells
through up-regulation of p27(kip1.).
AB - Previously, we showed that progesterone (P4) at physiologic concentrations (5nM
500nM) inhibits proliferation and migration of rat aortic smooth muscle cells
(RASMCs). The P4-induced migration inhibition in RASMC was resulted from Rat
sacroma homolog gene family, member A (RhoA) inactivation induced by activating
the cSrc/AKT/ERK 2/p38 mitogen-activated protein kinase-mediated signaling
pathway. We also demonstrated that up-regulation of cyclin-dependent kinase
inhibitor 1B (p27(kip1)) is involved in the P4-induced migration inhibition in
RASMC. Because P4 can increase formation of the p27(kip1)-RhoA complex in RASMC,
this finding led us to hypothesize that the P4-induced inactivation in RhoA might
be caused by up-regulation of p27(kip1). Here, we showed that P4 increased
phosphorylation of p27(kip1) at Ser10 in the nucleus, which in turn caused
p27(kip1) translocation from the nucleus to the cytosol, subsequently increasing
formation of the p27(kip1)-RhoA complex. These effects were blocked by knocking
down kinase-interacting stathmin (KIS) using KIS small interfering RNA. Knock
down of p27(kip1) abolished the P4-induced decreases in the level of RhoA protein
in RASMC. However, pretreatment of RASMC with the proteasome inhibitor, N
(benzyloxycarbonyl)leucinylleucinylleucinal (MG132), prevented the P4-induced
degradation of p27(kip1) and RhoA. Taken together, our investigation of P4
induced migration inhibition in RASMC showed a sequence of associated
intracellular events that included 1) increase in formation of the KIS-p27(kip1)
complex in the nucleus; 2) phosphorylated nuclear p27(kip1) at Ser10; 3)
increased cytosolic translocation of p27(kip1) and formation of the p27(kip1)
RhoA complex in the cytosol; and 4) degradation of p27(kip1) and RhoA through the
ubiquitin-proteasome pathway. These findings highlight the molecular mechanisms
underlying P4-induced migration inhibition in RASMC.
PMID- 25137027
TI - Role of melanocortin signaling in neuroendocrine and metabolic actions of leptin
in male rats with uncontrolled diabetes.
AB - Although the antidiabetic effects of leptin require intact neuronal melanocortin
signaling in rodents with uncontrolled diabetes (uDM), increased melanocortin
signaling is not sufficient to mimic leptin's glucose-lowering effects. The
current studies were undertaken to clarify the role of melanocortin signaling in
leptin's ability to correct metabolic and neuroendocrine disturbances associated
with uDM. To accomplish this, bilateral cannulae were implanted in the lateral
ventricle of rats with streptozotocin-induced diabetes, and leptin was coinfused
with varying doses of the melanocortin 3/4 receptor (MC3/4R) antagonist, SHU9119.
An additional cohort of streptozotocin-induced diabetes rats received
intracerebroventricular administration of either the MC3/4R agonist, melanotan
II, or its vehicle. Consistent with previous findings, leptin's glucose-lowering
effects were blocked by intracerebroventricular SHU9119. In contrast, leptin
mediated suppression of hyperglucagonemia involves both melanocortin dependent
and independent mechanisms, and the degree of glucagon inhibition was associated
with reduced plasma ketone body levels. Increased central nervous system
melanocortin signaling alone fails to mimic leptin's ability to correct any of
the metabolic or neuroendocrine disturbances associated with uDM. Moreover, the
inability of increased melanocortin signaling to lower diabetic hyperglycemia
does not appear to be secondary to release of the endogenous MC3/4R inverse
agonist, Agouti-related peptide (AgRP), because AgRP knockout mice did not show
increased susceptibility to the antidiabetic effects of increased MC3/4R
signaling. Overall, these data suggest that 1) AgRP is not a major driver of
diabetic hyperglycemia, 2) mechanisms independent of melanocortin signaling
contribute to leptin's antidiabetic effects, and 3) melanocortin receptor
blockade dissociates leptin's glucose-lowering effect from its action on other
features of uDM, including reversal of hyperglucagonemia and ketosis, suggesting
that brain control of ketosis, but not blood glucose levels, is glucagon
dependent.
PMID- 25137030
TI - Calculating hominin and nonhuman anthropoid femoral head diameter from acetabular
size.
AB - Femoral head size provides important information on body size in extinct species.
Although it is well-known that femoral head size is correlated with acetabular
size, the precision with which femoral head size can be estimated from acetabular
size has not been quantified. The availability of accurate 3D surface models of
fossil acetabular remains opens the possibility of obtaining accurate estimates
of femoral head size from even fragmentary fossil remains [Hammond et al.,: Am J
Phys Anthropol 150 (2013) 565-578]. Here we evaluate the relationship between
spheres fit to surface models of the femoral head and acetabulum of a large
sample of extant anthropoid primates. Sphere diameters are tightly correlated and
scale isometrically. In spite of significant taxonomic and possibly functional
differences in the relationship between femoral head size and acetabulum size,
percent prediction errors of estimated femoral head size remain low regardless of
the taxonomic composition of the reference sample. We provide estimates of
femoral head size for a series of fossil hominins and monkeys.
PMID- 25137029
TI - In vivo fluorescence imaging and urinary monoamines as surrogate biomarkers of
disease progression in a mouse model of pheochromocytoma.
AB - Pheochromocytoma (PHEO) is a rare but potentially lethal neuroendocrine tumor
arising from catecholamine-producing chromaffin cells. Especially for metastatic
PHEO, the availability of animal models is essential for developing novel
therapies. For evaluating therapeutic outcome in rodent PHEO models, reliable
quantification of multiple organ lesions depends on dedicated small-animal in
vivo imaging, which is still challenging and only available at specialized
research facilities. Here, we investigated whether whole-body fluorescence
imaging and monitoring of urinary free monoamines provide suitable parameters for
measuring tumor progression in a murine allograft model of PHEO. We generated an
mCherry-expressing mouse PHEO cell line by lentiviral gene transfer. These cells
were injected subcutaneously into nude mice to perform whole-body fluorescence
imaging of tumor development. Urinary free monoamines were measured by liquid
chromatography with tandem mass spectrometry. Tumor fluorescence intensity and
urinary outputs of monoamines showed tumor growth-dependent increases (P < .001)
over the 30 days of monitoring post-tumor engraftment. Concomitantly, systolic
blood pressure was increased significantly during tumor growth. Tumor volume
correlated significantly (P < .001) and strongly with tumor fluorescence
intensity (rs = 0.946), and urinary outputs of dopamine (rs = 0.952),
methoxytyramine (rs = 0.947), norepinephrine (rs = 0.756), and normetanephrine
(rs = 0.949). Dopamine and methoxytyramine outputs allowed for detection of
lesions at diameters below 2.3 mm. Our results demonstrate that mouse
pheochromocytoma (MPC)-mCherry cell tumors are functionally similar to human
PHEO. Both tumor fluorescence intensity and urinary outputs of free monoamines
provide precise parameters of tumor progression in this sc mouse model of PHEO.
This animal model will allow for testing new treatment strategies for chromaffin
cell tumors.
PMID- 25137031
TI - Antidiabetic potentials of essential oil extracted from the leaves of Hoslundia
opposita Vahl.
AB - This study was aimed at assessing the potential of essential oil from the leaf of
Hoslundia opposita in the treatment of diabetes. Forty-eight rats (Rattus
norvegicus) were randomized into two groups; nondiabetic and diabetic groups,
each with four subgroups. Animals in the diabetic group were induced with
diabetes using a single dose of alloxan monohydrate, 160 mg/kg body weight (b.
wt.). The rats were treated with 110 and 220 mg/kg b. wt. of the essential oil.
All treatments were administered, intraperitoneally, once a day for 4 days. In
the nondiabetic condition, there was no effect of the oil on fasting blood
glucose (FBG) levels in rats. In diabetic rats, the oil caused a significant
reduction in FBG levels. Treatment with 110 mg/kg b. wt. of the oil reduced FBG
almost to the normoglycemic level by day 4 and the overall glucose excursion
during a 3-h intraperitoneal glucose tolerance test approached the baseline level
at 120 min. Also, hepatic glycogen was significantly higher, while the glucose
concentrations were lower in the diabetic-treated group when compared with the
diabetic untreated group. Histological examinations revealed a mildly distorted
architecture of the pancreatic islets beta-cells of diabetic rats treated with
the oil, while those of the untreated rats were severely degenerated. Overall,
the in vivo antihyperglycemic activity of the essential oil may prove to be of
clinical importance in the management of type 2 diabetes.
PMID- 25137032
TI - Multicomponent diffusion in solute-containing micelle and microemulsion
solutions.
AB - Holographic interferometry was used to obtain new results for the four
coefficients that determine rates of multicomponent diffusion of hydrophobic
solutes and surfactants in microemulsions. The three solutes pentanol, octanol,
and heptane were examined in microemulsions formed from decaethylene glycol
monododecyl ether (C12E10) and sodium dodecyl sulfate (SDS). These coefficients
are compared with relevant binary and effective binary diffusion coefficients,
and also with ternary diffusion coefficients reported in the literature. It is
shown that a strong coupling exists between the diffusion of hydrophobic solutes
and surfactant in solute-containing microemulsions. In particular, the presence
of a gradient in the concentration of the solute can induce a surprisingly large
flux of surfactant either up or down the solute gradient. Within the framework of
irreversible thermodynamics, these results indicate that hydrophobic solute
molecules significantly alter the chemical potential of the surfactant in
microemulsions. These effects are present to a comparable degree for both the
nonionic C12E10 and ionic SDS microemulsions.
PMID- 25137036
TI - Effect of resveratrol administration on metabolic syndrome, insulin sensitivity,
and insulin secretion.
AB - AIM: This study evaluated the effect of resveratrol administration on metabolic
syndrome, insulin sensitivity, and insulin secretion. METHODS: A randomized,
double-blind, placebo-controlled clinical trial was carried out in 24 patients
with diagnosis of metabolic syndrome in accordance with the International
Diabetes Federation criteria. Glucose and insulin levels were measured after a 75
gram dextrose load. Triglycerides and high-density lipoprotein cholesterol
concentrations at baseline were also evaluated. Twelve patients received trans
resveratrol (500 mg) three times per day before meals for 90 days. The remaining
12 patients received placebo at the same dose. The area under the curve (AUC)
values of glucose and insulin, total insulin secretion, first-phase of insulin
secretion, and insulin sensitivity were calculated. RESULTS: After resveratrol
administration, there were significant differences in total weight (94.4+/-13.2
vs. 90.5+/-12.3 kg, P=0.007), body mass index (BMI) (35.6+/-3.2 vs. 34.3+/-3.0
kg/m(2), P=0.006), fat mass (41.2+/-7.9 vs. 38.8+/-6.0 kg, P=0.001), and waist
circumference (WC) (109+/-9 vs. 105+/-10 cm, P=0.004). There were also
significant differences in AUC of insulin (48,418+/-22,707 vs. 26,473+/-8,273
pmol/L, P=0.003) and insulinogenic index (0.48+/-0.22 vs. 0.28+/-0.08, P=0.004).
CONCLUSIONS: Administration of resveratrol significantly decreases weight, BMI,
fat mass, WC, AUC of insulin, and total insulin secretion.
PMID- 25137033
TI - Recognition and management of delirium among doctors, nurses, physiotherapists,
and psychologists: an Italian survey.
AB - BACKGROUND: There are no studies that have identified the ability to recognize
and manage delirium among Italian health providers caring for patients at risk.
Therefore, the Italian Association of Psychogeriatrics (AIP) conducted a
multicenter survey among doctors, nurses, psychologists and physiotherapists to
assess their competence regarding the theme of delirium and its management in the
everyday clinical practice. METHODS: The survey period was 1st June 2013 to 30th
November 2013. The invitation to participate was sent via email, with publication
on the AIP website. The survey included 14 questions and two case vignettes.
RESULTS: A total of 648/1,500 responses were collected. Most responders were
doctors (n = 322/800), followed by nurses (n = 225/500), psychologists (n =
51/100), and physiotherapists (n = 30/100). Generally, doctors and psychologists
correctly defined delirium, while nurses and physiotherapists did not. The most
frequently used diagnostic tools were the Confusion Assessment Method (CAM) and
the Diagnostic and Statistical Manual of Mental Disorders-IV. Delirium intensity
was rarely assessed. Hypoactive delirium was generally managed with non
pharmacological approaches, while hyperactive delirium with a combination of non
pharmacological and pharmacological approaches. However, possible causes of
delirium were under-assessed by half of doctors and by the majority of other
professionals. Nurses, psychologists and physiotherapists did not answer the case
vignettes, while doctors identified the correct answer in most cases.
CONCLUSIONS: This is the first Italian survey among health providers caring for
patients at risk of delirium. This is also the first survey including doctors,
nurses, psychologists and physiotherapists. The results emphasize the importance
of training to improve knowledge of this relevant unmet medical need.
PMID- 25137035
TI - Evidence for the presence of novel beta-melatonin receptors along with classical
alpha-melatonin receptors in the fish Rasbora daniconius (Ham.).
AB - The effects of melatonin (MT) were examined on the isolated scale melanophores
from dorso-lateral (D-L) and band regions of a tropical fish Rasbora daniconius.
Our study primarily aimed for further depiction of the signaling receptors
involved in MT mediated pigment translocations in the fish. Melanophore Size
Index (MSI) was employed as a recording parameter for the responses of
melanophores to MT and various antagonists. MT has induced aggregation as well as
dispersion in D-L region and aggregation in band region melanophores during
summer season. During winter, MT-induced responses were only of aggregatory type
in D-L region, while in the band region there was an increase in the sensitivity.
The responses of the melanophores to MT were reversible. The aggregation of
innervated melanophores induced by MT on the D-L and band regions was partially
mediated through the neurotransmitters released under the influence of MT and
partially by the specific MT receptors. Luzindole and K185 have completely
blocked the aggregatory responses of D-L and band region melanophores.
Aggregatory receptors may be of the conventional alpha-MT type. Dispersion of D-L
and band region melanophores induced by MT in the presence of various antagonists
and on denervated band region could be the result of activation of beta-MT
receptors of dispersive nature. Presence of alpha and beta MT receptors is thus
indicated in this fish melanophores.
PMID- 25137037
TI - Modulation of chemotherapeutic drug resistance in neuroblastoma SK-N-AS cells by
the neural apoptosis inhibitory protein and miR-520f.
AB - The acquisition of multidrug resistance is a major impediment to the successful
treatment of neuroblastoma, a clinically heterogeneous cancer accounting for ~15%
of all pediatric cancer deaths. The MYCN transcription factor, whose gene is
amplified in ~30% of high-risk neuroblastoma cases, influences drug resistance by
regulating a cadre of genes, including those involved with drug efflux, however,
other high-risk subtypes of neuroblastoma lacking MYCN amplification, such as
those with chromosome 11q deletions, also acquire multidrug resistance. To
elucidate additional mechanisms involved with drug resistance in non-MYCN
amplified tumour cells, an SK-N-AS subline (SK-N-AsCis24) that is significantly
resistant to cisplatin and cross resistant to etoposide was developed through a
pulse-selection process. High resolution aCGH analysis of SK-N-AsCis24 revealed a
focal gain on chromosome 5 containing the coding sequence for the neural
apoptosis inhibitory protein (NAIP). Significant overexpression of NAIP mRNA and
protein was documented, while experimental modulation of NAIP levels in both SK-N
AsCis24 and in parental SK-N-AS cells confirmed that NAIP was responsible for the
drug resistant phenotype by apoptosis inhibition. Furthermore, a decrease in the
NAIP targeting microRNA, miR-520f, was also demonstrated to be partially
responsible for increased NAIP levels in SK-N-AsCis24. Interestingly, miR-520f
levels were determined to be significantly lower in postchemotherapy treatment
tumours relative to matched prechemotherapy samples, consistent with a role for
this miRNA in the acquisition of drug resistance in vivo, potentially through
decreased NAIP targeting. Our findings provide biological novel insight into
neuroblastoma drug-resistance and have implications for future therapeutic
research.
PMID- 25137038
TI - Identification of conserved and novel microRNAs in the Pacific oyster Crassostrea
gigas by deep sequencing.
AB - MicroRNAs (miRNAs) play important roles in regulatory processes in various
organisms. To date many studies have been performed in the investigation of
miRNAs of numerous bilaterians, but limited numbers of miRNAs have been
identified in the few species belonging to the clade Lophotrochozoa. In the
current study, deep sequencing was conducted to identify the miRNAs of
Crassostrea gigas (Lophotrochozoa) at a genomic scale, using 21 libraries that
included different developmental stages and adult organs. A total of 100 hairpin
precursor loci were predicted to encode miRNAs. Of these, 19 precursors (pre
miRNA) were novel in the oyster. As many as 53 (53%) miRNAs were distributed in
clusters and 49 (49%) precursors were intragenic, which suggests two important
biogenetic sources of miRNAs. Different developmental stages were characterized
with specific miRNA expression patterns that highlighted regulatory variation
along a temporal axis. Conserved miRNAs were expressed universally throughout
different stages and organs, whereas novel miRNAs tended to be more specific and
may be related to the determination of the novel body plan. Furthermore, we
developed an index named the miRNA profile age index (miRPAI) to integrate the
evolutionary age and expression levels of miRNAs during a particular
developmental stage. We found that the swimming stages were characterized by the
youngest miRPAIs. Indeed, the large-scale expression of novel miRNAs indicated
the importance of these stages during development, particularly from
organogenetic and evolutionary perspectives. Some potentially important miRNAs
were identified for further study through significant changes between expression
patterns in different developmental events, such as metamorphosis. This study
broadened the knowledge of miRNAs in animals and indicated the presence of
sophisticated miRNA regulatory networks related to the biological processes in
lophotrochozoans.
PMID- 25137039
TI - Enhanced cross-presentation and improved CD8+ T cell responses after
mannosylation of synthetic long peptides in mice.
AB - The use of synthetic long peptides (SLP) has been proven to be a promising
approach to induce adaptive immune responses in vaccination strategies. Here, we
analyzed whether the efficiency to activate cytotoxic T cells by SLP-based
vaccinations can be increased by conjugating SLPs to mannose residues. We could
demonstrate that mannosylation of SLPs results in increased internalization by
the mannose receptor (MR) on murine antigen-presenting cells. MR-mediated
internalization targeted the mannosylated SLPs into early endosomes, from where
they were cross-presented very efficiently compared to non-mannosylated SLPs. The
influence of SLP mannosylation was specific for cross-presentation, as no
influence on MHC II-restricted presentation was observed. Additionally, we showed
that vaccination of mice with mannosylated SLPs containing epitopes from either
ovalbumin or HPV E7 resulted in enhanced proliferation and activation of antigen
specific CD8+ T cells. These findings demonstrate that mannosylation of SLPs
augments the induction of a cytotoxic T cell response in vitro and in vivo and
might be a promising approach to induce cytotoxic T cell responses in e.g. cancer
therapy and anti-viral immunity.
PMID- 25137040
TI - Comparison of interferon-gamma release assay to two cut-off points of tuberculin
skin test to detect latent Mycobacterium tuberculosis infection in primary health
care workers.
AB - BACKGROUND: An interferon-gamma release assay, QuantiFERON-TB (QFT) test, has
been introduced an alternative test for the diagnosis of latent Mycobacterium
tuberculosis infection (LTBI). Here, we compared the performance of QFT with
tuberculin skin test (TST) measured at two different cut-off points among primary
health care work (HCW) in Brazil. METHODS: A cross-sectional study was carried
out among HCWs in four Brazilian cities with a known history of high incidence of
TB. Results of the QFT were compared to TST results based on both >=5 mm and >=10
mm as cut-off points. RESULTS: We enrolled 632 HCWs. When the cut-off value of
>=10 mm was used, agreement between QFT and TST was 69% (k = 0.31), and when the
cut-off of >=5 mm was chosen, the agreement was 57% (k = 0.22). We investigated
possible factors of discordance of TST vs QFT. Compared to the TST-/QFT- group,
risk factors for discordance in the TST+/QFT- group with TST cut-off of >=5 mm
included age between 41-45 years [OR = 2.70; CI 95%: 1.32-5.51] and 46-64 years
[OR = 2.04; CI 95%: 1.05-3.93], BCG scar [OR = 2.72; CI 95%: 1.40-5.25], and
having worked only in primary health care [OR = 2.30; CI 95%: 1.09-4.86]. On the
other hand, for the cut-off of >=10 mm, BCG scar [OR = 2.26; CI 95%: 1.03-4.91],
being a household contact of a TB patient [OR = 1.72; CI 95%: 1.01-2.92] and
having had a previous TST [OR = 1.66; CI 95%: 1.05-2.62], were significantly
associated with the TST+/QFT- group. No statistically significant associations
were found among the TST-/QFT+ discordant group with either TST cut-off value.
CONCLUSIONS: Although we identified BCG vaccination to contribute to the
discordance at both TST cut-off measures, the current Brazilian recommendation
for the initiation of LTBI treatment, based on information gathered from medical
history, TST, chest radiograph and physical examination, should not be changed.
PMID- 25137041
TI - Expression of STAT5, COX-2 and PIAS3 in correlation with NSCLC histhopathological
features.
AB - Signal transducers and activators of transcription (STATs), their inhibitors and
cyclooxygenase-2 (COX-2) participate in transformations of many various types of
cancers. The aim of the present study was to evaluate the relationship between
STAT5A/B, COX-2, and PIAS3 mRNA expression and tumor staging, metastasis status,
and histopathological subtype in 71 patients with confirmed non-small cell lung
cancer (NSCLC) diagnosis. Total RNA was isolated from NSCLC tissue samples and
the expression of the studied genes was assessed using TaqMan probes in real-time
PCR assay. The expression levels of STAT5A, STAT5B, and COX-2 genes were
increased in 69%, 79%, and 71% NSCLC samples respectively, while PIAS3 expression
was decreased in the majority (69%) of the studied tissues. Statistically
significant differences were observed between STAT5 isoforms (P = 0.0008), with
higher expression of STAT5B. We found statistically significant positive
correlation between STAT5B and COX-2 (rho = 0.045), and significant negative
correlation between STAT5B and PIAS3 (rho = -0.049). The negative correlation
between STAT5B and PIAS3 (rho = -0.43) was also observed in T2a+T2b tumor group.
Additionally, STAT5B and COX-2 expression levels were significantly different
between T1a+T1b and T2a+T2b tumors (P = 0.002 and P = 0.041, respectively), with
higher expression of both genes in T2 tumor stage. PIAS3 expression was
significantly lower in NSCC subtype as compared with SCC subtype (P = 0.017).
Also, STAT5A and STAT5B immunoexpression was assessed, and the results indicated
significantly higher protein levels in NSCLC patients as compared with controls
(P = 0.048 and P = 0.034, respectively). High STAT5B immunoexpression was
positively correlated with STAT5B gene expression in tumors (rho = 0.755). STAT5B
protein level was also significantly higher in T2a+T2b tumors, reflecting high
STAT5B gene expression in this group. There was no statistically significant
association between mRNA and protein expression levels of the studied genes and
patients' characteristics: age, gender, smoking. The obtained results highlight
the importance of the genes STAT5B and COX-2 in lung cancer progression.
PMID- 25137042
TI - Oligomerization mechanisms of an H-NS family protein, Pmr, encoded on the plasmid
pCAR1 provide a molecular basis for functions of H-NS family members.
AB - Enterobacterial H-NS-like proteins and Pseudomonas MvaT-like proteins share low
homology at the amino acid sequence level, but both can function as xenogeneic
silencers and are included in the H-NS family of proteins. H-NS family members
have dimerization/oligomerization and DNA-binding domains connected by a flexible
linker and form large nucleoprotein complexes using both domains. Pmr, an MvaT
like protein encoded on the IncP-7 carbazole-degradative plasmid pCAR1, is a key
regulator of an interaction between pCAR1 and its host Pseudomonas putida KT2440.
KT2440 has two transcribed genes that encode the MvaT-like proteins TurA and
TurB. Our previous transcriptome analyses suggested that the functions of Pmr,
TurA and TurB are non-equivalent, although the detailed underlying mechanisms
remain unclear. In this study, we focused on the protein-protein interactions of
Pmr, and assessed the homo-oligomerization capacity of various substituted and
truncated Pmr derivatives by protein-protein cross-linking analysis. Six of the
seven residues identified as important for homo-oligomerization in Pmr were
located near the N-terminus, and the putative flexible linker or the region near
that was not involved in homo-oligomerization, suggesting that Pmr homo
oligomerization is different from that of enterobacterial H-NS and that the
functional mechanism differs between H-NS-like and MvaT-like proteins. In
addition, we assessed homo- and hetero-oligomerization of Pmr by surface plasmon
resonance analysis and found that the coupling ratio of TurB-Pmr oligomers is
smaller than that of Pmr-Pmr or TurA-Pmr oligomers. These results raised the
possibility that composition of the hetero-oligomers of Pmr, TurA, and TurB could
explain why the different gene sets were affected by either pmr, turA, or turB
disruption in our previous studies.
PMID- 25137046
TI - Bugs split to attack and gamble to survive.
PMID- 25137044
TI - Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with
maltose-binding protein elicits humoral and cellular responses.
AB - Glycoconjugate is one of the most efficacious and safest vaccines against
bacterial pathogens. Previous studies of glycoconjugates against pathogen E. coli
O157:H7 focused more on the humoral responses they elicited. However, little was
known about their cellular responses. In this study, we exploited a novel
approach based on bacterial protein N-linked glycosylation system to produce
glycoconjugate containing Escherichia coli O157:H7 O-antigen linked with maltose
binding protein and examined its humoral and cellular responses in BALB/c mice.
The transfer of E. coli O157:H7 O-antigen to MBP was confirmed by western blot
and MALDI-TOF MS. Mice injected with glycoconjugate O-Ag-MBP elicited serum
bactericidal antibodies including anti-E. coli O157:H7 O-antigen IgG and IgM.
Interestingly, O-Ag-MBP also stimulated the secretion of anti-E. coli O157:H7 O
antigen IgA in intestine. In addition, O-Ag-MBP stimulated cellular responses by
recruiting Th1-biased CD4+ T cells, CD8+ T cells. Meanwhile, O-Ag-MBP induced the
upregulation of Th1-related IFN-gamma and downregulation of Th2-related IL-4, and
the upregulation of IFN-gamma was stimulated by MBP in a dose-dependent manner.
MBP showed TLR4 agonist-like properties to activate Th1 cells as carrier protein
of O-Ag-MBP. Thus, glycoconjugate vaccine E. coli O157:H7-specific O-Ag-MBP
produced by bacterial protein N-linked glycosylation system was able to elicit
both humoral and Th1-biased cellular responses.
PMID- 25137043
TI - Molecular signatures of the evolving immune response in mice following a
Bordetella pertussis infection.
AB - Worldwide resurgence of pertussis necessitates the need for improvement of
pertussis vaccines and vaccination strategies. Since natural infections induce a
longer-lasting immunity than vaccinations, detailed knowledge of the immune
responses following natural infection can provide important clues for such
improvement. The purpose was to elucidate the kinetics of the protective immune
response evolving after experimental Bordetella pertussis (B. pertussis)
infection in mice. Data were collected from (i) individual analyses, i.e.
microarray, flow cytometry, multiplex immunoassays, and bacterial clearance; (ii)
twelve time points during the infection; and (iii) different tissues involved in
the immune responses, i.e. lungs, spleen and blood. Combined data revealed
detailed insight in molecular and cellular sequence of events connecting
different phases (innate, bridging and adaptive) of the immune response following
the infection. We detected a prolonged acute phase response, broad pathogen
recognition, and early gene signatures of subsequent T-cell recruitment in the
lungs. Activation of particular transcription factors and specific cell markers
provided insight into the time course of the transition from innate towards
adaptive immune responses, which resulted in a broad spectrum of systemic
antibody subclasses and splenic Th1/Th17 memory cells against B. pertussis. In
addition, signatures preceding the local generation of Th1 and Th17 cells as well
as IgA in the lungs, considered key elements in protection against B. pertussis,
were established. In conclusion, molecular and cellular immunological processes
in response to live B. pertussis infection were unraveled, which may provide
guidance in selecting new vaccine candidates that should evoke local and
prolonged protective immune responses.
PMID- 25137048
TI - Stress tolerance and ecophysiological ability of an invader and a native species
in a seasonally dry tropical forest.
AB - Ecophysiological traits of Prosopis juliflora (Sw.) DC. and a phylogenetically
and ecologically similar native species, Anadenanthera colubrina (Vell.) Brenan,
were studied to understand the invasive species' success in caatinga, a
seasonally dry tropical forest ecosystem of the Brazilian Northeast. To determine
if the invader exhibited a superior resource-capture or a resource-conservative
strategy, we measured biophysical and biochemical parameters in both species
during dry and wet months over the course of two years. The results show that P.
juliflora benefits from a flexible strategy in which it frequently outperforms
the native species in resource capture traits under favorable conditions (e.g.,
photosynthesis), while also showing better stress tolerance (e.g., antioxidant
activity) and water-use efficiency in unfavorable conditions. In addition, across
both seasons the invasive has the advantage over the native with higher
chlorophyll/carotenoids and chlorophyll a/b ratios, percent N, and leaf protein.
We conclude that Prosopis juliflora utilizes light, water and nutrients more
efficiently than Anadenanthera colubrina, and suffers lower intensity oxidative
stress in environments with reduced water availability and high light radiation.
PMID- 25137047
TI - Coupling of X-chromosome reactivation with the pluripotent stem cell state.
AB - X-chromosome inactivation (XCI) in female mammals is a dramatic example of
epigenetic gene regulation, which entails the silencing of an entire chromosome
through a wide range of mechanisms involving noncoding RNAs, chromatin
modifications, and DNA-methylation. While XCI is associated with the
differentiated cell state, it is reversed by X-chromosome reactivation (XCR) ex
vivo in pluripotent stem cells and in vivo in the early mouse embryo and the
germline. Critical in the regulation of XCI vs. XCR is the X-inactivation center,
a multigene locus on the X-chromosome harboring several long noncoding RNA genes
including, most prominently, Xist and Tsix. These genes, which sit at the top of
the XCI hierarchy, are by themselves controlled by pluripotency factors, coupling
XCR with the naive pluripotent stem cell state. In this point-of-view article we
review the latest findings regarding this intricate relationship between cell
differentiation state and epigenetic control of the X-chromosome. In particular,
we discuss the emerging picture of complex multifactorial regulatory mechanisms,
ensuring both a fine-tuned and robust X-reactivation process.
PMID- 25137051
TI - Punishment based on public benefit fund significantly promotes cooperation.
AB - In prisoner's dilemma game (shortly, PD game), punishment is most frequently used
to promote cooperation. However, outcome varies when different punishment
approaches are applied. Here the PD game is studied on a square lattice when
different punishment patterns are adopted. As is known to all, tax system, a
common tool to adjust the temperature of the economy, is widely used in human
society. Inspired by this philosophy, players in this study would pay
corresponding taxes in accordance with their payoff level. In this way, public
benefit fund is established consequently and it would be utilized to punish
defectors. There are two main methods for punishing: slight intensity of
punishment (shortly, SLP) and severe intensity of punishment (shortly, SEP). When
the totaling of public benefit fund keeps relatively fixed, SLP extends further,
which means more defectors would be punished; by contrast, SEP has a smaller
coverage. It is of interest to verify whether these two measures can promote
cooperation and which one is more efficient. Simulate results reveal that both of
them can promote cooperation remarkably. Specifically speaking, SLP shows
constant advantage from the point of view either of fractions of cooperation or
average payoff.
PMID- 25137049
TI - The MacBlue binary transgene (csf1r-gal4VP16/UAS-ECFP) provides a novel marker
for visualisation of subsets of monocytes, macrophages and dendritic cells and
responsiveness to CSF1 administration.
AB - The MacBlue transgenic mouse uses the Csf1r promoter and first intron to drive
expression of gal4-VP16, which in turn drives a cointegrated gal4-responsive UAS
ECFP cassette. The Csf1r promoter region used contains a deletion of a 150 bp
conserved region covering trophoblast and osteoclast-specific transcription start
sites. In this study, we examined expression of the transgene in embryos and
adult mice. In embryos, ECFP was expressed in the large majority of macrophages
derived from the yolk sac, and as the liver became a major site of
monocytopoiesis. In adults, ECFP was detected at high levels in both Ly6C+ and
Ly6C- monocytes and distinguished them from Ly6C+, F4/80+, CSF1R+ immature
myeloid cells in peripheral blood. ECFP was also detected in the large majority
of microglia and Langerhans cells. However, expression was lost from the majority
of tissue macrophages, including Kupffer cells in the liver and F4/80+
macrophages of the lung, kidney, spleen and intestine. The small numbers of
positive cells isolated from the liver resembled blood monocytes. In the gut,
ECFP+ cells were identified primarily as classical dendritic cells or blood
monocytes in disaggregated cell preparations. Immunohistochemistry showed large
numbers of ECFP+ cells in the Peyer's patch and isolated lymphoid follicles. The
MacBlue transgene was used to investigate the effect of treatment with CSF1-Fc, a
form of the growth factor with longer half-life and efficacy. CSF1-Fc massively
expanded both the immature myeloid cell (ECFP-) and Ly6C+ monocyte populations,
but had a smaller effect on Ly6C- monocytes. There were proportional increases in
ECFP+ cells detected in lung and liver, consistent with monocyte infiltration,
but no generation of ECFP+ Kupffer cells. In the gut, there was selective
infiltration of large numbers of cells into the lamina propria and Peyer's
patches. We discuss the use of the MacBlue transgene as a marker of
monocyte/macrophage/dendritic cell differentiation.
PMID- 25137050
TI - Transcriptional response of Musca domestica larvae to bacterial infection.
AB - The house fly Musca domestica, a cosmopolitan dipteran insect, is a significant
vector for human and animal bacterial pathogens, but little is known about its
immune response to these pathogens. To address this issue, we inoculated the
larvae with a mixture of Escherichia coli and Staphylococcus aureus and profiled
the transcriptome 6, 24, and 48 h thereafter. Many genes known to controlling
innate immunity in insects were induced following infection, including genes
encoding pattern recognition proteins (PGRPs), various components of the Toll and
IMD signaling pathways and of the proPO-activating and redox systems, and
multiple antimicrobial peptides. Interestingly, we also uncovered a large set of
novel immune response genes including two broad-spectrum antimicrobial peptides
(muscin and domesticin), which might have evolved to adapt to house-fly's unique
ecological environments. Finally, genes mediating oxidative phosphorylation were
repressed at 48 h post-infection, suggesting disruption of energy homeostasis and
mitochondrial function at the late stages of infection. Collectively, our data
reveal dynamic changes in gene expression following bacterial infection in the
house fly, paving the way for future in-depth analysis of M. domestica's immune
system.
PMID- 25137052
TI - Doxycycline inducible Kruppel-like factor 4 lentiviral vector mediates
mesenchymal to epithelial transition in ovarian cancer cells.
AB - Ovarian cancer presents therapeutic challenges due to its typically late
detection, aggressive metastasis, and therapeutic resistance. The transcription
factor Kruppel-like factor 4 (KLF4) has been implicated in human cancers as a
tumor suppressor or oncogene, although its role depends greatly on the cellular
context. The role of KLF4 in ovarian cancer has not been elucidated in
mechanistic detail. In this study, we investigated the role of KLF4 in ovarian
cancer cells by transducing the ovarian cancer cell lines SKOV3 and OVCAR3 with a
doxycycline-inducible KLF4 lentiviral vector. Overexpression of KLF4 reduced cell
proliferation, migration, and invasion. The epithelial cell marker gene E
cadherin was significantly upregulated, whereas the mesenchymal cell marker genes
vimentin, twist1 and snail2 (slug) were downregulated in both KLF4-expressing
SKOV3 and OVCAR3 cells. KLF4 inhibited the transforming growth factor beta
(TGFbeta)-induced epithelial to mesenchymal transition (EMT) in ovarian cancer
cells. Taken together, our data demonstrate that KLF4 functions as a tumor
suppressor gene in ovarian cancer cells by inhibiting TGFbeta-induced EMT.
PMID- 25137053
TI - Refined candidate region for F4ab/ac enterotoxigenic Escherichia coli
susceptibility situated proximal to MUC13 in pigs.
AB - F4 enterotoxigenic Escherichia coli (F4 ETEC) are an important cause of diarrhea
in neonatal and newly-weaned pigs. Based on the predicted differential O
glycosylation patterns of the 2 MUC13 variants (MUC13A and MUC13B) in F4ac ETEC
susceptible and F4ac ETEC resistant pigs, the MUC13 gene was recently proposed as
the causal gene for F4ac ETEC susceptibility. Because the absence of MUC13 on
Western blot from brush border membrane vesicles of F4ab/acR+ pigs and the
absence of F4ac attachment to immunoprecipitated MUC13 could not support this
hypothesis, a new GWAS study was performed using 52 non-adhesive and 68 strong
adhesive pigs for F4ab/ac ETEC originating from 5 Belgian farms. A refined
candidate region (chr13: 144,810,100-144,993,222) for F4ab/ac ETEC susceptibility
was identified with MUC13 adjacent to the distal part of the region. This
candidate region lacks annotated genes and contains a sequence gap based on the
sequence of the porcine GenomeBuild 10.2. We hypothesize that a porcine orphan
gene or trans-acting element present in the identified candidate region has an
effect on the glycosylation of F4 binding proteins and therefore determines the
F4ab/ac ETEC susceptibility in pigs.
PMID- 25137056
TI - ACUTE INTESTINAL OBSTRUCTION DUE TO INTRA-ABDOMINAL CAUSES.
PMID- 25137054
TI - Identification, localization, and quantification of neuronal cell membrane
receptors with plasmonic probes: role of protein kinase D1 in their distribution.
AB - Detecting, imaging, and being able to localize the distribution of several cell
membrane receptors on a single neuron are very important topics in neuroscience
research. In the present work, the distribution of metabotropic glutamate
receptor 1a (mGluR1a) density on neuron cells on subcellular length scales is
determined by evaluating the role played by protein kinase D1 (PKD1) in the
trafficking of membrane proteins, comparing the distribution of mGluR1a in
experiments performed in endogenous PKD1 expression with those in the presence of
kinase-inactive protein kinase D1 (PKD1-kd). The localization, distribution, and
density of cell surface mGluR1a were evaluated using 90 nm diameter Au
nanoparticle (NP) probes specifically functionalized with a high-affinity and
multivalent labeling function, which allows not only imaging NPs where this
receptor is present but also quantifying by optical means the NP density. This is
so because the NP generates a density (rho)-dependent SERS response that
facilitated a spatial mapping of the mGluR1a density distribution on subcellular
length scales (dendrites and axons) in an optical microscope. The measured rho
values were found to be significantly higher on dendrites than on axons for
endogenous PKD1, while an increase of rho on axons was observed when PKD1 is
altered. The spatial distribution of the NP immunolabels through scanning
electron microscopy (SEM) confirmed the results obtained by fluorescence bright
field analysis and dark-field spectroscopy and provided additional structural
details. In addition, it is shown using electrodynamic simulations that SERS
spectroscopy could be a very sensitive tool for the spatial mapping of cell
membrane receptors on subcellular length scales, as SERS signals are almost
linearly dependent on NP density and therefore give indirect information on the
distribution of cell membrane proteins. This result is important since the
calibration of the rho-dependent near-field enhancement of the Au immunolabels
through correlation of SERS and SEM paves the way toward quantitative
immunolabeling studies of cell membrane proteins involved in neuron polarity.
From the molecular biology point of view, this study shows that in cultured
hippocampal pyramidal cells mGluR1a is predominantly transported to dendrites and
excluded from axons. Expression of kinase-inactive protein kinase D1 (PKD1-kd)
dramatically and selectively alters the intracellular trafficking and membrane
delivery of mGluR1a-containing vesicles.
PMID- 25137058
TI - 3D reconstruction of atomic structures from high angle annular dark field (HAADF)
STEM images and its application on zeolite silicalite-1.
AB - High-resolution transmission electron microscopy (HRTEM) has shown to be very
powerful for solving three-dimensional (3D) structures of unknown crystals. HRTEM
has a unique advantage over diffraction for solving structures. Crystallographic
structure factor phases, which are lost in diffraction can be directly obtained
from HRTEM images. For the determination of a 3D crystalline structure by HRTEM,
the crystallographic structure factor amplitudes and phases extracted from HRTEM
images along different zone axes are combined to reconstruct a 3D electrostatic
potential map. In recent years, scanning transmission electron microscopy (STEM)
has reached the atomic resolution, which is comparable to that of HRTEM. Here we
show, for the first time, that the structure factor phases can be also obtained
from high angle annular dark-field (HAADF)-STEM images and used for 3D
reconstruction of atomic structures. This is applied to the complex zeolite
structure, silicalite-1 (Formula SiO2, framework code MFI, Pnma, a = 20.090 A, b
= 19.738 A and c = 13.142 A). We have compared the amplitudes and phases obtained
from HAADF-STEM images with those from HRTEM images.
PMID- 25137055
TI - Synthesis, PL characterizations and concentration quenching effect in Dy(3+) and
Eu(3+) activated LiCaBO3 phosphor.
AB - LiCaBO3 :Dy(3+) /Eu(3+) phosphors were synthesized by a solid-state reaction. The
synthesized materials were characterized using powder X-ray diffraction pattern
(XRD) for confirmation. All the structural parameters were calculated from the
XRD data. Scanning electron microscopy (SEM) images showed rod-like morphology.
Photoluminescence (PL) emission spectra showed two emissions (484 and 577 nm) in
Dy(3+) -doped LiCaBO3 :Dy(3+) phosphors with the concentration quenching effect
and the critical distance was calculated to be about 22.76 A. LiCaBO3 :Eu(3+)
phosphor was effectively excited by a near-UV light of 392 nm. The emission
spectra exhibited the transition from (5) D0 level to (7) FJ (J = 0-2) with main
emission at 614 nm, which comes from the electrodipole transition because of the
asymmetric point group. The quenching concentration of Eu(3+) is about 0.2 mol%,
and the critical distance was calculated to be about 38.93 A.
PMID- 25137059
TI - Diabetes mellitus as a risk factor for open-angle glaucoma: a systematic review
and meta-analysis.
AB - OBJECTIVE: To determine the association between diabetes mellitus (DM) and
primary open-angle glaucoma (POAG). METHODS: This is a systematic review and meta
analysis of case-control and cohort studies. The literature search included two
databases (PubMed and Embase) and the reference lists of the retrieved studies.
Separate meta-analyses for case-control studies and cohort studies were conducted
using random-effects models, with results reported as adjusted odds ratios (ORs)
and relative risks (RRs), respectively. RESULTS: Thirteen studies--seven case
control studies and six population-based cohort studies--were included in this
meta-analysis. The pooled RR of the association between DM and POAG based on the
risk estimates of the six cohort studies was 1.40 (95% CI, 1.25-1.57). The pooled
OR of the association between DM and POAG based on the risk estimates of the
seven case-control studies was 1.49 (95% CI, 1.17-1.88). There was considerable
heterogeneity among the case-control studies that reported an association between
DM mellitus and POAG (P<0.001) and no significant heterogeneity among the cohort
studies (P = 0.377). After omitting the case-control study that contributed
significantly to the heterogeneity, the pooled OR for the association between DM
and POAG was 1.35 (95% CI, 1.06-1.74). CONCLUSIONS: Individuals with DM have an
increased risk of developing POAG.
PMID- 25137060
TI - Genomic inverse PCR for exploration of ligated breakpoints (GIPFEL), a new method
to detect translocations in leukemia.
AB - Here we present a novel method "Genomic inverse PCR for exploration of ligated
breakpoints" (GIPFEL) that allows the sensitive detection of recurrent
chromosomal translocations. This technique utilizes limited amounts of DNA as
starting material and relies on PCR based quantification of unique DNA sequences
that are created by circular ligation of restricted genomic DNA from
translocation bearing cells. Because the complete potential breakpoint region is
interrogated, a prior knowledge of the individual, specific interchromosomal
fusion site is not required. We validated GIPFEL for the five most common gene
fusions associated with childhood leukemia (MLL-AF4, MLL-AF9, MLL-ENL, ETV6
RUNX1, and TCF3-PBX1). A workflow of restriction digest, purification, ligation,
removal of linear fragments and precipitation enriching for circular DNA was
developed. GIPFEL allowed detection of translocation specific signature sequences
down to a 10-4 dilution which is close to the theoretical limit. In a blinded
proof-of-principle study utilizing DNA from cell lines and 144 children with B
precursor-ALL associated translocations this method was 100% specific with no
false positive results. Sensitivity was 83%, 65%, and 24% for t(4;11), t(9;11)
and t(11;19) respectively. Translocation t(12;21) was correctly detected in 64%
and t(1;19) in 39% of the cases. In contrast to other methods, the
characteristics of GIPFEL make it particularly attractive for prospective
studies.
PMID- 25137061
TI - A national survey of skin infections, care behaviors and MRSA knowledge in the
United States.
AB - A nationally representative sample of approximately 2000 individuals was surveyed
to assess SSTI infections over their lifetime and then prospectively over six
months. Knowledge of MRSA, future likelihood to self-treat a SSTI and self-care
behaviors was also queried. Chi square tests, linear and multinomial regression
were used for analysis. About 50% of those with a reported history of a SSTI
typical of MRSA had sought medical treatment. MRSA knowledge was low: 28% of
respondents could describe MRSA. Use of protective self-care behaviors that may
reduce transmission, such as covering a lesion, differed with knowledge of MRSA
and socio-demographics. Those reporting a history of a MRSA-like SSTI were more
likely to respond that they would self-treat than those without such a history
(OR 2.05 95% CI 1.40, 3.01; p<0.001). Since half of respondents reported not
seeking care for past lesions, incidence determined from clinical encounters
would greatly underestimate true incidence. MRSA knowledge was not associated
with seeking medical care, but was associated with self-care practices that may
decrease transmission.
PMID- 25137062
TI - The IkappaB kinase complex is required for plexin-B-mediated activation of RhoA.
AB - Plexins are widely expressed transmembrane proteins that mediate the cellular
effects of semaphorins. The molecular mechanisms of plexin-mediated signal
transduction are still poorly understood. Here we show that signalling via B
family plexins leading to the activation of the small GTPase RhoA requires
activation of the IkappaB kinase (IKK)-complex. In contrast, plexin-B-dependent
regulation of R-Ras activity is not affected by IKK activity. This regulation of
plexin signalling depends on the kinase activity of the IKK-complex, but is
independent of NF-kappaB activation. We confirm that the IKK-complex is active in
tumour cells and osteoblasts, and we demonstrate that plexin-B-dependent tumour
cell invasiveness and regulation of osteoblast differentiation require an active
IKK-complex. This study identifies a novel, NF-kappaB-independent function of the
IKK-complex and shows that IKK directs plexin-B signalling to the activation of
RhoA.
PMID- 25137064
TI - Conscious brain-to-brain communication in humans using non-invasive technologies.
AB - Human sensory and motor systems provide the natural means for the exchange of
information between individuals, and, hence, the basis for human civilization.
The recent development of brain-computer interfaces (BCI) has provided an
important element for the creation of brain-to-brain communication systems, and
precise brain stimulation techniques are now available for the realization of non
invasive computer-brain interfaces (CBI). These technologies, BCI and CBI, can be
combined to realize the vision of non-invasive, computer-mediated brain-to-brain
(B2B) communication between subjects (hyperinteraction). Here we demonstrate the
conscious transmission of information between human brains through the intact
scalp and without intervention of motor or peripheral sensory systems. Pseudo
random binary streams encoding words were transmitted between the minds of
emitter and receiver subjects separated by great distances, representing the
realization of the first human brain-to-brain interface. In a series of
experiments, we established internet-mediated B2B communication by combining a
BCI based on voluntary motor imagery-controlled electroencephalographic (EEG)
changes with a CBI inducing the conscious perception of phosphenes (light
flashes) through neuronavigated, robotized transcranial magnetic stimulation
(TMS), with special care taken to block sensory (tactile, visual or auditory)
cues. Our results provide a critical proof-of-principle demonstration for the
development of conscious B2B communication technologies. More fully developed,
related implementations will open new research venues in cognitive, social and
clinical neuroscience and the scientific study of consciousness. We envision that
hyperinteraction technologies will eventually have a profound impact on the
social structure of our civilization and raise important ethical issues.
PMID- 25137065
TI - Pyramidal cells make specific connections onto smooth (GABAergic) neurons in
mouse visual cortex.
AB - One of the hallmarks of neocortical circuits is the predominance of recurrent
excitation between pyramidal neurons, which is balanced by recurrent inhibition
from smooth GABAergic neurons. It has been previously described that in layer 2/3
of primary visual cortex (V1) of cat and monkey, pyramidal cells filled with
horseradish peroxidase connect approximately in proportion to the spiny
(excitatory, 95% and 81%, respectively) and smooth (GABAergic, 5% and 19%,
respectively) dendrites found in the neuropil. By contrast, a recent
ultrastructural study of V1 in a single mouse found that smooth neurons formed
51% of the targets of the superficial layer pyramidal cells. This suggests that
either the neuropil of this particular mouse V1 had a dramatically different
composition to that of V1 in cat and monkey, or that smooth neurons were
specifically targeted by the pyramidal cells in that mouse. We tested these
hypotheses by examining similar cells filled with biocytin in a sample of five
mice. We found that the average composition of the neuropil in V1 of these mice
was similar to that described for cat and monkey V1, but that the superficial
layer pyramidal cells do form proportionately more synapses with smooth dendrites
than the equivalent neurons in cat or monkey. These distributions may underlie
the distinct differences in functional architecture of V1 between rodent and
higher mammals.
PMID- 25137066
TI - Digital mapping of soil organic carbon contents and stocks in Denmark.
AB - Estimation of carbon contents and stocks are important for carbon sequestration,
greenhouse gas emissions and national carbon balance inventories. For Denmark, we
modeled the vertical distribution of soil organic carbon (SOC) and bulk density,
and mapped its spatial distribution at five standard soil depth intervals (0-5, 5
15, 15-30, 30-60 and 60-100 cm) using 18 environmental variables as predictors.
SOC distribution was influenced by precipitation, land use, soil type, wetland,
elevation, wetness index, and multi-resolution index of valley bottom flatness.
The highest average SOC content of 20 g kg(-1) was reported for 0-5 cm soil,
whereas there was on average 2.2 g SOC kg(-1) at 60-100 cm depth. For SOC and
bulk density prediction precision decreased with soil depth, and a standard error
of 2.8 g kg(-1) was found at 60-100 cm soil depth. Average SOC stock for 0-30 cm
was 72 t ha(-1) and in the top 1 m there was 120 t SOC ha(-1). In total, the
soils stored approximately 570 Tg C within the top 1 m. The soils under
agriculture had the highest amount of carbon (444 Tg) followed by forest and semi
natural vegetation that contributed 11% of the total SOC stock. More than 60% of
the total SOC stock was present in Podzols and Luvisols. Compared to previous
estimates, our approach is more reliable as we adopted a robust quantification
technique and mapped the spatial distribution of SOC stock and prediction
uncertainty. The estimation was validated using common statistical indices and
the data and high-resolution maps could be used for future soil carbon assessment
and inventories.
PMID- 25137068
TI - Nitrogen-enriched hierarchically porous carbons prepared from polybenzoxazine for
high-performance supercapacitors.
AB - Nitrogen-enriched hierarchically porous carbons (HPCs) were synthesized from a
novel nitrile-functionalized benzoxazine based on benzoxazine chemistry using a
soft-templating method and a potassium hydroxide (KOH) chemical activation method
and used as electrode materials for supercapacitors. The textural and chemical
properties could be easily tuned by adding a soft template and changing the
activation temperature. The introduction of the soft-templating agent (surfactant
F127) resulted in the formation of mesopores, which facilitated fast ionic
diffusion and reduced the internal resistance. The micropores of HPCs were
extensively developed by KOH activation to provide large electrochemical double
layer capacitance. As the activation temperature increased from 600 to 800
degrees C, the specific surface area of nitrogen-enriched carbons increased
dramatically, micropores were enlarged, and more meso/macropores were developed,
but the nitrogen and oxygen content decreased, which affected the electrochemical
performance. The sample HPC-800 activated at 800 degrees C possesses a high
specific surface area (1555.4 m(2) g(-1)), high oxygen (10.61 wt %) and nitrogen
(3.64 wt %) contents, a hierarchical pore structure, a high graphitization
degree, and good electrical conductivity. It shows great pseudocapacitance and
the largest specific capacitance of 641.6 F g(-1) at a current density of 1 A g(
1) in a 6 mol L(-1) KOH aqueous electrolyte when measured in a three-electrode
system. Furthermore, the HPC-800 electrode exhibits excellent rate capability
(443.0 F g(-1) remained at 40 A g(-1)) and good cycling stability (94.3%
capacitance retention over 5000 cycles).
PMID- 25137067
TI - Efficient in vivo deletion of a large imprinted lncRNA by CRISPR/Cas9.
AB - Recent genome-wide studies have revealed that the majority of the mouse genome is
transcribed as non-coding RNAs (ncRNAs) and growing evidence supports the
importance of ncRNAs in regulating gene expression and epigenetic processes.
However, the low efficiency of conventional gene targeting strategies has
hindered the functional study of ncRNAs in vivo, particularly in generating large
fragment deletions of long non-coding RNAs (lncRNAs) with multiple expression
variants. The bacterial clustered regularly interspaced short palindromic repeats
(CRISPR)/CRISPR-associated 9 (Cas9) system has recently been applied as an
efficient tool for engineering site-specific mutations of protein-coding genes in
the genome. In this study, we explored the potential of using the CRISPR/Cas9
system to generate large genomic deletions of lncRNAs in mice. We developed an
efficient one-step strategy to target the maternally expressed lncRNA, Rian, on
chromosome 12 in mice. We showed that paired sgRNAs can precisely generate large
deletions up to 23kb and the deletion efficiency can be further improved up to
33% by combining multiple sgRNAs. The deletion successfully abolished the
expression of Rian from the maternally inherited allele, validating the
biological relevance of the mutations in studying an imprinted locus. Mutation of
Rian has differential effects on expression of nearby genes in different somatic
tissues. Taken together, we have established a robust one-step method to engineer
large deletions to knockout lncRNA genes with the CRISPR/Cas9 system. Our work
will facilitate future functional studies of other lncRNAs in vivo.
PMID- 25137063
TI - Toxicological profile of ultrapure 2,2',3,4,4',5,5'-heptachlorbiphenyl (PCB 180)
in adult rats.
AB - PCB 180 is a persistent non-dioxin-like polychlorinated biphenyl (NDL-PCB)
abundantly present in food and the environment. Risk characterization of NDL-PCBs
is confounded by the presence of highly potent dioxin-like impurities. We used
ultrapure PCB 180 to characterize its toxicity profile in a 28-day repeat dose
toxicity study in young adult rats extended to cover endocrine and behavioral
effects. Using a loading dose/maintenance dose regimen, groups of 5 males and 5
females were given total doses of 0, 3, 10, 30, 100, 300, 1000 or 1700 mg PCB
180/kg body weight by gavage. Dose-responses were analyzed using benchmark dose
modeling based on dose and adipose tissue PCB concentrations. Body weight gain
was retarded at 1700 mg/kg during loading dosing, but recovered thereafter. The
most sensitive endpoint of toxicity that was used for risk characterization was
altered open field behavior in females; i.e. increased activity and distance
moved in the inner zone of an open field suggesting altered emotional responses
to unfamiliar environment and impaired behavioral inhibition. Other dose
dependent changes included decreased serum thyroid hormones with associated
histopathological changes, altered tissue retinoid levels, decreased hematocrit
and hemoglobin, decreased follicle stimulating hormone and luteinizing hormone
levels in males and increased expression of DNA damage markers in liver of
females. Dose-dependent hypertrophy of zona fasciculata cells was observed in
adrenals suggesting activation of cortex. There were gender differences in
sensitivity and toxicity profiles were partly different in males and females. PCB
180 adipose tissue concentrations were clearly above the general human population
levels, but close to the levels in highly exposed populations. The results
demonstrate a distinct toxicological profile of PCB 180 with lack of dioxin-like
properties required for assignment of WHO toxic equivalency factor. However, PCB
180 shares several toxicological targets with dioxin-like compounds emphasizing
the potential for interactions.
PMID- 25137069
TI - Hope for the best or prepare for the worst? Towards a spatial cognitive bias test
for mice.
AB - Cognitive bias, the altered information processing resulting from the background
emotional state of an individual, has been suggested as a promising new indicator
of animal emotion. Comparable to anxious or depressed humans, animals in a
putatively negative emotional state are more likely to judge an ambiguous
stimulus as if it predicts a negative event, than those in positive states. The
present study aimed to establish a cognitive bias test for mice based on a
spatial judgment task and to apply it in a pilot study to serotonin transporter
(5-HTT) knockout mice, a well-established mouse model for the study of anxiety-
and depression-related behavior. In a first step, we validated that our setup can
assess different expectations about the outcome of an ambiguous stimulus: mice
having learned to expect something positive within a maze differed significantly
in their behavior towards an unfamiliar location than animals having learned to
expect something negative. In a second step, the use of spatial location as a
discriminatory stimulus was confirmed by showing that mice interpret an ambiguous
stimulus depending on its spatial location, with a position exactly midway
between a positive and a negative reference point provoking the highest level of
ambiguity. Finally, the anxiety- and depression-like phenotype of the 5-HTT
knockout mouse model manifested--comparable to human conditions--in a trend for a
negatively distorted interpretation of ambiguous information, albeit this effect
was not statistically significant. The results suggest that the present cognitive
bias test provides a useful basis to study the emotional state in mice, which may
not only increase the translational value of animal models in the study of human
affective disorders, but which is also a central objective of animal welfare
research.
PMID- 25137070
TI - Catalytic profile of Arabidopsis peroxidases, AtPrx-2, 25 and 71, contributing to
stem lignification.
AB - Lignins are aromatic heteropolymers that arise from oxidative coupling of lignin
precursors, including lignin monomers (p-coumaryl, coniferyl, and sinapyl
alcohols), oligomers, and polymers. Whereas plant peroxidases have been shown to
catalyze oxidative coupling of monolignols, the oxidation activity of well
studied plant peroxidases, such as horseradish peroxidase C (HRP-C) and AtPrx53,
are quite low for sinapyl alcohol. This characteristic difference has led to
controversy regarding the oxidation mechanism of sinapyl alcohol and lignin
oligomers and polymers by plant peroxidases. The present study explored the
oxidation activities of three plant peroxidases, AtPrx2, AtPrx25, and AtPrx71,
which have been already shown to be involved in lignification in the Arabidopsis
stem. Recombinant proteins of these peroxidases (rAtPrxs) were produced in
Escherichia coli as inclusion bodies and successfully refolded to yield their
active forms. rAtPrx2, rAtPrx25, and rAtPrx71 were found to oxidize two syringyl
compounds (2,6-dimethoxyphenol and syringaldazine), which were employed here as
model monolignol compounds, with higher specific activities than HRP-C and
rAtPrx53. Interestingly, rAtPrx2 and rAtPrx71 oxidized syringyl compounds more
efficiently than guaiacol. Moreover, assays with ferrocytochrome c as a substrate
showed that AtPrx2, AtPrx25, and AtPrx71 possessed the ability to oxidize large
molecules. This characteristic may originate in a protein radical. These results
suggest that the plant peroxidases responsible for lignin polymerization are able
to directly oxidize all lignin precursors.
PMID- 25137071
TI - Circulating miR-19a and miR-205 in serum may predict the sensitivity of luminal A
subtype of breast cancer patients to neoadjuvant chemotherapy with epirubicin
plus paclitaxel.
AB - BACKGROUND: The luminal A subtype of breast cancer has a good prognosis and is
sensitive to endocrine therapy but is less sensitive to chemotherapy. It is
necessary to identify biomarkers to predict chemosensitivity and avoid over
treatment. We hypothesized that miRNAs in the serum might be associated with
chemosensitivity. METHODS: Sixty-eight breast cancer patients received
neoadjuvant chemotherapy with epirubicin plus paclitaxel. The serum of the
patients was collected before chemotherapy and stored at -80 degrees C. The
samples were classified into two groups in term of the chemosensitivity. We
identified the differential expression patterns of miRNAs between the
chemotherapy sensitive and resistant groups using microRNA profiling. Four miRNAs
that were differentially expressed between the two groups were further validated
in another 56 samples. We created a model fitting formula and a receiver
operating characteristics (ROC) curve using logistic regression analysis to
evaluate the prediction potency. RESULTS: We identified 8 miRNAs differentially
expressed between the two groups: 6 miRNAs were up-regulated, and 2 miRNAs were
down-regulated in the resistant group compared with the sensitive group. The
expression of miR-19a and miR-205 were determined to have significant differences
between the two groups (P<0.05). A predictive model of these two miRNAs was
created by the logistic regression analysis. The probability of this model was
89.71%. Based on the ROC curve, the specificity was 75.00%, and the sensitivity
was 81.25%. CONCLUSIONS: The combination of miR-19a and miR-205 in the serum may
predict the chemosensitivity of luminal A subtype of breast cancer to epirubicin
plus paclitaxel neoadjuvant chemotherapy.
PMID- 25137072
TI - The free caesareans policy in low-income settings: an interrupted time series
analysis in Mali (2003-2012).
AB - INTRODUCTION: Several countries have instituted fee exemptions for caesareans to
reduce maternal and newborn mortality. OBJECTIVES: To evaluate the effect of fee
exemptions for caesareans on population caesarean rates taking into account
different levels of accessibility. METHODS: The observation period was from
January 2003 to May 2012 in one Region and covered 11.7 million person-years.
Exemption fees for caesareans were adopted on June 26, 2005. Data were obtained
from a registration system implemented in 2003 that tracks all obstetrical
emergencies and interventions including caesareans. The pre-intervention period
was 30 months and the post-intervention period was 83 months. We used an
interrupted time series to evaluate the trend before and after the policy
adoption and the overall tendency. FINDINGS: During the study period, the
caesarean rate increased from 0.25 to 1.5% for the entire population. For women
living in cities with district hospitals that provided caesareans, the rate
increased from 1.7% before the policy was enforced to 5.7% 83 months later. No
significant change in trends was observed among women living in villages with a
healthcare centre or those in villages with no healthcare facility. For the
latter, the caesarean rate increased from 0.4 to 1%. CONCLUSIONS: After nine
years of implementation policy in Mali, the caesarean rate achieved in cities
with a district hospital reached the full beneficial effect of this measure,
whereas for women living elsewhere this policy did not increase the caesarean
rate to a level that could contribute effectively to reduce their risk of
maternal death. Only universal access to this essential intervention could reduce
the inequities and increase the effectiveness of this policy.
PMID- 25137073
TI - pH dependence of conformational fluctuations of the protein backbone.
AB - Proton binding equilibria (pK(a) values) of ionizable groups in proteins are
exquisitely sensitive to their microenvironments. Apparent pK(a) values measured
for individual ionizable residues with NMR spectroscopy are actually population
weighted averages of the pK(a) in different conformational microstates. NMR
spectroscopy experiments with staphylococcal nuclease were used to test the
hypothesis that pK(a) values of surface Glu and Asp residues are affected by pH
sensitive fluctuations of the backbone between folded and locally unfolded
conformations. (15)N spin relaxation studies showed that as the pH decreases from
the neutral into the acidic range the amplitudes of backbone fluctuations in the
ps-ns timescale increase near carboxylic residues. Hydrogen exchange experiments
suggested that backbone conformational fluctuations promoted by decreasing pH
also reflect slower local or sub-global unfolding near carboxylic groups. This
study has implications for structure-based pKa calculations: (1) The timescale of
the backbone's response to ionization events in proteins can range from ps to ms,
and even longer; (2) pH-sensitive fluctuations of the backbone can be localized
to both the segment the ionizable residue is attached to or the one that occludes
the ionizable group; (3) Structural perturbations are not necessarily propagated
through Coulomb interactions; instead, local fluctuations appear to be coupled
through the co-operativity inherent to elements of secondary structure and to
networks of hydrogen bonds. These results are consistent with the idea that local
conformational fluctuations and stabilities are important determinants of
apparent pK(a) values of ionizable residues in proteins.
PMID- 25137075
TI - Obstetric triage.
PMID- 25137074
TI - Orthology detection combining clustering and synteny for very large datasets.
AB - The elucidation of orthology relationships is an important step both in gene
function prediction as well as towards understanding patterns of sequence
evolution. Orthology assignments are usually derived directly from sequence
similarities for large data because more exact approaches exhibit too high
computational costs. Here we present PoFF, an extension for the standalone tool
Proteinortho, which enhances orthology detection by combining clustering,
sequence similarity, and synteny. In the course of this work, FFAdj-MCS, a
heuristic that assesses pairwise gene order using adjacencies (a similarity
measure related to the breakpoint distance) was adapted to support multiple
linear chromosomes and extended to detect duplicated regions. PoFF largely
reduces the number of false positives and enables more fine-grained predictions
than purely similarity-based approaches. The extension maintains the low memory
requirements and the efficient concurrency options of its basis Proteinortho,
making the software applicable to very large datasets.
PMID- 25137076
TI - Should informed consent be required for routine newborn screening and for the
storage of blood samples?
PMID- 25137079
TI - Subsequent pregnancy after having a baby who was hospitalized in the NICU.
AB - PURPOSE: To understand experiences of mothers who had a baby hospitalized in the
NICU and then decided to have another pregnancy. STUDY DESIGN AND METHODS: We
used a descriptive phenomenological approach to study 12 mothers in Japan who had
a child hospitalized in the NICU and had a subsequent child. Data were collected
by semistructured interviews that occurred two to four times per participant.
Data were analyzed using Colaizzi's method. RESULTS: Although all of the mothers
had a child who was making steady progress, they experienced difficulty when
deciding on having another pregnancy. Our analysis identified five theme
clusters: delaying pregnancy; unwavering view about having subsequent children;
changing values regarding pregnancy and childbirth; relief of anxiety and fear
about repeated hospitalization in the NICU; and preparedness to accept the
outcome of pregnancy. CLINICAL IMPLICATIONS: Our study suggests that mothers
require support during babies' hospitalization in the NICU and for the process of
decision-making about a subsequent pregnancy. Family-centered care as the basis
for nursing practice in the NICU is ideal to provide this type of support.
PMID- 25137078
TI - Women's perspectives on falls and fall prevention during pregnancy.
AB - BACKGROUND: Falls are the leading cause of unintentional injury in women. During
pregnancy, even a minor fall can result in adverse consequences. Evidence to
inform effective and developmentally appropriate pregnancy fall prevention
programs is lacking. Early research on pregnancy fall prevention suggests that
exercise may reduce falls. However, acceptability and effectiveness of pregnancy
fall prevention programs are untested. PURPOSE: To better understand postpartum
women's perspective and preferences on fall prevention strategies during
pregnancy to formulate an intervention. METHODS: Focus groups and individual
interviews were conducted with 31 postpartum women using descriptive qualitative
methodology. Discussion of falls during pregnancy and fall prevention strategies
was guided by a focus group protocol and enhanced by 1- to 3-minute videos on
proposed interventions. Focus groups were audio recorded, transcribed, and
analyzed using NVivo 10 software. RESULTS: Emerging themes were environmental
circumstances and physical changes of pregnancy leading to a fall, prevention
strategies, barriers, safety concerns, and marketing a fall prevention program.
Wet surfaces and inappropriate footwear commonly contributed to falls. Women
preferred direct provider counseling and programs including yoga and Pilates.
IMPLICATIONS: Fall prevention strategies tailored to pregnant women are needed.
Perspectives of postpartum women support fall prevention through provider
counseling and individual or supervised exercise programs.
PMID- 25137080
TI - Breast cancer risk assessment in primary care.
AB - Breast cancer is the most common cancer (when excluding skin cancers) in women
and the second most common cause of cancer death in women, with a lifetime
prevalence of 12.5% (, ; ). Breast cancer screening reduces risk of cancer death,
thereby increasing rate of survival to up to 89% for women with stage 1 and 2
breast cancer (; ). Despite these data, undue harm may occur with unnecessary
screening because overidentification of risk, and excessive, costly biopsies may
result. Costs and benefits of screening must be weighed. Nurses at all levels can
play a pivotal role in promotion of appropriate breast cancer screening and
subsequently breast cancer prevention by using accurate screening tools, such as
the Tyrer-Cuzick model. Although there are some limitations with this tool,
screening at the primary care level has demonstrated improved clinical outcomes
(). Its use can help nurses accurately assess a woman's breast cancer risk, by
promoting appropriate screening at the primary care level ().
PMID- 25137081
TI - Parenting and concerns of pregnant women in buprenorphine treatment.
AB - PURPOSE: Opioid-dependent pregnant women are characterized by drug use during
pregnancy and deficits in knowledge of newborn care and feeding, and of child
development. We assessed parenting skills and concerns among pregnant women in
buprenorphine treatment for prescription opioid dependence. STUDY DESIGN AND
METHODS: We interviewed 32 pregnant women who received buprenorphine treatment
for prescription opioid dependence in a primary care setting and administered
questionnaires, including the Adult-Adolescent Parenting Inventory version 2
(AAPI-2) and Childhood Experience of Care and Abuse Questionnaire. RESULTS: AAPI
2 scores revealed medium risk of abuse for all five scales: inappropriate
expectations of the child, low level of empathy, strong belief in corporal
punishment, reversal of parent-child roles, and oppression of children's power
and independence. Primary concerns of participants were neonatal abstinence
syndrome (NAS) and their child's health. Pregnant women who received
buprenorphine for treatment of prescription opioid dependence showed a lack of
appropriate parenting skills, but did not express concern about their ability to
parent. CLINICAL IMPLICATIONS: Our findings suggest a need for nurses to assist
prescription opioid-dependent pregnant women in acquiring additional parenting
skills, to refer for educational parenting intervention, and to educate patients
about NAS.
PMID- 25137083
TI - Potential tools to assess diet quality.
PMID- 25137082
TI - Women's experience of decision-making with medication abortion.
AB - BACKGROUND: Medication abortion received regulatory approval in 2001 in the
United States with healthcare providers increasingly offering this method.
However, most studies in the United States have only explored acceptability and
decision-making with women who participated in clinical trials. Overall, the
literature on women's experience with a method that it is now widely available is
under research in the United States. OBJECTIVE: To describe and analyze the
women's experience as they choose the option of and experienced the process of
medication abortion. DESIGN: A constructivist grounded theory study. SETTING:
Outpatient clinical offices in a three-state area in the northeast region of the
United States. PARTICIPANTS: A purposive sample of 22 women aged 16 to 45 who
experienced a medication abortion. METHODS: Data were collected by in-depth, open
ended, face-to-face interviews. The constant comparative method was used for
analysis. RESULTS: Five interwoven categories emerged regarding women's initial
decision to have a medication abortion: choosing a natural process, avoiding
"surgery," respecting the "baby," scheduling to meet needs, and appreciating the
home setting. The enhanced sense of personal control associated with the
medication abortion option was the overriding reason given for choosing this
method. CONCLUSION: This study contributes to the paucity of literature on the
reasons why women choose medication abortion. It is important for nurses to
understand the complexity of medication abortion decision-making so that they can
effectively support women through this process.
PMID- 25137084
TI - Human factors, usability, and the electronic health record.
PMID- 25137085
TI - Fostering hope: documenting interventions targeting Ethiopian child brides.
PMID- 25137087
TI - Underwater birth: an elective intervention with safety concerns.
PMID- 25137088
TI - Synthesis of sulfur-bridged polycycles via Pd-catalyzed dehydrogenative
cyclization.
AB - A general approach to sulfur-bridged polycycles by palladium-catalyzed double
C(sp(2))-H bond oxidative cyclization is presented. This protocol afforded
diverse sulfur-bridged five-, six-, and seven-membered polycycles in moderate to
good yields with a tolerance for a wide variety of functional groups. A sulfide
bridged six-membered pyrene-thienoacene compound was synthesized readily using
this method, and excellent performance for photoluminescence quantum yield was
observed.
PMID- 25137089
TI - Quantitative measurement of ligand exchange on iron oxides via radiolabeled oleic
acid.
AB - Ligand exchange of hydrophilic molecules on the surface of hydrophobic iron oxide
nanoparticles produced via thermal decomposition of chelated iron precursors is a
common method for producing aqueous suspensions of particles for biomedical
applications. Despite the wide use, relatively little is understood about the
efficiency of ligand exchange on the surface of iron oxide nanoparticles and how
much of the hydrophobic ligand is removed. To address this issue, we utilized a
radiotracer technique to track the exchange of a radiolabeled (14)C-oleic acid
ligand with hydrophilic ligands on the surface of magnetite nanoparticles. Iron
oxide nanoparticles functionalized with (14)C-oleic acid were modified with
poly(ethylene glycol) with terminal functional groups including, L-3,4
dihydroxyphenylalanine, a nitrated L-3,4-dihydroxyphenylalanine, carboxylic acid,
a phosphonate, and an amine. Following ligand exchange, the nanoparticles and
byproducts were analyzed using liquid scintillation counting and inductively
coupled plasma mass spectroscopy. The labeled and unlabeled particles were
further characterized by transmission electron microscopy and dynamic light
scattering to determine particle size, hydrodynamic diameter, and zeta potential.
The unlabeled particles were characterized via thermogravimetric analysis and
vibrating sample magnetometry. Radioanalytical determination of the (14)C from
(14)C-oleic acid was used to calculate the amount of oleic acid remaining on the
surface of the particles after purification and ligand exchange. There was a
significant loss of oleic acid on the surface of the particles after ligand
exchange with amounts varying for the different functional binding groups on the
poly(ethylene glycol). Nonetheless, all samples demonstrated some residual oleic
acid associated with the particles. Quantification of the oleic acid remaining
after ligand exchange reveals a binding hierarchy in which catechol derived
anchor groups displace oleic acid on the surface of the nanoparticles better than
the phosphonate, followed by the amine and carboxylic acid groups. Furthermore,
the results show that these ligand exchange reactions do not necessarily occur to
completion as is often assumed, thus leaving a residual amount of oleic acid on
the surface of the particles. A thorough analysis of ligand exchange is required
to develop nanoparticles that are suitable for their desired application.
PMID- 25137091
TI - International nursing partnerships for global cancer control.
PMID- 25137090
TI - The effect of temperature on the catalytic conversion of Kraft lignin using near
critical water.
AB - The catalytic conversion of suspended LignoBoost Kraft lignin was performed in
near-critical water using ZrO2/K2CO3 as the catalytic system and phenol as the co
solvent and char suppressing agent. The reaction temperature was varied from 290
to 370 degrees C and its effect on the process was investigated in a continuous
flow (1kg/h). The yields of water-soluble organics (WSO), bio-oil and char (dry
lignin basis) were in the ranges of 5-11%, 69-87% and 16-22%, respectively. The
bio-oil, being partially deoxygenated, exhibited higher carbon content and heat
value, but lower sulphur content than lignin. The main 1-ring aromatics (in WSO
and diethylether-soluble bio-oil) were anisoles, alkylphenols, catechols and
guaiacols. The results show that increasing temperature increases the yield of 1
ring aromatics remarkably, while it increases the formation of char moderately.
An increase in the yields of anisoles, alkylphenols and catechols, together with
a decrease in the yield of guaiacols, was also observed.
PMID- 25137093
TI - Cancer in the aging: what are we doing to family caregivers?
PMID- 25137092
TI - End-of-life care pathways for improving outcomes in caring for the dying.
PMID- 25137094
TI - Panning for the gold in health research: incorporating studies' methodological
quality in meta-analysis.
AB - BACKGROUND: Systematic reviews now routinely assess methodological quality to
gauge the validity of the included studies and of the synthesis as a whole.
Although trends from higher quality studies should be clearer, it is uncertain
how often meta-analyses incorporate methodological quality in models of study
results either as predictors, or, more interestingly, in interactions with
theoretical moderators. OBJECTIVE AND METHODS: We survey 200 meta-analyses in
three health promotion domains to examine when and how meta-analyses incorporate
methodological quality. RESULTS: Although methodological quality assessments
commonly appear in contemporary meta-analyses (usually as scales), they are
rarely incorporated in analyses, and still more rarely analysed in interaction
with theoretical determinants of the success of health promotions. The few meta
analyses (2.5%) that did include such an interaction analysis showed that
moderator results remained significant in higher quality studies or were present
only among higher quality studies. We describe how to model quality interactively
with theoretically derived moderators and discuss strengths and weaknesses of
this approach and in relation to current meta-analytic practice. CONCLUSIONS: In
large literatures exhibiting heterogeneous effects, meta-analyses can incorporate
methodological quality and generate conclusions that enable greater confidence
not only about the substantive phenomenon but also about the role that
methodological quality itself plays.
PMID- 25137095
TI - High proton conduction at above 100 degrees C mediated by hydrogen bonding in a
lanthanide metal-organic framework.
AB - A lanthanide metal-organic framework (MOF) compound of the formulation
[Eu2(CO3)(ox)2(H2O)2].4H2O (1, ox = oxalate) was prepared by hydrothermal
synthesis with its structure determined crystallographically. Temperature
dependent but humidity-independent high proton conduction was observed with a
maximum of 2.08 * 10(-3) S cm(-1) achieved at 150 degrees C, well above the
normal boiling point of water. Results from detailed structural analyses,
comparative measurements of conductivities using regular and deuterated samples,
anisotropic conductivity measurements using a single-crystal sample, and variable
temperature photoluminescence studies collectively establish that the protons
furnished by the Eu(III)-bound and activated aqua ligands are the charge carriers
and that the transport of proton is mediated along the crystallographic a-axis by
ordered hydrogen-bonded arrays involving both aqua ligands and adjacent oxalate
groups in the channels of the open framework. Proton conduction was enhanced with
the increase of temperature from room temperature to about 150 degrees C, which
can be rationalized in terms of thermal activation of the aqua ligands and the
facilitated transport between aqua and adjacent oxalate ligands. A complete
thermal loss of the aqua ligands occurred at about 160 degrees C, resulting in
the disintegration of the hydrogen-bonded pathway for proton transport and a
precipitous drop in conductivity. However, the structural integrity of the MOF
was maintained up to 350 degrees C, and upon rehydration, the original structure
with the hydrogen-bonded arrays was restored, and so was its high proton
conduction ability.
PMID- 25137097
TI - The geographic origin of Helicobacter pylori isolated from Costa Rican patients.
AB - Helicobacter pylori infects a significant proportion of the world population and
it is associated with pathologies which include chronic atrophic gastritis,
peptic ulcer, and gastric neoplasias such as gastric adenocarcinoma and MALT
lymphoma. Costa Rica has a high prevalence of the infection and an elevated
incidence of gastric cancer and its associated mortality. The global population
structure for H. pylori has been established using a MLST scheme. The population
structure of the strains of H. pylori circulating in Costa Rica is currently
unknown. We characterized the geographical origin of 24 H. pylori isolates from
Costa Rican patients. We identified 142 new alleles for the genes included in the
scheme and in eight of the 24 isolates from Costa Rican patients, all seven
alleles sequenced were described for the first time. Twenty-one isolates from
Costa Rican patients group with hpEurope strains and the remaining three isolates
grouped with hspWAfrica isolates (Bayesian posterior probability values above
0.70, P = 0.05, after 2 000 000 generations). The obtained result in the MLST
analysis was not unexpected and reflects the genetic composition of the Costa
Rican population.
PMID- 25137098
TI - Tax fraud.
PMID- 25137099
TI - Hiring scribes.
PMID- 25137096
TI - Virulence and draft genome sequence overview of multiple strains of the swine
pathogen Haemophilus parasuis.
AB - Haemophilus parasuis is the cause of Glasser's disease in swine, which is
characterized by systemic infection resulting in polyserositis, meningitis, and
arthritis. Investigation of this animal disease is complicated by the enormous
differences in the severity of disease caused by H. parasuis strains, ranging
from lethal systemic disease to subclinical carriage. To identify differences in
genotype that could account for virulence phenotypes, we established the
virulence of, and performed whole genome sequence analysis on, 11 H. parasuis
strains. Virulence was assessed by evaluating morbidity and mortality following
intranasal challenge of Caesarean-derived, colostrum-deprived (CDCD) pigs.
Genomic DNA from strains Nagasaki (serotype 5), 12939 (serotype 1), SW140
(serotype 2), 29755 (serotype 5), MN-H (serotype 13), 84-15995 (serotype 15),
SW114 (serotype 3), H465 (serotype 11), D74 (serotype 9), and 174 (serotype 7)
was used to generate Illumina paired-end libraries for genomic sequencing and de
novo assembly. H. parasuis strains Nagasaki, 12939, SH0165 (serotype 5), SW140,
29755, and MN-H exhibited a high level of virulence. Despite minor differences in
expression of disease among these groups, all pigs challenged with these strains
developed clinical signs consistent with Glasser's disease between 1-7 days post
challenge. H. parasuis strains 84-15995 and SW114 were moderately virulent, in
that approximately half of the pigs infected with each developed Glasser's
disease. H. parasuis strains H465, D74, and 174 were minimally virulent or
avirulent in the CDCD pig model. Comparative genomic analysis among strains
identified several noteworthy differences in coding regions. These coding regions
include predicted outer membrane, metabolism, and pilin or adhesin related genes,
some of which likely contributed to the differences in virulence and systemic
disease observed following challenge. These data will be useful for identifying
H. parasuis virulence factors and vaccine targets.
PMID- 25137100
TI - Seeking simplicity.
PMID- 25137101
TI - Protecting the family.
PMID- 25137102
TI - Leading the charge.
PMID- 25137103
TI - Casting a vision.
PMID- 25137104
TI - Public mental health.
PMID- 25137105
TI - Social determinants of mental health.
AB - A person's mental health and many common mental disorders are shaped by various
social, economic, and physical environments operating at different stages of
life. Risk factors for many common mental disorders are heavily associated with
social inequalities, whereby the greater the inequality the higher the inequality
in risk. The poor and disadvantaged suffer disproportionately, but those in the
middle of the social gradient are also affected. It is of major importance that
action is taken to improve the conditions of everyday life, beginning before
birth and progressing into early childhood, older childhood and adolescence,
during family building and working ages, and through to older age. Action
throughout these life stages would provide opportunities for both improving
population mental health, and for reducing risk of those mental disorders that
are associated with social inequalities. As mental disorders are fundamentally
linked to a number of other physical health conditions, these actions would also
reduce inequalities in physical health and improve health overall. Action needs
to be universal: across the whole of society and proportionate to need. Policy
making at all levels of governance and across sectors can make a positive
difference.
PMID- 25137106
TI - Mental disability, human rights and the capabilities approach: searching for the
foundations.
AB - Those seeking to improve the well-being of individuals with disabilities
worldwide often draw on the idea of human rights. More recently, a variety of
international human rights legislation such as the Convention on the Rights of
Persons with Disabilities (CRPD) has come into force worldwide. The present
article aims to ground human rights of people with disabilities such as those in
the CRPD in a theory of social justice called the capabilities approach (CA).
This article discusses the reasons for grounding rights in a theory of justice,
the links between the CA and human rights, the central concern for disability and
individuals with disabilities in the CA, and seven central components of the CA.
PMID- 25137107
TI - Climate change: the next challenge for public mental health?
AB - Climate change is increasingly recognized as one of the greatest threats to human
health of the 21st century, with consequences that mental health professionals
are also likely to face. While physical health impacts have been increasingly
emphasized in literature and practice, recent scholarly literature indicates that
climate change and related weather events and environmental changes can
profoundly impact psychological well-being and mental health through both direct
and indirect pathways, particularly among those with pre-existing vulnerabilities
or those living in ecologically sensitive areas. Although knowledge is still
limited about the connections between climate change and mental health, evidence
is indicating that impacts may be felt at both the individual and community
levels, with mental health outcomes ranging from psychological distress,
depression and anxiety, to increased addictions and suicide rates. Drawing on
examples from diverse geographical areas, this article highlights some climate
sensitive impacts that may be encountered by mental health professionals. We then
suggest potential avenues for public mental health in light of current and
projected changes, in order to stimulate thought, debate, and action.
PMID- 25137108
TI - Evaluation of a comedy intervention to improve coping and help-seeking for mental
health problems in a women's prison.
AB - Rates of mental illness and self-harm are very high among women prisoners.
Questionnaires assessed prisoners' knowledge of and attitudes towards mental
health problems, and relevant behavioural intentions before and after the
intervention, to evaluate the effectiveness of a comedy show in a women's prison
to reduce mental health stigma and improve coping and help-seeking for mental
health problems. The intervention appeared to have been successful in improving
some aspects of prisoners' knowledge about the effectiveness of psychotherapy (Z
= - 2.304, p = 0.021) and likelihood of recovery from mental health problems (Z =
- 2.699, p = 0.007). There were significant post-intervention increases in the
proportion who stated they would discuss or disclose mental health problems with
all but one of the sources of help in the questionnaire, which was consistent
with the increases in the number of prisoners who rated themselves as likely to
start using different sources of help or prison activities. There was no
improvement in intentions to associate with people with a mental health problem.
The intervention appeared effective in improving factors that might increase help
seeking and improve coping, but not those that would change behaviour towards
others with a mental health problem.
PMID- 25137109
TI - Disclosure of domestic violence in mental health settings: a qualitative meta
synthesis.
AB - Little is known about how psychiatric services respond to service users'
experiences of domestic violence. This qualitative meta-synthesis examined the
healthcare experiences and expectations of mental health service users
experiencing domestic violence. Twenty-two biomedical, social science, grey
literature databases and websites were searched, supplemented by citation
tracking and expert recommendations. Qualitative studies which included mental
health service users (aged >= 16 years) with experiences of domestic violence
were eligible for inclusion. Two reviewers independently extracted data from
included papers and assessed quality. Findings from primary studies were combined
using meta-synthesis techniques. Twelve studies provided data on 140 female and
four male mental health service users. Themes were generally consistent across
studies. Overarching theoretical constructs included the role of professionals in
identifying domestic violence and facilitating disclosures, implementing
personalized care and referring appropriately. Mental health services often
failed to identify and facilitate disclosures of domestic violence, and to
develop responses that prioritized service users' safety. Mental health services
were reported to give little consideration to the role of domestic violence in
precipitating or exacerbating mental illness and the dominance of the biomedical
model and stigma of mental illness were found to inhibit effective responses.
Mental health services often fail to adequately address the violence experienced
by mental health service users. This meta-synthesis highlights the need for
mental health services to establish appropriate strategies and responses to
domestic violence to ensure optimal care of this vulnerable population.
PMID- 25137110
TI - A public health initiative for reducing access to pesticides as a means to
committing suicide: findings from a qualitative study.
AB - Widespread use of pesticides among farmers in rural India, provides an easy means
for suicide. A public health initiative involving storage of pesticides in a
central storage facility could be a possible strategy for reducing mortality and
morbidity related to pesticide poisoning. This qualitative study explored
community perceptions towards a central pesticide storage facility in villages in
rural South India. Sixteen focus group discussions held with consenting adults
from intervention and control villages were followed by eight more a year after
initiation of the storage facility. Analysis revealed four themes, namely,
reasons for committing suicide and methods used, exposure to pesticides and first
aid practices, storage and disposal of pesticides, and perceptions towards the
storage facility. The facility was appreciated as a means of preventing suicides
and for providing a safe haven for pesticide storage. The participatory process
that guided its design, construction and location ensured its acceptability. Use
of qualitative methods helped provide deep insights into the phenomenon of
pesticide suicide and aided the understanding of community perceptions towards
the storage facility. The study suggests that communal storage of pesticides
could be an important step towards reducing pesticide suicides in rural areas.
PMID- 25137111
TI - Building mental health workforce capacity through training and retention of
psychiatrists in Zimbabwe.
AB - Despite the need to improve the quantity and quality of psychiatry training in
sub-Saharan Africa (SSA), very little is known about the experiences of
psychiatric trainees in the region. This is the first study examining psychiatric
trainees in a low-income country in SSA. It was carried out as part of the needs
assessment for a unique Medical Education Partnership Initiative (MEPI) programme
to find African solutions for medical shortages in Africa. We approached all
doctors who had trained in post-graduate psychiatry in Zimbabwe in 2010 and
conducted in-depth qualitative interviews with all except one (n = 6). We
analysed the data using constant comparison and thematic analysis. Trainees
described the apprenticeship model as the programme's primary strength, through
providing clinical exposure and role models. Programme weaknesses included
shortages in information sources, trainee salaries, trainers, public health
education, and in the mental health service. Most respondents were, however,
eager to continue practising psychiatry in Zimbabwe, motivated by family ties,
national commitment and helping vulnerable, stigmatized individuals. Respondents
called for sub-speciality training and for infrastructure and training to do
research. Resources need to be made available for psychiatric trainees in more
SSA settings to develop public health competencies. However, investment in
psychiatry training programmes must balance service provision with trainees'
educational needs. Directing investment towards needs identified by trainees may
be a cost-effective, context-sensitive way to increase retention and learning
outcomes.
PMID- 25137112
TI - Corporate social responsibility and mental health: the Premier League football
Imagine Your Goals programme.
AB - Football is increasingly used to facilitate recovery in mental health services,
often in partnership with football clubs. However, few clubs have made mental
health part of their corporate social responsibility programmes until recently.
We report the impact on participants of the 'Imagine Your Goals' programme, run
by 16 Premier League football clubs in conjunction with England's Time to Change
programme to reduce mental health-related stigma and discrimination. Mixed
methods evaluation used pre/post measures of well-being, access to social
capital, focus groups held early on and towards the end of the two-year
programmes, and questionnaires for coaching staff. There were no significant
changes to participants' mental well-being scores between baseline and follow-up,
nor to the total number of social resources accessible through their networks.
However, there was a statistically significant increase at follow-up in the mean
score of the personal skills subscale of the Resource Generator-UK. Participants'
individual skills were also higher at follow-up. Qualitative data showed
programmes had largely met participants' expectations in terms of socializing,
providing structure and improving fitness levels, exceeded expectations in
relationships with coaching staff and additional activities, but did not always
meet them in improving football skills. Participants varied in their knowledge of
exit opportunities, depending on which club's programme they attended. A minority
of clubs reported difficulties in recruitment and concerns about planning for the
future of the projects. Football clubs and the charitable foundations they set up
can successfully deliver programmes to people with mental health problems which
improve access to personal skills social capital and have other potential
benefits.
PMID- 25137113
TI - Mental Health First Aid is an effective public health intervention for improving
knowledge, attitudes, and behaviour: a meta-analysis.
AB - Mental Health First Aid (MHFA) is a standardized, psychoeducational programme
developed to empower the public to approach, support and refer individuals in
distress by improving course participants' knowledge, attitudes and behaviours
related to mental ill-health. The present paper aims to synthesize published
evaluations of the MHFA programme in a meta-analysis to estimate its effects and
potential as a public mental health awareness-increasing strategy. Fifteen
relevant papers were identified through a systematic literature search.
Standardized effect sizes were calculated for three different outcome measures:
change in knowledge, attitudes, and helping behaviours. The results of the meta
analysis for these outcomes yielded a mean effect size of Glass's Delta = 0.56
(95% CI = 0.38 - 0.74; p < 0.001), 0.28 (95% CI = 0.22 - 0.35; p < 0.001) and
0.25 (95% CI = 0.12 - 0.38; p < 0.001), respectively. Results were homogenous,
and moderator analyses suggested no systematic bias or differences in results
related to study design (with or without control group) or 'publication quality'
(journal impact factor). The results demonstrate that MHFA increases
participants' knowledge regarding mental health, decreases their negative
attitudes, and increases supportive behaviours toward individuals with mental
health problems. The MHFA programme appears recommendable for public health
action.
PMID- 25137114
TI - Social support network typologies and health outcomes of older people in low and
middle income countries--a 10/66 Dementia Research Group population-based study.
AB - This study aims to assess the construct validity of the Wenger social support
network typology in low and middle income countries. We hypothesize that, in
comparison with the integrated network type, the non-integrated network type is
associated with loneliness, depression, poor quality of life (less happiness),
poor self-reported health, increased disability and higher care needs. Cross
sectional one-phase surveys were conducted of all residents aged 65 and over in
catchment areas in eight low and middle income countries (India, China, Cuba,
Dominican Republic, Venezuela, Mexico, Peru and Puerto Rico). Wenger's
Practitioner Assessment of Network Type (PANT) was used to measure social network
type. Family dependent, local self-contained, wider community-focused and private
restricted network types were considered non-integrated, in comparison to the
locally integrated network type. Overall, 17,031 participants were interviewed.
Family dependent and locally integrated network types were the most prevalent.
Adjusted pooled estimates across sites showed that loneliness, depression, less
happiness, poor health, disability, and need for care were significantly
associated with non-integrated network type. The findings of this study support
the construct validity of Wenger's network typology in low and middle income
countries. However, further research is required to test the criterion validity
of Wenger typology using longitudinal data. Identifying older people who are
vulnerable could inform the development of social care interventions to support
older people and their families in the context of deteriorating health.
PMID- 25137115
TI - Eating disorders as a public health issue: prevalence and attributable impairment
of quality of life in an Italian community sample.
AB - The prevalence of eating disorders (ED) in the community is still under debate,
as well as the measure of their impact on the well-being of individuals. It was
decided to evaluate the prevalence of eating disorders in an Italian community
sample as well as to measure the burden of the quality of life of people and to
compare it to those attributable to other chronic illnesses. A community survey
of 4,999 people using a questionnaire on health services utilization, the
Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS), a semi
structured clinical interview derived from the non-patient version of the DSM-IV
(SCID/NP) and Short Form Health Survey (SF-12) was conducted. A total of 3,398
individuals were interviewed (68% of those recruited). Lifetime prevalence for
overall ED was 1.7%; for anorexia 0.7%; for bulimia 0.6% and for binge eating
disorder 0.5%. ED was more frequent in women than in men. No cases of anorexia in
men were identified. ED showed an attributable burden in impairing quality of
life with no statistically significant differences with those due to major
depressive disorder, bipolar spectrum disorders and Wilson's disease. Of the
pathological conditions considered, only multiple sclerosis showed a worsening
attributable burden. ED thus has a non-negligible frequency in Italy, with severe
impact on quality of life comparable to that produced by severe chronic
psychiatric and general medical conditions. These elements emphasize that ED is a
serious public health issue.
PMID- 25137116
TI - Preparation for parenthood programme: experiences from southern India.
AB - Parenting skills are critically important to ensure that children are brought up
in a safe environment. Recent evidence shows that studies of parenting skills are
still at a preliminary stage in low- and middle-income countries. These need to
involve family practitioners and religious groups who often play a major role in
preparing young people in India. There are organized programmes available in the
country for Christian adults to prepare themselves for marriage and family life
through various church initiatives and activities. In order to develop a
programme which can be used to prepare young parents for responsibilities of
parenthood, a needs assessment was carried out among 70 young adults who attended
a marriage preparation course in Bangalore, India. All the participants belonged
to the Christian faith. Participants consisted of 53% men and 47% women whose
average age for deciding to get married was 26.8 years. All of them expressed a
need for such a preparatory programme for parenthood. They considered they needed
to know about normal child development, behavioural management of children, to
develop adequate skills in handling children at different ages, and deal with
their own past issues with their own parents when they were being parented. The
results suggest that the development of a preparatory programme for young adults
to support them in the role of parenthood must take their views and needs into
account.
PMID- 25137117
TI - Psychological well-being of parents and family caregivers of children with
hearing impairment in south India: influence of behavioural problems in children
and social support.
AB - Parents of children with hearing impairment are at increased risk of mental
health morbidities. We examined the predictive factors associated with
caregiver's strain and psychological morbidities in parents and family caregivers
of children with hearing impairment. In total, n = 201 parents and family
caregivers of children with and without hearing impairment aged 3 to 16 years
were recruited. Caregiver's strain and psychological morbidities were measured
using the Zarit Burden scale and the World Health Organization's Self-Reporting
Questionnaire (SRQ-20). Presence of behavioural problems in children was measured
using the Strengths and Difficulties Questionnaire. After adjustment, low
educational attainment and domestic violence were found to be associated with
caregiving strain, whereas dissatisfaction with social support from family,
behavioural problems in children, and domestic violence strongly predicted
psychological morbidities. Addressing the mental healthcare needs of parents may
help in downsizing the impact of psychological morbidities on the well-being of
children with hearing impairment.
PMID- 25137118
TI - ICD-10 mental and behavioural disorders due to use of crack and powder cocaine as
treated at a public psychiatric emergency service: an analysis of visit
predictors.
AB - The present study investigated the predictors of an increased number of visits
from individuals with some of the diagnoses noted in chapter F14 of ICD-10, from
calls to the emergency psychiatric unit of a general hospital in Sao Paulo state,
Brazil, in the period 2011-2012. Poisson regression models were carried out for
the outcome variable, accounting for number of subsequent visits to the
psychiatric emergency unit. For the analysis of this outcome we took into account
the exposure time of each individual in the study. Our findings point to a
population at risk for frequent psychiatric emergency service visits: individuals
over 25 years. This population should be targeted for interventions on entry into
public healthcare due to increased psychiatric morbidity and greater clinical
morbidity already confirmed by previous studies. We discussed the need of these
individuals for special attention during the clinical or psychiatric emergency
consultation which, unfortunately, may be the access point for the public health
system. None of the other variables were related to the outcome of interest, such
as those related to the level of individual entry into the care network before
and after treatment, and other variables related to medical acts during the
visit.
PMID- 25137119
TI - Retention predictors of a smoking treatment provided by a public psychosocial
unit in Brazil.
AB - Psychosocial units in Brazil (CAPS) provide access to mental health and addiction
patients, who are not routinely treated for nicotine dependence. The present
study analysed predictors of retention of a 6-week treatment provided by a CAPS
unit to 367 smokers with a high rate of psychiatric disorders and addictions for
the period 2007-2010. Several baseline variables were collected. Retention was
defined as the presence of the individual in all four medical consultations and
six group sessions. Multivariate discrete time Cox survival regression models
were used to test for the outcome of interest. Timetables were used to explore in
which moment of the treatment each predictor was important. Time to smoking the
first cigarette (TTFC) 5 min or later after waking and nicotine patch use
(nicotine replacement therapy, NRT) were associated with retention. The present
study supports the importance of the variables TTFC and NRT when used in
treatment retention for a sample with a high rate of psychiatric and alcohol
disorders. NRT seems to be very important in the beginning of the treatment,
probably because of withdrawal symptoms. Individuals currently undergoing
psychiatric treatment and with alcohol problems had good retention rates
comparable to the other individuals.
PMID- 25137120
TI - The right to health in Paraguay.
AB - Access to facilities, services and opportunities designed to meet the needs of
health is a fundamental human right and is the key for people to enjoy other
human rights. However, in Paraguay, this right is still far from becoming
reality. The status of the country is the most disadvantaged when compared to the
average condition of the Mercosur (Argentina, Bolivia, Brazil, Paraguay, Uruguay
and Venezuela). Health, as a human right, expands as a social, economic, and
political matter. Inequality, poverty, exploitation, violence and injustice are
at the root of its poor quality and the consequent shortcomings that emerge from
it. Access to health in Paraguay must be further developed using a human rights
framework linking it with improving quality of life for all citizens. Such an
approach means that potentially powerful barriers and interests must be
questioned and contested wherever appropriate and that political and economic
priorities must change drastically.
PMID- 25137121
TI - The crisis in psychiatry: a public health perspective.
AB - The role and responsibilities of psychiatry and psychiatrists have changed
significantly in recent decades as a consequence of changes in society. The
target of psychiatrists has moved from the treatment of specific mental disorders
to the management of a wide range of psychological conditions. Following these
changes, a public health approach has been claimed as necessary for psychiatric
practice and research, given the current ongoing crisis in mental health. If we
want to promote a public health approach, the following actions should be
responsibly taken by modern mental health professionals: (1) the identification
of causes of mental disorders, (2) the refinement of diagnoses, (3) the social
inclusion of patients, (4) the involvement of users and carers in mental health
research and practice, and (5) the improvement of psychiatric treatments and
services. This crisis should represent a stimulus for all psychiatrists and a
reconceptualization of psychiatry as public health is not in question.
PMID- 25137125
TI - Effect of hydration on the kinetics of proton-bound dimer formation: experimental
and theoretical study.
AB - A kinetic study was performed on the proton-bound dimer formation of
cyclopentanone, cyclohexanone, and cycloheptanone at atmospheric pressure with
ion mobility spectrometry (IMS) at the temperature range of 30 to 70 degrees C.
Measured rate constants were in the range of 9.5 * 10(-11) to 4.5 * 10(-10) cm(3)
s(-1). Rate constants were also calculated using average dipole orientation (ADO)
theory employing density functional theory (DFT). Calculated rate constants were
in the range of 1.0-5.5 * 10(-9) cm(3) s(-1). The difference between experimental
and calculated rate constants was interpreted based on the hydration of the
protonated monomers so that water molecules were replaced with a neutral monomer
molecule in the process of dimer formation. This process requires activation
energy for the formation of dimer and consequently reduces the rate constants. To
verify our hypothesis, an effective rate constant (keff) was introduced, which
accounted for the energetically activated water-monomer replacement in the dimer
formation reactions. A good agreement was observed between the experimental rate
constants and calculated keff, confirming the validity of the proposed model in
explaining the kinetics of dimer formation in atmospheric pressure.
PMID- 25137126
TI - Interface engineering for CVD graphene: current status and progress.
AB - In the past decade, graphene and graphene-like 2D materials have drawn more and
more attention in both academia and industry due to their fascinating properties.
As an atomically thin 2D layered material, graphene has extremely high
environmental susceptibility, that is, its properties are strongly affected by
its surroundings. In this review, the current status and progress in graphene
interface engineering are systematically discussed, including the interface
between graphene (carbon sources) and an underlying growth substrate (catalyst),
the interface between graphene and a supporting layer during a transfer process,
as well as the interface between graphene and a modified substrate from the
viewpoint of device applications. These key techniques involved in graphene
synthesis, transfer, and device substrates can be further applied to other
related 2D layered materials such as MoS2 . Moreover, by combining 2D crystals in
one particular stack, 2D-based heterostructures with desired functionalities can
be achieved, which opens up a new avenue for the future applications of 2D
layered materials.
PMID- 25137123
TI - Spatio-temporal analyses of Symbiodinium physiology of the coral Pocillopora
verrucosa along large-scale nutrient and temperature gradients in the Red Sea.
AB - Algal symbionts (zooxanthellae, genus Symbiodinium) of scleractinian corals
respond strongly to temperature, nutrient and light changes. These factors vary
greatly along the north-south gradient in the Red Sea and include conditions,
which are outside of those typically considered optimal for coral growth.
Nevertheless, coral communities thrive throughout the Red Sea, suggesting that
zooxanthellae have successfully acclimatized or adapted to the harsh conditions
they experience particularly in the south (high temperatures and high nutrient
supply). As such, the Red Sea is a region, which may help to better understand
how zooxanthellae and their coral hosts successfully acclimatize or adapt to
environmental change (e.g. increased temperatures and localized eutrophication).
To gain further insight into the physiology of coral symbionts in the Red Sea, we
examined the abundance of dominant Symbiodinium types associated with the coral
Pocillopora verrucosa, and measured Symbiodinium physiological characteristics
(i.e. photosynthetic processes, cell density, pigmentation, and protein
composition) along the latitudinal gradient of the Red Sea in summer and winter.
Despite the strong environmental gradients from north to south, our results
demonstrate that Symbiodinium microadriaticum (type A1) was the predominant
species in P. verrucosa along the latitudinal gradient. Furthermore, measured
physiological characteristics were found to vary more with prevailing seasonal
environmental conditions than with region-specific differences, although the
measured environmental parameters displayed much higher spatial than temporal
variability. We conclude that our findings might present the result of long-term
acclimatization or adaptation of S. microadriaticum to regionally specific
conditions within the Red Sea. Of additional note, high nutrients in the South
correlated with high zooxanthellae density indicating a compensation for a
temperature-driven loss of photosynthetic performance, which may prove promising
for the resilience of these corals under increase of temperature increase and
eutrophication.
PMID- 25137128
TI - Three-dimensional titanium dioxide nanomaterials.
PMID- 25137124
TI - Bioinformatic indications that COPI- and clathrin-based transport systems are not
present in chloroplasts: an Arabidopsis model.
AB - Coated vesicle transport occurs in the cytosol of yeast, mammals and plants. It
consists of three different transport systems, the COPI, COPII and clathrin
coated vesicles (CCV), all of which participate in the transfer of proteins and
lipids between different cytosolic compartments. There are also indications that
chloroplasts have a vesicle transport system. Several putative chloroplast
localized proteins, including CPSAR1 and CPRabA5e with similarities to cytosolic
COPII transport-related proteins, were detected in previous experimental and
bioinformatics studies. These indications raised the hypothesis that a COPI-
and/or CCV-related system may be present in chloroplasts, in addition to a COPII
related system. To test this hypothesis we bioinformatically searched for
chloroplast proteins that may have similar functions to known cytosolic COPI and
CCV components in the model plants Arabidopsis thaliana and Oryza sativa (subsp.
japonica) (rice). We found 29 such proteins, based on domain similarity, in
Arabidopsis, and 14 in rice. However, many components could not be identified and
among the identified most have assigned roles that are not related to either COPI
or CCV transport. We conclude that COPII is probably the only active vesicle
system in chloroplasts, at least in the model plants. The evolutionary
implications of the findings are discussed.
PMID- 25137129
TI - Molecular dynamics simulations of tri-n-butyl-phosphate/n-dodecane mixture:
thermophysical properties and molecular structure.
AB - Molecular dynamics simulations of tri-n-butyl-phosphate (TBP)/n-dodecane mixture
in the liquid phase have been carried out using two recently developed TBP force
field models (J. Phys. Chem. B 2012, 116, 305) in combination with the all-atom
optimized potentials for liquid simulations (OPLS-AA) force field model for n
dodecane. Specifically, the electric dipole moment of TBP, mass density of the
mixture, and the excess volume of mixing were computed with TBP mole fraction
ranging from 0 to 1. It is found that the aforementioned force field models
accurately predict the mass density of the mixture in the entire mole fraction
range. Commensurate with experimental measurements, the electric dipole moment of
the TBP was found to slightly increase with the mole fraction of TBP in the
mixture. Also, in accord with experimental data, the excess volume of mixing is
positive in the entire mole fraction range, peaking at TBP mole fraction range
0.3-0.5. Finally, a close examination of the spatial pair correlation functions
between TBP molecules, and between TBP and n-dodecane molecules, revealed
formation of TBP dimers through self-association at close distance, a phenomenon
with ample experimental evidence.
PMID- 25137127
TI - Transcription, reverse transcription, and analysis of RNA containing artificial
genetic components.
AB - Expanding the synthetic biology of artificially expanded genetic information
systems (AEGIS) requires tools to make and analyze RNA molecules having added
nucleotide "letters". We report here the development of T7 RNA polymerase and
reverse transcriptase to catalyze transcription and reverse transcription of xNA
(DNA or RNA) having two complementary AEGIS nucleobases, 6-amino-5-nitropyridin-2
one (trivially, Z) and 2-aminoimidazo[1,2a]-1,3,5-triazin-4(8H)-one (trivially,
P). We also report MALDI mass spectrometry and HPLC-based analyses for oligomeric
GACUZP six-letter RNA and the use of ribonuclease (RNase) A and T1 RNase as
enzymatic tools for the sequence-specific degradation of GACUZP RNA. We then
applied these tools to analyze the GACUZP and GACTZP products of polymerases and
reverse transcriptases (respectively) made from DNA and RNA templates. In
addition to advancing this 6-letter AEGIS toward the biosynthesis of proteins
containing additional amino acids, these experiments provided new insights into
the biophysics of DNA.
PMID- 25137130
TI - Identification of phosphopeptides with unknown cleavage specificity by a de novo
sequencing assisted database search strategy.
AB - In theory, proteases with broad cleavage specificity could be applied to digest
protein samples to improve the phosphoproteomic analysis coverage. However, in
practice this approach is seldom employed. This is because the identification of
phosphopeptides without enzyme specificity by conventional database search
strategy is extremely difficult due to the huge search space. In this study, we
investigated the performance of a de novo sequencing assisted database search
strategy for the identification of such phosphopeptides. Firstly, we compared the
performance of conventional database search strategy and the de novo sequencing
assisted database search strategy for the identification of peptides and
phosphopeptides without stetting enzyme specificity. It was found that the
identification sensitivity dropped significantly for the conventional one while
it was only slightly decreased for the new approach. Then, this new search
strategy was applied to identify phosphopeptides generated by Proteinase K
digestion, which resulted in the identification of 717 phosphopeptides. Finally,
this strategy was utilized for the identification of serum endogenous
phosphopeptides, which were generated in vivo by different kinds of proteases and
kinases, and the identification of 68 unique serum endogenous phosphopepitdes was
successfully achieved.
PMID- 25137131
TI - Grape seed extract improves epithelial structure and suppresses inflammation in
ileum of IL-10-deficient mice.
AB - Defect in intestinal epithelial structure is a critical etiological factor of
several intestinal diseases such as inflammatory bowel disease. The objective of
this study was to evaluate the effect of grape seed extract (GSE), which contains
a mixture of polyphenols, on ileal mucosal structure and inflammation in
interleukin (IL)-10-deficient mice, a common model for studying inflammatory
bowel disease. Wild-type and IL-10-deficient mice were fed GSE at 0 or 1% (based
on dry feed weight) for 16 weeks. GSE supplementation decreased crypt depth and
increased (P < 0.05) the ratio of villus/crypt length in the terminal ileum.
Consistently, the dietary GSE decreased (P < 0.05) proliferation and enhanced (P
< 0.05) differentiation of epithelial cells. These changes in gut epithelium were
associated with the suppression of nuclear factor kappa-light-chain-enhancer of
activated B-cell (NF-kappaB) signaling. Furthermore, compared with WT mice, IL-10
deletion promoted beclin-1 and AMPK expression, both of which were decreased to
normal by GSE supplementation. These changes were associated with alterations in
epithelial barrier function as indicated by reduced pore forming claudin-2
protein expression and increased barrier forming claudin-1 protein expression in
the ileum of GSE supplemented mice. In summary, our data indicates that GSE
exerts protective effects to the ileal epithelial structure in IL-10-deficient
mice possibly through the suppression of inflammatory response.
PMID- 25137135
TI - Local coordination geometry perturbed beta-diketone dysprosium single-ion
magnets.
AB - A series of three beta-diketone mononuclear dysprosium complexes, namely,
Dy(TFI)3(H2O)2 (1), Dy(TFI)3(bpy) (2), and [Dy(TFI)3(Phen)].0.02CHCl3 (3) (TFI =
2-(2,2,2-trifluoroethyl)-1-indone, bpy = 2,2'-bipyridine, phen = 1,10
phenanthroline) have been designed and synthesized. Crystal structure analysis
reveals that complexes 1-3 have haveisomorphic structures in which the central
Dy(III) ion is eight-coordinated by six oxygen atoms from three TFI ligands and
two O/N atoms from auxiliary ligands, forming a distorted bicapped trigonal
prismatic geometry for 1, a distorted dodecahedral geometry for 2, and a
distorted square antiprismatic geometry for 3, respectively. Magnetic studies
indicate that complex 2 with D(2d) symmetry and 3 with D(4d) symmetry exhibit
slow magnetic relaxation with barrier heights (U(eff)/k(B)) of 48.8 K for 2 and
57.9 K for 3. Strikingly, the relaxation time (tau) of 0.0258 s for 3 is about 20
times that for 2, which is presumably associated with larger rotation of the SAP
surroundings for 3. Further, complexes 2 and 3 exhibit essential magnetic
hysteresis loops at 1.8 K. These extend the recent reports of the single-ion
magnets (SIMs) of beta-diketone mononuclear dysprosium complexes.
PMID- 25137134
TI - A novel reaction of peroxiredoxin 4 towards substrates in oxidative protein
folding.
AB - Peroxiredoxin 4 (Prx4) is the only endoplasmic reticulum localized peroxiredoxin.
It functions not only to eliminate peroxide but also to promote oxidative protein
folding via oxidizing protein disulfide isomerase (PDI). In Prx4-mediated
oxidative protein folding we discovered a new reaction that the sulfenic acid
form of Prx4 can directly react with thiols in folding substrates, resulting in
non-native disulfide cross-linking and aggregation. We also found that PDI can
inhibit this reaction by exerting its reductase and chaperone activities. This
discovery discloses an off-pathway reaction in the Prx4-mediated oxidative
protein folding and the quality control role of PDI.
PMID- 25137133
TI - Mitochondriome and cholangiocellular carcinoma.
AB - Cholangiocellular carcinoma (CCA) of the liver was the target of more interest,
recently, due mainly to its increased incidence and possible association to new
environmental factors. Somatic mitochondrial DNA (mtDNA) mutations have been
found in several cancers. Some of these malignancies contain changes of mtDNA,
which are not or, very rarely, found in the mtDNA databases. In terms of
evolutionary genetics and oncology, these data are extremely interesting and may
be considered a sign of poor fitness, which may conduct in some way to different
cellular processes, including carcinogenesis. MitoChip analysis is a strong tool
for investigations in experimental oncology and was carried out on three CCA cell
lines (HuCCT1, Huh-28 and OZ) with different outcome in human and a Papova
immortalized normal hepatocyte cell line (THLE-3). Real time quantitative PCR,
western blot analysis, transmission electron microscopy, confocal laser
microscopy, and metabolic assays including L-Lactate and NAD+/NADH assays were
meticulously used to identify mtDNA copy number, oxidative phosphorylation
(OXPHOS) content, ultrastructural morphology, mitochondrial membrane potential
(DeltaPsim), and differential composition of metabolites, respectively. Among 102
mtDNA changes observed in the CCA cell lines, 28 were non-synonymous coding
region alterations resulting in an amino acid change. Thirty-eight were
synonymous and 30 involved ribosomal RNA (rRNA) and transfer RNA (tRNA) regions.
We found three new heteroplasmic mutations in two CCA cell lines (HuCCT1 and Huh
28). Interestingly, mtDNA copy number was decreased in all three CCA cell lines,
while complexes I and III were decreased with depolarization of mitochondria. L
Lactate and NAD+/NADH assays were increased in all three CCA cell lines. MtDNA
alterations seem to be a common event in CCA. This is the first study using
MitoChip analysis with comprehensive metabolic studies in CCA cell lines
potentially creating a platform for future studies on the interactions between
normal and neoplastic cells.
PMID- 25137136
TI - Integrating multi-omics for uncovering the architecture of cross-talking pathways
in breast cancer.
AB - Cross-talk among abnormal pathways widely occurs in human cancer and generally
leads to insensitivity to cancer treatment. Moreover, alterations in the abnormal
pathways are not limited to single molecular level. Therefore, we proposed a
strategy that integrates a large number of biological sources at multiple levels
for systematic identification of cross-talk among risk pathways in cancer by
random walk on protein interaction network. We applied the method to multi-Omics
breast cancer data from The Cancer Genome Atlas (TCGA), including somatic
mutation, DNA copy number, DNA methylation and gene expression profiles. We
identified close cross-talk among many known cancer-related pathways with complex
change patterns. Furthermore, we identified key genes (linkers) bridging these
cross-talks and showed that these genes carried out consistent biological
functions with the linked cross-talking pathways. Through identification of
leader genes in each pathway, the architecture of cross-talking pathways was
built. Notably, we observed that linkers cooperated with leaders to form the
fundamentation of cross-talk of pathways which play core roles in deterioration
of breast cancer. As an example, we observed that KRAS showed a direct connection
to numerous cancer-related pathways, such as MAPK signaling pathway, suggesting
that it may be a central communication hub. In summary, we offer an effective way
to characterize complex cross-talk among disease pathways, which can be applied
to other diseases and provide useful information for the treatment of cancer.
PMID- 25137138
TI - Germination shifts of C3 and C4 species under simulated global warming scenario.
AB - Research efforts around the world have been increasingly devoted to investigating
changes in C3 and C4 species' abundance or distribution with global warming, as
they provide important insight into carbon fluxes and linked biogeochemical
cycles. However, changes in the early life stage (e.g. germination) of C3 and C4
species in response to global warming, particularly with respect to asymmetric
warming, have received less attention. We investigated germination percentage and
rate of C3 and C4 species under asymmetric (+3/+6 degrees C at day/night) and
symmetric warming (+5/+5 degrees C at day/night), simulated by alternating
temperatures. A thermal time model was used to calculate germination base
temperature and thermal time constant. Two additional alternating temperature
regimes were used to test temperature metrics effect. The germination percentage
and rate increased continuously for C4 species, but increased and then decreased
with temperature for C3 species under both symmetric and asymmetric warming.
Compared to asymmetric warming, symmetric warming significantly overestimated the
speed of germination percentage change with temperature for C4 species. Among the
temperature metrics (minimum, maximum, diurnal temperature range and average
temperature), maximum temperature was most correlated with germination of C4
species. Our results indicate that global warming may favour germination of C4
species, at least for the C4 species studied in this work. The divergent effects
of asymmetric and symmetric warming on plant germination also deserve more
attention in future studies.
PMID- 25137137
TI - A novel cell line derived from pleomorphic adenoma expresses MMP2, MMP9, TIMP1,
TIMP2, and shows numeric chromosomal anomalies.
AB - Pleomorphic adenoma is the most common salivary gland neoplasm, and it can be
locally invasive, despite its slow growth. This study aimed to establish a novel
cell line (AP-1) derived from a human pleomorphic adenoma sample to better
understand local invasiveness of this tumor. AP-1 cell line was characterized by
cell growth analysis, expression of epithelial and myoepithelial markers by
immunofluorescence, electron microscopy, 3D cell culture assays, cytogenetic
features and transcriptomic study. Expression of matrix metalloproteinases (MMPs)
and their tissue inhibitors (TIMPs) was also analyzed by immunofluorescence and
zymography. Furthermore, epithelial and myoepithelial markers, MMPs and TIMPs
were studied in the tumor that originated the cell line. AP-1 cells showed
neoplastic epithelial and myoepithelial markers, such as cytokeratins, vimentin,
S100 protein and smooth-muscle actin. These molecules were also found in vivo, in
the tumor that originated the cell line. MMPs and TIMPs were observed in vivo and
in AP-1 cells. Growth curve showed that AP-1 exhibited a doubling time of 3.342
days. AP-1 cells grown inside Matrigel recapitulated tumor architecture.
Different numerical and structural chromosomal anomalies were visualized in
cytogenetic analysis. Transcriptomic analysis addressed expression of 7 target
genes (VIM, TIMP2, MMP2, MMP9, TIMP1, ACTA2 e PLAG1). Results were compared to
transcriptomic profile of non-neoplastic salivary gland cells (HSG). Only MMP9
was not expressed in both libraries, and VIM was expressed solely in AP-1
library. The major difference regarding gene expression level between AP-1 and
HSG samples occurred for MMP2. This gene was 184 times more expressed in AP-1
cells. Our findings suggest that AP-1 cell line could be a useful model for
further studies on pleomorphic adenoma biology.
PMID- 25137139
TI - The CRISPR/Cas9 System Facilitates Clearance of the Intrahepatic HBV Templates In
Vivo.
AB - Persistence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA)
under current antiviral therapy is a major barrier to eradication of chronic
hepatitis B (CHB). Curing CHB will require novel strategies for specific
disruption of cccDNA. The clustered regularly interspaced short palindromic
repeats (CRISPR)/Cas9 system is a newly developed tool for site-specific cleavage
of DNA targets directed by a synthetic guide RNA (gRNA) base-paired to the target
DNA sequence. To examine whether this system can cleave HBV genomes, we designed
eight gRNAs against HBV of genotype A. With the HBV-specific gRNAs, the
CRISPR/Cas9 system significantly reduced the production of HBV core and surface
proteins in Huh-7 cells transfected with an HBV-expression vector. Among eight
screened gRNAs, two effective ones were identified. Interestingly, one gRNA
targeting the conserved HBV sequence acted against different genotypes. Using a
hydrodynamics-HBV persistence mouse model, we further demonstrated that this
system could cleave the intrahepatic HBV genome-containing plasmid and facilitate
its clearance in vivo, resulting in reduction of serum surface antigen levels.
These data suggest that the CRISPR/Cas9 system could disrupt the HBV-expressing
templates both in vitro and in vivo, indicating its potential in eradicating
persistent HBV infection.
PMID- 25137141
TI - Forensic interpretation of molecular variation on networks of disease
transmission and genetic inheritance.
AB - This paper describes the inference-on-networks (ION) framework for forensic
interpretat ION of molecular typing data in cases involving allegations of
infectious microbial transmission, association of disease outbreaks with alleged
sources, and identifying familial relationships using mitochondrial or Y
chromosomal DNA. The framework is applicable to molecular typing data obtained
using any technique, including those based on electrophoretic separations. A key
insight is that the networks associated with disease transmission or DNA
inheritance can be used to define specific testable relationships and avoid the
ambiguity and subjectivity associated with the criteria used for inferring
genetic relatedness now in use. We discuss specific applications of the framework
to the 2003 severe acute respiratory syndrome (SARS) outbreak in Singapore and
the 2001 foot-and-mouth disease virus (FMDV) outbreak in Great Britain.
PMID- 25137140
TI - The MicroRNA Biology of the Mammalian Nucleus.
AB - MicroRNAs (miRNAs) are a class of genome-encoded small RNAs that are primarily
considered to be post-transcriptional negative regulators of gene expression
acting in the cytoplasm. Over a decade of research has focused on this canonical
paradigm of miRNA function, with many success stories. Indeed, miRNAs have been
identified that act as master regulators of a myriad of cellular processes, and
many miRNAs are promising therapeutic targets or disease biomarkers. However, it
is becoming increasingly apparent that the canonical view of miRNA function is
incomplete. Several lines of evidence now point to additional functions for
miRNAs in the nucleus of the mammalian cell. The majority of cellular miRNAs are
present in both the nucleus and the cytoplasm, and certain miRNAs show specific
nuclear enrichment. Additionally, some miRNAs colocalize with sub-nuclear
structures such as the nucleolus and chromatin. Multiple components of the miRNA
processing machinery are present in the nuclear compartment and are shuttled back
and forth across the nuclear envelope. In the nucleus, miRNAs act to regulate the
stability of nuclear transcripts, induce epigenetic alterations that either
silence or activate transcription at specific gene promoters, and modulate
cotranscriptional alternative splicing events. Nuclear miRNA-directed gene
regulation constitutes a departure from the prevailing view of miRNA function and
as such, warrants detailed further investigation.
PMID- 25137143
TI - Lactase persistence and dairy intake in Mapuche and Mestizo populations from
southern Chile.
AB - Lactase persistence (LP) occurs at a very low frequency in indigenous populations
from Latin America, offering an opportunity to understand the relationship
between this genetic trait and patterns of dairy consumption. Here, the frequency
of LP is analyzed from Mapuche and -an adjacent- mestizo population inhabiting
the Araucania region. In addition to genotyping for LP, participants were
surveyed in relation to general perception and consumption habits of dairy
products. Low LP frequency (10%) and very low dairy intake was found among the
Mapuche population as compared with Mestizo populations inhabiting Chile. The
survey reported that the main reasons for avoidance of dairy were the
gastrointestinal symptoms after dairy intake and cultural dietary habits. The
interaction between low LP genotype frequency, low dairy intake, and
sociocultural determinants is here discussed in the light of their potential
health outcomes.
PMID- 25137142
TI - The cytoplasmic capping complex assembles on adapter protein nck1 bound to the
proline-rich C-terminus of Mammalian capping enzyme.
AB - Cytoplasmic capping is catalyzed by a complex that contains capping enzyme (CE)
and a kinase that converts RNA with a 5'-monophosphate end to a 5' diphosphate
for subsequent addition of guanylic acid (GMP). We identify the proline-rich C
terminus as a new domain of CE that is required for its participation in
cytoplasmic capping, and show the cytoplasmic capping complex assembles on Nck1,
an adapter protein with functions in translation and tyrosine kinase signaling.
Binding is specific to Nck1 and is independent of RNA. We show by sedimentation
and gel filtration that Nck1 and CE are together in a larger complex, that the
complex can assemble in vitro on recombinant Nck1, and Nck1 knockdown disrupts
the integrity of the complex. CE and the 5' kinase are juxtaposed by binding to
the adjacent domains of Nck1, and cap homeostasis is inhibited by Nck1 with
inactivating mutations in each of these domains. These results identify a new
domain of CE that is specific to its function in cytoplasmic capping, and a new
role for Nck1 in regulating gene expression through its role as the scaffold for
assembly of the cytoplasmic capping complex.
PMID- 25137144
TI - Percutaneous radiofrequency facet joint denervation with monitoring of compound
muscle action potential of the multifidus muscle group for treating chronic low
back pain: a preliminary report.
AB - STUDY DESIGN: A retrospective review. OBJECTIVE: The aim of this study was to
study the effectiveness of percutaneous radiofrequency neurotomy of facet joints
by monitoring compound muscle action potentials (CMAPs) of the multifidus muscle
group as an objective index of treatment efficacy. SUMMARY OF BACKGROUND:
Percutaneous radiofrequency neurotomy of the medial branches of the dorsal rami
of the lumbar nerves is a widely accepted treatment for chronic lumbar
intervertebral joint pain. However, its success rate has varied in different
studies because an objective method for evaluating the facet joint denervation is
lacking. METHODS: Fifty-five patients (age range, 19-76 y; mean age, 55 y) with
low back pain persisting for >=3 months, in whom facet block and/or block of the
medial branch of the dorsal ramus were only temporarily effective, were included.
The Japanese Orthopaedic Association (JOA) scoring system for back pain was used
for clinical assessment. JOA scores were measured before treatment and 1 week, 3
months, 6 months, and 12 months afterward. The improvement rate was calculated
with >=40% improvement rate defined as successful, and the success rate was
subsequently evaluated. RESULTS: The patient success rate was 75% (41/55) at 1
week, 71% (39/55) at 3 months, 60% (33/55) at 6 months, and 51% (28/55) at 12
months after treatment. Two cases had minor postoperative complications, which
were localized burning pain lasting <1 week at the site of electrode insertion.
CONCLUSIONS: Our results suggest that percutaneous radiofrequency facet joint
denervation with CMAPs monitoring is a safe, long-lasting, and effective
treatment for chronic facet joint pain. CMAP monitoring may be useful as an
objective index for facet denervation.
PMID- 25137146
TI - Reduced Endotracheal Tube Cuff Pressure to Assess Dysphagia After Anterior
Cervical Spine Surgery.
AB - STUDY DESIGN: This was a prospective, randomized control pilot study. OBJECTIVE:
The aim of this study was to determine whether continuous monitoring and
adjustment of the endotracheal tube cuff pressure (ETTCP) to 15 mm Hg during ACSS
would alter the incidence of postoperative dysphagia. SUMMARY OF BACKGROUND DATA:
Postoperative dysphagia is a recognized potential complication of anterior
cervical spine surgery (ACSS). Recent findings on preventive measures suggest
that certain intraoperative practices may minimize this complication. METHODS:
Fifty patients undergoing ACSS, arthroplasty, or fusion, completed routine
lateral cervical preoperative plain films and questionnaires [Dysphagia
Disability Index (DDI), Bazaz-Yoo Dysphagia Score (BYDS), and Short Form (36)
Health Survey]. Patients were randomized into 2 groups: treatment group with
ETTCP maintained at 15 mm Hg and control group with cuff pressure monitored
without manipulation. Radiographs and questionnaires were obtained at 24 hours, 6
weeks, and 3 and 6 months postsurgery to assess soft tissue thickness and rates
of dysphagia. RESULTS: There were no significant differences between the groups
in the soft tissue thickness or questionnaire scores at any timepoint (P>0.05).
Within-group analysis revealed treatment and control groups had a significantly
higher 24-hour postoperative soft tissue thickness and questionnaire scores
compared with follow-up measurements (P<0.05). In the pooled group (n=50), the 24
hour postoperative DDI, BYDS, and soft tissue thickness were significantly higher
compared with all other timepoints (P<0.01). DDI scores >=10 related to dysphagia
were in 59% of patients at 24 hours, 35% at 6 weeks, 24% at 3 months, and 18% at
6 months. CONCLUSIONS: This study suggests decreased ETTCP has no effect on the
prevalence of dysphagia. The incidence of dysphagia decreases over time and
normalizes by 6 months postsurgery.
PMID- 25137145
TI - Surgical treatment of large abdominally involved primary dumbbell tumor in the
lumbar region.
AB - STUDY DESIGN: This was a retrospective clinical study. OBJECTIVE: The aim of this
study was to assess the efficacy of a combined anterior and posterior approach,
or single-stage posterior extensive approach for resection of large abdominally
involved dumbbell tumor in the lumbar region. BACKGROUND: Resection of the large
spinal-retroperitoneal involved dumbbell tumor is particularly controversial and
challenging because of unique exposure requirements. METHODS: From June 2006 to
October 2011, 18 consecutive patients suffering from large dumbbell tumors in the
lumbar region were involved. In the initial 8 patients, a combined posterior and
anterior surgical approach was applied. The remaining 10 patients were surgically
treated with a single posterior extensive approach to excise both the intraspinal
and intra-abdominal tumors. Reconstruction with bone or mesh grafts was also
performed simultaneously in 3 of the 10 patients in this group. RESULTS: The
perioperative period was uneventful for 7 of 8 patients who underwent combined
surgery. However, 1 patient encountered right nephrectomy because of a ruptured
renal vein and refractory bleeding during anterior tumor exposure. Histopathology
revealed the presence of schwannoma (n=4), neurofibroma (n=3), and neuroblastoma
(n=1). With the mean of 52 months of follow-up, metastasis occurred in 1 patient
with neuroblastoma. In the 10 patients with only the posterior approach,
histopathology demonstrated schwannoma (n=5), neurofibroma (n=3), small round
cell mesenchymal tumor (n=1), and benign fibrous histiocytoma (n=1). No
recurrence was detected at the mean follow-up of 24 months. CONCLUSIONS: The
posterior extensive approach is safe and effective to remove the large
abdominally involved dumbbell tumors, and also facilitates simultaneously
reconstruction of the vertebral body, as compared with the combined posterior and
anterior approach.
PMID- 25137147
TI - The Reliabilities of Radiographic Measurements of Cervical Sagittal Alignment in
Ankylosing Spondylitis.
AB - STUDY DESIGN: This is a prospective study design. OBJECTIVE: To test the
interobserver and intraobserver reliabilities of 5 specific measures of global
cervical sagittal alignment in patients with ankylosing spondylitis (AS), and to
suggest a better means of measuring cervical sagittal alignment. SUMMARY OF
BACKGROUND DATA: The intraobserver and interobserver reliabilities of several
different methods of measuring cervical lordosis have been reported. However,
they have not been studied till yet in patients with AS. METHODS: Interobserver
and intraobserver reliabilities of 5 specific measures of cervical lordosis were
evaluated in patients with AS. Eighty patients with AS were allocated to a
nonankylosis or an ankylosis group, and the reliabilities of the Cobb C1-C7, Cobb
C2-C7, centroid, posterior tangent, and Ishihara index methods were evaluated.
RESULTS: The intraclass and interclass correlation coefficients (ICCs) of all 5
methods were generally high. For the 80 study subjects, ICCs were >=0.84
(excellent) for all 5 radiographic methods. However, comparison of the ICCs, 95%
confidence intervals, and mean absolute differences (MAD) between groups with
varying degrees of ankylosis showed that the reliability of lordosis measurements
decreased as the severity of ankylosis increased. The 5 methods consistently
demonstrated higher ICCs for both interobserver and intraobserver comparisons in
the nonankylosis group. However, in the ankylosis group, the Cobb C1-C7 method
demonstrated high ICCs for both interobserver and intraobserver comparisons,
whereas the other 4 methods had high ICCs only for intraobserver comparisons. The
intraobserver MADs were similar for the 5 methods (2.4-3.9), but the
interobserver MADs of measurement methods in both groups showed low measurement
reliability except for the Cobb C1-C7 methods. CONCLUSIONS: This study provides a
reliability analysis of different cervical lordosis measurement methods in AS,
and shows that the Cobb C1-C7 method provides a reliable means for measuring
cervical lordosis in AS.
PMID- 25137149
TI - Synthesis of a poly-hydroxypyrolidine-based inhibitor of Mycobacterium
tuberculosis GlgE.
AB - Long treatment times, poor drug compliance, and natural selection during
treatment of Mycobacterium tuberculosis (Mtb) have given rise to extensively drug
resistant tuberculosis (XDR-TB). As a result, there is a need to identify new
antituberculosis drug targets. Mtb GlgE is a maltosyl transferase involved in
alpha-glucan biosynthesis. Mutation of GlgE in Mtb increases the concentration of
maltose-1-phosphate (M1P), one substrate for GlgE, causing rapid cell death. We
have designed 2,5-dideoxy-3-O-alpha-d-glucopyranosyl-2,5-imino-d-mannitol (9) to
act as an inhibitor of GlgE. Compound 9 was synthesized using a convergent
synthesis by coupling thioglycosyl donor 14 and 5-azido-3-O-benzyl-5-deoxy-1,2-O
isopropylidene-beta-d-fructopyranose (23) to form disaccharide 24. A reduction
and intramolecular reductive amination transformed the intermediate disaccharide
24 to the desired pyrolidine 9. Compound 9 inhibited both Mtb GlgE and a variant
of Streptomyces coelicolor (Sco) GlgEI with Ki = 237 +/- 27 MUM and Ki = 102 +/-
7.52 MUM, respectively. The results confirm that a Sco GlgE-V279S variant can be
used as a model for Mtb GlgE. In conclusion, we designed a lead transition state
inhibitor of GlgE, which will be instrumental in further elucidation of the
enzymatic mechanism of Mtb GlgE.
PMID- 25137150
TI - SDF-1alpha stiffens myeloma bone marrow mesenchymal stromal cells through the
activation of RhoA-ROCK-Myosin II.
AB - Multiple myeloma (MM) is a B lymphocyte malignancy that remains incurable despite
extensive research efforts. This is due, in part, to frequent disease recurrences
associated with the persistence of myeloma cancer stem cells (mCSCs). Bone marrow
mesenchymal stromal cells (BMSCs) play critical roles in supporting mCSCs through
genetic or biochemical alterations. Previously, we identified mechanical
distinctions between BMSCs isolated from MM patients (mBMSCs) and those present
in the BM of healthy individuals (nBMSCs). These properties of mBMSC contributed
to their ability to preferentially support mCSCs. To further illustrate
mechanisms underlying the differences between mBMSCs and nBMSCs, here we report
that (i) mBMSCs express an abnormal, constitutively high level of phosphorylated
Myosin II, which leads to stiffer membrane mechanics, (ii) mBMSCs are more
sensitive to SDF-1alpha-induced activation of MYL2 through the G(i./o)-PI3K-RhoA
ROCK-Myosin II signaling pathway, affecting Young's modulus in BMSCs and (iii)
activated Myosin II confers increased cell contractile potential, leading to
enhanced collagen matrix remodeling and promoting the cell-cell interaction
between mCSCs and mBMSCs. Together, our findings suggest that interfering with
SDF-1alpha signaling may serve as a new therapeutic approach for eliminating
mCSCs by disrupting their interaction with mBMSCs.
PMID- 25137152
TI - A longer diagnostic interval is a risk for depression in amyotrophic lateral
sclerosis.
AB - OBJECTIVE: Recognizing depressive symptoms in patients with amyotrophic lateral
sclerosis (ALS) remains problematic given the potential overlap with the normal
psychological responses to a terminal illness. Understanding mental health and
disease-related risk factors for depression is key to identifying psychological
morbidity. The present study aimed to determine the prevalence of depressive
symptoms in ALS and to explore mental health and disease-related risk factors for
depression. METHOD: Structured medical and psychiatric history questionnaires and
a validated depression scale (Depression, Anxiety, Stress Scale-21) were
completed by 27 ALS patients (60% female; 59% limb onset; age 65.11 +/- SE 2.21)
prior to their initial review at a multidisciplinary clinic. Physical function
was assessed with the Amyotrophic Lateral Sclerosis Functional Rating Scale
(ALSFRS-R). RESULTS: At the time of initial assessment, 44% of patients had a
previous psychiatric history, although the majority (62%) reported no symptoms of
depression. The mean ALSFRS-R score was 37.78 +/- SE 1.22, with an average
diagnostic interval of 16.04 +/- SE 2.39 months. Logistic regression analysis
revealed that the length of the diagnostic interval alone predicted depressive
symptoms (chi2(3, n = 26) = 9.21, Odds Ratio (OR) = 1.12, p < 0.05. SIGNIFICANCE
OF RESULTS: The illness experiences of ALS patients rather than established
mental health risk factors influence the manifestation of depressive symptoms in
the early stages of the disease, with clinical implications for the assessment
and treatment of psychological morbidity. Patients with lengthy diagnostic
intervals may be prime targets for psychological assessment and intervention,
especially in the absence of ALS-specific tests and biomarkers.
PMID- 25137151
TI - Osteogenic gene transcription is regulated via gap junction-mediated cell-cell
communication.
AB - An analytical study of cell-cell communications between murine osteoblast-like
MLO-A5 cells and bone marrow mesenchymal stem cell (BMSC)-like C3H10T1/2 cells
was performed. C3H10T1/2 cells expressing green fluorescent protein (10T-GFP
cells) were generated to enable the isolation of the BMSC-like cells from co
cultures with MLO-A5 cells. The mRNA expression levels of several osteogenic
transcription factors (Runx2, Osterix, Dlx5, and Msx2) did not differ between the
co-cultured and mono-cultured 10T-GFP cells, but those of alkaline phosphatase
(ALP) and bone sialoprotein (BSP) were 300- to 400-fold higher in the co-cultured
cells. Patch clamp and biocytin transfer assays revealed gap junction-mediated
communication between co-cultured 10T-GFP and MLO-A5 cells. The addition of a gap
junction inhibitor suppressed the increases in the expression levels of the ALP
and BSP mRNAs in co-cultured 10T-GFP cells. Furthermore, the histone acetylation
levels were higher in co-cultured 10T-GFP cells than in mono-cultured 10T-GFP
cells. These results suggest that osteoblasts and BMSCs associate via gap
junctions, and that gap junction-mediated signaling induces histone acetylation
that leads to elevated transcription of the genes encoding ALP and BSP in BMSCs.
PMID- 25137155
TI - Application of empirical wave run-up formulas to the Polish Baltic Sea coast.
AB - Advanced, multidimensional models are typically applied when researching
processes occurring in the nearshore. Relatively simple, empirical equations are
commonly used in coastal engineering practice in order to estimate extreme wave
run-up on beaches and coastal structures. However, they were mostly calibrated to
the characteristics of oceanic coasts, which have different wave regime than a
semi-enclosed basin like the Baltic Sea. In this paper we apply the formulas to
the Polish Baltic Sea coast. The equations were adjusted to match local
conditions in two test sites in Miedzyzdroje and Dziwnowek, where beaches are
under continuous video surveillance. Data from WAM wave model and coastal gauge
stations were used, as well as precise measurements of the beaches' cross
sections. More than 600 run-up events spanning from June to December 2013 were
analysed, including surges causing dune erosion. Extreme wave run-up R2% was
calculated and presented as a percentage value indicating what part of the beach
was inundated. The method had a root-mean-square error of 6.1 and 6.5 percentage
points depending on the test site. We consider it is a fast and computationally
undemanding alternative to morphodynamic models. It will constitute a part of the
SatBaltyk Operating System-Shores, delivering forecasts of wave run-up on the
beaches for the entire Polish coastline.
PMID- 25137153
TI - Molecular analysis of Aedes aegypti classical protein tyrosine phosphatases
uncovers an ortholog of mammalian PTP-1B implicated in the control of egg
production in mosquitoes.
AB - BACKGROUND: Protein Tyrosine Phosphatases (PTPs) are enzymes that catalyze
phosphotyrosine dephosphorylation and modulate cell differentiation, growth and
metabolism. In mammals, PTPs play a key role in the modulation of canonical
pathways involved in metabolism and immunity. PTP1B is the prototype member of
classical PTPs and a major target for treating human diseases, such as cancer,
obesity and diabetes. These signaling enzymes are, hence, targets of a wide array
of inhibitors. Anautogenous mosquitoes rely on blood meals to lay eggs and are
vectors of the most prevalent human diseases. Identifying the mosquito ortholog
of PTP1B and determining its involvement in egg production is, therefore,
important in the search for a novel and crucial target for vector control.
METHODOLOGY/PRINCIPAL FINDINGS: We conducted an analysis to identify the ortholog
of mammalian PTP1B in the Aedes aegypti genome. We identified eight genes coding
for classical PTPs. In silico structural and functional analyses of proteins
coded by such genes revealed that four of these code for catalytically active
enzymes. Among the four genes coding for active PTPs, AAEL001919 exhibits the
greatest degree of homology with the mammalian PTP1B. Next, we evaluated the role
of this enzyme in egg formation. Blood feeding largely affects AAEL001919
expression, especially in the fat body and ovaries. These tissues are critically
involved in the synthesis and storage of vitellogenin, the major yolk protein.
Including the classical PTP inhibitor sodium orthovanadate or the PTP substrate
DiFMUP in the blood meal decreased vitellogenin synthesis and egg production.
Similarly, silencing AAEL001919 using RNA interference (RNAi) assays resulted in
30% suppression of egg production. CONCLUSIONS/SIGNIFICANCE: The data reported
herein implicate, for the first time, a gene that codes for a classical PTP in
mosquito egg formation. These findings raise the possibility that this class of
enzymes may be used as novel targets to block egg formation in mosquitoes.
PMID- 25137154
TI - Transmission of epi-alleles with MET1-dependent dense methylation in Arabidopsis
thaliana.
AB - DNA methylation in plants targets cytosines in three sequence contexts, CG, CHG
and CHH (H representing A, C or T). Each of these patterns has traditionally been
associated with distinct DNA methylation pathways with CHH methylation being
controlled by the RNA dependent DNA methylation (RdDM) pathway employing small
RNAs as a guide for the de novo DOMAINS REARRANGED METHYLTRANSFERASE (DRM2), and
maintenance DNA METHYLTRANSFERASE1 (MET1) being responsible for faithful
propagation of CG methylation. Here we report an unusual 'dense methylation'
pattern under the control of MET1, with methylation in all three sequence
contexts. We identified epi-alleles of dense methylation at a non coding RNA
locus (At4g15242) in Arabidopsis ecotypes, with distinct dense methylation and
expression characteristics, which are stably maintained and transmitted in
genetic crosses and which can be heritably altered by depletion of MET1. This
suggests that, in addition to its classical CG maintenance function, at certain
loci MET1 plays a role in creating transcriptional diversity based on the
generation of independent epi-alleles. Database inspection identified several
other loci with MET1-dependent dense methylation patterns. Arabidopsis ecotypes
contain distinct epi-alleles of these loci with expression patterns that
inversely correlate with methylation density, predominantly within the
transcribed region. In Arabidopsis, dense methylation appears to be an exception
as it is only found at a small number of loci. Its presence does, however,
highlight the potential for MET1 as a contributor to epigenetic diversity, and it
will be interesting to investigate the representation of dense methylation in
other plant species.
PMID- 25137156
TI - Stereoselective synthesis of C-fused pyranoindoles, pyranobenzofurans and
pyranobenzothiophene scaffolds using oxa-Pictet-Spengler type reaction of
vinylogous carbonates.
AB - C-fused pyranoheterocycles can be readily assembled using an intramolecular oxa
Pictet-Spengler type reaction of vinylogous carbonates in a highly
stereoselective manner. Required indole and benzofuran rings tethered to
vinylogous carbonates are prepared by a tandem Sonogashira coupling
nucleopalladation reaction. The entire process can also be carried out in a 'one
pot' manner starting from homopropargyl alcohol. The C-fused pyranoindoles could
be converted to spirooxindoles as well as to ring expanded products under
oxidative conditions.
PMID- 25137157
TI - Underestimated potential of organometallic rhenium complexes as anticancer
agents.
AB - In the recent years, organometallic compounds have become recognized as promising
anti-cancer drug candidates. While radioactive (186/188)Re compounds are already
used in clinics for cancer treatment, cold Re organometallic compounds have
mostly been explored as luminescent probes for cell imaging and photosensitizers
in photocatalysis. However, a growing number of studies have recently revealed
the potential of Re organometallic complexes as anti-cancer agents. Several
compounds have displayed cytotoxicity equaling or exceeding that of the well
established anti-cancer drug cisplatin. In this review, we present the currently
known Re organometallic complexes that have shown anti-proliferative activity on
cancer cell lines. A particular emphasis is placed on their cellular uptake and
localization as well as their potential mechanism of action.
PMID- 25137158
TI - [Cost-minimization analysis of subcutaneous abatacept in the treatment of
rheumatoid arthritis in Spain].
AB - OBJECTIVE: To compare the cost of treating rheumatoid arthritis patients that
have failed an initial treatment with methotrexate, with subcutaneous abatacept
versus other first-line biologic disease-modifying antirheumatic drugs. METHOD:
Subcutaneous abatacept was considered comparable to intravenous abatacept,
adalimumab, certolizumab pegol, etanercept, golimumab, infliximab and
tocilizumab, based on indirect comparison using mixed treatment analysis. A cost
minimization analysis was therefore considered appropriate. The Spanish Health
System perspective and a 3 year time horizon were selected. Pharmaceutical and
administration costs (Euros 2013) of all available first-line biological disease
modifying antirheumatic drugs were considered. Administration costs were obtained
from a local costs database. Patients were considered to have a weight of 70 kg.
A 3% annual discount rate was applied. Deterministic and probabilistic
sensitivity analyses were performed. RESULTS: Subcutaneous abatacept proved in
the base case to be less costly than all other biologic antirrheumatic drugs
(ranging from Euros -831.42 to Euros -9,741.69 versus infliximab and tocilizumab,
respectively). Subcutaneous abatacept was associated with a cost of Euros
10,760.41 per patient during the first year of treatment and Euros 10,261.29 in
subsequent years. The total 3-year cost of subcutaneous abatacept was Euros
29,953.89 per patient. Sensitivity analyses proved the model to be robust.
Subcutaneous abatacept remained cost-saving in 100% of probabilistic sensitivity
analysis simulations versus adalimumab, certolizumab, etanercept and golimumab,
in more than 99.6% versus intravenous abatacept and tocilizumab and in 62.3%
versus infliximab. CONCLUSIONS: Treatment with subcutaneous abatacept is cost
saving versus intravenous abatacept, adalimumab, certolizumab, etanercept,
golimumab, infliximab and tocilizumab in the management of rheumatoid arthritis
patients initiating treatment with biological antirheumatic drugs.
PMID- 25137159
TI - [Long-term cost-effectiveness of ticagrelor versus clopidogrel in acute coronary
syndrome in Spain].
AB - OBJECTIVE: To assess the cost-effectiveness relationship of Ticagrelor versus
Clopidogrel for the management of acute coronary syndrome in Spain. METHODS: The
data from the PLATO study were used for the calculation of the events rate and
health-related quality of life for Ticagrelor and Clopidogrel for the first 12
months, whereas the costs were obtained from Spanish sources. Quality of life
adjusted survival and costs were estimated according to the fact that the
patients did not suffer any thrombotic event (myocardial infarction or ictus) or
this one was not fatal. The lifetime cots, life years gained, and the quality of
life-adjusted survival were estimated for both treatment arms. Incremental cost
effectiveness ratios were assessed through the perspective of the Spanish
healthcare system for 2013, by using a macro-costs strategy based on published
literature and the survival tables for the Spanish population. RESULTS: Treatment
with Ticagrelor was associated to an incremental cost of 1,228 Euros per year, an
increase in 0.1652 life years gained, and 0.1365 years adjusted by quality of
life, as compared to Clopidogrel. The cost for one quality of life-adjusted life
year was 8,997 Euros and the cost per one gained life year of 7,435 ?. The
sensitivity analysis showed consistent results. CONCLUSIONS: Treatment of acute
coronary syndrome for 12 months with Ticagrelor was associated with a cost per 1
life year of quality of life-adjusted cost below the cost-effectiveness limits
generally accepted in Spain.
PMID- 25137160
TI - [Intravenous drugs infusion safety through smart pumps].
AB - OBJECTIVE: To analyze the role of smart infusion pumps in reducing errors related
with the administration of intravenous medications. METHOD: Retrospective,
observational study analyzing the implementation of a system with smart
intravenous infusion pumps (Hospira MedNetTM) and the role of the safety system
for the detection of errors during the administration of drugs, sera, and blood.
We included infusions administered at the day-care hospitals of hematology,
oncology, rheumatology, and oncopediatrics. We analyzed adherence to the safety
system, the number of programming errors detected, the commonly implicated drugs
in these errors, and improvement actions. RESULTS: During the study period, 120
smart pumps were implemented and data on 70,028 infusions were gathered. The rate
of adherence to the safety program was 62.30% in hematology (6,887 infusions),
60,30% in oncology (28,127 infusions), 46,50% in rheumatology (1,950 infusions)
and 1.8% in oncopediatrics (139 infusions). 3,481 out of the established limits
programming alerts were generated by the pumps: 2,716 of relative limit and 765
of absolute limit. En 807 infusions (2.17%), errors that could have had
consequences for the patients could be prevented. These findings allowed
implementing a series of strategies aimed at minimizing these errors in the
future. CONCLUSIONS: The Hospira MedNetTM system detects deviations from the
established protocols of intravenous infusion, preventing in this way potential
adverse events for the patients. It also allows establishing correction measures
and implementing the improvement strategies.
PMID- 25137161
TI - [Validation of genetic polymorphisms associated to the toxicity of chemotherapy
in colorectal cancer patients].
AB - OBJECTIVE: To validate the associations previously found in three cohorts of
patients from the General University Hospital Gregorio Maranon, between the
polymorphisms rs1128503, rs2032582 and rs1045642 of the ABCB1 gene and the hand
foot syndrome and diarrhea in colorectal cancer patients treated with
chemotherapy regimes containing Capecitabine and 5-Fluorouracil, respectively,
and between the polymorphisms rs2297595 of the DPYD gene and nausea/vomiting,
rs11615 of ERCC1 and neutropenia, and rs28399433 CYP2A6 and neutropenia, in
colorectal cancer patients treated with FOLFOX or XELOX as adjuvant therapy.
METHOD: Colorectal cancer patients treated with chemotherapy regimes, containing
Capecitabine (n = 157), 5-Fluorouracil (n = 99) were included in the study, as
well as patients treated with XELOX or FOLFOX (n = 83) as adjuvant therapy. The
patients included were recruited from the Doce de Octubre University Hospital and
from the Gregorio Maranon General University Hospital, and signed the informed
consent form. DNA was obtained from blood samples. Genotyping was carried out
with SNaPshot. Contingency tables were created for analyzing the associations
between the genotypes and the adverse reactions. RESULTS: None of the
associations previously identified was replicated in the validation cohort.
CONCLUSIONS: Pharmacogenetic studies with a limited sample size must be validated
with bigger cohorts, if possible by means of multicentre studies, reducing the
variables to the maximum and should never be used in clinical practice without
validation.
PMID- 25137162
TI - [Adherence, satisfaction and health-related quality of life in HIV-infected
patients with antiretroviral therapy in Spain. The ARPAS study].
AB - OBJECTIVE: To determine the relationship between satisfaction with antiretroviral
therapy (ART), adherence and quality of life (QoL) in adult patients diagnosed
with HIV infection and ART according to the posologic load. METHOD: Multicenter,
observational and cross-sectional study. Socio-demographic, clinical and of
posologic load (1, 2-4 or > 4 tablets/day), adherence (SMAQ, dispensation
recordings (DR) and visual analogical scale), satisfaction (ESART questionnaire)
and QoL (MOS-HIV) variables were gathered. An adherent patient was defined as the
one presenting simultaneously adherence according to SMAQ and DR > 95%. RESULTS:
328 patients (76% men; 46.0 +/- 9.2 years) were evaluated. The posology of 1
tablet/day, 2-4 tablets/day and > 4 tablets/day occurred in 29%, 37% and 34% of
the patients, respectively. Although the evaluation performed through the SMAQ
questionnaire and the VAS scale independently showed statistically significant
differences in favor of the 1 tablet/day scheme, the percentage (49%) of adherent
patients according to the combined variable did not differ between the groups
based on the posologic load. The satisfaction with ART and QoL were high in the
three groups, being the 1 tablet/day scheme the one related with higher
satisfaction and lower rate of adverse effects on fat metabolism. There were no
differences in patients' satisfaction by the adherence level. CONCLUSIONS:
Adherence, satisfaction with ART and QoL of the patients with ART are high.
Although higher in patients taking 1 tablet/day, the satisfaction did not differ
according to the level of adherence and no correlation was observed between
satisfaction with ART and quality of life.
PMID- 25137163
TI - [Analysis of ocular toxicity of fluconazole and voriconazole eyedrops using HET
CAM].
AB - PURPOSE: The objective of the study is to provide toxicological information
through the HET-CAM test of Fluconazole and Voriconazole eye drops prepared
commonly in Pharmacy Services for the treatment of fungal keratitis. METHOD:
Experimental Study. The ocular toxicity of topical voriconazole 10 mg/ml and
fluconazole 2 mg/ml were evaluated by the hen's egg test (HET) on the
chorioallantoic membrane (CAM). The effects on blood vessels were based on its
behavior during 300 seconds and processes that may occur at each time, then we
calculated the irritation index (is, irritation score). RESULTS AND CONCLUSIONS:
Both eye drops, voriconazol and fluconazole have been proven to be safe, since
the IS that we obtained was zero for both samples and did not present significant
signs of irritation. Therefore, these eyedrops are considered suitable for ocular
use from a toxicological point of view.
PMID- 25137164
TI - [Prevalence of potentially inappropriate medication in hospitalized elderly
patients by using explicit criteria].
AB - INTRODUCTION: Potentially inappropriate medication (PIM) prescribing in older
adults is quite prevalent and is associated with an increased risk for adverse
drug events, morbidity, and utilization of health care resources. The aim of this
study was to determine the prevalence and type of PIM in polypharmacy elderly
patients on admission and discharge and the factors associated with their
prescription. Just as the applicability of various explicit criteria selected
from the literature and adapted to our area. METHODS: We performed a cross
sectional study for 12 months (March 2010-February 2011) on 179 polypharmacy
elderly patients admitted to an Internal Medicine Department. We created a list
of 50 PIM using a Delphi approach based on previous published criteria (Beers,
Stopp, BMC and Priscus). Through patient interviews, review of medical records
and discharge reconciliation report, we identified the prevalence of PIM in the
patients. We also analyzed the relationship between different factors and the
prescription of PIM. RESULTS: The prevalence of patients with PIM on admission
and discharge were 71% and 48%, respectively. Out of the 50 selected PIM, 27 and
26 were detected on admission and discharge, respectively (55.5% and 57.69%
included on STOPP criteria). We detected two factors associated with PIM
prescription at discharge: severe-total dependence (OR = 1.8) and prescription of
more than 11 drugs (OR = 2). CONCLUSIONS: PIM prevalence in our population is
very high (70%), especially at hospital admission. These findings support the
need for measures aimed at improving the quality of prescriptions, especially on
dependent patients with polypharmacy.
PMID- 25137166
TI - Medication non-adherence as a cause of hospital admissions.
AB - OBJECTIVES: 1. To determine the profile of patients who are admitted to hospital
as a result of non-adherence. 2. To obtain an estimate of the economic impact for
the hospital. METHODS: Observational and retrospective study that included
patients who were admitted to hospital with a secondary diagnosis of "Personal
history of non-compliance with chronic medication" according to International
Classification of Diseases, during 2012. DATA COLLECTED: demographics;
socioeconomic and clinical data; data related to the treatment; readmissions;
hospital days; degree of adherence: <= 75% or severe non-adherence and > 75% or
moderate non-adherence; type of non-adherence: non-persistence and noncompliance;
hospitalization costs. Statistical analysis was performed. RESULTS: Eighty-seven
patients were admitted. These patients caused 104 episodes (16.3% were
readmissions). 71.2% were men, and 51.5 (SD 17.8) years old. All patients had a
chronic disease, adherence <= 75% (76%) and non-persistence (63.5%). Polypharmacy
(47.1%) was not associated with non-adherence. Total stay was 1,527 days (mean
stay was 14.7 (SD 14.0) days/episode): psychiatry 827 days (54.2%); cardiology
174 days (11.4%); critical unit 48 days (3.1%). Patients with a degree of
adherence <= 75% had a mean stay/episode higher than those with a degree of
adherence > 75%, without significant differences (p > 0.05, t-Student). Overall
cost of hospitalization was Euros 594,230.8, with a mean cost/episode: Euros
5,713.6 (SD 5,039.5). Mean cost/episode for adherence <= 75% was higher than >
75%, Euros 6,275.8 (SD 5,526.2) vs Euros 3,895.6 (SD 2,371.3), (p < 0.05, t
Student). CONCLUSIONS: The profile of this patient is fundamentally, a male
psychiatric or chronic cardiac patient with a degree of adherence <= 75% due to
abandoning domiciliary treatment. Admissions due to medication non-adherence are
associated with an important depletion of economic resources in the hospital.
PMID- 25137167
TI - [Toward a new model of pharmacy management comprehensive care of patients with
chronic kidney disease].
AB - OBJECTIVE: The treatment of chronic kidney disease represents 2.5% of the
National Healthcare System budget. Given the panorama of economic crisis, actions
aimed at containing the costs in this kind of pathologies should be implemented.
METHOD: Centralization of the management of the medications used for the
treatment of chronic kidney disease and its complications aims at reducing the
pharmaceutical expenditure. RESULTS: The new contracts of public healthcare
administrations with companies of dialysis centers establish a single price by
which the contractor takes care of the integral management of the patients,
including the dialysis therapy and pharmacological treatment. Drug management at
dialysis centers will be handled by specialized pharmacists by means of the
creation of pharmacy departments or drug warehouse. CONCLUSIONS: these measures
aim at improving healthcare of the patient in hemodialysis program, with health
benefits at a lower healthcare cost.
PMID- 25137165
TI - [Cost-effectiveness analysis of aflibercept in combination with FOLFIRI in the
treatment of patients with metastatic colorectal cancer].
AB - OBJECTIVES: To estimate the incremental cost per life-year gained (LYG) of
aflibercept in combination with FOLFIRI as second-line treatment in metastatic
colorectal cancer (mCRC) patients previously treated with oxaliplatin. METHODS:
Based on clinical trial VELOUR results, a three-state Markov model (stable
disease, progression and death) with 2-week cycle duration was designed.
Transition to health state "progression" implied the interruption of second-line
treatment and administration of a third-line treatment (post-second line
chemotherapy). Cost estimation included disease management cost (pharmaceutical,
adverse event management, administration costs, etc.). Both cost and outcomes
were discounted (3% annually). Sensitivity analyses (SA) were performed to test
model robustness. RESULTS: Administration of aflibercept + FOLFIRI as second-line
treatment provided 1.78 LYG (21 life-months gained). With FOLFIRI 1.43 LYG (17
months) were obtained. The cost of the clinical management of aflibercept +
FOLFIRI implied an additional investment of Euros 13,564 compared with FOLFIRI
for a lifetime horizon, being total costs for aflibercept + FOLFIRI of Euros
38,346, compared to Euros 24,782 with FOLFIRI. In the cost-effectiveness analysis
Euros 38,931/LYG was obtained with aflibercept in combination with FOLFIRI versus
FOLFIRI. CONCLUSION: Aflibercept in combination with FOLFIRI increased overall
survival versus FOLFIRI, so it is an effective strategy in the treatment of
patients with mCRC. Aflibercept in combination with FOLFIRI is an efficient
strategy for second-line mCRC treatment from the National Health System
perspective.
PMID- 25137168
TI - [Review of pharmacological interactions of oral anticancer drugs provided at
pharmacy department].
AB - OBJECTIVE: To identify the pharmacologic interactions of oral anti-cancer drugs
provided at an outpatient clinic. MATERIAL AND METHODS: Anti-cancer drugs
included in the Phamacotherapeutic Guideline of the Hospital were identified. A
literature search was carried out on the pharmacologic interactions in MEDLINE(r)
and EMBASE(r) (with the filer language English or Spanish, and the descriptors:
"name of the anti-cancer drug" AND ("drug interactions" OR "pharmacokinetic")),
Up-to-date(r), MICROMEDEX(r) and the drug information sheet for the EMA and the
FDA. Information was also gathered from the abstract presented to European and
Spanish scientific meetings for the last 4 years. When an interaction was
analyzed and had clinical relevance, the best pharmacotherapeutic interaction
free alternative was sought. RESULTS: Twenty-three drugs were identified, of
which Chlorambucil, Fludarabine, Lenalidomide, Melphalan, and Thalidomide were
the active compounds with the lowest likelihood of producing a pharmacologic
interaction. Tyrosine kinase inhibitors (particularly Erlotinib, Imatinib,
Lapatinib, and Pazopanib) are the drugs with highest number of pharmacologic
interactions described, many of them with severe clinical consequences, with
increases and decreases of the plasma levels of anti-cancer drugs. The active
compounds identified that may have pharmacologic interactions with anticancer
drugs were mainly: Allopurinol, Amiodarone, Carbamazepine, Dabigatran, Digoxin,
Spironolactone, Phenytoin, Itraconazol, Repaglinide, Silodosin, Tamoxifen,
Verapamil, and Warfarin. Pharmacologic interactions through the cytochrome P450
1A2, 2D6, 2C8, 2C9, 3A4 were the most important for tyrosine kinase inhibitors.
Other non-pharmacologic compounds, with an important potential of producing
relevant pharmacologic interaction were immunomodulators (Echinacea extracts) and
Hypericum perforatum. CONCLUSIONS: Oral anticancer drugs have numerous
pharmacologic interactions that should be monitored during pharmacotherapy. Given
its position, the hospital pharmacist is the key professional for identifying and
assessing the pharmacologic interactions or oral anticancer drugs that may have
clinical consequences.
PMID- 25137169
TI - [An update in drug use during pregnancy: risk classification].
AB - OBJECTIVE: To review medicines pregnancy category and establish the degree of
conformity between the two systems more used: FDA (Food and Drug Administration)
and ACPM (advisory Committee on Prescription Medicines). METHODS: drugs used in
most frequent pathologies during pregnancy have been selected and found its
pregnancy category according to FDA and ACPM. The degree of conformity has been
established between both categorisation systems. RESULTS: a total of 270
medicines were reviewed. 260 drugs had pregnancy category by FDA and 245 by ACPM
system. 232 drugs had pregnancy category defined by both classifications (FDA and
ACPM). We found 70,2% of them in the same pregnancy category. CONCLUSIONS: The
discrepancies found in both pregnancy categorisation systems can be confused in
order to prescribe and know its safety statement of medicines during pregnancy
which can limits its utility. It would be desirable more studies after medicines
registered to get more information which could help to use safety drugs during
pregnancy and minimize discrepancies between both pregnancy categorisation
systems.
PMID- 25137170
TI - [Treatment with urea as an alternative to tolvaptan for the syndrome of
inappropriate secretion of antidiuretic hormone].
PMID- 25137171
TI - [Are scientific literature databases a good source of scientific evidence for
discontinuing a drug from the market?].
PMID- 25137172
TI - [Systemic absorption of oral vancomycin in colitis patients. A propos of 2
cases].
PMID- 25137173
TI - [Management of systemic idiopathic juvenile arthritis in pediatrics with
biological agents: a propos of a case].
PMID- 25137174
TI - [Intralesional rituximab in ocular adnexal lymphoma].
PMID- 25137175
TI - Climatic niche conservatism and biogeographical non-equilibrium in Eschscholzia
californica (Papaveraceae), an invasive plant in the Chilean Mediterranean
region.
AB - Species climate requirements are useful for predicting their geographic
distribution. It is often assumed that the niche requirements for invasive plants
are conserved during invasion, especially when the invaded regions share similar
climate conditions. California and central Chile have a remarkable degree of
convergence in their vegetation structure, and a similar Mediterranean climate.
Such similarities make these geographic areas an interesting natural experiment
for testing climatic niche dynamics and the equilibrium of invasive species in a
new environment. We tested to see if the climatic niche of Eschscholzia
californica is conserved in the invaded range (central Chile), and we assessed
whether the invasion process has reached a biogeographical equilibrium, i.e.,
occupy all the suitable geographic locations that have suitable conditions under
native niche requirements. We compared the climatic niche in the native and
invaded ranges as well as the projected potential geographic distribution in the
invaded range. In order to compare climatic niches, we conducted a Principal
Component Analysis (PCA) and Species Distribution Models (SDMs), to estimate E.
californica's potential geographic distribution. We also used SDMs to predict
altitudinal distribution limits in central Chile. Our results indicated that the
climatic niche occupied by E. californica in the invaded range is firmly
conserved, occupying a subset of the native climatic niche but leaving a
substantial fraction of it unfilled. Comparisons of projected SDMs for central
Chile indicate a similarity, yet the projection from native range predicted a
larger geographic distribution in central Chile compared to the prediction of the
model constructed for central Chile. The projected niche occupancy profile from
California predicted a higher mean elevation than that projected from central
Chile. We concluded that the invasion process of E. californica in central Chile
is consistent with climatic niche conservatism but there is potential for further
expansion in Chile.
PMID- 25137176
TI - An efficient and highly versatile synthetic route to prepare iron oxide
nanoparticles/nanocomposites with tunable morphologies.
AB - We report a versatile synthetic method for the in situ self-assembly of magnetic
nanoparticle-functionalized polymeric nanomorphologies, including spherical
micelles and rod-like and worm-like micelles and vesicles. Poly(oligoethylene
glycol methacrylate)-block-(methacrylic acid)-block-poly(styrene) (POEGMA-b-PMAA
b-PST) triblock copolymer chains were simultaneously propagated and self
assembled via a polymerization-induced self-assembly (PISA) approach.
Subsequently, the carboxylic acid groups in the copolymers were used to complex
an iron ion (Fe(II)/Fe(III)) mixture. Iron oxide nanoparticles were then formed
in the central block, within the polymeric nanoparticles, via alkaline
coprecipitation of the iron(II) and (III) salts. Nanoparticle morphologies,
particle sizes, molecular weights, and chemical structures were then
characterized by transmission electron microscopy (TEM), dynamic light scattering
(DLS), size exclusion chromatography (SEC), and (1)H NMR measurements. TEM
micrographs showed that the average size of the magnetic nanoparticles was ~7 nm
at the hydrophobic/hydrophilic nexus contained within the nanoparticles. In
addition, XRD was used to confirm the formation of iron oxide nanoparticles.
Importantly, the polymeric nanoparticle morphologies were not affected by the
coprecipitation of the magnetic nanoparticles. The hybrid nanoparticles were then
evaluated as negative MRI contrast agents, displaying remarkably high transverse
relaxivities (r2, greater than 550 mM(-1) s(-1) at 9.4 T); a result, that we
hypothesize, ensues from iron oxide nanoparticle clustering at the hydrophobic
hydrophilic interface. This simple synthetic procedure is highly versatile and
produces nanocarriers of tunable size and shape with high efficacy as MRI
contrast agents and potential utility as theranostic delivery vectors.
PMID- 25137177
TI - A novel HoxB cluster protein expressed in the hindbrain and pharyngeal arches.
AB - We describe a novel zebrafish line that fluorescently tags a previously unknown
protein, CT74a, allowing us to follow its endogenous expression in real time and
at subcellular resolution in live embryos. Our results showed that CT74a-Citrine
fusion protein is expressed in the developing pharyngeal arches, hindbrain, and
fin buds in a pattern highly reminiscent of transcription factors belonging to
anterior Hox gene families, including expression in a subset of neuronal nuclei.
Consistent with this, splinkerette-PCR revealed that CT74a-Citrine's genomic
integration is within the HoxB region, and 3' RACE demonstrated that its
downstream coding sequence has no recognizable homology. Thus, CT74a is a
previously unknown protein located within the HoxB cluster adjacent to Hoxb4a and
is expressed in a Hoxb4a-like pattern.
PMID- 25137178
TI - LM and TEM study of the orthokeratinized and parakeratinized epithelium of the
tongue in the domestic duck (Anas platyrhynchos f. domestica).
AB - The previous histological studies of the lingual mucosa in birds characterized
two types of keratinized epithelium, i.e. orthokeratinized and parakeratinized.
These epithelia are composed of three layers: basal, intermediate and
keratinized. The present study showed detailed ultrastructural features of cells
in particular layers of two types of keratinized epithelia on the tongue in the
domestic duck and defined structural differences. TEM observations showed a
gradual reduction in cell organelles in the following layers, at increasing
amounts of keratin fibers. The characteristic feature of the ortho- and
parakeratinized epithelium is the presence of sub-layers in the intermediate
layer, i.e. the upper and lower part, which results from the different shape of
cell nuclei and dye affinity of the cytoplasm. The keratinized layer of ortho-
and parakeratinized epithelium is built of two types of cells such as electron
dark and light cells, which undergo exfoliation. The basic difference between the
keratinized epithelia is the presence of flattened cell nuclei in the keratinized
layer of the parakeratinized epithelium. The differentiating feature is also an
arrangement of keratin fibers in the cell cytoplasm of the keratinized layer. The
analysis of the thickness of the epithelium and the keratinized layer, indicated
differences between keratinized epithelia, which result from two variants of
performing protective functions, either through a thick keratinized layer or by a
higher epithelium. Differences in the ultrastructure of the ortho- and
parakeratinized epithelium are associated with mechanical functions of the
epithelium resulting from different forces acting on the tongue during feeding
activities.
PMID- 25137179
TI - Targeted theranostic prodrugs based on an aggregation-induced emission (AIE)
luminogen for real-time dual-drug tracking.
AB - A targeted theranostic delivery system containing two prodrugs with drug tracking
and activation monitoring functions was developed for visualizing cancer cell
ablation with synergistic anticancer effects.
PMID- 25137180
TI - The influence of Chinese one-child family status on developmental coordination
disorder status.
AB - We conducted a population-based study on Developmental Coordination Disorder
(DCD) in mainland China to explore the influence of one-child status in Chinese
families on DCD. A total of 4001 children selected from 160 classes in 15 public
nursery schools. The Movement Assessment Battery for Children assessed motor
function. The prevalence of DCD in Chinese one-child families (8.7%) was higher
than that in multi-child families (5.9%). Chinese one-child family status
(compared with younger children in multi-child families) were negatively related
with total score (-1.793), Manual dexterity (-0.228), Aiming and catching (
1.145), Balance (-0.433) of MABC-2 and DCD (OR=2.294) when adjusted for the
children's and family's characteristics, and perinatal factors (each p<0.05). As
one of the studies in this Chinese context, it provides a platform for future
intervention programs in one-child families in preventing children's
developmental disorders.
PMID- 25137182
TI - Yoga: a biobehavioral approach to reduce symptom distress in women with urge
urinary incontinence.
AB - Urge urinary incontinence is a debilitating chronic condition that poses
challenges for affected women and the clinicians who care for them.
Multicomponent behavioral therapies have shown promise in allowing women to
manage their symptoms. New evidence suggests an underlying pathophysiologic
inflammatory process for urge urinary incontinence, and complementary therapies
that address the psychoneuroimmunology component may improve the health and
quality of life for the millions of women with this condition. Yoga, a mind-body
therapy, has been shown to reduce inflammation and may help improve symptoms of
urge urinary incontinence. More research is necessary to demonstrate the
effectiveness of yoga to reduce urge urinary incontinence symptom burden and
improve quality of life.
PMID- 25137181
TI - Assessment of EGFR mutations in circulating tumor cell preparations from NSCLC
patients by next generation sequencing: toward a real-time liquid biopsy for
treatment.
AB - INTRODUCTION: Assessment of EGFR mutation in non-small cell lung cancer (NSCLC)
patients is mandatory for optimization of pharmacologic treatment. In this
respect, mutation analysis of circulating tumor cells (CTCs) may be desirable
since they may provide real-time information on patient's disease status.
EXPERIMENTAL DESIGN: Blood samples were collected from 37 patients enrolled in
the TRIGGER study, a prospective phase II multi-center trial of erlotinib
treatment in advanced NSCLC patients with activating EGFR mutations in tumor
tissue. 10 CTC preparations from breast cancer patients without EGFR mutations in
their primary tumors and 12 blood samples from healthy subjects were analyzed as
negative controls. CTC preparations, obtained by the Veridex CellSearch System,
were subjected to ultra-deep next generation sequencing (NGS) on the Roche 454 GS
junior platform. RESULTS: CTCs fulfilling all Veridex criteria were present in
41% of the patients examined, ranging in number between 1 and 29. In addition to
validated CTCs, potential neoplastic elements were seen in 33 cases. These
included cells not fulfilling all Veridex criteria (also known as "suspicious
objects") found in 5 (13%) of 37 cases, and isolated or clustered large naked
nuclei with irregular shape observed in 33 (89%) cases. EGFR mutations were
identified by NGS in CTC preparations of 31 (84%) patients, corresponding to
those present in matching tumor tissue. Twenty-five (96%) of 26 deletions at exon
19 and 6 (55%) of 11 mutations at exon 21 were detectable (P = 0.005). In 4 (13%)
cases, multiple EGFR mutations, suggesting CTC heterogeneity, were documented. No
mutations were found in control samples. CONCLUSIONS: We report for the first
time that the CellSearch System coupled with NGS is a very sensitive and specific
diagnostic tool for EGFR mutation analysis in CTC preparations with potential
clinical impact.
PMID- 25137183
TI - Physical exercise restores microvascular function in obese rats with metabolic
syndrome.
AB - BACKGROUND: Obesity and metabolic syndrome are related to systemic functional
microvascular alterations, including a significant reduction in microvessel
density. The aim of this study was to investigate the effects of exercise
training on functional capillary density in the skeletal muscle and skin of obese
rats with metabolic syndrome. METHODS: We used male Wistar-Kyoto rats that had
been fed a standard commercial diet (CON) or high-fat diet (HFD) for 32 weeks.
Animals receiving the HFD were randomly divided into sedentary (HFD+SED) and
training groups (HFD+TR) at the 20(th) week. After 12 weeks of aerobic treadmill
training, the maximal oxygen uptake (VO2max); hemodynamic, biochemical, and
anthropometric parameters; and functional capillary density were assessed. In
addition, a maximal exercise test was performed. RESULTS: Exercise training
increased the VO2max (69 +/- 3 mL/kg per min) and exercise tolerance (30 +/- 1
min) compared with the HFD+SED (41 +/- 6 mL/kg per min, P < 0.05 and 16 +/- 1
min, P < 0.001) and with the CON (52 +/- 7 mL/kg per min and 18 +/- 1 min, P <
0.05) groups. The HFD+TR group also showed reduced retroperitoneal fat (0.03 +/-
0.00 vs. 0.05 +/- 0.00 gram/gram, P < 0.001), epididymal fat (0.01 +/- 0.00 vs.
0.02 +/- 0.00 gram/gram, P < 0.001), and systolic blood pressure (127 +/- 2 vs.
150 +/- 2 mmHg, P<0.001). The HFD+TR group also demonstrated improved glucose
tolerance, as evaluated by an intraperitoneal glucose tolerance test, fasting
plasma glucose levels (5.0 +/- 0.1 vs. 6.4 +/- 0.2 mmol/L, P<0.001) and fasting
plasma insulin levels (26.5 +/- 2.3 vs. 38.9 +/- 3.7 MUIU/mL, P < 0.05). Glucose
tolerance did not differ between HFD+TR and CON groups. Exercise training also
increased the number of spontaneously perfused capillaries in the skeletal muscle
(252 +/- 9 vs. 207 +/- 9 capillaries/mm(2)) of the training group compared with
that in the sedentary animals (260 +/- 15 capillaries/mm(2)). CONCLUSIONS: These
results demonstrate that exercise training reverses capillary rarefaction in our
experimental model of metabolic syndrome and obesity.
PMID- 25137185
TI - Delay in seeking medical help following Transient Ischemic Attack (TIA) or "mini
stroke": a qualitative study.
AB - BACKGROUND: Prompt treatment following Transient Ischemic Attack (TIA) can reduce
the risk of subsequent stroke and disability. However, many patients delay in
making contact with medical services. This study aimed to explore TIA patients'
accounts of delay between symptom onset and contacting medical services including
how decisions to contact services were made and the factors discussed in relation
to delay. METHODS: Twenty interviews were conducted with TIA patients in England.
Using a previous systematic review as an initial framework, interview data were
organised into categories of symptom recognition, presence of others and type of
care sought. A thematic analysis was then conducted to explore descriptions of
care-seeking relevant to each category. RESULTS: Delay in contacting medical
services varied from less than an hour to eight days. Awareness of typical stroke
symptoms could lead to urgent action when more severe TIA symptoms were present
but could lead to delay when experienced symptoms were less severe. The role of
friends and family varied widely from deciding on and enacting care-seeking
decisions to simply providing transport to the GP practice. When family or
friends played a greater role, and both made and enacted care-seeking decisions,
delays were often shorter, even when patients themselves failed to identify
symptoms. Healthcare professionals also impacted on patients' care-seeking with
greater delays in seeking further care for the same episode described when
patients perceived a lack of urgency during initial healthcare interactions.
CONCLUSIONS: This study provides new information on patients' decisions to
contact medical services following TIA and identifies overlapping factors that
can lead to delay in receiving appropriate treatment. While recognition of
symptoms may contribute to delay in contacting medical services, additional
factors, including full responsibility being taken by others and initial
healthcare interactions, can over-ride or undermine the importance of patients'
own identification of TIA.
PMID- 25137187
TI - From the Editor-in-Chief's Desk.
PMID- 25137186
TI - CTAG-containing cleavage site profiling to delineate Salmonella into natural
clusters.
AB - BACKGROUND: The bacterial genus Salmonella contains thousands of serotypes that
infect humans or other hosts, causing mild gastroenteritis to potentially fatal
systemic infections in humans. Pathogenically distinct Salmonella serotypes have
been classified as individual species or as serological variants of merely one or
two species, causing considerable confusion in both research and clinical
settings. This situation reflects a long unanswered question regarding whether
the Salmonella serotypes exist as discrete genetic clusters (natural species) of
organisms or as phenotypic (e.g. pathogenic) variants of a single (or two)
natural species with a continuous spectrum of genetic divergence among them. Our
recent work, based on genomic sequence divergence analysis, has demonstrated that
genetic boundaries exist among Salmonella serotypes, circumscribing them into
clear-cut genetic clusters of bacteria. METHODOLOGIES/PRINCIPAL FINDINGS: To
further test the genetic boundary concept for delineating Salmonella into clearly
defined natural lineages (e.g., species), we sampled a small subset of conserved
genomic DNA sequences, i.e., the endonuclease cleavage sites that contain the
highly conserved CTAG sequence such as TCTAGA for XbaI. We found that the CTAG
containing cleavage sequence profiles could be used to resolve the genetic
boundaries as reliably and efficiently as whole genome sequence comparisons but
with enormously reduced requirements for time and resources. CONCLUSIONS:
Profiling of CTAG sequence subsets reflects genetic boundaries among Salmonella
lineages and can delineate these bacteria into discrete natural clusters.
PMID- 25137189
TI - Lurasidone treatment in a child with autism spectrum disorder with irritability
and aggression.
PMID- 25137188
TI - Childhood depression subscales using repeated sessions on Children's Depression
Rating Scale - revised (CDRS-R) scores.
AB - BACKGROUND: Although acute treatments have been shown to be effective in treating
early-onset depression, only one-third or thereabouts reach a remission within 3
months. Unfortunately, delayed time to remission in early-onset depression leads
to poorer therapeutic outcomes. Clearly, there is a need to identify, diagnose,
and provide effective treatment of a depressed patient quickly. A sophisticated
understanding of depression subscales and their change over time with treatment
could enhance pathways to individualized treatment approaches for childhood
depression. OBJECTIVE: Previous studies have found that the clinician-measured
instrument, Children's Depression Rating Scale-Revised (CDRS-R) measures multiple
subscales (or components) of depression. The aim of this study was to see how
these subscales may change over the course of a 12-week study. This knowledge
will help determine if dimensions/subscales of childhood depression (paralleling
the adult literature) using the subscales derived from factor analysis procedure
is useful. METHODS: We examined two clinical trials in which youth (n=234) with
major depressive disorder (MDD) were treated openly with fluoxetine for eight
sessions spread over 12 weeks. The CDRS-R was completed based on clinician
interviews with parent and child at each session. Classical test theory and
component analysis with associated parallel analysis (oblique rotation) were
conducted on each week's scores. RESULTS: Although more factors were needed for
the baseline and first two therapy sessions, a two-factor solution sufficed
thereafter. Depressed facial affect, listless speech, and hypoactivity best
defined Factor I, whereas sleep problems, appetite disturbance, physical
symptoms, irritability, guilt, and weeping best defined Factor II. All other
symptoms cross-loaded almost equally on the two factors. The scale's reliability
(internal consistency) improved from baseline to exit sessions (alpha=0.65-0.91).
As a result, the clinicians' assessments of the various symptoms became more
highly related to one another. This caused the first eigenvalue to increase from
3.24 to 7.38 and the variance explained to increase (%) from 19% to 43% over
sessions. These two factors may reflect 1) clinician-observed signs and 2)
reported symptoms of depression. CONCLUSIONS: Factor analysis of CDRS-R data in a
single session consistently generates a complex and difficult to interpret
structure of at least three factors. This makes it very difficult to understand
what these factors measure. However, when gathered over additional sessions, the
CDRS-R structure tends to simplify to two factors. The reasons for this
simplification are as yet unclear and in need of further study.
PMID- 25137192
TI - Monitoring cellular stress responses using integrated high-frequency impedance
spectroscopy and time-resolved ELISA.
AB - We have developed a lab-on-a-chip system for continuous and non-invasive
monitoring of microfluidic cell cultures using integrated high-frequency
contactless impedance spectroscopy. Electrically insulated microfabricated
interdigitated electrode structures were embedded into four individually
addressable microchambers to reliably and reproducibly detect cell-substrate
interactions, cell viability and metabolic activity. While silicon nitride
passivated sensor substrates provided a homogeneous cell culture surface that
minimized cell orientation along interdigitated electrode structures, the
application of high-frequency AC fields reduced the impact of the 300 nm thick
passivation layer on sensor sensitivity. The additional implementation of
multivariate data analysis methods such as partial least square (PLS) for high
frequency impedance spectra provided unambiguous information on intracellular
pathway activation, up and down-regulation of protein synthesis as well as global
cellular stress responses. A comparative cell analysis using connective tissue
fibroblasts showed that high-frequency contactless impedance spectroscopy and
time-resolved quantification of IL-6 secretion using ELISA provided similar
results following stimulation with circulating pro-inflammatory cytokines IL
1beta and TNFalpha. The combination of microfluidics with contactless impedance
sensing and time-resolved quantification of stress factor release will provide
biologist with a new tool to (a) establish a variety of uniform cell culture
surfaces that feature complex biochemistries, micro- and nanopatterns; and (b) to
simultaneously characterize cell responses under physiologically relevant
conditions using a complementary non-invasive cell analysis method.
PMID- 25137193
TI - Sequence specific detection of restriction enzymes at DNA-modified carbon
nanotube field effect transistors.
AB - Protein-DNA interactions play a central role in many cellular processes, and
their misregulation has been implicated in a number of human diseases. Thus,
there is a pressing need for the development of analytical strategies for
interrogating the binding of proteins to DNA. Herein, we report the electrical
monitoring of a prototypical DNA-binding protein, the PvuII restriction enzyme,
at microfluidic-encapsulated, DNA-modified carbon nanotube field effect
transistors. Our integrated platform enables the sensitive, sequence specific
detection of PvuII at concentrations as low as 0.5 pM in a volume of 0.025 MUL
(corresponding to ~7500 proteins). These figures of merit compare favorably to
state of the art values reported for alternative fluorescent and electrical
assays. The overall detection strategy represents a step toward the massively
parallel electrical monitoring, identification, and quantification of protein-DNA
interactions at arrayed nanoscale devices.
PMID- 25137194
TI - Plasmonic effects of au/ag bimetallic multispiked nanoparticles for photovoltaic
applications.
AB - In recent years, there has been considerable interest in the use of plasmons,
that is, free electron oscillations in conductors, to boost the performance of
both organic and inorganic thin film solar cells. This has been driven by the
possibility of employing thin active layers in solar cells in order to reduce
materials costs, and is enabled by significant advances in fabrication
technology. The ability of surface plasmons in metallic nanostructures to guide
and confine light in the nanometer scale has opened up new design possibilities
for solar cell devices. Here, we report the synthesis and characterization of
highly monodisperse, reasonably stable, multipode Au/Ag bimetallic nanostructures
using an inorganic additive as a ligand for photovoltaic applications. A
promising surface enhanced Raman scattering (SERS) effect has been observed for
the synthesized bimetallic Au/Ag multispiked nanoparticles, which compare
favorably well with their Au and Ag spherical nanoparticle counterparts. The
synthesized plasmonic nanostructures were incorporated on the rear surface of an
ultrathin planar c-silicon/organic polymer hybrid solar cell, and the overall
effect on photovoltaic performance was investigated. A promising enhancement in
solar cell performance parameters, including both the open circuit voltage (VOC)
and short circuit current density (JSC), has been observed by employing the
aforementioned bimetallic multispiked nanoparticles on the rear surface of solar
cell devices. A power conversion efficiency (PCE) value as high as 7.70% has been
measured in a hybrid device with Au/Ag multispiked nanoparticles on the rear
surface of an ultrathin, crystalline silicon (c-Si) membrane (~ 12 MUm). This
value compares well to the measured PCE value of 6.72% for a similar device
without nanoparticles. The experimental observations support the hope for a
sizable PCE increase, due to plasmon effects, in thin-film, c-Si solar cells in
the near future.
PMID- 25137195
TI - Feasibility of ballistic strengthening exercises in neurologic rehabilitation.
AB - Conventional methods for strength training in neurologic rehabilitation are not
task specific for walking. Ballistic strength training was developed to improve
the functional transfer of strength training; however, no research has
investigated this in neurologic populations. The aim of this pilot study was to
evaluate the feasibility of applying ballistic principles to conventional leg
strengthening exercises in individuals with mobility limitations as a result of
neurologic injuries. Eleven individuals with neurologic injuries completed seated
and reclined leg press using conventional and ballistic techniques. A 2 * 2
repeated-measures analysis of variance was used to compare power measures (peak
movement height and peak velocity) between exercises and conditions. Peak jump
velocity and peak jump height were greater when using the ballistic jump
technique rather than the conventional concentric technique (P < 0.01). These
findings suggest that when compared with conventional strengthening exercises,
the incorporation of ballistic principles was associated with increased peak
height and peak velocities.
PMID- 25137197
TI - The World Health Organization disability action plan.
PMID- 25137196
TI - Contralateral lumbar radicular pain shortly after a transforaminal epidural
steroid injection: an unusual sequel.
PMID- 25137198
TI - [Anesthesiologists teach teachers, teachers train students, students are
lifesavers!].
PMID- 25137200
TI - [Case report: Aneurysmatic subarachnoid hemorrhage -- complicated course due to
coincidental manifestation of an inverted Tako-Tsubo-cardiomyopathy].
AB - We report the case of a patient who suffered a serious subarachnoid hemorrhage
with a cardialaffection and development of an inverted Tako-Tsubo-cardiomyopathy.
To avoid apparent cerebral ischemia due to severe cerebral vasospasm after
exhaustion of conservative therapeutic options a temporarily endovascular therapy
with continuous intra-arterial application of Nimodipine was necessary. In the
overall protracted and complicated course the special challenge were the
therapeutic efforts to avoid apparent cerebral ischemia in context to the
significant cardial affection.
PMID- 25137201
TI - [Subsyndromal delirium -- experience in psychiatry -- expectations for
postoperative management].
AB - The phenomenon of delirium is well known since over 100 years. The anesthesiology
has recognized that early detection and therapy results in significant
improvement of postoperative clinical state of health of the patients. In the
following article it will be discussed that it could be profitable to make a
further step: threatening the subsyndromal delirium. Because there are only few
experiences in anesthesiology, this thesis will be substantiated by datas from
psychiatry.
PMID- 25137202
TI - [Resuscitation between the guidelines -- what has happened since 2010].
AB - The standards of treatment of patients suffering cardiac arrest is defined by
international guidelines for cardiopulmonary resuscitation, that are updated
every five years. Scientific knowledge is continuously increasing and recent
studies should be considered and discussed to improve the results of daily
emergency care. There are some leading topics of the ongoing discussion
concerning airwaymanagement, mechanical ventilation, mechanical cpr-devices and
extracorporal life support. The strategies of postresuscitation care are also in
the focus of interest. This review presents and discusses the value of recent
investigations on resuscitation science.
PMID- 25137203
TI - [Patient safety -- mission for the future: Anesthesia -- but sure!].
PMID- 25137204
TI - [Patient safety -- mission for the future: Managing complications: what do I tell
to the patients and what to the relatives?].
AB - In cases of unintended treatment courses an adequate communication is mandatory.
Empathetic conversations expressing human warmth can pave the way to the
avoidance of forensic consequences. The laws on patient's rights obligate the
responsible physician to inform on request the patient about all recognizable
circumstances that may lead to the assumption of a treatment error and to avoid
hazards to health. The patient has a right to view his or her complete patient
records and to demand that copy be made at the patient's expense. In the case of
information to relatives the physician must observe the content and scope of
his/her obligation to medical confidentiality.
PMID- 25137205
TI - [Patient safety -- mission for the future: Recommendations for the management of
severe treatment complications and burdensome courses (preventing the "second
victim")].
AB - Avoiding complications is a major goal of all patient safety efforts. We are used
to working with all kinds of algorithms for avoiding adverse events or for the
diagnosis and treatment of possible unforeseen or inadvertent complications in
our patients. As a matter of fact, severe complications certainly have an impact
not only on the patient, but also on the medical team involved ("second victim").
Obviously there is no published standard in Germany on how to deal with this
professional problem. Therefore, the German Society of Anaesthesiology and
Intensive Care Medicine (DGAI) has elaborated guidelines for the individual
professional concerned, for the colleagues of doctors involved, as well as for
the supervisors and hospital institutions. The aim of these recommendations is to
encourage our professional society to set a focus on this problem and to offer a
structured course of action for the case that a major complication occurs in
spite of all our efforts to maintain our patient's safety.
PMID- 25137206
TI - [Patient safety -- mission for the future: The importance of Critical Incident
Reporting Systems (CIRS) in clinical practice].
AB - Every day patients experience harm due to errors and complications. To improve
this situation, patient safety is increasingly becoming important in the
treatment process. One aspect to increase patient safety is the Critical Incident
Reporting System (CIRS). Observers and members of the care team are given the
opportunity to anonymously report critical incidents and thus allow an analysis
by an evaluation team. The goal is not to sanction the behavior of an individual,
but to identify particular structural and organizational sources of error and to
derive improvements.
PMID- 25137207
TI - [Patient safety -- mission for the future: Healthcare-associated infections and
antibiotic resistance].
AB - Healthcare-associated infections (HAI) are considered as one of the major
challenges for modern health care. In the context of demographic change and the
expected increase of invasive and complex patient treatment and concommittantrise
in numbers of patients with underlying diseases with susceptibility to
infections, quality of care and patient safety will in the near future depend
strongly on the prevention of HAI. To avoid preventable HAI in terms of improved
quality of care is beyond question, therefore mainly the prevalence of highly
resistant microorganisms (HRMO) will becrucial for the success of treatment of
unpreventable HAI. In addition to MRSA, the greatest danger in relation to
antibiotic resistance worldwide are now considered tob e carbapenem-resistant
Enterobacteriaceae (CRE) or multidrug-resistant Gram-negative (4MRGN) bacteria.
In case oft he uncontrolled spread of HRMO unpreventable infections become also
untreatable. The prevalence of HRMO varies between different countries.
Especially in the Netherlands and Denmark HRMO such as MRSA, VRE and CRE/4MRGN
are still significantly less common than in Germany or France. The reason lies in
the fact that in nearly all Dutch hospitals anintegrative infectious disease
service (clinical microbiology and/or infectious diseaseas wellinfection
prevention) was established already years ago, while in Germany - with few
exceptions - in most hospitals only a basic infectious disease services
(consulting hygienist, microbiological diagnosis is held by laboratories often
far away from the patient). As hospitals are connected with each other with
respect to theircommon care of patients, one of the most important challenges in
future infection prevention will be the implementation of regional and
intersectoral infection prevention and control.
PMID- 25137208
TI - [Scientific Update: ARDS and ECMO -- 4th ARDS/ECMO Symposium in Marburg].
PMID- 25137211
TI - Cardiac Transplants With Cyclosporin-A and Low-Dose Prednisone: Histologic
Graduation of Rejection.
PMID- 25137212
TI - Hydraphile synthetic ion channels alter root architecture in Arabidopsis
thaliana.
AB - The presence of low concentrations of hydraphile synthetic amphiphiles have been
found to dramatically alter the primary/lateral root architectural balance in the
A. thaliana plant model system and a correlation to ion transport by the
hydraphiles is consistent with the effects.
PMID- 25137213
TI - Dissolution, agglomerate morphology, and stability limits of protein-coated
silver nanoparticles.
AB - Little is understood regarding the impact that molecular coatings have on
nanoparticle dissolution kinetics and agglomerate formation in a dilute
nanoparticle dispersion. Dissolution and agglomeration processes compete in
removing isolated nanoparticles from the dispersion, making quantitative time
dependent measurements of the mechanisms of nanoparticle loss particularly
challenging. In this article, we present in situ ultra-small-angle X-ray
scattering (USAXS) results, simultaneously quantifying dissolution,
agglomeration, and stability limits of silver nanoparticles (AgNPs) coated with
bovine serum albumin (BSA) protein. When the BSA corona is disrupted, we find
that the loss of silver from the nanoparticle core is well matched by a second
order kinetic rate reaction, arising from the oxidative dissolution of silver.
Dissolution and agglomeration are quantified, and morphological transitions
throughout the process are qualified. By probing the BSA-AgNP suspension around
its stability limits, we provide insight into the destabilization mechanism by
which individual particles rapidly dissolve as a whole rather than undergo slow
dissolution from the aqueous interface inward, once the BSA layer is breached.
Because USAXS rapidly measures over the entire nanometer to micrometer size range
during the dissolution process, many insights are also gained into the
stabilization of NPs by protein and its ability to protect the labile metal core
from the solution environment by prohibiting the diffusion of reactive species.
This approach can be extended to a wide variety of coating molecules and reactive
metal nanoparticle systems to carefully survey their stability limits, revealing
the likely mechanisms of coating breakdown and ensuing reactions.
PMID- 25137214
TI - High-performance ionic diode membrane for salinity gradient power generation.
AB - Salinity difference between seawater and river water is a sustainable energy
resource that catches eyes of the public and the investors in the background of
energy crisis. To capture this energy, interdisciplinary efforts from chemistry,
materials science, environmental science, and nanotechnology have been made to
create efficient and economically viable energy conversion methods and materials.
Beyond conventional membrane-based processes, technological breakthroughs in
harvesting salinity gradient power from natural waters are expected to emerge
from the novel fluidic transport phenomena on the nanoscale. A major challenge
toward real-world applications is to extrapolate existing single-channel devices
to macroscopic materials. Here, we report a membrane-scale nanofluidic device
with asymmetric structure, chemical composition, and surface charge polarity,
termed ionic diode membrane (IDM), for harvesting electric power from salinity
gradient. The IDM comprises heterojunctions between mesoporous carbon (pore size
~7 nm, negatively charged) and macroporous alumina (pore size ~80 nm, positively
charged). The meso-/macroporous membrane rectifies the ionic current with
distinctly high ratio of ca. 450 and keeps on rectifying in high-concentration
electrolytes, even in saturated solution. The selective and rectified ion
transport furthermore sheds light on salinity-gradient power generation. By
mixing artificial seawater and river water through the IDM, substantially high
power density of up to 3.46 W/m(2) is discovered, which largely outperforms some
commercial ion-exchange membranes. A theoretical model based on coupled Poisson
and Nernst-Planck equations is established to quantitatively explain the
experimental observations and get insights into the underlying mechanism. The
macroscopic and asymmetric nanofluidic structure anticipates wide potentials for
sustainable power generation, water purification, and desalination.
PMID- 25137215
TI - Self-regulation and protective health behaviour: how regulatory focus and
anticipated regret are related to vaccination decisions.
AB - OBJECTIVE: We examined how individual motivational orientations and anticipated
regret are related to the protective health decision of vaccination behaviour.
DESIGN: The proposed relations were examined in a large-scale sample (N = 3168)
and three medium-sized samples (N = 151, N = 194, N = 208). Questionnaires were
applied to assess regulatory focus, anticipated regret and vaccination behaviour.
RESULTS: Increased prevention-focused self-regulation - which is represented by
concerns about security-related goals, responsibilities and obligations - was
related to a greater likelihood of vaccination. Prevention-focused individuals'
higher likelihood of getting vaccinated seems at least in part to be a
consequence of anticipated regret for not vaccinating. Study 3 suggests that
regulatory focus is less related to vaccination decisions when regret is
increased by the decision-making context; that is, when information highlighting
vaccination effectiveness and a low likelihood of adverse responses is provided.
CONCLUSION: Prevention-focused self-regulation is related to a greater likelihood
of engaging in health-protective behaviour. This can be explained by prevention
focused individuals' greater tendency to anticipate regret about getting ill as a
consequence of not adopting protective measures. If people perceive a protective
measure such as a vaccination as highly effective, anticipated regret for not
adopting it is generally increased, and individual differences in regulatory
focus no longer predict the decision.
PMID- 25137217
TI - Single-molecule-magnet behavior in the family of [Ln(OETAP)2] double-decker
complexes (Ln=lanthanide, OETAP=octa(ethyl)tetraazaporphyrin).
AB - Double-decker complexes of lanthanide cations can be readily prepared with
tetraazaporphyrins (porphyrazines). We have synthesized and characterized a
series of neutral double-decker complexes [Ln(OETAP)2 ] (Ln=Tb(3+), Dy(3+),
Gd(3+), Y(3+); OETAP=octa(ethyl)tetraazaporphyrin). Some of these complexes show
analogous magnetic features to their phthalocyanine (Pc) counterparts. The Tb(3+)
and Dy(3+) derivatives exhibit single-molecule magnet (SMM) behavior with high
blocking temperatures over 50 and 10 K, respectively. These results confirm that,
in double-decker complexes that involve Tb or Dy, the (N4)2 square antiprism
coordination mode has an important role in inducing very large activation
energies for magnetization reversal. In contrast with their Pc counterparts, the
use of tetraazaporphyrin ligands endows the presented [Ln(OETAP)2] complexes with
extraordinary chemical versatility. The double-decker complexes that exhibit SMM
behavior are highly soluble in common organic solvents, and easily processable
even through sublimation.
PMID- 25137216
TI - Replacing intrusive thoughts: investigating thought control in relation to OCD
symptoms.
AB - BACKGROUND AND OBJECTIVES: Control of obsessive thoughts in Obsessive Compulsive
Disorder (OCD) involves both avoidance and removal of undesirable intrusive
thoughts. Thought suppression tasks tap both of these processes but experimental
results have been inconsistent. Experimental tasks allowing more focused study of
the processes involved in controlling intrusive thoughts may be needed. In two
experiments, control over neutral, standardized intrusive and personal intrusive
thoughts was investigated as participants attempted to replace them with neutral
thoughts. METHODS: Non-selected university students (Experiment 1: N = 61) and
university students scoring high and low on self-report measure of OC symptoms
(Experiment 2: N = 40) performed a computerized thought replacement task.
RESULTS: In experiment 1 replacing personal intrusive thoughts took longer than
replacing neutral thoughts. Self-reports showed that intrusive thoughts were
rated more difficult to replace and were associated with greater thought
reoccurrence during replacement, larger emotional reaction and more discomfort.
These results were largely replicated in experiment 2. Furthermore, the high OC
symptom group experienced greater overall difficulty controlling thoughts on the
replacement task, experienced more reoccurrences of personal intrusive thoughts,
larger emotional reactions and discomfort associated with them, and felt a
greater urge to remove them. LIMITATIONS: All participants were non-clinical
university students, and older adults with OCD should be tested. CONCLUSIONS: The
findings are in line with cognitive behavioural theories of OCD. They support the
usefulness of thought replacement as a research paradigm to study thought control
in OCD and possibly other psychological conditions characterized by repetitive
thoughts.
PMID- 25137218
TI - Layered double hydroxide-based nanomaterials as highly efficient catalysts and
adsorbents.
AB - Layered double hydroxides (LDHs) are a class of anion clays consisting of brucite
like host layers and interlayer anions, which have attracted increasing interest
in the fields of catalysis/adsorption. By virtue of the versatility in
composition, morphology, and architecture of LDH materials, as well as their
unique structural properties (intercalation, topological transformation, and self
assembly with other functional materials), LDHs display great potential in the
design and fabrication of nanomaterials applied in photocatalysis, heterogeneous
catalysis, and adsorption/separation processes. Taking advantage of the
structural merits and various control synthesis strategies of LDHs, the active
center structure (e.g., crystal facets, defects, geometric and electronic states,
etc.) and macro-nano morphology can be facilely manipulated for specific
catalytic/adsorbent processes with largely enhanced performances. In this review,
the latest advancements in the design and preparation of LDH-based functional
nanomaterials for sustainable development in catalysis and adsorption are
summarized.
PMID- 25137219
TI - Evidence that neurovascular coupling underlying the BOLD effect increases with
age during childhood.
AB - Functional MRI using blood-oxygen-level-dependent (BOLD) imaging has provided
unprecedented insights into the maturation of the human brain. Task-based fMRI
studies have shown BOLD signal increases with age during development (ages 5-18)
for many cognitive domains such as language and executive function, while
functional connectivity (resting-state) fMRI studies investigating regionally
synchronous BOLD fluctuations have revealed a developing functional organization
of the brain from a local into a more distributed architecture. However,
interpretation of these results is confounded by the fact that the BOLD signal is
directly related to blood oxygenation driven by changes in blood flow and only
indirectly related to neuronal activity, and may thus be affected by changing
neuronal-vascular coupling. BOLD signal and cerebral blood flow (CBF) were
measured simultaneously in a cohort of 113 typically developing awake
participants ages 3-18 performing a narrative comprehension task. Using a novel
voxelwise wild bootstrap analysis technique, an increased ratio of BOLD signal to
relative CBF signal change with age (indicative of increased neuronal-vascular
coupling) was seen in the middle temporal gyri and the left inferior frontal
gyrus. Additionally, evidence of decreased relative oxygen metabolism (indicative
of decreased neuronal activity) with age was found in the same regions. These
findings raise concern that results of developmental BOLD studies cannot be
unambiguously attributed to neuronal activity. Astrocytes and astrocytic
processes may significantly affect the maturing functional architecture of the
brain, consistent with recent research demonstrating a key role for astrocytes in
mediating increased CBF following neuronal activity and for astrocyte processes
in modulating synaptic connectivity.
PMID- 25137220
TI - Semiparametric adjusted exposure-response curves.
AB - Exposure-response curves are central to understanding how continuous exposures
relate to health outcomes. Common methods to plot such curves include the use of
crude and adjusted regression, with the exposure specified using fractional
polynomials or regression splines. These approaches are subject to important
limitations. In this article, we illustrate the use of semiparametric marginally
adjusted exposure-response curves obtained via inverse probability weighting. We
explore the relation between interpregnancy interval and preterm birth in a
cohort of over 720,000 live births in Quebec between 1989 and 2008. We include
online supplementary material showing how mixed modeling routines in standard
software packages can be used to implement the procedure, and how pointwise
bootstrap confidence intervals can be obtained.
PMID- 25137221
TI - Effectiveness of three different walking prescription durations on total physical
activity in normal- and overweight women.
AB - OBJECTIVE: While there is a dose-response relationship between physical activity
(PA) and health benefit, little is known about the effectiveness of different PA
prescriptions on total daily PA. AIM: To test, under real-life conditions and
using an objective, non-invasive measurement technique (accelerometry), the
effect of prescribing additional physical activity (walking only) of different
durations (30, 60 and 90 min/day) on compliance (to the activity prescribed) and
compensation (to total daily PA). Participants in each group were prescribed 5
sessions of walking per week over 4 weeks. METHODS: 55 normal-weight and
overweight women (mean BMI 25 +/- 5 kg/m(2), height 165 +/- 1 cm, weight 68 +/- 2
kg and mean age 27 +/- 1 years) were randomly assigned to 3 prescription groups:
30, 60 or 90 min/day PA. RESULTS: Walking duration resulted in an almost linear
increase in the number of steps per day during the prescription period from an
average of about 10,000 steps per day for the 30-min prescription to about 14,000
for the 90-min prescription. Compliance was excellent for the 30-min prescription
but decreased significantly with 60-min and 90-min prescriptions. In parallel,
degree of compensation subsequent to exercise increased progressively as length
of prescription increased. CONCLUSION: A 30-min prescription of extra walking 5
times per week was well tolerated. However, in order to increase total PA
further, much more than 60 min of walking may need to be prescribed in the
majority of individuals. While total exercise 'volume' increased with
prescriptions longer than 30 min, compliance to the prescription decreased and
greater compensation was evident.
PMID- 25137222
TI - Squamous cell carcinoma of the skin (non-metastatic).
AB - INTRODUCTION: Cutaneous squamous cell carcinoma is a malignant tumour of
keratinocytes arising in the epidermis, with histological evidence of dermal
invasion. Incidence varies by country, skin colour, and outdoor behaviour, and is
as high as 400/100,000 in Australia. People with fair skin colour who have high
sun exposure and sunburn easily with little or no tanning, people with xeroderma
pigmentosum, and people who are immunosuppressed are most susceptible to squamous
cell carcinoma. METHODS AND OUTCOMES: We conducted a systematic review and aimed
to answer the following clinical questions: Does the use of sunscreen help
prevent cutaneous squamous cell carcinoma and actinic (solar) keratosis? What is
the optimal margin for primary excision of cutaneous squamous cell carcinoma (non
metastatic)? Does radiotherapy after surgery affect local recurrence of cutaneous
squamous cell carcinoma in people with squamous cell carcinoma of the skin (non
metastatic)? We searched: Medline, Embase, The Cochrane Library, and other
important databases up to August 2013 (Clinical Evidence reviews are updated
periodically, please check our website for the most up-to-date version of this
review). We included harms alerts from relevant organisations such as the US Food
and Drug Administration (FDA) and the UK Medicines and Healthcare products
Regulatory Agency (MHRA). RESULTS: We found five studies that met our inclusion
criteria. We performed a GRADE evaluation of the quality of evidence for
interventions. CONCLUSIONS: In this systematic review, we present information
relating to the effectiveness and safety of the following interventions:
sunscreens, primary excision, and radiotherapy after surgery.
PMID- 25137223
TI - Deposition of Particles in Human Mouth-Throat Replicas and a USP Induction Port.
AB - BACKGROUND: Oral inhalation is the common route of drug delivery to pulmonary
airways. In general, deposition in the oropharyngeal airways from a drug-delivery
device makes up a substantial portion of the emitted dose, which affects the dose
delivered to the lung. Studies with airway replicas made from cadaver or magnetic
resonance imaging scans show that for micrometer-sized particles, impaction is
the dominant deposition mechanism. Several deposition studies in oropharyngeal
replicas found that the deposition efficiency can be correlated with the mouth
inlet velocity and inlet mouthpiece diameter. Other studies show that the
deposition efficiency is best correlated with the mean diameter of internal
geometry and the mean velocity based on the mean diameter. METHOD: We
investigated the mouth inlet diameter, as well as internal airway dimensions and
their influence on oropharyngeal deposition based on experimental data from this
study. Several human oropharyngeal replicas with different mouth inlet diameters
and the USP induction port were used. RESULTS: We found that the aerosol
deposition increased with decreasing mouth inlet diameter. Several mathematical
expressions were tried to correlate the deposition efficiency with the Stokes
number calculated based on (1) mouth inlet diameter and inlet velocity, (2) mean
diameter of internal geometry and mean velocity, (3) mouth inlet velocity and
mean diameter, and (4) mouth inlet velocity and minimum diameter in the
oropharyngeal replica. The best correlation was obtained in case 4. CONCLUSIONS:
This correlation could explain the intra-subject variation when deposition was
found to vary with mouth inlet diameter, such as in some aerosol drug-delivery
devices. It could also explain the intersubject variability in oropharyngeal
deposition when human volunteers with different airway geometries and mouth
openings were studied.
PMID- 25137224
TI - Protective effects of escin against indomethacin-induced gastric ulcer in mice.
AB - Escin, a natural mixture of triterpenoid saponin isolated from the seed of the
horse chestnut, is reported to have a potent antiulcer activity against ethanol
induced gastric mucosal lesions. This study investigated the possible mechanisms
underlying the gastroprotective effect of escin against indomethacin-induced
gastric ulcer in mice. Gastric ulceration was induced by a single intragastric
administration of indomethacin (18 mg/kg). The mice underwent intragastric
treatment with escin at doses of 0.45, 0.9 or 1.8 mg/kg. Gastric lesion was
estimated morphometrically and histopathologically 6 h after the indomethacin
administration. The antioxidative parameters in gastric mucosa were measured.
Moreover, the activity of myeloperoxidase and the contents of TNF-alpha, P
selectin and VCAM-1 in gastric tissues were determined. The results showed that
escin protected gastric tissues against indomethacin-induced gastropathy as
demonstrated from a reduction in the ulcer index and an attenuation of
histopathologic changes. Escin caused significant reductions of the contents of
malondialdehyde, TNF-alpha, P-selectin, VCAM-1 and myeloperoxidase activity. The
altered activities of superoxide dismutase, catalase and glutathione peroxidase
in the stomach tissues were also ameliorated by escin treatment. The present
study demonstrated that escin had a protective effect against indomethacin
induced gastric ulcer in mice, not only by virtue of its antioxidant potential,
but also due to its anti-inflammatory effect.
PMID- 25137228
TI - Spectroscopic study of jet-cooled deuterated porphycenes: unusual isotopic
effects on proton tunneling.
AB - Porphycene (Pc) is a well-known model for studying double hydrogen transfer,
which shows vibrational-mode-specific tunneling splitting when isolated in
supersonic jets or helium nanodroplets. The effect of deuteration on tunneling
splitting is reported for jet-cooled heterogeneous, deuterated Pc samples (Pc
d(mix)) with the prevailing contribution of Pc-d12 isotopologue. The sample
introduced into the gas phase using laser desorption is studied by means of laser
induced fluorescence (LIF) and single vibronic level fluorescence (SVLF)
measurements, in combination with quantum chemical calculations. The influence of
molecular symmetry is studied by comparing Pc, Pc-d12, and Pc-d11. The spectra of
Pc-d12 show strong similarity to those of the parent undeuterated porphycene
(Pc). Comparable tunneling splitting is observed in the two isotopologues, both
for the 0-0 transition and the most efficient promoting 2Ag mode. In contrast, an
unusual isotopic effect is observed for the totally symmetrical 4Ag mode. While
this vibration behaves as a neutral mode in Pc, neither enhancing nor decreasing
the tunneling efficiency, it strongly promotes hydrogen transfer in Pc-d12. This
observation is explained in terms of modification of the displacement vectors of
the 4Ag mode upon deuteration. It demonstrates that isotope substitution affects
hydrogen transfer even when the weak structural modifications are far from the
reaction center, emphasizing the strongly multidimensional nature of the
tunneling process.
PMID- 25137227
TI - Structural and functional investigation of zebrafish (Danio rerio) NOD1 leucine
rich repeat domain and its interaction with iE-DAP.
AB - Nucleotide binding and oligomerization domain 1 (NOD1), a cytoplasmic pattern
recognition receptor (PRR) and is a key component for modulating innate immunity
and signaling. It is highly specific to gamma-D-Glu-mDAP (iE-DAP), a cell wall
component of Gram-negative and few Gram-positive bacteria. In the absence of the
experimental structure of NOD1 leucine rich repeat (NOD1-LRR) domain, the NOD
signaling cascade mediated through NOD1 and iE-DAP interaction is poorly
understood. Herein, we modeled 3D structure of zebrafish NOD1-LRR (zNOD1-LRR)
through a protein-threading approach and structural integrity of the model was
assessed using molecular dynamics simulations. Molecular interaction analysis of
iE-DAP and zNOD1-LRR, their complex stability and binding free energy studies
were conducted to anticipate the ligand binding residues in zNOD1. Our study
revealed that His775, Lys777, Asp803, Gly805, Trp807, Asn831, Ser833, Ile859 and
Trp861 situated in the beta-sheet region of zNOD1-LRR could be involved in iE-DAP
recognition, which correlates the earlier findings in human. Comparison of
binding free energies of native and mutant zNOD1-iE-DAP complexes delineated
His775, Lys777, Asp803, Ser833 and Ile859 as the pivotal residues for energetic
stability of NOD1 and iE-DAP interaction. This study provides the first
comprehensive description of biophysical and biochemical parameters responsible
for NOD1 and iE-DAP interaction in zebrafish, which is expected to shed more
light on NOD1 signaling and therapeutic applications in other organisms.
PMID- 25137230
TI - Magnetic susceptibility of uranium complexes.
PMID- 25137229
TI - Simple and validated quantitative 1H NMR method for the determination of
methylation, acetylation, and feruloylation degree of pectin.
AB - The knowledge of pectin esterification degree is of primary importance to predict
gelling and other properties of pectin from different sources. This paper reports
the development of a simple and rapid (1)H NMR-based method for the simultaneous
quantitative determination of methylation, acetylation, and feruloylation degree
of pectin isolated from various food sources. Pectin esters are hydrolyzed in
NaOH/D2O, and the obtained methanol, acetic acid, and ferulic acid are directly
measured by (1)H NMR. High accuracy, repeatability, and reproducibility of the
method were obtained, and the analysis time is reduced as compared to
conventional chromatography- or titration-based methods.
PMID- 25137231
TI - Uncommon cis configuration of a metal-metal bridging noninnocent Nindigo ligand.
AB - In contrast to several reported coordination compounds of trans-Nindigo ligands
[Nindigo = indigo-bis(N-arylimine) = LH2] with one or two six-membered chelate
rings involving one indole N and one extracyclic N for metal binding, the new
diruthenium complex ion [(acac)2Ru(MU,eta(2):eta(2)-L)Ru(bpy)2](2+) = 2(2+)
exhibits edge-sharing five- and seven-membered chelate rings in the first
documented case of asymmetric bridging by a Nindigo ligand in the cis
configuration [L(2-) = indigo-bis(N-phenylimine)dianion]. The dication in
compound [2](ClO4)2 displays one Ru(alpha-diimine)3 site and one ruthenium center
with three negatively charged chelate ligands. Compound [2](ClO4)2 is obtained
from the [Ru(bpy)2](2+)-containing cis precursor [(LH)Ru(bpy)2]ClO4 = [1]ClO4,
which exhibits intramolecular H-bonding in the cation. Four accessible oxidation
states each were characterized for the 1(n) and 2(n) redox series with respect to
metal- or ligand-centered electron transfer, based on X-ray structures, electron
paramagnetic resonance, and ultraviolet-visible-near-infrared
spectroelectrochemistry in conjunction with density functional theory calculation
results. The structural asymmetry in the Ru(III)/Ru(II) system 2(2+) is reflected
by the electronic asymmetry (class I mixed-valence situation), leaving the
noninnocent Nindigo bridge as the main redox-active site.
PMID- 25137225
TI - From pathways to networks: connecting dots by establishing protein-protein
interaction networks in signaling pathways using affinity purification and mass
spectrometry.
AB - Signal transductions are the basis of biological activities in all living
organisms. Studying the signaling pathways, especially under physiological
conditions, has become one of the most important facets of modern biological
research. During the last decade, MS has been used extensively in biological
research and is proven to be effective in addressing important biological
questions. Here, we review the current progress in the understanding of signaling
networks using MS approaches. We will focus on studies of protein-protein
interactions that use affinity purification followed by MS approach. We discuss
obstacles to affinity purification, data processing, functional validation, and
identification of transient interactions and provide potential solutions for
pathway-specific proteomics analysis, which we hope one day will lead to a
comprehensive understanding of signaling networks in humans.
PMID- 25137234
TI - A multiple relevance feedback strategy with positive and negative models.
AB - A commonly used strategy to improve search accuracy is through feedback
techniques. Most existing work on feedback relies on positive information, and
has been extensively studied in information retrieval. However, when a query
topic is difficult and the results from the first-pass retrieval are very poor,
it is impossible to extract enough useful terms from a few positive documents.
Therefore, the positive feedback strategy is incapable to improve retrieval in
this situation. Contrarily, there is a relatively large number of negative
documents in the top of the result list, and it has been confirmed that negative
feedback strategy is an important and useful way for adapting this scenario by
several recent studies. In this paper, we consider a scenario when the search
results are so poor that there are at most three relevant documents in the top
twenty documents. Then, we conduct a novel study of multiple strategies for
relevance feedback using both positive and negative examples from the first-pass
retrieval to improve retrieval accuracy for such difficult queries. Experimental
results on these TREC collections show that the proposed language model based
multiple model feedback method which is generally more effective than both the
baseline method and the methods using only positive or negative model.
PMID- 25137233
TI - The roles of cellular nanomechanics in cancer.
AB - The biomechanical properties of cells and tissues may be instrumental in
increasing our understanding of cellular behavior and cellular manifestations of
diseases such as cancer. Nanomechanical properties can offer clinical translation
of therapies beyond what are currently employed. Nanomechanical properties, often
measured by nanoindentation methods using atomic force microscopy, may identify
morphological variations, cellular binding forces, and surface adhesion behaviors
that efficiently differentiate normal cells and cancer cells. The aim of this
review is to examine current research involving the general use of atomic force
microscopy/nanoindentation in measuring cellular nanomechanics; various factors
and instrumental conditions that influence the nanomechanical properties of
cells; and implementation of nanoindentation methods to distinguish cancer cells
from normal cells or tissues. Applying these fundamental nanomechanical
properties to current discoveries in clinical treatment may result in greater
efficiency in diagnosis, treatment, and prevention of cancer, which ultimately
can change the lives of patients.
PMID- 25137238
TI - Fumigant methyl iodide can methylate inorganic mercury species in natural waters.
AB - Methyl iodide or iodomethane (CH3I) has recently been registered as a fumigant in
many countries, although its environmental impacts are not well understood. Here
we report the results of a study on the methylation of mercury by CH3I in natural
water by incubation experiments using both Hg ((199)HgCl2 and CH3(201)Hg(+))- and
hydrogen (CD3I)-stable isotope addition techniques. We find that methylation of
Hg(0), Hg2(2+) and Hg(2+) by CH3I can occur in natural water under sunlight,
while only Hg(0) and Hg2(2+) can be methylated in deionized water. We propose
that the methylation of Hg by CH3I in natural waters is mediated by sunlight and
involves two steps, the reduction of Hg(2+) to Hg(0)/Hg2(2+) and the subsequent
methylation of Hg(0)/Hg2(2+) by CH3I. Further quantitative assessment suggests
that CH3I-involved methylation of inorganic Hg could be an important source of
CH3Hg(+) in an environment where CH3I has been used in large amounts as a
fumigant.
PMID- 25137235
TI - Effect of dialysis initiation timing on clinical outcomes: a propensity-matched
analysis of a prospective cohort study in Korea.
AB - BACKGROUND: Controversy persists regarding the appropriate initiation timing of
renal replacement therapy for patients with end-stage renal disease. We evaluated
the effect of dialysis initiation timing on clinical outcomes. Initiation times
were classified according to glomerular filtration rate (GFR). METHODS: We
enrolled a total of 1691 adult patients who started dialysis between August 2008
and March 2013 in a multi-center, prospective cohort study at the Clinical
Research Center for End Stage Renal Disease in the Republic of Korea. The
patients were classified into the early-start group or the late-start group
according to the mean estimated GFR value, which was 7.37 ml/min/1.73 m2. The
primary outcome was patient survival, and the secondary outcomes were
hospitalization, cardiovascular events, vascular access complications, change of
dialysis modality, and peritonitis. The two groups were compared before and after
matching with propensity scores. RESULTS: Before propensity score matching, the
early-start group had a poor survival rate (P<0.001). Hospitalization,
cardiovascular events, vascular access complications, changes in dialysis
modality, and peritonitis were not different between the groups. A total of 854
patients (427 in each group) were selected by propensity score matching. After
matching, neither patient survival nor any of the other outcomes differed between
groups. CONCLUSIONS: There was no clinical benefit after adjustment by propensity
scores comparing early versus late initiation of dialysis.
PMID- 25137239
TI - Transportation optimization with fuzzy trapezoidal numbers based on possibility
theory.
AB - In this paper, a parametric method is introduced to solve fuzzy transportation
problem. Considering that parameters of transportation problem have
uncertainties, this paper develops a generalized fuzzy transportation problem
with fuzzy supply, demand and cost. For simplicity, these parameters are assumed
to be fuzzy trapezoidal numbers. Based on possibility theory and consistent with
decision-makers' subjectiveness and practical requirements, the fuzzy
transportation problem is transformed to a crisp linear transportation problem by
defuzzifying fuzzy constraints and objectives with application of fractile and
modality approach. Finally, a numerical example is provided to exemplify the
application of fuzzy transportation programming and to verify the validity of the
proposed methods.
PMID- 25137236
TI - Safety of hormonal replacement therapy and oral contraceptives in systemic lupus
erythematosus: a systematic review and meta-analysis.
AB - BACKGROUND: There is conflicting data regarding exogenous sex hormones [oral
contraceptives (OC) and hormonal replacement therapy (HRT)] exposure and
different outcomes on Systemic Lupus Erythematosus (SLE). The aim of this work is
to determine, through a systematic review and meta-analysis the risks associated
with estrogen use for women with SLE as well as the association of estrogen with
developing SLE. METHODS AND FINDINGS: MEDLINE, EMBASE, SciElo, BIREME and the
Cochrane library (1982 to July 2012), were databases from which were selected and
reviewed (PRISMA guidelines) randomized controlled trials, cross-sectional, case
control and prospective or retrospective nonrandomized, comparative studies
without language restrictions. Those were evaluated by two investigators who
extracted information on study characteristics, outcomes of interest, risk of
bias and summarized strength of evidence. A total of 6,879 articles were
identified; 20 full-text articles were included. Thirty-two meta-analyses were
developed. A significant association between HRT exposure (Random model) and an
increased risk of developing SLE was found (Rate Ratio: 1.96; 95%-CI: 1.51-2.56;
P-value<0.001). One of eleven meta-analyses evaluating the risk for SLE
associated with OC exposure had a marginally significant result. There were no
associations between HRT or OC exposure and specific outcomes of SLE. It was not
always possible to Meta-analyze all the available data. There was a wide
heterogeneity of SLE outcome measurements and estrogen therapy administration.
CONCLUSION: An association between HRT exposure and SLE causality was observed.
No association was found when analyzing the risk for SLE among OC users, however
since women with high disease activity/Thromboses or antiphospholipid-antibodies
were excluded from most of the studies, caution should be exercised in
interpreting the present results. To identify risk factors that predispose
healthy individuals to the development of SLE who are planning to start HRT or OC
is suggested.
PMID- 25137240
TI - Gender and age-related differences in bilateral lower extremity mechanics during
treadmill running.
AB - Female runners have a two-fold risk of sustaining certain running-related
injuries as compared to their male counterparts. Thus, a comprehensive
understanding of the sex-related differences in running kinematics is necessary.
However, previous studies have either used discrete time point variables and
inferential statistics and/or relatively small subject numbers. Therefore, the
first purpose of this study was to use a principal component analysis (PCA)
method along with a support vector machine (SVM) classifier to examine the
differences in running gait kinematics between female and male runners across a
large sample of the running population as well as between two age-specific sub
groups. Bilateral 3-dimensional lower extremity gait kinematic data were
collected during treadmill running. Data were analysed on the complete sample (n
= 483: female 263, male 220), a younger subject group (n = 56), and an older
subject group (n = 51). The PC scores were first sorted by the percentage of
variance explained and we also employed a novel approach wherein PCs were sorted
based on between-gender statistical effect sizes. An SVM was used to determine if
the sex and age conditions were separable and classifiable based on the PCA.
Forty PCs explained 84.74% of the variance in the data and an SVM classification
accuracy of 86.34% was found between female and male runners. Classification
accuracies between genders for younger subjects were higher than a subgroup of
older runners. The observed interactions between age and gender suggest these
factors must be considered together when trying to create homogenous sub-groups
for research purposes.
PMID- 25137241
TI - Droplet electrospray ionization mass spectrometry for high throughput screening
for enzyme inhibitors.
AB - High throughput screening (HTS) is important for identifying molecules with
desired properties. Mass spectrometry (MS) is potentially powerful for label-free
HTS due to its high sensitivity, speed, and resolution. Segmented flow, where
samples are manipulated as droplets separated by an immiscible fluid, is an
intriguing format for high throughput MS because it can be used to reliably and
precisely manipulate nanoliter volumes and can be directly coupled to
electrospray ionization (ESI) MS for rapid analysis. In this study, we describe a
"MS Plate Reader" that couples standard multiwell plate HTS workflow to droplet
ESI-MS. The MS plate reader can reformat 3072 samples from eight 384-well plates
into nanoliter droplets segmented by an immiscible oil at 4.5 samples/s and
sequentially analyze them by MS at 2 samples/s. Using the system, a label-free
screen for cathepsin B modulators against 1280 chemicals was completed in 45 min
with a high Z-factor (>0.72) and no false positives (24 of 24 hits confirmed).
The assay revealed 11 structures not previously linked to cathepsin inhibition.
For even larger scale screening, reformatting and analysis could be conducted
simultaneously, which would enable more than 145,000 samples to be analyzed in 1
day.
PMID- 25137242
TI - Isotopic studies of the diet of the people of the coast of British Columbia.
AB - In 1982, Chisholm et al. used delta(13) C data for human burials from shell
midden sites widely distributed on the coast of British Columbia (BC) to show the
extreme dependence of these individuals on high trophic level marine consumers,
principally salmon and marine mammals. Here, we present previously unpublished
analyses of delta(15) N for some of the same individuals as well as delta(13) C
data for additional individuals. Nitrogen isotope data show that the diet was
dominated by high trophic level marine fauna including carnivorous fish and
marine mammals. Although most burials were found in shell middens, marine
mollusks made up of only a minor component of diet. The data for delta(13) C
demonstrate that terrestrial faunal foods are undetectable in the diet of the
majority of individuals, and seldom constitute more than 10% of the dietary
protein of individuals living on the coast although terrestrial fauna were widely
available as a potential source of protein. This dietary pattern of exclusion of
land-based animals from their diet persisted for almost 6,000 years along a wide
expanse of coastline. In contrast, people from the BC interior (100 km or more
from the coast) consumed a mixed diet of terrestrial and marine foods including
spawning salmon.
PMID- 25137244
TI - Sex-specific relationships of physical activity, body composition, and muscle
quality with lower-extremity physical function in older men and women.
AB - OBJECTIVE: This study aims to determine the sex-specific relationships of
physical activity, body composition, and muscle quality with lower-extremity
physical function in older men and women. METHODS: Seventy-nine community
dwelling men (n = 39; mean [SD] age, 76.1 [6.2] y; mean [SD] body mass index,
27.3 [3.8] kg/m(2)) and women (n = 40; mean [SD] age, 75.8 [5.5] y; mean [SD]
body mass index, 27.0 [3.8] kg/m(2)) were assessed for physical activity via
questionnaire, body composition via dual-energy x-ray absorptiometry scanning,
leg extension power using the Nottingham power rig, and muscle quality (W/kg; the
ratio of leg extension power [W] to lower-body mineral-free lean mass [kg]). A
composite measure of physical function was obtained by summing Z scores from the
6-minute walk, 8-ft up-and-go test, and 30-second chair-stand test. RESULTS: As
expected, men had significantly greater levels of physical activity, lower
adiposity, greater lean mass, higher leg extension power, and greater muscle
quality compared with women (all P < 0.05). In linear regression analyses, muscle
quality and physical activity were the strongest predictors of lower-extremity
physical function in men and independently explained 42% and 29% of the variance,
respectively. In women, muscle quality (16%) and percent body fat (12%) were
independent predictors after adjustment for covariates. CONCLUSIONS: Muscle
quality is the strongest predictor of lower-extremity physical function in men
and women, but sex impacts the importance of physical activity and adiposity.
These findings suggest that older men and women may benefit from different
intervention strategies for preventing physical disability and also highlight the
importance of weight management for older women to preserve physical function.
PMID- 25137243
TI - Low-dose paroxetine (7.5 mg) improves sleep in women with vasomotor symptoms
associated with menopause.
AB - OBJECTIVE: Sleep disturbances are common among women in midlife; prevalence
increases among perimenopausal/postmenopausal women with vasomotor symptoms.
Paroxetine 7.5 mg is the only nonhormonal treatment that has been approved in the
United States for moderate to severe vasomotor symptoms associated with
menopause. In two pivotal phase 3 studies evaluating its efficacy and safety,
improvements in sleep disturbances were also prospectively evaluated. METHODS:
Postmenopausal women with moderate to severe vasomotor symptoms were randomly
assigned to paroxetine 7.5 mg (n = 591) or placebo (n = 593) once daily for 12
weeks (both studies) or 24 weeks (24-wk study). Predefined assessments on weeks
4, 12, and 24 included number of nighttime awakenings attributed to vasomotor
symptoms, sleep-onset latency, sleep duration, and sleep-related adverse events.
The two studies' data for weeks 1 to 12 were pooled. RESULTS: At baseline,
participants reported a mean of 3.6 awakenings/night attributed to vasomotor
symptoms. Nighttime awakenings attributed to vasomotor symptoms were
significantly reduced within 4 weeks of initiating paroxetine 7.5 mg treatment
(39% reduction vs 28% for placebo; P = 0.0049), and reductions were sustained
through 12 or 24 weeks of treatment. Paroxetine 7.5 mg treatment also
significantly increased nighttime sleep duration (week 4, +31 vs +16 min for
placebo; P = 0.0075), but no significant between-group differences in sleep-onset
latency or sleep-related adverse events such as sedation were observed.
CONCLUSIONS: In postmenopausal women treated for menopausal vasomotor symptoms,
paroxetine 7.5 mg significantly reduces the number of nighttime awakenings
attributed to vasomotor symptoms and increases sleep duration without
differentially affecting sleep-onset latency or sedation.
PMID- 25137245
TI - Feelings of energy are associated with physical activity and sleep quality, but
not adiposity, in middle-aged postmenopausal women.
AB - OBJECTIVE: Feelings of fatigue and low energy are widespread among middle-aged
women and have been shown to negatively affect quality of life. The aim of the
present study was to examine the associations among adiposity, physical activity,
and feelings of fatigue and energy in postmenopausal women. METHODS:
Postmenopausal women (N = 74; mean [SD] age, 58.9 [3.8] y) were assessed for
adiposity (via dual-energy x-ray absorptiometry), steps per day, minutes of
moderate to vigorous physical activity per day (via an accelerometer), prior week
intensity of psychological vigor (via the Profile of Mood States-Short Form), and
prior month frequency of energy feelings (via the vitality scale of the 36-item
Medical Outcomes Survey--Short Form). Sleep quality was measured using the
Pittsburgh Sleep Quality Index, depression was measured using the Beck Depression
Inventory-II, and perceived stress was measured using the Perceived Stress Scale.
RESULTS: Adiposity was negatively related to steps per day (r = -0.55, P < 0.05)
and minutes of moderate to vigorous physical activity per day (r = -0.48, P <
0.05). Adiposity was not significantly related to vigor, vitality, or any other
psychological measures. Greater vitality was associated with lower total number
of medications (r = -0.31, P < 0.01), more steps per day (r = 0.28, P < 0.05),
and higher minutes of moderate to vigorous physical activity per day (r = 0.37, P
< 0.01). Prior week feelings of vigor were unrelated to any variable of interest.
Regression analyses revealed that minutes of moderate to vigorous physical
activity per day independently explained 8% of the variance in vitality, whereas
sleep quality was also a significant predictor of vitality (both P < 0.05).
CONCLUSIONS: Engaging in recommended amounts of moderate to vigorous physical
activity per day is associated with higher monthly frequency of energy feelings,
regardless of adiposity status, in middle-aged postmenopausal women.
PMID- 25137248
TI - Theoretical study for OH radical-initiated atmospheric oxidation of ethyl
acrylate.
AB - OH radical-initiated atmospheric oxidation of ethyl acrylate (ethyl 2-propenoate,
EA) has been investigated by performing density functional theory (DFT)
calculations. Optimizations of the reactants, intermediates, transition states
and products were carried out at the MPWB1K/6-31+G(d,p) level. Single-point
energy calculations were performed at the MPWB1K/6-311+G(3df,2p) level of theory.
The detailed oxidation mechanism was presented and discussed. The results show
that the OH addition is more energetically favorable than the H abstraction. Rice
Ramsperger-Kassel-Marcus (RRKM) theory was used to predict the rate constants
over the possible atmospheric temperature range of 180-370 K. The Arrhenius
expression adequately describes the total rate constant: k(EA+OH)=(1.71*10(
12))exp(805.42/T)cm(3) molecule(-1) s(-1). At 298 K, the atmospheric lifetime of
ethyl acrylate determined by OH radicals is about 16.2h. In order to find out the
effect of alkyl substitution on the reaction activity, rate constants for the
reactions of methyl acrylate, methyl methacrylate and butyl acrylate with OH
radicals were also discussed. Calculation results show that the reaction activity
may increase with the increased electron-donating substitution for electrophilic
addition reaction.
PMID- 25137246
TI - Ethics, economics, and the use of primaquine to reduce falciparum malaria
transmission in asymptomatic populations.
AB - Yoel Lubell and colleagues consider ethical and economic perspectives on mass
drug administration of primaquine to limit transmission of P. falciparum malaria.
Please see later in the article for the Editors' Summary.
PMID- 25137249
TI - Preparation, anti-trypanosomal activity and localisation of a series of dipeptide
based vinyl sulfones.
AB - An improved, Weinreb amide-based, synthesis of anti-trypanosomal lysine
containing vinyl sulfones is described incorporating, as a feature, diversity at
the epsilon-lysine amino group. Members of this family demonstrated moderate to
good efficacy as anti-trypanosomal agents and a fluorescent dansyl (19)
derivative was used to investigate subcellular localisation of the compound
class.
PMID- 25137250
TI - Twisted intramolecular charge transfer and its contribution to the NLO activity
of Diglycine Picrate: a vibrational spectroscopic study.
AB - Single crystals of Diglycine Picrate (DGLP) were grown by slow evaporation
technique and the vibrational spectral analysis is carried out using FT Raman and
FT-IR spectroscopy, supported by Density Functional Theoretical (DFT)
computations to derive equilibrium geometry, vibrational wavenumbers and first
hyperpolarizability. The vibrational spectra confirm the existence of NH3(+) in
DGLP. The influence of Twisted Intramolecular Charge Transfer (TICT) caused by
the strong ionic ground state hydrogen bonding between charged species making
DGLP crystal to have the non-centrosymmetric structure has been discussed. The
Natural Bond Orbital (NBO) analysis confirms the occurrence of strong
intermolecular N-H?O hydrogen bond. The HOMO-LUMO energy gap and the first order
hyperpolarizability were calculated and it supports the nonlinear optical
activity of the Diglycine Picrate crystal.
PMID- 25137251
TI - Recombination blurs phylogenetic groups routine assignment in Escherichia coli:
setting the record straight.
AB - The characterization of population structures plays a main role for understanding
outbreaks and the dynamics of bacterial spreading. In Escherichia coli, the
widely used combination of multiplex-PCR scheme together with goeBURST has some
limitations. The purpose of this study is to show that the combination of
different phylogenetic approaches based on concatenated sequences of MLST genes
results in a more precise assignment of E. coli phylogenetic groups, complete
understanding of population structure and reconstruction of ancestral clones. A
collection of 80 Escherichia coli strains of different origins was analyzed
following the Clermont and Doumith's multiplex-PCR schemes. Doumith's multiplex
PCR showed only 1.7% of misassignment, whereas Clermont's-2000 protocol reached
14.0%, although the discrepancies reached 30% and 38.7% respectively when
recombinant C, F and E phylogroups were considered. Therefore, correct phylogroup
attribution is highly variable and depends on the clonal composition of the
sample. As far as population structure of these E. coli strains, including 48 E.
coli genomes from GenBank, goeBURST provides a quite dispersed population
structure; whereas NeighborNet approach reveals a complex population structure.
MLST-based eBURST can infer different founder genotypes, for instance ST23/ST88
could be detected as the founder genotypes for STC23; however, phylogenetic
reconstructions might suggest ST410 as the ancestor clone and several
evolutionary trajectories with different founders. To improve our routine
understanding of E. coli molecular epidemiology, we propose a strategy based on
three successive steps; first, to discriminate three main groups A/B1/C, D/F/E
and B2 following Doumith's protocol; second, visualization of population
structure based on MLST genes according to goeBURST, using NeighborNet to
establish more complex relationships among STs; and third, to perform, a cost
free characterization of evolutionary trajectories in variants emerging along the
clonal expansion using parsimony methods of phylogenetic analysis.
PMID- 25137252
TI - Thrombopoietin treatment of one graft in a double cord blood transplant provides
early platelet recovery while contributing to long-term engraftment in NSG mice.
AB - Human cord blood (CB) hematopoietic stem cell (HSC) transplants demonstrate
delayed early neutrophil and platelet recovery and delayed longer term immune
reconstitution compared to bone marrow and mobilized peripheral blood
transplants. Despite advances in enhancing early neutrophil engraftment, platelet
recovery after CB transplantation is not significantly altered when compared to
contemporaneous controls. Recent studies have identified a platelet-biased murine
HSC subset, maintained by thrombopoietin (TPO), which has enhanced capacity for
short- and long-term platelet reconstitution, can self-renew, and can give rise
to myeloid- and lymphoid-biased HSCs. In previous studies, we have shown that
transplantation of human CB CD34(+) cells precultured in TPO as a single graft
accelerates early platelet recovery as well as yielding long-term repopulation in
immune-deficient mice. In this study, using a double CB murine transplant model,
we investigated whether TPO cultured human CB CD34(+) cells have a competitive
advantage or disadvantage over untreated human CB CD34(+) cells in terms of (1)
short-term and longer term platelet recovery and (2) longer term hematological
recovery. Our studies demonstrate that the TPO treated graft shows accelerated
early platelet recovery without impairing the platelet engraftment of untreated
CD34(+) cells. Notably, this was followed by a dominant contribution to platelet
production through the untreated CD34(+) cell graft over the intermediate to
longer term. Furthermore, although the contribution of the TPO treated graft to
long-term hematological engraftment was reduced, the TPO treated and untreated
grafts both contributed significantly to long-term chimerism in vivo.
PMID- 25137253
TI - Does a no-take marine protected area benefit seahorses?
AB - Seahorses are iconic charismatic species that are often used to 'champion' marine
conservation causes around the world. As they are threatened in many countries by
over-exploitation and habitat loss, marine protected areas (MPAs) could help with
their protection and recovery. MPAs may conserve seahorses through protecting
essential habitats and removing fishing pressures. Populations of White's
seahorse, Hippocampus whitei, a species endemic to New South Wales, Australia,
were monitored monthly from 2006 to 2009 using diver surveys at two sites within
a no-take marine protected areas established in 1983, and at two control sites
outside the no-take MPA sites. Predators of H. whitei were also identified and
monitored. Hippocampus whitei were more abundant at the control sites. Seahorse
predators (3 species of fish and 2 species of octopus) were more abundant within
the no-take MPA sites. Seahorse and predator abundances were negatively
correlated. Substantial variability in the seahorse population at one of the
control sites reinforced the importance of long-term monitoring and use of
multiple control sites to assess the outcomes of MPAs for seahorses. MPAs should
be used cautiously to conserve seahorse populations as there is the risk of a
negative impact through increased predator abundance.
PMID- 25137254
TI - Chemical modulation of mutant mGlu1 receptors derived from deleterious GRM1
mutations found in schizophrenics.
AB - Schizophrenia is a complex and highly heterogeneous psychiatric disorder whose
precise etiology remains elusive. While genome-wide association studies (GWAS)
have identified risk genes, they have failed to determine if rare coding single
nucleotide polymorphisms (nsSNPs) contribute in schizophrenia. Recently, two
independent studies identified 12 rare, deleterious nsSNPS in the GRM1 gene,
which encodes the metabotropic glutamate receptor subtype 1 (mGlu1), in
schizophrenic patients. Here, we generated stable cell lines expressing the mGlu1
mutant receptors and assessed their pharmacology. Using both the endogenous
agonist glutamate and the synthetic agonist DHPG, we found that several of the
mutant mGlu1 receptors displayed a loss of function that was not due to a loss in
plasma membrane expression. Due to a lack of mGlu1 positive allosteric modulators
(PAM) tool compounds active at human mGlu1, we optimized a known mGlu4 PAM/mGlu1
NAM chemotype into a series of potent and selective mGlu1 PAMs by virtue of a
double "molecular switch". Employing mGlu1 PAMs from multiple chemotypes, we
demonstrate that the mutant receptors can be potentiated by small molecules and
in some cases efficacy restored to that comparable to wild type mGlu1 receptors,
suggesting deficits in patients with schizophrenia due to these mutations may be
amenable to intervention with an mGlu1 PAM. However, in wild type animals, mGlu1
negative allosteric modulators (NAMs) are efficacious in classic models
predictive of antipsychotic activity, whereas we show that mGlu1 PAMs have no
effect to slight potentiation in these models. These data further highlight the
heterogeneity of schizophrenia and the critical role of patient selection
strategies in psychiatric clinical trials to match genotype with therapeutic
mechanism.
PMID- 25137255
TI - Comparison of mercury contamination in live and dead dolphins from a newly
described species, Tursiops australis.
AB - Globally it is estimated that up to 37% of all marine mammals are at a risk of
extinction, due in particular to human impacts, including coastal pollution.
Dolphins are known to be at risk from anthropogenic contaminants due to their
longevity and high trophic position. While it is known that beach-cast animals
are often high in contaminants, it has not been possible to determine whether
levels may also be high in live animals from the same populations. In this paper
we quantitatively assess mercury contamination in the two main populations of a
newly described dolphin species from south eastern Australia, Tursiops australis.
This species appear to be limited to coastal waters in close proximity to a major
urban centre, and as such is likely to be vulnerable to anthropogenic pollution.
For the first time, we were able to compare blubber mercury concentrations from
biopsy samples of live individuals and necropsies of beach-cast animals and show
that beach-cast animals were highly contaminated with mercury, at almost three
times the levels found in live animals. Levels in live animals were also high,
and are attributable to chronic low dose exposure to mercury from the dolphin's
diet. Measurable levels of mercury were found in a number of important prey fish
species. This illustrates the potential for low dose toxins in the environment to
pass through marine food webs and potentially contribute to marine mammal deaths.
This study demonstrates the potential use of blubber from biopsy samples to make
inferences about the health of dolphins exposed to mercury.
PMID- 25137256
TI - Document of standardization of enteral nutrition access in adults.
AB - The group of standardization and protocols of the Spanish Society of Parenteral
and Enteral Nutrition (SENPE) published in 2011 a consensus document
SENPE/SEGHNP/ANECIPN/SECP on enteral access for paediatric nutritional support.
Along the lines of this document, we have developed another document on adult
patients to homogenize the clinical practice and improve the quality of care in
enteral access in this age group. The working group included health professionals
(nurses, dietitians and doctor) with extensive experience in enteral nutrition
and access. We tried to find scientific evidence through a literature review and
we used the criteria of the Agency for Health-care Research and Quality (AHRQ) to
classify the evidence (Grade of Recommendation A, B or C). Later the document was
reviewed by external experts to the group and requested the endorsement of the
Scientific and Educational Committee (CCE) and the group of home artificial
nutrition (NADYA) of the SENPE. The full text will be published as a monograph
number in this journal.
PMID- 25137257
TI - [Mobile applications for nutrition, dietetics and healthy habits; analysis and
consequences of an increasing trend].
AB - A mobile application or app, is a software designed for smartphones and other
mobile devices. Nowadays these have undergone a boom in its users offer and
diversity, entering the field of medicine, for both professionals and patients.
In "health apps" category, there is a part for the field of nutrition. It is
estimated that in the category of "diet and fitness" more than 5,400 apps. AIM:
Reviewing apps, to make a diagnosis of the quality and validity, and review
studies witch incorporating apps as part of the project s methodology. METHODS:
Literature search in major scientific databases, PubMed , SciELO , EMBASE (last 5
years) . In the other hand, a search was conducted in the Android APPs Store, 7
Key words were introduced in the form of APPs Sotre to analyze the top 5 of each
search. RESULTS: 95 Apps were analyzed, and others used from research studies.
The apps found to be an option as strategies for improvement and prevention of
certain diseases related to nutrition, exercise and daily habits, both from the
individual used or as professionals, but include the unreliability of the
majority. From the 95 apps analyzed, 51.57% were classified as "low quality".
CONCLUSION: Although most applications are not useful or safe, if in the future
are normalized and improved, they could provide a useful tool for the healthcare
system and society.
PMID- 25137258
TI - Hypertriglyceridemic waist phenotype: association with metabolic disorders and
visceral fat in adults.
AB - OBJECTIVE: To evaluate the association of Hypertriglyceridemic waist with
metabolic disorders and visceral fat in adults. METHODS: Cross-sectional study
with 191 individuals of both sexes. Subjects were grouped according to Waist
Circumference (WC) ratings (Men: > 90 cm; Women: > 80 cm) and triglycerides (TG)
(> 150 mg/dl) in Group 1 (HTW Phenotype): elevated WC and TG; Group 2 (absence of
HTW Phenotype): elevated WC and normal TG or normal WC and elevated TG or normal
WC and TG. Metabolic alternations, visceral adipose tissue (VAT) and
visceral/subcutaneous fat index (VF/SF) measured by computed tomography were
evaluated as cardiovascu - lar risk factors between the groups. RESULTS:
Individuals with HTW phenotype, 82% had three or more cardiovascular risk
factors. The association between cardiovascular risk factors with HTW phenotype
revealed that among men 73.7% had hypercholesterolemia, 94.9% elevated non-HDLc
and 78.9% excess of VAT area (p = 0.001). Among women, 65% had elevated Sistolic
Blood Plessure, 80% hypercholesterolemia and 90% elevated non-HDLc (p < 0.02).
CONCLUSION: The HTW phenotype associated with the metabolic alternations and VAT
excess. Individuals with HTW had higher number of cardiovascular risk factors.
The Hypertriglyceridemic waist can be used in clinical practice for investigating
cardiovascular risk and visceral adipose tissue in individuals.
PMID- 25137259
TI - Psychological well-being in a sample of obese patients compared with a control
group.
AB - INTRODUCTION: The literature has found that obese patients usually report more
depression and anxiety than normal weight individuals. However, not many
investigations have studied the relationship between obesity and quality of life
from a Positive Psychology approach. OBJECTIVE: In this study it is analyzed if
obese patients have less psychological well-being than a control group (normal
weight participants). METHOD: A total of 221 participants (111 obese individuals
and 110 controls) were selected to conduct the study. To measure psychological
well-being, the Spanish version of the Ryff's Scales was used. To measure mental
health, the Spanish version of the mental health component of the Short Form 36
Health Survey (SF-36) was used. RESULTS: It was found that obese participants
reported less psychological well-being than normal weight individuals, but that
there were not statistically significant differences in the case of mental health
measured with the SF-36. DISCUSSION: According to the results, it can be
concluded that reports of psychological well-being problems were much more common
in participants with weight problems than in the control group.
PMID- 25137260
TI - Beliefs, attitudes and phobias among Mexican medical and psychology students
towards people with obesity.
AB - BACKGROUND: A high prevalence of stigmatizing attitude among healthcare personnel
towards obese people has been reported. OBJECTIVE: To evaluate the beliefs,
attitudes and phobias that Mexican medical and psychology students have towards
obese people. METHODS: A cross-sectional study was conducted with 528 students
enrolled at the Autonomous University of Baja California in psychology and
medical schools. Weight, height and waist circumference were evaluated. Beliefs
about obesity were assessed with the BAOP scale, attitudes towards obese people
by the ATOP scale and obesity phobias by the F-scale. RESULTS: Participants
achieved a mean F-scale score of 3.4. Only seven per cent showed neutral or
positive attitudes towards obesity (<=?2.5). Less fat phobia was associated with
beliefs that obesity was not a result of the person's self-control (p = 0.0001)
and had better attitudes towards obese people (p = 0.0001). Men had higher risk
of fat phobia (OR = 1.5). CONCLUSIONS: High prevalence of phobias and negative
attitudes towards obesity was observed. Men had higher stigma.
PMID- 25137261
TI - Genome-wide screen of promoter methylation identifies novel markers in diet
induced obese mice.
AB - OBJECTIVE: To investigate the genome-wide promoter methylation and gene
expression for the identification of methylation markers in obesity. METHODS:
Using a high-fat, diet-induced obese mouse model, we performed comprehensive DNA
methylation profiling of gene promoters to determine the differentially
methylated genes using methylated DNA immunoprecipitation followed by
hybridization to the NimbleGen MM8 CpG plus Promoter Microarray. We further
integrated epigenomics data with gene expression profiling to identify promoters
exhibiting an association between methylation status and the expression of
downstream genes. RESULTS: A total of 24 hypermethylated promoters and 42
hypomethylated promoters in epididymal fat were selected as methylation markers,
which were associated with downregulated and upregulated gene expression,
respectively. The promoter methylation and differential gene expression of three
markers (Mmp2, Foxj3 and Ube2q2) in the fat were validated by sequencing
bisulfitemodified DNA and real-time reverse transcriptase PCR. The genes with
these differentially methylated promoters and the associated transcriptional
expression in the fat were primarily involved in biological activities in lipid
metabolism and storage, cellular differentiation, immunity and the pathogenesis
of obesity-related complications. CONCLUSIONS: This study represents the first
effort to determine methylation markers in obese mice that may regulate gene
transcription in obesity. Our approach has potential relevance for clinical
applications by identifying markers useful in elucidating the mechanisms of
obesity pathogenesis and its complications.
PMID- 25137262
TI - Short term low-calorie diet improves insulin sensitivity and metabolic parameters
in obese women.
AB - Obesity and insulin resistance are associated with an increase of cardiovascular
risk factors, including adipocytokines. The aim of this study was to investigate
the effect of low-calorie diet on serum lipids, adipokines, insulin resistance
and body composition in obese women. It was a clinical trial with class I obese
women aged 30-45 years submitted to hypocaloric diet for 90 days. Dietary intake,
anthropometric parameters, body composition, serum lipids, glucose, insulin,
leptin, adiponectin, HOMA-IR and QUICKI indexes were evaluated at the baseline,
30, 60 and 90 days. There was 30% significant decrease in energy intake, and also
decrease in body weight, body mass index and waist circumference (p < 0.01)
throughout the treatment period. Despite the amount of lean body mass (kg)
reduced in average, it was observed that lean body mass (%) had increased (p <
0.01) and that the amount of fat body mass (kg) had decreased significantly in
the third month (p < 0.05). Systolic blood pressure reduced up to -5mmHg (p <
0.05) after 90 days. Was observed a decrease (p < 0.05) on serum insulin and HOMA
IR until the 60th day, while the serum adiponectin increased (p < 0.01) during
treatment. Corroborating with the reduction of fat body mass and weight, serum
leptin also reduced (p < 0.01). These results suggest that the short-term low
calorie diet reduces total body fat, mainly found in the abdominal region, and
efficiently improve insulin sensitivity decreasing cardiovascular risk in obese
women.
PMID- 25137263
TI - The relationship between dental caries and obesity among primary school children
aged 5 to 14 years.
AB - BACKGROUND: Previous study revealed that the link between dental caries and
obesity has been controversial. The purpose of this research is to investigate
the association between dental caries and obesity among primary school children
in Wannan area, China. METHODS: A cross-sectional study was designed to collect
the routine health screening data for primary school children aged 5-14 years in
Wannan area,China, Overweight and obesity status were determined using the
International Obesity Task Force standard (IOTF) BMI cut-off points. Caries
status was recorded based on WHO recommendations. RESULTS: Our results revealed
that the overall caries prevalence of the subjects was 44.9%, Maximum number of
caries affected children belonged to underweight and normal group, followed by
overweight, and the least number was obesity. These differences were
statistically significant (chi-square test, P < 0.001). Children with obesity
were 1.908 times (OR =1.908; CI95%=1.750, 2.079) more likely have caries than
children with underweight or health weight. Overweight children were 1.547 times
(OR = 1.547; CI95% = 1.479, 1.618) more likely to have caries than children with
underweight or health weight. After adjusted the gender and age, a statistically
significant association was also observed between body mass index categories and
caries. CONCLUSIONS: Obesity may have a significant effect on caries prevalence
of primary school children in Wannan area, China. The importance of obesity
should not only be emphasized with respect to general diseases but also with
regard to carious lesions.
PMID- 25137264
TI - Association between nutritional status, C-reactive protein, adiponectin and HOMA
AD in Brazilian children.
AB - INTRODUCTION: In children, the presence of obesity is a major risk factor for the
occurrence of cardiovascular diseases on the adulthood. OBJECTIVE: To evaluate
the association of anthropometry, body composition, clinical variables and
biochemical profile with C-reactive protein and adiponectin levels, and insulin
resistance in children in the municipality of Nova Era, Brazil. METHODS: Nested
case-control study following a crosssectional study. We evaluated 178 children,
57 of them classified as obese and 121 as normal-weight from a population of 1024
schoolchildren 6 to 10 years old: Blood samples were collected after 12-hour fast
to obtain serum and plasma. We collected anthropometric and body composition
measures, systolic and diastolic blood pressure data. Sexual maturation was
assessed according to the stage of sexual development. We performed Student's t
test, Mann-Whitney U test, Pearson's correlation, Spearman's test and multiple
linear regression analysis. Independent variables with p < 0.05 were included in
the multiple regression model. Residual analysis was performed to assess model
validity. RESULTS: Among obese children, C-reactive protein levels were
associated with triacylglycerol levels and body fat percentage estimated by
skinfold thickness (R2 adjusted = 27.6%, p < 0.001). Adiponectin was associated
with HOMA-IR, HOMAAD and body fat percentage estimated by skinfold thickness (R2
adjusted = 75.5%, p < 0.001). HOMA-AD index was associated with HOMA-IR,
adiponectin, systolic blood pressure and weight (R2 adjusted = 90.7%, p < 0.001).
CONCLUSION: Significant associations were found between body composition,
anthropometry, clinical variables, biochemical profile and adiponectin and C
reactive protein levels and insulin resistance in obese and normal-weight
children.
PMID- 25137265
TI - Common variants in genes related to lipid and energy metabolism are associated
with weight loss after an intervention in overweight/obese adolescents.
AB - BACKGROUND: Some SNPs related to lipid and energy metabolism may be implicated
not only in the development of obesity and associated comorbidities, but also in
the weight loss response after a nutritional intervention. OBJECTIVE: In this
context, the present study analyzed four SNPs located within four genes known to
be associated with obesity and other obesity-related complications, and their
putative role in a weight-loss intervention in overweight/obese adolescents.
METHODS: The study population consisted of 199 overweight/obese adolescents (13
16 yr old) undergoing 10 weeks of a weight loss multidisciplinary intervention:
the EVASYON programme (www.estudioevasyon.org). Adolescents were genotyped for 4
SNPs, and anthropometric measurements and biochemical markers were analyzed at
the beginning and after the intervention. RESULTS: Interestingly, APOA5(rs662799)
was associated with the baseline anthropometric and biochemical outcomes, whereas
FTO (rs9939609) seemed to be related with the change of these values after the 10
week intervention. The other two SNPs, located in the CETP (rs1800777) and the
APOA1 (rs670) genes, showed important relationships with adiposity markers.
Specifically, a combined model including both SNPs turned up to explain up to 24%
of BMI-SDS change after 10 weeks of the multidisciplinary intervention, which may
contribute to under - stand the weight loss response. CONCLUSION: Common variants
in genes related to lipid and energy metabolism may influence not only
biochemical outcomes but also weight loss response after a multidisciplinary
intervention carried out in obese/overweight adolescents..
PMID- 25137266
TI - Finding new solutions in pediatric parenteral admixtures: how to improve quality
and to deal with shortages.
AB - INTRODUCTION: Pediatric parenteral nutrition enables normal growth even of
preterm infants. Those children require, however, tailored parenteral nutrition
and the creation of such can be challenging due to the risk of instability and
shortages. OBJECTIVE: Prototypical parenteral admixtures were created using
different calcium salts (organic and inorganic) and different lipid emulsions and
tested for stability. 36 of parenteral admixtures containing two types of calcium
salts: chloride or gluconolactobionate and different lipid emulsions
(SMOFlipid(r) or Lipofundin MCT/LCT(r)) were under investigation. METHODS:
Preliminary admixtures were prepared in two-chamber bags whereas lipid emulsions
were placed separately in the second chamber. Pre-admixtures were stored for up
to 21 days at +4oC. Contents of the two chambers were combined at t = 0 or after
21 days of storage. Physical analysis of completed admixtures (visual inspection,
microscopic observation, pH measurement and determination of the size
distribution of oily droplets) was carried out after 21 days of the storage.
Stability of lipid, commercial emulsions stored in ethylene vinyl acetate (EVA)
bags for 42 days was also studied. RESULTS: Irrespectively of the time of storage
of preadmixtures and type of calcium salt and different lipid emulsions among 36
total parenteral admixtures only one showed signs of destabilization after
preparation and one was unstable when stored for longer than 14 days. All other
formulations were qualified to be stable during the study. All investigated
commercial lipid emulsions were physically stable in EVA bags even when stored at
room temperature. CONCLUSION: The study proved that it was possible to store pre
admixture in EVA bags for 21 days at 4 degrees C as well as that CAN (critical
aggregation number) and CaxP (the products of multiplication of calcium and
phosphate ions concentration) should not be used as reliable indicators of
admixture physical stability. No influence of the type of calcium salts on
stability of admixtures was observed.
PMID- 25137267
TI - Effect of long-term physical exercise program and/or diet on metabolic syndrome
in obese boys.
AB - INTRODUCTION: There have been just a few studies examining the influence of
detraining on obese boys. They conclude that any gains regress to the untrained
control values during the detraining period. OBJECTIVE: The objective of the
present study was thus to evaluate the effects of detraining (6 months) on
metabolic syndrome after two types of intervention (both 31 months), one of an
exercise program alone and the other of a diet-plus-exercise program, in obese
boys. METHODS: The participants were 18 sedentary boys (8- 11 years old) with a
body mass index equal or greater than the 97th percentile for the age and sex
(male) of the subject, without any dysfunction or metabolic problem. The
participants were divided into two groups - the E group (physical exercise
program) and the E+D group (physical exercise program plus a low calorie diet).
Metabolic parameters were evaluated (TC, HDL, LDL, TG, glucose, insulin, Systolic
Blood Pressure, and Diastolic Blood Pressure), allowing the metabolic syndrome
index to be calculated. RESULTS: Changes were observed in LDL-C (effect sizes =
3.19 and -2.28) and in the LDL-C/HDL-C ratio (effect sizes = -3.02 and -1.16) in
the E and E+D groups, respectively. The prevalence of metabolic syndrome and
obesity was completely removed only in the E group (100% norisk and non-obese
subjects - < 90th percentile). CONCLUSIONS: Detraining from a long-term exercise
program (with or without diet) seems not to negatively affect the cardiovascular
profile, suggesting that the program provides benefits and fosters healthy habits
that can be maintained over time, preventing the development of metabolic
syndrome.
PMID- 25137268
TI - [Sensory evaluation of enteral nutritional supplements].
AB - INTRODUCTION AND OBJECTIVES: Enteral nutrition (EN) is indicated in patients who,
although they may not eat enough food, maintain a sufficient function to receive,
digest and absorb nutrients digestive system. Oral Nutritional Supplements (SON)
are nutritionally complete or incomplete formulas (depending on whether or not
provide all the nutrients needed to serve as the sole source of nutrients), which
supplement inadequate oral diet. This study aims to evaluate the organoleptic
characteristics of hyperproteic, normoproteic and fiber-enriched oral SON.
MATERIAL AND METHODS: SON test, carried out at the Department of Endocrinology
and Nutrition Consortium Hospital General Universitario de Valencia from October
2012 to February 2013. 137 SON were evaluated in total, of which 47 were
hyperproteic, 46 normoproteic and 44 enriched in fiber. RESULTS: Of the SON
evaluated in the group of hyperproteic the following 3 SON obtained the best
scores: Fresenius Prot Energy Drink(r) (21,27, vanilla flavor), Avant Standard
Nut(r) (20.3 , strawberry flavor) and Resource(r) Protein (20.01, chocolate
flavor) In the group of normoproteic SON the 3 best rated were: Ensure Plus(r)
(22.3, banana flavor), Ensure Plus(r) (21.9, peach flavor) and Fresubin Energy
Drink(r) (21, strawberry flavor) In the group of fiber-enriched the 3 SON most
appreciated were: 2 Kcal Fresubin Fibre Drink(r) (23.78, vanilla flavor), Ensure
Plus(r) TwoCal (22.9, banana flavor) and Fortimel Compact(r) (21.5, strawberry
flavor) CONCLUSIONS: The study aims to guide clinicians on what SON may be more
acceptable to the patient, so that the SON serve their purpose and restore or
improve nutritional status, as the SON intervention is safe and cost - effective,
since they improve both the functionality and quality of life.
PMID- 25137269
TI - [Anti-inflammatory activity of olive seed polyphenolic extract in the THP1-XBLUE
CD14 human monocytes cell line].
AB - The aim of this study was to assess the anti-inflammatory activity of a
polyphenolic extract from olive pits. MATERIAL AND METHODS: The THP1-XBlue-CD14
(invivogen) cellular line, 80,000 cells/well, was incubated and inflammation
(activation of NF-kb) was produced with 0.1 mg/mL of LPS (lipopolysaccharide from
E. coli) for 24 hours. We assessed the presence of the extract (10 and 50 mg/L,
biologically safe concentrations) for 2 hours at 37o C, before (preventive
effect) and after (therapeutic effect) the proinflammatory activation, and the
activity of alkaline phosphatase, which is expressed under the control of the NF
kb transcriptional factor, was quantified by colorimetry. The percentage of
activity of NF-kb as preventive effect and therapeutic effect was assessed by
comparing it to control cultures of cells with LPS and without extract, which are
considered 100% of NF-kb. RESULTS: The preventive anti-inflammatory capacity of
the extract at 50 mg/L was 25.5% (95% CI: 16.8-34.2) and the therapeutic effect
34.9% (95% CI: 25.3-44.4) for the same concentration, without any significant
activity at 10 mg/L. CONCLUSION: An activity of polyphenols extracted from olive
pits is shown, both in preventing inflammation and therapeutically eliminating
inflammation through inhibition of NF-kB factor previously activated by LPS at
concentrations of 50 mg/L of polyphenols, which previously haven been shown to be
safe.
PMID- 25137270
TI - Fat-soluble vitamin deficiencies after bariatric surgery could be misleading if
they are not appropriately adjusted.
AB - OBJECTIVE: To evaluate the differences in frequency of fat-soluble vitamin
deficiencies if we adjust their levels by its main carriers in plasma in patients
undergoing Biliopancreatic diversion (BPD) and Roux-en-Y gastric bypass (RYGB).
RESEARCH METHODS & PROCEDURES: We recruited 178 patients who underwent RYGB (n =
116 patients) and BPD (n = 62 patients) in a single centre. Basal data
information and one-year after surgery included: anthropometric measurements, fat
soluble vitamins A, E and D, retinol binding protein (RBP) and total cholesterol
as carriers of vitamin A and E respectively. Continuous data were compared using
T-Student and proportions using chisquare test. RESULTS: There was a vitamin D
deficiency of 96% of all patients, 10% vitamin A deficiency and 1.2% vitamin E
deficiency prior to surgery. One year after surgery, 33% of patients were vitamin
A deficient but the frequency reduced to 19% when we adjusted by RBP. We found a
vitamin E deficiency frequency of 0% in RYGB and 4.8% in DBP one year after
surgery. However, when we adjusted the serum levels to total cholesterol, we
found an increased frequency of 8.7% in RYGB group for vitamin E deficiency and
21.4% in DBP (p = 0.04). CONCLUSION: We have found a different frequency of
deficit for fat-soluble vitamin both in BPD and RYGB once we have adjusted for
its main carriers. This is clinically relevant to prevent from overexposure and
toxicity. We suggest that carrier molecules should be routinely requested when we
assess fat-soluble vitamin status in patients who undergo malabsorptive
procedures.
PMID- 25137271
TI - High prevalence of vitamin D insufficiency among elite Spanish athletes the
importance of outdoor training adaptation.
AB - INTRODUCTION: The discovery of vitamin D muscle receptors in the last few years
suggested a significant role in muscle tissue, pointing out athletes as a special
group. Specific data are scarce. AIM: The main aim of the current paper was to
provide, for the first time, comparable data about vitamin D status in elite
Spanish athletes by sport, age, season and training environment. METHODS: Four
hundred and eight elite athletes with a mean age of 22.8 +/- 8.4 years were
recruited from the High-performance sport centre in Barcelona for this cross
sectional study. Athletes from 34 different sports modalities were analysed. Data
were available for vitamin D status, training environment, seasonality and number
of medical visits. All data were analysed using SPSS version 18.0. RESULTS: Mean
25(OH)D of all athletes was 56.7 +/- 23.4 nmol/L. Approximately 82% of the
athletes were below the optimal levels, (< 75nmol/l), 45% had moderate deficient
levels (< 50 nmol/L) and 6% had severe deficiency (< 27.5 nmol/L). We have
observed a steady increase in 25(OH)D concentrations with increasing age (p <
0.01) Highest levels were observed in those subjects training outdoors compared
with those training indoor (p.
PMID- 25137272
TI - [Evaluation of a nutritional intervention among elderly people: the Edumay
project].
AB - BACKGROUND: The adherence to a Mediterranean Dietary Pattern is associated with a
morbi-mortality reduction, and with a better quality of life. OBJECTIVES: To
evaluate a nutritional intervention among independent elderly people enrolled in
an educational program to increase the knowledge of the food and daily diets,
promoting a healthy dietary pattern. METHODS: Quasi-experimental design conducted
in elderly participants who lived in foster home apartments owned by the City
Council of Pamplona (n = 41). The intervention was based on six group sessions
and an individual motivational session in a period of three months. Adherence to
Mediterranean diet was evaluated through a 14-point scale previously validated.
RESULTS: Eighty point five per cent of participants were women, with a median age
of 79 years, the majority of them widowed (48.8%) and with primary education
(58.5%). After the nutritional intervention the percentage of participants who
consumed two or more servings of vegetables increased significantly versus the
control group (p = 0.042). Similarly, in comparison with the control group, there
was an increase in the percentage of participants who consumed three servings per
week of legumes (p = 0.042), three or more servings per week of nuts (p = 0.003),
and those who consumed preferably meat from chicken, turkey, or rabbit instead of
veal, pork, hamburgers, or sausages (p = 0.011). DISCUSSION: An intervention
based on individual and group sessions improved significantly several parameters
of a Mediterranean dietary pattern.
PMID- 25137273
TI - The influence of nutritional status and disease on adiponectin and TNF-alpha;
levels in colorectal cancer patients.
AB - BACKGROUND: The aim of this study was to evaluate the association between
adiponectin and tumor necrosis factor-alpha;?(TNF-alpha;) serum levels in
colorectal cancer (CRC) patients and compare these levels to clinical stage and
nutritional status. METHODS: A total of 79 patients were enrolled in the study
(39 with CRC and 40 in the control). Nutritional status was assessed by Patient
Generated Subjective Global Assessment (PG-SGA), body mass index (BMI), and phase
angle (PhA). Adiponectin and TNF-alpha;?serum concentrations were determined
using an enzyme-linked immunosorbent assay. RESULTS: Serum adiponectin levels
were higher among CRC patients (p = 0.001). TNF-alpha;?serum levels were not
significantly different between the groups, but patients with stage III or IV CRC
had higher levels of TNF-alpha;?than those with lower stage disease (p = 0.037).
The three tools used for the assessment of nutritional status (BMI, PhA, and PG
SGA) demonstrated that patients with a more severe nutritional deficit had higher
adipocytokine levels, although these differences were significant only to TNF- ?,
when distributed PhA in tertiles. CONCLUSIONS: Adiponectin levels were higher
among CRC patients. Although TNF-alpha;?serum levels from CRC patients did not
differ significantly to the control group, CRC patients with stage III or IV had
higher levels compared to those with stage I and II tumors. Nutritional status,
as determined by BMI, PhA, and PG-SGA, demonstrated that patients with a greatest
nutritional deficit, had higher levels of adipocytokines; however, these
differences were significant only for TNF-?, when distributed PhA in tertiles.
PMID- 25137274
TI - [Pilot study about the effectivity of an intervention based on games in
nutritional status and muscle strength on children].
AB - INTRODUCTION: The overnutrition is a constant on developing countries; Chile is
not an exception because it has a marked tendency to overweight and obesity in
schoolchildren. The muscular strength has been associated with cardiovascular and
metabolic health status in scholars. Effective interventions using games are
needed to improve the nutritional status and physical fitness in school children.
OBJECTIVE: To assess the intervention effectiveness based on games played at
school time to improve the nutritional status and physical fitness in
schoolchildren. METHOD: 156 students aged between 7 to 15 years, attending to two
public schools with full school day, to which a pilot program was applied. This
pilot program was based on dynamic recreational games during 45 minutes from
monday to friday for 3 months in the largest playtime of the school day. RESULTS:
At the end of the intervention, we observed a significant modification on
children nutritional status, which highlights an increase in the number of
children that reached the normal nutritional status (p < 0.001). We also observed
a significant number of obese children who reached overweight nutritional status
(p < 0.001). We also observed a decrease of leg muscular strength at the end of
the study. CONCLUSIONS: We found a positive effect of a program based on dynamic
recreational games in the largest school playtime, improving nutritional status.
However, we didn't observed modifications in the muscular strength.
PMID- 25137275
TI - [Design and validation of a questionnaire to assess dietary behavior in Mexican
students in the area of health].
AB - INTRODUCTION: The dietary behavior (DB) establishes the relationship between the
human being and foods and has an influence on nutrient intake and, therefore, it
contributes to the health or disease status of a population, even among college
students. There exit some validated instruments to assess food and nutrients
intake, but there are very few assessing DB. OBJECTIVE: To design and validate a
questionnaire to assess DB in Mexican college students. METHODS: According to the
literature and Reasoned Theory, a questionnaire assessing DB was designed. Its
logic and content validity was determined by expert assessment. It was applied on
two occasions with a 4-week interval to 333 students from the University of
Guadalajara coursing the sixth semester of Medicine or Nutrition. The
reproducibility was assessed by means of the interclass correlation coefficient.
The construct validity and the internal consistency were calculated by Rasch
analysis, for both the difficulty of the items and the subjects' capability.
RESULTS: The questionnaire finally included 31 questions with multiple choice
answers. The interclass correlation coefficient of the instrument was 0.76. The
Cronbach alpha was 0.50 for the subjects' capability and 0.98 for the internal
consistency of the items. 87.1% of the subjects and 89.8% of the items had INFIT
and OUTFIT values within acceptable limits. CONCLUSIONS: The present
questionnaire has the potentiality of measuring at low cost and in a practical
way aspects related with DB in college student with the aim of establishing or
following-up corrective or preventive actions.
PMID- 25137276
TI - Adherence to the Mediterranean diet by nursing students of Murcia (Spain).
AB - INTRODUCTION: The Mediterranean diet is recognized as one with the healthiest
dietary patterns; however, this diet is deteriorating and being abandoned even in
the Mediterranean countries themselves. Generally speaking, dietary habits get
fixed during adolescence although during the college phase, students may
experience important changes in their lifestyles. The KIDMED index is recognized
as a good tool to assess adherence to the Mediterranean diet (AMD). OBJECTIVE:
The aim of this study was to assess AMD in college students and to evidence
possible variations throughout the college period assessing differences between
the college years. METHOD: A cross-sectional study with 213 alumni in first grade
and 105 in fourth grade was carried out. The students were classified by gender,
type of residence (parents' home or out of the parents' house) and body mass
index (BMI) (< 25 or > 25). RESULTS: The BMI for the whole sample was 24.35 +/-
2.71 in men and 22.54 +/- 3.25 in women (p < 0.001). The mean score in AMD was
7.0 +/- 1.9, with 43% of the students showing good adherence. In general, a low
intake of fruits, vegetables, rice or pasta was observed, foods that are included
in the base of the dietary pyramid. Consumption of olive oil and legumes was very
high and a direct relationship was observed between overweighed people (BMI > 25)
and the habit of not having breakfast usually. No significant differences were
observed between the student of first and fourth grades although those students
in the fourth grade living away from the parental house had higher AMD level than
the other students (p < 0.001). CONCLUSIONS: Educational programs promoting the
intake of the different groups of food are recommended, was well as strategies
promoting the consumption of fruits and vegetables within the university area and
the healthy habit of having breakfast.
PMID- 25137277
TI - [Prevalence of nutritional risk evaluated with NRS-2002 in Mexican oncology
population].
AB - OBJECTIVE: Hospitalized patients have high risk of malnutrition, specially those
with cancer. There are some screening tools that lead to the detection of
malnutrition in hospitalized patients, as Nutritional Risk Screening 2002 (NRS
2002), which we used in Mexican population with cancer at the moment of hospital
admission to determine the prevalence of malnutrition risk, and to determine as
well as the best predictive item to measuring nutritional risk in our population.
METHODOLOGY: Nutritional status in cancer patients with NRS 2002 during hospital
admission was assessed. To the analysis of variable non statistical parametric
tests, student-t test, Pearson and Spearman test, as well as ANOVA test were
used. To determine the best item for predicting nutritional risk in Mexican
population with cancer, a logistic regression test was applied. RESULTS: Of our
population, 50.2% of were classified as patients in nutritional risk at hospital
admission. Gender, age, normal levels of IMC lower than 20.5, food intake, weight
loss and hematological cancer were associated with nutritional risk (p < 0.05).
The best model of logistic regression for predicting nutritional risk were the
same used by NRS-2002 questionnaire (p < 0.05). CONCLUSION: Malnutrition
prevalence is high in cancer patients and NRS-2002 is a reliable tool for
predicting nutritional risk in Mexican population with cancer.
PMID- 25137278
TI - [Body composition and heart rate variability in patients with chronic obstructive
pulmonary disease pulmonary rehabilitation candidates].
AB - Body composition is a non-invasive method, which gives us information about the
distribution of tissues in the body structure, it is also an indicator of the
risk of mortality in patients with chronic obstructive pulmonary disease. The
heart rate variability is a technique that gives us information of autonomic
physiological condition, being recognized as an indicator which is decreased in a
number of diseases. The purpose of this study was to assess body composition and
heart rate variability. The methodology used is that of Debora Kerr (1988)
endorsed by the International Society for advances in Cineantropometria for body
composition and heart rate variability of the guidelines described by the
American Heart Association (1996). Roscraff equipment, caliper Slimguide and
watch Polar RS 800CX was used. , BMI 26.7 +/- 3.9 kg / m2; Muscle Mass 26.1 +/-
6.3 kg ; Bone Mass 1.3 kg +/- 8.1 76 +/- 9.9 years Age : 14 candidates for
pulmonary rehabilitation patients were evaluated , Adipose mass 16.4 +/- 3.6 kg ;
FEV1 54 +/- 14%. Increased waist circumference and waist hip ratio was associated
with a lower overall heart rate variability. The bone component was positively
related to the variability of heart rate and patients with higher forced
expiratory volume in one second had lower high frequency component in heart rate
variability. In these patients, the heart rate variability is reduced globally
and is associated with cardiovascular risk parameters.
PMID- 25137279
TI - Hypomagnesaemia in critically ill patients with haematological malignancies.
AB - INTRODUCTION: There is currently little information regarding the incidence of
hypomagnesaemia and its impact on the prognosis of critically ill patients with
haematological malignancies. OBJECTIVE: This study sought to describe the
incidence of hypomagnesaemia in critically ill patients with haematological
malignancies admitted to an oncological intensive care unit (ICU). METHODS: A
total of 102 critically ill patients with haematological malignancies, who were
18 years of age and admitted to the ICU between January 2008 and April 2011, were
included in this study. Hypomagnesaemia was defined as a serum magnesium
concentration below 1.7 mg/dl. RESULTS: The incidence of hypomagnesaemia at
admission or during the first 24 hours of stay in the ICU was 22.5% (23/102). The
hospital mortality rates of patients with and without hypomagnesaemia were 47.8%
and 60.7%, respectively. CONCLUSION: The incidence of hypomagnesaemia in
critically ill patients with haematological malignancies was 22.5%. Mortality in
the ICU and in the hospital was similar in patients with and without
hypomagnesaemia.
PMID- 25137280
TI - The calcium concentration of public drinking waters and bottled mineral waters in
Spain and its contribution to satisfying nutritional needs.
AB - INTRODUCTION: A sufficient intake of calcium enables correct bone mineralization.
The bioavailability of calcium in water is similar to that in milk. OBJECTIVE: To
determine the concentration of calcium in public drinking water and bottled
mineral water. METHODS: We used ion chromatography to analyse the calcium
concentrations of public drinking waters in a representative sample of 108
Spanish municipalities (21,290,707 people) and of 109 natural mineral waters sold
in Spain, 97 of which were produced in Spain and 12 of which were imported.
RESULTS: The average calcium concentration of public drinking waters was 38.96 +/
32.44 mg/L (range: 0.40- 159.68 mg/L). In 27 municipalities, the water contained
50-100 mg/L of calcium and in six municipalities it contained over 100 mg/L. The
average calcium concentration of the 97 Spanish natural mineral water brands was
39.6 mg/L (range: 0.6-610.1 mg/L). Of these, 34 contained 50-100 mg/L of calcium
and six contained over 100 mg/L. Of the 12 imported brands, 10 contained over 50
mg/L. Assuming water consumption is as recommended, water containing 50-100 mg/L
of calcium provides 5.4-12.8% of the recommended intake of calcium for children
aged one to thirteen, up to 13.6% for adolescents, 5.8-17.6% for adults, and up
to 20.8% for lactating mothers. Water with 100-150 mg/L of calcium provides 10
31% of the recommended dietary allowance, depending on the age of the individual.
DISCUSSION: Public drinking water and natural mineral water consumption in a
third of Spanish cities can be considered an important complementary source of
calcium.
PMID- 25137281
TI - There is chronic latent magnesium deficiency in apparently healthy university
students.
AB - INTRODUCTION: Magnesium is an essential micronutrient for human body, and its
deficiency has been associated with risk of non-communicable diseases. OBJECTIVE:
Assessment of magnesium status, and evaluation of the frequency of magnesium
deficiency in a group of healthy adults. METHODS: Plasma and erythrocyte
magnesium levels, and magnesium intake were determined in 115 students (55 women
and 60 men), from a public university in Brazil. RESULTS: The medians of
magnesium concentration in plasma (0.76 mmol/L), erythrocyte (1.97 mmol/L), and
of dietary daily intake (8.84 mmol/d) were low. Forty two percent of participants
had plasma or erythrocyte magnesium below the limit of 0.75 and 1.65 mmol/L,
respectively. A high percentage showed high probability of inadequate magnesium
intake. CONCLUSIONS: There was a high frequency of subclinical magnesium
deficiency in the adults assessed, that could be related to low dietary magnesium
intake.
PMID- 25137283
TI - [Analysis of food service and opinion of its users in a Catalan prison].
AB - INTRODUCTION: Studies on food services are increasing actually in Spain. However,
there still is very little information on how this service is organized in
prisons, and even less about how it is perceived by its residents. OBJECTIVES: To
analyze the food service and menu in the Modelo Prison in Barcelona, and confront
it with the perception of prisoners. METHODS: Semi-structured open interview with
an official of the Division of Prisons, participant observation in the dining
room and other spaces by one of the study researchers, and a specifically
designed questionnaire adapted to this kind of institution. Nutrition and menu
quality assessment was performed using the DIAL program and healthy eating index
(IAS). RESULTS: The supplied menus usually contain an excess of fat (41.3%) and
carbohydrate deficit (41.7 %) even if is acceptable under IAS score (58.4
points). 75% of residents uses the dining room for daily main meals, spending
less than 15 minutes on average per meal. The space is considered very noisy. The
portions are considered adequate, but the taste, quality and service of food are
negatively valued. DISCUSSION AND CONCLUSIONS: Some gaps between institutional
proposals and everyday practices and perceptions of users are clearly denoted.
Some changes in food and dishes served in the menus -such as reducing meat and
increasing consumption of legumes- could contribute to improve nutrition,
perception and final cost of the menu. A greater variety of food and more
possibility of choice in the dining room and in the shop could be also positive.
A strategic reorganization of the use of time and space in the dining room that
would reduce the feeling of discomfort and noise could contribute to a better and
more enjoyable use of it, while contributing to a better perception of food and
welfare in general.
PMID- 25137282
TI - Anthropometric, food intake differences and applicability of low-cost instruments
for the measurement of body composition in two distinct groups of individuals
with short bowel syndrome.
AB - INTRODUCTION: Short bowel syndrome is associated with weight loss due to
nutrient, electrolyte and fluid malabsorption. In view of the pathophysiology of
SBS, all patients would be expected to exhibit similar clinical signs and
symptoms, whereas many variations occur probably due to the adaptive capacity of
the remaining small intestine in order to compensate for the resected area.
OBJECTIVE: To determine whether there is a difference in nutritional status and
food intake between patients receiving PNT, patients who do not receive PNT but
are monitored on an ambulatory basis, and control subjects, and 2) to determine
body composition by two different methods, i.e., electrical bioimpedance and skin
fold measurement. METHODS: This was a case-control study where the subjects were
divided into three groups: parenteral group (PG) - adults with a history of SBS
intermittently using PNT; ambulatory group (AG) - adults with a history of SBS
who do not receive PNT; control group (CG) - adults with no history of intestinal
resections and/or use of PNT. The volunteers were submitted to measurements of
body weight, height, body composition by bioimpedance analysis and assessment of
food intake using a food frequency questionnaire. Univariate analysis of variance
(ANOVA) with the aid of the SAS(r) 9.2. software, using the PROC GLM feature. The
Student t-test was used to compare the instruments for the assessment of body
composition, with the aid of the PROC TTEST feature of the SAS(r) 9.2 software.
RESULTS: Thirty-two volunteers, 19 women and 13 men, participated in the study.
The PNT group consisted of 9 volunteers, 4 women and 5 men, with a mean (+/- SD)
age of 57 +/- 9 years. The nutrition status and food intake were different
between the groups. There was no difference in percent body fat measured by
anthropometry and bioimpedance analysis. DISCUSSION AND CONCLUSION: Large
resections, as well as the resected portions, explain the greater nutritional
impairment of PG compared to AG and CG, although no significant difference in
food consumption was detected between these three groups. Since the use of PNT
can lead to a state of hyperhydration, the results of BIA should be interpreted
with caution, in view of the fact that the lean mass determined by this method
varies positively with the hydration state of an individual.
PMID- 25137284
TI - Development of type 2 diabetes mellitus thirty-one years after Billroth II in a
patient asking for diabetes surgery.
AB - INTRODUCTION: Diabetes surgery in obese and slim patients seems to be a superior
alternative to the current medical treatment. Gastric bypass is an alternative
treatment for diabetes. Nevertheless, there are still doubts whether diabetes can
recur if you gain weight or if the effects are maintained over time. Other
questions refer to the type of surgery to make the bypass limb length or
reservoir size for the resolution of the Diabetes Mellitus. PRESENTATION OF CASE:
Male patient 69-year-old came to us in order to perform tailored One Anastomosis
Gastric Bypass (BAGUA) to treat his type 2 diabetes mellitus and metabolic
syndrome. He has a history of peptic ulcer treated with subtotal gastrectomy and
Billroth II reconstruction 49 years ago. He currently is not obese and developed
diabetes 31 years after surgery. DISCUSSION: Globally there are no reports of
patients with normal BMI that after performing gastric bypass developed diabetes
mellitus. There are cases where obese diabetic patients after gastric bypass
improve or remits the T2DM, but it relapses due to insufficient weight loss or
gain it. The patient with gastric bypass Billroth II type, should not developed
diabetes. He is normal weight and not had weight gain that could be linked to the
development of diabetes. CONCLUSIONS: The results generated by bariatric surgery
are encouraging, but still do not clarify the precise way how surgery produces
rapid improvement of systemic metabolism as in diabetes, but in our patient, the
effect was quite different because the gastric bypass had no protective effect
against diabetes.
PMID- 25137289
TI - The role of cervical and ocular vestibular evoked myogenic potentials in the
assessment of patients with vestibular schwannomas.
AB - OBJECTIVES: To investigate the clinical utility of VEMPs in patients suffering
from unilateral vestibular schwannoma (VS) and to determine the optimal
stimulation parameter (air conducted sound, bone conducted vibration) for
evaluating the function of the vestibular nerve. METHODS: Data were obtained in
63 patients with non-operated VS, and 20 patients operated on VS. Vestibular
function was assessed by caloric, cervical and ocular VEMP testing. 37/63
patients with conclusive ACS ocular VEMPs responses were studied separately.
RESULTS: In the 63 non-operated VS patients, cVEMPs were abnormal in 65.1% of
patients in response to AC STB and in 49.2% of patients to AC clicks. In the
37/63 patients with positive responses from the unaffected side, oVEMPs were
abnormal in 75.7% of patients with ACS, in 67.6% with AFz and in 56.8% with
mastoid BCV stimulation. In 16% of the patients, VEMPs were the only abnormal
test (normal caloric and normal hearing). Among the 26 patients who did not show
oVEMP responses on either side with ACS, oVEMPs responses could be obtained with
AFz (50%) and with mastoid stimulation (89%). CONCLUSIONS: The VEMP test
demonstrated significant clinical value as it yielded the only abnormal test
results in some patients suffering from a unilateral vestibular schwannoma. For
oVEMPs, we suggest that ACS stimulation should be the initial test. In patients
who responded to ACS and who had normal responses, BCV was not required. In
patients with abnormal responses on the affected side using ACS, BCV at AFz
should be used to confirm abnormal function of the superior vestibular nerve. In
patients who exhibited no responses on either side to ACS, BCV was the only
approach allowing assessment of the function of the superior vestibular nerve. We
favor using AFz stimulation first because it is easier to perform in clinical
practice than mastoid stimulation.
PMID- 25137290
TI - A multimeric MR-optical contrast agent for multimodal imaging.
AB - We describe the design, synthesis and in vitro evaluation of a multimodal and
multimeric contrast agent. The agent consists of three macrocyclic Gd(III)
chelates conjugated to a fluorophore and possesses high relaxivity, water
solubility, and is nontoxic. The modular synthesis is amenable for the
incorporation of a variety of fluorophores to generate molecular constructs for a
number of applications.
PMID- 25137291
TI - A cotton (Gossypium hirsutum) gene encoding a NAC transcription factor is
involved in negative regulation of plant xylem development.
AB - NAC proteins that compose of one large family of plant specific transcription
factors (TF) play the important roles in many biological processes (such as
morphogenesis, development, senescence and stress signal transduction). In this
study, a gene (designated as GhXND1) encoding a NAC transcription factor was
identified in cotton. Sequence analysis indicated that GhXND1 gene contains two
introns inserted in its open reading frame (ORF). GhXND1 protein is localized in
the cell nucleus, and displays the transactivation activity. GhXND1 transcripts
were mainly detected in cotyledons, petals, roots, hypocotyls and stems, but
little or no signals of GhXND1 expression were found in the other tissues.
Ectopic expression of GhXND1 in Arabidopsis resulted in a reduction in number of
xylem vessel cells and cell wall thickness of interfascicular fibers in the
transgenic plants, compared with those of wild type. And expression of some cell
wall biosynthesis-related genes was down-regulated in the GhXND1 transgenic
plants. Collectively, the data presented in this study suggested that GhXND1 may
be involved in regulation of plant xylem development.
PMID- 25137292
TI - Molecular characterization and expression analysis of the critical floral genes
in hickory (Carya cathayensis Sarg.).
AB - The full ORFs of three floral genes in hickory (Carya cathayensis Sarg.), CcAGL24
(the AGAMOUS-LIKE24 homolog), CcSOC1 (the SUPPRESSOR OF OVEREXPRESSION OF
CONSTANS1 homolog) and CcAP1 (the APETALA1 homolog) are derived using a 5' RACE
PCR protocol. Through sequence alignment and phylogenetic analysis, it is
demonstrated that the three genes belong to the MADS-Box family. According to the
evolutionary trees of the three genes, the homologous genes from the same family
cluster well together, while those from different orders doesn't match
evolutionary regularity of individual organisms. The result of Quantitative RT
PCR analysis shows that the transcriptional levels of the three genes are up
regulated in early stage and down-regulated in late stage in pistillate floral
development. However, it takes different time to reach respective expression peak
among the three genes. In staminate floral development, the transcription trend
of the three genes is up-regulated, subsequently down-regulated, and then up
regulated again. Nevertheless, those trajectories, peaks, expression levels,
inflection points are different in pistillate floral development. The result
suggests that their functions are different in between pistillate and staminate
floral development. The probable ordinal site of the three genes in the flowering
network from top down is CcAGL24, CcSOC1, and CcAP1, which is identical to that
in herbaceous plants. Moreover, several adverse environmental factors trigger
several negative genes and then confine the development of staminate floral buds.
Our results suggest the possible relationship among the three critical floral
genes and their functions throughout the floral development in hickory.
PMID- 25137294
TI - Nano-titanium dioxide bioreactivity with human alveolar type-I-like epithelial
cells: Investigating crystalline phase as a critical determinant.
AB - There can be significant variability between bioreactivity studies of
nanomaterials that are apparently the same, possibly reflecting differences in
the models used and differing sources of experimental material. In this study, we
have generated two crystal forms of titanium dioxide nanoparticles (nano-TiO2),
pure anatase and pure rutile to address the hypothesis that the bioreactivity of
these nanoparticles with human alveolar epithelium will depend on their crystal
phase. We used a human alveolar type-I-like epithelial cell model (TT1; generated
in-house from primary human alveolar epithelial type II cells); these cells cover
95% of the alveolar epithelial surface area and are an important target cell for
inhaled nanomaterials. Using literature as a guide, we hypothesised that pure
anatase nano-TiO2 would display greater bioreactivity with TT1 cells in
comparison to pure rutile nano-TiO2. However, we found the profile and pattern of
inflammatory mediator release was similar between these two nano-TiO2 formats,
although pure rutile treatment caused a small, but consistently greater, response
for IL-6, IL-8 and MCP-1. Interestingly, the temporal induction of oxidative
stress (increased reactive oxygen species levels and depleted glutathione) varied
markedly between the different nano-TiO2 formats. We have shown that a
combination of using nanomaterials synthesised specifically for toxicological
study and the use of a highly relevant, reproducible human lung cell model,
offers a useful approach to delineating the physicochemical properties of
nanomaterials that may be important in their cellular reactivity.
PMID- 25137293
TI - Activation-induced cell death drives profound lung CD4(+) T-cell depletion in HIV
associated chronic obstructive pulmonary disease.
AB - RATIONALE: As overall survival improves, individuals with HIV infection become
susceptible to other chronic diseases, including accelerated chronic obstructive
pulmonary disease (COPD). OBJECTIVES: To determine whether individuals with HIV
associated COPD exhibit dysregulated lung mucosal T-cell immunity compared with
control subjects. METHODS: Using flow cytometry, we evaluated peripheral blood
and lung mucosal T-cell immunity in 14 HIV(+)COPD(+), 13 HIV(+)COPD(-), and 7
HIV(-)COPD(+) individuals. MEASUREMENTS AND MAIN RESULTS: HIV(+)COPD(+)
individuals demonstrated profound CD4(+) T-cell depletion with reduced CD4/CD8 T
cell ratios in bronchoalveolar lavage-derived lung mononuclear cells, not
observed in peripheral blood mononuclear cells, and diminished CD4(+) T cell
absolute numbers, compared with control subjects. Furthermore, HIV(+)COPD(+)
individuals demonstrated decreased pulmonary HIV-specific and staphylococcal
enterotoxin B-reactive CD4(+) memory responses, including loss of
multifunctionality, compared with HIV(+)COPD(-) control subjects. In contrast,
lung mucosal HIV-specific CD8(+) T-cell responses were preserved. Lung CD4(+) T
cells from HIV(+)COPD(+) individuals expressed increased surface Fas death
receptor (CD95) and programmed death-1, but similar bronchoalveolar lavage viral
loads as control subjects. However, programmed death-1 expression inversely
correlated with HIV-specific lung CD4(+)IFN-gamma(+) T-cell responses, suggesting
functional exhaustion. Moreover, lung CD4(+) T cells from HIV(+)COPD(+) patients
demonstrated increased basal and HIV antigen-induced expression of the early
apoptosis marker annexin V compared with control subjects, which was
significantly attenuated with anti-Fas blockade. Lastly, lung mucosal, but not
blood, CD4(+)/CD8(+) ratios from HIV(+) patients significantly correlated with
the FEV1, but not in HIV(-)COPD(+) patients. CONCLUSIONS: Together, our results
provide evidence for profound lung mucosal CD4(+) T-cell depletion via a Fas
dependent activation-induced cell death mechanism, along with impaired HIV
specific CD4(+) immunity as immunologic features of HIV-associated COPD.
PMID- 25137295
TI - Inhibition of potential uptake pathways for silver nanoparticles in the estuarine
snail Peringia ulvae.
AB - Mechanisms involved in the uptake of Ag NPs, and NPs in general, have been long
debated within nano-ecotoxicology. In vitro studies provide evidence of the
different available uptake pathways, but in vivo demonstrations are lacking. In
this study, pharmacological inhibitors were employed to block specific uptake
pathways that have been implicated in the transport of metal NPs and aqueous
metal forms; phenamil (inhibits Na(+) channel), bafilomycin A1 (H(+) proton
pump), amantadine (clathrin-mediated endocytosis), nystatin (caveolae-mediated
endocytosis) and phenylarsine oxide (PAO, macropinocytosis). Peringia ulvae
(snails) were exposed to 150 ug Ag L(-1) added as citrate capped Ag NPs or
aqueous Ag (AgNO3) in combination with inhibitor treatment (determined by
preliminary studies). Reductions in accumulated tissue burdens caused by the
inhibitors were compared to control exposures (i.e. no inhibition) after 6 and 24
h. No inhibitor treatment completely eliminated the uptake of Ag in either
aqueous or NP form, but all inhibitor treatments, except phenamil, significantly
reduced the uptake of Ag presented as Ag NPs. Clathrin- and caveolae-mediated
endocytosis appear to be mechanisms exploited by Ag NPs, with the latter pathway
only active at 24 h. Inhibition of the H(+) proton pump showed that a portion of
Ag NP uptake is achieved as aqueous Ag and is explained by the dissolution of the
particles (~25% in 24 h). This in vivo study demonstrates that uptake of Ag from
Ag NPs is achieved by multiple pathways and that these pathways are
simultaneously active.
PMID- 25137296
TI - Assessing orally bioavailable commercial silver nanoparticle product on human
cytochrome P450 enzyme activity.
AB - Nanotechnology produces a wide range of medicinal compounds, including
nanoparticulate silver, which are increasingly introduced in various forms for
consumer use. As with all medicinal compounds, potential drug interactions are an
important consideration for ingested silver nanoparticles. Nanoparticulate silver
drug interactions may be mediated through induced oxidative stress in liver
tissue where the majority of systemically bioavailable silver nanoparticles is
found. To investigate whether an orally ingested commercially available colloidal
silver nanoproduct produces pharmacokinetic interference on select cytochrome
P450 enzymes, a prospective, single-blind, controlled in vivo human study using
simultaneous administration of standardized probes for P450 enzyme classes
CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 was conducted. Oral ingestion of a
commercial colloidal silver nanoproduct produces detectable silver in human serum
after 14 days of dosing. This silver, however, elicits no demonstrable clinically
significant changes in metabolic, hematologic, urinary, physical findings or
cytochrome P450 enzyme inhibition or induction activity. Given their increasingly
broad, diverse human exposures, future characterization of human cytochrome P450
enzyme activity for other systemically bioavailable nanotechnology products are
warranted.
PMID- 25137297
TI - Use of ultrasound for lower extremity.
AB - PURPOSE OF REVIEW: To explore the recent advances in the use of ultrasound for
lower extremity blocks, including approaches to the lumbar and sacral plexus
blocks. RECENT FINDINGS: Procedures of the lower extremity often require blocks
of the lumbar and sacral plexuses. The use of ultrasound offers some advantages,
including the possibility to directly visualize the distribution of local
anesthetics. SUMMARY: Lower extremity blocks under ultrasound guidance often
require advanced skills because of the depth of target nerves. This review
summarizes the recent advances in the use of ultrasound guidance over traditional
techniques.
PMID- 25137298
TI - How to give a scientific talk, present a poster, and write a research paper or
proposal.
PMID- 25137299
TI - Improved early performance of turkey poults given an Aloe ferox leaf extract with
bentonite.
AB - AT-402 (20 g/kg), a proprietary blend of Aloe ferox leaf extract and calcium
bentonite, had no adverse effect on poult body weights at 3 weeks of age. Lower
body weights and lower feed consumption were observed in 4-week-old poults given
10 and 20 g/kg of AT-402 compared to poults given 0 or 5 g/kg. Floor-reared
poults, given either 5 or 10 g/kg AT-402 to 4 weeks of age, were significantly
heavier than controls (0 g/kg AT-402), and feed conversion ratios for AT-402
given poults were improved. Xylose uptake in 5 g/kg AT-402-fed poults was
significantly greater than in poults given AT-402 at 0 and 10 g/kg, reflecting
increased body weights of 5 g/kg AT-402-fed poults. Delayed access by poults to
the AT-402 until 10 d of age also improved 4-week body weights, suggesting that
the AT-402 might improve performance as soon as it is given. AT-402 at 5 g/kg was
most efficacious as demonstrated by improved body weights and feed conversions.
PMID- 25137301
TI - Nitrogen self-doped porous carbon from surplus sludge as metal-free
electrocatalysts for oxygen reduction reactions.
AB - Nitrogen self-doped porous carbon was prepared by calcination treatment of
surplus sludge, a toxic byproduct from microbial wastewater treatments, and
exhibited a mesoporous structure, as manifested in scanning and transmission
electron microscopic measurements. Nitrogen adsorption/desorption studies showed
that the porous carbon featured a BET surface area as high as 310.8 m(2)/g and a
rather broad range of pore size from 5 to 80 nm. X-ray photoelectron
spectroscopic studies confirmed the incorporation of nitrogen into the graphitic
matrix forming pyridinic and pyrrolic moieties. Interestingly, the obtained
porous carbon exhibited apparent electrocatalytic activity in oxygen reduction in
alkaline media, with the optimal temperatures identified within the range of 600
to 800 degrees C, where the number of electron transfers involved in oxygen
reduction was estimated to be 3.5 to 3.7 and the performance was rather
comparable to leading literature results as a consequence of deliberate
engineering of the graphitic matrix by nitrogen doping.
PMID- 25137300
TI - Bariatric surgery improves the cavernosal neuronal, vasorelaxation, and
contraction mechanisms for erectile dysfunction as result of amelioration of
glucose homeostasis in a diabetic rat model.
AB - BACKGROUND: Bariatric surgery is an effective treatment option for both obesity
and obesity-related type 2 diabetes mellitus (T2DM). However, little is known
regarding the effects of bariatric surgery on erectile dysfunction among patients
with T2DM. Therefore, we investigated whether bariatric surgery would lead to
structural and biochemical changes in the corpus cavernosum. MATERIAL AND METHOD:
Twenty-five male Otsuka Long-Evans Tokushima Fatty rats were assigned to either a
control group (sham operation, n = 10) or a bariatric surgery group (gastric
bypass surgery, n = 15). Four weeks after the operation, each group of rats was
evaluated with an oral glucose tolerance test (OGTT). The penile intracavernous
pressure was measured for erectile functional analysis. Histologic evaluation of
the tissue was performed with Masson's trichrome staining. Endothelial nitric
oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), Rho kinase, and 8
hydroxy-2-deoxyguanosine (8-OHdG) levels in the corpus cavernosum were assayed by
using western blot and ELISA. RESULTS: The mean body weight of the bariatric
surgery group was lower than the control group (p = 0.002). The postoperative
OGTT result was lower in the bariatric surgery group than in the control group (p
= 0.014), and this was lower than the preoperative value (p = 0.037). The
intracavernous pressure/mean arterial pressure ratio was higher in the bariatric
surgery group compared to the control group (p = 0.021), and a higher cavernosum
smooth muscle/collagen ratio was observed in the bariatric surgery group compared
to the control group (p = 0.025). Likewise, the expression of eNOS and nNOS was
higher in bariatric surgery group than in the control group (p = 0.027 and p =
0.008, respectively). Decreased expression of Rho kinase and levels of 8-OHdG
were observed in the bariatric surgery group (p = 0.032). CONCLUSION: In this
animal model, bariatric surgery appears to ameliorate T2DM-related metabolic
dysfunction leading to structural and biochemical changes in the corpus
cavernosum, and thus, results in improvement of erectile dysfunction associated
with T2DM.
PMID- 25137302
TI - Measuring bacterial adaptation dynamics at the single-cell level using a
microfluidic chemostat and time-lapse fluorescence microscopy.
AB - We monitored the dynamics of cell dimensions and reporter GFP expression in
individual E. coli cells growing in a microfluidic chemostat using time-lapse
fluorescence microscopy. This combination of techniques allows us to study the
dynamical responses of single bacterial cells to nutritional shift-down or shift
up for longer times and with more precision over the chemical environment than
similar experiments performed on conventional agar pads. We observed two E. coli
strains containing different promoter-reporter gene constructs and measured how
both their cell dimensions and the GFP expression change after nutritional
upshift and downshift. As expected, both strains have similar adaptation dynamics
for cell size rearrangement. However, the strain with a ribosomal RNA promoter
dependent reporter has a faster GFP production rate than the strain with a
constitutive promoter reporter. As a result, the mean GFP concentration in the
former strain changes rapidly with the nutritional shift, while that in the
latter strain remains relatively stable. These findings characterize the present
microfluidic chemostat as a versatile platform for measuring single-cell
bacterial dynamics and physiological transitions.
PMID- 25137305
TI - [Individualised parent counselling in paediatric practices for the reduction of
second-hand smoke exposure of their children: a feasibility study].
AB - AIM: The aim of this study was to test the feasibility of a web-based programme
provided by paediatric practices for counselling parents to reduce second-hand
smoke exposure of their children. METHODS: Accompanying persons of children were
systematically screened concerning tobacco smoking at their home in 2 Swiss
paediatric practices. They were invited for programme participation if they or
their partners smoked at home regularly. The web-based programme provided at
least 1 computer-tailored counselling letter. Upto 3 additional counselling
letters could be requested online by the participants over a period of 3 months.
The letters were tailored according to the indoor smoking behaviour of the
parents and considered individual barriers and resources for the establishment of
a smoke-free home. Additionally, further information and advice could be
requested on the programme website. Feasibility indicators were the participation
rate, programme use, and programme evaluation by the participants. RESULTS: 3 055
(82.3%) of 3 712 accompanying persons of children in the paediatric practices
were screened concerning tobacco smoking at their home. 96 (56.8%) of 169
eligible persons participated in the programme. 68 (70.8%) of the 96 programme
participants could be reassessed at post assessment. 9 (15.0%) of 60 participants
who provided a valid e-mail address requested more than one counselling letter.
The counselling letters and the web-based programme were evaluated positively by
the programme participants. CONCLUSION: Systematic screening combined with the
provision of individually tailored counselling letters for parents to reduce
second-hand smoke exposure of their children was feasible in paediatric
practices. Possible strategies to in-crease the use and reach of the programme
are -discussed.
PMID- 25137306
TI - [Ambulatory care-sensitive conditions in Germany: a small area analysis (2006
2009)].
AB - PURPOSE: The paper aims (1) to identify and depict cartographically ambulatory
care-sensitive conditions in Germany (based on data for the years 2006-2009) and
(2) to discuss the implications. METHOD: The selection of ambulatory care
sensitive conditions (ACSC) was based on a literature review by Purdy et al.
(2009) because a German catalogue of ACSC does not yet exist. Five of these
indications were excluded due to limited data -access or a low number of cases.
Additionally, 2 -diagnoses that are potentially relevant for Germany were
included. Subsequently, diagnosis-specific hospitalisation rates were calculated
for each of the 412 counties (Stadtkreise and Landkreise). The spatial
distribution of 6 selected diag-noses (heart failure, diabetes, dehydration and
gastroenteritis, ENT infections, influenza and pneumonia as well as
schizophrenia) was depicted and discussed. Furthermore, an overall analysis of
diagnoses analysis was performed. RESULTS: Based on the overall analysis,
counties with high hospitalisation rates were identified in Mecklenburg-Western
Pomerania, Saxony-Anhalt and Thuringia as well as to a lesser degree in
Brandenburg, Saarland, Rhineland Palatinate and North Rhine-Westphalia (for men
and women). Low hospitalisation rates were often present in counties in Baden
Wuerttemberg. Based on the diagnosis-specific analysis, some regional clusters
could be identified. Thus, high hospitalisa-tion rates for heart failure,
diabetes, ENT infections were especially present in Eastern Germany. In contrast,
there were no distribution patterns for high hospitalisation rates due to
influenza and pneumonia. However, differences could be also identified between
rural and urban regions: while hospitalisations due to dehydration and
gastroenteritis were more often in rural -districts, hospitalisations due to
schizophrenia occurred more frequently in urban regions. CONCLUSION: Knowledge of
the spatial distribution of ACSC -rates serves as an important indicator for the
identification of districts where health-care quality and access (structural-
related) can be optimised. The analysis of hospitalisation rates for 6 selected
indications showed that for some indications there were clear regional
differences in the distribution of ACSCs in -Germany.
PMID- 25137307
TI - [Specialised out-patient palliative care (SAPV) in Bavaria: efficiency,
structural and process-related effects and rural care].
AB - Empirical indications show that specialised out-patient palliative care (SAPV),
introduced in Germany in 2007, allows critically ill and dying patients to pass
away within their own home even under complex symptoms. SAPV avoids emergency and
hospital interferences, and the patient's wish to stay at home until the very end
can be respected in most cases. The performance of SAPV is not solely focused on
medical and patient-care aspects. It includes consulting and coordination work
and also psycho-social support both of patients and family members. Within this
framework, different active factors could be identified that are essential for
high-quality care. Furthermore, the results show that the general ambulant care
commodities on site determine the need, the extent and even the efficiency of
SAPV. At the same time, SAPV changes also the respective care environment: it
changes the roles of previous care providers and offers new resources, though not
all existing resources (e. g., hospice services) are taken into account.
PMID- 25137304
TI - Serum nutritional biomarkers and their associations with sleep among US adults in
recent national surveys.
AB - BACKGROUND: The associations between nutritional biomarkers and measures of sleep
quantity and quality remain unclear. METHODS: Cross-sectional data from the
National Health and Nutrition Examination Surveys (NHANES) 2005-2006 were used.
We selected 2,459 adults aged 20-85, with complete data on key variables. Five
sleep measures were constructed as primary outcomes: (A) Sleep duration; (B)
Sleep disorder; (C) Three factors obtained from factor analysis of 15 items and
labeled as "Poor sleep-related daytime dysfunction" (Factor 1), "Sleepiness"
(Factor 2) and "Sleep disturbance" (Factor 3). Main exposures were serum
concentrations of key nutrients, namely retinol, retinyl esters, carotenoids
(alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein+zeaxanthin, lycopene),
folate, vitamin B-12, total homocysteine (tHcy), vitamin C, 25-hydroxyvitamin D
(25(OH)D) and vitamin E. Main analyses consisted of multiple linear, logistic and
multinomial logit models. RESULTS: Among key findings, independent inverse
associations were found between serum vitamin B-12 and sleep duration, 25(OH)D
and sleepiness (as well as insomnia), and between folate and sleep disturbance.
Serum total carotenoids concentration was linked to higher odds of short sleep
duration (i.e. 5-6 h per night) compared to normal sleep duration (7-8 h per
night). CONCLUSIONS: A few of the selected serum nutritional biomarkers were
associated with sleep quantity and quality. Longitudinal studies are needed to
ascertain temporality and assess putative causal relationships.
PMID- 25137308
TI - [Assistive Services in the Workplace of People with Hearing Impairment in the
State of North Rhine-Westphalia].
AB - AIM OF THE STUDY: Assistive services in the workplace are an important aspect of
the participation of people with hearing impairment in working life. This article
presents the results of the GINKO study and an survey conducted by the University
of Cologne on behalf of the MAIS in order to provide a comprehensive examination
of the employment situation of hearing impaired people in North Rhine-Westphalia.
The GINKO study examines the impact of laws on the integration of hard-of-hearing
and deaf people as well as people who have become deaf as adults, focusing on
communication and organizations; this project was funded by the German Federal
Ministry for Labour and Social Affairs (BMAS). METHOD: In the GINKO study,
conducted in cooperation with the German Association of the Hard of Hearing and
the German Association of the Deaf, a standardised questionnaire with questions
about the workplace was administered to employed people with hearing impairments.
The questionnaire was administered on paper and was also available online
accompanied by sign language videos. The University of Cologne study in North
Rhine-Westphalia examined the service situation of hard-of-hearing, deaf and deaf
blind people through face-to-face interviews and government statistics. RESULTS:
The results of the nationwide GINKO study show that hearing-impaired people in
North Rhine-Westphalia draw on assistive services in employment more often than
hearing-impaired people in the rest of Germany. The study found statistically
significant differences in the categories of "maintenance and development of
professional knowledge and skills" and "psychosocial support in conflict
situations resulting from disability". CONCLUSION: One reason for the more
positive evaluations of the participants in North Rhine-Westphalia as compared to
other regions in Germany could be the particular network of support services in
that state. However, the overall positive results from North Rhine-Westphalia
should not obscure the fact that a majority of participants in many areas of
North Rhine-Westphalia reported much less positive evaluations. They reported
that they did not (yet) have an accessible workplace and that assistive services
are not available to all hearing impaired workers.
PMID- 25137309
TI - Association of NCAM1 polymorphisms with autism and parental age at conception in
a Chinese Han population.
AB - AIMS: The neural cell adhesion molecule (NCAM) has been reported to be involved
in the development of the central nervous system and its mRNA level might
decrease in the serum of autistic patients. However, there was no evidence of the
association of the NCAM1 gene polymorphisms with autism. In the present study, we
enrolled 237 children with autism and 451 healthy control subjects. Then, we used
the direct DNA sequencing for genotyping five tag single-nucleotide polymorphisms
(SNPs) in the NCAM1 gene. RESULTS: By using case-control association analyses, we
found that three SNPs at the NCAM1 gene were associated with autism (rs 4937786,
p=0.015; rs 12418058, p=0.0076; rs 1436109, p=0.0023). Two of them remained
significant after the Bonferroni multiple testing correction (rs 12418058,
P(corrected) =0.038; rs 1436109, P(corrected) =0.012). Moreover, two of the SNPs
were associated with the parental age at conception in autism (rs 12418058,
p=0.037; rs 1436109, p=0.01). CONCLUSION: These results showed that NCAM1 might
play an important role in the pathogenesis of autism.
PMID- 25137310
TI - Enantioselective olefin metathesis with cyclometalated ruthenium complexes.
AB - The success of enantioselective olefin metathesis relies on the design of
enantioenriched alkylidene complexes capable of transferring stereochemical
information from the catalyst structure to the reactants. Cyclometalation of the
NHC ligand has proven to be a successful strategy to incorporate stereogenic
atoms into the catalyst structure. Enantioenriched complexes incorporating this
design element catalyze highly Z- and enantioselective asymmetric ring
opening/cross metathesis (AROCM) of norbornenes and cyclobutenes, and the
difference in ring strain between these two substrates leads to different
propagating species in the catalytic cycle. Asymmetric ring closing metathesis
(ARCM) of a challenging class of prochiral trienes has also been achieved. The
extent of reversibility and effect of reaction setup was also explored. Finally,
promising levels of enantioselectivity in an unprecedented Z-selective asymmetric
cross metathesis (ACM) of a prochiral 1,4-diene was demonstrated.
PMID- 25137311
TI - Trait-specific responses of wild bee communities to landscape composition,
configuration and local factors.
AB - Land-use intensification and loss of semi-natural habitats have induced a severe
decline of bee diversity in agricultural landscapes. Semi-natural habitats like
calcareous grasslands are among the most important bee habitats in central
Europe, but they are threatened by decreasing habitat area and quality, and by
homogenization of the surrounding landscape affecting both landscape composition
and configuration. In this study we tested the importance of habitat area,
quality and connectivity as well as landscape composition and configuration on
wild bees in calcareous grasslands. We made detailed trait-specific analyses as
bees with different traits might differ in their response to the tested factors.
Species richness and abundance of wild bees were surveyed on 23 calcareous
grassland patches in Southern Germany with independent gradients in local and
landscape factors. Total wild bee richness was positively affected by complex
landscape configuration, large habitat area and high habitat quality (i.e. steep
slopes). Cuckoo bee richness was positively affected by complex landscape
configuration and large habitat area whereas habitat specialists were only
affected by the local factors habitat area and habitat quality. Small social
generalists were positively influenced by habitat area whereas large social
generalists (bumblebees) were positively affected by landscape composition (high
percentage of semi-natural habitats). Our results emphasize a strong dependence
of habitat specialists on local habitat characteristics, whereas cuckoo bees and
bumblebees are more likely affected by the surrounding landscape. We conclude
that a combination of large high-quality patches and heterogeneous landscapes
maintains high bee species richness and communities with diverse trait
composition. Such diverse communities might stabilize pollination services
provided to crops and wild plants on local and landscape scales.
PMID- 25137312
TI - An abnormal N-heterocyclic carbene-carbon dioxide adduct from imidazolium acetate
ionic liquids: the importance of basicity.
AB - In the reaction of 1-ethyl-3-methylimidazolium acetate [C2C1Im][OAc] ionic liquid
with carbon dioxide at 125 degrees C and 10 MPa, not only the known N
heterocyclic carbene (NHC)-CO2 adduct I, but also isomeric aNHC-CO2 adducts II
and III were obtained. The abnormal NHC-CO2 adducts are stabilized by the
presence of the polarizing basic acetate anion, according to static DFT
calculations and ab initio molecular dynamics studies. A further possible
reaction pathway is facilitated by the high basicity of the system, deprotonating
the initially formed NHC-CO2 adduct I, which can then be converted in the
presence of the excess of CO2 to the more stable 2-deprotonated anionic abnormal
NHC-CO2 adduct via the anionic imidazolium-2,4-dicarboxylate according to DFT
calculations on model compounds. This suggests a generalizable pathway to
abnormal NHC complex formation.
PMID- 25137313
TI - Microextraction by packed sorbent liquid chromatography with time-of-flight mass
spectrometry of triazines employing a molecularly imprinted polymer.
AB - Molecularly imprinted polymers for the determination of triazines were
synthesized by precipitation using atrazine as template, methacrylic acid as
functional monomer, ethylene glycol dimethacrylate as crosslinker, and 2,2'
azobisisobutrynitrile as initiator. The polymers were characterized by infrared
spectroscopy and scanning electron microscopy and packed in a device for
microextraction by packed sorbent aiming for the preconcentration/cleanup of
herbicides, such as atrazine, simazine, simetryn, ametryn, and terbutryn in corn
samples. Liquid chromatography coupled with time-of-flight mass spectrometry was
used for the separation and determination of the herbicides. The selectivity
coefficient of molecularly imprinted polymers was compared with that of
nonimprinted polymer for the binary mixtures of atrazine/propanil and
atrazine/picloram, and the values obtained were 15.6 and 2.96, respectively. The
analytical curve ranged from 10 to 80 MUg/kg (r = 0.989) and the limits of
detection and quantification in the corn matrices were 3.3 and 10 MUg/kg,
respectively. Intra- and interday precisions were < 14.8% and accuracy was better
than 90.9% for all herbicides. Polymer synthesis was successfully applied to the
cleanup and preconcentration of triazines from fortified corn samples with 91.1
109.1% of recovery.
PMID- 25137316
TI - [Procalcitonin as a marker of the postoperative infection in cardiovascular
surgery].
AB - BACKGROUND: Procalcitonin( PCT) is a new diagnostic marker of severe bacterial
infection and sepsis. PURPOSE: To evaluate the usefulness of PCT in patients with
suspicion of bacterial infection after cardiovascular surgery. METHODS: From
January 2012 to December 2012, 150 consecutive patients after cardiovascular
surgery were studied retrospectively. Postoperative infection was diagnosed under
Centers for Disease Control and Prevention (CDC) guideline for healthcare
associated infection, and biomarker levels and microbiological specimen were
evaluated. RESULTS: Only blood stream infection group revealed higher PCT levels(
median 5.0 ng/ml) than non blood stream infection group( median 0.1
ng/ml)[p<0.01]. CONCLUSION: PCT is the best biomarker available for the clinical
diagnosis of blood stream infection after cardiovascular surgery.
PMID- 25137318
TI - [Determinants of prolonged mechanical ventilation after cardiac surgery].
AB - PURPOSE: This study aimed to examine factors that delay weaning from ventilation
after cardiac surgery. METHODS: A retrospective examination was made on 1,033
patients who had undergone cardiac surgery through a midsternal incision between
January 2009 and July 2011. The items examined were duration of postoperative
ventilation, patient's background, and other surgical information. If patients
were weaned within 24 hours from intensive care unit (ICU) admission, they were
included in the timely weaning group. If patients required 24 hours or more to be
weaned, they were included in the delayed weaning group. RESULTS: There was a
relationship between prolonged ventilation and the following factors: emergency
surgery, history of arrhythmia, history of motor system disorder, preoperative
estimated glomerular filtration rate (eGFR), preoperative New York Heart
Association (NYHA) classification, preoperative left ventricular ejection
fraction (LVEF), operative method, operative time, blood loss, intraoperative
fluid management, and number of days from surgery until achievement of
independent gait. The independent factors delaying extubation were emergency
surgery, preoperative NYHA classification, preoperative LVEF, operative method,
operative time, blood loss, and intraoperative fluid management(p<0.05).
CONCLUSION: Surgical invasiveness and preoperative heart failure were involved in
the prolonged ventilation after cardiac surgery.
PMID- 25137314
TI - Increased microstructural white matter correlations in left, but not right,
temporal lobe epilepsy.
AB - Microstructural white matter tract correlations have been shown to reflect known
patterns of phylogenetic development and functional specialization in healthy
subjects. The aim of this study was to establish intertract correlations in a
group of controls and to examine potential deviations from normality in temporal
lobe epilepsy (TLE). We investigated intertract correlations in 28 healthy
controls, 21 left TLE (LTLE) and 23 right TLE (RTLE). Nine tracts were
investigated, comprising the parahippocampal fasciculi, the uncinate fasciculi,
the arcuate fasciculi, the frontoparietal tracts, and the fornix. An abnormal
increase in tract correlations was observed in LTLE, while RTLE showed intertract
correlations similar to controls. In the control group, tract correlations
increased with increasing fractional anisotropy (FA), while in the TLE groups
tract correlations increased with decreasing FA. Cluster analyses revealed
agglomeration of bilateral pairs of homologous tracts in healthy subjects, with
such pairs separated in our LTLE and RTLE groups. Discriminant analyses aimed at
distinguishing LTLE from RTLE, revealing that tract correlations produce higher
rates of accurate group classification than FA values. Our results confirm and
extend previous work by showing that LTLE compared to RTLE patients display not
only more extensive losses in microstructural orientation but also more aberrant
intertract correlations. Aberrant correlations may be related to pathologic
processes (i.e., seizure spread) or to adaptive processes aimed at preserving key
cognitive functions. Our data suggest that tract correlations may have predictive
value in distinguishing LTLE from RTLE, potentially moving diffusion imaging to a
place of greater prominence in clinical practice.
PMID- 25137319
TI - [Intravascular papillary endothelial hyperplasia of the lung].
AB - We report a rare case of pulmonary intravascular papillary endothelial
hyperplasia. The patient was a 63-year-old male. Multiple lung nodules were noted
on chest computed tomography( CT) at preoperative check for gastric cancer.
Metastatic lung tumor was suspected, and partial resection of the right lung was
performed. Histopathologic examination revealed papillary proliferation lined by
endothelial cells and a hematoma. Immunohistochemically, the endothelial cells
were positive for CD31/CD34 and factor VIII related antigen.
PMID- 25137321
TI - [New prosthesis implant technique of aortic root abscess; circumferential
transmural sutures].
AB - A patient with aortic root abscess was successfully treated with a newly
developed suture technique named "circumferential transmural sutures". This
suture technique provides 1)a tight attachment of the prosthesis to the aortic
wall and 2)a secure healing of infection by exposure of the abscess cavity to
blood flow without complicated procedures. This technique would be a useful
alternative for the aortic root abscess without left ventriculo-aortic
disruption.
PMID- 25137322
TI - [Initial report of uniportal video-assisted thoracoscopic lobectomy in Japan].
AB - To date, more than 100 reports of several major pulmonary resections through a
uniportal approach have been published. However, there have been no reports of
uniportal thoracoscopic lobectomy in Japan. We present herein a successful case
of uniportal thoracoscopic right lower lobectomy through a 3.5-cm incision for 84
year-old female patient with primary lung cancer (clinical stage I A).
Postoperative course was uneventful and she discharged from the hospital on day 5
postoperatively. Pathological diagnosis was primary adenocarcinoma of T1aN0M0,
stage I A.
PMID- 25137323
TI - [Pediatric case of congenital coronary artery fistula; surgical result and late
changes in coronary artery aneurysm].
AB - Congenital coronary artery fistula is an uncommon heart anomaly involving the
coronary arteries. We report here a case of a 4-year-old boy who had a coronary
fistula from the right coronary artery to the right ventricle, with a coronary
aneurysm. He was asymptomatic, but the calculated ratio of pulmonary blood flow
to systemic blood flow was shown to be high [pulmonary flow (Qp)/systemic
flow(Qs)=1.78]. The coronary angiography showed that the right coronary artery
was dilated beginning at the ostium and had an aneurysm at the acute marginal
portion. A large spherical aneurysm approximately 20 mm in diameter was found to
have been connected with coronary fistula opening into the right ventricle.
Surgical repair by closure of the fistula under direct vision, partial resection
and suture closure of the aneurysm was performed. Plication of the proximal
portion of the right coronary artery was not performed, and the diffusely dilated
artery was left untouched. After this operation, he recovered well under
anticoagulant treatment with warfarin and aspirin. Postoperative angiography was
performed 17 months after the surgery to evaluate morphological changes in the
coronary artery. The angiography confirmed the closure of the fistula and the
regression of coronary artery dilatation.
PMID- 25137324
TI - [Pulmonary non-tuberculous mycobacteriosis complicated with lung cancer].
AB - A 54-year-old man with pulmonary non-tuberculous mycobacteriosis( pulmonary NTM)
who had been treated by antituberculous chemotherapy, developed a new nodule of
1.3 cm in size in the segment 1/2 of the right upper lobe. The cavity of 3.5 cm
in size in the segment 6 of the right lower lobe from which Mycobacterium
intracellulare was bronchoscopically detected, was suspected to be pulmonary NTM
lesion. Since lung cancer was highly suspected by radiological examinations,
right upper lobectomy and S6 segmentectomy were performed. Pathological diagnosis
for the right upper lobe nodule was adenocarcinoma.
PMID- 25137325
TI - [Pulmonary actinomycosis that was difficult to make an accurate diagnosis].
AB - A 35-year-old man was referred to our hospital, because of recurrent pneumonia.
His chest X-ray film and computed tomography showed mass-like consolidation with
a cavity in the right upper lobe. He underwent a bronchoscopic examination, but
no diagnosis was established. Therefore a surgical biopsy was performed, but the
pathological findings revealed that it was only an inflammatory change without
any malignant component. For a while, antibiotic and the steroid treatment was
continued resulting in the aggravation of clinical findings. Finally, an upper
lobe excision was performed for the complete excision of the lesion. As a result
of pathology, pulmonary actinomycosis was diagnosed.
PMID- 25137326
TI - [Purtscher's retinopathy following blunt chest compression].
AB - Following chest or abdominal injury, acute blurring of vision occurs without
direct eye injury. This disease is known as Purtscher's retinopathy. A 74-year
old man suffered blunt chest injury by air bag inflation at traffic accident.
Next morning, he suddenly complained of visual abnormality. An ophthalmoscopy
revealed multiple cotton-wool exudation and retinal edema. He was diagnosed as
Purtscher's retinopathy. The symptoms of soft exudation and retinal edema
gradually resolved. The visual acuity gradually improved, but not reached to the
previous level. We must be aware of this retinopathy, since this is rare but
sometimes sight-threatening condition.
PMID- 25137330
TI - [Successful excision of a left ventricular fibroma in an adult patient; report of
a case].
AB - A 55-year-old man was referred with a diagnosis of a left ventricular thrombus.
Echocardiography revealed that he had a thrombus in the free wall of the left
ventricle. Under cardiopulmonary bypass, we removed the intramural tumor. After
the removal, the defect was repaired by Dor operation. Pathological examination
revealed the tumor was a cardiac fibroma. He is doing well without any troubles 3
years after the operation.
PMID- 25137331
TI - [Adult endocardial blood cyst; report of a case].
AB - We report herein a rare case of endocardial blood cyst (EBC) in an adult patient.
A 63-year-old asymptomatic woman underwent echocardiography, which incidentally
detected a cardiac tumor in the right atrium. On echocardiography, the tumor was
revealed to be a 30-mm round mass with thin, hyperechogenic walls and
heterogeneously hypoechogenic contents. The lesion was attached to the septum. On
computed tomography, the tumor appeared partly calcified and showed poor contrast
enhancement. On magnetic resonance imaging, the lesion appeared isointense or
slightly hyperintense in T1 and T2-weighted sequences. Myxoma was strongly
suspected based on these preoperative imaging findings. The tumor was
successfully excised under cardiopulmonary bypass. Gross examination confirmed
that the cyst was filled with blood. The cystic walls comprised thin-layered
fibrous tissue lined with endocardial cells. No tumor cells were found. The
diagnosis of EBC was confirmed based on histopathological examination, and the
postoperative course was uneventful.
PMID- 25137332
TI - [Bilateral pulmonary artery occlusion due to primary pulmonary artery sarcoma;
report of a case].
AB - 60-year-old female who complained of severe dyspnea was admitted with a diagnosis
of massive pulmonary embolism. An emergency operation was undertaken due to right
side heart failure. Under extracorporeal circulation with beating heart, large,
white and smooth surface mass which was originated from right pulmonary artery
was removed. Pathology of the mass showed low differentiated sarcoma. No evidence
of other primary lesion by positron emission tomography-computed tomography (PET
CT) suggested primary pulmonary artery sarcoma. We scheduled total resection of
the right lung, however postoperative CT showed large mass occupying from right
pulmonary artery to main pulmonary trunk. Palliative chemo radiation therapy was
introduced. Pulmonary artery sarcoma mimicking pulmonary thromboembolism is so
malignant that the diagnosis and treatment should not be delayed.
PMID- 25137334
TI - [Successful treatment using thoracic endovascular aortic repair (TEVAR) to
mycotic aortic aneurysm; report of a case].
AB - We describe a case with mycotic aneurysm in a descending thoracic aorta. We
applied thoracic endovascular aortic repair (TEVAR) technique to that aortic
aneurysm after administering the high dose antibiotics and controlling the
infection. Postoperative course was uneventful and he was in a good condition.
PMID- 25137335
TI - [Surgical treatment for infective prosthetic mitral valve endocarditis with
cardiogenic shock; report of a case].
AB - We report a surgical case of active infective prosthetic mitral valve
endocarditis with cardiogenic shock. The causative organism was methicillin
resistant coagulase negative Staphylococci (MRCNS) During medical treatment, the
prosthetic valve was abruptly detouched partially from the mitral annulus, and
the patient developed rapid hemodynamic deterioration. We performed emergency re
do mitral valve replacement. The postoperative course was uneventful. Rapid
establishment of femoro-femoral bypass was very effective for the emergency re-do
valve surgery.
PMID- 25137336
TI - [Bridge to recovery with ventricular assist device support for eosinophilic
myocarditis].
AB - A 39-year-old man initially presented with cough, fever, and shortness of breath.
His symptom got worse gradually, and he was admitted to a nearby hospital.
Echocardiography revealed a dilated left ventricle and severe left ventricular
dysfunction. Despite inotropic and intra-aortic balloon pumping (IABP) support,
the patient developed cardiogenic shock with fever of unknown origin, followed by
multi-organ failure. A left-ventricular assist device (LVAD) was implanted.
Pathologic evaluation showed an extensive eosinophil-rich inflammatory
infiltrate, and consistent with the diagnosis of eosinophilic myocarditis. After
high-dose steroid administration, the cardiac function improved and explantation
of the LVAD was successfully performed. The patient was discharged and remains
well at the 24-month follow-up.
PMID- 25137337
TI - [Pulmonary metastasis from breast cancer 38 years after mastectomy; report of a
case].
AB - A 76-year-old woman with a history of radical mastectomy for cancer of the right
breast 38 years previously developed a solitary right lung nodule which was a
metastasis from breast cancer. Diagnosis of the cause of a solitary pulmonary
nodule is usually difficult in a patient with a history of extrapulmonary
malignancy. A solitary pulmonary metastasis from breast cancer with a disease
free interval of longer than 15 years has been quite rarely reported. We describe
an unusual case of a solitary pulmonary metastasis from breast cancer 38 years
after the initial treatment.
PMID- 25137338
TI - [An operative case of thymic cyst with thymoma;report of a case].
AB - Thymic cyst with thymoma is a rare disease. A 67-year-old woman was referred to
our hospital for right chest pain and cough. Mass shadow in the right hilum was
detected in the chest radiograph. Chest computed tomography( CT) revealed a
cystic mass with partially thickened wall suggesting solid tumor at the anterior
mediastinum. The tumor was resected by median sternotomy. Histopathological
finding was a multilocular thymic cyst with thymoma of spindle cell type.
PMID- 25137339
TI - [Hemopneumothorax after thoracic sympathetic nerve block; report of a case].
AB - A 72-year-old man, who had been treated pneumothorax 50 years ago, visited a
physician complaining of dyspnea after thoracic sympathetic nerve block for
postherpetic neuralgia. The patient was diagnosed as pneumothorax, and was
consulted to our hospital. Clinical sign and the chest radiography suggested
tension hemopneumothorax, and the chest drainage was immediately performed.
Although bloody fluid of 1,100 ml was initially drained, no further increase was
noted. The patient was discharged on the 21st hospital day.
PMID- 25137341
TI - Effects of tea intake on blood pressure: a meta-analysis of randomised controlled
trials.
AB - The effect of tea intake on blood pressure (BP) is controversial. We performed a
meta-analysis of randomised controlled trials to determine the changes in
systolic and diastolic BP due to the intake of black and green tea. A systematic
search was conducted in MEDLINE, EMBASE and the Cochrane Controlled Trials
Register up to May 2014. The weighted mean difference was calculated for net
changes in systolic and diastolic BP using fixed-effects or random-effects
models. Previously defined subgroup analyses were performed to explore the
influence of study characteristics. A total of twenty-five eligible studies with
1476 subjects were selected. The acute intake of tea had no effects on systolic
and diastolic BP. However, after long-term tea intake, the pooled mean systolic
and diastolic BP were lower by - 1.8 (95 % CI - 2.4, - 1.1) and - 1.4 (95 % CI -
2.2, - 0.6) mmHg, respectively. When stratified by type of tea, green tea
significantly reduced systolic BP by 2.1 (95 % CI - 2.9, - 1.2) mmHg and
decreased diastolic BP by 1.7 (95 % CI - 2.9, - 0.5) mmHg, and black tea showed a
reduction in systolic BP of 1.4 (95 % CI - 2.4, - 0.4) mmHg and a decrease in
diastolic BP of 1.1 (95 % CI - 1.9, - 0.2) mmHg. The subgroup analyses showed
that the BP-lowering effect was apparent in subjects who consumed tea more than
12 weeks (systolic BP - 2.6 (95 % CI - 3.5, - 1.7) mmHg and diastolic BP - 2.2
(95 % CI - 3.0, - 1.3) mmHg, both P< 0.001). The present findings suggest that
long-term ( >= 12 weeks) ingestion of tea could result in a significant reduction
in systolic and diastolic BP.
PMID- 25137342
TI - Does antibiotic use affect childhood asthma rates in China?
PMID- 25137340
TI - Quantitative susceptibility mapping (QSM) of white matter multiple sclerosis
lesions: Interpreting positive susceptibility and the presence of iron.
AB - PURPOSE: Within multiple sclerosis (MS) lesions iron is present in chronically
activated microglia. Thus, iron detection with MRI might provide a biomarker for
chronic inflammation within lesions. Here, we examine contributions of iron and
myelin to magnetic susceptibility of lesions on quantitative susceptibility
mapping (QSM). METHODS: Fixed MS brain tissue was assessed with MRI including
gradient echo data, which was processed to generate field (phase), R2* and QSM.
Five lesions were sectioned and evaluated by immunohistochemistry for presence of
myelin, iron and microglia/macrophages. Two of the lesions had an elemental
analysis for iron concentration mapping, and their phospholipid content was
estimated from the difference in the iron and QSM data. RESULTS: Three of the
five lesions had substantial iron deposition that was associated with microglia
and positive susceptibility values. For the two lesions with elemental analysis,
the QSM derived phospholipid content maps were consistent with myelin labeled
histology. CONCLUSION: Positive susceptibility values with respect to water
indicate the presence of iron in MS lesions, although both demyelination and iron
deposition contribute to QSM.
PMID- 25137343
TI - Asthma prevalence among Hispanic adults in Puerto Rico and Hispanic adults of
Puerto Rican descent in the United States - results from two national surveys.
AB - Abstract Objective: To assess whether asthma prevalence differs between Hispanic
adults living in Puerto Rico and Hispanic adults of Puerto Rican descent living
in the United States. METHODS: We used 2008-2010 Behavioral Risk Factor
Surveillance System data, administered in Puerto Rico for Hispanic adults living
in Puerto Rico (Hispanics in Puerto Rico), and 2008-2010 National Health
Interview Survey data for Hispanic adults of Puerto Rican descent living in the
United States (Puerto Rican Americans). We used 95% confidence intervals (CIs) to
compare asthma prevalence between corresponding subgroups; non-overlapping CIs
indicate statistical significance. Chi-square test and multivariate logistic
regression were used to assess the association between current asthma status and
socio-demographic factors and health risk behaviors within each Puerto Rican
population. RESULTS: Current asthma prevalence among Hispanics in Puerto Rico
(7.0% [6.4%-7.7%]) was significantly lower than the prevalence among Puerto Rican
Americans (15.6% [13.0%-18.1%]). The prevalence among almost all socio
demographic and health risk subgroups of Hispanics in Puerto Rico was
significantly lower than the prevalence among the corresponding subgroups of
Puerto Rican Americans. Adjusting for potential confounders did not alter the
results. Asthma prevalence was significantly associated with obesity among Puerto
Rican Americans (adjusted prevalence ratios [aPR]=1.5 [1.1-2.0]), and among
Hispanics in Puerto Rico was associated with obesity (aPR=1.6 [1.3-1.9]), smoking
(aPR=1.4 [1.1-1.9]) and being female (aPR=1.9 [1.5-2.4]). CONCLUSION: Asthma was
more prevalent among Puerto Rican Americans than Hispanics in Puerto Rico.
Although the observed associations did not explain all variations in asthma
prevalence between these two populations, they may lay the foundation for future
research.
PMID- 25137344
TI - Symptoms after removal of ureteral stents.
AB - BACKGROUND AND PURPOSE: Urology practices frequently encounter individuals who
experience various degrees of pain/discomfort after ureteral stent removal. These
symptoms have been previously proved to greatly affect functionality,
convalescence time, quality of life, and healthcare costs. The etiology is
unclear, but the condition is often self-limiting. We counsel individuals on
their risk of having post-ureteral stent removal pain based on anecdotal data. We
sought to evaluate the incidence of post-ureteral stent removal pain and attempt
to find the probable cause. PATIENTS AND METHODS: All individuals who had a
ureteral stent placed and subsequently removed for various etiologies (between
January 2012 and May 2013) were evaluated by filling a survey conducted by a
member of the healthcare team 1 to 3 weeks after ureteral stent removal.
Univariate and multivariate analysis were used to assess correlation between
demographics, operative procedures, convalescent time, and post-ureteral stent
removal symptoms. All statistical analyses were performed using SAS((r))
software, and a P value of less than 0.05 was considered to indicate statistical
significance. RESULTS: Of the 104 individuals in the final cohort, 64% had
symptoms after stent removal (pain, hematuria, frequency, urgency, or fever), and
among those with symptoms, 60% experienced pain/discomfort. On univariate
analysis, stone basketing and indwelling stent discomfort correlated positively
with pain after stent removal. On the other hand, the use of anticholinergics and
a longer indwelling stent duration were associated with less pain after stent
removal. On multivariate analysis, correlation with procedures involving basket
extraction and indwelling stent discomfort maintained significance. CONCLUSION:
Our series suggests that two of three individuals who undergo ureteral stent
removal experience symptoms thereafter. Individuals undergoing stone basket
extraction and those who experienced stent discomfort were more likely to have
pain after stent removal. Anticholinergic use and stents indwelling for a longer
time were associated with less pain after stent removal.
PMID- 25137345
TI - Attenuation of anti-tuberculosis therapy induced hepatotoxicity by Spirulina
fusiformis, a candidate food supplement.
AB - Therapy using Isoniazid (INH) and Rifampicin (RIF) leads to induction of
hepatotoxicity in some individuals undergoing anti-tuberculosis treatment. In
this study, we assessed the effect of Spirulina fusiformis on INH and RIF induced
hepatotoxicity in rats compared with hepatoprotective drug Silymarin. Induction
of hepatotoxicity was measured by changes in the liver marker enzymes (aspartate
transaminase, alanine transaminase, and alkaline phosphatase). The antioxidant
status was also analyzed in liver tissue homogenate and plasma by measurement of
superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase,
and lipid peroxidation levels. We also aimed to study the binding and
interactions of the transcription factors Pregnane X Receptor (PXR) and Farnesoid
X Receptor (FXR) with INH, RIF, and representative active compounds of Spirulina
fusiformis by in silico methods. The administration of INH and RIF resulted in
significant (p < 0.05) decrease in the antioxidant levels and total protein
levels. There was also a significant (p < 0.05) increase in the levels of liver
marker enzymes. Spirulina fusiformis was seen to protect the parameters from
significant changes upon challenge with INH and RIF in a dose-dependent manner.
This was corroborated by histological examination of the liver. The results of
the in silico analyses further support the wet lab results.
PMID- 25137346
TI - Clinical and pathologic characteristics of intranasal abuse of combined opioid
acetaminophen medications.
AB - BACKGROUND: The nonmedical abuse of prescription opioids via intranasal
administration is a growing problem. The objective of this study is to
investigate of the typical presentation of intranasal opioid-acetaminophen abuse
and outline optimal therapy. METHODS: This study was a retrospective chart
review. Patients with intranasal pathology from inhalation of combined opioid
acetaminophen medications (COAMs) from 3 academic otolaryngology practices in
western Pennsylvania from January 2012 to October 2012 were included in the
review. RESULTS: Seven adults ranging in age from 23 to 46 years were identified
with nasal complaints from the intranasal inhalation of COAMs. All patients
presented with nasal pain and were found to have fibrinous necrotic nasal mucosa
involving the posterior nasal cavity and nasopharynx. Of the 7 patients, 6
(85.7%) presented with a septal perforation. Pathology and culture revealed
fungus in 85.7% of the patients; however, no invasive fungal disease was noted in
any of the specimens. Patients did not improve with either systemic or topical
antifungal therapy. Polarizable material characteristic of talc used as a tablet
binder was present in the histopathology of 4 of 7 (57.1%) patients. Patients who
abstained from intranasal drug use along with serial debridement demonstrated the
greatest improvement. CONCLUSION: Intranasal COAM abuse causes nasal pain, tissue
necrosis with potential septal and palatal perforation, and noninvasive fungal
colonization. Antifungal therapy was of no benefit in the current series of
patients. Current therapy should focus on recognition of the etiology of
patients' pathology and encourage abstinence from intranasal use of these drugs
along with serial debridements.
PMID- 25137350
TI - Hydrogen bonding networks tune proton-coupled redox steps during the enzymatic
six-electron conversion of nitrite to ammonia.
AB - Multielectron multiproton reactions play an important role in both biological
systems and chemical reactions involved in energy storage and manipulation. A key
strategy employed by nature in achieving such complex chemistry is the use of
proton-coupled redox steps. Cytochrome c nitrite reductase (ccNiR) catalyzes the
six-electron seven-proton reduction of nitrite to ammonia. While a catalytic
mechanism for ccNiR has been proposed on the basis of studies combining
computation and crystallography, there have been few studies directly addressing
the nature of the proton-coupled events that are predicted to occur along the
nitrite reduction pathway. Here we use protein film voltammetry to directly
interrogate the proton-coupled steps that occur during nitrite reduction by
ccNiR. We find that conversion of nitrite to ammonia by ccNiR adsorbed to
graphite electrodes is defined by two distinct phases; one is proton-coupled, and
the other is not. Mutation of key active site residues (H257, R103, and Y206)
modulates these phases and specifically alters the properties of the detected
proton-dependent step but does not inhibit the ability of ccNiR to conduct the
full reduction of nitrite to ammonia. We conclude that the active site residues
examined are responsible for tuning the protonation steps that occur during
catalysis, likely through an extensive hydrogen bonding network, but are not
necessarily required for the reaction to proceed. These results provide important
insight into how enzymes can specifically tune proton- and electron transfer
steps to achieve high turnover numbers in a physiological pH range.
PMID- 25137351
TI - Inhibitory effects of butein on cancer metastasis and bioenergetic modulation.
AB - Tumor metastasis is the major obstacle for cancer treatment. Previous studies
have shown that butein exhibits antiangiogenesis property and anticancer effects
in different kinds of human cancer cells. However, the effects of butein on
metastasis and energy metabolism of cancer cells are mostly unknown. This study
showed that butein significantly inhibited invasion of cancer cells without
acting in a cytotoxic fashion. It was further demonstrated that butien
dramatically suppressed cancer metastasis by an in vivo CAM-intravasation model.
Additionally, butein concentration-dependently repressed the expression and
activity of matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen
activator (uPA). The study indicated that butein may repress MMP-9 and uPA
proteolytic activities and subsequently inhibit cancer metastasis via
Akt/mTOR/p70S6K translational machinery. Moreover, butein may partly suppress
cancer metastasis by down-regulating ATP synthesis via both oxidative and
glycolytic metabolism. The results suggest that butein is a potential
antimetastatic agent worthy of further development for cancer treatment.
PMID- 25137352
TI - Sensitive electrochemical sensors for simultaneous determination of ascorbic
acid, dopamine, and uric acid based on Au@Pd-reduced graphene oxide
nanocomposites.
AB - Sensitive electrochemical sensors were fabricated with reduced graphene oxide
supported Au@Pd (Au@Pd-RGO) nanocomposites by one-step synthesis for individual
and simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric
acid (UA) with low detection limits and wide concentration ranges. From the Au@Pd
RGO-modified electrodes, well-separated oxidation peaks and enhanced peak
currents of AA, DA, and UA were observed owing to the superior conductivity of
RGO and the excellent catalytic activity of Au@Pd nanoparticles. For individual
detection, the linear responses of AA, DA, and UA were in the concentration
ranges of 0.1-1000, 0.01-100, and 0.02-500 MUM with detection limits of 0.02,
0.002, and 0.005 MUM (S/N = 3), respectively. For simultaneous detection by
synchronous change of the concentrations of AA, DA, and UA, the linear response
ranges were 1-800, 0.1-100, and 0.1-350 MUM with detection limits of 0.28, 0.024,
and 0.02 MUM (S/N = 3), respectively. The fabricated sensors were further applied
to the detection of AA, DA, and UA in urine samples. The Au@Pd-RGO nanocomposites
have promising applications in highly sensitive and selective electrochemical
sensing.
PMID- 25137354
TI - A three-step process to facilitate the annulation of polycyclic aromatic
hydrocarbons.
AB - A new efficient three-step process to annulate polycyclic aromatic hydrocarbons
(PAHs) has been developed, providing access to PAHs with saturated rings that
under current chemical methods would be difficult to produce in an efficient
manner. This method relies on a palladium-catalyzed cross-coupling reaction of
various brominated PAHs with cyclohexanone to yield alpha-arylated ketones, which
are converted to regiospecific vinyl triflates and cyclized by a palladium
catalyzed intramolecular arene-vinyl triflate coupling to produce PAHs with
incorporated saturated rings or "tetrahydroindeno-annulated" PAHs.
PMID- 25137353
TI - Perturbation of long-range water dynamics as the mechanism for the antifreeze
activity of antifreeze glycoprotein.
AB - Very little is known about the mechanism of antifreeze action of antifreeze
glycoproteins (AFGPs) present in Antarctic teleost fish. Recent NMR and CD
studies assisted with total synthesis of synthetic AFGP variants have provided
insight into the structure of short AFGP glycopeptides, though the observations
did not yield information on the antifreeze mechanism of action. In this study,
we use Hamiltonian replica exchange (HREX) molecular dynamics simulations to
probe the structure and surrounding aqueous environments of both the natural
(AFGP8) and synthetic (s-AFGP4) AFGPs. AFGPs can adopt both amphiphilic and
pseudoamphiphilic conformations, the preference of which is related to the
proline content of the peptide. The arrangement of carbohydrates allows the
hydroxyl groups on terminal galactose units to form stable water bridges which in
turn influence the hydrogen-bond network, structure, and dynamics of the
surrounding solvent. Interestingly, these local effects lead to the perturbation
of the tetrahedral environment for water molecules in hydration layers far (10.0
12.0 A) from the AFGPs. This structure-induced alteration of long-range hydration
dynamics is proposed to be the major contributor to antifreeze activity, a
conclusion that is in line with terahertz spectroscopy experiments. The detailed
structure-mechanism correlation provided in this study could lead to the design
of better synthetic AFGP variants.
PMID- 25137356
TI - A statewide survey of adult and pediatric outpatient palliative care services.
AB - BACKGROUND: Outpatient palliative care services can improve patient outcomes, yet
little is known about their structure and characteristics. OBJECTIVE: To describe
the structure and characteristics of outpatient palliative care services
associated with California hospitals. DESIGN: Electronic survey.
SETTING/SUBJECTS: All 377 acute care hospitals in California. MEASUREMENTS:
Outpatient palliative care services structure and operational characteristics,
including staffing, clinical availability, and funding. RESULTS: Overall 96%
(361/377) of hospitals responded. Of the 136 hospitals with an adult palliative
care service, 18% (n=24) reported an outpatient palliative care service with a
mean age of 3.7 years. Of the 42 hospitals offering pediatric palliative care
services, 19% (n=8) reported an outpatient palliative care service with a mean
age of 3.4 years. On average, adult outpatient palliative care services see 159
new patients per year with 722 follow-up visits. Pediatric outpatient palliative
care services see 10 new patients per year with 28 follow-up visits. The average
staffing of adult outpatient palliative care services is 2.1 full-time equivalent
(FTE; range, 0.2-12) and for pediatric outpatient palliative care services 0.7
FTE (range, 0.1-2.0). Adult outpatient palliative care services operate a mean of
3.9 days per week compared to 1.1 days per week for pediatric outpatient
palliative care services. Few services provided 24/7 coverage (25% adult, 38%
pediatric). Wait times for newly referred patients were 11 days for adults and 9
days for pediatrics. Most referrals are received from oncology (adult=47%,
pediatric=43%). Funding for outpatient palliative care services is largely
through institutional support (adult=80%, pediatric=62%), followed by foundations
(adult=10.3%, pediatric=23%), billing (adult=8.8%, pediatric=0%), and
philanthropy (adult=0.9%, pediatric=15%). Compared to similar data from 2007, the
prevalence of outpatient palliative care services affiliated with hospitals in
California has not changed significantly. CONCLUSIONS: Few California hospitals
offer outpatient palliative care services. This finding has remained consistent
over time. Adult and pediatric outpatient palliative care services care primarily
for patients with cancer, operate part-time with modest staffing, and are funded
primarily by their institution. Making the case for value to engender more
institutional support, increasing billing revenue, system initiatives, and
partnering with insurers may lead to the establishment of more outpatient
palliative care services.
PMID- 25137357
TI - Synthesis, detailed characterization, and theoretical understanding of
mononuclear chromium(III)-containing polyoxotungstates [Cr(III)(HX(V)W7O28)2]13-
(X = P, As) with exceptionally large magnetic anisotropy.
AB - Two monochromium(III)-containing heteropolytungstates, [Cr(III)(HP(V)W7O28)2](13
) (1a) and [Cr(III)(HAs(V)W7O28)2](13-) (2a), were prepared via simple, one-pot
reactions in aqueous, basic medium, by reaction of the composing elements, and
then isolated as hydrated sodium salts, Na13[Cr(III)(HP(V)W7O28)2].47H2O (1) and
Na13[Cr(III)(HAs(V)W7O28)2].52H2O (2). Polyanions 1a and 2a comprise an
octahedrally coordinated Cr(III) ion, sandwiched by two {PW7} or {AsW7} units.
Both compounds 1 and 2 were fully characterized in the solid state by single
crystal XRD, IR spectroscopy, thermogravimetric and elemental analyses, magnetic
susceptibility, and EPR measurements. Magnetic studies on 1 and 2 demonstrated
that both compounds exhibit appreciable deviation from typical paramagnetic
behavior, and have a ground state S = 3/2, as expected for a Cr(III) ion, but
with an exceptionally large zero-field uniaxial anisotropy parameter (D). EPR
measurements on powder and single-crystal samples of 1 and 2 using 9.5, 34.5, and
239.2 GHz frequencies and over 4-295 K temperature fully support the
magnetization results and show that D = +2.4 cm(-1), the largest and sign
assigned D-value so far reported for an octahedral Cr(III)-containing, molecular
compound. Ligand field analysis of results from CASSCF and NEVPT2-correlated
electronic structure calculations on Cr(OH)6(3-) model complexes allowed to
unravel the crucial role of the second coordination sphere of Cr(III) for the
unusually large magnetic anisotropy reflected by the experimental value of D. The
newly developed theoretical modeling, combined with the synthetic procedure for
producing such unusual magnetic molecules in a well-defined and essentially
magnetically isolated environment, appears to be a versatile new research area.
PMID- 25137358
TI - Amino acids as chiral auxiliaries in cyanuric chloride-based chiral derivatizing
agents for enantioseparation by liquid chromatography.
AB - This review summarizes and critically evaluates the recent research on
application of amino acids and amino acid amides as chiral auxiliaries in
cyanuric chloride (CC) based chiral derivatizing agents (CDRs), used in the
indirect approach for enantiomeric resolution. Methods of synthesis of such CDRs,
methods for synthesis of diastereomers of a variety of racemic compounds and
parameters of liquid chromatographic separation, along with their prospects and
their limitations in indirect enantioresolution, are discussed. Application of
the said CDR(s) and the technical approach to be used that are discussed should
be beneficial for control of enantiomeric purity in pharmaceutical industry,
verification of enantiomeric ratio of commercial formulations and the development
of methods for indirect resolution of a variety of chiral compounds.
Derivatization methods are particularly required when a chromophore is to be
introduced in low UV absorbing molecules, for their detection.
PMID- 25137359
TI - Reconstructing Austronesian population history in Island Southeast Asia.
AB - Austronesian languages are spread across half the globe, from Easter Island to
Madagascar. Evidence from linguistics and archaeology indicates that the
'Austronesian expansion,' which began 4,000-5,000 years ago, likely had roots in
Taiwan, but the ancestry of present-day Austronesian-speaking populations remains
controversial. Here, we analyse genome-wide data from 56 populations using new
methods for tracing ancestral gene flow, focusing primarily on Island Southeast
Asia. We show that all sampled Austronesian groups harbour ancestry that is more
closely related to aboriginal Taiwanese than to any present-day mainland
population. Surprisingly, western Island Southeast Asian populations have also
inherited ancestry from a source nested within the variation of present-day
populations speaking Austro-Asiatic languages, which have historically been
nearly exclusive to the mainland. Thus, either there was once a substantial
Austro-Asiatic presence in Island Southeast Asia, or Austronesian speakers
migrated to and through the mainland, admixing there before continuing to western
Indonesia.
PMID- 25137365
TI - Development of an organic lateral resolution test device for imaging mass
spectrometry.
AB - An organic lateral resolution test device has been developed to measure the
performance of imaging mass spectrometry (IMS) systems. The device contains
periodic gratings of polyethylene glycol (PEG) and lipid bars covering a wide
range of spatial frequencies. Microfabrication technologies were employed to
produce well-defined chemical interfaces, which allow lateral resolution to be
assessed using the edge-spread function (ESF). In addition, the design of the
device allows for the direct measurement of the modulation transfer function
(MTF) to assess image quality. Scanning electron microscopy (SEM) and time-of
flight secondary ion mass spectrometry (TOF-SIMS) were used to characterize the
device. TOF-SIMS imaging was used to measure the chemical displacement of
biomolecules in matrix-assisted laser desorption/ionization (MALDI) matrix
crystals. In a proof-of-concept experiment, the platform was also used to
evaluate MALDI matrix application methods, specifically aerosol spray and
sublimation methods.
PMID- 25137366
TI - Reconciling "stress" and "health" in physical anthropology: what can
bioarchaeologists learn from the other subdisciplines?
AB - The concepts of "stress" and "health" are foundational in physical anthropology
as guidelines for interpreting human behavior and biocultural adaptation in the
past and present. Though related, stress and health are not coterminous, and
while the term "health" encompasses some aspects of "stress," health refers to a
more holistic condition beyond just physiological disruption, and is of
considerable significance in contributing to anthropologists' understanding of
humanity's lived experiences. Bioarchaeological interpretations of human health
generally are made from datasets consisting of skeletal markers of stress,
markers that result from (chronic) physiological disruption (e.g., porotic
hyperostosis; linear enamel hypoplasia). Non-specific indicators of stress may
measure episodes of stress and indicate that infection, disease, or nutritional
deficiencies were present in a population, but in assessing these markers,
bioarchaeologists are not measuring "health" in the same way as are human
biologists, medical anthropologists, or primatologists. Rather than continue to
diverge on separate (albeit parallel) trajectories, bioarchaeologists are advised
to pursue interlinkages with other subfields within physical anthropology toward
bridging "stress" and "health." The papers in this special symposium set include
bioarchaeologists, human biologists, molecular anthropologists, and
primatologists whose research develops this link between the concepts of "stress"
and "health," encouraging new avenues for bioarchaeologists to consider and
reconsider health in past human populations.
PMID- 25137367
TI - Effect of prolonged sitting and breaks in sitting time on endothelial function.
AB - Sitting time (ST) is associated with cardiovascular disease risk factors, whereas
breaking ST has been reported to be beneficial for reducing cardiovascular risk.
PURPOSE: The objective of this study is to examine the effects of breaking ST on
superficial femoral artery (SFA) endothelial function. HYPOTHESES: 1) Prolonged
sitting would induce endothelial dysfunction and changes in shear forces, and 2)
breaking ST with brief periods of activity would prevent attenuation in
endothelial function. METHODS: Twelve nonobese men (24.2 +/- 4.2 yr) participated
in two randomized 3-h sitting trials. In the sitting (SIT) trial, subjects were
seated on a firmly cushioned chair for 3 h without moving their lower
extremities. In the breaking ST trial (ACT), subjects sat similar to the SIT
trial but walked on a treadmill for 5 min at 2 mph at 30 min, 1 h 30 min, and 2 h
30 min during the sitting interval. SFA flow-mediated dilation (FMD) was assessed
at baseline, 1 h, 2 h, and 3 h in each trial. Statistical analyses were performed
using dependent variables SFA FMD and shear rates. Significance was set at P <=
0.05. RESULTS: In the SIT trial, there was a significant decline in SFA FMD from
baseline to 3 h (baseline, 4.72% +/- 3.78%; 1 h, 0.52% +/- 0.85%; 2 h, 1.66% +/-
1.11%; 3 h, 2.2% +/- 2.15; P < 0.05 by ANOVA) accompanied by a decline in mean
shear rate and antegrade shear rate but no difference in shear rate (area under
the curve). By two-way repeated-measures ANOVA, ACT prevented the sitting-induced
decline in FMD (baseline, 4.5% +/- 2.3%; 1 h, 5.04% +/- 2.85%; 2 h, 5.28% +/-
5.05%; 3 h, 6.9% +/- 4.5%) along with no decline in shear rates. CONCLUSION:
Three hours of sitting resulted in a significant impairment in shear rate and SFA
FMD. When light activity breaks were introduced hourly during sitting, the
decline in FMD was prevented.
PMID- 25137368
TI - Eccentric hamstring strength and hamstring injury risk in Australian footballers.
AB - PURPOSE: Are eccentric hamstring strength and between-limb imbalance in eccentric
strength, measured during the Nordic hamstring exercise, risk factors for
hamstring strain injury (HSI)? METHODS: Elite Australian footballers (n = 210)
from five different teams participated. Eccentric hamstring strength during the
Nordic exercise was obtained at the commencement and conclusion of preseason
training and at the midpoint of the season. Injury history and demographic data
were also collected. Reports on prospectively occurring HSI were completed by the
team medical staff. Relative risk (RR) was determined for univariate data, and
logistic regression was employed for multivariate data. RESULTS: Twenty-eight new
HSI were recorded. Eccentric hamstring strength below 256 N at the start of the
preseason and 279 N at the end of the preseason increased the risk of future HSI
2.7-fold (RR, 2.7; 95% confidence interval, 1.3 to 5.5; P = 0.006) and 4.3-fold
(RR, 4.3; 95% confidence interval, 1.7 to 11.0; P = 0.002), respectively. Between
limb imbalance in strength of greater than 10% did not increase the risk of
future HSI. Univariate analysis did not reveal a significantly greater RR for
future HSI in athletes who had sustained a lower limb injury of any kind within
the last 12 months. Logistic regression revealed interactions between both
athlete age and history of HSI with eccentric hamstring strength, whereby the
likelihood of future HSI in older athletes or athletes with a history of HSI was
reduced if an athlete had high levels of eccentric strength. CONCLUSION: Low
levels of eccentric hamstring strength increased the risk of future HSI.
Interaction effects suggest that the additional risk of future HSI associated
with advancing age or previous injury was mitigated by higher levels of eccentric
hamstring strength.
PMID- 25137370
TI - Low-frequency severe-intensity interval training improves cardiorespiratory
functions.
AB - PURPOSE: The present study investigated the effects of severe-intensity interval
training at a frequency of once a week on cardiorespiratory function at rest and
during exercise. METHODS: Fourteen young healthy males were randomly assigned to
either an interval training group or control group. Cardiorespiratory function
was investigated by incremental maximal exercise test and constant work rate
submaximal exercise test before and after the intervention period in all
subjects. Submaximal exercise test was conducted at two work rates (80%
ventilatory threshold (VT) level and 100% VT level plus 50% of the difference
between VT and peak oxygen consumption (VO2)) for 8 min; the same work rates and
duration were used before and after training. Left ventricular adaptations were
assessed by echocardiography under supine resting conditions before and after
training. In the interval training group, seven subjects performed cycle
ergometer training once per week for 3 months. The training consisted of three
bouts of exercises to volitional fatigue at 80% maximum work rate. RESULTS:
Increased VO2max (+13%, P = 0.015), VT (+21%, P = 0.001), and left ventricular
posterior wall thickness (+18%, P = 0.002) and reduced minute ventilation (-12%,
P = 0.032) and blood lactate concentration (-16%, P = 0.025) during high
intensity exercise were observed after the training program compared with
baseline. Although not significant, VO2 and cycling economy (VO2 per work rate)
during high-intensity exercise decreased slightly after training. CONCLUSION: The
present results indicate that severe-intensity interval training, even when
performed at a low frequency, markedly improves cardiorespiratory function as
well as induces cardiac morphological adaptations involving left ventricular
hypertrophy and cardiorespiratory metabolic response during submaximal exercise.
The present findings may provide new insights for low-frequency, severe-intensity
interval training in the field of sports science.
PMID- 25137369
TI - Accelerometer adherence and performance in a cohort study of US Hispanic adults.
AB - PURPOSE: This study described participant adherence to wearing the accelerometer
and accelerometer performance in a cohort study of adults. METHODS: From 2008 to
2011, 16,415 US Hispanic/Latino adults age 18-74 yr enrolled in the Hispanic
Community Health Study/Study of Latinos. Immediately after the baseline visit,
participants wore an Actical accelerometer for 1 wk. This study explored
correlates of accelerometer participation and adherence, defined as wearing it
for at least three of a possible six days for >=10 h.d. Accelerometer performance
was assessed by exploring the number of different values of accelerometer counts
per minute for each participant. RESULTS: Overall, 92.3% (n = 15,153) had at
least 1 d with accelerometer data and 77.7% (n = 12,750) were adherent. Both
accelerometer participation and adherence were higher among participants who were
married or partnered, reported a higher household income, were first-generation
immigrants, or reported lower sitting time. Participation was also higher among
those with no stair limitations. Adherence was higher among participants who were
male, older, employed or retired, not US born, preferred Spanish over English,
reported higher work activity or lower recreational activity, and with a lower
body mass index. Among the sample that met the adherence definition, the maximum
recorded count per minute was 12,000, and there were a total of 5846 different
counts per minute. On average, participants had 112.5 different counts per minute
over 6 d (median, 106; interquartile range, 91-122). The number of different
counts per minute was higher among men, younger ages, normal weight, and those
with higher accelerometer-assessed physical activity. CONCLUSION: Several
correlates differed between accelerometer participation and adherence. These
characteristics could be targeted in future studies to improve accelerometer
wear. The performance of the accelerometer provided insight into creating a more
accurate nonwear algorithm.
PMID- 25137372
TI - Long-term fertilization modifies the structures of soil fulvic acids and their
binding capability with Al.
AB - The binding characteristics of organic ligands and minerals in fulvic acids (FAs)
with Al are essential for understanding soil C sequestration, remain poorly
understood. In this study, Fourier transform infrared (FTIR) spectroscopy
combined with two-dimensional correlation spectroscopy (2DCOS) analysis was
applied for the first time to explore the binding of Al with organic ligands and
minerals in soil FAs. For these analyses, two contrasting treatments were
selected from a long-term (i.e., 22-year) fertilization experiment: chemical
(NPK) fertilization and swine manure (SM) fertilization. The results showed that
the long-term application of organic and inorganic fertilizers to soils had
little effect on the compositions of the fluorescent substances and organic
ligands in the soil FAs. However, long-term SM fertilization increased the
weathered Al and Si concentrations in the soil FAs compared with long-term
chemical fertilization. Furthermore, organic ligands in the soil FAs were mainly
bound with Al in the NPK treatment, whereas both organic ligands and minerals (Al
O-Si, Si-O) were bound with Al under the M fertilization conditions. Both
transmission electron microscopy (TEM) images and X-ray diffraction spectra
demonstrated that amorphous and short-range-ordered nanominerals were abundant in
the soil FAs from the SM plot in contrast to the soil FAs from the NPK plot. This
result illustrates the role nanominerals play in the preservation of soil FAs by
during long-term organic fertilization. In summary, the combination of FTIR and
2D correlation spectroscopy is a promising approach for the characterization of
the binding capability between soil FAs and Al, and a better understanding FA-Al
binding capability will greatly contribute to global C cycling.
PMID- 25137373
TI - Functional networks of nucleocytoplasmic transport-related genes differentiate
ischemic and dilated cardiomyopathies. A new therapeutic opportunity.
AB - Heart failure provokes alterations in the expression of nucleocytoplasmic
transport-related genes. To elucidate the nucleocytoplasmic transport-linked
functional network underlying the two major causes of heart failure, ischemic
cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), we examined global
transcriptome profiles of left ventricular myocardium tissue samples from 31
patients (ICM, n = 10; DCM, n = 13) undergoing heart transplantation and control
donors (CNT, n = 8) using RNA-Sequencing and GeneMANIA. Comparative profiling of
ICM versus control and DCM versus control showed 1081 and 2440 differentially
expressed genes, respectively (>1.29-fold; P<0.05). GeneMANIA revealed
differentially regulated functional networks specific to ICM and DCM. In
comparison with CNT, differential expression was seen in 9 and 12
nucleocytoplasmic transport-related genes in ICM and DCM groups, respectively.
DDX3X, KPNA2, and PTK2B were related to ICM, while SMURF2, NUP153, IPO5, RANBP3,
NOXA1, and RHOJ were involved in DCM pathogenesis. Furthermore, the two
pathologies shared 6 altered genes: XPO1, ARL4, NFKB2, FHL3, RANBP2, and RHOU
showing an identical trend in expression in both ICM and DCM. Notably, the core
of the derived functional networks composed of nucleocytoplasmic transport
related genes (XPO1, RANBP2, NUP153, IPO5, KPNA2, and RANBP3) branched into
several pathways with downregulated genes. Moreover, we identified genes whose
expression levels correlated with left ventricular mass index and left
ventricular function parameters in HF patients. Collectively, our study provides
a clear distinction between the two pathologies at the transcriptome level and
opens up new possibilities to search for appropriate therapeutic targets for ICM
and DCM.
PMID- 25137375
TI - Discovery of covalent inhibitors of glyceraldehyde-3-phosphate dehydrogenase, a
target for the treatment of malaria.
AB - We developed a new class of covalent inhibitors of Plasmodium falciparum
glyceraldehyde-3-phosphate dehydrogenase, a validated target for the treatment of
malaria, by screening a small library of 3-bromo-isoxazoline derivatives that
inactivate the enzyme through a covalent, selective bond to the catalytic
cysteine, as demonstrated by mass spectrometry. Substituents on the isoxazolinic
ring modulated the potency up to 20-fold, predominantly due to an electrostatic
effect, as assessed by computational analysis.
PMID- 25137374
TI - The ginsenoside 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol induces
autophagy and apoptosis in human melanoma via AMPK/JNK phosphorylation.
AB - Studies have shown that a major metabolite of the red ginseng ginsenoside Rb1,
called 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (GPD), exhibits
anticancer properties. However, the chemotherapeutic effects and molecular
mechanisms behind GPD action in human melanoma have not been previously
investigated. Here we report the anticancer activity of GPD and its mechanism of
action in melanoma cells. GPD, but not its parent compound Rb1, inhibited
melanoma cell proliferation in a dose-dependent manner. Further investigation
revealed that GPD treatment achieved this inhibition through the induction of
autophagy and apoptosis, while Rb1 failed to show significant effect at the same
concentrations. The inhibitory effect of GPD appears to be mediated through the
induction of AMPK and the subsequent attenuation of mTOR phosphorylation. In
addition, GPD activated c-Jun by inducing JNK phosphorylation. Our findings
suggest that GPD suppresses melanoma growth by inducing autophagic cell death and
apoptosis via AMPK/JNK pathway activation. GPD therefore has the potential to be
developed as a chemotherapeutic agent for the treatment of human melanoma.
PMID- 25137376
TI - Susceptibility-weighted imaging in heat stroke.
AB - OBJECTIVE: To assess the role of susceptibility-weighted imaging in the detection
of intracranial hemorrhage after heat stroke and in the prognosis. MATERIALS AND
METHODS: The study group consisted of eight patients after heat stroke, with a
score of 3 to 9 in Glasgow Coma Scale. The MR studies were performed with a 1.5 T
scanner. Susceptibility-weighted imaging data were collected within 2-5 days
after heat stroke. The study was approved by ethics committee, and written
informed consents were obtained from family members of the patients. RESULTS:
Punctate hemorrhages were detected in brain stem, corona radiata and frontal lobe
by susceptibility-weighted imaging for three patients. Among the three cases, two
patients came to death in the 5th day and the 25th day after heat stroke
respectively. Another patient became a persistent vegetative state and died about
3 months later. Five patients with no hemorrhage detected gradually recovered and
cerebellar dysfunction remained to various degrees. CONCLUSIONS: Heat stroke is a
life-threatening condition characterized by hyperthermia and accompanied by
various complications such as disseminated intravascular coagulation.
Susceptibility-weighted imaging is a very useful tool for detection of
intracranial hemorrhage and may probably evaluate the prognosis after heat
stroke.
PMID- 25137377
TI - Central venous-to-arterial CO2-gap may increase in severe isovolemic anemia.
AB - Despite blood transfusions are administered to restore adequate tissue
oxygenation, transfusion guidelines consider only hemoglobin as trigger value,
which gives little information about the balance between oxygen delivery and
consumption. Central venous oxygen saturation is an alternative, however its
changes reflect systemic metabolism and fail to detect regional hypoxia. A
complementary parameter to ScvO2 may be central venous-to-arterial carbon dioxide
difference (CO2-gap). Our aim was to investigate the change of alternative
transfusion trigger values in experimental isovolemic anemia. After splenectomy,
anesthetized Vietnamese mini pigs (n = 13, weight range: 18-30 kg) underwent
controlled bleeding in five stages (T1-T5). During each stage approximately 10%
of the estimated starting total blood volume was removed and immediately replaced
with an equal volume of colloid. Hemodynamic measurements and blood gas analysis
were then performed. Each stage of bleeding resulted in a significant fall in
hemoglobin, the O2-extraction increased significantly from T3 and ScvO2 showed a
similar pattern and dropped below the physiological threshold of 70% at T4. By T4
CO2-gap increased significantly and well correlated with VO2/DO2 and ScvO2. To
our knowledge, this is the first study to show that anemia caused altered oxygen
extraction may have an effect on CO2-gap.
PMID- 25137378
TI - Can POCIS be used in Water Framework Directive (2000/60/EC) monitoring networks?
A study focusing on pesticides in a French agricultural watershed.
AB - In this study, the main current limitations in the application of the Polar
Organic Chemical Integrative Sampler (POCIS) in regulatory monitoring programmes
were evaluated. POCIS were exposed from March to December by successive periods
of 14 days in the River Trec (Lot et Garonne, France) and analysed for 34
pesticides. The study of the uncertainty related to the POCIS data was performed
and we concluded that it might be up to 138%, which is higher than European Union
requirements but this issue was adequately counterbalanced by the gain of
temporal representativeness. Comparison with data from the official monitoring
programme from the French Water Agency showed that the POCIS is already suitable
for both operational and investigative monitoring. The sampled fraction issue,
and then compliance with Environmental Quality Standards, was also addressed. It
was confirmed that POCIS samples only the dissolved fraction of dimethenamid and
showed that for compounds like atrazine, desethylatrazine and metolachlor, the
POCIS concentration is equivalent to the whole water concentration. For
dimethenamid, which exhibited a tendency to adsorb on suspended matter, a method
was suggested to assess the raw water concentration from the POCIS measure.
Finally, an innovative procedure for using passive sampler data for compliance
checks in the framework of surveillance monitoring is proposed.
PMID- 25137379
TI - The impact of organochlorines and metals on wild fish living in a tropical
hydroelectric reservoir: bioaccumulation and histopathological biomarkers.
AB - This study evaluates the contaminants in water and their bioaccumulation in the
gills and liver of two ecologically distinct fish species, Astyanax fasciatus and
Pimelodus maculatus, living in the reservoir of the Furnas hydroelectric power
station located in Minas Gerais in the southeastern Brazil. The histological
alterations in these organs are also examined. Water and fish were collected in
June and December from five sites (site 1: FU10, site 2: FU20, site 3: FU30, site
4: FU40 and site 5: FU50) in the reservoir, and agrochemicals and metals selected
based on their use in the field crops surrounding the reservoir were analyzed in
the water and in the fish gills and livers. The concentrations of the
organochlorines aldrin/dieldrin, endosulfan and heptachlor/heptachlor epoxide as
well as the metals copper, chromium, iron and zinc in the gills and livers of
both fish species were higher in June than in December; the liver accumulated
higher concentrations of contaminants than the gills. The organochlorine
metolachlor was detected only in the liver. The histological pattern of changes
was similar in both species with regard to contaminant accumulation in the gills
and liver. Fish from FU10, the least contaminated site, exhibited normal gill
structure and moderate to heavy liver damage. Fish collected at FU20 to FU50,
which were contaminated with organochlorines and metals, showed slight to
moderate gill damage in June and irreparable liver damage in the livers in June
and December. The histological changes in the gills and liver were suitable to
distinguishing contaminated field sites and are therefore useful biomarkers for
environmental contamination representing a biological end-point of exposure.
PMID- 25137380
TI - A multi-level biological approach to evaluate impacts of a major municipal
effluent in wild St. Lawrence River yellow perch (Perca flavescens).
AB - The development of integrated ecotoxicological approaches is of great interest in
the investigation of global concerns such as impacts of municipal wastewater
effluents on aquatic ecosystems. The objective of this study was to investigate
the effects of a major wastewater municipal effluent on fish using a multi-level
biological approach, from gene transcription and enzyme activities to
histological changes. Yellow perch (Perca flavescens) were selected based on
their wide distribution, their commercial and recreational importance, and the
availability of a customized microarray. Yellow perch were sampled upstream of a
major municipal wastewater treatment plant (WWTP) and 4 km and 10 km downstream
from its point of discharge in the St. Lawrence River (Quebec, Canada).
Concentrations of perfluoroalkyl substances (PFASs), polybrominated diphenyl
ethers (PBDEs) and metals/trace elements in whole body homogenates were
comparable to those from other industrialized regions of the world. Genomic
results indicated that the transcription level of 177 genes was significantly
different (p<0.024) between exposed and non-exposed fish. Among these genes, 38
were found to be differentially transcribed at both downstream sites. Impacted
genes were associated with biological processes and molecular functions such as
immunity, detoxification, lipid metabolism/energy homeostasis (e.g., peroxisome
proliferation), and retinol metabolism suggesting impact of WWTP on these
systems. Moreover, antioxidant enzyme activities were more elevated in perch
collected at the 4 km site. Biomarkers of lipid metabolism, biosynthetic
activity, and aerobic capacities were significantly lower (p<0.05) in fish
residing near the outfall of the effluent. Histological examination of the liver
indicated no differences between sites. Correlations between PFAS, PBDE, and
metal/trace element tissue concentrations and markers of peroxisomal
proliferation, oxidative stress, and retinoid metabolism were found at the gene
and cellular levels. Present results suggest that relating transcriptomic
analyses to phenotypic responses is important to better understand impacts of
environmental contamination on wild fish populations.
PMID- 25137381
TI - Antimony in the soil-water-plant system at the Su Suergiu abandoned mine
(Sardinia, Italy): strategies to mitigate contamination.
AB - This study was aimed to implement the understanding of the Sb behavior in near
surface environments, as a contribution to address appropriate mitigation actions
at contaminated sites. For this purpose, geochemical data of soil (8 sites),
water (29 sites), and plant (12 sites) samples were collected. The study area is
located at Su Suergiu and surroundings in Sardinia (Italy), an abandoned mine
area heavily contaminated with Sb, with relevant impact on water bodies that
supply water for agriculture and domestic uses. Antimony in the soil horizons
ranged from 19 to 4400 mg kg(-1), with highest concentrations in soils located
close to the mining-related wastes, and concentrations in the topsoil much higher
than in the bedrock. The Sb readily available fraction was about 2% of the total
Sb in the soil. Antimony in the pore water ranged from 23 to 1700 MUg L(-1), with
highest values in the Sb-rich soils. The waters showed neutral to slightly
alkaline pH, redox potential values indicating oxidizing conditions, electrical
conductivity in the range of 0.2 to 3.7 mS cm(-1), and dissolved organic carbon
<=2 mg L(-1). The waters collected upstream of the mine have Ca-bicarbonate
dominant composition, and median concentration of Sb(tot) of 1.7 MUg L(-1) (that
is total antimony determined in waters filtered through 0.45 MUm), a value
relatively high as compared with the background value (<=0.5 MUg L(-1) Sb)
estimated for Sardinian waters, but below the limits established by the European
Union and the World Health Organization for drinking water (5 MUg L(-1) Sb and 20
MUg L(-1) Sb, respectively). The waters flowing in the mine area are
characterized by Ca-sulfate dominant composition, and median concentrations of
7000 MUg L(-1) Sb(tot). Extreme concentrations, up to 30,000 MUg L(-1) Sb(tot),
were observed in waters flowing out of the slag materials derived from the
processing of Sb-ore. The Sb(III) was in the range of 0.8 to 760 MUg L(-1) and
represented up to 6% of Sb(tot). In the waters collected downstream of the mine,
median Sb(tot) concentrations decreased as distance from the mine area increases:
1300 MUg L(-1) Sb(tot) in the stream Rio Ciurixeda at 3 km distance, and 25 MUg
L(-1) Sb(tot) in the main River Flumendosa 15 km further downstream. Attenuation
of Sb contamination was mainly due to dilution. Results of modeling, carried out
by both EQ3 and Visual MINTEQ computer programs, suggest that sorption of
dissolved Sb onto solid phases, and/or precipitation of Sb-bearing minerals,
likely give a minor contribution to attenuation of Sb contamination. The slightly
alkaline pH and oxidizing conditions might favor the persistence of inorganic
Sb(V)-bearing species at long distance in the studied waters. Concentrations of
Sb in the plants Pistacia lentiscus and Asparagus ranged from 0.1 to 22 mg kg(
1), with maximum values in plants growing very close to the mining-related
wastes. The P. lentiscus grows well on the soils highly contaminated with Sb at
Su Suergiu and might be used for revegetation of the Sb-rich heaps, thus
contributing to reduce the dispersion of contaminated materials. Major effects of
contamination were observed on the water bodies located downstream of the Su
Suergiu abandoned mine. The maximum load (16.6 kg Sb per day) to the Flumendosa,
the main aquatic recipient, was observed after heavy rain events. Therefore,
priorities of mitigation actions should be focused on minimizing the contact of
rain and runoff waters on the heaps of mining wastes.
PMID- 25137382
TI - Impact of fresh organic matter incorporation on PAH fate in a contaminated
industrial soil.
AB - The impacts of fresh organic matter (OM) incorporation in an industrial PAH
contaminated soil on its structure and contaminant concentrations (available and
total) were monitored. A control soil and a soil amended with the equivalent of
10 years maize residue input were incubated in laboratory-controlled conditions
over 15 months. The structure of the amended soil showed an aggregation process
trend which is attributable to (i) the enhanced microbial activity resulting from
fresh OM input itself and (ii) the fresh OM and its degradation products.
Initially the added organic matter was evenly distributed among all
granulodensimetric fractions, and then rapidly degraded in the sand fraction,
while stabilizing and accumulating in the silts. PAH degradation remained slight,
despite the enhanced microbial biomass activity, which was similar to kinetics of
the turnover rate of OM in an uncontaminated soil. The silts stabilized the
anthropogenic OM and associated PAH. The addition of fresh OM tended to
contribute to this stabilization process. Thus, in a context of plant growth on
this soil two opposing processes might occur: rhizodegradation of the available
contaminant and enhanced stabilization of the less available fraction due to
carbon input.
PMID- 25137383
TI - Comparative study on PCDD/F pollution in soil from the Antarctic, Arctic and
Tibetan Plateau.
AB - The concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans
(PCDFs) in 35 soil samples collected from Fildes Peninsula in the Antarctic, Ny
Alesund in the Arctic, and Zhangmu-Nyalam in the Tibetan Plateau were reported in
this study. A comparison of the total concentration and TEQ of PCDD/Fs at the
Three Poles was conducted. Both the total concentration and TEQ of PCDD/Fs
demonstrates a decreasing trend in the order of Zhangmu-Nyalam (mean: 26.22 pg/g,
0.37 pg I-TEQ/g)>Ny-Alesund (mean: 9.97 pg/g, 0.33 pg I-TEQ/g)>Fildes Peninsula
(mean: 2.18 pg/g, 0.015 pg I-TEQ/g) (p<0.05). In all samples, the congener and
homologue profiles dominated with higher (seven and eight) chlorinated PCDD/Fs
(more than 85% of the total mass percentage of PCDD/Fs) at the Three Poles.
Finally, a FLEXPART backward simulation was used to preliminarily identify the
potential local and regional anthropogenic sources of PCDD/Fs. The results imply
that the air masses passing over surrounding regions with significant PCDD/F
emissions might contribute to the occurrence of PCDD/Fs in both the Arctic and
Tibetan Plateau.
PMID- 25137384
TI - Advanced hybrid supercapacitor based on a mesoporous niobium pentoxide/carbon as
high-performance anode.
AB - Recently, hybrid supercapacitors (HSCs), which combine the use of battery and
supercapacitor, have been extensively studied in order to satisfy increasing
demands for large energy density and high power capability in energy-storage
devices. For this purpose, the requirement for anode materials that provide
enhanced charge storage sites (high capacity) and accommodate fast charge
transport (high rate capability) has increased. Herein, therefore, a preparation
of nanocomposite as anode material is presented and an advanced HSC using it is
thoroughly analyzed. The HSC comprises a mesoporous Nb2O5/carbon (m-Nb2O5-C)
nanocomposite anode synthesized by a simple one-pot method using a block
copolymer assisted self-assembly and commercial activated carbon (MSP-20) cathode
under organic electrolyte. The m-Nb2O5-C anode provides high specific capacity
with outstanding rate performance and cyclability, mainly stemming from its
enhanced pseudocapacitive behavior through introduction of a carbon-coated
mesostructure within a voltage range from 3.0 to 1.1 V (vs Li/Li(+)). The HSC
using the m-Nb2O5-C anode and MSP-20 cathode exhibits excellent energy and power
densities (74 W h kg(-1) and 18,510 W kg(-1)), with advanced cycle life (capacity
retention: ~90% at 1000 mA g(-1) after 1000 cycles) within potential range from
1.0 to 3.5 V. In particular, we note that the highest power density (18,510 W kg(
1)) of HSC is achieved at 15 W h kg(-1), which is the highest level among similar
HSC systems previously reported. With further study, the HSCs developed in this
work could be a next-generation energy-storage device, bridging the performance
gap between conventional batteries and supercapacitors.
PMID- 25137385
TI - DNA nanoparticles with core-shell morphology.
AB - Mannobiose-modified polyethylenimines (PEI) are used in gene therapy to generate
nanoparticles of DNA that can be targeted to the antigen-presenting cells of the
immune system. We report that the sugar modification alters the DNA organization
within the nanoparticles from homogenous to shell-like packing. The depth
dependent packing of DNA within the nanoparticles was probed using AFM nano
indentation. Unmodified PEI-DNA nanoparticles display linear elastic properties
and depth-independent mechanics, characteristic of homogenous materials.
Mannobiose-modified nanoparticles, however, showed distinct force regimes that
were dependent on indentation depth, with 'buckling'-like response that is
reproducible and not due to particle failure. By comparison with theoretical
studies of spherical shell mechanics, the structure of mannobiosylated particles
was deduced to be a thin shell with wall thickness in the order of few
nanometers, and a fluid-filled core. The shell-core structure is also consistent
with observations of nanoparticle denting in altered solution conditions, with
measurements of nanoparticle water content from AFM images, and with images of
DNA distribution in Transmission Electron Microscopy.
PMID- 25137387
TI - A reliable and efficient protocol for human pluripotent stem cell differentiation
into the definitive endoderm based on dispersed single cells.
AB - Differentiation of pluripotent cells into endoderm-related cell types initially
requires in vitro gastrulation into the definitive endoderm (DE). Most
differentiation protocols are initiated from colonies of pluripotent cells
complicating their adaption due to insufficiently defined starting conditions.
The protocol described here was initiated from a defined cell number of dispersed
single cells and tested on three different human embryonic stem cell lines and
one human induced pluripotent stem cell line. Combined activation of
ActivinA/Nodal signaling and GSK3 inhibition for the first 24 h, followed by
ActivinA/Nodal signaling efficiently induced the DE state. Activation of
ActivinA/Nodal signaling alone was not effective. Efficient GSK3 inhibition
allowed the reduction of the ActivinA concentration during the entire protocol. A
feeder-independent cultivation of pluripotent cells was preferred to achieve the
high efficiency and robustness since feeder cells hindered the differentiation
process. Additionally, inhibition of the phosphatidylinositol 3-kinase (PI3K)
signaling pathway was not required, nonetheless yielding high cell numbers
efficiently committed toward the DE. Finally, the endoderm generated could be
differentiated further into PDX1-positive pan-pancreatic cells and NGN3-positive
endocrine progenitors. Thus, this efficient and robust DE differentiation
protocol is a step forward toward better reproducibility due to the well-defined
conditions based on dispersed single cells from feeder-free-cultivated human
pluripotent cells.
PMID- 25137386
TI - Associations between stroke mortality and weekend working by stroke specialist
physicians and registered nurses: prospective multicentre cohort study.
AB - BACKGROUND: Observational studies have reported higher mortality for patients
admitted on weekends. It is not known whether this "weekend effect" is modified
by clinical staffing levels on weekends. We aimed to test the hypotheses that
rounds by stroke specialist physicians 7 d per week and the ratio of registered
nurses to beds on weekends are associated with mortality after stroke. METHODS
AND FINDINGS: We conducted a prospective cohort study of 103 stroke units (SUs)
in England. Data of 56,666 patients with stroke admitted between 1 June 2011 and
1 December 2012 were extracted from a national register of stroke care in
England. SU characteristics and staffing levels were derived from cross-sectional
survey. Cox proportional hazards models were used to estimate hazard ratios (HRs)
of 30-d post-admission mortality, adjusting for case mix, organisational,
staffing, and care quality variables. After adjusting for confounders, there was
no significant difference in mortality risk for patients admitted to a stroke
service with stroke specialist physician rounds fewer than 7 d per week (adjusted
HR [aHR] 1.04, 95% CI 0.91-1.18) compared to patients admitted to a service with
rounds 7 d per week. There was a dose-response relationship between weekend
nurse/bed ratios and mortality risk, with the highest risk of death observed in
stroke services with the lowest nurse/bed ratios. In multivariable analysis,
patients admitted on a weekend to a SU with 1.5 nurses/ten beds had an estimated
adjusted 30-d mortality risk of 15.2% (aHR 1.18, 95% CI 1.07-1.29) compared to
11.2% for patients admitted to a unit with 3.0 nurses/ten beds (aHR 0.85, 95% CI
0.77-0.93), equivalent to one excess death per 25 admissions. The main limitation
is the risk of confounding from unmeasured characteristics of stroke services.
CONCLUSIONS: Mortality outcomes after stroke are associated with the intensity of
weekend staffing by registered nurses but not 7-d/wk ward rounds by stroke
specialist physicians. The findings have implications for quality improvement and
resource allocation in stroke care. Please see later in the article for the
Editors' Summary.
PMID- 25137389
TI - Modulation of gephyrin-glycine receptor affinity by multivalency.
AB - Gephyrin is a major determinant for the accumulation and anchoring of glycine
receptors (GlyRs) and the majority of gamma-aminobutyric acid type A receptors
(GABAARs) at postsynaptic sites. Here we explored the interaction of gephyrin
with a dimeric form of a GlyR beta-subunit receptor-derived peptide. A 2 A
crystal structure of the C-terminal domain of gephyrin (GephE) in complex with a
15-residue peptide derived from the GlyR beta-subunit defined the core binding
site, which we targeted with the dimeric peptide. Biophysical analyses via
differential scanning calorimetry (DSC), thermofluor, and isothermal titration
calorimetry (ITC) demonstrated that this dimeric ligand is capable of binding
simultaneously to two receptor binding sites and that this multivalency results
in a 25-fold enhanced affinity. Our study therefore suggests that the oligomeric
state of gephyrin and the number of gephyrin-binding subunits in the pentameric
GABAARs and GlyRs together control postsynaptic receptor clustering.
PMID- 25137390
TI - Crystal structure of the mouse interleukin-3 beta-receptor: insights into
interleukin-3 binding and receptor activation.
AB - Interleukin-3 (IL-3) is a cytokine secreted by mast cells and activated T-cells
known to be an important regulator of differentiation, survival, proliferation
and activation of a range of haemopoietic lineages. The effects of IL-3 on target
cells are mediated by a transmembrane receptor system composed of a cytokine
specific alpha-subunit and a beta-subunit, the principal signalling entity. In
the mouse, two beta-subunits have co-evolved: a common beta-subunit (betac)
shared between IL-3 and the related cytokines IL-5 and granulocyte/macrophage
colony-stimulating factor (GM-CSF); and an IL-3-specific beta-subunit (betaIL-3).
betaIL-3 differs from betac in its specificity for IL-3 and its capacity to bind
IL-3 directly in the absence of an alpha-subunit, and, in the absence of
structural information, the basis for these properties has remained enigmatic. In
the present study, we have solved the crystal structure of the betaIL-3
ectodomain at 3.45 A (1 A=0.1 nm) resolution. This structure provides the first
evidence that betaIL-3 adopts an arch-shaped intertwined homodimer with similar
topology to the paralogous betac structure. In contrast with apo-betac, however,
the ligand-binding interface of betaIL-3 appears to pre-exist in a conformation
receptive to IL-3 engagement. Molecular modelling of the IL-3-betaIL-3 interface,
in conjunction with previous mutational studies, suggests that divergent
evolution of both betaIL-3 and IL-3 underlies their unique capacity for direct
interaction and specificity.
PMID- 25137391
TI - Composite-walled magnetic microcapsules at the water-toluene interface by ligand
polymerization.
AB - The liquid-liquid interface has been exploited as a platform for devising gold
and iron oxide nanoparticle (NP)-decorated composite microcapsules (MCs) by cross
linking between -OH groups of poly(ethylene glycol) (PEG) attached to the iron
oxide (Fe3O4) nanoparticle surface and starch attached to the gold (Au)
nanoparticle surface in the presence of terephthaloyl chloride as a cross-linker.
These nanoparticle-decorated capsules form a shell of both types of nanoparticles
with water as the minor phase and toluene as the major phase. The morphology of
these capsules has been characterized by optical, transmission, and scanning
electron microscopy images, and the polymerization reaction has been established
by UV-vis and FTIR spectroscopic studies. The magnetic behavior of the capsules
has been illustrated by using an external magnetic field to tailor the magnetic
control of the capsules. The encapsulated phase was impregnated with dye
molecules of three different sizes, viz., fluorescein isothiocyanate and its
dextran conjugates, to investigate the permeability of the capsule wall by
fluorescence spectroscopy. Interestingly, the microcapsules exhibit size
selective permeability across the capsule wall that points to their plausible
applications in controlled encapsulation and release.
PMID- 25137392
TI - Estimating risks and relative risks in case-base studies under the assumptions of
gene-environment independence and Hardy-Weinberg equilibrium.
AB - Many diseases result from the interactions between genes and the environment. An
efficient method has been proposed for a case-control study to estimate the
genetic and environmental main effects and their interactions, which exploits the
assumptions of gene-environment independence and Hardy-Weinberg equilibrium. To
estimate the absolute and relative risks, one needs to resort to an alternative
design: the case-base study. In this paper, the authors show how to analyze a
case-base study under the above dual assumptions. This approach is based on a
conditional logistic regression of case-counterfactual controls matched data. It
can be easily fitted with readily available statistical packages. When the dual
assumptions are met, the method is approximately unbiased and has adequate
coverage probabilities for confidence intervals. It also results in smaller
variances and shorter confidence intervals as compared with a previous method for
a case-base study which imposes neither assumption.
PMID- 25137393
TI - Dynamic analysis and pattern visualization of forest fires.
AB - This paper analyses forest fires in the perspective of dynamical systems. Forest
fires exhibit complex correlations in size, space and time, revealing features
often present in complex systems, such as the absence of a characteristic length
scale, or the emergence of long range correlations and persistent memory. This
study addresses a public domain forest fires catalogue, containing information of
events for Portugal, during the period from 1980 up to 2012. The data is analysed
in an annual basis, modelling the occurrences as sequences of Dirac impulses with
amplitude proportional to the burnt area. First, we consider mutual information
to correlate annual patterns. We use visualization trees, generated by
hierarchical clustering algorithms, in order to compare and to extract
relationships among the data. Second, we adopt the Multidimensional Scaling (MDS)
visualization tool. MDS generates maps where each object corresponds to a point.
Objects that are perceived to be similar to each other are placed on the map
forming clusters. The results are analysed in order to extract relationships
among the data and to identify forest fire patterns.
PMID- 25137395
TI - Transformation of oxcarbazepine and human metabolites of carbamazepine and
oxcarbazepine in wastewater treatment and sand filters.
AB - Carbamazepine (CBZ) and oxcarbazepine (OXC) are widely used anticonvulsants that
are extensively metabolized in the human body. The pharmaceuticals and their
human metabolites are present in influents and effluents of wastewater treatment
plants (WWTPs), in rivers and streams, and in drinking water. In this study, the
biodegradation of OXC and its main human metabolite, 10-hydroxy-CBZ (10OHCBZ),
and the main human metabolite of CBZ, 10,11-dihydro-10,11-dihydroxy-CBZ
(DiOHCBZ), was investigated in contact with activated sludge from a wastewater
treatment plant (WWTP) and sand filter material from a waterworks. The
transformation of DiOHCBZ, 10OHCBZ, and OXC led to the formation of the following
main TPs: 1-(2-benzoic acid)-(1H,3H)-quinazoline-2,4-dione (BaQD), 1-(2-benzoic
acid)-(1H,3H)-quinazoline-2-one (BaQM), 9-aldehyde-acridine, 9-carboxylic acid
acridine (9-CA-ADIN), hydroxyl 9-CA-ADIN, acridone (ADON), 11-keto-OXC, and 2,2'
(carbamoylazanediyl)dibenzoic acid. TP formation could be explained by three
proposed transformation pathways, including reactions such as oxidation, alpha
ketol rearrangement, or benzylic acid rearrangement. The results highlight the
fact that the TP abundances strongly depend on the concentrations spiked in the
lab-scale experiments. BaQD, 9-CA-ADIN, and ADON were detected in WWTP effluents,
rivers, and streams. 9-CA-ADIN was found at maximum concentrations in WWTP
effluent and rivers up to 920 +/- 50 ng L(-1) and 304 +/- 26 ng L(-1),
respectively. Even in drinking water, BaQD and 9-CA-ADIN were present at
concentrations of 26 +/- 2 ng L(-1) and 189 +/- 3 ng L(-1), respectively.
PMID- 25137394
TI - KRAS genotypic changes of circulating tumor cells during treatment of patients
with metastatic colorectal cancer.
AB - INTRODUCTION: Circulating tumor cells (CTCs) could represent a non-invasive
source of cancer cells used for longitudinal monitoring of the tumoral mutation
status throughout the course of the disease. The aims of the present study were
to investigate the detection of KRAS mutations in CTCs from patients with
metastatic colorectal cancer (mCRC) and to compare their mutation status during
treatment or disease progression with that of the corresponding primary tumors.
MATERIALS AND METHODS: Identification of the seven most common KRAS mutations on
codons 12 and 13 was performed by Peptide Nucleic Acid (PNA)-based qPCR method.
The sensitivity of the assay was determined after isolation of KRAS mutant cancer
cells spiked into healthy donors' blood, using the CellSearch Epithelial Cell
kit. Consistent detection of KRAS mutations was achieved in samples containing at
least 10 tumor cells/7.5 ml of blood. RESULTS: The clinical utility of the assay
was assessed in 48 blood samples drawn from 31 patients with mCRC. All patients
had PIK3CA and BRAF wild type primary tumors and 14 KRAS mutant tumors. CTCs were
detected in 65% of specimens obtained from 74% of patients. KRAS mutation
analysis in CTC-enriched specimens showed that 45% and 16.7% of patients with
mutant and wild type primary tumors, respectively, had detectable mutations in
their CTCs. Assessing KRAS mutations in serial blood samples revealed that
individual patient's CTCs exhibited different mutational status of KRAS during
treatment. CONCLUSIONS: The current findings support the rationale for using the
CTCs as a dynamic source of tumor cells which, by re-evaluating their KRAS
mutation status, could predict, perhaps more accurately, the response of mCRC
patients to targeted therapy.
PMID- 25137397
TI - Considerations for assessment of reproductive and developmental toxicity of
oligonucleotide-based therapeutics.
AB - This white paper summarizes the current consensus of the Reproductive
Subcommittee of the Oligonucleotide Safety Working Group on strategies to assess
potential reproductive and/or developmental toxicities of therapeutic
oligonucleotides (ONs). The unique product characteristics of ONs require
considerations when planning developmental and reproductive toxicology studies,
including (a) chemical characteristics, (b) assessment of intended and unintended
mechanism of action, and (c) the optimal exposure, including dosing regimen.
Because experience across the various classes of ONs as defined by their chemical
backbone is relatively limited, best practices cannot be defined. Rather, points
to consider are provided to help in the design of science-based reproductive
safety evaluation programs based upon product attributes.
PMID- 25137398
TI - CO2 deserts: implications of existing CO2 supply limitations for carbon
management.
AB - Efforts to mitigate the impacts of climate change will require deep reductions in
anthropogenic CO2 emissions on the scale of gigatonnes per year. CO2 capture and
utilization and/or storage technologies are a class of approaches that can
substantially reduce CO2 emissions. Even though examples of this approach, such
as CO2-enhanced oil recovery, are already being practiced on a scale >0.05
Gt/year, little attention has been focused on the supply of CO2 for these
projects. Here, facility-scale data newly collected by the U.S. Environmental
Protection Agency was processed to produce the first comprehensive map of CO2
sources from industrial sectors currently supplying CO2 in the United States.
Collectively these sources produce 0.16 Gt/year, but the data reveal the presence
of large areas without access to CO2 at an industrially relevant scale (>25
kt/year). Even though some facilities with the capability to capture CO2 are not
doing so and in some regions pipeline networks are being built to link CO2
sources and sinks, much of the country exists in "CO2 deserts". A life cycle
analysis of the sources reveals that the predominant source of CO2, dedicated
wells, has the largest carbon footprint further confounding prospects for
rational carbon management strategies.
PMID- 25137396
TI - Wood smoke enhances cigarette smoke-induced inflammation by inducing the aryl
hydrocarbon receptor repressor in airway epithelial cells.
AB - Our previous studies showed that cigarette smokers who are exposed to wood smoke
(WS) are at an increased risk for chronic bronchitis and reduced lung function.
The present study was undertaken to determine the mechanisms for WS-induced
adverse effects. We studied the effect of WS exposure using four cohorts of mice.
C57Bl/6 mice were exposed for 4 or 12 weeks to filtered air, to 10 mg/m(3) WS for
2 h/d, to 250 mg/m(3) cigarette smoke (CS) for 6 h/d, or to CS followed by WS
(CW). Inflammation was absent in the filtered air and WS groups, but enhanced by
twofold in the bronchoalveolar lavage of the CW compared with CS group as
measured by neutrophil numbers and levels of the neutrophil chemoattractant,
keratinocyte-derived chemokine. The levels of the anti-inflammatory lipoxin,
lipoxin A4, were reduced by threefold along with cyclo-oxygenase (COX)-2 and
microsomal prostaglandin E synthase (mPGES)-1 in airway epithelial cells and PGE2
levels in the bronchoalveolar lavage of CW compared with CS mice. We replicated,
in primary human airway epithelial cells, the changes observed in mice.
Immunoprecipitations showed that WS blocked the interaction of aryl hydrocarbon
receptor (AHR) with AHR nuclear transporter to reduce expression of COX-2 and
mPGES-1 by increasing expression of AHR repressor (AHRR). Collectively, these
studies show that exposure to low concentrations of WS enhanced CS-induced
inflammation by inducing AHRR expression to suppress AHR, COX-2, and mPGES-1
expression, and levels of PGE2 and lipoxin A4. Therefore, AHRR is a potential
therapeutic target for WS-associated exacerbations of CS-induced inflammation.
PMID- 25137399
TI - Optimal data systems: the future of clinical predictions and decision support.
AB - PURPOSE OF REVIEW: The purpose of the review is to describe the evolving concept
and role of data as it relates to clinical predictions and decision-making.
RECENT FINDINGS: Critical care medicine is, as an especially data-rich specialty,
becoming acutely cognizant not only of its historic deficits in data utilization
but also of its enormous potential for capturing, mining, and leveraging such
data into well-designed decision support modalities as well as the formulation of
robust best practices. SUMMARY: Modern electronic medical records create an
opportunity to design complete and functional data systems that can support
clinical care to a degree never seen before. Such systems are often referred to
as 'data-driven,' but a better term is 'optimal data systems' (ODS). Here we
discuss basic features of an ODS and its benefits, including the potential to
transform clinical prediction and decision support.
PMID- 25137400
TI - A history of outcome prediction in the ICU.
AB - PURPOSE OF REVIEW: There are few first-hand accounts that describe the history of
outcome prediction in critical care. This review summarizes the authors' personal
perspectives about the development and evolution of Acute Physiology and Chronic
Health Evaluation over the past 35 years. RECENT FINDINGS: We emphasize what we
have learned in the past and more recently our perspectives about the current
status of outcome prediction, and speculate about the future of outcome
prediction. SUMMARY: There is increasing evidence that superior accuracy in
outcome prediction requires complex modeling with detailed adjustment for
diagnosis and physiologic abnormalities. Thus, an automated electronic system is
recommended for gathering data and generating predictions. Support, either public
or private, is required to assist users and to update and improve models. Current
outcome prediction models have increasingly focused on benchmarks for resource
use, a trend that seems likely to increase in the future.
PMID- 25137401
TI - ICU severity of illness scores: APACHE, SAPS and MPM.
AB - PURPOSE OF REVIEW: This review aims to evaluate the latest versions of the Acute
Physiology and Chronic Health Evaluation, Simplified Acute Physiology Score and
Mortality Probability Model scores, make comparisons and describe their strengths
and limitations. Additionally, we provide critical analysis and recommendations
for the use of these scoring systems in different scenarios. RECENT FINDINGS: The
last generation of ICU scoring systems (Acute Physiology and Chronic Health
Evaluation IV, Mortality Probability Model 0-III (MPM0-III) and Simplified Acute
Physiology Score 3) was widely validated in different regions of the world and in
distinct settings comprising general ICU patients as well as specific subgroups
such as critically ill cancer patients, cardiovascular, surgical, acute kidney
injury requiring renal replacement therapy and those in need of extra-corporeal
membrane oxygen. Conflicting results are reported, and in general the scores
presented a good discrimination despite a worse calibration as compared with the
ones described in the original studies that generated them. Nonetheless, such
calibration is often improved when customizations are performed both at ICU and
region or country level. SUMMARY: ICU scoring systems provide a valuable
framework to characterize patients' severity of illness for the evaluation of ICU
performance, for quality improvement initiatives and for benchmarking purposes.
However, to ensure the best accuracy, constant updates as well as regional
customizations are required.
PMID- 25137402
TI - Is there still a role for low-dose dopamine use in acute heart failure?
AB - PURPOSE OF REVIEW: Acute heart failure (AHF) is a major health problem worldwide,
with no proven therapy. Low-dose dopamine has been used in this entity to improve
renal outcomes in the past decades. The aim of this article is to review the
former and recent clinical trials about the use of low-dose dopamine in AHF.
RECENT FINDINGS: The Dopamine in Acute Decompensated Heart Failure II study
enrolled 161 patients with AHF and found no improvement in clinical outcomes with
the addition of dopamine. Similarly, the Renal Optimization Strategies Evaluation
in Acute Heart Failure trial, which included 360 patients with AHF and renal
dysfunction, evaluated the efficacy of 72-h infusion of either low-dose
nesiritide or low-dose dopamine versus placebo in addition to standardized
diuretic treatment. No differences were found between both treatment groups and
placebo with regard to the coprimary endpoints of cumulative urine volume and
change from baseline in plasma cystatin C. SUMMARY: On the basis of the current
data, there is no role for the routine use of low-dose dopamine in nonhypotensive
patients with AHF. Further studies are needed to define the role of low-dose
dopamine in patients with AHF and hypotension. Until the availability of more
data, the use of dopamine in AHF should be individualized.
PMID- 25137403
TI - Predicting outcome in critical care: past, present and future.
PMID- 25137404
TI - (001) SrTiO3 | (001) MgO interface and oxygen-vacancy stability from first
principles calculations.
AB - In-depth understanding of interfacial atomistic structures is required to design
heterointerfaces with controlled functionalities. Using density functional theory
calculations, we investigate the interfacial structure of (001) SrTiO3 | (001)
MgO, and characterize the stable interface structure. Among the four types of
possible interface structures, we show that the TiO2-terminated SrTiO3 containing
electrostatically attractive Mg-O and Ti-O ion-ion interactions forms the most
stable interface. We also show that oxygen vacancies can be preferentially
stabilized across the interface via manipulating interfacial strain. We elucidate
that oxygen vacancies are most stable in the tensile-strain material, and
unstable in compressive strain material. This stability is explained from
equation-of-state analysis using a single crystal, where the oxygen vacancy shows
a larger volume than the oxygen ion, thus explaining its stability under tensile
strained conditions.
PMID- 25137405
TI - Label free detection of specific protein binding using a microwave sensor.
AB - The specific binding of streptavidin to biotinylated protein A was demonstrated
using a microwave detection system. In control experiments, the degree of non
specific binding was negligible. The method of detection was used to monitor the
adsorption of two other proteins, cytochrome c and glucose oxidase, on to the IDE
microwave sensor surface. The response of the sensor was also examined on
different substrate materials, with detection of protein binding observed
obtained on both smooth, conductive (gold) and on rough, insulating
(hydroxyapatite) surfaces.
PMID- 25137406
TI - R-134a (1,1,1,2-Tetrafluoroethane) Inhalation Induced Reactive Airways
Dysfunction Syndrome.
AB - R-134a (1,1,1,2-tetrafluoroethane) is widely used as a refrigerant and as an
aerosol propellant. Inhalation of R-134a can lead to asphyxia, transient
confusion, and cardiac arrhythmias. We report a case of reactive airways
dysfunction syndrome secondary to R-134a inhalation. A 60-year-old nonsmoking man
without a history of lung disease was exposed to an air conditioner refrigerant
spill while performing repairs beneath a school bus. Afterward, he experienced
worsening shortness of breath with minimal exertion, a productive cough, and
wheezing. He was also hypoxic. He was admitted to the hospital for further
evaluation. Spirometry showed airflow obstruction with an FEV1 1.97 L (45%
predicted). His respiratory status improved with bronchodilators and oral
steroids. A repeat spirometry 2 weeks later showed improvement with an FEV1 2.5 L
(60% predicted). Six months after the incident, his symptoms had improved, but he
was still having shortness of breath on exertion and occasional cough.
PMID- 25137407
TI - Polyhydroxybutyrate-coated magnetic nanoparticles for doxorubicin delivery:
cytotoxic effect against doxorubicin-resistant breast cancer cell line.
AB - In this study, polyhydroxybutyrate (PHB)-coated magnetic nanoparticles (MNPs)
were prepared by coprecipitation of iron salts (Fe and Fe) by ammonium hydroxide.
Characterizations of PHB-coated MNPs were performed by Fourier transform infrared
spectroscopy, x-ray diffraction, dynamic light scattering, thermal gravimetric
analysis, vibrating sample magnetometry, and transmission electron microscopy
analyses. Doxorubicin was loaded onto PHB-MNPs, and the release efficiencies at
different pHs were studied under in vitro conditions. The most efficient drug
loading concentration was found about 87% at room temperature in phosphate
buffered saline (pH 7.2). The drug-loaded MNPs were stable up to 2 months in
neutral pH for mimicking physiological conditions. The drug release studies were
performed with acetate buffer (pH 4.5) that mimics endosomal pH. Doxorubicin
(60%) released from PHB-MNPs within 65 hours. Doxorubicin-loaded PHB-MNPs were
about 2.5-fold more cytotoxic as compared with free drug on resistant Michigan
Cancer Foundation-7 (human breast adenocarcinoma, MCF-7) cell line (1 MUM
doxorubicin) in vitro. Therefore, doxorubicin-loaded PHB-MNPs lead to overcome
the drug resistance.
PMID- 25137408
TI - Nicotinic Acid and new-onset diabetes.
PMID- 25137409
TI - Maternal plasma DNA testing: experience of women counseled at a prenatal
diagnosis center.
AB - AIMS: To evaluate the early introduction of circulating cell-free (ccf) DNA
testing in a prenatal diagnosis center serving a statewide population. RESULTS: A
retrospective chart review of patients at high aneuploidy risk counseled during
the two 10-week periods that documents indication, risk, maternal age, insurance
coverage, decisions, and reasoning behind that decision. Among the 299 included
women, indication was advanced maternal age (17% with and 56% without an
additional indication), positive serum screen (15%), and abnormal ultrasound
(12%). Uptake increased from 10% to 17%, as did patient awareness of the test (4%
to 14%). Women with lower copayments were more likely to complete testing (23%
vs. 5%, p<0.001). Most women completing testing (75%) wanted to avoid an invasive
procedure, while those declining cited testing would not change anything (47%),
preferred diagnostic testing (16%), negative follow-up testing (20%), and
cost/insurance issues (9%). One of 42 tests was positive (trisomy 21).
CONCLUSIONS: Individual patient follow-up allows us to document ccfDNA-related
patient decision-making. Nearly half of the women did not want further testing
and one in seven preferred immediate diagnostic testing. Patient costs were a
barrier to testing that, if avoided, could increase test uptake by 50% or more.
PMID- 25137410
TI - AgONO-assisted direct C-H arylation of heteroarenes with anilines.
AB - A novel copper-catalyzed C-H arylation of heteroarenes with anilines by an in
situ diazonium reaction is established by using silver nitrite (AgONO) as an
unconventional nitrosating reagent under acid-free conditions. It provides a
complementary approach for the C-H arylation of electron-rich heteroarenes with
aromatic amines affording a variety of heterobiaryls in moderate to good yields.
PMID- 25137411
TI - Upregulated plasma and urinary levels of nucleosides as biological markers in the
diagnosis of primary gallbladder cancer.
AB - We first detected aberrant nucleoside levels in the plasma, urine, bile, and
tissues from cases and controls to explore them as biomarkers in the diagnosis of
gallbladder cancer. Reversed-phase high-performance liquid chromatography was
used to assess the levels of ten nucleosides in these samples from gallbladder
cancer patients, gallstone patients, and healthy controls. Plasma and urine
samples were collected from patients with gallbladder cancer (n = 202), patients
with gallstones (n = 203), and healthy controls (n = 205); bile and tissue
samples were collected from 91 gallbladder cancer patients, 93 gallstone
patients; and 90 were donated after cardiac death. Of the ten nucleosides
analyzed, eight urinary nucleosides, five plasma nucleosides, three bile
nucleosides, and one tissue nucleoside were significantly upregulated in the
gallbladder cancer patients compared to control groups (p < 0.05). Among these
upregulated nucleosides, the sensitivity, specificity, and accuracy of urinary
nucleosides in the diagnosis of gallbladder cancer patients were 89.4, 97.1, and
95.7%, respectively, those of plasma nucleosides were 91.2, 95.6, and 94.2%,
respectively, those of bile nucleosides were 95.3, 96.4, and 95.1%, respectively,
and those of tissue nucleosides were 86.2, 93.8, and 92.6%, respectively. These
results suggest that nucleosides may be as useful as biological markers for
gallbladder cancer.
PMID- 25137412
TI - Classification algorithms for the identification of structural injury in TBI
using brain electrical activity.
AB - BACKGROUND: There is an urgent need for objective criteria adjunctive to standard
clinical assessment of acute Traumatic Brain Injury (TBI). Details of the
development of a quantitative index to identify structural brain injury based on
brain electrical activity will be described. METHODS: Acute closed head injured
and normal patients (n=1470) were recruited from 16 US Emergency Departments and
evaluated using brain electrical activity (EEG) recorded from forehead
electrodes. Patients had high GCS (median=15), and most presented with low
suspicion of brain injury. Patients were divided into a CT positive (CT+) group
and a group with CT negative findings or where CT scans were not ordered
according to standard assessment (CT-/CT_NR). Three different classifier
methodologies, Ensemble Harmony, Least Absolute Shrinkage and Selection Operator
(LASSO), and Genetic Algorithm (GA), were utilized. RESULTS: Similar performance
accuracy was obtained for all three methodologies with an average
sensitivity/specificity of 97.5%/59.5%, area under the curves (AUC) of 0.90 and
average Negative Predictive Validity (NPV)>99%. Sensitivity was highest for CT+
cases with potentially life threatening hematomas, where two of three classifiers
were 100%. CONCLUSION: Similar performance of these classifiers suggests that the
optimal separation of the populations was obtained given the overlap of the
underlying distributions of features of brain activity. High sensitivity to CT+
injuries (highest in hematomas) and specificity significantly higher than that
obtained using ED guidelines for imaging, supports the enhanced clinical utility
of this technology and suggests the potential role in the objective, rapid and
more optimal triage of TBI patients.
PMID- 25137413
TI - Induction of highly functional hepatocytes from human umbilical cord mesenchymal
stem cells by HNF4alpha transduction.
AB - AIM: To investigate the differentiation potential of human umbilical mesenchymal
stem cells (HuMSCs) and the key factors that facilitate hepatic differentiation.
METHODS: HuMSCs were induced to become hepatocyte-like cells according to a
previously published protocol. The differentiation status of the hepatocyte-like
cells was examined by observing the morphological changes under an inverted
microscope and by immunofluorescence analysis. Hepatocyte nuclear factor 4 alpha
(HNF4alpha) overexpression was achieved by plasmid transfection of the hepatocyte
like cells. The expression of proteins and genes of interest was then examined by
Western blotting and reverse transcription-polymerase chain reaction (RT-PCR) or
real-time RT-PCR methods. RESULTS: Our results demonstrated that HuMSCs can
easily be induced into hepatocyte-like cells using a published differentiation
protocol. The overexpression of HNF4alpha in the induced HuMSCs significantly
enhanced the expression levels of hepatic-specific proteins and genes. HNF4alpha
overexpression may be associated with liver-enriched transcription factor
networks and the Wnt/beta-Catenin pathway. CONCLUSION: The overexpression of
HNF4alpha improves the hepatic differentiation of HuMSCs and is a simple way to
improve cellular sources for clinical applications.
PMID- 25137414
TI - Resting state functional connectivity of the anterior cingulate cortex in
veterans with and without post-traumatic stress disorder.
AB - Post-traumatic stress disorder (PTSD) is an anxiety disorder that is associated
with structural and functional alterations in several brain areas, including the
anterior cingulate cortex (ACC). Here, we examine resting state functional
connectivity of ACC subdivisions in PTSD, using a seed-based approach. Resting
state magnetic resonance images were obtained from male veterans with (n = 31)
and without (n = 25) PTSD, and healthy male civilian controls (n = 25). Veterans
with and without PTSD (combat controls) had reduced functional connectivity
compared to healthy controls between the caudal ACC and the precentral gyrus, and
between the perigenual ACC and the superior medial gyrus and middle temporal
gyrus. Combat controls had increased connectivity between the rostral ACC and
precentral/middle frontal gyrus compared to PTSD patients and healthy civilian
controls. The resting state functional connectivity differences in the perigenual
ACC network reported here indicate that veterans differ from healthy controls,
potentially due to military training, deployment, and/or trauma exposure. In
addition, specific alterations in the combat controls may potentially be related
to resilience. These results underline the importance of distinguishing trauma
exposed (combat) controls from healthy civilian controls when studying PTSD.
PMID- 25137415
TI - A nationwide 2010-2012 analysis of U.S. health care utilization in inflammatory
bowel diseases.
AB - BACKGROUND: Implementation of the 2010 Affordable Care Act (ACA) calls for a
collaborative effort to transform the U.S. health care system toward patient
centered and value-based care. To identify how specialty care can be improved, we
mapped current U.S. health care utilization in patients with inflammatory bowel
diseases (IBD) using a national insurance claims database. METHODS: We performed
a cross-sectional study analyzing U.S. health care utilization in 964,633
patients with IBD between 2010 and 2012 using insurance claims data, including
pharmacy and medical claims. Frequency of IBD-related care utilization
(medication, tests, and treatments) and their charges were evaluated.
Subsequently, outcomes were put into the framework of current U.S. guidelines to
identify areas of improvement. RESULTS: A disproportionate usage of
aminosalicylates in Crohn's disease (42%), frequent corticosteroid use (46%, with
9% long-term users), and low rates of corticosteroid-sparing drugs (thiopurines
15%; methotrexate 2.7%) were observed. Markers for inflammatory activity, such as
C-reactive protein or fecal calprotectin were not commonly used (8.8% and 0.13%,
respectively). Although infrequently used (11%), anti-TNF antibody therapy
represents a major part of observed IBD charges. CONCLUSIONS: This analysis shows
2010-2012 utilization and medication patterns of IBD health care in the United
States and suggests that improvement can be obtained through enhanced guidelines
adherence.
PMID- 25137416
TI - Disease course and management strategy of pouch neoplasia in patients with
underlying inflammatory bowel diseases.
AB - BACKGROUND: To evaluate the disease course and management strategy for pouch
neoplasia. METHODS: Patients undergoing ileal pouch surgery for underlying
ulcerative colitis who developed low-grade dysplasia (LGD), high-grade dysplasia,
or adenocarcinoma in the pouch were identified. RESULTS: All eligible 44 patients
were evaluated. Of the 22 patients with initial diagnosis of pouch LGD, 6 (27.3%)
had persistence or progression after a median follow-up of 9.5 (4.1-17.6) years.
Family history of colorectal cancer was shown to be a risk factor associated with
persistence or progression of LGD (P = 0.03). Of the 12 patients with pouch high
grade dysplasia, 5 (41.7%) had a history of (n = 2, 16.7%) or synchronous (n = 4,
33.3%) pouch LGD. Pouch high-grade dysplasia either persisted or progressed in 3
patients (25.0%) after the initial management, during a median time interval of
5.4 (2.2-9.2) years. Of the 14 patients with pouch adenocarcinoma, 12 (85.7%) had
a history of (n = 2, 14.3%) or synchronous dysplasia (n = 12, 85.7%). After a
median follow-up of 2.1 (0.6-5.2) years, 6 patients with pouch cancer (42.9%)
died. Comparison of patients with a final diagnosis of pouch adenocarcinoma (14,
32.6%), and those with dysplasia (29, 67.4%) showed that patients with
adenocarcinoma were older (P = 0.04) and had a longer duration from IBD diagnosis
or pouch construction to the detection of pouch neoplasia (P = 0.007 and P =
0.0013). CONCLUSIONS: The risk for progression of pouch dysplasia can be
stratified. The presence of family history of colorectal cancer seemed to
increase the risk for persistence or progression for patients with pouch LGD. The
prognosis for pouch adenocarcinoma was poor.
PMID- 25137417
TI - Barriers and facilitators to successful transition from pediatric to adult
inflammatory bowel disease care from the perspectives of providers.
AB - BACKGROUND: For adolescents and young adults (AYA) with inflammatory bowel
disease (IBD), the transition from pediatric to adult care is often challenging
and associated with gaps in care. Our study objectives were to (1) identify
outcomes for evaluating transition success and (2) elicit the major barriers and
facilitators of successful transition. METHODS: We interviewed pediatric and
adult IBD providers from across the United States with experience caring for AYAs
with IBD until thematic saturation was reached after 12 interviews. We elicited
the participants' backgrounds, examples of successful and unsuccessful transition
of AYAs for whom they cared, and recommendations for improving transition using
the Social-Ecological Model of Adolescent and Young Adult Readiness to Transition
framework. We coded interview transcripts using the constant comparative method
and identified major themes. RESULTS: Participants reported evaluating transition
success and failure using health care utilization outcomes (e.g., maintaining
continuity with adult providers), health outcomes (e.g., stable symptoms), and
quality of life outcomes (e.g., attending school). The patients' level of
developmental maturity (i.e., ownership of care) was the most prominent
determinant of transition outcomes. The style of parental involvement (i.e.,
helicopter parent versus optimally involved parent) and the degree of support by
providers (e.g., care coordination) also influenced outcomes. CONCLUSIONS: IBD
transition success is influenced by a complex interplay of patient developmental
maturity, parenting style, and provider support. Multidisciplinary IBD care teams
should aim to optimize these factors for each patient to increase the likelihood
of a smooth transfer to adult care.
PMID- 25137418
TI - Assessment of histologic disease activity in Crohn's disease: a systematic
review.
AB - BACKGROUND: Crohn's disease (CD) is an idiopathic, chronic, transmural
inflammatory disorder of the gastrointestinal tract. Because mucosal involvement
is near-universal, endoscopic healing has emerged as an important aspect in
improving outcome. However, resolution of histologic disease activity has
potential to convey additional benefit beyond that attained with endoscopic
healing alone. Validated scoring systems of histologic disease activity are
required to further assess this possibility. The aim of this study was to
systematically review the existing histologic disease activity indices (HDAI) for
CD and to assess their operating properties and potential use as outcome measures
in clinical trials. METHODS: MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane
Library (CENTRAL), and Digestive Disease Week (DDW) abstracts were searched from
1981 to April 2013 for applicable studies to identify relevant studies for review
and analysis. RESULTS: In total, 3732 citations were screened to obtain 89
articles for inclusion. Sixty-six HDAIs were characterized as either stepwise or
numerical instruments. These HDAIs were used for either assessment of response to
medical therapy or for comparison with biomarkers or imaging tests. None of the
HDAIs identified was developed according to currently accepted methods for
developing evaluative instruments, and none have been formally validated.
CONCLUSIONS: Measurement of histologic disease activity has potential value in
CD; however, no validated measures are available. Additional research is needed
to develop a methodologically rigorous instrument for use in clinical
investigation and potentially for clinical practice.
PMID- 25137421
TI - Serum androgen levels in elite female athletes.
AB - OBJECTIVE: Prior to the implementation of the blood steroidal module of the
Athlete Biological Passport, we measured the serum androgen levels among a large
population of high-level female athletes as well as the prevalence of biochemical
hyperandrogenism and some disorders of sex development (DSD). METHODS AND
RESULTS: In 849 elite female athletes, serum T, dehydroepiandrosterone sulphate,
androstenedione, SHBG, and gonadotrophins were measured by liquid chromatography
mass spectrometry high resolution or immunoassay. Free T was calculated. The
sampling hour, age, and type of athletic event only had a small influence on T
concentration, whereas ethnicity had not. Among the 85.5% that did not use oral
contraceptives, 168 of 717 athletes were oligo- or amenorrhoic. The oral
contraceptive users showed the lowest serum androgen and gonadotrophin and the
highest SHBG concentrations. After having removed five doped athletes and five
DSD women from our population, median T and free T values were close to those
reported in sedentary young women. The 99th percentile for T concentration was
calculated at 3.08 nmol/L, which is below the 10 nmol/L threshold used for
competition eligibility of hyperandrogenic women with normal androgen
sensitivity. Prevalence of hyperandrogenic 46 XY DSD in our athletic population
is approximately 7 per 1000, which is 140 times higher than expected in the
general population. CONCLUSION: This is the first study to establish normative
serum androgens values in elite female athletes, while taking into account the
possible influence of menstrual status, oral contraceptive use, type of athletic
event, and ethnicity. These findings should help to develop the blood steroidal
module of the Athlete Biological Passport and to refine more evidence-based fair
policies and recommendations concerning hyperandrogenism in female athletes.
PMID- 25137423
TI - Elevated FGF21 leads to attenuated postnatal linear growth in preterm infants
through GH resistance in chondrocytes.
AB - CONTEXT: The hormone fibroblast growth factor 21 (FGF21) is a key metabolic
regulator in the adaptation to fasting. In food-restricted mice, inhibition of
skeletal growth is mediated by the antagonistic effect of FGF21 on GH action in
the liver and growth plate. OBJECTIVE: The objective of the study was to assess
the role of FGF21 in growth regulation in humans using postnatal growth failure
of very preterm infants as a model. DESIGN: FGF21 levels were measured serially
in very preterm infants, and their linear growth evaluated from birth to term
equivalent age. Primary chondrocytes obtained from pediatric donors were used to
test whether FGF21 can directly interfere with GH signaling. RESULTS: A negative
association (beta -.415, P < .005, linear regression model) of FGF21 levels with
the change in SD score for length was found. In primary chondrocytes, FGF21
upregulated basal and GH-induced SOCS2 expression and inhibited GH-induced signal
transducer and activator of transcription 5 (STAT5) phosphorylation as well as GH
induced COLII and ALP expression. Finally, FGF21 inhibited GH-induced IGF-1
expression and cell proliferation, indicating GH resistance. However, FGF21 did
not affect IGF-1-induced cell proliferation. CONCLUSIONS: Elevated FGF21 serum
levels during the first weeks of life are independently associated with postnatal
growth failure in preterm infants. Furthermore, our data provide mechanistic
insights into GH resistance secondary to prematurity and may offer an explanation
for the growth failure commonly seen in chronic conditions of childhood.
PMID- 25137422
TI - Parathyroid hormone 1-84 alters circulating vascular endothelial growth factor
levels in hypoparathyroidism.
AB - CONTEXT: We previously reported on four patients treated with PTH(1-84) who
recovered from postoperative hypoparathyroidism many years after onset. Because
vascular endothelial growth factor (VEGF) has been shown to be necessary for the
induction of PTH-mediated angiogenesis, we postulated a possible role for VEGF in
the recovery of parathyroid function in these subjects. OBJECTIVE: Our objective
was to measure VEGF levels in subjects with hypoparathyroidism who regained
parathyroid gland function and matched controls. SETTING AND DESIGN: Subjects
with hypoparathyroidism who regained parathyroid gland function were each matched
to two hypoparathyroid controls by postoperative etiology, age (within 5 y),
menopausal status, and duration of hypoparathyroidism. We measured serum VEGF
levels at baseline and through 48 months of PTH(1-84) therapy. RESULTS: VEGF
levels increased after the initiation of PTH(1-84) therapy for the entire cohort,
from 309.7 +/- 162 pg/ml at baseline to 380.2 +/- 178 pg/ml at 12 months (P =
.03). Levels trended downward thereafter. There were no significant differences
in VEGF levels between the subjects with recovery of parathyroid function and the
matched controls. CONCLUSIONS: PTH(1-84) alters serum VEGF levels in subjects
with hypoparathyroidism. Additional investigation is necessary to understand the
mechanisms by which some subjects with postoperative hypoparathyroidism recover
parathyroid gland function.
PMID- 25137420
TI - Genetic risk score for prediction of newborn adiposity and large-for-gestational
age birth.
AB - CONTEXT: Macrosomic infants are at increased risk for adverse metabolic outcomes.
Improving prediction of large-for-gestational-age (LGA) birth may help prevent
these outcomes. OBJECTIVE: This study sought to determine whether genes
associated with obesity-related traits in adults are associated with newborn
size, and whether a genetic risk score (GRS) predicts LGA birth. SETTING AND
DESIGN: Single nucleotide polymorphisms (SNPs) in 40 regions associated with
adult obesity-related traits were tested for association with newborn size. GRS's
for birth weight and sum of skinfolds (SSF) specific to ancestry were calculated
using the most highly associated SNP for each ancestry in genomic regions with
one or more SNPs associated with birth weight and/or SSF in at least one ancestry
group or meta-analyses. PARTICIPANTS: Newborns from the Hyperglycemia Adverse
Pregnancy Outcomes Study were studied (942 Afro-Caribbean, 1294 Northern
European, 573 Mexican-American, and 1182 Thai). OUTCOME MEASURES: Birth weight
>90th percentile (LGA) and newborn SSF >90th percentile were primary outcomes.
RESULTS: After adjustment for ancestry, sex, gestational age at delivery, parity,
maternal genotype, maternal smoking/alcohol intake, age, body mass index, height,
blood pressure and glucose, 25 and 23 SNPs were associated (P < .001) with birth
weight and newborn SSF, respectively. The GRS was highly associated with both
phenotypes as continuous variables across all ancestries (P <= 1.6 * 10(-19)) and
improved prediction of birth weight and SSF >90th percentile when added to a
baseline model incorporating the covariates listed above. CONCLUSIONS: A GRS
comprised of SNPs associated with adult obesity-related traits may provide an
approach for predicting LGA birth and newborn adiposity beyond established risk
factors.
PMID- 25137424
TI - Intra-tissue steroid profiling indicates differential progesterone and
testosterone metabolism in the endometrium and endometriosis lesions.
AB - CONTEXT: Aberrant sex steroid signaling is suggested to promote endometriosis
growth by several mechanisms, and the tissue concentrations of sex steroids are
key determinants of the hormone action. However, their concentrations are only
superficially known in the endometrium and endometriosis lesions. OBJECTIVE: This
study sought to evaluate whether the tissue steroid hormone concentrations in
endometriosis differ from the endometrium or serum. MAIN OUTCOME MEASURES:
Steroid analysis of serum and tissue specimens of women with endometriosis (n =
60) and healthy controls (n=16) was measured, and supporting data from
quantitative RT-PCR for steroidogenic enzymes and explant cultures of a subset of
specimens is provided. RESULTS: Endometrial tissue progesterone (P4)
concentrations reflected the serum P4 levels during the menstrual cycle, whereas
in endometriosis lesions, the cycle-dependent change was missing. Remarkably high
tissue T concentrations were measured in endometriosis lesions independent of the
cycle phase, being 5-19 times higher than the corresponding serum levels.
Tissue/serum ratio of T was further increased in patients with contraceptive
medication. The altered tissue steroid concentrations in endometriosis were in
line with the expression of various steroidogenic enzymes in the lesions, of
which HSD3B2 showed constantly high expression, whereas CYP11A1 expression was
low. Furthermore, the high concentration of sex steroids detected in the ovarian
lesions involves their production by the lesion and by the adjacent ovarian
tissue. CONCLUSIONS: Endometriosis lesions present with progestin and androgen
metabolism, which are different from that of the endometrium, and the lesions are
characterized by high tissue T and a loss of cyclical changes in tissue P4
concentration.
PMID- 25137425
TI - No improvement of high-density lipoprotein (HDL) vasorelaxant effect despite
increase in HDL cholesterol concentration in type 2 diabetic patients treated
with glitazones.
AB - CONTEXT: High-density lipoproteins (HDLs) from type 2 diabetic patients are
unable to counteract the inhibitory effect of oxidized low-density lipoproteins
(ox-LDLs) on vasorelaxation. We hypothesized that glitazones, which improve
glycemic control and dyslipidemia, could correct this abnormality. OBJECTIVES AND
DESIGN: We compared the ability of HDL from controls (n = 12) and from type 2
diabetic patients before and after 6 months of treatment with either
rosiglitazone (n = 11) or pioglitazone (n = 8) to counteract the inhibitory
effect of ox-LDL on vasodilatation of rabbit aorta rings. RESULTS: Rosiglitazone
induced a decrease in hemoglobin A1c (7.7% +/- 1.1% vs 9.8% +/- 1.0%, P = .003)
and an increase in HDL cholesterol (1.14 +/- 0.32 vs 0.98 +/- 0.24 mmol/L, P =
.033). Pioglitazone induced a decrease in hemoglobin A1c (8.3% +/- 2.5% vs 9.5%
+/- 3.2%, P = .068) and serum triglycerides (1.58 +/- 0.89 vs 2.03 +/- 0.70
mmol/L, P = .069) and an increase in HDL cholesterol (1.39 +/- 0.22 vs 1.14 +/-
0.22 mmol/L, P = .018). The triglyceride content of HDL was unchanged by
rosiglitazone and was decreased by 25% (P = .068) by pioglitazone. HDL from
controls counteracted the inhibitory effect of ox-LDL on vasodilatation (maximal
relaxation [Emax] = 74.4% +/- 3.5% vs 51.9% +/- 3.3%, P = .0029), whereas HDL
from type 2 diabetic patients did not (Emax = 51.7% +/- 5.8% vs 52.3% +/- 4.6% [P
= .66] and 52.7% +/- 5.5% vs 51.9% +/- 4.5% [P = .78] for the rosiglitazone and
pioglitazone group, respectively). Rosiglitazone or pioglitazone did not improve
Emax (58.6% +/- 5.9% vs 52.3% +/- 4.6% [P = .15] and 49.3% +/- 6.5% vs 51.9% +/-
4.5% [P = .48], respectively). CONCLUSION: Glitazones increased the concentration
of HDL cholesterol without restoring the ability of HDL particles to protect the
endothelium from oxidative stress-induced dysfunction, meaning that HDL remained
dysfunctional with impaired antiatherogenic properties.
PMID- 25137426
TI - Comprehensive next-generation sequencing analyses of hypoparathyroidism:
identification of novel GCM2 mutations.
AB - CONTEXT: In most patients with hypoparathyroidism (HP), the etiology is not
defined clinically. Eight genes (AIRE, CASR, CLDN16, GATA3, GCM2, PTH, TBCE, and
TRPM6) are known to be responsible genes associated with HP; however, no previous
study has screened the eight responsible genes comprehensively in HP patients.
OBJECTIVES: This study was conducted to determine the genetic defect in HP
patients. We also described clinical and molecular findings of two HP patients
with novel GCM2 mutations. SUBJECTS AND METHODS: We enrolled 20 nonconsanguineous
Japanese patients with child-onset permanent HP without 22q11 deletion. Mutations
and genomic rearrangements involving the eight genes were screened by targeted
next-generation sequencing (NGS). We also screened genetic rearrangements by
array comparative genomic hybridization (aCGH) in the mutation-negative patients.
A putative deletion, which was suspected by NGS, was additionally analyzed by
droplet digital PCR (ddPCR) and junction PCR. Identified novel nucleotide-level
GCM2 mutants were characterized in vitro. RESULTS: We identified seven patients
with a single gene disorder, including a CASR mutation, GATA3 mutations, and
novel GCM2 mutations (R367Tfs*15, T370M, and the deletion encompassing exon 1).
This submicroscopic deletion, which had been suspected by NGS, could not be
detected by aCGH and was confirmed by ddPCR and junction PCR. Functional studies
of R367Tfs*- and T370M-GCM2 demonstrated a reduction of target gene
transactivation in both. CONCLUSIONS: Using comprehensive NGS analyses, we
identified the genetic defect in 35% of HP patients in our cohort and discovered
novel GCM2 mutations including submicroscopic deletion that was undetectable by
aCGH.
PMID- 25137429
TI - Impact factor for 2013.
PMID- 25137428
TI - Letrozole vs anastrozole for height augmentation in short pubertal males: first
year data.
AB - CONTEXT: Aromatase inhibitors are used off-label to treat short stature in
peripubertal boys. OBJECTIVE: To investigate short- and long-term hormonal and
auxologic differences in short pubertal boys treated with letrozole (L) or
anastrozole (A). DESIGN: PATIENTS are seen for laboratory evaluation and physical
examination every 6 months, bone age yearly, DEXA and spine film every 2 years.
They will be followed until they reach their final height. This is a preliminary
report after 1 year of treatment. SETTING: A single academic children's hospital
outpatient clinic. PATIENTS: Boys with age >10 years, bone age <= 14 years,
clinical and hormonal evidence of central puberty, and either height < fifth
percentile or predicted adult height (PAH) more than 10 cm below mid-parental
height (MPH). INTERVENTION: Letrozole (2.5 mg) or anastrozole (1 mg) was
administered orally each day. MAIN OUTCOME MEASURES: Hormonal and clinical
parameters, growth velocity, and change in bone age and PAH. RESULTS: Thirty-nine
boys have completed 1 year of treatment. Baseline means were age 14.1 years, PAH
166 cm, and testosterone 198 ng/dL. At 1 year, letrozole resulted in higher LH (L
6.1 +/- 2.5 vs A 3.2 +/- 1.7 IU/L) and testosterone (1038 +/- 348 vs 536 +/- 216
ng/dL) with lower estradiol (2.8 +/- 2.8 vs 5.6 +/- 2.9 pg/mL) and IGF-1 (237 +/-
51 vs 331 +/- 79 ng/mL). First year growth velocities were identical (7.2
cm/year), but an increase in PAH was greater in the anastrozole group (4.2 +/-
3.5 vs 1.4 +/- 4.4 cm, p = 0.03) after 1 year. CONCLUSIONS: We present first-year
data from a direct comparison of anastrozole and letrozole for height
augmentation in short pubertal boys. Letrozole was more potent in hormonal
manipulation than anastrozole. First-year growth velocities were comparable, but
improvement in PAH was greater in the anastrozole group. It remains to be seen if
positive PAH trends will translate to increase in final height in either group.
PMID- 25137427
TI - Prospective study of surgical treatment of acromegaly: effects on ghrelin,
weight, adiposity, and markers of CV risk.
AB - CONTEXT: Although epidemiological studies have found that GH and IGF-1
normalization reduce the excess mortality of active acromegaly to expected rates,
cross-sectional data report some cardiovascular (CV) risk markers to be less
favorable in remission than active acromegaly. OBJECTIVE: The objective of the
study was to test the hypothesis that remission of acromegaly after surgical
therapy increases weight and adiposity and some CV risk markers and these changes
are paralleled by a rise in ghrelin. DESIGN: Forty-two adults with untreated,
active acromegaly were studied prospectively. Changes in outcome measures from
before to after surgery were assessed in 26 subjects achieving remission (normal
IGF-1) and 16 with persistent active acromegaly (elevated IGF-1) after surgery.
SETTING: The study was conducted at tertiary referral centers for pituitary
tumors. MAIN OUTCOME MEASURES: Endocrine, metabolic, and CV risk parameters,
anthropometrics, and body composition by dual-energy X-ray absorptiometry were
measured. RESULTS: Remission increased total ghrelin, body weight, waist
circumference, C-reactive protein, homocysteine, high-density lipoprotein, and
leptin and reduced systolic blood pressure, homeostasis model assessment score,
triglycerides, and lipoprotein (a) by 6 months and for 32 +/- 4 months after
surgery. The ghrelin rise correlated with the fall in the levels of GH, IGF-1,
and insulin and insulin resistance. Weight, waist circumference, and ghrelin did
not increase significantly in the persistent active acromegaly group. Total body
fat, trunk fat, and perentage total body fat increased by 1 year after surgery in
15 remission subjects: the increase in body fat correlated with the rise in total
ghrelin. CONCLUSIONS: Although most markers of CV risk improve with acromegaly
remission after surgery, some markers and adiposity increase and are paralleled
by a rise in total ghrelin, suggesting that these changes may be related.
Understanding the mechanisms and long-term implications of the changes that
accompany treatment of acromegaly is important to optimizing management because
some aspects of the postoperative profile associate with the increased metabolic
and CV risk in other populations.
PMID- 25137430
TI - The effect of dexmedetomidine on intraocular pressure increase in patients during
robot-assisted laparoscopic radical prostatectomy in the steep Trendelenburg
position.
AB - PURPOSE: This study was to evaluate the effect of intraoperative continuous
infusion of dexmedetomidine on intraocular pressure (IOP) in patients undergoing
robot-assisted laparoscopic radical prostatectomy (RALRP) in the steep
Trendelenburg (ST). MATERIALS AND METHODS: Sixty-eight patients were randomly
divided into two groups. The dexmedetomidine group (Group D, n=34) received a
continuous infusion of dexmedetomidine at a rate of 0.4 MUg kg(-1) hour(-1) from
the induction of anesthesia until the end of the ST position, while the control
group (Group C, n=34) received an equal volume of physiologic saline at the same
rate under conventional general anesthesia with sevoflurane and remifentanil. IOP
was measured at 11 predefined time points for all patients. RESULTS: Significant
differences in IOP were detected between the two groups by a linear mixed model
analysis (p<0.001). The highest mean IOP was 19.9+/-5.0 mm Hg in Group D and
25.7+/-5.0 mm Hg in Group C; both were measured 60 minutes after the patients had
been placed in the ST position. No significant between-group differences in
ocular perfusion pressure, mean blood pressure, or heart rate were observed
between the two groups. No ocular or other complications were noted. CONCLUSION:
Intraoperative continuous infusion of dexmedetomidine may help alleviate IOP
increase in patients undergoing RALRP in the ST position.
PMID- 25137431
TI - Correction of the deviated septum: from ancient Egypt to the endoscopic era.
AB - BACKGROUND: Obstructed nasal breathing can occur due to deviation of the nasal
septum. When the external nose appears grossly normal and cosmesis is not the
focus, septoplasty has been the procedure used to straighten the septum with the
goal of improving nasal airflow. Septoplasty has evolved over time. METHODS: A
historical literature review was conducted to look for primary source journal
articles and medical conferences proccedings addressing the evolution of the
septoplasty procedure. RESULTS: Early techniques involved forcible fractures and
splinting. Submucous resection was the first major advancement in surgical
technique. Once the complications resulting from this technique were observed, it
was subsequently revised with attempts to better address the caudal septal
deviation. Attention was then turned to better incorporating the role surrounding
support structures, such as the upper lateral cartilages. The premaxilla-maxilla
approach attempted to address the overall nasal structure to best improve nasal
breathing. The advent of endoscopic technique has been the most recent shift in
surgical technique with improved visualization allowing for targeted septoplasty
and reoperation on complicated cases including pituitary and skull base surgery.
CONCLUSION: This paper discusses the evolution of septoplasty techniques over
time from the initial undertakings of the ancient Egyptians to the modern-day
septoplasty. While the principles behind septoplasty have remained much the same,
experience has allowed for refinement of surgical technique. No doubt new
instrumentations and innovations will further help to tailor the practice of
septoplasty to the anatomy and functional needs of each individual patient.
PMID- 25137433
TI - Enhanced electrochemical methanation of carbon dioxide with a dispersible
nanoscale copper catalyst.
AB - Although the vast majority of hydrocarbon fuels and products are presently
derived from petroleum, there is much interest in the development of routes for
synthesizing these same products by hydrogenating CO2. The simplest hydrocarbon
target is methane, which can utilize existing infrastructure for natural gas
storage, distribution, and consumption. Electrochemical methods for methanizing
CO2 currently suffer from a combination of low activities and poor selectivities.
We demonstrate that copper nanoparticles supported on glassy carbon (n-Cu/C)
achieve up to 4 times greater methanation current densities compared to high
purity copper foil electrodes. The n-Cu/C electrocatalyst also exhibits an
average Faradaic efficiency for methanation of 80% during extended electrolysis,
the highest Faradaic efficiency for room-temperature methanation reported to
date. We find that the level of copper catalyst loading on the glassy carbon
support has an enormous impact on the morphology of the copper under catalytic
conditions and the resulting Faradaic efficiency for methane. The improved
activity and Faradaic efficiency for methanation involves a mechanism that is
distinct from what is generally thought to occur on copper foils. Electrochemical
data indicate that the early steps of methanation on n-Cu/C involve a pre
equilibrium one-electron transfer to CO2 to form an adsorbed radical, followed by
a rate-limiting non-electrochemical step in which the adsorbed CO2 radical reacts
with a second CO2 molecule from solution. These nanoscale copper electrocatalysts
represent a first step toward the preparation of practical methanation catalysts
that can be incorporated into membrane-electrode assemblies in electrolyzers.
PMID- 25137434
TI - Development of nanodroplets for histotripsy-mediated cell ablation.
AB - This report describes the synthesis of amphiphilic copolymers (ABC-1 and ABC-2)
composed of a hydrophilic poly(ethylene glycol) (PEG) block, a central
poly(acrylic acid) (PAA) block, and a random copolymer of heptadecafluorodecyl
methacrylate (HDFMA) and methyl methacrylate (MMA) forming the hydrophobic block,
which are used to form nanodroplets for ultrasound-mediated cell ablation.
Specifically, the effect of molecular weight of PEG and P(HDFMA-co-MMA) blocks on
polymer's ability to self-assemble around a variable amount (0%, 1%, and 2% v/v)
of perfluoropentane (PFP) forming nanodroplets is investigated. The ability of
different nanodroplets formulations embedded with a monolayer of red blood cells
(RBCs) in tissue-mimicking agarose phantoms to initiate and sustain a bubble
cloud in response to ultrasound treatments with different acoustic pressures and
the associated ablation of RBCs were also investigated. Results show that ABC-1
polymer composed of a 2 kDa PEG block and a 6.7 kDa P(HDFMA-co-MMA) block better
encapsulate the PFP core compared to ABC-2 polymer composed of a 5 kDa PEG block
and 11.4 kDa P(HDFMA-co-MMA) block. Further, the ablative capacity indicated by
the damage area in the RBCs monolayer increased with the increase in PFP content
and reached its maximum with the nanodroplets formulated using ABC-1 polymer and
encapsulating 2% v/v PFP. The nanodroplets formulated using ABC-1 polymer and
loaded with 2% PFP produced the cavitation cloud and exhibited their ablative
effect at an acoustic pressure that is 2.5-fold lower than the acoustic pressure
needed to generate the same effect using a histotripsy (ultrasound) pulse alone,
which indicates the ability of these nanodroplets to achieve targeted and self
limiting fractionation of disease cells while sparing neighboring healthy ones.
Results also show that effective nanodroplets maintained their size and
concentration upon incubation with bovine serum albumin at 37 degrees C for 24
h, which indicates their stability in physiologic conditions and their promise
for in vivo cancer cell ablation.
PMID- 25137437
TI - Understanding solvation in the low global warming hydrofluoroolefin HFO-1234ze
propellant.
AB - Hydrofluoroolefins (HFOs), with zero ozone-depleting effect and very low global
warming potential, are considered to be the next-generation high-pressure working
fluids. They have industrial relevance in areas including refrigeration and
medical aerosols. One major challenge expected in the replacement of existing
working fluids with HFOs is the solubility and solvation of additives in such
hydrophobic and oleophobic low dielectric semifluorinated solvents. The study of
the solvation of chemistries that represent those additives by HFOs is,
therefore, of great relevance. In this work, we systematically investigate how
the polarity and structure of fragments (the tail, t) that represent those
additives affect their binding energy (Eb) with HFO-1234ze (1,1,1,3
tetrafluoropropene) (the solvent, s; Eb(st)). We also compare and contrast those
results with those for the working fluids that are most widely used in the
industry, the hydrofluoroalkanes (HFAs) HFA-134a and HFA-227. Three main
chemistries were investigated: alkanes, ethers, and esters. It was found that HFO
1234ze interacts quite favorably with ethers and esters, as indicated by their
Eb(st), while Eb(st) with alkanes was much lower. While ether and ester groups
showed little difference in Eb(st), the much lower self-interaction energy
between ether tail-tail fragments (Eb(tt)) is expected to result in improved
solubility/solvation of those groups in HFO-1234ze when compared with the more
polar ester groups. The ratio Eb(st)/Eb(tt) is defined as the enhancement factor
(Eenh) and is expected to be a better predictor of solubility/solvation of the
tail fragments. The branching of the tail groups upon the addition of pendant CH3
groups did not significantly affect the solvation by the propellant. At low
branching density (one CH3 pendant group), it did not affect tail-tail self
interaction either. However, at high enough branching (two CH3 groups), steric
hindrance caused a significant decrease in Eb(tt) and thus an increase in Eenh,
suggesting that branching may be used as a strategy to enhance solvation in HFO
propellants. Finally, the solvation behavior of HFO-1234ze was found to be
similar to that of HFA-134a, thus suggesting similar considerations may apply for
both propellants, when solvation properties are of a concern to the application.
PMID- 25137438
TI - Triethylborane-initiated radical chain fluorination: a synthetic method derived
from mechanistic insight.
AB - We offer a mild, metal-free sp(3) C-H fluorination alternative using Selectfluor
and a substoichiometric amount of triethylborane--an established radical
initiator in the presence of O2. This radical-chain-based synthetic method is
particularly noteworthy as an offspring of the insight gained from a mechanistic
study of copper-promoted aliphatic fluorination, constructively turning O2 from
an enemy to an ally. Furthermore, BEt3/O2 is a preferred initiator in industrial
processes, as it is economical, is low in toxicity, and lends way to easier
workup.
PMID- 25137436
TI - Effects of nanopillar array diameter and spacing on cancer cell capture and cell
behaviors.
AB - While substrates with nanopillars (NPs) have emerged as promising platforms for
isolation of circulating tumor cells (CTCs), the influence of diameter and
spacing of NPs on CTC capture is still unclear. In this paper, CTC-capture yield
and cell behaviors have been investigated by using antibody functionalized NPs of
various diameters (120-1100 nm) and spacings (35-800 nm). The results show a
linear relationship between the cell capture yield and effective contact area of
NP substrates where a NP array of small diameter and reasonable spacing is
preferred; however, spacing that is too small or too large adversely impairs the
capture efficiency and specificity, respectively. In addition, the formation of
pseudopodia between captured cells and the substrate is found to be dependent not
only on cell adhesion status but also on elution strength and shear direction.
These findings provide essential guidance in designing NP substrates for more
efficient capture of CTCs and manipulation of cytomorphology in future.
PMID- 25137435
TI - Evidence that the C-terminal domain of a type B PutA protein contributes to
aldehyde dehydrogenase activity and substrate channeling.
AB - Proline utilization A (PutA) is a bifunctional enzyme that catalyzes the
oxidation of proline to glutamate. Structures of type A PutAs have revealed the
catalytic core consisting of proline dehydrogenase (PRODH) and Delta(1)-pyrroline
5-carboxylate dehydrogenase (P5CDH) modules connected by a substrate-channeling
tunnel. Type B PutAs also have a C-terminal domain of unknown function (CTDUF)
that is absent in type A PutAs. Small-angle X-ray scattering (SAXS), mutagenesis,
and kinetics are used to determine the contributions of this domain to PutA
structure and function. The 1127-residue Rhodobacter capsulatus PutA (RcPutA) is
used as a representative CTDUF-containing type B PutA. The reaction progress
curve for the coupled PRODH-P5CDH activity of RcPutA does not exhibit a time lag,
implying a substrate channeling mechanism. RcPutA is monomeric in solution, which
is unprecedented for PutAs. SAXS rigid body modeling with target-decoy validation
is used to build a model of RcPutA. On the basis of homology to aldehyde
dehydrogenases (ALDHs), the CTDUF is predicted to consist of a beta-hairpin fused
to a noncatalytic Rossmann fold domain. The predicted tertiary structural
interactions of the CTDUF resemble the quaternary structural interactions in the
type A PutA dimer interface. The model is tested by mutagenesis of the
dimerization hairpin of a type A PutA and the CTDUF hairpin of RcPutA. Similar
functional phenotypes are observed in the two sets of variants, supporting the
hypothesis that the CTDUF mimics the type A PutA dimer interface. These results
suggest annotation of the CTDUF as an ALDH superfamily domain that facilitates
P5CDH activity and substrate channeling by stabilizing the aldehyde-binding site
and sealing the substrate-channeling tunnel from the bulk medium.
PMID- 25137439
TI - Fabrication of Si/ZnS radial nanowire heterojunction arrays for white light
emitting devices on Si substrates.
AB - Well-separated Si/ZnS radial nanowire heterojunction-based light-emitting devices
have been fabricated on large-area substrates by depositing n-ZnS film on p-type
nanoporous Si nanowire templates. Vertically oriented porous Si nanowires on p-Si
substrates have been grown by metal-assisted chemical etching catalyzed using Au
nanoparticles. Isolated Si nanowires with needle-shaped arrays have been made by
KOH treatment before ZnS deposition. Electrically driven efficient white light
emission from radial heterojunction arrays has been achieved under a low forward
bias condition. The observed white light emission is attributed to blue and green
emission from the defect-related radiative transition of ZnS and Si/ZnS
interface, respectively, while the red arises from the porous surface of the Si
nanowire core. The observed white light emission from the Si/ZnS nanowire
heterojunction could open up the new possibility to integrate Si-based optical
sources on a large scale.
PMID- 25137440
TI - A simple validated RP-HPLC bioanalytical method for the quantitative
determination of a novel valproic acid arylamide derivative in rat hepatic
microsomes.
AB - A simple and specific bioanalytical method based on reversed-phase high
performance liquid chromatography (RP-HPLC) coupled with ultraviolet detection
was developed and validated for the determination of a novel valproic acid
arylamide, N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) in rat hepatic
microsomes (a subcellular fraction containing phase I enzymes, especially
cytochrome P450). The chromatographic separation was achieved using a reversed
phase Zorbax SB-C18 column and a mobile phase of acetic acid in water (0.2% v/v)
and acetonitrile (40:60 v/v) with a flow rate of 0.5 mL/min. The calibration
curve was linear over the range of 882-7060 ng/mL (r(2) = 0.9987), and the lower
limit of quantification and the lower limit of determination were found to be 882
and 127.99 ng/mL, respectively. The method was validated with excellent
sensitivity, and intra-day accuracy and precision varied from 93.79 to 93.12%,
and from 2.12 to 4.36%, respectively. The inter-day accuracy and precision ranged
from 93.29 to 97.30% and from 0.68 to 3.60%, respectively. The recovery of HO
AAVPA was measured between 91.36 and 97.98%. The assay was successfully applied
to the analysis of kinetic metabolism and pharmacokinetic parameters in vitro by
a substrate depletion approach.
PMID- 25137441
TI - Syntheses of two vanadium oxide-fluoride materials that differ in phase
matchability.
AB - The syntheses of two noncentrosymmetric (NCS) vanadium oxide-fluoride compounds
that originate from the same synthetic reagent concentrations are presented.
Hydrothermal and low-temperature syntheses allow the isolation of metastable
products that may form new phases (or decompose) upon heating and allow creation
of chemically similar but structurally different materials. NCS materials
synthesis has been a long-standing goal in inorganic chemistry: in this article,
we compare two chemically similar NCS inorganic materials, NaVOF(4)(H(2)O) (I)
and NaVO(2-x)F(2+x) (II; x = 1/3). These materials originate from the same,
identical reagent mixtures but are synthesized at different temperatures: 100
degrees C and 150 degrees C, respectively. Compound I crystallizes in Pna2(1): a
= 9.9595(4) A, b = 9.4423(3) A, and c = 4.8186(2) A. Compound II crystallizes in
P2(1): a = 6.3742(3) A, b = 3.5963(2) A, c = 14.3641(7) A, and beta = 110.787(3)
degrees . Both materials display second-harmonic-generation activity; however,
compound I is type 1 non-phase-matchable, whereas compound II is type 1 phase
matchable.
PMID- 25137442
TI - Bioarcheology has a "health" problem: conceptualizing "stress" and "health" in
bioarcheological research.
AB - This article provides a critical historical overview of the stress concept in
bioarcheological research and critically evaluates the term "health" in reference
to skeletal samples. Stress has a considerable history in 20th century
physiological research, and the term has reached a critical capacity of meaning.
Stress was operationalized around a series of generalized physiological responses
that were associated with a deviation from homeostasis. The term was incorporated
into anthropological research during the mid-20th century, and further defined in
bioarcheological context around a series of skeletal indicators of physiological
disruption and disease. Emphases on stress became a predominate area of research
in bioarcheology, and eventually, many studies utilized the terms "health" and
"stress" interchangeably as part of a broader, problem-oriented approach to
evaluating prehistoric population dynamics. Use of the term "health" in relation
to skeletal samples is associated with the intellectual history of
bioarcheological research, specifically influences from cultural ecology and
processualist archeology and remains problematic for two reasons. First, health
represents a comprehensive state of well-being that includes physiological status
and individual perception, factors that cannot be readily observed in skeletal
samples. Second, the categorization of populations into relative levels of health
represents a typological approach, however unintentional. This article advocates
for the integration of methodological and theoretical advances from human biology
and primatology, while simultaneously incorporating the theoretical constructs
associated with social epidemiology into bioarcheological research. Such an
approach will significantly increase the applicability of bioarcheological
findings to anthropological and evolutionary research, and help realize the goal
of a truly relevant bioarcheological paradigm.
PMID- 25137443
TI - Importance of sample form and surface temperature for analysis by ambient plasma
mass spectrometry (PADI).
AB - Many different types of samples have been analyzed in the literature using plasma
based ambient mass spectrometry sources; however, comprehensive studies of the
important parameters for analysis are only just beginning. Here, we investigate
the effect of the sample form and surface temperature on the signal intensities
in plasma-assisted desorption ionization (PADI). The form of the sample is very
important, with powders of all volatilities effectively analyzed. However, for
the analysis of thin films at room temperature and using a low plasma power, a
vapor pressure of greater than 10(-4) Pa is required to achieve a sufficiently
good quality spectrum. Using thermal desorption, we are able to increase the
signal intensity of less volatile materials with vapor pressures less than 10(-4)
Pa, in thin film form, by between 4 and 7 orders of magnitude. This is achieved
by increasing the temperature of the sample up to a maximum of 200 degrees C.
Thermal desorption can also increase the signal intensity for the analysis of
powders.
PMID- 25137444
TI - Best practice or last resort? Employing graduate teaching assistants as clinical
instructors.
AB - Many institutions need to employ GTAs, and students need the teaching experience
that working as a GTA offers. Some recommendations to support a positive outcome
are as follows: (1) GTAs should not make up a significantly large percentage of
the total clinical faculty employed. Yet within reasonable limits, employ GTAs,
wherever possible; (2) evaluate GTAs' performance on an ongoing as well as
summative basis to be sure that they are meeting expectations set for providing
instruction; and (3) hire new faculty members who worked previously as a GTA or
in similar roles to ensure faculty succession with educators who are clinical
experts.
PMID- 25137445
TI - Use of multiuser, high-fidelity virtual simulation to teach leadership styles to
nursing students.
PMID- 25137446
TI - Integrating an academic electronic health record in a nursing program: creating a
sense of urgency and sustaining change.
PMID- 25137447
TI - Clinical coordinator role in a nursing program: challenges and rewards, perils
and pitfalls.
PMID- 25137448
TI - Interprofessional education competencies.
PMID- 25137449
TI - Barcode training innovation.
PMID- 25137450
TI - Podcasting in undergraduate nursing programs.
AB - Little information is available regarding the value of podcasting in nursing
education. This mixed-methods study described nursing students' (n=101)
perceptions of podcasted materials, the benefits of podcasting, and when and
where students used podcasted materials. Students (86%) believed podcasts
enriched their learning, and 95% reported podcasts as valuable tools in the
learning environment. Most students (94%) would recommend podcasting in other
courses and accessed podcast materials 3 times per week. More than half of the
students (55%) accessed podcast materials in multiple places (ie, in the car, in
the home, and at school).
PMID- 25137451
TI - Investigating the effects of solvent on the ultrafast dynamics of a
photoreversible ruthenium sulfoxide complex.
AB - The photochromic complex [Ru(bpy)2(pySO)](2+) [pySO is 2
(isopropylsulfinylmethyl)pyridine] undergoes wavelength specific, photoreversible
S -> O and O -> S linkage isomerizations. Irradiation of the ground state S
bonded complex with blue light produces the O-bonded isomer, while irradiation of
the O-bonded isomer with green light produces the S-bonded isomer. Furthermore,
isomerization time constants are solvent-dependent. Ultrafast transient
absorption spectroscopy has been employed to investigate the relaxation processes
that lead to S -> O isomerization in 1,2-dichloroethane, propylene carbonate, and
ethylene glycol. The isomerization is most rapid in 1,2-dichloroethane and
slowest in ethylene glycol. Photochemical reversion of the O-bonded isomer in
propylene carbonate has further been investigated and indicates similar
relaxation or isomerization kinetics, though the excited states that lead to
isomerization are distinct between the S- and O-bonded isomers.
PMID- 25137452
TI - A primer on TCR signaling.
PMID- 25137453
TI - Integrative biology of T cell activation.
AB - The activation of T cells mediated by the T cell antigen receptor (TCR) requires
the interaction of dozens of proteins, and its malfunction has pathological
consequences. Our major focus is on new developments in the systems-level
understanding of the TCR signal-transduction network. To make sense of the
formidable complexity of this network, we argue that 'fine-grained' methods are
needed to assess the relationships among a few components that interact on a
nanometric scale, and those should be integrated with high-throughput '-omic'
approaches that simultaneously capture large numbers of parameters. We illustrate
the utility of this integrative approach with the transmembrane signaling protein
Lat, which is a key signaling hub of the TCR signal-transduction network, as a
connecting thread.
PMID- 25137454
TI - Insights into the initiation of TCR signaling.
AB - The initiation of T cell antigen receptor signaling is a key step that can result
in T cell activation and the orchestration of an adaptive immune response. Early
events in T cell receptor signaling can distinguish between agonist and
endogenous ligands with exquisite selectivity, and show extraordinary sensitivity
to minute numbers of agonists in a sea of endogenous ligands. We review our
current knowledge of models and crucial molecules that aim to provide a
mechanistic explanation for these observations. Building on current understanding
and a discussion of unresolved issues, we propose a molecular model for
initiation of T cell receptor signaling that may serve as a useful guide for
future studies.
PMID- 25137463
TI - Francois Kourilsky 1934-2014.
PMID- 25137455
TI - Serine-threonine kinases in TCR signaling.
AB - T lymphocyte proliferation and differentiation are controlled by signaling
pathways initiated by the T cell antigen receptor. Here we explore how key serine
threonine kinases and their substrates mediate T cell signaling and coordinate T
cell metabolism to meet the metabolic demands of participating in an immune
response.
PMID- 25137456
TI - The self-obsession of T cells: how TCR signaling thresholds affect fate
'decisions' and effector function.
AB - Self-reactivity was once seen as a potential characteristic of T cells that was
eliminated by clonal selection to protect the host from autoimmune pathology. It
is now understood that the T cell repertoire is in fact broadly self-reactive,
even self-centered. The strength with which a T cell reacts to self ligands and
the environmental context in which this reaction occurs influence almost every
aspect of T cell biology, from development to differentiation to effector
function. Here we highlight recent advances and discoveries that relate to T cell
self-reactivity, with a particular emphasis on T cell antigen receptor (TCR)
signaling thresholds.
PMID- 25137464
TI - Breaking barriers: a GPCR triggers immunity in nematodes.
PMID- 25137465
TI - c-Myc and AP4: a relay team for metabolic reprogramming of CD8+ T cells.
PMID- 25137474
TI - Retraction: Interleukin 17 acts in synergy with B cell-activating factor to
influence B cell biology and the pathophysiology of systemic lupus erythematosus.
PMID- 25137466
TI - RNA exosomes keep endogenous RNA under the radar.
PMID- 25137478
TI - Small-molecule suppression of beta-lactam resistance in multidrug-resistant gram
negative pathogens.
AB - Recent efforts toward combating antibiotic resistance in bacteria have focused on
Gram-positive bacteria; however, multidrug-resistant Gram-negative bacteria pose
a significant risk to public health. An orthogonal approach to the development of
new antibiotics is to develop adjuvant compounds that enhance the susceptibility
of drug-resistant strains of bacteria to currently approved antibiotics. This
paper describes the synthesis and biological activity of a library of aryl amide
2-aminoimidazoles based on a lead structure from an initial screen. A small
molecule was identified from this library that is capable of lowering the minimum
inhibitory concentration of beta-lactam antibiotics by up to 64-fold.
PMID- 25137479
TI - High-density, stretchable, all-solid-state microsupercapacitor arrays.
AB - We report on the successful fabrication of stretchable microsupercapacitor (MSC)
arrays on a deformable polymer substrate that exhibits high electrochemical
performance even under mechanical deformation such as bending, twisting, and
uniaxial strain of up to 40%. We designed the deformable substrate to minimize
the strain on MSCs by adopting a heterogeneous structure consisting of stiff PDMS
islands (on which MSCs are attached) and a soft thin film (mixture of Ecoflex and
PDMS) between neighboring PDMS islands. Finite element method analysis of strain
distribution showed that an almost negligible strain of 0.47% existed on the PDMS
islands but a concentrated strain of 107% was present on the soft thin film area
under a uniaxial strain of 40%. The use of an embedded interconnection of the
liquid metal Galinstan helped simplify the fabrication and provided mechanical
stability under deformation. Furthermore, double-sided integration of MSCs
increased the capacitance to twice that of MSCs on a conventional planar
deformable substrate. In this study, planar-type MSCs with layer-by-layer
assembled hybrid thin film electrodes of MWNT/Mn3O4 and PVA-H3PO4 electrolyte
were fabricated; when they are integrated into a circuit, these MSCs increase the
output voltage beyond the potential of the electrolyte used. Therefore, various
LEDs that require high voltages can be operated under a high uniaxial strain of
40% without any decrease in their brightness. The results obtained in this study
demonstrate the high potential of our stretchable MSC arrays for their
application as embedded stretchable energy storage devices in bioimplantable and
future wearable nanoelectronics.
PMID- 25137480
TI - Microgel-like aggregates of isotactic and atactic poly(methacrylic acid) chains
in aqueous alkali chloride solutions as evidenced by light scattering.
AB - A comparative light-scattering study of isotactic and atactic poly(methacrylic
acid), iPMA and aPMA, respectively, in aqueous solutions with added alkali
chlorides, XCl (X = Li, Na, Cs), at 25 degrees C and XCl concentration of 0.1
mol L(-1), demonstrates that both PMA isomers are strongly associated at low
degrees of neutralization, alphaN (= 0 for aPMA and 0.25 for iPMA), in the
presence of all XCls. The shape parameter rho and the scattering functions
suggest that aggregates have the characteristics of microgel particles, with a
dense core surrounded by a less dense shell. The extent of aggregation depends on
the stereoregular structure of the polymer and on the type of the added cation.
Li(+) and Na(+) ions support aggregation better than Cs(+) ions. Besides, iPMA
chains are more strongly aggregated than aPMA chains and form particles with a
denser core. A model of the aggregation process is suggested for iPMA. At high
alphaN, a slow diffusive process (so-called extraordinary or anomalous mode in
diffusion of polyelectrolytes), arising from electrostatic interactions between
charged chains, is observed for both PMAs. Results suggest that under the same
experimental conditions iPMA is effectively more charged than aPMA. The role of
ions in the slow-mode phenomenon is less pronounced than in aggregation.
PMID- 25137481
TI - Response to "power in the study of mortality and necrotizing soft tissue
infections".
PMID- 25137482
TI - Resurfaced shape complementary proteins that selectively bind the oncoprotein
gankyrin.
AB - Increased cellular levels of protein-protein interactions involving the ankyrin
repeat oncoprotein gankyrin are directly linked to aberrant cellular events and
numerous cancers. Inhibition of these protein-protein interactions is thus an
attractive therapeutic strategy. However, the relatively featureless topology of
gankyrin's putative binding face and large surface areas involved in gankyrin
dependent protein-protein interactions present a dramatic challenge to small
molecule discovery. The size, high folding energies, and well-defined surfaces
present in many proteins overcome some of the challenges faced by small molecule
discovery. We used split-superpositive Green Fluorescent Protein (split-spGFP)
reassembly to screen a 5*10(9) library of resurfaced proteins that are shape
complementary to the putative binding face of gankyrin and identified mutants
that potently and selectively bind this oncoprotein in vitro and in living cells.
Collectively, our findings represent the first synthetic proteins that bind
gankyrin and may represent a general strategy for developing protein basic
research tools and drug leads that bind disease-relevant ankyrin repeats.
PMID- 25137483
TI - Carbohydrate-to-carbohydrate interactions between alpha2,3-linked sialic acids on
alpha2 integrin subunits and asialo-GM1 underlie the bone metastatic behaviour of
LNCAP-derivative C4-2B prostate cancer cells.
AB - Complex interplays among proteins, lipids and carbohydrates can alter the
phenotype and are suggested to have a crucial role in tumour metastasis. Our
previous studies indicated that a complex of the GSLs (glycosphingolipids), AsGM1
(asialo-GM1), which lacks alpha2,3-linked sialic acid, and alpha2beta1 integrin
receptors is responsible for the metastatic behaviour of C4-2B prostate cancer
cells. Herein, we identified and addressed the functional significance of changes
in sialylation during prostate cancer progression. We observed an increase in
alpha2,3-linked sialic acid residues on alpha2 subunits of alpha2beta1 integrin
receptors, correlating with increased gene expression of alpha2,3-STs
(sialyltransferases), particularly ST3GAL3. Cell surface alpha2,3-sialylation of
alpha2 subunits was required for the integrin alpha2beta1-dependent cell adhesion
to collagen type I and the same alpha2,3-linked sialic acid residues on the
integrin receptor were responsible for the interaction with the carbohydrate
moiety of AsGM1, explaining the complex formation between AsGM1 and alpha2beta1
integrin receptors. These results provide novel insights into the role of sialic
acids in the organization and function of important membrane components in
invasion and metastatic processes.
PMID- 25137484
TI - Variability and reliability of diurnal cortisol in younger and older adults:
implications for design decisions.
AB - The extant research is inconclusive regarding the best sampling methods to
construct reliable measures of between-person differences in derived parameters
of diurnal cortisol, and no study provides such recommendations for detecting
within-person changes. These studies determined how many days of sampling are
necessary to assess between-person differences and within-person changes over
multiple occasions in diurnal mean, diurnal slope, and area under the curve
(AUC). Generalizability and decision analyses were conducted on diurnal salivary
cortisol data from two separate longitudinal studies, one with younger adults
(N=124) and one with older adults (N=148). In both studies, results indicated
that 3 days of data collection provided the minimal level of reliability in mean
cortisol to detect between-person differences; 4-8 days were necessary to
reliably assess AUC, and 10 days for cortisol slope. Similarly, in order to
reliably characterize within-person changes across occasions, at least 3 days of
data collection were needed for mean cortisol and AUC and 5-8 days for slope.
Results also indicated that only two samples per day, taken morning and evening,
could faithfully reproduce the diurnal slope calculated from 3 or 4 samples
(r=.97-.99). Instead of having participants provide many samples per day over the
course of a few days, we recommend collecting fewer samples per day over more
days.
PMID- 25137486
TI - Staffing of healthcare workers and patient mortality: randomized trials needed.
AB - In a Perspective accompanying a study by Benjamin Bray and colleagues, Meeta
Kerlin discusses the evidence that physician and nurse workforces are associated
with patient mortality, why clearer guidelines for appropriate workforce size are
not available, and the next steps needed to address the knowledge gaps. Please
see later in the article for the Editors' Summary.
PMID- 25137485
TI - Stability and predictors of change in salivary cortisol measures over six years:
MESA.
AB - A major challenge in characterizing features of the daily cortisol curve is
variability in features over time. Few studies have examined the stability of
daily features of the cortisol curve over long periods or the predictors of long
term changes. Repeated salivary cortisol measures on 580 adults from the MESA
Stress study were used to examine the stability of various features of the daily
cortisol curve (wakeup value, the cortisol awakening response (CAR), the early
and late decline slope and the area under the curve (AUC)), over short periods
(several days) and long periods (approximately 6-years) and to investigate the
association of demographic factors with the changes. Intraclass correlation
coefficients (ICCs) were used to estimate the short and long term stability.
Piecewise linear mixed models were used to assess factors associated with changes
in features over time. For most features, short term stability (ICCs: 0.17-0.74)
was higher than long term stability (ICCs: 0.05-0.42), and long term stability
was highest when several days were averaged for each time point. The decline over
the day showed the highest long term stability: when several days for each wave
were averaged the stability of the daily decline slope across 6 years was similar
(or higher) than the stability across short periods. AUC had high stability over
short periods (ICCs: 0.65-0.74) but much lower stability across long periods
(ICC: 0.05). All features of daily cortisol curve investigated changed
significantly over the approximately 6 year follow-up period. The wakeup cortisol
became higher; the CAR became smaller; both the early and late decline became
flatter; and the AUC became larger. Hispanics experienced significantly larger
increases in the wakeup value; and African-Americans and Hispanics showed less
flattening over time of the early decline slope than Non-Hispanic Whites. Our
findings have implications for characterization of features in studies linking
cortisol to health outcomes. The presence of variability over time suggests
opportunities for future investigation of the predictors of changes over time as
well as the links between these changes and health outcomes.
PMID- 25137488
TI - Boronate affinity nanoparticles for nucleoside separation.
AB - Boronate affinity systems have been recently used for the specific isolation of
cis-diol group carrying biomolecules such as glycoproteins, nucleosides,
carbohydrates. Nanosized materials have been extremely used for the
biotechnological purposes due to their unique properties and their high surface
areas. The objective of this presented work was to develop a new boronate
affinity system for the nucleoside adsorption. For this purpose, poly(HEMA)
nanoparticles were synthesized by using surfactant free emulsion polymerization
technique and then functionalized with phenylboronic acid. Synthesized
nanoparticles were characterized with FTIR, SEM, and Zeta size analysis. Nucleic
acid adsorption experiments were repeated for different medium pH values, for
various nucleosides concentrations, for different temperatures and ionic
strengths, in order to determine the optimum adsorption conditions. In the light
of these studies, it can be concluded that this boronate ligand carrying
nanoparticles were very valuable for the separation of nucleosides.
PMID- 25137490
TI - Geo-engineering in lakes: a crisis of confidence?
PMID- 25137489
TI - Advances in preparation and characterization of chitosan nanoparticles for
therapeutics.
AB - CONTEXT: Polymers have been largely explored for the preparation of nanoparticles
due to ease of preparation and modification, large gene/drug loading capacity,
and biocompatibility. Various methods have been adapted for the preparation and
characterization of chitosan nanoparticles. OBJECTIVE: Focus on the different
methods of preparation and characterization of chitosan nanoparticles. METHODS:
Detailed literature survey has been done for the studies reporting various
methods of preparation and characterization of chitosan nanoparticles. RESULTS
AND CONCLUSION: Published database suggests of several methods which have been
developed for the preparation and characterization of chitosan nanoparticles as
per the application.
PMID- 25137487
TI - Illuminating breast cancer invasion: diverse roles for cell-cell interactions.
AB - Metastasis begins when tumors invade into surrounding tissues. In breast cancer,
the study of cell interactions has provided fundamental insights into this
complex process. Powerful intravital and 3D organoid culture systems have emerged
that enable biologists to model the complexity of cell interactions during cancer
invasion in real-time. Recent studies utilizing these techniques reveal distinct
mechanisms through which multiple cancer cell and stromal cell subpopulations
interact, including paracrine signaling, direct cell-cell adhesion, and
remodeling of the extracellular matrix. Three cell interaction mechanisms have
emerged to explain how breast tumors become invasive: epithelial-mesenchymal
transition, collective invasion, and the macrophage-tumor cell feedback loop.
Future work is needed to distinguish whether these mechanisms are mutually
exclusive or whether they cooperate to drive metastasis.
PMID- 25137491
TI - Recent developments in biological activities of chalcones: a mini review.
AB - Chalcones represent key structural motif in the plethora of biologically active
molecules including synthetic and natural products. Synthetic manipulations of
chalcones or their isolation from natural sources are being investigated
worldwide for the development of more potent and efficient drugs for the
treatment of several dreadful diseases such as cancer, diabetes, HIV,
tuberculosis, malaria etc. Over the past few years, a large volume of research
papers and review articles highlighting the significance of chalcone derivatives
has been compiled in the literature. The present review article focuses on the
recent developments (2010-2014) on various pharmacological and medicinal aspects
of chalcones and their analogues.
PMID- 25137492
TI - Apoptosis and necrosis in the circumventricular organs after experimental
subarachnoid hemorrhage as detected with annexin V and caspase 3 immunostaining.
AB - OBJECTIVES: The circumventricular organs (CVOs) are essential for most autonomic
and endocrine functions. Trauma and bleeding can affect their function. The aim
of this study was to investigate apoptosis and necrosis in CVOs in the early
period after experimental subarachnoid hemorrhage (SAH) in rats, using annexin V
affinity and caspase 3 immunostaining. METHODS: Three experimental groups were
used: Days 1 and 2 after SAH, and a control group, seven Wistar albino rats each.
Subarachnoid hemorrhage was accomplished by transclival basilar artery puncture.
Rats were perfused with 0.9% NaCl and 0.1M phosphate buffer pH 7.4 until heart
stoppage. Apoptosis and necrosis in CVOs were measured by flow cytometry with
annexin V staining, and by caspase 3 immunostaining. RESULTS: Apoptosis in the
organum vasculosum lamina terminalis (OVLT), median eminence (ME), and area
postrema (AP) was significantly higher in the Day 1 group than in the control
group. Apoptosis in the subfornicial organ (SFO), OVLT, ME, and AP was
significantly higher in the Day 2 group than in the control group. There were
significant differences between the Day 1 and Day 2 groups, except for AP.
Necrosis in SFO and OVLT was significantly higher in the Day 2 group than in the
Day 1 or control groups, whereas necrosis in the ME and AP did not differ between
the three groups. Caspase 3-positive cell density was more intense in the Day 2
group than in the Day 1 and control groups. DISCUSSION: Prevention of apoptosis
may potentially improve impaired functions of CVOs after SAH.
PMID- 25137494
TI - Multilayered modeling of particulate matter removal by a growing forest over
time, from plant surface deposition to washoff via rainfall.
AB - Airborne fine particulate matter (PM) is responsible for the most severe health
effects induced by air pollution in Europe. Vegetation, and forests in
particular, can play a role in mitigating this pollution since they have a large
surface area to filter PM out of the air. Many studies have solely focused on dry
deposition of PM onto the tree surface, but deposited PM can be resuspended to
the air or may be washed off by precipitation dripping from the plants to the
soil. It is only the latter process that represents a net-removal from the
atmosphere. To quantify this removal all these processes should be accounted for,
which is the case in our modeling framework. Practically, a multilayered PM
removal model for forest canopies is developed. In addition, the framework has
been integrated into an existing forest growth model in order to account for
changes in PM removal efficiency during forest growth. A case study was performed
on a Scots pine stand in Belgium (Europe), resulting for 2010 in a dry deposition
of 31 kg PM2.5 (PM < 2.5 MUm) ha(-1) yr(-1) from which 76% was resuspended and
24% washed off. For different future emission reduction scenarios from 2010 to
2030, with altering PM2.5 air concentration, the avoided health costs due to
PM2.5 removal was estimated to range from 915 to 1075 euro ha(-1) yr(-1). The
presented model could even be used to predict nutrient input via particulate
matter though further research is needed to improve and better validate the
model.
PMID- 25137495
TI - Tears of the rotator cuff. Causes--diagnosis--treatment.
AB - Rotator cuff ruptures are the most common degenerative tendon injury and occur
mainly in older patients as multifactorial disorders manifesting the main
symptoms of pain and restricted range of motion. Thorough clinical examination of
the shoulder includes testing the function of the rotator cuff and leads to a
tentative clinical diagnosis that is the prerequisite for diagnostic imaging
procedures. Sonography of the shoulder gives rapid access to a very good
sensitive overview of the rotator cuff. Conventional radiological imaging permits
differential diagnosis since a reduced acromiohumeral interval is understood as a
direct sign of rotator cuff rupture. The gold standard in imaging diagnostics is
MRI because it not only delivers images of rotator cuff defects, but also permits
interpretation of degenerative changes in the musculature. Significant pain
relief can be achieved by conservative therapy such as analgesia, manual therapy
and physiotherapeutic exercises and leads to improvements in the active range of
motion. Persistent pain or progressive pain during conservative therapy are
indications for surgical intervention. Arthroscopy-assisted treatment is tissue
friendlier than open surgery and is today considered the standard for surgical
treatment of rotator cuff rupture because of higher patient acceptance. Recent
studies report that surgical rotator cuff repair leads to significant improvement
in function, pain relief, and greater patient satisfaction. The principles of
postoperative care after surgical rotator cuff repair are immobilization and
gradual loading with passive and active exercises.
PMID- 25137493
TI - Vitamin D status and predictors of serum 25-hydroxyvitamin D concentrations in
Western Australian adolescents.
AB - Despite the importance of skeletal growth during adolescence, there is limited
research reporting vitamin D status and its predictors in adolescents. Using
prospective data from the Western Australian Pregnancy Cohort (Raine) Study, we
investigated vitamin D status and predictors of serum 25-hydroxyvitamin D
(25(OH)D) concentrations in adolescents. Serum 25(OH)D concentrations were
measured in the same participants at 14 and 17 years (n 1045 at both time
points). The percentage of adolescents with serum 25(OH)D concentrations < 50, 50
74.9 and >= 75 nmol/l was reported year-round and by month of blood collection.
We examined the predictors of serum 25(OH)D concentrations, including sex, race,
month of blood collection, physical activity, BMI, family income, and Ca and
vitamin D intakes (n 919 at 14 years; n 570 at 17 years), using a general linear
mixed model. At 14 years, 31 % of adolescents had serum 25(OH)D concentrations
between 50 and 74.9 nmol/l and a further 4 % had concentrations < 50 nmol/l. At
17 years, 40 % of adolescents had serum 25(OH)D concentrations between 50 and
74.9 nmol/l and 12 % had concentrations < 50 nmol/l. Caucasian ethnicity, being
sampled at the end of summer, exercising more, having a lower BMI, a higher Ca
intake and a higher family income were significantly associated with higher serum
25(OH)D concentrations. The proportion of adolescents with serum 25(OH)D
concentrations < 50 nmol/l was low in this Western Australian cohort. There is a
need for international consensus on defining adequate vitamin D status in order
to determine whether strategies to increase vitamin D status in adolescents are
warranted.
PMID- 25137496
TI - Biomechanical and biological aspects of defect treatment in fractures using
helical plates.
AB - The clinical case of figure 1 through figure 11 shows a series of impressive
failures of plate fixation. The plates were repeatedly applied bridging a
comminuted bone segment in a heavy patient. The biomechanical analysis elaborates
why this happened and proposes an unconventional procedure to prevent this
failure with a minimally invasive procedure. A plate bridging an open gap or a
defect in a long bone diaphysis is exposed to full functional load. According to
clinical observations such plate application often fails even without external
load such as weight bearing. The plate risks to break through fatigue when
exposed during a long time to cyclic loading. This type of failure has been
observed even with broad plates as well in femoral as in tibiae. The first option
to avoid such failure consists in protecting the plate by installing load sharing
between plate and either bone or an additional implant. This reduces the load
carried by the plate to a safe level. Load sharing with bone may be installed at
surgery by establishing solid mechanical bridge between the two main fragments of
the fractured bone. The optimal load sharing relies on a solid compressed contact
between the main fragments. It can be established because the bone is able to
take a large load which results in optimal protection of the plate. In the case
of an extended comminuted bone segment it may be very difficult, traumatizing and
inefficient to reconstruct the bone. In the present case it was impossible to
establish load sharing through the bone. The second option protecting the plate
is provided by callus bridging of the gap or defect. The formation of a solid
callus bridge takes time but the fatigue failure of the plate also takes time.
Therefore, the callus bridge may prevent a late fatigue failure. The surgeon may
select one of several options: - Replacing the lack of bone support using a
second plate which immediately alleviates plate loading. The drawback of
application of a second conventional plate is the extent of surgical trauma at
the critical site of healing. - Shingling and/or applying an autologous
cancellous bone graft: This procedure provides initially no relevant load sharing
but will do so after a couple of weeks. The mechanical coupling of the comparably
soft graft and the main fracture fragments presents little problems. Applying a
cortical bone graft: Such a graft does provide initial only small load sharing
and does a less good job inducing callus than a cancellous graft. Furthermore,
the coupling by callus between a somewhat rigid bone graft and the mobile main
fracture fragments requires a solid maintained contact. If the cortical graft is
fixed using implants with small contact area to the graft such as screws or
cerclage loops, the local stress may be critical and the graft may break. When
the cortical graft is fixed with cerclage wires the procedure must take into
account the limited strength of the individual cerclage. Therefore multiple and
well-spaced cerclages are required and may lead to success especially if an
intramedullary component of the implant contributes to protection (6). The degree
of unloading depends apparently on the stiffness of the material of the
protecting splint. Though, more important is the effect of the dimensions of the
splint. While titanium as a material is about 50% less stiff than steel, the
thickness of the implant changes the stiffness with the third power. That is
doubling the thickness results in eightfold increased stiffness. When considering
the unloading by application of a second plate the leverage of the second plate
plays an important role. The larger the distance between the axis of bending and
the second implant the larger the protecting effect. The helical plate (2, 3, 7)
as introduced by A.A.D. Fernandez offers biological and mechanical advantages. It
can be applied without touching the fracture site maintaining the critical
biology intact and provides mechanically efficient unloading. Its application is
fairly simple: The helical plate is modified conventional long and small plate
that is twisted between its ends about 90 degrees. The twist is applied using
"bending irons" (4, 5, 8) whereby the force required is small and the exact
degree of twist is not critical. Therefore the twist is applicable operating
bending irons by hand. Assuming a situation where a plate bridging a defect or
non-union has failed the broken plate is replaced by a similar implant: At the
distal end of the bone fracture and opposite to the surgical approach a small
incision allows to slide in the helical plate in such a way that proximally the
plate ends on the same side of the limb as the replaced plate. Ideally the two
plate ends meet and the application of the helical plate does not ask for an
additional surgical exposure at this location. Otherwise a small minimally
invasive exposure is required. The helical plate is then fixed to the main bone
fragments using a couple of locked screws. The following case demonstrates the
use and efficiency of the helical plate saving a situation where multiple
attempts using conventional plates had failed. The successful final treatment of
this case was performed by A. A. D. Fernandez.
PMID- 25137497
TI - Determining the risk of falling in elderly patients undergoing hip fracture
surgery.
AB - PURPOSE OF THE STUDY This study examines the risk of falling in elderly patients
who underwent hip fracture surgery in the orthopaedic clinic during the
postoperative period. MATERIALS AND METHODS This study was a cross-sectional
study. The study sample consisted of 71 elderly patients aged more than 65 years
undergoing hip fracture surgery. A questionnaire, the Tinetti balance test and
the mini-mental state examination (MMSE) were used. RESULTS The analyses included
71 elderly patients with a mean age of 78.45 years. All patients had been
hospitalized for hip fracture due to falling, and 29.6% had a history of falling
in the one year prior to hospitalization. The mean MMSE score was 18.37 +/- 6.54
and the mean Tinetti score was 11.10 +/- 6.66. CONCLUSION We found that as the
mean age of the elderly patients increased, the risk of falling also increased
and the MMSE scores deteriorate and that the elderly patients living alone were
at a greater risk of falling and had worse cognitive function, that those with a
history of falling before hospitalization were at a greater risk of falling again
and that the risk of falling increased as cognitive function declined. Key
words:elderly, falling, hip fracture, risk of falling.
PMID- 25137498
TI - [The effect of central anatomical single-bundle versus anatomical double-bundle
reconstruction of the anterior cruciate ligament on knee stability. a clinical
study].
AB - PURPOSE OF THE STUDY A comparison of the efficacy of central anatomical single
bundle (CASB) reconstruction with that of double-bundle (DB) repair of the
anterior cruciate ligament (ACL) in relation to knee stability in anteroposterior
translation (APT), internal rotation (IR) and external rotation (ER) of the
joint. MATERIAL AND METHODS A total of 40 patients were evaluated; 20 had ACL
reconstruction by the CASB technique using hamstrings and 20 underwent DB repair
surgery. The average age was 31.3 years, and the group included 22 men and 18
women with 19 right and 21 left knees. The KT-1000 test was used to assess the
amount of APT in the knee and rotational deviations were measured by the
Rolimeter. In the DB patients, measurements were performed before surgery (on
joints with ACL injury), then after reconstruction of the anteromedial (AM) or
the posterolateral (PL) bundle and subsequently after repair of both ACL bundles.
The CASB patients were assessed before and after graft insertion. RESULTS The
average APT value was 18.5 mm for the pre-operative knees and it fell to 8.9 mm
after AM bundle reconstruction. However, when the PL bundle was inserted in the
first place, the average APT value was 13.1 mm only. The average values recorded
after the DB and CASB reconstructions were 6.1 mm and 9.1 mm, respectively. The
average IR range of motion in the pre-operative joints was 18.6 degrees. After AM
bundle reconstruction it was 13.9 degrees and after PL bundle repair it was 15.3
degrees. In DB reconstruction the average IR value achieved 10.4 degrees, and in
CASB repair surgery it was 13.7 degrees. The average ER range of motion in the
pre-operative joints was 17.8 degrees. After AM bundle reconstruction it was 14.5
degrees and after PL bundle repair it was 14.9 degrees. In DB reconstruction the
average ER value achieved 11.4 degrees, and in CASB repair surgery it was 14.5
degrees. DISCUSSION Rotational stability of the knee after ACL reconstruction is
one of the most important factors in restoring physiological kinematics of the
joint after ACL injury. Since there are not many studies comparing knee
rotational stability after CASB with that after DB reconstructions, the results
presented here may contribute to selecting the optimal method of ACL
reconstruction. CONCLUSIONS The results show that, in ACL reconstruction, the DB
technique provides better stability to the knee, in both APT and rotation, than
the CASB method. The latter has the same effect on knee stability as the presence
of the AM bundle alone. When the PL bundle is added, knee stability, in both APT
and internal/external rotation, is increased in comparison with central single
bundle ACL repair. Key words:anterior cruciate ligament, navigation, central
anatomical single-bundle reconstruction, double-bundle reconstruction.
PMID- 25137499
TI - [The angular profile of a cage has no influence on segmental alignment after
anterior cervical stand-alone interbody fusion].
AB - PURPOSE OF THE STUDY: The original aim of this prospective semi-randomised study
was to determine associations between segmental sagittal alignment after Anterior
Cervical Discectomy and Fusion (ACDF) and subjective and clinical results. Two
types of cages, cage P with parallel end-plates and cage A with 5-degree
angulations, were used in the patients treated for degenerative conditions.
MATERIAL AND METHODS: A total of 94 consecutive patients, 56 treated by single
level ACDF and 38 undergoing a two-level procedure, completed 8 years of follow
up. The patients in equally-sized A and P subgroups were examined at 6 weeks and
1, 2 and 8 years after surgery. The follow-up included X-ray in a neutral lateral
position, a questionnaire assessing pain in neck and shoulder regions and JOA
scores. The results including the cumulative incidence of surgical procedures
indicated for adjacent segment diseases were statistically evaluated. RESULTS: An
average increase in the lordotic angle at 6 weeks after surgery was 2.32 degrees
for the implant P and 2.02 degrees for the implant A subgroup. During 8 years of
follow-up the average values decreased to 1.51 degrees and 1.36 degrees ,
respectively. The proportion of patients with no or minimal neck and shoulder
pain decreased, in subgroup P, from the initial 85% at 6 weeks to 59% at 8 years
after the surgery and, in subgroup A, from 89% to 40 %. The average JOA score of
16 at 6 weeks in both subgroups, at 8 years, had a value of 15.9 in subgroup P
and 16.0 in subgroup A. The cumulative incidence of surgery for adjacent segment
disease 8 years was 8.3% for subgroup P and 6.3% for subgroup A. No statistically
significant differences between the subgroups at any follow-up period were
recorded in either morphological characteristics or clinical outcomes.
CONCLUSIONS: The ability to lordotize a segment by stand-alone ACDF is below the
angular resolution of current radiographic methods, irrespective of the sagittal
profile of the implant used. Comparable morphological results haven't been
reflected by significant difference in subjective and clinical outcome and also
in the incidence of surgery for adjacent segment disease. Such results were not
expected and therefore post-operative sagittal alignment mechanisms in stand
alone cage assisted ACDF will require further investigation. Key words:cervical
vertebrae, surgical technique, spinal fusion, sagittal alignment, clinical
outcome.
PMID- 25137500
TI - Epithelioid osteosarcoma of the scapula.
AB - Epithelioid and epithelial neoplasms of bone are rare. They include different
epithelioid variants of vascular lesions, osteoblastoma, chondroblastoma and most
importantly metastatic carcinoma. Up to now, only few cases of epithelioid
osteosarcoma were described. In this case the authors report a 53-year-old
patient presented with a medical history of chronic shoulder pain for 3 years.
Magnetic resonance imaging (MRI and computed tomography (CT) showed a
destructive, partially calcified osseous lesion of the scapula with expansion
into the surrounding soft tissue, suggestive of a primary bone tumor.
Histologically, the tumor consisted of epithelioid cells with expression of
cytokeratine and the lesion was primarily diagnosed as metastatic carcinoma. With
regard to the MRI morphology untypical for metastatic disease the histopathologic
slides were re-evaluated and detection of tumor osteoid led to the diagnosis of
epithelioid osteosarcoma. Chemotherapy was initiated, however follow-up imaging
studies showed rapidly progressive disease of both primary tumor and lung
metastases. In conclusion, epithelioid neoplasms of the bone are extremetumourly
rare and must be distinguished from metastatic carcinoma. Despite the presence of
cytokeratine positive cells a thorough histological evaluation is mandatory and
osteoid detection is essential in order to establish the correct diagnosis and
further treatment. Key words: osteosarcoma, epithelioid, aneurysmal bone cyst,
chondrosarcoma, pathology, immunohistochemistry.
PMID- 25137501
TI - [Surgical treatment of ischial apophysis avulsion. Case report].
AB - The optimal management of ischial apophysis avulsion, especially indications for
surgery, is not well defined. The authors present the case of a 16-year-old man
who sustained an avulsion fracture of the ischial apophysis during his athlete
training programme. The avulsion was diagnosed by X-ray. Because of displacement,
surgery was indicated and open reduction with osteosynthesis was performed using
a subgluteal approach on the eighth day after injury. Full weight bearing was
allowed at nine weeks after injury, after the post-operative rehabilitation
programme had been completed. Return to his sports activity was allowed at four
months after injury. At one post-operative year the patient was free of any
symptoms. The proper surgical treatment of a displaced ischial apophysis avulsion
and subsequent rehabilitation allow for early full weight bearing, including
sports activities. The subgluteal approach provides good access to the ischial
tuberosity with a minimal risk of complications and a good cosmetic outcome. Key
words:apophysis, ischial tuberosity, avulsion.
PMID- 25137502
TI - Engineering the interfaces of ITO@Cu2S nanowire arrays toward efficient and
stable counter electrodes for quantum-dot-sensitized solar cells.
AB - Among the issues that restrict the power conversion efficiency (PCE) of quantum
dot-sensitized solar cells (QDSSCs), insufficient catalytic activity and
stability of counter electrodes (CEs) are critical but challenging ones. The
state-of-the-art Cu/Cu2S CEs still suffer from mechanical instability and
uncertainty due to the reaction of copper and electrolyte. Herein, ITO@Cu2S core
shell nanowire arrays were developed to fabricate CEs for QDSSCs, which have no
such issues in Cu/Cu2S CEs. These nanowire arrays exhibited small charge transfer
resistance and sheet resistance, and provided more active catalytic sites and
easy accessibility for electrolyte due to the three-dimensional structure upon
use as CEs. More interestingly, it was found that the interface of ITO/Cu2S
significantly affected the performance of ITO@Cu2S nanowire array CEs. By varying
synthetic methods, a series of ITO@Cu2S nanowire arrays were prepared to
investigate the influence of ITO/Cu2S interface on their performance. The results
showed that ITO@Cu2S nanowire array CEs with a continuous Cu2S nanocrystal shell
fabricated via an improved cation exchange route exhibited excellent and
thickness-dependent performance. The PCE of corresponding QDSSCs increased by
11.6 and 16.5% compared to that with the discrete Cu2S nanocrystal and the
classic Cu/Cu2S CE, respectively, indicating its promising potential as a new
type of CE for QDSSCs.
PMID- 25137503
TI - A silver nanoparticle embedded hydrogel as a substrate for surface contamination
analysis by surface-enhanced Raman scattering.
AB - A surface enhanced Raman scattering (SERS) substrate, capable of extracting small
amounts of organic species from surfaces of different types of materials with
variable roughness, has been fabricated. The substrate consists of Ag NPs
encapsulated in poly(vinyl alcohol) (PVA) hydrogels, commonly known as PVA
"slime". Unlike traditional SERS substrates, such as colloidal suspensions, the
resulting PVA slime SERS substrate presents good viscoelasticity, allowing it to
conform to the surface of various materials of arbitrary roughness. Surfaces of
different materials, including sandpapers, cotton, metal, and wood, previously
contaminated with nile blue A (NBA) were analyzed with the PVA slime SERS
substrate. Limits of detection (LOD) as low as 100 ppb (0.79 ng in a total amount
on an area of ~3 cm(2)) were achieved for all surfaces tested. Pesticides and
Sudan red III on the glass surface have also been detected, with a LOD of 1.6 ng
per ~3 cm(2).
PMID- 25137504
TI - From theory to evidence: long-term evaluation of the mechanism of action and flap
integration of distal vascularized lymph node transfers.
AB - BACKGROUND: Nonanatomic (distal) placement of vascularized lymph node (VLN)
transfers have shown efficacy in the treatment of extremity lymphedema, but the
mechanism by which these flaps provide relief of lymphedema remains unclear.
Intrinsic lymphovenous connections have been previously shown to exist in the
transferred flap. But, the long-term interaction of the VLN flap and surrounding
lymphedematous extremity has not been previously investigated. PATIENTS AND
METHODS: A retrospective review of a prospective maintained database of patients
who underwent VLN transfer was evaluated. Patients who underwent distal VLN
transfer and had more than 1-year follow-up were identified. Lymphodynamic
evaluation was performed using 0.3 to 0.6 mL indocyanine green (ICG) injection at
5 cm proximal to the flap edge on identified patients. Migration direction of dye
and latency period was evaluated. RESULTS: In total, 20 patients were identified
who met inclusion criteria. Average long-term follow-up was 27.3 months. The
average circumference reduction of the affected extremity was 40.5%. ICG
appearance within the VLN flap was found in all patients occurring on average in
178.3 seconds. In all cases, flow occurred in the distal direction (toward the
flap) with proximal placement of dye. Latency period was found to inversely
correlate with circumference reduction (p < 0.01). CONCLUSIONS: Distal,
nonanatomic placement of VLN flaps provide sustained limb circumference reduction
in extremity lymphedema patients following a minimum of 1-year postoperatively.
Flap integration with the recipient site reliably occurs as witnessed with
consistent ICG drainage, and occurs in the gravity-dependent direction. Faster
clearance of ICG will result in improved clinical limb circumference reduction.
PMID- 25137505
TI - Vitamin D and skeletal muscle function in athletes.
AB - PURPOSE OF REVIEW: To highlight recently published data about the vitamin D
status of athletes, and effect of vitamin D supplementation on muscle strength
and performance in the athletic population.The vitamin D receptor exists in
skeletal muscle, and muscle weakness has been reported in individuals who are
severely deficient [25(OH)D <25 nmol/l]. Experimental findings reveal the
cellular and genomic mechanisms implicating vitamin D in muscle mass, strength
and function, and raise questions about the role of vitamin D in the achievement
of optimum athletic performance. RECENT FINDINGS: Athletes appear to have the
same risk of vitamin D deficiency and seasonal variance in status as nonathletic
members of the same population, with the exception of athletes who train and
compete indoors whose risk of deficiency is somewhat greater. Interventions with
vitamin D supplements have had mixed results, with a positive effect on muscle
function observed only in participants with insufficient status [25(OH)D <50
nmol/l]. SUMMARY: There have been relatively few robust interventions with
vitamin D supplementation in athletic populations who are vitamin D deficient,
and none which have been able to establish the ideal 25(OH)D concentration for
optimum performance.
PMID- 25137506
TI - Development of personalized functional foods needs metabolic profiling.
AB - PURPOSE OF REVIEW: There is growing interest in applying metabolic profiling
technologies to food science as this approach is now embedded into the foodomics
toolbox. This review aims at exploring how metabolic profiling can be applied to
the development of functional foods. RECENT FINDINGS: One of the biggest
challenges of modern nutrition is to propose a healthy diet to populations
worldwide that must suit high inter-individual variability driven by complex gene
nutrient-environment interactions. Although a number of functional foods are now
proposed in support of a healthy diet, a one-size-fits-all approach to nutrition
is inappropriate and new personalized functional foods are necessary. Metabolic
profiling technologies can assist at various levels of the development of
functional foods, from screening for food composition to identification of new
biomarkers of food intake to support diet intervention and epidemiological
studies. SUMMARY: Modern 'omics' technologies, including metabolic profiling,
will support the development of new personalized functional foods of high
relevance to 21st century medical challenges, such as controlling the worldwide
spread of metabolic disorders and ensuring healthy ageing.
PMID- 25137507
TI - High-sensitivity C-reactive protein (hs-CRP) levels and its relationship with
components of polycystic ovary syndrome in Indian adolescent women with
polycystic ovary syndrome (PCOS).
AB - C-reactive protein (CRP) is a risk marker for type 2 diabetes mellitus and
cardiovascular diseases. In polycystic ovary syndrome (PCOS), limited data are
available on high-sensitivity C-reactive protein (hs-CRP) levels and its
relationship with components of PCOS especially in Indian women. The objective
was to determine serum hs-CRP concentration in adolescent women with and without
PCOS and to assess possible correlations of serum hs-CRP levels with components
of PCOS in Indian women. One hundred and sixty women with PCOS and sixty non-PCOS
women having normal menstrual cycles were included. Clinical assessment included
anthropometry, Ferriman-Gallwey (FG) score and blood pressure (BP) measurement.
Laboratory evaluation included estimation of T4, TSH, LH, FSH, total
testosterone, prolactin, cortisol, 17OHP, hs-CRP, lipid profile, and insulin, and
glucose after 2-h oral glucose tolerance test. Homeostasis Model Assessment
Insulin resistance index (HOMA-IR) and Quantitative Insulin Sensitivity Check
Index (QUICKI) and glucose intolerance was calculated. FG score, LH, FSH, total
Testosterone, HOMA-IR and QUICKI were significantly different among women with or
without PCOS (p < 0.01). Although hs-CRP levels showed a higher trend in women
having PCOS, there was no significant difference between the groups (p > 0.05). A
significant and positive correlation was found between hs-CRP and body mass index
(BMI) (r = 0.308, p < 0.01) among PCOS group. The results in Indian adolescent
women suggest that hs-CRP levels may not per se be associated with PCOS, rather
can be related to fat mass in this subset of subjects.
PMID- 25137508
TI - Discordant phenotype in monozygotic female twins with Lys35Thr TTR familial
amyloidotic polyneuropathy.
AB - Familial amyloidotic polyneuropathy is the hereditary form of transthyretin
amyloidosis that is rapidly progressive. Discordant expression of Val30Met
transthyretin amyloid in monozygotic twins has been reported in the past, in
Europe and Asia. We report the first case of discordant expression of Lys35Thr
transthyretin amyloid in female monozygotic twins in North America with eye
involvement and peripheral neuropathy.
PMID- 25137509
TI - Dermatomyositis-associated sensory neuropathy: a unifying pathogenic hypothesis.
AB - Neuropathy as extramuscular manifestation of dermatomyositis (DM) is
controversial due to uncommon occurrence, heterogeneity of associated nerve
pathology, and lack of unifying pathogenetic mechanism(s). We describe a patient
with classic manifestations of DM and extramuscular manifestation of neuropathy.
Nerve pathology showed deposits of terminal complement complex (C5b-9). Her
examination showed mild proximal weakness, rash, and sensory impairment in
fingertips, toes, and nose. EMG/NCS revealed irritable myopathy and mild sensory
neuropathy. Muscle biopsy showed features suggestive of DM, including deposition
of C5b-9. CK was elevated to 214 and ANA was positive at 1:160. Etiological work
up for neuropathy, including diabetes, was negative. Sural nerve biopsy at light
level revealed very mild large fiber sensory neuropathy. EM showed moderately
severe involvement of small sensory fibers. Neuropathy may be an underrecognized
manifestation of DM. Nerve pathology demonstrating complement-mediated damage
could be a unifying mechanism of muscle and nerve injury.
PMID- 25137510
TI - Small fiber abnormalities in skin biopsies of patients with benign
fasciculations.
AB - OBJECTIVE: To determine whether patients with benign fasciculations have evidence
for axonal loss in skin biopsies. METHODS: Epidermal sensory and sweat gland
nerve fiber densities were quantified in skin biopsies of 11 patients with benign
fasciculations and no other known cause for neuropathy. RESULTS: Nine of the 11
patients (82%) had significantly reduced epidermal or sweat gland nerve fiber
densities at the calf or thigh, in comparison with control values. CONCLUSIONS:
The presence of reduced epidermal and sweat gland nerve fiber density indicates
the presence of axonal loss in patients with benign fasciculations.
PMID- 25137511
TI - Neuromuscular pathology case.
PMID- 25137512
TI - Rare case of a localized radial nerve amyloid neuropathy.
AB - We report the case of a 55-year-old woman with a 6-month history of progressive
paresis of the right radial nerve. Perioperative imaging detected a spindle
shaped expansion of the radial nerve caused by an isolated local deposit of
amyloid (amyloidoma). The deposit was resected in 2 phases and the resulting
defect was bridged by a sural nerve autograft. Overall internal and hematological
examination did not reveal systemic amyloidosis or lymphoproliferative disorder.
The reason for our report is that localized forms of amyloid neuropathy are very
rare.
PMID- 25137513
TI - Spinal magnetic resonance imaging in chronic poliomyelitis.
PMID- 25137514
TI - Revisiting the evidence for neuropathy caused by pyridoxine deficiency and
excess.
AB - Pyridoxine deficiency and excess have been implicated as a cause for peripheral
neuropathy. As a result, unrelated neuropathies are often treated with pyridoxine
based on questionable evidence. However, neurological practitioners frequently
discourage patients from taking pyridoxine in excess of 50 mg/d given concerns
around the development of a toxic sensory neuronopathy. There is no systematic
review to support either of the 2 practices. To address this gap in knowledge, we
reviewed the available literature on neuropathy attributed to pyridoxine
deficiency and excess. Based on the current limited data, it can be concluded
that very low doses of daily pyridoxine are required to prevent peripheral
neuropathy. There is inadequate evidence to support routine pyridoxine
supplementation in patients with disorders of peripheral nervous system.
Supplementation with pyridoxine at doses greater than 50 mg/d for extended
duration may be harmful and should be discouraged.
PMID- 25137516
TI - Appearance of thymoma 5 years after thymectomy for nonthymomatous myasthenia
gravis.
PMID- 25137517
TI - A case of an African American man with ataxia and oculomotor apraxia 2.
PMID- 25137518
TI - Solid-phase microextraction of phthalate esters by a new coating based on a
thermally stable polypyrrole/graphene oxide composite.
AB - A novel polypyrole/graphene oxide coating was made by the electrochemical
polymerization of pyrrole in the presence of sodium dodecyl sulfate and graphene
oxide on a platinum wire. The prepared fiber has shown a good thermal stability
up to 300 degrees C. The fiber was applied to the direct solid-phase
microextraction and gas chromatographic analysis of four phthalate esters. The
effect of four parameters on gas chromatography peak area including extraction
temperature, extraction time, injection temperature, and ionic strength were
investigated. Under the optimized conditions, the detection limits were between
0.042 and 0.26 MUg/L. The intraday and interday relative standard deviations
obtained at 55 MUg/L, using a single fiber, were 8.2-16% and 17.3-25.6%,
respectively. The method was successfully applied to the analysis of phthalate
esters in two real samples of boiling water in cheap disposable clear plastic
drinking cups showing recoveries from 83 to 120%.
PMID- 25137519
TI - Advance in PD research explored a new field on ubiquitin biology.
PMID- 25137520
TI - Heavy metals, organic solvents, and multiple sclerosis: An exploratory look at
gene-environment interactions.
AB - Exposure to heavy metals and organic solvents are potential etiologic factors for
multiple sclerosis (MS), but their interaction with MS-associated genes is under
studied. The authors explored the relationship between environmental exposure to
lead, mercury, and solvents and 58 single-nucleotide polymorphisms (SNPs) in MS
associated genes. Data from a population-based case-control study of 217
prevalent MS cases and 496 age-, race-, gender-, and geographically matched
controls were used to fit conditional logistic regression models of the
association between the chemical, gene, and MS, adjusting for education and
ancestry. MS cases were more likely than controls to report lead (odds ratio [OR]
= 2.03; 95% confidence interval [CI]: 1.07, 3.86) and mercury exposure (OR =
2.06; 95% CI: 1.08, 3.91). Findings of potential gene-environment interactions
between SNPs in TNF-alpha, TNF-beta, TCA-beta, VDR, MBP, and APOE, and lead,
mercury, or solvents should be considered cautiously due to limited sample size.
PMID- 25137522
TI - Safety of minimally invasive radical prostatectomy in patients with prior
abdominopelvic or inguinal surgery.
AB - INTRODUCTION: Despite the widespread use of minimally invasive radical
prostatectomy (MIRP), there remain concerns regarding its safety in patients with
a history of prior abdominopelvic or inguinal surgery. METHODS: A prospective
database of 1165 MIRP procedures performed by a single surgeon at a high-volume
tertiary care center from 2001 to 2013 was analyzed. After an initial period of
transperitoneal MIRP (TP), an extraperitoneal (EP) approach was used
preferentially beginning in 2005 (for both laparoscopic and robotic cases), and
robotics were used preferentially beginning in 2010. Overall perioperative
complications, major complications (Clavien-Dindo III or IV), and abdominal
complications (e.g., ileus, bowel/organ injury, or vascular injury) were compared
for patients with and without a prior surgical history. Uni- and multivariate
logistic regression were used to control the impact of robotics, approach,
operative time, estimated blood loss, case number, prostate weight, and primary
Gleason on complications. RESULTS: Three hundred patients undergoing MIRP had
prior abdominopelvic or inguinal surgery (25.8%). Of these, 102 (34%) underwent
TP and 198 (66%) EP MIRP. Robotics was used in 286 cases (24.6%) and pure
laparoscopy in 879 (75.4%). Complications occurred in 111 patients (9.5%) from
the total cohort, with major complications in 32 (2.75%) and abdominal
complications in 19 (1.63%). Prior surgery was not associated with overall,
major, or abdominal complications. Of the controlling factors, only increasing
operative time was associated with postoperative abdominal complications (most of
which were ileus) on multivariate analysis. CONCLUSIONS: In this large single
surgeon series where both EP and TP approaches to MIRP are utilized, prior
abdominopelvic or inguinal surgery was not associated with an increased risk of
perioperative complications.
PMID- 25137521
TI - Amide proton transfer-weighted imaging of the head and neck at 3 T: a feasibility
study on healthy human subjects and patients with head and neck cancer.
AB - The aim of this study was to explore the feasibility and repeatability of amide
proton transfer-weighted (APTw) MRI for the head and neck on clinical MRI
scanners. Six healthy volunteers and four patients with head and neck tumors
underwent APTw MRI scanning at 3 T. The APTw signal was quantified by the
asymmetric magnetization transfer ratio (MTRasym) at 3.5 ppm. Z spectra of normal
tissues in the head and neck (masseter muscle, parotid glands, submandibular
glands and thyroid glands) were analyzed in healthy volunteers. Inter-scan
repeatability of APTw MRI was evaluated in six healthy volunteers. Z spectra of
patients with head and neck tumors were produced and APTw signals in these tumors
were analyzed. APTw MRI scanning was successful for all 10 subjects. The parotid
glands showed the highest APTw signal (~7.6% average), whereas the APTw signals
in other tissues were relatively moderate. The repeatability of APTw signals from
the masseter muscle, parotid gland, submandibular gland and thyroid gland of
healthy volunteers was established. Four head and neck tumors showed positive
mean APTw ranging from 1.2% to 3.2%, distinguishable from surrounding normal
tissues. APTw MRI was feasible for use in the head and neck regions at 3 T. The
preliminary results on patients with head and neck tumors indicated the potential
of APTw MRI for clinical applications.
PMID- 25137523
TI - Hemostatic effect of hot saline irrigation during functional endoscopic sinus
surgery: a randomized controlled trial.
AB - BACKGROUND: The endoscopically magnified operative field in functional endoscopic
sinus surgery (FESS) makes even a small amount of bleeding a potentially
significant hindrance. It is thought that irrigation with hot saline during
surgery may improve surgical field of view by producing a hemostatic effect. Our
objective was to assess the effectiveness of hot saline irrigation (HSI) compared
to room temperature saline irrigation (RTSI) in the control of intraoperative
bleeding during FESS. METHODS: Sixty-two chronic rhinosinusitis (CRS) patients
undergoing FESS were randomized to 2 treatment arms in an equal ratio. Subjects
received either HSI (49 degrees C) or RTSI (18 degrees C), 20 mL every 10
minutes, for the duration of FESS. The Boezaart endoscopic field of view grading
system was the primary outcome measure. Boezaart score, heart rate, and mean
arterial blood pressure (MABP) were recorded at 10-minute intervals between
irrigations. RESULTS: Mean endoscopic surgical field of view (Boezaart score) did
not significantly differ between the HSI and RTSI groups (1.5 +/- 0.6 vs 1.3 +/-
0.5; p = 0.23). However, when FESS was longer than 2 hours in duration, the
Boezaart scores were significantly better in the HSI group (1.6 +/- 0.6 vs 1.2 +/
0.4; p = 0.04). We found that blood loss per minute was significantly reduced (p
= 0.02) in all cases in which HSI was used (2.3 +/- 1.0) compared to RTSI (1.7 +/
1.1). Despite this, heart rate (p = 0.32) and MABP (p = 0.14) did not
significantly differ between treatment groups. CONCLUSION: HSI may be beneficial
in improving surgical field of view in FESS after 2 hours of operating time. A
significant reduction in rate of blood loss may be attained with HSI.
PMID- 25137524
TI - Direct comparison of electrochemical and spectrochemical kinetics for catalytic
oxygen reduction.
AB - We describe here a direct comparison of electrochemical and spectrochemical
experiments to determine rates and selectivity of oxygen reduction catalyzed by
iron 5,10,15,20-meso-tetraphenylporphyrin chloride. Good agreement was found
between the two methods, suggesting the same mechanism is occurring under both
conditions, with the same third-order rate law, similar selectivity, and the
derived rate constants agreeing within a factor of at most 4, with k(cat) ? 2 *
10(6) M(-2) s(-1). This Communication provides a rare example of a redox
catalytic process characterized by two common but very different methods.
PMID- 25137525
TI - Surface-initiated hyperbranched polyglycerol as an ultralow-fouling coating on
glass, silicon, and porous silicon substrates.
AB - Anionic ring-opening polymerization of glycidol was initiated from activated
glass, silicon, and porous silicon substrates to yield thin, ultralow-fouling
hyperbranched polyglycerol (HPG) graft polymer coatings. Substrates were
activated by deprotonation of surface-bound silanol functionalities. HPG
polymerization was initiated upon the addition of freshly distilled glycidol to
yield films in the nanometer thickness range. X-ray photoelectron spectroscopy,
contact angle measurements, and ellipsometry were used to characterize the
resulting coatings. The antifouling properties of HPG-coated surfaces were
evaluated in terms of protein adsorption and the attachment of mammalian cells.
The adsorption of bovine serum albumin and collagen type I was found to be
reduced by as much as 97 and 91%, respectively, in comparison to untreated
surfaces. Human glioblastoma and mouse fibroblast attachment was reduced by 99
and 98%, respectively. HPG-grafted substrates outperformed polyethylene glycol
(PEG) grafted substrates of comparable thickness under the same incubation
conditions. Our results demonstrate the effectiveness of antifouling HPG graft
polymer coatings on a selected range of substrate materials and open the door for
their use in biomedical applications.
PMID- 25137526
TI - Catalytic mechanism of bacteriophage T4 Rad50 ATP hydrolysis.
AB - Spontaneous double-strand breaks (DSBs) are one of the most deleterious forms of
DNA damage, and their improper repair can lead to cellular dysfunction. The Mre11
and Rad50 proteins, a nuclease and an ATPase, respectively, form a well-conserved
complex that is involved in the initial processing of DSBs. Here we examine the
kinetic and catalytic mechanism of ATP hydrolysis by T4 Rad50 (gp46) in the
presence and absence of Mre11 (gp47) and DNA. Single-turnover and pre-steady
state kinetics on the wild-type protein indicate that the rate-limiting step for
Rad50, the MR complex, and the MR-DNA complex is either chemistry or a
conformational change prior to catalysis. Pre-steady state product release
kinetics, coupled with viscosity steady state kinetics, also supports that the
binding of DNA to the MR complex does not alter the rate-limiting step. The lack
of a positive deuterium solvent isotope effect for the wild type and several
active site mutants, combined with pH-rate profiles, implies that chemistry is
rate-limiting and the ATPase mechanism proceeds via an asymmetric, dissociative
like transition state. Mutation of the Walker A/B and H-loop residues also
affects the allosteric communication between Rad50 active sites, suggesting
possible routes for cooperativity between the ATP active sites.
PMID- 25137527
TI - Introduction of a methodology for visualization and graphical interpretation of
Bayesian classification models.
AB - Supervised machine learning models are widely used in chemoinformatics,
especially for the prediction of new active compounds or targets of known
actives. Bayesian classification methods are among the most popular machine
learning approaches for the prediction of activity from chemical structure. Much
work has focused on predicting structure-activity relationships (SARs) on the
basis of experimental training data. By contrast, only a few efforts have thus
far been made to rationalize the performance of Bayesian or other supervised
machine learning models and better understand why they might succeed or fail. In
this study, we introduce an intuitive approach for the visualization and
graphical interpretation of naive Bayesian classification models. Parameters
derived during supervised learning are visualized and interactively analyzed to
gain insights into model performance and identify features that determine
predictions. The methodology is introduced in detail and applied to assess
Bayesian modeling efforts and predictions on compound data sets of varying
structural complexity. Different classification models and features determining
their performance are characterized in detail. A prototypic implementation of the
approach is provided.
PMID- 25137528
TI - Strong negative nanocatalysis: oxygen reduction and hydrogen evolution at very
small (2 nm) gold nanoparticles.
AB - The electron transfer kinetics associated with both the reduction of oxygen and
of protons to form hydrogen at gold nanoparticles are shown to display strong
retardation when studied at citrate capped ultra small (2 nm) gold nanoparticles.
Negative nanocatalysis in the hydrogen evolution reaction (HER) is reported for
the first time.
PMID- 25137530
TI - HPLC-UV method for quantifying etoposide in plasma and tumor interstitial fluid
by microdialysis: application to pharmacokinetic studies.
AB - A simple and sensitive bioanalytical method was developed and validated for
determination of etoposide in plasma and microdialysis samples of Walker-256
tumor-bearing rats. A microdialysis probe was implanted in the center of a
subcutaneous tumor and Ringer's solution was used as perfusion medium.
Chromatographic separation was conducted on a Shimadzu CLC-C8 column using a
mobile phase consisting of water-acetonitrile (70:30; v/v) adjusted to pH 4.0 +/-
0.1 with formic acid at a gradient flow rate of 1.0-0.6 mL/min, an injection
volume of 30 MUL and UV detection at 210 nm. Microdialysate samples were analyzed
without processing and plasma samples (100 MUL) were spiked with phenytoin as
internal standard (IS) (1 ug/mL) followed by extraction with tert-butyl methyl
ether. The organic layer was evaporated and reconstituted with 100 MUL of mobile
phase before injection. The methods for plasma and microdialysate were linear in
the ranges of 25-10,000 ng/mL and of 10-1500 ng/mL, respectively. All the
validation parameters such as intra- and inter-day precision and accuracy and
stability were within the limits established by international guidelines. The
present method was successfully applied in the investigation of etoposide
pharmacokinetics in rat plasma and microdialysate tumor samples following a
single 15 mg/kg intravenous dose.
PMID- 25137529
TI - Iminosugar C-glycoside analogues of alpha-D-GlcNAc-1-phosphate: synthesis and
bacterial transglycosylase inhibition.
AB - We herein describe the first synthesis of iminosugar C-glycosides of alpha-D
GlcNAc-1-phosphate in 10 steps starting from unprotected D-GlcNAc. A
diastereoselective intramolecular iodoamination-cyclization as the key step was
employed to construct the central piperidine ring of the iminosugar and the C
glycosidic structure of alpha-D-GlcNAc. Finally, the iminosugar phosphonate and
its elongated phosphate analogue were accessed. These phosphorus-containing
iminosugars were coupled efficiently with lipophilic monophosphates to give lipid
linked pyrophosphate derivatives, which are lipid II mimetics endowed with potent
inhibitory properties toward bacterial transglycosylases (TGase).
PMID- 25137532
TI - Halide-bridged binuclear HX-splitting catalysts.
AB - Two-electron mixed-valence compounds promote the rearrangement of the two
electron bond photochemically. Such complexes are especially effective at
managing the activation of hydrohalic acids (HX). Closed HX-splitting cycles
require proton reduction to H2 and halide oxidation to X2 to be both
accomplished, the latter of which is thermodynamically and kinetically demanding.
Phosphazane-bridged Rh2 catalysts have been especially effective at activating HX
via photogenerated ligand-bridged intermediates; such intermediates are analogues
of the classical ligand-bridged intermediates proposed in binuclear elimination
reactions. Herein, a new family of phosphazane-bridged Rh2 photocatalysts has
been developed where the halide-bridged geometry is designed into the ground
state. The targeted geometries were accessed by replacing previously used alkyl
isocyanides with aryl isocyanide ligands, which provided access to families of
Rh2L1 complexes. H2 evolution with Rh2 catalysts typically proceeds via two
electron photoreduction, protonation to afford Rh hydrides, and photochemical H2
evolution. Herein, we have directly observed each of these steps in
stoichiometric reactions. Reactivity differences between Rh2 chloride and bromide
complexes have been delineated. H2 evolution from both HCl and HBr proceeds with
a halide-bridged Rh2 hydride photoresting state. The H2-evolution efficiency of
the new family of halide-bridged catalysts is compared to a related catalyst in
which ligand-bridged geometries are not stabilized in the molecular ground state,
and the new complexes are found to more efficiently facilitate H2 evolution.
PMID- 25137531
TI - EPR, ENDOR, and electronic structure studies of the Jahn-Teller distortion in an
Fe(V) nitride.
AB - The recently synthesized and isolated low-coordinate Fe(V) nitride complex has
numerous implications as a model for high-oxidation states in biological and
industrial systems. The trigonal [PhB((t)BuIm)3Fe(V)=N](+) (where (PhB((t)BuIm)3(
) = phenyltris(3-tert-butylimidazol-2-ylidene)), (1) low-spin d(3) (S = 1/2)
coordination compound is subject to a Jahn-Teller (JT) distortion of its doubly
degenerate (2)E ground state. The electronic structure of this complex is
analyzed by a combination of extended versions of the formal two-orbital pseudo
Jahn-Teller (PJT) treatment and of quantum chemical computations of the PJT
effect. The formal treatment is extended to incorporate mixing of the two e
orbital doublets (30%) that results from a lowering of the idealized molecular
symmetry from D3h to C3v through strong "doming" of the Fe-C3 core.
Correspondingly we introduce novel DFT/CASSCF computational methods in the
computation of electronic structure, which reveal a quadratic JT distortion and
significant e-e mixing, thus reaching a new level of synergism between
computational and formal treatments. Hyperfine and quadrupole tensors are
obtained by pulsed 35 GHz ENDOR measurements for the (14/15)N-nitride and the
(11)B axial ligands, and spectra are obtained from the imidazole-2-ylidene (13)C
atoms that are not bound to Fe. Analysis of the nitride ENDOR tensors
surprisingly reveals an essentially spherical nitride trianion bound to Fe, with
negative spin density and minimal charge density anisotropy. The four-coordinate
(11)B, as expected, exhibits negligible bonding to Fe. A detailed analysis of the
frontier orbitals provided by the electronic structure calculations provides
insight into the reactivity of 1: JT-induced symmetry lowering provides an
orbital selection mechanism for proton or H atom transfer reactivity.
PMID- 25137533
TI - Chronic lung disease and detection of pulmonary artery dilatation in high
resolution computerized tomography of chest in chronic arsenic exposure.
AB - Lung affection in chronic arsenicosis developing from chronic ingestion of
arsenic contaminated groundwater has been known but little is known on its effect
on pulmonary arterial system. A cross sectional study was carried out at two
geographically similar areas and demographically similar populations with or
without evidence of chronic arsenic exposure in West Bengal, India. The willing
participants in both the groups with chronic respiratory symptoms were evaluated
with High Resolution Computerized Tomography (HRCT) of Chest. Evaluation of High
Resolution Computerized Tomography of chest followed clinical assessment of lung
disease in194 and 196 subjects from the arsenic exposed and unexposed people; the
former had a higher prevalence of cough OR(Odds Ratio) 3.23 (95% CI(Confidence
Interval): 1.72-6.07) and shortness of breath OR1.76 (95% CI: 0.84-3.71),
respectively. The arsenic exposed individuals showed higher score for
bronchiectasis [mean +/- SD(Standard Deviation)] as 2.41 +/- 2.32 vs. 1.22 +/-
1.48 (P <0.001), pulmonary artery branch dilatation (PAD) as 2.48 +/- 2.33 vs.
0.78 +/- 1.56, (P <0.001) and pulmonary trunk dilatation as 0.26 +/- 0.45 vs.
nil. Age-adjusted prevalence odds ratio (POR) for Pulmonary Artery Dilatation
Found in HRCT comparing those exposed to arsenic (Group 1) to unexposed
participants (Group 2) was found to be 6.98 (CI: 2.26-16.48). There was a strong
dose-response relationship between the PAD (Pulmonary Artery Dilatation) and
cumulative arsenic exposure. Pulmonary trunk and branch dilatation in chronic
arsenicosis is a frequent abnormality seen in HRCT Chest of arsenicosis patients.
The significance of such finding needs further investigation.
PMID- 25137534
TI - Adsorption and removal of arsenic (V) using crystalline manganese (II,III) oxide:
Kinetics, equilibrium, effect of pH and ionic strength.
AB - Manganese (II,III) oxide (Mn3O4) crystalline powder was evaluated as a potential
sorbent for removal of arsenic (V) from water. Adsorption isotherm experiments
were carried out to determine the adsorption capacity using de-ionized (DI)
water, a synthetic solution containing bicarbonate alkalinity, and two natual
groundwater samples. Adsorption isotherm data followed the Langmuir and
Freundlich equations, indicating favorable adsorption of arsenic (V) onto Mn3O4,
while results from the Dubinin-Radushkevich equation were suggestive of
chemisorption of arsenic (V). When normalized to the sorbent surface area, the
maximum adsorption capacity of Mn3O4 for arsenic (V) was 101 MUg m(-2),
comparable to that of activated alumina. Arsenic (V) adsorption onto Mn3O4
followed pseudo-second-order kinetics. Adsorption of arsenic (V) was greatest at
pH 2, while adsorption at pH 7-9 was within 91% of maximum adsorption, whereas
adsorption decreased to 32% of maximum adsorption at pH 10. Surface charge
analysis confirmed the adsorption of arsenic (V) onto the acidic surface of the
Mn3O4 sorbent with a pHPZC of 7.32. The presence of coexisting ions bicarbonate
and phosphate resulted in a decrease in arsenic (V) uptake. Comparable adsorption
capacities were obtained for the synthetic solution and both groundwater samples.
Overall, crystalline Mn3O4 was an effective and viable sorbent for removal of
arsenic (V) from natural water, removing greater than 95% of arsenic (V) from a 1
mg L(-1) solution within 60 min of contact time.
PMID- 25137535
TI - Kinetic study of adsorption of arsenic onto New Zealand Ironsand (NZIS).
AB - New Zealand Ironsand (NZIS), an iron-rich sand ubiquitous to the coast of the
North Island of New Zealand was examined for the removal of arsenic (both As
(III) and As (V)) by adsorption. Batch experiments were performed to evaluate the
adsorption kinetics at three different pH conditions (3.0, 7.5 and 11.0). In
addition, a column test was conducted to obtain the breakthrough curve and
appraise the arsenic removal capacity of NZIS used as a filter media. The kinetic
study showed that a very long contact time (>144 h) was needed to reach
equilibrium and the nature of the adsorption was well described (R(2) value more
than 0.96 at each pH condition) with a pseudo-second-order adsorption kinetic
model for both As (III) and As (V). In column tests, a pore volume (PV) of 700
and 400 yielded a total arsenic level less than the WHO guideline value of 10
MUg/L for As (III) and As (V), respectively.
PMID- 25137536
TI - Characterization of arsenite-oxidizing bacteria isolated from arsenic
contaminated groundwater of West Bengal.
AB - Nine arsenic (As)-resistant bacterial strains isolated from As-rich groundwater
samples of West Bengal were characterized to elucidate their potential in
geomicrobial transformation and bioremediation aspects. The 16S rRNA gene-based
phylogenetic analysis revealed that the strains were affiliated with genera
Actinobacteria, Microbacterium, Pseudomonas and Rhizobium. The strains exhibited
high resistance to As [Minimum inhibitory concentration (MIC) >= 10 mM As(3+) and
MIC >= 450 mM As(5+)] and other heavy metals, e.g., Cu(2+), Cr(2+), Ni(2+), etc.
(MIC >= 2 mM) as well as As transformation (As(3+) oxidation and As(5+)
reduction) capabilities. Their ability to utilize diverse carbon source(s)
including hydrocarbons and different alternative electron acceptor(s) (As(5+),
SO4(2-), S2O3(2-), etc.) during anaerobic growth was noted. Growth at wide range
of pH, temperature and salinity, production of siderophore and biofilm were
observed. Together with these, growth pattern and transformation kinetics
indicated a high As(3+) oxidation activity of the isolates Rhizobium sp. CAS934i,
Microbacterium sp. CAS905i and Pseudomonas sp. CAS912i. A positive relation
between high As(3+) resistance and As(3+) oxidation and the supportive role of
As(3+) in bacterial growth was noted. The results highlighted As(3+) oxidation
process and metabolic repertory of strains indigenous to contaminated groundwater
and indicates their potential in As(3+) detoxification. Thus, such metabolically
well equipped bacterial strains with highest As(3+) oxidation activities may be
used for bioremediation of As contaminated water and effluents in the near
future.
PMID- 25137537
TI - Variation in composition and relative content of accumulated photopigments in a
newly isolated Rhodobacter capsulatus strain XJ-1 in response to arsenic.
AB - This study aimed to isolate and characterize a new arsenic (As)-tolerant
bacterial strain (XJ-1) from the Halosol soil, to evaluate its As tolerance, and
to examine the variation in composition and relative content of accumulated
photosynthetic pigments in response to As. The experiments were performed with
high-performance liquid chromatography (HPLC), inductively-coupled plasma mass
spectrometry (ICP-MS), liquid chromatography/mass spectrometry (LC/MS), thin
layer chromatography (TLC) and grayscale intensity image analysis using Gel-Pro
analyzer software. Strain XJ-1 was identified as Rhodobacter (R.) capsulatus
based on 16S rRNA gene sequencing and physiological characteristics. Strain XJ-1
was able to grow when exposed to arsenite [As(III)] and arsenate [As(V)] under
anaerobic-light conditions. The median effective concentrations (EC50) of As(III)
and As(V) were 0.61 mM and 2.03 mM, respectively. Strain XJ-1 could reduce As(V)
to As(III), but As(III) could not be transformed back to As(V) or other organic
As compounds. Accumulation of bacteriochlorophylls and carotenoids in strain XJ-1
varied in the presence of 0.2-1.2 mM As(III) and 0-2.5 mM As(V). As exposure
resulted in pronounced variation in compositions and contents of photosynthetic
pigments, especially hydroxyspheroidene, bacteriophaeophytin, the ratio of
tetrahydrogeranylgeranyl to phytylated BChl a, and the ratio of spheroidene to
spheroidenone. This research highlights the adaptative response of R. capsulatus
strain XJ-1 photosystems to environmental As, and demonstrates the potential of
utilizing the sensitivity of its photosynthetic pigments to As(III) and As(V) for
the biodetection of As in the environment.
PMID- 25137538
TI - Amperometric determination of cadmium, lead, and mercury metal ions using a novel
polymer immobilised horseradish peroxidase biosensor system.
AB - This work was undertaken to develop a novel Pt/PANI-co-PDTDA/HRP biosensor system
for environmental applications to investigate the inhibition studies by specific
heavy metals, to provide data suitable for kinetic studies and further
application of the biosensor to environmental samples. The newly constructed
biosensor was compared to the data of the well-researched Pt/PANI/HRP biosensor.
Optimised experimental conditions, such as the working pH for the biosensor was
evaluated. The functionality of the amperometric enzyme sensor system was
demonstrated by measuring the oxidation current of hydrogen peroxide followed by
the development of an assay for determination of metal concentration in the
presence of selected metal ions of Cd(2+), Pb(2+) and Hg(2+). The detection
limits were found to be 8 * 10(-4) MUg L(-1) for cadmium, 9.38 * 10(-4) MUg L(-1)
for lead and 7.89 * 10(-4) MUg L(-1) for mercury. The World Health Organisation
recommended that the maximum safety level of these metals should not exceed 0.005
mg L(-1) of Cd(2+), 0.01 mg L(-1) of Pb(2+) and 0.001 mg L(-1) of Hg(2+.),
respectively. The analytical and detection data for the metals investigated were
observed to be lower than concentrations recommended by several bodies including
World Health Organisation and Environmental Protection Agencies. Therefore the
biosensors developed in this study can be used to screen the presence of these
metals in water samples because of its low detection limit. The modes of
inhibition of horseradish peroxidase by Pb(2+), Cd(2+) and Hg(2+) as analysed
using the double reciprocal plots of the Michaelis-Menten equation was found to
be reversible and uncompetitive inhibition. Based on the Km(app) and Imax values
for both biosensors the results have shown smaller values. These results also
proved that the enzyme modified electrode is valuable and can be deployed for the
determination or screening of heavy metals.
PMID- 25137540
TI - Strategies of management for the whole treatment of leachates generated in a
landfill and in a composting plant.
AB - This study compares the leachates generated in the treatment of Municipal Solid
Wastes (MSW) of similar origin but managed in two different ways: (a) sorting and
composting in a Treatment Plant in Aranda de Duero (Burgos, Spain), and (b)
direct dumping in a landfill in Aranda de Duero (Burgos, Spain) with no prior
treatment. Two different leachates were considered for the former: those
generated in the fermentation shed (P1) and those generated in the composting
tunnels (P2); another leachate was collected from the landfill (P3). Physical and
chemical properties, including heavy metal contents, were seasonally monitored in
the different leachates. This study allowed us to conclude that the sampling
season had a significant effect on Pb, Cd, Ni, Mg and total-N contents (P <
0.01). Similarly, leachates P1, P2 and P3 exhibited significant overall
differences for most of the measured parameters except for Cd, Cu, Pb, K, Fe, C
inorg and C-org contents (P < 0.01). This study concludes with the feasibility of
a whole treatment for both leachates using ultrafiltration in a membrane
bioreactor (MBR).
PMID- 25137539
TI - Removal of dicyclohexyl acetic acid from aqueous solution using ultrasound, ozone
and their combination.
AB - Naphthenic acids are a complex mixture of organic components, some of which
include saturated alkyl-substituted cycloaliphatic carboxylic acids and acyclic
aliphatic acids. They are naturally found in hydrocarbon deposits like oil sand,
petroleum, bitumen and crude oil. In this study, the oxidation of a relatively
high molecular weight naphthenic acid (Dicyclohexyl acetic acid) was investigated
using ozonation, ultrasonication and hydrogen peroxide alone and their
combinations. Effects on oxidation of dicyclohexyl acetic acid (DAA) were
measured for different concentrations of ozone ranging between 0.7 to 3.3 mg L(
1) and pH in the range 6 to 10. Ultrasonication and hydrogen peroxide alone were
not effective to oxidize dicyclohexyl acetic acid, but combining ultrasonication
with H2O2 had a significant effect on oxidation of dicyclohexyl acetic acid with
maximum removal reaching to 84 +/- 2.2% with 81 +/- 2.1% reduction in chemical
oxygen demand (COD). Synergistic effects were observed for combining
ultrasonication with ozonation and resulted in 100% DAA removal with 98 +/- 0.8%
reduction in COD within 15 min at 3.3 mg L(-1) ozone concentration and 130 Watts
ultrasonication power. The reaction conditions obtained for the maximum oxidation
of DAA and COD removal were used for the degradation of naphthenic acids mixture
extracted from oil sands process water (OSPW). The percentage oxidation of NAs
mixture extracted from OSPW was 89.3 +/- 1.1% in ozonation and combined ozonation
and ultrasonication, but COD removal observed was 65 +/- 1.2% and 78 +/- 1.4% for
ozonation and combined ozonation and ultrasonication treatments, respectively.
PMID- 25137541
TI - Cosmetic wastewater treatment using the Fenton, Photo-Fenton and H2O2/UV
processes.
AB - Advanced Oxidation Processes (AOPs), such as the Fenton, photo-Fenton and H2O2/UV
processes, have been investigated for the treatment of cosmetic wastewaters that
were previously coagulated by FeCl3. The Photo-Fenton process at pH 3.0 with
1000/100 mg L(-1) H2O2/Fe(2+) was the most effective (74.0% Chemical Oxygen
Demand (COD) removal). The Fenton process with 1200/500 mg L(-1) H2O2/Fe(2+)
achieved a COD removal of 72.0%, and the H2O2/UV process achieved a COD removal
of 47.0%. Spreading the H2O2 doses over time to obtain optimal conditions did not
improve COD removal. The kinetics of the Fenton and photo-Fenton processes may be
described by the following equation: d[COD]/dt = -a[COD] t(m) (t represents time
and a and m are constants). The rate of COD removal by the H2O2/UV process may be
described by a second-order reaction equation. Head Space, Solid-Phase
MicroExtraction, Gas Chromatography and Mass Spectrometry (HS-SPME-GC-MS) were
used to identify 48 substances in precoagulated wastewater. Among these
substances, 26 were fragrances. Under optimal AOP conditions, over 99% of the
identified substances were removed in 120 min.
PMID- 25137542
TI - Influence of parameters on the photocatalytic degradation of phenolic
contaminants in wastewater using TiO2/UV system.
AB - The photocatalytic degradation of phenol in aqueous suspension using commercial
TiO2 powder (Degussa P-25) irradiated with UV light was investigated.
Photodegradation was compared using a photocatalyst (TiO2 alone), direct
photolysis (UV alone) and TiO2/UV in a single batch reactor with mercury lamp
irradiation. The study focused on the influence of various operating parameters
on phenol treatment efficiency, including catalyst dosage, initial concentration
of phenol, temperature, pH and change in pH were systematically investigated. The
highest phenol degradation rate was obtained at pH 9.0, temperature 60 degrees C
and catalyst dose of 2 g L(-1) with higher mineralization efficiency (in terms of
TOC reduction). Experimental results showed that under optimized conditions the
phenol removal efficiency was 98% and 100% for the TiO2/UV and TiO2/UV/H2O2
system, respectively. No significant effect on addition of chloride and metal
ions was observed. Photodegradation of phenol followed first-order kinetics. To
test whether the phenol removal was possible for wastewater using a TiO2/UV
system, the degradation study was conducted with the real obtained wastewater.
The removal of phenol from obtained wastewater and the synthetic wastewater
containing phenol was comparable. The TiO2/UV system developed here is expected
to be useful for the treatment of wastewater containing phenol.
PMID- 25137543
TI - Comparison of five wastewater COD fractionation methods for dynamic simulation of
MBR systems.
AB - Five different wastewater COD fractionation methods were employed for simulating
an experimental MBR wastewater treatment plant using WEST. The predictions of
dynamic simulations using as input the data obtained according to each influent
characterization methodology were compared with the results of the experimental
system and differences between experimental and predicted values were analyzed in
order to select the fractionation method which provides the best fitting and
minimizes errors. Three of these methods were based on the determination of the
biodegradable fractions using respirometric assays of real wastewater filtered
through 0.45- and 0.22-MUm pore size filters or adding a previous flocculation
step before filtration. Moreover, a method based on physicochemical analyses and
another one based on theoretical coefficients were also compared. Simulated
system performance and effluent quality greatly depended upon the influent
characterization and the proper model calibration. Thus the importance of
selecting a suitable fractionation methodology is high, especially in MBR systems
working at specific operational conditions that may alter COD fractions. In this
study, MLSS in the bioreactors and sludge supernatant COD concentrations were
better predicted when the influent characterization was based on respirometric
methods. Both the method based on theoretical coefficients and the
physicochemical method underestimated the particulate inert fraction and
therefore, also the MLSS concentrations. Moreover, these results showed that for
a correct effluent COD prediction in MBR systems, it is necessary to take into
account that the membrane retained part of the soluble inert fraction.
PMID- 25137544
TI - An integrated use of multiple biomarkers to investigate the individual and
combined effect of copper and cadmium on the marine green mussel (Perna viridis).
AB - The present study documents individual and combined sub-lethal effect of one
redox active (copper) and one non-redox active (cadmium) metal on green mussel
(Perna viridis). The mussels were exposed to 60 MUg L(-1) of Cu and 150 MUg L(-1)
of Cd (individually and in combination) for 21 days. Histopathological and
ultrastructural studies revealed significant metal induced alterations such as
vacuolization, fusion of gill lamellae, enhance mucous deposition, hyperplasia
and necrosis in gills. Antioxidant enzyme assays revealed significant increase in
superoxide dismutase (SOD), glutathione S-transferase (GST) and glutathione
peroxidase (GPx) activity. Similarly, single exposure to Cd and Cu caused
significant induction in Malate dehydrogenase (MDH) activity. However, combined
Cu+Cd exposure modulated suppression in MDH activity. Unlike MDH, Cu and Cd
individual exposure resulted in a decrease in esterase (EST) activity, but their
combined exposure caused an induction. Non-enzymatic biomarkers such as lipid
peroxidation (LPO) and metallothionein (MT) levels showed no significant change
in response to Cu exposure, whereas, individual Cd exposure or Cd exposure in
combination with Cu caused significant changes in their levels. Comet assay
revealed a significant increase in DNA damage upon metal exposure. These results
indicate that Cu (redox active) and Cd (non-redox active) can induce measurable
physiological, biochemical as well as genotoxic perturbations in mussels even at
sub-lethal concentrations. A monitoring programme based on the biomarkers
discussed here would be useful to study the effect of metal pollutants reaching
the coastal waters.
PMID- 25137545
TI - Efficacy of hair analysis for monitoring exposure to uranium: a mini-review.
AB - In spite of the ease with which samples may be collected and the stability of the
samples after collection, the use of hair mineral analysis for monitoring
environmental exposures and evaluating heavy metal poisonings has remained
controversial since its initial applications for these purposes in the early
1950s. Among the major arguments against using hair mineral analysis in general
were the absence of biokinetic models and/or metabolic data that adequately
described the incorporation of trace elements into the hair, the absence of
correlations between the concentrations of trace elements in the hair and their
concentrations in other tissues, the inability to distinguish between trace
elements that were deposited in the hair endogenously and those that were
deposited on the hair exogenously, the absence of reliable reference ranges for
interpreting the results of hair mineral analysis and a lack of standard
procedures for the collecting, preparing and analyzing the hair samples. The
developments of the past two decades addressing these objections are reviewed
here, and arguments supporting the use of hair analysis for monitoring
environmental and/or occupational exposures to uranium are made on the basis of
the information presented in this review.
PMID- 25137546
TI - Ecotoxicity of silver nanomaterials in the aquatic environment: a review of
literature and gaps in nano-toxicological research.
AB - There has been extensive growth in nanoscale technology in the last few decades
to such a degree that nanomaterials (NMs) have become a constituent in a wide
range of commercial and domestic products. With NMs already in use in several
consumer products, concerns have emerged regarding their potential adverse
environmental impacts. Although research has been undertaken in order to minimise
the gaps in our understanding of NMs in the environment, little is known about
their bioavailability and toxicity in the aquatic environment. Nano-toxicology is
defined as the study of the toxicity of nanomaterials. Nano-toxicology studies
remain poorly and unevenly distributed. To date most of the research undertaken
has been restricted to a narrow range of test species such as daphnids. Crabs are
bio-indicators that can be used for toxicological research on NMs since they
occupy a significant position in the aquatic food chain. In addition, they are
often used in conventional ecotoxicological studies due to their high sensitivity
to environmental stressors and are abundantly available. Because they are benthic
organisms they are prone to contaminant uptake and bioaccumulation. To our
knowledge the crab has never been used in nano-toxicological studies. In this
context, an extensive review on published scientific literature on the
ecotoxicity of silver NPs (AgNPs) on aquatic organisms was conducted. Some of the
most common biomarkers used in ecotoxicological studies are described. Emphasis
is placed on the use of biomarker responses in crabs as monitoring tools, as well
as on its limitations. Additionally, the gaps in nano-toxicological research and
recommendations for future research initiatives are addressed.
PMID- 25137547
TI - Method to simultaneously determine the sphingosine 1-phosphate breakdown product
(2E)-hexadecenal and its fatty acid derivatives using isotope-dilution HPLC
electrospray ionization-quadrupole/time-of-flight mass spectrometry.
AB - Sphingosine 1-phosphate (S1P), a bioactive lipid involved in various
physiological processes, can be irreversibly degraded by the membrane-bound S1P
lyase (S1PL) yielding (2E)-hexadecenal and phosphoethanolamine. It is discussed
that (2E)-hexadecenal is further oxidized to (2E)-hexadecenoic acid by the long
chain fatty aldehyde dehydrogenase ALDH3A2 (also known as FALDH) prior to
activation via coupling to coenzyme A (CoA). Inhibition or defects in these
enzymes, S1PL or FALDH, result in severe immunological disorders or the Sjogren
Larsson syndrome, respectively. Hence, it is of enormous importance to
simultaneously determine the S1P breakdown product (2E)-hexadecenal and its fatty
acid metabolites in biological samples. However, no method is available so far.
Here, we present a sensitive and selective isotope-dilution high performance
liquid chromatography-electrospray ionization-quadrupole/time-of-flight mass
spectrometry method for simultaneous quantification of (2E)-hexadecenal and its
fatty acid metabolites following derivatization with 2-diphenylacetyl-1,3
indandione-1-hydrazone and 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide.
Optimized conditions for sample derivatization, chromatographic separation, and
MS/MS detection are presented as well as an extensive method validation. Finally,
our method was successfully applied to biological samples. We found that (2E)
hexadecenal is almost quantitatively oxidized to (2E)-hexadecenoic acid, that is
further activated as verified by cotreatment of HepG2 cell lysates with (2E)
hexadecenal and the acyl-CoA synthetase inhibitor triacsin C. Moreover,
incubations of cell lysates with deuterated (2E)-hexadecenal revealed that no
hexadecanoic acid is formed from the aldehyde. Thus, our method provides new
insights into the sphingolipid metabolism and will be useful to investigate
diseases known for abnormalities in long-chain fatty acid metabolism, e.g., the
Sjogren-Larsson syndrome, in more detail.
PMID- 25137548
TI - A Novel SHOC2 Variant in Rasopathy.
AB - Rasopathies are a group of genetic disorders caused by germline mutations in
multiple genes of the Extracellular signal-Regulated Kinases 1 and 2 (ERK1/2)
pathway. The only previously identified missense mutation in SHOC2, a scaffold
protein of the ERK1/2 pathway, led to Noonan-like syndrome with loose anagen
hair. Here, we report a novel mutation in SHOC2(c.519G>A; p.M173I) that leads to
a Rasopathy with clinical features partially overlapping those occurring in
Noonan and cardiofaciocutaneous syndromes. Studies to clarify the significance of
this SHOC2 variant revealed that the mutant protein has impaired capacity to
interact with protein phosphatase 1c (PP1c), leading to insufficient activation
of RAF-1 kinase. This SHOC2 variant thus is unable to fully rescue ERK1/2
activity in cells depleted of endogenous SHOC2. We conclude that SHOC2 mutations
can cause a spectrum of Rasopathy phenotypes in heterozygous individuals.
Importantly, our work suggests that individuals with mild Rasopathy symptoms may
be underdiagnosed.
PMID- 25137549
TI - Discovery of carbohybrid-based 2-aminopyrimidine analogues as a new class of
rapid-acting antimalarial agents using image-based cytological profiling assay.
AB - New antimalarial agents that exhibit multistage activities against drug-resistant
strains of malaria parasites represent good starting points for developing next
generation antimalarial therapies. To facilitate the progression of such agents
into the development phase, we developed an image-based parasitological screening
method for defining drug effects on different asexual life cycle stages of
Plasmodium falciparum. High-throughput screening of a newly assembled diversity
oriented synthetic library using this approach led to the identification of
carbohybrid-based 2-aminopyrimidine compounds with fast-acting growth inhibitory
activities against three laboratory strains of multidrug-resistant P. falciparum.
Our structure-activity relationship study led to the identification of two
derivatives (8aA and 11aA) as the most promising antimalarial candidates (mean
EC50 of 0.130 and 0.096 MUM against all three P. falciparum strains, selectivity
indices >600, microsomal stabilities >80%, and mouse malaria ED50 values of 0.32
and 0.12 mg/kg/day, respectively), targeting all major blood stages of multidrug
resistant P. falciparum parasites.
PMID- 25137550
TI - RBC transfusion in pediatric patients supported with extracorporeal membrane
oxygenation: is there an impact on tissue oxygenation?
AB - OBJECTIVE: To examine first the RBC transfusion practice in pediatric patients
supported with extracorporeal membrane oxygenation and second the relationship
between transfusion of RBCs and changes in mixed venous saturation (SvO2) and
cerebral regional tissue oxygenation, as measured by near-infrared spectroscopy
in patients supported with extracorporeal membrane oxygenation. DESIGN:
Retrospective observational study. SETTING: Pediatric, cardiovascular, and
neonatal ICUs of a tertiary care children's hospital. PATIENTS: All pediatric
patients supported with extracorporeal membrane oxygenation between January 1,
2010, and December 31, 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
There were 45 patients supported with extracorporeal membrane oxygenation. The
median (interquartile range) phlebotomy during extracorporeal membrane
oxygenation was 75 mL/kg (33, 149 mL/kg). A total of 617 transfusions were
administered (median, 9 per patient; range = 1-57). RBC volumes transfused during
extracorporeal membrane oxygenation support were 254 mL/kg (136, 557) and 267
mL/kg (187, 393; p = 0.82) for cardiac and noncardiac patients, respectively.
Subtracting the volume of RBCs used for extracorporeal membrane oxygenation
circuit priming, median RBC transfusion volumes were 131 and 80 mL/kg for cardiac
and noncardiac patients, respectively (p = 0.26). The cardiac surgical patients
received the most RBCs (529 vs 74 mL/kg for nonsurgical cardiac patients). The
median hematocrit maintained during extracorporeal membrane oxygenation support
was 37%, with no difference between cardiac and noncardiac patients. Patients
supported with extracorporeal membrane oxygenation were exposed to a median of
10.9 (range, 3-43) individual donor RBC units. Most transfusions resulted in no
significant change in either SvO2 or cerebral near-infrared spectroscopy. Only 5%
of transfusions administered (31/617) resulted in an increase in SvO2 of more
than 5%, whereas an increase in cerebral near-infrared spectroscopy of more than
5 was only observed in 9% of transfusions (53/617). Most transfusions (73%) were
administered at a time when the pretransfusion SvO2 was more than 70%.
CONCLUSIONS: Patients supported with extracorporeal membrane oxygenation were
exposed to large RBC transfusion volumes for treatment of mild anemia resulting
from blood loss, particularly phlebotomy. In the majority of events, RBC
transfusion did not significantly alter global tissue oxygenation, as assessed by
changes in SvO2 and cerebral near-infrared spectroscopy. Most transfusions were
administered at a time at which the patient did not appear to be oxygen delivery
dependent according to global measures of tissue oxygenation.
PMID- 25137552
TI - Time to reappraise the use of body mass index in genetic association studies of
children?
PMID- 25137551
TI - Greater fluctuations in serum sodium levels are associated with increased
mortality in children with externalized ventriculostomy drains in a PICU.
AB - OBJECTIVES: Dysnatremia is common in critically ill children due to disruption of
hormonal homeostasis. Children with brain injury are at risk for syndrome of
inappropriate antidiuretic hormone, cerebral salt wasting, and sodium losses due
to externalized ventricular drain placement. We hypothesized that among PICU
patients managed with an externalized ventricular drain, hyponatremia is common,
hyponatremia is associated with seizures and in-hospital mortality, and greater
sodium fluctuations are associated with in-hospital mortality. DESIGN:
Retrospective observational study. SETTING: Tertiary care PICU. PATIENTS: All
pediatric patients treated in the PICU with an externalized ventricular drain
from January 2005 to December 2009. Patients were identified by searching the
physician order entry database for externalized ventricular drain orders.
Hyponatremia was defined as the minimum sodium during patients' externalized
ventricular drain time and was categorized as mild (131-134 mEq/L) or moderate to
severe (<= 130 mEq/L). Magnitude of sodium fluctuation was defined as the
difference between a patient's highest and lowest sodium during the time in which
an externalized ventricular drain was in use (up to 14 d). Seizure was defined as
a clinically evident convulsion during externalized ventricular drain presence. A
priori confounders were age, history of epilepsy, and externalized ventricular
drain indication. Multivariable regression was performed to test the association
between sodium derangements and outcomes. INTERVENTIONS: None. MEASUREMENTS AND
MAIN RESULTS: Three hundred eighty patients were eligible. One hundred nine (29%)
had mild hyponatremia, and 30 (8%) had moderate to severe hyponatremia. Twenty
eight patients (7%) had a seizure while hospitalized. Eighteen patients died (5%)
prior to discharge. Survivors had a median daily sodium fluctuation of 1 mEq/L [0
5] vs non-survivors 9 mEq/L [6-11] (p < 0.001) and a median sodium fluctuation of
5 mEq/L [2-8] vs non-survivors 15 mEq/L [9-24] (p < 0.001) during externalized
ventricular drain management. After controlling for a priori covariates and
potential confounders, hyponatremia was not associated with an increased odds of
seizures or in-hospital mortality. However, greater fluctuations in daily sodium
(odds ratio, 1.38; 95% CI, 1.06-1.8) and greater fluctuations in sodium during
externalized ventricular drain management were associated with increased odds of
in-hospital mortality (odds ratio, 1.59; 95% CI, 1.2-2.11). CONCLUSIONS:
Hyponatremia was common in PICU patients treated with externalized ventricular
drains but not associated with seizures or in-hospital mortality. Greater sodium
fluctuations during externalized ventricular drain management were independently
associated with increased odds of in-hospital mortality.
PMID- 25137553
TI - Improving the oral health of residents with intellectual and developmental
disabilities: an oral health strategy and pilot study.
AB - This article presents an oral health (OH) strategy and pilot study focusing on
individuals with intellectual and/or developmental disabilities (IDD) living in
group homes. The strategy consists of four components: (1) planned action in the
form of the behavioral contract and caregiver OH action planning; (2) capacity
building through didactic and observation learning training; (3) environmental
adaptations consisting of additional oral heath devices and strategies to create
a calm atmosphere; and (4) reinforcement by post-training coaching. A pilot study
was conducted consisting of pre- and post-assessment data collected 1 week before
and 1 week after implementing a 1-month OH strategy. The study sample comprised
11 group homes with 21 caregivers and 25 residents with IDD from one service
organization in a Midwestern city. A process evaluation found high-quality
implementation of the OH strategy as measured by dosage, fidelity, and caregiver
reactions to implementing the strategy. Using repeated cross-sectional and
repeated measures analyses, we found statistically significant positive changes
in OH status and oral hygiene practices of residents. Caregiver self-efficacy as
a mechanism of change was not adequately evaluated; however, positive change was
found in some but not all types of caregiver OH support that were assessed.
Lessons learned from implementing the pilot study intervention and evaluation are
discussed, as are the next steps in conducting an efficacy study of the OH
strategy.
PMID- 25137555
TI - Photocontrolled nanoparticle delivery systems for biomedical applications.
AB - "Smart" stimuli-responsive nanomaterials are becoming popular as targeted
delivery systems because they allow the use of internal or external stimuli to
achieve spatial or temporal control over the delivery process. Among the stimuli
that have been used, light is of special interest because it is not only
noninvasive but also controllable both spatially and temporally, thus allowing
unprecedented control over the delivery of bioactive molecules such as nucleic
acids, proteins, drugs, etc. This is particularly advantageous for biomedical
applications where specificity and selectivity are highly desired. Several
strategies have evolved under the umbrella of light based delivery systems and
can be classified into three main groups. The first strategy involves "caging" of
the bioactive molecule using photolabile groups, loading these caged molecules
onto a carrier and then "uncaging" or activating them at the targeted site upon
irradiation with light of a particular wavelength. The second strategy makes use
of nanocarriers that themselves are made photoresponsive either through
modification with photosensitive groups or through the attachment of photolinkers
on the carrier surface. These nanoparticles upon irradiation dissociate,
releasing the cargo encapsulated within, or the photolinkers attaching the cargo
to the surface get cleaved, resulting in release. The third approach makes use of
the surface plasmon resonance of noble metal based nanoparticles. Upon
irradiation with light at the plasmon resonant frequency, the resulting thermal
or nonthermal field enhancement effects facilitate the release of bioactive
molecules loaded onto the nanoparticles. In addition, other materials, certain
metal sulfides, graphene oxide, etc., also exhibit photothermal transduction that
can be exploited for targeted delivery. These approaches, though effective, are
constrained by their predominant use of UV or visible light to which most
photolabile groups are sensitive. Near infrared (NIR) excitation is preferred
because NIR light is safer and can penetrate deeper in biological tissues.
However, most photolabile groups cannot be excited by NIR light directly. So
light conversion from NIR to UV/visible is required. Nanomaterials that display
upconversion or two-photon-excitation properties have been developed that can
serve as nanotransducers, converting NIR to UV/visible light to which the
aforementioned photoresponsive moieties are sensitive. This Account will review
the existing light-based nanoparticle delivery systems, their applications, the
limitations they face, and the technologies that have emerged in an effort to
overcome these limitations.
PMID- 25137554
TI - Plasmonic library based on substrate-supported gradiential plasmonic arrays.
AB - We present a versatile approach to produce macroscopic, substrate-supported
arrays of plasmonic nanoparticles with well-defined interparticle spacing and a
continuous particle size gradient. The arrays thus present a "plasmonic library"
of locally noncoupling plasmonic particles of different sizes, which can serve as
a platform for future combinatorial screening of size effects. The structures
were prepared by substrate assembly of gold-core/poly(N-isopropylacrylamide)
shell particles and subsequent post-modification. Coupling of the localized
surface plasmon resonance (LSPR) could be avoided since the polymer shell
separates the encapsulated gold cores. To produce a particle array with a broad
range of well-defined but laterally distinguishable particle sizes, the substrate
was dip-coated in a growth solution, which resulted in an overgrowth of the gold
cores controlled by the local exposure time. The kinetics was quantitatively
analyzed and found to be diffusion rate controlled, allowing for precise tuning
of particle size by adjusting the withdrawal speed. We determined the kinetics of
the overgrowth process, investigated the LSPRs along the gradient by UV-vis
extinction spectroscopy, and compared the spectroscopic results to the
predictions from Mie theory, indicating the absence of local interparticle
coupling. We finally discuss potential applications of these substrate-supported
plasmonic particle libraries and perspectives toward extending the concept from
size to composition variation and screening of plasmonic coupling effects.
PMID- 25137557
TI - Analyzing and grading effectiveness research: a new approach.
PMID- 25137556
TI - Association between ambient noise exposure, hearing acuity, and risk of acute
occupational injury.
AB - OBJECTIVE: This study aimed to examine the associations between acute workplace
injury risk, ambient noise exposure, and hearing acuity, adjusting for reported
hearing protection use. METHODS: In a cohort of 9220 aluminum manufacturing
workers studied over six years (33 300 person-years, 13 323 person-jobs),
multivariate mixed effects models were used to estimate relative risk (RR) of all
injuries as well as serious injuries by noise exposure category and hearing
threshold level (HTL) adjusting for recognized and potential confounders.
RESULTS: Compared to noise <82 dBA, higher exposure was associated with elevated
risk in a monotonic and statistically significant exposure-response pattern for
all injuries and serious injuries with higher risk estimates observed for serious
injuries [82-84.99 dBA: RR 1.26, 95% confidence interval (95% CI) 0.96-1.64; 85
87.99 dBA: RR 1.39, 95% CI 1.05-1.85; >=88 dBA: RR 2.29, 95% CI 1.52-3.47].
Hearing loss was associated with increased risk for all injuries, but was not a
significant predictor of risk for the subset of more serious injuries. Compared
to those without hearing loss, workers with HTL >=25 dB had 21% increased all
injury risk (RR 1.21, 95% CI 1.09-1.33) while those with HTL 10-24.99 dB had 6%
increased risk (RR 1.06, 95% CI 1.00-1.13). Reported hearing protection type did
not predict injury risk. CONCLUSION: Noise exposure levels as low as 85 dBA may
increase workplace injury risk. HTL was associated with increased risk for all,
but not the subset of serious, injuries. Additional study is needed both to
confirm the observed associations and explore causal pathways.
PMID- 25137558
TI - Transplantation: recognizing self versus non-self: new territory for monocytes.
PMID- 25137561
TI - Development: Wnt5a implicated in CAKUT.
PMID- 25137565
TI - Effect of calcium-ozone treatment on chemical and biological properties of
polyethylene terephthalate.
AB - Ozone (O3 ) treatment of polyethylene terephthalate (PET) in distilled water was
performed in the presence and absence of calcium (Ca(2+) ). PET was oxidized and
thus carboxylic and hydroxyl functional groups were introduced on its surface
after O3 treatment, regardless of the presence or absence of Ca(2+) . In the case
of O3 treatment with Ca(2+) , PET surface was modified with Ca(2+) . Ca(2+)
immobilization was confirmed by X-ray photoelectron spectrometric analysis.
Hydrophilicity was investigated by measuring contact angles (CA). CA of PET
decreased significantly after ozonation. Surface topography of PET before and
after ozone treatment was observed by scanning electron microscopy, and showed no
morphological changes. In vitro studies showed enhanced rat bone marrow cell
responses on the O3 -treated PET surface. Ca(2+) -O3 oxidation at 37 degrees C
for 6 h is expected to be an effective method to fabricate PET with good
biocompatibility.
PMID- 25137566
TI - Study of the kinetics and mechanism of rapid self-assembly in block copolymer
thin films during solvo-microwave annealing.
AB - Microwave annealing is an emerging technique for achieving ordered patterns of
block copolymer films on substrates. Little is understood about the mechanisms of
microphase separation during the microwave annealing process and how it promotes
the microphase separation of the blocks. Here, we use controlled power microwave
irradiation in the presence of tetrahydrofuran (THF) solvent, to achieve lateral
microphase separation in high-chi lamellar-forming poly(styrene-b-lactic acid) PS
b-PLA. A highly ordered line pattern was formed within seconds on silicon,
germanium and silicon on insulator (SOI) substrates. In-situ temperature
measurement of the silicon substrate coupled to condition changes during "solvo
microwave" annealing allowed understanding of the processes to be attained. Our
results suggest that the substrate has little effect on the ordering process and
is essentially microwave transparent but rather, it is direct heating of the
polar THF molecules that causes microphase separation. It is postulated that the
rapid interaction of THF with microwaves and the resultant temperature increase
to 55 degrees C within seconds causes an increase of the vapor pressure of the
solvent from 19.8 to 70 kPa. This enriched vapor environment increases the
plasticity of both PS and PLA chains and leads to the fast self-assembly
kinetics. Comparing the patterns formed on silicon, germanium and silicon on
insulator (SOI) and also an in situ temperature measurement of silicon in the
oven confirms the significance of the solvent over the role of substrate heating
during "solvo-microwave" annealing. Besides the short annealing time which has
technological importance, the coherence length is on a micron scale and dewetting
is not observed after annealing. The etched pattern (PLA was removed by an Ar/O2
reactive ion etch) was transferred to the underlying silicon substrate
fabricating sub-20 nm silicon nanowires over large areas demonstrating that the
morphology is consistent both across and through the film.
PMID- 25137567
TI - A fluorescent biosensor based on carbon dots-labeled oligodeoxyribonucleotide and
graphene oxide for mercury (II) detection.
AB - As the newest two members of the carbon materials family, carbon dots (CDs) and
graphene oxide (GO) possess many excellent optical properties resulting in a wide
range of applications. In this work, we successfully synthesized CDs with a high
quantum-yield, and labeled them on oligodeoxyribonucleotide (ODN). The
fluorescence of resultant CDs-labeled oligodeoxyribonucleotide (ODN-CDs) was
quenched by GO via fluorescence resonance energy transfer. In the presence of
Hg(2+), the fluorescence was recovered by the release of ODN-CDs from GO due to
the formation of T-Hg(2+)-T duplex. In the light of this theory, we designed a
simple, highly sensitive and selective fluorometric Hg(2+) sensor based on CDs
labeled oligodeoxyribonucleotide and GO without complicated, costly and time
consuming operations. Under the optimal conditions, a linear relationship was
obtained between relative fluorescence intensity and the concentration of Hg(2+)
in the range of 5-200 nM (R(2)=0.974). The present GO-based sensor system is
highly selective toward Hg(2+) over a wide range of metal ions and has a
detection limit of 2.6 nM. This method is reliable, and has been successfully
applied for the detection of Hg(2+) in practical samples.
PMID- 25137568
TI - "That one makes things small": Experimentally induced spontaneous memories in 3.5
year-olds.
AB - We introduce a new method for examining spontaneous (unprompted) autobiographical
memories in 3.5-year-old children, by inducing them in a laboratory setting.
Thirty-eight 3.5-year-olds, who had previously participated in a study in our lab
involving highly unique props, were brought back after a one-month delay to the
same lab arranged as in the original study and with the same Experimenter
present. While waiting for the Experimenter in front of the props, their
spontaneous verbalizations about the previous unique experiment were recorded,
scored, and compared to those of 29 naive Controls of the same age. The children
in the experimental group produced significantly more spontaneous verbalizations
related to the to-be-remembered event measured on a variety of dimensions. The
study introduces a promising new approach to investigating spontaneous memories
in young children in a controlled lab setting. The findings are discussed in
relation to involuntary autobiographical memories as examined in adults.
PMID- 25137569
TI - Distorted subjective reports of stimulus onsets under dual-task conditions:
Delayed conscious perception or estimation bias?
AB - We investigated whether selecting a response for one task delays the conscious
perception of another stimulus (delayed conscious perception hypothesis). In two
experiments, participants watched a revolving clock hand while performing two
tasks in close succession (i.e. a dual-task). Two stimuli were presented with
varying stimulus onset asynchrony (SOA). After each trial, participants
separately estimated the onsets of the two stimuli on the clock face. Across two
experiments and four conditions, we manipulated response requirements and
assessed their impact on perceived stimulus onsets. Results showed that (a)
providing speeded responses to the stimuli did lead to greater SOA-dependent
misperceptions of both stimulus onsets as compared to a solely perceptual
condition, and (b) that response grouping reduced these misperceptions. Overall,
the results provide equivocal evidence for the delayed conscious perception
hypothesis. They rather suggest that participants' estimates of the two stimulus
onsets are biased by the interval between their responses.
PMID- 25137562
TI - Translational research in ADPKD: lessons from animal models.
AB - Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in
PKD1 or PKD2, which encode polycystin-1 and polycystin-2, respectively. Rodent
models are available to study the pathogenesis of polycystic kidney disease (PKD)
and for preclinical testing of potential therapies-either genetically engineered
models carrying mutations in Pkd1 or Pkd2 or models of renal cystic disease that
do not have mutations in these genes. The models are characterized by age at
onset of disease, rate of disease progression, the affected nephron segment, the
number of affected nephrons, synchronized or unsynchronized cyst formation and
the extent of fibrosis and inflammation. Mouse models have provided valuable
mechanistic insights into the pathogenesis of PKD; for example, mutated Pkd1 or
Pkd2 cause renal cysts but additional factors are also required, and the rate of
cyst formation is increased in the presence of renal injury. Animal studies have
also revealed complex genetic and functional interactions among various genes and
proteins associated with PKD. Here, we provide an update on the preclinical
models commonly used to study the molecular pathogenesis of ADPKD and test
potential therapeutic strategies. Progress made in understanding the
pathophysiology of human ADPKD through these animal models is also discussed.
PMID- 25137570
TI - Looking at proteins from two dimensions: a review on five decades of 2D
electrophoresis.
AB - Separating proteins according to two different gel-electrophoretic methods not
only increases the resolution power for highly complex samples when compared to
one-dimensional separations, but is also a valuable tool for protein and protein
complex characterization. There are a number of different electrophoresis methods
which can be combined. The combination of isoelectric focusing under denaturing
conditions and SDS polyacrylamide gel electrophoresis delivers the highest
resolution of all bio-analytic techniques. This is a short review on the history
and state of the art of two-dimensional electrophoresis methods, and contains
some practical tips for high resolution 2D electrophoresis, which are based on
several decades of experience with this method.
PMID- 25137572
TI - Singly protonated dehydronorcantharidin silver coordination polymer induces
apoptosis of lung cancer cells via reactive oxygen species-mediated mitochondrial
pathway.
AB - Silver complexes have been shown to possess antimicrobial and anticancer
properties. Ag-SP-DNC, a novel silver and singly protonated dehydronorcantharidin
complex, was synthesized in our previous study. In this study, we offer evidence
that Ag-SP-DNC elicits a reactive oxygen species (ROS)-mediated mitochondrial
apoptosis in lung cancer cells. Ag-SP-DNC inhibited the growth of A549 cells by
inducing G2/M phase cell cycle arrest and apoptosis. Ag-SP-DNC induced apoptosis
was associated with the levels of intracellular ROS. The further study revealed
that Ag-SP-DNC disrupted the mitochondrial membrane potential, induced the
caspase-3 activation and led to the translocation of apoptosis inducing factor
and endonucleaseG to the nucleus. These findings have important implications for
the development of silver complexes for anticancer applications.
PMID- 25137571
TI - Effects of lateral funiculus sparing, spinal lesion level, and gender on recovery
of bladder voiding reflexes and hematuria in rats.
AB - Deficits in bladder function are complications following spinal cord injury
(SCI), severely affecting quality of life. Normal voiding function requires
coordinated contraction of bladder and urethral sphincter muscles dependent upon
intact lumbosacral reflex arcs and integration of descending and ascending spinal
pathways. We previously reported, in electrophysiological recordings, that
segmental reflex circuit neurons in anesthetized male rats were modulated by a
bilateral spino-bulbo-spinal pathway in the mid-thoracic lateral funiculus. In
the present study, behavioral measures of bladder voiding reflexes and hematuria
(hemorrhagic cystitis) were obtained to assess the correlation of plasticity
dependent recovery to the degree of lateral funiculus sparing and mid-thoracic
lesion level. Adult rats received mid-thoracic-level lesions at one of the
following severities: complete spinal transection; bilateral dorsal column
lesion; unilateral hemisection; bilateral dorsal hemisection; a bilateral lesion
of the lateral funiculi and dorsal columns; or a severe contusion. Voiding
function and hematuria were evaluated by determining whether the bladder was
areflexic (requiring manual expression, i.e., "crede maneuver"), reflexive
(voiding initiated by perineal stroking), or "automatic" (spontaneous voiding
without caretaker assistance). Rats with one or both lateral funiculi spared
(i.e., bilateral dorsal column lesion or unilateral hemisection) recovered
significantly faster than animals with bilateral lateral funiculus lesions,
severe contusion, or complete transection. Bladder reflex recovery time was
significantly slower the closer a transection lesion was to T10, suggesting that
proximity to the segmental sensory and sympathetic innervation of the upper
urinary tract (kidney, ureter) should be avoided in the choice of lesion level
for SCI studies of micturition pathways. In addition, hematuria duration was
significantly longer in males, compared to females, despite similar bladder
reflex onset times. We conclude that the sparing of the mid-thoracic lateral
funiculus on one side is required for early recovery of bladder reflex voiding
function and resolution of hematuria.
PMID- 25137573
TI - Pyridine-3-carboxamide-6-yl-ureas as novel inhibitors of bacterial DNA gyrase:
structure based design, synthesis, SAR and antimicrobial activity.
AB - The development of antibacterial drugs based on novel chemotypes is essential to
the future management of serious drug resistant infections. We herein report the
design, synthesis and SAR of a novel series of N-ethylurea inhibitors based on a
pyridine-3-carboxamide scaffold targeting the ATPase sub-unit of DNA gyrase.
Consideration of structural aspects of the GyrB ATPase site has aided the
development of this series resulting in derivatives that demonstrate excellent
enzyme inhibitory activity coupled to potent Gram positive antibacterial
efficacy.
PMID- 25137574
TI - Isolation and cytotoxic effect of anthraquinones from Morinda umbellata.
AB - Four new anthraquinones, 1,6-dihydroxy-2-methoxymethylanthraquinone (1), 6
hydroxy-7-methoxy-2-methoxymethylanthraquinone (3), 3,6-dihydroxy-7-methoxy-2
methylanthraquinone (4), and 6-hydroxy-2-methoxymethylanthraquinone (8), together
with 12 known anthraquinones and 6 other known compounds, were isolated from the
EtOAc extract of Morinda umbellata. Among the isolated compounds, 1, rubiadin
(14), and, 3-hydroxy-2-hydroxymethylanthraquinone (16) exhibited significant
cytotoxicities against HepG2 cells, with GI50 values of 4.4, 3.6, and 4.8 uM,
respectively.
PMID- 25137575
TI - Bioactive sesquiterpene coumarins from Ferula pseudalliacea.
AB - One new and five known sesquiterpene coumarins were isolated from the roots of
Ferula pseudalliacea. The structures were elucidated by 1D and 2D NMR, and HR
ESIMS data as 4'-hydroxy kamolonol acetate (1), kamolonol (2), szowitsiacoumarin
A (3), farnesiferon B (4), farnesiferol C (5), and flabellilobin A (6). The
absolute configuration of compounds 1, 2, and 4 was established by comparison of
experimental and simulated electronic circular dichroism spectra using time
dependence density function theory. 4'-Hydroxy kamolonol acetate and kamolonol
showed antibacterial activity against Heliobacter pylori and Staphylococcus
aureus at a concentration of 64 ug/mL. Kamolonol, 4'-hydroxy kamolonol acetate,
and farnesiferon B displayed a cytotoxic activity in HeLa cells, with an IC50 of
3.8, 4.5, and 7.7 uM, respectively.
PMID- 25137577
TI - Compromise solutions between conservation and road building in the tropics.
AB - Road construction is now common through wilderness and protected areas in
tropical and subtropical countries with adverse consequences for their high
native biodiversity. Here, we summarize the scope of the problem and advance
specific compromise solutions that reconcile development with conservation.
PMID- 25137576
TI - Antioxidative activity of diarylheptanoids from the bark of black alder (Alnus
glutinosa) and their interaction with anticancer drugs.
AB - Diarylheptanoids belong to polyphenols, a group of plant secondary metabolites
with multiple biological properties. Many of them display antioxidative,
cytotoxic, or anticancer actions and are increasingly recognized as potential
therapeutic agents. The aim of this study was to evaluate antioxidant and
cytoprotective activity of two diarylheptanoids: platyphylloside 5(S)-1,7-di(4
hydroxyphenyl)-3-heptanone-5-O-beta-D-glucopyranoside (1) and its newly
discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-beta-D-[6-(E-p
coumaroylglucopyranosyl)]heptane-3-one (2), both isolated from the bark of black
alder (Alnus glutinosa). To that end, we have employed a cancer cell line (NCI
H460), normal human keratinocytes (HaCaT), and peripheral blood mononuclear
cells. The effects on cell growth were assessed by the 3-(4,5-dimethylthiazol-2
yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Cell death was examined
by annexin V/propidium iodide staining on a flow cytometer. Reactive oxygen
species production was examined by dihydroethidium staining. Mitochondrial
structure and doxorubicin localization were visualized by fluorescent microscopy.
Gene expression of manganese superoxide dismutase and hypoxia-inducible factor
1alpha was determined by reverse transcription polymerase chain reaction.
Diarylheptanoids antagonized the effects of either doxorubicin or cisplatin,
significantly increasing their IC50 values in normal cells. Diarylheptanoid 1
induced the retention of doxorubicin in cytoplasm and reduced mitochondrial
fragmentation associated with doxorubicin application. Diarylheptanoid 2 reduced
the reactive oxygen species production induced by cisplatin. Both compounds
increased the messenger ribonucleic acid expression of enzymes involved in
reactive oxygen species elimination (manganese superoxide dismutase and hypoxia
inducible factor-1alpha). These results indicate that neutralization of reactive
oxygen species is an important mechanism of diarylheptanoid action, although
these compounds exert a considerable anticancer effect. Therefore, these
compounds may serve as protectors of normal cells during chemotherapy without
significantly diminishing the effect of the applied chemotherapeutic.
PMID- 25137578
TI - Beaked whales.
PMID- 25137579
TI - piRNAs.
PMID- 25137580
TI - Multisensory context portends object memory.
PMID- 25137581
TI - Touch improvement at the hand transfers to the face.
PMID- 25137582
TI - Embodiment of others' hands elicits arousal responses similar to one's own hands.
PMID- 25137583
TI - Object perception: where do we see the weight?
AB - A new study of the response of the human brain as subjects view objects of
different weights they are about to lift shows that the weight of objects, which
influences the way we act upon them, is represented in the ventral stream of the
visual cortex.
PMID- 25137584
TI - Golgi apparatus: finally mechanics comes to play in the secretory pathway.
AB - New findings report a mechanical role for actin in Golgi organization and
vesicular trafficking. An elegant study uses optical tweezers and live-cell
imaging to demonstrate the effects of a mechanical constraint on the dynamics of
secretory membrane trafficking, combining physical experimental approaches with
in cellulo studies of endomembranes.
PMID- 25137585
TI - Behavioral sequencing: competitive queuing in the fly CNS.
AB - A study of grooming behaviors in Drosophila suggests a neuronal mechanism for how
animals produce complex motor patterns from ordered interactions among modules of
different motor acts. This mechanism may be a common one in many nervous systems.
PMID- 25137586
TI - Multiciliogenesis: multicilin directs transcriptional activation of centriole
formation.
AB - During differentiation of multiciliated cells, numerous centrioles are generated
in each cell to act as templates for the formation of a corresponding number of
cilia. A new study reveals that multicilin, a protein required for
multiciliogenesis, is a key component of a regulatory complex that activates the
transcription of genes required for centriole formation.
PMID- 25137587
TI - Animal behaviour: task differentiation by personality in spider groups.
AB - In social animals, group efficiency is often assumed to increase with task
differentiation, but this requires that individuals are better than generalists
at the task they specialize in. A new study finds that individual Anelosimus
studiosus spiders do predominantly perform the task they excel at, in line with
their individual personality type, when they are placed in groups.
PMID- 25137588
TI - Dinosaur evolution: feathers up for selection.
AB - A new specimen of the early bird Archaeopteryx shows remarkable plumage
preservation, including pennaceous leg feathers. But whether birds went through a
four-winged stage, and in what exact functional context feathers evolved remains
a matter of debate.
PMID- 25137589
TI - Vision: two plus four equals six.
AB - Using two UV-sensitive visual pigments and the UV-filtering properties of four
mycosporine-like amino acids, mantis shrimp create six spectrally distinct UV
receptors. This is yet another example of the unique ways in which mantis shrimp
have adapted to extract information from their visual world.
PMID- 25137590
TI - Genetics: finding genes for schizophrenia.
AB - New studies have substantially advanced our understanding of the genetic
architecture of schizophrenia, but we are far from identifying the underlying
mutations. We may require new approaches to understand the biological
implications of insights into the genetics of psychiatric disease.
PMID- 25137591
TI - Evolution: ctenophore genomes and the origin of neurons.
AB - Recent sequencing of ctenophore genomes opens a new era in the study of this
unique and phylogenetically distant group. The presence of neurodevelopmental
genes, pre- and postsynaptic modules, and transmitter molecules is consistent
with a single origin of neurons.
PMID- 25137593
TI - Anomalous crystallization as a signature of the fragile-to-strong transition in
metallic glass-forming liquids.
AB - We study the fragile-to-strong (F-S) transition of metallic glass-forming liquids
(MGFLs) by measuring the thermal response during annealing and dynamic heating of
La55Al25Ni5Cu15 glass ribbons fabricated at different cooling rates. We find that
the glasses fabricated in the intermediate regime of cooling rates (15-25 m/s)
exhibit an anomalous crystallization behavior upon reheating as compared to the
glasses formed at other cooling rates. This anomalous crystallization behavior
implies the existence of a thermodynamic F-S transition, could be used as an
alternative method for detecting the F-S transition in MGFLs, and sheds light on
the structure origin of the F-S transition. This work also contributes to
obtaining a general thermodynamic picture of the F-S transition in supercooled
liquids.
PMID- 25137594
TI - Research progress in structure-activity relationship of bioactive peptides.
AB - Bioactive peptides are specific protein fragments that have positive impact on
health. They are important sources of new biomedicine, energy and high
performance materials. The beneficial effects of bioactive peptides are due to
their antioxidant, antihypertensive, anticarcinogenic, antimicrobial, and
immunomodulatory activities. The structure-activity relationship of bioactive
peptides plays a significant role in the development of innovative and
unconventional synthetic polymeric counterparts. It provides the basis of the
stereospecific synthesis, transformation, and development of bioactive peptide
products. This review covers the progress of studies in the structure-activity
relationship of some bioactive peptides including antioxidant peptides,
angiotensin-I-converting enzyme-inhibitory peptides, and anticarcinogenic
peptides in the past decade.
PMID- 25137595
TI - Mn(II/III) complexes as promising redox mediators in quantum-dot-sensitized solar
cells.
AB - The advancement of quantum dot sensitized solar cell (QDSSC) technology depends
on optimizing directional charge transfer between light absorbing quantum dots,
TiO2, and a redox mediator. The nature of the redox mediator plays a pivotal role
in determining the photocurrent and photovoltage from the solar cell.
Kinetically, reduction of oxidized quantum dots by the redox mediator should be
rapid and faster than the back electron transfer between TiO2 and oxidized
quantum dots to maintain photocurrent. Thermodynamically, the reduction potential
of the redox mediator should be sufficiently positive to provide high
photovoltages. To satisfy both criteria and enhance power conversion
efficiencies, we introduced charge transfer spin-crossover Mn(II/III) complexes
as promising redox mediator alternatives in QDSSCs. High photovoltages ~ 1 V were
achieved by a series of Mn poly(pyrazolyl)borates, with reduction potentials ~
0.51 V vs Ag/AgCl. Back electron transfer (recombination) rates were slower than
Co(bpy)3, where bpy = 2,2'-bipyridine, evidenced by electron lifetimes up to 4
orders of magnitude longer. This is indicative of a large barrier to electron
transport imposed by spin-crossover in these complexes. Low solubility prevented
the redox mediators from sustaining high photocurrent due to mass transport
limits. However, with high fill factors (~ 0.6) and photovoltages, they
demonstrate competitive efficiencies with Co(bpy)3 redox mediator at the same
concentration. More positive reduction potentials and slower recombination rates
compared to current redox mediators establish the viability of Mn
poly(pyrazolyl)borates as promising redox mediators. By capitalizing on these
characteristics, efficient Mn(II/III)-based QDSSCs can be achieved with more
soluble Mn-complexes.
PMID- 25137596
TI - Writing an abstract to sell your scholarly work.
PMID- 25137592
TI - Aberrant regulation and function of microRNAs in cancer.
AB - Malignant neoplasms are consistently among the top four leading causes of death
in all age groups in the United States, despite a concerted effort toward
developing novel therapeutic approaches. Our understanding of and therapeutic
strategy for treating each of these neoplastic diseases have been improved
through decades of research on the genetics, signaling pathways, and cellular
biology that govern tumor cell initiation, progression and maintenance. Much of
this work has concentrated on post-translational modifications and abnormalities
at the DNA level, including point mutations, amplifications/deletions, and
chromosomal translocations, and how these aberrant events affect the expression
and function of protein-coding genes. Only recently has a novel class of
conserved gene regulatory molecules been identified as a major contributor to
malignant neoplastic disease. This review focuses on how these small non-coding
RNA molecules, termed microRNAs (miRNAs), can function as oncogenes or tumor
suppressors, and how the misexpression of miRNAs and dysregulation of factors
that regulate miRNAs contribute to the tumorigenic process. Specific focus is
given to more recently discovered regulatory mechanisms that go awry in cancer,
and how these changes alter miRNA expression, processing, and function.
PMID- 25137600
TI - Wolf-Hirschhorn syndrome: a case study and disease overview.
AB - Wolf-Hirschhorn syndrome is caused by a deletion of a segment on the short arm
(p) of chromosome 4. The major features of this disorder include a characteristic
facial appearance known as the "Greek helmet," delayed growth and development;
prenatally and postnatally, intellectual disabilities, and seizures. To provide
comprehensive and appropriate nursing and medical care to infants with Wolf
Hirschhorn syndrome, it is imperative to know and understand the disorder. A case
study of a 36 weeks' gestational age white-Hispanic male infant with Wolf
Hirschhorn syndrome is presented with the purpose of increasing clinical
knowledge and the implications for the clinical nurse and neonatal nurse
practitioner.
PMID- 25137602
TI - What opportunities does NANN provide to support evidence-based practice and
research?
PMID- 25137601
TI - The neonatal nurse's role in preventing abusive head trauma.
AB - Abusive head trauma in infants occurs in 24.6 to 39.8 per 100,000 infants in
developed countries. Abusive head trauma refers to any type of intentional head
trauma an infant sustains, as a result of an injury to the skull or intracranial
contents from a blunt force and/or violent shaking. The clinical question was:
what evidence-based interventions have been implemented by neonatal nurses to
prevent abusive head trauma in infants? PubMed was searched to obtain English
language publications from 2005 to May 2014 for interventions focused on
preventing abusive head trauma using the key term "shaken baby syndrome." A total
of 10 studies were identified that met the inclusion criteria. All of the
interventions targeted prevention of abusive head trauma with information about
abusive head trauma/shaken baby syndrome and the "normal" infant crying
behaviors. Interventions taught parents why infants cried, how to calm the
infants, ways to cope with inconsolable infants, and how to develop a plan for
what to do if they could not cope anymore. Parents who participated in the
interventions were consistently able to explain the information and tell others
about the dangers of shaking infants compared to the control parents. Only 2
studies calculated the preintervention abusive head trauma rate and the
postintervention frequency of abusive head trauma. Each found significant
differences in abusive head trauma.
PMID- 25137603
TI - Hemorrhagic Hairy Polyp Causing Velopharyngeal Dysfunction in a Newborn.
AB - Velopharyngeal dysfunction (VPD) can be secondary to anatomic, neurologic, or
functional maldevelopment in the pediatric population. We present a case of
transient VPD after the removal of a voluminous oropharyngeal hairy polyp in a
newborn with an intact palate. This report sensitizes physicians, speech-language
pathologists, and occupational therapists not only to the repercussions of
oropharyngeal congenital masses, such as hairy polyps, on the feeding mechanisms
of a newborn but also to the possibility of conservative management.
PMID- 25137604
TI - Clinical Factors Affecting Length of Stay After 100 Consecutive Cases of Primary
Cleft Lip Repair.
AB - OBJECTIVE: To analyze the hospital course of 100 consecutive infants after
primary cleft lip repair (PCLR) and identify factors related to length of stay
(LOS). DESIGN: Retrospective analysis of 100 consecutive infants who were
routinely admitted after PCLR. SETTING: Tertiary care center. PATIENTS: One
hundred consecutive infants undergoing PCLR. Demographic and perioperative data
were collected and analyzed. MAIN OUTCOME MEASURE: LOS, planned before data
collection. RESULTS: Male:female ratio was 65:35. Seventy-two infants had
unilateral cleft lip; syndromic association was documented in 15 patients. Mean
age and weight at PCLR were 5.6 +/- 4.0 months and 6.7 +/- 1.3 kg, respectively.
Mean duration of surgery was 2.5 +/- 0.9 hours, and mean duration of general
anesthesia was 3.4 +/- 0.9 hours. A total of 3.3 +/- 1.5 mL of intraoperative
local anesthetic was used per patient. Intravenous fluids were necessary after
transfer from the post-anesthesia care unit to the general ward in 98% of
patients. Almost half (44%) of all patients received intravenous morphine 23
hours or more after hospital admission. Mean LOS was 35.8 +/- 13.9 hours. No
association was identified between patient demographic factors and LOS.
Multivariate linear regression models identified significant positive correlation
between LOS and duration of general anesthesia (P = .002). Greater volume of
postoperative oral intake (P = .000) and higher acetaminophen dosage on the floor
(P = .000) correlated with decreased LOS. CONCLUSIONS: This study identifies
perioperative factors associated with LOS. Our findings question the safety of
routine outpatient or short-stay observation after PCLR.
PMID- 25137605
TI - High risk of adult asthma following severe wheezing in early life.
AB - BACKGROUND: Severe wheezing in early life is associated with an increased risk of
asthma during childhood and adolescence. The aim of the present follow-up was to
investigate the asthma prevalence and risk factors for asthma in adulthood.
METHODS: We have prospectively studied asthma development in 101 children
hospitalized due to severe wheezing before the age of 24 months. The cohort was
re-investigated at a mean age of 27 years and tested for bronchial hyper
responsiveness and allergic sensitization. The response rate in adulthood was 81%
(82/101). The results were compared with a population-based, age-matched control
group (n = 1,210) recruited from the West Sweden Asthma Study. RESULTS: Current
doctor-diagnosed asthma was found in 37% (30/82) compared with 7% (82/1,210) in
the control group. The risk of adult asthma in the cohort compared with the
control group was increased 10-fold (adjusted OR 10.0, 95% CI 5.3-18.7),
independently of allergic rhinitis, gender, smoking and heredity. Within the
cohort, current allergy (aOR 9.6, 95% CI 3.0-31.2) and female gender (aOR 3.2,
95% CI 1.1-9.3) independently increased the risk of adult asthma. Females with
current allergy had the highest risk of adult asthma (OR 29.4, 95% CI 5.0-173.3),
compared with males without allergy. When separately adjusting for factors
present at admission in early life within the cohort, a family history of asthma
was a significant risk factor for asthma in adulthood (aOR 4.0, 95% CI 1.3-12.5).
CONCLUSION: Subjects with severe early wheezing have a 10-fold increase in the
risk of adult asthma compared to an age-matched control group, adjusted for
allergic rhinitis, gender, smoking and heredity.
PMID- 25137606
TI - Determination of glyphosate and aminomethylphosphonic acid in aqueous soil
matrices: a critical analysis of the 9-fluorenylmethyl chloroformate
derivatization reaction and application to adsorption studies.
AB - The assessment of the environmental fate of glyphosate and its degradation
product (aminomethylphosphonic acid) is of great interest given the widespread
use of the herbicide. Studies of adsorption-desorption and transport processes in
soils require analytical methods with sensitivity, accuracy, and precision
suitable for determining the analytes in aqueous equilibrium solutions of varied
complexity. In this work, the effect of factors on the yield of the
derivatization of both compounds with 9-fluorenylmethyl chloroformate for
applying in aqueous solutions derived from soils was evaluated through factorial
experimental designs. Interference effects coming from background electrolytes
and soil matrices were established. The whole method had a linear response up to
640 ng/mL (R(2) > 0.999) under optimized conditions for high-performance liquid
chromatography with fluorescence detection. Limits of detection were 0.6 and 0.4
ng/mL for glyphosate and aminomethylphosphonic acid, respectively. The relative
standard deviation was 4.4% for glyphosate (20 ng/mL) and 5.9% for
aminomethylphosphonic acid (10 ng/mL). Adsorption of compounds on four different
soils was assessed. Isotherm data fitted well the Freundlich model (R(2) > 0.97).
Kf constants varied between 93 +/- 3.1 and 2045 +/- 157 for glyphosate and
between 99 +/- 4.1 and 1517 +/- 56 (MUg(1-1/) (n) mL(1/) (n) ( ) g(-1) ) for
aminomethylphosphonic acid, showing the broad range of applicability of the
proposed method.
PMID- 25137612
TI - Collagen and related extracellular matrix proteins in atherosclerotic plaque
development.
AB - PURPOSE OF REVIEW: The structure, composition and turnover of the extracellular
matrix (ECM) as well as cell-matrix interactions are crucial in the developing
atherosclerotic plaque. There is a need for further insight into specific
proteins in the ECM and their functions in the developing plaque, and during the
last few years a number of publications have highlighted this very important
field of research. These novel findings will be addressed in the present review.
RECENT FINDINGS: This review covers literature focused on collagen and ECM
proteins interacting with collagen, and what their roles may be in plaque
development. SUMMARY: Acute myocardial infarction and stroke are common diseases
that cause disability and mortality, and the underlying mechanism is often the
rupture of a vulnerable atherosclerotic plaque. The vascular ECM and the tissue
repair in the atherosclerotic lesion are important players in plaque progression.
Understanding how specific proteins in the ECM interact with cells in the plaque
and affect the fate of the plaque can lead to new treatments for cardiovascular
disease.
PMID- 25137613
TI - Electrochemical determination of the density of states of nanostructured NiO
films.
AB - Mesoporous p-type NiO films were prepared by aerosol-assisted chemical vapor
deposition (AACVD) and characterized by X-ray diffraction (XRD). The
nanostructure of the films was investigated by field emission gun scanning
electron microscopy (FEG-SEM). The density of states (DOS) in these
nanostructured films has been determined by means of electrochemical impedance
spectroscopy and cyclic voltammetry. The analysis reveals an exponential
distribution of band gap states above the valence band that extends around 1.5
eV. In addition, monoenergetic states were also identified which overlap with the
exponential distribution. This distribution of states has an enormous influence
in the electronic processes of the devices in which NiO electrodes are employed
(electrochromism, water splitting or energy storage). Especially, in p-type dye
sensitized solar cells (p-DSCs), it is thought that intra-band-gap states are
responsible for the fast observed recombination processes, whose existence and
distribution has not been clearly determined yet and are now confirmed and
quantified by our analysis. This provides a better comprehension of the
recombination events which represent one of the main losses in p-DSCs.
PMID- 25137614
TI - Does hindered transport theory apply to desalination membranes?
AB - As reverse osmosis (RO) and nanofiltration polyamide membranes become
increasingly used for water purification, prediction of pollutant transport is
required for membrane development and process engineering. Many popular models
use hindered transport theory (HTT), which considers a spherical solute moving
through an array of fluid-filled rigid cylindrical pores. Experiments and
molecular dynamic simulations, however, reveal that polyamide membranes have a
distinctly different structure of a "molecular sponge", a network of randomly
connected voids widely distributed in size. In view of this disagreement, this
study critically examined the validity of HTT by directly measuring diffusivities
of several alcohols within a polyamide film of commercial RO membrane using
attenuated total reflection-FTIR. It is found that measured diffusivities deviate
from HTT predictions by as much as 2-3 orders of magnitude. This result indicates
that HTT does not adequately describe solute transport in desalination membranes.
As a more adequate alternative, the concept of random resistor networks is
suggested, with resistances described by models of activated transport in "soft"
polymers without a sharp size cutoff and with a proper address of solute
partitioning.
PMID- 25137615
TI - Generalized workflow for generating highly predictive in silico off-target
activity models.
AB - Chemical structure data and corresponding measured bioactivities of compounds are
nowadays easily available from public and commercial databases. However, these
databases contain heterogeneous data from different laboratories determined under
different protocols and, in addition, sometimes even erroneous entries. In this
study, we evaluated the use of data from bioactivity databases for the generation
of high quality in silico models for off-target mediated toxicity as a decision
support in early drug discovery and crop-protection research. We chose human
acetylcholinesterase (hAChE) inhibition as an exemplary end point for our case
study. A standardized and thorough quality management routine for input data
consisting of more than 2,200 chemical entities from bioactivity databases was
established. This procedure finally enables the development of predictive QSAR
models based on heterogeneous in vitro data from multiple laboratories. An
extended applicability domain approach was used, and regression results were
refined by an error estimation routine. Subsequent classification augmented by
special consideration of borderline candidates leads to high accuracies in
external validation achieving correct predictive classification of 96%. The
standardized process described herein is implemented as a (semi)automated
workflow and thus easily transferable to other off-targets and assay readouts.
PMID- 25137616
TI - Prevalence and Characteristics of Chemical Intolerance: A Japanese Population
Based Study.
AB - Population-based cross-sectional study was performed to estimate the prevalence
of chemical intolerance and to examine the characteristics of the sample. A Web
based survey was conducted that included 7,245 adults in Japan. The criteria for
chemical intolerance proposed by Skovbjerg yielded a prevalence of 7.5% that was
approximately consistent with that reported from a Danish population-based
survey. Female gender, older age, and renovation in the house during the past 7
years were positively associated with chemical intolerance. Improvements in the
condition were observed with daily ventilation habits. Medical history of atopic
dermatitis, allergic rhinitis, food allergy, multiple chemical sensitivity, and
depression were associated with chemical intolerance. Fatigue, depressed mood,
and somatic symptoms were also positively correlated with chemical intolerance.
Better elucidation of the causes, comorbidities, concomitants, and consequences
of chemical intolerance has the potential to provide effective solutions for its
prevention and treatment.
PMID- 25137617
TI - Workplace psychosocial factors associated with hypertension in the U.S.
workforce: a cross-sectional study based on the 2010 national health interview
survey.
AB - OBJECTIVE: To explore associations between self-reported hypertension and
workplace psychosocial factors that are common among U.S. workers and to identify
industries and occupations (I&Os) that are associated with a high prevalence of
hypertension, even after adjustment for common known risk factors. METHODS: Data
from the 2010 National Health Interview Survey were used to examine relationships
between the prevalence of self-reported hypertension and job insecurity, hostile
work environment, work- family imbalance, work hours and I&O. RESULTS: Job
insecurity (adjusted prevalence ratio (aPR): 1.11; 95% confidence interval (CI):
1.04-1.19)) and hostile work environment (aPR: 1.15; 95% CI: 1.03-1.29) were
significantly associated with hypertension. Hypertension prevalence was
significantly elevated among those employed in Healthcare Support occupations and
Public Administration industries. CONCLUSION: Addressing hostile work
environments and the stress associated with job insecurity may improve workers'
health. Other occupational factors that contribute to the variation in prevalence
of hypertension by I&O should be sought.
PMID- 25137618
TI - Comparison of duplex stabilizing properties of 2'-fluorinated nucleic acid
analogues with furanose and non-furanose sugar rings.
AB - We compare the duplex stabilizing properties of 2'-fluorinated nucleic acid
analogues with furanose and non-furanose ring systems and dissect the relative
contributions of hydration, sugar conformation, and fluorine configuration toward
the overall T(m) value. We find that the stabilization imparted by fluorine
substitution is additive over that obtained by restricting the conformation of
the sugar ring itself. Our studies support further evaluation of fluorinated
nucleic acid analogues with non-furanose sugar rings as surrogates of 2'-F RNA
for therapeutic antisense applications.
PMID- 25137620
TI - Organophosphorus pesticide chlorpyrifos and its metabolites alter the expression
of biomarker genes of differentiation in D3 mouse embryonic stem cells in a
comparable way to other model neurodevelopmental toxicants.
AB - There are discrepancies about whether chlorpyrifos is able to induce
neurodevelopmental toxicity or not. We previously reported alterations in the
pattern of expression of biomarker genes of differentiation in D3 mouse embryonic
stem cells caused by chlorpyrifos and its metabolites chlorpyrifos-oxon and 3,5,6
trichloro-2-pyridinol. Now, we reanalyze these data comparing the effects on
these genes with those caused in the same genes by retinoic acid, valproic acid,
and penicillin-G (model compounds considered as strong, weak, and non
neurodevelopmental toxicants, respectively). We also compare the effects of
chlorpyrifos and its metabolites on the cell viability of D3 cells and 3T3 mouse
fibroblasts with the effects caused in the same cells by the three model
compounds. We conclude that chlorpyrifos and its metabolites act, regarding these
end-points, as the weak neurodevelopmental toxicant valproic acid, and
consequently, a principle of caution should be applied avoiding occupational
exposures in pregnant women. A second independent experiment run with different
cellular batches coming from the same clone obtained the same result as the first
one.
PMID- 25137619
TI - Propylene cross-bridged macrocyclic bifunctional chelator: a new design for
facile bioconjugation and robust (64)Cu complex stability.
AB - The first macrocyclic bifunctional chelator incorporating propylene cross-bridge
was efficiently synthesized from cyclam in seven steps. After the introduction of
an extra functional group for facile conjugation onto the propylene cross-bridge,
the two carboxylic acid pendants could contribute to strong coordination of
Cu(II) ions, leading to a robust Cu complex. The cyclic RGD peptide conjugate of
PCB-TE2A-NCS was prepared and successfully radiolabeled with (64)Cu ion. The
radiolabeled peptide conjugate was evaluated in vivo through a biodistribution
study and animal PET imaging to demonstrate high tumor uptake with low
background.
PMID- 25137621
TI - The clinical utility of vocal dosimetry for assessing voice rest.
AB - OBJECTIVES/HYPOTHESIS: Voice rest is frequently recommended following surgical
disruption of vocal fold epithelium, but patients report variable adherence to
voice rest recommendations. The objective of this study was to assess the
clinical utility of an ambulatory vocal dosimeter for measuring adherence to
voice rest recommendations. STUDY DESIGN: Outcomes research. METHODS: Part 1: To
determine the utility of the dosimeter in nonclinical use, the relationship
between self-reported voice use and dosimeter measurements was examined in normal
subjects (n = 11) who prospectively logged voice use while wearing the dosimeter.
Part 2: To determine clinical utility of the dosimeter, patients undergoing vocal
fold surgery for which postoperative voice rest was recommended (n = 11) wore a
dosimeter for 2 days prior to and 2 days after surgery. Phonation percent and
sound level were compared at baseline and during voice rest. RESULTS: The
dosimeter performed as hypothesized with both normal subjects and patients. A
moderate correlation (r = 0.62) was noted between self-reported voice use and
dosimeter measurements in normal subjects. In patients on voice rest, a
statistically and clinically significant decrease was observed in measured voice
use, both in phonation time (P = .002) and intensity of phonation (P = .004).
CONCLUSIONS: Ambulatory vocal dosimetry may have clinical utility for assessing
adherence to voice rest recommendations. This information will be useful for the
design of future studies on voice rest.
PMID- 25137623
TI - Plasmon enhanced terahertz emission from single layer graphene.
AB - We show that surface plasmons, excited with femtosecond laser pulses on
continuous or discontinuous gold substrates, strongly enhance the generation and
emission of ultrashort, broadband terahertz pulses from single layer graphene.
Without surface plasmon excitation, for graphene on glass, 'nonresonant laser
pulse-induced photon drag currents' appear to be responsible for the relatively
weak emission of both s- and p-polarized terahertz pulses. For graphene on a
discontinuous layer of gold, only the emission of the p-polarized terahertz
electric field is enhanced, whereas the s-polarized component remains largely
unaffected, suggesting the presence of an additional terahertz generation
mechanism. We argue that in the latter case, 'surface-plasmon-enhanced optical
rectification', made possible by the lack of inversion symmetry at the graphene
on gold surface, is responsible for the strongly enhanced emission. The
enhancement occurs because the electric field of surface plasmons is localized
and enhanced where the graphene is located: at the surface of the metal. We
believe that our results point the way to small, thin, and more efficient
terahertz photonic devices.
PMID- 25137622
TI - Morquio A syndrome-associated mutations: a review of alterations in the GALNS
gene and a new locus-specific database.
AB - Morquio A syndrome (mucopolysaccharidosis IVA) is an autosomal recessive disorder
that results from deficient activity of the enzyme N-acetylgalactosamine-6
sulfatase (GALNS) due to alterations in the GALNS gene, which causes major
skeletal and connective tissue abnormalities and effects on multiple organ
systems. The GALNS alterations associated with Morquio A are numerous and
heterogeneous, and new alterations are continuously identified. To aid detection
and interpretation of GALNS alterations, from previously published research, we
provide a comprehensive and up-to-date listing of 277 unique GALNS alterations
associated with Morquio A identified from 1,091 published GALNS alleles. In
agreement with previous findings, most reported GALNS alterations are missense
changes and even the most frequent alterations are relatively uncommon. We found
that 48% of patients are assessed as homozygous for a GALNS alteration, 39% are
assessed as heterozygous for two identified GALNS alterations, and in 13% of
patients only one GALNS alteration is detected. We report here the creation of a
locus-specific database for the GALNS gene (http://galns.mutdb.org/) that
catalogs all reported alterations in GALNS to date. We highlight the challenges
both in alteration detection and genotype-phenotype interpretation caused in part
by the heterogeneity of GALNS alterations and provide recommendations for
molecular testing of GALNS.
PMID- 25137625
TI - Response to "are the results likely biased toward the null?".
PMID- 25137626
TI - N-doped graphene: an alternative carbon-based matrix for highly efficient
detection of small molecules by negative ion MALDI-TOF MS.
AB - Gas-phase N-doped graphene (gNG) was synthesized by a modified thermal annealing
method using gaseous melamine as nitrogen source and then for the first time
applied as a matrix in negative ion matrix-assisted laser desorption/ionization
time-of-flight mass spectrometry (MALDI-TOF MS) for small molecule analysis.
Unlike the complicated adducts produced in positive ion mode, MS spectra obtained
on gNG matrix in negative ion mode was only featured by deprotonated molecule ion
peaks without matrix interference. By the gNG assisted desorption/ionization
(D/I) process, some applications were carried out on a wide range of low
molecular weight (MW) analytes including amino acids, fatty acids, peptides,
anabolic androgenic steroids as well as anticancer drugs, with an extraordinary
laser desorption/ionization (LDI) efficiency over traditional alpha-cyano-4
hydroxycinnamic acid (CHCA) and other carbon-based materials in the negative ion
detection mode. By comparison of a series of graphene-based matrixes, two main
factors of matrix gNG were unveiled to play a decisive role in assisting negative
ion D/I process: a well-ordered pi-conjugated system for laser absorption and
energy transfer; pyridinic-doped nitrogen species functioning as deprotonation
sites for proton capture on negative ionization. The good salt tolerance and high
sensitivity allowed further therapeutic monitoring of anticancer drug nilotinib
in the spiked human serum, a real case of biology. Signal response was definitely
obtained between 1 mM and 1 MUM, meeting the demand of assessing drug level in
the patient serum. This work creates a new application branch for nitrogen-doped
graphene and provides an alternative solution for small molecule analysis.
PMID- 25137627
TI - Effective ion mobility calculations for macromolecules by scattering on electron
clouds.
AB - Broad commercialization and increasing resolving power of ion mobility
spectrometry/mass spectrometry (IMS/MS) platforms have engendered an explosion of
IMS applications to structural characterization of gas-phase biomolecules. That
has renewed interest in more accurate and rapid ion mobility calculations that
are needed to elicit ion geometries from the measurements. An approach based on
scattering on electron density isosurfaces (SEDI) that mirrors the physics of
molecular collisions was proven superior to the common methods involving atomic
coordinates a decade ago but has remained impractical for large ions because of
extreme computational demands. Here, we accelerate SEDI by up to ~500 times using
the fragment molecular orbital approach for surface generation and the
multiplexed scattering algorithm in conjunction with the new grid extrapolation
procedure for cross section evaluations. Parallelization of the code on a
supercomputer has produced major further speed gains, allowing SEDI calculations
for proteins (defined by over a million surface points) with a precision of <0.1%
in 1 min. Initial tests reveal the anticipated dependence of mobility on the ion
charge state and lower cross sections in view of reduced surface roughness.
Present developments are expected to lead to broad application of SEDI in IMS
studies of macromolecules, enabling more accurate and reliable structural
assignments.
PMID- 25137624
TI - A proposal for assessing study quality: Biomonitoring, Environmental
Epidemiology, and Short-lived Chemicals (BEES-C) instrument.
AB - The quality of exposure assessment is a major determinant of the overall quality
of any environmental epidemiology study. The use of biomonitoring as a tool for
assessing exposure to ubiquitous chemicals with short physiologic half-lives
began relatively recently. These chemicals present several challenges, including
their presence in analytical laboratories and sampling equipment, difficulty in
establishing temporal order in cross-sectional studies, short- and long-term
variability in exposures and biomarker concentrations, and a paucity of
information on the number of measurements required for proper exposure
classification. To date, the scientific community has not developed a set of
systematic guidelines for designing, implementing and interpreting studies of
short-lived chemicals that use biomonitoring as the exposure metric or for
evaluating the quality of this type of research for WOE assessments or for peer
review of grants or publications. We describe key issues that affect epidemiology
studies using biomonitoring data on short-lived chemicals and propose a
systematic instrument--the Biomonitoring, Environmental Epidemiology, and Short
lived Chemicals (BEES-C) instrument--for evaluating the quality of research
proposals and studies that incorporate biomonitoring data on short-lived
chemicals. Quality criteria for three areas considered fundamental to the
evaluation of epidemiology studies that include biological measurements of short
lived chemicals are described: 1) biomarker selection and measurement, 2) study
design and execution, and 3) general epidemiological study design considerations.
We recognize that the development of an evaluative tool such as BEES-C is neither
simple nor non-controversial. We hope and anticipate that the instrument will
initiate further discussion/debate on this topic.
PMID- 25137630
TI - Trichomonas vaginalis infections are rare among young patients attending an STI
clinic in Sweden.
PMID- 25137631
TI - Low-density lipoprotein-mimicking nanoparticles for tumor-targeted theranostic
applications.
AB - This study introduces multifunctional lipid nanoparticles (LNPs), mimicking the
structure and compositions of low-density lipoproteins, for the tumor-targeted co
delivery of anti-cancer drugs and superparamagnetic nanocrystals. Paclitaxel (4.7
wt%) and iron oxide nanocrystals (6.8 wt%, 11 nm in diameter) are co-encapsulated
within folate-functionalized LNPs, which contain a cluster of nanocrystals with
an overall diameter of about 170 nm and a zeta potential of about -40 mV. The
folate-functionalized LNPs enable the targeted detection of MCF-7, human breast
adenocarcinoma expressing folate receptors, in T2 -weighted magnetic resonance
images as well as the efficient intracellular delivery of paclitaxel. Paclitaxel
free LNPs show no significant cytotoxicity up to 0.2 mg mL(-1) , indicating the
excellent biocompatibility of the LNPs for intracellular drug delivery
applications. The targeted anti-tumor activities of the LNPs in a mouse tumor
model suggest that the low-density lipoprotein-mimetic LNPs can be an effective
theranostic platform with excellent biocompatibility for the tumor-targeted co
delivery of various anti-cancer agents.
PMID- 25137632
TI - Influence of emulsifier concentration on nanoemulsion gelation.
AB - Nanoemulsion gels are a new class of soft materials that manifest stronger
elasticity even at lower dispersed phase volume fraction. In this work, gelation
in 40 wt % canola oil-in-water nanoemulsions was investigated as a function of
emulsifier type (anionic sodium dodecyl sulfate (SDS) or nonionic Tween 20) and
concentration. It was observed that the liquid nanoemulsions transformed into
viscoelastic gels at a specific concentration range of SDS, whereas no gelation
was observed for Tween 20. The apparent viscosity, yield stress, and storage
modulus of the nanogels increased with SDS concentration until 15 times critical
micelle concentration (CMC), thereafter decreased steadily as the gelation
weakened beginning 20 CMC. Three regimes of colloidal interactions in the
presence of emulsifier were proposed. (1) Repulsive gelation: at low SDS
concentration (0.5-2 times CMC) the repulsive charge cloud around the
nanodroplets acted as interfacial shell layer that significantly increased the
effective volume fraction of the dispersed phase (phi(eff)). When phi(eff) became
comparable to the volume fraction required for maximal random jamming,
nanoemulsions formed elastic gels. (2) Attractive gelation: as the SDS
concentration increased to 5-15 times CMC, phi(eff) dropped due to charge
screening by more counterions from SDS, but depletion attractions generated by
micelles in the continuous phase led to extensive droplet aggregation which
immobilized the continuous phase leading to stronger gel formation. (3) Decline
in gelation due to oscillatory structural forces (OSF): at very high SDS
concentration (20-30 time CMC), structural forces were manifested due to the
layered-structuring of excess micelles in the interdroplet regions resulting in
loss of droplet aggregation. Tween 20 nanoemulsions, on the other hand, did not
show repulsive gelation due to lack of charge cloud, while weak depletion
attraction and early commencement of OSF regime leading to liquid-like behavior
at all concentrations. The nanogels possess great potential for use in low-fat
foods, pharmaceuticals and cosmetic products.
PMID- 25137633
TI - Riboswitch engineering - making the all-important second and third steps.
AB - Synthetic biology uses our understanding of biological systems to develop
innovative solutions for challenges in fields as diverse as genetic control and
logic devices, bioremediation, materials production or diagnostics and therapy in
medicine by designing new biological components. RNA-based elements are key
components of these engineered systems. Their structural and functional diversity
is ideal for generating regulatory riboswitches that react with many different
types of output to molecular and environmental signals. Recent advances have
added new sensor and output domains to the existing toolbox, and demonstrated the
portability of riboswitches to many different organisms. Improvements in
riboswitch design and screens for selecting in vivo active switches provide the
means to isolate riboswitches with regulatory properties more like their natural
counterparts.
PMID- 25137634
TI - Functional characterization of SjB10, an intracellular serpin from Schistosoma
japonicum.
AB - SUMMARY Serine protease inhibitors (serpin) play essential roles in many
organisms. Mammalian serpins regulate the blood coagulation, fibrinolysis,
inflammation and complement activation pathways. In parasitic helminths, serpins
are less well characterized, but may also be involved in evasion of the host
immune response. In this study, a Schistosoma japonicum serpin (SjB10),
containing a 1212 bp open reading frame (ORF), was cloned, expressed and
functionally characterized. Sequence analysis, comparative modelling and
structural-based alignment revealed that SjB10 contains the essential structural
motifs and consensus secondary structures of inhibitory serpins. Transcriptional
profiling demonstrated that SjB10 is expressed in adult males, schistosomula and
eggs but particularly in the cercariae, suggesting a possible role in cercarial
penetration of mammalian host skin. Recombinant SjB10 (rSjB10) inhibited
pancreatic elastase (PE) in a dose-dependent manner. rSjB10 was recognized
strongly by experimentally infected rat sera indicating that native SjB10 is
released into host tissue and induces an immune response. By immunochemistry,
SjB10 localized in the S. japonicum adult foregut and extra-embryonic layer of
the egg. This study provides a comprehensive demonstration of sequence and
structural-based analysis of a functional S. japonicum serpin. Furthermore, our
findings suggest that SjB10 may be associated with important functional roles in
S. japonicum particularly in host-parasite interactions.
PMID- 25137629
TI - Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801
induced behavioral impairments and enhances associative learning in rodents.
AB - Positive allosteric modulators (PAMs) of the M4 muscarinic acetylcholine receptor
(mAChR) represent a novel approach for the treatment of psychotic symptoms
associated with schizophrenia and other neuropsychiatric disorders. We recently
reported that the selective M4 PAM VU0152100 produced an antipsychotic drug-like
profile in rodents after amphetamine challenge. Previous studies suggest that
enhanced cholinergic activity may also improve cognitive function and reverse
deficits observed with reduced signaling through the N-methyl-d-aspartate subtype
of the glutamate receptor (NMDAR) in the central nervous system. Prior to this
study, the M1 mAChR subtype was viewed as the primary candidate for these actions
relative to the other mAChR subtypes. Here we describe the discovery of a novel
M4 PAM, VU0467154, with enhanced in vitro potency and improved pharmacokinetic
properties relative to other M4 PAMs, enabling a more extensive characterization
of M4 actions in rodent models. We used VU0467154 to test the hypothesis that
selective potentiation of M4 receptor signaling could ameliorate the behavioral,
cognitive, and neurochemical impairments induced by the noncompetitive NMDAR
antagonist MK-801. VU0467154 produced a robust dose-dependent reversal of MK-801
induced hyperlocomotion and deficits in preclinical models of associative
learning and memory functions, including the touchscreen pairwise visual
discrimination task in wild-type mice, but failed to reverse these stimulant
induced deficits in M4 KO mice. VU0467154 also enhanced the acquisition of both
contextual and cue-mediated fear conditioning when administered alone in wild
type mice. These novel findings suggest that M4 PAMs may provide a strategy for
addressing the more complex affective and cognitive disruptions associated with
schizophrenia and other neuropsychiatric disorders.
PMID- 25137636
TI - Dependency denied: health inequalities in the neo-liberal era.
AB - The ways in which inequality generates particular population health outcomes
remains a major source of dispute within social epidemiology and medical
sociology. Wilkinson and Pickett's The Spirit Level (2009), undoubtedly
galvanised thinking across the disciplines, with its emphasis on how income
inequality shapes the distribution of health and social problems. In this paper,
we argue that their focus on income inequality, whilst important, understates the
role of neoliberal discourses and practises in making sense of contemporary
inequality and its health-related consequences. Many quantitative studies have
demonstrated that more neoliberal countries have poorer health compared to less
neoliberal countries, but there are few qualitative studies which explore how
neoliberal discourses shape accounts and experiences and what protections and
resources might be available to people. This article uses findings from a
qualitative psycho-social study employing biographical-narrative interviews with
women in Salford (England) to understand experiences of inequality as posited in
The Spirit Level. We found evidence for the sorts of damages resulting from
inequality as proposed in The Spirit Level. However, in addition to these, the
most striking finding was the repeated articulation of a discourse which we have
termed "no legitimate dependency". This was something both painful and damaging,
where dependency of almost any sort was disavowed and responsibility was assumed
by the self or "othered" in various ways. No legitimate dependency, we propose,
is a partial (and problematic) internalisation of neoliberal discourses which
becomes naturalised and unquestioned at the individual level. We speculate that
these sorts of discourses in conjunction with a destruction of protective
resources (both material and discursive), lead to an increase in strain and
account in part for well-known damages consequent on life in an unequal society.
We conclude that integrating understandings of neoliberalism into theorising
about inequality enriches sociological perspectives in this area.
PMID- 25137635
TI - The association between psychosocial stress and mortality is mediated by
lifestyle and chronic diseases: the Hoorn Study.
AB - Psychosocial stress is associated with chronic disease. We evaluated whether in
the general population the number of stressful life events is associated with
risk of mortality and whether this association is mediated by behavioral factors
and morbidities. We conducted this study in the Hoorn cohort; a population-based
cohort study among older men and women. Our main variable of interest was the
number of stressful life events experienced during the previous 5 years, which
were assessed by questionnaire. We calculated Cox proportional hazard ratios
(HRs) for all-cause and cause-specific mortality during follow-up for those who
experienced stressful life events compared to those who did not. We included 2385
participants (46% male; 62 +/- 7 years). During 20 years of follow-up 834 (35%)
participants died, of whom 239 (28.6%) died of cardiovascular disease. Compared
to the group with no stressful life events, the age, sex and socioeconomic status
adjusted HRs (with 95% confidence intervals) for all-cause mortality, for the
groups who had 1 event, 2 events, 3 events and >=4 events were 0.89 (0.72-1.09),
1.01 (0.81-1.24), 1.29 (1.00-1.66) and 1.44 (1.08-1.92), respectively. Similar
results were observed for cardiovascular mortality. Mediation analysis showed
that smoking, prevalent type 2 diabetes and cardiovascular disease were
statistically significant mediators of the association between the number of
stressful life events and mortality. Having 3 or more stressful life events is
associated with a significantly increased risk for mortality in an elderly
population-based cohort. This association is mediated by smoking, type 2 diabetes
and cardiovascular disease.
PMID- 25137637
TI - Histamine H1 receptor cell membrane chromatography online high-performance liquid
chromatography with mass spectrometry method reveals houttuyfonate as an
activator of the histamine H1 receptor.
AB - Allergy is an abnormal reaction of the body to an allergen. Histamine is
responsible for many of the acute symptoms of allergic diseases. Many of the
allergic and inflammatory actions of histamine are mediated by the histamine H1
receptor. In the present study, we established a two-dimensional histamine H1
receptor/cell membrane chromatography with online high-performance liquid
chromatography and mass spectrometry method for screening potential histamine
activating components in a traditional Chinese medicine injection. The
specification of the method was validated by screening, separating, and
identifying a mixed standard solution of diphenhydramine hydrochloride,
gefitinib, tamsulosin, and nitrendipine. The Yujin injection, an example of
traditional Chinese medicine injection, was screened and potential allergic
components acting on the histamine H1 receptor were identified. A Ca(2+) flux
assay showed that houttuyfonate and Yujin injection induced calcium release in a
dose-dependent manner. This suggests that houttuyfonate is an activator of the
histamine H1 receptor. The mechanism of houttuyfonate activation involves
phosphorylation of the inositol-1,4,5-trisphosphate receptor. In conclusion, this
two-dimensional method can rapidly detect and enrich target components isolated
from the Yujin injection. This indicates that individuals with an overexpression
of the histamine H1 receptor should be aware of possible allergic reactions when
receiving the Yujin injection.
PMID- 25137639
TI - Role of Pb(II) defects in the mechanism of dissolution of plattnerite (beta-PbO2)
in water under depleting chlorine conditions.
AB - Destabilization of lead corrosion scales present in plumbing materials used in
water distribution systems results in elevated lead concentrations in drinking
water. Soluble lead release caused by changes in water chemistry has been linked
to dissolution of lead carbonate and/or lead oxide solid phases. Although prior
studies have examined the effects of varying water chemistry on the dissolution
of plattnerite (beta-PbO2), beta-PbO2 dissolution under depleting chlorine
conditions is poorly understood. This paper reports results obtained for long
term batch dissolution experiments for solid phase beta-PbO2 under depleting
chlorine conditions. Results indicate that the initial availability of free
chlorine effectively depresses dissolved lead concentrations released from beta
PbO2. However, the dissolved lead levels remained low (~4 MUg/L) even after free
chlorine was depleted. Detailed spectroscopic characterization of solid samples
collected during the beta-PbO2 experiments indicates that changes in the
electronic structure of PbO2 occurred during the dissolution. This further points
out that Pb2+ defects present in crystalline beta-PbO2 play a dominant role in
the dissolution of this solid phase.
PMID- 25137638
TI - Dual effects of familial Alzheimer's disease mutations (D7H, D7N, and H6R) on
amyloid beta peptide: correlation dynamics and zinc binding.
AB - Although the N-terminal region of Amyloid beta (Abeta) peptides plays dual roles
as metal-coordinating sites and conformational modulator, few studies have been
performed to explore the effects of mutations at this region on the overall
conformational ensemble of Abeta and the binding propensity of metal ions. In
this work, we focus on how three familial Alzheimer's disease mutations (D7H,
D7N, and H6R) alter the structural characteristics and thermodynamic stabilities
of Abeta42 using molecular dynamics simulations. We observe that each mutation
displays increased beta-sheet structures in both N and C termini. In particular,
both the N terminus and central hydrophobic region of D7H can form stable beta
hairpin structures with its C terminus. The conserved turn structure at Val24
Lys28 in all peptides and Zn2+-bound Abeta42 is confirmed as the common
structural motif to nucleate folding of Abeta. Each mutant can significantly
increase the solvation free energy and thus enhance the aggregation of Abeta
monomers. The correlation dynamics between Abeta(1-16) and Abeta(17-42) fragments
are elucidated by linking the domain motions with the corresponding structured
conformations. We characterize the different populations of correlated domain
motions for each mutant from a more macroscopic perspective, and unexpectedly
find that Zn2+-bound Abeta42 ensemble shares the same populations as Abeta42,
indicating that the binding of Zn2+ to Abeta follows the conformational selection
mechanism, and thus is independent of domain motions, even though the structures
of Abeta have been modified at a residue level.
PMID- 25137640
TI - Impaired development of neural-crest cell-derived organs and intellectual
disability caused by MED13L haploinsufficiency.
AB - MED13L is a component subunit of the Mediator complex, an important regulator of
transcription that is highly conserved across eukaryotes. Here, we report MED13L
disruption in a translocation t(12;19) breakpoint of a patient with Pierre-Robin
syndrome, moderate intellectual disability, craniofacial anomalies, and muscular
defects. The phenotype is similar to previously described patients with MED13L
haploinsufficiency. Knockdown of MED13L orthologue in zebrafish, med13b, showed
early defective migration of cranial neural crest cells (NCCs) that contributed
to cartilage structure deformities in the later stage, recapitulating
craniofacial anomalies seen in human patients. Notably, we observed abnormal
distribution of developing neurons in different brain regions of med13b morphant
embryos, which could be rescued upon introduction of full-length human MED13L
mRNA. To compare with mammalian system, we suppressed MED13L expression by short
hairpin RNA in ES-derived human neural progenitors, and differentiated them into
neurons. Transcriptome analysis revealed differential expression of components of
Wnt and FGF signaling pathways in MED13L-deficient neurons. Our finding provides
a novel insight into the mechanism of overlapping phenotypic outcome targeting
NCCs derivatives organs in patients with MED13L haploinsufficiency, and
emphasizes a clinically recognizable syndromic phenotype in these patients.
PMID- 25137641
TI - Hippocampal network oscillations - recent insights from in vitro experiments.
AB - Network oscillations are present throughout the mammalian brain. They are
important for certain cognitive functions, such as learning and memory. The
hippocampus exhibits prominent oscillations similar to those seen in other parts
of the cortex. Due to its highly organised lamellar structure, ex vivo and in
vitro preparations from the hippocampus have provided experimental models within
which to study network oscillations. As such, experiments in hippocampal slices
continue to progress our understanding about both the mechanisms and functions of
cortical network oscillations. Here, advances from the past two years are
summarised, and the current state of the field discussed.
PMID- 25137642
TI - Novel electrochemical fingerprinting methods for the precise determination of
Pt(shell) coverage on Ru(core) nanoparticles.
AB - The surface composition of nanoparticles is critical in defining their chemical
and electrochemical properties. However, there are a limited number of tools that
can rapidly and reliably establish these important characteristics at this small
scale. In the present work, a series of Rucore@Ptshell nanoparticles (2 or 3 nm
diameter Ru core, 0 to 2 monolayers of Pt in the shell layer) were synthesized
and several novel electrochemical fingerprinting methods were developed to
determine the Pt shell characteristics. These involved tracking the charge
associated with the reduction of the oxide film formed on the exposed Rucore, as
well as the potential and charge associated with COads stripping, giving the
precise coverage of the first and second Pt monolayer, respectively.
PMID- 25137643
TI - Trypanocidal activity of free and nanoencapsulated curcumin on Trypanosoma
evansi.
AB - This study aimed to evaluate in vitro and in vivo trypanocidal activity of free
and nanoencapsulated curcumin against Trypanosoma evansi. In vitro efficacy of
free curcumin (CURC) and curcumin-loaded in lipid-core nanocapsules (C-LNCs) was
evaluated to verify their lethal effect on T. evansi. To perform the in vivo
tests, T. evansi-infected animals were treated with CURC (10 and 100 mg kg(-1),
intraperitoneally [i.p.]) and C-LNCs (10 mg kg(-1), i.p.) during 6 days, with the
results showing that these treatments significantly attenuated the parasitaemia.
Infected untreated rats showed protein peroxidation and an increase of
nitrites/nitrates, whereas animals treated with curcumin showed a reduction on
these variables. As a result, the activity of antioxidant enzymes (superoxide
dismutase and catalase) differs between groups (P<0.05). Infected animals and
treated with CURC exhibited a reduction in the levels of alanine aminotransferase
and creatinine, when compared with the positive control group. The use of
curcumin in vitro resulted in a better parasitaemia control, an antioxidant
activity and a protective effect on liver and kidney functions of T. evansi
infected adult male Wistar rats.
PMID- 25137644
TI - Healthcare system and the wealth-health gradient: a comparative study of older
populations in six countries.
AB - The present study provides a comparative analysis of the association between
wealth and health in six healthcare systems (Sweden, the United Kingdom, Germany,
the Czech Republic, Israel, the United States). National samples of individuals
fifty years and over reveal considerable cross-country variations in health
outcomes. In all six countries wealth and health are positively associated. The
findings also show that state-based healthcare systems produce better population
health outcomes than private-based healthcare systems. The results indicate that
in five out of the six countries studied, the wealth-health gradients were
remarkably similar, despite significant variations in healthcare system type.
Only in the United States was the association between wealth and health
substantially different from, and much greater than that in the other five
countries. The findings suggest that private-based healthcare system in the U.S.
is likely to promote stronger positive associations between wealth and health.
PMID- 25137645
TI - Perceived quality of an alternative to acute hospitalization: an analytical study
at a community hospital in Hallingdal, Norway.
AB - There is growing international interest in the geography of health care
provision, with health care providers searching for alternatives to acute
hospitalization. In Norway, the government has recently legislated for municipal
authorities to develop local health services for a selected group of patients,
with a quality equal to or better than that provided by hospitals for emergency
admissions. General practitioners in Hallingdal, a rural district in southern
Norway, have for several years referred acutely somatically ill patients to a
community hospital, Hallingdal sjukestugu (HSS). This article analyzes patients'
perceived quality of HSS to demonstrate factors applicable nationally and
internationally to aid in the development of local alternatives to general
hospitals. We used a mixed-methods approach with questionnaires, individual
interviews and a focus group interview. Sixty patients who were taking part in a
randomized, controlled study of acute admissions at HSS answered the
questionnaire. Selected patients were interviewed about their experiences and a
focus group interview was conducted with representatives of local authorities,
administrative personnel and health professionals. Patients admitted to HSS
reported statistically significant greater satisfaction with several care aspects
than those admitted to the general hospital. Factors highlighted by the patients
were the quiet and homelike atmosphere; a small facility which allowed them a
good overall view of the unit; close ties to the local community and continuity
in the patient-staff relationship. The focus group members identified some
overarching factors: an interdisciplinary and holistic approach, local ownership,
proximity to local general practices and close cooperation with the specialist
health services at the hospital. Most of these factors can be viewed as general
elements relevant to the development of local alternatives to acute
hospitalization both nationally and internationally. This study indicates that
perceived quality should be one of the main motivations for developing
alternatives to general hospital admissions.
PMID- 25137646
TI - Enrolment of older people in social health protection programs in West Africa-
does social exclusion play a part?
AB - Although the population of older people in Africa is increasing, and older people
are becoming increasingly vulnerable due to urbanisation, breakdown of family
structures and rising healthcare costs, most African countries have no social
health protection for older people. Two exceptions include Senegal's Plan Sesame,
a user fees exemption for older people and Ghana's National Health Insurance
Scheme (NHIS) where older people are exempt from paying premiums. Evidence on
whether older people are aware of and enrolling in these schemes is however
lacking. We aim to fill this gap. Besides exploring economic indicators, we also
investigate whether social exclusion determines enrolment of older people. This
is the first study that tries to explore the social, political, economic and
cultural (SPEC) dimensions of social exclusion in the context of social health
protection programs for older people. Data were collected by two cross-sectional
household surveys conducted in Ghana and Senegal in 2012. We develop SPEC indices
and conduct logistic regressions to study the determinants of enrolment. Our
results indicate that older people vulnerable to social exclusion in all SPEC
dimensions are less likely to enrol in Plan Sesame and those that are vulnerable
in the political dimension are less likely to enrol in NHIS. Efforts should be
taken to specifically enrol older people in rural areas, ethnic minorities, women
and those isolated due to a lack of social support. Consideration should also be
paid to modify scheme features such as eliminating the registration fee for older
people in NHIS and creating administration offices for ID cards in remote
communities in Senegal.
PMID- 25137647
TI - Discovery of high affinity ligands for beta2-adrenergic receptor through
pharmacophore-based high-throughput virtual screening and docking.
AB - Novel high affinity compounds for human beta2-adrenergic receptor (beta2-AR) were
searched among the clean drug-like subset of ZINC database consisting of
9,928,465 molecules that satisfy the Lipinski's rule of five. The screening
protocol consisted of a high-throughput pharmacophore screening followed by an
extensive amount of docking and rescoring. The pharmacophore model was composed
of key features shared by all five inactive states of beta2-AR in complex with
inverse agonists and antagonists. To test the discriminatory power of the
pharmacophore model, a small-scale screening was initially performed on a
database consisting of 117 compounds of which 53 antagonists were taken as active
inhibitors and 64 agonists as inactive inhibitors. Accordingly, 7.3% of the ZINC
database subset (729,413 compounds) satisfied the pharmacophore requirements,
along with 44 antagonists and 17 agonists. Afterwards, all these hit compounds
were docked to the inactive apo form of the receptor using various docking and
scoring protocols. Following each docking experiment, the best pose was further
evaluated based on the existence of key residues for antagonist binding in its
vicinity. After final evaluations based on the human intestinal absorption (HIA)
and the blood brain barrier (BBB) penetration properties, 62 hit compounds have
been clustered based on their structural similarity and as a result four
scaffolds were revealed. Two of these scaffolds were also observed in three high
affinity compounds with experimentally known Ki values. Moreover, novel chemical
compounds with distinct structures have been determined as potential beta2-AR
drug candidates.
PMID- 25137648
TI - Psychological distress and risk of peripheral vascular disease, abdominal aortic
aneurysm, and heart failure: pooling of sixteen cohort studies.
AB - OBJECTIVES: Examine the little-tested relation of psychological distress with
peripheral vascular disease, abdominal aortic aneurysm, and heart failure.
METHODS: Pooling of raw data from 166,631 male and female participants in 16 UK
based cohort studies. Psychological distress was measured using the 12-item
General Health Questionnaire. Peripheral vascular disease, abdominal aortic
aneurysm, and heart failure events were based on death register linkage. RESULTS:
During a mean follow-up 9.5 years there were 17,368 deaths of which 8625 were
cardiovascular disease-related. Relative to the asymptomatic group (0 score), the
highly distressed group (score 7-12) experienced an elevated risk of peripheral
vascular disease (adjusted hazard ratio; 95% confidence interval: 3.39; 1.97,
5.82) and heart failure (1.76; 1.37, 2.26). Psychological distress was weakly
related to the risk of death from abdominal aortic aneurysm. As anticipated,
distress was associated with cardiovascular disease, coronary heart disease, and
all strokes combined. CONCLUSIONS: In the present study, we provide new evidence
of mental health-related cardiovascular disease presentations.
PMID- 25137651
TI - Quantification of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) in
meconium for detection of alcohol abuse during pregnancy: Correlation study
between both biomarkers.
AB - This article presents results from 47 meconium samples, which were analyzed for
fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) for detection of
gestational alcohol consumption. A validated microwave assisted extraction (MAE)
method in combination with GC-MS developed in the Institute of Forensic Science
(Santiago de Compostela) was used for FAEE and the cumulative concentration of
ethyl myristate, ethyl palmitate and ethyl stearate with a cut-off of 600ng/g was
applied for interpretation. A simple method for identification and quantification
of EtG has been evaluated by ultrasonication followed solid phase extraction
(SPE). Successful validation parameters were obtained for both biochemical
markers of alcohol intake. FAEE and EtG concentrations in meconium ranged between
values lower than LOD and 32,892ng/g or 218ng/g respectively. We have analyzed
FAEE and EtG in the same meconium aliquot, enabling comparison of the efficiency
of gestational ethanol exposure detection. Certain agreement between the two
biomarkers was found as they are both a very specific alcohol markers, making it
a useful analysis for confirmation.
PMID- 25137652
TI - An activity-integrated strategy involving ultra-high-performance liquid
chromatography/quadrupole-time-of-flight mass spectrometry and fraction collector
for rapid screening and characterization of the alpha-glucosidase inhibitors in
Coptis chinensis Franch. (Huanglian).
AB - An activity integrated strategy was established and validated to screen alpha
glucosidase inhibitors by ultra-high-performance liquid chromatography/quadrupole
time-of-flight mass spectrometry and fraction collector (UHPLC/Q-TOF-MS-FC).
UHPLC was used to separate the components in Coptis chinensis Franch. (Huanglian
in Chinese) extract, which was identified by UHPLC-Q-TOF-MS to acquire structural
information and collected by the fraction collector. Finally, the collected
fractions were tested for inhibitory activity of alpha-glucosidase. The results
showed that Huanglian extract had the alpha-glucosidase inhibitory activity with
the IC50 value at 3.528mg mL(-1), which could be used for the treatment of
diabetes. Alkaloids were the main components that had inhibitory activity of
alpha-glucosidase in Huanglian extract, while the inhibitory activity of phenolic
acids against alpha-glucosidase was relatively weaker. Coptisine, epiberberine,
jatrorrhizin and berberine were screened and identified as alpha-glucosidase
inhibitors from Huanglian extract in vitro. Compared with conventional methods,
the integrated UHPLC/Q-TOF-MS-FC method could quantitatively analyze alpha
glucosidase inhibitory activity of individual constituent and provide the total
alpha-glucosidase inhibitory activity of the samples. The results demonstrated
that the activity integrated UHPLC/Q-TOF-MS-FC method was an effective and
powerful tool for screening and identifying active ingredients from Traditional
Chinese medicines.
PMID- 25137653
TI - Development of an improved ligand exchange chiral stationary phase based on
leucinol for the resolution of proton pump inhibitors.
AB - As an effort to develop improved ligand exchange chiral stationary phases (CSPs)
for the resolution of chiral drugs, the residual silanol groups on the silica
surface of a CSP based on sodium N-[(S)-1-hydroxymethyl-3-methylbutyl]-N
undecylaminoacetate, a (S)-leucinol derivative, were protected with n-octyl
groups. The residual silanol group-protected CSP was applied to the resolution of
proton pump inhibitors (PPIs) such as omeprazole, pantoprazole, lansoprazole and
rabeprazole. The resolution of PPIs on the residual silanol group-protected CSP
was excellent with the separation factors (alpha) in the range of 4.32-6.42 and
the resolution factors (RS) in the range of 6.70-7.15. The improved chiral
recognition ability of the residual silanol group-protected CSP was rationalized
to be originated from the protection of the non-enantioselective interaction
sites on the silica surface and the improved lipophilicity of the stationary
phase.
PMID- 25137654
TI - Does nature have joints worth carving? A discussion of taxometrics, model-based
clustering and latent variable mixture modeling.
AB - Taxometric procedures, model-based clustering and latent variable mixture
modeling (LVMM) are statistical methods that use the inter-relationships of
observed symptoms or questionnaire items to investigate empirically whether the
underlying psychiatric or psychological construct is dimensional or categorical.
In this review we show why the results of such an investigation depend on the
characteristics of the observed symptoms (e.g. symptom prevalence in the sample)
and of the sample (e.g. clinical, population sample). Furthermore, the three
methods differ with respect to their assumptions and therefore require different
types of a priori knowledge about the observed symptoms and their inter
relationships. We argue that the choice of method should optimally match and make
use of the existing knowledge about the data that are analyzed.
PMID- 25137658
TI - Contribution of contrast-enhanced ultrasound with Sonovue to describe the
microvascularization of uterine fibroid tumors before and after uterine artery
embolization.
AB - OBJECTIVE: The principal objective of this study was to use contrast-enhanced
ultrasonography to describe the characteristics of fibroid microvascularization
before and after embolization. STUDY DESIGN: Forty women had contrast-enhanced
ultrasonography with Sonovue((r)) injections before uterine artery embolization,
the day afterwards, and at 6-12 months afterwards. An MRI was also performed
before and after the procedure. RESULTS: Two thirds of the fibroids took up the
contrast product before the myometrium did, and 45.8% were vascularized along the
peripheral rim of the fibroid, compared with 41.6% with a principal pedicle and
from the center in three (12.6%). After embolization at day one (D1), the
myometrium was fully enhanced, that is, perfusion of the myometrium was plainly
visible, in 25 cases (69.4%; n=36), partially enhanced in eight (22.2%), and
totally avascular in three (8.4%). Analysis of the failures according to imaging
criteria the day after embolization (D1) showed failure in seven women, with
partial enhancement for six, and total for one. In the imaging at 6 months (M6),
contrast ultrasonography showed failure for three women, with enhancement of the
largest fibroid. This enhancement was total in two cases and partial (40%) in
one. There were five failures according to MRI at M6, with partial enhancement.
Only two of these failures were simultaneously failures according to the contrast
enhanced ultrasonography. There were five clinical failures, two consistent with
the imaging at 6 months and four predictable on D1. CONCLUSION: Contrast-enhanced
ultrasonography is feasible and useful to understand fibroid vascularization and
for monitoring embolization; its correlation with MRI is good, its concordance
less so.
PMID- 25137659
TI - Simply avoiding reactivating fear memory after exposure therapy may help to
consolidate fear extinction memory--a reply.
PMID- 25137673
TI - Synergetic gating of metal-latching ligands and metal-chelating proteins for
mesoporous silica nanovehicles to enhance delivery efficiency.
AB - Stimuli-responsive drug delivery systems are highly desirable for improved
therapeutic efficacy and minimized adverse effects of drugs. Mesoporous silica
nanoparticles (MSNs) functionalized with pentadentate ligands, N-(3
trimethoxysilylpropyl)ethylenediamine triacetate (TSP-DATA), in the presence of
metal ions with and without myoglobin (Mb)-containing surface-accessible
histidine residues, were constructed for pH-triggered controlled release. The
DATA ligands immobilized on the MSN pore outlets could encapsulate cargo within
the pores by metal latching across pore openings, and release efficiency
increased with the increase of surface density of the DATA ligands. The release
efficiencies for the metal-chelating protein nanogates, through multiple-site
binding of Mb with the metal-chelating ligands, were higher than those for the
metal-latching ligand nanogates but were almost independent of surface density of
the ligands investigated. Both the metal-latching ligands and the metal-chelating
proteins played a synergetic role in gating MSNs for high-loading drug delivery
and stimuli-responsive controlled release. The constructed Mb-Cu(2+)-gated MSN
delivery system has promising applications in targeted drug therapy of tumors.
PMID- 25137681
TI - Uncertainty representation of grey numbers and grey sets.
AB - In the literature, there is a presumption that a grey set and an interval-valued
fuzzy set are equivalent. This presumption ignores the existence of discrete
components in a grey number. In this paper, new measurements of uncertainties of
grey numbers and grey sets, consisting of both absolute and relative
uncertainties, are defined to give a comprehensive representation of
uncertainties in a grey number and a grey set. Some simple examples are provided
to illustrate that the proposed uncertainty measurement can give an effective
representation of both absolute and relative uncertainties in a grey number and a
grey set. The relationships between grey sets and interval-valued fuzzy sets are
also analyzed from the point of view of the proposed uncertainty representation.
The analysis demonstrates that grey sets and interval-valued fuzzy sets provide
different but overlapping models for uncertainty representation in sets.
PMID- 25137674
TI - Fluorinated polyimide gate dielectrics for the advancing the electrical stability
of organic field-effect transistors.
AB - Organic field-effect transistors (OFETs) that operated with good electrical
stability were prepared by synthesizing fluorinated polyimide (PI) gate
dielectrics based on 6FDA-PDA-PDA PI and 6FDA-CF3Bz-PDA PI. 6FDA-PDA-PDA PI and
6FDA-CF3Bz-PDA PI contain 6 and 18 fluorine atoms per repeat unit, respectively.
These fluorinated polymers provided smooth surface topographies and surface
energies that decreased as the number of fluorine atoms in the polymer backbone
increased. These properties led to a better crystalline morphology in the
semiconductor film grown over their surfaces. The number of fluorine atoms in the
PI backbone increased, the field-effect mobility improved, and the threshold
voltage shifted toward positive values (from -0.38 to +2.21 V) in the OFETs with
pentacene and triethylsilylethynyl anthradithiophene. In addition, the highly
fluorinated polyimide dielectric showed negligible hysteresis and a notable gate
bias stability under both a N2 environment and ambient air.
PMID- 25137682
TI - Distributed finite-time containment control for double-integrator multiagent
systems.
AB - In this paper, the distributed finite-time containment control problem for double
integrator multiagent systems with multiple leaders and external disturbances is
discussed. In the presence of multiple dynamic leaders, by utilizing the
homogeneous control technique, a distributed finite-time observer is developed
for the followers to estimate the weighted average of the leaders' velocities at
first. Then, based on the estimates and the generalized adding a power integrator
approach, distributed finite-time containment control algorithms are designed to
guarantee that the states of the followers converge to the dynamic convex hull
spanned by those of the leaders in finite time. Moreover, as a special case of
multiple dynamic leaders with zero velocities, the proposed containment control
algorithms also work for the case of multiple stationary leaders without using
the distributed observer. Simulations demonstrate the effectiveness of the
proposed control algorithms.
PMID- 25137683
TI - Community-aware task allocation for social networked multiagent systems.
AB - In this paper, we propose a novel community-aware task allocation model for
social networked multiagent systems (SN-MASs), where the agent' cooperation
domain is constrained in community and each agent can negotiate only with its
intracommunity member agents. Under such community-aware scenarios, we prove that
it remains NP-hard to maximize system overall profit. To solve this problem
effectively, we present a heuristic algorithm that is composed of three phases:
1) task selection: select the desirable task to be allocated preferentially; 2)
allocation to community: allocate the selected task to communities based on a
significant task-first heuristics; and 3) allocation to agent: negotiate
resources for the selected task based on a nonoverlap agent-first and breadth
first resource negotiation mechanism. Through the theoretical analyses and
experiments, the advantages of our presented heuristic algorithm and community
aware task allocation model are validated. 1) Our presented heuristic algorithm
performs very closely to the benchmark exponential brute-force optimal algorithm
and the network flow-based greedy algorithm in terms of system overall profit in
small-scale applications. Moreover, in the large-scale applications, the
presented heuristic algorithm achieves approximately the same overall system
profit, but significantly reduces the computational load compared with the greedy
algorithm. 2) Our presented community-aware task allocation model reduces the
system communication cost compared with the previous global-aware task allocation
model and improves the system overall profit greatly compared with the previous
local neighbor-aware task allocation model.
PMID- 25137684
TI - Hyperspectral image classification using functional data analysis.
AB - The large number of spectral bands acquired by hyperspectral imaging sensors
allows us to better distinguish many subtle objects and materials. Unlike other
classical hyperspectral image classification methods in the multivariate analysis
framework, in this paper, a novel method using functional data analysis (FDA) for
accurate classification of hyperspectral images has been proposed. The central
idea of FDA is to treat multivariate data as continuous functions. From this
perspective, the spectral curve of each pixel in the hyperspectral images is
naturally viewed as a function. This can be beneficial for making full use of the
abundant spectral information. The relevance between adjacent pixel elements in
the hyperspectral images can also be utilized reasonably. Functional principal
component analysis is applied to solve the classification problem of these
functions. Experimental results on three hyperspectral images show that the
proposed method can achieve higher classification accuracies in comparison to
some state-of-the-art hyperspectral image classification methods.
PMID- 25137685
TI - A new design of robust Hinfinity sliding mode control for uncertain stochastic T
S fuzzy time-delay systems.
AB - In this paper, a novel dynamic sliding mode control scheme is proposed for a
class of uncertain stochastic nonlinear time-delay systems represented by Takagi
Sugeno fuzzy models. The key advantage of the proposed scheme is that two very
restrictive assumptions in most existing sliding mode control approaches for
stochastic fuzzy systems have been removed. It is shown that the closed-loop
control system trajectories can be driven onto the sliding surface in finite time
almost certainly. It is also shown that the stochastic stability of the resulting
sliding motion can be guaranteed in terms of linear matrix inequalities;
moreover, the sliding-mode controller can be obtained simultaneously. Simulation
results illustrating the advantages and effectiveness of the proposed approaches
are also provided.
PMID- 25137686
TI - Bare bones particle swarm optimization with scale matrix adaptation.
AB - Bare bones particle swarm optimization (BBPSO) is a swarm algorithm that has
shown potential for solving single-objective unconstrained optimization problems
over continuous search spaces. However, it suffers of the premature convergence
problem that means it may get trapped into a local optimum when solving
multimodal problems. In order to address this drawback and improve the
performance of the BBPSO, we propose a variant of this algorithm, named by us as
BBPSO with scale matrix adaptation (SMA), SMA-BBPSO for short reference. In the
SMA-BBPSO, the position of a particle is selected from a multivariate t
distribution with a rule for adaptation of its scale matrix. We use the
multivariate t-distribution in its hierarchical form, as a scale mixtures of
normal distributions. The t -distribution has heavier tails than those of the
normal distribution, which increases the ability of the particles to escape from
a local optimum. In addition, our approach includes the normal distribution as a
particular case. As a consequence, the t -distribution can be applied during the
optimization process by maintaining the proper balance between exploration and
exploitation. We also propose a simple update rule to adapt the scale matrix
associated with a particle. Our strategy consists of adapting the scale matrix of
a particle such that the best position found by any particle in its neighborhood
is sampled with maximum likelihood in the next iteration. A theoretical analysis
was developed to explain how the SMA-BBPSO works, and an empirical study was
carried out to evaluate the performance of the proposed algorithm. The
experimental results show the suitability of the proposed approach in terms of
effectiveness to find good solutions for all benchmark problems investigated.
Nonparametric statistical tests indicate that SMA-BBPSO shows a statistically
significant improvement compared with other swarm algorithms.
PMID- 25137687
TI - Exposure fusion using boosting Laplacian pyramid.
AB - This paper proposes a new exposure fusion approach for producing a high quality
image result from multiple exposure images. Based on the local weight and global
weight by considering the exposure quality measurement between different exposure
images, and the just noticeable distortion-based saliency weight, a novel hybrid
exposure weight measurement is developed. This new hybrid weight is guided not
only by a single image's exposure level but also by the relative exposure level
between different exposure images. The core of the approach is our novel boosting
Laplacian pyramid, which is based on the structure of boosting the detail and
base signal, respectively, and the boosting process is guided by the proposed
exposure weight. Our approach can effectively blend the multiple exposure images
for static scenes while preserving both color appearance and texture structure.
Our experimental results demonstrate that the proposed approach successfully
produces visually pleasing exposure fusion images with better color appearance
and more texture details than the existing exposure fusion techniques and tone
mapping operators.
PMID- 25137688
TI - Acquisition of causal models for local distributions in Bayesian networks.
AB - To specify a Bayesian network, a local distribution in the form of a conditional
probability table, often of an effect conditioned on its n causes, needs to be
acquired, one for each non-root node. Since the number of parameters to be
assessed is generally exponential in n , improving the efficiency is an important
concern in knowledge engineering. Non-impeding noisy-AND (NIN-AND) tree causal
models reduce the number of parameters to being linear in n , while explicitly
expressing both reinforcing and undermining interactions among causes. The key
challenge in NIN-AND tree modeling is the acquisition of the NIN-AND tree
structure. In this paper, we formulate a concise structure representation and an
expressive causal interaction function of NIN-AND trees. Building on these
representations, we propose two structural acquisition methods, which are
applicable to both elicitation-based and machine learning-based acquisitions.
Their accuracy is demonstrated through experimental evaluations.
PMID- 25137689
TI - Sensor-driven area coverage for an autonomous fixed-wing unmanned aerial vehicle.
AB - Area coverage with an onboard sensor is an important task for an unmanned aerial
vehicle (UAV) with many applications. Autonomous fixed-wing UAVs are more
appropriate for larger scale area surveying since they can cover ground more
quickly. However, their non-holonomic dynamics and susceptibility to disturbances
make sensor coverage a challenging task. Most previous approaches to area
coverage planning are offline and assume that the UAV can follow the planned
trajectory exactly. In this paper, this restriction is removed as the aircraft
maintains a coverage map based on its actual pose trajectory and makes control
decisions based on that map. The aircraft is able to plan paths in situ based on
sensor data and an accurate model of the on-board camera used for coverage. An
information theoretic approach is used that selects desired headings that
maximize the expected information gain over the coverage map. In addition, the
branch entropy concept previously developed for autonomous underwater vehicles is
extended to UAVs and ensures that the vehicle is able to achieve its global
coverage mission. The coverage map over the workspace uses the projective camera
model and compares the expected area of the target on the ground and the actual
area covered on the ground by each pixel in the image. The camera is mounted on a
two-axis gimbal and can either be stabilized or optimized for maximal coverage.
Hardware-in-the-loop simulation results and real hardware implementation on a
fixed-wing UAV show the effectiveness of the approach. By including the already
developed automatic takeoff and landing capabilities, we now have a fully
automated and robust platform for performing aerial imagery surveys.
PMID- 25137690
TI - DEC: dynamically evolving clustering and its application to structure
identification of evolving fuzzy models.
AB - Identification of models from input-output data essentially requires estimation
of appropriate cluster centers. In this paper, a new online evolving clustering
approach for streaming data is proposed. Unlike other approaches that consider
either the data density or distance from existing cluster centers, this approach
uses cluster weight and distance before generating new clusters. To capture the
dynamics of the data stream, the cluster weight is defined in both data and time
space in such a way that it decays exponentially with time. It also applies
concepts from computational geometry to determine the neighborhood information
while forming clusters. A distinction is made between core and noncore clusters
to effectively identify the real outliers. The approach efficiently estimates
cluster centers upon which evolving Takagi-Sugeno models are developed. The
experimental results with developed models show that the proposed approach
attains results at par or better than existing approaches and significantly
reduces the computational overhead, which makes it suitable for real-time
applications.
PMID- 25137691
TI - A generic method for the evaluation of interval type-2 fuzzy linguistic
summaries.
AB - Linguistic summarization has turned out to be an important knowledge discovery
technique by providing the most relevant natural language-based sentences in a
human consistent manner. While many studies on linguistic summarization have
handled ordinary fuzzy sets [type-1 fuzzy set (T1FS)] for modeling words, only
few of them have dealt with interval type-2 fuzzy sets (IT2FS) even though IT2FS
is better capable of handling uncertainties associated with words. Furthermore,
the existent studies work with the scalar cardinality based degree of truth which
might lead to inconsistency in the evaluation of interval type-2 fuzzy (IT2F)
linguistic summaries. In this paper, to overcome this shortcoming, we propose a
novel probabilistic degree of truth for evaluating IT2F linguistic summaries in
the forms of type-I and type-II quantified sentences. We also extend the
properties that should be fulfilled by any degree of truth on linguistic
summarization with T1FS to IT2F environment. We not only prove that our
probabilistic degree of truth satisfies the given properties, but also illustrate
by examples that it provides more consistent results when compared to the
existing degree of truth in the literature. Furthermore, we carry out an
application on linguistic summarization of time series data of Europe Brent Spot
Price, along with a comparison of the results achieved with our approach and that
of the existing degree of truth in the literature.
PMID- 25137692
TI - Generalized Laplacian eigenmaps for modeling and tracking human motions.
AB - This paper presents generalized Laplacian eigenmaps, a novel dimensionality
reduction approach designed to address stylistic variations in time series. It
generates compact and coherent continuous spaces whose geometry is data-driven.
This paper also introduces graph-based particle filter, a novel methodology
conceived for efficient tracking in low dimensional space derived from a spectral
dimensionality reduction method. Its strengths are a propagation scheme, which
facilitates the prediction in time and style, and a noise model coherent with the
manifold, which prevents divergence, and increases robustness. Experiments show
that a combination of both techniques achieves state-of-the-art performance for
human pose tracking in underconstrained scenarios.
PMID- 25137693
TI - Maximal entropy random walk for region-based visual saliency.
AB - Visual saliency is attracting more and more research attention since it is
beneficial to many computer vision applications. In this paper, we propose a
novel bottom-up saliency model for detecting salient objects in natural images.
First, inspired by the recent advance in the realm of statistical thermodynamics,
we adopt a novel mathematical model, namely, the maximal entropy random walk
(MERW) to measure saliency. We analyze the rationality and superiority of MERW
for modeling visual saliency. Then, based on the MERW model, we establish a
generic framework for saliency detection. Different from the vast majority of
existing saliency models, our method is built on a purely region-based strategy,
which is able to yield high-resolution saliency maps with well preserved object
shapes and uniformly highlighted salient regions. In the proposed framework, the
input image is first over-segmented into superpixels, which are taken as the
primary units for subsequent procedures, and regional features are extracted.
Then, saliency is measured according to two principles, i.e., uniqueness and
visual organization, both implemented in a unified approach, i.e., the MERW model
based on graph representation. Intensive experimental results on publicly
available datasets demonstrate that our method outperforms the state-of-the-art
saliency models.
PMID- 25137694
TI - Significant body point labeling and tracking.
AB - In this paper, a method is presented to label and track anatomical landmarks
(e.g., head, hand/arm, feet), which are referred to as significant body points
(SBPs), using implicit body models. By considering the human body as an inverted
pendulum model, ellipse fitting and contour moments are applied to classify it as
being in Stand, Sit, or Lie posture. A convex hull of the silhouette contour is
used to determine the locations of SBPs. The particle filter or a motion flow
based method is used to predict SBPs in occlusion. Stick figures of various
activities are generated by connecting the SBPs. The qualitative and quantitative
evaluation show that the proposed method robustly labels and tracks SBPs in
various activities of two different (low and high) resolution data sets.
PMID- 25137695
TI - A framework for biodynamic feedthrough analysis--part II: validation and
application.
AB - Biodynamic feedthrough (BDFT) is a complex phenomenon, that has been studied for
several decades. However, there is little consensus on how to approach the BDFT
problem in terms of definitions, nomenclature, and mathematical descriptions. In
this paper, the framework for BDFT analysis, as presented in Part I of this dual
publication, is validated and applied. The goal of this framework is twofold.
First of all, it provides some common ground between the seemingly large range of
different approaches existing in BDFT literature. Secondly, the framework itself
allows for gaining new insights into BDFT phenomena. Using recently obtained
measurement data, parts of the framework that were not already addressed
elsewhere, are validated. As an example of a practical application of the
framework, it will be demonstrated how the effects of control device dynamics on
BDFT can be understood and accurately predicted. Other ways of employing the
framework are illustrated by interpreting the results of three selected studies
from the literature using the BDFT framework. The presentation of the BDFT
framework is divided into two parts. This paper, Part II, addresses the
validation and application of the framework. Part I, which is also published in
this journal issue, addresses the theoretical foundations of the framework. The
work is presented in two separate papers to allow for a detailed discussion of
both the framework's theoretical background and its validation.
PMID- 25137718
TI - High-resolution mesoscopic fluorescence molecular tomography based on compressive
sensing.
AB - Mesoscopic fluorescence molecular tomography (MFMT) is new imaging modality
aiming at 3-D imaging of molecular probes in a few millimeter thick biological
samples with high-spatial resolution. In this paper, we develop a compressive
sensing-based reconstruction method with l1-norm regularization for MFMT with the
goal of improving spatial resolution and stability of the optical inverse
problem. Three-dimensional numerical simulations of anatomically accurate
microvasculature and real data obtained from phantom experiments are employed to
evaluate the merits of the proposed method. Experimental results show that the
proposed method can achieve 80 MUm spatial resolution for a biological sample of
3 mm thickness and more accurate quantifications of concentrations and locations
for the fluorophore distribution than those of the conventional methods.
PMID- 25137719
TI - Novel active comb-shaped dry electrode for EEG measurement in hairy site.
AB - Electroencephalography (EEG) is an important biopotential, and has been widely
applied in clinical applications. The conventional EEG electrode with conductive
gels is usually used for measuring EEG. However, the use of conductive gel also
encounters with the issue of drying and hardening. Recently, many dry EEG
electrodes based on different conductive materials and techniques were proposed
to solve the previous issue. However, measuring EEG in the hairy site is still a
difficult challenge. In this study, a novel active comb-shaped dry electrode was
proposed to measure EEG in hairy site. Different form other comb-shaped or spike
shaped dry electrodes, it can provide more excellent performance of avoiding the
signal attenuation, phase distortion, and the reduction of common mode rejection
ratio. Even under walking motion, it can effectively acquire EEG in hairy site.
Finally, the experiments for alpha rhythm and steady-state visually evoked
potential were also tested to validate the proposed electrode.
PMID- 25137720
TI - Motion artifacts in capacitive ECG measurements: reducing the combined effect of
DC voltages and capacitance changes using an injection signal.
AB - Capacitive electrodes are a promising alternative to the conventional adhesive
electrodes for ECG measurements. They provide more comfort to the patient when
integrated in everyday objects (e.g., beds or seats) for long-term monitoring.
However, the application of capacitive sensors is limited by their high
sensitivity to motion artifacts. For example, motion at the body-electrode
interface causes variations of the coupling capacitance which, in the presence of
a dc voltage across the coupling capacitor, create strong artifacts in the
measurements. The origin, relevance, and reduction of this specific and important
type of artifacts are studied here. An injection signal is exploited to track the
variations of the coupling capacitance in real time. This information is then
used by an identification scheme to estimate the artifacts and subtract them from
the measurements. The method was evaluated in simulations, lab environments, and
in a real-life recording on an adult's chest. For the type of artifact under
study, a strong artifact reduction ranging from 40 dB for simulated data to 9 dB
for a given real-life recording was achieved. The proposed method is automated,
does not require any knowledge about the measurement system parameters, and
provides an online estimate for the dc voltage across the coupling capacitor.
PMID- 25137721
TI - Four-class classification of skin lesions with task decomposition strategy.
AB - This paper proposes a new computer-aided method for the skin lesion
classification applicable to both melanocytic skin lesions (MSLs) and
nonmelanocytic skin lesions (NoMSLs). The computer-aided skin lesion
classification has drawn attention as an aid for detection of skin cancers.
Several researchers have developed methods to distinguish between melanoma and
nevus, which are both categorized as MSL. However, most of these studies did not
focus on NoMSLs such as basal cell carcinoma (BCC), the most common skin cancer
and seborrheic keratosis (SK) despite their high incidence rates. It is
preferable to deal with these NoMSLs as well as MSLs especially for the potential
users who are not enough capable of diagnosing pigmented skin lesions on their
own such as dermatologists in training and physicians with different expertise.
We developed a new method to distinguish among melanomas, nevi, BCCs, and SKs.
Our method calculates 828 candidate features grouped into three categories:
color, subregion, and texture. We introduced two types of classification models:
a layered model that uses a task decomposition strategy and flat models to serve
as performance baselines. We tested our methods on 964 dermoscopy images: 105
melanomas, 692 nevi, 69 BCCs, and 98 SKs. The layered model outperformed the flat
models, achieving detection rates of 90.48%, 82.51%, 82.61%, and 80.61% for
melanomas, nevi, BCCs, and SKs, respectively. We also identified specific
features effective for the classification task including irregularity of color
distribution. The results show promise for enhancing the capability of the
computer-aided skin lesion classification.
PMID- 25137722
TI - Identifying Virtual 3D Geometric Shapes with a Vibrotactile Glove.
AB - The emergence of off-screen interaction devices is bringing the field of virtual
reality to a broad range of applications where virtual objects can be manipulated
without the use of traditional peripherals. However, to facilitate object
interaction, other stimuli such as haptic feedback are necessary to improve the
user experience. To enable the identification of virtual 3D objects without
visual feedback, a haptic display based on a vibrotactile glove and multiple
points of contact gives users an enhanced sensation of touching a virtual object
with their hands. Experimental results demonstrate the capacity of this
technology in practical applications.
PMID- 25137724
TI - A Tool-Free Calibration Method for Turntable-Based 3D Scanning Systems.
AB - Turntable-based 3D scanners are popular but require calibration of the turntable
axis. Existing methods for turntable calibration typically make use of specially
designed tools, such as a chessboard or criterion sphere, which users must
manually install and dismount. In this article, the authors propose an automatic
method to calibrate the turntable axis without any calibration tools. Given a
scan sequence of the input object, they first recover the initial rotation axis
from an automatic registration step. Then they apply an iterative procedure to
obtain the optimized turntable axis. This iterative procedure alternates between
two steps: refining the initial pose of the input scans and approximating the
rotation matrix. The performance of the proposed method was evaluated on a
structured light-based scanning system.
PMID- 25137723
TI - Visualization beyond the desktop--the next big thing.
AB - Visualization is coming of age. With visual depictions being seamlessly
integrated into documents, and data visualization techniques being used to
understand increasingly large and complex datasets, the term "visualization"' is
becoming used in everyday conversations. But we are on a cusp; visualization
researchers need to develop and adapt to today's new devices and tomorrow's
technology. Today, people interact with visual depictions through a mouse.
Tomorrow, they'll be touching, swiping, grasping, feeling, hearing, smelling, and
even tasting data. The next big thing is multisensory visualization that goes
beyond the desktop.
PMID- 25137725
TI - Automated segmentation of breast in 3-D MR images using a robust atlas.
AB - This paper presents a robust atlas-based segmentation (ABS) algorithm for
segmentation of the breast boundary in 3-D MR images. The proposed algorithm
combines the well-known methodologies of ABS namely probabilistic atlas and atlas
selection approaches into a single framework where two configurations are
realized. The algorithm uses phase congruency maps to create an atlas which is
robust to intensity variations. This allows an atlas derived from images acquired
with one MR imaging sequence to be used to segment images acquired with a
different MR imaging sequence and eliminates the need for intensity-based
registration. Images acquired using a Dixon sequence were used to create an atlas
which was used to segment both Dixon images (intra-sequence) and T1-weighted
images (inter-sequence). In both cases, highly accurate results were achieved
with the median Dice similarity coefficient values of 94% +/-4% and 87 +/-6.5%,
respectively.
PMID- 25137726
TI - Bias reduction for low-statistics PET: maximum likelihood reconstruction with a
modified Poisson distribution.
AB - Positron emission tomography data are typically reconstructed with maximum
likelihood expectation maximization (MLEM). However, MLEM suffers from positive
bias due to the non-negativity constraint. This is particularly problematic for
tracer kinetic modeling. Two reconstruction methods with bias reduction
properties that do not use strict Poisson optimization are presented and compared
to each other, to filtered backprojection (FBP), and to MLEM. The first method is
an extension of NEGML, where the Poisson distribution is replaced by a Gaussian
distribution for low count data points. The transition point between the Gaussian
and the Poisson regime is a parameter of the model. The second method is a
simplification of ABML. ABML has a lower and upper bound for the reconstructed
image whereas AML has the upper bound set to infinity. AML uses a negative lower
bound to obtain bias reduction properties. Different choices of the lower bound
are studied. The parameter of both algorithms determines the effectiveness of the
bias reduction and should be chosen large enough to ensure bias-free images. This
means that both algorithms become more similar to least squares algorithms, which
turned out to be necessary to obtain bias-free reconstructions. This comes at the
cost of increased variance. Nevertheless, NEGML and AML have lower variance than
FBP. Furthermore, randoms handling has a large influence on the bias.
Reconstruction with smoothed randoms results in lower bias compared to
reconstruction with unsmoothed randoms or randoms precorrected data. However,
NEGML and AML yield both bias-free images for large values of their parameter.
PMID- 25137727
TI - Compressive sensing of sparse tensors.
AB - Compressive sensing (CS) has triggered an enormous research activity since its
first appearance. CS exploits the signal's sparsity or compressibility in a
particular domain and integrates data compression and acquisition, thus allowing
exact reconstruction through relatively few nonadaptive linear measurements.
While conventional CS theory relies on data representation in the form of
vectors, many data types in various applications, such as color imaging, video
sequences, and multisensor networks, are intrinsically represented by higher
order tensors. Application of CS to higher order data representation is typically
performed by conversion of the data to very long vectors that must be measured
using very large sampling matrices, thus imposing a huge computational and memory
burden. In this paper, we propose generalized tensor compressive sensing (GTCS)-a
unified framework for CS of higher order tensors, which preserves the intrinsic
structure of tensor data with reduced computational complexity at reconstruction.
GTCS offers an efficient means for representation of multidimensional data by
providing simultaneous acquisition and compression from all tensor modes. In
addition, we propound two reconstruction procedures, a serial method and a
parallelizable method. We then compare the performance of the proposed method
with Kronecker compressive sensing (KCS) and multiway compressive sensing (MWCS).
We demonstrate experimentally that GTCS outperforms KCS and MWCS in terms of both
reconstruction accuracy (within a range of compression ratios) and processing
speed. The major disadvantage of our methods (and of MWCS as well) is that the
compression ratios may be worse than that offered by KCS.
PMID- 25137728
TI - Topology preserving thinning of cell complexes.
AB - A topology preserving skeleton is a synthetic representation of an object that
retains its topology and many of its significant morphological properties. The
process of obtaining the skeleton, referred to as skeletonization or thinning, is
a very active research area. It plays a central role in reducing the amount of
information to be processed during image analysis and visualization, computer
aided diagnosis, or by pattern recognition algorithms. This paper introduces a
novel topology preserving thinning algorithm, which removes simple cells-a
generalization of simple points-of a given cell complex. The test for simple
cells is based on acyclicity tables automatically produced in advance with
homology computations. Using acyclicity tables render the implementation of
thinning algorithms straightforward. Moreover, the fact that tables are
automatically filled for all possible configurations allows to rigorously prove
the generality of the algorithm and to obtain fool-proof implementations. The
novel approach enables, for the first time, according to our knowledge, to thin a
general unstructured simplicial complex. Acyclicity tables for cubical and
simplicial complexes and an open source implementation of the thinning algorithm
are provided as an additional material to allow their immediate use in the vast
number of applications arising in medical imaging and beyond.
PMID- 25137729
TI - On continuous user authentication via typing behavior.
AB - We hypothesize that an individual computer user has a unique and consistent
habitual pattern of hand movements, independent of the text, while typing on a
keyboard. As a result, this paper proposes a novel biometric modality named
typing behavior (TB) for continuous user authentication. Given a webcam pointing
toward a keyboard, we develop real-time computer vision algorithms to
automatically extract hand movement patterns from the video stream. Unlike the
typical continuous biometrics, such as keystroke dynamics (KD), TB provides a
reliable authentication with a short delay, while avoiding explicit key-logging.
We collect a video database where 63 unique subjects type static text and free
text for multiple sessions. For one typing video, the hands are segmented in each
frame and a unique descriptor is extracted based on the shape and position of
hands, as well as their temporal dynamics in the video sequence. We propose a
novel approach, named bag of multi-dimensional phrases, to match the cross
feature and cross-temporal pattern between a gallery sequence and probe sequence.
The experimental results demonstrate a superior performance of TB when compared
with KD, which, together with our ultrareal-time demo system, warrant further
investigation of this novel vision application and biometric modality.
PMID- 25137730
TI - Time-Varying Ankle Mechanical Impedance During Human Locomotion.
AB - In human locomotion, we continuously modulate joint mechanical impedance of the
lower limb (hip, knee, and ankle) either voluntarily or reflexively to
accommodate environmental changes and maintain stable interaction. Ankle
mechanical impedance plays a pivotal role at the interface between the neuro
mechanical system and the physical world. This paper reports, for the first time,
a characterization of human ankle mechanical impedance in two degrees-of-freedom
simultaneously as it varies with time during walking. Ensemble-based linear time
varying system identification methods implemented with a wearable ankle robot,
Anklebot, enabled reliable estimation of ankle mechanical impedance from the pre
swing phase through the entire swing phase to the early-stance phase. This
included heel-strike and toe-off, key events in the transition from the swing to
stance phase or vice versa. Time-varying ankle mechanical impedance was
accurately approximated by a second order model consisting of inertia, viscosity,
and stiffness in both inversion-eversion and dorsiflexion-plantarflexion
directions, as observed in our previous steady-state dynamic studies. We found
that viscosity and stiffness of the ankle significantly decreased at the end of
the stance phase before toe-off, remained relatively constant across the swing
phase, and increased around heel-strike. Closer investigation around heel-strike
revealed that viscosity and stiffness in both planes increased before heel-strike
occurred. This finding is important evidence of "pretuning" by the central
nervous system. In addition, viscosity and stiffness were greater in the sagittal
plane than in the frontal plane across all subgait phases, except the early
stance phase. Comparison with previous studies and implications for clinical
study of neurologically impaired patients are provided.
PMID- 25137731
TI - An Intelligent Robotic Hospital Bed for Safe Transportation of Critical
Neurosurgery Patients Along Crowded Hospital Corridors.
AB - We present a novel design of an intelligent robotic hospital bed, named Flexbed,
with autonomous navigation ability. The robotic bed is developed for fast and
safe transportation of critical neurosurgery patients without changing beds.
Flexbed is more efficient and safe during the transportation process comparing to
the conventional hospital beds. Flexbed is able to avoid en-route obstacles with
an efficient easy-to-implement collision avoidance strategy when an obstacle is
nearby and to move towards its destination at maximum speed when there is no
threat of collision. We present extensive simulation results of navigation of
Flexbed in the crowded hospital corridor environments with moving obstacles.
Moreover, results of experiments with Flexbed in the real world scenarios are
also presented and discussed.
PMID- 25137732
TI - Feasibility of Energy-Autonomous Wireless Microsensors for Biomedical
Applications: Powering and Communication.
AB - In this review, biomedical-related wireless miniature devices such as implantable
medical devices, neural prostheses, embedded neural systems, and body area
network systems are investigated and categorized. The two main subsystems of such
designs, the RF subsystem and the energy source subsystem, are studied in detail.
Different application classes are considered separately, focusing on their
specific data rate and size characteristics. Also, the energy consumption of
state-of-the-art communication practices is compared to the energy that can be
generated by current energy scavenging devices, highlighting gaps and
opportunities. The RF subsystem is classified, and the suitable architecture for
each category of applications is highlighted. Finally, a new figure of merit
suitable for wireless biomedical applications is introduced to measure the
performance of these devices and assist the designer in selecting the proper
system for the required application. This figure of merit can effectively fill
the gap of a much required method for comparing different techniques in
simulation stage before a final design is chosen for implementation.
PMID- 25137733
TI - Optoelectronic Systems Trained With Backpropagation Through Time.
AB - Delay-coupled optoelectronic systems form promising candidates to act as powerful
information processing devices. In this brief, we consider such a system that has
been studied before in the context of reservoir computing (RC). Instead of
viewing the system as a random dynamical system, we see it as a true machine
learning model, which can be fully optimized. We use a recently introduced
extension of backpropagation through time, an optimization algorithm originally
designed for recurrent neural networks, and use it to let the network perform a
difficult phoneme recognition task. We show that full optimization of all system
parameters of delay-coupled optoelectronics systems yields a significant
improvement over the previously applied RC approach.
PMID- 25137734
TI - Phase Oscillatory Network and Visual Pattern Recognition.
AB - We explore a properly interconnected set of Kuramoto type oscillators that
results in a new associative-memory network configuration, which includes second-
and third-order additional terms in the Fourier expansion of the network's
coupling. Investigation of the response of the network to different external
stimuli indicates an increase in the network capability for coding and
information retrieval. Comparison of the network output with that of an
equivalent experiment with subjects, for recognizing perturbed binary patterns,
shows comparable results between the two approaches. We also discuss the enhanced
storage capacity of the network.
PMID- 25137736
TI - Universal fuzzy models and universal fuzzy controllers for discrete-time
nonlinear systems.
AB - This paper investigates the problems of universal fuzzy model and universal fuzzy
controller for discrete-time nonaffine nonlinear systems (NNSs). It is shown that
a kind of generalized T-S fuzzy model is the universal fuzzy model for discrete
time NNSs satisfying a sufficient condition. The results on universal fuzzy
controllers are presented for two classes of discrete-time stabilizable NNSs.
Constructive procedures are provided to construct the model reference fuzzy
controllers. The simulation example of an inverted pendulum is presented to
illustrate the effectiveness and advantages of the proposed method. These results
significantly extend the approach for potential applications in solving complex
engineering problems.
PMID- 25137737
TI - A new evolutionary algorithm with structure mutation for the maximum balanced
biclique problem.
AB - The maximum balanced biclique problem (MBBP), an NP-hard combinatorial
optimization problem, has been attracting more attention in recent years.
Existing node-deletion-based algorithms usually fail to find high-quality
solutions due to their easy stagnation in local optima, especially when the scale
of the problem grows large. In this paper, a new algorithm for the MBBP,
evolutionary algorithm with structure mutation (EA/SM), is proposed. In the EA/SM
framework, local search complemented with a repair-assisted restart process is
adopted. A new mutation operator, SM, is proposed to enhance the exploration
during the local search process. The SM can change the structure of solutions
dynamically while keeping their size (fitness) and the feasibility unchanged. It
implements a kind of large mutation in the structure space of MBBP to help the
algorithm escape from local optima. An MBBP-specific local search operator is
designed to improve the quality of solutions efficiently; besides, a new repair
assisted restart process is introduced, in which the Marchiori's heuristic repair
is modified to repair every new solution reinitialized by an estimation of
distribution algorithm (EDA)-like process. The proposed algorithm is evaluated on
a large set of benchmark graphs with various scales and densities. Experimental
results show that: 1) EA/SM produces significantly better results than the state
of-the-art heuristic algorithms; 2) it also outperforms a repair-based EDA and a
repair-based genetic algorithm on all benchmark graphs; and 3) the advantages of
EA/SM are mainly due to the introduction of the new SM operator and the new
repair-assisted restart process.
PMID- 25137738
TI - Active learning with imbalanced multiple noisy labeling.
AB - With crowdsourcing systems, it is easy to collect multiple noisy labels for the
same object for supervised learning. This dynamic annotation procedure fits the
active learning perspective and accompanies the imbalanced multiple noisy
labeling problem. This paper proposes a novel active learning framework with
multiple imperfect annotators involved in crowdsourcing systems. The framework
contains two core procedures: label integration and instance selection. In the
label integration procedure, a positive label threshold (PLAT) algorithm is
introduced to induce the class membership from the multiple noisy label set of
each instance in a training set. PLAT solves the imbalanced labeling problem by
dynamically adjusting the threshold for determining the class membership of an
example. Furthermore, three novel instance selection strategies are proposed to
adapt PLAT for improving the learning performance. These strategies are
respectively based on the uncertainty derived from the multiple labels, the
uncertainty derived from the learned model, and the combination method (CFI).
Experimental results on 12 datasets with different underlying class distributions
demonstrate that the three novel instance selection strategies significantly
improve the learning performance, and CFI has the best performance when labeling
behaviors exhibit different levels of imbalance in crowdsourcing systems. We also
apply our methods to a real-world scenario, obtaining noisy labels from Amazon
Mechanical Turk, and show that our proposed strategies achieve very high
performance.
PMID- 25137739
TI - A dual-population differential evolution with coevolution for constrained
optimization.
AB - Inspired by the fact that in modern society, team cooperation and the division of
labor play important roles in accomplishing a task, this paper proposes a dual
population differential evolution (DPDE) with coevolution for constrained
optimization problems (COPs). The COP is treated as a bi-objective optimization
problem where the first objective is the actual cost or reward function to be
optimized, while the second objective accounts for the degree of constraint
violations. At each generation during the evolution process, the whole population
is divided into two based on the solution's feasibility to treat the both
objectives separately. Each subpopulation focuses on only optimizing the
corresponding objective which leads to a clear division of work. Furthermore,
DPDE makes use of an information-sharing strategy to exchange search information
between the different subpopulations similar to the team cooperation. The
comparison of the proposed method on a number of benchmark functions with
selected state-of-the-art constraint-handling algorithms indicates that the
proposed technique performs competitively and effectively.
PMID- 25137740
TI - New techniques for mining frequent patterns in unordered trees.
AB - We consider a new tree mining problem that aims to discover restrictedly embedded
subtree patterns from a set of rooted labeled unordered trees. We study the
properties of a canonical form of unordered trees, and develop new Apriori-based
techniques to generate all candidate subtrees level by level through two
efficient rightmost expansion operations: 1) pairwise joining and 2) leg
attachment. Next, we show that restrictedly embedded subtree detection can be
achieved by calculating the restricted edit distance between a candidate subtree
and a data tree. These techniques are then integrated into an efficient
algorithm, named frequent restrictedly embedded subtree miner (FRESTM), to solve
the tree mining problem at hand. The correctness of the FRESTM algorithm is
proved and the time and space complexities of the algorithm are discussed.
Experimental results on synthetic and real-world data demonstrate the
effectiveness of the proposed approach.
PMID- 25137752
TI - Case reports have a low priority in the EJPD.
PMID- 25137753
TI - On whole person care. Dementia road map must transcend politics.
PMID- 25137754
TI - The NHS must build resilience.
PMID- 25137755
TI - Patient engagement. Press the right buttons to activate your patients.
PMID- 25137756
TI - Patient records. The dataset with no name.
PMID- 25137757
TI - Patient records: case studies. Return to the source. How health researchers are
already using pseudonymisation of data at source.
PMID- 25137758
TI - Service improvement. The exemplar hospital.
PMID- 25137759
TI - Enhanced perspective.
PMID- 25137760
TI - Frail older people improve their care. Pave the way for better elderly care.
PMID- 25137761
TI - Lessons from a school master.
PMID- 25137762
TI - Power up staff with hands-on action.
PMID- 25137763
TI - [The world of Toulouse-Lautrec--litographies of the Museum of Fine Arts].
PMID- 25137764
TI - [Dilemmas of studying rare diseases].
PMID- 25137765
TI - [The cultural history of the discovery of insulin].
PMID- 25137766
TI - [Correlations of health, happiness and wellbeing in modern society].
PMID- 25137767
TI - [Neuroethics].
PMID- 25137768
TI - The dishonest math of PPACA.
PMID- 25137769
TI - Severe ocular trauma in the emergency room.
AB - To assess the nature, severity, and mechanisms of ocular trauma in the emergency
room at an academic teaching hospital. METHODS: Individual review of patients'
records involving ocular trauma in the emergency room. Severe intraocular trauma
was defined as any injury that required intraocular surgery, any traumatic optic
neuropathy, or total destruction of the eye. RESULTS: Of 519 patients in 2010
seen in the emergency room for ocular trauma, 52 patients (10%) had severe ocular
trauma. Contusions (17) were the most common injury, followed closely by
penetrating lacerations (16) and ruptures (16). In addition, 33 of these 52
patients (63.5%) had a full-thickness open globe injury, with physical assault as
the most common etiology. CONCLUSION: The most common severe ocular traumas seen
in the emergency room were contusions, penetrating lacerations, and ruptures.
Penetrating lacerations and ruptures were the most common causes of open eye wall
injuries.
PMID- 25137770
TI - The Mississippi State Tuberculosis Sanatorium and the evolution of thoracic
surgery in Mississippi.
PMID- 25137771
TI - Call the surgeon please.
PMID- 25137773
TI - No room for error.
PMID- 25137772
TI - More thoughts on Medicaid expansion.
PMID- 25137774
TI - The Veterans Administration Hospital scandal: views of a Mississippi physician.
PMID- 25137775
TI - Securing the future of healthcare: students in your practice.
PMID- 25137776
TI - Stepping up to leadership: why oral health?
PMID- 25137777
TI - Thematic analysis of personal statements in physician assistant program
admissions.
AB - PURPOSE: The written personal statement is widely used in health professions
program admissions. The purposes of this study were to identify the common themes
manifesting in the personal statements of physician assistant (PA) program
applicants and to measure the odds of matriculation while controlling for other
admission covariates. METHODS: This study was a retrospective mixed-method
observational study of CASPA admissions data. From the aggregate pool of 14,682
CASPA applications in the 2009-2010 admissions cycle, we randomly selected a
subset of 600 unique de-identified applicants with complete application data. We
coded the major themes and subthemes for each personal statement. We then
performed maximum likelihood logistic regression analysis that compared the odds
of matriculation based on the major themes and known cognitive admission
variables. RESULTS: We identified eight major themes including altruism and the
desire to help people, challenges and hardships, experience, key accomplishments,
personal characteristics, positive perception of PA career attributes, role
models, and a religious or spiritual quest. The only major theme increasing the
odds of matriculation was role models, specifically exposure to a PA role model.
Grade-point average far exceeded all other variables influencing the odds of
matriculation. CONCLUSIONS: In this study, we found the personal statement to be
an unreliable tool for predicting successful PA program matriculation.
PMID- 25137778
TI - Generation 1.5--a different kind of millennial student.
AB - Much attention has been paid to so-called "millennial students" in recent years,
particularly regarding their relationship to technology, learning, and
communication. Less notice has been taken of another kind of millennial student
increasingly represented in our classrooms --those who were born in another
country, but received a significant amount of their schooling here. Often
referred to as Generation 1.5 because they have language characteristics in
common with first- and second-generation immigrants, these bilingual students are
a valuable resource for the physician assistant (PA) profession. However, just as
teaching native-born millennial students may require some adjustment of
instructional methods, Generation 1.5 students will require PA educators to pay
closer attention to some aspects of teaching and learning. This article will
discuss some of the particular challenges that Generation 1.5 students face and
will argue that these challenges can be met in ways that are likely to help other
nontraditional students as well.
PMID- 25137779
TI - Physician assistant specialty choice: a factor analysis.
AB - PURPOSE: The purpose of this study was to identify factors related to physician
assistant (PA) graduates' specialty choice. METHODS: A web-based cross-sectional
study of PAs graduating between 2007 and 2009 was conducted (N = 12,128). Factor
analysis was performed on 897 useable survey responses. The cohort profile
resembles that of recent AAPA census data regarding demographic and specialty
choice distribution. RESULTS: Principal component factor analysis of perception
items identified five factors that explained 52.6% of the response variance.
Factors included personal satisfaction, intellectual challenge, patient care
commitment, image of primary care, and professional satisfaction. The influence
items analysis yielded five factors, explained 45.2% of the variance, and
included practice environment, nature of patient care, lifestyle, employment
opportunities, and risk aversion. These factors parallel previous findings of
Hauer, et al. CONCLUSIONS: Identification of factors affecting specialty choice
should provide an enhanced understanding to organizations as they explore
strategies to increase recruitment and expansion of the primary care workforce.
PMID- 25137780
TI - Utilization of a self-selection process for clinical rotation assignments: a
report on student and clinical coordinator satisfaction.
AB - PURPOSE: The purpose of this study was to examine the effect of a self-selection
process for clinical rotation on student satisfaction with the program. Chatham
University provides its students with the opportunity to self-select all of their
clinical rotations from a list of pre-approved sites that have been determined to
meet accreditation standards. METHODS: A survey was administered to all senior
students enrolled in Chatham's Physician Assistant Program to assess their
perceptions of the self-selection clerkship process. In addition, a survey was
sent to all clinical coordinators nationwide to determine the techniques they
used at their programs to assign students to rotation sites. RESULTS: Of the
program's 61 students, 52 participated, yielding an 85.2% response rate. It was
determined that students are very satisfied with the process of self-selection of
the clinical rotation sites. Students reported that they take greater ownership
in their rotations, because they were assigned to the rotations they wanted.
Rotation self-selection was also reported as a desired feature of our program. Of
192 clinical coordinators that received the survey, 46 participated, and we found
that 57% allow self-selection for elective rotations, and 43% do not allow
selection of any rotations. CONCLUSIONS: Despite limitations such as loss of
sites and preceptor turnover, the self-selection process is beneficial for both
students and clinical coordinators. The process used could be easily adapted to
other physician assistant programs.
PMID- 25137782
TI - Culture, diversity, race, and the standards: assessing and addressing the hidden
curricula.
PMID- 25137781
TI - Nasal carriage of Staphylococcus aureus in physician assistant students: initial
prevalence and transmission during clinical rotations.
AB - PURPOSE: This study evaluated physician assistant (PA) students for nasal
carriage of Staphylococcus aureus (prerotations) and then again just prior to
graduation. It also attempted to correlate initial and subsequent sample results
with subject-specific survey data relating to students' general medical, social,
behavioral, and geographical situations. METHODS: Nasal swab cultures were self
collected using standardized techniques. Colonies suspicious for Staph underwent
further workup to determine if Staphylococcus aureus was present. RESULTS: Nine
(eight females, one male) of 34 subjects (26.5%) were positive for Methicillin
sensitive Staphylococcus aureus (MSSA) in the nares at baseline and all nine
subjects remained positive during the second sampling. No subjects were found to
have Methicillin-resistant Staphylococcus aureus (MRSA) at baseline and no
subjects were positive for MRSA during phase two sampling. Routine sharing of
drinks from common glassware was identified in all positive subjects, while
subjects negative for colonization reported only seldom or no participation in
that activity (P < 0.001). CONCLUSIONS: Clinical rotations did not appear to
alter carriage status. However, a strong association between nasal carriage and
participation in certain social behaviors was observed.
PMID- 25137783
TI - Targeting instructional strategies to address Gen Y learner characteristics.
PMID- 25137784
TI - Things we wish we'd known before physician assistant school: a physician
assistant student survival guide.
PMID- 25137785
TI - Fostering lifelong learning in the physician assistant student through internet
based continuing medical education.
PMID- 25137786
TI - National Nurses Week highlights the many leadership roles of nurses.
PMID- 25137788
TI - A bundle strategy including patient hand hygiene to decrease clostridium
difficile infections.
AB - Prevention strategies for Clostridium difficile infection traditionally have
addressed barrier precautions, environmental disinfection, and health care worker
hand hygiene. When applied as a bundle, this approach has been used widely as an
evidence-based strategy to prevent hospital-acquired C. difficile infection.
Expanding the bundle to include patient hand hygiene is a nurse-driven approach
to prevent C. difficile transmission.
PMID- 25137787
TI - Seriously now...hospital food is no joke.
PMID- 25137789
TI - Empowering the development of a nurse-driven protocol.
AB - Results from a research project examining nurses' knowledge of diabetes empowered
direct-care nurses to develop a hypoglycemia protocol, increasing accountability
for the care provided and helping move from tradition-based to evidence-based
practice.
PMID- 25137790
TI - Stemming the obesity epidemic: are nurses credible coaches?
AB - Obesity has become a health crisis in the United States, leading to serious
physical, social, and psychological outcomes. Nurses are obese in the same
proportion as the general population, which may discredit them as role models of
and educators for healthful living.
PMID- 25137791
TI - Decision-making models used by medical-surgical nurses to activate rapid response
teams.
AB - Medical-surgical nurses were queried about the decision-making process used to
request assistance from the rapid response team (RRT). Results indicated the type
of process is correlated to the frequency of RRT calls made.
PMID- 25137792
TI - Taste dysfunction and eating behaviors in survivors of head and neck cancer
treatment.
AB - Radiation, chemotherapy, and surgery result in eating problems for patients with
head and neck cancer. Eating is essential to physical and social functioning.
Strategies for head and neck cancer survivors to cope with eating and taste
impairments are reported in this study.
PMID- 25137793
TI - Postoperative management of patients with obstructive sleep apnea: implications
for the medical-surgical nurse.
AB - Obstructive sleep apnea (OSA) affects up to 7% of Americans, and those undergoing
surgery are at risk for complications. Medical-surgical nurses should be
knowledgeable regarding this common disorder and understand how to screen
effectively and monitor patients with OSA.
PMID- 25137794
TI - Nursing knowledge of physiological and psychological outcomes related to patient
sleep deprivation in the acute care setting.
AB - In this study, nurses' knowledge regarding sleep quality outcomes in the acutely
ill patient population was assessed. Also evaluated was the possible impact of
nurses' knowledge of the effects of quality sleep on their choice of activities
to promote patient rest.
PMID- 25137796
TI - Use of theoretical frameworks in research.
PMID- 25137795
TI - Making ABGs simple.
PMID- 25137798
TI - Monkey in the middle!
PMID- 25137797
TI - Informed consent: whose duty to inform?
PMID- 25137799
TI - Harm reduction: compassionate care of persons with addictions.
PMID- 25137800
TI - Conscientious objection in nursing: definition and criteria for acceptance.
PMID- 25137802
TI - A compromise.
PMID- 25137801
TI - Clement Victor Vignes, A.M., D.D.S.,D.SC., F.A.C.D.
PMID- 25137803
TI - Governmental affairs and national initiative update.
PMID- 25137804
TI - Do you remember?
PMID- 25137805
TI - Computer placement in the treatment rooms.
PMID- 25137806
TI - The Family Bank Trust.
PMID- 25137807
TI - Clinical analytics for data-driven models of care.
PMID- 25137808
TI - A population-based care transition model for chronically ill elders.
AB - Elders with chronic illness are hospitalized more often than those without major
chronic disease, and nearly one-fifth of hospitalizations result in re-admission
within 30 days of discharge from the hospital. Care transition management
programs address chronic disease complexity to reduce unnecessary
hospitalization, improve quality of care, and reduce medical expense. This report
describes how informatics influenced the transformation of a regional managed
care organization from one focused on specific chronic disease prevalence to one
targeting population-specific chronic conditions based on complexity. The key
implication of these results is that population-based informatics can amplify the
impact of programs designed to improve quality and prevent avoidable admissions
and, at the same time, speed the rate of translation of evidence-based
interventions to entire populations. This approach demonstrated an effective,
efficient way to translate evidence-based research to the Medicare population,
smoothing the transition back into the community, and preventing avoidable
hospital admissions.
PMID- 25137809
TI - Group visits for chronic illness management: implementation challenges and
recommendations.
AB - The group visit approach to improve chronic illness self-management appears
promising in terms of selected outcomes, but little information is available
about best ways to organize and implement group visits. This literature review of
84 articles identified group visit implementation challenges, including lack of a
group visit billing code, inadequate administrative support and resources,
difficult participant recruitment and retention, and logistical issues such as
space and scheduling. Recommendations for future implementation initiatives were
also abstracted from the literature. Patients and providers can benefit from well
planned and well-conducted group visits. These benefits include greater patient
and provider satisfaction, reduced overall utilization, improved clinical
outcomes, and greater provider efficiency and productivity.
PMID- 25137810
TI - A hospital system approach at decreasing falls with injuries and cost.
AB - Falls and fall-related injuries continue to challenge every health care
organization. Falls are a nurse-sensitive quality outcome. Patient falls are a
leading cause of injuries in hospitals, considered to be among the most expensive
adverse event, and continue to be a patient safety concern. Researchers analyzed
the impact of a standardized fall prevention program across 50 acute care
hospitals in 11 states. The implementation of a standardized multifactorial
program for adult patients appears to have reduced falls with injuries by 58.3%
over a 2-year period, allowing for a potential cost avoidance reduction of
$776,064 in 2013 dollars.
PMID- 25137811
TI - Nurse staffing and the relationship to job satisfaction and retention.
AB - The purpose of this quantitative, correlational research study was to examine the
relationships between nurse staffing, job satisfaction, and nurse retention in an
acute care hospital environment. Results indicated a moderately strong, inverse
relationship between job satisfaction and nurse retention. A weak positive
relationship between job satisfaction and nurse staffing was identified. Nurses
reported experiencing job dissatisfaction in the past 6 months specifically
related to the number of patients assigned. Analysis suggested nurses are staying
with their current employer because of the current economic environment.
Improving nurse staffing will be necessary when the economy improves to prevent
the departure of discontented nurses from acute care facilities.
PMID- 25137812
TI - Hospital performance in China: do location and hospital level matter?
AB - In this study, the operational and financial differences of hospitals were
assessed by geographical area and by various levels of government ownership.
Hospital geographic location (east, middle, and west) had a significant impact on
hospital financial performance, but no significant influence on operational
performance. Hospital government ownership level (province, city, and county) had
a significant influence on both operational and financial performance. China's
current public policy of not fully subsidizing its public hospital systems and
limiting their ability to set prices for certain health care services may have
negative and unintended consequences in its ability to provide needed health care
services to its population. The government should revisit its policies to
eliminate the differences regarding hospital performance related to location and
government ownership levels.
PMID- 25137813
TI - Building staffing science: two milestones.
AB - Health care and nurse staffing present interesting challenges for nursing and
health care leaders. The recently released Evidence and Excellence in Staffing
(2nd edition) creates a framework for research and organizational improvement
that leads to the development and sharing of best practices. A new model for
staffing excellence has emerged with five core concepts. This new position paper
calls for generating and disseminating 25-30 new best practices in nurse staffing
across the care continuum over the next 3 years.
PMID- 25137815
TI - Caring for myself so that I can care for others.
PMID- 25137814
TI - Planes, trains, and other interruptions: such is life!
AB - Nurse leaders can spend a significant part of their careers traveling. Self-care
and personal mindfulness need not suffer when we are away from home and our
normal routine. Personal health plans can be adapted in practical ways to travel
with you. So pack your bags with whatever feeds your self-nurturing needs, grab
some kale chips and comfortable shoes, and let's get going!
PMID- 25137816
TI - Waiting for your coronation: a career-limiting trap.
AB - Women are often reluctant to apply for promotions even when they are well
deserved, simply believing good job performance will naturally lead to rewards.
This phenomenon of advancement reticence has led to such labels as "tiara
syndrome," "girl disease", and "imposter syndrome". Women often undervalue their
skills and are less effective at self-promotion than their male counterparts. A
number of strategies can help battle these "syndromes" and ease the stress of
"taking off the tiara".
PMID- 25137817
TI - Using the lens of history to understand nursing practice and policy: an interview
with Julie Fairman.
PMID- 25137818
TI - Paying it forward: Nursing Economic$ award winners reflect.
PMID- 25137819
TI - I Love Lucy, George C. and Twitty too.
PMID- 25137820
TI - Alan Kirk Wilson, MD. Focused physician has presidential ambitions for AMS member
participation.
PMID- 25137821
TI - 2014 hypertension and cholesterol guidelines.
PMID- 25137822
TI - 2014 Awards Luncheon recognition for outstanding service.
PMID- 25137823
TI - Highlights from House of Delegates meeting & word from the AMA.
PMID- 25137824
TI - Physician communication in a social media climate. To share or not to share-
thoughts on each side.
PMID- 25137825
TI - Arkansas payment improvement initiative. Episodes of care update.
PMID- 25137826
TI - Historical insights in the progression and development of gingivectomy.
AB - During the last three centuries since the identification of periodontal disease,
various non-surgical and surgical forms of periodontal therapy have been
described and documented in the dental literature. The main objective of
periodontal treatment has been initially the removal of "diseased gingiva,"
either through the implementation of various surgical techniques, or through the
application of caustic drugs or pressing patches. Although the differences in the
suggested techniques created significant controversies between some of the
greatest clinicians and researchers in dentistry, their main goals remained the
rehabilitation of the oral cavity and the therapeutic management of the problems
sustained from periodontal disease.
PMID- 25137827
TI - A short history of the Royal Odonto Chirurgical Society of Scotland.
AB - In the mid-19th Century, the practice of dentistry in Britain was unregulated and
chaotic. Organised training was non-existent, and the public was unable to be
assured of satisfactory, ethical treatment. A group of Scottish practitioners,
led by John Smith, an Edinburgh surgeon, established the Odonto Chirurgical
Society of Scotland in 1867 as an ethical dental society promoting education and
regulation of the emerging profession. The Society has prospered over the years.
It was granted the title "Royal" on the occasion of its centenary in 1967, and
approaches its 150th year with confidence.
PMID- 25137828
TI - Historical perspectives on the roots of the apical negative pressure irrigation
technique in endodontics.
AB - The removal of the infectious process caused by an abscess in the periapical
tissues was a challenge to dentists in the early part of the 20th century. While
they recognized the need to debride the periapical tissues, the process was slow,
tedious, and often fraught with failure that resulted in tooth extraction.
However, with some creative ingenuity, an irrigation-suction apparatus was
developed in the 1930s that enabled rapid and thorough debridement. This
appliance went through multiple developmental permutations and was successful in
achieving the desired goal. Interestingly, while the purpose of this device was a
controlled periapical debridement through the root canal, and not necessarily a
focus on a cleaning of the intricacies of the root canal system, the basic
concept purported was similar to contemporary approaches used in root canal
debridement today.
PMID- 25137829
TI - Dental Postcards LV. Dr. Ernest A Carpenter: an early advocate of preventive
dentistry.
PMID- 25137830
TI - Dental trade cards XL. A toothbush in hand.
PMID- 25137831
TI - What stress is doing to your brain.
PMID- 25137833
TI - Diabetic cooking.
PMID- 25137832
TI - Family awareness. Monitoring diabetes risk.
PMID- 25137834
TI - Blood glucose self-monitoring. Part 2: monitoring technique.
AB - To measure the concentration of glucose in your blood, you put a strip in the
meter, poke a hole in your finger to get a sample of blood, touch the tip of the
test strip to the drop of blood, and wait for the result. It sounds pretty
straightforward. But, of course, the devil is in the details.
PMID- 25137835
TI - Talking about diabetes. Six tips for improved communication.
PMID- 25137837
TI - [An expert in integrative medical cardiology].
PMID- 25137836
TI - What your doctor is reading.ore evidence for value of bariatric surgery.
PMID- 25137838
TI - [Several problems we should pay attention to in scientific research on
integrative medicine].
PMID- 25137839
TI - [Therapeutic effect of Astragalus and Angelica mixture on the renal function and
TCM syndrome factors in treating stage 3 and 4 chronic kidney disease patients].
AB - OBJECTIVE: To compare the therapeutic effect of Astragalus and Angelica Mixture
(AAM) on treating CKD patients according to different CKD primary diseases,
staging and TCM syndromes. METHODS: A multicentre, open-label, and self control
clinical design was used, and thirty-two patients in line with inclusive criteria
were recruited. Based on maintaining their previous basic CKD treatment, patients
additionally took AAM (Astragalus and Angelica each 30 g), once a day, three
months consisted of one therapeutic course. Serum creatinine (SCr), estimated
glomerular filtration rate (eG- FR), 24 h urinary total protein (UTP), plasma
albumin (ALB), hemoglobin (Hb), and changes of TCM syndrome factor integrals were
compared before treatment, at the end of month 1, 2, and 3. The differences in
the aforesaid indices were compared between CKD patients with different CKD
primary diseases (chronic glomerulonephritis, chronic renal tubulointerstitial
disease, hypertensive renal damage), different CKD stages (CKD 3 and CKD 4), and
patients of qi-blood deficiency syndrome (QBDS) and non-QBDS. RESULTS: AAM could
improve 78.12% (25/32) patients' renal function. Compared with before treatment,
SCr decreased (12.08% +/- 10.11%), eGFR increased (21.14% +/- 18.55%), and ALB
increased (2.76% +/- 1.97%) at the end of 3-month treatment (all P < 0.05). As
for TCM syndrome factor integrals, compared with before treatment, the integrals
for qi deficiency syndrome, blood deficiency syndrome, and yin deficiency
syndrome decreased, while the integrals for dampness heat syndrome and turbid
toxin syndrome increased (all P < 0.05). There was no obvious difference in all
indices except the integral for hypertensive renal damage patients of yin
deficiency syndrome (P > 0.05). The SCr decreasing percent was 19.82% +/- 8.30%
for patients of non-QBDS and 5.24% +/- 10.75% for patients of QBDS. The latter
was higher with statistical difference (P < 0.05). As for TCM syndrome factor
integrals, the integral differences of qi deficiency and blood deficiency were
obviously higher in patients of QBDS, when compared with patients of non-QBDS (P
< 0.05). CONCLUSION: AAM could improve the renal function of CKD patients,
elevate their ALB levels, and ameliorate associated qi deficiency syndrome, blood
deficiency syndrome, and yin deficiency syndrome, especially for CKD patients of
QBDS.
PMID- 25137840
TI - [Effect of Chinese herbal therapy on T-lymphocytes of IgA nephropathy patients: a
clinical observation].
AB - OBJECTIVE: To observe the effect of Chinese herbal therapy on T-lymphocyte
subsets in patients with IgA nephropathy (IgAN). METHODS: Totally 36 inpatients
and outpatients at Department of Nephropathy, Xiyuan Hospital, China Academy of
Chinese Medical Sciences, from June 2011 to June 2013 were recruited in the
treatment group, while 20 volunteers were recruited as the healthy control group.
Patients in the IgAN group only took Chinese herbal decoctions by syndrome typing
for 3 months (except those accompanied with hypertension additionally took
antihypertensive agents such as angiotensin-converting enzyme inhibitor and/or
dihydropyridines calcium antagonist). No intervention was performed in the
healthy control group. The values of Th1, Th2, and CD4+ CD25+ Treg, and red blood
cell number in urine were detected using flow cytometry before and after
treatment. 24 h urine protein was detected using inmmunoturbidimetry. RESULTS:
Compared with the healthy control group, the CD4+ CD25+ Treg level obviously
decreased in the IgAN group, showing statistical difference (P < 0.01). In the
IgAN group, Th1, 24 h urine protein, and urine red blood cell counts were
obviously lower after treatment, showing statistical difference when compared
with before treatment (all P < 0.05). CONCLUSION: Chinese herbal therapy could
reduce urine erythrocyte number and 24 h urine protein of IgAN patients, and down
regulating Th1 expression might be its mechanism.
PMID- 25137841
TI - [Clinical analysis of syndrome-relative biological indices in acute lacuna
encephalon infarction patients of upper hyperactivity of Gan Yang syndrome].
AB - OBJECTIVE: To analyze and summarize changes of syndrome-related biological
indices in acute lacuna encephalon infarction patients of upper hyperactivity of
Gan yang syndrome (UHGYS), thus providing objective evidence for syndrome typing
and disease identification. METHODS: Recruited were 50 patients at Department of
Encephalopathy, Xiyuan Hospital, China Academy of Chinese Medical Sciences, who
were in line with diagnostic criteria of UHGYS as the experimental group in this
study. Another 40 healthy volunteers were recruited as the control group from May
2010 to July 2012. Blood routines (including WBC, RBC, Hb, NEUT%, and LY%),
hepatic and renal functions tests (including ALT, AST, TBIL, TP, ALB, Cr, and
BUN) were performed by automatic whole blood analyzer and colorimetric technique.
The levels of fasting blood glucose, HbAlc, blood lipids (including TC, TG, HDL
C, LDL-C, and VLDL-C), and coagulation functions (including AT-III, PT, PTA, INR,
TT, APTT, and FBG, reaction time), renin, angiotensin II, hs-CRP, and Hcy were
also measured. The thyroid functions (including FT3, FT4, T3, T4, and TSH) were
detected by electrochemiluminescence immunoassay. The levels of tumor necrosis
factor alpha (TNF-alpha), IL-6 and IL-1 in serum were measured by ELISA and
radioimmunoassay respectively. RESULTS: Compared with the control group, RBC,
LY%, ALT, TP, ALB, HDL-C, AT-III activities, contents of PTA and FT4 obviously
decreased, TBIL, BUN, Glu, HbAlc, TSH, hs-CRP, renin, Ang II, TNF-alpha, IL-1 and
IL-6 significantly increased in the experimental group (P < 0.05, P < 0.01).
CONCLUSION: The pathological process of acute lacuna encephalon infarction
patients of UHGYS was closely correlated with thyroid functions, the renin
angiotensin-aldosterone system, the extrinsic and intrinsic coagulation systems,
as well as inflammation reaction.
PMID- 25137842
TI - [Effect of acupuncture-anesthetic composite anesthesia on the incidence of POCD
and TNF-alpha, IL-1beta, IL-6 in elderly patients].
AB - OBJECTIVE: To explore the effect of acupuncture-anesthetic composite anesthesia
(AACA) on the incidence of postoperative cognitive dysfunction (POCD) and changes
of TNF-alpha, IL-1beta, and IL-6 in elderly patients. METHODS: Totally 83
patients undergoing surgical resection of gastrointestinal tumor were randomly
assigned to the simple anesthesia group (A group, 41 cases) and the AACA group (B
group, 42 cases). Patients in Group A received endotracheal general anesthesia.
Those in Group B were induced by acupuncture anesthesia for 30 min by needling at
Baihui (DU20), Neiguan (PC6), Zusanli (ST36). The electro-acupuncture (EA)
apparatus was connected after arrival of qi, with the wave pattern of density
2/100 Hz. The stimulus intensity was set by patients' tolerance, with the peak
current of 5 mA. Then the endotracheal general anesthesia was performed and the
EA lasted till the end of the surgery. The cognitive function of all patients was
assessed before operation and at day 3 after operation using mini-mental state
examination (MMSE). POCD was confirmed if with one or more decreased stand- ard.
The peripheral venous blood was collected before anesthesia induction (TO),
immediately at the end of surgery (T1), 24 h after operation (T2), and 48 h after
operation (T3), and serum concentrations of IL-1beta, IL-6, and TNF-alpha were
correspondingly measured using ELISA. RESULTS: The postoperative anesthesia
awakening time was shorter in Group B than in Group A [(20.37 +/- 6.09) min vs
(29.24 +/- 7.48) min, P < 0.05]. The remifentanil dose used during the operation
was less in Group B than in Group A (P < 0.05). The incidence of POCD at day 3
was lower in Group B than in Group A [10/41 (23.8%) vs 15/42 (36.5%), P < 0.05].
The concentrations of IL-1beta, IL-6, and TNF-alpha at T1-T3 were higher than
those at TO in the two groups (P < 0.05). The increment of TNF-alpha and IL-1beta
was less in Group B than in Group A (P < 0.05). CONCLUSION AACA could reduce the
incidence of POCD and inhibit postoperative release of TNF-alpha, IL-1beta, and
IL-6 in elderly patients undergoing colorectal cancer resection.
PMID- 25137843
TI - [Jiawei shentong zhuyu decoction prevented the occurrence of failed back surgery
syndrome and its effect on serum TNF-alpha a clinical study].
AB - OBJECTIVE: To explore the clinical roles of Jiawei Shentong Zhuyu Decoction
(JSZD) in preventing the occurrence of failed back surgery syndrome (FBSS), and
to observe its effect on serum tumor necrosis factor-alpha (TNF-alpha). METHODS:
Totally 100 patients prepared for surgical operation due to lumbar intervertebral
disc herniation were randomly assigned to the treatment group and the control
group according to random number table, 50 cases in each group. Patients in the
treatment group additionally took JSZD, one dose per day, taken in two portions,
once in the morning and once in the evening. Those in the control group took
Celecoxib Capsule (200 mg each time, once per day) and Mecobalamin Tablet (0.5 mg
each time, 3 times per day). They only took Mecobalamin Tablet from the 11th day.
All patients were treated for 30 days. Japanese Orthopaedic Association (JOA)
score was performed before treatment, at week 1, after treatment, at 6 months of
followed-ups, and at 12 months of followed-ups. And the levels of TNF-alpha in
the peripheral blood were observed before treatment and at one month after
treatment. RESULTS: Totally 93 patients completed the followed-up study. The JOA
scores were improved after treatment, at 6 and 12 months of followed-ups (P <
0.05, P < 0.01). The JOA score at 6 months of followed-ups was superior in the
treatment group to that of the control group (P < 0.05). Five patients
(accounting for 10.6%) suffered from FBSS in the treatment group, while 9
(accounting for 19.6%) suffered from FBSS in the control group. The treatment
group was superior to the control group (P < 0.05). The TNFalpha level was
improved after treatment in the two groups. Of them, the improvement of TNF-alpha
in the treatment group was better than that of the control group (P < 0.05).
CONCLUSION: The application of JSZD was effective for preventing the occurrence
of FBSS, and improved the serum TNF-alpha level.
PMID- 25137844
TI - [Effect of application of acupuncture-anesthetic composite anesthesia on
hysteroscopic surgery: a clinical study].
AB - OBJECTIVE: To observe the analgesic effect and safety of acupuncture-anesthetic
composite anesthesia (AACA) in hysteroscopic surgery. METHODS: Totally 93
patients undergoing hysteroscopic surgery were randomly assigned to the
intravenous anesthesia group (A group, 30 cases), the AACA group (B group, 32
cases), and the acupuncture combined with intravenous anesthesia group (C group,
31 cases). Patients in Group A were anesthetized by sufentanil combined propofol.
Those in Group B were anesthetized by sufentanil combined acupuncture. Those in
Group C were anesthetized by sufentanil, propofol combined acupuncture. Yinlian
and Ququan (LR8) were needled for patients in Group B and C. The peri-operative
mean arterial pressure (MAP), heart rate (HR), and oxygen saturation (SpO2), the
surgical time, the recovery time, the sufentanil and propofol dosages, adverse
anesthesia reactions were observed. Meanwhile, the OAA/S score, Ramsay sedation
score, and Visual Analogue Score (VAS) were also measured. RESULTS: Compared with
Group A and C, patients in Group B were awake, with obvious increased OAA/S score
(P < 0.01). Ramsay sedation score was significantly lower (P < 0.01).The MAP and
HR were elevated (P < 0.05). The patient case of SpO2 less than 85% during the
operation decreased (P < 0.05). The incidence of postoperative dizziness was
reduced (P < 0.05). Compared with Group A, the propofol consumption decreased in
Group C (P < 0.05). There was no statistical difference in the operation time,
the sufentanil dosage, VAS score, the incidence of postoperative nause- a and
vomiting among the three groups (P > 0.05). CONCLUSIONS: The patients were awake
in AACA. The intraoperative sedation was better than that obtained by intravenous
anesthesia. But the analgesic effect was similar to that obtained by intravenous
anesthesia.
PMID- 25137845
TI - [Treatment of chronic heart failure of Xin-Shen yang deficiency, interior
retention of water-fluid syndrome by external application of Zhuangshenling
recipe combined with western medicine: a clinical study].
AB - OBJECTIVE: To observe the effect of external application of Zhuangshenling Recipe
(ZR) combined with Western medicine (WM) on the heart function of chronic heart
failure (CHF) patients of Xin-Shen yang deficiency, interior retention of water
fluid syndrome (XSYDIRWFS). METHODS: Totally 140 CHF patients of XSYDIRWFS were
randomly assigned to two groups, the treatment group and the control group, 70 in
each group. All patients received WM therapy. Those in the treatment group were
applied with ZR at Xinshu (BL15) and Shenshu (BL23), while those in the control
group were applied with placebos at Xinshu (BL15) and Shenshu (BL23). The
therapeutic course for all was 12 weeks. The integrals of TCM syndrome, grading
of cardiac function, brain natriuretic polypeptide (BNP), and 6 min walking
distance were observed before and after treatment. RESULTS: After twelve weeks of
treatment, the effective rate of improved grading of cardiac function, the total
effective rate of TCM syndrome efficacy, and the BNP level were obviously better
in the treatment group (P < 0.05). There was no statistical difference in 6 min
walking distance between the two groups (P > 0.05). CONCLUSION: External
application of ZR combined with WM could improve the heart function of CHF
patients of XSYDIRWFS.
PMID- 25137846
TI - [Effect of Chinese drugs for Pi strengthening Shen benefiting on the immunity
function of HIV patients' specific T cells].
AB - OBJECTIVE: To explore the effect of Chinese drugs for Pi strengthening Shen
benefiting (CDPSSB) on the immunity function of HIV/AIDS patients' specific T
cells. METHODS: Totally 20 patients were randomly recruited from the treated
group [treated by CDPSSB combined highly active anti-retroviral therapy (HAART)]
and 23 patients were randomly recruited from the control group (treated by HAART
alone). All patients were follow-up infected persons form You'an Hospital between
from June 2010 to June 2012. CD4+ T absolute counts and HIV viral load were
detected. Meanwhile, HIV whole gene overlapping peptides were used as stimulating
antigen. The response intensity of HIV specific T cells was detected in the two
groups. RESULTS: There was no statistical difference in CD4 T absolute counts or
HIV viral load between the two groups (P > 0.05). The response intensity of HIV
specific T cells was significantly enhanced in the treated group, when compared
with the control group (P < 0.05). Along with elongation of treatment time (6,
12, 18, and 24 months) in the treated group, the response intensity of HIV
specific T cells showed enhancing tendency, but there was no statistical
difference among these time points (P > 0.05). CONCLUSION: CDPSSB could enhance
improve the immunity function of HIV specific T cells, which might be one of its
mechanisms.
PMID- 25137847
TI - [Analysis of tongue figure features in 990 cases of sexually transmitted and
intravenous drug use spread HIV infected population in Xinjiang].
AB - OBJECTIVE: To investigate the tongue manifestation features of sexually
transmitted and intravenous drug use spread HIV infected population in Xinjiang.
METHODS: Recruited were 990 HIV infected subjects in Xinjiang from May 2011 to
March 2012, who were assigned to the intravenous drug use spread HIV infected
(498 cases) and the sexually transmitted (492 cases). By using tongue figure
shoot combined with analyses of experts, tongue manifestations were analyzed and
compared between the sexually transmitted and the intravenous drug use spread
from four aspects, i.e., the tongue color, the tongue shape, the fur color, and
the fur property. RESULTS: Compared with the sexually transmitted population, red
tongue, fissured tongue, yellow fur, thick fur, eroded fur, deficiency of fur
fluid were more often seen, showing statistical difference (P < 0.05). Compared
with the intravenous drug use spread population, pale tongue, white fur, and thin
fur were more often seen, showing statistical difference (P < 0.05). CONCLUSIONS:
The tongue manifestations of the intravenous drug use spread HIV population
reflected inner exuberance of evil toxin and heat impairing qi and yin. Compared
with the intravenous drug use spread population, the attack of HIV infection was
more hiding in the sexually transmitted population, with milder internal injury.
Their Wei-qi was not damaged and no obvious change occurred in the tongue figure.
PMID- 25137848
TI - [Effect of compound qingqin liquid on the expression levels of ang II and COX-2
mRNA transcription and protein expression in the renal tissue of uric acid
nephropathy rats: an experimental study].
AB - OBJECTIVE: To investigate the effect of Compound Qingqin Liquid (CQL) on the
expression level of angiotensin II (Ang II) and COX-2 mRNA transcription and
protein expression in the renal tissue of rats with uric acid nephropathy.
METHODS: SD rats were randomly divided into the blank control group, the model
group, the positive drug group, the high, moderate, and low dose CQL group
according to number randomization principle. The model was established by
gastrogavage of adenine, accompanied with yeast feeding. Distilled water was
given by gastrogavage to rats in the blank control group and the model group.
Allopurinol at the daily dose of 9.33 mg/kg was given by gastrogavage to rats of
the positive control group. CQL at the daily dose of 3.77 g/kg, 1.89 g/kg, and
0.09 g/kg was respectively given by gastrogavage to rats in the high, moderate,
and low dose CQL groups. All treatment lasted for 6 weeks. Rats were randomly
divided at week 4 (3 in the blank control group, and 6 in the rest groups), and
the rest rats were killed at week 6. The renal tissue was extracted. The
expression level of Ang II and COX-2 mRNA transcription were detected by RT-PCR.
The expression level of Ang II was detected by ELISA. The expression level of COX
2 protein was detected by Western blot and immunohistochemical assay. RESULTS:
Compared with the blank control group, except the mRNA expression of Ang II at
week 4, the mRNA and protein expression of Ang II and COX-2 obviously increased
at week 4 and 6 in the model group (P < 0.01, P < 0.05). The COX-2 protein
expression at week 4 was obviously lower in the high and moderate dose CQL groups
than in the model group and the low dose CQL group (P < 0.05); the average
integral of optical density value was obviously lower in the positive control
group than in the model group. Except the mRNA expression of Ang II in the high
dose CQL group at week 6, the mRNA and protein expression of Ang II obviously
decreased in the positive control group and each dose CQL group (P < 0.01, P <
0.05). Of them, the effects were better in the high and moderate dose CQL groups
than in the positive control group and the low dose CQL group (P < 0.05, P <
0.01). Besides, the mRNA expression of COX-2, the average integral of optical
density value were obviously lower in the positive control group and each dose
CQL group than in the model group (P < 0.05). The protein expression of COX-2 was
obviously lower in the high and moderate dose CQL groups than in the model group
(P < 0.05). Of them, the mRNA expression of COX-2 was better in the moderate dose
CQL group than in the positive control group (P < 0.05); the protein expression
of COX-2 was better in the high dose CQL group than in the low dose CQL group (P
< 0.05). CONCLUSION: CQL was capable of lowering the expression level of Ang II,
COX-2 mRNA transcription and protein expression, thus suppressing the
inflammatory pathological injury of the renal tissue.
PMID- 25137849
TI - [Renal protection of Tangke Decoction on rats with diabetes and its effect on the
expression of TGF-beta1/Smad4].
AB - OBJECTIVE: To observe the effect of Tangke Decoction (TD) on the expression of
TGF-beta1/Smad4 of rats with early diabetes and to explore the effect and
mechanism of TD against the renal injury induced by diabetes. METHODS: SD rats
were randomly divided into the normal control group (n = 12), the model group (n
= 10), the Chinese herbs prevented group (n =10), the Chinese herbs treated group
(n = 10), and the Western medicine control group (n = 10). TD (18 mg/kg) was
given by gastrogavage to rats in the Chinese herbs prevented group immediately
after successful modeling for 12 weeks, once daily. At the 4th week of successful
modeling, rats in the rest 4 groups were administered by gastrogavage. Equal
volume of normal saline was given to rats in the model group and the normal
control group. Benazepril suspension (1 mg/kg) was administered by gastrogavage
to rats in the Western medicine control group for 8 weeks, once daily. TD (18
mg/kg) was given by gastrogavage to rats in the Chinese herbs treated group for 8
weeks, once daily. The body weight, kidney weight, index of kidney weight,
fasting blood sugar, 24 h urinary albumin excretion rate were examined after
experiment. The pathological changes of the renal tissue were observed by HE
staining, Masson staining, and electron microscope. The expression of renal
transforming growth factor-beta1, (TGF-beta1) and Smad4 were detected using
immunohistochemical assay. RESULTS: Compared with the normal control group, the
body weight of rats decreased significantly; the kidney weight, index of kidney
weight, blood sugar, 24 h urinary protein excretion, the urinary albumin
excretion rate,TGF-beta1 and Smad4 expression increased significantly in the
model group (all P < 0.01). Compared with the model group, the aforesaid indices
were improved in each treatment group with statistical difference (P < 0.05, P <
0.01). Compared with the Western medicine control group, the kidney weight, index
of kidney weight, blood sugar, 24 h urinary protein excretion, and the urinary
albumin excretion rate were obviously improved in the Chinese herbs prevented
group (P < 0.01). The renal pathological changes were most obvious in the model
group significantly, but they were improved in all treatment groups. CONCLUSION:
TD could obviously improve the symptoms of diabetes and down-regulate the
expression of renal TGF-beta1 and Smad4 of early diabetic nephropathy rats, which
suggested that TD had certain preventive effect on early diabetic nephropathy.
PMID- 25137850
TI - [Ginkgo biloba extract 50 inhibited beta-amyloid-induced oxidative stress in
rats' hippocampal neurons: an experimental study].
AB - OBJECTIVE To study the in vitro effect and mechanism of Ginkgo biloba Extract 50
(GBE50) for inhibiting beta-amyloid (Abeta)-induced oxidative stress in rats'
hippocampal neurons. METHODS: The primary hippocampal neurons were cultured in
vitro and divided into 4 groups, i. e. the normal control group (Ctrl), the Abeta
group, the propanediol control group (PDO), and the six GBE50 concentrations
groups (5, 10, 25, 50, 100, and 200 microg/mL). Excepted the Ctrl group, neurons
were induced to oxidative stress by 20 gmolLAbeta25-35. The MTT and fluorescent
probes labeling were used to observe the effect of GBE50 with different
concentrations on the cell viability and the generation of intracellular reactive
oxygen species (ROS) in neurons. Furthermore, Western blot was used to detect the
cytoplasmic/total cytochrome C (Cyto C) ratio and total intracytoplasmal Cyto C,
and the effect of the expression of oxidative stress-related protein Cyto C and
activated Caspase-3 in three GBE50 concentrations groups (25, 50, and 100
microg/mL). RESULTS: Compared with the Ctrl group, the cell vitality was
obviously lowered and intracellular ROS generation significantly increased after
induction of 20 micromol/L Abeta25-35 (both P < 0.05). Compared with the Abeta
group, the cell vitality was evidently improved after treated with different
GBE50 doses. Except for 10 microg/mL, the cell vitality could be obviously
elevated along with increased drug concentrations (P < 0.05). Meanwhile, the
intracellular ROS generation decreased significantly in each GBE50 dose groups (P
< 0.05). Abeta could increase the cytoplasmic/total Cyto C ratio and enhance the
activated Caspase-3 expression significantly (P < 0.05). Compared with the Abeta
group, among the three concentrations of GBE50, the Cyto C ratio was obviously
lowered in the 100 microg/mL GBE50 group (P < 0.05), and the expression of
activated Caspase-3 significantly decreased in 50 microg/mL and 100 microg/mL
GBE50 groups (P < 0.05). CONCLUSIONS : 20 micromol/L Abeta25-35 could induce the
generation of intracellular ROS in hippocampal neurons. GBE50 could inhibit Abeta
induced intracellular oxidative stress of neurons through lowering the
cytoplasmic/total Cyto C ratio and inhibiting the activation of apoptosis protein
Caspase-3 expression.
PMID- 25137851
TI - [Effect of advanced glycation end products on the function and angiogenesis of
adipose tissue-derived stem cells and the protective effect of danhong injection:
an experimental study].
AB - OBJECTIVE To investigate the effect of Nepsilon-(carboxymethyl) lysine albumin
(CMLs), a primary advanced glycation end products (AGEPs) isoform in diabetic
body, on the function and angiogenesis of adipose tissue-derived stem cells
(ADSCs) and the protective effect of Danhong Injection (DH). METHODS Human ADSCs
were cultured and separated from human subcutaneous fatty tissue using enzymatic
digestion and centrifugation. The morphology was observed using optical
microscope and differentiation capacities assessed. Cells were exposed to 5
different interventions respectively for 24 h, i.e., PBS, 60 1 microg/mL BSA, 60
microg/mL CML-BSA, 100 microL/mL DH, and 60 micro./mL CML-BSA +100 microL/mL DH.
Their effect on the proliferation, migration, apoptosis, and secretion were
observed using WST-1 assay, Transwell assay, Annexin V-FITC/PI flow meter test
reagent kit, human VEGF reagent kit, ELISA reagent kit, respectively. The effect
on ADSCs angiogenesis was observed by in vitro angiogenesis test. RESULTS:
Compared with the BSA group, the capacities of proliferation and migration could
be significantly inhibited by CML-BSA, the apoptosis promoted, the secretion of
VEGF reduced, and the angiogenesis of ADSCs weakened (P < 0.05). Compared with
the blank control group, 100 microL/mL DH could significantly promote the
proliferation and migration capacities of ADSCs, inhibit apoptosis of ADSCs,
increase the secretion of VEGF, and improve the angiogenesis of ADSCs (P < 0.05).
Compared with the CML-BSA group, the inhibition of CML-BSA on the proliferation
and migration capacities of ADSCs could be significantly reversed, the promotion
of CML-BSA on the apoptosis of ADSCs improved, the secretion of VEGF increased,
and the angiogenesis of ADSCs elevated (P < 0.05). CONCLUSION: clusion CMLs could
significantly inhibit the proliferation and migration capacities of ADSCs,
promote their apoptosis, and inhibit their angiogeneses, which could be improved
by DH.
PMID- 25137852
TI - [Effect of zhenqing recipe on non-alcoholic fatty liver in type 2 diabetes rats
and the expression of SIK1].
AB - OBJECTIVE: To observe the effect of Zhenqing Recipe (ZQR) on non-alcoholic fatty
liver (NAFL), and the expression of hepatic salt-inducible kinase 1 (SIK1) and
sterol-regulatory element binding protein-ic (SREBP-lc) in type 2 diabetes rats.
METHODS: A rat model of type 2 diabetes was established by high fat/sucrose diet
combined with intraperitoneal injection of small dose streptozotocin (STZ) .
Modeled rats were randomly divided into the model group, the ZQR group, and the
metformin group, 8 in each group. Eight rats were recruited as a normal control
group. ZQR at the daily dose of 12 g crude drugs/kg was administered to rats in
the ZQR group by gastrogavage. Metformin suspension at the daily dose of 150
mg/kg was administered to rats in the metformin group by gastrogavage. Equal
volume of distilled water was administered to rats in the normal control group
and the model group. All medication lasted for 12 weeks. The levels of fasting
blood glucose (FBG), free fatty acid (FFA), serum triglyceride (TG), serum total
cholesterol (TC), serum alanine aminotransferase (ALT), and aspartate
aminotransferase (AST) were detected. The body weight and wet liver weight were
weighed, and the liver weight index calculated. The liver TG content was
measured. The pathological changes of liver and the expression of SIK1 were
observed by HE staining and immunohistochemistry. The mRNA and protein expression
of SIK1 and SREBP-1c were detected using RT-PCR and Western blot. RESULTS:
Compared with the normal control group, FBG, FFA, TG, TC, ALT, AST, liver weight
index, and liver TG contents significantly increased (P < 0.01); liver steatosis
was severe, the mRNA and protein expression of SIK1 obviously decreased (P <
0.01); mRNA and protein expression of SREBP-1c increased (P < 0.01). After drug
therapy, compared with the model group, FBG, FFA, TG, TC, ALT, AST, and liver
weight index significantly decreased, liver TG contents significantly decreased,
the mRNA and protein expression of SIK1 obviously increased, while mRNA and
protein expression of SREBP-1c obviously decreased (P < 0.05, P < 0.01) in the
ZQR group and the metformin group (P < 0.05, P < 0.01); and the pathological
changes were also improved. All the indices were improved more in the ZQR group
(all P < 0.05). CONCLUSION: In this experiment, we found that the expression of
SIK1 decreased in NAFL rats with type 2 diabetes. ZQR could alleviate lesion of
NAFL type 2 diabetes rats possibly by up-regulating hepatic SIK1 expression at
mRNA and protein levels.
PMID- 25137853
TI - [Effect of Mudan Granule on islets beta cell function in monosodium glutamate
induced obese mice with insulin resistance: an experimental study].
AB - OBJECTIVE: To study the effect of Mudan Granule (MD) on the glucose metabolism
and beta cell function in monosodium glutamate (MSG) induced obese mice with
insulin resistance (IR). METHODS: MSG obese mice were induced by subcutaneous
injecting MSG (4 g/kg for 7 successive days in neonatal ICR mice). Forty MSG mice
with IR features were recruited and divided into four groups according to body
weight, fasting blood glucose, triglyceride (TG), total cholesterol (TC), and the
percentage of blood glucose decreased within 40 min in the IR test, i.e., the
model group (Con), the low dose MD group, the high dose MD group, and the
Metformin group (Met). Besides, another 10 ICR mice were recruited as the normal
control group (Nor). The water solvent of 2.5 g/kg MD or 5 g/kg MD was
respectively administered to mice in the low dose MD group and the high dose MD
group. Metformin hydrochloride was given to mice in the Met group at 0.2 g/kg
body weight. Equal dose solvent distilled water was administered to mice in the
Nor group and the Con group by gastrogavage, once per day. All medication was
lasted for 15 weeks. Insulin tolerance test (ITT) and oral glucose tolerance test
(OGTT) were performed after 6 weeks of treatment. Beta cell function was assessed
by hyperglycemic clamp technique. The morphological changes in the pancreas were
evaluated by hematoxylin-eosin (HE) staining. Changes of iNOS, NF-kappaB p65, and
p-NF-kappaB p65 in the pancreas were tested. RESULTS: Compared with the Nor
group, the blood glucose level, AUC, and fasting blood insulin, ONOO-contents,
iNOS activities, and the expression of iNOS, NF-kappaB p65 subunit, pNF-kappaB
p65 subunit obviously increased; decreased percentage of blood glucose within 40
min in ITT, glucose infusion rate (GIR), Clamp 1 min insulin, and Max-Insulin
obviously decreased in the Con group (P < 0.05, P < 0.01). Compared with the Con
group, the aforesaid indices could be improved in the Met group (P < 0.05, P <
0.01). In the low dose MD group, AUC, iNOS activities, and the expression of iNOS
and p-NF-kappaB p65 subunit obviously decreased; percentage of blood glucose
within 40 min in ITT and GIR obviously increased (P < 0.05, P < 0.01). In the
high dose MD group, AUC, ONOO-contents, iNOS activities, and the expression of
iNOS, NF-kappaB p65 subunit, and p-NF-KB p65 subunit obviously decreased;
percentage of blood glucose within 40 min in ITT, Max-Insulin, and GIR obviously
increased (P < 0.05, P < 0.01). CONCLUSION: MD could significantly improve IR and
functional disorder of 3 cells in MSG obese mice, which might be associated with
lowering inflammatory reaction in the pancreas.
PMID- 25137854
TI - [Roles of TRPV1 receptor in electroacupuncture regulating the jejunal motility of
mice: an experimental study].
AB - OBJECTIVE: To observe the intestinal movement of transient receptor potential
vanilloid 1 or vanilloid receptor 1 (TRPV1) knockout mice after stimulated by
electroacupuncture (EA), and to primarily explore the roles of TRPV1 receptor in
the jejunal motility regulated by acupuncture. METHODS: Normal wild-type CL57BL/6
and TRPV1 gene knockout mice were recruited in two groups, the B6 group and the
TRPV1 group, 15 in each group. The thermal threshold and the mechanical pain
threshold were respectively detected using JL-F digital photo thermal analyzer
instrument and ALMEMO2450 machine. The difference between the two thresholds were
compared. Meanwhile, a self-made pressure head was placed in the jejunum. The
internal pressure was monitored. When the pressure was stable, 2 mA 2/15 Hz EA at
Quchi (LI11), Tianshu (ST25), Shangjuxu (ST37), and Dachangshu (BL25) to observe
the changes of intestinal pressure value between before and after EA. The curve
of internal pressures was recorded. RESULTS: (1) The stimulation of light/heat
and mechanical stimulation were obviously slowed in the TRPV1 group than in the
B6 group (P < 0.01). (2) In the intestinal pressure observation experiment, the
bowel movement was not obviously seen in the two groups when acupunctured at
Quchi (LI11) and Shangjuxu (ST37) (P > 0.05). (3) Acupuncture at Tianshu (ST25)
and Dachangshu (BL25) of TRPV1 knockout mice could lead to intestinal movement (P
< 0.05), mainly inhibited bowel movement. The changing degree was equivalent to
that of B6 mice. CONCLUSIONS: Under the physiological condition, TRPV1 might be
mediated by thermal and mechanical stimulation. But TRPV1 mediated acupuncture
effect was quite complex, indicating TRPV1 mice might be one of intestinal
movement mediating factors.
PMID- 25137856
TI - [A blind technique used in randomized controlled trials of treatment based on
changes of syndromes].
AB - Treatment based on syndrome differentiation is an essential feature of
traditional Chinese medical diagnosis. The interventions based on changes of
syndrome types in randomized controlled trials are complicated, leading to the
difficulty of blind method enforcement. This article described a double-blind
method. It could be used in randomized controlled trials under the condition of
different syndrome types and different medications. It numbered drugs in two
stages, and in two phases to achieve double-blind. This method not only
guaranteed investigators and subjects to be in blinded conditions, but also
achieved using different medications for patients of different syndromes. It also
caused no drug waste. It was scientific and feasible.
PMID- 25137855
TI - [Prevention of Inonotus obliquus polysaccharides for high power microwave
radiation induced testicular injury in rats: an experimental research].
AB - OBJECTIVE: To investigate the effect of Inonotus obliquus polysaccharides on
testicular injury induced by exposure to high power microwave (HPM) in rats.
METHODS: A total of 30 male Wistar rats were randomly divided into 5 groups,
i.e., the normal control group, the microwave radiation model group, the
treatment group, the new microwave radiation model group, and the prevention
group, 6 in each group. All rats, except those in the normal control group, were
exposed to microwave at an average power density of 200 mW/cm2 for 6 min. Rats in
the control group and the model group were administered with normal saline by
gastrogavage, once a day. Rats in the treatment group and the prevention group
were given with Inonotus obliquus polysaccharides by gastrogavage, 2 mL each time
(400 mg/kg body weight), once a day. All rats were sacrificed on the 11th day.The
sperm density and the rate of sperm deformity were determined. Pathological
changes of testis were observed by light microscope and transmission electron
microscope. RESULTS: Short-term HPM irradiation could significantly reduce the
sperm density and increase the sperm deformity rate (P < 0.05). Meanwhile,
obvious pathological changes of testes occurred. Compared with the two model
groups, the sperm density increased and the sperm deformity rate decreased in the
treatment group and the prevention group (P < 0.05). Under the light microscope,
injuries of spermatogenic cells and stromal cells, as well as vascular dilatation
and congestion were obviously alleviated in the treatment group and the
prevention group. Mitochondrial swelling and endoplasmic reticulum expansion
shown by ultrastructural observation were also significantly alleviated. Of them,
injuries of spermatogenic cells and inflammation response were milder in the
treatment group than in the prevention group. CONCLUSIONS: Inonotus obliquus
polysaccharides had significant protective effect on microwave radiation induced
testicular injury. Better effect was obtained by therapeutic medication than
preventive medication.
PMID- 25137857
TI - [The application principle and strategies of transliteration in English
translation of Chinese medicine].
PMID- 25137858
TI - [The effectiveness and mechanism of Chinese medicine and pharmacy in intervening
myocardial fibrosis].
PMID- 25137859
TI - [An overviewn of integrative medical research of heart failure patients with
normal ejection fraction].
PMID- 25137860
TI - Preoxygenation-routine preoxygenation during induction and recovery from
anesthesia is recommended as a minimal safety precaution.
PMID- 25137861
TI - Fentanyl-induced cough--pathophysiology and prevention.
AB - Many reports have demonstrated that intravenous administration of a bolus of
fentanyl at induction of anesthesia can cause coughing with varying degrees. This
cough can be benign, but sometimes it causes undesirable side effects including
an increase in intraabdominal, intracranial or intraocular pressure. Many studies
demonstrated that the incidence and severity of fentanyl-induced cough could be
related to age, ethnicity, history of smoking, as well as to the rate, route,
dose and concentration of fentanyl administered. This cough was described by
several mechanisms including an inhibition of central sympathetic system leading
to vagal predominance, reflex bronchonstriction after the stimulation of
tracheobronchial tree receptors, or histamine release. The efficacy of several
measures to avoid fentanyl-induced cough have been demonstrated, and several
anesthetics adjuncts can be given prior to fentanyl administration aiming at
decreasing this unwanted side effect.
PMID- 25137862
TI - Cerebral "hyperoxygenation" with inhalational induction of anesthesia in
children: a retrospective comparison between vasoparalytic sevoflurane vs.
vasoneutral fentanyl.
AB - BACKGROUND: The higher levels of oxygen in cerebrum may contribute to neuro
apoptosis, analogous to direct tissue injury induced by toxic levels of oxygen.
Earlier report highlighted the possibility of cerebral "hyperoxygenation"
secondary to inhalational induction of anesthesia with sevoflurane in small
number of children. OBJECTIVE: The aim of this retrospective review was whether
similar cerebral "hyperoxygenation" trends can be seen in larger and
retrospective patients' database. METHODS: Data of patients who had undergone
cardiac surgeries at Children's Hospital during the two-year period (2010-2011)
was retrieved during this retrospective review: (a) stored computer data from
INVOS Cerebral/Somatic Oximeter for oximetry numbers and total duration of
oximetry monitoring, (b) paper chart perfusion records of the cardiac surgeries
for age and sex of the patient, urgency of the surgery, type of induction
(inhalational or intravenous), and total duration of cardiopulmonary bypass, (c)
general medical records for inpatient setting vs. outpatient setting of the
patient, and (d) anesthesia medical records for name of the medications used
during induction of anesthesia to segregate the patients who had fentanyl as a
lone induction agent and sevoflurane as a lone induction agent, for final
statistical calculations and analysis. For the two-year period (2010-2011), data
of 358 patients who had cardiac surgeries at Children's Hospital were reviewed.
However, after deletions of various patients' data due to various reasons, only
69 patients (0-4 years of age) who had sevoflurane induction were analyzed for
final statistical comparisons to 14 patients (0-4 years of age) who had fentanyl
induction. RESULTS: Cerebral and renal "hyperoxygenation" occurred during the
first 127 minutes with sevoflurane as compared to fentanyl though the percentage
changes from pre-induction values in oximetry during this time did not reach
level of significance. However, only cerebral "hyperoxygenation" persisted in the
last 127 minutes when patients had been induced with sevoflurane as compared to
fentanyl. CONCLUSION: Cerebral "hyperoxygenation" occurs with inhalational
induction of anesthesia with vasoparalytic sevoflurane in children 0 to 4 years
of age when compared to anesthesia induction with vasoneutral fentanyl.
PMID- 25137863
TI - Comparison between intravenous patient controlled analgesia and patient
controlled epidural analgesia in cirrhotic patients after hepatic resection.
AB - BACKGROUND: Postoperative pain is one of the most important problems that
confront surgical patients. The aim of this work is to compare pain control using
intravenous patient controlled analgesia (PCA) and patient controlled epidural
analgesia (PCEA) in cirrhotic patients undergoing elective hepatic resection.
METHODS: Thirty four adult patients ASAI and II scheduled for liver resection
were randomly allocated into two groups-Group (P) with I.V (PCA) with fentanyl
and Group (E) (PCEA) via epidural catheter using Bubivacaine 0.125% plus 2
microgram per ml fentanyl. Coagulation changes were followed and pain score was
compared in both groups. RESULTS: 34 child A cirrhotic patients, undergoing liver
resection were studied. The demographic data were comparable in both groups.
There was a significant decrease in pain score in both groups during the follow
up period when compared to their initial score. When comparing average pain score
between both groups, the PCEA group had significantly lower values. The changes
in prothrombin time (PT), INR, and hemoglobin (Hb), were significant all over the
follow up period compared to their corresponding base line values. 2 cases needed
FFP to normalize the INR for epidural removal. There was no significant
difference regarding postoperative nausea and vomiting (PONV) in both groups, no
clinical manifestation suggesting epidural hematoma, and no cases were recorded
to have respiratory depression. There were no significant differences in patient
satisfaction and ICU stay. CONCLUSION: The two modalities of pain control seems
to be nearly equivalent, but considering the risk of epidural catheter insertion
and removal in cirrhotic patients who are further exposed to hepatectomy with
subsequent additional coagulopathy, it may be wise to consider IVPCA technique as
a policy for pain management in cirrhotic patient undergoing hepatectomy.
PMID- 25137864
TI - Simulation training in endotracheal intubation in a pediatric residency.
AB - BACKGROUND: Airway management and endotracheal intubation are essential skills
for pediatric residents. Simulation-based technology is used for training
residents but it remains unclear whether high fidelity simulation results in
better retention of skills compared to low fidelity. The study assesses high
fidelity simulation of endotracheal intubation and traditional low fidelity
training in improving pediatric residents' knowledge retention and technical
skills; and if the difference translates into higher "real time" intubation
success rates. METHODS: Second and third year pediatric residents were randomized
into high fidelity (intervention) or low fidelity simulation (control) groups.
Airway management and intubation skills were taught using a didactic lecture and
demonstration on low fidelity mannequins. Knowledge was assessed before
randomization (T0) and 6 months after training (T6). Other outcome measures were:
1) airway management and intubation skills at T6 and T12 (12 months later) and 2)
successful intubation of actual patients by T12. RESULTS: 10 out of 11 residents
completed the intervention. Theoretical knowledge improved for both groups.
Participants made less mistakes (M) overtime: M (T0) = 3.2 and M (T6) = 2.6 for
the intervention group, and M (T0) = 4 and M (T6) = 2.40 for the control. There
was no significant effect of fidelity on intubation skills or the number of
successful intubations recorded in logbooks (allp > 0.05). In some instances
intubation skills showed regression over time. CONCLUSION: High fidelity
simulation showed no impact on residents' airway management and intubation
skills. Retention of theoretical knowledge persisted over time while practical
skills remained at baseline or declined.
PMID- 25137865
TI - A simple protocol to improve safety and reduce cost in hemodialysis patients
undergoing elective surgery.
AB - BACKGROUND: When patients with end-stage renal disease (ESRD) miss their routine
intermittent hemodialysis (IHD), electrolyte abnormalities and volume overload
often occur. An institutional protocol to ensure that patients receiving IHD have
elective surgeries scheduled within 24 hours after their dialysis may reduce
procedural delays or cancellations caused by hyperkalemia and hypervolemia after
a missed IHD session. The effect of this protocol was evaluated. METHODS: A
retrospective chart review was performed for ESRD patients receiving IHD who
underwent surgery from 6 months before to 6 months after the institutional
protocol was implemented. Preoperative potassium values, timing of IHD relative
to surgery, and the nature of surgery (elective or emergent) were documented. The
percentage of patients having IHD more than 24 hours before their elective
surgery was compared before and after protocol implementation. Average potassium
values were compared when IHD occurred within 24 hours vs. more than 24 hours,
using t test analysis. Cost associated with delay and cancellation for IHD was
also explored. RESULTS: Of the 15,799 cases performed, 190 involved ESRD patients
receiving IHD. Before the protocol, 32.1% of elective cases (n = 17) involved
patients scheduled for surgery more than 24 hours after IHD vs. 12.0% (n = 6)
after the protocol. Preoperative potassium values were less when patients
underwent IHD within 24 hours than at more than 24 hours (mean [SD], 4.32 [0.6]
mEq/L vs 4.63 [0.8] mEq/L; P = .03). CONCLUSIONS: The simple scheduling policy is
effective at reducing both cost and unnecessary perioperative risks for patients.
PMID- 25137866
TI - Emetogenicity-risk procedures in same day surgery center of an academic
university hospital in United States: a retrospective cost-audit of postoperative
nausea vomiting management.
AB - BACKGROUND: Despite the variable results of published studies, it is imperative
for ambulatory surgery centers to self-audit local cost-implications for post
operative nausea and vomiting (PONV) management. OBJECTIVE: Our retrospective
cost-audit assessed if there were comparative peri-anesthesia care cost-trends
among patients who had undergone Low-Emetogenicity-Risk Procedures (LERP),
Moderate-Emetogenicity-Risk Procedures (MERP) and Severe-Emetogenicity-Risk
Procedures (SERP). METHODS: This study was a review of Same Day Surgery Center
practices in an academic university hospital setting during a three-year period
(2010-2012). The patient lists were accessed from CIS and CITRIX App Bar for time
audit and OR (operating room) schedule reports. Subsequently, OR pharmacy
department ran a search for peri-operative anti-emetics and opioids that were
billed for the patients at Same Day Surgery Center for the review period. The
primary outcomes were the comparative costs/charges of these medications and
comparative durations/ charges for these patients' stay in the post-anesthesia
care unit (PACU). Secondary outcomes analyzed in the study included peri
anesthesia durations. RESULTS: A total of 8,657 patient records were analyzed.
Almost all analyzed variables revealed statistically significant inter-variable
positive correlations. The patients' age was significantly (P < 0.001) different
among LERP/MERP/SERP patients (LERP: 48.8 +/- 14.7 years; MERP: 61.8 +/- 14.6
years; SERP: 51.3 +/- 14.5 years). In regards to primary and secondary outcomes,
the statistical significant differences among LERP/MERP/SERP patients (after
correcting for both patients' age as well as patients' sex) were only achieved
for preoperative times (P = 0.002; Power = 0.9), operating room recovery times (P
= 0.003; Power = 0.9), PACU stay times (P < 0.001; Power = 1.0), and PACU charges
(P < 0.001; Power = 1.0). CONCLUSION: PACU stay times and PACU charges were
significantly higher in patients who had undergone SERP as compared to patients
who had undergone LERP or MERP at our Same Day Surgery Center.
PMID- 25137867
TI - The use of Airtraq laryngoscope versus Macintosh laryngoscope and fiberoptic
bronchoscope by experienced anesthesiologists.
AB - OBJECTIVE: The aim was to compare the hemodynamic parameters, intubation times,
upper airway trauma and postoperative sore throat scores of the patients with
normal airway anatomy, intubated with the Airtraq, Macintosh laryngoscope and
fiberoptic bronchoscope, by experienced anesthesiologists. METHODS: Ninety
patients, scheduled to undergo elective surgery under general anesthesia were
randomly divided into three groups (n = 30): Group A: Airtraq laryngoscope, Group
M: Macintosh laryngoscope and Group FB: fiberoptic bronchoscope. The time to
intubation and success rates were recorded. The hemodynamic parameters before and
one minute after the anesthesia induction were recorded and the measurements were
repeated 3, 4 and 5 minutes after the endotracheal intubation. The postoperative
sore throat scores and signs of any trauma were also recorded. RESULTS: Mean
arterial blood pressure and heart rate were not significantly different between
the three groups. The mean intubation time interval did not differ between
groups. Highest postoperative sore throat scores were recorded at the 6th hour
post extubation. The scores were 37.6 +/- 20.9 in Group A, 13.3 +/- 16.8 in Group
M and 13.6 +/- 14.0 in Group FB. The scores in Group A were significantly higher
compared to other groups. The number of patients requiring additional analgesia
to relieve sore throat was also significantly higher in Group A. CONCLUSION: The
Airtraq laryngoscope seems to be a more traumatic airway device in the routine
endotracheal intubation compared to Macintosh laryngoscope and fiberoptic
bronchoscope, when used by experienced anesthesiologists. It also does not offer
advantage over the first-attempt success rates, the intubation times and
hemodynamic parameters.
PMID- 25137868
TI - Ultrasound-guided regional anesthesia in a pediatric patient with acute
intermittent porphyria: literature review and case report.
AB - Ultrasound-guided regional anesthesia techniques placed under general anesthesia
have not been reported in pediatric patients with acute intermittent porphyria
(AIP). A 9-year-old male with AIP presented for right inguinal herniorraphy.
Family history included one relative's death after anesthesia. Preoperative
preparation included reviewing medications safe for AIP patients, minimizing
known AIP triggers (fasting, stress) and ensuring access to rescue medications.
Intraoperative management included a propofol induction with the patient's mother
present in the operating room. We performed an ultrasound-guided ilioinguinal
iliohypogastric nerve block under general anesthesia. The surgery proceeded
without complications and the patient did not demonstrate signs of an AIP crisis.
PMID- 25137870
TI - Unusually difficult intraesophageal bougie insertion in an intubated pediatric
patient.
PMID- 25137869
TI - Anesthetic considerations and management of a patient with unsuspected carcinoid
crisis during hepatic tumor resection.
AB - Anesthetic management for massive blood loss in liver surgery concomitant with
hemodynamic instability secondary to carcinoid crisis can be challenging in the
perioperative setting. Hypotension, diarrhea, facial flushing, bronchospasm, and
tricuspid and pulmonic valvular diseases are the common manifestations of
carcinoid syndrome. This report illustrates the importance of early recognition
and treatment for signs and symptoms of carcinoid syndrome not only in the
preoperative setting but also in the intraoperative phase to prevent undue
cardiovascular collapse.
PMID- 25137871
TI - Successful intubation using McGRATH MAC in a patient with Treacher Collins
syndrome.
PMID- 25137872
TI - Anesthesia care providers' based interdisciplinary peri-operative cross-over post
market--safety-surveillance: is it futuristic patient safety idea? Running title:
post-hire PMSS for interventionists.
PMID- 25137873
TI - Predictive factor for hepatic encephalopathy in cirrhotic patients who presented
with acute variceal bleeding.
AB - BACKGROUND: Cirrhotic patients who were hospitalized due to acute variceal
bleeding and subsequently developed hepatic encephalopathy during hospital stay
had dreadful outcome and high mortality rate. Recommendations regarding
management and prevention of encephalopathy in these patients are not available
in the current clinical practice guidelines. Defining high-risk patients could
possibly prevent or early detect hepatic encephalopathy and help develop
prophylactic management. OBJECTIVE: To evaluate the potential of certain clinical
predictors of hepatic encephalopathy in cirrhotic patients presented with acute
variceal bleeding. MATERIAL AND METHOD: The medical records of cirrhotic patients
with diagnosis of acute variceal bleeding by endoscopy were retrospectively
examined for clinical parameters. Potential predictive factors for hepatic
encephalopathy were identified by univariate and multivariate analysis. RESULTS:
One hundred seventy four cirrhotic patients who presented with acute variceal
bleeding were enrolled in the present study. Hepatic encephalopathy was developed
in 25 patients (14.4%). Multivariate analysis showed cirrhosis Child C, serum
potassium < 3.5 mmole/L, WBC > 10,000 cells/mm3, and hemoglobin < 8 gm/dL on the
day of admission were significant factors predicting hepatic encephalopathy in
cirrhotic patients presenting with acute variceal bleeding (adjusted odds ratio
36.7, 9.25, 4.91, and 4.52, respectively). Cirrhotic patients presented with
acute variceal bleeding who developed hepatic encephalopathy had higher rate of
infection (40% vs. 5.4%), respiratory failure (20% vs. 2%), unit of red blood
cell transfusion (3.8 +/- 1.8 units vs. 2.6 +/- 1.8 units), volume of fresh
frozen plasma transfusion (1,000 (0-4,000) cc vs. 500 (0-5,000) cc), length of
stay (9.0 +/- 3.5 days vs. 5.6 +/- 1.8 days), and mortality rate (8% vs. 0.7%),
than non-hepatic encephalopathy p-value < 0.05. CONCLUSION: Cirrhotic patients
presented with acute variceal bleeding with cirrhosis Child C, serum potassium <
3.5 mmole/L, WBC > 10,000 cells/mm3, and hemoglobin < 8 gm/dL were significant
predictors for development of hepatic encephalopathy. Cirrhotic patients with
acute variceal bleeding who developed hepatic encephalopathy had high morbidity
and mortality rates.
PMID- 25137874
TI - Short-term administration of an angiotensin II receptor blocker in patients with
long-term hemodialysis patients improves insulin resistance.
AB - BACKGROUND: Insulin resistance is commonly observed in uremic patients.
Angiotensin II receptor blockers (ARB) are reported to act as insulin sensitizers
in the animal model of hypertension and hypertensive patients. The authors
investigated the effects of valsartan on insulin resistance and glucose
metabolism in patients with long-term hemodialysis in the prospective, randomized
controlled study. MATERIAL AND METHOD: Thirty-three hemodialysis patients were
randomized into two treatment groups, valsartan 80 to 320 mg/day (n = 18) or non
renin-angiotensin-aldosterone-system blocking antihypertensive agents (control, n
= 15), treated for 12 weeks. Insulin resistance determined by homeostasis model
assessment (HOMA-IR), fasting plasma glucose (FPG), fasting plasma insulin, and
blood pressure monitoring were measured during the study. RESULTS: At baseline,
metabolic profiles did not significantly differ between the treatment and the
control groups. After 12 weeks of treatment, the valsartan group significantly
improved HOMA-IR from 2.6 +/- 0.9 to 2.3 +/- 0.7 (p = 0.041) and significantly
decreased FPG from 90.1 +/- 15.1 to 84.8 +/- 13.2 mg/dL (p = 0.008). In contrast,
the control group was not associated with any significant changes in HOMA-IR,
FPG, and fasting insulin levels. At the end of 12-week treatment, HOMA-IR, FPG,
and fasting insulin levels were not significantly different between the two
groups. CONCLUSION: These results indicate that the antihypertensive action of
valsartan improves glucose metabolism by improving the peripheral insulin
sensitivity in subjects with long-term dialysis.
PMID- 25137875
TI - The comparative study of diabetic specific formula and standard formula on
postprandial plasma glucose control in type 2 DM patients.
AB - OBJECTIVE: To compare the postprandial plasma glucose level after diabetic
specific formula (DSF) and standard formula (SF) administration in type 2
diabetic patients. MATERIAL AND METHOD: Thirty type 2 diabetic patients were
included in the present randomized, controlled, double-blind, cross-over study.
Subjects received DSF and isocaloric SF as a bolus administration of 400 mL while
continuing their anti-diabetic medications. Venous blood samples were collected
and analyzed to assess plasma glucose levels at pre- and at 30, 60, 90, 120, and
180 min post-administration of the formulas. RESULTS: Postprandial glucose
profiles were significantly lower with DSF compared to SF administration
determined as a mean glucose concentration at 2-hour post-administration. The
glucose area under the curve (AUC) after DSF consumption was 33% lower than the
AUC after SF consumption, p < 0.001. CONCLUSION: Use of DSF resulted in a
significantly lower postprandial rise in plasma glucose concentrations than using
SF. It should be the preferred option in diabetic patients who need nutritional
support.
PMID- 25137876
TI - The reliability of calculated low-density lipoprotein cholesterol from four
different formulas in Thai diabetic patients.
AB - BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is usually calculated by
the Friedewald formula but it has certain limitations, especially in
hypertriglyceridemia and diabetes mellitus (DM). OBJECTIVE: Assess the
reliability of LDL-C levels calculated from four formulas (Friedewald, Anandaraja
and colleagues, Chen et al, and Vujovic et al) when compared to direct LDL-C
measurement (dLDL-C) in DM with various triglycerides (TG) levels. MATERIAL AND
METHOD: The present study included 2,967 fasting Thai diabetic patients with TG
levels less than 400 mg/dl. The total cholesterol and TG levels were measured by
enzymatic colorimetric assay. The high-density lipoprotein cholesterol and dLDL-C
levels were measured by homogeneous enzymatic colorimetric assay. The calculated
LDL-C (cLDL-C) from each formula was compared to dLDL-C. In addition, the degree
of agreement between the methods was assessed. RESULTS: The mean and standard
deviation (SD) of dLDL-C was 122.3 (37.1) mg/dl, the mean (SD) of cLDL-C from the
formula of Friedewald (F-LDL-C), Anandaraja and colleagues, Chen et al, and
Vujovic et al (Vu-LDL-C) were 115.2 (35.8), 120.8 (35.2), 116.6 (34.2), and 123.9
(37.4) mg/dl, respectively. In aspect of the accuracy defined as the percentage
of dLDL-C minus the cLDL-C within -10 to 10 mg/dl; the accuracy of Vu-LDL-C were
higher than the other cLDL-C in overall and the most of subgroups of TG levels,
except in the subgroup of TG levels < 100 mg/dl which the accuracy of F-LDL-C was
the highest. The overall number of dLDL-C minus Vu-LDL-C within -10 to 10 mg/dl
was 2,655 cases (89.5% with p < 0.001). The Vu-LDL-C showed a little discordance
with dLDL-C at the higher levels of TG. All cLDL-C had systematic differences
from dLDL-C, while only Vu-LDL-C had no proportional difference. The Vu-LDL-C
yielded the lowest mean of difference between dLDL-C and cLDL-C of -1.60 with SD
of 6.31 mg/dl, while F-LDL-C yielded the highest value of 7.06 with SD of 7.91
mg/dl. The Vu-LDL-C had the narrowest range of 95% limits of agreement (-13.97 to
10.77 mg/dl) and the difference neither depended on the magnitude of LDL-C
measurements nor had proportional error. CONCLUSION: The modified Friedewald
formula of Vujovic et al provided the most accuracy with acceptable degree of
agreement in DM compared to those derived from the original Friedewald formula or
the others. The interference caused by hypertriglyceridemia was obviously
diminished; thus, the formula of Vujovic et al is more reliable than the others
in DM if TG levels are range from under 400 mg/dl to 100 mg/dl.
PMID- 25137877
TI - Experience with surgical treatment of retroperitoneal soft tissue sarcomas at a
university hospital in Thailand.
AB - BACKGROUND: Retroperitoneal soft tissue sarcomas (RSTS) are rare malignant tumors
with a distinguishing feature of slow growth in the silent retroperitoneal space.
The patients usually present late with a large retroperitoneal mass surrounded by
the major vascular structures and visceral organs rendering curative resection an
extremely difficult and risky operation. The purpose of the present study was to
demonstrate surgical experience and results of treatment of RSTS at King
Chulalongkorn Memorial Hospital. Operative techniques of these complex surgical
procedures were also described. MATERIAL AND METHOD: A retrospective study was
performed in patients who had RSTS and underwent surgical resection between June
2003 and November 2011 at King Chulalongkorn Memorial Hospital, Bangkok,
Thailand. All patients were followed after the operations until death or last
follow-up at the out-patient clinic in October 2012. Data collection included
demographic data, details of operations, operative complications, neoadjuvant and
adjuvant chemoradiation therapy, local recurrence, treatment of local recurrence,
and 5-year overall survival rate. Factors associated with local recurrence were
also examined. RESULTS: During the 9.4-year period, 18 patients entered into the
present study. Fourteen (77.8%) were female and four (22.2%) were male. The age
ranged from 44 to 80 years (median 53.5 years). Duration of symptoms ranged from
one week to 24 months (median 3.5 months). The tumor size ranged from 10 to 48 cm
(median 27 cm) in greatest dimension. All patients underwent preoperative CT
scan. Preoperative core needle biopsy was performed in one patient. One patient
had preoperative radiation therapy. Sixteen patients (88.9%) underwent complete
gross resection (CGR) (R0 or R1 resection) and two (11.1%) had palliative
resection (R2 resection). All patients who had CGR (n = 16) had one or more
contiguous organ resection (kidney 87.5%, colon 50%, or adrenal gland 43.7%). The
operative time ranged from 120 to 360 minutes (median 330 minutes). The operative
blood transfusion ranged from 0 to 12 units (median 2.5 units). Postoperative
bleeding complication requiring reoperation occurred in three patients (16.7%).
One patient had postoperative uncomplicated pancreatic fistula. There was no
perioperative mortality. The final pathological reports were liposarcoma in 15
patients (83.3%). Other histology were atypical lipomatous tumor malignant
fibrous histiocytoma, and unspecified spindle cell tumor in one patient each. Two
patients who had palliative resection died at six and 16 months after the
operations. Local recurrence occurred in five patients who had CGR (31.3%). One
of them died at 60 months after the operation. The median follow-up time in
patients who underwent CGR was 39.5 months (range 12-114 months). The 5-year
overall survival of the entire cohort was 73.5% (95% CI: 44.3-88.4%). The 5-year
overall survival of patients who had CGR was 83.3% (95% CI: 53.5-98.5%).
Univariate analysis of the tumor size, tumor grading, status of the surgical
margins, and primary operation or re-resection revealed no statistical
significance in patients who had CGR with and without local recurrence.
CONCLUSION: Acceptable outcomes after complete surgical resection of the RSTS
were achieved from this small but important case-series. The authors have
demonstrated that CGR with concomitant resection of the contiguous organs can be
safely performed in patients with large RSTS. Preoperative CT scan was invaluable
for diagnosis and treatment plan. Preoperative core needle biopsy was not
necessary when preoperative CT scan was diagnostic. Intention for curative
resection should be attempted whenever possible to minimize chance of local
recurrence and improve survival. Experience of the surgical team is an important
factor for successful results when conducting these technically demanding
operations.
PMID- 25137878
TI - Reliability of a Thai version of the International Prostate Symptom Score (IPSS)
for the Thai population.
AB - OBJECTIVE: To develop and test the reliability of a Thai version of the
International Prostate Symptom Score (IPSS-Th). MATERIAL AND METHOD: A Thai
version of the International Prostate Symptom Score (IPSS-Th) was developed after
conducting many steps. The original English version of the International Prostate
Symptom Score (IPSS) was translated into Thai by three urologists working
independently. After having compared the original English version with various
translations, the final Thai version was obtained. Fifty Thai males possessing a
good understanding of both English and Thai were asked to complete the Thai
version of the IPSS. Two weeks later, they were asked to complete the English
version of the IPSS. Internal consistency was assessed using Cronbach's alpha.
Next, 118 Thai males were tested using the Thai version of the IPSS and retested
after two weeks. As such, the reliability of the Thai version of the IPSS was
evaluated using the test-retest method. RESULTS: For the Thai IPSS version,
Cronbach's alpha was 0.77 and the English version of the IPSS was 0.88. The test
retest reliability was 0.96. CONCLUSION: The Thai version of the IPSS was found
to be reliable and should be a useful tool for patient assessment, follow-up, and
research in the population of Thai-speaking patients.
PMID- 25137879
TI - A prospective analytical study of the effects and adverse events of alendronate
(Aldren70) treatment in Thai postmenopausal women.
AB - OBJECTIVE: To elucidate the efficacy and adverse events of alendronate (Aldren70)
after 12 months of treatment in 50 to 70 years old postmenopausal women. MATERIAL
AND METHOD: The authors observed 50 postmenopausal women who had clinical
conditions of osteopenia or osteoporosis and had never been treated with
alendronate acid. Bone mineral density (BMD) of L1-L4, the left hip, and the left
forearm were performed at the initial assessment and after 12 months of
treatment. The serum levels of osteocalcin (OC), procollagen type 1 N-terminal
propeptide (PINP) and beta-crosslaps (beta-CTx) were performed at the baseline
and then after 3 months, 6 months and 12 months of treatment. The data were
analyzed using the SPSS software. Paired t-test was used to compare lumbar spine,
hip and forearm before and after treatment. RESULTS: Treated by using Aldren70
once weekly for one year the BMD of the lumbar spine increased highly up to
11.26% (g/cm2) and 25.82% (T-score) from the base line (p < 0.001 and p < 0.001,
respectively). On the other hand, the change in BMD of the left hip increased
17.54% (g/cm2), 8.2% (T-score), at the left forearm increased 3.96% (g/cm2),
7.62% (T-score) after 12 months respectively. There was significant increase of
BMD between before and after 12 months. The mean values of bone markers at the
0.05 level before treatment, three months, six months, and 12 months of treatment
in osteocalcin were 0.2813, 0.1242, 0.896, and 0.0889 ng/ml respectively. The
PINP were 36.1762, 19.3894, 14.3084, and 15.1260 ng/ml respectively. Beta
crosslaps were 0.2813, 0.1242, 0.0896, and 0.0889 ng/ml respectively. Adverse
events found in five patients were the symptoms of stomachache (2.4%),
constipation/diarrhea (1.2%), palpitation (1.2%), and muscle/bone pain (1.2%).
CONCLUSION: The generic alendronate (Aldren 70) in our clinical trial was found
to be highly effective at the spine concerning the bone mass improvement and less
at the hip and wrist joints in comparison. All the result figures met the
standard efficacy after 12 months follow-up by increasing bone mass and reducing
serum bone markers.
PMID- 25137880
TI - Acetabular cup placement in navigated and non-navigated total hip arthroplasty
(THA): results of two consecutive series using a cementless short stem.
AB - BACKGROUND: Acetabular component malposition has been linked to increased rates
of dislocation, impingement, pelvic osteolysis, cup migration, leg length
discrepancy and polyethylene wear in patients undergoing total hip arthroplasty
(THA). OBJECTIVE: Compare the acetabular component positioning and the operative
time in two consecutive short-stem cementless THA series without and with using
an imageless navigation. MATERIAL AND METHOD: The retrospective study consisted
of 31 cases of short-stem cementless THA without navigation (NNAV) and 30 cases
with navigation (NAV). CT scans were performed in all cases at two-month or later
postoperatively. The abduction and anteversion angles measured on postoperative
CT were compared between two groups using t-test. The percentage of cup placement
(abduction, anteversion and combined) within the safe zone for each group was
compared using Chi-square test at a 0.05 level of significance. The operative
time was compared between two groups using t-test. RESULTS: The mean abduction
was 43.97 (range, 33-52, SD 4.44) in NNAV group and 41.37 (range, 37-45, SD 2.01)
in NAV group. This difference was significant (p = 0.004). The mean anteversion
was 22.58 (range, 2-39, SD 10.68) in NNAV group and 13.57 (range, 7-18, SD 3.28)
in NAV group. This difference was significant (p < 0.001). According to the
criteria of Lewinnek et al, 96.8% in NNAV group were placed within the safe zone
for abduction, 51.6% for anteversion, and 48.4% for both abduction and
anteversion. In NAV group, all 30 cups (100%) were placed within the safe zone
for abduction, anteversion, and both. There were significant differences in the
percentage of cup placement within the safe zone for anteversion (p < 0.001), for
both abduction and anteversion (p < 0.001) but not significant for abduction (p =
0.32) between two groups. The mean operative time was 107.09 and 110.67 minutes
for NNAV and NAV group respectively, this difference was not significant (p =
0.49). CONCLUSION: The present study demonstrated a significant increase in the
placement of acetabular cups within the safe zone using imageless navigation
compared to freehand technique, especially at anteversion angle.
PMID- 25137881
TI - Prevalence of atypical femoral fractures in Thai patients at a single
institution.
AB - OBJECTIVE: Evaluate the prevalence of atypical femoral fracture (AFF) in Thai
patients at a single institution based on the 2010 and 2013 American Society of
Bone and Mineral Research (ASBMR) criteria and the sensitivity and specificity of
each radiographic feature of AFF to identify bisphosphonate treatment. MATERIAL
AND METHOD: The authors retrospectively reviewed plain radiographs of 856
patients who were diagnosed with subtrochanteric or femoral shaft fractures
between 2002 and 2013. Only those who had major radiographic features of AFF
according to the 2010 ASBMR criteria were included. Next, the prevalence of
atypical fracture was recalculated based on the revised 2013 ASBMR criteria.
Furthermore, the specificity and sensitivity of each radiological finding to
detect bisphosphonate treatment were calculated. RESULTS: The prevalence of
atypical femoral fracture based on 2010 ASBMR criteria at this institution was
5.7%. Two patients had all radiographic features of AFF but sustained a high
energy trauma and could be diagnosed with AFF based on the 2013 ASBMR criteria.
Among all of the radiographic features to define AFF, a localized periosteal
thickening of the lateral femoral cortex was the most specific sign to detect
bisphosphonate treatment (0.98; 95% CI 0.96-0.99). CONCLUSION: The prevalence of
AFF in Thai patients at a single institution was approximately 6%. Although the
prevalence of AFF did not dramatically change after applying the 2013 revised
ASBMR criteria, this reflected some gap in the diagnosis criteria, which should
require further refinement. The authors suggested that the ASBMR criteria should
be used only with those having acute fractures.
PMID- 25137882
TI - Diagnostic properties of the STOP-Bang and its modified version in screening for
obstructive sleep apnea in Thai patients.
AB - OBJECTIVE: To test the diagnostic properties of the original and a modified STOP
Bang, as well as testing the additional use of a waist-to-height ratio (WHtR) of
> or = 0.55 in screening for obstructive sleep apnea (OSA) in Thai patients.
MATERIAL AND METHOD: Three hundred and three patients (186 males and 117 females)
who underwent anthropometric measurement and standard polysomnography were asked
to complete the STOP-Bang questionnaire. Subjects were considered high-risk if
their scores were > or = 3. Patients with significant co-morbidities were
excluded. RESULTS: Screening for OSA involved measurements of STOP-Bang
sensitivity, specificity, positive predictive value, and negative predictive
value at several apnea-hypopnea index (AHI) cut-off points. At AHI 5, these
values were 87.3%, 48.1%, 82.2%, and 52.2%, respectively. At AHI 15, these values
were 92.6%, 36.4%, 58.5%, and 83.6%, respectively. The modified STOP-Bang (using
a cut-off of BMI > 30 kg/m2) showed slightly increased sensitivities at the AHI
cut-off points of 5 and 15 with values of 88.7% and 93.2%, respectively, with
improved area under the curves. Furthermore, by applying the WHtR of > or = 0.55
to those patients who were classified as high-risk by the questionnaires, the
specificities for predicting OSA were improved to 85.2% and 76.1% for the
aforementioned cut-off points, respectively. CONCLUSION: Both STOP-Bang and its
modified version were highly sensitive measures for OSA screening in medical or
dental clinics. However, the modified version might be more suitable for Thais
and Asians, and the additional use of WHtR > or = 0.55 might be useful for
reducing the unnecessary sleep investigation or management in those who were
classified as high-risk patients.
PMID- 25137883
TI - Clinical outcome of postoperative radiotherapy with or without chemotherapy in
adult glioblastoma multiforme in Ramathibodi Hospital: a retrospective study.
AB - OBJECTIVE: To identify the treatment outcome of glioblastoma multiforme (GBM) in
Ramathibodi Hospital from overall survival rate and related prognostic factors.
MATERIAL AND METHOD: Medical records of patients with histological diagnosis of
GBM treated at Radiation Oncology Division, Radiology Department, Ramathibodi
Hospital between 2000 and 2010 were reviewed and available data extracted for
evaluation of treatment outcome. RESULTS: There were 47 patients with mean age at
diagnosis of 51.9 years (range from 18 to 82 years). Surgery (partial 76.6%,
total 12.8%, and biopsy 10.6%) followed by postoperative radiotherapy (mean dose
52 gray) was the treatment of choice with or without concurrent and adjuvant
Temozolomide (TMZ). With median follow-up time of 0.9 years, the median survival
of the patients was 2.1 years (95% CI 1.08-7.36), whereas one and two-year
overall survival rates were 78.0% and 57.8%, respectively. In univariate
analysis, persistent neurological deficit after surgery and presenting symptom of
visual disturbance were identified to lower overall survival while multivariate
analysis, younger age, and higher radiation dose were identified as favorable
prognostic factors to improve overall survival. Re-surgery or re-irradiation in
some selected cases of recurrent or progressive disease was considered as a
choice for palliative treatment. CONCLUSION: Proper management of GBM patient was
surgical removal and postoperative radiotherapy with or without chemotherapy.
Proper palliative treatment modality was considered in selected cases of
recurrent or progressive disease.
PMID- 25137884
TI - Committed suicide: forensic autopsy analysis at Ramathibodi Hospital during year
2001-2010.
AB - BACKGROUND: Suicide is one of the most important causes of death in the world. To
study the behaviors and risk factors may be helpful to prevent suicide.
OBJECTIVE: To retrospectively study the factors that affected suicide in forensic
postmortem cases at Ramathibodi Hospital, Bangkok, Thailand between 2001 and
2010. MATERIAL AND METHOD: Two hundred ninety suicidal cases from 7,102 forensic
postmortem autopsies in Ramathibodi Hospital between 2001 and 2010 were
descriptively retrospective studied. Study topics included sex, age, nationality,
year, methods of suicide, and HIV. RESULTS: The suicide-rate in the present study
varied between 2.53% and 6.91% (average 4.08%) of the forensic autopsy cases. The
peak was found in 2003. Males had higher suicide rate than females [ratio of M:F
of 4.3:1 (235 males and 55 females)]. The age varied from seven years to 91
years. Although the average age of suicide was 37.38 years, the peak was found in
the young adult (age group of 21 to 30 years). Male, younger age, and foreigner
were related to suicide with statistical significance. Hanging was the most
frequent method of suicide followed by fall from height (62.1% and 17.2%
respectively) and by firearm (in male) and toxic substance ingestion (in
females). Of all the suicide, 5.1% were HIV seropositive, which is slightly more
than non-HIV cases (4.0%) but this was not statistically significant. CONCLUSION:
The suicidal cases among unusual death were related to varieties of factors.
Male, younger age, and foreigner were significant related to suicide. Hanging and
falling from height were the most frequent method of suicide.
PMID- 25137885
TI - Necrotizing fasciitis: a rare manifestation of late-onset neonatal group B
streptococcal infection.
AB - Preterm infants have a risk factor of developing late-onset group B streptococcal
(GBS) infection. A 62-day-old infant who was a former 25-week male infant
presented with fever and an erythematous, warm and tender, soft tissue swelling
in the right submandibular region. He was diagnosed with cellulitis. Within 72
hours, his lesion had rapidly progressed to necrotizing fasciitis. His blood
culture grew penicillin-sensitive GBS. This reported case illustrates necrotizing
fasciitis as a rare manifestation of late-onset neonatal GBS infection.
PMID- 25137887
TI - President's update. Leading the way in primary health care.
PMID- 25137886
TI - Paget's disease of bone in ethnic Thai presented with urologic symptoms and
misleading as metastatic prostate cancer: report of a case with a review of the
literature.
AB - Paget's disease of bone is common in some parts of Europe and in countries
inhabited by European emigrants. In Western Countries, Paget's bone disease is
one of the priorities in differential diagnosis for elderly patients who present
osteoblastic lesions, so it is unlikely to be overlooked, even though patients
may present symptoms unrelated to bone lesions. However in Asian countries where
Paget's disease is rare, metastatic prostate cancer appears to be the most common
cause for osteoblastic lesions, thus, the Paget's disease is unlikely to be of
much concern. This may lead to undue emphasis on investigations to support the
diagnosis of prostate cancer. In this report, a 69 year-old man presented pain in
the right leg and difficulty urinating. The plain film showed osteoblastic
lesions of the right pelvic bone and lumbar spine. The pertinent routine
laboratory findings revealed increased levels of serum alkaline phosphatase 125
U/L (normal 27-86). Metastatic prostate cancer was highly suspected and
investigations focused upon this, including a serum prostate specific antigen
assay, a transurethral cystoscopic examination, an intravenous pyelogram, and an
ultrasonogram of the prostate gland. However all of these investigations failed
to support prostate cancer. Bone biopsy was performed twice, resulting in a
report supporting Paget's disease of bone. The patient was treated with
alendronate for three months. Radiologic findings, six months later, showed signs
of improvement. He died one year later of heart failure that could plausibly had
been a cardiovascular complication of Paget's disease. Better awareness of
Paget's disease in Thailand and other Asian countries should reduce the incidence
of unnecessary investigations and avoid a misleading diagnosis, which could lead
to inappropriate treatment for metastatic prostatic cancer and undesirable
psychological impact associated with being misinformed regarding malignancy.
PMID- 25137888
TI - Clarification on breastfeeding article from previous issue.
PMID- 25137889
TI - Response from author.
PMID- 25137890
TI - Nursing's purpose.
PMID- 25137891
TI - Can decreasing antipsychotic use lead to growth in mental and emotional health?
PMID- 25137892
TI - Assignment of Client Care Guidelines enhanced to focus on leadership of RN role.
PMID- 25137893
TI - An interview with Deputy Minister Janet Davidson.
PMID- 25137894
TI - Every nurse a leader.
PMID- 25137895
TI - Radiology. In search of a clear picture.
PMID- 25137896
TI - On centralisation versus localisation. Stop one-track thinking to boost public
support.
PMID- 25137897
TI - Our safe staffing guidance is based on strong evidence.
PMID- 25137899
TI - A Tory manifesto should not be conservative. How the NHS divides the Tories.
PMID- 25137898
TI - Put the constitution on the front line.
PMID- 25137900
TI - Imaging. Putting PET CT to the test.
PMID- 25137901
TI - Patients experience. Give patients a valid voice to broadcast.
PMID- 25137902
TI - Acute care. A&E needs more than a sticking plaster solution.
PMID- 25137903
TI - Commissioning. Come together to put cancer care on the right path.
PMID- 25137904
TI - Unraveling the mystery of MU audits. 7 strategies to protect your practice.
PMID- 25137905
TI - Managing transitions of care. Effective care transition management is a key to
achieving value-based care for your patients.
PMID- 25137906
TI - 4 ways to protect your practice's schedule against emergencies.
PMID- 25137907
TI - Post-implementation: making the EHR system work for you.
PMID- 25137908
TI - Only credentialed medical assistants can enter EHR orders.
PMID- 25137909
TI - Handling high-deductible patients requires communication, policies.
PMID- 25137910
TI - Protect your assets by incorporating your practice.
PMID- 25137911
TI - Preventing and treating COPD.
PMID- 25137912
TI - How important are young adults to the ACA's insurance exchanges?
PMID- 25137913
TI - Comparative analysis of early distance visual acuity in patients after coaxial
phacoemulsification through the micro-incision (1.8 mm) and after standard
phacoemulsification through the small incision (2.75 mm).
AB - INTRODUCTION: The purpose of the study was to evaluate early postoperative visual
acuity outcomes of coaxial phacoemulsification with a foldable intraocular lens
implantation, performed through a 1.8 mm wide clear corneal microincision (C
MICS) and to compare it with standard phacoemulsification through a 2.75 mm
incision. MATERIAL AND METHODS: The examined group consisted of a non-randomised,
prospective series of 130 eyes of 130 patients who underwent coaxial 1.8 mm
microincision cataract surgery with foldable intraocular lens implantation (MI60,
Bausch & Lomb). The reference group comprised 123 eyes of 123 patients who
underwent standard phacoemulsification through the 2.75 mm incision with foldable
intraocular lens implantation (Akreos Adapt AO, Bausch & Lomb). The following
parameters were evaluated preoperatively and one day after the surgery: distance
uncorrected visual acuity, distance best corrected visual acuity, intraocular
pressure, anterior and posterior segment of the eye. All patients were divided
into groups according to the LOCS III scale. RESULTS: The improvement of distance
uncorrected visual acuity and distance best corrected visual acuity was observed
postoperatively in both groups. The mean uncorrected visual acuity in the
examined group was significantly better than in the reference group on the first
postoperative day (0.88 +/- 0.18 vs 0.79 +/- 0.26). CONCLUSIONS: The early
postoperative visual acuity results of C-MICS were better than the results of
standard small incision phacoemulsification. As far as fast visual rehabilitation
after MICS is concerned, the early uncorrected visual acuity should be considered
as an important yardstick in measuring success in cataract surgery. These results
are due to the MICS technique, which seems to be the minimally invasive surgery,
and should be regarded nowadays as a procedure of choice.
PMID- 25137914
TI - In vivo imaging of the mouse retina using high-resolution optical coherence
tomography.
AB - PURPOSE: In this study, we demonstrate the advantages of high-resolution optical
coherence tomography for the non-invasive, in vivo, three-dimensional imaging of
the mouse retina. METHODS: High-resolution optical coherence tomography images of
the mouse retina were acquired using the Bioptigen Envisu R2200-HR SD-OCT system.
We measured the retinal thickness and compared the measurements to those obtained
using conventional histology techniques. RESULTS: High-resolution spectral-domain
optical coherence tomography enables high-quality in vivo visualization of
retinal structures in mice, providing an accurate quantitative description of
retinal layers. Additionally, the ultra-high-speed system offers many advantages
over histology, e.g., it permits the visualization of retinal microvasculature
and pulsatile flow dynamics. CONCLUSIONS: Spectral domain optical coherence
tomography is a new important tool for the in vivo analysis of mouse eyes.
PMID- 25137915
TI - [Increased expression of endothelin-1-- a novel diagnostic marker for early AMD
detection?].
AB - AIM: The relationship between ischemic vascular disease and age-related macular
degeneration may indicate the role of vascular injury as the primary insult
causing functional deficits in age-related macular degeneration. The vasoactive
factors produced by endothelial cells include endothelin-1 (ET-1), which is one
of the most potent vasoconstricting peptides. In this study we sought to explore
the potential role of endothelial dysfunction in the pathogenesis of age-related
macular degeneration by measuring the concentration of ET-1 in peripheral blood
of individuals diagnosed with age-related macular degeneration and evaluating its
intracellular expression in peripheral blood cells, on mRNA level. MATERIAL AND
METHODS: Peripheral blood samples from 31 patients with diagnosed dry age-related
macular degeneration and 46 patients with neovascular age-related macular
degeneration were collected. Forty six age- and sex-matched volunteers without
age-related macular degeneration were enrolled as a control group. ET-1 plasma
levels were analyzed by ELISA and intracellular expression of ET-1 in peripheral
blood cells was studied by using qRT-PCR. RESULTS: The expression of
intracellular ET-1 was significantly elevated in peripheral blood cells of both
dry and wet age-related macular degeneration patients compared with the control
subjects. Immunofluorescence staining revealed that ET-1 was specifically
expressed in the circulating endothelial cells. CONCLUSIONS: We assume that
damaged endothelial cells may release a variety of vasoconstricting molecules,
including ET-1, leading to derangement between the endothelium-derived relaxing
and contracting factors. Local retinal ischemia consequently develops which may
promote the development of retinal degeneration in patients with age-related
macular degeneration,
PMID- 25137916
TI - Bilateral serous retinal detachment in preeclampsia--a case report.
AB - Preeclampsia is a leading cause of maternal and fetal/neonatal mortality
worldwide. Serous retinal detachment is an unusual cause of visual loss in
pregnancy. This is a case report of a 17-year-old patient who was admitted to the
obstetric ward with symptoms of preeclampsia. The pregnancy was terminated by
cesarean section at 38 gestational weeks. The patient complained of blurred
vision in both eyes throughout the perinatal period. The ophthalmic examination
revealed serous retinal detachment in both eyes. The optical coherence tomography
demonstrated the hyporeflective area between the retinal pigment epithelium and
the neurosensory retina. With blood pressure control at postpartum, there serous
retinal detachment resolved spontaneously and patient's vision improved.
PMID- 25137917
TI - Multifocal syphilitic chorioretinitis--a case report.
AB - The aim of the paper is to report a case of a 22-year-old male patient with
chronic bilateral uveitis and retinitis secondary to syphilis. Until the
diagnosis, the patient had been treated symptomatically with ceftriaxone which
resulted in visual acuity improvement. The patient was referred to the Sexually
Transmitted Disease Clinic for causal treatment after which he did not continue
further ophthalmic monitoring. After a year he contacted the Department again due
to vision deterioration and a relapse of retinitis and choroiditis was diagnosed.
The patient was referred to the Sexually Transmitted Disease Clinic for causal
treatment which he never received as he did not present there. Since the
beginning of the 21st century the incidence of syphilis has significantly
increased. Although it is an infectious disease with potentially permanently
debilitating effect e.g. on vision, its treatment is not compulsory in Poland.
Infectious etiology and primary syphilis should always be considered in patients
with progressive retinitis, choroiditis and vitritis.
PMID- 25137918
TI - [Photodynamic therapy in a patient with chronic central serous chorioretinopathy-
a case report].
AB - PURPOSE: The aim of the study was to evaluate the efficacy of photodynamic
therapy as the treatment of chronic central serous chorioretinopathy. MATERIAL
AND METHODS: A 59-year-old man was referred to the Department of Ophthalmology
and Ocular Oncology, Jagiellonian University in Cracow with a complaint of
recurrent visual acuity impairment in his left eye, which he had noticed for the
first time three years earlier. The complete ophthalmic examination was extended
by the additional diagnostic procedures of optical coherence tomography and
fluorescein angiography and the patient was diagnosed with chronic central serous
chorioretinopathy. He was eligible for the photodynamic therapy with a full dose
of verteporfin, which was performed. The patient was subsequently re-assessed at
3 and 6 months following treatment completion. During the follow up assessment
the amount of subretinal fluid on fundus examination and the best-corrected
visual acuity (Snellen) were evaluated. The follow up optical coherence
tomography was also performed. RESULTS: Six months after photodynamic therapy the
subretinal fluid resolved completely, the distance best-corrected visual acuity
improved from 0.2 to 0.5 and the near best-corrected visual acuity from 2.25 to
0.5. No treatment-induced adverse effects were observed. CONCLUSION: The
photodynamic therapy may be effective in the management of selected cases with
chronic central serous chorioretinopathy. central serous chorioretinopathy,
photodynamic therapy.
PMID- 25137919
TI - [Leukoaraiosis as a cause of non-arteritic anterior ischemic optic neuropathy--a
case report].
AB - The paper presents the case of a 61-year-old man with specific symptoms of non
arteritic anterior ischemic optic neuropathy. The head computed tomographyscans
revealed multiple leukoaraiotic lesions. Leukoaraiosis is a disease affecting
small cerebral vessels. Its pathogenesis is associated with a chronic
inflammatory process and ischemic vascular endothelial dysfunction which reduce
the cerebral blood flow. It cannot be ruled out that this process, alongside with
Horton disease, hypertension, diabetes and atherosclerosis, may also be involved
in the pathogenesis of non-arteritic anterior ischemic optic neuropathy.
leukoaraiosis, non-arteritic anterior ischemic optic neuropathy.
PMID- 25137920
TI - [Idiopathic choroidal neovascularization--case report].
AB - PURPOSE: To report a patient with peripapillary idiopathic choroidal
neovascularization treated with an anti-VEGF (anti- vascular endothelial growth
factor) agent (bevacizumab) observed during for 9 months. PATIENT AND METHODS:
Twenty nine years old man was referred to the Department for diagnosis and
treatment because of unilateral visual acuity decrease in the right eye (VA RE-
0.1) and metamorphopsias. The routine ophthalmic examination revealed macular
edema and peripapillaryedema with epiretinal and intraretinal hemorrhages. The
optical coherence tomography, fluorescein angiography, as well as laboratory
tests were performed in order to exclude uveitis. Due to the difficulties in the
diagnosis indocyanine green angiography was also performed. Based on clinical
symptoms and the findings of the additional diagnostic procedures, the patient
was diagnosed with idiopathic choroidal neovascularization. The patient was
qualified for anti-VEGF therapy and received three intravitreal injections of
bevacizumab at the dose of 1.25 mg, at monthly intervals. RESULTS: Significant
improvement of visual acuity (VA RE - 1.0) and regression of the peripapillary
edema with hemorrhages were achieved after the third injection of 1.25 mg
bevacizumab. At 6 months, peripapillary scarring was observed in the area
involved by the primary lesions. CONCLUSIONS: Anti-VEGF therapy is the effective
treatment of idiopathic choroidal neovascularization in the described case. The
visual acuity improvement and rapid regression of posterior segment lesions after
bevacizumab administration were observed.
PMID- 25137921
TI - [Glaucoma after laser diode treatment in retinopathy of prematurity--case
series].
AB - The aim of this study was to analyze treatment and outcomes in children with
glaucoma secondary to diode laser photocoagulation in retinopathy of prematurity.
METHODS: The group of 1507 newborns, examined as outpatients between 2008 and
2013, were retrospectively analyzed. Five patients (0.3%) (nine eyes) with
glaucoma following laser treatment for retinopathy of prematurity were
identified. Demographic and clinical data was obtained from medical records and
compared with corresponding results in the group of glaucoma-free children
subjected to diode laser photocoagulation for retinopathy of prematurity. The
statistical analysis included Shapiro-Wilk test and U-Mann-Whitney test with
statistical significance level p < 0.05. RESULTS: The following data was
collected - mean post-menstrual age at the moment of photocoagulationwas 42 Hbd
(38-42) and it was 49.9 (43-54) weeks at the moment of diagnosis of angle-closure
glaucoma. The intraocular pressure was significantly elevated in nine in ten eyes
which was confirmed objectively and the mean intraocular pressure was 32.0 mmHg
(21.6-42.4). The mean corneal diameter was 11.25 mm (10-13) and it was associated
with the decreased corneal thickness in pachymetry (p < 0.05). Six eyes (66.6%)
required surgical intervention and intraocular pressure normalization was
achieved in all patients. Additionally, the affected eyes tended to be myopic
(mean spherical equivalent -1.625 diopter) and have a greater axial length (p <
0.05). CONCLUSIONS: Secondary glaucoma can develop following laser treatment for
severe retinopathy of prematurity. Topical treatment and surgical intervention
provide effective management.
PMID- 25137922
TI - [A case of familial pupillary iris pigment epithelium cysts].
AB - Iris cysts are rare lesions. In some cases, they may mimic melanoma and cause
diagnostic difficulties. Through imaging tests such as ultrasound biomicroscopy
we can evaluate the structure changes and determine the location for easy
diagnosis. Iris cysts often require only observation. In some cases specialist
treatment is necessary. One of the methods is transpupillary cystotomy perform
using the Nd:YAG laser. The paper presents the case of familial pupillary cysts
of the iris pigment epithelium in a father and a daughter.
PMID- 25137923
TI - Is binocular vision worth considering in people with low vision?
AB - In someone with good vision, binocular vision provides benefits which could not
be obtained by monocular viewing only. People with visual impairment often have
abnormal binocularity. However, they often use both eyes simultaneously in their
everyday activities. Much remains to be known about binocular vision in people
with visual impairment. As the binocular status of people with low vision
strongly influences their treatment and rehabilitation, it should be evaluated
and considered before diagnosis and further recommendations.
PMID- 25137924
TI - [Not only optic neuropathy: new molecular and clinical aspects of OPA1 gene
mutations].
AB - Autosomal dominant optic nerve atrophy is the most frequent dominantly inherited
optic neuropathy. The main causesof the disease are OPA1 gene mutations, which
are detected in about 60% of patients. Encoded by the nuclear genome the OPA1
protein plays an important role in a wide variety of processes crucial to the
proper functioning of mitochondria, the role of OPAl in many of them has been
discovered recently. A detailed study of patients with mutations in the OPA1 gene
has shown that about 20% of them present symptoms of a multiple system disease,
which may include hearing loss, progressive external ophthalmoplegia, ataxia,
myopathy, peripheral neuropathy, spastic paraparesis and multiple sclerosis-like
illness. This clinical manifestation is difficult to differentiate from other
neurodegenerative diseases, that is why genetic testing is very important in
order to determine the molecular basis of the disease in these patients.
PMID- 25137925
TI - [Terson syndrome--a literature review].
AB - Tersone syndrome was first described in 1900 as haemorrhages in the eye that
occur as a consequence of intracranial hemorrhage. The main cause of the syndrome
in adults is a subarachnoid hemorrhage following the rupture of intracranial
aneurysm. The pathogenesis has not been fully understood. It is believed that the
increase of intracranial pressure results in the hemodynamic changes in ocular
vessels. Reported symptoms include decrease of visual acuity following
generalized symptoms such as headache, loss of consciousness and meningealsigns.
Physical examination usually reveals vitreous hemorrhage (classic Terson's
syndrome) and other forms of intraocular hemorrhage. The authors reviewed the
available literature on the Terson's Syndrome. Clinical presentation,
pathogenesis, diagnosis, and available treatment options are presented and
discussed, considering the rare occurrence of this disease.
PMID- 25137926
TI - [Congenital optic disc anomalies--own observations].
AB - The aim of this article is to present a clinical picture of congenital optic
nerve anomalies, which occur quite frequently in the general population, may
cause low vision and visual field defects. These abnormalities can coexist with
central nervous system defects or the other ocular abnormalities. Some of them
may be misdiagnosed as papilloedema during the episode of intracranial fluid
pressure elevation or glaucomatous neuropathy. Diagnosing the congenital nerve
optic disc defects coexisting with multiorgans anomalies requires
multidisciplinary medical care especially in babies. developmental optic disc
anomalies, congenital eye abnormalities, differential diagnosis.
PMID- 25137927
TI - [Lucian Rydel (1833-1895)--ophthalmologist and the rector of the Jagiellonian
University of Cracow].
AB - Lucjan Rydel (1833-1895), was a Polish ophthalmologist, professor and the head of
the Department of Ophthalmology in Cracow, Dean of the Faculty of Medicine (1875
1878 and 1882-1883), the rector of the Jagiellonian University (1884-1888). He
studied medicine at the Jagiellonian University and the University of Vienna,
where he received the title of Doctor of Medicine in 1859, and Doctor of Surgery
in 1861. He was an assistant of F. Arlt. He had four sons: Adam (neurologist),
Lucjan (poet), Mieczyslaw, Stanislaw, and two daughters: Helena and Anna. His son
Lucjan (1870-1918) was a poet and a playwright of the Young Poland movement, a
journalist, a critic, a social activist and a pedagogue. He was a friend of
Stanistlaw Wyspianski. Lucjan Rydel was an author of dozens of clinical and
research works published in Polish and German. In his works, he described the
diagnosis and treatment of cataracts, corneal diseases, retinal degeneration,
retinal detachment and myopia. His article published in 1864 was one of the first
comprehensive works in Polish literature devoted to retinitis pigmentosa.
PMID- 25137928
TI - "Employers must back speaking out safely drive".
PMID- 25137929
TI - NICE sets out stall on staffing.
PMID- 25137930
TI - Lack of nurses at the top leads NMC to set up advisory panel.
PMID- 25137931
TI - Nurses "more cautious" than doctors in prescribing.
PMID- 25137933
TI - NICE: SIDS linked to sleeping with baby.
PMID- 25137932
TI - Training scheme cuts dementia drug use.
PMID- 25137934
TI - Preterm survival better in larger units.
PMID- 25137935
TI - Resist demands for antibiotics, staff told.
PMID- 25137936
TI - Nurses support prostate cancer drug appeal.
PMID- 25137937
TI - Nurses in Wales to get pound 160 but ministers reject blanket 1% pay rise.
PMID- 25137938
TI - End-of-life nursing care getting better.
PMID- 25137939
TI - Duty of candour for NHS closer to becoming law.
PMID- 25137940
TI - RCN ends indemnity insurance cover for employed members.
PMID- 25137941
TI - WW1 nurse to be celebrated with Royal Mint coin.
PMID- 25137942
TI - "Unison says yes to strike action and knows it can be done safely".
PMID- 25137943
TI - "Helping care home residents is not always in their interests".
PMID- 25137944
TI - Sobering thoughts about liver disease.
PMID- 25137946
TI - Overweight and obese adults: lifestyle weight management.
PMID- 25137945
TI - Comparing nurses' and doctors' prescribing habits.
AB - BACKGROUND: Nurses' prescribing activity in a mental health trust prompted
examination of whether nurse prescribers replicate their mentors' prescribing
habits. AIM: To explore nurses' and medical mentors' prescribing habits to inform
nurse-prescribing strategy. METHOD: The trust's 14 most-active nurse prescribers
and nine of their medical mentors were interviewed. Transcripts underwent
phenomenological analysis. RESULTS: 64 themes emerged showing nurses and doctors
approach prescribing differently. Themes were grouped into four categories.
DISCUSSION: Nurse prescribers tend to have greater holistic awareness of patients
but are also more risk averse. CONCLUSION: Greater strategic vision is required
to incentivise nurse prescribing; on its current trajectory it will not meet
identified prescribing needs.
PMID- 25137947
TI - Nursing care for end-stage liver disease.
AB - Nurses are seeing more and more patients with liver disease, many of whom are
under 65. Most common causes are avoidable and, as liver disease may take up to
30 years to develop, identifying those at risk is key. Patients with liver
disease often have a fluctuating course of complications that needs a team
approach to care. Improving end-of-life care can also reduce the number of these
patients who die in hospital. This article, the first in a two-part series,
explores some common complications of liver disease and best practice for nurses
treating patients with end-stage liver disease.
PMID- 25137948
TI - A toolkit for encouraging activities in care homes.
AB - Activity is vital for the physical and psychological wellbeing of care home
residents. It should be an integral part of their daily routine but can be viewed
as an additional burden for busy staff. Activity is defined as everything we
"do", and even older people who are frail can still be active. Nurses need to
consider how activity can be incorporated into residents' daily lives; the Living
Well Through Activity in Care Homes toolkit, produced by the College of
Occupational Therapists, aims to help staff provide meaningful activities for
residents.
PMID- 25137949
TI - Reducing need to restrain vulnerable patients.
AB - A multiprofessional consortium led by the Royal College of Nursing has developed
guidance on reducing the need for restrictive interventions in hospitals and
residential or care homes. The guidance, published by the Department of Health
this year, states that nurses and other staff must create therapeutic
environments that promote wellness, and must use restrictive interventions only
when there is a real possibility of harm to the person, staff or the public.
Staff must not restrain people in a way that affects their airway, breathing or
circulation, and restrictive intervention must not include the deliberate
application of pain. Interventions used must always be the least restrictive
option to meet the immediate need.
PMID- 25137950
TI - 60 seconds with Garry Swann.
PMID- 25137951
TI - Driving down cases of TB.
PMID- 25137952
TI - [Healthy aging].
PMID- 25137953
TI - [Genevieve Ruault, homage to a grand lady].
PMID- 25137954
TI - [Cerebrovascular accidents, don't forget number 15].
PMID- 25137955
TI - [The benefits of home health aides].
PMID- 25137956
TI - [Decision making, medical treatment and the end of life].
PMID- 25137957
TI - [Preventing psychological suffering and suicide in the elderly].
PMID- 25137958
TI - [A simple tool to measure the immediate wellbeing of elderly people in nursing
homes].
AB - Immediate wellbeing and quality of life in an institution are of paramount
importance. The assessment of the quality of life of elderly people is both
complex and poorly adapted to daily practices. The instant assessment of
wellbeing tool (EVIBE), developed in the field, is an original and practical
alternative. This tool allows caregivers to carry out an immediate assessment and
a qualitative approach with residents while involving professionals in a well
treatment approach improving daily practices.
PMID- 25137959
TI - [Speech therapy for cognitive disorders in elderly patients].
AB - The aim of providing speech therapy to elderly patients, in the framework of a
personalised approach, is to help them maintain their autonomy and delay their
move to a specialised hospital. The family and caregivers play an essential role
in ensuring the success of this therapy.
PMID- 25137960
TI - [Interprofessionalism in geriatrics].
AB - A system for the coordinated care of elderly people in geriatrics was set up at
Luxembourg general hospital. The creation of the short-stay geriatric unit
resulted in a reorganisation which questioned the notions of team, cohesion and
skill. This article describes the successful experience and the benefit it has
brought patients.
PMID- 25137961
TI - [Non pharmacological management of cognition disorders. Listening and calming
tensions].
PMID- 25137962
TI - [Non pharmacological therapies for Alzheimer's].
AB - A number of non pharmacological therapies for Alzheimer's disease exist, focusing
on cognitive, psycho-social, sensory, physical and environmental aspects.
Although their absolute efficacy has not been proven, their results are
encouraging. Outpatient therapy to maintain patients' competencies changes how
the objectives and methods of patient care are viewed. By establishing
individualised, relational care, it aims above all to preserve the patient's
quality of life. It recognises the role, contribution and skill of the caregiver.
PMID- 25137964
TI - [Nursing care and essential oils in geriatrics].
AB - Aromatherapy is a valuable complementary therapeutic tool which is increasingly
being used in hospitals. Essential oils help to improve patients' quality of
life. They can be used for well-being purposes as well in specific nursing
procedures. Some services offer aromatherapy through diffusion, inhalation,
massages or aromatic baths. The benefits for healthcare teams as well as for
patients are undeniable. There is also a significant reduction in the consumption
of certain drugs.
PMID- 25137963
TI - [The snoezelen as a form of caring].
AB - The concept of the snoezelen originated in The Netherlands. It is based on the
stimulation of the senses and relaxation. It offers a unique opportunity for
human contact between the caregiver and the patient, which helps to restore self
awareness and improve the distorted body percept. It emphasises the caring aspect
of nursing.
PMID- 25137965
TI - [Haptonomy in geriatric units].
AB - Haptonomy lies at the heart of the human relationship. This specific contact
concerns the most sensitive part of the human being and considers the person as a
whole. The indications are notably the feeling of abandonment or insecurity.
Testimony.
PMID- 25137966
TI - [The therapeutic meal, a moment of sharing].
AB - Therapeutic meals were set up at Chateau-Gombert geriatric clinic in Marseille on
the initiative of the hospital's dietician and psychologist. They are an
opportunity for elderly people who may or may not have cognitive disorders and
who are suffering from eating disorders to enjoy and share in a convivial moment
and to rediscover a sometimes forgotten ritual. The initiative has had a positive
effect on the quantity of food eaten.
PMID- 25137968
TI - [A storyteller in gerontology].
AB - Storytelling in geriatrics is a way of contributing to the construction of an
alternative to the pharmacological treatment of cognitive disorders. To carry out
such an activity, aside from having a repertoire of targeted stories and the
talent of a good storyteller, it is important to know how to create a convivial
atmosphere where the patient will feel appreciated and valued.
PMID- 25137967
TI - [A garden as a care tool in a cognitive-behavior unit].
AB - Cognitive-behaviour units are specialised units within follow-up and
rehabilitation care services for people suffering from Alzheimer's disease. These
units were created in response to measure 17 of the 3rd Alzheimer's Plan. To
stabilise behavioural disorders, as part of a non pharmacological care plan, the
therapeutic garden is a useful care tool. This article presents an original
initiative in Nancy.
PMID- 25137969
TI - [Bibliography. Non pharmacological management of cognition disorders].
PMID- 25137970
TI - [Never neglect the medical history of a patient].
PMID- 25137971
TI - [Prevention of inappropriate prescriptions in the elderly].
PMID- 25137972
TI - Safe and sound. Informed design approaches help to prevent patient harm.
PMID- 25137973
TI - A new utility.
PMID- 25137974
TI - Data-driven planning. Statistical research an Lean concepts help determine space
needs.
PMID- 25137975
TI - Measuring up. Strategies for benchmarking cooling water systems.
PMID- 25137976
TI - Built to last. Furniture designers push the envelope on durability, comfort and
ergonomics.
PMID- 25137977
TI - Surface safety. Best practices in surface and medical device disinfection.
PMID- 25137978
TI - Adapting to the new health care environment.
PMID- 25137979
TI - Applying Lean principles to ES operations.
PMID- 25137980
TI - A deciding role. ES involvement in the design and construction process.
PMID- 25137981
TI - ["I am mostly interested in special, seemingly unsolvable problems related to
surgery" Conversation with Dr. Gabor Vogt].
PMID- 25137982
TI - [Once more on the heart cathedral--paradogmas for the heart as a symbol].
PMID- 25137983
TI - [The artist and his age].
PMID- 25137984
TI - [The Helsinki Declaration at 50 years: comments on the 2013 modifications].
PMID- 25137985
TI - [A professor of ophthalmology at the University of Harkov].
PMID- 25137986
TI - Cross-border collaboration.
PMID- 25137987
TI - Cure for the common clinic.
PMID- 25137988
TI - A standard of care: patient-safety advocates issue call for watchdog.
PMID- 25137989
TI - HHS defends expanded 340B drug discounts.
PMID- 25137990
TI - States struggle to find sources to fund Obamacare exchanges for 2015.
PMID- 25137991
TI - Diagnosing a community's health needs. Not-for-profit hospitals target health
improvement efforts under reform law.
PMID- 25137992
TI - The flaw in the law. Millions at risk of losing coverage in lawsuit challenging
subsidies.
PMID- 25137993
TI - Better reporting--the next step in reducing patient harm.
PMID- 25137994
TI - Healthcare leaders must live in today's world and plan for tomorrow's.
PMID- 25137995
TI - Committed to publicly reporting both the good and the bad.
PMID- 25137996
TI - Hospital margins slump due to squeeze from volume, rates, investments.
PMID- 25137997
TI - Smarter checklists. Designers of comprehensive app hope to advance hospital use
of patient-safety tools.
PMID- 25137998
TI - The big bulk up. Hospital systems grow through dealmaking as regulators fret
about prices.
PMID- 25137999
TI - Efficient, quality care can aid shrinking margins.
PMID- 25138000
TI - Acquisitions and affiliations: how the new wave is different.
PMID- 25138001
TI - Maine hospital slashes transfusions, reducing patient risk, costs.
PMID- 25138002
TI - Think more about how technology affects quality.
PMID- 25138003
TI - Don't blame fat.
PMID- 25138004
TI - The changing lives of teens. Kids have cut some risky behaviors--and picked up
others.
PMID- 25138005
TI - Dieters, beware. Supplements for weight loss are heavy on claims and light on
scientific proof.
PMID- 25138006
TI - The contraception showdown.
PMID- 25138007
TI - Applications of induced pluripotent stem cells in the modeling of human
inflammatory bowel diseases.
AB - Inflammatory bowel diseases (IBDs) are chronic and involve the gastrointestinal
tract; the two primary IBDs are ulcerative colitis and Crohn's disease. Existing
treatments for IBD include control of active inflammation and regulation of
immune disorders, and commonly used drugs include salicylates, corticosteroids,
and immunosuppressants. At the same time, an in-depth study of IBD pathogenesis
promoted the acceptance of bioimmunotherapy by increasing numbers of people.
However, long-term use of these drugs can cause adverse reactions that are
difficult for patients to overcome, with limited efficacy for critically ill
patients. Recent studies have found that stem cell transplantation is a new and
effective therapy and IBD treatment, particularly for refractory cases. Stem
cells, especially induced pluripotent stem cells (iPSCs), can differentiate into
functional intestinal epithelia and their use avoids ethical issues arising from
embryonic stem cells, providing a new kind of seed cell for alternative
treatments for IBD. This paper reviews iPSCs as a potential new treatment for
IBDs in order to provide an experimental and clinical reference.
PMID- 25138008
TI - The composition of WHO's expert committee on essential medicines needs more
scrutiny.
PMID- 25138009
TI - Egg-yolk protein by-product as a source of ACE-inhibitory peptides obtained with
using unconventional proteinase from Asian pumpkin (Cucurbita ficifolia).
AB - In the present study angiotensin I-converting enzyme (ACE) inhibitory peptides
were isolated from egg-yolk protein preparation (YP). Enzymatic hydrolysis
conducted using unconventional enzyme from Cucurbita ficifolia (dose: 1000 U/mg
of hydrolyzed YP (E/S (w/w)=1:7.52)) was employed to obtain protein hydrolysates.
The 4-h hydrolysate exhibited a significant (IC50=482.5 MUg/mL) ACE inhibitory
activity. Moreover, hydrolysate showed no cytotoxic activity on human and animal
cell lines which makes it a very useful multifunctional method for peptide
preparation. The compiled isolation procedure (ultrafiltration, size-exclusion
chromatography and RP-HPLC) of bioactive peptides from YP hydrolysate resulted in
obtaining peptides with the strong ACE inhibitory activity. One homogeneous and
three heterogeneous peptide fractions were identified. The peptides were composed
of 9-18 amino-acid residues, including mainly arginine and leucine at the N
terminal positions. To confirm the selected bioactive peptide sequences their
analogs were chemically synthesized and tested. Peptide LAPSLPGKPKPD showed the
strongest ACE inhibitory activity, with IC50 value of 1.97 MUmol/L. BIOLOGICAL
SIGNIFICANCE: Peptides with specific biological activity can be used in
pharmaceutical, cosmetic or food industries. Because of their potential role as
physiological modulators, as well as theirhigh safety profile, they can be used
as natural pharmacological compounds or functional food ingredients. The
development of biotechnological solutions to obtain peptides with desired
biological activity is already in progress. Studies in this area are focused on
using unconventional highly specific enzymes and more efficient methods developed
to conduct food process technologies. Natural peptides have many advantages. They
are mainly toxicologically safe, have wide spectra of therapeutic actions,
exhibit less side effects compared to synthetic drugs and are more efficiently
absorbed in the intestinal tract. The complexity of operation of large scale
technologies and high cost of purification techniques are limiting factors to the
commercialization of food-derived bioactive peptides. Research on the isolation
of bioactive peptides in order to reduce the processing time and costs is
continuously developing. Bioactive peptides can also be released from protein by
products of the food industry, which reduce the substrate expense and production
cost as well as provide the added advantage of an efficient waste disposal.
Moreover, proteins as precursors of food-derived peptides are well-tolerated by
the human body and therefore their application in drug development may reduce
costs and duration of toxicological studies during research, development and
clinical trials.
PMID- 25138012
TI - Cross-national comparison of job satisfaction in doctors during economic
recession.
AB - BACKGROUND: Job satisfaction in doctors is related to migration, burnout,
turnover and health service quality. However, little is known about their job
satisfaction during economic recessions. Iceland and Norway have similar health
care systems, but only Iceland was affected severely by the 2008 economic crisis.
AIMS: To examine job satisfaction in Icelandic and Norwegian doctors, to compare
job satisfaction with Icelandic data obtained before the current recession and to
examine job satisfaction in response to cost-containment initiatives. METHODS: A
survey of all doctors working in Iceland during 2010, a representative comparison
sample of Norwegian doctors from 2010 and a historic sample of doctors who worked
at Landspitali University Hospital in Iceland during 2003. The main outcome
measure was job satisfaction, which was measured using a validated 10-item scale.
RESULTS: Job satisfaction levels in Icelandic doctors (response rate of 61%, n =
622/1024), mean = 47.7 (SD = 10.9), were significantly lower than those of
Norwegian doctors (response rate of 67%, n = 1025/1522), mean = 53.2 (SD = 8.5),
after controlling for individual and work-related factors. Doctors at Landspitali
University Hospital (response rate of 59%, n = 345/581) were less satisfied
during the recession. Multiple regression analysis showed that cost-containment
significantly affected job satisfaction (P < 0.001). CONCLUSIONS: Job
satisfaction in doctors was lower in Iceland than in Norway, which may have been
attributable partly to the current economic recession.
PMID- 25138013
TI - The prevalence of respiratory symptoms among mushroom workers in Ireland.
AB - BACKGROUND: Respiratory conditions such as asthma, bronchitis, hypersensitivity
pneumonitis and upper airways symptoms have been ascribed to fungal exposures.
Mushroom workers may be at risk of these as a consequence. AIMS: To assess the
prevalence of respiratory symptoms in mushroom workers. METHODS: A cross
sectional study assessed 4 weeks of respiratory symptoms among mushroom workers
divided into four categories of exposure, using a self-administered respiratory
questionnaire and spirometry. RESULTS: The population of 191 subjects was
predominantly (66%) from Eastern Europe; 61% were women and 39% were under 30. It
included 73 growers, 38 composters, 26 administrators and 52 packers. Among all
workers, there was a high prevalence (67%) of one or more respiratory symptoms
which did not appear to vary by age, gender, pack-years of smoking or duration of
employment. There was a significant improvement in respiratory symptoms in
workers during absence from the workplace (P < 0.001). Spirometry readings across
all groups were within normal values. Symptom profiles suggest that as many as 22
workers had symptoms of airways disease; 18 (82%) of these were mushroom growers.
Growers were significantly more likely to have symptoms consistent with airways
disease than all other workers, odds ratio 9.2 (95% CI 3.0-28.4). CONCLUSIONS:
There was a high prevalence of respiratory symptoms among mushroom workers.
Mushroom growers may be at high risk of airways disease, possibly from fungal
antigens or related exposures.
PMID- 25138014
TI - An overview of the sequence features of N- and C-terminal segments of the human
chemokine receptors.
AB - Chemokine receptors play a crucial role in the cellular signaling enrolling
extracellular ligands chemotactic proteins which recruit immune cells. They
possess seven trans-membrane helices, an extracellular N-terminal region with
three extracellular hydrophilic loops being important for search and recognition
of specific ligand(s), and an intracellular C-terminal region with three
intracellular loops that couple G-proteins. Although the functional aspects of
the terminal segments of the extra-and intra-cellular G proteins are universally
identified, the molecular basis on which they rest are still unclear because they
are not definable by means of X-rays due to their high mobility and are not easy
to study in the membrane. The purpose of this work is to define which physical
chemical properties of the terminal segments of the human chemokine receptors are
at the basis of their functional mechanisms. Therefore, we have evaluated their
physical-chemical properties in terms of amino acid composition, local
flexibility, disorder propensity, net charge distribution and putative sites of
post-translational modifications. Our results support the conclusion that all 19
C-terminal and N-terminal segments of human chemokine receptors are very flexible
due to the systematic presence of intrinsic disorder. Although, the purpose of
this plasticity clearly appears that of controlling and modulating the binding of
ligands, we provide evidence that the overlap of linearly charged stretches,
intrinsic disorder and post-translational modification sites, consistently found
in these motives, is a necessary feature to exert the function. The role of the
intrinsic disorder has been discussed considering the structural information
coming from intrinsically disordered model compounds which support the view that
the chemokine terminals have to be considered as strong polyampholytes or
polyelectrolytes where conformational ensembles and structural transitions
between them are modulated by charge fraction variations. Also the role of post
translational modifications has been found coherent with this view because,
changing the charge fraction, they guide structural transitions between
ensembles. Moreover, we have also considered our results from an evolutionary
point of view in order to understand if the features found in humans were also
present in other species. Our data evidenced that the structural features of the
human terminals of the chemokine receptors were shared and evolutionarily
conserved particularly among mammals. This means that the various organisms not
only tolerate but select intrinsic disorder for the terminal regions of their
receptors, reflecting constraints that point to molecular recognition. In
conclusion the terminal segments of chemokine receptors must be considered as
strong polyampholytes where the charge fraction variations induced by post
translational modifications are the driving physico-chemical feature able to
adapt the conformations of the terminal segments to their functions.
PMID- 25138015
TI - Development of a cytokine-producing immortalized murine Kupffer cell line.
AB - Kupffer cells (KC) play a critical role in both liver physiology and the
pathogenesis of various liver diseases. Isolated primary KC have a limited
lifespan in culture, and due to the relatively low number obtained, limit their
study in vitro. Here, a cytokine-producing immortalized KC (ImKC) line was
established from transgenic mice that express the thermolabile mutant tsA58 of
the Simian virus 40 large T antigen under the control of the H-2k(b) promoter.
Primary KC were obtained using a three step procedure: liver perfusion,
centrifugal elutriation, and sorting for F4/80+ cells. ImKC were identified
within the small-intermediate population of KC that maintained stable expression
of F4/80, and the surface antigens CD11b, CD14 and TLR4. ImKC grow at IFNgamma
independent manner at 37 degrees C and exhibited a doubling time of ~24 h when
cultured in RPMI 1640 with 5% FBS. Our observations indicate that both activation
of telomerase and expression of P53 are markedly increased, suggesting that
enhanced telomerase activity and P53 expression may contribute to the
immortalization of this cell population. ImKC cells maintained a high capacity to
phagocytose FITC-latex beads, and bind/phagocytose erythrocytes. In addition,
similar to primary KC, ImKC responded to stimulation with lipopolysaccharide
(LPS: 0.1-1MUg/ml) by upregulating mRNA levels of TNFalpha (23-fold), IL-6 (28
fold), and IL-1beta (1459-fold), as measured by qRT-PCR. Protein levels of
TNFalpha and IL-6 were also increased, 10-fold and 12-fold, respectively.
Reactive oxygen species (ROS) and nitric oxide (NO) production were significantly
enhanced in ImKC following an LPS challenge. Furthermore, LPS elicited a marked
increase in mitogen activated protein kinase (MAPK) phospho-(ERK1/2, JNK) and NF
kappaB p50 with decreased IkappaBalpha in ImKC, as assessed by Western blot.
Collectively, these results demonstrate that the ImKC line retains critical
characteristics of primary KC, and thus provides a useful tool to assess the role
of KC in liver injury and chronic diseases.
PMID- 25138016
TI - Serum cytokine profiles of Khorasan veterans 23 years after sulfur mustard
exposure.
AB - Sulfur mustard (SM) is an incapacitating chemical warfare agent that was used
against Iranian soldiers during the period from 1983 to 1988. We have
investigated serum cytokines profiles of Khorasan veterans who were exposed to SM
>23 years earlier. Forty-four male Iranian veterans who had >40% disabilities due
to delayed complications of SM poisoning and had disabilities were investigated.
A total of 30 healthy male volunteers (relatives of the veterans) were selected
as the control group. Cytokine levels were measured in the serum of case and
control subjects using commercial ELISA kits. Hematologic parameters (white/red
blood cell counts, hemoglobin levels, immune cell differentials) were also
performed on blood samples from the study subjects. The results indicated that
serum levels of ICAM-1 were significantly higher in the samples from SM-exposed
veterans (772.8 [+/- 15.1] ng/ml [p=0.014] vs. control values of 710.2 [+/- 20.0]
ng/ml). On the other hand, serum IL-1beta, IL-8 levels and TNFalpha, were
significantly lower for the veterans than the controls (IL-1beta: 3.8 [+/- 0.1]
vs. 4.3 [+/- 0.2] pg/ml, p=0.037; IL-8: 21.0 [+/- 6.1] vs. 84.6 [+/- 20.3] pg/ml,
p=0.002; TNFalpha: 4.5 [+/- 0.1] vs. 5.5 [+/- 0.1] pg/ml, p=0.027). Levels of
other assayed cytokines, e.g., IL-2, -4, -5, -6, -10, and -12, IFNgamma, TNFbeta,
and sVCAM-1 were not significantly different between the study populations. None
of the assayed hematologic parameters appeared to differ as well. It seems
possible that dysfunctions could have been induced in the innate immune functions
of the SM-exposed veterans as a result of these changes in cytokine expression
and that these, in turn, may have contributed to the increased incidence of a
myriad of diseases that have been documented in these veterans, including
cancers. Future studies must focus on examining the significance of these changes
in circulating cytokines and their potential contribution to the development of
different diseases in veterans exposed to SM.
PMID- 25138017
TI - Interleukin-28A enhances autoimmune disease in a retinal autoimmunity model.
AB - Interleukin-28A (IL-28A), a member of type III interferons (IFN-lambdas),
promotes antiviral, antitumor and immune responses. However, its ability to
regulate autoimmune diseases is poorly understood. In this study, we examined the
effect of IL-28A on retinal antigen-induced experimental autoimmune uveoretinitis
(EAU), a mouse model of human T-cell-mediated autoimmune eye disease. We found
that administration of IL-28A enhanced EAU scores and autoimmune response
parameters including delayed-type hypersensitivity (DTH), Ag-specific T cell
proliferation and the production of Ag-specific IL-17 and IFN-gamma in the
priming phase. The effect of IL-28A was abrogated by administration of a
neutralizing antibody against IL-28A. Our results suggest that IL-28A is capable
of exacerbating a T-cell-mediated autoimmune disease. Thus, targeting IL-28A may
provide a new therapeutic approach to T cell-mediated autoimmune diseases such as
uveitis.
PMID- 25138018
TI - Bone marrow involvement of Langerhans cell histiocytosis: immunohistochemical
evaluation of bone marrow for CD1a, Langerin, and S100 expression.
AB - AIMS: Although bone marrow (BM) involvement in Langerhans cell histiocytosis
(LCH) is a negative prognostic indicator, there are no widely accepted criteria
to define BM involvement in LCH. We evaluated the BM of LCH patients at diagnosis
by immunohistochemical (IHC) staining for S100, CD1a and Langerin, along with
other features. METHODS AND RESULTS: We retrospectively reviewed the records of
75 patients diagnosed as LCH at our center. IHC stains of Langerin, CD1a and S100
were done using paraffin-embedded tissue sections. Only three cases showed
massive involvement of clustered Langerhans cells. There were linear associations
between positive cell count and disease extent. Some discordant results between
Langerin and CD1a IHC stains were noted. Among cases showing positive results for
all three IHC stains, six patients (54.5%) were in the multisystem group, and
three patients (27.3%) had cytopenias. The reactivation-free survival rates did
not differ between the group positive for CD1a or Langerin, and the group
negative for Langerin and CD1a. CONCLUSIONS: Langerin and CD1a seem to be useful
markers of Langerhans cells, and S100 might be a nonspecific marker for these
cells, in the BM. Both Langerin and CD1a IHC staining is needed to evaluate the
BM involvement of LCH.
PMID- 25138019
TI - An online version of the Mooney Face Test: phenotypic and genetic associations.
AB - The Mooney Face Test is a widely used test of face perception, but was originally
designed to be administered by personal interview. We have developed a three
alternative forced-choice version for online testing. We tested 397 healthy
adults between the ages of 18 and 42 (M=24 years). There was a wide range of
performance (64-100% correct; M=89.6%). We observed a significant sex difference
favoring males (.31 standard deviation; p =.004). In addition, independently of
sex, higher 2D:4D digit ratios were significantly associated with higher scores
(rho=.14, p=.006). A genome-wide association study (GWAS) for a subset of 370
participants identified an association between Mooney performance and a
polymorphism in the RAPGEF5 gene (rs1522280; p=9.68*10(-8)). This association
survives a permutation test (p=.031).
PMID- 25138020
TI - Repeating pulmonary rehabilitation: prevalence, predictors and outcomes.
AB - BACKGROUND AND OBJECTIVE: Pulmonary rehabilitation (PR) is a cornerstone of care
in chronic respiratory diseases; yet its benefits diminish over time. Repeating
PR may be beneficial; however, little is known about the characteristics and
outcomes of repeaters. This study aimed to establish the proportion of repeaters,
identify characteristics that predict repetition and compare the magnitude of
benefits achieved between initial and subsequent programmes. METHODS: Patients
with stable chronic respiratory diseases who attended PR over a 9-year period
were included. Outcome measures included the 6-min walk distance (6MWD) and the
Chronic Respiratory Disease Questionnaire-Self-Reported (CRDQ-SR). Independent
predictors of repeating were identified. RESULTS: Of 296 patients, 59 (20%)
repeated PR, most within 1-3 years. Following the initial programme, repeaters
had significant decline in 6MWD (-96.1 +/- 84.6 m; P < 0.001) and CRDQ-SR scores
(mean decline -3.6 points, range -0.1 to -7.9 points; P < 0.005). The improvement
in 6MWD was less in the repeat programme compared with the first (38.4 +/- 50.7 m
vs 67 +/- 40.4 m; P = 0.005), while the change in CRDQ-SR was similar in all
domains. A chronic obstructive pulmonary disease diagnosis increased the odds of
repeating PR (odds ratio (OR) 4.8; P = 0.005) while improved mastery in the
initial programme reduced the odds (OR 0.9; P = 0.033). CONCLUSIONS: One in five
patients repeated PR, achieving clinically significant improvements in exercise
tolerance and quality of life. Patients with small improvements in disease
mastery after initial PR were more likely to repeat the programme and may benefit
from earlier intervention or longer duration PR.
PMID- 25138022
TI - Coadministrating luteolin minimizes the side effects of the aromatase inhibitor
letrozole.
AB - Aromatase inhibitors (AIs) have been used as adjuvant therapeutic agents for
breast cancer. Their adverse side effect on blood lipid is well documented. Some
natural compounds have been shown to be potential AIs. In the present study, we
compared the efficacy of the flavonoid luteolin to the clinically approved AI
letrozole (Femara; Novartis Pharmaceuticals, East Hanover, NJ) in a cell and a
mouse model. In the in vitro experimental results for aromatase inhibition, the
Ki values of luteolin and letrozole were estimated to be 2.44 uM and 0.41 nM,
respectively. Both letrozole and luteolin appeared to be competitive inhibitors.
Subsequently, an animal model was used for the comparison. Aromatase-expressing
MCF-7 cells were transplanted into ovariectomized athymic mice. Luteolin was
given by mouth at 5, 20, and 50 mg/kg, whereas letrozole was administered by
intravenous injection. Similar to letrozole, luteolin administration reduced
plasma estrogen concentrations and suppressed the xenograft proliferation. The
regulation of cell cycle and apoptotic proteins-such as a decrease in the
expression of Bcl-xL, cyclin-A/D1/E, CDK2/4, and increase in that of Bax-was
about the same in both treatments. The most significant disparity was on blood
lipids. In contrast to letrozole, luteolin increased fasting plasma high-density
lipoprotein concentrations and produced a desirable blood lipid profile. These
results suggested that the flavonoid could be a coadjuvant therapeutic agent
without impairing the action of AIs.
PMID- 25138023
TI - [Burnout among high school students and tobacco use].
PMID- 25138021
TI - Thrombin inhibition with dabigatran protects against high-fat diet-induced fatty
liver disease in mice.
AB - Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of obesity
and metabolic syndrome. Robust coagulation cascade activation is common in obese
patients with NAFLD. We identified a critical temporal relationship between
thrombin generation and the manifestation of hepatic steatosis, inflammation, and
injury in C57BL/6J mice fed a high-fat diet (HFD) for 1, 2, and 3 months. Mice
fed a HFD exhibited dramatic increases in hepatocellular injury and inflammation
over time. Hepatic fibrin deposition preceded an increase in serum alanine
aminotransferase, and the most dramatic changes in liver histopathology occurred
in conjunction with a detectable increase in plasma thrombin-antithrombin levels
at 3 months. To directly determine whether thrombin activity promotes NAFLD
pathogenesis, mice were fed a HFD and simultaneously treated with the direct
thrombin inhibitor dabigatran etexilate for 3 months. Notably, dabigatran
treatment significantly reduced hepatic fibrin deposition, hepatic inflammation,
hepatocellular injury, and steatosis in mice fed a HFD. Of interest, dabigatran
treatment also significantly attenuated HFD-induced body weight gain. Gene
expression analysis suggested that thrombin potentially drives NAFLD pathogenesis
by altering the expression of genes associated with lipid metabolism and bile
acid synthesis. Collectively, the results suggest that thrombin activity is
central to HFD-induced body weight gain, liver injury, and inflammation and
provide the proof-of-principle evidence that pharmacological thrombin inhibition
could be effective in limiting NAFLD and associated pathologies.
PMID- 25138024
TI - Urinary metabolomics for noninvasive detection of borderline and acute T cell
mediated rejection in children after kidney transplantation.
AB - The goal of this study was to evaluate the utility of urinary metabolomics for
noninvasive diagnosis of T cell-mediated rejection (TCMR) in pediatric kidney
transplant recipients. Urine samples (n = 277) from 57 patients with surveillance
or indication kidney biopsies were assayed for 134 unique metabolites by
quantitative mass spectrometry. Samples without TCMR (n = 183) were compared to
borderline tubulitis (n = 54) and TCMR (n = 30). Partial least squares
discriminant analysis identified distinct classifiers for TCMR (area under
receiver operating characteristic curve [AUC] = 0.892; 95% confidence interval
[CI] 0.827-0.957) and borderline tubulitis (AUC = 0.836; 95% CI 0.781-0.892),
respectively. Application of the TCMR classifier to borderline tubulitis samples
yielded a discriminant score (-0.47 +/- 0.33) mid-way between TCMR (-0.20 +/-
0.34) and No TCMR (-0.80 +/- 0.32) (p < 0.001 for all comparisons). Discriminant
scoring for combined borderline/TCMR versus No TCMR (AUC = 0.900; 95% CI 0.859
0.940) applied to a validation cohort robustly distinguished between samples with
(-0.08 +/- 0.52) and without (-0.65 +/- 0.54, p < 0.001) borderline/TCMR (p <
0.001). The TCMR discriminant score was driven by histological t-score, ct-score,
donor-specific antibody and biopsy indication, and was unaffected by renal
function, interstitial or microcirculatory inflammation, interstitial fibrosis or
pyuria. These preliminary findings suggest that urinary metabolomics is a
sensitive, specific and noninvasive tool for TCMR identification that is superior
to serum creatinine, with minimal confounding by other allograft injury
processes.
PMID- 25138025
TI - Inflammation and immune system activation after traumatic brain injury.
AB - Treatment options for managing traumatic brain injury remain limited. Therapies
that limit the development of secondary brain injury--the delayed injury that can
occur days to weeks after initial presentation--would have a major impact on
outcomes and reduce the medical, social, and economic burden of this devastating
disease. A growing body of evidence suggests that inflammation and activation of
the immune system is a central driver of secondary brain injury. This article
reviews the evidence for inflammation mediating secondary injury after head
trauma and outlines potential approaches for immunomodulatory therapies after
traumatic brain injury.
PMID- 25138028
TI - The challenge: do pharmaceuticals present a risk to the environment, and what
needs to be done to answer the question?
PMID- 25138027
TI - In response: industry perspective.
PMID- 25138026
TI - Endogenous retrovirus-K and nervous system diseases.
AB - A new appreciation of the microbiome is changing the way we perceive human health
and disease. The holobiontic nature of humans is even etched into our DNA in the
form of viral symbionts. Empirical evidence for the presence of endogenous
retroviruses (ERVs) in the human genome and their activity in homeostatic and
pathologic states has accumulated; however, no causal relationship with human
disease has been established to date. In this review, we will focus on the role
of endogenous retrovirus-K in neurologic disease. Specifically, we will attempt
to reconcile the pathologic contribution of ERVK in disparate neurologic diseases
by providing evidence as to inter-individual differences in ERVK genotypes,
addressing the molecular regulation of ERVK, and provide detailed examples of
ERVK-mediated processes in nervous system diseases.
PMID- 25138029
TI - In response: governmental perspective.
PMID- 25138030
TI - Thrombospondin-1 is produced by retinal glial cells and inhibits the growth of
vascular endothelial cells.
AB - BACKGROUND/AIMS: By the release of antiangiogenic factors, Muller glial cells
provide an angiostatic environment in the normal and ischemic retina. We
determined whether Muller cells produce thrombospondin-1 (TSP-1), a known
inhibitor of angiogenesis. METHODS: Secretion of TSP-1 by cultured Muller cells
was determined with ELISA. Slices of rat retinas and surgically excised retinal
membranes of human subjects were immunostained against TSP-1 and the glial marker
vimentin. The effects of TSP-1 on the growth of bovine retinal endothelial cells
(BRECs) and activation of ERK1/2 were determined with DNA synthesis and migration
assays, and Western blotting, respectively. RESULTS: Cultured Muller cells
secrete TSP-1 under normoxic and hypoxic (0.2% O2) conditions. Secretion of TSP-1
was increased in hypoxia compared to normoxia. In rat retinal slices, glial,
retinal ganglion, and possibly horizontal cells were stained for TSP-1. Retinal
glial cells in preretinal membranes from human subjects with nonhypoxic
epiretinal gliosis (macular pucker) and proliferative diabetic retinopathy,
respectively, were immunopositive for TSP-1. Exogenous TSP-1 reduced the VEGF
induced proliferation and migration of BRECs and decreased the phosphorylation
level of ERK1/2 in BRECs. CONCLUSION: The data suggest that Muller cells are one
major source of TSP-1 in the normal and ischemic retina. Glia-derived TSP1 may
inhibit angiogenic responses in the ischemic retina.
PMID- 25138031
TI - Lutecium fluoride hollow mesoporous spheres with enhanced up-conversion
luminescent bioimaging and light-triggered drug release by gold nanocrystals.
AB - Uniform Na5Lu9F32 hollow mesoporous spheres (HMSs) have been successfully
prepared by a facile and mild (50 degrees C for 5 h) coprecipitation process,
and Au nanocrystals (NCs) with particle size of about 10 nm were conjugated to
poly(ether imide) (PEI) modified HMSs by electrostatic interaction. Compared with
Na5Lu9F32:Yb/Er HMSs, the up-conversion (UC) luminescence intensity of
Na5Lu9F32:Yb/Er@Au HMSs was much higher under low pump power due to the local
field enhancement (LFE) of Au NCs, and there is a surface plasmon resonance (SPR)
effect with nonradiative transitions which generates a thermal effect. These two
effects have been proved by theoretical discrete-dipole approximation (DDA)
simulation. The good biocompatibility of Na5Lu9F32:Yb/Er@Au HMSs indicates them
as a promising candidate in the biological field. Particularly, under near
infrared (NIR) laser irradiation, a rapid doxorubicin (DOX) release was achieved
due to the thermal effect of Au NCs. In this case, Na5Lu9F32:Yb/Er@Au HMSs
exhibit an apparent NIR light-controlled "on/off" drug release pattern. In
addition, UC luminescent images uptaken by cells show brighter green and red
emission under NIR laser excitation. Therefore, this novel multifunctional
(mesoporous, enhanced UC luminescent, and light-triggered drug release) material
should be potential as a suitable targeted cancer therapy carrier and bioimaging.
PMID- 25138034
TI - Coronary artery tortuosity in spontaneous coronary artery dissection:
angiographic characteristics and clinical implications.
AB - BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly
recognized nonatherosclerotic cause of acute coronary syndrome. The angiographic
characteristics of SCAD are largely undetermined. The goal of this study was to
determine the prevalence of coronary tortuosity in SCAD and whether it may be
implicated in the disease. METHODS AND RESULTS: Patients with confirmed SCAD
(n=246; 45.3+/-8.9 years; 96% women) and 313 control patients without SCAD or
coronary artery disease who underwent coronary angiography were included in this
case-control study. Angiograms were reviewed for coronary tortuosity and assigned
a tortuosity score. Tortuosity was common in patients presenting with their first
SCAD event (78% versus 17% in controls; P<0.0001; tortuosity score, 4.41+/-1.73
versus 2.33+/-1.49 in controls; P<0.0001) despite a low prevalence of
hypertension (34%). Recurrent SCAD (n=40) occurred within segments of tortuosity
in 80% of cases. Severe tortuosity (>=2 consecutive curvatures >=180 degrees )
was associated with a higher risk of recurrent SCAD (hazard ratio, 3.29; 95%
confidence interval, 0.99-8.29; P=0.05). Tortuosity score >5 was associated with
a trend toward higher risk of recurrent SCAD (P=0.16). Prespecified angiographic
markers of tortuosity including corkscrew appearance and multivessel symmetrical
tortuosity were associated with extracoronary vasculopathy including
fibromuscular dysplasia (P<0.05 for both). CONCLUSIONS: Coronary artery
tortuosity is highly prevalent in the SCAD population and is associated with
recurrent SCAD. Recurrent SCAD most often occurs within segments of tortuosity.
Angiographic features of SCAD are associated with extracoronary vasculopathy,
including fibromuscular dysplasia. These findings suggest that coronary
tortuosity may serve as a marker or potential mechanism for SCAD.
PMID- 25138035
TI - Effect of single tibial artery revascularization on microcirculation in the
setting of critical limb ischemia.
AB - BACKGROUND: Benefits of 2-dimensional (2D) angiosome-oriented infrapopliteal
revascularization remain controversial. The aim of this retrospective study was
to clarify the effect of single tibial artery revascularization on the dorsal and
plantar microcirculation of critically ischemic limbs based on skin perfusion
pressure (SPP). METHODS AND RESULTS: Fifty-seven interventions that only involved
either anterior tibial artery (ATA) or posterior tibial artery (PTA)
revascularization were included in this study. SPP was measured on the dorsal
side (theoretically ATA perfusion area) and the plantar side (theoretically PTA
perfusion area) before and after the procedure. Dorsal and plantar SPP increased
significantly, from 33 (IQR 23-40.5) to 52 (IQR 32.5-65) mm Hg (P<0.0001) and
31.6+/-16.1 to 44.8+/-19.2 mm Hg (P=0.001) after ATA revascularization,
respectively, and from 29.3+/-14.0 to 42.4+/-19.7 mm Hg (P=0.003) and 29.3+/-9.8
to 43.5+/-15.9 mm Hg (P<0.001) after PTA revascularization, respectively. Both
ATA and PTA revascularization were not associated with any significant
differences in DeltaSPP between the dorsal and the plantar regions of the foot.
Only 64% and 58% of ATA revascularization cases showed higher post-SPP and
DeltaSPP on the dorsal side than on the plantar side, respectively. Also, only
47% and 40% of PTA revascularization cases showed higher post-SPP and DeltaSPP on
the plantar side than on the dorsal side, respectively. CONCLUSIONS: Single
tibial artery revascularization, whether of the ATA or PTA, yielded comparable
improvements in microcirculation of the dorsal and plantar foot. Approximately
half of the feet revascularized had a change in microcirculation that was not
consistent with the 2D angiosome theory.
PMID- 25138036
TI - Management and outcome of metastatic clear cell sarcoma.
PMID- 25138037
TI - Treatment of fracture sequelae of the proximal humerus: comparison of
hemiarthroplasty and reverse total shoulder arthroplasty.
AB - INTRODUCTION: Fracture sequelae (FS) of the proximal humerus is a challenging
scenario in shoulder surgery. Despite they have been traditionally treated with
hemiarthroplasty (HA), the use of reverse shoulder arthroplasty (RSA) has been
recently introduced. However, there are no studies comparing the results of HA
and RSA in FS. The purpose of this study was to compare the functional and
quality of life-related outcomes, and complications in the treatment of proximal
humeral FS between HA and RSA. MATERIALS AND METHODS: A therapeutic prospective
non-randomized comparative study was conducted. All consecutive patients with
diagnosis of FS after non-operative treatment of proximal humeral fractures and
no previous shoulder surgery were considered for this study. A total of 32
patients (24 females, 8 males) with a mean (SD) age at the time of surgery of
80.1 (4.9) years were finally included: 12 in the HA group, and 20 in the RSA
group. FS were treated with shoulder arthroplasty by the implantation of either
HA or RSA. Constant score (total and specific items), quality of life (assessed
through SF-36), and complications requiring revision surgery were compared
between groups. RESULTS: All parameters of the Constant score significantly
improved in the postoperative compared to preoperative period when considering
the entire sample. The RSA group demonstrated a higher improvement in total
Constant score (p = 0.06) and Constant activity level (p = 0.02) compared to the
HA group. The HA demonstrated a higher number of complications compared to the
RSA (p = 0.05). There were no differences in SF-36 scores between both groups.
CONCLUSIONS: The shoulder arthroplasty is an effective treatment for FS with
significant improvement in pain and function. The RSA may be a better option than
HA for FS given the trend towards better total Constant score and a significantly
lower number of complications requiring revision surgery. LEVEL OF EVIDENCE:
Therapeutic level II evidence.
PMID- 25138038
TI - Effects of diesel and kerosene on germination and growth of coastal wetland plant
species.
AB - This study aims to investigate effects of diesel and kerosene on seed germination
and seedling growth among coastal wetland plants to select species that can be
used for the restoration and revegetation of oil-polluted habitats. Tests on 51
species were performed in Petri dishes containing 0 %, 6 %, 12 %, and 18 %
diesel, 20 %, 40 %, and 60 % kerosene; each treatment combination was replicated
five times with 20 seeds in each Petri dish. All dishes were held in a growth
chamber with 20 degrees C day of 12 h/15 degrees C night of 12 h in 80 % humidity
for 20 days for calculating the germination percentage, seedling weight, and
seedling vitality. The germination percentage of Rumex stenophyllus decreased
significantly in diesel and kerosene treatments. The weights of seedlings treated
with diesel and kerosene either increased or decreased in comparison with
controls depending on the species. Vitality percentage values were high for
seedlings of Chenopodium ficifolium. Thus, herbaceous plant responses to oil
treatments are species-specific.
PMID- 25138039
TI - Prevalence comparisons of somatic and psychiatric symptoms between community
nonpatients without pain, acute pain patients, and chronic pain patients.
AB - OBJECTIVES: Somatic/psychiatric symptoms are frequently found in chronic pain
patients (CPPs). The objectives of this study were to determine 1) which
somatic/psychiatric symptoms are more commonly found in acute pain patients
(APPs) and CPPs vs community nonpatients without pain (CNPWPs) and 2) if
somatic/psychiatric symptom prevalence differs between APPs and CPPs. DESIGN: The
above groups were compared statistically for endorsement of 15 symptoms: fatigue,
numbness/tingling, dizziness, difficulty opening/closing mouth, muscle weakness,
difficulty staying asleep, depression, muscle tightness, nervousness,
irritability, memory, falling, nausea, concentration, and headaches. RESULTS:
After controlling for age, gender, and level of pain, APPs and CPPs had a
statistically significantly greater prevalence (at a P < 0.01 level) for 11 and
13 symptoms, respectively, vs CNPWPs. After controlling for age, gender, and
level of pain, CPPs had a statistically significantly greater prevalence (at a P
< 0.01 level) for eight symptoms vs APPs. Symptoms were highly correlated in both
APPs and CPPs. CONCLUSIONS: CPPs are characterized to a significantly greater
extent than comparison groups by somatic/psychiatric symptoms that are highly
intercorrelated. This has implications for clinical practice and future research.
PMID- 25138040
TI - Using and interpreting serum albumin and prealbumin as nutritional markers in
patients on chronic dialysis.
PMID- 25138042
TI - Ser9-phosphorylated GSK3beta induced by 14-3-3zeta actively antagonizes cell
apoptosis in a NF-kappaB dependent manner.
AB - The activity of glycogen synthase kinase beta (GSK3beta) is mainly regulated by
its Ser9 phosphorylation. It has been believed for a long time that Ser9
phosphorylation regulates the functions of GSK3beta through inhibition of its
kinase activity. In this study, we have confirmed the interaction of Ser9
phosphorylated GSK3beta with 14-3-3zeta by using GST pull-down assays. We show
that 14-3-3zeta enhances Ser9 phosphorylation of GSK3beta by PKC. Surprisingly,
using a NF-kappaB luciferase reporter system, we find that Ser9-phosphorylation
of GSK3beta promoted by 14-3-3zeta is critical for the activation of NF-kappaB
pathway, which may thwart the pro-apoptotic activity of GSK3beta. Inhibition of
either NF-kappaB or GSK3beta significantly abolishes the anti-apoptotic effect of
14-3-3zeta and Ser9-phosphorylated GSK3beta, suggesting that Ser9-phosphorylated
GSK3beta actively antagonizes cell apoptosis in a NF-kappaB dependent manner.
PMID- 25138041
TI - Influence of irradiation time on subsurface degree of conversion and
microhardness of high-viscosity bulk-fill resin composites.
AB - OBJECTIVES: To evaluate the influence of irradiation time on degree of conversion
(DC) and microhardness of high-viscosity bulk-fill resin composites in depths up
to 6 mm. MATERIALS AND METHODS: Four bulk-fill materials (Tetric EvoCeram Bulk
Fill--TECBF; x-tra fil--XF; QuixFil--QF; SonicFill-SF) and one conventional nano
hybrid resin composite (Tetric EvoCeram--TEC) were irradiated for 10, 20, or 30 s
at 1,170 mW/cm(2). DC and Knoop microhardness (KHN) were recorded after 24-h dark
storage at five depths: 0.1, 2, 4, 5, and 6 mm. Data were statistically analyzed
using ANOVA and Bonferroni's post-hoc test (alpha = 0.05). RESULTS: With
increasing bulk thickness, DC and KHN significantly decreased for TEC. TECBF and
SF showed a significant decrease in DC and KHN at 4-mm depth after 10-s
irradiation, but no decrease in DC after 30-s irradiation (p > 0.05). XF and QF
demonstrated no significant DC decrease at depths up to 6 mm after irradiation of
at least 20 s. At 4-mm depth, all materials tested achieved at least 80 % of
their maximum DC value, irrespective of irradiation time. However, at the same
depth (4 mm), only XF and QF irradiated for 30 s achieved at least 80 % of their
maximum KHN value. CONCLUSIONS: Regarding DC, the tested bulk-fill resin
composites can be safely used up to at least 4-mm incremental thickness. However,
with respect to hardness, only XF and QF achieved acceptable results at 4-mm
depth with 30 s of irradiation. CLINICAL RELEVANCE: Minimum irradiation times
stated by the manufacturers cannot be recommended for placement of high-viscosity
bulk-fill materials in 4-mm increments.
PMID- 25138043
TI - The economic burden of time-loss injuries to youth players participating in week
long rugby union tournaments.
AB - OBJECTIVES: Rugby Union ("rugby") is a popular sport with high injury risk.
Burden of injury is described by the incidence and severity of injury. However
reports have ignored the monetary cost of injuries. Therefore the aim of this
study was to describe the monetary cost associated with youth rugby injuries.
DESIGN: This descriptive study quantified medical treatments of injured players
at the South African Rugby Union Youth tournaments in 2011/2012 and the days of
work parents missed as a result of the injuries. A health insurer used these data
to calculate associated costs. METHODS: Legal guardians of the 421 injured
players were contacted telephonically on a weekly basis until they returned to
play. Treatments costs were estimated in South African Rands based on 2013
insurance rates and converted to US$ using purchasing power parities. RESULTS: Of
the 3652 players, 2% (n=71) sought medical care after the tournament. For these
players, average treatment costs were high (US$731 per player, 95% CI: US$425
US$1096), with fractures being the most expensive type of injury. Players with
medical insurance had higher costs (US$937, 95% CI: US$486-US$1500) than those
without (US$220, 95% CI: US$145-US$302). CONCLUSIONS: Although a minority of
players sought follow-up treatment after the tournaments, the cost of these
injuries was high. Players without medical insurance having lower costs may
indicate that these players did not receive adequate treatment for their
injuries. Injury prevention efforts should consider injuries with high costs and
the treatment of players without medical insurance.
PMID- 25138044
TI - The coupling of tautomerization to hydration in the transition state on the
pyrimidine photohydration reaction path.
AB - The ground state reaction path for formation of the pyrimidine hydrates was
calculated using a nudged elastic band (NEB) approach, combined with a
calculation of the transition state, and implemented using a numerical basis set
in the density functional theory (DFT) code DMol(3). The model systems used for
study consist of 1-methyl pyrimidines with a H2O molecule as the reactant, and
the corresponding C5-hydro-C6-hydroxypyrimidine as the product. The barrier to
addition of water across the C5-C6 pi-bond ranges from 43-48 kcal mol(-1) in the
1-methylpyrimidines (1-MP) studied. Similar but slightly smaller barriers of 34
45 kcal mol(-1) were found for the tautomers of the 1-MPs, i.e. the enols of
uridine and thymine and imine of cytosine. Comparison of these calculations with
previous computational and experimental work suggests that a hot ground state
formed by the rapid internal conversion of pyrimidines has sufficient energy to
permit crossover from the common form to the tautomeric form of the pyrimidine at
the transition state. The hot ground state mechanism can account for the
experimentally observed yield and thermal reversion of pyrimidine photohydrates,
while simultaneously explaining the effect of photohydrates on the mutation rate.
PMID- 25138045
TI - Effect of different assumptions for brain water content on absolute measures of
cerebral oxygenation determined by frequency-domain near-infrared spectroscopy in
preterm infants: an observational study.
AB - BACKGROUND: Brain-water content (BWC) decreases with maturation of the brain and
potentially affects parameters of cerebral oxygenation determined by near
infrared spectroscopy (NIRS). Most commercially available devices do not take
these maturational changes into account. The aim of this study was to determine
the effect of different assumptions for BWC on parameters of cerebral oxygenation
in preterm infants. METHODS: Concentrations of oxy-, deoxy- and total hemoglobin
and regional cerebral oxygen saturation (rcStO2) were calculated based on
absolute coefficients of absorption and scattering determined by multi-distance
Frequency-Domain-NIRS assuming BWCs of 75-95%, which may be encountered in
newborn infants depending on gestational and postnatal age. RESULTS: This range
of BWC gave rise to a linear modification of the assessed NIRS parameters with a
maximum change of 10%. This may result in an absolute overestimation of rcStO2 by
(median (range)) 4 (1-8)%, if the calculation is based on the lowest BWC (75%) in
an extremely preterm infant with an anticipated BWC of 95%. CONCLUSION:
Clinicians wishing to rely on parameters of cerebral oxygenation determined by
NIRS should consider that maturational changes in BWC not taken into account by
most devices may result in a deviation of cerebral oxygenation readings by up to
8% from the correct value.
PMID- 25138046
TI - Effect of atrazine and fenitrothion at no-observed-effect-levels (NOEL) on
amphibian and mammalian corticosterone-binding-globulin (CBG).
AB - This study determines the effect of atrazine and fenitrothion no-observed-effect
levels (NOEL) on the binding of corticosterone (B) to corticosterone-binding
globulin (CBG) in an amphibian and a mammal. Plasma from five cane toads and five
Wistar rats was exposed to atrazine and fenitrothion at the NOEL approved for
Australian fresh water residues and by the World Health Organization (WHO). The
concentration required to displace 50% (IC50) of B binding to CBG was determined
by a competitive microdialysis protein assay. Competition studies showed that
both atrazine and fenitrothion at NOEL are able to compete with B for CBG binding
sites in toad and rat plasma. The IC50 levels for atrazine in toads and rats were
0.004 nmol/l and 0.09 nmol/l respectively. In the case of fenitrothion the IC50
level found in toads was 0.007 nmol/l, and 0.025 nmol/l in rats. Plasma dilution
curves showed parallelism with the curve of B, demonstrating that these agro
chemicals are competitively inhibiting binding to CBG. The displacement of B by
atrazine and fenitrothion would affect the total:free ratio of B and consequently
disrupt the normal stress response. This is the first time that the potential
disruptive effect of atrazine and fenitrothion on B-CBG interaction at the NOELs
has been demonstrated in amphibian and mammalian models.
PMID- 25138047
TI - The reliability of fetal MRI in the assessment of brain malformations.
AB - OBJECTIVES: To assess the inter- and intraobserver reliability of different fetal
MRI measurements in cases of fetal brain malformations and to examine the
concordance between ultrasonography (US) and MRI findings. METHODS: Fetal brain
MRIs and US findings of 56 pregnant women were retrieved from the institutional
database. Standardized fetal brain MRI measurements were performed by 4
observers, and the inter- and intraobserver reliability was determined.
Additionally, US and MRI findings were retrospectively compared. RESULTS: The
interobserver intraclass correlation coefficient (ICC) was above 0.9 for the
cerebellum and posterior horn of the lateral ventricle. The measurements
regarding the third ventricle (0.50), the fourth ventricle (0.58), and the corpus
callosum (0.63) showed poor reliability. Overall, the intraobserver reliability
was greater than the interobserver reliability. US and MRI findings were
discordant in 29% of the cases with MRI rendering an extended diagnosis in 18%, a
change of diagnosis in 3.6%, and excluding pathological findings suspected on US
in 7.1%. CONCLUSIONS: Fetal MRI is a valuable complement to US in the
investigation of fetal brain malformations. The reliability of most parameters
was high, except for the measurements of the third and fourth ventricles and the
corpus callosum.
PMID- 25138048
TI - Targeting primary mediastinal B-cell lymphoma.
PMID- 25138049
TI - 'Sex' in the cancer cell.
PMID- 25138050
TI - Deletion of Ptprd and Cdkn2a cooperate to accelerate tumorigenesis.
AB - PTPRD encodes the protein tyrosine phosphatase receptor type D and is frequently
inactivated across many human cancers. Despite its frequent inactivation, it is
unknown whether loss of PTPRD promotes tumorigenesis in vivo. PTPRD is located on
chromosome 9p, as is CDKN2A, and the two loci are frequently deleted together.
Here, we show that co-deletion of Ptprd and Cdkn2a cooperate to accelerate
tumorigenesis. Interestingly,heterozygous loss of Ptprd was sufficient to promote
tumorigenesis in our model, suggesting that Ptprd may be a haploinsufficient
tumor suppressor. The loss of Ptprd resulted in changes to the tumor spectrum in
mice and increased the frequency of lymphomas. In total, we reveal that Ptprd is
a tumor suppressor that can promote tumorigenesis in concert with Cdkn2a loss.
PMID- 25138051
TI - Denosumab mimics the natural decoy receptor osteoprotegerin by interacting with
its major binding site on RANKL.
AB - Bone homeostasis critically relies on the RANKL-RANK-OPG axis which can be
targeted by the fully human monoclonal antibody denosumab in conditions with
increased bone resporption such as bone metastases. The binding site and
therefore the molecular mechanism by which this antibody inhibits RANKL has not
been characterized so far. Here, we used random peptide phage display library
screenings to identify the denosumab epitope on RANKL. Alignments of phage
derived peptide sequences with RANKL suggested that this antibody recognized a
linear epitope between position T233 and Y241. Mutational analysis confirmed the
core residues as critical for this interaction. The spatial localization of this
epitope on a 3-dimensional model of RANKL showed that it overlapped with the
major binding sites of OPG and RANK on RANKL. We conclude that denosumab inhibits
RANKL by both functional and molecular mimicry of the natural decoy receptor OPG.
PMID- 25138054
TI - Recurrence of a Delayed-Onset Posttraumatic Renal Pseudoaneurysm after Initially
Successful Transarterial Embolization.
AB - Hemodynamically stable patients with renal injury can be managed conservatively.
Anatomy typically leads to physiologic confinement of urinomas or renal hematomas
to the interfascial planes of the retroperitoneum. In the presented case there
was unusual reperfusion 14 days after a successful embolization of a renal
pseudoaneurysm, at this time 28 days after the initiating trauma. This article
discusses the evolution, treatment options and possible underlying causes for the
reperfusion of this late-onset renal pseudoaneurysm.
PMID- 25138052
TI - Inhibition of lung tumor growth by targeting EGFR/VEGFR-Akt/NF-kappaB pathways
with novel theanine derivatives.
AB - The molecularly targeted agents, including anti-VEGF or anti-EGFR monoclonal
antibody and some inhibitors of EGFR tyrosine kinase, are effective in the
treatment of non-small-cell lung cancer (NSCLC) to a certain extent, but the
benefit for a proportion of patients is still limited. Hence, it is necessary and
urgent to develop more selective and effective molecular targeted agents against
lung cancer. Here, we have synthesized novel theanine derivatives, methyl
coumarin-3-carboxylyl L-theanine (TMC), ethyl coumarin-3-carboxylyl L-theanine
(TEC), ethyl 6-fluorocoumarin- 3-carboxylyl L-theanine (TFC), and ethyl 6
nitrocoumarin-3-carboxylyl L-theanine (TNC), which are fluorescent small
molecules, based on their parental compound theanine and studied their anticancer
activities in vitro, ex vivo and in vivo models of human and mouse cancers. Our
results show that the four theanine derivatives significantly inhibit the lung
cancer cell migration and the growth of lung cancer and leukemia cell lines. TFC
and TNC display enhanced effects with anticancer drugs cytarabine vincristine,
andmethotrexate on inhibition of lung cancer cell growth and no toxicity to the
normal human embryonic lung fibroblast and peripheral blood lymphocytes. TFC and
TNC exhibit strong suppression of the highly metastatic Lewis lung cancer (LLC)
and A549 tumor growth in tumor-bearing mice without toxicity to mice. TFC and TNC
can effectively suppress the growth of lung cancer cells in vitro, ex vivo and in
vivo by targeting EGFR/VEGFR-Akt/NF-kappaB pathways. Our study has suggested that
TFC and TNC may have the therapeutic and/or adjuvant therapeutic applications in
the treatment of lung cancers and other cancer.
PMID- 25138053
TI - Clusterin inhibition using OGX-011 synergistically enhances zoledronic acid
activity in osteosarcoma.
AB - PURPOSE: Despite recent improvements in therapeutic management of osteosarcoma,
ongoing challenges in improving the response to chemotherapy warrants new
strategies still needed to improve overall patient survival. Among new
therapeutic approaches, zoledronic acid (ZOL) represents a promising adjuvant
molecule to chemotherapy to limit the osteolytic component of bone tumors.
However, ZOL triggers the elevation of heat shock proteins (Hsp), including Hsp27
and clusterin (CLU), which could enhance tumor cell survival and treatment
resistance. We hypothesized that targeting CLU using siRNA or the antisense drug,
OGX-011, will suppress treatment-induced CLU induction and enhance ZOL-induced
cell death in osteosarcoma (OS) cells. METHODS: The combined effects of OGX-011
and ZOL were investigated in vitro on cell growth, viability, apoptosis and cell
cycle repartition of ZOL-sensitive or -resistant human OS cell lines (SaOS2,
U2OS, MG63 and MNNG/HOS). RESULTS: In OS cell lines, ZOL increased levels of
HSPs, especially CLU, in a dose- and time-dependent manner by mechanism including
increased HSF1 transcription activity. The OS resistant cells to ZOL exhibited
higher CLU expression level than the sensitive cells. Moreover, CLU
overexpression protects OS sensitive cells to ZOL-induced cell death by
modulating the MDR1 and farnesyl diphosphate synthase expression. OGX-011
suppressed treatment-induced increases in CLU and synergistically enhanced the
activity of ZOL on cell growth and apoptosis. These biologic events were
accompanied by decreased expression of HSPs, MDR1 and HSF1 transcriptional
activity. In vivo, OGX-011, administered 3 times a week (IP, 20mg/kg),
potentiated the effect of ZOL (s.c; 50ug/kg), significantly inhibiting tumor
growth by 50% and prolonging survival in MNNG/HOS xenograft model compared to ZOL
alone. CONCLUSION: These results indicate that ZOL-mediated induction of CLU can
be attenuated by OGX-011, with synergistic effects on delaying progression of
osteosarcoma.
PMID- 25138056
TI - The psychometric properties of the St George's Respiratory Questionnaire (SGRQ)
in patients with idiopathic pulmonary fibrosis: a literature review.
AB - Assessment of health-related quality of life (HRQL) is particularly important in
patients with progressive and incurable diseases such as idiopathic pulmonary
fibrosis (IPF). The St George's Respiratory Questionnaire (SGRQ) has frequently
been used to measure HRQL in patients with IPF, but it was developed for patients
with obstructive lung diseases. The aim of this review was to examine published
data on the psychometric performance of the SGRQ in patients with IPF. A
comprehensive search was conducted to identify studies reporting data on the
internal consistency, construct validity, test-retest reliability, and
interpretability of the SGRQ in patients with IPF, published up to August 2013.
In total, data from 30 papers were reviewed. Internal consistency was moderate
for the SGRQ symptoms score and excellent for the SGRQ activity, impact and total
scores. Validity of the SGRQ symptoms, activity, impact and total scores was
supported by moderate to strong correlations with other patient-reported outcome
measures and with a measure of exercise capacity. Most correlations were
moderately strong between SGRQ activity or total scores and forced or static
vital capacity, the most commonly used marker of IPF severity. There was evidence
that changes in SGRQ domain and total scores could detect within-subject
improvement in health status, and differentiate groups of patients whose health
status had improved, declined or remained unchanged. Although the SGRQ was not
developed specifically for use with patients with IPF, on balance, its
psychometric properties are adequate and suggest that it may be a useful measure
of HRQL in this patient population. However, several questions remain
unaddressed, and further research is needed to confirm the SGRQ's utility in IPF.
PMID- 25138057
TI - Serum microRNA-29 levels correlate with disease progression in patients with
chronic hepatitis B virus infection.
AB - OBJECTIVE: To investigate the role of serum microRNA-29 (miR-29) as a biomarker
for the prediction of disease progression in patients with chronic hepatitis B
virus (HBV) infection. METHODS: Using real-time quantitative polymerase chain
reaction assay, serum miR-29a, miR-29b and miR-29c levels were measured in
patients with chronic HBV infection, and the correlation between serum miR-29
levels and the participants' liver biochemistry, fibrotic stage and
necroinflammation grade were also evaluated. RESULTS: Altogether 91 patients with
chronic HBV infection were divided by fibrotic stage into S0/1 (no or mild
fibrosis), S2/3 (progressive fibrosis) and S4 (cirrhosis) subgroups, and 12
healthy individuals were also included in the study. Serum miR-29a and miR-29c in
S0-3 were significantly higher than those in S4 patients (P < 0.001); however,
the difference between S0/1 and S2/3 patients was not significant. miR-29b levels
were higher in S0/1 patients than in other patient groups, but did not differ
between S2/3 and S4 patients. At fibrotic stages of S0/1 and S2/3, patients with
no or mild liver inflammation (G0/1) tended to express higher miR-29 levels than
those with advanced inflammation (G2-4) (P > 0.05). miR-29a-c showed significant
correlation with alanine transaminase levels (P < 0.05 for miR-29a, miR-29b and
miR-29c) in S0-3 patients. The expression of miR-29 was highest in immune
tolerant patients (P < 0.001). CONCLUSIONS: Serum miR-29 levels are negatively
correlated with liver fibrotic stages and necroinflammation grades in patients
with chronic HBV infection. miR-29 appears to be a novel biomarkers for
predicting disease progression in these patients.
PMID- 25138055
TI - PET imaging in ischemic cerebrovascular disease: current status and future
directions.
AB - Cerebrovascular diseases are caused by interruption or significant impairment of
the blood supply to the brain, which leads to a cascade of metabolic and
molecular alterations resulting in functional disturbance and morphological
damage. These pathophysiological changes can be assessed by positron emission
tomography (PET), which permits the regional measurement of physiological
parameters and imaging of the distribution of molecular markers. PET has
broadened our understanding of the flow and metabolic thresholds critical for the
maintenance of brain function and morphology: in this application, PET has been
essential in the transfer of the concept of the penumbra (tissue with perfusion
below the functional threshold but above the threshold for the preservation of
morphology) to clinical stroke and thereby has had great impact on developing
treatment strategies. Radioligands for receptors can be used as early markers of
irreversible neuronal damage and thereby can predict the size of the final
infarcts; this is also important for decisions concerning invasive therapy in
large ("malignant") infarctions. With PET investigations, the reserve capacity of
blood supply to the brain can be tested in obstructive arteriosclerosis of the
supplying arteries, and this again is essential for planning interventions. The
effect of a stroke on the surrounding and contralateral primarily unaffected
tissue can be investigated, and these results help to understand the symptoms
caused by disturbances in functional networks. Chronic cerebrovascular disease
causes vascular cognitive disorders, including vascular dementia. PET permits the
detection of the metabolic disturbances responsible for cognitive impairment and
dementia, and can differentiate vascular dementia from degenerative diseases. It
may also help to understand the importance of neuroinflammation after stroke and
its interaction with amyloid deposition in the development of dementia. Although
the clinical application of PET investigations is limited, this technology had
and still has a great impact on research into cerebrovascular diseases.
PMID- 25138058
TI - Ranolazine as a promising treatment option for atrial fibrillation:
electrophysiologic mechanisms, experimental evidence, and clinical implications.
AB - Currently available agents for pharmacologic management of atrial fibrillation
(AF) are limited by their suboptimal efficacy and nonnegligible proarrhythmic
risk. Ranolazine (RN) is a novel antianginal agent with increasingly appreciated
antiarrhythmic properties that can suppress ventricular and supraventricular
arrhythmias including AF. In this review, we describe the electrophysiological
properties of RN, focusing on atrial-selective inhibition of a number of ion
channels implicated in the development of AF, particularly the sodium current. We
further summarize evidence from experimental studies that demonstrate a potent AF
suppressing effect of RN, alone or in combination with other antiarrhythmic
drugs. Of clinical relevance, we present growing evidence from preliminary
clinical investigations indicating the safety and efficacy of RN for prevention
and treatment of AF in various clinical settings including prevention of AF in
patients with acute coronary syndromes, prevention and conversion of
postoperative AF after surgical coronary revascularization, sinus rhythm
maintenance in drug-resistant recurrent AF, and facilitating of electrical or
pharmacological cardioversion in cardioversion-resistant patients. While current
experimental and clinical evidence points to RN as a potentially promising agent
for suppression of AF, well-designed, large-scale trials will be required before
RN can be considered for pharmacological treatment of AF in clinical practice.
PMID- 25138059
TI - Adolescent chronic pain and association to perinatal factors: linkage of Birth
Registry data with the Young-HUNT Study.
AB - BACKGROUND: The aim of this study was to examine the associations of birthweight,
gestation and 5-min Apgar score with self-reported chronic nonspecific pain in a
large, unselected adolescent population. METHODS: The third population-based Nord
Trondelag Health Study (HUNT) included 8200 adolescents aged 13-19 years,
constituting 78.2% of adolescents in Nord-Trondelag County. In the target age
group, 13-18 years, data on pain frequency from 10 localizations were available
from 7373 adolescents. Chronic nonspecific pain was defined as pain at least once
a week during the last 3 months, not related to any known disease or injury.
Chronic multisite pain was defined as chronic pain in at least three
localizations, and chronic daily pain was defined as chronic pain almost every
day. Perinatal data were retrieved from the Medical Birth Registry of Norway, and
data were available for 7120 of the 7373 adolescents. Covariates included
adolescent and maternal general health measures from the HUNT study. RESULTS: We
found no consistent association between preterm birth and chronic pain and no
clear association between birthweight and chronic pain complaints in adolescence.
Post-term birth in boys and a low 5-min Apgar score in both sexes tended to
increase the reporting of chronic pain in adolescence. CONCLUSIONS: Perinatal
factors, and especially preterm birth and low birthweight, did not seem to have a
major impact on pain complaints in adolescence.
PMID- 25138061
TI - Pharmacokinetics and efficacy of darunavir/ritonavir once daily in virologically
suppressed, treatment-experienced HIV-infected children.
PMID- 25138062
TI - Acid-promoted chemoselective introduction of amide functionality onto aromatic
compounds mediated by an isocyanate cation generated from carbamate.
AB - Carbamates have been used as precursors of isocyanates, but heating in the
presence of strong acids is required because cleavage of the C-O bond in
carbamates is energy-demanding even in acid media. Direct amidation of aromatic
compounds by isocyanate cations generated at room temperature from carbamoyl
salicylates in trifluoromethanesulfonic acid (TfOH) was examined. Carbamates with
ortho-salicylate as an ether group (carbamoyl salicylates) showed dramatically
accelerated O-C bond dissociation in TfOH, which resulted in facile generation of
the isocyanate cation. These chemoselective intermolecular aromatic amidation
reactions proceeded even at room temperature and showed good compatibility with
other electrophilic functionalities and high discrimination between N
monosubstituted carbamate and N,N-disubstituted carbamate. The reaction rates of
secondary and tertiary amide formation were markedly different, and this
difference was utilized to achieve successive (tandem) amidation reactions of
molecules with an N-monosubstituted carbamate and an N,N-disubstituted carbamate
with two kinds of aromatic compounds.
PMID- 25138060
TI - Star-shaped poly(L-lactide)-b-poly(lactobionamidoethyl methacrylate) with
porphyrin core: synthesis, self-assembly, singlet oxygen research and recognition
properties.
AB - Star-shaped porphyrin-cored poly(L-lactide)-b-poly(lactobionamidoethyl
methacrylate) block copolymers (SPPLA-b-PLAMA) were synthesized via RAFT of
unprotected Lactobionamidoethyl methacrylate (LAMA) in 1-methyl-2-pyrrolidinone
(NMP) solution at 70 degrees C. The structure of this as-synthesized SPPLA-b
PLAMA block copolymer was thoroughly studied by nuclear magnetic resonance
spectroscopy, gel permeation chromatography (GPC), and Fourier transforms
infrared. Moreover, under the irradiation, such SPPLA-b-PGAMA copolymer exhibits
efficient singlet oxygen generation (0.17) and indicates high fluorescence
quantum yields (0.20). Notably, with UV-vis investigation, SPPLA-b-PLAMA showed a
very specific recognition with RCA120 lectin. This will not only provide
potentially prophyrin-cored star-shaped SPPLA-b-PLAMA block copolymers for
targeted photodynamic therapy, but also improve the physical, biodegradation,
biocompatibility properties of PLA-based biomaterials.
PMID- 25138063
TI - High- but not low-intensity light leads to oxidative stress and quality loss of
cold-stored baby leaf spinach.
AB - BACKGROUND: Quality management in the fresh produce industry is an important
issue. Spinach is exposed to various adverse conditions (temperature, light,
etc.) within the supply chain. The present experiments were conducted to
investigate the effect of light conditions (dark, low-intensity light (LL) and
high-intensity light (HL)) and photoperiod (6 h HL and 18 h dark) on the quality
changes of cold-stored spinach. RESULTS: HL exposure resulted in oxidative
stress, causing tissue damage and quality loss as evidenced by increased membrane
damage and water loss. The content of total ascorbic acid was reduced under HL
conditions. On the other hand, storage of spinach under LL conditions gave
promising results, as nutritional quality was not reduced, while texture
maintenance was improved. No significant differences, with the exception of
nutritional quality, were found between spinach leaves stored under continuous
(24 h) low-intensity light (30-35 umol m(-2) s(-1)) and their counterparts stored
under the same light integral over 6 h (130-140 umol m(-2) s(-1)). CONCLUSION: LL
extended the shelf-life of spinach. The amount of light received by the leaves
was the key factor affecting produce quality. Light intensity, however, has to be
low enough not to cause excess oxidative stress and lead to accelerated
senescence.
PMID- 25138064
TI - Effect of almond consumption on the serum fatty acid profile: a dose-response
study.
AB - Consumption of almonds has been shown to be associated with a decreased risk of
CHD, which may be related to their fatty acid (FA) composition. However, the
effect of almond consumption on the serum FA composition is not known. Therefore,
in the present study, we investigated whether almond consumption would alter the
serum FA profile and risk of CHD, as calculated using Framingham's 10-year risk
score, in a dose-dependent manner in hyperlipidaemic individuals when compared
with a higher-carbohydrate control group using dietary interventions
incorporating almonds. A total of twenty-seven hyperlipidaemic individuals
consumed three isoenergetic (mean 1770 kJ/d) supplements during three 1-month
dietary phases: (1) full-dose almonds (50-100 g/d); (2) half-dose almonds with
half-dose muffins; (3) full-dose muffins. Fasting blood samples were obtained at
weeks 0 and 4 for the determination of FA concentrations. Almond intake (g/d) was
found to be inversely associated with the estimated Framingham 10-year CHD risk
score (P= 0.026). In both the half-dose and full-dose almond groups, the
proportions of oleic acid (OA) and MUFA in the TAG fraction (half-almond: OA P=
0.003; MUFA P= 0.004; full-almond: OA P< 0.001; MUFA P< 0.001) and in the NEFA
fraction (half-almond: OA P= 0.01; MUFA P= 0.04; full-almond: OA P= 0.12; MUFA P=
0.06) increased. The estimated Framingham 10-year CHD risk score was inversely
associated with the percentage change of OA (P= 0.011) and MUFA (P= 0.016)
content in the TAG fraction. The proportions of MUFA in the TAG and NEFA
fractions were positively associated with changes in HDL-cholesterol
concentrations. Similarly, the estimated Framingham 10-year CHD risk score was
inversely associated with the percentage change of OA (P= 0.069) and MUFA content
in the NEFA fraction (P= 0.009). In conclusion, the results of the present study
indicate that almond consumption increases OA and MUFA content in serum TAG and
NEFA fractions, which are inversely associated with CHD lipid risk factors and
overall estimated 10-year CHD risk.
PMID- 25138065
TI - CXCL13 as a new biomarker of systemic lupus erythematosus and lupus nephritis -
from bench to bedside?
AB - Different studies over the last decade have linked the B cell-attracting
chemokine CXC ligand 13 (CXCL13) to the autoimmune disease systemic lupus
erythematosus (SLE). A pathogenetic role of this chemokine for disease
manifestation in SLE was described initially in mouse models for SLE. Mechanisms
of CXCL13 actions were also identified in SLE patients. Moreover, various
clinical studies have identified CXCL13 serum levels as a useful biomarker in
patients with SLE of different ethnicities for disease activity. In addition,
CXCL13 seems to be a promising marker for the diagnosis of lupus nephritis, one
of the most severe complications of SLE. However, its exact place within the
mechanisms that lead to SLE remains to be defined. Further research is needed to
resolve more details of the pathomechanism and the signalling pathway of CXCL13
in SLE. Blocking CXCL13 or the signal pathways of CXCL13 is seen as a promising
therapeutic approach for SLE and will be addressed in the near future. This
review summarizes all papers that linked CXCL13 to SLE and highlights its
importance in the pathogenesis and diagnosis of SLE.
PMID- 25138066
TI - Hyalurosome gene regulation and dose-dependent restoration of skin atrophy by
retinaldehyde and defined-size hyaluronate fragments in dermatoporosis.
AB - BACKGROUND: Dermatoporosis is an emerging clinical condition caused by
chronological skin aging, long-term sun exposure and chronic use of
corticosteroids; however, genomic expression in dermatoporosis and the efficacy
of different therapeutic approaches to prevent and treat dermatoporosis have not
been investigated so far. OBJECTIVE: We examined the possible effect of topical
retinaldehyde (RAL) and defined-size hyaluronate fragments (HAFi) on the
expression of hyalurosome genes potentially involved in the pathogenesis of
dermatoporosis. We also explored the effect of different concentrations of HAFi
on skin thickness. METHODS: 13 persons were separated into a young control group
(n = 8) and a dermatoporosis group (n = 5). Topical treatment of both groups with
a combination of 0.05% RAL and 1 or 0.2% HAFi was applied on the forearm twice
daily for 30 days. Forearm skin biopsies of both groups were performed before and
after application. Hyalurosome genes CD44, heparin-binding epidermal growth
factor (HB-EGF), ErbB1, hyaluronate synthase 3 (HAS3) and Hyal2 were chosen as
potential markers of dermatoporosis. Quantitative real-time polymerase chain
reaction (qRT-PCR) was performed for quantification of mRNA expression of the
target hyalurosome genes. Measurement of forearm skin thickness before and after
treatment was performed by ultrasonography. Analysis of the results was done by
Student's t test. A p value <0.05 was considered statistically significant.
RESULTS: In qRT-PCR analysis the relative expression of hyalurosome (CD44, HAS3,
HB-EGF) genes was found to be reduced in patients prior to topical treatment and
to be notably increased following treatment. The reduced expression of CD44 and
HAS3 in patients was specifically restored in dermatoporotic patients after
treatment. No difference in skin thickness was observed in controls after
treatment. The treatment caused a significant increase in skin thickness in
dermatoporotic patients. This increase was more significant with 1% HAFi when
compared to 0.2% HAFi. RAL and HAFi also caused a significant reduction in
purpuric lesions in patients with dermatoporosis. CONCLUSION: Our results
indicate that topically applied RAL and HAFi regulate hyalurosome gene expression
in dermatoporosis and that they show a dose-dependent effect on the correction of
skin atrophy in dermatoporotic patients.
PMID- 25138067
TI - Differential accumulation of callose, arabinoxylan and cellulose in nonpenetrated
versus penetrated papillae on leaves of barley infected with Blumeria graminis f.
sp. hordei.
AB - In plants, cell walls are one of the first lines of defence for protecting cells
from successful invasion by fungal pathogens and are a major factor in basal host
resistance. For the plant cell to block penetration attempts, it must adapt its
cell wall to withstand the physical and chemical forces applied by the fungus.
Papillae that have been effective in preventing penetration by pathogens are
traditionally believed to contain callose as the main polysaccharide component.
Here, we have re-examined the composition of papillae of barley (Hordeum vulgare)
attacked by the powdery mildew fungus Blumeria graminis f. sp. hordei (Bgh) using
a range of antibodies and carbohydrate-binding modules that are targeted to cell
wall polysaccharides. The data show that barley papillae induced during infection
with Bgh contain, in addition to callose, significant concentrations of cellulose
and arabinoxylan. Higher concentrations of callose, arabinoxylan and cellulose
are found in effective papillae, compared with ineffective papillae. The papillae
have a layered structure, with the inner core consisting of callose and
arabinoxylan and the outer layer containing arabinoxylan and cellulose. The
association of arabinoxylan and cellulose with penetration resistance suggests
new targets for the improvement of papilla composition and enhanced disease
resistance.
PMID- 25138069
TI - Genetic analysis of Enterobius vermicularis isolated from a chimpanzee with
lethal hemorrhagic colitis and pathology of the associated lesions.
AB - Human pinworms, Enterobius vermicularis, are normally recognized as minor
pathogens. However, a fatal case of human pinworm infection has been reported in
a nonhuman primate, a zoo reared chimpanzee. Here, we histopathologically
examined the lesions in tissues from the deceased chimpanzee and genetically
characterized the isolated worms to investigate the pathogenicity and determine
the phylogeny. We identified ulcers deep in the submucosa where many parasites
were found to have invaded the lamina propria mucosa or submucous tissue. An
inflammatory reaction consisting mainly of neutrophils and lymphocytes but not
eosinophils was observed around the parasites, and intense hemorrhage in the
lamina propria was confirmed. The parasites were morphologically similar to E.
vermicularis based on the shape of the copulatory spicules. Mitochondrial
cytochrome c oxidase subunit 1 gene products were amplified from worm DNA by PCR
and were genetically identified as E. vermicularis based on >98.7% similarity of
partial sequences. Phylogenetic analysis revealed that the sequences clustered
together with other chimpanzee E. vermicularis isolates in a group which has been
referred to as type C and which differs from human isolates (type A). The samples
were negative for bacterial pathogens and Entamoeba histolytica indicating that
E. vermicularis could be pathogenic in chimpanzees. Phylogenetic clustering of
the isolates indicated that the parasite may be host specific.
PMID- 25138070
TI - Exsheathment and midgut invasion of nocturnally subperiodic Brugia malayi
microfilariae in a refractory vector, Aedes aegypti (Thailand strain).
AB - Exsheathment and midgut invasion of nocturnally subperiodic Brugia malayi
microfilariae were analyzed using light and scanning electron microscopy in a
refractory vector, Aedes aegypti (Thailand strain). Results showed that
exsheathed microfilariae represented only approximately 1% of the total
microfilaria midguts dissected at 5-min post-infected blood meal (PIBM). The
percentage of exsheathed microfilariae found in midguts progressively increased
to about 20, 60, 80, 90, and 100% at 1-, 2-5-, 6-12-, 18-36-, and 48-h PIBM,
respectively. Importantly, all the microfilariae penetrating the mosquito midguts
were exsheathed. Midgut invasion by the exsheathed microfilariae was observed
between 2- and 48-h PIBM. SEM analysis revealed sheathed microfilariae surrounded
by small particles and maceration of the microfilarial sheath in the midguts,
suggesting that the midguts of the refractory mosquitoes might have protein(s)
and/or enzyme(s) and/or factor(s) that induce and/or accelerate exsheathment. The
microfilariae penetrated the internal face of the peritrophic matrix (PM) by
their anterior part and then the midgut epithelium, before entering the hemocoel
suggesting that PM was not a barrier against the microfilariae migrating towards
the midgut. Melanized microfilariae were discovered in the hemocoel examined at
96-h PIBM suggesting that the refractory mosquitoes used melanization reactions
against this parasite. This study provided evidence that A. aegypti (Thailand
strain) has refractory mechanisms against B. malayi in both midgut and hemocoel.
PMID- 25138071
TI - Outcomes of repeat laparoscopic liver resection compared to the primary
resection.
AB - BACKGROUND: Repeat laparoscopic liver resection (R-LLR) can be technically
challenging. Data on this topic are scarce and many investigators would question
its feasibility and outcomes. The aim of the present study was to evaluate the
safety, feasibility, oncological efficiency and outcomes of R-LLR. METHODS: We
reviewed a prospectively collected database of 403 patients undergoing 422
laparoscopic liver resections (LLRs) from August 2003 to August 2013. Data of 19
patients undergoing R-LLR were analyzed and compared to the primary resection (P
LLR) in these patients. Demographic and clinical data were studied. A subgroup
analysis was done for minor resections. RESULTS: Twenty R-LLRs were performed in
19 patients (female 58 %; mean age: 57.5 years; age range: 23-79 years).
Colorectal liver metastases (CRLM) were the commonest indication for R-LLR (60
%), followed by neuroendocrine tumor liver metastases (NETLM) (20 %) and
hepatocellular carcinoma (HCC) (10 %). The majority (90 %) of resections were for
malignant disease (18/20). There were three conversions (15 %), and two patients
developed complications (10 %). The operative time (p = 0.005) and blood loss (p
= 0.03) were both significantly greater in R-LLR compared to P-LLR, whereas
length of stay (median 4 days; p = 0.30) and complications (p = 0.58) did not
differ between the groups. R0 resection rates for P-LLR and R-LLR were 95 and 90
%, respectively (p = 0.73). CONCLUSIONS: Repeat LLR is safe, feasible, and can be
performed with minimal morbidity. It appears to be technically more challenging
than P-LLR, but without any increase in complications or length of hospital stay.
PMID- 25138068
TI - Identification, immunolocalization, and characterization analyses of an
exopeptidase of papain superfamily, (cathepsin C) from Clonorchis sinensis.
AB - Cathepsin C is an important exopeptidase of papain superfamily and plays a number
of great important roles during the parasitic life cycle. The amino acid sequence
of cathepsin C from Clonorchis sinensis (C. sinensis) showed 54, 53, and 49%
identities to that of Schistosoma japonicum, Schistosoma mansoni, and Homo
sapiens, respectively. Phylogenetic analysis utilizing the sequences of papain
superfamily of C. sinensis demonstrated that cathepsin C and cathepsin Bs came
from a common ancestry. Cathepsin C of C. sinensis (Cscathepsin C) was identified
as an excretory/secretory product by Western blot analysis. The results of
transcriptional level and translational level of Cscathepsin C at metacercaria
stage were higher than that at adult worms. Immunolocalization analysis indicated
that Cscathepsin C was specifically distributed in the suckers (oral sucker and
ventral sucker), eggs, vitellarium, intestines, and testis of adult worms. In the
metacercaria, it was mainly detected on the cyst wall and excretory bladder.
Combining with the results mentioned above, it implies that Cscathepsin C may be
an essential proteolytic enzyme for proteins digestion of hosts, nutrition
assimilation, and immune invasion of C. sinensis. Furthermore, it may be a
potential diagnostic antigen and drug target against C. sinensis infection.
PMID- 25138074
TI - Inhibitory effect of plantaricin peptides (Pln E/F and J/K) against Escherichia
coli.
AB - Plantaricins are small bioactive peptides produced by Lactobacillus plantarum
strains that exhibit significant antimicrobial activity against closely-related
Gram-positive bacteria, including food spoilage organisms. In comparison,
bacteriocins including plantaricins, are usually less effective against Gram
negative organisms. In this study, we demonstrate that heterologously expressed
and purified plantaricins, Pln E, -F, -J, and -K when tested against Gram
negative model organism Escherichia coli K-12 were highly effective under certain
conditions. The apparent tolerance of Gram-negative members to these peptides has
been explained on the basis of the presence of the outer membrane (OM) that acts
as a protective barrier. We have shown that agents and/or conditions that
destabilize OM of E. coli K-12, make it susceptible to plantaricin peptides. In
order to further strengthen this conclusion, an OM lipoprotein-defective lpp
mutant strain of E. coli K-12 was also studied and compared. A significant loss
of cell viability both in terms of CFU/ml as well as with live-dead dual staining
combined with flow cytometry, could be demonstrated with the lpp mutant in
comparison to the wild type strain. The results indicate that plantaricins can
inhibit Gram-negative bacteria if the outer-membrane is weakened and it can be
used in preservation of food with the help of some food-grade chelating agents.
PMID- 25138075
TI - A longitudinal study on the impact of active surveillance for prostate cancer on
anxiety and distress levels.
AB - OBJECTIVE: Patients with potentially indolent prostate cancer (PC) can be managed
with active surveillance (AS). Our objective was to analyse how anxiety and
distress develop in men with untreated PC and whether highly anxious men quit AS.
METHODS: One hundred and fifty Dutch patients who opted for AS in the Prostate
cancer Research International: Active Surveillance Study were invited to
participate in an additional prospective, longitudinal quality of life (QoL)
study within 6 months after diagnosis. Participants completed questionnaires with
validated measures on anxiety and distress at inclusion (t = 0), 9 (t = 9) and 18
(t = 18) months after diagnosis. We assessed changes in scores on depression
(Center for Epidemiologic Studies Depression (CES-D) scale), generic anxiety
(State-Trait Anxiety Inventory (STAI-6)), PC-specific anxiety (Memorial Anxiety
Scale for Prostate Cancer (MAX-PC)) and decisional conflict (Decisional Conflict
Scale (DCS)) about patients' treatment choice between t = 0, t = 9 and t = 18
using repeated measures analysis. RESULTS: Response rates for patients still on
AS at t = 0, t = 9 and t = 18 assessments were 86%, 90% and 96%, respectively.
Nine patients (7%, 9/129) between t = 0 and t = 9 and 33 of 108 patients (31%)
between t = 9 and t = 18 stopped AS, mostly (86%) because of protocol-based
reasons. CES-D, total MAX-PC and DCS scores did not change significantly (p >
0.05) when comparing t = 18 with t = 9 and t = 0 scores, but generic anxiety
(STAI-6; p = 0.033) and fear of disease progression (sub-score of the MAX-PC; p =
0.007) decreased significantly. These differences, however, were clinically
modest (0.089 SD and 0.281 SD). Overall, six of 129 men (5%) discontinued AS
because of anxiety and distress. CONCLUSIONS: When men with low-risk PC are
managed with AS, fear of disease progression and general anxiety decreased, and
only few may discontinue AS because of anxiety and distress. This suggests that
negative QoL effects are limited in men with favourable clinical characteristics
who opted for AS. (Registered trial number, NTR1718) .
PMID- 25138076
TI - Proteomic investigation of the hippocampus in prenatally stressed mice implicates
changes in membrane trafficking, cytoskeletal, and metabolic function.
AB - Prenatal stress influences the development of the fetal brain and so contributes
to the risk of the development of psychiatric disorders in later life. The
hippocampus is particularly sensitive to prenatal stress, and robust
abnormalities have been described in the hippocampus in schizophrenia and
depression. The aim of this study was to determine whether prenatal stress is
associated with distinct patterns of differential protein expression in the
hippocampus using a validated mouse model. We therefore performed a comparative
proteomic study assessing female hippocampal samples from 8 prenatally stressed
mice and 8 control mice. Differential protein expression was assessed using 2
dimensional difference in gel electrophoresis and subsequent mass spectrometry.
The observed changes in a selected group of differentially expressed proteins
were confirmed by Western blotting. In comparison to controls, 47 protein spots
(38 individual proteins) were found to be differentially expressed in the
hippocampus of prenatally stressed mice. Functional grouping of these proteins
revealed that prenatal stress influenced the expression of proteins involved in
brain development, cytoskeletal composition, stress response, and energy
metabolism. Western blotting was utilized to validate the changes in calretinin,
hippocalcin, profilin-1 and the signal-transducing adaptor molecule STAM1. Septin
5 could not be validated via Western blotting due to methodological issues.
Closer investigation of the validated proteins also pointed to an interesting
role for membrane trafficking deficits mediated by prenatal stress. Our findings
demonstrate that prenatal stress leads to altered hippocampal protein expression,
implicating numerous molecular pathways that may provide new targets for
psychotropic drug development.
PMID- 25138077
TI - Diffraction interference induced superfocusing in nonlinear Talbot effect.
AB - We report a simple, novel subdiffraction method, i.e. diffraction interference
induced superfocusing in second-harmonic (SH) Talbot effect, to achieve focusing
size of less than lambdaSH/4 (or lambdapump/8) without involving evanescent waves
or subwavelength apertures. By tailoring point spread functions with Fresnel
diffraction interference, we observe periodic SH subdiffracted spots over a
hundred of micrometers away from the sample. Our demonstration is the first
experimental realization of the Toraldo di Francia's proposal pioneered 62 years
ago for superresolution imaging.
PMID- 25138078
TI - Use of prophylactic postoperative antibiotics during surgical drain presence
following mastectomy.
AB - BACKGROUND: National guidelines recommend one dose of perioperative antibiotics
for breast surgery and discourage postoperative continuation. However, reported
skin and soft tissue infection (SSI) rates after mastectomy range from 1-26 %,
higher than expected for clean cases. Utility of routine or selective
postoperative antibiotic use for duration of drain presence following mastectomy
remains uncertain. METHODS: This study included all female patients who underwent
mastectomy without reconstruction at our institution between 2005 and 2012. SSI
was defined using CDC criteria or clinical diagnosis of cellulitis. Information
on risk factors for infection (age, body mass index [BMI], smoking status,
diabetes, steroid use), prior breast cancer treatment, drain duration, and
antibiotic use was abstracted from medical records. Multivariable logistic
regression was used to assess the association between postoperative antibiotic
use and the occurrence of SSI, adjusting for concurrent risk factors. RESULTS:
Among 480 patients undergoing mastectomy without reconstruction, 425 had
sufficient documentation for analysis. Of these, 268 were prescribed antibiotics
(63 %) at hospital discharge. An overall SSI rate of 7.3 % was observed, with 14
% of patients without postoperative antibiotics developing SSI compared with 3.4
% with antibiotics (p < 0.0001). Factors independently associated with SSI were
smoking and advancing age. Diabetes, steroid use, BMI, prior breast surgery,
neoadjuvant chemotherapy, prior radiation, concomitant axillary surgery, and
drain duration were not associated with increased SSI rates. CONCLUSIONS: SSI
rates among patients who did and did not receive postoperative antibiotics after
mastectomy were significantly different, particularly among smokers and women of
advanced age. These patient subgroups may warrant special consideration for
postoperative antibiotics.
PMID- 25138079
TI - Intraoperative radiation therapy: a critical analysis of the ELIOT and TARGIT
trials. Part 2--TARGIT.
AB - BACKGROUND: Two randomized intraoperative radiation therapy trials for early
stage breast cancer were recently published. The ELIOT Trial used electrons
(IOERT), and the TARGIT-A Trial Update used 50-kV X-rays (IORT). These studies
were compared for similarities and differences. The results were analyzed and
used to determine which patients might be suitable for single-dose treatment.
METHODS: The primary sources of data were the ELIOT Trial and TARGIT-A Trial, as
well as a comprehensive analysis of the peer-reviewed literature of accelerated
partial breast irradiation (APBI) using 50-kV X-rays or electrons. Studies
published or presented prior to March 2014 were analyzed for efficacy, patient
restrictions, complications, and outcome. RESULTS: With a median follow-up of 5.8
years, the 5-year recurrence rates for ELIOT versus EBRT patients were 4.4 and
0.4 %, respectively, p = 0.0001. A low-risk ELIOT group was identified with a 5
year recurrence rate of 1.5 %. With a median follow-up of 29 months, the 5-year
recurrence rates for the TARGIT-A versus EBRT patients were 3.3 and 1.3 %,
respectively, p = 0.042. CONCLUSIONS: With 5.8 years of median follow-up, IOERT
appears to have a subset of low risk women for whom IOERT is acceptable. With 29
months of median follow-up the results of IORT with 50-kV devices are promising,
but longer follow-up data are required. At the current time, single-fraction
IOERT or IORT patients should be treated under strict institutional protocols.
PMID- 25138080
TI - Exploring barriers to payer utilization of genetic counselors.
AB - Access to genetic counselors' services is neither universal nor automatic, due in
part to the gatekeeper role of healthcare payers--the companies and agencies that
purchase healthcare services on patients' behalf and control the bulk of
healthcare spending. This pilot study surveyed and analyzed the relative
importance of barriers to expanded payer coverage of genetic counselors'
services. Surveys were mailed to 263 medical directors and quality assurance
directors at health insurance carriers throughout the United States. Respondents
provided demographic information and indicated the importance of nine possible
barriers, plus an optional write-in "other." Twenty-two surveys were analyzed.
"Evidence that use of genetic counselors improves health outcomes" led the list
of factors having a significant/very significant influence on coverage policy.
Sixteen respondents (73 %) rated this factor "4" or "5" on a Likert scale; it
also received the most #1 rankings and the highest score using a weighted-mean
analysis. Provider practice guidelines, CMS/Medicare regulations, and genetic
counselor licensure-all of which are outside of payers' direct control-also
ranked highly. The research demonstrates that although the potential barriers to
expanded reimbursement for genetic counselors are numerous and complex, some are
more consistently identified as important and therefore more deserving of
legislative and advocacy resources to effect change. Future research should
endeavor to increase survey response and include providers as well as payers.
PMID- 25138081
TI - The utilization of counseling skills by the laboratory genetic counselor.
AB - The number of available genetic testing options and the nuances associated with
these options continue to expand. In addition, the scope of genetic testing has
broadened to areas and specialties beyond Medical Genetics. In response to these
changes, diagnostic laboratories have employed genetic counselors to help
navigate the increasing complexity of genetic testing, given their expertise and
training in human genetics. However a largely unrecognized aspect of this role
involves the use of counseling skills. Counseling skills are used by laboratory
genetic counselors in a variety of situations to convey information and
facilitate understanding among clinicians and medical staff. This helps to reduce
test ordering errors, promote optimal test utilization, and ensure best patient
care practices. The specific counseling skills used by laboratory counselors will
be explored using three fictional case vignettes, followed by a discussion of the
applicability of these skills in other contexts. Exploration of the unique ways
in which laboratory genetic counselors apply their counseling skills can be
useful for professional development and instructive for graduate training
programs.
PMID- 25138083
TI - The clash of mechanical and electrical size-effects in ZnO nanowires and a double
power law approach to elastic strain engineering of piezoelectric and piezotronic
devices.
AB - The piezoelectric performance of ultra-strength ZnO nanowires (NWs) depends on
the subtle interplay between electrical and mechanical size-effects. "Size
dependent" modeling of compressed NWs illustrates why experimentally observed
mechanical stiffening can indeed collide with electrical size-effects when the
size shrinks, thereby lowering the actual piezoelectric function from bulk
estimates. "Smaller" is not necessarily "better" in nanotechnology.
PMID- 25138082
TI - Chiral amine synthesis using omega-transaminases: an amine donor that displaces
equilibria and enables high-throughput screening.
AB - The widespread application of omega-transaminases as biocatalysts for chiral
amine synthesis has been hampered by fundamental challenges, including
unfavorable equilibrium positions and product inhibition. Herein, an efficient
process that allows reactions to proceed in high conversion in the absence of by
product removal using only one equivalent of a diamine donor (ortho
xylylenediamine) is reported. This operationally simple method is compatible with
the most widely used (R)- and (S)-selective omega-TAs and is particularly
suitable for the conversion of substrates with unfavorable equilibrium positions
(e.g., 1-indanone). Significantly, spontaneous polymerization of the isoindole by
product generates colored derivatives, providing a high-throughput screening
platform to identify desired omega-TA activity.
PMID- 25138084
TI - The development of ataxia telangiectasia mutated kinase inhibitors.
AB - Radiation and genotoxic drugs are two of the cornerstones of current cancer
treatment strategy. However, this type of therapy often suffers from radio- or
chemo-resistance caused by DNA repair mechanisms. With the aim of increasing the
efficacy of these treatments, there has been great interest in studying DNA
damage responses (DDR). Among the plethora of signal and effector proteins
involved in DDR, three related kinases ATM (ataxia telangiectasia mutated), ATR
(ATM and Rad3-related) and DNA-PK (DNA-dependent protein kinase) play the main
roles in initiation and regulation of signaling pathways in response to DNA
double and single strand breaks (DSB and SSB). ATM inhibitors, as well as those
of ATR and DNA-PK, provide an opportunity to sensitize cancer cells to therapy.
Moreover, they can lead to selective killing of cancer cells, exploiting a
concept known as synthetic lethality. However, only a very few selective
inhibitors have been identified to this date. This mini-review is focused both on
the development of selective inhibitors of ATM and other inhibitors which have
ATM as one of their targets.
PMID- 25138085
TI - Xanthomicrol: a comprehensive review of its chemistry, distribution, biosynthesis
and pharmacological activity.
AB - Highly methoxylated flavones, which have known potential as cancer
chemopreventive agents, accumulate on the leaf surfaces of some plant species and
their physiological role is to protect the plant against harmful UV radiation.
Xanthomicrol is one of the methoxylated flavones currently attracting most
attention from researchers worldwide because of its promising pharmacological
activities, including anti-spasmodic, anti-platelet and anti-cancer effects,
among others. This review covers the chemistry and biological origin,
distribution and pharmacological activity of xanthomicrol. Knowledge of the
botanical distribution of this compound will not only encourage the use of plant
sources for pharmacological purposes, but will also serve as a reference in the
search for this valuable flavonoid in another genus or family. New approaches to
xanthomicrol production are also described, including biotechnological attempts
to develop xanthomicrol-producing plant cell factories.
PMID- 25138086
TI - The toolbox of designing nanoparticles for tumors.
AB - Nanoparticles (NPs) show great promise in the treatment of a wide range of
diseases, which provides advantages and offers a new prospect for tumor
detection, prevention and treatment. In order to eradicate the cancer cell, the
NPs need to flow to different regions of tumors via blood vessels, and then
penetrate through the interstitial space to reach the target cells. However, the
environment and physiological characteristics in tumor tissues are different from
that in normal ones, mainly in the irregular blood vessels, the lack of lymphatic
network, low pH, hypoxia, immune function and so on. Meanwhile, the differences
also exist among different tumor tissues. To achieve the optimal therapeutic
effect, the NPs should be carefully designed by considering the therapeutic
application, the target site and the route of administration. This review shows a
variety of barriers in the tumor tissues, and provides a toolbox of designing the
NPs for tumor treatment. In particular, the particle size, shape and surface
chemistry, and the NPs in preclinical and clinical stage use have been discussed.
PMID- 25138087
TI - Sea, carbohydrates and clotting: a triad on the road of drug discovery.
AB - Cardiovascular diseases (CDs) are the principal cause of death in the world.
Anticoagulation is the commonest therapeutic strategy for treatments of CDs in
clinical settings. Although possessed of numerous downsides, heparin is the main
clinical anticoagulant/antithrombotic agent used so far. Novel sulfated
polysaccharides like the marine dermatan sulfate, sulfated fucans and galactans
are also able to block clot and thrombus formation. These relatively new marine
glycans call special attention mostly due to their unique structures and distinct
mechanisms of action. This structural uniqueness is seen by the peculiar aspect
of these polysaccharides being made of clear and regular sulfation patterns. The
structures have been reported only in polysaccharides from marine invertebrates
like sea urchins and cucumbers. This report intends to prove the promising
combination of the triad sea-carbohydrates-clotting in drug discovery of the
cardiovascular field.
PMID- 25138088
TI - Benzimidazoles: an ideal privileged drug scaffold for the design of multitargeted
anti-inflammatory ligands.
AB - The recent research area endeavors to discover ultimate multi-target ligands, an
increasingly feasible and attractive alternative to existing mono-targeted drugs
for treatment of complex, multi-factorial inflammation process which underlays
plethora of debilitated health conditions. In order to improvise this option,
exploration of relevant chemical core scaffold will be an utmost need. Privileged
benzimidazole scaffold being historically versatile structural motif could offer
a viable starting point in the search for novel multi-target ligands against
multi-factorial inflammation process since, when appropriately substituted, it
can selectively modulate diverse receptors, pathways and enzymes associated with
the pathogenesis of inflammation. Despite this remarkable capability, the multi
target capacity of the benzimidazole scaffold remains largely unexploited. With
this in focus, the present review article attempts to provide synopsis of
published research to exemplify the valuable use of benzimidazole nucleus and
focus on their suitability as starting scaffold to develop multi-targeted anti
inflammatory ligands.
PMID- 25138089
TI - Drug targeting systems for cancer therapy: nanotechnological approach.
AB - Progress in cancer treatment remains challenging because of the great nature of
tumor cells to be drug resistant. However, advances in the field of
nanotechnology have enabled the delivery of drugs for cancer treatment by
passively and actively targeting to tumor cells with nanoparticles. Dramatic
improvements in nanotherapeutics, as applied to cancer, have rapidly accelerated
clinical investigations. In this review, drug-targeting systems using
nanotechnology and approved and clinically investigated nanoparticles for cancer
therapy are discussed. In addition, the rationale for a nanotechnological
approach to cancer therapy is emphasized because of its promising advances in the
treatment of cancer patients.
PMID- 25138090
TI - An overview of conjugated linoleic acid: microbial production and application.
AB - Conjugated linoleic acid (CLA) has attracted considerable attention in health due
to its important physiological properties proved in several in vivo experiments.
Many bacteria, especially some probiotics, are able to produce CLA from the
linoleic acid (LA) present in milk. In this review, CLA production by
microorganisms is described. Then factors on the influencing the microbial
production and the initial CLA content in milk fat are introduced. After a
glimpse on the content of CLA in dairy products and human body, health benefits
of CLA including anti-cancer, anti-diabetic, antiathrosclerosis and anti
osteoporosis properties, as well as prevention of body fat increase and function
as stimulator of the immunity system are explained.
PMID- 25138091
TI - Natural products; pharmacological importance of family Cucurbitaceae: a brief
review.
AB - Compounds derived from nature have played a major role in drug discovery. They
became the basis for the development of new pharmaceuticals. In this scope,
family Cucurbitaceae is a prominent source of secondary metabolites, mainly
triterpenoids. In this paper, we provide a brief review of cucurbitane
metabolites that exhibit an extensive range of biological actions specifically
antidiabetic, anti-inflammatory, cytotoxic, hepatoprotective, and antiparasitic
effects.
PMID- 25138092
TI - Enoyl ACP reductase as effective target for the synthesized novel antitubercular
drugs: a-state-of-the-art.
AB - The emergence of drug resistant strains of important human pathogens has created
an urgent necessity to find new targets and novel antitubercular agents.
According to the literature survey, we noticed that enoyl ACP reductase is one of
the most promising targets. This enzyme is the most important catalyst for the
FAS II synthesis of mycolic acid, which is the most essential component of the
mycobacterial cell wall. This review summarizes the progress made in the design
of enoyl ACP reductase inhibitors and the role played by 3D-structure of the
enzyme in drug design process.
PMID- 25138093
TI - Occurrence and biological activities of eremophilane-type sesquiterpenes.
AB - As important members of the terpenes family, sesquiterpenes represent a group of
natural compounds with diverse skeletal types. Among them, the eremophilane-type
sesquiterpenes, widely present in several genera (such as Ligularia, Senecio,
Cacalia) of Asteraceae, account for a small number of natural compounds and form
differently from other sesquiterpenes because they challenged the isoprene rule
of biosynthesis. Due to the unique structural features and various functional
groups, these compounds possess a number of biological activities such as anti
tumor, anti-bacterial and anti-inflammatory, having received increasing interest
in the recent years. This review summarizes the occurrence of eremophilane-type
sesquiterpenes and research progresses on their biological activities since the
1990 s.
PMID- 25138094
TI - Combined cancer therapy with non-conventional drugs: all roads lead to AMPK.
AB - AMP-activated protein kinase (AMPK) is a key energy sensor that regulates
cellular energy homeostasis. AMPK activation is associated with decreased
phosphorylation of mammalian target of rapamycin (mTOR) and S6 kinase and causes
a general reduction in mRNA translation and protein synthesis. Therefore, AMPK is
a novel target for anticancer therapy. Metformin and aspirin are two traditional
drugs that are widely used as anti-diabetes and non-steroidal anti-inflammatory
drugs (NSAIDs), respectively. Much evidence has confirmed that these two drugs
demonstrated encouraging anti-cancer properties. Most importantly, both inhibited
tumor proliferation and were mainly dependent on the AMPK/mTOR signaling pathway.
In addition, several other drugs, such as resveratrol, berberine, statins,
epigallocatechin gallate (EGCG) and capsaicin, have provided a similar capacity
for tumor inhibition, and the anti-cancer effects of most of them were mainly the
result of AMPK activation. In the current review, we summarize the literature on
combination therapy based on these non-classical drugs and their potential
mechanisms for activating AMPK. Combinations of these drugs will provide a novel
cancer therapeutic regimen.
PMID- 25138095
TI - Identification of a pathogenic variant in TREX1 in early-onset cerebral systemic
lupus erythematosus by Whole-exome sequencing.
AB - Objective. Systemic lupus erythematosus (SLE) isa chronic and heterogeneous
autoimmune disease. Both twin and sibling studies indicate a strong genetic
contribution to lupus, but in the majority of cases the pathogenic variant
remains to be identified. The genetic contribution to disease is likely to be
greatest in cases with early onset and severe phenotypes. Whole-exome sequencing
now offers the possibility of identifying rare alleles responsible for disease in
such cases. This study was undertaken to identify genetic causes of SLE using
whole-exome sequencing.Methods. We performed whole-exome sequencing in a 4-year
old girl with early-onset SLE and conducted biochemical analysis of the putative
defect.Results. Whole-exome sequencing in a 4-year-old girl with cerebral lupus
identified a rare, homozygous mutation in the three prime repair exonuclease 1
gene(TREX1) that was predicted to be highly deleterious.The TREX1 R97H mutant
protein had a 20-fold reduction in exonuclease activity and was associated with
an elevated interferon-alpha signature in the patient.The discovery and
characterization of a pathogenic TREX1 variant in our proband has therapeutic
implications.The patient is now a candidate for therapy. Conclusion. Our study is
the first to demonstrate that whole-exome sequencing can be used to identify rare
or novel deleterious variants as genetic causes of SLE and, through a
personalized approach, improve therapeutic options.
PMID- 25138096
TI - Dr. Richard Fitzpatrick July 21, 1944-July 12, 2014.
PMID- 25138097
TI - An automatic robotic system for three-dimensional tooth crown preparation using a
picosecond laser.
AB - BACKGROUND: Laser techniques have been introduced into dentistry to overcome the
drawbacks of traditional treatment methods. The existing methods in dental
clinical operations for tooth crown preparation have several drawbacks which
affect the long-term success of the dental treatment. OBJECTIVE: To develop an
improved robotic system to manipulate the laser beam to achieve safe and accurate
three-dimensional (3D) tooth ablation, and thus to realize automatic tooth crown
preparation in clinical operations. METHOD: We present an automatic laser
ablation system for tooth crown preparation in dental restorative operations. The
system, combining robotics and laser technology, is developed to control the
laser focus in three-dimensional motion aiming for high speed and accuracy crown
preparation. The system consists of an end-effector, a real-time monitor and a
tooth fixture. A layer-by-layer ablation method is developed to control the laser
focus during the crown preparation. Experiments are carried out with picosecond
laser on wax resin and teeth. RESULTS: The accuracy of the system is satisfying,
achieving the average linear errors of 0.06 mm for wax resin and 0.05 mm for
dentin. The angle errors are 4.33 degrees for wax resin and 0.5 degrees for
dentin. The depth errors for wax resin and dentin are both within 0.1 mm. The
ablation time is 1.5 hours for wax resin and 3.5 hours for dentin. CONCLUSIONS:
The ablation experimental results show that the movement range and the resolution
of the robotic system can meet the requirements of typical dental operations for
tooth crown preparation. Also, the errors of tooth shape and preparation angle
are able to satisfy the requirements of clinical crown preparation. Although the
experimental results illustrate the potential of using picosecond lasers for 3D
tooth crown preparation, many research issues still need to be studied before the
system can be applied to clinical operations.
PMID- 25138099
TI - Loss-of-function variants of SETD5 cause intellectual disability and the core
phenotype of microdeletion 3p25.3 syndrome.
AB - Intellectual disability (ID) has an estimated prevalence of 2-3%. Due to its
extreme heterogeneity, the genetic basis of ID remains elusive in many cases.
Recently, whole exome sequencing (WES) studies revealed that a large proportion
of sporadic cases are caused by de novo gene variants. To identify further genes
involved in ID, we performed WES in 250 patients with unexplained ID and their
unaffected parents and included exomes of 51 previously sequenced child-parents
trios in the analysis. Exome analysis revealed de novo intragenic variants in SET
domain-containing 5 (SETD5) in two patients. One patient carried a nonsense
variant, and the other an 81 bp deletion located across a splice-donor site.
Chromosomal microarray diagnostics further identified four de novo non-recurrent
microdeletions encompassing SETD5. CRISPR/Cas9 mutation modelling of the two
intragenic variants demonstrated nonsense-mediated decay of the resulting
transcripts, pointing to a loss-of-function (LoF) and haploinsufficiency as the
common disease-causing mechanism of intragenic SETD5 sequence variants and SETD5
containing microdeletions. In silico domain prediction of SETD5, a predicted SET
domain-containing histone methyltransferase (HMT), substantiated the presence of
a SET domain and identified a novel putative PHD domain, strengthening a
functional link to well-known histone-modifying ID genes. All six patients
presented with ID and certain facial dysmorphisms, suggesting that SETD5 sequence
variants contribute substantially to the microdeletion 3p25.3 phenotype. The
present report of two SETD5 LoF variants in 301 patients demonstrates a
prevalence of 0.7% and thus SETD5 variants as a relatively frequent cause of ID.
PMID- 25138101
TI - Evaluation of the Dutch BRCA1/2 clinical genetic center referral criteria in an
unselected early breast cancer population.
AB - In this study, we evaluated the diagnostic value of the Dutch Clinical Genetic
Center (CGC) referral guidelines for BRCA1/2 mutation testing in 903 early breast
cancer patients, unselected for family history, diagnosed in a cancer hospital
before the age of 50 years in 1974-2002; most prevalent Dutch pathogenic BRCA1/2
mutations had been analyzed on coded DNA in a research setting. Forty-nine (5.4%)
of the patients were proven to be BRCA1/2 mutation carriers. We found that 78%
and 69% of BRCA1 and BRCA2 mutation carriers identified met the criteria for
referral to the CGC based on age, family history and synchronous multiple tumors;
reflected by a combined sensitivity of 75.5% and specificity of 63.2%. More than
half of the BRCA1 mutation carriers, that is, 58% had a triple-negative tumor.
The highest AUC was obtained by shifting the age at diagnosis threshold criterion
from 40 to 35 years and by adding a 'triple-negative breast cancer' criterion
with an age threshold of 45 years; the specificity increased to 71.2%, whereas
the sensitivity remained the same; that is, a referral of fewer patients will
lead to the identification of at least the same number of BRCA1/2 mutation
carriers. Two-thirds of the BRCA1/2 mutation carriers identified in this research
setting had been referred for counseling and testing. Our results indicate that,
awaiting a possibly more extended mutation screening of all breast cancer
patients, the triple-negative status of a breast cancer should be added to the
CGC referral criteria.
PMID- 25138100
TI - Identification of a novel ARL13B variant in a Joubert syndrome-affected patient
with retinal impairment and obesity.
AB - Joubert syndrome (JS) is a genetically heterogeneous autosomal recessive
ciliopathy with 22 genes implicated to date, including a small, ciliary GTPase,
ARL13B. ARL13B is required for cilia formation in vertebrates. JS patients
display multiple symptoms characterized by ataxia due to the cerebellar vermis
hypoplasia, and that can also include ocular abnormalities, renal cysts, liver
fibrosis or polydactyly. These symptoms are shared with other ciliopathies, some
of which display additional phenotypes, such as obesity. Here we identified a
novel homozygous missense variant in ARL13B/JBTS8 in a JS patient who displayed
retinal defects and obesity. We demonstrate the variant disrupts ARL13B function,
as its expression did not rescue the mutant phenotype either in Arl13b(scorpion)
zebrafish or in Arl13b(hennin) mouse embryonic fibroblasts, while the wild-type
ARL13B did. Finally, we show that ARL13B is localized within the primary cilia of
neonatal mouse hypothalamic neurons consistent with the known link between
hypothalamic ciliary function and obesity. Thus our data identify a novel ARL13B
variant that causes JS and retinopathy and suggest an extension of the phenotypic
spectrum of ARL13B mutations to obesity.
PMID- 25138102
TI - A missense variant of the ATP1A2 gene is associated with a novel phenotype of
progressive sensorineural hearing loss associated with migraine.
AB - Hereditary sensorineural hearing loss is an extremely clinical and genetic
heterogeneous disorder in humans. Especially, syndromic hearing loss is
subdivided by combinations of various phenotypes, and each subtype is related to
different genes. We present a new form of progressive hearing loss with migraine
found to be associated with a variant in the ATP1A2 gene. The ATP1A2 gene has
been reported as the major genetic cause of familial migraine by several previous
studies. A Korean family presenting progressive hearing loss with migraine was
ascertained. The affected members did not show any aura or other neurologic
symptoms during migraine attacks, indicating on a novel phenotype of syndromic
hearing loss. To identify the causative gene, linkage analysis and whole-exome
sequencing were performed. A novel missense variant, c.571G>A (p.(Val191Met)),
was identified in the ATP1A2 gene that showed co-segregation with the phenotype
in the family. In silico studies suggest that this variant causes a change in
hydrophobic interactions and thereby slightly destabilize the A-domain of
Na(+)/K(+)-ATPase. However, functional studies failed to show any effect of the
p.(Val191Met) substitution on the catalytic rate of this enzyme. We describe a
new phenotype of progressive hearing loss with migraine associated with a variant
in the ATP1A2 gene. This study suggests that a variant in Na(+)/K(+)-ATPase can
be involved in both migraine and hearing loss.
PMID- 25138103
TI - Orange alert.
PMID- 25138105
TI - Misclassification due to age grouping in measures of child development.
AB - PURPOSE: Screens for developmental delay generally provide a set of norms for
different age groups. Development varies continuously with age, however, and
applying a single criterion for an age range will inevitably produce
misclassifications. In this report, we estimate the resulting error rate for one
example: the cognitive subscale of the Bayley Scales of Infant and Toddler
Development (BSID-III). DESIGN: Data come from a general population sample of 594
children (305 male) aged 1 month to 42.5 months who received the BSID-III as part
of a validation study. We used regression models to estimate the mean and
variance of the cognitive subscale as a function of age. We then used these
results to generate a dataset of one million simulated participants and compared
their status before and after division into age groups. Finally, we applied
broader age bands used in two other instruments and explored likely validity
limitations when different instruments are compared. RESULTS: When BSID-III age
groups are used, 15% of cases are missed and 15% of apparent cases are false
positives. Wider age groups produced error rates from 27% to 46%. Comparison of
different age groups suggests that sensitivity in validation studies would be
limited, under certain assumptions, to 70% or less. IMPLICATIONS: The use of age
groups produces a large number of misclassifications. Although affected children
will usually be close to the threshold, this may lead to misreferrals. Results
may help to explain the poor measured agreement of development screens. Scoring
methods that treat child age as continuous would improve instrument accuracy.
PMID- 25138104
TI - Assessment of neonatal care in clinical training facilities in Kenya.
AB - OBJECTIVE: An audit of neonatal care services provided by clinical training
centres was undertaken to identify areas requiring improvement as part of wider
efforts to improve newborn survival in Kenya. DESIGN: Cross-sectional study using
indicators based on prior work in Kenya. Statistical analyses were descriptive
with adjustment for clustering of data. SETTING: Neonatal units of 22 public
hospitals. PATIENTS: Neonates aged <7 days. MAIN OUTCOME MEASURES: Quality of
care was assessed in terms of availability of basic resources (principally
equipment and drugs) and audit of case records for documentation of patient
assessment and treatment at admission. RESULTS: All hospitals had oxygen, 19/22
had resuscitation and phototherapy equipment, but some key resources were missing
for example kangaroo care was available in 14/22. Out of 1249 records, 56.9% (95%
CI 36.2% to 77.6%) had a standard neonatal admission form. A median score of 0
out of 3 for symptoms of severe illness (IQR 0-3) and a median score of 6 out of
8 for signs of severe illness (IQR 4-7) were documented. Maternal HIV status was
documented in 674/1249 (54%, 95% CI 41.9% to 66.1%) cases. Drug doses exceeded
recommendations by >20% in prescriptions for penicillin (11.6%, 95% CI 3.4% to
32.8%) and gentamicin (18.5%, 95% CI 13.4% to 25%), respectively. CONCLUSIONS:
Basic resources are generally available, but there are deficiencies in key areas.
Poor documentation limits the use of routine data for quality improvement.
Significant opportunities exist for improvement in service delivery and adherence
to guidelines in hospitals providing professional training.
PMID- 25138107
TI - A review of pre-admission advanced airway management in combat casualties,
Helmand Province 2013.
AB - OBJECTIVES: Airway compromise is the third leading cause of potentially
preventable combat death. Pre-hospital airway management has lower success rates
than in hospital. This study reviewed advanced airway management focusing on
cricothyroidotomies and supraglottic airway devices in combat casualties prior to
admission to a Role 3 Hospital in Afghanistan. METHODS: This was a retrospective
review of all casualties who required advanced airway management prior to arrival
at the Role 3 Hospital, Bastion, Helmand Province over a 30-week period
identified by the US Joint Theatre Trauma Registry. The notes and relevant X-rays
were analysed. The opinions of US and UK clinical Subject Matter Experts (SME)
were then sought. RESULTS: Fifty-seven advanced airway interventions were
identified. 45 casualties had attempted intubations, 37 (82%) were successful and
of those who had failed intubations, one had a King LT Airway (supraglottic
device) and seven had a rescue cricothyroidotomy. The other initial advanced
airway interventions were five attempted King LT airways and seven attempted
cricothyroidotomies. In total, 14 cricothyroidotomies were performed; in this
group, there were nine complications/significant events. CONCLUSIONS: The SMEs
suggested that dedicated surgical airway kits should be used and students in
training should be taught to secure the cricothyroidotomy tube as well as how to
insert it. This review re-emphasises the need to 'ensure the right person, with
the right equipment and the right training, is present at the right time if we
are to improve the survival of patients with airway compromise on the
battlefield'. The audit reference number is RCDM/Res/Audit/1036/12/0368.
PMID- 25138106
TI - Changes in sleep characteristics and airway obstruction in OSAHS patients with
multi-level obstruction following simple UPPP, UPPP-GA, or UPPP-TBA: a
prospective, single-center, parallel group study.
AB - OBJECTIVE: To investigate changes in S3 sleep and the apnea hypopnea index (AHI),
SpO2 desaturation and CT90, and to determine changes in the degree of airway
collapse and in the cross-sectional area of the retropalatal and lingual region
in obstructive sleep apnea hypopnea syndrome patients. METHOD: All subjects
underwent overnight polysomnography and were evaluated using Muller's test and
magnetic resonance imaging at baseline, 3, and 12 months following surgery.
RESULT: The mean S3 scores in patients receiving uvulopalatopharyngoplasty
combined with genioglossus advancement (UPPP-GA) or UPPP combined with tongue
base advancement using the ReposeTM system (UPPP-TBA) noticeably increased.
Marked improvement was seen in the mean AHI, LSO2, and CT90 scores 3 and 12
months following surgery compared to baseline. Airway collapsed by 25-50% in the
greatest proportion undergoing surgery at the tongue base. CONCLUSION: UPPP-GA
and UPPP-TBA more effectively improve S3 sleep, and mean AHI, LSO2, and CT90
scores. In addition, they effectively alleviate airway obstruction by improving
the cross-sectional area of these regions.
PMID- 25138108
TI - Cardiovascular disease and cancer compete for the outcome of death.
PMID- 25138109
TI - Does a single session of high-intensity interval training provoke a transient
elevated risk of falling in seniors and adults?
AB - BACKGROUND: Balance and strength training can reduce seniors' fall risk up to
50%. Available evidence suggests that acute bouts of neuromuscular and endurance
exercise deteriorate postural control. High-intensity endurance training has been
successfully applied in different populations. Thus, it seemed valuable to
examine the acute effects of high-intensity interval training (HIIT) on
neuromuscular performance in seniors and young adults. OBJECTIVE: The acute
impact of a HIIT session on balance performance and muscle activity after
exercise cessation and during post-exercise recovery was examined in young and
old adults. We intended to investigate whether a transient exercise-induced fall
risk may occur in both groups. METHODS: 20 healthy seniors (age 70 (SD 4) years)
and young adults (age 27 (SD 3) years) were examined on 3 days. After exhaustive
ramp-like treadmill testing in order to determine maximal heart rate (HRmax) on
the first day, either a 4 * 4 min HIIT at 90% of HRmax or a control condition
(CON) was randomly performed on the second and third day, respectively. Balance
performance (postural sway) was assessed during single limb stance with open eyes
(SLEO) and double limb stance with closed eyes (DLEC). EMG was recorded for the
soleus (SOL), anterior tibialis (TIB), gastrocnemius (GM) and peroneus longus
(PL) muscles at the dominant leg. All measures were collected before, immediately
as well as 10, 30 and 45 min after HIIT and CON, respectively. RESULTS: Compared
to CON, HIIT induced significant increases of postural sway immediately after
exercise cessation during SLEO in both groups (adults: p < 0.001, Delta = +25%
sway; seniors: p = 0.007, Delta = +15% sway). Increased sway during DLEC was only
found for seniors immediately and 10 min after HIIT (post: p = 0.003, Delta =
+14% sway, 10 min post: p = 0.004, Delta = +18% sway). Muscle activity was
increased during SLEO for TIB until 10 min post in seniors (0.008 < p < 0.03) and
immediately after HIIT in adults (p < 0.001). CONCLUSION: HIIT training may cause
an acute 'open-fall-window' with a transient impairment of balance performance
for at least 10 min after exercise cessation in both groups. Occluded vision in
seniors seems to prolong this period up to 30 min. Thus, the advantage of HIIT
with regard to time efficiency seems debatable when considering transient HIIT
induced impairments of neuromuscular function.
PMID- 25138110
TI - Treatment of pegylated interferon-alpha2a in chronic hepatitis B patients
demonstrating a spontaneous decline in HBV DNA after acute exacerbation.
AB - BACKGROUND: Acute exacerbation (AE) in chronic hepatitis B (CHB) is usually
followed by a spontaneous decline in HBV DNA levels. The subsequent treatment is
controversial. In this study, we evaluated the efficacy and safety of pegylated
interferon-alpha2a (PEG-IFN-alpha2a) for such CHB patients. METHODS: A total of
74 hepatitis B e antigen (HBeAg)-positive patients with a spontaneous HBV DNA
decline (by >2 log10 IU*ml(-1), compared with baseline levels before antiviral
treatment) after AE (alanine aminotransferase [ALT]: 10-30-fold the upper limit
of normal [ULN], total bilirubin [TBIL]: 2-20 mg*dl(-1), prothrombin time
activity >60%) were included. In total, 22 patients (group A) received PEG-IFN
alpha2a treatment (180 ug*kg(-1)*week(-1), when ALT was <10 ULN and TBIL<2 mg*dl(
1)) for 48 weeks, with 48 weeks of treatment-free follow-up. Twenty-one patients
(group B) selected continual entecavir therapy. Thirty-one patients (group C,
control group) received routine liver-protective drugs. RESULTS: At week 96,
virological response rates were 90.5%, 100% and 48%, and ALT normalization rates
were 81%, 95% and 40% for groups A, B and C, respectively. HBeAg seroconversion
rates were 71.4%, 45% and 32% in groups A, B and C, respectively. A high
hepatitis B surface antigen (HBsAg) loss rate was observed in PEG-IFN-alpha2a
treated patients, while no entecavir-treated patients achieved HBsAg loss. Group
A patients suffered from typical PEG-IFN therapy-related adverse events. No
severe adverse event was observed in any groups. CONCLUSIONS: PEG-IFN-alpha2a is
effective and safe for treating CHB patients demonstrating a spontaneous decline
in HBV DNA after AE, and yields an increased likelihood of HBsAg loss.
PMID- 25138112
TI - Israeli Society of Medical Genetics NIPT Committee Opinion 072013: Non-invasive
prenatal testing of cell-free DNA in maternal plasma for detection of fetal
aneuploidy.
AB - Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal plasma is
a novel approach, designed for detecting common aneuploidies in the fetus. The
Israeli Society of Medical Geneticists (ISMG) supports its use according to the
guidelines stated herein. The clinical data collected thus far indicate that NIPT
is highly sensitive in detecting trisomies 21 and 18, and fairly sensitive in
detecting trisomy 13 and sex chromosome aneuploidies. Because false-positive
results may occur, an abnormal result must be validated by invasive prenatal
testing. At this juncture, NIPT does not replace existing prenatal screening
tests for Down syndrome, as these are relatively inexpensive and cost-effective.
Nonetheless, NIPT may be offered to women considered to be at high risk for fetal
chromosomal abnormalities as early as 10 weeks of gestation. The ISMG states that
NIPT should be an informed patient choice, and that pretest counseling regarding
the limitations of NIPT is warranted. Women at high risk for genetic disorders
not detected by NIPT should be referred for genetic counseling. A normal test
result may be conveyed by a relevant healthcare provider, while an abnormal
result should be discussed during a formal genetic consultation session.
PMID- 25138111
TI - Fear of movement/(Re)injury in low back pain: confirmatory validation of a German
version of the Tampa Scale for Kinesiophobia.
AB - BACKGROUND: The Tampa Scale for Kinesiophobia (TSK), an instrument for measuring
fear of movement/(re)injury, has been confirmed as an important predictor for the
persistence of pain-related disability. The aims of this study were to evaluate
the psychometric properties of a German version of the TSK (TSK-GV), examining
aspects of content validity with special focus on fear-avoidance and endurance,
and to confirm criterion-related validity in patients with low back pain (LBP).
METHODS: A total of 191 patients with LBP were included in this study. Several
models with different factor structures from published studies were compared in a
confirmatory factor analysis. Internal consistencies of the TSK-GV and its
subscales were examined, and correlations with related self-report measures were
calculated. RESULTS: The internal consistency of the TSK-GV was alpha = 0.73. A
two-factor model with 11 items was found to be the best fit for our data. The two
factors were labelled Somatic Focus (SF) and Activity Avoidance (AA). The total
score, SF and AA revealed moderate to high correlations with other fear-avoidance
variables. CONCLUSIONS: The TSK-GV is a reliable and valid measure for assessing
the fear of movement/(re)injury.
PMID- 25138113
TI - Ten years of experience with first-trimester screening for fetal aneuploidy
employing biochemistry from gestational weeks 6+0 to 13+6.
AB - OBJECTIVES: To validate the performance of first-trimester screening for fetal
aneuploidy employing blood samples drawn in gestational weeks 6-13. METHODS:
Prospective combined first-trimester screening for fetal aneuploidy in Denmark
was validated in two large datasets: (1) a dataset from the Central Denmark
Region including 147,768 pregnancies from October 2003 to October 2013, and (2) a
national dataset including 220,739 pregnancies from January 2008 to August 2011.
RESULTS: For trisomy 21, the weekly median multiple of the median (MoM) increased
from 0.37 in week 6 to 0.70 in week 13 (pregnancy-associated plasma protein-A),
and from 0.99 in week 6 to 2.68 in week 13 (free betahCG). The overall detection
rate (DR) for fetal trisomy 21 was 91.2%. Employing blood samples from
gestational week 9, the DR was 97% (p = 0.05). For fetal trisomy 18, trisomy 13
and triploidy, the overall DRs after first-trimester screening were 79.5, 86 and
85%. In the national dataset, the overall DR for trisomy 21 was 86.3% ranging
from 89 (weeks 9 and 10) to 80% (weeks 12 and 13). CONCLUSION: The results from
both datasets show that blood sampling in gestational weeks 9-10 is a robust and
high-performance strategy, which can be applied for routine first-trimester
screening in clinical practice. (c) 2014 S. Karger AG, Basel.
PMID- 25138115
TI - Prospective study of spinal orthoses in women.
AB - BACKGROUND: There are not many clinical trials investigating the efficiency and
compliance of using spinal orthoses in the management of osteoporosis.
OBJECTIVES: The purpose of this study was to investigate the effect of long-term
use and the compliance of spinal orthoses in postmenopausal women with vertebral
fractures. STUDY DESIGN: Clinical trial of spinal orthoses in postmenopausal
women. METHODS: Women were separated into groups wearing different types of
orthoses (Spinomed, Osteomed, Spinomed active, and Spine-X). Isometric maximum
strength of trunk muscles (F/Wabdominals-extensors) was calculated and back pain
was assessed in all women. In addition, women completed a compliance
questionnaire about the use of the orthoses. RESULTS: Spinomed decreased pain (p
= 0.001) and increased trunk muscle strength (F/Wabdominals, p = 0.005 and
F/Wextensors, p = 0.003, respectively). The compliance of wearing an orthosis for
6 months was 66%. CONCLUSION: The results suggest that orthoses could be an
effective intervention for back pain and muscle strengthening in osteoporotic
women. CLINICAL RELEVANCE: In women with established osteoporosis, wearing
Spinomed orthosis for at least 2 h/day for 6 months decreased back pain
significantly and increased personal isometric trunk muscle strength. All spinal
orthoses could be valuable instruments to help all requested rehabilitation
programs like spine muscles' strengthening and postural correct behavior, but
only when used properly.
PMID- 25138114
TI - Effects of physical exertion on trans-tibial prosthesis users' ability to
accommodate alignment perturbations.
AB - BACKGROUND: It has long been reported that a range of prosthesis alignments is
acceptable in trans-tibial prosthetics. This range was shown to be smaller when
walking on uneven surfaces. It has also been argued that findings on gait with
prostheses that were obtained under laboratory conditions are limited in their
applicability to real-life environments. OBJECTIVES: This study investigated the
hypothesis that efforts to compensate for suboptimal alignments by active users
of trans-tibial prostheses become less effective when levels of physical exertion
increase. STUDY DESIGN: A 2 * 2 repeated-measures analysis of variance was
conducted to compare the effects of physical exertion and subtle alignment
perturbations on gait with trans-tibial prostheses. METHODS: The gait of eight
subjects with trans-tibial amputation was analyzed when walking with two
different prosthesis alignments and two different physical exertion levels. The
main and interaction effects were statistically evaluated. RESULTS: Bilateral
step length symmetry and measures of step variability within the same leg were
found to be affected by the intervention. There was no significant effect on
index variables that combined kinematic or kinetic measures. CONCLUSION: Findings
showed that persons with trans-tibial prostheses responded heterogeneously to the
interventions. For most variables, the research hypothesis could not be
confirmed. CLINICAL RELEVANCE: Findings support the practice of allotting several
sessions to the alignment of trans-tibial prostheses, as users' gait responds
differently to perturbations when external factors (e.g. exertion) change.
Furthermore, the found inhomogeneity in the population of persons with trans
tibial amputation supports the use of technical gait assessment methods in
clinical practice.
PMID- 25138116
TI - Political parties must tackle racial discrimination against staff and patients.
PMID- 25138117
TI - A prospective cross-sectional study on quality of life and treatment satisfaction
in type 2 diabetic patients with retinopathy without other major late diabetic
complications.
AB - BACKGROUND: To assess quality of life and treatment satisfaction in patients with
type 2 diabetes mellitus with diabetic retinopathy (DR) using validated
instruments, with comparison to patients without DR. METHODS: A prospective cross
sectional study was designed to assess the influence of retinopathy on quality of
life and treatment satisfaction in patients with type 2 diabetes mellitus who do
not have any other advanced late complications that could interfere with these
outcomes. We included 148 patients with DR and 149 without DR, all without other
advanced diabetic complications. Quality of life was assessed using the Audit of
Diabetes Dependent Quality of Life (ADDQoL) questionnaire, and treatment
satisfaction was assessed using the Diabetes Treatment Satisfaction Questionnaire
(DTSQ). Clinical and treatment variables related to diabetes were also collected.
The degree of DR was classified according to the International Clinical
Classification System. Multivariate linear regression models were used to model
the ADDQoL and DTSQ scores according to sociodemographical and clinical
characteristics, and to model the adjusted relationship of DTSQ with ADDQoL. In
DR patients, a subanalysis assessed the relationship of these scores with the
degree of retinopathy, severity of macular edema, and previous photocoagulation
treatment. RESULTS: DR was associated with significantly lower quality of life (p
< 0.001), when examining the two general quality of life items and most of the
specific domains. Concerning DTSQ, no difference was found in the total score,
and only two domains that assess the perception of glycemic control (hyper- and
hypoglycemia) showed a worse score in DR (p < 0.001 and p = 0.008, respectively).
Quality of life was significantly affected by the severity of DR, and treatment
satisfaction was significantly affected by the severity of macular edema. In the
multivariate analysis, a significant effect of the interaction between diabetes
duration, insulin therapy, and the presence of DR was found for both, ADDQoL and
DTSQ. CONCLUSION: In the absence of other major complications, DR has a negative
impact on quality of life in patients with type 2 diabetes. Further, treatment
satisfaction was not affected by the presence of DR.
PMID- 25138119
TI - Isolation of a dihydrobenzofuran lignan, icariside E4, with an antinociceptive
effect from Tabebuia roseo-alba (Ridley) Sandwith (Bignoniaceae) bark.
AB - The antinociceptive activity of icariside E4, a dihydrobenzofuran-type lignan
isolated from Tabebuia roseo-alba (Ridley) Sandwith (Bignoniaceae) bark, was
evaluated in mice by using chemical and thermal models of nociception.
Intraperitoneal (i.p.) administration of crude T. roseo-alba bark extract and its
methanol fraction inhibited acetic acid-induced abdominal constriction in mice.
Furthermore, i.p. administration of 0.1, 1, and 10 mg/kg of icariside E4 reduced
the number of writhes evoked by acetic acid injection by 46.9, 82.3, and 66.6%,
respectively. Icariside E4 administration had no effect in the first phase of the
formalin test, but it reduced nociceptive behavior in the second phase as
indicated by a reduction in the licking time. Icariside E4 did not modify thermal
nociception in the hot-plate test model, suggesting that it had a peripheral
antinociceptive action. The antinociceptive effect of icariside E4 in the
writhing test was reversed by pre-administration of glibenclamide, but not of
naloxone, atropine, yohimbine, or haloperidol. Together, these results indicated
that the antinociceptive activity of icariside E4 from T. roseo-alba in models of
chemical pain occurred through ATP-sensitive K(+) channel-dependent mechanisms.
PMID- 25138120
TI - Using gene genealogies to detect rare variants associated with complex traits.
AB - BACKGROUND AND OBJECTIVE: Standard population genetic theory says that
deleterious genetic variants are likely rare and fairly recently introduced.
However, can this expectation lead to more powerful tests of association between
diseases and rare genetic variation? The gene genealogy describes the
relationships between haplotypes sampled from the general population. Although
ancestral tree-based methods, inspired by the gene genealogy concept, have been
developed for finding associations with common genetic variants, here we ask
whether gene genealogies can help in identifying genomic regions containing
multiple rare causal variants. METHODS: With data simulated under several
demographic models and using known gene genealogies, we developed and compared
several tree-based statistics to determine which, if any, could detect the type
of clustering expected with rare causal variants and whether the genealogic tree
provides additional information about disease associations. RESULTS AND
CONCLUSIONS: We found that a novel statistic based on the scaled distance between
the tips of a tree performed better than other tree-based statistics. When data
were simulated with mild population growth, this statistic outperformed two
standard non-tree-based methods, showing that an ancestral tree-based approach
has potential for rare variant discovery.
PMID- 25138121
TI - Oral viscous budesonide as a first-line approach to esophageal stenosis in
epidermolysis bullosa: an open-label trial in six children.
AB - BACKGROUND: Esophageal and pharyngeal problems are common in the majority of
patients with epidermolysis bullosa (EB). Repeated blister formation and
ulceration, coupled with chronic inflammation, result in scarring and development
of esophageal strictures. OBJECTIVE: This study aimed to evaluate whether oral
viscous budesonide (OVB) was useful for treating esophageal structures in six
pediatric patients (aged 8-17 years) with EB who were affected by dysphagia and
esophageal strictures. METHODS: Patients were treated for 4 months with twice
daily oral budesonide nebulizer solution 0.5 mg/2 mL mixed with maltodextrin 5 g
and artificial sweeteners. RESULTS: One patient developed a severe oral mycotic
infection and discontinued treatment. The other five patients completed the
treatment regimen and displayed significantly lower stricture indices (SIs) post
treatment (mean SI +/- standard deviation 0.736 +/- 0.101 pre-treatment versus
0.558 +/- 0.162 post-treatment; p = 0.008). Patients experienced a mean SI
decrease of 0.178 (range 0.026-0.296), as well as improved dietary habits in the
absence of side effects. CONCLUSION: These findings indicated that topical
corticosteroids may significantly alleviate strictures in pediatric patients with
EB, thereby limiting the need for endoscopic dilation and considerably improving
patients' quality of life.
PMID- 25138122
TI - Perioperative and postoperative complications after Ophira mini sling operations.
AB - AIM: To evaluate perioperative and postoperative complications of mini sling
operations in the surgical treatment of female urinary incontinence. METHODS: The
study was comprised of 151 female patients with stress urinary incontinence (SUI)
or mixed incontinence (MUI) with predominant SUI patients who underwent the mini
sling procedure. The duration of the follow-up ranged from 6 to 21 months. All
women had positive cough stress tests preoperatively. The procedure was performed
under local (86.1 %) or spinal anesthesia (13.9 %) with the same mini slings for
all cases. Patients were examined in the outpatient clinic at 1 and 6 months
after surgery. RESULTS: The mean age was 49 years old (SD 10) with a range of 26
82. Of the 151 patients, 42 (27.8 %) presented MUI, while 109 (72.2 %) presented
SUI. Mean parity was 3 +/- 1. Mean body mass index was 28.9 +/- 3.5. 60 (39.7 %)
of the cases were postmenopausal. There were 73 women who participated in 6
months follow-ups and 78 women who did 1-year follow-ups. The mean operating time
was 13 +/- 3.1 min. There were no major intraoperative complications due to mini
sling surgery. 120 (79.5 %) patients were discharged the day following the
surgery. Ten patients (6.1 %) had de novo urge incontinence in their post
operative follow-ups which was resolved using anti-cholinergic drugs. Two
patients (1.2 %) required sling sections due to prolonged bladder outlet
obstruction. There were 15 patients that complained about de novo dyspareunia
(9.9 %). Vaginal mesh extrusion was reported in 18 (11.9 %) patients. The mean
preoperative and postoperative hemoglobin concentrations were 12.9 +/- 1.3 and
12.5 +/- 1.3 g/dL, respectively. CONCLUSION: The mini sling system can be
considered an easy and effective method for treating stress urinary incontinence
without major complication rates.
PMID- 25138123
TI - The effect of physical exercise on postpartum fitness, hormone and lipid levels:
a randomized controlled trial in primiparous, lactating women.
AB - PURPOSE: To evaluate the effect of an exercise training program combining low
impact dance aerobic, resistance and stretching exercise on physical fitness,
hormone and lipid levels of postpartum, primiparous, lactating women. METHODS:
Thirty seven primiparous, lactating women were randomly assigned at 4-6 weeks
postpartum to either follow an exercise training program of 50-60 min aerobic,
strengthening and stretching exercise, 3 days a week, for 12 weeks
(interventional group; n = 20) or no training program at all (control group; n =
17). The following parameters were measured at baseline and 12 weeks later: (1)
for evaluation of physical fitness: VO2max, muscular endurance, joint mobility
and body fat; (2) for evaluation of the lipidemic profile: triglyceride, total
cholesterol, HDL and LDL levels, and (3) levels of hormones associated with
lactation: prolactin, estradiol, cortisol, TSH, fT3 and fT4. RESULTS: After
completion of the exercise training program, comparisons between the
interventional and the control group showed statistically significant mean
changes in VO2max (p = 0.003), muscular endurance of the upper extremities (p <
0.001), and the abdomen (p < 0.001), flexibility (p = 0.042), and body fat (p =
0.007). There were no significant differences between the two groups in mean
changes of lipid and hormone levels. CONCLUSION: Implementation of a low-impact
exercise training program appears to improve physical fitness of postpartum
women, while it does not seem to affect lipid levels and lactation-associated
hormone levels. Hence, implementation of an exercise training program combining
low-impact dance aerobic, resistance and stretching exercise is feasible in
postpartum, primiparous, lactating women.
PMID- 25138124
TI - Cervical cancer screening in Germany: group-specific participation rates in the
state of Niedersachsen (Lower Saxony). A study with health insurance data.
AB - PURPOSE: The participation rates in cervical screenings are varying over
different countries. This is only partly due to the availability of organized
screening programs, as the rates are also varying between countries were such
programs were implemented. For Germany the level of knowledge is low, and
information are outdated. In order to improve the level of knowledge, we examined
whether the participation rates in cervical screenings in a large German
insurance population were changing over time, and whether these changes were
different with respect to age and qualification of the participating women.
METHODS: The analyses were based on the complete anonymised dataset of a large
statutory health insurance in Lower Saxony, Germany, with case numbers between
940,827 (2006) and 1,044,797 (2011) women aged 20 years and older. RESULTS:
Between 2006 and 2011 the overall annual participation rates were increasing from
44.8 to 47.6%. The highest rates occurred in women with the highest qualification
level, thus leading to increasing social differences over time. There was a peak
in the age group of 25-29 years from annually 60.3 (2006) to 60.2% (2011), and bi
annually from 77 to 77.1% with constantly decreasing rates up to the age of 60.
No substantial differences occurred between a 2- and a 3-year observation period.
CONCLUSIONS: Over time only small increases of participation rates in cervical
screenings occurred. These findings may be interpreted in favor of population
based screenings within an invitation program.
PMID- 25138125
TI - Associations between adipocyte fatty acid-binding protein and clinical parameters
in polycystic ovary syndrome.
AB - PURPOSE: We evaluated a possible association between serum adipocyte fatty acid
binding protein (A-FABP) levels and clinical parameters in women with polycystic
ovary syndrome (PCOS). METHODS: Our study included 86 women: 49 with PCOS (study
group), 37 with non-PCOS (control group). We recorded and analyzed age, body mass
index [BMI = weight (kg)/height (m)(2)], waist circumference, and blood pressure
and follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH, free
testosterone (fT), dehydroepiandrosterone sulfate, 17-OH progesterone, insulin,
glucose, triglyceride, high-density lipoprotein, low-density lipoprotein, very
low density lipoprotein, HOMA-IR, and A-FABP levels. RESULTS: The mean BMI, waist
circumference, and levels of serum LH, fT, LH/FSH, fasting insulin, and HOMA-IR
were significantly higher in PCOS patients (p < 0.05). Pearson correlation
analysis showed positive correlations of A-FABP levels with BMI and HOMA-IR
levels and a negative correlation between A-FABP and fT levels. A ROC curve
analysis found that BMI, waist circumference, and levels of fT, A-FABP, and HOMA
IR were discriminative parameters. CONCLUSION: Serum A-FABP levels may be a good
prognostic marker in predicting metabolic syndrome and cardiovascular diseases in
PCOS patients.
PMID- 25138126
TI - The influence of body weight on sexual function and quality of life in women with
polycystic ovary syndrome.
AB - PURPOSE: To assess sexual function (SF) and quality of life (QOL) in women with
polycystic ovary syndrome (PCOS). METHODS: A cross-sectional study was conducted
to assess 56 women with PCOS and 102 control women with regular menstrual cycles.
To assess SF and QOL in Brazilian women with PCOS with Female Sexual Function
Index (FSFI) and the WHOQOL-bref questionnaires. RESULTS: Women with PCOS had a
worse evaluation to arousal, lubrication, satisfaction, pain and total FSFI, and
there was no difference in sexual desire and orgasm. Besides, they had a worse
evaluation concerning health status than controls. The body mass index was
inversely correlated to the QOL, especially to the physical, psychological,
environment aspects and self-assessment of QOL, but it did not show correlation
to the SF. CONCLUSION: Women with PCOS had a worse sexual function and self
assessment of health condition in comparison to controls. The body weight as
isolated symptom was correlated to the worsening in quality of life, but not with
the worsening of sexual function.
PMID- 25138127
TI - Effects of electro-acupuncture on labor pain management.
AB - PURPOSE: To evaluate the effects of a non-pharmacologic electro-acupuncture
method at different acupoints on labor pain management. METHODS: Nulliparous
women under the maternity care of the Department of Obstetrics and Gynecology of
Sir Run Run Shaw Hospital were recruited and allocated into two experimental
groups (EX-B2 group and SP6 group) and one control group, each with 60 eligible
participants. Visual analog scale (VAS) was used to assess the pain during active
phase of labor before and 30, 60, 120 min after intervention. The duration of
active phase, the duration of second stage of labor, the duration of third stage
of labor, use of oxytocin, neonatal birth weight, neonatal Apgar score at 1 and 5
min were considered as secondary outcomes of this study. RESULTS: After 30 min
intervention, the mean VAS scores of both EX-B2 group and SP6 group were
significantly decreased compared with the control group (P < 0.01); however, no
significant difference was observed between the two experimental groups (P >
0.05). After 60 and 120 min intervention, the mean VAS scores of EX-B2 group were
significantly lower than SP-6 group (P < 0.05). Both EX-B2 group and SP6 group
had significant lower VAS scores after interventions and shorter time used in
active phase of labor than the control group (P < 0.05). CONCLUSIONS: The study
revealed that the application of electro-acupuncture at EX-B2 and SP6 acupoints
could be used as a non-pharmacologic method to reduce labor pain and shorten the
duration of active phase of labor.
PMID- 25138128
TI - Oral versus vaginal misoprostol for induction of labor in Enugu, Nigeria: a
randomized controlled trial.
AB - OBJECTIVE: The study aimed at comparing the effectiveness and maternal
satisfaction of oral misoprostol with vaginal misoprostol for induction of labor
at term. MATERIALS AND METHODS: A randomized controlled trial of 140 term
pregnant women at the University of Nigeria Teaching Hospital Enugu, Nigeria, was
conducted from April 2011 to May 2012. The women were equally randomized into two
groups (A and B) to receive oral and vaginal misoprostol, respectively. RESULTS:
The vaginal route reduced the mean induction-vaginal delivery interval by four
and-half hours (20.7 +/- 12.1 vs. 16.2 +/- 10.4; mean difference: 4.50, 95% CI
0.63-0.82; p = 0.02). Furthermore, the mean dose of misoprostol required to
achieve induction of labor and the mean duration of oxytocin augmentation when
indicated were significantly less in the vaginal group than in the oral group
(2.5 +/- 1.3 vs. 2.0 +/- 1.1; mean difference: 0.50, 95% CI 0.10-0.90; p = 0.02
and 4.6 +/- 3.2 vs. 3.4 +/- 3.1; mean difference: 1.20, 95% CI 0.15-0.23; p =
0.03 respectively). However, neonatal complications and maternal satisfaction
were similar between the two groups. CONCLUSION: Both routes of administration
are effective in the induction of labor at term and have comparable maternal
satisfaction. However, the vaginal route has the added advantage of shorter
induction-delivery interval among others, and thus should be highly considered
when induction of labor is indicated at term.
PMID- 25138130
TI - Advances in chalcones with anticancer activities.
AB - Chalcones are naturally occurring compounds exhibiting broad spectrum biological
activities including anticancer activity through multiple mechanisms. Literature
on anticancer chalcones highlights the employment of three pronged strategies,
namely; structural manipulation of both aryl rings, replacement of aryl rings
with heteroaryl scaffolds, molecular hybridization through conjugation with other
pharmacologically interesting scaffolds for enhancement of anticancer properties.
Methoxy substitutions on both the aryl rings (A and B) of the chalcones,
depending upon their positions in the aryl rings appear to influence anticancer
and other activities. Similarly, heterocyclic rings either as ring A or B in
chalcones, also influence the anticancer activity shown by this class of
compounds. Hybrid chalcones formulated by chemically linking chalcones to other
prominent anticancer scaffolds such as pyrrol[2,1-c][1,4]benzodiazepines,
benzothiazoles, imidazolones have demonstrated synergistic or additive
pharmacological activities. The successful application of these three pronged
strategies for discovering novel anticancer agents based on chalcone scaffold has
resulted in many novel and chemically diverse chalcones with potential
therapeutic application for many types of cancer. This review summarizes the
concerted efforts expended on the design and development of anticancer chalcones
recorded in recent literature and also provides an overview of the patents
published in this area between 2007 and 2014 (WO2013022951, WO201201745 &
US2012029489).
PMID- 25138129
TI - Identification of myeloid-derived suppressor cells in the synovial fluid of
patients with rheumatoid arthritis: a pilot study.
AB - BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous
population of innate immune cells with a granulocyte-like or monocyte-like
phenotype and a unique ability to suppress T-cell responses. MDSCs have been
shown to accumulate in cancer patients, but recent studies suggest that these
cells are also present in humans and animals suffering from autoimmune diseases.
We previously identified MDSCs in the synovial fluid (SF) of mice with
experimental autoimmune arthritis. The goal of the present study was to identify
MDSCs in the SF of patients with rheumatoid arthritis (RA). METHODS: RA SF cells
were studied by flow cytometry using antibodies to MDSC cell surface markers as
well as by analysis of cell morphology. The suppressor activity of RA SF cells
toward autologous peripheral blood T cells was determined ex vivo. We employed
both antigen-nonspecific (anti-CD3/CD28 antibodies) and antigen-specific
(allogeneic cells) induction systems to test the effects of RA SF cells on the
proliferation of autologous T cells. RESULTS: SF from RA patients contained MDSC
like cells, the majority of which showed granulocyte (neutrophil)-like phenotype
and morphology. RA SF cells significantly suppressed the proliferation of anti
CD3/CD28-stimulated autologous T cells upon co-culture. When compared side by
side, RA SF cells had a more profound inhibitory effect on the alloantigen
induced than the anti-CD3/CD28-induced proliferation of autologous T cells.
CONCLUSION: MDSCs are present among RA SF cells that are commonly regarded as
inflammatory neutrophils. Our results suggest that the presence of neutrophil
like MDSCs in the SF is likely beneficial, as these cells have the ability to
limit the expansion of joint-infiltrating T cells in RA.
PMID- 25138131
TI - Patent analysis as a tool for research planning: study on natural based
therapeutics against cancer stem cells.
AB - Medicines developed from traditional systems are well known for their various
important pharmaceutical uses. Cancer has been known since ancient times and has
been mentioned in the ancient Ayurvedic books. Thus natural based products play a
significant role in cancer chemotherapeutics. Further, approximately 70% of
anticancer compounds are based on natural products or have been derived from
their structural scaffolds. Hence, there is a growing interest for developing
medicines from these natural resources. Amongst the methods of treating cancer,
therapies targeting cancer stem cell are found to control metastatic tumor which
is a newly identified factor associated with relapse. This patent review aims to
highlight the use of natural products to treat cancer by targeting the cancer
stem cells. The review will also provide insights into the reported mechanisms by
which the natural products act in order to suppress or kill cancer stem cells.
The analysis has been done using various criteria such as the patenting trend
over the years, comparison of active assignee and a comparison of the technical
aspects as disclosed in the different patent documents. The analysis further
highlights different bioactives, the scaffolds of which could thus be a promising
candidate in the development of anti-cancer drugs by targeting the cancer stem
cells. The technical aspects covered in this review include: Bioactives and
formulations comprising the extracts or bioactives, their mode of action and the
type of assay considered to study the efficacy of the natural products. Further
the mapping has helped us to identify potential therapeutic areas to evaluate
herbs/bioactives and their uses for developing new formulations.
PMID- 25138132
TI - Fetal myelomeningocele repair: the post-MOMS experience at the Children's
Hospital of Philadelphia.
AB - BACKGROUND: Fetal myelomeningocele (fMMC) repair has become accepted as a
standard of care option in selected circumstances. We reviewed our outcomes for
fMMC repair from referral and evaluation through surgery, delivery and neonatal
discharge. MATERIAL AND METHODS: All patients referred for potential fMMC repair
were reviewed from January 1, 2011 through March 7, 2014. Maternal and neonatal
data were collected on the 100 patients who underwent surgery. RESULTS: 29% of
those evaluated met the criteria and underwent fMMC repair (100 cases). The
average gestational age was 21.9 weeks at evaluation and 23.4 weeks at fMMC
repair. Complications included membrane separation (22.9%), preterm premature
rupture of membranes (32.3%) and preterm labor (37.5%). Average gestational age
at delivery was 34.3 weeks and 54.2% delivered at >=35 weeks. The perinatal loss
rate was 6.1% (2 intrauterine fetal demises and 4 neonatal demises); 90.8% of
women delivered at the Children's Hospital of Philadelphia and 3.4% received
transfusions. With regard to the neonates, 2 received ventriculoperitoneal shunts
prior to discharge; 71.1% of neonates had no evidence of hindbrain herniation on
MRI. Of the 80 neonates evaluated, 55% were assigned a functional level of one or
more better than the prenatal anatomic level. CONCLUSION: In an experienced
program, maternal and neonatal outcomes for patients undergoing fMMC repair are
comparable to results of the MOMS trial.
PMID- 25138134
TI - Cytomegalovirus central nervous system compartmentalization in a patient
presenting with AIDS.
AB - Cytomegalovirus (CMV) central nervous system involvement is uncommon and hardly
diagnosed because it can mimic many different conditions. We here present a case
of an HIV-positive patient with neurological signs and symptoms (headache,
asthenia, confusion, hallucinations, ataxia) with concurrent opportunistic
diseases (neurotoxoplasmosis, disseminated Kaposi's sarcoma, disseminated CMV
infection). CMV CNS involvement was not initially considered given the observed
multiple comorbidities: antiviral treatment duration was probably not adequate
given the end-organ disease. Concomitantly, plasma CMV DNA was undetectable while
cerebrospinal fluid viral load was 31,340 copies/ml. Ganciclovir treatment
followed by oral valganciclovir maintenance was associated with the slow
disappearance of symptoms, the improvement of MRI images and the persistent
undetectability of CMV DNA. The case here reported highlights the challenges of
diagnosing CMV encephalitis in HIV-positive patients (with several cerebral
comorbidities), the incomplete knowledge of the appropriate treatment for such a
disease and the possibility of CMV replication in the cerebrospinal fluid despite
undetectable plasma CMV DNA.
PMID- 25138135
TI - A vanishing lymphoma in the cheek.
AB - BACKGROUND: We describe the unusual case of a 66-year-old woman who presented
with a cheek mass that completely abated with oral steroids. CASE REPORT:
Multiple separate biopsies of the mass were negative or inconclusive. MRI
revealed a large mass, yet after a short steroid course, this mass was completely
undetectable on clinical examination. A repeat biopsy eventually revealed
follicular lymphoma. DISCUSSION: Lymphomas are known to be steroid sensitive; the
medication is an essential component of the common CHOP therapy. While known to
occur in the central nervous system, to the best of our knowledge, the presence
of a 'vanishing' lymphoma has not been documented in the head and neck. We
discuss the likely physiology of the vanishing lymphoma, and the diagnostic
difficulty it presents. CONCLUSION: When a lymphoma is suspected, patient care
may be optimized if biopsy is delayed until steroids have been discontinued.
PMID- 25138136
TI - The association between family meals and early-adolescents' weight status change
in the context of parental discipline practices: the moderating roles of
ethnicity and acculturation.
AB - This study examines the interactions among family meals, parental discipline
practices, ethnicity, and acculturation on weight status change in a diverse
sample of early-adolescents. Data were obtained from the Early Childhood
Longitudinal Study-Kindergarten Cohort (ECLS-K), a nationally representative
sample of children who entered kindergarten during 1998-1999. In fifth grade,
parents reported on child and household routines. In fifth and eighth grade,
children were weighed and measured at school. Above and beyond covariates, less
acculturated Hispanic adolescents who ate more family meals and experienced low
parental behavioral control in fifth grade were less likely to make a healthy
change (gamma = -0.15, OR = 0.86, p < 0.05) and more likely to make an unhealthy
change (gamma = 0.32, OR = 1.38, p < 0.05) in their weight status by eighth
grade, when compared to White Non-Hispanic adolescents. The implications of
interactions among family meals, parental discipline practices, and healthy
weight promotion are discussed in the context of ethnicity and acculturation.
PMID- 25138137
TI - Disparities in Access to Prenatal Care Services for African Immigrant Women in
Spain.
AB - This retrospective cohort study compares the utilization of prenatal care between
African immigrant and native Spanish women. For 2007-2010, we identified 231
pregnant African immigrant women. The native-born population sample was obtained
by simple random sampling in a 1:3 ratio. The Kessner Index (KI) and our Own
Index (OI) were applied to rate prenatal care adequacy in three categories
(adequate, intermediate, and inadequate). Odds ratios (ORs) were estimated using
non-conditional logistic regression. Prenatal care was adequate according to the
indexes (KI or OI) in 21.3 and 25.8% of North Africans and in 22.5 and 30.4% of
sub-Saharan Africans. The ORs of inadequacy when adjusted for maternal age,
social risk factors, and previous reproductive outcomes were 30.32 and 35.47 (KI
or OI) in North and 64.43 and 67.93 in sub- Saharan Africans. These results
suggest significant differences in obtaining adequate prenatal care between
immigrant and native Spanish women.
PMID- 25138138
TI - Evaluating Job Demands and Control Measures for Use in Farm Worker Health
Surveillance.
AB - Workplace stress likely plays a role in health disparities; however, applying
standard measures to studies of immigrants requires thoughtful consideration. The
goal of this study was to determine the appropriateness of two measures of
occupational stressors ('decision latitude' and 'job demands') for use with
mostly immigrant Latino farm workers. Cross-sectional data from a pilot module
containing a four-item measure of decision latitude and a two-item measure of job
demands were obtained from a subsample (N = 409) of farm workers participating in
the National Agricultural Workers Survey. Responses to items for both constructs
were clustered toward the low end of the structured response-set. Percentages of
responses of 'very often' and 'always' for each of the items were examined by
educational attainment, birth country, dominant language spoken, task, and crop.
Cronbach's alpha, when stratified by subgroups of workers, for the decision
latitude items were (0.65-0.90), but were less robust for the job demands items
(0.25-0.72). The four-item decision latitude scale can be applied to occupational
stress research with immigrant farm workers, and potentially other immigrant
Latino worker groups. The short job demands scale requires further investigation
and evaluation before suggesting widespread use.
PMID- 25138139
TI - Sensitivity and false alarm rate of a fall sensor in long-term fall detection in
the elderly.
AB - BACKGROUND: About a third of home-dwelling older people fall each year, and
institutionalized older people even report a two- or threefold higher rate for
falling. Automatic fall detection systems have been developed to support the
independent and secure living of the elderly. Even though good fall detection
sensitivity and specificity in laboratory settings have been reported, knowledge
about the sensitivity and specificity of these systems in real-life conditions is
still lacking. OBJECTIVE: The aim of this study was to evaluate the long-term
fall detection sensitivity and false alarm rate of a fall detection prototype in
real-life use. METHODS: A total of 15,500 h of real-life data from 16 older
people, including both fallers and nonfallers, were monitored using an
accelerometry-based sensor system with an implemented fall detection algorithm.
RESULTS: The fall detection system detected 12 out of 15 real-life falls, having
a sensitivity of 80.0%, with a false alarm rate of 0.049 alarms per usage hour
with the implemented real-time system. With minor modification of data analysis
the false alarm rate was reduced to 0.025 false alarms per hour, equating to 1
false fall alarm per 40 usage hours. CONCLUSION: These data suggest that
automatic accelerometric fall detection systems might offer a tool for improving
safety among older people.
PMID- 25138140
TI - Temporary arterial embolization of liver parenchyma with degradable starch
microspheres (EmboCept(r)S) in a swine model.
AB - BACKGROUND: This study aimed to evaluate the embolic properties, time to
reperfusion, and histologic changes in temporary embolization of liver tissue
with degradable starch microspheres (DSM) in a swine model. METHODS: In four
adult minipigs, DSMs were injected into the right or left hepatic artery on the
lobar level until complete stasis of the blood flow was detectable
angiographically. The time required to complete angiographically determined
reperfusion was noted. The animals were killed 3 h after complete reperfusion,
and samples were taken from the liver. Histologic examinations of the embolized
liver parenchyma and untreated tissue were performed. RESULTS: Hepatic arterial
embolization using DSMs was technically successful in all cases, with complete
blood flow stasis shown by control angiography. A single vial of DSMs (450 mg/7.5
ml) was sufficient to embolize a whole liver lobe in all cases. Angiography
showed complete reconstitution of hepatic arterial perfusion after a mean time to
reperfusion of 32 +/- 6.1 min (range, 26-39 min). Hematoxylin and eosin staining
showed no histologically detectable differences between untreated tissue and
parenchyma embolized with DSMs except for mild sinusoidal congestion in one case.
Indirect in situ DNA nick end labeling staining (TUNEL) showed only single
positive hepatocytes, indicating apoptosis. CONCLUSION: Temporary embolization of
the hepatic artery using DSMs is feasible with complete reperfusion after 30 min
in pigs. Even after complete arterial blood flow stasis, no extensive tissue
damage to the embolized liver parenchyma was observed at histologic examinations
in this short-term study.
PMID- 25138141
TI - Antibacterial activity of biogenic silver nanoparticles synthesized with gum
ghatti and gum olibanum: a comparative study.
AB - Presently, silver nanoparticles produced by biological methods have received
considerable significance owing to the natural abundance of renewable, cost
effective and biodegradable materials, thus implementing the green chemistry
principles. Compared with the nanoparticles synthesized using chemical methods,
most biogenic silver nanoparticles are protein capped, which imparts stability
and biocompatibility, and enhanced antibacterial activity. In this study, we
compared the antibacterial effect of two biogenic silver nanoparticles produced
with natural plant gums: gum ghatti and gum olibanum against Gram-negative and
Gram-positive bacteria. Bacterial interaction with nanoparticles was probed both
in planktonic and biofilm modes of growth; employing solid agar and liquid broth
assays for inhibition zone, antibiofilm activity, inhibition of growth kinetics,
leakage of intracellular contents, membrane permeabilization and reactive oxygen
species production. In addition, cytotoxicity of the biogenic nanoparticles was
evaluated in HeLa cells, a human carcinoma cell line. Antibacterial activity and
cytotoxicity of the silver nanoparticles synthesized with gum ghatti (Ag NP-GT)
was greater than that produced with gum olibanum (Ag NP-OB). This could be
attributed to the smaller size (5.7 nm), monodispersity and zeta potential of the
Ag NP-GT. The study suggests that Ag NP-GT can be employed as a cytotoxic
bactericidal agent, whereas Ag NP-OB (7.5 nm) as a biocompatible bactericidal
agent.
PMID- 25138143
TI - Contact lenses: new devices for nucleotide delivery in ocular pathologies.
PMID- 25138142
TI - Vancomycin blocks autophagy and induces interleukin-1beta release in macrophages.
AB - Systemic inflammatory response syndrome (SIRS) is a serious condition that can
cause organ failure as an exaggerated immunoresponse to the infection or other
causes. Recently, autophagy was reported as a key process that regulates
inflammatory responses in macrophages. Vancomycin is one of the most commonly
prescribed antibiotics for sepsis treatment or following surgery. However, there
are no studies on how vancomycin affects autophagy or inflammation. Here, we
treated macrophage cell lines with vancomycin and lipopolysaccharides and found
that vancomycin blocks autophagy and increases inflammatory responses. This
finding suggests that vancomycin should be more cautiously administered in order
to prevent unwanted SIRS during sepsis.
PMID- 25138144
TI - Treatment moderators of cognitive behavior therapy to reduce aggressive behavior:
a meta-analysis.
AB - Maladaptive aggression in adolescents is an increasing public health concern.
Cognitive Behavior Therapy (CBT) is one of the most common and promising
treatments of aggression. However, there is a lack of information on predictors
of treatment response regarding CBT. Therefore, a meta-analysis was performed
examining the role of predictors on treatment response of CBT. Twenty-five
studies were evaluated (including 2,302 participants; 1,580 boys and 722 girls),
and retrieved through searches on PubMed, PsycINFO and EMBASE. Effect sizes were
calculated for studies that met inclusion criteria. Study population differences
and specific CBT characteristics were examined for their explanatory power. There
was substantial variation across studies in design and outcome variables. The
meta-analysis showed a medium treatment effect for CBT to reduce aggression
(Cohen'd = 0.50). No predictors of treatment response were found in the meta
analysis. Only two studies did examine whether proactive versus reactive
aggression could be a moderator of treatment outcome, and no effect was found of
this subtyping of aggression. These study results suggest that CBT is effective
in reducing maladaptive aggression. Furthermore, treatment setting and duration
did not seem to influence treatment effect, which shows the need for development
of more cost-effective and less-invasive interventions. More research is needed
on moderators of outcome of CBT, including proactive versus reactive aggression.
This requires better standardization of design, predictors, and outcome measures
across studies.
PMID- 25138146
TI - Bioinspired design and assembly of layered double hydroxide/poly(vinyl alcohol)
film with high mechanical performance.
AB - Inspired by the hierarchical structure and excellent mechanical performance of
nacre, LDH nanosheets with an appropriate aspect ratio to withstand significant
loads and at the same time allow for rupture under the pull-out mode were
synthesized as artificial building blocks for the fabrication of nacre-like
films. Multilayered PVA/LDH films with a high tensile strength and ductility were
prepared for the first time by bottom-up layer-by-layer assembly of pretreated
LDH nanosheets and spin-coating of PVA. The weight fraction of inorganic LDH
platelets in the hybrid PVA/LDH films (wp) was controlled by changing the
concentration of PVA solution applied in the spin-coating process. The resulting
films revealed that the PVA/LDH hybrid films were piled close together to form a
well-defined stratified structure resembling the brick-and-mortar structure of
natural nacre. In the hybrid films, the content of inorganic LDH platelets was
comparable to the value in nacre, up to 96.9 wt %. It could be clearly seen that
the mechanical performance of the as-prepared PVA/LDH films was greatly improved
by increasing the rigid building-block LDHs. The tensile strength of the 2 wt %
PVA/LDH hybrid film reached a value of 169.36 MPa, thus exceeding the strength of
natural nacre and reaching 4 times that of a pure PVA film. Meanwhile, its
elastic modulus was comparable to that of lamellar bone.
PMID- 25138147
TI - Relationships between the effect of sunitinib and immature blood vessels in
metastatic renal cell cancer.
AB - INTRODUCTION: This study was conducted to investigate the relationships between
the effect of sunitinib and immature microvessels which are not covered by
pericytes. MATERIALS AND METHODS: This study involved 29 patients with clear-cell
renal cell carcinoma (RCC) who took sunitinib after radical nephrectomy or biopsy
due to metastatic RCC. Associations among clinicopathological factors, responses
to sunitinib, and patient survival were reviewed. CD31 was used to stain
endothelial cells, and anti-alpha-smooth muscle actin was used to stain
pericytes. Immature vessels were defined as vessels that were positive only for
CD31 staining. A high pericyte coverage was defined as a rate of pericyte
coverage above 40%. RESULTS: Partial responses, disease stabilization, and
disease progression constituted 51.7, 10.4, and 37.9% of cases, respectively.
Nine cases had a low pericyte coverage (31.0%). In the high-pericyte-coverage
group, the number of metastatic sites was smaller (p=0.003). The overall response
rate to sunitinib was greater in the high-pericyte-coverage group than in the low
pericyte-coverage group (p=0.027). The median overall survival and the median
progression-free survival were not significantly different between the high- and
low-pericyte-coverage groups. CONCLUSION: In the high-pericyte-coverage group,
the overall response rates to sunitinib were higher, and the numbers of
metastatic sites were smaller.
PMID- 25138145
TI - Chronic multisite pain in adolescent girls and boys with emotional and behavioral
problems: the Young-HUNT study.
AB - The aim of this study was to assess the prevalence of chronic multisite pain with
high disability in relation to emotional or behavioral problems and resilience
factors in adolescence. A second aim was to investigate if resilience factors
could attenuate the associations between psychiatric symptoms and chronic
multisite pain. The study was based on a large cross-sectional study carried out
in Norway between 2006 and 2008 and included 7,070 adolescents aged 13-19 years.
Chronic multisite pain was defined as pain at least once a week during the last 3
months, scoring high on a disability index, and occurring in three or more
locations. Chronic multisite pain was prevalent among adolescents with high
scores (>85%) for anxiety/depression, social anxiety, conduct or attention
problems (22.8-31.0 for girls, 8.8-19.0% for boys). Several coexistent
psychiatric symptoms increased the prevalence of chronic multisite pain for both
girls and boys. Resilience factors, including high self-esteem, seldom feeling
lonely, and high scores for family cohesion or social competence, were associated
with a lower prevalence and markedly attenuated the association between
psychiatric symptoms and chronic multisite pain. Psychiatrists should be careful
to assess and treat comorbid chronic pain in adolescents with emotional or
behavioral problems.
PMID- 25138148
TI - Donor-transmitted HTLV-1-associated myelopathy in a kidney transplant recipient-
case report and literature review.
AB - Clinical disease due to human T cell lymphotropic virus type 1 (HTLV-1), a
retrovirus endemic in certain regions of the world, is rarely reported after
solid organ transplantation. In 2009, universal deceased donor organ screening
for HTLV-1 was discontinued in the United States. We report the first case of
donor-derived HTLV-1-associated myelopathy in a kidney transplant recipient from
the United States. The patient, who was HTLV-1-seronegative prior to
transplantation, likely acquired HTLV-1 infection from a seropositive organ
donor. In this era when screening of donors and recipients for HTLV infection is
not mandatory, clinicians should be vigilant in recognizing the risk and
potential occurrence of this donor-derived infection in recipients with
epidemiologic exposures.
PMID- 25138150
TI - Micropercutaneous Nephrolithotomy in the Management of Bilateral Renal Stones in
a 7-Month-Old Infant: The Youngest Case in the Literature.
AB - During infancy, the renal parenchyma and pelvicalyceal system are relatively
fragile. Therefore, percutaneous nephrolithotomy for the management of renal
stones in this age group is a challenging procedure for urologists. Herein, we
present the uneventful management of bilateral renal stones using
micropercutaneous nephrolithotomy (microperc) administered to a 7-month-old
infant with recurrent urinary tract infections. In this paper, the advantages and
disadvantages of the microperc procedure are discussed. As far as we know, our
patient is the youngest case in whom the microperc procedure has been performed.
PMID- 25138149
TI - Reversible cerebral vasoconstriction syndrome: a comprehensive update.
AB - Reversible cerebral vasoconstriction syndrome (RCVS) is a clinico-radiological
syndrome characterized by recurrent thunderclap headache, with or without
neurologic symptoms, and reversible vasoconstriction of cerebral arteries. RCVS
affects patients in various racial and ethnic groups and in all age groups,
although most commonly in the fourth decade of life. Many conditions and
exposures have been linked to RCVS, including vasoactive drugs and the peripartum
period. Disturbance of the cerebral vascular tone is thought to contribute to the
disease's pathophysiology. RCVS generally follows a monophasic course. Associated
strokes and cerebral hemorrhages are not uncommon. In this review we will attempt
to provide a comprehensive overview of RCVS, with emphasis on the controversies
in the field and the newest findings in the reported literature.
PMID- 25138151
TI - The effectiveness of collaborative care for people with memory problems in
primary care: results of the CAREDEM case management modelling and feasibility
study.
AB - BACKGROUND: People with dementia and their families need support in different
forms, but currently services are often fragmented with variable quality of care.
Case management offers a way of co-ordinating services along the care pathway and
therefore could provide individualised support; however, evidence of the
effectiveness of case management for dementia is inconclusive. OBJECTIVE: To
adapt the intervention used in a promising case management project in the USA and
test its feasibility and acceptability in English general practice. DESIGN: In
work package 1, a design group of varied professionals, with a carer and staff
from the voluntary sector, met six times over a year to identify the skills and
personal characteristics required for case management; protocols from the US
study were adapted for use in the UK. The feasibility of recruiting general
practices and patient-carer dyads and of delivering case management were tested
in a pilot study (work package 2). An embedded qualitative study explored
stakeholder views on study procedures and case management. SETTING: Four general
practices, two in the north-east of England (Newcastle) one in London and one in
Norfolk, took part in a feasibility pilot study of case management. PARTICIPANTS:
Community-dwelling people with dementia and their carers who were not already
being case managed by other services. INTERVENTION: A social worker shared by the
two practices in the north-east and practice nurses in the other two practices
were trained to deliver case management. We aimed to recruit 11 people with
dementia from each practice who were not already being case managed. MAIN OUTCOME
MEASURES: Numbers of people with dementia and their carers recruited, numbers and
content of contacts, needs identified and perceptions of case management among
stakeholders. RESULTS: Recruitment of practices and patients was slow and none of
the practices achieved its recruitment target. It took more than 6 months to
recruit a total of 28 people with dementia. Practice Quality and Outcome
Framework registers for dementia contained only 60% of the expected number of
people, most living in care homes. All stakeholders were positive about the
potential of case management; however, only one of the four practices achieved a
level of case management activity that might have influenced patient and carer
outcomes. Case managers' activity levels were not related solely to time
available for case management. Delivery of case management was hindered by
limited clarity about the role, poor integration with existing services and a
lack of embeddedness within primary care. There were discrepancies between case
manager and researcher judgements about need, and evidence of a high threshold
for acting on unmet need. The practice nurses experienced difficulties in ring
fencing case management time. CONCLUSIONS: The model of case management developed
and evaluated in this feasibility study is unlikely to be sustainable in general
practice under current conditions and in our view it would not be appropriate to
attempt a definitive trial of this model. This study could inform the development
of a case management role with a greater likelihood of impact. Different
approaches to recruiting and training case managers, and identifying people with
dementia who might benefit from case management, are needed, as is exploration of
the scale of need for this type of working. TRIAL REGISTRATION: Current
Controlled Trials ISRCTN74015152. FUNDING: This project was funded by the
National Institute for Health Research (NIHR) Health Technology Assessment
programme and will be published in full in Health Technology Assessment; Vol. 18,
No. 52. See the NIHR Journals Library website for further project information.
PMID- 25138152
TI - Vocal fold paresis accompanying vocal fold polyps.
AB - The aim of this study was to evaluate patients with vocal fold polyps using
laryngeal electromyography (LEMG) for the presence of vocal fold paresis and to
compare transnasal fiberoptic and rigid stroboscopic findings between polyp
patients with normal LEMG and with vocal fold paresis. Thirty-five patients with
a vocal fold polyp underwent transnasal fiberoptic laryngoscopy, rigid
laryngostroboscopy, and LEMG. The findings were compared between the LEMG
confirmed vocal fold paresis patients and the normal LEMG patients. LEMG resulted
in a diagnosis of unilateral or bilateral vocal fold paresis in 17 of 35 patients
(48.6 %). More men than women with vocal fold polyps had vocal fold paresis (p <
0.05). The vocal fold paresis group had higher presence of axial rotation and
hypomobility of vocal folds, higher asymmetry of vertical height of vocal folds,
and less presence of longitudinal stretch of vocal folds (p < 0.05). Medial
lateral compression of the false vocal folds and anterior-posterior approximation
of the larynx did not show any difference between the groups. No significant
difference was found in vibratory wave characteristics between the groups through
rigid laryngostroboscopy. Vocal fold paresis was present in almost half of the
patients with vocal fold polyps. Paresis can only be accurately diagnosed with
LEMG. Transnasal fiberoptic laryngoscopic examination is helpful to recognize
vocal fold paresis in vocal fold polyp patients, while stroboscopic examination
is not useful to identify it in vocal fold polyp patients.
PMID- 25138153
TI - In vivo over-expression of KGF mimic human middle ear cholesteatoma.
AB - We reported previously that keratinocyte growth factor (KGF), a mesenchymal cell
derived paracrine growth factor, plays an important role in middle ear
cholesteatoma formation, which is characterized by marked proliferation of
epithelial cells. Here, we investigated whether KGF, the main factor that induces
cholesteatoma, overexpression in vivo results in the formation of cholesteatoma.
Flag-hKGF cDNA driven by CMV14 promoter was transfected through electroporation
into the external auditory canal (EAC) of rats once (short-term model) or five
times on every fourth day (long-term model). Ears transfected with empty vector
were used as controls. Successful transfection of plasmids into epithelial and
stromal cells was confirmed by Flag immunohistochemistry. In the short-term
model, the intensity of KGF protein was the strongest in hKGF transfected ear at
day 4. KGF expression induced epithelial cell proliferation, reaching a peak
level at day 4 and then decreased later, while in the long-term model, KGF
expression in the EAC led to middle ear cholesteatoma formation. In conclusion,
we described here a new experimental model of human middle ear cholesteatoma, and
demonstrated that KGF and KGF receptor paracrine action play an essential role in
middle ear cholesteatoma formation in an in vivo model.
PMID- 25138154
TI - Renegotiating cultural practices as a result of HIV in the eastern region of
Malawi.
AB - A number of studies have shown that HIV awareness is very high among Malawians
and yet infection rates are rising. Local cultural practices have been identified
as contributing to this contradictory situation. Using data from 12 focus-group
discussions collected in Balaka, Zomba, Machinga and Mangochi, the paper explores
the reformulation of nine cultural practices as a preventive measure against HIV.
The study reveals that cultural practices that involve sexual acts for completion
are mediated through condoms and HIV tests. The study also shows that traditional
herbs known for healing ailments are repurposed to symbolise sexual acts. We
conclude that the idea of repurposing offers an avenue in which initiation and
cleansing rites that involve sexual acts are replaced by other semiotics such as
a traditional medicine called mtela. We also conclude that the modifications to
cultural practices do not indicate complete abandonment of associated traditions,
rather, they constitute the renegotiation of cultural practices and meanings
associated with particular rites of passage. Lastly, we propose that a
comprehensive prevention programme needs to be part of a wider national HIV
prevention effort combining a women and child rights and empowerment agenda and,
critically, lifestyle lessons in a process of cultural renegotiation.
PMID- 25138156
TI - First-hand sensory experience plays a limited role in children's early
understanding of seeing and hearing as sources of knowledge: evidence from
typically hearing and deaf children.
AB - One early-developing component of theory of mind is an understanding of the link
between sensory perception and knowledge formation. We know little about the
extent to which children's first-hand sensory experiences drive the development
of this understanding, as most tasks capturing this early understanding target
vision, with less attention paid to the other senses. In this study, 64 typically
hearing children (Mage = 4.0 years) and 21 orally educated deaf children (Mage
= 5.44 years) were asked to identify which of two informants knew the identity of
a toy animal when each had differing perceptual access to the animal. In the
'seeing' condition, one informant saw the animal and the other did not; in the
'hearing' condition, one informant heard the animal and the other did not. For
both hearing and deaf children, there was no difference between performance on
hearing and seeing trials, but deaf children were delayed in both conditions.
Further, within both the hearing and deaf groups, older children outperformed
younger children on these tasks, indicating that there is a developmental
progression. Taken together, the pattern of results suggests that experiences
other than first-hand sensory experiences drive children's developing
understanding that sensory perception is associated with knowledge.
PMID- 25138155
TI - Random variation in rectal position during radiotherapy for prostate cancer is
two to three times greater than that predicted from prostate motion.
AB - OBJECTIVE: Radiotherapy for prostate cancer does not explicitly take into account
daily variation in the position of the rectum. It is important to accurately
assess accumulated dose (DA) to the rectum in order to understand the
relationship between dose and toxicity. The primary objective of this work was to
quantify systematic (Sigma) and random (sigma) variation in the position of the
rectum during a course of prostate radiotherapy. METHODS: The rectum was manually
outlined on the kilo-voltage planning scan and 37 daily mega-voltage image
guidance scans for 10 participants recruited to the VoxTox study. The femoral
heads were used to produce a fixed point to which all rectal contours were
referenced. RESULTS: Sigma [standard deviation (SD) of means] between planning
and treatment was 4.2 mm in the anteroposterior (AP) direction and 1.3 mm left
right (LR). sigma (root mean square of SDs) was 5.2 mm AP and 2.7 mm LR. Superior
inferior variation was less than one slice above and below the planning position.
CONCLUSION: Our results for Sigma are in line with published data for prostate
motion. sigma, however, was approximately twice as great as that seen for
prostate motion. This suggests that DA may differ from planned dose in some
patients treated with radiotherapy for prostate cancer. ADVANCES IN KNOWLEDGE:
This work is the first to use daily imaging to quantify Sigma and sigma of the
rectum in prostate cancer. sigma was found to be greater than published data,
providing strong rationale for further investigation of individual DA.
PMID- 25138158
TI - The pathogenic mechanism of diabetes varies with the degree of overexpression and
oligomerization of human amylin in the pancreatic islet beta cells.
AB - The aggregation of human amylin (hA) to form cytotoxic structures has been
closely associated with the causation of type 2 diabetes. We sought to advance
understanding of how altered expression and aggregation of hA might link beta
cell degeneration with diabetes onset and progression, by comparing phenotypes
between homozygous and hemizygous hA-transgenic mice. The homozygous mice
displayed elevated islet hA that correlated positively with measures of oligomer
formation (r=0.91; P<0.0001). They also developed hyperinsulinemia with transient
insulin resistance during the prediabetes stage and then underwent rapid beta
cell loss, culminating in severe juvenile-onset diabetes. The prediabetes stage
was prolonged in the hemizygous mice, wherein beta-cell dysfunction and extensive
oligomer formation occurred in adulthood at a much later stage, when hA levels
were lower (r=-0.60; P<0.0001). This is the first report to show that hA-evoked
diabetes is associated with age, insulin resistance, progressive islet
dysfunction, and beta-cell apoptosis, which interact variably to cause the
different diabetes syndromes. The various levels of hA elevation cause different
extents of oligomer formation in the disease stages, thus eliciting early- or
adult-onset diabetes syndromes, reminiscent of type 1 and 2 diabetes,
respectively. Thus, the hA-evoked diabetes phenotypes differ substantively
according to degree of amylin overproduction. These findings are relevant to the
understanding of the pathogenesis and the development of experimental
therapeutics for diabetes.
PMID- 25138159
TI - The CAP1/Prss8 catalytic triad is not involved in PAR2 activation and protease
nexin-1 (PN-1) inhibition.
AB - Serine proteases, serine protease inhibitors, and protease-activated receptors
(PARs) are responsible for several human skin disorders characterized by impaired
epidermal permeability barrier function, desquamation, and inflammation. In this
study, we addressed the consequences of a catalytically dead serine protease on
epidermal homeostasis, the activation of PAR2 and the inhibition by the serine
protease inhibitor nexin-1. The catalytically inactive serine protease
CAP1/Prss8, when ectopically expressed in the mouse, retained the ability to
induce skin disorders as well as its catalytically active counterpart (75%,
n=81). Moreover, this phenotype was completely normalized in a PAR2-null
background, indicating that the effects mediated by the catalytically inactive
CAP1/Prss8 depend on PAR2 (95%, n=131). Finally, nexin-1 displayed analogous
inhibitory capacity on both wild-type and inactive mutant CAP1/Prss8 in vitro and
in vivo (64% n=151 vs. 89% n=109, respectively), indicating that the catalytic
site of CAP1/Prss8 is dispensable for nexin-1 inhibition. Our results demonstrate
a novel inhibitory interaction between CAP1/Prss8 and nexin-1, opening the search
for specific CAP1/Prss8 antagonists that are independent of its catalytic
activity.
PMID- 25138160
TI - Sumanenyl metallocenes: synthesis and structure of mono- and trinuclear
zirconocene complexes.
AB - Mono- and trinuclear sumanenyl zirconocene complexes Cp(sumanenyl)ZrCl2,
Cp*(sumanenyl)ZrCl2, and (C21H9)[(Cp*)ZrCl2]3 were successfully synthesized. In
the mononuclear complexes, convex binding with disturbed eta(5)-bonding was
confirmed in a solid state. As demonstrated in the trinuclear complex, the
multibenzylic anion of sumanene offers a novel ligand for the multinuclear
metallocenes.
PMID- 25138157
TI - Melanoma upregulates ICAM-1 expression on endothelial cells through engagement of
tumor CD44 with endothelial E-selectin and activation of a PKCalpha-p38-SP-1
pathway.
AB - Cancer metastasis involves multistep adhesive interactions between tumor cells
(TCs) and endothelial cells (ECs), but the molecular mechanisms of intercellular
communication in the tumor microenvironment remain elusive. Using static and flow
coculture systems in conjunction with flow cytometry, we discovered that certain
receptors on the ECs are upregulated on melanoma cell adhesion. Direct contact
but not separate coculture between human umbilical endothelial cells (HUVECs) and
a human melanoma cell line (Lu1205) increased intercellular adhesion molecule 1
(ICAM-1) and E-selectin expression on HUVECs by 3- and 1.5-fold, respectively,
compared with HUVECs alone. The nonmetastatic cell line WM35 failed to promote
ICAM-1 expression changes in HUVECs on contact. Enzyme-linked immunosorbent assay
(ELISA) revealed that EC-TC contact has a synergistic effect on the expression of
the cytokines interleukin (IL)-8, IL-6, and growth-related oncogene alpha (Gro
alpha). By using E-selectin cross-linking and beads coated with CD44
immunopurified from Lu1205 cells, we showed that CD44/selectin ligation was
responsible for the ICAM-1 up-regulation on HUVECs. Protein kinase Calpha (PKC
alpha) activation was found to be the downstream target of the CD44/selectin
initiated signaling, as ICAM-1 elevation was inhibited by siRNA targeting
PKCalpha or a dominant negative form of PKCalpha (PKCalpha DN). Western blot
analysis and electrophoretic mobility shift assays (EMSAs) showed that TC-EC
contact mediated p38 phosphorylation and binding of the transcription factor SP-1
to its regulation site. In conclusion, CD44/selectin binding signals ICAM-1 up
regulation on the EC surface through a PKCalpha-p38-SP-1 pathway, which further
enhances melanoma cell adhesion to ECs during metastasis.
PMID- 25138161
TI - Identification of essential histidine residues involved in heme binding and
Hemozoin formation in heme detoxification protein from Plasmodium falciparum.
AB - Malaria parasites digest hemoglobin within a food vacuole to supply amino acids,
releasing the toxic product heme. During the detoxification, toxic free heme is
converted into an insoluble crystalline form called hemozoin (Hz). Heme
detoxification protein (HDP) in Plasmodium falciparum is one of the most potent
of the hemozoin-producing enzymes. However, the reaction mechanisms of HDP are
poorly understood. We identified the active site residues in HDP using a
combination of Hz formation assay and spectroscopic characterization of mutant
proteins. Replacement of the critical histidine residues His122, His172, His175,
and His197 resulted in a reduction in the Hz formation activity to approximately
50% of the wild-type protein. Spectroscopic characterization of histidine
substituted mutants revealed that His122 binds heme and that His172 and His175
form a part of another heme-binding site. Our results show that the histidine
residues could be present in the individual active sites and could be ligated to
each heme. The interaction between heme and the histidine residues would serve as
a molecular tether, allowing the proper positioning of two hemes to enable heme
dimer formation. The heme dimer would act as a seed for the crystal growth of Hz
in P. falciparum.
PMID- 25138162
TI - The cost-effectiveness of infliximab in Crohn's disease.
AB - Crohn's disease (CD) is a chronic inflammatory condition that can affect any part
of the gastrointestinal tract. It leads to severe symptoms and reduced quality of
life. Infliximab is a monoclonal antibody against TNF-alpha and is effective in
treating moderate to severe CD. It is associated with high treatment costs, but
subsequent reductions in hospitalisation and surgery have been reported. This
review examines the evidence for the cost-effectiveness of infliximab for the
treatment of CD. Studies have been found to be very heterogeneous depending on
setting, costs assumed and clinical data. Within the UK setting infliximab has
been found to be cost effective with increased costs of around L25,000 per
quality adjusted life year gained.
PMID- 25138163
TI - Arterial pressure and flow wave analysis using time-domain 1-D hemodynamics.
AB - We reviewed existing methods for analyzing, in the time domain, physical
mechanisms underlying the patterns of blood pressure and flow waveforms in the
arterial system. These are wave intensity analysis and separations into several
types of waveforms: (i) forward- and backward-traveling, (ii) peripheral and
conduit, or (iii) reservoir and excess. We assessed the physical information
provided by each method and showed how to combine existing methods in order to
quantify contributions to numerically generated waveforms from previous cardiac
cycles and from specific regions and properties of the numerical domain: the
aortic root, arterial bifurcations and tapered vessels, peripheral reflection
sites, and the Windkessel function of the aorta. We illustrated our results with
numerical examples involving generalized arterial stiffening in a distributed one
dimensional model or localized changes in the model parameters due to a femoral
stenosis, carotid stent or abdominal aortic aneurysm.
PMID- 25138164
TI - Design and validation of a novel ferromagnetic bare metal stent capable of
capturing and retaining endothelial cells.
AB - Rapid healing of vascular stents is important for avoiding complications
associated with stent thrombosis, restenosis, and bleeding related to
antiplatelet drugs. Magnetic forces can be used to capture iron-labeled
endothelial cells immediately following stent implantation, thereby promoting
healing. This strategy requires the development of a magnetic stent that is
biocompatible and functional. We designed a stent from the weakly ferromagnetic
2205 stainless steel using finite element analysis. The final design exhibited a
principal strain below the fracture limit of 30% during crimping and expansion.
Ten stents were fabricated and validated experimentally for fracture resistance.
Another 10 stents magnetized with a neodymium magnet showed a magnetic field in
the range of 100-750 mG. The retained magnetism was sufficiently strong to
capture magnetically-labeled endothelial cells on the stent surfaces during in
vitro studies. Magnetically-labeled endothelial cell capture was also verified in
vivo after 7 days following coronary implantation in 4 pigs using histological
analysis. Images of the stented blood vessels showed uniform endothelium
formation on the stent surfaces. In conclusion, we have designed a ferromagnetic
bare metal stent from 2205 stainless steel that is functional, biocompatible, and
able to capture and retain magnetically-labeled endothelial cells in order to
promote rapid stent healing.
PMID- 25138166
TI - Improved amorphous/crystalline silicon interface passivation for heterojunction
solar cells by low-temperature chemical vapor deposition and post-annealing
treatment.
AB - In this study, hydrogenated amorphous silicon (a-Si:H) thin films are deposited
using a radio-frequency plasma-enhanced chemical vapor deposition (RF-PECVD)
system. The Si-H configuration of the a-Si:H/c-Si interface is regulated by
optimizing the deposition temperature and post-annealing duration to improve the
minority carrier lifetime (taueff) of a commercial Czochralski (Cz) silicon
wafer. The mechanism of this improvement involves saturation of the
microstructural defects with hydrogen evolved within the a-Si:H films due to the
transformation from SiH2 into SiH during the annealing process. The post
annealing temperature is controlled to ~180 degrees C so that silicon
heterojunction solar cells (SHJ) could be prepared without an additional
annealing step. To achieve better performance of the SHJ solar cells, we also
optimize the thickness of the a-Si:H passivation layer. Finally, complete SHJ
solar cells are fabricated using different temperatures for the a-Si:H film
deposition to study the influence of the deposition temperature on the solar cell
parameters. For the optimized a-Si:H deposition conditions, an efficiency of
18.41% is achieved on a textured Cz silicon wafer.
PMID- 25138165
TI - Change of direction in the biomechanics of atherosclerosis.
AB - The non-uniform distribution of atherosclerosis within the arterial system has
been attributed to pro-atherogenic influences of low, oscillatory haemodynamic
wall shear stress (WSS) on endothelial cells (EC). This theory is challenged by
the changes in lesion location that occur with age in human and rabbit aortas.
Furthermore, a number of point-wise comparisons of lesion prevalence and WSS have
failed to support it. Here we investigate the hypothesis that multidirectional
flow-characterized as the average magnitude of WSS components acting transversely
to the mean vector (transWSS)-plays a key role. Maps of lesion prevalence around
aortic branch ostia in immature and mature rabbits were compared with equivalent
maps of time average WSS, the OSI (an index characterizing oscillatory flow) and
transWSS, obtained from computational simulations; Spearman's rank correlation
coefficients were calculated for aggregated data and 95% confidence intervals
were obtained by bootstrapping methods. Lesion prevalence correlated positively,
strongly and significantly with transWSS at both ages. Correlations of lesion
prevalence with the other shear metrics were not significant or were
significantly lower than those obtained for transWSS. No correlation supported
the low, oscillatory WSS theory. The data are consistent with the view that
multidirectional near-wall flow is highly pro-atherogenic. Effects of
multidirectional flow on EC, and methods for investigating them, are reviewed.
The finding that oscillatory flow has pro-inflammatory effects when acting
perpendicularly to the long axis of EC but anti-inflammatory effects when acting
parallel to it may explain the stronger correlation of lesion prevalence with
transWSS than with the OSI.
PMID- 25138167
TI - Absence of amplification of the FGFR1-gene in human malignant mesothelioma of the
pleura: a pilot study.
AB - BACKGROUND: Mesothelioma (MPM) is a rare malignant disease with a worse outcome.
Fibroblast growth factor 1 (FGFR1) may be an interesting target for selective
tyrosine kinases inhibitors (TKI) in MPM. The aim of this study was to evaluate
the amplification of the FGFR1 gene in patients suffering from MPM. FINDINGS: We
identified nineteen male patients treated in our department between August 2008
and July 2010 matching the inclusion criteria. Mean age was 68 years.
Histopathological examination confirmed thirteen patients with epitheloid
subtype, five with biphasic and one patient with sarcomatoid. Fluorescence in
situ hybridization analysis revealed no polysomy nor an amplification of the FGFR
gene copy number in any case. CONCLUSION: Regarding that also EGFR amplifications
in MPM are absolute rarities, our findings may be a hint that TKI's will not
satisfy the hope for a new era in the treatment of MPM.
PMID- 25138168
TI - Comparative assembly hubs: web-accessible browsers for comparative genomics.
AB - MOTIVATION: Researchers now have access to large volumes of genome sequences for
comparative analysis, some generated by the plethora of public sequencing
projects and, increasingly, from individual efforts. It is not possible, or
necessarily desirable, that the public genome browsers attempt to curate all
these data. Instead, a wealth of powerful tools is emerging to empower users to
create their own visualizations and browsers. RESULTS: We introduce a pipeline to
easily generate collections of Web-accessible UCSC Genome Browsers interrelated
by an alignment. It is intended to democratize our comparative genomic browser
resources, serving the broad and growing community of evolutionary genomicists
and facilitating easy public sharing via the Internet. Using the alignment, all
annotations and the alignment itself can be efficiently viewed with reference to
any genome in the collection, symmetrically. A new, intelligently scaled
alignment display makes it simple to view all changes between the genomes at all
levels of resolution, from substitutions to complex structural rearrangements,
including duplications. To demonstrate this work, we create a comparative
assembly hub containing 57 Escherichia coli and 9 Shigella genomes and show
examples that highlight their unique biology. AVAILABILITY AND IMPLEMENTATION:
The source code is available as open source at:
https://github.com/glennhickey/progressiveCactus The E.coli and Shigella genome
hub is now a public hub listed on the UCSC browser public hubs Web page.
PMID- 25138169
TI - Pepper: cytoscape app for protein complex expansion using protein-protein
interaction networks.
AB - We introduce Pepper (Protein complex Expansion using Protein-Protein
intERactions), a Cytoscape app designed to identify protein complexes as densely
connected subnetworks from seed lists of proteins derived from proteomic studies.
Pepper identifies connected subgraph by using multi-objective optimization
involving two functions: (i) the coverage, a solution must contain as many
proteins from the seed as possible, (ii) the density, the proteins of a solution
must be as connected as possible, using only interactions from a proteome-wide
interaction network. Comparisons based on gold standard yeast and human datasets
showed Pepper's integrative approach as superior to standard protein complex
discovery methods. The visualization and interpretation of the results are
facilitated by an automated post-processing pipeline based on topological
analysis and data integration about the predicted complex proteins. Pepper is a
user-friendly tool that can be used to analyse any list of proteins.
AVAILABILITY: Pepper is available from the Cytoscape plug-in manager or online
(http://apps.cytoscape.org/apps/pepper) and released under GNU General Public
License version 3.
PMID- 25138170
TI - The difficulty in evaluating all findings in study on use of macrolides in mother
and child and risk of infantile hypertrophic pyloric stenosis.
PMID- 25138171
TI - Pertuzumab in combination with trastuzumab and docetaxel for the treatment of
HER2-positive metastatic or locally recurrent unresectable breast cancer.
AB - The National Institute for Health and Care Excellence (NICE) invited the
manufacturer of pertuzumab (Roche) to submit evidence for the clinical and cost
effectiveness of pertuzumab + trastuzumab + docetaxel for the treatment of human
epidermal growth factor receptor 2-positive (HER2+) metastatic or locally
recurrent unresectable breast cancer in accordance with the Institute's Single
Technology Appraisal (STA) process. The Liverpool Reviews and Implementation
Group (LRiG) at the University of Liverpool was commissioned to act as the
Evidence Review Group (ERG). This article summarises the ERG's review of the
evidence submitted by the manufacturer and provides a summary of the Appraisal
Committee's (AC) initial decision. At the time of writing, final guidance had not
been published by NICE. The clinical evidence was mainly derived from an ongoing
phase III randomised double-blind placebo-controlled international multicentre
clinical trial (CLEOPATRA), designed to evaluate efficacy and safety in 808
patients, which compared pertuzumab + trastuzumab + docetaxel (pertuzumab arm)
with placebo + trastuzumab + docetaxel (control arm). Both progression-free
survival (PFS) and overall survival (OS) were analysed at two data cut-off points
May 2011 (median follow-up of 18 months) and May 2012 (median follow-up of 30
months). At both time points, PFS was significantly longer in the pertuzumab arm
(18.5 months compared with 12.4 months in the control arm at the first data cut
off point and 18.7 versus 12.4 months at the second data cut-off point).
Assessment of OS benefit suggested an improvement for patients in the pertuzumab
arm with a strong trend towards an OS benefit at the second data cut-off point;
however, due to the immaturity of the OS data, the magnitude of the OS benefit
was uncertain. Importantly, cardiotoxicity was not increased in patients treated
with a combination of pertuzumab + trastuzumab + docetaxel. The ERG's main
concern with the clinical effectiveness data was the lack of mature OS data. An
additional concern of the AC was that the majority of patients in the randomised
controlled trial were trastuzumab naive, which does not reflect current clinical
practice. The incremental cost-effectiveness ratios (ICERs) generated by the
manufacturer's model are considered to be commercial in confidence data and
therefore cannot be published. Nevertheless, the results of the manufacturer's
probabilistic sensitivity analyses suggest that pertuzumab + trastuzumab +
docetaxel has a 0 % probability of being cost effective at a willingness-to-pay
of L30,000 per quality-adjusted life-year gained when compared with trastuzumab +
docetaxel. The ERG believes that more realistic estimates of the ICERs are
considerably higher, almost double those presented by the manufacturer. This is
because the ERG believes that due to the manner in which the economic model is
constructed, the additional survival benefit following disease progression that
is generated for patients treated with pemetrexed + trastuzumab + docetaxel is
unrealistic. At the time of writing, NICE had not made a final decision regarding
this technology but had instead referred the issue of the assessment of
technologies that are not effective at a zero price to their Decision Support
Unit for advice.
PMID- 25138172
TI - Associations of socioeconomic position and pain prevalence in the United States:
findings from the National Health and Nutrition Examination Survey.
AB - BACKGROUND: Pain is a significant burden within the U.S. adult population, but
little is known regarding epidemiology of pain, particularly with respect to
race, ethnicity, and socioeconomic position (SEP). OBJECTIVE: The purpose of this
study was to describe and evaluate prevalence and distribution of pain in the
United States. METHODS: With data from the population-based 2003-2004 National
Health and Nutrition Examination Survey, prevalence of acute (<3 months) and
chronic (>= 3 months) pain was evaluated, including subgroup analyses of race,
ethnicity, and SEP, with SEP defined by the poverty-to-income ratio, a ratio
derived from the federal poverty level, accounting for household income and
number of household members. RESULTS: Prevalence of acute pain was 12.2% (95%
confidence interval: 11.2-13.3%). Non-Hispanic black as well as Hispanic and
Mexican-American individuals had higher rates of acute pain than non-Hispanic
white people, and a higher prevalence was noted in those with higher SEP. Chronic
pain prevalence was 15.6% (13.4-17.7%), with non-Hispanic white people having a
higher prevalence than those in other racial and ethnic groups. CONCLUSION:
Trends of chronic pain by SEP were opposite of acute pain as those in the highest
SEP group tended to have less chronic pain than those in lower SEP groups. These
findings suggest that SEP, in addition to race and ethnicity, may play a role in
the development of pain as well as its treatment and management.
PMID- 25138173
TI - Deferasirox for iron chelation in multitransfused children with sickle cell
disease; long-term experience in the East London clinical haemoglobinopathy
network.
AB - Deferasirox (DFX) has been licensed for iron chelation in patients with sickle
cell disease (SCD), but there is limited data on its long-term efficacy and
safety in children. This retrospective study included 62 regularly transfused
children managed in the East London and Essex Clinical Haemoglobinopathy Network
(mean age 9.2 +/- 3.2 yr). Efficacy measurements consisted of monthly serum
ferritin (SF) and annual R2 MRI-estimated liver iron concentration (LIC), and
safety markers included serum creatinine and alanine aminotransferase (ALT). The
mean duration of DFX treatment was 2.5 +/- 1.4 yr, and mean dose at 36 months was
25 mg/kg/d. Mean SF at initiation of treatment was 2542 +/- 952 ng/mL and
increased to 4691 +/- 2255 ng/mL at 36 months (P = 0.05). Mean LIC on first scan
was 10.3 mg/g dry weight and did not decrease significantly on follow-up scans.
There was a significant correlation between relative change in LIC and in SF
(R(2) = 0.66, P < 0.001). Reversible transaminitis episodes, probably due to drug
induced hepatitis, were noted in 53% of patients. Responses to an adherence and
acceptability questionnaire indicated that more than 50% of children had
difficulties in taking DFX, commonly because of unpleasant taste. Our results
show that more than 50% of children with SCD have inadequate control of iron
overload with DFX. It is not clear whether this is because of frequent dose
interruptions, poor tolerability and adherence, or poor efficacy of the drug. We
recommend further studies to confirm these findings and to optimise iron
chelation in this population.
PMID- 25138174
TI - Do mixotrophs grow as photoheterotrophs? Photophysiological acclimation of the
chrysophyte Ochromonas danica after feeding.
AB - Mixotrophy is increasingly recognized as an important and widespread nutritional
strategy in various taxonomic groups ranging from protists to higher plants. We
hypothesize that the availability of alternative carbon and energy sources during
mixotrophy allows a switch to photoheterotrophic growth, where the photosynthetic
apparatus mainly provides energy but not fixed carbon. Because such a change in
the function of the photosynthetic machinery is probably reflected in its
composition, we compared the photosynthetic machinery in Ochromonas danica during
autotrophic and mixotrophic growth. Compared with autotrophic growth, the total
pigmentation of O. danica was reduced during mixotrophic growth. Furthermore, the
photosystem I (PSI):PSII ratio increased, and the cellular content of Rubisco
decreased not only absolutely, but also relative to the content of PSII. The
changing composition of the photosynthetic apparatus indicates a shift in its
function from providing both carbon and energy during photoautotrophy to mainly
providing energy during mixotrophy. This preference for photoheterotrophic growth
has interesting implications for the contribution of mixotrophic species to
carbon cycling in diverse ecosystems.
PMID- 25138175
TI - Potentiation of the in vitro antistaphylococcal effect of oxacillin and
tetracycline by the anti-inflammatory drug diacetyl rhein.
AB - BACKGROUND: The anti-inflammatory drug diacetyl rhein has been found to possess
promising antistaphylococcal effects against various drug-resistant strains in
our previous study. In the present work, we explored the in vitro combinatory
interactions of diacetyl rhein with oxacillin and tetracycline against 13
standard strains and clinical isolates of Staphylococcus aureus, including those
resistant to erythromycin, methicillin and tetracycline. METHODS: Minimum
inhibitory concentrations were determined by broth microdilution assay, and the
effects of combinations were evaluated according to the sum of fractional
inhibitory concentrations (SigmaFICs). RESULTS: Synergistic or additive effects
were observed against all S. aureus strains (SigmaFIC 0.258-1), whereas diacetyl
rhein-oxacillin appeared to be the most effective combination, synergistically
inhibiting the growth of 4 strains tested. CONCLUSION: To our best knowledge,
this is the first report on a synergistic antibacterial effect of diacetyl rhein.
Our results suggest this promising compound for further evaluation of its
synergistic anti-infective potential as an agent with a combined anti
inflammatory and synergistic antibacterial action.
PMID- 25138176
TI - CYP-13A12 of the nematode Caenorhabditis elegans is a PUFA-epoxygenase involved
in behavioural response to reoxygenation.
AB - A specific behavioural response of Caenorhabditis elegans, the rapid increase of
locomotion in response to anoxia/reoxygenation called the O2-ON response, has
been used to model key aspects of ischaemia/reperfusion injury. A genetic
suppressor screen demonstrated a direct causal role of CYP (cytochrome P450)
13A12 in this response and suggested that CYP-eicosanoids, which in mammals
influence the contractility of cardiomyocytes and vascular smooth muscle cells,
might function in C. elegans as specific regulators of the body muscle cell
activity. In the present study we show that co-expression of CYP-13A12 with the
NADPH-CYP-reductase EMB-8 in insect cells resulted in the reconstitution of an
active microsomal mono-oxygenase system that metabolized EPA (eicosapentaenoic
acid) and also AA (arachidonic acid) to specific sets of regioisomeric epoxy and
hydroxy derivatives. The main products included 17,18-EEQ (17,18
epoxyeicosatetraenoic acid) from EPA and 14,15-EET (14,15-epoxyeicosatrienoic
acid) from AA. Locomotion assays showed that the defective O2-ON response of C20
PUFA (polyunsaturated fatty acid)-deficient, Delta-12 and Delta-6 fatty acid
desaturase mutants (fat-2 and fat-3 respectively) can be restored by feeding the
nematodes AA or EPA, but not ETYA (eicosatetraynoic acid), a non-metabolizable AA
analogue. Short-term incubation with 17,18-EEQ was sufficient to rescue the
impaired locomotion of the fat-3 strain. The endogenous level of free 17,18-EEQ
declined during anoxia and was rapidly restored in response to reoxygenation. On
the basis of these results, we suggest that CYP-dependent eicosanoids such as
17,18-EEQ function as signalling molecules in the regulation of the O2-ON
response in C. elegans. Remarkably, the exogenously administered 17,18-EEQ
increased the locomotion activity under normoxic conditions and was effective not
only with C20-PUFA-deficient mutants, but to a lesser extent also with wild-type
worms.
PMID- 25138177
TI - Innovations: resetting our thinking to solve problems.
PMID- 25138178
TI - SEDUCEd by optical coherence tomography in drug-eluting balloon assessment.
PMID- 25138179
TI - Lessons from acute and late scaffold failures in the ABSORB EXTEND trial: have we
really learned them all?
PMID- 25138180
TI - Emerging strategies for rapid reversal of anticoagulation in patients undergoing
catheter-based interventions: aptamers enter the RADAR.
PMID- 25138182
TI - Optical coherence tomography study of healing characteristics of paclitaxel
eluting balloons vs. everolimus-eluting stents for in-stent restenosis: the
SEDUCE (Safety and Efficacy of a Drug elUting balloon in Coronary artery
rEstenosis) randomised clinical trial.
AB - AIMS: Little is known about the respective healing responses and clinical
efficacy and safety of drug-eluting balloons (DEB) and the second generation of
drug-eluting stents (DES) when used to treat in-stent restenosis (ISR). In this
study, we set out to compare prospectively the healing characteristics, as
assessed by optical coherence tomography (OCT), of DEB versus DES after treatment
of ISR in bare metal stents (BMS). METHODS AND RESULTS: Fifty patients with BMS
ISR were randomised to treatment with a paclitaxel-eluting balloon vs. an
everolimus-eluting stent (EES). The primary endpoint was the percentage of
uncovered struts, assessed with OCT at nine months, as a marker of vessel wall
healing. A mean of 366+/-135 and 636+/-184 struts were analysed per patient in
the DEB and EES groups, respectively. The percentage of uncovered struts per
patient was significantly lower with DEB vs. EES (1.4% vs. 3.1%, p=0.025). Mean
neointimal hyperplasia area was 2.4+/-1.08 mm in DEB vs. 1.92+/-0.67 mm in EES
(p=0.1806), while the percentage of malapposed struts per patient was very low in
both groups (0.2% vs. 0.3%, p=0.699). At nine months, angiographic in-stent MLD
(minimum lumen diameter) was lower (2.13 vs. 2.54 mm, p=0.006), while diameter
stenosis (26.4 vs. 11.4%, p=0.002), and LLL (0.28 vs. 0.07 mm, p=0.1) were higher
after DEB compared to EES. During one-year follow-up, we did not observe
differences in the rates of death, TLR (target lesion revascularisation) or stent
thrombosis. CONCLUSIONS: DEB appears to be associated with better healing
characteristics, as assessed by stent strut coverage with OCT, but tended to be
slightly less effective compared to EES. These findings give support to the use
of either DEB or EES as valuable treatment options for ISR. CLINICAL TRIAL
REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT 01065532.
PMID- 25138183
TI - Comparison of bivalirudin and heparin in patients undergoing rotational
atherectomy: a subanalysis of the randomised ROTAXUS trial.
AB - AIMS: Bivalirudin has emerged as a meaningful alternative to heparin in patients
undergoing percutaneous coronary intervention (PCI). To date, it is unclear
whether bivalirudin has advantages in patients undergoing rotational atherectomy
(RA). METHODS AND RESULTS: The current subgroup analysis of the ROTAXUS trial
compared patients receiving bivalirudin (n=129) to those receiving unfractionated
heparin (UFH) (n=111). Efficacy was assessed by the frequency of periprocedural
myocardial infarction (MI) and safety by the frequency of major access-site
bleeding (ASB). Baseline characteristics were similar. Periprocedural MI occurred
less frequently in the bivalirudin group (22% vs. 37.5%, p=0.02), while ASB did
not differ significantly (2.3% vs. 5.5%, p=0.20). This effect was larger in the
RA group, where bivalirudin significantly reduced periprocedural MI (15.7% vs.
38.7%, p=0.01) with a trend towards reduced major ASB (2.9% vs. 10.2%, p=0.09).
In the control group without RA, bivalirudin was not superior to UFH regarding
periprocedural MI (28.6% vs. 36.6%, p=0.42) and major ASB (1.7% vs. 1.7%,
p=0.99). CONCLUSIONS: This analysis suggests a differential benefit of
bivalirudin in patients treated with RA. Patients receiving bivalirudin during RA
showed significantly less periprocedural MI and fewer ASB compared to patients
treated with UFH.
PMID- 25138184
TI - ST peak during percutaneous coronary intervention serves as an early prognostic
predictor in patients with ST-segment elevation myocardial.
AB - AIMS: To evaluate the clinical importance of the ST peak phenomenon during
primary percutaneous coronary intervention (PCI) in patients with ST-segment
elevation myocardial infarction (STEMI). METHODS AND RESULTS: Continuous ST
monitoring was performed in 942 STEMI patients from arrival until 90 minutes
after revascularisation. ST peak was defined as >=1 mm increase in the ST-segment
during PCI compared with the ST elevation before intervention. ST peak was
observed in 26.9% of patients. During median follow-up of 4.1 years, 20.7% of
patients experienced a major adverse cardiac event (MACE). ST peak was associated
with higher rates of mortality (13.4% versus 9.3%; p=0.044), admission for heart
failure (10.6% versus 5.2%; p=0.002) and MACE (26.9% versus 18.2%; p=0.002), but
not reinfarction (7.1% versus 5.2%; p=0.14). In two different Cox regression
analyses, adjusting for predictors of MACE and ST peak including ST resolution
and epicardial flow, ST peak remained significantly associated with MACE:
adjusted hazard ratio (HR) 1.40 (95% confidence interval [CI] 1.01-1.95) and 1.41
(95% CI: 1.02-1.96). CONCLUSIONS: In the largest study hitherto evaluating the ST
peak phenomenon during primary PCI, we demonstrated that ST peak is a strong
predictor of adverse long-term outcome and provides independent prognostic
information beyond that provided by ST resolution and epicardial flow.
PMID- 25138185
TI - Serial intravascular ultrasound observations from the Tryton first-in-man study.
AB - AIMS: To report serial intravascular ultrasound (IVUS) findings of bifurcation
lesions treated with the dedicated Tryton Side Branch Stent to assess mechanisms
of restenosis. METHODS AND RESULTS: The Tryton FIM study was a multicentre,
prospective, single-arm, "first-in-man" study to treat de novo bifurcation
lesions. Minimum lumen area (MLA) sites and overall volumes were analysed within
main vessels and side branches. Overall, 27 main vessels and 22 side branches had
paired baseline and follow-up IVUS. The post-intervention main vessel MLA
decreased from 5.3 (4.1, 6.2) to 4.8 (3.4, 5.7) mm2 at follow-up, p=0.02, and the
side branch MLA decreased from 3.5 (3.0, 3.8) to 2.5 (2.2, 3.2) mm2, p=0.0005.
Stent area at the side branch did not change (mean stent area from 4.0 [3.3, 4.1]
to 3.8 [3.4, 4.2] mm3/mm, p=0.95). Neointimal hyperplasia (NIH) net volume
obstruction (%) measured 1.8% (0.5, 7.0) for the entire main vessel and 14.9%
(2.3, 31.1) for the entire side branch stents. In both main vessel and side
branches the decrease in lumen area correlated significantly with NIH.
CONCLUSIONS: Serial IVUS analysis of a new side branch Tryton stent showed no
chronic stent recoil. Side branch underexpansion was common and along with
superimposed NIH contributed to the reduction in lumen dimensions at follow-up.
PMID- 25138186
TI - A rare cause of transient ischaemic attack in a young man: cardiac papillary
fibroelastoma.
PMID- 25138187
TI - Left atrial appendage closure for stroke prevention in non-valvular atrial
fibrillation: rationale, devices in clinical development and insights into
implantation techniques.
AB - AIMS: In patients with atrial fibrillation, a relevant stroke risk (CHA2DS2-VASc
score >=2) and a relative or absolute contraindication for oral anticoagulation,
catheter-based LAA occlusion is performed increasingly in Europe. The present
article summarises the rationale, clinical data, devices, implantation techniques
and follow-up drug regimens. METHODS AND RESULTS: European survey data on
patients with atrial fibrillation support the need for non-pharmacological
approaches for stroke prevention in patients with atrial fibrillation. A relevant
bleeding risk remains with novel oral anticoagulants (NOACs), which are also
dependent on drug compliance. Recent long-term data from the PROTECT-AF trial and
the CAP registry regarding the WATCHMAN LAA occluder device suggest safety and
efficacy. First registry data support the safety of two other CE-marked devices,
the AMPLATZER Cardiac Plug (ACP) and the Coherex WaveCrest device, which have
become available in Europe. Other LAA occlusion devices are in clinical
development. CONCLUSIONS: Catheter-based LAA occlusion is now being developed
further as an interventional approach for stroke prevention in patients with
atrial fibrillation. Implantation techniques and devices are being improved,
which will probably result in better procedural safety. Appropriate operator
training is of major importance for this approach.
PMID- 25138188
TI - Percutaneous closure of ruptured sinus of Valsalva aneurysm: results from a
multicentre experience.
AB - AIMS: To evaluate the safety and efficacy of percutaneous closure (PC) using
modified double-disc ventricular septal defect (VSD) occluders in patients with
ruptured sinus of Valsalva aneurysm (RSVA). METHODS AND RESULTS: Between 2005 and
2012, 25 patients were enrolled in our study for attempted PC. There were five
patients (20%) with RSVA combined with VSD and two (8%) with aortic regurgitation
(AR). The median age was 45 years (24-74 years). The QP/QS was 2.4+/-0.6 (1.6
4.0). The median diameter of lesions was 6 mm (4-8 mm) while the median size of
occluders was 8 mm (6-12 mm). Twenty-three patients (92%) underwent PC
successfully. Occluders were retrieved in two patients within one week. Trivial
residual shunts developed in three and mild occluder-related AR occurred in five
at discharge. During a median follow-up of 19 months (6-96 months) all trivial
residual shunts vanished and mild occluder-related AR disappeared in four out of
five patients. The proportion of patients in NYHA Class III/IV was reduced from
72% at baseline to 12% at the time of last follow-up (p<0.001). CONCLUSIONS: In
selected patients with RSVA, PC using modified double-disc occluders may become a
valuable alternative to surgery with encouraging immediate outcomes and midterm
results.
PMID- 25138189
TI - Distal embolisation during carotid stenting is predicted by circulating levels of
LDL cholesterol and C-reactive protein.
AB - AIMS: Distal embolisation during carotid artery stenting (CAS) is the main cause
of cerebral complications; thus, the amount of embolisation occurring during CAS
can be considered as a surrogate endpoint of cerebral complications. Our aim was
to find patient characteristics which are associated with a higher risk of
embolisation during CAS. METHODS AND RESULTS: From January to December 2010 all
consecutive patients undergoing CAS with embolic protection at three medium- to
high-volume Italian centres were prospectively enrolled in this multicentre
study. After CAS, the embolic debris was classified by visual inspection into two
groups: "scarce" (no debris or hardly visible debris), and "relevant" (visible
embolic debris) embolisation. Two hundred and thirty-six consecutive patients
(79% males, 32.7% symptomatic) were enrolled. Open cell stents were used in 52.7%
of the patients, distal filters were employed in 85.5% and proximal protection in
14.5%. Procedural success was achieved in 100% of procedures. Relevant
embolisation was observed in 16.1% of patients, including those who suffered all
the periprocedural complications (4.2%). At multivariate statistical analysis,
high circulating LDL cholesterol and C-reactive protein levels were the only
factors associated with relevant embolisation. CONCLUSIONS: In this study, high
circulating LDL cholesterol and C-reactive protein levels were associated with
relevant embolisation after CAS, opening up the hypothesis that therapy with
statins before elective CAS may reduce plaque embolisation and improve outcome.
(EudraCT number: 016737-95).
PMID- 25138190
TI - Balloon pulmonary angioplasty: an additional treatment option to improve the
prognosis of patients with chronic thromboembolic pulmonary hypertension.
AB - AIMS: To evaluate the efficacy and safety of balloon pulmonary angioplasty (BPA)
in patients with non-operable chronic thromboembolic pulmonary hypertension
(CTEPH) using the results of pulmonary endarterectomy (PEA) for operable patients
as a reference, and annotate the role of BPA in the management of CTEPH. METHODS
AND RESULTS: Data from 53 CTEPH patients were collected retrospectively. Twenty
four operable patients underwent PEA, and 29 non-operable patients underwent BPA.
Patients who underwent BPA showed improved mean pulmonary arterial pressure,
pulmonary vascular resistance, and cardiac output (39.4+/-6.9 to 21.3+/-5.6 mmHg,
763+/-308 to 284+/-128 dyn.s-1.cm-5, 3.47+/-0.80 to 4.26+/-1.15 L/min,
respectively); patients who received PEA showed similar efficacy (44.4+/-11.0 to
21.6+/-6.7 mmHg, 781+/-278 to 258+/-125 dyn.s-1.cm-5, 3.35+/-1.11 to 4.44+/-1.58
L/min, respectively). The mortality rates of BPA and PEA patients were 3.4% and
8.3%, respectively. CONCLUSIONS: The efficacy and safety of BPA for non-operable
cases were similar to those achieved using PEA for operable cases. BPA could be
an additional treatment option for non-operable CTEPH patients, and most CTEPH
patients can be satisfactorily treated by BPA or PEA.
PMID- 25138191
TI - Tools & Techniques - statistics: non-inferiority trials.
PMID- 25138192
TI - How should I treat an undeployed stent stuck in the proximal LAD? Going for
another round...
PMID- 25138193
TI - The use of radial access decreases the risk of vascular access-site-related
complications at a patient level but is associated with an increased risk at a
population level: the radial paradox.
PMID- 25138194
TI - Phylogenetic analysis of barley WRKY proteins and characterization of HvWRKY1 and
-2 as repressors of the pathogen-inducible gene HvGER4c.
AB - The WRKY transcription factors belong to an evolutionarily conserved superprotein
family predominantly present in the plant kingdom. WRKY proteins of barley are
not yet fully annotated and most of them are not functionally characterized. We
performed a genome-wide identification of WRKY members based on the recently
accessible barley draft genome sequence and full-length cDNA datasets. As a
result, 34 novel putative proteins have been identified which extend the existing
list for barley WRKYs to 94. Phylogenetic analysis of the WRKY domains allowed
ranking into three groups (I, II, III), with an expansion in group III in
monocots. Two members of subgroup IIa, the wound and pathogen-inducible HvWRKY1
and HvWRKY2, are known as negative defense regulators. Here, we demonstrate that
both transcription factors repress the activity of the powdery mildew-induced
promoter of HvGER4c, a germin-like defense-related protein. The repression did
not require the negative defense regulator MLO nor was it affected by the
presence of the R protein MLA12. Moreover, the expression of the Arabidopsis
ortholog AtWRKY40 in barley compromised basal resistance to powdery mildew,
providing evidence for functional conservation of sequence-related WRKY proteins
across monocots and dicots.
PMID- 25138196
TI - Policy brief. Do unemployed women give birth to infants with higher rates of
infant mortality and low birthweight?
PMID- 25138197
TI - Does "Out of work" get into the womb? Exploring the relationship between
unemployment and adverse birth outcomes.
AB - This study uses Texas vital records from 1994 to 2003 to examine the relationship
between self-reported maternal unemployment and birth outcomes, including
birthweight and infant mortality. In the preferred specification, a sample
containing 1,344, 605 sibling births to 604,649 mothers was used. Regression
results indicated that within the same women, being unemployed was associated
with lower average birthweights and higher rates of infant mortality than being
engaged in market work, especially when unemployment preceded market work, and a
range of hypothesized mediators did little to attenuate these relationships.
Interaction models revealed that the poor average birth outcomes related to
unemployment were driven by observations with at least one other indicator of
health complication, such as presence of a medical risk factor. These results
confirm that the relationship between unemployment and mother-child health varies
across individuals, although further research is needed to understand the causal
linkages connecting unemployment, health risks, and birth outcomes.
PMID- 25138195
TI - Effectiveness of individual placement and support supported employment for young
adults.
AB - AIM: The individual placement and support (IPS) model of supported employment was
first developed in community mental health centres for adults with severe mental
illness. While IPS is an established evidence-based practice in this broad
population, evidence on its effectiveness focused specifically on young adults
has been limited. The current study aimed to address this gap. METHODS: To
investigate the effects of IPS on young adults, the authors conducted a secondary
analysis on a pooled sample of 109 unemployed young adults (under age 30) from
four randomized controlled trials employing a common research protocol that
included a standardized measurement battery and rigorous fidelity monitoring.
Researchers assessed these participants over 18 months on nine competitive
employment outcome measures. RESULTS: On all measures, the IPS group had
significantly better employment outcomes. Overall, 40 (82%) of IPS participants
obtained employment during follow-up compared with 25 (42%) of control
participants, chi(2) = 17.9, P < .001. IPS participants averaged 25.0 weeks of
employment, compared with 7.0 weeks for control participants, t = 4.50, P < .001.
CONCLUSIONS: The current analysis supports a small number of previous studies in
showing that IPS is highly effective in helping young adults with severe mental
illness to attain competitive employment. When young adults acquire competitive
jobs and initiate a path towards normal adult roles, they may avoid the cycle of
disability and psychiatric patient roles that are demeaning and demoralizing.
PMID- 25138199
TI - Stress proliferation across generations? Examining the relationship between
parental incarceration and childhood health.
AB - Stress proliferation theory suggests that parental incarceration may have
deleterious intergenerational health consequences. In this study, I use data from
the 2011-2012 National Survey of Children's Health (NSCH) to estimate the
relationship between parental incarceration and children's fair or poor overall
health, a range of physical and mental health conditions, activity limitations,
and chronic school absence. Descriptive statistics show that children of
incarcerated parents are a vulnerable population who experience disadvantages
across an array of health outcomes. After adjusting for demographic,
socioeconomic, and familial characteristics, I find that parental incarceration
is independently associated with learning disabilities, attention deficit
disorder and attention deficit hyperactivity disorder, behavioral or conduct
problems, developmental delays, and speech or language problems. Taken together,
results suggest that children's health disadvantages are an overlooked and
unintended consequence of mass incarceration and that incarceration, given its
unequal distribution across the population, may have implications for population
level racial-ethnic and social class inequalities in children's health.
PMID- 25138198
TI - Gender and reinforcing associations between socioeconomic disadvantage and body
mass over the life course.
AB - Using the 1957-1993 data from the Wisconsin Longitudinal Study, we explore
reciprocal associations between socioeconomic status (SES) and body mass in the
1939 birth cohort of non-Hispanic white men and women. We integrate the
fundamental cause theory, the gender relations theory, and the life course
perspective to analyze gender differences in (a) the ways that early
socioeconomic disadvantage launches bidirectional associations of body mass and
SES and (b) the extent to which these mutually reinforcing effects generate
socioeconomic disparities in midlife body mass. Using structural equation
modeling, we find that socioeconomic disadvantage at age 18 is related to higher
body mass index and a greater risk of obesity at age 54, and that this
relationship is significantly stronger for women than men. Moreover, women are
more adversely affected by two mechanisms underlying the focal association: the
obesogenic effect of socioeconomic disadvantage and the SES-impeding effect of
obesity. These patterns were also replicated in propensity score-matching models.
We conclude that gender and SES act synergistically over the life course to shape
reciprocal chains of two disadvantaged statuses: heavier body mass and lower SES.
PMID- 25138201
TI - "I want you to save my kid!": Illness management strategies, access, and
inequality at an elite university research hospital.
AB - Using data drawn from interviews and observations with 18 families whose children
were diagnosed with life-threatening, often rare diseases, I examine how families
accessed and negotiated medical care at a top 10-ranked university research
hospital. Access to highly specialized and technologically advanced care was
essential in these critical cases. Combining analysis of these high-stakes cases
with recent work highlighting the interactional dynamics of care delivery, I show
how families followed different paths to elite care and used different illness
management strategies throughout the treatment process depending on their ability
to mobilize what Janet Shim terms cultural health capital. These diverging
illness management strategies reproduced inequality even at the top of the U.S.
healthcare system by allowing some families to secure microadvantages throughout
the illness experience. These findings suggest a complex interplay between
structures of care delivery and families' illness management strategies and point
to the need for broader conceptualizations of healthcare advantages.
PMID- 25138200
TI - How health conditions translate into self-ratings: a comparative study of older
adults across Europe.
AB - Using data from the Survey of Health, Ageing and Retirement in Europe, we examine
how respondents translate morbidity and disability into self-rated health (SRH),
how national populations differ in SRH, and how normative and person-specific
reporting styles shape SRH. We construct proxy variables that allow us to specify
cultural differences in reporting styles and individual differences in relative
rating behavior. Using generalized logistic regression, we find that both of
these dimensions of subjectivity are related to SRH; however, their inclusion
does not significantly alter the connection between SRH and the set of disease
and disability indicators. Further, country differences in SRH persist after
controlling for all these factors. Our findings suggest that observed country
differences in SRH reflect compositional differences, cultural differences in
reporting styles, and perceptions of how health restricts typical activities. SRH
also seems to capture underlying but unmeasured health differences across
populations.
PMID- 25138202
TI - Spillover effects of an uninsured population.
AB - A lack of health insurance has long been associated with negative effects on
individual and family health due to access barriers. However, we know little
about how a lack of health insurance affects wider communities beyond health
care. Based on in-depth interviews in two Los Angeles communities, we report how
a lack of health insurance affects the functioning of religious institutions and
schools from kindergarten to 12th grade. We find a negative spillover effect at
the individual and institutional levels for schools experiencing greater
absenteeism due to health insurance problems of pupils. However, we find that
religious organizations are little affected by a lack of health insurance of
adherents. Instead, churches offer health programs as a means to engage their
communities. Besides documenting a negative and a positive spillover effect, we
offer a conceptual framework for the qualitative study of health spillover
effects and examine the policy implications of our findings.
PMID- 25138203
TI - Influence of distinct asthma phenotypes on lung function following weight loss in
the obese.
AB - BACKGROUND AND OBJECTIVE: There appears to be two distinct clinical phenotypes of
obese patients with asthma-those with early-onset asthma and high serum IgE (TH2
high), and those with late-onset asthma and low serum IgE (TH2-low). The aim of
the present study was to determine in the two phenotypes of obese asthma the
effect of weight loss on small airway function. METHODS: TH2-low (n = 8) and TH2
high (n = 5) obese asthmatics underwent methacholine challenge before and 12
months following bariatric surgery. Dose-response slopes as measures of
sensitivity to airway closure and narrowing were measured as maximum % fall
forced vital capacity (FVC) and forced expiratory volume in 1 s/FVC,
respectively, divided by dose. Resting airway mechanics were measured by forced
oscillation technique. RESULTS: Weight loss reduced sensitivity to airway closure
in TH 2-low but not TH2-high obese asthmatics (pre-post mean change +/- 95%
confidence interval: 1.8 +/- 0.8 doubling doses vs -0.3 +/- 1.7 doubling doses, P
= 0.04). However, there was no effect of weight loss on the sensitivity to airway
narrowing in either group (P = 0.8, TH2-low: 0.8 +/- 1.0 doubling doses, TH2
high: -1.1 +/- 2.5 doubling doses). In contrast, respiratory resistance (20 Hz)
improved in TH2-high but not in TH2-low obese asthmatics (pre-post change median
interquartile range: 1.5 (1.3-2.8) cmH2O/L/s vs 0.6 (-1.8-0.8) cmH2O/L/s, P =
0.03). CONCLUSIONS: TH2-low obese asthmatics appear to be characterized by
increased small airway responsiveness and abnormalities in resting airway
function that may persist following weight loss. However, this was not the case
for TH2-high obese asthmatics, highlighting the complex interplay between IgE
status and asthma pathophysiology in obesity.
PMID- 25138207
TI - Hospice Comics: Representations of Patient and Family Experience of Illness and
Death in Graphic Novels.
AB - Non-fiction graphic novels about illness and death created by patients and their
loved ones have much to teach all readers. However, the bond of empathy made
possible in the comic form may have special lessons for healthcare providers who
read these texts and are open to the insights they provide.
PMID- 25138208
TI - Label-free detection of serum proteins using surface-enhanced Raman spectroscopy
for colorectal cancer screening.
AB - Surface-enhanced Raman scattering (SERS) spectra of serum proteins purified from
human serum samples were employed to detect colorectal cancer. Acetic acid as a
new aggregating agent was introduced to increase the magnitude of the SERS
enhancement. High-quality SERS spectra of serum proteins were acquired from 103
cancer patients and 103 healthy volunteers. Tentative assignments of SERS bands
reflect that some specific biomolecular contents and protein secondary structures
change with colorectal cancer progression. Principal component analysis combined
with linear discriminant analysis was used to assess the capability of this
approach for identifying colorectal cancer, yielding diagnostic accuracies of
100% (sensitivity: 100%; specificity: 100%) based on albumin SERS spectroscopy
and 99.5% (sensitivity: 100%; specificity: 99%) based on globulin SERS
spectroscopy, respectively. A partial least squares (PLS) approach was introduced
to develop diagnostic models. An albumin PLS model successfully predicted the
unidentified subjects with a diagnostic accuracy of 93.5% (sensitivity: 95.6%;
specificity: 91.3%) and the globulin PLS model gave a diagnostic accuracy of
93.5% (sensitivity: 91.3%; specificity: 95.6%). These results suggest that serum
protein SERS spectroscopy can be a sensitive and clinically powerful means for
colorectal cancer detection.
PMID- 25138206
TI - Impact of medical and psychiatric multi-morbidity on mortality in diabetes:
emerging evidence.
AB - BACKGROUND: Multi-morbidity, or the presence of multiple chronic diseases, is a
major problem in clinical care and is associated with worse outcomes.
Additionally, the presence of mental health conditions, such as depression,
anxiety, etc., has further negative impact on clinical outcomes. However, most
health systems are generally configured for management of individual diseases
instead of multi-morbidity. The study examined the prevalence and differential
impact of medical and psychiatric multi-morbidity on risk of death in adults with
diabetes. METHODS: A national cohort of 625,903 veterans with type 2 diabetes was
created by linking multiple patient and administrative files from 2002 through
2006. The main outcome was time to death. Primary independent variables were
numbers of medical and psychiatric comorbidities over the study period.
Covariates included age, gender, race/ethnicity, marital status, area of
residence, service connection, and geographic region. Cox regression was used to
model the association between time to death and multi-morbidity adjusting for
relevant covariates. RESULTS: Hypertension (78%) and depression (13%) were the
most prevalent medical and psychiatric comorbidities, respectively; 23% had 3+
medical comorbidities, 3% had 2+ psychiatric comorbidities and 22% died. Among
medical comorbidities, mortality risk was highest in those with congestive heart
failure (hazard ratio, HR = 1.92; 95% CI 1.89-1.95), Lung disease (HR = 1.42; 95%
CI 1.40-1.44) and cerebrovascular disease (HR = 1.39; 95% CI 1.37-1.40). Among
psychiatric comorbidities, mortality risk was highest in those with substance
abuse (HR = 1.50; 95% CI 1.46-1.54), psychoses (HR = 1.16; 95% CI 1.14-1.19) and
depression (HR = 1.05; 95% CI 1.03-1.07). There was an interaction between
medical and psychiatric comorbidity (p = 0.003) so stratified analyses were
performed. HRs for effect of 3+ medical comorbidity (2.63, 2.66, 2.15) remained
high across levels of psychiatric comorbidities (0, 1, 2+), respectively. HRs for
effect of 2+ psychiatric comorbidity (1.69, 1.63, 1.42, 1.38) declined across
levels of medical comorbidity (0, 1, 2, 3+), respectively. CONCLUSIONS: Medical
and psychiatric multi-morbidity are significant predictors of mortality among
older adults (veterans) with type 2 diabetes with a graded response as
multimorbidity increases.
PMID- 25138209
TI - Waveband selection of reagent-free determination for thalassemia screening
indicators using Fourier transform infrared spectroscopy with attenuated total
reflection.
AB - A reagent-free determination method for the thalassemia screening indicators
hemoglobin (Hb), mean corpuscular Hb (MCH), and mean corpuscular volume (MCV) was
developed based on Fourier transform infrared spectrometers equipped with an
attenuated total reflection accessory. A random and stability-dependent rigorous
process of calibration, prediction, and validation was conducted. Appropriate
wavebands were selected using the improved moving window partial least squares
method with stability and equivalence. The obtained optimal wavebands were 1722
to 1504 cm-1 for Hb, 1653 to 901 cm-1 for MCH, and 1562 to 964 cm-1 for MCV. A
model set equivalent to the optimal model was proposed for each indicator; the
public waveband of Hb equivalent wavebands was 1717 to 1510 cm-1, and the public
equivalent waveband for MCH and MCV was 1562 to 901 cm-1. All selected wavebands
were within the MIR fingerprint region and achieved high validation effects. The
sensitivity and specificity were 100.0% and 96.9% for the optimal wavebands and
100.0% and 95.3% for the equivalent wavebands, respectively. Thus, the spectral
prediction was highly accurate for determining negative and positive for
thalassemia screening. This technique is rapid and simple in comparison with
conventional methods and is a promising tool for thalassemia screening in large
populations.
PMID- 25138204
TI - Immunotherapy using lipopolysaccharide-stimulated bone marrow-derived dendritic
cells to treat experimental autoimmune encephalomyelitis.
AB - Lipopolysaccharide (LPS) produced by Gram-negative bacteria induces tolerance and
suppresses inflammatory responses in vivo; however, the mechanisms are poorly
understood. In this study we show that LPS induces apoptosis of bone marrow
derived dendritic cells (DCs) and modulates phenotypes of DCs. LPS treatment up
regulates expression of tolerance-associated molecules such as CD205 and galectin
1, but down-regulates expression of Gr-1 and B220 on CD11c(+) DCs. Moreover, LPS
treatment regulates the numbers of CD11c(+) CD8(+) , CD11c(+) CD11b(low) and
CD11c(+) CD11b(hi) DCs, which perform different immune functions in vivo. Our
data also demonstrated that intravenous transfer of LPS-treated DCs blocks
experimental autoimmune encephalomyelitis (EAE) development and down-regulates
expression of retinoic acid-related orphan receptor gamma t (ROR-gammat),
interleukin (IL)-17A, IL-17F, IL-21, IL-22 and interferon (IFN)-gamma in myelin
oligodendrocyte glycoprotein (MOG)-primed CD4(+) T cells in the peripheral
environment. These results suggest that LPS-induced apoptotic DCs may lead to
generation of tolerogenic DCs and suppress the activity of MOG-stimulated
effector CD4(+) T cells, thus inhibiting the development of EAE in vivo. Our
results imply a potential mechanism of LPS-induced tolerance mediated by DCs and
the possible use of LPS-induced apoptotic DCs to treat autoimmune diseases such
as multiple sclerosis.
PMID- 25138210
TI - Idiopathic normal pressure hydrocephalus: cerebral perfusion measured with pCASL
before and repeatedly after CSF removal.
AB - Pseudo-continuous arterial spin labeling (pCASL) measurements were performed in
20 patients with idiopathic normal pressure hydrocephalus (iNPH) to investigate
whether cerebral blood flow (CBF) increases during the first 24 hours after a
cerebrospinal fluid tap test (CSF TT). Five pCASL magnetic resonance imaging
(MRI) scans were performed. Two scans were performed before removal of 40 mL CSF,
and the other three at 30 minutes, 4 hours, and 24 hours, respectively after the
CSF TT. Thirteen different regions of interest (ROIs) were manually drawn on
coregistered MR images. In patients with increased CBF in lateral and frontal
white matter after the CSF TT, gait function improved more than it did in
patients with decreased CBF in these regions. However, in the whole sample, there
was no significant increase in CBF after CSF removal compared with baseline
investigations. The repeatability of CBF measurements at baseline was high, with
intraclass correlation coefficients of 0.60 to 0.90 for different ROIs, but the
median regional variability was in the range of 5% to 17%. Our results indicate
that CBF in white matter close to the lateral ventricles plays a role in the
reversibility of symptoms after CSF removal in patients with iNPH.
PMID- 25138212
TI - Oncologic validity of recipient vessel preservation in microvascular free-flap
reconstruction.
AB - OBJECTIVES: The use of free-flap reconstruction requires a more limited neck
dissection to allow for microvascular anastomosis. This study seeks to determine
the oncologic validity of cervical vessel preservation. MATERIALS AND METHODS:
The current study is a prospective review of cervical vessel biopsies from
patients undergoing resection of squamous cell carcinoma (SCCA) tumors of the
head and neck with free tissue reconstruction. RESULTS: From June 2010 to March
2012, 227 recipient vessel biopsies were performed on 100 patients. Three of
these patients had grossly abnormal vessels, with malignancy confirmed by frozen
section analysis. One patient had a vessel positive for malignancy that was
grossly normal but found to have SCCA on the final pathology. CONCLUSIONS: When
the recipient vessel appears grossly suspicious, a frozen section biopsy and re
resection should be considered. Recipient vessel trimmings should routinely be
sent for permanent pathology since in rare cases, they can be involved by tumor,
affecting the margin status, prognosis, and indications for adjuvant therapy.
PMID- 25138213
TI - miR-326-histone deacetylase-3 feedback loop regulates the invasion and
tumorigenic and angiogenic response to anti-cancer drugs.
AB - Histone modification is known to be associated with multidrug resistance
phenotypes. Cancer cell lines that are resistant or have been made resistant to
anti-cancer drugs showed lower expression levels of histone deacetylase-3
(HDAC3), among the histone deacetylase(s), than cancer cell lines that were
sensitive to anti-cancer drugs. Celastrol and Taxol decreased the expression of
HDAC3 in cancer cell lines sensitive to anti-cancer drugs. HDAC3 negatively
regulated the invasion, migration, and anchorage-independent growth of cancer
cells. HDAC3 conferred sensitivity to anti-cancer drugs in vitro and in vivo.
TargetScan analysis predicted miR-326 as a negative regulator of HDAC3. ChIP
assays and luciferase assays showed a negative feedback loop between HDAC3 and
miR-326. miR-326 decreased the apoptotic effect of anti-cancer drugs, and the miR
326 inhibitor increased the apoptotic effect of anti-cancer drugs. miR-326
enhanced the invasion and migration potential of cancer cells. The miR-326
inhibitor negatively regulated the tumorigenic, metastatic, and angiogenic
potential of anti-cancer drug-resistant cancer cells. HDAC3 showed a positive
feedback loop with miRNAs such as miR-200b, miR-217, and miR-335. miR-200b, miR
217, and miR-335 negatively regulated the expression of miR-326 and the invasion
and migration potential of cancer cells while enhancing the apoptotic effect of
anti-cancer drugs. TargetScan analysis predicted miR-200b and miR-217 as negative
regulators of cancer-associated gene, a cancer/testis antigen, which is known to
regulate the response to anti-cancer drugs. HDAC3 and miR-326 acted upstream of
the cancer-associated gene. Thus, we show that the miR-326-HDAC3 feedback loop
can be employed as a target for the development of anti-cancer therapeutics.
PMID- 25138214
TI - Vesicle associated membrane protein 8 (VAMP8)-mediated zymogen granule exocytosis
is dependent on endosomal trafficking via the constitutive-like secretory
pathway.
AB - Acinar cell zymogen granules (ZG) express 2 isoforms of the vesicle-associated
membrane protein family (VAMP2 and -8) thought to regulate exocytosis. Expression
of tetanus toxin to cleave VAMP2 in VAMP8 knock-out (-/-) acini confirmed that
VAMP2 and -8 are the primary VAMPs for regulated exocytosis, each contributing
~50% of the response. Analysis of VAMP8(-/-) acini indicated that although
stimulated secretion was significantly reduced, a compensatory increase in
constitutive secretion maintained total secretion equivalent to wild type (WT).
Using a perifusion system to follow secretion over time revealed VAMP2 mediates
an early rapid phase peaking and falling within 2-3 min, whereas VAMP8 controls a
second prolonged phase that peaks at 4 min and slowly declines over 20 min to
support the protracted secretory response. VAMP8(-/-) acini show increased
expression of the endosomal proteins Ti-VAMP7 (2-fold) and Rab11a (4-fold) and
their redistribution from endosomes to ZGs. Expression of GDP-trapped Rab11a-S25N
inhibited secretion exclusively from the VAMP8 but not the VAMP2 pathway. VAMP8(
/-) acini also showed a >90% decrease in the early endosomal proteins
Rab5/D52/EEA1, which control anterograde trafficking in the constitutive-like
secretory pathway. In WT acini, short term (14-16 h) culture also results in a
>90% decrease in Rab5/D52/EEA1 and a complete loss of the VAMP8 pathway, whereas
VAMP2-secretion remains intact. Remarkably, rescue of Rab5/D52/EEA1 expression
restored the VAMP8 pathway. Expressed D52 shows extensive colocalization with
Rab11a and VAMP8 and partially copurifies with ZG fractions. These results
indicate that robust trafficking within the constitutive-like secretory pathway
is required for VAMP8- but not VAMP2-mediated ZG exocytosis.
PMID- 25138215
TI - Transcriptional regulation of the intestinal nuclear bile acid farnesoid X
receptor (FXR) by the caudal-related homeobox 2 (CDX2).
AB - Farnesoid X receptor (FXR, NR1H4) is a bile acid-activated transcription factor
that belongs to the nuclear receptor superfamily. It is highly expressed in the
enterohepatic system, where it senses bile acid levels to consequently reduce
their synthesis while inducing their detoxification. Bile acids are intestinal
tumor promoters and their concentrations have to be tightly regulated. Indeed,
reduced expression of FXR in the intestine increases colorectal cancer
susceptibility in mice, whereas its activation can promote apoptosis in
genetically modified cells. Notably, despite the broad knowledge of the FXR
enterohepatic transcriptional activity, the molecular mechanisms regulating FXR
expression in the intestine are still unknown. Herein, by combining both gain and
loss of function approaches and FXR promoter activity studies, we identified
caudal-related homeobox 2 (CDX2) transcription factor as a positive regulator of
FXR expression in the enterocytes. Our results provide a putative novel tool for
modulating FXR expression against bile acid-related colorectal cancer
progression.
PMID- 25138211
TI - Targeting TRP channels for novel migraine therapeutics.
AB - Migraine is increasingly understood to be a disorder of the brain. In susceptible
individuals, a variety of "triggers" may influence altered central excitability,
resulting in the activation and sensitization of trigeminal nociceptive afferents
surrounding blood vessels (i.e., the trigeminovascular system), leading to
migraine pain. Transient receptor potential (TRP) channels are expressed in a
subset of dural afferents, including those containing calcitonin gene related
peptide (CGRP). Activation of TRP channels promotes excitation of nociceptive
afferent fibers and potentially lead to pain. In addition to pain, allodynia to
mechanical and cold stimuli can result from sensitization of both peripheral
afferents and of central pain pathways. TRP channels respond to a variety of
endogenous conditions including chemical mediators and low pH. These channels can
be activated by exogenous stimuli including a wide range of chemical and
environmental irritants, some of which have been demonstrated to trigger migraine
in humans. Activation of TRP channels can elicit CGRP release, and blocking the
effects of CGRP through receptor antagonism or antibody strategies has been
demonstrated to be effective in the treatment of migraine. Identification of
approaches that can prevent activation of TRP channels provides an additional
novel strategy for discovery of migraine therapeutics.
PMID- 25138216
TI - Regression of replication forks stalled by leading-strand template damage: I.
Both RecG and RuvAB catalyze regression, but RuvC cleaves the holliday junctions
formed by RecG preferentially.
AB - The orderly progression of replication forks formed at the origin of replication
in Escherichia coli is challenged by encounters with template damage, slow moving
RNA polymerases, and frozen DNA-protein complexes that stall the fork. These
stalled forks are foci for genomic instability and must be reactivated. Many
models of replication fork reactivation invoke nascent strand regression as an
intermediate in the processing of the stalled fork. We have investigated the
replication fork regression activity of RecG and RuvAB, two proteins commonly
thought to be involved in the process, using a reconstituted DNA replication
system where the replisome is stalled by collision with leading-strand template
damage. We find that both RecG and RuvAB can regress the stalled fork in the
presence of the replisome and SSB; however, RuvAB generates a completely unwound
product consisting of the paired nascent leading and lagging strands, whereas
RuvC cleaves the Holliday junction generated by RecG-catalyzed fork regression.
We also find that RecG stimulates RuvAB-catalyzed regression, presumably because
it is more efficient at generating the initial Holliday junction from the stalled
fork.
PMID- 25138217
TI - Regression of replication forks stalled by leading-strand template damage: II.
Regression by RecA is inhibited by SSB.
AB - Stalled replication forks are sites of chromosome breakage and the formation of
toxic recombination intermediates that undermine genomic stability. Thus,
replication fork repair and reactivation are essential processes. Among the many
models of replication fork reactivation is one that invokes fork regression
catalyzed by the strand exchange protein RecA as an intermediate in the
processing of the stalled fork. We have investigated the replication fork
regression activity of RecA using a reconstituted DNA replication system where
the replisome is stalled by collision with leading-strand template damage. We
find that RecA is unable to regress the stalled fork in the presence of the
replisome and SSB. If the replication proteins are removed from the stalled fork,
RecA will catalyze net regression as long as the Okazaki fragments are sealed.
RecA-generated Holliday junctions can be detected by RuvC cleavage, although this
is not a robust reaction. On the other hand, extensive branch migration by RecA,
where a completely unwound product consisting of the paired nascent leading and
lagging strands is produced, is observed under conditions where RuvC activity is
suppressed. This branch migration reaction is inhibited by SSB, possibly
accounting for the failure of RecA to generate products in the presence of the
replication proteins. Interestingly, we find that the RecA-RuvC reaction is
supported to differing extents, depending on the template damage; templates
carrying a cyclopyrimidine dimer elicit more RecA-RuvC product than those
carrying a synthetic abasic site. This difference could be ascribed to a higher
affinity of RecA binding to DNAs carrying a thymidine dimer than to those with an
abasic site.
PMID- 25138218
TI - Formation of amyloid fibers by monomeric light chain variable domains.
AB - Systemic light chain amyloidosis is a lethal disease characterized by excess
immunoglobulin light chains and light chain fragments composed of variable
domains, which aggregate into amyloid fibers. These fibers accumulate and damage
organs. Some light chains induce formation of amyloid fibers, whereas others do
not, making it unclear what distinguishes amyloid formers from non-formers. One
mechanism by which sequence variation may reduce propensity to form amyloid
fibers is by shifting the equilibrium toward an amyloid-resistant quaternary
structure. Here we identify the monomeric form of the Mcg immunoglobulin light
chain variable domain as the quaternary unit required for amyloid fiber assembly.
Dimers of Mcg variable domains remain stable and soluble, yet become prone to
assemble into amyloid fibers upon disassociation into monomers.
PMID- 25138219
TI - Nod-like receptor protein 3 (NLRP3) inflammasome activation and podocyte injury
via thioredoxin-interacting protein (TXNIP) during hyperhomocysteinemia.
AB - NADPH oxidase-derived reactive oxygen species (ROS) have been reported to
activate NLRP3 inflammasomes resulting in podocyte and glomerular injury during
hyperhomocysteinemia (hHcys). However, the mechanism by which the inflammasome
senses ROS is still unknown in podocytes upon hHcys stimulation. The current
study explored whether thioredoxin-interacting protein (TXNIP), an endogenous
inhibitor of the antioxidant thioredoxin and ROS sensor, mediates hHcys-induced
NLRP3 inflammasome activation and consequent glomerular injury. In cultured
podocytes, size exclusion chromatography and confocal microscopy showed that
inhibition of TXNIP by siRNA or verapamil prevented Hcys-induced TXNIP protein
recruitment to form NLRP3 inflammasomes and abolished Hcys-induced increases in
caspase-1 activity and IL-1beta production. TXNIP inhibition protected podocytes
from injury as shown by normal expression levels of podocyte markers, podocin and
desmin. In vivo, adult C57BL/6J male mice were fed a folate-free diet for 4 weeks
to induce hHcys, and TXNIP was inhibited by verapamil (1 mg/ml in drinking water)
or by local microbubble-ultrasound TXNIP shRNA transfection. Evidenced by
immunofluorescence and co-immunoprecipitation studies, glomerular inflammasome
formation and TXNIP binding to NLRP3 were markedly increased in mice with hHcys
but not in TXNIP shRNA-transfected mice or those receiving verapamil.
Furthermore, TXNIP inhibition significantly reduced caspase-1 activity and IL
1beta production in glomeruli of mice with hHcys. Correspondingly, TXNIP shRNA
transfection and verapamil attenuated hHcys-induced proteinuria, albuminuria,
glomerular damage, and podocyte injury. In conclusion, our results demonstrate
that TXNIP binding to NLRP3 is a key signaling mechanism necessary for hHcys
induced NLRP3 inflammasome formation and activation and subsequent glomerular
injury.
PMID- 25138222
TI - Sustained remission of blastic plasmacytoid dendritic cell neoplasm after
unrelated allogeneic stem cell transplantation--a single center experience.
AB - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematodermic
neoplasm which typically presents with skin infiltrates with or without
lymphadenopathy and bone marrow involvement. No standard of care exists for this
aggressive disease and prognosis is particularly poor. Here, we present our
experience with nine BPDCN patients diagnosed at our institution between 2005 and
2012. BPDCN patients were identified in the databases at the Department of
Hematology and Oncology, the Department of Dermatology, and the Institute of
Pathology at the Otto-von-Guericke-University Magdeburg. There were six male and
three female patients with a median age at diagnosis of 66 years. Sites involved
were skin (five cases), lymph nodes (five cases), and bone marrow (five cases).
Treatments varied from single agent chemotherapy to polychemotherapy and
allogeneic stem cell transplantation for consolidation. The three patients that
were treated with acute leukemia-type induction therapy followed by allogeneic
stem cell transplantation (one after standard conditioning and two after reduced
intensity conditioning using fludarabine in combination with thiotepa) achieved
sustained remissions and are alive with a follow-up of 8, 35, and 41 months. In
contrast, median survival in the less intensively treated patients was only 9.5
(range 1 to 29) months.
PMID- 25138221
TI - Roles of Bacillus subtilis DprA and SsbA in RecA-mediated genetic recombination.
AB - Bacillus subtilis competence-induced RecA, SsbA, SsbB, and DprA are required to
internalize and to recombine single-stranded (ss) DNA with homologous resident
duplex. RecA, in the ATP . Mg(2+)-bound form (RecA . ATP), can nucleate and form
filament onto ssDNA but is inactive to catalyze DNA recombination. We report that
SsbA or SsbB bound to ssDNA blocks the RecA filament formation and fails to
activate recombination. DprA facilitates RecA filamentation; however, the
filaments cannot engage in DNA recombination. When ssDNA was preincubated with
SsbA, but not SsbB, DprA was able to activate DNA strand exchange dependent on
RecA . ATP. This work demonstrates that RecA . ATP, in concert with SsbA and
DprA, catalyzes DNA strand exchange, and SsbB is an accessory factor in the
reaction. In contrast, RecA . dATP efficiently catalyzes strand exchange even in
the absence of single-stranded binding proteins or DprA, and addition of the
accessory factors marginally improved it. We proposed that the RecA-bound
nucleotide (ATP and to a lesser extent dATP) might dictate the requirement for
accessory factors.
PMID- 25138220
TI - Rapid binding of plasminogen to streptokinase in a catalytic complex reveals a
three-step mechanism.
AB - Rapid kinetics demonstrate a three-step pathway of streptokinase (SK) binding to
plasminogen (Pg), the zymogen of plasmin (Pm). Formation of a fluorescently
silent encounter complex is followed by two conformational tightening steps
reported by fluorescence quenches. Forward reactions were defined by time courses
of biphasic quenching during complex formation between SK or its COOH-terminal
Lys(414) deletion mutant (SKDeltaK414) and active site-labeled [Lys]Pg ([5
(acetamido)fluorescein]-D-Phe-Phe-Arg-[Lys]Pg ([5F]FFR-[Lys]Pg)) and by the SK
dependences of the quench rates. Active site-blocked Pm rapidly displaced [5F]FFR
[Lys]Pg from the complex. The encounter and final SK .[5F]FFR-[Lys]Pg complexes
were weakened similarly by SK Lys(414) deletion and blocking of lysine-binding
sites (LBSs) on Pg kringles with 6-aminohexanoic acid or benzamidine. Forward and
reverse rates for both tightening steps were unaffected by 6-aminohexanoic acid,
whereas benzamidine released constraints on the first conformational tightening.
This indicated that binding of SK Lys(414) to Pg kringle 4 plays a role in
recognition of Pg by SK. The substantially lower affinity of the final SK . Pg
complex compared with SK . Pm is characterized by a ~ 25-fold weaker encounter
complex and ~ 40-fold faster off-rates for the second conformational step. The
results suggest that effective Pg encounter requires SK Lys(414) engagement and
significant non-LBS interactions with the protease domain, whereas Pm binding
additionally requires contributions of other lysines. This difference may be
responsible for the lower affinity of the SK . Pg complex and the expression of a
weaker "pro"-exosite for binding of a second Pg in the substrate mode compared
with SK . Pm.
PMID- 25138223
TI - Good lateral harmonic stability combined with adequate gait speed is required for
low fall risk in older people.
AB - BACKGROUND: Good lateral harmonic stability in gait may be important for
minimising fall risk in older people because many falls occur during walking when
the base of support is narrowest in the mediolateral (ML) direction. However, the
traditional ML harmonic ratio (MLHR) may be a sub-optimal measure of gait quality
because of insufficient frequency resolution. OBJECTIVE: The primary objective
was to investigate if a new measure of lateral harmonic stability, the 8-step
MLHR, could discriminate older fallers from non-fallers while taking different
walking speeds into account. METHODS: Repeat walks over 20 m were completed by 96
older people (mean age 80, SD 4 years); 35 participants had a history of one or
more falls in the past year. The traditional MLHR and the 8-step MLHR were
obtained from an accelerometer attached to the sacrum. RESULTS: Compared to the
traditional MLHR, the 8-step MLHR demonstrated similar univariate ability to
identify significant differences in fall risk based on age, walking speed and
physiology (p <= 0.05). When differences in walking speed were taken into
account, we observed that participants who walked both faster than average and
had above-average lateral harmonic stability (by the 8-step MLHR) were 5.3 times
less likely to be fallers than all other participants (relative risk: 0.19, 95%
confidence interval: 0.06-0.57). For the traditional MLHR, however, no
significant differences between the fallers and non-fallers were evident.
CONCLUSIONS: The findings indicate that good lateral harmonic stability interacts
with adequate gait speed and, when coincident, are associated with reduced fall
risk in older people. Future research could examine whether interventions
focusing on enhancing both gait speed and lateral stability can reduce fall risk
and whether these combined gait measures can remotely predict deteriorating
health using wearable technology.
PMID- 25138224
TI - Efficacy and tolerability of fixed-combination brinzolamide/timolol in Latin
American patients with open-angle glaucoma or ocular hypertension previously on
brimonidine/timolol fixed combination.
AB - INTRODUCTION: Fixed-combination glaucoma medications are commonly used to achieve
target intraocular pressure (IOP) reduction in patients uncontrolled with
monotherapy; however, ocular discomfort associated with eye drops can decrease
adherence. This study assessed the efficacy and tolerability of twice-daily fixed
combination brinzolamide 1%/timolol 0.5% (BRINZ/TIM-FC) in Latin American
patients transitioned from fixed-combination brimonidine 0.2%/timolol 0.5%
(BRIM/TIM-FC) because of insufficient IOP control or treatment intolerance.
METHODS: This 8-week, open-label, prospective study was conducted at six sites in
Argentina, Chile, and Mexico. Enrolled patients were aged >=18 years with open
angle glaucoma (including primary, exfoliative, or pigment-dispersion glaucoma)
or ocular hypertension with IOP of 19-35 mmHg in >=1 eye at baseline (on BRIM/TIM
FC). Patients self-administered BRINZ/TIM-FC to both eyes at 8 a.m. and 8 p.m.
daily for 8 weeks. The primary and secondary efficacy endpoints were mean IOP
change from baseline at week 8 and percentage of patients achieving target IOP
(<=18 mmHg) at week 8, respectively. Exploratory endpoints included patient and
investigator preference for treatment at week 8. Adverse events (AEs) were
assessed as the safety endpoint. RESULTS: Fifty patients (mean +/- SD age, 66.7
+/- 11.5 years) received BRINZ/TIM-FC, and 49 were included in the intent-to
treat population. Mean +/- SD IOP was significantly reduced from baseline after 8
weeks of treatment with BRINZ/TIM-FC (-3.6 +/- 3.0 mmHg; P < 0.0001, Wilcoxon
signed-rank test; 17.1% reduction). Overall, 55.3% of patients achieved IOP <=18
mmHg at week 8. Significantly more patients (89.4%) and investigators (95.7%)
preferred BRINZ/TIM-FC to BRIM/TIM-FC (both P < 0.0001, exact binomial test). Of
the 13 AEs observed, 8 were related to BRINZ/TIM-FC; the most common treatment
related AEs were eye irritation (n = 4) and abnormal sensation in the eye (n =
2). CONCLUSION: BRINZ/TIM-FC provides an effective and well-tolerated treatment
option for patients transitioned from BRIM/TIM-FC.
PMID- 25138225
TI - Syphilis Infection: An Uncommon Etiology of Infectious Nonimmune Fetal Hydrops
with Anemia.
AB - An increased prevalence of syphilis has been observed in many developed countries
over the last decade. During pregnancy, syphilis can affect the fetus through
development of nonspecific symptoms such as microcephaly, ascites,
hepatosplenomegaly, dilated and echogenic bowel, placentomegaly, and, uncommonly,
fetal hydrops. Congenital syphilis also leads to hematologic abnormalities such
as anemia, thrombocytopenia, leukopenia, and leukocytosis. We present a case of
nonimmune fetal hydrops with anemia related to syphilis infection. Diagnosis was
confirmed by a maternal serological test and microbiological testing on amniotic
fluid, umbilical cord, and placental tissues. The patient was treated with
penicillin and the fetus received an intrauterine red blood cell transfusion, but
fetal death occurred shortly after. Such a presentation is mostly related to
parvovirus B19, and syphilis etiology is poorly mentioned because physicians have
rarely seen early congenital syphilis in the past. However, given the increasing
prevalence of this disease in the adult population, clinicians should remain
alert to the various presentations of congenital syphilis.
PMID- 25138227
TI - Secretoneurin as a marker for hypoxic brain injury after cardiopulmonary
resuscitation.
AB - PURPOSE: The neuropeptide secretoneurin (SN) shows widespread distribution in the
brain. We evaluated whether SN is elevated after cardiopulmonary resuscitation
(CPR) and could serve as a potential new biomarker for hypoxic brain injury after
CPR. METHODS: This was a prospective observational clinical study. All patients
admitted to a tertiary medical intensive care unit after successful CPR with
expected survival of at least 24 h were consecutively enrolled from September
2008 to April 2013. Serum SN and neuron-specific enolase were determined in 24 h
intervals starting with the day of CPR for 7 days. Neurological outcome was
assessed with the Cerebral Performance Categories Scale (CPC) at hospital
discharge. RESULTS: A total of 134 patients were included with 49 % surviving to
good neurological outcome (CPC 1-2). SN serum levels peaked within the first 24 h
showing on average a sixfold increase above normal. SN levels were significantly
higher in patients with poor (CPC 3-5) than in patients with good neurological
outcome [0-24 h: 75 (43-111) vs. 38 (23-68) fmol/ml, p < 0.001; 24-48 h: 45 (24
77) vs. 23 (16-39) fmol/ml, p < 0.001]. SN determined within the first 48 h
showed a receiver operating characteristic (ROC) area under the curve (AUC) of
0.753 (0.665-0.841). NSE in the first 72 h had a ROC-AUC of 0.881 (0.815-0.946).
When combining the two biomarkers an AUC of 0.925 (0.878-0.972) for outcome
prediction could be reached. CONCLUSIONS: SN is a promising early biomarker for
hypoxic brain injury. Further studies will be required for confirmation of these
results.
PMID- 25138228
TI - Understanding incretins.
PMID- 25138230
TI - Ask the wrong question, you'll the get the wrong answer.
PMID- 25138229
TI - PROF-ETEV study: prophylaxis of venous thromboembolic disease in critical care
units in Spain.
AB - PURPOSE: Venous thromboembolic disease (VTE) in critically ill patients has a
high incidence despite prophylactic measures. This fact could be related to an
inappropriate use of these measures due to the absence of specific VTE risk
scores. To assess the current situation in Spain, we have performed a cross
sectional study, analyzing if the prophylactic measures were appropriate to the
patients' VTE risk. METHODS: Through an electronic questionnaire, we carried out
a single day point prevalence study on the VTE prophylactic measures used in
several critical care units in Spain. We performed a risk stratification for VTE
in three groups: low, moderate-high, and very high risk. The American College of
Chest Physicians guidelines were used to determine if the patients were receiving
the recommended prophylaxis. RESULTS: A total of 777 patients were included; 62%
medical, 30% surgical, and 7% major trauma patients. The median number of the
risk factors for VTE was four. According to the proposed VTE risk score, only 2%
of the patients were at low risk, whereas 83% were at very high risk. Sixty-three
percent of patients received pharmacological prophylaxis, 12% mechanical
prophylaxis, 6% combined prophylaxis, and 19% did not receive any prophylactic
measure. According to criteria suggested by the guidelines, 23% of medical, 71%
of surgical, and 70% of major trauma patients received an inappropriate
prophylaxis. CONCLUSIONS: Most critically ill patients are at high or very high
risk of VTE, but there is a low rate of appropriate prophylaxis. The efforts to
improve the identification of patients at risk, and the implementation of
appropriate prevention protocols should be enhanced.
PMID- 25138226
TI - Consensus summary statement of the International Multidisciplinary Consensus
Conference on Multimodality Monitoring in Neurocritical Care : a statement for
healthcare professionals from the Neurocritical Care Society and the European
Society of Intensive Care Medicine.
AB - Neurocritical care depends, in part, on careful patient monitoring but as yet
there are little data on what processes are the most important to monitor, how
these should be monitored, and whether monitoring these processes is cost
effective and impacts outcome. At the same time, bioinformatics is a rapidly
emerging field in critical care but as yet there is little agreement or
standardization on what information is important and how it should be displayed
and analyzed. The Neurocritical Care Society in collaboration with the European
Society of Intensive Care Medicine, the Society for Critical Care Medicine, and
the Latin America Brain Injury Consortium organized an international,
multidisciplinary consensus conference to begin to address these needs.
International experts from neurosurgery, neurocritical care, neurology, critical
care, neuroanesthesiology, nursing, pharmacy, and informatics were recruited on
the basis of their research, publication record, and expertise. They undertook a
systematic literature review to develop recommendations about specific topics on
physiologic processes important to the care of patients with disorders that
require neurocritical care. This review does not make recommendations about
treatment, imaging, and intraoperative monitoring. A multidisciplinary jury,
selected for their expertise in clinical investigation and development of
practice guidelines, guided this process. The GRADE system was used to develop
recommendations based on literature review, discussion, integrating the
literature with the participants' collective experience, and critical review by
an impartial jury. Emphasis was placed on the principle that recommendations
should be based on both data quality and on trade-offs and translation into
clinical practice. Strong consideration was given to providing pragmatic guidance
and recommendations for bedside neuromonitoring, even in the absence of high
quality data.
PMID- 25138231
TI - Ten years' experience for hypospadias repair: combined buccal mucosa graft and
local flap for urethral reconstruction.
AB - OBJECTIVES: To share our experience in hypospadias repair and discuss the
clinical implications of our method, which consists of a combined buccal mucosa
graft and local flap for urethroplasty. PATIENTS AND METHODS: 1,394 cases (median
age 11.3 years, age range 5 months to 53 years) of hypospadias which were
repaired using our method between July 2000 and December 2010 in our department
were included in this study. The patients who had a short penis or did not have
chordee were excluded from the data. 588 cases (42.2%) had previously undergone
surgery in other hospitals but failed; 806 (57.8%) cases had undergone the first
treatment in our department. RESULTS: Of the 806 cases which had undergone the
first treatment in our department, we successfully reconstructed the urethra for
747 patients (92.3%), and 59 patients had complications (7.7%); of the 588 cases
which had previously undergone surgery but failed, we successfully reconstructed
the urethra for 522 patients (88.8%), and 66 patients had complications (11.2%).
The most common complication was urethra fistula (70; 5%); other complications
include necrosis of the skin flap and infection resulting in wound disruption
(19; 1.4%), urethral diverticula (11; 0.8%) and urethral stricture (25; 1.8%).
CONCLUSIONS: Our method appears to be a safe, simple and satisfactory surgical
procedure and can provide relatively enough tissue to reconstruct the urethra
with a higher success rate.
PMID- 25138232
TI - Caudal lumbar vertebral fractures in California Quarter Horse and Thoroughbred
racehorses.
AB - REASONS FOR PERFORMING STUDY: To gain insight into the pathophysiology of equine
lumbar vertebral fractures in racehorses. OBJECTIVES: To characterise equine
lumbar vertebral fractures in California racehorses. STUDY DESIGN: Retrospective
case series and prospective case-control study. METHODS: Racehorse post mortem
reports and jockey injury reports were retrospectively reviewed. Vertebral
specimens from 6 racehorses affected with lumbar vertebral fractures and 4
control racehorses subjected to euthanasia for nonspinal fracture were assessed
using visual, radiographic, computed tomography and histological examinations.
RESULTS: Lumbar vertebral fractures occurred in 38 Quarter Horse and 29
Thoroughbred racehorses over a 22 year period, primarily involving the 5th and/or
6th lumbar vertebrae (L5-L6; 87% of Quarter Horses and 48% of Thoroughbreds).
Lumbar vertebral fractures were the third most common musculoskeletal cause of
death in Quarter Horses and frequently involved a jockey injury. Lumbar vertebral
specimens contained anatomical variations in the number of vertebrae, dorsal
spinous processes and intertransverse articulations. Lumbar vertebral fractures
examined in 6 racehorse specimens (5 Quarter Horses and one Thoroughbred) coursed
obliquely in a cranioventral to caudodorsal direction across the adjacent L5-L6
vertebral endplates and intervertebral disc, although one case involved only one
endplate. All cases had evidence of abnormalities on the ventral aspect of the
vertebral bodies consistent with pre-existing, maladaptive pathology.
CONCLUSIONS: Lumbar vertebral fractures occur in racehorses with pre-existing
pathology at the L5-L6 vertebral junction that is likely predisposes horses to
catastrophic fracture. Knowledge of these findings should encourage assessment of
the lumbar vertebrae, therefore increasing detection of mild vertebral injuries
and preventing catastrophic racehorse and associated jockey injuries.
PMID- 25138233
TI - Unwanted childbearing and household food insecurity in the United States.
AB - Household food insecurity is a population health concern disproportionately
affecting families with children in the United States. Unwanted childbearing may
place unanticipated strain on families to meet basic needs, heightening the risk
for household food insecurity. We investigated the association between mother's
and father's report of unwanted childbearing and exposure to household food
insecurity among children residing in two-parent households in the United States.
Data from the Early Childhood Longitudinal Study - Birth Cohort, a nationally
representative cohort of US children (n ~ 6150), were used to estimate the odds
of household food insecurity when children were aged 9 months and 2 years,
separately, based on parental report of unwanted childbearing. The majority of
children were reported as wanted by both parents (74.4%). Of the sample, report
of unwanted childbearing by father-only was 20.0%, mother-only was 3.4% and joint
mother and father was 2.2%. Household food insecurity was higher when children
were 9 months compared with 2 years. In adjusted models accounting for
confounders, children born to mothers and fathers who jointly reported unwanted
childbearing were at higher odds of exposure to household food insecurity at 9
months [adjusted odds ratio (AOR) = 3.31; 95% confidence interval (CI): 1.97,
5.57] and 2 years (AOR = 2.52; 95% CI: 1.12, 5.68). In two-parent households, we
found that children raised by parents reporting unwanted childbearing were more
likely to be exposed to food insecurity and potentially related stressors.
Further studies that prospectively measure wantedness before the child's birth
will aid in confirming the direction of this association.
PMID- 25138235
TI - Current research and recent breakthroughs on the mental health effects of
disasters.
AB - A large existing academic disaster mental health literature provides a foundation
to help guide disaster mental health response. Recent studies, however, have
indicated that reconceptualization of certain mental health aspects of disasters
may be indicated to guide further research to inform the planning and
implementation of disaster mental health interventions. In particular, there is
need to more carefully measure specific postdisaster disorders and syndromes
using full diagnostic assessments, differentiate pre-existing from incident (new)
postdisaster psychopathology, appropriately consider disaster trauma exposure
groups in assessing psychopathology, and conduct prospective follow-up
assessments over time from the acute postdisaster period to the long term.
Further descriptive and longitudinal research is needed to better characterize
the occurrence and course of fully-assessed psychiatric disorders after different
disasters, clarify the role of disaster trauma exposures in the development of
postdisaster psychopathology, and deconstruct confounding effects in
determination of causalities in mental health consequences of disasters.
PMID- 25138234
TI - Antipsychotic induced weight gain: genetics, epigenetics, and biomarkers
reviewed.
AB - Antipsychotic-induced weight gain (AIWG) is a prevalent side effect of
antipsychotic treatment, particularly with second generation antipsychotics, such
as clozapine and olanzapine. At this point, there is virtually nothing that can
be done to predict who will be affected by AIWG. However, hope for the future of
prediction lies with genetic risk factors. Many genes have been studied for their
association with AIWG with a variety of promising findings. This review will
focus on genetic findings in the last year and will discuss the first epigenetic
and biomarker findings as well. Although there are significant findings in many
other genes, the most consistently replicated findings are in the melanocortin 4
receptor (MC4R), the serotonin 2C receptor (HTR2C), the leptin, the neuropeptide
Y (NPY) and the cannabinoid receptor 1 (CNR1) genes. The study of genetic risk
variants poses great promise in creating predictive tools for side effects such
as AIWG.
PMID- 25138237
TI - Variation in seminal plasma alters the ability of ram spermatozoa to survive
cryopreservation.
AB - Variation in the effect of seminal plasma on sperm function and fertility has
been hypothesised to be due to differences between males and their seminal plasma
composition. The freezing resilience of individual rams (n=17) was investigated
to characterise inter-male variation. This was determined by measuring the degree
of change in motility induced by cryopreservation (Experiment 1). Experiment 2
examined the effect of pooled seminal plasma from rams identified as having high
or low resilience to freezing on the cryosurvival of washed spermatozoa from
either high (n=3) or low (n=3) sperm freezing resilience rams. Immediately after
thawing and throughout the incubation period (0-4h), spermatozoa from high
resilience rams frozen with high-resilience seminal plasma demonstrated superior
motility to spermatozoa from high-resilience rams frozen with low-resilience
seminal plasma (P<0.001). Similarly, spermatozoa from low-resilience rams frozen
with high-resilience seminal plasma exhibited higher motility than spermatozoa
from low-resilience rams frozen with low-resilience seminal plasma immediately
after thawing (0h; P<0.001). The present study shows that variation in freezing
resilience of ram spermatozoa is related to the source and composition of the
seminal plasma.
PMID- 25138236
TI - Pharmacotherapy of anxiety disorders in German-speaking countries: current status
and changes between 1994 and 2011.
AB - Over the past years, international treatment guidelines have been established for
the treatment of anxiety disorders. Nevertheless, little is known as to whether
the actual inpatient treatment follows these guidelines. The main goal of this
study was to answer the question whether patients with anxiety disorder are
treated according to treatment guidelines. A total of 2,573 psychiatric
inpatients with the diagnosis of anxiety disorder (920 men, 1,653 women) were
identified on the basis of the data of the international drug safety programme in
psychiatry AMSP. Of these patients, 25.3% presented with phobia, 26.6% with panic
disorder, 18.7% with generalized anxiety disorder (GAD), and 29.4% with other
diagnoses of anxiety. In all of the patients, 12.7% did not receive any
psychotropic medication and 22.9% were not treated with antidepressants. Only
59.3% of patients with GAD, 73.9% of patients with panic disorder, and 52.1% of
patients with phobia were treated according to diagnostic guidelines. The
majority (60.3%) of all patients received one or two psychotropic drugs, and only
3.7% received five or more psychotropic drugs. In two groups of patients (one
group with phobia and one with panic disorder), the annual prescription rate of
antidepressants significantly increased over time. The prescription rate for
anticonvulsants in patients with GAD increased from 0% in 1997 to 41.7% in 2011,
and for antipsychotics, from 40.7% in 1997 to 47.2% in 2011. In particular,
patients with GAD were commonly treated with antipsychotics.
PMID- 25138238
TI - PIXSIC, a pixelated beta+-sensitive probe for radiopharmacological investigations
in rat brain: binding studies with [18F]MPPF.
AB - PURPOSE: The aim of this work was to demonstrate the pharmacokinetic potential of
a wireless pixelated beta(+)-sensitive probe (PIXSIC). PROCEDURES: The binding of
2'-methoxyphenyl-(N-2'-pyridinyl)-p-[(18)F]fluoro-benzamidoethylpiperazine
([(18)F]MPPF), a 5-HT1A serotonin receptor radiopharmaceutical, was measured in
anesthetized rats and compared to microPET data. The effects of a 5-HT1A
antagonist injection on in vivo [(18)F]MPPF binding were monitored by PIXSIC.
RESULTS: PIXSIC allowed differentiating the radioactive kinetics according to the
location of its pixels in the hippocampus, cortex, corpus callosum, and
cerebellum. The device accurately detected the changes in [(18)F]MPPF binding,
after 5-HT1A antagonist blockade. The time-activity curves were reproducible and
consistent with kinetics obtained simultaneously with a microPET camera.
CONCLUSIONS: These results demonstrate the ability of the PIXSIC device to record
reliably the binding of PET ligands, with a high spatiotemporal resolution in
anesthetized rodents. These first in vivo results are a key stage on the path to
its implementation in awake freely moving animals.
PMID- 25138240
TI - Dislocation mechanism of deuterium retention in tungsten under plasma
implantation.
AB - We have developed a new theoretical model for deuterium (D) retention in tungsten
based alloys on the basis of its being trapped at dislocations and transported to
the surface via the dislocation network with parameters determined by ab initio
calculations. The model is used to explain experimentally observed trends of D
retention under sub-threshold implantation, which does not produce stable lattice
defects to act as traps for D in conventional models. Saturation of D retention
with implantation dose and effects due to alloying of tungsten with, e.g.
tantalum, are evaluated, and comparison of the model predictions with
experimental observations under high-flux plasma implantation conditions is
presented.
PMID- 25138239
TI - Hypomagnesaemia associated with long-term use of proton pump inhibitors.
AB - Hypomagnesaemia and associated hypocalcaemia and hypoparathyroidism have been
increasingly recognised as rare long-term side-effects of proton pump inhibitors
(PPIs). The PPIs may inhibit active magnesium (Mg) absorption by interfering with
transcellular transient receptor potential melastatin-6 and -7 (TRPM 6 and 7)
channels. More recent cell culture studies have suggested concomitant inhibition
of passive Mg absorption by omeprazole. After being treated with a range of PPIs,
the four patients in our case series developed hypomagnesaemia, which responded
to withdrawal of therapy and initiation of Mg replacement. Their clinical course
and management demonstrate key aspects of hypomagnesaemia associated with long
term use of PPIs.
PMID- 25138241
TI - Analysis of the Italian generic medicines retail market: recommendations to
enhance long-term sustainability.
AB - Italy is among the European countries with the lowest uptake of generic
medicines. This paper provides a perspective on the Italian generic medicines
retail market. Fast market entrance of generic medicines in Italy is hindered by
several factors: the existence of Complementary Protection Certificates in the
past, the large market for copies and multiple cases of patent linkage. Prices of
generic medicines in Italy are low compared to other European countries. To
contain pharmaceutical expenditure, pharmaceutical companies are currently forced
to pay back in case of overspending, which disproportionally penalizes small and
fast growing companies, to which most generic companies belong to. Current demand
side policies do not successfully stimulate the use of generic medicines. The
current market environment surrounding the Italian generic medicines retail
market (i.e., low prices, low volumes) threatens its long-term sustainability.
Recommendations to enhance the long-term sustainability of the Italian generic
medicines retail market round off this perspective paper.
PMID- 25138243
TI - Central versus peripheral arterial cannulation and neurological outcomes after
thoracic aortic surgery: meta-analysis and meta-regression of 4459 patients.
AB - BACKGROUND: Thoracic aortic surgeries remain with high mortality rates, often
associated with postoperative neurological complications. The choice of the right
cannulation site is extremely important for suitable blood supply and maintenance
of vital functions, especially of the central nervous system. OBJECTIVES: To
compare the influence of central versus peripheral arterial cannulation on
neurological outcomes in patients undergoing thoracic aortic surgery through
systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, CENTRAL/CCTR,
SciELO, LILACS and reference lists of relevant articles were searched for
clinical studies that reported in-hospital neurological outcomes after central or
peripheral arterial cannulation during thoracic aortic surgery procedures until
December 2013. The principal summary measures were Odds Ratio (OR) for central
compared to peripheral arterial cannulation with 95% confidence interval (CI) and
p-values considered statistically significant when <0.05. The ORs were combined
across studies, using the DerSimonian-Laird random effects model and fixed
effects model using the Mantel-Haenszel model--both models were weighted. The
meta-analysis was completed using the software Comprehensive Meta-Analysis
version 2 (Biostat Inc., Englewood, NJ). RESULTS: Six studies were identified and
included a total of 4459 patients (1180 for central and 3279 for peripheral
cannulation). There was no significant difference between the central and
peripheral groups regarding neurological outcomes. The meta-regression evidenced
no relationship between neurological outcomes and the variables age, sex,
previous coronary event, previous neurological event, urgency surgery,
cardiopulmonary bypass time, activated clotting time and esophageal temperature
with p > 0,05. CONCLUSION: When it comes to neurological outcomes in patients
undergoing thoracic aortic surgery, there was no evidence that argues in favor of
any choice of arterial cannulation site, which makes us reject any superiority of
one approach over the other in this regard.
PMID- 25138242
TI - The regulatory effect of UL-16 binding protein-3 expression on the cytotoxicity
of NK cells in cancer patients.
AB - The activating immunoreceptor NKG2D (natural killer group 2, member D) and its
ligands play important roles in the innate and adaptive immune responses. UL16
binding protein 3 (ULBP3), an NKG2D ligand, is overexpressed on certain
epithelial tumor cells. In this study, we investigated the effect of ULBP3
expression on the cytotoxic activity of natural killer (NK) cells. ULBP3 were
measured by flow cytometry analysis, immunohistochemistry, and time-resolved
fluoroimmunoassay. The cytotoxicity of NK cells was determined with the lactate
dehydrogenase release assay. We found that ULBP3 was overexpressed on tumor cell
lines and tumor tissues. Serum from cancer patients, but not from healthy donors,
contained elevated levels of soluble ULBP3 (sULBP3). Importantly, high expression
of ULBP3 on the cell surface of tumor cells augmented NKG2D-mediated NK cell
cytotoxicity. However, low levels of sULBP3 (<15 ng/ml) weakened the cytotoxicity
of NK cells by decreasing NKG2D expression on NK cells. Further analysis showed
that serum samples from most cancer patients (>70%) contained the low level of
sULBP3. Our results demonstrate that tumor cells express surface and soluble
ULBP3, which regulate NK cell activity. Thus, ULBP3 is a potential therapeutic
target for improving the immune response against cancer.
PMID- 25138244
TI - Real-time data acquisition and alerts may reduce reaction time and improve
perfusionist performance during cardiopulmonary bypass.
AB - Delayed perfusionist identification and reaction to abnormal clinical situations
has been reported to contribute to increased mortality and morbidity. The use of
automated data acquisition and compliance safety alerts has been widely accepted
in many industries and its use may improve operator performance. A study was
conducted to evaluate the reaction time of perfusionists with and without the use
of compliance alert. A compliance alert is a computer-generated pop-up banner on
a pump-mounted computer screen to notify the user of clinical parameters outside
of a predetermined range. A proctor monitored and recorded the time from an alert
until the perfusionist recognized the parameter was outside the desired range.
Group one included 10 cases utilizing compliance alerts. Group 2 included 10
cases with the primary perfusionist blinded to the compliance alerts. In Group 1,
97 compliance alerts were identified and, in group two, 86 alerts were
identified. The average reaction time in the group using compliance alerts was
3.6 seconds. The average reaction time in the group not using the alerts was
nearly ten times longer than the group using computer-assisted, real-time data
feedback. Some believe that real-time computer data acquisition and feedback
improves perfusionist performance and may allow clinicians to identify and
rectify potentially dangerous situations.
PMID- 25138246
TI - Predictive factors for clinical response to allergy immunotherapy in children
with asthma and rhinitis.
AB - BACKGROUND: To date, no predictive methods for the clinical response to allergy
immunotherapy (AIT) are available. We sought to evaluate the pretreatment
parameters used in diagnosing allergic asthma and/or rhinitis including allergen
skin-prick test responses, serum specific and total IgE (sIgE and tIgE) levels
and blood eosinophil counts, and to identify whether these can be used to predict
clinical effectiveness in children treated with immunotherapy. METHODS: This
study involved 185 children who had undergone 3 years of standardized-quality
house-dust mite subcutaneous immunotherapy. Clinical characteristics and
laboratory parameters were analyzed. A multivariate unconditional logistic
regression model and receiver operating characteristic curves were used.
Predicted probabilities and predictive areas under the curve were calculated.
RESULTS: The clinical response to AIT was effective in 129/185 (69.7%) patients.
Four variables were associated with clinical response by multivariate logistic
analysis: tobacco smoke exposure [odds ratio (OR) 2.845 and 95% confidence
interval (CI) 1.147-7.058; p = 0.024], a family history of atopy (OR 2.881 and
95% CI 1.240-6.692; p = 0.014), a serum tIgE level >=965 kU/l (OR 5.917 and 95%
CI 2.320-15.089; p = 0.000) and an sIgE/tIgE ratio >=6% (OR 0.336 and 95% CI
0.124-0.911; p = 0.032). The sensitivity and specificity of the area under the
curve of the serum tIgE were higher than those of serum sIgE and sIgE/tIgE ratio
alone. CONCLUSION: Tobacco smoke exposure, atopic family history, serum tIgE and
sIgE/tIgE ratio were in significant correlation with clinical response to AIT in
children, which may be helpful for patient selection before immunotherapy. The
serum tIgE is superior to both the serum sIgE/tIgE ratio and sIgE levels alone in
predicting clinical effectiveness.
PMID- 25138248
TI - Negative Religious Coping Predicts Disordered Eating Pathology Among Orthodox
Jewish Adolescent Girls.
AB - Recent research suggests the importance of exploring religious and spiritual
factors in relation to the continuum of disordered eating. This continuum ranges
from mild disordered eating behaviors and attitudes to moderate levels of
disordered eating pathology (DEP) through full-blown clinical levels of eating
disorders (EDs). The current study is the first to explore the role that
religious coping (both positive and negative) plays in the development DEP, which
is considered a risk factor for the development of EDs. In addition, the study
aims to describe levels of DEP among a non-clinical sample of 102 Orthodox Jewish
adolescent females. Participants completed a questionnaire measuring religious
coping strategies, DEP and self-esteem. Results indicated that greater use of
negative religious coping was associated with higher levels of DEP. Mediation
analyses suggested that greater negative religious coping is related to lower
levels of self-esteem, which accounts for higher levels of DEP. Furthermore,
findings revealed relatively lower overall levels of DEP among this sample,
compared to similar populations in Israel and the USA. These results suggest that
a strong religious and spiritual identity may serve as a protective factor
against DEP.
PMID- 25138249
TI - Impaired left atrial function in heart failure with preserved ejection fraction.
AB - AIMS: Left atrial (LA) enlargement is present in the majority of heart failure
with preserved ejection fraction (HFpEF) patients and is a marker of risk.
However, the importance of LA function in HFpEF is less well understood. METHODS
AND RESULTS: The PARAMOUNT trial enrolled HFpEF patients (LVEF >=45%, NT-proBNP
>400 pg/mL). We assessed LA reservoir, conduit, and pump function using two
dimensional volume indices and speckle tracking echocardiography in 135 HFpEF
patients in sinus rhythm at the time of echocardiography and 40 healthy controls
of similar age and gender. Systolic LA strain was related to clinical
characteristics and measures of cardiac structure and function. Compared with
controls, HFpEF patients had worse LA reservoir, conduit, and pump function. The
differences in systolic LA strain (controls 39.2 +/- 6.6% vs. HFpEF 24.6 +/-
7.3%) between groups remained significant after adjustments and even in the
subsets of HFpEF patients with normal LA size or without a history of AF. Among
HFpEF patients, lower systolic LA strain was associated with higher prevalence of
prior HF hospitalization and history of AF, as well as worse LV systolic
function, and higher LV mass and LA volume. However, NT-proBNP and E/E' were
similar across the quartiles of LA function. CONCLUSIONS: In this HFpEF cohort,
we observed impairment in all phases of LA function, and systolic LA strain was
decreased independent of LA size or history of AF. LA dysfunction may be a marker
of severity and play a pathophysiological role in HFpEF. TRIAL REGISTRATION:
NCT00887588.
PMID- 25138251
TI - Angiopep-2 and activatable cell penetrating peptide dual modified nanoparticles
for enhanced tumor targeting and penetrating.
AB - Delivering chemotherapeutics by nanoparticles into tumor was influenced by at
least two factors: specific targeting and highly efficient penetrating of the
nanoparticles. In this study, two targeting ligands, angiopep-2 and activatable
cell penetrating peptide (ACP), were functionalized onto nanoparticles for tumor
targeting delivery. In this system, angiopep-2 is a ligand of low-density
lipoprotein receptor-related protein-1 (LRP1) which was highly expressed on tumor
cells, and the ACP was constructed by the conjugation of RRRRRRRR (R8) with
EEEEEEEE through a matrix metalloproteinase-2 (MMP-2) sensitive linker, enabling
the ACP with tumor microenvironment-responsive cell penetrating property. 4h
incubation of ACP with MMP-2 leads to over 80% cleavage of ACP, demonstrating ACP
indeed possessed MMP-2 responsive property. The constructed dual targeting
nanoparticles (AnACNPs) were approximately 110 nm with a polydispersity index of
0.231. In vitro, ACP modification and angiopep-2 modification could both enhance
the U-87 MG cell uptake because of the high expression of MMP-2 and LRP-1 on C6
cells. AnACNPs showed higher uptake level than the single ligand modified
nanoparticles. The uptake of all particles was time- and concentration-dependent
and endosomes were involved. In vivo, AnACNPs showed best tumor targeting
efficiency. The distribution of AnACNPs in tumor was higher than all the other
particles. After microvessel staining with anti-CD31 antibody, the fluorescent
distribution demonstrated AnACNPs could distribute in the whole tumor with the
highest intensity. In conclusion, a novel drug delivery system was developed for
enhanced tumor dual targeting and elevated cell internalization.
PMID- 25138250
TI - Enhancement in bioavailability of ketorolac tromethamine via intranasal in situ
hydrogel based on poloxamer 407 and carrageenan.
AB - The objective of this study was to construct a new in situ gel system based on
the combination of poloxamer 407 and carrageenan (carrageenan-poloxamer 407
hydrogel, CPH) for intranasal delivery of ketorolac tromethamine. CPH showed
potassium ion concentration - dependent erosion characteristics which ensured
slow erosion in aqueous environment containing potassium ion at the physiological
level. Loading with ketorolac tromethamine influenced erosion, drug release and
thermosensitive properties of CPH. CPH containing 15% ketorolac tromethamine
showed suitable gelation temperature (near 35 degrees C) and in vitro sustained
release profiles. Pharmacokinetic study of intranasal CPH containing 15%
ketorolac tromethamine in rats demonstrated enhanced absolute bioavailability
(68.8 +/- 23.3%) and prolonged mean residence time (8.8 +/- 3.5h) in comparison
with the intranasal solution group (24.8 +/- 13.8%, 3.9 +/- 0.6h). Nasal
ciliotoxicity evaluation on an in situ toad palate model preliminarily showed the
safety of CPH for intranasal use. All results suggested the potential of CPH as a
new sustained - release platform for the intranasal delivery of ketorolac
tromethamine.
PMID- 25138252
TI - Liposome-based co-delivery of siRNA and docetaxel for the synergistic treatment
of lung cancer.
AB - Combination of more than one therapeutic strategy is the standard treatment in
clinics. Co-delivery of chemotherapeutic drug and small interfering RNA (siRNA)
within a nanoparticulate system will suppress the tumor growth. In the present
study, docetaxel (DTX) and BCL-2 siRNA was incorporated in a PEGylated liposome
to systemically deliver in a lung cancer model (A549). The resulting nanoparticle
(lipo-DTX/siRNA) was stable and exhibited a sustained release profile. The co
delivery of therapeutic moieties inhibited the cell proliferation (A549 and H226)
in a time-dependent manner. Moreover, the co-delivery system of DTX and siRNA
exhibited a remarkable apoptosis of cancer cells with elevated levels of caspase
3/7 activity (apoptosis markers). Cell cycle analysis further showed remarkable
increase in sub-G0/G1 phase, indicating increasing hypodiploids or apoptotic
cells. Pharmacokinetic study showed a long circulating profile for DTX from lipo
DTX/siRNA system facilitating the passive tumor targeting. In vivo antitumor
study on A549 cell bearing xenograft tumor model exhibited a remarkable tumor
regression profile for lipo-DTX/siRNA with 100% survival rate. The favorable
tumor inhibition response was attributed to the synergistic effect of DTX potency
and MDR reversing ability of BCL-2 siRNA in the tumor mass. Overall, experimental
results suggest that co-delivery of DTX and siRNA could be promising approach in
the treatment of lung cancers.
PMID- 25138254
TI - Development of nanocrystal formulation of meloxicam with improved dissolution and
pharmacokinetic behaviors.
AB - The present study aimed to develop nanocrystal formulations of meloxicam (MEL) in
order to enhance its biopharmaceutical properties and provide a rapid onset of
action. Nanocrystal formulations were prepared by wet-milling and lyophilization
with hydrophilic polymers used as aggregation inhibitors. Aggregation inhibitors
were selected based on high-throughput screening of crystal growth inhibition in
supersaturated MEL solution. Supersaturation of MEL was observed in PVP K-30, HPC
SSL, and POVACOAT Type F solution. Although the particle size distributions of
pulverized MEL with PVP K-30 (MEL/PVP), HPC-SSL (MEL/HPC), and POVACOAT Type F
(MEL/POVA) were in the nanometer range following lyophilization, increases in
micron-sized aggregates were observed after storage at 60 degrees C for 21 days.
The order of increased amount of aggregates was MEL/POVA?MEL/HPC>MEL/PVP. These
findings showed that hydrophilic polymers that inhibited crystal growth in
supersaturated MEL solutions tended to prevent aggregation. The dissolution
behavior of all nanocrystal formulations tested was markedly enhanced compared
with that of unpulverized MEL. Oral administration of MEL/PVP showed a 2.0h
shortened Tmax and a 5.0-fold increase in bioavailability compared with
unpulverized MEL. These findings showed that the MEL/PVP mixture was
physicochemically stable and provided a rapid onset of action and enhanced
bioavailability after oral administration.
PMID- 25138253
TI - Hydroxypropyl-beta-cyclodextrin grafted polyethyleneimine used as transdermal
penetration enhancer of diclofenac sodium.
AB - The objective of this investigation was to develop a novel cationic polymer,
hydroxypropyl-beta-cyclodextrin grafted polyethyleneimine (HP-beta-CD-PEI1800),
as a penetration enhancer, and evaluate its viability on improving transdermal
delivery of diclofenac sodium. In this study, HP-beta-CD-PEI1800 was
characterized by (1)H NMR and DSC methods, respectively. The hydrophilic drug
diclofenac sodium was chosen as model drug, and the transdermal permeation
enhancement of HP-beta-CD-PEI1800 was estimated in vitro by using Franz diffusion
cells fitted with mouse dorsal skins, the in vivo kinetics of diclofenac sodium
was analyzed by high-performance liquid chromatography (HPLC). The cumulative
drug content deposited in epidermis and dermis was measured at the pre-determined
time point of 3, 6, and 9h, and the permeation profile was significantly higher
than that of the control groups. In addition, the cytotoxicity and skin
irritation of enhancer was evaluated by MTT assay and histological examination,
respectively, and the results indicated that the polymer we prepared were non
toxic and non-irritant after exposure to skins. All the results suggested that HP
beta-CD-PEI1800 could be a safe and efficient penetration enhancer of diclofenac
sodium.
PMID- 25138255
TI - Formulation and in vitro and in vivo evaluation of a cationic emulsion as a
vehicle for improving adenoviral gene transfer.
AB - Advancements in the use of adenoviral vectors in gene therapy have been limited
by the need for specific receptors on targeted cell types, immunogenicity and
hepatotoxicity following systemic administration. In an effort to overcome the
current limitations of adenovirus-mediated gene transfer, cationic emulsions were
explored as a vehicle to improve adenoviral vector-mediated gene transfer.
Complexation of adenovirus with emulsions containing the cationic lipid 1,2
dioleoyl-3-trimethylammonium propane (DOTAP) enhanced the potency of adenoviral
gene transfer as compared to DOTAP liposomes. Among the various emulsion
formulations examined, those containing the iodized oil, Lipiodol, as an inner
core and stabilized by DOTAP/cholesterol/1,2-distearoyl-sn-glycero-3
phosphoethanolamine-N-methoxy(poly-ethylene glycol)-5000 most efficiently
enhanced adenovirus-mediated gene transfer. Optimized Lipiodol-containing
emulsions appear to be more strongly associated with adenoviral particles,
exhibiting higher complex stability compared to other formulations. They provide
the adenovirus with an additional cellular entry mechanism through caveolae
dependent endocytosis, thereby increasing adenovirus entry into cells.
Furthermore, adenovirus-emulsion complexation significantly reduced transgene
expression in the liver following systemic administration. These findings
indicate that emulsion complexation may be a promising strategy for overcoming
many of the challenges associated with the use of adenoviruses in gene therapy.
Additionally, the observation of increased transgene expression in lung together
with reduced expression in liver demonstrates that the adenovirus-emulsion
complex may act as a lung-targeting adenoviral gene delivery system.
PMID- 25138256
TI - Amorphous isradipine nanosuspension by the sonoprecipitation method.
AB - The aims of this study are to increase and explain the mechanism of dissolution
enhancement of isradipine using the sonoprecipitation method for stable
nanosuspensions. There have been still few of published researches on formulation
of isradipine using nanoparticle engineering. Nanosuspension systems were
prepared upon various factors including amplitude and the time length of
ultrasonication. The dissolution test was performed according to the USP paddle
method in intestinal fluid (pH 6.8). The crystalline structure of drug, the
molecular interaction, morphology and size of nanosuspension were also
investigated to determine the mechanism of dissolution enhancement. The
sonoprecipitation method with use of HPMC 6 showed its potential in enhancement
of the drug release rate. Stable nanosuspension was significantly depended on
amplitude and time of ultrasonication since these factors affected on the size of
nanoparticles. The synergistic effects of reduction of drug crystallinity and
particle size could increase the dissolution rate of isradipine by providing a
stable nanosuspension. This work may contribute to a new strategy for improvement
dissolution rate of isradipine.
PMID- 25138257
TI - On the scaling behavior of electric conductivity in [C4mim][NTf2].
AB - In this work we examine, for the first time, the molar conductivity behavior of
the deeply supercooled room temperature ionic liquid [C4mim][NTf2] in the
temperature, pressure and volume thermodynamic space in terms of density scaling
(TV(gamma))(-1) combined with the equation of state (EOS). The exponent
gammasigma determined from the Avramov model analysis is compared with the
coefficient obtained from the viscosity studies carried out at moderate
temperatures. Therefore, the experimental results presented herein provide the
answer to the long-standing question regarding the validity of thermodynamic
scaling of ionic liquids over a wide temperature range, i.e. from the normal
liquid state to the glass transition point. Finally, we investigate the
relationship between the dynamic and thermodynamic properties of [C4mim][NTf2]
represented by scaling exponent gamma and Gruneisen constant gammaG,
respectively.
PMID- 25138258
TI - Reproductive interference between Rana dalmatina and Rana temporaria affects
reproductive success in natural populations.
AB - Experimental evidence suggests that reproductive interference between
heterospecifics can seriously affect individual fitness; support from field
studies for such an effect has, however, remained scarce. We studied reproductive
interference in 25 natural breeding ponds in an area where two ranid frogs, Rana
dalmatina and Rana temporaria, co-occur. The breeding seasons of the two species
usually overlap and males of both species are often found in amplexus with
heterospecific females, even though matings between heterospecifics produce no
viable offspring. We estimated species abundance ratios based on the number of
clutches laid and evaluated fertilization success. In ponds with low spatial
complexity and a species abundance ratio biased towards R. temporaria, the
average fertilization success of R. dalmatina eggs decreased, while this
relationship was not detectable in spatially more complex ponds. Fertilization
success of R. temporaria did not decrease with increasing relative numbers of
heterospecifics. This asymmetry in fitness effects of reproductive interference
may be attributed to R. temporaria males being more competitive in scramble
competition for females than R. dalmatina males. Our study is among the first to
demonstrate that in natural breeding populations of vertebrates interference
among heterospecifics has the potential to substantially lower reproductive
success at the population level, which may in turn affect population dynamics.
PMID- 25138260
TI - Epidemiology of forearm fractures in adults in Denmark: national age- and gender
specific incidence rates, ratio of forearm to hip fractures, and extent of
surgical fracture repair in inpatients and outpatients.
AB - National epidemiological studies of forearm fractures are scarce. We examined in-
and outpatient rates in Denmark, including anatomical location, surgery,
hospitalization ratio, recurrent fractures, and ratio of forearm to hip
fractures. This may be useful for triangulation in countries with less detailed
information. Rates were higher than previously estimated. INTRODUCTION: Despite a
significant contribution to the overall burden of osteoporotic, nonvertebral
fractures, relatively little information is available about age- and gender
specific incidence rates for many countries including Denmark. METHODS: We used
national individual patient data on inpatient and outpatient treatment to
calculate rates of forearm fractures, taking readmissions into account, with
subtables for distal and proximal fractures. We also calculated ratios of forearm
to hip fractures that may be useful when imputing forearm fracture rates from
other administrative sources. In addition, we report the rates of hospital
admission and the rates of surgical treatment, allowing readers to extrapolate
from the number of admissions or surgical procedures to incidence rates, should
their data sources be less comprehensive. RESULTS: Forearm fracture rates were
278 per 100,000 patient years in men aged 50+ and 1,110 per 100,000 in women aged
50+. The female to male incidence rate ratio was 4.0 for the age group 50+ but
close to unity in persons aged 40 or under. Two thirds of patients were treated
on an outpatient basis with little difference across age and gender strata. Four
out of five fractures were treated conservatively. The rate of forearm fractures
in Denmark was somewhat higher in both genders than recently imputed from hip
fracture rates and were close to the rates previously reported in studies from
Norway and Sweden. CONCLUSION: The rates of forearm fracture in Denmark are
higher than previously estimated and very similar to the high risk reported from
studies in Norway and Sweden.
PMID- 25138259
TI - Vitamin D and skeletal health in infancy and childhood.
AB - During growth, severe vitamin D deficiency in childhood can result in symptomatic
hypocalcaemia and rickets. Despite the suggestion from some studies of a secular
increase in the incidence of rickets, this observation may be driven more by
changes in population demographics than a true alteration to age, sex and
ethnicity-specific incidence rates; indeed, rickets remains uncommon overall and
is rarely seen in fair-skinned children. Additionally, the impact of less severe
vitamin D deficiency and insufficiency has received much interest in recent
years, and in this review, we consider the evidence relating vitamin D status to
fracture risk and bone mineral density (BMD) in childhood and adolescence. We
conclude that there is insufficient evidence to support the suggestion that low
serum 25-hydroxyvitamin D [25(OH)D] increases childhood fracture risk. Overall,
the relationship between 25(OH)D and BMD is inconsistent across studies and
across skeletal sites within the same study; however, there is evidence to
suggest that vitamin D supplementation in children with the lowest levels of
25(OH)D might improve BMD. High-quality randomised trials are now required to
confirm this benefit.
PMID- 25138262
TI - Serum levels of 25-hydroxyvitamin D and the occurrence of musculoskeletal
diseases: a 3-year follow-up to the road study.
AB - Assessment of serum 25-hydroxyvitamin D levels in association with the occurrence
of musculoskeletal diseases using a population-based cohort study design revealed
that serum 25-hydroxyvitamin D levels could predict the occurrence of
osteoporosis at the femoral neck within 3 years, but not the occurrence of knee
osteoarthritis or lumbar spondylosis. INTRODUCTION: The aim of this study is to
clarify the association between serum 25-hydroxyvitamin D (25D) levels and
occurrence of osteoporosis and osteoarthritis in the general population. METHODS:
The Research on Osteoarthritis/Osteoporosis Against Disability study, a large
scale population-based cohort study, was performed during 2005-2007. Serum 25D
levels were measured in 1,683 participants. Of these, 1,384 individuals (81.9%)
completed a second follow-up survey 3 years later. Osteoporosis was defined
according to World Health Organization criteria, in which osteoporosis is
diagnosed by T-scores of bone mineral density (BMD) that are 2.5 standard
deviations (SD) less than normal BMD. Knee osteoarthritis and lumbar spondylosis
were defined as Kellgren-Lawrence grade >=2, using paired X-ray films. Cumulative
incidences were determined according to changes in measurements using World
Health Organization criteria for osteoporosis or Kellgren-Lawrence grades for
osteoarthritis between the baseline and second survey. RESULTS: The mean (SD)
serum 25D level of the 1,384 participants in both surveys was 23.4 ng/mL (6.5).
The annual cumulative incidences of osteoporosis at L2-4 and the femoral neck
were 0.76 and 1.83%/year, respectively. The incidences of knee osteoarthritis and
lumbar spondylosis were 3.3 and 11.4%/year, respectively. After adjusting for
potential associated factors, logistic regression analyses revealed that the odds
ratio for the occurrence of femoral neck osteoporosis significantly decreased as
serum 25D levels increased (+1 SD; odds ratio 0.67; 95% confidence interval 0.49
0.92; p = 0.014). CONCLUSIONS: Higher serum 25D levels may prevent the occurrence
of osteoporosis at the femoral neck, but not knee osteoarthritis, lumbar
spondylosis, or osteoporosis at L2-4.
PMID- 25138261
TI - A systematic review on the use of daily subcutaneous administration of
teriparatide for treatment of patients with osteoporosis at high risk for
fracture in Asia.
AB - This systematic review aimed to examine the evidence for teriparatide in Asia for
osteoporosis with a high fracture risk and for exploratory (unapproved) bone
related indications. MEDLINE (1946+), EMBASE (1966+), and ClinicalTrials.gov
(2008+) were searched (16 August 2013); all studies of daily subcutaneous
teriparatide 20 MUg for bone-related conditions from China, Hong Kong, Japan,
Republic of Korea, Philippines, Singapore, and Taiwan were included. Evidence on
efficacy/safety was retrieved primarily from randomized controlled trials (10
publications) of postmenopausal women from Japan and China. In these studies,
teriparatide was well tolerated; subjects had significantly greater increases in
lumbar spine bone mineral density (BMD) from baseline compared with placebo,
antiresorptive agents, or elcatonin/calcitonin; bone turnover markers increased
from baseline and were sustained at elevated levels during teriparatide
treatment. Few studies reported fracture risk, pain, or quality of life; one
study showed a lower incidence of new-onset vertebral fracture with teriparatide
versus antiresorptive agents. Nonrandomized studies (nine publications, one
unpublished trial) conducted mainly in Taiwan, Japan, and the Republic of Korea
provided supporting data for efficacy. The exploratory (unapproved) use of
teriparatide (17 publications) for fracture healing and osteonecrosis of the jaw
was described primarily in case reports. The clinical effectiveness of
teriparatide for treatment of postmenopausal women with osteoporosis who are at
high risk of fracture in Asia is focused primarily on improvements in BMD and
tolerability. Recommended additional studies may include assessment of fracture
risk and the effect of teriparatide on pain, quality of life, and mortality in
Asia.
PMID- 25138263
TI - Postpartum osteoporosis and vertebral fractures in two patients treated with
enoxaparin during pregnancy.
AB - Postpartum osteoporosis (PPO) is a rare disease associated with pregnancy and
lactation period. Here, we report severe PPO and multiple vertebral compression
fractures in two patients treated with enoxaparin--low-molecular-weight heparin
(LMWH)--throughout their pregnancy. A 34-year-old woman who has delivered her
second baby 3 months ago presented with severe low-back pain. She was treated
with enoxaparin 40 mg/day for 8 months during her pregnancy. Dual-energy X-ray
absorptiometry (DEXA) showed low T- and Z-scores in lumbar (L) vertebras. In
magnetic resonance imaging (MRI), severe height losses in thoracic (T) 12, L1,
and L2 vertebras were detected. She was diagnosed to have severe PPO and multiple
vertebral compression fractures and was prescribed risedronate 35 mg/week,
calcium, and vitamin D. The other patient was a 36-year-old woman diagnosed with
PPO and vertebral fractures at the third week postpartum. She was also treated
with enoxaparin 60 mg/day during her pregnancy. Severe osteoporosis in L
vertebras and height losses indicative for compression fractures in T5-8, T11-12,
and L2-5 vertebras were detected by DEXA and MRI, respectively. She was treated
with calcitonin 200 U/day, calcium, and vitamin D. These findings suggest that
vertebral compression fractures and PPO may be one of the causes of severe back
pain in postpartum patients. Treatment with LMWH during pregnancy might be
considered as a new risk factor for this rare condition.
PMID- 25138264
TI - Polymorphisms in genes in the RANKL/RANK/OPG pathway are associated with bone
mineral density at different skeletal sites in post-menopausal women.
AB - Association between 22 single nucleotide polymorphisms (SNPs) in the TNFSF11,
TNFRSF11A, and TNFRSF11B genes in the RANKL/RANK/OPG pathway with bone mineral
density (BMD) in 881 post-menopausal women. Our results suggest that TNFSF11 and
TNFRSF11A, but not TNFRSF11B, genetic polymorphisms influence BMD mainly in the
femoral neck in post-menopausal Chinese women. INTRODUCTION: The aim of this
study was to assess the relationship of polymorphisms in the TNFSF11, TNFRSF11A,
and TNFRSF11B genes in the RANKL/RANK/OPG pathway with bone mineral density (BMD)
in a cohort of Chinese post-menopausal women. METHODS: A cross-sectional study
was conducted in 881 post-menopausal women aged 50-89 years. All participants
underwent lumbar spinal (LS) and femoral neck (FN) BMD evaluation by dual-energy
X-ray absorptiometry. Twenty-two TNFSF11, TNFRSF11A, and TNFRSF11B SNPs were
genotyped. We tested whether a single SNP or a haplotype was associated with BMD
variations. RESULTS: Two SNPs in the TNFSF11 gene (rs2277439 and rs2324851) and
one in the TNFRSF11A gene (rs7239261) were found to be significantly associated
with FN BMD (p = 0.014, 0.013, and 0.047, respectively). Haplotype TGACGT of
TNFSF11 rs9525641-rs2277439-rs2324851-rs2875459-rs2200287-rs9533166 was a genetic
risk factor toward a lower FN BMD (beta = -0.1473; p = 0.01126). In contrary,
haplotype TAGCGT of TNFSF11 rs9525641-rs2277439-rs2324851-rs2875459-rs2200287
rs9533166 was genetic protective factor for LS BMD (beta = 0.3923; p = 0.04917).
CONCLUSIONS: Our findings suggest that TNFSF11 and TNFRSF11A, but not TNFRSF11B,
genetic polymorphisms influence BMD mainly in the femoral neck in post-menopausal
Chinese women. This contributes to the understanding of the role of genetic
variation in this pathway in determining bone health.
PMID- 25138266
TI - Basophil activation test in wasp venom allergy during mastocytosis.
PMID- 25138265
TI - Effects of vitamin D supplementation on neuroplasticity in older adults: a double
blinded, placebo-controlled randomised trial.
AB - Vitamin D can improve muscle function and reduce falls, but whether it can
strengthen neural connections within the brain and nervous system is not known.
This 10-week randomised controlled trial indicates that treatment with 2,000
IU/day vitamin D3 does not significantly alter neuroplasticity relative to
placebo in older adults. INTRODUCTION: The purpose of this study was to examine
the effects of vitamin D supplementation on neuroplasticity, serum brain-derived
neurotrophic factor (BDNF) and muscle strength and function in older adults.
METHODS: This was a 10-week double-blinded, placebo-controlled randomised trial
in which 26 older adults with 25-hydroxyvitamin D [25OHD] concentrations 25-60
nmol/L were randomised to 2,000 IU/day vitamin D3 or matched placebo. Single- and
paired-pulse transcranial magnetic stimulation applied over the motor cortex was
used to assess changes in motor-evoked potentials (MEPs) and short-interval
intracortical inhibition (SICI), as measures of corticospinal excitability and
inhibition respectively, by recording electromyography (EMG) responses to
stimulation from the wrist extensors. Changes in muscle strength, stair climbing
power, gait (timed-up-and-go), dynamic balance (four square step test), serum
25(OH)D and BDNF concentrations were also measured. RESULTS: After 10 weeks, mean
25(OH)D levels increased from 46 to 81 nmol/L in the vitamin D group with no
change in the placebo group. The vitamin D group experienced a significant 8-11%
increase in muscle strength and a reduction in cortical excitability (MEP
amplitude) and SICI relative to baseline (all P < 0.05), but these changes were
not significantly different from placebo. There was no effect of vitamin D on
muscle power, function or BDNF. CONCLUSIONS: Daily supplementation with 2,000 IU
vitamin D3 for 10 weeks had no significant effect on neuroplasticity compared to
placebo, but the finding that vitamin D treatment alone was associated with a
decrease in corticospinal excitability and intracortical inhibition warrants
further investigation as this suggests that it may improve the efficacy of neural
transmission within the corticospinal pathway.
PMID- 25138267
TI - beta-Glucosidase BGLU42 is a MYB72-dependent key regulator of rhizobacteria
induced systemic resistance and modulates iron deficiency responses in
Arabidopsis roots.
AB - Selected soil-borne rhizobacteria can trigger an induced systemic resistance
(ISR) that is effective against a broad spectrum of pathogens. In Arabidopsis
thaliana, the root-specific transcription factor MYB72 is required for the onset
of ISR, but is also associated with plant survival under conditions of iron
deficiency. Here, we investigated the role of MYB72 in both processes. To
identify MYB72 target genes, we analyzed the root transcriptomes of wild-type Col
0, mutant myb72 and complemented 35S:FLAG-MYB72/myb72 plants in response to ISR
inducing Pseudomonas fluorescens WCS417. Five WCS417-inducible genes were
misregulated in myb72 and complemented in 35S:FLAG-MYB72/myb72. Amongst these, we
uncovered beta-glucosidase BGLU42 as a novel component of the ISR signaling
pathway. Overexpression of BGLU42 resulted in constitutive disease resistance,
whereas the bglu42 mutant was defective in ISR. Furthermore, we found 195 genes
to be constitutively upregulated in MYB72-overexpressing roots in the absence of
WCS417. Many of these encode enzymes involved in the production of iron
mobilizing phenolic metabolites under conditions of iron deficiency. We provide
evidence that BGLU42 is required for their release into the rhizosphere.
Together, this work highlights a thus far unidentified link between the ability
of beneficial rhizobacteria to stimulate systemic immunity and mechanisms induced
by iron deficiency in host plants.
PMID- 25138268
TI - Combined Y-shaped common channel transureteroureterostomy with Boari flap to
treat bilateral long-segment ureteral strictures.
AB - BACKGROUND: Ureteral stricture is a complication of several etiologies including
idiopathic retroperitoneal fibrosis, infection, radiotherapy, instrumentation,
and surgical procedures. A variety of techniques have been reported for
management. The transureteroureterostomy and bladder flap have been the standard
procedures for repairing distal ureteral defects of unilateral ureter. Bilateral
ureteral stricture is an uncommon condition that challenges usual reconstructive
procedures. It is a difficult task to reconstruct the complex situation of
bilateral ureteral strictures. CASE PRESENTATION: A 54-year-old female underwent
concurrent chemoradiotherapy for stage IVB squamous cell carcinoma of cervix.
Subsequently, she had stricture of bilateral distal ureters with bilateral
hydroureteronephrosis which was found by computed tomography. The renal function
deteriorated during the follow-up period. She had periodic change of double-J
stents and percutaneous nephrostomy. However, the renal function still
deteriorated. We performed a combined Y-shaped common channel
transureteroureterostomy with Boari flap to reconstruct bilateral long-segment
ureteral strictures. The patient recovered uneventfully. CONCLUSION:
Reconstruction of bilateral ureteral strictures is a difficult treatment. We
developed a modified technique for the complex situation of bilateral ureteral
strictures. To our knowledge, this has not been previously reported in the
scientific literature and it is a feasible procedure to treat bilateral long
segment ureteral strictures.
PMID- 25138269
TI - Why did the proton cross the road? Humour and science communication.
AB - The use of humour in public discourse about science has grown remarkably over the
past few years, and when used in science communication activities is being seen
as a great way to bring science to the public through laughter. However, barely
any research has been published either on the often-assumed beneficial learning
effects of humour in informal science education, or on the wider social functions
and effects of humour about science and how humorous public discourse about
science can influence the public understanding of science and the science-society
relationship. This research note reviews some of the literature on the psychology
and sociology of humour and comedy and tries to apply some of its insights to the
effects humour might have when used in science communication. Although not
intended to be anti-humour, this note attempts at least to start a more critical
conversation on the value of humour in the communication of science.
PMID- 25138270
TI - A first-principles investigation of the stabilities and electronic properties of
SrZrO3 (1 1 0) (1 * 1) polar terminations.
AB - The stabilities and electronic properties of SrZrO3 (1 1 0) (1 * 1) polar
terminations were investigated systematically by the first-principles density
functional theory method. Five possible polar surfaces, i.e. O-deficient, O-rich,
stoichiometric, SrO-rich and SrO-deficient ones, were considered. The calculated
results indicated that the charge neutralization and polarity compensation
condition could be achieved by charge redistributions of surface atoms. For the O
deficient (1 1 0) termination, some filled electronic states were separated from
the original conduction bands, while a surface reconstruction was found for the O
rich (1 1 0) surface. The remaining three (1 1 0) terminations remained
insulated. Furthermore, a stability diagram involving seven different
terminations was constructed using the surface grand potential technique, in
which the effect of the chemical environment was included. The calculated results
indicated that three (1 1 0) (O-rich, SrO-rich and stoichiometric) and 2 (0 0 1)
(ZrO2 and SrO) terminations could be stabilized in distinct areas, whereas the O
deficient surface was unstable within the whole region. Finally, we drew a
comparison of stability behaviors between SrZrO3 (1 1 0) (1 * 1) polar surfaces
and the counterparts of ATiO3 (A = Ba, Pb, Sr) and BaZrO3 materials.
PMID- 25138271
TI - Extraprostatic extension (EPE) of prostatic carcinoma: is its proximity to the
surgical margin or Gleason score important?
AB - OBJECTIVE: To examine the association between histopathological factors of
extraprostatic prostate cancer and outcome. PATIENTS AND METHODS: Patients with
extraprostatic extension (EPE) without positive margins, seminal vesicle or lymph
node involvement were analysed from a consecutive radical prostatectomy cohort of
1136 (2002-2006) for: (i) distance of EPE from the margin; (ii) Gleason score of
the EPE; and (iii) extent of EPE. Log-rank, Kaplan-Meier, and Cox regression
analyses were performed. RESULTS: The study included 194 pT3a, pN0, R0 patients
with a median follow-up of 5.4 years, with 37 (19%) patients experiencing
biochemical relapse (BCR). On univariable analysis, patients with a Gleason score
of >=8 in the extraprostatic portion showed increased incidence of BCR compared
with those with Gleason scores of <=7 (P = 0.03). The proximity of the EPE to the
margin (0.01-7.5 mm) did not correlate with BCR. On multivariable analysis, the
extent of EPE, the Gleason score of the dominant nodule or of the EPE portion did
not correlate with BCR. CONCLUSION: Data from this study using current
International Society of Urological Pathology Gleason scoring and EPE criteria
indicate that close proximity of EPE to the margin is not associated with
recurrence. Gleason score >=8 within EPE is associated with an increased BCR risk
on univariable analysis, but larger studies are required to confirm whether
extensive Gleason pattern 4 in an EPE indicates increased risk in an otherwise
overall Gleason score 7 cancer.
PMID- 25138272
TI - Etanercept restores normal insulin signal transduction in beta2-adrenergic
receptor knockout mice.
AB - BACKGROUND: Inhibition of TNFalpha protects the retina against diabetic-like
changes in rodent models. The mechanism by which TNFalpha induces deleterious
retinal changes is not known. Previously, we have shown that TNFalpha can inhibit
normal insulin signal transduction, leading to increased apoptosis in both
retinal endothelial cells (REC) and Muller cells. Additionally, beta2-adrenergic
receptor knockout mice (beta2KO) have increased TNFalpha levels and decreased
insulin receptor activity. In this study, we hypothesized that inhibition of
TNFalpha in beta2KO mice would increase normal insulin signaling, leading to
improved retinal function. METHODS: C57BL6 or beta2KO mice were left untreated or
treated with etanercept (0.3 mg/kg subcutaneously, 3* a week) for 2 months.
Electroretinogram analyses were done before treatment was initiated and after two
months of treatment with etanercept on all mice. Western blot or ELISA analyses
were done on whole retinal lysates from all four groups of mice for TNFalpha,
suppressor of cytokine signaling 3 (SOCS3), insulin receptor, and apoptotic
proteins. RESULTS: Etanercept significantly reduced TNFalpha levels in beta2KO
mice, leading to increased insulin receptor phosphorylation on tyrosine
1150/1151. SOCS3 levels were increased in beta2KO mice, which were reduced after
etanercept treatment. Pro-apoptotic proteins were reduced in etanercept-treated
beta2KO mice. Etanercept improved ERG amplitudes in beta2KO mice. CONCLUSIONS:
Inhibition of TNFalpha by etanercept protects the retina likely through reduced
TNFalpha-mediated insulin resistance, leading to reduced apoptosis.
PMID- 25138273
TI - Continuous transversus abdominis plane (TAP) blocks for postoperative pain
control after hernia surgery: a randomized, triple-masked, placebo-controlled
study.
AB - BACKGROUND: Single-injection transversus abdominis plane (TAP) block provides
postoperative analgesia and decreases supplemental analgesic requirements.
However, there is currently no evidence from randomized, controlled studies
investigating the possible benefits of continuous TAP blocks. Therefore, the aim
of this randomized, triple-masked, placebo-controlled study was to determine if
benefits are afforded by adding a multiple-day, ambulatory, continuous
ropivacaine TAP block to a single-injection block following hernia surgery.
METHODS: Preoperatively, subjects undergoing unilateral inguinal (N=19) or peri
umbilical (N=1) hernia surgery received unilateral or bilateral TAP perineural
catheter(s), respectively. All received a ropivacaine 0.5% (20 mL) bolus via the
catheter(s). Subjects were randomized to either postoperative perineural
ropivacaine 0.2% or normal saline using portable infusion pump(s). Subjects were
discharged home where the catheter(s) were removed the evening of postoperative
day (POD) 2. Subjects were contacted on POD 0-3. The primary endpoint was average
pain with movement (scale: 0-10) queried on POD 1. RESULTS: Twenty subjects of a
target 30 were enrolled due to the primary surgeon's unanticipated departure from
the institution. Average pain queried on POD 1 for subjects receiving ropivacaine
(N=10) was a mean (standard deviation) of 3.0 (2.6) vs 2.8 (2.7) for subjects
receiving saline (N=10; 95% confidence interval difference in means -2.9 to 3.4;
P=0.86). There were no statistically significant differences detected between
treatment groups in any secondary endpoint. CONCLUSIONS: The results of this
study do not support adding an ambulatory, continuous ropivacaine infusion to a
single-injection ropivacaine TAP block for hernia surgery. However, the present
investigation was underpowered, and further study is warranted.
PMID- 25138276
TI - Highly oriented polymer semiconductor films compressed at the surface of ionic
liquids for high-performance polymeric organic field-effect transistors.
AB - A novel and versatile method to align polymer semiconductors is demonstrated.
Spreading and subsequent mechanical compression of a polymer thin film on an
ionic liquid's surface yield a polymer thin film that has high uniaxial
orientation of the polymer backbone, which is tested for typical polymer
semiconductors of PB16TTT, PNDTBTC20, and P3HT. TFTs fabricated by the method
exhibit significantly higher mobility compared to TFTs fabricated using a
conventional spin-coating process.
PMID- 25138274
TI - Nuclear factor I-C (NFIC) regulates dentin sialophosphoprotein (DSPP) and E
cadherin via control of Kruppel-like factor 4 (KLF4) during dentinogenesis.
AB - Odontoblasts are a type of terminally differentiated matrix-secreting cells. A
number of molecular mechanisms are involved in the differentiation of
odontoblasts. Several studies demonstrated that Kruppel-like factor 4 (KLF4)
promotes odontoblast differentiation via control of dentin sialophosphoprotein
(DSPP). Because nuclear factor I-C (NFIC) is also known to control DSPP, we
investigated the relationship between NFIC and KLF4 during odontoblast
differentiation. Klf4 mRNA expression was significantly decreased in Nfic(-/-)
pulp cells compared with wild type cells. In immunohistochemistry assays, dentin
matrix protein 1 (Dmp1), and DSP protein expression was barely observed in Nfic(
/-) odontoblasts and dentin matrix. Nfic bound directly to the Klf4 promoter and
stimulated Klf4 transcriptional activity, thereby regulating Dmp1 and DSPP
expression during odontoblast differentiation. Nfic or Klf4 overexpression
promoted mineralized nodule formation in MDPC-23 cells. In addition, Nfic
overexpression also decreased Slug luciferase activity but augmented E-cadherin
promoter activity via up-regulation of Klf4 in odontoblasts. Our study reveals
important signaling pathways during dentinogenesis: the Nfic-Klf4-Dmp1-Dspp and
the Nfic-Klf4-E-cadherin pathways in odontoblasts. Our results indicate the
important role of NFIC in regulating KLF4 during dentinogenesis.
PMID- 25138277
TI - Agar-supported cultivation of Halorubrum sp. SSR, and production of halocin C8 on
the scale-up prototype Platotex.
AB - Halorubrum sp. SSR was isolated from a solar saltern in Algeria. The strain
exhibited a high antibiotic activity against the indicator strain Natronorubrum
aibiense G23, and the bioactive compound showed thermal, acid and alkali
stability. SSR was grown on agar-supported cultivation (AgSF) to compare yields
and applicability with traditional submerged cultivation. AgSF scale-up was
implemented taking benefit from the solid-state cultivation prototype Platotex.
This technology leads to high amounts of the target Halocin and facilitate the
downstream steps. The antibiotic compound was purified according to a fast
efficient procedure including ion exchange chromatography followed by a
fractionation on C18 Sep-Pack cartridge. The compound was identified as Halocin
C8 according to N-terminal amino acid sequencing and high-resolution mass
spectrometry.
PMID- 25138275
TI - Endogenous glucuronyltransferase activity of LARGE or LARGE2 required for
functional modification of alpha-dystroglycan in cells and tissues.
AB - Mutations in the LARGE gene have been identified in congenital muscular dystrophy
(CMD) patients with brain abnormalities. Both LARGE and its paralog, LARGE2 (also
referred to as GYLTL1B) are bifunctional glycosyltransferases with
xylosyltransferase (Xyl-T) and glucuronyltransferase (GlcA-T) activities, and are
capable of forming polymers consisting of [-3Xyl-alpha1,3GlcAbeta1-] repeats.
LARGE-dependent modification of alpha-dystroglycan (alpha-DG) with these
polysaccharides is essential for the ability of alpha-DG to act as a receptor for
ligands in the extracellular matrix. Here we report on the endogenous enzymatic
activities of LARGE and LARGE2 in mice and humans, using a newly developed assay
for GlcA-T activity. We show that normal mouse and human cultured cells have
endogenous LARGE GlcA-T, and that this activity is absent in cells from the
Large(myd) (Large-deficient) mouse model of muscular dystrophy, as well as in
cells from CMD patients with mutations in the LARGE gene. We also demonstrate
that GlcA-T activity is significant in the brain, heart, and skeletal muscle of
wild-type and Large2(-/-) mice, but negligible in the corresponding tissues of
the Large(myd) mice. Notably, GlcA-T activity is substantial, though reduced, in
the kidneys of both the Large(myd) and Large2(-/-) mice, consistent with the
observation of alpha-DG/laminin binding in these contexts. This study is the
first to test LARGE activity in samples as small as cryosections and, moreover,
provides the first direct evidence that not only LARGE, but also LARGE2, is vital
to effective functional modification of alpha-DG in vivo.
PMID- 25138278
TI - Spatial distribution of diatom and cyanobacterial mats in the Dead Sea is
determined by response to rapid salinity fluctuations.
AB - Cyanobacteria and diatom mats are ubiquitous in hypersaline environments but have
never been observed in the Dead Sea, one of the most hypersaline lakes on Earth.
Here we report the discovery of phototrophic microbial mats at underwater
freshwater seeps in the Dead Sea. These mats are either dominated by diatoms or
unicellular cyanobacteria and are spatially separated. Using in situ and ex situ
O2 microsensor measurements we show that these organisms are photosynthetically
active in their natural habitat. The diatoms, which are phylogenetically
associated to the Navicula genus, grew in culture at salinities up to 40 % Dead
Sea water (DSW) (14 % total dissolved salts, TDS). The unicellular cyanobacteria
belong to the extremely halotolerant Euhalothece genus and grew at salinities up
to 70 % DSW (24.5 % TDS). As suggested by a variable O2 penetration depth
measured in situ, the organisms are exposed to drastic salinity fluctuations
ranging from brackish to DSW salinity within minutes to hours. We could
demonstrate that both phototrophs are able to withstand such extreme short-term
fluctuations. Nevertheless, while the diatoms recover better from rapid
fluctuations, the cyanobacteria cope better with long-term exposure to DSW. We
conclude that the main reason for the development of these microbial mats is a
local dilution of the hypersaline Dead Sea to levels allowing growth. Their
spatial distribution in the seeping areas is a result of different recovery rates
from short or long-term fluctuation in salinity.
PMID- 25138279
TI - The saci_2123 gene of the hyperthermoacidophile Sulfolobus acidocaldarius encodes
an ATP-binding cassette multidrug transporter.
AB - Multidrug resistance (MDR) transporters are capable of secreting structurally and
functionally unrelated toxic compounds from the cell. Among this group are ATP
binding cassette (ABC) transporters. These membrane proteins are typically
arranged as either hetero- or homo-dimers of ABC half-transporters with each
subunit consisting of a membrane domain fused at the C-terminus to an ATP-binding
domain, or as full transporters in which the two subunits are fused into a single
polypeptide. The saci_2123 gene of the thermoacidophilic archaeon Sulfolobus
acidocaldarius is the only gene in the genome that encodes an ATP-binding
cassette half-transporter, while a homologous gene is present in the genomes of
S. solfataricus, S. tokodaii and S islandicus. Saci_2123 shares homology with
well-characterized bacterial and mammalian MDR transporters. The saci_2132 gene
is up-regulated when cells are exposed to drugs. A deletion mutant of saci_2132
was found to be more vulnerable to a set of toxic compounds, including
detergents, antibiotics and uncouplers as compared to the wild-type strain, while
the drug resistance could be restored through the plasmid-based expression of
saci_2132. These data demonstrate that Saci_2132 is an archaeal ABC-MDR
transporter and therefore it was termed Smr1 (Sulfolobus multidrug resistance
transporter 1).
PMID- 25138281
TI - Dual role of Tlx3 as modulator of Prrxl1 transcription and phosphorylation.
AB - The proper establishment of the dorsal root ganglion/spinal cord nociceptive
circuitry depends on a group of homeodomain transcription factors that includes
Prrxl1, Brn3a and Tlx3. By the use of epistatic analysis, it was suggested that
Tlx3 and Brn3a, which highly co-localize with Prrxl1 in these tissues, are
required to maintain Prrxl1 expression. Here, we report two Tlx3-dependent
transcriptional mechanisms acting on Prrxl1 alternative promoters, referred to as
P3 and P1/P2 promoters. We demonstrate that (i) Tlx3 induces the transcriptional
activity of the TATA-containing promoter P3 by directly binding to a bipartite
DNA motif and (ii) it synergistically interacts with Prrxl1 by indirectly
activating the Prrxl1 TATA-less promoters P1/P2 via the action of Brn3a. The Tlx3
N-terminal domain 1-38 was shown to have a major role on the overall Tlx3
transcriptional activity and the C-terminus domain (amino acids 256-291) to
mediate the Tlx3 effect on promoters P1/P2. On the other hand, the 76-111 domain
was shown to decrease Tlx3 activity on the TATA-promoter P3. In addition to its
action on Prrxl1 alternative promoters, Tlx3 proved to have the ability to induce
Prrxl1 phosphorylation. The Tlx3 domain responsible for Prrxl1
hyperphosphorylation was mapped and encompasses amino acid residues 76 to 111.
Altogether, our results suggest that Tlx3 uses distinct mechanisms to tightly
modulate Prrxl1 activity, either by controlling its transcriptional levels or by
increasing Prrxl1 phosphorylation state.
PMID- 25138282
TI - Enrichment options for African painted dogs (Lycaon pictus).
AB - Best practices for carnivore enrichment encourage the diversity of species
typical behaviors, increased activity, and reduced stereotypic behavior; ideally
considering the life-history and behavior of each species. African wild dogs
(Lycaon pictus), or painted dogs, are social carnivores that have large home
ranges and complex pack dynamics (e.g., variation in group size, relatedness,
etc.). As there are relatively few studies on painted dog enrichment, the goal of
this study was to compile a list of enrichment options used by institutions
participating in the species survival plan (SSP). Representatives were asked to
describe social groups (n = 45), enclosures (n = 21), enrichment practices
(options, delivery frequency, perceived success), and overall best practices.
Respondents (61%, n = 23) reported using options for all six enrichment
categories recommended by the Canid Taxon Advisory Group: environmental
enrichment devices, habitat, sensory, food, behavioral, and social. Perceived
success was significantly higher for the food category, followed by the sensory
and behavioral categories. All respondents reported delivering enrichment at
least multiple times a month, and most reported multiple times per week.
Enclosure size did not differ significantly for mixed-sex groups (n = 28)
compared to single-sex groups (n = 17). We discuss respondents' suggestions for
best practices and the need to record data to compare perceived success with
actual behavioral effects, controlling for variation in group size and
composition. Overall, respondents recommended a flexible approach, since not all
painted dogs and groups respond in the same way to the enrichment options.
PMID- 25138284
TI - Scandium carbide/cyanide alloyed cluster inside fullerene cage: synthesis and
structural studies of Sc3(MU3-C2)(MU3-CN)@Ih-C80.
AB - A new Sc3(C2)(CN)@Ih-C80 metallofullerene encaging a scandium carbide/cyanide
alloyed cluster was prepared and investigated. Sc3(C2)(CN)@Ih-C80 was synthesized
by the arc-discharging method and isolated by HPLC. Its experimental (13)C NMR
spectrum with two signals clearly confirms an icosahedral C80 cage, and
theoretically calculated (13)C NMR peaks agree well with the experimental
results. Further, theoretical calculations disclosed that the endohedral MU3-C2
and MU3-CN moieties are situated on each side of the triangular shaped Sc3 unit
to form a scandium carbide/cyanide alloyed cluster. Kohn-Sham molecular orbitals
reveals the electronic structure of (Sc(3+))3(C2)(2-)(CN)(-)@C80(6-), in which
two anions, MU3-C2(2-) and MU3-(CN)(-), construct and stabilize this special
molecule together. The FTIR and Raman spectra of Sc3(C2)(CN)@Ih-C80 were analyzed
by comparison of the experimental and calculated results to further confirm its
structure and to uncover cluster-based vibrational modes.
PMID- 25138283
TI - Double-clicking peptides onto phosphorothioate oligonucleotides: combining two
proapoptotic agents in one molecule.
AB - Described here is a method for the conjugation of phosphorothioate
oligonucleotides (PSOs) with peptides. PSOs are key to antisense technology.
Peptide-PSO conjugates may improve target specificity, tissue distribution, and
cellular uptake of PSOs. However, the highly nucleophilic phosphorothioate
structure poses a challenge to conjugation chemistry. Herein, we introduce a new
method which involves a sequence of oxime ligation and strain-promoted [2+3]
cycloaddition. The usefulness of the method was demonstrated in the synthesis of
peptide-PSO conjugates that targeted two suppressors of both the intrinsic and
the extrinsic pathway of apoptosis. It is shown that the activity of a PSO
sequence targeted against mRNA from c-Flip can be enhanced by conjugation with a
peptide mimetic designed to inhibit the X-linked inhibitor of apoptosis protein
(XIAP).
PMID- 25138285
TI - Neuroimaging features in C9orf72 and TARDBP double mutation with FTD phenotype.
AB - Increasing evidence has shown that morphological and functional neuroimaging may
help to understand the pathophysiological mechanisms leading to behavioral
disturbances in patients with genetic or sporadic frontotemporal dementia (FTD).
The C9orf72 expansion was found in association with the N267S TARDBP mutation in
two siblings with behavioral-variant FTD (bvFTD). In one of them with very mild
dementia, MRI showed symmetric atrophy of temporal, inferolateral and orbital
frontal cortex, while [18F]FDG-PET disclosed more extended hypometabolism in
dorsolateral and inferolateral frontal cortex, anterior cingulate, and caudate
nucleus. Hypometabolism in right lateral and orbital frontal cortex was confirmed
also in comparison with a group of sporadic bvFTD patients. These findings appear
as the neuroimaging hallmark of double C9orf72 and TARDBP gene mutation with a
bvFTD phenotype.
PMID- 25138280
TI - The chicken chorioallantoic membrane model in biology, medicine and
bioengineering.
AB - The chicken chorioallantoic membrane (CAM) is a simple, highly vascularized
extraembryonic membrane, which performs multiple functions during embryonic
development, including but not restricted to gas exchange. Over the last two
decades, interest in the CAM as a robust experimental platform to study blood
vessels has been shared by specialists working in bioengineering, development,
morphology, biochemistry, transplant biology, cancer research and drug
development. The tissue composition and accessibility of the CAM for experimental
manipulation, makes it an attractive preclinical in vivo model for drug screening
and/or for studies of vascular growth. In this article we provide a detailed
review of the use of the CAM to study vascular biology and response of blood
vessels to a variety of agonists. We also present distinct cultivation protocols
discussing their advantages and limitations and provide a summarized update on
the use of the CAM in vascular imaging, drug delivery, pharmacokinetics and
toxicology.
PMID- 25138286
TI - Importance of branched-chain amino acids in patients with liver cirrhosis and
advanced hepatocellular carcinoma receiving hepatic arterial infusion
chemotherapy.
AB - PURPOSE: The aim of this retrospective cohort study was to clarify the effect of
a branched-chain amino acids (BCAA) on the liver function and the prognosis of
Child-Pugh class (C-P) A and B liver cirrhosis (LC) patients with advanced
hepatocellular carcinoma (aHCC) undergoing hepatic arterial infusion chemotherapy
(HAIC). METHODS: Ninety-two adult Japanese patients with LC and aHCC underwent
HAIC. They were in C-P A or B, and they showed multiple partial responses or
stable disease. We excluded 11 patients classified as C-P C and 47 patients who
showed no response. The patients were divided into an HAIC group receiving HAIC
alone (n = 43) and a BCAA group treated with HAIC plus BCAA (n = 49). HAIC was
delivered via the proper hepatic artery. The BCAA group also received oral
administration of BCAA. RESULTS: In the BCAA group, serum albumin increased
significantly after HAIC, while there were no significant changes in serum total
bilirubin, serum aminotransferases, prothrombin time, ascites, and hepatic
encephalopathy. The C-P score decreased significantly after HAIC compared with
before HAIC in C-P B patients, although there was no significant change in C-P A
patients. Survival of the BCAA group was significantly longer than that of the
HAIC group, with the median survival time being 426 versus 272 days for C-P B
patients, although there was no significant difference for C-P A patients.
CONCLUSIONS: Branched-chain amino acids might improve the survival and C-P score
by increasing serum albumin in C-P B patients with aHCC receiving HAIC.
PMID- 25138288
TI - Yb/Er co-doped phosphate all-solid single-mode photonic crystal fiber.
AB - An all-solid Yb(3+)/Er(3+) co-doped single-mode phosphate photonic crystal fiber
(PCF) with Watt-level output power and 20 MUm core diameter is demonstrated for
the first time. A PCF whose refractivity of the active core is lower than that of
the background glass is suggested and theoretically confirmed to be in single
mode operation at 40 MUm core diameter.
PMID- 25138287
TI - Patterns of change in implementation of state alcohol control policies in the
United States, 1999-2011.
AB - AIMS: To examine state alcohol control policy implementation by policy efficacy
and intent. DESIGN: A descriptive longitudinal analysis of policy implementation.
SETTING: The United States, 1999-2011. PARTICIPANTS: Fifty states and the
District of Columbia. MEASUREMENTS: Twenty-nine state-level policies were rated
based on an implementation rating (IR; range = 0.0-1.0) gathered from the Alcohol
Policy Information System, government and industry reports and other sources; and
expert judgment about policy efficacy for addressing binge drinking and alcohol
impaired driving among the general population and youth, respectively. FINDINGS:
On average, implementation of the most effective general population policies did
not change [mean IR = 0.366 in 1999; 0.375 in 2011; slope for annual change =
0.001; 95% confidence interval (CI) for the slope -0.001, 0.002]. In contrast,
implementation increased over time for less effective policies (mean IR = 0.287
in 1999; 0.427 in 2011; slope for annual change compared with most effective
policies = 0.009; slope 95% CI = 0.002-0.007), for youth-oriented policies (mean
IR = 0.424 in 1999; 0.511 in 2011; slope for annual change compared with most
effective policies = 0.007; slope 95% CI = 0.005-0.009), and for impaired driving
policies (mean IR = 0.493 in 1999; 0.608 in 2011; slope for annual change
compared with most effective policies = 0.0105; slope 95% CI = 0.007-0.014).
CONCLUSIONS: Implementation of politically palatable state alcohol policies, such
as those targeting youth and alcohol-impaired driving, and less effective
policies increased during 1999-2011 in the United States, while the most
effective policies that may maximally protect public health remained underused.
PMID- 25138290
TI - Evaluation and validation of a serum bactericidal antibody assay for Haemophilus
influenzae type b and the threshold of protection.
AB - Prior to routine immunisation, Haemophilus influenzae serotype b (Hib) was a
major cause of serious bacterial infections, particularly in young children. In
the United Kingdom, introduction of the Hib conjugate vaccine into the national
childhood immunisation schedule has led to a sustained decline in invasive Hib
disease across all age-groups. Evaluation of the immune response to Hib conjugate
vaccines involves measurement of serum IgG antibodies against the capsular
polyribosyl-ribitol-phosphate (PRP) polysaccharide by enzyme-linked immunosorbent
assay (ELISA), with accepted short-term and long-term protective thresholds of
>=0.15MUg/mL and >=1.0MUg/mL, respectively. These levels were derived by passive
immunisation or immunisation with pure polysaccharide, and their relevance for
protection following immunisation with conjugate vaccines remains unclear. This
study aimed to modify and optimise a serum bactericidal antibody (SBA) assay to
evaluate the functional activity of Hib antibodies generated following Hib
conjugate vaccination. Validation of the Hib SBA assay was deemed acceptable for
all assay parameters tested. A strong correlation between anti-PRP IgG
concentrations and SBA titres was observed in vaccinated adults (r=0.81), as well
as infants after primary immunisation at 2, 3, and 4 months (r=0.635) and after
the 12-month booster (r=0.746). The assay identified some children with high anti
PRP IgG but low SBA activity and vice versa. The predictive protective SBA titre
corresponding to a post-booster anti-PRP IgG of 1.0MUg/mL was 8. Thus, the
optimised Hib SBA assay was specific and reproducible and correlated with anti
PRP IgG. Such assays may have a role in evaluating immune responses to conjugate
vaccines in addition to measuring capsular antibodies.
PMID- 25138291
TI - Development of a BCG challenge model for the testing of vaccine candidates
against tuberculosis in cattle.
AB - Vaccination is being considered as part of a sustainable strategy for the control
of bovine tuberculosis (BTB) in the UK. The live attenuated Mycobacterium bovis
bacillus Calmette-Guerin (BCG) has been used experimentally to vaccinate cattle
against BTB. However, BCG confers partial protection against BTB and therefore,
there is a need to develop improved vaccines. BTB vaccine efficacy experiments
require the use of biosafety level 3 facilities which are expensive to maintain,
generally oversubscribed and represent a bottle neck for the testing of vaccine
candidates. One indicator of the induction of protective responses would be the
ability of the host's immune response to control/kill mycobacteria. In this work
we have evaluated an intranodal BCG challenge for the selection of vaccine
candidates at biosafety level 2 which are capable of inducing mycobactericidal
responses. To our knowledge, this is the first such report. Whilst BCG only
confers partial protection, it is still the standard against which other vaccines
are judged. Therefore we tested the BCG intranodal challenge in BCG (Danish
strain) vaccinated cattle and showed that vaccinated cattle had lower BCG cfu
counts than naive cattle at 14 and 21 days after intranodal challenge with BCG
(Tokyo strain). This model could help prioritize competing TB vaccine candidates
and exploration of primary and secondary immune responses to mycobacteria.
PMID- 25138295
TI - Resumption of work after acute coronary syndrome or coronary artery bypass
surgery.
PMID- 25138292
TI - Rethinking cumulative exposure in epidemiology, again.
AB - The use of cumulative exposure, the product of intensity and duration, has
enjoyed great popularity in epidemiology of chronic diseases despite numerous
known caveats in its interpretation. We briefly review the history of use of
cumulative exposure in epidemiology and propose an alternative method for
relating time-integrated exposures to health risks. We argue, as others before us
have, that cumulative exposure metrics obscures the interplay of exposure
intensity and duration. We propose to use a computationally simple alternative in
which duration and intensity of exposure are modelled as a main effect and their
interaction, cumulative exposure, only be added if there is evidence of deviation
from this additive model. We also consider the Lubin-Caporaso model of interplay
of exposure intensity and duration. The impact of measurement error in intensity
on model selection was also examined. The value of this conceptualization is
demonstrated using a simulation study and further illustrated in the context of
respiratory health and occupational exposure to latex dust. We demonstrate why
cumulative exposure has been so popular because the cumulative exposure metric
per se gives a robust answer to the existence of an association, regardless of
the underlying true mechanism of disease. Treating cumulative exposure as the
interaction of main effects of exposure duration and intensity enables
epidemiologists to derive more information about mechanism of disease then
fitting cumulative exposure metric by itself, and without the need to collect
additional data. We propose that the practice of fitting duration, intensity and
cumulative exposure separately to epidemiologic data should lead to
conceptualization of cumulative exposure as interaction of main effects of
duration and intensity of exposure.
PMID- 25138293
TI - Impact of ambient fine particulate matter carbon measurement methods on observed
associations with acute cardiorespiratory morbidity.
AB - Elemental carbon (EC) and organic carbon (OC) represent a substantial portion of
particulate matter <2.5 MUm in diameter (PM2.5), and have been associated with
adverse health effects. EC and OC are commonly measured using the National
Institute of Occupational Safety and Health (NIOSH) method or the Interagency
Monitoring of Protected Visual Environments (IMPROVE) method. Measurement method
differences could have an impact on observed epidemiologic associations. Daily
speciated PM2.5 data were obtained from the St Louis-Midwest Supersite, and St
Louis emergency department (ED) visit data were obtained from the Missouri
Hospital Association for the period June 2001 to April 2003. We assessed acute
associations between cardiorespiratory ED visits and EC and OC from NIOSH and
IMPROVE methods using Poisson generalized linear models controlling for temporal
trends and meteorology. Associations were generally similar for EC and OC from
the different measurement methods. The most notable difference between methods
was observed for congestive heart failure and EC (for example, warm season rate
ratios (95% confidence intervals) per interquartile range change in EC
concentration were: NIOSH=1.06 (0.99-1.13), IMPROVE=1.01 (0.96-1.07)). Overall,
carbon measurement method had little impact on acute associations between EC, OC,
and ED visits. Some specific differences were observed, however, which may be
related to particle composition.
PMID- 25138294
TI - Cow allergen (Bos d2) and endotoxin concentrations are higher in the settled dust
of homes proximate to industrial-scale dairy operations.
AB - Airborne contaminants produced by industrial agricultural facilities contain
chemical and biological compounds that can impact the health of residents living
in close proximity. Settled dust can be a reservoir for these contaminants and
can influence long-term exposures. In this study, we sampled the indoor- and
outdoor-settled dust from 40 homes that varied in proximity to industrial-scale
dairies (ISD; industrial-scale dairy, a term used in this paper to describe a
large dairy farm and adjacent waste sprayfields, concentrated animal feeding
operation or animal feeding operation, that uses industrial processes) in the
Yakima Valley, Washington. We analyzed settled dust samples for cow allergen (Bos
d2, a cow allergen associated with dander, hair, sweat and urine, it is a member
of the lipocalin family of allergens associated with mammals), mouse allergen
(Mus m1; major mouse allergen, a mouse urinary allergen, in the lipocalin
family), dust mite allergens (Der p1 (Dermatophagoides pteronissinus 1) and Der
f1 (Dermatophagoides farinae 1)), and endotoxin (a component of the cell walls of
gram negative bacteria, lipopolysaccharide, which can be found in air and dust
and can produce a strong inflammatory response). A concentration gradient was
observed for Bos d2 and endotoxin measured in outdoor-settled dust samples based
on proximity to ISD. Indoor-settled dust concentrations of Bos d2 and endotoxin
were also highest in proximal homes. While the associated health effects of
exposure to cow allergen in settled dust is unknown, endotoxin at concentrations
observed in these proximal homes (100 EU/mg) has been associated with increased
negative respiratory health effects. These findings document that biological
contaminants emitted from ISDs are elevated in indoor- and outdoor-settled dust
samples at homes close to these facilities and extend to as much as three miles
(4.8 km) away.
PMID- 25138296
TI - Primary central nervous system lymphoma in the elderly.
PMID- 25138297
TI - Prognosis factors in Japanese elderly patients with primary central nervous
system lymphoma treated with a nonradiation, intermediate-dose methotrexate
containing regimen.
AB - BACKGROUND: Nearly half of all patients with primary central nervous system
lymphoma (PCNSL) are known to be aged over 60 years. However, clinical factors
affecting treatment outcomes in elderly patients are understudied. METHODS: We
analyzed 38 patients with PCNSL older than 60 years. All patients were treated
with a nonradiation, intermediate-dose methotrexate-containing regimen between
March 2005 and May 2013 at the University of Tsukuba Hospital. RESULTS: The 3
year overall survival and progression-free survival rates were 56.2% (95%
confidence interval (CI) 36.2-76.2%) and 29.8% (95% CI 9-50.6%), respectively,
with a median follow-up of 36.5 months. We found that an age > 75 years, a
Karnofsky performance score < 70, altered mentation, and a creatinine clearance
(CrCl) > 90 ml/min were significant (p < 0.05) factors associated with a worse
survival, by univariate analysis. Multivariate analysis revealed that CrCl (p <
0.05; hazard ratio (HR) = 3.39; 95% CI 1.08-10.68) and altered mentation (p <
0.05; HR = 6.27; 95%CI 1.37-28.83) were independent significant association
factors. The most frequent adverse event was myelosuppression, with grade 3-4
hematologic toxicities in 28 patients. No delayed neurotoxicities were observed.
CONCLUSION: More intensive therapy may be introduced in selected patients with
poor prognosis factors to improve outcomes.
PMID- 25138298
TI - Distress in cancer patients and their caregivers and association with the
caregivers' perception of dyadic communication.
AB - BACKGROUND: Discrepancies within cancer-affected couples can disrupt security
within the dyadic relationship during cancer treatment. This study investigated
the patients' and caregivers' distress and associations between the caregivers'
perception of the patients' degree of open communication and their distress.
PARTICIPANTS AND METHODS: In a cross-sectional survey, 189 pairs of cancer
patients (31% gastrointestinal, 34% lung, 35% urological cancers) and their
partners were assessed for distress (QSC-R10), depression and anxiety (PHQ-2/GAD
2). The caregivers also reported their perception of the patients' degree of
disclosure regarding cancer-relevant topics (CCAT-F Disclosure subscale),
caregiver strain (CSI), and unmet needs (SCNS-P&C). Prevalences of clinically
significant distress were calculated. Associations were calculated between the
caregivers' and the patients' ratings and between the caregivers' distress and
their perception of the patients' degree of disclosure. RESULTS: 33% of the
caregivers and 25% of the patients exhibited significant anxiety, with a tendency
towards a higher frequency in the caregivers (p = 0.10). The prevalence of
depression was lower but equally high in caregivers and patients. The caregivers'
perceived non-disclosure by the patients was primarily associated with their
anxiety (r = 0.31), disease-specific distress (r = 0.32), and
psychological/emotional needs (r = 0.35). CONCLUSION: The identification of
caregivers reporting problems in communicating with patients should be pursued in
clinical practice as this might indicate that caregivers are particularly
burdened.
PMID- 25138299
TI - Thymic epithelial tumors: analysis of prognostic factors with emphasis on the
role of adjuvant radiation therapy.
AB - BACKGROUND: The prognostic impacts of histopathological classification, Masaoka
staging system, extent of surgery, and adjuvant treatment approaches in thymic
epithelial tumors (TETs) were investigated. MATERIAL AND METHODS: Records of 22
patients were retrospectively reviewed. Total thymectomy was performed on 5
patients and thymectomy on 17. Complete resection was achieved for 14 patients.
Radiation therapy (RT) was considered for all patients with stage III or IV
disease and all patients undergoing incomplete resections. RESULTS: Local control
had been achieved in all patients and all were alive with no evidence of disease
(ANED) at 0.2-7.8 years (median, 2.3 years). Of 4 patients with stage II disease,
2 (favorable group) had undergone complete resections and 2 (intermediate group)
had undergone incomplete resections. Those undergoing incomplete resections had
received RT. Of these 4 patients, all were ANED. All 4 patients with Masaoka
stage III disease that were involved in the study had undergone incomplete
resections and had received RT. Also, these patients were ANED. CONCLUSIONS:
Patients with TETs undergoing less than complete resections might be referred for
RT in the postoperative setting, while the role of RT in patients undergoing
complete resections remains unclear.
PMID- 25138300
TI - Staging of primary breast cancer is not indicated in asymptomatic patients with
early tumor stages.
AB - BACKGROUND: The routinely practiced staging for distant metastasis in patients
with primary breast cancer has been increasingly questioned. PATIENTS AND
METHODS: Data from 742 patients with breast cancer who had completed staging
(chest x-ray, liver ultrasound, and bone scan) were retrospectively analyzed.
Present findings were transferred to a dataset of a voluntarily monitored
benchmarking project by the West German Breast Center that included patient data
of 179 breast cancer centers. RESULTS: Routine staging examinations revealed in
1.2% (n = 9) distant metastasis and in 38.8% (n = 288) suspicious results. In
total, 15 patients (2%) had distant metastases confirmed by additional
diagnostics. The existence of distant metastases correlated with tumor size,
nodal state, and lymphatic vessel spread. Tumor size and nodal state were
independent predictors for disseminated disease. The risk of exhibiting distant
metastases was 0.77% for patients with tumor stage pT1 pN1. Based on these
findings, in 159,310 patients 41,728 chest x-rays, 43,950 liver ultrasounds, and
39,037 bone scans could have been avoided. CONCLUSION: Asymptomatic patients with
tumor stages <= pT1 pN1 do not benefit from staging of primary breast cancer.
Suspending staging examinations for these patients could reduce cost without
restricting oncologic safety.
PMID- 25138301
TI - Meta-analyses of the effect of CYP1A1 and CYP2D6 polymorphisms on the risk of
head and neck squamous cell carcinoma.
AB - BACKGROUND: CYP1A1 and CYP2D6 are important genes encoding enzymes involved in
the metabolism of toxic chemicals and carcinogens. However, inconclusive results
for the association between CYP1A1 and CYP2D6 polymorphisms and the risk of head
and neck squamous cell carcinoma (HNSCC) have been reported. We conducted a meta
analysis to evaluate the association of CYP1A1 and CYP2D6 polymorphisms with the
risk of HNSCC. METHODS: A database search yielded 19 relevant studies. 3
polymorphisms were included in the meta-analysis: CYP1A1, CYP2D6*4 and CYP2D6*10.
Random or fixed effect models were used in the analysis. RESULTS: The CYP1A1
polymorphism was associated with HNSCC (for m1m1 vs. m1m2: odds ratio (OR) =
1.26, 95% confidence interval (CI) = 1.030-1.542, pheterogeneity = 0.025; for the
recessive model: OR = 1.316, 95% CI = 1.065-1.625, pheterogeneity = 0.001). The
analysis showed evidence for association between the CYP2D6*4 polymorphism and
HNSCC in Asian populations; however, negative results were also observed in other
models. A significant association was also observed between CYP2D6*10
polymorphism and HNSCC risk. CONCLUSIONS: The current study demonstrates that the
CYP1A1 and CYP2D6 polymorphisms are associated with susceptibility to both
development and progression of HNSCC.
PMID- 25138302
TI - CyberKnife Treatment for Kaposiform Hemangioendothelioma of the Ilium in an
adult: case report and review of the literature.
AB - BACKGROUND: Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm
that mainly affects infants. KHE rarely develops in adolescents and adults. These
tumors tend to be locally invasive, but are not known to produce distant
metastases. Numerous treatment modalities are available for KHE, but the optimal
therapy is unknown. CASE REPORT: A 51-year-old woman was diagnosed with KHE of
the ilium in September 2005. The lesion recurred within 5 years of local
excision, and was subsequently treated with CyberKnife. Within 1 month of
CyberKnife therapy, pain intensity was significantly reduced and the patient's
quality of life was significantly improved. Since January 2011, she has remained
pain-free and has had no signs of recurrence or metastasis for more than 2 years
following CyberKnife therapy. CONCLUSION: We report the first CyberKnife
treatment of an adult with KHE of the bone without accompanying cutaneous changes
and Kasabach-Merritt syndrome. CyberKnife treatment could be a useful temporizing
measure for bone KHE.
PMID- 25138303
TI - DNA repair gene--XRCC1 in relation to genome instability and role in colorectal
carcinogenesis.
AB - Colorectal carcinogenesis is a multifactorial and multi-gene process, involving 3
major genetic instability pathways: chromosomal instability, microsatellite
instability and CpG island methylator phenotype. Inefficient DNA repair is one of
the causes of genetic instability leading to tumorigenesis. Defects in DNA repair
genes are associated with cancer development. The XRCC1 gene is an important DNA
repair genes and forms the component of several different damage recovery
pathways, including base excision repair and single-strand breaks repair - the
processes frequently involved in cancer transformation. In this review we have
shed light on the structure and functioning of the XRCC1 gene and its protein,
and the role played by XRCC1 in colorectal carcinogenesis.
PMID- 25138304
TI - PAPST1 regulates sulfation of heparan sulfate proteoglycans in epithelial MDCK II
cells.
AB - Proteoglycan (PG) sulfation depends on activated nucleotide sulfate, 3'
phosphoadenosine-5'-phosphosulfate (PAPS). Transporters in the Golgi membrane
translocate PAPS from the cytoplasm into the organelle lumen where PG sulfation
occurs. Silencing of PAPS transporter (PAPST) 1 in epithelial MDCK cells reduced
PAPS uptake into Golgi vesicles. Surprisingly, at the same time sulfation of
heparan sulfate (HS) was stimulated. The effect was pathway specific in polarized
epithelial cells. Basolaterally secreted proteoglycans (PGs) displayed an altered
HS sulfation pattern and increased growth factor binding capacity. In contrast,
the sulfation pattern of apically secreted PGs was unchanged while the secretion
was reduced. Regulation of PAPST1 allows epithelial cells to prioritize between
PG sulfation in the apical and basolateral secretory routes at the level of the
Golgi apparatus. This provides sulfation patterns that ensure PG functions at the
extracellular level, such as growth factor binding.
PMID- 25138306
TI - Theoretical study of enzymatic catalysis explains why the trapped covalent
intermediate in the E303C mutant of glycosyltransferase GTB was not detected in
the wild-type enzyme.
AB - Hybrid quantum mechanics/molecular mechanics calculations were used to study the
catalytic mechanism of the retaining human alpha-(1,3)-galactosyltransferase
(GTBWT) and its E303C mutant (GTBE303C). Both backside (via covalent glycosyl
enzyme intermediate, CGEI) and frontside SNi-like mechanisms (via oxocarbenium
ion intermediate, OCII) were investigated. The calculations suggest that both
mechanisms are feasible in the enzymatic catalysis. The nucleophilic attack of
the acceptor substrate to the anomeric carbon of OCII is the rate-determining
step with an overall reaction barrier (DeltaE(?) = 19.5 kcal mol(-1)) in
agreement with an experimental rate constant (kcat = 5.1 s(-1)). A calculated
alpha-secondary kinetic isotope effect (alpha-KIE) of 1.27 (GTBWT) and 1.26
(GTBE303C) predicts dissociative character of the transition state in agreement
with experimentally measured alpha-KIE of other retaining glycosyltransferases.
Remarkably, stable CGEI in GTBE303C compared with its counterpart in GTBWT may
explain why the CGEI has been detected by mass spectrometry only in GTBE303C (
Soya N, Fang Y, Palcic MM, Klassen JS. 2011. Trapping and characterization of
covalent intermediates of mutant retaining glycosyltransferases. Glycobiology,
21: 547-552).
PMID- 25138305
TI - Galectin-3 in angiogenesis and metastasis.
AB - Galectin-3 is a member of the family of beta-galactoside-binding lectins
characterized by evolutionarily conserved sequences defined by structural
similarities in their carbohydrate-recognition domains. Galectin-3 is a unique,
chimeric protein consisting of three distinct structural motifs: (i) a short NH2
terminal domain containing a serine phosphorylation site; (ii) a repetitive
proline-rich collagen-alpha-like sequence cleavable by matrix metalloproteases;
and (iii) a globular COOH-terminal domain containing a carbohydrate-binding motif
and an NWGR anti-death motif. It is ubiquitously expressed and has diverse
biological functions depending on its subcellular localization. Galectin-3 is
mainly found in the cytoplasm, also seen in the nucleus and can be secreted by
non-classical, secretory pathways. In general, secreted galectin-3 mediates cell
migration, cell adhesion and cell-cell interactions through the binding with high
affinity to galactose-containing glycoproteins on the cell surface. Cytoplasmic
galectin-3 exhibits anti-apoptotic activity and regulates several signal
transduction pathways, whereas nuclear galectin-3 has been associated with pre
mRNA splicing and gene expression. Its unique chimeric structure enables it to
interact with a plethora of ligands and modulate diverse functions such as cell
growth, adhesion, migration, invasion, angiogenesis, immune function, apoptosis
and endocytosis emphasizing its significance in the process of tumor progression.
In this review, we have focused on the role of galectin-3 in tumor metastasis
with special emphasis on angiogenesis.
PMID- 25138307
TI - Residents' and preceptors' perceptions of the use of the iPad for clinical
teaching in a family medicine residency program.
AB - BACKGROUND: As Family Medicine programs across Canada are transitioning into a
competency-based curriculum, medical students and clinical teachers are
increasingly incorporating tablet computers in their work and educational
activities. The purpose of this pilot study was to identify how preceptors and
residents use tablet computers to implement and adopt a new family medicine
curriculum and to evaluate how they access applications (apps) through their
tablet in an effort to support and enhance effective teaching and learning.
METHODS: Residents and preceptors (n = 25) from the Family Medicine program
working at the Pembroke Regional Hospital in Ontario, Canada, were given iPads
and training on how to use the device in clinical teaching and learning
activities and how to access the online curriculum. Data regarding the use and
perceived contribution of the iPads were collected through surveys and focus
groups. This mixed methods research used analysis of survey responses to support
the selection of questions for focus groups. RESULTS: Reported results were
categorized into: curriculum and assessment; ease of use; portability; apps and
resources; and perceptions about the use of the iPad in teaching/learning
setting. Most participants agreed on the importance of accessing curriculum
resources through the iPad but recognized that these required enhancements to
facilitate use. The iPad was considered to be more useful for activities
involving output of information than for input. Participants' responses regarding
the ease of use of mobile technology were heterogeneous due to the diversity of
computer proficiency across users. Residents had a slightly more favorable
opinion regarding the iPad's contribution to teaching/learning compared to
preceptors. CONCLUSIONS: iPad's interface should be fully enhanced to allow easy
access to online curriculum and its built-in resources. The differences in
computer proficiency level among users should be reduced by sharing knowledge
through workshops led by more skillful iPad users. To facilitate collection of
information through the iPad, the design of electronic data-input forms should
consider the participants' reported negative perceptions towards typing data
through mobile devices. Technology deployment projects should gather sufficient
evidence from pilot studies in order to guide efforts to adapt resources and
infrastructure to relevant needs of Family Medicine teachers and learners.
PMID- 25138308
TI - Diglycerol-based polyesters: melt polymerization with hydrophobic anhydrides.
AB - The melt polymerization of diglycerol with bicyclic anhydride monomers derived
from a naturally occurring monoterpene provides an avenue for polyesters with a
high degree of sustainability. The hydrophobic anhydrides are synthesized at
ambient temperature via a solvent-free Diels-Alder reaction of alpha-phellandrene
with maleic anhydride. Subsequent melt polymerizations with tetra-functional
diglycerol are effective under a range of [diglycerol]/[anhydride] ratios. The
hydrophobicity of alpha-phellandrene directly impacts the swelling behavior of
the resulting polyesters. The low E factors (<2), large amount of bio-based
content (>75%), ambient temperature monomer synthesis, and polymer degradability
represent key factors in the design of these sustainable polyesters.
PMID- 25138309
TI - Prevalence of methicillin-resistant Staphylococcus aureus : effect of different
criteria for elimination of duplicates.
AB - BACKGROUND: The purpose of this study is to compare the effect of different
systems for eliminating duplicates in order to optimize the calculation of the
prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection.
METHODS: We compare the Clinical and Laboratory Standards Institute (CLSI)
criterion, time criteria and the criterion recommended by the European
Antimicrobial Surveillance System (EARSS). RESULTS: Multiple isolates of MRSA are
frequently recovered from successive cultures from the same patient (the average
isolation rate of MRSA is 2.72), which demonstrates the importance of eliminating
duplicates. When CLSI criterion data are compared to those obtained using other
criteria, a significant increase in the number of S. aureus isolates was found
applying time criteria (up to 36%) or the EARSS criterion (13%). There is also an
increase in the methicillin resistance rate (between 3.31 and 3.96%; p < 0.01).
CONCLUSIONS: We believe that the EARSS method, with the proper quality controls
and latest software tools available, is the best for determining the true
situation of MRSA.
PMID- 25138310
TI - Circulating mRNA for the PLAC1 gene as a second trimester marker (14-18 weeks'
gestation) in the screening for late preeclampsia.
AB - OBJECTIVE: To develop a model for prediction of late preeclampsia (PE; which
develops at or after 34 weeks' gestation) based on maternal history and
characteristics, mean arterial pressure (MAP), and circulating levels of mRNA for
the placenta-specific 1 (PLAC1) gene in maternal plasma at 14-18 weeks'
gestation. METHOD: This was a screening study of singleton pregnancies at 14-18
weeks' gestation including 43 women that subsequently developed PE and 200 that
were unaffected by PE. A Gaussian model was fitted to the log distribution of the
multiple of the median (log MoM) PLAC1 mRNA in the PE group and in the unaffected
group. Likelihood ratios for log MoM of circulating levels of mRNA for the PLAC1
gene were used to combine the a priori risk from maternal characteristics with
MAP to produce patient-specific risks for each case. RESULTS: Screening by
maternal characteristics (including BMI, woman's mother's history of PE, previous
PE, and parity) (a priori risk) and MAP detected 46.8% of all cases of late PE at
a fixed false-positive rate (FPR) of 10%. The addition of PLAC1 yielded a
detection rate (DR) of 62.8% at the same level of FPR. PLAC1 alone yielded a DR
of 30.2%. CONCLUSION: In late PE, molecular markers can be used to improve the DR
of screening and can be a valid option for the biochemical approach.
PMID- 25138313
TI - Super-responders to cardiac resynchronization therapy remain at risk for
ventricular arrhythmias and benefit from defibrillator treatment.
AB - AIMS: Mortality and ventricular arrhythmias are reduced in patients responding to
cardiac resynchronization therapy (CRT). This response is accompanied by
improvement in LVEF, and some patients even outgrow original eligibility criteria
for implantable cardioverter-defibrillator (ICD) implantation. It is however
unclear if these patients still benefit from ICD treatment. The current study
aimed to evaluate if the incidence of ICD therapy is related to the extent of CRT
response. METHODS AND RESULTS: All patients who underwent primary prevention CRT
defibrillator implantation were included. They were divided into subgroups
according to the reduction in LV end-systolic volume (LVESV) 6 months after
implantation. Pre-defined subgroups were: negative responders (increased LVESV),
non-responders (decreased LVESV 0-14%), responders (decreased LVESV 15-29%), and
super-responders (decreased LVESV >=30%). During a median follow-up of 57 months
(25th-75th percentile 39-84), 512 patients were studied [101 (20%) negative
responders, 101 (20%) non-responders, 149 (29%) responders, and 161 (31%) super
responders]. In the first year of follow-up super-responders received
significantly less appropriate ICD therapy (3% vs. 12%; P < 0.001). The 5-year
cumulative incidence of appropriate ICD therapy was 31% [95% confidence interval
(CI) 19-43] in negative responders, 39% (95% CI 25-53) in non-responders, 34%
(95% CI 25-43) in responders, and 27% (95% CI 18-35) in super-responders,
respectively (p = 0.13). CONCLUSIONS: The extent of CRT response was associated
with a parallel reduction of appropriate device therapy during the first year of
follow-up. Thereafter, no association was observed. Furthermore, 23% of super
responders were treated for potentially life-threatening arrhythmias and benefit
from ICD treatment.
PMID- 25138312
TI - Personal and psychosocial predictors of doping use in physical activity settings:
a meta-analysis.
AB - BACKGROUND: There is a growing body of empirical evidence on demographic and
psychosocial predictors of doping intentions and behaviors utilizing a variety of
variables and conceptual models. However, to date there has been no attempt to
quantitatively synthesize the available evidence and identify the strongest
predictors of doping. OBJECTIVES: Using meta-analysis, we aimed to (i) determine
effect sizes of psychological (e.g. attitudes) and social-contextual factors
(e.g. social norms), and demographic (e.g. sex and age) variables on doping
intentions and use; (ii) examine variables that moderate such effect sizes; and
(iii) test a path analysis model, using the meta-analyzed effect sizes, based on
variables from the theory of planned behavior (TPB). DATA SOURCES: Articles were
identified from online databases, by contacting experts in the field, and
searching the World Anti-Doping Agency website. STUDY ELIGIBILITY CRITERIA AND
PARTICIPANTS: Studies that measured doping behaviors and/or doping intentions,
and at least one other demographic, psychological, or social-contextual variable
were included. We identified 63 independent datasets. STUDY APPRAISAL AND
SYNTHESIS METHOD: Study information was extracted by using predefined data fields
and taking into account study quality indicators. A random effects meta-analysis
was carried out, correcting for sampling and measurement error, and identifying
moderator variables. Path analysis was conducted on a subset of studies that
utilized the TPB. RESULTS: Use of legal supplements, perceived social norms, and
positive attitudes towards doping were the strongest positive correlates of
doping intentions and behaviors. In contrast, morality and self-efficacy to
refrain from doping had the strongest negative association with doping intentions
and behaviors. Furthermore, path analysis suggested that attitudes, perceived
norms, and self-efficacy to refrain from doping predicted intentions to dope and,
indirectly, doping behaviors. LIMITATIONS: Various meta-analyzed effect sizes
were based on a small number of studies, which were correlational in nature. This
is a limitation of the extant literature. CONCLUSIONS: This review identifies a
number of important correlates of doping intention and behavior, many of which
were measured via self-reports and were drawn from an extended TPB framework.
Future research might benefit from embracing other conceptual models of doping
behavior and adopting experimental methodologies that will test some of the
identified correlates in an effort to develop targeted anti-doping policies and
programs.
PMID- 25138311
TI - A systematic review and meta-analysis of concussion in rugby union.
AB - BACKGROUND: Rugby Union, a popular full-contact sport played throughout the
world, has one of the highest rates of concussion of all full-contact sports.
OBJECTIVE: The aim of the current review was to systematically evaluate the
available evidence on concussion in Rugby Union and to conduct a meta-analysis of
findings regarding the incidence of concussion. METHODS: Articles were retrieved
via a number of online databases. The current review examined all articles
published in English up to May 2014 pertaining to concussion in Rugby Union
players. The key search terms included 'Rugby Union', 'rugby', 'union', and
'football', in combination with the injury terms 'athletic injuries',
'concussion', 'sports concussion', 'sports-related concussion', 'brain
concussion', 'brain injury', 'brain injuries', 'mild traumatic brain injury',
'mTBI', 'traumatic brain injury', 'TBI', 'craniocerebral trauma', 'head injury',
and 'brain damage'. RESULTS: The final search outcome following the eligibility
screening process resulted in the inclusion of 96 articles for this review. The
meta-analysis included a total of 37 studies. The results of the meta-analysis
revealed an overall incidence of match-play concussion in men's rugby-15s of 4.73
per 1,000 player match hours. The incidence of concussion during training was
0.07 per 1,000 practice hours. The incidence of concussion in women's rugby-15s
was 0.55 per 1,000 player match hours. In men's rugby-7s match-play, concussion
incidence was 3.01 per 1,000 player match hours. The incidence of concussion
varied considerably between levels of play, with elite level play recording a
rate of 0.40 concussions per 1,000 player match hours, schoolboy level 0.62
concussions per 1,000 player match hours, and the community or sub-elite level
recording a rate of 2.08 concussions per 1,000 player match hours. The incidence
of concussion in men's rugby-15s as a function of playing position (forwards vs.
backs) was 4.02 and 4.85 concussions per 1,000 player match hours, respectively.
CONCLUSIONS: Concussion is a common injury sustained and reported in match play
and to a lesser extent during practice by Rugby Union players. Based on the
available published data, there appears to be a variation in risk of concussion
across level of play, with the sub-elite level having the greatest incidence of
injury. Future research focused on studying the acute consequences and best
management strategies in current players, and the potential longer term outcomes
of concussion in retired players, is needed. A focus on the areas of prevention,
injury identification, and medical management, and risk for long-term outcomes
will be of benefit to current athletes.
PMID- 25138314
TI - Physiological and biochemical characterization of Azospirillum brasilense strains
commonly used as plant growth-promoting rhizobacteria.
AB - Azospirillum is a plant growth-promoting rhizobacteria (PGPR) genus vastly
studied and utilized as agriculture inoculants. Isolation of new strains under
different environmental conditions allows the access to the genetic diversity and
improves the success of inoculation procedures. Historically, the isolation of
this genus has been performed by the use of some traditional culture media. In
this work we characterized the physiology and biochemistry of five different A.
brasilense strains, commonly used as cereal inoculants. The aim of this work is
to contribute to pose into revision some concepts concerning the most used
protocols to isolate and characterize this bacterium. We characterized their
growth in different traditional and non-traditional culture media, evaluated some
PGPR mechanisms and characterized their profiles of fatty acid methyl esters and
carbon-source utilization. This work shows, for the first time, differences in
both profiles, and ACC deaminase activity of A. brasilense strains. Also, we show
unexpected results obtained in some of the evaluated culture media. Results
obtained here and an exhaustive knowledge revision revealed that it is not
appropriate to conclude about bacterial species without analyzing several
strains. Also, it is necessary to continue developing studies and laboratory
techniques to improve the isolation and characterization protocols.
PMID- 25138315
TI - Steric self-assembly of laterally confined organic semiconductor molecule
analogues.
AB - Self-assembly of planar molecules can be a critical route to control morphology
in organic optoelectronic systems. In this study, Monte Carlo simulations were
performed with polygonal disc analogues to planar semiconducting molecules under
confinement. By examining statistically the molecular density and configurations
of such analogues, we have observed that the symmetry of the confining medium can
have a greater impact on the final densified particle configurations than the
intramolecular interactions. Using the steric frustration imparted by
confinement, novel self-assembled (partially) ordered phases are available. Our
Monte Carlo simulations suggest new avenues to control ordering and morphology of
planar molecules, which are critical for high-performance organic optoelectronic
devices.
PMID- 25138318
TI - "The beautyful ones are not yet born" might not hold true for much longer:
Njideka Akunyili.
PMID- 25138319
TI - CDC: Ebola risk to US patients is low, but clinicians should be on alert.
PMID- 25138329
TI - A piece of my mind. Beyond conflicts of interest: disclosing medical biases.
PMID- 25138330
TI - Bronchiolitis, deception in research, and clinical decision making.
PMID- 25138331
TI - Newborn screening for severe combined immunodeficiency: progress and challenges.
PMID- 25138332
TI - Effect of oximetry on hospitalization in bronchiolitis: a randomized clinical
trial.
AB - IMPORTANCE: Routine use of pulse oximetry has been associated with changes in
bronchiolitis management and may have lowered the hospitalization threshold for
patients with bronchiolitis. OBJECTIVE: To examine if infants with bronchiolitis
whose displayed oximetry measurements have been artificially elevated 3
percentage points above true values experience hospitalization rates at least 15%
lower compared with infants with true values displayed. DESIGN, SETTING, AND
PARTICIPANTS: Randomized, double-blind, parallel-group trial conducted from 2008
to 2013 in a tertiary-care pediatric emergency department in Toronto, Ontario,
Canada. Participants were 213 otherwise healthy infants aged 4 weeks to 12 months
with mild to moderate bronchiolitis and true oxygen saturations of 88% or higher.
INTERVENTIONS: Pulse oximetry measurements with true saturation values displayed
or with altered saturation values displayed that have been increased 3 percentage
points above true values. MAIN OUTCOMES AND MEASURES: The primary outcome was
hospitalization within 72 hours, defined as inpatient admission within this
interval or active hospital care for greater than 6 hours. Secondary outcomes
included the use of supplemental oxygen in the emergency department, level of
physician agreement with discharge from the emergency department, length of
emergency department stay, and unscheduled visits for bronchiolitis within 72
hours. RESULTS: Forty-four of 108 patients (41%) in the true oximetry group and
26 of 105 (25%) in the altered oximetry group were hospitalized within 72 hours
(difference, 16% [95% CI for the difference, 3.6% to 28.4%]; P = .005). Using the
emergency department physician as a random effect, the primary treatment effect
remained significant (adjusted odds ratio, 4.0 [95% CI, 1.6 to 10.5]; P = .009).
None of the secondary outcomes were significantly different between the groups.
There were 23 of 108 (21.3%) subsequent unscheduled medical visits for
bronchiolitis in the true oximetry group and 15 of 105 (14.3%) in the altered
oximetry group (difference, 7% [95% CI, -0.3% to 0.2%]; P = .18). CONCLUSIONS AND
RELEVANCE: Among infants presenting to an emergency department with mild to
moderate bronchiolitis, those with an artificially elevated pulse oximetry
reading were less likely to be hospitalized within 72 hours or to receive active
hospital care for more than 6 hours than those with unaltered oximetry readings.
This suggests that oxygen saturation should not be the only factor in the
decision to admit, and its use may need to be reevaluated. TRIAL REGISTRATION:
clinicaltrials.gov Identifier: NCT00673946.
PMID- 25138333
TI - Sustained care intervention and postdischarge smoking cessation among
hospitalized adults: a randomized clinical trial.
AB - IMPORTANCE: Health care systems need effective models to manage chronic diseases
like tobacco dependence across transitions in care. Hospitalizations provide
opportunities for smokers to quit, but research suggests that hospital-delivered
interventions are effective only if treatment continues after discharge.
OBJECTIVE: To determine whether an intervention to sustain tobacco treatment
after hospital discharge increases smoking cessation rates compared with standard
care. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial compared
sustained care (a postdischarge tobacco cessation intervention) with standard
care among 397 hospitalized daily smokers (mean age, 53 years; 48% were males;
81% were non-Hispanic whites) who wanted to quit smoking after discharge and
received a tobacco dependence intervention in the hospital; 92% of eligible
patients and 44% of screened patients enrolled. The study was conducted from
August 2010 through November 2012 at Massachusetts General Hospital.
INTERVENTIONS: Sustained care participants received automated interactive voice
response telephone calls and their choice of free smoking cessation medication
(any type approved by the US Food and Drug Administration) for up to 90 days. The
automated telephone calls promoted cessation, provided medication management, and
triaged smokers for additional counseling. Standard care participants received
recommendations for postdischarge pharmacotherapy and counseling. MAIN OUTCOMES
AND MEASURES: The primary outcome was biochemically confirmed past 7-day tobacco
abstinence at 6-month follow-up after discharge from the hospital; secondary
outcomes included self-reported tobacco abstinence. RESULTS: Smokers randomly
assigned to sustained care (n = 198) used more counseling and more
pharmacotherapy at each follow-up assessment than those assigned to standard care
(n = 199). Biochemically validated 7-day tobacco abstinence at 6 months was
higher with sustained care (26%) than with standard care (15%) (relative risk
[RR], 1.71 [95% CI, 1.14-2.56], P = .009; number needed to treat, 9.4 [95% CI,
5.4-35.5]). Using multiple imputation for missing outcomes, the RR for 7-day
tobacco abstinence was 1.55 (95% CI, 1.03-2.21; P = .04). Sustained care also
resulted in higher self-reported continuous abstinence rates for 6 months after
discharge (27% vs 16% for standard care; RR, 1.70 [95% CI, 1.15-2.51]; P = .007).
CONCLUSIONS AND RELEVANCE: Among hospitalized adult smokers who wanted to quit
smoking, a postdischarge intervention providing automated telephone calls and
free medication resulted in higher rates of smoking cessation at 6 months
compared with a standard recommendation to use counseling and medication after
discharge. These findings, if replicated, suggest an approach to help achieve
sustained smoking cessation after a hospital stay. TRIAL REGISTRATION:
clinicaltrials.gov Identifier: NCT01177176.
PMID- 25138335
TI - Red papules on the tongue of a patient with hemiparesis.
PMID- 25138336
TI - Elevated serum ferritin.
PMID- 25138337
TI - Seroprevalence of herpes simplex virus type 1 and 2 among pregnant women, 1989
2010.
PMID- 25138338
TI - Tadalafil for erectile dysfunction prevention after radiotherapy for prostate
cancer.
PMID- 25138339
TI - Tadalafil for erectile dysfunction prevention after radiotherapy for prostate
cancer--reply.
PMID- 25138334
TI - Newborn screening for severe combined immunodeficiency in 11 screening programs
in the United States.
AB - IMPORTANCE: Newborn screening for severe combined immunodeficiency (SCID) using
assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in
2008, and SCID was added to the national recommended uniform panel for newborn
screened disorders in 2010. Currently 23 states, the District of Columbia, and
the Navajo Nation conduct population-wide newborn screening for SCID. The
incidence of SCID is estimated at 1 in 100,000 births. OBJECTIVES: To present
data from a spectrum of SCID newborn screening programs, establish population
based incidence for SCID and other conditions with T-cell lymphopenia, and
document early institution of effective treatments. DESIGN: Epidemiological and
retrospective observational study. SETTING: Representatives in states conducting
SCID newborn screening were invited to submit their SCID screening algorithms,
test performance data, and deidentified clinical and laboratory information
regarding infants screened and cases with nonnormal results. Infants born from
the start of each participating program from January 2008 through the most recent
evaluable date prior to July 2013 were included. Representatives from 10 states
plus the Navajo Area Indian Health Service contributed data from 3,030,083
newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES: Infants with SCID
and other diagnoses of T-cell lymphopenia were classified. Incidence and, where
possible, etiologies were determined. Interventions and survival were tracked.
RESULTS: Screening detected 52 cases of typical SCID, leaky SCID, and Omenn
syndrome, affecting 1 in 58,000 infants (95% CI, 1/46,000-1/80,000). Survival of
SCID-affected infants through their diagnosis and immune reconstitution was 87%
(45/52), 92% (45/49) for infants who received transplantation, enzyme
replacement, and/or gene therapy. Additional interventions for SCID and non-SCID
T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and
avoidance of live vaccines. Variations in definitions and follow-up practices
influenced the rates of detection of non-SCID T-cell lymphopenia. CONCLUSIONS AND
RELEVANCE: Newborn screening in 11 programs in the United States identified SCID
in 1 in 58,000 infants, with high survival. The usefulness of detection of non
SCID T-cell lymphopenias by the same screening remains to be determined.
PMID- 25138340
TI - Statins and ischemic stroke.
PMID- 25138341
TI - Treatment for opioid use disorder.
PMID- 25138342
TI - Statins and ischemic stroke--reply.
PMID- 25138344
TI - Treatment for opioid use disorder--reply.
PMID- 25138346
TI - Hasty generalizations.
PMID- 25138347
TI - The effect of passively acquired antibodies on Lawsonia intracellularis infection
and immunity in the horse.
AB - REASONS FOR PERFORMING STUDY: Multiple hypotheses into the age-based
susceptibility of animals to Lawsonia intracellularis exist, including the
decline of passively acquired antibodies. OBJECTIVES: To determine whether the
decline in passively acquired antibodies in horses is responsible for the age
predilection of equine proliferative enteropathy (EPE). Additional objectives
included examination of various risk factors for the development of EPE as well
as the determination of naturally occurring attack rates for clinical and
subclinical EPE. STUDY DESIGN: Prospective, multifarm field study. METHODS: A
total of 369 mare and foal pairs from 15 central Kentucky Thoroughbred farms were
used in this study, which took place from January 2012 to February 2013. Serum
samples were collected from mares and foals within 48 h of parturition, and then
monthly from foals to February of their yearling year. Lawsonia intracellularis
specific antibodies were measured using an enzyme-linked immunosorbent assay.
RESULTS: No effect of passively acquired antibodies on the occurrence of
presumptive clinical or subclinical EPE was noted. In total, 5.3% and 6.3% of
seropositive horses developed presumptive clinical or subclinical EPE,
respectively. In multiple logistic regression models, colts were at a
significantly greater risk than fillies of developing presumptive clinical EPE
(odds ratio [OR] 5.468, 95% confidence interval [CI] 1.134-26.362, P = 0.034) or
a combination of either presumptive clinical or subclinical EPE (OR 3.861, 95% CI
1.461-10.206, P = 0.006) while foals that were weaned in September or beyond were
at a lower risk of developing presumptive EPE (OR = 0.281, 95% CI 0.0807-0.981, P
= 0.05). CONCLUSIONS: This is the first study to show that passively acquired
antibodies to L. intracellularis do not have an effect on the occurrence of
clinical or subclinical EPE. A number of novel findings, including identification
of the disease rate among naturally exposed horses, warrant additional work as
they may help to identify potential risk factors for L. intracellularis exposure
and/or the reservoir host(s) of the bacterium.
PMID- 25138348
TI - Controlled release of ziprasidone solid dispersion systems from osmotic pump
tablets with enhanced bioavailability in the fasted state.
AB - OBJECTIVE: The purpose of this work was to develop a controlled release of
ziprasidone with no food effect by the osmotic release strategy. METHODS: The
solution of ziprasidone and poloxamer188 (P188) with different weight ratios was
spray-dried to form solid dispersion of ziprasidone (SD-ZIP). The SD-ZIP was
characterized using scanning electron microscopy (SEM), differential scanning
calorimetry (DSC), X-ray powder diffraction (X-RD) and solubility testing. The SD
ZIP osmotic pump tablets were prepared by wet granulation method. The effect of
formulation variables on the release characteristic was investigated. The SD-ZIP
osmotic pump tablets were administered to fasted and fed beagle dogs and their
pharmacokinetics were compared to commercial formulation Zeldox(r) as a control.
RESULTS: The results of DSC and X-RD indicated that ziprasidone resides in P188
with no crystalline changes. Solubility studies demonstrated that the solubility
of SD-ZIP was substantially improved compared to ziprasidone and physical
mixtures of ziprasidone and P188. The optimized formulation and drug release
profiles of SD-ZIP osmotic pump tablets in different medium were obtained which
showed typical osmotically controlled release and could fitted to zero-order
kinetics with good linear correlation. Pharmacokinetic studies in beagle dogs
showed ziprasidone with prolong actions and no food effect was achieved
simultaneously in SD-ZIP osmotic pump tablet compared with Zeldox(r). CONCLUSION:
The SD-ZIP osmotic pump tablet could be able to enhance the bioavailability in
the fasted state and showed sustained release with prolonged actions.
PMID- 25138349
TI - Preparation and evaluation of SEDDS of simvastatin by in vivo, in vitro and ex
vivo technique.
AB - The objective of this work was to formulate a Self Emulsifying Drug Delivery
System (SEDDS) of simvastatin, a poorly soluble drug and to evaluate by in vivo,
in vitro and ex vivo techniques. Oils and surfactants were screened out depending
upon their solubilizing capacity. Among all of the solvents, Capryol 90 showed
good solubilizing capacity. It dissolved 105 mg/ml of simvastatin. Tween-80 also
showed good solubilizing capacity which was 117 mg/ml. The two excipients were
used to prepare simvastatin SEDDS. Formulations were initially checked for the
color, clarity and sedimentation. The SEDDS formulations were transparent and
clear. Formulation F2 containing 7:3 (m/m) mixture of Capryol 90/Tween-80
produced smallest micro-emulsion with particles size of 0.074 um and drug release
was higher than other formulation (102% within 20 min). Ex vivo study of the
SEDDS formulation was evaluated using guinea pig intestinal sac. Drug diffused
from F2 formulation was significantly higher than pure drug (p < 0.001). In vivo
study of SEDDS was performed in albino mice using plasma cholesterol level as a
pharmacodynamic marker parameter. The test formulation (F2) appeared remarkable
reduction in plasma cholesterol level, after oral administration which showed
that SEDDS may be an effective technique for the oral administration of
simvastatin.
PMID- 25138350
TI - Analysis of curing of a sustained release coating formulation by application of
NIR spectroscopy to monitor changes associated with glyceryl monostearate.
AB - For controlled release, latex or pseudolatex coatings to function as designed, it
must be cured at temperatures at or slightly above the polymer's glass transition
temperature. The focus of this study is to develop an understanding of the curing
process and to develop near infrared spectroscopy as a tool for monitoring
curing. Differential scanning calorimetry studies were used to determine how the
thermal properties of glyceryl monostearate (GMS) and its polymorphic forms
relate to the extent of Eudragit(r) polymer coat curing at different curing
temperatures. The different GMS melting endotherms were used to monitor the
extent of curing and as references for model development. The calculated melting
peak areas for the GMS were plotted versus time and found to be dependent on time
and temperature used for curing. Principal component analysis and parallel factor
analysis were used to investigate the effect of curing on the films and showed
that spectral changes could be could be directly related to the changes
associated with the GMS during curing. Partial least square models developed
could predict the extent of curing and the final state of GMS post curing.
PMID- 25138353
TI - Interactions of Papua New Guinea medicinal plant extracts with antiretroviral
therapy.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: A substantial proportion of the population in
Papua New Guinea (PNG) lives with human immunodeficiency virus (HIV). Treatment
requires lifelong use of antiretroviral therapy (ART). The majority of people in
PNG use traditional medicines (TM) derived from plants for all types of health
promotions. Consequently, there is a concern that herb-drug interactions may
impact the efficacy of ART. Herb-drug, or drug-drug, interactions occur at the
level of metabolism through two major mechanisms: enzyme induction or enzyme
inhibition. In this study, extracts of commonly-used medicinal plants from PNG
were screened for herb-drug interactions related to cytochrome P450s (CYPs).
MATERIALS AND METHODS: Sixty nine methanol extracts of TM plants were screened
for their ability to induce CYPs by human aryl hydrocarbon receptor- (hAhR-) and
human pregnane X receptor- (hPXR-) dependent mechanisms, utilizing a commercially
available cell-based luciferase reporter system. Inhibition of three major CYPs,
CYP1A2, CYP3A4, and CYP2D6, was determined using human liver microsomes and
enzyme-selective model substrates. RESULTS: Almost one third of the TM plant
extracts induced the hAhR-dependent expression of CYP1A2, the hPXR-dependent
expression of CYP3A4, or both. Almost two thirds inhibited CYP1A2, CYP3A4, or
CYP2D6, or combinations thereof. Many plant extracts exhibited both induction and
inhibition properties. CONCLUSIONS: We demonstrated that the potent and selective
ability of extracts from PNG medicinal plants to affect drug metabolizing enzymes
through induction and/or inhibition is a common phenomenon. Use of traditional
medicines concomitantly with ART could dramatically alter the concentrations of
antiretroviral drugs in the body; and their efficacy. PNG healthcare providers
should counsel HIV patients because of this consequence.
PMID- 25138354
TI - Inhibition of the toxic effects of Bothrops asper venom by pinostrobin, a
flavanone isolated from Renealmia alpinia (Rottb.) MAAS.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Renealmia alpinia has been traditionally used to
treat snakebites by indigenous Embera-Katios tribes belonging to the regions of
Antioquia and Choco, Colombia, and it has been shown to inhibit the enzymatic and
biological activities of Bothrops venoms and their purified phospholipase A2
(PLA2) toxins. In addition to its common local usage against snakebites,
Renealmia alpinia is commonly used to treat pain. To evaluate the inhibitory
ability of pinostrobin, the main compound in the dichloromethane extract of
Renealmia alpinia, on the toxic effects of Bothrops asper venom through in vitro
and in vivo models and to evaluate its activity against pain and edema. MATERIALS
AND METHODS: Pinostrobin was isolated from the dichloromethane extract of
Renealmia alpinia leaves. The protective properties of the extract and of
pinostrobin against the indirect hemolytic, coagulant and proteolytic effects of
Bothrops asper venom were evaluated in vitro, and the anti-hemorrhagic and anti
inflammatory activity were evaluated in vivo. RESULTS: Renealmia alpinia extract
significantly inhibited the proteolytic activity and indirect hemolytic activity
of Bothrops asper venom at a venom:extract ratio of 1:20. Moreover, the present
data demonstrate that pinostrobin may mitigate some venom-induced local tissue
damage due to hemorrhagic effects, and the compound is also responsible for the
analgesic and anti-inflammatory activity of the extract from Renealmia alpinia.
This is the first report to describe pinostrobin in the species Renealmia alpinia
and its properties in vitro against Bothrops asper venom. CONCLUSION: Our studies
of the activity of Renealmia alpinia against the venom of Bothrops asper have
confirmed that this species possesses inhibitory effects against Bothrops asper
venom in both in vitro and in vivo models and that these effects may be due to
pinostrobin, supporting the traditional usage of the plant. Additionally,
pinostrobin may be responsible for the anti-hemorrhagic and analgesic activity
(peripheral analgesic activity) of Renealmia alpinia.
PMID- 25138355
TI - Itching in patients with chronic hand eczema: data from the CARPE registry.
AB - BACKGROUND: Itching is a leading symptom of chronic hand eczema (CHE) having a
great impact on patients. The determinants of itching in CHE are unclear.
OBJECTIVE: We performed a cross-sectional analysis investigating factors
associated with the presence and severity of itch in CHE patients from the CARPE
registry. METHODS: We present baseline data on itch in relationship with
sociodemographic factors, severity of CHE, atopy, contact allergy, treatment and
patient- reported outcomes including health-related quality of life (HRQoL).
RESULTS: Of 1,051 patients with CHE, 78.1% reported itching. Significant positive
associations with itching were observed for younger age groups (17-25 and 26-45
years), for moderate, severe and very severe CHE and for small/moderate
impairment in HRQoL. Atopic skin diathesis, hardly being able to realize
treatment recommendations and very or extremely large impairments in HRQoL were
associated with itch severity. CONCLUSION: Taking the identified variables into
account may help identify vulnerable groups most affected by (severe) itch.
PMID- 25138356
TI - FTY720 (fingolimod) modulates the severity of viral-induced encephalomyelitis and
demyelination.
AB - BACKGROUND: FTY720 (fingolimod) is the first oral drug approved by the Food and
Drug Administration for treatment of patients with the relapsing-remitting form
of the human demyelinating disease multiple sclerosis. Evidence suggests that the
therapeutic benefit of FTY720 occurs by preventing the egress of lymphocytes from
lymph nodes thereby inhibiting the infiltration of disease-causing lymphocytes
into the central nervous system (CNS). We hypothesized that FTY720 treatment
would affect lymphocyte migration to the CNS and influence disease severity in a
mouse model of viral-induced neurologic disease. METHODS: Mice were infected
intracranially with the neurotropic JHM strain of mouse hepatitis virus. Infected
animals were treated with increasing doses (1, 3 and 10 mg/kg) of FTY720 and
morbidity and mortality recorded. Infiltration of inflammatory virus-specific T
cells (tetramer staining) into the CNS of FTY720-treated mice was determined
using flow cytometry. The effects of FTY720 treatment on virus-specific T cell
proliferation, cytokine production and cytolytic activity were also determined.
The severity of neuroinflammation and demyelination in FTY720-treated mice was
examined by flow cytometry and histopathologically, respectively, in the spinal
cords of the mice. RESULTS: Administration of FTY720 to JHMV-infected mice
resulted in increased clinical disease severity and mortality. These results
correlated with impaired ability to control viral replication (P < 0.05) within
the CNS at days 7 and 14 post-infection, which was associated with diminished
accumulation of virus-specific CD4+ and CD8+ T cells (P < 0.05) into the CNS.
Reduced neuroinflammation in FTY720-treated mice correlated with increased
retention of T lymphocytes within draining cervical lymph nodes (P < 0.05).
Treatment with FTY720 did not affect virus-specific T cell proliferation,
expression of IFN-gamma, TNF-alpha or cytolytic activity. FTY720-treated mice
exhibited a reduction in the severity of demyelination associated with dampened
neuroinflammation. CONCLUSION: These findings indicate that FTY720 mutes
effective anti-viral immune responses through impacting migration and
accumulation of virus-specific T cells within the CNS during acute viral-induced
encephalomyelitis. FTY720 treatment reduces the severity of neuroinflammatory
mediated demyelination by restricting the access of disease-causing lymphocytes
into the CNS but is not associated with viral recrudescence in this model.
PMID- 25138357
TI - Yeast studies reveal moonlighting functions of the ancient actin cytoskeleton.
AB - Classic functions of the actin cytoskeleton include control of cell size and
shape and the internal organization of cells. These functions are manifest in
cellular processes of fundamental importance throughout biology such as the
generation of cell polarity, cell migration, cell adhesion, and cell division.
However, studies in the unicellular model eukaryote Saccharomyces cerevisiae
(Baker's yeast) are giving insights into other functions in which the actin
cytoskeleton plays a critical role. These include endocytosis, control of protein
translation, and determination of protein 3-dimensional shape (especially
conversion of normal cellular proteins into prions). Here, we present a concise
overview of these new "moonlighting" roles for the actin cytoskeleton and how
some of these roles might lie at the heart of important molecular switches. This
is an exciting time for researchers interested in the actin cytoskeleton. We show
here how studies of actin are leading us into many new and exciting realms at the
interface of genetics, biochemistry, and cell biology. While many of the
pioneering studies have been conducted using yeast, the conservation of the actin
cytoskeleton and its component proteins throughout eukaryotes suggests that these
new roles for the actin cytoskeleton may not be restricted to yeast cells but
rather may reflect new roles for the actin cytoskeleton of all eukaryotes.
PMID- 25138358
TI - How to choose an anesthesia ventilator?
AB - During the past few years, many manufacturers have developed a new generation
anesthesia ventilators or anesthesia workstations with innovative technology and
introduced so-called new ventilatory modes in the operating room. The aim of this
article is to briefly explain how an anesthesia ventilator works, to describe the
main differences between the technologies used, to describe the main criteria for
evaluating technical and pneumatic performances and to list key elements not to
be forgotten during the process of acquiring an anesthesia ventilator.
PMID- 25138359
TI - Large Urethro-Vesico-Vaginal Fistula due to a Vaginal Foreign Body in a 22-Year
Old Woman: Case Report and Literature Review.
AB - In the non-industrialized countries of Africa and Asia obstetric fistulas are
more frequently caused by prolonged labour, whereas in countries with developed
healthcare systems they are generally the result of complications of
gynaecological surgery or, rarely, benign pathologies like inflammation or
foreign bodies. A 22-year-old woman was brought to the gynaecology clinic because
of foul-smelling vaginal discharge. On pelvic examination a ring-like foreign
body was impacted between the anterior and posterior vaginal wall. MRI scan
confirmed the presence of a cylindrical foreign body in the vagina and the
patient revealed that she had 'involuntarily' inserted a plastic bubble bath cap
into the vagina. At surgery removal of the cap was difficult and at the end of
the manoeuver evidence of a huge urethro-vesico-vaginal fistula occurred. The
patient was discharged with bilateral ureteral stents and suprapubic catheter.
After 3 months we performed an end-to-end anastomotic urethroplasty to repair the
urethral avulsion and restored the bladder/trigonal and vaginal/cervical defects
with 3 layers of sutures; 3 months later the patient had no complaints. Complex
genital fistulas represent an extremely debilitating morbidity. In our case, a
vaginal approach was successful, but the choice between an abdominal or vaginal
approach depends on the surgeon's experience and training.
PMID- 25138360
TI - Editorial.
PMID- 25138361
TI - Biomechanics of incisor retraction with mini-implant anchorage.
AB - Mini-implants have been successfully incorporated into orthodontic practice all
over the world. One of the most popular applications of mini-implant anchorage is
to facilitate retraction of the anterior teeth. This article reviews the
mechanics involved in anterior tooth retraction with mini-implant supported
anchorage. An attempt has been made to synthesize information available in the
literature and present it in a manner that is easily understandable from a
clinical perspective. We discuss the fundamental differences mini-implant based
incisor retraction has when compared to conventional techniques, mechanical
factors affecting this process and provide a step-by-step analysis of incisor
retraction. In addition, various models of space closure are discussed that have
evolved through careful evaluation of in vitro and in vivo experiments.
PMID- 25138362
TI - An active, skeletally anchored transpalatal appliance for derotation,
distalization and vertical control of maxillary first molars.
AB - OBJECTIVE: The objective of this investigation was to evaluate treatment outcomes
of the skeletally anchored 'Frog' appliance. DESIGN: A single-centre,
retrospective study was performed. SETTING: Private orthodontic practice.
PARTICIPANTS: Patients who had undergone comprehensive orthodontic treatment with
the skeletally anchored 'Frog' appliance. METHODS: 43 participants (20 males and
23 females) who had received treatment with the skeletally anchored 'Frog'
appliance where included. In order to explore dentoalveolar and skeletal
treatment outcomes, pre- (T1) and post- (T2) treatment measurements were
performed on patients' plaster models and cephalometric images. Comparisons
between T1 and T2 were made by means of a Student's t-test. All statistical
analyses were conducted at the 0.05 level of statistical significance. RESULTS:
Study model analysis revealed a statistically significant derotation of maxillary
molars (MUDeltaT2-T1=9.5 degrees , P<0.001) as well as an increase in transverse
arch dimensions at the end of treatment (MUDeltaT2-T1=2.2 mm, P<0.001).
Cephalometric changes included bodily distalization of maxillary molars
(MUDelta(T2-T1)=-1.9 mm, P<0.001), as well as noticeable angular displacement
(MUDeltaT2-T1=4.1 degrees , P=0.004). No significant anchorage loss was observed,
as displayed by the limited change in maxillary incisor position (MUDelta(T1
T2)=0.2 mm, P=0.45). In addition, excellent vertical control of the maxillary
molars was achieved, with no change in the mandibular plane (ML/NSL) angle
(MUDeltaT2-T1=0.3 degrees , P=0.38). CONCLUSIONS: The skeletal 'Frog' is
effective in derotating and distalizing maxillary molars without anchorage loss
and with excellent vertical control.
PMID- 25138363
TI - Hard and soft tissue considerations at mini-implant insertion sites.
AB - Various factors influence where orthodontic mini-implants will be placed. This
article highlights the pertinent variables that should find consideration when
planning the placement of orthodontic mini-implants.
PMID- 25138364
TI - Clinical outcomes of cases with missing lateral incisors treated with the 'T'
Mesialslider.
AB - The objective of this article is to review the fabrication and activation
procedures of the 'T'-Mesialslider and to present the clinical outcomes in cases
where canine substitution is the treatment of choice for missing maxillary
lateral incisors. The 'T'-Mesialslider allows for effective mesial translation of
the canines and the posterior dentition, without significant loss of anterior
anchorage and with good vertical control. Possible adverse effects of the
appliance and clinical recommendations for their management are also discussed.
In canine substitution cases with high anchorage demands, the 'T'-Mesialslider
provides an effective treatment option.
PMID- 25138365
TI - Molar intrusion in the management of anterior openbite and 'high angle' Class II
malocclusions.
AB - Orthodontic correction of anterior openbite has conventionally involved
extraction therapy or an adjunctive maxillary impaction osteotomy. However, bone
anchored molar intrusion treatments have been reported in recent years as a less
invasive alternative for such patients. This paper describes the concepts and
treatment processes involved with mini-implant molar intrusion to correct
anterior openbite and reduce patients' excessive vertical facial proportions.
PMID- 25138366
TI - The Hybrid Hyrax Distalizer, a new all-in-one appliance for rapid palatal
expansion, early class III treatment and upper molar distalization.
AB - Growing class III patients with maxillary deficiency may be treated with a
maxillary protraction facemask. Because the force generated by this appliance is
applied to the teeth, the inevitable mesial migration of the dentition can result
in anterior crowding, incisor proclination and a possible need for subsequent
extraction therapy. The Hybrid Hyrax appliance, anchored on mini-implants in the
anterior palate, can be used to overcome these side-effects during the facemask
therapy. In some class III cases, there is also a need for subsequent
distalization after the orthopaedic treatment. In this paper, clinical
application of the Hybrid Hyrax Distalizer is described, facilitating both
orthopaedic advancement of the maxilla and simultaneous orthodontic distalization
of the maxillary molars.
PMID- 25138367
TI - Mini-implant applications in orthognathic surgical treatment.
AB - Orthognathic surgical treatment conventionally relies on the use of full arch
fixed orthodontic appliances. However, the introduction of orthodontic mini
implants has altered surgical options in terms of providing an alternative to
fixation (intermaxillary fixation, IMF) screws and even to maxillary osteotomy.
This paper describes the integration of mini-implants within orthognathic
treatments in terms of 'surgery first' treatments and by introducing the concept
of the conversion of bimaxillary cases into mandible-only surgery treatments.
PMID- 25138368
TI - Temporary replacement of missing maxillary lateral incisors with orthodontic
miniscrew implants in growing patients: rationale, clinical technique, and long
term results.
AB - The missing maxillary lateral incisor in adolescent patients presents an
orthodontic challenge. Historically, there have been three treatment options to
address this clinical problem: (1) canine substitution, (2) tooth auto
transplantation, and (3) dental restoration. Unfortunately, these methods are not
without limitation. A novel treatment concept, originating in 2003 and utilizing
orthodontic miniscrew implants, is presented along with the rationale, clinical
technique and 8 years of follow-up.
PMID- 25138369
TI - Translational mini-screw implant research.
AB - It is important to thoroughly test new materials as well as techniques when these
innovations are to be utilized in the human clinical situation. Translational
research fills this important niche. The purpose of translational research is to
establish the continuity of evidence from the laboratory to the clinic and in so
doing, provide evidence that the material is functioning appropriately and that
the process in the human will be successful. This concept applies to the mini
screw implant; which, has been very successfully introduced into the orthodontic
armamentarium over the last decade for application as a temporary anchorage
device. The examples of translational research that will be illustrated in this
paper have paved the way to ensure that clinicians have evidence to confidently
utilize mini-screw implants in orthodontic practice. Needless to say, more
studies are needed to ensure a safe, effective and efficient manner to practice
orthodontics.
PMID- 25138371
TI - Resveratrol treatment as an adjunct to pharmacological management in type 2
diabetes mellitus--systematic review and meta-analysis.
AB - The red wine polyphenol, resveratrol, is highly effective in treating type 2
diabetes mellitus (T2DM) in animal models, but there is no consensus regarding
its efficacy in humans. We conducted a systematic review, which included searches
in nine scholarly databases and six clinical trial registries, and identified
randomized controlled clinical trials whereby resveratrol was used as an adjunct
to pharmaceutical interventions in T2DM. Meta-analysis on clinical parameters was
performed for available data. Of 764 articles originally identified, data from
six unique datasets, examining a total of 196 T2DM patients (104 resveratrol, 92
control/placebo) ultimately met inclusion criteria. Statistically significant (p
< 0.05) positive effects, indicating that resveratrol supplementation was more
effective than placebo/control, were identified for systolic blood pressure,
hemoglobin A1c, and creatinine, but not for fasting glucose, homeostatic model
assessment of insulin resistance, diastolic blood pressure, insulin,
triglycerides, LDL, or HDL cholesterol. No major adverse events were reported and
side effects of resveratrol were not different than placebo/control. Though
limitations in sample size and treatment duration preclude definitive changes in
clinical practice, significant improvements in multiple cardiometabolic
biomarkers and an excellent safety profile support resveratrol as a leading
candidate as an adjunct to pharmacological management of T2DM.
PMID- 25138370
TI - Non-HLA genes PTPN22, CDK6 and PADI4 are associated with specific autoantibodies
in HLA-defined subgroups of rheumatoid arthritis.
AB - INTRODUCTION: Genetic susceptibility to complex diseases has been intensively
studied during the last decade, yet only signals with small effect have been
found leaving open the possibility that subgroups within complex traits show
stronger association signals. In rheumatoid arthritis (RA), autoantibody
production serves as a helpful discriminator in genetic studies and today anti
citrullinated cyclic peptide (anti-CCP) antibody positivity is employed for
diagnosis of disease. The HLA-DRB1 locus is known as the most important genetic
contributor for the risk of RA, but is not sufficient to drive autoimmunity and
additional genetic and environmental factors are involved. Hence, we addressed
the association of previously discovered RA loci with disease-specific
autoantibody responses in RA patients stratified by HLA-DRB1*04. METHODS: We
investigated 2178 patients from three RA cohorts from Sweden and Spain for 41
genetic variants and four autoantibodies, including the generic anti-CCP as well
as specific responses towards citrullinated peptides from vimentin, alpha-enolase
and type II collagen. RESULTS: Our data demonstrated different genetic
associations of autoantibody-positive disease subgroups in relation to the
presence of DRB1*04. Two specific subgroups of autoantibody-positive RA were
identified. The SNP in PTPN22 was associated with presence of anti-citrullinated
enolase peptide antibodies in carriers of HLA-DRB1*04 (Cochran-Mantel-Haenszel
test P = 0.0001, P corrected <0.05), whereas SNPs in CDK6 and PADI4 were
associated with anti-CCP status in DRB1*04 negative patients (Cochran-Mantel
Haenszel test P = 0.0004, P corrected <0.05 for both markers). Additionally we
see allelic correlation with autoantibody titers for PTPN22 SNP rs2476601 and
anti-citrullinated enolase peptide antibodies in carriers of HLA-DRB1*04 (Mann
Whitney test P = 0.02) and between CDK6 SNP rs42041 and anti-CCP in non-carriers
of HLA-DRB1*04 (Mann Whitney test P = 0.02). CONCLUSION: These data point to
alternative pathways for disease development in clinically similar RA subgroups
and suggest an approach for study of genetic complexity of disease with strong
contribution of HLA.
PMID- 25138372
TI - Human mate selection and addiction: a conceptual critique.
AB - The authors review past work on modeling human mate selection, and suggest, using
illustrations from existing literature on the impact of alcoholism on
relationship formation and dissolution and reproduction, that the challenges of
adequately characterizing human mate selection have not yet been overcome. Some
paths forwards are suggested.
PMID- 25138373
TI - Early erythropoietin in post-diarrheal hemolytic uremic syndrome: a case-control
study.
AB - BACKGROUND: Although erythropoietin (EPO) deficiency has been reported in
children with post-diarrheal hemolytic uremic syndrome (D + HUS), very limited
clinical data on EPO use in this disease are currently available. In this case
control study we examined whether EPO administration would reduce the number of
red blood cell (RBC) transfusions in D + HUS patients under our care. METHODS:
Data from children treated exclusively with RBC transfusions (controls; n = 21)
were retrospectively compared with data on those who also received EPO for the
treatment of anemia (cases; n = 21). RESULTS: Both patient groups were similar in
age (p = 0.9), gender (p = 0.12), weight (p = 1.00) and height (p = 0.66). Acute
phase severity was also comparable, as inferred by the need for dialysis (p =
0.74), the duration of dialysis (p = 0.3), length of hospitalization (p = 0.81),
presence of severe bowel (p = 1.00) or neurological injury (p = 0.69), arterial
hypertension (p = 1.00) and death (p = 1.00). No differences in the hemoglobin
level at admission (p = 0.51) and discharge (p = 0.28) were noted. Three children
treated with EPO and two controls did not require any RBC transfusion (p = 1.00).
Median number of RBC transfusions needed by cases and controls was 2 (p = 0.52).
CONCLUSION: Treatment with EPO did not reduce the number of RBC transfusions in D
+ HUS children. Assessment of EPO efficacy in D + HUS merits further studies.
PMID- 25138374
TI - Mechanism of the palladium-catalyzed hydrothiolation of alkynes to thioethers: a
DFT study.
AB - The mechanisms of the palladium-catalyzed hydrothiolation of alkynes with thiols
were investigated using density functional theory at the B3LYP/6-31G(d, p) (SDD
for Pd) level. Solvent effects on these reactions were explored using the
polarizable continuum model (PCM) for the solvent tetrahydrofuran (THF).
Markovnikov-type vinyl sulfides or cis-configured anti-Markovnikov-type products
were formed by three possible pathways. Our calculation results suggested the
following: (1) the first step of the cycle is a proton-transfer process from
thiols onto the palladium atom to form a palladium-thiolate intermediate. The
palladium-thiolate species is attacked on alkynes to obtain an elimination
product, liberating the catalyst. (2) The higher activation energies for the
alkyne into the palladium-thiolate bond indicate that this step is the rate
determining step. The Markovnikov-type vinyl sulfide product is favored. However,
for the aromatic alkyne, the cis-configured anti-Markovnikov-type product is
favored. (3) The activation energy would reduce when thiols are substituted with
an aromatic group. Our calculated results are consistent with the experimental
observations of Frech and colleagues for the palladium-catalyzed hydrothiolation
of alkynes to thiols.
PMID- 25138375
TI - DFT study of the per-6-amino-beta-cyclodextrin as catalyst in synthesis of 2-aryl
2,3-dihydro-4-quinolones.
AB - The synthesis of 2-aryl-2,3-dihydro-4-quinolones in the presence of per-6-amino
beta-cyclodextrin (per-6-ABCD) as catalyst can improve selectivity and yield. The
interaction between per-6-ABCD and benzaldehyde or o-aminoacetophenone plays an
important role in this reaction. This paper studies the complexes of per-6-ABCD
with benzaldehyde and o-aminoacetophenone using density functional theory (DFT)
method. The reaction process is investigated by studying the energy of the
reactants and the product. Hydrogen bonds are researched on the basis of natural
bonding orbital (NBO) analysis, the results propose the donor-acceptor
interactions of complex. The Mulliken charge and frontier orbital are employed
for revealing the charge distribution. In addition, (13)C nuclear magnetic
resonance ((13)CNMR) spectroscopy shows that the carbon atom on the aldehyde
group for benzaldehyde, carbonyl group and the carbon atom connected with
carbonyl group for o-aminoacetophenone are apparently activated in the cavity of
per-6-ABCD. The probable catalytic mechanism of per-6-ABCD is discussed in terms
of the calculated parameters.
PMID- 25138376
TI - Measurement of neck circumference and its correlation with body composition in a
sample of students in Sao Paulo, Brazil.
AB - PURPOSE: The purpose of this study was to verify the correlation between neck
circumference (NC) and body mass index (BMI) in children, and to determine NC
percentiles for Brazilian children. METHODS: The subjects of this cross-sectional
study were students between the ages of 6 and 19 years from five schools in Sao
Paulo, Brazil. Clinical and anthropometric data were collected from the students
from April 2011 to June 2012. NC was measured at the level of the cricoid
cartilage. We calculated Pearson correlation coefficients between NC and other
indices of obesity with Sigma Stat 3.5. NC percentiles were produced using the
LMS (lambda, mu, and sigma) method (STATA 12.0). RESULTS: Among 2,794 students,
49.9% were male. NC was significantly correlated with age, BMI, waist
circumference (WC), and body fat percentage (%BF). The NC of boys was greater
than that of girls. The NC curves of smoothed 3rd, 10th, 25th, 50th, 75th, 90th,
and 97th percentiles were constructed by age and sex. CONCLUSIONS: NC can be used
in the assessment of obesity in childhood. There was a positive correlation
between NC and BMI, WC and %BF. This study was the first to provide NC
percentiles for children in Brazil.
PMID- 25138377
TI - The effectiveness of community-based loan funds for transport during obstetric
emergencies in developing countries: a systematic review.
AB - OBJECTIVE: Scarcity and costs of transport have been implicated as key barriers
to accessing care when obstetric emergencies occur in community settings.
Community-based loans have been used to increase utilization of health facilities
and potentially reduce maternal mortality by providing funding at community level
to provide emergency transport. This review aimed to provide evidence of the
effect of community-based loan funds on utilization of health facilities and
reduction of maternal mortality in developing countries. METHODS: Electronic
databases of published literature and websites were searched for relevant
literature using a pre-defined set of search terms, inclusion and exclusion
criteria. Screening of titles, abstracts and full-text articles were done by at
least two reviewers independently. Quality assessment was carried out on the
selected papers. Data related to deliveries and obstetric complications attended
at facilities, maternal deaths and live births were extracted to measure and
compare the effects of community-based loan funds using odds ratios (ORs) and
reductions in maternal mortality ratio. Forest plots are presented where
possible. RESULTS: The results of the review show that groups where community
based loan funds were implemented (alongside other interventions) generally
recorded increases in utilization of health facilities for deliveries, with ORs
of 3.5 (0.97-15.48) and 3.55 (1.56-8.05); and an increase in utilization of
emergency obstetric care with ORs of 2.22 (0.51-10.38) and 3.37 (1.78-6.37).
Intervention groups also experienced a positive effect on met need for
complications and a reduction in maternal mortality. CONCLUSION: There is some
evidence to suggest that community-based loan funds as part of a multifaceted
intervention have positive effects. Conclusions are limited by challenges of
study design and bias. Further studies which strengthen the evidence of the
effects of loan funds, and mechanism for their functionality, are recommended.
PMID- 25138380
TI - Abstracts of the American Academy for Cerebral Palsy and Developmental Medicine
68th Annual Meeting, 10-13 September, 2014, San Diego, California, USA.
PMID- 25138378
TI - Ganoderic acid Me induces the apoptosis of competent T cells and increases the
proportion of Treg cells through enhancing the expression and activation of
indoleamine 2,3-dioxygenase in mouse lewis lung cancer cells.
AB - The indoleamine 2,3-dioxygenase-(IDO-) mediated microenvironment plays an
important role in tumor immune escape. It is known that ganoderic acid Me can
enhance IFN-gamma expression and IDO is preferentially induced by IFN-gamma.
However, whether GA-Me can induce IDO expression has not been clarified yet. We
established stable clones of IDO-overexpressing 2 LL cells (2LL-EGFP-IDO). After
co-culturing with IDO expressing or control vector-transfected 2LL-EGFP cells, T
cell apoptosis was determined and the proportion of the regulatory T cells
(Tregs) and CD8+ T cell subset was measured. The total cellular protein samples
of 2 LL-EGFP-IDO cells were isolated for detecting JAK-STAT1 signalling pathway.
Co-culture supernatants were used to detect amino acids and cytokines. IDO
transfected 2 LL cells yielded high level of IDO enzymatic activity, resulting in
complete depletion of tryptophan from the culture medium. We found that apoptosis
occurred in T cells after cocultured with IDO+2LL cells and the proportion of
CD4+CD25+ cells and FoxP3+ cells increased while CD8+ cells decreased. The
specific inhibitor of IDO, 1-D-MT and GA-Me efficiently enhanced T cell
apoptosis, increased Tregs, and reduced CD8+ T cells in vitro. Increased
expression of IDO, p-JAK1 and p-STAT1 were confirmed by Western blot analysis.
The levels of IFN-gamma, IL-10, LDH and kynurenine in co-culture supernatant
correspondingly increased, while tryptophan reduced. These results suggest that
GA-Me contributing to IDO helps to create a tolerogenic milieu in lung tumors by
directly inducing T cell apoptosis, restraining CD8+ T cell activation, and
enhancing Treg-mediated immunosuppression.
PMID- 25138381
TI - West Nile virus: should pediatricians care?
AB - Given the recurrent serious outbreaks of West Nile Virus (WNV) in the United
States over the past decade, the spread to Canada and South America, the
recurrent outbreaks in Europe, and the potential for serious neurological disease
even in children under 18 years, paediatricians in affected areas must consider
WNV in the differential diagnosis of all children presenting with aseptic
meningitis, encephalitis and acute flaccid paralysis. Additionally, given that
WNV encephalitis can occur after WNV infection, suspicion for neurological WNV
disease must remain high even after otherwise benign febrile illnesses if the
child lives in or has traveled to an affected region. Under-diagnosis in the
pediatric population is likely a serious problem, necessitating further
educational efforts. More follow-up studies of WNV neurological disease in
children and youth are needed to better understand the potential long-term
sequelae during vulnerable times of neurodevelopment and neural remodeling.
Similarly, more research is need on short and long-term fetal outcomes of
maternal WNV infection.
PMID- 25138382
TI - The association of major patterns of physical activity, sedentary behavior and
sleep with health-related quality of life: a cohort study.
AB - OBJECTIVE: To examine the prospective association of patterns of physical
activity, sedentary behavior and sleep with health-related quality of life (HRQL)
in the general population of Spain. METHODS: A cohort study with 4271 individuals
aged >= 18 years was recruited in 2008-2010 and followed-up prospectively through
2012. Activity patterns were derived from factor analysis. HRQL was assessed with
the SF-12 questionnaire, and suboptimal HRQL was defined as a score below the sex
specific sample median. RESULTS: Three main activity patterns were identified. A
higher adherence to the pattern named "vigorous activity-seated at the computer"
was inversely associated with a suboptimal score in the physical-composite
summary (PCS) of the SF-12 (multivariate adjusted odds ratio [aOR] for the
highest vs. the lowest quartile 0.71; 95% confidence interval [IC] 0.55-0.90; p
trend=0.003). The "light activity-seated for reading" pattern was inversely
associated with a suboptimal score in the mental-composite summary (aOR=0.73; 95%
CI=0.61-0.89; p-trend=0.002). However, a higher adherence to the "seated for
watching TV-daytime sleeping" pattern was directly associated with suboptimal PCS
(aOR=1.35; 95% CI=1.10-1.66; p-trend=0.008). CONCLUSION: Patterns including any
physical activity were associated with better physical or mental HRQL. However, a
pattern defined by sedentary behavior with diurnal sleep showed worse HRQL and
should be a priority target of preventive interventions.
PMID- 25138384
TI - Hematologic findings predictive of bone marrow disease in dogs with multicentric
large-cell lymphoma.
AB - BACKGROUND: Evaluation of the bone marrow is needed for complete staging in dogs
with multicentric large-cell lymphoma, but is often omitted in clinical practice.
OBJECTIVES: The objective was to determine if routine peripheral blood findings,
including microscopic evaluation of blood smears, can predict the presence of
bone marrow involvement in dogs with lymphoma. METHODS: Hematologic data
including evaluation of blood smears and bone marrow aspirates from 107 dogs
newly diagnosed with large-cell lymphoma were retrospectively evaluated.
Neoplastic lymphocytes were identified based on cell size, nuclear size,
chromatin pattern, and the presence of nucleoli. Positive specimens were defined
as having >= 10% neoplastic lymphocytes. Two groups were established based on the
presence or absence of lymphoma in the bone marrow. Variables (positive blood
smear, HCT, platelet count, and total and differential WBC counts) were evaluated
to determine if they were predictive of bone marrow involvement using univariate
and multivariate logistic models. RESULTS: Thrombocytopenia and the presence of >
10% neoplastic lymphocytes on blood smears were identified as significant
variables for predicting the presence of bone marrow involvement. When considered
independently, either a positive blood smear or thrombocytopenia had low
sensitivity (60%) and moderate specificity (89% and 87%, respectively).
Sensitivity increased when these variables were evaluated together (80%).
CONCLUSIONS: In dogs with multicentric large-cell lymphoma, thrombocytopenia or
the presence of neoplastic lymphocytes in circulation is suggestive of bone
marrow involvement, but not definitive. Normal peripheral blood findings do not
exclude the possibility of lymphoma in the bone marrow.
PMID- 25138383
TI - Possibilities for discrimination between chewing of coca leaves and abuse of
cocaine by hair analysis including hygrine, cuscohygrine, cinnamoylcocaine and
cocaine metabolite/cocaine ratios.
AB - Contrary to the illegal use of any form of manufactured cocaine, chewing of coca
leaves and drinking of coca tea are allowed and are very common and socially
integrated in several South American countries. Because of this different legal
state, an analytical method for discrimination between use of coca leaves and
abuse of processed cocaine preparations is required. In this study, the
applicability of hair analysis for this purpose was examined. Hair samples from
26 Argentinean coca chewers and 22 German cocaine users were analysed for cocaine
(COC), norcocaine (NC), benzoylecgonine (BE), ecgonine methyl ester (EME),
cocaethylene (CE), cinnamoylcocaine (CIN), tropacocaine (TRO), cuscohygrine (CUS)
and hygrine (HYG) by hydrophilic interaction liquid chromatography (HILIC) in
combination with triplequad mass spectrometry (MS/MS) and hybrid quadrupole time
of-flight mass spectrometry (QTOF-MS). The following concentrations (range,
median, ng/mg) were determined in hair of the coca chewers: COC 0.085-75.5, 17.0;
NC 0.03-1.15, 0.12; BE 0.046-35.5, 6.1; EME 0.014-6.0, 0.66; CE 0.00-13.8, 0.38;
CIN 0.005-16.8, 0.79; TRO 0.02-0.16, 0.023; CUS 0.026-26.7, 0.31. In lack of a
reference substance, only qualitative data were obtained for HYG, and two
metabolites of CUS were detected which were not found in hair of the cocaine
users. For interpretation, the concentrations of the metabolites and of the coca
alkaloids in relation to cocaine were statistically compared between coca chewers
and cocaine users. By analysis of variance (ANOVA) significant differences were
found for all analytes (alpha = 0.000 to 0.030) with the exception of TRO (alpha
= 0.218). The ratios CUS/COC, CIN/COC and EME/COC appeared to be the most
suitable criteria for discrimination between both groups with the means and
medians 5-fold to 10-fold higher for coca chewers and a low overlap of the ranges
between both groups. The same was qualitatively found for HYG. However, these
criteria cannot exclude cocaine use in addition to coca chewing. In this regard
screening for typical cutting agents can be helpful and led to the detection of
levamisole (21*), lidocaine (6*) and paracetamol (3*) in the 22 samples from
German cocaine users, whereas no levamisole, lidocaine (3*) and paracetamol (1*)
were found in hair from the Argentinean coca chewers. These criteria have to be
confirmed for South American cocaine consumers including smokers of coca paste
and may be different because of different composition of the drug and other use
habits.
PMID- 25138385
TI - Absorption spectrophotometric, fluorescence and quantum chemical investigations
on non-covalent interaction between PC70BM and designed diporphyrin in solution.
AB - Present work reports the photophysical insights on supramolecular interaction of
a C70 derivative, namely, [6,6]-phenyl C71 butyric acid methyl ester (PC70BM),
with two designed diporphyrin molecules having dithiophene (1) and carbazole (2)
spacer in toluene and benzonitrile. Both absorption spectrophotometric and steady
state fluorescence investigations reveal efficient complexation of PC70BM with 1
and 2 in both toluene and benzonitrile. The magnitude of average value of binding
constant, viz., Kav, for the complexes of PC70BM with 1 and 2 in toluene
(benzonitrile) are estimated to be 2.185 * 10(3)dm(3)mol(-1) (3.215 *
10(3)dm(3)mol(-1)) and 10.180 * 10(3)dm(3)mol(-1) (25.405 * 10(3)dm(3)mol(-1)),
respectively. Selectivity in binding for the complexation process of PC70BM with
1 and 2 is estimated to be ~4.6 and ~7.90 as observed in toluene and
benzonitrile, respectively. The complexation between PC70BM and diporphyrin is
well accounted by a theoretical model which takes into account the electronic
subsystems of both acceptor and donor. Ab initio calculations in vacuo establish
that size selective orientation pattern of PC70BM towards the cavity of
diporphyrin dictates the magnitude of binding and electronic structure of the
PC70BM/diporphyrin complexes.
PMID- 25138386
TI - Beyond barriers: fundamental 'disconnects' underlying the treatment of breast
cancer patients' sexual health.
AB - Sexual health concerns represent one of the most frequently experienced and
longest-lasting effects of breast cancer treatment, but research suggests that
service providers rarely discuss sexual health with their patients. Existing
research examining barriers to addressing patients' sexual health concerns has
focused on discrete characteristics of the provider-patient interaction without
considering the broader context in which these interactions occur. Drawing on the
experiences of 21 breast cancer survivors, this paper explores three ways in
which fundamental cultural and structural characteristics of the cancer care
system in the USA may prevent breast cancer survivors from addressing their
sexual health concerns, including: (1) when patients discussed sexual health with
their providers, their providers approached sexuality as primarily physical,
while participants experienced complex, multidimensional sexual health concerns;
(2) specialisation within cancer care services made it difficult for patients to
identify the appropriate provider to address their concerns; and (3) the
structure of cancer care literally disconnects patients from the healthcare
system at the time when sexual side effects commonly emerged. These data suggest
that addressing breast cancer survivors' sexual health concerns requires a
multifaceted approach to health systems change.
PMID- 25138387
TI - [Listeria monocytogenes and its relationship with non-biological therapy in
inflammatory bowel disease].
PMID- 25138388
TI - Age-related pattern and monocyte-acquired haemozoin associated production of
erythropoietin in children with severe malarial anaemia in Ghana.
AB - BACKGROUND: Malaria continues to be a global health challenge, affecting more
than half the world's population and causing approximately 660,000 deaths
annually. The majority of malaria cases are caused by Plasmodium falciparum and
occur in sub-Saharan Africa. One of the major complications asscociated with
malaria is severe anaemia, caused by a cycle of haemoglobin digestion by the
parasite. Anaemia due to falciparum malaria in children has multifactorial
pathogenesis, which includes suppression of bone marrow activity. Recent studies
have shown that haemozoin, which is a by-product of parasite haemoglobin
digestion, may play an important role in suppression of haemoglobin production,
leading to anaemia. In this study we correlated the levels of erythropoietin
(EPO), as an indicator of stimulation of haemoglobin production, to the levels of
monocyte acquired haemozoin in children with both severe and uncomplicated
malaria. There was a significantly negative correlation between levels of
haemozoin-containing monocytes and EPO, which may suggest that haemozoin
suppresses erythropoiesis in severe malaria. A multiple linear regression
analysis and simple bar was used to investigate associations between various
haematological parameters. METHODS: To examine the levels of erythropoietin in
the age categories, the levels of erythropoietin was measured using a commercial
Enyme-Linked Immunosorbent Assay (ELISA). Giemsa-stained blood smears were used
to determine percentage pigment containing monocytes. The haemozoin containing
monocytes was expressed as a percentage of the total number of monocytes. To
obtain the number of haemozoin containing monocytes/MUL the percentage of
haemozoin containing monocytes was multiplied by the absolute number of
monocytes/MUL from the automated haematology analyzer. RESULTS: The levels of
erythropoietin in younger children (<3 years) was significantly higher than in
older children with a similar degree of malaria anaemia (Hb levels) (p < 0.005).
Haemozoin-containing monocytes were relatively higher in severe malaria anaemia
patients compared to those with uncomplicated malaria (p < 0.001). CONCLUSIONS:
Age purportedly has a direct effect on background levels of erythropoietin. With
corresponding decreased levels of erythropoietin in older children with the same
degree of severe malarial anaemia, conceivably, the bone marrows of younger
children with acute malaria may be less sensitive to erythropoietin.
PMID- 25138389
TI - A health-economic analysis of diagnosis and treatment of obstructive sleep apnea
with continuous positive airway pressure in relation to cardiovascular disease.
The Greek experience.
AB - PURPOSE: Obstructive sleep apnea syndrome (OSAS) is common in adult population
and it is associated with increased morbidity and mortality, especially due to
cardiovascular disease (CVD). Both diagnosis, based on polysomnography, and
treatment with continuous positive airway pressure (CPAP), carry a potentially
high cost. The present study aims to analyze the cost-effectiveness of CPAP
treatment versus no treatment, in the long-term, as it examines the effect of
this treatment on the incidence of CVD. METHODS: A Markov model was constructed
to observe the disease evolution in patients with OSAS based on published
evidence. Data on treatment costs were collected from public hospitals in Greece.
Within each cycle of the model, each patient may remain free of CVD, may develop
CVD, may die due to a cause related to CVD, or may die from other causes. The
model begins at the age of 55 years in a severe OSAS patient (apnea-hypopnea
index >=30/h) and lasts for 45 years. RESULTS: Within the limitation of the
model, CPAP was found to be a cost-effective strategy versus no treatment, due to
the reduction of the cost for the CVD treatment, when the analysis was restricted
to the male population. Moreover, CPAP was found to be clinically more effective
than no treatment, as it increases life expectancy in both males and females.
CONCLUSIONS: CPAP was found to be clinically more effective therapy than no
treatment in relation to CVD and a cost-effective strategy in males with severe
OSAS.
PMID- 25138390
TI - The role of pharmacies and pharmacists in managing controlled substance
dispensing.
AB - The epidemic of prescription opioid-related morbidity and mortality demonstrates
the need for a fresh, open, and balanced approach to managing pain while
minimizing adverse personal and public health outcomes. Interventions by
pharmacists in situations in which prescriptions are felt to be inappropriate
have raised the ire of prescribers who feel their professional judgment is being
questioned and their time is being usurped from patient care. Pharmacists,
however, represent an important check and balance in the opioid analgesic
prescribing chain, and prescribers should embrace their involvement and recognize
that the time and effort of the pharmacist are directed at improving care of
individual patients and keeping a watchful eye on the public health. Pharmacies
need to keep a mindful eye toward professional practices of physicians and use
noninvasive means, such as database inquiries, prior to directly contacting a
prescriber. Collaboration is the most professional approach that can be taken to
assure that our joint priority of caring for patients in distress will be
accomplished effectively and safely.
PMID- 25138391
TI - Lung cancer screening with low-dose CT (LDCT), or when a public health
intervention is beyond the patient's benefit.
PMID- 25138392
TI - Passive smoking assessed by salivary cotinine and self-report in relation to
cause-specific mortality: 17-year follow-up of study participants in the UK
Health and Lifestyle Survey.
AB - BACKGROUND: Evidence that passive smoking is a risk factor for cardiovascular
disease and selected cancers is largely derived from studies in which this
exposure is self-reported. Objective assessment using biochemical techniques may
yield a more accurate estimate of risk, although each approach has its strengths
and weaknesses. We examined the association of salivary cotinine, a widely
utilised biomarker for passive smoking, and self-reported passive smoking in the
home, with mortality from all causes, cardiovascular disease and all cancers
combined. METHODS: In 1992, investigators on the UK Health and Lifestyle Survey
collected data on salivary cotinine, self-reported smoking (direct and passive)
and a range of covariates in 3731 men and women aged 25 years and over. Mortality
was ascertained using linkage to national death records. RESULTS: Analyses were
based on 2523 individuals (1433 [57%] women) who classified themselves as non
smokers (never and former). Seventeen years of follow-up gave rise to 588 deaths
(253 from cardiovascular disease and 146 from cancer). In men, adjusted hazard
ratios (HR) for the association between cotinine levels (1.3-15.0 [high] vs <=0.3
[low] ng/mL) and the various mortality outcomes were weak for total mortality
(HR; 95% CI: 1.22; 0.91 to 1.64) and cardiovascular disease (1.25; 0.78 to 1.99)
and absent for all cancers combined (1.10; 0.61 to 2.00). Corresponding
associations were generally stronger when self-reported passive smoking (some vs
none) was the exposure of interest: 1.53 (1.12 to 2.08), 1.88 (1.20 to 2.96) and
1.58 (0.85 to 2.93). The pattern of association for women in both sets of
analyses was less consistent. CONCLUSIONS: In men in the present study, compared
with our biochemical marker of passive smoking, cotinine, mortality was generally
more consistently associated with self-reported passive smoking.
PMID- 25138393
TI - Goals and grades for medical teachers.
PMID- 25138394
TI - [Re: The animal welfare act should be expanded to include children].
PMID- 25138395
TI - [G.E. Berge replies].
PMID- 25138396
TI - [Re: Wise suggestions about abortion referral].
PMID- 25138397
TI - [Re: The psychiatrist role in crisis].
PMID- 25138398
TI - [Re: Renal sympathetic denervation in treatment-resistant hypertension].
PMID- 25138400
TI - [Dental health when using bisphosphonates against breast cancer].
PMID- 25138401
TI - [Differences in treatment of stroke].
PMID- 25138402
TI - [Medication Reconciliation--important measure for better treatment].
PMID- 25138404
TI - [Citation analysis of research articles from Norwegian health enterprises, 2005
2011].
AB - BACKGROUND: The citation frequency of a publication is often interpreted as an
expression of its scientific impact. Previous citation analyses of Norwegian
medical research have either focused on universities and university hospitals or
on subject areas at the national level. Such analyses have paid little attention
to other health enterprises, despite a strong increase in their research activity
during the last decade. MATERIAL AND METHOD: For all health enterprises with more
than 25 publications in the Web of Science during the period 2005-2011 we have
calculated field normalized citation indexes at the institution and subject
levels. RESULTS: On the whole, research undertaken by the health enterprises is
frequently cited, and some medium-sized health enterprises stand out in terms of
their high average citation indexes: Helse Stavanger Health Enterprise,
Diakonhjemmet Hospital and Helse Nord-Trondelag Health Enterprise, although Oslo
University Hospital Health Enterprise and Helse Bergen Health Enterprise account
for more than half of the most cited articles. INTERPRETATION: In citation
analyses at the aggregated level, highly and infrequently cited research
groups/departments may balance each other. This appears to be the case in the
largest health enterprises. Some medium-sized health enterprises that have a more
concentrated research portfolio will thus accumulate higher average citation
indexes than the largest university hospitals.
PMID- 25138405
TI - [Two migrated intrauterine devices].
PMID- 25138406
TI - [A man in his forties with swelling in both orbits].
AB - Erdheim-Chester disease. A multi-disiplinary challenge. The histiocytoses are a
diverse, but rare group of disorders with symptoms affecting many organs, varying
from self-limiting, localised lesions to disseminated multi-organ disease. The
diagnostic challenges are illustrated and discussed in the following case. CASE
REPORT: A man in his forties was admitted to hospital due to pain in his right
eye and visual disturbances. MRI imaging detected a mass in his right orbit and a
minor mass in his left orbit. The histological results of the mass in his right
orbit revealed an inflammatory process with lymphocytes and macrophages and no
sign of vasculitis, infection or malignancy. The diagnosis pseudotumor orbita was
made and treatment with corticosteroids was initiated. He did not respond to
corticosteroids or radiotherapy and increasing symptoms necessitated
rehospitalisation. Further tests disclosed a multisystem disease which affected
the aorta, skeleton, lung, heart and kidney. The biopsy was reconsidered and the
disease was classified as a histiocytosis with CD68 positive and CD1a negative
cells. The diagnosis Erdheim-Chester was given, about 14 months after the initial
hospitalisation. Treatment with interferon alpha was started.
PMID- 25138407
TI - [Goals and means in medical education].
PMID- 25138408
TI - [Hidden learning within the medical education--what books do not tell].
PMID- 25138409
TI - [Professionalism does not come by itself].
PMID- 25138410
TI - Lack of earthing in Cambodia.
PMID- 25138411
TI - [Watchdog in medical records].
PMID- 25138423
TI - Colloid cysts: endoscopic or microsurgical resection?
PMID- 25138424
TI - Perspectives: has intraoperative near infrared indocyanine green video
angiography replaced formal angiography in aneurysm surgery?
PMID- 25138426
TI - Does a test impact on a patient's life many years from now?
PMID- 25138425
TI - Haploidentical hematopoietic stem cell transplantation in adults with
Philadelphia-negative acute lymphoblastic leukemia: no difference in the high-
and low-risk groups.
AB - Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective
post-consolidation therapy and curative option for adult patients with
Philadelphia chromosome-negative (Ph-negative) acute lymphoblastic leukemia (ALL)
in first complete remission (CR1). A human leukocyte antigen (HLA)-haploidentical
related donor (haplo-RD) is one of the most important alternative sources for
those without HLA-identical sibling donor (ISD). The present study aimed to
evaluate the outcomes of haploidentical hematopoietic stem cell transplantation
(haplo-HSCT) in adult Ph-negative ALL CR1 patients (n = 183). We produced an
unmanipulated haplo-HSCT protocol including granulocyte colony stimulating factor
(G-CSF) for all donors, intensive immune suppression, anti-thymocyte globulin,
and combination of G-CSF-primed bone marrow harvest and G-CSF-mobilized
peripheral blood stem cells harvest as the source of stem cell grafts. The median
age for high-risk versus low-risk groups were 29 versus 23 years. Three-year
incidences of relapse mortality and nonrelapse mortality for high-risk versus low
risk groups were 7.1% versus 11.1% (p = 0.498) and 18.0% versus 16.2% (p =
0.717), respectively. Three-year probabilities of disease-free survival and
overall survival for high-risk versus low-risk groups were 67.6% versus 68.2% (p
= 0.896) and 74.9% versus 72.7% (p = 0.981), respectively. Multivariate analysis
showed that limited cGVHD and a lower pre-HSCT comorbidity burden were associated
with better outcomes. In summary, comparable outcomes were observed among high-
and low-risk Ph-negative ALL CR1 patients after haplo-HSCT. Haplo-RD could be
considered for adults with Ph-negative ALL in CR1 as an important alternative
source of donors in cases when no ISD is available.
PMID- 25138428
TI - A hospital-based survey on food allergy in the population of Kolkata, India.
AB - BACKGROUND: Food allergy is increasing worldwide, and Asian countries are not the
exception. Still, ample data are lacking in India. We conducted a cross-sectional
study in a metropolis of Eastern India to record the presence of food allergy
among the local population. METHODS: The prevalence of food allergy was
investigated among patients reporting to The Institute of Child Health and
Mediland Diagnostics in Kolkata, India. A total of 5,161 patients were subdivided
into 3 age groups and surveyed accordingly. The evaluation was conducted via a
questionnaire and a skin prick test. RESULTS: Among the 5,161 patients tested,
4,160 showed a positive response to one or more food items. Banana (32%), brinjal
(29%), wheat (22%), and egg (23%) were found to be dominant allergens. Sixty
three percent of patients with a family history of allergy showed either a sudden
or an insidious mode of onset, whereas the remaining 37% suffered insidious
allergic symptoms with no record of a family history of allergy. Skin rashes,
cough, and sneezing were the major symptoms observed. Patients in the age group
of 15-40 years were the most susceptible. CONCLUSION: It has been observed that
certain specific foods consumed in specific regions cause allergies that are
unique to their respective populations. In the present study, the most commonly
consumed foods in the studied area, e.g. banana, brinjal, wheat, and egg, had
severe effects on the local population. Complementary studies in other countries
as well as in other parts of India will allow us to gain further insight into
this fact. Some other influencing factors were found to be genetics, cultural
habits, and occupation. Avoidance of the allergy-causing food is the best way to
deal with food allergy.
PMID- 25138427
TI - Molecular imaging to predict ventricular arrhythmia in heart failure.
AB - Ventricular tachycardia (VT) is a major cause of sudden cardiac death (SCD) in
patients with heart failure (HF). Left ventricular ejection fraction (LVEF) and
heart failure class according to the New York Heart association (NYHA) are in
most common use to identify patients that may benefit from implantable
cardioverter defibrillator (ICD) therapy. But during 3 years of follow up only
35% of patients receive appropriate ICD action. Therefore, there is a continued
need for refinement of selection criteria for ICD implantation. In this regard,
molecular imaging of the autonomic nervous system, which plays a central role in
HF progression and cardiac electro-mechanical regulation, can make a substantial
contribution. This article reviews the currently available literature concerning
the value of molecular neuronal cardiac imaging for prediction of ventricular
arrhythmias in HF patients.
PMID- 25138429
TI - Poor dietary diversity and low nutrient density of the complementary diet for 6-
to 24-month-old children in urban and rural KwaZulu-Natal, South Africa.
AB - Infants and toddlers have high nutritional requirements relative to body size but
consume small amounts of food and therefore need nutrient-dense complementary
foods. A cross-sectional study included children aged 6-24 months, stratified in
three age categories (6-11 months, 12-17 months and 18-24 months) and randomly
selected from an urban (n = 158) and a rural (n = 158) area, both of low socio
economic status, in the KwaZulu-Natal Province of South Africa. Dietary diversity
and nutrient density of the complementary diet (excluding breast milk and formula
milk) based on a repeated 24-h dietary recall was assessed. For breastfeeding
children, nutrient density of the complementary diet was adequate for protein,
vitamin A and vitamin C; and inadequate for 100% of children for zinc, for >80%
of children for calcium, iron and niacin; and between 60% and 80% of children for
vitamin B6 and riboflavin. Urban/rural differences in density for animal and
plant protein, cholesterol and fibre occurred in 18-24-month-old children. Fewer
than 25% of children consumed >=4 food groups, with no urban/rural differences.
Higher dietary diversity was associated with higher nutrient density for protein
and several of the micronutrients including calcium, iron and zinc. The poor
nutrient density for key micronutrients can probably be ascribed to lack of
dietary variety, and little impact of mandatory fortification of maize meal/wheat
flour on infants/toddlers' diet. Targeted strategies are needed to enable mothers
to feed their children a more varied diet.
PMID- 25138430
TI - Is the incidence of malignancy increased in patients with sarcoidosis? A
systematic review and meta-analysis.
AB - A possible causal relationship between sarcoidosis and malignancy has been the
subject of debates for decades. To better understand this association, we
conducted a systematic review and meta-analysis of cohort studies that reported
relative risk, hazard ratio or standardized incidence ratio with 95% confidence
interval (CI) comparing the incidence of malignancy in patients with sarcoidosis
versus non-sarcoidosis participants. Pooled risk ratios (RR) and 95% CI were
calculated using a random-effect, generic inverse variance methodology. Five
studies were identified and included in our data analyses. The pooled RR of
malignancy in patients with sarcoidosis was 1.21 (95% CI: 1.04-1.40). However,
when we performed a sensitivity analysis that included only studies that compared
the incidence of malignancy after the first year of the diagnosis of sarcoidosis
with the incidence of malignancy after the first year of index date for non
sarcoidosis controls, the pooled risk ratio decreased and did not reach
statistical significance (RR 1.13, 95% CI: 0.97-1.32). Furthermore, analysis for
publication bias has suggested that publication bias in favour of positive
studies may be present. In conclusion, after accounting for possible detection
bias and publication bias, there does not appear be a significant association
between sarcoidosis and malignancy.
PMID- 25138431
TI - A review of the indirect protection of younger children and the elderly through a
mass influenza vaccination program in Japan.
AB - In the past, Japan's strategy for controlling influenza was to vaccinate
schoolchildren based on the theory that this could reduce influenza epidemics in
the community, and a special program to vaccinate schoolchildren against
influenza was begun in 1962. However, the program was discontinued in 1994
because of lack of evidence that it had limited the spread of influenza in the
community. In 2001, it was reported that a clear decrease in excess mortality had
coincided with the timing of the schoolchild vaccination program. This decrease
could have potentially occurred because elderly people were protected by herd
immunity generated by the program. Moreover, the program protected the younger
siblings of schoolchildren against influenza-associated encephalopathy. Finally,
the program was effective in reducing the number of class cancellations and
absenteeism from school. During the period when the program was in effect,
Japanese schoolchildren served as a barrier against influenza in the community.
PMID- 25138432
TI - Variation in plant defences among populations of a range-expanding plant:
consequences for trophic interactions.
AB - Although plant-herbivore-enemy interactions have been studied extensively in
cross-continental plant invasions, little is known about intra-continental range
expanders, despite their rapid spread globally. Using an ecological and
metabolomics approach, we compared the insect performance of a generalist and
specialist herbivore and a parasitoid, as well as plant defence traits, among
native, exotic invasive and exotic non-invasive populations of the Turkish
rocket, Bunias orientalis, a range-expanding species across parts of Eurasia. In
the glasshouse, the generalist herbivore, Mamestra brassicae, and its parasitoid,
Microplitis mediator, performed better on non-native than on native plant
populations. Insect performance did not differ between the two non-native
origins. By contrast, the specialist herbivore, Pieris brassicae, developed
poorly on all populations. Differences in trichome densities and in the
metabolome, particularly in the family-specific secondary metabolites (i.e.
glucosinolates), may explain population-related variation in the performance of
the generalist herbivore and its parasitoid. Total glucosinolate concentrations
were significantly induced by herbivory, particularly in native populations.
Native populations of B. orientalis are generally better defended than non-native
populations. The role of insect herbivores and dietary specialization as a
selection force on defence traits in the range-expanding B. orientalis is
discussed.
PMID- 25138433
TI - Overestimation of body size in eating disorders and its association to body
related avoidance behavior.
AB - Body-related avoidance behavior, e.g., not looking in the mirror, is a common
feature of eating disorders. It is assumed that it leads to insufficient feedback
concerning one's own real body form and might thus contribute to distorted mental
representation of one's own body. However, this assumption still lacks empirical
foundation. Therefore, the aim of the present study was to examine the
relationship between misperception of one's own body and body-related avoidance
behavior in N = 78 female patients with Bulimia nervosa and eating disorder not
otherwise specified. Body-size misperception was assessed using a digital photo
distortion technique based on an individual picture of each participant which was
taken in a standardized suit. In a regression analysis with body-related
avoidance behavior, body mass index and weight and shape concerns as predictors,
only body-related avoidance behavior significantly contributed to the explanation
of body-size overestimation. This result supports the theoretical assumption that
body-related avoidance behavior makes body-size overestimation more likely.
PMID- 25138434
TI - Quercetin induces mitochondrial-derived apoptosis via reactive oxygen species
mediated ERK activation in HL-60 leukemia cells and xenograft.
AB - Quercetin is a plant-derived bioflavonoid that was recently shown to have
multiple anticancer activities in various solid tumors. Here, novel molecular
mechanisms through which quercetin exerts its anticancer effects in acute myeloid
leukemia (AML) cells were investigated. Results from Western blot and flow
cytometric assays revealed that quercetin significantly induced caspase-8,
caspase-9, and caspase-3 activation, poly ADP-ribose polymerase (PARP) cleavage,
and mitochondrial membrane depolarization in HL-60 AML cells. The induction of
PARP cleavage by quercetin was also observed in other AML cell lines: THP-1, MV4
11, and U937. Moreover, treatment of HL-60 cells with quercetin induced sustained
activation of extracellular signal-regulated kinase (ERK), and inhibition of ERK
by an ERK inhibitor significantly abolished quercetin-induced cell apoptosis.
MitoSOX red and 2',7'-dichlorofluorescin fluorescence, respectively, showed that
mitochondrial superoxide and intracellular peroxide levels were higher in
quercetin-treated HL-60 cells compared with the control group. Moreover, both N
acetylcysteine and the superoxide dismutase mimetic, MnTBAP, reversed quercetin
induced intracellular reactive oxygen species production, ERK activation, and
subsequent cell death. The in vivo xenograft mice experiments revealed that
quercetin significantly reduced tumor growth through inducing intratumoral
oxidative stress while activating the ERK pathway and subsequent cell apoptosis
in mice with HL-60 tumor xenografts. In conclusions, our results indicated that
quercetin induced cell death of HL-60 cells in vitro and in vivo through
induction of intracellular oxidative stress following activation of an ERK
mediated apoptosis pathway.
PMID- 25138436
TI - Gadolinium- or iodine-based contrast media: which choice?
PMID- 25138435
TI - Role of two types of angiotensin II receptors in colorectal carcinoma
progression.
AB - Angiotensin II (Ang-II) is a bioactive peptide associated closely with the
progression and metastasis of colorectal cancer (CRC). We examined the expression
and role of 2 Ang-II receptor types in 20 cases of CRC. Ang-II type 1 receptor
(AT1R) protein was localized to the plasma membrane, whereas Ang-II type 2
receptor (AT2R) protein was localized to the nuclei. AT1R expression showed a
direct correlation with tumor stage and liver metastasis, whereas AT2R expression
showed an inverse correlation. A knockdown study of the AT1R or AT2R with Ang-II
treatment was performed to reveal their individual roles in a mouse rectal cell
line CMT93, which expresses both Ang-II receptor types. AT2R knockdown showed
that the AT1R was associated with tumor growth, survival, invasion and VEGF-A
secretion in CMT93 cells in a dose-dependent manner. In contrast, AT1R knockdown
showed that the AT2R was associated with increased VEGF-A secretion at low Ang-II
concentrations, whereas high concentrations of Ang-II inhibited tumor growth,
survival, invasion and VEGF-A secretion. Thus, the AT1R showed a monophasic
protumoral effect, while the AT2R showed a biphasic amphitumoral effect. Our
findings suggest that a high angiotensinogen condition in the liver might evoke
the antitumoral role of the AT2R in CRC cells.
PMID- 25138438
TI - Commercially available mobile phone headache diary apps: a systematic review.
AB - BACKGROUND: Headache diaries are often used by headache sufferers to self-monitor
headaches. With advances in mobile technology, mobile electronic diary apps are
becoming increasingly common. OBJECTIVE: This review aims to identify and
evaluate all commercially available mobile headache diary apps for the two most
popular mobile phone platforms, iOS and Android. METHODS: The authors developed a
priori a set of 7 criteria that define an ideal headache diary app intended to
help headache sufferers better understand and manage their headaches, while
providing relevant data to health professionals. The app criteria were intended
as minimum requirements for an acceptable headache diary app that could be
prescribed by health care professionals. Each app was evaluated and scored
against each criterion. RESULTS: Of the 38 apps identified, none of the apps met
all 7 app criteria. The 3 highest scoring apps, meeting 5 of the app criteria,
were iHeadache (developed by Better QOL), ecoHeadache (developed by
ecoTouchMedia), and Headache Diary Pro (developed by Froggyware). Only 18% of the
apps were created with scientific or clinical headache expertise and none of the
apps reported on psychometric properties. CONCLUSIONS: Despite the growing market
and demand, there is a concerning lack of scientific expertise and evidence base
associated with headache diary apps.
PMID- 25138437
TI - OsABCG15 encodes a membrane protein that plays an important role in anther
cuticle and pollen exine formation in rice.
AB - KEY MESSAGE: An ABC transporter gene ( OsABCG15 ) was proven to be involved in
pollen development in rice. The corresponding protein was localized on the plasma
membrane using subcellular localization. Wax, cutin, and sporopollenin are
important for normal development of the anther cuticle and pollen exine,
respectively. Their lipid soluble precursors, which are produced in the tapetum,
are then secreted and transferred to the anther and microspore surface for
polymerization. However, little is known about the mechanisms underlying the
transport of these precursors. Here, we identified and characterized a member of
the G subfamily of ATP-binding cassette (ABC) transporters, OsABCG15, which is
required for the secretion of these lipid-soluble precursors in rice. Using map
based cloning, we found a spontaneous A-to-C transition in the fourth exon of
OsABCG15 that caused an amino acid substitution of Thr-to-Pro in the predicted
ATP-binding domain of the protein sequence. This osabcg15 mutant failed to
produce any viable pollen and was completely male sterile. Histological analysis
indicated that osabcg15 exhibited an undeveloped anther cuticle, enlarged middle
layer, abnormal Ubisch body development, tapetum degeneration with a falling
apart style, and collapsed pollen grains without detectable exine. OsABCG15 was
expressed preferentially in the tapetum, and the fused GFP-OsABCG15 protein was
localized to the plasma membrane. Our results suggested that OsABCG15 played an
essential role in the formation of the rice anther cuticle and pollen exine. This
role may include the secretion of the lipid precursors from the tapetum to
facilitate the transfer of precursors to the surface of the anther epidermis as
well as to microspores.
PMID- 25138439
TI - Tethering metal ions to photocatalyst particulate surfaces by bifunctional
molecular linkers for efficient hydrogen evolution.
AB - A simple and versatile method for the preparation of photocatalyst particulates
modified with effective cocatalysts is presented; the method involves the
sequential soaking of photocatalyst particulates in solutions containing
bifunctional organic linkers and metal ions. The modification of the particulate
surfaces is a universal and reproducible method because the molecular linkers
utilize strong covalent bonds, which in turn result in modified monolayer with a
small but controlled quantity of metals. The photocatalysis results indicated
that the CdS with likely photochemically reduced Pd and Ni, which were initially
immobilized via ethanedithiol (EDT) as a linker, were highly efficient for
photocatalytic hydrogen evolution from Na2S-Na2SO3-containing aqueous solutions.
The method developed in this study opens a new synthesis route for the
preparation of effective photocatalysts with various combinations of bifunctional
linkers, metals, and photocatalyst particulate materials.
PMID- 25138440
TI - Pathologic changes associated with suspected hypovitaminosis A in amphibians
under managed care.
AB - Vitamin A deficiency is a recently recognized nutritional disease in amphibians
fed insect-based diets. The classic pathologic lesion that has been associated
with hypovitaminosis A in amphibians is squamous metaplasia of the lingual and
oral mucosa. In an attempt to further characterize the range of lesions that may
be associated with vitamin A deficiency, we reviewed archived amphibian necropsy
reports from three facilities. As previously reported, the tongue was the most
commonly affected site in animals presenting with squamous metaplasia. However,
metaplastic changes were also observed in a variety of locations that included
the oral cavity, nasal cavity, pharynx, esophagus, stomach, cloaca, skin, urinary
bladder, ureter, and reproductive tract. In addition, species and age-specific
differences were noted in the development of squamous metaplasia. This review
highlights the need to establish standardized guidelines for optimal postmortem
tissue sampling of amphibians in order to maximize the accurate diagnosis of
pathologic lesions that may be associated with hypovitaminosis A. Zoo Biol.
33:508-515, 2014. (c) 2014 Wiley Periodicals Inc.
PMID- 25138442
TI - Multifunctional Ag-decorated porous TiO2 nanofibers in dye-sensitized solar
cells: efficient light harvesting, light scattering, and electrolyte contact.
AB - Designing the photoanode structure in dye-sensitized solar cells (DSSCs) is vital
to realizing enhanced power conversion efficiency (PCE). Herein, novel
multifunctional silver-decorated porous titanium dioxide nanofibers (Ag/pTiO2
NFs) made by simple electrospinning, etching, and chemical reduction processes
are introduced. The Ag/pTiO2 NFs with a high surface area of 163 m(2) g(-1)
provided sufficient dye adsorption for light harvesting. Moreover, the
approximately 200 nm diameter and rough surface of the Ag/pTiO2 NFs offered
enough light scattering, and the enlarged interpores among the NFs in the
photoanode also permitted electrolyte circulation. Ag nanoparticles (NPs) were
well dispersed on the surface of the TiO2 NFs, which prevented aggregation of the
Ag NPs after calcination. Furthermore, a localized surface plasmon resonance
effect by the Ag NPs served to increase the light absorption at visible
wavelengths. The surface area and amount of Ag NPs was optimized. The PCE of
pTiO2 NF-based DSSCs was 27 % higher (from 6.2 to 7.9 %) than for pure TiO2 NFs,
whereas the PCE of Ag/pTiO2 NF-based DSSCs increased by about 12 % (from 7.9 to
8.8 %). Thus, the PCE of the multifunctional pTiO2 NFs was improved by 42 %, that
is, from 6.2 to 8.8 %.
PMID- 25138441
TI - Exogenous salicylic acid activates two signaling arms of the unfolded protein
response in Arabidopsis.
AB - The unfolded protein response (UPR) is a highly conserved cellular response that
prevents abnormal maturation of proteins in the endoplasmic reticulum (ER). The
expression of genes encoding ER chaperones is induced during the UPR. In the
Arabidopsis UPR, two membrane-bound transcription factors, bZIP60 and bZIP28,
activate the expression of those genes. bZIP60 is regulated by unconventional
cytoplasmic splicing catalyzed by inositol requiring enzyme 1 (IRE1), which is
located in the ER membrane. bZIP28 is regulated by intramembrane proteolysis.
Pathogen infection and salicylic acid (SA) have been reported to induce the
expression of some UPR genes. Here, we show that UPR genes including BiP3, a
marker gene of the Arabidopsis UPR, are induced by exogenous SA treatment and
activation of bZIP60 in an IRE1-dependent manner. The induction of gene
expression and activation of bZIP60 were independent of NPR1 and HsfB1 under
these experimental conditions. We generated antibodies to detect the proteolytic
products of bZIP28 after SA treatment. An assay using these antibodies showed
that SA activated bZIP28, as well as activating bZIP60 through IRE1. Together,
these results show that exogenous SA treatment activates two signaling arms of
the Arabidopsis UPR. We propose a possible mechanism of activation of the UPR
machinery by SA.
PMID- 25138443
TI - Comment on the paper by Kamel et al. Entitled 'Primary cytomegalovirus infection
in pregnant Egyptian women confirmed by cytomegalovirus IgG avidity testing'.
PMID- 25138445
TI - An iron(II) complex featuring kappa(3) and labile kappa(2)-bound PNP pincer
ligands - striking differences between CH2 and NH spacers.
AB - Treatment of anhydrous FeCl2 with 2 equiv. of the pincer ligand PNP-Ph afforded
the diamagnetic cationic octahedral complex [Fe(kappa(3)-P,N,P-PNP)(kappa(2)-P,N
PNP)Cl](+) featuring a kappa(2)-P,N-bound PNP ligand. Preliminary reactivity
studies revealed that the kappa(2)-P,N-bound PNP ligand is labile reacting with
CO to afford trans-[Fe(PNP-Ph)(CO)2Cl](+).
PMID- 25138444
TI - Development and evaluation of a new survey instrument to measure the quality of
colorectal cancer screening decisions.
AB - BACKGROUND: Guidelines for colorectal cancer screening recommend that patients be
informed about options and be able to select preferred method of screening;
however, there are no existing measures available to assess whether this happens.
METHODS: Colorectal Cancer Screening Decision Quality Instrument (CRC-DQI)
includes knowledge items and patients' goals and concerns. Items were generated
through literature review and qualitative work with patients and providers.
Hypotheses relating to the acceptability, feasibility, discriminant validity and
retest reliability of the survey were examined using data from three studies: (1)
2X2 randomized study of participants recruited online, (2) cross-sectional sample
of patients recruited in community health clinics, and (3) cross-sectional sample
of providers recruited from American Medical Association Master file. RESULTS:
338 participants were recruited online, 94 participants were recruited from
community health centers, and 115 physicians were recruited. The CRC-DQI was
feasible and acceptable with low missing data and high response rates for both
online and paper-based administrations. The knowledge score was able to
discriminate between those who had seen a decision aid or not (84% vs. 64%, p <
0.001) and between providers, online patients and clinic patients (89% vs. 74%
vs. 41%, p < 0.001 for all comparisons). The knowledge score and most of the
goals had adequate retest reliability. About half of the participants received a
test that matched their goals (47% and 51% in online and clinic samples
respectively). Many respondents who had never been screened had goals that
indicated a preference for colonoscopy. A minority of respondents in the online
(21%) and in clinic (2%) samples were both well informed and received a test that
matched their goals. CONCLUSIONS: The CRC-DQI demonstrated good psychometric
properties in diverse samples, and across different modes of administration. Few
respondents made high quality decisions about colon cancer screening.
PMID- 25138463
TI - Overproduction of geranylgeraniol in Coprinopsis cinerea by the expression of
geranylgeranyl diphosphate synthase gene.
AB - (E, E, E)-Geranylgeraniol (GGOH) is a valuable ingredient of many perfumes and a
valuable precursor for synthesizing pharmaceuticals. In an attempt to increase
the GGOH concentration in Coprinopsis cinerea, we demonstrated that the
expression of geranylgeranyl diphosphate synthase (ggpps) gene isolated from
Taxus x media could promote GGOH production. Furthermore, the concentrations of
squalene and ergosterol were measured in the engineered strains. Expectedly,
significant decreases of squalene and ergosterol levels were observed in those
strains transformed with ggpps gene. This could be explained by the partial
redirection of metabolic flux from squalene to GGOH, whose biosynthesis competes
for the same precursor with squalene. This work suggested that the expression of
ggpps in higher fungi was an effective method for bio-production of GGOH.
PMID- 25138464
TI - Pathology of gastric lesions in donkeys: A preliminary study.
AB - REASONS FOR PERFORMING STUDY: Donkeys (Equus africanus asinus) are important
working animals, particularly in countries where the majority of the population
lives below the poverty line. Gastric ulceration has been shown to be common in
British donkeys but donkeys from other parts of the world have not been as
extensively researched. OBJECTIVES: This study was performed as a preliminary
overview of the severity and distribution of gastric lesions in mature donkeys
and to document which parasites were present. STUDY DESIGN: Descriptive study of
pathological findings. METHODS: Stomachs of 35 mature draught donkeys were
examined grossly and histopathology samples taken from 5 regions of the gastric
mucosa. RESULTS: Gross examination revealed hyperaemia, oedema, erosions and
ulcers in addition to parasitic lesions. Histopathological examination revealed
hyperkeratosis, acanthosis, vacuolar degeneration of stratified squamous cells,
gastritis, erosions, ulcerations, scarring, hyperactivity of mucus glands,
periglandular fibroplasia and parasitic granulomes with infestation by
Gasterophilus spp. larvae, Habronema spp. and Draschia megastoma. CONCLUSIONS: In
donkeys, ulceration of the nonglandular regions of the stomach is more prominent
than the glandular regions and parasitic infestations were frequent.
PMID- 25138465
TI - Sonographic appearance of thyroid glands in patients treated with intensity
modulated radiotherapy or conventional radiotherapy for nasopharyngeal carcinoma.
AB - BACKGROUND: This study aimed to investigate the sonographic appearances of the
thyroid glands in nasopharyngeal carcinoma (NPC) patients whose cervical lymph
nodes were treated with conventional radiotherapy (RT) or intensity-modulated
radiotherapy (IMRT). The post-RT sonographic appearances of the thyroid glands in
NPC patients were also correlated with the thyroid function. METHODS: One hundred
and three NPC patients who had completed RT of cervical lymph nodes using the
anterior cervical field, 30 NPC patients who had completed RT of cervical lymph
nodes using IMRT, and 61 healthy subjects were included in the study. Thyroid
glands were sonographically assessed for their size, echogenicity, vascularity,
and internal architecture. Thyroid function tests were also performed on each
subject. RESULTS: In comparison with the patients with abnormal thyroid function,
the thyroid glands of the patients with normal thyroid function tended to be
homogeneous and to have greater volume and echogenicity index (p < 0.05).
Compared with those of the healthy subjects, the thyroid glands of patients
previously treated with IMRT and those treated with the anterior cervical field
showed significantly lower thyroid volume, lower incidence and number of nodules,
and higher vascularity index (p < 0.05). CONCLUSIONS: The patient's history of
previous RT should be taken into consideration in the sonographic examination of
the thyroid gland post-RT. (c) 2014 Wiley Periodicals, Inc. J Clin Ultrasound
43:210-223, 2015.
PMID- 25138466
TI - Protonation induced shifting of electron-accepting centers in intramolecular
charge transfer chromophores: a theoretical study.
AB - A new series of chameleonic molecules containing azulene and benzothiadiazole
(BT) were designed and synthesized. In the neutral state, BT functions as an
electron accepting center, while upon protonation, the electron accepting center
shifts to azulene moieties, leading to a remarkable extension of absorption to
the NIR region, i.e. up to 2.5 MUm. The interchange between donor and acceptor
characters upon protonation was confirmed by UV-vis-NIR spectral studies and
supported by DFT calculations. Furthermore, the HOMO-LUMO level of ICT
chromophores could be finely tailored by a different arrangement of azulenes and
BTs in the molecules. The interchange between donor and acceptor characters upon
protonation provides an alternative yet effective approach to fine tune optical
and electronic properties of NIR chromophores.
PMID- 25138468
TI - Converting molecular monolayers into functional membranes.
AB - Carbon nanomembranes are constructed from monolayers of molecular amphiphiles
assembled on a water surface. The floating molecular film is cross-linked to form
a mechanically stable nanomembrane. By varying the type of molecules, the surface
area, and the exposure condition, the membrane's stiffness, thickness, and
permeability can be tailored.
PMID- 25138469
TI - Systematic review of literature of cemented femoral components: what is the
durability at minimum 20 years followup?
AB - BACKGROUND: Cemented femoral total hip arthroplasty may be one of the most
successful surgical interventions of all time. However, although results are very
encouraging over the early to mid-term followup, relatively few studies have
analyzed the durability of these implants beyond 20 years followup. To evaluate
the performance of contemporary implants, it is important to understand how
previous implants perform at 20 or more years of followup; one way to do this is
to aggregate the available data in the form of a systematic review.
QUESTIONS/PURPOSES: (1) How durable is cemented femoral fixation in the long term
(minimum 20-year followup) with respect to aseptic loosening? (2) Is the
durability of cemented femoral fixation dependent on age of the patient? (3) Are
the long-term results of the cemented femoral fixation dependent on any
identifiable characteristics of the prosthesis such as surface finish? METHODS: A
systematic review was performed to identify long-term studies of cemented femoral
components. After application of inclusion and exclusion criteria to 1228
articles found with a search in PubMed and EMBASE, 17 studies with a minimum of
20-year followup on cemented femoral components were thoroughly analyzed in an
attempt to answer the questions of this review. The quality of the studies
reviewed was assessed with the Methodological Index for Nonrandomized Studies
(MINORS) instrument. All studies were case series and cohort sizes ranged from
110 to 2000 hips for patients older than 50 years of age and 41 to 93 hips for
patients younger than 50 years at the time of surgery. RESULTS: Among the six
case series performed in patients older than 50 years of age, survivorship for
aseptic loosening of the femoral component ranged from 86% to 98% at 20 years
followup. There were no obvious differences for younger patients when analyzing
the five studies in patients younger than age 50 years in which survivorship free
from aseptic loosening for these studies ranged from 77% at 20 years in one study
and 68% to 94% at 25 years in the other studies. Although data pooling could not
be performed because of heterogeneity of the studies included here, it appeared
that stems with a rougher surface finish did not perform as well as polished
stems; survivorship of stems with rougher surface finishes varied between 86% and
87%, whereas those with smoother finishes ranged between 93.5% and 98% at 20
years. CONCLUSIONS: Excellent long-term fixation in both older and younger
patients can be obtained with cemented, polished femoral stems. These results
provide material for comparison with procedures performed with newer cementing
techniques and newer designs, both cemented and cementless, at this extended
duration of followup.
PMID- 25138470
TI - CORR Insights(r): What sports activity levels are achieved in patients with
modular tumor endoprostheses of osteosarcoma about the knee?
PMID- 25138471
TI - Are Harris hip scores and gait mechanics related before and after THA?
AB - BACKGROUND: Discordance between subjective and objective functional measures
hinders the development of new ways to improve THA outcomes. QUESTIONS/PURPOSES:
We asked if (1) any kinematic or kinetic gait variables are correlated with
preoperative Harris hip scores (HHS), (2) any kinematic or kinetic gait variables
are correlated with postoperative HHS, and (3) pre- to postoperative changes in
any kinematic or kinetic gait variables are associated with the change in HHS?
METHODS: For this retrospective study, an institutional review board-approved
data repository that included all individuals who participated in motion analysis
research studies was used to identify subjects evaluated before (n=161) and at
least 6 months after primary unilateral THA (n=156). Selected kinematic (sagittal
plane dynamic hip ROM and kinetic (peak external moments about the hip in the
sagittal, frontal, and transverse planes) gait variables were collected at
subjects' self-selected normal walking speeds. We used first-order partial
correlations to identify relationships between HHS and gait variables,
controlling for the influence of speed. RESULTS: Preoperative HHS correlated with
hip ROM (R|speed=0.260; p<0.001) and the peak extension moment (R|speed=0.164;
p=0.038), postoperative HHS correlated with the peak internal rotation moment
(R|speed=0.178; p=0.034), and change in HHS correlated with change in hip ROM
(R|speed=0.288; p=0.001) and peak external rotation moment (R|speed=0.291;
p=0.002). Similar associations were seen when the HHS pain and function were
analyzed separately. CONCLUSIONS: This study identified relationships between a
common clinical outcome measure and specific, modifiable gait adaptations that
can persist after THA-ROM and transverse plane gait moments. Addressing these
aspects of gait dysfunction through focused rehabilitation could be a new
strategy for improving clinical outcomes. Prospective studies are needed to
evaluate this concept. LEVEL OF EVIDENCE: Level III, diagnostic study. See the
Instructions for Authors for a complete description of levels of evidence.
PMID- 25138472
TI - What is the effect of advanced age and comorbidity on postoperative morbidity and
mortality after musculoskeletal tumor surgery?
AB - BACKGROUND: Although the elderly population is increasing rapidly, little
information is available regarding how the risk of postoperative mortality and
morbidity increases when combined with age and comorbidity burden in patients
undergoing musculoskeletal tumor surgery. QUESTIONS/PURPOSES: We evaluated the
effect of age and comorbidity burden on the (1) postoperative complication rate
and (2) in-hospital mortality rate after musculoskeletal tumor surgery. METHODS:
We identified 5716 patients undergoing musculoskeletal tumor surgery during 2007
to 2012 using a Japanese national inpatient database. Logistic regression
analyses were performed to examine the relationships of various factors with the
rates of mortality and morbidity. RESULTS: The postoperative complication rate
(6.7%) was associated with male sex (p = 0.033), age 80 years or older (p =
0.001), tumor located in the lower extremity (p = 0.001) or trunk (p = 0.019),
Charlson Comorbidity Index of 4 or greater (p < 0.001), blood transfusion (p <
0.001), and duration of anesthesia of 240 minutes or longer (p < 0.001). The in
hospital mortality (0.8%) was related to the Charlson Comorbidity Index of 4 or
greater (p < 0.001), blood transfusion (p < 0.001), and high hospital volume (p =
0.016). The morbidity (21.6%; OR, 3.29; p < 0.001) and mortality (4.1%; OR, 5.95;
p < 0.001) in patients 80 years or older with a Charlson Comorbidity Index of 4
or greater was increased three and six times, respectively, compared with
patients 64 years or younger with no comorbidity. CONCLUSIONS: We found that age
and comorbidity burden together greatly increased the risk of morbidity and
mortality. Our study showed quantitative evidence that will assist physicians in
assessing perioperative risk accurately and provide a more informative
explanation to elderly patients undergoing musculoskeletal tumor surgery. LEVEL
OF EVIDENCE: Level IV, prognostic study. See the Instructions for Authors for a
complete description of levels of evidence.
PMID- 25138473
TI - Do patients with insulin-dependent and noninsulin-dependent diabetes have
different risks for complications after arthroplasty?
AB - BACKGROUND: Patients with diabetes are known to be at greater risk for
complications after arthroplasty than are patients without diabetes. However, we
do not know whether there are important differences in the risk of perioperative
complications between patients with diabetes who are insulin-dependent (Type 1 or
2) and those who are not insulin-dependent. QUESTIONS/PURPOSES: The purpose of
our study was to compare (1) medical complications (including death), (2)
surgical complications, and (3) readmissions within 30 days between patients with
insulin-dependent and noninsulin-dependent diabetes, and with patients who do not
have diabetes. METHODS: A total of 43,299 patients undergoing THA or TKA between
2005 and 2011 were selected from the American College of Surgeon's National
Surgical Quality Improvement Program's (ACS-NSQIP(r)) database. Generalized
linear models were used to assess the relationship between diabetes status and
outcomes (no diabetes [n=36,574], insulin dependent [n=1552], and noninsulin
dependent [n=5173]). Multivariate models were established adjusting for
confounders including age, sex, race, BMI, smoking, steroid use, hypertension,
chronic obstructive pulmonary disease, and anesthesia type. Post hoc comparisons
between patient groups were made using a Bonferroni correction. RESULTS: Patients
who were insulin dependent had increased odds of experiencing a medical
complication (OR, 1.6; 95% CI, 1.2-2.0; p<0.001), as did patients who were
noninsulin dependent (OR, 1.2; 95% CI, 1.1-1.4; p<0.001). An increased likelihood
of 30-day mortality was found only for patients who were insulin dependent (OR,
3.74; 95% CI, 1.6-8.5; p=0.007). However, neither diabetic state was associated
with surgical complications. Finally, readmission was found to be independently
associated with insulin-dependent diabetes (OR, 1.6; 95% CI, 1.1-2.1; p=0.023).
CONCLUSIONS: Patients with insulin-dependent diabetes are most likely to have a
medical complication or be readmitted within 30 days after total joint
replacement. However, patients who are insulin dependent or noninsulin dependent
are no more likely than patients without diabetes to have a surgical
complication. Physicians and hospitals should keep these issues in mind when
counseling patients and generating risk-adjusted outcome reports. LEVEL OF
EVIDENCE: Level III, therapeutic study. See the Instructions for Authors for a
complete description of levels of evidence.
PMID- 25138474
TI - Buccal grafts for urethroplasty in pre-pubertal boys: what happens to the
neourethra after puberty?
AB - OBJECTIVE: Buccal mucosa grafts (BMG) are often used in complex urethral
reconstruction. Following pubertal endogenous androgen stimulation (EAS) in
prepubertal boys, there are concerns that the neourethra may not grow
proportionally to the phallus. To address the paucity of literature on the topic,
this article reports on data for post-pubertal follow up after pre-pubertal BMG
urethroplasties (BMGU). PATIENTS AND METHODS: Retrospective chart review of boys
who underwent staged BMGU before the age of 12 years at a single referral center
between 2000 and 2010 and who were followed up until after puberty. Demographic
information, initial meatal location, quality of graft before tubularization,
flow rate parameters (FRP) and complications were captured. RESULTS: Of the 137
patients who underwent staged BMGU during the study period, 10 satisfied the
inclusion criteria. Mean patient age at first stage BMGU was eight years (range
five to eleven years). The mean follow-up was 40.6 months (9-66 months). The
grafts were harvested from the cheek and lower lip in seven and three cases,
respectively. The mean interval between the first and second stage was 15.8
months (6-87 months). Complications included one urethro-cutaneous fistula and
two cases of glanular dehiscence. The final position of the meatus was glanular
in nine boys and coronal in one. Importantly, no recurrent ventral curvature (VC)
was found during the second stage BMGU or reported after puberty. All patients
demonstrated normal maximum flow after puberty (mean 25.7 ml/s). CONCLUSION:
Buccal mucosa grafts appear to grow proportionally to the phallus after pubertal
EAS. No recurrent VC or inadequate FRP were observed in this series. Despite the
small number of subjects, the results are reassuring and support continued use of
BMG in the pediatric pre-pubertal population.
PMID- 25138475
TI - Primary versus secondary ureteroscopy for pediatric ureteral stones.
AB - OBJECTIVE: To evaluate the outcome of primary versus secondary ureteroscopy for
pediatric ureteral stones. PATIENTS AND METHODS: A retrospective chart review
study that included 66 children aged less than 12 years, who were subdivided into
two groups: Group A, which included 42 children who had undergone primary
ureteroscopy without pre-stenting; and Group B, which included 24 children who
had undergone ureteroscopy after ureteric stenting. Kidneys, ureters and bladder
radiographs were done on the first postoperative day to assess the degree of
stone clearance and stent position. RESULTS: Age, gender, stone location and
stone size were not significantly different between both groups. In Group A, 31
(73.8%) children required ureteric dilation, 13 (31%) had a tight ureter that
failed to respond to dilation, 25 (59.5%) displayed complete stone clearance, and
of these, 13 (52%) needed postoperative stenting. One child experienced ureteric
injury during stone disintegration and was stented for two weeks. Children in
Group B experienced a 95.8% complete stone clearance rate, with no ureteric
injury reported; postoperative stenting was performed in three (12.5%) children..
CONCLUSION: Secondary ureteroscopy is preferable over primary ureteroscopy in
pediatric populations because of a significantly lower need for ureteric
dilation, shorter procedure time and better stone clearance rate..
PMID- 25138476
TI - Screening of mutations in NOL3 in a myoclonic syndromes series.
PMID- 25138477
TI - Clinical characteristics and outcome of intracerebral hemorrhage in young adults.
AB - Data on determinants of prognosis after intracerebral hemorrhage (ICH) in young
adults are scarce. Our aim was to identify clinical determinants of prognosis
after ICH in adults aged 18-50. We investigated 98 consecutive patients with an
ICH, aged 18-50 years, admitted to our hospital between 1980 and 2010. Collected
ICH characteristics included presenting symptoms, etiology, location, severity
and Glasgow Coma Scale (GCS). Outcomes were case-fatality (death within 30 days),
poor functional outcome (modified Rankin Scale >2), long-term mortality and
recurrent ICH. We assessed discriminatory power of factors associated with case
fatality [area under receiver operating curve (AUC)]. Case-fatality was 20.4 % (n
= 20) and well predicted by the GCS (AUC 0.83). Among 30-day survivors, a poor
functional outcome at discharge was present in 51.3 %. During a mean follow-up of
11.3 years mortality was only increased in patients aged 40-50 years
[standardized mortality ratio 4.8 (95 % CI 2.3-8.6)], but not in patients aged 18
40 years. Recurrent ICH occurred in 6 patients [10-year cumulative incidence 12.2
% (95 % CI 1.5-22.9 %)], all with the index ICH attributable to structural
vascular malformations. Prognosis after ICH in young adults is poor, mainly due
to high case-fatality, that is well predicted by the GCS. An exception is 30-day
survivors <40 years, who have a similar risk of dying as the general population.
Recurrence risk is especially present in patients with structural vascular
malformations, whereas risk seems to be very low in other patients.
PMID- 25138478
TI - Non-convulsive status epilepticus after ischemic stroke: a hospital-based stroke
cohort study.
AB - To evaluate in the setting of a stroke unit ward the usefulness of a prolonged
(>6 h) video-EEG recording (PVEEG) in identifying non-convulsive status
epilepticus (NCSE) in patients with an acute ischemic stroke. Predictors of NCSE
were also evaluated. Patients with an acute ischemic stroke, referred to our
unit, were included in this prospective observational study. A PVEEG recording
was implemented after stroke in all patients during the first week: (a) promptly
in those exhibiting a clear or suspected epileptic manifestation; (b) at any time
during the routine activity in the remaining patients. After the first week, a
standard EEG/PVEEG recording was hooked up only in presence of an evident or
suspected epileptic manifestation or as control of a previous epileptic episode.
NCSE was identified in 32 of the 889 patients (3.6 %) included in the study. It
occurred early (within the first week) in 20/32 (62.5 %) patients and late in the
remaining 12. Diagnosis was made on the basis of a specific clinical suspect (n =
19, 59.4 %) or without any suspect (n = 13, 40.6 %). In a multivariate analysis,
a significant association of NCSE was observed with NIHSS score, infarct size and
large atherothrombotic etiology. NCSE is not a rare event after an acute ischemic
stroke and a delayed diagnosis could worsen patient prognosis. Since NCSE can be
difficult to be diagnosed only on clinical grounds, implementation of a prompt
PVEEG should be kept available in a stroke unit whenever a patient develop signs,
although subtle, consistent with NCSE.
PMID- 25138479
TI - Fetal bronchoscopy as a useful procedure in a case with prenatal diagnosis of
congenital microcystic adenomatoid malformation.
AB - Massive microcystic congenital cystic adenomatoid malformation (CCAM) and
bronchial atresia are associated with a high perinatal mortality secondary to
lung hypoplasia and cardiac dysfunction, and fetal intervention should be
considered to improve prognosis. Therapeutic options include open fetal surgery
with pulmonary resection, fetal sclerotherapy and fetoscopy. We present a case
with a severely enlarged left lung without ultrasound signs of dilated airways
compatible with the diagnosis of microcystic CCAM, hydrops and severe
contralateral lung hypoplasia that was treated successfully at 30 weeks of
gestation by fetal bronchoscopy, through which bronchial atresia was identified
at the end of the left mainstem bronchi and permeabilized by laser ablation.
After fetal surgery, weekly follow-up showed a progressive decrease in the
affected lung size and an increase in the contralateral hypoplastic lung size,
demonstrating normal dimensions of both lungs at 34 weeks of gestation, reversal
of the mediastinal shift, and complete disappearance of hydrops. A healthy
neonate was delivered uneventfully at term with no need for respiratory support,
and the boy is now doing well at 15 months of age. This report demonstrates that
in cases with prenatal diagnosis of large microcystic CCAM, fetal bronchoscopy
can be used to refine the diagnosis of bronchial atresia and as a therapeutic
tool with good outcome.
PMID- 25138480
TI - Mobile teledermatology is a valid method to estimate prevalence of melanocytic
naevi in children.
AB - The prevalence of melanocytic naevi in children correlates with sun exposure and
may serve as an objective population risk indicator of future melanoma incidence.
The aim was to investigate if mobile teledermatology could offer a valid
methodology compared with standard manual, face-to-face counting of naevi on the
back of children. Ninety-seven children aged 7-16 years were enrolled. One
dermatologist performed manual naevi counting and imaging of the child's back
using an iPhone 4S comprising a safe-coded mobile application. Two other
dermatologists independently counted naevi from the images. Cohen's weighted
kappa (kappaw) coefficient demonstrated substantial agreement for both
dermatologists: kappaw = 0.69 (0.57-0.81 [95% confidence intervals]) and kappaw =
0.78 (0.70-0.86), compared with the manual assessment. Inter-rater reliability
was also substantial (kappaw = 0.80 [0.73-0.87]). Use of mobile teledermatology
proved valid for estimating naevi prevalence on the back and could provide a more
feasible methodology following trends in sun exposure in children.
PMID- 25138481
TI - ICEBERG: Intimal Carotid Evaluation Before Echocardiography Reveals Global
Vascular Risk.
AB - BACKGROUND: There is growing evidence that carotid ultrasonography provides
important prognostic information about cardiovascular risk assessment. Our
objective was to determine whether abbreviated rapid carotid ultrasonographic
screening would reveal important global vascular risk information in statin-naive
patients referred for routine transthoracic echocardiography (TTE). METHODS:
Abbreviated carotid ultrasonographic imaging was performed in 560 consecutive
patients undergoing TTE. The common carotid artery (CCA), the carotid bulb, and
the internal carotid artery (ICA) were scanned. Maximal CCA intima-media
thickness (IMT) was measured in the far wall. Carotid plaque was defined using
the Atherosclerosis Risk in Communities (ARIC) study criteria. RESULTS: Of the
2283 patients who underwent TTE during a 1-year period, a total of 560 patients
met inclusion criteria. There were 241 men, with a mean age of 63.2 +/- 12.8
years and a mean CCA IMT of 1.11 +/- 0.48 mm; 61% (147) had carotid plaque. The
319 women had a mean age of 66.3 +/- 10.8 years and a mean CCA IMT of 1.03 +/-
0.36 mm; 62.4% (199) had carotid plaque. All patients with plaque were considered
to be at high risk. CONCLUSIONS: Of the 560 consecutive statin-naive patients
referred for TTE with no history of vascular disease, a large proportion of both
men (61%) and women (62.4%) had carotid plaque, indicating a high risk for
vascular events according to the Canadian lipid guidelines. Although such
patients are seen in the echocardiography laboratory, the addition of an
abbreviated carotid ultrasonographic screening provides important information
regarding risk stratification and the implementation of preventive therapy.
PMID- 25138482
TI - Is plant-based cardioprotection evidence-based?
PMID- 25138483
TI - Stem cell therapy for the treatment of nonischemic cardiomyopathy: a systematic
review of the literature and meta-analysis of randomized controlled trials.
AB - BACKGROUND: Stem cell (SC) therapy improves left ventricular function and
dimensions in ischemic heart disease. Few small-scale trials have studied the
effects of SC therapy on nonischemic cardiomyopathy (CMP), the leading cause of
heart transplantation in the adults. The objectives were to gain a better insight
into the effects of SC therapy for nonischemic CMP by conducting a systematic
review of the literature and meta-analysis of randomized controlled trials.
METHODS: Medline, EBM Reviews-Cochrane Central Register of Controlled Trials,
Embase, and the ClinicalTrials.gov databases were screened for randomized
controlled trials involving SC for treatment of nonischemic CMP. Weighted mean
differences of improvement of left ventricular ejection fraction (LVEF) and left
ventricular end-diastolic diameter (LVEDD) were calculated using a random effect
analysis model. RESULTS: Four trials were included in this meta-analysis (244
patients). The weighted mean LVEF improvement was 4.87% (95% confidence interval,
1.32-8.43%) in the treatment group compared with the control group (P = 0.01).
The weighted mean decrease of LVEDD in the treatment group was of -2.19 mm (95%
confidence interval, -5.69 to 1.30) compared with the control group (P = 0.22).
On subgroup analysis, results were similar in studies involving peripheral CD34
positive or bone marrow-derived mononuclear cells (P = 0.33 for subgroup
differences). CONCLUSIONS: This is the first meta-analysis to show that for the
treatment of nonischemic CMP, SC therapy might improve LVEF, but not LVEDD.
Further trials should aim to circumscribe the optimal SC regimen in this setting,
and to assess long-term clinical outcomes as primary end points.
PMID- 25138484
TI - Purulent pericarditis after transbronchial biopsy.
AB - A 28-year-old woman experienced hypotension and unresponsiveness. She had
undergone bronchoscopy with needle biopsy 2 weeks before admission to evaluate
hilar lymphadenopathy given suspicion of sarcoidosis. She had an elevated white
blood cell count of 28,000/MUL and a serum creatinine level of 4.0 mg/dL.
Echocardiography showed a large pericardial effusion. Pericardiocentesis resulted
in removal of 400 mL of yellow-green purulent material that grew Streptococcus
milleri, Prevotella, Veillonella, and Peptostreptococcus species. Pericardiectomy
and mediastinal washout were performed. Subsequently, her condition rapidly
improved. She returned home after 26 days of admission. At 12-month follow-up,
the patient had made a full recovery.
PMID- 25138485
TI - Revascularization strategies for coronary disease: art or science?
PMID- 25138486
TI - Death and digoxin: stop me if you've heard this one before.
PMID- 25138487
TI - Improving efficiency of initial tests for efficacy in smoking cessation drug
discovery.
AB - INTRODUCTION: One obstacle to rapid development of new smoking cessation
medications is the inefficient early clinical evaluation of the efficacy of novel
drugs, which inform us as to whether or not to proceed with the greater expense
and time of more formal clinical trials. The vast majority of novel drugs fail to
show efficacy for cessation only after substantial resources have been spent and,
thus, are largely wasted. AREAS COVERED: The author reviews the general
limitations in the current typical procedures for initial tests of cessation
efficacy in novel drugs. Small, randomized clinical trials often have good
validity but may have practical limitations in achieving adequate statistical
power to test novel versus placebo treatment conditions. Lab tests of acute drug
effects on abstinence symptoms, during brief enforced cessation periods, are
practical but have limited clinical predictive validity. EXPERT OPINION: Initial
efficacy testing may be more efficient if done using innovative crossover designs
that evaluate brief 'practice' quit periods for both active and placebo
treatments within the same smokers, recruiting those high in quit motivation.
Because this approach would require far fewer subjects and a shorter duration of
testing, results could be obtained more rapidly and inexpensively to indicate
that a novel drug may, or may not, be sufficiently efficacious as to warrant the
greater costs and time of formal randomized clinical trials.
PMID- 25138488
TI - Clinical heterogeneity of the C9orf72 genetic mutation in frontotemporal
dementia.
AB - The C9orf72 genetic mutation represents the most common cause of familial
frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Studies
over the last 2 years have revealed a number of key features of this mutation in
the fields of clinical neurology, imaging, pathology, and genetics. Despite these
efforts, the clinical phenotype appears to extend beyond FTD and ALS into the
realm of psychiatric disease, and while highly variable survival rates have been
reported, the clinical course of carriers remains relatively unexplored. This
report describes two contrasting C9orf72 cases, one with a protracted indolent
course dominated by neuropsychiatric features and the other with a rapidly
progressive dementia. In both cases, initial structural brain imaging was
relatively normal.
PMID- 25138489
TI - A critical domain of Sweet potato chlorotic fleck virus nucleotide-binding
protein (NaBp) for RNA silencing suppression, nuclear localization and viral
pathogenesis.
AB - RNA silencing is an important mechanism of antiviral defence in plants. To
counteract this resistance mechanism, many viruses have evolved RNA silencing
suppressors. In this study, we analysed five proteins encoded by Sweet potato
chlorotic fleck virus (SPCFV) for their abilities to suppress RNA silencing using
a green fluorescent protein (GFP)-based transient expression assay in Nicotiana
benthamiana line 16c plants. Our results showed that a putative nucleotide
binding protein (NaBp), but not other proteins encoded by the virus, could
efficiently suppress local and systemic RNA silencing induced by either sense or
double-stranded RNA (dsRNA) molecules. Deletion mutation analysis of NaBp
demonstrated that the basic motif (an arginine-rich region) was critical for its
RNA silencing suppression activity. Using confocal laser scanning microscopy
imaging of transfected protoplasts expressing NaBp fused to GFP, we showed that
NaBp accumulated predominantly in the nucleus. Mutational analysis of NaBp
demonstrated that the basic motif represented part of the nuclear localization
signal. In addition, we demonstrated that the basic motif in NaBp was a
pathogenicity determinant in the Potato virus X (PVX) heterogeneous system.
Overall, our results demonstrate that the basic motif of SPCFV NaBp plays a
critical role in RNA silencing suppression, nuclear localization and viral
pathogenesis.
PMID- 25138490
TI - Structural classification and general principles for the design of spherical
molecular hosts.
AB - Cryptands, carcerands, polyoxometalates, and molecular capsules are cagelike
hosts that complex guests through encapsulation. Following the discovery of a
nanometer scale supramolecular shell-like spheroid, these and other shell-like
hosts were structurally classified. Their frameworks may be catalogued according
to principles of solid geometry. This has led to the identification of hosts that
have not yet been synthesized or discovered (such as the cuboctahedron shown;
X=O, S) and should lead to the design of additional container assemblies.
PMID- 25138491
TI - Crystalline bacterial cell surface layers (s layers): from supramolecular cell
structure to biomimetics and nanotechnology.
AB - An astonishingly broad application potential in biotechnology, biomimetics, and
nanotechnology is revealed by studies on the structure, chemistry, biosynthesis,
genetics, self-assembly, and function of supramolecular surface layers (S
layers). These are monomolecular, crystalline assemblies of protein or
glycoprotein subunits and represent one of the most commonly observed surface
structures of prokaryotic cell envelopes (see schematic representation of an
archaebacterial cell envelope).
PMID- 25138492
TI - Miniature continuous-flow polymerase chain reaction: a breakthrough?
AB - A time-space conversion enables the polymerase chain reaction (PCR) to be carried
out in a continuous-flow process: the mobile reaction mixture is pumped
continuously through a glass microchip and passes many times through three
constant temperature zones (see picture). The flow rate can be varied to obtain
an amplification time of only 90 s. When combined with other continuous-flow
microdevices this micromachine may prove useful for routine medical applications
and biochemical research.
PMID- 25138493
TI - Heterogenization of metallocene catalysts for alkene polymerization.
AB - Beyond mere convenience: In large-scale industrial processes for alkene
polymerization the essentially homogeneous metallocene/activator catalyst systems
are heterogenized (example shown) to improve polymer properties. New mesoporous
and organic catalyst supports and their application in this field of catalysis
are described.
PMID- 25138494
TI - Aromatic polyhedral hydroxyborates: bridging boron oxides and boron hydrides.
AB - No explosion, but per-B-hydroxylation occurs if the icosahedral boron hydrides
[closo-B12 H12 ](2-) (see picture), [closo-CB11 H12 ](-) , or closo-1,12-(CH2
OH)2 -1,12-C2 B10 H10 are refluxed in 30 % hydrogen peroxide. Thus, the three
isoelectronic species [closo-B12 (OH)12 ](2-) , [closo-1-H-1-CB11 (OH)11 ](-) ,
and closo-1,12-H2 -1,12-C2 B10 (OH)10 were obtained. ?=BH, ?=BOH.
PMID- 25138495
TI - The Equilibrium between Localized and Delocalized States of Thermochromic
Semibullvalenes and Barbaralanes-Direct Observation of Transition States of
Degenerate Cope Rearrangements.
AB - The UV/Vis spectra of thermochromic semibullvalenes 1 and barbaralanes recorded
at various temperatures yield enthalpy differences between the two degenerate
classical structures 1 and 1' and the less stable species (1*) that absorb at
long wavelengths. The latter species are interpreted in terms of higher,
delocalized states that are located just above the flat potential energy barrier
between the ground states (DeltaH(0) =11 (R=H; in butyronitrile), 1 kJ mol(-1)
(R=Ph)).
PMID- 25138496
TI - Solvent Effects on the Equilibrium between Localized and Delocalized States of
Thermochromic Semibullvalenes and Barbaralanes.
AB - The position of the equilibrium between localized and delocalized states of
thermochromic semibullvalenes and barbaralanes (see the Equation) depends
strongly on the solvent. Dipolar aprotic solvents, particularly N,N'
dimethylpropylene urea, favor the delocalized, bishomoaromatic state (DeltaH(0)
=8 kJ mol(-1) (cyclohexane), DeltaH(0) <0 kJ mol(-1) (N,N'-dimethylpropylene
urea)).
PMID- 25138497
TI - Efficient cleavage-cross-coupling strategy for solid-phase synthesis-a modular
building system for combinatorial chemistry.
AB - A new modular building system for the combinatorial chemistry was developed on
the basis of triazene linkers. Starting from an aniline system, further
functional units and virtually any alkene or alkyne as terminator furnished
lipophilic multicomponent systems in high yields and purities without the need
for purification steps (see schematic representation).
PMID- 25138498
TI - An oxidation-labile traceless linker for solid-phase synthesis.
AB - Traceless release of biaryls, acetylenes, alkenes, heterocycles, thioethers, and
secondary amines from different solid supports can be achieved under very mild
conditions by using a hydrazide group. This group, which is converted into an
acyl diazene by oxidation and subsequently cleaved by a nucleophile (see scheme),
is thus an attractive new linker for solid-phase synthesis and combinatorial
chemistry.
PMID- 25138499
TI - Design of new mesogenic block molecules: formation of columnar mesophases by
calamitic bolaamphiphiles with lateral lipophilic substituents.
AB - Rigid bolaamphiphiles with lateral alkyl chains such as 1 form columnar
mesophases of a novel type based on microsegregation of the three incompatible
parts of the molecules (shown schematically).
PMID- 25138500
TI - Catalytic asymmetric aminohydroxylation with amino-substituted heterocycles as
nitrogen sources.
AB - The suprafacial, vicinal addition of a heterocyclic moiety and a hydroxyl group
is achieved by the osmium-catalyzed asymmetric aminohydroxylation (AA) of olefins
with amino-substituted heterocycles as the nitrogen sources. Amino alcohols are
obtained in up to 97 % yield and with up to 99 % ee when a ligand derived from
dihydroquinidine (DHQD-L) is used [Eq. (1); R(i) indicates the remaining portion
of the heterocycle (Het); H2 O is the O source]. The AA can now be considered as
a means to directly introduce complex, biologically relevant substructures to
hydrocarbon backbones.
PMID- 25138501
TI - High-resolution calorimetry: new perspectives for the study of phase transitions.
AB - Only 7 pg of substance are needed to measure solid-solid phase transitions in n
alkanes with a new type of calorimeter (see schematic picture). This corresponds
to a transition heat of only 500 pJ. The small time constant of the calorimeter
additionally permits the observation of dynamic effects in the examined phase
transitions.
PMID- 25138503
TI - Solvothermal Synthesis of the Canted Antiferromagnet {K2 [CoO3 PCH2 N(CH2 CO2 )2
]}6 ?x H2 O.
AB - A rare example of a molecular species prepared by solvothermal synthesis is the
macrocyclic cobalt phosphonate/carboxylate 1, whose structure is shown
schematically. At low temperatures this compound displays spontaneous
magnetization due to canted antiferromagnetic ordering, which is very unusual for
a discrete molecular material.
PMID- 25138502
TI - Homoleptic lanthanide complexes of chelating phosphanamides-an experimental and
theoretical study.
AB - Four chelating ligands are present in the first phosphanamide complexes of Group
3 metals and the lanthanides (see structure shown). However, these ligands
coordinate to form a distorted molecular structure. The compounds were
characterized by single-crystal X-ray structure analysis and quantum-mechanical
investigations with density functional theory and MP2 methods.
PMID- 25138504
TI - C-C Bond Formation between Fischer Carbene Complexes and Allylic Alcohols by a
[3,4] Sigmatropic Rearrangement Promoted by a [1,2] M(CO)5 Shift.
AB - A [1,2] M(CO)5 shift promotes a [3,4] sigmatropic rearrangement after the
addition of allylic alcohols to Fischer alkenylcarbene complexes of tungsten or
chromium in the presence of alkoxide ions. This opens a new synthetic route to
the adducts 1. The reaction is also applicable to propargylic alcohols.
[M]=Mo(CO)5 , W(CO)5 .
PMID- 25138505
TI - Total synthesis of (+)-lactacystin.
AB - A double stereodifferentiating crotylation between aldehyde 1 and silane (S)-2 to
afford homoallylic alcohol 3 is the key diastereoselective step (anti:syn >30:1)
in an efficient asymmetric synthesis of (+)-lactacystin. This compound is a
metabolite isolated from Streptomyces sp. OM-6519 that exhibits significant
neurotrophic activity. An additional important step in the synthesis is a
catalytic asymmetric aminohydroxylation used as the key step in the synthesis of
the (2R,3S)-hydroxyleucine synthon.
PMID- 25138506
TI - Aerobic Oxidation of Primary Alcohols by a New Mononuclear Cu(II) -Radical
Catalyst.
AB - Primary alcohols such as ethanol or benzyl alcohol are selectively and
catalytically oxidized by the mononuclear copper(II) radical complex 1-a
functional model of the metalloenzyme galactose oxidase-with oxygen from air at
20 degrees C to give the corresponding aldehydes and H2 O2 in about 60 % yield.
PMID- 25138507
TI - Synthesis, Structure, and Redox Properties of [{(eta(5) -C5 H5 )Co(S2 C6 H4 )}2
Mo(CO)2 ], a Novel Metalladithiolene Cluster.
AB - Metal-metal bond formation by a cobaltadithiolene complex was observed for the
first time in the reaction of [Co(eta(5) -C5 H5 )(S2 C6 H4 )] with [Mo(CO)3 (py)3
] and BF3 to give the Co-Mo-Co cluster 1. Cyclic voltammetry reveals that 1
undergoes two one-electron reduction steps at the Co centers, which is indicative
of transmission of the Co-Co electronic interaction through the Mo center.
PMID- 25138508
TI - The Synthesis and Molecular Structure of the First Two-Coordinate, Dinuclear
sigma-Bonded Mercury(I) RHgHgR Compound.
AB - A linear Si-Hg-Hg-Si arrangement and a Hg-Hg distance of 265.69 pm are exhibited
by the first two-coordinate, dinuclear sigma-bonded organomercury(I) compound 1.
It was formed unexpectedly in the reaction of two equivalents of the silane (Me3
SiMe2 Si)3 SiH with tBu2 Hg. In contrast if the reagents are allowed to react in
a 1:1 ratio the expected mercury(II) compound (Me3 SiMe2 Si)3 SiHgtBu is
obtained.
PMID- 25138509
TI - Hexasupersilyl-triprismo-hexastannane (tBu3 Si)6 Sn6 -The First Molecular Tin
Compound Containing a Sn6 Prism.
AB - Dark violet hexastannane (tBu3 Si)6 Sn6 displays a new framework motif for
molecular tin compounds, in which six Sn atoms are located at the corners of a
trigonal prism. The compound can be synthesized according to Equation (a).
R*=SitBu3 .
PMID- 25138510
TI - Syntheses and ligating properties of molybdocene alkoxides-the first
heterodimetallic alkoxide containing molybdenum and bismuth.
AB - Fluorinated alkoxide ligands RO(-) (R=CH(CF3 )2 ) are the key to the isolation of
compounds of the type [Cp2 Mo(OR)2 ]. When electron-donating groups R are
employed, the Mo(OR)2 moiety can, and necessarily has to, serve as a ligand for
Lewis acidic fragments, allowing the isolation and structural characterization of
the first heterodimetallic alkoxide containing a Bi and a Mo center (1).
PMID- 25138511
TI - A spreader-bar approach to molecular architecture: formation of stable artificial
chemoreceptors.
AB - The destructive influence of lateral diffusion on nanostructured monolayers can
be prevented by using the spreader-bar technique. This approach allows the
formation of stable artificial receptors for barbituric acid by lateral
structuring of a dodecanethiol monolayer with molecular spreader-bars from
thiobarbituric acid without chemical polymerization (see schematic
representation). The new technique may have applications in chemosensors,
affinity chromatography, stereoselective catalysis, and molecular electronics.
PMID- 25138512
TI - Synthesis and Structures of cis- and trans-[Os(Bcat)(aryl)(CO)2 (PPh3 )2 ]:
Compounds of Relevance to the Metal-Catalyzed Hydroboration Reaction and the
Metal-Mediated Borylation of Arenes.
AB - Support for key steps of the mechanism for the transition metal catalyzed
hydroboration reaction is provided by the characterization and reactions of 1, a
cis-(boryl)(aryl) complex of osmium(II). This compound readily eliminates o
tolylBcat to give the osmium(0) intermediate 2, which in the presence of HBcat
reestablishes the osmium-boron bond by forming 3. R=o-tolyl, H2 cat=catechol=1,2
(HO)2 C6 H4 .
PMID- 25138513
TI - Thermally Stable Heterobinuclear Bivalent Group 14 Metal Complexes Ar2 M-Sn[1,8
(NR)2 C10 H6 ] (M=Ge, Sn; Ar=2,6-(Me2 N)2 C6 H3 ; R=CH2 tBu).
AB - The first thermally robust Ge(II) -Sn(II) compound 1 and the structurally
characterized Sn(II) -Sn(II) analogue 2, which maintain their structural
integrity in solution, were obtained by treating MAr2 (M=Ge, Sn; Ar=2,6-(Me2 N)2
C6 H3 ) with Sn[1,8-(NR2 )2 C10 H6 ] (R=CH2 tBu). On the basis of structural and
spectroscopic data, the M-Sn bond is regarded as the interaction of a MAr2 donor
with an Sn[1,8-(NR2 )2 C10 H6 ] acceptor.
PMID- 25138514
TI - Kinetic Resolution of Diiron Acyl Complexes-An Approach to Asymmetric Bicyclic
beta-Lactams.
AB - Kinetic resolution is achieved in the reaction of racemic diiron complexes like 1
with the chiral nitrone (-)-2. Oxidative removal of the metal and reductive
cleavage of the N-O bond provides beta-amino acids. This sequence was used in the
synthesis of beta-amino acids as well as the corresponding beta-lactams 4 (via
3).
PMID- 25138515
TI - Surface coordination chemistry: corrosion inhibition by tetranuclear cluster
formation of iron with salicylaldoxime.
AB - A tetranuclear iron cluster is the principal component of the purple coatings
produced by treating a mild steel surface with a salicylaldoxime corrosion
inhibitor. This was shown by comparison of the spectroscopic data with those of
the cluster [{Fe(salH)(HsalH)}4 ], which was obtained from FeCl3 and
salicylaldoxime (H2 salH) and has a distorted tetrahedral arrangement of Fe(III)
atoms coordinated by terminal (1-) and bridging (2-) salicylaldoximate ligands
(the central core of the cluster is depicted).
PMID- 25138516
TI - Stereoselective Solid-Phase Synthesis of beta-Lactams-A Novel
Cyclization/Cleavage Step towards 1-Oxacephams.
AB - Despite the antibiotic activity and the attractiveness of beta-lactams, the solid
phase synthesis of this class of compounds has been barely reported. Now the
diastereoselective synthesis of the 1-oxacepham 2 from the resin-bound beta
lactam derivative 1 has been achieved in five steps. The synthesis of 2 and other
1-oxacephams is attractive because all the reaction steps proceed in high yield,
the purity of the product is high, and the reaction sequence is simple.
PMID- 25138517
TI - A method for the selection of catalytic activity using phage display and
proximity coupling.
AB - Phage display has been used extensively for the selection of proteins with
binding sites for ligands. Here, as illustrated with the example of DNA
polymerase, the use of phage display for selection according to catalytic
activity is described. Active enzymes are selected by binding of the reaction
product P (see the scheme) cross-linked in the proximity of the enzyme E that
catalyzed the reaction with the substrate S.
PMID- 25138518
TI - Alkyl migration aptitudes in the vinylidene-acetylene rearrangement and isotope
effect in the vinylidene formation process from a deuterium-labeled cyclopropene.
AB - The secret of the mechanism of vinylidene rearrangements has been unlocked by the
use of specifically labeled cyclopropenes under mild thermal conditions (see the
Equations). (13) C labeling gives the surprising 1,2-alkyl migratory aptitude
sequence Et>iPr>Me. Deuterium labeling yields the first measurement of the
primary kinetic isotope effect in the ring opening of a cyclopropene to form a
vinylidene.
PMID- 25138519
TI - The First Total Synthesis of 6-Sulfo-de-N-acetylsialyl Lewis(x) Ganglioside: A
Superior Ligand for Human L-Selectin.
AB - Originally discovered as a minor by-product of 6-sulfo-N-acetylsialyl Lewis(x) ,
the de-N-acetylated form 1 is a superior L-selectin ligand to the N-acetyl form.
To substantiate the extraordinary reactivity of 1, it was synthesized for the
first time and its binding to L-selectin investigated. Compound 1 and related
structures may be high-affinity endogenous ligands for L-selectin that are
involved in the interaction of leukocytes with the vascular endothelium.
PMID- 25138520
TI - Metabolites with a novel c30 backbone from marine ciliates.
AB - Challenging questions are raised about the biosynthetic origin of vannusal A (1),
a metabolite that is isolated from the tropical marine ciliate Euplotes vannus
and contains an unusual C30 backbone.
PMID- 25138521
TI - Molecular Recognition within a Self-Assembled Cylindrical Host.
AB - A change in geometry is necessary on entry into the capsule: a supramolecular
associate approximately 1.8 nm long (see schematic representation), which
consists of two halves stabilized by hydrogen bonds, influences the intra- and
intermolecular interactions of the guest molecules encapsulated. Thus tertiary
amides and anilides such as 1, which exist in solution preferably as E rotamers,
are fixed in the Z conformation inside the capsule for steric reasons.
PMID- 25138522
TI - Is the Bis(MU-oxo)dicopper Core Capable of Hydroxylating an Arene?
AB - Direct attack of the bis(MU-oxo)dicopper core on an arene appears feasible in
tyrosinase and model complexes on the basis of studies of new [Cu(III) 2 (MU-O)2
](2+) compounds supported by bidentate imine/amine ligands. In the first
demonstration of such reactivity for a bis(MU-oxo)dicopper core, decomposition of
these intermediates caused hydroxylation of a pendant phenyl ring [Eq. (a)] in a
reaction analogous to that catalyzed by tyrosinase.
PMID- 25138523
TI - Cyclopropanation enantioselectivity is pressure dependent in supercritical
fluoroform.
AB - The tunable dielectric constant epsilon of supercritical fluoroform is the
explanation for pressure-dependent enantioselectivity in a reaction conducted at
low pressure. For the cyclopropanation of styrene and methyl phenyldiazoacetate
with a dirhodium catalyst, the enantioselectivity was significantly higher at 52
bar than above 80 bar (see plot).
PMID- 25138524
TI - A Diazoalkane Derivative of a Polyoxometalate: Preparation and Structure of [Mo6
O18 (NNC(C6 H4 OCH3 )CH3 )](2-).
AB - A new metathetical route to diazoalkane complexes is described which allows the
introduction of such ligands into previously inaccessible environments. The
method, which involves the exchange of oxo and [N2 CR2 ] ligands, is illustrated
by the preparation of the first diazoalkane-polyoxometalate complex 1.
PMID- 25138525
TI - Heterosupramolecular chemistry: programmed pseudorotaxane assembly at the surface
of a nanocrystal.
AB - Gold nanocrystals, stabilized by thiols covalently bound to a dibenzo[24]crown-8
moiety, have been programmed to recognize and selectively bind dibenzylammonium
cations in solution. This results in a self-organization process at the surface
of a nanocrystal with the assembly of a pseudorotaxane (see picture).
PMID- 25138526
TI - Structural abnormalities of corpus callosum and cortical axonal tracts
accompanied by decreased anxiety-like behavior and lowered sociability in spock3-
mutant mice.
AB - Spock3/Testican-3 is a nervous system-expressed heparan sulfate proteoglycan
belonging to a subgroup of the BM-40/SPARC/osteonectin family, the role of which
in brain development is unclear. Because Spock1, a member of the Spock family,
inhibits their attachment to substrates and the neurite outgrowth of cultured
neuronal cells, Spock3 is also thought to be similarly involved in the neuronal
development. In the present study, we established a Spock3-mutant mouse harboring
a deletion extending from the presumptive upstream regulatory region to exon 4 of
the Spock3 locus and performed histological and behavioral studies on these
mutant mice. In wild-type (WT) mice, all Spock members were clearly expressed
during brain development. In adults, intense Spock1 and Spock2 expressions were
observed throughout the entire brain; whereas, Spock3 expression was no longer
visible except in the thalamic nuclei. Thus, Spock3 expression is mostly confined
to the developmental stage of the brain. In adult mutant mice, the cells of all
cortical layers were swollen. The corpus callosum was narrowed around the central
region along the rostral-caudal axis and many small spaces were observed without
myelin sheaths throughout the entire corpus callosum. In addition, the cortical
input and output fibers did not form into thick bundled fibers as well as the WT
counterparts did. Moreover, a subpopulation of corticospinal axonal fibers
penetrated into the dorsal striatum with moderately altered orientations.
Consistent with these modifications of brain structures, the mutant mice
exhibited decreased anxiety-like behavior and lowered sociability. Together,
these results demonstrate that Spock3 plays an important role in the formation or
maintenance of major neuronal structures in the brain.
PMID- 25138527
TI - Global disulfide bond profiling for crude snake venom using dimethyl labeling
coupled with mass spectrometry and RADAR algorithm.
AB - Snake venom consists of toxin proteins with multiple disulfide linkages to
generate unique structures and biological functions. Determination of these
cysteine connections usually requires the purification of each protein followed
by structural analysis. In this study, dimethyl labeling coupled with LC-MS/MS
and RADAR algorithm was developed to identify the disulfide bonds in crude snake
venom. Without any protein separation, the disulfide linkages of several
cytotoxins and PLA2 could be solved, including more than 20 disulfide bonds. The
results show that this method is capable of analyzing protein mixture. In
addition, the approach was also used to compare native cytotoxin 3 (CTX III) and
its scrambled isomer, another category of protein mixture, for unknown disulfide
bonds. Two disulfide-linked peptides were observed in the native CTX III, and 10
in its scrambled form, X-CTX III. This is the first study that reports a platform
for the global cysteine connection analysis on a protein mixture. The proposed
method is simple and automatic, offering an efficient tool for structural and
functional studies of venom proteins.
PMID- 25138528
TI - Developmental trajectories of prejudice and tolerance toward immigrants from
early to late adolescence.
AB - Adolescence is an important period for the development of relationships between
immigrants and non-immigrants, yet little is known about how problematic
personality traits affect adolescents' relationships with and attitudes toward
immigrants. This work identified the roles of intergroup relationships and one
dimension of problematic personality traits, namely callous-unemotional traits,
in the development of adolescents' tolerance and prejudice. Three annual
measurements of a large community sample (N = 1,542) of non-immigrant adolescents
(M age = 15.31 at first measurement; 50.2% girls) were used to show that
tolerance and prejudice toward immigrants represent two dimensions with distinct
developmental trajectories from early to late adolescence. Callous-unemotional
traits predicted fewer decreases in prejudice toward immigrants, yet were not
directly associated with tolerance. Intergroup friendships predicted stronger
increases in tolerance, which, in turn, predicted decreases in prejudice toward
immigrants. Thus, tolerance and prejudice toward immigrants seem to be
differentially influenced by social experiences and problematic personality
traits.
PMID- 25138530
TI - Scenario planning for community development in Vietnam: a new tool for integrated
health approaches?
AB - BACKGROUND: Like many countries in Southeast Asia, Vietnam's rapid population and
economic growth has met challenges in infrastructure development, especially
sanitation in rural areas. OBJECTIVE: As an entry point, we developed scenario
planning as an action-research tool in a peri-urban community to identify first
steps towards improving their complex sanitation problem and to, systemically,
address emerging/re-emerging infectious diseases, as these are commonly linked to
unsafe water and inadequate sanitation conditions. As an integrated approach, the
process of constructing scenarios allowed us to work across sectors and
stakeholders to incorporate this knowledge into a common vision. DESIGN: We
conducted focus group discussions to identify and rank driving forces, orally
constructed scenarios for the most uncertain drivers, discussed scenario
implications and options, and examined the overall process for usefulness and
sustainability. During a one-month scoping phase and in between focus group
meetings, we carried out household visits which helped us understand the context
of data and gather feedback from participants outside of the formal data
collection process. Recorded results from these activities were used to develop
subsequent tools. RESULTS AND CONCLUSIONS: The research process gave us insights
into how to adapt the scenario planning tool to identify alternative options.
This involved choosing boundary partners, negotiating priorities, drawing out
participant learning through self-assessment of our process (a prerequisite for
changing mental models and thus achieving outcomes), and understanding how
conveyed messages may reinforce the status quo. These insights showed the
importance of examining research results beyond outputs and outcomes, namely
through process.
PMID- 25138529
TI - Effects of advanced glycation end products on calcium handling in cardiomyocytes.
AB - BACKGROUND AND AIMS: Advanced glycation end products (AGEs) accumulate in
diabetes and the engagement of receptor for AGE (RAGE) by AGEs contributes to the
pathogenesis of diabetic cardiomyopathy. This study aims to investigate the
effects of AGE/RAGE on ryanodine receptor (RyR) activity and Ca(2+) handling in
cardiomyocytes to elucidate the possible mechanism underlying cardiac dysfunction
in diabetic cardiomypathy. METHODS AND RESULTS: Confocal imaging Ca(2+) spark,
the elementary Ca(2+) release event reflecting RyR activity in intact cell, as
well as SR Ca(2+) content and systolic Ca(2+) transient were performed in
cultured neonatal rat ventricular myocytes. The results show that 50 mg/ml AGE
increased the frequency of Ca(2+) sparks by 160%, while 150 mg/ml AGE increased
it by 53%. AGE decreased the amplitude, width and duration of Ca(2+) sparks.
Blocking RAGE with anti-RAGE IgG completely abolished the alteration of Ca(2+)
sparks. The SR Ca(2+) content indicated by the amplitude (DeltaF/F0) of 20 mM
caffeine-elicited Ca(2+) transient was significantly decreased by 150 mg/ml AGE.
In parallel, the amplitude of systolic Ca(2+) transient evoked by 1 Hz-field
stimulation was remarkably decreased by 150 mg/ml AGE. The anti-RAGE antibody
completely restored the impaired SR load and systolic Ca(2+) transient.
CONCLUSION: AGE/RAGE signal enhanced Ca(2+) spark-mediated SR Ca(2+) leak,
causing partial depletion of SR Ca(2+) content and consequently decreasing
systolic Ca(2+) transient, which may contribute to contractile dysfunction in
diabetic cardiomyopathy.
PMID- 25138531
TI - Experiences in anti-tuberculosis treatment in patients with multiple previous
treatments and its impact on drug resistant tuberculosis epidemics.
AB - BACKGROUND: Tuberculosis (TB) patients with a history of multiple anti-TB
treatments are the 'neglected' group to the free anti-TB treatment policy in
China. OBJECTIVE: To understand the experiences of TB patients with multiple
previous treatments with regard to bacteriological diagnosis and treatment
regimens, especially for second-line anti-TB drugs, and how this might influence
the risks of multidrug and extensively drug-resistant TB (M/XDR-TB). DESIGN: A
cross-sectional study was conducted in 10 county/district TB clinics in five
provinces of China. The study participants were TB patients that had at least two
previous treatment episodes that lasted longer than 1 month each. Face-to-face
interviews and drug susceptibility testing (DST) were conducted with the
consenting participants. RESULTS: A total of 328 TB patients were recruited. The
proportion of multidrug-resistant tuberculosis (MDR-TB) was 58.2% in the 287 DST
confirmed patients. Forty-two percent of the patients did not complete their
first treatment course. About 23.8% of the participants had a history of taking
second-line drugs, and more than 77.8% of them were treated in county TB
dispensaries where only sputum microscopy was applied. Multivariate analysis
found that the use of second-line drugs was significantly associated with
frequency of previous treatments (p<0.01), but not with drug resistance profiles
of patients. CONCLUSIONS: Patients with multiple previous treatments are at
extremely high risk of MDR-TB in China. The unregulated use of second-line drugs
bring about the threat of XDR-TB epidemic. DST-guided treatment and strict
regulations of anti-TB treatment should be assured for the high-risk TB patients
for the prevention and control of M/XDR-TB.
PMID- 25138532
TI - Interpretive focus groups: a participatory method for interpreting and extending
secondary analysis of qualitative data.
AB - BACKGROUND: Participatory approaches to qualitative research practice constantly
change in response to evolving research environments. Researchers are
increasingly encouraged to undertake secondary analysis of qualitative data,
despite epistemological and ethical challenges. Interpretive focus groups can be
described as a more participative method for groups to analyse qualitative data.
OBJECTIVE: To facilitate interpretive focus groups with women in Papua New Guinea
to extend analysis of existing qualitative data and co-create new primary data.
The purpose of this was to inform a transformational grounded theory and
subsequent health promoting action. DESIGN: A two-step approach was used in a
grounded theory study about how women experience male circumcision in Papua New
Guinea. Participants analysed portions or 'chunks' of existing qualitative data
in story circles and built upon this analysis by using the visual research method
of storyboarding. RESULTS: New understandings of the data were evoked when women
in interpretive focus groups analysed the data 'chunks'. Interpretive focus
groups encouraged women to share their personal experiences about male
circumcision. The visual method of storyboarding enabled women to draw pictures
to represent their experiences. This provided an additional focus for whole-of
group discussions about the research topic. CONCLUSIONS: Interpretive focus
groups offer opportunity to enhance trustworthiness of findings when researchers
undertake secondary analysis of qualitative data. The co-analysis of existing
data and co-generation of new data between research participants and researchers
informed an emergent transformational grounded theory and subsequent health
promoting action.
PMID- 25138533
TI - Paracelsus in nanotoxicology.
PMID- 25138535
TI - Ubiquitin-activating enzyme is necessary for 17beta-estradiol-induced breast
cancer cell proliferation and migration.
AB - The sex steroid hormone 17beta-estradiol (E2) regulates breast cancer (BC) cell
proliferation and migration through the activation of a plethora of signal
transduction cascades (e.g., PI3K/AKT activation) starting after E2 binding to
the estrogen receptor alpha (ERalpha). The activity of the ubiquitin (Ub)-system
modulates many physiological processes (e.g., cell proliferation and migration),
and recently, a specific inhibitor (Pyr-41) of the Ub-activating enzyme (E1),
which works as the activator of the Ub-based signaling, has been identified to
prevent the functions of the Ub-system. Here, by using Pyr-41, we studied the
involvement of the Ub-system in E2-induced signaling to proliferation and
migration of BC cells. Our data indicate that E1 activity is involved in the
E2:ERalpha signaling important for cell proliferation and migration through the
modulation of the E2-evoked activation of the PI3K/AKT and the p38/MAPK pathways.
These discoveries indicate a new molecular circuitry that can be further explored
to define new opportunities for BC treatment.
PMID- 25138537
TI - Changes in sexual signals are greater than changes in ecological traits in a
dichromatic group of fishes.
AB - Understanding the mechanisms by which phenotypic divergence occurs is central to
speciation research. These mechanisms can be revealed by measuring differences in
traits that are subject to different selection pressures; greater influence of
different types of selection can be inferred from greater divergence in
associated traits. Here, we address the potential roles of natural and sexual
selection in promoting phenotypic divergence between species of snubnose darters
by comparing differences in body shape, an ecologically relevant trait, and male
color, a sexual signal. Body shape was measured using geometric morphometrics,
and male color was measured using digital photography and visual system-dependent
color values. Differences in male color are larger than differences in body shape
across eight allopatric, phylogenetically independent species pairs. While this
does not exclude the action of divergent natural selection, our results suggest a
relatively more important role for sexual selection in promoting recent
divergence in darters. Variation in the relative differences between male color
and body shape across species pairs reflects the continuous nature of speciation
mechanisms, ranging from ecological speciation to speciation by sexual selection
alone.
PMID- 25138536
TI - The provision of mental health treatment after screening: exploring the
relationship between treatment setting and treatment intensity.
AB - OBJECTIVE: Primary care screening programs for mental health disorders are
designed to detect patients who might benefit from treatment. As such, the
utility of these programs is predicated on the actions that take place in
response to a positive screen. Our objective was to characterize the cascade of
care delivery steps following a positive screen for a mental health disorder.
METHOD: We examined the care received by primary care patients over the year
following a new positive screen for depression, posttraumatic stress disorder
(PTSD) or alcohol misuse. We characterized whether the care adhered to practice
guidelines for related mental health disorders and whether involvement of mental
health specialists led to higher use of guideline-adherent practices. RESULTS:
Many patients received appropriate treatment in the primary care setting and
those whose scores were consistent with more severe illness were more likely to
receive care in a mental health setting. Patients with positive screens for
depression and PTSD who went on to be seen in mental health clinics received care
that was consistent with treatment guidelines for the related disorder most of
the time. In the case of patients with positive screens for alcohol misuse, few
received guideline-recommended medications in any setting. However, a substantial
portion of patients received some alcohol-related counseling from their primary
care physicians during the visit in which their alcohol misuse was detected.
CONCLUSION: It appears that the treatment system for mental health problems,
which extends from primary care settings to mental health subspecialty settings,
can provide adequate care when patients' mental health problems are identified
through screening. The care provided in all settings can be improved, and
additional steps to enhance the quality of care are warranted. This should
include additional efforts to align screening and treatment.
PMID- 25138538
TI - Single-stage multiple-tract percutaneous nephrolithotomy in the treatment of
staghorn stones under total ultrasonography guidance.
AB - OBJECTIVE: To evaluate the safety and efficacy of single-stage multiple-tract
percutaneous nephrolithotomy (PCNL) in the treatment of staghorn stones solely
guided by ultrasonography (US). PATIENTS AND METHODS: From May 2007 to July 2012,
55 single-stage multiple-tract PCNL procedures were performed (53 patients, of
whom 2 had bilateral stones). Caliceal puncture and dilatation were performed
under US guidance in all cases. The procedure was evaluated for access success,
length of postoperative hospital stay, complications (modified Clavien system),
and stone clearance. RESULTS: The mean (+/-SD) operating time was 84.87 +/- 24.9
min, with a mean (+/-SD) postoperative hospital stay of 5.2 +/- 1.31 days. The
patients experienced a mean (+/-SD) decrease in hemoglobin level of 8.23 +/- 2.39
g/l and the stone-free rate after single-stage surgery was 78.18%. Extracorporeal
shock wave lithotripsy was indicated in 2 cases as an auxiliary treatment. There
were 10 grade 1 (62.5%) and 6 grade 2 (37.5%) complications; however, there were
no complications above grade 3. CONCLUSION: Total US-guided single-stage multiple
tract PCNL for treating staghorn calculi in selected cases is safe, feasible, and
may be performed with an acceptable morbidity and with the advantage of
preventing radiation hazards and damage to adjacent organs.
PMID- 25138539
TI - Dextrin/poly (HEMA): pH responsive porous hydrogel for controlled release of
ciprofloxacin.
AB - Herein, we report an oral route administration for ciprofloxacin hydrochloride
delivery using dextrin and poly (2-hydroxyethyl methylacrylate) based crosslinked
hydrogel (c-Dxt/pHEMA). Various characteristics such as FTIR spectra, XRD
analyses, UV-VIS-NIR spectra, FESEM and E-SEM analyses, rheological
characteristics, gel kinetics, deswelling characteristics as well as
biodegradation study of the hydrogel have been carried out. FTIR, XRD along with
solid state UV-VIS-NIR analyses explain the good compatibility between the drug
and the hydrogel matrix. The in vitro release study demonstrates that c-Dxt/pHEMA
releases ciprofloxacin in a sustained way (33.75% of drug has been released in
18h) and is expected to be a promising matrix for ciprofloxacin carrier. The
release kinetics and mechanism suggest that drug release follows first order
kinetics and non-Fickian diffusion mechanism. Finally, the hydrogel shows
excellent physical stability as carrier for ciprofloxacin up to 3 months.
PMID- 25138534
TI - Loss of PiT-1 results in abnormal endocytosis in the yolk sac visceral endoderm.
AB - PiT-1 protein is a transmembrane sodium-dependent phosphate (Pi) transporter. PiT
1 knock out (KO) embryos die from largely unknown causes by embryonic day (E)
12.5. We tested the hypothesis that PiT-1 is required for endocytosis in the
embryonic yolk sac (YS) visceral endoderm (VE). Here we present data supporting
that PiT-1 KO results in a YS remodeling defect and decreased endocytosis in the
YS VE. The remodeling defect is not due to an upstream cardiomyocyte requirement
for PiT-1, as SM22alphaCre-specific KO of PiT-1 in the developing heart and the
YS mesodermal layer (ME) does not recapitulate the PiT-1 global KO phenotype.
Furthermore, we find that high levels of PiT-1 protein localize to the YS VE
apical membrane. Together these data support that PiT-1 is likely required in YS
VE. During normal development maternal immunoglobulin (IgG) is endocytosed into
YS VE and accumulates in the apical side of the VE in a specialized lysosome
termed the apical vacuole (AV). We have identified a reduction in PiT-1 KO VE
cell height and a striking loss of IgG accumulation in the PiT-1 KO VE. The
endocytosis genes Tfeb, Lamtor2 and Snx2 are increased at the RNA level.
Lysotracker Red staining reveals a loss of distinct AVs, and yolk sacs incubated
ex vivo with phRODO Green Dextran for Endocytosis demonstrate a functional loss
of endocytosis. As yolk sac endocytosis is controlled in part by microautophagy,
but expression of LC3 had not been examined, we investigated LC3 expression
during yolk sac development and found stage-specific LC3 RNA expression that is
predominantly from the YS VE layer at E9.5. Normalized LC3-II protein levels are
decreased in the PiT-1 KO YS, supporting a requirement for PiT-1 in autophagy in
the YS. Therefore, we propose the novel idea that PiT-1 is central to the
regulation of endocytosis and autophagy in the YS VE.
PMID- 25138540
TI - Adsorption of copper(II) ions by a chitosan-oxalate complex biosorbent.
AB - Oxalic acid, an effective metal-chelating ligand, is abundant in natural
resources. In this study, a chitosan-oxalate complex biosorbent (COCB) was
prepared by an iontropic cross-linking method. The COCB beads were characterized
by Fourier transform infrared (FT-IR) spectra, X-ray diffraction (XRD) and
thermogravimetric analysis (TGA). The XRD analysis shows that Cu(II) ions can
form complexes with chitosan and oxalate. Adsorption of Cu(II) ions onto COCB
beads was pH-dependent. The isothermal adsorption data fitted well to Langmuir
equation with the maximum adsorption capacities of 227.27 mg/g for porous COCB
beads and 175.44 mg/g for non-porous COCB beads at pH 5.0. The adsorption
kinetics described by the pseudo-second-order diffusion models, suggesting that
the rate-limiting step in adsorption was chemical sorption. Thermodynamic
parameters (DeltaG degrees <0 and DeltaH degrees >0) indicated a spontaneous and
endothermic adsorption process. The COCB bioadsorbent exhibited fast adsorption
rate and high adsorption capacity for Cu(II) uptake.
PMID- 25138541
TI - Solvent effects on polymer sorting of carbon nanotubes with applications in
printed electronics.
AB - Regioregular poly(3-alkylthiophene) (P3AT) polymers have been previously reported
for the selective, high-yield dispersion of semiconducting single-walled carbon
nanotubes (SWCNTs) in toluene. Here, five alternative solvents are investigated,
namely, tetrahydrofuran, decalin, tetralin, m-xylene, and o-xylene, for the
dispersion of SWCNTs by poly(3-dodecylthiophene) P3DDT. The dispersion yield
could be increased to over 40% using decalin or o-xylene as the solvents while
maintaining high selectivity towards semiconducting SWCNTs. Molecular dynamics
(MD) simulations in explicit solvents are used to explain the improved sorting
yield. In addition, a general mechanism is proposed to explain the selective
dispersion of semiconducting SWCNTs by conjugated polymers. The possibility to
perform selective sorting of semiconducting SWCNTs using various solvents
provides a greater diversity of semiconducting SWCNT ink properties, such as
boiling point, viscosity, and surface tension as well as toxicity. The efficacy
of these new semiconducting SWCNT inks is demonstrated by using the high boiling
point and high viscosity solvent tetralin for inkjet-printed transistors, where
solvent properties are more compatible with the inkjet printing head and improved
droplet formation.
PMID- 25138542
TI - Bone augmentation using a synthetic hydroxyapatite/silica oxide-based and a
xenogenic hydroxyapatite-based bone substitute materials with and without
recombinant human bone morphogenetic protein-2.
AB - AIM: To test whether or not bone regeneration using deproteinized bovine bone
mineral (DBBM) is comparable to hydroxyapatite/silica oxide (HA/SiO) and to test
the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) as an
adjunct to DBBM for localized bone regeneration. MATERIALS AND METHODS: In each
of the 10 rabbits, 4 titanium cylinders were placed on the external cortical
plates of their calvaria. Four treatment modalities were randomly allocated: (i)
empty, (ii) HA/SiO, (iii) DBBM, and (iv) DBBM plus rhBMP-2 (DBBM/BMP). The
animals were sacrificed at week 8. Descriptive histology and histomorphometric
assessment using a superimposed test grid of points and cycloids were performed.
RESULTS: The mean number of points of the test grid coinciding with bone within
the cylinder reached 124 +/- 35 bone points for empty controls, 92 +/- 40 bone
points for DBBM, 98 +/- 44 bone points for synthetic HA/SiO, and 146 +/- 34 bone
points DBBM/BMP. The P-value for DBBM with and without BMP reached a borderline
statistical significance of 0.051. However, the area of bone regeneration within
the cylinders peaked for DBBM/BMP and was statistically significantly higher
compared with empty cylinders (P < 0.05). The bone-to-bone substitute contact
ranged between 32.9% +/- 21.7 for DBBM, 39.6 +/- 18.4% for HA/SiO, and 57.8% +/-
10.2 for DBBM/BMP. The differences between DBBM/BMP and controls (DBBM, HA/SiO)
were statistically significant (P < 0.05). CONCLUSIONS: DBBM and HA/SiO rendered
comparable amounts of bone regeneration. The addition of rhBMP-2 to DBBM resulted
in more favorable outcomes with respect to the area of bone regeneration and to
bone-to-implant contact, thereby indicating the potential of this growth factor
to enhance bone regeneration within this animal model.
PMID- 25138543
TI - Successful peripheral neuromodulation for phantom limb pain.
AB - SETTING: For decades, the heterogeneity of the amputee population and the complex
interaction of biopsychosocial factors have confounded researchers' attempts to
develop an effective treatment for phantom limb pain. Therefore, it remains
difficult to treat, and affected patients often experience decreased quality of
life, increased psychological distress, and poorer health outcomes. PATIENT: In
the case study, we report a novel strategy for the peripheral placement of
neuromodulation leads for the treatment of phantom limb pain in a patient who
subsequently described complete and consistent pain relief independent of
significant variations in psychosocial stress.
PMID- 25138544
TI - Injury Response of Resected Human Brain Tissue In Vitro.
AB - Brain injury affects a significant number of people each year. Organotypic
cultures from resected normal neocortical tissue provide unique opportunities to
study the cellular and neuropathological consequences of severe injury of adult
human brain tissue in vitro. The in vitro injuries caused by resection
(interruption of the circulation) and aggravated by the preparation of slices
(severed neuronal and glial processes and blood vessels) reflect the reaction of
human brain tissue to severe injury. We investigated this process using
immunocytochemical markers, reverse transcriptase quantitative polymerase chain
reaction and Western blot analysis. Essential features were rapid shrinkage of
neurons, loss of neuronal marker expression and proliferation of reactive cells
that expressed Nestin and Vimentin. Also, microglia generally responded strongly,
whereas the response of glial fibrillary acidic protein-positive astrocytes
appeared to be more variable. Importantly, some reactive cells also expressed
both microglia and astrocytic markers, thus confounding their origin. Comparison
with post-mortem human brain tissue obtained at rapid autopsies suggested that
the reactive process is not a consequence of epilepsy.
PMID- 25138545
TI - Characterization of adipose-derived stem cells of anatomical region from mice.
AB - BACKGROUND: Stem cells constitute a group of great capacity for self-renewal,
long-term viability, and multi-lineage potential. Several studies have provided
evidence that adipose tissue represents an alternative source of stem cells, with
the main benefit of adipose-derived stem cells being that they can be easily
harvested from patients by a simple minimally invasive method and can be easily
cultured. The aim of this study was to establish a culture protocol for obtaining
and characterizing adipose-derived stem cells (ADSCs) from C57BL/6 J mice.
RESULTS: The results showed that the yield, viability, and cell morphology
obtained differ according to the age of isolated anatomic regions of the adipose
tissue from ovarian and epididymis. The results of determination of cyclin D1
showed uniformity in the expression between different populations of ADSCs. A
significant increase in the expression of caspase-3 active, was also observed in
large cell populations from mice after 120 days. ADSCs were positive for
mesenchymal markers CD90 and CD105, Nanog, SSEA-1, CD106, and VEGFR-1, and
negative for hematopoietic markers CD34 and CD45. A large number of cells in S +
G2/M phases was also observed for both sexes, demonstrating high proliferative
capacity of ADSCs. CONCLUSIONS: We observed that the adipose tissue of C57BL/6 J
mice, isolated from the studied anatomic regions, is a promising source for
obtaining pluripotent mesenchymal stem cells with high viability and
proliferative response.
PMID- 25138546
TI - Neuromarkers of fatigue and cognitive complaints following chemotherapy for
breast cancer: a prospective fMRI investigation.
AB - The aim of this study is to use functional magnetic resonance imaging (fMRI) to
prospectively examine pre-treatment predictors of post-treatment fatigue and
cognitive dysfunction in women treated with adjuvant chemotherapy for breast
cancer. Fatigue and cognitive dysfunction often co-occur in women treated for
breast cancer. We hypothesized that pre-treatment factors, unrelated to
chemotherapy per se, might increase vulnerability to post-treatment fatigue and
cognitive dysfunction. Patients treated with (n = 28) or without chemotherapy (n
= 37) and healthy controls (n = 32) were scanned coincident with pre- and one
month post-chemotherapy during a verbal working memory task (VWMT) and assessed
for fatigue, worry, and cognitive dysfunction. fMRI activity measures in the
frontoparietal executive network were used in multiple linear regression to
predict post-treatment fatigue and cognitive function. The chemotherapy group
reported greater pre-treatment fatigue than controls and showed compromised
neural response, characterized by higher spatial variance in executive network
activity, than the non-chemotherapy group. Also, the chemotherapy group reported
greater post-treatment fatigue than the other groups. Linear regression indicated
that pre-treatment spatial variance in executive network activation predicted
post-treatment fatigue severity and cognitive complaints, while treatment group,
age, hemoglobin, worry, and mean executive network activity levels did not
predict these outcomes. Pre-treatment neural inefficiency (indexed by high
spatial variance) in the executive network, which supports attention and working
memory, was a better predictor of post-treatment cognitive and fatigue complaints
than exposure to chemotherapy per se. This executive network compromise could be
a pre-treatment neuromarker of risk, indicating patients most likely to benefit
from early intervention for fatigue and cognitive dysfunction.
PMID- 25138547
TI - Effects of radioiodine treatment for differentiated thyroid cancer on testis
function.
AB - OBJECTIVE: To evaluate the effects of radioactive iodine (RAI) treatment for
differentiated thyroid cancer (DTC) on testis function. DESIGN: A prospective
longitudinal single-centre study was performed. A comprehensive andrological
evaluation including hormonal assessment, semen analysis and scrotal ultrasound
was undertaken in male patients undergoing RAI treatment for DTC. METHODS:
Hormonal assessment of FSH, LH, testosterone (T), sperm concentration and
motility and testis volume were determined in 20 patients in basal conditions, 6
and 12 months after RAI. Results were analysed in the whole group of patients and
then separately in those who received one single ablative treatment ('Single'
group, n = 10) and those who received multiple treatments ('Multiple' group, n =
10). RESULTS: In basal conditions, 3 of 20 (15%) patients had a reduced sperm
count and belonged to the 'Multiple' group. After RAI, an increase of FSH (8.8 +/
1.2 UI/l vs 5.2 +/- 1.2, P < 0.005) and a decrease in sperm concentration (28.8
+/- 7.7 millions/ml vs 54.5 +/- 7.1, P < 0.005) and testis volume (15.2 +/- 3.1
vs 13.7 +/- 0.8 ml, P < 0.005) occurred at 6 months in the whole group. One year
after RAI, seven patients had oligozoospermia (five from the 'Multiple' group and
two from the 'Single' group). Permanent impairment of one or more testis function
parameters was observed in patients who underwent multiple RAI treatments: 50%
for sperm count, 40% for FSH levels and testis volume and, respectively, in 20
and 10% of those who received one single RAI treatment. CONCLUSIONS: The single
ablative RAI treatment in cancer patients is better tolerated respect multiple
RAI treatments regard testis function. Multiple treatments for recurrent or
metastatic disease may cause a permanent impairment of one or more parameters
related to the reproductive potential of male patients.
PMID- 25138548
TI - Irreversible airway obstruction assessed by high-resolution computed tomography
(HRCT), exhaled nitric oxide (FENO), and biological markers in induced sputum in
patients with asthma.
AB - OBJECTIVE: The objective of this study was to explore the significance of
assessing irreversible airway obstruction (IAO) in asthma patients by high
resolution computed tomography (HRCT), biological markers in induced sputum, and
exhaled nitric oxide (FENO). METHODS: The study was conducted in 34 patients with
IAO, 46 patients with reversible airway obstruction (RAO), 40 patients who did
not have airway obstruction (NAO), and 40 healthy subjects serving as controls.
These patients received a step therapy for at least 3 months based on the
guidelines for the prevention and treatment of asthma. After achieving complete
or partial control of asthma, HRCT, lung function, FENO, and chemokine levels in
induced sputum were measured. RESULTS: The airway wall area (WA; %) correlated
with forced expiratory volume-1 (FEV-1(L); r = -0.67, p < 0.0001), and
significant differences in bronchial wall thickening (BWT) of the LEVEL E
generation airways were observed between the asthma and control groups (p <
0.01). FENO levels correlated with FEV-1 (%) in the IAO group (r = 0.49, p =
0.01). The levels of matrix metalloproteases-9 (MMP-9) and tissue inhibitor of
matrix metalloproteinase-1 (TIMP-1) in asthma patients with IAO, RAO, and NAO
were significantly higher than those in the controls (p < 0.05). The level of
neutrophilia in the sputum from the IAO group was higher than that from the RAO,
NAO and control groups. CONCLUSION: Asthma patients with IAO have an increased
BWT. Airway measurements with HRCT scans appear to be valuable in the evaluation
of airway remodeling in asthma patients with IAO.
PMID- 25138549
TI - Dabigatran: patient management in specific clinical settings.
AB - Dabigatran, a direct thrombin inhibitor, is licensed for the prevention of venous
thromboembolism after knee and hip replacement, the prevention of stroke and
systemic embolism in patients with non-valvular atrial fibrillation and for the
treatment of acute venous thromboembolism. As dabigatran has a favourable benefit
risk profile, it is being increasingly used. Dabigatran differs from vitamin K
antagonists as regards its pharmacological characteristics and its impact on
certain laboratory tests, and also in the lack of a direct antagonist that can
reverse dabigatran-induced anticoagulation. In emergency settings such as acute
bleeding, emergency surgery, acute coronary syndrome, thrombolysis for ischaemic
stroke or overdosing, specific strategies are required. A working group of
experts from various disciplines has developed strategies for the management of
dabigatran-treated patients in emergency settings.
PMID- 25138551
TI - Skeletal (stromal) stem cells: an update on intracellular signaling pathways
controlling osteoblast differentiation.
AB - Skeletal (marrow stromal) stem cells (BMSCs) are a group of multipotent cells
that reside in the bone marrow stroma and can differentiate into osteoblasts,
chondrocytes and adipocytes. Studying signaling pathways that regulate BMSC
differentiation into osteoblastic cells is a strategy for identifying druggable
targets for enhancing bone formation. This review will discuss the functions and
the molecular mechanisms of action on osteoblast differentiation and bone
formation; of a number of recently identified regulatory molecules: the non
canonical Notch signaling molecule Delta-like 1/preadipocyte factor 1 (Dlk1/Pref
1), the Wnt co-receptor Lrp5 and intracellular kinases. This article is part of a
Special Issue entitled: Stem Cells and Bone.
PMID- 25138550
TI - MicroRNA-17/20a inhibits glucocorticoid-induced osteoclast differentiation and
function through targeting RANKL expression in osteoblast cells.
AB - Glucocorticoids act on the osteoblasts to up-regulate the expression of RANKL,
which is very important in the etiology of glucocorticoid-induced osteoclast
differentiation and bone resorption. The mechanisms of this process are still not
completely understood. Recent studies have shown that glucocorticoids mediate
osteoblast function by decreasing the expression of microRNA-17-92a cluster.
Coincidentally, we found that the microRNA-17/20a (microRNA-17, microRNA-20a)
seed sequences were also complementary to a sequence conserved in the 3'-
untranslated region of RANKL mRNA. Therefore, we hypothesized that
glucocorticoids might promote osteoblast-derived RANKL expression by down
regulating microRNA-17/20a, which favors differentiation and function of the
osteoclasts. In the present study, Western blot analysis showed that microRNA
17/20a markedly lowered the levels of RANKL protein and attenuated dexamethasone
induced RANKL expression in the osteoblasts. The post-transcriptional repression
of RANKL by microRNA-17/20a was further confirmed by the luciferase reporter
assay. Furthermore, we found that dexamethasone-induced osteoclast
differentiation and function were significantly attenuated in co-culture with
osteoblast over-expressed microRNA-17/20a and osteoclast progenitors. These
results showed that microRNA-17/20a may play a significant role in glucocorticoid
induced osteoclast differentiation and function by targeting the RANKL expression
in osteoblast cells.
PMID- 25138552
TI - Mathematical modelling and optimization of synthetic textile dye removal using
soil composites as highly competent liner material.
AB - Soil is widely used as adsorbent for removing toxic pollutants from their aqueous
solutions due to its wide availability and cost efficiency. This study
investigates the potential of soil and soil composites for removal of crystal
violet (CV) dye from solution on a comparative scale. Optimisation of different
process parameters was carried out using a novel approach of response surface
methodology (RSM) and a central composite design (CCD) was used for determining
the optimum experimental conditions, as well as the result of their interactions.
Around 99.85 % removal of CV was obtained at initial pH 6.4, which further
increased to 99.98 % on using soil and cement composite proving it to be the best
admixture of those selected. The phenomenon was found to be represented best by
the Langmuir isotherm at different temperatures. The process followed the pseudo
second-order kinetic model and was determined to be spontaneous chemisorption in
nature. This adsorbent can hence be suggested as an appropriate liner material
for the removal of CV dye.
PMID- 25138553
TI - Spatial distribution of heavy metal contamination in soils near a primitive e
waste recycling site.
AB - The total concentrations of 12 heavy metals in surface soils (SS, 0-20 cm),
middle soils (MS, 30-50 cm) and deep soils (DS, 60-80 cm) from an acid-leaching
area, a deserted paddy field and a deserted area of Guiyu were measured. The
results showed that the acid-leaching area was heavily contaminated with heavy
metals, especially in SS. The mean concentrations of Ni, Cu, Zn, Cd, Sn, Sb and
Pb in SS from the acid-leaching area were 278.4, 684.1, 572.8, 1.36, 3,472, 1,706
and 222.8 mg/kg, respectively. Heavy metal pollution in the deserted paddy field
was mainly concentrated in SS and MS. The average values of Sb in SS and MS from
the deserted paddy field were 16.3 and 20.2 mg/kg, respectively. However, heavy
metal contamination of the deserted area was principally found in the DS.
Extremely high concentrations of heavy metals were also observed at some special
research sites, further confirming that the level of heavy metal pollution was
very serious. The geoaccumulation index (Igeo) values revealed that the acid
leaching area was severely polluted with heavy metals in the order of Sb > Sn >
Cu > Cd > Ni > Zn > Pb, while deserted paddy field was contaminated predominately
by metals in the order of Sb > Sn > Cu. It was obvious that the concentrations of
some uncommon contaminants, such as Sb and Sn, were higher than principal
contaminants, such as Ni, Cu, Zn and Pb, suggesting that particular attention
should be directed to Sn and Sb contamination in the future research of heavy
metals in soils from e-waste-processing areas. Correlation analysis suggested
that Li and Be in soils from the acid-leaching area and its surrounding
environment might have originated from other industrial activities and from
batteries, whereas Ni, Cu, Zn, Cd, Pb, Sn and Sb contamination was most likely
caused by uncontrolled electronic waste (e-waste) processing. These results
indicate the significant need for optimisation of e-waste-dismantling
technologies and remediation of polluted soil environment.
PMID- 25138554
TI - Hydroxyl radical reaction rate coefficients as a function of temperature and IR
absorption cross sections for CF3CH=CH2 (HFO-1243zf), potential replacement of
CF3CH2F (HFC-134a).
AB - CF3CH=CH2 (hydrofluoroolefin, HFO-1243zf) is a potential replacement of high
global-warming potential (GWP) hydrofluorocarbon (HFC-134a, CF3CFH2). Both the
atmospheric lifetime and the radiative efficiency of HFO-1243zf are parameters
needed for estimating the GWP of this species. Therefore, the aim of this work is
(i) to estimate the atmospheric lifetime of HFO-1243zf from the reported OH rate
coefficients, k OH, determined under tropospheric conditions and (ii) to
calculate its radiative efficiency from the reported IR absorption cross
sections. The OH rate coefficient at 298 K also allows the estimation of the
photochemical ozone creation potential (epsilon(POCP)). The pulsed laser
photolysis coupled to a laser-induced fluorescence technique was used to
determine k OH for the reaction of OH radicals with HFO-1243zf as a function of
pressure (50-650 Torr of He) and temperature (263-358 K). Gas-phase IR spectra of
HFO-1243zf were recorded at room temperature using a Fourier transform IR
spectrometer between 500 and 4,000 cm(-1). At all temperatures, k OH did not
depend on bath gas concentration (i.e., on the total pressure between 50 and 650
Torr of He). A slight but noticeable T dependence of k OH was observed in the
temperature range investigated. The observed behavior is well described by the
following Arrhenius expression: k OH(T) = (7.65 +/- 0.26) * 10(-13) exp [(165 +/-
10) / T] cm(3) molecule(-1) s(-1). Negligible IR absorption of HFO-1243zf was
observed at wavenumbers greater than 1,700 cm(-1). Therefore, IR absorption cross
sections, [Formula: see text], were determined in the 500-1,700 cm(-1) range.
Integrated [Formula: see text] were determined between 650 and 1,800 cm(-1) for
comparison purposes. The main diurnal removal pathway for HFO-1243zf is the
reaction with OH radicals, which accounts for 64% of the overall loss by
homogeneous reactions at 298 K. Globally, the lifetime due to OH reaction (tau
OH) was estimated to be 8.7 days under the assumption of a well-mixed atmosphere.
Assuming other removal pathways, the atmospheric lifetime (tau) was estimated to
be ~6 days. Considering the estimated tau OH and the measured IR absorption cross
sections of HFO-1243zf in the atmospheric window (720-1,250 cm(-1)), its lifetime
corrected radiative efficiency was calculated to be 0.019 W m(-2) ppbv(-1).
GWP100 years for the HFO investigated, 0.29, is negligible compared to that of
HFC-134a, the HFC to be potentially replaced (GWP100 years = 1,300, Hodnebrog et
al. (Rev Geophys 51:300-378, 2013)). epsilon POCP for HFO-1243zf was estimated to
be around 1 order of magnitude lower than that for ethylene. In conclusion, HFO
1243zf is fast degraded in the atmosphere, and it does not appreciably contribute
to global warming and local/regional air pollution. Therefore, HFO-1243zf can be
a suitable replacement for HFC-134a in air conditioning units.
PMID- 25138555
TI - Evaluating the genotoxicity of urban PM2.5 using PCR-based methods in human lung
cells and the Salmonella TA98 reverse test.
AB - A number of compounds found in particulate matter with an aerodynamic diameter
<2.5 (PM2.5) can interact with DNA either directly or after enzymatic
transformation to induce DNA modifications. These particulate matter (PM)-induced
alterations in DNA may be associated with increased frequencies of pollution
associated diseases, such as lung cancer. In the present study, we applied
different methods to assess the mutagenicity and genotoxicity of monthly PM2.5
organic extracts collected over a full year. We used the Salmonella assay,
exposed cultured human embryonic lung fibroblasts and applied extracellular
lactate dehydrogenase (LDH) and 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H
tetrazolium-5-carboxyanilide inner salt (XTT) assays to assess the cytotoxicity
of PM2.5 on the cells. We assessed both the expression levels of a number of DNA
repair genes (using qRT-qPCR) and the genetic profile of the treated cells
compared to the control. The expression levels of XRCC1 and APE1, which are
involved in the first steps of base excision repair, as well as ERCC1, XPA and
XPF, which encode nucleotide excision repair subunits, were analysed. The monthly
mean of the PM2.5 collected was 35.16 +/- 22.06 MUg/m(3). The mutagenicity of
PM2.5 to TA98 was 46 +/- 50 net revertants/m(3), while the mutagenicity to TA98 +
S9 was 17 +/- 19 net revertants/m(3). The mean IC50 values were 2.741 +/- 1.414
and 3.219 +/- 2.764 m(3) of equivalent air in the XTT and LDH assays,
respectively. A marked and significant increase in APE1 expression levels was
observed in the exposed cells. This effect was also significantly correlated with
mutagenicity (p < 0.01). No induced AFLP fragment profile alterations were
detected. The proposed approach seems to be useful for integrated evaluation and
for highlighting the mechanisms inducing DNA damage.
PMID- 25138557
TI - Chemical extractability of As and Pb from soils across long-term abandoned
metallic mine sites in Korea and their phytoavailability assessed by Brassica
juncea.
AB - The chemical extractability of As and Pb (by 5 mM CaCl2, 0.1 M HCl, 0.05 M NH4
(H2PO4), and aqua regia) from soils and their phytoavailability (by Brassica
juncea) were assessed using 16 soil samples collected as a function of distance
from mine pits across three long-term abandoned metallic mine sites. The total
concentrations of As and Pb (17-41,000 and 27-10,047 mg kg(-1), respectively)
decreased with increasing separation distance from the mine pits along a
declining slope. However, the percentage of chemically leachable As and Pb mass
(e.g., by 5 mM CaCl2, 0.1 M HCl, or 0.05 M NH4(H2PO4)) relative to total mass
(e.g., by aqua regia) tended to increase exponentially with distance, indicating
more chemically labile fractions present in less contaminated downgradient soils.
Among soil components, extractable As concentrations were best described by
coupling DCB-Al with other Al and Fe oxides. For Pb concentration, pH coupled to
DCB-Al or Ox-Al provided a good predictive relationship. The inhibitory growth
and uptake by plants were best correlated with the extractable concentrations by
5 mM CaCl2 and 0.1 M HCl. In conclusion, the chemical extractability and
phytoavailability of As and Pb are highly influenced by the relative labile
fraction in abandoned mine soils, and its distribution in soils is essentially
correlated with sampling distance from mine pits.
PMID- 25138556
TI - Endocrine actions of pesticides measured in the Flemish environment and health
studies (FLEHS I and II).
AB - Within the Flemish Environment and Health studies (FLEHS I, 2002-2006, and FLEHS
II, 2007-2012), pesticide exposure, hormone levels and degree of sexual
maturation were measured in 14-15-year-old adolescents residing in Flanders
(Belgium). In FLEHS II, geometric mean concentrations (with 95 % confidence
interval (CI)) of 307 (277-341) and 36.5 ng L(-1) (34.0-39.2) were found for p,p'
dichlorophenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB). These
values were respectively 26 and 60 % lower than levels in FLEHS I, 5 years
earlier. Metabolites of organophosphorus pesticides (OPPs) and of para
dichlorobenzene were measured for the first time in FLEHS II, yielding
concentrations of 11.4, 3.27 and 1.57 MUg L(-1) for the sum of dimethyl- and
diethyl phosphate metabolites and 2,5-dichlorophenol (2,5-DCP), respectively.
Data on internal exposure of HCB showed a positive correlation with sexual
maturation, testosterone and the aromatase index for boys and with free thyroxine
(fT4) and thyroid stimulating hormone (TSH) (both boys and girls). For both p,p'
DDE and HCB, a negative association with sexual development in girls was found.
The OPP metabolites were negatively associated with sex hormone levels in the
blood of boys and with sexual maturation (both boys and girls). The pesticide
metabolite 2,5-DCP was negatively correlated with free T4, while a positive
association with TSH was reported (boys and girls). These results show that even
exposure to relatively low concentrations of pesticides can have significant
influences on hormone levels and the degree of sexual maturation in 14-15-year
old adolescents.
PMID- 25138558
TI - Leaf-age and soil-plant relationships: key factors for reporting trace-elements
hyperaccumulation by plants and design applications.
AB - Relationships between the trace-elements (TE) content of plants and associated
soil have been widely investigated especially to understand the ecology of TE
hyperaccumulating species to develop applications using TE phytoextraction. Many
studies have focused on the possibility of quantifying the soil TE fraction
available to plants, and used bioconcentration (BC) as a measure of the plants
ability to absorb TE. However, BC only offers a static view of the dynamic
phenomenon of TE accumulation. Accumulation kinetics are required to fully
account for TE distributions in plants. They are also crucial to design
applications where maximum TE concentrations in plant leaves are needed. This
paper provides a review of studies of BC (i.e. soil-plant relationships) and leaf
age in relation to TE hyperaccumulation. The paper focuses of Ni and Mn
accumulators and hyperaccumulators from New Caledonia who were previously
overlooked until recent Ecocatalysis applications emerged for such species.
Updated data on Mn hyperaccumulators and accumulators from New Caledonia are also
presented and advocate further investigation of the hyperaccumulation of this
element. Results show that leaf-age should be considered in the design of sample
collection and allowed the reclassification of Grevillea meisneri known
previously as a Mn accumulator to a Mn hyperaccumulator.
PMID- 25138559
TI - Environmental chemicals mediated the effect of old housing on adult health
problems: US NHANES, 2009-2010.
AB - Housing conditions affect occupants continuously, and health interventions have
shown a positive association between housing investment or improvement and
occupant's health. However, the sources of the housing problems were less
understood. Since it was observed that lead dust and chloroanisoles released from
housing (materials) as indoor pollutants affected child's health, we now aimed to
examine the relationships among built year, environmental chemicals and
individual health in adults in a national and population-based setting. Data were
retrieved from the US National Health and Nutrition Examination Survey, 2009
2010, including demographics, housing characteristics, self-reported health
status, biomarkers and blood and urinary chemical concentrations. Adults aged 20
and above were included for statistical analysis (n = 5,793). Analysis involved
chi-square test, t test, and survey-weighted general linear regression and
logistic regression modelling. People who resided in older housing built before
1990 tended to report chronic bronchitis, liver problems, stroke, heart failure,
diabetes, asthma and emphysema. Higher values in HDL cholesterol, blood lead and
blood cadmium and having positive responses of hepatitis A, B, C and E antibodies
among occupants were also observed. Furthermore, higher environmental chemical
concentrations related to old housing including urinary cadmium, cobalt,
platinum, mercury, 2,5-dichlorophenol and 2,4-dichlorophenol concentrations and
mono-cyclohexyl phthalate and mono-isobutyl phthalate metabolites were shown in
occupants as well. Older housing (>=30 years) seemed to contribute to the amount
of environmental chemicals that affected human health. Regular monitoring,
upgrading and renovation of housing to remove environmental chemicals and policy
to support people in deprived situations against environmental injustice would be
needed.
PMID- 25138560
TI - Cancer risks and long-term community-level exposure to pentachlorophenol in
contaminated areas, China.
AB - Widespread use of pentachlorophenol (PCP) in schistosomiasis endemic areas had
led to ubiquitous exposure to PCP and its residues. Numerous studies had revealed
that occupational PCP exposure probably increased risk of cancers, but whether
long-term community-level exposure to PCP generates the similarly carcinogenic
effect, seldom studies focused on it. This study was to explore the cancer risks
of long-term community-level PCP exposure from drinking water in a Chinese
general population. Incident (2009-2012) cancer records were identified by local
government national registry. And PCP concentration of raw drinking water samples
in each district was measured by GC-MS/MS analysis for further division of three
PCP exposure categories by interquartile range (high vs. medium vs. low).
Internal comparisons were performed, and standard rate ratio was calculated to
describe the relationship between PCP exposure and cancer risks by using low
exposure group as the reference group. PCP was detected in all 27 raw drinking
water samples ranging from 11.21 to 684.00 ng/L. A total of 6,750 cases (4,409
male and 2,341 female cases) were identified, and age-standardized rate (world)
was 154.95 per 100,000 person-years. The cancer incidence for the high-exposure
group was remarkably high. Internal comparisons indicated that high PCP exposure
might be positively associated with high cancer risks in the community
population, particularly for leukemia (SRR = 5.93, 95 % CI = 5.24-6.71), maligant
lymphoma (SRR = 2.27, 95 % CI = 2.10-2.54), and esophageal cancer (SRR = 2.42, 95
% CI = 2.35-2.50). Long-term community-level exposure to PCP was probably
associated with hemolymph neoplasm, neurologic tumors, and digestive system
neoplasm.
PMID- 25138561
TI - Differential effect of water-soluble chitin on collagen synthesis of human bone
marrow stem cells and human periodontal ligament stem cells.
AB - Human bone marrow stem cells (hBMSCs) represent a promising regenerative material
because of their mutipotency, including their ability to regenerate collagenous
soft tissues. We previously found that water-soluble chitin (WSC) enhances the
ability of human periodontal ligament stem cells (hPDLSCs) to synthesize collagen
tissue. The aim of this study was to determine the effects of WSC on hBMSCs and
hPDLSCs for the collagen synthesis both in vitro and in vivo. hBMSCs and hPDLSCs
were isolated and expanded with or without 0.3 mg/mL WSC. A series of in vitro
and in vivo analyses were performed to evaluate their characteristics as stem
cell populations. Then, collagen and hydroxyproline assays were conducted using
both in vitro and in vivo assay models, and the real-time polymerase chain
reaction was performed to analyze the expression of collagen-related markers. WSC
treated and nontreated hBMSCs and hPDLSCs were transplanted into
immunocompromised mice, and histology and immunohistochemistry analyses were
conducted after 8 weeks. The in vitro results showed that those cells possessed
the characteristics of mesenchymal stem cells. The amount of soluble collagen
synthesized was significantly greater in WSC-treated hBMSCs than in the
nontreated group; conversely, treatment of hPDLSCs with WSC decreased the
formation of soluble collagen. The amount of insoluble collagen synthesized was
greater in the WSC-treated groups than in the nontreated groups for both hBMSCs
and hPDLSCs. The hydroxyproline contents of the regenerated soluble and insoluble
collagens were similar. The expressions of mRNA for collagen types I-V,
hyaluronic acid synthase 1 (HAS1), HAS2, and HAS3, and the LOX family were higher
in WSC-treated hPDLSCs than in the nontreated group, whereas WSC increased the
expression of collagen type III and decreased that of collagen type I in hBMSCs.
The histology and immunohistochemistry results revealed that WSC significantly
increased the amount of collagen formed in vivo by both types of stem cells.
Collectively, treatment with WSC significantly enhanced the collagen-forming
potentials of hBMSCs and hPDLSCs, but the collagen they produced exhibited
distinctively different characteristics. These findings suggest that the
appropriate stem-cell source should be chosen based on the purpose of the
required regenerated tissue.
PMID- 25138562
TI - The expression of glucocorticoid receptor is negatively regulated by active
androgen receptor signaling in prostate tumors.
AB - The glucocorticoid and androgen receptors (GR and AR) can commonly regulate up to
50% of their target genes in prostate cancer (PCa) cells. GR expression is
stimulated by castration therapy, which has been proposed to be one mechanism
that compensates for AR signaling blockade and promotes castration-resistant PCa
(CRPC) progression. However, whether GR functions as a driver for CRPC or a
marker reflecting AR activity remains unclear. Here, we applied PCa tissue
microarrays to show that GR protein levels were elevated by castration therapy,
but reduced to pre-castration levels when tumors were at the CRPC stage. Using
subrenal capsule xenograft models, we showed that GR expression was inversely
correlated with AR and PSA expressions. GR expression levels are not associated
with tumor invasion and metastasis phenotypes. In castration-resistant C4-2
xenografts expressing AR shRNA, regressing tumors induced by AR knockdown
expressed higher levels of GR and lower levels of PSA than non-regressing tumors.
Immunoblotting and real-time PCR assays further showed that AR knockdown or AR
antagonists increased GR expression at both mRNA and protein levels. ChIP
combined with DNA sequencing techniques identified a negative androgen responsive
element (nARE) 160K base pairs upstream of the GR gene. Gel shift assays
confirmed that AR directly interacted with the nARE and luciferase assays
demonstrated that the nARE could mediate transcription repression by ligand
activated AR. In conclusion, GR expression is negatively regulated by AR
signaling and may serve as a marker for AR signaling in prostate tumors.
PMID- 25138563
TI - Beta-blocking agents in cardiovascular disease; are they here to stay?
PMID- 25138564
TI - Allergen analysis of sea urchin roe using sera from five patients.
AB - BACKGROUND: Sea urchin roe can cause anaphylactic reactions the first time they
are consumed; therefore, careful clinical attention should be paid to their
effects. However, no previous study has examined the allergens in sea urchin roe
using sera from more than one patient. We attempted to identify sea urchin
allergens using sera from 5 patients with sea urchin allergies. METHODS: We
enrolled 5 patients with relevant medical histories, positive results on a skin
prick test and/or a food challenge test, and high levels of sea urchin-specific
IgE in an enzyme-linked immunosorbent assay. We performed SDS-PAGE,
immunoblotting, immunoblot inhibition, and N-terminal amino acid sequence
detection. RESULTS: Ten protein bands ranging from 18 to 170 kDa were detected in
more than 2 patients' sera. In immunoblotting, the protein band for the 170-kDa
major yolk protein was recognized by 4 of the 5 sera. Furthermore, the reaction
between IgE and the protein band for egg cortical vesicle protein (18 kDa) was
inhibited by the addition of salmon roe extract. CONCLUSION: Major yolk protein
was confirmed to be one of the main allergens in sea urchin roe. In addition, egg
cortical vesicle protein (18 kDa) was demonstrated to be an important protein for
cross-reactivity with salmon roe.
PMID- 25138566
TI - 'They said it was bronchiolitis; is it going to turn into asthma doctor?'.
AB - Acute bronchiolitis is a common paediatric disease of infancy. Its association
with subsequent asthma development has puzzled clinicians and epidemiologists for
decades. This article reviews the current state of knowledge regarding the role
of acute bronchiolitis in the inception of asthma. There is little doubt that
acute bronchiolitis is associated with an increased risk of recurrent wheezing
throughout the primary school years although the direction of causality--i.e.
whether bronchiolitis in infancy leads to asthma or it merely represents the
first clinical presentation of predisposition to asthma--is uncertain. Existing
evidence suggests that both host factors (e.g. prematurity, atopic
predisposition) and acute viral infection characteristics (e.g. type of virus,
severity) are operating in this relationship, perhaps with variable involvement
in different individuals. Further clarification of these issues will help
paediatricians provide evidence-based information regarding the long-term
prognosis of this common disease to the families, and at the same time, it will
facilitate prophylactic approaches and therapeutic strategies.
PMID- 25138567
TI - Teaching nursing concepts through an online discussion board.
AB - Barriers to course content engagement and student learning in nursing education
abound. Some of these barriers include content overload, classroom time
constraints, and large student numbers. One way to overcome these issues is the
implementation of active learning strategies in the classroom. Despite the
positive learning outcomes associated with active learning strategies described
in the education literature, traditional passive learning strategies continue to
be used by nurse educators in the classroom. This article details the results of
a pilot study using an active teaching strategy-an online discussion board-which
was designed to improve the learning engagement of beginning nursing students
enrolled in their first face-to-face nursing course. The results of the semester
long pilot study indicated a favorable student response to the active teaching
strategy and improved overall success in the course by the students who
participated fully in the online discussions.
PMID- 25138568
TI - Integrating Reiki and community-engaged scholarship: an interdisciplinary
educational innovation.
AB - To provide students with a meaningful holistic care experience while integrating
community-engaged scholarship, students partnered with a Reiki-prepared faculty
member within a nurse-managed community clinic to offer Reiki to the clients and
participate in the evaluation of the effectiveness of the modality. This article
describes how students and faculty integrated holistic care, scholarship, and
community engagement. This experience provided the students with an opportunity
to embrace the art and science of holistic nursing while obtaining experience in
measuring outcomes.
PMID- 25138565
TI - Childhood maltreatment and the risk of pre-pregnancy obesity and excessive
gestational weight gain.
AB - The objective of this study was to estimate whether maternal history of childhood
maltreatment was associated with pre-pregnancy obesity or excessive gestational
weight gain. Pregnant women (n = 472) reported pre-pregnancy weight and height
and gestational weight gain and were followed up to 16 years post-partum when
they reported maltreatment on the Childhood Trauma Questionnaire (CTQ). CTQ score
ranged from no maltreatment (25) to severe maltreatment (125). Prenatal mental
health modified the association between CTQ score and maternal weight (P < 0.15),
and thus stratified models are presented. After adjusting for race, prenatal
tobacco, marijuana and alcohol use, a one standard deviation (1 SD) increase in
CTQ score was associated with a 45% increase in the risk of pre-pregnancy obesity
among the 141 women with elevated anxiety (>=75th percentile on the State Trait
Anxiety Inventory) [relative risk, RR (95% confidence interval, CI): 1.45 (1.12,
1.88)], but was not associated among less anxious (<75th percentile) women [RR
(95% CI): 1.10 (0.81, 1.51)]. Risk of excessive gestational weight gain was
higher [adjusted RR (95% CI): 1.21 (1.07, 1.37)] with every 1 SD increase in CTQ
score for anxious women. No association was observed for less anxious women
[adjusted RR (95% CI): 0.89 (0.78, 1.02)]. Prenatal depression similarly modified
the association between maltreatment and weight gain. Factors such as
psychological status and traumatic experiences in early childhood may contribute
to pre-pregnancy obesity and excessive gestational weight gain.
PMID- 25138569
TI - Three-calendar-year Bachelor of Science in Nursing: an innovative curriculum
program.
AB - The 3-calendar-year Bachelor of Science in Nursing (BSN) curriculum program was
developed to facilitate a quicker entry into professional nursing practice. This
program offered many advantages, including financial and time-saving benefits for
students, more efficient use of campus facilities, and flexibility in faculty
scheduling. Evaluation of the program showed benefits in the success rate of
course-work, in retention and graduation rates, and in subsequent NCLEX-RN pass
rates. The NCLEX-RN pass rate for students in the 3-calendar-year BSN program was
98.33%, compared with the national average pass rate (88.01%) for the same 5-year
period for first-time test takers. The 3-calendar-year BSN program met the needs
of both traditional and nontraditional students. It produced quality nurse
graduates who were successful NCLEX-RN first-time test takers. The program has
potential to be adopted by other universities with a student base composed of
individuals of modest resources and diverse backgrounds.
PMID- 25138570
TI - Meaningful learning: theoretical support for concept-based teaching.
AB - Novice nurses' inability to transfer classroom knowledge to the bedside has been
implicated in adverse patient outcomes, including death. Concept-based teaching
is a pedagogy found to improve knowledge transfer. Concept-based teaching
emanates from a constructivist paradigm of teaching and learning and can be
implemented most effectively when the underlying theory and principles are
applied. Ausubel's theory of meaningful learning and its construct of substantive
knowledge integration provides a model to help educators to understand,
implement, and evaluate concept-based teaching. Contemporary findings from the
fields of cognitive psychology, human development, and neurobiology provide
empirical evidence of the relationship between concept-based teaching, meaningful
learning, and knowledge transfer. This article describes constructivist
principles and meaningful learning as they apply to nursing pedagogy.
PMID- 25138571
TI - Habitat differences influence genetic impacts of human land use on the American
beech (Fagus grandifolia).
AB - Natural reforestation after regional forest clearance is a globally common land
use sequence. The genetic recovery of tree populations in these recolonized
forests may depend on the biogeographic setting of the landscape, for instance
whether they are in the core or in the marginal part of the species' range. Using
data from 501 individuals genotyped across 7 microsatellites, we investigated
whether regional differences in habitat quality affected the recovery of genetic
variation in a wind-pollinated tree species, American beech (Fagus grandifolia)
in Massachusetts. We compared populations in forests that were recolonized
following agricultural abandonment to those in remnant forests that have only
been logged in both central inland and marginal coastal regions. Across all
populations in our entire study region, recolonized forests showed limited
reduction of genetic diversity as only observed heterozygosity was significantly
reduced in these forests (H(O) = 0.520 and 0.590, respectively). Within inland
region, this pattern was observed, whereas in the coast, recolonized populations
exhibited no reduction in all genetic diversity estimates. However, genetic
differentiation among recolonized populations in marginal coastal habitat
increased (F(st) logged = 0.072; F(st) secondary = 0.249), with populations
showing strong genetic structure, in contrast to inland region. These results
indicate that the magnitude of recovery of genetic variation in recolonized
populations can vary at different habitats.
PMID- 25138572
TI - Improving immunogenicity and efficacy of vaccines for genital herpes containing
herpes simplex virus glycoprotein D.
AB - No vaccines are approved for prevention or treatment of genital herpes. The focus
of genital herpes vaccine trials has been on prevention using herpes simplex
virus type 2 (HSV-2) glycoprotein D (gD2) alone or combined with glycoprotein B.
These prevention trials did not achieve their primary end points. However, subset
analyses reported some positive outcomes in each study. The most recent trial was
the Herpevac Trial for Women that used gD2 with monophosphoryl lipid A and alum
as adjuvants in herpes simplex virus type 1 (HSV-1) and HSV-2 seronegative women.
Unexpectedly, the vaccine prevented genital disease by HSV-1 but not HSV-2.
Currently, HSV-1 causes more first episodes of genital herpes than HSV-2,
highlighting the importance of protecting against HSV-1. The scientific community
is conflicted between abandoning vaccine efforts that include gD2 and building
upon the partial successes of previous trials. We favor building upon success and
present approaches to improve outcomes of gD2-based subunit antigen vaccines.
PMID- 25138573
TI - The influence of antioxidant THPC on the properties of polymer gel dosimeter.
AB - In order to decrease the negative influence of oxygen to the response of PAG
dosimeters THPC has been added to the gel in the role of scavenger. Apart from
the decreased influence of oxygen, THPC also influences other properties of gel
dosimeters. This study examines these influences and their quantification.
Previous studies have shown that increasing the concentration of THPC causes a
decreasing response of the dosimeter (as measured in the relaxation rate R2).
Evaluation of the IR spectrum of gels irradiated by a variety of doses has shown
that it is caused mostly by the changed structure of the arising polymer, not due
to the decreased polymerization. THPC also changes the kinetics of the subsequent
reactions in the gel after the end of irradiation. THPC has its influence also on
the size of the dose response overshoot that happens in the areas of steep dose
gradients. An easy model of action in the gel was suggested, which allows one to
estimate the size and kinetics of the changed response of the dosimeter after the
end of irradiation depending on the content of THPC, the size of the dose and the
dose gradient.
PMID- 25138574
TI - Comparative effects of metformin and pioglitazone on YKL-40 in type 2 diabetes: a
randomized clinical trial.
AB - PURPOSE: Metformin and pioglitazone are believed to exert their long-term
benefits by means of amelioration of chronic low-grade inflammation, a key event
in development of diabetes and its long-term complications. The present trial was
designed to investigate the comparative efficacy of the two anti-diabetes
medications on serum concentrations of YKL-40, a novel marker of inflammation.
METHODS: In a parallel-group, open-label, randomized trial setting
(ClinicalTrials.gov Identifier No. NCT01521624), 84 newly diagnosed, medication
naive type 2 diabetes patients were assigned to metformin 1,000 mg daily (n = 42)
or pioglitazone 30 mg daily (n = 42). Serum concentrations of YKL-40, along with
highly sensitive C-reactive protein, indices of glycemic control and lipid
profile were measured at baseline and after 3 months. RESULTS: In the analyzed
sample (metformin = 40, pioglitazone = 42), both medications were equally
effective with regard to control of hyperglycemia, and hsCRP reduction (p >
0.05). However, metformin caused a significant decline in weight (p = 0.005), BMI
(p = 0.004), and total cholesterol levels (p = 0.028) of the patients. Metformin
also significantly reduced YKL-40 concentrations after 3 months (1.90 +/- 17 vs.
1.66 +/- 0.15 ug/L, p = 0.019). The amount of change in the pioglitazone arm did
not reach statistical significance (2.18 +/- 0.14 vs. 2.25 +/- 0.16 ug/L, p =
0.687). When compared, metformin was significantly more effective than
pioglitazone with respect to YKL-40 reduction in both univariate (p = 0.020,
effect size = 6.7%) and multivariate models (p = 0.047, effect size = 5.7%).
CONCLUSIONS: Metformin is more effective in reduction of YKL-40 concentration in
short term and the effect seems to be independent of degree of glycemic control,
or hsCRP reduction.
PMID- 25138576
TI - Telomere-centric genome repatterning determines recurring chromosome number
reductions during the evolution of eukaryotes.
AB - Whole-genome duplication (WGD) is central to the evolution of many eukaryotic
genomes, in particular rendering angiosperm (flowering plant) genomes much less
stable than those of animals. Following repeated duplication/triplication(s),
angiosperm chromosome numbers have usually been restored to a narrow range, as
one element in a 'diploidization' process that re-establishes diploid heredity.
In several angiosperms affected by WGD, we show that chromosome number reduction
(CNR) is best explained by intra- and/or inter-chromosomal crossovers to form new
chromosomes that utilize the existing telomeres of 'invaded' and centromeres of
'invading' chromosomes, the alternative centromeres and telomeres being lost.
Comparison with the banana (Musa acuminata) genome supports a 'fusion model' for
the evolution of rice (Oryza sativa) chromosomes 2 and 3, implying that the grass
common ancestor had seven chromosomes rather than the five implied by a 'fission
model.' The 'invading' and 'invaded' chromosomes are frequently homoeologs,
originating from duplication of a common ancestral chromosome and with greater
than-average DNA-level correspondence to one another. Telomere-centric CNR
following recursive WGD in plants is also important in mammals and yeast, and may
be a general mechanism of restoring small linear chromosome numbers in higher
eukaryotes.
PMID- 25138577
TI - A unique case of an indolent myometrial T-cell lymphoproliferative disorder with
phenotypic features resembling uterine CD8+ resident memory T cells.
AB - OBJECTIVE: Indolent extranodal T-cell lymphoproliferative disorders have recently
been described as new entities in the gastrointestinal tract and acral sites
displaying clonal T-cell receptor (TCR) rearrangement and nonactivated cytotoxic
CD8+ T-cell phenotypes. METHODS/RESULTS: We report a unique case of an atypical
myometrial T-cell lymphoproliferation in a 39-year-old multiparous woman, which
shares many of the features mentioned above: CD8+/TIA1+/granzyme B- phenotype,
clonal TCR rearrangement and indolent course. CONCLUSION(S): We hypothesize that
it might derive from a subset of uterine nonrecirculating CD8+ resident memory T
cells expanded after repeated exposure to allo-extravillous trophoblastic
antigen.
PMID- 25138575
TI - A therapeutic approach to treat prostate cancer by targeting Nm23-H1/h-Prune
interaction.
AB - Nm23-H1 is a metastasis suppressor gene whose overexpression is associated with
both reduced cell motility in various cancers and increased metastatic potential
in neuroblastomas, osteosarcomas, and hematological malignances. We previously
reported that Nm23-H1 exerts tumor suppressor action in prostate cancer cells and
that h-Prune, which is overexpressed in various tumor types, binds Nm23-H1.
Moreover, blockage of the Nm23-H1/h-Prune interaction with a competitive
permeable peptide (CPP) attenuates migration of breast and neuroblastoma cells.
This series of events suggests that the Nm23-H1/h-Prune protein complex regulates
cancer progression and that its specific impairment could be a new therapeutic
strategy in oncology. We found that CPP leads to inhibition of the AKT/mTORv and
NF-kBv signaling pathways and also activates apoptosis. To obtain a proof-of
concept of our hypothesis, we used a xenograft model of prostate cancer to
evaluate whether impairment of this complex using CPP results in an anti-tumoral
effect. Using a mouse orthotopic model with bioluminescent imaging, we show
evidences that CPP reduces prostate cancer metastases formation. In conclusion,
CPP being able to impair formation of the h-Prune/Nm23-H1 complex holds promise
for the treatment of prostate cancer.
PMID- 25138578
TI - Usefulness of the diameter-axial-polar nephrometry score for predicting
perioperative parameters in robotic partial nephrectomy.
AB - PURPOSE: The present study aimed to verify the association between diameter-axial
polar (DAP) nephrometry and surgical outcomes, postoperative renal function, and
perioperative complications in patients undergoing robotic partial nephrectomy
(RPN). METHODS: Diameter-axial-polar nephrometry was assessed using computed
tomography or magnetic resonance imaging on 158 patients who received RPN between
July 2007 and February 2013. Demographic data, surgical data, and perioperative
complications were recorded, and percent change between the preoperative and last
estimated glomerular filtration rate (eGFR) was determined. Linear regression
analysis was conducted to assess the relationship between the DAP sum score and
warm ischemia time (WIT), estimated blood loss (EBL), and percent decrease in
eGFR. Multivariable linear regression analysis was conducted to determine the
relationship between each DAP scoring parameter and surgical outcomes. RESULTS:
The median patient age was 50.5 years and median DAP sum score was 6. On linear
regression, the DAP sum score was associated with WIT and EBL. On multivariable
regression, all DAP parameters were associated with WIT, but the polar distance
was not associated with EBL. Patients with a higher DAP sum score showed greater
decrease in eGFR after RPN. Patients with a DAP sum score of 6 or higher had a
higher risk of major complications than those with a DAP sum score below 6.
CONCLUSIONS: Diameter-axial-polar nephrometry predicted WIT and EBL in patients
who underwent RPN. It was also associated with the decrease in eGFR and rate of
major perioperative complications, and thus can be useful for surgical planning
or patient counseling before RPN.
PMID- 25138579
TI - The impact of adding low-dose oral desmopressin therapy to tamsulosin therapy for
treatment of nocturia owing to benign prostatic hyperplasia.
AB - PURPOSE: To evaluate the efficacy and safety of adding a low-dose oral
desmopressin to tamsulosin therapy for treatment of nocturia in patients with
benign prostatic hyperplasia (BPH). METHODS: Eligible patients with BPH and
nocturia >=2/night were randomly allocated to two treatment groups; the first of
which received 3-month treatment scheme of daily oral dose of tamsulosin OCAS 0.4
mg and desmopressin MELT 60 mcg (D/T group), while the second one received
tamsulosin OCAS 0.4 mg only (T group). Patients were followed on monthly basis
and changes in the parameters from baseline to 3 months after treatment were
assessed on I-PSS/QoL questionnaire, 7-day voiding diary, urinalysis, serum
sodium, abdominal ultrasonography and uroflowmetry. RESULTS: A total of 248
patients were included within the study; 123 patients in the combined D/T group
and 125 patients in T group. The frequencies of night voids decreased by 64.3% in
D/T group compared to 44.6% in T group. The first sleep period, significantly
increased from 82.1 to 160.0 min and from 83.2 to 123.8 min in D/T and T group,
respectively; and significant differences between both groups were observed at
the end of study (p < 0.001). I-PSS, QoL score, post-void residual urine volume
and Q max were significantly improved with no statistical difference between both
groups. No serious adverse effects were reported in both groups. CONCLUSION: The
addition of low-dose oral desmopressin therapy to an alpha-blocker tamsulosin
provides effective treatment for nocturia in patients with LUTS/BPH.
PMID- 25138580
TI - Carbon nanofibers modified with heteroatoms as metal-free catalysts for the
oxidative dehydrogenation of propane.
AB - Carbon nanofibres (CNFs) were modified with B and P by an ex situ approach. In
addition, CNFs doped with N were prepared in situ using ethylenediamine as the N
and C source. After calcination, the doped CNFs were used as catalysts for the
oxidative dehydrogenation of propane. For B-CNFs, the effects of boron loading
and calcination temperature on B speciation and catalytic conversion were
studied. For the same reaction temperatures and conversions, B- and P-doped CNFs
exhibited higher selectivities to propene than pristine CNFs. The N-CNFs were the
most active but the least selective of the catalysts tested here. Our results
also show that the type of P precursor affects the selectivity to propene and
that CNFs modified using triphenylphosphine as the precursor provided the highest
selectivity at isoconversion.
PMID- 25138581
TI - Fluorescence-guided surgery improves outcome in an orthotopic osteosarcoma nude
mouse model.
AB - In order to develop a model for fluorescence-guided surgery (FGS), 143B human
osteosarcoma cells expressing red fluorescent protein (RFP) were injected into
the intramedullary cavity of the tibia in nude mice. The fluorescent areas of
residual tumors after bright-light surgery (BLS) and FGS were 10.2 +/- 2.4 mm(2)
and 0.1 +/- 0.1 mm(2) , respectively (p<0.001). The BLS-treated mice and
BLS+cisplatinum (CDDP)-treated mice had significant recurrence. In contrast, the
FGS mice and FGS+CDDP mice had very little recurring tumor growth. Disease-free
survival (DFS) in the BLS-, BLS+CDDP-, FGS-, and FGS+CDDP-treated mice was 12.5%,
37.5%, 75.0%, and 87.5%, respectively. The FGS-treated mice had a significantly
higher DFS rate than the BLS-treated mice (p=0.021). The FGS+CDDP-treated mice
had significantly higher DFS rate than the BLS+CDDP-treated mice (p=0.043).
Although chemotherapy significantly reduced multiple metastases (p=0.033), there
was no significant correlation between FGS and lung metastasis. FGS significantly
reduced the recurrence of the primary tumor but did not reduce lung metastasis.
The combination of FGS and adjuvant CDDP reduced tumor recurrence and prevented
multiple metastases. FGS and adjuvant chemotherapy should be performed as early
as possible in the disease to prevent both recurrence and metastatic development.
PMID- 25138582
TI - Diet, Physical Activity, Lifestyle Behaviors, and Prevalence of Childhood Obesity
in Irish Children: The Cork Children's Lifestyle Study Protocol.
AB - BACKGROUND: Childhood obesity is complex, and its aetiology is known to be
multifaceted. The contribution of lifestyle behaviors, including poor diet and
physical inactivity, to obesity remains unclear. Due to the current high
prevalence, childhood obesity is an urgent public health priority requiring
current and reliable data to further understand its aetiology. OBJECTIVE: The
objective of this study is to explore the individual, family, and environmental
factors associated with childhood overweight and obesity, with a specific focus
on diet and physical activity. A secondary objective of the study is to determine
the average salt intake and distribution of blood pressure in Irish children.
METHODS: A cross-sectional survey was conducted of children 8-11 years old in
primary schools in Cork, Ireland. Urban schools were selected using a probability
proportionate to size sampling strategy, and a complete sample of rural schools
from one area in Cork County were invited to participate. Information collected
included physical measurement data (anthropometric measurements, blood pressure),
early morning spot and 24 hour urine samples, a 3 day estimated food diary, and 7
days of accelerometer data. Principal- (school head) reported, parent/guardian
reported, and child-reported questionnaires collected information on lifestyle
behaviors and environmental attributes. The Cork Children's Lifestyle Study
(CCLaS) was designed by the Department of Epidemiology and Public Health in
University College Cork, Ireland in 2011 and 2012. Piloting and modification of
study methods was undertaken. Data collection took place between April 2012 and
June 2013. RESULTS: Overall, 27/46 schools and 1075/1641 children, of which 623
were boys, participated. Preliminary data analysis is underway. It is anticipated
that the results of the CCLaS study will be available in late 2014. CONCLUSIONS:
The CCLaS study has collected in-depth data on a wide range of individual,
family, social, and environmental correlates which will allow us to access
multilevel influences on childhood obesity. This study will contribute to the
evidence base by highlighting current knowledge and gaps regarding the
predominant drivers of childhood obesity.
PMID- 25138584
TI - Scaphocephaly and cranial vault reconstruction: Renier's 'H' technique.
AB - BACKGROUND: Resulting from an early fusion of the sagittal suture, scaphocephaly
(SC) is the most frequent form of all craniosynostosis and represents 40-60% of
all cases. The scope of this study is to describe the first series of Renier's
'H' technique to be applied in children with SC outside of France. METHODS: A
consecutive review is made of the medical records of children hospitalized in the
last 6 years (between March 2007 and March 2013) with isolated SC in whom
Renier's 'H' technique was performed. RESULTS: Thirteen children met the criteria
for inclusion in the study. Considering medical evaluation and parental
satisfaction, the evaluation of postsurgical cranial reconstruction was
classified as satisfactory in all cases. CONCLUSIONS: We consider the Renier's H
technique to be effective in the cranial reshaping of children with isolated SC,
with satisfactory esthetic postsurgical results.
PMID- 25138585
TI - syn-1,2-carboboration of alkynes with borenium cations.
AB - The reaction of 8-(trimethylsiloxy)quinoline (QOTMS) with BCl3 and (aryl)BCl2
forms QOBCl2 and QOBCl(aryl). The subsequent addition of stoichiometric AlCl3
follows one of two paths, dependent on the steric demands of the QO ligand and
the electrophilicity of the resulting borenium cation. The phenyl- and 5
hexylthienylborenium cations, QOBPh(+) and QOBTh(+), are formed, whereas QOBCl(+)
is not. Instead, AlCl3 preferentially binds with QOBCl2 at oxygen, forming QOBCl2
?AlCl3, rather than abstracting chloride. A modest increase in the steric demands
around oxygen, by installing a methyl group at the 7-position of the quinolato
ligand, switches the reactivity with AlCl3 back to chloride abstraction, allowing
formation of Me 2QOBCl(+). All the prepared borenium cations are highly
chlorophilic and exhibit significant interaction with AlCl4(-) resulting in an
equilibrium concentration of Lewis acidic "AlCl3" species. The presence of
"AlCl3(") species limits the alkyne substrates compatible with these borenium
systems, with reaction of [QOBPh][AlCl4 ] with 1-pentyne exclusively yielding the
cyclotrimerised product, 1,3,5-tripropylbenzene. In contrast, QOBPh(+) and
QOBTh(+) systems effect the syn-1,2-carboboration of 3-hexyne. DFT calculations
at the M06-2X/6-311G(d,p)/PCM(DCM) level confirm that the higher migratory
aptitude of Ph versus Me leads to a lower barrier to 1,2-carboboration relative
to 1,1-carboboration.
PMID- 25138586
TI - The preparation and structure of Ge3F8 - a new mixed-valence fluoride of
germanium, a convenient source of GeF2.
AB - The new binary mixed-valence fluoride of germanium, Ge3F8, has been obtained by
heating GeF4 with powdered Ge in an autoclave (390 K/4 bar/48 h). The structure
contains pyramidal Ge(II)F3 and octahedral Ge(IV)F6 units, linked by fluoride
bridges. The new compound is the missing member of the series (GeF2)n.GeF4 (n =
2, 4, or 6). Sublimation of (GeF2)n.GeF4in vacuo provides a convenient source of
GeF2 in ca. 30% overall yield.
PMID- 25138583
TI - The Lablite project: a cross-sectional mapping survey of decentralized HIV
service provision in Malawi, Uganda and Zimbabwe.
AB - BACKGROUND: In sub-Saharan Africa antiretroviral therapy (ART) is being
decentralized from tertiary/secondary care facilities to primary care. The
Lablite project supports effective decentralization in 3 countries. It began with
a cross-sectional survey to describe HIV and ART services. METHODS: 81
purposively sampled health facilities in Malawi, Uganda and Zimbabwe were
surveyed. RESULTS: The lowest level primary health centres comprised 16/20, 21/39
and 16/22 facilities included in Malawi, Uganda and Zimbabwe respectively. In
Malawi and Uganda most primary health facilities had at least 1 medical
assistant/clinical officer, with average 2.5 and 4 nurses/midwives for median
catchment populations of 29,275 and 9,000 respectively. Primary health facilities
in Zimbabwe were run by nurses/midwives, with average 6 for a median catchment
population of 8,616. All primary health facilities provided HIV testing and
counselling, 50/53 (94%) cotrimoxazole preventive therapy (CPT), 52/53 (98%)
prevention of mother-to-child transmission of HIV (PMTCT) and 30/53 (57%) ART
management (1/30 post ART-initiation follow-up only). All secondary and tertiary
level facilities provided HIV and ART services. In total, 58/81 had ART
provision. Stock-outs during the 3 months prior to survey occurred across
facility levels for HIV test-kits in 55%, 26% and 9% facilities in Malawi, Uganda
and Zimbabwe respectively; for CPT in 58%, 32% and 9% and for PMTCT drugs in 26%,
10% and 0% of facilities (excluding facilities where patients were referred out
for either drug). Across all countries, in facilities with ART stored on-site,
adult ART stock-outs were reported in 3/44 (7%) facilities compared with 10/43
(23%) facility stock-outs of paediatric ART. Laboratory services at primary
health facilities were limited: CD4 was used for ART initiation in 4/9, 5/6 and
13/14 in Malawi, Uganda and Zimbabwe respectively, but frequently only in
selected patients. Routine viral load monitoring was not used; 6/58 (10%)
facilities with ART provision accessed centralised viral loads for selected
patients. CONCLUSIONS: Although coverage of HIV testing, PMTCT and cotrimoxazole
prophylaxis was high in all countries, decentralization of ART services was
variable and incomplete. Challenges of staffing and stock management were
evident. Laboratory testing for toxicity and treatment effectiveness monitoring
was not available in most primary level facilities.
PMID- 25138587
TI - Unusual osteoporotic stress fracture: adjacent bilateral pedicle fractures.
PMID- 25138589
TI - Effect of crude extracts of selected actinomycetes on biofilm formation of A.
schindleri, M. aci, and B. cereus.
AB - Actinomycetes are well known group of gram positive bacteria for their potential
to produce antibiotics. This study sought to assess the ability of the selected
actinomycetes to control biofilm forming bacteria isolated from different dental
plaque samples. On the basis of morphological differences three out of ten
different dental plaque bacterial isolates were selected for further study. These
isolates were biochemically and genetically characterized and were identified as
Acinetobacter schinndleri, Moraxella aci, and Bacillus cereus. Antibiotic
resistant profile was measured through disc diffusion method and found that all
three isolates were moderately sensitive to ofloxacin and erythromycin and
resistant to trimethoprim. Antibacterial activity of ten different Streptomyces
strains was assessed through an agar plug and well diffusion method against three
dental biofilm forming bacteria. Two Streptomyces strains named as S.
erythrogriseus and S. labedae showed good antibacterial activity against
Moraxella and Acinetobacter strains. Ability of the four active antibiotic
producing strains to inhibit biofilm formation was assessed using microtiter
biofilm detection assay. It was found that biofilm forming ability of
Acinetobacter and Moraxella was inhibited by S. labedae an antibiotic producing
strain, while S. macrosporeus can only inhibit biofilm formation by B. cereus.
PMID- 25138588
TI - Ibrutinib inhibits collagen-mediated but not ADP-mediated platelet aggregation.
AB - The BTK (Bruton's tyrosine kinase) inhibitor ibrutinib is associated with an
increased risk of bleeding. A previous study reported defects in collagen- and
adenosine diphosphate (ADP)-dependent platelet responses when ibrutinib was added
ex vivo to patient samples. Whereas the collagen defect is expected given the
central role of BTK in glycoprotein VI signaling, the ADP defect lacks a
mechanistic explanation. In order to determine the real-life consequences of BTK
platelet blockade, we performed light transmission aggregometry in 23 patients
receiving ibrutinib treatment. All patients had reductions in collagen-mediated
platelet aggregation, with a significant association between the degree of
inhibition and the occurrence of clinical bleeding or bruising (P=0.044). This
collagen defect was reversible on drug cessation. In contrast to the previous ex
vivo report, we found no in vivo ADP defects in subjects receiving standard doses
of ibrutinib. These results establish platelet light transmission aggregometry as
a method for gauging, at least qualitatively, the severity of platelet impairment
in patients receiving ibrutinib treatment.
PMID- 25138590
TI - Effects of handling on fear reactions in young Icelandic horses.
AB - REASONS FOR PERFORMING THE STUDY: Inclusion of objective temperament tests at
practical horse breeding evaluations is of increased interest. It has been
debated whether such tests may involve human handling, since there may be
considerable differences in horses' handling experience. OBJECTIVES: To
investigate the effect of a short-term standardised handling procedure on
reactions of young horses in 2 types of fear tests (including and excluding human
handling). STUDY DESIGN: An experimental study with 3-year-old Icelandic horses
(n = 24). METHODS: Handled horses (n = 12) were trained according to a
standardised handling procedure whereas controls (n = 12) remained untrained.
Behavioural and heart rate responses in a novel object test and 2 handling fear
tests (HFTs) were measured. The HFTs were conducted with both an unknown (HFT
unknown) and a known handler (HFT-known). RESULTS: There was no effect of the
handling procedure on the horses' behavioural and heart rate responses in the
novel object test, nor in the HFT-unknown. In the HFT-known, however, handled
horses showed a significantly shorter duration of reluctance behaviour compared
with controls, whereas heart rates did not differ. Heart rates correlated
significantly between tests. CONCLUSIONS: Previous handling may affect the
behavioural fear response of horses when handled by their usual handler, whereas
this effect did not apply to an unknown handler. Heart rates appeared unaffected
by handling and may be a more reliable indicator of fearfulness. Known handlers
may 'mask' behavioural responses of horses in fear tests and thus handling by a
known handler during testing may not be appropriate for objective evaluation of
fearfulness in a practical situation.
PMID- 25138592
TI - A theoretical study of the L3 pre-edge XAS in Cu(II) complexes.
AB - L2,3 spectra of Cu(II) complexes have been simulated by means of time dependent
DFT. Besides the agreement between theory and experiment, the adopted approach
provided further insights into the use of the Cu(II) L3-edge intensity and
position to investigate the Cu-ligand symmetry-restricted covalency and the
ligand-field strength.
PMID- 25138591
TI - HIV-1 coreceptor usage in paired plasma RNA and proviral DNA from patients with
acute and chronic infection never treated with antiretroviral therapy.
AB - Although an independent evolution of viral quasispecies in different body sites
might determine a differential compartmentalization of viral variants, the aim of
this paper was to establish whether sequences from peripheral blood mononuclear
cells (PBMCs) and plasma provide different or complementary information on HIV
tropism in patients with acute or chronic infection. Tropism was predicted using
genotypic testing combined with geno2pheno (coreceptor) analysis at a 10% false
positive rate in paired RNA and DNA samples from 75 antiretroviral-naive patients
(divided on the basis of avidity index into patients with a recent or long
lasting infection). A high prevalence of R5 HIV strains (97%) was observed in
both compartments (plasma and PBMCs) in patients infected recently. By contrast,
patients with a long-lasting infection showed a quite different situation in the
two compartments, revealing more (46%) X4/DM in PBMCs than patients infected
recently (3%) (P = 0.008). As- a knowledge of viral strains in different
biological compartments might be crucial to establish a therapeutic protocol, it
could be extremely useful to detect not only viral strains in plasma, but also
viruses hidden or archived in different cell compartments to better understand
disease evolution and treatment efficacy in patients infected with HIV.
PMID- 25138594
TI - Planet-satellite nanostructures made to order by RAFT star polymers.
AB - The investigation and application of complex nanostructures requires the
hierarchical arrangement of distinct domains on a small scale. Herein, we report
a method to prepare planet-satellite arrangements using RAFT polymers. Our
approach is based on star polymers decorated with trithiocarbonate groups on
their outer periphery that attach to gold surfaces and thus provide the polymer
with the ability to connect (larger) gold nanoparticle planets with (smaller)
gold nanoparticle satellites. By adjusting the molecular weight of the polymeric
linker, nanostructures with tailored planet-satellite distances, as evidenced by
transmission electron microscopy, are obtained. This strategy offers a
straightforward way to prepare gold nanoparticle scaffolds with multiple reactive
functionalities at defined distances from the central core.
PMID- 25138595
TI - Time efficient way to calculate oxygen transfer areas and power input in
cylindrical disposable shaken bioreactors.
AB - Disposable orbitally shaken bioreactors are a promising alternative to stirred or
wave agitated systems for mammalian and plant cell cultivation, because they
provide a homogeneous and well-defined liquid distribution together with a simple
and cost-efficient design. Cultivation conditions in the surface-aerated
bioreactors are mainly affected by the size of the volumetric oxygen transfer
area (a) and the volumetric power input (P/VL ) that both result from the liquid
distribution during shaking. Since Computational Fluid Dynamics (CFD)-commonly
applied to simulate the liquid distribution in such bioreactors-needs high
computing power, this technique is poorly suited to investigate the influence of
many different operating conditions in various scales. Thus, the aim of this
paper is to introduce a new mathematical model for calculating the values of a
and P/VL for liquids with water-like viscosities. The model equations were
derived from the balance of centrifugal and gravitational forces exerted during
shaking. A good agreement was found among calculated values for a and P/VL , CFD
simulation values and empirical results. The newly proposed model enables a time
efficient way to calculate the oxygen transfer areas and power input for various
shaking frequencies, filling volumes and shaking and reactor diameters. All these
parameters can be calculated fast and with little computing power.
PMID- 25138596
TI - Spatiotemporal mapping of vascularization and innervation in the fetal murine
intestine.
AB - BACKGROUND: In mice, the intestinal tube develops from the splanchopleure before
embryonic day 9.5. Subsequent patterning of nerves and blood vessels is critical
for normal digestive function. A hierarchical branching vascular network allows
for efficient nutrient absorption, while the complex enteric nervous system
regulates intestinal motility as well as secretion, absorption, and blood flow.
Despite the well-recognized significance of these systems, the precise mechanisms
by which they develop have not been clearly established in mammals. RESULTS:
Using a novel whole-mount immunohistochemical protocol, we visualize the pattern
of intestinal neurovascular development in mice between embryonic day 10.5 and
birth. In particular, we focus on the development and remodeling of the enteric
vascular plexus, the migration and organization of enteric neural crest-derived
cells, and the integration of peripheral sympathetic nerves with the enteric
nervous system. These correlative data lead us to hypothesize a functional
interaction between migrating neural crest-derived cells and endothelial cells of
the primary capillary plexus, as well as a subsequent interaction between
developing peripheral autonomic nerves and differentiated neural crest-derived
cells. CONCLUSIONS: These studies provide useful anatomical data for continuing
investigations on the functional mechanisms underlying intestinal organogenesis.
PMID- 25138598
TI - Aerobic decolorization and degradation of Acid Orange G (AOG) by suspended
growing cells and immobilized cells of a yeast strain Candida tropicalis TL-F1.
AB - In this study, aerobic decolorization and degradation of azo dye Acid Orange G
(AOG) by both suspended growing cells and immobilized cells of a yeast strain
Candida tropicalis TL-F1 were studied. The effects of different parameters on
decolorization of AOG by both growing suspended and immobilized strain TL-F1 were
investigated. Furthermore, a possible decolorization mechanism of AOG was
proposed through analyzing metabolic intermediates using UV-vis and high
performance liquid chromatography-mass spectrometry (HPLC-MS) methods. Strain TL
F1 could decolorize AOG in both liquid and solid mediums through degradation. The
optimal conditions for decolorization with suspended growing cells of strain TL
F1 were as follows: 6-10 g/L sucrose, 5-7 g/L urea, >=6 % (v/v) inoculation size,
>=160 rpm, 35-40 degrees C, and pH 5.0-6.0; and those for immobilized cells, the
conditions were as follows: 4-6 g/L glucose, 0.2-0.4 g/L urea, 6-10 g/L (wet cell
pellets) inoculation size, >=160 rpm, 35-40 degrees C, and pH 5.0-7.0. Results
of UV-vis scanning spectra suggested that AOG was decolorized through
biodegradation, and the possible pathway was proposed through the results of HPLC
MS analysis and related literature. This is a systematic research on aerobic
decolorization and degradation of AOG by both suspended and immobilized cells of
a C. tropicalis strain.
PMID- 25138597
TI - Microbial degradation of linseed oil-based elastomer and subsequent accumulation
of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer.
AB - The microbial synthesis of environment-friendly poly(3-hydroxybutyrate--co-3
hydroxyvalerate), PHBV, has been performed by using an alkaliphilic
microorganism, Alkaliphilus oremlandii OhILAs strain (GenBank Accession number
NR_043674.1), at pH 8 and at a temperature of 30-32 degrees C through the
biodegradation of linseed oil-based elastomer. The yield of the copolymer on dry
cell weight basis is 90 %. The elastomers used for the biodegradation have been
synthesized by cationic polymerization technique. The yield of the PHBV copolymer
also varies with the variation of linseed oil content (30-60 %) in the elastomer.
Spectroscopic characterization ((1)H NMR and FTIR) of the accumulated product
through biodegradation of linseed oil-based elastomers indicates that the
accumulated product is a PHBV copolymer consisting of 13.85 mol% of 3
hydroxyvalerate unit. The differential scanning calorimetry (DSC) results
indicate a decrease in the melting (T m) and glass transition temperature (T g)
of PHBV copolymer with an increase in the content of linseed oil in the
elastomer, which is used for the biodegradation. The gel permeation
chromatography (GPC) results indicate that the weight average molecular weight (M
w) of PHBV copolymer decreases with an increasing concentration of linseed oil in
the elastomer. The surface morphology of the elastomer before and after
biodegradation is observed under scanning electron microscope (SEM) and atomic
force microscope (AFM); these results indicate about porous morphology of the
biodegraded elastomer.
PMID- 25138599
TI - Crystal structure of Talaromyces cellulolyticus (formerly known as Acremonium
cellulolyticus) GH family 11 xylanase.
AB - Talaromyces cellulolyticus (formerly known as Acremonium cellulolyticus) is one
of the mesophilic fungi that can produce high levels of cellulose-related enzymes
and are expected to be used for the degradation of polysaccharide biomass. In
silico analysis of the genome sequence of T. cellulolyticus detected seven open
reading frames (ORFs) showing homology to xylanases from glycoside hydrolase (GH)
family 11. The gene encoding the GH11 xylanase C (TcXylC) with the highest
activity was used for overproduction and purification of the recombinant enzyme,
permitting solving of the crystal structure to a resolution of 1.98 A. In the
asymmetric unit, two kinds of the crystal structures of the xylanase were
identified. The main structure of the protein showed a beta-jelly roll structure.
We hypothesize that one of the two structures represents the open form and the
other shows the close form. The changing of the flexible region between the two
structures is presumed to induce and accelerate the enzyme reaction. The
specificity of xylanase toward the branched xylan is discussed in the context of
this structural data and by comparison with the other published structures of
xylanases.
PMID- 25138600
TI - Effects of temperature and substrate concentration on lipid production by
Chlorella vulgaris from enzymatic hydrolysates of lipid-extracted microalgal
biomass residues (LMBRs).
AB - The enzymatic hydrolysates of the lipid-extracted microalgal biomass residues
(LMBRs) from biodiesel production were evaluated as nutritional sources for the
mixotrophic growth of Chlorella vulgaris and lipid production at different
temperature levels and substrate concentrations. Both parameters had a
significant effect on cell growth and lipid production. It was observed that C.
vulgaris could grow mixotrophically in a wide range of temperatures (20~35
degrees C). The optimal temperature for cell growth and lipid accumulation of the
mixotrophic growth of C. vulgaris was between 25 and 30 degrees C. The neutral
lipids of the culture at 25 degrees C accounted for as much as 82 % of the total
lipid content in the microalga at culture day 8. Fatty acid composition analysis
showed that the increase of saturated fatty acids was proportional to the
increase in temperature. The maximum biomass concentration of 4.83 g/L and the
maximum lipid productivity of 164 mg/L/day were obtained at an initial total
sugar concentration of 10 g/L and an initial total concentration of amino acids
of 1.0 g/L but decreased at lower and higher substrate concentrations. The
present results show that LMBRS could be utilized by the mixotrophic growth of C.
vulgaris for microalgal lipid production under the optimum temperature and
substrate concentration.
PMID- 25138601
TI - Optimizing cultivation strategies for robust algal growth and consequent removal
of inorganic nutrients in pretreated livestock effluent.
AB - Dilution was employed as a pretreatment strategy to increase light transmittance
and decrease ammonia toxicity in piggery effluent prior to the cultivation of
microalgae. The dilution effect was quantitatively determined based on both the
maximum specific nutrient consumption rate and the maximum growth coefficient to
minimize the usage of diluent. The biomass productivity of microalgae was also
evaluated to select the best species among the five different candidates
examined. A 20-fold dilution of piggery wastewater resulted in decreased
chromaticity (584 mg Pt-Co L(-1)) and total nitrogen (76 mg L(-1)), on which the
microalgae cultivation was more effective for an algal growth compared to the
other dilution factors. If the initial cell concentration of Scenedesmus
quadricauda increased, the production of biomass tended to improve. Robust growth
and harvesting of S. quadricauda were achieved, and the associated consistent
removal of inorganic nutrients was accomplished during the semi-continuous
cultivation of the best species.
PMID- 25138602
TI - Preface.
PMID- 25138603
TI - Disseminated cysticercosis revealed by subcutaneous nodules in a migrant from
Cameroon.
PMID- 25138604
TI - Twin-reversed arterial perfusion sequence in a triple monochorionic pregnancy
with two direct pump fetuses results in significant cyclic Doppler waveform.
AB - We report a case of a twin-reversed arterial perfusion (TRAP) sequence
complication in monochorionic triplets, in which both normal fetuses were
directly connected to the umbilical cord of the acardiac fetus, thus both acting
as a pump twin. Doppler ultrasound showed a significant waveform pattern with two
superposed systolic waveforms in the same vessel. After birth, placental findings
confirmed the existence of two direct pump twins. The Doppler pattern described
here may be of help to distinguish the existence of two pump twins in a triplet
monochorionic pregnancy with TRAP.
PMID- 25138605
TI - Spironolactone in the treatment of central serous chorioretinopathy - a case
series.
AB - BACKGROUND: The pathogenesis of central serous chorioretinopathy (CSC) is still
poorly understood. An animal model of CSC proved that the mineralocorticoid
receptor [1] of the choroid also plays a role in CSC. Since there is still no
evidence-based therapy for non-self-limiting CSC, this case series evaluates the
effect of oral spironolactone in CSC patients. METHODS: In this interventional,
uncontrolled, prospective case series, we present 18 consecutive CSC patients.
Patients were treated with spironolactone 25 mg twice daily (Spironolacton AL(r)
50 mg, ALIUD PHARMA) for up to 12 weeks. Follow-up examinations with BCVA, OCT,
and EDI-OCT were performed at 1, 2, and 3 months after starting the treatment.
Main outcome measure was a change of subretinal fluid (SRF) (in micrometers)
measured by optical coherence tomography. Secondary outcome was a change in
central retinal thickness (CRT) (in micrometers) measured by OCT and a change in
BCVA. RESULTS: The subretinal fluid (SRF; mean) decreased from 219 MUm (baseline)
to 100 MUm (visit 3) (difference 119 MUm). Total central retinal thickness (CRT;
mean) decreased from 405 MUm before treatment (baseline) to 287 MUm after
treatment (difference 118 MUm). The BCVA (in logMAR; mean) increased from 0.32 at
baseline to 0.20 at visit 3. CONCLUSION: Our case series could confirm a positive
influence of spironolactone on the course CSC. Longer follow-up with a larger
number of cases could provide more data about the long-term efficiency,
recurrences, and safety of this well-tolerated and non-invasive treatment option
of CSC.
PMID- 25138606
TI - Cytomegalovirus anterior uveitis: long-term follow-up of immunocompetent
patients.
AB - BACKGROUND: We aimed to report on the clinical findings and long-term prognosis
of patients with cytomegalovirus (CMV) anterior uveitis. METHODS: This was a
retrospective observational study on 15 immunocompetent patients with CMV
anterior uveitis and a follow-up longer than 24 months (mean: 62.1 +/- 28.5
months). RESULTS: Uveitis was unilateral and hypertensive in all cases, with
acute relapsing having the characteristics of Posner-Schlossman syndrome in nine
(60 %) and chronic in nine patients (40 %), three of whom were clinically
classified as Fuchs' heterocromic iridocyclitis (20 %). All patients received
topical antiviral and corticosteroid therapy, with six patients also receiving
systemic therapy with valganciclovir or acyclovir. The mean number of uveitis
relapses significantly decreased, before and after anti-CMV therapy, from 0.23 +/
0.17 to 0.03 +/- 0.03 (p < 0.001), without significant differences among
patients treated with topical therapy alone or combined topical and systemic
therapy. Cataracts developed in nine out of 13 patients (69.2 %). A chronic raise
in intraocular pressure (IOP) was found in 13 patients (86.6 %), with nine
requiring surgery (60 %). At the end of the follow-up, all patients had a
quiescent uveitis, with ten of them requiring topical low dose steroid therapy
(66.6 %) and combined with systemic acyclovir in four cases. Eight patients (53.3
%) were on antiglaucomatous therapy. The last mean IOP value was 14.9 +/- 3.6
mmHg (range 8-21 mmHg), and visual acuity was 0.89 +/- 0.21. CONCLUSIONS: CMV
associated anterior uveitis has a fairly good long-term visual prognosis.
Antiviral therapy can reduce the frequency of relapses, but cataracts and a
chronic raise in IOP are frequent complications often requiring a surgical
approach.
PMID- 25138608
TI - Aberrant drug-related behaviors: a qualitative analysis of medical record
documentation in patients referred to an HIV/chronic pain clinic.
AB - BACKGROUND: Due to rising rates of opioid addiction and overdose among
individuals on chronic opioid therapy, aberrant drug-related behaviors (ADRBs)
are an important and challenging issue. Our objective was to qualitatively
investigate the documentation of ADRBs in the medical record. METHODS: Manually
abstracted provider notes from an HIV primary care clinic were analyzed using
content analysis methods. RESULTS: Categories of ADRBs identified included
patients requesting opioids, obtaining nonprescribed opioids, and becoming
emotional about opioids. We also identified several types of provider language
used when documenting ADRBs, including purely descriptive language and emotional
language such as labeling, frustration, and concern, and responses such as
setting conditions for opioid prescription and action-oriented language.
CONCLUSIONS: The impact of including emotional language in the medical record is
unknown. Development of instruments that can be used to facilitate ADRB
documentation, as well as evidence-based approaches to addressing ADRBs, is
needed.
PMID- 25138609
TI - Cutaneous manifestations of methotrexate-associated lymphoproliferative
disorders: report of two cases and a review of the literature.
PMID- 25138610
TI - Heart failure as a risk factor for diabetes mellitus.
AB - BACKGROUND: Diabetes mellitus (DM) is a well-recognized risk factor for heart
failure (HF). We hypothesized that HF also increases the risk for DM. OBJECTIVE:
We explored the hypothesis that HF is a risk factor for DM. METHODS: The
Cardiovascular Health Study was a prospective cohort study of cardiovascular risk
in ambulatory older adults. We used a limited-access dataset provided by the
National Heart, Lung and Blood Institute. The impact of HF at baseline on DM
after 3 or 4 years was examined in a cohort of 3,748 nondiabetic participants
aged >=65 years. The magnitude and significance of the association were evaluated
using logistic regression models. Analyses were performed with and without
adjustment for confounders and separately among subjects with normal and impaired
fasting glucose at baseline. RESULTS: Among subjects with normal fasting glucose
at baseline, HF significantly increased the odds of developing impaired fasting
glucose after 3 or 4 years [odds ratio (OR) 2.18, 95% confidence interval (CI)
1.03-4.61, p = 0.043] or overt DM (OR 4.78, 95% CI 1.84-12.4, p < 0.001). After
adjusting for demographic and biomedical factors, HF remained significantly
associated with a worsening DM status (OR 2.43, 95% CI 1.38-4.29, p = 0.002).
CONCLUSIONS: In the elderly population, the presence of HF more than doubles the
incidence of DM within a few years. This association remains significant when
adjusting for age, gender and cardiovascular comorbidities.
PMID- 25138607
TI - Multi-omic integrated networks connect DNA methylation and miRNA with skeletal
muscle plasticity to chronic exercise in Type 2 diabetic obesity.
AB - Epigenomic regulation of the transcriptome by DNA methylation and
posttranscriptional gene silencing by miRNAs are potential environmental
modulators of skeletal muscle plasticity to chronic exercise in healthy and
diseased populations. We utilized transcriptome networks to connect exercise
induced differential methylation and miRNA with functional skeletal muscle
plasticity. Biopsies of the vastus lateralis were collected from middle-aged
Polynesian men and women with morbid obesity (44 kg/m(2) +/- 10) and Type 2
diabetes before and following 16 wk of resistance (n = 9) or endurance training
(n = 8). Longitudinal transcriptome, methylome, and microRNA (miRNA) responses
were obtained via microarray, filtered by novel effect-size based false discovery
rate probe selection preceding bioinformatic interrogation. Metabolic and
microvascular transcriptome topology dominated the network landscape following
endurance exercise. Lipid and glucose metabolism modules were connected to:
microRNA (miR)-29a; promoter region hypomethylation of nuclear receptor factor
(NRF1) and fatty acid transporter (SLC27A4), and hypermethylation of fatty acid
synthase, and to exon hypomethylation of 6-phosphofructo-2-kinase and Ser/Thr
protein kinase. Directional change in the endurance networks was validated by
lower intramyocellular lipid, increased capillarity, GLUT4, hexokinase, and
mitochondrial enzyme activity and proteome. Resistance training also lowered
lipid and increased enzyme activity and caused GLUT4 promoter hypomethylation;
however, training was inconsequential to GLUT4, capillarity, and metabolic
transcriptome. miR-195 connected to negative regulation of vascular development.
To conclude, integrated molecular network modelling revealed differential DNA
methylation and miRNA expression changes occur in skeletal muscle in response to
chronic exercise training that are most pronounced with endurance training and
topographically associated with functional metabolic and microvascular plasticity
relevant to diabetes rehabilitation.
PMID- 25138611
TI - Comparison of the long-term skeletal stability between a biodegradable and a
titanium fixation system following BSSO advancement - a cohort study based on a
multicenter randomised controlled trial.
AB - Biodegradable fixation systems could reduce or eliminate the problems associated
with removal of titanium plates. A multicenter randomised controlled trial (RCT)
was performed in the Netherlands from December 2006-July 2009, and originally 230
injured and orthognathic patients were included. The patients were randomly
assigned to either a titanium control group (KLS Martin) or to a biodegradable
test group (Inion CPS). The aim of the present study was to compare the long-term
skeletal stability of advancement bilateral sagittal split osteotomies (BSSO) of
a biodegradable system and a titanium system. Only patients from the original RCT
who were at least 18 years old and who had a BSSO advancement osteotomy were
included. Those who had simultaneous Le Fort I osteotomy or genioplasty were
excluded. Analysis of skeletal stability was made by digital tracing of lateral
cephalograms. Long-term skeletal stability in BSSO advancement did not differ
significantly between patients treated with biodegradable plates and screws and
those treated with titanium plates and screws. Given the comparable amount of
relapse, the general use of Inion CPS in the treatment of BSSO advancement should
not be discouraged. On the basis of other properties a total picture of the
clinical use can be obtained; the short-term stability, the intraoperative
switches, the number of plates removed and cost-effectiveness. Trial registration
of original RCT: http://www.controlled-trials.com; ISRCTN 44212338.
PMID- 25138612
TI - Biomechanical investigation of naso-orbitoethmoid trauma by finite element
analysis.
AB - Naso-orbitoethmoid fractures account for 5% of all facial fractures. We used data
derived from a white 34-year-old man to make a transient dynamic finite element
model, which consisted of about 740 000 elements, to simulate fist-like impacts
to this anatomically complex area. Finite element analysis showed a pattern of
von Mises stresses beyond the yield criterion of bone that corresponded with
fractures commonly seen clinically. Finite element models can be used to simulate
injuries to the human skull, and provide information about the pathogenesis of
different types of fracture.
PMID- 25138613
TI - Leucocyte-rich and platelet-rich fibrin for the treatment of bisphosphonate
related osteonecrosis of the jaw: a prospective feasibility study.
AB - Our aim was to assess the feasibility of using leucocyte-rich and platelet-rich
fibrin (L-PRF) for the treatment of bisphosphonate-related osteonecrosis of the
jaw (BRONJ) in a single group study. After treatment with L-PRF, the response of
each patient was recorded 1 month and 4 months postoperatively. Further
assessments were made of the site, stage, concentration of c-terminal crosslinked
telopepide of type 1 collagen, and actinomycosis. Among the total of 34 patients,
26 (77%) showed complete resolution, 6 (18%) had delayed resolution, and 2 (6%)
showed no resolution. There was a significant association between the response to
treatment and the stage of BRONJ (p=0.002) but no other significant associations
were detected. This study has shown that it is feasible to use L-PRF for the
treatment of BRONJ, but the effectiveness cannot be judged with this study
design. Randomised prospective trials are needed to confirm this.
PMID- 25138614
TI - Knee arthrodesis as limb salvage for complex failures of total knee arthroplasty.
AB - Patients with multiple failures of total knee arthroplasty (TKA) are challenging
limb salvage cases. Twenty one patients over the last 10 years were referred to
our service for knee fusion by arthroplasty surgeons who felt they were not
candidates for revision TKA. Active infection was present in 76.2% and total bone
loss averaged 6.6 cm. Lengthening was performed in 7/22 patients. Total time in
Ilizarov frames was 9 months, with 93.3% union. Patients treated with IM fusion
nails had 100% union. Average LLD increased from 3.6 to 4.5 cm following
intervention, while those with concurrent lengthening improved to 1.6 cm.
Findings suggest that bone loss and the soft-tissue envelope dictate knee fusion
method, and multiple techniques may be needed. A treatment algorithm is
presented.
PMID- 25138615
TI - Relationship between mechanical axis-derived and anatomic landmark-derived
femoral rotation in TKA: a three-dimensional CT study.
AB - We sought to determine the relationship between the mechanical axis-derived and
the anatomic landmark-derived femoral rotational axes using three dimensional
computed tomographic images of 20 lower extremities. The mechanical axis-derived
femoral rotational axis was created on the distal articular surface of the femur
using coronal mechanical limb axis and the reconstructed images of the femur.
Then, we measured the angular difference between mechanical axis-derived and
anatomic landmark-derived femoral rotational axes. The mechanical axis-derived
femoral rotational axis was externally rotated with a mean of 2.2 degrees
(range, 0 to 4.7 degrees ; SD, 1.0) compared with the surgical epicondylar axis.
Our findings should be considered to obtain a proper femoral rotational axis in
total knee arthroplasty.
PMID- 25138617
TI - Shame if you do--shame if you don't: women's experiences of infant feeding.
AB - Emotions such as guilt and blame are frequently reported by non-breastfeeding
mothers, and fear and humiliation are experienced by breastfeeding mothers when
feeding in a public context. In this paper, we present new insights into how
shame-related affects, cognitions and actions are evident within breastfeeding
and non-breastfeeding women's narratives of their experiences. As part of an
evaluation study of the implementation of the UNICEF UK Baby Friendly Initiative
Community Award within two primary (community based) care trusts in North West
England, 63 women with varied infant feeding experiences took part in either a
focus group or an individual semi-structured interview to explore their
experiences, opinions and perceptions of infant feeding. Using a framework
analysis approach and drawing on Lazare's categories of shame, we consider how
the nature of the event (infant feeding) and the vulnerability of the individual
(mother) interact in the social context to create shame responses in some
breastfeeding and non-breastfeeding mothers. Three key themes illustrate how
shame is experienced and internalised through 'exposure of women's bodies and
infant feeding methods', 'undermining and insufficient support' and 'perceptions
of inadequate mothering'. The findings of this paper highlight how breastfeeding
and non-breastfeeding women may experience judgement and condemnation in
interactions with health professionals as well as within community contexts,
leading to feelings of failure, inadequacy and isolation. There is a need for
strategies and support that address personal, cultural, ideological and
structural constraints of infant feeding.
PMID- 25138618
TI - Exploring the myths of morphine in cancer: views of the general practice
population.
AB - BACKGROUND: Morphine is widely used in cancer care, and understanding the
concerns and perceptions of patients, family and friends is vital to managing
pain and distress effectively. The 'myths of morphine' have frequently been
discussed in medical literature, yet the extent to which such views are held is
not clear. This qualitative project explores the perceptions and attitudes of the
wider community towards morphine use in cancer care, to understand this
'mythology' according to those who in the future may themselves require its use.
METHODS: Semi-structured interviews were held with patients presenting to a
metropolitan general practice clinic in Melbourne, Australia. A grounded theory
framework underpinned the data collection and thematic analysis undertaken.
RESULTS: Interviewees (15) were aged 24-81, with a variety of experiences with
cancer care and previous morphine use. Interviewees were highly supportive of
morphine use in cancer care, with this attitude founded on the perceived severity
of cancer pain and the powerful nature of morphine. They described a number of
reasons morphine may be used in cancer care: to treat pain, to enable peace and
also as a treatment for cancer. CONCLUSION: The public view of morphine to emerge
from this study is markedly different from that discussed in the myths of
morphine. It is viewed as a medication that has the ability to provide peace and
control both pain and the course of cancer. The participants in this study
described a wish for greater involvement in pain control decisions, perceiving
morphine as a facilitator rather than a barrier to good cancer care.
PMID- 25138619
TI - 'Prostate Abscess' as the Initial Manifestation of Granulomatosis with
Polyangiitis (Wegener's Granulomatosis).
AB - Prostatic involvement in granulomatosis with polyangiitis (GWP), formerly known
as Wegener's granulomatosis, is rare, mostly arising in the context of systemic
involvement. Prostatic involvement as the first manifestation of this systemic
disease is exceptionally rare. We hereby present the case of a 41-year-old male
patient who underwent transurethral prostate resection for what was initially
diagnosed as suppurative, focally necrotizing prostatitis. Prolonged
postoperative fever that did not respond to various treatments, as well as the
subsequent appearance of a left pleural effusion, a left upper pulmonary lobe
lesion and cutaneous nodules, led to a reevaluation of histological slides which,
along with the determination of serum c-ANCA/anti-PR3 antibody levels,
established the diagnosis of GWP. Physicians, and especially urologists and
infectious diseases specialists, should be aware of this rare association and
consider GWP in the event of nonresolving prostatitis, especially when
characteristic symptoms from other systems appear.
PMID- 25138616
TI - A systematic review of the quality of reporting in published smoking cessation
trials for pregnant women: an explanation for the evidence-practice gap?
AB - BACKGROUND: To facilitate translation of evidence into clinical practice, it is
critical that clear, specific, and detailed information about interventions is
provided in publications to promote replication, appropriate aggregation in meta
analysis, and implementation. This study examined whether twenty elements of
interventions deemed essential for such translational application were reported
in sufficient detail in smoking cessation trials with pregnant women. METHODS:
Searches of electronic databases using MeSH terms and keywords identified peer
reviewed English language studies published between 2001 and 2012. Eligible
studies reported a smoking cessation intervention targeted at pregnant women and
met Cochrane's Effective Practice and Organization of Care group study design
criteria. Each intervention arm of eligible studies was assessed against the
developed twenty criteria. RESULTS: Thirty relevant studies reported the findings
of 45 intervention arms. The mode of delivery of the intervention was reported in
100% of intervention arms. Other well-reported criteria included reporting of the
provider who delivered the intervention (96%), sample characteristics (80%), and
the intervention setting (80%). Criteria not reported adequately included care
provided to women who relapse (96% not reported), details about training given to
providers (77% not reported), and the method of quit advice advised (76% not
reported). No studies reported 100% of relevant criteria. CONCLUSIONS: Current
standards of reporting of intervention content and implementation are suboptimal.
The use of smoking cessation specific checklists for reporting of trials,
standard reporting using behaviour change taxonomies, and the publication of
protocols as supplements should be considered as ways of improving the
specificity of reporting.
PMID- 25138620
TI - An international consensus algorithm for management of chronic postoperative
inguinal pain.
AB - PURPOSE: Tension-free mesh repair of inguinal hernia has led to uniformly low
recurrence rates. Morbidity associated with this operation is mainly related to
chronic pain. No consensus guidelines exist for the management of this condition.
The goal of this study is to design an expert-based algorithm for diagnostic and
therapeutic management of chronic inguinal postoperative pain (CPIP). METHODS: A
group of surgeons considered experts on inguinal hernia surgery was solicited to
develop the algorithm. Consensus regarding each step of an algorithm proposed by
the authors was sought by means of the Delphi method leading to a revised expert
based algorithm. RESULTS: With the input of 28 international experts, an
algorithm for a stepwise approach for management of CPIP was created. 26
participants accepted the final algorithm as a consensus model. One participant
could not agree with the final concept. One expert did not respond during the
final phase. CONCLUSION: There is a need for guidelines with regard to management
of CPIP. This algorithm can serve as a guide with regard to the diagnosis,
management, and treatment of these patients and improve clinical outcomes. If an
expectative phase of a few months has passed without any amelioration of CPIP, a
multidisciplinary approach is indicated and a pain management team should be
consulted. Pharmacologic, behavioral, and interventional modalities including
nerve blocks are essential. If conservative measures fail and surgery is
considered, triple neurectomy, correction for recurrence with or without
neurectomy, and meshoma removal if indicated should be performed. Surgeons less
experienced with remedial operations for CPIP should not hesitate to refer their
patients to dedicated hernia surgeons.
PMID- 25138621
TI - Secondary inguinal hydatidosis mimicking irreducible inguinal hernia: report of a
rare case.
AB - Peritoneal hydatidosis secondary to liver hydatid disease is not uncommon but
peritoneal hydatidosis herniating to the inguinal canal is rare, with fewer than
five cases reported in the literature. We describe a 54-year-old man who
presented with a progressively enlarging soft, cystic swelling in the right
inguinal region. Clinical examination suggestive of irreducible right inguinal
hernia and ultrasonography revealed it to be a cystic swelling within the hernial
sac. The swelling was excised en bloc and open mesh hernioplasty was performed.
Cyst biopsy revealed hydatid disease; hence, the patient was put on adjunctive
albendazole chemotherapy for 3 months.
PMID- 25138622
TI - Ultrasound scoring in combination with ultrasound elastography for
differentiating benign and malignant thyroid nodules.
AB - OBJECTIVE: The aim of this study was to evaluate the value of ultrasound scores
obtained by conventional ultrasonography and ultrasound elastography in the
differentiation of benign and malignant thyroid nodules in Chinese patients.
METHODS: This study included 297 patients who were referred for surgery for
compressive symptoms or suspicion of malignancy. Five hundred and twelve thyroid
nodules were examined by ultrasonography. The final diagnosis was based on
histological findings. A seven-point ultrasound scoring system based on
conventional ultrasonography and a five-point scoring system based on ultrasound
elastography were applied independently or in combination. The receiver operating
characteristic (ROC) curves were graphed, and the areas under the curves (AUCs)
were compared using the chi(2) -test. RESULTS: Solid composition, hypo-echoic
appearance, an irregular or blurred margin, an aspect ratio >=1, intranodular
blood flow and presence of microcalcifications were significant predictors of
malignant thyroid nodules. The AUC (95% CI) was 0.9067 (0.8817-0.9318) for the
ultrasound scores based on conventional ultrasonography and 0.9080 (0.8842
0.9317) for the elasticity scores. The combination of these two scoring systems
provided good accuracy with an AUC (95% CI) of 0.9415 (0.9223-0.9606), which was
significantly higher than that obtained with the conventional ultrasound scores
(chi(2) = 36.03, P < 0.001) or the elasticity scores (chi(2) = 12.80, P <
0.001) individually. When we set the cut-point to >=5, the sensitivity and
specificity were 85.22% and 87.38%, respectively. CONCLUSIONS: Elastography in
combination with conventional ultrasonography is a promising imaging-based
approach that can assist in the differential diagnosis of thyroid cancer.
PMID- 25138624
TI - Evaluation of elastic bands for lower extremity resistance training in adults
with and without musculo-skeletal pain.
AB - Therapists commonly use elastic bands in resistance exercises during
rehabilitation of smaller muscles, such as in the shoulder. However, the
effectiveness has not yet been investigated for larger muscle groups. This study
investigates muscle activity during lower extremity exercises. Electromyographic
(EMG) activity of 10 muscles was measured in 24 women and 18 men during lunges
with elastic resistance, lunges with dumbbells, and unilateral leg press in
machine using 10 repetition maximum loadings, and normalized to maximal voluntary
isometric contraction EMG. Lunges with dumbbells and leg press showed higher
activity than lunges with elastic resistance for the vasti and rectus femoris (P
< 0.01), whereas lunges with elastic resistance showed higher activity of gluteus
maximus, hamstrings, and erector spinae (P < 0.01). Gender, age, and pain in the
knees and hip did not influence these findings. However, pain in the lower back
decreased muscular activity of the gluteus maximus and vastus medialis (P <
0.01). Lunges with elastic resistance induce high levels of muscle activity in
all the large muscle groups at the hip, knee, and back. Importantly, the
efficiency of these exercises was equally high regardless of gender, age, and
pain in the knees and hip, whereas pain in the lower back led to altered
activation strategies.
PMID- 25138625
TI - Effects of garlic extract on spreading depression: In vitro and in vivo
investigations.
AB - OBJECTIVES: The potential use of garlic for prevention and treatment of different
types of headaches has been suggested by several medieval literatures. Cortical
spreading depression (CSD), a propagating wave of neuroglial depolarization, was
established as a target for anti-migraine drugs. This study was designed to
investigate the effect of garlic extract on CSD in adult rats. METHODS: CSD was
induced by KCl microinjection in the somatosensory cortex. The effects of five
different concentrations of garlic oil (1-500 MUl/l) were tested on different
characteristic features of CSD in necocortical slices. In in vivo experiments,
the effects of garlic oil on electrophysiological and morphological changes
induced by CSD were investigated. RESULTS: Garlic oil in a dose-dependent manner
decreased the amplitude of CSD but not its duration and velocity in neocortical
brain slices. Garlic oil at concentration of 500 MUl/l reversibly reduced the
amplitude of the field excitatory post-synaptic potentials and inhibited
induction of long-term potentiation in the third layer of neocortical slices. In
in vivo studies, systemic application of garlic oil (1 ml/l) for three
consecutive days reduced the amplitude and repetition rate of CSD. Garlic oil
also prevented of CSD-induced reactive astrocytosis in the neocortex. DISCUSSION:
Garlic oil suppresses CSD, likely via inhibition of synaptic plasticity, and
prevents its harmful effects on astrocyte. Further studies are required to
identify the exact active ingredient(s) of garlic oil that inhibit CSD and may
have the potential to use in treatment of CSD-related disorders.
PMID- 25138626
TI - "There is iron and iron..." Burkinabe women's perceptions of iron
supplementation: a qualitative study.
AB - Most pregnant women in Burkina Faso are iron deficient and many are anemic. This
study assessed women's understanding of anemia and the role of iron in preventing
and treating this condition. A qualitative study was conducted within a
randomized controlled trial of weekly iron supplementation in a rural malaria
endemic area. Focus groups with women of similar age, parity, and marital status
took place in 12 of 24 study villages. Two additional focus groups were conducted
with female field workers. Tape-recorded transcripts were translated into French
and analyzed using Framework analysis. Anemia, for which no Moore term or
traditional treatment for anemia was evident, was described in terms of blood
volume. Moderate blood loss (diminished blood) could be easily replaced by eating
well and was not considered serious. Massive blood loss (finished blood) was a
rare, life-threatening illness. Iron tablets could increase blood volume and help
women withstand massive blood loss at delivery, but for the latter, transfusion
was indicated. Women had no knowledge of iron's role and did not readily concede
that iron supplements contained elemental iron. Neither adolescents nor field
workers were convinced of the benefits of supplementing non-pregnant adolescents,
who were incorrectly considered to be at low risk of anemia. Young women's
knowledge of anemia did not provide an adequate explanatory framework to motivate
anemia prevention. Improving information on the role of iron is especially
important for adolescent girls who may be incorrectly considered at low risk of
anemia as they have not yet experienced pregnancy.
PMID- 25138627
TI - Bone density among infants of gestational diabetic mothers and macrosomic
neonates.
AB - Decreased bone density has been found among infants of diabetic mothers and among
large-for-gestational-age newborns. To evaluate which etiologies (physical or
metabolic effect) have the greatest impact on neonatal bone density. A case
control study was conducted that included two study groups: one comprising 20
appropriate-for-gestational-age (AGA) infants of gestational diabetic mothers
(IGDM) and matched controls, and the other comprising 20 macrosomic infants
(birth weight > 4 kg) and matched controls. Bone density was examined along the
tibia bone using quantitative ultrasound that measured speed of sound. Bone
density among the group of macrosomic infants was significantly lower than among
the control group (2,976 vs. 3,120 m/s respectively, p < 0.005). No differences
in bone density were found between infants of diabetic mothers and their controls
(3,005 vs. 3,043 m/s respectively, p = 0.286). Low bone density was predicted
only by birth weight (for every increase of 100 g) (OR 1.148 [CI 1.014-1.299], p
= 0.003). Bone density was found to be low among macrosomic newborn infants,
whereas among AGA-IGDM infants bone density was similar to that of the control
group. These findings strengthen the hypothesis that reduced fetal movements
secondary to fetal macrosomia constitute the mechanism for reduced bone density.
PMID- 25138628
TI - Pathways community care coordination in low birth weight prevention.
AB - The evidence is limited on the effectiveness of home visiting care coordination
in addressing poor birth outcome, including low birth weight (LBW). The Community
Health Access Project (CHAP) utilizes community health workers (CHWs) to identify
women at risk of having poor birth outcomes, connect them to health and social
services, and track each identified health or social issue to a measurable
completion. CHWs are trained individuals from the same highest risk communities.
The CHAP Pathways Model is used to track each maternal health and social service
need to resolution and CHWs are paid based upon outcomes. We evaluated the impact
of the CHAP Pathways program on LBW in an urban Ohio community. Women
participating in CHAP and having a live birth in 2001 through 2004 constituted
the intervention group. Using birth certificate records, each CHAP birth was
matched through propensity score to a control birth from the same census tract
and year. Logistic regression was used to examine the association of CHAP
participation with LBW while controlling for risk factors for LBW. We identified
115 CHAP clients and 115 control births. Among the intervention group there were
seven LBW births (6.1 %) compared with 15 (13.0 %) among non-CHAP clients. The
adjusted odds ratio for LBW was 0.35 (95 % confidence interval, 0.12-0.96) among
CHAP clients. This study provides evidence that structured community care
coordination coupled with tracking and payment for outcomes may reduce LBW birth
among high-risk women.
PMID- 25138629
TI - New evidence on breastfeeding and postpartum depression: the importance of
understanding women's intentions.
AB - This study aimed to identify the causal effect of breastfeeding on postpartum
depression (PPD), using data on mothers from a British survey, the Avon
Longitudinal Study of Parents and Children. Multivariate linear and logistic
regressions were performed to investigate the effects of breastfeeding on
mothers' mental health measured at 8 weeks, 8, 21 and 32 months postpartum. The
estimated effect of breastfeeding on PPD differed according to whether women had
planned to breastfeed their babies, and by whether they had shown signs of
depression during pregnancy. For mothers who were not depressed during pregnancy,
the lowest risk of PPD was found among women who had planned to breastfeed, and
who had actually breastfed their babies, while the highest risk was found among
women who had planned to breastfeed and had not gone on to breastfeed. We
conclude that the effect of breastfeeding on maternal depression is extremely
heterogeneous, being mediated both by breastfeeding intentions during pregnancy
and by mothers' mental health during pregnancy. Our results underline the
importance of providing expert breastfeeding support to women who want to
breastfeed; but also, of providing compassionate support for women who had
intended to breastfeed, but who find themselves unable to.
PMID- 25138630
TI - Stiffness versus prestress relationship at subcellular length scale.
AB - Local intracellular variations of cell mechanical properties, which are essential
for vital cellular functions, have not been well characterized and are poorly
understood. Here, we used results from our previous biomechanical imaging study
to obtain relationships between intracellular shear modulus and prestress. We
found that the subcellular shear modulus vs. prestress relationships exhibited
positive linear correlations, consistent with previously observed behaviors at
the whole cell and tissue levels. This, in turn, suggests that the prestress may
be a unifying factor that determines material properties of living matter at
different length scales.
PMID- 25138632
TI - Intoxication by angel's trumpet: case report and literature review.
AB - BACKGROUND: Brugmansia, commonly referred to as angel's trumpet (AT), has been
become popular in Korea as an ornamental shrub. However, it is not generally
known by the public that this plant contains tropane alkaloids, and that
ingestion of AT can lead to anticholinergic poisoning. CASE PRESENTATION: A 64
year-old Korean female presented with acute mental changes caused by inadvertent
ingestion of the petals of AT flowers used as a garnish in a traditional Korean
food (bibimbop). She regained her usual level of awareness after 10 hours.
CONCLUSION: Considering its easy availability, the toxicity of AT should be
addressed to prevent accidental and intentional poisoning by this ornamental
plant.
PMID- 25138631
TI - Partial gravity unloading inhibits bone healing responses in a large animal
model.
AB - The reduction in mechanical loading associated with space travel results in
dramatic decreases in the bone mineral density (BMD) and mechanical strength of
skeletal tissue resulting in increased fracture risk during spaceflight missions.
Previous rodent studies have highlighted distinct bone healing differences in
animals in gravitational environments versus those during spaceflight. While
these data have demonstrated that microgravity has deleterious effects on
fracture healing, the direct translation of these results to human skeletal
repair remains problematic due to substantial differences between rodent and
human bone. Thus, the objective of this study was to investigate the effects of
partial gravitational unloading on long-bone fracture healing in a previously
developed large animal Haversian bone model. In vivo measurements demonstrated
significantly higher orthopedic plate strains (i.e. load burden) in the Partial
Unloading (PU) Group as compared to the Full Loading (FL) Group following the 28
day healing period due to inhibited healing in the reduced loading environment.
DEXA BMD in the metatarsus of the PU Group decreased 17.6% (p<0.01) at the time
of the ostectomy surgery. Four-point bending stiffness of the PU Group was 4.4
times lower than that of the FL Group (p<0.01), while uCT and histomorphometry
demonstrated reduced periosteal callus area (p<0.05), mineralizing surface
(p<0.05), mineral apposition rate (p<0.001), bone formation rate (p<0.001), and
periosteal/endosteal osteoblast numbers (p<0.001/p<0.01, respectively) as well as
increased periosteal osteoclast number (p<0.05). These data provide strong
evidence that the mechanical environment dramatically affects the fracture
healing cascade, and likely has a negative impact on Haversian system healing
during spaceflight.
PMID- 25138633
TI - Initial influence of right versus left lateral recumbency on the radiographic
finding of duodenal gas on subsequent survey ventrodorsal projections of the
canine abdomen.
AB - Identification of the duodenum and potential abnormalities on survey abdominal
radiographs is often difficult unless it contains gas. This study investigated
the effect of patient positioning on the presence of duodenal gas in survey
abdominal radiographs. One hundred dogs receiving a three-view survey abdominal
radiographic study were enrolled in a prospective, randomized study where all
dogs were divided into two groups. Group A (n = 51) dogs had a left lateral
projection first, followed by a ventrodorsal projection, ending with a right
lateral projection. Group B (n = 49) dogs had a right lateral projection first,
followed by a ventrodorsal projection, ending with a left lateral projection. The
presence of gas within the duodenum and level of distribution of gas throughout
the duodenum were recorded for all three projections. In addition, the presence
or absence of duodenal pseudoulcers was evaluated on all three projections for
each dog. The results for the two groups were compared using Chi-square analysis
with a P-value of less than 0.05 being considered significant. Results showed
that dogs first placed in left lateral recumbency were significantly more likely
to have duodenal gas on the subsequent ventrodorsal and right lateral
radiographic projections compared to dogs first placed in right lateral
recumbency (P-value < 0.0001). Pseudoulcers were seen in 11 dogs that had
duodenal gas making the visualization of pseudoulcers on survey abdominal
radiographs somewhat commonplace. This study emphasizes the benefit of using
initial left lateral abdominal projections prior to other views for subsequent
evaluation of the duodenum.
PMID- 25138634
TI - Metabolism of 20-hydroxyvitamin D3 by mouse liver microsomes.
AB - 20-Hydroxyvitamin D3 [20(OH)D3], the major product of CYP11A1 action on vitamin
D3, is biologically active and like 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] can
inhibit proliferation and promote differentiation of a range of cells, and has
anti-inflammatory properties. However, unlike 1,25(OH)2D3, it does not cause
toxic hypercalcemia at high doses and is therefore a good candidate for
therapeutic use to treat hyperproliferative and autoimmune disorders. In this
study we analyzed the ability of mouse liver microsomes to metabolize 20(OH)D3.
The two major products were identified from authentic standards as 20,24
dihydroxyvitamin D3 [20,24(OH)2D3] and 20,25-dihydroxyvitamin D3 [20,25(OH)2D3].
The reactions for synthesis of these two products from 20(OH)D3 displayed similar
Km values suggesting that they were catalyzed by the same cytochrome P450. Some
minor metabolites were produced by reactions with higher Km values for 20(OH)D3.
Some metabolites gave mass spectra suggesting that they were the result of
hydroxylation followed by dehydrogenation. One product had an increase in the
wavelength for maximum absorbance from 263nm seen for 20(OH)D3, to 290nm,
suggesting a new double bond was interacting with the vitamin D-triene
chromophore. The two major products, 20,24(OH)2D3 and 20,25(OH)2D3 have both
previously been shown to have higher potency for inhibition of colony formation
by melanoma cells than 20(OH)D3, thus it appears that metabolism of 20(OH)D3 by
mouse liver microsomes can generate products with enhanced activity.
PMID- 25138635
TI - Corpora lutea of pregnant and pseudopregnant domestic cats reveal similar
steroidogenic capacities during the luteal life span.
AB - In domestic cats, luteal phases of pregnancy and pseudopregnancy (non-pregnant
luteal phase) differ in the course and level of plasma progesterone (P4).
Therefore, we assumed differences in luteal steroidogenic capacities. Here we
present a comprehensive analysis of intraluteal steroid biogenesis in the
domestic cat. We quantitatively measured relative mRNA levels of steroidogenic
acute regulatory protein (STAR), cytochrome P450 oxidases (CYP), hydroxysteroid
dehydrogenases (HSD), steroid reductase (SRD) and enzymes involved in
sulfoconjugation of steroids, i.e. sulfotransferase (SULT) and sulfatase (STS).
Protein expression was analysed by Western Blot for HSD3B. Additionally,
intraluteal steroid contents were determined. During the pseudopregnant luteal
phase, expression of STAR (p=0.005), HSD3B1 (p<0.0001), CYP19A1 (p<0.0001) and
HSD17B7 (p=0.008) decreased from formation of the corpus luteum (CL) onwards.
HSD3B protein expression was highest in the development/maintenance stage of CL
and declined during the subsequent luteal phase of pregnancy and pseudopregnancy.
This was in accordance with decreasing intraluteal levels of P4, oestrogens and
androgens. In contrast, expression of SRD5A1 (p<0.001) increased with progression
through stages of the pseudopregnant CL, being indicative of P4 metabolism via an
alternate pathway to dihydrotestosterone (DHT). Compared to the formation stage,
expression of SULT1E1 was higher in all other luteal stages of pseudopregnancy
(p=0.004), implying a potential sulfoconjugation of oestrogens. Expression of
CYP11A1 and CYP17A1 was unaffected by the luteal stage (p>0.05), suggesting a
permanent capacity of cat CL to convert progestogens via androgen and oestrogen
pathways. In general, mRNA expression profiles of steroidogenic enzymes during
the pregnant luteal phase reflected the pseudopregnancy profiles. Intraluteal
oestrogen (p<0.0001) and androgen (p=0.008) levels were higher in the formation
stage compared to the following luteal stages of pseudopregnancy. Concentrations
of P4 were higher in the development/maintenance compared to the regression
stages (p=0.01). We conclude that cat CL of the same histomorphological stage are
characterised by identical steroidogenic capacities independently of an on-going
pregnancy.
PMID- 25138636
TI - Zinc oxide nanoparticles induced oxidative stress in mouse bone marrow
mesenchymal stem cells.
AB - Engineered nanoparticles are developed for various applications in industrial,
electrical, agricultural, pharmaceutical and medical fields due to their unique
properties. Nanoparticles such as TiO(2) and ZnO are widely used in cosmetics for
UV protection. The toxicological investigations of ZnO NPs are highly recommended
because of the increasing use in various industrial and consumer products. The
toxic potential of ZnO NPs was assumed to be caused by the release of free Zn+
ions in the medium. Many of the in vivo studies suggest the toxic nature of ZnO
NPs, the in vitro studies are certainly important to elucidate the mechanism of
toxicity. This study examined the toxicity of ZnO NPs with the average size of 6
8 nm on the isolated mice bone marrow mesenchymal stem cells. The study focuses
on the cytotoxicity and oxidative stress-mediated cellular responses upon
exposure to ZnO NPs. The results indicated that the exposure to ZnO NPs
significantly affects cellular viability in a dose-dependent manner. Formation of
reactive oxygen species (ROS) was found to be the mechanism of cellular toxicity.
The release of Zn(+) ions from the nanoparticles, due to the instability of ZnO
NPs in the acidic compartment of lysosomes, also increases the ROS generation. In
addition to increased ROS production, damage of lysosomal membrane and the
activation of executioner caspase-3 and caspase-7 were observed, which eventually
ends in apoptosis.
PMID- 25138638
TI - Preparation of dibenzo[e,g]isoindol-1-ones via Scholl-type oxidative cyclization
reactions.
AB - A flexible synthesis of dibenzo[e,g]isoindol-1-ones has been developed.
Dibenzo[e,g]isoindol-1-ones represent simplified benzenoid analogues of
biological indolo[2,3-a]pyrrolo[3,4-c]carbazol-5-ones (indolocarbazoles),
compounds that have demonstrated a wide range of biological activity. The
synthesis of the title compounds involved tetramic acid sulfonates. Different
aryl groups were introduced at C4 of the heterocyclic ring via Suzuki-Miyaura
cross-coupling reactions. Finally, mild Scholl-type oxidative cyclizations
mediated by phenyliodine(III) bis(trifluoroacetate) (PIFA) converted some of the
latter compounds into the corresponding dibenzo[e,g]isoindol-1-ones. A systematic
study of the oxidative cyclization revealed the following reactivity trend: 3,4
dimethoxyphenyl ? 3-methoxyphenyl > 3,4,5-trimethoxyphenyl > 4-methoxyphenyl ~
phenyl. Overall, the oxidative cyclization required at least two methoxy groups
distributed in the aromatic rings, at least one of which had to be located para
to the site of the cyclization.
PMID- 25138637
TI - G-protein-coupled receptor cell signaling pathways mediating embryonic chick
retinal growth cone collapse induced by lysophosphatidic acid and sphingosine-1
phosphate.
AB - In the development of the nervous system, one of the critical aspects is the
proper navigation of axons to their targets, i.e. the problem of axonal guidance.
We used the chick visual system as a model to investigate the role of the
lysophospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P)
as potential axon guidance cues. We showed that both LPA and S1P cause a
specific, dose-dependent growth cone collapse of retinal neurons in vitro in the
chick model system, with slight differences compared to the mouse but very
similar to observations in Xenopus. Because LPA and S1P receptors are G-protein
coupled receptors, we analyzed the intracellular signaling pathways using
pharmacological inhibitors in chick retinal neurons. Blocking rho kinase (ROCK)
prevented growth cone collapse by LPA and S1P, while blocking PLC or chelating
calcium had no effect on growth cone collapse. Inhibition of Gi/o with pertussis
toxin resulted in a partial reduction of growth cone collapse, both with LPA and
with S1P. Inhibition of p38 blocked growth cone collapse mediated by LPA but not
S1P. Thus, in addition to the involvement of the G12/13-ROCK pathway, LPA- and
S1P-induced collapse of chick retinal growth cones has a partial requirement for
Gi/o.
PMID- 25138640
TI - Microorganism-induced suppression of allergic airway disease: novel therapies on
the horizon?
AB - Allergic airway disease is a major global health burden, and novel treatment
options are urgently needed. Numerous epidemiological and experimental studies
suggest that certain helminths and bacteria protect against respiratory
allergies. These microorganisms are strong regulators of the immune system, and
various potential regulatory mechanisms by which they protect against allergic
airway inflammation have been proposed. Whereas early studies addressed the
beneficial effect of natural infections, the focus now shifts toward identifying
the dominant protective molecules and exploring their efficacy in models of
allergic airway disease. In this article, we will review the evidence for microbe
mediated protection from allergic airway disease, the potential modes of action
involved and discuss advances as well as limitations in the translation of this
knowledge into novel treatment strategies against allergic airway disease.
PMID- 25138639
TI - The retrovirus/superantigen hypothesis of multiple sclerosis.
AB - The pathogenesis of multiple sclerosis (MS) is as yet unknown. Commonly, MS is
assumed to be due to an autoimmune inflammation of the central nervous system
(CNS). Neurodegeneration is regarded to be a secondary reaction. This concept is
increasingly being challenged. Human endogenous retroviruses (HERV) that could be
locally activated in the CNS have been proposed as an alternative concept. HERV
encoded envelope proteins (env) can act as strong immune stimulators
(superantigens). Thus, slow disease progression following neurodegeneration might
be induced by re-activation of HERV expression directly, while relapses in
parallel to inflammation might be secondary to the expression of HERV-encoded
superantigens. It has been shown previously that T-cell superantigens are capable
to induce a cellular inflammatory reaction in the CNS of experimental animals
similar to that in MS. Furthermore, B-cell superantigens have been shown to
activate blood leucocytes in vitro to produce immunoglobulin in an oligoclonal
manner. It remains to be established, whether the outlined hypothesis accords
with all known features of MS. Furthermore, anti-HERV agents may be taken into
consideration to enrich and improve MS therapy.
PMID- 25138641
TI - A comparison of conventional methods for the quantification of bacterial cells
after exposure to metal oxide nanoparticles.
AB - BACKGROUND: Due to potential interference of nanoparticles on bacterial
quantification, there is a challenge to develop a fast, accurate and reproducible
method for bacterial quantification. Currently various bacterial quantification
methods are used by researchers performing nanoparticles study, but there has
been no efficacy evaluation of these methods. Here we study interference of
nanoparticles on three most commonly used conventional bacterial quantification
methods, including colony counting to determine the colony-forming units (CFU),
spectrophotometer method of optical density (OD) measurement, and flow cytometry
(FCM). RESULTS: Three oxide nanoparticles including ZnO, TiO2, and SiO2 and four
bacterial species including Salmonella enterica serovar Newport, Staphylococcus
epidermidis, Enterococcus faecalis, and Escherichia coli were included in the
test. Results showed that there is no apparent interference of the oxide
nanoparticles on quantifications of all four bacterial species by FCM
measurement; CFU counting is time consuming, less accurate and not suitable for
automation; and the spectrophotometer method using OD measurement was the most
unreliable method to quantify and detect the bacteria in the presence of the
nanoparticles. CONCLUSION: In summary, FCM measurement proved to be the best
method, which is suitable for rapid, accurate and automatic detection of bacteria
in the presence of the nanoparticles.
PMID- 25138642
TI - Moderate alcohol exposure during early brain development increases stimulus
response habits in adulthood.
AB - Exposure to alcohol during early central nervous system development has been
shown variously to affect aspects of physiological and behavioural development.
In extreme cases, this can extend to craniofacial defects, severe developmental
delay and mental retardation. At more moderate levels, subtle differences in
brain morphology and behaviour have been observed. One clear effect of
developmental alcohol exposure is an increase in the propensity to develop
alcoholism and other addictions. The mechanisms by which this occurs, however,
are not currently understood. In this study, we tested the hypothesis that adult
zebrafish chronically exposed to moderate levels of ethanol during early brain
ontogenesis would show an increase in conditioned place preference for alcohol
and an increased propensity towards habit formation, a key component of drug
addiction in humans. We found support for both of these hypotheses and found that
the exposed fish had changes in mRNA expression patterns for dopamine receptor,
nicotinic acetylcholine receptor and MU-opioid receptor encoding genes.
Collectively, these data show an explicit link between the increased proclivity
for addiction and addiction-related behaviour following exposure to ethanol
during early brain development and alterations in the neural circuits underlying
habit learning.
PMID- 25138643
TI - Spatiotemporally consistent genomic signatures of reproductive isolation in a
moving hybrid zone.
AB - Studies of hybrid zone dynamics often investigate a single sampling period and
draw conclusions from that temporal snapshot. Stochasticity can, however, result
in loci with spurious outlier patterns, which is exacerbated by limited temporal
or geographic sampling. Comparing admixed populations from different geographic
regions is one way to detect repeatedly divergent genomic regions potentially
involved in reproductive isolation. Temporal comparisons also allow us to control
partially for the role of stochasticity, but the power of temporal sampling has
not yet been adequately explored. In North America, black-capped (Poecile
atricapillus) and Carolina (P. carolinensis) chickadees hybridize in a contact
zone extending from New Jersey to Kansas. The hybrid zone is likely maintained by
strong intrinsic selection against hybrids, and it is moving north. We used a
reduced representation genomic approach and temporally spaced sampling-two
samples of ~80 individuals separated by a decade-to determine the pattern and
consistency of selection and genomic introgression in the chickadee hybrid zone.
We report consistently low introgression for highly divergent loci between P.
atricapillus and P. carolinensis in this moving hybrid zone. This is strong
evidence that these loci may be linked to genomic regions involved in
reproductive isolation between chickadees.
PMID- 25138644
TI - SCAI expert consensus statement for renal artery stenting appropriate use.
AB - The pathophysiology of atherosclerotic renal artery stenosis (RAS) includes
activation of the renin-angiotensin-aldosterone axis with resultant renovascular
hypertension. Renal artery stenting has emerged as the primary revascularization
strategy in most patients with hemodynamically significant atherosclerotic RAS.
Despite the frequency with which hemodynamically significant RAS is observed and
high rates of technical success of renal artery stenting, there remains
considerable debate among experts regarding the role of medical therapy versus
revascularization for renovascular hypertension. Modern, prospective, multicenter
registries continue to demonstrate improvement in systolic and diastolic blood
pressure with excellent safety profiles in patients with RAS. Modern randomized,
controlled clinical trials of optimal medical therapy versus renal stenting
particularly designed to demonstrate preservation in renal function after renal
artery stenting have demonstrated limited benefit. However, these trials
frequently excluded patients that may benefit from renal artery stenting. This
document was developed to guide physicians in the modern practical application of
renal stenting, to highlight the current limitations in the peer-reviewed
literature, to suggest best-practices in the performance of renal stenting and to
identify opportunities to advance the field.
PMID- 25138645
TI - Differences between motor point and innervation zone locations in the biceps
brachii. An exploratory consideration for the treatment of spasticity with
botulinum toxin.
AB - BACKGROUND: Botulinum toxin (BTX) acts on the neuromuscular junction which can be
located by the innervation zone (IZ). Clinically, the motor point (MP) is
homologous to the IZ and it is used as the injection site of BTX. Differences in
the effectiveness of the application of BTX between MP and IZ locations have been
determined. OBJECTIVE: Compare the location of the MP obtained using electrical
stimulation and the location of the IZ using a linear surface electrodes array on
the biceps brachii muscle. METHODS: The biceps brachii muscle of twenty men was
assessed. The MP was located using the torque measurement generated by electrical
stimulation. The IZ was detected using a linear surface electrodes array.
RESULTS: A difference between the MP and the IZ positions (75.8 vs. 86.5mm, delta
10.7 mm; p=0.003, post-hoc power 0.89) was observed. DISCUSSION: The magnitude of
the difference between the MP and the IZ may be clinically relevant. The IZ
location using surface electromyography as a guide to optimize BTX injection is
proposed.
PMID- 25138646
TI - Rigid and Elastic taping changes scapular kinematics and pain in subjects with
shoulder impingement syndrome; an experimental study.
AB - Rigid and Elastic scapular taping is used in physical rehabilitation of shoulder
impingement syndrome (SIS). It is believed to reduce pain and normalise scapular
movement patterns. However, there is insufficient evidence to support its use.
The aim of the study was to investigate the effect of Rigid and Elastic taping
techniques on the scapular kinematics and pain in patients with SIS. Eleven
patients with SIS participated in the study. They performed elevation and
lowering of the arm in the scapular and sagittal planes under three conditions:
Baseline, Rigid taping and Elastic taping. The movements of the thorax, humerus
and scapula were tracked. Scapular displacements and scapulothoracic joint
rotations were calculated. Subjects used a visual analogue scale to rate the
intensity of pain at rest and during movements in both planes. Both taping
techniques externally rotated the scapula in sagittal plane movements (p<0.05)
and resulted in reduced pain. In the scapular plane, Elastic taping increased the
scapular retraction (p<0.05) and posterior displacement (p<0.01), but neither of
the taping techniques had an effect on pain in this plane. In conclusion, both
taping techniques had an effect on scapular kinematics and pain in movements
occurring in the sagittal plane. Elastic taping also affected scapular kinematics
in scapular plane movements, but without the concomitant decrease in pain.
PMID- 25138648
TI - Factors Related to the Differential Preference for Cardiopulmonary Resuscitation
Between Patients With Terminal Cancer and That of Their Respective Family
Caregivers.
AB - There is little information regarding concordance between preferences for end-of
life care of terminally ill patients with cancer and those of their family
caregivers. A cross-sectional exploration of cardiopulmonary resuscitation (CPR)
preference in 361 dyads was conducted. Patients or family caregivers who were
willing to approve CPR were compared with dyads who did not support CPR. The
patient's quality of life was more associated with family caregiver's willingness
than patient's willingness. A patient was more likely to prefer CPR than their
caregiver in dyads of females and emotionally stable patients. A family caregiver
showed stronger support for CPR if the patient had controlled pain or stable
health and the family caregiver had not been counseled for CPR. Communications
should be focused on these individuals to improve the planning of end-of-life
care.
PMID- 25138647
TI - Functional connectivity in frontal-striatal brain networks and cocaine self
administration in female rhesus monkeys.
AB - RATIONALE: Cocaine addiction is characterized by alternating cycles of abstinence
and relapse and loss of control of drug use despite severe negative life
consequences associated with its abuse. OBJECTIVE: The objective of the present
study was to elucidate critical neural circuits involved in individual
vulnerabilities to resumption of cocaine self-administration following prolonged
abstinence. METHODS: The subjects were three female rhesus monkeys in prolonged
abstinence following a long history of cocaine self-administration. Initial
experiments examined the effects of acute cocaine administration (0.3 mg/kg, IV)
on functional brain connectivity across the whole brain and in specific brain
networks related to behavioral control using functional magnetic resonance
imaging in fully conscious subjects. Subsequently, these subjects were allowed to
resume cocaine self-administration to determine whether loss of basal
connectivity within specific brain networks predicted the magnitude of resumption
of cocaine intake following prolonged abstinence. RESULTS: Acute cocaine
administration robustly decreased global functional connectivity and selectively
impaired top-down prefrontal circuits that control behavior, while sparing
connectivity of striatal areas within limbic circuits. Importantly, impaired
connectivity between prefrontal and striatal areas during abstinence predicted
cocaine intake when these subjects were provided renewed access to cocaine.
CONCLUSIONS: Based on these findings, loss of prefrontal to striatal functional
connectivity may be a critical mechanism underlying the negative downward spiral
of cycles of abstinence and relapse that characterizes cocaine addiction.
PMID- 25138649
TI - Knowledge About Hospice: Exploring Misconceptions, Attitudes, and Preferences for
Care.
AB - CONTEXT: Poor knowledge and misperceptions about hospice are believed to be
common, but there is scant evidence about the public's understanding of hospice.
OBJECTIVES: To examine hospice knowledge among geographically diverse adults; and
describe linkages between knowledge, attitudes and beliefs about hospice care,
and demographics. METHODS: A small cross-sectional telephone survey of adults
living in the contiguous US was conducted using randomly selected numbers (cell
phone and landline) and over-sampling of minorities. Measures assessed knowledge
(23-item test), attitudes (8-item scale), experiences and preferences related to
hospice. RESULTS: 123 participants completed surveys (response rate 46%). 106
(86%) had heard about hospice, 65 (54%) of whom had a personal experience with
hospice. Participants had an average hospice knowledge test score of 18 (SD =
3.4) indicating moderate knowledge of hospice. A majority of respondents (62%)
did not know that hospice cannot provide concurrent cure-oriented care.
Misperceptions about eligibility, coverage of hospice, the provision of hospice
in nursing homes or to persons who live alone were not uncommon (missed by >20%).
Greater knowledge of hospice was associated with more favorable attitudes about
the hospice philosophy of care (r = .22, p = .023) and a greater preference for
hospice (p = .049). Respondents who were more educated, worked in the medical
field, were non-Hispanic White, and had direct experience with hospice were also
more likely to be more knowledgeable about hospice. CONCLUSION: Despite
relatively high hospice awareness and favorability, myths and misperceptions
about hospice still abound--and may drive ethnic disparities in end-of-life care.
Educational interventions and future study are needed.
PMID- 25138651
TI - Effect of diet- and lifestyle-based metabolic risk-modifying interventions on
preeclampsia: a meta-analysis.
AB - OBJECTIVE: To evaluate the effect of dietary and lifestyle interventions with the
potential to modify metabolic risk factors on the risk of preeclampsia. DATA
SOURCES: We searched MEDLINE, EMBASE and Cochrane from inception until February
2013. Randomized trials in pregnant women evaluating the effect of dietary and
lifestyle interventions with the potential to modify metabolic risks such as
obesity, hyperlipidemia, hyperglycemia and hypertension on the risk of
preeclampsia were included. STUDY SELECTION: Two independent reviewers selected
studies, extracted data and assessed quality. Results were summarized as pooled
relative risks (RR) for dichotomous data. RESULTS: Eighteen studies (8712 women)
met our search criteria for inclusion. Six studies evaluated diet (2695 women),
six studied mixed interventions with diet, physical activity and lifestyle (1438
women) and six assessed essential fatty acid supplementation (4579 women). The
interventions overall reduced the risk of preeclampsia (RR 0.81, 95% CI 0.69
0.94; p = 0.006 I(2) = 0%) compared with the control group. Dietary interventions
reduced the risk of preeclampsia by 33% (RR 0.67, 95% CI 0.53-0.85; p = 0.001;
I(2) = 0%). There was no reduction in the risk of preeclampsia with mixed
interventions (RR 0.93, 95% CI 0.66-1.32, p = 0.68, I(2) = 0%) or fatty acid
supplementation (RR 0.92, 95% CI 0.71-1.18; p = 0.49, I(2) = 15%). Meta
regression showed a borderline impact of gestational diabetes status (p = 0.05)
on the observed effect. CONCLUSION: Dietary and lifestyle interventions have the
potential to reduce the risk of preeclampsia. The effect of additional
therapeutic interventions in women with gestational diabetes mellitus on
preeclampsia is not known.
PMID- 25138650
TI - Circadian variation of mineral and bone parameters in end-stage renal disease.
AB - BACKGROUND: Mineral and bone parameters are actively managed in end-stage renal
disease (ESRD). However, whether these undergo circadian variation is not known.
We investigated the circadian variation of mineral and bone parameters in
patients on long-term hemodialysis. METHODS: Seventeen ESRD patients on long-term
hemodialysis and eight volunteers without kidney disease were enrolled. Subjects
had all medications that affect calcium-phosphate-parathyroid hormone balance
(phosphate binders, vitamin D analogues, and calcimimetics) discontinued.
Thereafter, for a period of 5 days, subjects consumed a diet controlled in
calcium (1,200 mg per day) and phosphorus (1,000 mg per day) content. On the
sixth day (a non-dialysis day for the ESRD patients), enrollees underwent twelve
2-h blood draws for phosphate, ionized calcium, parathyroid hormone (PTH), total
25-hydroxy vitamin D (25OHD), and fibroblast growth factor-23 (FGF-23). RESULTS:
In the ESRD patients plasma phosphate demonstrated significant circadian
variation (P < 0.00001). The peak occurred around 3:30 am and nadir occurred
around 11:00 am. Ionized calcium (P = 0.0036), PTH (P = 0.0004) and 25OHD (P =
0.009) also varied significantly during the circadian period; for ionized calcium
peak and nadir occurred around 12:15 pm and 8:00 pm, parathyroid hormone 5:45 pm
and 10:15 am, and 25OHD 9:45 am and 4:00 pm respectively. FGF-23 did not show a
significant circadian variation. Only phosphate (P < 0.0001) and PTH (P =
0.00008) demonstrated circadian variation in the control group. CONCLUSIONS:
Blood concentrations of phosphate, calcium, PTH and 25-hydroxy vitamin D, exhibit
a circadian variation in patients with ESRD. Knowledge of these phenomena is
pertinent for the interpretation of clinical testing.
PMID- 25138652
TI - CoroEval: a multi-platform, multi-modality tool for the evaluation of 3D coronary
vessel reconstructions.
AB - We present a software, called CoroEval, for the evaluation of 3D coronary vessel
reconstructions from clinical data. It runs on multiple operating systems and is
designed to be independent of the imaging modality used. At this point, its
purpose is the comparison of reconstruction algorithms or acquisition protocols,
not the clinical diagnosis. Implemented metrics are vessel sharpness and
diameter. All measurements are taken from the raw intensity data to be
independent of display windowing functions. The user can either import a vessel
centreline segmentation from other software, or perform a manual segmentation in
CoroEval. An automated segmentation correction algorithm is provided to improve
non-perfect centrelines. With default settings, measurements are taken at 1 mm
intervals along the vessel centreline and from 10 different angles at each
measurement point. This allows for outlier detection and noise-robust
measurements without the burden and subjectivity a manual measurement process
would incur. Graphical measurement results can be directly exported to vector or
bitmap graphics for integration into scientific publications. Centreline and
lumen segmentations can be exported as point clouds and in various mesh formats.
We evaluated the diameter measurement process using three phantom datasets. An
average deviation of 0.03 +/- 0.03 mm was found. The software is available in
binary and source code form at http://www5.cs.fau.de/CoroEval/.
PMID- 25138653
TI - Time to gain trust and change--experiences of attachment and mindfulness-based
cognitive therapy among patients with chronic pain and psychiatric co-morbidity.
AB - The treatment of patients with chronic pain disorders is complex. In the
rehabilitation of these patients, coping with chronic pain is seen as important.
The aim of this study was to explore the meaning of attachment and mindfulness
based cognitive therapy (CT) among patients with chronic pain and psychiatric co
morbidity. A phenomenological approach within a lifeworld perspective was used.
In total, 10 patients were interviewed after completion of 7- to 13-month
therapy. The findings reveal that the therapy and the process of interaction with
the therapist were meaningful for the patients' well-being and for a better
management of pain. During the therapy, the patients were able to initiate a
movement of change. Thus, CT with focus on attachment and mindfulness seems to be
of value for these patients. The therapy used in this study was adjusted to the
patients' special needs, and a trained psychotherapist with a special knowledge
of patients with chronic pain might be required.
PMID- 25138654
TI - Stiff muscle fibers in calf muscles of patients with cerebral palsy lead to high
passive muscle stiffness.
AB - Cerebral palsy (CP), caused by an injury to the developing brain, can lead to
alterations in muscle function. Subsequently, increased muscle stiffness and
decreased joint range of motion are often seen in patients with CP. We examined
mechanical and biochemical properties of the gastrocnemius and soleus muscles,
which are involved in equinus muscle contracture. Passive mechanical testing of
single muscle fibers from gastrocnemius and soleus muscle of patients with CP
undergoing surgery for equinus deformity showed a significant increase in fiber
stiffness (p<0.01). Bundles of fibers that included their surrounding connective
tissues showed no stiffness difference (p=0.28).). When in vivo sarcomere lengths
were measured and fiber and bundle stiffness compared at these lengths, both
fibers and bundles of patients with CP were predicted to be much stiffer in vivo
compared to typically developing (TD) individuals. Interestingly, differences in
fiber and bundle stiffness were not explained by typical biochemical measures
such as titin molecular weight (a giant protein thought to impact fiber
stiffness) or collagen content (a proxy for extracellular matrix amount). We
suggest that the passive mechanical properties of fibers and bundles are thus
poorly understood.
PMID- 25138655
TI - Controls on foliar nutrient and aluminium concentrations in a tropical tree
flora: phylogeny, soil chemistry and interactions among elements.
AB - Foliar elemental concentrations are predictors of life-history variation and
contribute to spatial patterns in biogeochemical cycling. We examined the
contributions of habitat association, local soil environment, and elemental
interactions to variation in foliar elemental concentrations in tropical trees
using methods that account for phylogeny. We sampled top-soils and leaves of 58
tropical trees in heath forest (HF) on nutrient-poor sand and mixed dipterocarp
forest (MDF) on nutrient-rich clay soils. A phylogenetic generalized least
squares method was used to determine how foliar nutrient and aluminium (Al)
concentrations varied in response to habitat distribution, soil chemistry and
other elemental concentrations. Foliar nitrogen (N) and Al concentrations were
greater for specialists of MDF than for specialists of HF, while foliar calcium
(Ca) concentrations showed the opposite trend. Foliar magnesium (Mg)
concentrations were lower for generalists than for MDF specialists. Foliar
element concentrations were correlated with fine-scale variation in soil
chemistry in phylogenetically controlled analyses across species, but there was
limited within-species plasticity in foliar elemental concentrations. Among Al
accumulators, foliar Al concentration was positively associated with foliar Ca
and Mg concentrations, and negatively associated with foliar phosphorus (P)
concentrations. The Al-accumulation trait and relationships between foliar
elemental and Al concentrations may contribute to species habitat partitioning
and ecosystem-level differences in biogeochemical cycles.
PMID- 25138657
TI - Stoichiometrically controlled revocable self-assembled "spiro" versus quadruple
stranded "double-decker" type coordination cages.
AB - The simple combination of Pd(II) with the tris-monodentate ligand bis(pyridin-3
ylmethyl) pyridine-3,5-dicarboxylate, L, at ratios of 1:2 and 3:4 demonstrated
the stoichiometrically controlled exclusive formation of the "spiro-type" Pd1L2
macrocycle, 1, and the quadruple-stranded Pd3L4 cage, 2, respectively. The
architecture of 2 is elaborated with two compartments that can accommodate two
units of fluoride, chloride, or bromide ions, one in each of the enclosures.
However, the entry of iodide is altogether restricted. Complexes 1 and 2 are
interconvertible under suitable conditions.
PMID- 25138656
TI - Iron oxide encapsulated by ruthenium hydroxyapatite as heterogeneous catalyst for
the synthesis of 2,5-diformylfuran.
AB - Magnetic gamma-Fe2 O3 nanocrystallites encapsulated by hydroxyapatite (HAP),
HAP@gamma-Fe2 O3 , were prepared followed by cation exchange of Ca(2+) on the
external HAP surface with Ru(3+) to give the gamma-Fe2 O3 @HAP-Ru catalyst. The
structure of the as-prepared catalyst was characterized, and its catalytic
activity was studied in the aerobic oxidation of 5-hydroxymethylfurfural (HMF).
gamma-Fe2 O3 @HAP-Ru showed a high catalytic activity for the aerobic oxidation
of HMF into 2,5-diformylfuran (DFF). A high DFF yield of 89.1 % with an HMF
conversion of 100% was obtained after 4 h at 90 degrees C. Importantly, the
synthesis of DFF from fructose was realized by two consecutive steps. The
dehydration of fructose in the presence of a magnetic acid catalyst (Fe3 O4 @SiO2
SO3 H) produced HMF in a yield of 90.1%. Then the Fe3 O4 @SiO2 ?SO3 H catalyst
was removed from the reaction solution with a permanent magnet, and HMF in the
resulting solution was further oxidized to DFF with a yield of 79.1% based on
fructose. The synthesis of DFF from fructose by two steps avoids the tedious
separation of the intermediate HMF, which saves time and energy.
PMID- 25138658
TI - [Visual experiences during cataract surgery under topical anesthesia].
AB - BACKGROUND: Cataract patients observe structures, colors and movements during
surgery. Is there any pattern to their visual experiences? METHODS: From 2005 to
2011 a total of 20,000 phacoemulsification procedures were performed using
topical anesthesia. From these patients we received 45 pictures which had been
painted to reflect intraoperative their visual impressions so that approximately
1 out of 500 of the patients painted a picture. A further 98 patients were
questioned postoperatively about their intraoperative visual impressions and were
shown the 45 pictures. They described their own visual experiences and any
similarities with the 45 pictures were documented. RESULTS: All patients were
awake and cooperative during surgery. Afterwards they described their visual
experiences whereby 36 patients saw mainly blue, 32 red/pink and 27 saw yellow
colors. Out of the 45 pictures 30 (67%) were identified as being similar to their
own visual images and 10 patients could not describe any postoperative visual
phenomena. CONCLUSION: Patients notice optical phenomena during cataract surgery
under topical anesthesia with eye drops. Visual images are often similar among
patients. The surgeon can use this knowledge to explain these experiences while
talking to the patient intraoperatively. This may reassure patients during
surgery.
PMID- 25138659
TI - Resource utilization pattern and cost of tuberculosis treatment from the provider
and patient perspectives in the state of Penang, Malaysia.
AB - BACKGROUND: Studies from both developed and developing countries have
demonstrated a considerable fluctuation in the average cost of TB treatment. The
objective of this study was to analyze the medical resource utilization among new
smear positive pulmonary tuberculosis patients. We also estimated the cost of
tuberculosis treatment from the provider and patient perspectives, and identified
the significant cost driving factors. METHODS: All new smear positive pulmonary
tuberculosis patients who were registered at the chest clinic of the Penang
General Hospital, between March 2010 and February 2011, were invited to
participate in the study. Provider sector costs were estimated using bottom-up,
micro-costing technique. For the calculation of costs from the patients'
perspective, all eligible patients who agreed to participate in the study were
interviewed after the intensive phase and subsequently at the end of the
treatment by a trained nurse. PASW was used to analyze the data (Predictive
Analysis SoftWare, version 19.0, Armonk, NY: IBM Corp.). RESULTS: During the
study period, 226 patients completed the treatment. However, complete costing
data were available for 212 patients. The most highly utilized resources were
chest X-ray followed by sputum smear examination. Only a smaller proportion of
the patients were hospitalized. The average provider sector cost was MYR 992.34
(i.e., USD 325.35 per patient) whereby the average patient sector cost was MYR
1225.80 (i.e., USD 401.90 per patient). The average patient sector cost of our
study population accounted for 5.7% of their annual family income. In multiple
linear regression analysis, prolonged treatment duration (i.e., > 6 months) was
the only predictor of higher provider sector costs whereby higher patient sector
costs were determined by greater household income and persistent cough at the end
of the intensive phase of the treatment. CONCLUSION: In relation to average
provider sector cost, our estimates are substantially higher than the budget
allocated by the Ministry of Health for the treatment of a tuberculosis case in
Malaysia. The expenses borne by the patients and their families on the treatment
of the current episode of tuberculosis were not catastrophic for them.
PMID- 25138660
TI - Association of congenital left renal vein anomalies and unexplained hematuria:
multidetector computed tomography findings.
AB - OBJECTIVES: To investigate whether congenital renal vein anomalies are involved
in the etiology of hematuria by analyzing abdominal multidetector computed
tomography (MDCT) results. METHODS: Six hundred and eighty patients undergoing
MDCT for various abdominal pathologies in whom possible causes of hematuria were
excluded were retrospectively assessed in terms of left renal vein anomalies,
such as circumaortic left renal vein (CLRV), retroaortic left renal vein (RLRV)
and multiple renal vein (MRV). Patients with CLRV, RLRV or MRV and patients with
normal left renal veins were compared in terms of the presence of hematuria.
RESULTS: Left renal vein anomalies were detected in 100 patients (14.7%). RLRV,
CLRV and MRV were identified in 5.4, 2.5 and 6.8% of patients, respectively.
Hematuria was determined in 8.1% of patients with an RLRV anomaly and in 10.5% of
patients with no RLRV anomaly (p=0.633). Hematuria was detected in 23.5% of
patients with a CLRV anomaly and 10.1% of those without (p=0.074), and in 21.7%
of patients with an MRV anomaly and 9.6% of those without (p=0.009). CONCLUSIONS:
In addition to increasing risk of complication during retroperitoneal surgery,
numeric congenital renal vein anomalies are also significant in terms of leading
to clinical symptoms such as hematuria.
PMID- 25138661
TI - Satiety effects of a whole-grain fibre composite ingredient: reduced food intake
and appetite ratings.
AB - The current study assesses the impact on appetite and food intake of a novel co
processed ingredient containing a viscous fibre and whole-grain high-amylose corn
flour, a source of type 1 and type 2 resistant starch (HAM-RS). Ninety adults
completed a crossover, placebo-controlled study comparing two doses of the
ingredient (20 and 30 g) to a maltodextrin control in a fruit-based smoothie
served with breakfast. Ad libitum food intake was measured over the day and
visual analogue scales were used to assess subjective appetite sensations.
Subjects consumed 7% less energy intake at dinner following the 30 g dose (p =
0.02) compared to control. In addition, a trend for lower lunch intake (5% less
weight of food) was observed for the 20 g dose (p = 0.10). Reductions were also
observed for the two meals combined, with 3% lower energy intake for the 20 g
dose (p = 0.04) and 5% less weight of food consumed for the 30 g dose (p = 0.04).
Lower ratings of hunger were reported at 3 h after breakfast for both doses and
also at 2 and 3 h after lunch for the 30 g dose. With ratings combined to compute
an overall appetite score, a trend for lower appetite scores at 3 h after
breakfast was found for both doses. Consistent with this, significant reductions
in AUC hunger and prospective consumption were identified in the 30 g condition.
A similar pattern of results was observed for fullness and desire to eat. The
results of this study show that a new composite satiety ingredient comprised of a
viscous fibre and whole-grain corn flour can affect acute satiety responses in
men and women.
PMID- 25138663
TI - DNA replication timing: Coordinating genome stability with genome regulation on
the X chromosome and beyond.
AB - Recent studies based on next-generation DNA sequencing have revealed that the
female inactive X chromosome is replicated in a rapid, unorganized manner, and
undergoes increased rates of mutation. These observations link the organization
of DNA replication timing to gene regulation on one hand, and to the generation
of mutations on the other hand. More generally, the exceptional biology of the
inactive X chromosome highlights general principles of genome replication. Cells
may control replication timing by a combination of intrinsic replication origin
properties, local chromatin states and global levels of replication factors,
leading to a functional separation between the activity of genes and their
mutation.
PMID- 25138664
TI - The role of jet eccentricity in generating disproportionately elevated
transaortic pressure gradients in patients with aortic stenosis.
AB - In patients with aortic stenosis (AS) and eccentric transaortic flow, greater
pressure loss occurs as the jet collides with the aortic wall together with
delayed and diminished pressure recovery. This leads to the elevated transaortic
valve pressure gradients noted on both Doppler and cardiac catheterization. Such
situations may present a diagnostic dilemma where traditional measures of
stenosis severity indicate severe AS, while imaging modalities of the aortic
valve geometric aortic valve area (GOA) suggest less than severe stenosis. In
this study, we present a series of cases exemplifying this clinical dilemma and
demonstrate how color M-mode, 2D and 3D transthoracic (TTE) and transesophageal
(TEE) echocardiography, cardiac computed tomography angiography (CTA), and
magnetic resonance imaging (MRI), may be used to resolve such discrepancies.
PMID- 25138662
TI - The evolution of mitochondrial genomes in modern frogs (Neobatrachia):
nonadaptive evolution of mitochondrial genome reorganization.
AB - BACKGROUND: Although mitochondrial (mt) gene order is highly conserved among
vertebrates, widespread gene rearrangements occur in anurans, especially in
neobatrachians. Protein coding genes in the mitogenome experience adaptive or
purifying selection, yet the role that selection plays on genomic reorganization
remains unclear. We sequence the mitogenomes of three species of Glandirana and
hot spots of gene rearrangements of 20 frog species to investigate the diversity
of mitogenomic reorganization in the Neobatrachia. By combing these data with
other mitogenomes in GenBank, we evaluate if selective pressures or functional
constraints act on mitogenomic reorganization in the Neobatrachia. We also look
for correlations between tRNA positions and codon usage. RESULTS: Gene
organization in Glandirana was typical of neobatrachian mitogenomes except for
the presence of pseudogene trnS (AGY). Surveyed ranids largely exhibited gene
arrangements typical of neobatrachian mtDNA although some gene rearrangements
occurred. The correlation between codon usage and tRNA positions in
neobatrachians was weak, and did not increase after identifying recurrent
rearrangements as revealed by basal neobatrachians. Codon usage and tRNA
positions were not significantly correlated when considering tRNA gene
duplications or losses. Change in number of tRNA gene copies, which was driven by
genomic reorganization, did not influence codon usage bias. Nucleotide
substitution rates and dN/dS ratios were higher in neobatrachian mitogenomes than
in archaeobatrachians, but the rates of mitogenomic reorganization and mt
nucleotide diversity were not significantly correlated. CONCLUSIONS: No evidence
suggests that adaptive selection drove the reorganization of neobatrachian
mitogenomes. In contrast, protein-coding genes that function in metabolism showed
evidence for purifying selection, and some functional constraints appear to act
on the organization of rRNA and tRNA genes. As important nonadaptive forces,
genetic drift and mutation pressure may drive the fixation and evolution of
mitogenomic reorganizations.
PMID- 25138673
TI - Identification of synergistic Cu/V redox pair in VCu:AlPO-5; a comparison with
VCu:ZSM-5.
AB - Vanadium(V) and copper(II) were co-deposited into AlPO-5 and H-ZSM-5 three
dimensional microporous carriers to yield VCu:AlPO-5 and VCu:ZSM-5. The
materials, along with copper analogues were tested for the selective oxidation of
propene, and the catalysts perform in the following order: VCu:AlPO-5 > Cu:AlPO-5
> VCu:ZSM-5 > Cu:ZSM-5. Acrolein was selectively formed over VCu:AlPO-5 and
Cu:AlPO-5 over a very wide range from 300 to 450 degrees C, whereas VCu:ZSM-5
displays a limited temperature window for acrolein formation (300-350 degrees
C). Hence, the choice of carrier and presence of vanadium as a co-cation greatly
affects the acrolein selectivity and activity window. The vanadium and copper
reduction events were monitored by in situ X-ray Absorption Spectroscopy (XAS)
during C3H6-TPR (1.11%) to 450 degrees C. The Cu(II)/(I) redox pair initiates
reduction of V(V) -> V(IV) in VCu:AlPO-5 and VCu:ZSM-5 at 375 degrees C.
Metallic copper is the major valence fraction above 400 degrees C in both
samples while vanadium is present as V(IV)/V(III) species. In the monometallic
copper analogues Cu(I) is the major valence fraction above 350 degrees C, hence
synergistic effects between the Cu/V pair causes hyper-reduction of copper. EXAFS
shows that copper and vanadium are in close proximity in VCu:AlPO-5 only, being
linked by bridging oxygens (Cu-O-V) believed to interact with propene. By
contrast, propene adsorbs on Bronsted sites in VCu:ZSM-5 inhibiting acrolein
formation at elevated temperatures, as confirmed by DRIFTS. We believe the
reactive Cu/V pair in neutral AlPO-5 generates extralattice oxygens favouring
acrolein formation over a wide temperature range.
PMID- 25138665
TI - An in vitro model of innate lymphoid cell function and differentiation.
AB - Innate lymphoid cells (ILC) are RAG-independent lymphocytes with important roles
in innate immunity, and include group-1 (natural killer (NK) cell, ILC1), group-2
(ILC2), and group-3 (lymphoid tissue inducer (LTi), NCR(+) ILC3) subsets. Group-3
ILC express Rorgammat, produce interleukin (IL)-22, and are critically important
in the normal function of mucosal tissues. Here, we describe a novel model cell
line for the study of ILC function and differentiation. The parental MNK cell
line, derived from NKR-P1B(+) fetal thymocytes, shows a capacity to differentiate
in gammac cytokines. One IL-7-responsive subline, designated MNK-3, expresses
Rorgammat and produces high levels of IL-22 in response to IL-23 and IL-1beta
stimulation. MNK-3 cells display surface markers and transcript expression
characteristic of group-3 ILC, including IL-7Ralpha (CD127), c-kit (CD117), CCR6,
Thy1 (CD90), RANK, RANKL, and lymphotoxin (LTalpha1beta2). Using an in vitro
assay of LTi cell activity, MNK-3 cells induce ICAM-1 and VCAM-1 expression on
stromal cells in a manner dependent upon LTalpha1beta2 expression. A second IL-2
responsive subline, MNK-1, expresses several NK cell receptors, perforin and
granzymes, and shows some cytotoxic activity. Thus, MNK-1 cells serve as a model
of ILC1/NK development and differentiation, whereas MNK-3 cells provide an
attractive in vitro system to study the function of ILC3/LTi cells.
PMID- 25138672
TI - Acupuncture increases the diameter and reorganisation of collagen fibrils during
rat tendon healing.
AB - BACKGROUND: Our previous study showed that electroacupuncture (EA) increases the
concentration and reorganisation of collagen in a rat model of tendon healing.
However, the ultrastructure of collagen fibrils after acupuncture is unknown.
OBJECTIVES: To assess the effect of acupuncture protocols on the ultrastructure
of collagen fibrils during tendon healing. METHODS: Sixty-four rats were divided
into the following groups: non-tenotomised (normal group), tenotomised (teno
group), tenotomised and subjected to manual acupuncture at ST36 (ST36 group),
BL57 (BL57 group) and ST36+BL57 (SB group) and EA at ST36+BL57 (EA group). The
mass-average diameter (MAD) and the reorganisation of collagen fibril diameters
were determined during the three phases of tendon healing (at 7, 14 and 21 days).
RESULTS: The MAD increased during the three phases of healing in the SB group. In
the EA group, MAD increased initially but was reduced at day 21. The
reorganisation of collagen fibrils was improved in the EA and SB groups at days
14 and 21, respectively. EA at day 21 appeared to reduce the reorganisation.
CONCLUSIONS: These results indicate that the use of EA up to day 14 and manual
acupuncture at ST36+BL57 up to day 21 improve the ultrastructure of collagen
fibrils, indicating strengthening of the tendon structure. These data suggest a
potential role for acupuncture in rehabilitation protocols.
PMID- 25138666
TI - CCR2(+)CD103(-) intestinal dendritic cells develop from DC-committed precursors
and induce interleukin-17 production by T cells.
AB - The identification of intestinal macrophages (mphis) and dendritic cells (DCs) is
a matter of intense debate. Although CD103(+) mononuclear phagocytes (MPs) appear
to be genuine DCs, the nature and origins of CD103(-) MPs remain controversial.
We show here that intestinal CD103(-)CD11b(+) MPs can be separated clearly into
DCs and mphis based on phenotype, gene profile, and kinetics. CD64(-)CD103(
)CD11b(+) MPs are classical DCs, being derived from Flt3 ligand-dependent, DC
committed precursors, not Ly6C(hi) monocytes. Surprisingly, a significant
proportion of these CD103(-)CD11b(+) DCs express CCR2 and there is a selective
decrease in CD103(-)CD11b(+) DCs in mice lacking this chemokine receptor.
CCR2(+)CD103(-) DCs are present in both the murine and human intestine, drive
interleukin (IL)-17a production by T cells in vitro, and show constitutive
expression of IL-12/IL-23p40. These data highlight the heterogeneity of
intestinal DCs and reveal a bona fide population of CCR2(+) DCs that is involved
in priming mucosal T helper type 17 (Th17) responses.
PMID- 25138674
TI - Photobleaching reveals heterogeneous stoichiometry for equinatoxin II oligomers.
AB - Equinatoxin II (EqtII), a sea anemone cytolysin, is known to oligomerize to form
pores that spontaneously insert into membranes. Crystallographic and cryo-EM
studies of structurally similar cytolysins offer contradictory evidence for pore
stoichiometry. Here we used single-molecule photobleaching of fluorescently
labeled EqtII to determine the stoichiometry of EqtII oligomers in supported
lipid bilayers. A frequency analysis of photobleaching steps revealed a log
normal distribution of stoichiometries with a mean of 3.4+/-2.3 standard
deviations. Comparison of our experimental data with simulations of fixed
stoichiometries supports our observation of a heterogeneous distribution of EqtII
oligomerization. These data are consistent with a model of EqtII stoichiometry
where pores are on average tetrameric, but with large variation in the number of
subunits in individual pores.
PMID- 25138675
TI - Characterization of an organic solvent-tolerant thermostable glucoamylase from a
halophilic isolate, Halolactibacillus sp. SK71 and its application in raw starch
hydrolysis for bioethanol production.
AB - A halophilic bacterium Halolactibacillus sp. SK71 producing extracellular
glucoamylase was isolated from saline soil of Yuncheng Salt Lake, China. Enzyme
production was strongly influenced by the salinity of growth medium with maximum
in the presence of 5% NaCl. The glucoamylase was purified to homogeneity with a
molecular mass of 78.5 kDa. It showed broad substrate specificity and raw starch
hydrolyzing activity. Analysis of hydrolysis products from soluble starch by thin
layer chromatography revealed that glucose was the sole end-product, indicating
the enzyme was a true glucoamylase. Optimal enzyme activity was found to be at 70
degrees C, pH 8.0, and 7.5% NaCl. In addition, it was highly active and stable
over broad ranges of temperature (0-100 degrees C), pH (7.0-12.0), and NaCl
concentration (0-20%), showing excellent thermostable, alkali stable, and
halotolerant properties. Furthermore, it displayed high stability in the presence
of hydrophobic organic solvents. The purified glucoamylase was applied for raw
corn starch hydrolysis and subsequent bioethanol production using Saccharomyces
cerevisiae. The yield in terms of grams of ethanol produced per gram of sugar
consumed was 0.365 g/g, with 71.6% of theoretical yield from raw corn starch.
This study demonstrated the feasibility of using enzymes from halophiles for
further application in bioenergy production.
PMID- 25138676
TI - Synthesis of composites SBA-15 mesoporous particles carrying oxytocin and
evaluation of their properties, functions, and in vitro biological activities.
AB - Using the organic template method, we have synthesized mesoporous SBA-15
particles and characterized them by scanning electron microscopy and transmission
electron microscopy. The bone metabolism regulating hormone oxytocin (OT) was
selected as a model for preparation of drug/SBA-15 complexes. The process of drug
loading was studied using X-ray diffraction and nitrogen absorption methods.
Optimal drug loading parameters were experimentally investigated. The kinetics of
drug release from the carrier was evaluated. Finally, the extractions of SBA-15
particles were tested for cytotoxicity, in vitro hemolysis, and the direct
attachment toxicity. Our findings suggest that SBA-15 materials have good
biocompatibility. Moreover, we demonstrated that OT/SBA-15 complex can stimulate
alkaline phosphatase activity in osteoblast cells. The study provides fundamental
information for further in vivo drug-carrier testing.
PMID- 25138678
TI - Immunoglobulin G4-related paratesticular fibrous pseudotumor and retroperitoneal
fibrosis: a case report.
AB - A 46-year-old man with a past history of retroperitoneal fibrosis was admitted
with an enlarged, hard right testis. The paratesticular lesion showed
heterogeneous hypoechogenicity on ultrasonography, low signal intensity on T1-
and T2-weighted magnetic resonance imaging (MRI), and lack of diffusion
restriction on diffusion-weighted MRI. Following steroid treatment, the
paratesticular mass was decreased in size on follow-up computed tomography. The
radiologic and clinical features are recognized as a manifestation of
immunoglobulin G4-related sclerosing disease involving the paratesticular region
and retroperitoneum.
PMID- 25138679
TI - Ursodeoxycholic acid, an inhibitor of hepatocyte nuclear factor 1alpha, did not
increase the systemic exposure of pitavastatin.
AB - OBJECTIVE: Pitavastatin, a highly potent inhibitor of 3-hydroxy
methylglutarylcoenzyme A reductase, is a known substrate of OATP1B1.
Ursodeoxycholic acid (UDCA) inhibits OATP1B1 expression by repressing hepatocyte
nuclear factor 1alpha (HNF1alpha). Thus, the effects of UDCA on the
pharmacokinetics of pitavastatin were investigated in healthy subjects. METHODS:
An open-label, 2-phase, parallel study was conducted with 13 healthy volunteers.
In the control phase, after an overnight fast, each subject received a single
dose of 2 mg pitavastatin. After a 1-week washout period, in the UDCA phase,
subjects received a daily oral dose of 600 mg of UDCA (300 mg b.i.d.) for 14
days. On day 15, 2 mg of pitavastatin was administered as described previously
for the control phase. RESULTS: In the UDCA phase, the maximum plasma
concentration (C(max)) of pitavastatin was slightly higher than in the control
phase (48.6 +/- 22.9 ng/mL vs. 42.4 +/- 16.1 ng/mL). However, the overall
pharmacokinetic parameters of pitavastatin and pitavastatin lactone during the
two study phases were not significantly different. CONCLUSIONS: UDCA had no
significant effect on the pharmacokinetics of pitavastatin. These results do not
support the notion that UDCA increases the systemic exposure of OATP1B1 substrate
by inhibiting HNF1alpha and decreasing OATP1B1 transporter expression.
PMID- 25138677
TI - Characterization of dsRed2-positive cells in the doublecortin-dsRed2 transgenic
adult rat retina.
AB - Doublecortin (DCX) is predominantly expressed in neuronal precursor cells and
young immature neurons of the developing and adult brain, where it is involved in
neuronal differentiation, migration and plasticity. Moreover, its expression
pattern reflects neurogenesis, and transgenic DCX promoter-driven reporter models
have been previously used to investigate adult neurogenesis. In this study, we
characterize dsRed2 reporter protein-expressing cells in the adult retina of the
transgenic DCX promoter-dsRed2 rat model, with the aim to identify cells with
putative neurogenic activity. Additionally, we confirmed the expression of the
dsRed2 protein in DCX-expressing cells in the adult hippocampal dentate gyrus.
Adult DCX-dsRed2 rat retinas were analyzed by immunohistochemistry for expression
of DCX, NF200, Brn3a, Sox2, NeuN, calbindin, calretinin, PKC-a, Otx2, ChAT, PSA
NCAM and the glial markers GFAP and CRALBP, followed by confocal laser-scanning
microscopy. In addition, brain sections of transgenic rats were analyzed for
dsRed2 expression and co-localization with DCX, NeuN, GFAP and Sox2 in the cortex
and dentate gyrus. Endogenous DCX expression in the adult retina was confined to
horizontal cells, and these cells co-expressed the DCX promoter-driven dsRed2
reporter protein. In addition, we encountered dsRed2 expression in various other
cell types in the retina: retinal ganglion cells (RGCs), a subpopulation of
amacrine cells, a minority of bipolar cells and in perivascular cells. Since also
RGCs expressed dsRed2, the DCX-dsRed2 rat model might offer a useful tool to
study RGCs in vivo under various conditions. Muller glial cells, which have
previously been identified as cells with stem cell features and with neurogenic
potential, did express neither endogenous DCX nor the dsRed2 reporter. However,
and surprisingly, we identified a perivascular glial cell type expressing the
dsRed2 reporter, enmeshed with the glia/stem cell marker GFAP and colocalizing
with the neural stem cell marker Sox2. These findings suggest the so far
undiscovered existence of perivascular associated cell with neural stem cell-like
properties in the adult retina.
PMID- 25138680
TI - Open-label, 2-period sequential drug interaction study to evaluate the effect of
a 100-mg dose of desvenlafaxine on the pharmacokinetics of tamoxifen when
coadministered in healthy postmenopausal female subjects.
AB - BACKGROUND: Potential drugdrug interactions are a concern for patients taking
tamoxifen. OBJECTIVE: This study was designed to determine the effect of
coadministering desvenlafaxine on tamoxifen pharmacokinetics. MATERIALS AND
METHODS: This open-label, 2-period inpatient and outpatient study enrolled
healthy, postmenopausal women. Period 1, day 1, subjects were administered
tamoxifen 40 mg followed by 23 days of blood sampling for pharmacokinetic
analyses. During period 2, subjects received desvenlafaxine 100 mg/d for 28 days;
a single dose of tamoxifen 40 mg was administered with desvenlafaxine 100 mg on
day 7, followed by 23 days of blood sampling. Pharmacokinetics of tamoxifen and
its metabolites (AUC over infinite time (AUC(inf)), AUC to the last measurable
concentration (AUC(last)), peak plasma concentration (C(max)) were compared for
monotherapy vs. combination therapy using the ratio of adjusted mean differences.
A superposition method was used in the statistical analysis of N-desmethyl
tamoxifen and endoxifen to address the carry-over observed for those metabolites.
The test for interaction was considered negative if the 90% confidence intervals
(CIs) for the ratios were within 80 - 125%. RESULTS: Coadministration of
tamoxifen with steady-state desvenlafaxine did not alter tamoxifen AUC(inf),
AUC(last), and C(max), as reflected by the ratio of adjusted geometric means (90%
CIs) of 100.7% (96.7%, 104.9%), 103.5% (100.2%, 106.9%), and 99.4% (94.0%,
105.2%), respectively. Similarly, coadministration did not alter 4-hydroxy-
tamoxifen and N-desmethyl-amoxifen pharmacokinetics. The 11.8% (88.2% (82.6%,
94.2%)) and 8.0% (92.0% (84.7%, 100.0%)) decreases in endoxifen AUC(last) and
C(max), respectively, were not significant (90% CIs fell wholly within the
prespecified acceptance range). CONCLUSIONS: Steady-state desvenlafaxine 100 mg
did not affect tamoxifen pharmacokinetics. For women treated with tamoxifen,
desvenlafaxine may represent a safe and effective treatment unlikely to alter
tamoxifen efficacy.
PMID- 25138681
TI - Implications of different application sites on the bioavailability of a
transdermal contraceptive patch containing ethinyl estradiol and gestodene: an
open-label, randomized, crossover study.
AB - OBJECTIVES: A novel once-a-week contraceptive patch delivers the same systemic
exposure seen with a combined oral contraceptive pill containing 0.02 mg ethinyl
estradiol (EE) and 0.06 mg gestodene (GSD). This study evaluated the relative
bioavailability of EE and GSD after application of this patch to three different
sites. METHODS: In this phase I, open-label, randomized, intra-individual
comparison, crossover study, 43 women (aged 18 - 45 years) were randomized to one
of six treatment sequences. Patches were applied to two test sites (buttocks and
outer, upper arm) and one comparator site (lower abdomen). In each treatment
period, four patches were worn for 7 days each, followed by a 7-day, patch-free
interval. The primary objective was to investigate the relative bioavailability
of transdermally administered EE and GSD between test and comparator sites using
the primary variable area under the concentration- time curve (AUC(0-168)) during
week 4 of each period. RESULTS: Of the 43 women who were randomized, 43 were
included in the set for safety evaluation and 40 were included in the set for
pharmacokinetic (PK) analysis. Three subjects were excluded from the PK analysis
as they failed to complete the study. AUC(0-168) for EE and GSD were equal when
the patch was applied to buttocks or abdomen (AUC(0-168) ratios: EE, 1.07 (94%
confidence interval, CI: 0.994 - 1.16); GSD, 1.02 (94% CI: 0.946 - 1.10)).
Relative bioavailabilities for EE and GSD were 31% and 24% higher, respectively,
for arm vs. abdomen. AUC(0-168) 94% CI for the arm/abdomen ratio exceeded the pre
defined bioequivalence range of 80 - 125% (EE: 1.21 - 1.42; GSD: 1.15 - 1.34).
Other PK parameters were correspondingly higher for arm vs. buttocks or abdomen.
Patch adhesion and tolerability were good, with no relevant differences between
sites. CONCLUSION: Differences in systemic EE/GSD exposure following patch
application to the outer, upper arm vs. lower abdomen and buttocks are unlikely
to be clinically relevant, and there were no relevant safety concerns.
PMID- 25138682
TI - Pharmacokinetics of vorapaxar and its metabolite following oral administration in
healthy Chinese and American subjects.
AB - AIM: Vorapaxar is a proteaseactivated receptor (PAR)-1 antagonist being developed
for the prevention and treatment of thrombotic vascular events. To evaluate
race/ethnic differences between Caucasians and Chinese in the pharmacokinetics of
vorapaxar and its active metabolite SCH 2046273 (M20) or in the metabolite/parent
ratio, we conducted a cross-study comparison on pharmacokinetic data of vorapaxar
and M20 obtained from two similarly designed studies: one in healthy Chinese
subjects and the other in a healthy Western (United States, [U.S.]) population.
METHODS: The pharmacokinetic profiles of vorapaxar and M20 were characterized
using open label, two treatment parallel group designs in men and women aged 18 -
45 years. Vorapaxar was administered orally as a single dose of 40 mg in Chinese
subjects (n = 14) or 120 mg in U.S. subjects (n = 14), or 2.5 mg QD for 6 weeks
in both studies (Chinese, n = 14; U.S., n = 23). RESULTS: Vorapaxar was rapidly
absorbed in both Chinese and U.S. subjects. Vorapaxar and M20 had similar
elimination half-lives. The range of metabolite/parent ratios after single dose
or daily administration was largely overlapped in Chinese and U.S. subjects.
Steady state was attained by day 21 for vorapaxar and M20 in both race/ethnic
groups. The accumulation ratios for vorapaxar and M20 during daily administration
were similar in Chinese and U.S. subjects. Vorapaxar was well-tolerated in
Chinese and U.S. subjects. CONCLUSION: The pharmacokinetic profiles of vorapaxar
and M20 and the metabolite/parent ratios in healthy Chinese were generally
comparable to those in a healthy Western population.
PMID- 25138683
TI - Ultrafast photoswitching in a copper-nitroxide-based molecular magnet.
AB - Molecular compounds with photoswitchable magnetic properties have been
intensively investigated over the last decades due to their prospective
applications in nanoelectronics, sensing and magnetic data storage. The family of
copper-nitroxide-based molecular magnets represents a new promising type of
photoswitchable compounds. We report the first study of these appealing systems
using femtosecond optical spectroscopy. We unveil the mechanism of ultrafast (<50
fs) spin state photoswitching and establish its principal differences compared to
other photoswitchable magnets. On this basis, we propose potential advantages of
copper-nitroxide-based molecular magnets for the future design of ultrafast
magnetic materials.
PMID- 25138684
TI - Development of necrotising fasciitis in a patient treated for rheumatoid
arthritis with tocilizumab.
PMID- 25138685
TI - Reliability and validity of the pain on movement questionnaire (POM) in chronic
neck pain.
AB - OBJECTIVE: This analysis aimed to determine reliability, validity, and
responsiveness of the pain on movement (POM) questionnaire, an instrument
developed to determine pain intensity induced by head movement. DESIGN: Data from
nine randomized controlled trials for the treatment of chronic nonspecific neck
pain were reanalyzed to determine reliability and validity of the POM
questionnaire. METHODS: POM was assessed as ratings of pain intensity induced by
head movement in six different directions. The instrument's structure was
assessed using a factor analysis. Reliability (internal consistency) was
determined using Cronbach's alpha, and validity (convergent validity) was
determined by correlating the POM with pain at rest on a visual analog scale
(VAS), the neck disability index (NDI), quality of life (short-form 36 health
survey questionnaire [SF-36]) and range of motion. Responsiveness was indicated
by sensitivity to changes over time in a subsample of 49 patients. RESULTS:
Overall, 482 patients (mean age 50.3 +/- 12.4 years, 72.3% female) were included
in the analysis, and 458 of them provided complete data set for the POM. Average
POM was 43.9 +/- 20.8 mm on the VAS. The POM showed very good reliability as
indicated by high internal consistency and moderate validity as indicated by
significant correlations with the pain at rest, the NDI, and the SF-36. No
correlations were found for POM with range of motion. The POM further proved to
be responsive as it was sensitive to changes over time, and those changes were
correlated to changes in pain intensity and NDI. CONCLUSIONS: The POM seems to be
a reliable and valid instrument to assess POM in patients with chronic
nonspecific neck pain.
PMID- 25138686
TI - PML nuclear bodies: regulation, function and therapeutic perspectives.
AB - PML nuclear bodies (NBs) were first described by electron microscopy and
rediscovered through their treatment-reversible disruption in a rare leukaemia.
They recruit multiple partner proteins and now emerge as interferon- and
oxidative stress-responsive sumoylation factories. NBs mediate interferon-induced
viral restriction, enhance proteolysis, finely tune metabolism and enforce stress
induced senescence. Apart from being markers of cellular stress, PML NBs could be
harnessed pharmacologically in a number of conditions, including cancer, viral
infection or neurodegenerative diseases.
PMID- 25138687
TI - Another casualty of sibling fixed-effects analysis of education and health: an
informative null, or null information?
PMID- 25138688
TI - From policy to practice: implementing frontline community health services for
substance dependence--study protocol.
AB - BACKGROUND: Substance abuse is a worldwide public health concern. Extensive
scientific research has shown that screening and brief interventions for
substance use disorders administered in primary care provide substantial benefit
at relatively low cost. Frontline health clinicians are well placed to detect and
treat patients with substance use disorders. Despite effectiveness shown in
research, there are many factors that impact the implementation of these
practices in real-world clinical practice. Recently, the Ministry of Health and
Social Services in Quebec, Canada, issued two policy documents aimed at
introducing screening and early intervention for substance abuse into frontline
healthcare clinics in Quebec. The current research protocol was developed in
order to study the process of implementation of evidence-based addiction
treatment practices at three primary care clinics in Montreal (Phase 1). In
addition, the research protocol was designed to examine the efficacy of overall
policy implementation, including barriers and facilitators to addictions program
development throughout Quebec (Phase 2). METHODS/DESIGN: Phase 1 will provide an
in-depth case study of knowledge translation and implementation. The study
protocol will utilize an integrated knowledge translation strategy to build
collaborative mechanisms for knowledge exchange between researchers, addiction
specialists, and frontline practitioners (guided by the principles of
participatory-action research), and directly examine the process of knowledge
uptake and barriers to transfer using both qualitative and quantitative
methodologies. Evaluation will involve multiple measures, time points and
domains; program uptake and effectiveness will be determined by changes in
healthcare service delivery, sustainability and outcomes. In Phase 2, qualitative
methods will be utilized to examine the contextual facilitators and barriers that
frontline organizations face in implementing services for substance dependence.
Phase 2 will provide the first study exploring the wide-scale implementation of
frontline services for substance dependence in the province of Quebec and yield
needed information about how to effectively implement mandated policies into
clinical practice and impact public health. DISCUSSION: Findings from this
research program will contribute to the understanding of factors associated with
implementation of frontline services for substance dependence and help to inform
future policy and organizational support for the implementation of evidence-based
practices.
PMID- 25138689
TI - Mean platelet volume is a prognostic factor in patients with acute kidney injury
requiring continuous renal replacement therapy.
AB - PURPOSE: Platelet size has been demonstrated to reflect platelet activity and to
predict poor clinical outcomes in patients with cardiovascular disease. However,
the prognostic value of platelet size for mortality has not been studied in
patients with acute kidney injury (AKI). MATERIALS AND METHODS: A total of 349
patients who received continuous renal replacement therapy (CRRT) for AKI between
August 2009 and October 2011 were divided into 2 groups based on the median mean
platelet volume (MPV) at the time of CRRT initiation. Twenty-eight-day mortality
rate was determined using Kaplan-Meier plots and time-dependent receiver
operating characteristic curves were constructed. In addition, multivariate Cox
analysis for mortality was used to evaluate the independent prognostic value of
MPV. RESULTS: The mean age was 61.3 years, and 218 patients (62.5%) were male. At
the initiation of CRRT, MPV level was inversely correlated with platelet count,
whereas it was positively associated with Acute Physiology and Chronic Health
Evaluation II scores. During the study period, 231 deaths (66.2%) occurred.
Kaplan-Meier curve showed that 28-day all-cause mortality was significantly
higher in patients with MPV>=10.2 fL compared with those with MPV<10.2 fL
(P<.001). Moreover, Cox regression analysis revealed that MPV was an independent
predictor for 28-day all-cause mortality after adjustment of age, age-adjusted
Charlson Comorbidity Index, cause of AKI, platelet count, Acute Physiology and
Chronic Health Evaluation II score, presence of malignancy, albumin, and C
reactive protein (hazard ratio, 1.080; 95% confidence interval, 1.010-1.155;
P=.023). CONCLUSION: Mean platelet volume at the time of CRRT initiation may be
an inexpensive and useful predictor for 28-day all-cause mortality in patients
with AKI requiring CRRT.
PMID- 25138690
TI - Association between transient acute kidney injury and morbidity and mortality
after lung transplantation: a retrospective cohort study.
AB - PURPOSE: Acute kidney injury (AKI) is a common occurrence after lung
transplantation (LTx). Whether transient AKI or early recovery is associated with
improved outcome is uncertain. Our aim was to describe the incidence, factors,
and outcomes associated with transient AKI after LTx. MATERIALS AND METHODS: We
performed a retrospective cohort study of all adult recipients of LTx at the
University of Alberta between 1990 and 2011. Our primary outcome transient AKI
was defined as return of serum creatinine below Kidney Disease-Improving Global
Outcome AKI stage I within 7days after LTx. Secondary outcomes included
occurrence of postoperative complications, mortality, and long-term kidney
function. RESULTS: Of 445 LTx patients enrolled, AKI occurred in 306 (68.8%)
within the first week after LTx. Of these, transient AKI (or early recovery)
occurred in 157 (51.3%). Transient AKI was associated with fewer complications
including tracheostomy (17.2% vs 38.3%; P<.001), reintubation (16.4% vs 41.9%;
P<.001), decreased duration of mechanical ventilation (median [interquartile
range], 69 [41-142] vs 189 [63-403] hours; P<.001), and lower rates of chronic
kidney disease at 3 months (28.5% vs 51.1%, P<.001) and 1 year (49.6% vs 66.7%,
P=.01) compared with persistent AKI. Factors independently associated with
persistent AKI were higher body mass index (per unit; odds ratio [OR], 0.91; 95%
confidence interval, 0.85-0.98; P=.01), cyclosporine use (OR, 0.29; 0.12-0.67;
P=.01), longer duration of mechanical ventilation (per hour [log transformed];
OR, 0.42; 0.21-0.81; P=.01), and AKI stages II to III (OR, 0.16; 0.08-0.29;
P<.001). Persistent AKI was associated with higher adjusted hazard of death
(hazard ratio, 1.77 [1.08-2.93]; P=.02) when compared with transient AKI (1.44
[0.93-2.19], P=.09) and no AKI (reference category), respectively. CONCLUSIONS:
Transient AKI after LTx is associated with fewer complications and improved
survival. Among survivors, persistent AKI portends an increased risk for long
term chronic kidney disease.
PMID- 25138693
TI - Cytoarchitecture of the telencephalon in the coral reef multiband Butterflyfish (
Chaetodon multicinctus : Perciformes).
AB - Detailed neuroanatomical studies of model species are necessary to facilitate
comparative experiments which test hypotheses relevant to brain evolution and
function. Butterflyfishes (Chaetodontidae) boast numerous sympatric species that
differ in social behavior, aggression and feeding ecology. However, the ability
to test hypotheses relevant to brain function in this family is hindered by the
lack of detailed neural descriptions. The cytoarchitecture of the telencephalon
in the monogamous and territorial multiband butterflyfish, Chaetodon
multicinctus, was determined with Nissl-stained serial sections and an
immunohistochemical analysis of arginine vasotocin (AVT), serotonin, substance P
and tyrosine hydroxylase. The ventral telencephalon was similar to that of other
perciform fishes studied, with one major difference. A previously undescribed
postcommissural region, the cuneate nucleus, was identified and putatively
assigned to the ventral telencephalon. While the function of this nucleus is
unknown, preliminary studies indicate that it may be part of a behaviorally
relevant subpallial neural circuit that is modulated by AVT. The dorsal
telencephalon consisted of 15 subdivisions among central, medial, lateral, dorsal
and posterior zones. Several regions of the dorsal telencephalon of C.
multicinctus differed from many other perciform fishes examined thus far. The
nucleus taenia was in a more caudal position, and the central and lateral zones
were enlarged. Within the lateral zone, an unusual third, ventral subdivision and
a large-celled division were present. One hypothesis is that the enlarged ventral
subdivision of the lateral zone (potential hippocampus homolog) relates to an
enhancement of spatial learning or olfactory memory, which are important for this
coral reef fish. This study provides the neuroanatomical basis for future
comparative and evolutionary studies of brain organization and neuropeptide
distributions, physiological studies of neural processing and insight into the
complex social behavior of butterflyfishes.
PMID- 25138692
TI - Effect of enamel protective agents on shear bond strength of orthodontic
brackets.
AB - BACKGROUND: This paper aimed to study the effect of two enamel protective agents
on the shear bond strength (SBS) of orthodontic brackets bonded with conventional
and self-etching primer (SEP) adhesive systems. METHODS: The two protective
agents used were resin infiltrate (ICON) and Clinpro; the two adhesive systems
used were self-etching primer system (Transbond Plus Self Etching Primer +
Transbond XT adhesive) and a conventional adhesive system (37% phosphoric acid
etch + Transbond XT primer + Transbond XT adhesive ). Sixty premolars divided
into three major groups and six subgroups were included. The shear bond strength
was tested 72 h after bracket bonding. Adhesive remnant index scores (ARI) were
assessed. Statistical analysis consisted of a one-way ANOVA for the SBS and
Kruskal-Wallis test followed by Mann-Whitney test for the ARI scores. RESULTS: In
the control group, the mean SBS when using the conventional adhesive was 21.1 +/-
7.5 MPa while when using SEP was 20.2 +/- 4.0 MPa. When ICON was used with the
conventional adhesive system, the SBS was 20.2 +/- 5.6 MPa while with SEP was
17.6 +/- 4.1 MPa. When Clinpro was used with the conventional adhesive system,
the SBS was 24.3 +/- 7.6 MPa while with SEP was 11.2 +/- 3.5 MPa. Significant
differences in the shear bond strength of the different groups (P = .000) was
found as well as in the ARI scores distribution (P = .000). CONCLUSION: The type
of the adhesive system used to bond the orthodontic brackets, either conventional
or self-etching primer, influenced the SBS, while the enamel protective material
influenced the adhesive remnant on the enamel surface after debonding.
PMID- 25138694
TI - How does obesity affect fertility in men - and what are the treatment options?
AB - Adiposity is associated with reduced fertility in men. The aetiology is
multifactorial, with obese men at greater risk of suffering from impaired
spermatogenesis, reduced circulating testosterone levels, erectile dysfunction
and poor libido. The diagnosis and treatment of reduced fertility observed in
obese men therefore requires insight into the underlying pathology, which has
hormonal, mechanical and psychosocial aspects. This article summarises the
current epidemiological, experimental and clinical trial evidence from the
perspective of a practicing clinician. The following conclusions and
recommendations can be drawn: Obesity is associated with low serum testosterone
concentrations, but treatment with exogenous testosterone is likely to adversely
impact on fertility. It is important to discuss this with men prior to initiation
of testosterone therapy. Obesity adversely affects sperm concentration and may
affect sperm quality. However, whether or not weight loss will correct these
factors remain to be established. Oestrogen receptor modulators (and aromatase
inhibitors) are unlicensed in the treatment for male hypogonadism and/or
infertility. These treatments should hence be considered experimental approach
until ongoing clinical trials report their outcomes.
PMID- 25138695
TI - Coacervate delivery systems for proteins and small molecule drugs.
AB - Coacervates represent an exciting new class of drug delivery vehicles, developed
in the past decade as carriers of small molecule drugs and proteins. This review
summarizes several well-described coacervate systems, including: i) elastin-like
peptides for delivery of anticancer therapeutics; ii) heparin-based coacervates
with synthetic polycations for controlled growth factor delivery; iii)
carboxymethyl chitosan aggregates for oral drug delivery; iv) Mussel adhesive
protein and hyaluronic acid coacervates. Coacervates present advantages in their
simple assembly and easy incorporation into tissue engineering scaffolds or as
adjuncts to cell therapies. They are also amenable to functionalization such as
for targeting or for enhancing the bioactivity of their cargo. These new drug
carriers are anticipated to have broad applications and noteworthy impact in the
near future.
PMID- 25138696
TI - Effects of ventral pallidal D1 dopamine receptor activation on memory
consolidation in morris water maze test.
AB - In the present experiments, in adult male Wistar rats, the effect of
microinjection of the D1 dopamine receptor agonist SKF38393 into the ventral
pallidum on memory consolidation, as well as on resistance of the resulting
memory trace against extinction were investigated in Morris water maze test.
SKF38393 was applied in three doses (0.1, 1.0 or 5.0MUg in 0.4MUl physiological
saline, respectively). To clarify whether the effect of the agonist was specific,
in a separate group of animals, the D1 dopamine receptor antagonist SCH23390
(5.0MUg in 0.4MUl physiological saline) was administered 15min prior to 1.0MUg
agonist treatment. In another group of animals, the same dose of antagonist was
applied by itself. The two lower doses (0.1 and 1.0MUg) of the agonist
accelerated memory consolidation relative to controls and increased the stability
of the consolidated memory trace against extinction. Antagonist pretreatment
eliminated the effects of the agonist, thus confirming that the effect was
selectively specific to D1 dopamine receptors. Our findings indicate that the
ventral pallidal D1 dopamine receptors are intimately involved in the control of
the consolidation processes of spatial memory.
PMID- 25138697
TI - Frequency-dependent changes in the amplitude of low-frequency fluctuations in
subcortical ischemic vascular disease (SIVD): a resting-state fMRI study.
AB - Resting-state functional magnetic resonance imaging (RS-fMRI) allowed researchers
to detect intrinsic brain activity during rest and has been considered an
analytical tool for evaluation of dementia. Previously, subcortical ischemic
vascular disease (SIVD) has been found decreased amplitude low-frequency
fluctuations (ALFF) in a widely frequency range (0.01-0.08Hz) in the bilateral
precuneus and increased ALFF values in the bilateral anterior cingulate cortex
(ACC), left insula and hippocampus, which showed significant correlations with
the cognitive performance. In this study we analyzed the ALFF of 30 patients with
SIVD in two different frequency bands (slow-5: 0.01-0.027Hz; slow-4: 0.027
0.073Hz). In the slow-5 band, SIVD patients compared with controls exhibited
significant higher ALFF in the bilateral anterior cingulate cortex, right putamen
and right supplementary motor area, while lower ALFF in the right precuneus and
right angular gyrus. A close correlation was found between the ALFF value of the
right angular gyrus and ADL scores. In the slow-4 band, SIVD patients only
exhibited increased ALFF in the bilateral anterior cingulate cortex, right
putamen, left fusiform gyrus, and no correlation with cognitive scores was found.
Our data demonstrate that SIVD patients have widespread abnormal intrinsic neural
oscillations, which are dependent on specific frequency bands. ALFF of right
angular gyrus at slow-5 band is more specific for SIVD and may be a useful tool
to help SIVD diagnosis.
PMID- 25138698
TI - King-Devick test normative reference values for professional male ice hockey
players.
AB - The King-Devick (K-D) test, a measure of processing speed, visual tracking, and
saccadic eye movements, has shown promise as a supplemental screening test
following concussion. However, limited normative data for this test have been
published.The K-D test was administered to 185 professional ice hockey players as
a preseason baseline test in seasons 2012-2013 and 2013-2014. Their average age
was 23.8 years (median = 22.0 years, range = 16-40 years). The average K-D score
was 40.0 s (SD = 6.1 s, range = 24.0-65.7 s). K-D test performance showed no
association with age, education, or the number of self-reported previous
concussions in this sample. The association between trials 1 and 2 of the K-D
test was good (ICC = 0.92, Pearson = 0.93). Normative values of the K-D test for
professional male ice hockey players are reported. K-D test performance did not
vary by age, education, or concussion history in this study.
PMID- 25138699
TI - Dietary LC-PUFA in iron-deficient anaemic pregnant and lactating guinea pigs
induce minor defects in the offsprings' auditory brainstem responses.
AB - OBJECTIVES: We previously demonstrated that a mild pre-natal/early post-natal
iron-deficient anaemic (IDA) diet devoid of long-chain polyunsaturated fatty
acids (LC-PUFA) affected development, neurophysiology, and cerebral lipid
biochemistry of the guinea pigs' progeny. Impacts of dietary LC-PUFA on altered
cerebral development resulting from pre-natal IDA are unknown. To address this
health issue, impacts of mild gestational IDA in the presence of dietary LC-PUFA
on the offsprings' neural maturation were studied in guinea pigs using auditory
brainstem responses (ABRs) and assessments of brain fatty acids (FAs). METHODS:
Female guinea pigs (n = 10/group) were fed an iron sufficient (IS) or IDA diet
(146 and 12.7 mg iron/kg, respectively) with physiological amounts of LC-PUFA,
during the gestation and lactation periods. From post-natal day (PNd) 9 onwards,
the IS + PUFA diet was given to both groups of weaned offspring. Cerebral tissue
and offsprings' ABR were collected on PNd24. RESULTS: There was no difference in
peripheral and brainstem transmission times (BTTs) between IS + PUFA and IDA +
PUFA siblings (n = 10/group); the neural synchrony was also similar in both
groups. Despite the absence of differences in auditory thresholds, IDA + PUFA
siblings demonstrated a sensorineural hearing loss in the extreme range of
frequencies (32, 4, and 2 kHz), as well as modified brain FA profiles compared to
the IS + PUFA siblings. DISCUSSION: The present study reveals that siblings born
from dams exposed to a moderate IDA diet including balanced physiological LC-PUFA
levels during pregnancy and lactation demonstrate minor impairments of ABR
compared to the control siblings, particularly on the auditory acuity, but not on
neural synchrony, auditory nerve velocity and BTT.
PMID- 25138700
TI - Decreased BMP2 signal in GIT1 knockout mice slows bone healing.
AB - Endochondral ossification, an important stage of fracture healing, is regulated
by a variety of signaling pathways. Transforming growth factor beta (TGFbeta)
superfamily plays important roles and comprises TGFbetas, bone morphogenetic
proteins (BMPs), and growth differentiation factors. TGFbetas primarily regulate
cartilage formation and endochondral ossification. BMP2 shows diverse efficacy,
from the formation of skeleton and extraskeletal organs to the osteogenesis and
remodeling of bone. G-protein-coupled receptor kinase 2-interacting protein-1
(GIT1), a shuttle protein in osteoblasts, facilitates fracture healing by
promoting bone formation and increasing the secretion of vascular endothelial
growth factor. Our study examined whether GIT1 regulates fracture healing through
the BMP2 signaling pathway and/or through the TGFbeta signaling pathway. GIT1
knockout (KO) mice exhibited delayed fracture healing, chondrocyte accumulation
in the fracture area, and reduced staining intensity of phosphorylated Smad1/5/8
(pSmad1/5/8) and Runx2. Endochondral mineralization diminished while the staining
intensity of phosphorylated Smad2/3 (pSmad2/3) showed no significant change. Bone
marrow mesenchymal stem cells extracted from GIT1 KO mice showed a decline of
pSmad1/5/8 levels and of pSmad1/5/8 translocated into the cell nucleus after BMP2
stimulus. We detected no significant change in the pSmad2/3 level after TGFbeta1
stimulus. Data obtained from reporter gene analysis of C3H10T1/2 cells cultured
in vitro confirmed these findings. GIT1-siRNA inhibited transcription in the cell
nucleus via pSmad1/5/8 after BMP2 stimulus but had no significant effect on
transcription via pSmad2/3 after TGFbeta1 stimulus. Our results indicate that
GIT1 regulates Smad1/5/8 phosphorylation and mediates BMP2 regulation of Runx2
expression, thus affecting endochondral ossification at the fracture site.
PMID- 25138701
TI - TGF-beta1 enhances SDF-1-induced migration and tube formation of choroid-retinal
endothelial cells by up-regulating CXCR4 and CXCR7 expression.
AB - Stromal derived factor (SDF)-1 has been confirmed to regulate angiogenesis in
choroidal neovascularization formation via its two receptors, CXC chemokine
receptors 4 (CXCR4) and 7 (CXCR7). Previous studies found that there is cross
talk between the transforming growth factor beta (TGF-beta) and SDF-1 pathways in
some types of immune or tumor cells, but much less is known about this
interaction in endothelial cells. This study investigated the effects of TGF
beta1 on CXCR4 and CXCR7 expression as well as SDF-1-induced migration and tube
formation in choroid-retinal endothelial (RF/6A) cells. RF/6A cells were treated
with recombinant TGF-beta1 at various concentrations and time points. Real-time
PCR and Western blotting were used to examine the mRNA and protein levels of
CXCR4 and CXCR7. In addition, transwell migration and Matrigel tube formation
analyses were performed to investigate the role of TGF-beta1 pretreatment in SDF
1-induced RF/6A cell migration and tube formation. Our results showed that
treatment with recombinant human TGF-beta1 enhanced the CXCR4 and CXCR7 levels in
time- and dose-dependent manners. The increased CXCR4 and CXCR7 expression
resulted in increased SDF-1-induced RF/6A cell migration and tube formation. In
addition, the transcriptional regulation of CXCR4 and CXCR7 by TGF-beta1 was
found to be mediated by phosphorylation of the extracellular signal-related
kinase1/2 pathway. Altogether, these results demonstrate that a cross-talk exists
between the TGF-beta1 and SDF-1 pathways in choroid-retinal endothelial cells,
reflecting a novel molecular mechanism that explains the pro-angiogenic effects
of TGF-beta1 and possibly provides new perspectives for the treatment of CNV
associated diseases.
PMID- 25138702
TI - Apollon/Bruce is upregulated by Humanin.
AB - Humanin, a short bioactive peptide, inhibits a variety of cell deaths. Humanin
mediated inhibition of neuronal cell death, caused by an Alzheimer's disease (AD)
linked mutant gene occurs via binding of Humanin to its heterotrimeric Humanin
receptor (htHNR), which results in the activation of the Janus-associated kinases
(JAKs) and signal transducer and activator and transcription 3 (STAT3) signaling
pathway. A previous study demonstrated that the Humanin-induced activation of the
htHNR/JAK2/STAT3 signaling pathway leads to increased expression of SH3 domain
binding protein 5 (SH3BP5), which is an essential effector of Humanin's anti-cell
death activity in some cultured neuronal cells. However, it remains unknown
whether SH3BP5 is the sole effector of the Humanin signaling pathway via
htHNR/JAKs/STAT3. Here we show that the Humanin signaling pathway via
htHNR/JAKs/STAT3 increased the expression levels of mRNA and protein of
Apollon/Bruce, an unusual member of the inhibitors of apoptosis proteins, and
that overexpression of Apollon/Bruce inhibits neuronal death, caused by a London
type familial AD-linked mutant (V642I) of amyloid beta precursor protein.
Overall, the results indicate that expression of Apollon/Bruce is upregulated by
Humanin, and Apollon/Bruce could be an effector of Humanin in a context-dependent
manner.
PMID- 25138703
TI - Coordinated regulation of autophagy and apoptosis determines endothelial cell
fate during Dengue virus type 2 infection.
AB - Dengue is the most prevalent mosquito-borne viral disease in tropical regions.
Severe cases may progress to Dengue hemorrhagic fever, suggesting vascular
endothelial dysfunction in disease pathogenesis. In our previous study, we found
that Dengue virus type 2 (DENV2) induced apoptosis of vascular endothelial cells
via FasL/Fas- and XIAP-associated factor 1 (XAF1)-dependent pathways. In this
paper, we demonstrate that DENV2 can induce autophagy in primary human umbilical
vein endothelial cells (HUVECs) and the human umbilical vein endothelial cell
line EA.hy926. Inhibition of autophagy with 3-methyl adenine promoted apoptosis,
while inhibition of apoptosis with Z-VAD-FMK facilitated autophagy in DENV2
infected HUVECs and EA.hy926 cells. Interferon-alpha-inducible protein 6 (IFI6),
a putative apoptosis regulator, inhibited DENV2-induced autophagy in EA.hy926
cells, while XAF1, an inhibitor of anti-apoptotic XIAP, facilitated autophagy.
Molecular regulators of apoptosis and autophagy interact at multiple levels to
determine cell fate. Our data suggest that XAF1 and IFI6 are involved in
regulating the balance between autophagy and apoptosis in DENV2-infected
endothelial cells.
PMID- 25138706
TI - Comparative evaluation of seven different sample treatment approaches for large
scale multiclass sport drug testing in urine by liquid chromatography-mass
spectrometry.
AB - Sample preparation is a critical step in large-scale multiclass analysis such as
sport drug testing. Due to the wide heterogeneity of the analytes and the
complexity of the matrix, the selection of a correct sample preparation method is
essential, looking for a compromise between good recoveries for most of the
analytes and cleanliness of the extract. In the present work, seven sample
preparation procedures based on solid-phase extraction (SPE) (with 5 different
cartridges), liquid-liquid extraction (LLE) and sorbent-supported liquid
extraction (SLE) were evaluated for multiclass sport drug testing in urine. The
selected SPE sorbents were polymeric cartridges Agilent PLEXATM and Oasis HLBTM,
mixed mode cation and anion exchange cartridges Oasis MAXTM and MCXTM, and C18
cartridges. LLE was performed using tert-butyl methyl ether and SLE was carried
out using Agilent Chem ElutTM cartridges. To evaluate the proposed extraction
procedures, a list of 189 compounds were selected as representative from
different groups of doping agents, including 34 steroids, 14
glucocorticosteroids, 24 diuretics and masking agents, 11 stimulants, 9 beta
agonist, 16 beta-blockers, 6 Selective Estrogen Receptors Modulators (SERMs), 24
narcotics and 22 other drugs of abuse/sport drugs. Blank urine samples were
spiked at two levels of concentration, 2.5 and 25MUgL(-1) and extracted with the
different extraction protocols (n=6). The analysis of the extracts was carried
out by liquid chromatography electrospray time-of-flight mass spectrometry. The
use of solid-phase extraction with polymer cartridges provided high recoveries
for most of the analytes tested and was found the more suitable method for this
type of application given the additional advantages such as low sample and
solvent consumption along with increased automation and throughput.
PMID- 25138704
TI - Epigenetic modifications and NF-kappaB pathway activity in Cu,Zn-SOD-deficient
mice.
AB - The aim of this study was to examine the possible impact of Cu,Zn-SOD deficiency
on the level of epigenetic modifications in different mouse tissues, and the
relationship between these modifications and the NF-kappaB transcription factor
activity. Cu,Zn-SOD deficiency did not influence the level of 5mdC or 5hmdC in
the analyzed tissues. Statistically significant organ-/tissue-specific
differences between the levels of 5mdC and 5hmdC were demonstrated within each
genotype. Also correlations between analyzed parameters pointed to wide
tissue/genotype variety; we observed a positive correlation between 5mdC and NF
kB proteins, p50 and RelA, in the liver of wild mice, as well as an inverse
correlation between 5mdC and p65 in the brain of Cu,Zn-SOD-deficient animals.
Moreover, a positive correlation was revealed between 5mdC and 5hmdC in the liver
and brain of knockout mice. As the highest levels of both 5mdC and 5hmdC were
observed in the brains of analyzed animals regardless of their genotype, and
lower, comparable to each other, levels of these modifications were shown in the
kidney and liver, active demethylation process seems to be tissue-/organ-specific
and does not necessarily rely solely on the redox/oxidation state of cells.
According to the most likely scenario, various tissues may differ in terms of
their metabolic rates, which has potential influence on cofactors, and
consequently on the activity of TET enzymes or activation of TET-independent
mechanisms.
PMID- 25138707
TI - Dynamic high performance liquid chromatography on chiral stationary phases. Low
temperature separation of the interconverting enantiomers of diazepam,
flunitrazepam, prazepam and tetrazepam.
AB - Diazepam and the structurally related 1,4-benzodiazepin-2-ones tetrazepam,
prazepam and flunitrazepam are chiral molecules because they adopt a ground state
conformation featuring a non-planar seven membered ring devoid of any reflection
symmetry element. The two conformational enantiomers of this class of
benzodiazepines interconvert rapidly at room temperature by a simple ring
flipping process. Low temperature HPLC on the Whelk-O1 chiral stationary phase
allowed us to separate the conformational enantiomers of diazepam and of the
related 1,4-benzodiazepin-2-ones, under conditions where the interconversion rate
is sufficiently low, compared to the chromatographic separation rate. Diazepam,
tetrazepam and prazepam showed temperature dependent dynamic HPLC profiles with
interconversion plateaus indicative of on-column enantiomer interconversion
(enantiomerization) in the temperature range between -10 degrees C and -35
degrees C, whereas for flunitrazepam on-column interconversion was observed at
temperatures between -40 degrees C and -66 degrees C. Simulation of exchange
deformed HPLC profiles using a computer program based on the stochastic model
yielded the apparent rate constants for the on-column enantiomerization and the
corresponding free energy activation barriers. At -20 degrees C the
enantiomerization barriers, DeltaG(?), for diazepam, prazepam and tetrazepam were
determined to be in the range 17.6-18.7 kcal/mol. At -55 degrees C DeltaG(?) for
flunitrazepam was determined to be in the 15.6-15.7 kcal/mol range. The
experimental dynamic chromatograms and the corresponding interconversion barriers
reported in this paper call for a reinterpretation of previously published
results on the HPLC behavior of diazepam on chiral stationary phases.
PMID- 25138705
TI - Hormonal regulation of the cytokine microenvironment in the mammary gland.
AB - The mammary gland is a unique organ that undergoes hormone-driven developmental
changes over the course of the ovarian cycle during adult life. Macrophages play
a role in regulating cellular turnover in the mammary gland and may affect cancer
susceptibility. However, the immune microenvironment that regulates macrophage
function has not been described. Hormonal regulation of the cytokine
microenvironment across the ovarian cycle was explored using microbead multiplex
assay for 15 cytokines in mammary glands from C57Bl/6 mice at different stages of
the oestrous cycle, and in ovariectomised mice administered oestradiol and
progesterone. The cytokines that were found to fluctuate over the course of the
oestrous cycle were colony-stimulating factor (CSF)1, CSF2, interferon gamma
(IFNG) and tumour necrosis factor alpha (TNFA), all of which were significantly
elevated at oestrus compared with other phases. The concentration of serum
progesterone during the oestrus phase negatively correlated with the abundance of
cytokines CSF3, IL12p40, IFNG and leukaemia inhibitory factor (LIF). In
ovariectomised mice, exogenous oestradiol administration increased mammary gland
CSF1, CSF2, IFNG and LIF, compared with ovariectomised control mice. Progesterone
administration together with oestradiol resulted in reduced CSF1, CSF3 and IFNG
compared with oestradiol administration alone. This study suggests that the
cytokine microenvironment in the mammary gland at the oestrus phase of the
ovarian cycle is relatively pro-inflammatory compared with other stages of the
cycle, and that the oestradiol-induced cytokine microenvironment is significantly
attenuated by progesterone. A continuously fluctuating cytokine microenvironment
in the mammary gland presumably regulates the phenotypes of resident leukocytes
and may affect mammary gland cancer susceptibility.
PMID- 25138708
TI - "Old" metal oxide affinity chromatography as "novel" strategy for specific
capture of cis-diol-containing compounds.
AB - The metal oxide affinity chromatography (MOAC) materials have been extensively
used for extraction of phosphate compounds in the past decade. Actually, some of
these materials also possess adsorption affinity towards cis-diol-containing
compounds, which was seldom explored in separation field so far. Here we present
the proof-of-concept study to evaluate the feasibility of expanding MOAC for
specific capture of cis-diol biomolecules. Benefitting from the high
commercialisation of the metal oxide materials, such MOAC strategy possesses
several advantages, like synthesis-free, low cost and high expandability.
Firstly, the recognition of adenosine against 2'-deoxyadenosine was performed
using zirconium oxide and cerium oxide, two typical commercial MOAC materials.
The results showed that efficient adsorption and elution could be achieved easily
by pH switching from basic to acidic. The isotherm curves demonstrated the
adsorption process fitted well with Freundlich isotherm model and was spontaneous
at room temperature (DeltaG(0)<0) with an exothermic nature (DeltaH(0)<0).
Afterwards, the highly efficient and selective enrichment of various model cis
diol biomolecules, including ribonucleosides, glycopeptides and glycoproteins,
was achieved using this MOAC strategy. Finally, the endogenous ribonucleosides
and modified ribonucleosides were successfully purified from human urine sample,
which demonstrated the potential application of MOAC materials in the enrichment
of target compounds from complex biological samples. Besides the excellent
performance of extraction for cis-diol-containing compounds, equally important is
that these materials are commercially available with low cost, which makes the
MOAC a promising strategy for the study of cis-diol biomolecules in metabolomics
and proteomics.
PMID- 25138709
TI - Sodalis glossinidius prevalence and trypanosome presence in tsetse from Luambe
National Park, Zambia.
AB - BACKGROUND: Tsetse flies are the biological vectors of African trypanosomes, the
causative agents of sleeping sickness in humans and nagana in animals. The tsetse
endosymbiont Sodalis glossinidius has been suggested to play a role in tsetse
susceptibility to infection. Here we investigate the prevalence of African
trypanosomes within tsetse from the Luambe National Park, Zambia and if there is
an association between S. glossinidius and presence of trypanosomes within the
tsetse examined. METHODS: Tsetse representing three species (Glossina
brevipalpis, Glossina morsitans morsitans and Glossina pallidipes), were sampled
from Luambe National Park, Zambia. Following DNA extraction, PCR was used to
examine the tsetse for presence of trypanosomes and the secondary endosymbiont S.
glossinidius. RESULTS: S. glossinidius infection rates varied significantly
between tsetse species, with G. brevipalpis (93.7%) showing the highest levels of
infection followed by G. m. morsitans (17.5%) and G. pallidipes (1.4%). ITS-PCR
detected a wide variety of trypanosomes within the tsetse that were analysed.
Significant differences were found in terms of trypanosome presence between the
three tsetse species. A high proportion of G. m. morsitans were shown to carry T.
brucei s.l. DNA (73.7%) and of these around 50% were positive for Trypanosoma
brucei rhodesiense. T. vivax, T. godfreyi, T. simiae, T. simiae Tsavo and T.
congolense were also detected. No association was found between the occurrence of
S. glossinidius and the presence of trypanosome DNA in any of the three tsetse
species tested. CONCLUSION: The current work shows that T. b. rhodesiense was
circulating in Luambe National Park, representing a risk for people living in the
park or surrounding area and for tourists visiting the park. The differences in
trypanosome DNA presence observed between the different tsetse species tested may
indicate host feeding preferences, as the PCR will not discriminate between a fly
with an active/resident infection compared to a refractory fly that has fed on an
infected animal. This makes it difficult to establish if S. glossinidius may play
a role in the susceptibility of tsetse flies to trypanosome infection.
PMID- 25138710
TI - IMAGING DIAGNOSIS--URINARY BLADDER DUPLICATION IN A CAT.
AB - A female kitten presented for chronic, intermittent, antibiotic-responsive
urinary incontinence and chronic kidney disease. Abdominal ultrasound identified
bilateral pelvic/ureteral dilation and three closely apposed thin-walled fluid
filled structures in the caudal abdomen, extending toward the pelvic inlet.
Excretory urography and negative contrast cystography identified contrast medium
accumulation from the dilated ureters into two tubular soft tissue masses of the
caudal abdomen, with subsequent gradual filling of a more cranially located
urinary bladder. A retrograde vaginocystourethrogram identified a normal uterus,
normal vagina, and a single urethra continuous with the cranially located urinary
bladder. Antemortem diagnosis was suspicious for bilateral ectopic ureteroceles.
Postmortem diagnosis, 35 months following initial presentation, determined the
fluid-filled masses to have abundant smooth muscle in the wall, including a
muscularis mucosa connected by a common ostium, consistent with urinary bladder
duplication. Urinary bladder duplication should be included as a differential
diagnosis in cats with these clinical and imaging characteristics. In this case,
differentiation of ectopic ureterocele from urinary bladder duplication required
histological confirmation.
PMID- 25138711
TI - exo-Brevicomin biosynthetic pathway enzymes from the Mountain Pine Beetle,
Dendroctonus ponderosae.
AB - exoBrevicomin (exo-7-ethyl-5-methyl-6,8-dioxabicyclo[3.2.1]octane) is an
important semiochemical for a number of beetle species, including the highly
destructive Mountain Pine Beetle (Dendroctonus ponderosae). It is also found in
other insects and the African elephant. Despite its significance, very little is
known about its biosynthesis. A recent microarray analysis implicated a small
cluster of three D. ponderosae genes in exo-brevicomin biosynthesis, two of which
had identifiable open reading frames (Aw et al., 2010; BMC Genomics 11:215). Here
we report further expression profiling of two genes in that cluster and
functional analysis of their recombinantly-produced enzymes. One encodes a short
chain dehydrogenase that used NAD(P)(+) as a co-factor to catalyze the oxidation
of (Z)-6-nonen-2-ol to (Z)-6-nonen-2-one. We therefore named the enzyme (Z)-6
nonen-2-ol dehydrogenase (ZnoDH). The other encodes the cytochrome P450, CYP6CR1,
which epoxidized (Z)-6-nonen-2-one to 6,7-epoxynonan-2-one with very high
specificity and substrate selectivity. Both the substrates and products of the
two enzymes are intermediates in the exo-brevicomin biosynthetic pathway. Thus,
ZnoDH and CYP6CR1 are enzymes that apparently catalyze the antepenultimate and
penultimate steps in the exo-brevicomin biosynthetic pathway, respectively.
PMID- 25138712
TI - Immunochemical quantification of cynomolgus CYP2J2, CYP4A and CYP4F enzymes in
liver and small intestine.
AB - 1. An increasing number of studies have indicated the roles of CYP4 proteins in
drug metabolism; however, CYP4 expression has not been measured in cynomolgus
monkeys, an important animal species for drug metabolism studies. 2. In this
study, cynomolgus CYP4A11, CYP4F2/3, CYP4F11 and CYP4F12, along with CYP2J2, were
immunoquantified using selective antibodies in 28 livers and 35 small intestines,
and their content was compared with CYP1A, CYP2A, CYP2B6, CYP2C9/19, CYP2D,
CYP2E1, CYP3A4 and CYP3A5, previously quantified. 3. In livers, CYP2J2, CYP4A11,
CYP4F2/3, CYP4F11 and CYP4F12, varied 1.3- to 4.3-fold, represented 11.2, 14.4,
8.0, 2.7 and 0.3% of total immunoquantified CYP1-4 proteins, respectively. 4. In
small intestines, CYP2J2, CYP4F2/3, CYP4F11 and CYP4F12, varied 2.4- to 9.7-fold,
represented 6.9, 36.4, 2.4 and 9.3% of total immunoquantified CYP1-4 proteins,
respectively, making CYP4F the most abundant P450 subfamily in small intestines.
CYP4A11 was under the detection limit in all of the samples analyzed. 5.
Significant correlations were found in liver for CYP4A11 with lauric acid 11-/12
hydroxylation and for CYP4F2/3 and CYP4F11 with astemizole hydroxylation. 6. This
study revealed the relatively abundant contents of cynomolgus CYP2J2, CYP4A11 and
CYP4Fs in liver and/or small intestine, suggesting their potential roles for the
metabolism of xenobitotics and endogenous substrates.
PMID- 25138713
TI - Electrospun honeycomb as nests for controlled osteoblast spatial organization.
AB - Honeycomb nanofibrous scaffolds were elaborated by electrospinning onto micro
patterned collectors either with poly(epsilon-caprolactone) (PCL) or poly(D, L
lactic acid) (PLA). The unimodal distribution of fiber diameters, observed for
PLA, led to relatively flat scaffolds; on the other hand, the bimodal
distribution of PCL fiber diameters significantly increased the relief of the
scaffolds' patterns due to the preferential deposition of the thick fiber
portions on the walls of the collector's patterns via preferential electrostatic
interaction. Finally, a biological evaluation demonstrated the effect of the
scaffolds' relief on the spatial organization of MG63 osteoblast-like cells.
Mimicking hemi-osteons, cell gathering was observed inside PCL honeycomb nests
with a size ranging from 80 to 360 um.
PMID- 25138715
TI - New clinical practice guidelines on the classification, evaluation and management
of childhood interstitial lung disease in infants: what do they mean?
AB - The American Thoracic Society (ATS) recently published a clinical practice
guideline regarding the classification, evaluation, and management of childhood
interstitial lung disease in infancy (chILD). As disease entities among infants
with ILD are often distinct from forms seen in older children and adults, the
guideline encourages an age-based classification system and focuses on the
diagnostic approach to neonates and infants <2 years of age. The guideline
reviews current evidence and recommendations for the evaluation, relevant genetic
studies, and management of symptomatic infants. Here, we summarize the ATS
guideline, highlight the major concepts, and discuss future strategies aimed at
addressing current gaps in knowledge.
PMID- 25138714
TI - M1 and M2 macrophages: the chicken and the egg of immunity.
AB - The purpose of this perspective is to describe a critical advance in
understanding how immune responses work. Macrophages are required for all animal
life: 'Inhibit' type macrophages in all animals (called M1) can rapidly kill
pathogens, and are thus the primary host defense, and 'Heal' type macrophages
(M2) routinely repair and maintain tissue integrity. Macrophages perform these
activities in all animals without T cells, and also in T cell-deficient
vertebrates. Although adaptive immunity can amplify macrophage polarization, the
long-held notion that macrophages need to be 'activated' or 'alternatively
activated' by T cells is incorrect; indeed, immunology has had it backward. M1/M2
type macrophages necessarily direct T cells toward Th1- or Th2-like activities,
respectively. That such macrophage-innate activities are the central directing
element in immune responses is a dramatic change in understanding how immune
systems operate. Most important, this revelation is opening up whole new
approaches to immunotherapy. For example, many modern diseases, such as cancer
and atherosclerosis, may not display 'foreign' antigens. However, there are clear
imbalances in M1/M2-type responses. Correcting such innate imbalances can result
in better health. Macrophages are the chicken and the egg of immunity.
PMID- 25138716
TI - Deep resequencing reveals allelic variation in Sesamum indicum.
AB - BACKGROUND: Characterization of genome-wide patterns of allelic variation and
linkage disequilibrium can be used to detect reliable phenotype-genotype
associations and signatures of molecular selection. However, the use of Sesamum
indicum germplasm for breeding is limited by the lack of polymorphism data.
RESULTS: Here we describe the massively parallel resequencing of 29 sesame
strains from 12 countries at a depth of >= 13-fold coverage for each of the
samples tested. We detected an average of 127,347 SNPs, 17,961 small InDels, and
9,266 structural variants per sample. The population SNP rate, population
diversity (pi) and Watterson's estimator of segregating sites (thetaw) were
estimated at 8.6 * 10-3, 2.5 * 10-3 and 3.0 * 10-3 bp-1, respectively. Of these
SNPs, 23.2% were located within coding regions. Polymorphism patterns were
nonrandom among gene families, with genes mediating interactions with the biotic
or abiotic environment exhibiting high levels of polymorphism. The linkage
disequilibrium (LD) decay distance was estimated at 150 kb, with no distinct
structure observed in the population. Phylogenetic relationships between each of
the 29 sesame strains were consistent with the hypothesis of sesame originating
on the Indian subcontinent. In addition, we proposed novel roles for adenylate
isopentenyltransferase (ITP) genes in determining the number of flowers per leaf
axil of sesame by mediating zeatin biosynthesis. CONCLUSIONS: This study
represents the first report of genome-wide patterns of genetic variation in
sesame. The high LD distance and abundant polymorphisms described here increase
our understanding of the forces shaping population-wide sequence variation in
sesame and will be a valuable resource for future gene-phenotype and genome-wide
association studies (GWAS).
PMID- 25138717
TI - Memantine reduces alcohol drinking but not relapse in alcohol-dependent rats.
AB - Alcoholism is a chronic relapsing disorder with consequences on health and that
requires more effective treatments. Among alternative therapies, the therapeutic
potential of the non-competitive N-methyl-D-aspartate receptor antagonist
memantine has been suggested. Despite promising results, its efficiency in the
treatment of alcoholism remains controversial. Currently, there is no pre
clinical data regarding its effects on the motivation for ethanol in post
dependent (PD) animals exposed to intermittent ethanol vapor, a validated model
of alcoholism. Thus, the objectives of this study were to evaluate the effects of
acute injections of memantine (0, 12.5, 25 and 50 mg/kg) on operant ethanol self
administration in non-dependent (ND) and PD rats tested either during acute
withdrawal or relapse after protracted abstinence. Our results showed that
memantine (25 mg/kg) abolished ethanol self-administration in ND rats and reduced
by half the one of PD rats during acute withdrawal. While this effect was
observed only 6 hours after treatment in ND rats, it was long lasting in PD rats
(at least 30 hours after injection). Furthermore, our results indicated that
memantine did not modify the breaking point for ethanol. This suggests that
memantine probably act by potentiating the pharmacological effect of ethanol but
not by reducing motivation for ethanol. Finally, memantine was also ineffective
in reducing relapse after protracted abstinence. Altogether, our pre-clinical
results highlighted a potential therapeutic use of memantine that may be used as
a replacement therapy drug but not as relapse-preventing drug.
PMID- 25138718
TI - Rapid evolution of adaptive niche construction in experimental microbial
populations.
AB - Many species engage in adaptive niche construction: modification of the local
environment that increases the modifying organism's competitive fitness. Adaptive
niche construction provides an alternative pathway to higher fitness, shaping the
environment rather than conforming to it. Yet, experimental evidence for the
evolutionary emergence of adaptive niche construction is lacking, leaving its
role in evolution uncertain. Here we report a direct observation of the de novo
evolution of adaptive niche construction in populations of the bacteria
Pseudomonas fluorescens. In a laboratory experiment, we allowed several bacterial
populations to adapt to a novel environment and assessed whether niche
construction evolved over time. We found that adaptive niche construction emerged
rapidly, within approximately 100 generations, and became ubiquitous after
approximately 400 generations. The large fitness effect of this niche
construction was dominated by the low fitness of evolved strains in the
ancestrally modified environment: evolved niche constructors were highly
dependent on their specific environmental modifications. Populations were
subjected to frequent resetting of environmental conditions and severe reduction
of spatial habitat structure, both of which are thought to make adaptive niche
construction difficult to evolve. Our finding that adaptive niche construction
nevertheless evolved repeatably suggests that it may play a more important role
in evolution than generally thought.
PMID- 25138719
TI - Cross-resistance and baseline susceptibility of Mediterranean strains of Bemisia
tabaci to cyantraniliprole.
AB - BACKGROUND: The whitefly Bemisia tabaci Gennadius is a severe pest in many field
and greenhouse crops worldwide and has developed resistance to insecticides from
most chemical classes. The ease with which this pest develops resistance makes it
essential to incorporate new compounds with different modes of action and no
cross-resistance with those previously used into insecticide resistance
management strategies. To that end, the systemic effect of the new diamide
cyantraniliprole was tested with multiresistant, selected and field populations
of Q-biotype B. tabaci from the Mediterranean area. RESULTS: Bioassays with
multiresistant and laboratory-selected populations indicated no cross-resistance
to cyantraniliprole in the B. tabaci strains exhibiting resistance to other
insecticides. The LC50 values for nymphs from 14 field populations varied between
0.011 and 0.116 mg L(-1), a 10.5-fold natural variability. The LC50 values for
adults from three strains ranged from 0.060 to 0.096 mg L(-1). CONCLUSION: These
baseline data will be helpful for monitoring future potential shifts in
susceptibility to cyantraniliprole in Mediterranean whitefly populations within
an IRM programme. Cyantraniliprole may play an important role in mitigating
insecticide resistance in B. tabaci because of its high efficacy and its lack of
cross-resistance to other insecticides, even in multiresistant Q-biotype
populations collected from a highly problematic insecticide resistance area.
PMID- 25138720
TI - Recanalization of chronic total occlusions of the superior mesenteric artery in
patients with chronic mesenteric ischemia: technical and clinical outcomes.
AB - PURPOSE: To evaluate the safety and outcomes of endovascular recanalization of
chronic total occlusions (CTOs) of the superior mesenteric artery (SMA) in
patients with chronic mesenteric ischemia (CMI). MATERIALS AND METHODS: A single
institution retrospective review was performed of 47 consecutive patients (18
male, 29 female) who underwent endovascular stent placement for CTOs of the SMA
between February 2006 and November 2012. All patients had symptoms of CMI.
Procedural and follow-up data were collected for assessment of technical success,
safety, and outcome. RESULTS: Technical success was achieved in 41 of 47 patients
(87%). Forty-two of the 47 procedures were performed from a femoral approach.
Fifteen patients underwent concurrent revascularization of the celiac artery. All
patients who underwent successful recanalization reported symptomatic
improvement. Kaplan-Meier analysis revealed primary freedom from symptomatic
recurrence of 95% at 12 months and 78% at 24 months. Symptomatic recurrence was
observed in seven patients, all of whom underwent successful assisted or
secondary endovascular procedures. Secondary freedom from symptomatic recurrence
rates were 100% at 12 months and 88% 24 months. There were three (7%) minor
access-related complications and no major complications. CONCLUSIONS:
Endovascular stent-assisted recanalization of chronic SMA occlusions is safe and
effective, with an acceptable rate of technical success and excellent midterm
clinical outcomes.
PMID- 25138721
TI - Detection of potentially skin sensitizing hydroperoxides of linalool in
fragranced products.
AB - On prolonged exposure to air, linalool can form sensitizing hydroperoxides.
Positive hydroperoxide patch tests in dermatitis patients have frequently been
reported, but their relevance has not been established. Owing to a lack of
analytical methods and data, it is unclear from which sources the public might be
exposed to sufficient quantities of hydroperoxides for induction of sensitization
to occur. To address this knowledge gap, we developed analytical methods and
performed stability studies for fine fragrances and deodorants/antiperspirants.
In parallel, products recalled from consumers were analysed to investigate
exposure to products used in everyday life. Liquid chromatography-mass
spectrometry with high mass resolution was found to be optimal for the selective
and sensitive detection of the organic hydroperoxide in the complex product
matrix. Linalool hydroperoxide was detected in natural linalool, but the amount
was not elevated by storage in a perfume formulation exposed to air. No
indication of hydroperoxide formation in fine fragrances was found in stability
studies. Aged fine fragrances recalled from consumers contained a geometric mean
linalool concentration of 1,888 MUg/g and, corrected for matrix effects, linalool
hydroperoxide at a concentration of around 14 MUg/g. In antiperspirants, we
detected no oxidation products. In conclusion, very low levels of linalool
hydroperoxide in fragranced products may originate from raw materials, but we
found no evidence for oxidation during storage of products. The levels detected
are orders of magnitude below the levels inducing sensitization in experimental
animals, and these results therefore do not substantiate a causal link between
potential hydroperoxide formation in cosmetics and positive results of patch
tests.
PMID- 25138722
TI - Characterizing Pluripotent Stem Cells Using the TaqMan(r) hPSC Scorecard(TM)
Panel.
AB - Rapid technological developments for the efficient generation of footprint-free
induced pluripotent stem cells (iPSC) enabled the creation of patient-specific
iPSC for downstream applications in drug discovery and regenerative medicine.
However, the large number of iPSCs, generated from diverse genetic backgrounds
using various methods and culture conditions, created a steep challenge for rapid
characterization and a demand for standardized methods. Current methods rely on a
combination of in vitro and in vivo cellular analyses based on the expression of
markers of self-renewal and the ability of the cells to differentiate into cell
types representative of the three germ layers as a confirmation of functional
pluripotency. These methods, though informative and extensively used, are not
ideal for parallel analyses of large numbers of samples and hence not amenable to
high-throughput environments. Recently, genetic and epigenetic expression
signatures were used to define and confirm cell states, thus providing a
surrogate molecular assay that can potentially replace complex in vivo cellular
assays such as teratoma formation. In this chapter, we describe a molecular assay
for rapid characterization and standardization of pluripotent stem cells. The
TaqMan((r)) hPSC ScorecardTM Panel is a comprehensive gene expression real-time
PCR assay that consists of 94 individual q-PCR assays comprised of a combination
of control, housekeeping, self-renewal, and lineage-specific genes. The resulting
expression data set is analyzed using cloud-based analysis software that compares
the expression pattern against a reference standard composed of multiple
functionally validated ESC and iPSC lines. This system was successfully used to
test several ESC and iPSC lines in their undifferentiated states to confirm their
signatures of self renewal, as well as their terminally differentiates states,
via spontaneous differentiation and directed differentiation into specific
lineages, to determine the lines' differentiation potential. This genetic
analysis tool, together with the flexibility to utilize varying sample inputs and
preparation methods, provides a rapid method to confirm functional pluripotency
of ESCs and iPSCs.
PMID- 25138723
TI - GMP-compliant human adipose tissue-derived mesenchymal stem cells for cellular
therapy.
AB - Stem cells, which can be derived from different sources, demonstrate promising
therapeutic evidences for cellular therapies. Among various types of stem cell,
mesenchymal stem cells are one of the most common stem cells that are used in
cellular therapy. Human subcutaneous adipose tissue provides an easy accessible
source of mesenchymal stem cells with some considerable advantages. Accordingly,
various preclinical and clinical investigations have shown enormous potential of
adipose-derived stromal cells in regenerative medicine. Consequently, increasing
clinical applications of these cells has elucidated the importance of safety
concerns regarding clinical transplantation. Therefore, clinical-grade
preparation of adipose-derived stromal cells in accordance with current good
manufacturing practice guidelines is an essential part of their clinical
applications to ensure the safety, quality, characteristics, and identity of cell
products. Additionally, GMP-compliant cell manufacturing involves several issues
to provide a quality assurance system during translation from the basic stem cell
sciences into clinical investigations and applications. On the other hand,
advanced cellular therapy requires extensive validation, process control, and
documentation. It also evidently elucidates the critical importance of production
methods and probable risks. Therefore, implementation of a quality management and
assurance system in accordance with GMP guidelines can greatly reduce these risks
particularly in the higher-risk category or "more than minimally manipulated"
products.
PMID- 25138724
TI - Interstitial diffusion and the relationship between compartment modelling and
multi-scale spatial-temporal modelling of (18)F-FLT tumour uptake dynamics.
AB - Tumour cell proliferation can be imaged via positron emission tomography of the
radiotracer 3'-deoxy-3'-18F-fluorothymidine (18F-FLT). Conceptually, the number
of proliferating cells might be expected to correlate more closely with the
kinetics of 18F-FLT uptake than with uptake at a fixed time. Radiotracer uptake
kinetics are standardly visualized using parametric maps of compartment model
fits to time-activity-curves (TACs) of individual voxels. However the
relationship between the underlying spatiotemporal accumulation of FLT and the
kinetics described by compartment models has not yet been explored. In this work
tumour tracer uptake is simulated using a mechanistic spatial-temporal model
based on a convection-diffusion-reaction equation solved via the finite
difference method. The model describes a chain of processes: the flow of FLT
between the spatially heterogeneous tumour vasculature and interstitium;
diffusion and convection of FLT within the interstitium; transport of FLT into
cells; and intracellular phosphorylation. Using values of model parameters
estimated from the biological literature, simulated FLT TACs are generated with
shapes and magnitudes similar to those seen clinically. Results show that the
kinetics of the spatial-temporal model can be recovered accurately by fitting a 3
tissue compartment model to FLT TACs simulated for those tumours or tumour sub
volumes that can be viewed as approximately closed, for which tracer diffusion
throughout the interstitium makes only a small fractional change to the quantity
of FLT they contain. For a single PET voxel of width 2.5-5 mm we show that this
condition is roughly equivalent to requiring that the relative difference in
tracer uptake between the voxel and its neighbours is much less than one.
PMID- 25138725
TI - The diagnosis of and treatment recommendations for anxiety disorders.
AB - BACKGROUND: Anxiety disorders (panic disorder/agoraphobia, generalized anxiety
disorder, social phobia, and specific phobias) are the most common mental
illnesses. For example, the 12-month prevalence of panic disorder/agoraphobia is
6%. METHOD: This guideline is based on controlled trials of psychotherapy and
pharmacotherapy, retrieved by a systematic search for original articles that were
published up to 1 July 2013. Experts from 20 specialty societies and other
organizations evaluated the evidence for each treatment option from all available
randomized clinical trials and from a synthesis of the recommendations of already
existing international and German guidelines. RESULTS: 403 randomized controlled
trials were evaluated. It was concluded that anxiety disorders should be treated
with psychotherapy, psychopharmacological drugs, or both. Response rates to
initial treatment vary from 45% to 65%. Cognitive behavioral therapy is supported
by higher-level evidence than any other psychotherapeutic technique.
Psychodynamic therapy is recommended as a second-line treatment. Among anxiolytic
drugs, the agents of first choice are selective serotonin reuptake inhibitors and
serotoninnorepinephrine reuptake inhibitors. The patient's preference should be
considered in the choice of treatment. Drug treatment should be continued for 6
to 12 months after remission. If psychotherapy or drug treatment is not
adequately effective, then the treatment should be switched to the other form, or
to a combination of both. CONCLUSION: The large amount of data now available from
randomized controlled trials permits the formulation of robust evidence-based
recommendations for the treatment of anxiety disorders. Future work should more
closely address the necessary duration of psychotherapy and the efficacy of
combined psychotherapy and drug treatment.
PMID- 25138728
TI - Incomplete description.
PMID- 25138729
TI - Critical additions required.
PMID- 25138727
TI - Patients with cancer of unknown primary: a retrospective analysis of 223 patients
with adenocarcinoma or undifferentiated carcinoma.
AB - BACKGROUND: Cancer of unknown primary (CUP) now accounts for 2-3% of all fatal
cases of cancer in Germany. Histologically, most of these tumors are either
adenocarcinoma or undifferentiated carcinoma. Scant data on their clinical
features and prognosis are now available, and the published survival times are
highly variable. In this article, we document and analyze our own experience with
CUP to date. METHOD: We took all 223 patients with CUP (adenocarcinoma or
undifferentiated carcinoma) whom we saw in our CUP clinic from 2006 to 2010 as an
unaltered sample for retrospective analysis of clinical data and overall
survival. We performed the analysis with Kaplan-Meier plotting, log-rank testing,
and Cox regression. RESULTS: With a median follow-up time of 32.9 months, the
median survival from the time of diagnosis was 16.5 months. Metastases were most
commonly found in the lymph nodes, followed by the liver, bones, and lungs. The
main pre-treatment prognostic variables that remained significant after
adjustment for multiple testing were the Eastern Cooperative Oncology Group
(ECOG) score for overall state of health and the number of organ systems
involved. These variables were used to construct a practice-oriented risk
stratification. CONCLUSION: In patients with adeno- or undifferentiated CUP
syndrome, the ECOG score and the number of organ systems involved are important
risk factors.
PMID- 25138726
TI - Abdominal surgery in pregnancy--an interdisciplinary challenge.
AB - BACKGROUND: Abdominal operations are performed during ca. 2% of all pregnancies.
They represent an unusual situation not only for the patient, but also for the
involved surgeons and anesthesiologists. Appendectomy, followed by
cholecystectomy are the two most common types of operation performed during
pregnancy. Special questions arise with regard to the peri- and intraoperative
management and the optimal surgical approach. METHOD: This review is based on
pertinent articles retrieved by a selective search in the PubMed database.
RESULTS: The question of laparoscopy versus laparotomy during pregnancy has been
addressed to date only in case series and a few meta-analyses. Two meta-analyses
have shown a significantly higher rate of miscarriage after laparoscopic,
compared to open, appendectomy (relative risk [RR] 1.91, 95% confidence interval
[CI] 1.31-2.77). The risk of preterm birth is also somewhat higher after
laparoscopic appendectomy according to one meta-analysis on this subject (RR
1.44, 95% CI 0.78-1.76), but significantly lower according to another meta
analysis (2.1% vs. 8.1%, p<0.0001). For cholecystectomy, laparoscopy was
associated with a lower miscarriage rate than laparotomy (1 in 89 cases, versus 2
in 69 cases), but with a somewhat higher preterm birth rate (6 in 89 cases,
versus 2 in 69 cases). Delay or non-performance of surgery in a patient with
appendicitis or cholecystitis can lead to additional hospitalizations, a higher
miscarriage rate, premature rupture of the membranes, and preterm birth.
CONCLUSION: Laparoscopy in experienced hands is safe even during pregnancy, with
the recognized advantages of minimally invasive surgery, yet it carries a higher
miscarriage rate than laparotomy, with a comparable preterm birth rate. Before
surgery, patients should be thoroughly informed about the operation they are
about to undergo and the advantages and disadvantages of the available surgical
approaches.
PMID- 25138730
TI - Drugs can only affect symptoms.
PMID- 25138731
TI - Large group of patients cannot be found.
PMID- 25138732
TI - In reply.
PMID- 25138733
TI - Mode of delivery and subsequent reproductive patterns. A national follow-up
study.
AB - OBJECTIVE: To investigate associations between mode of delivery and subsequent
reproductive outcomes. DESIGN: Cohort study. POPULATION: Women with term
singleton live births from 1987 to 2009. SETTING: Denmark, birth registration
data. METHODS: Women with a first singleton delivery after 37 weeks were followed
until the end of 2010, from a first birth to include subsequent live births. We
used Cox's proportional hazards model stratified by parity to compare the
likelihood for subsequent delivery according to mode of delivery at first and
later births, estimating maternal age effects and lag time to next delivery. MAIN
OUTCOME MEASURE: Likelihood of a subsequent live-born child by previous delivery
mode. RESULTS: We identified 642,052 women with a first delivery. Compared with
women with a non-instrumental vaginal delivery, delivering a child by elective
cesarean section implied a 23% (95% CI 0.76-0.787) decreased likelihood for
subsequent delivery. Emergency cesarean section meant 16% fewer (95% CI 0.84
0.85), and vaginal instrumental delivery 4% fewer subsequent deliveries (95% CI
0.95-0.96). Hazard ratios were largely unchanged after controlling for parity and
year of birth. Small age-trends were seen, with hazard ratios affected by
maternal age at birth. Delivery mode at first birth affected marginally the time
lag until next birth. CONCLUSIONS: Fecundity, measured as likelihood of a
successive live-born child, varied with mode of delivery at the first and also
subsequent births. A first or later delivery by cesarean section implied
decreased likelihood of subsequent delivery compared with women with a first
vaginal birth.
PMID- 25138734
TI - A novel real-time CTL assay to measure designer T-cell function against HIV
Env(+) cells.
AB - BACKGROUND: To increase the immunosurveillance in HIV infection, we used
retroviral vectors expressing CD4-chimeric antigen receptors (CARs) to
genetically modify autologous T cells and redirect CTL toward HIV. The CD4
extracellular domain targets envelope and the intracellular signaling domains
activate T cells. The maC46 fusion inhibitor binds HIV and blocks viral
replication. METHODS: We stimulated rhesus PBMCs with antibodies to CD3/CD28 and
cotransduced T cells with CD4-CAR and maC46 vectors. CD4-CAR-transduced T cells
were added to Env(+) 293T cells at E:T of 1:1. Killing of target cells was
measured as reduced impedance. RESULTS: We observed gene expression in 60-70% of
rhesus CD3(+) CD8(+) T cells with the individual vectors and in 35% of the cells
with both vectors. CD4-CAR-transduced populations specifically killed Env(+)
cells. CONCLUSIONS: In these studies, we showed that designer T cells were
redirected to kill Env(+) cells. Control of viremia without HAART would
revolutionize treatment for HIV patients.
PMID- 25138735
TI - Efficient water-splitting device based on a bismuth vanadate photoanode and thin
film silicon solar cells.
AB - A hybrid photovoltaic/photoelectrochemical (PV/PEC) water-splitting device with a
benchmark solar-to-hydrogen conversion efficiency of 5.2% under simulated air
mass (AM) 1.5 illumination is reported. This cell consists of a gradient-doped
tungsten-bismuth vanadate (W:BiVO4 ) photoanode and a thin-film silicon solar
cell. The improvement with respect to an earlier cell that also used gradient
doped W:BiVO4 has been achieved by simultaneously introducing a textured
substrate to enhance light trapping in the BiVO4 photoanode and further
optimization of the W gradient doping profile in the photoanode. Various PV cells
have been studied in combination with this BiVO4 photoanode, such as an amorphous
silicon (a-Si:H) single junction, an a-Si:H/a-Si:H double junction, and an a
Si:H/nanocrystalline silicon (nc-Si:H) micromorph junction. The highest
conversion efficiency, which is also the record efficiency for metal oxide based
water-splitting devices, is reached for a tandem system consisting of the
optimized W:BiVO4 photoanode and the micromorph (a-Si:H/nc-Si:H) cell. This
record efficiency is attributed to the increased performance of the BiVO4
photoanode, which is the limiting factor in this hybrid PEC/PV device, as well as
better spectral matching between BiVO4 and the nc-Si:H cell.
PMID- 25138736
TI - Effects of supplementation with Heracleum persicum fruit extract on serum lipids
in patients undergoing coronary angiography: a pilot trial.
AB - Heracleum persicum Desf. Ex Fischer (Apiaceae) is a native medicinal plant in the
Iranian traditional medicine and also a safe and common dietary spice. The
present pilot study aimed to investigate the impact of supplementation with H.
persicum fruits on serum lipid concentrations in a group of patients with minimal
coronary artery disease. Subjects who were diagnosed with <50% luminal narrowing
in any of the major coronary arteries in coronary angiography were recruited for
this trial and were randomized to receive either H. persicum hydroalcoholic fruit
extract (n=15; 300 mg/day) or placebo (n=12) for a period of 6 months. Serum
concentrations of total cholesterol, low-density lipoprotein cholesterol, high
density lipoprotein cholesterol, and triglycerides were measured at baseline and
at the end of study. No significant difference in concentrations of total
cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein
cholesterol was observed between H. persicum extract and placebo groups (p>0.05).
However, serum triglycerides levels were reduced after H. persicum extract
supplementation in a borderline significant manner (p=0.063). Short-term
supplementation with H. persicum fruit extract might be used as an adjunctive
treatment for patients with hypertriglyceridemia.
PMID- 25138737
TI - Alternative treatment of stereotactic cyst aspiration and radiosurgery for cystic
brain metastases.
AB - BACKGROUND: Surgical removal is the first choice of treatment for large cystic
brain metastases. However, some patients cannot undergo surgical resection due to
their general condition and/or the tumor location. AIMS: In this study, we
investigated the feasibility and safety of stereotactic cyst aspiration and gamma
knife radiosurgery (GKR) as an alternative treatment for these lesions and
followed the volumetric changes in cystic and solid portions. METHODS: Between
February 2005 and March 2012, a total of 24 patients underwent GKR after cyst
aspiration for 29 cystic metastatic brain tumors. The median age was 60 years
(range, 18-81). The number of male patients was 18 and that of female patients 6.
Most of the patients were in class II (87.5%) based on the data of the Radiation
Therapy Oncology Group using recursive partitioning analysis. We analyzed the
changes in tumor volume, the local control rate, intracranial progression-free
survival (PFS) and overall survival (OS). RESULTS: Before aspiration, the mean
total tumor volume was 32.7 cm(3) (range, 12.1-103.3) and cystic volume was 18.6
cm(3) (range, 8-72.3). The mean duration of cyst drainage was 1 day (range, 1-2).
The mean amount of aspiration was 16.8 cm(3) (range, 6-67.4). After aspiration,
the total mean volume was 12.4 cm(3) (range, 3.7-38.1) and cystic volume was 2.0
cm(3) (range, 0.1-9.5). The nature of the cyst was serous in 18, serous and
hemorrhagic in 3, and serous and necrotic in 8. The median prescription dose was
16 Gy (range, 14-20). There was no treatment-related complication. The local
control rate was 58.6% (17/29). The median survival to local recurrence was 6.0
(+/-1.42) months. During the follow-up period, an Ommaya reservoir was placed in
3 patients. Insertion of an Ommaya reservoir and whole-brain radiotherapy (WBRT)
or GKR were done in 2 patients, WBRT in 2, GKR in 1 and operation in 1. The
median intracranial PFS and OS after intracranial metastasis was 5.2 (+/-0.42)
and 6.8 (+/-0.38) months. CONCLUSIONS: Cyst aspiration and GKR were feasible and
safe but not very efficient, which could be an alternative option for large
cystic metastases in patients who could not expect longer survival time.
PMID- 25138738
TI - Atrial electromechanical delay is impaired in patients with psoriasis.
AB - OBJECTIVE: In this study, we aimed to investigate atrial electromechanical delay
(EMD) in patients with psoriasis. SUBJECTS AND METHODS: A total of 43 patients
with psoriasis (26 mild-moderate, 17 severe) and 17 healthy control subjects were
enrolled. Patients with psoriasis were divided into two groups: the mild-moderate
group and the severe group according to their psoriasis area severity index
(PASI) scores. Atrial EMD was measured from the lateral mitral annulus and called
'PA lateral', from the septal mitral annulus, called 'PA septal', and from the
right ventricle tricuspid annulus, called 'PA tricuspid'. Atrial EMD was defined
as the time interval from the onset of atrial electrical activity (P wave on
surface ECG) to the beginning of mechanical atrial contraction (late diastolic A
wave). All three groups were compared with each other, and correlation analysis
was performed to investigate the relationship between the PASI score and
interatrial EMD. RESULTS: PA lateral was significantly higher in both the mild
moderate psoriasis group and the severe psoriasis group compared to controls (69
+/- 12 and 78 +/- 13 vs. 60 +/- 6 ms; p = 0.001). Also, PA septal (63 +/- 11 vs.
53 +/- 6 ms; p = 0.005, post hoc analysis) and PA tricuspid (49 +/- 7 vs. 41 +/-
5 ms; p = 0.009, post hoc analysis) were significantly higher in the severe
psoriasis group than in the control group. Correlation analysis revealed that the
PASI score was well correlated with PA lateral (r = 0.520, p < 0.001), PA septum
(r = 0.460, p = 0.002), interatrial EMD (r = 0.371, p = 0.014) and intra-atrial
EMD (r = 0.393, p = 0.009). CONCLUSION: Atrial EMD was prolonged in patients with
psoriasis. The measurement of atrial EMD might be used to determine the risk of
development of AF in patients with psoriasis.
PMID- 25138739
TI - Prototype of biliary drug-eluting stent with photodynamic and chemotherapy using
electrospinning.
AB - BACKGROUND: The combination of biliary stent with photodynamic and chemotherapy
seemed to be a beneficial palliative treatment of unresectable
cholangiocarcinoma. However, by intravenous delivery to the target tumor the
distribution of the drug had its limitations and caused serious side effect on
non-target organs. Therefore, in this study, we are going to develop a localized
eluting stent, named PDT-chemo stent, covered with gemcitabine (GEM) and
hematoporphyrin (HP). METHODS: The prototype of PDT-chemo stent was made through
electrospinning and electrospraying dual-processes with an electrical charge to
cover the stent with a drug-storing membrane from polymer liquid. The design of
prototype used PU as the material of the backing layer, and PCL/PEG blends in
different molar ratio of 9:1 and of 1:4 were used in two drug-storing layers with
GEM and HP loaded respectively. RESULTS: The optical microscopy revealed that the
backing layer was formed in fine fibers from electrospinning, while drug-storing
layers, attributed to the droplets from electrospraying process. The covered
membrane, the morphology of which was observed by scanning electron microscopy
(SEM), covered the stent surface homogeneously without crack appearances. The GEM
had almost 100% of electrosprayed efficiency than 70% HP loaded on the covered
membrane due to the different solubility of drug in PEG/PCL blends. Drug release
study confirmed the two-phased drug release pattern by regulating in different
molar ratio of PEG/PCL blends polymer. CONCLUSIONS: The result proves that the
PDT-chemo stent is composed of a first burst-releasing phase from HP and a later
slow-releasing phase from GEM eluting. This two-phase of drug eluting stent may
provide a new prospect of localized and controlled release treatment for
cholangiocarcinoma disease.
PMID- 25138740
TI - Quercetin reduces pluripotency, migration and adhesion of human teratocarcinoma
cell line NT2/D1 by inhibiting Wnt/beta-catenin signaling.
AB - Quercetin, a bioflavonoid found in plant foods, has a wide range of therapeutic
effects. In order to examine the therapeutic potential of quercetin in
teratocarcinoma, we used the human teratocarcinoma cell line NT2/D1 as an in
vitro model. We have shown that quercetin inhibits the proliferation, adhesion
and migration of NT2/D1 cells and downregulates the expression of pluripotency
factors SOX2, Oct4 and Nanog. Our results further suggest that the anticancer
effect of quercetin against human teratocarcinoma cells is mediated by targeting
the canonical Wnt signaling pathway. Quercetin antagonized the Wnt/beta-catenin
signaling pathway in NT2/D1 cells by inhibiting beta-catenin nuclear
translocation and the consequent downregulation of beta-catenin-dependent
transcription. These data suggest that quercetin as a potent inhibitor of Wnt
signaling may be an effective therapeutic agent in cancers with aberrant
activation of the Wnt pathway.
PMID- 25138741
TI - Comprehensive three-dimensional analysis of right-sided aortic arch with multiple
vascular anomalies.
AB - BACKGROUND: Right-sided aortic arch is a rare congenital defect usually diagnosed
incidentally in adults; it is often asymptomatic unless aneurismal disease
develops. In half the cases, an aberrant left subclavian artery arises from a
Kommerell's diverticulum; in these cases, congenital heart anomaly is very rarely
present. CASE PRESENTATION: We report a case of incidentally-detected right-sided
aortic arch with multiple vascular anomalies including left subclavian artery
originating from a Kommerell's diverticulum, supra-sinus origin of coronary
arteries and coronary arteriovenous fistula. CONCLUSION: Through comprehensive 3
dimensional reconstruction of the aortic arch and surrounding structures we
defined anatomical relationships, which is useful for follow-up and treatment.
PMID- 25138742
TI - Amblyopia and the H Barry Collin research medal.
PMID- 25138743
TI - Why are we still fitting reusable soft contact lenses?
PMID- 25138744
TI - The tear ferning test: a simple clinical technique to evaluate the ocular tear
film.
AB - A healthy tear film is very important for many major functions of the ocular
surface. Dry eye disease is a significant clinical problem that needs to be
solved but the poor correlation between clinical signs and reported symptoms
makes it difficult for the clinician to apply a scientific basis to his clinical
management. The problem is compounded by the difficulties of evaluating the tear
film due to its transparency, small volume and complex composition. Practical
insight into tear film composition would be very useful to the clinician for
patient diagnosis and treatment but detailed analysis is restricted to expensive,
laboratory-based systems. There is a pressing need for a simple test. The tear
ferning test is a laboratory test but it has the potential to be applied in the
clinic setting to investigate the tear film in a simple way. Drying a small
sample of tear fluid onto a clean, glass microscope slide produces a
characteristic crystallisation pattern, described as a 'tear fern'. This test is
currently not widely used because of some limitations that need to be overcome
but several studies have demonstrated its potential. Such limitations need to be
resolved so that tear ferning could be used in the clinic setting to assess the
tear film.
PMID- 25138745
TI - Post-cataract surgery diplopia: aetiology, management and prevention.
AB - Diplopia is an infrequent but distressing adverse outcome after uncomplicated
cataract surgery. Many factors may contribute to the occurrence of this problem,
including prolonged sensory deprivation resulting in disruption of sensory
fusion, paresis of one or more extraocular muscles, myotoxic effects of local
anaesthesia, optical aberrations (for example, aniseikonia) and pre-existing
disorders (for example, thyroid orbitopathy). The purpose of this review is to
present the aetiology and clinical features of diplopia after cataract surgery
and to discuss the possible modalities for the prevention and treatment of this
frustrating complication.
PMID- 25138746
TI - Comparison of four different binocular balancing techniques.
AB - BACKGROUND: Several techniques of balancing have been proposed for the
equalisation of the accommodative state between the two eyes. This study was
designed to compare the results of different balancing techniques. METHODS: In
this study, 60 subjects participated. Refractive errors were determined using
retinoscopy and results were refined with monocular subjective refraction to
determine the ametropia with the most plus lens and this was used as the starting
point for balancing. The monocular refractive values before the balance were the
same for all balancing procedures. Four balancing techniques, three dissociated
and one associated, (alternate occlusion, prism-dissociated blur balance, prism
dissociated red-green balance and Humphriss immediate contrast method) were used
for the final refinement of findings. Results were analysed as the interocular
spherical difference (IOSD) after the completion of each balance procedure. The
interocular spherical difference was defined as the right eye sphere minus the
left eye sphere. Data were analysed in SPSS.17 software using the paired samples
t-test, the Pearson correlation, repeated measures ANOVA and 'intraclass
correlation coefficient' (ICC) tests. RESULTS: The lowest mean difference was
related to the alternate occlusion with the prism-dissociated blur balance
techniques. The lowest 95% limits of agreement were related to the prism
dissociated red-green balance with the Humphriss immediate contrast methods. The
highest correlation and intraclass correlation coefficient were related to the
prism-dissociated red-green balance with the Humphriss immediate contrast
methods. CONCLUSIONS: The four balancing methods yield very similar results. The
balance findings with red-green dissociated method and the Humphriss immediate
contrast technique can be considered interchangeable and the other pairs of
comparisons very nearly so.
PMID- 25138747
TI - Selection considerations when using a 'standard optometrist' to evaluate clinical
performance of other eye-care personnel.
AB - BACKGROUND: Selection of a standard professional is crucial for assessing the
clinical performance of other eye-care personnel. This paper describes the
selection considerations and the clinical competency assessment of two
optometrists required to select a 'standard optometrist' (SO) for evaluating the
clinical performance of vision technicians in India. METHODS: Two optometrists
were short-listed from 21 optometrists who responded to an advertisement to be
selected as a SO for the assessment of the performance of 24 vision technicians
in rural vision centres. Each candidate optometrist performed a routine eye
examination on 40 randomly selected, newly registered subjects in a tertiary
hospital clinic. Their non-cycloplegic retinoscopic findings were compared with
those of an experienced optometrist, while disease diagnoses were compared with
the findings of an ophthalmologist. RESULTS: A comparison of retinoscopic
findings showed that optometrist A produced retinoscopic values within +/-0.50 D
agreement for the spherical equivalent (SE) 100 per cent of the time, while
optometrist B obtained agreement 91.3 per cent of the time. Similarly,
optometrist A's limits of agreement (SE = -0.63 to +0.45 D) and reproducibility
limits (SE = 0.78 D) were better than those of optometrist B (SE = -0.98 to +0.70
D and SE =1.18 D, respectively). Optometrist A demonstrated 89.2 per cent
sensitivity in detecting ocular pathology compared to 76.3 per cent by
optometrist B. CONCLUSIONS: Optometrist A achieved consistent and reproducible
retinoscopic findings as well as higher sensitivity in detecting ocular pathology
and was selected as the SO for a study to assess the clinical performance of one
year trained vision technicians. The concept of a SO calibrated against an
ophthalmologist for disease detection and diagnosis and an experienced
optometrist for retinoscopy is a useful approach for the evaluation of eye-care
personnel.
PMID- 25138748
TI - Prevalence of visual problems among stroke survivors in Hong Kong Chinese.
AB - BACKGROUND: Stroke, a common cerebrovascular accident, usually results in various
extents of functional disability. Extensive studies have shown that ocular and
visual problems are common in patients with stroke. Unfortunately, current stroke
rehabilitation programs rarely address stroke-related ocular and visual problems
in Hong Kong. METHODS: To examine how visual impairment (for example,
deterioration in visual acuity and restriction in visual field) affects the
stroke population in Hong Kong, vision screening was conducted for post-stroke
patients attending in-patient and out-patient stroke clinics at two hospitals.
RESULTS: One hundred and thirteen stroke patients were recruited. The percentage
of various aspects of visual problems in Hong Kong post-stroke patients was
generally lower than that reported in Western countries; however, a high
percentage of patients had deficits in oculomotor (53.1 per cent) and vergence
functions (11.5 per cent), restrictions in binocular visual field (11.5 per cent)
and impairment in visual acuity (worse than 0.30 logMAR, 29.8 per cent).
Conversely, only a small proportion of patients noticed problems with their
vision (for example, diplopia and blurry vision) through subjective reports. This
revealed that many post-stroke patients had undetected or undiagnosed ocular and
visual problems. Appropriate referral was given to patients with visual problems
for further evaluation and treatment. CONCLUSION: Neglecting visual problems may
impose deteriorating effect on patients' stroke rehabilitation and functional
independence and lead to increased incidents of injury. To address this potential
hindrance in rehabilitation, formal screening for visual problems in stroke
patients in a rehabilitation setting is essential.
PMID- 25138749
TI - Agreement study of keratometric values measured by Biograph/LENSTAR, auto-kerato
refractometer and Pentacam: decision for IOL calculation.
AB - BACKGROUND: The aim was to determine the agreement in keratometric readings
measured with the Biograph/LENSTAR, the Pentacam and an auto-kerato-refractometer
in a 40- to 64-year-old population. METHODS: This report is part of the first
phase of the population-based Shahroud Cohort Eye Study. In virgin eyes,
agreement among keratometry readings of three devices was examined in 7,260 eyes
using the Bland-Altman method. The inter-device 95 per cent limits of agreement
(95% LoA) and 95% confidence interval for upper and lower limits of agreement
were calculated. Comparisons were made for keratometric readings of the flat and
steep meridians as maximum keratometry (max-K), minimum keratometry (min-K) and
their average (mean-K). RESULTS: Based on Biograph/LENSTAR measurements, averages
of max-K, min-K and mean-K were 44.70 +/- 1.64, 43.87 +/- 1.54 and 44.28 +/- 1.58
D, respectively. The quantile-quantile plot revealed that all three variables had
normal distributions in this population. Agreement between the Biograph/LENSTAR
and the auto-kerato-refractometer (max-K difference: -0.03 D, 95% LoA: -0.81 to
0.75; min-K difference: -0.08 D, 95% LoA: -0.85 to 0.68) was better than the
agreement between the Biograph/LENSTAR and the Pentacam (max-K difference: 0.50
D, 95% LoA: -3.24 to 4.25; min-K difference: 0.59 D, 95% LoA: -3.00 to 4.17). The
agreement between the Pentacam and the auto-kerato-refractometer (max-K
difference: 0.54 D, 95% LoA: -3.16 to 4.24; min-K difference: 0.66 D, 95% LoA:
0.77 to 0.53) was worse than the other two pairs. CONCLUSION: These three devices
are not interchangeable in terms of keratometry for calculation of the
intraocular lens power. Agreement between the Biograph/LENSTAR and the auto
kerato-refractometer can be increased with regression models but this is not true
in case of Biograph/LENSTAR and Pentacam.
PMID- 25138750
TI - Professor Robert F Hess DSc PhD MSc DipOptom: awarded the H Barry Collin Research
Medal for 2013.
PMID- 25138751
TI - Acute macular neuroretinopathy: the evolution of the disease through the use of
newer diagnostic modalities.
PMID- 25138752
TI - Combined hamartoma of the retina and retinal pigment epithelium with hypo
autofluorescence and cystic degeneration at the macula.
PMID- 25138755
TI - Interventional magnetic resonance imaging-guided cell transplantation into the
brain with radially branched deployment.
AB - Intracerebral cell transplantation is being pursued as a treatment for many
neurological diseases, and effective cell delivery is critical for clinical
success. To facilitate intracerebral cell transplantation at the scale and
complexity of the human brain, we developed a platform technology that enables
radially branched deployment (RBD) of cells to multiple target locations at
variable radial distances and depths along the initial brain penetration tract
with real-time interventional magnetic resonance image (iMRI) guidance. iMRI
guided RBD functioned as an "add-on" to standard neurosurgical and imaging
workflows, and procedures were performed in a commonly available clinical MRI
scanner. Multiple deposits of super paramagnetic iron oxide beads were safely
delivered to the striatum of live swine, and distribution to the entire putamen
was achieved via a single cannula insertion in human cadaveric heads. Human
embryonic stem cell-derived dopaminergic neurons were biocompatible with the iMRI
guided RBD platform and successfully delivered with iMRI guidance into the swine
striatum. Thus, iMRI-guided RBD overcomes some of the technical limitations
inherent to the use of straight cannulas and standard stereotactic targeting.
This platform technology could have a major impact on the clinical translation of
a wide range of cell therapeutics for the treatment of many neurological
diseases.
PMID- 25138756
TI - Sequential therapy with ranibizumab and dexamethasone intravitreal implant is
better than dexamethasone monotherapy for macular oedema due to retinal vein
occlusion.
AB - PURPOSE: To evaluate the efficacy and safety of sequential therapy with
ranibizumab followed by dexamethasone intravitreal implant compared with
dexamethasone monotherapy for macular oedema (MO) secondary to retinal vein
occlusion (RVO). METHODS: In this retrospective interventional study, the medical
records of subjects with MO due to RVO who received either ranibizumab followed
by dexamethasone intravitreal implant (Group 1) or dexamethasone-implant
monotherapy (Group 2) were included. Primary outcome was the proportion of
subjects who exhibited best-corrected visual acuity (VA) gain and resolution of
MO within 6 months. RESULTS: Thirty-three eyes were included (17 in Group 1, 16
in Group 2). More subjects in Group 1 exhibited a VA gain of at least 0.5 (LogMAR
units hereafter) than Group 2 (29% vs 0%, p=0.044). The speed of VA gain was
greater in Group 1 (1.4+/-0.8 months vs 2.7+/-1.4 months, p=0.020). MO was
controlled in more subjects in Group 1 at all measured time intervals, and this
difference was statistically significant at 3 months and 4 months. Subjects with
branch RVO experienced VA gain more rapidly if they were from Group 1 (p=0.023).
CONCLUSIONS: Sequential therapy was found to be more effective than dexamethasone
monotherapy in treating MO due to RVO.
PMID- 25138757
TI - A comparison of methods used to evaluate mobility performance in the visually
impaired.
AB - PURPOSE: To compare three different approaches to measuring mobility performance
when evaluating the visually impaired. METHODS: 488 participants, including 192
glaucoma, 112 age-related macular degeneration, 91 diabetic retinopathy and 93
healthy volunteers, completed the Assessment of Disability Related to Vision
(ADREV) mobility course. The performance of participants on the mobility course
was evaluated by noting errors made and time required for completion. Errors
noted and time taken were compared using multivariate logistic regression to
determine which measurement better differentiated patients with visual disease
from healthy volunteers. Multivariate logistic regression was also used to
evaluate the combined metric of ADREV errors divided by time to determine its
ability to discriminate participants with visual disease from healthy volunteers.
RESULTS: Errors noted and time taken while ambulating through the standardised
mobility course shared a weak but statistically significant association
(Pearson's r=0.36, p<0.05). After controlling for demographic and medical
comorbidities, logistic regression analysis revealed that errors noted were
better at discriminating individuals with visual disease from healthy volunteers
(OR 2.8-4.9, 95% CI 1.5 to 10.3) compared with the time taken for mobility course
completion (OR 1.1, 95% CI 1.0 to 1.2). These findings were consistent across all
comparisons between healthy volunteers and participants with each type of visual
impairment. Finally, the combined metric of ADREV errors divided by time was far
more predictive of visual disease compared with either time taken or errors noted
during mobility testing (OR 11.0-17.7, 95% CI 3.6 to 77.1). CONCLUSIONS: A
validated scoring system based on errors is more effective when assessing visual
disability during mobility testing than recording the time taken for course
completion. The combined metric of ADREV errors noted divided by time taken was
most predictive of all the methods used to evaluate visual disability during
mobility testing.
PMID- 25138758
TI - Comparative role of 20% cord blood serum and 20% autologous serum in dry eye
associated with Hansen's disease: a tear proteomic study.
AB - BACKGROUND: To compare the role of topically applied serum therapy with
preservative-free artificial tear (AT) drops in patients with moderate to severe
dry eye in Hansen's disease along with change in tear protein profile. METHODS:
144 consecutive patients were randomly divided into three groups. After a
baseline examination of clinical parameters, each of the patients received
designated modality of topical therapy six times a day for 6 weeks. Post
treatment documentation of clinical parameters was done at 6 weeks, and then at
12 weeks after discontinuation of topical therapy. Analysis of three tear
proteins using gel electrophoresis (sodium dodecyl sulfate polyacrylamide gel
electrophoresis) was done at baseline, at the first and second post-treatment
visits. RESULTS: In the cord blood serum (CBS) group, except for McMonnies score
and staining score, all other clinical parameters showed continued improvement in
the first and second post-treatment analyses. In the autologous serum (ALS)
group, all the clinical parameters except Schirmer's I showed significant
improvement in the first post-treatment analysis .This was sustained at a
significant level in the second analysis except for tear film break-up time
(TBUT) and conjunctival impression cytology grading. In the AT group, all the
parameters improved at a non-significant level except for TBUT in the first
analysis. In the next analysis, apart from McMonnies score and TBUT, other
clinical parameters did not improve. In the ALS and CBS groups, tear lysozyme,
lactoferrin levels improved in both post-treatment measurements (statistically
insignificant).Total tear protein continued to increase at statistically
significant levels in the first and second post-treatment analyses in the CBS
group and at a statistically insignificant level in the ALS group. In the AT
group, the three tear proteins continued to decrease in both the analyses.
CONCLUSIONS: In moderate to severe dry eye in Hansen's disease, serum therapy in
comparison with AT drops, improves clinical parameters and causes betterment in
tear protein profile. TRIAL REGISTRATION NUMBER: CTRI/2013/07/003802.
PMID- 25138759
TI - Cystoid macular oedema following Descemet membrane endothelial keratoplasty.
AB - BACKGROUND: To determine the incidence and potential risk factors of cystoid
macular oedema (CMO) following Descemet membrane endothelial keratoplasty (DMEK)
with or without simultaneous cataract surgery. METHODS: In this study, 155 eyes
of 88 patients suffering from Fuchs endothelial dystrophy (81%), bullous
keratopathy (17.6%) or other corneal diseases (1.4%) underwent DMEK. 52% were
pseudophacic (DMEK) and 48% received simultaneous cataract surgery (DMEK combined
with cataract surgery (Triple-DMEK)) at the Eye Center at Albert Ludwigs
University of Freiburg between May 2011 and June 2013. Spectral-domain optical
coherence tomography (SD-OCT) was performed 6 weeks, 3 months and 6 months
following (Triple-)DMEK and in unscheduled visits due to limited or decreased
visual acuity. The medical records were reviewed for pre-existing comorbidities
limiting visual acuity. Patients with a history of macular oedema were excluded.
We estimated the incidence of CMO using the Kaplan-Meier method. Potential risk
factors for CMO were analysed with a Cox regression analysis and Pearson's
correlation. The Cox model included the following variables: patient age and
axial length, simultaneous cataract surgery, rate of rebubbling, donor age and
donor endothelial cell density. RESULTS: 13% of all eyes developed a single
episode of CMO at the end of the follow-up. After 6 months, 13.3% of eyes
following Triple-DMEK and 12.5% of eyes following DMEK showed CMO. There was a
statistically significant correlation between CMO development and best spectacle
corrected visual acuity. Long axial length had a protective effect on CMO
development (HR=0.3; p=0.03). Under medical therapy, central foveal thickness
decreased in all patients. CMO did not have a relevant effect on long-term visual
acuity. CONCLUSIONS: CMO is a frequent complication following DMEK in phacic and
pseudophacic eyes. The prognosis is excellent given medical treatment. We
recommend regular SD-OCT monitoring during the first 6 months following DMEK.
PMID- 25138760
TI - Inhibition by rebamipide of cytokine-induced or lipopolysaccharide-induced
chemokine synthesis in human corneal fibroblasts.
AB - BACKGROUND/AIMS: The dry-eye drug rebamipide has mucin secretagogue activity in
and anti-inflammatory effects on corneal epithelial cells. Corneal stromal
fibroblasts (transdifferentiated keratocytes) function as immune modulators in
the pathogenesis of chronic ocular allergic inflammation and in innate immune
responses at the ocular surface. The possible anti-inflammatory effects of
rebamipide on human corneal stromal fibroblasts were examined. METHODS: Serum
deprived cells were incubated for 1 h with rebamipide and then for various times
in the additional absence or presence of cytokines or bacterial
lipopolysaccharide (LPS). The release of chemokines into culture supernatants was
determined with ELISAs. The intracellular abundance of chemokine mRNAs was
quantitated by reverse transcription and real-time PCR analysis. Degradation of
the nuclear factor kappaB (NFkappaB) inhibitor IkappaBalpha was detected by
immunoblot analysis. RESULTS: Rebamipide suppressed the release of interleukin
(IL)-8 and the upregulation of IL-8 mRNA induced by tumour necrosis factor alpha
(TNF-alpha) or LPS in corneal fibroblasts. It also inhibited eotaxin-1 (CCL-11)
expression at the protein and mRNA levels induced by the combination of TNF-alpha
and IL-4. In addition, rebamipide attenuated the degradation of IkappaBalpha
induced by TNF-alpha or LPS. CONCLUSIONS: Rebamipide inhibited the synthesis of
chemokines by corneal fibroblasts in association with suppression of NFkappaB
signalling. Rebamipide may therefore prove effective for the treatment of corneal
stromal inflammation associated with allergy or bacterial infection.
PMID- 25138761
TI - Accelerated versus standard corneal collagen crosslinking combined with same day
phototherapeutic keratectomy and single intrastromal ring segment implantation
for keratoconus.
AB - AIM: To compare the results of same day transepithelial phototherapeutic
keratectomy (t-PTK) and single inferior intracorneal ring segment (ICRS) combined
with standard versus accelerated corneal collagen crosslinking (CXL) for
keratoconus. METHODS: All consecutive progressive keratoconus eyes that underwent
standard or accelerated CXL treatment preceded by same day t-PTK and placement of
a single inferior ICRS and had 6 and 12 months of follow-up were reviewed
retrospectively. Eyes were classified into two groups, the 'standard' and the
'accelerated' group, accordingly. Visual, refractive and topographic data prior
to surgery and at 6 and 12 months post-treatment were analysed. RESULTS: Sixteen
eyes were included in each of the standard and the accelerated groups. Mean
patient age was 27.5+/-8.5 years and 30.5+/-10.7 years (p=0.38) in the standard
and accelerated groups, respectively. There was a significant improvement in
uncorrected distance visual acuity, refractive cylinder and all examined corneal
parameters in both groups 12 months postsurgery. The corrected distance visual
acuity and manifest refraction spherical equivalent showed a significant
improvement after 12 months of follow-up only in the accelerated group. However,
mean changes in all evaluated parameters did not differ significantly between the
two groups. CONCLUSIONS: A combined treatment of accelerated CXL preceded by same
day t-PTK and single ICRS is as effective as the combined treatment using
standard CXL for visual rehabilitation in progressive keratoconus.
PMID- 25138762
TI - In vivo confocal microscopic characterisation of the cornea in chronic graft
versus-host disease related severe dry eye disease.
AB - AIMS: To first describe in vivo confocal microscopic (IVCM) corneal findings in
severe dry eye syndrome due to ocular chronic graft versus host disease (cGvHD)
after allogeneic stem cell transplantation. METHODS: IVCM of the central cornea
was performed in 12 prospectively recruited patients with severe ocular cGvHD
associated dry eye syndrome and in six control patients with haematological
malignancies without cGvHD. Within each examined corneal layer, at least three
non-overlapping areas were selected for representative analysis. RESULTS: The
number of sub basal nerve branches was markedly reduced in patients with cGvHD.
Sub basal nerve morphology was characterised by increased tortuosity and reduced
reflectivity. Accumulation of hyper-reflective extracellular matrix,
significantly increased haze and increased keratocyte density were found in the
anterior stroma of the study group. CONCLUSIONS: IVCM findings of the cornea in
patients with severe ocular cGvHD include a rarefaction of the sub basal corneal
nerve plexus and dense accumulation of hyper-reflective extracellular matrix in
the anterior stroma.
PMID- 25138764
TI - Two novel mutations including a large deletion of the SLC4A11 gene causing
autosomal recessive hereditary endothelial dystrophy.
PMID- 25138763
TI - Infectious involvement in a tertiary center pediatric uveitis cohort.
AB - BACKGROUND/AIMS: Studies of uveitis in children have focused primarily on non
infectious causes. To date, no systematic study of infectious uveitis in children
has been conducted. We investigate the prevalence of infectious causes of uveitis
in children and explore the diagnostic value of analysing aqueous humour.
METHODS: Retrospective cohort study in a tertiary referral centre for paediatric
uveitis. Medical records of 345 children with uveitis presenting from 1995
through 2010 were reviewed for infectious causes (by serology and aqueous humour
analysis). RESULTS: A diagnosis of infectious uveitis was established in 60/345
(17%) children. The most prevalent pathogen was Toxoplasma gondii (36/60; 60%),
followed by viral infections (18/60; 30%). The most prevalent viral pathogen was
varicella-zoster virus (VZV), representing 7/18 (39%) children. Viral causes were
less often bilateral than other infectious causes (p=0.04). Specific IgG serum
levels determined in 42/60 (70%) patients, were positive in 41/42 (98%). Aqueous
humour was analysed for 24/60 (40%) patients and was positive in 18/24 (75%).
CONCLUSIONS: An infectious cause of uveitis was identified in 17% of children
with uveitis. T gondii and VZV were the most prevalent pathogens. We recommend
analysing the aqueous humour of every child with vision-threatening uveitis of
undetermined origin.
PMID- 25138765
TI - Oral azithromycin versus doxycycline in meibomian gland dysfunction: a randomised
double-masked open-label clinical trial.
AB - BACKGROUND/AIMS: To assess the efficacy and safety of oral azithromycin compared
with oral doxycycline in patients with meibomian gland dysfunction (MGD) who had
failed to respond to prior conservative management. METHODS: 110 patients (>12
years old) with MGD were randomly assigned to receive either oral 5-day
azithromycin (500 mg on day 1 and then 250 mg/day) or 1-month doxycycline (200
mg/day). They also continued eyelid warming/cleaning and artificial tears. A
score comprising five symptoms and seven signs (primary outcome) was recorded
prior to treatment and at 1 week, and 1 and 2 months after treatment. Total score
was the sum of both scores at each follow-up. Side effects were recorded and
overall clinical improvement was categorised as excellent, good, fair or poor
based on the percentage of change in the total score. RESULTS: Symptoms and signs
improved significantly in both groups (p=0.001). While improvement of symptoms
was not different between the groups, bulbar conjunctival redness (p=0.004) and
ocular surface staining (p=0.01) were significantly better in the azithromycin
group. The azithromycin group showed a significantly better overall clinical
response (p=0.01). Mild gastrointestinal side effects were not significantly
different between the groups except for the second visit, when the doxycycline
group had significantly more side effects (p=0.002). CONCLUSIONS: Although both
oral azithromycin and doxycycline improved the symptoms of MGD, 5-day oral
azithromycin is recommended for its better effect on improving the signs, better
overall clinical response and shorter duration of treatment. TRIAL REGISTRATION
NUMBER: NCT01783860.
PMID- 25138766
TI - Transpalpebral proton beam radiotherapy of choroidal melanoma.
AB - BACKGROUND: Collateral damage to upper eyelid margin during proton beam
radiotherapy (PBR) for choroidal melanoma may cause squamous metaplasia of the
tarsal conjunctiva with keratinisation, corneal irritation, discomfort and,
rarely, corneal perforation. We evaluated transpalpebral PBR as a means of
avoiding collateral damage to the upper eyelid margin without increasing the risk
of failure of local tumour control. METHODS: Retrospective study of consecutive
patients who underwent PBR for choroidal melanoma between 1992 and 2007 at the
Royal Liverpool University Hospital and the Douglas Cyclotron at Clatterbridge
Cancer Centre, UK. RESULTS: Sixty-three patients were included in this study.
Mean basal tumour diameter and tumour thickness were 11.8 mm and 3.6 mm,
respectively. PBR mean beam range and modulation were 26.5 mm and 16.9 mm
respectively. The eyelid margin was included in the radiation field in 15 (24%)
eyes. The median follow-up was 2.5 years. Local tumour recurrence developed in 2
(3.2%) patients. In these two cases that developed tumour recurrence the
transpalpebral treatment did not involve the eyelid margin. Six (9.5%) patients
died of metastatic disease. No eyelid or ocular surface problems developed in any
of the 48 patients who were treated without eyelid rim involvement, while 7 of
the 15 patients with unavoidable irradiation of the eyelid rim developed some
degree of madarosis. These seven patients all received more than 26.55 proton Gy
to the eyelid margin. Symptoms, such as grittiness occurred in 12% of 48 patients
without eyelid margin irradiation as compared with 53% of 15 patients whose lid
margin was irradiated. CONCLUSIONS: Transpalpebral PBR of choroidal melanoma
avoids eyelid and ocular surface complications without increasing failure of
local tumour control.
PMID- 25138767
TI - Severity of acute ocular involvement is independently associated with time to
resolution of ocular disease in toxic epidermal necrolysis patients.
AB - PURPOSE: Toxic epidermal necrolysis (TEN) is a severe, life-threatening
mucocutaneous disorder that frequently involves the ocular surface. This study
aims to investigate the natural history and resolution of acute ocular
involvement in patients with TEN admitted to the intensive care unit (ICU).
METHODS: Case notes of patients admitted to ICU with TEN at a tertiary referral
centre in a 9-year period were retrospectively reviewed. Patients'
characteristics, severity of ocular involvement, SCORTEN systemic severity score
and treatment were correlated with resolution of ocular involvement and time to
resolution. RESULTS: Nine out of 10 (90%) patients had ocular involvement with 4
graded as mild, 2 as moderate and 3 as severe. All had bilateral ocular disease.
The median length of hospital stay was 28 days and the median time to resolution
of ocular involvement was 19 days. Four out of 9 (44%) patients still had active
ocular disease at the time of discharge. Only older age (p=0.032) and a milder
grade of ocular disease (p=0.001) were significantly associated with resolution
of ocular disease. In a multivariable Cox-regression model, only a milder grade
of ocular disease remained independently associated with time to resolution of
ocular disease (p=0.006). CONCLUSIONS: Grading of acute ocular disease severity
does not reflect systemic disease severity and is significantly associated with
resolution and time to resolution of ocular involvement in TEN. The high rate of
ocular involvement in patients with TEN and relatively large proportion of
patients with active disease on discharge reiterates the need for constant
ophthalmological monitoring of these patients.
PMID- 25138768
TI - Re: Ang et al: Descemet's stripping automated endothelial keratoplasty with
anterior chamber intraocular lenses: complications and 3-year outcomes.
PMID- 25138770
TI - Rationale and design of the Henry Ford Exercise Testing Project (the FIT
project).
AB - Although physical fitness is a powerful prognostic marker in clinical medicine,
most cardiovascular population-based studies do not have a direct measurement of
cardiorespiratory fitness. In line with the call from the National Heart Lung and
Blood Institute for innovative, low-cost, epidemiologic studies leveraging
electronic medical record (EMR) data, we describe the rationale and design of the
Henry Ford ExercIse Testing Project (The FIT Project). The FIT Project is unique
in its combined use of directly measured clinical exercise data retrospective
collection of medical history and medication treatment data at the time of the
stress test, retrospective supplementation of supporting clinical data using the
EMR and administrative databases and epidemiologic follow-up for cardiovascular
events and total mortality via linkage with claims files and the death registry.
The FIT Project population consists of 69 885 consecutive physician-referred
patients (mean age, 54 +/- 10 years; 54% males) who underwent Bruce protocol
treadmill stress testing at Henry Ford Affiliated Hospitals between 1991 and
2009. Patients were followed for the primary outcomes of death, myocardial
infarction, and need for coronary revascularization. The median estimated peak
metabolic equivalent (MET) level was 10, with 17% of the patients having a
severely reduced fitness level (METs < 6). At the end of the follow-up duration,
15.9%, 5.6%, and 6.7% of the patients suffered all-cause mortality, myocardial
infarction, or revascularization procedures, respectively. The FIT Project is the
largest study of physical fitness to date. With its use of modern electronic
clinical epidemiologic techniques, it is poised to answer many clinically
relevant questions related to exercise capacity and prognosis.
PMID- 25138771
TI - Fabrication of collagen scaffolds impregnated with sago starch capped silver
nanoparticles suitable for biomedical applications and their physicochemical
studies.
AB - The present investigation attempts at fabricating collagen-based scaffolds
impregnated with sago starch capped silver nanoparticles (AgNPs), useful for
biomedical applications, and aims at studying their physicochemical aspects.
AgNPs synthesized through a chemical reduction method, capped using different
concentrations of sago starch, are incorporated into collagen derived from fish
scales, and lyophilized to form scaffolds. FT-IR spectra confirm and validate the
interaction of sago starch capped AgNPs with collagen in the scaffolds. TGA and
DSC results indicate enhanced thermal stability of collagen scaffolds impregnated
with sago capped AgNPs compared to collagen alone. All the collagen scaffolds
containing sago starch capped AgNPs show high tensile strength values for their
use as wound dressing materials. Moreover, lower minimum inhibitory concentration
values are obtained for the above capped AgNP collagen scaffolds, which indicate
higher antibacterial activities compared to uncapped AgNPs tested against both
gram positive and negative bacterial strains. The novelty is that the developed
scaffolds are biodegradable and in vitro studies reveal them as biocompatible and
suitable for tissue regeneration applications.
PMID- 25138772
TI - Lactose-functionalized dendrimers arbitrate the interaction of galectin-3/MUC1
mediated cancer cellular aggregation.
AB - By using lactose-functionalized poly(amidoamine) dendrimers as a tunable
multivalent platform, we studied cancer cell aggregation in three different cell
lines (A549, DU-145, and HT-1080) with galectin-3. We found that small lactose
functionalized G(2)-dendrimer 1 inhibited galectin-3-induced aggregation of the
cancer cells. In contrast, dendrimer 4 (a larger, generation 6 dendrimer with 100
carbohydrate end groups) caused cancer cells to aggregate through a galectin-3
pathway. This study indicates that inhibition of cellular aggregation occurred
because 1 provided competitive binding sites for galectin-3 (compared to its
putative cancer cell ligand, TF-antigen on MUC1). Dendrimer 4, in contrast,
provided an excess of ligands for galectin-3 binding; this caused crosslinking
and aggregation of cells to be increased.
PMID- 25138773
TI - Potential application of aqueous two-phase systems and three-phase partitioning
for the recovery of superoxide dismutase from a clarified homogenate of
Kluyveromyces marxianus.
AB - Superoxide dismutase (SOD; EC 1.15.1.1) is an antioxidant enzyme that represents
the primary cellular defense against superoxide radicals and has interesting
applications in the medical and cosmetic industries. In the present work, the
partition behavior of SOD in aqueous two-phase systems (ATPS) (using a standard
solution and a complex extract from Kluyveromyces marxianus as sample) was
characterized on different types of ATPS (polymer-polymer, polymer-salt, alcohol
salt, and ionic liquid (IL)-salt). The systems composed of PEG 3350-potassium
phosphate, 45% TLL, 0.5 M NaCl (315 U/mg, 87% recovery, and 15.1-fold
purification) and t-butanol-20% ammonium sulfate (205.8 U/mg, 80% recovery and
9.8-fold purification), coupled with a subsequent 100 kDa ultrafiltration stage,
allowed the design of a prototype process for the recovery and partial
purification of the product of interest. The findings reported herein demonstrate
the potential of PEG-salt ATPS for the potential recovery of SOD.
PMID- 25138775
TI - A study of structure and properties of molecularly thin methanol film using the
modified surface forces apparatus.
AB - A novel approach for studying the adsorption and evaporation processes of
molecularly thin methanol film by the modified surface forces apparatus (M-SFA)
is reported. This method can be used precisely to measure the thickness,
morphology, and mechanical properties of the film confined between two mica
surfaces in a real-time manner at gas atmosphere. By observing the adsorption and
evaporation processes of the methanol molecule, it is found that the first
adsorbed layer of the methanol film on the mica surface behaves as a solid-like
structure. The thickness of this layer is measured to be about 3.2 A,
approximately equal to the diameter of a methanol molecule. Besides, this first
adsorbed layer can carry normalized loads of more than 5.6 atm due to the
carrying capacity conserved by the bond of mica-OH. The outer layers of the
methanol film are further adsorbed with the increase of the exposure time, which
are liquid-like and can be easily eliminated out from the substrate. The present
study suggests that the interacting mode between hydroxy and mica is of great
potential in material science and biomedical systems.
PMID- 25138774
TI - TGR5: pathogenetic role and/or therapeutic target in fibrosing cholangitis?
AB - Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease affecting
the intrahepatic and extrahepatic biliary tree leading to bile duct strictures,
progressive cholestasis, and development of liver fibrosis and cirrhosis. The
pathogenesis of PSC is still elusive; however, both an immune-mediated injury of
the bile ducts as well as increased recruitment of intestinal-primed T
lymphocytes to the biliary tracts seem to contribute to disease development and
progression. TGR5 (Gpbar-1) is a G-protein-coupled receptor responsive to bile
acids, which is expressed in cholangiocytes, intestinal epithelial cells, and
macrophages of the liver and intestine as well as in CD14-positive monocytes of
the peripheral blood. Activation of TGR5 in biliary epithelial cells promotes
chloride and bicarbonate secretion, triggers cell proliferation, and prevents
apoptotic cell death. In immune cells, stimulation of TGR5 inhibits cytokine
expression and secretion, thus reducing systemic as well as hepatic and
intestinal inflammation. The expression pattern of TGR5 in the liver and
intestine as well as the potential protective functions of TGR5 suggest a role
for this receptor in the pathogenesis of PSC. While mutations in the coding
region of the TGR5 gene are too rare to contribute to overall disease
susceptibility, the expression and localization of the receptor have not been
studied in PSC livers. Pharmacological activation of TGR5 in mice promotes
protective mechanisms in biliary epithelial cells and reduces hepatic and
systemic inflammation; however, it also provokes pruritus. Further studies are
needed to predict the potential benefits as well as side effects of TGR5 agonist
treatment in PSC patients.
PMID- 25138776
TI - Shifting focus of medical physics education during residency training.
PMID- 25138777
TI - Biological monitoring of particulate matter accumulated in the lungs of urban
asthmatic children in the Tel-Aviv area.
AB - PURPOSE: Lung inflammation from exposure to airborne particulate matter (PM) may
be responsible for morbidity in asthma, but several studies using environmental
monitoring data showed inconsistent results. Thus, the aim of this study was to
evaluate the capability of induced sputum (IS) technology in order to
biologically monitor PM in the lungs of urban asthmatic children. METHODS: We
collected clinical, demographic, biological and environmental monitoring data on
136 children referred for asthma evaluations. The study participants were divided
into two groups according to IS eosinophil counts of <3% (non-eosinophilic
inflammation, n = 52) and >=3% (eosinophilic inflammation, n = 84). RESULTS: The
eosinophilic group displays significantly higher levels of fractional exhaled
nitric oxide than the non-eosinophilic one (58.8 +/- 47.5 vs 28.9 +/- 34.2 ppm, p
= 0.007). Particles (0-2.5 and 0-5 um) comprised a strong risk factor for
eosinophilic inflammation in IS (>=3%). Children with >80% of particles (0-2.5
um) out of the total PM accumulated in the airways displayed the highest OR 10.7
(CI 2.052-56.4 p = 0.005) for an existing eosinophilic inflammation. Heme
oxygenase-1 (HO-1) enzyme levels in IS positively correlated with % eosinophils
and with particles in IS ranging between 2 and 3 MUm. The level of HO-1 enzyme
activity and FEV1/FVC in children with <3% eosinophils, but not >=3%, was
positively and significantly correlated, showing a protective effect of HO-1.
CONCLUSION: Accumulation of PM involves oxidative stress pathways and is a risk
factor for developing eosinophilic inflammation in asthmatic children. IS can
biologically monitor this process.
PMID- 25138778
TI - Preoperative C-reactive protein in the serum: a prognostic biomarker for upper
urinary tract urothelial carcinoma treated with radical nephroureterectomy.
AB - OBJECTIVE: To investigate the impact of preoperative serum C-reactive protein
(CRP) on clinicopathological features and prognosis in patients with upper tract
urothelial cancer (UTUC) after radical nephroureterectomy (RNU). PATIENTS AND
METHODS: Data of 265 patients from three German centers who underwent RNU for
UTUC without neoadjuvant chemotherapy between 1990 and 2012 were evaluated. Mean
follow-up was 37 months (interquartile range 9-48). CRP was analyzed as a
categorical and continuous variable for the prediction of recurrence-free
survival (RFS), disease-specific survival (DSS) and all-cause survival (ACS)
using uni- and multivariate Cox regression analyses. RESULTS: The optimal cutoff
for CRP was calculated by the Youden index at 0.90 mg/dl. Elevated CRP was
significantly associated with pT3/4 and pN+ in a preoperative model including
age, gender, tumor multifocality, tumor localization and the Eastern Cooperative
Oncology Group Performance Status. In a multivariable Cox regression model
adjusted for features significant in univariable analysis, categorized and
continuous CRP levels were both independent predictors for RFS [hazard ratio (HR)
1.18, p = 0.050; HR 1.03, p = 0.012] and DSS (HR 1.61, p = 0.026; HR 1.06, p =
0.001). Continuous CRP was an independent predictor for ACS (HR 1.05, p = 0.036).
CONCLUSIONS: Elevated preoperative CRP is significantly associated with
aggressive tumor biology and an independent predictor for poor survival after
RNU. Preoperative serum CRP represents an easily obtainable and cost-effective
marker in UTUC and may help in counseling patients with regard to operative
management and/or adjuvant or neoadjuvant therapies.
PMID- 25138780
TI - Progress towards bioorthogonal catalysis with organometallic compounds.
AB - The catalysis of bioorthogonal transformations inside living organisms is a
formidable challenge--yet bears great potential for future applications in
chemical biology and medicinal chemistry. We herein disclose highly active
organometallic ruthenium complexes for bioorthogonal catalysis under biologically
relevant conditions and inside living cells. The catalysts uncage allyl carbamate
protected amines with unprecedented high turnover numbers of up to 270 cycles in
the presence of water, air, and millimolar concentrations of thiols. By live-cell
imaging of HeLa cells and with the aid of a caged fluorescent probe we could
reveal a rapid development of intense fluorescence within the cellular cytoplasm
and therefore support the proposed bioorthogonality of the catalysts. In
addition, to illustrate the manifold applications of bioorthogonal catalysis, we
developed a method for catalytic in-cell activation of a caged anticancer drug,
which efficiently induced apoptosis in HeLa cells.
PMID- 25138781
TI - Solitary red-purple plaque on the chest of a 7-year-old boy: a quiz. Microvenular
haemangioma.
PMID- 25138782
TI - Governance practices and performance in US academic medical centers.
AB - Recognition of the complex nature of modern health care delivery has led to
interest in investigating the ways in which various factors, including governance
structures and practices, influence health care quality. In this study, the chief
executive officers (CEOs) of US academic medical centers were surveyed to elicit
their perceptions of board structures, activities, and attitudes reflecting 6
widely identified governance best practices; the relationship between use of
these practices and organizational performance, based on the University
HealthSystem Consortium's Quality & Accountability rankings, was assessed. High
performing hospitals showed greater use of all 6 practices, but the strongest
evidence supported a focus on board member education and development, the
rigorous use of performance measures to guide quality improvement, and systematic
board self-assessment processes. All hospitals, even those with the highest
quality ratings, had major gaps in their use of best practices for CEO and board
assessments. These findings can serve as the basis for developing sound board
improvement plans.
PMID- 25138783
TI - Impact of a pharmacy education program on chronic kidney disease patients with
complications in an outpatient clinic at police general hospital.
PMID- 25138779
TI - Genome-wide association study of maternal and inherited effects on left-sided
cardiac malformations.
AB - Congenital left-sided lesions (LSLs) are serious, heritable malformations of the
heart. However, little is known about the genetic causes of LSLs. This study was
undertaken to identify common variants acting through the genotype of the
affected individual (i.e. case) or the mother (e.g. via an in utero effect) that
influence the risk of LSLs. A genome-wide association study (GWAS) was performed
using data from 377 LSL case-parent triads, with follow-up studies in an
independent sample of 224 triads and analysis of the combined data. Associations
with both the case and maternal genotypes were assessed using log-linear analyses
under an additive model. An association between LSLs and the case genotype for
one intergenic SNP on chromosome 16 achieved genome-wide significance in the
combined data (rs8061121, combined P = 4.0 * 10(-9); relative risk to
heterozygote: 2.6, 95% CI: 1.9-3.7). In the combined data, there was also
suggestive evidence of association between LSLs and the case genotype for a
variant in the synaptoporin gene (rs1975649, combined P = 3.4 * 10(-7); relative
risk to heterozygote: 1.6, 95% CI: 1.4-2.0) and between LSLs and the maternal
genotype for an intergenic SNP on chromosome 10 (rs11008222, combined P = 6.3 *
10(-7); relative risk to heterozygote: 1.6, 95% CI: 1.4-2.0). This is the first
GWAS of LSLs to evaluate associations with both the case and maternal genotypes.
The results of this study identify three candidate LSL susceptibility loci,
including one that appears to be associated with the risk of LSLs via the
maternal genotype.
PMID- 25138784
TI - Analgesic efficacy of prophylactic gabapentin and lornoxicam in preventing
postendodontic pain.
AB - OBJECTIVE: In dental applications, as in all other medical applications, pain
needs to be prevented or at least controlled. The use of the tooth as a model for
studying pain mechanisms is well established. In the current study, we aimed to
evaluate and compare the analgesic effects of gabapentin and lornoxicam,
respectively, vs a placebo for postendodontic treatment pain. DESIGN AND METHODS:
Clinical research was planned as prospective, randomized, and placebo controlled.
Each subject was given 600 mg gabapentin (group G: N = 30), 8 mg lornoxicam
(group L: N = 30), or a placebo (group C: N = 30) 30 min prior to endodontic
treatment. OUTCOME MEASURES: At 4 (T(3)), 8 (T(4)), 12 (T(5)), and 24 (T(6)) h
after preoperative (T(0)) time points, the analgesic efficacies of the agents
were evaluated by using the visual analog scale (VAS). RESULTS: In group G, VAS
values were significantly greater at T(0) time point than at T(5) or T(6). T(0)
time point VAS value in group L was lower than at T4 time point and greater than
at T(6). In group C, T(0) time point VAS values were significantly lower at T(3)
and T(5) time points and greater than at T(6) time point. VAS values in group G
at T(5) time point were significantly lower than in group C or group L (P <
0.05). CONCLUSIONS: Based on the obtained data, prophylactic lornoxicam
controlled postendodontic treatment pain more effectively than did the placebo
drugs, and gabapentin was more effective in controlling the pain than either
lornoxicam or the placebo.
PMID- 25138786
TI - Increased serum levels of interleukin-18, -23 and -17 in Chinese patients with
Alzheimer's disease.
AB - AIMS: To evaluate the serum levels of interleukin (IL)-18, IL-23 and IL-17 in
Chinese patients with Alzheimer's disease (AD), and explore correlations between
the three cytokines and relevant parameters. METHODS: Serum concentrations of IL
18, IL-23 and IL-17 were measured by ELISA for 53 AD patients and 53 sex- and age
matched healthy controls in a community of elderly individuals in a Shanghai
suburb. RESULTS: Serum concentrations of IL-18, IL-23 and IL-17 were
significantly higher in AD patients than controls. The serum level of IL-23 was
observed to be significantly higher (p = 0.049) in female AD patients than male
AD patients. In addition, a significantly inverse correlation was found between
IL-18 and MMSE score (rs = -0.356, p = 0.011) for all AD patients. CONCLUSION:
Elevated IL-18, IL-23 and IL-17 levels are observed in AD patients and
differences may exist between males and females. Besides, IL-18 may correlate
with the severity of AD.
PMID- 25138785
TI - Relationship among 25-hydroxyvitamin D concentrations, insulin action, and
cardiovascular disease risk in patients with essential hypertension.
AB - BACKGROUND: Although low plasma 25-hydroxyvitamin D (25(OH)D) concentrations have
been shown to predict risk of hypertension and associated cardiovascular disease
(CVD), vitamin D repletion has not consistently lowered blood pressure or
decreased CVD. One possibility for this discrepancy is the presence of
considerable metabolic heterogeneity in patients with hypertension. To evaluate
this possibility, we quantified relationships among insulin resistance, 25(OH)D
concentration, and CVD risk factor profile in patients with essential
hypertension. METHODS: Measurements were made of 25(OH)D concentrations, multiple
CVD risk factors, and insulin resistance by the steady-state plasma glucose
concentration during the insulin suppression test in 140 otherwise healthy
patients with essential hypertension. RESULTS: As a group, the patients were
overweight/obese and insulin resistant and had low 25(OH)D concentrations. The
more insulin resistant the patients were, the worse the CVD risk profile was. In
addition, the most insulin-resistant quartile had significantly lower 25(OH)D
concentrations than the most insulin-sensitive quartile (20.3+/-1.4 vs. 25.8+/
1.4ng/ml; P = 0.005). In the entire group, 25(OH)D concentration significantly
correlated with magnitude of insulin resistance (steady-state plasma glucose
concentration; r = -0.20; P = 0.02). CONCLUSIONS: There was considerable
metabolic heterogeneity and substantial difference in magnitude of conventional
CVD risk factors in patients with similar degrees of blood pressure elevation.
The most insulin-resistant quartile of subjects had the lowest 25(OH)D
concentration and the most adverse CVD risk profile, and they may be the subset
of patients with essential hypertension most likely to benefit from vitamin D
repletion.
PMID- 25138787
TI - Usefulness of transient elastography by FibroScan for the evaluation of liver
fibrosis.
AB - INTRODUCTION: Liver stiffness measurement (LSM) is used for the assessment of
liver fibrosis. However, there is limited data in Indian patients. AIMS AND
OBJECTIVE: The aim of this study was to find the correlation of LSM, aspartate
transaminase to platelet ratio index (APRI) with fibrosis as assessed by liver
biopsy (LB), and predictors of discordance between LB and LSM. METHODS: One
hundred and eighty-five consecutive patients who underwent liver biopsy and
transient elastography (TE) were enrolled. Fibrosis was graded by two independent
pathologists using the METAVIR classification. Area under receiver operating
curves (AUROC) was used to evaluate the accuracy of transient elastography and
APRI in diagnosing significant fibrosis (F>2) and cirrhosis (F4). RESULTS:
Predominant etiologies were hepatitis B (46 %) and hepatitis C (26 %). LSM was
unsuccessful in ten patients (5 %) because of small intercostal space (n = 3) and
obesity (n = 7). Fibrosis is significantly correlated with LSM (r = 0.901, p =
0.001) and APRI (r = 0.736, p = 0.001). There was a significant difference in
median LSM value in patients with no fibrosis (F0) in comparison to patients
having mild fibrosis [mild portal fibrosis (F1) + fibrosis with few septa (F2)]
(4.5 vs. 7.5 kPa, p = 0.001) and advanced fibrosis [bridging fibrosis that is
spreading and connecting to other areas that contain fibrosis (F3) + cirrhosis or
advanced scarring of the liver (F4)] (4.5 vs. 19.4 kPa, p = 0.001). Similarly,
there was a significant difference in mean APRI value in patients with F0 in
comparison to patients having mild fibrosis (F1 + F2) (0.55 +/- 0.31 vs. 1.09 +/-
0.81, p = 0.001) and advanced fibrosis (F3 + F4) (2.3 +/- 1.3, p = 0.001). AUROC
for diagnosis of significant fibrosis was 0.98 (95 % confidence interval (CI)
0.963-0.999) for TE and 0.865 (95 % CI 0.810-0.920) for APRI. Optimal TE value
was 10.0 kPa for diagnosis of significant fibrosis and 14.7 kPa for cirrhosis
with specificity and sensitivity of 89 %, 98 % and 96 %, and 97 %, respectively.
On multivariate analysis, total bilirubin and histological activity index (HAI)
were identified as an independent predictor of TE inaccuracy. CONCLUSION: LSM is
a reliable predictor of hepatic fibrosis in Indian patients. LSM is superior to
APRI for noninvasive diagnosis of hepatic fibrosis and cirrhosis, and high
bilirubin (10.5 mg/dL) and Ishak HAI grade (>11) were independent predictors of
discordance between LB and LSM.
PMID- 25138789
TI - Regulation of angiopoietin-like protein 4 production during and after exercise.
AB - Angiopoietin-like protein 4 (ANGPTL4) may regulate lipoprotein lipase-dependent
plasma clearance of triacylglycerol from skeletal muscle during exercise. The aim
of this study was to examine the importance of muscle in regulating ANGPTL4 in
response to exercise. We sampled muscle biopsies and serum before, immediately
after, and 2 h after 45 min of ergometer cycling. Sampling was done before and
after a 12-week training intervention in controls and dysglycemic subjects.
Moreover, fat biopsies were taken before and after the training intervention. The
regulation of ANGPTL4 was also investigated in several tissues of exercising
mice, and in cultured myotubes. ANGPTL4 levels in serum and expression in muscle
were highest 2 h after exercise in both groups. Whereas ANGPTL4 was higher in
muscle of exercising controls as compared to dysglycemic subjects, the opposite
was observed in serum. In exercising mice, Angptl4 mRNA showed both higher basal
expression and induction in liver compared to muscle. Angptl4 mRNA was much
higher in adipose tissue than muscle and was also induced by exercise. We
observed two mRNA isoforms of ANGPTL4 in muscle and fat in humans. Both were
induced by exercise in muscle; one isoform was expressed 5- to 10-fold higher
than the other. Studies in mice and cultured myotubes showed that both fatty
acids and cortisol have the potential to increase ANGPTL4 expression in muscle
during exercise. In conclusion, ANGPTL4 is markedly induced in muscle in response
to exercise. However, liver and adipose tissue may contribute more than muscle to
the exercise-induced increase in circulating ANGPTL4.
PMID- 25138788
TI - Antibiotic use in acute pancreatitis: an Indian multicenter observational study.
AB - INTRODUCTION: Prophylactic antibiotics are used frequently for acute pancreatitis
(AP). Consensus guidelines do not recommend this currently, based on moderate
quality evidence. In this study, we aimed to evaluate the antibiotic use pattern
in AP in India and propose a risk-directed approach to antibiotic use in AP.
MATERIAL AND METHODS: This multicenter study was conducted from 1 May 2013 to 31
July 2013. Eleven participants from eight tertiary centers completed a
questionnaire that captured patient demographics, etiology, admission status,
presence of (peri)pancreatic necrosis, severity of pancreatitis, details of
antibiotic use, and clinical outcomes (total hospital stay, persistent organ
failure, need for ICU, total days in ICU, development of infections, in-hospital
mortality). RESULTS: A total of 200 proformas were analyzed. Seventy-three (36.5
%) had acute necrotizing pancreatitis (ANP). Eighty-nine (44.5 %), 52 (26 %), and
55 (27.5 %) patients had mild AP (MAP), moderately severe AP (MSAP), and severe
AP (SAP), respectively. Forty-five (22.5 %) patients developed infections
(unifocal 29; multifocal 16). One hundred thirty-four (67 %) patients received
antibiotics, of which 89 (66.4 %) received prophylactic, while 45 (33.6 %)
received therapeutic antibiotics. The distribution of antibiotic use according to
the severity of AP was 43 (48.3 %) in patients with MAP (prophylactic in 41;
therapeutic in 2), 36 (69.2 %) in patients with MSAP (prophylactic in 29;
therapeutic in 7), and 55 (100 %) in patients with SAP (prophylactic in 19;
therapeutic in 36). Therapeutic antibiotics were prescribed based on culture and
sensitivity in 21 (46.7 %) patients. CONCLUSIONS: Despite nonrecommendation,
prophylactic antibiotics are used frequently in AP. We emphasize on the need for
multicenter randomized controlled trials on prophylactic antibiotics for AP based
on a risk-directed approach, rather than a "blanket approach."
PMID- 25138790
TI - Identification of the pre-Botzinger complex inspiratory center in calibrated
"sandwich" slices from newborn mice with fluorescent Dbx1 interneurons.
AB - Inspiratory active pre-Botzinger complex (preBotC) networks produce the neural
rhythm that initiates and controls breathing movements. We previously identified
the preBotC in the newborn rat brainstem and established anatomically defined
transverse slices in which the preBotC remains active when exposed at one
surface. This follow-up study uses a neonatal mouse model in which the preBotC as
well as a genetically defined class of respiratory interneurons can be identified
and selectively targeted for physiological recordings. The population of
glutamatergic interneurons whose precursors express the transcription factor Dbx1
putatively comprises the core respiratory rhythmogenic circuit. Here, we used
intersectional mouse genetics to identify the brainstem distribution of Dbx1
derived neurons in the context of observable respiratory marker structures. This
reference brainstem atlas enabled online histology for generating calibrated
sandwich slices to identify the preBotC location, which was heretofore
unspecified for perinatal mice. Sensitivity to opioids ensured that slice rhythms
originated from preBotC neurons and not parafacial respiratory
group/retrotrapezoid nucleus (pFRG/RTN) cells because opioids depress preBotC,
but not pFRG/RTN rhythms. We found that the preBotC is centered ~0.4 mm caudal to
the facial motor nucleus in this Cre/lox reporter mouse during postnatal days 0
4. Our findings provide the essential basis for future optically guided
electrophysiological and fluorescence imaging-based studies, as well as the
application of other Cre-dependent tools to record or manipulate respiratory
rhythmogenic neurons. These resources will ultimately help elucidate the
mechanisms that promote respiratory-related oscillations of preBotC Dbx1-derived
neurons and thus breathing.
PMID- 25138793
TI - Erratum.
PMID- 25138791
TI - The exocyst and regulatory GTPases in urinary exosomes.
AB - Cilia, organelles that function as cellular antennae, are central to the
pathogenesis of "ciliopathies", including various forms of polycystic kidney
disease (PKD). To date, however, the molecular mechanisms controlling
ciliogenesis and ciliary function remain incompletely understood. A recently
proposed model of cell-cell communication, called "urocrine signaling",
hypothesizes that a subset of membrane bound vesicles that are secreted into the
urinary stream (termed exosome-like vesicles, or ELVs), carry cilia-specific
proteins as cargo, interact with primary cilia, and affect downstream cellular
functions. This study was undertaken to determine the role of the exocyst, a
highly conserved eight-protein trafficking complex, in the secretion and/or
retrieval of ELVs. We used Madin-Darby canine kidney (MDCK) cells expressing
either Sec10-myc (a central component of the exocyst complex) or Smoothened-YFP
(a ciliary protein found in ELVs) in experiments utilizing electron gold
microscopy and live fluorescent microscopy, respectively. Additionally, human
urinary exosomes were isolated via ultracentrifugation and subjected to mass
spectrometry-based proteomics analysis to determine the composition of ELVs. We
found, as determined by EM, that the exocyst localizes to primary cilia, and is
present in vesicles attached to the cilium. Furthermore, the entire exocyst
complex, as well as most of its known regulatory GTPases, are present in human
urinary ELVs. Finally, in living MDCK cells, ELVs appear to interact with primary
cilia using spinning disc confocal microscopy. These data suggest that the
exocyst complex, in addition to its role in ciliogenesis, is centrally involved
in the secretion and/or retrieval of urinary ELVs.
PMID- 25138792
TI - Acute insulin resistance stimulates and insulin sensitization attenuates vascular
smooth muscle cell migration and proliferation.
AB - Differential activation/deactivation of insulin signaling, PI-3K and MAP-K
pathways by high glucose and palmitate, with/out the insulin sensitizer
pioglitazone (PIO), have been previously shown in vascular smooth muscle cells
(VSMCs). To determine the biological impact of these molecular changes, we
examined VSMC migration and proliferation ("M"&"P") patterns in similar
conditions. VSMCs from healthy human coronary arteries were incubated in growth
medium and "M"&"P" were analyzed after exposure to high glucose (25 mmol/L) +/-
palmitate (200 MUmol/L) and +/- PIO (8 MUmol/L) for 5 h. "M"&"P" were assessed
by: (1) polycarbonate membrane barrier with chemo-attractants and extended cell
protrusions quantified by optical density (OD595 nm); (2) % change in radius area
(2D Assay) using inverted microscopy images; and (3) cell viability assay
expressed as cell absorbance (ABS) in media. "M" in 25 mmol/L glucose media
increased by ~25% from baseline and % change in radius area rose from ~20% to
~30%. The addition of PIO was accompanied by a significant decrease in "M" from
0.25 +/- 0.02 to 0.19 +/- 0.02; a comparable decline from 0.25 +/- 0.02 to 0.18
+/- 0.02 was also seen with 25 mmol/L of glucose +200 MUmol/L of palmitate. When
PIO was coincubated with high glucose plus palmitate there was a 50% reduction in
% change in radius. A ~10% increase in ABS, reflecting augmented "P" in media
with 25 mmol/L glucose versus control was documented. The addition of PIO reduced
ABS from 0.208 +/- 0.03 to 0.183 +/- 0.06. Both high glucose and palmitate showed
ABS of ~0.140 +/- 0.02, which decreased with PIO to ~0.120 +/- 0.02, indicating
"P" was reduced. CONCLUSION: These results confirm that high glucose and
palmitate stimulate VSMCs migration and proliferation in vitro, which is
attenuated by coincubation with the insulin sensitizer PIO. Although, we cannot
ascertain whether these functional changes are coincident with the
activation/deactivation of signal molecules, our findings are consistent with the
theory that differential regulation of insulin signaling pathways in VSMCs in
insulin-resistant states plays an important role in inflammation, arterial wall
thickening, and plaque formation during development of atherosclerosis.
PMID- 25138794
TI - Circuit-specific changes in D-serine-dependent activation of the N-methyl-D
aspartate receptor in the aging hippocampus.
AB - Age-related memory deficits have recently been associated with the impaired
expression of D-serine-dependent synaptic plasticity in neuronal networks of the
hippocampal CA1 area. However, whether such functional alterations are common to
the entire hippocampus during aging remains unknown. Here, we found that D-serine
was also required for the induction of N-methyl-D-aspartate receptor (NMDA-R)
dependent long-term potentiation (LTP) at perforant path-granule cell synapses of
the dentate gyrus. LTP as well as isolated NMDA-R synaptic potentials were
impaired in slices from aged rats, but in contrast to the CA1, this defect was
not reversed by exogenous D-serine. The lower activation of the glycine-binding
site by the endogenous co-agonist does not therefore appear to be a critical
mechanism underlying age-related deficits in NMDA-R activation in the dentate
gyrus. Instead, our data highlight the role of changes in presynaptic inputs as
illustrated by the weaker responsiveness of afferent glutamatergic fibers, as
well as changes in postsynaptic NMDA-R density. Thus, our study indicates that
although NMDA-R-dependent mechanisms driving synaptic plasticity are quite
similar between hippocampal circuits, they show regional differences in their
susceptibility to aging, which could hamper the development of effective
therapeutic strategies aimed at reducing cognitive aging.
PMID- 25138796
TI - Paraneoplastic neuropathy with positive anti-Hu. A case report.
PMID- 25138795
TI - Empyema due to Aggregatibacter aphrophilus and Parvimonas micra coinfection.
PMID- 25138797
TI - Intrathoracic schwannoma of the vagus nerve.
PMID- 25138798
TI - Thrombotic microangiopathy associated with tacrolimus in lung transplantation.
AB - Thrombotic microangiopathy (TMA) is a rare complication associated with the use
of calcineurin inhibitors in lung transplantation, irrespective of the underlying
disease of the graft recipient. It usually occurs in incomplete forms,
complicating and delaying diagnosis until damage is already irreversible. It is
unrelated to time from transplantation and often presents with concomitant
infection, which tends to confound diagnosis. The cases discussed here have a
common causative agent and all present with concomitant infection. Treatment
recommendations have changed in recent years with the introduction of
plasmapheresis or, more recently, the availability of the antibody eculizumab.
Notwithstanding, the most cost-effective measure is withdrawal or switching of
the calcineurin inhibitor. TMA is an underdiagnosed clinical entity that should
be considered in the management of transplantation patients.
PMID- 25138799
TI - Complementary home mechanical ventilation techniques. SEPAR Year 2014.
AB - This is a review of the different complementary techniques that are useful for
optimizing home mechanical ventilation (HMV). Airway clearance is very important
in patients with HMV and many patients, particularly those with reduced peak
cough flow, require airway clearance (manual or assisted) or assisted cough
techniques (manual or mechanical) and suctioning procedures, in addition to
ventilation. In the case of invasive HMV, good tracheostomy cannula management is
essential for success. HMV patients may have sleep disturbances that must be
taken into account. Sleep studies including complete polysomnography or
respiratory polygraphy are helpful for identifying patient-ventilator asynchrony.
Other techniques, such as bronchoscopy or nutritional support, may be required in
patients on HMV, particularly if percutaneous gastrostomy is required.
Information on treatment efficacy can be obtained from HMV monitoring, using
methods such as pulse oximetry, capnography or the internal programs of the
ventilators themselves. Finally, the importance of the patient's subjective
perception is reviewed, as this may potentially affect the success of the HMV.
PMID- 25138800
TI - Case-control study of anaemia among middle-aged and elderly women in three rural
areas of China.
AB - OBJECTIVES: To propose a feasible suggestion to reduce the high prevalence of
anaemia in middle-aged and elderly women by investigating risk factors,
particularly nutritional factors, and analysing the effect on anaemia in three
different rural areas of China. DESIGN: A case-control study. SETTING: Three
counties of China. PARTICIPANTS: Women aged 50-75 years in the three counties.
MAIN OUTCOME MEASURES: Adjusted OR (95% CI) of anaemia associated with diet,
lifestyle and blood biochemical indices. RESULTS: Compared with controls, women
with anaemia had lower body mass index (22.1 (3.2) kg/m(2) vs 23.2 (3.5) kg/m(2);
p<0.001), a higher experience of shortage of food (45.0% vs 36.5%; p<0.001), less
soy food intake (0.5 (0.3, 26.7) g/day vs 5.6 (0.4, 27.8) g/day; p<0.048), lower
serum iron (13.4 (5.4) MUmol/L vs 16.4 (5.7) MUmol/L; p<0.001), lower ferritin
(109.6 (85.6) ng/mL vs 131.0 (92.0) ng/mL; p<0.001), lower transferrin saturation
levels (22.5 (9.5)% vs 26.8 (9.6)%; p<0.001) and higher levels of free
erythrocyte protoporphyrin (42.4 (21.2) MUg/dL vs 39.6 (17.8) MUg/dL; p<0.001).
Anaemia was significantly associated with BMI(OR=0.90, 95% CI (0.87 to 0.92)),
food shortage experience (OR=1.39, 95% CI (1.15 to 1.69)), total protein
(OR=0.66, 95%CI (0.54 to 0.80)), Albumin (OR=0.72, 95%CI (0.59 to 0.87)) in
univariate analysis. Multivariate analysis showed that body mass index,
experience of food shortage, total protein and albumin were independently related
to anaemia. CONCLUSIONS: Among middle-aged and elderly women in rural China, the
nutrition status of anaemic cases is far below that of controls. Lower body mass
index and a greater experience of food shortage are closely related to anaemia.
Improving the blood protein status by consuming protein-sufficient foods such as
soy food is a feasible approach for elderly anaemic women. Further research is
needed on the effect of chronic inflammation and infectious disease on anaemia in
elderly women in rural China.
PMID- 25138802
TI - Third-wave cognitive therapy versus mentalisation-based treatment for major
depressive disorder: a randomised clinical trial.
AB - OBJECTIVE: To compare the benefits and harms of third-wave cognitive therapy
versus mentalisation-based therapy in a small sample of depressed participants.
SETTING: The trial was conducted at an outpatient psychiatric clinic for non
psychotic patients in Roskilde, Denmark. PARTICIPANTS: 44 consecutive adult
participants diagnosed with major depressive disorder. INTERVENTIONS: 18 weeks of
third-wave cognitive therapy (n=22) versus 18 weeks of mentalisation-based
treatment (n=22). OUTCOMES: The primary outcome was the Hamilton Rating Scale for
Depression (HDRS) at end of treatment (18 weeks). Secondary outcomes were:
remission (HDRS <8), Beck's Depression Inventory, Symptom Checklist 90 Revised
and The WHO-Five Well-being Index 1999. RESULTS: The trial inclusion lasted for
about 2 years as planned but only 44 out of the planned 84 participants were
randomised. Two mentalisation-based participants were lost to follow-up. The
unadjusted analysis showed that third-wave participants compared with
mentalisation-based participants did not differ significantly regarding the 18
weeks HDRS score (12.9 vs 17.0; mean difference -4.14; 95% CI -8.30 to 0.03;
p=0.051). In the analysis adjusted for baseline HDRS score, the difference was
favouring third-wave cognitive therapy (p=0.039). At 18 weeks, five of the third
wave participants (22.7%) were in remission versus none of the mentalisation
based participants (p=0.049). We recorded no suicide attempts or suicides during
the intervention period in any of the 44 participants. No significant differences
were found between the two intervention groups on the remaining secondary
outcomes. CONCLUSIONS: Third-wave cognitive therapy may be more effective than
mentalisation-based therapy for depressive symptoms measured on the HDRS.
However, more randomised clinical trials are needed to assess the effects of
third-wave cognitive therapy and mentalisation-based treatment for depression.
TRIAL REGISTRATION NUMBER: Registered with Clinical Trials government identifier:
NCT01070134.
PMID- 25138801
TI - Targeting intensive versus conventional glycaemic control for type 1 diabetes
mellitus: a systematic review with meta-analyses and trial sequential analyses of
randomised clinical trials.
AB - OBJECTIVE: To assess the benefits and harms of targeting intensive versus
conventional glycaemic control in patients with type 1 diabetes mellitus. DESIGN:
A systematic review with meta-analyses and trial sequential analyses of
randomised clinical trials. DATA SOURCES: The Cochrane Library, MEDLINE, EMBASE,
Science Citation Index Expanded and LILACS to January 2013. STUDY SELECTION:
Randomised clinical trials that prespecified different targets of glycaemic
control in participants at any age with type 1 diabetes mellitus were included.
DATA EXTRACTION: Two authors independently assessed studies for inclusion and
extracted data. RESULTS: 18 randomised clinical trials included 2254 participants
with type 1 diabetes mellitus. All trials had high risk of bias. There was no
statistically significant effect of targeting intensive glycaemic control on all
cause mortality (risk ratio 1.16, 95% CI 0.65 to 2.08) or cardiovascular
mortality (0.49, 0.19 to 1.24). Targeting intensive glycaemic control reduced the
relative risks for the composite macrovascular outcome (0.63, 0.41 to 0.96;
p=0.03), and nephropathy (0.37, 0.27 to 0.50; p<0.00001. The effect estimates of
retinopathy, ketoacidosis and retinal photocoagulation were not consistently
statistically significant between random and fixed effects models. The risk of
severe hypoglycaemia was significantly increased with intensive glycaemic targets
(1.40, 1.01 to 1.94). Trial sequential analyses showed that the amount of data
needed to demonstrate a relative risk reduction of 10% were, in general,
inadequate. CONCLUSIONS: There was no significant effect towards improved all
cause mortality when targeting intensive glycaemic control compared with
conventional glycaemic control. However, there may be beneficial effects of
targeting intensive glycaemic control on the composite macrovascular outcome and
on nephropathy, and detrimental effects on severe hypoglycaemia. Notably, the
data for retinopathy and ketoacidosis were inconsistent. There was a severe lack
of reporting on patient relevant outcomes, and all trials had poor bias control.
PMID- 25138803
TI - Incentivised case finding for depression in patients with chronic heart disease
and diabetes in primary care: an ethnographic study.
AB - OBJECTIVE: To examine the process of case finding for depression in people with
diabetes and coronary heart disease within the context of a pay-for-performance
scheme. DESIGN: Ethnographic study drawing on observations of practice routines
and consultations, debriefing interviews with staff and patients and review of
patient records. SETTING: General practices in Leeds, UK. PARTICIPANTS: 12
purposively sampled practices with a total of 119 staff; 63 consultation
observations and 57 patient interviews. MAIN OUTCOME MEASURE: Audio recorded
consultations and interviews with patients and healthcare professionals along
with observation field notes were thematically analysed. We assessed outcomes of
case finding from patient records. RESULTS: Case finding exacerbated the
discordance between patient and professional agendas, the latter already
dominated by the tightly structured and time-limited nature of chronic illness
reviews. Professional beliefs and abilities affected how case finding was
undertaken; there was uncertainty about how to ask the questions, particularly
among nursing staff. Professionals were often wary of opening an emotional 'can
of worms'. Subsequently, patient responses potentially suggesting emotional
problems could be prematurely shut down by professionals. Patients did not
understand why they were asked questions about depression. This sometimes led to
defensive or even defiant answers to case finding. Follow-up of patients
highlighted inconsistent systems and lines of communication for dealing with
positive results on case finding. CONCLUSIONS: Case finding does not fit
naturally within consultations; both professional and patient reactions somewhat
subverted the process recommended by national guidance. Quality improvement
strategies will need to take account of our results in two ways. First, despite
their apparent simplicity, the case finding questions are not consultation
friendly and acceptable alternative ways to raise the issue of depression need to
be supported. Second, case finding needs to operate within structured pathways
which can be accommodated within available systems and resources.
PMID- 25138804
TI - Overall, gender and social inequalities in suicide mortality in Iran, 2006-2010:
a time trend province-level study.
AB - OBJECTIVES: Suicide is a major global health problem imposing a considerable
burden on populations in terms of disability-adjusted life years. There has been
an increasing trend in fatal and attempted suicide in Iran over the past few
decades. The aim of the current study was to assess overall, gender and social
inequalities across Iran's provinces during 2006-2010. DESIGN: Ecological study.
SETTING: The data on distribution of population at the provinces were obtained
from the Statistical Centre of Iran. The data on the annual number of deaths
caused by suicide in each province were gathered from the Iranian Forensic
Medicine Organization. METHODS: Suicide mortality rate per 100,000 population was
calculated. Human Development Index was used as the provinces' social rank. Gini
coefficient, rate ratio and Kunst and Mackenbach relative index of inequality
were used to assess overall, gender and social inequalities, respectively. Annual
percentage change was calculated using Joinpoint regression. RESULTS: Suicide
mortality has slightly increased in Iran during 2006-2010. There was a
substantial and constant overall inequality across the country over the study
period. Male-to-female rate ratio was 2.34 (95% CI 1.45 to 3.79) over the same
period. There were social inequalities in suicide mortality in favour of people
in better-off provinces. In addition, there was an increasing trend in these
social disparities over time, although it was not statistically significant.
CONCLUSIONS: We found substantial overall, gender and social disparities in the
distribution of suicide mortality across the provinces in Iran. The findings
showed that men in the provinces with low socioeconomic status are at higher risk
of suicide mortality. Further analyses are needed to explain these disparities.
PMID- 25138805
TI - Geographic scale matters in detecting the relationship between neighbourhood food
environments and obesity risk: an analysis of driver license records in Salt Lake
County, Utah.
AB - OBJECTIVES: Empirical studies of the association between neighbourhood food
environments and individual obesity risk have found mixed results. One possible
cause of these mixed findings is the variation in neighbourhood geographic scale
used. The purpose of this paper was to examine how various neighbourhood
geographic scales affected the estimated relationship between food environments
and obesity risk. DESIGN: Cross-sectional secondary data analysis. SETTING: Salt
Lake County, Utah, USA. PARTICIPANTS: 403,305 Salt Lake County adults 25-64 in
the Utah driver license database between 1995 and 2008. ANALYSIS: Utah driver
license data were geo-linked to 2000 US Census data and Dun & Bradstreet business
data. Food outlets were classified into the categories of large grocery stores,
convenience stores, limited-service restaurants and full-service restaurants, and
measured at four neighbourhood geographic scales: Census block group, Census
tract, ZIP code and a 1 km buffer around the resident's house. These measures
were regressed on individual obesity status using multilevel random intercept
regressions. OUTCOME: Obesity. RESULTS: Food environment was important for
obesity but the scale of the relevant neighbourhood differs for different type of
outlets: large grocery stores were not significant at all four geographic scales,
limited-service restaurants at the medium-to-large scale (Census tract or larger)
and convenience stores and full-service restaurants at the smallest scale (Census
tract or smaller). CONCLUSIONS: The choice of neighbourhood geographic scale can
affect the estimated significance of the association between neighbourhood food
environments and individual obesity risk. However, variations in geographic scale
alone do not explain the mixed findings in the literature. If researchers are
constrained to use one geographic scale with multiple categories of food outlets,
using Census tract or 1 km buffer as the neighbourhood geographic unit is likely
to allow researchers to detect most significant relationships.
PMID- 25138806
TI - Multimorbidity in a marginalised, street-health Australian population: a
retrospective cohort study.
AB - OBJECTIVES: Demographic and presentation profile of patients using an innovative
mobile outreach clinic compared with mainstream practice. DESIGN: Retrospective
cohort study. SETTING: Primary care mobile street health clinic and mainstream
practice in Western Australia. PARTICIPANTS: 2587 street health and 4583
mainstream patients. MAIN OUTCOME MEASURES: Prevalence and patterns of chronic
diseases in anatomical domains across the entire age spectrum of patients and
disease severity burden using Cumulative Illness Rating Scale (CIRS). RESULTS:
Multimorbidity (2+ CIRS domains) prevalence was significantly higher in the
street health cohort (46.3%, 1199/2587) than age-sex-adjusted mainstream estimate
(43.1%, 2000/4583), p=0.011. Multimorbidity prevalence was significantly higher
in street health patients <45 years (37.7%, 615/1649) compared with age-sex
adjusted mainstream patients (33%, 977/2961), p=0.003 but significantly lower if
65+ years (62%, 114/184 vs 90.7%, 322/355, p<0.001). Controlling for age and
gender, the mean CIRS Severity Index score for street health (M=1.4, SD=0.91) was
significantly higher than for mainstream patients (M=1.1, SD=0.80), p<0.001.
Furthermore, 44.2% (530/1199) of street health patients had at least one level 3
or 4 score across domains compared with 18.3% (420/2294) for mainstream patients,
p<0.001. Street health population comprised 29.6% (766/2587) Aboriginal patients
with 50.4% (386/766) having multimorbidity compared with 44.6% (813/1821) for non
Aboriginals, p=0.007. There were no comprehensive data on Indigenous status in
the mainstream cohort available for comparison. Musculoskeletal, respiratory and
psychiatric domains were most commonly affected with multimorbidity significantly
associated with male gender, increasing age and Indigenous status. CONCLUSIONS:
Age-sex-adjusted multimorbidity prevalence and disease severity is higher in the
street health cohort. Earlier onset (23-34 years) multimorbidity is found in the
street health cohort but prevalence is lower in 65+ years than in mainstream
patients. Multimorbidity prevalence is higher for Aboriginal patients of all
ages.
PMID- 25138808
TI - Analgesia dose prescribing and estimated glomerular filtration rate decline: a
general practice database linkage cohort study.
AB - OBJECTIVE: We aimed to quantify the short-term effect of non-steroidal anti
inflammatory drugs (NSAIDs), aspirin and paracetamol analgesia dose prescribing
on estimated glomerular filtration rate (eGFR) decline in the general practice
population. DESIGN: A population-based longitudinal clinical data linkage cohort
study. SETTING: Two large general practices in North Staffordshire, UK.
PARTICIPANTS: Patients aged 40 years and over with >=2 eGFR measurements spaced
>=90 days apart between 1 January 2009 and 31 December 2010 were selected.
EXPOSURE: Using WHO Defined Daily Dose standardised cumulative analgesia
prescribing, patients were categorised into non-user, normal and high-dose
groups. OUTCOME MEASURE: The primary outcome was defined as a >5 mL/min/1.73
m(2)/year eGFR decrease between the first and last eGFR. Logistic regression
analyses were used to estimate risk, adjusting for sociodemographics,
comorbidity, baseline chronic kidney disease (CKD) status, renin-angiotensin
system inhibitors and other analgesia prescribing. RESULTS: There were 4145
patients (mean age 66 years, 55% female) with an analgesia prescribing prevalence
of 17.2% for NSAIDs, 39% for aspirin and 22% for paracetamol and stage 3-5 CKD
prevalence was 16.1% (n=667). Normal or high-dose NSAID and paracetamol
prescribing was not significantly associated with eGFR decline. High-dose aspirin
prescribing was associated with a reduced risk of eGFR decline in patients with a
baseline (first) eGFR >=60 mL/min/1.73 m(2); OR=0.52 (95% CI 0.35 to 0.77).
CONCLUSIONS: NSAID, aspirin and paracetamol prescribing over 2 years did not
significantly affect eGFR decline with a reduced risk of eGFR decline in high
dose aspirin users with well-preserved renal function. However, the long-term
effects of analgesia use on eGFR decline remain to be determined.
PMID- 25138809
TI - Evaluation of My Medication Passport: a patient-completed aide-memoire designed
by patients, for patients, to help towards medicines optimisation.
AB - OBJECTIVES: A passport-sized booklet, designed by patients for patients to record
details about their medicines, has been developed as part of a wider project
focusing on improving prescribing in the elderly ('ImPE'). We undertook an
evaluation of 'My Medication Passport' to gain an understanding of its value to
patients and how it may be used in communications about medicines. SETTING: The
Passport was launched in secondary care with the initial users being older people
discharged home after an admission to one of the four North West London
participating Trusts. The uptake subsequently spread to other (community)
locations and other age groups. PARTICIPANTS: We recruited more than 200 patients
from a cohort who had been given a passport as part of the improvement projects
at one of four sites. Of them, 63% (133) completed the structured telephone
questionnaire including 27% for whom English was not their first language.
Approximately half of the respondents were male and 40% were over 70 years of
age. RESULTS: More than half of the respondents had found their medication
passport useful or helpful in some way; 42% through sharing details from it with
others (most frequently family, carer or doctor) or using it as a platform for
conversations with healthcare professionals. One-third of those questioned
carried the passport with them at all times. CONCLUSIONS: My Medication Passport
has been positively evaluated; we have a better understanding of how it is used
by patients, what they are recording and how it can be an aid to dialogue about
medicines with family, carers and healthcare professionals. Further development
and spread is underway including an App for smartphones that will be subject to
wider evaluation to include feedback from clinicians.
PMID- 25138807
TI - MAXimising Involvement in MUltiMorbidity (MAXIMUM) in primary care: protocol for
an observation and interview study of patients, GPs and other care providers to
identify ways of reducing patient safety failures.
AB - INTRODUCTION: Increasing numbers of older people are living with multiple long
term health conditions but global healthcare systems and clinical guidelines have
traditionally focused on the management of single conditions. Having two or more
long-term conditions, or 'multimorbidity', is associated with a range of adverse
consequences and poor outcomes and could put patients at increased risk of safety
failures. Traditionally, most research into patient safety failures has explored
hospital or inpatient settings. Much less is known about patient safety failures
in primary care. Our core aims are to understand the mechanisms by which
multimorbidity leads to safety failures, to explore the different ways in which
patients and services respond (or fail to respond), and to identify opportunities
for intervention. METHODS AND ANALYSIS: We plan to undertake an applied
ethnographic study of patients with multimorbidity. Patients' interactions and
environments, relevant to their healthcare, will be studied through observations,
diary methods and semistructured interviews. A framework, based on previous
studies, will be used to organise the collection and analysis of field notes,
observations and other qualitative data. This framework includes the domains:
access breakdowns, communication breakdowns, continuity of care errors,
relationship breakdowns and technical errors. ETHICS AND DISSEMINATION: Ethical
approval was received from the National Health Service Research Ethics Committee
for Wales. An individual case study approach is likely to be most fruitful for
exploring the mechanisms by which multimorbidity leads to safety failures. A
longitudinal and multiperspective approach will allow for the constant comparison
of patient, carer and healthcare worker expectations and experiences related to
the provision, integration and management of complex care. This data will be used
to explore ways of engaging patients and carers more in their own care using
shared decision-making, patient empowerment or other relevant models.
PMID- 25138810
TI - Relationship between socioeconomic status and type 2 diabetes: results from Korea
National Health and Nutrition Examination Survey (KNHANES) 2010-2012.
AB - OBJECTIVE: To examine the relationship between socioeconomic status (SES) and
type 2 diabetes using the Korea National Health and Nutrition Examination Survey
(KNHANES) 2010-2012. DESIGN: A pooled sample cross-sectional study. SETTING: A
nationally representative population survey data. PARTICIPANTS: A total of 14,330
individuals who participated in the KNHANES 2010-2012 were included in our
analysis. PRIMARY OUTCOME: Prevalence of type 2 diabetes. RESULTS: The
relationship between SES and type 2 diabetes was assessed using logistic
regression after adjusting for covariates including age, gender, marital status,
region, body mass index, physical activity, smoking and high-risk drinking
behaviour. After adjustment for covariates, our results indicated that
individuals with the lowest income were more likely to have type 2 diabetes than
those with the highest income (OR 1.35; 95% CI 1.08 to 1.72). In addition, lower
educational attainment was an independent factor for a higher prevalence of type
2 diabetes in Korea. CONCLUSIONS: These findings suggest the need for developing
a health policy to ameliorate socioeconomic inequalities, in particular income
and education-related disparities in type 2 diabetes, along with risk factors at
the individual level. In addition, future investigations of type 2 diabetes among
Koreans should pay more attention to the social determinants of diabetes in order
to understand the various causes of the condition.
PMID- 25138811
TI - Decision aids for randomised controlled trials: a qualitative exploration of
stakeholders' views.
AB - OBJECTIVES: To explore stakeholders' perceptions of decision aids designed to
support the informed consent decision-making process for randomised controlled
trials. DESIGN: Qualitative semistructured interviews. Participants were provided
with prototype trial decision aids in advance to stimulate discussion. Interviews
were analysed using an established interpretive approach. PARTICIPANTS: 23
stakeholders: Trial Managers (n=5); Research Nurses (n=5); Ethics Committee
Chairs (n=5); patients (n=4) and Clinical Principal Investigators (n=4). SETTING:
Embedded within two ongoing randomised controlled trials. All interviews
conducted with UK-based participants. RESULTS: Certain key aspects (eg, values
clarification exercises, presentation of probabilities, experiences of others and
balance of options) in the prototype decision aids were perceived by all
stakeholders as having a significant advantage (over existing patient information
leaflets) in terms of supporting well informed appropriate decisions. However,
there were some important differences between the stakeholder groups on specific
content (eg, language used in the section on positive and negative features of
taking part in a trial and the overall length of the trial decision aids).
Generally the stakeholders believed trial decision aids have the potential to
better engage potential participants in the decision-making process and allow
them to make more personally relevant decisions about their participation.
CONCLUSIONS: Compared to existing patient information leaflets, stakeholders
perceived decision aids for trial participation to have the potential to promote
a more 'informed' decision-making process. Further efforts to develop, refine and
formally evaluate trial decision aids should be explored.
PMID- 25138812
TI - Comparison and validation of International Consensus Diagnostic Criteria for
diagnosis of autoimmune pancreatitis from pancreatic cancer in a Taiwanese
cohort.
AB - OBJECTIVES: The International Consensus Diagnostic Criteria (ICDC) designed to
diagnosis autoimmune pancreatitis (AIP) has been proposed recently. The
diagnostic performance of ICDC has not been previously evaluated in diffuse-type
and focal-type AIP, respectively, in comparison with the revised HISORt and Asian
criteria in Taiwan. DESIGN: Prospective, consecutive patient cohort. SETTING:
Largest tertiary referred centre hospital managing pancreatic disease in Taiwan.
PARTICIPANTS: 188 patients with AIP and 130 with tissue proofed pancreatic
adenocarcinoma were consecutively recruited. INTERVENTIONS: The ICDC, as well as
revised HISORt and Asian criteria, was applied for each participant. Each
diagnostic criterion of ICDC was validated with special reference to levels 1 and
2 in diffuse-type and focal-type AIP. OUTCOMES: Sensitivity, specificity and
accuracy. Each diagnostic criterion of ICDC was validated with special reference
to levels 1 and 2 in AIP and focal-type AIP. RESULTS: The sensitivity,
specificity and accuracy of ICDC for all AIP were the best: 89.4%, 100% and
93.7%, respectively, in these three criteria. The sensitivity, specificity and
accuracy of ICDC for focal-type AIP (84.9%, 100% and 93.8%) were also the best
among these three criteria. The area under the curve of receiver-operator
characteristic of ICDC was 0.95 (95% CI 0.92 to 0.97) in all AIP and 0.93 (95% CI
0.88 to 0.97) in focal-type AIP. CONCLUSIONS: The sensitivity, specificity and
accuracy of ICDC are higher than the revised HISORt and Asian criteria. The
sensitivity, specificity and accuracy of each criterion are higher in diffuse
type AIP compared with focal-type AIP. Under the same specificity, the
sensitivity and accuracy of ICDC are higher than other diagnostic criteria in
focal-type AIP. ICDC has better diagnostic performance compared with previously
proposed diagnostic criteria in diffuse-type and focal-type AIP.
PMID- 25138813
TI - A community-based survey for different abnormal glucose metabolism among pregnant
women in a random household study (SAUDI-DM).
AB - OBJECTIVE: To assess the prevalence and risk factors of gestational diabetes
mellitus (GDM) in a population known to have a high prevalence of abnormal
glucose metabolism. METHODS: A household random population-based cross-sectional
study of 13,627 women in the childbearing age, who were subjected to fasting
plasma glucose if they were not known to have been diagnosed before with any type
of diabetes. GDM cases were diagnosed using the International Association of
Diabetes and Pregnancy Study Group (IAPSG) criteria. RESULTS: The overall GDM
prevalence was 36.6%, categorised into 32.4% new cases and 4.2% known cases.
Another 3.6% had preconception type 1 or 2 diabetes. GDM cases were older and had
a significantly higher body mass index, in addition to a higher rate of
macrocosmic baby and history of GDM. Monthly income, educational level, living in
urban areas and smoking were not found to be significantly different between
normal and GDM cases. The most important and significant risk factors for GDM
were history of GDM, macrosomic baby, obesity and age >30 years. However,
hypertension, low high-density lipoprotein, family history of diabetes and
increased triglycerides did not show any significant effect on GDM prevalence in
this cohort. CONCLUSIONS: This society is facing a real burden of abnormal
glucose metabolism during pregnancy, where almost half of the pregnant women are
subjected to maternal and neonatal complications. Early screening of pregnant
women, especially those at a high risk for GDM, is mandatory to identify and
manage those cases.
PMID- 25138814
TI - A study protocol for a randomised open-label clinical trial of artesunate
mefloquine versus chloroquine in patients with non-severe Plasmodium knowlesi
malaria in Sabah, Malaysia (ACT KNOW trial).
AB - INTRODUCTION: Malaria due to Plasmodium knowlesi is reported throughout South
East Asia, and is the commonest cause of it in Malaysia. P. knowlesi replicates
every 24 h and can cause severe disease and death. Current 2010 WHO Malaria
Treatment Guidelines have no recommendations for the optimal treatment of non
severe knowlesi malaria. Artemisinin-combination therapies (ACT) and chloroquine
have each been successfully used to treat knowlesi malaria; however, the rapidity
of parasite clearance has not been prospectively compared. Malaysia's national
policy for malaria pre-elimination involves mandatory hospital admission for
confirmed malaria cases with discharge only after two negative blood films; use
of a more rapidly acting antimalarial agent would have health cost benefits. P.
knowlesi is commonly microscopically misreported as P. malariae, P. falciparum or
P. vivax, with a high proportion of the latter two species being chloroquine
resistant in Malaysia. A unified ACT-treatment protocol would provide effective
blood stage malaria treatment for all Plasmodium species. METHODS AND ANALYSIS:
ACT KNOW, the first randomised controlled trial ever performed in knowlesi
malaria, is a two-arm open-label trial with enrolments over a 2-year period at
three district sites in Sabah, powered to show a difference in proportion of
patients negative for malaria by microscopy at 24 h between treatment arms
(clinicaltrials.gov #NCT01708876). Enrolments started in December 2012, with
completion expected by September 2014. A total sample size of 228 is required to
give 90% power (alpha 0.05) to determine the primary end point using intention-to
treat analysis. Secondary end points include parasite clearance time, rates of
recurrent infection/treatment failure to day 42, gametocyte carriage throughout
follow-up and rates of anaemia at day 28, as determined by survival analysis.
ETHICS AND DISSEMINATION: This study has been approved by relevant institutional
ethics committees in Malaysia and Australia. Results will be disseminated to
inform knowlesi malaria treatment policy in this region through peer-reviewed
publications and academic presentations. TRIAL REGISTRATION NUMBER: NCT01708876.
PMID- 25138817
TI - Implementation and use of electronic synoptic cancer reporting: an explorative
case study of six Norwegian pathology laboratories.
AB - BACKGROUND: The information contained in histopathology reports on surgical
resections of cancer is fundamental for both patient treatment and cancer
registries. Electronic synoptic histopathology reporting is considered superior
to traditional narrative reporting with respect to both completeness and
feasibility of data use. An electronic template for colorectal cancer reporting
was introduced in Norway in 2005, but implementation has varied greatly between
different pathology departments. In 2012, four pathology departments and the
Norwegian Cancer Registry started a new initiative on electronic cancer
reporting. As part of this initiative, this study was undertaken to learn more
about factors influencing implementation and use. METHODS: Qualitative and
quantitative data were obtained from six of the 17 public pathology departments
in Norway using explorative case study methodology. Methods included document
studies, semi-structured interviews with key informants, and audits on actual
template use. A systematic analysis of data was conducted based on theoretical
models for project management, stakeholder engagement, and individual acceptance
of new information technology. RESULTS: Most key informants had a positive view
on synoptic reporting, and five departments had tested the electronic template.
Of these, four had implemented the template while one department had decided not
to implement it due to layout concerns. Of the four departments using the
template in daily routine, one had compulsory use, two consensus based use, while
the fourth had voluntary use. Annual average usage of the electronic template in
the three departments with compulsory or consensus based use was 92% compared to
53% in the department with voluntary use. CONCLUSIONS: There was a general
positive attitude towards electronic synoptic reporting. Reasons for not
implementing the colorectal template were specific technical and quality issues
not adequately addressed by the project organization having developed the
template. A formal assessment of project outcomes with a task force handling such
technical issues should accordingly have been established as part of the project.
After an organizational decision on implementation, perceived job relevance and
practical benefits are factors important for individual template use. Consistent
high long-term usage was related to a departmental environment with a consensus
based decision on use.
PMID- 25138815
TI - Protocol for the RT Prepare Trial: a multiple-baseline study of radiation
therapists delivering education and support to women with breast cancer who are
referred for radiotherapy.
AB - INTRODUCTION: There is limited evidence to guide the preparation of patients for
radiotherapy. This paper describes the protocol for an evaluation of a radiation
therapist led education intervention delivered to patients with breast cancer in
order to reduce psychological distress. METHODS: A multiple-baseline study is
being used. Usual care data is being collected prior to the start of the
intervention at each of three sites. The intervention is delivered by radiation
therapists consulting with patients prior to their treatment planning and on the
first day of treatment. The intervention focuses on providing sensory and
procedural information to patients and reducing pretreatment anxiety. Recruitment
is occurring in three states in Australia. Eligible participants are patients who
have been referred for radiotherapy to treat breast cancer. 200 patients will be
recruited during a usual care phase and, thereafter, 200 patients in the
intervention phase. Measures will be collected on four occasions-after meeting
with their radiation oncologist, prior to treatment planning, on the first day of
treatment and after treatment completion. The primary hypothesis is that patients
who receive the radiotherapy preparatory intervention will report a significantly
greater decrease in psychological distress from baseline to prior to radiotherapy
treatment planning in comparison with the usual care group. Secondary outcome
measures include concerns about radiotherapy, patient knowledge of radiotherapy,
patient preparedness and quality of life. Patient health system usage and costs
will also be measured. Multilevel mixed effects regression models will be applied
to test for intervention effects. ETHICS: Ethics approval has been gained from
Curtin University and the three recruiting sites. DISSEMINATION: Results will be
reported in international peer reviewed journals. TRIAL REGISTRATION NUMBER:
Australian and New Zealand Clinical Trials Registration: ACTRN12611001000998.
PMID- 25138819
TI - Dissection of the posterior wall by guide-wire during internal jugular vein
catheterization.
AB - We report a case of posterior wall hematoma formation in the internal jugular
vein after the puncture of central vein. An 82-year-old woman was scheduled for
laparotomy for an abdominal incisional hernia. After induction of general
anesthesia, we performed central venous catheterization via the right internal
jugular vein under ultrasound guidance in the short-axis view and out-of plane
technique. The ultrasound view after insertion of a guide-wire revealed a
hematoma-like space on the posterior wall of the vein. We removed and reinserted
the guide-wire. This time, insertion of the wire and catheter was uneventful.
Seven days after the surgery, no hematoma-like space was found in the vein. The
malposition of the guide-wire was detected before dilation, which enabled us to
avoid complications in this case. We should note that the confirmation of guide
wire placement in the vein is important during ultrasound-guided central venous
catheterization.
PMID- 25138816
TI - Structural analysis of diheme cytochrome c by hydrogen-deuterium exchange mass
spectrometry and homology modeling.
AB - A lack of X-ray or nuclear magnetic resonance structures of proteins inhibits
their further study and characterization, motivating the development of new ways
of analyzing structural information without crystal structures. The combination
of hydrogen-deuterium exchange mass spectrometry (HDX-MS) data in conjunction
with homology modeling can provide improved structure and mechanistic
predictions. Here a unique diheme cytochrome c (DHCC) protein from Heliobacterium
modesticaldum is studied with both HDX and homology modeling to bring some
definition of the structure of the protein and its role. Specifically, HDX data
were used to guide the homology modeling to yield a more functionally relevant
structural model of DHCC.
PMID- 25138818
TI - Skeletal versus conventional intraoral anchorage for the treatment of class II
malocclusion: dentoalveolar and skeletal effects.
AB - BACKGROUND: The purpose of this retrospective study is to investigate the
dentoalveolar and skeletal effects of two distalizing protocols featuring
different anchorage systems used in patients with class II malocclusion: the MGBM
system (skeletal anchorage) and Pendulum (intraoral anchorage). METHODS: The
sample comprised 57 patients who were assigned to one of the two treatments: the
MGBM group (30 patients, mean age 13.3 +/- 2.3 years) or the Pendulum group (27
patients, mean age 12.8 +/- 1.7 years). Three serial cephalograms were obtained
at baseline (T0), after molar distalization (T1), and after fixed appliance
treatment (T2). Esthetic, skeletal, and dental parameters were considered.
Pancherz's superimposition method was used to assess sagittal dental changes. The
initial and final measurements and treatment changes were compared by means of a
paired t test or a paired Wilcoxon test. Statistical significance was tested at p
< 0.05, p < 0.01, and p < 0.001. RESULTS: In the MGBM group, the upper molar
distalization was achieved in 7 months and showed a mean value of 4.9 mm (ms
PLO); the amount of molar relationship correction was 5.9 mm. In the Pendulum
group, the upper molar distalization was obtained in 9 months and showed a mean
value of 2.5 mm (ms-PLO), while the molar relationship correction amounted to 4.9
mm. Anterior anchorage loss occurred in both groups, although in the MGBM group,
there was less mesial movement of the premolars. CONCLUSIONS: The MGBM system and
the Pendulum appliance are both effective in the correction of class II
malocclusions. The MGBM system was found to be more efficient than the Pendulum
appliance, producing greater molar distalization in a shorter treatment time.
PMID- 25138821
TI - Anisocoria after anesthesia induction caused by Adie syndrome.
PMID- 25138820
TI - An unusual case of post-anaesthesia voice loss.
PMID- 25138822
TI - An assessment of the awareness of local anesthetic systemic toxicity among multi
specialty postgraduate residents.
AB - Local anesthetics (LAs) are extensively used in clinical practice by both
anesthesiologists and non-anesthesiologists and are often associated with
systemic toxicity. We hypothesize that this awareness is inadequate among medical
specialists and entails a risk of misdiagnosis and underreporting of such events.
We therefore conducted a cross-sectional questionnaire-based study to assess the
level of understanding of LA use and effective management of systemic toxicity
among 200 postgraduate residents of various specialties (with the exception of
anesthesiology) in a tertiary care hospital in India from October to December
2013. Among those residents who had used LAs (193/200), 27 and 25 % of responders
correctly identified the toxic doses of lidocaine and of lidocaine + adrenaline,
respectively. Of the responders, 70 % always performed a negative aspiration of
blood before injecting the drug, 27 % sometimes aspirated and the remaining 3 %
never aspirated. The majority of the responders (93 %) were unaware of the toxic
dose of bupivacaine. Only 70 % of responders believed that LAs could be toxic [95
% confidence interval (CI) 65.5-74.5 %], and 81 % of these correctly identified
the signs and symptoms of cardiotoxicity. Only 2 % of responders knew that lipid
emulsion is a part of its treatment (95 % CI 0.6-3.4 %). Based on these results,
there is a definite need to increase the awareness of detection and treatment of
local anesthetic toxicity among all medical practitioners who regularly use LAs.
PMID- 25138823
TI - Anterior temporal atrophy and posterior progression in patients with Parkinson's
disease.
AB - BACKGROUND: Parkinson's disease (PD) is characterized by specific motor and
nonmotor impairments. This suggests that PD is characterized by disease-specific
regional cortical atrophy. Given the change of symptoms over time, a concurrent
increase in regional atrophy may further be assumed to reflect the dynamic
process of disease progression. METHODS: In this study we retrospectively
collected T1-weighted MRI scans from previous studies performed in our center,
enabling the comparison of gray matter atrophy in 77 PD patients with 87 controls
using voxel-based morphometry (VBM). This large VBM analysis provided the
opportunity to investigate cortical atrophy in relation with disease progression.
RESULTS: We found significant PD-related reductions of gray matter density
bilaterally in the anterior temporal cortex, the left inferior frontal and left
extrastriate visual cortex, independent from normal aging. The anterior temporal
cortex did not show major progression, whereas particularly the posterior parts
of the lateral temporal cortex and adjacent extrastriate visual cortex occurred
at a later stage of disease. CONCLUSIONS: Temporal pole atrophy as an early sign
of PD is consistent with the PD pathology classification of Braak. The initial
anterior temporal atrophy with spread to occipitotemporal and posterior parietal
regions may subserve 'emotion-based' sensorimotor transformations and deficits in
the visual domain, respectively, which may be regarded as premotor symptoms.
PMID- 25138824
TI - Uterine fibroid research: a work in progress.
PMID- 25138825
TI - Enodthelin 1 is elevated in plasma and explants from patients having uterine
leiomyomas.
AB - OBJECTIVE: To determine a role for endothelin (ET) in progression of uterine
fibroids. DESIGN: An in vitro model of fibroid and myometrium cultivation.
PATIENTS: A total of 32 women undergoing hysterectomies for uterine fibroids and
11 women undergoing hysterectomies for abnormal uterine bleeding (control
population). RESULTS: Women with uterine fibroids were hypertensive and displayed
significantly greater circulating ET-1 compared to control patients. Secretion of
ET-1 was greater from the fibroids compared to myometrium explants. Endothelin 1
secretion was attenuated with blockade of the angiotensin II type 1 or
endothelinA receptors. Hypoxia stimulated ET-1 secretion from both myometrium and
fibroid explants. Preproendothelin messenger RNA expression increased with
hypoxia from fibroid explants compared to normoxic controls. CONCLUSIONS: These
data support the hypothesis that uterine fibroids are associated with
hypertension and increased ET-1, which is exacerbated with hypoxia. These data
suggest a possible link between mechanisms of blood pressure regulation and
development of uterine leiomyoma.
PMID- 25138826
TI - Management of hypertension and heart failure in patients with Addison's disease.
AB - Addison's disease may be complicated by hypertension and less commonly by heart
failure. We review the pathophysiology of the renin-angiotensin-aldosterone axis
in Addison's disease and how this is altered in the setting of hypertension and
heart failure. An essential first step in management in both conditions is
optimizing glucocorticoid replacement and considering dose reduction if
excessive. Following this, if a patient with Addison's disease remains
hypertensive, the fludrocortisone dose should be reviewed and reduced if there
are clinical and/or biochemical signs of mineralocorticoid excess. In the absence
of such signs, where the renin is towards the upper end of the normal range or
elevated, an angiotensin II (AII) receptor antagonist or angiotensin converting
enzyme (ACE) inhibitor is the treatment of choice, and the fludrocortisone dose
should remain unchanged. Dihydropyridine calcium channel blockers are clinically
useful as second line agents, but diuretics should be avoided. In the setting of
heart failure, there is an increase in total body sodium and water; therefore, it
is appropriate to reduce and rarely consider ceasing the fludrocortisone. Loop
diuretics may be used, but not aldosterone antagonists such as spironolactone or
eplerenone. Standard treatment with ACE inhibitors, or as an alternative, AII
receptor antagonists, are appropriate. Measurements of renin are no longer
helpful in heart failure to determine the volume status but plasma levels of
brain natriuretic peptide (BNP/proBNP) may help guide therapy.
PMID- 25138827
TI - The importance of nanoparticle shape in cancer drug delivery.
AB - INTRODUCTION: Nanoparticles have been successfully used for cancer drug delivery
since 1995. In the design of commercial nanoparticles, size and surface
characteristics have been exploited to achieve efficacious delivery. However, the
design of optimized drug delivery platforms for efficient delivery to disease
sites with minimal off-target effects remains a major research goal. One crucial
element of nanoparticle design influencing both pharmacokinetics and cell uptake
is nanoparticle morphology (both size and shape). In this succinct review, the
authors collate the recent literature to assess the current state of
understanding of the influence of nanoparticle shape on the effectiveness of drug
delivery with a special emphasis on cancer therapy. AREAS COVERED: This review
draws on studies that have focused on the role of nonspherical nanoparticles used
for cancer drug delivery. In particular, the authors summarize the influence of
nanoparticle shape on biocirculation, biodistribution, cellular uptake and
overall drug efficacy. By comparing spherical and nonspherical nanoparticles,
they establish some general design principles to serve as guidelines for
developing the next generation of nanocarriers for drug delivery. EXPERT OPINION:
Pioneering studies on nanoparticles show that nonspherical shapes show great
promise as cancer drug delivery vectors. Filamentous or worm-like micelles
together with other rare morphologies such as needles or disks may become the
norm for next-generation drug carriers, though at present, traditional spherical
micelles remain the dominant shape of nanocarriers described in the literature
due to synthesis and testing difficulties. The few reports that do exist
describing nonspherical nanoparticles show a number of favorable properties that
should encourage more efforts to develop facile and versatile nanoparticle
synthesis methodologies with the flexibility to create different shapes, tunable
sizes and adaptable surface chemistries. In addition, the authors note that there
is a current lack of understanding into the factors governing (and optimizing)
the inter-relationships of size, surface characteristics and shapes of many
nanoparticles proposed for use in cancer therapy.
PMID- 25138831
TI - We need to help nurses practise what they preach.
AB - Are you heavier than you would like to be? Nurses would no doubt respond in much
the same way as any other group of people, with many saying 'yes' in response.
The question is whether healthcare professionals should feel obliged to set a
good example by living healthy lifestyles.
PMID- 25138830
TI - Editorial Comment to Positron emission tomography/magnetic resonance imaging with
68Gallium-labeled ligand of prostate-specific membrane antigen: promising novel
option in prostate cancer imaging?
PMID- 25138828
TI - Metal nanobullets for multidrug resistant bacteria and biofilms.
AB - Infectious diseases were one of the major causes of mortality until now because
drug-resistant bacteria have arisen under broad use and abuse of antibacterial
drugs. These multidrug-resistant bacteria pose a major challenge to the effective
control of bacterial infections and this threat has prompted the development of
alternative strategies to treat bacterial diseases. Recently, use of metallic
nanoparticles (NPs) as antibacterial agents is one of the promising strategies
against bacterial drug resistance. This review first describes mechanisms of
bacterial drug resistance and then focuses on the properties and applications of
metallic NPs as antibiotic agents to deal with antibiotic-sensitive and
resistant bacteria. We also provide an overview of metallic NPs as bactericidal
agents combating antibiotic-resistant bacteria and their potential in vivo
toxicology for further drug development.
PMID- 25138833
TI - RCN head of policy says costs of nurse training pilot are prohibitive.
AB - A quarter of the 250 prospective nursing students recruited to a national
training pilot set up to give them up to a year's caring experience have not
pursued nursing as a career, Nursing Standard has learned.
PMID- 25138834
TI - NMC offers nurses instalment option on paying annual registration fees.
AB - The Nursing and Midwifery Council (NMC) is asking nurses if they would like the
option to pay their annual L100 registration fee in instalments.
PMID- 25138835
TI - College lobbies to keep NHS out of EU-US trade deal.
AB - The RCN will begin lobbying European Union politicians and officials in the
autumn to exclude health services from a controversial free trade agreement being
negotiated between Europe and the United States.
PMID- 25138836
TI - Draft code is 'patronising' and too long, says RCN.
AB - A proposed new code of practice for nurses drawn up by the Nursing and Midwifery
Council (NMC) has been criticised as 'prescriptive and patronising' by the RCN.
PMID- 25138837
TI - Unions considering joint action in the autumn over pay award.
AB - Thousands of NHS nurses, midwives and other staff may walk out of work for four
hours in mid-October in a protest over pay.
PMID- 25138839
TI - As you were in first world war nursing.
AB - Nursing students dressed up in uniforms from 100 years ago to commemorate the
contribution of healthcare workers in the first world war.
PMID- 25138840
TI - All hospitals need i.v. therapy lead to reduce incidents, advises NICE.
AB - Every hospital should appoint a lead for intravenous (i.v.) fluids to reduce the
frequency of complications occurring, says a new quality standard published last
week by the National Institute for Health and Clinical Excellence (NICE).
PMID- 25138842
TI - Yacker trackers could help keep noise down on wards.
AB - A hospital in Australia may introduce 'yacker trackers'--devices that alert staff
when there is excessive noise.
PMID- 25138843
TI - Medication review saves nurses' time.
AB - A project involving care home nurses that led to a significant reduction in
unnecessary prescribing has saved around an hour a day of nursing time.
PMID- 25138844
TI - Audit uncovers weak skill mix.
AB - More than a quarter of hospital wards in Wales do not have the nursing skill mix
recommended by the chief nursing officer, according to an audit.
PMID- 25138845
TI - NSPCC tests staff values at mental health trust.
AB - A child protection charity is training NHS recruiters to recognise which nurses
are compassionate and caring enough to employ.
PMID- 25138847
TI - Meet Jon Billings, the man charged with modernising the NMC's image.
AB - For the past year and a half the Nursing and Midwifery Council (NMC) has been a
hive of activity as it tries to repair its tarnished reputation. Barely a month
goes by without nurses being consulted on some proposed change, a requirement
under the NMC's governing legislation.
PMID- 25138853
TI - Bariatric surgery.
AB - Essential facts: Type 2 diabetes is linked closely to obesity. Bariatric surgery
can lead to dramatic improvements in the management of the condition, according
to the National Institute for Health and Care Excellence (NICE). There are two
main types of bariatric surgery. A gastric band procedure uses a band to reduce
the size of the stomach so a smaller amount of food is required to make the
patient feel full. A gastric bypass is where the digestive system is re-routed
past most of the stomach so less food is digested.
PMID- 25138854
TI - Loosening the belt on weight loss procedures.
PMID- 25138855
TI - From NHS to army--and back again.
PMID- 25138869
TI - Help for overseas nurses unable to obtain supervised placements.
AB - Nurses from outside the European Economic Area looking to work in the UK will no
longer have to complete supervised practice placements (News August 6).
PMID- 25138868
TI - The NMC is taking too long to process overseas applications.
AB - As acting head of nursing and midwifery education at Portsmouth Hospitals NHS
Trust, I would like to comment on 'Supervised placements will be scrapped for
staff coming to the UK' (News August 6).
PMID- 25138870
TI - If hospital nurses are to lose weight, the NHS needs to provide more food.
AB - The focus on food in hospitals is invariably on the patients. So it is good to
read that NHS England chief executive Simon Stevens is concerned by rising
obesity rates and the health of his employees (Analysis August 13).
PMID- 25138871
TI - Fill in our survey to help foster a culture of health and fitness.
AB - On behalf of the University of Aberdeen, I am inviting nurses to complete an
online national survey on the influences on their eating and physical activity
for managing body weight.
PMID- 25138873
TI - Seacole Statue Appeal reaches another important milestone.
AB - As associate director of the NHS Confederation, I am delighted to have been
appointed an ambassador for the Mary Seacole Statue Appeal.
PMID- 25138874
TI - A renationalised health service would drive down supply costs.
AB - 'Politicians alienate nurses at their peril' and 'L32 for 100 wipes--what a waste
of NHS money' (Editorial and News July 30) highlight poor procurement policies in
the NHS.
PMID- 25138875
TI - End of life care services for patients with heart failure.
AB - Heart failure has high incidence and prevalence in the UK. However, access to
palliative care services for patients with heart failure is inequitable. Patients
with heart failure often do not receive specialist palliative care at the end of
life, or referral is made only in the last days of life. This results in lost
opportunities for advance care planning, psychological support for patients and
families and symptom management. Prognostic tools are useful in ensuring
appropriate referral. However, the controversy regarding the Liverpool Care
Pathway has created uncertainty for healthcare professionals, patients and
families. This article examines palliative care and end of life care services for
patients with heart failure. It presents the case for service development and
examines the benefits for patients who traditionally may not have had access to
this care.
PMID- 25138876
TI - A parent information leaflet to promote mental health in children.
AB - Positive mental health is an essential element of every child's overall health
and lays the building blocks for mentally healthy adults. There is increasing
emphasis on childhood mental health as a public health issue. Nurses should be
able to provide parents with clear, practical and accurate information to promote
and maintain positive childhood mental health. This article describes the
background to, and development and piloting of, My Mind Matters Too, a parent
information leaflet promoting positive mental health for young children. The
leaflet cannot operate in a vacuum but must be combined with other services and
interventions if it is to bring about changes in the often complex area of
childhood mental health.
PMID- 25138877
TI - Psychological interventions in obsessive compulsive disorder.
AB - Obsessive compulsive disorder (OCD) is a common mental health problem associated
with poor quality of life, impaired functioning and increased risk of suicide.
Improvement is unlikely and symptoms will remain chronic unless adequate
treatment is provided. National Institute for Health and Care Excellence (2006a)
guidelines on the management of OCD, recommend the use of psychological
treatments that are based on cognitive behavioural therapy (CBT). Brief treatment
forms of CBT are recommended initially and more intensive forms are offered when
health gain is not apparent. While the presentation of OCD can be complex, nurses
can assist in the recognition and treatment of OCD through additional training or
current skills.
PMID- 25138878
TI - Statins.
AB - While I was aware of the link between high serum cholesterol and cardiovascular
disease, I was unaware of the mechanism of atheroma development. The CPD article
discussed the role of low-density lipoprotein in the development of
atherosclerosis, which I found very interesting.
PMID- 25138880
TI - New enticements to return to nursing.
AB - There are many benefits of supporting former registered nurses back into practice
and on to the Nursing and Midwifery Council register.
PMID- 25138879
TI - Carers need care too.
AB - NHS staff wellbeing has been high on the agenda since the Boorman review
concluded that many organisations made insufficient investment in this area of
employee welfare.
PMID- 25138883
TI - Student life--a template for good care.
AB - A personal philosophy of nursing is a strategy that nurses can use to affirm that
their practice is in harmony with their values.
PMID- 25138884
TI - Well trained in understanding.
AB - Healthcare assistants (HCAs) at Milton Keynes Hospital NHS Foundation Trust have
been busy with a series of clinical training programmes run for them by the
nearby Open University.
PMID- 25138887
TI - A course that allows me to fulfil my dream of nursing.
AB - As a mature student with many life experiences, I always wanted to be a nurse,
and the opportunity to study at BPP University school of health offered me the
chance to fulfil my dream. The university's higher education certificate in
health and social care allows students to apply for nurse training.
PMID- 25138888
TI - The memory services team.
AB - In the award-winning memory services at Cumbria Partnership NHS Foundation Trust
in Carlisle, assistant practitioners are an essential part of the team.
PMID- 25138889
TI - Being washed by someone is therapeutic... and a treat.
AB - When in Istanbul, I visited a hamam, a traditional Turkish bath. I'm familiar
with other bathing rituals--steam room, sauna, Jacuzzi--but suspected being
washed by someone in front of others was not very British.
PMID- 25138890
TI - It is just a matter of application.
AB - The Camilla Cavendish review of support worker education was clear that improving
the quality of healthcare assistant (HCA) learning is central to delivering safe
and effective care. Well trained staff should treat patients well, so the point
of education and training must be to support HCAs to deliver effective care. But
how to guarantee this?
PMID- 25138891
TI - Going the extra mile for patients.
AB - Just 14 months after she changed career to become a healthcare assistant, Dot
O'Meara was presented with one of East Lancashire Hospitals NHS Trust's ten
unsung hero awards, writes Carol Davis, freelance journalist.
PMID- 25138892
TI - Addressing dehydration.
AB - Maintaining an adequate fluid intake is vital for health. Under normal
circumstnces, humans require about 2.5 litres of fluid per day. Dehydration
occurs when the body loses more fluid than it takes in, and can be the result of
either inadequate fluid intake or excessive fluid loss.
PMID- 25138893
TI - Legal advice. Richard Griffith on the Mental Capacity Act.
AB - Frequently, I am asked by healthcare assistants (HCAs) what the Mental Capacity
Act 2005 has to do with their practice as they are not concerned with formal
assessments of decision-making capacity or determinations of patients' best
interests.
PMID- 25138894
TI - Prevalence and characterization of small tympanic bone spicules and drumstick
like hyperostotic tympanic bone spicules in the middle ear cavity of dogs.
AB - Rounded, sessile, hyperattenuating structures detected in computed tomography
(CT) studies of canine tympanic bullae have been termed "otoliths." These have
been proposed to represent dystrophic mineralizations or heterotopic bone
formations in the middle ear that are potentially related to chronic otitis
media. Aims of the current study were to describe the prevalence, macroscopic,
and histological features of structures consistent with "otoliths" in the canine
tympanic cavity. Tympanic bullae from 50 routinely necropsied dogs and 139
retrospectively retrieved CT scans of canine clinical cases were examined. Small
tympanic bone spicules with pointed or clubbed tips essentially arising from the
free margin of the septum bullae were bilaterally present in the tympanic
cavities of all 50 of the necropsied dogs. In 48% of the dogs, "otolith"-like CT
detectable bone spicules carrying drumstick-like hyperostoses that were 1-6 mm in
diameter were also present. In the retrospective survey of bulla CT scans of 139
cases, the prevalence of hyperostotic tympanic bone spicules (HTBS) was 20%.
Findings from the current study indicated that the presence of small tympanic
bone spicules in adult dogs is most likely due to physiological bone growth in
the septum bullae and that HTBS represent osseous proliferations of small
tympanic bone spicules. However, the factors inducing formation of hyperostotic
spicules from small tympanic bone spicules remain unknown. The high prevalence of
HTBS displaying a similar appearance in bulla CT scans in dogs suggests that
these spicules should be included in a differential diagnosis list for
"otoliths."
PMID- 25138895
TI - Validation of the German version of the Clinical Assessment Interview for
Negative Symptoms (CAINS).
AB - Validated assessment instruments could contribute to a better understanding and
assessment of negative symptoms and advance treatment research. The aim of this
study was to examine the psychometric properties of a German version of the
Clinical Assessment Interview for Negative Symptoms (CAINS). In- and outpatients
(N=53) with schizophrenia or schizoaffective disorder were assessed with
standardized interviews and questionnaires on negative and positive symptoms and
general psychopathology in schizophrenia, depression, the ability to experience
anticipatory and consummatory pleasure, and global functioning. The results
indicated good psychometric properties, high internal consistency and promising
inter-rater agreement for the German version of the CAINS. The two-factor
solution of the original version of the CAINS was confirmed, indicating good
construct validity. Convergent validity was supported by significant correlations
between the CAINS subscales with the negative symptom scale of the Positive and
Negative Syndrome Scale, and with consummatory pleasure. The CAINS also exhibited
discriminant validity indicated by its non-significant correlations with positive
symptoms, general psychopathology and depression that are in line with the
findings for the original version of the CAINS. In addition, the CAINS correlated
moderately with global functioning. The German version of the CAINS appears to be
a valid and suitable diagnostic tool for measuring negative symptoms in
schizophrenia.
PMID- 25138896
TI - A phenomenological investigation of overvalued ideas and delusions in clinical
and subclinical anorexia nervosa.
AB - Anorexia Nervosa (AN) is an eating disorder characterised by distorted cognitions
about body weight and shape; but little is known about the phenomenological
characteristics of these beliefs. In this study, multidimensional and insight
based measurements were used to compare beliefs about body weight and shape in AN
to body image dissatisfaction in the general population, and delusional beliefs
in schizophrenia. Twenty participants with clinical and sub-clinical AN, 27
participants with schizophrenia and schizoaffective disorder, and 23 healthy
controls completed the Brown Assessment of Beliefs Scale and the Psychotic
Symptom Rating Scale in relation to a dominant belief regarding body weight/shape
(or body dissatisfaction in healthy controls) or a current delusion. All groups
completed the Peters Delusions Inventory to assess the prevalence of a range of
delusion-like beliefs. Participants with clinical and subclinical AN experienced
significantly higher preoccupation and distress for their belief in comparison to
both participants with schizophrenia/schizoaffective disorder rating a delusional
belief and the healthy controls rating a belief of body dissatisfaction. Both
clinical groups were comparable on ratings of belief conviction and disruption.
The data raise questions regarding the current frameworks that are used to
describe beliefs in AN.
PMID- 25138897
TI - Epidemiology of dengue in a high-income country: a case study in Queensland,
Australia.
AB - BACKGROUND: Australia is one of the few high-income countries where dengue
transmission regularly occurs. Dengue is a major health threat in North
Queensland (NQ), where the vector Aedes aegypti is present. Whether NQ should be
considered as a dengue endemic or epidemic region is an ongoing debate. To help
address this issue, we analysed the characteristics of locally-acquired (LA) and
imported dengue cases in NQ through time and space. We describe the epidemiology
of dengue in NQ from 1995 to 2011, to identify areas to target interventions. We
also investigated the timeliness of notification and identified high-risk areas.
METHODS: Data sets of notified cases and viraemic arrivals from overseas were
analysed. We developed a time series based on the LA cases and performed an
analysis to capture the relationship between incidence rate and demographic
factors. Spatial analysis was used to visualise incidence rates through space and
time. RESULTS: Between 1995 and 2011, 93.9% of reported dengue cases were LA,
mainly in the 'Cairns and Hinterland' district; 49.7% were males, and the mean
age was 38.0 years old. The sources of imported cases (6.1%) were Indonesia
(24.6%), Papua New Guinea (23.2%), Thailand (13.4%), East Timor (8.9%) and the
Philippines (6.7%), consistent with national data. Travellers importing dengue
were predominantly in the age groups 30-34 and 45-49 years old, whereas the age
range of patients who acquired dengue locally was larger. The number of LA cases
correlated with the number of viraemic importations. Duration of viraemia of
public health importance was positively correlated with the delay in
notification. Dengue incidence varied over the year and was typically highest in
summer and autumn. However, dengue activity has been reported in winter, and a
number of outbreaks resulted in transmission year-round. CONCLUSIONS: This study
emphasizes the importance of delay in notification and consequent duration of
viraemia of public health importance for dengue outbreak duration. It also
highlights the need for targeted vector control programmes and surveillance of
travellers at airports as well as regularly affected local areas. Given the
likely increase in dengue transmission with climate change, endemicity in NQ may
become a very real possibility.
PMID- 25138898
TI - Dynamics of bovine opsin bound to G-protein fragments.
AB - G protein-coupled receptors (GPCRs) are a large class of membrane proteins that
mediate communication of the cell with the outer environment. Upon activation by
an agonist, GPCRs undergo large-scale conformational changes that enable binding
of the G protein to the receptor. A key open question concerns the mechanism of
the long-distance coupling between the agonist-binding site and the cytoplasmic
site where G protein binds. Here we address this question by exploring the
molecular dynamics of bovine opsin bound to three different fragments of G
proteins. We find that an extended network of hydrogen bonds connects the agonist
retinal binding site to the G protein binding site via conserved amino acid
residues. The dynamics of the hydrogen-bonding network inside opsin couples to
interactions at the G protein binding site.
PMID- 25138899
TI - Survival trends among patients with advanced renal cell carcinoma in the United
States.
AB - INTRODUCTION: Since the approval of sorafenib in December 2005, several targeted
therapeutic agents have been approved by the FDA for the treatment of advanced
renal cell carcinoma (RCC). This study was conducted to find out whether the
improvements in survival of advanced RCC patients with targeted agents have
translated into a survival benefit in a population-based cohort. METHODS: We
analyzed the SEER 18 (Surveillance, Epidemiology and End RESULTS) registry
database to calculate the relative survival rates for advanced RCC patients
during 2001-2009, 2001-2005, 2006-2007 and 2008-2009. We also evaluated the
survival rates by age (<65 and >=65 years) and sex. RESULTS: The total number of
advanced RCC patients during 2001-2009, 2001-2005, 2006-2007 and 2008-2009 were
7,047, 4,059, 1,548 and 1,440, respectively. During 2001-2009, the 1- and 3-year
relative survival rates were 26.7+/-0.6 and 10.0+/-0.4%, respectively. There was
no significant difference in 1-year relative survival rates for patients
diagnosed during 2006-2007 and 2008-2009 compared to those diagnosed during 2001
2005. Similarly, the 3-year survival rates for patients diagnosed during 2006
2007 were similar to those diagnosed during 2001-2005. CONCLUSIONS: This
population-based study showed that there was no significant improvement in
relative survival rates among advanced RCC patients in the era of targeted
agents.
PMID- 25138900
TI - Current opinion on optimal systemic treatment for metastatic colorectal cancer:
outcome of the ACTG/AGITG expert meeting ECCO 2013.
AB - The treatment of metastatic colorectal cancer has evolved greatly in the last 15
years, involving combined chemotherapy protocols and, in more recent times, new
biologic agents. Clinical benefit from the use of targeted therapy with
bevacizumab, aflibercept, cetuximab, panitumumab and regorafenib in the treatment
of metastatic colorectal cancer is now well established with median overall
survival accepted as over 24 months, and with super selection for extended RAS
patients higher again. The optimal timing of treatment options requires careful
consideration of predictive biomarkers, and importantly the potential for
interactions, to derive the maximal benefit. A group of colorectal subspecialty
medical oncologists from Australia, the USA, the Netherlands and Germany met
during ECCO 2013 to discuss current practice. Subsequent new data from the
American Society of Clinical Oncology were also reviewed. This article reviews
the evidence discussed in support of modern treatments for colorectal cancer and
the decision-making behind the treatment choices, with their benefits and risks.
PMID- 25138901
TI - Effect of omeprazole dose, nonsteroidal anti-inflammatory agents, and smoking on
repair mechanisms in acute peptic ulcer bleeding.
AB - BACKGROUND: Peptic ulcer bleeding (PUB) is a major cause of upper
gastrointestinal bleeding. The effect of omeprazole on mucosal repair is unknown.
AIMS: We studied the effect of omeprazole, nonsteroidal anti-inflammatory agents,
and smoking on PUB. METHODS: There were 43 PUB patients who received regular or
high dose of omeprazole for 72 h. Biopsies from antrum and corpus were taken
before and after treatment. Biopsy samples from 20 celiac disease patients worked
as controls. The expression of Ki-67, Bcl-2, COX-2, Hsp27, and Hsp70 was analyzed
from patients and controls. RESULTS: Bcl-2 expression in PUB patients was lower
than in controls. However, Bcl-2 increased significantly from 5.0 (SD 4.5) to 9.1
% (SD 6.7), p = 0.0004, in the antrum after omeprazole. In univariate analysis, a
high omeprazole dose caused a more profound increase in Ki-67 expression in the
corpus: 35.3 % (SD 54.8) than a regular dose: -10.1 % (SD 40.6), p = 0.022. In
multivariate analysis, Ki-67 decreased significantly in the corpus between the
pre- and posttreatment period (p = 0.011), while a high omeprazole dose (p =
0.0265), the use of NSAIDs (p = 0.0208), and smoking (p = 0.0296) significantly
increased Ki-67 expression. Bcl-2 in the corpus increased significantly (p =
0.0003) after treatment. CONCLUSIONS: Our findings suggest that Bcl-2 may be an
important factor in the pathogenesis of a peptic ulcer and PUB. In addition, high
dose omeprazole increased the expression of Ki-67, which may enhance the healing
process of a peptic ulcer.
PMID- 25138902
TI - Endoclips to facilitate cannulation and sphincterotomy during ERCP in a patient
with an ampulla within a large duodenal diverticulum: case report and literature
review.
PMID- 25138903
TI - Acute fatty liver of pregnancy treated with plasma exchange.
PMID- 25138904
TI - Non-MalIg(G4)nant Biliary Obstruction: When the Pill Is Mightier than the Knife.
PMID- 25138905
TI - More with less: pancreas-preserving total duodenectomy.
PMID- 25138906
TI - Public supply well vulnerability.
PMID- 25138907
TI - Cyantraniliprole: a valuable tool for Frankliniella occidentalis (Pergande)
management.
AB - BACKGROUND: Frankliniella occidentalis is a worldwide economically important
pest. Scarcity of effective products and cross-resistance issues make resistance
to existing insecticides a recurring problem that requires the development of new
control tools, such as incorporating novel compounds. Lethal effects of
cyantraniliprole on adults and larvae from field and insecticide-resistant
populations were evaluated. In addition, the sublethal effects on biological
features such as fecundity, fertility, feeding, oviposition and mating were
studied. RESULTS: Results obtained for larvae produced LC50 values ranging from
33.4 to 109.2 mg L(-1) , with a low natural variability (3.3-fold) and a LC50
composite value of 52.2 mg L(-1) . The susceptibility for adults was 23-fold
lower than for larvae. No evidence of cross-resistance between cyantraniliprole
and established insecticides used against thrips was evident. Relevant sublethal
effects of cyantraniliprole were demonstrated, including reduced fecundity,
fertility, feeding, oviposition and mating success. CONCLUSION: Low variation in
susceptibility across contemporary populations of F. occidentalis and a lack of
cross-resistance to other insecticides indicate that cyantraniliprole is a
potential candidate in rotation programmes within an insecticide resistance
management strategy. The combined sublethal effect on reproduction will have an
important impact on population reduction. Available data indicate that
cyantraniliprole is likely to be a valuable tool for managing thrips populations.
PMID- 25138909
TI - China's 50% caesarean delivery rate: is it too high?
PMID- 25138908
TI - MG428 is a novel positive regulator of recombination that triggers mgpB and mgpC
gene variation in Mycoplasma genitalium.
AB - The human pathogen Mycoplasma genitalium employs homologous recombination to
generate antigenic diversity in the immunodominant MgpB and MgpC proteins. Only
recently, some of the molecular factors involved in this process have been
characterized, but nothing is known about its regulation. Here, we show that M.
genitalium expresses N-terminally truncated RecA isoforms via alternative
translation initiation, but only the full-length protein is essential for gene
variation. We also demonstrate that overexpression of MG428 positively regulates
the expression of recombination genes, including recA, ruvA, ruvB and ORF2, a
gene of unknown function co-transcribed with ruvAB. The co-ordinated induction of
these genes correlated with an increase of mgpBC gene variation. In contrast,
cells lacking MG428 were unable to generate variants despite expressing normal
levels of RecA. Similarly, deletion analyses of the recA upstream region defined
sequences required for gene variation without abolishing RecA expression. The
requirement of these sequences is consistent with the presence of promoter
elements associated with MG428-dependent recA induction. Sequences upstream of
recA also influence the relative abundance of RecA isoforms, possibly through
translational regulation. Overall, these results suggest that MG428 is a positive
regulator of recombination and that precise control of recA expression is
required to initiate mgpBC variation.
PMID- 25138910
TI - Attentional load interferes with target localization across saccades.
AB - The retinal positions of objects in the world change with each eye movement, but
we seem to have little trouble keeping track of spatial information from one
fixation to the next. We examined the role of attention in trans-saccadic
localization by asking participants to localize targets while performing an
attentionally demanding secondary task. In the first experiment, attentional load
decreased localization precision for a remembered target, but only when a saccade
intervened between target presentation and report. We then repeated the
experiment and included a salient landmark that shifted on half the trials. The
shifting landmark had a larger effect on localization under high load, indicating
that observers rely more on landmarks to make localization judgments under high
than under low attentional load. The results suggest that attention facilitates
trans-saccadic localization judgments based on spatial updating of gaze-centered
coordinates when visual landmarks are not available. The availability of reliable
landmarks (present in most natural circumstances) can compensate for the effects
of scarce attentional resources on trans-saccadic localization.
PMID- 25138911
TI - Object ownership and action: the influence of social context and choice on the
physical manipulation of personal property.
AB - Understanding who owns what is important for guiding appropriate action in a
social context. Previously, we demonstrated that ownership influences our
kinematic patterns associated with hand-object interactions (Constable et al. in
Cognition 119(3):430-437, 2011). Here, we present a series of experiments aimed
at determining the underlying mechanisms associated with this effect. We asked
participants to lift mugs that differed in terms of ownership status (Experiments
1 and 2) and personal preference (Experiment 3) while recording spatial and
acceleration measures. In Experiment 1, participants lifted their own mug with
greater acceleration and drew it closer to themselves than they did the
experimenter's mug. They also lifted the experimenter's mug further to the right
compared with other mugs. In Experiment 2, spatial trajectory effects were
preserved, but the acceleration effect abolished, when the owner of the 'other
owned' mug was a known-but absent-confederate. Experiment 3 demonstrated that
merely choosing to use a mug was not sufficient to elicit rightward drift or
acceleration effects. We suggest that these findings reflect separate and
distinct mechanisms associated with socially related visuomotor processing.
PMID- 25138912
TI - Vestibular evoked potentials (VsEPs) of cortical origin produced by impulsive
acceleration applied at the nasion.
AB - We report the results of a study to record vestibular evoked potentials (VsEPs)
of cortical origin produced by impulsive acceleration (IA). In a sample of 12
healthy participants, evoked potentials recorded by 70 channel
electroencephalography were obtained by IA stimulation at the nasion and compared
with evoked potentials from the same stimulus applied to the forefingers. The
nasion stimulation gave rise to a series of positive and negative deflections in
the latency range of 26-72 ms, which were dependent on the polarity of the
applied IA. In contrast, evoked potentials from the fingers were characterised by
a single N50/P50 deflection at about 50 ms and were polarity invariant. Source
analysis confirmed that the finger evoked potentials were somatosensory in
origin, i.e. were somatosensory evoked potentials, and suggested that the nasion
evoked potentials plausibly included vestibular midline and frontal sources, as
well as contributions from the eyes, and thus were likely VsEPs. These results
show considerable promise as a new method for assessment of the central
vestibular system by means of VsEPs produced by IA applied to the head.
PMID- 25138913
TI - Revisiting the association between hypnotisability and blink rate.
AB - Blink rate (BR), which is considered an index of the dopaminergic tone, has been
studied in 41 subjects with high (highs), medium (mediums) and low (lows)
hypnotisability scores in resting conditions. It has been found higher in highs;
relaxation (indicated by skin conductance), anxiety and the proneness to
absorption in tasks (assessed by questionnaires) were not responsible for the
observed difference. In contrast, the BR difference did not survive controlling
for mind wandering (MW questionnaire) whose variability could account for
contrasting earlier reports, although no significant hypnotisability-related
difference has been observed in MW scores. Findings do not allow to exclude that
mechanisms other than dopaminergic ones may be involved in the observed
difference in BR. In particular, we suggest that one of the mechanisms possibly
sustaining the highs' higher BR may be a reduced cerebellar inhibition. In fact,
cerebellar impairment is associated with higher BR and several studies of
sensorimotor integration indicate different cerebellar controls in the highs' and
lows' behavior.
PMID- 25138914
TI - Sodium-assisted formation of binding and traverse conformations of the substrate
in a neurotransmitter sodium symporter model.
AB - Therapeutics designed to increase synaptic neurotransmitter levels by inhibiting
neurotransmitter sodium symporters (NSSs) classify a strategic approach to treat
brain disorders such as depression or epilepsy, however, the critical elementary
steps that couple downhill flux of sodium to uphill transport of neurotransmitter
are not distinguished as yet. Here we present modelling of NSS member neuronal
GAT1 with the substrate γ-aminobutyric acid (GABA), the major inhibitory
neurotransmitter. GABA binding is simulated with the occluded conformation of
GAT1 homodimer in an explicit lipid/water environment. Simulations performed in
the 1-10 ns range of time elucidated persistent formation of halfextended minor
and H-bridged major GABA conformations, referred to as binding and traverse
conformations, respectively. The traverse GABA conformation was further
stabilized by GAT1-bound Na(+)(1). We also observed Na(+)(1) translocation to
GAT1-bound Cl(-) as well as the appearance of water molecules at GABA and GAT1
bound Na(+)(2), conjecturing causality. Scaling dynamics suggest that the
traverse GABA conformation may be valid for developing substrate inhibitors with
high efficacy. The potential for this finding is significant with impact not only
in pharmacology but wherever understanding of the mechanism of neurotransmitter
uptake is valuable.
PMID- 25138915
TI - Feasibility study of a new RF coil design for prostate MRI.
AB - The combined use of a torso-pelvic RF array coil and endorectal RF coil is the
current state-of-the-art in prostate MRI. The endorectal coil provides high
detection sensitivity to acquire high-spatial resolution images and spectroscopic
data, while the torso-pelvic coil provides large coverage to assess pelvic lymph
nodes and pelvic bones for metastatic disease. However, the use of an endorectal
coil is an invasive procedure that presents difficulties for both patients and
technicians. In this study, we propose a novel non-invasive RF coil design that
can provide both image signal to noise ratio and field of view coverage
comparable to the combined torso-pelvic and endorectal coil configuration. A
prototype coil was constructed and tested using a pelvic phantom. The results
demonstrate that this new design is a viable alternative for prostate MRI.
PMID- 25138918
TI - Fingolimod in active multiple sclerosis: an impressive decrease in Gd-enhancing
lesions.
AB - BACKGROUND: Fingolimod is a disease modifying therapy (DMT) in highly active
relapsing remitting multiple sclerosis (RRMS), as is natalizumab. Fingolimod
decreases annual relapse rates and gadolinium enhancing lesions on MRI as
compared to either interferon beta (IFNbeta) or placebo. The effect of fingolimod
on MRI outcomes compared to natalizumab treatment has not been investigated in
(head to head) clinical trials. Clinical experience with natalizumab is much more
extended and in general practice often preferred. CASE PRESENTATION: This case
describes a 31-year old woman with RRMS, who experienced severe side effects on
natalizumab. After a voluntary four months treatment free period, a severe
relapse appeared which was treated with prednisone and plasmapheresis; thereafter
fingolimod was initiated. In the following months MRI signs improved
spectacularly. CONCLUSION: This case suggests that fingolimod might be a good
alternative for natalizumab, especially for use in RRMS patients, with highly
active, advanced disease, when natalizumab treatment is stopped due to side
effects or even after a severe relapse.
PMID- 25138919
TI - NMR of solutes in nematic and smectic A liquid crystals: the anisotropic
intermolecular potential.
AB - Orientational order parameters determined from (1)H NMR spectroscopy of solutes
in liquid crystals that form both nematic and smectic A phases are used to
determine the solute smectic A order parameters and the smectic-nematic coupling
term. For the analysis, it is necessary to know the nematic part of the potential
in the smectic A phase: various ways of extrapolating parameters from the nematic
phase to the smectic phase are explored.
PMID- 25138917
TI - Maternal age and serum concentration of human chorionic gonadotropin in early
pregnancy.
AB - OBJECTIVE: To study whether maternal age is associated with serum concentration
of human chorionic gonadotropin in early pregnancy. DESIGN: Cross-sectional
study. SETTING: Oslo University Hospital in Oslo, Norway. POPULATION: All vital
pregnancies in gestational week 8 conceived by in vitro fertilization between
February 1996 and February 2013 (n = 4472). METHODS: Serum concentrations of
human chorionic gonadotropin were measured on day 12 after embryo transfer/day 16
following ovulation induction. Trends in geometric means of human chorionic
gonadotropin concentrations by maternal age group were tested by linear
regression analysis. We also studied the association of maternal age (years) with
log-transformed human chorionic gonadotropin concentrations, and adjustments were
made for number of embryos transferred, method of in vitro fertilization and year
(period) of embryo transfer. MAIN OUTCOME MEASURE: Serum concentration of human
chorionic gonadotropin. RESULTS: Geometric mean concentrations of human chorionic
gonadotropin decreased with increasing maternal age (p = 0.024, test for trend by
weighted linear regression). Also, we estimated a significant negative
association of maternal age with log-transformed human chorionic gonadotropin
concentrations (adjusted regression coefficient -0.011, standard error 0.003, p <
0.001). CONCLUSIONS: Serum concentrations of human chorionic gonadotropin in very
early pregnancy decreased with maternal age. Since human chorionic gonadotropin
is synthesized in trophoblast cells only, the lower human chorionic gonadotropin
concentrations in women of advanced age may reflect functional impairment or
delayed proliferation of trophoblast cells in early pregnancy in these women.
PMID- 25138920
TI - Contending with uncertainty in conservation management decisions.
AB - Efficient conservation management is particularly important because current
spending is estimated to be insufficient to conserve the world's biodiversity.
However, efficient management is confounded by uncertainty that pervades
conservation management decisions. Uncertainties exist in objectives, dynamics of
systems, the set of management options available, the influence of these
management options, and the constraints on these options. Probabilistic and
nonprobabilistic quantitative methods can help contend with these uncertainties.
The vast majority of these account for known epistemic uncertainties, with
methods optimizing the expected performance or finding solutions that achieve
minimum performance requirements. Ignorance and indeterminacy continue to
confound environmental management problems. While quantitative methods to account
for uncertainty must aid decisions if the underlying models are sufficient
approximations of reality, whether such models are sufficiently accurate has not
yet been examined.
PMID- 25138922
TI - Enabling LiTFSI-based electrolytes for safer lithium-ion batteries by using
linear fluorinated carbonates as (Co)solvent.
AB - In this Full Paper we show that the use of lithium
bis(trifluoromethanesulfonyl)imide (LiTFSI) as conducting salt in commercial
lithium-ion batteries is made possible by introducing fluorinated linear
carbonates as electrolyte (co)solvents. Electrolyte compositions based on LiTFSI
and fluorinated carbonates were characterized regarding their ionic conductivity
and electrochemical stability towards oxidation and with respect to their ability
to form a protective film of aluminum fluoride on the aluminum surface. Moreover,
the investigation of the electrochemical performance of standard lithium-ion
anodes (graphite) and cathodes (Li[Ni1/3 Mn1/3 Co1/3 ]O2 , NMC) in half-cell
configuration showed stable cycle life and good rate capability. Finally, an
NMC/graphite full-cell confirmed the suitability of such electrolyte compositions
for practical lithium-ion cells, thus enabling the complete replacement of LiPF6
and allowing the realization of substantially safer lithium-ion batteries.
PMID- 25138923
TI - Characterisation of whisker control in the California sea lion (Zalophus
californianus) during a complex, dynamic sensorimotor task.
AB - Studies in pinniped whisker use have shown that their whiskers are extremely
sensitive to tactile and hydrodynamic signals. While pinnipeds position their
whiskers on to objects and have some control over their whisker protractions, it
has always been thought that head movements are more responsible for whisker
positioning than the movement of the whiskers themselves. This study uses ball
balancing, a dynamic sensorimotor skill that is often used in human and robotic
coordination studies, to promote sea lion whisker movements during the task. For
the first time, using tracked video footage, we show that sea lion whisker
movements respond quickly (26.70 ms) and mirror the movement of the ball, much
more so than the head. We show that whisker asymmetry and spread are both altered
to help sense and control the ball during balancing. We believe that by designing
more dynamic sensorimotor tasks we can start to characterise the active nature of
this specialised sensory system in pinnipeds.
PMID- 25138924
TI - B chromosomes in the grasshopper Eyprepocnemis plorans are present in all body
parts analyzed and show extensive variation for rDNA copy number.
AB - B chromosomes in the grasshopper Eyprepocnemis plorans are considered to be
mitotically stable, because all meiotic (primary spermatocytes and oocytes) or
mitotic (embryos, ovarioles, and gastric caecum) cells analyzed within the same
individual show the same B chromosome number. Nothing is known, however, about
body parts with somatic tissues with no mitotic activity in adult individuals,
constituting the immense majority of their body. Therefore, we investigated
whether B chromosomes are present in 8 non-mitotically active somatic body parts
from both sexes in addition to ovarioles and testes by PCR analysis of 2 B
specific molecular markers. We also elucidated the number of B chromosomes that
an individual carried through quantifying the B-located rDNA copy number by qPCR.
Our results indicated the amplification of both B-specific markers in all
analyzed body parts. However, we found high variation between males for the
estimated number of rDNA units in the B chromosomes. These results demonstrate
the presence of B chromosomes in all body parts from the same individual and
suggest a high variation in the rDNA content of the B chromosomes carried by
different individuals from the same population, presumably due to unequal
crossovers during meiosis.
PMID- 25138926
TI - [Echocardiography].
AB - Assessment of ischemic mitral regurgitation( IMR) severity is important to
stratify patients' management. Because IMR is influenced by loading condition
seriously, it is difficult to evaluate severity of IMR in clinically stable
condition at rest. Exercise stress echocardiography is useful tool to assess
"true" severity of IMR. Recently, mitral valve plasty( undersized annuloplasty)
creates a new problem, which is called "functional mitral stenosis". Exercise
stress echocardiography also reveals this hemodynamics. Recent 3-dimensional (3D)
echocardiography enables an intuitive understanding a valve anatomy by surgeon's
view, and a more detailed quantitative evaluation. The 3D echocardiography can
contribute to exact valve area calculation and can evaluate the forms of the
valve ring which had difficulty in evaluation by 2D echocardiography. The
treatment of structural heart disease with catheter has been introduced, and
therefore the importance of the 3D echocardiography increases in this field. In
this review, we describe the role of stress echocardiography on the assessment of
IMR and the current status of 3D echocardiography.
PMID- 25138927
TI - [Role of cardiac computed tomography in cardiac surgery].
AB - In the field of cardiovascular surgery, cardiac computed tomography (CT) has
served an important role in association with the improvement of the spatial and
temporal resolution. Because CT angiography (CTA) provides more available
information than plain CT, CTA has been increasingly used to access the coronary
arteries and graft patency after coronary artery bypass grafting (CABG).
Recently, minimally invasive cardiac surgeries, including CABG with left mini
thoracotomy and mitral valve surgery with right mini-thoracotomy, are revived,
which requires preoperative CTA to make a strategy of incision placement on the
basis of anatomical relationship between the target structure of the heart and
the thorax. In Japan, transcatheter aortic valve implantation (TAVI) was approved
in the late 2013, and is expected to be widely performed in the future. CTA is
extremely useful for TAVI patients to determine the choice of the valve size and
the surgical approach. CT provides many other valuable findings to us, but if we
cannot fully leverage it in the daily cardiovascular surgery, its value is
decreased. We have to acquire enough skill to maximize the performance of CT in
the practical clinical setting.
PMID- 25138928
TI - [Cardiovascular magnetic resonance imaging].
AB - Cardiac magnetic resonance imaging (CMR) evolves and is occupying an important
status in cardiovascular diagnostic imaging. In particular, in the estimation of
the cause of heart failure, or evaluation of severity-of-illness and prognostic
presumption, utility is high clinically. In this chapter, about a selection
sequence for taking image according to the purpose, description of findings, and
its clinical utility are introduced. And the role which this imaging plays will
be discussed in the near future.
PMID- 25138930
TI - [Evoked potentials monitoring in aortic surgery].
AB - Somatosensory evoked potential (SSEP), evoked spinal cord potential (ESCP) and
motor evoked potential (MEP) have been used to detect spinal cord ischemia during
aortic surgery. SSEP evaluates the sensory pathway, and is recorded from the
sensory cortex by peripheral nerve stimulation. The interval from the onset of
ischemia to change is relatively long(5-10 minutes). It has less frequently been
used because of the high false negative and false positive rate. ESCP is recorded
from the spinal cord by direct stimulation of the cord. It reflects the function
of spinal tract but not that of alpha motor neurons. It is resistant to
anesthesia and both the sensitivity and specificity is high, but the interval
from ischemia to change is relatively long. Together with the necessity of 2
epidural electrodes, its application in aortic surgery has become infrequent.
Since the introduction of train pulse transcranial electrical stimulation,
myogenic MEP have gained widespread acceptance. It evaluates motor pathways from
the cortex to the muscle, and therefore is influenced by non-spinal factors such
as peripheral nerve ischemia. Its vulnerability to anesthesia requires special
anesthetic consideration, and baseline amplitude fluctuation is common. It is
highly sensitive and shows changes in the early phase of spinal cord ischemia.
PMID- 25138929
TI - [Cerebral blood flow monitoring].
AB - Cerebral ischemic events remain a major problem in patients undergoing cardiac
and thoracic aortic surgery. Efforts to improve outcomes have been made in many
aspects which include cerebral monitoring. New technology is making it possible
to shed a light to the brain, which historically used to be a black box during
general anesthesia in the operating room. Cerebral brain monitoring methods
include cerebral oxymetry using near infrared spectroscopy, trans cranial
Doppler, Jugular venous oxygen saturation, bispectral index, temporal artery
pressure monitoring. Cerebral oxymetry probably is the most commonly used method
among these based on its simplicity and reproducibility. Though it is easy to
obtain numbers from cerebral oxymetry, it is important to understand the
principle and the limitations to interpret the results, properly.
PMID- 25138931
TI - [How to use assist devices effectively in off-pump coronary artery bypass
surgery].
AB - Off-pump coronary artery bypass is a technically demanding procedure, which is,
however, widely performed in Japan. In this paper, most widely used assist
devices such as tissue stabilizers, heart positioners, intraluminal coronary
artery shunts and proximal anastomosis assist devices are introduced along with
tips of usage.
PMID- 25138932
TI - [Overview of ablation devices for atrial fibrillation surgery].
AB - Since Cox-maze procedure was first reported in 1987, ablation technology has made
great progress and revolutionized atrial fibrillation surgery. Various energy
sources have been introduced to facilitate creating conduction block within the
atria. These sources include radiofrequency, cryothermia, microwave, laser, and
high-frequency focused ultrasound( HIFU). They have been utilized both
endocardially in the arrested heart and epicardially in the beating heart. The
goal of all these sources is to create transmural lesions which enable
irreversible conduction block. They have been reported to have clinical efficacy,
but each of them have their own advantages and disadvantages, and their ability
of creating transmural lesions are also different. It is important for surgeons
that they fully understand these differences to make appropriate use of these
technologies for achieving safe atrial fibrillation surgery and developing less
invasive new procedures.
PMID- 25138933
TI - [Intraaortic balloon pumping( IABP) in Japan].
AB - The intraaortic balloon pumping (IABP) is the most widely used circulatory assist
device. IABP increases coronary perfusion in diastolic phase by the inflation of
the balloon in the descending aorta (diastolic augmentation) and reduces
afterload in systolic phase by the deflation of the balloon( systolic unloading).
IABP improves the hemodynamic condition of patients who fall into acute heart
failure and/or cardiogenic shock. Six-type IABP system can be used in Japan. The
IABP-SHOCK II trial shows that there is no significant difference in mortality
between optimal medical treatment with IABP and without IABP in addition to early
revascularization. Clinical backgrounds in Japan are different from those in IABP
SHOCK II trial, and the further prospective studies of IABP in Japan thus called
for.
PMID- 25138934
TI - [Fundamental features on percutaneous cardiopulmonary support].
AB - The fundamental features on percutaneous cardiopulmonary support (PCPS) were
reviewed. The number of PCPS installation in Japan has been increasing especially
in the area of emergency medicine and cardiology. All-in-one package for PCPS
system is becoming a mainstream in clinical practice. It is considered to be
crucial to understand the details in characteristics and pitfalls on respective
products. The results of nation-wide questionnaire indicate that the detailed
criteria for PCPS usage in clinical practice appear to be variable among
facilities in Japan;therefore, the formulation of guideline and educational
system for PCPS installation is required.
PMID- 25138935
TI - [Implantable ventricular assist device].
AB - Implantable ventricular assist device( VAD) is the only evidence-based option to
treat stage D heart failure patients with significant symptoms at rest in spite
of maximum medical therapy, other than heart transplant. Implantable VADs
available in Japan include Evaheart, DuraHeart both from Japan, Jarvik 2000 and
HeartMate II both from United States. In Japanese settings, implantable VAD is
indicated and insured only for patients who are supposed to have an indication
for receiving heart transplant, which means "bridge to transplantation" use. And
in Japan, implantable VAD can be implanted for patients less than 65 years old if
it needs to be insured. In the University of Tokyo Hospital, the mid-term
outcomes of 41 implantable VAD patients were acceptable with 2 hospital deaths, 2
remote deaths and one year survival rate at 88%.Considering the present Japanese
situation with extreme shortage of organ donation, the extended application of
implantable VADs as "Destination Therapy" is awaited, but quality of life of care
givers as well as patients themselves and sustainable follow-up system provided
by healthcare professionals need to be warranted.
PMID- 25138937
TI - [Thoracic endovascular aneurysm repair].
AB - Endovascular aneurysm repair has brought revolution in the treatment of aortic
disease. Although surgical treatment for thoracic aortic aneurysm impose large
invasiveness on patients of aged population, endovascular aneurysm repair supply
extreme less-invasive treatment for patients with thoracic aortic disease,
because of unnecessary for thoracotomy and extracorporeal circulation. Thoracic
endovascular aneurysm repair will have further applications and distributions
with development and improvement of the device.
PMID- 25138936
TI - [Annuloplasty ring and band for valve repair].
AB - Annulus dilatation is present in almost all patients with mitral regurgitation,
tricuspid regurgitation. Therefore annuloplasty is required to obtain normal
leaflet coaptation. Annuloplasty ring or band offers more stability in valve
repair, improving long-term outcome. Since annuloplasty ring and band of various
types can be used, to understand the characteristics and to select proper size
are important.
PMID- 25138938
TI - [Transcatheter aortic valve replacement].
AB - While transcatheter aortic valve replacement( TAVR) has spread rapidly all over
the world for highrisk patients with severe aortic stenosis (AS), SAPIEN XT was
approved in Japan in October 2013. Since that, approximately 400 TAVR cases were
performed in Japan. In our institute, we have performed 164 cases since first
case in Japan in 2009 and have achieved satisfactory early results(30-day
mortality:1.2%). At the same time, however, simultaneously various TAVR-related
complications including a paravalvular leak, stroke, vascular complications, and
coronary obstruction were observed. A reduction in the incidence and severity of
these complications had led technical improvements in various new devices(2nd
generation TAVR device such as the SAPIEN 3, ACURATE, and JenaValve) and in
implantation techniques including repositioning/recapturing features,
paravalvular sealing technologies, and prevention of coronary obstruction.
Furthermore, there is also increasing experience with special indications for
TAVR such as pure aortic valve insufficiency or valve-in-valve techniques.
Currently, an increasing number of publications of midterm results demonstrate
good prosthetic valve function and durability, with good quality of life and low
morbidity after TAVR. There are also some randomized trials such as PARTNER 2 or
SURTAVI to investigate potential benefits of TAVR for intermediate-risk patients.
These improvements in the TAVR devices promises the expansion of TAVR towards the
treatment of lower-risk patients in the near future.
PMID- 25138939
TI - [da Vinci surgical system].
AB - The da Vinci surgical system was developed by Intuitive Surgical Inc. in the
United States as an endoscopic surgical device to assist remote control
surgeries. In 1998, the Da Vinci system was first used for cardiothoracic
procedures. Currently a combination of robot-assisted internal thoracic artery
harvest together with coronary artery bypass grafting (CABG) through a mini
incision (ThoraCAB) or totally endoscopic procedures including anastomoses under
robotic assistance (TECAB) are being conducted for the treatment of coronary
artery diseases. With the recent advances in catheter interventions, hybrid
procedures combining catheter intervention with ThoraCAB or TECAB are anticipated
in the future.On the other hand, with the decrease in number of coronary artery
bypass surgeries, the share of valvular surgeries is expected to increase in the
future. Among them, mitral valvuloplasty for mitral regurgitation is anticipated
to be conducted mainly by low-invasive procedures, represented by minimally
invasive cardiac surgery( MICS) and robot-assisted surgery. Apart from the
intrinsic good surgical view, robotic-assisted systems offer additional
advantages of the availability of an amplified view and the easy to observe the
mitral valve in the physiological position. Thus, robotic surgical surgeries that
make complicated procedures easier are expected to accomplish further
developments in the future. Furthermore, while the number of surgeries for atrial
septal defects has decreased dramatically following the widespread use of
Amplatzer septal occluder, robotic surgery may become a good indication for cases
in which the Amplatzer device is not indicated. In Japan, clinical trial of the
da Vinci robotic system for heart surgeries has been completed. Statutory
approval of the da Vinci system for mitral regurgitation and atrial septal
defects is anticipated in the next few years.
PMID- 25138940
TI - [Percutaneous edge-to-edge repair using the MitraClip system].
AB - Percutaneous edge-to-edge repair with the MitraClip system has emerged as a new
therapeutic option for moderate to severe or severe mitral regurgitation (MR).
Several clinical studies demonstrated its safety and efficacy in patients with
both degenerative and functional MR. Based on these results, this catheter-based
therapy received CE mark for both etiologies of MR in 2008, and approval from
United States (US) Food and Drug Administration for degenerative MR with
prohibited surgical risk in 2013. To date, around 12,000 patients underwent the
MitraClip therapy worldwide. In the present review article, we describe the
concept and procedural steps of the MitraClip therapy, results of major clinical
trials, and current status in US.
PMID- 25138941
TI - [Application of medical imaging to general thoracic surgery].
AB - Medical imaging technology is rapidly progressing. Positron emission tomography
(PET) has played major role in the staging and choice of treatment modality in
lung cancer patients. Magnetic resonance imaging (MRI) is now routinely used for
mediastinal tumors and the use of diffusion-weighted images (DWI) may help in the
diagnosis of malignancies including lung cancers. The benefits of medical imaging
technology are not limited to diagnostics, and include simulation or navigation
for complex lung resection and other procedures. Multidetector row computed
tomography (MDCT) shortens imaging time to obtain detailed and precise volume
data, which improves diagnosis of small-sized lung cancers. 3-dimensional
reconstruction of the volume data allows the safe performance of thoracoscopic
surgery. For lung lobectomy, identification of the branching structures,
diameter, and length of the arteries is useful in selecting the procedure for
blood vessel treatment. For lung segmentectomy, visualization of venous branches
in the affected segments and intersegmental veins has facilitated the
preoperative determination of the anatomical intersegmental plane. Therefore, the
application of medical imaging technology is useful in general thoracic surgery.
PMID- 25138942
TI - [Diagnostic bronchoscopy].
AB - Endoscopic technology has developed markedly with endobronchial ultrasonography
(EBUS) having become dramatically widespread over the past 10 years. EBUS-guided
transbronchial needle aspiration (EBUS-TBNA) has become an important modality for
the mediastinal staging of lung cancer as well as mediastinoscopy. The
combination of EBUS with a guide sheath( EBUS-GS) and virtual navigation systems,
such as Bf-NAVI, LungPoint, superDimension/Bronchus system, is useful for
diagnosis of small peripheral pulmonary lesions. Moreover, the ability to observe
lesions has increased using picture enhancement developed by new methods such as
autofluorescence imaging( AFI), narrow band imaging (NBI), and FUJI intelligent
color enhancement( FICE). However, these modalities have limited value in
detection of lung cancer and preneoplastic lesions. In recent years, the
indications for AFI have widened and it can be now used for evaluation of tumor
extension. Knowledge of these new technologies is certainly useful to allow their
routine clinical use by respiratory surgeons. We will review these new
technologies in this paper.
PMID- 25138943
TI - [Present status of interventional pulmonology].
AB - Endobronchial intervention has been well established in therapeutic and
palliative methods for patients with malignant and benign airway obstruction.
Central airway tumor obstruction could lead to significant dyspnea or hemoptysis
and dramatically lower the quality of life. Such symptoms can be relieved
immediately via bronchoscopic intervention. Endobronchial therapies such as
neodymium yttrium aluminum garnet( Nd:YAG) laser therapy, argon plasma
coagulation and microwave coagulation or stent placement are well-established
treatment options. Each of these modalities has its specific advantages and
disadvantages. Laser therapy is direct thermal ablation applied to endobronchial
tumors. It has sufficient power to vaporize tissues and produces an excellent
coagulation effect. However, the risk of perforation is high. On the other hand,
photodynamic therapy has the curative potential for patients with early
superficial lung cancer using low power laser. Moreover, it has recently been
approved for the treatment of other cancers including advanced lung cancer. Stent
placement is an effective treatment to re-establish airway patency and
immediately relieve the patient from life-threatening dyspnea. Stent restenosis,
migration, mucus plug and hemoptysis are common short-term and longterm problems.
It is important to select the appropriate treatment method for each patient to
avoid complications and achieve successful results.
PMID- 25138944
TI - [Thoracoscope for thoracoscopic surgery].
AB - Thoracoscope is very important in thoracoscopic surgery (TS). There are many
types of telescope and monitor. Also the placement of access port and location of
the monitor image often differ between each institutions. Thoracic surgeons need
to know these features to perform good TS. In our department, 2,375 patients (98%
of all operation) were underwent 3-ports TS for 5 years. Operator always stands
by patient's right side and camera assistant stands by patient's left side. Using
2 monitors, left side of monitors image sets to patient's head side and camera
assistant see the inverted image monitor. Regardless of the localization of the
lesion, three ports are always placed in same intercostal space. One of the
advantages of TS is the ability of obtaining close and magnified operative image
which can be possible to be shared with assistant and other surgical staff. The
other advantages is that surgeons can review the recorded surgical digital
versatile disc(DVD).
PMID- 25138945
TI - [Characteristics of customized device for video-assisted thoracoscopic surgery].
AB - Video-assisted thoracoscopic surgery (VATS) has been a mainstay in surgical
interventions for an early staged lung cancer over a decade. VATS procedures are
nowadays categorized into 2 groups. One is a modified open procedures through a
mini-thoracotomy with customization of conventional instruments. The other is a
port-access procedure with use of newly developed instruments for endoscopic
surgery. The optimal device adapting for individual surgical manipulations should
be selected to make a VATS procedure safer and more feasible. The sample
extraction using a bag is a most important step when VATS is completed, because
the rupture of bag can result in cancer cell contamination. More useful devices
adapting either for mini-thoracotomy VATS or for port-access VATS, will be
developed with advancement of medical technology.
PMID- 25138946
TI - [Ultrasonically activated coagulating shears and the vessel sealing system in
thoracic surgery].
AB - While the recent emergence of energy-based surgical techniques has made surgical
procedures less invasive, the safety and proper usage have yet to be
investigated. Here we review the experimental and clinical use of ultrasonically
activated coagulating shears and a vessel sealing system in thoracic surgery.
Both energy devices have been reported to be safe for use with the pulmonary
artery and vein, with a burst pressure above 100 mmHg. Although their combined
use with a ligature at a central site appeared to be adequate, the long-term
durability has yet to be verified. The thoracic duct was reported to be sealed
with sufficient burst pressure using these energy devices, which are expected to
provide an alternative treatment for chylothorax. There have also been a few
reports of their usage with the lung parenchyma, but their clinical adaptation is
seemingly limited.
PMID- 25138947
TI - [Efficacy of soft coagulation in thoracic surgery].
AB - The soft coagulation is a novel mode of electrosurgical device which
automatically regulates its output voltage to stay below 190 Volts, causing pure
coagulation without carbonization. The soft coagulation is available with bipolar
and monopolar devices in thoracic surgery. Bipolar scissors can be applied for
dissection of pulmonary vessels safely and efficiently without the damage to
vessel wall. Monopolar soft coagulation can be applied to shrink bullous change
of lung, cease air leakage from lung parenchyme or bleeding from pulmonary
vessels.
PMID- 25138948
TI - [Overview of surgical stapling devices].
AB - Surgical stapler allows surgeons to do simultaneous cut and suture quickly in
excellent quality. Surgical stapler is currently used widely and has become
indispensable tool for thoracic surgery, especially for endoscopic surgery such
as thoracoscopic lung lobectomy, although there was some reluctance for use at
the dawn of the era of mechanical stapling device. Devices should be used for
right place in right manner. There are various kinds of stapling devices and
surgeons should follow manufactures' instruction appropriately to avoid possible
malfunctions of the devices. Surgeons must be aware of possible risks in use of
stapling devices and must learn pitfalls. Stapling devices do and will continue
to be evolved, and surgeons have to keep the know-how updated.
PMID- 25138949
TI - [Operation-assisted robot.da Vinci (lung)].
AB - The most favorable advantage of robotic surgery is the markedly free movement of
joint-equipped robotic forceps under 3-dimensional high-vision. Accurate
operation makes complex procedures straightforward and may overcome weak points
of previous thoracoscopic surgery. The efficiency and safety improves with
acquiring skills. However, the spread of robotic surgery in the general thoracic
surgery field has been delayed compared to those in other fields. The surgical
indications include primary lung cancer, thymic diseases, and mediastinal tumors,
but it is unclear whether technical advantages felt by operators are directly
connected to merits for patients. Moreover, problems concerning the cost and
education have not been solved. Although evidence is insufficient for robotic
thoracic surgery, it may be an extension of thoracoscopic surgery, and reports
showing its usefulness for primary lung cancer, myasthenia gravis, and thymoma
have been accumulating. Now, important thing is to carry out clinical trial for
advanced medical care and insurance acquisition. Although it is necessary to
solve important problems such as safety, education, training, the cost for the
future development, advancing robot technology has a possibility to markedly
change general thoracic surgery.
PMID- 25138950
TI - [Results of percutaneous cryoablation for malignant lung tumors compared with
radiotherapy].
AB - Radiotherapy has been regularly applied mainly for inoperable patients with non-
small cell lung cancer, and various clinical trials have been performed. On the
other hand, we have applied percutaneous cryoablation for lung tumors (PCLT)
since 2002. In this paper, we describe our experience of PCLT compared to the
results of radiation treatment. Three-year local progression-free rates with
stereotactic body radiotherapy were 79-92% in stage I A and 30-79% in stage I B.
Those with proton radiotherapy were 82-89% in stage I A and 49-62% in stage I B.
CTCAE grade >=3 complications occurred in 3-28% cases, such as radiation
pneumonitis. As for PCLT, 1-, 2- and 3-year local progression-free rates were
80.4%, 69.0% and 67.7%, respectively. Pneumothorax, pleural effusion, and
hemoptysis occurred after 61.7%, 70.5%, and 36.8% sessions, respectively. Of all
cases with pneumothorax, 17.6% required chest tube insertion and 1.7% required
pleurodesis. Delayed and recurrent pneumothorax occurred in 7.8% each. CTCAE
grade >=3 complications occurred in 1.5% cases. The biggest advantage of PCLT
compared with radiotherapy is the possibility to treat local recurrence at the
same site as treated before. In addition, no radiation pneumonitis occurs in
PCLT. Moreover, less space or budget is needed when PCLT is newly introduced in a
hospital. Although high reliable clinical data is not achieved yet, PCLT is one
of the promising methods in local treatment.
PMID- 25138951
TI - [Sentinel node identification of lung cancer].
AB - Sentinel node identification is important for small-sized non small cell lung
cancer patients who are candidates for segmentectomy in determining their
eligibilities. Intraoperative sentinel node identification using indocyanine
green or preoperative computed tomography lymphography by transbronchial
injection of iopamidol are suitable for daily medical practices, because these
methods take about only 10 minutes to identify sentinel nodes in addition to
routine surgical or bronchoscopic procedures.
PMID- 25138952
TI - [Infrared thoracoscopy].
AB - Infrared thoracoscopy with indocyanine green (ICG) is a new method of evaluating
lung perfusion. We succeeded in visualizing lung emphysematous lesions and
intersegmental borders using infrared thoracoscopy with ICG in animals, and
within clinical investigations. There are 2 methods in infrared thoracoscopy. One
is the 2-wavelength method, and the other is the 1-wavelength method. The 2-
wavelength method is based on ICG absorption, and the 1-wavelength method is
based on ICG fluorescence. The 2-wavelength method is superior for the clarity of
images. On the other hand, the 1-wavelength method is superior for the duration
of staining and the dose of ICG. Commonly, the inflation and deflation line has
been used to identify the intersegmental border, but lung reinflation narrows the
surgical view and can lead to prolongation of operation time, particularly in the
context of video-assisted thoracic surgery (VATS). Infrared thoracoscopy with ICG
is based on blood flow rather than on ventilation and can thus achieve anatomical
segmentectomy without lung reinflation. This article closely reviews the
principle and usefulness of infrared thoracoscopy, and difference between 2- and
1- wavelength method.
PMID- 25138953
TI - [Image-enhanced endoscopy and magnifying endoscopy for esophageal cancer].
AB - Image diagnoses for esophageal cancer are progressing. With regard to endoscopic
examination, chrome endoscopy using iodine have been performed so far to identify
the range of lesion and to detect multiple primary cancers. In addition to that,
endoscopic ultrasonography is used to diagnose the depth of tumor invasion and to
identify lymph node metastasis. Recently, image-enhanced endoscopy (IEE) [e.g.
Flexible spectral Imaging Color Enhancement (FICE), i-scan, Narrow Band Imaging
(NBI), Autofluorescence imaging (AFI)] has developed. IEE is useful to detect
superficial lesion, and is being utilized for diagnosing the tumor depth of
invasion by using magnifying endoscopy( ME) together. In this literature, recent
progress of endoscopic diagnosis, especially about IEE and ME, is reviewed. In
addition to that, a way of endoscopic examination using IEE and ME is introduced.
PMID- 25138954
TI - [Indocyanine green injection method for evaluating blood flow of gastric tube on
esophageal cancer surgery].
AB - The blood flow of esophageal substitute has been subjectively evaluated by
surgeons. HyperEye Medical System (HEMS) allows for the visualization of the
fluorescent image of indocyanine green (ICG) enhanced by near-infrared light
among the surrounding vivid color images. We applied HEMS for evaluating the
blood flow of right gastroepiploic artery and tissue blood flow of whole gastric
tube during operation. Quantification of arterial blood flow and venous return
has also been now developing for objective evaluation. We hope HEMS contributes
to development of surgical results on various fields by establishing
quantification of blood flow and clinical application.
PMID- 25138955
TI - [Thoracoscopic esophagectomy].
AB - In recent years, the number of facilities performing thoracoscopic surgery of the
esophagus has increased. Thoracoscopic surgery has many advantages, such as a
magnification effect, good lighting, and a wide field of view. Esophagectomy
requires fine manipulation within a deep and narrow space. Thus, thoracoscopic
surgery is suitable for the performance of esophagectomy. The body position
during this procedure may be either prone or left lateral decubitus. Because
there are advantages in both cases, the relative merits are controversial. The
operation time is longer than that of open thoracotomy, but the amount of
bleeding is small in most cases of thoracoscopic esophagectomy. There are also
some reports that thoracoscopic esophagectomy is comparable with open
esophagectomy in terms of radicality and quality of lymph node dissection, and
the intensive care unit and hospital stay durations are shortened. Robot-assisted
esophagectomy is a promising technology for the fine manipulations and high
quality 3-dimensional visualization required in the performance of esophageal
thoracoscopic surgery. Thoracoscopic esophagectomy will become more widespread
and undergo further development in the future with the spread of robotic surgery
and 3-dimensional endoscopic surgery.
PMID- 25138956
TI - Compressed-sensing-based fluorescence molecular tomographic image reconstruction
with grouped sources.
AB - BACKGROUND: Although the quality of reconstructed results can be improved with
the increment of the number of measurements, the scale of the matrices involved
in the reconstruction of fluorescence molecular tomography (FMT) will become
larger, which leads to the poor efficiency of the process of tomographic image
reconstruction. In this paper, we proposed a new method for image reconstruction
of FMT based on compressed sensing, in which a scheme of grouped sources is
incorporated. METHODS: The forward equations are implemented using the finite
element method (FEM). The reconstruction model is formulated under the framework
of compressed sensing theory. The regularization term and the total variation
penalty are incorporated in the objective function. During the reconstruction of
FMT, the sources are divided into two groups for iteration in turn. One group of
sources is employed in the first iteration of inverse problem, and the other
group is employed in the next iteration. RESULTS: Simulation results demonstrate
that the computation time and mean square error (MSE) of the reconstruction with
our algorithm are less than those with the traditional method. The proposed
algorithm can reconstruct the target with enhanced contrast and more accurate
shape. CONCLUSIONS: The proposed algorithm can significantly improve the speed
and accuracy of the reconstruction of FMT. Furthermore, our compressed-sensing
based method can reduce the number of measurements.
PMID- 25138958
TI - The beta-adrenoceptor agonist isoproterenol rescues acetaminophen-injured livers:
Is it really safe?
PMID- 25138959
TI - How Australian and New Zealand schools of optometry prepare students for
culturally competent practice.
AB - BACKGROUND: This study is an investigation of how Australian and New Zealand
schools of optometry prepare students for culturally competent practice. The aims
are: (1) to review how optometric courses and educators teach and prepare their
students to work with culturally diverse patients; and (2) to determine the
demographic characteristics of current optometric students and obtain their views
on cultural diversity. METHODS: All Australian and New Zealand schools of
optometry were invited to participate in the study. Data were collected with two
surveys: a curriculum survey about the content of the optometric courses in
relation to cultural competency issues and a survey for second year optometry
students containing questions in relation to cultural awareness, cultural
sensitivity and attitudes to cultural diversity. RESULTS: Four schools of
optometry participated in the curriculum survey (Deakin University, Flinders
University, University of Melbourne and University of New South Wales). Sixty
three students (22.3 per cent) from these four schools as well as the University
of Auckland participated in the student survey. Cultural competency training was
reported to be included in the curriculum of some schools, to varying degrees in
terms of structure, content, teaching method and hours of teaching. Among second
year optometry students across Australia and New Zealand, training in cultural
diversity issues was the strongest predictor of cultural awareness and
sensitivity after adjusting for school, age, gender, country of birth and
language other than English. CONCLUSION: This study provides some evidence that
previous cultural competency-related training is associated with better cultural
awareness and sensitivity among optometric students. The variable approaches to
cultural competency training reported by the schools of optometry participating
in the study suggest that there may be opportunity for further development in all
schools to consider best practice training in cultural competency.
PMID- 25138960
TI - Response to impact of obstructive sleep apnea on cardiovascular outcomes in
patients treated with percutaneous coronary intervention: rationale and design of
the sleep and stent study.
PMID- 25138961
TI - Low-resolution structures of OmpA?DDM protein-detergent complexes.
AB - We have used SAXS to determine the low-resolution structure of the outer-membrane
protein OmpA from E. coli solubilized by the surfactant dodecyl maltoside (DDM).
We have studied three variants of the transmembrane domain of OmpA-namely
monomers, self-associated dimers, and covalently linked dimers-as well as the
monomeric species of the full-length protein with the periplasmic domain. We can
successfully model the structures of the monomeric and covalently linked dimer as
one and two natively folded proteins in a DDM micelle, respectively, whereas the
noncovalently linked dimer presents a more complicated structure, possibly due to
higher-order species. We have determined the structure of the full-length protein
to be that of a globular periplasmic domain attached through a flexible linker to
the transmembrane domain. This approach provides valuable information about how
membrane proteins are embedded in amphiphilic environments.
PMID- 25138962
TI - Maximizing binding capacity for protein A chromatography.
AB - Advances in cell culture expression levels in the last two decades have resulted
in monoclonal antibody titers of >=10 g/L to be purified downstream. A high
capacity capture step is crucial to prevent purification from being the
bottleneck in the manufacturing process. Despite its high cost and other
disadvantages, Protein A chromatography still remains the optimal choice for
antibody capture due to the excellent selectivity provided by this step. A dual
flow loading strategy was used in conjunction with a new generation high capacity
Protein A resin to maximize binding capacity without significantly increasing
processing time. Optimum conditions were established using a simple empirical
Design of Experiment (DOE) based model and verified with a wide panel of
antibodies. Dynamic binding capacities of >65 g/L could be achieved under these
new conditions, significantly higher by more than one and half times the values
that have been typically achieved with Protein A in the past. Furthermore,
comparable process performance and product quality was demonstrated for the
Protein A step at the increased loading.
PMID- 25138964
TI - Graves' dermopathy and acropachy.
PMID- 25138963
TI - Adipogenic changes of hepatocytes in a high-fat diet-induced fatty liver mice
model and non-alcoholic fatty liver disease patients.
AB - Non-alcoholic fatty liver disease (NAFLD) is characterized by steatosis
associated with liver inflammation. As NAFLD progresses, triglycerides increase
within hepatocytes, causing typical vacuoles that resemble adipocytes. However,
whether these morphological changes in hepatocytes indicate potential functional
changes is unclear. C57BL/6J mice were fed a high-fat diet (HFD) containing 42%
fat. Markers for adipocytes in the liver were measured using real-time PCR,
Western blot, and double immunofluorescent labeling. Cytokines in cell culture
supernatants were quantified with ELISA. To determine the macrophage phenotype,
hepatic classical M1 markers and alternative M2 markers were analyzed. After a 24
week feeding period, adipocyte markers aP2 and PPARgamma increased at both the
mRNA and protein level in the liver of HFD-fed mice. FITC-labeled aP2 and
rhodamine-labeled albumin were both stained in the cytoplasm of steatotic
hepatocytes as observed under confocal laser scanning microscopy. Cell membrane
bound E-cadherin and albumin expression were reduced in steatotic hepatocytes
compared to controls. However, hepatic adiponectin and adiponectin receptor-2
expression decreased with upregulation of hepatic CD36, suggesting impaired
adiponectin activity in livers of HFD-fed mice. Moreover, steatotic primary
hepatocytes not only released pro-inflammatory cytokines such as TNFalpha, MCP-1,
IL-6, and IL-18, but also could activate macrophages when co-cultured in vitro.
In vivo, hepatic expression of M1 genes such as iNOS and TNFalpha was markedly
increased in HFD-fed mice. In contrast, hepatic expression of M2 genes such as
Arg1 and CD206 was significantly reduced. Specifically, the ratio of TNFalpha to
CD206 in HFD-fed mice was notably upregulated. Overexpression of adipocyte
specific genes in hepatocytes and their secretory function and epithelial
phenotype impairment in NAFLD cause functional changes in steatotic hepatocytes
aside from morphological changes. This suggests that adipogenic changes in
hepatocytes are involved in pathogenesis of NAFLD.
PMID- 25138965
TI - Water-mediated interactions between trimethylamine-N-oxide and urea.
AB - The amphiphilic osmolyte trimethylamine-N-oxide (TMAO) is commonly found in
natural organisms, where it counteracts biochemical stress associated with urea
in aqueous environments. Despite the important role of TMAO as osmoprotectant,
the mechanism behind TMAO's action has remained elusive. Here, we study the
interaction between urea, TMAO, and water in solution using broadband (100 MHz
1.6 THz) dielectric spectroscopy. We find that the previously reported tight
hydrogen bonds between 3 water molecules and the hydrophilic amine oxide group of
TMAO, remain intact at all investigated concentrations of urea, showing that no
significant hydrogen bonding occurs between the two co-solutes. Despite the
absence of direct TMAO-urea interactions, the solute reorientation times of urea
and TMAO show an anomalous nonlinear increase with concentration, for ternary
mixtures containing equal amounts of TMAO and urea. The nonlinear increase of the
reorientation correlates with changes in the viscosity, showing that the
combination of TMAO and urea cooperatively enhances the hydrogen-bond structure
of the ternary solutions. This nonlinear increase is indicative of water mediated
interaction between the two solutes and is not observed if urea is combined with
other amphiphilic solutes.
PMID- 25138967
TI - Influence of fluorescent dye on physical-mechanical properties of luting cements
for confocal microscopy analysis.
AB - AIMS: To evaluate the influence of a fluorescent dye (rhodamine B) on the
physical and mechanical properties of three different luting cements: a
conventional adhesive luting cement (RelyX ARC, 3M/ESPE), a self-adhesive luting
cement (RelyX U-200, 3M/ESPE), and a self-etching and self-adhesive luting cement
(SeT PP, SDI). MATERIALS AND METHODS: The cements were mixed with 0.03 wt%
rhodamine B, formed into bar-shaped specimens (n = 10), and light cured using an
LED curing unit (Radii, SDI) with a radiant exposure of 32 J/cm(2) . The Knoop
hardness (KHN), flexural strength (FS), and Young's modulus (YM) analyses were
evaluated after storage for 24 h. RESULTS: Outcomes were subjected to two-way
ANOVA and Tukey's test (P = 0.05) for multiple comparisons. No significant
differences in FS or YM were observed among the tested groups (P >= 0.05); the
addition of rhodamine B increased the hardness of the luting cements tested.
CONCLUSION: The addition of a fluorescent agent at 0.03 wt% concentration does
not negatively affect the physical-mechanical properties of the luting cement
polymerization behavior.
PMID- 25138966
TI - Oxygen uptake at different intensities and sub-techniques predicts sprint
performance in elite male cross-country skiers.
AB - PURPOSE: To investigate the relationship between sprint-prologue performance
(using the classical technique) and the oxygen uptake at the lactate threshold
(VO2obla), maximal oxygen uptake (VO2max), and mean oxygen uptake during double
poling (VO2dp). METHODS: Eight elite male cross-country skiers [age 24.8 +/- 4.8
years, (mean +/- SD)] completed two treadmill roller-skiing tests using the
diagonal-stride technique and a 60 s double-poling test on a ski-ergometer to
determine their VO2obla, VO2max, and VO2dp. Performance data were generated from
a 1.25 km sprint prologue. Power-function modelling was used to predict the
skiers' race speeds based on the oxygen-uptake variables and body mass. RESULTS:
There were correlations between the race speed and the absolute expression of the
VO2obla (r = 0.79, P = 0.021), VO2max (r = 0.86, P = 0.0069), and VO2dp (r =
0.94, P = 0.00062). The following power-function models were established for race
speed prediction: 1.09 . VO2obla(0.21), 1.05 . VO2max(0.21), and 1.19 .
VO2dp(0.20); these models explained 60% (P = 0.024), 73% (P = 0.0073), and 87% (P
= 0.00073), respectively, of the variance in the race speed. However, body mass
did not contribute to any of the models (P = 0.97, 0.88, and 0.21, respectively).
CONCLUSIONS: Oxygen uptake at different intensities and sub-techniques is an
indicator of elite male sprint-prologue performance. The absolute expression of
the investigated oxygen-uptake variables should be used when evaluating elite
male sprint-prologue performances; if skiers oxygen uptake differs by 1%, their
performances will likely differ by 0.2% in favour of the skier with higher oxygen
uptake.
PMID- 25138968
TI - Treatment of Complicated Spontaneous Twin Anemia-Polycythemia Sequence via
Fetoscopic Laser Ablation of the Vascular Communications.
AB - Monochorionic diamniotic twins share a single placenta and have intertwin
vascular communications that link the circulatory systems of the twins together.
Twin anemia-polycythemia sequence (TAPS) is an atypical form of twin-twin
transfusion syndrome (TTTS) caused by net transfer of blood from one fetus to the
other and is characterized by large intertwin hemoglobin differences in the
absence of oligohydramnios and polyhydramnios. This condition may develop
spontaneously (sTAPS) or as a result of residual vascular communications after
prior laser surgery. Because of the relatively low prevalence and lack of
clinical awareness, the natural history of sTAPS is unclear and the antenatal
treatment remains controversial. Case series of sTAPS have described expectant
management with timed delivery, intrauterine blood transfusion, and fetoscopic
laser treatment. Favorable outcomes have been described in cases of uncomplicated
sTAPS that underwent conservative measures. However, we believe that there may be
a subgroup of high-risk or complicated sTAPS patients that may benefit from
definitive treatment afforded by fetoscopic laser therapy. We describe 3
complicated cases of sTAPS successfully treated with selective laser
photocoagulation of communicating vessels. In 2 of the cases, placental pathology
identified thrombosed fetal vessels of the polycythemic twin.
PMID- 25138970
TI - West Nile virus lineage 2 isolated from Culex modestus mosquitoes in the Czech
Republic, 2013: expansion of the European WNV endemic area to the North?
AB - We report the detection and isolation of four almost identical strains of West
Nile virus (WNV) lineage 2from Culex modestus mosquitoes collected at three fish
ponds in South Moravia, Czech Republic, during August 2013. Phylogenetic analysis
demonstrated that the Czech WNV strains isolated are closely related to Austrian,
Italian and Serbian strains reported in 2008,2011 and 2012, respectively. Our
findings show the current northernmost range of lineage 2 WNV in Europe.
PMID- 25138969
TI - Coupling of sterically hindered trisubstituted olefins and benzocyclobutenones by
C-C activation: total synthesis and structural revision of cycloinumakiol.
AB - The first total syntheses of the proposed structure of cycloinumakiol (1) and its
C5 epimer (18) are achieved in a concise and efficient fashion. Starting from the
known 3-hydroxybenzocyclobutenone, 1 and 18 are obtained in nine and five steps
with overall yields of 15% and 33%, respectively. The key for the success of this
approach is the use of a catalytic C-C activation strategy for constructing the
tetracyclic core of 1 through carboacylation of a sterically hindered
trisubstituted olefin with benzocyclobutenone. In addition, the structure of the
natural cycloinumakiol was reassigned to 19-hydroxytotarol (7) through X-ray
diffraction analysis. This work demonstrates the potential of C-C activation for
streamlining complex natural product synthesis.
PMID- 25138971
TI - A multi-country outbreak of Salmonella Newport gastroenteritis in Europe
associated with watermelon from Brazil, confirmed by whole genome sequencing:
October 2011 to January 2012.
AB - In November 2011, the presence of Salmonella Newport in a ready-to-eat watermelon
slice was confirmed as part of a local food survey in England. In late December
2011, cases of S. Newport were reported in England, Wales, Northern Ireland,
Scotland, Ireland and Germany. During the outbreak, 63 confirmed cases of S.
Newport were reported across all six countries with isolates indistinguishable by
pulsed-field gel electrophoresis from the watermelon isolate.A subset of outbreak
isolates were whole-genome sequenced and were identical to, or one single
nucleotide polymorphism different from the watermelon isolate.In total, 46
confirmed cases were interviewed of which 27 reported watermelon consumption.
Further investigations confirmed the outbreak was linked to the consumption of
watermelon imported from Brazil.Although numerous Salmonella outbreaks associated
with melons have been reported in the United States and elsewhere, this is the
first of its kind in Europe.Expansion of the melon import market from Brazil
represents a potential threat for future outbreaks. Whole genome sequencing is
rapidly becoming more accessible and can provide a compelling level of evidence
of linkage between human cases and sources of infection,to support public health
interventions in global food markets.
PMID- 25138972
TI - Epidemiology and outcome of invasive pneumococcal disease among adults in
Belgium, 2009-2011.
AB - This epidemiological study examined morbidity and case fatality of invasive
pneumococcal disease (IPD) in adults in Belgium as well as distribution and
antibiotic susceptibility of Streptococcus pneumoniae serotypes.Adults
hospitalised with microbiologically proven IPD were prospectively enrolled. The
study started in 2009 with patients aged >=50 years, whereas in 2010 and 2011,
patients aged >=18 years were included. The clinical presentation, patient
profile, treatment, outcome, and mortality were recorded during
hospitalisation.Outcome was also assessed one month afterdischarge. Of the 1,875
patients with IPD identified, 1,332 were included in the analysis. Bacteraemic
pneumonia, affecting 1,049 of the patients, was the most frequent IPD type (79%),
and chronic obstructive pulmonary disease and cancer were the main
comorbidities.One-third of patients required admission to intensive care unit. A
total of 208 (16%) patients died during hospitalisation and an additional 21 (2%)
within one month after discharge. Case fatality rates of >=20%were observed in
patients with chronic heart failure, hepatic disease, and renal insufficiency.
Serotypes 7F, 1, 19A, and 3 were the most prevalent and together accounted for
47% (569/1,214) of all IPD cases and 42% (80/189) of mortality. Of the patient
isolates, 21% (255/1,204) were resistant to erythromycin and 22% (264/1,204) to
tetracycline. Penicillin non-susceptibility was mostly found in serotype 19A
isolates. These baseline data are essential when assessing the impact of
pneumococcal conjugate vaccination in adults in the future.
PMID- 25138973
TI - Information resources and latest news about Ebola virus disease available from
ECDC.
PMID- 25138974
TI - European Commission launches consultation on Science 2.0.
PMID- 25138977
TI - IL-17 and IL-22 serum levels in greenhouse workers exposed to pesticides.
AB - INTRODUCTION: Altered immune function may be an indicator of increased potential
for the development of immunologically based diseases such as cancer,
hypersensitivity and autoimmunity. MATERIALS AND METHODS: To investigate whether
Th17 and Th22 cells are targeted by pesticide exposure, we analyzed IL-17 and IL
22 serum levels in a population of 64 greenhouse workers. RESULTS AND CONCLUSION:
A significant increase in IL-22 concentration was observed in serum of the
exposed subjects compared to controls. These findings support the hypothesis that
exposure to pesticides may reduce host defenses against infections and cancer.
PMID- 25138978
TI - Operating characteristics of PROMIS four-item depression and anxiety scales in
primary care patients with chronic pain.
AB - OBJECTIVE: Depression and anxiety are prevalent in patients with chronic pain and
adversely affect pain, quality of life, and treatment response. The purpose of
this psychometric study was to determine the reliability and validity of the four
item Patient Reported Outcomes Measurement Information System (PROMIS) depression
and anxiety scales in patients with chronic pain. DESIGN: Secondary analysis of
data from the Stepped Care to Optimize Pain care Effectiveness study, a
randomized clinical trial of optimized analgesic therapy. SETTING: Five primary
care clinics at the Roudebush VA Medical Center (RVAMC) in Indianapolis, Indiana.
SUBJECTS: Two hundred forty-four primary care patients with chronic
musculoskeletal pain. METHODS: All patients completed the four-item depression
and anxiety scales from the PROMIS 29-item profile, as well as several other
validated psychological measures. The minimally important difference (MID) using
the standard error of measurement (SEM) was calculated for each scale, and
convergent validity was assessed by interscale correlations at baseline and 3
months. Operating characteristics of the PROMIS measures for detecting patients
who had probable major depression or were anxiety-disorder screen-positive were
calculated. RESULTS: The PROMIS scales had good internal reliability, and the MID
(as represented by two SEMs) was 2 points for the depression scale and 2.5 points
for the anxiety scale. Convergent validity was supported by strong interscale
correlations. The optimal screening cutpoint on the 4- to 20-point PROMIS scales
appeared to be 8 for both the depression and anxiety scales. CONCLUSIONS: The
PROMIS four-item depression and anxiety scales are reasonable options as ultra
brief measures for screening in patients with chronic pain.
PMID- 25138979
TI - Early-onset Alzheimer's disease in two Iranian families: a genetic study.
AB - BACKGROUND: Early-onset Alzheimer's disease (EOAD) represents less than 5% of all
AD cases. Autosomal dominant EOAD has been defined as the occurrence of at least
three cases in three generations. Mutations in the amyloid precursor protein
(APP), presenilin-1 and presenilin-2 genes have been recognized to be the cause
of EOAD. OBJECTIVE: We investigated the genotype of EOAD in two generations of
two families with EOAD living in an Iranian village. METHODS: The polymerase
chain reaction method was used to study the presenilin-1 and APP genes in 25
subjects of these generations. RESULTS: A guanine-to-adenine transition in exon
17 of the APP gene resulting in a valine-to-isoleucine substitution at codon 717
was detected in 14 subjects including 6 patients with EOAD. CONCLUSION: This
mutation demonstrates the importance of gamma-secretase, the necessity of early
detection of patients with memory decline in the susceptible population and
raising public awareness of consanguinity marriages.
PMID- 25138980
TI - Surgical versus conservative treatment for high-risk stress fractures of the
lower leg (anterior tibial cortex, navicular and fifth metatarsal base): a
systematic review.
AB - AIM: To compare surgical and conservative treatment for high-risk stress
fractures of the anterior tibial cortex, navicular and proximal fifth metatarsal.
METHODS: Systematic searches of CENTRAL, MEDLINE, EMBASE, CINAHL, SPORTDiscus and
PEDro were performed to identify relevant prospective and retrospective studies.
Two reviewers independently extracted data and assessed methodological quality.
Main outcomes were return to sport and complication rate. RESULTS: 18 studies
were included (2 anterior tibia (N=31), 8 navicular (N=200) and 8 fifth
metatarsal (N=246)). For anterior tibial fracture, no studies on initial surgery
were eligible. Conservative treatment resulted in high complication rates and few
cases returned to sport. For navicular fracture, a weighted mean return to sport
of 22 for conservative and 16 weeks for surgical treatment was found. Six weeks
of non-weightbearing cast was mostly used as conservative treatment. Surgical
procedures varied widely. For the fifth metatarsal fracture, weighted mean return
to sport was 19 for conservative and 14 weeks for surgical treatment. Surgery
consisted of intramedullary screw fixation or tension band wiring. For
conservative methods, insufficient details were reported. Overall, there was a
high risk of bias; sample sizes were small and GRADE level of evidence was low.
CONCLUSIONS: Strong conclusions for surgical or conservative therapy for these
high-risk stress fractures cannot be drawn; quality of evidence is low and
subjected to a high risk of bias. However, there are unsatisfying outcomes of
conservative therapy in the anterior tibia. The role of initial surgery is
unknown. For the navicular, surgery provided an earlier return to sport; and when
treated conservatively, weightbearing should be avoided. For the fifth
metatarsal, surgery provided the best results. Treatment decision-making would
greatly benefit from further prospective research. STUDY REGISTRATION NUMBER:
PROSPERO database of systematic reviews: CRD42013004201.
PMID- 25138982
TI - Cancer Knowledge and Opportunities for Education Among HIV-Infected Patients in
an Urban Academic Medical Center.
AB - HIV-infected patients frequently present with advanced stage cancer. It is
possible that late stage presentation may be related to lack of cancer knowledge
and/or barriers to care. Questionnaires were administered to 285 adult HIV
infected patients to evaluate knowledge of cancer risk factors and symptoms and
barriers to care between 2011 and 2012. Differences in mean and percent scores by
group were assessed using a t test for independent samples and chi-square
analysis, respectively. Respondents were predominantly male (64%), African
American (86%), and low income (60% < $10,000/year). Thirty-four (12%) had been
diagnosed with cancer, and 169 (59%) had a family history of cancer. The mean
knowledge score was 17.5 out of 24 questions (73%). Mean scores were not
significantly different by sex, age, race, or income. Respondents with a college
education scored significantly higher than those with less than a high school
education (p < 0.01). In unadjusted analysis, a higher proportion of patients
with a personal/family history of cancer (74%) scored in the highest quartile
(>70% correct) compared to those without any personal history of cancer (62%) (p
= 0.03). There was a higher level of cancer knowledge in this population compared
to studies that have evaluated the HIV-uninfected population. Nevertheless, there
were knowledge deficits, suggesting the need for further education about cancer
to improve earlier detection rates and, ultimately, outcomes.
PMID- 25138984
TI - Molecular interactions driving the layer-by-layer assembly of multilayers.
PMID- 25138983
TI - Older women's experience with a benign breast biopsy-a mixed methods study.
AB - BACKGROUND: Little is known about older women's experience with a benign breast
biopsy. OBJECTIVES: To examine the psychological impact and experience of women
>= 65 years of age with a benign breast biopsy. DESIGN: Prospective cohort study
using quantitative and qualitative methods. SETTING: Three Boston-based breast
imaging centers. PARTICIPANTS: Ninety-four English-speaking women >= 65 years
without dementia referred for breast biopsy as a result of an abnormal mammogram,
not aware of their biopsy results at baseline, and with a subsequent negative
biopsy. MEASUREMENTS: We interviewed women at the time of breast biopsy (before
women knew their results) and 6 months post-biopsy. At both interviews,
participants completed the validated negative psychological consequences of
screening mammography questionnaire (PCQ, scores range from 0 to 36 [high
distress], PCQ >= 1 suggests a psychological consequence, PCQs <1 are reported at
time of screening) and women responded to open-ended questions about their
experience. At follow-up, participants described the quality of information
received after their benign breast biopsy. We used a linear mixed effects model
to examine if PCQs declined over time. We also reviewed participants' open-ended
comments for themes. RESULTS: Overall, 88% (83/94) of participants were non
Hispanic white and 33% (31/94) had a high-school degree or less. At biopsy, 76%
(71/94) reported negative psychological consequences from their biopsy compared
to 39% (37/94) at follow-up (p < 0.01). In open-ended comments, participants
noted the anxiety (29%, 27/94) and discomfort (28%, 26/94) experienced at biopsy
(especially from positioning on the biopsy table). Participants requested more
information to prepare for a biopsy and to interpret their negative results.
Forty-four percent (39/89) reported at least a little anxiety about future
mammograms. CONCLUSIONS: The high psychological burden of a benign breast biopsy
among older women significantly diminishes with time but does not completely
resolve. To reduce this burden, older women need more information about
undergoing a breast biopsy.
PMID- 25138986
TI - The impact of intolerance of uncertainty, worry and irritability on quality of
life in persons with epilepsy: irritability as mediator.
AB - Epilepsy is a neurological disorder afflicting many people in the world. The
impact of epilepsy on the quality of life of those afflicted with epilepsy is
greater than the limitations imposed by the seizures alone. Among the several
psychological disorders found to be comorbid with epilepsy are anxiety and
depression, both of which impair quality of life in epilepsy. Some studies have
reported that the anxiety seen in epilepsy is characterized by worry while the
depression seen is characterized by irritability. A concept common to both
anxiety and depression is intolerance of uncertainty. Therefore, the study
explores the relationship between intolerance of uncertainty, worry and
irritability and their association to quality of life in epilepsy. A descriptive
correlational research method was used and the research sample comprised 60
consecutive referrals seeking outpatient neurological services for epilepsy at
Alavi Hospital in Ardebil. Data were collected by administering the Penn State
Worry Questionnaire, Intolerance of Uncertainty Scale, Irritability Questionnaire
and Quality of Life in Epilepsy Inventory. Data were analyzed using Pearson's
correlation coefficients and multivariate regression analysis. Mediation and
moderation analyses were conducted. Findings indicated that intolerance of
uncertainty, worry and irritability have unique significant effects on quality of
life. The implications are that interventions aimed at improving the quality of
life of patients with epilepsy should address their feelings of uncertainty,
worry and irritability. Furthermore, irritability seems to mediate the impact of
both intolerance of uncertainty and worry on quality of life of individuals with
epilepsy. No significant moderation effects were noted. Results underscore the
important role of irritability in the quality of life of persons with epilepsy.
The findings are discussed with reference to the possibility of particular
predisposing temperaments and add credence to the suggestion of an epileptic
personality.
PMID- 25138985
TI - Serum levels of M-CSF, RANKL and OPG in rats fed with Kashin-Beck disease
affected diet.
AB - OBJECTIVE: There were no studies on the macrophage colony-stimulating factor (M
CSF), receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) in
the pathogenesis of Kashin-Beck disease (KBD). The objective of the present study
was to investigate the serum M-CSF, RANKL and OPG in rats fed with KBD-affected
diet. METHODS: Ninety Wistar rats were divided into five groups. The rats
received standard commercial feed with or without T-2 toxin additive, low protein
feed with or without or T-2 toxin additive and the KBD-affected feed. The serum
bioactivity of M-CSF, RANKL and OPG was tested by enzyme-linked immunosorbent
assay. RESULTS: The serum levels of M-CSF in E group rats were higher than those
in the other groups in the five groups (P < 0.01). The serum levels of RANKL and
OPG in E group rats were highest in the five groups and have significant
difference compared to the other groups (P < 0.05). CONCLUSIONS: The molecule of
M-CSF, RANKL and OPG may be involved in the regulation of epiphyseal plate injury
and repair in KBD, and its participation in the pathogenesis of KBD should be
studied in the future.
PMID- 25138987
TI - Calcification of the internal pudendal artery and development of erectile
dysfunction in adenine-induced chronic kidney disease: a sentinel of systemic
vascular changes.
AB - INTRODUCTION: Chronic kidney disease (CKD), erectile dysfunction (ED), and
cardiovascular disease share common vascular etiologies and risk factors. AIM:
Using a rat model, this is the first study to characterize the consequences of
CKD in the onset and development of ED associated with differential regional
vascular calcification and circulatory changes. METHODS: Stable CKD was generated
at 3 weeks in male Sprague-Dawley rats given dietary adenine and progressed until
7 weeks. Mineral content and morphometry were assessed in the internal pudendal
arteries (IPAs), thoracic aorta, and carotid artery. Endothelial function was
determined via changes in serum von Willebrand factor (VWF) and endothelium
dependent relaxation of the thoracic aorta. RESULTS: In severe CKD rats, calcium
and phosphate content in all arteries increased, and pulse wave velocity was
elevated. Distal IPA segments, in particular, were the first to calcify, but
penile tissue per se did not. CKD rats had endothelial dysfunction, as indicated
by a decrease in acetylcholine-mediated relaxation (~40%) and an increase in
serum VWF (~40%), as well as increased lumen diameter (20%) of the distal IPA.
Erectile function, assessed using a centrally acting dopaminergic agent, was
significantly impaired by 7 weeks (~40%). CONCLUSIONS: In CKD, the distal IPA
appears to be more susceptible to vascular dysfunction and calcification.
Additionally, the onset of ED may be an important sentinel of impending systemic
vascular disease. To confirm this concept, future experimental and clinical
studies will need to examine a range of vessel types and the use of supplementary
methods to assess erectile function.
PMID- 25138988
TI - Treatment effects of a fixed intermaxillary device to correct class II
malocclusions in growing patients.
AB - BACKGROUND: The objective of this study was to evaluate the treatment effects of
ForsusTM Fatigue Resistant Device (FRD; 3M Unitek, Monrovia, CA, USA) in growing
patients with Class II non-extraction malocclusions. METHODS: A retrospective
sample of 24 class II patients treated consecutively with the FRD followed by
comprehensive orthodontic treatment was compared to a sample of untreated control
subjects from the Bolton Brush Study who was matched in age, sex, and
craniofacial morphology. Lateral cephalometric radiographs were taken before
treatment (T1) and after removal of fixed appliances (T2). Growth changes were
subtracted from the treatment changes to obtain the treatment effects of the
appliance. Data were analyzed using ANOVA and a match paired t test. RESULTS:
Significant differences were found between the treated and control groups for 12
of the 29 measured variables (Co-Gn minus Co-Apt, Wits, Is-OLp, Ii-OLp, overjet,
Mi-OLp, molar relationship, overbite, Mic-ML, SNA, ANB, and Ii-ML). With 27.8
months of treatment, all patients were corrected to a class I dental arch
relationship. Overjet and molar relationships were improved by an average of 4.7
and 3.1 mm, respectively. This was contributed by a 1.2 mm of restraint in
forward maxillary growth, 0.7 mm of forward movement of the mandible, 1.5 mm of
backward movement of the maxillary incisors, 1.3 mm forward movement of the
mandibular incisors, 0.5 mm backward movement of the maxillary molars, and 1.3 mm
of forward movement of the mandibular molars. The overbite was decreased by 2 mm
with no significant change in the occlusal, palatal, or mandibular plane.
Individual variations in response to the FRD treatment were large for most of the
parameters tested. Significant differences in treatment changes between male and
female subjects were found only in a few parameters measured. CONCLUSIONS: These
results demonstrate that significant overjet and overbite corrections can be
obtained with the Forsus FRD in conjunction with comprehensive orthodontic
treatment.
PMID- 25138989
TI - Hyperplasia of rib and vertebra, associated with infiltrating lipoma: a rare case
of focal overgrowth.
AB - PURPOSE: Syndromes with focal overgrowth are rare and diagnosis is difficult
because manifestations are highly variable and symptoms overlap between
syndromes. Diagnosis depends on clinical history, physical examination, and
radiologic and histologic findings. This report describes a case of focal
overgrowth of the left seventh rib and half of the adjacent thoracic vertebra,
with overlying infiltrating lipoma. METHODS: A 13-year-old boy presented with an
asymptomatic chest wall mass caused by enlargement of the seventh rib and an
overlying soft-tissue mass accompanied by enlargement of half of the seventh
thoracic vertebra. MRI showed infiltration of lipomatous tissue in the muscles,
but no interfascicular accumulation of adipose tissue in the thoracic spinal
nerve. RESULTS: A similar case was presented in 1985 but without MR imaging.
CONCLUSION: We report on a second case of focal overgrowth of a rib and half of
the adjacent vertebra, and overlying lipoma. In addition to the first case, we
present MR images demonstrating infiltration of the adipose tissue.
PMID- 25138990
TI - PlasmaKineticTM versus cold knife internal urethrotomy in terms of recurrence
rates: a prospective randomized study.
AB - OBJECTIVE: To evaluate the efficacy and outcomes of PlasmaKineticTM urethrotomy
against cold knife direct vision internal urethrotomy in terms of recurrence
rates. PATIENTS AND METHODS: A total of 136 male patients with urethral
strictures were enrolled into the study. The patients were allocated to cold
knife or PlasmaKinetic urethrotomy groups sequentially by using computer
generated numbers. Group A (PlasmaKinetic) and group B (cold knife) included 70
and 66 patients, respectively. All patients were reevaluated at the 3rd, 9th and
18th month postoperatively with uroflowmetry. RESULTS: Group A patients had a
postoperative 3rd-month maximum flow rate value of 16.09 ml/s, whereas this same
parameter was 15.15 ml/s in group B (p < 0.05). The urethral stricture recurrence
rate up to the 9-month period was statistically significant for group A (14%)
compared with group B (30%). When we compared the recurrence rates of these
groups from postoperative day 1 up to the 18th month, the results were 37% for
group A and 33% for group B (p > 0.05). CONCLUSION: PlasmaKinetic urethrotomy
provides a better recurrence-free rate during the early period compared with
conventional cold knife therapy. Nevertheless, the outcome of the stricture did
not change and fibrotic tissue reformed between the 9th and the 18th month.
PMID- 25138991
TI - Blood-brain barrier drug delivery of IgG fusion proteins with a transferrin
receptor monoclonal antibody.
AB - INTRODUCTION: Biologic drugs are large molecules that do not cross the blood-
brain barrier (BBB). Brain penetration is possible following the re-engineering
of the biologic drug as an IgG fusion protein. The IgG domain is a MAb against an
endogenous BBB receptor such as the transferrin receptor (TfR). The TfRMAb acts
as a molecular Trojan horse to ferry the fused biologic drug into the brain via
receptor-mediated transport on the endogenous BBB TfR. AREAS COVERED: This review
discusses TfR isoforms, models of BBB transport of transferrin and TfRMAbs, and
the genetic engineering of TfRMAb fusion proteins, including BBB penetrating IgG
neurotrophins, IgG-decoy receptors, IgG-lysosomal enzyme therapeutics and IgG
avidin fusion proteins, as well as BBB transport of bispecific antibodies formed
by fusion of a therapeutic antibody to a TfRMAb targeting antibody. Also
discussed are quantitative aspects of the plasma pharmacokinetics and brain
uptake of TfRMAb fusion proteins, as compared to the brain uptake of small
molecules, and therapeutic applications of TfRMAb fusion proteins in mouse models
of neural disease, including Parkinson's disease, stroke, Alzheimer's disease and
lysosomal storage disorders. The review covers the engineering of TfRMAb-avidin
fusion proteins for BBB targeted delivery of biotinylated peptide
radiopharmaceuticals, low-affinity TfRMAb Trojan horses and the safety
pharmacology of chronic administration of TfRMAb fusion proteins. EXPERT OPINION:
The BBB delivery of biologic drugs is possible following re-engineering as a
fusion protein with a molecular Trojan horse such as a TfRMAb. The efficacy of
this technology will be determined by the outcome of future clinical trials.
PMID- 25138992
TI - Supportive post-implant therapy: patient compliance rates and impacting factors:
3-year follow-up.
AB - AIM: To evaluate patient compliance rates and influential factors regarding a
systematic SIT program. MATERIALS AND METHODS: Between 2005 and 2008, we
identified all patients who were provided with implant-supported restorations in
the study centre. They had been recommended to attend a SIT program with a 3
month recall. In 2012, a clinical retrospective cohort study on compliance rates
over the first 3 years was performed different data were assessed in a regression
analysis to identify potential influential factors. RESULTS: The inclusion
criteria were met by 236 patients with 540 implants. Non-compliance rates
increased over the 3 years (5.37%/7.78%/13.33%). Total non-compliance was
observed in four patients (1.69%). No correlation to patient compliance was
detected for "Age," "Gender," "Cardiovascular disease," "Pus/suppuration," or
"Surgical case complexity." No decreasing effect of higher compliance rates on
the patients' bleeding on probing (BOP+) values was found, but a statistical
significance between lower compliance rates and increased pocket probing depth
(PPD) was detected. The correlation between the presence of plaque and compliance
did not reach statistical significance. CONCLUSIONS: When patients with implant
supported restorations are strongly recommended to comply with a SIT program with
a 3-month recall, considerably high rates of compliance can be achieved.
PMID- 25138993
TI - Differential association between metabolic syndrome and coronary artery disease
evaluated with cardiac computed tomography according to the presence of diabetes
in a symptomatic Korean population.
AB - BACKGROUND: Metabolic syndrome (MetS) is associated with increased risks of
diabetes and coronary artery disease (CAD). Despite the controversial inclusion
of established diabetes in MetS, the association between MetS and CAD according
to diabetes status has not been elucidated in the Asian population. METHODS: We
evaluated the association between MetS and CAD using the parameters including any
plaque, obstructive plaque, and coronary artery calcium score (CACS) >100
according to diabetes status in 2,869 symptomatic Korean subjects who underwent
cardiac computed tomographic angiography. RESULTS: The prevalence of MetS was
significantly higher in the diabetic subjects than in the non-diabetic subjects
(69% vs. 34%, P <0.001). The incidence of any plaque (64% vs. 43%, P <0.001),
obstructive plaque (26% vs. 13%, P = 0.006), and CACS >100 (23% vs. 12%, P =
0.012) was significantly higher in diabetic subjects than in non-diabetic
subjects. Among the MetS components, decreased high-density lipoprotein level was
significantly associated with any plaque (odds ratio [OR] 1.35), obstructive
plaque (OR 1.55), and CACS >100 (OR 1.57) in the non-diabetic subjects (P <0.01,
respectively). However, none of the MetS components were associated with all the
parameters in the diabetic subjects. Multivariate regression analysis revealed
that MetS and the number of MetS components (MetSN) were independently associated
with any plaque (MetS: OR 1.55, P <0.001; MetSN: OR 1.22, P <0.001), obstructive
plaque (MetS: OR 1.52, P = 0.003; MetSN: OR 1.25, P <0.001), and CACS >100 (MetS:
OR 1.46, P = 0.015; MetSN: OR 1.21, P = 0.004) only in the non-diabetic subjects,
respectively. CONCLUSIONS: MetS was independently associated with the presence
and severity of CAD only in the non-diabetic subjects among the symptomatic
Korean population.
PMID- 25138995
TI - Mental disorder and suicide: a faulty connection.
PMID- 25138994
TI - Developing zebrafish models relevant to PTSD and other trauma- and stressor
related disorders.
AB - While post-traumatic stress disorder (PTSD) and other trauma- and stress-related
disorders (TSRDs) represent a serious societal and public health concern, their
pathogenesis is largely unknown. Given the clinical complexity of TSRD
development and susceptibility, greater investigation into candidate biomarkers
and specific genetic pathways implicated in both risk and resilience to trauma
becomes critical. In line with this, numerous animal models have been extensively
used to better understand the pathogenic mechanisms of PTSD and related TSRD.
Here, we discuss the rapidly increasing potential of zebrafish as models of these
disorders, and how their use may aid researchers in uncovering novel treatments
and therapies in this field.
PMID- 25138996
TI - 'I move therefore I am': the anoetic ideomotor theory of autism.
PMID- 25138997
TI - The importance of mental disorders in suicide.
PMID- 25138999
TI - Training experience in gestures affects the display of social gaze in baboons'
communication with a human.
AB - Gaze behaviour, notably the alternation of gaze between distal objects and social
partners that accompanies primates' gestural communication is considered a
standard indicator of intentionality. However, the developmental precursors of
gaze behaviour in primates' communication are not well understood. Here, we
capitalized on the training in gestures dispensed to olive baboons (Papio anubis)
as a way of manipulating individual communicative experience with humans. We
aimed to delineate the effects of such a training experience on gaze behaviour
displayed by the monkeys in relation with gestural requests. Using a food
requesting paradigm, we compared subjects trained in requesting gestures (i.e.
trained subjects) to naive subjects (i.e. control subjects) for their occurrences
of (1) gaze behaviour, (2) requesting gestures and (3) temporal combination of
gaze alternation with gestures. We found that training did not affect the
frequencies of looking at the human's face, looking at food or alternating gaze.
Hence, social gaze behaviour occurs independently from the amount of
communicative experience with humans. However, trained baboons-gesturing more
than control subjects-exhibited most gaze alternation combined with gestures,
whereas control baboons did not. By reinforcing the display of gaze alternation
along with gestures, we suggest that training may have served to enhance the
communicative function of hand gestures. Finally, this study brings the first
quantitative report of monkeys producing requesting gestures without explicit
training by humans (controls). These results may open a window on the
developmental mechanisms (i.e. incidental learning vs. training) underpinning
gestural intentional communication in primates.
PMID- 25139000
TI - Predators in training: operant conditioning of novel behavior in wild Burmese
pythons (Python molurus bivitattus).
AB - Large pythons and boas comprise a group of animals whose anatomy and physiology
are very different from traditional mammalian, avian and other reptilian models
typically used in operant conditioning. In the current study, investigators used
a modified shaping procedure involving successive approximations to train wild
Burmese pythons (Python molurus bivitattus) to approach and depress an
illuminated push button in order to gain access to a food reward. Results show
that these large, wild snakes can be trained to accept extremely small food
items, associate a stimulus with such rewards via operant conditioning and
perform a contingent operant response to gain access to a food reward. The
shaping procedure produced robust responses and provides a mechanism for
investigating complex behavioral phenomena in massive snakes that are rarely
studied in learning research.
PMID- 25138998
TI - The opioid system and brain development: effects of methadone on the
oligodendrocyte lineage and the early stages of myelination.
AB - Oligodendrocytes express opioid receptors throughout development, but the role of
the opioid system in myelination remains poorly understood. This is a significant
problem as opioid use and abuse continue to increase in two particular
populations: pregnant addicts (in whom drug effects could target early
myelination in the fetus and newborn) and adolescents and young adults (in whom
late myelination of 'higher-order' regions takes place). Maintenance treatments
for opioid addicts include the long-lasting opioids methadone and buprenorphine.
Similar to our previous findings on the effects of buprenorphine, we have now
found that early myelination in the developing rat brain is also altered by
perinatal exposure to therapeutic doses of methadone. Pups exposed to this drug
exhibited elevated brain levels of the 4 major splicing variants of myelin basic
protein, myelin proteolipid protein, and myelin-oligodendrocyte glycoprotein.
Consistent with the enrichment and function of these proteins in mature myelin,
analysis of the corpus callosum in these young animals also indicated an elevated
number of axons with already highly compacted myelin sheaths. Moreover, studies
in cultured cells showed that methadone exerts direct effects at specific stages
of the oligodendrocyte lineage, stimulating the proliferation of progenitor cells
while on the other hand accelerating the maturation of the more differentiated
but still immature preoligodendrocytes. While the long-term effects of these
observations remain unknown, accelerated or increased oligodendrocyte maturation
and myelination could both disrupt the complex sequence of synchronized events
leading to normal connectivity in the developing brain. Together with our
previous observations on the effects of buprenorphine, the present findings
further underscore a crucial function of the endogenous opioid system in the
control of oligodendrocyte development and the timing of myelination.
Interference with these regulatory systems by opioid use or maintenance
treatments could disrupt the normal process of brain maturation at critical
stages of myelin formation.
PMID- 25139001
TI - Changes in perceptual speed and white matter microstructure in the corticospinal
tract are associated in very old age.
AB - The integrity of the brain's white matter is important for neural processing and
displays age-related differences, but the contribution of changes in white matter
to cognitive aging is unclear. We used latent change modeling to investigate this
issue in a sample of very old adults (aged 81-103 years) assessed twice with a
retest interval of 2.3 years. Using diffusion-tensor imaging, we probed white
matter microstructure by quantifying mean fractional anisotropy and mean
diffusivity of six major white matter tracts. Measures of perceptual speed,
episodic memory, letter fluency, category fluency, and semantic memory were
collected. Across time, alterations of white matter microstructure in the
corticospinal tract were associated with decreases of perceptual speed. This
association remained significant after statistically controlling for changes in
white matter microstructure in the entire brain, in the other demarcated tracts,
and in the other cognitive abilities. Changes in brain volume also did not
account for the association. We conclude that white matter microstructure is a
potent correlate of changes in sensorimotor aspects of behavior in very old age,
but that it is unclear whether its impact extends to higher-order cognition.
PMID- 25139003
TI - Magnetic resonance imaging evaluation of lipodystrophy in HIV-positive patients
receiving highly active antiretroviral therapy.
AB - We evaluated retrospectively an automated method for the separate detection of
subcutaneous and visceral fat in the abdominal region by magnetic resonance
studies in HIV-positive patients on highly active antiretroviral therapy. The
patients were divided into four different groups: lipoatrophy, lipohypertrophy,
mixed and the control group. The use of software for the automated detection of
abdominal compartment visceral adipose tissue (VAT), total adipose tissue (TAT)
and subcutaneous adipose tissue (SAT) was compared to manual evaluation methods
(fuzzy C-mean). The results of ROC analysis showed that the parameters,
particularly the VAT, are better than the VAT/TAT and at identifying patients
with the symptoms of abdominal fat accumulation. A sensitivity of 80.3% and a
specificity of 79.5% resulted from a threshold VAT value of >87 cm(2). Moreover,
the manual evaluation method was shown to provide greater values for VAT and the
VAT/TAT ratio than those given by the automated method. In the present study, a
rapid MRI protocol for the detection and assessment of the course of
lipodystrophy was presented and tested on a group of patients with signs of HALS,
as well as on an antiretroviral naive control group.
PMID- 25139004
TI - Access to post-exposure prophylaxis following sexual exposure for men who have
sex with men in an Irish healthcare setting.
AB - Men who have sex with men experience disproportionate rates of HIV acquisition.
Post-exposure prophylaxis following unprotected sexual exposure reduces HIV
transmission. Our aim was to assess access to post-exposure prophylaxis for men
who have sex with men in Irish emergency departments. We contacted all national
24-hour adult emergency departments describing two scenarios; a seronegative man
who has sex with men receiving unprotected insertive anal intercourse from a
seropositive partner and secondly a woman sustaining a needle-stick injury from
an unknown source. We recorded and compared responses regarding post-exposure
prophylaxis advice in each situation. High proportions of emergency departments
offered post-exposure prophylaxis for both situations despite minimal evidence to
support use in needle-stick injury. Men who have sex with men were less likely to
be asked to attend emergency departments for post-exposure prophylaxis
administration than a person experiencing needle-stick injury. Men who have sex
with men were less likely to be offered baseline serological testing for blood
borne infections. Men who have sex with men were as likely as needle-stick injury
to receive advice from healthcare workers in emergency departments and
consultation durations were similar. This study identifies a need to educate
healthcare workers in emergency departments on appropriate use of post-exposure
prophylaxis following sexual exposure for men who have sex with men. Health care
workers must appreciate the importance of post-exposure prophylaxis presentations
as opportunities for intervention and HIV screening.
PMID- 25139002
TI - Reduced mediodorsal thalamic volume and prefrontal cortical spindle activity in
schizophrenia.
AB - BACKGROUND: We recently found marked deficits in sleep spindles, non-rapid eye
movement (NREM) sleep oscillations that are generated within the thalamus and
then amplified and sustained in the cortex, in patients with schizophrenia
compared to both healthy and psychiatric controls. Here, we investigated the
thalamic and cortical contributions to these sleep spindle deficits. METHODS:
Anatomical volume of interest analysis (i.e., thalamic volumes) and
electroencephalogram (EEG) source modeling (i.e., spindle-related cortical
currents) were performed in patients with schizophrenia and healthy comparison
subjects. FINDINGS: Schizophrenia patients had reduced mediodorsal (MD) thalamic
volumes, especially on the left side, compared to healthy controls, whereas whole
thalami and lateral geniculate nuclei did not differ between groups. Furthermore,
left MD volumes were strongly correlated with the number of scalp-recorded
spindles in an anterior frontal region, and cortical currents underlying these
anterior frontal spindles were localized in the prefrontal cortex, in Brodmann
area (BA) 10. Finally, prefrontal currents at the peak of spindle activity were
significantly reduced in schizophrenia patients and correlated with their
performance in an abstraction/working memory task. CONCLUSION: Altogether, these
findings point to deficits in a specific thalamo-cortical circuitry in
schizophrenia, which is associated with some cognitive deficits commonly reported
in those patients.
PMID- 25139005
TI - Model-assisted analysis of sugar metabolism throughout tomato fruit development
reveals enzyme and carrier properties in relation to vacuole expansion.
AB - A kinetic model combining enzyme activity measurements and subcellular
compartmentation was parameterized to fit the sucrose, hexose, and glucose-6-P
contents of pericarp throughout tomato (Solanum lycopersicum) fruit development.
The model was further validated using independent data obtained from domesticated
and wild tomato species and on transgenic lines. A hierarchical clustering
analysis of the calculated fluxes and enzyme capacities together revealed stage
dependent features. Cell division was characterized by a high sucrolytic activity
of the vacuole, whereas sucrose cleavage during expansion was sustained by both
sucrose synthase and neutral invertase, associated with minimal futile cycling.
Most importantly, a tight correlation between flux rate and enzyme capacity was
found for fructokinase and PPi-dependent phosphofructokinase during cell division
and for sucrose synthase, UDP-glucopyrophosphorylase, and phosphoglucomutase
during expansion, thus suggesting an adaptation of enzyme abundance to metabolic
needs. In contrast, for most enzymes, flux rates varied irrespectively of enzyme
capacities, and most enzymes functioned at <5% of their maximal catalytic
capacity. One of the major findings with the model was the high accumulation of
soluble sugars within the vacuole together with organic acids, thus enabling the
osmotic-driven vacuole expansion that was found during cell division.
PMID- 25139006
TI - Functional characterization of the small regulatory subunit PetP from the
cytochrome b6f complex in Thermosynechococcus elongatus.
AB - The cyanobacterial cytochrome b(6)f complex is central for the coordination of
photosynthetic and respiratory electron transport and also for the balance
between linear and cyclic electron transport. The development of a purification
strategy for a highly active dimeric b(6)f complex from the thermophilic
cyanobacterium Thermosynechococcus elongatus BP-1 enabled characterization of the
structural and functional role of the small subunit PetP in this complex.
Moreover, the efficient transformability of this strain allowed the generation of
a DeltapetP mutant. Analysis on the whole-cell level by growth curves,
photosystem II light saturation curves, and P700(+) reduction kinetics indicate a
strong decrease in the linear electron transport in the mutant strain versus the
wild type, while the cyclic electron transport via photosystem I and cytochrome
b(6)f is largely unaffected. This reduction in linear electron transport is
accompanied by a strongly decreased stability and activity of the isolated
DeltapetP complex in comparison with the dimeric wild-type complex, which binds
two PetP subunits. The distinct behavior of linear and cyclic electron transport
may suggest the presence of two distinguishable pools of cytochrome b(6)f
complexes with different functions that might be correlated with supercomplex
formation.
PMID- 25139007
TI - A mitogen-activated protein kinase cascade module, MKK3-MPK6 and MYC2, is
involved in blue light-mediated seedling development in Arabidopsis.
AB - Mitogen-activated protein kinase (MAPK) pathways are involved in several signal
transduction processes in eukaryotes. Light signal transduction pathways have
been extensively studied in plants; however, the connection between MAPK and
light signaling pathways is currently unknown. Here, we show that MKK3-MPK6 is
activated by blue light in a MYC2-dependent manner. MPK6 physically interacts
with and phosphorylates a basic helix-loop-helix transcription factor, MYC2, and
is phosphorylated by a MAPK kinase, MKK3. Furthermore, MYC2 binds to the MPK6
promoter and regulates its expression in a feedback regulatory mechanism in blue
light signaling. We present mutational and physiological studies that illustrate
the function of the MKK3-MPK6-MYC2 module in Arabidopsis thaliana seedling
development and provide a revised mechanistic view of photomorphogenesis.
PMID- 25139008
TI - Riluzole likely lacks antidepressant efficacy in ketamine non-responders.
PMID- 25139010
TI - Pertussis in Latin America: epidemiology and control strategies.
AB - Pertussis is a serious respiratory disease in infants that can also affect
children and adults. Vaccination against pertussis was introduced in the 1950s
and in the 1990s a resurgence of pertussis was observed worldwide. The aim of
this work is to summarize the recent data concerning pertussis disease in
different countries of Latin America. In this geographic region, pertussis is
nationally notifiable and cases should be reported to the appropriate health
department/Ministry. Though the surveillance systems are not the same among Latin
America countries, over recent decades an increasing number of cases have been
detected. Most of these cases correspond to patients younger than 6 months old
who received fewer than three doses of vaccine. However, cases in adolescent and
adults have also been detected. For this situation, which is not peculiar to
Latin America countries, several explanations have been proposed.
PMID- 25139011
TI - Validation of a web-based questionnaire to assess the dietary intake of Brazilian
children aged 7-10 years.
AB - BACKGROUND: The Food Intake and Physical Activity of School Children (CAAFE)
comprises an online questionnaire to self-report diet and physical activity of
Brazilian schoolchildren. BACKGROUND: The present study aimed to assess the
validity (matches, omissions and intrusions) and moderating factors of the CAAFE.
METHODS: Direct observation was made of foods consumed (five public schools) and
child self-reporting on the CAAFE. Additional data included school grade, gender,
body mass index, completion of food diary, socioeconomic status and access to
computer. Data were analysed using regression. RESULTS: In total, 602 children
participated in the study [mean (SD) age 9.5 (1.24) years; 53.6% boys]. On
average, there were 43% matches, 29% intrusions and 28% omissions. Matches
doubled in third grade compared to the second grade (P = 0.004); matches almost
tripled for afternoon snack compared to morning snack (P < 0.001); and matches
were 69% higher for children with access to a computer at home (P < 0.01).
Intrusions decreased by almost one-half in fifth compared to fourth grades (P =
0.004). Omissions declined significantly in the third and fourth grades but
increased in the fifth grade. Omissions were 47% lower for children in the
highest income and lower among children who completed the food diary. No
differences were found for gender or body mass index. CONCLUSIONS: Children older
than 8 years old, who owned a computer and completed a food diary, performed
better in the CAAFE. A high incidence of disagreement was found in relation to
the schools and the type of meal. Overall matches (43%), intrusions (29%) and
omissions (28%) indicate that further studies are required to improve the
validity of the CAAFE.
PMID- 25139009
TI - The cumulative effect of different childhood trauma types on self-reported
symptoms of adult male depression and PTSD, substance abuse and health-related
quality of life in a large active-duty military cohort.
AB - History of childhood trauma (CT) is highly prevalent and may lead to long-term
consequences on physical and mental health. This study investigated the
independent association of CT with symptoms of adult depression and posttraumatic
stress disorder (PTSD), mental and physical health-related quality of life
(HRQoL), as well as current tobacco consumption and alcohol abuse in a large
homogenous cohort of 1254 never-deployed, young male Marines enrolled in the
Marine Resiliency Study. Independent effects of CT history, number and type of CT
on outcomes were analyzed using hierarchical multivariate logistic regression
models. Our results suggested dose-dependent negative effect of an increasing
number of trauma types of CT on depression, PTSD and HRQoL. Experience of single
CT type demonstrated overall weak effects, while history of multiple CT types
distinctively increased the likelihood of adult PTSD symptomology (OR: 3.1, 95%
CI: 1.5-6.2), poor mental (OR: 2.3, 95% CI: 1.7-3.1) and physical HRQoL (OR: 1.4,
95% CI: 1.1-1.9). Risk for depression symptoms was similar for both single and
multiple CT (OR: 2.2, 95% CI: 1.3-3.8 and OR: 2.1, 95% CI: 1.2-3.5 respectively).
CT history had no effects on current tobacco use and alcohol abuse. Our study
thus provides evidence for substantial additive effect of different CT types on
adult mental and physical health with increasing levels of exposure.
PMID- 25139013
TI - Enhanced resistance of CXCR3 deficient mice to ocular HSV-1 infection is due to
control of replication in the brain ependyma.
AB - CXCR3 deficient (CXCR3(-/-)) mice are resistant to ocular HSV-1 infection in that
less mice develop encephalitis and succumb to infection in comparison to wild
type (WT) animals. A region of the brain previously identified to be crucial for
development of encephalitis was evaluated in HSV-1-infected CXCR3(-/-) and WT
mice. In this region, known as the ependyma, viral titer, infiltrating leukocyte
populations, and key anti-viral cytokine message levels were evaluated. We found
that CXCR3(-/-) mice possessed significantly less HSV-1 and expressed
significantly more IFN-beta mRNA in the brain ependyma compared to WT animals
during the development of encephalitis.
PMID- 25139014
TI - Immunosuppressants increase the levels of natural autoantibodies reactive with
glycosaminoglycans in myasthenia gravis.
AB - Increasing number of evidences support the role of glycosylation in the evolution
of autoimmunity. We examined carbohydrate-reactive natural autoantibodies
systematically for the first time in patients with autoimmune myasthenia gravis.
Antibodies reactive to glycosaminoglycans were measured with CovaLink ELISA in
the sera of 59 myasthenia patients as well as in 54 healthy controls. We used the
GlycoChip carbohydrate array to characterize individual carbohydrate recognition
patterns. Chondroitin-sulphate C and anti-alpha-mannose-specific IgG levels were
significantly elevated in myasthenia patients. Unexpectedly, we found that
immunosuppressants increased the levels of the protective IgM glycosaminoglycan
reactive natural antibodies demonstrating a new role for these agents in
immunoregulation.
PMID- 25139015
TI - Comparison of computed tomographic and pathologic findings in 17 dogs with
primary adrenal neoplasia.
AB - The CT appearance of canine adrenal masses has been reported, but associations
between imaging features and pathologic features of these lesions have not been
investigated in detail. The purpose of this study was to test associations
between different types of adrenal neoplasia and their CT and pathologic
features. A retrospective cross-sectional study was performed and inclusion
criteria were histologic diagnosis of primary adrenal neoplasia, contrast
enhanced CT examination of the abdomen and surgical resection of the mass or
necropsy examination. For all included dogs, CT images and histopathologic
specimens were reviewed independently by two veterinary radiologists and a
veterinary pathologist, respectively. Seventeen dogs met inclusion criteria.
Diagnoses were adenocarcinoma in nine (53%) dogs, pheochromocytoma in five (29%)
dogs, and adenoma in three (18%) dogs. Pheochromocytoma was associated with CT
signs of vascular invasion (likelihood ratio = 4.8, 95% CI = 1.3-18.3, P = 0.03)
and macroscopic vascular invasion (likelihood ratio = 9.6, 95% CI = 1.4-65.9, P =
0.02). There was excellent agreement between signs of vascular invasion in CT
images and vascular invasion at surgery or necropsy (kappa = 0.86, P = 0.001). A
peripheral contrast-enhancing rim in delayed postcontrast CT images was
associated with fibrous encapsulation of the tumor (kappa = 0.53, P = 0.05), and
a heterogeneous pattern of contrast distribution in delayed postcontrast CT
images was associated with adrenal hemorrhage or infarction on histological
examination (kappa = 0.45, P = 0.05). Findings indicated that CT enabled
assessment of adrenal neoplasia features that reflected their biological behavior
and pathological findings, however overlapping characteristics between tumor
types limited the potential for reliably distinguishing them based on CT alone.
PMID- 25139016
TI - Intermediate monocytes contribute to pathologic immune response in Leishmania
braziliensis infections.
AB - Ulcer development in patients with cutaneous leishmaniasis (CL) caused by
Leishmania braziliensis is associated with high levels of tumor necrosis factor
(TNF). We found that early after infection, before ulcer development, the
frequency of CD16(+) (both intermediate [CD14(+)CD16(+)] and nonclassical
[CD14(dim)CD16(+)]) monocytes was increased in the peripheral blood of patients
with L. braziliensis, compared with uninfected controls. These results suggest
that CD16(+) monocytes might promote disease. Also, we found that intermediate
monocytes expressed CCR2 and that increased levels of CCL2 protein were present
in lesions from patients, suggesting that intermediate monocytes are more likely
than nonclassical monocytes to migrate to the lesion site. Finally, we found that
the intermediate monocytes produced TNF. Our results show that intermediate
monocytes are increased in frequency soon after infection; express CCR2, which
would promote their migration into the lesions; and, owing to their production of
TNF, can enhance the inflammatory response.
PMID- 25139017
TI - Probing of a human proteome microarray with a recombinant pathogen protein
reveals a novel mechanism by which hookworms suppress B-cell receptor signaling.
AB - Na-ASP-2 is an efficacious hookworm vaccine antigen. However, despite elucidation
of its crystal structure and studies addressing its immunobiology, the function
of Na-ASP-2 has remained elusive. We probed a 9000-protein human proteome
microarray with Na-ASP-2 and showed binding to CD79A, a component of the B-cell
antigen receptor complex. Na-ASP-2 bound to human B lymphocytes ex vivo and
downregulated the transcription of approximately 1000 B-cell messenger RNAs
(mRNAs), while only approximately 100 mRNAs were upregulated, compared with
control-treated cells. The expression of a range of molecules was affected by Na
ASP-2, including factors involved in leukocyte transendothelial migration
pathways and the B-cell signaling receptor pathway. Of note was the downregulated
transcription of lyn and pi3k, molecules that are known to interact with CD79A
and control B-cell receptor signaling processes. Together, these results
highlight a previously unknown interaction between a hookworm-secreted protein
and B cells, which has implications for helminth-driven immunomodulation and
vaccine development. Further, the novel use of human protein microarrays to
identify host-pathogen interactions, coupled with ex vivo binding studies and
subsequent analyses of global gene expression in human host cells, demonstrates a
new pipeline by which to explore the molecular basis of infectious diseases.
PMID- 25139019
TI - Dietary pectin-derived acidic oligosaccharides improve the pulmonary bacterial
clearance of Pseudomonas aeruginosa lung infection in mice by modulating
intestinal microbiota and immunity.
AB - BACKGROUND: A predominantly T-helper type 2 (Th2) immune response is critical in
the prognosis of pulmonary Pseudomonas aeruginosa infection. But the mucosal and
systemic immune responses can be influenced by the intestinal microbiota.
METHODS: We assessed the effect of microbiota compositional changes induced by a
diet enriched in 5% acidic oligosaccharides derived from pectin (pAOS) on the
immune response and outcome of chronic pulmonary P. aeruginosa infection in mice.
RESULTS: pAOS promoted Th1 polarization by increasing interferon gamma release,
upregulating t-bet gene expression, decreasing interleukin 4 secretion, and
downregulating gata3 gene expression. pAOS also sustained the release of
keratinocyte chemoattractant, recruited polynuclear leukocytes and macrophages,
stimulated M1 macrophage activation and interleukin 10 release, and decreased
tumor necrosis factor alpha release in the lung. These effects led to increased
bacterial clearance after the first and second P. aeruginosa infections. pAOS
modified the intestinal microbiota by stimulating the growth of species involved
in immunity development, such as Bifidobacterium species, Sutturella wadsworthia,
and Clostridium cluster XIVa organisms, and at the same time increased the
production of butyrate and propionate. CONCLUSION: These results suggest that
pAOS may have beneficial effects by limiting the number and severity of pulmonary
exacerbations in patients chronically infected with P. aeruginosa, such as
individuals with cystic fibrosis.
PMID- 25139018
TI - Human papillomavirus 16-specific T-cell responses and spontaneous regression of
anal high-grade squamous intraepithelial lesions.
AB - BACKGROUND: Most anal cancers are attributable to persistent human papillomavirus
type 16 (HPV-16) infection. The anal cancer precursor, high-grade squamous
intraepithelial lesion (HSIL), frequently regresses spontaneously. We
hypothesized that T-cell responses are associated with HSIL regression. METHODS:
In men who have sex with men undergoing anal cytology and high-resolution
anoscopy, we measured responses to HPV-16 oncogenic proteins E6 and E7, using the
CD25/CD134 assay for CD4(+) antigen-specific T cells and intracellular cytokine
staining for CD4(+) and CD8(+) antigen-specific T cells. RESULTS: Of 134
participants (mean [SD] age, 51 [9.3] years; 31 [23.1%] infected with human
immunodeficiency virus), 51 (38.1%) had HSIL. E6- and E7-specific CD4(+) T-cell
responses were detected in 80 (59.7%) and 40 (29.9%) of the participants,
respectively, and E6- and E7-specific CD8(+) T-cell responses were each detected
in 25 (18.7%). HSIL was significantly associated with E7-specific CD8(+) T-cell
responses (odds ratio, 4.09 [95% confidence interval, 1.55-10.77], P = .004), but
not with any CD4(+) T-cell response (P >= .09). Twenty-six participants had HSIL
a mean of 1 year before measurement of T-cell responses, and 6 (23%) of them were
regressors. Five regressors (83%) had E6-specific CD4(+) T-cell responses vs 7 of
20 (35%) nonregressors (Pexact = .065). CONCLUSIONS: Systemic HPV-16 E6- and E7
specific T-cell responses were common in men who have sex with men. E6-specific
CD4(+) T-cell responses may be associated with recent HSIL regression. CLINICAL
TRIALS REGISTRATION: NCT02007421.
PMID- 25139020
TI - BB0323 and novel virulence determinant BB0238: Borrelia burgdorferi proteins that
interact with and stabilize each other and are critical for infectivity.
AB - We have shown that Borrelia burgdorferi gene product BB0323 is essential for cell
fission and pathogen persistence in vivo. Here we describe characterization of a
conserved hypothetical protein annotated as BB0238, which specifically interacts
with the N-terminal region of BB0323. We show that BB0238 is a subsurface
protein, and similar to BB0323, exists in the periplasm and as a membrane-bound
protein. Deletion of bb0238 in infectious B. burgdorferi did not affect microbial
growth in vitro or survival in ticks, but the mutant was unable to persist in
mice or transmit from ticks--defects that are restored on genetic
complementation. Remarkably, BB0238 and BB0323 contribute to mutual
posttranslational stability, because deletion of one causes dramatic reduction in
the protein level of the other partner. Interference with the function of BB0238
or BB0323 and their interaction may provide novel strategies to combat B.
burgdorferi infection.
PMID- 25139021
TI - Basis of virulence in a Panton-Valentine leukocidin-negative community-associated
methicillin-resistant Staphylococcus aureus strain.
AB - Community-associated (CA) infections with methicillin-resistant Staphylococcus
aureus (MRSA) are on a global rise. However, analysis of virulence
characteristics has been limited almost exclusively to the US endemic strain
USA300. CA-MRSA strains that do not produce Panton-Valentine leukocidin (PVL)
have not been investigated on a molecular level. Therefore, we analyzed virulence
determinants in a PVL-negative CA-MRSA strain, ST72, from Korea. Genome-wide
analysis identified 3 loci that are unique to that strain, but did not affect
virulence. In contrast, phenol-soluble modulins (PSMs) and the global virulence
regulator Agr strongly affected lysis of neutrophils and erythrocytes, while
alpha-toxin and Agr had a major impact on in vivo virulence. Our findings
substantiate the general key roles these factors play in CA-MRSA virulence.
However, our analyses also showed noticeable differences to strain USA300,
inasmuch as alpha-toxin emerged as a much more important factor than PSMs in
experimental skin infection caused by ST72.
PMID- 25139022
TI - Tr-1-like CD4+CD25-CD127-/lowFOXP3- cells are the main source of interleukin 10
in patients with cutaneous leishmaniasis due to Leishmania braziliensis.
AB - CD4(+)CD25(+)FOXP3(+) regulatory T cells have long been shown to mediate
susceptibility to Leishmania infection, mainly via interleukin 10 production. In
this work, we showed that the main sources of interleukin 10 in peripheral blood
mononuclear cells (PBMCs) from patients with cutaneous leishmaniasis due to
Leishmania braziliensis are CD4(+)CD25(-)CD127(-/low)FOXP3(-) cells. Compared
with uninfected controls, patients with CL had increased frequencies of
circulating interleukin 10-producing CD4(+)CD25(-)CD127(-/low) cells, which
efficiently suppressed tumor necrosis factor alpha production by the total PBMC
population. Also, in CL lesions, interleukin 10 was mainly produced by
CD4(+)CD25(-) cells, and interleukin 10 messenger RNA expression was associated
with interleukin 27, interleukin 21, and interferon gamma expression, rather than
with FOXP3 or transforming growth factor beta expressions. Active production of
both interleukin 27 and interleukin 21, together with production of interferon
gamma and interleukin 10, was also detected in the lesions. Since these cytokines
are associated with the differentiation and activity of Tr-1 cells, our results
suggest that this cell population may play an important role in the
immunomodulation of CL. Therefore, development of treatments that interfere with
this pathway may lead to faster parasite elimination.
PMID- 25139023
TI - Fetal origins of malarial disease: cord blood cytokines as risk markers for
pediatric severe malarial anemia.
AB - BACKGROUND: Severe malarial anemia (SMA) remains a major cause of pediatric
illness and mortality in Sub-Saharan Africa. Here we test the hypothesis that
prenatal exposures, reflected by soluble inflammatory mediators in cord blood,
can condition an individual's susceptibility to SMA. METHODS: In a Tanzanian
birth cohort (n = 743), we measured cord blood concentrations of tumor necrosis
factor (TNF), TNF receptors I and II (TNF-RI and TNF-RII), interleukin (IL)
1beta, IL-4, IL-5, IL-6, IL-10, and interferon gamma (IFN-gamma). After adjusting
for conventional covariates, we calculated the hazard ratios (HR) for time to
first SMA event with log(e) cytokine concentrations dichotomized at the median,
by quartile, and per standard deviation (SD) increase. RESULTS: Low levels of
TNF, TNF-RI, IL-1beta, and IL-5 and high levels of TNF-RII were associated
statistically significantly and respectively with approximately 3-fold, 2-fold, 8
fold, 4-fold, and 3-fold increased risks of SMA (Hb < 50 g/L). TNF, TNF-RI, and
IL-1beta concentrations were inversely and log-linearly associated with SMA risk;
the HR (95% confidence interval [CI]) per 1-SD increase were respectively 0.81
(.65, 1.02), 0.76 (.62, .92), and 0.50 (.40, .62). CONCLUSIONS: These data
suggest that proinflammatory cytokine levels at birth are inversely associated
with SMA risk and support the hypothesis that pediatric malarial disease has
fetal origins.
PMID- 25139024
TI - MiR-136 targets E2F1 to reverse cisplatin chemosensitivity in glioma cells.
AB - MicroRNAs (miRNAs) have gained much attention due to their critical roles in
diverse biological events, including tumorigenesis. In this study, we demonstrate
that miR-136 is down-regulated in two cohorts of patients with glioma.
Furthermore, the low-level expression of miR-136 is significantly associated with
a more aggressive and/or poor prognostic phenotype of patients with gliomas. Both
gain- and loss-of-function experiments showed that miR-136 expression can reverse
cisplatin resistance and enhance the response to cisplatin treatment.
Furthermore, we identified a novel direct target of miR-136, the E2F
transcription factor 1 (E2F1) oncogene. Depletion of E2F1 recapitulated the tumor
suppressive functions of miR-136, whereas re-expression of E2F1 attenuated the
function of miR-136 in glioma cells. Finally, we revealed that miR-136 is
inversely correlated with E2F1 expression in human glioma samples. The present
study provides functional and mechanistic links between the tumor suppressor miR
136 and the oncogene E2F1 for the development of chemoresistance in human glioma.
Our results indicate that targeting of the miR-136/E2F1 axis may provide a
promising therapeutic approach to treat glioma.
PMID- 25139026
TI - Temozolomide after radiotherapy in recurrent "low grade" diffuse brainstem glioma
in adults.
AB - Diffuse brainstem glioma is a rare disease in adults. Radiotherapy (RT) is
usually considered to be the standard treatment. However, the role of
chemotherapy in treating relapses after RT is unclear, and this study aimed to
assess the use of temozolomide (TMZ) in this situation. We conducted a
retrospective analysis of patients from our database with "low grade" adult
diffuse infiltrating brainstem glioma who received TMZ at relapse after failing
RT. The patients were diagnosed by histology or MRI criteria compatible with a
low-grade glioma. The tumors were localized in the pons, medulla oblongata or
midbrain, excluding supratentorial or infratentorial tumors that had infiltrated
the brainstem secondarily. The patients' clinical and radiological responses were
assessed, and their progression free survival (PFS) and overall survival (OS)
time were estimated. Fifteen adult patients (median age 34 years) fulfilled the
inclusion criteria. Histological analysis was available in 5 cases and showed
grade II oligodendroglioma (2 cases), grade II oligoastrocytoma (2 cases), and
grade II astrocytoma (1 case). Ten patients were selected by MRI criteria only.
All patients received RT as initial treatment and had a median PFS of 34.2 months
(95 % CI 24.1-44.2). The median KPS at the time of relapse was 80. TMZ was
administered orally at 150-200 mg/m(2) for 5 days, every 28 days. Clinical
improvement after TMZ was observed in 9 cases (60 %), whereas radiological
assessment detected responses in 6/15 cases, including 4 partial and 2 minor
responses. The estimated median PFS after TMZ was 9.5 months (95 % CI 7.9-11),
and the median OS was 14.4 months (95 % CI 10.5-18.2). Grade 3 thrombopenia was
observed in 26 % of cases. TMZ could be useful after RT failure in adult patients
with recurrent diffuse "low grade" brainstem glioma.
PMID- 25139025
TI - Co-administration of ABT-737 and SAHA induces apoptosis, mediated by Noxa
upregulation, Bax activation and mitochondrial dysfunction in PTEN-intact
malignant human glioma cell lines.
AB - We previously observed that glioma cells are differentially sensitive to ABT-737
and, when used as a single-agent, this drug failed to induce apoptosis.
Identification of therapeutic strategies to enhance the efficacy of the Bcl-2
inhibitor ABT-737 in human glioma is of interest. Histone deacetylation
inhibitors (HDACI) are currently being assessed clinically in patients with
glioma, as regulation of epigenetic abnormalities is expected to produce pro
apoptotic effects. We hypothesized that co-treatment of glioma with a BH3-mimetic
and HDACI may induce cellular death. We assessed the combination of ABT-737 and
HDACI SAHA in established and primary cultured glioma cells. We found combination
treatment led to significant cellular death when compared to either drug as
single agent and demonstrated activation of the caspase cascade. This enhanced
apoptosis also appears dependent upon the loss of mitochondrial membrane
potential and the release of cytochrome c and AIF into the cytosol. The
upregulation of Noxa, truncation of Bid, and activation of Bax caused by this
combination were important factors for cell death and the increased levels of
Noxa functioned to sequester Mcl-1. This combination was less effective in PTEN
deficient glioma cells. Both genetic and pharmacologic inactivation of the
PI3K/Akt signaling pathway sensitized PTEN-deleted glioma cells to the
combination. This study demonstrates that antagonizing apoptosis-resistance
pathways, such as targeting the Bcl-2 family in combination with epigenetic
modifiers, may induce cell death. These findings extend our previous observations
that targeting the PI3K/Akt pathway may be additionally necessary to promote
apoptosis in cancers lacking PTEN functionality.
PMID- 25139027
TI - Sequencing and de novo assembly of the red cusk-eel (Genypterus chilensis)
transcriptome.
AB - The red cusk-eel (Genypterus chilensis) is an endemic fish species distributed
along the coasts of the Eastern South Pacific. Biological studies on this fish
are scarce, and genomic information for G. chilensis is practically non-existent.
Thus, transcriptome information for this species is an essential resource that
will greatly enrich molecular information and benefit future studies of red cusk
eel biology. In this work, we obtained transcriptome information of G. chilensis
using the Illumina platform. The RNA sequencing generated 66,307,362 and
59,925,554 paired-end reads from skeletal muscle and liver tissues, respectively.
De novo assembly using the CLC Genomic Workbench version 7.0.3 produced 48,480
contigs and created a reference transcriptome with a N50 of 846bp and average
read coverage of 28.3*. By sequence similarity search for known proteins, a total
of 21,272 (43.9%) contigs were annotated for their function. Out of these
annotated contigs, 33.5% GO annotation results for biological processes, 32.6% GO
annotation results for cellular components and 34.5% GO annotation results for
molecular functions. This dataset represents the first transcriptomic resource
for the red cusk-eel and for a member of the Ophidiimorpharia taxon.
PMID- 25139028
TI - Bioaccumulation and toxicity of silver nanoparticles and silver nitrate to the
soil arthropod Folsomia candida.
AB - The growing use of silver nanoparticles (Ag-NP) triggered an increasing interest
in their environmental fate and possible ecotoxicological impacts. To investigate
the potential risk of Ag-NP to soil organisms, the springtail Folsomia candida
was exposed to Ag-NP (reported diameter size 3-8 nm) and AgNO3 in Lufa 2.2
natural soil for 28 days to determine effects on survival and reproduction. Also,
the kinetics of uptake and elimination of Ag were studied for F. candida exposed
in Lufa 2.2 soil to Ag-NP (at 168 mg Ag/kg dry soil) and AgNO3 (at 30 and 60 mg
Ag/kg dry soil). AgNO3 was toxic with an LC50 was 284 mg Ag/kg dry soil for
effects on survival and EC10 and EC50 values of 47.6 and 99.5 mg Ag/kg dry soil,
respectively for the effect on reproduction. These values did correspond with
porewater concentrations of 0.801, 0.042 and 0.082 mg Ag/l, respectively. No
effects on survival and reproduction of Ag-NP were observed up to 673 mg Ag/kg
dry soil, although porewater concentration was similar to the EC50 for AgNO3.
Exposure to both Ag forms caused a fast uptake of Ag, but the Ag elimination rate
was significantly higher for Ag-NP than for AgNO3. Bioaccumulation factor was
higher for AgNO3 (on average 5.64) than for Ag-NP (1.12). These findings indicate
that silver ions are more toxic than Ag-NP and have a higher potential to
accumulate in F. candida.
PMID- 25139029
TI - Aquatic environmental safety assessment and inhibition mechanism of chemicals for
targeting Microcystis aeruginosa.
AB - Cyanobacteria are a diverse group of Gram-negative bacteria that produce an array
of secondary compounds with selective bioactivity against vertebrates,
invertebrates, fungi, bacteria and cell lines. Recently the main methods of
controlling cyanobacteria are using chemicals, medicinal plants and microorganism
but fewer involved the safety research in hydrophytic ecosystems. In search of an
environmentally safe compound, 53 chemicals were screened against the developed
heavy cyanobacteria bloom Microcystis aeruginosa using coexistence culture system
assay. The results of the coexistence assay showed that 9 chemicals inhibited M.
aeruginosa effectively at 20 mg L(-1) after 7 days of exposure. Among them
dimethomorph, propineb, and paraquat were identified that they are safe for
Chlorella vulgaris, Scenedesmus obliquus, Carassius auratus (Goldfish) and
Bacillus subtilis within half maximal effective concentration (EC50) values 5.2,
4.2 and 0.06 mg L(-1) after 7 days, respectively. Paraquat as the positive
control observed to be more efficient than the other compounds with the
inhibitory rate (IR) of 92% at 0.5 mg L(-1). For the potential inhibition
mechanism, the chemicals could destroy the cell ultrastructure in different
speed. The safety assay proved dimethomorph, propineb and paraquat as harmless
formulations or products having potential value in M. aeruginosa controlling,
with the advantage of its cell morphology degrading ability.
PMID- 25139031
TI - Investigation on bacterial community and diversity in the multilayer aquifer
aquitard system of the Pearl River Delta, China.
AB - Bacteria play an important role in groundwater chemistry. The groundwater
resource in the Pearl River Delta (PRD) is responsible for 50 million people's
water requirement. High amount of ammonium, arsenic and methane had been reported
in groundwater of the PRD, which was considered as the result of intensive
bacterial metabolism in the multilayer aquifer-aquitard system. To investigate
bacterial community in this system and its relation with groundwater chemistry,
sediment and groundwater samples were taken from representative locations in the
PRD at different lithological units. Bacterial 16S rRNA gene clone libraries were
constructed for microbial identifications and community structures in different
strata. Canonical correlation analysis between bacterial linages and environment
variables (Cl(-), PO4(3-), SO4(2-), NH4(+)) showed that community structures were
significantly modified by geological conditions. Higher bacterial diversity was
observed in samples from the Holocene aquitard M1 and aquifer T1, while in the
older aquitard M2 and basal aquifer T2, bacterial diversity was much lower.
Chloroflexi, gamma-proteobacteria and delta-proteobacteria were the dominant
phyla in the aquitard sediment. beta-proteobacteria was the dominant phylum in
sediment which was strongly influenced by fresh water. The results of this study
demonstrated that bacterial community contains information of geological events
such as sea transgression and deltaic evolution, and microbes in the aquitards
have great potential in dominating groundwater quality in aquifers.
PMID- 25139030
TI - Modification of the brain proteome of Africanized honeybees (Apis mellifera)
exposed to a sub-lethal doses of the insecticide fipronil.
AB - Fipronil is a phenylpyrazole insecticide that is widely used in Brazilian
agriculture for pest control. Although honeybees are not targets of fipronil,
studies indicate that this pesticide can be harmful to honeybees. To assess the
effects of fipronil in the brain of Africanized Apis mellifera workers, this
study focused on the toxico-proteome profiling of the brain of newly emerged and
aged honeybee workers that were exposed to a sub-lethal dose (10 pg fipronil per
day. i.e. (1)/100 of LD50/bee/day during 5 days) of the insecticide. Proteomic
analysis identified 25 proteins that were differentially up-regulated or down
regulated when the fipronil-exposed and non-exposed groups were compared. These
proteins are potentially related to pathogen susceptibility, neuronal chemical
stress, neuronal protein misfolding, and occurrence of apoptosis, ischemia,
visual impairment, damaged synapse formation, brain degeneration, memory and
learning impairment. The exposure of honeybees to a very low dose of fipronil,
even for a short period of time (5 days), was sufficient to cause a series of
important neuroproteomic changes in the brains of honeybees.
PMID- 25139032
TI - Perchlorate-induced oxidative stress in isolated liver mitochondria.
AB - As a new threat to environment all through the world, perchlorate (ClO4(-)) was
predominantly a thyrotoxin, and its toxic manifestations in non-thyroid were also
documented. To date, little is known about the effect of ClO4(-) on cell and
organelle. To reveal the toxicity of ClO4(-) on living organism in-depth,
mitochondria isolated from liver of Carassius auratus were incubated with
different concentrations of ClO4(-). The results demonstrated that ClO4(-)
induced mitochondrial oxidative stress, and subsequently caused a gradual opening
of permeability transition pore leading to mitochondrial swelling and lipid
peroxidative membrane damage. ClO4(-) has a conspicuous inhibition of electron
transport chain activity which largely correlated to complexes I and IV. The
investigations clearly demonstrated the oxidative stress of ClO4(-) in
mitochondria, may well reveal cytotoxic effects in vitro that merit further
investigation.
PMID- 25139033
TI - Arsenic release from shallow aquifers of the Hetao basin, Inner Mongolia:
evidence from bacterial community in aquifer sediments and groundwater.
AB - Indigenous microbes play crucial roles in arsenic mobilization in high arsenic
groundwater systems. Databases concerning the presence and the activity of
microbial communities are very useful in evaluating the potential of microbe
mediated arsenic mobilization in shallow aquifers hosting high arsenic
groundwater. This study characterized microbial communities in groundwaters at
different depths with different arsenic concentrations by DGGE and one sediment
by 16S rRNA gene clone library, and evaluated arsenic mobilization in microcosm
batches with the presence of indigenous bacteria. DGGE fingerprints revealed that
the community structure changed substantially with depth at the same location. It
indicated that a relatively higher bacterial diversity was present in the
groundwater sample with lower arsenic concentration. Sequence analysis of 16S
rRNA gene demonstrated that the sediment bacteria mainly belonged to Pseudomonas,
Dietzia and Rhodococcus, which have been widely found in aquifer systems.
Additionally, NO3(-)-reducing bacteria Pseudomonas sp. was the largest group,
followed by Fe(III)-reducing, SO4(2-)-reducing and As(V)-reducing bacteria in the
sediment sample. These anaerobic bacteria used the specific oxyanions as electron
acceptor and played a significant role in reductive dissolution of Fe oxide
minerals, reduction of As(V), and release of arsenic from sediments into
groundwater. Microcosm experiments, using intact aquifer sediments, showed that
arsenic release and Fe(III) reduction were microbially mediated in the presence
of indigenous bacteria. High arsenic concentration was also observed in the batch
without amendment of organic carbon, demonstrating that the natural organic
matter in sediments was the potential electron donor for microbially mediated
arsenic release from these aquifer sediments.
PMID- 25139034
TI - The source apportionment of polycyclic aromatic hydrocarbons (PAHs) in the
topsoil in Xiaodian sewage irrigation area, North of China.
AB - 31 topsoil samples were collected by grid method in Xiaodian sewage irrigation
area, Taiyuan City, North of China. The concentrations of 16 kinds of polycyclic
aromatic hydrocarbons (PAHs) were determined by gas chromatograph coupled with
mass spectrum. Generally speaking, the distribution order of PAHs in the area is:
those with five and six rings > those with four rings > those with two and three
rings. Source apportionment shows a significant zonation of the source of PAHs:
the civil coal pollution occurred in the north part, the local and far factory
pollution happened in the middle area and the mixed pollution sources from coal
and wood combustion, automotive emission, presented in the south area. The
distribution of PAHs has a definite relationship with the sewage water flow and
soil adsorption. The related coefficient between PAHs and physicochemical
property showed there was a negative correlation between pH, silt, clay and PAHs
while there was a positive correlation between total organic carbon, sand and
PAHs.
PMID- 25139036
TI - Designing systematic and center-specific metrics to foster innovation.
PMID- 25139037
TI - Bladder volume estimation from electrical impedance tomography.
AB - Non-invasive estimation of bladder volume is required to progress from scheduled
voiding to a demand-driven emptying scheme for patients with impaired bladder
volume sensation. Electrical impedance tomography (EIT) is a promising candidate
for the non-invasive monitoring of bladder volume. This article focuses on four
estimation algorithms used to map recorded EIT data to a volume estimate. Two
different approaches are presented: the tomographic algorithms (one based on
global impedance, the other on equivalent circular diameter) rely on the
reconstruction of a tomographic image and then extract a volume estimate, whereas
the parametric algorithms (one based on neural networks, the other on the
singular value difference method) directly map the raw data to a volume estimate.
The four algorithms presented here are evaluated for volume estimation error,
noise tolerance and suppression of varying urine conductivity based on finite
element simulation data.
PMID- 25139035
TI - Distribution patterns of ammonia-oxidizing bacteria and anammox bacteria in the
freshwater marsh of Honghe wetland in Northeast China.
AB - Community characteristics of aerobic ammonia-oxidizing bacteria (AOB) and
anaerobic ammonium-oxidizing (anammox) bacteria in Honghe freshwater marsh, a
Ramsar-designated wetland in Northeast China, were analyzed in this study.
Samples were collected from surface and low layers of sediments in the
Experimental, Buffer, and Core Zones in the reserve. Community structures of AOB
were investigated using both 16S rRNA and amoA (encoding for the alpha-subunit of
the ammonia monooxygenase) genes. Majority of both 16S rRNA and amoA gene-PCR
amplified sequences obtained from the samples in the three zones affiliated with
Nitrosospira, which agreed with other wetland studies. A relatively high richness
of beta-AOB amoA gene detected in the freshwater marsh might suggest minimal
external pressure was experienced, providing a suitable habitat for beta-AOB
communities. Anammox bacteria communities were assessed using both 16S rRNA and
hzo (encoding for hydrazine oxidoreductase) genes. However, PCR amplification of
the hzo gene in all samples failed, suggesting that the utilization of hzo
biomarker for detecting anammox bacteria in freshwater marsh might have serious
limitations. Results with 16S rRNA gene showed that Candidatus Kuenenia was
detected in only the Experimental Zone, whereas Ca. Scalindua including different
lineages was observed in both the Buffer and Experimental Zones but not the Core
Zone. These results indicated that both AOB and anammox bacteria have specific
distribution patterns in the ecosystem corresponding to the extent of
anthropogenic impact.
PMID- 25139039
TI - If groundwater is contaminated, will water from the well be contaminated?
PMID- 25139038
TI - Balance of antiangiogenic and angiogenic factors in the context of the etiology
of preeclampsia.
AB - The "two-stage disorder" theory that is assumed for the etiology of preeclampsia
hypothesizes that antiangiogenic and angiogenic factors and/or placental debris
play an important role in this disorder. The physiological actions of placental
debris occur via the balance between antiangiogenic and angiogenic factors.
Accordingly, this balance between antiangiogenic and angiogenic factors should be
investigated to elucidate the various pathological features of preeclampsia.
Their accurate evaluation is needed to investigate not only antiangiogenic
factors (such as sFlt-1 and sEng) and angiogenic factors (such as vascular
endothelial growth factor, placental growth factor and transforming growth factor
beta) but also the expression level of their receptors such as Flt-1 and Eng.
However, it is ethically and technically difficult to investigate the above
mentioned factors at antepartum in human patients. The examination of the ratios
of sFlt-1/vascular endothelial growth factor receptor ligands and
sEng/transforming vascular endothelial growth factor-beta and the use of
experimental animal models may help in elucidating various unresolved issues in
preeclampsia.
PMID- 25139040
TI - Gender-specific associations of appendicular muscle mass with BMD in elderly
Italian subjects.
AB - Currently used diagnostic measures for sarcopenia are based on the evaluation of
appendicular skeletal muscle mass (ASMM) divided by height-squared (ASMMI). This
study aimed to investigate the associations between different operational
definitions of appendicular muscle mass and BMD at different skeletal sites in
aging Italian men and women. In 1199 consecutive healthy Italian subjects, aged
55 years or more (854 women, age 64.2 +/- 6.4 years and 165 men, age 65.3 +/- 6.1
years), we measured BMD at the lumbar spine (LS-BMD), at femoral neck (FN-BMD),at
total hip (TH-BMD), at total body (WB-BMD) and at the right hand (H-BMD) and body
composition parameters [ASMM, ASMMI, ASMM/Weight, total lean mass and total fat
mass by DXA]. In all subjects, we also measured sex hormones, 25-hydroxyvitamin D
and bone turnover markers. In men, both ASMM and ASMMI were positively correlated
with BMD at all sites, whereas in women, ASMM and ASMMI did not show any
significant correlation with BMD. In men, multiple regression analyses showed
that ASMM was positively associated (p < 0.01) with FN-BMD, TH-BMD and H-BMD;
however, these associations were no longer present when lean mass was included.
In women, both fat mass and lean mass were found positively associated with BMD
at all sites. In conclusion, among the different operational measures of the
ASMM, only ASMM was significantly associated with BMD in elderly men, but not in
elderly women.
PMID- 25139043
TI - Dynamic NMR study of cyclic derivatives of pyridoxine.
AB - A series of pyridoxine derivatives was investigated by (1) H and 2D nuclear
overhauser enhancement spectroscopy (NOESY) NMR. The free energies of activation
for the pyridyl-oxygen rotation of the 2,4-dinitrophenyl ether of the seven
membered acetals of pyridoxine were measured by dynamic NMR. A conformational
exchange between the chair and twist forms of the seven-membered acetal ring was
confirmed by dynamic NMR and STO3G computations.
PMID- 25139042
TI - Burden of mental disorders and unmet needs among street homeless people in Addis
Ababa, Ethiopia.
AB - BACKGROUND: The impact of mental disorders among homeless people is likely to be
substantial in low income countries because of underdeveloped social welfare and
health systems. As a first step towards advocacy and provision of care, we
conducted a study to determine the burden of psychotic disorders and associated
unmet needs, as well as the prevalence of mental distress, suicidality, and
alcohol use disorder among homeless people in Addis Ababa, the capital of
Ethiopia. METHODS: A cross-sectional survey was conducted among street homeless
adults. Trained community nurses screened for potential psychosis and
administered standardized measures of mental distress, alcohol use disorder and
suicidality. Psychiatric nurses then carried out confirmatory diagnostic
interviews of psychosis and administered a locally adapted version of the
Camberwell Assessment of Needs Short Appraisal Schedule. RESULTS: We assessed 217
street homeless adults, about 90% of whom had experienced some form of mental or
alcohol use disorder: 41.0% had psychosis, 60.0% had hazardous or dependent
alcohol use, and 14.8% reported attempting suicide in the previous month.
Homeless people with psychosis had extensive unmet needs with 80% to 100%
reporting unmet needs across 26 domains. Nearly 30% had physical disability
(visual and sensory impairment and impaired mobility). Only 10.0% of those with
psychosis had ever received treatment for their illness. Most had lived on the
streets for over 2 years, and alcohol use disorder was positively associated with
chronicity of homelessness. CONCLUSION: Psychoses and other mental and
behavioural disorders affect most people who are street homeless in Addis Ababa.
Any programme to improve the condition of homeless people should include
treatment for mental and alcohol use disorders. The findings have significant
implications for advocacy and intervention programmes, particularly in similar
low income settings.
PMID- 25139044
TI - Biomimetic nanostructuring of copper thin films enhances adhesion to the negative
electrode laminate in lithium-ion batteries.
AB - Thin films of copper are widely used as current collectors for the negative
electrodes in lithium-ion batteries. However, a major cause of battery failure is
delamination between the current collector and the graphite anode. When silicon
or tin is used as active material, delamination becomes a key issue owing to the
large volume changes of these materials during lithation and delithation
processes. Learning from Nature, we developed a new biomimetic approach based on
the adhesion properties of the feet of geckos. The biomimetic approach improves
adhesion between the laminate and the copper surface by introducing an array of
Cu(OH)2 nanorods, which increases the surface area of the current collector. When
graphite anode laminate is casted onto regular and a modified copper surfaces,
the modified current collector displays superior adhesion to graphite and the
PVDF binder-based electrode. The electrochemical performance of the batteries
using these electrodes is not compromised by the additional chemistry of the
Cu(OH)2 on the copper surface. The technique can lead to enhanced battery
lifetimes over long-term cycling.
PMID- 25139045
TI - Cardiovascular disease risk is only elevated in hypertensive, formerly
preeclamptic women.
AB - OBJECTIVE: To analyse the predicted 10- and 30-year risk scores for
cardiovascular disease (CVD) in patients who experienced preeclampsia (PE) 5-10
years previously compared with healthy parous controls. DESIGN: Observational
study. SETTING: Tertiary referral hospital in the Netherlands. POPULATION: One
hundred and fifteen patients with a history of PE and 50 controls. PE patients
were categorised into two groups, hypertensive (n = 21) and normotensive (n =
94), based on use of antihypertensive medication, and next categorised into
subgroups based on the onset of PE: early-onset PE (n = 39) and late-onset PE (n
= 76). METHODS: All participants underwent cardiovascular risk screening 5-10
years after index pregnancy. We measured body mass, height and blood pressure.
Blood was analysed for fasting glucose, insulin and lipid levels. All
participants completed a validated questionnaire. The 10- and 30-year Framingham
risk scores were calculated and compared. MAIN OUTCOME MEASURES: Estimated
Framingham 10- and 30-year risk scores for CVD. RESULTS: The overall 10- and 30
year CVD median risks weighing subjects' lipids were comparable between formerly
PE women and controls; 1.6 versus 1.5% (P = 0.22) and 9.0 versus 9.0% (P = 0.49),
respectively. However, hypertensive formerly PE women have twice the CVD risk as
normotensive formerly PE women: 10- and 30-year CVD median risks were 3.1 versus
1.5% (P < 0.01) and 19.0% versus 8.0% (P < 0.01), respectively. Risk estimates
based on BMI rather than lipid profile show comparable results. Early-onset PE
clustered more often in the hypertensive formerly PE group and showed
significantly higher 10- and 30-year CVD risk estimates based on lipids compared
with the late-onset PE group: 1.7 versus 1.3% (P < 0.05) and 10.0 versus 7.0% (P
< 0.05), respectively. CONCLUSIONS: Women who are hypertensive after
preeclampsia, have a twofold risk of developing CVD in the next 10-30 years.
Formerly PE women who are normotensive in the first 10 years after their
preeclamptic pregnancy have a comparable future cardiovascular risk to healthy
controls.
PMID- 25139046
TI - Diabetic foot: lipids, new and old vascular risk markers.
PMID- 25139047
TI - Structure of the full-length insecticidal protein Cry1Ac reveals intriguing
details of toxin packaging into in vivo formed crystals.
AB - For almost half a century, the structure of the full-length Bacillus
thuringiensis (Bt) insecticidal protein Cry1Ac has eluded researchers, since Bt
derived crystals were first characterized in 1965. Having finally solved this
structure we report intriguing details of the lattice-based interactions between
the toxic core of the protein and the protoxin domains. The structure provides
concrete evidence for the function of the protoxin as an enhancer of native
crystal packing and stability.
PMID- 25139048
TI - Detection of insulin granule exocytosis by an electrophysiology method with high
temporal resolution reveals enlarged insulin granule pool in BIG3-knockout mice.
AB - We recently identified BIG3 as a negative regulator of insulin granule biogenesis
and reported increased insulin secretion in BIG3-knockout (BKO) mice. To pinpoint
the site of action for BIG3, we investigated whether BIG3 regulates quantal
insulin granule exocytosis. We established an assay to detect insulin granule
exocytosis by recording ATP-elicited currents at high temporal resolution by
patch clamp. Similarly to insulin, ATP release was increased in BKO beta-cells.
Although the frequency of insulin granule exocytosis was increased in BKO beta
cells, quantal size or release kinetics remained unchanged. Electron microscopy
studies showed that the number of insulin granules was increased by >60% in BKO
beta-cells. However, the number of morphologically docked granules was unaltered.
The number of insulin granules having significant distances away from plasma
membrane was greatly increased in BKO beta-cells. Thus, BIG3 negatively regulates
insulin granule exocytosis by restricting insulin granule biogenesis without the
release kinetics of individual granules at the final exocytotic steps being
affected. Depletion of BIG3 leads to an enlarged releasable pool of insulin
granules, which accounts for increased release frequency and consequently
increased insulin secretion.
PMID- 25139049
TI - Blood lipids affect rat islet blood flow regulation through beta3-adrenoceptors.
AB - Pancreatic islet blood perfusion varies according to the needs for insulin
secretion. We examined the effects of blood lipids on pancreatic islet blood flow
in anesthetized rats. Acute administration of Intralipid to anesthetized rats
increased both triglycerides and free fatty acids, associated with a simultaneous
increase in total pancreatic and islet blood flow. A preceding abdominal vagotomy
markedly potentiated this and led acutely to a 10-fold increase in islet blood
flow associated with a similar increase in serum insulin concentrations. The
islet blood flow and serum insulin response could be largely prevented by
pretreatment with propranolol and the selective beta3-adrenergic inhibitor SR
59230A. The nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester
prevented the blood flow increase but was less effective in reducing serum
insulin. Increased islet blood flow after Intralipid administration was also seen
in islet and whole pancreas transplanted rats, i.e., models with different
degrees of chronic islet denervation, but the effect was not as pronounced. In
isolated vascularly perfused single islets Intralipid dilated islet arterioles,
but this was not affected by SR-59230A. Both the sympathetic and parasympathetic
nervous system are important for the coordination of islet blood flow and insulin
release during hyperlipidemia, with a previously unknown role for beta3
adrenoceptors.
PMID- 25139052
TI - Vitamin D, asthma prevalence and asthma exacerbations: a large adult population
based study.
AB - BACKGROUND: The impact of low vitamin D status on asthma, asthma morbidity and
control is unclear. We aimed to investigate in adults the associations between
serum 25-hydroxyvitamin D level and prevalent asthma as well as asthma
exacerbations. METHODS: A cohort of Israeli adults aged 22-50 years with
documented vitamin D status were extracted from Clalit Health Services (HMO)
between July 1, 2008 and July 1, 2012. Among this population, those with
physician-diagnosed asthma and asthma exacerbations were identified. Asthma
exacerbations were defined as any of the following: prescription for oral
corticosteroids, >5 prescriptions for short acting beta agonists and more than
four visits to a physician for asthma. Logistic regression models assessed the
associations between vitamin D and both asthma and asthma exacerbations. RESULTS:
Approximately 308 000 members with at least one vitamin D measurement were
included in the cohort. Among them, 6.9% (21 237) had physician-diagnosed asthma
vs 5.7% in the general population. Serum 25-OHD levels across both groups were
similar. However, among those with vitamin D deficiency, the odds of having an
exacerbation were 25% greater compared to those with levels in the normal range.
This association remained significant after controlling for known confounders.
CONCLUSION: While there was no significant association between vitamin D status
and physician-diagnosed asthma, there was a strong association with asthma
exacerbations. The presented evidence supports vitamin D screening in the
subgroup of asthmatics that are uncontrolled and experience recurrent
exacerbations.
PMID- 25139051
TI - SUMOylation protects against IL-1beta-induced apoptosis in INS-1 832/13 cells and
human islets.
AB - Posttranslational modification by the small ubiquitin-like modifier (SUMO)
peptides, known as SUMOylation, is reversed by the sentrin/SUMO-specific
proteases (SENPs). While increased SUMOylation reduces beta-cell exocytosis,
insulin secretion, and responsiveness to GLP-1, the impact of SUMOylation on
islet cell survival is unknown. Mouse islets, INS-1 832/13 cells, or human islets
were transduced with adenoviruses to increase either SENP1 or SUMO1 or were
transfected with siRNA duplexes to knockdown SENP1. We examined insulin
secretion, intracellular Ca2+ responses, induction of endoplasmic reticulum
stress markers and inducible nitric oxide synthase (iNOS) expression, and
apoptosis by TUNEL and caspase 3 cleavage. Surprisingly, upregulation of SENP1
reduces insulin secretion and impairs intracellular Ca2+ handling. This secretory
dysfunction is due to SENP1-induced cell death. Indeed, the detrimental effect of
SENP1 on secretory function is diminished when two mediators of beta-cell death,
iNOS and NF-kappaB, are pharmacologically inhibited. Conversely, enhanced
SUMOylation protects against IL-1beta-induced cell death. This is associated with
reduced iNOS expression, cleavage of caspase 3, and nuclear translocation of NF
kappaB. Taken together, these findings identify SUMO1 as a novel antiapoptotic
protein in islets and demonstrate that reduced viability accounts for impaired
islet function following SENP1 up-regulation.
PMID- 25139053
TI - Karyotype evolution in the horseshoe bat Rhinolophus sedulus by whole-arm
reciprocal translocation (WART).
AB - Robertsonian (centric) fusion or fission is one of the predominant modes of
chromosomal rearrangement in karyotype evolution among mammals. However, in
karyotypes composed of only bi-armed chromosomes, creation of new chromosomal arm
combinations in one step is possible only via whole-arm reciprocal translocation
(WART). Although this type of rearrangement has often been proposed to play an
important role in chromosomal evolution, direct observations of WARTs remained
rare, and, in most cases, were found in hybrids of chromosomal races in the
genera Mus and Sorex. For the first time, we present the karyotype of the
horseshoe bat species Rhinolophus sedulus (2n = 28, FNa = 52), where a WART
between 2 metacentric autosomes was detected by G-banding and confirmed by FISH
with painting probes of the vespertilionid bat Myotis myotis. Among the 6
specimens analyzed, 2 showed the heterozygous condition of the WART, 1 showed the
presumed ancestral, and 3 specimens showed the derived homozygous state. As the
existence of a hybrid zone at the sampling locality is thought to be rather
improbable, the WART may indicate ongoing karyotype evolution in this taxon.
PMID- 25139050
TI - Loss of vitamin D receptor signaling from the mammary epithelium or adipose
tissue alters pubertal glandular development.
AB - Vitamin D3 receptor (VDR) signaling within the mammary gland regulates various
postnatal stages of glandular development, including puberty, pregnancy,
involution, and tumorigenesis. Previous studies have shown that vitamin D3
treatment induces cell-autonomous growth inhibition and differentiation of
mammary epithelial cells in culture. Furthermore, mammary adipose tissue serves
as a depot for vitamin D3 storage, and both epithelial cells and adipocytes are
capable of bioactivating vitamin D3. Despite the pervasiveness of VDR in mammary
tissue, individual contributions of epithelial cells and adipocytes, as well as
the VDR-regulated cross-talk between these two cell types during pubertal mammary
development, have yet to be investigated. To assess the cell-type specific effect
of VDR signaling during pubertal mammary development, novel mouse models with
mammary epithelial- or adipocyte-specific loss of VDR were generated.
Interestingly, loss of VDR in either cellular compartment accelerated ductal
morphogenesis with increased epithelial cell proliferation and decreased
apoptosis within terminal end buds. Conversely, VDR signaling specifically in the
mammary epithelium modulated hormone-induced alveolar growth, as ablation of VDR
in this cell type resulted in precocious alveolar development. In examining
cellular cross-talk ex vivo, we show that ligand-dependent VDR signaling in
adipocytes significantly inhibits mammary epithelial cell growth in part through
the vitamin D3-dependent production of the cytokine IL-6. Collectively, these
studies delineate independent roles for vitamin D3-dependent VDR signaling in
mammary adipocytes and epithelial cells in controlling pubertal mammary gland
development.
PMID- 25139054
TI - Pulmonary metastasis of giant cell tumor of bones.
AB - Giant cell tumor of bone (GCTB) accounts for 5% of primary skeletal tumors.
Although it is considered to be a benign lesion, there are still incidences of
pulmonary metastasis. Pulmonary metastasis of GCTB may be affected by tumor
grading and localization as well as the age, gender and overall health status of
the patient. Patients with local recurrence are more likely to develop pulmonary
metastasis of GCTB. High expression of some genes, cytokines and chemokines may
also be closely related to the metastatic potential and prognosis of GCTB. The
treatment of the primary GCTB is key to the final outcome of the disease, as
intralesional curettage has a significantly higher local recurrence and pulmonary
metastasis rate than wide resection. However, even patients with pulmonary
metastasis seem to have a good prognosis after timely and appropriate surgical
resection. It is hoped that with the development of novel surgical methods and
drugs, pulmonary metastasis of GCTB can be prevented and treated more
effectively.
PMID- 25139055
TI - Effect of natural compounds on insulin signaling.
AB - Results of several epidemiological studies have indicated that diabetes mellitus
will become a global epidemic in the next decades, being more than 400 million
the human subjects in the world affected by this disease in the 2030. Most of
these subjects will be affected by type 2 diabetes mellitus (T2DM) whose
diffusion is mainly related to excessive caloric upload, sedentary life and
obesity. Typically, the treatment for T2DM is diet, weight control, physical
activity or hypoglycaemic and/or lipid-lowering drugs. Unfortunately, these drugs
often show low effectiveness or adverse side effects, thereby forcing patient to
discontinue medical treatment. Nevertheless traditional medicine suggests the use
of several formulations or medicinal foods to treat T2DM. Most of them are
characterized by safety, low cost, effectiveness, and good availability. Before
the advent of modern pharmacology, these remedies were used to treat diabetes and
obesity or prevent their onset. Today, we know that their effectiveness is due to
the presence of several bioactive compounds able to influence insulin signaling
pathway and cellular metabolism. In the last decades, many efforts have been
carried out to clarify their action mechanism. Here we provide a classification
of the natural compounds that stimulate the insulin pathway, highlighting their
effectiveness in controlling glycaemia on diabetic animal models or improving
insulin signaling in cellular systems.
PMID- 25139056
TI - Adjunctive graded body image exposure for eating disorders: A randomized
controlled initial trial in clinical practice.
AB - OBJECTIVE: Graded body image exposure is a key component of CBT for eating
disorders (EDs). However, despite being a highly anxiety-provoking intervention,
its specific effectiveness is unknown. The aims of this initial study were to
investigate the feasibility and preliminary effectiveness of individualized
graded body image exposure to a range of feared/avoided body image-related
situations in a sample of partially remitted ED patients. METHOD: Forty-five
female adult participants were randomly assigned to maintenance treatment as
usual (MTAU) only or MTAU plus five sessions of graded body image exposure.
RESULTS: The graded body image exposure intervention led to large improvements in
body avoidance as measured by two different methods. In addition, there was
evidence of a significant impact of body image exposure on the overvaluation of
shape, but not weight, 5 months after treatment. DISCUSSION: Taken together, the
current results provide evidence of the feasibility of adjunctive individualized
graded body image exposure within a clinical treatment program and suggest that
graded body image exposure reduces body avoidance behaviors in partially remitted
ED patients. Our findings suggest that individualized graded body image exposure
shows promise as an intervention targeting the overvaluation of shape in EDs.
PMID- 25139058
TI - Impact of optical antennas on active optoelectronic devices.
AB - Remarkable progress has been made in the fabrication and characterization of
optical antennas that are integrated with optoelectronic devices. Herein, we
describe the fundamental reasons for and experimental evidence of the dramatic
improvements that can be achieved by enhancing the light-matter interaction via
an optical antenna in both photon-emitting and -detecting devices. In addition,
integration of optical antennas with optoelectronic devices can lead to the
realization of highly compact multifunctional platforms for future integrated
photonics, such as low-cost lab-on-chip systems. In this review paper, we further
focus on the effect of optical antennas on the detectivity of infrared
photodetectors. One particular finding is that the antenna can have a dual effect
on the specific detectivity, while it can elevate light absorption efficiency of
sub-wavelength detectors, it can potentially increase the noise of the detectors
due to the enhanced spontaneous emission rate. In particular, we predict that the
detectivity of interband photon detectors can be negatively affected by the
presence of optical antennas across a wide wavelength region covering visible to
long wavelength infrared bands. In contrast, the detectivity of intersubband
detectors could be generally improved with a properly designed optical antenna.
PMID- 25139059
TI - A review of the provision of appropriate advice by pharmacy staff for self
medication in developing countries.
AB - BACKGROUND: Patients in developing countries often prefer to self-medicate via
community pharmacies. Pharmacy staff are therefore in a strategic position to
optimize the health of the public by providing appropriate advice to patients who
self-medicate. OBJECTIVE: To determine the proportion of pharmacy staff who
provide appropriate advice when handling self-medication requests in developing
countries. METHOD: A literature search was undertaken via MEDLINE, EMBASE, CINAHL
Plus, Web of Science and International Pharmaceutical Abstracts. Studies that
reported on the proportion of pharmacy staff providing appropriate advice when
handling self-medication requests in developing countries were included. The
appropriateness of advice was determined by each author's definition in the
original studies. RESULTS: Twenty-eight studies met the inclusion criteria. There
were variations in methods, scenarios, how the authors reported and defined
appropriate advice, and study populations. The proportion of pharmacy staff
providing appropriate advice varied widely from 0% to 96%, with a minority
providing appropriate advice in 83% of the scenarios performed. CONCLUSION: There
was considerable variation in results, with the majority of studies reporting
that inappropriate advice was provided by pharmacy staff when handling self
medication requests in developing countries. Consistent and robust methods are
required to provide comparisons across practice settings. There is also a need to
identify contributing factors to poor provision of advice for developing
intervention strategies for practice improvement.
PMID- 25139060
TI - The costs of hepatitis A infections in South Korea.
AB - OBJECTIVES: The incidence of hepatitis A infections among young adults has
recently increased in South Korea. Although universal vaccination has often been
suggested to mitigate the problem, its rationale has not been well-understood.
Estimating the societal costs of hepatitis A infections might support the
development of intervention strategies. METHODS: We classified hepatitis A
infections into eight clinical pathways and estimated the number of occurrences
and cost per case for each clinical pathway using claim data from National Health
Insurance and several national surveys as well as assumptions based on previous
studies. To determine the total costs of a hepatitis A infection, both direct and
indirect costs were estimated. Indirect costs were estimated using the human
capital approach. All costs are adjusted to the year 2008. RESULTS: There were
30,240 identified cases of hepatitis A infections in 2008 for a total cost of
80,873 million won (2.7 million won per case). Direct and indirect costs
constituted 56.2% and 43.8% of the total costs, respectively. People aged 20-39
accounted for 71.3% of total cases and 74.6% of total costs. Medical costs per
capita were the lowest in the 0-4 age group and highest in the 20-29 age group.
CONCLUSIONS: This study could provide evidence for development of cost-effective
interventions to control hepatitis A infections. But the true costs including
uncaptured and intangible costs of hepatitis A infections might be higher than
our results indicate.
PMID- 25139057
TI - A multilevel understanding of HIV/AIDS disease burden among African American
women.
AB - Disproportionate HIV/AIDS rates among African American women have been examined
extensively, primarily from an individual-centered focus. Beyond individual
behaviors, factors such as the hyperincarceration of African American men and
geographically concentrated disadvantage may better explain inequitable disease
burden. In this article I propose a conceptual model of individual, social, and
structural factors that influence HIV transmission among African American women.
The model can be used to develop comprehensive assessments and guide prevention
programs in African American communities.
PMID- 25139061
TI - Improvement to the scanning electron microscope image adaptive Canny optimization
colorization by pseudo-mapping.
AB - An improvement to the previously proposed adaptive Canny optimization technique
for scanning electron microscope image colorization is reported. The additional
feature, called pseudo-mapping technique, is that the grayscale markings are
temporarily mapped to a set of pre-defined pseudo-color map as a mean to instill
color information for grayscale colors in chrominance channels. This allows the
presence of grayscale markings to be identified; hence optimization colorization
of grayscale colors is made possible. This additional feature enhances the
flexibility of scanning electron microscope image colorization by providing wider
range of possible color enhancement. Furthermore, the nature of this technique
also allows users to adjust the luminance intensities of selected region from the
original image within certain extent.
PMID- 25139062
TI - Homeostatic sleep pressure is the primary factor for activation of cortical
nNOS/NK1 neurons.
AB - Cortical interneurons, immunoreactive for neuronal nitric oxide synthase (nNOS)
and the receptor NK1, express the functional activity marker Fos selectively
during sleep. NREM sleep 'pressure' is hypothesized to accumulate during waking
and to dissipate during sleep. We reported previously that the proportion of
Fos(+) cortical nNOS/NK1 neurons is correlated with established
electrophysiological markers of sleep pressure. As these markers covary with the
amount of NREM sleep, it remained unclear whether cortical nNOS/NK1 neurons are
activated to the same degree throughout NREM sleep or whether the extent of their
activation is related to the sleep pressure that accrued during the prior waking
period. To distinguish between these possibilities, we used hypnotic medications
to control the amount of NREM sleep in rats while we varied prior wake duration
and the resultant sleep pressure. Drug administration was preceded by 6 h of
sleep deprivation (SD) ('high sleep pressure') or undisturbed conditions ('low
sleep pressure'). We find that the proportion of Fos(+) cortical nNOS/NK1 neurons
was minimal when sleep pressure was low, irrespective of the amount of time spent
in NREM sleep. In contrast, a large proportion of cortical nNOS/NK1 neurons was
Fos(+) when an equivalent amount of sleep was preceded by SD. We conclude that,
although sleep is necessary for cortical nNOS/NK1 neuron activation, the
proportion of cells activated is dependent upon prior wake duration.
PMID- 25139063
TI - Dynamic interactions between plasma IL-1 family cytokines and central endogenous
opioid neurotransmitter function in humans.
AB - Evidence in animal models suggests IL-1 family cytokines interact with central
endogenous opioid neurotransmitter systems, inducing or perpetuating pathological
states such as persistent pain syndromes, depression, substance use disorders,
and their comorbidity. Understanding these interactions in humans is particularly
relevant to understanding pathological states wherein this neurotransmitter
system is implicated (ie, persistent pain, mood disorders, substance use
disorders, etc). Here, we examined relationships between IL-1beta, IL-1ra, and
functional measures of the endogenous opioid system in 34 healthy volunteers, in
the absence and presence of a standardized sustained muscular pain challenge, a
psychophysical challenge with emotionally and physically stressful components. Mu
opioid receptor availability in vivo was examined with [(11)C]carfentanil
positron emission tomography (PET) scanning. Sex and neuroticism impacted IL-1
family cytokines; higher baseline IL-1beta and IL-1ra was identified in females
with lower neuroticism. Higher baseline IL-1beta was also associated with reduced
MU-opioid receptor availability (amygdala) and greater pain sensitivity. The pain
challenge increased IL-1beta in females with high neuroticism. Strong
associations between IL-1ra (an anti-nociceptive cytokine) and MU-opioid receptor
activation (VP/NAcc) were identified during the pain challenge and the resulting
analgesic effect of MU-opioid receptor activation was moderated by changes in IL
1beta whereby volunteers with greater pain induced increase in IL-1beta
experienced less endogenous opioid analgesia. This study demonstrates the
presence of relationships between inflammatory factors and a specific central
neurotransmitter system and circuitry, of relevance to understanding
interindividual variations in regulation of responses to pain and other physical
and emotional stressors.
PMID- 25139064
TI - Functional genetic variation of the cannabinoid receptor 1 and cannabis use
interact on prefrontal connectivity and related working memory behavior.
AB - Cannabinoid signaling is involved in different brain functions and it is mediated
by the cannabinoid receptor 1 (CNR1), which is encoded by the CNR1 gene. Previous
evidence suggests an association between cognition and cannabis use. The logical
interaction between genetically determined cannabinoid signaling and cannabis use
has not been determined. Therefore, we investigated whether CNR1 variation
predicts CNR1 prefrontal mRNA expression in postmortem prefrontal human tissue.
Then, we studied whether functional variation in CNR1 and cannabis exposure
interact in modulating prefrontal function and related behavior during working
memory processing. Thus, 208 healthy subjects (113 males) were genotyped for the
relevant functional SNP and were evaluated for cannabis use by the Cannabis
Experience Questionnaire. All individuals performed the 2-back working memory
task during functional magnetic resonance imaging. CNR1 rs1406977 was associated
with prefrontal mRNA and individuals carrying a G allele had reduced CNR1
prefrontal mRNA levels compared with AA subjects. Moreover, functional
connectivity MRI demonstrated that G carriers who were also cannabis users had
greater functional connectivity in the left ventrolateral prefrontal cortex and
reduced working memory behavioral accuracy during the 2-back task compared with
the other groups. Overall, our results indicate that the deleterious effects of
cannabis use are more evident on a specific genetic background related to its
receptor expression.
PMID- 25139065
TI - Hypoactivation of the ventral and dorsal striatum during reward and loss
anticipation in antipsychotic and mood stabilizer-naive bipolar disorder.
AB - Increased activity within known reward-processing neurocircuitry (eg, ventral
striatum, VS) has been reported among medicated individuals with bipolar disorder
(BD) I and II. However, such findings are confounded by the potential
ameliorative effects of mood-stabilizing and antipsychotic medications on neural
activations. This study tests the hypothesis that a pathophysiological locus of
alterations in reward processing is present within the striatum in antipsychotic
and lithium-naive individuals with BD. Twenty antipsychotic and lithium-naive
individuals with BD II or BD not-otherwise specified (NOS) and 20 matched healthy
comparison individuals participated in functional magnetic resonance imaging
during the performance of a monetary incentive delay task. Between-group
comparisons were conducted using small-volume correction focusing on orthogonal a
priori regions of interest centered in the VS and dorsal striatum (DS),
respectively. During reward anticipation, unmedicated individuals with BD II/NOS
had decreased activity within the DS (but not VS). During loss anticipation, on
the other hand, decreased activation within both the VS and DS was observed.
Across all participants, DS activity (during reward anticipation) was positively
associated with putamen volume. This is the first report of decreased dorsal and
ventral striatal activity among unmedicated individuals with BD II/NOS. These
data contradict a simple 'reward hypersensitivity' model of BD, and add to a
growing body of literature suggesting that blunted reward processing may be a
vulnerability factor for both mood- and addiction-related disorders.
PMID- 25139066
TI - Chemoenzymatic synthesis of trehalose analogues: rapid access to chemical probes
for investigating mycobacteria.
AB - Trehalose analogues are emerging as valuable tools for investigating
Mycobacterium tuberculosis, but progress in this area is slow due to the
difficulty in synthesizing these compounds. Here, we report a chemoenzymatic
synthesis of trehalose analogues that employs the heat-stable enzyme trehalose
synthase (TreT) from the hyperthermophile Thermoproteus tenax. By using TreT,
various trehalose analogues were prepared quickly (1 h) in high yield (up to >99
% by HPLC) in a single step from readily available glucose analogues. To
demonstrate the utility of this method in mycobacteria research, we performed a
simple "one-pot metabolic labeling" experiment that accomplished probe synthesis,
metabolic labeling, and imaging of M. smegmatis in a single day with only TreT
and commercially available materials.
PMID- 25139067
TI - Liver resection for colorectal metastases: results and prognostic factors with 10
year follow-up.
AB - PURPOSE: Actual 5-year survival rates after resection of colorectal liver
metastases (CLM) are 25-45%, whereas 10-year survival rates are extrapolated from
survival curves. Few studies have reported long-term survivors with 10 years of
actual follow-up. Therefore, no recurrences occurring after 10-plus years have
been reported. The aim of our study was to analyze actual 10-year survival rates
and prognostic factors. METHODS: Clinical data of patients with CLM who had
undergone first liver resection in our center between January 1990 and December
2000 were retrospectively analyzed. RESULTS: Eighty-nine patients of mean age 64
years were studied. Three patients were excluded from the study: one because of
postoperative death, and two from being lost to follow-up. All other subjects had
a potential 10-year follow-up. Only 33% patients received perioperative
chemotherapy. The actual 10-year overall and disease-free survival rate were 22
and 19%, respectively. Poor prognostic factors were disease-free interval less
than 1 year, wedge liver resection, clinical risk score>2, segment 1 CLM
location, and peritumoral lymphangitis. Good prognostic factors were tumors
having mucinous components in primary tumor and CLM located in the right lobe.
CONCLUSIONS: With actual long-term follow-up for 10 years, disease-free survival
rate is 19% and mainly depends on surgical management. Recurrence continues to
occur more than 5 years after liver resection for CLM; cure cannot be assumed at
this time. Clinical risk score is a good predictor of cure and should be taken
into account when choosing perioperative treatment.
PMID- 25139068
TI - Development of a dynamic model for ventral hernia mesh repair.
AB - INTRODUCTION: The adequate way of mesh fixation in laparoscopic ventral hernia
repair is still subject to debate. So far, simulation has only been carried out
in a static way, thereby omitting dynamic effects of coughing or vomiting. We
developed a dynamic model of the anterior abdominal wall. MATERIALS AND METHODS:
An aluminium cylinder was equipped with a pressure controlled, fluid-filled
plastic bag, simulating the abdominal viscera. A computer-controlled system
allowed the control of influx and efflux, thus creating pressure peaks of up to
200 mmHg to simulate coughing and 290 mmHg to simulate vomiting. We tested
fixation with tacks (Absorbatack, Covidien Deutschland, Neustadt a. D., Germany).
The model was controlled for the friction coefficient of the tissue against the
mesh and the physiologic elasticity of the abdominal wall surrogate. RESULTS: The
model was able to create pressure peaks equivalent to physiologic coughs or
vomiting. Physiologic elasticity was thereby maintained. We could show that the
friction coefficient is crucial to achieve a physiologic situation. The meshes
showed a tendency to dislocate with an increasing number of coughs (Fig. 4).
Nevertheless, when applied in a plain manner, the meshes withstood more cough
cycles than when applied with a bulge as in laparoscopic surgery. CONCLUSIONS:
The dynamic movement of the abdominal wall, the friction between tissue and mesh
and the way of mesh application are crucial factors that have to be controlled
for in simulation of ventral abdominal hernia closure. We could demonstrate that
patient specific factors such as the frequency of coughing as well as the
application technique influence the long term stability of the mesh.
PMID- 25139069
TI - The Charlson comorbidity index predicts survival after disease recurrence in
patients following radical cystectomy for urothelial carcinoma of the bladder.
AB - OBJECTIVE: To identify prognostic clinical and histopathological parameters,
including comorbidity indices at the time of radical cystectomy (RC), for overall
survival (OS) after recurrence following RC for urothelial carcinoma of the
bladder (UCB). MATERIALS AND METHODS: A retrospective multicenter study was
carried out in 555 unselected consecutive patients who underwent RC with pelvic
lymph node dissection for UCB from 2000 to 2010. A total of 227 patients with
recurrence comprised our study group. Cox proportional hazards regression models
were calculated with established variables to assess their independent influence
on OS after recurrence. RESULTS: The median time from RC to recurrence and the
median OS after recurrence was 10.9 and 5.4 months, respectively. Neither the
time to recurrence nor the type of recurrence (systematic vs. local) was
predictive of the OS. In contrast, age (hazard ratio (HR) 1.53, p = 0.011), lymph
node metastasis (HR 1.56, p = 0.007), and positive surgical margins (HR 1.53, p =
0.046) significantly affected the OS after disease recurrence. In addition, the
dichotomized Charlson comorbidity index (CCI; dichotomized into >2 vs. 0-2) was
the only comorbidity score with an independent prediction of OS (HR 1.41, p =
0.033). We observed a significant gain in the base model's predictive accuracy,
i.e. from 68.4 to 70.3% (p < 0.001), after inclusion of the dichotomized CCI.
CONCLUSIONS: We present the first outcome study of comorbidity indices used as
predictors of OS after disease recurrence in patients undergoing RC for UCB. The
CCI at the time of RC had no significant influence on the time to recurrence but
represented an independent predictor of OS after disease recurrence.
PMID- 25139070
TI - Assessment of mass transfer and mixing in rigid lab-scale disposable bioreactors
at low power input levels.
AB - Mass transfer, mixing times and power consumption were measured in rigid
disposable stirred tank bioreactors and compared to those of a traditional glass
bioreactor. The volumetric mass transfer coefficient and mixing times are usually
determined at high agitation speeds in combination with sparged aeration as used
for single cell suspension and most bacterial cultures. In contrast, here low
agitation speeds combined with headspace aeration were applied. These settings
are generally used for cultivation of mammalian cells growing adherent to
microcarriers. The rigid disposable vessels showed similar engineering
characteristics compared to a traditional glass bioreactor. On the basis of the
presented results appropriate settings for adherent cell culture, normally
operated at a maximum power input level of 5 W m(-3) , can be selected. Depending
on the disposable bioreactor used, a stirrer speed ranging from 38 to 147 rpm
will result in such a power input of 5 W m(-3) . This power input will mix the
fluid to a degree of 95% in 22 +/- 1 s and produce a volumetric mass transfer
coefficient of 0.46 +/- 0.07 h(-1) .
PMID- 25139071
TI - Surface plasmon enhanced photochemical etching of p-type GaP: a direct
demonstration of wavelength selectivity.
AB - We report here on significant enhancement of the photochemical etching of p-type
gallium phosphide (GaP) by Au plasmonic nanostructures. The photochemical etching
rate of defect (dislocation) states of Au-coated p-GaP samples is ten times
higher than blank samples when irradiated with 532 nm laser. It is confirmed that
the enhancement of photochemical etching is wavelength selective. Only 532 nm
laser can efficiently increase the photochemical etching rate, while lasers of
other wavelengths (375, 405, 445, and 473 nm) show limited or negative effects.
This observation can be attributed to defect (dislocation) enhanced photochemical
etching through localized surface plasmon resonance of Au nanostructures. This
method may open a new pathway for controlled fabrication of novel optoelectronic
devices.
PMID- 25139073
TI - Injectional anthrax - new presentation of an old disease.
AB - Bacillus anthracis infection (anthrax) has three distinct clinical presentations
depending on the route of exposure: cutaneous, gastrointestinal and inhalational
anthrax. Each of these can lead to secondary bacteraemia and anthrax meningitis.
Since 2009,anthrax has emerged among heroin users in Europe,presenting a novel
clinical manifestation, 'injectional anthrax', which has been attributed to
contaminated heroin distributed throughout Europe; before 2009 only one case was
reported. During 2012 and 2013,new cases of injectional anthrax were diagnosed in
Denmark, France, Germany, and the United Kingdom.Here we present a comprehensive
review of the literature and information derived from different reporting systems
until 31 December 2013. Overall 70 confirmed cases were reported, with 26
fatalities (37% case fatality rate).The latest two confirmed cases occurred in
March 2013. Thirteen case reports have been published,describing 18 confirmed
cases. Sixteen of these presented as a severe soft tissue infection that differed
clinically from cutaneous anthrax, lacked the characteristic epidemiological
history of animal contact and ten cases required complimentary surgical
debridement. These unfamiliar characteristics have led to delays of three to 12
days in diagnosis, inadequate treatment and a high fatality rate. Clinicians'
awareness of this recently described clinical entity is key for early 'and
successful management of patients.
PMID- 25139072
TI - Psychometric Properties of Two Brief Versions of the Voices Acceptance and Action
Scale (VAAS): Implications for the Second-wave and Third-wave Behavioural and
Cognitive Approaches to Auditory Hallucinations.
AB - Despite a steep rise in the evidence base for third-wave cognitive and
behavioural therapy approaches over the past decade, a scarcity of change
measures relevant to these therapies as applied to psychosis is arguably slowing
empirical progress in the area. The Voices Acceptance and Action Scale (VAAS), a
measure of acceptance of voice experiences, is a notable exception. However,
there are no published data on its psychometric properties outside of that
provided by the scale developers. The current study explored the psychometric
properties of two brief versions of the VAAS in a sample of psychotic voice
hearers in a routine outpatient mental health service. Evidence from the current
study suggests that both brief versions are robust measures of acceptance of
voice experiences. Some limited support for the shortened VAAS-9 as being a
marginally improved scale over the original brief VAAS-12 was also found. The
current study found acceptance of voices to be highly related to depression,
anxiety, stress and general negative affect and to predict unique variance in
depression and general negative affect beyond that attributable to negative
beliefs about voices and thought suppression. It was also found that acceptance
was positively related to the use of reappraisal, indicating that the
distinctiveness of acceptance from appraisal processes may be less pronounced in
this context than what was has been reported previously. Implications for future
research, as well as the practice of second-wave and third-wave cognitive and
behavioural approaches to psychosis, are discussed. KEY PRACTITIONER MESSAGE: Two
brief versions of the VAAS instrument were found to be robust measures of
acceptance of psychotic voice experiences. The construct of acceptance of voices
is highly related to indices of well-being and negative appraisal processes in
psychosis and appears to offer an alternative route to therapeutically addressing
the toxic effects of negative beliefs about voices. The recent focus on
acceptance-based techniques within cognitive and behavioural approaches to
psychosis was supported.
PMID- 25139074
TI - Increase of pertussis incidence in 2010 to 2012 after 12 years of low circulation
in Spain.
AB - In Spain, whole cell pertussis vaccination started in 1975, with three doses
before the age of 6-7 months. Doses at 15-18 months and 4-6 years were introduced
in 1996 and 2001, respectively. Spain switched to an acellular vaccine in 2005.
From 1998 to 2009, pertussis incidence rates remained <=1.5 cases/100,000
inhabitants but increased from 2010 to 7.5 cases/100,000 in 2012. Data from 1998
to 2012 were analysed to assess disease trends and susceptible populations. We
defined four epidemic periods: 1998-2001 (reference), 2002-05, 2006-09 and 2010
12. In 2002-05, the incidence rate increased in individuals aged 15-49 years
(IRR: 1.41 (95% CI: 1.11-1.78)) and >=50 years (IRR: 2.78 (95% CI: 1.78-4.33))
and in 2006-09 increased also in infants aged <3 months (IRR: 1.83 (95% CI: 1.60
2.09)). In 2010-12, the incidence rate increased notably in all age groups, with
IRRs ranging between 2.5 (95% CI: 2.3-2.8) in 5-9 year-olds and 36.0 (95% CI:
19.4-66.8) in 20-29 year-olds. These results, consistent with the country's
vaccination history, suggest a progressive accumulation of susceptible
individuals due to waning immunity after years of low incidence. Further
vaccination strategies should be assessed and implemented to prevent pertussis in
pre-vaccinated infants, in whom the disease is more severe.
PMID- 25139075
TI - Potential association between the recent increase in campylobacteriosis incidence
in the Netherlands and proton-pump inhibitor use - an ecological study.
AB - The Netherlands saw an unexplained increase in campylobacteriosis incidence
between 2003 and 2011, following a period of continuous decrease. We conducted an
ecological study and found a statistical association between campylobacteriosis
incidence and the annual number of prescriptions for proton pump inhibitors
(PPIs), controlling for the patient's age, fresh and frozen chicken purchases
(with or without correction for campylobacter prevalence in fresh poultry meat).
The effect of PPIs was larger in the young than in the elderly. However, the
counterfactual population-attributable fraction for PPIs was largest for the
elderly (ca 45% in 2011) and increased at population level from 8% in 2004 to 27%
in 2011. Using the regression model and updated covariate values, we predicted a
trend break for 2012, largely due to a decreased number of PPI prescriptions,
that was subsequently confirmed by surveillance data. Although causality was not
shown, the biological mechanism, age effect and trend-break prediction suggest a
substantial impact of PPI use on campylobacteriosis incidence in the Netherlands.
We chose the ecological study design to pilot whether it is worthwhile to further
pursue the effect of PPI on campylobacteriosis and other gastrointestinal
pathogens in prospective cohort studies. We now provide strong arguments to do
so.
PMID- 25139076
TI - The hanta hunting study: underdiagnosis of Puumala hantavirus infections in
symptomatic non-travelling leptospirosis-suspected patients in the Netherlands,
in 2010 and April to November 2011.
AB - Leptospirosis and haemorrhagic fever with renal syndrome (HFRS) are hard to
distinguish clinically since these two important rodent-borne zoonoses share
hallmark symptoms such as renal failure and haemorrhage. Leptospirosis is caused
by infection with a spirochete while HFRS is the result of an infection with
certain hantaviruses. Both diseases are relatively rare in the Netherlands.
Increased incidence of HFRS has been observed since 2007 in countries that border
the Netherlands. Since a similar rise in incidence has not been registered in the
Netherlands, we hypothesise that due to overlapping clinical manifestations,
hantavirus infections may be confused with leptospirosis, leading to
underdiagnosis. Therefore, we tested a cohort of non-travelling Dutch patients
with symptoms compatible with leptospirosis, but with a negative diagnosis,
during 2010 and from April to November 2011. Sera were screened with pan
hantavirus IgG and IgM enzyme-linked immunosorbent assays (ELISAs). Sera with IgM
reactivity were tested by immunofluorescence assay (IFA). ELISA (IgM positive)
and IFA results were confirmed using focus reduction neutralisation tests
(FRNTs). We found hantavirus-specific IgG and/or IgM antibodies in 4.3% (11/255)
of samples taken in 2010 and in 4.1% (6/146) of the samples during the 2011
period. After FRNT confirmation, seven patients were classed as having acute
Puumala virus infections. A review of hantavirus diagnostic requests revealed
that at least three of the seven confirmed acute cases as well as seven probable
acute cases of hantavirus infection were missed in the Netherlands during the
study period.
PMID- 25139077
TI - WHO publishes handbook on the analysis of TB surveillance data.
PMID- 25139080
TI - CRPS-related neurogenic edema responsive to dextromethorphan/quinidine.
PMID- 25139079
TI - Phosphonated near-infrared fluorophores for biomedical imaging of bone.
AB - The conventional method for creating targeted contrast agents is to conjugate
separate targeting and fluorophore domains. A new strategy is based on the
incorporation of targeting moieties into the non-delocalized structure of
pentamethine and heptamethine indocyanines. Using the known affinity of
phosphonates for bone minerals in a model system, two families of bifunctional
molecules that target bone without requiring a traditional bisphosphonate are
synthesized. With peak fluorescence emissions at approximately 700 or 800 nm,
these molecules can be used for fluorescence-assisted resection and exploration
(FLARE) dual-channel imaging. Longitudinal FLARE studies in mice demonstrate that
phosphonated near-infrared fluorophores remain stable in bone for over five
weeks, and histological analysis confirms their incorporation into the bone
matrix. Taken together, a new strategy for creating ultra-compact, targeted near
infrared fluorophores for various bioimaging applications is described.
PMID- 25139081
TI - Kinetics of primary bile acids in patients after proctocolectomy and ileal pouch
anal anastomosis.
AB - BACKGROUND: The high incidence of cholesterol gallstones in patients after
proctocolectomy with ileal pouch-anal anastomosis (IPAA) may be due to an
increased loss of bile acids. We aimed to evaluate the kinetics of the primary
bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) in these patients.
METHODS: Pool sizes, synthesis rates, and fractional turnover rates of CA and
CDCA were determined by combined capillary gas chromatography/isotope ratio mass
spectrometry in serum samples after administration of [13C]CA and [13C]CDCA in 6
patients and 9 healthy volunteers. RESULTS: In patients with IPAA, pool sizes of
CA and CDCA were 11.5 (8.2-23.8) and 12.1 (6.7-20.1) umol/kg, respectively, and
were significantly lower than in healthy controls [36.0 (24-47) and 29.0 (21-42)
umol/kg, respectively; p < 0.05, each]. Fractional turnover rates of CA [1.19
(1.06-1.82) vs. 0.31 (0.13-0.54) per day] and CDCA [1.01 (0.50-1.63) vs. 0.23
(0.09-0.36) per day] were increased fourfold in patients with IPAA (p < 0.05,
each). Synthesis rates of CDCA [10.2 (5.2-32.9) vs. 6.6 (2.7-10.5) umol/kg per
day, p = 0.05] and CA [15.1 (9.3-39.4) vs. 11.5 (3.1-20.5) umol/kg per day, n.s.]
tended to be higher in patients with IPAA than in controls. CONCLUSION: The
reduced pool size of primary bile acids may contribute to the high incidence of
cholesterol gallstones in patients after proctocolectomy and IPAA.
PMID- 25139082
TI - Azithromycin hydrates-implications of processing-induced phase transformations.
AB - According to label claims, in commercial solid dosage forms, azithromycin (AZI)
exists either as a monohydrate (MH) or as a dihydrate (DH). Although these two
forms are known to be relatively stable in the solid state, AZI sesquihydrate
(SH) was observed in a drug product. This was believed to be a consequence of a
processing-induced phase transformation. Our goal was to prepare and characterize
AZI SH and map its solid-state transition pathways with other AZI phases. When
dehydrated at temperatures <80 degrees C, DH yielded an isomorphic dehydrate,
whereas dehydration at >=80 degrees C yielded SH. Heating SH to 100 degrees C or
holding at 0% RH at room temperature, yielded an amorphous product through an
intermediate isomorphic dehydrate, isostructural to SH. On the other hand,
dehydration of MH (at >=60 degrees C) resulted in amorphization with no
intermediate crystalline anhydrate. Diagnostic XRD peaks of AH, MH, SH, and DH
enabled their unambiguous identification. However, the presence of crystalline
excipients hindered active pharmaceutical ingredient characterization in drug
product. Pattern subtraction method was used to selectively remove the
contribution of the crystalline excipients to the overall diffraction pattern,
thereby facilitating the physical characterization of AZI in the drug product.
PMID- 25139083
TI - Controlling radiation exposure in interventional cardiology.
PMID- 25139084
TI - Noncardiac surgery after coronary revascularization: more contemporary evidence
needed.
PMID- 25139085
TI - Reconciling poststenotic pressure with hyperemic flow: comparing coronary flow
reserve, instantaneous wave-free ratio, and fractional flow reserve.
PMID- 25139086
TI - Torrent of troponin.
PMID- 25139087
TI - How to move toward the least invasive transfemoral transcatheter aortic valve
implantation procedure?
PMID- 25139088
TI - Mechanisms by which transradial approach may reduce mortality in ST-segment
elevation myocardial infarction.
PMID- 25139089
TI - Delayed and fatal embolization of a left atrial appendage closure device.
PMID- 25139090
TI - Unanticipated pseudocoarctation highlights the importance of visualizing aortic
arch anatomy before transfemoral transcatheter aortic valve implantation.
PMID- 25139091
TI - Response to letter regarding, "administration of a loading dose has no additive
effect on platelet aggregation during the switch from ongoing clopidogrel
treatment to ticagrelor in patients with acute coronary syndrome".
PMID- 25139093
TI - Identification of miRNAs as potential new biomarkers for nervous system cancer.
AB - Several recent studies have indicated the possibility of detecting dysregulated
microRNAs (miRNAs) to diagnose nervous system cancer (NSC). Our study was
conducted to explore the clinical applicability of miRNAs as potential ideal
biomarkers for the diagnosis of NSC. For this meta-analysis, a systematic
literature search was conducted in the Embase, Medline, Cochrane, Wangfang, and
Sinomed databases. A standard quality tool-quality assessment of diagnostic
accuracy studies was employed to assess the quality of the included studies.
Specificity, sensitivity, diagnostic odds ratio (DOR), and area under curve (AUC)
were pooled to assess overall test accuracy. In total, 25 studies from 7
articles, including 388 patients with NSC and 435 controls (healthy controls and
patients with neurologic disorders), were included in this meta-analysis. For the
studied miRNAs, the pooled sensitivity, specificity, and DOR for predicting NSC
were 85% (95% confidence interval [CI] 80-89%), 85% (95% CI 80-89%), and 32 (95%
CI 19-55), respectively. The pooled AUC for miRNAs identifying NSC was 0.92. In
addition, results from subgroup analyses indicated that using miRNA panels yield
a much better diagnostic accuracy when compared with using a particular miRNA.
The current evidence suggests that miRNAs, especially miRNA panels on body
fluids, may be suitable for use as diagnostic biomarkers for NSC patients.
However, more prospective studies using larger cohorts should be conducted to
confirm their degree of accuracy.
PMID- 25139094
TI - Reduction of alpha-dystroglycan expression is correlated with poor prognosis in
glioma.
AB - Dystroglycan (DG), a multifunctional protein dimer of non-covalently linked alpha
and beta subunits, is best known as an adhesion and transduction molecule linking
the cytoskeleton and intracellular signaling pathways to extracellular matrix
proteins. Loss of DG binding, possibly by degradation or disturbed glycosylation,
has been reported in a variety of cancers. DG is abundant at astroglial endfeet
forming the blood-brain barrier (BBB) and glia limitans; so, we examined if loss
of expression is associated with glioma. Expression levels of alpha-DG and beta
DG were assessed by immunohistochemistry in a series of 78 glioma specimens to
determine the relationship with tumor grade and possible prognostic significance.
alpha-DG immunostaining was undetectable in 44 of 49 high-grade specimens (89.8%)
compared to 15 of 29 low-grade specimens (51.72%) (P<0.05). Moreover, loss of
alpha-DG expression was an independent predictor of shorter disease-free survival
(DFS) (hazards ratio (HR) = 0.142, 95% confidence interval (CI) 0.033-0.611,
P=0.0088). Reduced expression of both alpha-DG and beta-DG was also a powerful
negative prognostic factor for DFS (HR=2.556, 95% CI 1.403-4.654, P=0.0022) and
overall survival (OS) (HR=2.193, 95% CI 1.031-4.666, P=0.0414). Lack of alpha-DG
immunoreactivity is more frequent in high-grade glioma and is an independent
predictor of poor clinical outcome. Similarly, lack of both alpha-DG and beta-DG
immunoreactivity is a strong independent predictor of clinical outcome.
PMID- 25139095
TI - Collagen triple helix repeat containing 1 (Cthrc1) is an independently prognostic
biomarker of non-small cell lung cancers with cigarette smoke.
AB - Collagen triple helix repeat containing 1 (Cthrc1) has been recently documented
in various malignancies, but its role in non-small cell lung cancer (NSCLC)
remains uncertain. In the current study, we investigated the level of Cthrc1 in
NSCLC tissues by immunohistochemistry. Results revealed that Cthrc1
overexpression was significantly associated with differentiation (P=0.039), tumor
node-metastasis (TNM) stage (P=0.035), lymph node status (P=0.001), and cigarette
smoke (P=0.037). Furthermore, it was shown that patients with high Cthrc1
expression had significantly poorer overall survival (OS) and disease-free
survival (DFS; P=0.004 and P=0.010, respectively). Interestingly, high Cthrc1
expression was an independent prognostic factor for both OS and DFS (P=0.010 and
P=0.005, respectively) only in NSCLCs with cigarette smoke. These results
indicated and suggested that Cthrc1 could be used as a prognostic marker for
NSCLC, and it may play an important role in the smoked-related NSCLC.
PMID- 25139096
TI - Primary epidural hemangiopericytoma in the sacrum: a rare case and literature
review.
AB - Hemangiopericytoma (HPC) is an uncommon highly vascular neoplasm that originated
from Zimmerman's pericytes which surrounds the endothelial tissue. Primary
epidural HPC of the sacrum is extremely rare. We reported an unusual case of
primary epidural malignant HPC of the sacrum that invaded vertebral bone and
caused rectum compression in a 57-year-old male for the first time. The patient
presented progressive low back pain and ribbon-like stool over 3 months. The
surgical intervention involved sacrectomy and en bloc resection of the tumor. We
described the clinical, radiological, and histological features of this tumor and
reviewed the literature.
PMID- 25139092
TI - Regulation of male sex determination: genital ridge formation and Sry activation
in mice.
AB - Sex determination is essential for the sexual reproduction to generate the next
generation by the formation of functional male or female gametes. In mammals,
primary sex determination is commenced by the presence or absence of the Y
chromosome, which controls the fate of the gonadal primordium. The somatic
precursor of gonads, the genital ridge is formed at the mid-gestation stage and
gives rise to one of two organs, a testis or an ovary. The fate of the genital
ridge, which is governed by the differentiation of somatic cells into Sertoli
cells in the testes or granulosa cells in the ovaries, further determines the sex
of an individual and their germ cells. Mutation studies in human patients with
disorders of sex development and mouse models have revealed factors that are
involved in mammalian sex determination. In most of mammals, a single genetic
trigger, the Y-linked gene Sry (sex determination region on Y chromosome),
regulates testicular differentiation. Despite identification of Sry in 1990,
precise mechanisms underlying the sex determination of bipotential genital ridges
are still largely unknown. Here, we review the recent progress that has provided
new insights into the mechanisms underlying genital ridge formation as well as
the regulation of Sry expression and its functions in male sex determination of
mice.
PMID- 25139098
TI - Lymph node ratio as an independent prognostic indicator in stage III colorectal
cancer: especially for fewer than 12 lymph nodes examined.
AB - Although nodal invasion represents one of the most powerful prognostic indicators
in colorectal cancer (CRC), marked heterogeneity exists within stage III
patients. Lymph node ratio (LNR) may offer more precise prognostication in stage
III CRC. The aim of this study is to investigate the prognostic impact of LNR on
survival in stage III CRC patients. We retrospectively reviewed the data of 288
consecutive patients who underwent radical resection for stage III CRC between
January 2000 and December 2008 in the Gastrointestinal Surgery Department, Peking
University People's Hospital. The patients were divided into three groups
according to LNR quartiles: LNR < 0.167 (n=72), 0.167 <= LNR < 0.562 (n = 140),
and LNR >= 0.562 (n=76). The association between overall survival (OS) and
disease-free survival (DFS) and 11 variables including age, gender, tumor
location, size, grade, histology, tumor (T) stage, number of metastatic LNs, and
LNR was analyzed by multivariate analysis. Survival curves were plotted by the
Kaplan-Meier method. Both LNR and the number of metastatic LNs were significant
prognostic factors for 5-year DFS and OS in stage III CRC patients. LNR was an
independent prognostic factor for 5-year OS. LNR remained an independent
prognostic factor in patients with fewer than 12 lymph nodes examined. LNR was a
potent independent prognostic predictor for OS and DFS in stage III CRC patients,
especially for patients with fewer than 12 lymph nodes examined.
PMID- 25139099
TI - Prognostic role of microRNA-31 in various cancers: a meta-analysis.
AB - To date, many studies have shown that microRNAs (miRNA) exhibit altered
expression levels in various cancers and may play a potential role as diagnostic
and prognostic biomarkers of cancers. This meta-analysis was designed to evaluate
the exact role of microRNA-31 (miR-31) for survival and discuss the possibility
of utilizing miR-31 to predict the prognosis of patients with various human
cancers. Electronic literature databases including PubMed, Web of Science, and
Embase were searched for articles published until May 2014. The articles only
written in English were considered. Data were extracted from studies comparing
overall survival (OS), cancer-specific survival (CSS), or postoperative survival
(PS) in patients with multiple cancers, which showed higher miR-31 expression
than with similar patients. Pooled hazard ratios (HRs) of miR-31 for survival and
95 % confidence intervals (CI) were calculated. Ten studies with a total of 1,648
participants were included for the meta-analysis. For OS, the pooled HRs of
higher miR-31 expression in cancers indicated significant predictor poorer
survival in general cancers in either univariate analysis (HR=2.34, 95 % CI=1.15
3.52, P<0.05) or multivariate analysis (HR=1.15, 95 % CI=1.04-1.26, P<0.05). For
CSS, elevated miR-31 was also a significant predictor to general cancers in
multivariate analysis (HR=1.77, 95 % CI=1.06-2.47, P<0.05). And, no association
was found between miR-31 expression and PS. In conclusion, the present findings
indicate that high miR-31 expression is associated with poor OS and CSS in
patients with general cancers and miR-31 may be a useful clinical prognostic
biomarker.
PMID- 25139097
TI - Role of novel and GWAS originated PLCE1 genetic variants in susceptibility and
prognosis of esophageal cancer patients in northern Indian population.
AB - Recent genome-wide association studies (GWAS) have identified variants in
phospholipase C epsilon1 (PLCE1) as novel susceptibility markers for esophageal
squamous cell carcinoma (ESCC) in Chinese population. Although few studies have
replicated this findings in other populations, but results are contradictory. So,
we aimed to replicate association of two previously reported non-synonymous
polymorphisms (rs2274223A>G and rs3765524C>T) from haplotype block 10 and
evaluated a novel variant (rs7922612C>T) from haplotype block 2 of PLCE1 with
susceptibility and prognosis of ESCC in northern Indian population. The
genotyping of PLCE1 variants were performed in 293 histopathologically confirmed
incident ESCC cases (including 177 follow-up cases) and 314 age-, gender-, and
ethnicity-matched controls using PCR RFLP. All statistical analyses were
performed through SPSS version 15.0. Modeling and functional prediction of two
non-synonymous variants were carried out using bioinformatics tools. PLCE1
polymorphisms were not associated with susceptibility to ESCC or its clinical
phenotypes (tumor location/lymph node metastasis). No interaction with
environmental risk factors was found. In silico analysis suggested negligible
effect on structure of PLCE1 protein due to PLCE1 rs2274223 (H1927R) and
rs3765524 (T1777I) polymorphisms. Survival analysis showed PLCE1 rs7922612CT + TT
genotype conferred adverse outcome to ESCC patients. Our study for the first time
suggests that GWAS originated PLCE1 variants do not have independent role in
susceptibility of ESCC in northern Indian population; however, a novel haplo
tagging SNP rs7922612 may modify survival outcome of ESCC patients.
PMID- 25139100
TI - Glycolytic activity with 18F-FDG PET/CT predicts final neoadjuvant chemotherapy
response in breast cancer.
AB - The purpose of the present study is to explore the relation between glycolytic
metabolism assessed by (18)F-fluoro-2-deoxy-D-glucose positron emission
tomography/computed tomography ((18)F-FDG PET/CT) and final neoadjuvant
chemotherapy (NC) response in locally advanced breast tumors. Of women with
breast cancer, 126 were prospectively evaluated. All patients underwent (18)F-FDG
PET/CT previous to NC. Standard uptake value (SUV) max was calculated in the
primary tumor. After NC, residual primary tumor specimen was histopathologically
classified according to Miller and Payne tumor regression grades (TRG), from G1
to G5 and in response groups as good responders (G4 or G5), partial responders
(G2 or G3), and non-responders (G1). Furthermore, residual lesions were
classified following a binary assessment as responders (G4 or G5) and non
responders (the rest of cases). The relationship between SUV max with TRG and
response groups was evaluated. Of tumors, 127 were assessed (a patient had
bilateral breast lesions). TRG were as follows: G1 (27), G2 (27), G3 (32), G4
(11), and G5 (30). Forty-one were classified as good responders, 59 as partial
responders, and 27 as non-responders. For the binary assessment, 41 lesions were
classified as responders and 86 as non-responders. We found statistical
differences (p=0.02) between the mean SUV max and TRG with greater SUV values for
G5 compared to the other TRG. Good responders showed greater mean SUV max +/- SD
compared to partial responders and non-responders (10.51 +/- 6.64 for good
responders, 6.94 +/- 5.81 for partial responders, and 5.23 +/- 2.76 for non
responders; p=0.001). Baseline tumor metabolism assessing by FDG PET/CT was
associated with the final histopathologic status after neoadjuvant chemotherapy,
with greater SUV max values for good responders compared to the less responder
cancers.
PMID- 25139101
TI - The preoperative lymphocyte to monocyte ratio predicts clinical outcomes in
patients with stage II/III gastric cancer.
AB - Recently, lymphocyte to monocyte ratio (LMR) has been reported to be associated
with clinical outcomes in some types of cancer but has not been explored in
gastric cancer. In this study, we analyzed the association between LMR and
clinical outcomes in stage II/III gastric cancer patients. Preoperative LMR
calculated from peripheral lymphocyte and monocyte with corresponding clinical
features from 426 stage II/III gastric cancer patients was noted. Kaplan-Meier
method and Cox regression model were applied for overall survival (OS) and
recurrence-free survival (RFS). Related with smaller tumor size (p<0.001),
increased LMR could predict better OS [hazard ratio (HR), 0.688; 95% confidence
interval (CI), 0.521-0.908, p=0.008] and was borderline significantly associated
with better RFS (HR, 0.775; 95% CI, 0.592-1.01, p=0.06) in stage II/III gastric
cancer patients through multivariable analysis. Subgroup analyses revealed that
except stage III patients for RFS which yielded borderline significance
(p=0.052), lower LMR was associated with poor clinical outcomes for patients
regardless of different stages or whether the patients received adjuvant
chemotherapy. The elevated preoperative LMR level was a significant favorable
factor in the prognosis of stage II/III gastric cancer patients, especially for
those with stage II. However, further validation of our findings is warranted.
PMID- 25139102
TI - The lncRNA-MYC regulatory network in cancer.
AB - Long non-coding RNAs (lncRNAs) have been widely studied in recent years, and
accumulating evidence identified lncRNAs as crucial regulators of various
biological processes, including cell cycle progression, chromatin remodeling,
gene transcription, and posttranscriptional processing. In addition, the fact
that lncRNAs interact with the MYC gene family in human carcinomas has been
discovered. This review summarizes the latest progress on the investigation of
lncRNAs and MYC, particularly focusing on the interplay between lncRNAs and MYC
in cancer to reveal the significance of lncRNA-MYC network in regulating
initiation, development, and metastasis of tumors. Further research and
collection of clinical data would provide a better understanding of lncRNA-MYC
network in cancer diagnosis and treatment.
PMID- 25139103
TI - EMMPRIN and ADAM12 in prostate cancer: preliminary results of a prospective
study.
AB - Extracellular metalloproteinase inducer (EMMPRIN) and a disintegrin and
metalloproteinase (ADAM12) play a major role in cancer invasion and metastasis
owing to the fact that they are directly related to the cell microenvironment and
extracellular matrix (ECM) degradation. The aim of this study was to search for
an answer to the question "whether the determination of EMMPRIN and ADAM12 values
especially in urine may be helpful for the early diagnosis of prostate cancer
without employing invasive methods" and also to check whether they may be useful
for the determination of the patients with high metastasis risk. Peripheral blood
and urine from 66 prostate cancer patients (40 local, 20 locally advanced, 6
metastatic) and 14 healthy controls were evaluated by enzyme-linked immunosorbent
assay (ELISA) method. Serum EMMPRIN and ADAM12 values of the patients were seen
to be statistically higher than the serum EMMPRIN and ADAM12 values of the
healthy controls (p=0.01 and p=0.001, respectively). The urine ADAM12 levels were
significantly higher in patients (p=0.013). No significant relationships were
found between urine EMMPRIN values of the patients and the healthy controls
(p>0.05). Positive correlation between urine EMMPRIN-urine ADAM12 tests was found
in total patients group (r=0.683, p=0.001). Our preliminary results revealed that
serum EMMPRIN and ADAM12 values and urine ADAM12 values may be useful markers in
prostate cancer therapy. Due to the high correlation between these two tests, we
are of the opinion that the use of urine ADAM12 in clinic may be sufficient and
favorable together with prostate-specific antigen (PSA) for treatment.
PMID- 25139104
TI - TriMatch comparison of the efficacy of FloSeal versus TachoSil versus no
hemostatic agents for partial nephrectomy: results from a large multicenter
dataset.
AB - OBJECTIVES: To evaluate the efficacy of hemostatic agents, TachoSil and FloSeal,
during partial nephrectomy using a large multicenter dataset. METHODS: Data of
1055 patients who underwent partial nephrectomy between January 2009 and December
2012 in 19 Italian centers were collected within an observational multicentric
study (RECORd Project). The decision whether or not to use hemostatic agents
after renorrhaphy and the type of hemostatic agents applied was adopted according
to the centers' and surgeons' preference. A TriMatch propensity score analysis
was applied to balance three study groups (no hemostatic agents, TachoSil,
FloSeal) for sex, age, surgical indication (elective/relative vs imperative),
clinical stage (cT1a vs cT1b), tumor exophyticity, approach (open vs minimally
invasive), technique (standard partial nephrectomy vs simple enucleation),
preoperative hemoglobin and creatinine. Postoperative complications and variation
of hemoglobin and creatinine values between preoperative versus third
postoperative day were compared. RESULTS: TriMatch analysis allowed us to obtain
66 well-balanced triplets. No differences were found in terms of outcomes between
the study groups. CONCLUSIONS: The present findings suggest that adding
hemostatic agents to renorraphy during partial nephrectomy does not provide
better surgical outcomes.
PMID- 25139105
TI - HES1 as an independent prognostic marker in esophageal squamous cell carcinoma.
AB - BACKGROUND: Notch signaling is one of the main involved pathways in cell
differentiation and organogenesis, and its deregulation may lead to
tumorigenesis. In this pathway, targeted to the CSL (CBF1, Suppressor of Hairless
or Lag-1) complex, notch intracellular domain (NICD) releases corepressors and
recruits MAML1 as coactivator triggering the activation of notch signaling
transcription complex. Hairy enhance of split-1 (HES1) is one of the notch
signaling target genes which is a basic helix-loop-helix (bHLH) transcription
factor acting as a proliferation stimulator through the suppression of cell cycle
inhibitors such as p27 and p21. AIMS: In this study, we aimed to analyze the role
of HES1 in the progression of esophageal squamous cell carcinoma (ESCC). METHODS:
Messenger RNA (mRNA) expression of HES1 in fresh tumoral tissues and their margin
normal samples were assessed in 50 ESCC patients by real-time polymerase chain
reaction (RT-PCR). RESULTS: Thirteen out of 50 cases (26 %) had HES1
underexpression, while HES1 overexpression was observed only in 4 (8 %) samples.
HES1 underexpression was significantly correlated with tumor depth of invasion (P
= 0.035). CONCLUSION: Although we have not observed any significant correlation
between the HES1 expression and notch activation in ESCC, this study is the first
report that elucidated the HES1 underexpression in ESCC and revealed its
correlation with the invasiveness of ESCC.
PMID- 25139106
TI - Does multifunctionality matter to US farmers? Farmer motivations and conceptions
of multifunctionality in dairy systems.
AB - The concept of multifunctionality describes and promotes the multiple non
production benefits that emerge from agricultural systems. The notion of
multifunctional agriculture was conceived in a European context and largely has
been used in European policy arenas to promote and protect the non-production
goods emerging from European agriculture. Thus scholars and policy-makers
disagree about the relevance of multifunctionality for United States agricultural
policy and US farmers. In this study, we explore lived expressions of
multifunctional agriculture at the farm-level to examine the salience of the
multifunctionality concept in the US. In particular, we investigate rotational
grazing and confinement dairy farms in the eastern United States as case studies
of multifunctional and productivist agriculture. We also analyze farmer
motivations for transitioning from confinement dairy to rotational grazing
systems. Through interviews with a range of dairy producers in Wisconsin,
Pennsylvania, and New York, we found that farmers were motivated by multiple
factors--including improved cow health and profitability--to transition to
rotational grazing systems to achieve greater farm-level multifunctionality.
Additionally, rotational grazing farmers attributed a broader range of production
and non-production benefits to their farm practice than confinement dairy
farmers. Further, rotational grazing dairy farmers described a system-level
notion of multifunctionality based on the interdependence of multiple benefits
across scales--from the farm to the national level--emerging from grazing
operations. We find that the concept of multifunctionality could be expanded in
the US to address the interdependence of benefits emerging from farming
practices, as well as private benefits to farmers. We contend that understanding
agricultural benefits as experienced by the farmer is an important contribution
to enriching the multifunctionality concept in the US context, informing agri
environmental policy and programs, and ultimately expanding multifunctional
agricultural practice in the US.
PMID- 25139107
TI - Montreal Cognitive Assessment (MoCA)-Italian version: regression based norms and
equivalent scores.
AB - The Montreal Cognitive Assessment (MoCA) is a brief cognitive screening
instrument developed by Nasreddine et al. to detect mild cognitive impairment, a
high-risk condition for Alzheimer's disease and other forms of dementia. In this
study we report normative data on the MoCA-Italian version, collected on a sample
of 225 Italian healthy subjects ranged in age between 60 and 80 years, and in
formal education from 5 to 23 years. The global normal cognition was established
in accordance with the Mini-Mental State Examination score and with the Prose
Memory Test score (Spinnler and Tognoni, Ital J Neurol Sci 6:25-27, 1987). None
of the participants had a history of psychiatric, neurological, cerebrovascular
disorders or brain injury or took drugs affecting cognition. Linear regression
analysis was performed to evaluate the potential effect of age, education and sex
on the MoCA total performance score. We provide correction grids to adjust raw
scores and equivalent scores with cut-off value to allow comparison between MoCA
performance and others neuropsychological test scores that can be administered on
the same subject.
PMID- 25139108
TI - Are atraumatic spinal needles as efficient as traumatic needles for lumbar
puncture?
AB - The most frequent complication of lumbar puncture is post lumbar puncture
headache (PLPH). Recent studies confirmed that the use of atraumatic spinal
needles significantly reduces the risk of PLPH. However, the majority of
neurologists still use traumatic needles, possibly caused by misconceptions and
beliefs about practical performance of atraumatic spinal needles. Therefore, we
investigated the practical characteristics of atraumatic and traumatic spinal
needles. An experimental setup with a fluid column was used with (1) a
physiological NaCl 0.9 % solution and (2) a high protein content solution. Flow
rates and duration of pressure measurements were measured using a traumatic
needle and an atraumatic needle. The average flow rate differed less than 10 %
between the two needle types with NaCl solution, and for the high protein
solution the difference was even smaller. Time taken to perform accurate pressure
measurements did not differ between the two needle types using NaCl 0.9 %, and
was even slightly shorter for the atraumatic needle when using the high protein
solution. Average flow rates and duration of pressure measurements are comparable
between atraumatic spinal needles and traumatic needles. Therefore, these
performance characteristics are no reason to favor traumatic needles over
atraumatic needles.
PMID- 25139109
TI - TLR4 enhances histamine-mediated pruritus by potentiating TRPV1 activity.
AB - BACKGROUND: Recent studies have indicated that Toll-like receptor 4 (TLR4), a
pathogen-recognition receptor that triggers inflammatory signals in innate immune
cells, is also expressed on sensory neurons, implicating its putative role in
sensory signal transmission. However, the possible function of sensory neuron
TLR4 has not yet been formally addressed. In this regard, we investigated the
role of TLR4 in itch signal transmission. RESULTS: TLR4 was expressed on a
subpopulation of dorsal root ganglia (DRG) sensory neurons that express TRPV1. In
TLR4-knockout mice, histamine-induced itch responses were compromised while TLR4
activation by LPS did not directly elicit an itch response. Histamine-induced
intracellular calcium signals and inward currents were comparably reduced in TLR4
deficient sensory neurons. Reduced histamine sensitivity in the TLR4-deficient
neurons was accompanied by a decrease in TRPV1 activity. Heterologous expression
experiments in HEK293T cells indicated that TLR4 expression enhanced capsaicin
induced intracellular calcium signals and inward currents. CONCLUSIONS: Our data
show that TLR4 on sensory neurons enhances histamine-induced itch signal
transduction by potentiating TRPV1 activity. The results suggest that TLR4 could
be a novel target for the treatment of enhanced itch sensation.
PMID- 25139111
TI - Need of standardization in bariatric surgery: is it time to think about? Comment
on Contreras J E, Santander C, Court I, Bravo J. Correlation between age and
weight loss after bariatric surgery. Obesity Surgery 2013; 23(8):1286-9.
PMID- 25139110
TI - Comparison between rapid and mixed maxillary expansion through an assessment of
dento-skeletal effects on posteroanterior cephalometry.
AB - BACKGROUND: The aim of this study is to compare the dento-skeletal effects of
rapid maxillary expansion (RME) and mixed maxillary expansion (MME), assessed on
posteroanterior (PA) cephalograms. METHODS: Treatment groups consisted of 42
patients; mean age in RME group (n = 21,13 female and 8 male subjects) was 8.8
years +/- 1.37 at T0 and 9.6 years +/- 1.45 at T1 and mean age in MME group (n =
21, 12 female and 9 male patients) was 8.9 years +/- 2.34 at T0 and 10.5 years +/
2.08 at T1. Seventeen bilateral anatomic landmarks, 16 linear (12 skeletal and 4
dental) and 4 angular measurements were assessed for each patient at T0 and T1.
Data from the two groups were compared using independent sample t test (p <
0.05). RESULTS: At T0, the groups were similar for all examined variables (p >
0.05). Significant and equal increase of lateronasal and maxillary and upper and
lower molar widths (p < 0. 01) occurred in both groups at T1. Significant but
different increases were observed for maxillary incisal, upper left first molar
lateroorbitale, and maxillary first molar angles (p < 0.001 vs. p < 0.05).
Significant increases were reported for upper inter-incisal width apex (p <
0.001) and upper right first molar-lateroorbitale angle (p < 0.05) only in the
RME group. At T1, differences in maxillary incisal angle (p < 0.05), upper left
first molar-lateroorbitale, and maxillary first molar angles (p < 0.001) were
noted. CONCLUSIONS: RME and MME were both effective to increase skeletal
transverse dimensions by opening mid-palatal suture in growing patients, while
MME was associated with minor dental side effects than RME.
PMID- 25139112
TI - Deficits in anticipatory but not consummatory pleasure in people with recent
onset schizophrenia spectrum disorders.
AB - The majority of studies examining self-reported anticipatory and consummatory
pleasure in schizophrenia, as measured on the Temporal Experience of Pleasure
Scale (TEPS), have been conducted on chronically ill people with the disorder. In
this study, people with a recent-onset schizophrenia spectrum diagnosis (first
psychotic episode within one year of study participation) (n=88) and people
without a schizophrenia spectrum diagnosis (n=66) were administered the TEPS.
People with a schizophrenia spectrum diagnosis reported significantly lower
scores of anticipatory, but not consummatory, pleasure on the TEPS compared to
the control group. TEPS anticipatory pleasure scores were also significantly,
negatively correlated with negative symptoms, but neither TEPS anticipatory nor
consummatory pleasure scores were significantly correlated with functioning
measures. Our results replicate previous findings with chronically ill people
with schizophrenia on the TEPS.
PMID- 25139113
TI - Effects of COMT genotype on cognitive ability and functional capacity in
individuals with schizophrenia.
AB - Cognitive and functional impairments are core features of schizophrenia. This
study examined the catechol-O-methyltransferase (COMT) genotype and its
relationship to cognition and functional capacity in 188 individuals with
schizophrenia or schizoaffective disorder. We found that in a dose-response
fashion, individuals with more Met alleles performed significantly better on
tests of learning/memory and abstraction. The effects of COMT genotype on
cognition were modest, explaining about 3% of the variance in learning/memory and
abstraction. Larger studies will be needed to examine the relationships between
COMT and other genes and cognitive performance and everyday functioning.
PMID- 25139115
TI - Towards a solution of the wires' slippage problem of the Ilizarov external
fixator.
AB - Clinical experience has indicated that many complications during treatment with
the Ilizarov method, and mainly tract infection, are related to decreased wire
tension. The aim of this work was to evaluate biomechanically a novel wire
tensioning and clamping system that will minimise or even diminish the reduction
of the wire pretension during treatment. The proposed approach is based on
threading of the wire end in a sufficient length. The wire pretension is applied
by twisting a nut on the threaded part of the wires against the ring and is
recorded by an incorporated force sensor. For biomechanical evaluation, the
frame, consisting of a polyethylene bar, simulating the bone fragment, suspended
on two rings, was subjected to a dynamic load of 0-800 N at a frequency of 0.5
Hz. After dynamic loading for 20 min, loss of the initial wire pretension for the
novel clamping system ranged between 12 and 16%. The average loss for
conventionally clamped wires was 75%. The advantages of the novel clamping system
were the much greater ability to sustain the transverse load and the easy and
effectual wire re-tensioning. Although wire slippage has been avoided with the
novel system, wire material yield is still responsible for a pretension loss.
PMID- 25139114
TI - Comparative analysis of pedicular vascular control techniques during laparoscopic
nephrectomy: en bloc stapling or separate ligation?
AB - OBJECTIVE: To compare the safety and efficacy of en bloc stapling and separate
ligation techniques for renal vascular control during laparoscopic nephrectomy.
PATIENTS AND METHODS: Clinical data were collected from 60 patients who underwent
laparoscopic nephrectomies using en bloc stapling (n = 27, group 1) or the
separate ligation method (n = 33, group 2). Comparative analysis was carried out
between the two groups, examining operative times, blood loss, intra- and
postoperative complications and hospital stay. RESULTS: Compared with the
separate ligation method, the en bloc hilar control technique was associated with
a shorter total operating time (98 vs. 121 min, p = 0.029). However, both groups
were similar in terms of estimated blood loss, hemoglobin drop, changes in
creatinine level and postoperative hospital stay. The total complication rates in
group 1 and 2 were 3.7 and 15.1%, respectively, with a statistically significant
difference. There were no complications related to the use of the endo-GIA
stapler and no patients required conversion to open surgery in group 1. In group
2, 2 patients required conversion to open surgery, including 1 due to renal vein
bleeding secondary to inaccurate vascular control and the other due to bleeding
from the vena cava during dissection. In addition, 1 patient had a superficial
bowel injury that was repaired laparoscopically and another had a superficial
liver tear that was managed without conversion or transfusion. CONCLUSION: En
bloc ligation of the renal hilum is an easy and reliable technique that allows
safe and fast control of the renal pedicle.
PMID- 25139116
TI - Impact of baseline microbiological status on clinical outcomes in generalized
aggressive periodontitis patients treated with or without adjunctive amoxicillin
and metronidazole: an exploratory analysis from a randomized controlled clinical
trial.
AB - AIM: To explore whether subjects harbouring A. actinomycetemcomitans, P.
gingivalis or T. forsythia at baseline showed increased clinical benefits with
the adjunctive use of systemic amoxicillin and metronidazole (AMX-MET) during non
surgical treatment of generalized aggressive periodontitis (GAgP). MATERIAL AND
METHODS: Forty one subjects were included in this 6-month randomized placebo
controlled clinical trial using a 7-day course of systemic AMX-MET or placebo as
adjuncts to non-surgical periodontal therapy. Clinical and microbiological
parameters were collected at baseline, 2 and 6 months after treatment.
Microbiological cultures were processed for pooled subgingival samples and
identities of isolates were determined by PCR for A. actinomycetemcomitans, P.
gingivalis and T. forsythia RESULTS: At 6 months, the test treatment resulted in
significant additional improvements in the primary outcome variable compared to
placebo, and the effect of the adjunctive antimicrobials was not modified by the
baseline microbiological status in the primary analysis. However, secondary
exploratory subgroup analyses showed improved clinical outcomes in subjects
harbouring A. actinomycetemcomitans at baseline compared to subjects who did not
harbour this pathogen. CONCLUSIONS: All subjects benefited from the tested
adjunctive antimicrobial regimen, although subjects who harboured A.
actinomycetemcomitans at baseline may show greater clinical benefits. Larger
appropriately powered studies are needed to confirm whether adjunctive AMX-MET is
more beneficial for GAgP patients who harbour A. actinomycetemcomitans, along
with other key periodontal pathogens.
PMID- 25139117
TI - The nonaspanins TM9SF2 and TM9SF4 regulate the plasma membrane localization and
signalling activity of the peptidoglycan recognition protein PGRP-LC in
Drosophila.
AB - Transmembrane 9 (TM9) proteins, or nonaspanins, are a family of proteins
conserved throughout evolution and characterized by 9 transmembrane domains. In
Drosophila, TM9 superfamily protein member 4 (TM9SF4) and its closest paralogue,
TM9SF2, contribute to phagocytosis of various types of particles, while TM9SF4
displays non-redundant requirement in Gram-negative bacteria engulfment. In
addition, the two TM9 proteins control the actin cytoskeleton in larval
haemocytes and in Drosophila S2 cells. Here, we show that TM9SF4 and TM9SF2 co
immunoprecipitate with the peptidoglycan recognition protein (PGRP)-LC, which
triggers the Drosophila immune response to bacterial infection. Furthermore, both
TM9 proteins co-localize with this receptor in intracellular vesicles and at the
plasma membrane in Drosophila S2 cells in culture and in the fly fat body.
Silencing TM9SF4 prevents plasma membrane localization of PGRP-LC, whereas
silencing TM9SF2 does not, which may account for the non-redundant role of TM9SF4
in phagocytosis of Gram-negative bacteria. Finally, we provide a set of data
suggesting that TM9 proteins can prevent inappropriate signalling from the
unstimulated receptor.
PMID- 25139118
TI - Assessment of coronary artery intimal thickening in patients with a previous
diagnosis of Kawasaki disease by using high resolution transthoracic
echocardiography: our experience.
AB - BACKGROUND: Kawasaki disease (KD) is a generalized systemic vasculitis of unknown
etiology involving medium and small size blood vessels, particularly the coronary
arteries. In these vessels a progressive stenosis may result from active
remodeling with an intimal proliferation and neoangiogenesis. The aim of our
study was to assess, by using high-resolution transthoracic 2D Echocardiography,
if subjects with a previous diagnosis of Kawasaki disease after several years
show a coronary intimal thickening, suggestive of a persistent cardiovascular
risk. METHODS: We assessed measurement of thickening, inner diameter and outer
diameter of coronary arteries using 2D Echocardiography (Philips E 33 with multy
frequency S8-3 and S12-4 probes) and examining the proximal portion of left main
coronary artery just above the aortic valve with parasternal short axis view.
RESULTS: We found a significant intimal thickening in patients with previous
Kawasaki disease compared to healthy controls. In particular, we noticed that
also subjects not suffering from coronary impairment in acute phase have higher
values of thickening than healthy controls, and this wall thickening may confer a
higher cardiovascular risk. CONCLUSIONS: Therefore we concluded that the
assessment of coronary artery thickening by high-resolution transthoracic 2D
Echocardiography may become an essential instrument to evaluate late
cardiovascular risk in subjects with a diagnosis of Kawasaki disease in
childhood.
PMID- 25139119
TI - Natural compounds in epigenetics: a current view.
AB - The successful treatment of many human diseases, including cancer, has come to be
considered a major challenge, as patient response to therapy is difficult to
predict. Recently, considerable efforts are being focused on the development of
new tools to meet the growing demand for personalized medicine. With few
exceptions, synthetic compounds have been unable to meet initial expectations for
their clinical use. The last twenty years have been characterized by the failure
of several drugs in advanced clinical development, possibly due to the
insufficient understanding of molecular pathways underlying their mechanism of
action. Although the biodiversity of compounds found in nature has been poorly
explored until now, the field of naturally occurring drugs is rapidly expanding.
Here, we review the current knowledge on the use of natural compounds with
particular emphasis on those that display a chromatin remodeling effect coupled
with anticancer action.
PMID- 25139120
TI - Chronic toxicity and carcinogenicity of semicarbazide hydrochloride in Wistar
Hannover GALAS rats.
AB - We performed a combined study to determine the chronic toxicity and
carcinogenicity of semicarbazide hydrochloride (SEM-HCl). Male and female Wistar
Hannover GALAS rats were fed a diet containing SEM-HCl at 0, 10, 50, and 250ppm
for 52weeks (10 rats/sex/group) or for 104weeks (50 rats/sex/group). Enlargement
of the knee joints was apparent in both sexes at 250ppm. Reduced body weight was
observed at 250ppm from week 76 only in males. SEM-HCl exerted no toxic effects
on hematology, serum biochemistry, or organ weights. Histopathologically,
disarrangement of chondrocytes accompanied by increased connective tissues, and
degeneration of articular cartilage were found in males at 50ppm and above and in
females at 250ppm. Mild changes in the elastic laminae were observed at 250ppm
for both sexes in the chronic toxicity study. There were no significant
intergroup differences in the incidences or types of any tumors. Taken together,
toxicological effects of chronic exposure to SEM-HCI mainly occurred in the bone,
cartilage, and aorta. Based on histopathological findings, the no-observed
adverse-effect-level was 10ppm in males and 50ppm in females (equal to
0.6mg/kg/day in males and 3.9mg/kg/day in females). SEM-HCl was not carcinogenic
in rats.
PMID- 25139121
TI - Toxicological in vitro and subchronic evaluation of LASSBio-596.
AB - LASSBio-596, 2-[4-(1,4-tiazinan-4-ylsulfonyl) phenylcarbamoyl] benzoic acid, is
an achiral compound containing a subunit carboxylic amide, was capable of
preventing induced mechanical and morphological changes in the lungs that
commonly caused the onset of asthma. Previous studies to determine the acute
toxicity of oral LASSBio-596 at dose of 2000mg/kg caused no deaths in any of the
tested animals. To further evaluate the safety of LASSBio-596, in vitro and in
vivo tests were carried out. Regarding to in vitro test were used renal, hepatic,
pulmonary, cardiac, neurologic and intestinal cell lines. They were evaluated
using neutral red (NR) and [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide] (MTT) assays. Micronuclei also was performed. Concerning to in vivo was
performed subchronic on Wistar rats at doses of 10, 50, and 250mg/kg and
zebrafish test. The in vitro tests results showed the safety of LASSBio-596.
However, subchronic toxicity study results revealed changes in the blood
parameters of amylase, alanine aminotransferase (ALT), aspartate aminotransferase
(AST), glucose and creatine kinase (CK) which is used for cardiotoxicity
evaluation, although, did not identify any histopathological alterations.
However, zebrafish test demonstrated cardiac damage. It was impossible to
estimate the no-observed-adverse-effect-levels and lowest observed-adverse-effect
level due to the presence of cardiotoxicity in all tested doses.
PMID- 25139122
TI - Investigation of the MICs of fidaxomicin and other antibiotics against Hungarian
Clostridium difficile isolates.
AB - The aim of this study was to investigate in vitro activities of fidaxomicin and
other antibiotics against 188 Clostridium difficile strains collected from
different centers of Hungary. C. difficile isolates showed minimum inhibitory
concentration (MIC) range for fidaxomicin of <=0.008-0.5 mg/L, with a MIC90 of
0.125 mg/L. Only four isolates (2.1%) had 0.5 mg/L MIC to fidaxomicin. The
obtained MICs showed identical distribution to those found in the EUCAST database
for wild-type strains.
PMID- 25139123
TI - Intra-genomic variation in G + C content and its implications for DNA stable
isotope probing.
AB - Combining deoxyribonucleic acid (DNA-based) stable isotope probing (DNA-SIP) with
high-throughput sequencing provides a powerful culture-independent means to link
microbial metabolic function to genomic information and taxonomic identity. DNA
buoyant density (BD) in isopycnic gradients is dependent on both isotope
incorporation and G + C content. G + C content varies across a genome but is
constrained at rrn operons; hence, the ability to resolve isotopically labelled
DNA from unlabelled DNA in SIP may vary between small subunit-ribosomal nucleic
acid (SSU rRNA) amplicon and shotgun-read sequencing applications. We tested this
hypothesis by evaluating the G + C content of genomic DNA fragments that
encompassed either an SSU rRNA template ('amplicon-fragments') or a shotgun read
template ('shotgun-fragments'). We find that, contrary to expectations, the BD
distribution of amplicon-fragments is non-normal and can be highly skewed.
Furthermore, the BD distribution of amplicon-fragments can differ substantially
from that of shotgun-fragments from the same genome. Our findings demonstrate the
impact of G + C content on the downstream applications of DNA-SIP, which will aid
in proper experimental design and the development of statistical tests to
accurately identify sequences derived from isotopically labelled DNA.
PMID- 25139124
TI - The impact of a tumor diagnosis on patients' attitudes toward advance directives.
AB - BACKGROUND: Although advance care planning and the completion of advance
directives (ADs) are important tools to avoid unwanted aggressive care once
patients have lost their decision-making capacity, only a minority of cancer
patients are admitted with completed ADs, and little is known about patients'
wishes regarding AD consultations. METHODS: For 1 year, every new patient
admitted to the hematology/oncology outpatient clinic of the University Hospital
Regensburg received a self-administered questionnaire comprising a self
evaluation of AD knowledge and questions about preferences regarding consultation
partners and the time of consultation. Disease-related data were collected from
medical records. Statistics were calculated with SPSS. RESULTS: Of the 500
questionnaires handed out, 394 (75%) were evaluable and analyzed. Twenty-eight
percent of the participants had completed an AD (living will or health care
proxy). Ninety-two percent of the participants without ADs had never received a
consultation offer from any professional involved. Only 20% perceived a clear
relation between cancer and AD consultations. More than 50% of the participants
without ADs were in favor of consultations 'now' or 'in a few weeks', while more
than 40% objected to AD consultations. CONCLUSIONS: Oncology patients have a
large unmet demand for AD consultations. However, a relevant percentage of these
patients object to AD consultations. Structured and early AD consultation offers
should be made, and early discussions about indications for aggressive treatment
should take place.
PMID- 25139126
TI - Cardiovascular risk associated with testosterone-boosting medications: a
systematic review and meta-analysis.
AB - INTRODUCTION: Recent reports have significantly halted the enthusiasm regarding
androgen-boosting; suggesting that testosterone supplementation (TS) increases
cardiovascular (CV) events. AREAS COVERED: In order to overcome some of the
limitations of the current evidence, the authors performed an updated systematic
review and meta-analysis of all placebo-controlled randomized clinical trials
(RCTs) on the effect of TS on CV-related problems. Out of 2747 retrieved
articles, 75 were analyzed, including 3016 and 2448 patients in TS and placebo
groups, respectively, and a mean duration of 34 weeks. Our analyses, performed on
the largest number of studies collected so far, indicate that TS is not related
to any increase in CV risk, even when composite or single adverse events were
considered. In RCTs performed in subjects with metabolic derangements a
protective effect of TS on CV risk was observed. EXPERT OPINION: The present
systematic review and meta-analysis does not support a causal role between TS and
adverse CV events. Our results are in agreement with a large body of literature
from the last 20 years supporting TS of hypogonadal men as a valuable strategy in
improving a patient's metabolic profile, reducing body fat and increasing lean
muscle mass, which would ultimately reduce the risk of heart disease.
PMID- 25139127
TI - Ceftolozane/tazobactam (CXA 201) for the treatment of intra-abdominal infections.
AB - During the mid-nineties, 95-97% of intra-abdominal infection (IAI)- associated
microbes were susceptible to commonly used antibiotics. Nowadays, in Gram
negative bacilli, beta-lactam resistance and the associated co-resistance to
other antibiotics leading to multidrug resistance is reaching crisis proportions.
This is a critical issue in the treatment of IAIs, especially for complicated
IAIs and for those of nosocomial origin in severely ill patients. In this
setting, this article reviews the place in the therapeutic armamentarium of
ceftolozane/tazobactam, a new cephalosporin/beta-lactamase inhibitor with good
activity against extended spectrum beta-lactamase producing Enterobacteriaceae,
with stability to AmpC beta-lactamases and good anti-pseudomonal activity being
stable against the most common resistance mechanisms driven by mutation in
Pseudomonas aeruginosa. A profound review of its in vitro activity, in vivo
efficacy in animal models, pharmacodynamics, pharmacokinetics, clinical efficacy
in clinical trials in complicated IAIs and safety data is performed.
PMID- 25139125
TI - Depression and risk of hospitalization for pneumonia in a cohort study of older
Americans.
AB - OBJECTIVE: The aim of this study is to determine if depression is independently
associated with risk of hospitalization for pneumonia after adjusting for
demographics, medical comorbidity, health-risk behaviors, baseline cognition and
functional impairments. METHODS: This secondary analysis of prospectively
collected data examined a population-based sample of 6704 Health and Retirement
Study (HRS) (1998-2008) participants>50years old who consented to have their
interviews linked to their Medicare claims and were without a dementia diagnosis.
The eight-item Center for Epidemiologic Studies Depression Scale and/or
International Classification of Disease, Ninth Revision, Clinical Modification
(ICD-9-CM) depression diagnoses were used to identify baseline depression. ICD-9
CM diagnoses were used to identify hospitalizations for which the principal
discharge diagnosis was for bacterial or viral pneumonia. The odds of
hospitalization for pneumonia for participants with depression relative to those
without depression were estimated using logistic regression models. Population
attributable fractions were calculated to determine the extent that
hospitalizations for pneumonia could be attributable to depression. RESULTS:
After adjusting for demographic characteristics, clinical factors, and health
risk behaviors, depression was independently associated with increased odds of
hospitalization for pneumonia (odds ratio [OR]: 1.28, 95% confidence interval
[95%CI]: 1.08, 1.53). This association persisted after adjusting for baseline
cognition and functional impairments (OR: 1.24, 95%CI: 1.03, 1.50). In this
cohort, 6% (95%CI: 2%, 10%) of hospitalizations for pneumonia were potentially
attributable to depression. CONCLUSION: Depression is independently associated
with increased odds of hospitalization for pneumonia. This study provides
additional rationale for integrating mental health care into medical settings in
order to improve outcomes for older adults.
PMID- 25139128
TI - A cross-sectional exploration of the personality traits of dietitians.
AB - BACKGROUND: Personality traits refer to habitual patterns of behaviour, thought
and emotions, and have been shown to influence health professionals' career
decisions, career development, job satisfaction and retention. There is an
opportunity to better understand and support the career pathways of dietitians by
exploring their personality traits. The two primary aspects of personality are:
(i) temperament traits, which determine automatic emotional responses to
experiences, and are generally stable over lifetime, and (ii) character traits,
which reflect personal goals and values, and tend to develop with life
experience. The present study explored the levels of temperament and character
traits of dietitians, as well as their relationship to demographic variables.
METHODS: The study comprised a cross-sectional online survey of 346 Australian
dietitians [95% female; mean (SD) age 32 (10) years; mean (SD) time since
graduation 7 (9) years]. Temperament and character traits were measured by the
Temperament and Character Inventory. Key demographic variables were measured to
describe career decisions and pathways of dietitians. Multivariate analyses of
variance was used to investigate the relationship between demographic variables
and personality traits. RESULTS: Levels of several traits were significantly
associated with gender, age and highest level of education. In comparison to the
general population, the dietitians displayed average levels of Novelty Seeking;
high levels of Harm Avoidance, Reward Dependence, Persistence, Self-Directedness
and Cooperativeness; and low levels of Self-Transcendence. CONCLUSIONS: The
dietitians in the present study displayed levels of personality traits that were
similar to other health professionals, although they differed from the general
population. These findings are the precursor to further work that may inform
recruitment strategies and career counselling in dietetics.
PMID- 25139130
TI - Interactions of N2O5 and related nitrogen oxides with ice surfaces: desorption
kinetics and collision dynamics.
AB - The detailed interactions of nitrogen oxides with ice are of fundamental interest
and relevance for chemistry in cold regions of the atmosphere. Here, the
interactions of NO, NO2, N2O4, and N2O5 with ice surfaces at temperatures between
93 and 180 K are investigated with molecular beam techniques. Surface collisions
are observed to result in efficient transfer of kinetic energy and trapping of
molecules on the ice surfaces. NO and NO2 rapidly desorb from pure ice with upper
bounds for the surface binding energies of 0.16 +/- 0.02 and 0.26 +/- 0.03 eV,
respectively. Above 150 K, N2O4 desorption follows first-order kinetics and is
well described by the Arrhenius parameters Ea = 0.39 +/- 0.04 eV and A =
10((15.4+/-1.2)) s(-1), while a stable N2O4 adlayer is formed at lower
temperatures. A fraction of incoming N2O5 reacts to form HNO3 on the ice surface.
The N2O5 desorption rates are substantially lower on pure water ice (Arrhenius
parameters: Ea = 0.36 +/- 0.02 eV; A = 10((15.3+/-0.7)) s(-1)) than on HNO3
covered ice (Ea = 0.24 +/- 0.02 eV; A = 10((11.5+/-0.7)) s(-1)). The N2O5
desorption kinetics also sensitively depend on the sub-monolayer coverage of
HNO3, with a minimum in N2O5 desorption rate at a low but finite coverage of
HNO3. The studies show that none of the systems with resolvable desorption
kinetics undergo ordinary desorption from ice, and instead desorption likely
involves two or more surface states, with additional complexity added by
coadsorbed molecules.
PMID- 25139129
TI - Evaluation of surface roughness and bond strength of quartz fiber posts after
various pre-treatments.
AB - PURPOSE: Debonding at the post-adhesive interface is a major problem for quartz
fiber posts. The objective of this study was to evaluate surface roughness and
bond strength of quartz fiber posts after various surface treatments. MATERIALS
AND METHODS: Sixty-six quartz fiber posts were randomly divided into six
experimental groups (n = 11) including group C, untreated (control); group SB,
sandblasted; group SC, silica coated; group HF, hydrofluoric acid-etched; group
N, Nd:YAG laser irradiated; group E, Er:YAG laser irradiated. Surface roughness
of the posts was measured before and after pre-treatment. They were then bonded
to resin cement and tensile bond strength was determined in a universal testing
machine. Furthermore, two-way ANOVA and post hoc comparison tests (alpha = 0.05)
were performed on all data. RESULTS: The highest mean force value was observed in
group SB and followed by group E. Tukey's HSD test showed that there was no
statistical difference between group SB and group E (p = 0.673). The highest mean
roughness value was observed in group SB and a significant difference was found
between group SB and all other groups (p < 0.001). This study reveals that
sandblasting and Er:YAG laser irradiation provided a significant increase in bond
strength between quartz fiber posts and resin cement. CONCLUSIONS: Sandblasting
or Er:YAG laser-irradiation of the surface of the quartz fiber post before
cementation is recommended for increasing retention.
PMID- 25139131
TI - Magnetic resonance imaging characteristics of equine head disorders: 84 cases
(2000-2013).
AB - The equine head is an anatomically complex area, therefore advanced tomographic
imaging techniques, such as computed tomography or magnetic resonance imaging
(MRI), are often required for diagnosis and treatment planning. The purpose of
this multicenter retrospective study was to describe MRI characteristics for a
large sample of horses with head disorders. Horses imaged over a period of 13
years were recruited. Eighty-four horses met the inclusion criteria, having
neurological (n = 65), sinonasal (n = 14), and soft tissue (n = 5) disorders.
Magnetic resonance imaging accurately depicted the anatomy and allowed
identification of the primary lesion and associated changes. There were good
correlations between MRI findings and intraoperative or postmortem results.
Magnetic resonance imaging showed the exact localization of the lesions, their
size, and relation to surrounding structures. However, in the neurological group,
there were 45 horses with no MRI abnormalities, 29 of which had a history of
recurrent seizures, related to cryptogenic epilepsy. Magnetic resonance imaging
was otherwise a valuable diagnostic tool, and can be used for studying a broad
range of head disorders using either low-field or high-field magnets.
PMID- 25139132
TI - Primary aerodigestive presentations of Pierre Robin sequence/complex and
predictive factors of airway type and management.
AB - OBJECTIVE: To document the mode and age of primary aerodigestive presentation of
Pierre Robin sequence/complex (PRS/C) children to the otolaryngologist and to
explore predictive factors of upper airway type and management. METHODS: This is
a retrospective cohort study conducted in a tertiary pediatric referral center. A
prospective surgical database was searched for children who were diagnosed with
PRS/C. Demographics, presenting complaint, secondary diagnoses, type of upper
airway obstruction, secondary airway lesions, presence of cleft palate, and
airway interventions were collected. Multiple linear regression analysis was
performed to predict upper airway obstruction type and intervention. RESULTS:
Seventy-seven potentially eligible patients were identified. Forty-six were
included (20 females). Mean age at presentation was 20.4+/-36.9 months (range 1
191.25 months). Twenty-three primarily presented with respiratory failure, 14
with sleep disordered breathing, and nine with swallowing dysfunction. Children
with presentations other than respiratory failure were older (p=0.004). Nineteen
were syndromic. Overt cleft palate was more common in those presenting with
respiratory failure (p=0.01). The type of airway obstruction encountered and use
of tracheostomy were positively predicted by the primary presenting feature of
respiratory failure (p<0.05) and male gender (p<0.05). CONCLUSION: A substantial
number of PRS/C patients present later than the neonatal period with
presentations other than respiratory failure. Both male gender and presentation
with respiratory failure predicted a more severe airway obstruction type and the
need for trachesotomy.
PMID- 25139133
TI - Hear here: children with hearing loss learn words by listening.
AB - OBJECTIVES: Early use of hearing devices and family participation in auditory
verbal therapy has been associated with age-appropriate verbal communication
outcomes for children with hearing loss. However, there continues to be great
variability in outcomes across different oral intervention programmes and little
consensus on how therapists should prioritise goals at each therapy session for
positive clinical outcomes. This pilot intervention study aimed to determine
whether therapy goals that concentrate on teaching preschool children with
hearing loss how to distinguish between words in a structured listening programme
is effective, and whether gains in speech perception skills impact on vocabulary
and speech development without them having to be worked on directly in therapy.
METHOD: A multiple baseline across subjects design was used in this within
subject controlled study. 3 children aged between 2:6 and 3:1 with moderate
severe to severe-profound hearing loss were recruited for a 6-week intervention
programme. Each participant commenced at different stages of the 10-staged
listening programme depending on their individual listening skills at
recruitment. Speech development and vocabulary assessments were conducted before
and after the training programme in addition to speech perception assessments and
probes conducted throughout the intervention programme. RESULTS: All participants
made gains in speech perception skills as well as vocabulary and speech
development. Speech perception skills acquired were noted to be maintained a week
after intervention. In addition, all participants were able to generalise speech
perception skills learnt to words that had not been used in the intervention
programme. CONCLUSIONS: This pilot study found that therapy directed at listening
alone is promising and that it may have positive impact on speech and vocabulary
development without these goals having to be incorporated into a therapy
programme. Although a larger study is necessary for more conclusive findings, the
results from this preliminary study are promising in support of emphasise on
listening skills within auditory-verbal therapy programmes.
PMID- 25139134
TI - Ketamine peritonsillar infiltration during tonsillectomy in pediatric patients:
An updated meta-analysis.
AB - OBJECTIVES: Peri-operative ketamine peritonsillar infiltration in children can
reduce the incidence of postoperative nausea and vomiting (PONV), but its
postoperative analgesic time is short. A previous meta-analysis in 2011 was
inconclusive due to insufficient data. Consequently, we updated the meta-analysis
to verify the role of ketamine peritonsillar infiltration for tonsillectomy in
pediatric patients. METHODS: Ten randomized controlled trials with a total of 522
cases were included. Pain intensity was measured by standard modified CHEOPS
score. RESULTS: The pain scores of ketamine group at 30 min and 60 min were
significantly lower than placebo group after surgery [weighted mean difference
(WMD) -1.20, 95% CI -2.20 to -0.19, P=0.02; WMD -1.71, 95% CI -2.12 to -0.22,
P=0.02]. Analgesic requirement in ketamine group were less than placebo group
[risk ratio (RR) 0.51, 95% CI 0.26-0.97; P=0.04]. Moreover, the incidence of PONV
was lower in ketamine group. (RR 0.73, 95% CI 0.54-0.97; P=0.03). However, there
were no differences between these two groups in operation time, anesthesia time,
first analgesic time and pain score at 120 min. CONCLUSIONS: Compared to placebo,
ketamine peritonsillar infiltration can relieve postoperative pain within one
hour but not at 120 min and reduces analgesic requirement and incidence of PONV.
Moreover, there was no difference in the first analgesic time.
PMID- 25139135
TI - Unique migration of a dental needle into the parapharyngeal space: successful
removal by an intraoral approach and simulation for tracking visibility in X-ray
fluoroscopy.
AB - OBJECTIVES: The first objective was to describe a novel case of migration of a
broken dental needle into the parapharyngeal space. The second was to address the
importance of simulation elucidating visualization of such a thin needle under X
ray fluoroscopy. METHODS: Clinical case records (including computed tomography
[CT] and surgical approaches) were reviewed, and a simulation experiment using a
head phantom was conducted using the same settings applied intraoperatively.
RESULTS: A 36-year-old man was referred after failure to locate a broken 31-G
dental needle. Computed tomography revealed migration of the needle into the
parapharyngeal space. Intraoperative X-ray fluoroscopy failed to identify the
needle, so a steel wire was applied as a reference during X-ray to locate the
foreign body. The needle was successfully removed using an intraoral approach
with tonsillectomy under surgical microscopy. The simulation showed that the
dental needle was able to be identified only after applying an appropriate
compensating filter, contrasting with the steel wire. CONCLUSION: Meticulous
preoperative simulation regarding visual identification of dental needle foreign
bodies is mandatory. Intraoperative radiography and an intraoral approach with
tonsillectomy under surgical microscopy offer benefits for accessing the
parapharyngeal space, specifically for cases medial to the great vessels.
PMID- 25139136
TI - Exploring the implementation of a medication adherence programme by community
pharmacists: a qualitative study.
AB - BACKGROUND: Medication adherence has been identified as an important factor for
clinical success. Twenty-four Swiss community pharmacists participated in the
implementation of an adherence support programme for patients with hypertension,
diabetes mellitus and/or dyslipidemia. The programme combined tailored
consultations with patients about medication taking (expected at an average of
one intervention per month) and the delivery of each drug in an electronic
monitoring system (MEMS6TM). OBJECTIVE: To explore pharmacists' perceptions and
experiences with implementation of the medication adherence programme and to
clarify why only seven patients were enrolled in total. SETTING: Community
pharmacies in French-speaking Switzerland. METHOD: Individual in-depth interviews
were audio-recorded, with 20 of the pharmacists who participated in the adherence
programme. These were transcribed verbatim, coded and thematically analysed.
Process quality was ensured by using an audit trail detailing the development of
codes and themes; furthermore, each step in the coding and analysis was verified
by a second, experienced qualitative researcher. MAIN OUTCOME MEASURE: Community
pharmacists' experiences and perceptions of the determining factors influencing
the implementation of the adherence programme. RESULTS: Four major barriers were
identified: (1) poor communication with patients resulting in insufficient
promotion of the programme; (2) insufficient collaboration with physicians; (3)
difficulty in integrating the programme into pharmacy organisation; and (4)
insufficient pharmacist motivation. This was related to the remuneration
perceived as insufficient and to the absence of clear strategic thinking about
the pharmacist position in the health care system. One major facilitator of the
programme's implementation was pre-existing collaboration with physicians.
CONCLUSION: A wide range of barriers was identified. The implementation of
medication adherence programmes in Swiss community pharmacies would benefit from
an extended training aimed at developing communication and change management
skills. Individualised onsite support addressing relevant barriers would also be
necessary throughout the implementation process.
PMID- 25139137
TI - Barriers to the implementation of advanced clinical pharmacy services at
Portuguese hospitals.
AB - BACKGROUND: In some countries, such as Portugal, clinical pharmacy services in
the hospital setting may be implemented to a lower extent than desirable. Several
studies have analysed the perceived barriers to pharmacy service implementation
in community pharmacy. OBJECTIVE: To identify the barriers towards the
implementation of advanced clinical pharmacy services at a hospital level in
Portugal, using medication follow-up as an example. SETTING: Hospital pharmacies
in Portugal. METHODS: A qualitative study based on 20 face-to-face semi
structured interviews of strategists and hospital pharmacists. The interview
guide was based on two theoretical frameworks, the Borum's theory of
organisational change and the Social Network Theory, and then adapted for the
Portuguese reality and hospital environments. A constant comparison process with
previously analysed interviews, using an inductive approach, was carried out to
allow themes to emerge. Themes were organised following the Leavitt's
Organizational Model: functions and objectives; hospital pharmacist; structure of
pharmacy services; environment; technology; and medication follow-up based on the
study topic. MAIN OUTCOME MEASURE: Barriers towards practice change. RESULTS:
Medication follow-up appeared not to be a well-known service in Portuguese
hospital pharmacies. The major barriers at the pharmacist level were their mind
set, resistance to change, and lack of readiness. Lack of time, excessive
bureaucratic and administrative workload, reduced workforce, and lack of support
from the head of the service and other colleagues were identified as structural
barriers. Lack of access to patients' clinical records and cumbersome procedures
to implement medication follow-up were recognised as technological barriers. Poor
communication with other healthcare professionals, and lack of support from
professional associations were the major environmental barriers. CONCLUSION: Few
of the barriers identified by Portuguese hospital pharmacists were consistent
with previous reports from community pharmacy. The mind-set of pharmacists and
predetermined attitudes are recognised as barriers that can give rise to new
perceived barriers.
PMID- 25139138
TI - Reply: To PMID 23535238.
PMID- 25139139
TI - Thyroid screening in pregnancy.
AB - The adverse impact of overt hypothyroidism that complicates pregnancy outcomes is
well-established and not debated. For more than a decade, however,
endocrinologists and obstetricians have been debating whether screening for
subclinical thyroid disorders during pregnancy should be routine or should
continue to be based on symptoms and risk factors. Several observational studies
have suggested that offspring of women with asymptomatic thyroid dysfunction were
at increased risk for impaired neurodevelopment. Other studies have suggested
that pregnant women with subclinical thyroid disease, particularly those
identified with an elevated thyroid-stimulating hormone (TSH) level may be at
increased risk for pregnancy complications such as fetal death, preterm birth, or
placental abruption. These data have prompted both obstetric and endocrinologic
professional societies to draft recommendations regarding screening for thyroid
disease during pregnancy, some of which are not entirely based on available
evidence. The prevalence of overt thyroid disease is estimated to be 1-2 per 1000
pregnancies and historically has not been considered high enough to justify
routine screening. Lower TSH thresholds (>2.5 mU/L) for the diagnosis of
hypothyroidism have been promoted, and women with subclinical thyroid dysfunction
commonly are included in estimates of thyroid disease during pregnancy, both of
which exaggerate prevalence rates. The most compelling recent evidence on this
issue has come from the Controlled Antenatal Thyroid Screening trial. After
almost 22,000 pregnant women were screened for either isolated high TSH or
isolated low free thyroxine level, 390 children of treated women with either
diagnosis were compared with 404 children of similar women who were not treated
during pregnancy. Treatment had no effect on mean offspring IQ at age 3 years or
the number of children with an IQ <85. Authors of this landmark study concluded
that antenatal screening and maternal treatment for women with subclinical
thyroid dysfunction did not result in improved cognitive function. An ongoing
intervention trial conducted by the Eunice Kennedy-Shriver National Institute of
Child Health and Human Development's Maternal-Fetal Medicine Units Network will
provide further clarity to this important question. In the interim, the debating
authors have concluded, after careful review of the currently published
literature, that routine screening for subclinical thyroid dysfunction during
pregnancy is not currently warranted at this time.
PMID- 25139140
TI - Impact of robotic operative efficiency on profitability.
PMID- 25139142
TI - In situ observation of model catalysts under reaction conditions using X-ray core
level spectroscopy.
AB - Chemical reactions at solid surfaces are of great importance in heterogeneous
catalysis and the understanding of their reaction mechanisms has been challenged
for a long time by a wide variety of approaches. In situ observation of model
catalysts under reaction conditions is a promising approach to understand the
mechanisms. Toward this aim we have been developing several spectroscopic
techniques using synchrotron-radiation X-rays. In this Personal Account,
synchrotron-radiation-based X-ray core-level spectroscopies for in situ
observation are introduced and some of their applications in studying the
mechanisms of catalytic reactions are highlighted. Future directions for further
development of these spectroscopies are also described.
PMID- 25139141
TI - Life in urban areas and breast cancer risk in the French E3N cohort.
AB - It has been suggested that women living in urban areas are at higher risk of
breast cancer (BC) compared to women living in rural areas. However, most
published studies on this topic are ecological and did not adjust for individual
BC risk factors. We investigated this hypothesis in a French prospective cohort.
Cox proportional hazards regression models were used to evaluate the association
between birth or residence in an urban area and BC risk among 75,889 women of the
French E3N cohort (aged 38-66 years at recruitment in 1990) before and after
adjustment for known BC risk factors and stratifying on birth cohort. From 1990
to 2008, a total of 5,145 BC cases were diagnosed. Being born in an urban area
was associated with BC risk before (HR 1.11, 95% CI 1.05-1.18) and after (HR
1.07, 95% CI 1.01-1.14) adjustment for known BC risk factors. Living in an urban
area in 1990 was not associated with BC risk. Being born in an urban area is
associated with a weak increase in BC risk. This may be suggestive of higher
exposure to air pollution and to other environmental exposures, to be
investigated in future studies.
PMID- 25139143
TI - Morphometric analysis and lymph node yield in laparoscopic complete mesocolic
excision performed by supervised trainees.
AB - BACKGROUND: Complete mesocolic excision with central vascular ligation (CME)
produces an optimal colonic cancer specimen. The ability of expert laparoscopic
surgeons to produce equivalent specimens is unknown. METHODS: Fresh specimen
photographs and clinicopathological data from patients undergoing
laparoscopically assisted CME at St Mark's Hospital, Harrow, were submitted for
independent pathological review. Surgery was performed by a mixture of consultant
specialists and trainees under consultant specialist supervision, between
February 2010 and July 2011. The planes of surgery were graded and tissue
morphometry was performed using standard methods. The results were compared with
published data from open CME and non-CME surgery. RESULTS: In total, 69 patients
were identified, and in 96 per cent resection was performed completely or
partially by surgical trainees. Laparoscopic CME produced a similar specimen to
open CME. The laparoscopic mesocolic plane resection rate was similar to that for
open surgery (90 versus 88 per cent). The distance between the bowel wall and
site of vascular division was similar for laparoscopic and open right-sided CME
(92 versus 95 mm respectively). The corresponding values for left-sided CME were
also similar (103 versus 107 mm). Compared with values from two non-CME series,
laparoscopic CME had a higher mesocolic plane rate (90 versus 40 and 48 per
cent), and resected more tissue between the bowel wall and the vascular division
(right-sided: 92 versus 72 and 76 mm; left-sided: 103 versus 85 and 70 mm). The
lymph node yield remained low following laparoscopic CME compared with open CME
(median 18 versus 32; P < 0.001) and identical to that of non-CME surgery (median
18). CONCLUSION: Laparoscopic CME can be performed to the same standard as open
surgery by supervised trainees. However, this did not increase the lymph node
yield.
PMID- 25139144
TI - Shear rate normalization is not essential for removing the dependency of flow
mediated dilation on baseline artery diameter: past research revisited.
AB - A ratio index (FMD%) is used ubiquitously to scale (by simple division) brachial
artery flow-mediated dilation (Ddiff) in direct proportion to baseline diameter
(Dbase). It is now known that Ddiff is inversely proportional to Dbase rendering
FMD% wholly inappropriate. Consequently, FMD% is still substantially dependent on
Dbase. Although this problem is grounded in statistics, normalization of FMD% for
the change in arterial shear rate (DeltaSR) has been proposed to remove this
Dbase-dependency. It was hypothesized that, if the flow-mediated response is
scaled properly to Dbase in the first place, shear rate normalization would not
be needed to remove Dbase-dependency. Dedicated software (Digitizelt) was
employed to extract the data from a seminal study on FMD% normalization. The
underlying allometric relationship between Dbase and peak diameter (Dpeak) was
described. The re-analyses revealed that the absolute change in arterial diameter
was strongly inversely proportional to Dbase (r= - 0.7, P < 0.0005). The
allometric exponent for the Dbase-Dpeak relationship was 0.82 (95% CI: 0.78-0.86)
rather than the value of 1 needed for appropriate use of FMD%. The allometric
approach completely eliminated the originally reported dependency on Dbase
without any need for DeltaSR normalization (r=0.0, P=0.96). The correlation
between DeltaSR and FMD% reduced from 0.69 to 0.37, when adjusted for Dbase. In
conclusion, this new re-analysis of data from an influential study demonstrates
that the FMD%-Dbase correlation is caused by the inappropriate size-scaling
properties of FMD% itself. Removal of Dbase-dependency via FMD%/DeltaSR
normalization is not essential at all if allometric scaling is applied to isolate
the flow-mediated response in the first place. Consequently, the influence of
DeltaSR on this properly scaled response can also be isolated and quantified
accurately without the confounding influence of Dbase.
PMID- 25139145
TI - Contribution of generative leisure activities to cognitive function in elderly
Sri Lankan adults.
AB - OBJECTIVES: To examine the unique contribution of generative leisure activities,
defined as activities motivated by a concern for others and a need to contribute
something to the next generation. DESIGN: Cross-sectional survey. SETTING: Peri
urban and rural area in southern Sri Lanka. PARTICIPANTS: Community-dwelling
adults aged 60 and older (N = 252). MEASUREMENTS: The main predictors were
leisure activities, grouped into generative, social, or solitary. The main
outcome was cognitive function, assessed using the Montreal Cognitive Assessment
(MoCA) and the Informant Questionnaire on Cognitive Decline in the Elderly
(IQCODE). RESULTS: More-frequent engagement in generative leisure activities was
associated with higher levels of cognitive function, independent of the effect of
other social and solitary leisure activities. In a fully adjusted model combining
all three leisure activities, generative activities independently predicted
cognitive function as measured using the MoCA (beta = 0.47, 95% confidence
interval (CI) = 0.11-0.83) and the IQCODE (beta = -0.81, 95% CI = -1.54 to
0.09). In this combined model, solitary activities were also independently
associated with slower cognitive decline using the MoCA (beta = 0.40, 95% CI =
0.16-0.64) but not the IQCODE (beta = -0.38, 95% CI = -0.88-0.12); the
association with social activities did not reach statistical significance with
either measure. These associations did not differ meaningfully according to sex.
CONCLUSION: Generative leisure activities are a promising area for the
development of interventions aimed at reducing cognitive decline in elderly
adults.
PMID- 25139146
TI - The patterns of health care utilization by elderly Europeans: frailty and its
implications for health systems.
AB - OBJECTIVE: To examine the patterns of health care utilization by the elderly and
test the influence of functional decline. DATA SOURCE AND STUDY DESIGN: We used
the three regular waves of the SHARE survey to estimate the influence of frailty
on health care utilization in 10 European countries. We controlled for the main
correlates of frailty and unobserved individual effects. RESULTS: The frail
elderly increase their primary and hospital care utilization before the onset of
disability. Multimorbidity moderates the effect of frailty on care utilization.
CONCLUSIONS: The prevalence of frailty is high in most countries and is expected
to increase. This renders frailty prevention and remediation efforts imperative
for two complementary reasons: to promote healthier aging and to reduce the
burden on health systems.
PMID- 25139147
TI - Antimicrobial light-activated materials: towards application for food and
environmental safety.
AB - AIMS: To produce light-activated antimicrobial materials composed of the
photodynamic dye phloxine B incorporated into paper or cellulose membranes and to
investigate ability of these materials to decrease bacterial loads on their
surfaces as well as on food surfaces that were in contact with these materials
under illumination with regular white light. METHODS AND RESULTS: Antimicrobial
cellulose-based materials with incorporated phloxine B were produced using a
layer-by-layer deposition method. Antimicrobial properties of the materials were
tested in model systems as well as for decontamination of food and food contact
surfaces. Pseudomonas aeruginosa, Listeria monocytogenes and Bacillus anthracis
were efficiently killed by exposure of the bacterial suspension to the dye
containing material under illumination with white light, but Salmonella
Typhimurium and Escherichia coli O157:H7 were only partially affected.
Application of the materials for decontamination of food surfaces artificially
contaminated with L. monocytogenes was shown to be ineffective, while the self
decontamination of the material surface by exposure to white light resulted in
eradication of L. monocytogenes cells from the material surface. CONCLUSIONS: The
developed materials showed significant self-decontaminating ability when under
illumination; however, decontamination of food surfaces in contact with the
developed materials was not achieved. SIGNIFICANCE AND IMPACT OF THE STUDY: The
study demonstrates the antibacterial activity of materials with incorporated
photodynamic dyes when under illumination with regular-intensity white light.
Possible uses of the light-activated antimicrobial materials for food processing,
as food contact surfaces, and surfaces in public areas to prevent cross
contamination are discussed.
PMID- 25139148
TI - Brain tumor cells in circulation are enriched for mesenchymal gene expression.
AB - Glioblastoma (GBM) is a highly aggressive brain cancer characterized by local
invasion and angiogenic recruitment, yet metastatic dissemination is extremely
rare. Here, we adapted a microfluidic device to deplete hematopoietic cells from
blood specimens of patients with GBM, uncovering evidence of circulating brain
tumor cells (CTC). Staining and scoring criteria for GBM CTCs were first
established using orthotopic patient-derived xenografts (PDX), and then applied
clinically: CTCs were identified in at least one blood specimen from 13 of 33
patients (39%; 26 of 87 samples). Single GBM CTCs isolated from both patients and
mouse PDX models demonstrated enrichment for mesenchymal over neural
differentiation markers compared with primary GBMs. Within primary GBMs, RNA in
situ hybridization identified a subpopulation of highly migratory mesenchymal
tumor cells, and in a rare patient with disseminated GBM, systemic lesions were
exclusively mesenchymal. Thus, a mesenchymal subset of GBM cells invades the
vasculature and may proliferate outside the brain. SIGNIFICANCE: GBMs are locally
invasive within the brain but rarely metastasize to distant organs, exemplifying
the debate over "seed" versus "soil." We demonstrate that GBMs shed CTCs with
invasive mesenchymal characteristics into the circulation. Rare metastatic GBM
lesions are primarily mesenchymal and show additional mutations absent in the
primary tumor.
PMID- 25139149
TI - Haematological and biochemical reference intervals for free-ranging brown bears
(Ursus arctos) in Sweden.
AB - BACKGROUND: Establishment of haematological and biochemical reference intervals
is important to assess health of animals on individual and population level.
Reference intervals for 13 haematological and 34 biochemical variables were
established based on 88 apparently healthy free-ranging brown bears (39 males and
49 females) in Sweden. The animals were chemically immobilised by darting from a
helicopter with a combination of medetomidine, tiletamine and zolazepam in April
and May 2006-2012 in the county of Dalarna, Sweden. Venous blood samples were
collected during anaesthesia for radio collaring and marking for ecological
studies. For each of the variables, the reference interval was described based on
the 95% confidence interval, and differences due to host characteristics sex and
age were included if detected. To our knowledge, this is the first report of
reference intervals for free-ranging brown bears in Sweden. RESULTS: The
following variables were not affected by host characteristics: red blood cell,
white blood cell, monocyte and platelet count, alanine transaminase, amylase,
bilirubin, free fatty acids, glucose, calcium, chloride, potassium, and cortisol.
Age differences were seen for the majority of the haematological variables,
whereas sex influenced only mean corpuscular haemoglobin concentration, aspartate
aminotransferase, lipase, lactate dehydrogenase, beta-globulin, bile acids,
triglycerides and sodium. CONCLUSIONS: The biochemical and haematological
reference intervals provided and the differences due to host factors age and
gender can be useful for evaluation of health status in free-ranging European
brown bears.
PMID- 25139153
TI - Dynamic changes in composition of extracts of natural products as monitored by in
situ NMR.
AB - The direct in situ NMR observation and quantification, based on the aldehyde -CH
chemical shift region, of the inter-conversion of secoiridoid derivatives due to
temperature and solvent effects is demonstrated in complex extracts of natural
products without prior isolation of the individual components. The equilibrium
between the aldehyde hydrate form and the dialdehyde form of the oleuropein
aglycon of an olive leaf aqueous extract in D(2)O was shown to be temperature
dependent. The resulting thermodynamic values of the Van't Hoff plot with
DeltaH(o) = -26.34 +/- 1.00 kJ mol(-1) and TDeltaS degrees (298 K) = -24.70 +/-
1.00 kJ mol(-1) demonstrate a significant entropy term which nearly compensates
the effect of enthalpy at room temperature. The equilibrium between the two
diastereomeric hemiacetal forms and the dialdehyde form of the oleuropein 6-O
beta-d-glucopyranoside aglycon of an olive leaf aqueous extract in CD(3) OD was
also shown to be strongly temperature dependent again because of the significant
entropy term (TDeltaS degrees (298 K) = -26.50 +/- 1.39 kJ mol(-1)) compared
with that of the enthalpy term (DeltaH(o) = -36.64 +/- 1.46 kJ mol(-1)). This is
the first demonstration of the significant role of the entropy parameter in
determining the equilibrium of chemical transformations in complex mixtures of
natural products due to solvent and temperature effects.
PMID- 25139151
TI - Evaluation of Hounsfield Units as a predictive factor for the outcome of
extracorporeal shock wave lithotripsy and stone composition.
AB - The objective of this study was to evaluate the utility of the Hounsfield Unit
(HU) values as a predictive factor of extracorporeal shock wave lithotripsy
outcome for ureteral and renal stones. We also assessed the possibility that HU
values could be used to predict stone composition. A retrospective study was
performed to measure stone HU values in 260 patients who underwent extracorporeal
shock wave lithotripsy (ESWL) for solitary renal and ureteral stones from July
2007 to January 2012. Stone volume, location, skin-to-stone distance, stone HU
values, and stone composition were assessed. Success of ESWL was defined as: (1)
being stone-free or (2) residual stone fragments <4 mm after 3 months by
radiography. Of the 260 assessed patients, 141 (54.2%) were stone-free, 32
(12.3%) had residual stone fragments <4 mm (clinically insignificant stone
fragments), and 87 (33.5%) had residual stone fragments >=4 mm after one round of
ESWL. Multivariate analysis revealed that stone location and mean HU were
significant predictors of ESWL success. Receiver operating characteristic curves
defined cutoff values for predicting treatment outcome. Treatment success rates
were significantly higher for stones <815 HU than with stones >815 HU (P <
0.0265). HU of calcium oxalate and calcium phosphate stones were higher than
those of uric acid stones, but we could not differentiate between calcium oxalate
monohydrate and calcium oxalate dihydrate stones. Evaluation of stone HU values
prior to ESWL can predict treatment outcome and aid in the development of
treatment strategies.
PMID- 25139150
TI - Comparative evaluation of efficacy of use of naftopidil and/or celecoxib for
medical treatment of distal ureteral stones.
AB - We performed a randomized, prospective study to assess the possible role of
combined a1D-receptor antagonist naftopidil and nonsteroidal anti-inflammatory
hormones celecoxib for the spontaneous expulsion of distal ureteral stones.
Patients were randomized to one of the three treatment groups. Treatment group 1
patients received naftopidil 50 mg/day, group 2 patients received naftopidil 50
mg/day plus celecoxib 200 mg (Take two capsules (400 mg) by mouth immediately,
then take one capsule (200 mg) by mouth every 12 h), and group 3 patients
received celecoxib 200 mg (Take two capsules (400 mg) by mouth immediately, then
take one capsule (200 mg) by mouth every 12 h). All patients were instructed to
drink at least 2 L of fluids daily. Pain descriptions were recorded by the
patients using the visual analog scale. All patients were followed up for 2
weeks. A total of 105 patients provided consent and 103 patients completed the
study. Stone expulsion was observed in 29 patients in group 1 (29 of 35, 82.86
%), 33 patients in group 2 (33 of 35, 94.29 %) and 20 patients in group 3 (20 of
33, 60.61 %). A statistically significant difference was noted with Chi-square
testing for stone expulsion rate between groups 1 and 3, and groups 2 and 3 (P =
0.04 and P = 0.000, respectively). Kaplan-Meier curves were plotted to access the
expulsion rate of each group over time. A significant difference was shown for
the expulsion rate between the group 3 and the other two groups. (P < 0.001 by
log-rank test).Average time to expulsion for groups 1, 2 and 3 was 8.00 +/- 2.07,
7.70 +/- 2.34 and 10.65 +/- 2.92 days, respectively (P = 0.000). Treatment with
naftopidil and celecoxib appears to be beneficial in distal ureter stone
clearance, shortened the expulsion time, and could be used reliably and
successfully to reduce the frequency and intensity of the pain episodes
particularly.
PMID- 25139154
TI - High-performance photoelectrochemical cells based on a binuclear ruthenium
catalyst for visible-light-driven water oxidation.
AB - Two photoanodes based on a binuclear (2) and a mononuclear ruthenium (3) water
oxidation catalysts were assembled in combination with a molecular
photosensitizer (1) by using a co-adsorption method. The anodes were used in dye
sensitized photoelectrochemical cells (DS-PECs) for visible-light-driven water
splitting. A DS-PEC device using TiO2 (1+2) as working electrode (WE) exhibits
better performance than TiO2 (1+3) as WE in light-driven water splitting.
Detailed photoelectrochemical studies on these DS-PEC devices are discussed.
PMID- 25139156
TI - A call to wellness - Whitiwhitia i te ora: exploring Maori and occupational
therapy perspectives on health.
AB - The World Health Organization records that indigenous peoples throughout the
world experience poor health. The concept of health was explored from a Maori
world view and compared with occupational therapy perspectives. The aim was to
understand and value indigenous knowledge and promote culturally safe responsive
practice. Maori methodologies were employed to protect the Maori knowledge shared
in the study. This involved applying seven principles, including respect for
people, be cautious, and look, listen, and speak. Perspectives on health and
wellbeing were collected in 2008-2009 from indigenous occupational therapists,
other occupational therapists and indigenous health practitioners using
interviews and a questionnaire. The findings are presented as a conceptual
framework, depicting a whare, a Maori meeting house to show relationships between
culture and health. Key concepts held by occupational therapists and Maori were
spirituality, holistic views, client responsive practice, and environmental
contexts. Areas of difference were the focus on occupations, the interdependence
of indigenous relationships, and the place of the extended family in supporting
wellness. A strength was the respect for Maori methodologies and limitations were
the number of participants (N = 23) and the small proportion of Maori therapists
in Aotearoa/New Zealand. RECOMMENDATIONS: Attention to culture is vital for
appropriate, safe, and responsive practice. The conceptual framework provides a
tool to inform, guide, and evaluate practice understandings. It acknowledges the
importance of the individual within their extended family, their natural
environment, and the historical, social, and political realities of living as
Maori. Further research should explore the use of the framework and interaction
between occupational therapy practice and specific indigenous cultures.
PMID- 25139157
TI - A simple thoracoscopic plication technique for diaphragmatic eventration in
neonates and infants: technical details and initial results.
AB - PURPOSE: Existing minimal-access surgical approaches for correction of
symptomatic diaphragmatic eventration may be technically difficult in neonates
and infants. We report technical details and initial outcomes of a novel, simple
thoracoscopic repair technique. METHODS: The technique uses one 3-mm camera port,
a 3-mm instrument incision without a port, and an 18-gauge spinal needle, which
is passed through the chest wall into the pleural space. The excess diaphragm is
first plicated over the needle, after which a non-absorbable suture is passed
through the needle and tied extracorporeally. The needle is passed repeatedly
until the desired degree of tension is achieved. A retrospective review was
performed for all patients undergoing repair by this technique. RESULTS: Nine
patients have undergone thoracoscopic plication at a median age of 3 months
(range 0.2-13.2 mos.) and a median weight of 4.5 kg (range 2.3-8.2 kg). No organ
injuries or conversions to thoracotomy occurred. Median operative time was 60
min. Patients repaired beyond the neonatal period were extubated in the operating
room. There were two post-operative pneumothoraces. No recurrences have been seen
at a mean follow-up of 17 months. CONCLUSION: This technique of thoracoscopic
diaphragm plication is safe, effective, and technically straightforward in
neonates and infants.
PMID- 25139155
TI - Muscle ectopic fat deposition contributes to anabolic resistance in obese
sarcopenic old rats through eIF2alpha activation.
AB - Obesity and aging are characterized by decreased insulin sensitivity (IS) and
muscle protein synthesis. Intramuscular ceramide accumulation has been implicated
in insulin resistance during obesity. We aimed to measure IS, muscle ceramide
level, protein synthesis, and activation of intracellular signaling pathways
involved in translation initiation in male Wistar young (YR, 6-month) and old
(OR, 25-month) rats receiving a low- (LFD) or a high-fat diet (HFD) for 10 weeks.
A corresponding cellular approach using C2C12 myotubes treated with palmitate to
induce intracellular ceramide deposition was taken. A decreased ability of
adipose tissue to store lipids together with a reduced adipocyte diameter and a
development of fibrosis were observed in OR after the HFD. Consequently, OR fed
the HFD were insulin resistant, showed a strong increase in intramuscular
ceramide level and a decrease in muscle protein synthesis associated with
increased eIF2alpha phosphorylation. The accumulation of intramuscular lipids
placed a lipid burden on mitochondria and created a disconnect between metabolic
and regulating pathways in skeletal muscles of OR. In C2C12 cells, palmitate
induced ceramide accumulation was associated with a decreased protein synthesis
together with upregulated eIF2alpha phosphorylation. In conclusion, a reduced
ability to expand adipose tissues was found in OR, reflecting a lower lipid
buffering capacity. Muscle mitochondrial activity was affected in OR conferring a
reduced ability to oxidize fatty acids entering the muscle cell. Hence, OR were
more prone to ectopic muscle lipid accumulation than YR, leading to decreased
muscle protein anabolism. This metabolic change is a potential therapeutic target
to counter sarcopenic obesity.
PMID- 25139158
TI - Esophagogastric dissociation reduces the re-operation rate for persistent
gastroesophageal reflux in severely neurologically impaired children.
AB - PURPOSE: In this study we want to demonstrate the effectiveness of the
esophagogastric dissociation as a first level operation in treatment of the
gastroesophageal reflux in severe neurologically impaired children, in term of a
reduction of reoperation rate. METHODS: We divided patients operated from 1998 to
2005 in a group A, composed by children treated with fundoplication, and in a
group AR, composed by the patients of group A who had a recurrence of reflux and
that was treated with esophagogastric dissociation. Patients operated from 2005
to 2013 were selected on the basis of the severity of the neurological impairment
and were divided in a group B, treated with fundoplication, and in a group C of
more severe impaired children, treated with esophagogastric dissociation. Data
regarding the complications of the A and C groups were analyzed with Fisher's
test. RESULTS: We evaluated 63 patients: 34 (54%) in group A, 11 in group AR, 15
(23.6%) in group B, 14 (22.4%) in group C. The Fisher's test showed a non
significant difference with a p value of 0.2. CONCLUSION: Despite of statistic
result we believe that TOGD is a useful procedure as the first choice of surgical
management in severe neurological impaired children affected by gastroesophageal
reflux.
PMID- 25139159
TI - A secreted protein with plant-specific cysteine-rich motif functions as a mannose
binding lectin that exhibits antifungal activity.
AB - Plants have a variety of mechanisms for defending against plant pathogens and
tolerating environmental stresses such as drought and high salinity. Ginkbilobin2
(Gnk2) is a seed storage protein in gymnosperm that possesses antifungal activity
and a plant-specific cysteine-rich motif (domain of unknown function26 [DUF26]).
The Gnk2-homologous sequence is also observed in an extracellular region of
cysteine-rich repeat receptor-like kinases that function in response to biotic
and abiotic stresses. Here, we report the lectin-like molecular function of Gnk2
and the structural basis of its monosaccharide recognition. Nuclear magnetic
resonance experiments showed that mannan was the only yeast (Saccharomyces
cerevisiae) cell wall polysaccharide that interacted with Gnk2. Gnk2 also
interacted with mannose, a building block of mannan, with a specificity that was
similar to those of mannose-binding legume lectins, by strictly recognizing the
configuration of the hydroxy group at the C4 position of the monosaccharide. The
crystal structure of Gnk2 in complex with mannose revealed that three residues
(asparagine-11, arginine-93, and glutamate-104) recognized mannose by hydrogen
bonds, which defined the carbohydrate-binding specificity. These interactions
were directly related to the ability of Gnk2 to inhibit the growth of fungi,
including the plant pathogenic Fusarium spp., which were disrupted by mutation of
arginine-93 or the presence of yeast mannan in the assay system. In addition,
Gnk2 did not inhibit the growth of a yeast mutant strain lacking the alpha1,2
linked mannose moiety. These results provide insights into the molecular basis of
the DUF26 protein family.
PMID- 25139160
TI - Increased ratio of electron transport to net assimilation rate supports elevated
isoprenoid emission rate in eucalypts under drought.
AB - Plants undergoing heat and low-CO2 stresses emit large amounts of volatile
isoprenoids compared with those in stress-free conditions. One hypothesis posits
that the balance between reducing power availability and its use in carbon
assimilation determines constitutive isoprenoid emission rates in plants and
potentially even their maximum emission capacity under brief periods of stress.
To test this, we used abiotic stresses to manipulate the availability of reducing
power. Specifically, we examined the effects of mild to severe drought on
photosynthetic electron transport rate (ETR) and net carbon assimilation rate
(NAR) and the relationship between estimated energy pools and constitutive
volatile isoprenoid emission rates in two species of eucalypts: Eucalyptus
occidentalis (drought tolerant) and Eucalyptus camaldulensis (drought sensitive).
Isoprenoid emission rates were insensitive to mild drought, and the rates
increased when the decline in NAR reached a certain species-specific threshold.
ETR was sustained under drought and the ETR-NAR ratio increased, driving
constitutive isoprenoid emission until severe drought caused carbon limitation of
the methylerythritol phosphate pathway. The estimated residual reducing power
unused for carbon assimilation, based on the energetic status model,
significantly correlated with constitutive isoprenoid emission rates across
gradients of drought (r(2) > 0.8) and photorespiratory stress (r(2) > 0.9).
Carbon availability could critically limit emission rates under severe drought
and photorespiratory stresses. Under most instances of moderate abiotic stress
levels, increased isoprenoid emission rates compete with photorespiration for the
residual reducing power not invested in carbon assimilation. A similar mechanism
also explains the individual positive effects of low-CO2, heat, and drought
stresses on isoprenoid emission.
PMID- 25139161
TI - Increased GDF9 and BMP15 mRNA levels in cumulus granulosa cells correlate with
oocyte maturation, fertilization, and embryo quality in humans.
AB - BACKGROUND: Oocyte secreted factors (OSFs), including growth differentiation
factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), play an important role
in the process of follicular development and oocyte maturation. Since OSFs are
expressed in oocytes and cumulus granulosa cells, the aim of the present study
was to explore whether the expression levels of GDF9 and BMP15 mRNAs in cumulus
granulosa cells can be used as molecular markers for predicting oocyte
developmental potential. METHODS: Cumulus cells of 2426 cumulus-oocyte complexes
were collected from 196 female patients who underwent intracytoplasmic sperm
injection (ICSI) and were used for mRNA detection on the egg retrieval day.
Pearson correlation analysis was used to analyze the correlation between OSF
expression and general physiological parameters. Partial correlation analysis was
used to analyze the correlation between OSF expression and oocyte developmental
potential. Covariance analysis was used to compare OSF expression among different
groups. Receiver operating characteristic curves were used to examine the
diagnostic value of GDF9 and BMP15 mRNA for predicting pregnancy. RESULTS: The
expression levels of GDF9 and BMP15 mRNAs were significantly associated with age,
body mass index (BMI), oocyte maturation, normal fertilization, and cleavage rate
(P < 0.05). The expression levels of GDF9 and BMP15 mRNAs in the group with high
quality embryos were significantly higher than those in the group without high
quality embryos (P < 0.05). The expression levels of GDF9 and BMP15 mRNAs in the
pregnancy group were significantly higher than those in the nonpregnancy group (P
< 0.05). The cut-off value of GDF9 mRNA for predicting pregnancy was 4.82, with a
sensitivity of 82% and a specificity of 64%. The cut-off value of BMP15 mRNA for
predicting pregnancy was 2.60, with a sensitivity of 78% and a specificity of
52%. CONCLUSIONS: The expression levels of GDF9 and BMP15 mRNAs were closely
associated with oocyte maturation, fertilization, embryo quality, and pregnancy
outcome; therefore, GDF9 and BMP15 mRNAs in cumulus granulosa cells may be
considered as new molecular markers for predicting oocyte developmental
potential.
PMID- 25139162
TI - Clinical symptoms predict poor overall survival in chronic-dialysis patients with
renal cell carcinoma associated with end-stage renal disease.
AB - OBJECTIVE: To evaluate which clinical symptoms predict the survival of patients
with renal cell carcinoma associated with end-stage renal disease under chronic
dialysis. METHODS: We retrospectively evaluated 401 patients with renal cell
carcinoma associated with end-stage renal disease who underwent radical
nephrectomy at our institute up through December 2012. Patients were divided into
two groups: the symptomatic group and the incidental group, by diagnosis. We
compared the clinicopathologic features and patient survival of the two groups
and investigated prognostic factors using Cox multivariate analysis. RESULTS: Of
the 401 patients, 124 (30.9%) were in the symptomatic group and 277 (69.0%) in
the incidental group. The symptomatic group included more advanced tumors in
terms of larger tumor size, higher stage and higher grade compared with the
incidental group. The 5-year cancer-specific survival and overall survival of the
symptomatic and incidental groups were 76.9 vs. 95.3% (P < 0.001) and 64.2 vs.
84.9% (P < 0.001), respectively. On multivariate analysis, the presence of
symptoms, higher age, higher stage, diabetic nephropathy and longer hemodialysis
duration were independent prognostic factors. CONCLUSIONS: Symptomatic detection
was significantly associated with worse overall survival in patients with renal
cell carcinoma associated with end-stage renal disease as well as sporadic renal
cell carcinoma. The high incidence of renal cell carcinoma as well as the poor
oncologic outcome in patients with longer dialysis therapy may suggest an
important role for routine screening in these patients.
PMID- 25139163
TI - Construction of predictive models for cancer-specific survival of patients with
non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin: results
from a multicenter retrospective study.
AB - OBJECTIVE: The aims of this study were to clarify the prognostic factors and to
validate the bacillus Calmette-Guerin failure classification advocated by Nieder
et al. in patients with non-muscle-invasive bladder cancer who had intravesical
recurrence after bacillus Calmette-Guerin therapy. METHODS: Data from 402
patients who received intravesical bacillus Calmette-Guerin therapy between
January 1990 and November 2011 were collected from 10 institutes. Among these
patients, 187 with bacillus Calmette-Guerin failure were analyzed for this study.
RESULTS: Twenty-nine patients (15.5%) were diagnosed with progression at the
first recurrence after bacillus Calmette-Guerin therapy. Eighteen (62.1%) of them
died of bladder cancer. A total of 158 patients were diagnosed with non-muscle
invasive bladder cancer at the first recurrence after bacillus Calmette-Guerin
therapy. Of them, 23 (14.6%) underwent radical cystectomy. No patients who
underwent radical cystectomy died of bladder cancer during the follow-up. On
multivariate analysis of the 135 patients with bladder preservation, the
independent prognostic factors for cancer-specific survival were age (>=70 [P =
0.002]), tumor size (>=3 cm [P = 0.015]) and the Nieder classification (bacillus
Calmette-Guerin refractory [P < 0.001]). In a subgroup analysis, the estimated 5
year cancer-specific survival rates in the groups with no positive, one positive
and two to three positive factors were 100, 93.4 and 56.8%, respectively (P <
0.001). CONCLUSIONS: Patients with stage progression at the first recurrence
after bacillus Calmette-Guerin therapy had poor prognoses. Three prognostic
factors for predicting survival were identified and used to categorize patients
with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin
into three risk groups based on the number of prognostic factors in each one.
PMID- 25139164
TI - Barriers to cervical cancer screening and follow-up care among Black Women in
Massachusetts.
AB - OBJECTIVE: To explore factors that might lead to delays in appropriate cervical
cancer screening and diagnosis among Black women in Massachusetts. DESIGN:
Qualitative using focus groups. SETTING: Hospitals, health centers, and community
based organizations in Boston, Massachusetts. PARTICIPANTS: Sixty-four
participants including Black, non-Hispanic women from the general population and
cervical cancer survivors, community leaders in women's health, and health care
providers. METHODS: Six focus groups. Data were analyzed using methods based on
grounded theory. RESULTS: Findings from interviews revealed that inadequate
information and education of providers and patients create barriers to
appropriate screening and treatment practices for Black women. Fear, cultural
beliefs, and compounding factors related to poverty, gender roles, and health
system barriers create delays to screening and follow-up care. Also, unconscious
bias, therapeutic delays, and miscommunication are important factors affecting
continuity of care. CONCLUSION: These results suggest a need for comprehensive,
culturally specific cervical cancer prevention education initiatives and
interventions for Black women and strategies to improve patient-provider
relationships.
PMID- 25139166
TI - Mean sojourn time of preclinical gastric cancer in Korean men: a retrospective
observational study.
AB - OBJECTIVES: This retrospective cohort study aimed to estimate the mean sojourn
time (MST) of preclinical gastric cancer in Korean men. METHODS: The subjects
consisted of voluntary male screenees aged 40 to 69 years who underwent
subsequent screening gastroscopies after testing negative at a baseline screening
performed between January 2007 and December 2011. A new case was defined if
gastric cancer cells were present in the biopsy specimens obtained from
gastroscopy. The follow-up period was calculated as the number of person-years
between the date of baseline screening gastroscopy and positive findings at a
subsequent screening. The MST was calculated using transition rates of gastric
cancer to determine the best screening interval. RESULTS: Of the 171 979
voluntary male screenees, 61 688 (36%) underwent subsequent screening
gastroscopies between January 2007 and December 2011. A total of 91 incident
cases were found during 19 598 598 person-years of follow-up. The MST of gastric
cancer was 2.37 years (95% confidence intervals, 1.92 to 2.96), and those aged 40
to 49 years had a shorter MST than those 50 to 69 years did. CONCLUSIONS: These
findings support the 2-year interval of screening recommended by the nationwide
gastric cancer screening program in Korea. Further studies for the age-specific
MST among women are needed. OBJECTIVES: This retrospective cohort study aimed to
estimate the mean sojourn time (MST) of preclinical gastric cancer in Korean men.
METHODS: The subjects consisted of voluntary male screenees aged 40 to 69 years
who underwent subsequent screening gastroscopies after testing negative at a
baseline screening performed between January 2007 and December 2011. A new case
was defined if gastric cancer cells were present in the biopsy specimens obtained
from gastroscopy. The follow-up period was calculated as the number of person
years between the date of baseline screening gastroscopy and positive findings at
a subsequent screening. The MST was calculated using transition rates of gastric
cancer to determine the best screening interval. RESULTS: Of the 171 979
voluntary male screenees, 61 688 (36%) underwent subsequent screening
gastroscopies between January 2007 and December 2011. A total of 91 incident
cases were found during 19 598 598 person-years of follow-up. The MST of gastric
cancer was 2.37 years (95% confidence intervals, 1.92 to 2.96), and those aged 40
to 49 years had a shorter MST than those 50 to 69 years did. CONCLUSIONS: These
findings support the 2-year interval of screening recommended by the nationwide
gastric cancer screening program in Korea. Further studies for the age-specific
MST among women are needed.
PMID- 25139165
TI - Cancer control programs in East Asia: evidence from the international literature.
AB - Cancer is a major cause of mortality and morbidity throughout the world,
including the countries of North-East and South-East Asia. Assessment of burden
through cancer registration, determination of risk and protective factors, early
detection and screening, clinical practice, interventions for example in
vaccination, tobacco cessation efforts and palliative care all should be included
in comprehensive cancer control programs. The degree to which this is possible
naturally depends on the resources available at local, national and international
levels. The present review concerns elements of cancer control programs
established in China, Taiwan, Korea, and Japan in North-East Asia, Viet Nam,
Thailand, Malaysia, and Indonesia as representative larger countries of South
East Asia for comparison, using the published literature as a guide. While major
advances have been made, there are still areas which need more attention,
especially in South-East Asia, and international cooperation is essential if
standard guidelines are to be generated to allow effective cancer control efforts
throughout the Far East.
PMID- 25139167
TI - Variations in the hospital standardized mortality ratios in Korea.
AB - OBJECTIVES: The hospital standardized mortality ratio (HSMR) has been widely used
because it allows for robust risk adjustment using administrative data and is
important for improving the quality of patient care. METHODS: All inpatients
discharged from hospitals with more than 700 beds (66 hospitals) in 2008 were
eligible for inclusion. Using the claims data, 29 most responsible diagnosis
(MRDx), accounting for 80% of all inpatient deaths among these hospitals, were
identified, and inpatients with those MRDx were selected. The final study
population included 703 571 inpatients including 27 718 (3.9% of all inpatients)
in-hospital deaths. Using logistic regression, risk-adjusted models for
predicting in-hospital mortality were created for each MRDx. The HSMR of
individual hospitals was calculated for each MRDx using the model coefficients.
The models included age, gender, income level, urgency of admission, diagnosis
codes, disease-specific risk factors, and comorbidities. The Elixhauser
comorbidity index was used to adjust for comorbidities. RESULTS: For 26 out of 29
MRDx, the c-statistics of these mortality prediction models were higher than 0.8
indicating excellent discriminative power. The HSMR greatly varied across
hospitals and disease groups. The academic status of the hospital was the only
factor significantly associated with the HSMR. CONCLUSIONS: We found a large
variation in HSMR among hospitals; therefore, efforts to reduce these variations
including continuous monitoring and regular disclosure of the HSMR are required.
OBJECTIVES: The hospital standardized mortality ratio (HSMR) has been widely used
because it allows for robust risk adjustment using administrative data and is
important for improving the quality of patient care. METHODS: All inpatients
discharged from hospitals with more than 700 beds (66 hospitals) in 2008 were
eligible for inclusion. Using the claims data, 29 most responsible diagnosis
(MRDx), accounting for 80% of all inpatient deaths among these hospitals, were
identified, and inpatients with those MRDx were selected. The final study
population included 703 571 inpatients including 27 718 (3.9% of all inpatients)
in-hospital deaths. Using logistic regression, risk-adjusted models for
predicting in-hospital mortality were created for each MRDx. The HSMR of
individual hospitals was calculated for each MRDx using the model coefficients.
The models included age, gender, income level, urgency of admission, diagnosis
codes, disease-specific risk factors, and comorbidities. The Elixhauser
comorbidity index was used to adjust for comorbidities. RESULTS: For 26 out of 29
MRDx, the c-statistics of these mortality prediction models were higher than 0.8
indicating excellent discriminative power. The HSMR greatly varied across
hospitals and disease groups. The academic status of the hospital was the only
factor significantly associated with the HSMR. CONCLUSIONS: We found a large
variation in HSMR among hospitals; therefore, efforts to reduce these variations
including continuous monitoring and regular disclosure of the HSMR are required.
PMID- 25139169
TI - Analysis of the change of health status among the republic of Korea air force
soldiers during military service.
AB - OBJECTIVES: The aim of this study was to investigate whether the health status of
Republic of Korea Air Force (ROKAF) soldiers changed after one year of military
service. METHODS: We selected 483 ROKAF soldiers from the 11 749 recruits who
participated in the 2011 physical examination. The selected soldiers underwent
another physical examination in 2012 for advancement to senior airman. Data from
2011 and 2012 were merged. To collect data on lifestyle, a questionnaire was sent
to all included subjects via the military intranet e-mail service. RESULTS: The
percentage of recruits with an abnormal alanine transaminase level (normal range
<40 IU/L) decreased from recruitment (13.7%) to the following year (2.7%).
Moreover, the percentage of obese soldiers (body mass index >=25 kg/m(2))
decreased from recruitment (20.5%) to the following year (10.4%). There was a
significant change in mean duration of exercise carried out each day before
(0.8+/-1.3 hours) and after (1.0+/-0.7 hours) joining the ROKAF service.
CONCLUSIONS: These ROKAF soldiers were generally in good health before and after
joining the armed service. After one year of military service, the health status
of most soldiers improved, especially with respect to body mass index and alanine
transaminase level. OBJECTIVES: The aim of this study was to investigate whether
the health status of Republic of Korea Air Force (ROKAF) soldiers changed after
one year of military service. METHODS: We selected 483 ROKAF soldiers from the 11
749 recruits who participated in the 2011 physical examination. The selected
soldiers underwent another physical examination in 2012 for advancement to senior
airman. Data from 2011 and 2012 were merged. To collect data on lifestyle, a
questionnaire was sent to all included subjects via the military intranet e-mail
service. RESULTS: The percentage of recruits with an abnormal alanine
transaminase level (normal range <40 IU/L) decreased from recruitment (13.7%) to
the following year (2.7%). Moreover, the percentage of obese soldiers (body mass
index >=25 kg/m2) decreased from recruitment (20.5%) to the following year
(10.4%). There was a significant change in mean duration of exercise carried out
each day before (0.8+/-1.3 hours) and after (1.0+/-0.7 hours) joining the ROKAF
service. CONCLUSIONS: These ROKAF soldiers were generally in good health before
and after joining the armed service. After one year of military service, the
health status of most soldiers improved, especially with respect to body mass
index and alanine transaminase level.
PMID- 25139168
TI - The prevalence of cardiovascular disease risk factors and the Framingham Risk
Score in patients undergoing percutaneous intervention over the last 17 years by
gender: time-trend analysis from the Mayo Clinic PCI Registry.
AB - OBJECTIVES: This study aims to investigate trends of cardiovascular disease (CVD)
risk factor profiles over 17 years in percutaneous coronary intervention (PCI)
patients at the Mayo Clinic. METHODS: We performed a time-trend analysis within
the Mayo Clinic PCI Registry from 1994 to 2010. Results were the incidence and
prevalence of CVD risk factors as estimate by the Framingham risk score. RESULTS:
Between 1994 and 2010, 25 519 patients underwent a PCI. During the time assessed,
the mean age at PCI became older, but the gender distribution did not change. A
significant trend towards higher body mass index and more prevalent
hypercholesterolemia, hypertension, and diabetes was found over time. The
prevalence of current smokers remained unchanged. The prevalence of ever-smokers
decreased among males, but increased among females. However, overall CVD risk
according to the Framingham risk score (FRS) and 10-year CVD risk significantly
decreased. The use of most of medications elevated from 1994 to 2010, except for
beta-blockers and angiotensin converting enzyme inhibitors decreased after 2007
and 2006 in both baseline and discharge, respectively. CONCLUSIONS: Most of the
major risk factors improved and the FRS and 10-year CVD risk declined in this
population of PCI patients. However, obesity, history of hypercholesterolemia,
hypertension, diabetes, and medication use increased substantially. Improvements
to blood pressure and lipid profile management because of medication use may have
influenced the positive trends. OBJECTIVES: This study aims to investigate trends
of cardiovascular disease (CVD) risk factor profiles over 17 years in
percutaneous coronary intervention (PCI) patients at the Mayo Clinic. METHODS: We
performed a time-trend analysis within the Mayo Clinic PCI Registry from 1994 to
2010. Results were the incidence and prevalence of CVD risk factors as estimate
by the Framingham risk score. RESULTS: Between 1994 and 2010, 25 519 patients
underwent a PCI. During the time assessed, the mean age at PCI became older, but
the gender distribution did not change. A significant trend towards higher body
mass index and more prevalent hypercholesterolemia, hypertension, and diabetes
was found over time. The prevalence of current smokers remained unchanged. The
prevalence of ever-smokers decreased among males, but increased among females.
However, overall CVD risk according to the Framingham risk score (FRS) and 10
year CVD risk significantly decreased. The use of most of medications elevated
from 1994 to 2010, except for beta-blockers and angiotensin converting enzyme
inhibitors decreased after 2007 and 2006 in both baseline and discharge,
respectively. CONCLUSIONS: Most of the major risk factors improved and the FRS
and 10-year CVD risk declined in this population of PCI patients. However,
obesity, history of hypercholesterolemia, hypertension, diabetes, and medication
use increased substantially. Improvements to blood pressure and lipid profile
management because of medication use may have influenced the positive trends.
PMID- 25139170
TI - Older adults' perception of chronic illness management in South Korea.
AB - OBJECTIVES: Despite the recent emphasis on a patient-centered chronic care model,
few studies have investigated its use in older adults in South Korea. We explored
how older Korean adults perceive and cope with their chronic illness. METHODS: We
conducted focus group interviews in Seoul, Korea in January 2010. Focus groups
were formed by disease type (hypertension and type 2 diabetes) and gender using
purposive sampling. Inclusion criteria were patients aged 60 and over who had
been diagnosed with diabetes or hypertension and received care at a community
health center for at least six months prior to participation. Interview data were
analyzed through descriptive content analysis. RESULTS: Among personal factors,
most participants felt overwhelmed when they received their diagnosis. However,
with time and control of their acute symptoms using medication, their worry
diminished and participants tended to denying being identified as a patient or
sick person. Among socio-familial factors, participants reported experiencing
stigma with their chronic illness and feeling it was a symbol of weakness.
Instead of modifying their lifestyles, which might interfere with their social
relationships, they resorted to only following their medicine regime prescribed
by their doctor. Participants also reported feeling that their doctor only
prescribed medications and acted in an authoritative and threatening manner to
induce and reinforce participants' compliance with treatment. CONCLUSIONS: For
successful patient-centered management of chronic illnesses, supportive
environments that include family, friends, and healthcare providers should be
established. OBJECTIVES: Despite the recent emphasis on a patient-centered
chronic care model, few studies have investigated its use in older adults in
South Korea. We explored how older Korean adults perceive and cope with their
chronic illness. METHODS: We conducted focus group interviews in Seoul, Korea in
January 2010. Focus groups were formed by disease type (hypertension and type 2
diabetes) and gender using purposive sampling. Inclusion criteria were patients
aged 60 and over who had been diagnosed with diabetes or hypertension and
received care at a community health center for at least six months prior to
participation. Interview data were analyzed through descriptive content analysis.
RESULTS: Among personal factors, most participants felt overwhelmed when they
received their diagnosis. However, with time and control of their acute symptoms
using medication, their worry diminished and participants tended to denying being
identified as a patient or sick person. Among socio-familial factors,
participants reported experiencing stigma with their chronic illness and feeling
it was a symbol of weakness. Instead of modifying their lifestyles, which might
interfere with their social relationships, they resorted to only following their
medicine regime prescribed by their doctor. Participants also reported feeling
that their doctor only prescribed medications and acted in an authoritative and
threatening manner to induce and reinforce participants' compliance with
treatment. CONCLUSIONS: For successful patient-centered management of chronic
illnesses, supportive environments that include family, friends, and healthcare
providers should be established.
PMID- 25139171
TI - Effect of DOCA/salt hypertension on CRF expression in the amygdala and the
autonomic stress response in conscious rats.
AB - The effects of DOCA/salt treatment on amygdala-area CRF gene expression and the
autonomic response to air jet stress (AJS) were evaluated in conscious male
Sprague Dawley (SD) rats. Fifteen days of DOCA/salt treatment significantly
increased resting arterial pressure (AP), decreased resting heart rate (HR) and
significantly reduced regional CRF mRNA compared to controls (23+/-7% vs. 100+/
26%) independent of changes in regional CRF receptor expression. Twenty min of
AJS elicited a rise in AP (~15mmHg) that was similar in both DOCA/salt animals
(n=11) and controls (n=6). Alternatively, increases in HR were significantly
different in the DOCA/salt animals compared to controls; including one group of
DOCA/salt animals (n=5) which responded with an attenuated HR response at the
onset of AJS (low-responders) and a second group (n=6) which demonstrated an
elevated HR response to AJS (high-responders), specifically during the last 10min
of AJS. The divergent HR responses to AJS in the DOCA/salt animals were linked to
differences in resting heart rate variability. During recovery HR returned to
baseline within 10min in both control and the low responder DOCA group but
indicators of spontaneous baroreflex gain only increased significantly in
controls. HR in the high-responder DOCA animals did not return to baseline during
the same period. These results show that DOCA/salt treatment triggers
downregulation of CRF gene expression in the region of the amygdala and
significantly alters the HR response to acute stress but does not alter the
pressor response to stress compared to normotensive controls.
PMID- 25139172
TI - Potential application of non-flavonoid phenolics in diabetes: antiinflammatory
effects.
AB - Polyphenols are members of a very large family of plant-derived compounds that
may have beneficial effects on human health, and thus their study has become an
increasingly important area of human nutrition research. Considering that it is
increasingly accepted that chronic sub-acute inflammation plays an important role
in the development of insulin resistance and of diabetes in animals and in
humans, the aim of the present review is to compile information concerning the
anti-inflammatory effects of non-flavonoid polyphenols on diabetes prevention
and/or treatment. Most of these studies have been carried out with different
cultured cells and using animal models displaying different types of diabetes,
such as diabetes induced by streptozotocin or streptozotocin-nicotinamide,
genetic diabetes or diabetes induced by high-fat feeding. In general terms, non
flavonoid polyphenols reduce the production of inflammatory mediators, such as IL
1beta, IL-8, MCP-1, COX-2 or iNOS in these animal models of diabetes. This effect
is accompanied in the vast majority of these studies by improved insulin action.
In addition, some of the non-flavonoid polyphenols are also able to ameliorate or
prevent several pathological alterations associated with the development of
diabetes, such as nephropathy, cardiopathy or retinopathy. Very little
information has been reported with regard to human studies to date. Thus, new
studies are needed to confirm if the beneficial effects observed in preclinical
studies can apply to human beings.
PMID- 25139173
TI - Ulipristal acetate resembles mifepristone in modulating human fallopian tube
function.
AB - STUDY QUESTION: Do ulipristal acetate (UPA) and mifepristone have an effect on
ciliary beat frequency and muscular contractions in the human Fallopian tube?
SUMMARY ANSWER: UPA, in resemblance to mifepristone, inhibits ciliary beat and
muscular contraction of the human Fallopian tube, probably through an agonistic
effect on the tubal progesterone receptor. WHAT IS KNOWN ALREADY: UPA, like
mifepristone, acts as an emergency contraceptive mainly by inhibiting ovulation.
Little is known about its effects on tubal function. STUDY DESIGN, SIZE,
DURATION: This was an in vitro experimental study using Fallopian tube samples
collected from 11 women undergoing hysterectomy for benign non-tubal
gynaecological conditions. PARTICIPANTS/MATERIALS, SETTING, METHODS: The tubal
epithelium and longitudinal smooth muscle fibres were isolated, cultured and
treated with UPA at graded concentrations of 0, 20, 200 and 2000 ng/ml, and
mifepristone at graded concentrations of 0, 300, 3000 and 30 000 ng/ml,
respectively. After treatment, ciliary beat frequency was determined using a
photometric method. Basal tone, amplitude and frequency of muscular contraction
were recorded through a force transducer. The mRNA expression of progesterone
receptor (total and PR-B isoform), glycodelin and adrenomedullin were determined
by real-time quantitative PCR. MAIN RESULTS AND THE ROLE OF CHANCE: There was an
overall dose-dependent suppressive effect on ciliary beat frequency (P < 0.0001)
after treatment with UPA at all concentrations and with mifepristone at 3000
ng/ml or above. The basal tone, amplitude and frequency of muscular contractions
were significantly reduced (P < 0.05) after treatment with UPA at 200 ng/ml or
above, and with mifepristone at 3000 ng/ml or above. UPA treatment at 200 ng/ml
or above significantly up-regulated the mRNA expression of progesterone receptor
and glycodelin and down-regulated the mRNA expression of adrenomedullin in
Fallopian tube tissue (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: Whether or
not the tubal effect may translate into additional mechanisms for contraceptive
action in vivo is uncertain. WIDER IMPLICATIONS OF THE FINDINGS: The clinical
relevance of UPA with regard to contraceptive activity is worthy of further
exploration. STUDY FUNDING/COMPETING INTERESTS: The study was supported by a Seed
Fund from the Centre of Reproduction, Development and Growth, Faculty of
Medicine, the University of Hong Kong. All authors have no competing interest to
declare.
PMID- 25139176
TI - Fast synthesis of high-quality reduced graphene oxide at room temperature under
light exposure.
AB - An approach of presenting new reducing reagents, sodium-benzophenone (Na-B) or Na
B in the presence of the hydrazine (Na-B-H) system under light exposure could
produce rGOs with/without N-doping at room temperature in both the solution phase
and on a solid substrate. Benzophenone activated those solutions acting as a
photosensitizer under light. It was assumed that the newly generated radical
anions with electrons from Na-B under light can reduce GO to rGO sheets (rGONa
B1). In addition, the Na-B-H system can allow a higher degree of reduction with
the doping of nitrogen atoms by the introduction of hydrazine to produce radical
anions and electrons with a sodium hydrazide complex, which helps decrease the
sheet resistance of the as-made rGONa-B-H2. The excellent properties (very low
oxygen content (C/O ~16.2), and low sheet resistance (~130 Omega square(-1))) of
the rGOs were confirmed by XPS, XRD, IR, Raman spectroscopy, TGA, wettability,
and sheet resistance measurements. High-quality rGO films on flexible substrates
could be prepared by directly immersing the GO films in these solutions for
several minutes.
PMID- 25139174
TI - The effect of metformin treatment in vivo on acute and long-term energy
metabolism and progesterone production in vitro by granulosa cells from women
with polycystic ovary syndrome.
AB - STUDY QUESTION: What are the consequences of polycystic ovary syndrome (PCOS)
pathology and metformin-pretreatment in vivo in women with PCOS on the metabolism
and steroid production of follicular phenotype- and long-term cultured-granulosa
cells (GC)? SUMMARY ANSWER: PCOS pathology significantly compromised glucose
metabolism and the progesterone synthetic capacity of follicular- and long-term
cultured-GCs and the metabolic impact of PCOS on GC function was alleviated by
metformin-pretreatment in vivo. WHAT IS KNOWN ALREADY: Granulosa cells from women
with PCOS have been shown to have an impaired insulin-stimulated glucose uptake
and lactate production in vitro. However, these results were obtained by placing
GCs in unphysiological conditions in culture medium containing high glucose and
insulin concentrations. Moreover, existing data on insulin-responsive steroid
production in vitro by PCOS GCs vary. STUDY DESIGN, SIZE AND DURATION: Case
control experimental research comparing glucose uptake, pyruvate and lactate
production and progesterone production in vitro by GCs from three aetiological
groups, all undergoing IVF; healthy control women (Control, n = 12), women with
PCOS treated with metformin in vivo (Metformin, n = 8) and women with PCOS not
exposed to metformin (PCOS, n = 8). The study was conducted over a period of 3
years between 2007 and 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Rotterdam
criteria were used for the diagnosis of PCOS; all subjects were matched for age,
BMI and baseline FSH. Individual patient cultures were undertaken with cells
incubated in a validated, physiological, serum-free culture medium containing
doses of 0-6 mM glucose and 0-100 ng/ml insulin for 6 h and 144 h to quantify the
impact of treatments on acute and long-term metabolism, respectively, and
progesterone production. The metabolite content of spent media was measured using
spectrophotometric plate reader assay. The progesterone content of spent media
was measured by enzyme-linked immunosorbent assay. Viable GC number was
quantified after 144 h of culture by the vital dye Neutral Red uptake assay. MAIN
RESULTS AND THE ROLE OF CHANCE: Granulosa cells from women with PCOS pathology
revealed reduced pyruvate production and preferential lactate production in
addition to their reduced glucose uptake during cultures (P < 0.05). Metformin
pretreatment alleviated this metabolic lesion (P < 0.05) and enhanced cell
proliferation in vitro (P < 0.05), but cells retained a significantly reduced
capacity for progesterone synthesis compared with controls (P < 0.05).
LIMITATIONS, REASONS FOR CAUTION: Although significant treatment effects were
detected in this small cohort, further studies are required to underpin the
molecular mechanisms of the effect of metformin on GCs. WIDER IMPLICATIONS OF THE
FINDINGS: The individual patient culture strategy combined with multifactorial
experimental design strengthens the biological interpretation of the data.
Collectively, these results support the notion that there is an inherent
impairment in progesterone biosynthetic capacity of the GCs from women with PCOS.
The positive, acute metabolic effect and the negative long-term steroidogenic
effect on GCs following metformin exposure in vivo may have important
implications for follicular development and luteinized GC function when the drug
is used in clinical practice. STUDY FUNDING/COMPETING INTERESTS: No competing
interests. This work was supported by the UK Medical Research Council Grant
Reference number G0800250.
PMID- 25139177
TI - Retroperitoneal laparoscopic reimplantation of the left renal vein for nutcracker
syndrome.
AB - OBJECTIVE: To describe the feasibility of retroperitoneal laparoscopic
reimplantation of the left renal vein (LRV) for nutcracker syndrome (NCS).
PATIENTS AND METHODS: Two patients with NCS underwent the surgery. Both patients
complained of gross hematuria and flank discomfort that could not be relieved by
resting. They were placed in a supine position and 5 ports were placed in the
right abdominal wall. The procedures were performed with a retroperitoneal
approach. The LRV was transected and then reimplanted into the distal inferior
vena cava. RESULTS: The procedures were performed successfully without any major
complications. The total operation time was 105 and 120 min, respectively.
Hematuria and flank discomfort were resolved after the surgery. Ultrasonography
revealed a patent lumen without compression. CONCLUSIONS: Retroperitoneal
laparoscopic reimplantation of the LRV appears to be a feasible procedure with
satisfactory short-term outcomes.
PMID- 25139175
TI - Severe teenage acne and risk of endometriosis.
AB - STUDY QUESTION: Is there a relationship between severe teenage acne and
endometriosis? SUMMARY ANSWER: Endometriosis is positively associated with severe
teenage acne. WHAT IS KNOWN ALREADY: No studies have specifically explored a
possible association between severe acne in adolescence and risk of
endometriosis. STUDY DESIGN, SIZE, DURATION: This prospective cohort study used
data collected from 88 623 female nurses from September 1989 to June 2009 as part
of the Nurses' Health Study II (NHS II) cohort. PARTICIPANTS/MATERIALS, SETTING,
METHODS: Regression models were used to calculate hazard ratios (HRs) and
confidence intervals (CIs) for endometriosis among women with and without severe
teenage acne. Multivariate models were adjusted for established risk factors of
endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 4 382
laparoscopically confirmed endometriosis cases were documented during 1 132 272
woman-years of follow-up. Compared with women without a history of severe teenage
acne, women who had severe teenage acne had a 20% increased risk of endometriosis
(HR = 1.20, 95% CI: 1.08-1.32). The association was not affected by adjusting for
use of tetracycline or isotretinoin. LIMITATIONS AND REASONS FOR CAUTION: The HR
is likely to be underestimated since we only included endometriosis cases
confirmed by laparoscopy. Although geographically diverse, the NHS II cohort is
primarily Caucasian, which may limit generalization to more ethnically diverse
populations. WIDER IMPLICATIONS OF THE STUDY: The results of this study suggest
that severe teenage acne is associated with an increased risk of endometriosis.
As a visible and non-invasive clinical indicator, severe teenage acne may be
useful for early detection of endometriosis. We bring this counter-intuitive
association to the attention of clinicians for the benefit of the patient and an
early diagnosis of endometriosis. STUDY FUNDING/COMPETING INTEREST: This study
was funded by research grant CA176726 from the National Institute of Health. M.K.
is supported by a Marie Curie International Outgoing Fellowship within the 7th
European Community Framework Programme (#PIOF-GA-2011-302078). The funding
agencies had no role in the design of the study, in the analysis and
interpretation of the data, in the writing of the report or in the decision to
submit the paper for publication.
PMID- 25139178
TI - The (lack of) effect of alprazolam on eating behavior in anorexia nervosa: a
preliminary report.
AB - OBJECTIVE: Anxiety is a prominent symptom in anorexia nervosa (AN), and higher
pre-meal anxiety has been associated with lower caloric intake. Yet, the causal
relationship has not been assessed. We proposed that reducing anxiety with a
short acting benzodiazepine would increase caloric intake among individuals with
AN. METHOD: In a randomized, double-blind, placebo controlled cross-over study,
we administered alprazolam 0.75 mg to inpatients with AN (n = 17) and assessed
caloric intake in a laboratory test meal. Within-subject differences in caloric
intake, anxiety, and fatigue were compared between alprazolam and placebo days.
RESULTS: Caloric intake did not differ on alprazolam versus placebo (t(15) =
1.72, p = .11). Alprazolam did not reduce anxiety, but was associated with
increased fatigue. DISCUSSION: This study was not able to evaluate the causal
role of anxiety in meal intake among individuals with AN, as alprazolam did not
alter anxiety symptoms. These data further suggest that the therapeutic role for
short-acting benzodiazepines in AN is likely limited.
PMID- 25139180
TI - Photoinduced energy transfer from poly(N-vinylcarbazole) to tricarbonylchloro
(2,2'-bipyridyl)rhenium(I).
AB - This work investigates the photoinduced energy transfer from poly(N
vinylcarbazole) (PVK), as a donor material, to fac-(2,2'-bipyridyl)Re(CO)3Cl, as
a catalyst acceptor, for its potential application towards CO2 reduction.
Photoluminescence quenching experiments reveal dynamic quenching through
resonance energy transfer in solid donor/acceptor mixtures and in solid/liquid
systems. The bimolecular reaction rate constant at solution-film interfaces for
the elementary reaction of the excited state with the quencher material could be
determined as 8.8(+/-1.4)*10(11) L mol(-1) s(-1) by using Stern-Volmer
analysis. This work shows that PVK is an effective and cheap absorber material
that can act efficiently as a redox photosensitizer in combination with fac-(2,2'
bipyridyl)Re(CO)3Cl as a catalyst acceptor, which might lead to possible
applications in photocatalytic CO2 reduction.
PMID- 25139179
TI - In silico model-based inference: a contemporary approach for hypothesis testing
in network biology.
AB - Inductive inference plays a central role in the study of biological systems where
one aims to increase their understanding of the system by reasoning backwards
from uncertain observations to identify causal relationships among components of
the system. These causal relationships are postulated from prior knowledge as a
hypothesis or simply a model. Experiments are designed to test the model.
Inferential statistics are used to establish a level of confidence in how well
our postulated model explains the acquired data. This iterative process, commonly
referred to as the scientific method, either improves our confidence in a model
or suggests that we revisit our prior knowledge to develop a new model. Advances
in technology impact how we use prior knowledge and data to formulate models of
biological networks and how we observe cellular behavior. However, the approach
for model-based inference has remained largely unchanged since Fisher, Neyman and
Pearson developed the ideas in the early 1900s that gave rise to what is now
known as classical statistical hypothesis (model) testing. Here, I will summarize
conventional methods for model-based inference and suggest a contemporary
approach to aid in our quest to discover how cells dynamically interpret and
transmit information for therapeutic aims that integrates ideas drawn from high
performance computing, Bayesian statistics, and chemical kinetics.
PMID- 25139181
TI - Robust pro-inflammatory and lesser anti-inflammatory immune responses during
primary simian varicella virus infection and reactivation in rhesus macaques.
AB - Simian varicella virus (SVV) infection of non-human primates models human
varicella zoster virus (VZV) infection. Assessment of cell signaling immune
responses in monkeys after primary SVV infection, after immunosuppression and
during reactivation revealed strong pro-inflammatory responses and lesser anti
inflammatory components during varicella and reactivation. Pro-inflammatory
mediators elevated during varicella included interferon-gamma (IFN-gamma),
interleukin (IL)-6, monocyte chemoattractant protein (MCP-1), interferon
inducible T-cell alpha chemoattractant protein (I-TAC), interferon processing
protein (IP-10), and anti-inflammatory interleukin-1 Receptor antagonist (IL
1Ra). After immunosuppression and at reactivation, levels of pro-inflammatory
mediators MCP-1, eotaxin, IL-6, IL-8, MIF, RANTES (regulated-on-activation normal
T-cell expressed and secreted), and HGF (hepatocyte growth factor) were elevated,
as was the anti-inflammatory mediator IL-1Ra. Characterization of cytokine,
chemokine and growth factor responses during different stages of varicella virus
infection will facilitate immunotherapeutic and vaccine strategies.
PMID- 25139182
TI - Review of West Nile virus epidemiology in Italy and report of a case of West Nile
virus encephalitis.
AB - West Nile virus (WNV) is a flavivirus that causes neurological disorders in less
than 1 % of infected subjects. Human cases of WNV-associated fever and/or
neurological disorders have been reported in Italy since 2008. The first outbreak
occurred in the northeastern region of Italy surrounding the Po River and was
caused by the Po River lineage 1 strain, and since then, WNV infections have been
reported in several regions of central Italy. Although the virus is highly
genetically conserved, stochastic mutations in its genome may lead to the
emergence of new strains, as was observed in Italy in 2011 with the
identification of two new lineage 1 strains, the WNV Piave and WNV Livenza
strains. To help further define WNV epidemiology in Italy, we describe a case of
an Italian man living in the Po River area who developed fatal encephalitis in
2009 due to infection with the WNV Piave strain. This finding supports the notion
that the Piave strain has been circulating in this area of Italy for 2 years
longer than was previously believed.
PMID- 25139184
TI - Revealing the distribution of the atoms within individual bimetallic catalyst
nanoparticles.
AB - To be able to correlate the catalytic properties of nanoparticles with their
structure, detailed knowledge about their make-up on the atomic level is
required. Herein, we demonstrate how atom-probe tomography (APT) can be used to
quantitatively determine the three-dimensional distribution of atoms within a
Au@Ag nanoparticle with near-atomic resolution. We reveal that the elements are
not evenly distributed across the surface and that this distribution is related
to the surface morphology and residues from the particle synthesis.
PMID- 25139183
TI - Frequent utilization of the emergency department for acute heart failure
syndrome: a population-based study.
AB - BACKGROUND: Although most research on patients with acute heart failure syndrome
(AHFS) has focused on readmissions, this may provide an incomplete picture of
health-care utilization. We examined the proportion and characteristics of
patients with frequent emergency department (ED) visits for AHFS and associated
health-care utilization. METHODS AND RESULTS: A retrospective cohort study of
adults with at least 1 ED visit for AHFS between 2010 and 2011 was performed,
derived from population-based multipayer data of state ED and inpatient databases
for 2 large and diverse states, California and Florida. The analytic sample
comprised 113 033 patients with 175 491 ED visits for AHFS. During the 1-year
follow-up period, 30.8% of patients had >=2 (frequent) visits, accounting for
55.4% (95% confidence interval, 55.2-55.5%) of all ED visits for AHFS. In the
multivariable model, significant predictors of frequent ED visits were non
Hispanic black race, Hispanic ethnicity, Medicaid insurance, and lower median
household income (all P<0.001). At the visit level, patients with frequent ED
visits accounted for 55.0% (95% confidence interval, 54.8-5.3%) of all AHFS
hospitalizations via ED. Total charges for AHFS were $3.08 billion (95%
confidence interval, $3.03-3.14 billion) in Florida alone; patients with frequent
ED visits accounted for 53.3% of total charges (95% confidence interval, 53.2
53.3%). CONCLUSIONS: In this large cohort study, we found that one third (31%) of
ED patients with AHFS had frequent ED visits for this condition and that minority
race/ethnicity and lower socioeconomic status were associated with frequent ED
visits. Individuals with frequent ED visits accounted for the majority of ED
visits, hospitalizations, and hospital charges.
PMID- 25139186
TI - Identifying soluble mediators of nuclear receptor and insulin signaling may
enhance noninvasive diagnosis of fibrosis in Fatty liver disease.
PMID- 25139185
TI - Epicardial adipose tissue thickness, flow-mediated dilatation of the brachial
artery, and carotid intima-media thickness: Associations in rheumatoid arthritis
patients.
AB - AIM: The purpose of this work was to evaluate epicardial adipose tissue (EAT),
carotid intima-media thickness (CIMT), and flow-mediated dilatation (FMD) of the
brachial artery in rheumatoid arthritis (RA) patients using ultrasonographic
methods. Interrelationships between these three parameters in RA patients were
also investigated. METHODS: EAT thickness, CIMT, and FMD were measured by
ultrasonography. We measured the disease activity score (DAS28), health
assessment questionnaire (HAQ) score, and C-reactive protein (CRP) levels.
Spearman or Pearson correlation analysis was used to evaluate the association
between clinical findings, CIMT, FMD, and EAT. RESULTS: A total of 90 RA patients
[19 men, mean age 54 years (range 21-76 years)] and 59 age- and gender-matched
control subjects [17 men, mean age 54 years (range 26-80 years)] were included in
the study. Patients with RA had a mean 4.34 DAS28 points (range 0-40 points) and
the mean duration of the disease was 77.1 months (range 1-360 months). We found
that RA patients had thicker EAT (7.7 +/- 1.7 mm vs 6.2 +/- 1.8 mm, p < 0.001),
increased CIMT [0.9 (0.5-1.2) mm vs 0.6 (0.4-0.9) mm, p < 0.001], and decreased
FMD values [5.7 % (- 23.5 to 20 %) vs. 8.5 % (- 4.7 to 22.2 %), p = 0.028] when
compared to control subjects. CRP levels were significantly higher in the RA
group [0.81 (range 0.1-13.5) vs 0.22 (range 0.05-12), p < 0.001]. EAT thickness
was negatively correlated with FMD (r = - 0.26, p < 0.001) and positively
correlated with CIMT values (r = 0.52, p < 0.001). CIMT also negatively
correlated with FMD (r = - 0.29, p < 0.001). CONCLUSION: EAT can be simply
measured by echocardiography and correlated with FMD and CIMT. It can be used as
a first-line measurement for estimating burden of atherosclerosis in RA patients.
PMID- 25139188
TI - Human evolution: making the most of damage.
PMID- 25139189
TI - Pathogen genetics: temporary survival of the fittest?
PMID- 25139187
TI - Using next-generation sequencing to isolate mutant genes from forward genetic
screens.
AB - The long-lasting success of forward genetic screens relies on the simple
molecular basis of the characterized phenotypes, which are typically caused by
mutations in single genes. Mapping the location of causal mutations using genetic
crosses has traditionally been a complex, multistep procedure, but next
generation sequencing now allows the rapid identification of causal mutations at
single-nucleotide resolution even in complex genetic backgrounds. Recent advances
of this mapping-by-sequencing approach include methods that are independent of
reference genome sequences, genetic crosses and any kind of linkage information,
which make forward genetics amenable for species that have not been considered
for forward genetic screens so far.
PMID- 25139190
TI - Population genomics: a new window into the genetics of complex diseases.
PMID- 25139193
TI - The effect of protein PEGylation on physical stability in liquid formulation.
AB - The presence of micron aggregates in protein formulations has recently attracted
increased interest from regulatory authorities, industry, and academia because of
the potential undesired side effects of their presence. In this study, we
characterized the micron aggregate formation of hen egg-white lysozyme (Lyz) and
its diPEGylated (5 kDa) analog as a result of typical handling stress conditions.
Both proteins were subjected to mechanical stress in the absence and presence of
silicone oil (SO), elevated temperatures, and freeze-thaw cycles. Flow imaging
microscopy showed that PEGylated Lyz formed approximately half as many particles
as Lyz, despite its lower apparent thermodynamic stability and more loose protein
fold. Further characterization showed that the PEGylation led to a change from
attractive to repulsive protein-protein interactions, which may partly explain
the reduced particle formation. Surprisingly, the PEGylated Lyz adsorbed an order
of magnitude faster onto SO, despite being much larger in size, as determined by
small-angle X-ray scattering and dynamic light scattering measurements. Thus,
PEGylation may significantly reduce, but not prevent, micron aggregate formation
of a protein during typical handling stresses.
PMID- 25139191
TI - Carbachol-induced colonic mucus formation requires transport via NKCC1, K+
channels and CFTR.
AB - The colonic mucosa protects itself from the luminal content by secreting mucus
that keeps the bacteria at a distance from the epithelium. For this barrier to be
effective, the mucus has to be constantly replenished which involves exocytosis
and expansion of the secreted mucins. Mechanisms involved in regulation of mucus
exocytosis and expansion are poorly understood, and the aim of this study was to
investigate whether epithelial anion secretion regulates mucus formation in the
colon. The muscarinic agonist carbachol was used to induce parallel secretion of
anions and mucus, and by using established inhibitors of ion transport, we
studied how inhibition of epithelial transport affected mucus formation in mouse
colon. Anion secretion and mucin exocytosis were measured by changes in membrane
current and epithelial capacitance, respectively. Mucus thickness measurements
were used to determine the carbachol effect on mucus growth. The results showed
that the carbachol-induced increase in membrane current was dependent on NKCC1 co
transport, basolateral K(+) channels and Cftr activity. In contrast, the
carbachol-induced increase in capacitance was partially dependent on NKCC1 and
K(+) channel activity, but did not require Cftr activity. Carbachol also induced
an increase in mucus thickness that was inhibited by the NKCC1 blocker
bumetanide. However, mice that lacked a functional Cftr channel did not respond
to carbachol with an increase in mucus thickness, suggesting that carbachol
induced mucin expansion requires Cftr channel activity. In conclusion, these
findings suggest that colonic epithelial transport regulates mucus formation by
affecting both exocytosis and expansion of the mucin molecules.
PMID- 25139194
TI - Highly stretchable and conductive silver nanowire thin films formed by soldering
nanomesh junctions.
AB - Silver nanowires (AgNWs) have been widely used for stretchable and foldable
conductors due to their percolating network nanostructure. To enhance the
mechanical strength of AgNW thin films under extreme stretching conditions, in
this study, we utilize a simple chemical reaction to join AgNW network
connections. Upon applying a reactive ink over AgNW thin films, silver
nanoparticles are preferentially generated over the nanowire junctions and solder
the nanomesh structures. The soldered nanostructure reinforces the conducting
network and exhibits no obvious change in electrical conductivity in the
stretching or rolling process with elongation strains up to 120%. Several
examples are also demonstrated to show potential applications of this material in
stretchable electronic devices.
PMID- 25139192
TI - Effect of high-fat diet on rat myometrium during pregnancy-isolated myometrial
mitochondria are not affected.
AB - Laboring women with elevated body mass index (BMI) have an increased risk of
inefficient uterine labor contractions, and despite the significance of
mitochondria in the production of energy to drive uterine contractions,
mitochondrial function in the myometrium with reference to the BMI has not been
explored. The objective of this study was to determine whether obesity prior to
and during gestation affects oxidative capacity and/or morphology of mitochondria
in the myometrium at term in an animal model. Rat dams were fed for 47 days prior
to impregnation and during gestation with either (1) a regular chow diet, (2) a
low-fat high-carbohydrate diet, or (3) a high-fat low-carbohydrate diet (n = 10
in each group). On day 20 of gestation, corresponding to term pregnancy, total
hysterectomy was performed with subsequent examination of the function and
morphology of myometrial mitochondria. Body composition was regularly assessed by
quantitative magnetic resonance imaging, and blood sampling was done prior to
diet assignment, impregnation, and hysterectomy. Dams on the high-fat low
carbohydrate diet achieved higher fat percentage compared to rats on the regular
chow diet (p < 0.05). Maximal oxygen consumption, phosphate/oxygen ratio, or the
amount of mitochondria per gram of myometrium did not differ between the three
feeding groups. Electron microscopic examinations did not reveal any
morphological differences in mitochondria between groups; however, a previously
undescribed subsarcolemmal localization of the mitochondria in the myocyte was
identified. We did not find evidence of altered myometrial mitochondrial function
or morphology in this animal model of obesity prior to and during pregnancy.
PMID- 25139195
TI - Lack of effect of the glucagon-like peptide-1 receptor agonist liraglutide on
psoriasis in glucose-tolerant patients--a randomized placebo-controlled trial.
AB - BACKGROUND: It has been proposed that glucagon-like peptide-1 receptor (GLP-1R)
agonists used for the treatment of patients with type 2 diabetes might also
improve their psoriasis. OBJECTIVE: To assess the efficacy and safety of the GLP
1R agonist liraglutide in glucose-tolerant patients with plaque psoriasis.
METHODS: A total of 20 obese (body mass index > 25 kg/m(2)), glucose-tolerant
patients with plaque psoriasis (psoriasis area and severity index (PASI) of at
least 8) were randomized 1:1 to once-daily subcutaneous injections with
liraglutide or placebo for an 8-week period. The primary end points were
improvement in PASI and dermatology life quality index (DLQI). Secondary end
points included changes in weight and high sensitive C-reactive protein (hsCRP)
levels, as well as adverse events. RESULTS: After 8 weeks of treatment, no
significant change in PASI was found in the liraglutide group (mean+/-standard
deviation: -2.6 +/- 2.1) compared with the placebo group (-1.3 +/- 2.4) (P =
0.228). No difference in DLQI was observed between the groups [-2.5 +/- 4.4
(liraglutide) vs. -3.7 +/- 4.8 (placebo); P = 0.564]. HsCRP did not change in any
of the groups (0.26 +/- 1 (placebo) vs. 0.25 +/- 2.2 (liraglutide); P = 0.992).
Liraglutide treatment resulted in a bodyweight loss of 4.7 +/- 2.5 kg compared
with 1.6 +/- 2.7 kg in the placebo group (P = 0.014) accompanied by decreased
cholesterol levels. No serious adverse events occurred during the 8-week
observation period. The most common complaint was transient nausea, which
occurred in 45% of the liraglutide-treated patients but in none from the placebo
group. CONCLUSION: Liraglutide treatment for 8 weeks did not significantly change
PASI, DLQI, or hsCRP in a small group of glucose-tolerant obese patients with
plaque psoriasis compared with placebo. A significant weight loss and decrease in
cholesterol levels was observed in liraglutide-treated patients.
PMID- 25139196
TI - Neoadjuvant chemotherapy for different molecular breast cancer subtypes: a
retrospective study in Russian population.
AB - The aim of this retrospective study was to evaluate the objective clinical
response (cOR), pathological complete response (pCR), and progression-free
survival (PFS) in 231 Russian patients with four subtypes of breast cancer
treated with neoadjuvant chemotherapy. About 130 (56.3 %) patients received
anthracycline-based, 56 (24.2 %) capecitabine-containing (CAX), 28 (12.1 %)
taxotere and 17 (7.4 %) non-anthracycline-containing chemotherapy regimens at the
Tomsk Cancer Research Institute between 2000 and 2010. Tumors were subtyped
according to the hormone receptor (HR) and human epidermal growth factor receptor
2 (HER2) immunohistochemical data. The majority of tumors (48.9 %) were ER+/PR+
and HER2-negative (HR+/HER2-), 10.4 % were ER+ PR+ and HER2-positive (HR+/HER2+),
9.1 % were ER-/PR- and HER2-overexpressed (HER2-enriched) and 31.6 % were ER-/PR-
and HER2-negative (triple negative). Both cOR and pCR were significantly higher
in the triple-negative tumors compared to the other subtypes (P = 0.021 and P =
0.033, respectively). Among the four chemotherapy regimens, only CAX regimen had
a predictive value for cOR (HR 2.30, 95 % CI 1.16-4.58, P = 0.009). Multivariate
regression analysis showed that the triple-negative subtype (HR 2.54, 95 % CI
1.06-1.42, P = 0.011) and CAX regimen (HR 3.01, 95 % CI 1.01-1.46, P = 0.002)
were significantly associated with cOR. No association between patient's PFS and
a tumor subtype was observed. However, there was a trend for a prolonged PFS
among patients with cOR (P = 0.056). Our data indicate a potentially better
prognosis for triple-negative breast cancer patients if treated with the CAX
neoadjuvant regimen.
PMID- 25139198
TI - Re: Eric A. Klein, Matthew R. Cooperberg, Cristina Magi-Galluzzi, et al. A 17
gene assay to predict prostate cancer aggressiveness in the context of gleason
grade heterogeneity, tumor multifocality, and biopsy undersampling. Eur urol
2014;66:550-60.
PMID- 25139197
TI - Preoperative Prostate-specific Antigen Isoform p2PSA and Its Derivatives, %p2PSA
and Prostate Health Index, Predict Pathologic Outcomes in Patients Undergoing
Radical Prostatectomy for Prostate Cancer: Results from a Multicentric European
Prospective Study.
AB - BACKGROUND: Currently available predictive models fail to assist clinical
decision making in prostate cancer (PCa) patients who are potential candidates
for radical prostatectomy (RP). New biomarkers would be welcome. OBJECTIVE: To
test the hypothesis that prostate-specific antigen (PSA) isoform p2PSA and its
derivatives, percentage of p2PSA to free PSA (%p2PSA) and the Prostate Health
Index (PHI), predict PCa characteristics at final pathology. DESIGN, SETTING, AND
PARTICIPANTS: An observational prospective multicentre European study was
performed in 489 consecutive PCa patients treated with RP. Total PSA (tPSA), free
PSA (fPSA), and p2PSA levels were determined. The %fPSA [(fPSA / tPSA) * 100],
%p2PSA [(p2PSA pg/ml) / (fPSA ng/ml * 1000) * 100], and PHI [(p2PSA / fPSA) *
?tPSA] were calculated. INTERVENTION: Open or robot-assisted RP. OUTCOME
MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression models were fitted to
test the predictors of pT3 stage and/or pathologic Gleason score (GS) >=7 and to
determine their predictive accuracy. The base multivariable model included tPSA,
digital rectal examination, biopsy GS, and percentage of positive biopsy cores.
Decision curve analysis provided an estimate of the net benefit obtained using
p2PSA, %p2PSA, or PHI. RESULTS AND LIMITATIONS: Overall, 344 patients (70%) were
affected by pT3 disease or pathologic GS >=7; pT3 disease and pathologic GS >=7
were present in 126 patients (26%). At univariable analysis, p2PSA, %p2PSA, and
PHI were significant predictors of pT3 disease and/or pathologic GS >=7 (all p <=
0.001). The inclusion of PHI significantly increased the accuracy of the base
multivariable model by 2.3% (p=0.003) and 2.4% (p=0.01) for the prediction of pT3
disease and/or pathologic GS >=7, respectively. However, at decision curve
analysis, models including PHI did not show evidence of a greater clinical net
benefit. CONCLUSIONS: Both %p2PSA and PHI are significant predictors of
unfavourable PCa characteristics at final pathology; however, %p2PSA and PHI did
not provide a greater net benefit for clinical decision making. PATIENT SUMMARY:
Prostate-specific antigen (PSA) isoform p2PSA and its derivatives, percentage of
p2PSA to free PSA and the Prostate Health Index, are associated with adverse
characteristics of prostate cancer; however, these biomarkers provided only a
slight net benefit for clinical decision making.
PMID- 25139199
TI - Reply from authors re: David Margel. Metformin to prevent prostate cancer: a call
to unite. Eur urol 2014;66:1021-2.
PMID- 25139201
TI - Mechanisms of remembering the past and imagining the future--new data from
autobiographical memory tasks in a lifespan approach.
AB - We investigated the episodic/semantic distinction in remembering the past and
imagining the future and explored cognitive mechanisms predicting events'
specificity throughout the lifespan. Eighty-three 6- to 81-year-old participants,
divided into 5 age groups, underwent past, present and future episodic (events'
evocation) and semantic (self-descriptions) autobiographical tasks and a
complementary cognitive test battery (executive functions, working and episodic
memory). The main results showed age effects on episodic events' evocation
indicating an inverted U function (i.e., developmental progression from 6 to
21years and aging decline). By contrast, age effects were slighter on self
descriptions while self-defining events' evocation increased with age.
Furthermore, age effects on episodic events' evocation were mainly mediated by
age effects on cognitive functions and personal semantics. These new findings
indicate a developmental and aging episodic/semantic distinction for both
remembering the past and imagining the future, and suggest that above
similarities, these abilities could have a fundamentally different basis.
PMID- 25139200
TI - Radiologically determined orthodontically induced external apical root resorption
in incisors after non-surgical orthodontic treatment of class II division 1
malocclusion: a systematic review.
AB - This study aims to critically evaluate orthodontically induced external apical
root resorption (OIEARR) in incisors of patients undergoing non-surgical
orthodontic treatment of class II division 1 malocclusion by a systematic review
of the published data. An electronic search of two databases was performed; the
bibliographies of relevant articles were also reviewed. Studies were included if
they examined the amount of OIEARR in incisors produced during non-surgical
orthodontic treatment of individuals with class II division I malocclusion in the
permanent dentition. Individuals had no previous history of OIEARR, syndromes,
pathologies, or general diseases. Study selections, risk of bias assessment, and
data extraction were performed in duplicate. Eight studies of moderate
methodological quality were finally included. An increased prevalence (65.6% to
98.1%) and mild to moderate severity of OIEARR (<4 mm and <1/3 original root)
were reported. No sex difference in root resorption was found. For the maxillary
incisors, there was no evidence that either the central or lateral incisor was
more susceptible to OIEARR. A weak to moderate positive correlation between
treatment duration and root resorption, and anteroposterior apical displacement
and root resorption was found. Current limited evidence suggests that non
surgical comprehensive orthodontic treatment to correct class II division 1
malocclusions causes increased prevalence and severity of OIEARR the more the
incisor roots are displaced and the longer this movement takes.
PMID- 25139203
TI - Antiretroviral therapy initiation in an Australian cohort: implications for
increased use of antiretroviral therapy.
AB - Human immunodeficiency virus (HIV) management is entering a "universal test and
treat" phase, although the benefits from this approach in developed world
scenarios are uncertain. We analyzed 79 combination anti-retroviral therapy
(cART)-naive HIV-positive individuals who were intensively prospectively followed
from 2004 to 2013. We studied HIV-related illnesses, potential HIV transmissions,
impact on sexual behavior, and factors impeding earlier cART initiation. Sixty
eight (86 %) subjects commenced cART at a mean of 6.0 years after diagnosis: 71 %
with a CD4 T-cell count <350 cells/MUl. A significant minority of subjects (29 %)
resisted initiation of cART despite physician recommendation for a mean of 18
months. Only one HIV-related illness occurred in a patient who had not previously
recorded a CD4 T-cell count <500 cell/MUl, totaling 195 person-years of
observation. A 40 % increase in sexually transmitted infections (STIs) occurred
after commencing cART. We detected six HIV transmissions in our cohort, all of
which were before initiating cART and 5 of them had a prior CD4 T-cell count <500
cells/MUl. Illnesses related to cART deferral were rare and most HIV
transmissions we detected occurred in people with a prior CD4 T-cell count <500
cells/MUl. Our study raises concerns about increasing STI rates after cART
initiation. Focusing resources on cART initiation among patients with CD4 T-cell
counts <500 cells/MUl and enhancing safe sexual practices should remain a
priority.
PMID- 25139202
TI - Multicenter phase II study of a combination of cyclosporine a, methotrexate and
mycophenolate mofetil for GVHD prophylaxis: results of the Chinese Bone Marrow
Transplant Cooperative Group (CBMTCG).
AB - BACKGROUND: Improvement of current GVHD prophylactic therapies remains an
important goal in the allo-HSCT. We have described a novel prophylaxis regimen in
a single institution trial. The Chinese Bone Marrow Transplant Cooperative Group
(CBMTCG) initiated a phase II multicenter study. METHODS: The study was designed
as a prospective, single arm phase II open-label, multicenter clinical trial. The
primary endpoint was improvement of aGVHD by 25% over historical control (40%) in
Chinese patients. 508 patients were enrolled. All of the patients received
cyclosporine A (CsA), methotrexate (MTX) and mycophenolate mofetil (MMF) (0.5-1.0
g daily for 30 days) as GVHD prophylaxis regimen. RESULTS: The primary endpoint
was met with cumulative incidences of grades 2 to 4 and grades 3 to 4 aGVHD of
23.2% and 10.3%, respectively. Incidence for cGVHD was 67.4%. The non-relapse
mortality (NRM) rate was 18.4% at 2 years. The probabilities of leukemia free
survival (LFS) for non-advanced stage and advanced stage patients at 2 years were
69.7% and 44.8% respectively (p = 0.000). Recipient age >= 40 years, advanced
stage and Busulfan-Fludarabine(BuFlu) conditioning regimen were identified as
major risk factors for aGVHD. Recipient age >= 40 years, BuFlu conditioning
regimens, female donor/male recipient and prior aGVHD were associated with cGVHD.
Despite lower RM (relapse mortality), patients with grade 2-4 aGVHD had higher
NRM and worse OS and LFS compared to patients with grade 0-1 aGVHD. In contrast,
patients with cGVHD had better OS and LFS and lower RM compared to patients
without cGVHD. CONCLUSION: The novel GVHD regimen decreased the risk for aGVHD by
42% without improving the risk for cGVHD compared to historical controls.
Development of aGVHD was associated with worse OS and LFS as well as higher NRM.
In contrast, cGVHD was associated with improved OS and LFS likely attributed to a
GVL effect.
PMID- 25139204
TI - A common copy number variation polymorphism in the CNTNAP2 gene: sexual
dimorphism in association with healthy aging and disease.
AB - BACKGROUND: New therapeutic targets are needed to fight aging-related diseases
and increase life span. A new female-specific association with diseases and
limited survival past 80 years was recently reported for a copy number variation
(CNV) in the CNTNAP4 gene from the neurexin superfamily. OBJECTIVE: We asked
whether there are CNVs that are associated with aging phenotypes within other
genes from the neurexin superfamily and whether this association is sex specific.
METHODS: Select CNV polymorphisms were genotyped with proprietary TaqMan qPCR
assays. RESULTS: A case/control study, in which a group of 81- to 90-year-old
community-dwelling Caucasians with no chronic diseases (case) was compared to a
similar control group of 65- to 75-year-olds, revealed a negative association
with healthy aging for the ins allele of common esv11910 CNV in the CNTNAP2 gene
(n = 388; OR = 0.29, 95% CI: 0.14-0.59, p = 0.0004 for males, and OR = 0.82, 95%
CI: 0.42-1.57, p = 0.625 for females). This male-specific association was
validated in a study of an independent group of 76- to 80-year-olds. To look for
a corresponding positive association of the allele with aging-related diseases,
two case subgroups of 81- to 90-year-olds, one composed of individuals with
cognitive impairment and the other with various diseases not directly related to
the nervous system, such as cardiovascular diseases, etc., were compared to a
healthy control subgroup of the same age. A positive male-specific association
was found for both cases (OR = 2.75, p = 0.008 for association with cognitive
impairment, and OR = 3.18, p = 0.002 for other diseases combined). CONCLUSIONS: A
new male-specific association with aging is reported for a CNV in the CNTNAP2
gene. The polymorphism might be useful for diagnosing individual genetic
predispositions to healthy aging versus aging complicated by chronic diseases.
PMID- 25139205
TI - Drug prescription by telephone consultation in Danish out-of-hours primary care:
a population-based study of frequency and associations with clinical severity and
diagnosis.
AB - BACKGROUND: Danish general practitioners (GPs) answer all calls to the out-of
hours primary care service. About 60% of the calls are terminated on the
telephone through provision of medical advice and prescription of medication.
Nevertheless, little is known about the prescription patterns of telephone
consultations, such as prescription frequency and indications for drug use. Our
aim was to examine the characteristics of patients and GPs in telephone
consultations resulting in drug prescription. METHODS: The study was based on a
12-month survey on reasons for encounter in the Danish out-of-hours primary care
service. A total of 385 GPs (55.5% of all GPs from Central Denmark Region on duty
during a year) participated in answering electronic pop-up questionnaires
integrated in the electronic patient administration system. The questionnaires
contained items on reasons for encounter (e.g. existing chronic disease or new
health problem), diagnoses, and GP-assessed severity of the health problem. Data
on time of contact, patient gender and age, and prescribed medication (Anatomic
Therapeutic Chemical classifications) for telephone consultations were obtained
from the patient administration system. Differences in characteristics of
patients, general practitioners, and contacts were examined, and associations
with prescribed medication were analysed using a multivariate analysis with
prevalence ratios. RESULTS: Medication was prescribed in 19.9% of the included
4,173 telephone consultations; antibiotics and analgesics were prescribed most
frequently (10.8% and 2.5%, respectively). GPs tended to assess contacts
resulting in antibiotic prescription as more severe than other contacts. For high
severity contacts, there was a lower likelihood for prescription (prevalence
ratio = 0.28 (0.16-0.47)). Children aged 0-4 years had lower probability of
receiving a prescription compared with patients aged 18-40 years. The
prescription rate was highest during the first four hours of the opening hours of
the out-of-hours primary care service. CONCLUSION: One in five of all telephone
consultations involved drug prescription; antibiotics constituted half of these
prescriptions. Drug prescription by telephone was less likely to be offered in
cases involving 'severe' reason for encounter or children. This study calls for
further studies of drug prescriptions issued via out-of-hours primary care
telephone consultations.
PMID- 25139206
TI - Prenatal exposure to perfluoroalkyl substances and the risk of congenital
cerebral palsy in children.
AB - Perfluoroalkyl substances (PFASs) are persistent pollutants and endocrine
disruptors that may affect fetal brain development. We investigated whether
prenatal exposure to PFASs increases the risk of congenital cerebral palsy (CP).
The source population for this study includes 83,389 liveborn singletons and
mothers enrolled in the Danish National Birth Cohort during 1996-2002. We
identified 156 CP cases by linking the cohort to the Danish National Cerebral
Palsy Register, and we randomly selected 550 controls using a case-cohort design.
We measured 16 PFASs in maternal plasma collected in early or midpregnancy, and 6
PFASs were quantifiable in more than 90% of the samples. We found a higher risk
of CP in boys with higher maternal PFAS levels; per 1-unit (natural-log ng/mL)
increase, the risk ratios were 1.7 (95% confidence interval: 1.0, 2.8) for
perfluorooctane sulfonate and 2.1 (95% confidence interval: 1.2, 3.6) for
perfluorooctanoic acid. We also observed a dose-response pattern of CP risk in
boys per quartile of maternal level of perfluorooctane sulfonate and
perfluorooctanoic acid (P for trend < 0.01). PFASs were associated with both
unilateral and bilateral spastic CP subphenotypes. No association between PFASs
and CP was found in girls. Prenatal exposures to PFASs may increase the risk of
CP in boys, but the finding is novel and replication is needed.
PMID- 25139207
TI - Ozone and daily mortality rate in 21 cities of East Asia: how does season modify
the association?
AB - Previous studies in East Asia have revealed that the short-term associations
between tropospheric ozone and daily mortality rate were strongest in winter,
which is opposite to the findings in North America and Western Europe. Therefore,
we investigated the season-varying association between ozone and daily mortality
rate in 21 cities of East Asia from 1979 to 2010. Time-series Poisson regression
models were used to analyze the association between ozone and daily nonaccidental
mortality rate in each city, testing for different temperature lags. The best
fitting model was obtained after adjustment for temperature in the previous 2
weeks. Bayesian hierarchical models were applied to pool the city-specific
estimates. An interquartile-range increase of the moving average concentrations
of same-day and previous-day ozone was associated with an increase of 1.44% (95%
posterior interval (PI): 1.08%, 1.80%) in daily total mortality rate after
adjustment for temperature in the previous 2 weeks. The corresponding increases
were 0.62% (95% PI: 0.08%, 1.16%) in winter, 1.46% (95% PI: 0.89%, 2.03%) in
spring, 1.60% (95% PI: 1.03%, 2.17%) in summer, and 1.12% (95% PI: 0.73%, 1.51%)
in fall. We found significant associations between short-term exposure to ozone
and higher mortality rate in East Asia that varied considerably from season to
season with a significant trough in winter.
PMID- 25139209
TI - Smoking decreases structural and functional resilience in the subgingival
ecosystem.
AB - AIMS: Dysbiotic microbial communities underlie the aetiology of several oral
diseases, especially in smokers. The ability of an ecosystem to rebound from the
dysbiotic state and re-establish a health-compatible community, a characteristic
known as resilience, plays an important role in susceptibility to future disease.
The present investigation was undertaken to examine the effects of smoking on
colonization dynamics and resilience in marginal and subgingival biofilms.
MATERIALS AND METHODS: Marginal and subgingival plaque and gingival crevicular
fluid samples were collected from 25 current and 25 never smokers with pre
existing gingivitis at baseline, following resolution, after 1, 2 4, 7, 14 and 21
days of undisturbed plaque formation and following resolution. 16S cloning and
sequencing was used for bacterial identification and multiplexed bead-based flow
cytometry was used to quantify the levels of 27 immune mediators. RESULTS:
Smokers demonstrated an early pathogenic colonization that led to sustained
pathogen enrichment with periodontal and respiratory pathogens, eliciting a
florid immune response. Smokers also demonstrated greater abundance of pathogenic
species, poor compositional correlation between marginal and subgingival
ecosystems, and significantly greater pro-inflammatory responses following
resolution of the second episode of disease. CONCLUSIONS: The ability of the
subgingival microbiome to "reset" itself following episodes of disease is
decreased in smokers, thereby lowering the resilience of the ecosystem and
decreasing its resistance to future disease.
PMID- 25139210
TI - Single-incision laparoscopic cholecystectomy for cholecystitis requiring
percutaneous transhepatic gallbladder drainage.
AB - PURPOSE: Single-incision laparoscopic cholecystectomy (SILC) has been performed
for patients with gallbladder stones but without acute cholecystitis. We report
our experience of performing SILC for patients with cholecystitis requiring
percutaneous transhepatic gallbladder drainage (PTGBD). METHODS: We performed
SILC via an SILS-Port with additional 5-mm forceps through an umbilical incision
in ten patients with cholecystitis requiring PTGBD. RESULTS: All procedures were
completed successfully. The mean operative time was 124 min (range 78-169 min)
and there were no intraoperative or postoperative complications. The mean
postoperative hospital stay was 2.7 days. All patients were satisfied with the
cosmetic results. CONCLUSIONS: Our procedure may represent an alternative to
conventional laparoscopic cholecystectomy (CLC) for patients who fervently demand
the cosmetic advantages, despite cholecystitis requiring PTGBD. SILC should be
performed carefully to avoid bile duct injury because the only advantage of SILC
over CLC is cosmetic.
PMID- 25139211
TI - Current status of third-generation implantable left ventricular assist devices in
Japan, Duraheart and HeartWare.
AB - Recently, left ventricular assist devices (LVADs) have become a viable
therapeutic approach as a bridge to cardiac transplantation, as well as
destination therapy or as part of the bridge to recovery. In Japan, paracorporeal
pneumatic devices are the only choice for such therapy, as implantable LVADs are
not yet generally available due to device lag, which represents a serious problem
in this field. Clinical trials of four different continuous-flow pumps, both
axial and centrifugal flow types, were completed at about the same time, and two
of those devices, DuraHeart and EVAHEART, have already been approved for use in
Japan. Thus, reports of advanced treatment for severe heart failure with these
devices are expected. The DuraHeart (Terumo Heart, Ann Arbor, MI, USA) and
another device named the HeartWare (HeartWare Inc, Miami Lakes, FL, USA) are so
called third-generation devices, as they have achieved miniaturization and
improvements in performance from the use of magnetic levitation. Based on our
experiences from both clinical research and experimental use, we herein discuss
the DuraHeart and HeartWare devices, with a focus on the clinical outcomes and
management strategies. Because of the long waiting period for heart
transplantation in Japan, these two devices are considered to have important
roles in the near future for the treatment of severe heart failure, and a
comprehensive strategy for LVAD therapy including such third-generation
implantable devices is expected.
PMID- 25139208
TI - Effect of different human papillomavirus serological and DNA criteria on vaccine
efficacy estimates.
AB - Two trials of clinically approved human papillomavirus (HPV) vaccines, Females
United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE I/II) and the
Papilloma Trial Against Cancer in Young Adults (PATRICIA), reported a 22%
difference in vaccine efficacy (VE) against cervical intraepithelial neoplasia
grade 2 or worse in HPV-naive subcohorts; however, serological testing methods
and the HPV DNA criteria used to define HPV-unexposed women differed between the
studies. We applied previously described methods to simulate these HPV-naive
subcohorts within the Costa Rica HPV16/18 Vaccine Trial and assessed how these
criteria affect the estimation of VE. We applied 2 enzyme-linked immunosorbent
assay (ELISA) thresholds for HPV16 and HPV18 seropositivity (8 and 7 ELISA
units/mL, respectively, for PATRICIA; 54 and 65 ELISA units/mL, respectively, for
FUTURE I/II (to approximate the competitive Luminex immunoassay)) and 2 criteria
for HPV DNA positivity (12 oncogenic HPV types, plus HPV66 and 68/73 for
PATRICIA; or plus HPV6 and 11 for FUTURE I/II). VE was computed in the 2 naive
subcohorts. Using the FUTURE I/II and PATRICIA criteria, VE estimates against
cervical intraepithelial neoplasia grade 2 or worse, regardless of HPV type, were
69.0% (95% confidence interval: 40.3%, 84.9%) and 80.8% (95% confidence interval:
52.6%, 93.5%), respectively (P = 0.1). Although the application of FUTURE I/II
criteria to our cohort resulted in the inclusion of more sexually experienced
women, methodological differences did not fully explain the VE differences.
PMID- 25139212
TI - Appearance deceives: unusual pneumothorax: traumatic phrenic nerve paralysis.
PMID- 25139213
TI - Cardiac involvement in chronic progressive external ophthalmoplegia.
AB - Myocardial involvement has not been extensively investigated in mitochondrial
myopathies. The aim of the study was to assess the myocardial morpho-functional
changes in patients with chronic progressive external ophthalmoplegia (PEO).
Twenty patients with PEO and 20 controls underwent standard echocardiography with
tissue Doppler imaging (TDI) and integrated backscatter (IBS) analyses. These
techniques are capable of providing non-invasively the early, subtle structural
and functional changes of the myocardium. TDI myocardial systolic (Sm) and early
(Em) and late (Am) diastolic velocities of left ventricular walls were
determined. The systo-diastolic variation of IBS was also determined. Patients
with PEO exhibited lower Sm, lower Em, and higher Am, and a reduced Em/Am ratio
than controls (p<0.001 for all) at interventricular septum and lateral wall
levels. In PEO patients, septal and posterior wall cyclic variations of IBS were
significantly lower than those in controls (p<0.001). Patients with PEO showed
myocardial wall remodeling characterized by increased fibrosis and early left
ventricular systo-diastolic function abnormalities. Although cardiac involvement
in PEO is generally considered to be limited to the cardiac conduction system,
left ventricular dysfunction may be present and should receive more attention in
the management of these patients.
PMID- 25139214
TI - Admission of hematopoietic cell transplantation patients to the intensive care
unit at the Pontificia Universidad Catolica de Chile Hospital.
AB - Patients undergoing hematopoietic cell transplantation (HCT) can have
complications that require management in the intensive care unit (ICU). We
conducted a retrospective study of patients undergoing HCT between 2007 and 2011
with admission to the ICU. We analyzed 97 patients, with an average age of 37
(range, 15 to 68). The main indications for HCT were hematologic malignancies
(84%, n = 82). Ninety percent (n = 87) received myeloablative conditioning.
Thirty-one percent were admitted (autologous transplant recipients 15%,
allogeneic transplant recipients 34%, and umbilical cord blood [UCB] transplant
recipients 48%) with an average length of stay of 19 days (range, 1 to 73 days).
The average time between transplantation and transfer was 15 days. The main
causes of admission were acute respiratory failure (63%) and septic shock (20%).
ICU mortality was 20% for autologous transplantations and 64% for allogeneic
transplantations (adult donor and UCB combined). On average, patients died 108
days after the transplantation (range, 4 to 320 days). One-year overall survival,
comparing patients entering the ICU with those never admitted, was 16% versus 82%
(P < .0001) for allogeneic transplantations (adult donor and UCB combined) and
80% versus 89% (P = not significant) for autologous transplantations. Acute graft
versus-host disease was significantly associated with death in ICU after UCB HCT.
ICU support is satisfactory in about one half of patients admitted, characterized
by a short and medium term prognosis not as unfavorable as has been previously
reported.
PMID- 25139215
TI - The outcome of allogeneic hematopoietic cell transplantation for children with
FMS-like tyrosine kinase 3 internal tandem duplication-positive acute myelogenous
leukemia.
AB - FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) is a somatic
mutation associated with poor outcome when treated with chemotherapy alone. In
children, hematopoietic stem cell transplantation (HSCT) is recommended, but very
limited data on outcome are reported. We determined the outcome of 29 children
with FLT3/ITD-positive acute myelogenous leukemia (AML) who underwent allogeneic
HSCT in 4 pediatric centers. Eleven patients (38%) received matched related donor
hematopoietic stem cells and 18 (62%) received alternative donors. Eighteen
patients (62%) received total body irradiation (TBI)-based regimens. No patients
experienced transplantation-related mortality. Eleven patients (38%) experienced
relapsed disease. The cumulative incidence of relapse at 2 years was 34.7% (95%
confidence interval [CI], 20.4% to 54.9%). Two-year disease-free survival (DFS)
and overall survival (OS) were 65.3% (95% CI, 45.1% to 79.6%) and 82.2% (95% CI,
58.5% to 91.3%), respectively. There was no difference in the DFS of patients who
received transplants from related donors versus the DFS of those who received
transplants from alternative donors (hazard ratio [HR], 2.64; 95% CI, .79 to
8.76; P = .10), using univariate analysis. Patients with higher FLT3/ITD ratio at
diagnosis had significantly worse DFS (HR, 1.42; 95% CI, 1.04 to 1.93; P = .03).
The use of TBI in the preparative regimen was associated with superior DFS (HR,
.29; 95% CI, .08 to .99; P = .04) and OS (HR, .07; 95% CI, .01 to .62; P = .002).
We conclude that allogeneic HSCT improves DFS and OS in children with FLT3/ITD
positive AML compared with what has been reported in those treated with
chemotherapy alone.
PMID- 25139217
TI - Cytomegalovirus infection in patients who underwent allogeneic hematopoietic stem
cell transplantation in Portugal: a five-year retrospective review.
AB - Cytomegalovirus (CMV) infection is 1 of the leading causes of morbidity and
mortality after allogeneic hematopoietic stem cell transplantation (aHSCT),
mainly within the first 100 days after transplantation. We aimed to characterize
CMV infection in a cohort of 305 patients with different malignancies undergoing
aHSCT at the Portuguese Institute of Oncology of Porto between January 2008 and
December 2012. In total, 184 patients (60.3%) developed CMV infection, mainly
viral reactivations rather than primary infections (96.2% versus 3.8%,
respectively). The majority of patients (166 of 184) developed CMV infection
<=100 days after transplantation, with median time to infection of 29 days
(range, 0 to 1285) and median duration of infection of 10 days (range, 2 to 372).
Multivariate analysis revealed that CMV infection was increased in donor (D)
/recipient (R)+ and D+/R+ (odds ratio [OR], 10.5; 95% confidence interval [CI],
4.35 to 25.4; P < .001) and in patients with mismatched or unrelated donors (OR,
2.54; 95% CI, 1.34 to 4.80; P = .004). Cox regression model showed that the risk
of death was significantly increased in patients >38 years old (OR, 1.89; 95% CI,
1.14 to 3.12; P = .0137), who underwent transplantation with peripheral blood
(OR, 3.02; 95% CI, 1.33 to 6.86; P = .008), with mismatched or unrelated donor
(OR, 2.16; 95% CI, 1.48 to 3.13; P < .001), and who developed CMV infection (OR,
1.76; 95% CI, 1.07 to 2.90; P = .025). Moreover, patients who developed CMV
infection had a significantly reduced median post-transplantation survival (16
versus 36 months; P = .002).
PMID- 25139218
TI - Maternal serum PAPP-A as an early marker of obstetric complications?
AB - OBJECTIVE: The aim of this study was to investigate whether low first-trimester
PAPP-A levels are associated with an adverse pregnancy outcome. MATERIALS AND
METHODS: A retrospective case-control study was carried out using a Down's
syndrome assays database over a 6-year period, between the 8th and 11th week of
pregnancy. There were 164 women with PAPP-A multiples of median (MoM) levels <0.3
and 1,640 women with PAPP-A MoM levels >=0.3 who served as a control group.
Outcome measures were the prevalence of miscarriages, gestational hypertension,
preeclampsia, pre-term delivery, gestational diabetes and intrauterine growth
retardation in both groups. RESULTS: The two groups significantly differed only
for miscarriages: 29 (17.7%) vs. 159 (9.7%), p = 0.04, OR 1.7; gestational
hypertension: 15 (9.1%) vs. 74 (4.5%), p = 0.02, OR 2.1, and preeclampsia: 9
(5.5%) vs. 29 (1.8%), p = 0.02, OR 2.5. DISCUSSION: Even if in this study the
PAPP-A cutoff considered was lower and was assayed in an earlier period compared
with other studies, the detection rate for adverse pregnancy outcomes did not
improve.
PMID- 25139216
TI - Safety and efficacy of targeted-dose busulfan and bortezomib as a conditioning
regimen for patients with relapsed multiple myeloma undergoing a second
autologous blood progenitor cell transplantation.
AB - Patients with multiple myeloma (MM) who relapse after autologous transplantation
have limited therapeutic options. We conducted a prospective, multicenter, phase
IIa study to investigate the safety and efficacy of i.v. busulfan (Bu) in
combination with bortezomib as a conditioning regimen for a second
autotransplantation. Because a safe Bu exposure was unknown in patients receiving
this combination, Bu was initially targeted to a total area under the
concentration-time curve (AUC) of 20,000 MUM * minute. As no concentration
limiting toxicity was observed in 6 patients, this Bu exposure was utilized in
the following treatment cohort (n = 24). Individualized Bu dose, based on test
dose .8 mg/kg pharmacokinetics (PK), was administered daily for 4 consecutive
days starting 5 days before transplantation, followed by a single dose of
bortezomib (1.3 mg/m(2)) 1 day before transplantation. The total mean dose of
i.v. Bu (including the test dose and 4-day administration) was 14.2 mg/kg
(standard deviation = 2.48; range, 8.7 to 19.2). Confirmatory PK demonstrated
that only 2 of 30 patients who underwent transplantation were dosed outside the
Bu AUC target and dose adjustments were made for the last 2 doses of i.v. Bu. The
median age was 59 years (range, 48 to 73). Median time from first to second
transplantation was 28.0 months (range, 12 to 119). Of 26 evaluable patients, 10
patients attained a partial response (PR) or better at 3 months after
transplantation, with 2 patients attaining a complete response. At 6 months after
transplantation, 5 of 12 evaluable patients had maintained or improved their
disease status. Median progression-free survival was 191 days, whereas median
overall survival was not reached during the study period. The most common grade 3
and 4 toxicities were febrile neutropenia (50.0%) and stomatitis (43.3%). One
transplantation-related death was observed. A combination of dose-targeted i.v.
Bu and bortezomib induced PR or better in one third of patients with MM who
underwent a second autotransplantation, with acceptable toxicity.
PMID- 25139219
TI - Anti-amyloidogenic property of human gastrokine 1.
AB - Gastrokine 1 (GKN1) is a stomach-specific protein expressed in normal gastric
tissue but absent in gastric cancer. GKN1 plays a major role in maintaining
gastric mucosa integrity and is characterized by the presence of a BRICHOS domain
consisting of about 100 amino acids also found in several unrelated proteins
associated with major human diseases like BRI2, related to familial British and
Danish dementia and surfactant protein C (SP-C), associated with respiratory
distress syndrome. It was reported that recombinant BRICHOS domains from BRI2 and
SP-C precursor (proSP-C) prevent fibrils formation of amyloid-beta peptide
(Abeta), that is the major component of extracellular amyloid deposits in
Alzheimer's disease. Here we investigated on the interaction between human
recombinant GKN1 (rGKN1) and Abeta peptide (1-40) that derives from the partial
hydrolysis of the amyloid precursor protein (APP). GKN1 prevented amyloid
aggregation and fibrils formation by inhibiting Abeta(1-40) polymerization, as
evaluated by SDS-PAGE, thioflavin-T binding assay and gel filtration experiments.
Mass spectrometry showed the formation of a prevailing 1:1 complex between GKN1
and Abeta(1-40). SPR analysis of GKN1/Abeta interaction led to calculate a
dissociation constant (KD) of 34 MUM. Besides its interaction with Abeta(1-40),
GKN1 showed also to interact with APP as evaluated by confocal microscopy and Ni
NTA pull-down. Data strongly suggest that GKN1 has anti-amyloidogenic properties
thus functioning as a chaperone directed against unfolded segments and with the
ability to recognize amyloidogenic polypeptides and prevent their aggregation.
PMID- 25139220
TI - Bacterial role in pine wilt disease development - review and future perspectives.
AB - Mutualistic and beneficial relationships between nematodes and bacteria are
highly present in nature, mostly occurring because of nutritional dependence and
pathogen protection, and intrinsically related with the environment, the
ecological conditions and the nematode life stages. Thirty-four years have passed
since the first hypothesis suggesting a bacterial role in pine wilt disease
(PWD), associated with the pinewood nematode (PWN), Bursaphelenchus xylophilus.
In 1980, researchers reported that bacteria associated with the PWN could produce
toxins that lead to PWD development in pine seedlings. It was also suggested a
double vector system for PWD, where bacteria were vectored by the PWN and the PWN
vectored by an insect from the Monochamus genus. Presently, the specific
involvement of bacteria in such complex disease is still controversial, even
though the increased number of studies focused on the potential bacteria role has
increased considerably. This review is an up-to-date comprehensive perspective
and brings new insights on the role of PWN-associated bacteria in PWD.
PMID- 25139221
TI - Residues of deoxynivalenol (DON) and its metabolite de-epoxy-DON in eggs, plasma
and bile of laying hens of different genetic backgrounds.
AB - In the present study, the potential for carry-over of deoxynivalenol (DON) into
eggs and DON residues in plasma and bile of laying hens of different genetic
backgrounds after long-term feeding trial was investigated. A total of 80, 23
week-old laying hens were assigned to a feeding trial with two diets, a control
diet and a Fusarium toxin-contaminated diet (FUS) (0.4 and 9.9 mg DON kg(-1),
respectively). In the 60th week of hen's life, 10 eggs from each group were
collected. In the 70th week of hen's life, all hens were slaughtered and samples
of blood and bile were collected. The samples were analysed by liquid
chromatography tandem mass spectrometry (LC-MS/MS) for DON and de-epoxy-DON. DON
was only detected in samples of hens which fed the FUS diet while none of the
samples analysed had detectable levels of de-epoxy-DON. In plasma and bile
samples, DON levels ranged from 0.2 to 0.6 ng ml(-1) and from 1.8 to 4.1 ng ml(
1), respectively. DON levels in egg yolk and albumen ranged between 0.0-0.46 ng
g(-1) and 0.0-0.35 ng g(-1), respectively, corresponding to carry-over rates of
DON into eggs from 0.0 to 0.000016. Moreover, no differences in DON levels or
carry-over rates were noticed between the two tested breeds. These results show
that very low levels of DON were transferred into eggs and indicate that although
eggs could contribute to human exposure to DON, the levels are very low and
insignificant.
PMID- 25139222
TI - Effects of the volatile anesthetic sevoflurane on tonic GABA currents in the
mouse striatum during postnatal development.
AB - The volatile anesthetic sevoflurane, which is widely used in pediatric surgery,
has proposed effects on GABAA receptor-mediated extrasynaptic tonic inhibition.
In the developing striatum, medium-sized spiny projection neurons have tonic GABA
currents, which function in the excitatory/inhibitory balance and maturation of
striatal neural circuits. In this study, we examined the effects of sevoflurane
on the tonic GABA currents of medium spiny neurons in developing striatal slices.
Sevoflurane strongly increased GABAA receptor-mediated tonic conductance at
postnatal days 3-35. The antagonist of the GABA transporter-1, 1-[2
[[(diphenylmethylene)imino]oxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic
acid hydrochloride further increased tonic GABA conductance during the
application of sevoflurane, thereby increasing the total magnitude of tonic
currents. Both GABA (5 MUM) and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-3-ol
hydrochloride, the delta-subunit-containing GABAA receptor agonist, induced tonic
GABA currents in medium spiny neurons but not in cholinergic neurons. However,
sevoflurane additively potentiated the tonic GABA currents in both cells.
Interestingly, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-3-ol hydrochloride
sensitive neurons made a large current response to sevoflurane, indicating the
contribution of the delta-subunit on sevoflurane-enhanced tonic GABA currents.
Our findings suggest that sevoflurane can affect the tone of tonic GABA
inhibition in a developing striatal neural network.
PMID- 25139223
TI - A safety evaluation of aripiprazole for treating schizophrenia during pregnancy
and puerperium.
AB - INTRODUCTION: Aripiprazole (ARI) is a second-generation antipsychotic acting as a
dopamine-serotonin system stabilizer and partial agonist at D2 receptors. The
drug is indicated in several and severe psychiatric disorders which are
particularly frequent in women during the childbearing age. AREA COVERED: A
systematic review of studies investigating the reproductive safety of ARI. EXPERT
OPINION: For first trimester use, reviewed data provide no clear evidence about
the safety of the drug for the developing fetus. However, a decline of plasma
levels (PLs) throughout the pregnancy compared with PLs before pregnancy was
observed. This finding suggests the need to increase the dosage during pregnancy
in order to maintain stable PLs. If used during late pregnancy, some signals
exist suggesting that ARI may worse neonatal outcomes. Hence, clinicians should
consider withdrawing the drug before the last month of pregnancy to reduce the
risks of neonatal complications. However, such risks must be weighed against the
risks of woman's symptom deterioration. In any case, parturition should happen in
hospitals equipped with well-organized neonatal intensive care units. No
information is available on the impact of antenatal exposure to ARI on the main
neurodevelopmental milestones. Infant exposure to the drug through maternal milk
may increase the risk of insufficient milk production and neonatal somnolence.
PMID- 25139224
TI - Diagnostic laparoscopy with 5-aminolevulinic-acid-mediated photodynamic diagnosis
enhances the detection of peritoneal micrometastases in advanced gastric cancer.
AB - OBJECTS: Recently, we reported that diagnostic laparoscopy with photodynamic
diagnosis using oral 5-aminolevulinic acid (ALA-PDD) is a promising tool for
diagnosing early peritoneal metastases in gastric cancer. The present study
evaluated the usefulness of adding ALA-PDD to conventional diagnostic laparoscopy
and assessed the association of the ALA-PDD results with peritoneal fluid
cytology and molecular diagnostic testing. METHODS: Diagnostic laparoscopy using
sequential white light (WL) and ALA-PDD observations was performed in 52 advanced
gastric cancer patients, and the sensitivity of ALA-PDD for detecting peritoneal
disease was compared to WL. Peritoneal fluid samples from the same patients were
also subjected to cytological examination and molecular diagnosis using a
transcription-reverse transcription concerted reaction (TRC). RESULTS: Twenty
four of the 52 patients (46%) had no macroscopic evidence of peritoneal
metastases on WL examination; however, ALA-PDD detected dissemination in 5 of
these 24 patients (21%) (pd-P). Cytological examination was negative in 4 of the
5 pd-P patients, and molecular testing using TRC was negative in 3 of the 5 pd-P
patients. CONCLUSIONS: This study demonstrated that diagnostic laparoscopy with
ALA-PDD improved the sensitivity for the detection of peritoneal metastases. ALA
PDD may be a useful technique for the preoperative staging of advanced gastric
cancer and can complement examinations of peritoneal lavage fluids.
PMID- 25139225
TI - Blue-colored tert-butylamine clathrate hydrate.
AB - Clathrate hydrates preserve active species more stably than the other icy
materials and investigation of the behavior of the active species elucidates the
physicochemical properties of clathrate hydrates like guest-guest interaction.
Color of the tert-butylamine clathrate hydrate changes to blue after gamma
irradiation and is bleachable with visible light. The electron spin resonance
(ESR) spectrum at 120 K mainly consists of a triplet signal of the C-centered
radical NH2C(CH3)2CH2* together with a single signal at g = 2.0008. The latter
signal disappears after light exposure. These results indicate that both the blue
color and the single ESR signal are derived from trapped electrons in the
hydrate. They thermally decay around 140-160 K by the first-order reaction, and
the activation energy is 27 kJ/mol. Since tert-butylamine molecules can capture
protons due to the high proton affinity, electrons may remain in the hydrate
without reacting with protons, making the hydrate blue after gamma irradiation.
The long-lived trapped electrons in the tert-butylamine hydrate have an advantage
to investigate those in icy materials because tert-butylamine hydrate is nonionic
and has a tetra-coordinated host water network like crystalline ice without any
substitution for water molecules.
PMID- 25139226
TI - Periodontal dressing after surgical crown lengthening: a randomized clinical
trial.
AB - OBJECTIVE: The aim of the present study was to evaluate the effect of periodontal
dressing on post-operative pain and swelling after surgical crown lengthening.
MATERIALS AND METHODS: A blind, randomized, clinical trial was carried out with
36 patients. Following surgical crown lengthening, the individuals were randomly
allocated to the periodontal dressing group (PDG) and control group (CG, non
placement of periodontal dressing). Pain and discomfort were analyzed using a
visual analog scale (VAS), verbal scale (VS) and the number of analgesics
consumed in 7 days post-operatively. Post-operative infection, stability of the
gingival margin and type of healing were also evaluated. RESULTS: The PDG had a
significantly higher percentage of responses of 'strong pain' on the VS in the
first day post-operatively (33.3% vs 5.3%, p = 0.03) and greater pain on the
first and second days post-operatively based on the VAS. Moreover, a significant
difference between groups was found regarding gingival swelling after 7 days.
However, gingival recession was found in 57.8% of the sites in the CG and only
5.5% of sites in the PDG. No change in condition was found among individuals with
conjunctive tissue/bone exposure in the CG in the immediate post-operative period
and 80% of the patients in the PDG had healing by first intention after 7 days.
CONCLUSION: The use of periodontal dressing seems to be preferable following
surgical crown lengthening with connective tissue/bone exposure. However,
adequate post-operative analgesic strategies should be employed due to the
possibility of intense pain in the first 24 hours.
PMID- 25139227
TI - The therapeutic potential of a C-X-C chemokine receptor type 4 (CXCR-4)
antagonist on hypertrophic scarring in vivo.
AB - Effective prevention and treatment of hypertrophic scars (HTSs), a dermal form of
fibrosis that frequently occurs following thermal injury to deep dermis, are
unsolved significant clinical problems. Previously, we have found that stromal
cell-derived factor 1/CXCR4 signaling is up-regulated during wound healing in
burn patients and HTS tissue after thermal injury. We hypothesize that blood
borne mononuclear cells are recruited into wound sites after burn injury through
the chemokine pathway of stromal cell-derived factor 1 and its receptor CXCR4.
Deep dermal injuries to the skin are often accompanied by prolonged inflammation,
which leads to chemotaxis of mononuclear cells into the wounds by chemokine
signaling where fibroblast activation occurs and ultimately HTS are formed.
Blocking mononuclear cell recruitment and fibroblast activation, CXCR4 antagonism
is expected to reduce or minimize scar formation. In this study, the inhibitory
effect of CXCR4 antagonist CTCE-9908 on dermal fibrosis was determined in vivo
using a human HTS-like nude mouse model, in which split-thickness human skin is
transplanted into full-thickness dorsal excisional wounds in athymic mice, where
these wounds subsequently develop fibrotic scars that resemble human HTS as
previously described. CTCE-9908 significantly attenuated scar formation and
contraction, reduced the accumulation of macrophages and myofibroblasts, enhanced
the remodeling of collagen fibers, and down-regulated the gene and protein
expression of fibrotic growth factors in the human skin tissues. These findings
support the potential therapeutic value of CXCR4 antagonist in dermal fibrosis
and possibly other fibroproliferative disorders.
PMID- 25139228
TI - Investigation of age-related differences in an adapted Hayling task.
AB - The Hayling task is traditionally used to assess activation and inhibitory
processes efficiency among various populations, such as elderly adults. However,
the classical design of the task may also involve the influence of strategy use
and efficiency of sentence processing in the possible differences between
individuals. Therefore, the present study investigated activation and inhibitory
processes in aging with two formats of an adapted Hayling task designed to reduce
the involvement of these alternative factors. Thirty young adults (M=20.7 years)
and 31 older adults (M=69.6 years) performed an adapted Hayling task including a
switching block (i.e., unblocked design) in addition to the classical task (i.e.,
blocked design), and the selection of the response between two propositions. The
results obtained with the classical blocked design showed age-related deficits in
the suppression sections of the task but also in the initiation ones. These
findings can be explained by a co-impairment of both inhibition and activation
processes in aging. The results of the unblocked Hayling task, in which strategy
use would be reduced, confirmed this age-related decline in both activation and
inhibition processes. Moreover, significant correlations between the unblocked
design and the Trail Making Test revealed that flexibility is equally involved in
the completion of both sections of this design. Finally, the use of a forced
response choice offers a format that is easy to administer to people with normal
or pathological aging. This seems particularly relevant for these populations in
whom the production of an unrelated word often poses problems.
PMID- 25139229
TI - Arabidopsis thaliana calmodulin-like protein CML24 regulates pollen tube growth
by modulating the actin cytoskeleton and controlling the cytosolic Ca(2+)
concentration.
AB - Cytosolic free calcium ([Ca(2+)]cyt), which is essential during pollen
germination and pollen tube growth, can be sensed by calmodulin-like proteins
(CMLs). The Arabidopsis thaliana genome encodes over 50 CMLs, the physiological
role(s) of most of which are unknown. Here we show that the gene AtCML24 acts as
a regulator of pollen germination and pollen tube extension, since the pollen
produced by loss-of-function mutants germinated less rapidly than that of wild
type (WT) plants, the rate of pollen tube extension was slower, and the final
length of the pollen tube was shorter. The [Ca(2+)]cyt within germinated pollen
and extending pollen tubes produced by the cml24 mutant were higher than their
equivalents in WT plants, and pollen tube extension was less sensitive to changes
in external [K(+)] and [Ca(2+)]. The pollen and pollen tubes produced by cml24
mutants were characterized by a disorganized actin cytoskeleton and lowered
sensitivity to the action of latrunculin B. The observations support an
interaction between CML24 and [Ca(2+)]cyt and an involvement of CML24 in actin
organization, thereby affecting pollen germination and pollen tube elongation.
PMID- 25139232
TI - Genetics of osteoporosis.
AB - Osteoporosis is a skeletal disease characterized by low bone mineral density
(BMD) and microarchitectural deterioration of bone tissue, which increases
susceptibility to fractures. BMD is a complex quantitative trait with normal
distribution and seems to be genetically controlled (in 50-90% of the cases),
according to studies on twins and families. Over the last 20 years, candidate
gene approach and genome-wide association studies (GWAS) have identified single
nucleotide polymorphisms (SNPs) that are associated with low BMD, osteoporosis,
and osteoporotic fractures. These SNPs have been mapped close to or within genes
including those encoding nuclear receptors and WNT-beta-catenin signaling
proteins. Understanding the genetics of osteoporosis will help identify novel
candidates for diagnostic and therapeutic targets.
PMID- 25139230
TI - Seed-specific increased expression of 2S albumin promoter of sesame qualifies it
as a useful genetic tool for fatty acid metabolic engineering and related
transgenic intervention in sesame and other oil seed crops.
AB - The sesame 2S albumin (2Salb) promoter was evaluated for its capacity to express
the reporter gusA gene encoding beta-glucuronidase in transgenic tobacco seeds
relative to the soybean fad3C gene promoter element. Results revealed increased
expression of gusA gene in tobacco seed tissue when driven by sesame 2S albumin
promoter. Prediction based deletion analysis of both the promoter elements
confirmed the necessary cis-acting regulatory elements as well as the minimal
promoter element for optimal expression in each case. The results also revealed
that cis-regulatory elements might have been responsible for high level
expression as well as spatio-temporal regulation of the sesame 2S albumin
promoter. Transgenic over-expression of a fatty acid desaturase (fad3C) gene of
soybean driven by 2S albumin promoter resulted in seed-specific enhanced level of
alpha-linolenic acid in sesame. The present study, for the first time helped to
identify that the sesame 2S albumin promoter is a promising endogenous genetic
element in genetic engineering approaches requiring spatio-temporal regulation of
gene(s) of interest in sesame and can also be useful as a heterologous genetic
element in other important oil seed crop plants in general for which seed oil is
the harvested product. The study also established the feasibility of fatty acid
metabolic engineering strategy undertaken to improve quality of edible seed oil
in sesame using the 2S albumin promoter as regulatory element.
PMID- 25139233
TI - Screening of recombinant Escherichia coli using activation of green fluorescent
protein as an indicator.
AB - A novel cloning vector that can be used to identify recombinant Escherichia coli
colonies by activation of the green fluorescent protein gene (GFP) was
constructed. Screening using the vector does not require special reagents. The
recombinant plasmid activates GFP, and the rate of false-positive results is low.
PMID- 25139231
TI - The pineapple AcMADS1 promoter confers high level expression in tomato and
Arabidopsis flowering and fruiting tissues, but AcMADS1 does not complement the
tomato LeMADS-RIN (rin) mutant.
AB - A previous EST study identified a MADS box transcription factor coding sequence,
AcMADS1, that is strongly induced during non-climacteric pineapple fruit
ripening. Phylogenetic analyses place the AcMADS1 protein in the same superclade
as LeMADS-RIN, a master regulator of fruit ripening upstream of ethylene in
climacteric tomato. LeMADS-RIN has been proposed to be a global ripening
regulator shared among climacteric and non-climacteric species, although few
functional homologs of LeMADS-RIN have been identified in non-climacteric
species. AcMADS1 shares 67 % protein sequence similarity and a similar expression
pattern in ripening fruits as LeMADS-RIN. However, in this study AcMADS1 was not
able to complement the tomato rin mutant phenotype, indicating AcMADS1 may not be
a functionally conserved homolog of LeMADS-RIN or has sufficiently diverged to be
unable to act in the context of the tomato network of interacting proteins. The
AcMADS1 promoter directed strong expression of the GUS reporter gene to fruits
and developing floral organs in tomato and Arabidopsis thaliana, suggesting
AcMADS1 may play a role in flower development as well as fruitlet ripening. The
AcMADS1 promoter provides a useful molecular tool for directing transgene
expression, particularly where up-regulation in developing flowers and fruits is
desirable.
PMID- 25139234
TI - Mammalian target of rapamycin is essential for cardiomyocyte survival and heart
development in mice.
AB - Mammalian target of rapamycin (mTOR) is a critical regulator of protein
synthesis, cell proliferation and energy metabolism. As constitutive knockout of
Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal
development and postnatal growth of heart is not well defined. In this study, we
established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by
crossing MCK-Cre and Mtor(flox/flox) mice. Although the mTOR-mKO mice survived
embryonic and perinatal development, they exhibited severe postnatal growth
retardation, cardiac muscle pathology and premature death. At the cellular level,
the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and
necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac
muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and
glycolysis related genes compared to the WT littermates. In addition, the mTOR
mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating
cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased
the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and
mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR
is essential for cardiomyocyte survival and cardiac muscle function.
PMID- 25139235
TI - WRNIP1 functions upstream of DNA polymerase eta in the UV-induced DNA damage
response.
AB - WRNIP1 (WRN-interacting protein 1) was first identified as a factor that
interacts with WRN, the protein that is defective in Werner syndrome (WS). WRNIP1
associates with DNA polymerase eta (Poleta), but the biological significance of
this interaction remains unknown. In this study, we analyzed the functional
interaction between WRNIP1 and Poleta by generating knockouts of both genes in
DT40 chicken cells. Disruption of WRNIP1 in Poleta-disrupted (POLH(-/-)) cells
suppressed the phenotypes associated with the loss of Poleta: sensitivity to
ultraviolet light (UV), delayed repair of cyclobutane pyrimidine dimers (CPD),
elevated frequency of mutation, elevated levels of UV-induced sister chromatid
exchange (SCE), and reduced rate of fork progression after UV irradiation. These
results suggest that WRNIP1 functions upstream of Poleta in the response to UV
irradiation.
PMID- 25139236
TI - Cellular inhibitor of apoptosis protein 1 ubiquitinates endonuclease G but does
not affect endonuclease G-mediated cell death.
AB - Inhibitors of Apoptosis Proteins (IAPs) are evolutionarily well conserved and
have been recognized as the key negative regulators of apoptosis. Recently, the
role of IAPs as E3 ligases through the Ring domain was revealed. Using proteomic
analysis to explore potential target proteins of DIAP1, we identified Drosophila
Endonuclease G (dEndoG), which is known as an effector of caspase-independent
cell death. In this study, we demonstrate that human EndoG interacts with IAPs,
including human cellular Inhibitor of Apoptosis Protein 1 (cIAP1). EndoG was
ubiquitinated by IAPs in vitro and in human cell lines. Interestingly, cIAP1 was
capable of ubiquitinating EndoG in the presence of wild-type and mutant
Ubiquitin, in which all lysines except K63 were mutated to arginine. cIAP1
expression did not change the half-life of EndoG and cIAP1 depletion did not
alter its levels. Expression of dEndoG 54310, in which the mitochondrial
localization sequence was deleted, led to cell death that could not be suppressed
by DIAP1 in S2 cells. Moreover, EndoG-mediated cell death induced by oxidative
stress in HeLa cells was not affected by cIAP1. Therefore, these results indicate
that IAPs interact and ubiquitinate EndoG via K63-mediated isopeptide linkages
without affecting EndoG levels and EndoG-mediated cell death, suggesting that
EndoG ubiquitination by IAPs may serve as a regulatory signal independent of
proteasomal degradation.
PMID- 25139237
TI - Distribution and baseline values of trace elements in the sediment of Var River
catchment, Southeast France.
AB - This study reports on the determination of trace element (TE)-Li, As, Co, Cs, Cu,
Pb, U, and Zn-and major element (ME)-Si, Al, Fe, Mg, Ca, Mn, Na, and K
concentrations in 18 riverbed sediments and a sediment core from the Var River
catchment using inductively coupled plasma mass spectrometry (ICP-MS). The
results were compared with those of a reference sediment core, and the
contribution of clay and organic carbon contents in the distribution of TE and ME
in the sediment samples was investigated. The mean concentrations of the ME were
comparable in both core and riverbed samples and were within the natural
averages. In the case of TE, the concentrations were lower in riverbed sediment
samples than those found in the sediment core. High mean concentration of As was
observed (7.6 MUg g(-1)) in both core and riverbed sediments, relatively higher
than the worldwide reported values. The obtained data indicated that the natural
high level of arsenic might be originated from the parent rocks, especially
metamorphic rocks surrounding granites and from Permian sediments. Statistical
approach, viz., Pearson correlation matrix, was applied to better understand the
correlation among TE in both riverbed and sediment core samples. No significant
metallic contamination was detected in the low Var valley despite of the
localization of several industrial facilities. Therefore, results confirm that
the concentrations of the TE obtained in the riverbed sediments could be
considered as a baseline guide for future pollution monitoring program.
PMID- 25139238
TI - Soil response to a 3-year increase in temperature and nitrogen deposition
measured in a mature boreal forest using ion-exchange membranes.
AB - The projected increase in atmospheric N deposition and air/soil temperature will
likely affect soil nutrient dynamics in boreal ecosystems. The potential effects
of these changes on soil ion fluxes were studied in a mature balsam fir stand
(Abies balsamea [L.] Mill) in Quebec, Canada that was subjected to 3 years of
experimentally increased soil temperature (+4 degrees C) and increased inorganic
N concentration in artificial precipitation (three times the current N
concentrations using NH4NO3). Soil element fluxes (NO3, NH4, PO4, K, Ca, Mg, SO4,
Al, and Fe) in the organic and upper mineral horizons were monitored using buried
ion-exchange membranes (PRSTM probes). While N additions did not affect soil
element fluxes, 3 years of soil warming increased the cumulative fluxes of K, Mg,
and SO4 in the forest floor by 43, 44, and 79 %, respectively, and Mg, SO4, and
Al in the mineral horizon by 29, 66, and 23 %, respectively. We attribute these
changes to increased rates of soil organic matter decomposition. Significant
interactions of the heating treatment with time were observed for most elements
although no clear seasonal patterns emerged. The increase in soil K and Mg in
heated plots resulted in a significant but small K increase in balsam fir foliage
while no change was observed for Mg. A 6-15 % decrease in foliar Ca content with
soil warming could be related to the increase in soil-available Al in heated
plots, as Al can interfere with the root uptake of Ca.
PMID- 25139240
TI - Applications of time-domain spectroscopy to electron-phonon coupling dynamics at
surfaces.
AB - Photochemistry is one of the most important branches in chemistry to promote and
control chemical reactions. In particular, there has been growing interest in
photoinduced processes at solid surfaces and interfaces with liquids such as
water for developing efficient solar energy conversion. For example, photoinduced
charge transfer between adsorbates and semiconductor substrates at the surfaces
of metal oxides induced by photogenerated holes and electrons is a core process
in photovoltaics and photocatalysis. In these photoinduced processes, electron
phonon coupling plays a central role. This paper describes how time-domain
spectroscopy is applied to elucidate electron-phonon coupling dynamics at metal
and semiconductor surfaces. Because nuclear dynamics induced by electronic
excitation through electron-phonon coupling take place in the femtosecond time
domain, the pump-and-probe method with ultrashort pulses used in time-domain
spectroscopy is a natural choice for elucidating the electron-phonon coupling at
metal and semiconductor surfaces. Starting with a phenomenological theory of
coherent phonons generated by impulsive electronic excitation, this paper
describes a couple of illustrative examples of the applications of linear and
nonlinear time-domain spectroscopy to a simple adsorption system, alkali metal on
Cu(111), and more complex photocatalyst systems.
PMID- 25139239
TI - Identifying fecal pollution sources using 3M(TM) Petrifilm (TM) count plates and
antibiotic resistance analysis in the Horse Creek Watershed in Aiken County, SC
(USA).
AB - Sources of fecal coliform pollution in a small South Carolina (USA) watershed
were identified using inexpensive methods and commonly available equipment.
Samples from the upper reaches of the watershed were analyzed with 3M(TM)
Petrifilm(TM) count plates. We were able to narrow down the study's focus to one
particular tributary, Sand River, that was the major contributor of the coliform
pollution (both fecal and total) to a downstream reservoir that is heavily used
for recreation purposes. Concentrations of total coliforms ranged from 2,400 to
120,333 cfu/100 mL, with sharp increases in coliform counts observed in samples
taken after rain events. Positive correlations between turbidity and fecal
coliform counts suggested a relationship between fecal pollution and stormwater
runoff. Antibiotic resistance analysis (ARA) compared antibiotic resistance
profiles of fecal coliform isolates from the stream to those of a watershed
specific fecal source library (equine, waterfowl, canines, and untreated sewage).
Known fecal source isolates and unknown isolates from the stream were exposed to
six antibiotics at three concentrations each. Discriminant analysis grouped known
isolates with an overall average rate of correct classification (ARCC) of 84.3 %.
A total of 401 isolates from the first stream location were classified as equine
(45.9 %), sewage (39.4 %), waterfowl (6.2 %), and feline (8.5 %). A similar
pattern was observed at the second sampling location, with 42.6 % equine, 45.2 %
sewage, 2.8 % waterfowl, 0.6 % canine, and 8.8 % feline. While there were slight
weather-dependent differences, the vast majority of the coliform pollution in
this stream appeared to be from two sources, equine and sewage. This information
will contribute to better land use decisions and further justify implementation
of low-impact development practices within this urban watershed.
PMID- 25139241
TI - Patient-reported outcomes in long-term survivors of metastatic colorectal cancer
needing liver resection.
AB - BACKGROUND: Five-year survival after hepatic resection for colorectal cancer
(CRC) liver metastases is good, but data on patient-reported outcomes are
lacking. This study describes the long-term impact of liver surgery for CRC
metastases on patient-reported outcomes. METHODS: The study used the European
Organization for Research and Treatment of Cancer (EORTC) Quality of Life
Questionnaire (QLQ) C30 and the disease-specific module, EORTC QLQ-LMC21. For
functional scales, mean scores out of 100 with 95 per cent c.i. were calculated;
differences of 10 points or more were considered clinically significant.
Responses to symptom scales and items were categorized as 'minimal' or 'severe'.
Proportions and 95 per cent c.i. for symptoms were calculated. RESULTS: A total
of 241 patients were recruited; nine (3.7 per cent) had unresectable disease and
were excluded. Some 68 (42 men) of 80 long-term survivors participated; their
mean age was 69.5 years and median follow-up was 8.0 (range 6.9-9.2) years.
Values for baseline and 1-year patient-reported outcome data were similar. Scores
for functional scales were excellent (emotional function: 92, 95 per cent c.i. 87
to 96; social function: 94, 89 to 99; role function: 94, 90 to 98), reflecting
clinically significant improvements from baseline values of 17 (10 to 24), 12 (3
to 21) and 12 (3 to 20) respectively. Severe symptoms were uncommon (affected
less than 5 per cent of patients) for most patient-reported outcome scales or
items, but persistent severe symptoms were noted for sexual function (2 per cent
increase from baseline), peripheral neuropathy (2 per cent increase),
constipation (10 per cent increase) and diarrhoea (5 per cent increase).
CONCLUSION: Long-term survivors of metastatic colorectal cancer who have
undergone liver surgery have excellent global quality of life, high levels of
function and few symptoms.
PMID- 25139242
TI - Changeable naevi in people at high risk for melanoma.
AB - BACKGROUND AND OBJECTIVES: Naevi may change in size, shape and colour due to
multiple inherent and external factors. We observed naevi changing size in adults
at high risk of melanoma, and assessed associations of change with demographic
factors, skin type, sites of naevi and history of melanoma. METHODS: In total, 29
participants with a personal or first-degree family history of melanoma or those
deemed at high risk with multiple naevi of variable morphologies had all
melanocytic naevi 0.5-1 cm imaged and their maximum diameter recorded. Maximum
diameters from repeat imaging of naevi 12 months later were compared to baseline
measurements. Newly appearing naevi >=5 mm and naevi that grew or decreased in
size by 20% or more were defined as changeable naevi. Associations between
changeable naevi and participants' age, sex, skin type, body sites of naevi and
personal and family history of melanoma were assessed. RESULTS: There was no
difference in changeable naevus rates among sex, age or skin type. Among the body
sites, the head and neck were most likely to have changeable naevi, and the upper
limbs the least likely. A family history of melanoma almost tripled the
likelihood of having changeable naevi compared with those without both personal
and family melanoma history. CONCLUSIONS: Naevi can continue to change in size
throughout adulthood, showing both increases and decreases in size as well as the
appearance of new naevi. This has important clinical implications, in particular
for sequential body imaging used for the detection of melanoma.
PMID- 25139243
TI - The functional coupling of the deep abdominal and paraspinal muscles: the effects
of simulated paraspinal muscle contraction on force transfer to the middle and
posterior layer of the thoracolumbar fascia.
AB - The thoracolumbar fascia (TLF) consists of aponeurotic and fascial layers that
interweave the paraspinal and abdominal muscles into a complex matrix stabilizing
the lumbosacral spine. To better understand low back pain, it is essential to
appreciate how these muscles cooperate to influence lumbopelvic stability. This
study tested the following hypotheses: (i) pressure within the TLF's paraspinal
muscular compartment (PMC) alters load transfer between the TLF's posterior and
middle layers (PLF and MLF); and (ii) with increased tension of the common tendon
of the transversus abdominis (CTrA) and internal oblique muscles and incremental
PMC pressure, fascial tension is primarily transferred to the PLF. In cadaveric
axial sections, paraspinal muscles were replaced with inflatable tubes to
simulate paraspinal muscle contraction. At each inflation increment, tension was
created in the CTrA to simulate contraction of the deep abdominal muscles.
Fluoroscopic images and load cells captured changes in the size, shape and
tension of the PMC due to inflation, with and without tension to the CTrA. In the
absence of PMC pressure, increasing tension on the CTrA resulted in anterior and
lateral movement of the PMC. PMC inflation in the absence of tension to the CTrA
resulted in a small increase in the PMC perimeter and a larger posterior
displacement. Combining PMC inflation and tension to the CTrA resulted in an
incremental increase in PLF tension without significantly altering tension in the
MLF. Paraspinal muscle contraction leads to posterior displacement of the PLF.
When expansion is combined with abdominal muscle contraction, the CTrA and
internal oblique transfers tension almost exclusively to the PLF, thereby
girdling the paraspinal muscles. The lateral border of the PMC is restrained from
displacement to maintain integrity. Posterior movement of the PMC represents an
increase of the PLF extension moment arm. Dysfunctional paraspinal muscles would
reduce the posterior displacement of the PLF and increase the compliance of the
lateral border. The resulting change in PMC geometry could diminish any effects
of increased tension of the CTrA. This study reveals a co-dependent mechanism
involving balanced tension between deep abdominal and lumbar spinal muscles,
which are linked through the aponeurotic components of the TLF. This implies the
existence of a point of equal tension between the paraspinal muscles and the
transversus abdominis and internal oblique muscles, acting through the CTrA.
PMID- 25139244
TI - Susceptibility of Escherichia coli to the toxic L-proline analogue L
selenaproline is dependent on two L-cystine transport systems.
AB - AIMS: L-Selenaproline (L-selenazolidine-4-carboxylic acid) is a toxic analogue of
L-proline that inhibits the growth of the urinary tract pathogen Escherichia coli
in both laboratory culture media and normal human urine. The aim of this study
was to identify the transport systems involved in its uptake. METHODS AND
RESULTS: Deletion mutants from the Keio collection were tested for their
susceptibility to L-selenaproline (SCA) and L-selenocystine (SeCys) on minimal
salts agar medium. All single-gene mutants were sensitive to both compounds, but
double mutants with deletions in fliY and ydjN or in yecS and ydjN were resistant
to SCA and SeCys. The YdjN transporter active in strain JW1905 (DeltafliY::kan
yecC(+) yecS(+) ydjN(+)) was inhibited by both SCA and SeCys, but the FliY YecS
YecC ABC transporter system active in strain JW1718 (fliY(+) yecC(+) yecS(+)
DeltaydjN::kan) was best inhibited by these compounds in the presence of
dithiothreitol. CONCLUSIONS: L-selenaproline and L-selenocystine are accumulated
by both the FliY YecC YecS and the YdjN L-cystine transporter systems in E. coli.
SIGNIFICANCE AND IMPACT OF THE STUDY: Because susceptibility to selenium
containing analogues of L-proline and L-cystine is dependent on multiple
transport systems, these compounds may be effective in the treatment of urinary
tract infections.
PMID- 25139245
TI - Pressure mat analysis of naturally occurring lameness in young pigs after
weaning.
AB - BACKGROUND: Lameness is a common problem in modern swine husbandry. It causes
welfare problems in affected pigs as well as financial problems for farmers. To
minimize these negative consequences of lameness, new treatment and prevention
strategies need to be developed and validated using objective and quantitative
measurement techniques. An example of such a putative diagnostic tool is the use
of a pressure mat. Pressure mats are able to provide both objective loading
(kinetic) as well as objective movement (kinematic) information on pig
locomotion.In this study, pressure mat analysis was used to assess compensatory
force redistribution in lame pigs; in particular a predefined set of four
pressure mat parameters was evaluated for its use to objectively distinguish
clinically lame from sound pigs. Kinetic data from 10 clinically lame and 10
healthy weaned piglets were collected. These data were analyzed to answer three
research questions. Firstly the pattern of compensatory weight distribution in
lame animals was studied using the asymmetry indices (ASI) for several
combinations of limbs. Secondly, the correlation between total left-right
asymmetry index and visual scores of lameness was assessed. Thirdly, by using
receiver-operated curve (ROC) analysis, optimal cutoff values for these ASIs were
then calculated to objectively detect lame pigs. RESULTS: Lame animals generally
showed a shift in loading towards their diagonal and contralateral limbs,
resulting in a clear left-right asymmetry. The degree of lameness as graded by
visual scoring correlated well with the total left-right ASIs. Lame pigs could be
objectively distinguished from sound pigs based on clear cutoff points calculated
by ROC analysis for the complete set of four evaluated parameters. CONCLUSIONS:
The gait of lame pigs is asymmetric, due to the unloading of the affected limb
and concomitant weight redistribution towards other limbs. This asymmetry
objectively expressed as total left-right asymmetry, correlates well with the
subjective visual lameness scoring and can be used to objectively distinguish
lame from sound pigs. Pressure mat gait analysis of pigs, therefore, appears to
be a promising and useful tool to objectively quantify and possibly early detect
lameness in pigs.
PMID- 25139246
TI - Retrograde closure of perimembranous ventricular septal defect using muscular
ventricular septal occluder: a single-center experience of a novel technique.
AB - We herein report the advantages of retrograde ventricular septal defect (VSD)
closure using a muscular VSD device for perimembranous VSDs. Perimembranous VSDs
are conventionally closed by an antegrade technique (arteriovenous looping
technique) using a patent ductus arteriosus or asymmetric perimembranous VSD
device. However, we used a symmetrical muscular VSD device in all cases described
in this report. Use of the antegrade technique for the first few patients with
VSD resulted in prolonged procedural and fluoroscopic times and frequent slippage
of the device into the right ventricle. Subsequent use of the retrograde
technique shortened the procedural time and allowed for easier closure of the
perimembranous VSD. We performed retrograde closure of perimembranous VSDs using
a symmetrical muscular VSD device in 130 patients. We obtained a high rate of
successful deployment (88.5%) and a low rate of complications (6.0%). We also
achieved shorter procedural and fluoroscopic times than those associated with the
antegrade technique.
PMID- 25139250
TI - Has the Diagnostic and statistical manual of mental illnesses (fifth edition)
jumped the shark and is it now time for Australia to reconsider reliance on it?
AB - OBJECTIVE: The purpose of this article is to consider whether, in light of the
significant controversy surrounding the Diagnostic and statistical manual of
mental illnesses (fifth edition) (DSM-5), it may be time for Australia to
reconsider the influence of, and its past reliance on, the DSM. Also considered
is whether it is now time, with the imminent publication of the The international
statistical classification of diseases and related health problems (eleventh
edition) (ICD-11), to move to the ICD-11 as the primary instrument for diagnosis
and research in Australia. CONCLUSION: That DSM-5 begins its life in an
unprecedented plethora of criticism, not only from lay people but also from
mental health professionals, which should sound a note of caution for continued
reliance on it in Australia.
PMID- 25139249
TI - Oxidant-free dehydrogenative coupling reactions via hydrogen evolution.
AB - Oxidant-free dehydrogenative coupling reactions: Recently, coupling reactions
have followed a novel strategy for the construction of C==C, C==N, C==P, and S==S
bonds by dehydrogenation without using any extra oxidant, via H2 evolution. These
breakthroughs inspire a new direction in the construction of chemical bonds,
towards more sustainable, highly atom-economical, and environmentally benign
synthetic methods.
PMID- 25139252
TI - Investigation into the structural composition of hydroalcoholic solutions as
basis for the development of multiple suppression pulse sequences for NMR
measurement of alcoholic beverages.
AB - An eight-fold suppression pulse sequence was recently developed to improve
sensitivity in (1) H NMR measurements of alcoholic beverages [Magn. Res. Chem.
2011 (49): 734-739]. To ensure that only one combined hydroxyl peak from water
and ethanol appears in the spectrum, adjustment to a certain range of ethanol
concentrations was required. To explain this observation, the structure of water
ethanol solutions was studied. Hydroalcoholic solutions showed extreme behavior
at 25% vol, 46% vol, and 83% vol ethanol according to (1) H NMR experiments. Near
infrared spectroscopy confirmed the occurrence of four significant compounds
('individual' ethanol and water structures as well as two water-ethanol complexes
of defined composition - 1 : 1 and 1 : 3). The successful multiple suppression
can be achieved for every kind of alcoholic beverage with different alcoholic
strengths, when the final ethanol concentration is adjusted to a range between
25% vol and 46% vol (e.g. using dilution or pure ethanol addition). In this
optimum region, an individual ethanol peak was not detected, because the
'individual' water structure and the 1 : 1 ethanol-water complex predominate. The
nature of molecular association in ethanol-water solutions is essential to
elucidate NMR method development for measurement of alcoholic beverages. The
presented approach can be used to optimize other NMR suppression protocols for
binary water-organic solvent mixtures, where hydrogen bonding plays a dominant
role.
PMID- 25139251
TI - Continuous regional anaesthesia provides effective pain management and reduces
opioid requirement following major lower limb amputation.
AB - OBJECTIVES: Postoperative stump pain after major lower limb amputation is a
significant impediment to the recovery of amputees. The vast majority of patients
require opioid analgesics following surgery, which are associated with opioid
related side-effects. Here, we investigate whether intraoperative placement of a
peripheral nerve stump catheter followed by continuous infusion of local
anesthetic is as effective at pain control as current analgesic practices. If
beneficial, this procedure could potentially reduce post-amputation opioid
consumption and opioid-related adverse effects. METHODS: A retrospective chart
review was conducted of 198 patients over a 4-year period who had undergone a
major lower limb amputation for indications related to peripheral vascular
disease. Postoperatively, 102 patients received a perineural catheter were
compared to 96 patients who did not. The primary outcomes of this study were the
amount of morphine equivalents used in the first 72 hours postoperatively and
postoperative pain intensity in the first 24 hours. RESULTS: A total of 198 lower
limb amputations were selected for analyses. Multiple regression analyses
indicated that perineural catheter use was associated with a lower cumulative
postoperative opioid consumption over the first 72 hours but not postoperative
pain scores at 24 hours. Perineural catheter use led to a 40% reduction in opioid
use during the first 72 hours postoperatively. Mixed model repeated measures
analysis demonstrated that this opioid reduction was consistent over time. Other
variables related to total opioid use included age, pre-surgical chronic pain,
pre-surgical opioid use, patient-controlled analgesia. CONCLUSIONS: Continuous
perineural infusions of local anesthetic are a safe and effective method for
reducing post-amputation opioid analgesic medications after major lower limp
amputation.
PMID- 25139247
TI - Williams-Beuren syndrome: computed tomography imaging review.
AB - Williams-Beuren syndrome (WBS) affects young infants and children. The underlying
etiopathogenesis of this rare disease is due to the mutation of the elastin gene
that is responsible for the elasticity of the arterial wall. As a result of
inadequate elastin production, the major systemic arteries become abnormally
rigid and can be manifested by an impediment to the blood flow. The most common
cardiovascular abnormalities encountered in WBS are supravalvular aortic
stenosis, pulmonary arterial stenosis, and mitral valve prolapse. Less frequently
observed cardiovascular abnormalities include coarctation of the aorta,
ventricular septal defect, patent ductus, subaortic stenosis, and hypertrophic
cardiomyopathy. Coronary artery stenosis and severe impediment to the bi
ventricular outflow as a result of supravalvular aortic and pulmonary artery
stenosis predispose patients to sudden death. Patients with progressed arterial
stenosis and severe stenosis are likely to require intervention to prevent
serious complications. Rarely, imaging findings may precede clinical
presentation, which allows the radiologist to participate in the patient care.
However, to be more prudent, the radiologist must be accustomed to the imaging
characteristics of WBS as well as the patient's clinical information, which could
raise the suspicion of WBS. We performed a retrospective analysis of all the
available images from patients diagnosed with WBS in last 4 years at our
institution, and present key imaging findings along with a review of the
literature to summarize the clinically relevant features as demonstrated by
multidetector computed tomography in WBS. Cross-sectional imaging plays a vital
role in the diagnosis of WBS cases with equivocal clinical features. MDCT
evaluation of complex cardiovascular abnormalities of WBS including coronary
artery disease is feasible with modern MDCT scanners and in the future, this
approach could provide accurate information for planning, navigation, and
noninvasive assessment of the secondary arterial changes in WBS and thus reducing
the dependence upon invasive contrast catherization techniques.
PMID- 25139253
TI - Symptomatic hypercalcemia in a rabies survivor underwent hemodialysis.
AB - Adrenal insufficiency is an uncommon and easily ignored cause among most
etiologies of hypercalcemia because not all cases of adrenal insufficiency
presented with hypercalcemia. In most cases of adrenal insufficiency, viral
encephalitis-related panhypopituitarism is a rare complication that is
sporadically encountered in previous studies. However, this complication has
never been reported in rabies encephalitis because of the extremely high rate of
mortality. Rapid recovery from hypercalcemia state after glucocorticoid
supplement is a direct hint of adrenal insufficiency related hypercalcemia.
PMID- 25139254
TI - Identification of an MLL4-GPS2 fusion as an oncogenic driver of undifferentiated
spindle cell sarcoma in a child.
AB - Undifferentiated spindle cell sarcoma (UDS) is a poorly defined or understood
entity, essentially a waste-basket for cases failing to fulfill criteria for
better-established diagnoses based on combined histology, immunohistochemistry,
and tumor genetic assays. We identified a novel chromosomal translocation
t(17;19)(p13;q13) in a pediatric UDS and have characterized this alteration to
show rearrangement of the MLL4 and GPS2 genes, resulting in an in-frame fusion
gene MLL4-GPS2, the expression of which promotes anchorage-independent growth.
MLL4 was previously reported to be similarly rearranged in hepatocellular
carcinomas, notably those positive for hepatitis B virus. Isolated reports of
individual rearrangements of GPS2 in a prostate carcinoma cell line and in
glioblastoma multiforme, each with different partner genes, recently emerged from
high-throughput sequencing studies but have not been further evaluated for
biological effect.
PMID- 25139255
TI - Dismal outcome of acute myeloid leukemia secondary to myelodysplastic syndrome
and chronic myelomonocytic leukemia after azacitidine failure in a daily-life
setting.
PMID- 25139256
TI - Systematic reviews addressing identified health policy priorities in Eastern
Mediterranean countries: a situational analysis.
AB - BACKGROUND: Systematic reviews can offer policymakers and stakeholders concise,
transparent, and relevant evidence pertaining to pressing policy priorities to
help inform the decision-making process. The production and the use of systematic
reviews are specifically limited in the Eastern Mediterranean region. The extent
to which published systematic reviews address policy priorities in the region is
still unknown. This situational analysis exercise aims at assessing the extent to
which published systematic reviews address policy priorities identified by
policymakers and stakeholders in Eastern Mediterranean region countries. It also
provides an overview about the state of systematic review production in the
region and identifies knowledge gaps. METHODS: We conducted a systematic search
of the Health System Evidence database to identify published systematic reviews
on policy-relevant priorities pertaining to the following themes: human resources
for health, health financing, the role of the non-state sector, and access to
medicine. Priorities were identified from two priority-setting exercises
conducted in the region. We described the distribution of these systematic
reviews across themes, sub-themes, authors' affiliations, and countries where
included primary studies were conducted. RESULTS: Out of the 1,045 systematic
reviews identified in Health System Evidence on selected themes, a total of 200
systematic reviews (19.1%) addressed the priorities from the Eastern
Mediterranean region. The theme with the largest number of systematic reviews
included was human resources for health (115) followed by health financing (33),
access to medicine (27), and role of the non-state sector (25). Authors based in
the region produced only three systematic reviews addressing regional priorities
(1.5%). Furthermore, no systematic review focused on the Eastern Mediterranean
region. Primary studies from the region had limited contribution to systematic
reviews; 17 systematic reviews (8.5%) included primary studies conducted in the
region. CONCLUSIONS: There are still gaps in the production of systematic reviews
addressing policymakers' and stakeholders' priorities in the Eastern
Mediterranean region. Efforts should be directed towards better aligning
systematic review production with policy needs and priorities. Study findings can
inform the agendas of researchers, research institutions, and international
funding agencies of priority areas where systematic reviews are required.
PMID- 25139257
TI - The efficacy of an intervention for the management of postpartum fatigue.
AB - OBJECTIVE: To assess the efficacy of a psychoeducational intervention, Wide Awake
Parenting (WAP), to decrease symptoms of postnatal fatigue. DESIGN: A randomized
controlled trial. SETTING: Local government areas within the Australian state of
Victoria. PARTICIPANTS: Two hundred and two mothers were randomly allocated to
either the professionally-led telephone support intervention (n = 63), self
directed written intervention (n = 67), or waitlist control (n = 72). METHODS:
The professionally-led group received a workbook, home visit, and three telephone
support calls. The self-directed written group received the workbook only, and
the control group received usual health care services. Primary outcomes were
symptoms of fatigue, depression, anxiety and stress, and health care beliefs and
behaviors. Mothers were followed up at 2- and 6-weeks postintervention. RESULTS:
Mothers in the professionally-led group reported fewer symptoms of fatigue than
mothers in the control condition at 6 weeks postintervention. Mothers in either
intervention had more positive attitudes toward their health- and self-care
behaviors at postintervention and follow-up. Mothers in the professionally-led
intervention reported fewer symptoms of depression, anxiety, and stress than
mothers in the other conditions at postintervention. CONCLUSION: Wide Awake
Parenting is effective in promoting mothers' self-efficacy to prioritize, plan
for, and engage in health and self-care behaviors to promote mental health and
manage fatigue. Implications and future opportunities for WAP are discussed.
PMID- 25139258
TI - PARP inhibitor olaparib increases the oncolytic activity of dl922-947 in in vitro
and in vivo model of anaplastic thyroid carcinoma.
AB - PARP inhibitors are mostly effective as anticancer drugs in association with DNA
damaging agents. We have previously shown that the oncolytic adenovirus dl922-947
induces extensive DNA damage, therefore we hypothesized a synergistic antitumoral
effect of the PARP inhibitor olaparib in association with dl922-947. Anaplastic
thyroid carcinoma was chosen as model since it is a particularly aggressive tumor
and, because of its localized growth, it is suitable for intratumoral treatment
with oncolytic viruses. Here, we show that dl922-947 infection induces PARP
activation, and we confirm in vitro and in vivo that PARP inhibition increases
dl922-947 replication and oncolytic activity. In vitro, the combination with
olaparib exacerbates the appearance of cell death markers, such as Annexin V
positivity, caspase 3 cleavage, cytochrome C release and propidium iodide
permeability. In vivo, we also observed a better viral distribution upon PARP
inhibition. Changes in CD31 levels suggest a direct effect of olaparib on tumor
vascularization and on the viral distribution within the tumor mass. The
observation that PARP inhibition enhances the effects of dl922-947 is highly
promising not only for the treatment of anaplastic thyroid carcinoma but, in
general, for the treatment of other tumors that could benefit from the use of
oncolytic viruses.
PMID- 25139261
TI - Surface plasmon enhancement of broadband photoluminescence emission from graphene
oxide.
AB - The photoluminescence (PL) emission studies of both graphene oxide (GO) and
partially reduced graphene oxide (rGO) have been investigated. It has been
observed that GO has broadband emission from the green to near infrared range and
upon reduction rGO shows blue PL emission. The broadband PL emission is due to
the recombination of the electron-hole pair in the sp(2) domain embedded within
the sp(3) matrix. The broadband PL emission also suggests the existence of
various sizes of the sp(2) domain within the same matrix. Furthermore, PL
emission from GO in the presence of an Au metal thin film has been investigated.
It has been observed that the entire broadband emission from GO in the green to
near infrared wavelength region is enhanced significantly at room temperature.
The Au-GO interface exhibits surface plasmon resonance in the visible wavelength
region and is responsible for over 10 fold enhancement in the photoluminescence
at ~2.36 eV. The electrical property measurements on the GO and rGO thin films
suggested that the rGO exhibits significantly higher electrical conductivity
compared to that of the GO thin film. Furthermore, the GO thin film exhibits
semiconducting behaviour. These properties make the material quite suitable for
fabrication of new generation photonic devices.
PMID- 25139259
TI - Evolution of the central sulcus morphology in primates.
AB - The central sulcus (CS) divides the pre- and postcentral gyri along the dorsal
ventral plane of which all motor and sensory functions are topographically
organized. The motor-hand area of the precentral gyrus or KNOB has been described
as the anatomical substrate of the hand in humans. Given the importance of the
hand in primate evolution, here we examine the evolution of the motor-hand area
by comparing the relative size and pattern of cortical folding of the CS surface
area from magnetic resonance images in 131 primates, including Old World monkeys,
apes and humans. We found that humans and great apes have a well-formed motor
hand area that can be seen in the variation in depth of the CS along the dorsal
ventral plane. We further found that great apes have relatively large CS surface
areas compared to Old World monkeys. However, relative to great apes, humans have
a small motor-hand area in terms of both adjusted and absolute surface areas.
PMID- 25139260
TI - Development and scale-up of a commercial fed batch refolding process for an anti
CD22 two chain immunotoxin.
AB - We describe the development and scale-up of a novel two chain immunotoxin
refolding process. This work provides a case study comparing a clinical
manufacturing process and the commercial process developed to replace it. While
the clinical process produced high quality material, it suffered from low yield
and high yield variability. A systematic approach to process development and
understanding led to a number of improvements that were implemented in the
commercial process. These include a shorter inclusion body recovery process,
limiting the formation of an undesired deamidated species and the implementation
of fed batch dilution refolding for increased refold titers. The use of a
combination of urea, arginine and DTT for capture column cleaning restored the
binding capacity of the capture step column and resulted in consistent capture
step yields compared to the clinical process. Scalability is shown with data from
250 L and 950 L scale refolding processes. Compared to the clinical process it
replaces, the commercial process demonstrated a greater than fivefold improvement
in volumetric productivity at the 950 L refolding scale.
PMID- 25139262
TI - A content analysis of weight stigmatization in popular television programming for
adolescents.
AB - OBJECTIVE: This study provides updated information regarding the prevalence and
characteristics of weight stigma in popular adolescent television programming,
using a sample of favorite shows named by diverse adolescents. METHOD:
Participants in a large, population-based study of Minnesota adolescents (N =
2,793, mean age = 14.4) listed their top three favorite television shows. A
coding instrument was developed to analyze randomly selected episodes from the
most popular 10 programs. Weight-stigmatizing incidents were compared across
television show characteristics and characters' gender and weight status.
RESULTS: Half (50%) of the 30 episodes analyzed contained at least one weight
stigmatizing incident. Both youth- and adult-targeted shows contained weight
stigmatizing comments, but the percent of these comments was much higher for
youth-targeted (55.6%) than general audience-targeted shows (8.3%). Male
characters were more likely than females to engage in (72.7% vs. 27.3%), and be
the targets of, weight stigma (63.6% vs. 36.4%), and there was no difference in
the amount of weight stigmatizing directed at average weight females compared to
overweight females. Targets of these instances showed a negative response in only
about one-third of cases, but audience laughter followed 40.9% of cases.
DISCUSSION: The portrayal of weight stigmatization on popular television shows
including targeting women of average weight-sends signals to adolescents about
the wide acceptability of this behavior and the expected response, which may be
harmful. Prevention of weight stigmatization should take a multi-faceted approach
and include the media. Future research should explore the impact that weight
related stigma in television content has on viewers.
PMID- 25139264
TI - The effects of character transposition within and across words in Chinese
reading.
AB - Given the lack of spaces between words in Chinese text, Chinese readers must
parse these characters into words using their word knowledge. In this situation,
are the characters belonging to a single word or to different words understood
via different character-order encoding processes? In this study, we explored the
effects of word boundaries in Chinese text on character-order encoding. We used
four-character words (the one-word condition) and two two-character words (the
two-word condition) as our targets. We embedded the target words into sentences
and then manipulated the previews of the words using the boundary paradigm. The
preview was identical to the target word (identity condition), had the two middle
characters of the target word transposed (TC condition), or had two middle
characters that were different from those in the target word (SC condition).
Fixation durations on the target word in the TC condition were much longer than
those in the identity condition for the two-word condition, but they were not
significantly different for the one-word condition. Furthermore, for the one-word
condition, gaze durations were longer in the SC than in the TC condition, whereas
for the two-word condition, the difference between the TC and SC conditions was
not significant. Word boundaries were found to affect the character-order
encoding in Chinese reading, further suggesting the early occurrence of word
segmentation.
PMID- 25139263
TI - Investigating the thermostability of succinate: quinone oxidoreductase enzymes by
direct electrochemistry at SWNTs-modified electrodes and FTIR spectroscopy.
AB - Succinate: quinone reductases (SQRs) are the enzymes that couple the oxidation of
succinate and the reduction of quinones in the respiratory chain of prokaryotes
and eukaryotes. Herein, we compare the temperature-dependent activity and
structural stability of two SQRs, the first from the mesophilic bacterium
Escherichia coli and the second from the thermophilic bacterium Thermus
thermophilus, using a combined electrochemical and infrared spectroscopy
approach. Direct electron transfer was achieved with full membrane protein
complexes at single-walled carbon nanotube (SWNT)-modified electrodes. The
possible structural factors that contribute to the temperature-dependent activity
of the enzymes and, in particular, to the thermostability of the Thermus
thermophilus SQR are discussed.
PMID- 25139267
TI - Structural basis for the identification of an i-motif tetraplex core with a
parallel-duplex junction as a structural motif in CCG triplet repeats.
AB - CCG triplet repeats can fold into tetraplex structures, which are associated with
the expansion of (CCG)n trinucleotide sequences in certain neurological diseases.
These structures are stabilized by intertwining i-motifs. However, the structural
basis for tetraplex i-motif formation in CCG triplet repeats remains largely
unknown. We report the first crystal structure of a CCG-repeat sequence, which
shows that two dT(CCG)3 A strands can associate to form a tetraplex structure
with an i-motif core containing four C:C(+) pairs flanked by two G:G homopurine
base pairs as a structural motif. The tetraplex core is attached to a short
parallel-stranded duplex. Each hairpin itself contains a central CCG loop in
which the nucleotides are flipped out and stabilized by stacking interactions.
The helical twists between adjacent cytosine residues of this structure in the i
motif core have an average value of 30 degrees , which is greater than those
previously reported for i-motif structures.
PMID- 25139265
TI - 2-(trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate
suppresses osteoclast maturation and bone resorption by targeting macrophage
colony stimulating factor signaling.
AB - 2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)
TEMOSPho], a derivative of an organic chemical identified from a natural product
library, promotes highly efficient megakaryopoiesis. Here, we show that (R)
TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic
origin, as well as blocking the resorptive function of mature osteoclasts. The
inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the
actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a
receptor for macrophage-colony stimulating factor linked to c-Cbl,
phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho
blocked inflammation-induced bone destruction by reducing the numbers of
osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new
class of antiresorptive drugs for the treatment of bone loss associated with
increased osteoclast maturation and activity.
PMID- 25139266
TI - Upregulation of miR-760 and miR-186 is associated with replicative senescence in
human lung fibroblast cells.
AB - We have previously shown that microRNAs (miRNAs) miR-760, miR-186, miR-337-3p,
and miR-216b stimulate premature senescence through protein kinase CK2 (CK2) down
regulation in human colon cancer cells. Here, we examined whether these four
miRNAs are involved in the replicative senescence of human lung fibroblast IMR-90
cells. miR-760 and miR-186 were significantly upregulated in replicatively
senescent IMR-90 cells, and their joint action with both miR-337-3p and miR-216b
was necessary for efficient downregulation of the alpha subunit of CK2 (CK2alpha)
in IMR-90 cells. A mutation in any of the four miRNA-binding sequences within the
CK2alpha 3'-untranslated region (UTR) indicated that all four miRNAs should
simultaneously bind to the target sites for CK2alpha downregulation. The four
miRNAs increased senescence-associated beta-galactosidase (SA-beta-gal) staining,
p53 and p21(Cip1/WAF1) expression, and reactive oxygen species (ROS) production
in proliferating IMR-90 cells. CK2alpha over-expression almost abolished this
event. Taken together, the present results suggest that the upregulation of miR
760 and miR-186 is associated with replicative senescence in human lung
fibroblast cells, and their cooperative action with miR-337-3p and miR-216b may
induce replicative senescence through CK2alpha downregulation-dependent ROS
generation.
PMID- 25139268
TI - Prospective long-term assessment of sedation-related adverse events and patient
satisfaction for upper endoscopy and colonoscopy.
AB - BACKGROUND: Fear of pain and sedation-related adverse events are impediments for
patients to attend endoscopic screening or surveillance programs. OBJECTIVE: To
investigate the long-term effect of different sedation protocols in patients
undergoing screening or surveillance endoscopy. Moreover, motivation of patients
to decline endoscopic procedures was evaluated by focusing on the patient's
satisfaction, fear and pain in relation to type of sedation used. METHODS:
DESIGN: A prospective, double-blind controlled trial data collection was
performed by using a standardized clinical questionnaire followed by a telephone
interview 3-4 weeks after the initial endoscopic procedure. SETTING: The study
was conducted at the Department of Medicine I at the University Hospital of
Erlangen-Nuremberg. Data collection was performed during June 2012 till April
2013. PATIENTS: Overall, 307 patients were prospectively evaluated (44.3% female,
mean age 51 +/- 17.4 years; mean BMI 25.5 +/- 5.7). 247 patients (80.5%) were
outpatients, 60 inpatients (19.5%). INTERVENTIONS: Endoscopic procedures were
divided into five groups: (i) procedures in the upper gastrointestinal tract,
(ii) complete colonoscopies, (iii) ileocolonoscopies, (iv) incomplete
colonoscopies, and (v) other procedures. MAIN OUTCOME MEASUREMENTS: Patient
satisfaction, fear and pain were measured in a structured and standardized
clinical interview using a 6-point numerical rating scale, where 1 was 'very
satisfied/no pain' and 6 was 'very unsatisfied/unsupportable pain'. RESULTS:
Different types of sedation were assessed: propofol in monosedation (6.5%),
combination of propofol + meperidine (41.0%), combination of midazolam +
meperidine (48.5%) and other combinations (3.9%). Patient satisfaction was
significantly reduced regarding fear and pain during the endoscopic procedure (p
= 0.001 and p = 0.0001, respectively). All patients receiving propofol
monosedation indicated significantly less pain in comparison to other sedation
groups (p < 0.0001). Moreover, sedation with midazolam + meperidine increased the
fear during the procedure significantly in comparison to monosedation with
propofol (p = 0.082). Propofol/meperidine in combination and midazolam/meperidine
increased the probability for cardiovascular events in comparison to monosedation
with propofol (p = 0.005; p = 0.039). Finally, we observed significantly lower
doses of propofol when used in monosedation than propofol in combination with
meperidine (p = 0.066). LIMITATION: Single-center study at a tertiary referral
center. CONCLUSIONS: Propofol in monosedation should preferably be used for
patient sedation in screening and surveillance endoscopies. Whether this approach
could also improve participation rates in screening and surveillance endoscopies
requires further investigations.
PMID- 25139270
TI - Metabolism: sugar on the brain.
PMID- 25139269
TI - Endovascular Management of Cavernous Internal Carotid Artery Pseudoaneurysms
Following Transsphenoidal Surgery: A Report of Two Cases and Review of the
Literature.
PMID- 25139273
TI - Oscillations: a dynamic role for astrocytes.
PMID- 25139276
TI - Evidence for a radial strain gradient in apple fruit cuticles.
AB - MAIN CONCLUSION: The morphological outer side of the apple fruit cuticle is
markedly more strained than the inner side. This strain is released upon wax
extraction. This paper investigates the effect of ablating outer and inner
surfaces of isolated cuticular membranes (CM) of mature apple (Malus * domestica)
fruit using cold atmospheric pressure plasma (CAPP) on the release of strain
after extraction of waxes. Strain release was quantified as the decrease in area
of CM discs following CAPP treatment and subsequent solvent extraction of wax.
Increasing duration of CAPP treatment proportionally decreased CM mass per unit
area. There was no difference in mass loss rate between CAPP treatments of outer
or inner surfaces. Also, there was no difference in surface area of CMs before
and after CAPP treatment. However, upon subsequent wax extraction, surface area
of CMs decreased indicating the release of strain. Increasing the duration of
CAPP treatment resulted in increasing strain release up to 47.7 +/- 8.0 % at 20
min when CAPP was applied to the inner surface. In contrast, strain release was
independent of CAPP duration averaging about 12.1 +/- 0.6 % when applied to the
outer surface of the CM. Our results provide evidence for a marked gradient of
strain between the outer side (strained) and the inner side of the CM (not
strained) of mature apple fruit.
PMID- 25139278
TI - Having a promising efficacy on type II diabetes, it's definitely a green tea
time.
AB - The beneficial effects of green tea have been confirmed in various diseases, such
as different types of cancer, heart disease, and liver disease. The effective
components of green tea mainly include tea polysaccharides and tea polyphenols,
such as catechin, particularly (-)-epigallocatechin-3-gallate. Increasing in vivo
and in vitro evidences have explored the potential molecular mechanisms of green
tea as well as the specific biological actions. Moreover, clinical trials have
also explored the potential value of green tea components in treating metabolic
syndromes, such as obesity, type II diabetes, and cardiovascular disease. This
study explores the effects of the two major green tea components on the
improvement of type II diabetes. It is concluded that regular consumption of
green tea is beneficial for the improvement of high-fat dietary-induced obesity
and type II diabetes.
PMID- 25139277
TI - Regulatory control of carotenoid accumulation in winter squash during storage.
AB - MAIN CONCLUSION: Storage promotes carotenoid accumulation and converts
amylochromoplasts into chromoplasts in winter squash. Such carotenoid enhancement
is likely due to continuous biosynthesis along with reduced turnover and/or
enhanced sequestration. Postharvest storage of fruits and vegetables is often
required and frequently results in nutritional quality change. In this study, we
investigated carotenoid storage plastids, carotenoid content, and its regulation
during 3-month storage of winter squash butternut fruits. We showed that storage
improved visual appearance of fruit flesh color from light to dark orange, and
promoted continuous accumulation of carotenoids during the first 2-month storage.
Such an increased carotenoid accumulation was found to be concomitant with starch
breakdown, resulting in the conversion of amylochromoplasts into chromoplasts.
The butternut fruits contained predominantly beta-carotene, lutein, and
violaxanthin. Increased ratios of beta-carotene and violaxanthin to total
carotenoids were noticed during the storage. Analysis of carotenoid metabolic
gene expression and PSY protein level revealed a decreased expression of
carotenogenic genes and PSY protein following the storage, indicating that the
increased carotenoid level might not be due to increased biosynthesis. Instead,
the increase likely resulted from a continuous biosynthesis with a possibly
reduced turnover and/or enhanced sequestration, suggesting a complex regulation
of carotenoid accumulation during fruit storage. This study provides important
information to our understanding of carotenogenesis and its regulation during
postharvest storage of fruits.
PMID- 25139279
TI - In vivo evaluation of thiolated chitosan tablets for oral insulin delivery.
AB - Chitosan-6-mercaptonicotinic acid (chitosan-6-MNA) is a thiolated chitosan with
strong mucoadhesive properties and a pH-independent reactivity. This study aimed
to evaluate the in vivo potential for the oral delivery of insulin. The
comparison of the nonconjugated chitosan and chitosan-6-MNA was performed on
several studies such as mucoadhesion, release, and in vivo studies. Thiolated
chitosan formulations were both about 80-fold more mucoadhesive compared with
unmodified ones. The thiolated chitosan tablets showed a sustained release for 5
h for the polymer of 20 kDa and 8 h for the polymer of 400 kDa. Human insulin was
quantified in rats' plasma by means of ELISA specific for human insulin with no
cross-reactivity with the endogenous insulin. In vivo results showed thiolation
having a tremendous impact on the absorption of insulin. The absolute
bioavailabilities were 0.73% for chitosan-6-MNA of 20 kDa and 0.62% for chitosan
6-MNA 400 kDa. The areas under the concentration-time curves (AUC) of chitosan-6
MNA formulations compared with unmodified chitosan were 4.8-fold improved for the
polymer of 20 kDa and 21.02-fold improved for the polymer of 400 kDa. The
improvement in the AUC with regard to the most promising aliphatic thiomer was up
to 6.8-fold. Therefore, chitosan-6-MNA represents a promising excipient for the
oral delivery of insulin.
PMID- 25139280
TI - alpha-Synuclein Misfolding Versus Aggregation Relevance to Parkinson's Disease:
Critical Assessment and Modeling.
AB - alpha-Synuclein, an abundant and conserved presynaptic brain protein, is
implicated as a critical factor in Parkinson's disease (PD). The aggregation of
alpha-synuclein is believed to be a critical event in the disease process. alpha
Synuclein is characterized by a remarkable conformational plasticity, adopting
different conformations depending on the environment. Therefore, it is classified
as an "intrinsically disordered protein." Recently, a debate has challenged the
view on the intrinsically disordered behavior of alpha-synuclein in the cell. It
has been proposed that alpha-synuclein is a stable tetramer with a low propensity
for aggregation; however, its destabilization leads to protein misfolding and its
aggregation kinetics. In our critical analysis, we discussed about major issues:
(i) why alpha-synuclein conformational behavior does not fit into the normal
secondary structural characteristics of proteins, (ii) potential amino acids
involved in the complexity of misfolding in alpha-synuclein that leads to
aggregation, and (iii) the role of metals in misfolding and aggregation. To
evaluate the above critical issues, we developed bioinformatics models related to
secondary and tertiary conformations, Ramachandran plot, free energy change,
intrinsic disordered prediction, solvent accessibility, and FoldIndex pattern. To
the best of our knowledge, this is a novel critical assessment to understand the
misfolding biology of synuclein and its relevance to Parkinson's disease.
PMID- 25139283
TI - A partial differential equation for pseudocontact shift.
AB - It is demonstrated that pseudocontact shift (PCS), viewed as a scalar or a tensor
field in three dimensions, obeys an elliptic partial differential equation with a
source term that depends on the Hessian of the unpaired electron probability
density. The equation enables straightforward PCS prediction and analysis in
systems with delocalized unpaired electrons, particularly for the nuclei located
in their immediate vicinity. It is also shown that the probability density of the
unpaired electron may be extracted, using a regularization procedure, from PCS
data.
PMID- 25139282
TI - The Antidepressant-Like Effect of Fish Oil: Possible Role of Ventral Hippocampal
5-HT1A Post-synaptic Receptor.
AB - The pathophysiology of depression is not completely understood; nonetheless,
numerous studies point to serotonergic dysfunction as a possible cause.
Supplementation with fish oil rich docosahexaenoic (DHA) and eicosapentaenoic
acids (EPA) during critical periods of development produces antidepressant
effects by increasing serotonergic neurotransmission, particularly in the
hippocampus. In a previous study, the involvement of 5-HT1A receptors was
demonstrated and we hypothesized that fish oil supplementation (from conception
to weaning) alters the function of post-synaptic hippocampal 5-HT1A receptors. To
test this hypothesis, female rats were supplemented with fish oil during
habituation, mating, gestation, and lactation. The adult male offspring was
maintained without supplementation until 3 months of age, when they were
subjected to the modified forced swimming test (MFST) after infusion of vehicle
or the selective 5-HT1A antagonist, WAY100635, and frequency of swimming,
immobility, and climbing was recorded for 5 min. After the behavioral test, the
hippocampi were obtained for quantification of serotonin (5-HT) and its
metabolite, 5-hydroxyindoleacetic acid (5-HIAA) and for 5-HT1A receptor
expression by Western blotting analysis. Fish oil-supplemented offspring
displayed less depressive-like behaviors in the MFST reflected by decreased
immobility and increased swimming and higher 5-HT hippocampal levels. Although
there was no difference in the expression of hippocampal 5-HT1A receptors, intra
hippocampal infusion of a sub-effective dose of 8-OH-DPAT enhanced the
antidepressant effect of fish oil in supplemented animals. In summary, the
present findings suggest that the antidepressant-like effects of fish oil
supplementation are likely related to increased hippocampal serotonergic
neurotransmission and sensitization of hippocampal 5-HT1A receptors.
PMID- 25139286
TI - Hexavalent chromium reduction in contaminated soil: A comparison between ferrous
sulphate and nanoscale zero-valent iron.
AB - Iron sulphate (FeSO4) and colloidal nano zero-valent iron (nZVI) as reducing
agents were compared, with the aim of assessing their effectiveness in hexavalent
chromium [Cr(VI)] removal from a contaminated industrial soil. Experiments were
performed on soil samples collected from an industrial site where a nickel
contamination, caused by a long-term productive activity, was also verified. The
influence of reducing agents amount with respect to chromium content and the
effectiveness of deoxygenation of the slurry were discussed. The soil was fully
characterized before and after each test, and sequential extractions were
performed to assess chemico-physical modifications and evaluate metals mobility
induced by washing. Results show that both the reducing agents successfully
lowered the amount of Cr(VI) in the soil below the threshold allowed by Italian
Environmental Regulation for industrial reuse. Cr(VI) reduction by colloidal nZVI
proved to be faster and more effective: the civil reuse of soil [Cr(VI)<2mg/kg]
was only achieved using colloidal nZVI within 60min adopting a nZVI/Cr(VI) molar
ratio of 30. The reducing treatment resulted in an increase in the amount of
chromium in the oxide-hydroxide fraction, thus confirming a mechanism of chromium
iron hydroxides precipitation. In addition, a decrease of nickel (Ni) and lead
(Pb) content in soil was also observed when acidic conditions were established.
PMID- 25139285
TI - Urgent lung transplant programme in Italy: analysis of the first 14 months.
AB - OBJECTIVES: Lung transplantation (LTx) is the only effective treatment for end
stage lung disease. In rapidly deteriorating patients awaiting transplant,
supportive strategies for lung function allow only a short period of support and
lung transplantation remains the definitive therapy. An urgent transplant
programme may reduce the waiting time, allowing lung transplantation in these
patients. METHODS: Since November 2010 a nation-wide urgent lung transplant
programme has been established in Italy and patients on the waiting list
dependent on mechanical ventilation and/or extracorporeal lung support (ECLS) can
be transplanted on an emergency basis with the first available graft in the
country. Results of the first 14 months of this programme are analysed here.
RESULTS: From November 2010 to December 2011, 28 patients (14 males, mean age
33.6 +/- 14.4 years) were considered for urgent LTx. Rapidly deteriorating lung
function was supported with mechanical ventilation alone in 4 patients (14.3%),
ECLS in 13 patients (46.4%) and mechanical ventilation plus ECLS in the remaining
11 patients (39.3%). Three patients (10.7%) were excluded because of worsening
conditions, 3 patients (10.7%) while on the urgent listed and 22 patients (78.6%)
underwent transplantation after 9.8 +/- 6.2 days of being on the urgent list. The
30-day mortality rate after LTx was 18%, and the 1-year survival rate was 71.4%.
CONCLUSIONS: The urgent lung transplant programme allowed transplantation in a
significant percentage of prioritized patients with acceptable 30-day and 1-year
mortality rates. An accurate selection of recipients may further improve the
clinical impact of this programme, reducing the ethical concerns about
transplantation in high-risk patients.
PMID- 25139281
TI - Updated findings of the association and functional studies of DRD2/ANKK1 variants
with addictions.
AB - Both nicotine and alcohol addictions are severe public health hazards worldwide.
Various twin and family studies have demonstrated that genetic factors contribute
to vulnerability to these addictions; however, the susceptibility genes and the
variants underlying them remain largely unknown. Of susceptibility genes
investigated for addictions, DRD2 has received much attention. Considering new
evidence supporting the association of DRD2 and its adjacent gene ankyrin repeat
and kinase domain containing 1 (ANKK1) with various addictions, in this paper, we
provide an updated view of the involvement of variants in DRD2 and ANKK1 in the
etiology of nicotine dependence (ND) and alcohol dependence (AD) based on
linkage, association, and molecular studies. This evidence shows that both genes
are significantly associated with addictions; however the association with ANKK1
appears to be stronger. Thus, both more replication studies in independent
samples and functional studies of some of these variants are warranted.
PMID- 25139287
TI - The role of telomeres and telomerase in hematologic malignancies and
hematopoietic stem cell transplantation.
AB - Telomeres are specific nucleoprotein structures at the ends of eukaryotic
chromosomes. Telomeres and telomere-associated proteins maintain genome stability
by protecting the ends of chromosomes from fusion and degradation. In normal
somatic cells, the length of the telomeres gradually becomes shortened with cell
division. In tumor cells, the shortening of telomeres length is accelerated under
the increased proliferation pressure. However, it will be maintained at an
extremely short length as the result of activation of telomerase. Significantly
shortened telomeres, activation of telomerase, and altered expression of telomere
associated proteins are common features of various hematologic malignancies and
are related with progression or chemotherapy resistance in these diseases. In
patients who have received hematopoietic stem cell transplantation (HSCT), the
telomere length and the telomerase activity of the engrafted donor cells have a
significant influence on HSCT outcomes. Transplantation-related factors should be
taken into consideration because of their impacts on telomere homeostasis. As
activation of telomerase is widespread in tumor cells, it has been employed as a
target point in the treatment of neoplastic hematologic disorders. In this
review, the characteristics and roles of telomeres and telomerase both in
hematologic malignancies and in HSCT will be summarized. The current status of
telomerase-targeted therapies utilized in the treatment of hematologic
malignancies will also be reviewed.
PMID- 25139288
TI - Comparative evaluation of molar distalization therapy with erupted second molar:
Segmented versus Quad Pendulum appliance.
AB - BACKGROUND: There are controversial opinions about the effect of erupted second
molars on distalization of the first molars. Most of the distalizing devices are
anchored on the first molars, without including second molars; so, differences
between sequentially distalize maxillary molars (second molar followed by the
first molar) or distalize second and first molars together are not clear. The aim
of the study was to compare sequential versus simultaneous molar distalization
therapy with erupted second molar using two different modified Pendulum
appliances followed by fixed appliances. METHODS: The treatment sample consisted
of 35 class II malocclusion subjects, divided in two groups: group 1 consisted of
24 patients (13 males and 11 females) with a mean pre-treatment age of 12.9
years, treated with the Segmented Pendulum (SP) and fixed appliances; group 2
consisted of 11 patients (6 males and 5 females) with a mean pre-treatment age of
13.2 years, treated with the Quad Pendulum (QP) and fixed appliances. Lateral
cephalograms were obtained before treatment (T1), at the end of distalization
(T2), and at the end of orthodontic fixed appliance therapy (T3). A Student t
test was used to identify significant between-group differences between T1 to T2,
T2 to T3, and T1 to T3. RESULTS: QP and SP were equally effective in distalizing
maxillary molars (3.5 and 4 mm, respectively) between T1 and T2; however, the
maxillary first molar showed less distal tipping (4.6 degrees vs. 9.6 degrees )
and more extrusion (1.1 vs. 0.2 mm) in the QP group than in the SP group, as well
as the vertical facial dimension, which increased more in the QP group (1.2
degrees ) than in the SP group (0.7 degrees ). At T3, the QP group maintained
greater increase in lower anterior facial height and molar extrusion and decrease
in overbite than the SP group. CONCLUSION: Quad Pendulum seems to have greater
increase in vertical dimension and molar extrusion than the Segmented Pendulum.
PMID- 25139289
TI - NK cells kill mycobacteria directly by releasing perforin and granulysin.
AB - Although the mechanisms underlying the cytotoxic effect of NK cells on tumor
cells and intracellular bacteria have been studied extensively, it remains
unclear how these cells kill extracellular bacterial pathogens. In this study, we
examine how human NK cells kill Mycobacterium kansasii and M.tb. The underlying
mechanism is contact dependent and requires two cytolytic proteins: perforin and
granulysin. Mycobacteria induce enhanced expression of the cytolytic proteins via
activation of the NKG2D/NCR cell-surface receptors and intracellular signaling
pathways involving ERK, JNK, and p38 MAPKs. These results suggest that NK cells
use similar cellular mechanisms to kill both bacterial pathogens and target host
cells. This report reveals a novel role for NK cells, perforin, and granulysin in
killing mycobacteria and highlights a potential alternative defense mechanism
that the immune system can use against mycobacterial infection.
PMID- 25139291
TI - Effects of surface wettability on gecko adhesion underwater.
AB - Recent experiments have shown that gecko adhesion underwater depends
significantly on surface wettability. Theoretical models of a gecko seta adhering
on different substrates are firstly established in order to disclose such an
adhesion mechanism. The results show that the capillary force induced by nano
bubbles between gecko seta and the substrate is the mainly influencing factor.
The capillary force exhibits an attractive feature between gecko setae and
hydrophobic surfaces underwater. However, it is extremely weak or even repulsive
on hydrophilic surfaces underwater. A self-similarly splitting model is further
considered to simulate multiple gecko setae on substrates underwater. It is
interesting to find that the total capillary force depends significantly on the
number of nano-bubble bridges and wettability of substrates. The total force is
attractive and increases monotonically with the increase of the splitting number
on hydrophobic substrates underwater. However, it decreases drastically or even
becomes repulsive on hydrophilic substrates underwater. The present result can
not only give a reasonable explanation on the existing experimental observations
but also be helpful for the design of novel biomimetic adhesives.
PMID- 25139290
TI - The mucosal expression pattern of interferon-epsilon in rhesus macaques.
AB - Type I IFNs play an important role in innate and adaptive immunity against viral
infections. A novel type I IFN, namely IFN-epsilon, which can protect against
vaginal transmission of HSV2 and Chlamydia muridarum bacterial infection, has
been described in mice and humans. Nevertheless, the principle cell type and the
expression pattern of IFN-epsilon in tissues remain uncertain. In addition, the
expression of IFN-epsilon in Indian rhesus macaques (Macaca mulatta) has not been
reported. Here, we analyzed IFN-epsilon expression in multiple mucosal sites of
uninfected or SIV-infected Indian rhesus macaques using IHCS. We report for the
first time the detection of IFN-epsilon expression in situ in the lung, foreskin,
vaginal, cervical, and small and large intestinal mucosae of rhesus macaques. We
found that the expression of IFN-epsilon was exclusive to the epithelial cells in
all of the aforementioned mucosal tissues. Furthermore, the macaque IFN-epsilon
sequence in this study revealed that macaque IFN-epsilon is highly conserved
among human and other nonhuman primates. Lastly, SIV rectal infection did not
significantly alter the expression of IFN-epsilon in rectal mucosae. Together,
these findings indicate that IFN-epsilon may function as the first line of
defense against the invasion of mucosal pathogens. Further studies should be
conducted to examine IFN-epsilon protection against gastrointestinal as well as
respiratory infections.
PMID- 25139292
TI - In vivo penetration of bare and lipid-coated silica nanoparticles across the
human stratum corneum.
AB - Skin penetration of silica nanoparticles (NP) currently used in pharmaceutical
and cosmetic products is a topic of interest not only to evaluate their possible
toxicity, but also to understand their behaviour upon contact with the skin and
to exploit their potential positive effects in drug or cosmetic delivery field.
Therefore, the present work aimed to elucidate the in vivo mechanism by which
amorphous hydrophilic silica NP enter human stratum corneum (SC) through the
evaluation of the role played by the nanoparticle surface polarity and the human
hair follicle density. Two silica samples, bare hydrophilic silica (B-silica,
162+/-51nm in size) and hydrophobic lipid-coated silica (LC-silica, 363+/-74nm in
size) were applied on both the volar and dorsal side of volunteer forearms.
Twelve repetitive stripped tapes were removed from the human skin and evaluated
for elemental composition by Energy Dispersive X-ray (EDX) analysis and for
silicon content by Inductively Coupled Plasma quadrupole Mass Spectrometry (ICP
MS). All the stripped tapes revealed nanosized structures generally located in
the broad spaces between corneocytes and characterized by the same elemental
composition (relative weight percentage of silicon and silicon to oxygen weight
ratio) than that of the applied samples. However, only about 10% B-silica
permeated until the deepest SC layers considered in the study indicating a silica
retention in the upper layers of SC, regardless of the hair follicle density.
Otherwise, the exposure to LC-silica led to a greater silica skin penetration
extent into the deeper SC layers (about 42% and 18% silica following volar and
dorsal forearm application, respectively) indicating that the NP surface polarity
played a predominant role on that of their size in determining the route and the
extent of penetration.
PMID- 25139293
TI - A simple and effective approach for the treatment of dyslipidemia using anionic
nanoliposomes.
AB - The present study was undertaken to evaluate the anti-dyslipidemic effects of
nanoliposomes with different phospholipid compositions. Three sets of liposomal
formulations (20Mm; 100nM in size) were prepared with low (SPC), medium (POPC)
and high (HSPC) phase transition temperature values with and without cholesterol
and anionic phosphatidyl glycerol (HSPC/DSPG; POPC/DMPG; SPC/EPG). The liposomal
preparations were characterized for their size and zeta potential (dynamic light
scattering), J774A.1 macrophages uptake (flow cytometry) and lipid-modifying
effects (tyloxapol-induced hyperlipidemic mouse model). Anionic formulations
displayed the highest rate of uptake by macrophages. Among them, HSPC/DSPG and
SPC/EPG liposomes had the best lipid-modifying activity. These two formulations
exerted favorable impact on all lipid profile parameters by reducing LDL-C (by up
to 76% [HSPC/DSPG] and 86% [SPC/EPG]), total cholesterol (by up to 52%
[HSPC/DSPG] and 68% [SPC/EPG]), triglycerides (by up to 88% [HSPC/DSPG] and 73%
[SPC/EPG]), apoB (by up to 44% [HSPC/DSPG] and 35% [SPC/EPG]) and elevating HDL-C
(by up to 85% [HSPC/DSPG] and 75% [SPC/EPG]) concentrations. Atherogenic indices
were also effectively reduced following HSPC/DSPG (by up to 69%) and SPC/EPG (by
up to 79%) injections. Empty, cholesterol-free nanoliposomal formulations
containing 75% anionic phospholipid (PG) might serve as effective and rapid
acting anti-dyslipidemic agents. Further research is warranted to confirm the
observed anti-dyslipidemic effects of anionic nanoliposomes in diet-induced
hyperlipidemic models, and also to evaluate the potential protective effects in
regressing atheromatous lesions.
PMID- 25139294
TI - Biomarkers for personalizing omega-3 fatty acid dosing.
AB - Prostaglandin E2 (PGE2) has been linked to a higher risk of colorectal cancer.
PGE2 in colon tissue can be reduced by increasing dietary eicosapentaenoic acid
(EPA). The dose-dependent relationships between dietary EPA, serum
EPA:arachidonate (AA) ratio, urinary PGE2 metabolites, and colonic eicosanoids
were evaluated to develop biomarkers for prediction of colonic PGE2. Male rats
were fed diets containing EPA:omega6 fatty acid ratios of 0, 0.1, 0.2, 0.4, or
0.6 for 5 weeks. Increasing the dietary EPA:omega6 fatty acid ratio increased
EPA:AA ratios in serum and in the proximal, transverse, and distal colon (P <
0.001). The urinary PGE2 metabolite was reduced (P = 0.006). EPA-rich diets
reduced colonic tissue PGE2 concentrations by 58% to 66% and increased PGE3 by 19
to 28-fold. Other AA-derived eicosanoids were reduced by 35% to 83%. The changes
were not linear, with the largest changes in eicosanoids observed with the lower
doses. A mathematical model predicts colonic tissue eicosanoids from the EPA:AA
ratio in serum and the EPA dose. Every 10% increase in serum EPA:AA was
associated with a 2% decrease in the (geometric) mean of PGE2 in the distal
colon. These mathematical relationships can now be applied to individualized EPA
dosing in clinical trials.
PMID- 25139295
TI - Widefield optical imaging of changes in uptake of glucose and tissue
extracellular pH in head and neck cancer.
AB - The overall objective of this study was to develop an optical imaging approach to
simultaneously measure altered cell metabolism and changes in tissue
extracellular pH with the progression of cancer using clinically isolated
biopsies. In this study, 19 pairs of clinically normal and abnormal biopsies were
obtained from consenting patients with head and neck cancer at University of
California, Davis Medical Center. Fluorescence intensity of tissue biopsies
before and after topical delivery of 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4
yl)amino]-2-deoxy-D-glucose) and Alexa 647-pHLIP [pH (low) insertion peptide] was
measured noninvasively by widefield imaging, and correlated with pathologic
diagnosis. The results of widefield imaging of clinical biopsies demonstrated
that 2-NBDG and pHLIP peptide can accurately distinguish the pathologically
normal and abnormal biopsies. The results also demonstrated the potential of this
approach to detect subepithelial lesions. Topical application of the contrast
agents generated a significant increase in fluorescence contrast (3- to 4-fold)
in the cancer biopsies as compared with the normal biopsies, irrespective of the
patient and location of the biopsy within a head and neck cavity. This unpaired
comparison across all the patients with cancer in this study highlights the
specificity of the imaging approach. Furthermore, the results of this study
indicated that changes in intracellular glucose metabolism and cancer acidosis
are initiated in the early stages of cancer, and these changes are correlated
with the progression of the disease. In conclusion, this novel optical molecular
imaging approach to measure multiple biomarkers in cancer has a significant
potential to be a useful tool for improving early detection and prognostic
evaluation of oral neoplasia.
PMID- 25139296
TI - Analysis of DNA methylation in bowel lavage fluid for detection of colorectal
cancer.
AB - Aberrant DNA methylation could potentially serve as a biomarker for colorectal
neoplasms. In this study, we assessed the feasibility of using DNA methylation
detected in bowel lavage fluid (BLF) for colorectal cancer screening. A total of
508 BLF specimens were collected from patients with colorectal cancer (n = 56),
advanced adenoma (n = 53), minor polyp (n = 209), and healthy individuals (n =
190) undergoing colonoscopy. Methylation of 15 genes (miR-1-1, miR-9-1, miR-9-3,
miR-34b/c, miR-124-1, miR-124-2, miR-124-3, miR-137, SFRP1, SFRP2, APC, DKK2,
WIF1, LOC386758, and ZNF582) was then analyzed in MethyLight assays, after which
receiver operating characteristic (ROC) curves were analyzed to assess the
diagnostic performance of BLF methylation. Through analyzing BLF specimens in a
training set (n = 345), we selected the three genes showing the greatest
sensitivity for colorectal cancer detection (miR-124-3, 71.8%; LOC386758, 79.5%;
and SFRP1, 74.4%). A scoring system based on the methylation of those three genes
(M-score) achieved 82% sensitivity and 79% specificity, and the area under the
ROC curve (AUC) was 0.834. The strong performance of this system was then
validated in an independent test set (n = 153; AUC = 0.808). No significant
correlation was found between M-score and the clinicopathologic features of the
colorectal cancers. Our results demonstrate that DNA methylation in BLF specimens
may be a useful biomarker for the detection of colorectal cancer.
PMID- 25139297
TI - Comparative analysis of gender-related differences in symptoms and referral
patterns prior to initial diagnosis of urothelial carcinoma of the bladder: a
prospective cohort study.
AB - OBJECTIVE: To analyze gender-specific differences regarding clinical symptoms,
referral patterns and tumor biology prior to initial diagnosis of urothelial
carcinoma of the bladder (UCB). METHODS: A consecutive series of patients with an
initial diagnosis of UCB was included. All patients completed a questionnaire on
demographics, clinical symptoms and referral patterns. RESULTS: In total, 68
patients (50 men, 18 women) with newly diagnosed UCB at admission for
transurethral resection of bladder tumors were recruited. Dysuria was more often
observed in women (55.6 vs. 38.0%, p = 0.001). Direct consultation of the
urologist was conducted by 84.0% of males and 66.7% of females (p = 0.120). One
third of the women saw their general practitioner and/or gynecologist once or
twice (p = 0.120) before referral to the urologist. Furthermore, women were
significantly more often treated for urinary tract infections than men (61.1 vs.
20.0%, p = 0.005). Cystoscopy at first presentation to the urologist was more
often performed in men than women (88.0 vs. 66.7%, p = 0.068), with a more
favorable tumor detection rate at first cystoscopy in men (96.0 vs. 50.0%, p <
0.001). CONCLUSIONS: Delayed referral patterns might lead to deferred diagnosis
of UCB and consequently to adverse outcome. Thus, primary care physicians might
consider referring patients with bladder complaints to specialized care earlier.
PMID- 25139298
TI - Preoperative smoking cessation can reduce postoperative complications in gastric
cancer surgery.
AB - BACKGROUND: Despite the close link between cigarette smoking and the development
of gastric cancer, little is known about the effects of cigarette smoking on
surgical outcomes after gastric cancer surgery. The aim of this study was to
investigate whether preoperative smoking status and the duration of smoking
cessation were associated with short-term surgical consequences in gastric cancer
surgery. METHODS: Among 1,489 consecutive patients, 1,335 patients who underwent
curative radical gastrectomy at the Samsung Medical Center between January and
December 2009 were included in the present study. The smoking status was
determined using questionnaires before surgery. Smokers were divided into four
groups according to the duration of smoking cessation preoperatively (<2, 2-4, 4
8, and >8 weeks). The primary endpoint was postoperative complications (wound,
lung, leakage, and bleeding); secondary endpoints were 3-year recurrence-free
survival (RFS) and overall survival (OS). RESULTS: Five hundred twenty-two
patients (39.1 %) were smokers. Smokers had a significantly higher overall
incidence of postoperative complications than nonsmokers (12.3 vs. 5.2 %, P <
0.001, respectively), especially in impaired wound healing, pulmonary problems,
and leakage. Smokers also had more severe complications than nonsmokers. After
adjusting for other risk factors, the odds ratio (95 % CI) for the development of
postoperative complications in the subgroups who stopped smoking <2 weeks, 2-4, 4
8, and >8 weeks preoperatively were 3.35 (1.92-5.83), 0.99 (0.22-4.38), 2.18
(1.00-4.76), and 1.32 (0.70-2.48), respectively, compared with the nonsmokers.
There were no significant differences in 3-year RFS (P = 0.884) and OS (P =
0.258) between smokers and nonsmokers. CONCLUSIONS: Preoperative smoking
cessation for at least 2 weeks will help to reduce the incidence of postoperative
complications in gastric cancer surgery.
PMID- 25139299
TI - Nursing assistants' communication styles in Korean American older adults with
dementia: a review of the literature.
AB - As ethnic diversity increases in the United States with the anticipated increase
in dementia, it is critical to understand the implications of dementia and
culturally appropriate communication for ethnic minority older adults with
dementia. Utilizing the Ethno-Cultural Gerontological Nursing model and the
Progressively Lowered Stress Threshold model, this article describes the
relationship between nursing assistants' communication style and behavioral
symptoms of dementia, focused on Korean American older adults with dementia
residing in nursing homes. The discussion includes reviewing currently available
studies, nursing implications, and suggestions for future studies.
PMID- 25139301
TI - Monitoring of oil pollution at Gemsa Bay and bioremediation capacity of bacterial
isolates with biosurfactants and nanoparticles.
AB - Fifteen crude oil-degrading bacterial isolates were isolated from an oil-polluted
area in Gemsa Bay, Red Sea, Egypt. Two bacterial species showed the highest
growth rate on crude oil hydrocarbons. From an analysis of 16S rRNA sequences,
these isolates were identified as Pseudomonas xanthomarina KMM 1447 and
Pseudomonas stutzeri ATCC 17588. Gas Chromatographic (GC) analysis of the crude
oil remaining in the culture medium after one week at 30 degrees C showed that
the optimum biodegradation of crude petroleum oil was demonstrated at 50% in
medium containing biosurfactant with two types of nanoparticles separately and
two bacterial species. The complete degradation of some different members of
polyaromatics and the percentage biodegradation of other polyaromatics increased
in microcosm containing two different types of nanoparticles with biosurfactant
after 7 days. In conclusion, these bacterial strains may be useful for the
bioremediation process in the Gemsa Bay, Red Sea decreasing oil pollution in this
marine ecosystem.
PMID- 25139300
TI - Establishment of invasive and non-invasive reporter systems to investigate
American elm-Ophiostoma novo-ulmi interactions.
AB - Dutch elm disease (DED), caused by ascomycete fungi in the Ophiostoma genus, is
the most devastating disease of American elm (Ulmus americana) trees. Cerato
ulmin (CU), a hydrophobin secreted by the fungus, has been implicated in the
development of DED, but its role in fungal pathogenicity and virulence remains
uncertain and controversial. Here, we describe reporter systems based on the CU
promoter and three reporter proteins (GFP, GUS and LUC), developed as research
tools for quantitative and qualitative studies of DED in vitro, in vivo and in
planta. A strain of the aggressive species Ophiostoma novo-ulmi was transformed
with the reporter constructs using Agrobacterium-mediated transformation and the
fungal transformants, namely M75-GFP, M75-GUS and M75-LUC, were examined for
mitotic stability after repeated subcultures. The intensity of GFP fluorescence
was strong in M75-GFP spores and hyphae, allowing microscopic investigations of
spore structure, fungal morphogenesis and fungal development. The interaction of
M75-GFP and U. americana callus cells was explored with scanning laser confocal
microscopy facilitating qualitative studies on fungal strategies for the invasion
and penetration of elm cells. M75-GUS was generated to provide an invasive, yet
quantitative approach to study fungal-plant interactions in vitro and in planta.
The generation of M75-LUC transformants was aimed at providing a non-destructive
quantitative approach to study the role of CU in vivo. The sensitivity, low
background signal and linearity of LUC assays all predict a very reliable
approach to investigate and re-test previously claimed roles of this CU in fungal
pathogenicity. These reporter systems provide new tools to investigate plant
pathogen interactions in this complex pathosystem and may aid in better
understanding the development of DED.
PMID- 25139302
TI - Use of indicator chemicals to characterize the plastic fragments ingested by
Laysan albatross.
AB - Laysan albatross (Phoebastria immutabilis) ingest plastic marine debris of a wide
range of shape, sizes and sources. To better characterize this plastic and
provide insights regarding its provenance and persistence in the environment, we
developed a simple method to classify plastic fragments of unknown origin
according to the resin codes used by the Society of Plastics Industry. Known
plastics were analyzed by gas chromatography-mass spectroscopy (GC-MS) to
identify indicator chemicals characteristic of each plastic resin. Application of
this method to fragments of ingested plastic debris from boluses of Laysan
albatross from Kure Atoll, Hawai'i, yielded proportions of 0.8% High Density
Polyethylene, 6.8% Polystyrene, 8.5% Polyethylene Terephthalate, 20.5% Polyvinyl
Chloride and 68.4% Polypropylene. Some fragments were composed of multiple resin
types. These results suggest that infrequently recycled plastics are the dominant
fragments ingested by albatross, and that these are the most prevalent and
persistent resin types in the marine environment.
PMID- 25139303
TI - Causes and risk factors for revision hip preservation surgery.
AB - BACKGROUND: Identifying causes and risk factors for failure of hip preservation
surgery is critical to properly address residual pathological abnormalities in
the revision setting and improve outcomes in this subset of patients. PURPOSE: To
identify the structural causes of failure in both open and arthroscopic hip
preservation procedures and to identify demographic and radiographic risk factors
that correlate with the need for revision surgery. STUDY DESIGN: Cross-sectional
study; Level of evidence, 3. METHODS: A single-center hip preservation registry
was reviewed (N = 1898 procedures in 1600 patients) to identify 147 patients (n =
152 procedures) who had undergone previous pelvic surgery. Exclusion criteria
included residual deformity from pediatric hip disease (n = 5 patients).
Preoperative demographics, intraoperative findings, radiographic data, and
clinical outcome scores were compared between cohorts with and without revision
surgery in the registry. Postoperative, short-term patient-reported outcome
scores for the revision cohort were described. RESULTS: The most common reason
for revision was residual intra-articular femoroacetabular impingement (74.8%),
followed by extra-articular impingement (9.5%). The majority of revision cases
(78.9%) could be addressed with arthroscopic surgery, with the exception of extra
articular impingement or residual acetabular dysplasia, which necessitated open
approaches. Patients who underwent revision were more likely to be female, were
younger in age, and had worse preoperative outcome scores than did those in the
primary cohort. Abnormal femoral version and the presence of acetabular dysplasia
were not significantly different between the revision and primary cohorts. Short
term improvements in patient-reported outcome scores were found in the revision
cohort at a mean of 15.0 months from the last revision surgery. CONCLUSION:
Residual intra- and extra-articular impingement were the most common reasons for
revision in this cohort. Patients who underwent revision tended to be younger in
age, were female, and had worse preoperative hip functional outcomes than did
those in the primary cohort. Abnormal femoral version or acetabular coverage was
not increased in our revision cohort.
PMID- 25139305
TI - Abstracts of the XXXIXth Sir Peter Freyer Memorial Lecture and Surgical
Symposium, September 5-6, 2014, Galway, Ireland.
PMID- 25139306
TI - Abstracts of the Joint Annual Scientific Meeting of the Irish Association of
Vascular Surgeons and the Northern Ireland Vascular Society, May 2014.
PMID- 25139304
TI - Pharmacologic cholinesterase inhibition improves survival in acetaminophen
induced acute liver failure in the mouse.
AB - BACKGROUND: Acetaminophen (APAP) is one of the most widely used analgesic and
antipyretic pharmaceutical substances in the world and accounts for most cases of
drug induced liver injury resulting in acute liver failure. Acute liver failure
initiates a sterile inflammatory response with release of cytokines and innate
immune cell infiltration in the liver. This study investigates, whether
pharmacologic acetylcholinesterase inhibition with neostigmine diminishes liver
damage in acute liver failure via the cholinergic anti-inflammatory pathway.
METHODS: Acute liver failure was induced in BALB/c mice by a toxic dose of
acetaminophen (APAP). Neostigmine and/or N-acetyl-cysteine (NAC) were applied
therapeutically at set time points and the survival was investigated. Liver
damage was assessed by serum parameters, histopathology and serum cytokine assays
12 h after initiation of acute liver failure. RESULTS: Serum parameters,
histopathology and serum cytokine assays showed pronounced features of acute
liver failure 12 h after application of acetaminophen (APAP). Neostigmine
treatment led to significant reduction of serum liver enzymes (LDH (47,147 +/-
12,726 IU/l vs. 15,822 +/- 10,629 IU/l, p = 0.0014) and ALT (18,048 +/- 4,287
IU/l vs. 7,585 +/- 5,336 IU/l, p = 0.0013), APAP-alone-treated mice vs. APAP +
neostigmine-treated mice), inflammatory cytokine levels (IL-1beta (147 +/- 19 vs.
110 +/- 25, p = 0.0138) and TNF-alpha (184 +/- 23 vs. 130 +/- 33, p = 0.0086),
APAP-alone-treated mice vs. APAP + neostigmine-treated mice) and
histopathological signs of damage.Animals treated with NAC in combination with
the peripheral cholinesterase inhibitor neostigmine showed prolonged survival and
improved outcome. CONCLUSIONS: Neostigmine is an acetylcholinesterase inhibitor
that ameliorates the effects of APAP-induced acute liver failure in the mouse and
therefore may provide new treatment options for affected patients.
PMID- 25139307
TI - Factors associated with long diagnostic delay in celiac disease.
AB - OBJECTIVE: Here, we investigated the factors associated with long diagnostic
delay in celiac disease and the impact of the national Current Care Guidelines in
reducing the delay. MATERIAL AND METHODS: This population-based study involved
825 adult celiac disease patients. The diagnosis was considered delayed when the
interval between first symptoms and diagnosis was >10 years. The patients were
asked about the duration and type of symptoms before diagnosis, time and site
(tertiary, secondary, or primary care) of the diagnosis, family history of the
disease, and presence of significant comorbidities. Analysis was performed by
binary logistic regression. RESULTS: Altogether, 261 (32%) out of 825
participants reported a diagnostic delay of >10 years. Female gender,
neurological or musculoskeletal disorders and presence of diarrhea, abdominal
pain, and malabsorption were associated with prolonged delay. Male gender,
diagnosis after the introduction of the first Current Care Guidelines in 1997,
and being detected by serological screening, and family history of celiac disease
were associated with a lower risk of delayed diagnosis. Factors not associated
with the delay were site of diagnosis, age, and presence of dermatitis
herpetiformis, type 1 diabetes, or thyroidal disease. CONCLUSION: The number of
long diagnostic delays in celiac disease has decreased over the past decades. The
shift of diagnostics from secondary and tertiary care to primary care has not
been detrimental. National guidelines together with increased awareness and
active screening in at-risk groups of celiac disease are important in these
circumstances.
PMID- 25139308
TI - When you smile, you become happy: evidence from resting state task-based fMRI.
AB - Simulation studies on emotion have shown that facial actions can initiate and
modulate particular emotions. However, the neural mechanisms of these initiating
and modulating functions are unclear. In this study, we used resting-state
functional magnetic resonance imaging (fMRI) and task-based fMRI to explore these
processes by examining spontaneous cerebral activities and brain activations
under two conditions: holding a pen using only the teeth (HPT: facilitating the
muscles typically associated with smiling) and holding a pen using only the lips
(HPL: inhibiting the muscles typically associated with smiling). The resting
state fMRI results showed that compared with the HPL condition, significant
increases in the amplitudes of low-frequency fluctuations were found in the right
posterior cingulate gyrus [PCG; Brodmann area 31 (BA31)] and in the left middle
frontal gyrus (MFG; BA9) in the HPT condition. These findings might be related to
the initiation of positive emotions (PCG) and to the control and allocation of
attention (MFG). The task-based fMRI results showed that the inferior parietal
lobule, left supplementary motor area, superior parietal lobule, precuneus, and
bilateral middle cingulum were active when facial manipulation influenced the
recognition of emotional facial expressions. These results demonstrate that
facial actions might not only initiate a particular emotion and draw attention,
but also influence face-based emotion recognition.
PMID- 25139309
TI - Combination of LED light and platelet-derived growth factor to accelerate
dentoalveolar osteogenesis.
AB - AIM: This study aimed to evaluate the adjunctive effect of LED light in platelet
derived growth factor (PDGF)-aided dentoalveolar osteogenesis. MATERIAL AND
METHODS: Full-thickness osseous wounds were created on rat maxillae and were
either unfilled or filled with poly-(D,L-lactide) and poly-(D,L-lactide-co
glycolide) microspheres encapsulating PDGF. Animals received daily 660 +/- 25 nm
LED light irradiation at 0, 10 (LD), or 20 (HD) J/cm(2) , were killed at days 4
28 (n = 6/group/time) and evaluated by microcomputed tomography (micro-CT),
histology, and the expressions of osteopontin and tartrate-resistant acid
phosphatase (TRAP). RESULTS: Greater osteogenesis was noted in the PDGF-treated
defects at day 14. Under the LED light irradiation, osteogenesis was
significantly greater in both LD and HD groups of the non-PDGF-treated defects,
but only in the LD group of the PDGF-treated defects. No significant differences
in osteogenesis among groups were noted at day 28. Greater bone marrow space was
noted in the LED light-irradiated specimens, especially in the PDGF-treated
defects at both time points. Osteopontin was significantly promoted in the LD
group at both time points, and TRAP was significantly promoted in all LED light
irradiated groups at day 28. CONCLUSION: LED light could an adjunct to promote
early PDGF-aided dentoalveolar osteogenesis by facilitating the osteoblast
osteoclast coupling.
PMID- 25139311
TI - Abstracts of the Joint meeting of the Federation of European Physiological
Societies (FEPS) and the Hungarian Physiological Society, 27-30 August 2014,
Budapest, Hungary.
PMID- 25139310
TI - Transcriptional responses of the bacterial antagonist Serratia plymuthica to the
fungal phytopathogen Rhizoctonia solani.
AB - Rhizobacteria with biocontrol ability exploit a range of mechanisms to compete
successfully with other microorganisms and to ensure their growth and survival in
the rhizosphere, ultimately promoting plant growth. The rhizobacterium Serratia
plymuthica AS13 is able to promote oilseed rape growth and improve seedling
survival in the presence of the fungal pathogen, Rhizoctonia solani AG 2-1;
however, our understanding of the mechanisms underlying the antagonism of
Serratia is limited. To elucidate possible mechanisms, genome-wide gene
expression profiling of S. plymuthica AS13 was carried out in the presence or
absence of R. solani. We used RNA sequencing methodology to obtain a
comprehensive overview of Serratia gene expression in response to R. solani. The
differential gene expression profiles of S. plymuthica AS13 revealed
significantly increased expression of genes related to the biosynthesis of the
antibiotic pyrrolnitrin (prnABCD), protease production and transporters. The
results presented here provide evidence that antibiosis is a major functional
mechanism underlying the antagonistic behaviour of S. plymuthica AS13.
PMID- 25139312
TI - Canine progenitor epidermal keratinocytes express various inflammatory markers,
including interleukin-8 and CD40, which are affected by certain antibiotics.
AB - BACKGROUND: Bacterial skin infections are common in dogs and humans.
Keratinocytes have phenotypic features of nonprofessional antigen-presenting
cells and express various cytokines. However, little is known about the effects
of antibiotics on inflammatory markers in canine keratinocytes.
HYPOTHESIS/OBJECTIVES: To investigate inflammatory markers in canine progenitor
epidermal keratinocytes (CPEKs) and to determine the effects of selected
antibiotics on these markers. METHODS: The CPEKs were exposed for 2-24 h to three
concentrations of amoxicillin, cefalexin, sulfadimethoxine, sulfamethoxazole (or
its nitroso metabolite), amikacin or enrofloxacin. Enzyme-linked immunosorbent
assay (ELISA) and immunocytochemistry were used to detect major
histocompatibility complex (MHC) II. CD40 and CXCR1 [interleukin (IL)-8 receptor]
were detected using ELISA. Secreted cytokines/chemokines were quantified using a
multiplex kit. RESULTS: No MHC II protein was detected. CD40 protein was found at
24 h, with levels being significantly increased by enrofloxacin. The CPEKs
secreted no detectable monocyte chemotactic protein-1; undetectable to low
(picogram per millilitre range) concentrations of IL-6, IL-7, IL-10, IL-15,
tumour necrosis factor-alpha, interferon-gamma and granulocyte-macrophage colony
stimulating factor; and high (nanogram per millilitre range) concentrations of IL
8. Levels of IL-8 increased over 24 h following cell proliferation. They were
significantly increased by enrofloxacin after 8 h, and by cefalexin,
sulfadimethoxine, sulfamethoxazole, its nitroso metabolite and enrofloxacin after
24 h. The CPEKs expressed CXCR1. CONCLUSIONS AND CLINICAL IMPORTANCE: Canine
progenitor epidermal keratinocytes express various inflammatory proteins, with
expression profiles being affected by certain antibiotics. This supports previous
work showing keratinocytes to be mediators of inflammation and demonstrates the
potential pro-inflammatory effects of certain antibiotics in the skin.
PMID- 25139313
TI - Update on ultra-long-acting beta agonists in chronic obstructive pulmonary
disease.
AB - INTRODUCTION: For the last two decades, long-acting beta agonists (LABAs) have
been a cornerstone in the management of chronic obstructive pulmonary disease
(COPD). They relax airway smooth muscle and augment expiratory airflow, which
reduces hyperinflation and improves dyspnea, functional capacity and quality of
life. In recent years, Indacaterol, a LABA with an ultra-long duration of action
(ultra-LABA), which only requires once-daily dosing, was approved by the FDA. The
clinical efficacy of indacaterol is comparable, and, in some aspects better, than
the currently available LABAs. AREAS COVERED: This article reviews the
pharmacological properties, clinical efficacy, safety and potential role of the
ultra-LABAs in COPD management. EXPERT OPINION: Ultra-LABAs are effective
bronchodilators with a prolonged duration of action. By decreasing dosing
frequency, ultra-LABAs potentially may improve respiratory medication adherence,
which is associated with better survival and less healthcare utilization. In
addition to their salubrious benefits, beta agonists may produce untoward
effects. Increased mortality and hospitalizations among patients with left
ventricular heart failure, who were treated with beta agonists, has caused
concern about their use in patients with COPD and heart disease. Further
experience and testing will determine the optimal role of ultra-LABAs in the
management of COPD.
PMID- 25139314
TI - Disseminated intravascular coagulation secondary to advanced pancreatic cancer
treated successfully with combination chemotherapy.
AB - Both solid and hematologic malignancies may be complicated by coagulopathies.
Disseminated intravascular coagulation (DIC) in the presence of pancreatic cancer
is generally unrecognized and may have fatal consequences. The diagnosis of DIC
in a patient with advanced cancer is a poor prognostic indicator. Presented here
is a case study consisting of two patients presenting with a new diagnosis of
pancreatic cancer complicated by DIC. Aggressive supportive treatment in addition
to systemic chemotherapy consisting of gemcitabine and nab-paclitaxel was
initiated and DIC was controlled. An early diagnosis of DIC and the
administration of systemic chemotherapy with a high response rate and an ability
to reduce tumor bulk rapidly may offer some patients the probability of recovery.
PMID- 25139315
TI - Emotion regulation and the temporal dynamics of emotions: Effects of cognitive
reappraisal and expressive suppression on emotional inertia.
AB - The tendency for emotions to be predictable over time, labelled emotional
inertia, has been linked to low well-being and is thought to reflect impaired
emotion regulation. However, almost no studies have examined how emotion
regulation relates to emotional inertia. We examined the effects of cognitive
reappraisal and expressive suppression on the inertia of behavioural, subjective
and physiological measures of emotion. In Study 1 (N = 111), trait suppression
was associated with higher inertia of negative behaviours. We replicated this
finding experimentally in Study 2 (N = 186). Furthermore, in Study 2, instructed
suppressors and reappraisers both showed higher inertia of positive behaviours,
and reappraisers displayed higher inertia of heart rate. Neither suppression nor
reappraisal were associated with the inertia of subjective feelings in either
study. Thus, the effects of suppression and reappraisal on the temporal dynamics
of emotions depend on the valence and emotional response component in question.
PMID- 25139316
TI - The intramuscular glucagon stimulation test does not provide good discrimination
between normal and inadequate ACTH reserve when used in the investigation of
short healthy children.
AB - BACKGROUND/AIMS: Few studies have addressed the role of the glucagon stimulation
test (GST) in evaluating the hypothalamic-pituitary-adrenal axis in children. We
investigated the diagnostic value of the GST in evaluating the adrenocortical
response in short healthy children. METHODS: The GST was performed in 190
children investigated for short stature. A peak cortisol >500 nmol/l was
considered a normal response. In the 45 (23.7%) with subnormal response, a 250
MUg ACTH test was done. RESULTS: The rate of subnormal adrenal response to GST
was higher among boys (33.9 vs. 8.9%, p < 0.001) and among children >=6 years
than among younger children (32.7 vs. 18.4%, p < 0.02). Both mean basal and peak
cortisol levels were higher in girls than in boys: 381 +/- 165 vs. 319 +/- 151
nmol/l (p = 0.003) and 741 +/- 102 vs. 595 +/- 208 nmol/l (p < 0.001),
respectively. Peak cortisol on GST was associated with basal cortisol (r = 0.45,
p < 0.001) but not with glucose nadir (r = -0.31, p = 0.67), peak GH (r = 0.069,
p = 0.33) or BMI-SDS (r = -0.08, p = 0.28). Peak cortisol was >500 nmol/l in all
the patients undergoing an ACTH stimulation test. CONCLUSIONS: Since adrenal
response to GST is age- and gender-related and the false-positive rate is high,
its routine performance in healthy children warrants reconsideration.
PMID- 25139317
TI - Transdermal uptake and organ distribution of silver from two different wound
dressings in rats after a burn trauma.
AB - Silver-containing wound dressings are an integral part of wound therapy in adult
and pediatric burn patients. The antimicrobial effect of silver is well known and
has been described in numerous studies. Side effects are rarely reported from
silver-containing wound care products, even though systemic absorption of silver
has been shown by elevated levels of silver in the blood of patients after silver
exposure during wound therapy. This animal study investigated the silver levels
of blood and in which organs and tissues silver is detectable after long-term
application of silver-containing wound dressings after a burn trauma. In male
rats, a major full-thickness scald was created on their backs according to a
standardized burn model. Two different silver-containing wound dressings
(nanocrystalline silver [NCS] and silver sulphate foam [SSF]) were applied
initially and changed every 7 days. Weekly blood drawings revealed an increase of
blood silver in week three with significant higher values in the SSF compared
with NCS group (Ag MUg/kg 135.8 vs. 61.7; means; p <= 0.05). Thereafter, the NCS
group showed significantly higher blood silver levels than the SSF group at week
five (Ag MUg/kg 192.3 vs. 81.3; means; p <= 0.01) and six (Ag MUg/kg 168.2 vs.
32.9; means; p <= 0.01). After 6 weeks, the animals were sacrificed, and the
organs and tissues were analyzed for their silver content by inductively coupled
plasma mass-spectrometry. Silver was detectable in all analyzed organs and tissue
samples, with higher silver values in parenchymatous organs in the NCS than SSF
group (Ag MUg/kg; spleen: 3,469 vs. 260; kidney: 3,186 vs. 289; liver: 2,022 vs.
313; means; p <= 0.05). Silver was also detectable in brain, testis, lung, heart,
and muscle tissue.
PMID- 25139319
TI - A family cluster of negative T-waves reversible after hyperventilation in young
brothers without epicardial coronary disease.
PMID- 25139318
TI - Acquired von Willebrand syndrome in adult patients with congenital heart disease.
AB - OBJECTIVES: Postoperative bleeding is common in patients with congenital heart
disease (CHD). However, little is known about the role and prevalence of acquired
von Willebrand syndrome (AVWS). METHODS: We evaluated the prevalence of AVWS in
relation to underlying cardiac defects, operative procedures and the presence of
Eisenmenger syndrome. The prothrombin time, aPTT, platelet function analysis (PFA
100), von Willebrand factor antigen (VWF:Ag), VWF activity, VWF collagen binding
activity (VWF:CB), factor VIII activity and multimeric analysis were measured in
addition to tests evaluating heart, liver and kidney functions. RESULTS: A total
of 221 patients were screened and 192 patients were included in the study. The
overall prevalence of AVWS was 20.8%. AVWS was identified across all of the
cardiac defects, with the highest prevalence in the defects of great complexity
(38.6% compared to 9.4% in patients with CHD of simple/moderate complexity,
p<0.001), Eisenmenger syndrome (p<0.001) and more severe heart failure symptoms
(NYHA III/IV vs. NYHA I, p<0.001; NYHA III/IV vs. NYHA II, p=0.044). A
combination of multimeric analysis, VWF:CB to VWF:Ag ratio (sensitivity: 77.5%,
specificity: 93.3%) and PFA-100 (PFA Col/Epi sens.: 77%, spec.: 52%; PFA Col/ADP
sens.: 75%, spec.: 74.3%) were used to detect AVWS. CONCLUSIONS: This study
demonstrated that AVWS occurred in patients with various congenital cardiac
defects, but the highest prevalence occurred in the patients with complex CHD and
Eisenmenger syndrome. We, therefore, suggest preoperative screening for AVWS in
all of the patients with CHD, particularly in the patients with CHD of greater
complexity and suffering from Eisenmenger syndrome.
PMID- 25139320
TI - Life threatening iatrogenic abnormal venous return following atrial septal defect
surgery.
PMID- 25139322
TI - A safe and easy technique to sample the coronary sinus--facilitating a closer
look at cardiac disease.
PMID- 25139321
TI - Atorvastatin treatment improves the effects of mesenchymal stem cell
transplantation on acute myocardial infarction: the role of the RhoA/ROCK/ERK
pathway.
AB - BACKGROUND: Statins protect mesenchymal stem cells (MSCs) against the harsh
microenvironment and improve the efficacy of MSC transplantation after acute
myocardial infarction (AMI); however, the mechanism remains uncertain.
Furthermore, the transdifferentiation potential of MSCs in the post-infarct heart
remains highly controversial. The RhoA/Rho-associated coiled-coil-forming kinase
(ROCK) pathway participates in many aspects of the damaged heart after AMI and
related to the "pleiotropic" effects of statins. This study aimed to explore
whether atorvastatin (ATV) facilitates the survival and therapeutic efficacy of
MSCs via the inhibition of RhoA/ROCK pathway and subsequently its downstream
molecular extracellular regulated protein kinase (ERK1/2), and to investigate the
transdifferentiation potential of MSCs in vivo. METHODS AND RESULTS: Female rats
received myocardial injections of male rat MSCs 30 min after AMI. Four weeks
after AMI, ATV combined with MSC treatment resulted in improved cardiac function
and reduced infarct area. ATV facilitated the MSC survival, as revealed by the
increased expression of Y chromosomal genes and the increased number of Y
chromosome-positive cells; however, no transdifferentiation markers were
observed. ATV inhibited the production of inflammatory cytokines both in vitro
and vivo, accompanied by suppression of ROCK and ERK activities. Geranylgeranyl
pyrophosphate (GGPP) abrogated the effects of ATV in the H9c2 cells under
hypoxia/serum deprivation (H/SD), while the ROCK inhibitor fasudil mimicked the
benefits of ATV after AMI. CONCLUSIONS: ATV improves the post-infarct
microenvironment via RhoA/ROCK/ERK inhibition and thus facilitates the survival
and efficacy of implanted MSCs. Transdifferentiation may be not responsible for
the cardiac benefits that follow MSC transplantation.
PMID- 25139323
TI - Residual platelet reactivity and outcomes with 5 mg prasugrel therapy in elderly
patients undergoing percutaneous coronary intervention.
AB - BACKGROUND: In acute coronary syndrome (ACS) patients older than 75 years old,
prasugrel 10 mg maintenance therapy has shown less clinical efficacy and higher
risk of bleeding. In patients older than 75 years, a prasugrel dose of 5 mg
should be used if treatment is deemed necessary. OBJECTIVE: The aim of this study
was to compare platelet reactivity and outcomes in elderly patients receiving
prasugrel 5mg therapy with non-elderly patients receiving prasugrel 10 mg
therapy. METHODS AND RESULTS: Consecutive ACS patients undergoing percutaneous
coronary intervention (PCI) treated with prasugrel were included. Of 718
patients, 228 (32%) had >=75 years and received prasugrel 5 mg/day. Residual
platelet reactivity (RPR) was 47+/-18% and 36+/-16% in the elderly and non
elderly group, respectively (p=0.001). High RPR (>=70%) was found in 9% and 2%
(p=0.0001) in elderly and non-elderly patients, respectively. In the 6-month
follow-up, there was no difference in mortality, stent thrombosis, and
reinfarction rates between the 2 groups but a higher rate of TIMI minor bleeding
(7.9% vs 2.4%; p=0.001) in elderly as compared with younger patients. Age>=75
years was independently associated with bleeding events (HR 2.162 [1.105-4.229];
p=0.024). CONCLUSIONS: Elderly patients receiving prasugrel 5mg are more likely
to experience high RPR than younger patients treated by prasugrel 10 mg. Despite
the use of a reduced prasugrel maintenance dose and a higher level of RPR,
elderly patients show increased risk of bleeding during prasugrel therapy as
compared to younger patients.
PMID- 25139324
TI - Comparative evaluation of HAS-BLED and ATRIA scores by investigating the full
potential of their bleeding prediction schemes in non-valvular atrial
fibrillation patients on vitamin-K antagonists.
PMID- 25139325
TI - Experimental assessment of the effects of sublethal salinities on growth
performance and stress in cultured tra catfish (Pangasianodon hypophthalmus).
AB - The effects of a range of different sublethal salinities were assessed on
physiological processes and growth performance in the freshwater 'tra' catfish
(Pangasianodon hypophthalmus) juveniles over an 8-week experiment. Fish were
distributed randomly among 6 salinity treatments [2, 6, 10, 14 and 18 g/L of
salinity and a control (0 g/L)] with a subsequent 13-day period of acclimation.
Low salinity conditions from 2 to 10 g/L provided optimal conditions with high
survival and good growth performance, while 0 g/L and salinities >14 g/L gave
poorer survival rates (p < 0.05). Salinity levels from freshwater to 10 g/L did
not have any negative effects on fish weight gain, daily weight gain, or specific
growth rate. Food conversion ratio, however, was lowest in the control treatment
(p < 0.05) and highest at the maximum salinities tested (18 g/L treatment).
Cortisol levels were elevated in the 14 and 18 g/L treatments after 6 h and
reached a peak after 24-h exposure, and this also led to increases in plasma
glucose concentration. After 14 days, surviving fish in all treatments appeared
to have acclimated to their respective conditions with cortisol levels remaining
under 5 ng/mL with glucose concentrations stable. Tra catfish do not appear to be
efficient osmoregulators when salinity levels exceed 10 g/L, and at raised
salinity levels, growth performance is compromised. In general, results of this
study confirm that providing culture environments in the Mekong River Basin do
not exceed 10 g/L salinity and that cultured tra catfish can continue to perform
well.
PMID- 25139326
TI - 2-Phenylethynesulfonamide (PES) uncovers a necrotic process regulated by
oxidative stress and p53.
AB - 2-Phenylethynesulfonamide (PES) or pifithrin-MU is a promising anticancer agent
with preferential toxicity for cancer cells. The type of cell death and the
molecular cascades activated by this compound are controversial. Here, we
demonstrate PES elicits a caspase- and BAX/BAK-independent non-necroptotic
necrotic cell death, since it is not inhibited by necrostatin-1. This process is
characterized by an early generation of reactive oxygen species (ROS) resulting
in p53 up-regulation. Accordingly, thiolic antioxidants protect cells from PES
induced death. Furthermore, inhibiting the natural sources of glutathione with l
buthionine-sulfoximine (BSO) strongly cooperates with PES in triggering
cytotoxicity. Genetically modified p53-null or p53 knocked-down cells show
resistance to PES-driven necrosis. The predominant localization of p53 in
chromatin-enriched fractions added to the up-regulation of the p53-responsive
gene p21, strongly suggest the involvement of a transcription-dependent p53
program. On the other hand, we report an augmented production of ROS in p53
positive cells that, added to the increased p53 content in response to PES
elicited ROS, suggests that p53 and ROS are mutually regulated in response to
PES. In sum, p53 up-regulation by ROS triggers a positive feedback loop
responsible of further increasing ROS production and reinforcing PES-driven non
necroptotic necrosis.
PMID- 25139331
TI - Neurocognitive predictors of substance use disorders and nicotine dependence in
ADHD probands, their unaffected siblings, and controls: a 4-year prospective
follow-up.
AB - BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a risk factor for
substance use disorders (SUDs) and nicotine dependence (ND). Neurocognitive
deficits may predict the increased risk of developing SUDs and nicotine
dependence. METHODS: This study comprised three groups derived from the Dutch
part of the International Multicenter ADHD Genetics (IMAGE) study: ADHD probands
(n = 294), unaffected siblings (n = 161), and controls (n = 214). At baseline
(age = 12.2), a range of neurocognitive functions was assessed including
executive functions (inhibition, working memory, timing), measures of motor
functioning (motor timing and tracking) and IQ. After a mean follow-up of 4.2
years, SUDs and ND were assessed. RESULTS: None of the neurocognitive functions
predicted later SUDs or ND in ADHD probands, even after controlling for
medication use and conduct disorder. Slower response inhibition predicted later
nicotine dependence in unaffected siblings (OR = 2.06, 95% CI = 1.22-3.48), and
lower IQ predicted increased risk for SUDs in controls (OR = 1.96, 95% CI = 1.12
3.44). CONCLUSIONS: Cold executive functions, motor functioning, and IQ did not
predict the elevated risk of SUDs and ND in ADHD. Future studies should target
'hot' executive functions such as reward processing as risk factors for SUDs or
ND.
PMID- 25139327
TI - Modulating energy arriving at photochemical reaction centers: orange carotenoid
protein-related photoprotection and state transitions.
AB - Photosynthetic organisms tightly regulate the energy arriving to the reaction
centers in order to avoid photodamage or imbalance between the photosystems. To
this purpose, cyanobacteria have developed mechanisms involving relatively rapid
(seconds to minutes) changes in the photosynthetic apparatus. In this review, two
of these processes will be described: orange carotenoid protein(OCP)-related
photoprotection and state transitions which optimize energy distribution between
the two photosystems. The photoactive OCP is a light intensity sensor and an
energy dissipater. Photoactivation depends on light intensity and only the red
active OCP form, by interacting with phycobilisome cores, increases thermal
energy dissipation at the level of the antenna. A second protein, the
"fluorescence recovery protein", is needed to recover full antenna capacity under
low light conditions. This protein accelerates OCP conversion to the inactive
orange form and plays a role in dislodging the red OCP protein from the
phycobilisome. The mechanism of state transitions is still controversial. Changes
in the redox state of the plastoquinone pool induce movement of phycobilisomes
and/or photosystems leading to redistribution of energy absorbed by
phycobilisomes between PSII and PSI and/or to changes in excitation energy
spillover between photosystems. The different steps going from the induction of
redox changes to movement of phycobilisomes or photosystems remain to be
elucidated.
PMID- 25139332
TI - Lack of association between the 389C>T polymorphism (rs769217) in the catalase
(CAT) gene and the risk of vitiligo: an update by meta-analysis.
AB - BACKGROUND/OBJECTIVES: The catalase (CAT) T/C at codon 389 in the exon 9
polymorphism has been implicated in susceptibility to vitiligo but a large number
of studies have reported inconclusive results. The purpose of this study is to
evaluate the association between the catalase gene polymorphism (389C>T) and the
risk of vitiligo. METHODS: A meta-analysis was carried out to analyse the
association between 389C>T and vitiligo risk. RESULTS: Eight case-control studies
with 2923 cases and 4237 controls were included in the meta-analysis. The results
indicated that there was no association between this polymorphism and vitiligo
(TT + CT versus CC: OR = 1.08, 95% CI = 0.98-1.20, P = 0.11, T versus C: OR =
1.07, 95% CI = 0.99-1.16, P = 0.092). In a subgroup analysis by ethnicity, no
significant association between the CAT gene 389C>T polymorphism and vitiligo
susceptibility was found in Caucasians (TT + CT versus CC: OR = 1.15, 95% CI =
0.98-1.35, P = 0.08; T versus C: OR = 1.07, 95% CI = 0.97-1.19, P = 0.173) and
Asians (TT + CT versus CC: OR = 1.12, 95% CI =0.93-1.34, P = 0.23; T versus C: OR
= 1.07, 95% CI = 0.94-1.21, P = 0.321). CONCLUSIONS: Our results suggest that
389C>T may not contribute to vitiligo susceptibility. However, larger primary
studies with the consideration of gene-environment and gene-gene interactions are
still required to further evaluate the interaction of CAT gene polymorphism with
vitiligo susceptibility.
PMID- 25139333
TI - Diagnostic and prognostic value of preoperative combined GFAP, IGFBP-2, and YKL
40 plasma levels in patients with glioblastoma.
AB - BACKGROUND: Circulating proteins released by tumor cells have recently been
investigated as potential single surrogate biomarkers for glioblastoma multiforme
(GBM). The aim of the current hypothesis-generating study was to evaluate the
diagnostic and prognostic role of preoperative insulin-like growth factor-binding
protein 2 (IGFBP-2), chitinase-3-like protein 1 (YKL-40), and glial fibrillary
acidic protein (GFAP) plasma levels in patients with GBM, both as single markers
and as a combined profile. METHODS: Plasma samples from 111 patients with GBM and
a subset of 40 patients with nonglial brain tumors were obtained preoperatively.
Plasma from 99 healthy controls was also analyzed. IGFBP-2, YKL-40, and GFAP
levels were determined using enzyme-linked immunoadsorbent assay tests. Their
association with histological and radiological variables was assessed. RESULTS:
Circulating levels of all 3 proteins were found to be significantly higher in
patients with GBM compared with healthy controls (P < .01). Only YKL-40 and GFAP
were found to demonstrate significant differences between patients with GBM and
nonglial brain tumors (P = .04). GFAP was undetectable (<0.02 ng/mL) in all
patients without GBM. A receiver operating characteristic analysis accounting for
a 2-step diagnostic procedure including the 3 biomarkers afforded an area under
the curve of 0.77 for differentiating patients with GBM from those with nonglial
brain tumors. There was a significant correlation between tumor volume and plasma
IGFBP-2 level (Spearman Rho correlation coefficient, 0.22; P = .025) and GFAP
(Spearman Rho correlation coefficient, 0.36; P < .001) among patients with GBM.
Preoperative plasma IGFBP-2 levels were found to be independently associated with
worse overall survival among patients with GBM (hazard ratio, 1.3; P = .05).
CONCLUSIONS: A combined profile of preoperative IGFBP-2, GFAP, and YKL-40 plasma
levels could serve as an additional diagnostic tool for patients with inoperable
brain lesions suggestive of GBM. In addition, IGFBP-2 levels appear to constitute
an independent prognostic factor in patients with GBM.
PMID- 25139334
TI - Modeling and forecasting the distribution of Vibrio vulnificus in Chesapeake Bay.
AB - AIM: To construct statistical models to predict the presence, abundance and
potential virulence of Vibrio vulnificus in surface waters of Chesapeake Bay for
implementation in ecological forecasting systems. METHODS AND RESULTS: We
evaluated and applied previously published qPCR assays to water samples (n =
1636) collected from Chesapeake Bay from 2007-2010 in conjunction with State
water quality monitoring programmes. A variety of statistical techniques were
used in concert to identify water quality parameters associated with V.
vulnificus presence, abundance and virulence markers in the interest of
developing strong predictive models for use in regional oceanographic modeling
systems. A suite of models are provided to represent the best model fit and
alternatives using environmental variables that allow them to be put to immediate
use in current ecological forecasting efforts. CONCLUSIONS: Environmental
parameters such as temperature, salinity and turbidity are capable of accurately
predicting abundance and distribution of V. vulnificus in Chesapeake Bay. Forcing
these empirical models with output from ocean modeling systems allows for
spatially explicit forecasts for up to 48 h in the future. SIGNIFICANCE AND
IMPACT OF THE STUDY: This study uses one of the largest data sets compiled to
model Vibrio in an estuary, enhances our understanding of environmental
correlates with abundance, distribution and presence of potentially virulent
strains and offers a method to forecast these pathogens that may be replicated in
other regions.
PMID- 25139335
TI - The difference in immune response and IL-12p35 methylation between newborns and
adults.
AB - BACKGROUND: The immune system of newborn is generally depressed by impaired
production of Th1-cell associated cytokines, which results in increased
susceptibility to intracellular pathogens and poor response to vaccinations. For
avoiding abortion, the maternal and fetal immune systems tend to Th2-cell
polarizing cytokines. Besides, IL-12p35 is a determining factor of the
bioactivity of IL-12, which has an important role in the Th1 response. Recently
methylated DNA is known to associate to inhibit transcription. Therefore, we
explored the methylation status of CpG sites upstream of the coding sequence of
the IL-12p35 gene to determine whether neonatal peripheral blood mononuclear cell
(PBMC) synthesis lower level of IL-12 is related to methylated DNA. RESULTS:
PBMCs from adults expressed higher levels of IL-12p40 (p = 0.303) and IL-12p70 (p
= 0.045) and had a strong ability to produce IL-12p35 mRNA (p = 0.01). However,
there was no difference in the methylation status of CpG sites in the promoter of
IL-12p35 between adults and newborns. CONCLUSIONS: We found that PBMC synthesis
of bioactive IL-12p70 was significantly impaired in the neonatal period,
potentially though a reduction in IL-12p35 production. The reeducation in IL
12p35 production might not be due to methylation of the promoter gene. But, the
impairment of IL-12p35 expression during the neonatal period might be caused by
other epigenetic regulation occurs in the chromatin level.
PMID- 25139337
TI - Single-nucleotide polymorphism associations in common with immune responses to
measles and rubella vaccines.
AB - Single-nucleotide polymorphisms (SNPs) in candidate immune response genes were
evaluated for associations with measles- and rubella-specific neutralizing
antibodies, interferon (IFN)-gamma, and interleukin (IL)-6 secretion in two
separate association analyses in a cohort of healthy immunized subjects. We
identified six SNP associations shared between the measles-specific and rubella
specific immune responses, specifically neutralizing antibody titers (DDX58),
secreted IL-6 (IL10RB, IL12B), and secreted IFN-gamma (IFNAR2, TLR4). An intronic
SNP (rs669260) in the antiviral innate immune receptor gene, DDX58, was
significantly associated with increased neutralizing antibody titers for both
measles and rubella viral antigens post-MMR vaccination (p values 0.02 and
0.0002, respectively). Significant associations were also found between IL10RB
(rs2284552; measles study p value 0.006, rubella study p value 0.00008) and IL12B
(rs2546893; measles study p value 0.005, rubella study p value 0.03) gene
polymorphisms and variations in both measles- and rubella virus-specific IL-6
responses. We also identified associations between individual SNPs in the IFNAR2
and TLR4 genes that were associated with IFN-gamma secretion for both measles and
rubella vaccine-specific immune responses. These results are the first to
indicate that there are SNP associations in common across measles and rubella
vaccine immune responses and that SNPs from multiple genes involved in innate and
adaptive immune response regulation may contribute to the overall human antiviral
response.
PMID- 25139336
TI - KIR diversity in Maori and Polynesians: populations in which HLA-B is not a
significant KIR ligand.
AB - HLA class I molecules and killer cell immunoglobulin-like receptors (KIR) form a
diverse system of ligands and receptors that individualize human immune systems
in ways that improve the survival of individuals and populations. Human
settlement of Oceania by island-hopping East and Southeast Asian migrants started
~3,500 years ago. Subsequently, New Zealand was reached ~750 years ago by
ancestral Maori. To examine how this history impacted KIR and HLA diversity, and
their functional interaction, we defined at high resolution the allelic and
haplotype diversity of the 13 expressed KIR genes in 49 Maori and 34 Polynesians.
Eighty KIR variants, including four 'new' alleles, were defined, as were 35
centromeric and 22 telomeric KIR region haplotypes, which combine to give >50
full-length KIR haplotypes. Two new and divergent variant KIR form part of a
telomeric KIR haplotype, which appears derived from Papua New Guinea and was
probably obtained by the Asian migrants en route to Polynesia. Maori and
Polynesian KIR are very similar, but differ significantly from African, European,
Japanese, and Amerindian KIR. Maori and Polynesians have high KIR haplotype
diversity with corresponding allotype diversity being maintained throughout the
KIR locus. Within the population, each individual has a unique combination of HLA
class I and KIR. Characterizing Maori and Polynesians is a paucity of HLA-B
allotypes recognized by KIR. Compensating for this deficiency are high
frequencies (>50 %) of HLA-A allotypes recognized by KIR. These HLA-A allotypes
are ones that modern humans likely acquired from archaic humans at a much earlier
time.
PMID- 25139338
TI - Smoking and risk of low- and high-grade prostate cancer: results from the REDUCE
study.
AB - PURPOSE: Although the relationship between smoking and prostate cancer risk is
inconsistent, some studies show that smoking is associated with prostate cancer
mortality. Whether this reflects delayed diagnosis or direct smoking-related
effects is unknown. REDUCE, which followed biopsy-negative men with protocol
dictated prostate-specific antigen (PSA)-independent biopsies at 2 and 4 years,
provides an opportunity to evaluate smoking and prostate cancer diagnosis with
minimal confounding from screening biases. EXPERIMENTAL DESIGN: Logistic
regression was conducted to test the association between smoking and cancer on
the first on-study biopsy (no cancer, low-grade Gleason 4-6, high-grade Gleason 7
10) in REDUCE. RESULTS: Of 6,240 men with complete data and >=1 on-study biopsy,
2,937 (45.8%) never smoked, 929 (14.5%) were current smokers, and 2,554 (39.8%)
were former smokers. Among men with negative first on-study biopsies, smokers
were 36% less likely to receive a second on-study biopsy (P < 0.001). At first on
study biopsy, 941 (14.7%) men had cancer. Both current and former smoking were
not significantly associated with either total or low-grade prostate cancer (all
P > 0.36). Current (OR = 1.44, P = 0.028) but not former smokers (OR = 1.21, P =
0.12) were at increased risk of high-grade disease. On secondary analysis, there
was an interaction between smoking and body mass index (BMI; Pinteraction =
0.017): current smokers with BMI <= 25 kg/m(2) had an increased risk of low-grade
(OR = 1.54, P = 0.043) and high-grade disease (OR = 2.45, P = 0.002), with null
associations for BMI >= 25 kg/m(2). CONCLUSION: Among men with elevated PSA and
negative pre-study biopsy in REDUCE, in which biopsies were largely PSA
independent, smoking was unrelated to overall prostate cancer diagnosis but was
associated with increased risk of high-grade prostate cancer.
PMID- 25139340
TI - Paracrine network: another step in the complexity of resistance to EGFR blockade?
AB - Increased secretion of EGFR ligands amphiregulin and TGFalpha by limited KRAS
mutant clones is suggested as a paracrine resistance mechanism to anti-EGFR
antibodies in colorectal cancer models. These findings are biologically sound but
need to be replicated, including in the clinical setting, to foresee whether they
are clinically relevant and therapeutically exploitable.
PMID- 25139339
TI - Mismatch repair status and BRAF mutation status in metastatic colorectal cancer
patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies.
AB - PURPOSE: To determine the prevalence and prognostic value of mismatch repair
(MMR) status and its relation to BRAF mutation (BRAF(MT)) status in metastatic
colorectal cancer (mCRC). EXPERIMENTAL DESIGN: A pooled analysis of four phase
III studies in first-line treatment of mCRC (CAIRO, CAIRO2, COIN, and FOCUS) was
performed. Primary outcome parameter was the hazard ratio (HR) for median
progression-free survival (PFS) and overall survival (OS) in relation to MMR and
BRAF. For the pooled analysis, Cox regression analysis was performed on
individual patient data. RESULTS: The primary tumors of 3,063 patients were
analyzed, of which 153 (5.0%) exhibited deficient MMR (dMMR) and 250 (8.2%) a
BRAF(MT). BRAF(MT) was observed in 53 (34.6%) of patients with dMMR tumors
compared with 197 (6.8%) of patients with proficient MMR (pMMR) tumors (P <
0.001). In the pooled dataset, median PFS and OS were significantly worse for
patients with dMMR compared with pMMR tumors [HR, 1.33; 95% confidence interval
(CI), 1.12-1.57 and HR, 1.35; 95% CI, 1.13-1.61, respectively), and for patients
with BRAF(MT) compared with BRAF wild-type (BRAF(WT)) tumors (HR, 1.34; 95% CI,
1.17-1.54 and HR, 1.91; 95% CI, 1.66-2.19, respectively). PFS and OS were
significantly decreased for patients with BRAF(MT) within the group of patients
with pMMR, but not for BRAF status within dMMR, or MMR status within BRAF(WT) or
BRAF(MT). CONCLUSIONS: Prevalence of dMMR and BRAF(MT) in patients with mCRC is
low and both biomarkers confer an inferior prognosis. Our data suggest that the
poor prognosis of dMMR is driven by the BRAF(MT) status.
PMID- 25139343
TI - Ocular and histologic findings in a series of children with infantile pompe
disease treated with enzyme replacement therapy.
AB - PURPOSE: To report the ophthalmologic and histologic findings in a series of
children with infantile Pompe disease treated with enzyme replacement therapy
(ERT). METHODS: Records of children with infantile Pompe disease treated with ERT
who had at least one complete ophthalmic examination and the ocular
histopathology of children with infantile Pompe disease who were treated with ERT
were reviewed. The patients' clinical history, including external ocular
examination, ocular alignment and motility, dilated fundus examination, and
cycloplegic refraction, was evaluated. A literature review was performed for
ophthalmologic findings in infantile Pompe disease using PubMed. RESULTS: The
clinical findings of 13 children were included and the ocular histopathology of 3
children with infantile Pompe disease who were treated with ERT were reviewed.
Forty-six percent (6 of 13) had bilateral ptosis, 23% (3 of 13) had strabismus,
62% (8 of 13) had myopia, and 69% (9 of 13) had astigmatism. On histologic
examination, there was vacuolar myopathy affecting the extraocular muscles,
ciliary body, and iris smooth muscle and glycogen accumulation in corneal
endothelial, lens epithelium, and retinal ganglion cells, and within lysosomes of
scleral fibroblasts. CONCLUSIONS: It is important that ophthalmic providers are
aware of the high prevalence of myopia, astigmatism, and ptosis in children with
infantile Pompe disease treated with ERT because they are potentially amblyogenic
but treatable factors.
PMID- 25139344
TI - Endocrine effects of valproic acid therapy in girls with epilepsy: a prospective
study.
AB - BACKGROUND/AIM: It is controversial whether the endocrine dysfunction in epilepsy
patients is caused by the epilepsy itself, the antiepileptic therapy, or both. We
prospectively evaluated the long-term impact of valproic acid monotherapy
compared to other anti-epileptic drugs on anthropometric, metabolic, hormonal,
and ultrasonographic parameters in girls with epilepsy. METHODS: Fifty-seven
female patients with epilepsy who had started therapy at mean age of 11.5 +/- 3.3
years, 42 with valproic acid (mean dose 13.1 +/- 7.0 mg/kg/day and 15 with other
anti-epileptic agents were followed for a mean of 3.2 years (range 1.0-8.5 years)
in our center. Clinical, hormonal and transabdominal pelvic ultrasound data were
collected at 3 time points: before and 6-12 months after onset of anti-epileptic
drug treatment; and at the last visit while patients were still taking anti
epileptic drugs. RESULTS: There were no significant between-group differences
regarding changes in height, body mass index standard deviation score, levels of
glucose and insulin, or lipid and endocrine profile from first to last visits.
Mean thyroid-stimulating hormone level increased significantly between first and
last visit only in the valproic acid group (p < 0.001), with no significant
difference in free T4 level over time or between groups. The rate of clinical
polycystic ovary syndrome for the valproic acid group (11%) was comparable to
that reported in healthy controls (5-10%). CONCLUSIONS: Administration of
valproic acid had no adverse effect on body weight, metabolic status or endocrine
function over an average follow-up of 3.2 years. Valproic acid appears to be safe
for use in girls with epilepsy.
PMID- 25139345
TI - Successful treatment of cataplexy in patients with early-infantile Niemann-Pick
disease type C: use of tricyclic antidepressants.
AB - Cataplexy is a brief episode of bilateral loss of muscle tone with intact
consciousness, triggered by a variety of strong emotions such as anger, laugh,
humor or surprise and it is considered to represent the physiologic atonia of
rapid eye movement sleep. On the other hand, Niemann-Pick type C is a
neurodegenerative lysosomal storage disease, characterized by the accumulation of
cholesterol and glycosphingolipids. Cataplexy is a relatively specific and common
neurologic sign seen in almost 50% of all patients with Niemann-Pick type C. The
aim of this report is to demonstrate the successful treatment of cataplexy with
the use of a tricyclic antidepressant imipiramine, in two patients between the
ages 6-9, with mild to moderate mental retardation, molecularly diagnosed as
Niemann-Pick type C 1 and currently under miglustat treatment and to discuss the
possible mechanisms of drug action in the light of cataplexy and Niemann-Pick
type C pathophysiology.
PMID- 25139346
TI - The healthcare utilization and cost of treating patients experiencing
inappropriate implantable cardioverter defibrillator shocks: a propensity score
study.
AB - BACKGROUND: Inappropriate shocks (IASs) from implantable cardioverter
defibrillators (ICDs) are associated with decreased quality of life, but whether
they increase healthcare utilization and treatment costs is unknown. We sought to
determine the impact of IASs on subsequent healthcare utilization and treatment
costs. METHODS: We conducted a case-control analysis of ICD patients at a single
institution from 1997 to 2010 and who had >=12 months of post-ICD implant follow
up. Cases included all patients experiencing an IAS during the first 12 months
after implantation. Eligible control patients did not receive a shock of any kind
during the 12 months after implantation. Propensity scores based on 36 covariates
(area under curve = 0.78) were used to match cases to controls. We compared the
rate (occurrences/person year [PY]) of healthcare utilization immediately
following IAS to the end of the 12-month follow-up period to the rate in the no
shock group over 12 months of follow-up. We also compared 12-month postimplant
treatment (outpatient clinic, emergency room, and hospitalization) costs in both
groups. RESULTS: A total of 76 patients experiencing >=1 IAS during the first 12
months after implant (contributing 48 PYs) were matched to 76 no-shock patients
(contributing 76 PYs). Cardiovascular (CV)-related clinic visit and
hospitalization rates were increased following an IAS compared to those not
receiving a shock (4.0 vs 3.3 and 0.7 vs 0.5, respectively, P = 0.02 for both).
CV-related emergency room visitation (0.15 vs 0.08) rates were also numerically
higher following an IAS, but did not reach statistical significance (P = 0.26).
Patients experiencing an IAS accrued greater treatment costs during the 12 months
postimplant compared to no-shock patients ($13,973 +/- $46,345 vs $6,790 +/-
$19,091, P = 0.001). CONCLUSION: Recipients of IAS utilize the healthcare system
more frequently following an IAS than patients not experiencing a shock. This
increased utilization results in higher costs of treating IAS patients during the
12 months postimplant.
PMID- 25139347
TI - Balloon inflation time in angioplasty of dialysis access stenosis.
PMID- 25139349
TI - Reed-Sternberg cell-derived lymphotoxin-alpha activates endothelial cells to
enhance T-cell recruitment in classical Hodgkin lymphoma.
AB - It is known that cells within the inflammatory background in classical Hodgkin
lymphoma (cHL) provide signals essential for the continual survival of the
neoplastic Hodgkin and Reed-Sternberg (HRS) cells. However, the mechanisms
underlying the recruitment of this inflammatory infiltrate into the involved
lymph nodes are less well understood. In this study, we show in vitro that HRS
cells secrete lymphotoxin-alpha (LTalpha) which acts on endothelial cells to
upregulate the expression of adhesion molecules that are important for T cell
recruitment. LTalpha also enhances the expression of hyaluronan which
preferentially contributes to the recruitment of CD4(+) CD45RA(+) naive T cells
under in vitro defined flow conditions. Enhanced expression of LTalpha in HRS
cells and tissue stroma; and hyaluronan on endothelial cells are readily detected
in involved lymph nodes from cHL patients. Our study also shows that although NF
kappaB and AP-1 are involved, the cyclooxygenase (COX) pathway is the dominant
regulator of LTalpha production in HRS cells. Using pharmacological inhibitors,
our data suggest that activity of COX1, but not of COX2, directly regulates the
expression of nuclear c-Fos in HRS cells. Our findings suggest that HRS cell
derived LTalpha is an important mediator that contributes to T cell recruitment
into lesional lymph nodes in cHL.
PMID- 25139348
TI - Export of virulence proteins by malaria-infected erythrocytes involves remodeling
of host actin cytoskeleton.
AB - Following invasion of human red blood cells (RBCs) by the malaria parasite,
Plasmodium falciparum, a remarkable process of remodeling occurs in the host cell
mediated by trafficking of several hundred effector proteins to the RBC
compartment. The exported virulence protein, P falciparum erythrocyte membrane
protein 1 (PfEMP1), is responsible for cytoadherence of infected cells to host
endothelial receptors. Maurer clefts are organelles essential for protein
trafficking, sorting, and assembly of protein complexes. Here we demonstrate that
disruption of PfEMP1 trafficking protein 1 (PfPTP1) function leads to severe
alterations in the architecture of Maurer's clefts. Furthermore, 2 major surface
antigen families, PfEMP1 and STEVOR, are no longer displayed on the host cell
surface leading to ablation of cytoadherence to host receptors. PfPTP1 functions
in a large complex of proteins and is required for linking of Maurer's clefts to
the host actin cytoskeleton.
PMID- 25139350
TI - X chromosome inactivation analysis reveals a difference in the biology of ET
patients with JAK2 and CALR mutations.
AB - Calreticulin mutations (CALR(MUT)) are found in a significant proportion of
patients with essential thrombocythemia (ET) lacking JAK2(V617F) or MPL
mutations. They are associated with substantially different hematological and
clinical features and define a distinct subtype of ET. We show here that their
presence is significantly correlated with a clonal X chromosome inactivation
pattern (XCIP). Of 105 female ET patients investigated, 61 had an interpretable
XCIP, and a clonal pattern was observed in 88% of CALR(MUT) patients compared
with 26% of JAK2(V617F) (P = .0002) and 9% of JAK2(V617F)/MPL/CALR wild-type
patients (P < .0001). Neutrophil CALR(MUT) level was significantly higher than
JAK2(V617F) level (median, 50% vs 18%; P < .0001), and wild-type myelopoiesis was
suppressed in CALR(MUT) but not JAK2(V617F) patients. These data are suggestive
of truly monoclonal hematopoiesis in CALR(MUT) patients and provide further
evidence that the biology associated with CALR mutations is markedly different
from that of JAK2(V617F) mutations.
PMID- 25139352
TI - Molecular and clinical predictors of inhibitor risk and its prevention and
treatment in mild hemophilia A.
AB - The risk for inhibitor development in mild hemophilia A (factor VIII levels
between 5 and 40 U/dL) is larger than previously anticipated, continues
throughout life, and is particularly associated with certain mutations in F8.
Desmopressin may reduce inhibitor risk by avoiding exposure to FVIII
concentrates, but the heterogenous biological response to desmopressin, showing
large interindividual variation, may limit its clinical use. However, predictors
of desmopressin response have been recently identified, allowing the selection of
the best candidates to this treatment.
PMID- 25139353
TI - Phosphoinositide 3-kinase beta mediates microvascular endothelial repair of
thrombotic microangiopathy.
AB - Thrombotic microangiopathy (TMA) commonly involves injury of kidney glomerular
endothelial cells (ECs) and fibrin occlusion of the capillaries. The mechanisms
underlying repair of the microvasculature and recovery of kidney function are
poorly defined. In the developing vasculature, the phosphoinositide 3-kinase
(PI3K) alpha isoform integrates many growth factor cues. However, the role of
individual isoforms in repair of the established vasculature is unclear. We found
that postnatal endothelial deletion of PI3Kbeta sensitizes mice to lethal acute
kidney failure after TMA injury. In vitro, PI3Kbeta-deficient ECs show reduced
angiogenic invasion of fibrin matrix with unaltered sensitivity to proapoptotic
stress compared with wild-type ECs. This correlates with decreased expression of
the EC tip cell markers apelin and Dll4 and is associated with a reduction in
migration and proliferation. In vivo, PI3Kbeta-knockdown ECs are deficient in
assembly of microvessel-like structures. These data identify a critical role for
endothelial PI3Kbeta in microvascular repair following injury.
PMID- 25139351
TI - Inhibition of leukemia cell engraftment and disease progression in mice by
osteoblasts.
AB - The bone marrow niche is thought to act as a permissive microenvironment required
for emergence or progression of hematologic cancers. We hypothesized that
osteoblasts, components of the niche involved in hematopoietic stem cell (HSC)
function, influence the fate of leukemic blasts. We show that osteoblast numbers
decrease by 55% in myelodysplasia and acute myeloid leukemia patients. Further,
genetic depletion of osteoblasts in mouse models of acute leukemia increased
circulating blasts and tumor engraftment in the marrow and spleen leading to
higher tumor burden and shorter survival. Myelopoiesis increased and was coupled
with a reduction in B lymphopoiesis and compromised erythropoiesis, suggesting
that hematopoietic lineage/progression was altered. Treatment of mice with acute
myeloid or lymphoblastic leukemia with a pharmacologic inhibitor of the synthesis
of duodenal serotonin, a hormone suppressing osteoblast numbers, inhibited loss
of osteoblasts. Maintenance of the osteoblast pool restored normal marrow
function, reduced tumor burden, and prolonged survival. Leukemia prevention was
attributable to maintenance of osteoblast numbers because inhibition of serotonin
receptors alone in leukemic blasts did not affect leukemia progression. These
results suggest that osteoblasts play a fundamental role in propagating leukemia
in the marrow and may be a therapeutic target to induce hostility of the niche to
leukemia blasts.
PMID- 25139355
TI - Clonal analysis identifies hemogenic endothelium as the source of the blood
endothelial common lineage in the mouse embryo.
AB - The first blood and endothelial cells of amniote embryos appear in close
association in the blood islands of the yolk sac (YS). This association and in
vitro lineage analyses have suggested a common origin from mesodermal precursors
called hemangioblasts, specified in the primitive streak during gastrulation.
Fate mapping and chimera studies, however, failed to provide strong evidence for
a common origin in the early mouse YS. Additional in vitro studies suggest
instead that mesodermal precursors first generate hemogenic endothelium, which
then generate blood cells in a linear sequence. We conducted an in vivo clonal
analysis to determine the potential of individual cells in the mouse epiblast,
primitive streak, and early YS. We found that early YS blood and endothelial
lineages mostly derive from independent epiblast populations, specified before
gastrulation. Additionally, a subpopulation of the YS endothelium has hemogenic
activity and displays characteristics similar to those found later in the
embryonic hemogenic endothelium. Our results show that the earliest blood and
endothelial cell populations in the mouse embryo are specified independently, and
that hemogenic endothelium first appears in the YS and produces blood precursors
with markers related to definitive hematopoiesis.
PMID- 25139354
TI - The DPY30 subunit in SET1/MLL complexes regulates the proliferation and
differentiation of hematopoietic progenitor cells.
AB - Epigenetic mechanisms, including histone modifications, have emerged as important
factors influencing cell fate determination. The functional role of H3K4
methylation, however, remains largely unclear in the maintenance and
differentiation of hematopoietic stem cells (HSCs)/hematopoietic progenitor cells
(HPCs). Here we show that DPY30, a shared core subunit of the SET1/MLL family
methyltransferase complexes and a facilitator of their H3K4 methylation activity,
is important for ex vivo proliferation and differentiation of human CD34(+) HPCs.
DPY30 promotes HPC proliferation by directly regulating the expression of genes
critical for cell proliferation. Interestingly, while DPY30 knockdown in HPCs
impaired their differentiation into the myelomonocytic lineage, it potently
promoted hemoglobin production and affected the kinetics of their differentiation
into the erythroid lineage. In an in vivo model, we show that morpholino-mediated
dpy30 knockdown resulted in severe defects in the development of the zebrafish
hematopoietic system, which could be partially rescued by coinjection of dpy30
messenger RNA. Taken together, our results establish a critical role of DPY30 in
the proliferation and appropriate differentiation of hematopoietic progenitor
cells and in animal hematopoiesis. Finally, we also demonstrate a crucial role of
DPY30 in the growth of several MLL1-fusion-mediated leukemia cell lines.
PMID- 25139356
TI - Somatic mutations identify a subgroup of aplastic anemia patients who progress to
myelodysplastic syndrome.
AB - The distinction between acquired aplastic anemia (AA) and hypocellular
myelodysplastic syndrome (hMDS) is often difficult, especially nonsevere AA. We
postulated that somatic mutations are present in a subset of AA, and predict
malignant transformation. From our database, we identified 150 AA patients with
no morphological evidence of MDS, who had stored bone marrow (BM) and
constitutional DNA. We excluded Fanconi anemia, mutations of telomere
maintenance, and a family history of BM failure (BMF) or cancer. The initial
cohort of 57 patients was screened for 835 known genes associated with BMF and
myeloid cancer; a second cohort of 93 patients was screened for mutations in
ASXL1, DNMT3A, BCOR, TET2, and MPL. Somatic mutations were detected in 19% of AA,
and included ASXL1 (n = 12), DNMT3A (n = 8) and BCOR (n = 6). Patients with
somatic mutations had a longer disease duration (37 vs 8 months, P < .04), and
shorter telomere lengths (median length, 0.9 vs 1.1, P < .001), compared with
patients without mutations. Somatic mutations in AA patients with a disease
duration of >6 months were associated with a 40% risk of transformation to MDS (P
< .0002). Nearly one-fifth of AA patients harbor mutations in genes typically
seen in myeloid malignancies that predicted for later transformation to MDS.
PMID- 25139357
TI - A nonsense mutation in IKBKB causes combined immunodeficiency.
AB - Identification of the molecular etiologies of primary immunodeficiencies has led
to important insights into the development and function of the immune system. We
report here the cause of combined immunodeficiency in 4 patients from 2 different
consanguineous Qatari families with similar clinical and immunologic phenotypes.
The patients presented at an early age with fungal, viral, and bacterial
infections and hypogammaglobulinemia. Although their B- and T-cell numbers were
normal, they had low regulatory T-cell and NK-cell numbers. Moreover, patients' T
cells were mostly CD45RA(+)-naive cells and were defective in activation after T
cell receptor stimulation. All patients contained the same homozygous nonsense
mutation in IKBKB (R286X), revealed by whole-exome sequencing with undetectable
IKKbeta and severely decreased NEMO proteins. Mutant IKKbeta(R286X) was unable to
complex with IKKalpha/NEMO. Immortalized patient B cells displayed impaired
IkappaBalpha phosphorylation and NFkappaB nuclear translocation. These data
indicate that mutated IKBKB is the likely cause of immunodeficiency in these 4
patients.
PMID- 25139358
TI - Donor CD4+ Foxp3+ regulatory T cells are necessary for posttransplantation
cyclophosphamide-mediated protection against GVHD in mice.
AB - Posttransplantation cyclophosphamide (PTCy) is an effective prophylaxis against
graft-versus-host disease (GVHD). However, it is unknown whether PTCy works
singularly by eliminating alloreactive T cells via DNA alkylation or also by
restoring the conventional (Tcon)/regulatory (Treg) T-cell balance. We studied
the role of Tregs in PTCy-mediated GVHD prophylaxis in murine models of
allogeneic blood or marrow transplantation (alloBMT). In 2 distinct MHC-matched
alloBMT models, infusing Treg-depleted allografts abrogated the GVHD-prophylactic
activity of PTCy. Using allografts in which Foxp3(+) Tregs could be selectively
depleted in vivo, either pre- or post-PTCy ablation of donor thymus-derived Tregs
(tTregs) abolished PTCy protection against GVHD. PTCy treatment was associated
with relative preservation of donor Tregs. Experiments using combinations of
Foxp3(-) Tcons and Foxp3(+) Tregs sorted from different Foxp3 reporter mice
indicated that donor Treg persistence after PTCy treatment was predominantly
caused by survival of functional tTregs that retained Treg-specific demethylation
and also induction of peripherally derived Tregs. Finally, adoptive transfer of
tTregs retrieved from PTCy-treated chimeras rescued PTCy-treated, Treg-depleted
recipients from lethal GVHD. Our findings indicate that PTCy-mediated protection
against GVHD is not singularly dependent on depletion of donor alloreactive T
cells but also requires rapidly recovering donor Tregs to initiate and maintain
alloimmune regulation.
PMID- 25139359
TI - Acute myocardial infarct size is related to periodontitis extent and severity.
AB - Cardiovascular disease has been associated with 40% of deaths in high-income
countries and 28% in lower-income countries. The relationship between
periodontitis and acute myocardial infarction is well documented, but it has not
been established whether the extent and severity of periodontitis influence the
infarct size. This cross-sectional and analytic study was designed to investigate
the association of chronic periodontitis extent and severity with acute
myocardial infarct size as indicated by serum cardiac troponin I and myoglobin
levels. Sociodemographic, periodontal, cardiologic, and hematologic variables
were gathered in 112 consecutive patients with myocardial infarction. The extent
(Arbes Index) and severity (Periodontal Inflammatory Severity Index) of the
chronic periodontitis were significantly associated with troponin I levels after
controlling for sociodemographic and clinical confounders (change in R (2) =
.041, p < .02, and R (2) = .031, p = .04). However, only the extent index
accounted for levels of myoglobin (change in R (2) = .030, p < .05), total
leukocytes (change in R (2) = .041 p < .02), and neutrophils (change in R (2) =
.059, p < .01). Mediated regression analysis showed that leukocytes and
neutrophils may underlie these observed relationships of chronic periodontitis
with troponin I and myoglobin. To our knowledge, this study contributes the first
research data demonstrating that the extent and severity of periodontitis is
positively associated with acute myocardial infarct size as measured by serum
troponin I and myoglobin levels.
PMID- 25139360
TI - In vivo bioreactors for mandibular reconstruction.
AB - Large mandibular defects are difficult to reconstruct with good functional and
aesthetic outcomes because of the complex geometry of craniofacial bone. While
the current gold standard is free tissue flap transfer, this treatment is limited
in fidelity by the shape of the harvested tissue and can result in significant
donor site morbidity. To address these problems, in vivo bioreactors have been
explored as an approach to generate autologous prefabricated tissue flaps. These
bioreactors are implanted in an ectopic site in the body, where ossified tissue
grows into the bioreactor in predefined geometries and local vessels are
recruited to vascularize the developing construct. The prefabricated flap can
then be harvested with vessels and transferred to a mandibular defect for optimal
reconstruction. The objective of this review article is to introduce the concept
of the in vivo bioreactor, describe important preclinical models in the field,
summarize the human cases that have been reported through this strategy, and
offer future directions for this exciting approach.
PMID- 25139361
TI - Fluorapatite-modified scaffold on dental pulp stem cell mineralization.
AB - In previous studies, fluorapatite (FA) crystal-coated surfaces have been shown to
stimulate the differentiation and mineralization of human dental pulp stem cells
(DPSCs) in two-dimensional cell culture. However, whether the FA surface can
recapitulate these properties in three-dimensional culture is still unknown. This
study examined the differences in behavior of human DPSCs cultured on electrospun
polycaprolactone (PCL) NanoECM nanofibers with or without the FA crystals. Under
near-physiologic conditions, the FA crystals were synthesized on the PCL
nanofiber scaffolds. The FA crystals were evenly distributed on the scaffolds.
DPSCs were cultured on the PCL+FA or the PCL scaffolds for up to 28 days.
Scanning electron microscope images showed that DPSCs attached well to both
scaffolds after the initial seeding. However, it appeared that more multicellular
aggregates formed on the PCL+FA scaffolds. After 14 days, the cell proliferation
on the PCL+FA was slower than that on the PCL-only scaffolds. Interestingly, even
without any induction of mineralization, from day 7, the upregulation of several
pro-osteogenic molecules (dmp1, dspp, runx2, ocn, spp1, col1a1) was detected in
cells seeded on the PCL+FA scaffolds. A significant increase in alkaline
phosphatase activity was also seen on FA-coated scaffolds compared with the PCL
only scaffolds at days 14 and 21. At the protein level, osteocalcin expression
was induced only in the DPSCs on the PCL+FA surfaces at day 21 and then
significantly enhanced at day 28. A similar pattern was observed in those
specimens stained with Alizarin red and Von Kossa after 21 and 28 days. These
data suggest that the incorporation of FA crystals within the three-dimensional
PCL nanofiber scaffolds provided a favorable extracellular matrix
microenvironment for the growth, differentiation, and mineralization of human
DPSCs. This FA-modified PCL nanofiber scaffold shows promising potential for
future bone, dental, and orthopedic regenerative applications.
PMID- 25139362
TI - Multiphasic scaffolds for periodontal tissue engineering.
AB - For a successful clinical outcome, periodontal regeneration requires the
coordinated response of multiple soft and hard tissues (periodontal ligament,
gingiva, cementum, and bone) during the wound-healing process. Tissue-engineered
constructs for regeneration of the periodontium must be of a complex 3
dimensional shape and adequate size and demonstrate biomechanical stability over
time. A critical requirement is the ability to promote the formation of
functional periodontal attachment between regenerated alveolar bone, and newly
formed cementum on the root surface. This review outlines the current advances in
multiphasic scaffold fabrication and how these scaffolds can be combined with
cell- and growth factor-based approaches to form tissue-engineered constructs
capable of recapitulating the complex temporal and spatial wound-healing events
that will lead to predictable periodontal regeneration. This can be achieved
through a variety of approaches, with promising strategies characterized by the
use of scaffolds that can deliver and stabilize cells capable of cementogenesis
onto the root surface, provide biomechanical cues that encourage perpendicular
alignment of periodontal fibers to the root surface, and provide osteogenic cues
and appropriate space to facilitate bone regeneration. Progress on the
development of multiphasic constructs for periodontal tissue engineering is in
the early stages of development, and these constructs need to be tested in large
animal models and, ultimately, human clinical trials.
PMID- 25139363
TI - Antibacterial efficacy of exogenous nitric oxide on periodontal pathogens.
AB - Current treatments for periodontitis (e.g., scaling/root planing and
chlorhexidine) have limited efficacy since they fail to suppress microbial
biofilms satisfactorily over time, and the use of adjunctive antimicrobials can
promote the emergence of antibiotic-resistant organisms. Herein, we report the
novel application of nitric oxide (NO)-releasing scaffolds (i.e., dendrimers and
silica particles) as anti-periodontopathogenic agents. The effectiveness of
macromolecular NO release was demonstrated by a 3-log reduction in
periodontopathogenic Aggregatibacter actinomycetemcomitans and Porphyromonas
gingivalis viability. In contrast, Streptococcus mutans and Streptococcus
sanguinis, caries-associated organisms, were substantially less sensitive to NO
treatment. Both dendrimer- and silica-based NO release exhibited substantially
less toxicity to human gingival fibroblasts at concentrations necessary to
eradicate periodontopathogens than did clinical concentrations of chlorhexidine.
These results suggest the potential utility of macromolecular NO-release
scaffolds as a novel platform for the development of periodontal disease
therapeutics.
PMID- 25139364
TI - Advanced biomatrix designs for regenerative therapy of periodontal tissues.
AB - Periodontitis is an inflammatory disease that causes loss of the tooth-supporting
apparatus, including periodontal ligament, cementum, and alveolar bone. A broad
range of treatment options is currently available to restore the structure and
function of the periodontal tissues. A regenerative approach, among others, is
now considered the most promising paradigm for this purpose, harnessing the
unique properties of stem cells. How to make full use of the body's innate
regenerative capacity is thus a key issue. While stem cells and bioactive factors
are essential components in the regenerative processes, matrices play pivotal
roles in recapitulating stem cell functions and potentiating therapeutic actions
of bioactive molecules. Moreover, the positions of appropriate bioactive matrices
relative to the injury site may stimulate the innate regenerative stem cell
populations, removing the need to deliver cells that have been manipulated
outside of the body. In this topical review, we update views on advanced designs
of biomatrices-including mimicking of the native extracellular matrix, providing
mechanical stimulation, activating cell-driven matrices, and delivering bioactive
factors in a controllable manner-which are ultimately useful for the regenerative
therapy of periodontal tissues.
PMID- 25139366
TI - The dynamic impact of repeated stress on the hippocampal spatial map.
AB - Stress alters the function of many physiological processes throughout the body,
including in the brain. A neural circuit particularly vulnerable to the effects
of stress is the hippocampus, a key component of the episodic and spatial memory
system in both humans and rodents. Earlier studies have provided snapshots of
morphological, molecular, physiological and behavioral changes in the hippocampus
following either acute or repeated stress. However, the cumulative impact of
repeated stress on in vivo hippocampal physiology remains unexplored. Here we
report the stress-induced modulation of the spatially receptive fields of the
hippocampal CA1 'place cells' as mice explore familiar and novel tracks after 5
and 10 days of immobilization stress. We find that similar to what has been
observed following acute stress, five days of repeated stress results in
decreased excitability of CA1 pyramidal cells. Following ten days of chronic
stress, however, this decreased hippocampal excitability is no longer evident,
suggesting adaptation may have occurred. In addition to these changes in neuronal
excitability, we find deficient context discrimination, wherein both short-term
and chronic stress impair the ability of the hippocampus to unambiguously
distinguish novel and familiar environments. These results suggest that a loss of
network flexibility may underlie some of the behavioral deficits accompanying
chronic stress.
PMID- 25139367
TI - Long-term prevention of postoperative Crohn's disease recurrence with
azathioprine: the wolf in the sheep clothing.
PMID- 25139368
TI - Amyloidosis presenting as a colonic mass. A case report.
PMID- 25139365
TI - Biomaterials for craniofacial bone engineering.
AB - Conditions such as congenital anomalies, cancers, and trauma can all result in
devastating deficits of bone in the craniofacial skeleton. This can lead to
significant alteration in function and appearance that may have significant
implications for patients. In addition, large bone defects in this area can pose
serious clinical dilemmas, which prove difficult to remedy, even with current
gold standard surgical treatments. The craniofacial skeleton is complex and
serves important functional demands. The necessity to develop new approaches for
craniofacial reconstruction arises from the fact that traditional therapeutic
modalities, such as autologous bone grafting, present myriad limitations and
carry with them the potential for significant complications. While the optimal
bone construct for tissue regeneration remains to be elucidated, much progress
has been made in the past decade. Advances in tissue engineering have led to
innovative scaffold design, complemented by progress in the understanding of stem
cell-based therapy and growth factor enhancement of the healing cascade. This
review focuses on the role of biomaterials for craniofacial bone engineering,
highlighting key advances in scaffold design and development.
PMID- 25139369
TI - Fatal case of hepatic portal venous gas following palliative stenting and
chemotherapy for occlusive advanced colorectal cancer.
PMID- 25139370
TI - Mesenteric fibromatosis.
AB - Mesenteric fibromatosis is a rare, locally invasive, non-metastasizing type of
intra-abdominal fibromatoses with a very high rate of recurrence. Because of
rarity, these tumors pose a diagnostic and therapeutic challenge. These tumors
may remain asymptomatic, but commonly present as a painless mass. There are no
clear treatment guidelines. Surgical excision with wide margin is the preferred
modality of treatment. Medical therapy is indicated for inoperable and recurrent
tumors. There are several isolated case reports on mesenteric fibromatosis with
different and unusual presentations and its complications. Though several studies
have been published on extra-abdominal fibromatosis as well as on extramesenteric
abdominal fibromatosis, but extensive research studies are still lacking on
mesenteric fibromatosis. The aim of this article is to present current knowledge
on mesenteric fibromatosis, our experience of four cases, and comprehensive
review of available literature.
PMID- 25139371
TI - Structural modification of plasma albumin in sickle cell anemia.
PMID- 25139372
TI - Long-term observation of the vitreomacular relationship in normal fellow eyes of
patients with unilateral idiopathic macular holes.
AB - PURPOSE: To describe long-term changes in the vitreomacular relationship in
normal fellow eyes of patients with unilateral idiopathic macular holes (MHs).
METHODS: This is a retrospective, observational case series. The medical records
of patients who underwent surgery for idiopathic MHs between May 2000 and
December 2010 were reviewed. Patients who had clinically normal fellow eyes and
underwent 12 months or more of follow-up were included. The vitreomacular
relationship in the fellow eyes was evaluated using optical coherence tomography
(OCT) and slit-lamp biomicroscopy. RESULTS: The study included 153 patients with
a mean age of 65.5 years and a mean follow-up of 33.5 months (range, 12-121). The
incidence of vitreomacular attachments evaluated by OCT was 52% (80 eyes) at
initial examination, which decreased to 41, 37 and 23% at 1, 2 and 3 years after
the initial examination, respectively. Of the 80 eyes with vitreomacular
attachments at initial examination, 40 (50%) still had vitreomacular attachments
at the final visit. Of the remaining 40 eyes in which vitreomacular separation
occurred during follow-up, 11 (28%) developed an MH, with a mean interval of 45
months. None of the eyes with vitreomacular separation at presentation developed
an MH. CONCLUSION: This largest series of fellow eyes of MHs followed by OCT
shows that, at presentation, about half of the patients already have premacular
vitreous detachment and therefore no risk of MH, and that second MH develops in
about 30% in the process of vitreomacular separation, which evolves over a
prolonged period.
PMID- 25139373
TI - Results from a secondary data analysis regarding satisfaction with health care
among African American women living with HIV/AIDS.
AB - OBJECTIVE: To analyze satisfaction with health care among African American women
living with HIV/AIDS. DESIGN: Secondary analysis of baseline data of African
American women who participated in Protect and Respect, a sexual risk reduction
program for women living with HIV/AIDS SETTING: HIV Care Clinic in an urban city
in the northeast United States. PARTICIPANTS: One hundred fifty-seven (157)
African American women living with HIV/AIDS. METHODS: Regression analyses were
used to examine the relationships between demographic variables, self-reported
health characteristics, communication with health care providers, and
satisfaction with health care provider. RESULTS: A majority of women reported
satisfaction with medical services (88%, n = 140). Communication with health care
providers, detectable viral load, education, income, self-reported health status,
and sexual orientation were significantly bivariately associated with
satisfaction with healthcare (all ps < .05). In the multivariate models, no
variables significantly predicted satisfaction with healthcare. CONCLUSION:
Because satisfaction with health care can influence the quality of care received,
health outcomes, and adherence to provider recommendations among patients living
with HIV/AIDS, health care providers' ability to elicit satisfaction from their
patients is just as important as the services they provide. This project is one
of the first studies to find high rates of satisfaction with health care among
African American women living with HIV/AIDS. Further examination of satisfaction
with health care among African American women living HIV/AIDS may help in
narrowing health care disparities and negative treatment outcomes.
PMID- 25139374
TI - Globalization and eating disorder risk: peer influence, perceived social norms,
and adolescent disordered eating in Fiji.
AB - OBJECTIVE: The increasing global health burden imposed by eating disorders
warrants close examination of social exposures associated with globalization that
potentially elevate risk during the critical developmental period of adolescence
in low- and middle-income countries (LMICs). The study aim was to investigate the
association of peer influence and perceived social norms with adolescent eating
pathology in Fiji, a LMIC undergoing rapid social change. METHOD: We measured
peer influence on eating concerns (with the Inventory of Peer Influence on Eating
Concerns; IPIEC), perceived peer norms associated with disordered eating and body
concerns, perceived community cultural norms, and individual cultural
orientations in a representative sample of school-going ethnic Fijian adolescent
girls (n = 523). We then developed a multivariable linear regression model to
examine their relation to eating pathology (measured by the Eating Disorder
Examination-Questionnaire; EDE-Q). RESULTS: We found independent and
statistically significant associations between both IPIEC scores and our proxy
for perceived social norms specific to disordered eating (both p < .001) and EDE
Q global scores in a fully adjusted linear regression model. DISCUSSION: Study
findings support the possibility that peer influence as well as perceived social
norms relevant to disordered eating may elevate risk for disordered eating in
Fiji, during the critical developmental period of adolescence. Replication and
extension of these research findings in other populations undergoing rapid social
transition--and where globalization is also influencing local social norms--may
enrich etiologic models and inform strategies to mitigate risk.
PMID- 25139376
TI - Exploration of yttria films as gate dielectrics in sub-50 nm carbon nanotube
field-effect transistors.
AB - Thin yttria films were investigated for use as gate dielectrics in carbon
nanotube field-effect transistors (CNTFETs) with the gate length scaled down to
sub-50 nm size. The yttria film provided an omega-shaped gate dielectric with a
low interface trap density, a low average sub-threshold swing of 74 mV per decade
for both long and short CNTFETs, and a small drain-induced barrier lowering. It
was also shown that the performance of CNTFETs increases with decreasing
temperature, with an excellent sub-threshold swing of 22 mV per decade at liquid
nitrogen temperatures. A method was developed to retrieve the interface trap
density in CNTFETs and a low interface trap density of 5.2 * 10(6) cm(-1) was
achieved, indicating the high electric quality of the yttria films.
PMID- 25139375
TI - Impaired autophagy: a link between neurodegenerative and neuropsychiatric
diseases.
AB - Protein misfolding, and subsequent aggregation have been proven as the leading
cause of most known dementias. Many of these, in addition to neurodegeneration,
show profound changes in behaviour and thinking, thus, psychiatric symptoms. On
the basis of the observation that progressive myoclonic epilepsies and
neurodegenerative diseases share some common features of neurodegeneration, we
proposed autophagy as a possible common impairment in these diseases. Here, we
argue along similar lines for some neuropsychiatric conditions, among them
depression and schizophrenia. We propose that existing and new therapies for
these seemingly different diseases could be augmented with drugs used for
neurodegenerative or neuropsychiatric diseases, respectively, among them some
which modulate or augment autophagy.
PMID- 25139377
TI - Transient tasks and enduring emotions: the impacts of affective content, task
relevance, and picture duration on the sustained late positive potential.
AB - The present experiments were designed to examine the influences of picture
duration, task relevance, and affective content on neural measures of sustained
engagement, as indexed by the late positive potential (LPP). Much prior work has
shown that the event-related potential in and around the P3-here referred to as
the early LPP-is modulated by affective content, nonaffective task relevance, and
stimulus duration. However, later portions of the LPP (>1,000 ms) may represent
either a return to baseline or a continued physiological process related to
motivational engagement. In the present experiments, we tested whether modulation
of the later LPP depends on varying motivational engagement using stimulus
duration, affective content, and task relevance. The results of Experiment 1
revealed that stimulus duration modulates the sustained LPP (i.e., 1,000-2,000
ms) in response to affective, but not task-relevant, stimuli from a modified
counting oddball task. The results of Experiment 2 revealed that the sustained
increase in the LPP is sensitive to both emotional content and task relevance
when the task requires sustained engagement with target stimuli (e.g.,
determining the duration of stimulus presentation). The impacts of emotional
content and task relevance had additive effects on the later portion of the LPP.
In sum, both emotional content and task relevance can result in a protracted
increase in the later LPP. These data suggest that affective content
automatically sustains engagement, whereas task relevance only prolongs
engagement when it is necessary for task completion.
PMID- 25139378
TI - Stability of noble-gas-bound SiH3+ clusters.
AB - The stability of noble gas (Ng)-bound SiH3(+) clusters is explored by ab initio
computations. Owing to a high positive charge (+1.53 e(-)), the Si center of
SiH3(+) can bind two Ng atoms. However, the Si-Ng dissociation energy for the
first Ng atom is considerably larger than that for the second one. As we go down
group 18, the dissociation energy gradually increases, and the largest value is
observed for the case of Rn. For NgSiH3(+) clusters, the Ar-Rn dissociation
processes are endergonic at room temperature. For He and Ne, a much lower
temperature is required for it to be viable. The formation of Ng2SiH3(+) clusters
is also feasible, particularly for the heavier members and at low temperature. To
shed light on the nature of Si-Ng bonding, natural population analysis, Wiberg
bond indices computations, electron-density analysis, and energy-decomposition
analysis were performed. Electron transfer from the Ng centers to the
electropositive Si center occurs only to a small extent for the lighter Ng atoms
and to a somewhat greater extent for the heavier analogues. The Si-Xe/Rn bonds
can be termed covalent bonds, whereas the Si-He/Ne bonds are noncovalent. The Si
Ar/Kr bonds possess some degree of covalent character, as they are borderline
cases. Contributions from polarization and charge transfer and exchange are key
terms in forming Si-Ng bonds. We also studied the effect of substituting the H
atoms of SiH3(+) by halide groups (-X) on the Ng binding ability. SiF3(+) showed
enhanced Ng binding ability, whereas SiCl3(+) and SiBr3(+) showed a lower ability
to bind Ng than SiH3(+). A compromise originates from the dual play of the
inductive effect of the -X groups and X->Si pi backbonding (p(z)-p(z)
interaction).
PMID- 25139379
TI - Use of biosimilars in inflammatory bowel disease: Statements of the Italian Group
for Inflammatory Bowel Disease.
AB - The introduction of biological therapies, particularly anti-TNFalpha agents, has
revolutionized the management of inflammatory bowel disease in those cases which
are refractory to conventional treatment; however these drugs are not risk-free
and their use has substantially increased the cost of treatment. As marketing
protection expires for original, first-generation biopharmaceuticals, lower-cost
"copies" of these drugs produced by competitor companies-referred to as
biosimilars-are already entering the market. In September 2013, the European
Medicines Agency approved two infliximab biosimilars for treatment of adult and
paediatric inflammatory bowel disease patients, a decision based largely on
efficacy and safety data generated in studies of patients with ankylosing
spondylitis and rheumatoid arthritis. For many clinicians, extrapolation
practices and the general question of interchangeability between biosimilars and
reference biologics are cause for concern. In the present paper, the Italian
Group for inflammatory bowel disease presents its statements on these issues,
with emphasis on the peculiar clinical characteristics of inflammatory bowel
disease and the importance of providing physicians and patients with adequate
information and guarantees on the safety and efficacy of these new drugs in the
specific setting of inflammatory bowel disease.
PMID- 25139380
TI - Thymoglobulin induction in kidney transplantation.
PMID- 25139381
TI - Preservation of donor hearts using hypothermic oxygenated perfusion.
AB - BACKGROUND: Hypothermic machine perfusion of donor hearts enables continuous
aerobic metabolism and washout of toxic metabolic byproducts. We evaluated the
effect of machine perfusion on cardiac myocyte integrity in hearts preserved for
4 h in a novel device that provides pulsatile oxygenated hypothermic perfusion
(Paragonix Sherpa PerfusionTM Cardiac Transport System). MATERIAL AND METHODS:
Pig hearts were harvested and stored in Celsior(r) solution for 4 h using either
conventional cold storage on ice (4-h CS, n=6) or the Sherpa device (4-h
pulsatile perfusion (PP), n=6). After cold preservation, hearts were evaluated
using a non-working heart Langendorff system. Controls (n=3) were reperfused
immediately after organ harvest. Biopsies were taken from the apex of the left
ventricle before storage, after storage, and after reperfusion to measure ATP
content and endothelin-1 in the tissue. Ultrastructural analysis using electron
microscopy was performed. RESULTS: Four-hour CS, 4-h PP, and control group did
not show any significant differences in systolic or diastolic function (+dP/dt,
dP/dt, EDP). Four-hour PP hearts showed significantly more weight gain than 4-h
CS after preservation, which shows that machine perfusion led to myocardial
edema. Four-hour CS led to higher endothelin-1 levels after preservation,
suggesting more endothelial dysfunction compared to 4-h PP. Electron microscopy
revealed endothelial cell rupture and damaged muscle fibers in the 4-h CS group
after reperfusion, but the cell structures were preserved in the 4-h PP group.
CONCLUSIONS: Hypothermic pulsatile perfusion of donor hearts leads to a better
preserved cell structure compared to the conventional cold storage method. This
may lead to less risk of primary graft failure after orthotopic heart
transplantation.
PMID- 25139382
TI - A cytoprotective and degradable metal-polyphenol nanoshell for single-cell
encapsulation.
AB - Single-cell encapsulation promises the cytoprotection of the encased cells
against lethal stressors, reminiscent of the sporulation process in nature.
However, the development of a cytocompatible method for chemically mimicking the
germination process (i.e., shell degradation on-demand) has been elusive, despite
the shell degradation being pivotal for the practical use of functional cells as
well as for single cell-based biology. We report that an artificial shell,
composed of tannic acid (TA) and Fe(III) , on individual Saccharomyces cerevisiae
controllably degrades on-demand, while protecting the yeast from multiple
external aggressors, including UV-C irradiation, lytic enzymes, and silver
nanoparticles. Cell division is suppressed by the TA-Fe(III) shell, but restored
fully upon shell degradation. The formation of a TA-Fe(III) shell would provide a
versatile tool for achieving the chemical version of "sporulation and
germination".
PMID- 25139383
TI - Factor structure and gender stability in the multidimensional condom attitudes
scale.
AB - Sexually transmitted infections continue to trouble the United States and can be
attenuated through increased condom use. Attitudes about condoms are an important
multidimensional factor that can affect sexual health choices and have been
successfully measured using the Multidimensional Condom Attitudes Scale (MCAS).
Such attitudes have the potential to vary between men and women, yet little work
has been undertaken to identify if the MCAS accurately captures attitudes without
being influenced by underlying gender biases. We examined the factor structure
and gender invariance on the MCAS using confirmatory factor analysis and item
response theory, within-subscale differential item functioning analyses. More
than 770 participants provided data via the Internet. Results of differential
item functioning analyses identified three items as differentially functioning
between the genders, and removal of these items is recommended. Findings
confirmed the previously hypothesized multidimensional nature of condom attitudes
and the five-factor structure of the MCAS even after the removal of the three
problematic items. In general, comparisons across genders using the MCAS seem
reasonable from a methodological standpoint. Results are discussed in terms of
improving sexual health research and interventions.
PMID- 25139384
TI - A multimodal examination of emotional responding to a trauma-relevant film among
traumatic motor vehicle accident survivors.
AB - The Facial Action Coding System (Ekman & Friesen) has shown promise as a
behavioral measure of emotional experience. The current study examined the degree
of (de)synchrony between self-reported and facial expressions of fear, disgust,
and sadness in response to a traumatic event-relevant film among individuals who
had experienced a traumatic motor vehicle accident. Given high rates of
comorbidity between posttraumatic stress symptoms (PTSS) and depressive symptoms,
the potential impacts of both PTSS and depressive symptoms on emotional
responding were examined. Results demonstrated synchrony between self-reported
and facial expressions of disgust and sadness; however, no association between
measures of fear was observed. Furthermore, depressive symptoms were associated
with greater fear responding and PTSS were associated only with self-reported
fear. Together, results support the importance of examining discrete negative
emotions, rather than broad valence categories, when examining fear-based
responding in traumatic event-exposed populations. Additional research examining
the psychometric properties of the Facial Action Coding System as a measure of
discrete emotional experiences among traumatic event-exposed individuals is
needed to advance multimodal assessment approaches that yield incremental
information for understanding emotional responding in this population.
PMID- 25139385
TI - Oculopalatal tremor: variations on a theme by Guillain and Mollaret.
AB - BACKGROUND: Oculopalatal tremor (OPT) is a delayed complication of a brainstem
lesion, characterized by involuntary contractions of the soft palate associated
with a synchronized ocular pendular nystagmus. MRI reveals inferior olivary
nucleus hypersignal/hypertrophy (IONH). Our objective was to refine the clinical
profile of patients with OPT and to report a few oddities in both presentation
and evolution. METHODS: We performed a retrospective study of patients diagnosed
with OPT and a literature search. RESULTS: From our database, we retrieved 5 men
and 3 women with a diagnosis of OPT. Eighty-two patients with OPT were retrieved
from the literature and were compiled with our series. The average age was 54
years and there was a male predominance. Brainstem vascular lesion was the most
common etiology (80%). Prominent vertical pendular nystagmus was found in 90%.
Dissociated nystagmus was mostly associated to unilateral contralateral IONH on
MRI, while bilateral symmetrical nystagmus was due to a bilateral IONH in the
majority of cases. Three oddities were found amongst our 8 patients: prominent
nystagmus ipsilateral to IONH; disappearance of IONH on MRI despite persisting
nystagmus, and asymptomatic OPT. CONCLUSION: The clinical profile of OPT is
rather stereotyped. Rarely do patients deviate from the classical description of
OPT.
PMID- 25139386
TI - [Medicines for children and "off-label use" 5 years after implementation of the
Paediatric Regulation (EC) No 1901/2006. An interim analyis].
AB - Regulation EC 1901/2006, better known as the "Paediatric Regulation," targets the
challenging aim of improving the supply of pharmaceutical products for children
and adolescents living in Europe. In order to counteract the much-debated and
long-standing problem of "off-label" use within paediatrics, the Paediatric
Regulation established two new paediatric procedures in order to increase the
number of medicines licensed for children in future. This article reports on the
outcomes of these procedures, covering the period from 2007 to the present. The
aim was to find out how many substances underwent the paediatric procedures and
how many medicinal products have been approved explicitly for children as a
result. In the second part, a prioritized off-label analysis was conducted
focusing on the top 100 substances most frequently prescribed to children and
adolescents in Germany in 2011. The top 100 substances consist of the respective
top 20 substances of five therapeutic areas. The prescription scores are based on
the GAmSi project of the National Association of the Statutory Health Insurance
of Germany. The rankings refer to outpatient care and cover the statutory health
insured paediatric population of Germany below 18 years of age, divided into two
age groups, children and adolescents. In order to investigate whether the most
frequently prescribed substances are labelled for paediatric use, 200 SmPCs were
screened and evaluated (cut-off date: 31 December 2012). In a final step, the
relation between the top 100 substances and the Paediatric Regulation was
examined. For this purpose, it was investigated whether the listed substances are
or have been subject to the paediatric procedures in order to identify potential
positive impacts of the Paediatric Regulation.
PMID- 25139388
TI - Advanced kinetic analysis as a tool for formulation development and prediction of
vaccine stability.
AB - We have used a protein-based vaccine, a live virus vaccine, and an experimental
adjuvant to evaluate the utility of an advanced kinetic modeling approach for
stability prediction. The modeling approach uses a systematic and simple
procedure for the selection of the most appropriate kinetic equation to describe
the degradation rate of compounds subjected to accelerated conditions. One-step
and two-step reactions with unlimited combinations of kinetic models were
screened for the three products under evaluation. The most appropriate
mathematical model for a given product was chosen based on the values of residual
sum of squares and the weight parameter w. A relatively simple n-th order kinetic
model best fitted the degradation of an adjuvanted protein vaccine with a
prediction error lower than 10%. A more complex two-step model was required to
describe inactivation of a live virus vaccine under normal and elevated storage
temperatures. Finally, an autocatalytic-type kinetic model best fitted the
degradation of an oil-in-water adjuvant formulation. The modeling approach
described here could be used for vaccine stability prediction, expiry date
estimation, and formulation selection. To the best of our knowledge, this is the
first report describing a global kinetic analysis of degradation of vaccine
components with high prediction accuracy.
PMID- 25139387
TI - Regulation of HPV16 E6 and MCL1 by SF3B1 inhibitor in head and neck cancer cells.
AB - ABT-737 inhibits the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and BCL
X(L). Meayamycin B switches the splicing pattern of myeloid cell leukemia factor
1 (MCL1) pre-mRNA. Specifically, inhibition of splicing factor 3B subunit 1
(SF3B1) with meayamycin B promotes the generation of the proapoptotic, short
splicing variant (MCL1-S) and diminishes the antiapoptotic, long variant (MCL1
L). This action was previously associated with the cytotoxicity of meayamycin B
in non-small cell lung carcinoma cell lines. ABT-737 induced apoptosis in
response to an ablation of MCL1-L by meayamycin B. In this study, we further
exploited this synergistic combination in head and neck squamous cell carcinoma
(HNSCC), up to 90% of which overexpress MCL1 and BCL-X(L). In a panel of seven
HNSCC cell lines, the combination of meayamycin B and ABT-737 rapidly triggered a
Bax/Bak-mediated apoptosis that overcame the resistance from HPV16-positive HNSCC
against each agent alone. Both RT-PCR and Western blotting showed that meayamycin
B up-regulated MCL1-S and down-regulated MCL1-L. Significantly, we discovered
that SF3B1 was involved in the splicing of oncogenic HPV16 E6 to produce non
oncogenic HPV16 E6*, indicating that SF3B1 may inhibit HPV16-induced
tumorigenesis.
PMID- 25139389
TI - Public health implications of obstructive sleep apnea burden.
AB - OBJECTIVE: To assess the implications of obstructive sleep apnea (OSA) burden
among Indian children. METHODS: MonteCarlo simulations were performed in order to
estimate the number of OSA related obesity cases among Indian children (1-14 y of
age) and the number of cases of stroke, coronary heart disease (CHD) and type 2
diabetes, considered as main adverse outcomes of OSA related childhood obesity,
according to untreated and treated [adenotonsillectomy (AT) alone and AT
associated to continuous positive airway pressure (CPAP)] pediatric OSA. Data
used to perform MonteCarlo simulations were derived from a review about current
literature exploring OSA related obesity. RESULTS: The analysis on the number of
adverse outcomes according to treated and untreated obesity related to OSA showed
that treatments reduce the number of obesity cases, resulting in a great
reduction of the amount of stroke, CHD and type 2 diabetes cases. However, the
cost for treating adverse outcome was higher in patients treated for obesity
related to OSA compared to those not receiving any treatment. CONCLUSIONS: The
reduction in the number of adverse outcomes due to treatment of obesity related
OSA implicates the urgent need for public health policies in providing screening
for OSA among children population: an early detection and a consequently prompt
reaction to pediatric OSA could improve the burden of OSA related obesity.
PMID- 25139390
TI - Cross-regional analysis of multiple factors associated with childhood obesity in
India: a national or local challenge?
AB - OBJECTIVE: To investigate obesogenic co-causing factors, promoting rise of weight
in children, associated to local differences in India. METHODS: Overall 1,680
children, aged 3-11 and balanced by gender, were recruited in school contexts
distributed in seven major Indian cities. All children were weighted and measured
in order to calculate their BMI. A validated cultural specific questionnaire was
administered to children's parents for assessing socio-demographic data, eating
habits, physical activity, etc. Furthermore children's brand awareness scores
were computed in order to analyze their affiliation towards food-based
advertisement. Descriptive statistics of frequencies, duration and intensity of
the various factors were performed. Chi-square tests or Wilcoxon signed rank test
were used for evaluating significance of differences in factors distribution
across Indian cities. RESULTS: Four factors, promoting rise of children's weight,
were individuated as associated to urban differences, namely meal times consumed
in the family, parents' BMI, brand awareness and physical activity. These aspects
exercised a significant impact on children's body size in Kolkata and Chennai.
Hyderabad and Mumbai, instead, were the cities where religion played some role in
influencing children's weight gain. CONCLUSIONS: Such findings underline the need
to frame obesity as a situated phenomenon rather than a national problem. Health
policies, implemented in treating and preventing obesity, should be therefore
specifically focused on locally situated peculiarities.
PMID- 25139391
TI - 18-Electron rule inspired Zintl-like ions composed of all transition metals.
AB - Zintl phase compounds constitute a unique class of compounds composed of metal
cations and covalently bonded multiply charged cluster anions. Potential
applications of these materials in solution chemistry and thermoelectric
materials have given rise to renewed interest in the search for new Zintl ions.
Up to now these ions have been mostly composed of group 13, 14, and 15 post
transition metal elements and no Zintl ions composed of all transition metal
elements are known. Using gradient corrected density functional theory we show
that the 18-electron rule can be applied to design a new class of Zintl-like ions
composed of all transition metal atoms. We demonstrate this possibility by using
Ti@Au12(2-) and Ni@Au6(2-) di-anions as examples of Zintl-like ions. Predictive
capability of our approach is demonstrated by showing that FeH6(4-) in an already
synthesized complex metal hydride, Mg2FeH6, is a Zintl-like ion, satisfying the
18-electron rule. We also show that novel Zintl phase compounds can be formed by
using all transition metal Zintl-like ions as building blocks. For example, a two
dimensional periodic structure of Na2[Ti@Au12] is semiconducting and nonmagnetic
while a one-dimensional periodic structure of Mg[Ti@Au12] is metallic and
ferromagnetic. Our results open the door to the design and synthesis of a new
class of Zintl-like ions and compounds with potential for applications.
PMID- 25139392
TI - Synthesis of novel two-phase Co@SiO2 nanorattles with high catalytic activity.
AB - Noble metal nanocatalysts with remarkable catalytic properties have attracted
much attention; however, the high cost of these materials limits their industrial
applications. Here, we design and prepare Co@SiO2 nanorattles as a mixture of hcp
Co and fcc-Co phases as a substitute. The nanorattles exhibit both superior
catalytic activity and high stability for the reduction of p-nitrophenol. The
reduction rate nearly follows pseudo-first-order kinetics, and the reaction rate
constant is as high as 0.815 min(-1) and is maintained at 0.565 min(-1) even
after storing for one month, which is higher than that reported for noble metal
nanocatalysts. Such an excellent property can be attributed to the novel two
phase composition and rattle-type structure.
PMID- 25139393
TI - The prevalence and distribution of gastrointestinal parasites of stray and refuge
dogs in four locations in India.
AB - A gastrointestinal parasite survey of 411 stray and refuge dogs sampled from four
geographical and climactically distinct locations in India revealed these animals
to represent a significant source of environmental contamination for parasites
that pose a zoonotic risk to the public. Hookworms were the most commonly
identified parasite in dogs in Sikkim (71.3%), Mumbai (48.8%) and Delhi (39.1%).
In Ladakh, which experiences harsh extremes in climate, a competitive advantage
was observed for parasites such as Sarcocystis spp. (44.2%), Taenia hydatigena
(30.3%) and Echinococcus granulosus (2.3%) that utilise intermediate hosts for
the completion of their life cycle. PCR identified Ancylostoma ceylanicum and
Ancylostoma caninum to occur sympatrically, either as single or mixed infections
in Sikkim (Northeast) and Mumbai (West). In Delhi, A. caninum was the only
species identified in dogs, probably owing to its ability to evade unfavourable
climatic conditions by undergoing arrested development in host tissue. The
expansion of the known distribution of A. ceylanicum to the west, as far as
Mumbai, justifies the renewed interest in this emerging zoonosis and advocates
for its surveillance in future human parasite surveys. Of interest was the
absence of Trichuris vulpis in dogs, in support of previous canine surveys in
India. This study advocates the continuation of birth control programmes in stray
dogs that will undoubtedly have spill-over effects on reducing the levels of
environmental contamination with parasite stages. In particular, owners of pet
animals exposed to these environments must be extra vigilant in ensuring their
animals are regularly dewormed and maintaining strict standards of household and
personal hygiene.
PMID- 25139394
TI - Frequency evaluation of different extraction protocols in orthodontic treatment
during 35 years.
AB - BACKGROUND: Studies that show frequencies of different orthodontic treatment
protocols can be used as valuable parameters in the interpretation of treatment
tendency with time. The purpose of this retrospective study was to evaluate all
orthodontic treatment planning conducted at the Orthodontic Department at Bauru
Dental School, University of Sao Paulo, Brazil, since 1973, in order to
investigate extraction and non-extraction protocol frequencies selected at each
considered period. METHODS: The sample comprised 3,413 records of treated
patients and was evaluated according to the protocol choice, divided into 10
groups: Protocol 0 (non-extraction); Protocol 1 (four first premolar
extractions); Protocol 2 (two first maxillary and two second mandibular
premolars); Protocol 3 (two maxillary premolar extractions); Protocol 4 (four
second premolars); Protocol 5 (asymmetric premolar extractions); Protocol 6
(incisor or canine extractions); Protocol 7 (first or second molar extractions);
Protocol 8 (atypical extractions) and Protocol 9 (agenesis and previously missing
permanent teeth). These protocols were evaluated in seven 5-year intervals:
Interval 1 (1973 to 1977); Interval 2 (1978 to 1982); Interval 3 (1983 to 1987);
Interval 4 (1988 to 1992); Interval 5 (1993 to 1997); Interval 6 (1998 to 2002);
Interval 7 (2003 to 2007). The frequency of each protocol was compared between
the seven intervals, using the proportion test (P < 0.05). RESULTS: The results
showed that 10 protocol frequencies were significantly different among the 7 time
intervals. CONCLUSIONS: The non-extraction protocol frequency increased gradually
with consequent reduction of extraction treatments. The four premolar extraction
protocol frequency decreased gradually while the two maxillary premolar
extraction protocol has maintained the same frequency of indications throughout
time.
PMID- 25139395
TI - Small-molecule survivin inhibitor YM155 enhances radiosensitization in esophageal
squamous cell carcinoma by the abrogation of G2 checkpoint and suppression of
homologous recombination repair.
AB - BACKGROUND: Survivin is overexpressed in cancer cells and plays a crucial role in
apoptosis evasion. YM155, a small-molecule inhibitor of survivin, could enhance
the cytotoxicity of various DNA-damaging agents. Here, we evaluated the
radiosensitizaion potential of YM155 in human esophageal squamous cell carcinoma
(ESCC). METHODS: Cell viability was determined by CCK8 assay. The
radiosensitization effect of YM155 was evaluated by clonogenic survival and
progression of tumor xenograft. Cell cycle progression was determined by flow
cytometric analysis. Radiation-induced DNA double strand break (DSB) and
homologous recombination repair (HRR) were detected by the staining of gamma-H2AX
and RAD51, respectively. Expression of survivin and cell cycle regulators was
detected by Western blot analysis. RESULTS: YM155 induced radiosensitization in
ESCC cell lines Eca109 and TE13, associated with the abrogation of radiation
induced G2/M checkpoint, impaired Rad51 focus formation, and the prolongation of
gamma-H2AX signaling. G2/M transition markers, including the activation of
cyclinB1/Cdc2 kinase and the suppression of Cdc2 Thr14/Tyr15 phosphorylation were
induced by YM155 in irradiated cells. The combination of YM155 plus irradiation
delayed the growth of ESCC tumor xenografts to a greater extent compared with
either treatment modality alone. CONCLUSIONS: Our findings suggest that the
abrogation of G2 checkpoint and the inhibition of HRR contribute to
radiosensitization by YM155 in ESCC cells.
PMID- 25139396
TI - Anthocyanins as a potential therapy for diabetic retinopathy.
AB - Diabetic retinopathy is one of the most common complications of diabetes. A
plethora of literature indicates that oxidative stress may play a central role in
the pathogenesis of diabetic retinopathy. One could thus hypothesise that
antioxidant therapies may be protective for diabetic retinopathy. Anthocyanins
are important natural bioactive pigments responsible for red-blue colour of
fruits, leaves, seeds, stems and flowers in a variety of plant species. Apart
from their colours, anthocyanins are known to be health-promoting phytochemicals
with potential properties useful to protect against oxidative stress in some
degenerative diseases. They also have a variety of biological properties
including anti-inflammatory, antibacterial, anticancer, and cardio-protective
properties. Some reports further suggest a therapeutic role of anthocyanins to
prevent and/or protect against ocular diseases but more studies are needed to
examine their potential as alternative therapy to diabetic retinopathy. The
present article reviews the available literature concerning the beneficial role
of anthocyanins in diabetic retinopathy.
PMID- 25139397
TI - Primary Urothelial Carcinoma of the Prostate with Glandular Differentiation: A
Case Report.
AB - A 53-year-old man presented to our department with acute urinary retention and an
approximate 8-year history of frequent urination, dysuria, poor urinary stream
and nocturia. His prostate-specific antigen (PSA) values were normal (<4 ng/ml)
upon repeated testing. The patient was diagnosed with benign prostatic
hyperplasia, although there was no significant improvement in his symptoms after
treatment with oral finasteride and doxazosin. He then underwent transurethral
resection of the prostate in February 2013, and histopathological examination
showed adenocarcinoma of the prostate. His treatment regimen included daily oral
bicalutamide and subcutaneous injection of Zoladex once per month. Three months
later, radical prostatectomy was performed, and a prostate histopathological
examination indicated primary urothelial carcinoma with glandular
differentiation. His PSA values were normal (<4 ng/ml) before and after the
radical prostatectomy. After the second operation, the patient received
chemotherapy with gemcitabine and cisplatin. Two months later, magnetic resonance
imaging (MRI) indicated local tumor recurrence. The patient was treated with
chemotherapy combined with radiotherapy for 2 months, and subsequent MRI results
showed that the recurrent tumor volume was significantly reduced. As a result,
radiotherapy was stopped. The patient remains alive, and his general condition
has clearly improved.
PMID- 25139398
TI - Prognostic factors for patients with atypical or malignant meningiomas treated at
a single center.
AB - The purpose of this study is to summarize our experience in managing patients
with an atypical or malignant meningioma at our institution, with a specific
focus on determining the prognostic factors for treatment outcome. We reviewed
the records of 126 patients with atypical or malignant meningiomas from January
2001 to August 2011. Data collected included gender, age, Karnofsky Performance
Scale (KPS) score, pathology results, cleavability, and bone invasion. The
symptoms and signs were recorded for further outcome analysis. There were 37
malignant meningiomas and 89 atypical meningiomas. Total resection (Simpson grade
I-II) was achieved in 80.9% of atypical patients (n = 72) and 67.6% of malignant
patients (n = 25). Forty patients (44.9%) in the atypical group underwent
radiotherapy after surgery, while 26 (70.2%) patients underwent radiotherapy in
the malignant group. The median follow-up duration was 25 months. Patients with a
secondary tumor had a much shorter progression-free survival (PFS) than those
with a primary tumor in the malignant group. The malignant meningioma group had
lower overall survival. Progression-free survival for patients in the malignant
group who received postoperative radiotherapy was longer than that for those who
did not receive radiotherapy. In conclusion, total resection of the tumor was
important because patients with a secondary tumor were much more likely to have
recurrence than patients with a primary tumor in the atypical and malignant
meningioma groups. Also, radiotherapy should be performed after surgery for a
malignant meningioma.
PMID- 25139399
TI - Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances
the effects of a statin.
AB - Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a potential
novel strategy for treatment of CVD. Alirocumab is a fully human PCSK9 monoclonal
antibody in phase 3 clinical development. We evaluated the antiatherogenic
potential of alirocumab in APOE*3Leiden.CETP mice. Mice received a Western-type
diet and were treated with alirocumab (3 or 10 mg/kg, weekly subcutaneous dosing)
alone and in combination with atorvastatin (3.6 mg/kg/d) for 18 weeks. Alirocumab
alone dose-dependently decreased total cholesterol (-37%; -46%, P < 0.001) and
TGs (-36%; -39%, P < 0.001) and further decreased cholesterol in combination with
atorvastatin (-48%; -58%, P < 0.001). Alirocumab increased hepatic LDL receptor
protein levels but did not affect hepatic cholesterol and TG content. Fecal
output of bile acids and neutral sterols was not changed. Alirocumab dose
dependently decreased atherosclerotic lesion size (-71%; -88%, P < 0.001) and
severity and enhanced these effects when added to atorvastatin (-89%; -98%, P <
0.001). Alirocumab reduced monocyte recruitment and improved the lesion
composition by increasing the smooth muscle cell and collagen content and
decreasing the macrophage and necrotic core content. Alirocumab dose-dependently
decreases plasma lipids and, as a result, atherosclerosis development, and it
enhances the beneficial effects of atorvastatin in APOE*3Leiden.CETP mice. In
addition, alirocumab improves plaque morphology.
PMID- 25139400
TI - Docosahexaenoic acid supplementation modifies fatty acid incorporation in tissues
and prevents hypoxia induced-atherosclerosis progression in apolipoprotein-E
deficient mice.
AB - The n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), displays anti
inflammatory properties that may prevent atherosclerosis progression. Exposure of
apolipoprotein-E deficient (ApoE(-/-)) mice to chronic intermittent hypoxia (CIH)
accelerates atherosclerosis progression. Our aim was to assess DHA
supplementation influence on fatty acid incorporation in different tissues/organs
and on atherosclerosis progression in ApoE(-/-) mice exposed to CIH. ApoE(-/-)
mice were exposed to CIH or normoxia (N) and randomized to four groups (N
control, CIH control, N+DHA, and CIH+DHA). DHA-supplementation enhanced DHA and
reduced arachidonic acid (AA) contents in tissues/organs. CIH control mice
exhibited increased atherosclerosis lesion sizes compared to N control mice. DHA
prevented CIH induced atherosclerosis but did not improve atherosclerosis burden
in N mice. Aortic matrix metalloproteinase-2 (MMP-2) expression was decreased in
CIH+DHA mice (p=0.007). DHA-supplementation prevented CIH-induced atherosclerosis
acceleration. This was associated with a decrease of AA incorporation and of
aortic MMP-2 gene expression.
PMID- 25139401
TI - High blood oxygen affinity in the air-breathing swamp eel Monopterus albus.
AB - The Asian swamp eel (Monopterus albus, Zuiew 1793) is a facultative air-breathing
fish with reduced gills. Previous studies have shown that gas exchange seems to
occur across the epithelium of the buccopharyngeal cavity, the esophagus and the
integument, resulting in substantial diffusion limitations that must be
compensated by adaptations in others steps of the O2 transport system to secure
adequate O2 delivery to the respiring tissues. We therefore investigated O2
binding properties of whole blood, stripped hemoglobin (Hb), two major isoHb
components and the myoglobin (Mb) from M. albus. Whole blood was sampled using
indwelling catheters for blood gas analysis and determination of O2 equilibrium
curves. Hb was purified to assess the effects of endogenous allosteric effectors,
and Mb was isolated from heart and skeletal muscle to determine its O2 binding
properties. The blood of M. albus has a high O2 carrying capacity [hematocrit
(Hct) of 42.4+/-4.5%] and binds O2 with an unusually high affinity (P50=2.8+/
0.4mmHg at 27 degrees C and pH7.7), correlating with insensitivity of the Hb to
the anionic allosteric effectors that normally decrease Hb-O2 affinity. In
addition, Mb is present at high concentrations in both heart and muscle (5.16+/
0.99 and 1.08+/-0.19mg ? g wet tissue-1, respectively). We suggest that the high
Hct and high blood O2 affinity serve to overcome the low diffusion capacity in
the relatively inefficient respiratory surfaces, while high Hct and Mb
concentration aid in increasing the O2 flux from the blood to the muscles.
PMID- 25139402
TI - Cold hardiness and deacclimation of overwintering Papilio zelicaon pupae.
AB - Seasonally-acquired cold tolerance can be reversed at warm temperatures, leaving
temperate ectotherms vulnerable to cold snaps. However, deacclimation, and its
underlying mechanisms, has not been well-explored in insects. Swallowtail
butterflies are widely distributed but in some cases their range is limited by
low temperature and their cold tolerance is seasonally acquired, implying that
they experience mortality resulting from deacclimation. We investigated cold
tolerance and hemolymph composition of Anise swallowtail (Papilio zelicaon) pupae
during overwintering in the laboratory, and after four days exposure to warm
temperatures in spring. Overwintering pupae had supercooling points around -20.5
degrees C and survived brief exposures to -30 degrees C, suggesting partial
freeze tolerance. Overwintering pupae had hemolymph osmolality of approximately
920 mOsm, imparted by high concentrations of glycerol, K+ and Na+. After exposure
to spring warming, supercooling points increased to approximately -17 degrees C,
and survival of a 1h exposure to -20 degrees C decreased from 100% to 0%. This
deacclimation was associated with decreased hemolymph osmolality and reduced
glycerol, trehalose, Na+ and Ca2+ concentrations. We compared cold tolerance of
pupae to weather conditions at and beyond the species' northern range boundary.
Minimum temperatures at the range boundary approached the lower lethal
temperature of pupae, and were colder north of the range, suggesting that cold
hardiness may set northern range limits. Minimum temperatures following warm
snaps were likely to cause mortality in at least one of the past three years.
Cold snaps in the spring are increasing in frequency as a result of global
climate change, so are likely to be a significant source of mortality for this
species, and other temperate ectotherms.
PMID- 25139403
TI - The role of rosiglitazone in the proliferation of vascular smooth muscle cells
after experimental subarachnoid hemorrhage.
AB - BACKGROUND: Recent evidence has demonstrated that rosiglitazone can attenuate
cerebral vasospasm following subarachnoid hemorrhage (SAH). Some studies have
shown that rosiglitazone can suppress inflammation and immune responses after
SAH. However, the precise molecular mechanisms by which cerebral vasospasm is
attenuated is not clear. METHODS: In this study, SAH was created using a "double
hemorrhage" injection rat model. Rats were randomly divided into three groups and
treated with saline (control group), untreated (SAH group), or treated with
rosiglitazone. Using immunocytochemistry, hematoxylin and eosin (HE) staining,
and measurement of the basilar artery, we investigated the formation of
pathologic changes in the basilar artery, measured the expression of caveolin-1
and proliferating cell nuclear antigen (PCNA), and investigated the role of
rosiglitazone in vascular smooth muscle cell (VSMC) proliferation in the basilar
artery after SAH. RESULTS: In this study, we observed significant pathologic
changes in the basilar artery after experimental SAH. The level of vasospasm
gradually increased with time during the 1st week, peaked on day 7, and almost
recovered on day 14. After rosiglitazone treatment, the level of vasospasm was
significantly attenuated in comparison with the SAH group. Immunocytochemistry
staining showed that caveolin-1 expression was significantly increased in the
rosiglitazone group, compared with the SAH group. Inversely, the expression of
PCNA showed a notable decrease after rosiglitazone treatment. CONCLUSIONS: The
results indicate that rosiglitazone can attenuate cerebral vasospasm following
SAH. Up-regulation of caveolin-1 by rosiglitazone may be a new molecular
mechanism for this response, which is to inhibit proliferation of VSMCs after
SAH, and this study may provide a novel insight to prevent delayed cerebral
vasospasm (DCVS).
PMID- 25139404
TI - Phosphatase of regenerating liver-3 is regulated by signal transducer and
activator of transcription 3 in acute myeloid leukemia.
AB - Overexpression of protein-tyrosine phosphatase of regenerating liver 3 (PRL-3)
has been identified in about 50% of patients with acute myeloid leukemia (AML).
The mechanism of regulation of PRL-3 remains obscure. Signal transducer and
activator of transcription 3 (STAT3), a latent transcriptional factor, has also
been often found to be activated in AML. We first identified STAT3-consensus
binding sites in the promoter of PRL-3 genes. Then we experimentally validated
the direct binding and transcriptional activation. We applied shRNA-mediated
knockdown and overexpression approaches in STAT3(-/-) liver cells and leukemic
cells to validate the functional regulation of PRL-3 by STAT3. A STAT3 core
signature, derived through data mining from publicly available gene expression
data, was employed to correlate PRL-3 expression in large AML patient samples. We
discovered that STAT3 binds to the -201 to -210 region of PRL-3, which was
conserved between human and mouse. Importantly, PRL-3 protein was significantly
reduced in mouse STAT3-knockout liver cells compared with STAT3-wild type
counterparts, and ectopic expression of STAT3 in these cells led to a pronounced
increase in PRL-3 protein. We demonstrated that STAT3 functionally regulated PRL
3, and STAT3 core signature was enriched in AML with high PRL-3 expression.
Targeting either STAT3 or PRL-3 reduced leukemic cell viability. Silencing PRL-3
impaired invasiveness and induced leukemic cell differentiation. In conclusion,
PRL-3 was transcriptionally regulated by STAT3. The STAT3/PRL-3 regulatory loop
contributes to the pathogenesis of AML, and it might represent an attractive
therapeutic target for antileukemic therapy.
PMID- 25139405
TI - A trans-outer membrane porin-cytochrome protein complex for extracellular
electron transfer by Geobacter sulfurreducens PCA.
AB - The multi-heme, outer membrane c-type cytochrome (c-Cyt) OmcB of Geobacter
sulfurreducens was previously proposed to mediate electron transfer across the
outer membrane. However, the underlying mechanism has remained uncharacterized.
In G. sulfurreducens, the omcB gene is part of two tandem four-gene clusters,
each is predicted to encode a transcriptional factor (OrfR/OrfS), a porin-like
outer membrane protein (OmbB/OmbC), a periplasmic c-type cytochrome (OmaB/OmaC)
and an outer membrane c-Cyt (OmcB/OmcC) respectively. Here, we showed that
OmbB/OmbC, OmaB/OmaC and OmcB/OmcC of G. sulfurreducens PCA formed the porin
cytochrome (Pcc) protein complexes, which were involved in transferring electrons
across the outer membrane. The isolated Pcc protein complexes reconstituted in
proteoliposomes transferred electrons from reduced methyl viologen across the
lipid bilayer of liposomes to Fe(III)-citrate and ferrihydrite. The pcc clusters
were found in all eight sequenced Geobacter and 11 other bacterial genomes from
six different phyla, demonstrating a widespread distribution of Pcc protein
complexes in phylogenetically diverse bacteria. Deletion of ombB-omaB-omcB-orfS
ombC-omaC-omcC gene clusters had no impact on the growth of G. sulfurreducens PCA
with fumarate but diminished the ability of G. sulfurreducens PCA to reduce
Fe(III)-citrate and ferrihydrite. Complementation with the ombB-omaB-omcB gene
cluster restored the ability of G. sulfurreducens PCA to reduce Fe(III)-citrate
and ferrihydrite.
PMID- 25139406
TI - Therapeutic decision making in patients with newly diagnosed low grade glioma.
AB - OPINION STATEMENT: Low grade gliomas (LGG) encompass primary brain tumors that
are typically well-differentiated and do not exhibit frankly malignant histologic
features. These tumors can be further classified by their cellular morphology
(eg, oligodendroglioma, pilocytic astrocytoma, etc), which does convey prognostic
and therapeutic implications. Typically, low grade gliomas convey an overall
better prognosis for patients as opposed to the higher grade primary brain
tumors. Surgery for low grade gliomas and timing of such intervention remains
controversial. Maximal resection of these tumors appears to prolong progression
free survival. Advanced surgical techniques, including language mapping and awake
craniotomies, have been shown to decrease morbidity associated with resection of
lesions in eloquent areas of the brain. Radiation therapy has been proven
effective in increasing time to progression in LGG, and emerging data support a
role for combined modality therapy incorporating chemotherapy. Postoperative RT
has been shown to have significant benefits with regards to progression free
survival. Recent advances in molecular genetic markers, including the combined
loss of chromosome arms 1p and 19q, and the mutation of the isocitrate
dehydrogenase gene (IDH1/IDH2) have allowed for increased accuracy of predicting
susceptibility to chemotherapeutic agents, as well as having some role in
determining prognosis. PCV and temozolomide chemotherapy have both been studied
when assessing progression free survival for LGG patients. Approaching patients
with LGGs can be somewhat daunting given the lack of Class I evidence based
protocols. However, significant evidence is now mounting to suggest early,
maximal surgical excision; followed by fractionated RT will be the mainstays of
treatment. Clearly, additional evidence is also mounting for the addition of
chemotherapy in the treatment paradigm for patients with LGGs.
PMID- 25139407
TI - Microbial signature profiles of periodontally healthy and diseased patients.
AB - AIM: To determine microbial profiles that discriminate periodontal health from
different forms of periodontal diseases. METHODS: Subgingival biofilm was
obtained from patients with periodontal health (27), gingivitis (11), chronic
periodontitis (35) and aggressive periodontitis (24), and analysed for the
presence of >250 species/phylotypes using HOMIM. Microbial differences among
groups were examined by Mann-Whitney U-test. Regression analyses were performed
to determine microbial risk indicators of disease. RESULTS: Putative and
potential new periodontal pathogens were more prevalent in subjects with
periodontal diseases than periodontal health. Detection of Porphyromonas
endodontalis/Porphyromonas spp. (OR 9.5 [1.2-73.1]) and Tannerella forsythia (OR
38.2 [3.2-450.6]), and absence of Neisseria polysaccharea (OR 0.004 [0-0.15]) and
Prevotella denticola (OR 0.014 [0-0.49], p < 0.05) were risk indicators of
periodontal disease. Presence of Aggregatibacter actinomycetemcomitans (OR 29.4
[3.4-176.5]), Cardiobacterium hominis (OR 14.9 [2.3-98.7]), Peptostreptococcaceae
sp. (OR 35.9 [2.7-483.9]), P. alactolyticus (OR 31.3 [2.1-477.2]), and absence of
Fretibacterium spp. (OR 0.024 [0.002-0.357]), Fusobacterium
naviforme/Fusobacterium nucleatum ss vincentii (OR 0.015 [0.001-0.223]),
Granulicatella adiacens/Granulicatella elegans (OR 0.013 [0.001-0.233], p < 0.05)
were associated with aggressive periodontitis. CONCLUSION: There were specific
microbial signatures of the subgingival biofilm that were able to distinguish
between microbiomes of periodontal health and diseases. Such profiles may be used
to establish risk of disease.
PMID- 25139408
TI - Arabidopsis thaliana IRX10 and two related proteins from psyllium and
Physcomitrella patens are xylan xylosyltransferases.
AB - The enzymatic mechanism that governs the synthesis of the xylan backbone polymer,
a linear chain of xylose residues connected by beta-1,4 glycosidic linkages, has
remained elusive. Xylan is a major constituent of many kinds of plant cell walls,
and genetic studies have identified multiple genes that affect xylan formation.
In this study, we investigate several homologs of one of these previously
identified xylan-related genes, IRX10 from Arabidopsis thaliana, by heterologous
expression and in vitro xylan xylosyltransferase assay. We find that an IRX10
homolog from the moss Physcomitrella patens displays robust activity, and we show
that the xylosidic linkage formed is a beta-1,4 linkage, establishing this
protein as a xylan beta-1,4-xylosyltransferase. We also find lower but
reproducible xylan xylosyltransferase activity with A. thaliana IRX10 and with a
homolog from the dicot plant Plantago ovata, showing that xylan
xylosyltransferase activity is conserved over large evolutionary distance for
these proteins.
PMID- 25139409
TI - ?
PMID- 25139410
TI - Burden of carbapenem-resistant organisms in the Frankfurt/Main Metropolitan Area
in Germany 2012/2013 - first results and experiences after the introduction of
legally mandated reporting.
AB - BACKGROUND: The federal state of Hesse, Germany, introduced a laboratory-based
reporting scheme for carbapenem-resistant organisms (CROs). METHOD: The results
of the first year of mandated reporting of CROs from April 2012 through March
2013 to the Public Health Authority of Frankfurt/Main, responsible for a
population of 700,000 inhabitants, are described. RESULTS: Within a period of 12
months 243 CROs were notified to the health authority. Of these 213 isolates had
been reported from 16 of the 17 hospitals in Frankfurt/Main, 6 from ambulatory
settings and 24 from clinics outside of Frankfurt/Main. Mean incidence rate per
1,000 patient days in hospitals was 0.138 (range 0.02-0.28). CONCLUSION: In
Frankfurt/Main almost all hospitals have reported CROs in the study period though
the frequency of isolation varies strongly and many facilities only report CROs
sporadically. Molecular data indicate a high diversity of different
carbapenemases. Autochthonous transmission must be assumed despite the absence of
major outbreaks. Rapid and coordinated efforts by clinicians and health
departments are crucial to control the spread of CRO infections. The mandatory
reporting scheme provides important data to guide the implementation of
preventive measures.
PMID- 25139411
TI - Immediate hypersensitivity reaction following liposomal amphotericin-B (AmBisome)
infusion.
AB - Liposomal amphotericin-B (AmBisome) is now becoming first choice for the
treatment of visceral leishmaniasis (kala-azar) patients due to high efficacy and
less toxicity. The reported incidence of hypersensitivity reactions to liposomal
amphotericin-B (AmBisome), especially during therapy, is very rare. We report two
patients with kala-azar: one developed breathing difficulties and hypotension
followed by shock and the other had facial angioedema with chest tightness during
treatment. Both patients were managed with immediate action of injection:
adrenaline, diphenhydramine and hydrocortisone. In our experience, AmBisome can
cause severe hypersensitivity reactions that warrant proper support and close
supervision.
PMID- 25139412
TI - Use of long-acting reversible contraceptives in the UK from 2004 to 2010:
analysis using The Health Improvement Network Database.
AB - OBJECTIVES: To determine the use of long-acting reversible contraceptives (LARCs)
in the UK over the period 2004 to 2010, using the general practice database The
Health Improvement Network (THIN). METHODS: Women in THIN, aged 18 to 44 years
during 2004 to 2010, who had been registered with their general practitioner for
at least five years, with a prescription history of at least one year were
included. THIN was searched using the Read and MULTILEX codes for: copper
intrauterine devices (Cu-IUDs), the levonorgestrel releasing-intrauterine system
(LNG-IUS), progestogen-only implants, and progestogen-only injections. RESULTS:
The prevalence of progestogen-only implant use rose from 0.5 to 3.4%, and that of
the LNG-IUS from 3.1 to 5.2%. The annual incidence and prevalence of progestogen
only implant use increased for all age groups but was most marked in younger
women, whereas the use of the LNG-IUS augmented with increasing age. For all
women, there was a small decrease in the prevalence of use of Cu-IUDs (from 5.4
to 4.8%) and progestogen-only injections (from 3.6 to 3.2%). CONCLUSIONS: Uptake
of progestogen-only implants and the LNG-IUS increased over the period 2004 to
2010 in the UK, but LARC use in young women remains low.
PMID- 25139413
TI - PTEN loss-mediated Akt activation increases the properties of cancer stem-like
cell populations in prostate cancer.
AB - OBJECTIVE: To demonstrate that the PTEN/PI3K/Akt/NF-kappaB pathway plays an
important role in regulating the prostate cancer stem-like cell population by
upregulating ABCG2. METHODS: Targeted PTEN knockdown in human prostate DU145 and
22Rv1 cells using a small interfering RNA were confirmed by immunoblot analysis
using antibodies of PTEN, phospho-Akt, Akt, and alpha-tubulin. Knockdown PTEN
DU145 and 22Rv1 cells were augmented, and the stem cell-like properties were
examined by cell viability and tumor sphere formation and treated by Akt IV
inhibitor to provide the signal transduction pathway. Luciferase activity assays
were performed. RESULTS: The knockdown of PTEN in prostate cancer cell lines
increased the stem-like properties of the cells, including their sphere-forming
ability, stem cell population number, epithelial-mesenchymal transition-related
gene expression, and ABCG2 expression. Additionally, PTEN expression was highly
associated with elevated expression of phospho-Akt. Treatment with an Akt
inhibitor suppressed the PTEN-mediated effects on the properties of these stem
like cells as well as drug resistance, ABCG2 expression, and the NF-kappaB
pathway. CONCLUSION: The loss of PTEN in prostate cancer cells resulted in an
increased PI3K/Akt pathway. Due to the Akt activation, PTEN loss may play an
important role in prostate cancer by promoting cancer stemness through a
mechanism that involves enhanced NF-kappaB signaling.
PMID- 25139414
TI - Etiology, clinical features and management of acute recurrent pancreatitis.
AB - OBJECTIVE: To study the etiology and clinical features of acute recurrent
pancreatitis (ARP) and to determine its optimal management and outcomes. METHODS:
ARP cases among acute pancreatitis patients who were admitted to the West China
Hospital, Sichuan University from January 2008 to December 2012 were
retrospectively collected. Their etiology, clinical features, treatments and
outcomes were analyzed. RESULTS: Of all pancreatitis patients, 8.9% were
classified as ARP. The proportions of mild and severe diseases were 85.7% and
14.3%, respectively. The common etiological factors were biliogenic (31.0%),
alcohol (26.2%), hyperlipidemia (21.4%) and pancreaticobiliary malformation
(15.4%). At first 46 cases were cryptogenic and among them 36 were subsequently
confirmed by endoscopic retrograde cholangiopancreatography (ERCP). Among the
hyperlipidemic ARP patients, 72.2% failed to routinely monitor and control serum
lipids. ERCP was performed in 88 cases, and 48 also required an endoscopic
sphincterotomy or calculus removal. Twenty-two patients underwent
cholangiopancreatic duct stent placement, and pancreatic necrosectomy was
performed on eight severe cases. The overall outcomes indicate that 8.3% of the
cases progressed to chronic pancreatitis and 33.3% of the cases receiving
etiological treatment were recurrence-free. There were no deaths in this study.
CONCLUSIONS: The etiological factors of ARP are similar to those of acute
pancreatitis at the first attack. The management of ARP should be fully
considered based on etiological investigation.
PMID- 25139415
TI - Basosquamous carcinoma: is it an aggressive tumor?
AB - Basosquamous carcinoma is a rare cutaneous tumour that is considered an
aggressive type of basal cell carcinoma with an increased risk of recurrence and
metastases. This impression has been perpetuated in the literature, despite
limited scientific data and conflicting results of some authors. This present
study was aimed to evaluate the clinical-pathological features of this tumour and
follow-up of a series of basosquamous carcinoma. Basosquamous carcinoma patients
who underwent surgical excision between January 2000 and February 2012 were
analyzed retrospectively. Their medical files were reviewed and the corresponding
routinely stained sections (with hematoxylin-eosin) were re-evaluated by two
pathologists. Thirty-five patients with basosquamous carcinoma were operated on
in this period. Most tumurs were located in the head and neck area (94%), and the
mean age of the patients was 69.8 years. Margin involvements were seen in 11
patients (31.4%) and all of them underwent re-excision. There was only one local
recurrence. There was neither regional lymph node nor distant metastasis in this
series. The recurrence rate of basosquamous carcinoma is found as 4%, lower than
that of most other similar studies. Further pathologic studies are needed to
better classify basosquamous carcinoma and to increase consistency between the
results of studies. Surgical excision and regular follow-up are considered as the
treatment of choice.
PMID- 25139416
TI - Streptococcus oriloxodontae sp. nov., isolated from the oral cavities of
elephants.
AB - Two strains were isolated from oral cavity samples of healthy elephants. The
isolates were Gram-positive, catalase-negative, coccus-shaped organisms that were
tentatively identified as a streptococcal species based on the results of
biochemical tests. Comparative 16S rRNA gene sequence analysis suggested
classification of these organisms in the genus Streptococcus with Streptococcus
criceti ATCC 19642(T) and Streptococcus orisuis NUM 1001(T) as their closest
phylogenetic neighbours with 98.2 and 96.9% gene sequence similarity,
respectively. When multi-locus sequence analysis using four housekeeping genes,
groEL, rpoB, gyrB and sodA, was carried out, similarity of concatenated sequences
of the four housekeeping genes from the new isolates and Streptococcus mutans was
89.7%. DNA-DNA hybridization experiments suggested that the new isolates were
distinct from S. criceti and other species of the genus Streptococcus. On the
basis of genotypic and phenotypic differences, it is proposed that the novel
isolates are classified in the genus Streptococcus as representatives of
Streptococcus oriloxodontae sp. nov. The type strain of S. oriloxodontae is NUM
2101(T) ( =JCM 19285(T) =DSM 27377(T)).
PMID- 25139417
TI - Geobacter soli sp. nov., a dissimilatory Fe(III)-reducing bacterium isolated from
forest soil.
AB - A novel Fe(III)-reducing bacterium, designated GSS01(T), was isolated from a
forest soil sample using a liquid medium containing acetate and ferrihydrite as
electron donor and electron acceptor, respectively. Cells of strain GSS01(T) were
strictly anaerobic, Gram-stain-negative, motile, non-spore-forming and slightly
curved rod-shaped. Growth occurred at 16-40 degrees C and optimally at 30
degrees C. The DNA G+C content was 60.9 mol%. The major respiratory quinone was
MK-8. The major fatty acids were C(16:0), C(18:0) and
C(16:1)omega7c/C(16:1)omega6c. Strain GSS01(T) was able to grow with
ferrihydrite, Fe(III) citrate, Mn(IV), sulfur, nitrate or anthraquinone-2,6
disulfonate, but not with fumarate, as sole electron acceptor when acetate was
the sole electron donor. The isolate was able to utilize acetate, ethanol,
glucose, lactate, butyrate, pyruvate, benzoate, benzaldehyde, m-cresol and phenol
but not toluene, p-cresol, propionate, malate or succinate as sole electron donor
when ferrihydrite was the sole electron acceptor. Phylogenetic analyses based on
16S rRNA gene sequences revealed that strain GSS01(T) was most closely related to
Geobacter sulfurreducens PCA(T) (98.3% sequence similarity) and exhibited low
similarities (94.9-91.8%) to the type strains of other species of the genus
Geobacter. The DNA-DNA relatedness between strain GSS01(T) and G. sulfurreducens
PCA(T) was 41.4 +/- 1.1%. On the basis of phylogenetic analysis, phenotypic
characterization and physiological tests, strain GSS01(T) is believed to
represent a novel species of the genus Geobacter, and the name Geobacter soli sp.
nov. is proposed. The type strain is GSS01(T) ( =KCTC 4545(T) =MCCC 1K00269(T)).
PMID- 25139418
TI - Taxonomy and phylogeny of two species of the genus Deviata (Protista, Ciliophora)
from China, with description of a new soil form, Deviata parabacilliformis sp.
nov.
AB - The morphology and morphogenesis of a soil hypotrichous ciliate, Deviata
parabacilliformis sp. nov., isolated from northern China, were investigated. D.
parabacilliformis measures about 75-210 * 25-60 um in vivo, with an elongate and
flexible body. It possesses one right marginal row, two to four left marginal
rows and three dorsal kineties. The main morphogenetic features of D.
parabacilliformis are: (i) the oral primordium originates de novo; (ii) anlage IV
of the opisthe originates from parental frontoventral row V, anlage V originates
de novo, and anlage VI forms from frontoventral row VI; and (iii) anlage I of the
proter originates from the anterior portion of the parental paroral, anlage II
originates from the buccal cirrus, anlage III originates from the parabuccal
cirri, anlage IV originates from parental frontoventral row IV and anlage V forms
from the anterior of parental frontoventral row VI. The morphology of an edaphic
population of another species of the genus Deviata, Deviata bacilliformis (Gelei
1954) Eigner 1995, was also investigated. This work also provides the first
record of SSU rRNA gene sequences for species of the genus Deviata. Molecular
phylogenetic analysis suggests that Deviata is not monophyletic, and its position
is poorly resolved due to weak phylogenetic signal of the 18S marker in the
Stichotrichida.
PMID- 25139419
TI - Is the Sequential Laser Technique for Twin-to-Twin Transfusion Syndrome Truly
Superior to the Standard Selective Technique? A Meta-Analysis.
AB - BACKGROUND AND OBJECTIVE: To investigate the efficacy of sequential laser
coagulation in the treatment of twin-to-twin transfusion syndrome (TTTS). DATA
SOURCES: MEDLINE, EMBASE and the Cochrane Library were systematically searched
for comparative studies on the efficacy of sequential versus standard selective
laser coagulation for TTTS. The primary outcome measure in these studies was
survival of at least one twin, both twins and fetal demise. RESULTS: Three cohort
studies comparing the selective laser treatment technique (n = 120) versus the
sequential technique (n = 224) in 344 monochorionic twin pregnancies were
included. Mean survival of at least one twin was 88% in the selective group
versus 92% (p = 0.22) in the sequential group. Mean survival of both twins was
lower in the selective group (52%) than in the sequential group (75%) (p =
0.002). Donor fetal demise decreased from 34% in the selective to 10% in the
sequential group (p < 0.01), and recipient fetal demise decreased from 16 to 7%
(p = 0.02). CONCLUSION: Limited evidence suggests improved double neonatal
survival as well as decreased donor and recipient fetal demise with the use of
the sequential technique. However, these results are based on small non
randomized studies with evident forms of bias and methodological limitations. A
randomized controlled trial to assess the efficacy of sequential laser technique
is therefore required.
PMID- 25139420
TI - Neural processing of recollection, familiarity and priming at encoding: evidence
from a forced-choice recognition paradigm.
AB - The distinction between neural mechanisms of explicit and implicit expressions of
memory has been well studied at the retrieval stage, but less at encoding. In
addition, dissociations obtained in many studies are complicated by
methodological difficulties in obtaining process-pure measures of different types
of memory. In this experiment, we applied a subsequent memory paradigm and a two
stage forced-choice recognition test to classify study ERP data into four
categories: subsequent remembered (later retrieved accompanied by detailed
information), subsequent known (later retrieved accompanied by a feeling of
familiarity), subsequent primed (later retrieved without conscious awareness) and
subsequent forgotten (not retrieved). Differences in subsequent memory effects
(DM effects) were measured by comparing ERP waveform associated with later memory
based on recollection, familiarity or priming with ERP waveform for later
forgotten items. The recollection DM effect involved a robust sustained (onset at
300 ms) prefrontal positive-going DM effect which was right-lateralized, and a
later (onset at 800 ms) occipital negative-going DM effect. Familiarity involved
an earlier (300-400 ms) prefrontal positive-going DM effect and a later (500-600
ms) parietal positive-going DM effect. Priming involved a negative-going DM
effect which onset at 600 ms, mainly distributed over anterior brain sites. These
results revealed a sequence of components that represented cognitive processes
underlying the encoding of verbal information into episodic memory, and
separately supported later remembering, knowing and priming.
PMID- 25139421
TI - Adverse effects of antipsychotics on micro-vascular endothelial cells of the
human blood-brain barrier.
AB - Although the mechanisms of action of antipsychotics (APs) on neuronal function
are well understood, very little is known about their effects on cells of the
blood-brain barrier (BBB); one function of which is to limit the access of these
amphiphilic compounds to the central nervous system. To address this question we
have investigated the cytological and functional effects of four APs:
chlorpromazine (CLP), haloperidol (HAL), risperidone (RIS) and clozapine (CLZ),
at concentrations typical of high therapeutic dosage on a human brain
microvascular endothelial cell (HBMEC) model of the BBB. At ~10 uM all four APs
impaired the ability of HBMECs to reduce MTT which was followed by decreased
Trypan blue exclusion and increased Lactate dehydrogenase release. These effects
were associated with oxidative stress which was partly reversed by incubation in
10mM glutathione. At their EC50 concentrations for MTT reduction, all four APs
disrupted cellular ultrastructure and morphology. HAL, CPZ and CLZ increased
Caspase -3, -8 and -9 activity, chromatin condensation and fragmentation, data
indicative of apoptosis. These events were associated with decreased transcytosis
of Evans blue and increased transendothelial potential difference and electrical
resistance of this BBB model. These findings suggest that at high therapeutic
concentrations, CPZ and CLZ are likely to incur cytoxic effects and apoptosis of
BBB endothelia with an impairment of barrier functionality. Such events may
underlie the aetiology of neuroleptic associated cerebral oedema and neuroleptic
malignant syndrome.
PMID- 25139422
TI - Musical phrase boundaries, wrap-up and the closure positive shift.
AB - We investigated global integration (wrap-up) processes at the boundaries of
musical phrases by comparing the effects of well and non-well formed phrases on
event-related potentials time-locked to two boundary points: the onset and the
offset of the boundary pause. The Closure Positive Shift, which is elicited at
the boundary offset, was not modulated by the quality of phrase structure (well
vs. non-well formed). In contrast, the boundary onset potentials showed different
patterns for well and non-well formed phrases. Our results contribute to specify
the functional meaning of the Closure Positive Shift in music, shed light on the
large-scale structural integration of musical input, and raise new hypotheses
concerning shared resources between music and language.
PMID- 25139423
TI - Polyglutamine-expanded ataxin-3 impairs long-term depression in Purkinje neurons
of SCA3 transgenic mouse by inhibiting HAT and impairing histone acetylation.
AB - Our previous study using a transgenic mouse model of spinocerebellar ataxia type
3 (SCA3) reported that disease-causing ataxin-3-Q79 caused cerebellar malfunction
by inducing transcriptional downregulation. Long-term depression (LTD) of
parallel fiber-Purkinje neuron glutamatergic transmission is believed to be a
cellular mechanism for motor learning and motor coordination in the cerebellum.
Downregulated mRNA expression of calcineurin B, IP3-R1, myosin Va and PLC beta4,
which are required for the induction of cerebellar LTD, led to an impairment of
LTD induction in Purkinje neurons of SCA3 transgenic mouse. Our study suggested
that ataxin-3-Q79 caused hypoacetylation of cerebellar histone H3 or H4 by
inhibiting the activity of histone acetyltransferase (HAT) without affecting the
activity of histone deacetylase (HDAC). Consistent with the hypothesis that
hypoacetylated H3 or H4 histone associated with promoter regions of downregulated
genes is the molecular mechanism underlying ataxin-3-Q79-induced transcriptional
repression, chromatin immunoprecipitation-quantitative real-time PCR analysis
showed hypoacetylation of H3 or H4 histone associated with the proximal promoter
of downregulated calcineurin B, IP3-R1, myosin Va or PLC beta4 gene in the
cerebellum of SCA3 mouse. HDAC inhibitor sodium butyrate reversed ataxin-3-Q79
induced hypoacetylation of histone H3 or H4 associated with the proximal promoter
of calcineurin B, IP3-R1, myosin Va or PLC beta4 gene. Sodium butyrate also
prevented ataxin-3-Q79-induced impairment of LTD induction in Purkinje neurons of
SCA3 mice. Our results suggest that polyglutamine-expanded ataxin-3-Q79 impairs
HAT activity, leading to histone hypoacetylation, downregulated expression of
cerebellar genes required for LTD induction and impaired induction of cerebellar
LTD in the SCA3 transgenic mouse.
PMID- 25139424
TI - What's new in the literature: an update of new research since the original WHS
diabetic foot ulcer guidelines in 2006.
AB - The objective of the paper was to update the diabetic foot ulcer guidelines that
were previously published in 2006. We performed a key word search using MEDLINE
and Cochrane reviews for publication between January 2006 and January 2012.
Articles that fit the inclusion criteria were reviewed and the previous
guidelines were updated.
PMID- 25139425
TI - Trophic niche and habitat shifts of sympatric Gerreidae.
AB - The diet and mouth growth rates of three Gerreidae species (Eugerres brasilianus,
Eucinostomus melanopterus and Diapterus rhombeus) were assessed at different
ontogenetic phases (juveniles, sub-adults and adults) in order to detect
allometric growth, and whether they are related to habitat and seasonal changes
in the Goiana Estuary, north-east Brazil. The importance of each prey for each
ontogenetic phase was described using the index of relative importance. The three
species showed seasonal ontogenetic shifts in diet and allometric growth of mouth
morphology. They also had an exclusively zoobenthic diet, comprising mainly
Polychaeta, Copepoda, Ostracoda, Gastropoda and Bivalvia. Mouth development
showed a possible influence on diet changes for E. melanopterus. Significant
interactions (P < 0.01) were detected among seasons, areas and ontogenetic phases
for the most important prey for E. brasilianus and E. melanopterus. Diet overlaps
are evidence of intra and interspecific competition among gerreids for specific
prey. A conceptual model of the competition and seasonal diet shifts among
ontogenetic phases of gerreids is given. The sediment ingested due to the feeding
mechanisms of Gerreidae species could also partially explain the ingestion of
synthetic items observed for all ontogenetic phases, which indicates one of a
myriad effects of human activities (e.g. artisanal fishery) in this estuary.
PMID- 25139426
TI - Effect of cooked white rice with high beta-glucan barley on appetite and energy
intake in healthy Japanese subjects: a randomized controlled trial.
AB - White rice is a dominant grain-based food in Japan, but excess intake of polished
rice may cause obesity. Barley is a grain-based food, similar to white rice, but
it has the potential to control appetite and reduce energy intake. We
investigated the effect of cooked white rice with high beta-glucan barley on
appetite and energy intake. The study was conducted as a randomized crossover
design with twenty-one healthy Japanese women [mean +/- standard deviation body
mass index (BMI) 23.3 +/- 0.7 kg/m(2)]. Subjects consumed a breakfast of cooked
white rice with high beta-glucan barley (BAR) or white rice (WR), followed by an
ad libitum lunch and dinner. Energy intake was measured at the lunch and the
dinner using plate waste. Subjects' perception scores on hunger, fullness,
satiety, and prospective food consumption were assessed using a visual analogue
scale (VAS) before and after the breakfast, lunch and dinner. BAR significantly
reduced the VAS scores of hunger and prospective food consumption, and increased
fullness before lunch compared to WR (P = 0.032, 0.019 and 0.038, respectively).
Energy intake at lunch and the cumulative energy intake (lunch + dinner)
subsequent to BAR consumption were significantly lower than WR (P = 0.035 and
0.021, respectively). BAR was able to modulate appetite and reduce energy intake.
The combination of white rice with high beta-glucan barley could play a
beneficial role in preventing and treating obesity and other obesity-related
metabolic diseases.
PMID- 25139427
TI - Molecular cloning of two novel peroxidases and their response to salt stress and
salicylic acid in the living fossil Ginkgo biloba.
AB - BACKGROUND AND AIMS: Peroxidase isoenzymes play diverse roles in plant
physiology, such as lignification and defence against pathogens. The actions and
regulation of many peroxidases are not known with much accuracy. A number of
studies have reported direct involvement of peroxidase isoenzymes in the
oxidation of monolignols, which constitutes the last step in the lignin
biosynthesis pathway. However, most of the available data concern only
peroxidases and lignins from angiosperms. This study describes the molecular
cloning of two novel peroxidases from the 'living fossil' Ginkgo biloba and their
regulation by salt stress and salicylic acid. METHODS: Suspension cell cultures
were used to purify peroxidases and to obtain the cDNAs. Treatments with
salicylic acid and sodium chloride were performed and peroxidase activity and
gene expression were monitored. KEY RESULTS: A novel peroxidase was purified,
which preferentially used p-hydroxycinnamyl alcohols as substrates and was able
to form dehydrogenation polymers in vitro from coniferyl and sinapyl alcohols.
Two peroxidase full-length cDNAs, GbPrx09 and GbPrx10, were cloned. Both
peroxidases showed high similarity to other basic peroxidases with a putative
role in cell wall lignification. Both GbPrx09 and GbPrx10 were expressed in
leaves and stems of the plant. Sodium chloride enhanced the gene expression of
GbPrx09 but repressed GbPrx10, whereas salicylic acid strongly repressed both
GbPrx09 and GbPrx10. CONCLUSIONS: Taken together, the data suggest the
participation of GbPrx09 and GbPrx10 in the developmental lignification programme
of the cell wall. Both peroxidases possess the structural characteristics
necessary for sinapyl alcohol oxidation. Moreover, GbPrx09 is also involved in
lignification induced by salt stress, while salicylic acid-mediated lignification
is not a result of GbPrx09 and GbPrx10 enzymatic activity.
PMID- 25139428
TI - Floral structure of Emmotum (Icacinaceae sensu stricto or Emmotaceae), a
phylogenetically isolated genus of lamiids with a unique pseudotrimerous
gynoecium, bitegmic ovules and monosporangiate thecae.
AB - BACKGROUND AND AIMS: Icacinaceae sensu stricto consist of a group of early
branching lineages of lamiids whose relationships are not yet resolved and whose
detailed floral morphology is poorly known. The most bizarre flowers occur in
Emmotum: the gynoecium has three locules on one side and none on the other. It
has been interpreted as consisting of three fertile and two sterile carpels or of
one fertile carpel with two longitudinal septa and two sterile carpels. This
study focused primarily on the outer and inner morphology of the gynoecium to
resolve its disputed structure, and ovule structure was also studied. In
addition, the perianth and androecium were investigated. METHODS: Flowers and
floral buds of two Emmotum species, E. harleyi and E. nitens, were collected and
fixed in the field, and then studied by scanning electron microscopy. Microtome
section series were used to reconstruct their morphology. KEY RESULTS: The
gynoecium in Emmotum was confirmed as pentamerous, consisting of three fertile
and two sterile carpels. Each of the three locules behaves as the single locule
in other Icacinaceae, with the placenta of the two ovules being identical, which
shows that three fertile carpels are present. In addition, it was found that the
ovules are bitegmic, which is almost unique in lamiids, and that the stamens have
monosporangiate thecae, which also occurs in the closely related family
Oncothecaceae, but is not known from any other Icacinaceae sensu lato so far.
CONCLUSIONS: The flowers of Emmotum have unique characters at different
evolutionary levels: the pseudotrimerous gynoecium at angiosperm level, the
bitegmic ovules at lamiid level and the monosporangiate thecae at family or
family group level. However, in general, the floral morphology of Emmotum fits
well in Icacinaceae. More comparative research on flower structure is necessary
in Icacinaceae and other early branching lineages of lamiids to better understand
the initial evolution of this large lineage of asterids.
PMID- 25139430
TI - Ophthalmic imaging.
AB - INTRODUCTION OR BACKGROUND: The last two decades have seen a revolution in
ophthalmic imaging. In this review we present an overview of the breadth of
ophthalmic imaging modalities in use today and describe how the role of
ophthalmic imaging has changed from documenting abnormalities visible on clinical
examination to the detection of clinically silent abnormalities which can lead to
an earlier and more precise diagnosis. SOURCES OF DATA: This review is based on
published literature in the fields of ophthalmic imaging and with focus on most
commonly used imaging modalities. AREAS OF AGREEMENT: New imaging techniques
enable non-invasive evaluation of ocular structures at a resolution of a few
micrometres. This has led to a re-evaluation of diagnostic criteria for ocular
disease, which were previously defined by clinical findings without significant
reference to imaging. AREAS OF CONTROVERSY: Lack of formal training and clinical
guidelines regarding use of new imaging techniques in diagnosing and monitoring
various ocular conditions. Lack of large normative databases and
interchangeability issues between different commercial machines can hinder the
detection of disease progression. GROWING POINTS: Imaging devices are being
constantly refined with improved image capture and image analysis tools. AREAS
TIMELY FOR DEVELOPING RESEARCH: Clinical applications of new techniques and
devices have yet to be determined using systematic scientific research methods.
PMID- 25139431
TI - A multidisciplinary approach to determine factors associated with calf rearing
practices and calf mortality in dairy herds.
AB - In the Netherlands, an increase in ear-tagged calf mortality (3 days to 1 year of
age) in dairy farms was observed. The aim was to determine why calf mortality
increased and how to reduce calf mortality in herds with structural high rates. A
multi-disciplinary approach was chosen to study this phenomenon. First analysis
of census data revealed that the majority of the calves died in the first month
of life. In addition, a panel of 236 farmers indicated that the increase in calf
mortality might be related to priority, time management and the mind-set of
farmers. For that reason a questionnaire was carried out to detect risk factors
for mortality among young calves (<1 month) in 100 dairy farms with increased
calf mortality compared to 100 dairy farms with stable and below average calf
mortality. The results showed that, besides management factors such as IBR and
BVDV control, and purchase of cattle, also the answers to statements giving an
indication on the farmers' mind-set, were associated with calf mortality.
Therefore, a qualitative sociological study on the farmers' identity was
conducted by performing in-depth interviews among 30 farmers with structurally
high calf mortality rates. Afterwards, the results were communicated with a
veterinary advisor who visited the farmers and gave tailored advice. Most of the
interviewed farmers believed to have sufficient knowledge and skills regarding
calf rearing. The farmers did not share their calf rearing problems with
colleagues and advisors but they mentioned to be open to receive advice if not
communicated in a reproaching or pedantic way. The sociologist distinguished
three different phases of awareness concerning calf mortality among the farmers:
(1) farmers who were only partly, or not at all, aware of high calf mortality;
(2) farmers who felt powerless because of their inability to find a solution to
their problems; and (3) farmers who knew they can be inaccurate when it comes to
rearing calves, but were reluctant to change this. With the background
information of the farmers' identity it was easier for the veterinary advisor to
provide tailored advice resulting in a higher probability of following up. A
first evaluation in which calf mortality rates in the six months after providing
the advice were monitored, indicated that the advice resulted in reduced
mortality. The combination of census data, epidemiological and qualitative
sociological research revealed that advisors should be aware of the attitude and
mind-set of the farmer and adapt their approach and advice accordingly.
PMID- 25139429
TI - Back to the future with the AGP-Ca2+ flux capacitor.
AB - BACKGROUND: Arabinogalactan proteins (AGPs) are ubiquitous in green plants. AGPs
comprise a widely varied group of hydroxyproline (Hyp)-rich cell surface
glycoproteins (HRGPs). However, the more narrowly defined classical AGPs
massively predominate and cover the plasma membrane. Extensive glycosylation by
pendant polysaccharides O-linked to numerous Hyp residues like beads of a
necklace creates a unique ionic compartment essential to a wide range of
physiological processes including germination, cell extension and fertilization.
The vital clue to a precise molecular function remained elusive until the recent
isolation of small Hyp-arabinogalactan polysaccharide subunits; their structural
elucidation by nuclear magentic resonance imaging, molecular simulations and
direct experiment identified a 15-residue consensus subunit as a beta-1,3-linked
galactose trisaccharide with two short branched sidechains each with a single
glucuronic acid residue that binds Ca(2+) when paired with its adjacent
sidechain. SCOPE: AGPs bind Ca(2+) (Kd ~ 6 MUm) at the plasma membrane (PM) at pH
~5.5 but release it when auxin-dependent PM H(+)-ATPase generates a low
periplasmic pH that dissociates AGP-Ca(2+) carboxylates (pka ~3); the
consequential large increase in free Ca(2+) drives entry into the cytosol via
Ca(2+) channels that may be voltage gated. AGPs are thus arguably the primary
source of cytosolic oscillatory Ca(2+) waves. This differs markedly from animals,
in which cytosolic Ca(2+) originates mostly from internal stores such as the
sarcoplasmic reticulum. In contrast, we propose that external dynamic Ca(2+)
storage by a periplasmic AGP capacitor co-ordinates plant growth, typically
involving exocytosis of AGPs and recycled Ca(2+), hence an AGP-Ca(2+) oscillator.
CONCLUSIONS: The novel concept of dynamic Ca(2+) recycling by an AGP-Ca(2+)
oscillator solves the long-standing problem of a molecular-level function for
classical AGPs and thus integrates three fields: AGPs, Ca(2+) signalling and
auxin. This accounts for the involvement of AGPs in plant morphogenesis,
including tropic and nastic movements.
PMID- 25139432
TI - A novel method to identify herds with an increased probability of disease
introduction due to animal trade.
AB - In the design of surveillance, there is often a desire to target high risk herds.
Such risk-based approaches result in better allocation of resources and improve
the performance of surveillance activities. For many contagious animal diseases,
movement of live animals is a main route of transmission, and because of this,
herds that purchase many live animals or have a large contact network due to
trade can be seen as a high risk stratum of the population. This paper presents a
new method to assess herd disease risk in animal movement networks. It is an
improvement to current network measures that takes direction, temporal order, and
also movement size and probability of disease into account. In the study, the
method was used to calculate a probability of disease ratio (PDR) of herds in
simulated datasets, and of real herds based on animal movement data from dairy
herds included in a bulk milk survey for Coxiella burnetii. Known differences in
probability of disease are easily incorporated in the calculations and the PDR
was calculated while accounting for regional differences in probability of
disease, and also by applying equal probability of disease throughout the
population. Each herd's increased probability of disease due to purchase of
animals was compared to both the average herd and herds within the same risk
stratum. The results show that the PDR is able to capture the different
circumstances related to disease prevalence and animal trade contact patterns.
Comparison of results based on inclusion or exclusion of differences in risk also
highlights how ignoring such differences can influence the ability to correctly
identify high risk herds. The method shows a potential to be useful for risk
based surveillance, in the classification of herds in control programmes or to
represent influential contacts in risk factor studies.
PMID- 25139433
TI - I want it all and I want it now: Delay of gratification in preschool children.
AB - On the delay-of-gratification choice paradigm, 4-year-olds typically choose the
larger, delayed reward, exhibiting delay of gratification, whereas 3-year-olds
typically choose the small, immediate reward. Despite this highly replicated
finding, the cognitive mechanism(s) underlying 3-year-olds' failure on the choice
paradigm remain unclear. Recently, several researchers have proposed the
involvement of the "hot" affective system and the "cool" cognitive system in pre
schoolers' performance on the choice paradigm. Using this "hot" and "cool"
systems framework, we tested 112 3- and 4-year-olds on a modified choice paradigm
that was designed to help young children better utilize their "cool" system,
allowing them to make more mindful and future-oriented decisions. In the modified
paradigm, 3-year-olds made choices consistent with those of 4-year-olds,
exhibiting delay of gratification. These findings have important implications for
previous theoretical accounts of 3-year-old children's failure to delay
gratification. Additionally, they highlight the critical role that the method
plays in young children's performance on cognitive paradigms.
PMID- 25139434
TI - Population structure and genetic analysis of narrow-clawed crayfish (Astacus
leptodactylus) populations in Turkey.
AB - The genetic differentiation among Turkish populations of the narrow-clawed
crayfish was investigated using a partial sequence of cytochrome oxidase subunit
I gene (585 bp) of 183 specimens from 17 different crayfish populations. Median
joining network and all phylogenetic analyses disclosed a strong haplotype
structure with three prominent clades diverged by a range between 20 and 50
mutations and substantial inter-group pairwise sequence divergence (5.19-6.95 %),
suggesting the presence of three distinct clades within the Anatolian populations
of Astacus leptodactylus. The divergence times among the three clades of Turkish
A. leptodactylus are estimated to be 4.96-3.70 Mya using a molecular clock of 1.4
% sequence divergence per million years, pointing to a lower Pliocene separation.
The high level of genetic variability (H d = 95.8 %, pi = 4.17 %) and numerous
private haplotypes suggest the presence of refugial populations in Anatolia
unaffected by Pleistocene habitat restrictions. The pattern of genetic variation
among Turkish A. leptodactylus populations, therefore, suggests that the
unrevealed intraspecific genetic structure is independent of geographic tendency
and congruent with the previously reported geographic distribution and number of
subspecies (A. l. leptodactylus and A. l. salinus) of A. leptodactylus.
PMID- 25139435
TI - Mesenchymal stromal cells: the magic Band-Aid?
PMID- 25139437
TI - [PROMIS((r)): A platform to evaluate health status and the results of
interventions].
PMID- 25139436
TI - Enterovirus 71-induced autophagy increases viral replication and pathogenesis in
a suckling mouse model.
AB - BACKGROUND: We previously reported that Enterovirus 71 (EV71) infection activates
autophagy, which promotes viral replication both in vitro and in vivo. In the
present study we further investigated whether EV71 infection of neuronal SK-N-SH
cells induces an autophagic flux. Furthermore, the effects of autophagy on EV71
related pathogenesis and viral load were evaluated after intracranial inoculation
of mouse-adapted EV71 (MP4 strain) into 6-day-old ICR suckling mice. RESULTS: We
demonstrated that in EV71-infected SK-N-SH cells, EV71 structural protein VP1 and
nonstructural protein 2C co-localized with LC3 and mannose-6-phosphate receptor
(MPR, endosome marker) proteins by immunofluorescence staining, indicating
amphisome formation. Together with amphisome formation, EV71 induced an
autophagic flux, which could be blocked by NH4Cl (inhibitor of acidification) and
vinblastine (inhibitor of fusion), as demonstrated by Western blotting. Suckling
mice intracranially inoculated with EV71 showed EV71 VP1 protein expression
(representing EV71 infection) in the cerebellum, medulla, and pons by
immunohistochemical staining. Accompanied with these infected brain tissues,
increased expression of LC3-II protein as well as formation of LC3 aggregates,
autophagosomes and amphisomes were detected. Amphisome formation, which was
confirmed by colocalization of EV71-VP1 protein or LC3 puncta and the endosome
marker protein MPR. Thus, EV71-infected suckling mice (similar to EV71-infected
SK-N-SH cells) also show an autophagic flux. The physiopathological parameters of
EV71-MP4 infected mice, including body weight loss, disease symptoms, and
mortality were increased compared to those of the uninfected mice. We further
blocked EV71-induced autophagy with the inhibitor 3-methyladenine (3-MA), which
attenuated the disease symptoms and decreased the viral load in the brain tissues
of the infected mice. CONCLUSIONS: In this study, we reveal that EV71 infection
of suckling mice induces an amphisome formation accompanied with the autophagic
flux in the brain tissues. Autophagy induced by EV71 promotes viral replication
and EV71-related pathogenesis.
PMID- 25139438
TI - Total synthesis and biological studies of cryptocin and derivatives of equisetin
and fusarisetin A.
AB - Total synthesis of cryptocin, a fungus metabolite, was achieved based on the
biosynthetic hypothesis. A variety of derivatives of cryptocin, equisetin and
fusarisetin A were prepared, wherein the racemization of C-3 and
diastereoselectivity of C-5 were investigated. We further examined their
inhibitory effects on breast cancer cell survival and metastasis, and summarized
the structure-activity relationship.
PMID- 25139440
TI - Novel paracrine modulation of Notch-DLL4 signaling by fibulin-3 promotes
angiogenesis in high-grade gliomas.
AB - High-grade gliomas are characterized by exuberant vascularization, diffuse
invasion, and significant chemoresistance, resulting in a recurrent phenotype
that makes them impossible to eradicate in the long term. Targeting protumoral
signals in the glioma microenvironment could have significant impact against
tumor cells and the supporting niche that facilitates their growth. Fibulin-3 is
a protein secreted by glioma cells, but absent in normal brain, that promotes
tumor invasion and survival. We show here that fibulin-3 is a paracrine activator
of Notch signaling in endothelial cells and promotes glioma angiogenesis. Fibulin
3 overexpression increased tumor VEGF levels, microvascular density, and vessel
permeability, whereas fibulin-3 knockdown reduced vessel density in xenograft
models of glioma. Fibulin-3 localization in human glioblastomas showed dense
fiber-like condensations around tumor blood vessels, which were absent in normal
brain, suggesting a remarkable association of this protein with tumor
endothelium. At the cellular level, fibulin-3 enhanced endothelial cell motility
and association to glioma cells, reduced endothelial cell sprouting, and
increased formation of endothelial tubules in a VEGF-independent and Notch
dependent manner. Fibulin-3 increased ADAM10/17 activity in endothelial cells by
inhibiting the metalloprotease inhibitor TIMP3; this resulted in increased Notch
cleavage and increased expression of DLL4 independently of VEGF signaling.
Inhibition of ADAM10/17 or knockdown of DLL4 reduced the proangiogenic effects of
fibulin-3 in culture. Taken together, these results reveal a novel, proangiogenic
role of fibulin-3 in gliomas, highlighting the relevance of this protein as an
important molecular target in the tumor microenvironment.
PMID- 25139441
TI - Radiation-induced secondary malignancy in prostate cancer: a systematic review
and meta-analysis.
AB - OBJECTIVE: To investigate the risk of radiation-induced secondary malignancy in
patients with prostate cancer. METHODS: We identified 690 references from PubMed,
Embase and the Cochrane Library before August 1, 2012, that reported secondary
malignancy in patients with prostate cancer after receiving radiation therapy
(RT), and finally four studies were included. We calculated summary estimates
using random-effects meta-analysis. RESULTS: The overall standardized incidence
ratio (SIR) of secondary malignancy in patients with prostate cancer receiving RT
to the general population was 1.14 (95% CI 1.04-1.32). In the subgroup analysis,
no increment in radiation-induced secondary malignancy risk was detected. In
terms of SIR with different follow-up intervals, there was no difference in SIR
(>6 months; <5 years) (SIR = 1.19, 95% CI 0.75-1.89) and SIR (>5 years; <10
years) (SIR = 1.39, 95% CI 0.87-2.23). When the follow-up extended to >10 years,
a significantly increased secondary malignancy risk was observed (SIR = 1.45, 95%
CI 1.23-1.72). There is no significantly increased secondary malignancy risk in
patients receiving no RT. CONCLUSION: RT is associated with increased secondary
malignancy in patients with prostate cancer; this effect only become conspicuous
more than 10 years after treatment.
PMID- 25139442
TI - Boron-double-ring sheet, fullerene, and nanotubes: potential hydrogen storage
materials.
AB - Similar to carbon-based graphene, fullerenes and carbon nanotubes, boron atoms
can form sheets, fullerenes, and nanotubes. Here we investigate several of these
novel boron structures all based on the boron double ring within the framework of
density functional theory. The boron sheet is found to be metallic and flat in
its ground state. The spherical boron cage containing 180 atoms is also stable
and has I symmetry. Stable nanotubes are obtained by rolling up the boron sheet,
and all are metallic. The hydrogen storage capacity of boron nanostructures is
also explored, and it is found that Li-decorated boron sheets and nanotubes are
potential candidates for hydrogen storage. For Li-decorated boron sheets, each Li
atom can adsorb a maximum of 4 H2 molecules with g(d) =7.892 wt %. The hydrogen
gravimetric density increases to g(d) =12.309 wt % for the Li-decorated (0,6)
boron nanotube.
PMID- 25139443
TI - Adult newborn neurons are involved in learning acquisition and long-term memory
formation: the distinct demands on temporal neurogenesis of different cognitive
tasks.
AB - There is evidence that adult hippocampal neurogenesis influences hippocampal
function, although the role these neurons fulfill in learning and consolidation
processes remains unclear. Using a novel fast X-ray ablation protocol to deplete
neurogenic cells, we demonstrate that immature adult hippocampal neurons are
required for hippocampal learning and long-term memory formation. Moreover, we
found that long-term memory formation in the object recognition and passive
avoidance tests, two paradigms that involve circuits with distinct emotional
components, had different temporal demands on hippocampal neurogenesis. These
results reveal new and unexpected aspects of neurogenesis in cognitive processes.
PMID- 25139444
TI - Sudden arrhythmic death syndrome: diagnostic yield of comprehensive clinical
evaluation of pediatric first-degree relatives.
AB - AIMS: Sudden arrhythmic death syndrome (SADS) is most often caused by heritable
cardiac diseases. Studies in adults have identified evidence of inherited
cardiovascular diseases in up to 53% of families, but data on the prevalence of
familial disease in children are scarce. The aim of this study was to evaluate
the yield of clinical screening in pediatric first-degree relatives of victims of
SADS using a systematic and comprehensive protocol. METHODS: Patients referred
for family screening after sudden cardiac death (SCD) of a family member were,
retrospectively, enrolled into the study. Systematic evaluation of the children
included clinical examination, family history, electrocardiogram (ECG),
echocardiogram, 24-hour tape, and signal-averaged ECG. Older patients also
underwent exercise testing, cardiac magnetic resonance imaging, and ajmaline
provocation testing. RESULTS: A total of 90 children from 52 consecutive families
were included in the study. An inherited cardiac disease was identified in seven
first-degree children from seven (13.5%) families (five children were diagnosed
with Brugada syndrome, one with long QT syndrome, and one with catecholaminergic
polymorphic ventricular tachycardia). Two further children had late potentials on
signal-averaged ECGs with no other abnormalities. CONCLUSIONS: These data show a
high prevalence of inherited heart disease in pediatric first-degree relatives of
SADS victims. The results highlight the importance of a systematic, comprehensive
approach and ongoing screening of pediatric family members.
PMID- 25139445
TI - Reconfirmation of the anatomy of the left triangular ligament and the appendix
fibrosa hepatis in human livers, and its implication in abdominal surgery.
AB - BACKGROUND: The aim of the present study was to clarify the anatomy between the
left triangular ligament (LTL) and the appendix fibrosa hepatis (AFH) in order
not to sever the AFH when dissecting the LTL. METHODS: Totals of 43 and 27
cadaveric livers were examined macroscopically and histologically, respectively.
RESULTS: The LTL attached itself to the diaphragmatic surface of the AFH through
almost all lengths of the AFH. This might be the reason why AFH is so often
dissected together with the LTL. There were two types of relation between the LTL
and the AFH; in one type, the starting point of the LTL existed on the left liver
and in the other type, it was on the AFH. Twenty-five of 27 AFH included remnants
of the bile duct and 12 of 25 AFH had comparatively large bile ducts, which was
unexceptionally accompanied by the well-developed peribiliary vascular plexus.
AFH showed a variety of shapes, such as rectangular (6/43), long triangular
(4/43), short triangular (7/43), triangular plus cordlike (11/43), cordlike
(12/43) and bifurcated (3/43) types. CONCLUSIONS: As AFH sometimes includes
relatively large bile ducts, it is recommended for surgeons to sever the AFH not
just simply by electrocautery but by ligating its stump securely.
PMID- 25139446
TI - [Everyday competencies and learning processes in old age. Results and
perspectives of the PIAAC extension study "Competencies in later life"].
AB - This article deals with the study "Competencies in later life" (CiLL), a parallel
study to the German program for the international assessment of adult
competencies (PIAAC) survey which assesses the level and distribution of skills
of the adult population in a representative study. Assuming the growing
importance of learning and education in a society challenged by demographic
changes, the first section of the paper outlines the qualitative research of
learning activities of focus groups in the daily life of elderly people. The
second section of the paper presents the survey design and exemplary findings of
the quantitative CiLL study. Initial results show that basic skills of the
elderly are highly influenced by personal and sociodemographic variables,
particularly by educational background. The data available indicate that the
participation of the elderly in adult education and the options available for
competence development have to be increased.
PMID- 25139447
TI - Electroactive bacteria--molecular mechanisms and genetic tools.
AB - In nature, different bacteria have evolved strategies to transfer electrons far
beyond the cell surface. This electron transfer enables the use of these bacteria
in bioelectrochemical systems (BES), such as microbial fuel cells (MFCs) and
microbial electrosynthesis (MES). The main feature of electroactive bacteria
(EAB) in these applications is the ability to transfer electrons from the
microbial cell to an electrode or vice versa instead of the natural redox
partner. In general, the application of electroactive organisms in BES offers the
opportunity to develop efficient and sustainable processes for the production of
energy as well as bulk and fine chemicals, respectively. This review describes
and compares key microbiological features of different EAB. Furthermore, it
focuses on achievements and future prospects of genetic manipulation for
efficient strain development.
PMID- 25139448
TI - CO2 /HCO3- perturbations of simulated large scale gradients in a scale-down
device cause fast transcriptional responses in Corynebacterium glutamicum.
AB - The exploration of scale-down models to imitate the influence of large scale
bioreactor inhomogeneities on cellular metabolism is a topic with increasing
relevance. While gradients of substrates, pH, or dissolved oxygen are often
investigated, oscillating CO2/HCO3 (-) levels, a typical scenario in large
industrial bioreactors, is rarely addressed. Hereby, we investigate the metabolic
and transcriptional response in Corynebacterium glutamicum wild type as well as
the impact on L-lysine production in a model strain exposed to pCO2 gradients of
(75-315) mbar. A three-compartment cascade bioreactor system was developed and
characterized that offers high flexibility for installing gradients and residence
times to mimic industrial-relevant conditions and provides the potential of
accurate carbon balancing. The phenomenological analysis of cascade fermentations
imposed to the pCO2 gradients at industry-relevant residence times of about 3.6
min did not significantly impair the process performance, with growth and product
formation being similar to control conditions. However, transcriptional analysis
disclosed up to 66 differentially expressed genes already after 3.6 min under
stimulus exposure, with the overall change in gene expression directly
correlateable to the pCO2 gradient intensity and the residence time of the cells.
PMID- 25139449
TI - Revised scheme for the mechanism of photoinhibition and its application to
enhance the abiotic stress tolerance of the photosynthetic machinery.
AB - When photosynthetic organisms are exposed to abiotic stress, their photosynthetic
activity is significantly depressed. In particular, photosystem II (PSII) in the
photosynthetic machinery is readily inactivated under strong light and this
phenomenon is referred to as photoinhibition of PSII. Other types of abiotic
stress act synergistically with light stress to accelerate photoinhibition.
Recent studies of photoinhibition have revealed that light stress damages PSII
directly, whereas other abiotic stresses act exclusively to inhibit the repair of
PSII after light-induced damage (photodamage). Such inhibition of repair is
associated with suppression, by reactive oxygen species (ROS), of the synthesis
of proteins de novo and, in particular, of the D1 protein, and also with the
reduced efficiency of repair under stress conditions. Gene-technological
improvements in the tolerance of photosynthetic organisms to various abiotic
stresses have been achieved via protection of the repair system from ROS and,
also, by enhancing the efficiency of repair via facilitation of the turnover of
the D1 protein in PSII. In this review, we summarize the current status of
research on photoinhibition as it relates to the effects of abiotic stress and we
discuss successful strategies that enhance the activity of the repair machinery.
In addition, we propose several potential methods for activating the repair
system by gene-technological methods.
PMID- 25139450
TI - The dissection profile and mechanism of tissue-selective dissection of the piezo
actuator-driven pulsed water jet as a surgical instrument: laboratory
investigation using Swine liver.
AB - BACKGROUND/PURPOSE: The water jet technique dissects tissue while sparing cord
like structures such as blood vessels. The mechanism of such tissue-selective
dissection has been unknown. The novel piezo actuator-driven pulsed water jet
(ADPJ) system can achieve dissection with remarkably reduced water consumption
compared to the conventional water jet; however, the system's characteristics and
dissection capabilities on any organ have not been clarified. The purposes of
this study were to characterize the physical properties of the novel ADPJ system,
evaluate the dissection ability in swine organs, and reveal the mechanism of
tissue-selective dissection. METHODS: The pulsed water jet system comprised a
pump chamber driven by a piezo actuator, a stainless steel tube, and a nozzle.
The peak pressure of the pulsed water jet was measured through a sensing hole
using a pressure sensor. The pulsed water jet technique was applied on swine
liver in order to dissect tissue on a moving table using one-way linear ejection
at a constant speed. The dissection depth was measured with light microscopy and
evaluated histologically. The physical properties of swine liver were evaluated
by breaking strength tests using tabletop universal testing instruments. The
liver parenchyma was also cut with three currently available surgical devices to
compare the histological findings. RESULTS: The peak pressure of the pulsed water
jet positively correlated with the input voltage (R(2) = 0.9982, p < 0.0001), and
this was reflected in the dissection depth. The dissection depth negatively
correlated with the breaking strength of the liver parenchyma (R(2) = 0.6694, p <
0.0001). The average breaking strengths of the liver parenchyma, hepatic veins,
and Glisson's sheaths were 1.41 +/- 0.45, 8.66 +/- 1.70, and 29.6 +/- 11.0 MPa,
respectively. The breaking strength of the liver parenchyma was significantly
lower than that of the hepatic veins and Glisson's sheaths. Histological staining
confirmed that the liver parenchyma was selectively dissected, preserving the
hepatic veins and Glisson's sheaths in contrast to what is commonly observed with
electrocautery or ultrasonic instruments. CONCLUSIONS: The dissection depth of
liver tissue is well controlled by input voltage and is influenced by the moving
velocity and the physical properties of the organ. We showed that the device can
be used to assure liver resection with tissue selectivity due to tissue-specific
physical properties. Although this study uses an excised organ, further in vivo
studies are necessary. The present work demonstrates that this device may
function as an alternative tool for surgery due to its good controllability of
the dissection depth and ability of tissue selectivity.
PMID- 25139451
TI - The use of elemental mass spectrometry in phosphoproteomic applications.
AB - Reversible phosphorylation is one of the most important post-translational
modifications in mammalian cells. Because this molecular switch is an important
mechanism that diversifies and regulates proteins in cellular processes,
knowledge about the extent and quantity of phosphorylation is very important to
understand the complex cellular interplay. Although phosphoproteomics strategies
are applied worldwide, they mainly include only molecular mass spectrometry (like
MALDI or ESI)-based experiments. Although identification and relative
quantification of phosphopeptides is straightforward with these techniques,
absolute quantification is more complex and usually requires for specific
isotopically phosphopeptide standards. However, the use of elemental mass
spectrometry, and in particular inductively coupled plasma mass spectrometry (ICP
MS), in phosphoproteomics-based experiments, allow one to absolutely quantify
phosphopeptides. Here, these phosphoproteomic applications with ICP-MS as
elemental detector are reviewed. Pioneering work and recent developments in the
field are both described. Additionally, the advantage of the parallel use of
molecular and elemental mass spectrometry is stressed.
PMID- 25139452
TI - Socioecological factors in sexual decision making among urban girls and young
women.
AB - OBJECTIVES: To examine how girls and young women living in disadvantaged urban
neighborhoods make decisions relating to sexual debut and HIV prevention. DESIGN:
Thirty semistructured in-depth interviews. We used a socioecological approach to
investigate the role of neighborhood and social context on sexual decision
making. SETTING: Community-based organizations and on-campus interview sites.
PARTICIPANTS: African American and Latina girls and young women age 13 to 24
living in disadvantaged neighborhoods. METHODS: We examine their attitudes and
beliefs about sex, first opportunities for sexual intercourse, prevention
behaviors, and neighborhood environments. RESULTS: Lack of neighborhood safety
and safe socialization places led youth to spend significant amounts of time
indoors, often without adult supervision. CONCLUSION: The findings provide
insight into the socioecological context in which girls are situated as they
navigate sexual decision making. Unsupervised, cloistered time coupled with peer
norms to engage in sexual behavior may contribute to increased risky sexual
behavior among some youth. Prevention efforts should consider neighborhood
context and incorporate structural and community-level interventions to create
social environments that support healthy sexual decision making.
PMID- 25139453
TI - Can renal ultrasonography predict early success after pyeloplasty in children? A
prospective study.
AB - OBJECTIVE: To study the predictive value of 6 ultrasonographic (USG) parameters
for early detection of children at risk of recurrent obstruction. PATIENTS AND
METHODS: A prospective nonrandomized study included all patients who underwent
pyeloplasty between 2010 and 2012. All of the patients had completed at least 6
months of follow-up and preoperative and postoperative USG imaging data were
available. The primary outcome was the correlation between USG and diuretic
scintigraphic parameters. The secondary outcome was the predictive ability of the
pelvicalyceal system parameters, measured by USG, of parenchymal growth after
surgery. RESULTS: Sixty-eight patients were evaluated. The mean age was 3.6 years
(range 0.1-12). The mean (+/- standard deviation) differential renal function
improved from 37.4 +/- 11 ml/min to 37.7 +/- 14 ml/min, which was a difference of
no statistical significance. On the other hand, the mean (+/- SD) half-time
(T1/2) significantly improved. After constructing a linear regression model of
the 4 USG parameters and the parenchymal growth, the model explained 57.2% of the
variance in parenchymal growth after pyeloplasty. The calyx-to-parenchyma ratio
change was the largest unique contribution for explaining the variance in
parenchymal growth, followed by anteroposterior diameter and calyceal dilatation.
CONCLUSION: We proved that calyx-to-parenchyma ratio, anteroposterior diameter
and calyceal dilatation are independent predictors of early success after
pyeloplasty.
PMID- 25139454
TI - Antibiotic dispensation by Lebanese pharmacists: a comparison of higher and lower
socio-economic levels.
AB - INTRODUCTION: Indiscriminate use of antibiotics contributes to a global spread of
antimicrobial resistance. Previous studies showed an excessive consumption of
antibiotics purchased without medical prescription from community pharmacies,
mainly in developing countries. There is a shortage of studies revealing the role
of community pharmacists in the overuse of antibiotics. Our objective is to study
the dispensing policy of non-medical prescription antibiotics in community
pharmacies, assessing the possible influence of the socio-economic level of the
area over this practice. METHODS: A cross-sectional study was conducted between
February and May 2011 among 100 pharmacists working in Beirut's pharmacies and
its suburbs. Pharmacies were divided into 2 groups according to the socio
economic level of the population living in the pharmacy area. A self-administered
questionnaire was filled by pharmacists. RESULTS: Over-the-counter antibiotic
availability existed in both higher and lower socio-economic areas: on the whole,
32% of antibiotics were dispensed without medical prescription, with higher
frequency in lower socio-economic areas (p=0.003). Dispensing injectable
antibiotics without medical prescription was significantly higher in lower socio
economic areas (p=0.021), as well as dispensing an association of 2 antibiotics
without medical prescription (p=0.001). Pharmacists working in lower socio
economic areas recommended more frequent antibiotics to children and the elderly
(p<0.001 and p=0.004, respectively). CONCLUSION: Dispensing antibiotics without
medical prescription in Beirut community pharmacies is a common practice,
particularly in lower socioeconomic areas. This public health problem should be
addressed at the social, educational, and legislative levels.
PMID- 25139455
TI - Evidence of topological surface state in three-dimensional Dirac semimetal
Cd3As2.
AB - The three-dimensional topological semimetals represent a new quantum state of
matter. Distinct from the surface state in the topological insulators that
exhibits linear dispersion in two-dimensional momentum plane, the three
dimensional semimetals host bulk band dispersions linearly along all directions.
In addition to the gapless points in the bulk, the three-dimensional Weyl/Dirac
semimetals are also characterized by "topologically protected" surface state with
Fermi arcs on their surface. While Cd3As2 is proposed to be a viable candidate of
a Dirac semimetal, more investigations are necessary to pin down its nature. In
particular, the topological surface state, the hallmark of the three-dimensional
semimetal, has not been observed in Cd3As2. Here we report the electronic
structure of Cd3As2 investigated by angle-resolved photoemission measurements on
the (112) crystal surface and detailed band structure calculations. The measured
Fermi surface and band structure show a good agreement with the band structure
calculations with two bulk Dirac-like bands approaching the Fermi level and
forming Dirac points near the Brillouin zone center. Moreover, the topological
surface state with a linear dispersion approaching the Fermi level is identified
for the first time. These results provide experimental indications on the nature
of topologically non-trivial three-dimensional Dirac cones in Cd3As2.
PMID- 25139456
TI - Prognostic value of midregional pro-A-type natriuretic peptide and N-terminal pro
B-type natriuretic peptide in patients with stable coronary heart disease
followed over 8 years.
AB - BACKGROUND: Pathophysiological studies suggest that A-type natriuretic peptides
(ANPs) might provide valuable information beyond B-type natriuretic peptides
(BNPs) about cardiac dysfunction in patients with coronary heart disease (CHD).
We aimed to assess the predictive value of midregional pro-A-type natriuretic
peptide (MR-proANP) for recurrent cardiovascular disease (CVD) events in stable
CHD patients for whom information on N-terminal proBNP (NT-proBNP) was already
available. METHODS: Plasma concentrations of MR-proANP and NT-proBNP were
measured at baseline in a cohort of 1048 patients aged 30-70 years with CHD who
were participating in an in-hospital rehabilitation program. Main outcome
measures were cardiovascular mortality, nonfatal myocardial infarction, and
nonfatal stroke. RESULTS: During a median follow-up of 8.1 years, 150 patients
(incidence 21.1 per 1000 patient-years) experienced a secondary CVD event. MR
proANP was associated with a hazard ratio (HR) of 1.89 (95% CI, 1.01-3.57) when
the top quartile was compared to the bottom quartile in the fully adjusted model
(P for trend = 0.011). For NT-proBNP the respective HR was 2.22 (95% CI, 1.19
4.14) with a P for trend = 0.001. Finally, MR-proANP improved various model
performance measures, including c-statistics and reclassification metrics, but
without being superior to NT-proBNP. CONCLUSIONS: Although we found an
independent association of MR-proANP as well as NT-proBNP when used as single
markers with recurrent CVD events after adjustment for established risk factors,
the results of a simultaneous assessment of both markers indicated that MR-proANP
fails to provide additional prognostic information to NT-proBNP in the population
studied.
PMID- 25139457
TI - Integrative bioinformatics analysis reveals new prognostic biomarkers of clear
cell renal cell carcinoma.
AB - BACKGROUND: The outcome of clear cell renal cell carcinoma (ccRCC) is still
unpredictable. Even with new targeted therapies, the average progression-free
survival is dismal. Markers for early detection and progression could improve
disease outcome. METHODS: To identify efficient and hitherto unrecognized
pathogenic factors of the disease, we performed a uniquely comprehensive pathway
analysis and built a gene interaction network based on large publicly available
data sets assembled from 28 publications, comprising a 3-prong approach with high
throughput mRNA, microRNA, and protein expression profiles of 593 ccRCC and 389
normal kidney samples. We validated our results on 2 different data sets of 882
ccRCC and 152 normal tissues. Functional analyses were done by proliferation,
migration, and invasion assays following siRNA (small interfering RNA) knockdown.
RESULTS: After integration of multilevel data, we identified aryl-hydrocarbon
receptor (AHR), grainyhead-like-2 (GRHL2), and KIAA0101 as new pathogenic
factors. GRHL2 expression was associated with higher chances for disease relapse
and retained prognostic utility after controlling for grade and stage [hazard
ratio (HR), 3.47, P = 0.012]. Patients with KIAA0101-positive expression suffered
worse disease-free survival (HR, 3.64, P < 0.001), and in multivariate analysis
KIAA0101 retained its independent prognostic significance. Survival analysis
showed that GRHL2- and KIAA0101-positive patients had significantly lower disease
free survival (P = 0.002 and P < 0.001). We also found that KIAA0101 silencing
decreased kidney cancer cell migration and invasion in vitro. CONCLUSIONS: Using
an integrative system biology approach, we identified 3 novel factors as
potential biomarkers (AHR, GRHL2 and KIAA0101) involved in ccRCC pathogenesis and
not linked to kidney cancer before.
PMID- 25139458
TI - Phosphine-catalyzed annulations of 4,4-dicyano-2-methylenebut-3-enoates with
maleimides and maleic anhydride.
AB - A novel phosphine-catalyzed [4+1] annulation of maleimides with 4,4-dicyano-2
methylenebut-3-enoates has been developed to afford spirocyclic products, and the
maleimides serves as C1 synthons. Moreover, a phosphine-catalyzed formal [3+2]
annulation between 4,4-dicyano-2-methylenebut-3-enoates and maleic anhydride has
been also achieved, and maleic anhydride behaved as a C3 synthon in the
reaction, thus efficiently affording the functionalized cyclopentenones. A stable
phosphinium-containing zwitterionic compound is the key reactive intermediate in
both annulations and was successfully isolated. Plausible mechanisms have been
proposed on the basis of control experiments and deuterium-labeling experiments.
PMID- 25139459
TI - Synthesis and characterization of a novel second-order nonlinear optical
chromophore based on a new julolidine donor.
AB - A new chromophore HK containing the cis,cis-1,7-diethoxy-3-isopropyljulolidine
group as a novel electron-donor, thiophene as a pi-conjugated bridge and a
tricyanofuran (TCF) acceptor has been synthesized and systematically investigated
in this paper. Its corresponding chromophore FTC using 4-(diethyl amino)benzyl as
the electron donor group was also prepared for comparison. This is the first time
that the cis,cis-1,7-diethoxy-3-isopropyljulolidine group was introduced into NLO
materials. Density functional theory (DFT) was used to calculate the HOMO-LUMO
energy gap and first-order hyperpolarizability (beta) of the new chromophore. The
HOMO-LUMO gap was also investigated by cyclic voltammetry (CV). Upon using the
cis,cis-1,7-diethoxy-3-isopropyljulolidine group as the donor, a reduced energy
gap of 1.007 eV was obtained compared with chromophore FTC (DeltaE = 1.529 eV).
The high molecular hyperpolarizability of the new chromophore can be effectively
translated into large electro-optic (EO) coefficients (r33) in poled polymers.
The doped films containing the new chromophore HK showed a value of 72 pm V(-1)
at the concentration of 25 wt% at 1310 nm. This value is almost two times higher
than the EO activity of the usually reported traditional (N,N-diethyl) aniline
nonlinear optical (NLO) chromophore FTC. High r33 values indicated that the new
julolidine donor can efficiently improve the electron-donating ability and reduce
intermolecular electrostatic interactions, thus enhancing the macroscopic EO
activity. These properties, together with good solubility, suggest the potential
use of the new chromophore in advanced materials devices.
PMID- 25139460
TI - Effect of ERK1/2 signaling pathway in electro-acupuncture mediated up-regulation
of heme oxygenase-1 in lungs of rabbits with endotoxic shock.
AB - BACKGROUND: The anti-oxidative and anti-inflammatory activities of electro
acupuncture (EA), a traditional clinical method, are widely accepted, but its
mechanisms are not yet well defined. In this study, we investigated the role of
extracellular signal-regulated kinases1/2 (ERK1/2) pathways on electro
acupuncture - mediated up-regulation of heme oxygenase-1 (HO-1) in rabbit lungs
injured by LPS-induced endotoxic shock. MATERIAL/METHODS: Seventy rabbits were
randomly divided into 7 groups: group C, group M, group D, group SEAM, group EAM,
group EAMPD, and group PD98059. Male New England white rabbits were given EA
treatment on both sides once a day on days 1-5, and then received LPS to
replicate the experimental model of injured lung induced by endotoxic shock.
Then, they were killed by exsanguination at 6 h after LPS administration. The
blood samples were collected for serum examination, and the lungs were removed
for pathology examination, determination of wet-to-dry weight ratio, MDA content,
SOD activity, serum tumor necrosis factor-alpha, determination of HO-1 protein
and mRNA expression, and determination of ERK1/2 protein. RESULTS: The results
revealed that after EA treatment, expression of HO-1and ERK1/2 was slightly
increased compared to those in other groups, accompanied with less severe lung
injury as indicated by lower index of lung injury score, lower wet-to-dry weight
ratio, MDA content, and serum tumor necrosis factor-alpha levels, and greater SOD
activity (p<0.05 for all). After pretreatment with ERK1/2 inhibitor PD98059, the
effect of EA treatment and expression of HO-1 were suppressed (p<0.05 for all).
CONCLUSIONS: After electro-acupuncture stimulation at ST36 and BL13, severe lung
injury during endotoxic shock was attenuated. The mechanism may be through up
regulation of HO-1, mediated by the signal transductions of ERK1/2 pathways.
Thus, the regulation of ERK1/2 pathways via electro-acupuncture may be a
therapeutic strategy for endotoxic shock.
PMID- 25139462
TI - Novel strategies for preventing diabetes and obesity complications with natural
polyphenols.
AB - During the last years, the list of resveratrol effects has grown in parallel with
the number of other members of the polyphenol family described to modulate
glucose or lipid handling. In the same time, more than ten human studies on the
influence of resveratrol supplementation on two related metabolic diseases,
obesity and diabetes, have indicated that impressive beneficial effects co-exist
with lack of demonstration of clinical relevance, irrespective of the daily dose
ingested (0.075 to 1.5 g per capita) or the number of studied patients. Such
contrasting observations have been proposed to depend on the degree of insulin
resistance of the patients incorporated in the study. To date, no definitive
conclusion can be drawn on the antidiabetic or antiobesity benefits of
resveratrol. On the opposite, studies on animal models of diabesity consistently
indicated that resveratrol impairs diverse insulin actions in adipocytes,
blunting glucose transport, lipogenesis and adipogenesis. Since resveratrol also
favours lipolysis and limits the production of proinflammatory adipokines, its
administration in rodents results in limitation of fat deposition, activation of
hexose uptake into muscle, improvement of insulin sensitivity, and facilitation
of glucose disposal. Facing to a somewhat disappointing extrapolation to man of
these promising antidiabetic and antiobesity properties, attention must be paid
to re-examine resveratrol targets, especially those attainable after polyphenol
ingestion and to re-define the responses to low doses. In this context, human
adipocytes are proposed as a convenient model for the screening of "novel"
polyphenols that can reproduce, out class, or reinforce resveratrol metabolic
actions, Moreover, the use of combination of polyphenols is proposed to treat
diabesity complications in view of recently reported synergisms. Lastly,
multidisciplinar approaches are recommended for future investigations,
considering the wide range of polyphenol actions that induce body fat reduction,
liver disease mitigation, muscle function improvement, cardiovascular and renal
protection.
PMID- 25139461
TI - Telocytes subtypes in human urinary bladder.
AB - Urinary bladder voiding is a complex mechanism depending upon interplay among
detrusor, urothelium, sensory and motor neurons and connective tissue cells. The
identity of some of the latter cells is still controversial. We presently
attempted to clarify their phenotype(s) in the human urinary bladder by
transmission electron microscopy (TEM) and immunohistochemistry. At this latter
aim, we used CD34, PDGFRalpha, alphaSMA, c-Kit and calreticulin antibodies. Both,
TEM and immunohistochemistry, showed cells that, sharing several telocyte (TC)
characteristics, we identified as TC; these cells, however, differed from each
other in some ultrastructural features and immunolabelling according to their
location. PDGFRalpha/calret-positive, CD34/c-Kit-negative TC were located in the
sub-urothelium and distinct in two subtypes whether, similarly to myofibroblasts,
they were alphaSMA-positive and had attachment plaques. The sub-urothelial TC
formed a mixed network with myofibroblasts and were close to numerous nerve
endings, many of which nNOS-positive. A third TC subtype, PDGFRalpha/alphaSMA/c
Kit-negative, CD34/calret-positive, ultrastructurally typical, was located in the
submucosa and detrusor. Briefly, in the human bladder, we found three TC
subtypes. Each subtype likely forms a network building a 3-D scaffold able to
follow the bladder wall distension and relaxation and avoiding anomalous wall
deformation. The TC located in the sub-urothelium, a region considered a sort of
sensory system for the micturition reflex, as forming a network with
myofibroblasts, possessing specialized junctions with extracellular matrix and
being close to nerve endings, might have a role in bladder reflexes. In
conclusions, the urinary bladder contains peculiar TC able to adapt their
morphology to the organ activity.
PMID- 25139463
TI - Return to football and long-term clinical outcomes after thumb ulnar collateral
ligament suture anchor repair in collegiate athletes.
AB - PURPOSE: To evaluate return to play after complete thumb ulnar collateral
ligament (UCL) injury treated with suture anchor repair for both skill position
and non-skill position collegiate football athletes and report minimum 2-year
clinical outcomes in this population. METHODS: For this retrospective study,
inclusion criteria were complete rupture of the thumb UCL and suture anchor
repair in a collegiate football athlete performed by a single surgeon who used an
identical technique for all patients. Data collection included chart review,
determination of return to play, and Quick Disabilities of the Arm, Shoulder, and
Hand (QuickDASH) outcomes. RESULTS: A total of 18 collegiate football athletes
were identified, all of whom were evaluated for follow-up by telephone, e-mail,
or regular mail at an average 6-year follow-up. Nine were skill position players;
the remaining 9 played in nonskill positions. All players returned to at least
the same level of play. The average QuickDASH score for the entire cohort was 1
out of 100; QuickDASH work score, 0 out of 100; and sport score, 1 out of 100.
Average time to surgery for skill position players was 12 days compared with 43
for non-skill position players. Average return to play for skill position players
was 7 weeks postoperatively compared with 4 weeks for non-skill position players.
There was no difference in average QuickDASH overall scores or subgroup scores
between cohorts. CONCLUSIONS: Collegiate football athletes treated for thumb UCL
injuries with suture anchor repair had quick return to play, reliable return to
the same level of activity, and excellent long-term clinical outcomes. Skill
position players had surgery sooner after injury and returned to play later than
non-skill position players, with no differences in final level of play or
clinical outcomes. Management of thumb UCL injuries in collegiate football
athletes can be safely and effectively tailored according to the demands of the
player's football position. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
PMID- 25139464
TI - Constrained postures and spatial S-R compatibility as measured by the Simon
effect.
AB - Whereas working under constrained postures is known to influence the worker's
perceived comfort and health, little is known in regard to its influence on
performance. Employing an Auditory Simon task while varying posture, we
investigated the relationship between constrained postures and cognitive
processes in three experiments. In Experiment 1 and 2, participants operated a
rocker switch or a control knob with one hand either in front or in the back of
their body and while either sitting or kneeling. Perceived musculoskeletal
exertion was gathered with a questionnaire. Results of the first two experiments
showed differently perceived comfort and a minor effect of constrained posture on
cognitive performance. However, results indicated that spatial coding in the back
compares to either a virtual turn of the observer towards the control device
(front-device coding) or along the observer's hand (effector coding). To clarify
this issue the rocker switch was operated with one or two hands in Experiment 3,
showing a comparable coding only in the one-hand condition and indicating
evidence for the effector-coding hypothesis in the back.
PMID- 25139465
TI - Percutaneous Coronary Intervention in Spontaneous Coronary Artery Dissection:
Role of Intravascular Ultrasound.
AB - Spontaneous coronary artery dissection (SCAD) is a rare, life-threatening
condition that usually manifests as an acute myocardial infarction. Diagnosing
SCAD with conventional coronary angiogram can be challenging, particularly if the
true lumen is severely narrowed. Our case highlights the challenges in performing
successful percutaneous coronary intervention (PCI) in patients with SCAD.
Intravascular ultrasound can prove to be a pivotal tool in the diagnosis and
successful management of such cases by establishing the anatomic site of
dissection, and confirming stent placement in the true lumen following PCI.
PMID- 25139466
TI - Os(II) phosphors with near-infrared emission induced by ligand-to-ligand charge
transfer transition.
AB - Heating of Os3(CO)12 with 6 equiv of 2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5
yl) pyridine (fptzH) in refluxing diethylene glycol monomethyl ether, followed by
sequential treatment with stoichiometric Me3NO and addition of PPhMe2, afforded
two isomeric mixtures of red-emitting [Os(fptz)2(PPhMe2)2] (1T and 1C), for which
the notations T and C stand for the trans and cis-oriented fptz chelates,
respectively. Alternatively, preparation of Os(II) complex using a 1:1 mixture of
5,5'-di(trifluoromethyl)-3,3'-di-1,2,4-triazole (dttzH2) and 2,2'-bipyridine
(bpy), instead of fptzH, gave isolation of a mononuclear Os(II) complex
[Os(bpy)(dttz)(CO)2] (2) in moderate yield. Replacement of CO with PPhMe2 on 2
afforded near-infrared (NIR)-emitting Os(II) complex [Os(bpy)(dttz)(PPhMe2)2]
(3). The single-crystal X-ray structural analyses were executed on 1C, 2, and 3
to reveal the structural influence imposed by the various chelates. The
photophysical and electrochemical properties were measured and discussed using
the results of density functional theory (DFT) and time-dependent DFT
calculations. Complex 3 is selected as the dopant to probe its electroluminescent
properties by fabrication of the NIR emitting organic light-emitting diodes.
PMID- 25139467
TI - Single-item measures for depression and anxiety: Validation of the Screening Tool
for Psychological Distress in an inpatient cardiology setting.
AB - BACKGROUND: Depression and anxiety are common among patients with cardiovascular
disease (CVD) and confer significant cardiac risk, contributing to CVD morbidity
and mortality. Unfortunately, due to the lack of screening tools that address the
specific needs of hospitalized patients, few cardiac inpatient programs offer
routine screening for these forms of psychological distress, despite
recommendations to do so. AIMS: The purpose of this study was to validate single
item measures for depression and anxiety among cardiac inpatients. METHODS:
Consecutive inpatients were recruited from the cardiology and cardiac surgery
step-down units at a university-affiliated, quaternary-care hospital. Subjects
completed a questionnaire that included: (a) demographics, (b) single-item
measures for depression and anxiety (from the Screening Tool for Psychological
Distress (STOP-D)), and (c) Hospital Anxiety and Depression Scale (HADS).
RESULTS: One hundred and five participants were recruited with a wide variety of
cardiac diagnoses, having a mean age of 66 years, and 28% were women. Both STOP-D
items were highly correlated with their corresponding validated measures and
demonstrated robust receiver-operator characteristic curves. Severity scores on
both items correlated well with established severity cut-off scores on the
corresponding subscales of the HADS. CONCLUSIONS: The STOP-D is a self
administered, self-report measure using two independent items that provide
severity scores for depression and anxiety. The tool performs very well compared
with other previously validated measures. Requiring no additional scoring and
being free, STOP-D offers a simple and valid method for identifying hospitalized
cardiac patients who are experiencing psychological distress. This crucial first
step triggers initiation of appropriate monitoring and intervention, thus
reducing the likelihood of the adverse cardiac outcomes associated with
psychological distress.
PMID- 25139468
TI - The importance of interactions between patients and healthcare professionals for
heart failure self-care: A systematic review of qualitative research into patient
perspectives.
AB - BACKGROUND: Effective heart failure (HF) self-care can improve clinical outcomes
but is dependent on patients' undertaking a number of complex self-care
behaviors. Research into the effectiveness of HF management programs demonstrates
mixed results. There is a need to improve understanding of patient perspectives'
of self-care need in order to enhance supportive interventions. AIM: This paper
reports selected findings from a systematic review of qualitative research
related to HF self-care need from the patients' perspective. The focus here is on
those facets of patient-healthcare professional relationships perceived by
patients to influence HF self-care. METHOD: We searched multiple healthcare
databases to identify studies reporting qualitative findings with extractable
data related to HF self-care need. Joanna Briggs Institute systematic review
methods were employed and recognized meta-synthesis techniques were applied.
Critical realist theory provided analytical direction to highlight how individual
and contextual factors came together in complex ways to influence behavior and
outcomes. RESULTS: Altogether 24 studies (1999-2012) containing data on patient
healthcare professional relationships and HF self-care were included. Interaction
with healthcare professionals influenced self-care strongly but was notably mixed
in terms of reported quality. Effective HF self-care was more evident when
patients perceived that their healthcare professional was responsive, interested
in their individual needs, and shared information. Poor communication and lack of
continuity presented common barriers to HF self-care. CONCLUSION: Interactions
and relationships with clinicians play a substantial role in patients' capacity
for HF self-care. The way healthcare professionals interact with patients
strongly influences patients' understanding about their condition and self-care
behaviors.
PMID- 25139469
TI - Covariate measurement error correction methods in mediation analysis with failure
time data.
AB - Mediation analysis is important for understanding the mechanisms whereby one
variable causes changes in another. Measurement error could obscure the ability
of the potential mediator to explain such changes. This article focuses on
developing correction methods for measurement error in the mediator with failure
time outcomes. We consider a broad definition of measurement error, including
technical error, and error associated with temporal variation. The underlying
model with the "true" mediator is assumed to be of the Cox proportional hazards
model form. The induced hazard ratio for the observed mediator no longer has a
simple form independent of the baseline hazard function, due to the conditioning
event. We propose a mean-variance regression calibration approach and a follow-up
time regression calibration approach, to approximate the partial likelihood for
the induced hazard function. Both methods demonstrate value in assessing
mediation effects in simulation studies. These methods are generalized to
multiple biomarkers and to both case-cohort and nested case-control sampling
designs. We apply these correction methods to the Women's Health Initiative
hormone therapy trials to understand the mediation effect of several serum sex
hormone measures on the relationship between postmenopausal hormone therapy and
breast cancer risk.
PMID- 25139470
TI - Utilization of Zwitterion-based solutions to dissect the relative effects of
solution pH and ionic strength on the aggregation behavior and conformational
stability of a fusion protein.
AB - Solution pH and ionic strength (I) have complex effects on protein stability. We
developed an experimental approach based on exploitation of the zwitterionic
characteristic of amino acid molecules to probe the relative contribution from
each. A variety of types of amino acid solutions were adopted to investigate the
effects of pH and I in a manner that allows independent evaluation of each
factor. The same effect could not be achieved using conventional buffer
solutions. Size-exclusion chromatography, capillary differential scanning
calorimetry, and fluorescence spectroscopy were utilized to probe the protein
aggregation and conformation. The results suggested that, in addition to pH,
solution ionic strength as a function of ionization state of the amino acid
molecules and the ions introduced by pH adjustment played an important role in
the aggregation and conformation of the protein studied. This experimental
approach offers a useful tool to aid fundamental understanding of the relative
effects of solution pH and ionic strength on protein stability.
PMID- 25139471
TI - Using (18)F-FLT PET to distinguish between malignant and benign breast lesions
with suspicious findings in mammography and breast ultrasound.
AB - PURPOSE: To investigate the diagnostic performance of 3'-deoxy-3'
[(18)F]fluorothymidine ((18)F-FLT) PET in women with suspicious breast findings
on conventional imaging (mammography and breast ultrasound). METHODS: Twenty
eight women with suspicious findings on conventional imaging were enrolled. A
whole-body PET/CT in the supine position (first PET) was performed 60 min after
intravenous injection of 0.07 mCi/kg (18)F-FLT, followed by a regional PET of the
breast in the prone position (second PET). For each lesion, the SUVmax of the
first PET (SUV1) and second PET (SUV2) were measured. For the receiver operating
characteristic (ROC) analysis of the diagnostic parameters, of the cutoff points
with sensitivities >90 %, we chose the one with highest specificity as the
optimal cutoff point to obtain the corresponding sensitivity and specificity.
RESULTS: A total of 34 breast lesions (21 benign, 13 malignant) were analyzed.
The SUV1 and SUV2 of the malignant lesions (median values 4.6 vs. 4.4,
respectively) were higher than those of the benign lesions that had medians of
1.2 and 1.0, respectively (P = 0.0001). The area under the ROC curve (AUC) of
SUV1 (0.905) showed no significant difference from that of SUV2 (0.912) (P =
0.77). The sensitivity and specificity using SUV1 = 1.24 as cutoff were 92.3 and
52.4 %, and those using SUV2 = 1.5 as cutoff were 92.3 and 66.7 %, respectively.
CONCLUSION: (18)F-FLT PET showed acceptable diagnostic performance for suspicious
breast findings on conventional imaging, and SUV2 showed higher specificity than
SUV1.
PMID- 25139472
TI - 68Gallium- and 90Yttrium-/ 177Lutetium: "theranostic twins" for diagnosis and
treatment of NETs.
AB - Abundant expression of somatostatin receptors (SSTR) is frequently identified in
differentiated neuroendocrine tumors and may serve as potential target for
diagnostic imaging and treatment. This article discusses the "theranostic
approach" of SSTR-targeting compounds including an overview of its role for
diagnosis, staging and restaging, discussing its way to being established in
clinical routine, and giving an outlook about further potentially relevant
developments.
PMID- 25139473
TI - Glucose control and diabetic neuropathy: lessons from recent large clinical
trials.
AB - Diabetic peripheral and autonomic neuropathies are common complications of
diabetes with broad spectrums of clinical manifestations and high morbidity.
Studies using various agents to target the pathways implicated in the development
and progression of diabetic neuropathy were promising in animal models. In
humans, however, randomized controlled studies have failed to show efficacy on
objective measures of neuropathy. The complex anatomy of the peripheral and
autonomic nervous systems, the multitude of pathogenic mechanisms involved, and
the lack of uniformity of neuropathy measures have likely contributed to these
failures. To date, tight glycemic control is the only strategy convincingly shown
to prevent or delay the development of neuropathy in patients with type 1
diabetes and to slow the progression of neuropathy in some patients with type 2
diabetes. Lessons learned about the role of glycemic control on distal
symmetrical polyneuropathy and cardiovascular autonomic neuropathy are discussed
in this review.
PMID- 25139474
TI - Lossless data compression for improving the performance of a GPU-based
beamformer.
AB - The powerful parallel computation ability of a graphics processing unit (GPU)
makes it feasible to perform dynamic receive beamforming However, a real time GPU
based beamformer requires high data rate to transfer radio-frequency (RF) data
from hardware to software memory, as well as from central processing unit (CPU)
to GPU memory. There are data compression methods (e.g. Joint Photographic
Experts Group (JPEG)) available for the hardware front end to reduce data size,
alleviating the data transfer requirement of the hardware interface.
Nevertheless, the required decoding time may even be larger than the transmission
time of its original data, in turn degrading the overall performance of the GPU
based beamformer. This article proposes and implements a lossless compression
decompression algorithm, which enables in parallel compression and decompression
of data. By this means, the data transfer requirement of hardware interface and
the transmission time of CPU to GPU data transfers are reduced, without
sacrificing image quality. In simulation results, the compression ratio reached
around 1.7. The encoder design of our lossless compression approach requires low
hardware resources and reasonable latency in a field programmable gate array. In
addition, the transmission time of transferring data from CPU to GPU with the
parallel decoding process improved by threefold, as compared with transferring
original uncompressed data. These results show that our proposed lossless
compression plus parallel decoder approach not only mitigate the transmission
bandwidth requirement to transfer data from hardware front end to software system
but also reduce the transmission time for CPU to GPU data transfer.
PMID- 25139475
TI - Lipopolysaccharide-induced sickness behavior in lactating rats decreases
ultrasonic vocalizations and exacerbates immune system activity in male
offspring.
AB - OBJECTIVE: The present study analyzed the effects of lipopolysaccharide (LPS) on
maternal behavior during lactation and possible correlations with changes in
emotional and immune responses in offspring. METHODS: Lactating rats received 100
MUg/kg LPS, and the control group received saline solution on lactation day (LD)
3. Maternal general activity and maternal behavior were observed on LD5 (i.e. the
day that the peak of fever occurred). In male pups, hematological parameters and
ultrasonic vocalizations (USVs) were assessed on LD5. At weaning, an additional
dose of LPS (50 ug/kg, i.p.) was administered in male pups, and open-field
behavior, oxidative burst and phagocytosis were evaluated. RESULTS: A reduction
in the time in which dams retrieved the pups was observed, whereas no effects on
maternal aggressive behavior were found. On LD5, a reduction of the frequency of
USVs was observed in pups, but no signs of inflammation were found. At weaning,
an increase in immune system activity was observed, but no differences in open
field behavior were found. CONCLUSION: These results indicate that inflammation
in lactating mothers disrupted mother/pup interactions and may have produced
short- and long-term effects on pup behavior as well as biological pathways that
modulate inflammatory responses to bacterial endotoxin challenge in pups.
PMID- 25139476
TI - Rescue balloon dilation of the ampulla for retrieving an impacted biliary
extraction basket.
PMID- 25139477
TI - Are perfluoroalkyl acids in waste water treatment plant effluents the result of
primary emissions from the technosphere or of environmental recirculation?
AB - Wastewater treatment plants (WWTP) have been suggested to be one of the major
pathways of perfluoroalkyl acids (PFAAs) from the technosphere to the aquatic
environment. The origin of PFAAs in WWTP influents is either from current primary
emissions or a result of recirculation of PFAAs that have been residing and
transported in the environment for several years or decades. Environmental
recirculation can then occur when PFAAs from the environment enter the wastewater
stream in, e.g., tap water. In this study 13 PFAAs and perfluorooctane
sulfonamide were analyzed in tap water as well as WWTP influent, effluent and
sludge from three Swedish cities: Bromma (in the metropolitan area of Stockholm),
Bollebygd and Umea. A mass balance of the WWTPs was assembled for each PFAA.
Positive mass balances were observed for PFHxA and PFOA in all WWTPs, indicating
the presence of precursor compounds in the technosphere. With regard to
environmental recirculation, tap water was an important source of PFAAs to the
Bromma WWTP influent, contributing >40% for each quantified sulfonic acid and up
to 30% for the carboxylic acids. The PFAAs in tap water from Bollebygd and Umea
did not contribute significantly to the PFAA load in the WWTP influents. Our
results show that in order to estimate current primary emissions from the
technosphere, it may be necessary to correct the PFAA emission rates in WWTP
effluents for PFAAs present in tap water, especially in the case of elevated
levels in tap water.
PMID- 25139478
TI - [Aneurysms of the thoracic and thoracoabdominal aorta].
AB - The incidence and operations of thoracic and thoracoabdominal aortic aneurysms
have significantly increased. The indications for repair are considered to be a
diameter of 6 cm or more and 5.5 cm for patient groups with increased risk of
rupture. Complex open surgical repair is associated with significant mortality
and complication rates. Total or hybrid endovascular repair seems to reduce early
postoperative complications and mortality. The endovascular approach has evolved
to be a good and predominant alternative to open repair of these aneurysms for
older and high-risk patients as well as for aneurysms with optimal morphological
suitability. Notwithstanding, at present a complete paradigm shift from open to
endovascular repair for all patients, especially those with complex aneurysms,
cannot yet be established.
PMID- 25139479
TI - [Transvaginal cholecystectomy: results of a randomized study].
AB - BACKGROUND: Transvaginal cholecystectomy (TVC) is regarded as a model operation
in the newly developed field of natural orifice transluminal endoscopic surgery
(NOTES). Randomized, controlled trials to assess TVC as a surgical strategy are
largely missing. MATERIALS AND METHODS: The study was a double blind, randomized,
controlled, single center trial in female patients > 18 years with symptomatic
cholecystolithiasis comparing laparoscopic cholecystectomy (CLC) and TVC. The
study investigated pain reduction of >= 1 point on a visual-numeric rating scale
with a follow-up after 7 days. Secondary endpoints were complications and patient
reported outcome. Groups were established using computer-generated randomization
and sealed envelopes in the operating theatre. At the end of the surgical
procedure all patients received a standard 4-trocar dressing as for CLC and a
vaginal tamponade. RESULTS: A total of 426 patients were asked to participate, of
which 97 were randomized, 51 in the CLC, 41 in the TVC groups and 5 were excluded
from the study. Patients were comparable regarding age, body mass index (BMI) and
American Society of Anesthesiologists (ASA) grade. Surgical and anesthesia times
were significantly different. There was no difference in postoperative pain. The
majority of patients were satisfied with both procedures and TVC was recommended
to other patients by 93 % of patients in the TVC group. CONCLUSION: The results
did not show superiority of TVC over CLC with regards to postoperative pain. With
no differences in postoperative pain and high patient satisfaction, TVC can be
recommended to future patients as an alternative method. For confirmation of this
evaluation of TVC further randomized trials are needed.
PMID- 25139481
TI - Regulation of insulin on lipid metabolism in freshly isolated hepatocytes from
yellow catfish (Pelteobagrus fulvidraco).
AB - Although the metabolic actions of insulin in fish have been investigated widely
in the past years, the regulatory effect of insulin on lipid metabolism has
received little attention, especially in primary hepatocytes of fish. In the
present study, freshly hepatocytes were isolated from yellow catfish, cultured
and subjected to different insulin levels (0, 10, 100 and 1000nM) for 0h, 24h and
48h. Triglyceride (TG) content, activity and expression of several key enzymes
involved in lipid metabolism, as well as mRNA levels of key transcription factors
related to lipid metabolism, were assessed at 0h, 24h and 48h, respectively.
Insulin incubation tended to increase the activities and expression of several
lipogenic enzymes (such as FAS, G6PD, 6PGD). However, reduced CPT I gene
expression was observed in hepatocytes following incubation treatment. Insulin
administration also tended to up-regulate SREBP-1 expression but down-regulate
PPARalpha mRNA levels. Insulin incubation enhanced lipogenesis and reduced
lipolysis of freshly isolated hepatocytes of yellow catfish, in coincidence with
increased TG content. Pearson correlations between expression of SREBP-1 and
PPARalpha, and expression and activity of several enzymes were also observed,
especially at 48-h insulin incubation. To the best of our knowledge, this is the
first to study the effects of insulin on lipogenesis and lipolysis at both
transcriptional and enzymatic levels using primary hepatocytes culture model in
fish, which will help to understand the regulation of lipid metabolism by insulin
in vivo, and will give us new insight into the insulin role in nutrient
metabolism in fish.
PMID- 25139482
TI - The strong relation between post-hemodialysis blood methylglyoxal levels and post
hemodialysis blood glucose concentration rise.
AB - BACKGROUND: Hemodialysis is known to decrease blood glucose concentration (BGC),
insulin, and methylglyoxal levels. However, the effects of decreases in these
factors on the increase in post-hemodialysis BGC remain unknown. This study
identifies the effects of hemodialysis-induced changes in concentrations of these
elements on post-hemodialysis BGC. METHODS: Study subjects included seventeen
insulin-treated diabetes patients receiving hemodialysis. The fluctuations in BGC
on hemodialysis-treatment days and non-hemodialysis-treatment days were evaluated
using a continuous glucose monitoring system. BGC was evaluated before breakfast,
before starting hemodialysis, at the end of hemodialysis, 1 h post-hemodialysis
(lunch), and 6 h post-hemodialysis (dinner). BGC, insulin, and methylglyoxal
levels were measured at the start and end of hemodialysis. This study also
evaluated the changes in the concentrations of glucose and insulin in the
arterial line and the venous line during hemodialysis. RESULTS: Hemodialysis
decreases BGC, insulin, and methylglyoxal levels. Concentrations of glucose and
insulin in the arterial line gradually decreased during dialysis, while
concentrations in the venous line approached their original concentrations in the
dialysis solution. BGC rose sharply after eating lunch 1 h post-hemodialysis. The
blood glucose, insulin, and methylglyoxal concentrations at the end of
hemodialysis were associated with the M values and the mean amplitude of glycemic
excursion values between before lunch and dinner. In particular, methylglyoxal
concentration at the end of hemodialysis was strongly related to the post
hemodialysis increase in BGC. CONCLUSION: Hemodialysis-induced decreases in
methylglyoxal concentrations and methylglyoxal concentration at the end of
hemodialysis influence post-hemodialysis fluctuations in BGC.
PMID- 25139483
TI - Early life seizures in female rats lead to anxiety-related behavior and abnormal
social behavior characterized by reduced motivation to novelty and deficit in
social discrimination.
AB - Previously, we demonstrated that male Wistar rats submitted to neonatal status
epilepticus showed abnormal social behavior characterized by deficit in social
discrimination and enhanced emotionality. Taking into account that early insult
can produce different biological manifestations in a gender-dependent manner, we
aimed to investigate the social behavior and anxiety-like behavior in female
Wistar rats following early life seizures. Neonate female Wistar rats at 9 days
postnatal were subject to pilocarpine-induced status epilepticus and the control
received saline. Behavioral tests started from 60 days postnatal and were carried
out only during the diestrus phase of the reproductive cycle. In sociability test
experimental animals exhibited reduced motivation for social encounter and
deficit in social discrimination. In open field and the elevated plus maze,
experimental animals showed enhanced emotionality with no changes in basal
locomotor activity. The results showed that female rats submitted to neonatal
status epipepticus showed impaired social behavior, characterized by reduced
motivation to novelty and deficit in social discrimination in addition to
enhanced emotionality.
PMID- 25139484
TI - Exposure to static and time-varying magnetic fields from working in the static
magnetic stray fields of MRI scanners: a comprehensive survey in the Netherlands.
AB - Clinical and research staff who work around magnetic resonance imaging (MRI)
scanners are exposed to the static magnetic stray fields of these scanners.
Although the past decade has seen strong developments in the assessment of
occupational exposure to electromagnetic fields from MRI scanners, there is
insufficient insight into the exposure variability that characterizes routine MRI
work practice. However, this is an essential component of risk assessment and
epidemiological studies. This paper describes the results of a measurement survey
of shift-based personal exposure to static magnetic fields (SMF) (B) and motion
induced time-varying magnetic fields (dB/dt) among workers at 15 MRI facilities
in the Netherlands. With the use of portable magnetic field dosimeters, >400 full
shift and partial shift exposure measurements were collected among various jobs
involved in clinical and research MRI. Various full-shift exposure metrics for B
and motion-induced dB/dt exposure were calculated from the measurements,
including instantaneous peak exposure and time-weighted average (TWA) exposures.
We found strong correlations between levels of static (B) and time-varying
(dB/dt) exposure (r = 0.88-0.92) and between different metrics (i.e. peak
exposure, TWA exposure) to express full-shift exposure (r = 0.69-0.78). On
average, participants were exposed to MRI-related SMFs during only 3.7% of their
work shift. Average and peak B and dB/dt exposure levels during the work inside
the MRI scanner room were highest among technical staff, research staff, and
radiographers. Average and peak B exposure levels were lowest among cleaners,
while dB/dt levels were lowest among anaesthesiology staff. Although modest
exposure variability between workplaces and occupations was observed, variation
between individuals of the same occupation was substantial, especially among
research staff. This relatively large variability between workers with the same
job suggests that exposure classification based solely on job title may not be an
optimal grouping strategy for epidemiological purposes.
PMID- 25139485
TI - Single-nucleotide polymorphisms in the vascular endothelial growth factor pathway
and outcomes of patients treated with first-line cytotoxic chemotherapy combined
with bevacizumab for advanced colorectal cancer.
AB - OBJECTIVE: The aim of this study was to evaluate the association between the
efficacy of first-line cytotoxic chemotherapy plus bevacizumab and single
nucleotide polymorphisms (SNPs) of angiogenic genes in patients with advanced
colorectal cancer (CRC). METHODS: DNA was extracted from blood samples of 125
patients, and 12 SNPs were evaluated for association with the objective response
rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS:
The vascular endothelial growth factor A (VEGFA) rs833061 T/T was associated with
superior ORR compared to its alternative genotypes (75.9 vs. 50.8%; p = 0.008),
and the interleukin 8 rs4073 A/A genotype tended to be associated with poor ORR
(45.0 vs. 66.0%; p = 0.067). The median PFS and OS were superior in patients with
the fms-related tyrosine kinase 1 (FLT1) rs9513070 A/A genotype (8.7 vs. 6.6
months; p = 0.001 and 26.4 vs. 16.1 months; p = 0.038, respectively). The kinase
insert domain receptor rs1531289 G/G genotype tended to be associated with
improved PFS (8.0 vs. 7.1 months; p = 0.069). In haplotype analysis, the FLT1
rs9513070/rs9554320/rs9582036 GCA haplotype was associated with inferior PFS and
OS (p = 0.004 and p = 0.041, respectively). CONCLUSION: The VEGFA rs833061 SNP is
associated with the ORR, and the FLT1 rs9513070 SNP and FLT1 GCA haplotypes are
associated with PFS and OS in advanced CRC patients treated with cytotoxic
chemotherapy plus bevacizumab.
PMID- 25139486
TI - Stroke care continues to show "unacceptable variation," audit finds.
PMID- 25139487
TI - Systemic exposure of topical erythromycin in comparison to oral administration
and the effect on cytochrome P450 3A4 activity.
AB - AIMS: Erythromycin is a macrolide antibiotic, which is frequently used as a
topical formulation for the treatment of acne. It is also known as an inhibitor
of the cytochrome P450 (CYP) isoenzyme 3A4. In this study, the systemic
availability of topical erythromycin, hence the influence on the activity of
CYP3A, is evaluated in comparison to orally administered erythromycin. METHODS:
Sixteen healthy volunteers received consecutively topical (two applications of
800 mg) and oral erythromycin (two dose groups, 250 and 1000 mg, with n = 8) to
assess erythromycin pharmacokinetics. A microdose of midazolam (3 MUg orally) was
used to determine the effect on CYP3A activity. RESULTS: After topical
administration, erythromycin was detected in the plasma of every participant
without causing a statistically significant alteration of CYP3A activity. After
oral administration, the dose-normalized erythromycin exposure (AUCinfinity ) was
1335 h ng ml(-1) after 250 mg and 3-fold higher after the 1000 mg dose (4051 h ng
ml(-1); P < 0.01), suggesting nonlinear pharmacokinetics of erythromycin. Both
oral doses inhibited CYP3A activity; midazolam clearance was decreased to 61%
(250 mg) and 21% (1000 mg). The relationship between erythromycin exposure and
CYP3A activity (Hill equation) revealed a 50% reduction of CYP3A activity by an
erythromycin AUCinfinity of 2106 h ng ml(-1). CONCLUSIONS: Topical erythromycin
did not cause clinically relevant CYP3A alterations, although low systemic
availability of erythromycin was observed. This supports the assumption that
treatment with topical erythromycin is not critical in terms of CYP3A inhibition.
Furthermore, substantial nonlinearity of erythromycin pharmacokinetics after two
different oral doses was observed, possibly due to autoinhibition.
PMID- 25139488
TI - What are the pharmacotherapy options for treating prediabetes?
AB - INTRODUCTION: The incidence of type 2 diabetes mellitus (T2DM) has risen to
epidemic proportions, and this is associated with enormous cost. T2DM is preceded
by 'prediabetes', and the diagnosis of impaired glucose tolerance (IGT) and/or
impaired fasting glucose (IFG) provides an opportunity for targeted intervention.
Prediabetic subjects manifest both core defects characteristic of T2DM, that is,
insulin resistance and beta-cell dysfunction. Interventions which improve insulin
sensitivity and/or preserve beta-cell function are logical strategies to delay
the conversion of IGT/IFG to T2DM or revert glucose tolerance to normal. AREAS
COVERED: The authors examine pharmacologic agents that have proven to decrease
the conversion of IGT to T2DM and represent potential treatment options in
prediabetes. EXPERT OPINION: Weight loss improves whole body insulin sensitivity,
preserves beta-cell function and decreases progression of prediabetes to T2DM. In
real life long-term weight loss is the exception and, even if successful, 40 -
50% of IGT individuals still progress to T2DM. Pharmacotherapy provides an
alternative strategy to improve insulin sensitivity and preserve beta-cell
function. Thiazolidinediones (TZDs) are highly effective in T2DM prevention. Long
acting glucagon-like peptide-1 (GLP-1) analogs, because they augment beta-cell
function and promote weight loss, are effective in preventing IGT progression to
T2DM. Metformin is considerably less effective than TZDs or GLP-1 analogs.
PMID- 25139489
TI - Cellular distribution of Egr1 transcription in the male rat pituitary gland.
AB - The transcription factor gene Egr1 is necessary for female fertility; EGR1
protein is an established molecular regulator of adult female gonadotroph
function where it mediates GNRH-stimulated transcription of the Lhb gene. Recent
studies have also implicated pituitary EGR1 in the mediation of other
physiological signals indicating an integrative function. However, the role of
EGR1 in males is less well defined and this uncertainty is compounded by the
absence of cellular expression data in the male pituitary gland. The aim of this
study, therefore, was to define the distribution of Egr1 gene expression in the
adult male rat pituitary. To further this aim, we have evaluated cellular
populations in a transgenic rat model (Egr1-d2EGFP), in which we demonstrate
regulated green fluorescent protein (GFP) expression in EGR1+ pituitary cells.
Cellular filling by GFP enabled morphological and molecular differentiation of
different populations of gonadotrophs; Egr1 transcription and LHB were highly co
localised in a major population of large cells but only minimally co-localised in
small GFP+ cells; the latter cells were shown to be largely (80%) composed of
minority populations of GH+ somatotrophs (9% of total GH+) and PRL+ lactotrophs
(3% of total PRL+). Egr1 transcription was not found in TSH+, ACTH+ or SOX2+
precursor cells and was only minimally co-localised in S-100beta+
folliculostellate cells. Our demonstration that the Egr1 gene is actively and
selectively transcribed in a major sub-population of male LHB+ cells indicates a
largely conserved role in gonadotroph function and has provided a basis for
further defining this role.
PMID- 25139490
TI - 1,25-Vitamin D3 promotes cardiac differentiation through modulation of the WNT
signaling pathway.
AB - Cardiovascular disease (CVD) remains the leading cause of death worldwide. Low
levels of vitamin D are associated with high risk of myocardial infarction, even
after controlling for factors associated with coronary artery disease. A growing
body of evidence indicates that vitamin D plays an important role in CVD-related
signaling pathways. However, little is known about the molecular mechanism by
which vitamin D modulates heart development. The WNT signaling pathway plays a
pivotal role in tissue development by controlling stem cell renewal, lineage
selection and, even more importantly, heart development. In this study, we
examined the role of 1,25-D3 (the active form of vitamin D) on cardiomyocyte
proliferation, apoptosis, cell phenotype, cell cycle progression and
differentiation into cardiomyotubes. We determined that the addition of 1,25-D3
to cardiomyocytes cells: i) inhibits cell proliferation without promoting
apoptosis; ii) decreases expression of genes related to the regulation of the
cell cycle; iii) promotes formation of cardiomyotubes; iv) induces the expression
of casein kinase-1-alpha1, a negative regulator of the canonical WNT signaling
pathway; and v) increases the expression of the noncanonical WNT11, which it has
been demonstrated to induce cardiac differentiation during embryonic development
and in adult cells. In conclusion, we postulate that vitamin D promotes cardiac
differentiation through a negative modulation of the canonical WNT signaling
pathway and by upregulating the expression of WNT11. These results indicate that
vitamin D repletion to prevent and/or improve cardiovascular disorders that are
linked with abnormal cardiac differentiation, such as post infarction cardiac
remodeling, deserve further study.
PMID- 25139491
TI - Damnacanthal inhibits the NF-kappaB/RIP-2/caspase-1 signal pathway by inhibiting
p56lck tyrosine kinase.
AB - Damnacanthal is a major constituent of Morinda citrifolia L. (noni) and exhibits
anti-cancer and anti-inflammatory activities. However, the effects of
damnacanthal on allergic diseases have not been determined. In this study, we
investigated the effect of damnacanthal on mast cell-mediated allergic
inflammatory responses. Damnacanthal significantly and dose-dependently inhibited
compound 48/80-induced systemic anaphylactic shock, histamine release and
intracellular calcium levels. In particular, IgE-mediated passive cutaneous
anaphylaxis was significantly inhibited by the oral administration of
damnacanthal. In addition, we report for the first time that p56lck tyrosine
kinase was expressed in phorbol 12-myristate 13-acetate and calcium ionophore
A23187 (PMACI)-stimulated mast cells. Furthermore, damnacanthal inhibited the up
regulation of p56lck tyrosine kinase activity by PMACI and repressed PMACI
induced histidine decarboxylase expression and activity. Damnacanthal also
inhibited PMACI-induced interleukin (IL)-1beta, IL-6 and tumor necrosis factor
alpha expressions by suppressing nuclear factor-kappa B (NF-kappaB) activation
and suppressed the activation of caspase-1 and the expression of receptor
interacting protein-2. This study shows damnacanthal inhibits the NF
kappaB/receptor-interacting protein-2/caspase-1 signal pathway by inhibiting
p56lck tyrosine kinase and suggests that damnacanthal has potential for the
treatment of mast cell-mediated allergic disorders.
PMID- 25139492
TI - Monitoring the response of bone metastases to treatment with Magnetic Resonance
Imaging and nuclear medicine techniques: a review and position statement by the
European Organisation for Research and Treatment of Cancer imaging group.
AB - Assessment of the response to treatment of metastases is crucial in daily
oncological practice and clinical trials. For soft tissue metastases, this is
done using computed tomography (CT), Magnetic Resonance Imaging (MRI) or Positron
Emission Tomography (PET) using validated response evaluation criteria. Bone
metastases, which frequently represent the only site of metastases, are an
exception in response assessment systems, because of the nature of the fixed bony
defects, their complexity, which ranges from sclerotic to osteolytic and because
of the lack of sensitivity, specificity and spatial resolution of the previously
available bone imaging methods, mainly bone scintigraphy. Techniques such as MRI
and PET are able to detect the early infiltration of the bone marrow by cancer,
and to quantify this infiltration using morphologic images, quantitative
parameters and functional approaches. This paper highlights the most recent
developments of MRI and PET, showing how they enable early detection of bone
lesions and monitoring of their response. It reviews current knowledge, puts the
different techniques into perspective, in terms of indications, strengths,
weaknesses and complementarity, and finally proposes recommendations for the
choice of the most adequate imaging technique.
PMID- 25139493
TI - Prenatal Diagnosis of Infantile Myofibroma with Postnatal Imaging Correlation.
AB - Infantile myofibroma is the most common fibrous tumor in infancy. A majority of
these lesions are solitary and occur in the head and neck region. Unless visceral
sites are involved, the clinical course is typically benign. However, the
difficulty in these cases is the differentiation of a benign myofibroma from a
solitary malignant neoplasm and determination of visceral involvement. Prenatal
diagnosis of this condition is rarely described in the literature, but it does
indeed have a role in perinatal management. Our patient was initially identified
by prenatal ultrasound with fetal MRI for further characterization of the mass.
We present the case of a prenatally diagnosed solitary infantile myofibroma of
the lower extremity and highlight the role of prenatal imaging in the diagnosis
and treatment of this condition.
PMID- 25139494
TI - Glycogen phosphorylase BB in myocardial infarction.
AB - Early experimental and clinical reports on glycogen phosphorylase BB (GPBB)
kinetics following myocardial ischemic injury suggested that it could be a useful
diagnostic marker for early detection of acute myocardial infarction (AMI). After
more than two decades of investigation, there is now overwhelming body of
evidence that do not support the use of GPBB measurement in diagnosis of acute
AMI in patients presenting with acute chest pain. Currently, GPBB cannot be
recommended as a diagnostic marker of AMI either as a stand-alone test or as an
addition to (high-sensitive) troponin testing. It should be noted that these
considerations apply to the early diagnosis of AMI, not to the prognostic
stratification, which is also suggested but it warrants further investigation.
The aim of this review is to summarize available evidence of GPBB measurement in
early diagnosis of myocardial infarction.
PMID- 25139495
TI - Intra-day and inter-day biological variations of peripheral blood lymphocytes.
AB - BACKGROUND: The proportion and absolute numbers of lymphocyte subsets are
important indices that reflect the immunological status of the body. Few studies
on biological variations of absolute lymphocyte subset counts and no study in
Asian population are currently available. Furthermore, there have been few
reports on the biological variation of these indices in the short term. METHODS:
At 8:00AM, 12:00PM, and 4:00PM on days 1, 3, and 5, venous blood was collected
from 20 healthy volunteers. All participants maintained their normal lifestyles.
The percent and absolute lymphocyte subset counts were measured using single
platform method. RESULTS: Intraday and interday biological variations for the
absolute and percent counts of lymphocyte subsets were relatively constant. The
intra-individual coefficient of variation (CVI) and inter-individual coefficient
of variation (CVG) were similar to those in previous studies. Biological
variations in the percent and absolute counts for the CD3(+)CD4(-)CD8(-),
CD3(+)CD4(+)CD8(+), and CD3(+)CD16(+)CD56(+) subsets were relatively high.
CONCLUSIONS: These observations are clinically valuable. Investigation on the CVI
and CVG may allow us to determine the utility of traditional population based
reference ranges. Documentation of the reference change values may be used as
objective delta-check values in quality management and decide whether the change
that occur in an individual's serial results before the change is significant.
The present study also enriched the database regarding the biological variations
of lymphocyte subsets in Asian population.
PMID- 25139496
TI - Serum levels of soluble Fas ligand, granzyme B and cytochrome c during adjuvant
chemotherapy of breast cancer.
AB - BACKGROUND: Anticancer agents used in chemotherapy for tumors induce apoptosis in
malignant cells. Soluble Fas ligand, granzyme B and cytochrome c are key elements
in the process of apoptosis. The objective of this preliminary study was to
evaluate the changes in the serum concentrations of these parameters in breast
cancer patients undergoing adjuvant chemotherapy. MATERIALS AND METHODS: Sixty
patients with histopathologically proven breast cancer were included in the
present study. The blood samples were taken after surgery before chemotherapy and
after 3weeks of administration of the first cycle of chemotherapy. Thirty healthy
female controls were selected for comparison. Soluble FasL, granzyme B and
cytochrome c were estimated from serum by ELISA. RESULTS: Significantly increased
concentrations of soluble FasL, granzyme B and cytochrome c were found in stage
II and stage III of breast cancer patients after chemotherapy compared with
concentrations before chemotherapy (P<0.0001). A significant positive correlation
was found between soluble FasL and cytochrome c as well as between granzyme B and
cytochrome c in breast cancer patients after chemotherapy. CONCLUSION: Serum
concentrations of apoptotic markers such as soluble FasL, granzyme B and
cytochrome c were increased after administration of the first cycle of
chemotherapeutic drugs. The measurement of these circulating apoptotic markers
may help clinicians in evaluating treatment efficacy in breast cancer.
PMID- 25139497
TI - What forgetting tells us about remembering: the influence of top-down control on
hemispheric asymmetries in verbal memory.
AB - It has been suggested that left hemisphere (LH) advantages in verbal processing
is due to superior top-down control of verbal information. It is not clear how
top-down mechanisms affect the encoding and retrieval of verbal information from
hemispheric memory and whether they only influence activation or also encompass
the inhibition of verbal information. The directed forgetting method, in
conjunction with divided visual field presentation, was used to examine the
influence of top-down control mechanisms on hemispheric asymmetries in verbal
memory. Participants were cued to remember or forget words. Cues were presented
either simultaneously with targets or after a short delay. A recognition memory
test using divided visual field presentation was then given. Response times (RTs)
revealed effects of cue timing in the LH. With simultaneous cues, RTs were faster
to "Remember" words compared to "Forget" words. With delayed cues, RTs for
"Remember" and "Forget" words were equivalent. In the right hemisphere (RH),
"Remember" words were consistently faster than "Forget" words, regardless of cue
timing. These data provide evidence that top-down mechanisms influenced LH verbal
memory retrieval more than RH verbal memory retrieval. Finally, there was little
evidence to suggest the hemispheres differ in inhibitory processing.
PMID- 25139498
TI - Unexpected roles for ancient proteins: flavone 8-hydroxylase in sweet basil
trichomes is a Rieske-type, PAO-family oxygenase.
AB - Most elucidated hydroxylations in plant secondary metabolism are catalyzed by
oxoglutarate- or cytochrome P450-dependent oxygenases. Numerous hydroxylations
still evade clarification, suggesting that they might be performed by alternative
enzyme types. Here, we report the identification of the flavone 8-hydroxylase
(F8H) in sweet basil (Ocimum basilicum L.) trichomes as a Rieske-type oxygenase.
Several features of the F8H activity in trichome protein extracts helped to
differentiate it from a cytochrome P450-catalyzed reaction and identify candidate
genes in the basil trichome EST database. The encoded ObF8H proteins share
approximately 50% identity with Rieske-type protochlorophyllide a oxygenases
(PTC52) from higher plants. Homology cloning and DNA blotting revealed the
presence of several PTC52-like genes in the basil genome. The transcripts of the
candidate gene designated ObF8H-1 are strongly enriched in trichomes compared to
whole young leaves, indicating trichome-specific expression. The full-length
ObF8H-1 protein possesses a predicted N-terminal transit peptide, which directs
green fluorescent protein at least in part to chloroplasts. The F8H activity in
crude trichome protein extracts correlates well with the abundance of ObF8H
peptides. The purified recombinant ObF8H-1 displays high affinity for salvigenin
and is inactive with other tested flavones except cirsimaritin, which is 8
hydroxylated with less than 0.2% relative activity. The efficiency of in vivo 8
hydroxylation by engineered yeast was improved by manipulation of protein
subcellular targeting. blast searches showed that occurrence of several PTC52
like genes is rather common in sequenced plant genomes. The discovery of ObF8H
suggests that Rieske-type oxygenases may represent overlooked candidate catalysts
for oxygenations in specialized plant metabolism.
PMID- 25139499
TI - "They Sweat for Science": The Harvard Fatigue Laboratory and Self-Experimentation
in American Exercise Physiology.
AB - In many scientific fields, the practice of self-experimentation waned over the
course of the twentieth century. For exercise physiologists working today,
however, the practice of self-experimentation is alive and well. This paper
considers the role of the Harvard Fatigue Laboratory and its scientific director,
D. Bruce Dill, in legitimizing the practice of self-experimentation in exercise
physiology. Descriptions of self-experimentation are drawn from papers published
by members of the Harvard Fatigue Lab. Attention is paid to the ethical and
practical justifications for self-experimentation in both the lab and the field.
Born out of the practical, immediate demands of fatigue protocols, self
experimentation performed the long-term, epistemological function of uniting
physiological data across time and space, enabling researchers to contribute to a
general human biology program.
PMID- 25139500
TI - Mesenchymal stromal cells as an adjuvant treatment for severe late-onset
hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.
AB - The management of severe late-onset hemorrhagic cystitis (LO-HC) after allogeneic
hematopoietic stem cell transplantation (HSCT) is still challenging. Because
mesenchymal stromal cells (MSCs) possess anti-inflammatory and tissue repair
promoting properties, we retrospectively analyzed the efficacy and safety of MSC
infusions in 7 of 33 patients with severe LO-HC after allogeneic HSCT. During
treatment, each patient received at least one MSC infusion of Wharton's jelly
derived from the umbilical cord of a third-party donor. In 6 patients, MSC
treatment was initiated within 3 days of gross hematuria onset, while the 7th
patient received an infusion 40 days later. The median dose was 1.0 (0.8-1.6) *
10(6)/kg. Five of 7 patients responded to treatment. Notably, gross hematuria
promptly disappeared in 3 patients after 1 infusion, with a time to remission not
seen in patients without MSC infusion. Two patients showed no response even after
several infusions. No acute or late complications were recorded. Our findings
indicate that MSC transfusion might be a feasible and safe supplemental therapy
for patients with severe LO-HC after allogeneic HSCT.
PMID- 25139501
TI - Interventional endoscopy for the treatment of pancreatic pseudocyst and walled
off necrosis (with videos).
AB - Pancreatic pseudocysts and walled-off necrosis are typical late complications of
acute pancreatitis, and they require drainage in symptomatic cases presenting
with infection. Transgastrointestinal endoscopic treatment with endoscopic
ultrasound-guided drainage has become common and yields a good treatment outcome
for pancreatic pseudocyst. Walled-off necrosis, however, contains necrotic
tissue, and thus many cases additionally require an invasive treatment that
includes endoscopic necrosectomy. Methods that involve a procedure-specific large
diameter metal stent, additional endoscopic drainage techniques, and the hybrid
approach method of adding percutaneous drainage have been described, and
considerable advances in these methods have now made it possible to cure almost
all cases of walled-off necrosis with endoscopic treatment alone. However,
without being restricted to endoscopic treatments, a wide range of options
including surgery should be considered as treatments for walled-off necrosis.
PMID- 25139502
TI - A methodological review of the Short Form Health Survey 36 (SF-36) and its
derivatives among breast cancer survivors.
AB - PURPOSE: A systematic review of the validity, reliability and sensitivity of the
Short Form (SF) health survey measures among breast cancer survivors. METHODS: We
searched a number of databases for peer-reviewed papers. The methodological
quality of the papers was assessed using the COnsenus-based Standards for the
selection of health Measurement INstruments (COSMIN). RESULTS: The review
identified seven papers that assessed the psychometric properties of the SF-36 (n
= 5), partial SF-36 (n = 1) and SF-12 (n = 1) among breast cancer survivors.
Internal consistency scores for the SF measures ranged from acceptable to good
across a range of language and ethnic sub-groups. The SF-36 demonstrated good
convergent validity with respective subscales of the Functional Assessment of
Cancer Treatment-General scale and two lymphedema-specific measures. Divergent
validity between the SF-36 and Lymph-ICF was modest. The SF-36 demonstrated good
factor structure in the total breast cancer survivor study samples. However, the
factor structure appeared to differ between specific language and ethnic sub
groups. The SF-36 discriminated between survivors who reported or did not report
symptoms on the Breast Cancer Prevention Trial Symptom Checklist and SF-36
physical sub-scales, but not mental sub-scales, discriminated between survivors
with or without lymphedema. Methodological quality scores varied between and
within papers. CONCLUSION: Short Form measures appear to provide a reliable and
valid indication of general health status among breast cancer survivors though
the limited data suggests that particular caution is required when interpreting
scores provided by non-English language groups. Further research is required to
test the sensitivity or responsiveness of the measure.
PMID- 25139503
TI - Nestin downregulation in rat vascular smooth muscle cells represents an early
marker of vascular disease in experimental type I diabetes.
AB - BACKGROUND: Nestin was reported to directly contribute to cell proliferation and
the intermediate filament protein was detected in vascular smooth muscle cells.
In experimental type I diabetes, nestin downregulation in the heart was
identified as an incipient pathophysiological event. The following study tested
the hypothesis that dysregulation of nestin expression in vascular smooth muscle
cells represented an early event of vascular disease in experimental type I
diabetes. METHODS/RESULTS: In the carotid artery and aorta of adult male Sprague
Dawley rats, a subpopulation of vascular smooth muscle cells co-expressed nestin
and was actively involved in the cell cycle as reflected by the co-staining of
nuclear phosphohistone-3. The infection of aortic vascular smooth muscle cells
with a lentivirus containing a shRNAmir directed against nestin significantly
reduced protein expression and concomitantly attenuated basal DNA synthesis. Two
weeks following injection of adult male Sprague-Dawley rats with streptozotocin,
the endothelial response of aortic rings to acetylcholine, vascular morphology
and the total density of vascular smooth muscle cells in the vasculature of type
I diabetic rats were similar to normal rats. By contrast, nestin protein levels
and the density of nestin(+)/phosphohistone-3(+)-vascular smooth muscle cells
were significantly reduced in type I diabetic rats. The in vivo observations were
recapitulated in vitro as exposure of vascular smooth muscle cells to 30 mM D
glucose inhibited DNA synthesis and concomitantly reduced nestin protein
expression. CONCLUSIONS: Hyperglycaemia-mediated nestin downregulation and the
concomitant reduction of cycling vascular smooth muscle cells represent early
markers of vascular disease in experimental type I diabetes.
PMID- 25139504
TI - Stages of recovery in early psychosis: Associations with symptoms, function, and
narrative development.
AB - OBJECTIVES: This study sought to explore the links between recovery stages,
symptoms, function, and narrative development among individuals with a recent
onset of psychosis. DESIGN: A qualitative longitudinal study was conducted
including quantitative data at baseline. METHODS: Forty-seven participants were
administered the Indiana Psychiatric Illness Interview three times over 9 months
and content analysis was performed. Participants also completed the Social
Functioning Scale, the Brief Psychiatric Rating Scale--Expanded, the California
Verbal Learning Test, and the Trailing Making Test at baseline. Descriptive
discriminant analysis was performed. RESULTS: Results suggested that participants
were mostly in the first two stages of recovery (moratorium, awareness) and that
being in the awareness, rather than moratorium, stage was associated, to a
different extent, with richer narrative development, better levels of
psychosocial function, less negative and positive symptoms, and more years of
education. Furthermore, recovery appeared to be a stable process over the
assessment period. CONCLUSIONS: Recovery is a complex concept including objective
and subjective aspects. In the recovery path of persons recently diagnosed with
psychosis, social engagement, narrative development, and occupational functioning
seem to be particularly important aspects. This study is a first step, and future
research is needed with larger and more diverse participant pools, and
assessments conducted over longer periods of time. PRACTITIONER POINTS: As
greater level of social engagement was the most robust predictor of membership in
the awareness versus moratorium stage, treatment of early psychosis should
include interventions targeting social relations and social skills. As greater
narrative development was the second most robust predictor, enhancing it via
psychotherapy could be a pertinent clinical goal.
PMID- 25139505
TI - Ebola.
PMID- 25139506
TI - Experimental countermeasures against Ebola virus: current progress and an ethical
conundrum.
PMID- 25139513
TI - Wide complex tachycardia: what is the mechanism?
PMID- 25139514
TI - One-year vascular adaptations following pregnancies complicated by hypertension.
PMID- 25139515
TI - Experts condemn "flawed" NICE process over its rejection of prostate cancer drug.
PMID- 25139516
TI - Impact of advanced hearing aid technology on speech understanding for older
listeners with mild to moderate, adult-onset, sensorineural hearing loss.
AB - BACKGROUND: Hearing loss is one of the most common chronic health conditions of
older people. Hearing aids are the customary treatment and they improve quality
of life in older adults. Even so, relatively few older adults with uncomplicated,
mild to moderate, adult-onset, sensorineural hearing loss use hearing aids. One
reason for this is a belief that hearing aids do not provide sufficient value to
justify their expense. Although modern hearing aids are available at several
price points, there is minimal evidence about the relative benefits of premium
level versus basic-level hearing aid technologies. OBJECTIVE: This research was
designed to demonstrate the relative effectiveness of premium hearing aids
compared with basic hearing aids in improving speech understanding and quality of
life. METHODS: 25 participants, including both new and experienced hearing aid
users, completed blinded month-long field trials with each of four pairs of
hearing aids: two basic and two premium level. Outcomes were laboratory speech
understanding tests, standardized questionnaires and open-ended diary items.
RESULTS: Participants reacted very positively to all the hearing aids. Both
everyday speech understanding and quality of life were substantially improved
with hearing aids. RESULTS for both new and experienced users were consistent
with a conclusion that there were no statistically significant or clinically
important differences in improvement between the premium- and basic-level hearing
aids. CONCLUSIONS: It should not be assumed that more costly hearing aids always
produce better outcomes. With contemporary hearing aids from two major
manufacturers, the subjects obtained as much improvement in speech understanding
and quality of life from lower-cost basic-level instruments as from higher-cost
premium-level instruments. Regardless of technology level, comprehensive best
practice fitting protocols should be followed to optimize results for every
patient.
PMID- 25139517
TI - Preclinical evaluation and test-retest studies of [(18)F]PSS232, a novel
radioligand for targeting metabotropic glutamate receptor 5 (mGlu5).
AB - PURPOSE: A novel, (18)F-labelled metabotropic glutamate receptor subtype 5
(mGlu5) derivative of [(11)C]ABP688 ([(11)C]1), [(18)F]PSS232 ([(18)F] ]5), was
evaluated in vitro and in vivo for its potential as a PET agent and was used in
test-retest reliability studies METHODS: The radiosynthesis of [(18)F]5 was
accomplished via a one-step reaction using a mesylate precursor. In vitro
stability was determined in PBS and plasma, and with liver microsomal enzymes.
Metabolite studies were performed using rat brain extracts, blood and urine. In
vitro autoradiography was performed on horizontal slices of rat brain using 1 and
8, antagonists for mGlu5 and mGlu1, respectively. Small-animal PET,
biodistribution, and test-retest studies were performed in Wistar rats. In vivo,
dose-dependent displacement studies were performed using 6 and blocking studies
with 7. RESULTS: [(18)F]5 was obtained in decay-corrected maximal radiochemical
yield of 37 % with a specific activity of 80 - 400 GBq/MUmol. Treatment with rat
and human microsomal enzymes in vitro for 60 min resulted in 20 % and 4 % of
hydrophilic radiometabolites, respectively. No hydrophilic decomposition products
or radiometabolites were found in PBS or plasma. In vitro autoradiography on rat
brain slices showed a heterogeneous distribution consistent with the known
distribution of mGlu5 with high binding to hippocampal and cortical regions, and
negligible radioactivity in the cerebellum. Similar distribution of radioactivity
was found in PET images. Under displacement conditions with 6, reduced [(18)F]5
binding was found in all brain regions except the cerebellum. 7 reduced binding
in the striatum by 84 % on average. Test-retest studies were reproducible with a
variability ranging from 6.8 % to 8.2 %. An extended single-dose toxicity study
in Wistar rats showed no compound-related adverse effects. CONCLUSION: The new
mGlu5 radiotracer, [(18)F]5, showed specific and selective in vitro and in vivo
properties and is a promising radioligand for PET imaging of mGlu5 in humans.
PMID- 25139518
TI - Incidental colonic focal FDG uptake on PET/CT: can the maximum standardized
uptake value (SUVmax) guide us in the timing of colonoscopy?
AB - PURPOSE: In patients undergoing (18)F-FDG PET/CT, incidental colonic focal
lesions can be indicative of inflammatory, premalignant or malignant lesions. The
maximum standardized uptake value (SUVmax) of these lesions, representing the FDG
uptake intensity, might be helpful in differentiating malignant from benign
lesions, and thereby be helpful in determining the urgency of colonoscopy. The
aim of our study was to assess the incidence and underlying pathology of
incidental PET-positive colonic lesions in a large cohort of patients, and to
determine the usefulness of the SUVmax in differentiating benign from malignant
pathology. METHODS: The electronic records of all patients who underwent FDG
PET/CT from January 2010 to March 2013 in our hospital were retrospectively
reviewed. The main indications for PET/CT were: characterization of an
indeterminate mass on radiological imaging, suspicion or staging of malignancy,
and suspicion of inflammation. In patients with incidental focal FDG uptake in
the large bowel, data regarding subsequent colonoscopy were retrieved, if
performed within 120 days. The final diagnosis was defined using colonoscopy
findings, combined with additional histopathological assessment of the lesion, if
applicable. RESULTS: Of 7,318 patients analysed, 359 (5 %) had 404 foci of
unexpected colonic FDG uptake. In 242 of these 404 lesions (60 %), colonoscopy
follow-up data were available. Final diagnoses were: adenocarcinoma in 25 (10 %),
adenoma in 90 (37 %), and benign in 127 (53 %). The median [IQR] SUVmax was
significantly higher in adenocarcinoma (16.6 [12 - 20.8]) than in benign lesions
(8.2 [5.9 - 10.1]; p < 0.0001), non-advanced adenoma (8.3 [6.1 - 10.5]; p <
0.0001) and advanced adenoma (9.7 [7.2 - 12.6]; p < 0.001). The receiver
operating characteristic curve of SUVmax for malignant versus nonmalignant
lesions had an area under the curve of 0.868 (SD +/- 0.038), the optimal cut-off
value being 11.4 (sensitivity 80 %, specificity 82 %, positive predictive value
34 %, negative predictive value 98 %). CONCLUSION: In these patients with
incidental colonic focal activity undergoing PET/CT (the largest series published
to date), malignancies had significantly higher SUVmax values than all other
types of lesions. However, SUVmax could not distinguish between benign lesions
and adenomas. In conclusion, all incidental findings in the colon should be
further evaluated and lesions with SUVmax >=11.4 should be evaluated without
delay.
PMID- 25139519
TI - Diagnostic and therapeutic uses of nanomaterials in the brain.
AB - Nanomedicine has recently emerged as an exciting tool able to improve the early
diagnosis and treatment of a variety of intractable or age-related brain
disorders. The most relevant properties of nanomaterials are that they can be
engineered to cross the blood brain barrier, to target specific cells and
molecules and to act as vehicles for drugs. Potentially beneficial properties of
nanotherapeutics derived from its unique characteristics include improved
efficacy, safety, sensitivity and personalization compared to conventional
medicines. In this review, recent advances in available nanostructures and
nanomaterials for brain applications will be described. Then, the latest
applications of nanotechnology for the diagnosis and treatment of neurological
disorders, in particular brain tumors and neurodegenerative diseases, will be
reviewed. Recent investigations of the neurotoxicity of the nanomaterial both in
vitro and in vivo will be summarized. Finally, the ongoing challenges that have
to be meet if new nanomedical products are to be put on the market will be
discussed and some future directions will be outlined.
PMID- 25139520
TI - Ischemic colitis: A forgotten entity. Results of a retrospective study in 118
patients.
AB - OBJECTIVE: The aim of our study was to document our 6-year experiences in
identifying the clinical characteristics, laboratory findings, risk factors and
the outcomes of patients with ischemic colitis (IC) in a community hospital
setting. METHODS: The medical records of patients who were diagnosed with IC from
2007 to 2013 in two community hospitals were retrospectively reviewed. Their
clinical characteristics, laboratory results, radiological, endoscopic and
histological evidence, anatomic location of the lesion, comorbidities,
concomitant use of drugs, and so on, were collected. RESULTS: A total of 118
patients with IC was identified, most were elderly individuals with a female
predominance. The most common symptoms were abdominal pain, rectal bleeding and
diarrhea. Hypertension, hyperlipidemia, coronary artery disease and diabetes
mellitus were the most common comorbidities. Erythema, edema and
erosions/ulcerations were the most common endoscopic findings. Left colon was the
most affected location of lesion (84.8%), and there was one case of pancolitis.
The descending colon was the most common affected segment, while rectum was the
least affected segment. Severe IC occurred in 12.7% of the patients. Death within
30 days from the diagnosis of the disease occurred in 4.2%. CONCLUSIONS: IC is
majorly occurred in elderly with a female predominance. Cardiovascular disease
and its associated risk factors are the most common comorbidities. Left colon is
the most affected location of the disease and the overall mortality rate was
4.2%. Physicians should make every effort to identify these patients, especially
those with high risks.
PMID- 25139521
TI - Memory traces of long-range coordinated oscillations in the sleeping human brain.
AB - Cognition involves coordinated activity across distributed neuronal networks.
Neuronal activity during learning triggers cortical plasticity that allows for
reorganization of the neuronal network and integration of new information. Animal
studies have shown post-learning reactivation of learning-elicited neuronal
network activity during subsequent sleep, supporting consolidation of the
reorganization. However, no previous studies, to our knowledge, have demonstrated
reactivation of specific learning-elicited long-range functional connectivity
during sleep in humans. We here show reactivation of learning-induced long-range
synchronization of magnetoencephalography power fluctuations in human sleep.
Visuomotor learning elicited a specific profile of long-range cortico-cortical
synchronization of slow (0.1 Hz) fluctuations in beta band (12-30 Hz) power. The
parieto-occipital part of this synchronization profile reappeared in delta band
(1-3.5 Hz) power fluctuations during subsequent sleep, but not during the
intervening wakefulness period. Individual differences in the reactivated
synchronization predicted postsleep performance improvement. The presleep resting
state synchronization profile was not reactivated during sleep. The findings
demonstrate reactivation of long-range coordination of neuronal activity in
humans, more specifically of reactivation of coupling of infra-slow fluctuations
in oscillatory power. The spatiotemporal profile of delta power fluctuations
during sleep may subserve memory consolidation by echoing coordinated activation
elicited by prior learning.
PMID- 25139522
TI - Renal denervation for treatment of hypertension and beyond.
PMID- 25139523
TI - Blood pressure and blood flow find its way.
PMID- 25139525
TI - Reconfigurable swarms of nematic colloids controlled by photoactivated surface
patterns.
AB - Different phoretic driving mechanisms have been proposed for the transport of
solid or liquid microscopic inclusions in integrated chemical processes. It is
now shown that a substrate that was chemically modified with photosensitive self
assembled monolayers enables the direct control of the assembly and transport of
large ensembles of micrometer-sized particles and drops that were dispersed in a
thin layer of anisotropic fluid. This strategy separates particle driving, which
was realized by AC electrophoresis, and steering, which was achieved by elastic
modulation of the nematic host fluid. Inclusions respond individually or in
collective modes following arbitrary reconfigurable paths that were imprinted by
irradiation with UV or blue light. Relying solely on generic material properties,
the proposed procedure is versatile enough for the development of applications
that involve either inanimate or living materials.
PMID- 25139524
TI - A spatial simulation model for dengue virus infection in urban areas.
AB - BACKGROUND: The World Health Organization estimates that the global number of
dengue infections range between 80-100 million per year, with some studies
estimating approximately three times higher numbers. Furthermore, the geographic
range of dengue virus transmission is extending with the disease now occurring
more frequently in areas such as southern Europe. Ae. aegypti, one of the most
prominent dengue vectors, is endemic to the far north-east of Australia and the
city of Cairns frequently experiences dengue outbreaks which sometimes lead to
large epidemics. METHOD: A spatially-explicit, individual-based mathematical
model that accounts for the spread of dengue infection as a result of human
movement and mosquito dispersion is presented. The model closely couples the four
key sub-models necessary for representing the overall dynamics of the physical
system, namely those describing mosquito population dynamics, human movement,
virus transmission and vector control. Important features are the use of high
quality outbreak data and mosquito trapping data for calibration and validation
and a strategy to derive local mosquito abundance based on vegetation coverage
and census data. RESULTS: The model has been calibrated using detailed 2003
dengue outbreak data from Cairns, together with census and mosquito trapping
data, and is shown to realistically reproduce a further dengue outbreak. The
simulation results replicating the 2008/2009 Cairns epidemic support several
hypotheses (formulated previously) aimed at explaining the large-scale epidemic
which occurred in 2008/2009; specifically, while warmer weather and increased
human movement had only a small effect on the spread of the virus, a shorter
virus strain-specific extrinsic incubation time can explain the observed
explosive outbreak of 2008/2009. CONCLUSION: The proof-of-concept simulation
model described in this study has potential as a tool for understanding factors
contributing to dengue spread as well as planning and optimizing dengue control,
including reducing the Ae. aegypti vector population and for estimating the
effectiveness and cost-effectiveness of future vaccination programmes. This model
could also be applied to other vector borne viral diseases such as chikungunya,
also spread by Ae. aegypti and, by re-parameterisation of the vector sub-model,
to dengue and chikungunya viruses spread by Aedes albopictus.
PMID- 25139526
TI - Head-mounted display for a personal integrated image monitoring system: ureteral
stent placement.
AB - The personal head-mounted display (HMD) has emerged as a novel image monitoring
system. We present here the application of a high-definition organic
electroluminescent binocular HMD in ureteral stent placement. Our HMD system
displayed multiple forms of information such as integrated, sharp, high-contrast
images using a four-split screen or a picture-in-picture technique both
seamlessly and synchronously. When both the operator and the assistant wore an
HMD, they could continuously and simultaneously monitor the cystoscopic and
fluoroscopic images in an ergonomically natural position. Furthermore, each
participant was able to modulate the displayed images depending on the procedure.
In all five cases, both the operator and the assistant successfully used this
system with no unfavorable event. No participants experienced any HMD wear
related adverse effects. We therefore believe this HMD system might be
potentially beneficial during ureteral stent placement procedures. Furthermore,
it is compact, easily introduced and affordable.
PMID- 25139527
TI - 7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cell
death through modulating PI3K/Akt and JNK pathways.
AB - We have recently shown that 7,8-dihydroxyflavone (7,8-DHF) protects PC12 cells
against 6-OHDA-induced cytotoxicity through its antioxidant activity. In the
present study, we investigated the molecular mechanisms underlying the neuronal
protective activity of 7,8-DHF. Western blot analysis showed that 6-OHDA (100MUM,
24h) enhanced the phosphorylation of JNK and ERK1/2, but it markedly suppressed
the expression of p-Akt, implying that 6-OHDA induces PC12 cell death through
activating the pro-apoptotic MAPKs pathway but suppressing the survival PI3K/Akt
pathway. More importantly, addition of 7,8-DHF fully prevented the activation of
JNK and suppression of Akt induced by 6-OHDA. Interestingly, pretreatment with
the PI3K-specific inhibitor LY294002 largely blocked 7,8-DHF function in
protecting PC12 cells from 6-OHDA-induced cell death. In contrast, the MEK
inhibitor PD98059 showed little effect on the protective activity of 7,8-DHF.
These results suggest that 7,8-DHF might protect PC12 cells from 6-OHDA-induced
cell death through activating PI3K/Akt pathway and inhibiting JNK pathway.
PMID- 25139528
TI - Disruption reduces accuracy and P3b amplitudes in the attentional blink.
AB - In everyday life, distracting stimuli often interfere with daily tasks, and
disrupt successful task performance. The attentional blink paradigm (a deficit in
reporting the second target (T2) in a rapid stream of visual stimuli) allows for
an investigation of disruption by rapidly appearing stimuli. Specifically, the
magnitude of the attentional blink deficit can be manipulated by positioning
relevant stimuli at strategic locations within the visual stream. The current
study therefore designed and tested a disruption paradigm that aimed to reduce T2
accuracy using a disruptor stimulus. Electroencephalography was used to reveal
the neural correlates of the effect. To that end, targets were defined by task
set colours. The item immediately preceding T2 appeared in a task-set colour
(disrupted trials) or a different colour (non-disrupted trials). The results
revealed that T2 accuracy was reduced on disrupted trials, and disruption
appeared to be worse when T2 appeared inside the attentional blink window. The
behavioural data were paralleled by the neural results. On trials where T2
appeared within the AB window and was correctly reported, T2-P3b amplitude (a
neural correlate of working memory consolidation) was significantly depressed on
disrupted trials compared with non-disrupted trials. Single trial plots of P3b
amplitude confirmed a weaker neural trace for T2 on disrupted trials. These data
indicate that the magnitude and neural signature of the attentional blink deficit
is malleable, and can be influenced by non-target, task-relevant stimuli.
PMID- 25139529
TI - rs11098403 polymorphism near NDST3 is associated with a reduced risk of
schizophrenia in a Han Chinese population.
AB - A recent genome-wide association study indicated that rs11098403, a single
nucleotide polymorphism in the vicinity of NDST3, was strongly associated with
the risk of schizophrenia in Caucasians. However, this relation has not been
validated in other populations or ethnic groups. Herein, we conducted a case
control study to investigate the association of rs11098403 polymorphism with the
schizophrenia risk in a Han Chinese population comprising 440 schizophrenia
patients and 450 control subjects. For the first time, we showed that the minor
allele (G) of rs11098403 is closely associated with a reduced risk of
schizophrenia (OR=0.614; 95% CI: 0.453-0.833; P=0.002; Power=0.832). Meanwhile,
the G allele of rs11098403 seemed to reduce the schizophrenia risk via a dominant
manner (GG+AG vs. AA, OR=0.526; 95% CI: 0.374-0.74; P<0.001). Furthermore, this
association was further confirmed using an independent replication sample
containing 267 schizophrenia patients and 400 control subjects with a Han Chinese
descent (OR=0.652; 95% CI: 0.469-0.907; P=0.011; Power=0.772). Taken together,
these findings demonstrate a significant association between rs11098403 and
schizophrenia risk in Han Chinese, confirming the data that previously obtained
from Caucasians.
PMID- 25139530
TI - XLPE based Al2O3-clay binary and ternary hybrid nanocomposites: self-assembly of
nanoscale hybrid fillers, polymer chain confinement and transport
characteristics.
AB - Transport properties of hybrid nanoparticle based cross-linked polyethylene
(XLPE)-Al2O3-clay binary and ternary nanocomposites have been investigated with
special significance to the hybrid effect and synergism of hybrid nanofillers.
Compiling the temperature and filler effects demonstrates the self-assembly of
hybrid nanofillers in confining the polymer chain dynamics. Studies on transport
mechanisms, transport coefficients, and swelling parameters confirm the superior
solvent resistant properties of hybrid filler reinforced nanocomposites.
Experiments confirmed the extra stability of the ternary hybrid nanocomposites
against the process of solvent penetration. Thermodynamic and kinetic
investigations reveal that the nanofillers are competent to alter the
thermodynamic feasibility and rate constant parameters. Theoretical predictions
by the Peppas-Sahlin model suggest that the diffusion process is well thought-out
to be a combination of diffusion into the swollen polymer and the polymer chain
relaxation process. The morphology and the network density estimation confirm the
presence of filler networks and the trapped polymer chains inside them, in
ternary systems, which elucidate the microstructure assisted solvent resistant
properties of the ternary hybrid nanocomposites. The amount of polymer chains
immobilized by the filler surface was computed from dynamic mechanical analysis
and a nice correlation was established between transport characteristics and the
polymer chain confinement.
PMID- 25139531
TI - Range expansion of Ixodes ricinus to higher altitude, and co-infestation of small
rodents with Dermacentor marginatus in the Northern Apennines, Italy.
AB - Immature ticks (Ixodes ricinus and Dermacentor marginatus) were collected from
small rodents (Apodemus spp. and Myodes glareolus), in the Northern Apennines,
Italy, at an altitude up to 1650 m above sea level (a.s.l.), from 2009 through
2012. While D. marginatus had been found at the same location in studies carried
out in 1994, I. ricinus was very rare or absent. Prevalence (95% confidence
interval) of infestation by I. ricinus larvae on Apodemus spp. was 54.4% (47.5,
61.2), and it was greater than prevalence of D. marginatus larvae on the same
hosts (23.3%, 17.8, 29.5). The mean (standard deviation) numbers of I. ricinus
and D. marginatus larvae per individual Apodemus spp. were similar: 2.3 (4.1) and
2.1 (9.8), respectively. The monthly infestation pattern of the two tick species
on Apodemus spp. were different. I. ricinus larvae were more frequent in June and
September, than in July-August. I. ricinus nymphs were generally rare, and were
most frequently found in July. The prevalence of D. marginatus larvae peaked in
July-August, whereas nymphs were mostly active in August-September. Increasing
population densities of roe deer (Capreolus capreolus), and increasing
temperatures, in the last decades, in the Apennine area might have contributed to
the observed range expansion of I. ricinus.
PMID- 25139532
TI - Preoperative chemoradiation therapy for esophageal cancer is a risk factor for
the elevation of high mobility group box-1, leading to an increase in
postoperative severe pulmonary complications.
AB - We herein clarified the time course of changes in the serum high mobility group
box chromosomal protein-1 (HMGB-1) concentrations in esophageal cancer patients
after esophagectomy, and investigated whether the perioperative serum HMGB-1
levels correlate with the administration of neoadjuvant chemoradiation therapy
(NACRT) and the postoperative clinical course, especially the occurrence of
pulmonary complications, in such patients. Sixty patients who underwent right
transthoracic esophagectomy for esophageal cancer were enrolled in this study.
The relationship between the perioperative serum HMGB-1 levels and NACRT, and the
postoperative severe pulmonary complications were evaluated. Patients with severe
pulmonary complications (n = 44) tended to have undergone NACRT more often than
those without severe pulmonary complications (n = 16). The preoperative and
postoperative day 7 serum HMGB-1 concentrations were significantly higher in
patients with severe pulmonary complications than those in patients without
severe pulmonary complications. In the univariate and multivariate analyses, the
use of NACRT and the preoperative elevations in the serum HMGB-1 levels (>4.2
ng/mL) were found to be significantly associated with pulmonary dysfunction.
Furthermore, the response to NACRT was found to be significantly associated with
the preoperative serum HMGB-1 levels. The use of NACRT contributes to
preoperative serum HMGB-1 elevation, and these were risk factors for the
occurrence of severe postoperative pulmonary complications in patients with
esophageal cancer after thoracic esophagectomy.
PMID- 25139533
TI - Increased oligodendrogenesis by humanin promotes axonal remyelination and
neurological recovery in hypoxic/ischemic brains.
AB - Oligodendrocytes are the predominant cell type in white matter and are highly
vulnerable to ischemic injury. The role of oligodendrocyte dysfunction in
ischemic brain injury is unknown. In this study, we used a 24-amino acid peptide
S14G-Humanin (HNG) to examine oligodendrogenesis and neurological functional
recovery in a hypoxic/ischemic (H/I) neonatal model. Intraperitoneal HNG pre
treatment decreased infarct volume following H/I injury. Delayed HNG treatment 24
h after H/I injury did not reduce infarct volume but did decrease neurological
deficits and brain atrophy. Delayed HNG treatment did not attenuate axonal
demyelination at 48 h after H/I injury. However, at 14 d after H/I injury,
delayed HNG treatment increased axonal remyelination, the thickness of corpus
callosum at the midline, the number of Olig2(+) /BrdU(+) cells, and levels of
brain-derived neurotrophic factor (BDNF). Our results suggest that targeting
oligodendrogenesis via delayed HNG treatment may represent a promising approach
for the treatment of stroke.
PMID- 25139534
TI - Molecular features and survival outcomes of the intrinsic subtypes within HER2
positive breast cancer.
AB - BACKGROUND: The clinical impact of the biological heterogeneity within HER2
positive (HER2+) breast cancer is not fully understood. Here, we evaluated the
molecular features and survival outcomes of the intrinsic subtypes within HER2+
breast cancer. METHODS: We interrogated The Cancer Genome Atlas (n = 495) and
Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets
(n = 1730) of primary breast cancers for molecular data derived from DNA, RNA and
protein, and determined intrinsic subtype. Clinical HER2 status was defined
according to American Society of Clinical Oncology (ASCO)/College of American
Pathologists (CAP) guidelines or DNA copy-number aberration by single nucleotide
polymorphism arrays. Cox models tested the prognostic significance of each
variable in patients not treated with trastuzumab (n = 1711). RESULTS: Compared
with clinically HER2 (cHER2)-negative breast cancer, cHER2+ breast cancer had a
higher frequency of the HER2-enriched (HER2E) subtype (47.0% vs 7.1%) and a lower
frequency of Luminal A (10.7% vs 39.0%) and Basal-like (14.1% vs 23.4%) subtypes.
The likelihood of cHER2-positivity in HER2E, Luminal B, Basal-like and Luminal A
subtypes was 64.6%, 20.0%, 14.4% and 7.3%, respectively. Within each subtype,
only 0.3% to 3.9% of genes were found differentially expressed between cHER2+ and
cHER2-negative tumors. Within cHER2+ tumors, HER2 gene and protein expression was
statistically significantly higher in the HER2E and Basal-like subtypes than
either luminal subtype. Neither cHER2 status nor the new 10-subtype copy number
based classification system (IntClust) added independent prognostic value to
intrinsic subtype. CONCLUSIONS: When the intrinsic subtypes are taken into
account, cHER2-positivity does not translate into large changes in the expression
of downstream signaling pathways, nor does it affect patient survival in the
absence of HER2 targeting.
PMID- 25139535
TI - HER2-positive breast cancer, intrinsic subtypes, and tailoring therapy.
PMID- 25139536
TI - Commentary: Socioeconomic status and hypertension in low- and middle-income
countries: can we learn anything from existing studies?
PMID- 25139537
TI - Rejoinder: Socioeconomic gradients and hypertension in low- and middle-income
countries: a straw man and no solutions.
PMID- 25139538
TI - Comparison of Chinese and international psychiatrists' views on classification of
mental disorders.
AB - INTRODUCTION: This study aimed to explore the views and attitudes of Chinese
psychiatrists on mental disorders classification, and to compare their
similarities and differences with those of the international mental health
professionals. METHODS: Two hundred and ninety members of the Chinese Society of
Psychiatry were invited to participate in the study and 211 completed the survey.
RESULTS: Ninety-one percent of Chinese participants regularly used a formal
classification system, with more users of the International Classification of
Diseases 10th Revision (ICD-10; 48.8%) or Chinese Classification of Mental
Disorders 3rd Edition (39.3%) than the 4th Edition of Diagnostic and Statistical
Manual (11.4%). Like their global counterparts, Chinese respondents regarded
communication among clinicians as the most important purpose of a classification
and preferred a simpler system with fewer categories. Chinese psychiatrists were
more likely than international participants to prefer a system with strict
diagnostic criteria for all disorders and to endorse problems with a cultural
applicability of the classification. However, only a minority (31.3%) indicated
that they saw a need for a national classification. DISCUSSION: Overall, Chinese
psychiatrists have similar opinions and attitudes on most issues of the
classification to the international clinicians. Areas of divergent views may
provide meaningful information for ICD revision in China.
PMID- 25139539
TI - Investigating the role of neuropathic pain relief in decreasing gait variability
in diabetes mellitus patients with neuropathic pain: a randomized, double-blind
crossover trial.
AB - BACKGROUND: Subjects with diabetes mellitus (DM) develop gait dysfunction
contributing to falls, reluctance to perform activities and injuries. Neuropathic
pain (NeP) related to diabetic peripheral neuropathy (DPN) is associated with
increased gait variability that may contribute to gait dysfunction. We used a
portable device (GaitMeterTM) and related gait and balance measures to measure
gait parameters in painful DPN (PDPN) subjects prior to and during analgesia. Our
hypothesis was that PDPN subjects would have decreased gait step variability when
receiving pharmacological relief of NeP. METHODS: DPN subjects with at least
moderate NeP were assessed in a randomized, double-blind crossover study of
pregabalin versus placebo. The outcome measure was variability in step length and
step velocity. Testing for Timed Get-Up-and-Go Test, Tinetti Mobility Scales,
Sway Testing, a Physiological Profile Approach, and fall-related surveys were
also performed. DPN severity was quantified using the Utah Early Neuropathy
Score. RESULTS: PDPN subjects developed increased, rather than decreased, step
length and step velocity variability during pregabalin treatment. There were no
significant differences between cohorts for other physiological gait and balance
testing. Non-significant NeP relief occurred in the pregabalin phase of study as
compared with placebo. There was a negative relationship for step length with
pain severity. CONCLUSION: Analgesia did not decrease gait variability in PDPN
patients, and in fact, increased gait variability was seen during pregabalin
treatment. Other important relationships of gait dysfunction with PDPN should be
sought.
PMID- 25139540
TI - Routine plasma biochemistry analytes in clinically healthy cats: within-day
variations and effects of a standard meal.
AB - Limited information is available on pre-analytical variations in plasma analytes
in cats. The objectives of this study were to assess the effects of the time of
sampling and a standard meal on plasma analytes in healthy cats. Eight healthy,
adult, fasted cats underwent blood sampling every 2 h from 8 am to 8 pm twice at
a 12 day interval. On the days of sampling, four cats were kept fasted and the
others were fed just after the first sample, in a crossover design. Plasma
glucose, urea, creatinine, sodium, potassium, chloride, CO2, calcium, phosphate,
proteins, albumin, cholesterol and triglycerides, alanine aminotransferase and
alkaline phosphatase were assayed on each sample. Effects of time of sampling and
meal on plasma biochemistry results were tested using a general linear model.
Diurnal variations in tested plasma analytes in fasted cats were negligible
except for urea and creatinine, which gave noticeably higher plasma
concentrations in the afternoon than in the morning. Observed postprandial
variations were of some importance for phosphate and creatinine and of
indisputable clinical relevance for CO2 and urea.
PMID- 25139542
TI - Cosmetic surgeon is struck off for putting commercial interests ahead of his
patients.
PMID- 25139543
TI - Selective transamidation of 3-oxo-N-acyl homoserine lactones by hydrazine
derivatives.
AB - A method for the selective transamidation of the 3-oxo sub-family of N-acyl
homoserine lactones (3-oxo-AHLs) under physiologically relevant conditions has
been developed. The reaction has the potential to serve as a strategy for
selective knockdown of key autoinducers in a multicellular environment.
PMID- 25139544
TI - Chondroitin sulfate glycosaminoglycans for CNS homeostasis-implications for
material design.
AB - Chondroitin sulfate proteoglycans (CSPGs) are complex biomolecules that are known
to facilitate patterning of axonal direction and cell migration during the early
growth and development phase of the mammalian central nervous system (CNS). In
adults, they continue to control neuronal plasticity as major constituents of the
"peri-neuronal nets" (PNNs) that surround adult CNS neurons. CSPGs are also
barrier-forming molecules that are selectively upregulated by invading reactive
astroglia after injury to the CNS, and are responsible for the active repulsion
of regenerating neurons post-injury. Recent evidence however suggests that the
diverse sulfated glycosaminoglycan (GAG) side chains attached to CSPGs are key
components that play paradoxical roles in influencing nerve regeneration post
injury to the CNS. Sulfated GAG repeats attached to the CSPG core protein help
mediate cell migration, neuritogenesis, axonal pathfinding, and axonal repulsion
by directly trapping and presenting a whole host of growth factors to cells
locally, or by binding to specific membrane bound proteins on the cell surface to
influence cellular function. In this review, we will present the current gamut of
interventional strategies used to bridge CNS deficits, and discuss the potential
advantages of using sulfated GAG based biomaterials to facilitate the repair and
regeneration of the injured CNS.
PMID- 25139545
TI - Mutations in the NS5A gene of hepatitis C virus subtype 1b and response to peg
IFNalpha-2a/RBV combination therapy in Azerbaijani patients.
AB - Hepatitis C virus (HCV) infection is one of the major causes of chronic liver
disease throughout the world. The presence of mutations in different regions of
the HCV subtype 1b (HCV-1b) nonstructural 5A (NS5A) gene may be associated with
response to interferon therapy. This study evaluated whether amino acid
substitutions in the NS5A protein of HCV-1b correlated with response to pegylated
interferon alfa-2a (peg-IFNalpha-2a) and ribavirin (RBV) combination therapy in
Azerbaijani patients. From March 2010 to April 2014, a total of 34 chronically
HCV-1b-infected Azerbaijani patients were enrolled in this prospective study.
After extraction of RNA from plasma specimens, the entire sequences of the NS5A
gene of HCV was amplified by reverse transcription nested polymerase chain
reaction (RT-nested PCR), and the PCR products were sequenced subsequently. The
data that were obtained revealed that there was no correlation between the
response to HCV combination therapy and the number of mutations in the NS5A
PKRBD, NS5A-ISDR, and NS5A-V3 regions of HCV. It also was found that changes from
isoleucine to valine (I2252 V), aspartic acid to glutamic acid (D2257), arginine
to lysine (R2269 K), and arginine to glycine in NS5A-PKRBD and from glycine to
glutamic acid (G2379E) in the NS5A-V3 region were not associated with HCV
treatment outcome. This study showed that genetic variability in the NS5A-PKRBD,
NS5A-ISDR, and NS5A-V3 regions is not a predictive factor of SVR, NR or relapse
in HCV genotype1b treated with peg-IFNalpha-2a/RBV combination therapy.
PMID- 25139546
TI - Replication of Chinese sacbrood virus in primary cell cultures of Asian honeybee
(Apis cerana).
AB - A primary cell culture system was established for the first time from embryonic
tissues of Asian honeybee, Apis cerana, and used to trace the early infection
process of Chinese sacbrood virus (CSBV), an iflavirus in the family Iflaviridae.
A monolayer of epithelium-like cells of A. cerana, approximately 8-10 MUm in
diameter, was grown in Kimura's insect medium at 28 degrees C within 3-4 days of
setting up the cultures. Such cultured cells were inoculated with CSBV purified
from infected larvae or pupae for 2 h. In electron and confocal micrographs,
viral particles accumulated as filamentous or vesicular inclusions in the
cytoplasm of infected cultured cells at 36 h post-inoculation (hpi). Real-time
quantitative RT-PCR assay showed that the expression levels of four cistrons of
CSBV in the cultured cells increased rapidly between 12 and 48 hpi. This newly
established primary cell culture derived from A. cerana will be useful for
further studies of infection caused by CSBV.
PMID- 25139547
TI - Experimental inoculation of equine coronavirus into Japanese draft horses.
AB - Recently, outbreaks associated with equine coronavirus (ECoV) have occurred in
Japan and the United States. While ECoV is likely to be pathogenic to horses, it
has not been shown that experimental inoculation of horses with ECoV produces
clinical signs of disease. In this study, we inoculated three Japanese draft
horses with an ECoV-positive diarrheic fecal sample to confirm infection after
inoculation and to investigate the clinical course and virus shedding patterns of
ECoV. Virus neutralization tests showed that all three horses became infected
with ECoV. Two of the three horses developed clinical signs similar to those
observed during ECoV outbreaks, including fever, anorexia, and gastrointestinal
dysfunction. All horses excreted a large amount of virus into their feces for
more than 9 days after inoculation regardless of the presence or absence of
clinical signs, which suggests that feces are an important source of ECoV
infection. ECoV was also detected in nasal swabs from all horses, suggesting that
respiratory transmission of ECoV may occur. Both symptomatic horses developed
viremia, while the asymptomatic horse did not. White blood cell counts and serum
amyloid A concentrations changed relative to the clinical condition of the
inoculated horses; these may be useful markers for monitoring the clinical status
of horses infected with ECoV. This is the first report of induction of clinical
signs of ECoV infection in horses by experimental inoculation. These clinical and
virological findings should aid further investigation of the pathogenesis of
ECoV.
PMID- 25139548
TI - Is postoperative computed tomography evaluation a prognostic indicator in
patients with optimally debulked advanced ovarian cancer?
AB - OBJECTIVE: To compare the surgeon's intraoperative assessment of residual tumor
(RT) disease with that identified on postoperative computed tomography (CT) in
patients undergoing optimal primary surgical cytoreduction (RT <1 cm) and to
identify the prognostic significance of postoperative CT scan of RT. METHODS:
Patients with FIGO stage III-IV ovarian cancer treated at the Gynecologic
Oncology Unit of the National Cancer Institute between November 2011 and March
2013, who underwent optimal primary cytoreduction and were entered in prospective
controlled clinical trials requiring a baseline postoperative CT evaluation
within 30 days, were enrolled. All CT scans were reviewed by a dedicated
radiologist to evaluate RT. Median follow-up was 16 months. RESULTS: 64 out of
160 patients met the eligibility criteria. RT = 0, 0.1 < RT < 0.5 cm, and 0.6 <
RT < 1 cm was reported in 53 (82.8%), 9 (14.1%) and 2 (3.1%) cases, respectively.
Postoperative CT disagreed with RT in 13 out of 64 (20.3%) cases. Progression
free survival (PFS) of patients with a positive and negative postoperative CT
scan of RT was 5 months (95% CI 1-15 months) and 28 months (95% CI 2-46 months),
respectively (p < 0.0001). Evidence of the disease using postoperative CT was an
independent prognostic factor in multivariate analysis (HR = 8.87, 95% CI = 3.23
24.31, p < 0.0001). CONCLUSIONS: Evidence of the disease using postoperative CT
was associated with a significant decrease in PFS in patients who underwent
optimal primary cytoreduction. RT status as evaluated with early postoperative CT
may have an important role in prognostic assessment.
PMID- 25139549
TI - Reply to the letter to the editor 'second-line chemotherapy in advanced biliary
cancer: the present now will later be past' by Vivaldi et al.
PMID- 25139550
TI - A phase II randomized study evaluating the addition of iniparib to gemcitabine
plus cisplatin as first-line therapy for metastatic non-small-cell lung cancer.
AB - BACKGROUND: Iniparib is a novel anticancer agent initially considered a poly (ADP
ribose) polymerase (PARP) inhibitor, but subsequently shown to act via non
selective protein modification through cysteine adducts. This randomized phase II
study investigated the addition of iniparib to gemcitabine-cisplatin in
metastatic non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS:
Patients with histologically confirmed stage IV NSCLC were randomized 2 : 1 to
receive gemcitabine (1250 mg/m(2), days 1/8) and cisplatin (75 mg/m(2), day 1)
with [gemcitabine/cisplatin/iniparib (GCI)] or without [gemcitabine/cisplatin
(GC)] iniparib (5.6 mg/kg, days 1/4/8/11) every 3 weeks for six cycles. The
primary end point was the overall response rate (ORR). Secondary objectives
included progression-free survival (PFS), overall survival (OS), and safety. The
study was not designed for formal efficacy comparison, the control arm being to
benchmark results against the literature. RESULTS: One hundred and nineteen
patients were randomized (39 GC and 80 GCI). More GCI patients were male (80% GCI
and 67% GC) and had PS 0 (61% GCI and 49% GC). The ORR was 25.6% [95% confidence
interval (CI) 13.0%-42.1%] with GC versus 20.0% (95% CI 11.9%-30.4%) with GCI,
which did not allow rejection of the null hypothesis (ORR with GCI <=20%; P =
0.545). Median PFS was 4.3 (95% CI 2.8-5.6) months with GC and 5.7 (95% CI 4.6
6.6) months with GCI (hazard ratio 0.89, 95% CI 0.56-1.40). Median OS was 8.5
(95% CI 5.5 to not reached) months with GC, and 12.0 (95% CI 8.9-17.1) months
with GCI (hazard ratio 0.78, 95% CI 0.48-1.27). More GCI patients received second
line treatment (51% GC and 68% GCI). Toxicity was similar in the two arms. Grade
3-4 toxicities included asthenia (28% GC and 8% GCI), nausea (3% GC and 14% GCI),
and decreased appetite (10% in each). CONCLUSIONS: Addition of iniparib to GC did
not improve ORR over GC alone. The GCI safety profile was comparable to GC alone.
Imbalances in PS and gender distribution may have impacted study results
regarding PFS and OS. TRIAL REGISTRATION: ClinicalTrial.gov Identifier
NCT01086254.
PMID- 25139551
TI - Antihypertensive medication exposure and cardiovascular outcomes in hemodialysis
patients.
AB - BACKGROUND/AIMS: Our understanding of the effectiveness of cardioprotective
medications in maintenance dialysis patients is based upon drug exposures
assessed at a single point in time. We employed a novel, time-dependent approach
to modeling medication use over time to examine outcomes in a large national
cohort. METHODS: We linked Medicaid prescription claims with United States Renal
Data System registry data and Medicare claims for 52,922 hypertensive maintenance
dialysis patients. All-cause mortality and a combined cardiovascular disease
(CVD)-endpoint were modeled as functions of exposure to cardioprotective
antihypertensive medications (renin angiotensin system antagonists, beta
adrenergic blockers, and calcium channel blockers) measured with three time
dependent covariates (weekly exposure status, proportion of prior weeks with
exposure, and number of switches in exposure status) and with propensity
adjustment. RESULTS: Current cardioprotective medication exposure status as
compared to not exposed was associated with lower adjusted hazard ratios (AHRs)
for mortality, though the magnitude depended upon the proportion of prior weeks
with medication (duration) and the number of switches between active and non
active use (switches) (AHR range 0.54-0.90). Combined CVD-endpoints depended upon
the proportion of weeks on medication: AHR = 1.18 for 10% and AHR = 0.90 for 90%
of weeks. Combined CVD-endpoint was also lower for patients with fewer switches.
CONCLUSIONS: Effectiveness depends not only on having a drug available but is
tempered by duration and stability of use, likely reflecting variation in
clinical stability and patient behavior.
PMID- 25139552
TI - A Retrospective Review of the Clinical Experience of Linezolid with or Without
Rifampicin in Prosthetic Joint Infections Treated with Debridement and Implant
Retention.
AB - INTRODUCTION: Debridement and prosthesis retention, combined with a prolonged
antibiotic regimen including rifampicin, is an accepted therapeutic approach when
the duration of symptoms is less than 4 weeks and there are no radiological signs
of loosening. The outcome of patients managed with this strategy has been
previously assessed in several articles with success rates of 60-90%. This study
aims to review the clinical experience with linezolid in 3 different hospitals
from Spain and France in patients with prosthetic joint infection (PJI) managed
with debridement, retention of the implant and treated with linezolid with or
without rifampicin. METHODS: Patients with an acute PJI who underwent open
debridement with implant retention treated with linezolid for more than 7 days in
3 hospitals from Barcelona, Tours and Lille between 2005 and 2011 were
retrospectively reviewed. Relevant information about demographics, co-morbidity,
type of implant, surgical treatment, microorganism isolated, antimicrobial
therapy, adverse events (AEs) and outcomes were recorded from patients. RESULTS:
A total of 39 patients were retrospectively reviewed. The mean age (SD) was 70.5
(8.8) years and 9 patients had diabetes mellitus (23%). There were 25 (64%) knee
prostheses, 13 (33%) hips and 1 shoulder (3%). The median interquartile range
(IQR) days from arthroplasty to infection diagnosis was 17 (19-48) and 33 (85%)
cases were diagnosed within the first 60 days. The median (IQR) duration of
antibiotic treatment was 70.5 (34-96) days and the median (IQR) number of days on
linezolid treatment was 44.5 (30-81). AEs were observed in 15 patients (38%),
with gastrointestinal complaints in 8 cases and anemia in 5 being the most
frequent. After a median (IQR) follow-up of 2.5 (1.8-3.6) years, there were 11
failures (28%) (8 relapses and 3 new infections). The failure rate was higher in
the rifampicin group (36% vs. 18%) mainly due to a higher relapse rate (27% vs.
12%) although differences were not statistically significant. CONCLUSION:
Management of acute PJIs with debridement and retention of the implant linezolid,
with or without rifampicin, is associated with a high remission rate and it is an
alternative treatment for infections due to fluoroquinolone and/or rifampicin
resistant staphylococci.
PMID- 25139553
TI - Searching for the molecular benchmark of physiological intestinal anastomotic
healing in rats: an experimental study.
AB - PURPOSE: This investigation focuses on the physiological characteristics of gene
transcription of intestinal tissue following anastomosis formation. METHODS: In
eight rats, end-to-end ileo-ileal anastomoses were performed (n = 2/group). The
healthy intestinal tissue resected for this operation was used as a control. On
days 0, 2, 4 and 8, 10-mm perianastomotic segments were resected. Control and
perianastomotic segments were examined with an Affymetrix microarray chip to
assess changes in gene regulation. Microarray findings were validated using real
time PCR for selected genes. In addition to screening global gene expression, we
identified genes intensely regulated during healing and also subjected our data
sets to an overrepresentation analysis using the Gene Ontology (GO) and Kyoto
Encyclopedia for Genes and Genomes (KEGG). RESULTS: Compared to the control
group, we observed that the number of differentially regulated genes peaked on
day 2 with a total of 2,238 genes, decreasing by day 4 to 1,687 genes and to
1,407 genes by day 8. PCR validation for matrix metalloproteinases-3 and -13
showed not only identical transcription patterns but also analogous regulation
intensity. When setting the cutoff of upregulation at 10-fold to identify genes
likely to be relevant, the total gene count was significantly lower with 55, 45
and 37 genes on days 2, 4 and 8, respectively. A total of 947 GO subcategories
were significantly overrepresented during anastomotic healing. Furthermore, 23
overrepresented KEGG pathways were identified. CONCLUSION: This study is the
first of its kind that focuses explicitly on gene transcription during intestinal
anastomotic healing under standardized conditions. Our work sets a foundation for
further studies toward a more profound understanding of the physiology of
anastomotic healing.
PMID- 25139554
TI - Surgical electronic logbook: A step forward.
AB - INTRODUCTION: The surgical electronic logbook (surgical e-logbook) aims to:
simplify registration of the training activities of surgical residents, and to
obtain reliable and detailed reports about these activities for resident
evaluation. METHODS: The surgical e-logbook is a unique and shared database.
Residents prospectively record their activities in 3 areas: surgical, scientific
and teaching. We can access activity reports that are constantly updated.
RESULTS: Study period using the surgical e-logbook: Between June 2011 and May
2013. Number of surgeries reported: 4,255. Number of surgical procedures
reported: 11,907. Number of surgeries per resident per year reported: 250. Number
of surgical procedures per resident per year reported: 700. Surgical activity as
a primary surgeon during the first year of residency is primarily in emergency
surgery (68,01%) and by laparotomy (97,73%), while during the fifth year of
residency 51,27% is performed in elective surgery and laparoscopy is used in
23,10% of cases. During this period, residents participated in a total of 11
scientific publications, 75 conference presentations and 69 continuing education
activities. CONCLUSIONS: The surgical e-logbook is a useful tool that simplifies
the recording and analysis of data about surgical and scientific activities of
the residents. It is a step forward in the evaluation of the training of surgical
residents, however, is only an intermediate step towards the development of a
larger Spanish registry.
PMID- 25139555
TI - Thoracic aortic cannulation with antegrade perfusion for the procurement of
abdominal organs.
AB - The definitive acceptance of an organ as valid for transplant depends on the
surgical team performing the multiorgan recovery; and unexpected difficulties can
occur. The demographic characteristics of donors has changed, and some accepted
donors can present difficulties in surgical technique and risky decisions on the
validity of the retrieved organ or organs. An alternative method to the
cannulation of the abdominal aorta is proposed when there is evidence of disease
in the infrarenal aorta during the multiorgan procurement. The retrocardiac
descending thoracic aorta is cannulated using an antegrade perfusion; this
technique allows an increase in organ recovery.
PMID- 25139556
TI - Evaluation of the influence of metabolic processes and body composition on
cognitive functions: Nutrition and Dementia Project (NutrDem Project).
AB - The global increase in the prevalence of dementia and its associated
comorbidities and consequences has stimulated intensive research focused on
better understanding of the basic mechanisms and the possibilities to prevent
and/or treat cognitive decline or dementia. The etiology of cognitive decline and
dementia is very complex and is based upon the interplay of genetic and
environmental factors. A growing body of epidemiological evidence has suggested
that metabolic syndrome and its components may be important in the development of
cognitive decline. Furthermore, an abnormal body mass index in middle age has
been considered as a predictor for the development of dementia. The Nutrition and
Dementia Project (NutrDem Project) was started at the Department of Old Age
Psychiatry and Psychotic Disorders with close cooperation with Department of
Medical Psychology. The aim of this study is to determine the effect of dietary
patterns, nutritional status, body composition (with evaluation of visceral fat)
and basic regulatory mechanisms of metabolism in elderly patients on cognitive
functions and the risk of cognitive impairment (mild cognitive impairment and/or
dementia).
PMID- 25139557
TI - Bioelectrical impedance vector analysis (BIVA) for the assessment of two
compartment body composition.
AB - This review is directed to define the efficacy of bioelectrical impedance vector
analysis (BIVA) for assessing two-compartment body composition. A systematic
literature review using MEDLINE database up to 12 February 2014 was performed.
The list of papers citing the first description of BIVA, obtained from SCOPUS,
and the reference lists of included studies were also searched. Selection
criteria included studies comparing the results of BIVA with those of other
techniques, and studies analyzing bioelectrical vectors of obese, athletic,
cachectic and lean individuals. Thirty articles met the inclusion criteria. The
ability of classic BIVA for assessing two-compartment body composition has been
mainly evaluated by means of indirect techniques, such as anthropometry and
bioelectrical impedance analysis (BIA). Classic BIVA showed a high agreement with
body mass index, that can be interpreted in relation to the greater body mass of
obese and athletic individuals, whereas the comparison with BIA showed less
consistent results, especially in diseased individuals. When a reference method
was used, classic BIVA failed to accurately recognize FM% variations, whereas
specific BIVA furnished good results. Specific BIVA is a promising alternative to
classic BIVA for assessing two-compartment body composition, with potential
application in nutritional, sport and geriatric medicine.
PMID- 25139558
TI - Measuring diet in primary school children aged 8-11 years: validation of the
Child and Diet Evaluation Tool (CADET) with an emphasis on fruit and vegetable
intake.
AB - BACKGROUND/OBJECTIVES: The Child And Diet Evaluation Tool (CADET) is a 24-h food
diary that measures the nutrition intake of children aged 3-7 years, with a focus
on fruit and vegetable consumption. Until now CADET has not been used to measure
nutrient intake of children aged 8-11 years. To ensure that newly assigned
portion sizes for this older age group were valid, participants were asked to
complete the CADET diary (the school and home food diary) concurrently with a 1
day weighed record. SUBJECTS/METHODS: A total of 67 children with a mean age of
9.3 years (s.d.: +/- 1.4, 51% girls) participated in the study. Total fruit and
vegetable intake in grams and other nutrients were extracted to compare the mean
intakes from the CADET diary and Weighed record using t-tests and Pearson's r
correlations. Bland-Altman analysis was also conducted to assess the agreement
between the two methods. RESULTS: Correlations comparing the CADET diary to the
weighed record were high for fruit, vegetables and combined fruit and vegetables
(r=0.7). The results from the Bland-Altman plots revealed a mean difference of 54
g (95% confidence interval: -88, 152) for combined fruit and vegetables intake.
CADET is the only tool recommended by the National Obesity Observatory that has
been validated in a U.K. population and provides nutrient level data on
children's diets. CONCLUSIONS: The results from this study conclude that CADET
can provide high-quality nutrient data suitable for evaluating intervention
studies now for children aged 3-11 years with a focus on fruit and vegetable
intake.
PMID- 25139559
TI - Assessment and definition of lean body mass deficiency in the elderly.
AB - Although the effect of age on body composition has been intensively discussed
during the past 20 years, we do not have a uniform definition of sarcopenia. A
suitable definition of low, lean body mass should be based on magnetic resonance
imaging (MRI) estimates of muscle mass. Using recent MRI data of a population of
446 healthy free-living Caucasian volunteers (247 females, 199 males) age 18-78
years, a low skeletal muscle mass and sarcopenia were defined as a skeletal
muscle mass >1 and >2 s.d. below the mean value obeserved in younger adults at
age 18-39 years. The cutoffs for low muscle mass according to the skeletal muscle
index (skeletal muscle mass/(height)(2)) or the appendicular skeletal muscle mass
index (skeletal muscle mass of the limbs/(height)(2)) were 6.75 or 4.36 kg/m(2)
for females and 8.67 or 5.54 kg/m(2) for males, respectively. On the basis of
these cutoffs, prevalences of sarcopenia in the group of adults at >60 years are
calculated to be 29% in females and 19.0% in males. Faced with different
sarcopenic phenotypes (that is, sarcopenia related to frailty and osteopenia;
sarcopenic obesity related to metabolic risks; cachexia related to wasting
diseases), future definitions of sarcopenia should be extended to the relations
between (i) muscle mass and adipose tissue and (ii) muscle mass and bone mass.
Suitable cutoffs should be based on the associations between estimates of body
compositions and metabolic risks (for axample, insulin resistance), inflammation
and muscle function (that is, muscle strength).
PMID- 25139560
TI - Long-term exposure of human gingival fibroblasts to cigarette smoke condensate
reduces cell growth by modulating Bax, caspase-3 and p53 expression.
AB - BACKGROUND AND OBJECTIVE: Smoking cigarettes increases the risk of oral tissue
damage leading to periodontal disease. Gingival fibroblasts, the predominant cell
type inhabiting gingival connective tissue, play a critical role in remodeling
and maintaining gingival structure. The objective of this study was to
investigate the effect of long-term exposure to cigarette smoke on human gingival
fibroblast survival/apoptosis and the molecular pathways involved in these cell
responses. MATERIAL AND METHODS: Human gingival fibroblasts were extracted from
healthy non-smokers and cultured in the presence of cigarette smoke condensate
(CSC). At the end of each time point, cell growth was evaluated by means of MTT
assay. Apoptotic and necrotic gene's expression was investigated by polymerase
chain reaction array and by annexin V/propidium iodide staining and cell cycle
assays. Western blot was used to investigate Bax and p53 proteins. These tests
were supported by caspase 3 activity analyses. RESULTS: High levels of CSC
decreased cell growth and deregulated cell cycle progression by increasing the
G(0)/G(1) and reducing the S and G(2)/M phases of the gingival fibroblasts.
Polymerase chain reaction arrays revealed the activation of several apoptotic
genes by CSC, including TNF receptors, caspases, Bax and p53. This was supported
by increases in the Bax and p53 protein levels as well as by an elevated activity
of caspase-3 in the CSC-exposed cells. Immunofluorescence staining demonstrated
that both Bax and caspase-3 displayed a cytosolic and mitochondrial distribution
in the CSC-exposed gingival fibroblasts, compared to controls. The damaging
effect of CSC on gingival fibroblast growth was also supported by the decrease in
interleukin 6 and 8 secretion by the gingival fibroblasts. CONCLUSION: These
results suggest that CSC may contribute to deregulating fibroblast functions.
This can compromise fibroblast-epithelial cell interactions, which ultimately
increases the risk of gingival tissue damage and the onset of periodontitis.
PMID- 25139561
TI - Tissue-specific actions of FXR in metabolism and cancer.
AB - The nuclear Farnesoid X Receptor (FXR) is a transcription factor critically
involved in metabolic homeostasis in the gut-liver axis. FXR activity is mediated
by hormonal and dietary signals and driven by bile acids (BAs), which are the
natural FXR ligands. Given the great physiological importance in BA homeostasis,
as well as in the regulation of glucose and lipid metabolism, FXR plays a pivotal
role in the pathogenesis of a wide range of disease of the liver, biliary tract
and intestine, including hepatic and colorectal cancer. In the last years several
studies have shown the relative FXR tissue-specific importance, highlighting
synergism and additive effects in the liver and intestine. Gain- and loss-of-FXR
function mouse models have been generated in order to identify the biological
processes and the molecular FXR targets. Taking advantage of the knowledge on the
structure-activity relationship of BAs for FXR, semi-synthetic and synthetic
molecules have been generated to obtain more selective and powerful FXR
activators than BAs. This article is part of a Special Issue entitled: Linking
transcription to physiology in lipodomics.
PMID- 25139563
TI - New and unusual forms of calcium oxalate raphide crystals in the plant kingdom.
AB - Calcium oxalate crystals in higher plants occur in five major forms namely
raphides, styloids, prisms, druses and crystal sand. The form, shape and
occurrence of calcium oxalate crystals in plants are species- and tissue
specific, hence the presence or absence of a particular type of crystal can be
used as a taxonomic character. So far, four different types of needle-like
raphide crystals have been reported in plants. The present work describes two new
and unusual forms of raphide crystals from the tubers of Dioscorea polystachya-
six-sided needles with pointed ends (Type V) and four-sided needles with beveled
ends (Type VI). Both of these new types of needles are distinct from the other
four types by each having a surrounding membrane that envelopes a bundle of 10-20
closely packed thin crystalline sheets. The previously known four types of
needles have solid or homogenous crystalline material, surrounded by a membrane
or lamellate sheath called a crystal chamber. Only the Type VI crystals have
beveled ends and the needles of the other five types have pointed ends.
PMID- 25139562
TI - Protectins and maresins: New pro-resolving families of mediators in acute
inflammation and resolution bioactive metabolome.
AB - Acute inflammatory responses are protective, yet without timely resolution can
lead to chronic inflammation and organ fibrosis. A systems approach to
investigate self-limited (self-resolving) inflammatory exudates in mice and
structural elucidation uncovered novel resolution phase mediators in vivo that
stimulate endogenous resolution mechanisms in inflammation. Resolving
inflammatory exudates and human leukocytes utilize DHA and other n-3 EFA to
produce three structurally distinct families of potent di- and trihydroxy
containing products, with several stereospecific potent mediators in each family.
Given their potent and stereoselective picogram actions, specific members of
these new families of mediators from the DHA metabolome were named D-series
resolvins (Resolvin D1 to Resolvin D6), protectins (including protectin D1
neuroprotectin D1), and maresins (MaR1 and MaR2). In this review, we focus on a)
biosynthesis of protectins and maresins as anti-inflammatory-pro-resolving
mediators; b) their complete stereochemical assignments and actions in vivo in
disease models. Each pathway involves the biosynthesis of epoxide-containing
intermediates produced from hydroperoxy-containing precursors from human
leukocytes and within exudates. Also, aspirin triggers an endogenous DHA
metabolome that biosynthesizes potent products in inflammatory exudates and human
leukocytes, namely aspirin-triggered Neuroprotectin D1/Protectin D1 [AT
(NPD1/PD1)]. Identification and structural elucidation of these new families of
bioactive mediators in resolution has opened the possibility of diverse patho
physiologic actions in several processes including infection, inflammatory pain,
tissue regeneration, neuroprotection-neurodegenerative disorders, wound healing,
and others. This article is part of a Special Issue entitled "Oxygenated
metabolism of PUFA: analysis and biological relevance".
PMID- 25139564
TI - Successful transplantation of kidney allografts in sensitized rats after
syngeneic hematopoietic stem cell transplantation and fludarabine.
AB - Current methods to remove donor-specific HLA antibody (DSA) from sensitized
patients remain imperfect. We tested novel approaches to desensitization using an
animal model of allogeneic sensitization with skin grafts from dark agouti (DA)
to Lewis rats. At the peak IgG alloantibody response we transplanted DA kidneys
into nephrectomized Lewis recipients (n = 6) and all died within 10 days from
antibody-mediated rejection (AMR). Allogeneic hematopoietic stem cell transplants
(HSCT) from DA donors failed to engraft after lethal or sub-lethal irradiation.
Sensitized rats given lethal irradiation plus syngeneic green fluorescent protein
(GFP) + HSCT had repopulation of blood, spleen, thymus and lymph nodes by GFP+
cells. At 2 months after HSCT, serum DSA levels were reduced 60-70% and DSA (IgG)
production in cultured splenocytes was also significantly decreased. However,
there was only a modest improvement in graft survival from an average of 6.5 to
13.9 (n = 9) days. Adding seven daily doses of fludarabine to the preconditioning
regimen resulted in long-term survival (>90 days) in 7 out of 10 rat kidney
allografts. We conclude that syngeneic HSCT performed after preconditioning with
irradiation and fludarabine can reduce DSA, prevent DSA rebound and AMR, enabling
successful transplantation in animals with strong antibody reactivity to the
donor MHC.
PMID- 25139565
TI - Fragment-based identification and optimization of a class of potent pyrrolo[2,1
f][1,2,4]triazine MAP4K4 inhibitors.
AB - MAP4K4 has been shown to regulate key cellular processes that are tied to disease
pathogenesis. In an effort to generate small molecule MAP4K4 inhibitors, a
fragment-based screen was carried out and a pyrrolotriazine fragment with
excellent ligand efficiency was identified. Further modification of this fragment
guided by X-ray crystal structures and molecular modeling led to the discovery of
a series of promising compounds with good structural diversity and
physicochemical properties. These compounds exhibited single digit nanomolar
potency and compounds 35 and 44 achieved good in vivo exposure.
PMID- 25139566
TI - Synthesis of N-glycan units for assessment of substrate structural requirements
of N-acetylglucosaminyltransferase III.
AB - N-Acetylglucosaminyltransferase (GnT) III is a glycosyltransferase which produces
bisected N-glycans by transferring GlcNAc to the 4-position of core mannose.
Bisected N-glycans are involved in physiological and pathological processes
through the functional regulation of their carrier proteins. An understanding of
the biological functions of bisected glycans will be greatly accelerated by use
of specific inhibitors of GnT-III. Thus far, however, such inhibitors have not
been developed and even the substrate-binding mode of GnT-III is not fully
understood. To gain insight into structural features required of the substrate,
we systematically synthesized four N-glycan units, the branching parts of the
bisected and non-bisected N-glycans. The series of syntheses were achieved from a
common core trimannose, giving bisected tetra- and hexasaccharides as well as non
bisected tri- and pentasaccharides. A competitive GnT-III inhibition assay using
the synthetic substrates revealed a vital role for the Manbeta(1-4)GlcNAc moiety.
In keeping with previous reports, GlcNAc at the alpha1,3-branch is also involved
in the interaction. The structural requirements of GnT-III elucidated in this
study will provide a basis for rational inhibitor design.
PMID- 25139567
TI - A specific cytochrome P450 hydroxylase in herboxidiene biosynthesis.
AB - The anti-cholesterol natural product herboxidiene is synthesized by a
noniterative modular polyketide synthase (HerB, HerC and HerD) and three
tailoring enzymes (HerE, HerF and HerG) in Streptomyces chromofuscus A7847. In
this work, the putative monooxygenase HerG was expressed in Escherichia coli and
the purified enzyme was subjected to biochemical studies. It was identified as a
cytochrome P450 enzyme responsible for the stereospecific hydroxylation at C-18.
This enzyme is highly substrate-specific as it efficiently hydroxylates 18-deoxy
25-demethyl-herboxidiene, but showed no activity towards 18-deoxy-herboxidiene.
The kcat/Km value for the HerG-catalyzed hydroxylation of 18-deoxy-25-demethyl
herboxidiene was determined to be 1669.70+/-47.36 M(-1) s(-1). In vitro co
reaction of HerG with the methyltransferase HerF and analysis of the product
formation in S. chromofuscus A7847 revealed that the biosynthetic intermediate 18
deoxy-25-demethyl-herboxidiene is successively hydroxylated at C-18 by HerG and
methylated at 17-OH to yield the final product herboxidiene. The minor metabolite
18-deoxy-hereboxidiene is a byproduct of the biosynthetic pathway.
PMID- 25139568
TI - Synthesis, biological evaluation and molecular modeling study of 2-(1,3,4
thiadiazolyl-thio and 4-methyl-thiazolyl-thio)-quinazolin-4-ones as a new class
of DHFR inhibitors.
AB - A new series of 2-(1,3,4-thiadiazolyl- or 4-methyl-thiazolyl)thio-6-substituted
quinazolin-4-one analogs was designed, synthesized, and evaluated for their in
vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 29, 34,
and 39 proved to be the most active DHFR inhibitors with IC50 values range of 0.1
0.6 MUM. Compounds 28, 31 and 33 showed remarkable broad-spectrum antimicrobial
activity comparable to the known antibiotic Gentamicin. Compounds 26, 33, 39, 43,
44, 50, 55 and 63 showed broad spectrum antitumor activity with GI values range
of 10.1-100%. Molecular modeling study concluded that recognition with key amino
acid Glu30, Phe31 and Phe34 is essential for binding. ADMET properties prediction
of the active compounds suggested that compounds 29 and 34 could be orally
absorbed with diminished toxicity.
PMID- 25139569
TI - Synthesis, biological evaluation and SAR analysis of O-alkylated analogs of
quercetin for anticancer.
AB - O-Alkylated quercetin analogs were synthesized and their anticancer activities
were assessed by a high-throughout screening (HTS) method. The structure-activity
relationships (SAR) showed that introduction of long alkyl chain such as propyl
group at the C-3 OH position or short alkyl chain such as ethyl group at the C-4'
OH position were very important for keeping inhibitory activities against the 16
cancer cell lines. Furthermore, when the two n-butyl groups were introduced into
the C-3, C-7 or C-4', C-7 positions, the anticancer activity was enhanced.
PMID- 25139570
TI - Synthesis and structure-activity relationships of PI3K/mTOR dual inhibitors from
a series of 2-amino-4-methylpyrido[2,3-d]pyrimidine derivatives.
AB - Inhibition of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of
rapamycin (mTOR) signaling pathway by PI3K/mTOR dual inhibitors provides a
promising new approach to the treatment of cancers. In this Letter, we identified
structurally novel and potent PI3K/mTOR dual inhibitors from a series of 2-amino
4-methylpyrido[2,3-d]pyrimidine derivatives. Their synthesis and structure
activity relationships are reported.
PMID- 25139571
TI - Identification of cytidine 2',3'-cyclic monophosphate and uridine 2',3'-cyclic
monophosphate in Pseudomonas fluorescens pfo-1 culture.
AB - Cytidine 2',3'-cyclic monophosphate (2',3'-cCMP) and uridine 2',3'-cyclic
monophosphate (2',3'-cUMP) were isolated from Pseudomonas fluorescens pfo-1 cell
extracts by semi-preparative reverse phase HPLC. The structures of the two
compounds were confirmed by NMR and mass spectroscopy against commercially
available authentic samples. Concentrations of both intracellular and
extracellular 2',3'-cCMP and 2',3'-cUMP were determined. Addition of 2',3'-cCMP
and 2',3'-cUMP to P. fluorescens pfo-1 culture did not significantly affect the
level of biofilm formation in static liquid cultures.
PMID- 25139572
TI - Palladium-templated subcomponent self-assembly of macrocycles, catenanes, and
rotaxanes.
AB - The reaction of 2,6-diformylpyridine with diverse amines and Pd(II) ions gave
rise to a variety of metallosupramolecular species, in which the Pd(II) ion is
observed to template a tridentate bis(imino)pyridine ligand. These species
included a mononuclear complex as well as [2+2] and [3+3] macrocycles. The
addition of pyridine-containing macrocyclic capping ligands allows for
topological complexity to arise, thereby enabling the straightforward preparation
of structures that include a [2]catenane, a [2]rotaxane, and a doubly threaded
[3]rotaxane.
PMID- 25139573
TI - The BODE index, a multidimensional grading system, reflects impairment of right
ventricle functions in patients with chronic obstructive pulmonary disease: a
speckle-tracking study.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is not only
characterized by chronic airflow limitation, but is also a systemic disease.
There is no information about alterations in right ventricle (RV) functions
precipitated by systemic manifestations of COPD. OBJECTIVES: We aimed to evaluate
the relationship between the BODE (body mass index, airflow obstruction, dyspnea,
and exercise capacity) index that evaluates systemic manifestations of COPD and
RV functions by means of 2-dimensional speckle-tracking echocardiography (2D-STE)
in COPD patients. METHODS: The study involved 135 COPD patients and 37 control
subjects. All patients underwent 2D-STE, pulmonary function tests and 6-min walk
tests, and were divided into quartiles according to their calculated BODE index
score. RESULTS: COPD patients had impaired RV and left-ventricle diastolic
functions compared to controls. There was a decreasing trend from quartile 1 (Q1)
to Q4 in RV functional parameters, i.e., RV free wall strain (RVFW-S, p < 0.001),
tricuspid annular plane systolic excursion (p < 0.001), systolic myocardial
velocity (p < 0.001), RV fractional area change (p < 0.001), RV myocardial
performance index (p < 0.001) and pulmonary artery systolic pressure (p < 0.001).
The transmitral Doppler E wave/lateral mitral annular tissue Doppler E wave ratio
was similar in the 4 BODE index quartiles (p = 0.159). Multivariate analysis was
performed to find independent predictors of decreased RVFW-S (<=19.06), and the
BODE index (in quartiles; OR 4.61 and 95% CI 1.85-11.63) was found to be an
independent predictor. In a partial correlation analysis adjusted for forced
expiratory volume in 1s % predicted, RVFW-S was correlated with the 6-min walk
distance (r = 0.498). CONCLUSION: The BODE index, which can be easily evaluated
in office settings, may provide information about reduced RV functions as well as
guiding treatment and helping to predict prognosis in COPD patients.
PMID- 25139574
TI - Postoperative radiation therapy for extramammary Paget's disease.
AB - BACKGROUND: Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy
that is usually treated with surgery. Patients with positive surgical margins
require adjuvant therapy, but there have been few reports on the use of radiation
therapy. OBJECTIVES: To investigate the effectiveness of postoperative radiation
therapy in EMPD. MATERIALS AND METHODS: Twenty-one patients with EMPD involving
the genitalia underwent radiation therapy as adjuvant therapy after surgery. Ten
patients had inguinal lymph node involvement before radiation therapy, but none
had distant metastases. A median total dose of 59.4 Gy (range, 45-64.8 Gy) was
delivered to the tumour bed in 30 fractions (range, 23-36 fractions). RESULTS: At
a median follow-up period of 38 months, all patients had local control. However,
six patients had developed distant metastases 6-43 months after radiation
therapy. The distant metastasis-free rates were 66% at 3 years and 55% at 5
years. Inguinal lymph node involvement was a significant risk factor for distant
metastases. Four patients died 33-58 months after irradiation; the causes of
death were tumour progression in three patients and infectious pneumonia in one.
The overall and cause-specific survival rates were both 92% at 3 years, and 62%
and 71% at 5 years, respectively. No therapy-related toxicities of grade >= 3
were observed. CONCLUSIONS: Postoperative radiation therapy is safe and effective
in maintaining local control in patients with EMPD.
PMID- 25139575
TI - Electrified emotions: Modulatory effects of transcranial direct stimulation on
negative emotional reactions to social exclusion.
AB - Social exclusion, ostracism, and rejection can be emotionally painful because
they thwart the need to belong. Building on studies suggesting that the right
ventrolateral prefrontal cortex (rVLPFC) is associated with regulation of
negative emotions, the present experiment tests the hypothesis that decreasing
the cortical excitability of the rVLPFC may increase negative emotional reactions
to social exclusion. Specifically, we applied cathodal transcranial direct
current stimulation (tDCS) over the rVLPFC and predicted an increment of negative
emotional reactions to social exclusion. In Study 1, participants were either
socially excluded or included, while cathodal tDCS or sham stimulation was
applied over the rVLPFC. Cathodal stimulation of rVLPFC boosted the typical
negative emotional reaction caused by social exclusion. No effects emerged from
participants in the inclusion condition. To test the specificity of tDCS effects
over rVLPFC, in Study 2, participants were socially excluded and received
cathodal tDCS or sham stimulation over a control region (i.e., the right
posterior parietal cortex). No effects of tDCS stimulation were found. Our
results showed that the rVLPFC is specifically involved in emotion regulation and
suggest that cathodal stimulation can increase negative emotional responses to
social exclusion.
PMID- 25139576
TI - Predicting fetal lung maturity using the fetal pulmonary artery Doppler wave
acceleration/ejection time ratio.
AB - OBJECTIVE: To determine whether the acceleration/ejection time ratio of the fetal
main pulmonary artery Doppler waveform (PATET) can accurately predict the results
of fetal lung maturity testing in amniotic fluid. METHODS: We prospectively
studied pregnant women attending our ultrasound unit for clinically indicated
fetal lung maturity testing. An ultrasound examination that included measurement
of the PATET was performed before the results of the amniocentesis were reported.
The results of the PATET and the surfactant/albumin ratio were compared, and a
receiver operating characteristic curve was used to determine the PATET cutoff
with the optimal sensitivity and specificity for predicting surfactant/albumin
ratio results. p < 0.05 was considered statistically significant. RESULTS: Forty
three patients were included in this study. The receiver operating characteristic
curve demonstrated that a PATET cutoff of 0.3149 provided a specificity of 93%
(95% CI 77-98%), a sensitivity of 73% (95% CI 48-89%), a negative predictive
value of 87% (95% CI 70-95%), and a positive predictive value of 85% (95% CI 58
96%) for predicting immature surfactant/albumin ratio results. CONCLUSION: The
PATET may provide a noninvasive means of determining fetal lung maturity with
acceptable levels of sensitivity, specificity, and predictive values.
PMID- 25139577
TI - Nestin expression and glial response in the hippocampus of mice after
trimethyltin treatment.
AB - Nestin is a protein of embryonic intermediate filaments expressed by multipotent
neural stem cells. In the present study, the nestin expression pattern in the
mouse hippocampus 1, 2, 3, 4, and 8 days after treatment with trimethyltin (TMT)
was examined to explore the possible role played by nestin in chemically induced
hippocampal injury. TMT treatment (2.5mg/kg, intraperitoneally) selectively
injured the dentate gyrus (DG) of the mouse hippocampus. The level of hippocampal
mRNA encoding nestin increased significantly 2 and 3 days post-treatment and
thereafter decreased (at 4 and 8 days post-treatment). The level of nestin
protein significantly increased 2 - 4 days post-treatment, particularly in the
injured region of the DG, and predominantly in glial fibrillary acidic protein
positive astrocytes in the hippocampal DG. Ki67-positive proliferating cells were
increased following TMT treatment and co-localized with nestin-positive reactive
astrocytes. Thus, we suggest that nestin contributes to remodeling of the
chemically injured DG via glial scar formation and the alteration of
neurogenesis.
PMID- 25139578
TI - Longitudinal resting state fMRI analysis in healthy controls and premanifest
Huntington's disease gene carriers: a three-year follow-up study.
AB - BACKGROUND: We previously demonstrated that in the premanifest stage of
Huntington's disease (preHD), a reduced functional connectivity exists compared
to healthy controls. In the current study, we look at possible changes in
functional connectivity occurring longitudinally over a period of 3 years, with
the aim of assessing the potential usefulness of this technique as a biomarker
for disease progression in preHD. METHODS: Twenty-two preHD and 17 healthy
control subjects completed resting state functional magnetic resonance imaging
(fMRI) scans in two visits with 3 years in between. Differences in resting state
connectivity were examined for eight networks of interest using FSL with three
different analysis types: a dual regression method, region of interest approach,
and an independent component analysis. To evaluate a possible combined effect of
gray matter volume change and the change in blood oxygenation level dependent
signal, the analysis was performed with and without voxel-wise correction for
gray matter volume. To evaluate possible correlations between functional
connectivity change and the predicted time to disease onset, the preHD group was
classed as preHD-A if >=10.9 years and preHD-B if <10.9 years from predicted
disease onset. Possible correlations between burden of pathology score and
functional connectivity change in preHD were also assessed. Finally, longitudinal
change in whole brain and striatal volumetric measures was assessed in the
studied cohort. RESULTS: Longitudinal analysis of the resting state-fMRI (RS
fMRI) data revealed no differences in the degree of connectivity change between
the groups over a period of 3 years, though a significantly higher rate of
striatal atrophy was found in the preHD group compared to controls in the same
period. DISCUSSION: Based on the results found in this study, the provisional
conclusion is that RS-fMRI lacks sensitivity in detecting changes in functional
connectivity in HD gene carriers prior to disease manifestation over a 3-year
follow-up period.
PMID- 25139579
TI - Chassis organism from Corynebacterium glutamicum--a top-down approach to identify
and delete irrelevant gene clusters.
AB - For synthetic biology applications, a robust structural basis is required, which
can be constructed either from scratch or in a top-down approach starting from
any existing organism. In this study, we initiated the top-down construction of a
chassis organism from Corynebacterium glutamicum ATCC 13032, aiming for the
relevant gene set to maintain its fast growth on defined medium. We evaluated
each native gene for its essentiality considering expression levels, phylogenetic
conservation, and knockout data. Based on this classification, we determined 41
gene clusters ranging from 3.7 to 49.7 kbp as target sites for deletion. 36
deletions were successful and 10 genome-reduced strains showed impaired growth
rates, indicating that genes were hit, which are relevant to maintain biological
fitness at wild-type level. In contrast, 26 deleted clusters were found to
include exclusively irrelevant genes for growth on defined medium. A combinatory
deletion of all irrelevant gene clusters would, in a prophage-free strain,
decrease the size of the native genome by about 722 kbp (22%) to 2561 kbp.
Finally, five combinatory deletions of irrelevant gene clusters were
investigated. The study introduces the novel concept of relevant genes and
demonstrates general strategies to construct a chassis suitable for
biotechnological application.
PMID- 25139580
TI - Efficacy of interleukin-1 targeting treatments in patients with familial
mediterranean Fever.
AB - Herein, we reported our experience in colchicine-resistant familial Mediterranean
fever (FMF) patients who are treated with anti-interleukin-1 (IL-1) drugs. A
retrospective review of medical records of anti-IL-1 recipients was performed.
The main clinical characteristics of these patients and the evolution after anti
IL-1 were recorded. There were 20 patients (11 male [M] and 9 female [F]).
Despite regular colchicine treatment, median number of attacks per month and per
year was 1 (1-4) and 12 (4-50), respectively. Twelve patients were receiving
anakinra, and eight patients were treated with canakinumab. The number of monthly
and yearly attacks after IL-1 treatment was significantly decreased after the
biologic agent (p < 0.05). One patient did not respond to the treatment, and one
patient developed serious infection during anti-IL-1. We also observed a
significant decrease in proteinuria in the amyloidosis complicated FMF patients.
Anti-IL-1 targeting drugs seem safe and effective therapies in colchicine
resistant FMF.
PMID- 25139581
TI - Flavonoids inhibit COX-1 and COX-2 enzymes and cytokine/chemokine production in
human whole blood.
AB - Cyclooxygenase 2 (COX-2) and the production of cytokines/chemokines are important
targets for the modulation of the inflammatory response. Although a large variety
of inhibitors of these pathways have been commercialized, some of those
inhibitors present severe side effects, governing the search for new molecules,
as alternative anti-inflammatory agents. This study was undertaken to study an
hitherto not evaluated group of flavonoids, concerning its capacity to inhibit
COX-1 and COX-2 enzymes, as well as to inhibit the production of the cytokines
and a chemokine, in a complex matrix involved in the systemic inflammatory
process, the blood, aiming the establishment of a structure-activity
relationship. The results obtained reveal promising flavonoids for the modulation
of the inflammatory process, namely the ones presenting a catechol group in B
ring, as some flavonoids were able to simultaneously inhibit the production of
inflammatory prostaglandin E2 and pro-inflammatory cytokines.
PMID- 25139582
TI - Omentin changes following bariatric surgery and predictive links with biomarkers
for risk of cardiovascular disease.
AB - BACKGROUND: Although no receptor has yet been identified, changes in circulating
levels of the adipokine designated as Omentin have been demonstrated in obesity
and related comorbidities such as cardiovascular disease, insulin resistance,
metabolic syndrome and chronic inflammation. METHODS: Changes in Omentin levels
at 1 and 5 days and 6 and 12 months in response to biliopancreatic diversion with
duodenal switch bariatric surgery were evaluated, specifically to investigate if
changes preceded gain of insulin sensitivity. RESULTS: Pre-operative plasma
Omentin was not different between men (n = 18) vs women (n = 48), or diabetic
status but correlated with body mass index (BMI). Altogether, Omentin increased
as early as 24-h post-surgery, with changes maintained up to 1-year. Fifty-nine
percent of subjects increased Omentin >10% by 24-H following surgery (OmentinINC
p < 0.0001), while 18% of subjects decreased (OmentinDEC p < 0.0001), with
changes maintained throughout one-year. These two groups had comparable age, sex
distribution, diabetes, BMI, waist circumference and fat mass, however OmentinDEC
had elevated levels of cardiovascular risk markers; homocysteine (p = 0.019), NT
proBNP (p = 0.006) and total bilirubin (p = 0.0001) while red blood cell (RBC)
count was lower (p = 0.0005) over the one-year period. Omentin levels at 1-DAY
also correlated with immune parameters (white blood cell count, % neutrophil, %
monocytes, % lymphocytes). CONCLUSION: OmentinDEC at 1 day following surgery may
be a marker of cardiovascular "at-risk" group before weight loss or insulin
sensitivity restoration.
PMID- 25139583
TI - Tissue multifractality and Born approximation in analysis of light scattering: a
novel approach for precancers detection.
AB - Multifractal, a special class of complex self-affine processes, are under recent
intensive investigations because of their fundamental nature and potential
applications in diverse physical systems. Here, we report on a novel light
scattering-based inverse method for extraction/quantification of multifractality
in the spatial distribution of refractive index of biological tissues. The method
is based on Fourier domain pre-processing via the Born approximation, followed by
the Multifractal Detrended Fluctuation Analysis. The approach is experimentally
validated in synthetic multifractal scattering phantoms, and tested on biopsy
tissue slices. The derived multifractal properties appear sensitive in detecting
cervical precancerous alterations through an increase of multifractality with
pathology progression, demonstrating the potential of the developed methodology
for novel precancer biomarker identification and tissue diagnostic tool. The
novel ability to delineate the multifractal optical properties from light
scattering signals may also prove useful for characterizing a wide variety of
complex scattering media of non-biological origin.
PMID- 25139584
TI - Factors affecting chronic pain and increases of analgesic drug consumption after
knee arthroplasty.
PMID- 25139585
TI - Pain therapy with high risk: one-sided presentation of the results from the
latest phase III study on tanezumab in osteoarthritis pain.
PMID- 25139586
TI - Evidence for efficacy of acute treatment of episodic tension-type headache:
methodological critique of randomised trials for oral treatments.
AB - The International Headache Society (IHS) provides guidance on the conduct of
trials for acute treatment of episodic tension-type headache (TTH), a common
disorder with considerable disability. Electronic and other searches identified
randomised, double-blind trials of oral drugs treating episodic TTH with moderate
or severe pain at baseline, or that tested drugs at first pain onset. The aims
were to review methods, quality, and outcomes reported (in particular the IHS
recommended primary efficacy parameter pain-free after 2 hours), and to assess
efficacy by meta-analysis. We identified 58 reports: 55 from previous reviews and
searches, 2 unpublished reports, and 1 clinical trial report with results. We
included 40 reports of 55 randomised trials involving 12,143 patients. Reporting
quality was generally good, with potential risk of bias from incomplete outcome
reporting and small size; the 23 largest trials involved 82% of patients. Few
trials reported IHS outcomes. The number needed to treat values for being pain
free at 2 hours compared with placebo were 8.7 (95% confidence interval [CI] 6.2
to 15) for paracetamol 1000 mg, 8.9 (95% CI 5.9 to 18) for ibuprofen 400mg, and
9.8 (95% CI 5.1 to 146) for ketoprofen 25mg. Lower (better) number needed to
treat values were calculated for outcomes of mild or no pain at 2 hours, and
patient global assessment. These were similar to values for these drugs in
migraine. No other drugs had evaluable results for these patient-centred
outcomes. There was no evidence that any one outcome was better than others. The
evidence available for treatment efficacy is small in comparison to the size of
the clinical problem.
PMID- 25139587
TI - Challenges and cautions with small and retrospective postoperative pain genome
wide association studies with TAOK3.
PMID- 25139588
TI - Affective disturbance associated with premenstrual dysphoric disorder does not
disrupt emotional modulation of pain and spinal nociception.
AB - In healthy individuals, emotions modulate pain and spinal nociception according
to a valence linear trend (ie, pain/nociception is highest during negative
emotions and lowest during positive emotions). However, emerging evidence
suggests that emotional modulation of pain (but not spinal nociception) is
disrupted in fibromyalgia and disorders associated with chronic pain risk (eg,
major depression, insomnia). The present study attempted to extend this work and
to examine whether women with premenstrual dysphoric disorder (PMDD), a cyclical
syndrome associated with debilitating affective symptoms during the late-luteal
(premenstrual) phase of the menstrual cycle, is also associated with disrupted
emotional modulation of pain. To do so, an affective picture-viewing procedure
was used to study emotional modulation of pain and spinal nociception in 14 women
with PMDD and 14 control women during mid-follicular, ovulatory, and late-luteal
phases of the menstrual cycle (verified by salivary hormone levels and
luteinizing hormone tests). At each phase, mutilation, neutral, and erotic
pictures were presented to manipulate emotion. During picture viewing,
suprathreshold electrocutaneous stimuli were presented to evoke pain and the
nociceptive flexion reflex (NFR; a physiological measure of spinal nociception).
Statistically powerful linear mixed model analyses confirmed that pictures evoked
the intended emotional states in both groups across all menstrual phases.
Furthermore, emotion modulated pain and NFR according to a valence linear trend
in both groups and across all menstrual phases. Thus, PMDD-related affective
disturbance is not associated with a failure to emotionally modulate pain,
suggesting that PMDD does not share this pain phenotype with major depression,
insomnia, and fibromyalgia.
PMID- 25139589
TI - The effect of oxcarbazepine in peripheral neuropathic pain depends on pain
phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified
study.
AB - In neuropathic pain it has been suggested that pain phenotype based on putative
pain mechanisms may predict response to treatment. This was a randomised, double
blind, placebo-controlled, and phenotype-stratified study with 2 6-week treatment
periods of oxcarbazepine (1800-2400mg) and placebo. The primary efficacy measure
was change in median pain intensity between baseline and the last week of
treatment measured on an 11-point numeric rating scale, and the primary objective
was to compare the effect of oxcarbazepine in patients with and without the
irritable nociceptor phenotype as defined by hypersensitivity and preserved small
nerve fibre function determined by detailed quantitative sensory testing. Ninety
seven patients with peripheral neuropathic pain due to polyneuropathy, surgical
or traumatic nerve injury, or postherpetic neuralgia were randomised. The
intention-to-treat population comprised 83 patients: 31 with the irritable and 52
with the nonirritable nociceptor phenotype. In the total sample, oxcarbazepine
relieved pain of 0.7 points (on a numeric rating scale 0-10; 95% confidence
interval [CI] 0.4-1.4) more than placebo (P=0.015) and there was a significant
interaction between treatment and phenotype of 0.7 (95% CI 0.01-1.4, P=0.047).
The number needed to treat to obtain one patient with more than 50% pain relief
was 6.9 (95% CI 4.2-22) in the total sample, 3.9 (95% CI 2.3-12) in the
irritable, and 13 (95% CI 5.3-infinity) in the nonirritable nociceptor phenotype.
In conclusion, oxcarbazepine is more efficacious for relief of peripheral
neuropathic pain in patients with the irritable vs the nonirritable nociceptor
phenotype.
PMID- 25139590
TI - Nox2-dependent signaling between macrophages and sensory neurons contributes to
neuropathic pain hypersensitivity.
AB - Emerging lines of evidence indicate that production of reactive oxygen species
(ROS) at distinct sites of the nociceptive system contributes to the processing
of neuropathic pain. However, the mechanisms underlying ROS production during
neuropathic pain processing are not fully understood. We here detected the ROS
generating nicotinamide adenine dinucleotide phosphate oxidase isoform Nox2 in
macrophages of dorsal root ganglia (DRG) in mice. In response to peripheral nerve
injury, Nox2-positive macrophages were recruited to DRG, and ROS production was
increased in a Nox2-dependent manner. Nox2-deficient mice displayed reduced
neuropathic pain behavior after peripheral nerve injury, whereas their immediate
responses to noxious stimuli were normal. Moreover, injury-induced upregulation
of tumor necrosis factor alpha was absent, and activating transcription factor 3
induction was reduced in DRG of Nox2-deficient mice, suggesting an attenuated
macrophage-neuron signaling. These data suggest that Nox2-dependent ROS
production in macrophages recruited to DRG contributes to neuropathic pain
hypersensitivity, underlining the observation that Nox-derived ROS exert specific
functions during the processing of pain.
PMID- 25139591
TI - Supraspinal TRPV1 modulates the emotional expression of abdominal pain.
AB - The transient receptor potential vanilloid receptor type-1 (TRPV1) is critically
involved in peripheral nociceptive processes of somatic and visceral pain.
However, the role of the capsaicin receptor in the brain regarding visceral pain
remains elusive. Here, we studied the contribution of TRPV1 to abdominal pain
transmission at different nociceptive pathway levels using TRPV1 knock-out mice,
resiniferatoxin-mediated deletion of TRPV1-positive primary sensory neurons, and
intracerebral TRPV1 antagonism. We found that constitutive genetic TRPV1 deletion
or peripheral TRPV1 deletion reduced acetic acid-evoked abdominal constrictions,
without affecting referred abdominal hyperalgesia or allodynia in an acute
pancreatitis model of visceral pain. Notably, intracerebral TRPV1 antagonism by
SB 366791 significantly reduced chemical and inflammatory spontaneous abdominal
nocifensive responses, as observed by reduced expressions of nociceptive facial
grimacing, illustrating the affective component of pain. In addition to the
established role of cerebral TRPV1 in anxiety, fear, or emotional stress, we
demonstrate here for the first time that TRPV1 in the brain modulates visceral
nociception by interfering with the affective component of abdominal pain.
PMID- 25139592
TI - Dyspneic athlete.
AB - Breathing concerns in athletes are common and can be due to a wide variety of
pathology. The most common etiologies are exercise-induced bronchoconstriction
(EIB) and paradoxic vocal fold movement disorder (PVFMD). Although some patients
may have both, PVFMD is often misdiagnosed as EIB, which can lead to unnecessary
treatment. The history and physical exam are important to rule out life
threatening pulmonary and cardiac causes as well as common conditions such as
gastroesophageal reflux disease, sinusitis, and allergic etiologies. The history
and physical exam have been shown to be not as vital in diagnosing EIB and PVFMD.
Improvement in diagnostic testing with office base spirometry, bronchoprovocation
testing, eucapnic voluntary hyperpnea (EVH) and video laryngoscopy are essential
in properly diagnosing these conditions. Accurate diagnosis leads to proper
management, which is essential to avoid unnecessary testing and save healthcare
costs. Also important to the physician treating dyspnea in athletes is knowing
regulations on medications, drug testing, and proper documentation needed for
certain organizations. The differential diagnosis of dyspnea is broad and is not
limited to EIB and PVFMD. Ruling out life threatening cardiac and pulmonary
causes with a proper history, physical, and appropriate testing is essential. The
purpose of this review is to highlight recent literature on the diagnosis and
management of EIB and PVFMD as well as discuss other potential causes for dyspnea
in the athlete.
PMID- 25139593
TI - Do thrombotic events during endovascular interventions lead to poorer outcomes in
patients with severe limb ischemia?
AB - INTRODUCTION: Intra-procedural acute thrombosis (IPAT) is a complication of
endovascular procedures. We aim to identify risk factors for IPAT and compare the
outcomes of patients with or without IPAT. METHODS: Paired T test and chi (2)
test were used to identify risk factors and short-term outcomes. Kaplan-Meier
survival analysis was used for mid-term outcomes. RESULTS: A total of 228
procedures were performed with 21 IPAT events (9.21%). The odds ratio of Indian
patients developing IPAT was 2.8x (95% CI 1.1-7.6). Patients with in-stent
occlusion or prior IPAT were 5.6x (95% CI 1.3-24.2) and 5.6x (95% CI 1.3-24.4)
more likely to develop an IPAT event. Patients without IPAT had significantly
more improvement in mean runoff score (-1.15 +/- 1.31, p < 0.01). The odds of
patients with IPAT requiring subsequent endovascular intervention and arterial
bypass surgery were 4.2x (95% CI 1.6-10.7) and 7.1x (95% CI 1.9-27.0). There was
no significant Kaplan-Meier estimated overall survival or amputation-free
survival difference between patients with or without IPAT event. CONCLUSION:
Indian ethnicity, in-stent occlusion and previous IPAT were associated with
higher risk of IPAT. Even after successful endovascular salvage, patients with
IPATs were more likely to require secondary revascularization procedure. Patients
with IPATs had no decrease in overall survival or amputation-free survival.
PMID- 25139594
TI - Wound debridement optimisation.
AB - Wound debridement, the removal of contaminated tissue and senescent cells, is the
cornerstone in the care of patients with chronic wounds.
PMID- 25139595
TI - Device-related atypical pressure ulcer after cardiac surgery.
AB - Medical devices must be closely monitored to prevent harm to patients. Pressure
ulcers secondary to medical devices present a significant health burden in terms
of length of stay in hospital and cost. Intensivists, anaesthetists and other
professionals involved in managing critically ill patients following cardiac
surgery need to be aware that pressure ulcers may develop in atypical sites and
present at a later stage of the hospital stay. This case report highlights the
important issue of device-related pressure ulcers in the cardiac surgical
intensive care setting, particularly when the clinical status of the patient may
preclude routine assessment and prophylaxis. An algorithm for preventing such
pressure ulcers is suggested.
PMID- 25139596
TI - The use of immunosuppressive agents in the management of recalcitrant lower limb
ulcers.
AB - OBJECTIVE: Lower limb ulcers that are resistant to standard forms of treatment
place a significant burden on both patients and health services. There is no
widely agreed definition of a recalcitrant ulcer but failure to heal following 6
12 months of focused treatment would identify a small group of patients with
highly resistant ulceration. We describe a series of patients with recalcitrant
ulceration for which immunosuppressive agents have been used. METHODS: This is a
case series of 13 patients who underwent immunomodulation therapy for lower limb
ulcers at a tertiary referral university hospital. Regimens of immunomodulation
used mainly ciclosporin and/or cyclophosphamide, with concurrent antibiotic
therapy. Case notes and computer systems were analysed by two reviewers. A
patient was deemed to have a success if their ulcer fully healed while on
immunomodulation therapy. RESULTS: Over a period of eight years, from 2004-2012,
13 patients underwent immunomodulation therapy. Among these patients there were
18 ulcerated limbs. Ulcer healing occurred in 10 limbs out of 18 (55.6%) and full
healing occurred in six patients (46.2%). Ulcers were present for a median of
five years (range 2-40 years), with a median diameter of 7.5 cm (range 4-18 cm)
before treatment. CONCLUSION: Treatment of truly recalcitrant ulceration can be
very frustrating for both the patient and physician, with poor success from more
standard forms of treatment. We report experience with immunomodulation therapy
that suggests there may be benefit from using this treatment in a subset of
patients with this debilitating disease.
PMID- 25139597
TI - A novel approach to the treatment of diabetic foot abscesses - a case series.
AB - Diabetic foot abscesses are an occasional complication of diabetic foot
infections usually involving osteomyelitis and significant soft tissue injury.
The standard of care for diabetic foot abscesses is the performance of immediate
surgical drainage and debridement. However, this therapeutic mode involves more
often than not, some extent of minor amputation and bony loss. With the advent of
new therapeutic techniques it may be possible to treat diabetic foot abscesses
conservatively. OBJECTIVE: To explore adjunct therapies in the treatment of
diabetic foot abscesses in order to avoid extensive surgery, amputation and
tissue loss whilst maintaining limb integrity. METHOD AND RESULTS: Between
January 2011 and June 2012, six patients with a diabetic foot abscess and
osteomyelitis presented at our diabetic foot clinic. They were treated with
topical oxygen and the abscesses were drained using PolyMem(r) Wic(r) Silver Rope
(PWSR). All patients experienced full recovery and remained disease free during a
follow up period of 4-21 months. CONCLUSION: Amputation and the removal of
infected bone had once been considered the sole treatment for diabetic foot
osteomyelitis. Multiple case series and accumulation of clinical experience has
shown otherwise, and nowadays medical management of osteomyelitis is the
preferred treatment in select patients. In our study, we present a case series of
patients suffering from diabetic foot abscesses treated non-surgically. Hopefully
this series will lay the foundation for further data demonstrating the
feasibility of a conservative approach for diabetic foot abscesses, which may
overcome the infection without requiring amputation.
PMID- 25139598
TI - Momordica charantia ointment accelerates diabetic wound healing and enhances
transforming growth factor-beta expression.
AB - OBJECTIVE: Transforming growth factor-beta (TGF-beta) plays an important role in
wound healing. Delayed wound healing is a consequence of diabetes, leading to
high morbidity and poor quality of life. Momordica charantia (MC) fruit possesses
anti-diabetic and wound healing properties. This study aimed to explore the
changes in TGF-beta expression in diabetic wounds treated with topical MC fruit
extract. METHODS: Fifty-six male Sprague-Dawley rats were divided into a normal
control group and five diabetic groups of ten rats each. Intravenous
streptozotocin (50mg/kg) was given to induce diabetes in the diabetic groups.
Full thickness excision wounds were created on the thoracodorsal region of the
animals, and these wounds were then treated with vehicle, MC powder, MC ointment
and povidone ointment or ointment base for ten days. Wound healing was determined
by the rate of wound closure, total protein content and TGF-beta expression in
the wounds, and histological observation. RESULTS: Diabetic groups showed delayed
wound closure rates compared to the control group. The wound closure rate in the
MC ointment group was significantly faster than that of the untreated diabetic
group (p<0.05). The MC ointment group also showed intense TGF-beta expression and
a high level of total protein content. CONCLUSION: MC ointment has a promising
potential for use as an alternative topical medication for diabetic wounds. This
work has shown that it accelerates wound healing in diabetic rats, and it is
suggested here that this occurs by enhancing TGF-beta expression. Further work is
recommended to explore this effect.
PMID- 25139599
TI - Effects of SertaSil on wound healing in the rat.
AB - OBJECTIVE: SertaSil is a novel product for the topical management of wound
exudate. The purpose of this study was to evaluate the ability of SertaSil to
promote wound healing in a pre-clinical wound model. METHODS: An aseptic wound
was induced in rats by administering 1ml 10% calcium chloride solution into the
subcutaneous layer under local anaesthesia. Following opening of the abscess,
animals were divided into a control group (no treatment) and either SertaSil or
Gentaxane, which were applied topically to the wound every 24 hours until a clean
wound was achieved, that is, free from necrosis, pus and fibrinogenous
thickenings. RESULTS: Rats (n=15 per group) receiving SertaSil reached the clean
wound stage in 3.0 +/- 0.4 days compared to 7.0 +/- 0.4 days for Gentaxane and
10.0 +/- 0.4 days for the control. Time to wound closure was 13.9 +/- 0.3 days
for SertaSil, 18.7 +/- 0.6 days for Gentaxane, and 23.0 +/- 0.4 days for the
control. The surface area of the wounds were measured at day 1 and day 13. At day
1, the wound surface areas (mm2) were similar in all three groups (157.4 +/-
8.9), but at day 13 the SertaSil group had significantly smaller wound areas (5.2
+/- 1.7) compared to the Gentaxane (38.0 +/- 1.5) and control groups (95.7 +/-
11.3). The study was conducted in young rats that are still growing and gaining
weight. At day 19, only the rats receiving SertaSil exhibited a weight increase
(271 +/- 5 g) indicating good recovery, whereas rats receiving Gentaxane did not
gain weight (249 +/- 5 g) and rats in the control group lost weight (242 +/- 16
g). CONCLUSION: The study found that SertaSil reduced the time to reaching a
clean wound by 60% compared to Gentaxane and promoted faster wound closure and
better recovery. These findings suggest that SertaSil may be valuable for use in
the treatment of wounds in patients.
PMID- 25139600
TI - Adhesion of the ulcerative pathogen Mycobacterium ulcerans to DACC-coated
dressings.
AB - OBJECTIVE: Mycobacterium ulcerans is the causative agent of Buruli ulcer disease,
the third most common mycobacteriosis after tuberculosis and leprosy and an
emerging public health threat in sub-Saharan Africa. The bacteria produce a
diffusible cytotoxin called mycolactone, which triggers the formation of necrotic
lesions in cutaneous and subcutaneous tissues. The principal aim of this study
was to characterise the cell surface hydrophobicity of Mycobacterium ulcerans and
determine if bacteria bind to dialkyl carbamoyl chloride (DACC)-coated dressings
through hydrophobic interactions in vitro. Since mycolactone displays hydrophobic
groups, a secondary aim was to compare mycolactone binding to hydrophobic and
standard dressings. METHODS: We used hydrophobic interaction chromatography to
evaluate the cell surface hydrophobicity of Mycobacterium ulcerans, compared to
that of other microorganisms colonising wounds. The binding of Mycobacterium
ulcerans bacteria to DACC-coated and control dressings was then assessed
quantitatively by measurement of microbial adenosine triphosphate (ATP), while
that of mycolactone was evaluated by fluorescence spectroscopy. RESULTS: Compared
to Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa,
Mycobacterium ulcerans displayed the highest cell surface hydrophobicity,
irrespective of the bacterial production of mycolactone. Mycobacterium ulcerans
bacteria bound to DACC-coated dressings [corrected] better than untreated
controls. Mycolactone did not bind stably to hydrophobic, nor standard dressings,
in the conditions tested. CONCLUSION: Retention of Mycobacterium ulcerans and
other wound pathogens to DACC-coated dressings may help reduce the bacterial load
in Buruli ulcers and thereby improve healing. Dressings efficiently capturing
mycolactone may bring an additional clinical benefit, by accelerating the
elimination of the toxin during the course of antibiotic treatment.
PMID- 25139601
TI - Biofilms in wounds: the chicken or the egg?
PMID- 25139602
TI - Issues, following cancer treatment, that patients would like to discuss at their
review consultation.
PMID- 25139605
TI - The poet, his poem, and the surgeon: the stories behind the enduring appeal of
Invictus.
PMID- 25139606
TI - Effect of instructor feedback on skills retention after laparoscopic simulator
training: follow-up of a randomized trial.
AB - BACKGROUND: Instructor feedback reduces the number of repetitions and time to
reach proficiency during laparoscopic simulator training. The objective of this
study was to examine the effect of instructor feedback on long-term skill
retention. METHODS: A 6-month follow-up of a randomized trial. Participants were
surgical novices (medical students). All participants (n = 99) initially
practiced a laparoscopic salpingectomy on the LapSim virtual reality simulator to
proficiency. The intervention group could request instructor feedback, whereas
the control group could not. After 6 months, the participants (n = 65) practiced
on the simulator until they reached proficiency again. The primary outcomes were
the total time and the number of repetitions. RESULTS: Initially, the
intervention group used significantly fewer repetitions (29 vs 65, p < 0.0005)
and less total training time (162 vs 342 min, p < 0.0005) than the control group
to reach the proficiency level. At follow-up, both the groups used an equal
number of repetitions (21 vs 20, p = 0.72) and time (83 vs 73 min, p = 0.37) to
reach the same proficiency level. CONCLUSIONS: Instructor feedback during
proficiency-based laparoscopic simulator training does not affect the long-term
retention of skills.
PMID- 25139607
TI - Measuring general surgery residents' communication skills from the patient's
perspective using the Communication Assessment Tool (CAT).
AB - OBJECTIVE: The Communication Assessment Tool (CAT) has been used and validated to
assess Family and Emergency Medicine resident communication skills from the
patient's perspective. However, it has not been previously reported as an outcome
measure for general surgery residents. The purpose of this study is to establish
initial benchmarking data for the use of the CAT as an evaluation tool in an
osteopathic general surgery residency program. Results are analyzed quarterly and
used by the program director to provide meaningful feedback and targeted goal
setting for residents to demonstrate progressive achievement of interpersonal and
communication skills with patients. DESIGN: The 14-item paper version of the CAT
(developed by Makoul et al. for residency programs) asks patients to anonymously
rate surgery residents on discrete communication skills using a 5-point rating
scale immediately after the clinical encounter. Results are reported as the
percentage of items rated as "excellent" (5) by the patient. SETTING: The setting
is a hospital-affiliated ambulatory urban surgery office staffed by the residency
program. PARTICIPANTS: Participants are representative of adult patients of both
sexes across all ages with diverse ethnic backgrounds. They include preoperative
and postoperative patients, as well as those needing diagnostic testing and
follow-up. RESULTS: Data have been collected on 17 general surgery residents from
a single residency program representing 5 postgraduate year levels and 448
patient encounters since March 2012. The reliability (Cronbach alpha) of the tool
for surgery residents was 0.98. The overall mean percentage of items rated as
excellent was 70% (standard deviations = 42%), with a median of 100%.
CONCLUSIONS: The CAT is a useful tool for measuring 1 facet of resident
communication skills-the patient's perception of the physician-patient encounter.
The tool provides a unique and personalized outcome measure for identifying
communication strengths and improvement opportunities, allowing residents to
receive specific feedback and mentoring by program directors.
PMID- 25139608
TI - Fast redox-triggered shuttling motions in a copper rotaxane based on a
phenanthroline-terpyridine conjugate.
AB - Fast shuttling motions in solution have been observed by cyclic voltammetry in a
Cu(I/II)-based [2] rotaxane. In the reported system, the different coordination
preferences of both copper oxidation states are exploited to promote the
electrochemically-triggered gliding of the ring from a tetra to a
pentacoordinated site and vice versa. The thread of this rotaxane consists of a
tridentate 2,2':6',2''-terpyridine chelating unit directly bonded through its 5
position to the 3-position of the bidentate 1,10-phenanthroline unit. This
distribution reduces to a minimum the distance between the two coordination sites
and lessens the congestion around the tetrahedral environment. These two factors
have been demonstrated to highly increase the kinetics of the switching process.
In addition, the electrochemical experiments carried out in different solvent
mixtures evidenced the influence of the solvent on the shuttling mechanism.
PMID- 25139609
TI - Insulin treatment guided by subcutaneous continuous glucose monitoring compared
to frequent point-of-care measurement in critically ill patients: a randomized
controlled trial.
AB - INTRODUCTION: Glucose measurement in intensive care medicine is performed
intermittently with the risk of undetected hypoglycemia. The workload for the ICU
nursing staff is substantial. Subcutaneous continuous glucose monitoring (CGM)
systems are available and may be able to solve some of these issues in critically
ill patients. METHODS: In a randomized controlled design in a mixed ICU in a
teaching hospital we compared the use of subcutaneous CGM with frequent point of
care (POC) to guide insulin treatment. Adult critically ill patients with an
expected stay of more than 24 hours and in need of insulin therapy were included.
All patients received subcutaneous CGM. CGM data were blinded in the control
group, whereas in the intervention group these data were used to feed a
computerized glucose regulation algorithm. The same algorithm was used in the
control group fed by intermittent POC glucose measurements. Safety was assessed
with the incidence of severe hypoglycemia (<2.2 mmol/L), efficacy with the
percentage time in target range (5.0 to 9.0 mmol/L). In addition, we assessed
nursing workload and costs. RESULTS: In this study, 87 patients were randomized
to the intervention and 90 to the control group. CGM device failure resulted in
78 and 78 patients for analysis. The incidence of severe glycemia and percentage
of time within target range was similar in both groups. A significant reduction
in daily nursing workload for glucose control was found in the intervention group
(17 versus 36 minutes; P <0.001). Mean daily costs per patient were significantly
reduced with EUR 12 (95% CI -32 to -18, P = 0.02) in the intervention group.
CONCLUSIONS: Subcutaneous CGM to guide insulin treatment in critically ill
patients is as safe and effective as intermittent point-of-care measurements and
reduces nursing workload and daily costs. A new algorithm designed for frequent
measurements may lead to improved performance and should precede clinical
implementation. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01526044. Registered 1
February 2012.
PMID- 25139610
TI - Rituximab in the treatment of autoimmune haemolytic anaemia.
AB - Rituximab is a B-cell depleting monoclonal antibody that is gaining popularity as
an effective therapy for many autoimmune cytopenias. This article systematically
evaluates its therapeutic efficacy in the treatment of different types of
autoimmune haemolytic anaemia. We conclude that there is sufficient evidence to
recommend it as a second line therapy for warm autoimmune haemolytic anaemia
(wAIHA) either as monotherapy or combined therapy. Evidence from a single
randomized controlled trial suggests that it may also be more efficacious as
first line therapy in combination with steroids than steroids alone. A fewer
number of studies have assessed its role in cold autoimmune haemolytic anaemia
(cAIHA) and cold agglutinin disease (CAD) with success rates varying from 45-66%.
In the absence of alternative definitive therapy, rituximab should be considered
for patients with symptomatic CAD and significant haemolysis. Case reports of its
efficacy in mixed autoimmune haemolytic anaemias are available but evidence from
case series or larger cohorts are nonexistent.
PMID- 25139611
TI - Density functional studies on (NCH)n azagraphane: activated surface for
organocatalysis.
AB - Quantum chemical analysis shows aza-graphane isomers, with alternate C-H and N:
sites as ideal organocatalysts; their kinetic stability arises from the tertiary
orthoamide. DFT calculations give split-off bands originating from nitrogen lone
pairs with substantial mixing of hydrogen, indicating an optimal balance between
nitrogen basicity and C-H activation through the anomeric effect.
PMID- 25139612
TI - Implementation of evidence-based HIV interventions for young adult African
American women in church settings.
AB - OBJECTIVE: To assess the barriers and facilitators to using African American
churches as sites for implementation of evidence-based HIV interventions among
young African American women. DESIGN: Mixed methods cross-sectional design.
SETTING: African American churches in Philadelphia, PA. PARTICIPANTS: 142 African
American pastors, church leaders, and young adult women ages 18 to 25. METHODS:
Mixed methods convergent parallel design. RESULTS: The majority of young adult
women reported engaging in high-risk HIV-related behaviors. Although church
leaders reported willingness to implement HIV risk-reduction interventions, they
were unsure of how to initiate this process. Key facilitators to the
implementation of evidence-based interventions included the perception of the
leadership and church members that HIV interventions were needed and that the
church was a promising venue for them. A primary barrier to implementation in
this setting is the perception that discussions of sexuality should be private.
CONCLUSION: Implementation of evidence-based HIV interventions for young adult
African American women in church settings is feasible and needed. Building a
level of comfort in discussing matters of sexuality and adapting existing
evidence-based interventions to meet the needs of young women in church settings
is a viable approach for successful implementation.
PMID- 25139613
TI - Preparation and hydrosilylation activity of a molybdenum carbonyl complex that
features a pentadentate bis(imino)pyridine ligand.
AB - Attempts to prepare low-valent molybdenum complexes that feature a pentadentate
2,6-bis(imino)pyridine (or pyridine diimine, PDI) chelate allowed for the
isolation of two different products. Refluxing Mo(CO)6 with the pyridine
substituted PDI ligand, (PyEt)PDI, resulted in carbonyl ligand substitution and
formation of the respective bis(ligand) compound ((PyEt)PDI)2Mo (1). This complex
was investigated by single-crystal X-ray diffraction, and density functional
theory calculations indicated that 1 possesses a Mo(0) center that back-bonds
into the pi*-orbitals of the unreduced PDI ligands. Heating an equimolar solution
of Mo(CO)6 and the phosphine-substituted PDI ligand, (Ph2PPr)PDI, to 120 degrees
C allowed for the preparation of ((Ph2PPr)PDI)Mo(CO) (2), which is supported by a
kappa(5)-N,N,N,P,P-(Ph2PPr)PDI chelate. Notably, 1 and 2 have been found to
catalyze the hydrosilylation of benzaldehyde at 90 degrees C, and the
optimization of 2-catalyzed aldehyde hydrosilylation at this temperature afforded
turnover frequencies of up to 330 h(-1). Considering additional experimental
observations, the potential mechanism of 2-mediated carbonyl hydrosilylation is
discussed.
PMID- 25139614
TI - Low-grade albuminuria associated with brachial-ankle pulse wave velocity in young
adults with type 2 diabetes mellitus in China.
AB - BACKGROUND: Cardiovascular disease is prevalent in type 2 diabetics, and
microalbuminuria is associated with cardiovascular disease morbidity. We aimed to
investigate the potential association between low-grade albuminuria and arterial
stiffness in patients with type 2 diabetes. METHODS: Between 2009 and 2013, a
retrospective study was performed in 578 patients with type 2 diabetes (339 male
patients and 239 female patients) with normal urinary albumin-to-creatinine
ratios (ACRs; <30 mg/g) from Fuzhou, China. Patients were stratified into
tertiles based on urinary ACR levels (lowest tertile, urinary ACR < 4.8 mg/g;
highest tertile, urinary ACR >= 20.1 mg/g). Arterial stiffness was measured via
brachial-ankle pulse wave velocity. RESULTS: Brachial-ankle pulse wave velocity,
age, duration of diabetes, systolic blood pressure and pulse wave velocity
progressively increased across all urinary albumin-to-creatinine ratio tertiles
(p < 0.05). Patients in the second and the highest tertiles had significantly
elevated pulse wave velocity [114.6 mm/s (95% CI = 36.8-192.4) and 209.4 mm/s
(95% CI = 131.8-286.9)], p = 0.004 and 0.000] compared with those in the lowest
ACR tertile. The association between ACR and elevated pulse wave velocity still
persisted in patients younger than 65 years of age and those with diabetes <10
years, conferring 45 or 51% greater risk of elevated pulse wave velocity (OR =
1.451; 95% CI = 1.119-1.881; p = 0.005 or OR = 1.515; 95% CI = 1.167-1.966; p =
0.0018) with each ACR tertile increment. Each ACR tertile increment conferred
31.7% higher risk of increased pulse wave velocity (OR = 1.317; 95% CI = 1.004
1.729; p = 0.0468). CONCLUSIONS: Patients with type 2 diabetes with urinary
albumin excretion in the upper normal range were still at risk for target organ
damage. Low-grade albuminuria might be an early marker for the detection of
arterial stiffness in patients with type 2 diabetes, especially in younger
patients with type 2 diabetes with shorter durations of disease.
PMID- 25139615
TI - Expression and clinical significance of ATP-binding cassette transporter 1 in
serum and placental tissue in Chinese patients with preeclampsia.
AB - AIM: To investigate the expression and clinical significance of ATP-binding
cassette transporter 1 (ABCA1) in pregnant women with preeclampsia (PE). METHODS:
52 pregnant women with PE who were admitted for delivery were enrolled in the
study, while 30 normal pregnant inpatients were chosen as controls. Blood lipid
and serum ABCA1 concentrations were assayed by enzymatic analysis and ELISA,
respectively, and the expression of the ABCA1 gene and its encoded protein were
detected and quantified by RT-PCR and Western blotting. RESULTS: In the study
group, blood lipid levels were significantly higher than those in the control
group (p < 0.01), while the ABCA1 gene and its encoded protein expression in both
serum and placental tissue were lower than that of controls. These differences
were highly correlated with disease severity (p < 0.05). In PE patients, serum
ABCA1 concentration was positively correlated with ABCA1 protein expression in
placental tissue (r = 0.384, p < 0.01) and high-density lipoprotein level (r =
0.318, p < 0.05), but negatively correlated with low-density lipoprotein level (r
= -0.279, p < 0.05). CONCLUSION: In PE women, expression of ABCA1 was decreased,
suggesting that ABCA1 may play an important role in onset of PE by altering blood
lipid metabolism.
PMID- 25139616
TI - JLK1486, a N,N-[(8-hydroxyquinoline)methyl]-substituted benzylamine analogue,
inhibits melanoma proliferation and induces autophagy.
AB - OBJECTIVES: To investigate anti-proliferatory activity of a selected N,N-[(8
hydroxyquinoline)methyl]-substituted benzylamine (JLK1486) on melanoma cells and
to characterize its mechanism of cell population growth inhibition. MATERIALS AND
METHODS: In vitro cultures of B16F10 (mouse melanoma) cells were used as a model
to characterize anti-proliferatory activity of JLK1486 using MTT growth assay,
trypan blue viability assessment, cell cycle analysis, melanin production, beta
galactosidase and acridine orange staining. RESULTS: Proliferating B16F10 and
also MeWo (human melanoma) cells were strongly growth inhibited by JLK1486,
displaying IC50 values of 196 nm and 110 nm respectively. Anti-proliferatory
effects were independent of cell death and were characterized by a distinct
accumulation of cells in G0 /G1 phase. Tyrosinase activity and relative melanin
content remained unchanged indicating that the anti-proliferatory activity was
not due to phenotype differentiation. Although treated B16F10 cells stained
strongly positive for senescence marker beta-galactosidase, cells regained near
normal proliferatory activity after removal of JLK1486. Increased acridine orange
staining and presence of perinuclear vacuoles suggested induction of autophagy in
B16F10 cells. Furthermore, JLK1486 pre-treatment completely abolished melphalan
and antimycin A-induced apoptosis. CONCLUSION: JLK1486 provides a promising
chemical scaffold to develop new anti-melanoma drugs or combination therapies,
due to its potent inhibition of cell proliferation and induction of autophagy, at
pharmacologically relevant concentrations.
PMID- 25139617
TI - Effects of medical therapy or surgery on prostatic and bladder resistive indices
in patients with benign prostatic hyperplasia.
AB - INTRODUCTION: The effects of medical therapy or surgery on bladder and prostatic
resistive indices (RIs) in patients with lower urinary tract symptoms suggestive
of benign prostatic hyperplasia (LUTS/BPH) were evaluated in the present study.
PATIENTS AND METHODS: A total of 124 consecutive LUTS/BPH patients who were
candidates for medical therapy (alfuzosin 10 mg once daily, n=66) or surgery
(transurethral prostatectomy (TUR-P), n=58) were prospectively included. Baseline
assessment of patients was performed with the International Prostate Symptom
Score (IPSS), maximum urinary flow rate (Qmax), and prostatic and bladder RIs
measured using power Doppler imaging (PDI). All patients were re-evaluated 3
months after treatment measuring the same parameters. RESULTS: Following medical
therapy, mean IPSS (17.2+/-5.1 vs. 8.3+/-5.3, p=0.0001), postvoiding residual
(PVR) urine (80.0+/-80.5 vs. 40.3+/-38.6, p=0.0001), and prostatic RI (0.73+/-0.1
vs. 0.70+/-0.1, p=0.0001) were decreased, Qmax (13.7+/-4.2 vs. 16.9+/-5.9,
p=0.0001) was increased, and bladder RI remained unchanged (0.70+/-0.1 vs. 0.70+/
0.1, p=0.68). Mean IPSS (25.3+/-5.6 vs. 6.0+/-4.5, p=0.0001), PVR urine volume
(134.5+/-115.5 vs. 35.7+/-25.9, p=0.0001), and prostatic (0.78+/-0.1 vs. 0.67+/
0.04, p=0.0001) and bladder RIs (0.72+/-0.1 vs. 0.64+/-0.04, p=0.005) were
decreased, and Qmax (8.0+/-4.5 vs. 17.2+/-8.2, p=0.0001) was increased after TUR
P. CONCLUSIONS: Our results demonstrated that TUR-P decreased both prostatic and
bladder RIs, while alpha-blocker therapy did not change bladder RI in the early
posttreatment period in LUTS/BPH patients.
PMID- 25139618
TI - Does pain interfere with antidepressant depression treatment response and
remission in patients with depression and pain? An evidence-based structured
review.
AB - OBJECTIVE: The objective of this evidence-based structured review was to
determine if there is consistent evidence that pain interferes with achieving
antidepressant treatment response/remission of depression in patients with
depression and pain. METHODS: After exclusion criteria were applied, of 2,801
studies/reports, 17 studies addressed this question. They were sorted into the
four hypotheses outlined herein after. The percentage of studies supporting/not
supporting each hypothesis was calculated. The strength and consistency of the
evidence for each hypothesis were rated according to the Agency for Health Care
Research and Quality (AHRQ) guidelines. RESULTS: For the first hypothesis
(pretreatment pain levels will predict antidepressant depression response), nine
out of 10 (90%) studies supported it. For the second hypothesis (treatment
decreases in pain will be associated with antidepressant depression response),
two out of two (100%) studies supported it. For the third hypothesis
(pretreatment pain levels will predict antidepressant depression remission), six
out of six (100%) studies supported it. For the fourth hypothesis (treatment
decreases in pain will be associated with antidepressant depression remission),
five out of five (100%) supported it. Utilizing these percentages and AHRQ
guidelines, hypotheses 1, 3, and 4 received an A rating for consistency of
studies in supporting them. A consistency rating for hypothesis 2 could not be
generated because of too few studies in that group. CONCLUSIONS: Consistent
evidence was found that antidepressant treatment of depression in patients with
depression and pain can be negatively impacted by pain for achieving depression
response/remission. However, the overall number of studies supporting each
hypothesis was small. In addition, several potential confounders of the results
of this study were identified.
PMID- 25139620
TI - Downregulation of endogenous STAT3 augments tumoricidal activity of interleukin
15 activated dendritic cell against lymphoma and leukemia via TRAIL.
AB - Effector functions in tumor resistance by dendritic cells (DCs) are less well
characterized. In this study, we describe that the murine DCs upon stimulation
with recombinant IL-15 in vitro or in vivo, expresses TNF superfamily member
TRAIL which mediates cytotoxicity and growth inhibition against a murine lymphoma
called Dalton lymphoma (DL) via apoptosis. Presence of tumor lysate or intact
tumor cells significantly reduces the DC mediated tumoricidal effect, possibly
via masking and down-regulating TRAIL in DCs. The antitumor effect of DC derived
TRAIL was further augmented by deactivation of STAT3 in tumor cells by
cucurbitacin I, which makes it more susceptible to DC derived TRAIL Treatment of
tumor cells with cucurbitacin I upregulates TRAIL receptor expression in addition
to activation of caspases. Compared to naive DCs, DCs from tumor bearing mice are
significantly impaired in TRAIL expression and consequent antitumor functions
against DL which was partially restored by activation with IL-15 or LPS. Priming
with recombinant IL-15 prolongs the survival of tumor bearing mice treated with
cucurbitacin I. Naive peripheral blood DCs derived from chronic myeloid leukemia
(CML) patients have significant impairment in expression of TRAIL and consequent
tumoricidal properties against TRAIL sensitive lymphoma cell lines and primary
tumor cells compared to normal control.
PMID- 25139619
TI - Celastrol induces unfolded protein response-dependent cell death in head and neck
cancer.
AB - The survival rate for patients with oral squamous cell carcinoma (OSCC) has not
seen marked improvement in recent decades despite enhanced efforts in prevention
and the introduction of novel therapies. We have reported that pharmacological
exacerbation of the unfolded protein response (UPR) is an effective approach to
killing OSCC cells. The UPR is executed via distinct signaling cascades whereby
an initial attempt to restore folding homeostasis in the endoplasmic reticulum
during stress is complemented by an apoptotic response if the defect cannot be
resolved. To identify novel small molecules able to overwhelm the adaptive
capacity of the UPR in OSCC cells, we engineered a complementary cell-based assay
to screen a broad spectrum of chemical matter. Stably transfected CHO-K1 cells
that individually report (luciferase) on the PERK/eIF2alpha/ATF4/CHOP (apoptotic)
or the IRE1/XBP1 (adaptive) UPR pathways, were engineered [1]. The triterpenoids
dihydrocelastrol and celastrol were identified as potent inducers of UPR
signaling and cell death in a primary screen and confirmed in a panel of OSCC
cells and other cancer cell lines. Biochemical and genetic assays using OSCC
cells and modified murine embryonic fibroblasts demonstrated that intact PERK
eIF2-ATF4-CHOP signaling is required for pro-apoptotic UPR and OSCC death
following celastrol treatment.
PMID- 25139621
TI - Erg cooperates with TGF-beta to control mesenchymal differentiation.
AB - Transforming growth factor beta (TGF-beta) signaling plays an integral role in
skeletal development. Conditional deletion of the TGF-beta type II receptor
(Tgfbr2) from type II Collagen (Col2a) expressing cells results in defects in
development of the annulus fibrosus (AF) of the intervertebral disc (IVD). We
previously used microarray analysis to search for marker genes of AF as well as
transcription factors regulated by TGF-beta during AF development. The
transcription factor avian erythroblastosis virus E-26 (v-ets) oncogene related
(Erg) was identified in the microarray screen as a candidate regulator of AF
development. To study the effects of TGF-beta on AF differentiation and the role
of Erg in this process, we used mouse sclerotome grown in micromass cultures. At
0.5ng TGF-beta/ml, sclerotome cells started to express markers of AF. Regulation
of Erg by TGF-beta was confirmed in these cells. In addition, TGF-beta soaked
Affi-gel beads implanted into the axial skeleton of stage HH 25 chick embryos
showed that TGF-beta could induce expression of Erg mRNA in vivo. Next, an
adenovirus to over-express Erg in primary sclerotome micromass cultures was
generated. Over-expression of Erg led to a change in cell morphology and
inhibition of differentiation into hyaline cartilage as seen by reduced Alcian
blue staining and decreased Sox9 and c-Maf expression. Erg was not sufficient to
induce expression of AF markers and expression of Sca1, a marker of pluripotent
progenitor cells, was up-regulated in Erg expressing cells. When cells that
ectopically expressed Erg were treated with TGF-beta, enhanced expression of
specific differentiation markers was observed suggesting Erg can cooperate with
TGF-beta to regulate differentiation of the sclerotome. Furthermore, we showed
using co-immunopreciptiation that Erg and Smad3 bind to each other suggesting a
mechanism for their functional interaction.
PMID- 25139622
TI - An ADARPEF survey on respiratory management in pediatric anesthesia.
AB - BACKGROUND: There have been recent changes with regard to tools and concepts for
respiratory management of children undergoing general anesthesia. OBJECTIVES: To
determine the practice of pediatric anesthetists concerning: preoxygenation,
breathing systems, ventilation modes, anesthetic agent and airway device,
strategies for a general anaesthetic of less than 30 min using spontaneous
respiration, and opinion about technical aspects of ventilation. METHODS: Online
questionnaire sent by e-mail to all the anesthetists registered on the mailing
list of the French-speaking Pediatric Anesthetists and Intensivists Association
(ADARPEF). RESULTS: 232 questionnaires (46%) were returned. More than 25% of
anesthetists surveyed declared that they do not perform preoxygenation before
induction for children <15 years old, apart from neonates and clinical specific
situations. When performed, <65% chose a FiO2 higher than 80%. Inhalational
induction with sevoflurane is the preferred mode of induction set at 6% or 8%,
respectively, 69% [62-75] vs 25% [18-31]. For induction, the circle system was
the most popular circuit used in all ages. The accessory breathing system
Mapleson B type-was predominantly used for neonates (44% [37-54]). For
maintenance of an anesthesia lasting <30 min in spontaneous breathing, the use of
laryngeal mask increased with age, and the endotracheal tube was reserved for
neonates (40% [33-48]). Pressure support ventilation was rarely used from the
beginning of induction but was widely used for maintenance, whatever the age
group. Results differed according to the type of institution. CONCLUSION:
Ventilation management depends on the age and institutions in terms of circuit,
airway device or ventilation mode, and specific differences exist for neonates.
PMID- 25139624
TI - In vivo correlation between axon diameter and conduction velocity in the human
brain.
AB - The understanding of the relationship between structure and function has always
characterized biology in general and neurobiology in particular. One such
fundamental relationship is that between axon diameter and the axon's conduction
velocity (ACV). Measurement of these neuronal properties, however, requires
invasive procedures that preclude direct elucidation of this relationship in
vivo. Here we demonstrate that diffusion-based MRI is sensitive to the fine
microstructural elements of brain wiring and can be used to quantify axon
diameter in vivo. Moreover, we demonstrate the in vivo correlation between the
diameter of an axon and its conduction velocity in the human brain. Using
AxCaliber, a novel magnetic resonance imaging technique that enables us to
estimate in vivo axon diameter distribution (ADD) and by measuring the
interhemispheric transfer time (IHTT) by electroencephalography, we found
significant linear correlation, across a cohort of subjects, between brain
microstructure morphology (ADD) and its physiology (ACV) in the tactile and
visual sensory domains. The ability to make a quantitative assessment of a
fundamental physiological property in the human brain from in vivo measurements
of ADD may shed new light on neurological processes occurring in neuroplasticity
as well as in neurological disorders and neurodegenerative diseases.
PMID- 25139623
TI - Cerebellar control of gait and interlimb coordination.
AB - Synaptic and intrinsic processing in Purkinje cells, interneurons and granule
cells of the cerebellar cortex have been shown to underlie various relatively
simple, single-joint, reflex types of motor learning, including eyeblink
conditioning and adaptation of the vestibulo-ocular reflex. However, to what
extent these processes contribute to more complex, multi-joint motor behaviors,
such as locomotion performance and adaptation during obstacle crossing, is not
well understood. Here, we investigated these functions using the Erasmus Ladder
in cell-specific mouse mutant lines that suffer from impaired Purkinje cell
output (Pcd), Purkinje cell potentiation (L7-Pp2b), molecular layer interneuron
output (L7-Deltagamma2), and granule cell output (alpha6-Cacna1a). We found that
locomotion performance was severely impaired with small steps and long step times
in Pcd and L7-Pp2b mice, whereas it was mildly altered in L7-Deltagamma2 and not
significantly affected in alpha6-Cacna1a mice. Locomotion adaptation triggered by
pairing obstacle appearances with preceding tones at fixed time intervals was
impaired in all four mouse lines, in that they all showed inaccurate and
inconsistent adaptive walking patterns. Furthermore, all mutants exhibited
altered front-hind and left-right interlimb coordination during both performance
and adaptation, and inconsistent walking stepping patterns while crossing
obstacles. Instead, motivation and avoidance behavior were not compromised in any
of the mutants during the Erasmus Ladder task. Our findings indicate that cell
type-specific abnormalities in cerebellar microcircuitry can translate into
pronounced impairments in locomotion performance and adaptation as well as
interlimb coordination, highlighting the general role of the cerebellar cortex in
spatiotemporal control of complex multi-joint movements.
PMID- 25139625
TI - Endogenous-cue prospective memory involving incremental updating of working
memory: an fMRI study.
AB - INTRODUCTION: Prospective memory paradigms are conventionally classified on the
basis of event-, time-, or activity-based intention retrieval. In the vast
majority of such paradigms, intention retrieval is provoked by some kind of
external event. However, prospective memory retrieval cues that prompt intention
retrieval in everyday life are commonly endogenous, i.e., linked to a specific
imagined retrieval context. We describe herein a novel prospective memory
paradigm wherein the endogenous cue is generated by incremental updating of
working memory, and investigated the hemodynamic correlates of this task.
METHODS: Eighteen healthy adult volunteers underwent functional magnetic
resonance imaging while they performed a prospective memory task where the
delayed intention was triggered by an endogenous cue generated by incremental
updating of working memory. Working memory and ongoing task control conditions
were also administered. RESULTS: The 'endogenous-cue prospective memory
condition' with incremental working memory updating was associated with maximum
activations in the right rostral prefrontal cortex, and additional activations in
the brain regions that constitute the bilateral fronto-parietal network, central
and dorsal salience networks as well as cerebellum. In the working memory control
condition, maximal activations were noted in the left dorsal anterior insula.
CONCLUSIONS: Activation of the bilateral dorsal anterior insula, a component of
the central salience network, was found to be unique to this 'endogenous-cue
prospective memory task' in comparison to previously reported exogenous- and
endogenous-cue prospective memory tasks without incremental working memory
updating. Thus, the findings of the present study highlight the important role
played by the dorsal anterior insula in incremental working memory updating that
is integral to our endogenous-cue prospective memory task.
PMID- 25139626
TI - Erratum to: Glutamate receptors of the delta family are widely expressed in the
adult brain.
PMID- 25139627
TI - [Care of geriatric otorhinolaryngology patients].
PMID- 25139628
TI - Standard of care and future pharmacological treatment options for malignant
glioma: an urgent need for screening and identification of novel tumor-specific
antigens.
AB - INTRODUCTION: Malignant gliomas (MGs) represent the most common primary brain
tumors in adults, the most deadly of which is grade IV glioblastoma. Patients
with glioblastoma undergoing current standard-of-care therapy have a median
survival of 12 - 15 months. AREAS COVERED: Over the past 25 years, there have
been modest advancements in the treatment of MGs. Assessment of therapeutic
responses has continued to evolve to account for the increasing number of agents
being tested in the clinic. Currently approved therapies for primary tumors have
been extended for use in the setting of recurrent disease with modest efficacy.
Agents initially approved for recurrent gliomas have begun to demonstrate
efficacy against de novo tumors but will ultimately need to be evaluated in
future studies for scheduling, timing and dosing relative to chemotherapy. EXPERT
OPINION: Screening and identification of tumor-specific mutations is critical for
the advancement of effective therapy that is both safe and precise for the
patient. Two unique antigens found in glioblastoma are currently being employed
as targets for immunotherapeutic vaccines, one of which has advanced to Phase III
testing. Whole genome sequencing of MGs has yielded two other novel mutations
that offer great promise for the development of molecular inhibitors.
PMID- 25139629
TI - Mandarin version of the Leeds Dyspepsia Questionnaire: A valid instrument for
assessing symptoms in Asians.
AB - OBJECTIVE: To develop and validate a Mandarin version of the Leeds Dyspepsia
Questionnaire (M-LDQ) in Asian patients with dyspepsia. METHODS: The M-LDQ was
developed according to standardized methods. The validity, internal consistency,
test-retest reliability and responsiveness of the instrument were evaluated in
both primary and secondary care patients. RESULTS: A total of 184 patients (mean
age 54.0 +/- 15.8 years, of whom 59% were women and 72.3% of whom had at least
secondary level education) were recruited between August 2012 and March 2013,
from both primary (n = 100) and secondary care clinics (n = 84). Both the
internal consistency of all components of the M-LDQ (Cronbach's alpha 0.79) and
test-retest reliability (Spearman's correlation coefficient 0.78) were good. The
M-LDQ was valid in diagnosing dyspepsia in primary care (area under the receiver
operating characteristics curve 0.84) and was able to discriminate between
secondary and primary care patients (median cumulative LDQ score 13.0 vs 3.0, P <
0.0001). Among eight patients with organic dyspepsia, the median M-LDQ score
reduced significantly from 21.0 (pretreatment) to 9.5 (4 weeks post-treatment) (P
< 0.0001). CONCLUSION: The M-LDQ is a valid and responsive instrument for
assessing ethnic Chinese adults with dyspepsia.
PMID- 25139630
TI - Outcomes in acute heart failure: 30-day readmission versus death.
AB - For patients hospitalized with acute heart failure, health policy initiatives in
the USA have drawn attention to 30-day mortality and readmission. Confusion
around definitions, populations, and thus reported rates for these two outcomes
is common. Among Medicare fee-for-service patients hospitalized with heart
failure, all-cause mortality 30 days from the time of admission is 11.7 % and all
cause unplanned readmission 30 days from discharge is 23.0 %. Rates for Medicaid
and commercially insured patients are lower. Mortality rates have been relatively
stable, while readmission rates increased under the Diagnosis Related Group
payment system then began decreasing under the Hospital Readmission Reductions
Program. Risk models are reasonable at predicting mortality, whereas readmission
has been harder to anticipate. The use of risk-standardized hospital rates as
performance measures has generated considerable debate. Future work should
clarify the interaction between the two measures, the optimal time window and
factors influencing rates and trends-including socioeconomic status.
PMID- 25139631
TI - Patterns and determinants of new first-line antihyperglycaemic drug use in
patients with type 2 diabetes mellitus.
AB - AIMS: We evaluated the patterns and determinants that influence the selection,
timing and duration of first-line antihyperglycaemic drug (AHD) treatment in
patients with type 2 diabetes in Germany, focusing specifically on treatment
naive AHD initiators. METHODS: Pharmacy dispensing claims data were linked with a
cohort of patients newly enrolled in a German Disease Management Program for type
2 diabetes (DMP-DM2) between 2003 and 2009. We examined uptake of first-line
pharmacotherapy in previously unmedicated patients and identified predictors of
receiving AHD therapy in general and metformin in particular using multivariable
regression analyses. RESULTS: There were 27,138 unmedicated patients with type 2
diabetes and 47.0% of them were started on AHD treatment within 5 years after
enrollment. Initial severity of diabetes was the major predictor of receiving
first-line pharmacotherapy. Metformin accounted for 63% of newly prescribed AHD
in 2003 and more than 80% in 2009 while sulfonylureas accounted for only 10%.
Initiating metformin as first-line AHD was associated with younger age, higher
BMI, lower HbA1c, and shorter diabetes duration (multivariate p<0.001 for all).
Therapy switch or step-up was less frequent among metformin initiators than
sulfonylurea initiators. CONCLUSIONS: The majority of patients were not started
on AHD therapy within 5 years after enrollment. In line with recent therapy
guidelines, current first-line antihyperglycaemic treatment was increasingly
based on metformin. AHD initiators started on sulfonylurea were generally more
advanced in their disease and were started later on primary pharmacotherapy.
PMID- 25139632
TI - Predictors of diabetes foot complications among patients with diabetes in Saudi
Arabia.
AB - AIMS: To identify risk factors and clinical biomarkers of prevalent diabetes foot
complications, including foot ulcers, gangrene and amputations among patients
with diabetes in Jeddah, Saudi Arabia. METHODS: 598 diabetes patients from Jeddah
participated in the current study. Patients were considered to have diabetes foot
complications if they reported diagnosis of foot ulcers or gangrene or
amputations in a questionnaire administered by a physician and confirmed by
clinical exams. Information on socio-demographic and lifestyle variables was self
reported by patients, and several clinical markers were assessed following
standard procedures. RESULTS: The prevalence of diabetes foot complications in
this population was 11.4%. In the multivariable model without adjustment for PAD
(peripheral artery disease) and DPN (diabetes peripheral neuropathy), non-Saudi
nationality, longer diabetes duration and insulin use was significantly
associated with higher diabetes foot complications prevalence. Each 1g/L increase
of hemoglobin was associated with 2.8% lower prevalence of diabetes foot
complications. In the multivariable model adjusting for PAD and DPN, the
previously observed associations except for nationality were no longer
significant. Patients with both DPN and PAD had 9.73 times the odds of diabetes
foot complications compared to the patients with neither condition. CONCLUSION:
In this population, longer diabetes duration, insulin use, lower hemoglobin
levels and non-Saudi nationality were associated with higher prevalence of foot
complications. These associations were largely explained by the presence of DPN
and PAD except for non-Saudi nationality. Diabetes patients with both DPN and PAD
had nearly 10-fold increased risk of foot complications than those with neither
condition.
PMID- 25139633
TI - Pulmonary vascular tone is dependent on the central modulation of sympathetic
nerve activity following chronic intermittent hypoxia.
AB - Chronic intermittent hypoxia (IH) provokes a centrally mediated increase in
sympathetic nerve activity (SNA). Although this sympathetic hyperexcitation has
been linked to systemic hypertension, its effect on the pulmonary vasculature is
unclear. This study aimed to assess IH-mediated sympathetic excitation in
modulating pulmonary vasculature tone, particularly acute hypoxia vasoconstrictor
response (HPV), and the central beta-adrenergic signaling pathway for
facilitating the increase in SNA. Sprague-Dawley rats were exposed to IH (cycle
of 4% O2 for 90 s/air for 90 s) for 8 h/day for 6 weeks. Subsequently, rats were
anesthetized and either pulmonary SNA was recorded (electrophysiology), or the
pulmonary vasculature was visualized using microangiography. Pulmonary
sympathetic and vascular responses to acute hypoxia were assessed before and
after central beta1-adrenergic receptor blockade (Metoprolol, 200 nmol i.c.v.).
Chronic IH increased baseline SNA (110% increase), and exacerbated the
sympathetic response to acute hypoxia. Moreover, the magnitude of HPV in IH rats
was blunted compared to control rats (e.g., 10 and 20% vasoconstriction,
respectively). In only the IH rats, beta1-receptor blockade with metoprolol
attenuated the hypoxia-induced increase in pSNA and exacerbated the magnitude of
acute HPV, so that both sympathetic and HPV responses were similar to that of
control rats. Interestingly, the expression of beta1-receptors within the
brainstem was similar between both control and IH rats. These results suggest
that the centrally mediated increase in SNA following IH acts to blunt the local
vasoconstrictor effect of acute hypoxia, which reflects an inherent difference
between vasodilator and vasoconstrictor actions of SNA in pulmonary and systemic
circulations.
PMID- 25139634
TI - Metabolomic analysis of amino acid and fat metabolism in rats with L-tryptophan
supplementation.
AB - Tryptophan (TRP) is an important precursor for several neurotransmitters and
metabolic regulators, which play a vital role in regulating nutrient metabolism.
The purpose of this study was to investigate the effects of tryptophan
supplementation on the biochemical profiles, intestinal structure, liver
structure and serum metabolome in rats. Rats received daily intragastric
administration of either tryptophan at doses of 200 mg/kg body weight per day or
saline (control group) for 7 days. TRP supplementation had a tendency to decrease
the body weight of rats (P > 0.05). The levels of urea and CHO in serum were
decreased in the TRP-supplemented group rats compared with control group rats (P
< 0.05). TRP supplementation increased the villus height and the ratio of villus
height to crypt depth in the jejunum compared to control group rats (P < 0.05).
Metabolic effects of tryptophan supplementation include: (1) increases in the
serum concentrations of lysine, glycine, alanine, glutamate, glutamine,
citrulline, methionine, tyrosine, 1-methylhistidine, and albumin, and decreases
in the concentrations of serum branched-chain amino acid (isoleucine, valine and
leucine); (2) decreases in the serum concentrations of formate and nitrogenous
products (trimethylamine, TMAO, methylamine and dimethylamine), and in the
contraction of trimethylamine in feces; (3) decreases in serum levels of lipids,
low density lipoprotein, very low density lipoprotein, together with the elevated
ratio of acetoacetate to beta-hydroxybutyrate. The results indicate that
tryptophan supplementation reduced the catabolism of dietary amino acids and
promoted protein synthesis in rats, promoted the oxidation of fatty acid and
reduced fat deposition in the body of rats.
PMID- 25139635
TI - A review of the economic tools for assessing new medical devices.
AB - Whereas the economic evaluation of pharmaceuticals is an established practice
within international health technology assessment (HTA) and is often produced
with the support of comprehensive methodological guidance, the equivalent
procedure for medical devices is less developed. Medical devices, including
diagnostic products, are a rapidly growing market in healthcare, with over 10,000
medical technology patent applications filed in Europe in 2012-nearly double the
number filed for pharmaceuticals. This increase in the market place, in
combination with the limited, or constricting, budgets that healthcare decision
makers face, has led to a greater level of examination with respect to the
economic evaluation of medical devices. However, methodological questions that
arise due to the unique characteristics of medical devices have yet to be
addressed fully. This review of journal publications and HTA guidance identified
these characteristics and the challenges they may subsequently pose from an
economic evaluation perspective. These unique features of devices can be grouped
into four categories: (1) data quality issues; (2) learning curve; (3) measuring
long-term outcomes from diagnostic devices; and (4) wider impact from
organisational change. We review the current evaluation toolbox available to
researchers and explore potential future approaches to improve the economic
evaluation of medical devices.
PMID- 25139636
TI - Autoimmune pulmonary alveolar proteinosis co-existing with breast cancer: a case
report.
AB - INTRODUCTION: Pulmonary alveolar proteinosis is a rare pulmonary disease
characterized by excessive alveolar accumulation of surfactant due to defective
alveolar clearance by macrophages. There are only a few published case reports of
pulmonary alveolar proteinosis occurring in association with solid cancers. To
the best of our knowledge, there are no previously reported cases of pulmonary
alveolar proteinosis associated with breast cancer. CASE PRESENTATION: A 48-year
old Asian woman, a nonsmoker, presented to our institution with a right breast
mass. Biopsy examination of the lesion revealed scirrhous carcinoma. A chest
computed tomography scan for metastases showed abnormal shadows in both upper
lung fields. As a result of flexible fiberscopic bronchoscopy, this patient was
diagnosed as having pulmonary alveolar proteinosis. This case was categorized as
autoimmune pulmonary alveolar proteinosis due to the positive anti-granulocyte
macrophage colony-stimulating factor antibody. Pulmonary alveolar proteinosis
decreased gradually after mastectomy. CONCLUSIONS: The present case involved the
coincident occurrence of autoimmune pulmonary alveolar proteinosis with breast
cancer; breast cancer may be a factor during pulmonary alveolar proteinosis
development.
PMID- 25139638
TI - Role of dietary fats in the prevention and treatment of the metabolic syndrome.
AB - A symposium on the health significance of dietary fat in the prevention and
treatment of the metabolic syndrome (MetS) was held at the 20th International
Congress of Nutrition in Granada, Spain, on September 19, 2013. Four nutrition
experts addressed the topics of dietary fat and obesity, effects of dietary fat
quality in obesity and insulin resistance, influence of early nutrition on the
later risk of MetS and the relative merits of high- or low-fat diets in
counteracting MetS. Participants agreed that preventing weight gain and achieving
weight loss in overweight and obese patients were key strategies for reducing
MetS. Both low-fat and low-carbohydrate diets are associated with weight loss,
but adherence to the diet is the most important factor in achieving success.
Avoidance of high saturated fats contributes to lower health risks among obese,
MetS and diabetic patients. Further, healthy maternal weight at conception and in
pregnancy is more important that weight gain during pregnancy for reducing the
risk of obesity in the offspring. The effects of different polyunsaturated fatty
acids on MetS and weight loss require clarification.
PMID- 25139639
TI - TACE performed in patients with a single nodule of hepatocellular carcinoma.
AB - BACKGROUND: Patients with single hepatocellular carcinoma (HCC) usually undergo
transarterial chemoembolization (TACE) if they are not candidates for curative
surgical or ablative therapy. The primary aim of the study was to assess the
overall survival and clinical determinants of survival in patients with single
HCC who underwent TACE. The secondary aims were tumor response, local and distant
recurrence rates, time to recurrence and the impact of TACE on liver function.
METHODS: The outcomes of 148 consecutive patients with single HCC who underwent
TACE from January 2004 to December 2009 were retrospectively analyzed. RESULTS:
Complete response (CR) was observed in 95/148 (64%) patients and a partial
response (PR) in 39 (26%) patients. The recurrence rate was 27%, 42% and 65% at
6, 12 and 24 months, respectively. The day after TACE, 56 (38%) patients had a
Child-Pugh increase >= 1 and 93 (63%) had a MELD increase >= 1. Median survival
was 36.0 months with 1-, 3- and 5-year survival rates of 85%, 50% and 26%,
respectively. Bland portal thrombosis was not seen to have any impact at
univariate survival analysis; however, a slight impairment of PS (PS-1) in small
tumors had some, although minor, impact on prognosis. Factors associated with
shorter survival at multivariate analysis were tumor >5 cm, absence of CR,
ascites, alpha-fetoprotein (AFP) >= 14.5 ng/mL and a MELD increase >= 1.
CONCLUSIONS: Transarterial chemoembolization is a valid treatment option in
patients with single HCC not suitable for curative treatment. Bland PVT has no
major impact on survival and a slight impairment of PS attributable to cirrhosis
in patients within the Milan criteria should not preclude the use of TACE.
PMID- 25139640
TI - First you find the "criminals" in research fraud.
PMID- 25139641
TI - Triphasic and epithelioid minimal fat renal angiomyolipoma and clear cell renal
cell carcinoma: qualitative and quantitative CEUS characteristics and
distinguishing features.
AB - PURPOSE: To determine the contrast-enhanced ultrasonography (CEUS)
characteristics of minimal fat renal angiomyolipoma (AML) (triphasic and
epithelioid) and compare them to each other and to clear cell renal cell
carcinoma (ccRCC) to explore their differential diagnostic clue. METHODS:
Qualitative and quantitative CEUS analyses were retrospectively conducted for
epithelioid renal AMLs (EAMLs) (n = 15), triphasic minimal fat AMLs (TAMLs) (n =
25), and ccRCCs (n = 113). Enhancement patterns and features with CEUS were
qualitatively evaluated. As for the quantitative parameters, rise times (RT),
time to peak (TTP), and tumor-to-cortex enhancement ratio (TOC ratio) were
compared among these renal tumor histotypes. RESULTS: No significant differences
were detected on conventional ultrasound in the three histotypes of renal tumor.
On qualitative CEUS analysis, centripetal enhancement in cortical phase (73.3% in
EAMLs, 84.0% in TAMLs vs. 18.6% in ccRCCs, p < 0.001 for both), homogeneous peak
enhancement (100.0% in both EAMLs and TAMLs vs. 43.4% in ccRCCs, p < 0.001 for
both), and iso-enhancement in parenchyma phase (53.3% in AMLs, 52.0% in TAMLs vs.
26.5% in ccRCCs, p = 0.034 and 0.013, respectively) were valuable traits for
differentiating EAMLs and TAMLs from ccRCCs. Furthermore, with quantitative
analysis, RT and TTP were much shorter in ccRCCs than those in EAMLs and TAMLs.
However, all these qualitative and quantitative characteristics made no
significant difference between EAMLs and TAMLs. In the differential diagnosis of
EAMLs from TAMLs, pseudocapsule sign was valuable (40.0% in EAMLs vs. 0.0% in
TAMLs, p < 0.001), and TOC ratio was much higher in EAMLs (166.01 +/- 64.47%)
than that in TAMLs (93.74 +/- 46.56%)(p < 0.001), though they did make overlaps
with ccRCCs. With either heterogeneous peak enhancement or the presence of
pseudocapsule or TOC ratio >97.34% as the criteria to differentiate ccRCCs and
EAMLs from TAMLs, the sensitivity and specificity were 80.0% and 87.5%,
respectively. CONCLUSIONS: Qualitative and quantitative CEUS analyses are helpful
in the differential diagnosis of ccRCCs, EAMLs, and TAMLs.
PMID- 25139642
TI - The role of pure iterative reconstruction in conventional dose CT enterography.
AB - PURPOSE: Pure iterative reconstruction (Pure IR) has been proposed as a solution
to improve diagnostic quality of low dose CT images. We assess the performance of
model based iterative reconstruction (MBIR) in improving conventional dose CT
enterography (CTE) images. METHODS: 43 Crohn's patients (27 female) (38.5 +/-
12.98 years) referred for CTE were included. Images were reconstructed with pure
IR (MBIR, General Electric Healthcare) in addition to standard department
protocol (reconstructed with hybrid iterative reconstruction (Hybrid IR) [60%
filtered back projection/40% adaptive statistical IR (General Electric
Healthcare)]. Image quality was assessed objectively and subjectively at 6
anatomical levels. Clinical interpretation was undertaken in consensus by 2
blinded radiologists along with 2 non-blinded readers ('gold standard'). Results
were analyzed using Statistical Package for Social Scientists. RESULTS: Mean
effective radiation dose was 6.05 +/- 2.84 mSv (size specific dose estimates 9.25
+/- 2.9 mGy). Objective and subjective assessment yielded 6106 data points. Pure
IR images significantly outperformed those using standard reconstruction
techniques across all subjective (p < 0.001 for all comparisons) (noise, contrast
resolution, spatial resolution, streak artifact, axial diagnostic acceptability,
coronal diagnostic acceptability) and objective (p < 0.004) (noise, signal-to
noise ratio) parameters. Clinical reads of the pure IR images agreed more closely
with the gold standard reads than the hybrid IR image reads in terms of overall
Crohn's activity grade (kappa = 0.630, 0.308) and detection of acute
complications (kappa = 1.0, 0.896). Results were comparable for bowel wall
disease severity assessment (kappa = 0.523, 0.593). CONCLUSIONS: Pure IR
considerably improves image quality of conventional dose CTE images and therefore
its use should be expanded beyond low dose protocols to improving image quality
at conventional dose CT imaging.
PMID- 25139643
TI - Multimodality imaging of common and uncommon peritoneal diseases: a review for
radiologists.
AB - Peritoneal disease can be caused by a wide spectrum of pathologies. While
peritoneal disease is usually caused by primary or secondary malignancies, benign
diseases can occur and mimic malignancies. This article begins with an overview
of peritoneal embryology and anatomy followed by a detailed description of the
multimodality imaging appearance of peritoneal diseases. Common diseases include
peritoneal carcinomatosis, pseudomyxoma peritonei, lymphomatosis, sarcomatosis,
and tuberculous peritonitis. The uncommon diseases which cause peritoneal disease
include desmoid fibromatosis, desmoplastic small round cell tumor, malignant
mesothelioma, well-differentiated mesothelioma, multicystic mesothelioma,
papillary serous carcinoma, leiomyomatosis, extramedullary hematopoiesis,
inflammatory pseudotumor and amyloidosis. This manuscript will help the
radiologist become familiar with the different peritoneal spaces, pathways of
spread, multimodality imaging appearance and differential diagnoses of peritoneal
diseases in order to report the essential information for surgeons and
oncologists to plan treatment.
PMID- 25139644
TI - Far-field atrial sensing by the left ventricular channel of a biventricular
device.
AB - BACKGROUND: The left ventricular (LV) channel of Biotronik biventricular devices
used for cardiac resynchronization therapy (CRT) is designed with the capability
of sensing via the LV lead. Therefore a displaced LV lead in a coronary vein
could sense far-field atrial signals and interfere with CRT. METHODS: The
Biotronik troubleshooting archives containing data of approximately 700
transvenous CRT-D cases (D = defibrillator) were examined for atrial far-field
sensing by the LV channel. We selected three cases from the archives to
demonstrate the typical features of LV sensing of far-field atrial activity.
RESULTS: We found 3 typical cases of far-field atrial sensing by the LV channel.
The LV lead was displaced in 2 cases and possibly in the third patient. Two cases
exhibited short intervals between LV sensed events (LVs-LVs = 207-218 ms), a
finding typical of this form of far-field atrial sensing by an LV lead. In the
third case, short LVs-LVs intervals were not observed because spontaneous LV
activation failed to generate an LVs marker (corresponding with the terminal LVs
marker in a short LVs-LVs interval). LV activity was unsensed during the blanking
period of the LV upper rate interval initiated by the first LVs that actually
generated by far-field oversensing. This response was also observed
intermittently in a patient who presented with short LVs-LVs intervals.
CONCLUSIONS: Far-field atrial oversensing by the LV channel of a CRT-D device
occurs mostly with LV lead displacement. The diagnosis is important because it
interferes with the delivery of therapeutic CRT but it is not life-threatening.
Oversensing can be easily corrected by simple reprogramming of the device or LV
lead repositioning if there is high LV pacing threshold.
PMID- 25139645
TI - Synthesis and properties of single domain sphere-shaped barium hexa-ferrite nano
powders via an ultrasonic-assisted co-precipitation route.
AB - To synthesize high quality barium hexa-ferrite nano powders, an ultrasonic
assisted co-precipitation method has been used and the influences of the
ultrasonic technique on the particle morphologies and magnetic properties of the
synthesized barium hexa-ferrite nano powders have been investigated. The results
indicated that the introduction of ultrasonic energy into the co-precipitation
process promoted the composition homogeneities of the co-precipitated precursors,
minished their particle sizes, and exerted the additional surface barriers
between the particles, which influenced both the phase formation and particle
growth-up processes during the subsequent heating treatment and altered the
particle sizes, size distributions and particle shapes of the final synthesized
powders. The average particle sizes of the synthesized nano powders dramatically
decreased from 210 nm to about 100 nm as the inputting ultrasonic power
increased, while the size distribution became increasingly uniform except for a
few of large particles existed as the inputting power approached to a high value.
The magnetization at 1.4 T of the as-synthesized barium hexa-ferrite dramatically
increased and approached to the highest value of 57.9 emu/g due to the
elimination of multi-domain particles, the alleviation of particle adhesion and
the evolution of particle shape from flake to quasi-sphere as well as the uniform
particle size distribution as the ultrasonic assistance was employed, and
slightly decreased because of the coarsening in particle sizes.
PMID- 25139646
TI - Stable carbon isotope ratio profiling of illicit testosterone preparations-
domestic and international seizures.
AB - Gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) is now
established as a robust and mature analytical technique for the doping control of
endogenous anabolic androgenic steroids in human sport. It relies on the
assumption that the carbon isotope ratios of naturally produced steroids are
significantly different to synthetically manufactured testosterone or
testosterone prohormones used in commercial medical or dietary supplement
products. Recent publications in this journal have highlighted the existence of
black market testosterone preparations with carbon isotope ratios within the
range reported for endogenous steroids (i.e. delta(13) C >= -25.8 0/00). In this
study, we set out to profile domestic and international law enforcement seizures
of illicit testosterone products to monitor the prevalence of 'enriched'
substrates--which if administered to human subjects would be considered
problematic for the use of current GC-C-IRMS methodologies for the doping control
of testosterone in sport. The distribution of delta(13) C values for this illicit
testosterone sample population (n = 283) ranged from -23.4 0/00 to -32.9 0/00
with mean and median of -28.6 0/00--comparable to previous work. However, only 13
out of 283 testosterone samples (4.6 %) were found to display delta(13) C values
>= -25.8 0/00, confirming that in the vast majority of cases of illicit
testosterone administration, current GC-C-IRMS doping control procedures would be
capable of confirming misuse.
PMID- 25139647
TI - Electroconvulsive stimulation, but not chronic restraint stress, causes
structural alterations in adult rat hippocampus--a stereological study.
AB - The neurobiological mechanisms underlying depression are not fully understood.
Only a few previous studies have used validated stereological methods to test how
stress and animal paradigms of depression affect adult hippocampal neurogenesis
and whether antidepressant therapy can counteract possible changes in an animal
model. Thus, in this study we applied methods that are state of the art in regard
to stereological cell counting methods. Using a validated rat model of depression
in combination with a clinically relevant schedule of electroconvulsive
stimulation, we estimated the total number of newly formed neurons in the
hippocampal subgranular zone. Also estimated were the total number of neurons and
the volume of the granule cell layer in adult rats subjected to chronic restraint
stress and electroconvulsive stimulation either alone or in combination. We found
that chronic restraint stress induces depression-like behavior, without
significantly changing neurogenesis, the total number of neurons or the volume of
the hippocampus. Further, electroconvulsive stimulation prevents stress-induced
depression-like behavior and increases neurogenesis. The total number of neurons
and the granule cell layer volume was not affected by electroconvulsive
stimulation.
PMID- 25139648
TI - [The future of the CT scan; will CT replace conventional radiography?].
AB - The number of CT scans being made has increased over the past few years. New CT
technology has been developed to reduce the individual patient radiation dose. By
using this technology it is possible to make CT scans with a radiation dose
approaching conventional X-rays, which means that in the future radiation dose
may not form a limitation to making CT scans. The indication for CT scans will
broaden, and low-dose CT scans will increasingly replace conventional
radiography.
PMID- 25139649
TI - [Delusional infestation, a therapeutic challenge].
AB - Delusional infestation, formally known as delusional parasitosis, poses a
therapeutic challenge. This article provides tools to engage these patients with
psychiatric treatment. We present two men aged 49 and 48 who saw the
dermatologist with skin symptoms due to primary and secondary delusional
infestation, respectively. Despite their anosognosia, both patients were
successfully treated with antipsychotics thanks to the collaboration between
dermatology and psychiatry. To increase the acceptability of treatment with
antipsychotics, emphasis should be placed on their antipruritic properties and
the effect on degree of preoccupation with the infection rather than their
antipsychotic properties. Follow-up is important, as patients mostly do not
attribute their recovery to antipsychotics and the risk of recurrence is high
after cessation of antipsychotic medication.
PMID- 25139650
TI - [Risks of intrahepatic cholestasis of pregnancy].
AB - Intrahepatic cholestasis of pregnancy (ICP) is defined as pruritus during
pregnancy in the absence of primary skin lesions, combined with an increase in
serum total bile salts and/or abnormal serum liver tests. This article provides
an insight into the diagnostic and therapeutic considerations by presenting two
cases. ICP usually presents around 34 weeks of gestation, but can be present
early in pregnancy as described in a 32-year-old patient pregnant after in-vitro
fertilization. DNA analysis showed a mutation in the ABCB4 gene, causing MDR3
deficiency. Ursodeoxycholic acid treatment seems to alleviate maternal pruritus
and possibly reduces perinatal risks related to the severe form of ICP, defined
as fasted serum bile salt levels of >= 40 MUmol/l at any point during the
pregnancy. Short-term rifampicin treatment can be considered in patients with
persistent pruritus. Induction of labour is advised only after 37 weeks of
gestation in patients with severe ICP.
PMID- 25139651
TI - [Ethnic differences in uptake of professional maternity care assistance].
AB - OBJECTIVE: To examine the ethnic differences in the uptake of professional
maternity care assistance (MCA) in the Netherlands, and the factors that may
explain these differences. Additionally the effect of MCA on health risk
behaviour around infants is examined. DESIGN: Questionnaire survey. METHOD:
Questionnaire data from 3967 mothers from the ABCD study (Amsterdam Born Children
and their Development) included during pregnancy in 2003-2004, were used. We
examined the explanatory role of ethnicity, age, socioeconomic status, mastery of
the Dutch language, parity, housing situation and place of giving birth on MCA
uptake, and the effect of MCA uptake on health risk behaviour around infants,
such as smoking indoors, infant sleep behaviour, infant nutrition, and response
to infant crying. RESULTS: Mothers of non-Western origin less often used MCA than
Dutch mothers (Ghanaian: 70%; Turkish: 75%; Moroccan: 79%; Surinamese: 81%; Dutch
Caribbean: 85% vs. Dutch: 95%). Higher educational level, better mastery of the
Dutch language, having a paid job and home delivery were all independently
associated with the uptake of MCA, and also partially explained ethnic
differences in the uptake of MCA. Mothers who received MCA more often breastfed,
more often gave vitamin K when not breastfeeding, and more often lived in smoke
free homes. The protective effect of MCA was stronger for non-Western mothers
than for Dutch mothers. CONCLUSION: Mothers of non-Western origin make less use
of professional MCA. Given that the use of MCA is associated with a less risk
behaviour around infants, efforts should be made to improve the accessibility of
professional MCA for mothers of non-Western origin.
PMID- 25139652
TI - [Interaction between NSAIDs and acetylsalicylic acid disregarded].
AB - In 2013 the European Medicines Agency declared that diclofenac is contraindicated
in patients with arterial thrombotic complications, based on a meta-analysis of
randomised controlled trials on the adverse reactions of NSAIDs. The same
decision was taken for coxibs some years earlier. The Dutch authorities (CBG/MEB)
informed physicians and pharmacists about this decision without taking into
account whether these patients were using prophylactic acetylsalicylic acid or
not. It has been shown that NSAIDs with high COX-1 affinity like ibuprofen and
naproxen cause a pharmacodynamic interaction with the inhibition of thromboxane
synthesis by acetylsalicylic acid. This interaction does not occur with
relatively COX-2-selective NSAIDs such as coxibs and diclofenac. Therefore, in
patients who use acetylsalicylic acid for thromboprophylaxis, contraindicating
coxibs or diclofenac is not justified, on the contrary: they are preferable.
PMID- 25139653
TI - [Potential lowering of sepsis-related mortality via screening and implementation
of guidelines].
AB - The incidence of sepsis continues to increase. However, over the past decade
marked reductions in sepsis-related in-hospital mortality have been reported.
Large variations in the presentation and severity of illness may be encountered
in ICU patients with severe sepsis, which might preclude the success of screening
and guideline programmes. However, the authors of this article were able to prove
that a national programme involving screening and a package of interventions did
lower relative in-hospital mortality by 16.7% over 3.5 years in 52 participating
hospitals in the Netherlands. In-hospital mortality did not change in 30 non
participating hospitals. Therefore, the authors recommend implementing updated
guidelines, sepsis quality indicators and programmes with a package of
interventions to further reduce sepsis mortality. Furthermore, additional
research on long term consequences in sepsis survivors is warranted.
PMID- 25139654
TI - Fetal growth restriction as a perinatal and long-term health problem: clinical
challenges and opportunities for future (4P) fetal medicine.
PMID- 25139655
TI - Nanofiber scaffolds for treatment of spinal cord injury.
AB - Spinal cord injury (SCI) is a common neurologic disorder that results in loss of
sensory function and mobility. It is well documented that tissue engineering is a
potential therapeutic strategy for treatment of SCI. In this connection, various
biomaterials have been explored to meet the needs of SCI tissue engineering and
these include natural materials, synthetic biodegradable polymers and synthetic
non- degradable polymers. Nanofiber scaffolds are newly emerging biomaterials
that have been widely utilized in tissue engineering recently. In comparison to
the traditional biomaterials, nanofibers have advantages in topography and
porosity, thus mimicking the naturally occurring extracellular matrix. Besides,
they exhibit excellent biocompatibility with low immunogenicity, and furthermore
they are endowed with properties that help to bridge the lesion cavity or gap,
and serve as an effective delivery system for graft cells or therapeutic drugs.
This review summarizes some of the unique properties of nanofiber scaffolds which
are critical to their potential application in treatment of injured spinal cord.
PMID- 25139656
TI - Hereditary cancer syndromes with high risk of endometrial and ovarian cancer:
surgical options for personalized care.
AB - Cancer genomics has increased our recognition of specific hereditary cancer
mutations. Hereditary breast and ovarian cancer (HBOC) syndrome and Lynch
syndrome are two such entities in which women carrying specific mutations may be
at high risk for developing breast, ovarian, and/or endometrial cancers. Risk
reducing surgery such as prophylactic mastectomy, oophorectomy, and/or
hysterectomy may allow women to decrease these risks after completing
childbearing. Background, indications, and consequences of these procedures are
reviewed.
PMID- 25139657
TI - Characterization of a mutant glucose isomerase from Thermoanaerobacterium
saccharolyticum.
AB - A series of site-directed mutant glucose isomerase at tryptophan 139 from
Thermoanaerobacterium saccharolyticum strain B6A were purified to gel
electrophoretic homogeneity, and the biochemical properties were determined.
W139F mutation is the most efficient mutant derivative with a tenfold increase in
its catalytic efficiency toward glucose compared with the native GI. With a
maximal activity at 80 degrees C of 59.58 U/mg on glucose, this mutant
derivative is the most active type ever reported. The enzyme activity was maximal
at 90 degrees C and like other glucose isomerase, this mutant enzyme required
Co(2+) or Mg(2+) for enzyme activity and thermal stability (stable for 20 h at 80
degrees C in the absence of substrate). Its optimum pH was around 7.0, and it
had 86 % of its maximum activity at pH 6.0 incubated for 12 h at 60 degrees C.
This enzyme was determined as thermostable and weak-acid stable. These findings
indicated that the mutant GI W139F from T. saccharolyticum strain B6A is
appropriate for use as a potential candidate for high-fructose corn syrup
producing enzyme.
PMID- 25139658
TI - Inactivation of Aleutian mink disease virus through high temperature exposure in
vitro and under field-based composting conditions.
AB - Disposal of manure contaminated with Aleutian mink disease virus (AMDV) is a
significant concern to the mink industry. Inactivation of AMDV under field
conditions has received limited attention in the scientific literature. We
evaluated the thermal inactivation of AMDV in vitro and during composting of mink
manure. Spleen homogenate containing AMDV was heated under controlled conditions
at 45 degrees C, 55 degrees C, and 65 degrees C for 3 days. Results of the in
vitro study identified complete absence of viral replication in mink at 65
degrees C only. Next, manure-mixed AMDV packed in polyester pouches was inserted
in different layers of three replicate mink manure compost piles. The virus was
retrieved after the compost piles had undergone a heating period and subsequently
returned to ambient temperatures. Temperature regimes in the compost piles were
categorized as >=65 degrees C, >=60-64 degrees C, and >=55-59 degrees C.
Initially, layer-wise composite virus samples were assayed for virus replication
in mink. Twenty-one-day post-inoculation (p.i.) plasma tested for AMDV and
antibodies indicated infection in 40%, 80%, and 100% of mink inoculated from
samples originating from the top, center and bottom layers of the piles,
respectively. Subsequently, the virus was extracted from individual pouches in
compost layers achieving thermal activity >=65 degrees C and was tested in mink.
No antibodies or virus was detected in plasma taken weekly up to day 21 p.i. PCR
data of bone marrow and lymph nodes collected on day 21 p.i. also showed no AMDV.
However, mink that received virus from positive control manure indicated
infection in their plasma as early as 1 week p.i.
PMID- 25139659
TI - Evaluating the potential of marine Bacteriovorax sp. DA5 as a biocontrol agent
against vibriosis in Litopenaeus vannamei larvae.
AB - The potential application of Bdellovibrio-and-like organisms (BALOs) for the
biocontrol of bacterial diseases has been widely recognized. However, no marine
BALOs have been reported for Vibrio-related infections in penaeid shrimp. In the
present study, the bacteriolytic ability of the marine Bacteriovorax strain DA5
against Vibrio alginolyticus zouA was examined by cocultivation and electron
microscopy, and optimal lysis was observed at 30-35 degrees C and 20-300/00
salinity along with a high multiplicity of infection. Then, we showed that
experimentally infected Litopenaeus vannamei larvae exhibited significantly
higher survival with incremental DA5 levels. Finally, variation in the bacterial
counts and the bacterial community in larval rearing water was investigated after
prophylactic application of DA5. The elimination effect of DA5 on vibrios was
visible at early time points, whereas only a few non-dominant bacteria, rather
than the predominant populations, were affected through analysis of denaturing
gradient gel electrophoresis of the 16S rDNA V3 region. Accordingly, the
prophylactic and therapeutic efficacies of DA5 on vibriosis associated with L.
vannamei could markedly enhance larval survivability, and these results will
facilitate the application of marine Bacteriovorax to control vibriosis in shrimp
larviculture.
PMID- 25139660
TI - Recent developments in the effects of nitric oxide-donating statins on
cardiovascular disease through regulation of tetrahydrobiopterin and nitric
oxide.
AB - Since the discovery of the importance of nitric oxide (NO) to the human body
three decades ago, numerous laboratory and clinical studies have been done to
explore its potential therapeutic actions on many organs. In the cardiovascular
system, NO works as a volatile signaling molecule regulating the vascular
permeability and vascular tone, preventing thrombosis and inflammation, as well
as inhibiting the smooth muscle hyperplasia. Thus, NO is important in the
prevention and treatment of cardiovascular disease. NO is synthesized by NO
synthase (NOS) with tetrahydrobiopterin (BH4) as the crucial cofactor. Many
studies have been done to form nitric oxide donors so as to deliver NO directly
to the vessel walls. In addition, NO moieties have been incorporated into
existing therapeutic agents to enhance the NO bioavailability, including statins.
Statins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA), the rate
limiting enzyme of the mevalonate pathway. By inhibiting this pathway, statins
lower blood cholesterol and exert their pleiotropic effects through activity in
reaction cascades, such as Rho/ROCK and Rac 1/NADPH oxidase pathways. Statins
have also been observed to implement their non-lipid effects by promoting BH4
synthesis with increase of NO bioavailability. Furthermore, NO-donating statins
in laboratory studies have demonstrated to produce better therapeutic effects
than their parent's drugs. They offer better anti-inflammatory, anti
proliferative and antithrombotic actions on cardiovascular system. They also
cause better revascularization in peripheral ischemia and produce greater
enhancement in limb reperfusion and salvage. In addition, it has been shown that
NO-donating statin caused less myotoxicity, the most common side effect related
to treatment with statins. The initial studies have demonstrated the superior
therapeutic effects of NO-donating statins while producing fewer side effects.
PMID- 25139661
TI - Laparoscopic sleeve gastrectomy as a weight reduction strategy in obese patients
after kidney transplantation.
AB - Morbid obesity is associated with increased graft loss and shortened graft
survival in kidney transplant patients. Treating obesity in transplant patients
may improve graft outcomes. Laparoscopic sleeve gastrectomy (LSG), an effective
bariatric operation, is relatively unlikely to interfere with absorption of anti
rejection medications. Data on relevant renal function parameters were collected
from all LSGs performed on renal transplant patients at our center (n = 10). The
procedure was successful in eight patients, with no mortality, graft rejection or
dysfunction. The median age and follow-up were 57 years and 14 months,
respectively. Seven patients had over 1 year of follow-up. The median
preoperative weight and BMI were 119 kg (96-152) and 42 kg/m(2) (37-49),
respectively. The median hospital stay was 4 days. The median postoperative
weight and BMI at 6 months and 1 year were 86 kg and 31 kg/m(2) and 83 kg and 29
kg/m(2) , respectively. Urinary protein excretion and serum creatinine decreased
significantly in all patients (p < 0.05). One patient developed two
complications, acute renal failure and sleeve stricture, both of which resolved
with treatment. LSG provided effective weight loss in renal transplant patients
without adverse effects on graft function and immunosuppression.
PMID- 25139662
TI - Progressive rash and fever in an infant.
PMID- 25139663
TI - Would the Use of Bedside Bladder Ultrasound Decrease the Necessity of Invasive
Bladder Catheterization in the Pediatric Intensive Care Unit?
PMID- 25139664
TI - Breastfeeding in African Americans may not depend on sleep arrangement: a mixed
methods study.
AB - BACKGROUND: Despite high bedsharing rates, breastfeeding rates are low among
African Americans. OBJECTIVE: Describe the association between breastfeeding and
bedsharing; elucidate barriers to breastfeeding in African Americans. METHODS:
African American mothers with infants <6 months were recruited for this cross
sectional, mixed-methods study and completed an infant care practices survey. A
subgroup participated in focus groups or individual interviews. RESULTS: A total
of 412 completed the survey; 83 participated in a focus group or interview. Lower
socioeconomic status mothers were more likely to breastfeed exclusively or at all
if they bedshared (P = .02 and P = .01, respectively). Bedsharing was not
associated with breastfeeding among higher socioeconomic status mothers. Breast
pain, lack of support, and maternal skepticism about breastfeeding benefits were
barriers; the latter was a recurrent theme among nonbreastfeeding mothers.
CONCLUSIONS: While bedsharing is associated with breastfeeding in lower
socioeconomic groups, it is not in higher socioeconomic African American groups.
Skepticism about breastfeeding benefits may contribute to low breastfeeding rates
in African Americans.
PMID- 25139665
TI - Copper-mediated C6-selective dehydrogenative heteroarylation of 2-pyridones with
1,3-azoles.
AB - A copper-mediated C6-selective dehydrogenative heteroarylation of 2-pyridones
with 1,3-azoles has been developed. The reaction proceeded smoothly by twofold C
H cleavage even in the absence of noble-metal catalysts. The observed site
selectivity was directed by a pyridyl substituent on the nitrogen atom of the
pyridone ring. This directing group was readily removed after the coupling event,
thus leading to 2-pyridone derivatives with a free N-H group. Moreover, in some
cases, catalytic turnover of the Cu salt was also possible with the ideal
terminal oxidant: molecular oxygen in air.
PMID- 25139666
TI - Family based genome-wide copy number scan identifies complex rearrangements at
17q21.31 in dyslexics.
AB - Developmental dyslexia (DD) is a complex heritable disorder with unexpected
difficulty in learning to read and spell despite adequate intelligence,
education, environment, and normal senses. We performed genome-wide screening for
copy number variations (CNVs) in 10 large Indian dyslexic families using
Affymetrix Genome-Wide Human SNP Array 6.0. Results revealed the complex genomic
rearrangements due to one non-contiguous deletion and five contiguous micro
duplications and micro deletions at 17q21.31 region in three dyslexic families.
CNVs in this region harbor the genes KIAA1267, LRRC37A, ARL17A/B, NSFP1, and NSF.
The CNVs in case 1 and case 2 at this locus were found to be in homozygous state
and case 3 was a de novo CNV. These CNVs were found with at least one CNV having
a common break and end points in the parents. This cluster of genes containing
NSF is implicated in learning, cognition, and memory, though not formally
associated with dyslexia. Molecular network analysis of these and other dyslexia
related module genes suggests NSF and other genes to be associated with
cellular/vesicular membrane fusion and synaptic transmission. Thus, we suggest
that NSF in this cluster would be the nearest gene responsible for the learning
disability phenotype.
PMID- 25139668
TI - The role of parents in children's school life: student motivation and socio
emotional functioning.
PMID- 25139667
TI - Comprehensive disease control (CDC): what does achieving CDC mean for patients
with rheumatoid arthritis?
AB - BACKGROUND: This study assessed the impact of simultaneous achievement of
clinical, functional and structural efficacy, herein referred to as comprehensive
disease control (CDC), on short-term and long-term work-related outcomes, health
related quality of life (HRQoL), pain and fatigue. METHODS: Data were pooled from
three randomised trials of adalimumab plus methotrexate for treatment of early
stage or late-stage rheumatoid arthritis (RA). CDC was defined as 28-joint
Disease Activity Score using C reactive protein <2.6, Health Assessment
Questionnaire <0.5 and change from baseline in modified Total Sharp Score <=0.5.
Changes in scores at weeks 26 and 52 for work-related outcomes, Short Form 36 (SF
36) physical (PCS) and mental component scores (MCS), a Visual Analogue Scale
measuring pain (VAS-Pain) and Functional Assessment of Chronic Illness Therapy
Fatigue (FACIT-F) were compared between patient groups defined by achievement of
CDC at week 26 using linear regression with adjustment for baseline scores.
RESULTS: Patients with RA who achieved CDC at week 26 (n=200) had significantly
greater improvements in VAS-Pain (46.9 vs 26.9; p<0.0001), FACIT-F (13.3 vs 7.5;
p<0.0001), SF-36 PCS (19.7 vs 8.9; p<0.0001) and SF-36 MCS (8.1 vs 5.0; p=0.0004)
than those who did not (n=1267). Results were consistent at week 52 and among
methotrexate-naive patients with early RA, methotrexate-experienced patients with
late-stage RA and patients with inadequate response to methotrexate. CONCLUSIONS:
Patients with RA who achieved CDC at week 26 had improved short-term and long
term HRQoL, pain, fatigue and work-related outcomes compared with patients who do
not. These results demonstrate that the joint achievement of all CDC components
provides meaningful benefits to patients. TRIAL REGISTRATION NUMBERS: DE019:
NCT00195702, PREMIER: NCT00195702, OPTIMA: NCT00195702.
PMID- 25139669
TI - Production of transgenic dairy goat expressing human alpha-lactalbumin by somatic
cell nuclear transfer.
AB - Production of human alpha-lactalbumin (halpha-LA) transgenic cloned dairy goats
has great potential in improving the nutritional value and perhaps increasing the
yield of dairy goat milk. Here, a mammary-specific expression vector 5A,
harboring goat beta-lactoglobulin (betaLG) promoter, the halpha-LA gene, neo(r)
and EGFP dual markers, was constructed. Then, it was effectively transfected into
goat mammary epithelial cells (GMECs) and the expression of halpha-LA was
investigated. Both the halpha-LA transcript and protein were detected in the
transfected GMECs after the induction of hormonal signals. In addition, the 5A
vector was introduced into dairy goat fetal fibroblasts (transfection efficiency
~60-70%) to prepare competent transgenic donor cells. A total of 121 transgenic
fibroblast clones were isolated by 96-well cell culture plates and screened with
nested-PCR amplification and EGFP fluorescence. After being frozen for 8 months,
the transgenic cells still showed high viabilities, verifying their ability as
donor cells. Dairy goat cloned embryos were produced from these halpha-LA
transgenic donor cells by somatic cell nuclear transfer (SCNT), and the rates of
fusion, cleavage, and the development to blastocyst stages were 81.8, 84.4, and
20.0%, respectively. A total of 726 reconstructed embryos derived from the
transgenic cells were transferred to 74 recipients and pregnancy was confirmed at
90 days in 12 goats. Of six female kids born, two carried halpha-LA and the
halpha-LA protein was detected in their milk. This study provides an effective
system to prepare SCNT donor cells and transgenic animals for human recombinant
proteins.
PMID- 25139670
TI - Skeletal defects in Osterix-Cre transgenic mice.
AB - Cre/loxP recombination is a powerful strategy widely used for in vivo conditional
gene targeting. This technique has made possible many important discoveries of
gene function in normal and disease biology. However, due to the transgenic
nature of most Cre mouse strains undesired phenotypes occasionally occur in Cre
mice. Here we report skeletal defects in Osterix-Cre (Osx-Cre) transgenic mice
including delayed calvarial ossification and fracture calluses at multiple
skeletal sites. These data suggest that Osx-Cre containing controls should be
used for both in vivo and in vitro skeletal analyses of conditional knockout mice
generated with this Osx-Cre mouse strain.
PMID- 25139671
TI - Cytological Features of Carcinosarcoma ex Pleomorphic Adenoma of the Parotid
Gland: A Case Report.
AB - BACKGROUND: Carcinosarcoma of the salivary gland is an extremely rare tumor
composed of carcinomatous and sarcomatoid components. This report describes the
cytological and pathological findings of a case of carcinosarcoma ex pleomorphic
adenoma arising in the right parotid gland. CASE: A 47-year-old female visited a
hospital with swelling of the right parotid region, slight pain and facial palsy.
Fine-needle aspiration smears showed both clustered epithelium-like cells and
singly scattered cells in a necrotic background. The cells, especially the
latter, exhibited significant cellular pleomorphism and had irregularly shaped
nuclei. Myxoid stroma-like cell clusters without cellular atypism were also seen.
The right parotid gland was resected, and the tumor tissue was histologically
diagnosed as carcinosarcoma ex pleomorphic adenoma. CONCLUSION: The cytological
findings of carcinosarcoma ex pleomorphic adenoma have been reported in very few
cases. In the present case, various components, including the presence of
atypical epithelium-like cell clusters and singly scattered atypical cells with
stromal components on cytological specimens, led to consideration of the
diagnosis of carcinosarcoma ex pleomorphic adenoma.
PMID- 25139672
TI - CSF levels of Abeta1-38/Abeta1-40/Abeta1-42 and (11)C PiB-PET studies in three
clinical variants of primary progressive aphasia and Alzheimer's disease.
AB - Primary progressive aphasia (PPA) is a cognitive syndrome characterized by
progressive and isolated language impairments due to neurodegenerative diseases.
Recently, an international group of experts published a Consensus Classification
of the three PPA clinical variants (naPPA, svPPA and lvPPA). We analyzed 24
patients with PPA by cognitive functions, neuroimaging (MRI, (99 m)Tc ECD-SPECT,
(11)C PiB-PET and FDG-PET) and cerebrospinal fluid (CSF) analysis (ptau-181,
Abeta1-42, Abeta1-40 and Abeta1-38), to elucidate relationships between
neuroimaging studies and biochemical findings in the three PPA clinical variants.
Cognitive and speech functions were measured by mini-mental state examination and
standard language test of aphasia. The patients with lvPPA showed significant
decreases in CSF Abeta1-42 and ratios of Abeta1-42/Abeta1-40 and Abeta1-42/Abeta1
38, and significant increases in CSF ptau-181 and ratios of ptau-181/Abeta1-42
and ptau-181/Abeta1-38; these findings were similar to those of patients with
Alzheimer's disease (AD). We observed a higher frequency of the ApoE epsilon4
allele in the lvPPA patients relative to the two other PPA variants. In (11)C PiB
PET of lvPPA patients, PiB positive findings were detected in cortices of
frontal, temporal and parietal lobes and the posterior cingulate, where massive
Abeta may accumulate due to AD. Our results of AD-CSF markers including Abeta1-38
and (11)C PiB-PET in the lvPPA patients demonstrate a common pathological
mechanism with the occurrence of AD.
PMID- 25139673
TI - Homology modeling, molecular dynamics, and docking studies of pattern-recognition
transmembrane protein-lipopolysaccharide and beta-1,3 glucan-binding protein from
Fenneropenaeus indicus.
AB - Lipopolysaccharide and beta-1,3 glucan-binding protein (LGBP) is a family of
pattern-recognition transmembrane proteins (PRPs) which plays a vital role in the
immune mechanism of crustaceans in adverse conditions. Fenneropenaeus indicus
LGBP-deduced amino acid has conserved potential recognition motif for beta-1,3
linkages of polysaccharides and putative RGD (Arg-Gly-Asp) cell adhesion sites
for the activation of innate defense mechanism. In order to understand the
stimulating activity of beta-1,3 glucan (beta-glucan) and its interaction with
LGBP, a 3D model of LGBP is generated. Molecular docking is performed with this
model, and the results indicate Arg71 with strong hydrogen bond from RGD domain
of LGBP. Moreover, from the docking studies, we also suggest that Arg34, Lys68,
Val135, and Ala146 in LGBP are important amino acid residues in binding as they
have strong bonding interaction in the active site of LGBP. In our in vitro
studies, yeast agglutination results suggest that shrimp F. indicus LGBP
possesses sugar binding and recognition sites in its structure, which is
responsible for agglutination reaction. Our results were synchronized with the
already reported evidence both in vivo and in vitro experiments. This
investigation may be valuable for further experimental investigation in the
synthesis of novel immunomodulator.
PMID- 25139674
TI - Progression of muscle histopathology but not of spliceopathy in myotonic
dystrophy type 2.
AB - Myotonic dystrophy type 2 (DM2) is an autosomal dominant progressive disease
involving skeletal and cardiac muscle and brain. It is caused by a
tetranucleotide repeat within the first intron of the CNBP gene that leads to an
alteration of the alternative splicing of several genes. To understand the
molecular mechanisms that play a role in DM2 progression, the evolution of
skeletal muscle histopathology and biomolecular findings in successive biopsies
have been studied. Biceps brachii biopsies from 5 DM2 patients who underwent two
successive biopsies at different years of age have been used. Muscle
histopathology has been assessed on sections immunostained with fast or slow
myosin. FISH in combination with MBNL1-immunofluorescence has been performed to
evaluate ribonuclear inclusion and MBNL1 foci dimensions in myonuclei. Gene and
protein expression and alteration of alternative splicing of several genes have
been evaluated over time. All DM2 patients examined show a worsening of muscle
histopathology and an increase of foci dimensions over time. The progressive
worsening of myotonia in DM2 patients may be due to the decrease of CLCN1 mRNA
observed in all patients examined. However, a worsening of alternative splicing
alterations has not been evidenced over time. The data obtained in this study
confirm that DM2 is a slow progression disease since histological and
biomolecular alterations observed in skeletal muscle are minimal even after 10
year interval. The data indicate that muscle morphological alterations evolve
more rapidly over time than the molecular changes thus indicating that muscle
biopsy is a more sensitive tool than biomolecular markers to assess disease
progression at muscle level.
PMID- 25139675
TI - Beneficial effect of cilostazol-mediated neuronal repair following trimethyltin
induced neuronal loss in the dentate gyrus.
AB - Cilostazol acts as an antiplatelet agent and has other pleiotropic effects based
on phosphodiesterase-3-dependent mechanisms. We evaluated whether cilostazol
would have a beneficial effect on neuronal repair following hippocampal neuronal
damage by using a mouse model of trimethyltin (TMT)-induced neuronal loss/self
repair in the hippocampal dentate gyrus [Ogita et al. (2005) J Neurosci Res
82:609-621]; these mice will hereafter be referred to as impaired animals. A
single treatment with cilostazol (10 mg/kg, i.p.) produced no significant change
in the number of 5-bromo-2'-deoxyuridine (BrdU)-incorporating cells in the
dentate granule cell layer (GCL) or subgranular zone on day 3 after TMT
treatment. However, chronic treatment with cilostazol on days 3-15 posttreatment
resulted in an increase in the number of BrdU-incorporating cells in the dentate
GCL of the impaired animals, and these cells were positive for neuronal nuclear
antigen or doublecortin. Cilostazol was effective in elevating the level of
phosphorylated cyclic adrenosine monophosphate response element-binding protein
(pCREB) in the dentate gyrus of impaired animals. The results of a forced
swimming test revealed that the chronic treatment with cilostazol improved the
depression-like behavior seen in the impaired animals. In the cultures of
hippocampal neural stem/progenitor cells, exposure to cilostazol produced not
only enhancement of proliferation activity but also elevation of pCREB levels.
Taken together, our data suggest that cilostazol has a beneficial effect on
neuronal repair following neuronal loss in the dentate gyrus through promotion of
proliferation and/or neuronal differentiation of neural progenitor cells in the
subgranular zone.
PMID- 25139676
TI - Robotic-assisted fluorescence sentinel lymph node mapping using multimodal image
guidance in an animal model.
AB - OBJECTIVE: To investigate positron emission tomography/computed tomography
(PET/CT) preoperative imaging and intraoperative detection of a fluorescent
labeled receptor-targeted radiopharmaceutical in a prostate cancer animal model.
MATERIALS AND METHODS: Three male beagle dogs underwent an intraprostatic
injection of fluorescent-tagged tilmanocept, radiolabeled with both gallium Ga-68
and technetium Tc-99m. One hour after injection, a pelvic PET/CT scan was
performed for preoperative sentinel lymph node (SLN) mapping. The definition of
SLN was a standardized uptake value that exceeded 5% of the lymph node with the
highest standardized uptake value. Thirty-six hours later, we performed robotic
assisted SLN dissection using a fluorescence-capable camera system. Fluorescent
lymph nodes were clipped, the abdomen was opened, and the pelvic and
retroperitoneal nodes were excised. All excised nodal packets were assayed by in
vitro nuclear counting and reported as the percentage of injected dose. RESULTS:
Preoperative PET/CT imaging identified a median of 3 SLNs per animal. All SLNs
(100%) identified by the PET/CT were fluorescent during robotic-assisted lymph
node dissection. Of all fluorescent nodes visualized by the camera system, 9 of
12 nodes (75%) satisfied the 5% rule defined by the PET/CT scan. The 2 lymph
nodes that did not qualify accumulated <0.002% of the injected dose. CONCLUSION:
Fluorescent-labeled tilmanocept has optimal logistic properties to obtain
preoperative PET/CT and subsequent real-time intraoperative confirmation during
robotic-assisted SLN dissection.
PMID- 25139677
TI - High-throughput nucleoside phosphate monitoring in mammalian cell fed-batch
cultivation using quantitative matrix-assisted laser desorption/ionization time
of-flight mass spectrometry.
AB - Current methods for monitoring multiple intracellular metabolite levels in
parallel are limited in sample throughput capabilities and analyte selectivity.
This article presents a novel high-throughput method based on matrix-assisted
laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) for
monitoring intracellular metabolite levels in fed-batch processes. The MALDI-TOF
MS method presented here is based on a new microarray sample target and allows
the detection of nucleoside phosphates and various other metabolites using stable
isotope labeled internal standards. With short sample preparation steps and thus
high sample throughput capabilities, the method is suitable for monitoring
mammalian cell cultures, such as antibody producing hybridoma cell lines in
industrial environments. The method is capable of reducing the runtime of
standard LC-UV methods to approximately 1 min per sample (including 10 technical
replicates). Its performance is exemplarily demonstrated in an 8-day monitoring
experiment of independently controlled fed-batches, containing an antibody
producing mouse hybridoma cell culture. The monitoring profiles clearly confirmed
differences between cultivation conditions. Hypothermia and hyperosmolarity were
studied in four bioreactors, where hypothermia was found to have a positive
effect on the longevity of the cell culture, whereas hyperosmolarity lead to an
arrest of cell proliferation. The results are in good agreement with HPLC-UV
cross validation experiments. Subsequent principal component analysis (PCA)
clearly separates the different bioreactor conditions based on the measured mass
spectral profiles. This method is not limited to any cell line and can be applied
as a process analytical tool in biotechnological processes.
PMID- 25139678
TI - Structural insights into binding of small molecule inhibitors to Enhancer of
Zeste Homolog 2.
AB - Enhancer of Zeste Homolog 2 (EZH2) is a SET domain protein lysine
methyltransferase (PKMT) which has recently emerged as a chemically tractable and
therapeutically promising epigenetic target, evidenced by the discovery and
characterization of potent and highly selective EZH2 inhibitors. However, no
experimental structures of the inhibitors co-crystallized to EZH2 have been
resolved, and the structural basis for their activity and selectivity remains
unknown. Considering the need to minimize cross-reactivity between prospective
PKMT inhibitors, much can be learned from understanding the molecular basis for
selective inhibition of EZH2. Thus, to elucidate the binding of small-molecule
inhibitors to EZH2, we have developed a model of its fully-formed cofactor
binding site and used it to carry out molecular dynamics simulations of protein
ligand complexes, followed by molecular mechanics/generalized born surface area
calculations. The obtained results are in good agreement with biochemical
inhibition data and reflect the structure-activity relationships of known
ligands. Our findings suggest that the variable and flexible post-SET domain
plays an important role in inhibitor binding, allowing possibly distinct binding
modes of inhibitors with only small variations in their structure. Insights from
this study present a good basis for design of novel and optimization of existing
compounds targeting the cofactor binding site of EZH2.
PMID- 25139679
TI - Antimicrobial activity of alexidine, chlorhexidine and cetrimide against
Streptococcus mutans biofilm.
AB - BACKGROUND: The use of antimicrobial solutions has been recommended to disinfect
demineralized dentin prior to placing the filling material. The aim of this study
was to evaluate the ability of several antimicrobials in controlling
Streptococcus mutans (SM) biofilm formed in dentin. METHODS: Antimicrobial
activity of 0.2% and 2% chlorhexidine (CHX), 0.2% cetrimide (CTR) and 0.2%, 0.5%,
1% and 2% alexidine (ALX) was assayed on 1-week SM biofilm formed on standardized
coronal dentin blocks. Results of SM biofilm antimicrobial activity by different
protocols were expressed as the kill percentage of biofilm and the term
"eradication" was used to denote the kill of 100% of the bacterial population. To
compare the efficacies of the different protocols the Student t test was used,
previously subjecting data to the Anscombe transformation. RESULTS: All ALX
concentrations tested and 0.2% CTR achieved a kill percentage higher than 99%,
followed by 2% CHX with percentages above 96% (no statistically significant
difference among them). Whereas 2% ALX and 0.2% CTR respectively showed
eradication in 10 and 9 of the twelve specimens, 0.2% CHX did not produce
eradication in any case. CONCLUSIONS: The present study shows that, when used for
one minute, 2% and 1% alexidine, and 0.2% cetrimide, achieve eradication of
Streptococcus mutans biofilm in most specimens when applied to a dentin
volumetric model.
PMID- 25139680
TI - Food addiction in a Spanish sample of eating disorders: DSM-5 diagnostic subtype
differentiation and validation data.
AB - Although the concept of 'food addiction' (FA) has raised growing interest because
of evidence for similarities between substance dependence and excessive food
intake, there is a lack of studies that explore this construct among the wide
spectrum of eating disorders (EDs). Besides providing validation scores of a
Spanish version of the Yale FA Scale (YFAS-S), this study examined the prevalence
of 'FA' among ED subtypes compared with healthy-eating controls (HCs) and the
association between 'FA' scores, eating symptomatology and general
psychopathology. A sample of 125 adult women with ED, diagnosed according to
Diagnostic and Statistical Manual of Mental Disorders 5 criteria, and 82 healthy
eating women participated in the study. All participants were assessed with the
YFAS-S, the ED Inventory-2 and the Symptom Checklist-Revised. Results showed that
the internal structure of the one-dimensional solution for the YFAS-S was very
good (alpha = 0.95). The YFAS-S has a good discriminative capacity to
differentiate between ED and controls (specificity = 97.6% and sensitivity (Se) =
72.8%; area under receiver operating characteristic curve = 0.90) and a good Se
to screen for specific ED subtypes. YFAS-S scores were associated with higher
levels of negative affect and depression, higher general psychopathology, more
severe eating pathology and greater body mass index. When comparing the
prevalence of 'FA' between ED subtypes, the lowest prevalence of 'FA', measured
with the YFAS-S, was for the anorexia nervosa (AN) restrictive subtype with 50%,
and the highest was for the AN binge-purging subtype (85.7%), followed by bulimia
nervosa (81.5%) and binge eating disorder (76.9%). In conclusion, higher YFAS-S
scores are associated with bingeing ED-subtype patients and with more eating
severity and psychopathology. Although the 'FA' construct is able to
differentiate between ED and HC, it needs to be further explored.
PMID- 25139681
TI - Factors associated with exclusive breastfeeding at hospital discharge in rural
Western Australia.
AB - BACKGROUND: Breastfeeding is accepted as the best way of feeding infants, and
health authorities recommend exclusive breastfeeding to around 6 months of age,
but despite the evidence of its benefits, few mothers meet this goal. Infants who
are exclusively breastfed in the early postpartum period are more likely to
continue breastfeeding at 6 and 12 months, reinforcing the role that Baby
Friendly hospital practices play in supporting exclusive breastfeeding.
OBJECTIVES: This study aimed to determine the rate of breastfeeding initiation
and identify the factors associated with exclusive breastfeeding at discharge
from hospital for rural mothers. METHODS: The prospective cohort study recruited
489 women from hospitals in regional Western Australia following the birth of
their infant. Breastfeeding exclusivity at discharge was assessed based on
mothers' self-reported infant feeding behavior during her hospital stay. The self
administered baseline questionnaire was completed by 427 mothers. RESULTS:
Breastfeeding was initiated by 97.7% of the mothers in this cohort, with 82.7%
exclusively breastfeeding at hospital discharge. The odds of exclusive
breastfeeding at discharge were more than 4 times higher for women whose infants
did not require admission to the special care nursery (adjusted odds ratio [aOR]
= 4.43; 95% confidence interval [CI], 1.98-9.99). Demand feeding (aOR = 3.33; 95%
CI, 1.59-6.95) and 24-hour rooming-in (aOR = 2.31; 95% CI, 1.15-4.62) were also
significant positive factors. CONCLUSION: The findings suggest that hospital
practices are strong predictors of exclusive breastfeeding. Greater emphasis on
Baby-Friendly hospital practices in the early postpartum period may help the
establishment of exclusive breastfeeding, assisting rural mothers to reach
established international breastfeeding recommendations.
PMID- 25139682
TI - Temperature-dependent photoluminescence in light-emitting diodes.
AB - Temperature-dependent photoluminescence (TDPL), one of the most effective and
powerful optical characterisation methods, is widely used to investigate carrier
transport and localized states in semiconductor materials. Resonant excitation
and non-resonant excitation are the two primary methods of researching this
issue. In this study, the application ranges of the different excitation modes
are confirmed by analysing the TDPL characteristics of GaN-based light-emitting
diodes. For resonant excitation, the carriers are generated only in the quantum
wells, and the TDPL features effectively reflect the intrinsic photoluminescence
characteristics within the wells and offer certain advantages in characterising
localized states and the quality of the wells. For non-resonant excitation, both
the wells and barriers are excited, and the carriers that drift from the barriers
can contribute to the luminescence under the driving force of the built-in field,
which causes the existing equations to become inapplicable. Thus, non-resonant
excitation is more suitable than resonant excitation for studying carrier
transport dynamics and evaluating the internal quantum efficiency. The
experimental technique described herein provides fundamental new insights into
the selection of the most appropriate excitation mode for the experimental
analysis of carrier transport and localized states in p-n junction devices.
PMID- 25139683
TI - Binding kinetics, potency, and selectivity of the hepatitis C virus NS3 protease
inhibitors GS-9256 and vedroprevir.
AB - BACKGROUND: GS-9256 and vedroprevir are inhibitors of the hepatitis C virus NS3
protease enzyme, an important drug target. The potency, selectivity, and binding
kinetics of the two compounds were determined using in vitro biochemical assays.
METHODS: Potency of the compounds against NS3 protease and selectivity against a
panel of mammalian proteases were determined through steady-state enzyme
kinetics. Binding kinetics were determined using stopped-flow techniques.
Dissociation rates were measured using dilution methods. RESULTS: GS-9256 and
vedroprevir had measured Ki values of 89 pM and 410 pM, respectively, against
genotype 1b NS3 protease; Ki values were higher against genotype 2a (2.8 nM and
39 nM) and genotype 3 proteases (104 nM and 319 nM) for GS-9256 and vedroprevir,
respectively. Selectivity of GS-9256 and vedroprevir was >10,000-fold against all
tested off-target proteases. Association rate constants of 4*10(5)M(-1)s(-1) and
1*10(6)M(-1)s(-1), respectively, were measured, and dissociation rate constants
of 4.8*10(-5)s(-1) and 2.6*10(-4)s(-1) were determined. CONCLUSIONS: GS-9256 and
vedroprevir are potent inhibitors of NS3 protease with high selectivity against
off-target proteases. They have rapid association kinetics and slow dissociation
kinetics. GENERAL SIGNIFICANCE: The NS3 protease is a key drug target for the
treatment of hepatitis C. The potency, selectivity, and binding kinetics of GS
9256 and vedroprevir constitute a biochemical profile that supports the
evaluation of these compounds in combination with other direct-acting antivirals
in clinical trials for hepatitis C.
PMID- 25139684
TI - Clostridium difficile infection: an undeniably common problem among hematopoietic
transplant recipients.
PMID- 25139688
TI - Risk of premature menopause after treatment for Hodgkin's lymphoma.
PMID- 25139687
TI - Risk of premature menopause after treatment for Hodgkin's lymphoma.
AB - BACKGROUND: Modern treatment of Hodgkin's lymphoma (HL) has transformed its
prognosis but causes late effects, including premature menopause. Cohort studies
of premature menopause risks after treatment have been relatively small, and
knowledge about these risks is limited. METHODS: Nonsurgical menopause risk was
analyzed in 2127 women treated for HL in England and Wales at ages younger than
36 years from 1960 through 2004 and followed to 2003 through 2012. Risks were
estimated using Cox regression, modified Poisson regression, and competing risks.
All statistical tests were two-sided. RESULTS: During follow-up, 605 patients
underwent nonsurgical menopause before age 40 years. Risk of premature menopause
increased more than 20-fold after ovarian radiotherapy, alkylating chemotherapy
other than dacarbazine, or BEAM (bis-chloroethylnitrosourea [BCNU], etoposide,
cytarabine, melphalan) chemotherapy for stem cell transplantation, but was not
statistically significantly raised after adriamycin, bleomycin, vinblastine,
dacarbazine (ABVD). Menopause generally occurred sooner after ovarian
radiotherapy (62.5% within five years of >=5 Gy treatment) and BEAM (50.9% within
five years) than after alkylating chemotherapy (24.2% within five years of >=6
cycles), and after treatment at older than at younger ages. Cumulative risk of
menopause by age 40 years was 81.3% after greater than or equal to 5Gy ovarian
radiotherapy, 75.3% after BEAM, 49.1% after greater than or equal to 6 cycles
alkylating chemotherapy, 1.4% after ABVD, and 3.0% after solely
supradiaphragmatic radiotherapy. Tables of individualized risk information for
patients by future period, treatment type, dose and age are provided.
CONCLUSIONS: Patients treated with HL need to plan intended pregnancies using
personalized information on their risk of menopause by different future time
points.
PMID- 25139689
TI - Pre-transplant achievement of negativity in minimal residual disease and French
American-British L1 morphology predict superior outcome after allogeneic
transplant for Philadelphia chromosome positive acute lymphoblastic leukemia: an
analysis of Southeast Asian patients.
AB - To better understand predictive factors and improve the clinical outcome of
allogeneic transplant for patients with Philadelphia positive acute lymphoblastic
leukemia, we analyzed 67 Southeast Asian patients transplanted in our
institutions. Multivariate analysis showed that disease status before transplant,
year of transplant and, interestingly, French-American-British (FAB) subtype had
a significant impact on overall survival (OS) and non-relapse mortality. Patients
who were minimal residual disease (MRD) negative at transplant had a 3-year OS of
73% compared to those who were MRD positive (45%) and refractory (0%). The 3-year
cumulative incidence of relapse was 18% and 36% for the MRD negative and positive
groups, respectively. FAB L1 subtype had a significantly superior 3-year OS of
63% vs. 29% for L2 subtype. Pre-transplant use of a tyrosine kinase inhibitor
significantly improved outcomes in univariate but not multivariate analysis, as
it served to induce more patients into MRD negativity, which was the factor that
directly improved transplant outcome.
PMID- 25139690
TI - Absolute lymphocyte count is unrelated to overall survival in newly diagnosed
elderly patients with multiple myeloma treated with immunomodulatory drugs.
PMID- 25139691
TI - Outcome of pediatric patients with lymphoma following stem cell transplant: a
single institution report.
AB - Hematopoietic stem cell transplant (HSCT) is recommended for pediatric patients
with relapsed/refractory lymphoma even though the evidence for this is limited.
We retrospectively reviewed records of 57 patients (29 Hodgkin lymphoma [HL], 28
non-Hodgkin lymphoma [NHL]) who underwent HSCT between 1995 and 2012. All
demonstrated chemoresponsiveness prior to HSCT and 44 patients had a complete
response. All underwent myeloablative conditioning, 38 chemotherapy-based and 19
total body irradiation-based. Forty-one patients received autologous and 16
allogeneic HSCT. Twelve (21%) died within 100 days post-HSCT, and 25 patients
relapsed at a median of 1.6 months post-HSCT. Three patients developed second
malignant neoplasms. Five-year overall survival (OS) was 50.5% and event-free
survival (EFS) was 43.4%. Outcomes for HL were significantly better than those
for NHL (OS 61.9% vs. 38.7% [p = 0.005] and EFS 60.4% vs. 26% [p = 0.008]). In
summary, approximately half of all pediatric patients with lymphoma who failed
first-line therapy and demonstrated chemosensitivity to second-line therapy can
be salvaged with HSCT.
PMID- 25139692
TI - Methylenetetrahydrofolate reductase 677 C> T polymorphism is associated with
acute myeloid leukemia.
PMID- 25139693
TI - Voriconazole toxicity masquerading as septic shock.
PMID- 25139694
TI - Real-world cost-effectiveness in chronic myeloid leukemia: the price of success
during four decades of development from non-targeted treatment to imatinib.
AB - Imatinib has revolutionized the treatment of chronic myeloid leukemia (CML). We
evaluated clinical outcome and cost-effectiveness, using Swedish registry data
based on patients with CML diagnosed 1973-2008. Outcome from three time periods
(I: 1973-1979; II: 1991-1997; III: 2002-2008) associated with symptomatic
treatment, interferon-alpha/stem cell transplant and implementation of imatinib,
respectively, were compared and a lifetime cost-effectiveness model developed.
Survival data from population registries, estimated resource use from clinical
practice and quality of life estimates were employed. Substantial health gains
were noted over time, paralleled by increased treatment costs. Median survival
was 1.9, 4.0 and 13 years during the respective time periods. The incremental
cost-effectiveness ratio (ICER) between periods III and II was ?52,700 per
quality-adjusted life year (QALY) gained. An estimated 80% price reduction of
imatinib, related to patent expiry, would reduce this ICER to ?22,700. Our data
from four decades reveal dramatically improved survival in CML, paralleled by
ICER levels generally accepted by health authorities.
PMID- 25139695
TI - Understanding the polar mechanism of the ene reaction. A DFT study.
AB - The molecular mechanism of ene reactions has been characterised by DFT methods at
the MPWB1K/6-311G(d,p) level of theory. Most reactions take place along a two
stage one-step mechanism in which the C-C bond formation takes place before the
hydrogen transfer process. A very good correlation between the polar character of
the reaction measured by the global electron density transfer at the transition
state and the activation energy has been found. This behaviour allows
establishing a useful classification of ene reactions in N-ene having a very high
activation energy, P-ene reactions having activation energies between 35 and 20
kcal mol(-1), and H-ene reactions having activation energies below 20 kcal mol(
1). ELF topological analysis allows the characterisation of the two-stage one
step mechanism associated with a two-centre nucleophilic/electrophilic
interaction. Formation of the C-C single bond is achieved by the C-to-C coupling
of two pseudoradical centres formed at the two interacting carbon atoms in the
first stage of the reaction. This topological analysis establishes that bonding
changes are non-concerted. Finally, a DFT reactivity analysis makes it possible
to characterise the electrophilic/nucleophilic behaviour of the reagents involved
in ene reactions, and consequently, to predict the feasibility of ene reactions.
PMID- 25139698
TI - Effect of trunk-to-head bathing on physiological responses in newborns.
AB - OBJECTIVE: To determine the effect of trunk-to-head bathing versus the
traditional head-to-trunk bathing on newborns' body temperature, heart rate, and
oxygen saturation. DESIGN: A prospective, two-group, quasi-experimental repeated
measures design. SETTING: A newborn nursery in an urban university hospital.
PARTICIPANTS: Sixty-two healthy full-term newborns. METHODS: Newborns were
randomly assigned to two groups. The newborns in the experimental group were
bathed from trunk to head; those in the control group were bathed from head to
trunk. Measurements of body temperature, heart rate, and oxygen saturation were
obtained at four time points: before the bath, immediately after the bath, 30
minutes after the bath, and 60 minutes after the bath. RESULTS: No significant
differences in body temperature, heart rate, or oxygen saturation were observed
between groups. However, body temperature was significantly different across
measurement times, and there was a significant interaction between group and
measurement time. The mean body temperature dropped 0.2 degrees C after bathing
in both groups, but the experimental group returned to their initial body
temperature more rapidly than the control group. CONCLUSION: These findings
suggest that newborns who were bathed from trunk to head and whose heads were wet
for shorter periods of time benefited with a more rapid recovery of body
temperature and decreased heat loss due to evaporation.
PMID- 25139696
TI - A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to
reconsider electrolyte monitoring regimens after thiazide initiation?
AB - AIMS: Hyponatraemia is one of the major adverse effects of thiazide and thiazide
like diuretics and the leading cause of drug-induced hyponatraemia requiring
hospital admission. We sought to review and analyze all published cases of this
important condition. METHODS: Ovid Medline, Embase, Web of Science and PubMed
electronic databases were searched to identify all relevant articles published
before October 2013. A proportions meta-analysis was undertaken. RESULTS: One
hundred and two articles were identified of which 49 were single patient case
reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79%
were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m(
2) . Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95%
CI 8, 30) days after starting treatment, with mean trough serum sodium
concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0,
3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most
frequently reported drugs were hydrochlorothiazide, indapamide and
bendroflumethiazide. CONCLUSIONS: Patients with thiazide-induced hyponatraemia
were characterized by advanced age, female gender, inappropriate saliuresis and
mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite
previous suggestions. The time from thiazide initiation to presentation with
hyponatraemia suggests that the recommended practice of performing a single
investigation of serum biochemistry 7-14 days after thiazide initiation may be
insufficient or suboptimal. Further larger and more systematic studies of
thiazide-induced hyponatraemia are required.
PMID- 25139699
TI - Circulating SFRP5 levels are elevated in drug-naive recently diagnosed type 2
diabetic patients as compared with prediabetic subjects and controls.
AB - BACKGROUND: Secreted frizzled-related protein 5 (SFRP5) has been linked to
obesity. Results are conflicting regarding its association with type 2 diabetes
(T2D) in humans. We aimed to investigate circulating SFRP5 in prediabetes and T2D
and its potential association with parameters of insulin resistance and beta-cell
function. METHODS: We studied 70 drug-naive T2D patients, 70 prediabetic subjects
and 70 controls. All subjects were body mass index matched to the T2D patients
and overweight or obese. SFRP5, hormones and cytokines levels were measured by
ELISA. RESULTS: Serum SFRP5 levels were elevated in T2D patients as compared with
prediabetic subjects (median 15.6, interquartile range [9-24.5] ng/mL vs 9.8 [5
14.2] ng/mL, p < 0.001, respectively) and controls (15.6 [9-24.5] ng/mL vs 10.4
[6.7-16.6] ng/mL, P < 0.001, respectively). No differences were found in serum
SFRP5 levels between prediabetic subjects and controls (9.8 [5-14.2] ng/mL vs
10.4 [6.7-16.6] ng/mL, p = 0.472, respectively). After adjusting for potential
confounders (age, gender, body mass index, triglycerides, high-density
lipoprotein cholesterol and blood pressure), T2D was still associated with higher
values of SFRP5 as compared with prediabetes in multinomial logistic regression
analysis (fully adjusted odds ratio 3.50, 95% confidence interval 1.40-8.79, p =
0.008). The association was more subtle when comparing T2D with normal glucose
tolerance state (fully adjusted odds ratio 2.18, 95% confidence interval 0.91
5.21, p = 0.078). CONCLUSIONS: Circulating SFRP5 levels were independently
associated with T2D as compared with prediabetes and normal glucose tolerance
state.
PMID- 25139700
TI - "You're in that realm of unpredictability": mateship, loyalty, and men
challenging men who use domestic violence against women.
AB - This study reports on discourse analysis of transcripts from focus group
discussions held with 28 "ordinary" men about domestic violence. Two broad
"mateship" themes emerged: (a) a strong "mateship" discourse that produced
public/private boundaries around discussions about intimate heterosexual
relationships. Policed by the threat of violence, these boundaries prevented some
men from challenging men about their violence. (b) "Loyalty to mates" discourses
constituted attention to men's violence against women as threatening the moral
integrity of all men. Finally, some men positioned themselves against men's
domestic violence, distinguishing their masculinity from men who abuse women.
Implications for prevention campaigns are discussed.
PMID- 25139701
TI - Preparedness of final-year Turkish nursing students for work as a professional
nurse.
AB - AIMS AND OBJECTIVES: To determine the preparedness levels of final-year Turkish
nursing students starting their careers as professional nurses. BACKGROUND: The
transition from nursing student to professional nurse is challenging. One of the
ways to help facilitate this transition is to determine how well students are
prepared to start work. There are limited, but conflicting, results on this
topic. DESIGN: Mixed-methods study. METHODS: Undergraduate nursing students (n =
4490) in their final year of study from 74 Turkish universities were eligible to
participate in this study. Of these, 1804 total students participated from 38
randomly selected universities. Data were collected through an investigator
developed questionnaire (n = 1804) and focus group interviews (n = 57). RESULTS:
Students felt highly prepared to start work (57.6%). Those who were older, male,
graduates of a vocational high school or already working as a nurse felt most
prepared. Students who felt that their education preparation and resources were
adequate felt more prepared. Focus group interviews revealed that students felt
confident in their knowledge of educational theory, but not in clinical skills.
CONCLUSIONS: Students may have felt prepared to start work, but insufficient
clinical experience probably contributed to a lack of confidence in their skills.
The resources of the school, the quality of the education, and the clinical
practice environments were considered most important for the students' perceived
preparedness levels. RELEVANCE TO CLINICAL PRACTICE: An undergraduate education
provides the foundation for successful nurse preparation. A good clinical
environment along with a high-quality education programme can help give students
more confidence in their skills when they join the nursing workforce. Internship
or residency programmes may also facilitate this learning. This is extremely
important for safe, high-quality patient care.
PMID- 25139702
TI - Deviation of sonographic estimated fetal weight from actual birth weight in two
consecutive pregnancies of the same parturients.
AB - OBJECTIVE: To determine whether maternal features affect the accuracy of
sonographic estimated fetal weight (SEFW) by evaluating the consistency of the
systematic error of SEFW with regards to the birth weight (BW) in two consecutive
pregnancies of the same gravida. METHODS: The cohort included women with SEFW
within 1 week of delivery (32-42 weeks' gestation) in two consecutive singleton
pregnancies from 2007 to 2012. The systematic error was calculated as (SEFW -
BW)/BW * 100 and expressed as a percentage of the BW. RESULTS: A total of 636
pregnancies (318 gravidas) were eligible for analysis. The BW and SEFW were
correlated in both first examined (r = 0.873, p < 0.001) and consecutive (r =
0.843, p < 0.001) pregnancies. There was a significant difference in mean
systematic error between first examined and consecutive pregnancies (3.13 +/-
8.95 vs. 0.34 +/- 8.75%, p < 0.001), with a very weak correlation between the two
(r = 0.135, p = 0.16). Nulliparity or multiparity at the first examined pregnancy
was not found to be a significant factor, and in both groups the error was higher
in the first examined pregnancy. There were no significant differences between
parturients with a minor (10% and below) or major (>10%) difference in the
systematic error between the two pregnancies. CONCLUSION: The systematic error
between the SEFW and BW in two consecutive pregnancies is inconsistent,
suggesting that it is unaffected by maternal biometric features.
PMID- 25139703
TI - Staphylococcus aureus bio-products: new biological roles for a pleurodesis agent.
PMID- 25139704
TI - [Acute jaw-thoracic pain and syncope in a 41-year-old man].
AB - A 41-year-old physically active man with no significant past medical history
presented with sudden thoracic pain. The patient was referred to the next
tertiary care hospital. A CT scan showed an ectasia of the ascending aorta with
irregularities of the aortic wall without dissection. Despite initial refusal,
the patient was referred to a university hospital with experience in aortic
surgery. A triphase ECG-synchronized cardiothoracic flash protocol performed on a
256 line CT scanner confirmed an aortic intramural hematoma and a covered aortic
perforation. Shortly afterwards the patient collapsed and had to be resuscitated.
PMID- 25139705
TI - [Pharmacotherapy of solid tumors. New hopes and frustrations].
AB - Recent years have seen dramatic changes in the biological understanding and
treatment of solid tumors. Based on the tumor biology, targeting agents have been
developed which directly affect the underlying genetic or immunological changes
found in specific tumor entities. Significant increases in survival have
delivered the functional proof of the concept of targeted and immunological tumor
therapy. The management and adherence of the patient as well as optimized
cooperation with clinicians are decisive for the results of therapy and disease
control.Several solid tumors are currently under investigation in clinical
studies evaluating the (sequential) therapy with targeting and immunologically
active agents, e.g. tyrosine kinase and mTOR inhibitors, targeting antibodies,
such as bevacizumab, specific antagonists, such as enzalutamide and immunological
checkpoint inhibitors via PD(L)1 and/or CTLA 4 antibodies.Currently approved
agents have dramatically changed the landscape of treatment options especially
for prostate cancer. Such agents include hormone therapy with enzalutamide and
abiraterone, radiotherapy with cabazitaxel and xofigo (radium 223), metastatic
breast cancer (eribulin and everolimus), renal cell carcinoma (sunitinib,
sorafenib, axitinib, everolimus and temsirolimus), non-small cell lung cancer
(crizotinib and afatinib), colorectal cancer and gastrointestinal stromal tumor
(regorafenib) and melanoma (ipilimumab and vemurafenib). The treatment of rarer
tumors, such as pancreatic and hepatocellular cancer and soft tissue sarcoma has
entered the stage of targeted therapy with the approval of nanoparticle albumin
bound (nab)-paclitaxel, sorafenib, and eribulin/pazopanib. Current clinical
trials are focusing on the best time point and sequence of therapy and also
improvement in the management of these promising agents.
PMID- 25139706
TI - [Acute pancreatitis: guideline-based diagnosis and treatment].
AB - Acute pancreatitis is most frequently of biliary or alcoholic origin and less
frequently due to iatrogenic (ERCP, medication) or metabolic causes. Diagnosis is
usually based on abdominal pain and elevation of serum lipase to more than three
times the normal limit. Acute pancreatitis can either resolve quickly following
an oedematous swelling or present as a severe necrotizing form. A major risk is
the systemic inflammatory response syndrome (SIRS), which can cause multi-organ
failure. Prediction of disease course is initially difficult, thus necessitating
immediate therapy and regular re-evaluation. In order to prove or exclude biliary
genesis, abdominal ultrasonography should first be performed and endoscopic
ultrasound may also be required. Primary therapy includes rapid and correctly
dosed fluid substitution. Biliary pancreatitis requires causal treatment. In the
case of cholangitis, stone extraction must be performed immediately; in the
absence of cholangitis, it might be advisable to wait for spontaneous stone
clearance. Timely cholecystectomy is necessary in all cases of biliary
pancreatitis.
PMID- 25139707
TI - A review of methotrexate-associated hepatotoxicity.
AB - Methotrexate is effective not only in treating psoriasis and rheumatoid arthritis
but also various other disorders. The use of methotrexate has been somewhat
limited by concerns regarding its adverse effects, including its potential for
hepatotoxicity. The purpose of this article is to provide an overview of
methotrexate-associated hepatotoxicity, including risk factors, pathogenesis and
recommendations for monitoring it by US, UK and European guidelines, as well as
providing a brief overview of its mechanism of action and of high-dose
methotrexate.
PMID- 25139708
TI - Considering economic analyses in the revision of the preventive vaccination law:
a new direction for health policy-making in Japan?
AB - Evidence of a significant vaccine policy shift can be witnessed not only in the
number of new vaccines available in Japan but also in the way that vaccine policy
is being formulated. In 2010, policy makers decided for the first time ever to
commission economic analyses as a reference in their consideration of subsidy
allocation. This research offers a first hand account of the recent changes in
vaccine policies by examining the decision-making process from the perspective of
the researchers commissioned to perform the economic evaluations. In order to
understand the vaccine policy-making process, a review was made of all the
documents that were distributed and discussed during the government committee
meetings from February 2010 when the revision of the Preventive Vaccination Law
was initially proposed to May 2012 when the final recommendations were made.
Economic evaluations were conducted for seven vaccines under consideration in the
routine immunization program (Haemophilus influenzae type b or Hib, pneumococcal
disease for children and adults, human papillomavirus, varicella, mumps, and
hepatitis B). All were cost-effective options, except the Hib and hepatitis B
vaccines. Nonetheless, all the vaccines were recommended equally for inclusion in
the routine immunization program. While it is significant that policy-makers
decided to commission economic assessments at all, various issues remain
regarding the influence of external pressure, the choice of evaluation methods
and the implications of using cost-effectiveness analyses on the future of
Japanese health policy-making.
PMID- 25139709
TI - The 3 A's of the access process to long-term care for elderly: providers
experiences in a multiple case study in the Netherlands.
AB - The access process is an important step in the care provision to independently
living elderly. Still, little attention has been given to the process of access
to long-term care for older clients. Access can be described by three dimensions:
availability, affordability and acceptability (three A's). In this paper we
address the following question: How do care providers take the three dimensions
of access into account for the access process to their care and related service
provision to independently living elderly? To answer this question we performed a
qualitative study. We used data gathered in a multiple case study in the
Netherlands. This study provides insight in the way long-term care organizations
organize their access process. Not all dimensions were equally present or
acknowledged by the case organizations. The dimension acceptability seems an
important dimension in the access process, as shown by the efforts done in
building a relationship with their clients, mainly through a strong personal
relationship between client and care advisor. In that respect it is remarkable
that the case organizations do not structurally evaluate their access process.
Availability is compromised by practical issues and organizational choices.
Affordability hardly seems an issue. Further research can reveal the underlying
factors that influence the three A dimensions.
PMID- 25139710
TI - An immune dysregulation in MPN.
AB - Myeloproliferative neoplasms (MPNs) are stem cell-derived clonal myeloid
malignancies characterized by a unique somatic mutational profile since three
mutually exclusive mutations (JAK2V617F, MPL, and CALR) sustain the great
majority of the cases. However, clinical observation that autoimmune diseases may
predispose to MPNs, autoimmune disorders or autoimmune phenomena may be
associated with MPNs, and genetic constitutional variants that predispose to
autoimmune disorders or inflammatory phenomena also predispose to MPNs raises a
hypothesis that there might be an autoimmune/inflammatory basis underlying the
pathogenesis of MPNs. Recent studies have documented that MPNs are characterized
by an abnormal activity of key cells of the immune system, for example, increase
in monocyte/macrophage compartment, altered regulatory T cell frequency,
expansion of myeloid-derived suppressor cells, and CD4/natural killer cell
dysfunction. This review is focused on summarizing recent advances in our
understanding of immunological defects in MPNs with accompanying translational
implications.
PMID- 25139711
TI - ArsC3 from Desulfovibrio alaskensis G20, a cation and sulfate-independent highly
efficient arsenate reductase.
AB - Desulfovibrio alaskensis G20, a sulfate-reducing bacterium, contains an arsRBC2C3
operon that encodes two putative arsenate reductases, DaG20_ArsC2 and
DaG20_ArsC3. In this study, resistance assays in E. coli transformed with
plasmids containing either of the two recombinant arsenate reductases, showed
that only DaG20_ArsC3 is functional and able to confer arsenate resistance.
Kinetic studies revealed that this enzyme uses thioredoxin as electron donor and
therefore belongs to Staphylococcus aureus plasmid pI258 and Bacillus subtilis
thioredoxin-coupled arsenate reductases family. Both enzymes from this family
contain a potassium-binding site, but only in Sa_ArsC does potassium actually
binds resulting in a lower K m. Important differences between the S. aureus and
B. subtilis enzymes and DaG20_ArsC3 are observed. DaG20_ArsC3 contains only two
(Asn10, Ser33) of the four (Asn10, Ser33, Thr63, Asp65) conserved amino acid
residues that form the potassium-binding site and the kinetics is not
significantly affected by the presence of either potassium or sulfate ions.
Isothermal titration calorimetry measurements confirmed nonspecific binding of
K(+) and Na(+), corroborating the non-relevance of these cations for catalysis.
Furthermore, the low K m and high k cat values determined for DaG20_ArsC3
revealed that this enzyme is the most catalytically efficient potassium
independent arsenate reductase described so far and, for the first time indicates
that potassium binding is not essential to have low K m, for Trx-arsenate
reductases.
PMID- 25139712
TI - Trends in U.S. emergency department visits for opioid overdose, 1993-2010.
AB - OBJECTIVE: Emergency department (ED) visits for opioid overdose provide an
important marker of acute morbidity. We sought to evaluate national trends of ED
visits for opioid overdose. DESIGN, SETTING, AND PARTICIPANTS: The National
Hospital Ambulatory Medical Care Survey, 1993-2010, was used to identify ED
visits for opioid overdose. OUTCOME MEASURES: Outcome measures were national ED
visit rates for opioid overdose per 100,000 U.S. population and per 100,000 ED
visits. RESULTS: From 1993 to 2010, there were approximately 731,000 ED visits
(95% CI, 586,000-877,000 visits) for opioid overdose, representing an overall
rate of 14 ED visits (95% CI, 12-17 visits) per 100,000 population and 37 ED
visits (95% CI, 31-45 visits) per 100,000 ED visits. Of these, 41% (95% CI, 33
50%) were for prescription opioid overdose. Between 1993 and 2010, the national
visit rate increased from 7 to 27 per 100,000 population (+307%; Ptrend = 0.03),
and from 19 to 63 per 100,000 ED visits (+235%; Ptrend < 0.001). Stratified
analyses of the visit rate per population showed upward, but nonsignificant,
trends across multiple demographic groups and U.S. regions. In stratified
analyses of the visit rate per 100,000 ED visits, the rate increased
significantly in several groups: age <20 years (+1188%; Ptrend = 0.002), age 20
29 years (+155%; Ptrend = 0.04), age >=50 years (+231%; Ptrend = 0.04), female
(+234%; Ptrend = 0.001), male (+80%; Ptrend = 0.04), whites (+187%; Ptrend <
0.001), and patients in the South (+371%; Ptrend < 0.001). CONCLUSION: In a
nationally representative database of U.S. ED visits, we found that the ED visit
rate for opioid overdose quadrupled from 1993 to 2010. Our findings suggest that
previous prevention measures may not be adequate.
PMID- 25139714
TI - B7-H3 expression in colorectal cancer: associations with clinicopathological
parameters and patient outcome.
AB - BACKGROUND: We have previously reported overexpression of the immunoregulatory
protein B7-H3 in colorectal cancer and that nuclear expression predicted poor
outcome in colon cancer patients. The present study was performed to examine the
prognostic role of B7-H3 in an independent colorectal cancer cohort. METHODS:
Using tissue microarrays from 731 colorectal cancer patients, tumour B7-H3
expression was assessed by immunohistochemistry. Associations with
clinicopathological parameters and patient outcome were investigated. RESULTS:
Nuclear expression of B7-H3 in cancer cells was present in 27% of the samples in
the total study cohort, while cytoplasmic/membrane and stromal expression was
seen in 86% and 77% of the samples, respectively. Nuclear B7-H3 had no prognostic
relevance in the complete outcome cohort, neither in colon cancer patients.
However, nuclear B7-H3 was significantly associated with reduced recurrence-free
survival in TNM stage I colorectal cancer patients. CONCLUSIONS: Overexpression
of B7-H3 in colorectal cancer was confirmed, but in contrast to previous results,
nuclear B7-H3 was not a strong prognostic biomarker in this cohort. The
discrepancy might be related to the use of single-core tissue microarrays for
detection of the heterogeneously expressed B7-H3, and the role of B7-H3 in
colorectal cancer still needs further examination.
PMID- 25139715
TI - Influence of wound drainage in primary total knee arthroplasty without
tourniquet.
AB - PURPOSE: Although it remains the golden standard, several authors have questioned
the role of pneumatic tourniquets in primary knee arthroplasty in recent studies.
An intra-articular wound drainage is widely used in the field of total knee
arthroplasty although the benefit of postoperative wound drainage is
controversial in the literature. This study questioned whether the use of an
intra-articular drain is an advance over the lack of a drain in total knee
arthroplasty which is performed without a tourniquet. METHODS: We documented the
ROM, the knee circumference at the upper patellar pole pre-operatively and on
days two, four and six postoperatively. The blood volume and loss was calculated.
As surrogate parameter for wound healing we counted the number of days until no
residual secretion was observed via the wound/drainage site. RESULTS: The results
of our investigation showed a significantly better wound healing without the use
of a drain. All other parameters revealed no significant differences. CONCLUSION:
The data of this study demonstrate a faster wound healing without the use of a
postoperative wound drain in primary total knee arthroplasty which is performed
without a tourniquet. Other parameters could not show any significant differences
thus indicating that a postoperative wound drain has no significant advantage and
the risk of a retrograde bacterial colonisation is well documented. Based on
these data we recommend performing a primary total knee arthroplasty without a
postoperative drain if the procedure is done without a tourniquet.
PMID- 25139716
TI - Prospective randomized trial comparing open reduction and internal fixation with
minimally invasive reduction and percutaneous fixation in managing displaced
intra-articular calcaneal fractures.
AB - PURPOSE: Managing displaced intra-articular calcaneal fractures remains
controversial. A prospective randomised trial was undertaken to compare open
reduction and internal fixation (ORIF) with minimally invasive reduction and
percutaneous fixation (MIRPF). METHODS: Forty-five displaced intra-articular
calcaneal fractures were randomised to undergo either ORIF (n = 23) or MIRPF (n =
22). Patients were followed up clinically and radiologically for a minimum of one
year postoperatively. The primary outcome measure was wound-healing complication.
Functional outcome was assessed using Creighton Nebraska Health Foundation (CNF)
scale, and radiological outcome was assessed using plain radiographs and computed
tomography (CT) scans. RESULTS: Of the 23 heels in the ORIF group, seven (30%)
had wound-healing problems, compared with none in the MIRPF group (p = 0.005).
There was no statistically significant difference in radiological outcomes
between groups, as measured by Bohler's angle, Gissane's angle and Score Analysis
of Verona (SAVE). Median time to return to work was two weeks earlier (p =
0.004), and the functional outcome score (CNF scale) at one year of follow-up was
better (p = 0.013) following MIRPF compared with ORIF. CONCLUSION: MIRPF is
associated with fewer wound-healing problems, better functional outcome and
earlier return to work compared with ORIF.
PMID- 25139717
TI - Cryoablation, limited fluoroscopy, and more.
PMID- 25139718
TI - The significance of oxygen during contact lens wear.
AB - In order to establish the relevance of oxygen to contemporary contact lens
practice, a review of the literature was conducted. The results indicate that
there are a number of processes occurring in the normal healthy eye where oxygen
is required and which are potentially affected by the presence of a contact lens.
These activities appear to take place at all corneal levels, as well as at the
limbus. Evidence from laboratory, clinical and modelling studies indicates that
what constitutes normal oxygenation (normoxia) depends on, among other things,
the physiological system under consideration, corneal location and the state of
eye closure. This diversity is reflected in the wide range of minimum lens oxygen
transmissibility (Dk/t) requirements that are present in a literature.
PMID- 25139719
TI - Power profiles of single vision and multifocal soft contact lenses.
AB - PURPOSE: The purpose of this study was to investigate the optical zone power
profile of the most commonly prescribed soft contact lenses to assess their
potential impact on peripheral refractive error and hence myopia progression.
METHODS: The optical power profiles of six single vision and ten multifocal
contact lenses of five manufacturers in the powers -1.00 D, -3.00 D, and -6.00 D
were measured using the SHSOphthalmic (Optocraft GmbH, Erlangen, Germany).
Instrument repeatability was also investigated. RESULTS: Instrument repeatability
was dependent on the distance from the optical centre, manifesting unreliable
data for the central 1mm of the optic zone. Single vision contact lens
measurements of -6.00 D lenses revealed omafilcon A having the most negative
spherical aberration, lotrafilcon A having the least. Somofilcon A had the
highest minus power and lotrafilcon A the biggest deviation in positive
direction, relative to their respective labelled powers. Negative spherical
aberration occurred for almost all of the multifocal contact lenses, including
the centre-distance designs etafilcon A bifocal and omafilcon A multifocal.
Lotrafilcon B and balafilcon A seem to rely predominantly on the spherical
aberration component to provide multifocality. CONCLUSIONS: Power profiles of
single vision soft contact lenses varied greatly, many having a negative
spherical aberration profile that would exacerbate myopia. Some lens types and
powers are affected by large intra-batch variability or power offsets of more
than 0.25 dioptres. Evaluation of power profiles of multifocal lenses was derived
that provides helpful information for prescribing lenses for presbyopes and
progressing myopes.
PMID- 25139720
TI - Scoring hip osteoarthritis with MRI (SHOMRI): A whole joint osteoarthritis
evaluation system.
AB - BACKGROUND: To develop a semi-quantitative MR-based hip osteoarthritis (OA)
evaluation system (Scoring hip osteoarthritis with MRI, SHOMRI), and to test its
reproducibility and face validity. METHODS: The study involved 98 subjects with
informed consent. Three-Tesla MR imaging of hip was performed in three planes
with intermediate-weighted fat saturated FSE sequences. Two radiologists assessed
cartilage loss, bone marrow edema pattern, subchondral cyst in 10 subregions, and
assessed labrum in 4 subregions. In addition, presence or absence of ligamentum
teres integrity, paralabral cysts, intra-articular body, and effusion in the hip
joint were analyzed using the SHOMRI system. The reproducibility was assessed
with intra-class correlation coefficient (ICC), Cohen's Kappa values and percent
agreement. SHOMRI scores were correlated with radiographic Kellgren-Lawrence (KL)
and OARSI atlas gradings, and clinical parameters, the hip osteoarthritis outcome
score (HOOS) and hip range of motion (ROM), using Spearman's rank correlation and
ordinal logistic regression. RESULTS: ICC values were in the excellent range,
0.91 to 0.97. Cohen's Kappa values and percent agreement ranged from 0.55 to 0.79
and 66 to 99%, respectively. SHOMRI demonstrated significant correlations with KL
and OARSI gradings as well as with clinical parameters, HOOS and ROM (P < 0.05).
Among the SHOMRI features, subchondral cyst and bone marrow edema pattern showed
the highest correlation with HOOS and ROM. CONCLUSION: SHOMRI demonstrated
moderate to excellent reproducibility and significant correlation with
radiographic gradings and clinical parameters.
PMID- 25139721
TI - Authors' reply to de Vries.
PMID- 25139722
TI - Male-specific use of the purr in the ring-tailed lemur (Lemur catta).
AB - In mammals, purring has been described in mostly affiliative contexts. In the
ring-tailed lemur (Lemur catta), both males and females purr, but only males were
observed purring in agonistic contexts. In order to determine whether male ring
tailed lemurs purr as aggressive displays during intrasexual agonistic
encounters, 480 h of focal data were collected on 25 adult males from Beza
Mahafaly Special Reserve, Madagascar, from March to July 2010. The male purring
rate increased during periods of male-male agonism when compared to times without
intrasexual agonism, and the purring rate was positively correlated with male
dominance rank. However, the purring rate was not significantly higher during
winning agonistic interactions when compared with losing encounters. My results
indicate that the male ring-tailed lemur purr is used most frequently as an
agonistic vocalization in male-male encounters, in addition to being used less
frequently in other social contexts, including during tail-waving at females,
resting, scent-marking, feeding and copulation. Dominant males have higher
purring rates across social situations, suggesting that the purring rate may be
driven by intrinsic male qualities rather than functioning as a meaningful signal
in each disparate social context. Male purring in intrasexual agonistic
encounters can be added to previously described social contexts for ring-tailed
lemur purring.
PMID- 25139723
TI - Patient and provider perspectives on Bedsider.org, an online contraceptive
information tool, in a low income, racially diverse clinic population.
AB - OBJECTIVE: To explore patient and provider perspectives regarding a new Web-based
contraceptive support tool. STUDY DESIGN: We conducted a qualitative study at an
urban Medicaid-based clinic among sexually active women interested in starting a
new contraceptive method, clinic providers and staff. All participants were given
the opportunity to explore Bedsider, an online contraceptive support tool
developed for sexually active women ages 18-29 by the National Campaign to
Prevent Teen and Unplanned Pregnancy and endorsed by the American Congress of
Obstetricians and Gynecologists. Focus groups were conducted separately among
patient participants and clinic providers/staff using open-ended structured
interview guides to identify specific themes and key concepts related to use of
this tool in an urban clinic setting. RESULTS: Patient participants were very
receptive to this online contraceptive support tool, describing it as
trustworthy, accessible and empowering. In contrast, clinic providers and staff
had concerns regarding the Website's legitimacy, accessibility, ability to
empower patients and applicability, which limited their willingness to recommend
its use to patients. CONCLUSION: Contrasting opinions regarding Bedsider may
point to a potential disconnect between how providers and patients view
contraception information tools. Further qualitative and quantitative studies are
needed to explore women's perspectives on contraceptive education and counseling
and providers' understanding of these perspectives. IMPLICATIONS STATEMENT: This
study identifies a contrast between how patients and providers in an urban clinic
setting perceive a Web-based contraceptive tool. Given a potential patient
provider discrepancy in preferred methods and approaches to contraceptive
counseling, additional research is needed to enhance this important arena of
women's health care.
PMID- 25139724
TI - Intrauterine lidocaine for pain control during laminaria insertion: a randomized
controlled trial.
AB - OBJECTIVE: To determine if intrauterine administration of 5 cc of 2% lidocaine in
addition to paracervical block reduces pain during laminaria insertion, when
compared with paracervical block and saline placebo. STUDY DESIGN: This was a
randomized, double blind placebo-controlled trial. Women presenting for abortion
by dilation and evacuation (D&E) at 14-24 weeks gestational age were randomized
to receive an intrauterine instillation of either 5 mL of 2% lidocaine or 5 mL of
normal saline, in addition to standard paracervical block with 20 cc of 0.25%
bupivacaine. Our primary outcome was self-reported pain scores on a 100mm Visual
Analogue Scale (VAS) immediately following laminaria insertion. Secondary outcome
was self-reported VAS pain score indicating the maximum level of pain experienced
during the 24-48-h interval between laminaria insertion and D&E procedure.
RESULTS: Seventy-two women were enrolled, and data for 67 women were analyzed,
only two of whom were more than 21 weeks on gestation. The range of pain scores
at both time points was large (1-90 mm at laminaria insertion; 0-100mm in
laminaria-D&E interval). Mean pain scores were not different between treatment
groups at laminaria insertion, (33 vs. 32, p=.8) or in the laminaria - D&E
interval (43 vs. 44, p=.9). CONCLUSION: Intrauterine administration of 5 cc of 2%
lidocaine in addition to paracervical block did not reduce pain with laminaria
insertion when compared to paracervical block with saline placebo. IMPLICATIONS:
Intrauterine lidocaine combined with paracervical block does not improve pain
control at laminaria insertion when compared with paracervical block and saline
placebo. Wide variation in pain scores and persistent pain after laminaria
insertion suggests patient would benefit from more effective methods of pain
control at laminaria insertion and during the post-laminaria interval.
PMID- 25139725
TI - Recent advances in the structure-based and ligand-based design of IKKbeta
inhibitors as anti-inflammation and anti-cancer agents.
AB - NF-kappaB is a significant transcription factor that regulates the expression of
various pro-survival genes. IKK is a crucial protein kinase that activates NF
kappaB translocating from cytoplasm to nucleus for DNA binding. It is composed of
three subunits, IKKalpha, IKKbeta, IKKgamma (NEMO), where IKKalpha and IKKbeta
are catalytic subunits, and IKKgamma is the regulatory subunit. Many diseases,
such as Hodgkin's disease, Hepatitis-associated hepatocellular carcinoma,
colorectal cancer, prostate cancer, rheumatoid arthritis and inflammatory bowel
disease, are related to IKK and NF-kappaB. So far, various IKK inhibitors
targeting the ATP binding site have been identified through high throughput
screening, rational design or in silico methods, however, only three of them (CHS
828, EB-1627 and IMD-1041) have been under clinical studies, indicating the
strategy for the design of IKK inhibitors need to be reinspected. Besides ATP
competitive inhibitors, several other inhibitors have also been disclosed
recently, which provide novel concepts to the discovery of IKK inhibitors. In
this review, we focus on two parts: 1) the chemotypes and binding patterns of the
traditional ATP-competitive IKK inhibitors; 2) novel strategies for the
identification of non-ATP-competitive IKK inhibitors as NF-kappaB modulators.
Through these discussions we hope to present inspirations for the development of
new IKK inhibitors.
PMID- 25139727
TI - Mindfulness-based intervention to treat insomnia in elderly people.
PMID- 25139726
TI - Rationale and design of REWARD (revving-up exercise for sustained weight loss by
altering neurological reward and drive): a randomized trial in obese endometrial
cancer survivors.
AB - BACKGROUND: Obesity is a leading risk factor for endometrial cancer (EC),
particularly Type I forms, which are increasing in the U.S. Although death rates
from most cancers have been decreasing, overall mortality in EC is increasing in
the U.S. EC survivors' poor fitness combined with their surgical treatments may
make weight loss particularly challenging. High intensity exercise increases
neurotrophins and neurological reward via altered striatal dopamine in animals,
and, in humans, chronic high intensity exercise enhances meal-induced satiety and
may reduce hedonic eating. "Assisted" exercise, a mode of exercise whereby a
patient's voluntary exercise rate is augmented mechanically, may modulate brain
dopamine levels in Parkinson's Disease patients but has not been previously
evaluated as a treatment for obesity. METHODS: We describe the rationale and
design of the REWARD trial, which has the overarching goal of randomizing 120
obese EC survivors to "assisted" or voluntary rate cycling to evaluate the
efficacy of "assisted" exercise in enhancing and sustaining weight loss. Patients
in both arms will receive 3 days/week of supervised exercise and 1 day/week of a
group dietary behavioral intervention for 16 weeks and, then, will be followed
for 6 months. OUTCOMES: The primary outcome is weight loss. Secondary outcomes
include measures for body composition, fitness, eating behavior, exercise
motivation and, quality of life as well as cognition and food reward and
motivation as assessed by functional magnetic resonance imaging (fMRI) tasks.
CONCLUSIONS: If successful, the REWARD program could be extended to help sustain
weight loss in obese cancer and non-cancer patients.
PMID- 25139728
TI - Enhancing physical and social environments to reduce obesity among public housing
residents: rationale, trial design, and baseline data for the Healthy Families
study.
AB - Intervention programs that change environments have the potential for greater
population impact on obesity compared to individual-level programs. We began a
cluster randomized, multi-component multi-level intervention to improve weight,
diet, and physical activity among low-socioeconomic status public housing
residents. Here we describe the rationale, intervention design, and baseline
survey data. After approaching 12 developments, ten were randomized to
intervention (n=5) or assessment-only control (n=5). All residents in
intervention developments are welcome to attend any intervention component:
health screenings, mobile food bus, walking groups, cooking demonstrations, and a
social media campaign; all of which are facilitated by community health workers
who are residents trained in health outreach. To evaluate weight and behavioral
outcomes, a subgroup of female residents and their daughters age 8-15 were
recruited into an evaluation cohort. In total, 211 households completed the
survey (RR=46.44%). Respondents were Latino (63%), Black (24%), and had <= high
school education (64%). Respondents reported <=2 servings of fruits &
vegetables/day (62%), visiting fast food restaurants 1+ times/week (32%), and
drinking soft drinks daily or more (27%). The only difference between randomized
groups was race/ethnicity, with more Black residents in the intervention vs.
control group (28% vs. 19%, p=0.0146). Among low-socioeconomic status urban
public housing residents, we successfully recruited and randomized families into
a multi-level intervention targeting obesity. If successful, this intervention
model could be adopted in other public housing developments or entities that also
employ community health workers, such as food assistance programs or hospitals.
PMID- 25139729
TI - Survival benefit of primary deceased donor transplantation with high-KDPI
kidneys.
AB - The Kidney Donor Profile Index (KDPI) has been introduced as an aid to evaluating
deceased donor kidney offers, but the relative benefit of high-KDPI kidney
transplantation (KT) versus the clinical alternative (remaining on the waitlist
until receipt of a lower KDPI kidney) remains unknown. Using time-dependent Cox
regression, we evaluated the mortality risk associated with high-KDPI KT (KDPI 71
80, 81-90 or 91-100) versus a conservative, lower KDPI approach (remain on
waitlist until receipt of KT with KDPI 0-70, 0-80 or 0-90) in first-time adult
registrants, adjusting for candidate characteristics. High-KDPI KT was associated
with increased short-term but decreased long-term mortality risk. Recipients of
KDPI 71-80 KT, KDPI 81-90 KT and KDPI 91-100 KT reached a "break-even point" of
cumulative survival at 7.7, 18.0 and 19.8 months post-KT, respectively, and had a
survival benefit thereafter. Cumulative survival at 5 years was better in all
three high-KDPI groups than the conservative approach (p < 0.01 for each
comparison). Benefit of high-KDPI KT was greatest in patients age >50 years and
patients at centers with median wait time >=33 months. Recipients of high-KDPI KT
can enjoy better long-term survival; a high-KDPI score does not automatically
constitute a reason to reject a deceased donor kidney.
PMID- 25139730
TI - Effects of ranibizumab on the extracellular matrix production by human Tenon's
fibroblast.
AB - Anti-Vascular Endothelial Growth Factors (Anti-VEGF) agents have received recent
interest as potential anti-fibrotic agents for their concurrent use with
trabeculectomy. Preliminary cohort studies have revealed improved bleb morphology
following trabeculectomy augmented with ranibizumab. The effects of this
humanized monoclonal antibody on human Tenon's fibroblast (HTF), the key player
of post trabeculectomy scar formation, are not fully understood. This study was
conducted to understand the effects of ranibizumab on extracellular matrix
production by HTF. The effect of ranibizumab on HTF proliferation and cell
viability was determined using MTT assay (3-(4,5-dimethylthiazone-2-yl)-2,5
diphenyl tetrazolium). Ranibizumab at concentrations ranging from 0.01 to 0.5
mg/mL were administered for 24, 48 and 72 h in serum and serum free conditions.
Supernatants and cell lysates from samples were assessed for collagen type 1
alpha 1 and fibronectin mRNA and protein level using quantitative real time
polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay
(ELISA). After 48-h, ranibizumab at 0.5 mg/mL, significantly induced cell death
under serum-free culture conditions (p < 0.05). Ranibizumab caused significant
reduction of collagen type 1 alpha 1 (COL1A1) mRNA, but not for fibronectin (FN).
Meanwhile, COL1A1 and FN protein levels were found upregulated in treated
monolayers compared to control monolayers. Ranibizumab at 0.5 mg/mL significantly
reduced cell viability in cultured HTF. From this study, we found that single
application of ranibizumab is inadequate to induce the anti-fibrotic effects on
HTF, suggesting the importance of adjunctive therapy. Further studies are
underway to understand mechanism of actions of ranibizumab on HTF.
PMID- 25139731
TI - Observation of interstitial molecular hydrogen in clathrate hydrates.
AB - The current knowledge and description of guest molecules within clathrate
hydrates only accounts for occupancy within regular polyhedral water cages.
Experimental measurements and simulations, examining the tert-butylamine + H2 +
H2O hydrate system, now suggest that H2 can also be incorporated within hydrate
crystal structures by occupying interstitial sites, that is, locations other than
the interior of regular polyhedral water cages. Specifically, H2 is found within
the shared heptagonal faces of the large (4(3)5(9)6(2)7(3)) cage and in cavities
formed from the disruption of smaller (4(4)5(4)) water cages. The ability of H2
to occupy these interstitial sites and fluctuate position in the crystal lattice
demonstrates the dynamic behavior of H2 in solids and reveals new insight into
guest-guest and guest-host interactions in clathrate hydrates, with potential
implications in increasing overall energy storage properties.
PMID- 25139732
TI - Hyperosmolar tears enhance cooling sensitivity of the corneal nerves in rats:
possible neural basis for cold-induced dry eye pain.
AB - PURPOSE: Tear hyperosmolarity is a ubiquitous feature of dry-eye disease.
Although dry-eye patients' sensitivity to cooling is well known, the effects of
tear hyperosmolarity on a small amount of cooling in the corneal nerves have not
been quantitatively examined. Recently reported corneal afferents, high-threshold
cold sensitive plus dry-sensitive (HT-CS + DS) neurons, in rats is normally
excited by strong (>4 degrees C) cooling of the cornea, which, when applied to
healthy humans, evokes the sensation of discomfort. However, corneal cooling
measured between blinks does not exceed 2 degrees C normally. Thus, we sought to
determine if these nociceptors could be sensitized by hyperosmolar tears such
that they are now activated by small cooling of the ocular surface. METHODS:
Trigeminal ganglion neurons innervating the cornea were extracellularly recorded
in isoflurane-anesthetized rats. The responses of single corneal neurons to
cooling stimuli presented in the presence of hyperosmolar (350-800 mOsm NaCl)
tears were examined. RESULTS: The HT-CS + DS neurons with thresholds averaging 4
degrees C cooling responded to cooling stimuli presented after 15 minutes of
hyperosmolar tears with thresholds of less than 1 degrees C. The response
magnitudes also were enhanced so that the responses to small (2 degrees C)
cooling emerged, where none was observed before. CONCLUSIONS: These results
demonstrate that after exposure to hyperosmolar tears, these nociceptive corneal
neurons now begin to respond to the slight cooling normally encountered between
blinks, enabling the painful information to be carried to the brain, which could
explain the cooling-evoked discomfort in dry eye patients.
PMID- 25139733
TI - NF-kappaB-mediated nitric oxide production and activation of caspase-3 cause
retinal ganglion cell death in the hypoxic neonatal retina.
AB - PURPOSE: Hypoxic insult to the developing retina results in apoptosis of retinal
ganglion cells (RGCs) through production of inflammatory mediators, nitric oxide
(NO), and free radicals. The present study was aimed at elucidating the pathway
through which hypoxia results in overproduction of NO in the immature retina, and
its role in causing apoptosis of RGCs. METHODS: Wistar rats (1 day old) were
exposed to hypoxia and their retinas were studied at 3 hours to 14 days after
exposure. The protein expression of nuclear factor-kappaB (NF-kappaB) and
neuronal nitric oxide synthase (nNOS) in the retina and primary cultures of RGCs
was analyzed using Western blotting and double-immunofluorescence, whereas the
concentration of NO was determined calorimetrically. In cultured RGCs, hypoxia
induced apoptosis was evaluated by caspase-3 immunolabeling. RESULTS: Following
hypoxic exposure, NF-kappaB-mediated expression of nNOS, which was localized to
the RGCs, and subsequent NO production was significantly increased in the
developing retina. In primary cultures of RGCs subjected to hypoxia, the
upregulation of nNOS and NO was significantly suppressed when treated with 7
nitroindazole (7-NINA), an nNOS inhibitor or BAY, an NF-kappaB inhibitor. Hypoxia
induced apoptosis of RGCs, which was evident with caspase-3 labeling, also was
suppressed when these cells were treated with 7-NINA or BAY. CONCLUSIONS: Our
results suggest that in RGCs, hypoxic induction of nNOS is mediated by NF-kappaB
and the resulting increased release of NO by RGCs causes their apoptosis through
caspase-3 activation. It is speculated that targeting nNOS could be a potential
neuroprotective strategy against hypoxia-induced RGCs death in the developing
retina.
PMID- 25139734
TI - Mesothelial cells: a cellular surrogate for tissue engineering of corneal
endothelium.
AB - PURPOSE: To evaluate whether mouse adipose tissue mesothelial cells (ATMCs) share
morphologic and biochemical characteristics with mouse corneal endothelial cells
(CECs) and to evaluate their capacity to adhere to the decellularized basal
membrane of human anterior lens capsules (HALCs) as a potential tissue-engineered
surrogate for corneal endothelium replacement. METHODS: Adipose tissue
mesothelial cells were isolated from the visceral adipose tissue of adult mice,
and their expression of several corneal endothelium markers was determined with
quantitative RT-PCR, immunofluorescence, and Western blotting. Adipose tissue
mesothelial cells were cultured in a mesothelial retaining phenotype medium
(MRPM) and further seeded and cultured on top of the decellularized basal
membrane of HALCs. ATMC-HALC composites were evaluated by optical microscopy,
immunofluorescence, and transmission electron microscopy. RESULTS: Mesothelial
retaining phenotype medium-cultured ATMCs express the corneal endothelium markers
COL4A2, COL8A2, SLC4A4, CAR2, sodium- and potassium-dependent adenosine
triphosphatase (Na(+)/K(+)-ATPase), beta-catenin, zona occludens-1, and N
cadherin in a pattern similar to that in mouse CECs. Furthermore, ATMCs displayed
strong adhesion capacity onto the basal membrane of HALCs and formed a confluent
monolayer within 72 hours of culture in MRPM. Ultrastructural morphologic and
marker characteristics displayed by ATMC monolayer on HALCs clearly indicated
that ATMCs retained their original phenotype of squamous epithelial-like cells.
CONCLUSIONS: Corneal endothelial cells and ATMCs share morphologic (structural)
and marker (functional) similarities [corrected]. The ATMCs adhered and formed
structures mimicking focal adhesion complexes with the HALC basal membrane.
Monolayer structure and achieved density of ATMCs support the proposal to use
adult human mesothelial cells (MCs) as a possible surrogate for damaged corneal
endothelium.
PMID- 25139735
TI - The external limiting membrane in early-onset Stargardt disease.
AB - PURPOSE: To describe pathologic changes of the external limiting membrane (ELM)
in young patients with early-onset Stargardt (STGD1) disease. METHODS: Twenty-six
STGD1 patients aged younger than 20 years with confirmed disease-causing
adenosine triphosphate-binding cassette, subfamily A, member 4 (ABCA4) alleles
and 30 age-matched unaffected individuals were studied. Spectral-domain optical
coherence tomography (SD-OCT), fundus autofluorescence (AF), and color fundus
photography (CFP) images, as well as full-field electroretinograms were obtained
and analyzed for one to four visits in each patient. RESULTS: The ELM in all
patients exhibited a distinct thickening that was not observed in unaffected
individuals. In addition, accumulations of reflective deposits were noted in the
outer nuclear layer in every patient. Four patients exhibited a concave
protuberance or bulging of a thickened and hyperreflective ELM band within the
fovea containing preserved photoreceptors. Longitudinal SD-OCT data in several
patients revealed the persistence of this ELM abnormality over a period of time
(1-4 years). Furthermore, the edges of the inner segment ellipsoid band appeared
to recede earlier than the ELM band in active lesions. CONCLUSIONS: Structural
changes seen in the ELM of this cohort may reflect a gliotic response to cellular
stress at the photoreceptor level in early-onset STGD1.
PMID- 25139736
TI - Anatomic changes in Schlemm's canal and collector channels in normal and primary
open-angle glaucoma eyes using low and high perfusion pressures.
AB - PURPOSE: To examine the anatomy of Schlemm's canal (SC) and collector channels
(CCs) in normal human and primary open-angle glaucoma (POAG) eyes under low and
high perfusion pressure. METHODS: In normal (n = 3) and POAG (n = 3) eye pairs,
one eye was perfused at 10 mm Hg while the fellow eye was perfused at 20 mm Hg
for 2 hours. Eyes were perfusion fixed at like pressures, dissected into
quadrants, embedded in Epon Araldite, and scanned by three-dimensional micro
computed tomography (3D micro-CT). Schlemm's canal volume, CC orifice area,
diameter, and number were measured using ANALYZE software. RESULTS: Normal eyes
showed a larger SC volume (3.3-fold) and CC orifice area (9962.8 vs. 8825.2
MUm(2)) and a similar CC diameter (34.3 +/- 17.8 vs. 32.7 +/- 13.0 MUm) at 10 mm
Hg compared to 20 mm Hg. In POAG eyes, SC volume (2.0-fold), CC orifice area
(8049.2 MUm(2)-6468.4 MUm(2)), and CC diameter (36.2 +/- 19.1 vs. 29.0 +/- 13.8
MUm) were increased in 10 mm Hg compared to 20 mm Hg perfusion pressures. Partial
and total CC occlusions were present in normal and POAG eyes, with a 3.7-fold
increase in total occlusions in POAG eyes compared to normal eyes at 20 mm Hg.
Visualization of CCs increased by 24% in normal and by 21% in POAG eyes at 20 mm
Hg compared to 10 mm Hg. Schlemm's canal volume, CC area, and CC diameter were
decreased in POAG eyes compared to normal eyes at like pressures. CONCLUSIONS:
Compensatory mechanisms for transient and short periods of increased pressure
appear to be diminished in POAG eyes. Variable response to pressure change in SC
and CCs may be a contributing factor to outflow facility change in POAG eyes.
PMID- 25139737
TI - CCR7 is critical for the induction and maintenance of Th17 immunity in dry eye
disease.
AB - PURPOSE: We characterized antigen-presenting cell (APC)-relevant chemokine
receptor expression in dry eye disease (DED), and investigated the effect of
topical CC chemokine receptor (CCR)-7 blockade specifically on Th17 cell immunity
and dry eye disease severity. METHODS: We induced DED in female C57BL/6 mice.
Chemokine receptor expression by corneal APCs was characterized using
immunohistochemistry. To determine the functional role of CCR7 in DED, mice were
treated topically with either anti-CCR7, a control isotype antibody, or left
untreated, and clinical disease severity, Th17 responses, and molecular markers
of DED were quantified. RESULTS: Frequencies of CD11b(+) cells and their
chemokine expression were increased in the cornea of DED mice. Mice treated
topically with anti-CCR7 antibody displayed a significant reduction in clinical
disease severity and Th17 response compared to the isotype and untreated groups.
Topical CCR7 blockade was effective in ameliorating DED in its acute and chronic
stages. CONCLUSIONS: Our findings suggest that CCR7-mediated trafficking of APCs
drives the induction and maintenance of Th17 immunity in DED and that CCR7
blockade is effective in suppressing the immunopathogenic mechanisms in DED.
PMID- 25139738
TI - HE3286 reduces axonal loss and preserves retinal ganglion cell function in
experimental optic neuritis.
AB - PURPOSE: Optic nerve inflammation, demyelination, and axonal loss are all
prominent features of optic neuritis. While corticosteroids hasten visual
recovery in optic neuritis, no treatment improves final visual outcomes. HE3286
(17alpha-ethynyl-5-androstene-3beta,7beta,17beta-triol), a synthetic derivative
of a natural steroid, beta-AET (5-androstene-3beta,7beta,17beta-triol), exerts
anti-inflammatory effects in several disease models and has purported
neuroprotective effects as well. HE3286's ability to suppress optic neuritis was
examined in experimental autoimmune encephalomyelitis (EAE), a model of multiple
sclerosis. METHODS: Experimental autoimmune encephalomyelitis was induced in
C57/BL6 mice. Mice were treated daily with intraperitoneal vehicle or 40 mg/kg
HE3286. Visual function was assessed by optokinetic responses (OKR) at baseline
and every 10 days until euthanasia at 40 days post immunization. Retinas and
optic nerves were isolated. Inflammation (hematoxylin and eosin and Iba1
staining), demyelination (Luxol fast blue staining), and axonal loss
(neurofilament staining) were assessed in optic nerve sections. Retinal ganglion
cells (RGCs) were immunolabeled with Brn3a antibodies to quantify RGC survival.
RESULTS: Progressive decreases in OKR occurred in vehicle-treated EAE mice, and
HE3286 treatment reduced the level of this vision loss. HE3286 also attenuated
the degree of inflammation, demyelination, and axonal loss in EAE optic nerves as
compared to nerves from vehicle-treated EAE mice. Retinal ganglion cell loss that
occurred in both vehicle- and HE3286-treated EAE mice was reduced in the temporal
retinal quadrant of HE3286-treated mice. CONCLUSIONS: HE3286 suppresses
inflammation, reduces demyelination and axonal loss, and promotes RGC survival
during experimental optic neuritis. Importantly, HE3286 treatment also preserves
some RGC function. Results suggest that HE3286 is a potential novel treatment for
optic neuritis.
PMID- 25139740
TI - A Phase IB multicentre dose-determination study of BHQ880 in combination with
anti-myeloma therapy and zoledronic acid in patients with relapsed or refractory
multiple myeloma and prior skeletal-related events.
AB - Dickkopf-1 (DKK1), expressed by myeloma cells, suppresses osteoblast function and
plays a key role in bone disease in multiple myeloma. BHQ880, a human
neutralizing IgG1 anti-DKK1 monoclonal antibody, is being investigated for its
impact on multiple myeloma-related bone disease and as an agent with potential
anti-myeloma activity. The primary objectives of this Phase IB study were to
determine the maximum tolerated dose (MTD) of BHQ880 and to characterize the dose
limiting toxicity (DLT) of escalating doses in combination with anti-myeloma
therapy and zoledronic acid. Twenty-eight patients were enrolled and received
BHQ880 at doses of 3-40 mg/kg. No DLTs were reported, therefore, the MTD was not
determined. The recommended Phase II dose was declared as 10 mg/kg, based mainly
on saturation data. There was a general trend towards increased bone mineral
density (BMD) observed over time; specific increases in spine BMD from Cycle 12
onwards irrespective of new skeletal-related events on study were observed, and
increases in bone strength at the spine and hip were also demonstrated in some
patients. BHQ880 in combination with zoledronic acid and anti-myeloma therapy was
well tolerated and demonstrated potential clinical activity in patients with
relapsed or refractory multiple myeloma.
PMID- 25139739
TI - Effects of negative stressors on DNA methylation in the brain: implications for
mood and anxiety disorders.
AB - Stress is a major contributor to anxiety and mood disorders. The recent discovery
of epigenetic changes in the brain resulting from stress has enhanced our
understanding of the mechanism by which stress is able to promote these
disorders. Although epigenetics encompasses chemical modifications that occur at
both DNA and histones, much attention has been focused on stress-induced DNA
methylation changes on behavior. Here, we review the effect of stress-induced DNA
methylation changes on physiological mechanisms that govern behavior and
cognition, dysregulation of which can be harmful to mental health. A literature
review was performed in the areas of DNA methylation, stress, and their impact on
the brain and psychiatric illness. Key findings center on genes involved in the
hypothalamic-pituitary-adrenal axis, neurotransmission and neuroplasticity. Using
animal models of different stress paradigms and clinical studies, we detail how
DNA methylation changes to these genes can alter physiological mechanisms that
influence behavior. Appropriate levels of gene expression in the brain play an
important role in mental health. This dynamic control can be disrupted by stress
induced changes to DNA methylation patterns. Advancement in other areas of
epigenetics, such as histone modifications and the discovery of the novel DNA
epigenetic mark, 5-hydroxymethylcytosine, could provide additional avenues to
consider when determining the epigenetic effects of stress on the brain.
PMID- 25139741
TI - Long-QT mutation p.K557E-Kv7.1: dominant-negative suppression of IKs, but
preserved cAMP-dependent up-regulation.
AB - AIMS: Mutations in KCNQ1, encoding for Kv7.1, the alpha-subunit of the IKs
channel, cause long-QT syndrome type 1, potentially predisposing patients to
ventricular tachyarrhythmias and sudden cardiac death, in particular, during
elevated sympathetic tone. Here, we aim at characterizing the p.Lys557Glu (K557E)
Kv7.1 mutation, identified in a Dutch kindred, at baseline and during (mimicked)
increased adrenergic tone. METHODS AND RESULTS: K557E carriers had moderate QTc
prolongation that augmented significantly during exercise. IKs characteristics
were determined after co-expressing Kv7.1-wild-type (WT) and/or K557E with minK
and Yotiao in Chinese hamster ovary cells. K557E caused IKs loss of function with
slowing of the activation kinetics, acceleration of deactivation kinetics, and a
rightward shift of voltage-dependent activation. Together, these contributed to a
dominant-negative reduction in IKs density. Confocal microscopy and western blot
indicated that trafficking of K557E channels was not impaired. Stimulation of WT
IKs by 3'-5'-cyclic adenosine monophosphate (cAMP) generated strong current up
regulation that was preserved for K557E in both hetero- and homozygosis.
Accumulation of IKs at fast rates occurred both in WT and in K557E, but was
blunted in the latter. In a computational model, K557E showed a loss of action
potential shortening during beta-adrenergic stimulation, in accordance with the
lack of QT shortening during exercise in patients. CONCLUSION: K557E causes IKs
loss of function with reduced fast rate-dependent current accumulation. cAMP
dependent stimulation of mutant IKs is preserved, but incapable of fully
compensating for the baseline current reduction, explaining the long QT intervals
at baseline and the abnormal QT accommodation during exercise in affected
patients.
PMID- 25139742
TI - Super-resolution imaging reveals that loss of the C-terminus of connexin43 limits
microtubule plus-end capture and NaV1.5 localization at the intercalated disc.
AB - AIMS: It is well known that connexin43 (Cx43) forms gap junctions. We recently
showed that Cx43 is also part of a protein-interacting network that regulates
excitability. Cardiac-specific truncation of Cx43 C-terminus (mutant
'Cx43D378stop') led to lethal arrhythmias. Cx43D378stop localized to the
intercalated disc (ID); cell-cell coupling was normal, but there was significant
sodium current (INa) loss. We proposed that the microtubule plus-end is at the
crux of the Cx43-INa relation. Yet, specific localization of relevant molecular
players was prevented due to the resolution limit of fluorescence microscopy.
Here, we use nanoscale imaging to establish: (i) the morphology of clusters
formed by the microtubule plus-end tracking protein 'end-binding 1' (EB1), (ii)
their position, and that of sodium channel alpha-subunit NaV1.5, relative to N
cadherin-rich sites, and (iii) the role of Cx43 C-terminus on the above-mentioned
parameters and on the location-specific function of INa. METHODS AND RESULTS:
Super-resolution fluorescence localization microscopy in murine adult
cardiomyocytes revealed EB1 and NaV1.5 as distinct clusters preferentially
localized to N-cadherin-rich sites. Extent of co-localization decreased in
Cx43D378stop cells. Macropatch and scanning patch clamp showed reduced INa
exclusively at cell end, without changes in unitary conductance. Experiments in
Cx43-modified HL1 cells confirmed the relation between Cx43, INa, and
microtubules. CONCLUSIONS: NaV1.5 and EB1 localization at the cell end is Cx43
dependent. Cx43 is part of a molecular complex that determines capture of the
microtubule plus-end at the ID, facilitating cargo delivery. These observations
link excitability and electrical coupling through a common molecular mechanism.
PMID- 25139743
TI - Glyoxalase 1 overexpression does not affect atherosclerotic lesion size and
severity in ApoE-/- mice with or without diabetes.
AB - AIMS: Advanced glycation end-products (AGEs) and their precursors have been
associated with the development of atherosclerosis. We recently discovered that
glyoxalase 1 (GLO1), the major detoxifying enzyme for AGE precursors, is
decreased in ruptured human plaques, and that levels of AGEs are higher in
rupture-prone plaques. We here investigated whether overexpression of human GLO1
in ApoE(-/-) mice could reduce the development of atherosclerosis. METHODS AND
RESULTS: We crossed C57BL/6 ApoE(-/-) mice with C57BL/6 GLO1 overexpressing mice
(huGLO1(+/-)) to generate ApoE(-/-) (n = 16) and ApoE(-/-) huGLO1(+/-) (n = 20)
mice. To induce diabetes, we injected a subset with streptozotocin (STZ) to
generate diabetic ApoE(-/-) (n = 8) and ApoE(-/-) huGLO1(+/-) (n = 13) mice. All
mice were fed chow and sacrificed at 25 weeks of age. The GLO1 activity was three
fold increased in huGLO1(+/-) aorta, but aortic root lesion size and phenotype
did not differ between mice with and without huGLO1(+/-) overexpression. We
detected no differences in gene expression in aortic arches, in AGE levels and
cytokines, in circulating cells, and endothelial function between ApoE(-/-) mice
with and without huGLO1(+/-) overexpression. Although diabetic mice showed
decreased GLO1 expression (P < 0.05) and increased lesion size (P < 0.05) in
comparison with non-diabetic mice, GLO1 overexpression also did not affect the
aortic root lesion size or inflammation in diabetic mice. CONCLUSION: In ApoE(-/
) mice with or without diabetes, GLO1 overexpression did not lead to decreased
atherosclerotic lesion size or systemic inflammation. Increasing GLO1 levels does
not seem to be an effective strategy to reduce glycation in atherosclerotic
lesions, likely due to increased AGE formation through GLO1-independent
mechanisms.
PMID- 25139744
TI - The cellular prion protein counteracts cardiac oxidative stress.
AB - AIMS: The cellular prion protein, PrP(C), whose aberrant isoforms are related to
prion diseases of humans and animals, has a still obscure physiological function.
Having observed an increased expression of PrP(C) in two in vivo paradigms of
heart remodelling, we focused on isolated mouse hearts to ascertain the capacity
of PrP(C) to antagonize oxidative damage induced by ischaemic and non-ischaemic
protocols. METHODS AND RESULTS: Hearts isolated from mice expressing PrP(C) in
variable amounts were subjected to different and complementary oxidative
perfusion protocols. Accumulation of reactive oxygen species, oxidation of
myofibrillar proteins, and cell death were evaluated. We found that overexpressed
PrP(C) reduced oxidative stress and cell death caused by post-ischaemic
reperfusion. Conversely, deletion of PrP(C) increased oxidative stress during
both ischaemic preconditioning and perfusion (15 min) with H2O2. Supporting its
relation with intracellular systems involved in oxidative stress, PrP(C) was
found to influence the activity of catalase and, for the first time, the
expression of p66(Shc), a protein implicated in oxidative stress-mediated cell
death. CONCLUSIONS: Our data demonstrate that PrP(C) contributes to the cardiac
mechanisms antagonizing oxidative insults.
PMID- 25139745
TI - Scrib:Rac1 interactions are required for the morphogenesis of the ventricular
myocardium.
AB - AIMS: The organization and maturation of ventricular cardiomyocytes from the
embryonic to the adult form is crucial for normal cardiac function. We have shown
that a polarity protein, Scrib, may be involved in regulating the early stages of
this process. Our goal was to establish whether Scrib plays a cell autonomous
role in the ventricular myocardium, and whether this involves well-known polarity
pathways. METHODS AND RESULTS: Deletion of Scrib in cardiac precursors utilizing
Scrib(flox) mice together with the Nkx2.5-Cre driver resulted in disruption of
the cytoarchitecture of the forming trabeculae and ventricular septal defects.
Although the majority of mice lacking Scrib in the myocardium survived to
adulthood, they developed marked cardiac fibrosis. Scrib did not physically
interact with the planar cell polarity (PCP) protein, Vangl2, in early
cardiomyocytes as it does in other tissues, suggesting that the anomalies did not
result from disruption of PCP signalling. However, Scrib interacted with Rac1
physically in embryonic cardiomyocytes and genetically to result in ventricular
abnormalities, suggesting that this interaction is crucial for the development of
the early myocardium. CONCLUSIONS: The Scrib-Rac1 interaction plays a crucial
role in the organization of developing cardiomyocytes and formation of the
ventricular myocardium. Thus, we have identified a novel signalling pathway in
the early, functioning, heart muscle. These data also show that the foetus can
recover from relatively severe abnormalities in prenatal ventricular development,
although cardiac fibrosis can be a long-term consequence.
PMID- 25139746
TI - Nitric oxide and protein kinase G act on TRPC1 to inhibit 11,12-EET-induced
vascular relaxation.
AB - AIMS: Vascular endothelial cells synthesize and release vasodilators such as
nitric oxide (NO) and epoxyeicosatrienoic acids (EETs). NO is known to inhibit
EET-induced smooth muscle hyperpolarization and relaxation. This study
investigates the underlying mechanism of this inhibition. METHODS AND RESULTS:
Through measurements of membrane potential and arterial tension, we show that
11,12-EET induced membrane hyperpolarization and vascular relaxation in
endothelium-denuded porcine coronary arteries. These responses were suppressed by
S-nitroso-N-acetylpenicillamine (SNAP) and 8-Br-cGMP, an NO donor and a membrane
permeant analogue of cGMP, respectively. The inhibitory actions of SNAP and 8-Br
cGMP on 11,12-EET-induced membrane hyperpolarization and vascular relaxation were
reversed by hydroxocobalamin, an NO scavenger; ODQ, a guanylyl cyclase inhibitor;
and KT5823, a protein kinase G (PKG) inhibitor. The inhibitory actions of SNAP
and 8-bromo cyclic GMP (8-Br-cGMP) on the EET responses were also abrogated by
shielding TRPC1-PKG phosphorylation sites with an excessive supply of exogenous
PKG substrates, TAT-TRPC1(S172) and TAT-TRPC1(T313). Furthermore, a
phosphorylation assay demonstrated that PKG could directly phosphorylate TRPC1 at
Ser(172) and Thr(313). In addition, 11,12-EET failed to induce membrane
hyperpolarization and vascular relaxation when TRPV4, TRPC1, or KCa1.1 was
selectively inhibited. Co-immunoprecipitation studies demonstrated that TRPV4,
TRPC1, and KCa1.1 physically associated with each other in smooth muscle cells.
CONCLUSION: Our findings demonstrate a novel role of the NO-cGMP-PKG pathway in
the inhibition of 11,12-EET-induced smooth muscle hyperpolarization and
relaxation via PKG-mediated phosphorylation of TRPC1.
PMID- 25139747
TI - Ranolazine prevents INaL enhancement and blunts myocardial remodelling in a model
of pulmonary hypertension.
AB - AIMS: Pulmonary arterial hypertension (PAH) reflects abnormal pulmonary vascular
resistance and causes right ventricular (RV) hypertrophy. Enhancement of the late
sodium current (INaL) may result from hypertrophic remodelling. The study tests
whether: (i) constitutive INaL enhancement may occur as part of PAH-induced
myocardial remodelling; (ii) ranolazine (RAN), a clinically available INaL
blocker, may prevent constitutive INaL enhancement and PAH-induced myocardial
remodelling. METHODS AND RESULTS: PAH was induced in rats by a single
monocrotaline (MCT) injection [60 mg/kg intraperitoneally (i.p.)]; studies were
performed 3 weeks later. RAN (30 mg/kg bid i.p.) was administered 48 h after MCT
and washed-out 15 h before studies. MCT increased RV systolic pressure and caused
RV hypertrophy and loss of left ventricular (LV) mass. In the RV, collagen was
increased; myocytes were enlarged with T-tubule disarray and displayed myosin
heavy chain isoform switch. INaL was markedly enhanced; diastolic Ca(2+) was
increased and Ca(2+) release was facilitated. K(+) currents were down-regulated
and APD was prolonged. In the LV, INaL was enhanced to a lesser extent and cell
Ca(2+) content was strongly depressed. Electrical remodelling was less prominent
than in the RV. RAN completely prevented INaL enhancement and limited most
aspects of PAH-induced remodelling, but failed to affect in vivo contractile
performance. RAN blunted the MCT-induced increase in RV pressure and medial
thickening in pulmonary arterioles. CONCLUSION: PAH induced remodelling with
chamber-specific aspects. RAN prevented constitutive INaL enhancement and blunted
myocardial remodelling. Partial mechanical unloading, resulting from an
unexpected effect of RAN on pulmonary vasculature, might contribute to this
effect.
PMID- 25139748
TI - Angiogenesis and remodelling in human thoracic aortic aneurysms.
AB - AIMS: Human thoracic aneurysm of the ascending aorta (TAA) is a chronic disease
characterized by dilatation of the aortic wall, which can progress to vessel
dissection and rupture. TAA has several aetiologies, but all forms present common
features, including tissue remodelling. Here, we determined and characterized the
angiogenic process associated with TAA and its relation with wall remodelling.
METHODS AND RESULTS: Immunostaining for blood vessels showed an increased density
of microvessels originating from the adventitia in the external medial layer of
TAA compared with healthy aortas. Proteomic array analysis of 55 angiogenic
factors in medial and adventitial layers showed different expression profiles in
both tissue compartments between aneurysmal and healthy aortas. Quantification by
ELISA confirmed that all forms of TAA contained higher levels of several pro- and
anti-angiogenic factors, including angiopoietin-1 and -2, fibroblast growth
factor-acidic, and thrombospondin-1, than that of healthy aortas. However, all
groups showed comparable levels of vascular endothelial growth factor-A.
Quantitative RT-PCR demonstrated that angiopoietins were overexpressed in TAA
media. Immunostaining and electron microscopy revealed that neovessels had
defective endothelial junctions and poor mural cell coverage. This incomplete
structure was associated with the accumulation of plasminogen and albumin in the
media of TAA. CONCLUSION: We describe, for the first time, leaky neovessel
formation in TAA media in association with an imbalance of angiogenic factor
levels. Although the initiating mechanisms of neo-angiogenesis in TAA and the
potential aetiology-related differences remain to be determined, our results
suggest that neo-angiogenesis could participate in TAA wall remodelling and
weakening through deposition of blood-borne zymogens.
PMID- 25139749
TI - Evaluation of the oxidative status in Oreochromis niloticus fed with tuna by
product meal: possible human health impact.
AB - The influence of tuna by-product meal (TBM) diets on the activities of
antioxidant enzymes in the muscles, gill and kidney of tilapia was evaluated. The
control diet (A0) used fish meal (FM) as the sole source of animal protein and
the other three diets (A10-A30), 33%-100% of FM was substituted by TBM at 10%
increments. The cytotoxicity of liver and muscles cytosol extracts in human liver
cell HepG2 was undertaken. The activities of glutathione S-transferase,
superoxide dismutase, catalase and TBARS values in the kidney of fish fed with
diet A30 were significantly different (p<0.05) and no alterations were observed
in muscle and gill anti-oxidant activities. Our study has confirmed that the
cytosol extract does not exhibit cytotoxic effects on the HepG2 cells. These
results indicate that the use of TBM as a total replacement for FM into tilapia
diets seems to have oxidative stress, thus generating effect on fish metabolism.
PMID- 25139750
TI - Hierarchical sampling for metastable conformers determines biomolecular
recognition: the case of malectin and diglucosylated N-glycan interactions.
AB - Structural information over the entire course of binding interactions based on
the analyses of energy landscapes is described, which provides a framework to
understand the events involved during biomolecular recognition. Conformational
dynamics of malectin's exquisite selectivity for diglucosylated N-glycan (Dig-N
glycan), a highly flexible oligosaccharide comprising of numerous dihedral
torsion angles, are described as an example. For this purpose, a novel approach
based on hierarchical sampling for acquiring metastable molecular conformations
constituting low-energy minima for understanding the structural features involved
in a biologic recognition is proposed. For this purpose, four variants of
principal component analysis were employed recursively in both Cartesian space
and dihedral angles space that are characterized by free energy landscapes to
select the most stable conformational substates. Subsequently, k-means clustering
algorithm was implemented for geometric separation of the major native state to
acquire a final ensemble of metastable conformers. A comparison of malectin
complexes was then performed to characterize their conformational properties.
Analyses of stereochemical metrics and other concerted binding events revealed
surface complementarity, cooperative and bidentate hydrogen bonds, water-mediated
hydrogen bonds, carbohydrate-aromatic interactions including CH-pi and stacking
interactions involved in this recognition. Additionally, a striking structural
transition from loop to beta-strands in malectin CRD upon specific binding to Dig
N-glycan is observed. The interplay of the above-mentioned binding events in
malectin and Dig-N-glycan supports an extended conformational selection model as
the underlying binding mechanism.
PMID- 25139751
TI - Synthesis and structure-activity relationships of novel, potent, orally active
hypoxia-inducible factor-1 inhibitors.
AB - Hypoxia-inducible factor-1 (HIF-1) is the chief transcription factor regulating
hypoxia-driven gene expression. HIF-1 overexpression is associated with poor
prognosis in several cancers and therefore represents an attractive target for
novel antitumor agents. We explored small molecule inhibitors of the HIF-1
pathway. Using high-throughput-screening, we identified benzanilide compound 1
(IC50=560 nM) as a seed. Subsequent extensive derivatization led to the discovery
of compounds 43a and 51d, with anti-HIF-1 activities in vitro (IC50=21 and 0.47
nM, respectively), and in vivo. Additionally, 43a (12.5-100mg/kg) also displayed
in vivo anti-tumor efficacy, without influencing body weight.
PMID- 25139752
TI - Coevolution of caudal skeleton and tail feathers in birds.
AB - Birds are capable of a wide range of aerial locomotor behaviors in part because
of the derived structure and function of the avian tail. The tail apparatus
consists of a several mobile (free) caudal vertebrae, a terminal skeletal element
(the pygostyle), and an articulated fan of tail feathers that may be spread or
folded, as well as muscular and fibroadipose structures that facilitate tail
movements. Morphological variation in both the tail fan and the caudal skeleton
that supports it are well documented. The structure of the tail feathers and the
pygostyle each evolve in response to functional demands of differing locomotor
behaviors. Here, I test whether the integument and skeleton coevolve in this
important locomotor module. I quantified feather and skeletal morphology in a
diverse sample of waterbirds and shorebirds using a combination of linear and
geometric morphometrics. Covariation between tail fan shape and skeletal
morphology was then tested using phylogenetic comparative methods. Pygostyle
shape is found to be a good predictor of tail fan shape (e.g., forked,
graduated), supporting the hypothesis that the tail fan and the tail skeleton
have coevolved. This statistical relationship is used to reconstruct feather
morphology in an exemplar fossil waterbird, Limnofregata azygosternon. Based on
pygostyle morphology, this taxon is likely to have exhibited a forked tail fan
similar to that of its extant sister clade Fregata, despite differing in inferred
ecology and other aspects of skeletal anatomy. These methods may be useful in
reconstructing rectricial morphology in other extinct birds and thus assist in
characterizing the evolution of flight control surfaces in birds.
PMID- 25139753
TI - Plasma estrone sulfate, clinical biochemistry, and milk yield of dairy cows
carrying a fetus from a bull or its clone.
AB - The aim of this article was to compare plasma estrone sulfate (E1SO4), clinical
biochemistry, and milk yield of dairy cows carrying a female fetus from a bull
(BULL) or from its clone (CLONE), evaluating also the relationship between the
former variables and the birth weight of the newborn. Sixteen recipient dairy
Friesian heifers (10 BULL and 7 CLONE) received a female embryo, obtained by in
vitro embryo production and sexing by polymerase chain reaction with the semen of
the BULL or the CLONE. Blood samples on all cows were obtained before feed
distribution in the morning from jugular vein from 4 weeks before to 4 weeks
after calving, to be analyzed for metabolic profile. The samples from late
gestation were also analyzed for E1SO4 concentration. To separately assess the
effect of calf birth weight (CBW), data were categorized as follows: low (<39 kg;
BWT-A), mid (39-46 kg; BWT-B), and high (>46 kg; BWT-C). The plasma
concentrations of beta-hydroxybutyric acid (BHB, P=0.019), Na (P=0.002), Cl
(P=0.026), strong cation-anion balance (P=0.020), total bilirubin (P=0.054), and
alpha1-globulin (P=0.044) were higher in prepartum BULL recipients than those in
CLONE, whereas BHB (P=0.021) and Mg (P=0.090) were higher in postpartum BULL
recipients, while no differences were recorded in the remaining postpartum
parameters. The CBW class had significant interaction with week of gestation on
antepartum plasma estrone sulfate (P=0.021), whereas CBW per se affected
antepartum plasma BHB (P=0.021), and nonesterified fatty acids (NEFA; P=0.011)
being higher in BWT-C which also had the lower NEFA concentration during
postpartum. Milk yield was unaffected by the sire used, both for quantitative and
qualitative aspects. Cows carrying heavier fetus (BWT-C) had a different
lactation affected by month compared with the other 2 CBW groups. From these
results, there were no differences between BULL and CLONE recipients. Estrone
sulfate, BHB, and NEFA may be used to predict CBW and provide different
nutritional management during gestation.
PMID- 25139754
TI - Relationship between macrophages in mouse uteri and angiogenesis in endometrium
during the peri-implantation period.
AB - The objective of this study is to examine the change in macrophage numbers,
inducible form of NO synthase (iNOS), and vascular endothelial growth factor
(VEGF) expression both before and after embryo implantation in the uterine tissue
of mice. In order to explore the mechanism of macrophages in endometrial
angiogenesis, 8-week-old female mice were divided into three groups: pregnant
group, pseudopregnant group (mated to male mice that had been vasectomized), and
estrous group (unmated). Individuals from these three groups were sacrificed at
time intervals D1.5 to D6.5. Formalin-fixed paraffin-embedded tissue was used for
immunocytochemical localization of Mphi, iNOS, and VEGF utilizing standard
methodology. The proportion of macrophages in the peripheral blood was determined
by flow cytometry, and the relationship between macrophage, iNOS, and VEGF
expression was analyzed. The proportion of peripheral blood macrophages in the
pregnancy group was significantly higher than that in the other groups. The
results of immunohistochemistry determined that the macrophages exhibited changes
in both numbers and distribution. The number of macrophages in the endometrium of
the pregnancy and pseudopregnancy groups was significantly higher than that in
the control (estrous) group. In the pregnancy group, macrophage numbers
dramatically decreased and gradually transferred to the perimetrium on D4.5.
Immunostaining revealed strong staining in the pregnancy group and weaker
staining in the pseudopregnant and control groups for both iNOS and VEGF. There
was strong, dense immunostaining at the implantation site for both iNOS and VEGF,
whereas light immunostaining was seen in interimplantation tissues on D5.5 to
D6.5. In the pregnant group, peripheral blood and uterine macrophage proportions
were negatively correlated, whereas the amount of macrophages, iNOS, and VEGF
expression in the endometrium were positively correlated. The expression of iNOS
and VEGF in the endometrium also displayed a strong positive correlation. In
conclusion, during embryo implantation, macrophages levels decreased in the
uterus, whereas the number of peripheral macrophages increased, suggesting that
macrophages may migrate into the peripheral blood and uterus to adapt for
pregnancy. Additionally, an increase in the expression of iNOS and VEGF was
observed during the implantation window, implying that iNOS and VEGF may play an
important role in promoting embryo implantation. The positive correlation between
macrophages, iNOS, and VEGF in the implanting uterus implied that macrophages
might regulate iNOS and VEGF during the implantation process.
PMID- 25139755
TI - Influence of stimulation by electroejaculation on myocardial function, acid-base
and electrolyte status, and hematobiochemical profiles in male dromedary camels.
AB - This study was carried out to evaluate the effect of electroejaculation (EEJ) on
myocardial function, acid-base balance, and hematobiochemical profiles in male
dromedary camels. Twenty sexually mature, apparently healthy male camels were
assigned to EEJ. Parallel, eight naturally mated male camels were enrolled as a
control group. Three blood samples were collected from each camel: just before
(T0), directly after (T1), and 24 hours after (T2) EEJ or natural mating. The
serum concentrations of the cardiac biomarker troponin I (cTnI), blood gas
parameters, and hematobiochemical profiles were determined. Nineteen camels were
ejaculated by the end of the second circuit and one by the end of the first
circuit. In both groups, the mean heart and respiratory rates had increased
significantly immediately after the procedure, but returned to normal values 24
hours after the procedure. The mean serum concentration of cTnI had increased
significantly in all camels after EEJ, but not in controls. However, at 24 hours
post-EEJ, the serum concentration of cTnI did not differ significantly compared
with baseline values. The blood pH and base excess had decreased, and the PCO2
and lactic acid had increased after EEJ. The EEJ provoked decreases in hematocrit
and mean corpuscular volume. In the control group, the base excess, HCO3(-),
TCO2, anion gap, and lactic acid increased slightly after mating but did not
reach a significant level compared with premating values. It is concluded that
EEJ in camels results in a reversible myocardial injury, changes in the acid-base
status, and increase the lactic acid concentration.
PMID- 25139756
TI - Importance of intense male sexual behavior for inducing the preovulatory LH surge
and ovulation in seasonally anovulatory female goats.
AB - The present study was carried out to determine whether the presence of
photostimulated sedated male goats could stimulate the LH preovulatory surge and
ovulation in seasonal anestrous goats. Sexually experienced male goats were
treated with artificial long days (16 hours light per day) from 1 November to 15
January to stimulate their sexual activity in March and April, corresponding to
the natural sexual rest. A female group of goats (n=20) was exposed to non
sedated males who displayed an intense sexual behavior and provided strong odor
(non-sedated group). Another female group of goats (n=20) was exposed to the
photo-stimulated male goats, but these males were sedated with Xylazine 2% to
prevent the expression of sexual behavior (sedated group). The sedated males also
provided a strong odor. Females of both groups had full physical and visual
contact with non-sedated or sedated males. In both groups, the males remained
with females during 4 days. The LH preovulatory surge of 10 female goats per
group was measured by determination of LH plasma concentrations in samples taken
every 3 hours. In addition, in all goats, (n=20 by group), ovulation was
determined by measuring plasma concentrations of progesterone. The proportion of
female goats showing a preovulatory LH surge was higher in goats exposed to non
sedated (10/10) than in those exposed to sedated bucks (0/10; P<0.0001).
Similarly, most of does in contact with non-sedated males ovulated (19/20), but
none of those in contact with sedated males did so (0/20; P<0.0001). We conclude
that the expression of an intense sexual behavior by male goats is necessary to
induce LH preovulatory surge and ovulation in seasonally anovulatory goats.
PMID- 25139757
TI - Novel hinge-binding motifs for Janus kinase 3 inhibitors: a comprehensive
structure-activity relationship study on tofacitinib bioisosteres.
AB - The Janus kinases (JAKs) are a family of cytosolic tyrosine kinases crucially
involved in cytokine signaling. JAKs have been demonstrated to be valid targets
in the treatment of inflammatory and myeloproliferative disorders, and two
inhibitors, tofacitinib and ruxolitinib, recently received their marketing
authorization. Despite this success, selectivity within the JAK family remains a
major issue. Both approved compounds share a common 7H-pyrrolo[2,3-d]pyrimidine
hinge binding motif, and little is known about modifications tolerated at this
heterocyclic core. In the current study, a library of tofacitinib bioisosteres
was prepared and tested against JAK3. The compounds possessed the tofacitinib
piperidinyl side chain, whereas the hinge binding motif was replaced by a variety
of heterocycles mimicking its pharmacophore. In view of the promising
expectations obtained from molecular modeling, most of the compounds proved to be
poorly active. However, strategies for restoring activity within this series of
novel chemotypes were discovered and crucial structure-activity relationships
were deduced. The compounds presented may serve as starting point for developing
novel JAK inhibitors and as a valuable training set for in silico models.
PMID- 25139758
TI - Effects of the biosynthesis and signaling pathway of ecdysterone on silkworm
(Bombyx mori) following exposure to titanium dioxide nanoparticles.
AB - Silkworm (Bombyx mori), a model Lepidoptera insect, is economically important.
Its growth and development are regulated by endogenous hormones. During the
process of transition from larvae to pupae, 20-hydroxyecdysone (20E) plays an
important role. The recent surge in consumer products and applications using
metallic nanoparticles has increased the possibility of human or ecosystem
exposure due to their unintentional release into the environment. We investigated
the effects of exposure to titanium dioxide nanoparticles (TiO2 NPs) on the
action of 20E in B. mori. Titanium dioxide nanoparticle treatment shortened the
molting duration by 8 hr and prolonged the molting peak period by 10 %. Solexa
sequencing profiled the changes in gene expression in the brain of fifth-instar
B. mori in response to TiO2NPS exposure for 72 hr, to address the effects on
hormone metabolism and regulation. Thirty one genes were differentially
expressed. The transcriptional levels of pi3k and P70S6K, which are involved in
the target of the rapamycin (TOR) signaling pathway, were up-regulated.
Transcriptional levels of four cytochrome P450 genes, which are involved in 20E
biosynthesis, at different developmental stages (48, 96, 144, and 192 hr) at 5th
instars of all displayed trends of increasing expression. Simultaneously, the
ecdysterone receptors, also displayed increasing trends. The 20E titers at four
developmental stages during the 5th instar were 1.26, 1.23, 1.72, and 2.16 fold
higher, respectively, than the control group. These results indicate that feeding
B. mori with TiO2 NPs stimulates 20E biosynthesis, shortens the developmental
progression, and reduces the duration of molting. Thus, application of TiO2 NPs
is of high significance for saving the labor force in sericulture, and our
research provides a reference for the ecological problems in the field of
Lepidoptera exposured to titanium dioxide nanoparticles.
PMID- 25139759
TI - Associations between liver enzymes, psychopathological and clinical features in
eating disorders.
AB - Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
levels are frequently reported in patients with anorexia nervosa (AN) and in
subjects who are overweight or with hyperlipidemia, which can be found to be
associated with binge eating disorder (BED) and bulimia nervosa (BN). Liver
functioning and psychopathological features have been evaluated in 43 patients
with AN, 33 with BN, and 32 with BED. Body mass index was found to be inversely
associated with AST and ALT in AN, and directly associated with AST and ALT in
BED. A positive association between ALT and AST and body shape concern in AN was
observed. Liver enzymes could be considered as an index of severity in AN and BED
patients.
PMID- 25139760
TI - Colloidal crystal grain boundary formation and motion.
AB - The ability to assemble nano- and micro- sized colloidal components into highly
ordered configurations is often cited as the basis for developing advanced
materials. However, the dynamics of stochastic grain boundary formation and
motion have not been quantified, which limits the ability to control and anneal
polycrystallinity in colloidal based materials. Here we use optical microscopy,
Brownian Dynamic simulations, and a new dynamic analysis to study grain boundary
motion in quasi-2D colloidal bicrystals formed within inhomogeneous AC electric
fields. We introduce "low-dimensional" models using reaction coordinates for
condensation and global order that capture first passage times between critical
configurations at each applied voltage. The resulting models reveal that equal
sized domains at a maximum misorientation angle show relaxation dominated by
friction limited grain boundary diffusion; and in contrast, asymmetrically sized
domains with less misorientation display much faster grain boundary migration due
to significant thermodynamic driving forces. By quantifying such dynamics vs.
compression (voltage), kinetic bottlenecks associated with slow grain boundary
relaxation are understood, which can be used to guide the temporal assembly of
defect-free single domain colloidal crystals.
PMID- 25139761
TI - Revisiting the adaptive and maladaptive effects of crossmodal plasticity.
AB - One of the most striking demonstrations of experience-dependent plasticity comes
from studies of sensory-deprived individuals (e.g., blind or deaf), showing that
brain regions deprived of their natural inputs change their sensory tuning to
support the processing of inputs coming from the spared senses. These mechanisms
of crossmodal plasticity have been traditionally conceptualized as having a
double-edged sword effect on behavior. On one side, crossmodal plasticity is
conceived as adaptive for the development of enhanced behavioral skills in the
remaining senses of early-deaf or blind individuals. On the other side,
crossmodal plasticity raises crucial challenges for sensory restoration and is
typically conceived as maladaptive since its presence may prevent optimal
recovery in sensory-re-afferented individuals. In the present review we stress
that this dichotomic vision is oversimplified and we emphasize that the notions
of the unavoidable adaptive/maladaptive effects of crossmodal reorganization for
sensory compensation/restoration may actually be misleading. For this purpose we
critically review the findings from the blind and deaf literatures, highlighting
the complementary nature of these two fields of research. The integrated
framework we propose here has the potential to impact on the way rehabilitation
programs for sensory recovery are carried out, with the promising prospect of
eventually improving their final outcomes.
PMID- 25139762
TI - Contributions of different kainate receptor subunits to the properties of
recombinant homomeric and heteromeric receptors.
AB - The tetrameric kainate receptors can be assembled from a combination of five
different subunit subtypes. While GluK1-3 subunits can form homomeric receptors,
GluK4 and GluK5 require a heteromeric partner to assemble, traffic to the
membrane surface, and produce a functional channel. Previous studies have shown
that incorporation of a GluK4 or GluK5 subunit changes both receptor pharmacology
and channel kinetics. We directly compared the functional characteristics of
recombinant receptors containing either GluK4 or GluK5 in combination with the
GluK1 or GluK2 subunit. In addition, we took advantage of mutations within the
agonist binding sites of GluK1, GluK2, or GluK5 to isolate the response of the
wild-type partner within the heteromeric receptor. Our results suggest that GluK1
and GluK2 differ primarily in their pharmacological properties, but that GluK4
and GluK5 have distinct functional characteristics. In particular, while binding
of agonist to only the GluK5 subunit appears to activate the channel to a non
desensitizing state, binding to GluK4 does produce some desensitization. This
suggests that GluK4 and GluK5 differ fundamentally in their contribution to
receptor desensitization. In addition, mutation of the agonist binding site of
GluK5 results in a heteromeric receptor with a glutamate sensitivity similar to
homomeric GluK1 or GluK2 receptors, but which requires higher agonist
concentrations to produce desensitization. This suggests that onset of
desensitization in heteromeric receptors is determined more by the number of
subunits bound to agonist than by the identity of those subunits. The distinct,
concentration-dependent properties observed with heteromeric receptors in
response to glutamate or kainate are consistent with a model in which either
subunit can activate the channel, but in which occupancy of both subunits within
a dimer is needed to allow desensitization of GluK2/K5 receptors.
PMID- 25139763
TI - High-performing dry powder inhalers of paclitaxel DPPC/DPPG lung surfactant-mimic
multifunctional particles in lung cancer: physicochemical characterization, in
vitro aerosol dispersion, and cellular studies.
AB - Inhalable lung surfactant-based carriers composed of synthetic phospholipids,
dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG),
along with paclitaxel (PTX), were designed and optimized as respirable dry
powders using organic solution co-spray-drying particle engineering design. These
materials can be used to deliver and treat a wide variety of pulmonary diseases
with this current work focusing on lung cancer. In particular, this is the first
time dry powder lung surfactant-based particles have been developed and
characterized for this purpose. Comprehensive physicochemical characterization
was carried out to analyze the particle morphology, surface structure, solid
state transitions, amorphous character, residual water content, and phospholipid
bilayer structure. The particle chemical composition was confirmed using
attenuated total reflectance-Fourier-transform infrared (ATR-FTIR) spectroscopy.
PTX loading was high, as quantified using UV-VIS spectroscopy, and sustained PTX
release was measured over weeks. In vitro cellular characterization on lung
cancer cells demonstrated the enhanced chemotherapeutic cytotoxic activity of
paclitaxel from co-spray-dried DPPC/DPPG (co-SD DPPC/DPPG) lung surfactant-based
carrier particles and the cytotoxicity of the particles via pulmonary cell
viability analysis, fluorescent microscopy imaging, and transepithelial
electrical resistance (TEER) testing at air-interface conditions. In vitro
aerosol performance using a Next Generation ImpactorTM (NGITM) showed measurable
powder deposition on all stages of the NGI and was relatively high on the lower
stages (nanometer aerodynamic size). Aerosol dispersion analysis of these high
performing DPIs showed mass median diameters (MMADs) that ranged from 1.9 to 2.3
MUm with excellent aerosol dispersion performance as exemplified by high values
of emitted dose, fine particle fractions, and respirable fractions.
PMID- 25139764
TI - Photodegradation of moxifloxacin in aqueous and organic solvents: a kinetic
study.
AB - The kinetics of photodegradation of moxifloxacin (MF) in aqueous solution (pH 2.0
12.0), and organic solvents has been studied. MF photodegradation is a specific
acid-base catalyzed reaction and follows first-order kinetics. The apparent first
order rate constants (kobs) for the photodegradation of MF range from 0.69 * 10(
4) (pH 7.5) to 19.50 * 10(-4) min(-1) (pH 12.0), and in organic solvents from
1.24 * 10(-4) (1-butanol) to 2.04 * 10(-4) min(-1) (acetonitrile). The second
order rate constant (k2) for the [H(+)]-catalyzed and [OH(-)]-catalyzed reactions
are 6.61 * 10(-2) and 19.20 * 10(-2) M(-1) min(-1), respectively. This indicates
that the specific base-catalyzed reaction is about three-fold faster than that of
the specific acid-catalyzed reaction probably as a result of the rapid cleavage
of diazabicyclononane side chain in the molecule. The kobs-pH profile for the
degradation reactions is a V-shaped curve indicating specific acid-base
catalysis. The minimum rate of photodegradation at pH 7-8 is due to the presence
of zwitterionic species. There is a linear relation between kobs and the
dielectric constant and an inverse relation between kobs and the viscosity of the
solvent. Some photodegraded products of MF have been identified and pathways
proposed for their formation in acid and alkaline solutions.
PMID- 25139765
TI - Abdominal cocoon as a presenting feature of systemic lupus erythematous. A rare
presentation.
PMID- 25139766
TI - Extracavitary primary effusion lymphoma: clinical, morphological, phenotypic and
cytogenetic characterization using nuclei enrichment technique.
AB - AIMS: Primary effusion lymphoma (PEL) is a rare form of aggressive B-cell
lymphoma, which typically manifests as malignant effusion in the body cavities.
However, extracavitary solid variants are also described. The aim of this study
was to investigate copy number aberrations in two cases of solid PEL at their
first occurrences and relapse by applying a newly developed methodology of tumour
nuclei enrichment. METHODS AND RESULTS: Using histological and genetic
techniques, a novel protocol for tumour nuclei enrichment by flow sorting and
array-comparative genomic hybridization, we characterized two cases of
extracavitary PEL, one of which later relapsed as effusion. Both primary tumours
were positive for HHV8 and EBV, confined to lymph nodes, and aberrantly expressed
CD3, yet displaying clonal immunoglobulin gene rearrangements indicating B-cell
origin. Cytogenetic characterization of primary tumours revealed modest number of
aberrations, partially overlapping with previously reported affected loci. The
effusional relapse in case 1 was cytogenetically related to the primary tumour
but showed dramatic increase of chromosomal instability. CONCLUSIONS: We for the
first time demonstrate a cytogenetic relationship between solid and effusional
presentations of PEL. Moreover, we provide an indirect evidence of multiple
malignant clones, which gave rise to clonally-related, yet karyotypically
different relapsing lymphoma manifestations.
PMID- 25139767
TI - The clinical interpretation of peritoneal equilibration test.
PMID- 25139768
TI - Responses of five Mediterranean halophytes to seasonal changes in environmental
conditions.
AB - In their natural habitats, different mechanisms may contribute to the tolerance
of halophytes to high soil salinity and other abiotic stresses, but their
relative contribution and ecological relevance, for a given species, remain
largely unknown. We studied the responses to changing environmental conditions of
five halophytes (Sarcocornia fruticosa, Inula crithmoides, Plantago crassifolia,
Juncus maritimus and J. acutus) in a Mediterranean salt marsh, from summer 2009
to autumn 2010. A principal component analysis was used to correlate soil and
climatic data with changes in the plants' contents of chemical markers associated
with stress responses: ions, osmolytes, malondialdehyde (MDA, a marker of
oxidative stress) and antioxidant systems. Stress tolerance in S. fruticosa, I.
crithmoides and P. crassifolia (all succulent dicots) seemed to depend mostly on
the transport of ions to aerial parts and the biosynthesis of specific osmolytes,
whereas both Juncus species (monocots) were able to avoid accumulation of toxic
ions, maintaining relatively high K(+)/Na(+) ratios. For the most salt-tolerant
taxa (S. fruticosa and I. crithmoides), seasonal variations of Na(+), Cl(-), K(+)
and glycine betaine, their major osmolyte, did not correlate with environmental
parameters associated with salt or water stress, suggesting that their tolerance
mechanisms are constitutive and relatively independent of external conditions,
although they could be mediated by changes in the subcellular
compartmentalization of ions and compatible osmolytes. Proline levels were too
low in all the species to possibly have any effect on osmotic adjustment. However
except for P. crassifolia-proline may play a role in stress tolerance based on
its 'osmoprotectant' functions. No correlation was observed between the degree of
environmental stress and the levels of MDA or enzymatic and non-enzymatic
antioxidants, indicating that the investigated halophytes are not subjected to
oxidative stress under natural conditions and do not, therefore, need to activate
antioxidant defence mechanisms.
PMID- 25139769
TI - Effect of saline water on seed germination and early seedling growth of the
halophyte quinoa.
AB - Salinization is increasing on a global scale, decreasing average yields for most
major crop plants. Investigations into salt resistance have, unfortunately,
mainly been focused on conventional crops, with few studies screening the
potential of available halophytes as new crops. This study has been carried out
to investigate the mechanisms used by quinoa, a facultative halophytic species,
in order to cope with high salt levels at various stages of its development.
Quinoa is regarded as one of the crops that might sustain food security in this
century, grown primarily for its edible seeds with their high protein content and
unique amino acid composition. Although the species has been described as a
facultative halophyte, and its tolerance to salt stress has been investigated,
its physiological and molecular responses to seawater (SW) and other salts have
not been studied. We evaluated the effects of SW and different salts on seed
germination, seedling emergence and the antioxidative pathway of quinoa. Seeds
were germinated in Petri dishes and seedlings grown in pots with SW solutions
(25, 50, 75 and 100 %) and NaCl, CaCl2, KCl and MgCl2 individually, at the
concentrations in which they are present in SW. Our results demonstrated that all
salts, at lower concentrations, increased the germination rate but not the
germination percentages, compared with control (pure water). Conversely,
seedlings were differently affected by treatments in respect to salt type and
concentration. Growth parameters affected were root and shoot length, root
morphology, fresh and dry weight, and water content. An efficient antioxidant
mechanism was present in quinoa, activated by salts during germination and early
seedling growth, as shown by the activities of antioxidant enzymes. Total
antioxidant capacity was always higher under salt stress than in water. Moreover,
osmotic and ionic stress factors had different degrees of influence on
germination and development.
PMID- 25139770
TI - Control of main risk factors after ischaemic stroke across Europe: data from the
stroke-specific module of the EUROASPIRE III survey.
AB - BACKGROUND: Previous cross-sectional surveys in different European countries
within the EUROASPIRE programme demonstrated a high prevalence of modifiable risk
factors, unhealthy lifestyles and inadequate drug treatment in coronary heart
disease patients. Comparable data for ischaemic stroke patients is lacking.
METHODS: A stroke-specific study module was added to the EUROASPIRE III core
survey. This cross-sectional multicentre survey included consecutive patients
with first-ever ischaemic stroke from four European countries. Data were obtained
from medical records, patient interviews and patient examinations within 6-36
months after the stroke event. Control of modifiable risk factors after stroke
was evaluated against contemporary European guidelines. RESULTS: A total of 881
patients was recruited. Median age was 66 years, 37.5% were female; average time
from the stroke event to interview was 550 days. At the time of the interview,
17.6% of stroke patients smoked cigarettes, 35.5% had a body mass index >=30
kg/m(2), 62.4% showed elevated blood pressure and 75.7% exhibited elevated LDL
cholesterol levels. Antiplatelet drugs or oral anticoagulants were used by 87.2%,
antihypertensive medication by 84.4% and statins by 56.8% of stroke patients.
Among patients using antihypertensive drugs and lipid-lowering medication at the
time of the interview, 34.3% and 34.4%, respectively, achieved target blood
pressure and total cholesterol values according to current European guidelines.
CONCLUSION: The EUROASPIRE III stroke-specific module shows that secondary
prevention and risk factor control in patients after ischaemic stroke need to be
improved in four European centres at the time of the study since about half of
patients are not achieving risk factor targets defined in European guidelines.
PMID- 25139771
TI - New myocardial infarction definition affects incidence, mortality,
hospitalization rates and prognosis.
AB - AIMS: To analyse differences in myocardial infarction incidence, mortality and
hospitalization rates, 28-day case-fatality and two-year prognosis using two
myocardial infarction case definitions: the classical World Health Organization
definition (1994) and the European Society of Cardiology/American College of
Cardiology definition (2000), which added cardiac troponin as a diagnostic
biomarker. DESIGN: Population-based cohort of 4170 consecutive myocardial
infarction patients aged 35-74 years from Girona (Spain) recruited between 2002
and 2009. METHODS: Incidence, mortality rates standardized to the European
population and 28-day case-fatality were calculated. To estimate the association
between case definition and prognosis, Cox models were fitted. RESULTS: Use of
the 2000 European Society of Cardiology/American College of Cardiology definition
significantly increased myocardial infarction incidence per 100,000 population
(238.3 vs. 274.5 in men and 54.1 vs. 69.7 in women). Applying this definition
decreased the 28-day case-fatality rate from 26.9% to 23.4% in men, and from
31.0% to 24.1% in women. In the acute phase, patients diagnosed only by increased
troponins were significantly less treated with thrombolysis (34.4% vs. 2.0%),
angiotensin-converting enzyme inhibitors (71.7% vs. 65.0%) and percutaneous
coronary intervention (41.1% vs. 31.7%). Case-fatality at 28 days was
significantly better in cases diagnosed only by troponin increase (0.2 % vs.
9.7%), but two-year cardiovascular mortality was higher (7.5% vs. 3.7%).
CONCLUSIONS: Inclusion of cardiac troponins in myocardial infarction diagnosis
increased annual incidence and decreased case-fatality. Diagnosis based only on
increased troponins was associated with worse outcome. This group of patients at
high risk of death should receive aggressive secondary prevention therapy.
PMID- 25139772
TI - Predictors of cardiovascular events in patients with systemic lupus erythematosus
(SLE): a systematic review and meta-analysis.
AB - BACKGROUND: Cardiovascular disease represents an important cause of morbidity and
mortality in patients with a diagnosis of systemic lupus erythematosus (SLE), due
to a complex interplay between traditional risk factors and disregulation of
autoimmunity but uncertainty is still present about the most important predictors
of cardiovascular events. OBJECTIVES: The aim of our work was to perform a
collaborative systematic review on the main predictors of cardiovascular events
in SLE patients. METHODS: PubMed and Cochrane were systematically searched for
eligible studies on SLE and cardiovascular events between January 2008 and
December 2012. Study features, patient characteristics and incidence of stent
thrombosis were abstracted and pooled, when appropriate, with random-effect
methods (point estimate - 95% confidence intervals) and consistency of predictors
was formally appraised. RESULTS: A total of 17,187 patients was included; of
those, 93.1% were female and the median age was 39 years. After a median follow
up period of 8 years, cardiovascular events presented in 25.4%, including acute
myocardial infarction (4.1%) and stroke (7.3%). The most important predictors may
be divided into traditional risk factors, such as male gender (OR 6.2, CI 95%
1.49-25), hyperlipidaemia (OR 3.9, CI 95% 1.57-9.71), familiar history of cardiac
disease (OR 3.6, CI 95% 1.15-11.32) and hypertension (OR 3.5, CI 95% 1.65-7.54),
and SLE-related features, such as the presence of auto-antibodies (OR 5.8 and
5.0, CI 95% 3.28-7.78) and neurological disorders (OR 5.2, CI 95% 2.0-13.9). A
low correlation was shown for the importance of organ damage and SLE activity
(respectively OR 1.4, CI 95% 1.09-4.44 and OR 1.2, CI 95% 1.2-1.2), as well as
for age at diagnosis (OR 1.1, CI 95% 1.07-1.17). CONCLUSIONS: Cardiovascular
events in SLE patients are caused by a multifactorial mechanism, including both
traditional and disease-specific risk factors. A global valuation with an
individual risk stratification based on both these features is important to
correctly manage these patients in order to reduce negative outcomes.
PMID- 25139773
TI - Molecular pathways regulating the formation of brown-like adipocytes in white
adipose tissue.
AB - Adipose tissue is functionally composed of brown adipose tissue and white adipose
tissue. The unique thermogenic capacity of brown adipose tissue results from
expression of uncoupling protein 1 in the mitochondrial inner membrane. On the
basis of recent findings that adult humans have functionally active brown adipose
tissue, it is now recognized as playing a much more important role in human
metabolism than was previously thought. More importantly, brown-like adipocytes
can be recruited in white adipose tissue upon environmental stimulation and
pharmacologic treatment, and this change is associated with increased energy
expenditure, contributing to a lean and healthy phenotype. Thus, the promotion of
brown-like adipocyte development in white adipose tissue offers novel
possibilities for the development of therapeutic strategies to combat obesity and
related metabolic diseases. In this review, we summarize recent advances in
understanding the molecular mechanisms involved in the recruitment of brown-like
adipocyte in white adipose tissue.
PMID- 25139774
TI - [Scrotal space-occupying lesions].
AB - Palpable scrotal masses are common scenarios in any clinical practice. These
tumors can be painful or painless, can be intratesticular or extratesticular and
be cystic or solid. The distinction between benign and malignant tumors is of
utmost importance to enable an adequate and differentiated therapy of patients.
In clinical diagnostics besides the medical history, examination of the
inguinoscrotal region, laboratory diagnostics and ultrasound examination of the
inguinoscrotal area play a decisive role. During the last few years the increased
use of contrast-enhanced ultrasound has helped clinicians in differentiating
scrotal tumors. Malignant tumors are of particular importance because this entity
is the most frequent malignant disease among younger men and according to the
Robert Koch Institute there are approximately 3900 new patients in Germany each
year (Robert Koch Institute, Krebs in Deutschland 2007/2008 and 2012).
PMID- 25139775
TI - Prediction of coronary plaque location on arteries having myocardial bridge,
using finite element models.
AB - This study was performed to evaluate the influences of the myocardial bridges on
the plaque initializations and progression in the coronary arteries. The wall
structure is changed due to the plaque presence, which could be the reason for
multiple heart malfunctions. Using simplified parametric finite element model (FE
model) of the coronary artery having myocardial bridge and analyzing different
mechanical parameters from blood circulation through the artery (wall shear
stress, oscillatory shear index, residence time), we investigated the prediction
of "the best" position for plaque progression. We chose six patients from the
angiography records and used data from DICOM images to generate FE models with
our software tools for FE preprocessing, solving and post-processing. We found a
good correlation between real positions of the plaque and the ones that we
predicted to develop at the proximal part of the myocardial bridges with wall
shear stress, oscillatory shear index and residence time. This computer model
could be additional predictive tool for everyday clinical examination of the
patient with myocardial bridge.
PMID- 25139776
TI - Molecular diagnosis of infectious diarrhea: focus on enteric protozoa.
AB - Robust detection of enteric protozoa is a critical step toward determining the
etiology of diarrhea. Widespread use of conventional microscopy, culturing and
antigen detection in both industrial and developing countries is limited by
relatively low sensitivity and specificity. Refinements of these conventional
approaches that reduce turnaround time and instrumentation have yielded strong
alternatives for clinical and research use. However, advances in molecular
diagnostics for protozoal, bacterial, viral and helminth infections offer
significant advantages in studies seeking to understand pathogenesis,
transmission and long-term consequences of infectious diarrhea. Quantitation of
enteropathogen burden and highly multiplexed platforms for molecular detection
dramatically improve predictive power in emerging models of diarrheal etiology,
while eliminating the expense of multiple tests.
PMID- 25139777
TI - Out-of-office blood pressure improves risk stratification in normotension and
prehypertension people.
AB - This review addresses to what extent out-of-office blood pressure, the ambulatory
blood pressure monitoring and the self-measured home blood pressure, refines
conventional blood pressure-based risk stratification across increasing blood
pressure categories, in particular individuals assumed to be associated with no
or only mildly increased risk. Compared with sustained normotension, individuals
with prehypertension as well as masked hypertension tend to be developed to true
hypertension. Ambulatory blood pressure measurement refines risk stratification
among prehypertensive people. Home blood pressure is more useful for the
prediction of cerebrovascular diseases than conventional blood pressure, by
replacing information from conventional to home blood pressure in risk
stratification system. Furthermore, the two participant-level meta-analyses
demonstrated that the out-of-office blood pressure substantially refines risk
stratification in normotension and prehypertension, particularly among
participants with masked hypertension. Properly organized randomized clinical
trials are required to demonstrate that identification and treatment of masked
hypertension, compared with the current standard care based on conventional
pressure, lead to the reduction of cardiovascular diseases in population and are
cost-effective.
PMID- 25139778
TI - Treatment of hypertension and metabolic syndrome: lowering blood pressure is not
enough for organ protection, new approach-arterial destiffening.
AB - Cardiovascular risk factors (CVRFs) have been shown to induce end organ damage.
Until now, the main approach to reduce CVRF-induced end organ damage was by
normalization of CVRFs; this approach was found effective to reduce damage and
cardiovascular (CV) events. However, a residual risk always remained even when
CVRFs were optimally balanced. An additional risk factor which has an immense
effect on the progression of end organ damage is aging. Aging is accompanied by
gradual stiffening of the arteries which finally leads to CV events. Until
recently, the process of arterial aging was considered as unmodifiable, but this
has changed. Arterial stiffening caused by the aging process is similar to the
changes seen as a result of CVRF-induced arterial damage. Actually, the presence
of CVRFs causes faster arterial stiffening, and the extent of damage is
proportional to the severity of the CVRF, the length of its existence, the
patient's genetic factors, etc. Conventional treatments of osteoporosis and of
hormonal decline at menopause are potential additional approaches to positively
affect progression of arterial stiffening. The new approach to further decrease
progression of arteriosclerosis, thus preventing events, is the prevention of age
associated arterial structural changes. This approach should further decrease age
associated arterial stiffening. A totally new promising approach is to study the
possibility of affecting collagen, elastin, and other components of connective
tissue that participate in the process of arterial stiffening. Reduction of pulse
pressure by intervention in arterial stiffening process by novel methods as
breaking collagen cross-links or preventing their formation is an example of
future directions in treatment. This field is of enormous potential that might be
revolutionary in inducing further significant reduction of cardiovascular events.
PMID- 25139779
TI - Ambulatory blood pressure phenotypes and the risk for hypertension.
AB - Ambulatory blood pressure (BP) monitoring provides valuable information on a
person's BP phenotype. Abnormal ambulatory BP phenotypes include white-coat
hypertension, masked hypertension, nocturnal nondipping, nocturnal hypertension,
and high BP variability. Compared to people with sustained normotension (normal
BP in the clinic and on ambulatory BP monitoring), the limited research available
suggests that the risk of developing sustained hypertension (abnormal BP in the
clinic and on ambulatory BP monitoring) over 5 to 10 years is approximately two
to three times greater for people with white-coat or masked hypertension. More
limited data suggest that nondipping might predate hypertension, and no studies,
to our knowledge, have examined whether nocturnal hypertension or high ambulatory
BP variability predict hypertension. Ambulatory BP monitoring may be useful in
identifying people at increased risk of developing sustained hypertension, but
the clinical utility for such use would need to be further examined.
PMID- 25139780
TI - Obstructive sleep apnea and hypertension: a critical review.
AB - Obstructive sleep apnea (OSA) is a prevalent sleep disorder which is
characterized by recurrent upper closure with oxygen desaturation and sleep
disruption. OSA increases the risk of vascular disorders in the form of stroke,
myocardial infarction, congestive heart failure, and hypertension. The mechanisms
underlying the vascular disorders are several and include intermittent hypoxia
with release of cytokines, angiogenic inhibitors, free radicals, and adhesion
molecules. During apneas, arterial blood pressure gradually rises and surges
abruptly after the termination of apnea. Two thirds of patients with OSA will
ultimately have diurnal hypertension. This review discusses the literature
supporting the significant role of OSA in hypertension and the effect of OSA
treatment on blood pressure.
PMID- 25139781
TI - Psychosocial risk factors for hypertension: an update of the literature.
AB - A growing body of research demonstrates that psychosocial factors play an
important role in the development of hypertension. Previous reviews have
identified several key factors (i.e., occupational stress) that contribute to the
onset of hypertension; however, they are now outdated. In this review, we provide
an updated synthesis of the literature from 2010 to April 2014. We identified 21
articles for inclusion in the review, of which there were six categories of
psychosocial stressors: occupational stress, personality, mental health, housing
instability, social support/isolation, and sleep quality. Sixteen of the studies
reported an association between the psychosocial stressor and blood pressure.
While several findings were consistent with previous literature, new findings
regarding mediating and moderating factors underlying the psychosocial
hypertension association help to untangle inconsistencies reported in the
literature. Moreover, sleep quality is a novel additional factor that should
undergo further exploration. Areas for future research based on these findings
are discussed.
PMID- 25139782
TI - Resistant or refractory hypertension: are they different?
AB - Resistant hypertension (RHTN) consists in a condition where blood pressure (BP)
levels remain uncontrolled despite the use of at least three drugs or if the
control happens with four or more drugs. Throughout the last 50 years, it has
been increasingly studied, and its phenotypes have been identified. The term
refractory hypertension has been used concurrently with RHTN all those years, but
in the last decade, it has been applied to the most afflicted part of RHTN-
defined as the uncontrolled RHTN or as the uncontrolled RHTN who needs five or
more drugs. Differences between those two phenotypes are being recently
identified, especially classifying refractory subjects as having more: (1)
cardiovascular risk, (2) target organ damage, (3) African-descending race, (4)
coronary heart disease and myocardial ischemia, (5) aldosterone excess, (6)
deregulation of adipokines, and (7) possible sympathetic hyperactivation. We
review the most important studies in both resistant and refractory hypertension
to gather the up-to-date data regarding the characteristics of these two high
risk groups of patients.
PMID- 25139783
TI - Occupational health nursing in hungary.
AB - This article is the first about occupational health nursing in Hungary. The
authors describe the Hungarian health care and occupational health care systems,
including nursing education and professional organizations for occupational
health nurses. The Fundamental Law of Hungary guarantees the right of every
employee to healthy and safe working conditions, daily and weekly rest times and
annual paid leave, and physical and mental health. Hungary promotes the exercise
of these rights by managing industrial safety and health care, providing access
to healthy food, supporting sports and regular physical exercise, and ensuring
environmental protection. According to the law, the responsibility for regulation
of the occupational health service lies with the Ministry of Human Resources.
Safety regulations are under the aegis of the Ministry of National Economy.
PMID- 25139784
TI - Policy perspectives on occupational stress.
AB - Occupational stress is a major physical and mental hazard for many workers and
has been found to contribute to cardiovascular disease, musculoskeletal
disorders, mood disturbances, workplace injuries, and mental health problems.
Health care utilization related to these physical and mental health problems
costs employers billions of dollars annually. To combat this problem, employers
should adopt a preventive approach and institute organizational and
administrative changes that require the participation of both management and
workers. This article reviews policies that could impact the quality of work life
and influence organizational changes needed to achieve occupational health and
safety. Occupational health nurses play a vital role in designing and
implementing policies to improve work environments and reduce occupational
stress.
PMID- 25139785
TI - Health-related quality of life and functional outcomes from a randomized
withdrawal study of long-term lisdexamfetamine dimesylate treatment in children
and adolescents with attention-deficit/hyperactivity disorder.
AB - BACKGROUND: The stimulant prodrug lisdexamfetamine dimesylate (LDX) is an
effective and generally well tolerated treatment for the symptoms of attention
deficit/hyperactivity disorder (ADHD). Positive impacts of LDX on health-related
quality of life and functional impairment have previously been demonstrated in a
7-week, randomized, double-blind, placebo-controlled, phase III study in children
and adolescents in Europe. Maintenance of these broad benefits, as well as
symptomatic control, is a key goal of long-term management of ADHD. OBJECTIVE:
Secondary objectives of this multinational study in children and adolescents with
ADHD were to assess the long-term maintenance of effectiveness of LDX in
improving health-related quality of life and reducing functional impairment, as
gauged using the Child Health and Illness Profile-Child Edition: Parent Report
Form (CHIP-CE: PRF) and the Weiss Functional Impairment Rating Scale-Parent
Report (WFIRS-P), respectively. METHODS: Patients aged 6-17 years with diagnosed
ADHD and a baseline ADHD Rating Scale IV total score of at least 28 were enrolled
from the previous European study and from US sites. Patients who completed an
open-label LDX treatment period of at least 26 weeks were randomized (1:1) to
continue on their optimized dose of LDX or to switch to placebo for a 6-week,
double-blind, withdrawal period. Parents completed CHIP-CE: PRF and WFIRS-P
questionnaires at weeks 0, 8 and 26 of the open-label period and at weeks 0 and 6
of the randomized-withdrawal period, or at early termination. The endpoint of
each period was defined as the last visit with valid data. Effect sizes were the
difference (LDX minus placebo) in least-squares (LS)-mean change from baseline to
endpoint divided by root-mean-square error. P values were nominal and not
adjusted for multiple comparisons. RESULTS: The open-label and randomized full
analysis sets comprised 262 and 153 (LDX n = 76; placebo n = 77) patients,
respectively. Mean pretreatment CHIP-CE: PRF T-scores were more than one standard
deviation below the normative mean in four of the five domains, and there was
significant improvement across all domains from baseline to endpoint of the open
label period. In the randomized-withdrawal period, LS-mean CHIP-CE: PRF T-scores
deteriorated in all domains in the placebo group, but not in the LDX group.
Compared with placebo, the effect of LDX was significant in the Risk Avoidance
(effect size 0.829; p < 0.001), Achievement (0.696; p < 0.001) and Satisfaction
(0.636; p < 0.001) domains. Mean pretreatment WFIRS-P scores were lowest in the
Family domain and the Learning and School domain. WFIRS-P total score and scores
in all domains improved significantly from baseline to endpoint of the open-label
period. In the randomized-withdrawal period, LS-mean scores deteriorated in the
placebo group but not in the LDX group. Compared with placebo, the effect of LDX
was significant in the Family, Learning and School, and Risky Activities domains
and in total (effect size 0.908; p < 0.001). CONCLUSIONS: Using parent-rated
instruments, long-term maintenance of the beneficial effect of LDX in multiple
domains of health-related quality of life and functional impairment was
demonstrated by comparison of treatment continuation and withdrawal under
randomized, double-blind, placebo-controlled conditions.
PMID- 25139786
TI - Effect of music in endoscopy procedures: systematic review and meta-analysis of
randomized controlled trials.
AB - OBJECTIVE: Endoscopies are common clinical examinations that are somewhat painful
and even cause fear and anxiety for patients. We performed this systematic review
and meta-analysis of randomized controlled trials to determine the effect of
music on patients undergoing various endoscopic procedures. METHODS: We searched
the Cochrane Library, Issue 6, 2013, PubMed, and EMBASE databases up to July
2013. Randomized controlled trials comparing endoscopies, with and without the
use of music, were included. Two authors independently abstracted data and
assessed risk of bias. Subgroup analyses were performed to examine the impact of
music on different types of endoscopic procedures. RESULTS: Twenty-one randomized
controlled trials involving 2,134 patients were included. The overall effect of
music on patients undergoing a variety of endoscopic procedures significantly
improved pain score (weighted mean difference [WMD] = -1.53, 95% confidence
interval [CI] [-2.53, -0.53]), anxiety (WMD = -6.04, 95% CI [-9.61, -2.48]),
heart rate (P = 0.01), arterial pressure (P < 0.05), and satisfaction score (SMD
= 1.83, 95% CI [0.76, 2.91]). Duration of the procedure (P = 0.29), except for
gastrointestinal endoscopy (P = 0.03), and sedative or analgesic medication dose
(P = 0.23, P = 0.12, respectively) were not significantly decreased in the music
group, compared with the control group. Furthermore, music had little effect for
patients undergoing colposcopy and bronchoscopy in the subanalysis. CONCLUSION:
Our meta-analysis suggested that music may offer benefits for patients undergoing
endoscopy, except in colposcopy and bronchoscopy.
PMID- 25139788
TI - PARP inhibition and the radiosensitizing effects of the PARP inhibitor ABT-888 in
in vitro hepatocellular carcinoma models.
AB - BACKGROUND: Hepatocellular carcinoma is the third cause of cancer related death
for which new treatment strategies are needed. Targeting DNA repair pathways to
sensitize tumor cells to chemo- or radiotherapy is under investigation for the
treatment of several cancers with poly(ADP-ribose) polymerase (PARP) inhibitors
showing great potential. The aim of this preclinical study was to evaluate the
expression of PARP and PARG genes in a panel of liver cancer cell lines and
primary human hepatocytes, their DNA repair capacity and assess the impact on
cell survival of PARP inhibitors alone and in combination with radiotherapy.
METHODS: Quantitative PCR was used to measure PARP-1, -2, -3 and PARG mRNA levels
and western blotting for PARP-1 protein expression and ADP-ribose polymer
formation after exposure of cells to doxorubicin, a topoisomerase II poison. DNA
repair capacity was assessed using an in vitro DNA lesion excision/synthesis
assay and the effects on cell killing of the PARP inhibitor ABT-888 alone and in
combination with ionizing radiation using clonogenic survival. RESULTS: Although
a wide range in expression of the PARPs and PARG was found correlations between
PARP-1 and PARP-2 mRNA levels and PARP-1 mRNA and protein levels were noted.
However these expression profiles were not predictive of PARP activity in the
different cell lines that also showed variability in excision/synthesis repair
capacity. 4 of the 7 lines were sensitive to ABT-888 alone and the two lines
tested showed enhanced radiosensitivity in the presence of ABT-888. CONCLUSIONS:
PARP inhibitors combined with radiotherapy show potential as a therapeutic option
for hepatocellular carcinoma.
PMID- 25139789
TI - Cardiac autonomic dysfunction in patients with head-up tilt test-induced
vasovagal syncope.
AB - BACKGROUND: Vasovagal syncope (VVS) is the result of an autonomic reflex that has
a final effect of reducing sympathetic drive and increasing vagal activity.
However, whether syncopal symptoms are associated with pathological cardiac
autonomic modulation is not fully known. We tested the hypothesis that cardiac
autonomic function is impaired in patients with VVS. METHODS: Eighty-four
consecutive patients (59 males; 48.8 +/- 20.9 years) with recurrent unexplained
syncope were enrolled. The head-up tilt test (HUTT) was positive in 38 patients
and negative in 46 patients. Cardiac autonomic function was assessed by
baroreflex sensitivity (BRS), heart rate variability, plasma concentrations of
norepinephrine, and (123) I-metaiodobenzylguanidine (MIBG) scintigraphy. RESULTS:
BRS indices were significantly lower in the HUTT-positive group than in the HUTT
negative group (6.1 +/- 5.5 mm Hg/s vs 9.8 +/- 7.6 mm Hg/s, P = 0.02). With
regard to cardiac (123) I-MIBG scintigraphy, the mean heart-to-mediastinum ratio
at the delayed phase tended to be lower in HUTT-positive than in HUTT-negative
individuals, but this difference was not significant (2.75 +/- 0.55 vs 3.02 +/-
0.49, P = 0.08).The percent washout rate of (123) I-MIBG was significantly higher
in the positive group compared with the negative group (40.7 +/- 13.1% vs 31.5 +/
13.3%, P = 0.02). Multivariate logistic analysis revealed that the appearance of
HUTT-induced VVS was predicted independently by a high percent washout rate of
(123) I-MIBG (odds ratio, 0.954; 95% confidence interval, 0.903-0.998; P =
0.048). CONCLUSIONS: Our results suggest that pathological autonomic cardiac
modulation may play a role in the appearance of syncope in VVS patients.
PMID- 25139790
TI - Editorial overview: In vivo chemistry: Pushing the envelope.
PMID- 25139791
TI - Age patterns of Kaposi's sarcoma incidence in a cohort of HIV-infected men.
AB - The life expectancy for HIV-positive individuals has improved over time due to
increasing access to highly active antiretroviral therapy (HAART). Yet, as the
HIV-positive population ages, their risk of developing cancers also increases.
Studies of Kaposi's sarcoma (KS) among elderly HIV-infected persons are quite
limited. We examined the age patterns of KS incidence and an association between
age and KS risk in a US cohort of 3458 HIV-infected men, the Multicenter AIDS
Cohort Study (MACS). Poisson distribution was used to calculate incidence rates
and respective 95% confidence intervals (95% CIs). Cox proportional hazards
regression was performed to examine the association between age and KS risk.
There were 534 incident KS cases with a total follow-up time of 25,134 person
years. The overall KS incidence rate was 2.13 per 100 person-years (95% CI: 1.95
2.32) (Non-HAART users-ever: 5.57 per 100 person-years [95% CI: 5.09-6.10]; HAART
users-ever: 0.39 per 100 person-years [95% CI: 0.31-0.51]). Overall, KS frequency
and incidence declined with age, even in the oldest age group (p(trend) <
0.0001). However, among non-HAART users-ever, the oldest age group had the
highest incidence rate ratio compared to younger individuals [15.01, 95% CI: 6.12
44.22]). While the incidence of KS decreased with age, older HIV-infected persons
who do not receive HAART are still at increased risk of KS. As KS remains an
important malignancy among HIV-infected persons, earlier HIV diagnoses and HAART
initiation, particularly in older HIV-infected persons is warranted.
PMID- 25139792
TI - Assessment of a fluorescent antibody test for the detection of antibodies against
epizootic bovine abortion.
AB - The current study was directed at developing and validating an indirect
fluorescent antibody test (IFAT) capable of detecting antibodies specific for the
agent of epizootic bovine abortion (aoEBA). Sensitivity and specificity was
determined by comparing antibody titers from 114 fetuses infected with aoEBA with
68 fetuses diagnosed with alternate infectious etiologies. Data established
specificity at 100% and sensitivity at 94.7% when cutoff criteria for a positive
test were assigned at a titer of >=1,000. Potential cross-reactivity was noted in
samples from 3 fetuses with antibody titers of 10 or100; all were infected with
Gram-positive organisms. The remaining 65 fetuses infected with microbes other
than aoEBA, and an additional 12 negative reference sera, did not have detectable
titers. The IFAT-based serology assay is rapid, reproducible, and unaffected by
fluid color or opacity. Total fetal immunoglobulin (Ig)G was also evaluated as an
aid for diagnosing EBA. Significantly higher concentrations of IgG were
identified in fetuses infected with aoEBA as compared to those with alternate
infectious etiologies. The presence of IgG is a sensitive indicator of EBA and
increases the specificity of FAT-based serologic diagnosis when titers are 10 or
100. Taken together, serology and IgG analyses suggest that the incidence of EBA
may be underestimated.
PMID- 25139793
TI - Variable-number tandem repeats genotyping used to aid and inform management
strategies for a bovine Johne's disease incursion in tropical and subtropical
Australia.
AB - The application of variable-number tandem repeats (VNTR) genotyping of
Mycobacterium avium subsp. paratuberculosis isolates to assist in investigating
incidents of bovine Johne's disease in a low-prevalence region of Australia is
described in the current study. Isolates from a response to detection of bovine
Johne's disease in Queensland were compared with strains from national and
international sources. The tandem application of mycobacterial interspersed
repetitive unit (MIRU) and multilocus short sequence repeats (MLSSR) genotyping
identified 2 strains, 1 that infected cattle on multiple properties with trace
forward histories from a common infected property, and 1 genotypically different
strain recovered from a single property. The former strain showed an identical
genotype to an isolate from India. Neither strain showed a genotypic link to
regions of Australia with a higher prevalence of the disease. Genotyping has
indicated incursions from 2 independent sources. This intelligence has informed
investigations into potential routes of entry and the soundness of ongoing
control measures, and supported strategy and policy decisions regarding
management of Mycobacterium avium subsp. paratuberculosis incursions for
Queensland.
PMID- 25139795
TI - The welfare impact of parallel imports: a structural approach applied to the
German market for oral anti-diabetics.
AB - We investigate the welfare impact of parallel imports using a large panel dataset
containing monthly information on sales, ex-factory prices, and further product
characteristics for all 649 anti-diabetic drugs sold in Germany between 2004 and
2010. We estimate a two-stage nested logit model of demand, and on the basis of
an oligopolistic model of multi-product firms, we then recover the marginal costs
and markups. We finally evaluate the effect of the parallel imports' policy by
calculating a counterfactual scenario without parallel trade. According to our
estimates, parallel imports reduce the prices for patented drugs by 11% and do
not have a significant effect on prices for generic drugs. This amounts to an
increase in the demand-side surplus by ?19 million per year (or ?130 million in
total), which is relatively small compared with the average annual market size of
around ?227 million based on ex-factory prices. The variable profits for the
manufacturers of original drugs from the German market are reduced by ?18 million
(or 37%) per year when parallel trade is allowed, yet only one third of this
difference is appropriated by the importers.
PMID- 25139796
TI - Use of lyophilised and powdered Gentiana lutea root in fresh beef patties stored
under different atmospheres.
AB - BACKGROUND: Gentiana lutea root is a medicinal herb that contains many active
compounds which contribute to physiological effects, and it has recently
attracted much attention as a natural source of antioxidants. The aim of this
study was to evaluate the effects on the colour, pH, microbial activities,
sensory quality and resistance to lipid oxidation (through the thiobarbituric
acid method) during storage of beef patties containing different concentrations
of G. lutea. Fresh beef patties were formulated with 0-5 g kg(-1) of G. lutea and
0 or 0.5 g kg(-1) of ascorbic acid and packed in two different atmospheres,
Modified Atmosphere 1 (MAP1) and Modified Atmosphere 2 (MAP2), and stored at 4 +/
1 degrees C for 10 days. MAP1 contained 20:80 (v/v) O2:CO2 and MAP2 contained
80:20 (v/v) O2:CO2. RESULTS: G. lutea extracts possessed antioxidant activity
measured by the ferric reducing antioxidant power and the oxygen radical
absorbance capacity assays. Beef patties containing 2 g kg(-1) of lyophilised G.
lutea were stable towards lipid oxidation in both atmospheres (P < 0.05). Beef
patties containing a combination of 2 g kg(-1) G. lutea and 0.5 g kg(-1) ascorbic
acid showed significantly reduced changes in colour and in lipid oxidation (P <
0.05). CONCLUSION: The results from this study demonstrate the potential of G.
lutea as a food ingredient in the design of healthier meat commodities.
PMID- 25139797
TI - Metabolomic analysis of extreme freezing tolerance in Siberian spruce (Picea
obovata).
AB - Siberian spruce (Picea obovata) is one of several boreal conifer species that can
survive at extremely low temperatures (ELTs). When fully acclimated, its tissues
can survive immersion in liquid nitrogen. Relatively little is known about the
biochemical and biophysical strategies of ELT survival. We profiled needle
metabolites using gas chromatography coupled with mass spectrometry (GC-MS) to
explore the metabolic changes that occur during cold acclimation caused by
natural temperature fluctuations. In total, 223 metabolites accumulated and 52
were depleted in fully acclimated needles compared with pre-acclimation needles.
The metabolite profiles were found to develop in four distinct phases, which are
referred to as pre-acclimation, early acclimation, late acclimation and fully
acclimated. Metabolite changes associated with carbohydrate and lipid metabolism
were observed, including changes associated with increased raffinose family
oligosaccharide synthesis and accumulation, accumulation of sugar acids and sugar
alcohols, desaturation of fatty acids, and accumulation of digalactosylglycerol.
We also observed the accumulation of protein and nonprotein amino acids and
polyamines that may act as compatible solutes or cryoprotectants. These results
provide new insight into the mechanisms of freezing tolerance development at the
metabolite level and highlight their importance in rapid acclimation to ELT in P.
obovata.
PMID- 25139798
TI - Reduced gene expression levels of Munc13-1 and additional components of the
presynaptic exocytosis machinery upon conditional targeting of Vglut2 in the
adolescent mouse.
AB - Presynaptic proteins orchestrate an intricate interplay of dynamic interactions
in order to regulate quantal exocytosis of transmitter-filled vesicles, and their
dysregulation might cause neurological and neuropsychiatric dysfunction. Mice
carrying a spatiotemporal restriction in the expression of the Vesicular
glutamate transporter 2 (Vglut2; aka Slc17a6) in the cortex, amygdala and
hippocampal subiculum from the third postnatal week show a strong anxiolytic
phenotype and certain behavioral correlates of schizophrenia. To further
understand the molecular consequences of this targeted deletion of Vglut2, we
performed an unbiased microarray analysis comparing gene expression levels in the
subiculum of these conditional Vglut2 knockout mice (Vglut2f/f;CamKII cKO) to
those in control littermates. Expression of Unc13C (Munc13-3), a member of the
Unc/Munc family, previously shown to be important for glutamatergic transmission,
was identified to be significantly down-regulated. Subsequent analysis by
quantitative RT-PCR revealed a 50% down-regulation of Munc 13-1, the gene
encoding the Unc/Munc subtype described as an essential component in the majority
of glutamtergic synapses in the hippocampus. Genes encoding additional components
of the presynaptic machinery were also found regulated, including Rab3A,
RIM1alpha, as well as Syntaxin1 and Synaptobrevin. Altered expression levels of
these genes were further found in the amygdala and in the retrosplenial group of
the cortex, additional regions in which Vglut2 was conditionally targeted. These
findings suggest that expression levels of Vglut2 might be important for the
maintenance of gene expression in the presynaptic machinery in the adult mouse
brain. Synapse 68:624-633, 2014. (c) 2014 Wiley Periodicals, Inc.
PMID- 25139800
TI - Using Big Data to Track Trends in Medical Practice.
PMID- 25139799
TI - Use of clarithromycin and roxithromycin and risk of cardiac death: cohort study.
AB - OBJECTIVE: To assess the risk of cardiac death associated with the use of
clarithromycin and roxithromycin. DESIGN: Cohort study. SETTING: Denmark, 1997
2011. PARTICIPANTS: Danish adults, 40-74 years of age, who received seven day
treatment courses with clarithromycin (n = 160,297), roxithromycin (n = 588,988),
and penicillin V (n = 4,355,309). MAIN OUTCOME MEASURES: The main outcome was
risk of cardiac death associated with clarithromycin and roxithromycin, compared
with penicillin V. Subgroup analyses were conducted according to sex, age, risk
score, and concomitant use of drugs that inhibit the cytochrome P450 3A enzyme,
which metabolises macrolides. RESULTS: A total of 285 cardiac deaths were
observed. Compared with use of penicillin V (incidence rate 2.5 per 1000 person
years), use of clarithromycin was associated with a significantly increased risk
of cardiac death (5.3 per 1000 person years; adjusted rate ratio 1.76, 95%
confidence interval 1.08 to 2.85) but use of roxithromycin was not (2.5 per 1000
person years; adjusted rate ratio 1.04, 0.72 to 1.51). The association with
clarithromycin was most pronounced among women (adjusted rate ratios 2.83 (1.50
to 5.36) in women and 1.09 (0.51 to 2.35) in men). Compared with penicillin V,
the adjusted absolute risk difference was 37 (95% confidence interval 4 to 90)
cardiac deaths per 1 million courses with clarithromycin and 2 (-14 to 25)
cardiac deaths per 1 million courses with roxithromycin. CONCLUSIONS: This large
cohort study found a significantly increased risk of cardiac death associated
with clarithromycin. No increased risk was seen with roxithromycin. Given the
widespread use of clarithromycin, these findings call for confirmation in
independent populations.
PMID- 25139801
TI - Reasons for Delay in Time to Initiation of Adjuvant Chemotherapy for Colon
Cancer.
AB - PURPOSE: Adjuvant chemotherapy (AC) improves survival among patients with colon
cancer (CC). Two meta-analyses have demonstrated a decrease in survival with
increasing time to AC (TTAC). Here, we examine the predominant factors leading to
delay in TTAC. METHODS: Individual medical records of 580 patients with CC who
initiated AC August 2005-November 2010 at two large academic cancer centers in
Eastern Ontario were reviewed. Information regarding patient, disease, and
treatment characteristics, including time intervals between each step in the
cancer care pathway from surgery to AC, was captured. Patients were then
categorized into three groups for comparison: (I) postoperative complication,
(II) oncologist- or patient-initiated delay, (III) no delay. These groups were
compared using chi(2) tests and one-way analysis of variance. A multivariable
logistic regression model was used to determine factors associated with TTAC > 8
weeks in all patients and in group 1 alone. RESULTS: TTAC among the three groups
was (I) 10.1 +/- 2.7 weeks, (II) 10.5 +/- 3.6 weeks, (III) 8.5 +/- 2.1 weeks (P <
.001). The only significant predictor of TTAC > 8 weeks on multivariable analysis
in group I was route of AC via central venous catheter (odds ratio [OR] = 2.4;
95% CI, 1.2 to 4.9). When multivariable analysis was performed on all patients,
the presence of postoperative complications (OR = 2.4; 95% CI, 1.6 to 3.8) and
oncologist- or patient-initiated delay were the strongest predictors of delay (OR
= 3.5; 95% CI, 2.1 to 6.0). The percentages of patients with TTAC > 8 weeks were
(I) 76.4% (n = 110), (II) 81.4% (n = 92), (III) 57.9% (n = 187). CONCLUSIONS: In
patients with no reason for delay, most experienced TTAC > 8 weeks. This likely
reflects delays in referral, consultation, and chemotherapy booking. These health
system factors are modifiable, and future quality improvement initiatives should
focus on how to reduce them.
PMID- 25139802
TI - Reply to A. Kolacevski et al.
PMID- 25139803
TI - RR interval-respiratory signal waveform modeling in human slow paced and
spontaneous breathing.
AB - Our aim was to model the dependence of respiratory sinus arrhythmia (RSA) on the
respiratory waveform and to elucidate underlying mechanisms of cardiorespiratory
coupling. In 30 subjects, RR interval and respiratory signal were recorded during
spontaneous and paced (0.1Hz/0.15Hz) breathing and their relationship was modeled
by a first order linear differential equation. This model has two parameters: a0
(related to the instantaneous degree of abdominal expansion) and a1 (referring to
the speed of abdominal expansion). Assuming that a0 represents slowly adapting
pulmonary stretch receptors (SARs) and a1 SARs in coordination with other stretch
receptors and central integrative coupling; then pulmonary stretch receptors
relaying the instantaneous lung volume are the major factor determining
cardiovagal output during inspiration. The model's results depended on breathing
frequency with the least error occurring during slow paced breathing. The role of
vagal afferent neurons in cardiorespiratory coupling may relate to
neurocardiovascular diseases in which weakened coupling among venous return,
arterial pressure, heart rate and respiration produces cardiovagal instability.
PMID- 25139804
TI - Role of striatal NMDA receptor subunits in a model of paroxysmal dystonia.
AB - Dystonia is a movement disorder in which abnormal plasticity in the basal ganglia
has been hypothesized to play a critical role. In a model of paroxysmal dystonia,
the dt(sz) mutant hamster, previous studies indicated striatal dysfunctions,
including an increased long-term potentiation (LTP). Beneficial effects were
exerted by subunit-unspecific antagonists at NMDA receptors, which blocked LTP.
NR2B subtype selective antagonists aggravated dystonia after systemic treatment
in dt(sz) hamsters, suggesting that beneficial effects involved the NR2A receptor
subtype. In the present study, NVP-AAM077, an antagonist with preferential
activity on NR2A-containing NMDA receptors, exerted significant antidystonic
effects in mutant hamsters after systemic administration (20 and 30mg/kg i.p.)
and delayed the onset of a dystonic episode after intrastriatal injections (0.12
and 0.24MUg). As shown by present electrophysiological examinations in
corticostriatal slices of dt(sz) hamsters and non-dystonic control hamsters, NVP
AAM077 (50nM) completely blocked LTP in dt(sz) slices, but did not exert
significant effects on LTP in non-dystonic controls. In contrast, the NR2B
antagonist Ro 25-6981 (1-10MUmol) reduced LTP to a lower extent in dt(sz) mutant
hamsters than in control animals. By using quantitative RT-PCR, the NR2A/NR2B
ratio was found to be increased in the striatum, but not in the cortex of mutant
hamsters in comparison to non-dystonic controls. These data indicate that NR2A
mediated activation may be involved in the pathophysiology of paroxysmal
dystonia. Since significant antidystonic effects were observed after systemic
administration of NVP-AAM077 already at well tolerated doses, antagonists with
preferential activity on NR2A-containing NMDA receptors could be interesting
candidates for the treatment of dystonia.
PMID- 25139805
TI - Novel and improved cell recognition for diagnosis.
PMID- 25139806
TI - Separating the signal from the noise: expanding flow cytometry into the sub
micron range.
PMID- 25139810
TI - New directions in management of SAPHO syndrome.
AB - To talk about SAPHO syndrome means to discuss its entity. It is a great honour to
me as guest editor to greet you and to present to you the following scientific
articles dealing with different aspects of the SAPHO syndrome. We are pleased to
welcome experts in the fields of epidemiology, etiology, clinical aspects,
imaging procedures and treatment modalities. Furthermore, I have been grateful to
be able to invite a review board to read the articles and to support the authors
with scientific remarks and interesting corrections. First, we will start with
the introduction by Prof. Dr. Koehler, University of Saarland, Germany, entitled
"From sternoclavicluar hyperostosis (SCCH) to SAPHO syndrome - a European
story?". Afterwards, Dr. Colina, PhD, Imola, Italy, with co-authors will discuss
"the latest state of the art" concerning essential clinical and radiological
characteristics of the SAPHO syndrome. The following chapter by Dr. Pfoehler,
PhD, University of Saarland, Germany, describes in detail the important
dermatological aspects of psoriatic disease and its subentity of palmoplantar
pustolosis against a etiological, diagnostic, and therapeutic background to
better understand the arthro-osteo-cutaneous character of the SAPHO syndrome. In
this context, Dr. Gilles, PhD, University Hospital of Paris, France, with co
authors then discuss the different hypotheses of immunology and the possible
autoimmune etiology of SAPHO syndrome. Furthermore, Prof. Dr. Wollheim,
University of Lund, Sweden, concludes and elucidates the genetic aspects of the
disease. With the regard to different SAPHO manifestations in the childhood, I am
thankful that Prof. Dr. Girschick, Pediatric Rheumatology Vivantes Center,
Berlin, Germany, has contributed a scientific article dealing with "non-bacterial
osteomyelitis in childhood". Last but not least, the article "Trends of SAPHO
therapy: should we content?" from Dr. Rozin, PhD, Technion Haifa, Israel, focuses
on the antirheumatic treatment modalities, including antibiotic treatment
modalities which have been investigated in case series over the last 20 years. It
was my intention that all authors touch on the genetic, diagnostic, and
therapeutic aspects of SAPHO syndrome not to cause redundancies in the
presentation but to discuss the central role of these aspects from a respectively
different viewpoint - with the aim of gaining a deep insight into the
etiopathogenesis and clinical aspects of SAPHO syndrome.
PMID- 25139811
TI - Psoriasis vulgaris and psoriasis pustulosa - epidemiology, quality of life,
comorbidities and treatment.
AB - The prevalence of psoriasis is 2-3% in European Countries, therefore psoriasis is
one of the most frequently occurring inflammatory skin diseases. Psoriasis
results from an interaction of genetic factors and environmental conditions such
as infections, smoking or intake of certain drugs. Psoriatic arthritis is
diagnosed in about 20% of patients with psoriasis. Pustular forms are much more
rarely seen and have a genetic background distinct from plaque psoriasis.
Psoriasis is associated with a multitude of comorbidities such as rheumatoid
arthritis, inflammatory bowel diseases, diabetes mellitus, obesity, hypertension
and dysfunctions in lipid metabolism. Quality of life is markedly reduced in
psoriasis patients and many of them suffer from depression and anxiety. An
interdisciplinary treatment of psoriasis and its comorbidities is therefore
essential. Today, adequate therapy according to medical guidelines is able to
heal skin lesions and to improve quality of life.
PMID- 25139812
TI - Rapid prototyped patient specific implants for reconstruction of orbital wall
defects.
AB - Defects of orbital walls can be reconstructed using implants. The authors report
a safe and accurate method to reconstruct bone defects in the orbital area using
patient specific implants. A detailed process description of computer aided
design (CAD) reconstructive surgery (CRS) is introduced in this prospective
study. The 3D volumetric virtual implant was design using MSCT data and
PTCProEngineerTM 3D software. The intact orbital cavity of twelve patients was
mirrored to the injured side. Specific ledges steered the implant into correct
place. Postoperatively the position was assessed using image fusion. One implant
(8%) was rejected due to chemical impurities, two (16%) had a false shape due to
incorrect CAD. Data of thin bone did not transfer correctly to CAD and resulted
in error. One implant (8%) was placed incorrectly. Duration of the CRS was in
average 1.17 h, correspondingly 1.57 h using intraoperative bending technique.
The CRS process has several critical stages, which are related to converting data
and to incompatibility between software. The CRS process has several steps that
need further studies. The data of thin bone may be lost and disturb an otherwise
very precise technique. The risk of incorporating impurities into the implant
must be carefully controlled.
PMID- 25139813
TI - Synthesis, physicochemical, and anticonvulsant properties of new N-Mannich bases
derived from pyrrolidine-2,5-dione and its 3-methyl analog.
AB - A series of 22 new N-[(4-phenylpiperazin-1-yl)-methyl]-3-methyl-pyrrolidine-2,5
dione and pyrrolidine-2,5-dione derivatives were synthesized and evaluated for
their anticonvulsant activities in the maximum electroshock (MES) and
subcutaneous pentylenetetrazole (scPTZ) seizure tests after intraperitoneal
injection into mice. The neurotoxicity was determined applying the rotarod test.
The in vivo results in mice showed that seven compounds were effective in the MES
or/and scPTZ seizure tests. The quantitative evaluation in both tests after i.p.
administration into mice revealed that the most active compounds were N-[{4-(3,4
dichlorophenyl)-piperazin-1-yl}-methyl]-3-methylpyrrolidine-2,5-dione (12) with
ED50 = 16.13 mg/kg (MES), ED50 = 133.99 mg/kg (scPTZ) and N-[{4-(3,4
dichlorophenyl)-piperazin-1-yl}-methyl]-pyrrolidine-2,5-dione (23) with ED50 =
37.79 mg/kg (MES), ED50 = 128.82 mg/kg (scPTZ), whereas N-[{4-(3
trifluoromethylphenyl)-piperazin-1-yl}-methyl]-pyrrolidine-2,5-dione (24) was
effective only in the MES test with ED50 = 16.37 mg/kg. These molecules showed
higher potency and also lower neurotoxicity than the reference antiepileptic
drugs such as ethosuximide and valproic acid.
PMID- 25139814
TI - Hierarchical self-assembly of supramolecular hydrophobic metallacycles into
ordered nanostructures.
AB - We describe herein the hierarchical self-assembly of discrete supramolecular
metallacycles into ordered fibers or spherical particles through multiple
noncovalent interactions. A new series of well-defined metallacycles decorated
with long alkyl chains were obtained through metal-ligand interactions, which
were capable of aggregating into ordered fibroid or spherical nanostructures on
the surface, mostly driven by hydrophobic interactions. In-depth studies
indicated that the morphology diversity was originated from the structural
information encoded in the metallacycles, including the number of alkyl chains
and their spatial orientation. Interestingly, the morphology of the metallacycle
aggregates could be tuned by changing the solvent polarity. These findings are of
special significance since they provide a simple yet highly controllable approach
to prepare ordered and tunable nanostructures from small building blocks by means
of hierarchical self-assembly.
PMID- 25139815
TI - Effects of solvent evaporation time on immediate adhesive properties of universal
adhesives to dentin.
AB - OBJECTIVE: To evaluate the microtensile bond strengths (MUTBS) and nanoleakage
(NL) of three universal or multi-mode adhesives, applied with increasing solvent
evaporation times. METHODS: One-hundred and forty caries-free extracted third
molars were divided into 20 groups for bond strength testing, according to three
factors: (1) Adhesive - All-Bond Universal (ABU, Bisco, Inc.), Prime&Bond Elect
(PBE, Dentsply), and Scotchbond Universal Adhesive (SBU, 3M ESPE); (2) Bonding
strategy - self-etch (SE) or etch-and-rinse (ER); and (3) Adhesive solvent
evaporation time - 5s, 15s, and 25s. Two extra groups were prepared with ABU
because the respective manufacturer recommends a solvent evaporation time of 10s.
After restorations were constructed, specimens were stored in water (37 degrees
C/24h). Resin-dentin beams (0.8mm(2)) were tested at 0.5mm/min (MUTBS). For NL,
forty extracted molars were randomly assigned to each of the 20 groups. Dentin
disks were restored, immersed in ammoniacal silver nitrate, sectioned and
processed for evaluation under a FESEM in backscattered mode. Data from MUTBS
were analyzed using two-way ANOVA (adhesive vs. drying time) for each strategy,
and Tukey's test (alpha=0.05). NL data were computed with non-parametric tests
(Kruskal-Wallis and Mann-Whitney tests, alpha=0.05). RESULTS: Increasing solvent
evaporation time from 5s to 25s resulted in statistically higher mean MUTBS for
all adhesives when used in ER mode. Regarding NL, ER resulted in greater NL than
SE for each of the evaporation times regardless of the adhesive used. A solvent
evaporation time of 25s resulted in the lowest NL for SBU-ER. SIGNIFICANCE:
Residual water and/or solvent may compromise the performance of universal
adhesives, which may be improved with extended evaporation times.
PMID- 25139816
TI - What can fibromyalgia teach us about chronic pain? An emblematic condition to
discuss mind and body concepts, predictive medicine and assessment of chronic
condition management.
PMID- 25139817
TI - More ubiquitous effects from non-pharmacologic than from pharmacologic treatments
for fibromyalgia syndrome: a meta-analysis examining six core symptoms.
AB - This study aimed to characterize and compare the efficacy profile on six
fibromyalgia syndrome (FM) core symptoms associated with pharmacologic and non
pharmacologic treatments. We screened PubMed, Embase and the Cochrane Library for
FM articles from 1990 to September 2012 to analyse randomized controlled trials
comparing pharmacologic or non-pharmacologic treatments to placebo or sham.
Papers including assessments of at least 2 of the 6 main FM symptom domains -
pain, sleep disturbance, fatigue, affective symptoms (depression/anxiety),
functional deficit and cognitive impairment - were selected for analysis. Studies
exploring pharmacologic approaches (n = 21) were mainly dedicated to treating a
small number of dimensions, mostly pain. They were of good quality but were not
prospectively designed to simultaneously document efficacy for the management of
multiple core FM symptom domains. Only amitriptyline demonstrated a significant
effect on as many as three core FM symptoms, but it exhibited many adverse
effects and was subject to early tachyphylaxis. Studies involving non
pharmacologic approaches (n = 64) were typically of poorer quality but were more
often dedicated to multidimensional targets. Pool therapy demonstrated
significant effects on five symptom domains, repetitive transcranial magnetic
stimulation on four domains, balneotherapy on three domains and exercise,
cognitive behaviour therapy and massage on two domains each. Differences between
pharmacologic and non-pharmacologic approaches may be related to different modes
of action, tolerability profiles and study designs. Very few drugs in well
designed clinical trials have demonstrated significant relief for multiple FM
symptom domains, whereas non-pharmacologic treatments with weaker study designs
have demonstrated multidimensional effects. Future therapeutic trials for FM
should prospectively examine each of the core domains and should attempt to
combine pharmacologic and non-pharmacologic therapies in well-designed clinical
trials.
PMID- 25139818
TI - Motor training-induced cortical plastic changes and its disruption by chronic
pain: a puzzle with more pieces than expected.
PMID- 25139819
TI - Introduction of a national herpes zoster (shingles) immunization programme and
impact on neuropathic pain.
PMID- 25139820
TI - Mitochondrial dysfunction as a central event for mechanisms underlying insulin
resistance: the roles of long chain fatty acids.
AB - Insulin resistance is characterized by hyperglycaemia, dyslipidaemia and
oxidative stress prior to the development of type 2 diabetes mellitus. To date, a
number of mechanisms have been proposed to link these syndromes together, but it
remains unclear what the unifying condition that triggered these events in the
progression of this metabolic disease. There have been a steady accumulation of
data in numerous experimental studies showing the strong correlations between
mitochondrial dysfunction, oxidative stress and insulin resistance. In addition,
a growing number of studies suggest that the raised plasma free fatty acid level
induced insulin resistance with the significant alteration of oxidative
metabolism in various target tissues such as skeletal muscle, liver and adipose
tissue. In this review, we herein propose the idea of long chain fatty acid
induced mitochondrial dysfunctions as one of the key events in the
pathophysiological development of insulin resistance and type 2 diabetes. The
accumulation of reactive oxygen species, lipotoxicity, inflammation-induced
endoplasmic reticulum stress and alterations of mitochondrial gene subset
expressions are the most detrimental that lead to the developments of aberrant
intracellular insulin signalling activity in a number of peripheral tissues,
thereby leading to insulin resistance and type 2 diabetes.
PMID- 25139821
TI - A rare disorder mimics otitis media: Langerhans cell histiocytosis of the
temporal bone in a child with interstitial pulmonary fibrosis.
AB - Langerhans cell histiocytosis (LCH) is a rare disease ranging from a benign to a
rapidly fatal condition affecting young children predominantly, and is
characterized by an abnormal clonal proliferation of Langerhans cells. We report
a case of a 3-year-old child presenting with a 1-year history of otorrhea and
otorrhagia followed by a 6-month history of postauricular swelling in the right
ear. Imaging demonstrated a large mass of organized tissue. A biopsy was
conducted, and the diagnosis of LCH was confirmed by histopathological and
immunohistochemical examination. The child was treated with a 12-month course of
vinblastine chemotherapy with prednisolone. No clinical evidence of recurrence
was noticed after 3 years of follow-up. This rare case highlights the importance
for otolaryngologists to keep LCH in mind for differential diagnosis in very
young patients with symptoms and signs suggestive of acute mastoiditis or chronic
otitis media.
PMID- 25139822
TI - Mechanisms underlying chronic whiplash: contributions from an incomplete spinal
cord injury?
AB - OBJECTIVE: To explore the association between findings on advanced, but
available, magnetic resonance imaging (MRI) sequences of the cervical spinal cord
and muscular system, in tandem with biomechanical measures of maximum volitional
plantar flexion torques as a proxy for a mild incomplete spinal cord injury.
DESIGN: Observational case series. SETTING: University research laboratory.
SUBJECTS: Three patients with chronic whiplash and one patient with history of
whiplash injury but no current symptoms. METHODS: We measured lower extremity
muscle fat, morphological changes in descending spinal cord pathways with
advanced MRI applications and maximal activation of the plantar flexors. RESULTS:
Larger magnitudes of lower extremity muscle fat corresponded to altered spinal
cord anatomy and reductions in the ability to maximally activate plantar flexor
torques in the three subjects with chronic whiplash. Such findings were not
present in the recovered participant. CONCLUSIONS: The potential value of MRI to
quantify neuromuscular degeneration in chronic whiplash is recognized. Larger
scaled prospective studies are warranted before stronger conclusions can be
drawn.
PMID- 25139823
TI - High nuclear expression levels of histone-modifying enzymes LSD1, HDAC2 and SIRT1
in tumor cells correlate with decreased survival and increased relapse in breast
cancer patients.
AB - BACKGROUND: Breast cancer is a heterogeneous disease with a highly variable
clinical outcome in which both genetic and epigenetic changes have critical
roles. We investigated tumor expression levels of histone-modifying enzymes LSD1,
HDAC2 and SIRT1 in relation with patient survival and tumor relapse in a
retrospective cohort of 460 breast cancer patients. Additionally, we correlated
expression levels with tumor differentiation and tumor cell proliferation.
METHODS: Immunohistochemical staining for LSD1, HDAC2 and SIRT1 was performed on
tissue microarrays of tumor and corresponding normal formalin-fixed paraffin
embedded tissues from breast cancer patients. Median nuclear expression levels in
tumor tissues were used to divide the patients into low and high expression
categories. In combined expression analyses, patients were divided into four
subgroups: 1, all enzymes below-median; 2, one enzyme above-median; 3, two
enzymes above-median; 4, all three enzymes above-median. The Cox proportional
hazard model was used for univariate and multivariate survival analyses. The
Pearson Chi-square method was used to assess correlation of combined expression
levels with tumor cell proliferation and tumor differentiation. RESULTS:
Expression of LSD1 and SIRT1, but not of HDAC2, was significantly increased in
tumor tissues compared to their normal counterparts (both p < 0.001).
Multivariate survival analyses identified SIRT1 as independent prognostic factor
for relapse-free survival (RFS) with a hazard ratio (HR) of 1.34 (95% CI = 1.04
1.74, p = 0.02). For overall survival (OS), no significant differences were found
when the individual enzymes were analyzed. Analyses of combined expression levels
of the three histone-modifying enzymes correlated with OS (p = 0.03) and RFS (p =
0.006) with a HR of respectively 1.49 (95% CI = 1.07-2.08) and 1.68 (95% CI =
1.16-2.44) in multivariate analyses and were also related to tumor
differentiation (p < 0.001) and tumor cell proliferation (p = 0.002).
CONCLUSIONS: When the combined expression levels were analyzed, high expression
of LSD1, HDAC2 and SIRT1 showed shorter patient survival time and shorter time to
tumor relapse and correlated with poor tumor differentiation and a high level of
tumor cell proliferation. Expression of these histone-modifying enzymes might
therefore be involved in breast cancer pathogenesis.
PMID- 25139825
TI - Glucagon in the artificial pancreas: supply and marketing challenges.
AB - The use of glucagon, in conjunction with insulin, in a dual chamber pump
(artificial pancreas, AP) is a working goal for multiple companies and
researchers. However, capital investment to create, operate, and maintain
facilities with sufficient scale to produce enough glucagon to treat millions of
patients, at a level of profit that makes it feasible, will be substantial. It
can be assumed that the marketplace will expect the daily cost of glucagon (to
the consumer) to be similar to the daily cost of insulin. After one subtracts
wholesaler and pharmacy markup, there may be very few dollars remaining for the
drug company to cover profit, capital expenditures, marketing, burden, and other
costs. Without the potential for adequate margins, manufacturers may not be
willing to take the risk. Assuming that the projections discussed in this article
are in the right ballpark, advance planning for the supply for glucagon needs to
start today and not wait for the AP to come to market.
PMID- 25139826
TI - Efficient quantification and characterization of bacterial outer membrane derived
nano-particles with flow cytometric analysis.
AB - There currently exists no efficient and easy method for size profiling and
counting of membranous nano-scale particles, such as bacterial outer membrane
vesicles (OMVs). We present here a cost-effective and fast method capable of
profiling and counting small sample volumes of nano-scale membranous vesicles
with standard laboratory equipment without the need for any washing steps. OMV
populations of different bacterial species are compared and even subpopulations
of OMVs can be identified after a simple labelling procedure. Counting is
possible over three orders of magnitude without any changes to the protocol.
Protein contaminations do not alter the described measurements.
PMID- 25139827
TI - Reply to a comment by Ludbrook, Holmes, and Stockwell: gender differences in
alcohol demand.
PMID- 25139828
TI - Effect of different drying methods on chlorophyll, ascorbic acid and antioxidant
compounds retention of leaves of Hibiscus sabdariffa L.
AB - BACKGROUND: Use of the indigenous, easily accessible leafy vegetable roselle
(Hibiscus sabdariffa L.) for value addition is gaining impetus as its nutritive
and nutraceutical compounds are exposed by investigations. Being a perishable,
storage is challenging, hence different methods of drying have been an attractive
alternative for its postharvest usage in foods without much compromising its
quality and antioxidant potential. RESULTS: Room- and freeze-dried samples were
found to have best quality in terms of colour, total flavonoid content (18.53 +/-
2.39 and 18.66 +/- 1.06 g kg(-1) respectively), total phenolic content (17.76 +/-
1.93 and 18.91 +/- 0.48 g kg(-1)), chlorophyll content (1.59 +/- 0.001 and 1.55
+/- 0.001 g kg(-1)) and ascorbic acid content (11.11 +/- 1.04 and 8.92 +/- 0.94 g
kg(-1)) compared with those subjected to infrared, crossflow, microwave, oven or
sun drying. Samples treated by room and freeze drying retained maximum
antioxidant potential as shown by the phosphomolybdate method and the 2,2
diphenyl-1-picrylhydrazyl free radical-scavenging activity and ferric-reducing
antioxidant power assays. Cold water and hot water extracts showed significantly
higher total phenolic content and total antioxidant activity owing to the greater
solubility of phenolics and destruction of cellular components in polar solvents
than in organic solvents. CONCLUSION: The data obtained show the potential for
retaining quality parameters of roselle leaf under suitable drying methods.
PMID- 25139829
TI - MicroRNA-145 as one negative regulator of astrogliosis.
AB - Astrogliosis occurs at the lesion site within days to weeks after spinal cord
injury (SCI) and involves the proliferation and hypertrophy of astrocytes,
leading to glia scar formation. Changes in gene expression by deregulated
microRNAs (miRNAs) are involved in the process of central nervous system
neurodegeneration. Here, we report that mir-145, a miRNA enriched in rat spinal
neurons and astrocytes, was downregulated at 1 week and 1 month after SCI. Our in
vitro studies using astrocytes prepared from neonatal spinal cord tissues
indicated that potent inflammagen lipopolysaccharide downregulated mir-145
expression in astrocytes, suggesting that SCI-triggered inflammatory signaling
pathways could play the inhibitory role in astrocytic mir-145 expression. To
induce overexpression of mir-145 in astrocytes at the spinal cord lesion site, we
developed a lentivirus-mediated pre-miRNA delivery system using the promoter of
glial fibrillary acidic protein (GFAP), an astrocyte-specific intermediate
filament. The results indicated that astrocyte-specific overexpression of mir-145
reduced astrocytic cell density at the lesion border of the injured spinal cord.
In parallel, overexpression of mir-145 reduced the size of astrocytes and the
number of related cell processes, as well as cell proliferation and migration.
Through a luciferase reporter system, we found that GFAP and c-myc were the two
potential targets of mir-145 in astrocytes. Together, the findings demonstrate
the novel role of mir-145 in the regulation of astrocytic dynamics, and reveal
that the downregulation of mir-145 in astrocytes is a critical factor inducing
astrogliosis after SCI. GLIA 2015;63:194-205.
PMID- 25139830
TI - The brassinosteroid signaling network-a paradigm of signal integration.
AB - Many hormonal and environmental signals regulate common cellular and
developmental processes in plants. While the molecular pathways that transduce
these signals have each been studied in detail, how these pathways are wired into
regulatory networks to provide the coordinated responses has remained an
outstanding question. Recent studies of the brassinosteroid signaling network
have revealed extensive signal integration through direct interactions between
components of different signaling pathways. In particular, a circuit of
interacting transcription regulators integrates many signaling pathways to enable
coordinated and coherent regulation of seedling morphogenesis by hormonal and
environmental signals. The recent studies support an emerging theme that complex
networks of highly integrated signaling pathways underlie the high levels of
developmental plasticity and environmental adaptability of plants.
PMID- 25139831
TI - Transport of ginkgolides with different lipophilicities based on an hCMEC/D3 cell
monolayer as a blood-brain barrier cell model.
AB - AIMS: In this report, the transport of ginkgolides with different lipophilicities
was investigated using an hCMEC/D3 cell monolayer as a blood-brain barrier (BBB)
cell model in vitro in an attempt to explain ginkgolide transport path mediated
by lipophilicity. MAIN METHODS: The log P values of ginkgolides were determined
by measuring the distribution of the molecule between oil and water.
Additionally, the cytotoxicity of ginkgolides on hCMEC/D3 cells was assayed with
the MTT method. Ginkgolide contents were determined with an ultra performance
liquid chromatograph equipped with an evaporative light scattering detector (ULPC
ELSD) method. Apparent permeability coefficients (Papp) and efflux ratios (PappBL
>AP/PappAP->BL) were then calculated to describe the transport characteristics of
ginkgolide. KEY FINDINGS: The transport of ginkgolide A, ginkgolide B, ginkgolide
C, and ginkgolide J across the hCMEC/D3 cell monolayer was non-directional.
Additionally, ginkgolide C transport on the cell monolayer was time- and
concentration-dependent in the paracellular pathway controlled by cytochalasin D
(a tight junction modulator). The transport of ginkgolide N, ginkgolide L, and
ginkgolide K across the cell monolayer displayed clear directionality at low
ginkgolide concentrations. This behavior indicated that the transport of
ginkgolide N, ginkgolide L, and ginkgolide K was influenced by the transcellular
pathway containing an efflux protein accompanied by the paracellular pathway for
passive diffusion. Additionally, the transport of ginkgolide K was increased
significantly by co-culturing with a P-gp inhibitor. SIGNIFICANCE: These findings
provide important information for elucidating ginkgolide transport pathways and
may be beneficial for the design of ginkgolide molecules with high
neuroprotective effects.
PMID- 25139832
TI - Induction of TRPV5 expression by small activating RNA targeting gene promoter as
a novel approach to regulate cellular calcium transportation.
AB - AIM: Promoter-targeted small activating RNAs (saRNAs) have been shown to be able
to induce target gene expression, a mechanism known as RNA activation (RNAa). The
present study tested whether saRNA can induce the overexpression of TRPV5 in
human cells derived from the kidney and subsequently manipulate cell calcium
uptake. MAIN METHODS: Three saRNAs complementary to the TRPV5 promoter were
synthesized and transfected into cells. TRPV5 expression at the RNA and protein
levels was analyzed by quantitative real-time PCR and Western blotting
respectively. For functional study, transcellular Ca(2+) transportation was
tested by fura-2 analysis. Dihydrotestosterone (DHT), a suppressor of cellular
calcium transportation, was administered to challenge the activating effect of
selected saRNA. KEY FINDINGS: One of these synthesized saRNAs, ds-2939,
significantly induced the expression of TRPV5 at both mRNA and protein levels.
Fura-2 analysis revealed that the intracellular Ca(2+) concentration was elevated
by ds-2939. DHT treatment reduced transmembrane Ca(2+) transport, which was
partially antagonized by ds-2939. SIGNIFICANCE: Our results suggest that a saRNA
targeting TRPV5 promoter can be utilized to manipulate the transmembrane Ca(2+)
transport by upregulating the expression of TRPV5 and may serve as an alternative
for the treatment of Ca(2+) balance-related diseases.
PMID- 25139833
TI - Prostaglandin E2 produced by inducible COX-2 and mPGES-1 promoting cancer cell
proliferation in vitro and in vivo.
AB - AIM: Many cancers originate and flourish in a prolonged inflammatory environment.
Our aim is to understand the mechanisms of how the pathway of prostaglandin E2
(PGE2) biosynthesis and signaling can promote cancer growth in inflammatory
environment at cellular and animal model levels. MAIN METHODS: In this study, a
chronic inflammation pathway was mimicked with a stable cell line that over
expressed a novel human enzyme consisting of cyclooxygenase isoform-2 (COX-2)
linked to microsomal (PGE2 synthase-1 (mPGES-1)) for the overproduction of
pathogenic PGE2. This PGE2-producing cell line was co-cultured and co-implanted
with three human cancer cell lines including prostate, lung, and colon cancers in
vitro and in vivo, respectively. KEY FINDINGS: Increases in cell doubling rates
for the three cancer cell types in the presence of the PGE2-producing cell line
were clearly observed. In addition, one of the four human PGE2 subtype receptors,
EP1, was used as a model to identify PGE2-signaling involved in promoting the
cancer cell growth. This finding was further proven in vivo by co-implanting the
PGE2-producing cells line and the EP1-positive cancer cells into the immune
deficient mice, after that, it was observed that the PGE2-producing cells
promoted all three types of cancer formation in the mice. SIGNIFICANCE: This
study clearly demonstrated that the human COX-2 linked to mPGES-1 is a pathway
that, when mediated by the EP, is linked to promoting cancer growth in a chronic
inflammatory environment. The identified pathway could be used as a novel target
for developing and advancing anti-inflammation and anti-cancer interventions.
PMID- 25139834
TI - Effects of intravenous cariporide on release of norepinephrine and myoglobin
during myocardial ischemia/reperfusion in rabbits.
AB - AIMS: To examine the effects of cariporide, a Na(+)/H(+) exchanger-1 inhibitor,
on cardiac norepinephrine (NE) and myoglobin release during myocardial
ischemia/reperfusion by applying a microdialysis technique to the rabbit heart.
MAIN METHODS: In anesthetized rabbits, two dialysis probes were implanted into
the left ventricular myocardium and were perfused with Ringer's solution.
Cariporide (0.3mg/kg) was injected intravenously, followed by occlusion of the
left circumflex coronary artery. During 30-min coronary occlusion followed by 30
min reperfusion, four consecutive 15-min dialysate samples (two during ischemia
and two during reperfusion) were collected in vehicle and cariporide-treated
groups. Dialysate myoglobin and NE concentrations were measured by
immunochemistry and high-performance liquid chromatography, respectively. KEY
FINDINGS: Dialysate myoglobin and NE concentrations increased significantly
during myocardial ischemia/reperfusion in both vehicle and cariporide-treated
groups (P<0.01 vs. baseline). In cariporide-treated group, dialysate myoglobin
concentrations were significantly lower than those in vehicle group throughout
ischemia/reperfusion (P<0.01 at 0-15 min of ischemia, P<0.05 at 15-30 min of
ischemia, P<0.01 at 0-15 min of reperfusion, and P<0.01 at 15-30 min of
reperfusion). However, dialysate NE concentrations in cariporide-treated group
were lower than those in vehicle group only during ischemia (P<0.01 at 0-15 min
of ischemia, and P<0.05 at 15-30 min of ischemia). SIGNIFICANCE: When
administered before ischemia, cariporide reduces myoglobin release during
ischemia/reperfusion and decreases NE release during ischemia.
PMID- 25139835
TI - Discounting of delayed rewards: (A)theoretical interpretation of the Kirby
questionnaire.
AB - 111 Participants, recruited from Amazon's MTurk worker pool, completed Kirby's
(2009) monetary choice questionnaire, which involves choosing between immediate,
but smaller rewards and delayed, but larger rewards. Individual participants'
responses were scored in three ways: first, by calculating the proportion of
choices of the delayed rewards; second; using the scoring procedure described by
Kirby et al. (1999) to estimate discounting rate (i.e., the value of the k
parameter in a hyperbolic discounting function); and third, using logistic
regression to estimate discounting rate (Wileyto et al., 2004). Individuals'
scores calculated using the proportion measure and the logarithms of their
estimated k values were very strongly correlated (rs>.97). In addition, the
proportions of choices of small, medium, and large amounts of the delayed rewards
were strongly correlated (rs>.80). Taken together, these results suggest that the
relative ease of calculating the proportion measure does not require sacrificing
reliability. Moreover, the proportion measure is atheoretical and very easy to
calculate whereas estimating an individual's discounting rate requires assuming a
theoretical model that may not be appropriate. Significant differences in the
proportion of delayed reward choices were observed between the small, medium, and
large delayed reward amounts, with smaller rewards being discounted more steeply
than larger ones, replicating previous findings of magnitude effects. These
results provide further validation of the proportion of delayed reward choices on
the Kirby questionnaire as a measure of individual and group differences in
discounting.
PMID- 25139836
TI - Genome size estimates for crustaceans using Feulgen image analysis densitometry
of ethanol-preserved tissues.
AB - Crustaceans are enormously diverse both phylogenetically and ecologically, but
they remain substantially underrepresented in the existing genome size database.
An expansion of this dataset could be facilitated if it were possible to obtain
genome size estimates from ethanol-preserved specimens. In this study, two tests
were performed in order to assess the reliability of genome size data generated
using preserved material. First, the results of estimates based on flash-frozen
versus ethanol-preserved material were compared across 37 species of crustaceans
that differ widely in genome size. Second, a comparison was made of specimens
from a single species that had been stored in ethanol for 1-14 years. In both
cases, the use of gill tissue in Feulgen image analysis densitometry proved to be
a very viable approach. This finding is of direct relevance to both new studies
of field-collected crustaceans as well as potential studies based on existing
collections.
PMID- 25139837
TI - Interplay between plasmid-mediated and chromosomal-mediated fluoroquinolone
resistance and bacterial fitness in Escherichia coli.
AB - OBJECTIVES: The aim of this study was to analyse the interplay among plasmid
mediated qnr genes, alone or in combination with multiple chromosomal-mediated
fluoroquinolone (FQ) resistance determinants, susceptibility to FQs and bacterial
fitness in an isogenic Escherichia coli collection. METHODS: E. coli ATCC 25922
was used to modify or delete chromosomal genes. qnr genes were cloned into the
pBK-CMV vector. The MICs of FQs were determined by microdilution. Mutant
prevention concentration and frequency of mutants were evaluated. Bacterial
fitness was analysed using DeltalacZ system competition assays using in vitro and
in vivo models. RESULTS: The relationships between the number of resistance
mutations and bacterial fitness were complex. With specific combinations of
resistance mechanisms the addition of a new resistance mutation was shown to
improve bacterial fitness. qnrA1 caused a decrease in fitness (7%-21%) while
qnrS1 caused an increase in fitness (9%-21%) when combined with chromosomal
mutations. We identified susceptible triple mutants in which the acquisition of a
fourth resistance mutation significantly increased fitness and at the same time
reached the clinical resistance level (the acquisition of qnrS1 in a S83L + D87N
+ DeltamarR genetic background). A strong correlation with the production of
reactive oxygen species, as well as changes in susceptibility, was observed
following treatment with ciprofloxacin. CONCLUSIONS: Our data indicate that there
may be critical stages (depending on the genotype) in resistance development,
including chromosomal- and plasmid-mediated mechanisms, at which some low-fitness
mutants below the resistance breakpoint are able to evolve clinical resistance
with just one or two mutations, and show increased fitness.
PMID- 25139838
TI - MacABCsm, an ABC-type tripartite efflux pump of Stenotrophomonas maltophilia
involved in drug resistance, oxidative and envelope stress tolerances and biofilm
formation.
AB - OBJECTIVES: To characterize a five gene cluster, macRS-macABCsm, in
Stenotrophomonas maltophilia. METHODS: The presence of macABCsm operon was
verified by RT-PCR. The substrate spectrum of the MacABCsm efflux pump was
investigated by mutant construction and susceptibility testing. The physiological
role of MacABCsm was assessed by comparing the growth of wild-type and macABCsm
mutant under different stresses. To examine the regulatory role of the two
component regulatory system (TCS) macRS in the expression of macABCsm operon,
mutant construction, quantitative RT-PCR and susceptibility testing were
employed. RESULTS: macAsm, macBsm and macCsm genes formed a three-membered
operon. The MacABCsm efflux pump extruded macrolides, aminoglycosides and
polymyxins and contributed to oxidative and envelope stress tolerances and
biofilm formation. Inactivation of macRS TCS hardly influenced the expression of
macABCsm operon and the antimicrobial susceptibility. CONCLUSIONS: The MacABCsm
pump has physiological roles in protecting S. maltophilia from the attack of
oxidative and envelope stresses and in biofilm formation, which may be the reason
why it can be constitutively expressed in the absence of antibiotics and is
highly conserved in S. maltophilia isolates isolated from different environmental
niches. However, the constitutive expression of macABCsm contributes to the
intrinsic resistance of S. maltophilia to macrolides, aminoglycosides and
polymyxins.
PMID- 25139839
TI - Prophylactic treatment with a novel bioadhesive gel formulation containing
aciclovir and tenofovir protects from HSV-2 infection.
AB - OBJECTIVES: Over-the-counter access to an inexpensive, effective topical
microbicide could reduce the transmission of HIV and would increase women's
control over their health and eliminate the need to obtain their partners'
consent for prophylaxis. Chronic infection with herpes simplex virus 2 (HSV-2),
also known as human herpes virus 2, has been shown to facilitate HIV infection
and speed the progression to immunodeficiency disease. Our objective is to
develop a drug formulation that protects against both HSV-2 and HIV infection and
adheres to the vaginal surface with extended residence time. METHODS: We
developed a formulation using two approved antiviral active pharmaceutical
ingredients, aciclovir and tenofovir, in a novel bioadhesive vaginal delivery
platform (designated SR-2P) composed of two polymers, poloxamer 407 NF
(Pluronic((r)) F-127) and polycarbophil USP (Noveon((r)) AA-1). The efficacy of
the formulation to protect from HSV-2 infection was tested in vitro and in vivo.
In addition to its efficacy, it is essential for a successful microbicide to be
non-irritating to the vaginal mucosa. We therefore tested our SR-2P platform gel
in the FDA gold-standard microbicide safety model in rabbits and also in a rat
vaginal irritation model. RESULTS: Our studies indicated that SR-2P containing 1%
aciclovir and 5% tenofovir protects (i) Vero cells from HSV-2 infection in vitro
and (ii) mice from HSV-2 infection in vivo. Our results further demonstrated that
SR-2P was not irritating in either vaginal irritation model. CONCLUSIONS: We
conclude that SR-2P containing aciclovir and tenofovir may be a suitable
candidate microbicide to protect humans from vaginal HSV-2 infection.
PMID- 25139840
TI - Pharmacokinetics of caspofungin in ICU patients.
AB - OBJECTIVES: Caspofungin is used for treatment of invasive fungal infections. As
the pharmacokinetics (PK) of antimicrobial agents in critically ill patients can
be highly variable, we set out to explore caspofungin PK in ICU patients.
METHODS: ICU patients receiving caspofungin were eligible. Patients received a
loading dose of 70 mg followed by 50 mg daily (70 mg if body weight >80 kg); they
were evaluable upon completion of the first PK curve at day 3. Additionally,
daily trough samples were taken and a second PK curve was recorded at day 7. PK
analysis was performed using a standard two-stage approach. RESULTS: Twenty-one
patients were evaluable. Median (range) age and body weight were 71 (45-80) years
and 75 (50-99) kg. PK sampling on day 3 (n = 21) resulted in the following median
(IQR) parameters: AUC0-24 88.7 (72.2-97.5) mg.h/L; Cmin 2.15 (1.40-2.48) mg/L;
Cmax 7.51 (6.05-8.17) mg/L; V 7.72 (6.12-9.01) L; and CL 0.57 (0.54-0.77) L/h. PK
sampling on day 7 (n = 13) resulted in AUC0-24 107.2 (90.4-125.3) mg.h/L, Cmin
2.55 (1.82-3.08) mg/L, Cmax 8.65 (7.16-9.34) mg/L, V 7.03 (5.51-7.73) L and CL
0.54 (0.44-0.60) L/h. We did not identify any covariates significantly affecting
caspofungin PK in ICU patients (e.g. body weight, albumin, liver function).
Caspofungin was well tolerated and no unexpected side effects were observed.
CONCLUSIONS: Caspofungin PK in ICU patients showed limited intraindividual and
moderate interindividual variability, and caspofungin was well tolerated. A
standard two-stage approach did not reveal significant covariates. Our study
showed similar caspofungin PK parameters in ICU patients compared with non
critically ill patients.
PMID- 25139841
TI - Correlation of cetuximab-induced skin rash and outcomes of solid tumor patients
treated with cetuximab: a systematic review and meta-analysis.
AB - BACKGROUND: We performed a systematic review and meta-analysis of the correlation
between cetuximab-induced skin rash and outcomes of solid tumor patients treated
with cetuximab. PATIENTS AND METHODS: Eligible studies included phase I, II and
III trials of patients with solid tumors on cetuximab; describing events of skin
rash and correlating skin rash with overall survival (OS), progression free
survival (PFS) and/or overall response rate (ORR). RESULTS: Our search strategy
yielded 409 potentially relevant citations on CETUXIMAB from Pubmed/Medline,
CENTRAL Cochrane registry and ASCO meeting library. After exclusion of ineligible
studies, a total of 13 clinical trials were considered eligible for the meta
analysis, including 4 phase III trials, 8 phase II trials and one phase I trial.
The occurrence of cetuximab-induced rash in patients was highly associated with
improvements in PFS (HR=0.74; 95% CI: 0.63-0.86, P<0.0002), OS (HR=0.60; 95% CI:
0.47-0.76, P<0.0001), and ORR (RR=1.51, 95% CI: 1.26-1.81, P<0.00001), as
compared to patients without rash. Exploratory subgroup analysis showed no effect
of tumor types on the RR of ORR. CONCLUSIONS: Our meta-analysis has demonstrated
that cetuximab-induced rash is associated with a significantly improved OS, PFS
and ORR. Cetuximab-induced skin rash may represent a prognostic factor in
patients with advanced solid tumors.
PMID- 25139842
TI - 1-Acetyl-3,5-diaryl-4,5-dihydro(1H)pyrazoles: exhibiting anticancer activity
through intracellular ROS scavenging and the mitochondria-dependent death
pathway.
AB - A series of 17 analogs of 1-acetyl-4,5-dihydro(1H)pyrazoles (JP-1 to JP-17)
bearing two aromatic rings at positions 3 and 5, either of which ought to be
heterocyclic, were synthesized and evaluated for their anti-proliferative
potential against breast cancer (MCF-7 and T-47D) and lung cancer (H-460 and A
549) cell lines for the first time. JP-1-7, -10, -11, -14, and -15 were observed
to exhibit significant anti-proliferative activity against MCF-7 cells. Some
notions about structure-activity relationships are reported. The investigated
compounds were found to lower the intracellular reactive oxygen species in the H2
DCFDA assay and also caused mitochondria-dependent cell death in the MCF-7 cell
line, indicating a plausible mechanism of their anticancer effect.
PMID- 25139843
TI - Carbapenems and piperacillin/tazobactam for the treatment of bacteremia caused by
extended-spectrum beta-lactamase-producing Proteus mirabilis.
AB - This study was intended to delineate the role of carbapenems and
piperacillin/tazobactam in treating bacteremia caused by extended-spectrum beta
lactamase (ESBL)-producing Proteus mirabilis. We performed a multicenter and
retrospective study of the patients with ESBL-producing P. mirabilis bacteremia.
The outcomes of the patients treated by piperacillin/tazobactam or a carbapenem
for at least 48 hours and the MICs of the prescribed drugs for these isolates
were analyzed. Forty-seven patients with available clinical data were included.
The overall 30-day mortality rate was 29.8%. All available isolates (n = 44) were
susceptible to ertapenem, meropenem, and doripenem, and 95.6% were susceptible to
piperacillin/tazobactam; however, only 11.4% of the isolates were susceptible to
imipenem. Among the 3 patients infected with isolates exhibiting non
susceptibility to imipenem (MIC >=2 mg/L) who were treated with imipenem, none
died within 28 days. The 30-day (14.3% versus 23.1%, P = 0.65) or in-hospital
(19.1% versus 30.8%, P = 0.68) mortality rate of 21 patients treated by a
carbapenem was lower than that of 13 treated by piperacillin/tazobactam. However,
among those treated by piperacillin/tazobactam, the mortality rate of those
infected by the isolates with lower piperacillin/tazobactam MICs (<=0.5/4 mg/L)
was lower than that of the isolates with MICs of >=1/4 mg/L (0%, 0/7 versus 60%,
3/5; P = 0.045). ESBL-producing P. mirabilis bacteremia is associated with
significant mortality, and carbapenem therapy could be regarded as the drugs of
choice. The role of piperacillin/tazobactam, especially for the infections due to
the isolates with an MIC <=0.5/4 mg/L, warrants more clinical studies.
PMID- 25139844
TI - Direct identification of bacteria from positive BacT/ALERT blood culture bottles
using matrix-assisted laser desorption ionization-time-of-flight mass
spectrometry.
AB - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry is a
fast and robust method for the identification of bacteria. In this study, we
evaluate the performance of a laboratory-developed lysis method (LDT) for the
rapid identification of bacteria from positive BacT/ALERT blood culture bottles.
Of the 168 positive bottles tested, 159 were monomicrobial, the majority of which
were Gram-positive organisms (61.0% versus 39.0%). Using a cut-off score of
>=1.7, 80.4% of the organisms were correctly identified to the species level, and
the identification rate of Gram-negative organisms (90.3%) was found to be
significantly greater than that of Gram-positive organisms (78.4%). The
simplicity and cost-effectiveness of the LDT enable it to be fully integrated
into the routine workflow of the clinical microbiology laboratory, allowing for
rapid identification of Gram-positive and Gram-negative bacteria within an hour
of blood culture positivity.
PMID- 25139845
TI - Structure and transfer of the vanA cluster in vanA-positive, vancomycin
susceptible Enterococcus faecium, and its revertant mutant.
AB - Of 18 vanA-positive vancomycin-susceptible Enterococcus faecium isolates, vanRS
in the vanA cluster was detected in all isolates, while vanHAX was detected in
only 2 isolates. Following exposure to glycopeptides, 22.2% of vancomycin
susceptible E. faecium (VSE) converted into vancomycin-resistant E. faecium. The
vanA cluster of the revertant mutant was transferred to the VSE isolates.
PMID- 25139846
TI - Familial systemic mastocytosis with germline KIT K509I mutation is sensitive to
treatment with imatinib, dasatinib and PKC412.
AB - Mastocytosis are myeloproliferative neoplasms commonly related to gain-of
function mutations involving the tyrosine kinase domain of KIT. We herein report
a case of familial systemic mastocytosis with the rare KIT K509I germ line
mutation affecting two family members: mother and daughter. In vitro treatment
with imatinib, dasatinib and PKC412 reduced cell viability of primary mast cells
harboring KIT K509I mutation. However, imatinib was more effective in inducing
apoptosis of neoplastic mast cells. Both patients with familial systemic
mastocytosis had remarkable hematological and skin improvement after three months
of imatinib treatment, suggesting that it may be an effective front line therapy
for patients harboring KIT K509I mutation.
PMID- 25139847
TI - Results of allogeneic stem cell transplantation in the Spanish MDS registry:
prognostic factors for low risk patients.
AB - Although new agents have been approved for the treatment of MDS, the only
curative approach is allogeneic hematopoietic stem cell transplantation (HSCT)
and thus, in particular circumstances this procedure has been proposed as a
treatment option for low risk patients. We have retrospectively analyzed the
results of HSCT in 291 patients from the Spanish MDS registry with special
attention to low risk MDS (LR-MDS) in order to define the variables that could
impact their clinical evolution after transplantation. At 2 years OS was 51% and
EFS was 50% (95% CI 0.7-4.5 years for OS and 95% CI 0.1-3.9 years for EFS). Among
43 LR-MDS, transplant-related mortality was 28%. At 3 years, OS was 67% (95% CI
264.7-8927.2 days for OS) and EFS was 64% (95% CI 0-9697.2 days for EFS). In the
multivariate analysis only cytogenetics retained statistical significant effect
on both OS (p=.047) and EFS (p=.046). Conditioning regimen could improve outcome
among this subset of patients (OS 86% and RFS 100% for patients receiving RIC
regimen). The present study confirms that specific disease characteristic as well
as transplant characteristics have a significant impact on transplant outcome.
Regarding low risk patients a non-myeloablative conditioning would be preferable
especially in cases without high-risk cytogenetics.
PMID- 25139848
TI - A paradigm for cybernetics, regulatory circuits and ultra-stability in cancer
biology and treatment.
PMID- 25139849
TI - Leveraging Administrative Data for Program Evaluations: A Method for Linking Data
Sets Without Unique Identifiers.
AB - In community-based wellness programs, Social Security Numbers (SSNs) are rarely
collected to encourage participation and protect participant privacy. One measure
of program effectiveness includes changes in health care utilization. For the 65
and over population, health care utilization is captured in Medicare
administrative claims data. Therefore, methods as described in this article for
linking participant information to administrative data are useful for program
evaluations where unique identifiers such as SSN are not available. Following
fuzzy matching methodologies, participant information from the National Study of
the Chronic Disease Self-Management Program was linked to Medicare administrative
data. Linking variables included participant name, date of birth, gender,
address, and ZIP code. Seventy-eight percent of participants were linked to their
Medicare claims data. Linking program participant information to Medicare
administrative data where unique identifiers are not available provides
researchers with the ability to leverage claims data to better understand program
effects.
PMID- 25139850
TI - Okadaic acid blocks the effects of 5-aza-2-deoxycytidine on consolidation,
acquisition and retrieval of morphine-induced place preference in rats.
AB - Recent studies indicated that epigenetic modification, especially DNA
methylation, play an important role in the persistence of addiction-related
memory. 5-aza-2-deoxycytidine (5-aza), an inhibitor of DNA methyltransferases,
was approved for clinical treatment. However, it is not clear whether 5-aza is
involved in opiate addiction. In this study, using the morphine-induced
conditioned place preference (mCPP) model in rats, we injected 5-aza into
hippocampus (CA1) and prelimbic cortex (PL), and tested the behavioral
consequences at various stages of consolidation, acquisition and retrieval.
Moreover, to test whether protein phosphatase regulates the effects of 5-aza,
protein phosphatase (PP) 1/2A inhibitor okadaic acid (OA) was infused before 5
aza injection. We found that 5-aza injection into CA1 but not into PL
significantly attenuated the consolidation and acquisition of mCPP, however, the
inhibition of DNA methylation in PL but not in CA1 enhanced the retrieval of
mCPP. All these behavioral effects were absent when OA was infused before 5-aza
injection. These findings suggest that 5-aza interfere opiate-related memory, and
protein phosphatase plays an important role in this process.
PMID- 25139851
TI - Semaphorin signalling during development.
AB - Semaphorins are secreted and membrane-associated proteins that regulate many
different developmental processes, including neural circuit assembly, bone
formation and angiogenesis. Trans and cis interactions between semaphorins and
their multimeric receptors trigger intracellular signal transduction networks
that regulate cytoskeletal dynamics and influence cell shape, differentiation,
motility and survival. Here and in the accompanying poster we provide an overview
of the molecular biology of semaphorin signalling within the context of specific
cell and developmental processes, highlighting the mechanisms that act to fine
tune, diversify and spatiotemporally control the effects of semaphorins.
PMID- 25139852
TI - Coordinating cell polarity: heading in the right direction?
AB - A diverse group of researchers working on both plant and animal systems met at a
Company of Biologists workshop to discuss 'Coordinating Cell Polarity'. The
meeting included considerable free discussion as well as presentations exploring
the ways that groups of cells in these various systems achieve coordinated cell
polarity. Here, we discuss commonalities, differences and themes that emerged
from these sessions that will serve to inform ongoing studies.
PMID- 25139853
TI - The cellular basis of tissue separation.
AB - The subdivision of the embryo into physically distinct regions is one of the most
fundamental processes in development. General hypotheses for tissue separation
based on differential adhesion or tension have been proposed in the past, but
with little experimental support. During the last decade, the field has
experienced a strong revival, largely driven by renewed interest in biophysical
modeling of development. Here, I will discuss the various models of boundary
formation and summarize recent studies that have shifted our understanding of the
process from the simple juxtaposition of global tissue properties to the
characterization of local cellular reactions. Current evidence favors a model
whereby separation is controlled by cell surface cues, which, upon cell-cell
contact, generate acute changes in cytoskeletal and adhesive properties to
inhibit cell mixing, and whereby the integration of multiple local cues may
dictate both the global morphogenetic properties of a tissue and its separation
from adjacent cell populations.
PMID- 25139854
TI - Runx1 is required for progression of CD41+ embryonic precursors into HSCs but not
prior to this.
AB - Haematopoiesis in adult animals is maintained by haematopoietic stem cells
(HSCs), which self-renew and can give rise to all blood cell lineages. The AGM
region is an important intra-embryonic site of HSC development and a wealth of
evidence indicates that HSCs emerge from the endothelium of the embryonic dorsal
aorta and extra-embryonic large arteries. This, however, is a stepwise process
that occurs through sequential upregulation of CD41 and CD45 followed by
emergence of fully functional definitive HSCs. Although largely dispensable at
later stages, the Runx1 transcription factor is crucially important during
developmental maturation of HSCs; however, exact points of crucial involvement of
Runx1 in this multi-step developmental maturation process remain unclear. Here,
we have investigated requirements for Runx1 using a conditional reversible
knockout strategy. We report that Runx1 deficiency does not preclude formation of
VE-cad+CD45-CD41+ cells, which are phenotypically equivalent to precursors of
definitive HSCs (pre-HSC Type I) but blocks transition to the subsequent CD45+
stage (pre-HSC Type II). These data emphasise that developmental progression of
HSCs during a very short period of time is regulated by precise stage-specific
molecular mechanisms.
PMID- 25139855
TI - Nuclear removal during terminal lens fiber cell differentiation requires CDK1
activity: appropriating mitosis-related nuclear disassembly.
AB - Lens epithelial cells and early lens fiber cells contain the typical complement
of intracellular organelles. However, as lens fiber cells mature they must
destroy their organelles, including nuclei, in a process that has remained
enigmatic for over a century, but which is crucial for the formation of the
organelle-free zone in the center of the lens that assures clarity and function
to transmit light. Nuclear degradation in lens fiber cells requires the nuclease
DNase IIbeta (DLAD) but the mechanism by which DLAD gains access to nuclear DNA
remains unknown. In eukaryotic cells, cyclin-dependent kinase 1 (CDK1), in
combination with either activator cyclins A or B, stimulates mitotic entry, in
part, by phosphorylating the nuclear lamin proteins leading to the disassembly of
the nuclear lamina and subsequent nuclear envelope breakdown. Although most post
mitotic cells lack CDK1 and cyclins, lens fiber cells maintain these proteins.
Here, we show that loss of CDK1 from the lens inhibited the phosphorylation of
nuclear lamins A and C, prevented the entry of DLAD into the nucleus, and
resulted in abnormal retention of nuclei. In the presence of CDK1, a single focus
of the phosphonuclear mitotic apparatus is observed, but it is not focused in
CDK1-deficient lenses. CDK1 deficiency inhibited mitosis, but did not prevent DNA
replication, resulting in an overall reduction of lens epithelial cells, with the
remaining cells possessing an abnormally large nucleus. These observations
suggest that CDK1-dependent phosphorylations required for the initiation of
nuclear membrane disassembly during mitosis are adapted for removal of nuclei
during fiber cell differentiation.
PMID- 25139856
TI - Heterotrimeric Go protein links Wnt-Frizzled signaling with ankyrins to regulate
the neuronal microtubule cytoskeleton.
AB - Drosophila neuromuscular junctions (NMJs) represent a powerful model system with
which to study glutamatergic synapse formation and remodeling. Several proteins
have been implicated in these processes, including components of canonical
Wingless (Drosophila Wnt1) signaling and the giant isoforms of the membrane
cytoskeleton linker Ankyrin 2, but possible interconnections and cooperation
between these proteins were unknown. Here, we demonstrate that the heterotrimeric
G protein Go functions as a transducer of Wingless-Frizzled 2 signaling in the
synapse. We identify Ankyrin 2 as a target of Go signaling required for NMJ
formation. Moreover, the Go-ankyrin interaction is conserved in the mammalian
neurite outgrowth pathway. Without ankyrins, a major switch in the Go-induced
neuronal cytoskeleton program is observed, from microtubule-dependent neurite
outgrowth to actin-dependent lamellopodial induction. These findings describe a
novel mechanism regulating the microtubule cytoskeleton in the nervous system.
Our work in Drosophila and mammalian cells suggests that this mechanism might be
generally applicable in nervous system development and function.
PMID- 25139857
TI - Systematic discovery of novel ciliary genes through functional genomics in the
zebrafish.
AB - Cilia are microtubule-based hair-like organelles that play many important roles
in development and physiology, and are implicated in a rapidly expanding spectrum
of human diseases, collectively termed ciliopathies. Primary ciliary dyskinesia
(PCD), one of the most prevalent of ciliopathies, arises from abnormalities in
the differentiation or motility of the motile cilia. Despite their biomedical
importance, a methodical functional screen for ciliary genes has not been carried
out in any vertebrate at the organismal level. We sought to systematically
discover novel motile cilia genes by identifying the genes induced by Foxj1, a
winged-helix transcription factor that has an evolutionarily conserved role as
the master regulator of motile cilia biogenesis. Unexpectedly, we find that the
majority of the Foxj1-induced genes have not been associated with cilia before.
To characterize these novel putative ciliary genes, we subjected 50 randomly
selected candidates to a systematic functional phenotypic screen in zebrafish
embryos. Remarkably, we find that over 60% are required for ciliary
differentiation or function, whereas 30% of the proteins encoded by these genes
localize to motile cilia. We also show that these genes regulate the proper
differentiation and beating of motile cilia. This collection of Foxj1-induced
genes will be invaluable for furthering our understanding of ciliary biology, and
in the identification of new mutations underlying ciliary disorders in humans.
PMID- 25139858
TI - Nephric duct insertion requires EphA4/EphA7 signaling from the pericloacal
mesenchyme.
AB - The vesico-ureteric junction (VUJ) forms through a complex developmental program
that connects the primordium of the upper urinary tract [the nephric duct (ND)]
with that of the lower urinary tract (the cloaca). The signals that orchestrate
the various tissue interactions in this program are poorly understood. Here, we
show that two members of the EphA subfamily of receptor tyrosine kinases, EphA4
and EphA7, are specifically expressed in the mesenchyme surrounding the caudal ND
and the cloaca, and that Epha4(-/-);Epha7(+/-) and Epha4(-/-);Epha7(-/-) (DKO)
mice display distal ureter malformations including ureterocele, blind and
ectopically ending ureters with associated hydroureter, megaureter and
hydronephrosis. We trace these defects to a late or absent fusion of the ND with
the cloaca. In DKO embryos, the ND extends normally and approaches the cloaca but
the tip subsequently looses its integrity. Expression of Gata3 and Lhx1 and their
downstream target Ret is severely reduced in the caudal ND. Conditional deletion
of ephrin B2 from the ND largely phenocopies these changes, suggesting that
EphA4/EphA7 from the pericloacal mesenchyme signal via ephrin B2 to mediate ND
insertion. Disturbed activity of this signaling module may entail defects of the
VUJ, which are frequent in the spectrum of congenital anomalies of the kidney and
the urinary tract (CAKUT) in human newborns.
PMID- 25139861
TI - Associations between active commuting, body fat, and body mass index: population
based, cross sectional study in the United Kingdom.
AB - OBJECTIVE: To determine if promotion of active modes of travel is an effective
strategy for obesity prevention by assessing whether active commuting (walking or
cycling for all or part of the journey to work) is independently associated with
objectively assessed biological markers of obesity. DESIGN: Cross sectional study
of data from the wave 2 Health Assessment subsample of Understanding Society, the
UK Household Longitudinal Study (UKHLS). The exposure of interest, commuting
mode, was self reported and categorised as three categories: private transport,
public transport, and active transport. PARTICIPANTS: The analytic samples (7534
for body mass index (BMI) analysis, 7424 for percentage body fat analysis) were
drawn from the representative subsample of wave 2 respondents of UKHLS who
provided health assessment data (n = 15,777). MAIN OUTCOME MEASURES: Body mass
index (weight (kg)/height (m)(2)); percentage body fat (measured by electrical
impedance). RESULTS: Results from multivariate linear regression analyses suggest
that, compared with using private transport, commuting by public or active
transport modes was significantly and independently predictive of lower BMI for
both men and women. In fully adjusted models, men who commuted via public or
active modes had BMI scores 1.10 (95% CI 0.53 to 1.67) and 0.97 (0.40 to 1.55)
points lower, respectively, than those who used private transport. Women who
commuted via public or active modes had BMI scores 0.72 (0.06 to 1.37) and 0.87
(0.36 to 0.87) points lower, respectively, than those using private transport.
Results for percentage body fat were similar in terms of magnitude, significance,
and direction of effects. CONCLUSIONS: Men and women who commuted to work by
active and public modes of transport had significantly lower BMI and percentage
body fat than their counterparts who used private transport. These associations
were not attenuated by adjustment for a range of hypothesised confounding
factors.
PMID- 25139862
TI - Isolated talonavicular fusion with tension band for Muller-Weiss syndrome.
AB - BACKGROUND: There are still controversies with regard to the operative treatment
in advanced Muller-Weiss syndrome (MWS), where the navicular undergoes avascular
necrosis and the talonavicular (TN) joint becomes arthritic. Most authors
advocate extended fusion, sacrificing hindfoot mobility. To restore TN alignment
and to achieve stable fixation, we developed a new isolated TN fusion technique
applying the principles of a static tension band. The aim of the present study
was to report the midterm results of a preliminary series of patients and their
clinical and radiographic outcomes. METHODS: Ten feet (10 patients; 8 females, 2
males; age 63 +/- 16.7 [range, 34-83] years) with advanced deformity of MWS (3
Maceira's stage III and 7 stage IV) were treated with isolated TN arthrodesis
using the tension band technique. The American Orthopaedic Foot and Ankle Society
(AOFAS) ankle-hindfoot score was used to evaluate the functional outcome.
Standard angles were measured to determine the amount of correction achieved
through the operative treatment. The minimum follow-up was 24 (range, 24-43)
months. RESULTS: Trabeculation was seen to cross the fusion site on radiographs
in 8 patients after 2 and in 1 patient after 3 months. One case needed revision
after 13 months due to implant failure; after additional screw fixation, bony
healing was achieved 2 months later. At last follow-up, all cases described a
high level of satisfaction. Postoperatively, the AOFAS score improved from 33
(range, 18-48) to 88.3 (range, 79-100) (P < .0001) points, the AP talocalcaneal
angle increased from 14.2 (range, 1-22) to 22.7 (range, 12-30) degrees (P =
.0007), and the calcaneal pitch increased from 10.3 (range, 3-22) to 14.7 (range,
8-22) degrees (P = .0006). CONCLUSION: The static tension band technique is a
new, promising technique to treat MWS patients, providing stability against the
counteracting deforming forces. Therefore, we consider this technique as our
treatment of choice in patients with stage III and stage IV MWS. LEVEL OF
EVIDENCE: Level IV, prospective case series.
PMID- 25139863
TI - Gestalt grouping via closure degrades suprathreshold depth percepts.
AB - It is well known that the perception of depth is susceptible to changes in
configuration. For example, stereoscopic precision for a pair of vertical lines
can be dramatically reduced when these lines are connected to form a closed
object. Here, we extend this paradigm to suprathreshold estimates of perceived
depth. Using a touch-sensor, observers made quantitative estimates of depth
between a vertical line pair presented in isolation or as edges of a closed
rectangular object with different figural interpretations. First, we show that
the amount of depth estimated within a closed rectangular object is consistently
reduced relative to the vertical edges presented in isolation or when they form
the edges of two segmented objects. We then demonstrate that the reduction in
perceived depth for closed objects is modulated by manipulations that influence
perceived closure of the central figure. Depth percepts were most disrupted when
the horizontal connectors and vertical lines matched in color. Perceived depth
increased slightly when the connectors had opposite contrast polarity, but
increased dramatically when flankers were added. Thus, as grouping cues were
added to counter the interpretation of a closed object, the depth degradation
effect was systematically eliminated. The configurations tested here rule out
explanations based on early, local interactions such as inhibition or cue
conflict; instead, our results provide strong evidence of the impact of Gestalt
grouping, via closure, on depth magnitude percepts from stereopsis.
PMID- 25139864
TI - Human vision is attuned to the diffuseness of natural light.
AB - All images are highly ambiguous, and to perceive 3-D scenes, the human visual
system relies on assumptions about what lighting conditions are most probable.
Here we show that human observers' assumptions about lighting diffuseness are
well matched to the diffuseness of lighting in real-world scenes. We use a novel
multidirectional photometer to measure lighting in hundreds of environments, and
we find that the diffuseness of natural lighting falls in the same range as
previous psychophysical estimates of the visual system's assumptions about
diffuseness. We also find that natural lighting is typically directional enough
to override human observers' assumption that light comes from above. Furthermore,
we find that, although human performance on some tasks is worse in diffuse light,
this can be largely accounted for by intrinsic task difficulty. These findings
suggest that human vision is attuned to the diffuseness levels of natural
lighting conditions.
PMID- 25139868
TI - Healthier commuting.
PMID- 25139869
TI - Universal cures for idiosyncratic illnesses: A genealogy of therapeutic reasoning
in the mental health field.
AB - Over the past decades, there has been a significant increase in prescriptions of
psychotropic drugs for mental disorders. So far, most of the explanations of the
phenomenon have focused on the process of medicalization, but little attention
has been cast towards physicians' day-to-day clinical reasoning, and the way it
affects therapeutic decision-making. This article addresses the complex
relationship between aetiology, diagnosis and drug treatment by examining the
style of reasoning underlying prescribing practices through an historical lens. A
genealogy of contemporary prescribing practices is proposed, that draws
significant comparisons between 19th-century medicine and modern psychiatry.
Tensions between specific, standardized cures and specific, idiosyncratic
patients have been historically at play in clinical reasoning - and still are
today. This inquiry into the epistemological foundations of contemporary drug
prescription reveals an underlying search for scientific legitimacy.
PMID- 25139870
TI - Education as networking: Rethinking the success of the harm reduction policy of
Taiwan.
AB - The harm reduction policy of Taiwan has been considered a success. However, the
HIV incidence among injection drug users declined before the nationwide needle
and syringe program and drug substitution treatments were implemented. Thus,
other factors in the policy might have contributed to its success. Some authors
have suggested that education may have played a pivotal part. In this research,
the purported significance of education in the success of the policy is
conceptualized by reviewing the studies on harm reduction in Taiwan and
reflecting upon my own fieldwork. Moreover, relevant literature is used as
reference to reformulate this notion of education. This article shows that harm
reduction education may be conducted in numerous forms, most of which are non
formal, improvisational, and contingent. Non-governmental organizations may play
a role, but more actors, strategies, infrastructures, and interactions should be
considered. This article draws from actor-network theory and refines the current
thesis that attributes the policy success to education by utilizing three
reflections, namely, appreciating materiality and spatiality, recognizing covert
actors in the networking, and treating education as an outcome rather than a
means. In conclusion, looking at education as a form of networking offers
theoretical insight that increases understanding of its participants, mechanisms,
processes, and permutations.
PMID- 25139871
TI - Facile fabrication of a well-ordered porous Cu-doped SnO2 thin film for H2S
sensing.
AB - Well-ordered Cu-doped and undoped SnO2 porous thin films with large specific
surface areas have been fabricated on a desired substrate using a self-assembled
soft template combined with simple physical cosputtering deposition. The Cu-doped
SnO2 porous film gas sensor shows a significant enhancement in its sensing
performance, including a high sensitivity, selectivity, and a fast response and
recovery time. The sensitivity of the Cu-doped SnO2 porous sensor is 1 order of
magnitude higher than that of the undoped SnO2 sensor, with average response and
recovery times to 100 ppm of H2S of ~ 10.1 and ~ 42.4 s, respectively, at the
optimal operating temperature of 180 degrees C. The well-defined porous sensors
fabricated by the method also exhibit high reproducibility because of the
accurately controlled fabrication process. The facile process can be easily
extended to the fabrication of other semiconductor oxide gas sensors with easy
doping and multilayer porous nanostructure for practical sensing applications.
PMID- 25139872
TI - Integrating community health workers into a patient-centered medical home to
support disease self-management among Vietnamese Americans: lessons learned.
AB - There is evidence that patient-centered medical homes (PCMHs) and community
health workers (CHWs) improve chronic disease management. There are few models
for integrating CHWs into PCMHs in order to enhance disease self-management
support among diverse populations. In this article, we describe how a community
based nonprofit agency, a PCMH, and academic partners collaborated to develop and
implement the Patient Resource and Education Program (PREP). We employed CHWs as
PCMH care team members to provide health education and support to Vietnamese
American patients with uncontrolled diabetes and/or hypertension. We began by
conducting focus groups to assess patient knowledge, desire for support, and
availability of community resources. Based on findings, we developed PREP with
CHW guidance on cultural tailoring of educational materials and methods. CHWs
received training in core competencies related to self-management support
principles and conducted the 4-month intervention for PCMH patients. Throughout
the program, we conducted process evaluation through structured team meetings and
patient satisfaction surveys. We describe successes and challenges associated
with PREP delivery including patient recruitment, structuring/documenting visits,
and establishing effective care team integration, work flow, and communication.
Strategies for mitigating these issues are presented, and we make recommendations
for other PCMHs seeking to integrate CHWs into care teams.
PMID- 25139873
TI - Early deterioration after thrombolysis plus aspirin in acute stroke: a post hoc
analysis of the Antiplatelet Therapy in Combination with Recombinant t-PA
Thrombolysis in Ischemic Stroke trial.
AB - BACKGROUND AND PURPOSE: Aspirin early after intravenous thrombolysis in acute
ischemic stroke increases the risk of symptomatic intracranial hemorrhage (SICH),
without influencing functional outcome at 3 months. The effect of aspirin on
early neurological deterioration (END) was explored as a post hoc analysis of the
randomized Antiplatelet Therapy in Combination With Recombinant t-PA Thrombolysis
in Ischemic Stroke (ARTIS) trial. METHODS: END, defined as a >=4 points National
Institutes of Health Stroke Scale worsening <=24 hours after intravenous
thrombolysis, was categorized into SICH (ENDSICH) and cerebral ischemia (ENDCI).
Multinomial logistic regression was used to assess the effect of aspirin on END.
RESULTS: Of the 640 patients, 31 patients (4.8%) experienced END (14 ENDSICH, 17
ENDCI). Aspirin increased the risk of ENDSICH (odds ratio, 3.73; 95% confidence
interval, 1.03-13.49) but not of ENDCI (odds ratio, 1.14; 95% confidence
interval, 0.44-3.00). After adjustment for other explanatory variables, the
association between aspirin and ENDSICH remained significant. CONCLUSIONS: In
this trial, there is no evidence of an early antithrombotic effect from the
addition of aspirin to intravenous thrombolysis in acute ischemic stroke.
PMID- 25139874
TI - Association of interleukin-6 with the progression of carotid atherosclerosis: a 9
year follow-up study.
AB - BACKGROUND AND PURPOSE: Limited information is available on the long-term effects
of interleukin-6 (IL-6) on systemic atherosclerosis. The purpose of the present
study was to clarify the relationship between chronic elevation of IL-6 and the
long-term progression of carotid atherosclerosis. METHODS: We prospectively
evaluated 210 patients with >=1 vascular risk factors for 9.0+/-1.0 years.
Carotid mean-maximal intima-media thickness (mmIMT), the serum high-sensitivity C
reactive protein (hs-CRP) level, and the serum IL-6 level were measured at
baseline and every 3 years. The associations between the progression of mmIMT and
the long-term average levels of hs-CRP and IL-6 were analyzed. RESULTS: Carotid
mmIMT increased throughout the study period (0.031+/-0.026 mm/y). Baseline mmIMT
was significantly associated with baseline hs-CRP (P=0.002) and baseline IL-6
(P<0.001) levels. Progression of mmIMT was positively correlated with average hs
CRP (P=0.001) and average IL-6 (P<0.001) levels. When adjusted for age, sex,
traditional risk factors, and baseline mmIMT, mmIMT progression remained
significantly associated only with the average IL-6 level (standardized
beta=0.17; P=0.02), but not with the average hs-CRP level (standardized
beta=0.10; P=0.18). CONCLUSIONS: Chronic elevation of serum IL-6 was associated
with the progression of atherosclerosis in patients with vascular risk factors.
IL-6 could be used as a quantitative marker and a potential therapeutic target
for accelerated atherosclerosis.
PMID- 25139875
TI - Intervention of death-associated protein kinase 1-p53 interaction exerts the
therapeutic effects against stroke.
AB - BACKGROUND AND PURPOSE: Death-associated protein kinase 1 (DAPK1) interacts with
the tumor suppressor gene p53 via a direct binding of a death domain of DAPK1 to
a DNA-binding motif (DM) of p53 (p53DM) and converges multiple cell death
pathways in stroke. The goals of this study are to determine whether disruption
of DAPK1-p53 interaction is therapeutically effective against stroke. METHODS: We
synthesized a membrane-permeable p53DM peptide (Tat-p53DM) and tested the
therapeutic effects of Tat-p53DM in a mouse model with stroke. RESULTS: We showed
that Tat-p53DM blocked DAPK1-p53 interaction in brain cells in vivo. When
administered 6 hours after stroke onset in adult male mice, Tat-p53DM was still
therapeutically effective against brain damages and improved neurological
functions. CONCLUSIONS: DAPK1-p53 interaction is a preferred target for
therapeutic intervention of stroke.
PMID- 25139876
TI - Follistatin-like 1 attenuates apoptosis via disco-interacting protein 2 homolog
A/Akt pathway after middle cerebral artery occlusion in rats.
AB - BACKGROUND AND PURPOSE: Follistatin-like 1 (FSTL1), an extracellular
glycoprotein, has been reported to decrease apoptosis in ischemic cardiac
diseases, but its effect in ischemic stroke has not been examined. We
hypothesized that recombinant FSTL1 attenuates neuronal apoptosis through its
receptor disco-interacting protein 2 homolog A (DIP2A) and the Akt pathway after
middle cerebral artery occlusion (MCAO) in rats. METHODS: One hundred forty male
Sprague-Dawley rats were subjected to 2 hours of MCAO followed by reperfusion. In
a subset of animals, the time course and location of FSTL1 and DIP2A were
detected by Western blot and immunofluorescence double staining. Another set of
animals were intracerebroventricularly given either recombinant FSTL1 1 hour
after reperfusion or FSTL1-small interfering RNA (siRNA) 48 hours before
reperfusion. Additionally, DIP2A was knockdown by siRNA in some animals.
Infarction volume and neurological deficits were measured, and the expression of
FSTL1, DIP2A, phosphorylated Akt, cleaved caspase-3, and terminal
deoxynucleotidyl transferase dUTP nick end labeling were quantified using Western
blot. RESULTS: The expression of FSTL1 and DIP2A was increased in neurons and
peaked 24 hours after MCAO. Recombinant FSTL1 reduced brain infarction and
improved neurological deficits 24 and 72 hours after MCAO via activation of its
receptor DIP2A and downstream phosphorylation of Akt. These effects were reversed
by DIP2A-siRNA and FSTL1-siRNA. CONCLUSIONS: Recombinant FSTL1 decreases neuronal
apoptosis and improves neurological deficits through phosphorylation of Akt by
activation of its receptor DIP2A after MCAO in rats. Thus, FSTL1 may have
potentials as a treatment for patients with ischemic stroke.
PMID- 25139877
TI - Impact of living alone on the care and outcomes of patients with acute stroke.
AB - BACKGROUND AND PURPOSE: Outcomes among patients living alone at stroke onset
could be directly affected by reduced access to acute therapies or indirectly
through the effects of social isolation. We examined the associations between
living alone at home and acute stroke care and outcomes in the Registry of the
Canadian Stroke Network. METHODS: Between 2003 and 2008, 10 048 patients with
acute stroke (87% ischemic, 13% hemorrhagic) who were living at home were
admitted to 11 Ontario hospitals. Outcomes included arrival<=2.5 hours of onset,
thrombolytic treatment, discharge home, 30-day and 1-year mortality, and 1-year
readmission. The effects of living alone versus living with others were
determined using multivariable logistic regression. RESULTS: Overall, 22.8%
(n=2288) of patients were living alone at home before stroke. Subjects living
alone were significantly older (mean, 74.6 versus 71.5 years), more likely to be
women (61.5% versus 41.4%), widowed (53.7% versus 12.3%), or single (21.5% versus
3.8%). Patients living alone were less likely to arrive within 2.5 hours (28.3%
versus 40.0%; adjusted odds ratio, 0.54; 95% confidence interval, 0.48-0.60), to
receive thrombolysis (8.0% versus 14.0%; adjusted odds ratio, 0.52; 95%
confidence interval, 0.43-0.63), or to be discharged home (46.0% versus 54.7%;
adjusted odds ratio, 0.65; 95% confidence interval, 0.58-0.73). There were no
significant associations between living alone and mortality or readmission.
CONCLUSIONS: Patients living alone had delayed hospital arrival, less
thrombolytic therapy, and were less likely to return home. Greater understanding
of the inter-relationships among living alone, social isolation, access to stroke
care, and outcomes is needed.
PMID- 25139878
TI - Social network, social support, and risk of incident stroke: Atherosclerosis Risk
in Communities study.
AB - BACKGROUND AND PURPOSE: Having a small social network and lack of social support
have been associated with incident coronary heart disease; however,
epidemiological evidence for incident stroke is limited. We assessed the
longitudinal association of a small social network and lack of social support
with risk of incident stroke and evaluated whether the association was partly
mediated by vital exhaustion and inflammation. METHODS: The Atherosclerosis Risk
in Communities study measured social network and social support in 13 686 men and
women (mean, 57 years; 56% women; 24% black; 76% white) without a history of
stroke. Social network was assessed by the 10-item Lubben Social Network Scale
and social support by a 16-item Interpersonal Support Evaluation List-Short Form.
RESULTS: During a median follow-up of 18.6 years, 905 incident strokes occurred.
Relative to participants with a large social network, those with a small social
network had a higher risk of stroke (hazard ratio [95% confidence interval], 1.44
[1.02-2.04]) after adjustment for demographics, socioeconomic variables, marital
status, behavioral risk factors, and major stroke risk factors. Vital exhaustion,
but not inflammation, partly mediated the association between a small social
network and incident stroke. Social support was unrelated to incident stroke.
CONCLUSIONS: In this sample of US community-dwelling men and women, having a
small social network was associated with excess risk of incident stroke. As with
other cardiovascular conditions, having a small social network may be associated
with a modestly increased risk of incident stroke.
PMID- 25139880
TI - A randomized trial of unruptured brain arteriovenous malformations trial: an
editorial review.
PMID- 25139879
TI - Sickle cell trait and incident ischemic stroke in the Atherosclerosis Risk in
Communities study.
AB - BACKGROUND AND PURPOSE: Numerous case reports describe stroke in individuals with
sickle cell trait (SCT) in the absence of traditional risk factors for
cerebrovascular disease. To date, no prospective epidemiological studies have
investigated this association. METHODS: A population-based sample of blacks
(n=3497; mean age=54 years; female=62%) was followed from 1987 to 2011 in the
Atherosclerosis Risk in Communities (ARIC) study, contributing a total of 65 371
person-years. Hazard ratios and incidence rate differences for ischemic stroke
were estimated, contrasting SCT to homozygous hemoglobin A. Models were adjusted
for age, sex, smoking, diabetes mellitus, hypertension, total cholesterol, atrial
fibrillation, and coronary heart disease. RESULTS: SCT was identified in 223
(6.4%) participants. During a median follow-up of 22 years, 401 subjects
experienced incident stroke (89% ischemic). Incident ischemic stroke was more
frequent among those with SCT (13%) than those with homozygous hemoglobin A
(10%). SCT was associated with an ischemic stroke hazard ratio of 1.4 (1.0-2.0)
and an incidence rate difference amounting to 1.9 (0.4-3.8) extra strokes per
1000 person-years. CONCLUSIONS: We observed an increased risk of ischemic stroke
in blacks with SCT. Further investigation of the incidence and pathophysiology of
stroke in patients with SCT is warranted.
PMID- 25139881
TI - Social network and stroke risk: size matters.
PMID- 25139882
TI - Quantification of the glycemic response to microdoses of subcutaneous glucagon at
varying insulin levels.
AB - OBJECTIVE: Glucagon delivery in closed-loop control of type 1 diabetes is
effective in minimizing hypoglycemia. However, high insulin concentration lowers
the hyperglycemic effect of glucagon, and small doses of glucagon in this setting
are ineffective. There are no studies clearly defining the relationship between
insulin levels, subcutaneous glucagon, and blood glucose. RESEARCH DESIGN AND
METHODS: Using a euglycemic clamp technique in 11 subjects with type 1 diabetes,
we examined endogenous glucose production (EGP) of glucagon (25, 75, 125, and 175
MUg) at three insulin infusion rates (0.016, 0.032, and 0.05 units/kg/h) in a
randomized, crossover study. Infused 6,6-dideuterated glucose was measured every
10 min, and EGP was determined using a validated glucoregulatory model. Area
under the curve (AUC) for glucose production was the primary outcome, estimated
over 60 min. RESULTS: At low insulin levels, EGP rose proportionately with
glucagon dose, from 5 +/- 68 to 112 +/- 152 mg/kg (P = 0.038 linear trend),
whereas at high levels, there was no increase in glucose output (19 +/- 53 to 26
+/- 38 mg/kg, P = NS). Peak glucagon serum levels and AUC correlated well with
dose (r2 = 0.63, P < 0.001), as did insulin levels with insulin infusion rates
(r2 = 0.59, P < 0.001). CONCLUSIONS: EGP increases steeply with glucagon doses
between 25 and 175 MUg at lower insulin infusion rates. However, high insulin
infusion rates prevent these doses of glucagon from significantly increasing
glucose output and may reduce glucagon effectiveness in preventing hypoglycemia
when used in the artificial pancreas.
PMID- 25139883
TI - Leptin is associated with exaggerated brain reward and emotion responses to food
images in adolescent obesity.
AB - OBJECTIVE: In the U.S., an astonishing 12.5 million children and adolescents are
now obese, predisposing 17% of our nation's youth to metabolic complications of
obesity, such as type 2 diabetes (T2D). Adolescent obesity has tripled over the
last three decades in the setting of food advertising directed at children. Obese
adults exhibit increased brain responses to food images in motivation-reward
pathways. These neural alterations may be attributed to obesity-related metabolic
changes, which promote food craving and high-calorie food (HCF) consumption. It
is not known whether these metabolic changes affect neural responses in the
adolescent brain during a crucial period for establishing healthy eating
behaviors. RESEARCH DESIGN AND METHODS: Twenty-five obese (BMI 34.4 kg/m2, age
15.7 years) and fifteen lean (BMI 20.96 kg/m2, age 15.5 years) adolescents
underwent functional MRI during exposure to HCF, low-calorie food (LCF), and
nonfood (NF) visual stimuli 2 h after isocaloric meal consumption. RESULTS: Brain
responses to HCF relative to NF cues increased in obese versus lean adolescents
in striatal-limbic regions (i.e., putamen/caudate, insula, amygdala) (P < 0.05,
family-wise error [FWE]), involved in motivation-reward and emotion processing.
Higher endogenous leptin levels correlated with increased neural activation to
HCF images in all subjects (P < 0.05, FWE). CONCLUSIONS: This significant
association between higher circulating leptin and hyperresponsiveness of brain
motivation-reward regions to HCF images suggests that dysfunctional leptin
signaling may contribute to the risk of overconsumption of these foods, thus
further predisposing adolescents to the development of obesity and T2D.
PMID- 25139884
TI - Increased serum calcium levels and risk of type 2 diabetes in individuals at high
cardiovascular risk.
AB - OBJECTIVE: Insulin resistance and secretion depend on calcium homeostasis. Cross
sectional studies have associated elevated serum calcium levels with markers of
impaired glucose metabolism. However, only one prospective cohort study has
demonstrated an increased risk of diabetes in individuals with increased serum
calcium concentrations. The aim of the current study was to prospectively
investigate the association between albumin-adjusted serum calcium concentrations
and type 2 diabetes in subjects at high cardiovascular risk. RESEARCH DESIGN AND
METHODS: Prospective assessment of participants from two Spanish PREDIMED study
centers where serum calcium levels were measured at baseline and yearly during
follow-up. Multivariate-adjusted Cox regression models were fitted to assess
associations between baseline and changes during follow-up in serum calcium
levels and relative risk of diabetes incidence. RESULTS: After a median follow-up
of 4.78 years, 77 new cases of type 2 diabetes occurred. An increase in serum
calcium levels during follow-up was related to an increased risk of diabetes. In
comparison with individuals in the lowest tertile (-0.78 +/- 0.29 mg/dL), the
hazard ratio (HR) and 95% CI for diabetes incidence in individuals in the higher
tertile of change (0.52 +/- 0.13 mg/dL) during follow-up was 3.48 (95% CI 1.48
8.17; P for trend = 0.01). When albumin-adjusted serum calcium was analyzed as a
continuous variable, per 1 mg/dL increase, the HR of diabetes incidence was 2.87
(95% CI 1.18-6.96; P value = 0.02). These associations remained significant after
individuals taking calcium supplements or having calcium levels out of normal
range had been excluded. CONCLUSIONS: An increase in serum calcium concentrations
is associated with an increased risk of type 2 diabetes in individuals at high
cardiovascular risk.
PMID- 25139885
TI - Adjusting glucose-stimulated insulin secretion for adipose insulin resistance: an
index of beta-cell function in obese adults.
AB - OBJECTIVE: The hyperbolic relationship between insulin secretion and sensitivity
has been used to assess in vivo beta-cell function (i.e., the disposition index).
The disposition index emphasizes the importance of taking into account both
skeletal muscle and hepatic insulin resistance to depict insulin secretion.
However, we propose that adipose tissue insulin resistance also needs to be
accounted for when characterizing glucose-stimulated insulin secretion (GSIS)
because elevated plasma free fatty acids (FFAs) impair beta-cell function.
RESEARCH DESIGN AND METHODS: To characterize the adipose disposition index, we
used [1-(14)C] palmitate infusion to determine basal FFA turnover rate/adipose
insulin resistance and an oral glucose tolerance test to characterize the first
(i.e., 0-30 min) and second phase (i.e., 60-120 min) of GSIS. We validated a
simplified version of the tracer infusion calculation as the product of (1/plasma
FFA concentration * plasma insulin concentration) * GSIS in 44 obese insulin
resistant subjects. RESULTS: The plasma FFA and palmitate tracer infusion
calculations of the first- and second-phase disposition index were strongly
correlated (r = 0.86, P < 0.000001 and r = 0.89, P < 0.000001, respectively). The
first- and second-phase adipose disposition index derived from plasma FFA also
was tightly associated with fasting hyperglycemia (r = -0.87, P < 0.00001 and r =
-0.89, P < 0.00001, respectively) and 2-h glucose concentrations (r = -0.86, P <
0.00001 and r = -0.90, P < 0.00001). CONCLUSIONS: Adjusting GSIS for adipose
insulin resistance provides an index of beta-cell function in obese subjects
across the glucose spectrum. Plasma FFA-derived calculations of beta-cell
function may provide additional insight into the role of adipose tissue in
glucose regulation.
PMID- 25139886
TI - Diabetes risk among overweight and obese metabolically healthy young adults.
AB - OBJECTIVE: To determine diabetes incidence over time among obese young adults
without metabolic risk factors. RESEARCH DESIGN AND METHODS: Incident diabetes
during a median follow-up of 6.1 years was assessed among 33,939 young men (mean
age 30.9 +/- 5.2 years) of the Metabolic, Lifestyle and Nutrition Assessment in
Young Adults cohort who were stratified for BMI and the number of metabolic
abnormalities (based on the Adult Treatment Panel-III). Metabolically healthy
(MH) obesity was defined as BMI >=30 kg/m2 in the presence of normoglycemia,
normal blood pressure, and normal levels of fasting triglyceride and HDL
cholesterol levels (n = 631). RESULTS: A total of 734 new cases of diabetes were
diagnosed during 210,282 person-years of follow-up. The incidence rate of
diabetes among participants with no metabolic risk factors was 1.15, 2.10, and
4.34 cases per 1,000 person-years among lean, overweight, and obese participants,
respectively. In a multivariable model adjusted for age, region of origin, family
history of diabetes, physical activity, fasting plasma glucose, triglyceride
level, HDL-cholesterol, systolic blood pressure, and white blood cell count, a
higher diabetes risk was observed among MH-overweight (hazard ratio [HR] 1.89
[95% CI 1.25-2.86]; P < 0.001) and MH-obese (HR 3.88 [95% CI 1.94-7.77]; P <
0.001) compared with MH-normal weight subjects. There was no interaction between
BMI and the number of metabolic abnormalities at enrollment in predicting
diabetes risk. CONCLUSIONS: Healthy metabolic profile and the absence of diabetes
risk factors do not protect young adults from incident diabetes associated with
overweight and obesity.
PMID- 25139887
TI - Serco plans to pull out of clinical service provision in the UK.
PMID- 25139888
TI - Reconciling hierarchical taxonomy with molecular phylogenies.
PMID- 25139889
TI - Predictive values of GPs' suspicion of serious disease are high enough to warrant
subsequent investigation.
PMID- 25139890
TI - Human papillomavirus (HPV) is not an equitable virus.
PMID- 25139891
TI - Genitourinary medicine clinics may not see young men who have sex with men before
they become infected with human papillomavirus (HPV).
PMID- 25139892
TI - Effects of lifetime stress exposure on mental and physical health in young
adulthood: How stress degrades and forgiveness protects health.
AB - To examine risk and resilience factors that affect health, lifetime stress
exposure histories, dispositional forgiveness levels, and mental and physical
health were assessed in 148 young adults. Greater lifetime stress severity and
lower levels of forgiveness each uniquely predicted worse mental and physical
health. Analyses also revealed a graded Stress * Forgiveness interaction effect,
wherein associations between stress and mental health were weaker for persons
exhibiting more forgiveness. These data are the first to elucidate the
interactive effects of cumulative stress severity and forgiveness on health, and
suggest that developing a more forgiving coping style may help minimize stress
related disorders.
PMID- 25139893
TI - Attention deficit hyperactivity disorder symptomatology and pediatric obesity:
Psychopathology or sleep deprivation?
AB - The relationship between attention deficit hyperactivity disorder (ADHD) and
obesity in children has received considerable attention in recent years. However,
the literature currently overlooks the potential causal and maintaining role that
sleep problems may play in this relationship. Using a biopsychosocial framework,
this article highlights how sleep problems impact the biological, psychological,
and social aspects of both ADHD symptomatology and obesity. An in-depth
examination of this model illustrates the imperative need for future research and
clinical practice to recognize and explore the role sleep has in the link between
obesity and ADHD symptomatology.
PMID- 25139894
TI - Relationship between infertility-related stress and emotional distress and
marital satisfaction.
AB - The aim of this study was to evaluate the predictive effects of infertility
related stress on psychological distress and marital satisfaction. Structural
equation modeling was used to estimate a nonrecursive model hypothesizing the
impact of infertility-related stress on both emotional distress and marital
dissatisfaction, which were supposed to have a reciprocal influence on each
other. The model was estimated using data from a sample of 150 infertile patients
(78 males and 72 females). Findings confirmed the predictive effects of
infertility-related stress on both emotional and marital distress. However,
infertility-related stress was found to have more impact on emotional distress
than on marital satisfaction.
PMID- 25139895
TI - Psychological resilience moderates the impact of social support on loneliness of
"left-behind" children.
AB - This study examined the moderator effect of psychological resilience on the
relationship between social support and loneliness of the "left-behind" children.
A total of 200 left-behind girls and 214 left-behind boys completed the measures
of psychological resilience, social support, and loneliness. Hierarchical
regression analysis showed that psychological resilience moderated the
association between social support and loneliness. When left-behind children
reported a low level of psychological resilience, those with high social support
reported lower scores in loneliness than those with low social support. However,
the impact of social support on loneliness was much smaller in the high
psychological resilience group, compared with that in low psychological
resilience group.
PMID- 25139896
TI - Cardiovascular disease in Europe 2014: epidemiological update.
AB - This paper provides an update for 2014 on the burden of cardiovascular disease
(CVD), and in particular coronary heart disease (CHD) and stroke, across the
countries of Europe. Cardiovascular disease causes more deaths among Europeans
than any other condition, and in many countries still causes more than twice as
many deaths as cancer. There is clear evidence in most countries with available
data that mortality and case-fatality rates from CHD and stroke have decreased
substantially over the last 5-10 years but at differing rates. The differing
recent trends have therefore led to increasing inequalities in the burden of CVD
between countries. For some Eastern European countries, including Russia and
Ukraine, the mortality rate for CHD for 55-60 year olds is greater than the
equivalent rate in France for people 20 years older.
PMID- 25139897
TI - Reanalysis or redefinition of the hypothesis?
PMID- 25139898
TI - A rare coronary anomaly: origin of the right coronary artery from the left
ventricular outflow tract.
PMID- 25139899
TI - Biofilms formed by gram-negative bacteria undergo increased lipid a
palmitoylation, enhancing in vivo survival.
AB - Bacterial biofilm communities are associated with profound physiological changes
that lead to novel properties compared to the properties of individual
(planktonic) bacteria. The study of biofilm-associated phenotypes is an essential
step toward control of deleterious effects of pathogenic biofilms. Here we
investigated lipopolysaccharide (LPS) structural modifications in Escherichia
coli biofilm bacteria, and we showed that all tested commensal and pathogenic E.
coli biofilm bacteria display LPS modifications corresponding to an increased
level of incorporation of palmitate acyl chain (palmitoylation) into lipid A
compared to planktonic bacteria. Genetic analysis showed that lipid A
palmitoylation in biofilms is mediated by the PagP enzyme, which is regulated by
the histone-like protein repressor H-NS and the SlyA regulator. While lipid A
palmitoylation does not influence bacterial adhesion, it weakens inflammatory
response and enhances resistance to some antimicrobial peptides. Moreover, we
showed that lipid A palmitoylation increases in vivo survival of biofilm bacteria
in a clinically relevant model of catheter infection, potentially contributing to
biofilm tolerance to host immune defenses. The widespread occurrence of increased
lipid A palmitoylation in biofilms formed by all tested bacteria suggests that it
constitutes a new biofilm-associated phenotype in Gram-negative bacteria.
IMPORTANCE: Bacterial communities called biofilms display characteristic
properties compared to isolated (planktonic) bacteria, suggesting that some
molecules could be more particularly produced under biofilm conditions. We
investigated biofilm-associated modifications occurring in the lipopolysaccharide
(LPS), a major component of all Gram-negative bacterial outer membrane. We showed
that all tested commensal and pathogenic biofilm bacteria display high
incorporation of a palmitate acyl chain into the lipid A part of LPS. This lipid
A palmitoylation is mediated by the PagP enzyme, whose expression in biofilm is
controlled by the regulatory proteins H-NS and SlyA. We also showed that lipid A
palmitoylation in biofilm bacteria reduces host inflammatory response and
enhances their survival in an animal model of biofilm infections. While these
results provide new insights into the biofilm lifestyle, they also suggest that
the level of lipid A palmitoylation could be used as an indicator to monitor the
development of biofilm infections on medical surfaces.
PMID- 25139900
TI - Mycobacterium tuberculosis alters the metalloprotease activity of the COP9
signalosome.
AB - Inhibition of apoptotic death of macrophages by Mycobacterium tuberculosis
represents an important mechanism of virulence that results in pathogen survival
both in vitro and in vivo. To identify M. tuberculosis virulence determinants
involved in the modulation of apoptosis, we previously screened a transposon bank
of mutants in human macrophages, and an M. tuberculosis clone with a
nonfunctional Rv3354 gene was identified as incompetent to suppress apoptosis.
Here, we show that the Rv3354 gene encodes a protein kinase that is secreted
within mononuclear phagocytic cells and is required for M. tuberculosis
virulence. The Rv3354 effector targets the metalloprotease (JAMM) domain within
subunit 5 of the COP9 signalosome (CSN5), resulting in suppression of apoptosis
and in the destabilization of CSN function and regulatory cullin-RING ubiquitin
E3 enzymatic activity. Our observation suggests that alteration of the
metalloprotease activity of CSN by Rv3354 possibly prevents the ubiquitin
dependent proteolysis of M. tuberculosis-secreted proteins. IMPORTANCE :
Macrophage protein degradation is regulated by a protein complex called a
signalosome. One of the signalosomes associated with activation of ubiquitin and
protein labeling for degradation was found to interact with a secreted protein
from M. tuberculosis, which binds to the complex and inactivates it. The
interference with the ability to inactivate bacterial proteins secreted in the
phagocyte cytosol may have crucial importance for bacterial survival within the
phagocyte.
PMID- 25139901
TI - Acquisition and evolution of SXT-R391 integrative conjugative elements in the
seventh-pandemic Vibrio cholerae lineage.
AB - SXT-R391 Integrative conjugative elements (ICEs) are self-transmissible mobile
genetic elements able to confer multidrug resistance and other adaptive features
to bacterial hosts, including Vibrio cholerae, the causative agent of cholera.
ICEs are arranged in a mosaic genetic structure composed of a conserved backbone
interspersed with variable DNA clusters located in conserved hot spots. In this
study, we investigated ICE acquisition and subsequent microevolution in pandemic
V. cholerae. Ninety-six ICEs were retrieved from publicly available sequence
databases from V. cholerae clinical strains and were compared to a set of
reference ICEs. Comparative genomics highlighted the existence of five main ICE
groups with a distinct genetic makeup, exemplified by ICEVchInd5, ICEVchMoz10,
SXT, ICEVchInd6, and ICEVchBan11. ICEVchInd5 (the most frequent element,
represented by 70 of 96 elements analyzed) displayed no sequence rearrangements
and was characterized by 46 single nucleotide polymorphisms (SNPs). SNP analysis
revealed that recent inter-ICE homologous recombination between ICEVchInd5 and
other ICEs circulating in gammaproteobacteria generated ICEVchMoz10, ICEVchInd6,
and ICEVchBan11. Bayesian phylogenetic analyses indicated that ICEVchInd5 and SXT
were independently acquired by the current pandemic V. cholerae O1 and O139
lineages, respectively, within a period of only a few years. IMPORTANCE: SXT-R391
ICEs have been recognized as key vectors of antibiotic resistance in the seventh
pandemic lineage of V. cholerae, which remains a major cause of mortality and
morbidity on a global scale. ICEs were acquired only recently in this clade and
are acknowledged to be major contributors to horizontal gene transfer and the
acquisition of new traits in bacterial species. We have reconstructed the
temporal dynamics of SXT-R391 ICE acquisition and spread and have identified
subsequent recombination events generating significant diversity in ICEs
currently circulating among V. cholerae clinical strains. Our results showed that
acquisition of SXT-R391 ICEs provided the V. cholerae seventh-pandemic lineage
not only with a multidrug resistance phenotype but also with a powerful molecular
tool for rapidly accessing the pan-genome of a large number of
gammaproteobacteria.
PMID- 25139902
TI - Genome-wide mutant fitness profiling identifies nutritional requirements for
optimal growth of Yersinia pestis in deep tissue.
AB - Rapid growth in deep tissue is essential to the high virulence of Yersinia
pestis, causative agent of plague. To better understand the mechanisms underlying
this unusual ability, we used transposon mutagenesis and high-throughput
sequencing (Tn-seq) to systematically probe the Y. pestis genome for elements
contributing to fitness during infection. More than a million independent
insertion mutants representing nearly 200,000 unique genotypes were generated in
fully virulent Y. pestis. Each mutant in the library was assayed for its ability
to proliferate in vitro on rich medium and in mice following intravenous
injection. Virtually all genes previously established to contribute to virulence
following intravenous infection showed significant fitness defects, with the
exception of genes for yersiniabactin biosynthesis, which were masked by strong
intercellular complementation effects. We also identified more than 30 genes with
roles in nutrient acquisition and metabolism as experiencing strong selection
during infection. Many of these genes had not previously been implicated in Y.
pestis virulence. We further examined the fitness defects of strains carrying
mutations in two such genes-encoding a branched-chain amino acid importer (brnQ)
and a glucose importer (ptsG)-both in vivo and in a novel defined synthetic
growth medium with nutrient concentrations matching those in serum. Our findings
suggest that diverse nutrient limitations in deep tissue play a more important
role in controlling bacterial infection than has heretofore been appreciated.
Because much is known about Y. pestis pathogenesis, this study also serves as a
test case that assesses the ability of Tn-seq to detect virulence genes.
IMPORTANCE: Our understanding of the functions required by bacteria to grow in
deep tissues is limited, in part because most growth studies of pathogenic
bacteria are conducted on laboratory media that do not reflect conditions
prevailing in infected animal tissues. Improving our knowledge of this aspect of
bacterial biology is important as a potential pathway to the development of novel
therapeutics. Yersinia pestis, the plague bacterium, is highly virulent due to
its rapid dissemination and growth in deep tissues, making it a good model for
discovering bacterial adaptations that promote rapid growth during infection.
Using Tn-seq, a genome-wide fitness profiling technique, we identified several
functions required for fitness of Y. pestis in vivo that were not previously
known to be important. Most of these functions are needed to acquire or
synthesize nutrients. Interference with these critical nutrient acquisition
pathways may be an effective strategy for designing novel antibiotics and
vaccines.
PMID- 25139903
TI - DNA transport across the outer and inner membranes of naturally transformable
Vibrio cholerae is spatially but not temporally coupled.
AB - The physiological state of natural competence for transformation allows certain
bacteria to take up free DNA from the environment and to recombine such newly
acquired DNA into their chromosomes. However, even though conserved components
that are required to undergo natural transformation have been identified in
several naturally competent bacteria, our knowledge of the underlying mechanisms
of the DNA uptake process remains very limited. To better understand these
mechanisms, we investigated the competence-mediated DNA transport in the
naturally transformable pathogen Vibrio cholerae. Previously, we used a cell
biology-based approach to experimentally address an existing hypothesis, which
suggested the competence protein ComEA plays a role in the DNA uptake process
across the outer membrane of Gram-negative bacteria. Here, we extended this
knowledge by investigating the dynamics of DNA translocation across both
membranes. More precisely, we indirectly visualized the transfer of the external
DNA from outside the cell into the periplasm followed by the shuttling of the DNA
into the cytoplasm. Based on these data, we conclude that for V. cholerae, the
DNA translocation across the outer and inner membranes is spatially but not
temporally coupled. IMPORTANCE: As a mode of horizontal gene transfer, natural
competence for transformation has contributed substantially to the plasticity of
genomes and to bacterial evolution. Natural competence is often a tightly
regulated process and is induced by diverse environmental cues. This is in
contrast to the mechanistic aspects of the DNA translocation event, which are
most likely conserved among naturally transformable bacteria. However, the DNA
uptake process is still not well understood. We therefore investigated how
external DNA reaches the cytosol of the naturally transformable bacterium V.
cholerae. More specifically, we provide evidence that the DNA translocation
across the membranes is spatially but not temporally coupled. We hypothesize that
this model also applies to other competent Gram-negative bacteria and that our
study contributes to the general understanding of this important biological
process.
PMID- 25139904
TI - Annexin A2 mediates Mycoplasma pneumoniae community-acquired respiratory distress
syndrome toxin binding to eukaryotic cells.
AB - Mycoplasma pneumoniae synthesizes a novel human surfactant protein A (SP-A)
binding cytotoxin, designated community-acquired respiratory distress syndrome
(CARDS) toxin, that exhibits ADP-ribosylating and vacuolating activities in
mammalian cells and is directly linked to a range of acute and chronic airway
diseases, including asthma. In our attempt to detect additional CARDS toxin
binding proteins, we subjected the membrane fraction of human A549 airway cells
to affinity chromatography using recombinant CARDS toxin as bait. A 36-kDa A549
cell membrane protein bound to CARDS toxin and was identified by time of flight
(TOF) mass spectroscopy as annexin A2 (AnxA2) and verified by immunoblotting with
anti-AnxA2 monoclonal antibody. Dose-dependent binding of CARDS toxin to
recombinant AnxA2 reinforced the specificity of the interaction, and further
studies revealed that the carboxy terminus of CARDS toxin mediated binding to
AnxA2. In addition, pretreatment of viable A549 cells with anti-AnxA2 monoclonal
antibody or AnxA2 small interfering RNA (siRNA) reduced toxin binding and
internalization. Immunofluorescence analysis of CARDS toxin-treated A549 cells
demonstrated the colocalization of CARDS toxin with cell surface-associated AnxA2
upon initial binding and with intracellular AnxA2 following toxin
internalization. HepG2 cells, which express low levels of AnxA2, were transfected
with a plasmid expressing AnxA2 protein, resulting in enhanced binding of CARDS
toxin and increased vacuolization. In addition, NCI-H441 cells, which express
both AnxA2 and SP-A, upon AnxA2 siRNA transfection, showed decreased binding and
subsequent vacuolization. These results indicate that CARDS toxin recognizes
AnxA2 as a functional receptor, leading to CARDS toxin-induced changes in
mammalian cells. IMPORTANCE: Host cell susceptibility to bacterial toxins is
usually determined by the presence and abundance of appropriate receptors, which
provides a molecular basis for toxin target cell specificities. To perform its
ADP-ribosylating and vacuolating activities, community-acquired respiratory
distress syndrome (CARDS) toxin must bind to host cell surfaces via receptor
mediated events in order to be internalized and trafficked effectively. Earlier,
we reported the binding of CARDS toxin to surfactant protein A (SP-A), and here
we show how CARDS toxin uses an alternative receptor to execute its pathogenic
properties. CARDS toxin binds selectively to annexin A2 (AnxA2), which exists
both on the cell surface and intracellularly. Since AnxA2 regulates membrane
dynamics at early stages of endocytosis and trafficking, it serves as a distinct
receptor for CARDS toxin binding and internalization and enhances CARDS toxin
induced vacuolization in mammalian cells.
PMID- 25139905
TI - Remodeling of the intestinal brush border underlies adhesion and virulence of an
enteric pathogen.
AB - Intestinal colonization by Vibrio parahaemolyticus-the most common cause of
seafood-borne bacterial enteritis worldwide-induces extensive disruption of
intestinal microvilli. In orogastrically infected infant rabbits, reorganization
of the apical brush border membrane includes effacement of some microvilli and
marked elongation of others. All diarrhea, inflammation, and intestinal pathology
associated with V. parahaemolyticus infection are dependent upon one of its type
3 secretion systems (T3SS2); however, translocated effectors that directly
mediate brush border restructuring and bacterial adhesion are not known. Here, we
demonstrate that the effector VopV is essential for V. parahaemolyticus
intestinal colonization and therefore its pathogenicity, that it induces
effacement of brush border microvilli, and that this effacement is required for
adhesion of V. parahaemolyticus to enterocytes. VopV contains multiple
functionally independent and mechanistically distinct domains through which it
disrupts microvilli. We show that interaction between VopV and filamin, as well
as VopV's previously noted interaction with actin, mediates enterocyte
cytoskeletal reorganization. VopV's multipronged approach to epithelial
restructuring, coupled with its impact on colonization, suggests that remodeling
of the epithelial brush border is a critical step in pathogenesis. IMPORTANCE:
Colonization of the small bowel by Vibrio parahaemolyticus, the most common
bacterial agent of seafood-borne enteric disease, induces extensive structural
changes in the intestinal epithelium. Here, we show that this diarrheal
pathogen's colonization and virulence depend upon VopV, a bacterial protein that
is transferred into host epithelial cells. VopV induces marked rearrangement of
the apical epithelial cell membrane, including elimination of microvilli, by two
means: through interaction with actin and through a previously unrecognized
interaction with the actin-cross-linking protein filamin. VopV-mediated
"effacement" of microvilli enables V. parahaemolyticus to adhere to host cells,
although VopV may not directly mediate adhesion. VopV's effects on microvillus
structure and bacterial adhesion likely account for its essential role in V.
parahaemolyticus intestinal pathogenesis. Our findings suggest a new role for
filamin in brush border maintenance and raise the possibility that microvillus
effacement is a common strategy among enteric pathogens for enhancing adhesion to
host cells.
PMID- 25139907
TI - Young patients with hypertrophic cardiomyopathy, but not subjects at risk, show
decreased myocardial perfusion reserve quantified with CMR.
AB - AIMS: To determine if myocardial perfusion (MP) during hyperaemia is decreased in
young patients with hypertrophic cardiomyopathy (HCM). Also, to determine if an
MP decrease is associated with diastolic dysfunction, and to investigate if young
subjects at risk of HCM show differences in MP compared with controls. METHODS
AND RESULTS: This study included 10 HCM patients (age 22.3 +/- 6.4 years), 14
subjects at risk for HCM 'HCM risk' (age 18.9 +/- 3.8 years), and 12 controls
(age 22.8 +/- 4.5 years). HCM patients were examined at rest and during
hyperaemia (adenosine 140 ug/kg/min) with cardiovascular magnetic resonance (CMR)
and echocardiography. MP was calculated as the ratio of coronary sinus flow and
left ventricular mass (LVM) from CMR. Myocardial fibrosis was assessed using late
gadolinium enhancement. Diastolic function was quantified with both
echocardiography and CMR. At rest, MP (mL/min/g) was similar in the control, HCM
risk, and HCM patients (0.8 +/- 0.1, 1.0 +/- 0.1, and 0.9 +/- 0.1, respectively,
P = ns). During adenosine, MP was lower in HCM patients (2.5 +/- 0.4, P < 0.05)
compared with both HCM risk (5.0 +/- 0.5) and controls (3.9 +/- 0.3). Subjects at
HCM risk showed no significant difference in MP during adenosine compared with
controls. One HCM patient showed mild diastolic dysfunction. Neither controls nor
HCM risk individuals showed any sign of myocardial fibrosis, whereas 7/10 HCM
patients had fibrosis (5 +/- 1% of the total LVM). CONCLUSION: Young individuals
with HCM, but not those at risk, show decreased MP during hyperaemia compared
with controls even in the absence of diastolic dysfunction or LV outflow
obstruction. These results may suggest that microvascular disease contributes to
the decreased MP in the investigated population.
PMID- 25139906
TI - Echocardiographic findings in simple and complex patent foramen ovale before and
after transcatheter closure.
AB - AIMS: Percutaneous closure of patent foramen ovale (PFO) in cryptogenic
cerebrovascular events is an alternative to medical therapy. The interpretation
of residual shunts after implantation of different devices for PFO with different
morphologies is controversial. METHODS AND RESULTS: Transcatheter PFO closure was
performed in 123 patients with a history of >=1 paradoxical embolism using three
different devices: Amplatzer (n = 46), Figulla Occlutech (n = 41), and Atriasept
Cardia (n = 36). Fifty-six patients presented with simple PFO and 67 patients had
complex morphologies. All patients were studied with contrast enhanced
transesophageal echocardiography (TEE) before interventional procedure and
thereafter at 1 and 6 months and every 6-12 months in case of incomplete closure.
Definite closure was confirmed in at least two consecutive TEE studies. Various
PFO morphologies were identified by TEE before device implantation. The device
size to PFO diameter ratio was significantly increased in patients with complex
PFO compared with those patients with a simple PFO morphology (P < 0.05). The
difference between the closure rate of S-PFO and C-PFO concerning each device
type was significant (Amplatzer P = 0.0027, Figulla P = 0.0043, and Atriasept P <
0.01). The mean follow-up period was 3.4 years (median 2.7 years) with a
cerebrovascular re-event rate of 2.4% per year. In three patients, thrombi were
detected in the 6-month TEE controls and resolved after medical therapy. In three
other patients, the implantation of an adjunctive device was necessary for
residual shunt. CONCLUSION: In our series of patients, the closure rate was
dependent on PFO morphology more than occluder size and type. An adjunctive
device was implanted in selected cases.
PMID- 25139908
TI - Three-dimensional transoesophageal echocardiographic visualization of malignant
anomalous left main coronary origin and course causing sudden cardiac death.
PMID- 25139909
TI - Selection of chromosomal DNA libraries using a multiplex CRISPR system.
AB - The directed evolution of biomolecules to improve or change their activity is
central to many engineering and synthetic biology efforts. However, selecting
improved variants from gene libraries in living cells requires plasmid expression
systems that suffer from variable copy number effects, or the use of complex
marker-dependent chromosomal integration strategies. We developed quantitative
gene assembly and DNA library insertion into the Saccharomyces cerevisiae genome
by optimizing an efficient single-step and marker-free genome editing system
using CRISPR-Cas9. With this Multiplex CRISPR (CRISPRm) system, we selected an
improved cellobiose utilization pathway in diploid yeast in a single round of
mutagenesis and selection, which increased cellobiose fermentation rates by over
10-fold. Mutations recovered in the best cellodextrin transporters reveal synergy
between substrate binding and transporter dynamics, and demonstrate the power of
CRISPRm to accelerate selection experiments and discoveries of the molecular
determinants that enhance biomolecule function.
PMID- 25139910
TI - Determining protein complex structures based on a Bayesian model of in vivo
Forster resonance energy transfer (FRET) data.
AB - The use of in vivo Forster resonance energy transfer (FRET) data to determine the
molecular architecture of a protein complex in living cells is challenging due to
data sparseness, sample heterogeneity, signal contributions from multiple donors
and acceptors, unequal fluorophore brightness, photobleaching, flexibility of the
linker connecting the fluorophore to the tagged protein, and spectral cross-talk.
We addressed these challenges by using a Bayesian approach that produces the
posterior probability of a model, given the input data. The posterior probability
is defined as a function of the dependence of our FRET metric FRETR on a
structure (forward model), a model of noise in the data, as well as prior
information about the structure, relative populations of distinct states in the
sample, forward model parameters, and data noise. The forward model was validated
against kinetic Monte Carlo simulations and in vivo experimental data collected
on nine systems of known structure. In addition, our Bayesian approach was
validated by a benchmark of 16 protein complexes of known structure. Given the
structures of each subunit of the complexes, models were computed from synthetic
FRETR data with a distance root-mean-squared deviation error of 14 to 17 A. The
approach is implemented in the open-source Integrative Modeling Platform,
allowing us to determine macromolecular structures through a combination of in
vivo FRETR data and data from other sources, such as electron microscopy and
chemical cross-linking.
PMID- 25139912
TI - External manifestations of Gardner's syndrome as the presenting clinical entity.
AB - Gardner's syndrome is an autosomal dominant disease characterised by the presence
of colonic polyposis, osteomas and a multitude of soft tissue tumours.
Pathological features such as osteomas of the mandible, skull and facial skeleton
are unaesthetic as well as incapacitating. We present the case of a 22-year-old
man with pain and discharge from the left eye and a firm swelling in the left
infraorbital region leading to proptosis of the left eye. A detailed examination
of the patient led to the presence of a large osteoma in the left orbital region,
multiple cystic lesion, corneal opacity and parapapillary atrophy in the left
eye. Radiography revealed the presence of multiple unerupted supernumerary teeth
and osteomas. Colonoscopic findings showed the presence of multiple polyps. Thus,
external manifestations of the patient's facial region led to the establishment
of the diagnosis of Gardner's syndrome. The importance of our case highlights the
necessity of maintaining a high vigilance with regard to the occurrence of such
an entity.
PMID- 25139913
TI - Periorbital purpura (raccoon's eyes).
PMID- 25139914
TI - Gingival squamous cell carcinoma presenting as periodontal lesion in the
mandibular posterior region.
AB - Gingival squamous cell carcinoma (GSCC) is a relatively rare malignant neoplasm
of the oral cavity. It represents less than 10% of diagnosed intraoral carcinoma.
Because of its close proximity to the teeth and periodontium, the tumour can
mimic tooth-related benign inflammatory conditions. This case report describes a
patient diagnosed with GSCC presenting as localised periodontitis.
PMID- 25139911
TI - Integrative structure-function mapping of the nucleoporin Nup133 suggests a
conserved mechanism for membrane anchoring of the nuclear pore complex.
AB - The nuclear pore complex (NPC) is the sole passageway for the transport of
macromolecules across the nuclear envelope. Nup133, a major component in the
essential Y-shaped Nup84 complex, is a large scaffold protein of the NPC's outer
ring structure. Here, we describe an integrative modeling approach that produces
atomic models for multiple states of Saccharomyces cerevisiae (Sc) Nup133, based
on the crystal structures of the sequence segments and their homologs, including
the related Vanderwaltozyma polyspora (Vp) Nup133 residues 55 to 502 (VpNup133(55
502)) determined in this study, small angle X-ray scattering profiles for 18
constructs of ScNup133 and one construct of VpNup133, and 23 negative-stain
electron microscopy class averages of ScNup133(2-1157). Using our integrative
approach, we then computed a multi-state structural model of the full-length
ScNup133 and validated it with mutational studies and 45 chemical cross-links
determined via mass spectrometry. Finally, the model of ScNup133 allowed us to
annotate a potential ArfGAP1 lipid packing sensor (ALPS) motif in Sc and VpNup133
and discuss its potential significance in the context of the whole NPC; we
suggest that ALPS motifs are scattered throughout the NPC's scaffold in all
eukaryotes and play a major role in the assembly and membrane anchoring of the
NPC in the nuclear envelope. Our results are consistent with a common
evolutionary origin of Nup133 with membrane coating complexes (the protocoatomer
hypothesis); the presence of the ALPS motifs in coatomer-like nucleoporins
suggests an ancestral mechanism for membrane recognition present in early
membrane coating complexes.
PMID- 25139915
TI - Psychosis with Huntington's disease: role of antipsychotic medications.
AB - This is a case of a 60-year-old man who presented with a 6-month history of
increasing agitation and emotional volatility. His family brought him to the
emergency room as they were concerned about his threatening and aggressive
behaviour. The patient was initially incoherent and uncooperative. During the
interview, the patient's family revealed that he had a previous diagnosis of
Huntington's disease; there was also a family history of personality changes
preceding Huntington's chorea. The patient was admitted to the psychiatric
inpatient unit and started on low-dose risperidone. Consequently, there was
marked improvement in his symptoms. Subsequent cognitive tests revealed deficits
in multiple domains. After a month, the patient was discharged to a community
home in stable state.
PMID- 25139916
TI - Disseminated histoplasmosis in an HIV patient with CD4 count of 1 cell/uL.
AB - We report a case of a young woman with advanced HIV/AIDS who presented with a
short duration of fever and shortness of breath, with no recent travel history or
previous hospitalisation, accompanied by non-specific abdominal symptoms and
suspicious upper gastrointestinal bleed. Her CD4 count was 1 cell/MUL raising the
suspicious for various opportunistic aetiologies. The initial suspicion was for
pneumocystis pneumonia (PCP) and the patient was treated empirically with
antimicrobials. Peripheral smear findings, urinary antigen tests and
bronchoalveolar lavage (BAL) were suggestive of disseminated histoplasmosis. PCP
was ruled out in BAL. Transabdominal imaging was concerning for periaortic
lymphadenopathy raising the suspicion of occult malignancy. Endoscopic evaluation
of her digestive tract was unrevealing. Endoscopic ultrasound fine-needle
aspiration (EUS-FNA) confirmed histoplasmosis. She received a liposomal
amphotericin B for 10 days followed by itraconazole with significant improvement.
Her CD4 count was found to be the lowest reported count with a single
opportunistic pathogen.
PMID- 25139917
TI - The disappearing clip: an unusual complication in MRI biopsy.
AB - MRI-guided biopsies are being increasingly used for otherwise occult breast
lesions. Clip migration has been reported however, to the best of our knowledge,
there have been no documented cases of entire disappearance of a marker clip.
Absence of the postbiopsy marker clip was noted when our patient returned for
preoperative hook-wire localisation even though accurate clip placement had been
confirmed on the post-MRI biopsy mammogram.
PMID- 25139919
TI - Fatal measles presenting as acute respiratory distress syndrome in an
immunocompetent adult.
AB - Fatal measles is known to occur among immunocompromised adults. We report a rare
case of an immunocompetent non-pregnant young lady who suffered from fatal acute
respiratory distress syndrome due to measles. Physicians must be vigilant to this
deadly presentation of measles even in immunocompetent individuals. We emphasise
the inadequacies of vaccination programmes in India reflected not only by the
existing high measles-related childhood mortalities, but also an emerging rise in
deaths among adults.
PMID- 25139918
TI - Parathyroid carcinoma, a rare cause of primary hyperparathyroidism.
AB - A 45 year-old woman who presented with non-specific neck and shoulder pain, was
found to have mild hypercalcaemia, markedly elevated parathyroid hormone levels,
and an irregular parathyroid gland on imaging. The patient underwent a
parathyroidectomy and the pathology report came back positive for parathyroid
carcinoma with muscular invasion. Parathyroid carcinoma is an exceptionally rare
cause of primary hyperparathyroidism and can have a poor prognosis due to
metastases and a high propensity to recur after resection. Reports of non
functioning parathyroid carcinomas tend to behave even more aggressively. Repeat
imaging on this patient showed residual cancer present, so the patient underwent
a second surgery with radical neck dissection and has since been doing very well
postoperatively. Diagnosis and treatment is challenging and it is critical to
continuously follow-up for recurrent disease.
PMID- 25139920
TI - An unusual cause of haemoptysis: isolated tracheobronchial amyloidosis.
PMID- 25139921
TI - Eyelid reanimation, neurotisation, and transplantation of the cornea in a patient
with facial palsy.
AB - Patients affected by facial palsy suffer from failure to fully close the eyelids;
the resulting eye exposure can lead to dry eye syndrome, loss of epithelial
integrity, corneal ulceration and infections. Corneal anaesthesia exacerbates
risk of corneal damage in these patients. Eyelid paralysis-associated corneal
lesions may induce severe visual impairment, for which the ideal treatment is
corneal transplantation, a procedure contraindicated in patients with corneal
sensitivity and inadequate eyelid closure. We present the case of a patient
affected by unilateral facial palsy associated with corneal anaesthesia, due to
seventh and fifth cranial nerve damage following homolateral eighth cranial nerve
surgery. The patient underwent surgery to re-establish eyelid and corneal
competence, and then received a corneal graft with consequent amelioration of
visual acuity. This is the first case of associated corneal anaesthesia and
facial palsy that was comprehensively treated with a set of surgical procedures,
including a corneal transplant.
PMID- 25139922
TI - Transient cefuroxime/metronidazole treatment induced factor V antibodies.
AB - A 29-year-old patient presented with an appendicular infiltrate, initially
treated with intravenous antibiotics, but later requiring percutaneous drainage.
Both prothrombin time (PT) and activated partial thromboplastin time (aPTT) were
prolonged on 3 days of antibiotic treatment and unresponsive to vitamin K or
prothrombin complex concentrate. Laboratory investigation ultimately showed
reduced factor V activity and factor V antibodies. In contrast to previously
described cases of factor V antibodies, PT and aPTT were only mildly prolonged
and residual factor V activity was still >20%. Draining of the abscess did not
induce significant bleeding. Afterwards, no haemostatic medication was required.
The patient was discharged from the hospital without complications. One week
after cessation of the antibiotic treatment, PT and aPTT were within normal range
again, with a factor V activity level of 36%. In conclusion, we present a patient
with transient factor V antibodies, induced by antibiotics, without clinical
bleeding tendency.
PMID- 25139923
TI - Post-traumatic iridodialysis, crystalline dislocation and vitreous haemorrhage:
how to manage.
AB - A 66-year-old man, while taking care of his horse, sustained a blunt, non
penetrating injury to the right side of his face, which damaged his eye. On slit
lamp examination, iris dialysis and crystalline dislocation in the vitreous
chamber were observed. On presentation, his best correct visual acuity was hand
motion. A 23 G vitrectomy and subsequently an iris reconstruction and a glued
intraocular lens implant were performed. Visual acuity reached +0.1 logMAR 1
month after surgery and remained stable after 12 months' follow-up.
PMID- 25139924
TI - Haemophagocytic lymphohistiocytosis associated with coccidiomycosis.
AB - Haemophagocytic lymphohistiocytosis (HLH) is a rapidly fatal disease caused by
dysregulated histiocytes leading to an excessive inflammatory reaction. While
genetic forms of HLH exist, the most common form is acquired, frequently
associated with infection. Here we report the first case of HLH associated with a
coccidiomycosis infection. This patient is a 13-year-old previously healthy boy
who presented with a flu-like illness, which rapidly progressed to refractory
shock, severe ARDS, multiorgan failure and death despite maximal medical therapy,
including broad-spectrum antibiotics to treat well-established causes of acquired
HLH. Autopsy findings revealed the diagnosis of HLH in the setting of pulmonary
coccidiomycosis. Antifungal therapy should be considered in cases of acquired HLH
when the underlying aetiology is not clear.
PMID- 25139925
TI - Giant suprasellar arachnoid cyst presenting with precocious puberty.
PMID- 25139926
TI - Obstructed ileostomy in the third trimester of pregnancy due to compression from
the gravid uterus: diagnosis and management.
AB - Ileostomy obstruction in pregnancy, although rare, is a significant complication
with associated morbidity and mortality. Early studies recommended immediate
surgical intervention for cases of ileostomy obstruction in pregnancy. We present
a case of ileostomy obstruction at 29-week gestation in which a laparotomy was
performed for presumed adhesions. When adhesiolysis failed to resolve the
obstruction, it became clear that the obstruction was caused by external
compression from the enlarging gravid uterus. The remainder of the pregnancy was
successfully managed by daily aspiration of bowel contents using a large bore
drainage tube, and total parental nutrition. Recent studies have utilised MRI to
distinguish between adhesions and uterine compression as the cause of ileostomy
obstruction in pregnancy. In the few cases of obstruction caused by uterine
compression, patients have been safely managed with conservative therapy, thereby
avoiding the risks of surgery.
PMID- 25139927
TI - Urinoma formation following laparoscopic oophorectomy.
PMID- 25139928
TI - A giant myxoma arising from the free wall of the right atria.
PMID- 25139929
TI - Mislaid dentures: a cause for unusual presentation of bilateral vocal cord palsy.
AB - An 81-year-old man was referred urgently to the head and neck clinic with
symptoms of worsening dysphagia, dysphonia and weight loss. He had a history of
chronic lymphocytic leukaemia. On full ear, nose and throat examination, he was
found to have fixed vocal cords with pooling of saliva in the bilateral pyriform
fossa. Hypopharyngeal malignancy was suspected and further imaging was performed.
Imaging also raised the suspicion of malignancy in the hypopharynx. Rigid
endoscopic examination under general anaesthesia was carried out which revealed
an impacted denture in the cricopharynx and upper oesophagus. The patient was
aware of his loss of dentures 3 months ago (corresponds to the onset of his
symptoms) but felt that he had mislaid them and had never mentioned this to
anyone. We present a case highlighting a delay in diagnosis, a missed diagnosis
on CT scan and an unusual presentation leading to bilateral vocal cord paresis.
PMID- 25139930
TI - Editorial.
PMID- 25139931
TI - A reflection of outcomes research and its impact on the practice of hand surgery.
PMID- 25139932
TI - One mum too few: maternal status in host surrogate motherhood arrangements.
AB - In a host surrogate motherhood arrangement, the surrogate agrees to be implanted
with, and carry to term, an embryo created from the commissioning couple's
gametes. When the surrogate child is born, it is the surrogate mother who,
according to UK law, holds the legal status of mother. By contrast, the
commissioning mother possesses no maternal status and she can only attain it once
the surrogate agrees to the completion of the arrangement. One consequence of
this is that, in the event that a host arrangement fails, the commissioning
mother is left without maternal status. In this paper, I argue that this denial
of maternal status misrepresents the commissioning mother's role in the host
arrangement and her relationship with the surrogate child. Consequently, I
suggest that commissioning mothers participating in host surrogacy arrangements
ought to be granted the status of mother in the event that the arrangement fails.
PMID- 25139933
TI - A case of consent.
PMID- 25139934
TI - Forced-Attention Dichotic Listening With University Students With Dyslexia:
Search for a Core Deficit.
AB - Rapidly changing environments in day-to-day activities, enriched with stimuli
competing for attention, require a cognitive control mechanism to select relevant
stimuli, ignore irrelevant stimuli, and shift attention between alternative
features of the environment. Such attentional orchestration is essential to the
acquisition of reading skills. In the present forced attention dichotic listening
study, adults with moderate and severe dyslexia and nondisabled adults were
tested on their ability to switch attention between ears for immediate recall.
Blocks of pairs of consonant-vowel syllables were counterbalanced into left-ear
first or right-ear first ordered conditions. Significant order effects showed
that only those with severe dyslexia were poorer in switching attention to the
left ear, whereas both groups with dyslexia were poorer switching attention to
the right ear. Shifting left appears to be a normative function of reading level,
whereas inferior ability to disengage attending to the left ear to report from
the right ear qualifies as a dysfunctional facet of dyslexia with etiological
significance. No support was found for the traditional proposition that dyslexia
may be associated with atypical left hemisphere lateralization. Combining these
results with previous dichotic and neuroimaging research implicates a
dysfunctional frontostriatal cognitive control network in dyslexia. With due
caution, the results suggest that a neurobiological feature of dyslexia may be a
lack of control in downwardly modulating excessive left inferior frontal cortex
activations. The results are consistent with impoverished connectedness between
left anterior and posterior language areas and, pending future confirmation of
these findings, suggest the need for a reconceptualization of remedial
programming.
PMID- 25139935
TI - Comparison of mammographic density assessed as volumes and areas among women
undergoing diagnostic image-guided breast biopsy.
AB - BACKGROUND: Mammographic density (MD), the area of non-fatty-appearing tissue
divided by total breast area, is a strong breast cancer risk factor. Most MD
analyses have used visual categorizations or computer-assisted quantification,
which ignore breast thickness. We explored MD volume and area, using a volumetric
approach previously validated as predictive of breast cancer risk, in relation to
risk factors among women undergoing breast biopsy. METHODS: Among 413 primarily
white women, ages 40 to 65 years, undergoing diagnostic breast biopsies between
2007 and 2010 at an academic facility in Vermont, MD volume (cm(3)) was
quantified in craniocaudal views of the breast contralateral to the biopsy target
using a density phantom, whereas MD area (cm(2)) was measured on the same digital
mammograms using thresholding software. Risk factor associations with continuous
MD measurements were evaluated using linear regression. RESULTS: Percent MD
volume and area were correlated (r = 0.81) and strongly and inversely associated
with age, body mass index (BMI), and menopause. Both measures were inversely
associated with smoking and positively associated with breast biopsy history.
Absolute MD measures were correlated (r = 0.46) and inversely related to age and
menopause. Whereas absolute dense area was inversely associated with BMI,
absolute dense volume was positively associated. CONCLUSIONS: Volume and area MD
measures exhibit some overlap in risk factor associations, but divergence as
well, particularly for BMI. IMPACT: Findings suggest that volume and area density
measures differ in subsets of women; notably, among obese women, absolute density
was higher with volumetric methods, suggesting that breast cancer risk
assessments may vary for these techniques.
PMID- 25139937
TI - Association of leukocyte mitochondrial DNA copy number with colorectal cancer
risk: Results from the Shanghai Women's Health Study.
AB - BACKGROUND: Mitochondria play an important role in cellular energy metabolism,
free radical production, and apoptosis, and thus may be involved in cancer
development. METHODS: We evaluated mitochondrial DNA (mtDNA) copy number in
peripheral leukocytes in relation to colorectal cancer risk in a case-control
study of 444 colorectal cancer cases and 1,423 controls nested in the Shanghai
Women's Health Study, a population-based, prospective cohort study. Relative
mtDNA copy number was determined by a quantitative real-time PCR assay using
peripheral leukocyte DNA samples collected at the time of study enrollment,
before cancer diagnosis. RESULTS: We found that baseline mtDNA copy number was
lower among women who subsequently developed colorectal cancer [geometric mean,
0.277; 95% confidence interval (CI), 0.269-0.285] than among women who remained
cancer-free (geometric mean, 0.288; 95% CI, 0.284-0.293; P = 0.0153).
Multivariate adjusted ORs were 1.26 (95% CI, 0.93-1.70) and 1.44 (95% CI, 1.06
1.94) for the middle and lower tertiles of mtDNA copy number, respectively,
compared with the upper tertile (highest mtDNA copy number; Ptrend = 0.0204). The
association varied little by the interval between blood collection and cancer
diagnosis. CONCLUSIONS: Our data suggest that mtDNA copy number measured in
peripheral leukocytes may be a potential biomarker useful for colorectal cancer
risk assessment. IMPACT: If confirmed, mtDNA copy number measured in peripheral
leukocytes may be a biomarker useful for colorectal cancer risk assessment.
PMID- 25139938
TI - What is the risk of having a total hip or knee replacement for patients with
lupus?
AB - Individuals with systemic lupus erythematosus (SLE) frequently have arthralgia
but joint damage leading to surgery is thought to be less common. In addition to
inflammatory damage, other reasons like avascular necrosis (AVN), which is often
associated with steroid use, excessive alcohol intake and antiphospholipid
syndrome (APS), may increase the likelihood of large joint failure. In this study
we aimed to determine the likelihood of having a total hip replacement (THR) or
total knee replacement (TKR) for individuals with SLE compared to those without
lupus, by performing a retrospective matched case control study of all THRs and
TKRs that were performed between 1991 and 2011 and recorded in the General
Practice Research Database (GPRD). Individuals with inflammatory arthritis due to
any other causes were excluded and the results were adjusted for steroid use,
alcohol consumption (drinking status) and APS. The results show that patients
with lupus who had a THR or TKR were younger than their peers without lupus. In
addition, they appeared to have a significantly increased risk of TKR but the
increased risk of THR did not remain after adjustment for steroid use, alcohol
consumption and APS.
PMID- 25139936
TI - Association of cancer susceptibility variants with risk of multiple primary
cancers: The population architecture using genomics and epidemiology study.
AB - BACKGROUND: Multiple primary cancers account for approximately 16% of all
incident cancers in the United States. Although genome-wide association studies
(GWAS) have identified many common genetic variants associated with various
cancer sites, no study has examined the association of these genetic variants
with risk of multiple primary cancers (MPC). METHODS: As part of the National
Human Genome Research Institute (NHGRI) Population Architecture using Genomics
and Epidemiology (PAGE) study, we used data from the Multiethnic Cohort (MEC) and
Women's Health Initiative (WHI). Incident MPC (IMPC) cases (n = 1,385) were
defined as participants diagnosed with more than one incident cancer after cohort
entry. Participants diagnosed with only one incident cancer after cohort entry
with follow-up equal to or longer than IMPC cases served as controls (single
index cancer controls; n = 9,626). Fixed-effects meta-analyses of unconditional
logistic regression analyses were used to evaluate the associations between 188
cancer risk variants and IMPC risk. To account for multiple comparisons, we used
the false-positive report probability (FPRP) to determine statistical
significance. RESULTS: A nicotine dependence-associated and lung cancer variant,
CHRNA3 rs578776 [OR, 1.16; 95% confidence interval (CI), 1.05-1.26; P = 0.004],
and two breast cancer variants, EMBP1 rs11249433 and TOX3 rs3803662 (OR, 1.16;
95% CI, 1.04-1.28; P = 0.005 and OR, 1.13; 95% CI, 1.03-1.23; P = 0.006), were
significantly associated with risk of IMPC. The associations for rs578776 and
rs11249433 remained (P < 0.05) after removing subjects who had lung or breast
cancers, respectively (P <= 0.046). These associations did not show significant
heterogeneity by smoking status (Pheterogeneity >= 0.53). CONCLUSIONS: Our study
has identified rs578776 and rs11249433 as risk variants for IMPC. IMPACT: These
findings may help to identify genetic regions associated with IMPC risk.
PMID- 25139939
TI - A new trick for an ancient drug: quinine dissociates antiphospholipid immune
complexes.
AB - Quinine, a quinoline derivative, is an ancient antipyretic drug with antimalarial
properties that has been phased out by more effective synthetic candidates. In
previous studies we discovered that hydroxychloroquine (HCQ), a synthetic
antimalarial with structural similarities to quinine, reduced the binding of
antiphospholipid (aPL) immune complexes to phospholipid bilayers. We performed
ellipsometry and atomic force microscopy (AFM) studies to measure the effect of
quinine on dissociation of anti-beta2-glycoprotein I (anti-beta2GPI) immune
complexes. We found that quinine desorbed pre-formed beta2GPI-aPL immunoglobulin
(Ig)G complexes from phospholipid bilayers at significantly lower molar
concentrations than HCQ. Quinine also inhibited the formation of immune complexes
with a higher efficacy than HCQ at equivalent drug concentrations of 0.2 mg/ml
(0.192 +/- 0.025 ug/cm(2) for quinine vs. 0.352 +/- 0.014 ug/cm(2) for HCQ, p <
0.001). Furthermore, AFM imaging experiments revealed that addition of quinine
disintegrated immune complexes bound to planar phospholipid layers. The
desorptive and inhibitory effects of the old drug, quinine, toward beta2GPI-aPL
IgG complexes and beta2GPI were significantly more pronounced compared to the
synthetic antimalarial, HCQ. The results suggest that the quinoline core of the
molecule is a critical domain for this activity and that side chains may further
modulate this effect. The results also indicate that there may yet be room for
considering new activities of very old drugs in devising clinical trials on
potential non-anticoagulant treatments for antiphospholipid syndrome (APS).
PMID- 25139940
TI - Fatal tusk injuries from a wild boar attack.
AB - Injuries caused by wild boar attacks are rare. The pattern of the tusk injuries
by wild boar is rarely been mentioned in literature. Such injuries can be termed
"tusk injuries". Herein, we discuss the pattern of a wild boar tusk wound
following an attack on a 65-year-old man who sustained fatal injuries as a
result.
PMID- 25139943
TI - Atrophy and structural variability of the upper cervical cord in early multiple
sclerosis.
AB - BACKGROUND: Despite agreement about spinal cord atrophy in progressive forms of
multiple sclerosis (MS), data on clinically isolated syndrome (CIS) and relapsing
remitting MS (RRMS) are conflicting. OBJECTIVE: To determine the onset of spinal
cord atrophy in the disease course of MS. METHODS: Structural brain magnetic
resonance imaging (MRI) was acquired from 267 patients with CIS (85) or RRMS
(182) and 64 healthy controls (HCs). The upper cervical cord cross-sectional area
(UCCA) was determined at the level of C2/C3 by a segmentation tool and adjusted
for focal MS lesions. The coefficient of variation (CV) was calculated from all
measurements between C2/C3 and 13 mm above as a measure of structural
variability. RESULTS: Compared to HCs (76.1+/-6.9 mm(2)), UCCA was significantly
reduced in CIS patients (73.5+/-5.8 mm(2), p=0.018) and RRMS patients (72.4+/-7.0
mm(2), p<0.001). Structural variability was higher in patients than in HCs,
particularly but not exclusively in case of focal lesions (mean CV HCs/patients
without/with lesions: 2.13%/2.55%/3.32%, all p-values<0.007). UCCA and CV
correlated with Expanded Disability Status Scale (EDSS) scores (r =-0.131/0.192,
p=0.044/<0.001) and disease duration (r=-0.134/0.300, p=0.039/< 0.001). CV
additionally correlated with hand and arm function (r=0.180, p=0.014).
CONCLUSION: In MS, cervical cord atrophy already occurs in CIS. In early stages,
structural variability may be a more meaningful marker of spinal cord pathology
than atrophy.
PMID- 25139941
TI - Cortical Brain Activity Reflecting Attentional Biasing Toward Reward-Predicting
Cues Covaries with Economic Decision-Making Performance.
AB - Adaptive choice behavior depends critically on identifying and learning from
outcome-predicting cues. We hypothesized that attention may be preferentially
directed toward certain outcome-predicting cues. We studied this possibility by
analyzing event-related potential (ERP) responses in humans during a
probabilistic decision-making task. Participants viewed pairs of outcome
predicting visual cues and then chose to wager either a small (i.e., loss
minimizing) or large (i.e., gain-maximizing) amount of money. The cues were
bilaterally presented, which allowed us to extract the relative neural responses
to each cue by using a contralateral-versus-ipsilateral ERP contrast. We found an
early lateralized ERP response, whose features matched the attention-shift
related N2pc component and whose amplitude scaled with the learned reward
predicting value of the cues as predicted by an attention-for-reward model.
Consistently, we found a double dissociation involving the N2pc. Across
participants, gain-maximization positively correlated with the N2pc amplitude to
the most reliable gain-predicting cue, suggesting an attentional bias toward such
cues. Conversely, loss-minimization was negatively correlated with the N2pc
amplitude to the most reliable loss-predicting cue, suggesting an attentional
avoidance toward such stimuli. These results indicate that learned stimulus
reward associations can influence rapid attention allocation, and that
differences in this process are associated with individual differences in
economic decision-making performance.
PMID- 25139944
TI - A rare case of hyponatremia from a hypothalamic lesion in a patient with multiple
sclerosis.
AB - The syndrome of inappropriate antidiuretic hormone secretion (SIADH) can occur
from a variety of neurologic and systemic processes; however, it has rarely been
seen in multiple sclerosis (MS). We report a case of SIADH in a patient with MS
and compare it with previously reported English-only cases. A 32-year-old woman
experienced generalized fatigue followed by confusion and was found to have
profound hyponatremia. Her work-up demonstrated SIADH secondary to a discrete
enhancing hypothalamic lesion. Despite the seldom occurrence of SIADH in MS,
hypothalamic lesions are more common than appreciated and should be considered in
patients presenting with hyponatremia or endocrinopathy symptoms.
PMID- 25139945
TI - Paroxysmal dysarthria ataxia syndrome responds to lacosamide.
PMID- 25139946
TI - Cortical thickness and surface area relate to specific symptoms in early
relapsing-remitting multiple sclerosis.
AB - BACKGROUND: Cortical atrophy is common in early relapsing-remitting multiple
sclerosis (RRMS). Whether this atrophy is caused by changes in cortical thickness
or cortical surface area is not known, nor is their separate contributions to
clinical symptoms. OBJECTIVES: To investigate the difference in cortical surface
area, thickness and volume between early RRMS patients and healthy controls; and
the relationship between these measures and neurological disability, cognitive
decline, fatigue and depression. METHODS: RRMS patients (n = 61) underwent
magnetic resonance imaging (MRI), neurological and neuropsychological
examinations. We estimated cortical surface area, thickness and volume and
compared them with matched healthy controls (n = 61). We estimated the
correlations between clinical symptoms and cortical measures within the patient
group. RESULTS: We found no differences in cortical surface area, but widespread
differences in cortical thickness and volume between the groups. Neurological
disability was related to regionally smaller cortical thickness and volume.
Better verbal memory was related to regionally larger surface area; and better
visuo-spatial memory, to regionally larger cortical volume. Higher depression
scores and fatigue were associated with regionally smaller cortical surface area
and volume. CONCLUSIONS: We found that cortical thickness, but not cortical
surface area, is affected in early RRMS. We identified specific structural
correlates to the main clinical symptoms in early RRMS.
PMID- 25139948
TI - Deletion of the Synechocystis sp. PCC 6803 kaiAB1C1 gene cluster causes impaired
cell growth under light-dark conditions.
AB - In contrast to Synechococcus elongatus PCC 7942, few data exist on the timing
mechanism of the widely used cyanobacterium Synechocystis sp. PCC 6803. The
standard kaiAB1C1 operon present in this organism was shown to encode a
functional KaiC protein that interacted with KaiA, similar to the S. elongatus
PCC 7942 clock. Inactivation of this operon in Synechocystis sp. PCC 6803
resulted in a mutant with a strong growth defect when grown under light-dark
cycles, which was even more pronounced when glucose was added to the growth
medium. In addition, mutants showed a bleaching phenotype. No effects were
detected in mutant cells grown under constant light. Microarray experiments
performed with cells grown for 1 day under a light-dark cycle revealed many
differentially regulated genes with known functions in the DeltakaiABC mutant in
comparison with the WT. We identified the genes encoding the cyanobacterial
phytochrome Cph1 and the light-repressed protein LrtA as well as several
hypothetical ORFs with a complete inverse behaviour in the light cycle. These
transcripts showed a stronger accumulation in the light but a weaker accumulation
in the dark in DeltakaiABC cells in comparison with the WT. In general, we found
a considerable overlap with microarray data obtained for hik31 and sigE mutants.
These genes are known to be important regulators of cell metabolism in the dark.
Strikingly, deletion of the DeltakaiABC operon led to a much stronger phenotype
under light-dark cycles in Synechocystis sp. PCC 6803 than in Synechococcus sp.
PCC 7942.
PMID- 25139950
TI - Epidemiological survey of head and neck injuries and trauma in the United States.
AB - OBJECTIVE: Head and neck trauma results in a range of injuries, spanning minor
lacerations to life-threatening airway compromise. Few studies provide in-depth
analysis of injuries to the head and neck (HN). We aim to (1) describe HN injury
prevalence in the US and (2) investigate patient disposition and the outcome of
mortality. STUDY DESIGN: Case series with chart review. SETTING: Nationwide
emergency department (ED) sample. METHODS: The 2011 database was queried for
encounters with a primary diagnosis of HN injury, as categorized by the Barell
Injury Matrix. Weighted estimates for demographics, injury category, and
mechanism were extracted. Predictors of mortality and admission were determined
by multivariable regression. RESULTS: We identified 131 million ED encounters. A
weighted total of 5,418,539 visits were related to primary HN injuries. Average
age was 30 (SE = 0.4), and 56.8% were male. Sixty-four percent of injuries were
attributed to fall or blunt trauma. Open wounds comprised 41.8% of injuries. The
most common procedure was laceration repair (70%). The majority of patients (97%)
were discharged home. Mortality rate was less than 1%. Predictors of admission
and mortality (P < .05) included multiple trauma, vessel trauma, and burns. Other
risk factors included foreign-body, older age, and male gender. CONCLUSIONS:
Primary HN injuries commonly present to emergency rooms in the US. The majority
of HN injuries are non-life threatening and do not require admission to the
hospital or result in death. These data have implications for HN injury
surveillance and may be used to risk-stratify patients who present with injuries
in the acute care setting.
PMID- 25139949
TI - Dissection of the region of Pseudomonas aeruginosa ParA that is important for
dimerization and interactions with its partner ParB.
AB - Pseudomonas aeruginosa ParA belongs to a large subfamily of Walker-type ATPases
acting as partitioning proteins in bacteria. ParA has the ability to both self
associate and interact with its partner ParB. Analysis of the deletion mutants
defined the part of the protein involved in dimerization and interactions with
ParB. Here, a set of ParA alanine substitution mutants in the region between E67
and L85 was created and analysed in vivo and in vitro. All mutants impaired in
dimerization (substitutions at positions M74, H79, Y82 and L84) were also
defective in interactions with ParB, suggesting that ParA-ParB interactions
depend on the ability of ParA to dimerize. Mutants with alanine substitutions at
positions E67, C68, L70, E72, F76, Q83 and L85 were not impaired in dimerization,
but were defective in interactions with ParB. The dimerization interface partly
overlapped the pseudo-hairpin, involved in interactions with ParB. ParA mutant
derivatives tested in vitro showed no defects in ATPase activity. Two parA
alleles (parA84, whose product can neither self-interact nor interact with ParB,
and parA67, whose product is impaired in interactions with ParB, but not in
dimerization) were introduced into the P. aeruginosa chromosome by homologous
gene exchange. Both mutants showed defective separation of ParB foci, but to
different extents. Only PAO1161 parA84 was visibly impaired in terms of
chromosome segregation, growth rate and motility, similar to a parA-null mutant.
PMID- 25139951
TI - Tension pneumocephalus after endoscopic sinus surgery: a technical report of
multiportal endoscopic skull base repair.
PMID- 25139953
TI - Shared mushroom body circuits underlie visual and olfactory memories in
Drosophila.
AB - In nature, animals form memories associating reward or punishment with stimuli
from different sensory modalities, such as smells and colors. It is unclear,
however, how distinct sensory memories are processed in the brain. We established
appetitive and aversive visual learning assays for Drosophila that are comparable
to the widely used olfactory learning assays. These assays share critical
features, such as reinforcing stimuli (sugar reward and electric shock
punishment), and allow direct comparison of the cellular requirements for visual
and olfactory memories. We found that the same subsets of dopamine neurons drive
formation of both sensory memories. Furthermore, distinct yet partially
overlapping subsets of mushroom body intrinsic neurons are required for visual
and olfactory memories. Thus, our results suggest that distinct sensory memories
are processed in a common brain center. Such centralization of related brain
functions is an economical design that avoids the repetition of similar circuit
motifs.
PMID- 25139954
TI - Autism and attention-deficit/hyperactivity disorder among individuals with a
family history of alcohol use disorders.
AB - Recent studies suggest de novo mutations may involve the pathogenesis of autism
and attention-deficit/hyperactivity disorder (ADHD). Based on the evidence that
excessive alcohol consumption may be associated with an increased rate of de novo
mutations in germ cells (sperms or eggs), we examine here whether the risks of
autism and ADHD are increased among individuals with a family history of alcohol
use disorders (AUDs). The standardized incidence ratios (SIRs) of autism and ADHD
among individuals with a biological parental history of AUDs were 1.39 (95% CI
1.34-1.44) and 2.19 (95% CI 2.15-2.23), respectively, compared to individuals
without an affected parent. Among offspring whose parents were diagnosed with
AUDs before their birth, the corresponding risks were 1.46 (95% CI 1.36-1.58) and
2.70 (95% CI 2.59-2.81), respectively. Our study calls for extra surveillance for
children with a family history of AUDs, and further studies examining the
underlying mechanisms are needed.
PMID- 25139955
TI - A suppression hierarchy among competing motor programs drives sequential grooming
in Drosophila.
AB - Motor sequences are formed through the serial execution of different movements,
but how nervous systems implement this process remains largely unknown. We
determined the organizational principles governing how dirty fruit flies groom
their bodies with sequential movements. Using genetically targeted activation of
neural subsets, we drove distinct motor programs that clean individual body
parts. This enabled competition experiments revealing that the motor programs are
organized into a suppression hierarchy; motor programs that occur first suppress
those that occur later. Cleaning one body part reduces the sensory drive to its
motor program, which relieves suppression of the next movement, allowing the
grooming sequence to progress down the hierarchy. A model featuring independently
evoked cleaning movements activated in parallel, but selected serially through
hierarchical suppression, was successful in reproducing the grooming sequence.
This provides the first example of an innate motor sequence implemented by the
prevailing model for generating human action sequences.
PMID- 25139956
TI - The master cell cycle regulator APC-Cdc20 regulates ciliary length and
disassembly of the primary cilium.
AB - The primary cilium has an important role in signaling; defects in structure are
associated with a variety of human diseases. Much of the most basic biology of
this organelle is poorly understood, even basic mechanisms, such as control of
growth and resorption. We show that the activity of the anaphase-promoting
complex (APC), an E3 that regulates the onset of anaphase, destabilizes axonemal
microtubules in the primary cilium. Furthermore, the metaphase APC co-activator,
Cdc20, is specifically recruited to the basal body of primary cilia. Inhibition
of APC-Cdc20 activity increases the ciliary length, while overexpression of Cdc20
suppresses cilium formation. APC-Cdc20 activity is required for the timely
resorption of the cilium after serum stimulation. In addition, APC regulates the
stability of axonemal microtubules through targeting Nek1, the ciliary kinase,
for proteolysis. These data demonstrate a novel function of APC beyond cell cycle
control and implicate critical role of ubiquitin-mediated proteolysis in ciliary
disassembly.
PMID- 25139957
TI - Taking a new look at how flies learn.
AB - Learning based on what a fruit fly sees or what it smells might not involve
distinct parts of the brain, as was previously thought.
PMID- 25139958
TI - What can fruit flies teach us about karate?
AB - Understanding the logic behind how a fruit fly's brain tells it to groom its body
parts in a stereotyped order might help us understand other behaviours that also
involve a series of actions.
PMID- 25139959
TI - A pilot study of quantitative capillary refill time to identify high blood
lactate levels in critically ill patients.
AB - INTRODUCTION: We developed a new device to quantify capillary refill time (CRT)
by applying the pulse oximeter principle, and evaluated the correlation between
quantitative CRT (Q-CRT) and hypoperfusion status, as represented by blood
lactate levels, in critically ill patients. METHODS: A pilot study was undertaken
in the intensive care unit (ICU) in a tertiary emergency medical centre. While
the pulse oxygen saturation sensor was placed on the finger of the patients,
transmitted light intensity (TLI) was measured with a pulse oximeter (OLV-3100;
Nihon Kohden, Tokyo, Japan) before and during compression of the finger. Q-CRT
was defined as the interval from the release of compression to the time when TLI
reached 90% of baseline. RESULTS: Q-CRT was analysed in a total of 57 waveforms
among 23 patients and statistically correlated with lactate levels (Spearman's
rank correlation coefficient, 0.681; p<0.001). The cut-off value of Q-CRT for
predicting a lactate level of >=2.0 mmol/L was 6.81 s (area under the curve (AUC)
(95% CI 1.000 (1.000 to 1.000), p<0.001), and the value for predicting a lactate
level of >=4.0 mmol/L was 7.27 s (AUC=0.989 (95% CI 0.954 to 1.000), p<0.001).
CONCLUSIONS: Q-CRT correlated with blood lactate levels in this pilot study. The
most useful threshold for Q-CRT was ~6-8 s. Further study is needed to
investigate the potential role of this modality as a non-invasive predictor of
hypoperfusion in the emergency department, ICU and operating room settings.
PMID- 25139960
TI - Diabetes and ischemic heart disease: double jeopardy with regard to depressive
mood and reduced quality of life.
AB - The aim of this study was to test i) whether patients having diabetes and
ischemic heart disease (IHD), i.e., patients suffering from two chronic diseases,
demonstrate a higher degree of chronic stress when compared with patients
suffering from IHD alone, and ii) whether suffering from the two chronic diseases
results in an elevation in specific elements of the chronic stress concept. A
total of 361 participants with IHD were included, of whom 47 suffered from
concomitant diabetes. Stress was measured by pressure pain sensitivity (PPS) and
by the following questionnaires: the Major Depression Inventory (MDI), the SF-36
Quality of Life questionnaire (SF-36 QOL), the WHO-5 Well-being Index, and the
clinical stress signs (CSSs) scale. Participants with diabetes and IHD had a
higher MDI score, a lower SF-36 physical component summary score, and a lower
score of several sub-measurements of the SF-36 mental component score when
compared with patients with IHD without diabetes. No significant differences were
observed regarding stress measured by the PPS measure, the WHO-5 Well-being
Index, or the number of CSSs. In conclusion, the combination of diabetes and IHD
seems to be associated with increased depressive symptoms, lower overall physical
QOL, and reduced mental QOL on several sub-elements of the questionnaire. This
should be recognized in the management of patients with double diagnoses.
PMID- 25139961
TI - High usage of topical fusidic acid and rapid clonal expansion of fusidic acid
resistant Staphylococcus aureus: a cautionary tale.
AB - Our aim was to assess national prescribing trends and determine longitudinal
resistance patterns for topical antimicrobials in New Zealand. We observed a
dramatic increase in fusidic acid (FA) resistance, and clonal expansion of FA
resistant Staphylococcus aureus. This increase was concurrent with a significant
national increase in topical FA dispensing.
PMID- 25139962
TI - Prevalence and predictors for homo- and heterosubtypic antibodies against
influenza a virus.
AB - BACKGROUND: The effectiveness of trivalent influenza vaccination has been
confirmed in several studies. To date, it is not known whether repeated exposure
and vaccination to influenza promote production of cross-reactive antibodies.
Furthermore, how strains encountered earlier in life imprint the immune response
is currently poorly understood. METHODS: To determine the prevalence for human
homo- and heterosubtypic antibody responses, we scrutinized serum samples from
305 healthy volunteers for hemagglutinin-binding and -neutralizing antibodies
against several strains and subtypes of influenza A. Statistical analyses were
then performed to establish the association of measured values with potential
predictors. RESULTS: It was found that vaccination not only promoted higher
binding and neutralizing antibody titers to homosubtypic influenza isolates but
also increased heterosubtypic human immune responses. Both binding and
neutralizing antibody titers in relation with age of the donors mirrored the
course of the different influenza strain circulation during the last century.
Advanced age appeared to be of advantage for both binding and neutralizing titers
to most subtypes. In contrast, the first virus subtype encountered was found to
imprint to some degree subsequent antibody responses. Antibodies to recent
strains, however, primarily seemed to be promoted by vaccination. CONCLUSIONS: We
provide evidence that vaccinations stimulate both homo- and heterosubtypic immune
responses in young and middle-aged as well as more senior individuals. Our
analyses suggest that influenza vaccinations not only prevent infection against
currently circulating strains but can also stimulate broader humoral immune
responses that potentially attenuate infections with zoonotic or antigenically
shifted strains.
PMID- 25139964
TI - Does HIV remain a risk factor for achieving sustained virologic response under
direct acting antiviral-based modern hepatitis C virus therapy?
PMID- 25139963
TI - Telaprevir for HIV/hepatitis C virus-coinfected patients failing treatment with
pegylated interferon/ribavirin (ANRS HC26 TelapreVIH): an open-label, single-arm,
phase 2 trial.
AB - BACKGROUND: Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV)
results in poor sustained virological response (SVR) rates in human
immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. There
are limited data regarding the use of telaprevir plus peg-IFN/RBV in this
population. METHODS: HIV type 1-infected patients who previously failed >=12
weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single
arm, phase 2 trial. Patients with cirrhosis and previous null response were
excluded. Authorized antiretrovirals were tenofovir, emtricitabine, efavirenz,
atazanavir, and raltegravir. All patients received peg-IFN alfa-2a (180 ug/week)
plus RBV (1000-1200 mg/day) for 4 weeks, followed by telaprevir (750 mg or 1125
mg every 8 hours with efavirenz) plus peg-IFN/RBV for 12 weeks and peg-IFN/RBV
for 32-56 weeks according to virological response at week 8. The primary endpoint
was the SVR rate at 24 weeks after the end of treatment (SVR24). RESULTS: Sixty
nine patients started treatment; SVR24 was achieved in 55 (80% [95% confidence
interval, 68%-88%). SVR24 was not influenced by baseline fibrosis stage, IL28B
genotype, antiretroviral regimen, HCV subtype, CD4 cell count, previous response
to HCV treatment, HCV RNA level, or HCV RNA decline at week 4. HCV treatment was
discontinued for adverse events (AEs) in 20% of patients, including cutaneous
(4%), psychiatric (4%), hematological (6%), and other AEs (6%). Peg-IFN or RBV
dose reduction was required in 23% and 43% of patients, respectively. Seventy
percent of patients required erythropoietin, blood transfusions, or RBV dose
reduction for anemia. Two patients died during the study. No HIV breakthrough was
observed. CONCLUSIONS: Despite a high discontinuation rate related to toxicity, a
substantial proportion of treatment-experienced HIV-coinfected patients achieved
SVR24 with a telaprevir-based regimen. Clinical Trials Registration. NCT01332955.
PMID- 25139965
TI - Reply to Antinori et al.
PMID- 25139966
TI - Diagnosis of central nervous system mycoses in solid organ transplant recipients.
PMID- 25139967
TI - Editorial commentary: Changing epidemiology of influenza B virus.
PMID- 25139968
TI - Uniform research case definition criteria differentiate tuberculous and bacterial
meningitis in children.
AB - BACKGROUND: Tuberculous meningitis (TBM) research is hampered by low numbers of
microbiologically confirmed TBM cases and the fact that they may represent a
select part of the disease spectrum. A uniform TBM research case definition was
developed to address these limitations, but its ability to differentiate TBM from
bacterial meningitis has not been evaluated. METHODS: We assessed all children
treated for TBM from 1985 to 2005 at Tygerberg Children's Hospital, Cape Town,
South Africa. For comparative purposes, a group of children with culture
confirmed bacterial meningitis, diagnosed between 2003 and 2009, was identified
from the National Health Laboratory Service database. The performance of the
proposed case definition was evaluated in culture-confirmed TBM and bacterial
meningitis cases. RESULTS: Of 554 children treated for TBM, 66 (11.9%) were
classified as "definite TBM," 408 (73.6%) as "probable TBM," and 72 (13.0%) as
"possible TBM." "Probable TBM" criteria identified culture-confirmed TBM with a
sensitivity of 86% and specificity of 100%; sensitivity was increased but
specificity reduced when using "possible TBM" criteria (sensitivity 100%,
specificity 56%). CONCLUSIONS: "Probable TBM" criteria accurately differentiated
TBM from bacterial meningitis and could be considered for use in clinical trials;
reduced sensitivity in children with early TBM (stage 1 disease) remains a
concern.
PMID- 25139970
TI - News feature: How to light a cosmic candle.
PMID- 25139969
TI - Impact of influenza B lineage-level mismatch between trivalent seasonal influenza
vaccines and circulating viruses, 1999-2012.
AB - BACKGROUND: Influenza B virus strains in trivalent influenza vaccines are
frequently mismatched to the circulating B strains, but the population-level
impact of such mismatches is unknown. We assessed the impact of vaccine mismatch
on the epidemiology of influenza B during 12 recent seasonal outbreaks of
influenza in Finland. METHODS: We analyzed all available nationwide data on
virologically confirmed influenza infections in all age groups in Finland between
1 July 1999 and 30 June 2012, with the exclusion of the pandemic season of 2009
2010. We derived data on influenza infections and the circulation of different
lineages of B viruses during each season from the Infectious Diseases Register
and the National Influenza Center, National Institute for Health and Welfare,
Finland. RESULTS: A total of 34 788 cases of influenza were recorded. Influenza A
accounted for 74.0% and influenza B for 26.0% of all typed viruses. Throughout
the 12 seasons, we estimated that 41.7% (3750 of 8993) of all influenza B
infections were caused by viruses representing the other genetic lineage than the
one in the vaccine. Altogether, opposite-lineage influenza B viruses accounted
for 10.8% of all influenza infections in the population, the proportion being
highest (16.8%) in children aged 10-14 years and lowest (2.6%) in persons aged
>=70 years. CONCLUSIONS: The population-level impact of lineage-level mismatch
between the vaccine and circulating strains of influenza B viruses is
substantial, especially among children and adolescents. The results provide
strong support for the inclusion of both influenza B lineages in seasonal
influenza vaccines.
PMID- 25139972
TI - Cleaning up the record on the maximal information coefficient and equitability.
PMID- 25139973
TI - A pending issue: an analysis of health promotion research in Latin America.
PMID- 25139980
TI - For bats and dolphins, hearing gene prestin adapted for echolocation.
PMID- 25139979
TI - Effect of High-Dose Cysteine Supplementation on Erythrocyte Glutathione: A Double
Blinded, Randomized Placebo-Controlled Pilot Study in Critically Ill Neonates.
AB - BACKGROUND: This study's objective was to determine if parenteral cysteine when
compared with isonitrogenous noncysteine supplementation increases erythrocyte
reduced glutathione (GSH) in neonates at high risk for inflammatory injury.
MATERIAL AND METHODS: Neonates with a score for neonatal acute physiology >10
requiring mechanical ventilation and parenteral nutrition (PN) were randomized in
a double-blinded, placebo-controlled study to receive parenteral cysteine-HCl
(CYS group) or additional PN amino acids (ISO group) at 121 mg/kg/d for >=7 days.
A 6-hour [(13)C2] glycine IV infusion was administered at study week 1 to
determine the fractional synthetic rate of GSH (FSR-GSH). RESULTS: Baseline
characteristics were similar between the CYS (n = 17) and ISO groups (n = 21).
Erythrocyte GSH and total glutathione concentrations, GSH:oxidized GSH (GSSG),
and FSR-GSH after treatment were not different between groups. However, the CYS
group had a larger individual positive change in GSH and total glutathione
(infusion day - baseline) compared with the ISO group (P = .02 for each). After
adjusting for treatment, a lower enrollment weight and rate of red blood cell
transfusion were associated with a decreased change in total glutathione and GSH
(P < .05 for each). CONCLUSION: When compared with isonitrogenous noncysteine
supplementation, high-dose cysteine supplementation for at least 1 week in
critically ill neonates resulted in a larger and more positive individual change
in GSH. Smaller infants and those who received transfused blood demonstrated less
effective change in GSH with cysteine supplementation. The benefit of cysteine
remains promising and deserves further investigation.
PMID- 25139985
TI - Experimental basis for a new allosteric model for multisubunit proteins.
AB - Monod, Wyman, and Changeux (MWC) explained allostery in multisubunit proteins
with a widely applied theoretical model in which binding of small molecules, so
called allosteric effectors, affects reactivity by altering the equilibrium
between more reactive (R) and less reactive (T) quaternary structures. In their
model, each quaternary structure has a single reactivity. Here, we use silica
gels to trap protein conformations and a new kind of laser photolysis experiment
to show that hemoglobin, the paradigm of allostery, exhibits two ligand binding
phases with the same fast and slow rates in both R and T quaternary structures.
Allosteric effectors change the fraction of each phase but not the rates. These
surprising results are readily explained by the simplest possible extension of
the MWC model to include a preequilibrium between two tertiary conformations that
have the same functional properties within each quaternary structure. They also
have important implications for the long-standing question of a structural
explanation for the difference in hemoglobin oxygen affinity of the two
quaternary structures.
PMID- 25139986
TI - Phospholipase A2 regulates eicosanoid class switching during inflammasome
activation.
AB - Initiation and resolution of inflammation are considered to be tightly connected
processes. Lipoxins (LX) are proresolution lipid mediators that inhibit
phlogistic neutrophil recruitment and promote wound-healing macrophage
recruitment in humans via potent and specific signaling through the LXA4 receptor
(ALX). One model of lipoxin biosynthesis involves sequential metabolism of
arachidonic acid by two cell types expressing a combined transcellular metabolon.
It is currently unclear how lipoxins are efficiently formed from precursors or if
they are directly generated after receptor-mediated inflammatory commitment.
Here, we provide evidence for a pathway by which lipoxins are generated in
macrophages as a consequence of sequential activation of toll-like receptor 4
(TLR4), a receptor for endotoxin, and P2X7, a purinergic receptor for
extracellular ATP. Initial activation of TLR4 results in accumulation of the
cyclooxygenase-2-derived lipoxin precursor 15-hydroxyeicosatetraenoic acid (15
HETE) in esterified form within membrane phospholipids, which can be enhanced by
aspirin (ASA) treatment. Subsequent activation of P2X7 results in efficient
hydrolysis of 15-HETE from membrane phospholipids by group IVA cytosolic
phospholipase A2, and its conversion to bioactive lipoxins by 5-lipoxygenase. Our
results demonstrate how a single immune cell can store a proresolving lipid
precursor and then release it for bioactive maturation and secretion,
conceptually similar to the production and inflammasome-dependent maturation of
the proinflammatory IL-1 family cytokines. These findings provide evidence for
receptor-specific and combinatorial control of pro- and anti-inflammatory
eicosanoid biosynthesis, and potential avenues to modulate inflammatory indices
without inhibiting downstream eicosanoid pathways.
PMID- 25139987
TI - Efficient utilization of complex N-linked glycans is a selective advantage for
Bacteroides fragilis in extraintestinal infections.
AB - Bacteroides fragilis is the most common anaerobe isolated from clinical
infections, and in this report we demonstrate a characteristic of the species
that is critical to their success as an opportunistic pathogen. Among the
Bacteroides spp. in the gut, B. fragilis has the unique ability of efficiently
harvesting complex N-linked glycans from the glycoproteins common to serum and
serous fluid. This activity is mediated by an outer membrane protein complex
designated as Don. Using the abundant serum glycoprotein transferrin as a model,
it has been shown that B. fragilis alone can rapidly and efficiently
deglycosylate this protein in vitro and that transferrin glycans can provide the
sole source of carbon and energy for growth in defined media. We then showed that
transferrin deglycosylation occurs in vivo when B. fragilis is propagated in the
rat tissue cage model of extraintestinal growth, and that this ability provides a
competitive advantage in vivo over strains lacking the don locus.
PMID- 25139988
TI - Assembly and dynamics of the autophagy-initiating Atg1 complex.
AB - The autophagy-related 1 (Atg1) complex of Saccharomyces cerevisiae has a central
role in the initiation of autophagy following starvation and TORC1 inactivation.
The complex consists of the protein kinase Atg1, the TORC1 substrate Atg13, and
the trimeric Atg17-Atg31-Atg29 scaffolding subcomplex. Autophagy is triggered
when Atg1 and Atg13 assemble with the trimeric scaffold. Here we show by hydrogen
deuterium exchange coupled to mass spectrometry that the mutually interacting
Atg1 early autophagy targeting/tethering domain and the Atg13 central domain are
highly dynamic in isolation but together form a stable complex with ~ 100-nM
affinity. The Atg1-Atg13 complex in turn binds as a unit to the Atg17-Atg31-Atg29
scaffold with ~ 10-MUM affinity via Atg13. The resulting complex consists
primarily of a dimer of pentamers in solution. These results lead to a model for
autophagy initiation in which Atg1 and Atg13 are tightly associated with one
another and assemble transiently into the pentameric Atg1 complex during
starvation.
PMID- 25139989
TI - Bioinformatic analysis reveals a pattern of STAT3-associated gene expression
specific to basal-like breast cancers in human tumors.
AB - Signal transducer and activator of transcription 3 (STAT3), a latent
transcription factor associated with inflammatory signaling and innate and
adaptive immune responses, is known to be aberrantly activated in a wide variety
of cancers. In vitro analysis of STAT3 in human cancer cell lines has elucidated
a number of specific targets associated with poor prognosis in breast cancer.
However, to date, no comparison of cancer subtype and gene expression associated
with STAT3 signaling in human patients has been reported. In silico analysis of
human breast cancer microarray and reverse-phase protein array data was performed
to identify expression patterns associated with STAT3 in basal-like and luminal
breast cancers. Results indicate clearly identifiable STAT3-regulated signatures
common to basal-like breast cancers but not to luminal A or luminal B cancers.
Furthermore, these differentially expressed genes are associated with immune
signaling and inflammation, a known phenotype of basal-like cancers. These
findings demonstrate a distinct role for STAT3 signaling in basal breast cancers,
and underscore the importance of considering subtype-specific molecular pathways
that contribute to tissue-specific cancers.
PMID- 25139990
TI - Immunolocalization of skeletal matrix proteins in tissue and mineral of the coral
Stylophora pistillata.
AB - The precipitation and assembly of calcium carbonate skeletons by stony corals is
a precisely controlled process regulated by the secretion of an ECM. Recently, it
has been reported that the proteome of the skeletal organic matrix (SOM) contains
a group of coral acid-rich proteins as well as an assemblage of adhesion and
structural proteins, which together, create a framework for the precipitation of
aragonite. To date, we are aware of no report that has investigated the
localization of individual SOM proteins in the skeleton. In particular, no data
are available on the ultrastructural mapping of these proteins in the
calcification site or the skeleton. This information is crucial to assessing the
role of these proteins in biomineralization. Immunological techniques represent a
valuable approach to localize a single component within a calcified skeleton. By
using immunogold labeling and immunohistochemical assays, here we show the
spatial arrangement of key matrix proteins in tissue and skeleton of the common
zooxanthellate coral, Stylophora pistillata. To our knowledge, our results reveal
for the first time that, at the nanoscale, skeletal proteins are embedded within
the aragonite crystals in a highly ordered arrangement consistent with a diel
calcification pattern. In the tissue, these proteins are not restricted to the
calcifying epithelium, suggesting that they also play other roles in the coral's
metabolic pathways.
PMID- 25139991
TI - Endothelial cell FGF signaling is required for injury response but not for
vascular homeostasis.
AB - Endothelial cells (ECs) express fibroblast growth factor receptors (FGFRs) and
are exquisitely sensitive to FGF signals. However, whether the EC or another
vascular cell type requires FGF signaling during development, homeostasis, and
response to injury is not known. Here, we show that Flk1-Cre or Tie2-Cre mediated
deletion of FGFR1 and FGFR2 (Fgfr1/2(Flk1-Cre) or Fgfr1/2(Tie2-Cre) mice), which
results in deletion in endothelial and hematopoietic cells, is compatible with
normal embryonic development. As adults, Fgfr1/2(Flk1-Cre) mice maintain normal
blood pressure and vascular reactivity and integrity under homeostatic
conditions. However, neovascularization after skin or eye injury was
significantly impaired in both Fgfr1/2(Flk1-Cre) and Fgfr1/2(Tie2-Cre) mice,
independent of either hematopoietic cell loss of FGFR1/2 or vascular endothelial
growth factor receptor 2 (Vegfr2) haploinsufficiency. Also, impaired
neovascularization was associated with delayed cutaneous wound healing. These
findings reveal a key requirement for cell-autonomous EC FGFR signaling in injury
induced angiogenesis, but not for vascular homeostasis, identifying the EC FGFR
signaling pathway as a target for diseases associated with aberrant vascular
proliferation, such as age-related macular degeneration, and for modulating wound
healing without the potential toxicity associated with direct manipulation of
systemic FGF or VEGF activity.
PMID- 25139992
TI - Interlamellar CA1 network in the hippocampus.
AB - To understand the cellular basis of learning and memory, the neurophysiology of
the hippocampus has been largely examined in thin transverse slice preparations.
However, the synaptic architecture along the longitudinal septo-temporal axis
perpendicular to the transverse projections in CA1 is largely unknown, despite
its potential significance for understanding the information processing carried
out by the hippocampus. Here, using a battery of powerful techniques, including
3D digital holography and focal glutamate uncaging, voltage-sensitive dye, two
photon imaging, electrophysiology, and immunohistochemistry, we show that CA1
pyramidal neurons are connected to one another in an associational and well
organized fashion along the longitudinal axis of the hippocampus. Such CA1
longitudinal connections mediate reliable signal transfer among the pyramidal
cells and express significant synaptic plasticity. These results illustrate a
need to reconceptualize hippocampal CA1 network function to include not only
processing in the transverse plane, but also operations made possible by the
longitudinal network. Our data will thus provide an essential basis for future
computational modeling studies on information processing operations carried out
in the full 3D hippocampal network that underlies its complex cognitive
functions.
PMID- 25139993
TI - Targeted gene knockout in chickens mediated by TALENs.
AB - Genetically modified animals are used for industrial applications as well as
scientific research, and studies on these animals contribute to a better
understanding of biological mechanisms. Gene targeting techniques have been
developed to edit specific gene loci in the genome, but the conventional strategy
of homologous recombination with a gene-targeted vector has low efficiency and
many technical complications. Here, we generated specific gene knockout chickens
through the use of transcription activator-like effector nuclease (TALEN)
mediated gene targeting. In this study, we accomplished targeted knockout of the
ovalbumin (OV) gene in the chicken primordial germ cells, and OV gene mutant
offspring were generated through test-cross analysis. TALENs successfully induced
nucleotide deletion mutations of ORF shifts, resulting in loss of chicken OV gene
function. Our results demonstrate that the TALEN technique used in the chicken
primordial germ cell line is a powerful strategy to create specific genome-edited
chickens safely for practical applications.
PMID- 25139994
TI - Roles of cGMP-dependent protein kinase I (cGKI) and PDE5 in the regulation of Ang
II-induced cardiac hypertrophy and fibrosis.
AB - Conflicting results have been reported for the roles of cGMP and cGMP-dependent
protein kinase I (cGKI) in various pathological conditions leading to cardiac
hypertrophy and fibrosis. A cardioprotective effect of cGMP/cGKI has been
reported in whole animals and isolated cardiomyocytes, but recent evidence from a
mouse model expressing cGKIbeta only in smooth muscle (betaRM) but not in
cardiomyocytes, endothelial cells, or fibroblasts has forced a reevaluation of
the requirement for cGKI activity in the cardiomyocyte antihypertrophic effects
of cGMP. In particular, betaRM mice developed the same hypertrophy as WT controls
when subjected to thoracic aortic constriction or isoproterenol infusion. Here,
we challenged betaRM and WT (Ctr) littermate control mice with angiotensin II
(AII) infusion (7 d; 2 mg ? kg(-1) ? d(-1)) to induce hypertrophy. Both genotypes
developed cardiac hypertrophy, which was more pronounced in Ctr animals.
Cardiomyocyte size and interstitial fibrosis were increased equally in both
genotypes. Addition of sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, in the
drinking water had a small effect in reducing myocyte hypertrophy in WT mice and
no effect in betaRM mice. However, sildenafil substantially blocked the increase
in collagen I, fibronectin 1, TGFbeta, and CTGF mRNA in Ctr but not in betaRM
hearts. These data indicate that, for the initial phase of AII-induced cardiac
hypertrophy, lack of cardiomyocyte cGKI activity does not worsen hypertrophic
growth. However, expression of cGKI in one or more cell types other than smooth
muscle is necessary to allow the antifibrotic effect of sildenafil.
PMID- 25139995
TI - Reconstruction and minimal gene requirements for the alternative iron-only
nitrogenase in Escherichia coli.
AB - All diazotrophic organisms sequenced to date encode a molybdenum-dependent
nitrogenase, but some also have alternative nitrogenases that are dependent on
either vanadium (VFe) or iron only (FeFe) for activity. In Azotobacter
vinelandii, expression of the three different types of nitrogenase is regulated
in response to metal availability. The majority of genes required for nitrogen
fixation in this organism are encoded in the nitrogen fixation (nif) gene
clusters, whereas genes specific for vanadium- or iron-dependent diazotophy are
encoded by the vanadium nitrogen fixation (vnf) and alternative nitrogen fixation
(anf) genes, respectively. Due to the complexities of metal-dependent regulation
and gene redundancy in A. vinelandii, it has been difficult to determine the
precise genetic requirements for alternative nitrogen fixation. In this study, we
have used Escherichia coli as a chassis to build an artificial iron-only (Anf)
nitrogenase system composed of defined anf and nif genes. Using this system, we
demonstrate that the pathway for biosynthesis of the iron-only cofactor (FeFe-co)
is likely to be simpler than the pathway for biosynthesis of the molybdenum
dependent cofactor (FeMo-co) equivalent. A number of genes considered to be
essential for nitrogen fixation by FeFe nitrogenase, including nifM, vnfEN, and
anfOR, are not required for the artificial Anf system in E. coli. This finding
has enabled us to engineer a minimal FeFe nitrogenase system comprising the
structural anfHDGK genes and the nifBUSV genes required for metallocluster
biosynthesis, with nifF and nifJ providing electron transport to the alternative
nitrogenase. This minimal Anf system has potential implications for engineering
diazotrophy in eukaryotes, particularly in compartments (e.g., organelles) where
molybdenum may be limiting.
PMID- 25139996
TI - Nedd9 restrains renal cystogenesis in Pkd1-/- mice.
AB - Mutations inactivating the cilia-localized Pkd1 protein result in autosomal
dominant polycystic kidney disease (ADPKD), a serious inherited syndrome
affecting ~ 1 in 500 people, in which accumulation of renal cysts eventually
destroys kidney function. Severity of ADPKD varies throughout the population, for
reasons thought to involve differences both in intragenic Pkd1 mutations and in
modifier alleles. The scaffolding protein NEDD9, commonly dysregulated during
cancer progression, interacts with Aurora-A (AURKA) kinase to control ciliary
resorption, and with Src and other partners to influence proliferative signaling
pathways often activated in ADPKD. We here demonstrate Nedd9 expression is
deregulated in human ADPKD and a mouse ADPKD model. Although genetic ablation of
Nedd9 does not independently influence cystogenesis, constitutive absence of
Nedd9 strongly promotes cyst formation in the tamoxifen-inducible
Pkd1fl/fl;Cre/Esr1(+) mouse model of ADPKD. This cystogenic effect is associated
with striking morphological defects in the cilia of Pkd1(-/-);Nedd9(-/-) mice,
associated with specific loss of ciliary localization of adenylase cyclase III in
the doubly mutant genotype. Ciliary phenotypes imply a failure of Aurora-A
activation: Compatible with this idea, Pkd1(-/-);Nedd9(-/-) mice had ciliary
resorption defects, and treatment of Pkd1(-/-) mice with a clinical Aurora-A
kinase inhibitor exacerbated cystogenesis. In addition, activation of the ADPKD
associated signaling effectors Src, Erk, and the mTOR effector S6 was enhanced,
and Ca(2+) response to external stimuli was reduced, in Pkd1(-/-);Nedd9(-/-)
versus Pkd1(-/-) mice. Together, these results indicated an important modifier
action of Nedd9 on ADPKD pathogenesis involving failure to activate Aurora-A.
PMID- 25139997
TI - Refilling drug delivery depots through the blood.
AB - Local drug delivery depots have significant clinical utility, but there is
currently no noninvasive technique to refill these systems once their payload is
exhausted. Inspired by the ability of nanotherapeutics to target specific
tissues, we hypothesized that blood-borne drug payloads could be modified to home
to and refill hydrogel drug delivery systems. To address this possibility,
hydrogels were modified with oligodeoxynucleotides (ODNs) that provide a target
for drug payloads in the form of free alginate strands carrying complementary
ODNs. Coupling ODNs to alginate strands led to specific binding to complementary
ODN-carrying alginate gels in vitro and to injected gels in vivo. When coupled to
a drug payload, sequence-targeted refilling of a delivery depot consisting of
intratumor hydrogels completely abrogated tumor growth. These results suggest a
new paradigm for nanotherapeutic drug delivery, and this concept is expected to
have applications in refilling drug depots in cancer therapy, wound healing, and
drug-eluting vascular grafts and stents.
PMID- 25139999
TI - Axl kinase as a key target for oncology: focus on small molecule inhibitors.
AB - Receptor tyrosine kinases (RTK) are transmembrane receptors that regulate signal
transduction in cells. As a member of the TAM (Tyro-3, Axl, Mer) RTK subfamily,
Axl regulates key processes such as cell growth, migration, aggregation, and
apoptosis through several pathways. Its overexpression/overactivation has been
underlined in several conditions, especially cancers, and in both chemotherapy
and targeted therapy sensitivity loss. In this review, we propose to highlight
the therapeutic implication of Axl, starting with the pathways it regulates,
validating its interest as a therapeutic target, and defining the tools available
to develop strategies for its inhibition. We especially focus on small molecule
inhibitors, their structure, inhibition profile, and development stages.
PMID- 25139998
TI - Annexin 2-CXCL12 interactions regulate metastatic cell targeting and growth in
the bone marrow.
AB - Annexin 2 (ANXA2) plays a critical role in hematopoietic stem cell (HSC)
localization to the marrow niche. In part, ANXA2 supports HSCs by serving as an
anchor for stromal-derived factor-1 (CXCL12/SDF-1). Recently, it was demonstrated
that prostate cancer cells, like HSCs, use ANXA2 to establish metastases in
marrow. The present study determined the capacity of ANXA2 expression by bone
marrow stromal cells (BMSC) to facilitate tumor recruitment and growth through
ANXA2-CXCL12 interactions. Significantly more CXCL12 was expressed by BMSC(Anxa2)
(+/+) than by BMSC(Anxa2) (-/-) resulting in more prostate cancer cells migrating
and binding to BMSC(Anxa2) (+/+) than BMSC(Anxa2) (-/-), and these activities
were reduced when CXCL12 interactions were blocked. To further confirm that BMSC
signaling through ANXA2-CXCL12 plays a critical role in tumor growth,
immunocompromised SCID mice were subcutaneously implanted with human prostate
cancer cells mixed with BMSC(Anxa2) (+/+) or BMSC(Anxa2) (-/-). Significantly
larger tumors grew in the mice when the tumors were established with BMSC(Anxa2)
(+/+) compared with the tumors established with BMSC(Anxa2) (-/-). In addition,
fewer prostate cancer cells underwent apoptosis when cocultured with BMSC(Anxa2)
(+/+) compared with BMSC(Anxa2) (-/-), and similar results were obtained in
tumors grown in vivo. Finally, significantly more vascular structures were
observed in the tumors established with the BMSC(Anxa2) (+/+) compared with the
tumors established with BMSC(Anxa2) (-/-). Thus, ANXA2-CXCL12 interactions play a
crucial role in the recruitment, growth, and survival of prostate cancer cells in
the marrow. IMPLICATIONS: The tumor microenvironment interaction between ANXA2
CXCL12 is critical for metastatic phenotypes and may impact chemotherapeutic
potential.
PMID- 25140000
TI - Epidermal growth factor-like domain 7 predicts response to first-line
chemotherapy and bevacizumab in patients with metastatic colorectal cancer.
AB - The number of approved antiangiogenic drugs is constantly growing and emphasizes
the need for predictive biomarkers. The aim of this study was to analyze the
predictive value of epidermal growth factor-like domain 7 (EGFL7) and microRNA
126 (miR126) to first-line chemotherapy combined with bevacizumab, in patients
with metastatic colorectal cancer (mCRC). A total of 158 patients from two
different, but comparable, cohorts were included. Analyses were performed on
tumor tissue from the primary tumor either based on a whole-tumor resection or an
endoscopic biopsy. EGFL7 was analyzed by immunohistochemistry (IHC) and miR126 by
in situ hybridization (ISH). Both biomarkers were quantified by image-guided
analyses. Endpoints were response rate (RR) and progression-free survival (PFS).
The EGFL7 vessel area (VA) in tumor resections was closely related to treatment
response with a median EGFL7 VA in responding patients of 4 [95% confidence
interval (CI), 4-6] compared with 8.5 (95% CI, 7-11) in nonresponders, P =
0.0008. This difference translated into a borderline significant difference in
PFS (P = 0.06). Furthermore, a significant relationship between high EGFL7 VA and
KRAS mutation was detected (P = 0.049). The results showed no significant
relationship between the miR126 VA and the clinical endpoints. Our study suggests
a predictive value of EGFL7 in regard to first-line chemotherapy and bevacizumab
in patients with mCRC and supports the mechanism of a dual blocking of the
vascular endothelial growth factor-A and EGFL7 axis in this setting.
PMID- 25140001
TI - The effect of conditioned medium derived from human placental multipotent
mesenchymal stromal cells on neutrophils: possible implications for placental
infection.
AB - The role of human placental multipotent mesenchymal stromal cells (hPMSCs) in
placental inflammation is unknown. We hypothesize that hPMSCs are involved in the
early phases of placental infection. hPMSCs were isolated from term placentas and
neutrophils from peripheral blood. The expression of toll-like receptors (TLRs)
and cytokines by hPMSCs was determined by RT-PCR, flow cytometry and enzyme
linked immunosorbent assay. The effect of conditioned medium of hPMSCs with or
without lipopolysaccharide (LPS) pretreatment on neutrophil functions: migration,
apoptosis and production of reactive oxygen species (ROS) was assessed by flow
cytometry and western blot. hPMSCs expressed TLR1, TLR3, TLR4, TLR6, TLR7 and
TLR9. LPS stimulation increased the expression of TLR4 and the production of IL-6
and IL-8 by hPMSCs. Neutrophils exhibited chemotaxis to hPMSC-conditioned medium,
which was inhibited by IL-8 depletion. Neutrophil CD11b activation was promoted
by hPMSC-conditioned medium, which was further enhanced in media from hPMSCs
pretreated with LPS. hPMSC-conditioned medium reduced neutrophil ROS production.
Neutrophil phagocytosis was increased by LPS alone but not by hPMSC-conditioned
medium with or without LPS stimulation. hPMSC-conditioned medium induced STAT3
activation in neutrophils, which was inhibited by neutralizing antibody to IL-6.
hPMSC-conditioned medium rescued neutrophils from apoptosis, but this effect was
significantly reduced in conditioned medium of hPMSCs with LPS pretreatment.
Depletion of IL-6 from the conditioned medium further inhibited the anti
apoptotic effect on neutrophils. Our results demonstrate that hPMSCs can interact
with peripheral blood neutrophils in response to inflammatory signals of the
placenta. Cytokines produced by hPMSCs can induce neutrophil chemotaxis and
reduce neutrophil apoptosis.
PMID- 25140002
TI - Clemizole hydrochloride is a novel and potent inhibitor of transient receptor
potential channel TRPC5.
AB - Canonical transient receptor potential channel 5 (TRPC5) is a nonselective,
Ca(2+)-permeable cation channel that belongs to the large family of transient
receptor potential channels. It is predominantly found in the central nervous
system with a high expression density in the hippocampus, the amygdala, and the
frontal cortex. Several studies confirm that TRPC5 channels are implicated in the
regulation of neurite length and growth cone morphology. We identified clemizole
as a novel inhibitor of TRPC5 channels. Clemizole efficiently blocks TRPC5
currents and Ca(2+) entry in the low micromolar range (IC50 = 1.0-1.3 uM), as
determined by fluorometric intracellular free Ca(2+) concentration ([Ca(2+)]i)
measurements and patch-clamp recordings. Clemizole blocks TRPC5 currents
irrespectively of the mode of activation, for example, stimulation of G protein
coupled receptors, hypo-osmotic buffer conditions, or by the direct activator
riluzole. Electrophysiological whole-cell recordings revealed that the block was
mostly reversible. Moreover, clemizole was still effective in blocking TRPC5
single channels in excised inside-out membrane patches, hinting to a direct block
of TRPC5 by clemizole. Based on fluorometric [Ca(2+)]i measurements, clemizole
exhibits a sixfold selectivity for TRPC5 over TRPC4beta (IC50 = 6.4 uM), the
closest structural relative of TRPC5, and an almost 10-fold selectivity over
TRPC3 (IC50 = 9.1 uM) and TRPC6 (IC50 = 11.3 uM). TRPM3 and M8 as well as TRPV1,
V2, V3, and V4 channels were only weakly affected by markedly higher clemizole
concentrations. Clemizole was not only effective in blocking heterologously
expressed TRPC5 homomers but also TRPC1:TRPC5 heteromers as well as native TRPC5
like currents in the U-87 glioblastoma cell line.
PMID- 25140004
TI - Novel oral anticoagulants: too good to be true?
PMID- 25140003
TI - Robust hydrolysis of prostaglandin glycerol esters by human monoacylglycerol
lipase (MAGL).
AB - The primary route of inactivation of the endocannabinoid 2-arachidonoylglycerol
in the central nervous system is through enzymatic hydrolysis, mainly carried out
by monoacylglycerol lipase (MAGL), along with a small contribution by the
alpha/beta-hydrolase domain (ABHD) proteins ABHD6 and ABHD12. Recent
methodological progress allowing kinetic monitoring of glycerol liberation has
facilitated substrate profiling of the human endocannabinoid hydrolases, and
these studies have revealed that the three enzymes have distinct monoacylglycerol
substrate and isomer preferences. Here, we have extended this substrate profiling
to cover four prostaglandin glycerol esters, namely, 15-deoxy-Delta(12,14)
prostaglandin J2-2-glycerol (15d-PGJ2-G), PGD2-G, PGE2-G, and PGF2 alpha-G. We
found that the three enzymes hydrolyzed the tested substrates, albeit with
distinct rates and preferences. Although human ABHD12 (hABHD12) showed only
marginal activity toward PGE2-G, hABHD6 preferentially hydrolyzed PGD2-G, and
human MAGL (hMAGL) robustly hydrolyzed all four. This was particularly intriguing
for MAGL activity toward 15d-PGJ2-G whose hydrolysis rate rivaled that of the
best monoacylglycerol substrates. Molecular modeling studies combined with
kinetic analysis supported favorable interaction with the hMAGL active site. Long
and short MAGL isoforms shared a similar substrate profile, and hMAGL hydrolyzed
15d-PGJ2-G also in living cells. The ability of 15d-PGJ2-G to activate the
canonical nuclear factor erythroid 2-related factor (Nrf2) signaling pathway used
by 15d-PGJ2 was assessed, and these studies revealed for the first time that 15d
PGJ2 and 15d-PGJ2-G similarly activated Nrf2 signaling as well as transcription
of target genes of this pathway. Our study challenges previous claims regarding
the ability of MAGL to catalyze PG-G hydrolysis and extend the MAGL substrate
profile beyond the classic monoacylglycerols.
PMID- 25140005
TI - Patient-centered medical home: the future of healthcare delivery?
PMID- 25140006
TI - Republished: creating a safe, reliable hospital at night handover: a case study
in implementation science.
AB - BACKGROUND: We developed protocols to handover patients from day to hospital at
night (H@N) teams. SETTING: NHS paediatric specialist hospital. METHOD: We
observed four handover protocols (baseline, Phases 1, 2 and 3) over 2 years. A
mixed-method study (observation, interviews, task analysis, prospective risk
assessment, document and case note review) explored the impact of different
protocols on performance. INTERVENTION: In Phase 1, a handover protocol was
introduced to resolve problems with the baseline H@N handover. Following this
intervention, two further revisions to the handover occurred, driven by staff
feedback (Phases 2 and 3). RESULTS: Variations in performance between handover
protocols on three process measures, start time efficiency, total length of
handover, and number of distractions and interruptions, were identified.
Univariate regression analysis showed statistically significant differences
between handover protocols on two surrogate outcome measures: number of flagging
omissions and the number of out of hours deteriorations (p=0.04 for Phase 3 vs
Phase 1 for both measures (CI 1.04 to 4.08; CI 1.03 to 4.33), and for Phase 3 vs
Phase 2 (p=0.006 and p=0.001 (CI 1.22 to 5.15; CI 1.62 to 9.0)), respectively).
The Phase 1 and 2 handover protocols were effective at identifying patients whose
clinical condition warranted review overnight. Performance on both surrogate
outcome measures, length of handover and distractions, deteriorated in Phase 3.
CONCLUSIONS: A carefully designed prioritisation process within the H@N handover
can be effective at flagging acutely unwell patients. However, the protocol we
introduced was unsustainable. In a complex healthcare system, sustainable
implementation of new processes may be threatened by conflicting goals.
PMID- 25140007
TI - Republished: clinical implications of the third universal definition of
myocardial infarction.
PMID- 25140008
TI - Of human bondage.
PMID- 25140009
TI - A competitive formation of DNA:RNA hybrid G-quadruplex is responsible to the
mitochondrial transcription termination at the DNA replication priming site.
AB - Human mitochondrial DNA contains a distinctive guanine-rich motif denoted
conserved sequence block II (CSB II) that stops RNA transcription, producing
prematurely terminated transcripts to prime mitochondrial DNA replication.
Recently, we reported a general phenomenon that DNA:RNA hybrid G-quadruplexes
(HQs) readily form during transcription when the non-template DNA strand is
guanine-rich and such HQs in turn regulate transcription. In this work, we show
that transcription of mitochondrial DNA leads to the formation of a stable HQ or
alternatively an unstable intramolecular DNA G-quadruplex (DQ) at the CSB II. The
HQ is the dominant species and contributes to the majority of the premature
transcription termination. Manipulating the stability of the DQ has little effect
on the termination even in the absence of HQ; however, abolishing the formation
of HQs by preventing the participation of either DNA or RNA abolishes the vast
majority of the termination. These results demonstrate that the type of G
quadruplexes (HQ or DQ) is a crucial determinant in directing the transcription
termination at the CSB II and suggest a potential functionality of the co
transcriptionally formed HQ in DNA replication initiation. They also suggest that
the competition/conversion between an HQ and a DQ may regulate the function of a
G-quadruplex-forming sequence.
PMID- 25140010
TI - Invincible DNA tethers: covalent DNA anchoring for enhanced temporal and force
stability in magnetic tweezers experiments.
AB - Magnetic tweezers are a powerful single-molecule technique that allows real-time
quantitative investigation of biomolecular processes under applied force. High
pulling forces exceeding tens of picoNewtons may be required, e.g. to probe the
force range of proteins that actively transcribe or package the genome.
Frequently, however, the application of such forces decreases the sample
lifetime, hindering data acquisition. To provide experimentally viable sample
lifetimes in the face of high pulling forces, we have designed a novel anchoring
strategy for DNA in magnetic tweezers. Our approach, which exploits covalent
functionalization based on heterobifunctional poly(ethylene glycol) crosslinkers,
allows us to strongly tether DNA while simultaneously suppressing undesirable non
specific adhesion. A complete force and lifetime characterization of these
covalently anchored DNA-tethers demonstrates that, compared to more commonly
employed anchoring strategies, they withstand 3-fold higher pulling forces (up to
150 pN) and exhibit up to 200-fold higher lifetimes (exceeding 24 h at a constant
force of 150 pN). This advance makes it possible to apply the full range of
biologically relevant force scales to biomolecular processes, and its
straightforward implementation should extend its reach to a multitude of
applications in the field of single-molecule force spectroscopy.
PMID- 25140011
TI - Structure analysis of free and bound states of an RNA aptamer against ribosomal
protein S8 from Bacillus anthracis.
AB - Several protein-targeted RNA aptamers have been identified for a variety of
applications and although the affinities of numerous protein-aptamer complexes
have been determined, the structural details of these complexes have not been
widely explored. We examined the structural accommodation of an RNA aptamer that
binds bacterial r-protein S8. The core of the primary binding site for S8 on
helix 21 of 16S rRNA contains a pair of conserved base triples that mold the
sugar-phosphate backbone to S8. The aptamer, which does not contain the conserved
sequence motif, is specific for the rRNA binding site of S8. The protein-free RNA
aptamer adopts a helical structure with multiple non-canonical base pairs.
Surprisingly, binding of S8 leads to a dramatic change in the RNA conformation
that restores the signature S8 recognition fold through a novel combination of
nucleobase interactions. Nucleotides within the non-canonical core rearrange to
create a G-(G-C) triple and a U-(A-U)-U quartet. Although native-like S8-RNA
interactions are present in the aptamer-S8 complex, the topology of the aptamer
RNA differs from that of the helix 21-S8 complex. This is the first example of an
RNA aptamer that adopts substantially different secondary structures in the free
and protein-bound states and highlights the remarkable plasticity of RNA
secondary structure.
PMID- 25140012
TI - The evolution of blood pressure and the rise of mankind.
AB - Why is it that only human beings continuously perform acts of heroism? Looking
back at our evolutionary history can offer us some potentially useful insight.
This review highlights some of the major steps in our evolution-more
specifically, the evolution of high blood pressure. When we were fish, the first
kidney was developed to create a standardized internal 'milieu' preserving the
primordial sea within us. When we conquered land as amphibians, the evolution of
the lung required a low systemic blood pressure, which explains why early land
vertebrates (amphibians, reptiles) are such low performers. Gaining independence
from water required the evolution of an impermeable skin and a water-retaining
kidney. The latter was accomplished twice with two different solutions in the two
major branches of vertebrate evolution: mammals excrete nitrogenous waste
products as urea, which can be utilized by the kidney as an osmotic agent to
produce more concentrated urine. Dinosaurs and birds have a distinct nitrogen
metabolism and excrete nitrogen as water-insoluble uric acid-therefore, their
kidneys cannot use urea to concentrate as well. Instead, some birds have
developed the capability to reabsorb water from their cloacae. The convergent
development of a separate small circulation of the lung in mammals and birds
allowed for the evolution of 'high blood-pressure animals' with better
capillarization of the peripheral tissues allowing high endurance performance.
Finally, we investigate why mankind outperforms any other mammal on earth and
why, to this day, we continue to perform acts of heroism on our eternal quest for
personal bliss.
PMID- 25140013
TI - Phosphate, urea and creatinine clearances: haemodialysis adequacy assessed by
weekly monitoring.
AB - BACKGROUND: The specific distribution of phosphate and the control mechanisms for
its plasma level makes phosphate kinetics during haemodialysis (HD) considerably
different from those of urea and creatinine and makes the quantitative evaluation
of adequacy of phosphate removal difficult. We propose the application of
equivalent continuous clearance (ECC) as a phosphate adequacy parameter and
compare it with ECC for creatinine and urea. METHODS: Three consecutive dialysis
sessions were evaluated for 25 patients on maintenance HD. Concentrations of
phosphate, urea and creatinine in plasma were measured every 1h during the
treatment and 45 min after, and every 30 min in dialysate. ECC was calculated
using the removed solute mass assessed in dialysate and weekly solute profile in
plasma. Similar calculations were performed also for the midweek dialysis session
only. Different versions of the reference concentration for ECC were applied.
RESULTS: ECC with peak average reference concentration was 5.4 +/- 1.0 for
phosphate, 7.0 +/- 1.0 for urea and 4.7 +/- 1.0 mL/min for creatinine. ECC for
urea and creatinine were well correlated in contrast to the correlations of ECC
for phosphate versus urea and creatinine. Midweek ECC were higher than weekly
ECC, but they were well correlated for urea and creatinine, but only weakly for
phosphate. CONCLUSIONS: HD adequacy monitoring for phosphate may be performed
using ECC, but it is less predictable than similar indices for urea and
creatinine. The values of ECC for phosphate are within the range expected for its
molecular size compared with those for urea and creatinine.
PMID- 25140015
TI - High-dose isoproterenol testing for diagnosis of arrhythmogenic right ventricular
dysplasia/cardiomyopathy: is there a role?
PMID- 25140014
TI - Neprilysin inhibition in chronic kidney disease.
AB - Despite current practice, patients with chronic kidney disease (CKD) are at
increased risk of progression to end-stage renal disease and cardiovascular
events. Neprilysin inhibition (NEPi) is a new therapeutic strategy with potential
to improve outcomes for patients with CKD. NEPi enhances the activity of
natriuretic peptide systems leading to natriuresis, diuresis and inhibition of
the renin-angiotensin system (RAS), which could act as a potentially beneficial
counter-regulatory system in states of RAS activation such as chronic heart
failure (HF) and CKD. Early NEPi drugs were combined with angiotensin-converting
enzyme inhibitors but were associated with unacceptable rates of angioedema and,
therefore, withdrawn. However, one such agent (omapatrilat) showed promise of
NEP/RAS inhibition in treating CKD in animal models, producing greater reductions
in proteinuria, glomerulosclerosis and tubulointerstitial fibrosis compared with
isolated RAS inhibition. A new class of drug called angiotensin receptor
neprilysin inhibitor (ARNi) has been developed. One such drug, LCZ696, has shown
substantial benefits in trials in hypertension and HF. In CKD, HF is common due
to a range of mechanisms including hypertension and structural heart disease
(including left ventricular hypertrophy), suggesting that ARNi could benefit
patients with CKD by both retarding the progression of CKD (hence delaying the
need for renal replacement therapy) and reducing the risk of cardiovascular
disease. LCZ696 is now being studied in a CKD population.
PMID- 25140016
TI - The ideal end point for ablation in postinfarction ventricular tachycardia: one
may not fit all.
PMID- 25140017
TI - Unravelling the paradoxical effects of ganglia ablation.
PMID- 25140019
TI - Ablation versus drugs: what is the best first-line therapy for paroxysmal atrial
fibrillation? Antiarrhythmic drugs are outmoded and catheter ablation should be
the first-line option for all patients with paroxysmal atrial fibrillation: pro.
PMID- 25140018
TI - Electroporation: past and future of catheter ablation.
PMID- 25140020
TI - Ablation versus drugs: what is the best first-line therapy for paroxysmal atrial
fibrillation? Antiarrhythmic drugs are outmoded and catheter ablation should be
the first-line option for all patients with paroxysmal atrial fibrillation: con.
PMID- 25140021
TI - Postablation scar-related atrial tachycardia: turning the spotlight on P-wave
analysis and window settings.
PMID- 25140022
TI - Electrocardiogram mapping-reentry: final frontier?
PMID- 25140023
TI - Bradycardia-dependent conduction block into pulmonary vein after isolation.
PMID- 25140024
TI - Anatomic analysis of the left atrial appendage after closure with the LARIAT
device.
PMID- 25140025
TI - Inappropriate shocks due to subcutaneous air in a patient with a subcutaneous
cardiac defibrillator.
PMID- 25140026
TI - Is medical research in danger of suffering the same fate as the NHS?
PMID- 25140027
TI - Scleral granuloma revealing intraocular foreign body.
PMID- 25140028
TI - An unusual cause of gastrointestinal bleeding-migration of a hip prosthesis.
PMID- 25140029
TI - Bodybuilding, exogenous testosterone use and myocardial infarction.
PMID- 25140030
TI - End-stage renal disease and survival in people with diabetes: a national database
linkage study.
AB - BACKGROUND: Increasing prevalence of diabetes worldwide is projected to lead to
an increase in patients with end-stage renal disease (ESRD) requiring renal
replacement therapy (RRT). AIM: To provide contemporary estimates of the
prevalence of ESRD and requirement for RRT among people with diabetes in a
nationwide study and to report associated survival. METHODS: Data were extracted
and linked from three national databases: Scottish Renal Registry, Scottish Care
Initiative-Diabetes Collaboration and National Records of Scotland death data.
Survival analyses were modelled with Cox regression. RESULTS: Point prevalence of
chronic kidney disease (CKD)5 in 2008 was 1.63% of 19 414 people with type 1
diabetes (T1DM) compared with 0.58% of 167 871 people with type 2 diabetes (T2DM)
(odds ratio for DM type 0.97, P = 0.77, on adjustment for duration. Although 83%
of those with T1DM and CKD5 and 61% of those with T2DM and CKD5 were receiving
RRT, there was no difference when adjusted for age, sex and DM duration (odds
ratio for DM type 0.83, P = 0.432). Diabetic nephropathy was the primary renal
diagnosis in 91% of people with T1DM and 58% of people with T2DM on RRT. Median
survival time from initiation of RRT was 3.84 years (95% CI 2.77, 4.62) in T1DM
and 2.16 years (95% CI: 1.92, 2.38) in T2DM. CONCLUSION: Considerable numbers of
patients with diabetes continue to progress to CKD5 and RRT. Almost half of all
RRT cases in T2DM are considered to be due to conditions other than diabetic
nephropathy. Median survival time for people with diabetes from initiation of RRT
remains poor. These prevalence data are important for future resource planning.
PMID- 25140031
TI - Improved outcomes of high-risk emergency medical admissions cared for by
experienced physicians.
AB - BACKGROUND: Physician experience has been shown to improve clinical outcomes.
Limited numbers of experienced clinicians make it unfeasible that they would care
for all patients. We hypothesized that physician experience would impact outcomes
for patients with high, but not low, risk of mortality. METHODS: All emergency
admissions from 2002 to 2013 were studied. Two groups at low and high risk for
mortality (1.3% (95% CI: 1.13, 1.62) vs. 19.4% (95% CI: 18.5, 20.3)) were defined
by a risk prediction method comprising acute Illness Severity Score, Charlson
Comorbidity Index and sepsis status. Length of stay (LOS) and 30-day in-hospital
mortality were the primary end points. Consultant experience was studied
univariately and also entered into a multiple logistic regression model to
predict 30-day in-hospital survival. A zero-truncated Poisson regression model
assessed LOS and incidence rate ratios (IRR) were calculated. RESULTS: Over the
12-year study period 66 933 admissions were recorded in 36 271 patients. High
risk patients cared for by more experienced (>=20 years qualified) physicians had
a lower 30-day in-hospital mortality (19.4 vs. 17.1% P < 0.001), relative risk
reduction 11.9%. The multivariable odds ratio of a 30-day in-hospital death for
an experienced physician was 0.89 (95% CI: 0.82, 0.97; P = 0.009). LOS was
shorter for high-risk patients allocated to experienced physicians with a
multivariable IRR of 0.77 (95% CI: 0.94, 0.99; P = 0.02). No difference in
outcomes was found for low-risk patients. CONCLUSION: High-risk but not low-risk
patients have improved outcomes when cared for by physicians with greater
experience.
PMID- 25140032
TI - Effects of an educational intervention of physical activity for children and
adolescents with cystic fibrosis: a randomized controlled trial.
AB - BACKGROUND: Regular aerobic exercise in patients with cystic fibrosis (CF)
improves aerobic conditioning and delays disease progression, resulting in better
quality of life. The purpose of this study was to evaluate the effect of an
aerobic exercise program based on verbal and written guidelines on maximum
exercise capacity using a cardiopulmonary exercise test, quality of life, and the
self-reported aerobic exercise practice of children and adolescents with CF.
METHODS: This randomized controlled trial followed guidelines for physical
exercise in a CF center. Subjects were assigned to 2 groups: intervention (group
1), with 17 subjects; and control (group 2), also with 17 subjects. Data were
collected from October 2010 to October 2011, and the study population comprised 7
20-y-old children and adolescents with CF. The intervention consisted of handing
out a manual with guidelines for aerobic physical exercises and reinforcing
recommendations in telephone calls every 2 weeks. RESULTS: Thirty-four subjects
were included in the study, 20 of whom were boys (58.5%). The groups were similar
at baseline. In group 1, 6 subjects (35.2%) reported practicing physical
exercises regularly. The mean age was 13.4 +/- 2.8 y, the mean percent-of
predicted FEV1 was 95.5 +/- 17.9%, and the mean peak oxygen uptake (VO2 )
relative to body mass was 34.9 +/- 9.0 mL/kg/min. In group 2, 4 subjects (23.5%)
reported practicing physical exercises regularly. The mean age was 12.7 +/- 3.3
y, the mean percent-of-predicted FEV1 was 100.1 +/- 21.2%, and the mean peak VO2
was 33.2 +/- 8.2 mL/kg/min. In group 1, there was a significant increase in
physical exercise practice as reported by subjects after 3 months of intervention
compared with group 2 (P = .01). No statistically significant differences were
found for the other variables. CONCLUSIONS: Verbal and written guidelines for
aerobic exercise, together with supervision over the telephone, had a positive
impact on the self-reported regular physical exercise practice of children and
adolescents. However, no improvement was found in lung function and maximum
exercise capacity or domains of the quality of life questionnaire.
PMID- 25140033
TI - Open-mouthpiece ventilation versus nasal mask ventilation in subjects with COPD
exacerbation and mild to moderate acidosis: a randomized trial.
AB - BACKGROUND: Open mouthpiece ventilation is efficacious in patients with
neuromuscular disease. We used this ventilation technique in patients with
exacerbations of COPD with mild to moderate acidosis. METHODS: The study was
performed in 2 respiratory monitoring care units. Fifty subjects with
exacerbations of COPD, breathing frequency > 25, PaCO2 > 45, and pH between 7.25
and 7.30, as well as Kelly scale <= 2 were enrolled. Subjects were randomly
assigned to receive noninvasive ventilation (NIV) via nasal mask or mouthpiece
ventilation. The primary outcome was improvement in arterial blood gases.
Arterial blood gases and breathing frequency were recorded 2 h after the start of
the enrollment and then after 12, 24, and 48 h. The duration of NIV, hospital
stay, and acceptability of the interface (mouthpiece or nasal mask) using a
Likert scale were assessed. RESULTS: No subjects had deterioration of gas
exchange. The 2 groups had similar trends in arterial blood gases and breathing
frequency. No differences in duration of NIV or hospital stay were noted.
However, a significant difference in acceptability was found: subjects preferred
mouthpiece ventilation (P < .01). CONCLUSIONS: Open mouthpiece ventilation is a
useful technique and may prevent further deterioration of gas exchange in COPD
patients with mild to moderate acidosis (similar to traditional NIV delivered by
a nasal mask). www.chictr.org registration ChiCTR-TRC-12002672.
PMID- 25140034
TI - Voluntary is better than involuntary cough peak flow for predicting re-intubation
after scheduled extubation in cooperative subjects.
AB - BACKGROUND: In this study, we compared the predictive accuracy of voluntary cough
peak flow (V-CPF) and involuntary cough peak flow (IV-CPF) for re-intubation in
mechanically ventilated subjects. METHODS: Endotracheally intubated patients who
passed a spontaneous breathing trial and assessment of readiness for extubation
were enrolled. Before extubation, V-CPF and IV-CPF were measured. Re-intubation
was recorded at 72 h after extubation. RESULTS: A total of 115 extubations in 106
cooperative subjects (including 9 subjects with second extubation) and 5
extubations in 5 uncooperative subjects were recorded. At 72 h, 20 (17.4%) and 1
(25%) instances of re-intubation occurred in cooperative and uncooperative
subjects, respectively. In cooperative subjects, those who had been successfully
extubated had higher V-CPF than re-intubated subjects (81.3 +/- 41.4 vs 51.3 +/-
31.7, P = .003). However, rates were not significantly different with IV-CPF
(70.9 +/- 39.8 vs 55.7 +/- 37.9, P = .121). Areas under the curve of the receiver
operating characteristic in V-CPF and IV-CPF were 0.743 +/- 0.057 and 0.632 +/-
0.069 (P < .001 and P = .058, respectively, compared with area under the curve =
0.5). V-CPF had higher predictive accuracy for re-intubation than IV-CPF (P =
.034). In subjects with a lower quartile and third quartile V-CPF (<= 43.2 L/min
and 43.2-68.4 L/min, respectively), V-CPF was similar to IV-CPF. However, in
second quartile and upper quartile V-CPF (68.4-99.0 L/min and > 99.0 L/min,
respectively), V-CPF was higher than IV-CPF (82.1 +/- 9.6 vs 66.6 +/- 19.5 L/min,
P < .001; 135.5 +/- 29.8 vs 116.2 +/- 38.2 L/min, P = .006, respectively).
Overall, V-CPF was higher than IV-CPF (76.0 +/- 41.4 vs 68.2 +/- 39.7, P = .003).
In uncooperative subjects, the IV-CPF was higher than V-CPF (40.2 +/- 10.2 vs
79.2 +/- 29.0, P = .042). CONCLUSIONS: V-CPF is noninvasive. It is much more
accurate than IV-CPF as a predictor of re-intubation in cooperative patients
because the IV-CPF may underestimate cough strength in patients with high V-CPF.
However, it is unclear which is optimal for use in uncooperative patients.
PMID- 25140035
TI - Identification of 9 serum microRNAs as potential noninvasive biomarkers of human
astrocytoma.
AB - BACKGROUND: Circulating microRNAs (miRNAs) are emerging as promising biomarkers
for human cancer. In the current study, we investigated the potential use of
serum miRNAs as biomarkers for diagnosis and prognosis in a cohort of Chinese
astrocytoma patients. METHODS: An initial screening of the circulating miRNA
expression profile was performed on pooled serum samples from 10 preoperative
patients and 10 healthy controls using a TaqMan low-density array. The selected
serum miRNAs were then validated in 90 preoperative patients and 110 healthy
controls who were randomly divided into a training set and a validation set. An
additional double-blind test was performed in 50 astrocytomas and 50 controls to
assess the serum miRNA-based biomarker accuracy in predicting astrocytoma. The
differentially expressed miRNAs were evaluated in paired preoperative and
postoperative serum samples from 73 astrocytoma patients. The correlation of the
miRNA levels with survival in astrocytoma samples was estimated. RESULTS: Nine
serum miRNAs were significantly increased in the astrocytoma patients. The
biomarker composed of these 9 miRNAs had high sensitivity, specificity, and
accuracy. These 9 miRNAs were markedly decreased in the serum after operation.
The upregulation of miR-20a-5p, miR-106a-5p, and miR-181b-5p was associated with
advanced clinical stages of astrocytoma. Kaplan-Meier survival analysis showed
that the high expression of miR-19a-3p, miR-106a-5p, and miR-181b-5p was
significantly associated with poor patient survival. Finally, the combined 3
miRNAs panel was an important prognostic predictor, independent of other
clinicopathological factors. CONCLUSIONS: The results indicated the potential of
serum miRNAs as novel diagnostic and prognostic biomarkers for human astrocytoma.
PMID- 25140036
TI - TERT promoter mutations: a novel independent prognostic factor in primary
glioblastomas.
AB - BACKGROUND: Activating somatic mutations in the promoter region of the telomerase
reverse transcriptase gene (TERT) have been detected in several cancers. In this
study we investigated the TERT promoter mutations and their impact on patient
survival in World Health Organization grade IV glioblastoma multiforme (GBM).
METHODS: The TERT core promoter region containing the previously described
mutations and a common functional polymorphism (rs2853669) was sequenced in
tumors and blood samples from 192 GBM patients. O(6)-methylguanine-DNA
methyltransferase (MGMT) promoter methylation status was assessed by
pyrosequencing in 177 (92.2%) cases. Relevant clinical data were obtained from a
prospectively maintained electronic database. RESULTS: We detected specific (-124
C>T and -146 C>T) TERT promoter mutations in 143/178 (80.3%) primary GBM and 4/14
(28.6%) secondary GBM (P < .001). The presence of TERT mutations was associated
with poor overall survival, and the effect was confined to the patients who did
not carry the variant G-allele for the rs2853669 polymorphism. An exploratory
analysis suggested that TERT mutations might be prognostic only in patients who
had incomplete resections and no temozolomide chemotherapy. CONCLUSIONS: In this
study, specific TERT promoter mutations were markers of primary GBM and predicted
patient survival in conjunction with a common functional polymorphism. The
prognostic impact of TERT mutations was absent in patients with complete
resections and temozolomide chemotherapy. If confirmed in additional studies,
these findings may have clinical implications, that is, TERT mutations appear to
characterize tumors that require aggressive treatment.
PMID- 25140037
TI - Efficacy of cabazitaxel in mouse models of pediatric brain tumors.
AB - BACKGROUND: There is an unmet need in the treatment of pediatric brain tumors for
chemotherapy that is efficacious, avoids damage to the developing brain, and
crosses the blood-brain barrier. These experiments evaluated the efficacy of
cabazitaxel in mouse models of pediatric brain tumors. METHODS: The antitumor
activity of cabazitaxel and docetaxel were compared in flank and orthotopic
xenograft models of patient-derived atypical teratoid rhabdoid tumor (ATRT),
medulloblastoma, and central nervous system primitive neuroectodermal tumor (CNS
PNET). Efficacy of cabazitaxel and docetaxel were also assessed in the Smo/Smo
spontaneous mouse medulloblastoma tumor model. RESULTS: This study observed
significant tumor growth inhibition in pediatric patient-derived flank xenograft
tumor models of ATRT, medulloblastoma, and CNS-PNET after treatment with either
cabazitaxel or docetaxel. Cabazitaxel, but not docetaxel, treatment resulted in
sustained tumor growth inhibition in the ATRT and medulloblastoma flank xenograft
models. Patient-derived orthotopic xenograft models of ATRT, medulloblastoma, and
CNS-PNET showed significantly improved survival with treatment of cabazitaxel.
CONCLUSION: These data support further testing of cabazitaxel as a therapy for
treating human pediatric brain tumors.
PMID- 25140040
TI - Time to diagnosis of axial spondylarthritis in clinical practice: signs of
improving awareness?
PMID- 25140038
TI - Periostin is a novel therapeutic target that predicts and regulates glioma
malignancy.
AB - BACKGROUND: Periostin is a secreted matricellular protein critical for epithelial
mesenchymal transition and carcinoma metastasis. In glioblastoma, it is highly
upregulated compared with normal brain, and existing reports indicate potential
prognostic and functional importance in glioma. However, the clinical
implications of periostin expression and function related to its therapeutic
potential have not been fully explored. METHODS: Periostin expression levels and
patterns were examined in human glioma cells and tissues by quantitative real
time PCR and immunohistochemistry and correlated with glioma grade, type,
recurrence, and survival. Functional assays determined the impact of altering
periostin expression and function on cell invasion, migration, adhesion, and
glioma stem cell activity and tumorigenicity. The prognostic and functional
relevance of periostin and its associated genes were analyzed using the TCGA and
REMBRANDT databases and paired recurrent glioma samples. RESULTS: Periostin
expression levels correlated directly with tumor grade and recurrence, and
inversely with survival, in all grades of adult human glioma. Stromal deposition
of periostin was detected only in grade IV gliomas. Secreted periostin promoted
glioma cell invasion and adhesion, and periostin knockdown markedly impaired
survival of xenografted glioma stem cells. Interactions with alphavbeta3 and
alphavbeta5 integrins promoted adhesion and migration, and periostin abrogated
cytotoxicity of the alphavbeta3/beta5 specific inhibitor cilengitide. Periostin
associated gene signatures, predominated by matrix and secreted proteins,
corresponded to patient prognosis and functional motifs related to increased
malignancy. CONCLUSION: Periostin is a robust marker of glioma malignancy and
potential tumor recurrence. Abrogation of glioma stem cell tumorigenicity after
periostin inhibition provides support for exploring the therapeutic impact of
targeting periostin.
PMID- 25140041
TI - Prevention of new osteitis on magnetic resonance imaging in patients with early
axial spondyloarthritis during 3 years of continuous treatment with etanercept:
data of the ESTHER trial.
AB - OBJECTIVE: The aim of this study was to assess the degree of fluctuation of
osteitis on MRI during long-term treatment with etanercept (ETN) in patients with
early axial SpA (axSpA) with active inflammation (osteitis) on whole-body MRI in
the spine and/or the SI joints at baseline. METHODS: We analysed MRI data from
328 SI joint quadrants and 943 spine vertebral units (VUs) in terms of osteitis
in the pooled data set of 41 patients who were treated with ETN for 3 consecutive
years. Scoring was performed by two blinded radiologists at baseline, year 2 and
year 3. RESULTS: Through years 2 and 3, osteitis on MRI resolved completely in 56
of 144 (38.9%) SI joint quadrants and in 20 of 40 (50%) VUs affected at baseline,
while persistent osteitis was found in 24 of 144 (16.7%) SI joint quadrants and
in 8 of 40 (20.0%) spine VUs. The development of new osteitis in sites that were
free of osteitis at baseline only occurred in 2 of 131 (1.5%) SI joint quadrants
and in 3 of 862 (0.4%) spine VUs in both year 2 and year 3. CONCLUSION: There was
a consistently small amount of osteitis on MRI in patients with early axSpA
compared with baseline values, and only a very low rate of new-onset osteitis was
found during 3 years of continuous treatment with ETN. TRIAL REGISTRATION:
www.clinicaltrials.gov, NCT00844142.
PMID- 25140039
TI - Phase I/randomized phase II study of afatinib, an irreversible ErbB family
blocker, with or without protracted temozolomide in adults with recurrent
glioblastoma.
AB - BACKGROUND: This phase I/II trial evaluated the maximum tolerated dose (MTD) and
pharmacokinetics of afatinib plus temozolomide as well as the efficacy and safety
of afatinib as monotherapy (A) or with temozolomide (AT) vs temozolomide
monotherapy (T) in patients with recurrent glioblastoma (GBM). METHODS: Phase I
followed a traditional 3 + 3 dose-escalation design to determine MTD. Treatment
cohorts were: afatinib 20, 40, and 50 mg/day (plus temozolomide 75 mg/m(2)/day
for 21 days per 28-day cycle). In phase II, participants were randomized
(stratified by age and KPS) to receive A, T or AT; A was dosed at 40 mg/day and T
at 75 mg/m(2) for 21 of 28 days. Primary endpoint was progression-free survival
rate at 6 months (PFS-6). Participants were treated until intolerable adverse
events (AEs) or disease progression. RESULTS: Recommended phase II dose was 40
mg/day (A) + T based on safety data from phase I (n = 32). Most frequent AEs in
phase II (n = 119) were diarrhea (71% [A], 82% [AT]) and rash (71% [A] and 69%
[AT]). Afatinib and temozolomide pharmacokinetics were unaffected by
coadministration. Independently assessed PFS-6 rate was 3% (A), 10% (AT), and 23%
(T). Median PFS was longer in afatinib-treated participants with epidermal growth
factor receptor (EFGR) vIII-positive tumors versus EGFRvIII-negative tumors. Best
overall response included partial response in 1 (A), 2 (AT), and 4 (T)
participants and stable disease in 14 (A), 14 (AT), and 21 (T) participants.
CONCLUSIONS: Afatinib has a manageable safety profile but limited single-agent
activity in unselected recurrent GBM patients.
PMID- 25140043
TI - Use of a water pipe is not an alternative to other tobacco or substance use among
adolescents: results from a national survey in Sweden.
AB - INTRODUCTION: Studies of social characteristics and substance use patterns among
young users of water pipe are rare in Western countries, and no such study has
been conducted in Sweden. METHODS: Cross-sectional study based on a national
survey conducted in 2011, including 4,710 primary school students (15 years of
age) and 3,624 high school students (17 years of age). Prevalence of lifetime and
current water pipe use was compared among subgroups defined by other substance
use, that is, cigarettes, snus, alcohol, and illicit drugs. Logistic regression
was employed to calculate odds ratios (OR) of water pipe use and corresponding
95% confidence intervals (CI), conditionally on sociodemographic characteristics.
RESULTS: Use of water pipe was associated with the use of other substances in
both age groups. In particular, current use of water pipe at the age of 15 years
was strongly associated with current cigarette smoking (OR = 6.46; CI = 5.13
8.14); use of snus (OR = 5.62; CI = 3.94-7.96); binge drinking (OR = 7.39; CI =
5.88-9.31); drunkenness (OR = 7.05; CI = 5.60-8.88); and recent use of illicit
drugs (OR = 14.20; CI = 9.18-22.19). Annual alcohol consumption predicted water
pipe use in a dose-response fashion. Cigarette smokers willing to quit used water
pipe to a lower extent than smokers who did not intend to quit. Being an
exclusive smoker of water pipe was associated with substance use when compared
with a nonsmoker of tobacco, but not when compared with an exclusive smoker of
cigarettes. CONCLUSIONS: Water pipe use among adolescents in Sweden is not a
recreational tobacco use alternative to cigarettes and should be regarded as a
marker of multiple substance use.
PMID- 25140042
TI - Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated
splicing events.
AB - Imbalanced splicing of premessenger RNA is typical of tumorous malignancies, and
the regulatory mechanisms involved in several tumorigenesis-associated splicing
events are identified. Elevated expression of serine-arginine protein kinase 1
(SRPK1) may participate in the pathway responsible for the dysregulation of
splicing events in malignant tumor cells. In this study, we observed a
correlation between the cytoplasmic accumulation of RNA-binding motif protein 4
(RBM4) and up-regulated SRPK1 in breast cancer cells. The production of the IR-B
and MCL-1S transcripts was induced separately by the overexpression of RBM4 and
SRPK1 gene silencing. Overexpressed RBM4 simultaneously bound to the CU-rich
elements within the MCL-1 exon2 and the downstream intron, which subsequently
facilitated the exclusion of the regulated exon. Breast cancer cells are deprived
of apoptotic resistance through the RBM4-mediated up-regulation of the IR-B and
MCL-1S transcripts. These findings suggest that the splicing events regulated by
the SRPK1-RMB4 network may contribute to tumorigenesis through altered
sensitivity to apoptotic signals in breast cancer cells.
PMID- 25140044
TI - Assessing the performance of two lung age equations on the Australian population:
using data from the cross-sectional BOLD-Australia study.
AB - INTRODUCTION: Lung age, a simple concept for patients to grasp, is frequently
used as an aid in smoking cessation programs. Lung age equations should be
continuously updated and should be made relevant for target populations. We
observed how new lung age equations developed for Australian populations
performed when utilizing the Burden of Obstructive Lung Disease (BOLD)-Australia
dataset compared to more commonly used equations. METHODS: Data from a cross
sectional population study of noninstitutionalized Australians aged >=40 years
with analysis restricted to Caucasians <75 years. Lung age calculated using
equations developed by Newbury et al. and Morris and Temple was compared with
chronological age by smoking status and within smoking status. RESULTS: There
were 2,793 participants with a mean age of 57 (+/-10 SD) years. More than half
(52%) ever smoked, and 10.4% were current smokers. Prevalence of chronic
obstructive pulmonary disease stage I or higher was 13.4% (95% confidence
interval = 12.2, 14.7). For both genders, newer Newbury equations estimated lung
ages significantly higher than actual age across all smoking groups (p < .05).
Morris and Temple equations resulted in lung age estimates significantly lower
than chronological age for nonsmokers (p < .05) but no difference among current
smokers. Both equations showed exposure to smoking had lung ages higher than
never-smokers (p < .001). Lung age also increased with increased pack-years.
CONCLUSIONS: This supports the use of updated equations suited to the population
of interest. The Australian Newbury equations performed well in the BOLD
Australia dataset, providing more meaningful lung age profile compared to
chronological age among smokers. Using equations not developed or ideally suited
for our population is likely to produce misleading results.
PMID- 25140045
TI - Smoking restrictions in homes after implementation of a smoking ban in public
places.
AB - INTRODUCTION: This Canadian study examines the prevalence of smoking restrictions
in homes before and after the implementation of a public smoking ban, and their
relation to tobacco use and cessation among a cohort of smokers. METHODS: Data
were from a longitudinal cohort study of 1,058 smokers in the province of Quebec,
Canada. Baseline data were collected through a population-based survey conducted
1 month before the implementation of the smoking ban with a representative sample
of smokers. Follow-up data were collected 18 months after the ban with a response
rate of 68%. Logistic regressions, paired t tests and chi-square statistics were
used to examine the factors associated with smoking restrictions in homes,
cigarette consumption, and quit attempts. RESULTS: Many smokers imposed partial
or full smoking restrictions in their homes but proportions of smoke-free homes
did not change significantly between baseline and follow-up. The presence of
young children and nonsmokers significantly predicted full smoking restriction in
the home. Knowledge about risks associated with exposure to secondhand smoke
(SHS) and skepticism about the efficacy of methods to reduce exposure in the home
also predicted maintenance of voluntary smoking restrictions in homes. The uptake
of smoke-free homes was not associated with the quantity of cigarettes smoked or
quit attempts. CONCLUSIONS: No significant change in home smoking bans was found
18 months after implementation of a public smoking ban. There remains a need for
efforts to better inform smokers about health risks from exposure to SHS in homes
and the reality that strategies other than a total smoking ban inside the home
are ineffective.
PMID- 25140046
TI - Neural coding of assessing another person's knowledge based on nonverbal cues.
AB - For successful communication, conversational partners need to estimate each
other's current knowledge state. Nonverbal facial and bodily cues can reveal
relevant information about how confident a speaker is about what they are saying.
Using functional magnetic resonance imaging, we aimed to identify brain regions
that encode how confident a speaker is perceived to be. Participants viewed
videos of people answering general knowledge questions and judged each
respondent's confidence in their answer. Our results suggest a distinct role of
two neural networks known to support social inferences, the so-called mentalizing
and the mirroring network. While activation in both networks underlies the
processing of nonverbal cues, only activity in the mentalizing network, most
notably the medial prefrontal cortex and the bilateral temporoparietal junction,
is modulated by how confident the respondent is judged to be. Our results support
an integrative account of the mirroring and mentalizing network, in which the two
systems support each other in aiding pragmatic processing.
PMID- 25140047
TI - Oxytocin tempers calculated greed but not impulsive defense in predator-prey
contests.
AB - Human cooperation and competition is modulated by oxytocin, a hypothalamic
neuropeptide that functions as both hormone and neurotransmitter. Oxytocin's
functions can be captured in two explanatory yet largely contradictory
frameworks: the fear-dampening (FD) hypothesis that oxytocin has anxiolytic
effects and reduces fear-motivated action; and the social approach/avoidance
(SAA) hypothesis that oxytocin increases cooperative approach and facilitates
protection against aversive stimuli and threat. We tested derivations from both
frameworks in a novel predator-prey contest game. Healthy males given oxytocin or
placebo invested as predator to win their prey's endowment, or as prey to protect
their endowment against predation. Neural activity was registered using 3T-MRI.
In prey, (fear-motivated) investments were fast and conditioned on the amygdala.
Inconsistent with FD, oxytocin did not modulate neural and behavioral responding
in prey. In predators, (greed-motivated) investments were slower, and conditioned
on the superior frontal gyrus (SFG). Consistent with SAA, oxytocin reduced
predator investment, time to decide and activation in SFG. Thus, whereas oxytocin
does not incapacitate the impulsive ability to protect and defend oneself, it
lowers the greedy and more calculated appetite for coming out ahead.
PMID- 25140048
TI - A meta-analysis of the anterior cingulate contribution to social pain.
AB - Many functional magnetic resonance imaging studies have explored the neural
correlates of social pain that results from social threat, exclusion, rejection,
loss or negative evaluation. Although activations have consistently been reported
within the anterior cingulate cortex (ACC), it remains unclear which ACC
subdivision is particularly involved. To provide a quantitative estimation of the
specific involvement of ACC subdivisions in social pain, we conducted a voxel
based meta-analysis. The literature search identified 46 articles that included
940 subjects, the majority of which used the cyberball task. Significant
likelihoods of activation were found in both the ventral and dorsal ACC for both
social pain elicitation and self-reported distress during social pain. Self
reported distress involved more specifically the subgenual and pregenual ACC than
social pain-related contrasts. The cyberball task involved the anterior
midcingulate cortex to a lesser extent than other experimental tasks. During
social pain, children exhibited subgenual activations to a greater extent than
adults. Finally, the ventro-dorsal gradient of ACC activations in cyberball
studies was related to the length of exclusion phases. The present meta-analysis
contributes to a better understanding of the role of ACC subdivisions in social
pain, and it could be of particular importance for guiding future studies of
social pain and its neural underpinnings.
PMID- 25140049
TI - Social identity modifies face perception: an ERP study of social categorization.
AB - Two studies examined whether social identity processes, i.e. group identification
and social identity threat, amplify the degree to which people attend to social
category information in early perception [assessed with event-related brain
potentials (ERPs)]. Participants were presented with faces of Muslims and non
Muslims in an evaluative priming task while ERPs were measured and implicit
evaluative bias was assessed. Study 1 revealed that non-Muslims showed stronger
differentiation between ingroup and outgroup faces in both early (N200) and later
processing stages (implicit evaluations) when they identified more strongly with
their ethnic group. Moreover, identification effects on implicit bias were
mediated by intergroup differentiation in the N200. In Study 2, social identity
threat (vs control) was manipulated among Muslims. Results revealed that high
social identity threat resulted in stronger differentiation of Muslims from non
Muslims in early (N200) and late (implicit evaluations) processing stages, with
N200 effects again predicting implicit bias. Combined, these studies reveal how
seemingly bottom-up early social categorization processes are affected by
individual and contextual variables that affect the meaning of social identity.
Implications of these results for the social identity perspective as well as
social cognitive theories of person perception are discussed.
PMID- 25140050
TI - The association between the 5-HTTLPR and neural correlates of fear conditioning
and connectivity.
AB - Strong evidence links the 5-HTTLPR genotype to the modulation of amygdala
reactivity during fear conditioning, which is considered to convey the increased
vulnerability for anxiety disorders in s-allele carriers. In addition to amygdala
reactivity, the 5-HTTLPR has been shown to be related to alterations in
structural and effective connectivity. The aim of this study was to investigate
the effects of 5-HTTLPR genotype on amygdala reactivity and effective
connectivity during fear conditioning, as well as structural connectivity [as
measured by diffusion tensor imaging (DTI)]. To integrate different
classification strategies, we used the bi-allelic (s-allele vs l/l-allele group)
as well as the tri-allelic (low-functioning vs high-functioning) classification
approach. S-allele carriers showed exaggerated amygdala reactivity and elevated
amygdala-insula coupling during fear conditioning (CS + > CS-) compared with the
l/l-allele group. In addition, DTI analysis showed increased fractional
anisotropy values in s-allele carriers within the uncinate fasciculus. Using the
tri-allelic classification approach, increased amygdala reactivity and amygdala
insula coupling were observed in the low-functioning compared with the high
functioning group. No significant differences between the two groups were found
in structural connectivity. The present results add to the current debate on the
influence of the 5-HTTLPR on brain functioning. These differences between s
allele and l/l-allele carriers may contribute to altered vulnerability for
psychiatric disorders.
PMID- 25140052
TI - Outflanking RANK with a designer antagonist cytokine.
AB - Members of the tumor necrosis factor (TNF) superfamily of cytokines are
noncovalently linked trimers that play important roles in regulating the immune
system and have emerged as successful therapeutic targets in various rheumatic
and autoimmune conditions. Traditionally, antibodies to cytokines or receptor-Fc
fusion proteins have been used to block signaling by TNF family cytokines. In
this issue of Science Signaling, Warren et al. have taken a new approach to
blocking the action of the TNF superfamily member RANKL [receptor activator of
nuclear factor kappaB (RANK) ligand], which plays an important role in regulating
bone turnover through stimulation of its receptor RANK on osteoclasts. Beginning
with a single-chain fusion protein of three RANKL subunits, the authors used
directed mutagenesis to generate a trimer consisting of a nonreceptor binding
subunit fused to two "super-agonist" subunits that have increased affinity for
RANK. This molecule antagonized the osteoclastogenic activity of wild-type RANKL
in vitro and in vivo, thus providing insights into RANK signaling and a paradigm
for the development of other antagonists of TNF family cytokines.
PMID- 25140051
TI - Automatic emotion processing as a function of trait emotional awareness: an fMRI
study.
AB - It is unclear whether reflective awareness of emotions is related to extent and
intensity of implicit affective reactions. This study is the first to investigate
automatic brain reactivity to emotional stimuli as a function of trait emotional
awareness. To assess emotional awareness the Levels of Emotional Awareness Scale
(LEAS) was administered. During scanning, masked happy, angry, fearful and
neutral facial expressions were presented to 46 healthy subjects, who had to rate
the fit between artificial and emotional words. The rating procedure allowed
assessment of shifts in implicit affectivity due to emotion faces. Trait
emotional awareness was associated with increased activation in the primary
somatosensory cortex, inferior parietal lobule, anterior cingulate gyrus, middle
frontal and cerebellar areas, thalamus, putamen and amygdala in response to
masked happy faces. LEAS correlated positively with shifts in implicit affect
caused by masked happy faces. According to our findings, people with high
emotional awareness show stronger affective reactivity and more activation in
brain areas involved in emotion processing and simulation during the perception
of masked happy facial expression than people with low emotional awareness. High
emotional awareness appears to be characterized by an enhanced positive affective
resonance to others at an automatic processing level.
PMID- 25140053
TI - The ErbB4 CYT2 variant protects EGFR from ligand-induced degradation to enhance
cancer cell motility.
AB - The epidermal growth factor receptor (EGFR) is a member of the ErbB family that
can promote the migration and proliferation of breast cancer cells. Therapies
that target EGFR can promote the dimerization of EGFR with other ErbB receptors,
which is associated with the development of drug resistance. Understanding how
interactions among ErbB receptors alter EGFR biology could provide avenues for
improving cancer therapy. We found that EGFR interacted directly with the CYT1
and CYT2 variants of ErbB4 and the membrane-anchored intracellular domain (mICD).
The CYT2 variant, but not the CYT1 variant, protected EGFR from ligand-induced
degradation by competing with EGFR for binding to a complex containing the E3
ubiquitin ligase c-Cbl and the adaptor Grb2. Cultured breast cancer cells
overexpressing both EGFR and ErbB4 CYT2 mICD exhibited increased migration. With
molecular modeling, we identified residues involved in stabilizing the EGFR
dimer. Mutation of these residues in the dimer interface destabilized the complex
in cells and abrogated growth factor-stimulated cell migration. An exon array
analysis of 155 breast tumors revealed that the relative mRNA abundance of the
ErbB4 CYT2 variant was increased in ER+ HER2- breast cancer patients, suggesting
that our findings could be clinically relevant. We propose a mechanism whereby
competition for binding to c-Cbl in an ErbB signaling heterodimer promotes
migration in response to a growth factor gradient.
PMID- 25140054
TI - Macromolecular assembly of the adaptor SLP-65 at intracellular vesicles in
resting B cells.
AB - The traditional view of how intracellular effector proteins are recruited to the
B cell antigen receptor (BCR) complex at the plasma membrane is based on the
occurrence of direct protein-protein interactions, as exemplified by the
recruitment of the tyrosine kinase Syk (spleen tyrosine kinase) to phosphorylated
motifs in BCR signaling subunits. By contrast, the subcellular targeting of the
cytosolic adaptor protein SLP-65 (Src homology 2 domain-containing leukocyte
adaptor protein of 65 kD), which serves as a proximal Syk substrate, is unclear.
We showed that SLP-65 activation required its association at vesicular
compartments in resting B cells. A module of ~50 amino acid residues located at
the amino terminus of SLP-65 anchored SLP-65 to the vesicles. Nuclear magnetic
resonance spectroscopy showed that the SLP-65 amino terminus was structurally
disordered in solution but could bind in a structured manner to noncharged lipid
components of cellular membranes. Our finding that preformed vesicular signaling
scaffolds are required for B cell activation indicates that vesicles may deliver
preassembled signaling cargo to sites of BCR activation.
PMID- 25140055
TI - Manipulation of receptor oligomerization as a strategy to inhibit signaling by
TNF superfamily members.
AB - Signaling by receptor activator of nuclear factor kappaB (RANK) in response to
its ligand RANKL, which is a member of the tumor necrosis factor (TNF)
superfamily of cytokines, stimulates osteoclast formation and bone resorption.
Thus, this ligand-receptor pair is a therapeutic target for various disorders,
such as osteoporosis and metastasis of cancer to bone. RANKL exists as a
physiological homotrimer, with each monomer recognizing a single molecule of RANK
or the decoy receptor osteoprotegerin (OPG), which inhibits osteoclastogenesis.
We engineered a RANKL protein in which all three monomers of RANKL were encoded
as a single polypeptide chain, which enabled us to independently control receptor
binding at each binding interface. To generate an effective RANK inhibitor, we
used an unbiased forward genetic approach to identify mutations in RANKL that had
a 500-fold increased affinity for RANK but had decreased affinity for the decoy
receptor OPG. Incorporating mutations that blocked receptor binding into this
high-affinity RANKL variant generated a mutant RANKL that completely inhibited
wild-type RANKL-induced osteoclastogenesis in vitro and bone resorption in mice.
Our approach may be generalized to enable the inhibition of other TNF receptor
signaling systems, which are implicated in a wide range of pathological
conditions.
PMID- 25140056
TI - The incidence of secondary vertebral fracture of vertebral augmentation
techniques versus conservative treatment for painful osteoporotic vertebral
fractures: a systematic review and meta-analysis.
AB - BACKGROUND: Percutaneous vertebroplasty (PVP) and balloon kyphoplasty (BKP) are
minimally invasive and effective vertebral augmentation techniques for managing
osteoporotic vertebral compression fractures (OVCFs). Recent meta-analyses have
compared the incidence of secondary vertebral fractures between patients treated
with vertebral augmentation techniques or conservative treatment; however, the
inclusions were not thorough and rigorous enough, and the effects of each
technique on the incidence of secondary vertebral fractures remain unclear.
PURPOSE: To perform an updated systematic review and meta-analysis of the studies
with more rigorous inclusion criteria on the effects of vertebral augmentation
techniques and conservative treatment for OVCF on the incidence of secondary
vertebral fractures. MATERIAL AND METHODS: PubMed, MEDLINE, EMBASE, SpringerLink,
Web of Science, and the Cochrane Library database were searched for relevant
original articles comparing the incidence of secondary vertebral fractures
between vertebral augmentation techniques and conservative treatment for patients
with OVCFs. Randomized controlled trials (RCTs) and prospective non-randomized
controlled trials (NRCTs) were identified. The methodological qualities of the
studies were evaluated, relevant data were extracted and recorded, and an
appropriate meta-analysis was conducted. RESULTS: A total of 13 articles were
included. The pooled results from included studies showed no statistically
significant differences in the incidence of secondary vertebral fractures between
patients treated with vertebral augmentation techniques and conservative
treatment. Subgroup analysis comparing different study designs, durations of
symptoms, follow-up times, races of patients, and techniques were conducted, and
no significant differences in the incidence of secondary fractures were
identified (P > 0.05). No obvious publication bias was detected by either Begg's
test (P = 0.360 > 0.05) or Egger's test (P = 0.373 > 0.05). CONCLUSION: Despite
current thinking in the field that vertebral augmentation procedures may increase
the incidence of secondary fractures, we found no differences in the incidence of
secondary fractures between vertebral augmentation techniques and conservative
treatment for patients with OVCFs.
PMID- 25140057
TI - CT chest and gantry rotation time: does the rotation time influence image
quality?
AB - BACKGROUND: Computed tomography (CT) gantry rotation time is one factor
influencing image quality. Until now, there has been no report investigating the
influence of gantry rotation time on chest CT image quality. PURPOSE: To
investigate the influence of faster gantry rotation time on image quality and
subjective and objective image parameters in chest CT imaging. MATERIAL AND
METHODS: Chest CT scans from 160 patients were examined in this study. All scans
were performed using a single-source mode (collimation, 128 * 0.6 mm; pitch, 1.2)
on a dual-source CT scanner. Only gantry rotation time was modified, while other
CT parameters were kept stable for each scan (120 kV/110 reference mAs). Patients
were divided into four groups based on rotation time: group 1, 1 s/ rotation
(rot); group 2, 0.5 s/rot; group 3, 0.33 s/rot; group 4, 0.28 s/rot. Two blinded
radiologists subjectively compared CT image quality, noise, and artifacts, as
well as radiation exposure, from all groups. For objective comparison, all image
datasets were analyzed by a radiologist with 5 years of experience concerning
objective measurements as well as signal-to-noise ratio (SNR). RESULTS: We found
that faster gantry rotation times (0.28 s/rot and 0.33 s/rot) resulted in more
streak artifacts, image noise, and decreased image quality. However, there was no
significant difference in radiation exposure between faster and slower rotation
times (P > 0.7). CONCLUSION: Faster CT gantry rotation reduces scan time and
motion artifacts. However, accelerating rotation time increases image noise and
streak artifacts. Therefore, a slower CT gantry rotation speed is still
recommended for higher image quality in some cases.
PMID- 25140058
TI - Dilatation of the Virchow-Robin spaces as an indicator of unilateral carotid
artery stenosis: correlation with white matter lesions.
AB - BACKGROUND: Virchow-Robin space (VRS) dilatation is related to many pathologic
conditions, mostly associated with vascular abnormalities. White matter lesions
(WMLs) are commonly seen on brain magnetic resonance imaging (MRI) with advancing
age and generally considered as potential markers for vascular disease. PURPOSE:
To investigate if asymmetric dilatation of VRSs and WMLs are associated with
unilateral internal carotid artery stenosis (ICAS) and to test the relationship
between dilated VRSs and common vascular risk factors. MATERIAL AND METHODS:
Twenty-nine patients (18 men, 11 women; mean age, 68.62 years) with unilateral
ICAS (>=70% carotid stenosis) undergoing carotid endarterectomy were identified
for this Health Insurance Portability and Accountability Act (HIPAA) compliant
prospective study and assessed with brain MRI. Two experienced radiologists
scored VRSs and WMLs and evaluated old infarcts, chronic lacunar infarcts, and
cerebral atrophy. Asymmetry of WML and VRS scores between two cerebral
hemispheres was assessed and associations between VRS scores, WML scores, and
explanatory variables (e.g. age, sex, vascular risk factors, and atrophy) were
tested. RESULTS: In this study, WMLs and basal ganglia VRSs were significantly
greater in the unilateral hemisphere with ICA stenosis than contralateral
hemisphere. Basal ganglia VRSs were associated with WMLs and internal cerebral
atrophy. No association between the severity of VRSs and vascular risk factors
was found. CONCLUSION: ICA stenosis may contribute as a factor in the development
of WMLs and dilatation of VRSs by causing chronic hypoperfusion. VRS dilatation
may be an additional MRI marker of ICAS.
PMID- 25140059
TI - The 25-year genetic era in hypertrophic cardiomyopathy: revisited.
PMID- 25140060
TI - Is the phenotype-genotype relationship necessary to understand cardiomyopathies?
PMID- 25140061
TI - Network biology in medicine and beyond.
PMID- 25140062
TI - TraceRNA: a web application for competing endogenous RNA exploration.
PMID- 25140064
TI - Cardiac cell therapy in nonhuman primates: a significant step toward clinical
translation.
PMID- 25140063
TI - A clinical approach to inherited premature coronary artery disease.
PMID- 25140065
TI - MicroRNA passenger strand: orchestral symphony of paracrine signaling.
PMID- 25140066
TI - Prognostic implications of the systolic to diastolic duration ratio in children
with idiopathic or familial dilated cardiomyopathy.
AB - BACKGROUND: Childhood dilated cardiomyopathy (DCM) carries high morbidity and
mortality. The echocardiographic systolic to diastolic (S:D) duration ratio, an
indicator of global cardiac performance, is elevated in DCM; however, its
prognostic implications have not been investigated in this population. METHODS
AND RESULTS: We investigated systolic and diastolic durations and the resultant
S:D ratio using pulsed tissue Doppler imaging in children with idiopathic or
familial DCM. We studied serial echocardiograms from presentation until the last
follow-up echo. Results were compared with heart rate-matched controls and
between DCM subgroups based on an acute or insidious presentation. The
association between S:D ratio and death or need for transplant was analyzed. All
analyses were adjusted for repeated measures per patient. We studied 200 serial
echocardiograms of 48 children with DCM (7.0+/-6.0 years) and 25 controls.
Adjusted for repeated measures through a compound symmetry covariance structure,
the S:D ratio was higher in DCM patients (-0.425 [0.072]; P<0.001) because of
shortened diastole. A S:D ratio >1.2 at presentation and on serial evaluation was
associated with a hazard ratio of 10.5 (95% confidence interval, 3.9-27.8;
P<0.001) for death or transplant. In combined multivariable analysis, a S:D ratio
>1.2 remained significantly associated with hazard of death/transplant (hazard
ratio, 9.1; P=0.04) after adjustment for ejection fraction (hazard ratio: 2.2 per
-10%; P<0.001). CONCLUSIONS: A high S:D ratio is associated with increased risk
for death or need for transplant in children with DCM across the spectrum of
heart rates and may be a useful prognostic index for serial evaluation of
children with DCM.
PMID- 25140067
TI - Quantification of left ventricular interstitial fibrosis in asymptomatic chronic
primary degenerative mitral regurgitation.
AB - BACKGROUND: The optimum timing of surgery in asymptomatic patients with chronic
severe primary degenerative mitral regurgitation (MR) remains controversial, and
further markers are needed to improve decision-making. There are limited data
that wall stress is increased in MR and may result in ventricular fibrosis. We
investigated the hypothesis that chronic volume overload in MR is a stimulus for
myocardial fibrosis using T1-mapping cardiac MRI. METHODS AND RESULTS: A cross
sectional study of 35 patients (age 60 +/- 14 years) with asymptomatic moderate
and severe primary degenerative MR (mean effective regurgitant orifice area, 0.45
+/- 0.25 cm)(2) with no class I indication for surgery were compared with age and
sex controls. Subjects were studied with cardiopulmonary exercise testing,
echocardiography, and cardiac MRI. Longitudinal and circumferential myocardial
deformation was reduced with MR when left ventricular ejection fraction (67% +/-
10%) and N-terminal pro B Natriuretic peptide (126 [76-428] ng/L) were within the
normal range. Myocardial extracellular volume was increased (0.32 +/- 0.07 versus
0.25 +/- 0.02, P<0.01) and was associated with increased left ventricular end
systolic volume index (r=0.62, P<0.01), left atrial volume index (r=0.41, P<0.05)
but lower left ventricular ejection fraction (r=-0.60, P<0.01), longitudinal
function (mitral annular plane systolic excursion, r=-0.46, P<0.01), and peak VO2
max (r=-0.51, P<0.05). In a multivariable regression model, left ventricular end
systolic volume index and left atrial volume index were independent predictors of
extracellular volume (r(2)=0.42, P<0.01). CONCLUSIONS: Patients with asymptomatic
MR demonstrate a spectrum of myocardial fibrosis associated with reduced
myocardial deformation and reduced exercise capacity. Future work is warranted to
investigate whether left ventricle fibrosis affects clinical outcomes.
PMID- 25140068
TI - Interpolating U.S. Decennial Census Tract Data from as Early as 1970 to 2010: A
Longtitudinal Tract Database.
AB - Differences in the reporting units of data from diverse sources and changes in
units over time are common obstacles to analysis of areal data. We compare common
approaches to this problem in the context of changes over time in the boundaries
of U.S. census tracts. In every decennial census many tracts are split,
consolidated, or changed in other ways from the previous boundaries to reflect
population growth or decline. We examine two interpolation methods to create a
bridge between years, one that relies only on areal weighting and another that
also introduces population weights. Results demonstrate that these approaches
produce substantially different estimates for variables that involve population
counts, but they have a high degree of convergence for variables defined as rates
or averages. Finally the paper describes the Longitudinal Tract Data Base (LTDB),
through which we are making available public-use tools to implement these methods
to create estimates within 2010 tract boundaries for any tract-level data (from
the census or other sources) that are available for prior years as early as 1970.
PMID- 25140069
TI - Relative ion yields in mammalian cell components using C60 SIMS.
AB - Time of flight secondary ion mass spectrometry has been used to better understand
the influence of molecular environment on the relative ion yields of membrane
lipid molecules found in high abundance in a model mammalian cell line, RAW264.7.
Control lipid mixtures were prepared to simulate lipid-lipid interactions in the
inner and outer leaflet of cell membranes. Compared with its pure film, the
molecular ion yields of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1-palmitoyl
2-oleoyl-sn-glycero-3-phosphocholine are suppressed when mixed with 2-dipalmitoyl
sn-glycero-3-phosphocholine. In the mixture, proton competition between 1,2
dioleoyl-sn-glycero-3-phosphocholine, 1-palmitoyl-2-oleoyl-sn-glycero-3
phosphocholine, and 2-dipalmitoyl-sn-glycero-3-phosphocholine led to lower
ionization efficiency. The possible mechanism for ion suppression was also
investigated with 1H and 13C nuclear magnetic resonance spectroscopy. The
formation of a hydroxyl bond in lipid mixtures confirms the mechanism involving
proton exchange with the surrounding environment. Similar effects were observed
for lipid mixtures mimicking the composition of the inner leaflet of cell
membranes. The secondary molecular ion yield of 1-palmitoyl-2-oleoyl-sn-glycero-3
phospho-L-serine was observed to be enhanced in the presence of 1-palmitoyl-2
oleoyl-sn-glycero-3-phosphoethanolamine.
PMID- 25140071
TI - Multi-directional local search.
AB - This paper introduces multi-directional local search, a metaheuristic for multi
objective optimization. We first motivate the method and present an algorithmic
framework for it. We then apply it to several known multi-objective problems such
as the multi-objective multi-dimensional knapsack problem, the bi-objective set
packing problem and the bi-objective orienteering problem. Experimental results
show that our method systematically provides solution sets of comparable quality
with state-of-the-art methods applied to benchmark instances of these problems,
within reasonable CPU effort. We conclude that the proposed algorithmic framework
is a viable option when solving multi-objective optimization problems.
PMID- 25140070
TI - Serum interleukin 17 levels in patients with Crohn's disease: real life data.
AB - The aim of this study was to investigate serum IL17 levels in patients with
Crohn's disease (CD) and to investigate the relationship between serum IL17
levels with disease activity. METHODS: Fifty patients with CD and sex- and age
matched 40 healthy controls were included in the study. The serum IL17 levels,
complete blood count, blood chemistry, erythrocyte sedimentation rate (ESR), and
C-reactive protein (CRP) levels were measured, and Crohn's disease activity was
calculated using Crohn's disease activity index (CDAI). RESULTS: The mean serum
IL17 level of CD patients did not differ from those of healthy controls (P >
0.05). There was no difference between the mean serum IL levels of active CD
patients and of quiescent CD patients (P > 0.05). However, the mean IL17 level of
active patients was lower than of control subjects (P = 0.02). Serum IL17 was not
correlated with inflammatory markers (ESR, CRP, white blood count, platelet
count, and albumin) and CDAI. CONCLUSIONS: Peripheral blood serum IL17 levels of
CD patients were not higher than of healthy controls, and also, serum IL17 level
was not correlated with clinical disease activity. Peripheral IL17 measurement is
not a useful tool for detecting and monitoring Crohn's disease which is
understood to have complex etiopathogenesis.
PMID- 25140072
TI - Informed Consent and Ethical Review in Chinese Human Experimentation: Reflections
on the "Golden Rice Event"
PMID- 25140073
TI - Evaluation of the method of hemostasis after femoral arterial puncture.
AB - [Purpose] This study assessed the advantages and shortcomings of methods for
hemostasis in patients who had received angiography after femoral arterial
puncture using manual, compression device, or a combination of manual compression
and a compression device. In addition, the success rates, complications, etc,
were analyzed. [Subjects and Methods] One hundred and eighty patients who had
undergone angiography after femoral arterial puncture were divided into three
groups according to the method of hemostasis. For group A, immediately after
angiography, an Angio-Seal device was placed in the puncture area and compressed
using a compression device. For group B, after angiography, the puncture area was
compressed with the hands directly. For group C, the puncture area was compressed
using a compression device for approximately 10 min, and the puncture area was
then compressed with the hands. In each group, the following correlations were
analyzed: the time to hemostasis after angiography and gender, the time to
hemostasis of each generation and the hemoglobin value, and platelet value and
the time to hemostasis. [Results] The results showed a similar time to hemostasis
regardless of gender or generation. The correlation between the hemoglobin value,
platelet value, and the time to hemostasis were not significant. Group A showed
the shortest mean time to hemostasis of the three groups (20.37 +/- 8.23 min). No
complications caused by the hemostasis method were detected in group B. Group A
showed the highest incidence of complications caused by hemostasis. [Conclusion]
Overall, hemostasis performed mutually is safe and effective for patients
according to their condition.
PMID- 25140074
TI - Correlation between Intrinsic Patellofemoral Pain Syndrome in Young Adults and
Lower Extremity Biomechanics.
AB - [Purpose] The purpose of this study was to evaluate the correlation between
intrinsic patellofemoral pain syndrome (PFPS) in young adults and lower extremity
biomechanics. [Subjects] This experiment was carried out with sixty (24 men and
32 women), who are normal university students as subjects. [Methods] All subjects
underwent 3 clinical evaluations. For distinguishing the intrinsic PFPS from
controls, we used the Modified Functional Index Questionnaire (MFIQ), Clarke's
test and the Eccentric step test. Based on the results of the tests, subjects who
were classified as positive for 2 more tests were allocated to the bilateral or
unilateral intrinsic PFPS group (n=14), and the others were allocated to the
control group (n=42). These two groups were tested for hamstring tightness, foot
overpronation, and static Q-angle and dynamic Q-angle. These are the four lower
extremity biomechanic, cited as risk factors of patellofemoral pain syndrome.
[Results] The over pronation, static Q-angle and the dynamic Q-angle were not
significantly different between the two groups. However, the hamstring tightness
of the PFPS group was significantly greater than that of the controls.
[Conclusion] We examined individuals for intrinsic patellofemoral pain syndrome
in young adults and lower extremity biomechanics. We found a strong correlation
between intrinsic PFPS and hamstring tightness.
PMID- 25140075
TI - The effect of ground tilt on the lower extremity muscle activity of stroke
patients performing squat exercises.
AB - [Purpose] The purpose of this study was to determine the effect of ground tilt on
the lower extremity muscle activity of stroke patients performing squat
exercises. [Subjects] Fifteen hemiparetic patients volunteered to participate in
this study. [Methods] The subjects performed squat exercises at three different
ground tilt angles: 15 degrees plantar flexion, a neutral position, and 15
degrees dorsiflexion. A surface electromyogram (sEMG) was used to record the
electromyographic activities of the leg extensor muscle in the vastus lateralis
(VL), vastus medialis (VM), gastrocnemius lateralis (GL), and gastrocnemius
medialis (GM). The sEMG activity was analyzed using a one-way repeated measures
ANOVA and a post hoc Bonferroni correction. [Results] The results of this study
are summarized as follows. Significant differences were noted for the VL and the
GL when the angle of the ankle joint was between the 15 degrees plantar flexion
and neutral positions during squat exercises involving the VL and when the angle
of the ankle joint was between the neutral position and 15 degrees dorsiflexion
during squat exercises involving the VM. [Conclusion] In this study, sEMG showed
that the VL and GL changed significantly during squat exercises according to the
ground tilt angle of hemiparetic patients. Therefore, squat exercises with
different ground tilt angles can be used to improve VL and GL strength.
PMID- 25140076
TI - Effect of the Frequency and Duration of Land-based Therapeutic Exercise on Pain
Relief for People with Knee Osteoarthritis: A Systematic Review and Meta-analysis
of Randomized Controlled Trials.
AB - [Purpose] This study aimed to investigate the influence of land-based exercise
frequency and duration on pain relief for people with knee osteoarthritis (OA).
[Subjects and Methods] The systematic review included randomized controlled
trials that investigated this influence, which were identified by searches of
PubMed, the Cochrane Central Register of Controlled Trials, the Physiotherapy
Evidence Database, and the Cumulative Index to Nursing and Allied Health
Literature. The exercise groups in the identified trials were categorized
according to their type, frequency, and duration of exercise, and subgroup
analyses were performed. [Results] Data integration of 17 studies (23 exercise
groups) revealed a significant effect and a medium effect size. In subgroups
involving strengthening exercise programs of >=9 weeks duration, heterogeneity
was found between subjects who performed up to 3 sessions/week and those who
performed >=4 sessions/week. In subgroups involving strengthening exercise
programs of up to 3 sessions/week, there was heterogeneity between subjects who
exercised for up to 8 weeks and those who exercised for >=9 weeks. Heterogeneity
was not confirmed in aerobic exercise subgroups. [Conclusion] Differences in
exercise frequency and duration influence pain relief in effects of strengthening
exercises but do not influence the effect size of aerobic exercise for people
with knee OA.
PMID- 25140077
TI - Effect of gross motor group exercise on functional status in chronic stroke: a
randomized controlled trial.
AB - [Purpose] The aim of this study was to understand the effects of task-oriented
gross motor group exercise based on motor development on chronic stroke patients'
joint, bone, muscle, and motor functions and activities of daily living.
[Subjects] Twenty-eight stroke patients hospitalized at P municipal nursing
facility for the severely handicapped were randomly assigned to the gross motor
group exercise group (experimental group, n=14) or the control group (n=14).
[Methods] The two groups performed morning exercise led by a trainer for 30
minutes a day, 5 times a week for 6 weeks in total. The experimental group
performed a gross motor group exercise in addition to this exercise for 50
minutes a day, 3 times a week for 6 weeks in total. Before the experiment, all
subjects were measured with the Modified Barthel Index (MBI) and for their
neuromuscular skeletal and motor-related functions according to the International
Classification of Functioning, Disability and Health. [Results] Significant
improvements were found in the experimental group's neuromusculoskeletal and
motor-related functions and MBI test, except for the stability of joint
functions. The control group showed no significant difference from the initial
evaluation. [Conclusion] The gross motor group exercise based on motor
development is recommended for chronic stroke patients with severe handicaps.
PMID- 25140078
TI - Effects of the nerve mobilization technique on lower limb function in patients
with poststroke hemiparesis.
AB - [Purpose] The purpose of the study was to determine the effects of a sciatic
nerve mobilization technique on improvement of lower limb function in patient
with poststroke hemiparesis. [Subjects] Twenty- two stroke patients participated
in this study. [Methods] They were randomly selected based on selection criteria
and divided into two groups. In the subject group (n=10), sciatic nerve
mobilization with conventional physical therapy was applied to patients. In the
control group (n=10), only conventional physical therapy was applied to stroke
patients. [Results] There were significant differences between the two groups in
pressure, sway, total pressure, angle of the knee joint, and functional reaching
test results in the intervention at two weeks and at four weeks. [Conclusion] The
present study showed that sciatic nerve mobilization with conventional physical
therapy was more effective for lower limb function than conventional physical
therapy alone in patient with poststroke hemiparesis.
PMID- 25140079
TI - A Pilot Study on Pain and the Upregulation of Myoglobin through Low-frequency and
High-amplitude Electrical Stimulation-induced Muscle Contraction.
AB - [Purpose] It is well known that, in both in vivo and in vitro tests, muscle
fatigue is produced by severe exercise, electrical stimulation, and so on.
However, it is not clear whether or not low-frequency and high-amplitude
modulation specifically affects serum myoglobin or urine myoglobin. The purpose
of the present study was to determine the effect of low-frequency and high
amplitude modulation on serum myoglobin and urine myoglobin. [Methods] The study
used whole blood samples and urine produced over 24 hours from the thirteen
healthy subjects. [Results] There was a significant increase in serum myoglobin
following electrical stimulation at a frequency of 10 Hz compared with the
control group. Furthermore, within 24 hours, urine myoglobin also showed a
significant increase for the test volunteers subjected to electrical stimulation
at the 10 Hz frequency compared with the control group. However, there were no
significant differences in the concentrations of hematologic results in subjects
treated with electrical stimulation. [Conclusion] These results suggest that
increased myoglobin related to muscle fatigue from electrical stimulation,
particularly with a current of 10 Hz combined with a high-amplitude, may be
partially related to increased muscle damage.
PMID- 25140080
TI - Effect of Weight-bearing Therapeutic Exercise on the Q-angle and Muscle Activity
Onset Times of Elite Athletes with Patellofemoral Pain Syndrome: A Randomized
Controlled Trial.
AB - [Purpose] The purpose of this study was to determine the effect of a weight
bearing therapeutic exercise program for elite athletes diagnosed as having
patellofemoral pain syndrome (PFPS). [Subjects] The subjects were 34 elite
athletes from the Seoul T Center. They were randomly allocated to three groups:
an elastic band exercise group (EBG), a sling exercise group (SEG), or a control
group (CG). [Methods] Therapeutic exercises were performed 3 times a week for 8
weeks. The visual analogue scale (VAS) hamstring length, and static and dynamic Q
angles were used to test the exercise effect of the exercises, as well as the
onset time of electromyographic activity of vastus medialis oblique (VMO) and
vastus lateralis (VL). [Results] Decrease of the dynamic Q-angle in EBG was
significant and significantly greater than that in CG. The decrease in VAS in SEG
was significant and significantly greater than that in CG. There were significant
differences in the VL and VMO activity onset times in SEG between pre- and post
test, and their differences between pre- and post-test were also significantly
different. [Conclusion] Weight-bearing therapeutic exercise is hoped that
clinicians will use this information for better implementation of effective
exercise methods for elite athletes with PFPS.
PMID- 25140081
TI - Reliability of pinch strength testing in elderly subjects with unilateral thumb
carpometacarpal osteoarthritis.
AB - [Purpose] The aim of this study was to examine the test-retest reliability of
pinch strength testing in elderly subjects with thumb CMC OA. [Subjects and
Methods] A total of 27 patients with unilateral right-thumb CMC OA (mean +/- SD
age: 81.3 +/- 4.7 years) were recruited. Each patient performed three pain-free
maximal isometric contractions on each hand on two occasions, one week apart.
Three different measurements were taken: tip, tripod, and key pinch strength.
Intraclass correlation coefficient (ICC), standard error of measurement (SEM),
and 95% limits of agreement (LOA) calculations were performed. [Results] Test
retest reliability of measurements of tip, tripod, and key pinch strength was
excellent for the affected side (ICC=0.93, 0.96, and 0.99) and the contralateral
thumb (ICC=0.91, 0.92, and 0.94). [Conclusions] The present results indicate that
maximum pinch strength can be measured reliably using the Pinch Gauge
Dynamometer, in patients with thumb CMC OA, which enables its use in research and
in the clinic to determine the effect of interventions on improving pinch
strength.
PMID- 25140082
TI - Accelerometer and gyroscope based gait analysis using spectral analysis of
patients with osteoarthritis of the knee.
AB - [Purpose] A wide variety of accelerometer tools are used to estimate human
movement, but there are no adequate data relating to gait symmetry parameters in
the context of knee osteoarthritis. This study's purpose was to evaluate a 3D
kinematic system using body-mounted sensors (gyroscopes and accelerometers) on
the trunk and limbs. This is the first study to use spectral analysis for data
post processing. [Subjects] Twelve patients with unilateral knee osteoarthritis
(OA) (10 male) and seven age-matched controls (6 male) were studied. [Methods]
Measurements with 3-D accelerometers and gyroscopes were compared to video
analysis with marker positions tracked by a six-camera optoelectronic system
(VICON 460, Oxford Metrics). Data were recorded using the 3D-kinematic system.
[Results] The results of both gait analysis systems were significantly
correlated. Five parameters were significantly different between the knee OA and
control groups. To overcome time spent in expensive post-processing routines,
spectral analysis was performed for fast differentiation between normal gait and
pathological gait signals using the 3D-kinematic system. [Conclusions] The 3D
kinematic system is objective, inexpensive, accurate and portable, and allows
long-term recordings in clinical, sport as well as ergonomic or functional
capacity evaluation (FCE) settings. For fast post-processing, spectral analysis
of the recorded data is recommended.
PMID- 25140083
TI - Immediate Effect of Postural Insoles on Gait Performance of Children with
Cerebral Palsy: Preliminary Randomized Controlled Double-blind Clinical Trial.
AB - [Purpose] Improved gait efficiency is one of the goals of therapy for children
with cerebral palsy (CP). Postural insoles can allow more efficient gait by
improving biomechanical alignment. The aim of the present study was to assess the
effect of postural insoles on gait performance of children with CP classified as
levels I or II of the Gross Motor Function Classification System (GMFCS).
[Subjects and Methods] the study was a randomized controlled double-blind
clinical trial. After meeting the legal aspects and the eligibility criteria, 10
children between four and 12 years old were randomly divided into a two groups: a
control group (n=5), and an experimental group (n=5). Children in the control
group used a placebo insoles, and children in the experimental group used
postural insoles. Evaluation consisted of three-dimensional gait analysis under
three conditions: barefoot, shoes without insoles and shoes with postural insoles
or shoes with placebo insoles. [Results] Regarding the immediate effects of
insole use, significant improvements in gait velocity and cadence were observed
in the experimental group in comparison to the control group. [Conclusion] The
use of postural insoles led to improvements in gait velocity and cadence of the
children with cerebral palsy classified as levels I or II of the GMFCS.
PMID- 25140085
TI - Effect of smart phone use on dynamic postural balance.
AB - [Purpose] The present study investigated what kind of effect smart phone use has
on dynamic postural balance. [Subjects] The study subjects were 30 healthy
students in their 20's who were recruited from a University in Busan, Korea.
[Methods] The present experiment was quasi-experimental research which measured
the postural balance (Biodex) of subjects while they sent text messages via smart
phones in the standing position with the eyes open, and while they used two-way
SNS. [Results] There were significant differences between standing and the dual
task situations. Among dual tasks using smart phones, SNS using situations showed
the highest instability. [Conclusion] The use of smart phones in less stable
conditions such as while walking or in moving vehicles should be discouraged.
PMID- 25140084
TI - Comparison of upper extremity motor recovery of stroke patients with actual
physical activity in their daily lives measured with accelerometers.
AB - [Purpose] This study compared the upper extremity recovery of stroke patients
with the amount of their upper extremity use in real life as measured by
accelerometers. [Subjects] Forty inpatients who had had a stroke were recruited.
[Methods] The subjects were divided into two groups by the Fugl-Meyer Assessment
of Motor Function (FMA) score, a moderately recovered group and a well recovered
group. The amount of upper extremity physical activity and its ratio in daily
time periods were analyzed for the affected and unaffected sides. [Results] The
well recovered group showed significantly higher affected arm use and use ratio
than the moderately recovered group in all time periods. [Conclusion] The upper
extremity recovery level of the affected side is similar to the physical activity
level according to the amount of upper extremity physical activity in actual life
measured with an accelerometer. Overuse of the normal side regardless of the
recovery level of upper extremity proves the International Classification of
Functioning (ICF) concept of differentiating between capacity and performance,
and rehabilitation treatments should focus on improving performance.
PMID- 25140086
TI - Effects of neuromobilization maneuver on clinical and electrophysiological
measures of patients with carpal tunnel syndrome.
AB - [Purpose] The aim of this study was to investigate the efficacy of
neuromobilization combined with routine physiotherapy in patients with carpal
tunnel syndrome through subjective, physical, and electrophysiological studies.
[Subjects and Methods] Twenty patients with carpal tunnel syndrome (totally 32
hands) were assigned two groups: treatment and control groups. In both groups,
patients received the routine physiotherapy. In addition to the routine
physiotherapy, patients in the treatment group received neuromobilization. The
symptoms severity scale, visual analogue scale, functional status scale, Phalen's
sign, median nerve tension test, and median nerve distal sensory and motor
latency were assessed. [Results] There were significant improvements in the
symptoms severity scale, visual analogue scale, median nerve tension test, and
Phalen's sign in both groups. However, the functional status scale and median
nerve distal motor latency were significantly improved only in the treatment
group. [Conclusion] Neuromobilization in combination with routine physiotherapy
improves some clinical findings more effectively than routine physiotherapy.
Therefore, this combination can be used as an alternative effective non-invasive
treatment for patients with carpal tunnel syndrome.
PMID- 25140087
TI - Effects of Pelvic Belt on Hip Extensor Muscle EMG Activity during Prone Hip
Extension in Females with Chronic Low Back Pain.
AB - [Purpose] This study assessed the effects of a pelvic belt (PB) on the
electromyography (EMG) activity of the elector spinae (ES), gluteus maximus (GM),
and biceps femoris (BF) in females with chronic low back pain (CLBP) during prone
hip extension (PHE). [Subjects] Twenty female with CLBP were recruited. Surface
EMG data were collected from the ES, GM, and BF muscles during a PHE task.
[Results] The EMG activity in the ES bilaterally, and the right GM decreased
significantly when a PB was applied compared with when a PB was not applied.
[Conclusion] This suggests that a PB is effective for altering the activation
pattern of the hip extensor muscles in females with CLBP during PHE.
PMID- 25140088
TI - Tai Chi Exercise can Improve the Obstacle Negotiating Ability of People with
Parkinson's Disease: A Preliminary Study.
AB - [Purpose] The purpose of this study was to examine the effects of Tai Chi (TC)
based exercise on dynamic postural control during obstacle negotiation by
subjects with mild or moderate Parkinson's disease (PD). [Subjects] Twelve
subjects (mean age, 65.3+/-6.1 years) diagnosed with idiopathic PD were enrolled
for this study. [Methods] All the subjects were tested a week before and 12 weeks
after the initiation of the TC exercise. In the test, they were instructed to
negotiate an obstacle from the position of quiet stance at a normal speed. They
were trained with TC exercise that emphasized multidirectional shift in weight
bearing from bilateral to unilateral support, challenging the postural stability,
three times per week for 12 weeks. Center of pressure (COP) trajectory variables
before and after TC exercise were measured using two force plates. [Results] A
comparison of the results between pre- and post-intervention showed a
statistically significant improvement in anteroposterior and mediolateral
displacement of COP. [Conclusion] Twelve weeks of TC exercise may be an effective
and safe form of stand-alone behavioral intervention for improving the dynamic
postural stability of patients with PD.
PMID- 25140089
TI - Effects of visual display terminal works on cervical movement pattern in patients
with neck pain.
AB - [Purpose] This study examined changes in the onset of neck movement in young
adults with and without mild neck pain (MNP) during visual display terminal (VDT)
work. [Subjects] Ten control subjects and 10 subjects with MNP who were VDT
workers were recruited. The upper (UC) and lower cervical (LC) spine angles in
the sagittal plane were collected using an ultrasound-based motion analysis
system during VDT work for 5 min. [Results] The MNP group had faster movement
initiation in the UC and LC compared with the control group during VDT work.
[Conclusion] These findings suggest that young adults with MNP should be cautious
when performing VDT work while sitting.
PMID- 25140090
TI - Effects of Low-intensity Pulsed Ultrasound and Cryotherapy on Recovery of Joint
Function and C-reactive Protein Levels in Patients after Total Knee Replacement
Surgery.
AB - [Purpose] We investigated the effect of low-intensity pulsed ultrasound and
cryotherapy on joint function recovery and C-reactive protein (CRP) levels of
patients with total knee replacement. [Subjects] Forty-six patients with total
knee replacement were recruited and allocated to either low-intensity pulsed
ultrasound therapy (n=15), cryotherapy (n=15), or a combination of both (n=16).
Therapy was administered once a day, 5 times a week for 3 weeks. To determine
functional joint recovery and reduction of inflammation, changes in the Korean
Western Ontario and McMaster Universities Arthritis Index (K-WOMAC), range of
motion (ROM), and CRP were assessed postsurgically and four times over a 3-week
period. Using one-way analysis of variance (ANOVA), homogeneity tests were
performed based on participants' general characteristics. To recognize changes in
time-variant K-WOMAC, ROM, and CRP values between groups, repeated measures ANOVA
was performed, and Tukey's test was used for post-test analysis. Values at
alpha=0.05 were considered significant. [Results] We found a difference between
groups and times, and the group that received the combined therapies showed
greater changes in outcomes than the group that received low-intensity pulsed
ultrasound therapy alone. [Conclusion] Applying both low-intensity pulsed
ultrasound and cryotherapy can relieve inflammation and enhance joint function in
patients who undergo total knee replacement.
PMID- 25140091
TI - Changes in pain, dysfunction, and grip strength of patients with acute lateral
epicondylitis caused by frequency of physical therapy: a randomized controlled
trial.
AB - [Purpose] The purpose of this study was to investigate the changes in pain,
dysfunction, and grip strength of patients with acute lateral epicondylitis and
to suggest the appropriate treatment frequency and period. [Subjects] The
subjects were divided into three: 2 days per week group (n=12), 3 days per week
group (n=15), and 6 days per week group (n=13). [Methods] All groups received
conventional physical therapy for 40 minutes and therapeutic exercises for 20
minutes per session during 6 weeks. The outcome measurements were the visual
analogue scale (VAS), Patient-Rated Tennis Elbow Evaluation (PRTEE), and grip
strength. [Results] The results of this study were as follows: at 3 weeks, there
were no significant differences in VAS and PRTEE in the 3 groups, but at 6 weeks,
6 days per week group significantly decreased these two outcomes. Grip strength
was significantly increased in 3 and 6 days per week groups at 6 weeks.
[Conclusion] In conclusion, physical therapy is needed 3 days per week for 3
weeks in patients with acute lateral epicondylitis. After 3 weeks, 6 days per
week is the most effective treatment frequency.
PMID- 25140092
TI - Difference in the Effect of Outpatient Pulmonary Rehabilitation Due to Variation
in the Intervention Frequency: Intervention Centering on Home-based Exercise.
AB - [Purpose] The purpose of this study was to investigate differences in effects
caused by variation in the intervention frequency of outpatient pulmonary
rehabilitation, in terms of the pulmonary function, lower-limb muscle strength,
exercise tolerance, and quality of life (QOL). [Subjects and Methods] A total of
36 patients with mild to severe chronic obstructive pulmonary disease (COPD) were
studied. These patients were all men over the age of 40 who did not require
assistance for activities of daily living (ADL). Groups undergoing intervention
once a month (M1 group) and once a week (W1 group) were compared in terms of the
effects of outpatient pulmonary rehabilitation for a period of 12 weeks.
Intervention during this time included supervised and home-based exercise.
[Results] Comparison of before and after intervention revealed that the rate of
change in the W1 group was significantly higher than that in the M1 group in
terms of the QOL, lower-extremity muscle strength, and 6-minute walking distance.
[Conclusion] Outpatient pulmonary rehabilitation programs yielded greater
improvements in the W1 group than in the M1 group in terms of the QOL and
exercise tolerance.
PMID- 25140093
TI - Comparison of the Tibialis Anterior and Soleus Muscles Activities during the Sit
to-stand Movement with Hip Adduction and Hip Abduction in Elderly Females.
AB - [Purpose] The purpose of this study was to compare the activation of the tibialis
anterior (TA) and soleus (SOL) muscles during the sit-to-stand (STS) task with
hip adduction and hip abduction in elderly females. [Subjects] We recruited 16
healthy elderly females with no pain in the knee joint and no other orthopedic
problems of the lower limbs. [Methods] The activities of the dominant lower
extremity muscles were measured using a wireless electromyography (EMG) system.
Subjects then performed a total of nine STS trials, including three trials each
for hip adduction, hip abduction, and natural STS tasks. [Results] In the pre-
thigh-off (TO) phase, the normalized EMG data of the TA muscle increased
significantly when the STS task was performed with hip adduction compared with
hip abduction. In the post-TO phase, the normalized EMG data of the TA muscle
showed a significant increase during the STS task with hip adduction compared
with hip abduction. Additionally, the normalized EMG data of the SOL muscle
increased significantly when the STS task was performed with hip adduction
compared with hip abduction. [Conclusion] Therefore, the STS movement with hip
adduction poses a greater challenge for balance control, indicating that certain
elderly individuals would have difficulty in executing an abrupt adjustment in
their dynamic postural stability during the STS movement.
PMID- 25140094
TI - The Effects of Stretching with Lumbar Traction on VAS and Oswestry Scales of
Patients with Lumbar 4-5 Herniated Intervertebral Disc.
AB - [Purpose] This study investigated the effect of stretching with lumbar traction
on VAS and Oswestry scale scores of lumbar 4-5 herniated intervertebral disc
(HIVD) patients. [Subjects] We recruited 20 lumbar 4-5 HIVD patients. [Methods]
We performed stretching with lumbar traction for lumbar 4-5 HIVD patients during
4 weeks. The VAS and Oswestry scales were measured before and 4 weeks after the
intervention. [Results] The results showed a significant decrease in VAS scale
scores for stretching with lumbar traction in lumbar 4-5 HIVD patients, from 18+/
1.29 to 2.1+/-1.35. The Oswestry scale scores also decreased significantly, from
20.35+/-2.01 to 3.5+/-2.84, after stretching with lumbar traction. [Conclusion]
Thus, we suggest stretching with lumbar traction for lumbar 4-5 HIVD patients.
PMID- 25140095
TI - Peak torque and average power at flexion/extension of the shoulder and knee when
using a mouth guard in adults with mild midline discrepancy.
AB - [Purpose] This study was conducted to investigate the changes in torque and power
during flexion and extension of the shoulder and the knee joints caused by
midline correction using mouth guards made from different materials in adults
with mild midline discrepancy. [Subjects] The subjects of this study were males
(n=12) in their 20s who showed a 3-5 mm difference between the midlines of the
upper and lower teeth but had normal masticatory function. [Methods] The torque
and average power of the lower limb and upper limb were measured during flexion
and extension according to various types of mouth guard. [Results] There were
significant differences in relative torque and average power between three
conditions (no mouth guard, soft-type mouth guard, and hard-type mouth guard) at
shoulder flexion and extension. There were no significant differences in relative
torque and average power between the three conditions at knee flexion and
extension. [Conclusions] These results suggest that use of a mouth guard is a
method by which people with a mild midline discrepancy can improve the stability
of the entire body.
PMID- 25140096
TI - The Effects of Lower Extremity Angle According to Heel-height Changes in Young
Ladies in Their 20s during Gait.
AB - [Purpose] The purpose of this study was to compare the effects of heel-height
changes on the low joint angles of the lower extremities of women in their 20s
during gait. [Subjects and Methods] Qualisys Track Manager Software ver. 2.8
(Qualisys, Sweden) was used to perform measurements on 14 female university
students in their 20s. To measure movements, the subjects were asked to walk
while wearing high-heeled shoes and reflective stickers on their hip joints, knee
joints, and ankle joints, the changes in joint angles were measured at heel
strike, foot flat, and toe off. [Results] Analysis of the amount of change
according to heel height changes during gait showed that the angle of the hip
joints was reduced with an increase in heel-height. Although the changes were not
significant, the angle of the knee joints was reduced during heel strike, foot
flat, and midstance, and it was increased during toe off. In contrast, the angle
of the ankle joints was increased by a significant amount during heel strike,
foot flat, midstance, and toe off. [Conclusions] During gait with high heels, the
movements of the lower extremities of women in their 20s were reduced
significantly with an increase in heel height. Therefore, it is concluded that
the restrictions on gait can only be reduced by wearing low-heeled shoes.
PMID- 25140097
TI - Anaerobic Threshold and Salivary alpha-amylase during Incremental Exercise.
AB - [Purpose] The purpose of this study was to clarify the validity of salivary alpha
amylase as a method of quickly estimating anaerobic threshold and to establish
the relationship between salivary alpha-amylase and double-product breakpoint in
order to create a way to adjust exercise intensity to a safe and effective range.
[Subjects and Methods] Eleven healthy young adults performed an incremental
exercise test using a cycle ergometer. During the incremental exercise test,
oxygen consumption, carbon dioxide production, and ventilatory equivalent were
measured using a breath-by-breath gas analyzer. Systolic blood pressure and heart
rate were measured to calculate the double product, from which double-product
breakpoint was determined. Salivary alpha-amylase was measured to calculate the
salivary threshold. [Results] One-way ANOVA revealed no significant differences
among workloads at the anaerobic threshold, double-product breakpoint, and
salivary threshold. Significant correlations were found between anaerobic
threshold and salivary threshold and between anaerobic threshold and double
product breakpoint. [Conclusion] As a method for estimating anaerobic threshold,
salivary threshold was as good as or better than determination of double-product
breakpoint because the correlation between anaerobic threshold and salivary
threshold was higher than the correlation between anaerobic threshold and double
product breakpoint. Therefore, salivary threshold is a useful index of anaerobic
threshold during an incremental workload.
PMID- 25140098
TI - The Effect of a PNF Technique Program after Mastectomy on Lymphedema Patients'
Depression and Anxiety.
AB - [Purpose] This study was conducted to examine the effects of exercises applied
with PNF techniques performed for 30 minutes per session, three times per week,
after receipt of radiation therapy following mastectomy on depression and anxiety
in patients diagnosed with lymphedema and to prepare basic data for creation of
self-directed exercise programs for lymphedema patients that will enable them to
perform exercises within the range of no pain. [Methods] The subjects of this
study were 45 patients selected from among those diagnosed with breast cancer who
showed lymphedema after anti-cancer therapy following mastectomy. [Results] The
Beck depression score changed significantly during the five assessment periods
however, there was no significant difference between the treatment groups. Post
hoc analyses revealed that there was significant improvement in the Beck
depression score from 4 weeks in all three groups. The interaction between group
and time was also statistically significant. [Conclusion] In conclusion, PNF
techniques helped to improve the depression and anxiety rates. Four weeks after
the start of therapy, PNF techniques Depression and anxiety to create a greater
degree of decline was on display.
PMID- 25140100
TI - The Change in Knee Angle during the Gait by Applying Elastic Tape to the Skin.
AB - [Purpose] The aim of this study was to verify how the application of elastic tape
to the anterior surface of the thigh changes the knee angle pattern during gait.
[Subjects] The subjects were 10 people who showed an abnormal knee angle change
pattern during usual walking. They did not show the so-called double knee action.
[Methods] Subjects were asked to walk as usual, and then to walk with elastic
tape attached to the anterior surface of the thigh. The knee angle was measured
during gait with an electronic goniometer. We graphed the temporal changes of the
knee angle and compared them with the normal gait pattern. [Results] The knee
angle gait pattern of six of the 10 subjects improved after application of the
tape and became like a normal gait pattern. The changes in the knee angle
resulted from a stimulus via the skin, rather than voluntary muscular adjustment,
suggesting that the changes may have originated due to differences in reflexive
tensile strength. [Conclusion] In normal speed gait, it is suggested that the
knee angle was altered such that it exhibited a normal pattern by applying
elastic tape to the anterior surface of the thigh. We suspect that application of
the elastic tape may change the muscle tonus.
PMID- 25140099
TI - Influence of motor imagery of isometric opponens pollicis activity on the
excitability of spinal motor neurons: a comparison using different muscle
contraction strengths.
AB - [Purpose] This study aimed to determine the differences in the excitability of
spinal motor neurons during motor imagery of a muscle contraction at different
contraction strengths. [Methods] We recorded the F-wave in 15 healthy subjects.
First, in a trial at rest, the muscle was relaxed during F-wave recording. Next,
during motor imagery, subjects were instructed to imagine maximum voluntary
contractions of 10%, 30%, and 50% while holding the sensor of a pinch meter, and
F-waves were recorded for each contraction. F-waves were recorded immediately and
at 5, 10, and 15 min after motor imagery. [Results] Both persistence and F/M
amplitude ratios during motor imagery under maximum voluntary contractions of
10%, 30%, and 50% were significantly higher than that at rest. In addition,
persistence, F/M amplitude ratio, and latency were similar during motor imagery
under the three muscle contraction strengths. [Conclusion] Motor imagery under
maximum voluntary contractions of 10%, 30%, and 50% can increase the excitability
of spinal motor neurons. The results indicated that differences in muscle
contraction strengths during motor imagery are not involved in changes in the
excitability of spinal motor neurons.
PMID- 25140101
TI - The effects of elbow joint angle changes on elbow flexor and extensor muscle
strength and activation.
AB - [Purpose] This research investigated the relationship between elbow joint angle
and elbow flexor and extensor strength and activation, taking into consideration
the length-tension tension curve of the muscle. [Subjects] There were 30 research
subjects in total, 15 male and 15 female college students from Busan S University
who had no functional disabilities that might affect measurement of muscle
strength and muscle activation, and none had they experienced any damage in their
upper extremities or hands. [Methods] The elbow joint angles were positioned at
angles of 56 degrees , 70 degrees and 84 degrees , and then muscle strength and
activation were compared. Repeated measures ANOVA was used for statistical
analysis, and the paired t-test was used to identify the difference between each
angle. We used the SPSS for windows (ver. 21.0) statistical software and a
significance level of alpha=0.05. [Results] The results showed that muscle
strength and activation of the biceps was highest when the joint was placed at 56
degrees . On the other hand, for the triceps, the result was highest when the
joint angle was placed at 84 degrees . [Conclusion] The tests confirmed that
muscle strength and activation were highest at the joint angle at which the
muscle was stretched to 20% more than the resting position in concentric
contraction.
PMID- 25140102
TI - Effect of whole body vibration exercise in the horizontal direction on balance
and fear of falling in elderly people: a pilot study.
AB - [Purpose] The purpose of the present study was to investigate the effects of
whole body vibration exercise in the horizontal direction on balance and fear of
falling in the elderly. [Methods] This study was a case series of 17 elderly
individuals. Participants performed whole body vibration exercise in the
horizontal direction using a whole body vibration device for 15 minutes a day, 3
times a week, for 6 weeks. At baseline and after the 6-week intervention, balance
was measured using the Berg Balance Scale and Timed Up and Go test, and fear of
falling was assessed using the Falls Efficacy Scale. [Results] After the
intervention, significant improvements from baseline values in the Berg Balance
Scale, Timed Up and Go test, and Falls Efficacy Scale were observed in the study
participants. [Conclusion] Elderly individuals who performed whole body vibration
exercise in the horizontal direction showed significant improvements in balance
and fear of falling. However, the observed benefits of whole body vibration
exercise in the horizontal direction need to be confirmed by additional studies.
PMID- 25140103
TI - Relationship between Sympathetic Skin Responses and Auditory Hypersensitivity to
Different Auditory Stimuli.
AB - [Purpose] Auditory hypersensitivity has been widely reported in patients with
autism spectrum disorders. However, the neurological background of auditory
hypersensitivity is currently not clear. The present study examined the
relationship between sympathetic nervous system responses and auditory
hypersensitivity induced by different types of auditory stimuli. [Methods] We
exposed 20 healthy young adults to six different types of auditory stimuli. The
amounts of palmar sweating resulting from the auditory stimuli were compared
between groups with (hypersensitive) and without (non-hypersensitive) auditory
hypersensitivity. [Results] Although no group * type of stimulus * first stimulus
interaction was observed for the extent of reaction, significant type of stimulus
* first stimulus interaction was noted for the extent of reaction. For an 80 dB
6,000 Hz stimulus, the trends for palmar sweating differed between the groups.
For the first stimulus, the variance became larger in the hypersensitive group
than in the non-hypersensitive group. [Conclusion] Subjects who regularly felt
excessive reactions to auditory stimuli tended to have excessive sympathetic
responses to repeated loud noises compared with subjects who did not feel
excessive reactions. People with auditory hypersensitivity may be classified into
several subtypes depending on their reaction patterns to auditory stimuli.
PMID- 25140104
TI - Is There Any Relationship between Joint Destruction and Carotid Intima-media
Thickness in Patients with Rheumatoid Arthritis?
AB - [Purpose] The purpose of this study was to investigate the possible relationship
between joint destruction and carotid intima-media thickness in patients with
rheumatoid arthritis. [Subjects and Methods] Thirty-four RA patients and 31
healthy controls were enrolled in this study. The disease activity for 28 joints
was recorded for each patient using the erythrocyte sedimentation rate
(DAS28ESR), a visual analog scale (VAS0-10 cm), and a disability index, the
health assessment questionnaire (HAQ). X-ray imagesof the patients were scored
according to the modified Sharp/van der Heijde method, and the common carotid
intimal medial thickness (CIMT) was automatically measured with software using
high-resolution Doppler ultrasound. [Results] Contrary to our hypothesis, the
modified total Sharp score (mTSS) and CIMT were not significantly associated. The
erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels of the
RA patients and the right CIMT, left CIMT, and mean CIMT scores were
significantly elevated. Positive correlation was detected between the mean CIMT
score and age, CRP levels, LDL concentration and triglycerides (TG) level. In the
regression model, where the mean CIMT was the independent variable and age, CRP,
LDL, and TG were dependent variables, age was found to be an independent
predictor of CIMT. [Conclusions] Patients suffering from RA require close
monitoring for cardiovascular risks, and the comorbidity of age-related
cardiovascular disease should not be overlooked.
PMID- 25140106
TI - The effects of aerobic exercise and strengthening exercise on pain pressure
thresholds.
AB - [Purpose] We assessed the effects of aerobic exercise and strengthening exercise
on pain pressure thresholds (PPTs) over time. [Subjects and Methods] Fifteen
healthy participants were recruited and randomly divided into 3 groups: aerobic
exercise, strengthening exercise, and control. The subjects in the aerobic group
walked on a treadmill for 40 min at 6.5 km/h. The subjects in the strength group
performed circuit training that included bench press, lat pull down, biceps curl,
triceps extension, and shoulder press based on the perceived exertion for 40 min.
The subjects in the control group rested without any exercise in a quiet room for
40 min. The PPTs of 5 potential muscle trigger points before exercise, and
immediately after 10 and 40 min of exercise or rest were measured using an
electronic algometer (JTECH Medical, USA). The Friedman's, Kruskal-Wallis, and
Mann-Whitney tests were performed using SPSS 18.0 (IBM, Korea). [Results] The
PPTs of all subjects decreased after 10 min of exercise, but the difference was
not statistically significant. The PPTs of the control group decreased after 40
min. Furthermore, the PPTs of 3 muscles increased after 40 min of aerobic
exercise and of 6 muscles after 40 min of strengthening exercise. No significant
difference in PPTs was noted among the groups. [Conclusion] The results show that
40 min is a more appropriate exercise time, although the efficacy of controlling
pain did not differ between strengthening exercise and aerobic exercise.
PMID- 25140105
TI - Functional Capacity of Oldest Old Living in a Long-stay Institution in Rio De
Janeiro, Brazil.
AB - [Purpose] A significant increase in the number of oldest old has occurred
worldwide. The aim of this study was to characterize the functional capacity of
the oldest old residents in a long-stay institution in Rio de Janeiro, Brazil.
[Subjects and Methods] All participants were evaluated according to the following
metrics: anthropometry, body composition (bioelectrical impedance), handgrip
strength, balance (Berg scale and stabilometry), ankle mobility
(electrogoniometry), physical capacity (six-minute walk test), quality of life
(WHOQOL-OLD), and dietary habits (questionnaire). [Results] Twenty elderly
subjects with a mean age of 85.75 +/- 5.22 years and a mean fat percentage of
39.02 +/- 5.49% participated in the study. The group at risk of falls (n = 8) had
a lower handgrip strength and walked a shorter distance over the course of six
minutes compared with the group not at risk of falls. The obese group (n = 15)
had higher values for stabilometric variables than the nonobese group. There was
a positive and significant correlation between ankle joint mobility and physical
capacity (r = 0.47). [Conclusion] High values for obesity and low values for
handgrip strength and physical capacity were associated with worse body balance.
Low values for ankle mobility were also associated with worse physical capacity
in this population.
PMID- 25140107
TI - Clinical Study of Respiratory Function and Difference in Pneumonia History
between Alzheimer's Disease and Vascular Dementia Groups.
AB - [Purpose] This study compared respiratory function and differences in pneumonia
history between Alzheimer's disease and vascular dementia groups. [Subjects]
Fifty-eight inpatients in the dementia treatment ward in a psychiatric facility
were enrolled. [Methods] Patients underwent respiratory function testing twice
using an 80-cm party horn. The Mini-Mental State Examination was also performed
and motor functions were evaluated. Patient characteristics were obtained from
medical records. [Results] Significant differences were noted between Alzheimer's
disease and vascular dementia groups in the ability to blow the party horn to
full length, pneumonia history, and presence of impaired mobility. [Conclusion]
Party horn evaluation may be useful for determining the risk of pneumonia in
patients with dementia.
PMID- 25140109
TI - The psychometric properties of the clock drawing test in South Korea.
AB - [Purpose] The aims of the present study were to analyze the validity and
reliability of the Clock Drawing Test (CDT) as a screening tool for cognitive
impairments in both stroke patients and older adults in South Korea. [Subjects
and Methods] Forty-three stroke patients and 42 elderly residents living in urban
communities were recruited. They were divided into three groups according to K
MMSE scores. Kruskal-Wallis one-way ANOVA was used for construct validity,
Friedman two-way ANOVA for discriminative validity, and Spearman's rank order
correlation coefficient for inter-rater reliability. [Results] Regardless of
groups, construct and discriminative validity tests showed statistically
significant results, and Spearman's rho was over 0.56. [Discussion] CDT
demonstrated acceptable validity and reliability. CDT using the productive
methods and Freedman's scoring systems may be suitable for cognitive decrease in
stroke patients and the elderly.
PMID- 25140108
TI - Brain Activity Associated with the Illusion of Motion Evoked by Different
Vibration Stimulation Devices: An fNIRS Study.
AB - [Purpose] A number of different stimulation devices are used in basic and
clinical research studies, and their frequencies of use vary. However, whether or
not they are equally effective has not been investigated. The purpose of the
present study was to investigate neural activity in the brain during the illusion
of motion evoked by stimulating the tendons of the wrist extensor muscles using
various vibration devices. [Subjects] Twelve right-handed university students
with no history of nervous system disorder or orthopedic disease participated in
the study. [Methods] The wrist extensor tendon was stimulated using 3 different
devices: 1) a vibration stimulation device (SL-0105 LP; Asahi Seisakusho Co.,
Ltd., Saitama, Japan), frequency 80 Hz; 2) a handy massager (YCM-20; Yamazen
Corporation, Osaka, Japan), frequency 70 Hz; and 3) a handy massager (Thrive MD
01; Thrive Co., Ltd., Osaka, Japan), frequency 91.7 Hz. Brain activity was
recorded during stimulation by using functional near-infrared spectroscopy.
[Results] Increased neural activity was observed in both the premotor cortices
and the parietal region in both hemispheres in all 3 cases. The level and
localization of neural activity was comparable for all 3 stimulation devices
used. [Conclusion] This suggests that subjects experience the illusion of motion
while the tendon is being stimulated using any vibration device.
PMID- 25140110
TI - Evaluation of Cranio-cervical Posture in Children with Bruxism Before and After
Bite Plate Therapy: A Pilot Project.
AB - [Purpose] The aim of the present study was to evaluate the effect of a biteplate
on the cranio-cervical posture of children with bruxism. [Subjects and Methods]
Twelve male and female children aged six to 10 years with a diagnosis of bruxism
participated in this study. The children used a biteplate during sleep for 30
days and were submitted to three postural evaluations: initial, immediately
following placement of the biteplate, and at the end of treatment. Posture
analysis was performed with the aid of the Alcimagem((r)) 2.1 program. Data
analysis (IBM SPSS Statistics 2.0) involved descriptive statistics and the
Student's t-test. [Results] A statistically significant difference was found
between the initial cranio-cervical angle and the angle immediately following
placement of the biteplate. However, no statistically significant difference was
found between the initial angle and the angle after one month of biteplate usage.
[Conclusion] No significant change in the cranio-cervical posture of the children
was found one month of biteplate usage. However, a reduction occurred in the
cranio-cervical angle when the biteplate was in position.
PMID- 25140111
TI - Body responses to sound stimulation: a crossover study.
AB - [Purpose] Auditory stimulation is used for the functional assessment of the
saccule and saccule-derived vestibule-cervical reflex in clinical environments.
The present study aimed to clarify the influences of sound stimulation as a type
of auditory stimulation on the body. [Subjects] The subjects were nine healthy
youths (2 males and 7 females). [Methods] FFD, FRT, the muscle hardness of
hamstrings, and RT were measured after the sound stimulation of 1,000 Hz and
70dB. [Results] RT was markedly shortened, and the FFD significantly increased
with sound stimulation. [Conclusion] Sound stimulation improved the RT and
flexibility, possibly resulting in an effective approach in physical therapy.
PMID- 25140112
TI - Effects of tai chi for patients with knee osteoarthritis: a systematic review.
AB - [Purpose] The aim of the present study was to seek evidence for the effectiveness
of Tai Chi for patients with knee osteoarthritis (KOA). [Subjects and Methods]
Systematic searches were conducted of the China Journals Full-text Database,
Pubmed, Medline, Science Direct-Online Journals and CINAHL for studies published
between 2000 and 2012. Studies were evaluated based on following inclusion
criteria: 1) design: randomized control, clinical trial; 2) subjects: patients
with a knee osteoarthritis diagnosis; 3) intervention: exercise involving Tai
Chi; 4) studies published in English or Chinese. [Results] Six randomized control
studies involving Tai Chi and knee osteoarthritis were found. [Conclusion] Tai
Chi was an effective way of relieving pain and improving physical function.
Further randomized controlled trials with large sample sizes and long training
period are needed to compare groups who perform Tai Chi training with other
groups who undergo other forms of physical exercise in order to confirm the
efficacy of Tai Chi.
PMID- 25140113
TI - Cross-generational vowel change in American English.
AB - This study examines cross-generational changes in the vowel systems in central
Ohio, southeastern Wisconsin and western North Carolina. Speech samples from 239
speakers, males and females, were divided into three age groups: grandparents (66
91 years old), parents (35-51) and children (8-12). Acoustic analysis of vowel
dynamics (i.e., formant movement) was undertaken to explore variation in the
amount of spectral change for each vowel. A robust set of cross-generational
changes in /i, epsilon, ae, alpha/ was found within each dialect-specific vowel
system, involving both their positions and dynamics. With each successive
generation, /i, epsilon, ae/ become increasingly monophthongized and /alpha/ is
diphthongized in children. These changes correspond to a general anticlockwise
parallel rotation of vowels (with some exceptions in /i/ and /epsilon/). Given
the widespread occurrence of these parallel chain-like changes, we term this
development the "North American Shift" which conforms to the general principles
of chain shifting formulated by Labov (1994) and others.
PMID- 25140114
TI - Rotenone remarkably attenuates oxidative stress, inflammation, and fibrosis in
chronic obstructive uropathy.
AB - Mitochondrial abnormality has been shown in many kidney disease models. However,
its role in the pathogenesis of chronic kidney diseases (CKDs) is still
uncertain. In present study, a mitochondrial complex I inhibitor rotenone was
applied to the mice subjected to unilateral ureteral obstruction (UUO). Following
7-days rotenone treatment, a remarkable attenuation of tubular injury was
detected by PAS staining. In line with the improvement of kidney morphology,
rotenone remarkably blunted fibrotic response as shown by downregulation of
fibronectin (FN), plasminogen activator inhibitor-1 (PAI-1), collagen I, collagen
III, and alpha-SMA, paralleled with a substantial decrease of TGF-beta 1.
Meanwhile, the oxidative stress markers thiobarbituric acid-reactive substances
(TBARS) and heme oxygenase 1 (HO-1) and inflammatory markers TNF-alpha, IL-1beta,
and ICAM-1 were markedly decreased. More importantly, the reduction of
mitochondrial DNA copy number and mitochondrial NADH dehydrogenase subunit 1
(mtND1) expression in obstructed kidneys was moderately but significantly
restored by rotenone, suggesting an amelioration of mitochondrial injury.
Collectively, mitochondrial complex I inhibitor rotenone protected kidneys
against obstructive injury possibly via inhibition of mitochondrial oxidative
stress, inflammation, and fibrosis, suggesting an important role of mitochondrial
dysfunction in the pathogenesis of obstructive kidney disease.
PMID- 25140115
TI - Tumor necrosis factor is a therapeutic target for immunological unbalance and
cardiac abnormalities in chronic experimental Chagas' heart disease.
AB - BACKGROUND: Chagas disease (CD) is characterized by parasite persistence and
immunological unbalance favoring systemic inflammatory profile. Chronic chagasic
cardiomyopathy, the main manifestation of CD, occurs in a TNF-enriched milieu and
frequently progresses to heart failure. AIM OF THE STUDY: To challenge the
hypothesis that TNF plays a key role in Trypanosoma cruzi-induced immune
deregulation and cardiac abnormalities, we tested the effect of the anti-TNF
antibody Infliximab in chronically T. cruzi-infected C57BL/6 mice, a model with
immunological, electrical, and histopathological abnormalities resembling Chagas'
heart disease. RESULTS: Infliximab therapy did not reactivate parasite but
reshaped the immune response as reduced TNF mRNA expression in the cardiac tissue
and plasma TNF and IFNgamma levels; diminished the frequency of IL-17A(+) but
increased IL-10(+) CD4(+) T-cells; reduced TNF(+) but augmented IL-10(+) Ly6C(+)
and F4/80(+) cells. Further, anti-TNF therapy decreased cytotoxic activity but
preserved IFNgamma-producing VNHRFTLV-specific CD8(+) T-cells in spleen and
reduced the number of perforin(+) cells infiltrating the myocardium. Importantly,
Infliximab reduced the frequency of mice afflicted by arrhythmias and second
degree atrioventricular blocks and decreased fibronectin deposition in the
cardiac tissue. CONCLUSIONS: Our data support that TNF is a crucial player in the
pathogenesis of Chagas' heart disease fueling immunological unbalance which
contributes to cardiac abnormalities.
PMID- 25140116
TI - Cell death-associated molecular-pattern molecules: inflammatory signaling and
control.
AB - Apoptosis, necroptosis, and pyroptosis are different cellular death programs
characterized in organs and tissues as consequence of microbes infection, cell
stress, injury, and chemotherapeutics exposure. Dying and death cells release a
variety of self-proteins and bioactive chemicals originated from cytosol,
nucleus, endoplasmic reticulum, and mitochondria. These endogenous factors are
named cell death-associated molecular-pattern (CDAMP), damage-associated
molecular-pattern (DAMP) molecules, and alarmins. Some of them cooperate or act
as important initial or delayed inflammatory mediators upon binding to diverse
membrane and cytosolic receptors coupled to signaling pathways for the activation
of the inflammasome platforms and NF-kappaB multiprotein complexes. Current
studies show that the nonprotein thiols and thiol-regulating enzymes as well as
highly diffusible prooxidant reactive oxygen and nitrogen species released
together in extracellular inflammatory milieu play essential role in controlling
pro- and anti-inflammatory activities of CDAMP/DAMP and alarmins. Here, we
provide an overview of these emerging concepts and mechanisms of triggering and
maintenance of tissue inflammation under massive death of cells.
PMID- 25140117
TI - Peritoneal air exposure elicits an intestinal inflammation resulting in
postoperative ileus.
AB - BACKGROUND: The pathogenesis of postoperative ileus (POI) is complex. The present
study was designed to investigate the effects of peritoneal air exposure on the
POI intestinal inflammation and the underlying mechanism. METHODS: Sprague-Dawley
rats were randomized into five groups (6/group): the control group, the sham
group, and three exposure groups with peritoneal air exposure for 1, 2, or 3 h.
At 24 h after surgery, we analyzed the gastrointestinal transit, the serum levels
of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-10,
the myeloperoxidase activity, and the levels of TNF-alpha, IL-1beta, IL-6, and IL
10 in the ileum and colon. The oxidant and antioxidant levels in the ileum and
colon were analyzed by measuring malondialdehyde (MDA), superoxide dismutase
(SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC).
RESULTS: Peritoneal air exposure caused an air-exposure-time-dependent decrease
in the gastrointestinal transit. The length of peritoneal air exposure is
correlated with the severity of both systemic and intestinal inflammations and
the increases in the levels of MDA, SOD, GSH-Px, and T-AOC. CONCLUSIONS: The
length of peritoneal air exposure is proportional to the degree of intestinal
paralysis and the severity of intestinal inflammation, which is linked to the
oxidative stress response.
PMID- 25140118
TI - Combined first-trimester screening in northern Finland: experiences of the first
ten years.
AB - OBJECTIVE: To evaluate the efficacy of first trimester combined screening for
Down's syndrome in Northern Finland during the first 10 years of practice.
METHODS: During 1 January 2002 to 31 December 2011, 47,896 women participated
voluntarily in combined screening during first trimester. The risk cutoff was
1:250. The study period was divided into two time periods; 2002-2006 and 2007
2011. RESULTS: During the first half of the study period, the detection rate (DR)
was 77.3% with a 4.9% false-positive rate (FPR). During the latter half, the DR
was 77.1% with a 2.8% FPR. CONCLUSIONS: An important issue is the number of
invasive procedures needed to detect one case of Down's syndrome. The screening
performance improved markedly in the latter five years period since the FPR
lowered from 4.9% to 2.8% and the number of invasive procedures needed to detect
one case of Down's syndrome lowered from 15 to 11.
PMID- 25140120
TI - Consecutively preparing d-xylose, organosolv lignin, and amorphous ultrafine
silica from rice husk.
AB - Rice husk is an abundant agricultural by-product reaching the output of 80
million tons annually in the world. The most common treatment method of rice husk
is burning or burying, which caused serious air pollution and resource waste. In
order to solve this problem, a new method is proposed to comprehensively utilize
the rice husk in this paper. Firstly, the D-xylose was prepared from the
semicellulose via dilute acid hydrolysis. Secondly, the lignin was separated via
organic solvent pulping from the residue. Finally, the amorphous ultrafine silica
was prepared via pyrolysis of the residue produced in the second process. In this
way, the three main contents of rice husk (semicellulose, lignin, and silica) are
consecutively converted to three fine chemicals, without solid waste produced.
The yields of D-xylose and organosolv lignin reach 58.2% and 58.5%, respectively.
The purity and specific surface of amorphous ultrafine silica reach 99.92% and
225.20 m(2)/g.
PMID- 25140119
TI - A qualitative investigation of the roles and perspectives of older patients with
advanced cancer and their family caregivers in managing pain in the home.
AB - BACKGROUND: Pain in advanced cancer is complex and multifaceted. In older
patients comorbidities and age-related functional decline add to the difficulties
in managing cancer pain. The current emphasis on care in the community, and
preference by patients with life-limiting disease to receive care in the home,
has meant that patients and their family caregivers have become increasingly
responsible for the day-to-day management of cancer pain. An appreciation of
patients' and caregivers' roles and perspectives managing pain is, therefore,
fundamental to addressing cancer pain in this setting. Consequently, we sought to
explore and describe their perspectives and roles. METHODS: A qualitative
descriptive approach was used. Semi-structured interviews were conducted with a
purposeful sample of patient- family caregiver dyads. Participants included 18
patients aged 65 years and over, with advanced cancer, receiving palliative care
at home, and 15 family caregivers. The interview data were analysed using
thematic analyses. Strategies were used to establish rigour. RESULTS: Two main
themes were identified. The first theme, "Communicating the pain", represented
pain assessment and incorporated four subthemes in which participants described:
their roles in pain assessment, the identification and expression of pain, and
the communication of pain between patients and caregivers. The second theme,
"Finding a solution", comprised of four subthemes that reflected participants'
roles and approaches in controlling pain; as well as their beliefs about cancer
pain control, experience with side effects, and perspectives on the goals of
treatment. CONCLUSIONS: The findings support other studies in identifying
knowledge and attitudinal barriers to pain control; while adding to the
literature by highlighting practical and relational barriers faced by older
patients and their family caregivers. Health care professionals can do much to
address the barriers identified by: correcting misconceptions regarding cancer
pain, facilitating the communication of pain within dyads, and ensuring that
patients and family caregivers have the knowledge, skills, and ability to assess
and implement pain treatment strategies. This support needs to be individually
tailored to meet the ongoing needs of both members of the dyad so that the shared
goals of pain management are accomplished.
PMID- 25140121
TI - Synthesis and Spectroscopic Characterization of Some New Axially Ligated
Indium(III) Macrocyclic Complexes and Their Biological Activities.
AB - The synthesis and spectroscopic characterization of new axially ligated
indium(III) porphyrin complexes were reported. Chloroindium(III) porphyrin (TPPIn
Cl) was obtained in good yield by treating the corresponding free base with
indium trichloride. The action of the different phenols on chloroderivatives
(TPPIn-Cl) led to the corresponding phenolato complexes (TPPIn-X). These
derivatives were characterized on the basis of mass spectrometry, (1)H-NMR, IR,
and UV-visible data. The separation and isolation of these derivatives have been
achieved through chromatography. The spectral properties of free base porphyrin
and its corresponding metallated and axially ligated indium(III) porphyrin
compounds were compared with each other. A detailed analysis of UV-Vis, (1)H-NMR,
and IR suggested the transformation from free base porphyrin to indium(III)
porphyrin. Besides, (13)C-NMR and fluorescence spectra were also reported and
interpreted. The stability of these derivatives has also been studied through
thermogravimetry. The complexes were also screened for anticancerous activities.
Among all the complexes, 4-MePhO-InTPP shows highest anticancerous activity. The
title complexe, TPPIn-X (where X = different phenolates), represents a five
coordinate indium(III) porphyrin complex in a square-pyramidal geometry with the
phenolate anion as the axial ligand.
PMID- 25140122
TI - Determination of the total mass of antioxidant substances and antioxidant
capacity per unit mass in serum using redox titration.
AB - Objective. Total antioxidant capacity in serum is determined by the total mass of
antioxidant substances and the antioxidant capacity per unit mass (average
activity). The purpose of this study was to develop a method to determine the
mass of antioxidant substances and average activity in human serum. Methods.
Specimens of serum were collected from 100 subjects each from two different age
groups: over 75 years old and 20-40 years old. The test serum was diluted into a
series of concentrations, following which standard oxidation agents (KMnO4 for
potassium permanganate method and I2 for iodimetry) were added to each
concentration of serum, and the absorbance of the mixture (optical density, OD)
was measured. The OD value and logarithm of dilution factor (lgT) at the end of
the titration were obtained, from which the lgT could be considered as mass of
antioxidant substances (M). Total antioxidant capacity (Ta) was calculated with
the equation Ta = 100/(OD1 + 2 * OD2 + 2 * OD3 + 2 * OD4 + OD5), and average
activity (A) was calculated as A = Ta/M. Results. The potassium permanganate
method generated similar results to the iodimetric method. Compared with the
younger group, total antioxidant capacity in the over-75-year age group was found
to be significantly reduced, along with a decrease in the mass of antioxidant
substances and average activity levels in human serum. Conclusions. The approach
described in this paper is suitable for determining the average activity and mass
of antioxidant substances in human serum.
PMID- 25140123
TI - Socioeconomic differences in selected dietary habits among Norwegian 13-14 year
olds: a cross-sectional study.
AB - BACKGROUND: Social inequalities in health are a major and even growing problem in
all European countries. OBJECTIVE: The aim of the present study was to describe
1) differences in dietary habits among Norwegian adolescents by gender and
socioeconomic status; 2) differences in self-reported knowledge of dietary
guidelines among their parents according to socioeconomic status. DESIGN: In
2012, a cross-sectional study where students filled in a web-based food frequency
questionnaire at school was conducted in nine lower secondary schools in Vest
Agder County, Norway. Socioeconomic status (SES) and knowledge of dietary
guidelines were obtained from the parents using a web-based questionnaire. In
total, 517 ninth-grade students (mean age 13.9) out of 742 invited students
participated in the study, giving a participation rate of 69.7%. The total number
of dyads with information on both parents and students was 308 (41.5%). RESULTS:
The findings indicate that there is a tendency for girls to have a healthier diet
than boys, with greater intake of fruits and vegetables (girls intake in median
3.5 units per day and boys 2.9 units per day), and lower intake of soft drinks
(girls 0.25 l in median versus boys 0.5 l per week). Students from families with
higher SES reported a significant higher intake of vegetables and fish, and lower
intake of soft drinks and fast food than those from lower SES. Parents with
higher SES reported a significantly better knowledge of dietary guidelines
compared to those with lower SES. CONCLUSIONS: Differences in dietary habits were
found between groups of students by gender and SES. Differences were also found
in parents' self-reported knowledge of dietary guidelines. This social patterning
should be recognized in public health interventions.
PMID- 25140124
TI - A comparative study of drift diffusion and linear ballistic accumulator models in
a reward maximization perceptual choice task.
AB - We present new findings that distinguish drift diffusion models (DDMs) from the
linear ballistic accumulator (LBA) model as descriptions of human behavior in a
two-alternative forced-choice reward maximization (Rmax) task. Previous
comparisons have not considered Rmax tasks, and differences identified between
the models' predictions have centered on practice effects. Unlike the parameter
free optimal performance curves of the pure DDM, the extended DDM and LBA predict
families of curves depending on their additional parameters, and those of the LBA
show significant differences from the DDMs, especially for poorly discriminable
stimuli that incur high error rates. Moreover, fits to behavior reveal that the
LBA and DDM provide different interpretations of behavior as stimulus
discriminability increases. Trends for threshold setting (caution) in the DDMs
are consistent between fits, while in the corresponding LBA fits, thresholds
interact with distributions of starting points in a complex manner that depends
upon parameter constraints. Our results suggest that reinterpretation of LBA
parameters may be necessary in modeling the Rmax paradigm.
PMID- 25140126
TI - Sex differences in self-regulation: an evolutionary perspective.
AB - Bjorklund and Kipp (1996) provide an evolutionary framework predicting that there
is a female advantage in inhibition and self-regulation due to differing
selection pressures placed on males and females. The majority of the present
review will summarize sex differences in self-regulation at the behavioral level.
The neural and hormonal underpinnings of this potential sexual dimorphism will
also be investigated and the results of the experiments summarized will be
related to the hypothesis advanced by Bjorklund and Kipp (1996). Paradoxically,
sex differences in self-regulation are more consistently reported in children
prior to the onset of puberty. In adult cohorts, the results of studies examining
sex differences in self-regulation are mixed. A few recent experiments suggesting
that females are less impulsive than males only during fertile stages of the
menstrual cycle will be reviewed. A brief discussion of an evolutionary framework
proposing that it is adaptive for females to employ a self-regulatory behavioral
strategy when fertile will follow.
PMID- 25140125
TI - Sexual attractiveness of male chemicals and vocalizations in mice.
AB - Male-female interaction is important for finding a suitable mating partner and
for ensuring reproductive success. Male sexual signals such as pheromones
transmit information and social and sexual status to females, and exert powerful
effects on the mate preference and reproductive biology of females. Likewise,
male vocalizations are attractive to females and enhance reproductive function in
many animals. Interestingly, females' preference for male pheromones and
vocalizations is associated with their genetic background, to avoid inbreeding.
Moreover, based on acoustic cues, olfactory signals have significant effects on
mate choice in mice, suggesting mate choice involves multisensory integration. In
this review, we synopsize the effects of both olfactory and auditory cues on
female behavior and neuroendocrine functions. We also discuss how these male
signals are integrated and processed in the brain to regulate behavior and
reproductive function.
PMID- 25140128
TI - Haptoglobin increases with age in rat hippocampus and modulates Apolipoprotein E
mediated cholesterol trafficking in neuroblastoma cell lines.
AB - Alteration in cholesterol metabolism has been implicated in the pathogenesis of
several neurodegenerative disorders. Apolipoprotein E (ApoE) is the major
component of brain lipoproteins supporting cholesterol transport. We previously
reported that the acute-phase protein Haptoglobin (Hpt) binds ApoE, and
influences its function in blood cholesterol homeostasis. Major aim of this study
was to investigate whether Hpt influences the mechanisms by which cholesterol is
shuttled from astrocytes to neurons. In detail it was studied Hpt effect on ApoE
dependent cholesterol efflux from astrocytes and ApoE-mediated cholesterol
incorporation in neurons. We report here that Hpt impairs ApoE-mediated
cholesterol uptake in human neuroblastoma cell line SH-SY5Y, and limits the
toxicity of a massive concentration of cholesterol for these cells, while it does
not affect cholesterol efflux from the human glioblastoma-astrocytoma cell line U
87 MG. As aging is the most important non-genetic risk factor for various
neurodegenerative disorders, and our results suggest that Hpt modulates ApoE
functions, we evaluated the Hpt and ApoE expression profiles in cerebral cortex
and hippocampus of adolescent (2 months), adult (5 and 8 months), and middle-aged
(16 months) rats. Hpt mRNA level was higher in hippocampus of 8 and 16 month-old
than in 2-month old rats (p < 0.05), and Hpt concentration increased with the age
from adolescence to middle-age (p < 0.001). ApoE concentration, in hippocampus,
was higher (p < 0.001) in 5 month-old rats compared to 2 month but did not
further change with aging. No age-related changes of Hpt (protein and mRNA) were
found in the cortex. Our results suggest that aging is associated with changes,
particularly in the hippocampus, in the Hpt/ApoE ratio. Age-related changes in
the concentration of Hpt were also found in human cerebrospinal fluids. The age
related changes might affect neuronal function and survival in brain, and have
important implications in brain pathophysiology.
PMID- 25140129
TI - Changes in complex spike activity during classical conditioning.
AB - The cerebellar cortex is necessary for adaptively timed conditioned responses
(CRs) in eyeblink conditioning. During conditioning, Purkinje cells acquire pause
responses or "Purkinje cell CRs" to the conditioned stimuli (CS), resulting in
disinhibition of the cerebellar nuclei (CN), allowing them to activate motor
nuclei that control eyeblinks. This disinhibition also causes inhibition of the
inferior olive (IO), via the nucleo-olivary pathway (N-O). Activation of the IO,
which relays the unconditional stimulus (US) to the cortex, elicits
characteristic complex spikes in Purkinje cells. Although Purkinje cell activity,
as well as stimulation of the CN, is known to influence IO activity, much remains
to be learned about the way that learned changes in simple spike firing affects
the IO. In the present study, we analyzed changes in simple and complex spike
firing, in extracellular Purkinje cell records, from the C3 zone, in decerebrate
ferrets undergoing training in a conditioning paradigm. In agreement with the N-O
feedback hypothesis, acquisition resulted in a gradual decrease in complex spike
activity during the conditioned stimulus, with a delay that is consistent with
the long N-O latency. Also supporting the feedback hypothesis, training with a
short interstimulus interval (ISI), which does not lead to acquisition of a
Purkinje cell CR, did not cause a suppression of complex spike activity. In
contrast, observations that extinction did not lead to a recovery in complex
spike activity and the irregular patterns of simple and complex spike activity
after the conditioned stimulus are less conclusive.
PMID- 25140131
TI - Measuring F-actin properties in dendritic spines.
AB - During the last decade, numerous studies have demonstrated that the actin
cytoskeleton plays a pivotal role in the control of dendritic spine shape.
Synaptic stimulation rapidly changes the actin dynamics and many actin regulators
have been shown to play roles in neuron functionality. Accordingly, defects in
the regulation of the actin cytoskeleton in neurons have been implicated in
memory disorders. Due to the small size of spines, it is difficult to detect
changes in the actin structures in dendritic spines by conventional light
microscopy imaging. Instead, to know how tightly actin filaments are bundled
together, and how fast the filaments turnover, we need to use advanced microscopy
techniques, such as fluorescence recovery after photobleaching (FRAP),
photoactivatable green fluorescent protein (PAGFP) fluorescence decay and
fluorescence anisotropy. Fluorescence anisotropy, which measures the Forster
resonance energy transfer (FRET) between two GFP fluorophores, has been proposed
as a method to measure the level of actin polymerization. Here, we propose a
novel idea that fluorescence anisotropy could be more suitable to study the level
of actin filament bundling instead of actin polymerization. We validate the
method in U2OS cell line where the actin structures can be clearly distinguished
and apply to analyze how actin filament organization in dendritic spines changes
during neuronal maturation. In addition to fluorescence anisotropy validation, we
take a critical look at the properties and limitations of FRAP and PAGFP
fluorescence decay methods and offer our proposals for the analysis methods for
these approaches. These three methods complement each other, each providing
additional information about actin dynamics and organization in dendritic spines.
PMID- 25140132
TI - Retino-hypothalamic regulation of light-induced murine sleep.
AB - The temporal organization of sleep is regulated by an interaction between the
circadian clock and homeostatic processes. Light indirectly modulates sleep
through its ability to phase shift and entrain the circadian clock. Light can
also exert a direct, circadian-independent effect on sleep. For example, acute
exposure to light promotes sleep in nocturnal animals and wake in diurnal
animals. The mechanisms whereby light directly influences sleep and arousal are
not well understood. In this review, we discuss the direct effect of light on
sleep at the level of the retina and hypothalamus in rodents. We review murine
data from recent publications showing the roles of rod-, cone- and melanopsin
based photoreception on the initiation and maintenance of light-induced sleep. We
also present hypotheses about hypothalamic mechanisms that have been advanced to
explain the acute control of sleep by light. Specifically, we review recent
studies assessing the roles of the ventrolateral preoptic area (VLPO) and the
suprachiasmatic nucleus (SCN). We also discuss how light might differentially
promote sleep and arousal in nocturnal and diurnal animals respectively. Lastly,
we suggest new avenues for research on this topic which is still in its early
stages.
PMID- 25140133
TI - Speech sound discrimination training improves auditory cortex responses in a rat
model of autism.
AB - Children with autism often have language impairments and degraded cortical
responses to speech. Extensive behavioral interventions can improve language
outcomes and cortical responses. Prenatal exposure to the antiepileptic drug
valproic acid (VPA) increases the risk for autism and language impairment.
Prenatal exposure to VPA also causes weaker and delayed auditory cortex responses
in rats. In this study, we document speech sound discrimination ability in VPA
exposed rats and document the effect of extensive speech training on auditory
cortex responses. VPA exposed rats were significantly impaired at consonant, but
not vowel, discrimination. Extensive speech training resulted in both stronger
and faster anterior auditory field (AAF) responses compared to untrained VPA
exposed rats, and restored responses to control levels. This neural response
improvement generalized to non-trained sounds. The rodent VPA model of autism may
be used to improve the understanding of speech processing in autism and
contribute to improving language outcomes.
PMID- 25140130
TI - Dopamine modulation of learning and memory in the prefrontal cortex: insights
from studies in primates, rodents, and birds.
AB - In this review, we provide a brief overview over the current knowledge about the
role of dopamine transmission in the prefrontal cortex during learning and
memory. We discuss work in humans, monkeys, rats, and birds in order to provide a
basis for comparison across species that might help identify crucial features and
constraints of the dopaminergic system in executive function. Computational
models of dopamine function are introduced to provide a framework for such a
comparison. We also provide a brief evolutionary perspective showing that the
dopaminergic system is highly preserved across mammals. Even birds, following a
largely independent evolution of higher cognitive abilities, have evolved a
comparable dopaminergic system. Finally, we discuss the unique advantages and
challenges of using different animal models for advancing our understanding of
dopamine function in the healthy and diseased brain.
PMID- 25140134
TI - Brain-machine interfacing control of whole-body humanoid motion.
AB - We propose to tackle in this paper the problem of controlling whole-body humanoid
robot behavior through non-invasive brain-machine interfacing (BMI), motivated by
the perspective of mapping human motor control strategies to human-like
mechanical avatar. Our solution is based on the adequate reduction of the
controllable dimensionality of a high-DOF humanoid motion in line with the state
of-the-art possibilities of non-invasive BMI technologies, leaving the complement
subspace part of the motion to be planned and executed by an autonomous humanoid
whole-body motion planning and control framework. The results are shown in full
physics-based simulation of a 36-degree-of-freedom humanoid motion controlled by
a user through EEG-extracted brain signals generated with motor imagery task.
PMID- 25140135
TI - Oxytocin increases liking for a country's people and national flag but not for
other cultural symbols or consumer products.
AB - The neuropeptide oxytocin enhances in-group favoritism and ethnocentrism in
males. However, whether such effects also occur in women and extend to national
symbols and companies/consumer products is unclear. In a between-subject, double
blind placebo controlled experiment we have investigated the effect of intranasal
oxytocin on likeability and arousal ratings given by 51 adult Chinese males and
females for pictures depicting people or national symbols/consumer products from
both strong and weak in-groups (China and Taiwan) and corresponding out-groups
(Japan and South Korea). To assess duration of treatment effects subjects were
also re-tested after 1 week. Results showed that although oxytocin selectively
increased the bias for overall liking for Chinese social stimuli and the national
flag, it had no effect on the similar bias toward other Chinese cultural symbols,
companies, and consumer products. This enhanced bias was maintained 1 week after
treatment. No overall oxytocin effects were found for Taiwanese, Japanese, or
South Korean pictures. Our findings show for the first time that oxytocin
increases liking for a nation's society and flag in both men and women, but not
that for other cultural symbols or companies/consumer products.
PMID- 25140136
TI - Tuning and disrupting the brain-modulating the McGurk illusion with electrical
stimulation.
AB - In the so-called McGurk illusion, when the synchronized presentation of the
visual stimulus /ga/ is paired with the auditory stimulus /ba/, people in general
hear it as /da/. Multisensory integration processing underlying this illusion
seems to occur within the Superior Temporal Sulcus (STS). Herein, we present
evidence demonstrating that bilateral cathodal transcranial direct current
stimulation (tDCS) of this area can decrease the McGurk illusion-type responses.
Additionally, we show that the manipulation of this audio-visual integrated
output occurs irrespective of the number of eye-fixations on the mouth of the
speaker. Bilateral anodal tDCS of the Parietal Cortex also modulates the
illusion, but in the opposite manner, inducing more illusion-type responses. This
is the first demonstration of using non-invasive brain stimulation to modulate
multisensory speech perception in an illusory context (i.e., both increasing and
decreasing illusion-type responses to a verbal audio-visual integration task).
These findings provide clear evidence that both the superior temporal and
parietal areas contribute to multisensory integration processing related to
speech perception. Specifically, STS seems fundamental for the temporal
synchronization and integration of auditory and visual inputs. For its part,
posterior parietal cortex (PPC) may adjust the arrival of incoming audio and
visual information to STS thereby enhancing their interaction in this latter
area.
PMID- 25140137
TI - Face processing improvements in prosopagnosia: successes and failures over the
last 50 years.
AB - Clinicians and researchers have widely believed that face processing cannot be
improved in prosopagnosia. Though more than a dozen reported studies have
attempted to enhance face processing in prosopagnosics over the last 50 years,
evidence for effective treatment approaches has only begun to emerge. Here, we
review the current literature on spontaneous recovery in acquired prosopagnosia
(AP), as well as treatment attempts in acquired and developmental prosopagnosia
(DP), differentiating between compensatory and remedial approaches. We find that
for AP, rather than remedial methods, strategic compensatory training such as
verbalizing distinctive facial features has shown to be the most effective
approach (despite limited evidence of generalization). In children with DP,
compensatory training has also shown some effectiveness. In adults with DP, two
recent larger-scale studies, one using remedial training and another
administering oxytocin, have demonstrated group-level improvements and evidence
of generalization. These results suggest that DPs, perhaps because of their more
intact face processing infrastructure, may benefit more from treatments targeting
face processing than APs.
PMID- 25140138
TI - Eluding the illusion? Schizophrenia, dopamine and the McGurk effect.
AB - Perceptions are inherently probabilistic; and can be potentially manipulated to
induce illusory experience by the presentation of ambiguous or improbable
evidence under selective (spatio-temporal) constraints. Accordingly, perception
of the McGurk effect, by which individuals misperceive specific incongruent
visual and auditory vocal cues, rests upon effective probabilistic inference.
Here, we report findings from a behavioral investigation of illusory perception
and related metacognitive evaluation during audiovisual integration, conducted in
individuals with schizophrenia (n = 30) and control subjects (n = 24) matched in
terms of age, sex, handedness and parental occupation. Controls additionally
performed the task after an oral dose of amisulpride (400 mg). Individuals with
schizophrenia were observed to exhibit illusory perception less frequently than
controls, despite non-significant differences in perceptual performance during
control conditions. Furthermore, older individuals with schizophrenia exhibited
reduced rates of illusory perception. Subsequent analysis revealed a robust
inverse relationship between illness chronicity and the illusory perception rate
in this group. Controls demonstrated non-significant modulation of perception by
amisulpride; amisulpride was, however, found to elicit increases in subjective
confidence in perceptual performance. Overall, these findings are consistent with
the idea that impairments in probabilistic inference are exhibited in
schizophrenia and exacerbated by illness chronicity. The latter suggests that
associated processes are a potentially worthwhile target for therapeutic
intervention.
PMID- 25140139
TI - Challenges for identifying the neural mechanisms that support spatial navigation:
the impact of spatial scale.
AB - Spatial navigation is a fascinating behavior that is essential for our everyday
lives. It involves nearly all sensory systems, it requires numerous parallel
computations, and it engages multiple memory systems. One of the key problems in
this field pertains to the question of reference frames: spatial information such
as direction or distance can be coded egocentrically-relative to an observer-or
allocentrically-in a reference frame independent of the observer. While many
studies have associated striatal and parietal circuits with egocentric coding and
entorhinal/hippocampal circuits with allocentric coding, this strict dissociation
is not in line with a growing body of experimental data. In this review, we
discuss some of the problems that can arise when studying the neural mechanisms
that are presumed to support different spatial reference frames. We argue that
the scale of space in which a navigation task takes place plays a crucial role in
determining the processes that are being recruited. This has important
implications, particularly for the inferences that can be made from animal
studies in small scale space about the neural mechanisms supporting human spatial
navigation in large (environmental) spaces. Furthermore, we argue that many of
the commonly used tasks to study spatial navigation and the underlying neuronal
mechanisms involve different types of reference frames, which can complicate the
interpretation of neurophysiological data.
PMID- 25140140
TI - Listening effort and accented speech.
PMID- 25140142
TI - Left occipitotemporal cortex contributes to the discrimination of tool-associated
hand actions: fMRI and TMS evidence.
AB - Functional neuroimaging studies have implicated the left lateral occipitotemporal
cortex (LOTC) in both tool and hand perception but the functional role of this
region is not fully known. Here, by using a task manipulation, we tested whether
tool-/hand-selective LOTC contributes to the discrimination of tool-associated
hand actions. Participants viewed briefly presented pictures of kitchen and
garage tools while they performed one of two tasks: in the action task, they
judged whether the tool is associated with a hand rotation action (e.g.,
screwdriver) or a hand squeeze action (e.g., garlic press), while in the location
task they judged whether the tool is typically found in the kitchen (e.g., garlic
press) or in the garage (e.g., screwdriver). Both tasks were performed on the
same stimulus set and were matched for difficulty. Contrasting fMRI responses
between these tasks showed stronger activity during the action task than the
location task in both tool- and hand-selective LOTC regions, which closely
overlapped. No differences were found in nearby object- and motion-selective
control regions. Importantly, these findings were confirmed by a TMS study, which
showed that effective TMS over the tool-/hand-selective LOTC region significantly
slowed responses for tool action discriminations relative to tool location
discriminations, with no such difference during sham TMS. We conclude that left
LOTC contributes to the discrimination of tool-associated hand actions.
PMID- 25140141
TI - Cues, context, and long-term memory: the role of the retrosplenial cortex in
spatial cognition.
AB - Spatial navigation requires memory representations of landmarks and other
navigation cues. The retrosplenial cortex (RSC) is anatomically positioned
between limbic areas important for memory formation, such as the hippocampus
(HPC) and the anterior thalamus, and cortical regions along the dorsal stream
known to contribute importantly to long-term spatial representation, such as the
posterior parietal cortex. Damage to the RSC severely impairs allocentric
representations of the environment, including the ability to derive navigational
information from landmarks. The specific deficits seen in tests of human and
rodent navigation suggest that the RSC supports allocentric representation by
processing the stable features of the environment and the spatial relationships
among them. In addition to spatial cognition, the RSC plays a key role in
contextual and episodic memory. The RSC also contributes importantly to the
acquisition and consolidation of long-term spatial and contextual memory through
its interactions with the HPC. Within this framework, the RSC plays a dual role
as part of the feedforward network providing sensory and mnemonic input to the
HPC and as a target of the hippocampal-dependent systems consolidation of long
term memory.
PMID- 25140144
TI - The joint Simon effect depends on perceived agency, but not intentionality, of
the alternative action.
AB - A co-actor's intentionality has been suggested to be a key modulating factor for
joint action effects like the joint Simon effect (JSE). However, in previous
studies intentionality has often been confounded with agency defined as
perceiving the initiator of an action as being the causal source of the action.
The aim of the present study was to disentangle the role of agency and
intentionality as modulating factors of the JSE. In Experiment 1, participants
performed a joint go/nogo Simon task next to a co-actor who either intentionally
controlled a response button with own finger movements (agency+/intentionality+)
or who passively placed the hand on a response button that moved up and down on
its own as triggered by computer signals (agency-/intentionality-). In Experiment
2, we included a condition in which participants believed that the co-actor
intentionally controlled the response button with a Brain-Computer Interface
(BCI) while placing the response finger clearly besides the response button, so
that the causal relationship between agent and action effect was perceptually
disrupted (agency-/intentionality+). As a control condition, the response button
was computer controlled while the co-actor placed the response finger besides the
response button (agency-/intentionality-). Experiment 1 showed that the JSE is
present with an intentional co-actor and causality between co-actor and action
effect, but absent with an unintentional co-actor and a lack of causality between
co-actor and action effect. Experiment 2 showed that the JSE is absent with an
intentional co-actor, but no causality between co-actor and action effect. Our
findings indicate an important role of the co-actor's agency for the JSE. They
also suggest that the attribution of agency has a strong perceptual basis.
PMID- 25140143
TI - Effective connectivity among the working memory regions during preparation for
and during performance of the n-back task.
AB - Recent neuroimaging studies have shown that working memory (WM) task difficulty
can be decoded from patterns of brain activation in the WM network during
preparation to perform those tasks. The inter-regional connectivity among the WM
regions during task preparation has not yet been investigated. We examined this
question using the graph modeling methods IMaGES and LOFS, applied to the
previously published fMRI data of Manelis and Reder (2013). In that study,
subjects performed 1-, 2-, and 3-back tasks. Each block of n-back was preceded by
a preparation period and followed by a rest period. The analyses of task-related
brain activity identified a network of 18 regions that increased in activation
from 1- to 3-back (Increase network) and a network of 17 regions that decreased
in activation from 1- to 3-back (Decrease network). The graph analyses revealed
two types of connectivity sub-networks within the Increase and Decrease networks:
"default" and "preparation-related." The "default" connectivity was present not
only during task performance, but also during task preparation and during rest.
We propose that this sub-network may serve as a core system that allows one to
quickly activate cognitive, perceptual and motor systems in response to the
relevant stimuli. The "preparation-related" connectivity was present during task
preparation and task performance, but not at rest, and depended on the n-back
condition. The role of this sub-network may be to pre-activate a connectivity
"road map" in order to establish a top-down and bottom-up regulation of attention
prior to performance on WM tasks.
PMID- 25140145
TI - The hippocampus is not a geometric module: processing environment geometry during
reorientation.
AB - The hippocampus has long been known to play a role in allocentric spatial coding,
but its specific involvement in reorientation, or the recalibration of a
disrupted egocentric spatial representation using allocentric spatial
information, has received less attention. Initially, the cognitive literature on
reorientation focused on a "geometric module" sensitive to the shape formed by
extended surfaces in the environment, and the neuroscience literature followed
with proposals that particular MTL regions might be the seat of such a module.
However, with behavioral evidence mounting that a modular cognitive architecture
is unlikely, recent work has begun to directly address the issue of the neural
underpinnings of reorientation. In this review, we describe the reorientation
paradigm, initial proposals for the role of the MTL when people reorient, our
recent work on the neural bases of reorientation, and finally, how this new
information regarding neural mechanism helps to re-interpret and clarify the
original behavioral reorientation data.
PMID- 25140146
TI - Transcranial stimulation of the developing brain: a plea for extreme caution.
PMID- 25140148
TI - Changes in scalp potentials and spatial smoothing effects of inclusion of dura
layer in human head models for EEG simulations.
AB - The dura layer which covers the brain is less conductive than the CSF
(cerebrospinal fluid) and also more conductive than the skull bone. This could
significantly influence the flow of volume currents from cortex to the scalp
surface which will also change the magnitude and spatial profiles of scalp
potentials. This was examined with a 3-D finite element method (FEM) model of an
adult subject constructed from 192 segmented axial magnetic resonance (MR) slices
with 256*256 pixel resolution. The voxel resolution was 1*1*1 mm. The model
included the dura layer. In addition, other major tissues were also identified.
The electrical conductivities of various tissues were obtained from the
literature. The conductivities of dura and CSF were 0.001 S/m and 0.06 S/m,
respectively. The electrical activity of the cortex was represented by 144,000
distributed dipolar sources with orientations normal to the local cortical
surface. The dipolar intensity was in the range of 0.0-0.4 mA meter with a
uniform random distribution. Scalp potentials were simulated for two head models
with an adaptive finite element solver. One model had the dura layer and in the
other model, dura layer was replaced with the CSF. Spatial contour plots of
potentials on the cortical surface, dural surface and the scalp surface were
made. With the inclusion of the dura layer, scalp potentials decrease by about
20%. The contours of gyri and sulci structures were visible in the spatial
profiles of the cortical potentials which were smoothed out on the dural surface
and were not visible on the scalp surface. These results suggest that dura layer
should be included for an accurate modeling of scalp and cortical potentials.
PMID- 25140149
TI - Genetic variation modifies risk for neurodegeneration based on biomarker status.
AB - BACKGROUND: While a great deal of work has gone into understanding the
relationship between Cerebrospinal fluid (CSF) biomarkers, brain atrophy, and
disease progression, less work has attempted to investigate how genetic variation
modifies these relationships. The goal of this study was two-fold. First, we
sought to identify high-risk vs. low-risk individuals based on their CSF tau and
Abeta load and characterize these individuals with regard to brain atrophy in an
AD-relevant region of interest. Next, we sought to identify genetic variants that
modified the relationship between biomarker classification and neurodegeneration.
METHODS: Participants were categorized based on established cut-points for
biomarker positivity. Mixed model regression was used to quantify longitudinal
change in the left inferior lateral ventricle. Interaction analyses between
single nucleotide polymorphisms (SNPs) and biomarker group status were performed
using a genome wide association study (GWAS) approach. Correction for multiple
comparisons was performed using the Bonferroni procedure. RESULTS: One intergenic
SNP (rs4866650) and one SNP within the SPTLC1 gene (rs7849530) modified the
association between amyloid positivity and neurodegeneration. A transcript
variant of WDR11-AS1 gene (rs12261764) modified the association between tau
positivity and neurodegeneration. These effects were consistent across the two
sub-datasets and explained approximately 3% of variance in ventricular dilation.
One additional SNP (rs6887649) modified the association between amyloid
positivity and baseline ventricular volume, but was not observed consistently
across the sub-datasets. CONCLUSIONS: Genetic variation modifies the association
between AD biomarkers and neurodegeneration. Genes that regulate the molecular
response in the brain to oxidative stress may be particularly relevant to neural
vulnerability to the damaging effects of amyloid-beta.
PMID- 25140147
TI - Feature integration and object representations along the dorsal stream visual
hierarchy.
AB - THE VISUAL SYSTEM IS SPLIT INTO TWO PROCESSING STREAMS: a ventral stream that
receives color and form information and a dorsal stream that receives motion
information. Each stream processes that information hierarchically, with each
stage building upon the previous. In the ventral stream this leads to the
formation of object representations that ultimately allow for object recognition
regardless of changes in the surrounding environment. In the dorsal stream, this
hierarchical processing has classically been thought to lead to the computation
of complex motion in three dimensions. However, there is evidence to suggest that
there is integration of both dorsal and ventral stream information into motion
computation processes, giving rise to intermediate object representations, which
facilitate object selection and decision making mechanisms in the dorsal stream.
First we review the hierarchical processing of motion along the dorsal stream and
the building up of object representations along the ventral stream. Then we
discuss recent work on the integration of ventral and dorsal stream features that
lead to intermediate object representations in the dorsal stream. Finally we
propose a framework describing how and at what stage different features are
integrated into dorsal visual stream object representations. Determining the
integration of features along the dorsal stream is necessary to understand not
only how the dorsal stream builds up an object representation but also which
computations are performed on object representations instead of local features.
PMID- 25140152
TI - Glutathione levels modulation as a strategy in host-parasite interactions
insights for biology of cancer.
PMID- 25140150
TI - Structure activity relationship of phenolic acid inhibitors of alpha-synuclein
fibril formation and toxicity.
AB - The aggregation of alpha-synuclein (alpha-syn) is considered the key pathogenic
event in many neurological disorders such as Parkinson's disease (PD), dementia
with Lewy bodies and multiple system atrophy, giving rise to a whole category of
neurodegenerative diseases known as synucleinopathies. Although the molecular
basis of alpha-syn toxicity has not been precisely elucidated, a great deal of
effort has been put into identifying compounds that could inhibit or even reverse
the aggregation process. Previous reports indicated that many phenolic compounds
are potent inhibitors of alpha-syn aggregation. The aim of the present study was
to assess the anti-aggregating effect of gallic acid (GA) (3,4,5
trihydroxybenzoic acid), a benzoic acid derivative that belongs to a group of
phenolic compounds known as phenolic acids. By employing an array of biophysical
and biochemical techniques and a cell-viability assay, GA was shown not only to
inhibit alpha-syn fibrillation and toxicity but also to disaggregate preformed
alpha-syn amyloid fibrils. Interestingly, GA was found to bind to soluble, non
toxic oligomers with no beta-sheet content, and to stabilize their structure. The
binding of GA to the oligomers may represent a potential mechanism of action.
Additionally, by using structure activity relationship data obtained from
fourteen structurally similar benzoic acid derivatives, it was determined that
the inhibition of alpha-syn fibrillation by GA is related to the number of
hydroxyl moieties and their position on the phenyl ring. GA may represent the
starting point for designing new molecules that could be used for the treatment
of PD and related disorders.
PMID- 25140151
TI - Age-Dependent Modifications of AMPA Receptor Subunit Expression Levels and
Related Cognitive Effects in 3xTg-AD Mice.
AB - GluA1, GluA2, GluA3, and GluA4 are the constitutive subunits of amino-3-hydroxy-5
methyl-4-isoxazolepropionic acid receptors (AMPARs), the major mediators of fast
excitatory transmission in the mammalian central nervous system. Most AMPARs are
Ca(2+)-impermeable because of the presence of the GluA2 subunit. GluA2 mRNA
undergoes an editing process that results in a Q-R substitution, a key factor in
the regulation of AMPAR Ca(2+)-permeability. AMPARs lacking GluA2 or containing
the unedited subunit are permeable to Ca(2+) and Zn(2+). The phenomenon
physiologically modulates synaptic plasticity while, in pathologic conditions,
leads to increased vulnerability to excitotoxic neuronal death. Given the
importance of these subunits, we have therefore evaluated possible associations
between changes in expression levels of AMPAR subunits and development of
cognitive deficits in 3xTg-AD mice, a widely investigated transgenic mouse model
of Alzheimer's disease (AD). With quantitative real-time PCR analysis, we assayed
hippocampal mRNA expression levels of GluA1-4 subunits occurring in young [3
months of age (m.o.a.)] and old (12 m.o.a) Tg-AD mice and made comparisons with
levels found in age-matched wild type (WT) mice. Efficiency of GluA2 RNA editing
was also analyzed. All animals were cognitively tested for learning short- and
long-term spatial memory with the Morris Water Maze (MWM) navigation task. 3xTg
AD mice showed age-dependent decreases of mRNA levels for all the AMPAR subunits,
with the exception of GluA2. Editing remained fully efficient with aging in 3xTg
AD and WT mice. A one-to-one correlation analysis between MWM performances and
GluA1-4 mRNA expression profiles showed negative correlations between GluA2
levels and MWM performances in young 3xTg-AD mice. On the contrary, positive
correlations between GluA2 mRNA and MWM performances were found in young WT mice.
Our data suggest that increases of AMPARs that contain GluA1, GluA3, and GluA4
subunits may help in maintaining cognition in pre-symptomatic 3xTg-AD mice.
PMID- 25140153
TI - Expression pattern of glycoside hydrolase genes in Lutzomyia longipalpis reveals
key enzymes involved in larval digestion.
AB - The sand fly Lutzomyia longipalpis is the most important vector of American
Visceral Leishmaniasis. Adults are phytophagous (males and females) or blood
feeders (females only), and larvae feed on solid detritus. Digestion in sand fly
larvae has scarcely been studied, but some glycosidase activities putatively
involved in microorganism digestion were already described. Nevertheless, the
molecular nature of these enzymes, as the corresponding genes and transcripts,
were not explored yet. Catabolism of microbial carbohydrates in insects generally
involves beta-1,3-glucanases, chitinases, and digestive lysozymes. In this work,
the transcripts of digestive beta-1,3-glucanase and chitinases were identified in
the L. longipalpis larvae throughout analysis of sequences and expression
patterns of glycoside hydrolases families 16, 18, and 22. The activity of one i
type lysozyme was also registered. Interestingly, this lysozyme seems to play a
role in immunity, rather than digestion. This is the first attempt to identify
the molecular nature of sand fly larval digestive enzymes.
PMID- 25140154
TI - S-acylation dependent post-translational cross-talk regulates large conductance
calcium- and voltage- activated potassium (BK) channels.
AB - Mechanisms that control surface expression and/or activity of large conductance
calcium-activated potassium (BK) channels are important determinants of their
(patho)physiological function. Indeed, BK channel dysfunction is associated with
major human disorders ranging from epilepsy to hypertension and obesity. S
acylation (S-palmitoylation) represents a major reversible, post-translational
modification controlling the properties and function of many proteins including
ion channels. Recent evidence reveals that both pore-forming and regulatory
subunits of BK channels are S-acylated and control channel trafficking and
regulation by AGC-family protein kinases. The pore-forming alpha-subunit is S
acylated at two distinct sites within the N- and C-terminus, each site being
regulated by different palmitoyl acyl transferases (zDHHCs) and acyl
thioesterases (APTs). S-acylation of the N-terminus controls channel trafficking
and surface expression whereas S-acylation of the C-terminal domain determines
regulation of channel activity by AGC-family protein kinases. S-acylation of the
regulatory beta4-subunit controls ER exit and surface expression of BK channels
but does not affect ion channel kinetics at the plasma membrane. Furthermore, a
significant number of previously identified BK-channel interacting proteins have
been shown, or are predicted to be, S-acylated. Thus, the BK channel multi
molecular signaling complex may be dynamically regulated by this fundamental post
translational modification and thus S-acylation likely represents an important
determinant of BK channel physiology in health and disease.
PMID- 25140156
TI - Differences in Aerobic Fitness between Inpatients and Outpatients with Severe
Mental Disorders.
AB - BACKGROUND: Patients with severe mental disorders have increased mortality, and
cardiovascular disease (CVD) accounts for a large part. Physical inactivity and
low aerobic fitness have been recognized as significant risk factors for CVD. In
this study, we investigated the differences in aerobic fitness and physical
activity between in- and outpatients with severe mental disorders. METHOD AND
SUBJECTS: Fifty in- and outpatients from a regional psychiatric department were
included. The patients filled in a questionnaire on physical activity and
completed a clinical examination. An estimation of aerobic fitness was calculated
for each patient, using gender, age, waist circumference, resting heart rate, and
physical activity level as variables. RESULTS: Inpatients had lower estimated
aerobic fitness than outpatients (VO2peak 42 vs. 50 mL kg(-1) min(-1), p <
0.001). Compared to population data matched for age and gender, inpatients had
lower aerobic fitness, while outpatients were not different from the population
average. CONCLUSION: Inpatients at a psychiatric department had lower estimated
aerobic fitness than outpatients, and a lower aerobic fitness compared to the
general population. Our findings suggest that inpatients with severe mental
disorders should be considered a high risk group for CVD.
PMID- 25140157
TI - NR2B Antagonist CP-101,606 Abolishes Pitch-Mediated Deviance Detection in Awake
Rats.
AB - Schizophrenia patients exhibit a decreased ability to detect change in their
auditory environment as measured by auditory event-related potentials (ERP) such
as mismatch negativity. This deficit has been linked to abnormal NMDA
neurotransmission since, among other observations, non-selective channel blockers
of NMDA reliably diminish automatic deviance detection in human subjects as well
as in animal models. Recent molecular and functional evidence links NR2B receptor
subtype to aberrant NMDA transmission in schizophrenia. However, it is unknown if
NR2B receptors participate in pre-attentive deviance detection. We recorded ERP
from the vertex of freely behaving rats in response to frequency mismatch
protocols. We saw a robust increase in N1 response to deviants compared to
standard as well as control stimuli indicating true deviance detection. Moreover,
the increased negativity was highly sensitive to deviant probability. Next, we
tested the effect of a non-selective NMDA channel blocker (ketamine, 30 mg/kg)
and a highly selective NR2B antagonist, CP-101,606 (10 or 30 mg/kg) on deviance
detection. Ketamine attenuated deviance mainly by increasing the amplitude of the
standard ERP. Amplitude and/or latency of several ERP components were also
markedly affected. In contrast, CP-101,606 robustly and dose-dependently
inhibited the deviant's N1 amplitude, and as a consequence, completely abolished
deviance detection. No other ERPs or components were affected. Thus, we report
first evidence that NR2B receptors robustly participate in processes of automatic
deviance detection in a rodent model. Lastly, our model demonstrates a path
forward to test specific pharmacological hypotheses using translational endpoints
relevant to aberrant sensory processing in schizophrenia.
PMID- 25140155
TI - Systemic and renal oxidative stress in the pathogenesis of hypertension:
modulation of long-term control of arterial blood pressure by resveratrol.
AB - Hypertension affects over 25% of the global population and is associated with
grave and often fatal complications that affect many organ systems. Although
great advancements have been made in the clinical assessment and treatment of
hypertension, the cause of hypertension in over 90% of these patients is unknown,
which hampers the development of targeted and more effective treatment. The
etiology of hypertension involves multiple pathological processes and organ
systems, however one unifying feature of all of these contributing factors is
oxidative stress. Once the body's natural anti-oxidant defense mechanisms are
overwhelmed, reactive oxygen species (ROS) begin to accumulate in the tissues.
ROS play important roles in normal regulation of many physiological processes,
however in excess they are detrimental and cause widespread cell and tissue
damage as well as derangements in many physiological processes. Thus, control of
oxidative stress has become an attractive target for pharmacotherapy to prevent
and manage hypertension. Resveratrol (trans-3,5,4'-Trihydroxystilbene) is a
naturally occurring polyphenol which has anti-oxidant effects in vivo. Many
studies have shown anti-hypertensive effects of resveratrol in different pre
clinical models of hypertension, via a multitude of mechanisms that include its
function as an anti-oxidant. However, results have been mixed and in some cases
resveratrol has no effect on blood pressure. This may be due to the heavy
emphasis on peripheral vasodilator effects of resveratrol and virtually no
investigation of its potential renal effects. This is particularly troubling in
the arena of hypertension, where it is well known and accepted that the kidney
plays an essential role in the long term regulation of arterial pressure and a
vital role in the initiation, development and maintenance of chronic
hypertension. It is thus the focus of this review to discuss the potential of
resveratrol as an anti-hypertensive treatment via amelioration of oxidative
stress within the framework of the fundamental physiological principles of long
term regulation of arterial blood pressure.
PMID- 25140158
TI - Network based statistical analysis detects changes induced by continuous theta
burst stimulation on brain activity at rest.
AB - We combined continuous theta-burst stimulation (cTBS) and resting state (RS)-fMRI
approaches to investigate changes in functional connectivity (FC) induced by
right dorsolateral prefrontal cortex (DLPFC)-cTBS at rest in a group of healthy
subjects. Seed-based fMRI analysis revealed a specific pattern of correlation
between the right prefrontal cortex and several brain regions: based on these
results, we defined a 29-node network to assess changes in each network
connection before and after, respectively, DLPFC-cTBS and sham sessions. A
decrease of correlation between the right prefrontal cortex and right parietal
cortex (Brodmann areas 46 and 40, respectively) was detected after cTBS, while no
significant result was found when analyzing sham-session data. To our knowledge,
this is the first study that demonstrates within-subject changes in FC induced by
cTBS applied on prefrontal area. The possibility to induce selective changes in a
specific region without interfering with functionally correlated area could have
several implications for the study of functional properties of the brain, and for
the emerging therapeutic strategies based on transcranial stimulation.
PMID- 25140160
TI - Visual relations children find easy and difficult to process in figural
analogies.
AB - Analogical reasoning, the ability to learn about novel phenomena by relating it
to structurally similar knowledge, develops with great variability in children.
Furthermore, the development of analogical reasoning coincides with greater
working memory efficiency and increasing knowledge of the entities and relations
present in analogy problems. In figural matrices, a classical form of analogical
reasoning assessment, some features, such as color, appear easier for children to
encode and infer than others, such as orientation. Yet, few studies have
structurally examined differences in the difficulty of visual relations across
different age-groups. This cross-sectional study of figural analogical reasoning
examined which underlying rules in figural analogies were easier or more
difficult for children to correctly process. School children (N = 1422, M = 7.0
years, SD = 21 months, range 4.5-12.5 years) were assessed in analogical
reasoning using classical figural matrices and memory measures. The visual
relations the children had to induce and apply concerned the features: animal,
color, orientation, position, quantity and size. The role of age and memory span
on the children's ability to correctly process each type of relation was examined
using explanatory item response theory models. The results showed that with
increasing age and/or greater memory span all visual relations were processed
more accurately. The "what" visual relations animal, color, quantity and size
were easiest, whereas the "where" relations orientation and position were most
difficult. However, the "where" visual relations became relatively easier with
age and increased memory efficiency. The implications are discussed in terms of
the development of visual processing in object recognition vs. position and
motion encoding in the ventral ("what") and dorsal ("where") pathways
respectively.
PMID- 25140159
TI - The biological function of consciousness.
AB - This research is an investigation of whether consciousness-one's ongoing
experience-influences one's behavior and, if so, how. Analysis of the components,
structure, properties, and temporal sequences of consciousness has established
that, (1) contrary to one's intuitive understanding, consciousness does not have
an active, executive role in determining behavior; (2) consciousness does have a
biological function; and (3) consciousness is solely information in various
forms. Consciousness is associated with a flexible response mechanism (FRM) for
decision-making, planning, and generally responding in nonautomatic ways. The FRM
generates responses by manipulating information and, to function effectively, its
data input must be restricted to task-relevant information. The properties of
consciousness correspond to the various input requirements of the FRM; and when
important information is missing from consciousness, functions of the FRM are
adversely affected; both of which indicate that consciousness is the input data
to the FRM. Qualitative and quantitative information (shape, size, location,
etc.) are incorporated into the input data by a qualia array of colors, sounds,
and so on, which makes the input conscious. This view of the biological function
of consciousness provides an explanation why we have experiences; why we have
emotional and other feelings, and why their loss is associated with poor decision
making; why blindsight patients do not spontaneously initiate responses to events
in their blind field; why counter-habitual actions are only possible when the
intended action is in mind; and the reason for inattentional blindness.
PMID- 25140161
TI - Phonological and lexical influences on phonological awareness in children with
specific language impairment and dyslexia.
AB - Children with dyslexia and/or specific language impairment have marked deficits
in phonological processing, putting them at an increased risk for reading
deficits. The current study sought to examine the influence of word-level
phonological and lexical characteristics on phonological awareness. Children with
dyslexia and/or specific language impairment were tested using a phoneme deletion
task in which stimuli differed orthogonally by sound similarity and neighborhood
density. Phonological and lexical factors influenced performance differently
across groups. Children with dyslexia appeared to have a more immature and
aberrant pattern of phonological and lexical influence (e.g., favoring sparse and
similar features). Children with SLI performed less well than children who were
typically developing, but followed a similar pattern of performance (e.g.,
favoring dense and dissimilar features). Collectively, our results point to both
quantitative and qualitative differences in lexical organization and phonological
representations in children with SLI and in children with dyslexia.
PMID- 25140162
TI - Distortion of auditory space during visually induced self-motion in depth.
AB - Perception of self-motion is based on the integration of multiple sensory inputs,
in particular from the vestibular and visual systems. Our previous study
demonstrated that vestibular linear acceleration information distorted auditory
space perception (Teramoto et al., 2012). However, it is unclear whether this
phenomenon is contingent on vestibular signals or whether it can be caused by
inputs from other sensory modalities involved in self-motion perception. Here, we
investigated whether visual linear self-motion information can also alter
auditory space perception. Large-field visual motion was presented to induce self
motion perception with constant accelerations (Experiment 1) and a constant
velocity (Experiment 2) either in a forward or backward direction. During
participants' experience of self-motion, a short noise burst was delivered from
one of the loudspeakers aligned parallel to the motion direction along a wall to
the left of the listener. Participants indicated from which direction the sound
was presented, forward or backward, relative to their coronal (i.e., frontal)
plane. Results showed that the sound position aligned with the subjective coronal
plane (SCP) was significantly displaced in the direction of self-motion,
especially in the backward self-motion condition as compared with a no motion
condition. These results suggest that self-motion information, irrespective of
its origin, is crucial for auditory space perception.
PMID- 25140163
TI - The role of ANS acuity and numeracy for the calibration and the coherence of
subjective probability judgments.
AB - The purpose of the study was to investigate how numeracy and acuity of the
approximate number system (ANS) relate to the calibration and coherence of
probability judgments. Based on the literature on number cognition, a first
hypothesis was that those with lower numeracy would maintain a less linear use of
the probability scale, contributing to overconfidence and nonlinear calibration
curves. A second hypothesis was that also poorer acuity of the ANS would be
associated with overconfidence and non-linearity. A third hypothesis, in line
with dual-systems theory (e.g., Kahneman and Frederick, 2002) was that people
higher in numeracy should have better access to the normative probability rules,
allowing them to decrease the rate of conjunction fallacies. Data from 213
participants sampled from the Swedish population showed that: (i) in line with
the first hypothesis, overconfidence and the linearity of the calibration curves
were related to numeracy, where people higher in numeracy were well calibrated
with zero overconfidence. (ii) ANS was not associated with overconfidence and non
linearity, disconfirming the second hypothesis. (iii) The rate of conjunction
fallacies was slightly, but to a statistically significant degree decreased by
numeracy, but still high at all numeracy levels. An unexpected finding was that
participants with better ANS acuity gave more realistic estimates of their
performance relative to others.
PMID- 25140164
TI - Use of the adult attachment projective picture system in psychodynamic
psychotherapy with a severely traumatized patient.
AB - The following case study is presented to facilitate an understanding of how the
attachment information evident from Adult Attachment Projective Picture System
(AAP) assessment can be integrated into a psychodynamic perspective in making
therapeutic recommendations that integrate an attachment perspective. The Adult
Attachment Projective Picture System (AAP) is a valid representational measure of
internal representations of attachment based on the analysis of a set of free
response picture stimuli designed to systematically activate the attachment
system (George and West, 2012). The AAP provides a fruitful diagnostic tool for
psychodynamic-oriented clinicians to identify attachment-based deficits and
resources for an individual patient in therapy. This paper considers the use of
the AAP with a traumatized patient in an inpatient setting and uses a case study
to illustrate the components of the AAP that are particularly relevant to a
psychodynamic conceptualization. The paper discusses also attachment-based
recommendations for intervention.
PMID- 25140165
TI - Pharmacological Treatments Inhibiting Levodopa-Induced Dyskinesias in MPTP
Lesioned Monkeys: Brain Glutamate Biochemical Correlates.
AB - Anti-glutamatergic drugs can relieve Parkinson's disease (PD) symptoms and
decrease l-3,4-dihydroxyphenylalanine (l-DOPA)-induced dyskinesias (LID). This
review reports relevant studies investigating glutamate receptor subtypes in
relation to motor complications in PD patients and 1-methyl-4-phenyl-1,2,3,6
tetrahydropyridine (MPTP)-lesioned monkeys. Antagonists of the ionotropic
glutamate receptors, such as N-methyl-d-aspartate (NMDA) and alpha-amino-3
hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, display
antidyskinetic activity in PD patients and animal models such as the MPTP monkey.
Metabotropic glutamate 5 (mGlu5) receptor antagonists were shown to reduce the
severity of LID in PD patients as well as in already dyskinetic non-human
primates and to prevent the development of LID in de novo treatments in non-human
primates. An increase in striatal post-synaptic NMDA, AMPA, and mGlu5 receptors
is documented in PD patients and MPTP monkeys with LID. This increase can be
prevented in MPTP monkeys with the addition of a specific glutamate receptor
antagonist to the l-DOPA treatment and also with drugs of various pharmacological
specificities suggesting multiple receptor interactions. This is yet to be well
documented for presynaptic mGlu4 and mGlu2/3 and offers additional new promising
avenues.
PMID- 25140167
TI - Grappling archaea: ultrastructural analyses of an uncultivated, cold-loving
archaeon, and its biofilm.
AB - Similarly to Bacteria, Archaea are microorganisms that interact with their
surrounding environment in a versatile manner. To date, interactions based on
cellular structure and surface appendages have mainly been documented using model
systems of cultivable archaea under laboratory conditions. Here, we report on the
microbial interactions and ultrastructural features of the uncultivated SM1
Euryarchaeon, which is highly dominant in its biotope. Therefore, biofilm samples
taken from the Sippenauer Moor, Germany, were investigated via transmission
electron microscopy (TEM; negative staining, thin-sectioning) and scanning
electron microscopy (SEM) in order to elucidate the fine structures of the
microbial cells and the biofilm itself. The biofilm consisted of small archaeal
cocci (0.6 MUm diameter), arranged in a regular pattern (1.0-2.0 MUm distance
from cell to cell), whereas each archaeon was connected to 6 other archaea on
average. Extracellular polymeric substances (EPS) were limited to the close
vicinity of the archaeal cells, and specific cell surface appendages (hami,
Moissl et al., 2005) protruded beyond the EPS matrix enabling microbial
interaction by cell-cell contacts among the archaea and between archaea and
bacteria. All analyzed hami revealed their previously described architecture of
nano-grappling hooks and barb-wire basal structures. Considering the archaeal
cell walls, the SM1 Euryarchaea exhibited a double-membrane, which has rarely
been reported for members of this phylogenetic domain. Based on these findings,
the current generalized picture on archaeal cell walls needs to be revisited, as
archaeal cell structures are more complex and sophisticated than previously
assumed, particularly when looking into the uncultivated majority.
PMID- 25140168
TI - Halophilic Aspergillus penicillioides from athalassohaline, thalassohaline, and
polyhaline environments.
AB - Aspergillus penicillioides is a true halophile, present in diverse econiches -
from the hypersaline athalassohaline, and thalassohaline environments, to
polyhaline systems, and in different geographical locations. Twenty seven
isolates from these environments, were seen to be moderate halophiles, euryhaline
in nature. They had an obligate need of a low aw and were unable to grow on a
regular defined medium such as Czapek Dox Agar, as well as on varied nutrient
rich agar media such as Malt Extract, Potato Dextrose and Sabouraud Agar;
however, growth was obtained on all these media when amended with 10% solar salt.
In absence of added salt, the conidia either did not germinate, or when
germinated, distortions and lysis were seen in the short mycelial forms; on media
with salt, the mycelia and vesicles appeared normal.
PMID- 25140166
TI - ER stress, autophagy, and RNA viruses.
AB - Endoplasmic reticulum (ER) stress is a general term for representing the pathway
by which various stimuli affect ER functions. ER stress induces the
evolutionarily conserved signaling pathways, called the unfolded protein response
(UPR), which compromises the stimulus and then determines whether the cell
survives or dies. In recent years, ongoing research has suggested that these
pathways may be linked to the autophagic response, which plays a key role in the
cell's response to various stressors. Autophagy performs a self-digestion
function, and its activation protects cells against certain pathogens. However,
the link between the UPR and autophagy may be more complicated. These two systems
may act dependently, or the induction of one system may interfere with the other.
Experimental studies have found that different viruses modulate these mechanisms
to allow them to escape the host immune response or, worse, to exploit the host's
defense to their advantage; thus, this topic is a critical area in antiviral
research. In this review, we summarize the current knowledge about how RNA
viruses, including influenza virus, poliovirus, coxsackievirus, enterovirus 71,
Japanese encephalitis virus, hepatitis C virus, and dengue virus, regulate these
processes. We also discuss recent discoveries and how these will produce novel
strategies for antiviral treatment.
PMID- 25140169
TI - A Question of Nature: Some Antigens are Bound to be Allergens.
PMID- 25140171
TI - Structural divergence and loss of phosphoinositide-specific phospholipase C
signaling components during the evolution of the green plant lineage:
implications from structural characteristics of algal components.
PMID- 25140172
TI - Appearance traits in fish farming: progress from classical genetics to genomics,
providing insight into current and potential genetic improvement.
AB - Appearance traits in fish, those external body characteristics that influence
consumer acceptance at point of sale, have come to the forefront of commercial
fish farming, as culture profitability is closely linked to management of these
traits. Appearance traits comprise mainly body shape and skin pigmentation.
Analysis of the genetic basis of these traits in different fish reveals
significant genetic variation within populations, indicating potential for their
genetic improvement. Work into ascertaining the minor or major genes underlying
appearance traits for commercial fish is emerging, with substantial progress in
model fish in terms of identifying genes that control body shape and skin colors.
In this review, we describe research progress to date, especially with regard to
commercial fish, and discuss genomic findings in model fish in order to better
address the genetic basis of the traits. Given that appearance traits are
important in commercial fish, the genomic information related to this issue
promises to accelerate the selection process in coming years.
PMID- 25140170
TI - Maize transformation technology development for commercial event generation.
AB - Maize is an important food and feed crop in many countries. It is also one of the
most important target crops for the application of biotechnology. Currently,
there are more biotech traits available on the market in maize than in any other
crop. Generation of transgenic events is a crucial step in the development of
biotech traits. For commercial applications, a high throughput transformation
system producing a large number of high quality events in an elite genetic
background is highly desirable. There has been tremendous progress in
Agrobacterium-mediated maize transformation since the publication of the Ishida
et al. (1996) paper and the technology has been widely adopted for transgenic
event production by many labs around the world. We will review general efforts in
establishing efficient maize transformation technologies useful for transgenic
event production in trait research and development. The review will also discuss
transformation systems used for generating commercial maize trait events
currently on the market. As the number of traits is increasing steadily and two
or more modes of action are used to control key pests, new tools are needed to
efficiently transform vectors containing multiple trait genes. We will review
general guidelines for assembling binary vectors for commercial transformation.
Approaches to increase transformation efficiency and gene expression of large
gene stack vectors will be discussed. Finally, recent studies of targeted genome
modification and transgene insertion using different site-directed nuclease
technologies will be reviewed.
PMID- 25140173
TI - Hypothesis: genetic and epigenetic risk factors interact to modulate
vulnerability and resilience to FASD.
AB - Fetal alcohol spectrum disorder (FASD) presents a collection of symptoms
representing physiological and behavioral phenotypes caused by maternal alcohol
consumption. Symptom severity is modified by genetic differences in fetal
susceptibility and resistance as well as maternal genetic factors such as
maternal alcohol sensitivity. Animal models demonstrate that both maternal and
paternal genetics contribute to the variation in the fetus' vulnerability to
alcohol exposure. Maternal and paternal genetics define the variations in these
phenotypes even without the effect of alcohol in utero, as most of these traits
are polygenic, non-Mendelian, in their inheritance. In addition, the epigenetic
alterations that instigate the alcohol induced neurodevelopmental deficits can
interact with the polygenic inheritance of respective traits. Here, based on
specific examples, we present the hypothesis that the principles of non-Mendelian
inheritance, or "exceptions" to Mendelian genetics, can be the driving force
behind the severity of the prenatal alcohol-exposed individual's symptomology.
One such exception is when maternal alleles lead to an altered intrauterine
hormonal environment and, therefore, produce variations in the long-term
consequences on the development of the alcohol-exposed fetus. Another exception
is when epigenetic regulation of allele-specific gene expression generates
disequilibrium between the maternal vs. paternal genetic contributions, and
thereby, modifies the effect of prenatal alcohol exposure on the fetus. We
propose that these situations in which one parent has an exaggerated influence
over the offspring's vulnerability to prenatal alcohol are major contributing
mechanisms responsible for the variations in the symptomology of FASD in the
exposed generation and beyond.
PMID- 25140174
TI - Thalassophryne nattereri fish venom: from the envenoming to the understanding of
the immune system.
AB - Thalassophryne nattereri (niquim) is a venomous fish found off North and
Northeast coast of Brazil, where it is known by the severity of the accidents
involving humans. This review article is divided into four topics. The first one
provides a brief description of the animal biology and its distribution off
Brazilian coastal waters, the venom apparatus, signs and symptoms observed in
envenomated humans and also describes envenomation in mice. The second topic
describes the use of modern genetic approach and mass spectrometry for
identification of highly expressed genes in its venom glands and the sequence of
major toxins. The third chapter offers a detailed study of tissue injury induced
by the venom and reveals the role of toxins that impair inflammation reduction.
Finally, the fourth section expands the understanding of many extrinsic and
intrinsic essential factors in maintaining survival of memory B cell compartment.
Our results demonstrate the wide possibilities for research in the area of
toxinology, also the necessity of interconnection among biochemistry,
pharmacology and immunology areas for the expansion of knowledge and for
generation of innovation.
PMID- 25140175
TI - Multidrug resistance: an emerging crisis.
AB - The resistance among various microbial species (infectious agents) to different
antimicrobial drugs has emerged as a cause of public health threat all over the
world at a terrifying rate. Due to the pacing advent of new resistance mechanisms
and decrease in efficiency of treating common infectious diseases, it results in
failure of microbial response to standard treatment, leading to prolonged
illness, higher expenditures for health care, and an immense risk of death.
Almost all the capable infecting agents (e.g., bacteria, fungi, virus, and
parasite) have employed high levels of multidrug resistance (MDR) with enhanced
morbidity and mortality; thus, they are referred to as "super bugs." Although the
development of MDR is a natural phenomenon, the inappropriate use of
antimicrobial drugs, inadequate sanitary conditions, inappropriate food-handling,
and poor infection prevention and control practices contribute to emergence of
and encourage the further spread of MDR. Considering the significance of MDR,
this paper, emphasizes the problems associated with MDR and the need to
understand its significance and mechanisms to combat microbial infections.
PMID- 25140177
TI - Increased incidence of thyroid dysfunction and autoimmunity in patients with
vernal keratoconjunctivitis.
AB - Hormones may play a role in the pathophysiology of vernal keratoconjunctivitis
(VKC). An increased incidence of thyroid autoantibodies was recently observed in
VKC, although there were no data on thyroid function. Two hundred and eighty
eight patients (202 males, 86 females; range 5.5 to 16.9 years) with VKC were
evaluated and compared with 188 normal age- and sex-matched subjects. In all
subjects, serum concentrations of free T4, TSH, thyroperoxidase, thyroglobulin,
and TSHr autoantibodies were evaluated. In VKC, the family history of thyroid
diseases showed no significant differences compared to the controls (9.4 versus
8.6%), whereas the family history of autoimmune diseases was significantly higher
(13.2% versus 6.3%; P<0.05). Subclinical hypothyroidism was diagnosed in 6.6%
(versus 1.6% of the controls; P<0.05) and overt hypothyroidism in 0.7% (versus
0.0% of the controls; P = NS). Finally, 5.2% of patients were positive for
thyroid autoantibodies, which were significantly higher with respect to the
controls (0.5%, P<0.05). In the patients positive for thyroid autoantibodies, 80%
showed a sonography pattern that suggested autoimmune thyroiditis. Thyroid
function and autoimmunity abnormalities are frequently present in children with
VKC. Children with VKC should be screened for thyroid function and evaluated for
thyroid autoimmunity.
PMID- 25140178
TI - Concomitant factors leading to an atypical osteonecrosis of the jaw in a patient
with multiple myeloma.
AB - Osteonecrosis of the jaw (ONJ) is a site specific osseous pathology,
characterized by chronic exposed bone in the mouth, which needs to be reinforced
periodically within the medical literature. ONJ is a clinical entity with many
possible aetiologies and its pathogenesis is not well understood. The risk
factors for ONJ include bisphosphonates treatments, head and neck radiotherapy,
dental procedures involving bone surgery, and trauma. Management of ONJ has
centred on efforts to eliminate or reduce severity of symptoms, to slow or
prevent the progression of disease, and to eradicate diseased bone. This case
describes a rare case of ONJ in a 64-year-old Caucasian male diagnosed with
multiple myeloma stage III. The lesion was related to a traumatic injury during
mastication. Eighteen months ago in the same area the molar 37 was extracted,
achieving a complete satisfactory healing, when only 2 doses of zoledronic acid
had been administered. Actinomyces bacterial aggregates were also identified in
the microscopic analysis. The management of this osteonecrotic lesion included
antibiotic treatment and chlorhexidine topical gel administration. The evolution
was monitored every two weeks until patient's death. The authors provide a
discussion of the etiology, pathogenesis, diagnosis, and management. This case
report may shed light on the controversies about concomitant factors and
mechanisms inducing ONJ.
PMID- 25140179
TI - Laryngeal lymphoma: the high and low grades of rare lymphoma involvement sites.
AB - The larynx is an extremely rare site of involvement by lymphomatous disease. We
present two cases of isolated laryngeal high-grade and another low-grade
lymphoma, together with a literature review of laryngeal lymphoma management.
PMID- 25140180
TI - Acute zonal occult outer retinopathy with atypical findings.
AB - Background. To report a case of acute zonal occult outer retinopathy (AZOOR) with
atypical electrophysiology findings. Case Presentation. A 23-year-old-female
presented with visual acuity deterioration in her right eye accompanied by
photopsia bilaterally. Corrected distance visual acuity at presentation was 20/50
in the right eye and 20/20 in the left eye. Fundus examination was unremarkable.
Visual field (VF) testing revealed a large scotoma. Pattern and full-field
electroretinograms (PERG and ERG) revealed macular involvement associated with
generalized retinal dysfunction. Electrooculogram (EOG) light rise and the Arden
ratio were within normal limits bilaterally. The patient was diagnosed with AZOOR
due to clinical findings, visual field defect, and ERG findings. Conclusion. This
is a case of AZOOR with characteristic VF defects and clinical symptoms
presenting with atypical EOG findings.
PMID- 25140181
TI - Acute rhabdomyolysis associated with coadministration of levofloxacin and
simvastatin in a patient with normal renal function.
AB - We report a rare case of severe acute rhabdomyolysis in association with
coadministration of levofloxacin and simvastatin in a patient with normal renal
function. A 70-year-old Caucasian male was treated due to community acquired
pneumonia with levofloxacin in a dosage of 500 mg once and then twice a day. On
the 8th day of hospitalization the patient presented with acute severe
rhabdomyolysis requiring an intensive care support. After discontinuation of
levofloxacin and concomitant medication with simvastatin 80 mg/day, clinical and
laboratory effects were totally reversible. Up to now, levofloxacin has been
reported to induce rhabdomyolysis mainly in patients with impaired renal
function, as the medication has a predominant renal elimination. In our case
renal function remained normal during the severe clinical course. According to a
recent case report rhabdomyolysis was observed due to interaction of simvastatin
and ciprofloxacin. To our best knowledge this is the first case of interaction
between simvastatin and levofloxacin to be reported. This case emphasizes the
need of close monitoring of creatine kinase in patients under more than one
potentially myotoxic medication especially when patients develop muscle weakness.
PMID- 25140182
TI - Bilateral Upper Extremity DVT in a 43-Year-Old Man: Is It Thoracic Outlet
Syndrome?!
AB - Recurrent deep venous thrombosis, involving bilateral upper extremities, is an
extremely rare phenomenon. We are presenting a 43-year-old man who was diagnosed
with left upper extremity deep vein thrombosis (UEDVT) and was treated with
anticoagulation and surgical decompression in 2004. 9 years later, he presented
with right arm swelling and was diagnosed with right UEDVT using US venous
Doppler. Venogram showed compression of the subclavian vein by the first rib,
diagnosing thoracic outlet syndrome (TOS). He was treated with anticoagulation
and local venolysis and later by surgical decompression of the subclavian vein.
Bilateral UEDVT, as mentioned above, is an extremely rare condition that is
uncommonly caused by TOS. To our knowledge, we are reporting the first case of
bilateral UEDVT due to TOS. Diagnosis usually starts with US venous Doppler to
detect the thrombosis, followed by the gold standard venogram to locate the area
of obstruction and lyse the thrombus if needed. The ultimate treatment for TOS
remains surgical decompression of the vascular bundle at the thoracic outlet.
PMID- 25140183
TI - Challenges and frugal remedies for lowering facility based neonatal mortality and
morbidity: a comparative study.
AB - Millennium development goal target on infant mortality (MDG4) by 2015 would not
be realised in some low-resource countries. This was in part due to unsustainable
high-tech ideas that have been poorly executed. Prudent but high impact
techniques could have been synthesised in these countries. A collaborative
outreach was initiated to devise frugal measures that could reduce neonatal
deaths in Nigeria. Prevailing issues of concern that could militate against
neonatal survival within care centres were identified and remedies were
proffered. These included application of (i) recycled incubator technology (RIT)
as a measure of providing affordable incubator sufficiency, (ii) facility-based
research groups, (iii) elective training courses for clinicians/nurses, (iv)
independent local artisans on spare parts production, (v) power-banking and
apnoea-monitoring schemes, and (v) 1/2 yearly failure-preventive maintenance and
auditing system. Through a retrospective data analyses 4 outreach centres and one
"control" were assessed. Average neonatal mortality of centres reduced from
254/1000 to 114/1000 whilst control remained at 250/1000. There was higher
relative influx of incubator-dependent-neonates at outreach centres. It was found
that 43% of mortality occurred within 48 hours of presentation (d48) and up to
92% of d48 were of very-low birth parameters. The RIT and associated concerns
remedies have demonstrated the vital signs of efficiency that would have
guaranteed MDG4 neonatal component in Nigeria.
PMID- 25140184
TI - Neuroprotective effects of cuscutae semen in a mouse model of Parkinson's
disease.
AB - Parkinson's disease (PD) is a neurodegenerative movement disorder that is
characterized by the progressive degeneration of the dopaminergic (DA) pathway. 1
Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes damage to the DA
neurons, and 1-4-methyl-4-phenylpyridinium (MPP(+)) causes cell death in
differentiated PC12 cells that is similar to the degeneration that occurs in PD.
Moreover, MPTP treatment increases the activity of the brain's immune cells,
reactive oxygen species- (ROS-) generating processes, and glutathione peroxidase.
We recently reported that Cuscutae Semen (CS), a widely used traditional herbal
medicine, increases cell viability in a yeast model of PD. In the present study,
we examined the inhibitory effect of CS on the neurotoxicity of MPTP in mice and
on the MPP+-induced cell death in differentiated PC12 cells. The MPTP-induced
loss of nigral DA neurons was partly inhibited by CS-mediated decreases in ROS
generation. The activation of microglia was slightly inhibited by CS, although
this effect did not reach statistical significance. Furthermore, CS may reduce
the MPP+ toxicity in PC12 cells by suppressing glutathione peroxidase activation.
These results suggest that CS may be beneficial for the treatment of
neurodegenerative diseases such as PD.
PMID- 25140176
TI - The alliance of mesenchymal stem cells, bone, and diabetes.
AB - Bone fragility has emerged as a new complication of diabetes. Several mechanisms
in diabetes may influence bone homeostasis by impairing the action between
osteoblasts, osteoclasts, and osteocytes and/or changing the structural
properties of the bone tissue. Some of these mechanisms can potentially alter the
fate of mesenchymal stem cells, the initial precursor of the osteoblast. In this
review, we describe the main factors that impair bone health in diabetic patients
and their clinical impact.
PMID- 25140186
TI - Moxibustion Activates Macrophage Autophagy and Protects Experimental Mice against
Bacterial Infection.
AB - Moxibustion is one of main therapies in traditional Chinese medicine and uses
heat stimulation on the body surface from the burning of moxa to release pain or
treat diseases. Emerging studies have shown that moxibustion can generate
therapeutic effects by activating a series of signaling pathways and
neuroendocrine-immune activities. Here we show moxibustion promoted profound
macrophage autophagy in experimental Kunming mice, with reduced Akt
phosphorylation and activated eIF2alpha phosphorylation. Consequently,
moxibustion promoted bacterial clearance by macrophages and protected mice from
mortality due to bacterial infection. These results indicate that moxibustion
generates a protective response by activating autophagy against bacterial
infections.
PMID- 25140185
TI - A Metabonomics Profiling Study on Phlegm Syndrome and Blood-Stasis Syndrome in
Coronary Heart Disease Patients Using Liquid Chromatography/Quadrupole Time-of
Flight Mass Spectrometry.
AB - A metabonomics approach based on liquid chromatography/quadrupole time-of-flight
mass spectrometry (LC-Q-TOF/MS) was utilized to obtain potential biomarkers of
coronary heart disease (CHD) patients and investigate the ZHENG types
differentiation in CHD patients. The plasma samples of 20 CHD patients with
phlegm syndrome, 20 CHD patients with blood-stasis syndrome, and 16 healthy
volunteers were collected in the study. 26 potential biomarkers were identified
in the plasma of CHD patients and 19 differential metabolites contributed to the
discrimination of phlegm syndrome and blood-stasis syndrome in CHD patients (VIP
> 1.5; P < 0.05) which mainly involved purine metabolism, pyrimidine metabolism,
amino acid metabolism, steroid biosynthesis, and arachidonic acid metabolism.
This study demonstrated that metabonomics approach based on LC-MS was useful for
studying pathologic changes of CHD patients and interpreting the differentiation
of ZHENG types (phlegm and blood-stasis syndrome) in traditional Chinese medicine
(TCM).
PMID- 25140187
TI - Chemical Profiling of an Antimigraine Herbal Preparation, Tianshu Capsule, Based
on the Combination of HPLC, LC-DAD-MS (n) , and LC-DAD-ESI-IT-TOF/MS Analyses.
AB - Chemical profiling is always the first task in the standardization and
modernization of Traditional Chinese Medicine. HPLC and LC-MS were employed to
find out the common chromatographic peaks in various batches of Tianshu Capsule
(TSC) and the contribution of the characteristic peaks from individual herbs to
the whole chromatographic profile of TSC sample. A total of 38 constituents were
identified in TSC sample based on the comparison of retention time and UV spectra
with authentic compounds as well as by summarized MS fragmentation rules and
matching of empirical molecular formula with those of published components. This
is the first systematic report on the chemical profiling of the commercial TSC
product, which provides the sufficiently chemical evidence for the global quality
evaluation of TSC products.
PMID- 25140188
TI - Investigation of hepatic blood perfusion by laser speckle imaging and changes of
hepatic vasoactive substances in mice after electroacupuncture.
AB - The study was conducted to observe the effect of electroacupuncture (EA) on
hepatic blood perfusion (HBP) and vascular regulation. We investigated 60 male
anesthetized mice under the following 3 conditions: without EA stimulation
(control group); EA stimulation at Zusanli (ST36 group); EA stimulation at
nonacupoint (NA group) during 30 min. The HBP was measured using the laser
speckle perfusion imaging (LSPI). The level of nitric oxide (NO), endothelin-1
(ET-1), and noradrenaline (NE) in liver tissue was detected by biochemical
methods. Results were as follows. At each time point, HBP increase in ST36 group
was higher than that in the NA group in anesthetized mice. HBP gradually
decreased during 30 min in control group. The level of NO in ST36 group was
higher than that in NA group. The level of both ET-1 and NE was the highest in
control group, followed by NA group and ST36 group. It is concluded that EA at
ST36 could increase HBP possibly by increasing the blood flow velocity (BFV),
changing vascular activity, increasing the level of NO, and inhibiting the level
of ET-1 in liver tissue.
PMID- 25140189
TI - Caffeamide 36-13 Regulates the Antidiabetic and Hypolipidemic Signs of High-Fat
Fed Mice on Glucose Transporter 4, AMPK Phosphorylation, and Regulated Hepatic
Glucose Production.
AB - This study was to investigate the antidiabetic and antihyperlipidemic effects of
(E)-3-[3, 4-dihydroxyphenyl-1-(piperidin-1-yl)prop-2-en-1-one] (36-13) (TS), one
of caffeic acid amide derivatives, on high-fat (HF-) fed mice. The C57BL/6J mice
were randomly divided into the control (CON) group and the experimental group,
which was firstly fed a HF diet for 8 weeks. Then, the HF group was subdivided
into four groups and was given TS orally (including two doses) or rosiglitazone
(Rosi) or vehicle for 4 weeks. Blood, skeletal muscle, and tissues were examined
by measuring glycaemia and dyslipidemia-associated events. TS effectively
prevented HF diet-induced increases in the levels of blood glucose, triglyceride,
insulin, leptin, and free fatty acid (FFA) and weights of visceral fa; moreover,
adipocytes in the visceral depots showed a reduction in size. TS treatment
significantly increased the protein contents of glucose transporter 4 (GLUT4) in
skeletal muscle; TS also significantly enhanced Akt phosphorylation in liver,
whereas it reduced the expressions of phosphoenolpyruvate carboxykinase (PEPCK)
and glucose-6-phosphatase (G6Pase). Moreover, TS enhanced phosphorylation of AMP
activated protein kinase (phospho-AMPK) both in skeletal muscle and liver tissue.
Therefore, it is possible that the activation of AMPK by TS resulted in enhanced
glucose uptake in skeletal muscle, contrasting with diminished gluconeogenesis in
liver. TS exhibits hypolipidemic effect by decreasing the expressions of fatty
acid synthase (FAS). Thus, antidiabetic properties of TS occurred as a result of
decreased hepatic glucose production by PEPCK and G6Pase downregulation and
improved insulin sensitization. Thus, amelioration of diabetic and dyslipidemic
state by TS in HF-fed mice occurred by regulation of GLUT4, G6Pase, and FAS and
phosphorylation of AMPK.
PMID- 25140190
TI - Pharmacokinetics and tissue distribution study of chlorogenic Acid from lonicerae
japonicae flos following oral administrations in rats.
AB - Chlorogenic acid (ChA) is proposed as the major bioactive compounds of Lonicerae
Japonicae Flos (LJF). Forty-two Wistar rats were randomly divided into seven
groups to investigate the pharmacokinetics and tissue distribution of ChA, via
oral administration of LJF extract, using ibuprofen as internal standard,
employing a high performance liquid chromatography in conjunction with tandem
mass spectrometry. Analytes were extracted from plasma samples and tissue
homogenate by liquid-liquid extraction with acetonitrile, separated on a C 18
column by linear gradient elution, and detected by electrospray ionization mass
spectrometry in negative selected multiple reaction monitoring mode. Our results
successfully demonstrate that the method has satisfactory selectivity, linearity,
extraction recovery, matrix effect, precision, accuracy, and stability. Using
noncompartment model to study pharmacokinetics, profile revealed that ChA was
rapidly absorbed and eliminated. Tissue study indicated that the highest level
was observed in liver, followed by kidney, lung, heart, and spleen. In
conclusion, this method was suitable for the study on pharmacokinetics and tissue
distribution of ChA after oral administration.
PMID- 25140191
TI - Effects and mechanisms of resveratrol on the amelioration of oxidative stress and
hepatic steatosis in KKAy mice.
AB - BACKGROUND: The exact mechanism of the protective role of Resveratrol (Res) in
lipid metabolism and oxidative stress is not well elucidated. The present study
aimed to investigate the potential benefits and possible mechanisms of Res on the
amelioration of oxidative stress and hepatic steatosis in a KKAy mouse model.
METHODS: A total of 30 KKAy male mice were randomly divided into three groups: a
normal chow group, a low resveratrol group and a high resveratrol group. After a
12-wk study period, serum levels of TG, TC, LDL-C and HDL-C, the liver content of
TG and TC, ROS, GSH, GPx, SOD and MDA levels were measured. Ectopic lipid
deposition was observed in sectioned frozen liver tissues. The mRNA levels of
ATGL and HSL in the liver tissues were determined via real-time PCR. Furthermore,
the protein expression of p47phox, gp91phox, ATGL, HSL, Sirt1, AMPK and FOXO1
were analyzed using western blotting. RESULTS: Following Res supplementation,
serum levels of TG and MDA were decreased, while the HDL-C and SOD levels were
increased in KKAy mice. Furthermore, Res treatment increased GSH and GPx in liver
tissues, while it decreased ROS. In addition, Res significantly reduced hepatic
steatosis. After Res treatment, concentrations of p47phox (membrane) and gp91phox
proteins were reduced, while p-HSL, HSL and ATGL protein expression levels were
increased. Mechanistically, the levels of Sirt1, p-AMPK and p-FOXO1 expression in
the liver tissues were up-regulated following supplementation with Res, and FOXO1
protein was released from the nucleus into the cytoplasm. CONCLUSIONS: Res is
able to attenuate hepatic steatosis and lipid metabolic disorder and enhance the
antioxidant ability in KKAy mice, possibly by up-regulating Sirt1 expression and
the phosphorylation of AMPK.
PMID- 25140192
TI - Navigating diabetes-related immune epitope data: resources and tools provided by
the Immune Epitope Database (IEDB).
AB - BACKGROUND: The Immune Epitope Database (IEDB), originally focused on infectious
diseases, was recently expanded to allergy, transplantation and autoimmunity
diseases. Here we focus on diabetes, chosen as a prototype autoimmune disease. We
utilize a combined tutorial and meta-analysis format, which demonstrates how
common questions, related to diabetes epitopes can be answered. RESULTS: A total
of 409 references are captured in the IEDB describing >2,500 epitopes from
diabetes associated antigens. The vast majority of data were derived from GAD,
insulin, IA-2/PTPRN, IGRP, ZnT8, HSP, and ICA-1, and the experiments related to T
cell epitopes and MHC binding far outnumbers B cell assays. We illustrate how to
search by specific antigens, epitopes or host. Other examples include searching
for tetramers or epitopes restricted by specific alleles or assays of interest,
or searching based on the clinical status of the host. CONCLUSIONS: The inventory
of all published diabetes epitope data facilitates its access for the scientific
community. While the global collection of primary data from the literature
reflects potential investigational biases present in the literature, the flexible
search approach allows users to perform queries tailored to their preferences,
including or excluding data as appropriate. Moreover, the analysis highlights
knowledge gaps and identifies areas for future investigation.
PMID- 25140193
TI - Optimal treatment strategy for a tumor model under immune suppression.
AB - We propose a mathematical model describing tumor-immune interactions under immune
suppression. These days evidences indicate that the immune suppression related to
cancer contributes to its progression. The mathematical model for tumor-immune
interactions would provide a new methodology for more sophisticated treatment
options of cancer. To do this we have developed a system of 11 ordinary
differential equations including the movement, interaction, and activation of NK
cells, CD8(+)T-cells, CD4(+)T cells, regulatory T cells, and dendritic cells
under the presence of tumor and cytokines and the immune interactions. In
addition, we apply two control therapies, immunotherapy and chemotherapy to the
model in order to control growth of tumor. Using optimal control theory and
numerical simulations, we obtain appropriate treatment strategies according to
the ratio of the cost for two therapies, which suggest an optimal timing of each
administration for the two types of models, without and with immunosuppressive
effects. These results mean that the immune suppression can have an influence on
treatment strategies for cancer.
PMID- 25140194
TI - A biological hierarchical model based underwater moving object detection.
AB - Underwater moving object detection is the key for many underwater computer vision
tasks, such as object recognizing, locating, and tracking. Considering the super
ability in visual sensing of the underwater habitats, the visual mechanism of
aquatic animals is generally regarded as the cue for establishing bionic models
which are more adaptive to the underwater environments. However, the low accuracy
rate and the absence of the prior knowledge learning limit their adaptation in
underwater applications. Aiming to solve the problems originated from the
inhomogeneous lumination and the unstable background, the mechanism of the visual
information sensing and processing pattern from the eye of frogs are imitated to
produce a hierarchical background model for detecting underwater objects.
Firstly, the image is segmented into several subblocks. The intensity information
is extracted for establishing background model which could roughly identify the
object and the background regions. The texture feature of each pixel in the rough
object region is further analyzed to generate the object contour precisely.
Experimental results demonstrate that the proposed method gives a better
performance. Compared to the traditional Gaussian background model, the
completeness of the object detection is 97.92% with only 0.94% of the background
region that is included in the detection results.
PMID- 25140195
TI - Effects of first-time overnight CPAP therapy for increasing the complexity of the
patient's physiological system.
AB - Studies regarding the effects of short-term continuous positive airway pressure
(CPAP) therapy are not sufficient. A total of 35 patients with moderate to severe
untreated OSA were divided into 2 groups. Group 1 comprised 22 patients who
underwent polysomnography (PSG) for one night, and Group 2 comprised 13 patients
who received PSG combined with CPAP therapy. To evaluate the influence of
receiving CPAP therapy for one night, we measured 5 min wrist pulse signals
before and after the experiment to assess heart rate variability, as well as
novel short time multiscale entropy (sMSE) indicator that examines complexity in
physiological signals. The results show that the participants in Group 1
exhibited significant changes in normalized low-frequency power/normalized high
frequency power (nLF/nHF) (0.72 +/- 0.09 versus 1.11 +/- 0.11, P = 0.006) values
before and after the PSG study. By contrast, the participants in Group 2 showed
no significant changes in the 3 indicators. Regarding the sMSE indicator, Group 2
patients exhibited significant increases in the sMSE. CPAP therapy administered
for one night can reduce the sympathovagal imbalance in patients with moderate to
severe untreated OSA and increase the complexity of the patient's physiological
system, thereby reflecting their overall improved health.
PMID- 25140196
TI - Isolated dissection of the superior mesenteric artery treated using open
emergency surgery.
AB - BACKGROUND: Isolated dissection of the superior mesenteric artery (IDSMA) remains
a rare diagnosis. However, new diagnostic means such as computed tomography makes
it possible to detect even asymptomatic patients. If patients present symptomatic
on admission, the risk of bowel infarction makes immediate therapy necessary.
Today, endovascular techniques are often successfully used; however, open surgery
remains important for special indications. In this paper, we present two cases
with IDSMA and show why open surgical repair is still important in current
treatment concepts. METHODS: Two cases with ISDMA that presented in our
department from January 1, 2014 to June 1, 2014 are described. Data collection
was performed retrospectively. Additionally, a review of articles which reported
small cases series on patients with IDSMA within the past five years is provided.
RESULTS: Both patients underwent open surgical repair following interdisciplinary
consultation. Both patients were transferred to the intensive care unit after
surgical repair and needed bowel rest, nasogastric suction and intravenous fluid
therapy. CT scans were performed within the first week after operation. Platelet
aggregation inhibitors were used in both cases as postoperative medication. Both
patients survived and are able to participate in everyday activities. CONCLUSION:
Open surgical repair remains important in cases of anatomic variants of visceral
arteries and suspected bowel infarction. Therefore, it is important that
knowledge about open surgical techniques still be taught and trained.
PMID- 25140197
TI - Decitabine and SAHA-induced apoptosis is accompanied by survivin downregulation
and potentiated by ATRA in p53-deficient cells.
AB - While p53-dependent apoptosis is triggered by combination of methyltransferase
inhibitor decitabine (DAC) and histone deacetylase inhibitor suberoylanilide
hydroxamic acid (SAHA) in leukemic cell line CML-T1, reactive oxygen species
(ROS) generation as well as survivin and Bcl-2 deregulation participated in DAC +
SAHA-induced apoptosis in p53-deficient HL-60 cell line. Moreover, decrease of
survivin expression level is accompanied by its delocalization from centromere
related position in mitotic cells suggesting that both antiapoptotic and cell
cycle regulation roles of survivin are affected by DAC + SAHA action. Addition of
subtoxic concentration of all-trans-retinoic acid (ATRA) increases the efficiency
of DAC + SAHA combination on viability, apoptosis induction, and ROS generation
in HL-60 cells but has no effect in CML-T1 cell line. Peripheral blood
lymphocytes from healthy donors showed no damage induced by DAC + SAHA + ATRA
combination. Therefore, combination of ATRA with DAC and SAHA represents
promising tool for therapy of leukemic disease with nonfunctional p53
signalization.
PMID- 25140199
TI - Production and characterization of polyclonal antibody against a synthetic
peptide from beta-actin protein.
AB - OBJECTIVES: Antibodies against actin, as one of the most widely studied
structural and multifunctional housekeeping proteins in eukaryotic cells, are
used as internal loading controls in western blot analyses. The aim of this study
was to produce polyclonal antibody against a synthetic peptide derived from N
terminal region of beta-actin protein to be used as a protein loading control in
western blot and other assay systems. MATERIALS AND METHODS: A synthetic peptide
derived from beta-actin protein was designed and conjugated to Keyhole limpet
hemocyanin (KLH) and used to immunize a white New Zealand rabbit. The antibody
was purified from serum by affinity chromatography column. The purity of the
antibody was determined by SDS-PAGE and its ability to recognize the immunizing
peptide was measured by ELISA. The reactivity of the antibody with beta-actin
protein in a panel of different cell lysates was then evaluated by western blot.
In addition, the reactivity of the antibody with the corresponding protein was
also evaluated by Immunocytochemistry and Immunohistochemistry in different
samples. RESULTS: The antibody could recognize the immunizing peptide in ELISA.
It could also recognize beta-actin protein in western blot as well as in
immunocytochemistry and immunohistochemistry. CONCLUSION: Our data suggest that
this antibody may be used as an internal control in western blot analyses as well
as in other immunological applications such as ELISA, immunocytochemistry and
immunohistochemistry.
PMID- 25140200
TI - Comparison of the genetic convergence between mycobacterium strains by three RFLP
based methods in central province of Iran.
AB - OBJECTIVES: The utilization of molecular techniques in the epidemiology of
tuberculosis have provided an opportunity for using effective markers to trace
the transmission of the disease. The purpose of this study was to compare the
genetic patterns of Mycobacterium tuberculosis by three methods of RFLP
technique. MATERIALS AND METHODS: In a cross-sectional and prospective study, 95
strains of M. tuberculosis isolates were selected for DNA fingerprinting.
Extraction of DNA from Mycobacterium strains and DNA fingerprinting with IS-6110,
PGRS and DR probe were performed by standard protocols. RESULTS: Overall, the
diversity of RFLP among 95 tuberculosis patients were 48, 50 and 45 on the basis
of IS6110, PGRS and DR patterns, respectively. Twenty of these patterns (21.1%)
with IS6110-RFLP, twenty-two (23.2%) with PGRS-RFLP and seventeen (17.9%) with DR
RFLP occurred with unique RFLP patterns, whereas the remaining 28 patterns were
communal. The risk factors of clustering among tuberculosis patients were age <
45 years, new cases, degree of sputum smear >= 2+, and close contact. CONCLUSION:
Our study demonstrated that IS6110-RFLP, PGRS-RFLP and DR-RFLP genotyping could
roughly identify similar proportions of clustered (secondary) cases as well as
the same risk factors for clustering.
PMID- 25140201
TI - The effects of cyclooxygenase inhibitors on the gastric emptying and small
intestine transit in the male rats following traumatic brain injury.
AB - OBJECTIVES: This study was carried out to investigate the effects of COX-2
selective inhibitor (Celecoxib) or non-selective COX inhibitor (Ibuprofen) on
gastrointestinal motility. MATERIALS AND METHODS: THE RATS WERE RANDOMLY DIVIDED
INTO FIVE GROUPS INCLUDING: intact, sham, traumatic brain injury (TBI) group
(intact rats under TBI), Celecoxib group (10 mg/kg), Ibuprofen group (10 mg/kg).
Rats of the treatment groups received gavages at 1 hr before the TBI induction.
The TBI was moderate and diffused using the Marmarou method. The gastric emptying
and small intestine transit were measured by phenol red method. RESULTS: The
gastric emptying didn't change following TBI induction compared to intact group.
The consumption of ibuprofen or celecoxib didn't have any effect on gastric
emptying compared to sham group. TBI induction didn't have any effect on the
intestinal transit. Also, there was no significant difference between ibuprofen
or celecoxib consumption vs. sham group (P>0.05). CONCLUSION: The COX-2 selective
inhibitor (celecoxib) or non-selective COX inhibitor (ibuprofen) have no effects
on gastric or small bowel transit. Further work is necessary to investigate the
effects of non-selective COX inhibitors and their impact on gastrointestinal
motility disorders.
PMID- 25140202
TI - The effects of nano-silver and garlic administration during pregnancy on neuron
apoptosis in rat offspring hippocampus.
AB - OBJECTIVES: The aim of this study was to investigate the effects of nano-silver
and garlic administration during pregnancy on neuron apoptosis in rat offspring
hippocampus. MATERIALS AND METHODS: FIFTY PREGNANT WISTAR RATS WERE RANDOMLY
DIVIDED INTO FIVE GROUPS: 1- nano-silver (N.S) group; 30 mg/kg of N.S treated via
gavage. 2- Control (C) group, administrated with distilled water via gavage. 3-
N.S and garlic (N.S+G) group; N.S (30 mg/kg) and garlic juice (1 ml/100 g)
treated via gavage simultaneously. 4- Garlic group (G); garlic juice (1 ml/100 g)
administrated via gavage, 5- normal (N) without any intervention. All the
interventions were done during pregnancy (21 days). Finally, the brains of rat
offspring were removed to use for nano-silver level measurement and TUNEL
staining. The mean of TUNEL positive cell numbers per unit area (NA) in different
regions of hippocampus were compared in all animal groups. RESULTS: The results
revealed a significant increase of hippocampus nano-silver level in N.S and N.S+G
groups comparing to N group (P<0.05) and a significant decrease in nano-silver
level in N.S+G group comparing to N.S group (P<0.01). The number of TUNEL
positive cells in the CA1, CA3, and DG fields of rat offspring hippocampus
increased in N.S and N.S+G groups comparing to other ones, and also reduced
significantly in N.S+G group comparing to N.S group ((Y) P< 0.01). CONCLUSION:
Our results showed that co-administration of nano-silver and garlic during
pregnancy may lead to reduce nano-silver induced apoptotic cells in their
offspring hippocampus.
PMID- 25140198
TI - The protective role of antioxidants in the defence against ROS/RNS-mediated
environmental pollution.
AB - Overproduction of reactive oxygen and nitrogen species can result from exposure
to environmental pollutants, such as ionising and nonionising radiation,
ultraviolet radiation, elevated concentrations of ozone, nitrogen oxides, sulphur
dioxide, cigarette smoke, asbestos, particulate matter, pesticides, dioxins and
furans, polycyclic aromatic hydrocarbons, and many other compounds present in the
environment. It appears that increased oxidative/nitrosative stress is often
neglected mechanism by which environmental pollutants affect human health.
Oxidation of and oxidative damage to cellular components and biomolecules have
been suggested to be involved in the aetiology of several chronic diseases,
including cancer, cardiovascular disease, cataracts, age-related macular
degeneration, and aging. Several studies have demonstrated that the human body
can alleviate oxidative stress using exogenous antioxidants. However, not all
dietary antioxidant supplements display protective effects, for example, beta
carotene for lung cancer prevention in smokers or tocopherols for photooxidative
stress. In this review, we explore the increases in oxidative stress caused by
exposure to environmental pollutants and the protective effects of antioxidants.
PMID- 25140203
TI - The effects of tramadol on norepinephrine and MHPG releasing in locus coeruleus
in formalin test in rats: a brain stereotaxic study.
AB - OBJECTIVES: The relationship between tramadol, as an antinociceptive drug, and
locus coeruleus (LC), the main noradrenergic nucleus of the brain that affects
regulation and modulation of pain through descending noradrenergic pathways was
investigated. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into
four groups of 10 rats. The rats were fixed in stereotaxic instrument and then a
probe was inserted into LC. Pain was induced by subcutaneous injection of 50 MUl
of 2.5% formalin 40 minutes after initiation of microdialysis in right hind paw,
and nociceptive pain scores were calculated every 5 minutes. Subsequently
noradrenaline (NA) and its metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG),
were collected and measured by microdialysis of locus coeruleus in freely moving
rats every 15 minutes during formalin injection. RESULTS: Nociceptive pain scores
observed in formalin test had the highest nociceptive sensation 5 minutes after
injection. Significant rises in concentrations of NA and MHPG, in samples taken
between 30 and 45 min after initiation of the locus coeruleus microdialysis,
coincided with the peak of the pain after injection of formalin. CONCLUSION:
According to concurrency of the highest nociceptive sensation and peak of NE and
MHPG concentrations, tramadol can indirectly affect the LC by blocking the pain
signals from different parts of the brain such as periaqueductal gray mater,
central nucleus of amygdale or the spinal cord.
PMID- 25140204
TI - Enzyme inhibitory and radical scavenging effects of some antidiabetic plants of
Turkey.
AB - OBJECTIVES: Ethnopharmacological field surveys demonstrated that many plants,
such as Gentiana olivieri, Helichrysum graveolens, Helichrysum plicatum ssp.
plicatum, Juniperus oxycedrus ssp. oxycedrus, Juniperus communis var. saxatilis,
Viscum album (ssp. album, ssp. austriacum), are used as traditional medicine for
diabetes in different regions of Anatolia. The present study was designed to
evaluate the in vitro antidiabetic effects of some selected plants, tested in
animal models recently. MATERIALS AND METHODS: alpha-glucosidase and alpha
amylase enzyme inhibitory effects of the plant extracts were investigated and
Acarbose was used as a reference drug. Additionally, radical scavenging
capacities were determined using 2,2'-azino-bis(3-ethylbenzothiazoline-6
sulphonic acid) ABTS radical cation scavenging assay and total phenolic content
of the extracts were evaluated using Folin Ciocalteu method. RESULTS: H.
graveolens ethanol extract exhibited the highest inhibitory activity (55.7 % +/-
2.2) on alpha-amylase enzyme. Additionally, J. oxycedrus hydro-alcoholic leaf
extract had potent alpha-amylase inhibitory effect, while the hydro-alcoholic
extract of J. communis fruit showed the highest alpha-glucosidase inhibitory
activity (IC50: 4.4 MUg/ml). CONCLUSION: Results indicated that, antidiabetic
effect of hydro-alcoholic extracts of H. graveolens capitulums, J. communis fruit
and J. oxycedrus leaf might arise from inhibition of digestive enzymes.
PMID- 25140205
TI - Gender difference in motor impairments induced by chronic administration of
vinblastine.
AB - OBJECTIVES: Neurotoxicity of anticancer drugs complicates treatment of cancer
patients. Vinblastine (VBL) is reported to induce motor and cognitive impairments
in patients receiving chronic low-dose regimen. MATERIALS AND METHODS: The
effects of VBL treatment on motor, learning and memory functions of male and
female Wistar rats were studied by behavioral related tests. Animals were given
chronic intraperitoneal injections of VBL (0.2 mg/kg/week for 5 weeks) from
postnatal day 23 to 52. Motor function was evaluated using grasping test and
balancing was evaluated by the rotarod. Spatial learning and memory and anxiety
like behavior were determined using Morris water maze (MWM) task and open field
test, respectively. RESULTS: Administration of VBL caused severe damage to motor
and balance function of male rats in comparison to female rats treated with VBL
and rats treated with saline. Memory and locomotion were affected in both male
and female rats compared with saline treated rats, while a sex difference was
also observed in these parameters; male rats showed more impairment compared with
female ones. Both male and female rats showed cognitive impairments in MWM task
and no sex differences were observed in these functions. CONCLUSION: Results
revealed that VBL is a potent neurotoxic agent and despite the profound effect of
VBL on motor and cognitive functions, it seems that male rats are more
susceptible to motor deficits induced by VBL.
PMID- 25140206
TI - Frequencies of two functionally significant SNPs and their haplotypes of organic
anion transporting polypeptide 1B1 SLCO1B1 gene in six ethnic groups of Pakistani
population.
AB - OBJECTIVES: Organic anion transporter polypeptide 1B1 (OATP1B1) encoded by solute
carrier organic transporter 1B1 (SLCO1B1) gene; a transporter involved in the
uptake of drugs and endogenous compounds is present in hepatocyte sinusoidal
membrane. Aim of this study was to investigate the frequencies of functionally
significant SNPs (388A>G and 521T>C) and their haplotypes in 6 ethnic groups of
Pakistani population through the development of rapid and efficient Tetra
amplification refractory mutation system (T. ARMS) genotyping assay. MATERIALS
AND METHODS: Frequencies of alleles, genotype, and haplotypes of two functionally
significant Single nucleotide polymorphism in 180 healthy Pakistani subjects and
distributions in six ethnic groups by using a single step T. ARMS genotyping
assay. RESULTS: The allelic frequency for 388A>G SNP was 50% in total Pakistani
population with Single nucleotide polymorphism distributions of 9.7%, 15.1%,
19.4%, 16.1%, 18.3%, and 21.5% in Punjabi, Sindhi, Balouchi, Pathan, Kashmiri and
Hazara/Baltistan groups respectively; and for 521T>C SNP it was 23.9% in total
Pakistani population with distributions of 11.1%, 8.9%, 15.6%, 11.1%, 31.1% and
22.2% in Punjabi, Sindhi, Balouchi, Pathan, Kashmiri, and Hazara/Baltistan
groups. Both functionally significant SNPs occurred in four major haplotypes with
a frequency of 35.5% for 388A/521T (*1A), 40.5% for 388G/521T (*1B), 14.4% for
388A/521C (*5), and 9.4% for 388G/521C (*15) with varying distributions among six
ethnic groups. CONCLUSION: The 388A>G and 521T>C genotypes and corresponding
haplotypes are present at varying frequencies in various ethnic groups of
Pakistani population. Pharmacokinetic and pharmacodynamic profiling is needed to
assess and characterize the effects of these haplotypes in our population.
PMID- 25140207
TI - Pantoprazole, a proton pump inhibitor, increases orthodontic tooth movement in
rats.
AB - OBJECTIVES: Pantoprazole, is a proton pump inhibitor (PPI) prescribed for the
treatment of upper gastrointestinal disorders, which in high doses has been
suggested to decrease calcium absorption leading to hypocalcaemia and therefore
osteoporosis. The aim of this study was to assess whether pantoprazol, could
alter the rate of orthodontic tooth movement (OTM) in rats. MATERIALS AND
METHODS: A time course study was established using 72 rats which were divided
into six groups of 12 samples each (four: vehicle; eight: pantoprazole +
vehicle). Pantoprazole at a dose of 200 mg/kg suspended in carboxymethyl
cellulose (0.25 percent) was administered by a gastric tube. The upper incisors
and first molars were ligated by a 5 mm nickel-titanium closed-coil spring to
deliver an initial force of 60 g. Animals were euthanized two weeks after
orthodontic treatment followed by assessment of tooth movement and
histomorphometric evaluation of the detached maxillae. Lateral skull radiographs
were obtained once a week, starting from the first day to the 6(th) week of the
study. OTM and bone density data were analyzed using independent sample t-test
and repeated measures ANOVA. RESULTS: No significant changes in OTM measurements
and optical density were observed in vehicle-receiving animals during the study
(P=0.994). OTM was significantly increased after six weeks pantoprazole therapy
which continued until the 7(th) week of the experiment (P=0.007). Optical density
significantly increased in the pantoprazole-treated rats after six weeks.
CONCLUSION: Long term PPI therapy at high doses could lead to osteoporosis and
enhanced OTM.
PMID- 25140208
TI - Mild hypothermia reduces expression of Fas/FasL and MMP-3 after cerebral ischemia
reperfusion in rats.
AB - OBJECTIVES: To investigate the effects of local mild hypothermia on the
expression of Fas, FasL and MMP-3 after cerebral ischemia-reperfusion in rats.
MATERIALS AND METHODS: Male Wistar rats were divided into sham-operated group
(Sham), normothermia group (NT), and hypothermia group (HT). MCAO/R model was
established by Longa's method, and reperfusion was allowed after 2 hr occlusion.
Mild hypothermia (33+/-0.5 degrees C) for 6 hr was initiated at the start of
reperfusion. Immunohistochemistry was performed to determine expression Fas,
FasL, and MMP-3. RESULTS: Infarct volume was reduced in the hypothermia group
(18.43+/-4.23%) compared with the normothermia group (24.76+/-5.76%) (P<0.05). In
mild hypothermia group, numbers of Fas-positive and MMP-3 positive cells were
significantly less than those of normothermia group (P<0.05). Neurological
functional scores of mild hypothermia were significantly improved (P<0.05).
CONCLUSION: Mild hypothermia decreases infarct volume after cerebral ischemia
reperfusion, reduces Fas and MMP-3 expression, but increases FasL in cerebral
ischemia-reperfusion rats.
PMID- 25140209
TI - Antioxidant effects of proanthocyanidin from grape seed on hepatic tissue injury
in diabetic rats.
AB - OBJECTIVES: Diabetes plays an important role in the induction of the liver
injury. Grape seed proanthocyanidin (GSP) have a wide range of medicinal
properties against oxidative stress. In this study we evaluated antioxidant
effects of GSP on liver in streptozotocin-induced diabetic rats. MATERIALS AND
METHODS: Thirty male Sprague-Dawley rats were divided into three groups: control,
untreated diabetic and diabetic rats treated with GSP. Diabetes was induced in
rats by intraperitoneal injection of streptozotocin (50 mg/kg). GSP were
administered via oral gavage (200 mg/kg) for 4 weeks. RESULTS: GSP produced
significant hepatoprotective effects by decreasing activities of serum
aminotransferases and alkaline phosphatase, and decreasing liver malondialdehyde
and bilirubin (P<0.05) levels. It increased liver superoxide dismutase, catalase
and glutathione peroxidase activities and albumin level (P<0.05). Administration
of GSP significantly ameliorated structural changes induced in liver of diabetic
rats. CONCLUSION: GSP have protective effects against hepatic tissue injury due
to antioxidant properties.
PMID- 25140210
TI - Evaluation of alpha- amylase inhibition by Urtica dioica and Juglans regia
extracts.
AB - OBJECTIVES: One strategy for the treatment of diabetes is inhibition of
pancreatic alpha- amylase. Plants contains different chemical constituents with
potential for inhibition of alpha-amylase and hence maybe used as therapeutic.
MATERIALS AND METHODS: Urtica dioica and Juglans regia Linn were tested for alpha
amylase inhibition. Different concentrations of leaf aqueous extracts were
incubated with enzyme substrate solution and the activity of enzyme was measured.
For determination of the type of inhibition, Dixon plot was depicted. Acarbose
was used as the standard inhibitor. RESULTS: Both plant extracts showed time and
concentration dependent inhibition of alpha-amylase. 60% inhibition was seen with
2 mg/ml of U. dioica and 0.4 mg/ml of J. regia aqueous extract. Dixon plots
revealed the type of alpha-amylase inhibition by these two extracts as
competitive inhibition. CONCLUSION: Determination of the type of alpha-amylase
inhibition by these plant extracts could provide by successful use of plant
chemicals as drug targets.
PMID- 25140211
TI - Potential effect of opium consumption on controlling diabetes and some
cardiovascular risk factors in diabetic patients.
AB - BACKGROUND: Due to this belief that opium may have beneficial effects on diabetes
or cardiovascular risk factors, the present study aimed to assess the potential
and possible effects of opium consumption on diabetes control and some
cardiovascular risk factors in diabetic patients. METHODS: This study enrolled
374 diabetic subjects from diabetes care centers in Kerman, Iran, including opium
user group (n = 179) and a non-opium user group (n = 195). The data were
collected through a questionnaire completed by interviewing, physical examination
and laboratory assessment. FINDINGS: Opium did not show any statistically
significant effect on blood glucose, glycated hemoglobin (HbA1C), fasting blood
sugar (FBS), low-density lipoprotein (LDL) and diastolic blood pressure. However,
systolic blood pressure (SBP) and prevalence of high SBP were significantly
higher in opium user group (P < 0.050). In addition, lower serum high-density
lipoprotein (HDL) and frequency of lower HDL was significantly higher in opium
user group (P < 0.001). CONCLUSION: According to this study, opium does not seem
to have beneficial effects on diabetes control or cardiovascular risk factors.
Therefore, it would not be advisable to consume opium as an anti-diabetes or
cardioprotective agent.
PMID- 25140212
TI - Effect of opium addiction on aspirin resistance in stable angina pectoris.
AB - BACKGROUND: The rate of cardiovascular diseases in developing countries is
approximately 60% and it is still has an increasing trend. The clinical
effectiveness of aspirin in preventing cardiovascular events has been well
proven. Although aspirin is an effective and inexpensive drug, its consumption is
not equally beneficial for all patients. Many factors can be affective on the
efficacy of antiplatelet drugs such as aspirin. METHODS: This study was carried
out on 260 patients who had stable angina pectoris and coronary artery disease
was approved by coronary angiography. Based on opium addiction, the patients were
divided into two groups. Opium addiction was diagnosed base on Diagnostic and
Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. The mid
stream morning urinary sample were collected for measuring the urinary 11
dehydroxy thromboxane B2 level (UTXB2). Urinary level of UTXB2 was considered as
an aspirin resistance index. FINDINGS: The mean age of patients was 57.3 +/- 8.9;
and 44.6% of them were females. The aspirin resistance rate was 41.5%.
Significant difference in aspirin resistance was observed between the opium
addicts and non-addicts. (51.5% vs. 31.5%) (P = 0.001). The effects of
confounding variables such as diabetes, hypertension, and hyperlipidemia were
eliminated by regression logistic multivariable analysis. CONCLUSION: The
prevalence of aspirin resistance in patients with stable angina pectoris was
41.5%. The prevalence of aspirin resistance in patients with stable angina
pectoris who had opium addiction was significantly higher them non-addicts.
PMID- 25140213
TI - Challenges in the Area of Training and Prevention at the HIV Triangulation
Clinic, Kerman, Iran.
AB - BACKGROUND: Since 2000, Iran has been delivering training and treatment services,
including methadone therapy, to human immunodeficiency virus (HIV) positive
patients through triangular clinics. This study aims to evaluate the
effectiveness of these activities at the HIV Triangulation Centre in the city of
Kerman, Iran, through clients' views. METHODS: Participants were recruited using
a convenience sample and assessed through in-depth interviews, and observations.
Data were analyzed using a thematic analysis, matrix based method. FINDINGS: The
results found problems in training and counseling which was described by the
staff to be due to the effects of the economic difficulties of the clients, not
being of the same sex as the consultant, and lack of utilization of a variety of
training methods by the clients. Furthermore, the absorption of clients was
perceived as being affected by the appearance of the center, gossip around the
center, limited working hours, and interpersonal relations between clients and
staff. The clients also criticized the building of the center as it failed to
maintain anonymity of the patients. The need for supplementary services, such as
dentistry, was perceived by many clients. CONCLUSION: The application of
appropriate strategies such as providing adequate training and removing the
obstacles of absorption should be taken into account to increase the utility and
coverage of the triangular clinic. These interventions could be a range of
activities, such as relocating the center to a more decent place and encouraging
the staff to appear in a professional white coat to help gain the trust of
clients.
PMID- 25140214
TI - Drug Use among Residents of Juvenile Correctional Center in Kerman, Iran, and its
Relationship with Personality Dimensions and Self-concept.
AB - BACKGROUND: Identifying the status of substance misuse and its psychosocial
correlates among residents of juvenile correctional centers, as a high risk
group, could potentially illuminate the roadmap to prevention of drug use in this
group. METHODS: In this cross-sectional study, 93 individuals aged 13 to 18 were
enrolled. A self-administered questionnaire was completed and dropped in a sealed
box. It consisted of 4 parts of Piers-Harris Children's Self-Concept Scale, NEO
Personality Inventory, drug use questions, and demographic variables. All
questionnaires were well adapted in the Persian language. MANOVA was used to
compare the subscale scores between the drug users and nonusers. FINDINGS: All
respondents were male and 40% were illiterate. More than 40% had drug dependent
fathers. Use of cigarette, opium, and alcohol in the previous 30 days was
reported by 31.9, 52.2, and 15.9% of respondents, respectively. In this
population, the score of 3 of the 5 personality factors (i.e., neuroticism,
extraversion, and openness) were higher than in the general population (P <
0.001). More than 88% of subjects had negative self-concept. Both the scores of
personality and self-concept showed no significant difference based on the status
of drug use. CONCLUSION: Prevalence of lifetime and last-month drug use was found
to be high. Regarding the profiles of personality and self-concept, more
comprehensive evidence-based interventions are needed for improvement of their
mental health.
PMID- 25140215
TI - The Prevalence of Musculoskeletal Pain and Forward Head Posture among Heroin
Users during their Withdrawal with Methadone.
AB - BACKGROUND: Heroin is an extremely addictive narcotic drug derived from morphine.
Its continued use requires increased amounts of the drug to achieve the same
effect, resulting in tolerance and addiction. This study was done in order to
determine the prevalence of musculoskeletal pain and forward head posture among
heroin users during their withdrawal. METHODS: This research was a cross
sectional study that was done on 90 heroin users (83 males, 7 females) aged
between 20 to 40 years (32.5 +/- 3.81) during their withdrawal in Shiraz, Iran.
They were selected by simple randomized sampling. Data were collected by a form
regarding age, sex, the duration of heroin use, and musculoskeletal pain. Pain
was measured by VAS (visual analog scale) and forward head posture was evaluated
by plumb line. Pearson correlation technique and chi-square were used for
analyzing the data. FINDINGS: The results revealed that the majority of heroin
users suffered from musculoskeletal pain during their withdrawal. At the end of
withdrawal 53.4% had severe pain, 38.8% had moderate pain, and 7.8% of them had
mild pain. Pain in the lower extremities and low back was more common than the
upper extremities. The intensity of pain before withdrawal was mild, during
withdrawal was moderate, and at the end was sever, but there was no significant
correlation between them. The results also showed 43.3% of subjects had normal
posture and 56.7% had forward posture. CONCLUSION: According to the results, the
intensity of pain increased during the withdrawal period; therefore, more
attention must be paid to this complication in heroin users for better evaluation
and a successful withdrawal.
PMID- 25140216
TI - Selection of Variables that Influence Drug Injection in Prison: Comparison of
Methods with Multiple Imputed Data Sets.
AB - BACKGROUND: Prisoners, compared to the general population, are at greater risk of
infection. Drug injection is the main route of human immunodeficiency virus
y(HIV) transmission, in particular in Iran. What would be of interest is to
determine variables that govern drug injection among prisoners. However, one of
the issues that challenge model building is incomplete national data sets. In
this paper, we addressed the process of model development when missing data
exist. METHODS: Complete data on 2720 prisoners was available. A logistic
regression model was fitted and served as gold standard. We then randomly omitted
20%, and 50% of data. Missing date were imputed 10 times, applying multiple
imputation by chained equations (MICE). Rubin's rule (RR) was applied to select
candidate variables and to combine the results across imputed data sets. In S1,
S2, and S3 methods, variables retained significant in one, five, and ten imputed
data sets and were candidate for the multifactorial model. Two weighting
approaches were also applied. FINDINGS: Age of onset of drug use, recent use of
drug before imprisonment, being single, and length of imprisonment were
significantly associated with drug injection among prisoners. All variable
selection schemes were able to detect significance of these variables.
CONCLUSION: We have seen that the performances of easier variable selection
methods were comparable with RR. This indicates that the screening step can be
used to select candidate variables for the multifactorial model.
PMID- 25140217
TI - The Relationship between Perfectionism and Coping Strategies in Drug-dependent
Men.
AB - BACKGROUND: The aim of this study was to examine the relationship between
perfectionism and coping strategies in drug-dependent men. This study is a
descriptive correlational study. METHODS: The statistical population of this
study consisted of all drug-dependent men (n = 6237) in years 2010-2011, who were
admitted to all self-referral rehabs in Kerman, Iran. From this statistical
population, 361 individuals were selected using randomized cluster sampling. The
measurement tools applied in this study were positive and negative perfectionism
questionnaires (Terry-Short et al) and coping responses (Blinger and Moose).
FINDINGS: The data was analyzed using statistical methods, Pearson Coefficient
Correlation and multivariable regression inferential statistics. The results
showed that there is a significant correlation between positive and negative
perfectionism and problem-focused and emotion-focused coping strategies (P <=
0.010). CONCLUSION: The results of the current study show that positive and
negative perfectionism predicts problem-focused and emotion-focused coping
strategies for drug-dependent men.
PMID- 25140218
TI - Single and repeated ultra-rapid detoxification prevents cognitive impairment in
morphine addicted rats: a privilege for single detoxification.
AB - BACKGROUND: Opioids have been shown to affect learning and memory processes.
Different protocols of morphine withdrawal can substantially vary in their
success to prevent opioid induced impairments of cognitive performance. In the
present study, we report the effects of single and repetitive ultra-rapid
detoxification (URD) on spatial learning and memory in morphine addicted rats.
METHODS: Morphine (10 mg/kg) was intraperitoneally (IP) injected in male rats
once a day over one week and after which they were detoxified with naloxone
administration under anesthesia. For the repetitive procedure, a second one week
morphine treatment with a second subsequent detoxification was performed. Control
groups received an equivalent volume of saline injections. Spatial learning and
memory was evaluated using the Morris water maze (MWM) task. FINDINGS: Both
protocols of morphine administration resulted in a severe spatial memory
impairment that could be significantly prevented by both single and repetitive
URD. However, memory abilities in animals treated with repetitive URD were still
significantly lower than in animals of the corresponding control group.
Alterations in motor activity or sensory-motor coordination between morphine
treated and control animals could be ruled out by comparing swimming speed and
visible platform performances that were not different between groups. Thus, URD
and, specifically single URD, can prevent the spatial memory impairments in
addicted rats. CONCLUSION: As opioid addiction is an extending and serious
concern in many societies, these findings may have clinical values and
therapeutic implications for patients who experience multiple opioid relapses.
PMID- 25140219
TI - Ginger (zingiber officinale roscoe) prevents morphine-induced addictive behaviors
in conditioned place preference test in rats.
AB - BACKGROUND: Consumption of chronic morphine induces neuro-inflammation and
addictive seeking behavior. Ginger (Zingiber Officinale Roscoe), a well-known
spice plant, has been used traditionally in the treatment of a wide variety of
ailments. It has been shown that ginger has anti-inflammatory, anti-oxidative and
antinociceptive properties. However, its influences on morphine-induced addictive
behaviors have not yet been clarified. The aim of the present study was the
inhibition of exploratory behavior of morphine addiction in the conditioned place
preference test in male desert rats through ginger. METHODS: For conditioning to
the morphine, the male Wistar rats received morphine (12 mg/kg intraperitoneally
or i.p.) for 6 consecutive days and treatment groups were given different doses
of ginger (25, 50 and 100 mg/kg intragastrically or i.g.) 30 min before morphine
injection. For investigating addictive seeking behavior, conditioned place
preference test (CPP) was used. FINDINGS: Our result demonstrated that injection
of morphine for 6 days induces dependency to morphine and creates addictive
seeking behavior and ginger (100 mg/kg) could decrease time spend in conditioning
box (addictive seeking behavior). CONCLUSION: The data indicated that ginger
extract has a potential anti-addictive property against chronic usage of
morphine.
PMID- 25140220
TI - Attitudes, Practices and Perceived Barriers in Smoking Cessation among Dentists
of Udaipur City, Rajasthan, India.
AB - BACKGROUND: Tobacco is one of the most important causes of morbidity and
mortality. Tobacco toll in India has one-fifth of all worldwide death attributed
to tobacco. There are 700000 deaths per year due to smoking and 800000-900000 per
year to all forms of tobacco use of exposure in India. The role of dentist in
supporting their patients to quit smoking has been recognized. The present study
was conducted to know the attitudes, practices and barriers in tobacco cessation
among dentists of Udaipur city (Rajasthan, India). METHODS: A pretested, close
ended, self-administered, coded questionnaire was distributed among all the 262
dental health practitioners and the teaching staff. Out of 262 questionnaires
distributed among the dentist, 151 dentists filled out and returned the
questionnaire. FINDINGS: The majority of the dentists (98.7%) agreed that it was
their responsibility to provide smoking cessation counseling. 54.3% of dentists
agreed that such discussions were too time consuming. 37.1% thought they lacked
knowledge regarding this subject. 35.8% feared to an extent about patient leaving
their clinic if counseled much. CONCLUSION: In general, the dentists had a
favorable attitude in tobacco cessation counseling for the patients; however, the
lack of time and knowledge and to an extent, a fear that the patients would leave
their clinic, was the main identified barriers.
PMID- 25140221
TI - Enucleation of eye using finger following cannabis consumption: a case report.
AB - BACKGROUND: Enucleation is a topic discussed in psychiatry which is a self-injury
matter. Enucleation is observed as psychotic disorder due to substance abuse. In
people with mental disorders who also have substance use leading to
hallucinations and delusions, unusual eye evacuation were reported. In most
cases, enucleation was done using sharp tools. CASE REPORT: This report describes
a man suffering from psychosis after consuming hashish and has attempted to
evacuate his eyes with his finger. DISCUSSION: Given the increasing prevalence of
hashish use by young people, and false beliefs about the use of hashish in order
to withdraw other substances, preventive methods and education for young and
vulnerable people are suggested.
PMID- 25140222
TI - Nose to tail, roots to shoots: spatial descriptors for phenotypic diversity in
the Biological Spatial Ontology.
AB - BACKGROUND: Spatial terminology is used in anatomy to indicate precise, relative
positions of structures in an organism. While these terms are often standardized
within specific fields of biology, they can differ dramatically across taxa. Such
differences in usage can impair our ability to unambiguously refer to anatomical
position when comparing anatomy or phenotypes across species. We developed the
Biological Spatial Ontology (BSPO) to standardize the description of spatial and
topological relationships across taxa to enable the discovery of comparable
phenotypes. RESULTS: BSPO currently contains 146 classes and 58 relations
representing anatomical axes, gradients, regions, planes, sides, and surfaces.
These concepts can be used at multiple biological scales and in a diversity of
taxa, including plants, animals and fungi. The BSPO is used to provide a source
of anatomical location descriptors for logically defining anatomical entity
classes in anatomy ontologies. Spatial reasoning is further enhanced in anatomy
ontologies by integrating spatial relations such as dorsal_to into class
descriptions (e.g., 'dorsolateral placode' dorsal_to some 'epibranchial
placode'). CONCLUSIONS: The BSPO is currently used by projects that require
standardized anatomical descriptors for phenotype annotation and ontology
integration across a diversity of taxa. Anatomical location classes are also
useful for describing phenotypic differences, such as morphological variation in
position of structures resulting from evolution within and across species.
PMID- 25140223
TI - High level of treatment failure with commonly used anthelmintics on Irish sheep
farms.
AB - BACKGROUND: In 2013 a Technology Adoption Program for sheep farmers was
established to encourage the implementation of best management practices on sheep
farms in Ireland. There were 4,500 participants in this programme in 2013. As
part of this programme, farmers had the option to carry out a drench test to
establish the efficacy of their anthelmintic treatment. RESULTS: Flock faecal
samples were collected before and after treatment administration and
gastrointestinal nematode eggs enumerated. In total there were 1,893 participants
in the task, however only 1,585 included both a pre- and post-treatment faecal
sample. Of those, 1,308 provided information on the anthelmintic product that
they used with 46%, 23% and 28% using a benzimidazole (BZ), levamisole (LEV) and
macrocyclic lactone (ML) product respectively. The remaining farmers used a
product inapplicable for inclusion in the task such as a flukicide or BZ/LEV
combination product. Samples were included for analysis of drench efficacy if the
pre-treatment flock egg count was >=200 eggs per gram and the interval post
sampling was 10-14 days for BZ products, 4-7 days for LEV products and 14-18 days
for ML products. These criteria reduced the number of valid tests to 369, 19.5%
of all tests conducted. If the reduction post-treatment was >=95% the treatment
was considered effective. Only 51% of treatments were considered effective using
this criterion. There was a significant difference in efficacy between the
anthelmintic drug classes with BZ effective in only 30% of treatments, LEV
effective in 52% of cases and ML effective in 76% of cases. CONCLUSIONS:
Gastrointestinal nematode anthelmintic treatments, as practiced on Irish farms,
have a high failure rate. There was a significant difference between the
efficacies of the anthelmintic classes with BZ the least effective and ML the
most effective.
PMID- 25140224
TI - Metastatic penile carcinoma - an update on the current diagnosis and treatment
options.
AB - INTRODUCTION: Penile carcinoma has an incidence of 4,000 cases in Europe. The
therapy and prognosis depend decisively on the lymph node status. Lymph node
metastases are detected in 23-65% cases depending on the histopathological
pattern. Due to improved diagnostic methods an early detection of tumor stage is
possible. Multimodal therapeutic concepts can offer curability for a subset of
patients, even those suffering from advanced disease. MATERIAL AND METHODS:
Current data on penile cancer based on a selective review of the literature by
PubMed and the EAU guidelines 2009. RESULTS: Invasive diagnostic tools, such as
fine-needle biopsy (FNB) and dynamic sentinel node biopsy (DSNB), improved the
diagnosis of lymph node status considerably and reduced the morbidity in
specialized centers. The application of 18F-FDG-PET/CT for metastases detection
needs further evaluation due to inconsistent results. Inguinal lymphadenectomy is
the therapeutic standard in case of metastases proof. It was possible to reduce
the complications due to the new modified operation techniques. Patients with
extended lymph node and distant metastases have a poor prognosis. Different
systemic polychemotherapy regimes are applied currently and are associated with
poor outcome (response rates <50%) and high morbidity. Neoadjuvant chemotherapy
is recommended in patients with unresectable and relapsing lymph node metastases.
CONCLUSIONS: Currently, inconsistent therapy regimens are applied for metastatic
penile cancer. Standardization is urgently needed through the development of high
quality studies and long-term registers in order to lower the morbidity and
increase the efficiency of diagnosis and therapy.
PMID- 25140225
TI - Modern diagnostic and treatment regimens are needed to achieve the best cancer
and quality of life control.
PMID- 25140226
TI - Significance of atypical small acinar proliferation and extensive high-grade
prostatic intraepithelial neoplasm in clinical practice.
AB - INTRODUCTION: Prostate cancer (PCa) is one of the most commonly diagnosed
neoplasms in elderly men. The precancerous lesion of PCa is considered a high
grade prostate intraepithelial neoplasm (HG-PIN), while atypical small acinar
proliferation (ASAP) is commonly considered as an under-diagnosed cancer. The aim
of the study was to establish the impact of ASAP and extensive HG-PIN on pre
biopsy prostate-specific antigen (PSA) levels and the risk of cancer development
in subsequent biopseis. MATERIAL AND METHODS: The 1,010 men suspected for PCa
were included in the study based on elevated PSA, and/or positive rectal
examination. Transrectal ultrasound (TRUS) guided 10 core biopsy was performed.
In those with extensive HG-PIN or ASAP on the first biopsy, and/or elevated PSA
value, a second biopsy was performed. RESULTS: In the second biopsy, PCa was
diagnosed in 6 of 19 patients (31.57%) with extensive HG-PIN, in four of 40 (10%)
with BPH, and in 4 of 18 (22.22%) with ASAP. There was a statistically
significant difference between the values of PSA in the group of patients with
ASAP in comparison to those with benign prostate hyperplasia (BPH) (p = 0.005) as
well as in patients with HG-PIN in comparison to BPH (p = 0.02). CONCLUSIONS: A
precancerous lesion diagnosed upon biopsy causes a statistically significant
increase in the values of PSA in relation to BPH, as well as in the case of ASAP
and extensive HG-PIN. The estimate of risk of PCa diagnosis in patients with ASAP
and those with extensive HG-PIN in the first biopsy is comparable, which is why
there are no reasons for different treatment of patients with the above-mentioned
diagnoses. Both should be subjected to urgent second biopsy in around the 4-6
weeks following the initial biopsy.
PMID- 25140227
TI - Usage of invisible near infrared light (NIR) fluorescence with indocyanine green
(ICG) and methylene blue (MB) in urological oncology. Part 1.
AB - INTRODUCTION: Near infrared (NIR) technology has recently garnered much interest
as a tool for intraoperative image-guided surgery in various surgical sub
disciplines. In urology, although nascent, NIR technology is also fostering much
enthusiasm. This review discusses the two major fluorophores, indocyanine green
(ICG) and methlyene blue (MB), with NIR guidance in experimental and clinical
urology. The authors aim to illustrate and analyze the currently available
initial studies to better understand the potential and practicability of NIR
guided imaging in the diagnosis and surgical outcome improvement. In the first
part of the study we analyzed problems associated with sentinel lymph node
biopsy, NIR-guided detection and imaging of tumors. MATERIAL AND METHODS: PubMed
and Medline databases were searched for ICG and MB use in urological settings,
along with data published in abstracts of urological conferences. RESULTS:
Although NIR-guided ICG and MB are still in their initial phases, there have been
significant developments in major domains of urology, including uro-oncological
surgery: 1) sentinel lymph node biopsy, 2) detection and imaging of tumors.
CONCLUSIONS: Much like in other fields of surgical medicine, the application of
NIR technology in urology is at its early stages. Therefore, more studies are
needed to assess the true potential and limitations of the technology. However,
initial developments hint towards a pioneering tool that may influence various
aspects of urology.
PMID- 25140228
TI - Pfannenstiel incision for radical retropubic prostatectomy as a surgical and
cosmetic alternative to the midline or laparoscopic approach: A single center
study.
AB - OBJECTIVES: The Pfannenstiel incision is not a very common approach for radical
retropubic prostatectomy (RPE). This study is primarily dealing with the approach
to the prostate. MATERIAL AND METHODS: A 10-12 cm Pfannenstiel incision was made
2 fingers above the pubic bone. The rectus sheath was opened transversally and
dissected from the rectus muscle. The muscle was further on divided in the
midline; otherwise, the operation was performed the same way as the retropubic
radical prostatectomy described by Walsh [1]. The wound closure was performed in
several layers, and the skin was stapled. RESULTS: In a series of 163 RPEs, we
achieved excellent cosmetic results. Four patients developed subcutaneous
hematomas, two of them required surgical intervention, and 3 patients developed
infections that were effectively treated with antibiotics. CONCLUSIONS: Our
experience with the Pfannenstiel incision approach for radical retropubic
prostatectomy was very positive. The approach provides good exposure, heals well
with a cosmetic scar, and facilitates hernia repair through the same approach if
needed.
PMID- 25140229
TI - Adrenergic crisis due to pheochromocytoma - practical aspects. A short review.
AB - INTRODUCTION: The definitive therapy in case of pheochromocytoma is complete
surgical resection. Improper preoperative assessment and medical management
generally places the patient at risk for complications, resulting from an
adrenergic crisis. Therefore, it is crucial to adequately optimize these patients
before surgery. Optimal preoperative medical management significantly decreases
morbidity and mortality during the tumor resection. MATERIAL AND METHODS: This
review addresses current knowledge in pre- and intraoperative assessment of a
patient with pheochromocytoma. RESULTS: Before surgery the patient is
conventionally prepared with alpha-adrenergic blockade (over 10-14 days) and
subsequently, additional beta-adrenergic blockade is required to treat any
associated tachyarrhythmias. In preoperative assessment, it is obligatory to
monitor arterial blood pressure, heart rate, and arrhythmias and to restore the
blood volume to normal. CONCLUSIONS: In conclusion, due to the pathophysiological
complexity of a pheochromocytoma, the strict cooperation between the
cardiologist, endocrinologist, surgeon and the anaesthesiologist for an
uneventful outcome should be achieved in patients qualified for the surgical
removal of such a tumor.
PMID- 25140230
TI - Management and follow up of extra-adrenal phaeochromocytoma.
AB - INTRODUCTION: The prevalence of phaeochromocytoma (PCC) in patients with
hypertension is 0.1-0.6% and about 10% of PCCs are detected in extra-adrenal
tissue. The diagnosis and therapy of this rare disease detected as a
retroperitoneal tumor mass can be difficult for clinicians. MATERIAL AND METHODS:
A PubMed database was searched for the peer-reviewed articles, the listed
articles until Dec 2012 were included. Following key words were used: "extra
adrenal phaeochromocytoma", "paraganglioma", "diagnosis", "therapy", "surgery",
"genetic analysis", and "SDH mutation". RESULTS: Magnetic Resonance Imaging (MRI)
and Computed Tomography (CT) are first choice imaging tools for PCC (sensitivity
90-100%). For the validation of the diagnosis or follow up, the functional
imaging 123I-metaiodobenzylguanidine (MIBG) or Fluorine-18-L
dihydroxyphenylalanine (18F-DOPA) positron emission tomography (excellent
specificity and sensitivity of 90-100% in detection of small tumors >1-2 cm) are
used. Laparoscopic surgery with complete resection is a safe and a first choice
approach. The conversion (about 5%) to direct open operation was needed for large
lesions (>8 cm) with the suspicion of malignancy. Currently, there are no
histological criteria for distinguishing benign and malignant tumors. The genetic
testing (Sanger DNA sequencing) for hereditary syndromes (von Hippel-Lindau,
neurofibromatosis, etc.) is used for prediction of malignancy and recurrence. All
patients should get individual and risk-adapted genetic analysis and
consultation, including family members. The rate of malignancy in ePCC is about
30% (PCC about 5-10%). In patients with proven SDHB germline mutations, higher
malignancy rate, multiple PCCs and recurrences are likely. A stringent lifelong
clinical follow-up is recommended in these cases. Patients with syndromic
hereditary forms should be screened for other often associated neoplasms.
CONCLUSIONS: New imaging tools and genetic analysis are crucial to improve the
diagnosis and prognosis of phaeochromocytoma.
PMID- 25140231
TI - Diagnosis of extra-adrenal phaeochromocytoma after nephrectomy.
AB - This case describes a 50-yr-old man who was admitted to the Urology Ward upon the
suspicion of a left kidney tumor. As part of the pre-operative check-up, an
ultrasound and computed tomography of the kidneys were conducted. The results
confirmed the initial diagnosis. The postoperative diagnosis was extra-adrenal
pararenal phaeochromocytoma (ePCC) with succinate dehydrogenase complex, subunit
B (SDHB) gene mutation. During the follow-up, a second tumor was detected by 3,4
dihydroxy-6-F-18-fluoro-L-phenylalanine positron emission tomography/computed
tomography F-DOPA-PET CT that resulted in another surgery with complete resection
of the tumor. The patient and his family were counseled by a genetic laboratory
and remain under surveillance.
PMID- 25140233
TI - Lower urinary tract symptoms and their severity in men subjected to prostate
biopsy.
AB - INTRODUCTION: Lower urinary tract symptoms (LUTS) are one of most frequent
complaints among men over 50 years of age. They usually result from benign
prostate hyperplasia, which often coexists with cancer. The aim of the present
study is to evaluate prospectively the incidence of LUTS and their character in
men subjected to prostate biopsy. MATERIAL AND METHODS: Data of men who were
subjected to transrectal ultrasound guided prostate core biopsy from 1st July
2007 to 30th July 2008 in selected urological departments in Poland were
analyzed. LUTS were measured with International Prostate Symptom Score (IPSS).
RESULTS: Prostate biopsy was performed in 747 men aged between 34 and 93 years
(mean - 67.4; median - 68). LUTS of mild degree or no LUTS (<=7 IPSS points) were
reported by 29.5% of patients. PCa was found in 60.0% of them. Among men with
moderate or severe LUTS (IPSS >7 points), PCa was found in 51.4% and 55.0% of
them respectively. Median PSA was 9.5 ng/ml, 9.4 ng/ml and 12.0 ng/ml in men with
mild, moderate and severe LUTS respectively (NS). However, among men with severe
LUTS, PCa was more likely to be less differentiated and locally advanced.
CONCLUSIONS: LUTS are weak predictors of a positive result of transrectal
ultrasound guided prostate biopsy. However, there is a trend to diagnose more
locally advanced and less highly differentiated cancers among men with severe
lower urinary tract symptoms.
PMID- 25140234
TI - The presence of LUTS is not a decisive tool for deciding who should be qualified
for prostate biopsy.
PMID- 25140232
TI - Tadalafil in the management of lower urinary tract symptoms: a review of the
literature and current practices in Russia.
AB - INTRODUCTION: Strong epidemiologic evidence supports correlation between lower
urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH) and
erectile dysfunction (ED). The link has biologic plausibility given
phosphodiesterase type 5 (PDE5) expression in pelvic structures. PDE5 inhibitors
target pathophysiologic processes implicated in LUTS/BPH. MATERIAL AND METHODS:
This review highlights the efficacy and safety of the daily use of a PDE5
inhibitor tadalafil in LUTS/BPH, with a focus on LUTS/BPH medical management in
Russia. RESULTS: Alpha-blockers and phytotherapy are major components of the
current LUTS/BPH therapy in Russia. Russian regulatory authorities granted
approval for once-daily tadalafil for treatment of LUTS/BPH in January 2012. In a
pivotal study, tadalafil 5 mg once-daily significantly improved International
Prostate Symptom Score (IPSS) over 12 weeks vs. placebo (P = .004) regardless of
baseline ED severity. IPSS improvement was maintained at 12 weeks. Integrated
analysis of randomized studies showed that tadalafil 5 mg once-daily resulted in
significant symptom improvements across a range of men with LUTS/BPH. Relief of
LUTS due to tadalafil was independent of improvement in ED; improvements in IPSS
and erectile function were only weakly correlated (r = -0.229). Another pooled
analysis found similar improvement in LUTS/BPH between men with or without ED,
with non-significant P values for treatment-by-ED-status interactions for total
IPSS ( P = .73). Non-registration studies of tadalafil and alpha-blocker co
therapy in LUTS/BPH suggest an additive effect, but co-therapy is not recommended
in current tadalafil prescribing instructions. CONCLUSIONS: Tadalafil results in
symptom improvements across a range of men with LUTS/BPH and represents a new
treatment option for patients in Russia with LUTS/BPH.
PMID- 25140235
TI - Secondary infertility and the aging male, overview.
AB - INTRODUCTION: Old men preparing themselves for marriage late in their lives might
face infertility. Infertility in this group of men should be considered from a
wider perspective, as they face any age-related health troubles that include, but
are not limited to, androgen deficiency and psychological disorders that impede
early conception. This review aims to shed light on the proper approach to this
minority of secondarily infertile men. MATERIAL AND METHODS: A comprehensive
electronic English literature search was conducted, using various medical
websites and books, for the factors that cause infertility in senior fathers. The
physiology of geriatric males, together with their common comorbidities, were
discussed. RESULTS: Old men presenting with secondary infertility should be
approached differently. Aging, itself, has a significant impact on male sexual
function, sperm parameters, and fertility; all of which contribute to poor
fecundability, decreased fertilizing capacity, increased time to pregnancy,
increased rate of DNA damage, high abortion rates and increased prevalence of
fetal developmental failures. The complexity and the unknowns of the aging male
physiology, together with the interaction of obstinate diseases the patient might
have, make the issue very difficult to tackle. CONCLUSIONS: Management should
include the conventional way of treating young sufferers and further target the
underlying causes, if known, along with the provision of geriatric, psychologic,
and andrologic support.
PMID- 25140236
TI - Sexology of elderly man with secondary infertility.
PMID- 25140237
TI - Conservative management of accidental gall bladder puncture during percutaneous
nephrolithotomy.
AB - Percutaneous nephrolithotomy (PCNL) has been an excellent option for the
management of kidney stones. There have been many complications in regards to
solid organ injury during PCNL. Here we discuss an interesting case of 45-year
old woman, who underwent PCNL for right renal staghorn calculus, and had an
accidental puncture of the gall bladder. Post operatively, the patient was
conservatively managed and recovered well. A small number of cases has been
reported until now in literature.
PMID- 25140238
TI - Getting access in PNL - eyes wide shut.
PMID- 25140239
TI - Make the technology count.
PMID- 25140240
TI - Infected urachal cyst in a young adult.
AB - The urachus is the remnant of the cloaca, which in adults attaches the bladder
dome to the umbilicus. After birth it obliterates and presents as the midline
umbilical ligament. Patent urachal anomalies are usually detected in childhood.
In adults they occur very rarely and the presentation and diagnosis may be
occasionally challenging. We present and discuss the case of an infected urachal
cyst found in a 30-year-old adult.
PMID- 25140241
TI - Use of Martius flap in the complex female urethral surgery.
AB - INTRODUCTION: Objectives were to evaluate safety and patient reported perception
of the Martius fibroadipose flap for complex female urethra reconstruction.
MATERIAL AND METHODS: Patients operated with a Martius flap were contacted again
via telephone to rate their self-perception on cosmetic appearance, pain or
numbness of the flap harvest site. RESULTS: 37 women (mean age of 46.8 yrs.) were
operated with Martius flaps. Complications were limited to bleeding from the flap
bed in 19% (7/37); hematomas - 5.4% (2/37); and lymphorrhea from the labial
incision in 13.5% (5/37) and labial wound infection in 5.4% of cases (2/37). For
self-perception 65% of patients (24/37) were phone interviewed (mean follow up -
54.2 months). Only 17% of women (4/24) complained to cosmetic problems. Two
patients (8%) complained to a periodical mild pain. And 12.5% (3/24) of the women
had decreased sensation or numbness at the labia. CONCLUSIONS: Martius flap is
safe and it is not causing significant complications during female urethral
reconstruction. However, an informed consent for decreased sensation and numbness
at the flap harvesting area should be obtained.
PMID- 25140242
TI - Use of Martius flaps in complex female urethral surgery and the tethered vagina
syndrome.
PMID- 25140243
TI - Renal function recovery after laparosocopic pyeloplasty.
AB - INTRODUCTION: To observe the renal function recovery measured by diuretic
renography in short and medium follow-up of patients with transperitoneal
Anderson-Hynes laparoscopic pyeloplasty. MATERIAL AND METHODS: WE PERFORMED A
RETROSPECTIVE REVIEW FROM OUR SERIES OF LAPAROSCOPIC PYELOPLASTIES, AND WE
APPLIED THE FOLLOWING SELECTION CRITERIA: 1) to have at least two MAG3 diuretic
renography during the follow-up, performed with a gap of 4-6 months between them;
2) to have at least one year follow-up. Fulfilling these criteria, we have
selected 35 patents of 62. RESULTS: During follow-up, statistically significant
improvement comparing with the pre-surgical value has been observed in diuretic
renography in the operated kidney in all selected patients during the time of
follow up in terms of: functional uptake ratio (FUR), furosemide excretion and
total excretion. No statistically significant differences were found in excretion
time and spontaneous excretion parameters. By dividing patients in two age groups
<40 years and >40 years we found no statistically significant differences between
them in relation to the improvement of the FUR. CONCLUSIONS: Laparoscopic
pyeloplasty not only corrects the UPJO, it also may recover renal function
demonstrated after one year follow up with diuretic renography. Laparoscopic
pyeloplasty should be procedure of choice even in those patients with poor renal
function at diagnosis, whenever there are chances of recovering renal function,
regardless patients age.
PMID- 25140244
TI - Letter to the editor.
PMID- 25140245
TI - Sex and psychotropic drugs and relationship blues.
PMID- 25140246
TI - Sustained-release corticosteroid options.
AB - Sustained-release corticosteroid treatment has shown to be a promising strategy
for macular edema due to retinovascular disease (i.e., diabetes and retinal vein
occlusion) and for the treatment of noninfectious posterior uveitis. Clinicians
now have the option of three sustained-release corticosteroid implants: Ozurdex
(Allergan Inc., Irvine, CA) which releases dexamethasone and two devices that
release fluocinolone acetonide, Retisert (Bausch & Lomb, Rochester, NY), and
Iluvien (Alimera Science, Alpharetta, GA). Each has different physical
characteristics and duration effect and has been approved for different
indications. Herein we provide a summary of the current clinical knowledge
regarding these implants.
PMID- 25140247
TI - Eye movement control.
PMID- 25140248
TI - Prevalence of psychiatric morbidities in acute coronary heart disease.
AB - Introduction. Psychiatric problems and stresses may deteriorate the prognosis of
patients with IHD. So evaluating their frequency possibly will promote our
perspective regarding their vital importance in the field of consultation-liaison
psychiatry. Method and Materials. One hundred and one (101) patients with IHD
were interviewed in CCU of a general hospital by a psychiatrist to find whether
there was any relationship between cardiac events and psychiatric problems or
stresses. Results. Cardiac events were significantly more prevalent among
patients with both psychiatric problems and biological risk factors (P < 0.05).
Also, the number of patients suffering from psychiatric problems was
significantly more than cases without that (P < 0.05). There was a significant
difference between male and female patients regarding the type of stress (P <
0.01). 79% of total stresses were experienced by patients who had as well
psychiatric problems (P < 0.0001). In addition, there was significantly more
dysthymic disorder in the acute group of patients in comparison with major or
minor depressive disorder in the chronic group (P < 0.001). Conclusion. The high
prevalence of psychiatric problems and psychosocial stresses among patients with
IHD deserves sufficient attention by clinicians for detection, monitoring, and
management of them.
PMID- 25140249
TI - Light to moderate alcohol consumption is protective for type 2 diabetes mellitus
in normal weight and overweight individuals but not the obese.
AB - OBJECTIVE: To examine the association between alcohol consumption and risk of
type 2 diabetes mellitus (T2DM) overall and by body mass index. METHODS: Cross
sectional study of employed individuals. Daily alcohol intakes were calculated
from a self-administered food frequency questionnaire by 5,512 Maori, Pacific
Island, and European workers (3,992 men, 1520 women) aged 40 years and above.
RESULTS: There were 170 new cases of T2DM. Compared to the group with no alcohol
consumption and adjusting for age, sex, and ethnicity, the group consuming
alcohol had relative risks of T2DM of 0.23 (95% CI: 0.08, 0.65) in normal weight
individuals, 0.38 (0.18, 0.81) in overweight individuals, and 0.99 (0.59, 1.67)
in obese individuals. After further adjusting for total cholesterol, HDL
cholesterol, triglycerides, smoking habit, physical activity, socioeconomic
status, body mass index, and hypertension, the relative risks of T2DM were 0.16
(0.05, 0.50) in normal weight individuals, 0.43 (0.19, 0.97) in overweight
individuals, and 0.92 (0.52, 1.60) in overweight individuals. Across the
categories of alcohol consumption, there was an approximate U-shaped relationship
for new cases of T2DM. There was no significant association between alcohol
consumption and IGT. CONCLUSIONS: Alcohol consumption was protective against
diagnosis of T2DM in normal and overweight individuals but not in the obese.
PMID- 25140250
TI - Extent of Anaemia among Preschool Children in EAG States, India: A Challenge to
Policy Makers.
AB - Background. India is the highest contributor to child anemia. About 89 million
children in India are anemic. The study determines the factors that contributed
to child anemia and examines the role of the existing programs in reducing the
prevalence of child anemia particularly in the EAG states. Methods. The data from
the latest round of the National Family Health Survey (NFHS-3) is used. Simple
bivariate and multinomial logistics regression analyses are used. Results. About
70% children are anemic in all the EAG states. The prevalence of severe anemia is
the highest (6.7%) in Rajasthan followed by Uttar Pradesh (3.6%) and Madhya
Pradesh (3.4%). Children aged 12 to 17 months are significantly seven times (RR =
7.99, P < 0.001) more likely to be severely anemic compared to children of 36 to
59 months. Children of severely anemic mothers are also found to be more severely
anemic (RR = 15.97, P < 0.001) than the children of not anemic mothers.
Conclusions. The study reveals that the existing government program fails to
control anemia among preschool children in the backward states of India.
Therefore, there is an urgent need for monitoring of program in regular interval,
particularly for EAG states to reduce the prevalence of anemia among preschool
children.
PMID- 25140251
TI - Novel axillary approach for brachial plexus in robotic surgery: a cadaveric
experiment.
AB - Brachial plexus surgery using the da Vinci surgical robot is a new procedure.
Although the supraclavicular approach is a well known described and used
procedure for robotic surgery, axillary approach was unknown for brachial plexus
surgery. A cadaveric study was planned to evaluate the robotic axillary approach
for brachial plexus surgery. Our results showed that robotic surgery is a very
useful method and should be used routinely for brachial plexus surgery and
particularly for thoracic outlet syndrome. However, we emphasize that new
instruments should be designed and further studies are needed to evaluate in vivo
results.
PMID- 25140252
TI - Knowledge and perception on long acting and permanent contraceptive methods in
adigrat town, tigray, northern ethiopia: a qualitative study.
AB - Background. Long acting and permanent contraceptive methods have the potential to
reduce unintended pregnancies but the contraceptive choice and utilization in
Ethiopia are highly dominated by short term contraceptives. Objective. To assess
the knowledge and perception on long acting and permanent contraceptives of
married women and men in Northern Ethiopia. Method. A qualitative method was
conducted in Adigrat on January, 2012. Four focus group discussions with married
women and men and six in-depth interviews with family planning providers were
conducted. Content analysis was used to synthesize the data. Result.
Participants' knowledge on long acting and permanent contraceptives is limited to
recognizing the name of the methods. Most of the participants are not able to
identify permanent methods as a method of contraception. They lack basic
information on how these methods work and how they can use it. Women had fears
and rumors about each of these methods. They prefer methods which do not require
any procedure. Family planning providers stated as they have weakness on
counseling of all contraceptive choices. Conclusion. There are personal barriers
and knowledge gaps on these contraceptive methods. Improving the counseling
service program can help women to increase knowledge and avoid misconceptions of
each contraceptive choice.
PMID- 25140253
TI - High Steroid Sensitivity among Children with Nephrotic Syndrome in Southwestern
Nigeria.
AB - Recent reports from both Caucasian and black populations suggest changes in
steroid responsiveness of childhood nephrotic syndrome. This study was therefore
undertaken to determine the features and steroid sensitivity pattern of a cohort
of black children with nephrotic syndrome. Records of children managed for
nephrotic syndrome from January 2008 to April 2013 were reviewed. Details
including age, response to treatment, and renal histology were analysed. There
were 108 children (median age: 5.9 years, peak: 1-2 years), 90.2% of whom had
idiopathic nephrotic syndrome. Steroid sensitivity was 82.8% among children with
idiopathic nephrotic syndrome but 75.9% overall. Median time to remission was 7
days. Median age was significantly lower in steroid sensitive compared with
resistant patients. The predominant histologic finding in resistant cases was
focal segmental glomerulosclerosis (53.3%). No cases of quartan malaria
nephropathy or hepatitis B virus nephropathy were diagnosed. Overall mortality
was 6.5%. In conclusion, unusually high steroid sensitivity is reported among a
cohort of black children. This is likely attributable to the lower age structure
of our cohort as well as possible changing epidemiology of some other childhood
diseases. Surveillance of the epidemiology of childhood nephrotic syndrome and
corresponding modifications in practice are therefore recommended.
PMID- 25140254
TI - Occipital Artery Function during the Development of 2-Kidney, 1-Clip Hypertension
in Rats.
AB - This study compared the contractile responses elicited by angiotensin II (AII),
arginine vasopressin (AVP), and 5-hydroxytryptamine (5-HT) in isolated occipital
arteries (OAs) from sham-operated (SHAM) and 2-kidney, 1-clip (2K-1C)
hypertensive rats. OAs were isolated and bisected into proximal segments (closer
to the common carotid artery) and distal segments (closer to the nodose ganglion)
and mounted separately on myographs. On day 9, 2K-1C rats had higher mean
arterial blood pressures, heart rates, and plasma renin concentrations than SHAM
rats. The contractile responses to AII were markedly diminished in both proximal
and distal segments of OAs from 2K-1C rats as compared to those from SHAM rats.
The responses elicited by AVP were substantially greater in distal than in
proximal segments of OAs from SHAM rats and that AVP elicited similar responses
in OA segments from 2K-1C rats. The responses elicited by 5-HT were similar in
proximal and distal segments from SHAM and 2K-1C rats. These results demonstrate
that continued exposure to circulating AII and AVP in 2K-1C rats reduces the
contractile efficacy of AII but not AVP or 5-HT. The diminished responsiveness to
AII may alter the physiological status of OAs in vivo.
PMID- 25140255
TI - Acute stroke care and thrombolytic therapy use in a tertiary care center in
Lebanon.
AB - Background. Thrombolytic therapy (rt-PA) is approved for ischemic stroke
presenting within 4.5 hours of symptoms onset. The rate of utilization of rt-PA
is not well described in developing countries. Objectives. Our study examined
patient characteristics and outcomes in addition to barriers to rt-PA utilization
in a tertiary care center in Beirut, Lebanon. Methods. A retrospective chart
review of all adult patients admitted to the emergency department during a one
year period (June 1st, 2009, to June 1st, 2010) with a final discharge diagnosis
of ischemic stroke was completed. Descriptive analysis was done followed by a
comparison of two groups (IV rt-PA and no IV rt-PA). Results. During the study
period, 87 patients met the inclusion criteria and thus were included in the
study. The mean age was found to be 71.9 years (SD = 11.8). Most patients arrived
by private transport (85.1%). Weakness and loss of speech were the most common
presenting signs (56.3%). Thirty-three patients (37.9%) presented within 4.5
hours of symptom onset. Nine patients (10.3%, 95% CI (5.5-18.5)) received rt-PA.
The two groups (rt-PA versus non rt-PA) had similar outcomes (mortality,
symptomatic intracerebral hemorrhage, modified Rankin scale scores, and residual
deficit at hospital discharge). Conclusion. In our setting, rt-PA utilization was
higher than expected. Delayed presentation was the main barrier to rt-PA
administration. Public education regarding stroke is needed to decrease time from
symptoms onset to ED presentation and potentially improve outcomes further.
PMID- 25140256
TI - Isolation and characterization of bacteriophages infecting nocardioforms in
wastewater treatment plant.
AB - Activated sludge plants (ASP) are associated with the stable foaming problem
worldwide. Apart from the physical and chemical treatment methods, biological
treatment method has been least explored and may prove to be a novel and
ecofriendly approach to tackle the problem of stable foam formation. In ASP
Nocardia species are commonly found and are one of the major causes for forming
sticky and stable foam. This study describes the isolation and characterization
of three Nocardia bacteriophages NOC1, NOC2, and NOC3 for the control of Nocardia
species. The bacteriophages isolated in this study have shown promising results
in controlling foam producing bacterial growth under laboratory conditions,
suggesting that it may prove useful in the field as an alternative biocontrol
agent to reduce the foaming problem. To the best of our knowledge to date no work
has been published from India related to biological approach for the control of
foaming.
PMID- 25140257
TI - Iranian patients require more pertinent care to prevent type 2 diabetes
complications.
AB - Background. Accurate care of patients with type 2 diabetes may reduce risk of
complications. This study was conducted to envisage current status of cares that
are provided for a sample of Iranian patients with type 2 diabetes and highlight
the domains that need to be focused on in the country's national type 2 diabetes
care program. Methods. Behavioral risk factors and diabetes related complications
were investigated among 234 randomly selected type 2 diabetic patients residing
in the city of Khoy, Northwest of Iran. Data were collected by a semistructured
questionnaire in face to face or telephone interview. Proportions and confidence
intervals of the observed difference were calculated by the Confidence Interval
Analysis (CIA) software version 2.2.0. Results. Diabetes complications were
evident amongst 67.2% of the patients. Inappropriate dietary pattern,
insufficient physical activity, and anxiety were reported by 26.5%, 74.8%, and
69.7% of the respondents. Quality of life was reported to be affected in 94.6% of
the respondents but its burden was significantly greater in females (P < 0.001,
95% CI of the difference: -0.75 to -0.53). Conclusions. The findings reflect
discrepancies in providing the required care for the studied Iranian patients
with type 2 diabetes to prevent their disease's complications.
PMID- 25140259
TI - Left ventricle pseudoaneurysm: contribution of multimodality imaging to the
diagnosis.
AB - The left ventricle pseudoaneurysm is an anomaly of the left ventricle and is
severed and joined with a pocket look. There may be secondary to a myocardial
infarction, trauma, or surgical procedure. Sometimes the cause is not found.
Complications are heart failure, arrhythmias, vascular embolism, and sudden
death. The treatment is surgical only. The authors report the case of a black
patient of 64 years old, without medical history, had seen to a deformation of
the cardiac shadow in radiography. The left ventricle pseudoaneurysm and in situ
thrombus are visualized in echocardiography and CT scan. The patient is waiting
for heart surgery.
PMID- 25140260
TI - Novel Use of the GuideLiner Catheter to Deliver Rotational Atherectomy Burrs in
Tortuous Vessels.
AB - Rotational atherectomy (RA) for heavily calcified lesions is essential for
improved stent delivery and stent expansion. In tortuous vessels it is often
difficult to advance the burr without rotation and possible injury to the
endothelium of healthy vessel. The GuideLiner catheter, a child in mother
catheter, has recently been used to allow for increased support for delivery of
stents through tortuous vessels. We report a novel use of the GuideLiner for the
delivery of an RA burr in tortuous vessels requiring increased guide support.
PMID- 25140258
TI - The interplay between reproductive social stimuli and adult olfactory bulb
neurogenesis.
AB - Adult neurogenesis is a striking form of structural plasticity that adapts the
brain to the changing world. Accordingly, new neuron production is involved in
cognitive functions, such as memory, learning, and pattern separation. Recent
data in rodents indicate a close link between adult neurogenesis and reproductive
social behavior. This provides a key to unravel the functional meaning of adult
neurogenesis in biological relevant contexts and, in parallel, opens new
perspectives to explore the way the brain is processing social stimuli. In this
paper we will summarize some of the major achievements on cues and mechanisms
modulating adult neurogenesis during social behaviors related to reproduction and
possible role/s played by olfactory newborn neurons in this context. We will
point out that newborn interneurons in the accessory olfactory bulb (AOB)
represent a privileged cellular target for social stimuli that elicit
reproductive behaviors and that such cues modulate adult neurogenesis at two
different levels increasing both proliferation of neuronal progenitors in the
germinative regions and integration of newborn neurons into functional circuits.
This dual mechanism provides fresh neurons that can be involved in critical
activities for the individual fitness, that is, the processing of social stimuli
driving the parental behavior and partner recognition.
PMID- 25140261
TI - Correction of multiple canine impactions by mixed straightwire and cantilever
mechanics: a case report.
AB - Background. This case report describes the orthodontic treatment of a woman, aged
17 years, with a permanent dentition, brachyfacial typology, Angle Class I, with
full impaction of two canines (13,33), and a severe ectopy of the maxillary left
canine. Her main compliant was the position of the ectopic teeth. Methods.
Straightwire fixed appliances, together with cantilever mechanics, were used to
correct the impaired occlusion and to obtain an ideal torque control. Results and
Conclusion. The treatment objectives were achieved in 26 months of treatment. The
impactions were fully corrected with an optimal torque. The cantilever mechanics
succeeded in obtaining tooth repositioning in a short lapse of time. After
treatment, the dental alignment was stable.
PMID- 25140262
TI - A paradoxical triad: scapulothoracic dissociation with clavicle and humeral shaft
fractures.
AB - Scapulothoracic dissociation involves varying degree of discontinuity of the
upper extremity from its truncal attachment. An eighteen-year-old male presented
to the accident and emergency department following a motor vehicle accident where
he was hit by a four wheeler while riding a two wheeler. He had tenderness and
deformity over the left clavicle and the left humerus. He was unable to perform
active wrist and finger dorsiflexion. A CT subsequently revealed a grade 2
splenic laceration. The splenic laceration was treated conservatively. As his
general condition improved, he was gradually weaned off the ventilator and his
left upper limb neurology was reassessed. He had isolated radial nerve palsy with
an otherwise intact brachial plexus. He underwent internal fixation of the
clavicle and the humerus. At 4 months after injury the EMG/NCV report showed
signs of renervation of the radial nerve, and the fracture progressed to an
uneventful union. This prior unreported triad of scapulothoracic dissociation
with ipsilateral clavicular and humeral fractures may represent a parody. An
apparent increase in the severity of skeletal injury was associated with a
paradoxical decrease in the severity of neurovascular injury. We report this case
to create awareness among orthopedic surgeons and emergency physicians about the
clinical presentation of such injuries.
PMID- 25140263
TI - Bicondylar hoffa fracture successfully treated with headless compression screws.
AB - Bicondylar coronal plane fracture, eponymically named Hoffa fractures, is an
extremely rare injury. We present a case of isolated unilateral bicondylar Hoffa
fracture that was successfully treated with open reduction and internal fixation
using headless compression screws with satisfactory results. We inserted
posteroanteriorly oriented Acutrak screws perpendicular to the fracture plane via
lateral parapatellar arthrotomy, which provided excellent compression across the
fracture.
PMID- 25140264
TI - Bilateral atypical femoral fractures in a patient with multiple myeloma treated
with intravenous bisphosphonate therapy.
AB - Bisphosphonates are currently the standard approach to managing bone disease in
multiple myeloma. Bisphosphonates have high bone affinity that inhibits
osteoclastic activity and additionally reduces the growth factors released from
malignant or osteoblastic cells, thereby impairing abnormal bone remodeling which
leads to osteolysis. However, patients of multiple myeloma may be at a higher
risk of atypical femoral fractures because the treatment for malignant myeloma
requires notably higher cumulative doses of bisphosphonates. Here we present a
patient with bilateral atypical femoral fractures and multiple myeloma treated
with intravenous bisphosphonate therapy.
PMID- 25140265
TI - Pleomorphic adenomas of the parapharyngeal space.
AB - Background. Parapharyngeal space is one of potential facial planes for neoplasms
and infections and represents less than 1% of all head and neck tumours.
Occurrence of the pleomorphic adenoma in the parapharyngeal space is a rarity.
Case Presentation. Here, three giant pleomorphic adenomas of different sizes
occupying the parapharyngeal space in three patients are reported. Extensive
preoperative diagnostic workup was done in order to verify the nature and size of
the tumour and the proximity to the large vessels. Review of the literature,
clinical features, pathology, radiological findings, and treatment of these
tumours are discussed. Conclusion. The excision of the tumor through
submandibular transcervical approach, without cutting the mandible, turned out to
be a safe and radical approach in all three cases.
PMID- 25140266
TI - Tegmen tympani defect and brain herniation secondary to mastoid surgery: case
presentation.
AB - Brain herniation into the middle ear is very rarely seen. In addition to reasons
like congenital factors, trauma, and infection, tegmen defect may develop as a
result of iatrogenic events secondary to chronic otitis media surgery with or
without cholesteatoma. Since it may cause life-threatening complications,
patients must be evaluated and monitored for tegmen defect. In this paper,
diagnosis and treatment of a brain herniation case due to iatrogenic tegmen
defect were described along with relevant literature.
PMID- 25140267
TI - Gitelman Syndrome in a School Boy Who Presented with Generalized Convulsion and
Had a R642H/R642W Mutation in the SLC12A3 Gene.
AB - An 8-year-old Japanese boy presented with a generalized convulsion. He had
hypokalemia (serum K 2.4 mEq/L), hypomagnesemia, and metabolic alkalosis (BE 5.7
mmol/L). In addition, his plasma renin activity was elevated. He was tentatively
diagnosed with epilepsy on the basis of the electroencephalogram findings and was
treated by potassium L-aspartate and carbamazepine to control the hypokalemia and
seizure, respectively. However, a year later, the patient continued to have
similar abnormal laboratory data. A presumptive diagnosis of Gitelman syndrome
(GS) was then made and the patient's peripheral blood mononuclear cells were
subjected to sequence analysis of the SLC12A3 gene, which encodes a thiazide
sensitive sodium-chloride cotransporter. The patient was found to have compound
heterozygous mutations, namely, R642H inherited from his father and R642W
inherited from his mother. Thus, if a patient shows persistent hypokalemia and
metabolic alkalosis, GS must be considered, even if the patient exhibits atypical
clinical symptoms.
PMID- 25140268
TI - High-dose subcutaneous immunoglobulins for the treatment of severe treatment
resistant polymyositis.
AB - Polymyositis is a rare debilitating condition characterized by chronic
inflammation and muscle weakness. Standard treatments include corticosteroids and
immunosuppressants; however, resistance to these regimens may develop.
Intravenous immunoglobulins (IVIg) are thus recommended for patients with drug
resistant polymyositis. The patient presented a resistant polymyositis with
severe muscle weakness, increasing dysphagia, and significant loss in weight.
Subcutaneous immunoglobulins (SCIg) were initiated after failure of steroids and
immunosuppressive drugs. SCIg was given twice per week (2 then 1.3 g/kg/month).
Clinical recovery was observed within 2 months after the SCIg initiation. After
several injections, the patient showed a progressive improvement in muscle
strength. Serum creatine kinase activity decreased to normal levels, and
dysphagia was resolved. The SC injections were generally well tolerated and good
patient satisfaction was reported. This promising observation suggests that SCIg
may be useful in active and refractory polymyositis.
PMID- 25140269
TI - Giant bilateral adrenal myelolipoma with congenital adrenal hyperplasia.
AB - Myelolipomas are rare and benign neoplasms, predominant of the adrenal glands,
consisting of adipose and mature hematopoietic tissue, commonly discovered
incidentally with increased use of radiologic imaging. Few cases of giant
bilateral adrenal masses are reported, especially in the setting of congenital
adrenal hyperplasia (CAH). We report the case of a 39-year-old male with a
history of CAH secondary to 21-alpha hydroxylase deficiency on steroids since
childhood, self-discontinued during adolescence, presenting with abdominal
distension, fatigue, decreased libido, and easy bruising. Imaging revealed giant
bilateral adrenal masses. He subsequently underwent bilateral adrenalectomy found
to be myelolipomas measuring 30 * 25 * 20 cm on the left and weighing 4.1 kg and
25 * 20 * 13 cm on the right and weighing 2.7 kg. Adrenal myelolipomas are found
to coexist with many other conditions such as Cushing's syndrome, Addison's
disease, and CAH. We discuss the association with high adrenocorticotropic
hormone (ACTH) states and review the studies involving ACTH as proponent leading
to myelolipomas. Massive growth of these tumors, as in our case, can produce
compression and hemorrhagic symptoms. We believe it is possible that self
discontinuation of steroids, in the setting of CAH, may have resulted in the
growth of his adrenal masses.
PMID- 25140270
TI - Huge Trombus including Left Renal Vein, Ovarian Vein, and Inferior Vena Cava
Mimicking Renal Colic.
AB - A 31-year-old female presented with acute left flank pain; she had a C/S at the
postpartum day 24. Ureteral stone was suspected but ultrasound examination was
normal. Then Doppler ultrasound revealed a trombus in left renal vein and
inferior vena cava. Contrast enhanced MDCT scan showed swelled and nonfunctional
left kidney, a trombus including distal part of left ovarian vein, left renal
vein, and inferior vena cava. We started anticoagulation treatment. Further
examination revealed diagnosis of chronic myeloproliferative disease. The trombus
was completely recanalized at 3-month followup.
PMID- 25140271
TI - SIMPLE Technique of Laparoscopic Nephrectomy for Ectopic Nonfunctioning Pelvic
Kidney Secondary to Pelviureteric Junction Obstruction: A Feasible and Safe
Technique.
AB - Ectopic kidneys are rare developmental anomalies. Anomalous blood supply of the
pelvic ectopic kidneys poses a problem for a minimally invasive surgery. Although
laparoscopic nephrectomies have been described for symptomatic nonfunctioning
pelvic ectopic kidney, this is the first case report that highlights the safety
and feasibility of SIMPLE technique of laparoscopic nephrectomy in a pelvic
kidney.
PMID- 25140272
TI - A case of the nutcracker syndrome developed after delivery.
AB - We report a case of nutcracker syndrome that developed after delivery. A 32-year
old woman visited our clinic complaining of gross hematuria 4 months after
delivery. Urethrocystoscopic examination failed to show hematuria coming from the
ureteral orifice; however, enhanced computed tomography revealed the compression
of the left renal vein between the aorta and superior mesenteric artery.
Therefore, we diagnosed her with nutcracker syndrome and conservatively observed
her. The macrohematuria disappeared by itself after 1 month. This is the first
report to describe a case of nutcracker syndrome that developed after delivery.
PMID- 25140273
TI - Spontaneous postmenopausal urethral prolapse treated surgically and successfully.
AB - Urethral prolapse (UP) is a circular complete eversion of the distal urethral
mucosa through the external meatus. It is a rare condition seen mostly in African
American premenarcheal girls. Both a medical and a surgical approach to this
condition have been described. We present a case of a spontaneous urethral
prolapse in a 60-year-old postmenopausal Caucasian woman, who failed medical
management and underwent successful surgical management. The patient is
asymptomatic 18 months following the procedure.
PMID- 25140274
TI - Fahr syndrome unknown complication: overactive bladder.
AB - A 38-year-old male patient was admitted to our outpatient department because of
frequency and urgency incontinence. During evaluation it was detected that the
patient was suffering from frequency which was progressive for one year, feeling
of incontinence, and urgency incontinence. There was no urologic pathology
detected in patient's medical and family history. Neurologic consultation was
requested due to his history of boredom, reluctance to do business, balance
disorders, and recession for about 3 years. Brain computerized tomography (CT)
scan revealed that amorphous calcifications were detected in the bilaterally
centrum semiovale, basal ganglia, capsula interna, thalami, mesencephalon, pons
and bulbus, and the bilateral cerebellar hemispheres. We have detected
spontaneous neurogenic detrusor overactivity without sphincter dyssynergia after
evaluating the voiding diary, cystometry, and pressure flow study. We consider
the detrusor overactivity which occurred one year after the start of the
neurological symptoms as the suprapontine inhibition and damage in the axonal
pathways in the Fahr syndrome.
PMID- 25140275
TI - How aortic stiffness in postmenopausal women is related to common cardiovascular
risk factors.
AB - Objective. Our study investigates major common cardiovascular risk factors
relation with aortic stiffness on 269 postmenopausal women by global pulse wave
velocity (PWVg), useful to relate PWVg to risk of major cardiovascular events.
Patients and Methods. Women were categorized as hypertensive (H),
hypercholesterolemic (C), or diabetic (D). Aortic stiffness was assessed by PWVg
measured with pulsed Doppler, at the left ventricular outflow tract (LVOT) and at
the right common femoral artery. Results. All population mean PWVg was 8.2 m/s.
85 (26.5%) women were H; mean PWVg was 7.9 m/s. HC women were 118 (36.7%), with
mean PWVg 8.3 m/s. HD women were 30 (9.5%), with mean PWVg 7.8 m/s. HDC women
were 36 (11.2%), with mean PWVg 9.3 m/s. 52 (16.1%) menstruate women without risk
factor were control group (CG), with mean PWVg 6.5 m/s. Highly significant was
the statistical difference in PWVg between HDC women and each other group: P <
0.0005 versus CG; P < 0.01 versus H; P < 0.03 versus HC, and P < 0.05 versus HD.
No difference in PWG was observed comparing the other groups. There was
difference for age among all groups, except for CG, made by younger women.
Conclusion. PWVg was highly increased in postmenopausal women affected by
hypertension, diabetes, and hypercholesterolemia all at once. Hypertension is the
major determinant for PWVg. The only addition of diabetes or hypercholesterolemia
did not increase significantly PWVg. Our study supports the usefulness of the
assessment of aortic stiffness as a marker of cardiovascular disease.
PMID- 25140276
TI - Automated system for kinetic analysis of particle size distributions for
pharmaceutically relevant systems.
AB - Detailing the kinetics of particle formation for pharmaceutically relevant
solutions is challenging, especially when considering the combination of
formulations, containers, and timescales of clinical importance. This paper
describes a method for using commercial software Automate with a stream-selector
valve capable of sampling container solutions from within an environmental
chamber. The tool was built to monitor changes in particle size distributions via
instrumental particle counters but can be adapted to other solution-based
sensors. The tool and methodology were demonstrated to be highly effective for
measuring dynamic changes in emulsion globule distributions as a function of
storage and mixing conditions important for parenteral nutrition. Higher levels
of agitation induced the fastest growth of large globules (>=5 MUm) while the
gentler conditions actually showed a decrease in the number of these large
globules. The same methodology recorded calcium phosphate precipitation kinetics
as a function of [Ca(2+)] and pH. This automated system is readily adaptable to a
wide range of pharmaceutically relevant systems where the particle size is
expected to vary with time. This instrumentation can dramatically reduce the time
and resources needed to probe complex formulation issues while providing new
insights for monitoring the kinetics as a function of key variables.
PMID- 25140277
TI - Relationship between Nutrition Knowledge and Physical Fitness in Semiprofessional
Soccer Players.
AB - Whereas nutrition has a crucial role on sport performance, it is not clear to
what extent nutrition knowledge is associated with physical fitness. The aim of
this study was to examine the current level of nutrition knowledge of soccer
players and whether this level is associated with physical fitness. Soccer
players (n = 185, aged 21.3 +/- 4.9 yr, weight 72.3 +/- 8.4 kg, and height 177.5
+/- 6.4 cm) performed a battery of physical fitness tests (sit-and-reach test,
SAR; physical working capacity in heart rate 170, PWC170; and Wingate anaerobic
test, WAnT) and completed an 11-item nutrition knowledge questionnaire (NKQ). Low
to moderate Pearson correlations (0.15 < r < 0.34, p < 0.05) of NKQ with age,
weight, height, fat free mass (FFM), SAR, peak power, and mean power of WAnT were
observed. Soccer players with high score in NKQ were older (4.4 yr (2.2; 6.6),
mean difference (95% confidence intervals)) and heavier (4.5 kg (0.6; 8.3)) with
higher FFM (4.0 kg (1.1; 6.8)) and peak power (59 W (2; 116)) than their
counterparts with low score. The moderate score in the NKQ suggests that soccer
players should be targeted for nutrition education. Although the association
between NKQ and physical fitness was low to moderate, there were indications that
better nutrition knowledge might result in higher physical fitness and,
consequently, soccer performance.
PMID- 25140278
TI - Understanding thoracic outlet syndrome.
AB - The diagnosis of thoracic outlet syndrome was once debated in the world of
vascular surgery. Today, it is more understood and surprisingly less infrequent
than once thought. Thoracic outlet syndrome (TOS) is composed of three types:
neurogenic, venous, and arterial. Each type is in distinction to the others when
considering patient presentation and diagnosis. Remarkable advances have been
made in surgical approach, physical therapy, and rehabilitation of these
patients. Dedicated centers of excellence with multidisciplinary teams have been
developed and continue to lead the way in future research.
PMID- 25140279
TI - The value of neuromonitoring in cervical spine surgery.
PMID- 25140281
TI - "From writing illegibly to composing fiction: The story of a blind man with 20/20
vision".
PMID- 25140280
TI - Case comparison and literature review of glioblastoma: A tale of two tumors.
AB - BACKGROUND: Diagnosis of glioblastoma multiforme (GBM) includes a heterogeneous
group of tumors. We describe two cases with histopathologically and molecularly
similar tumors, but very different outcomes. We attempt to illustrate the need
for improved prognostic markers for GBM. CASE DESCRIPTION: Two patients with
similar molecular profiles were retrospectively identified. The following markers
were assessed: O (6)-methylguanine DNA methyltransferase (MGMT) methylation,
isocitrate dehydrogenase (IDH) 1 and 2 status, epidermal growth factor receptor
(EGFR) amplification, phosphatase and tensin homolog (PTEN) status, Ki-67, p53,
and 1p/19q status. Each patient was assigned a Karnofsky performance score at
presentation. Case 1 (62-year-old male) was a right temporal lobe glioblastoma
with a molecular profile of amplified EGFR, normal PTEN, no IDH1/2 mutation,
28.7% MGMT promoter methylation, 5-20% Ki-67, 1p deletion, and 19q intact. The
patient underwent resection followed by radiation therapy and 2 years of
chemotherapy, and was asymptomatic and tumor free 5 years post diagnosis. Tumor
eventually recurred and the patient expired 72 months after initial diagnosis.
Case 2 (63-year-old male) was a right frontal white matter mass consistent with
glioblastoma with a molecular profile of amplified EGFR, absent PTEN, no IDH1/2
mutation, 9.9% MGMT promoter methylation, 5-10% Ki-67, and 1p/19q status
inconclusive. A radical subtotal resection was performed; however, 2 weeks later
symptoms had returned. Subsequent imaging revealed a tumor larger than at
diagnosis. The patient expired 3 months after initial diagnosis. CONCLUSION: The
need for formulating more robust means to classify GBM tumor subtypes is
paramount. Standard histopathologic and molecular analyses are costly and did not
provide either of these patients with a realistic appraisal of their prognosis.
Individualized whole genome testing similar to that being reported for
medulloblastoma and other tumors may be preferable to the array of tests as
currently utilized.
PMID- 25140282
TI - Johannes Vermeer of Delft [1632-1675] and vision in neuroendoscopy.
AB - BACKGROUND: Johannes Vermeer of Delft [1632-1675] was one of the greatest Masters
of the Dutch Golden Age who was intensely preoccupied with the behavior of light
and other optical effects and was entitled "The Master of Light". He fastidiously
attended to the subtleties of visual expression through geometry, composition,
and precise mastery of the rules of perspective. It has been our impression that
some visual similarity does exist between neuroendoscopic images and some of
Vermeer's paintings. Such a relation could be explained by the fact that optical
devices are utilized in producing both types of display. METHODS: We reviewed the
pertinent medical and art literature, observed some video clips of our endoscopy
cases, and inspected digital high resolution images of Vermeer's paintings in
order to elaborate on shared optical phenomena between neuroendoscopic views and
Vermeer's paintings. RESULTS: Specific optical phenomena are indeed shared by
Johannes Vermeer's works and neuroendoscopic vision, namely light and color
effects as well as the rules of perspective. CONCLUSION: From the physical point
of view, the possibility that a camera obscura inspired Vermeer's artistic
creation makes the existence of a visual link between his paintings and the
endoscopic views of the intracranial cavity comprehensible.
PMID- 25140283
TI - Colloid cysts posterior and anterior to the foramen of Monro: Anatomical features
and implications for endoscopic excision.
AB - BACKGROUND: Colloid cysts are usually located at the rostral part of the third
ventricle in proximity to the foramina of Monro. Some third ventricular colloid
cysts, however, attain large sizes, reach a very high distance above the roof of
the third ventricle, and pose some challenges during endoscopic excision. These
features led to the speculation that for such a pattern of growth to take place,
the points of origin of these cysts should be at areas away from the foramina of
Monro at which some anatomical "windows" exist that are devoid of compact,
closely apposed forniceal structures. METHODS: A review of the literature on
anatomical variations of the structures in the vicinity of the roof of the third
ventricle and on reported cases with similar features was conducted. RESULTS:
Colloid cysts may grow vertically up past the roof of the third ventricle through
anatomical windows devoid of the mechanical restraint of the forniceal
structures. CONCLUSION: Some anatomical variations of the forniceal structures
may allow unusually large sizes and superior vector of growth of a retro- or post
foraminal colloid cyst. Careful preoperative planning and knowledge of the
pertinent pathoanatomy of these cysts before endoscopic excision is very
important to avoid complications.
PMID- 25140284
TI - Angio negative spontaneous subarachnoid hemorrhage: Is repeat angiogram required
in all cases?
AB - BACKGROUND: In some cases of spontaneous subarachnoid hemorrhage (SAH), the cause
of bleed remains obscure on initial evaluation. These patients may harbor
structural lesions. We aim to determine the utility of repeat angiogram in these
subsets of patients. METHODS: In this prospective study, patients with SAH with a
negative computed tomographic angiogram (CTA) and digital subtraction angiogram
(DSA) were included. A repeat angiogram was done after 6 weeks of initial
angiogram. Patients were divided into perimesencephalic SAH (PM-SAH) and diffuse
classic SAH (Classic-SAH) groups. Outcome was determined by modified Rankin score
(mRS). RESULTS: A total of 22% (39/178) of all SAH were angio-negative. A total
of 90% (n = 35) of these were in Hunt and Hess grade 1-3. A total of 22 patients
had PM-SAH and 17 had a Classic-SAH. Repeat angiogram did not reveal any
pathology in the PM-SAH group, whereas two patients with Classic-SAH were found
to have aneurysms. At 6 months follow-up, 95% patients of PM-SAH and 83.3% of
Classic-SAH had mRS of 0. CONCLUSION: Repeat angiogram is probably not necessary
in patients of PM-SAH and they tend to have better outcome. Classic-SAH pattern
of bleed is associated with fair chances of an underlying pathology and a repeat
angiogram is recommended and these cases and they have poorer outcome.
PMID- 25140285
TI - Giant asymptomatic mastoid pneumocele producing a scalp swelling: A rare case
report.
AB - BACKGROUND: Intraosseous collections of air are rare in comparison to the extra
osseous collection. Pneumoceles are rare entities defined as enlarged pneumatized
air sinuses or air cells, with focal or diffuse thinning of the surrounding bony
walls. They may affect mastoid air cells and any of the paranasal sinuses. CASE
DESCRIPTION: We report a rare case of extensive mastoid pneumatisation in a young
male patient. Patient was completely asymptomatic with swelling as the main
complaint. Short history of development raised suspicion for a malignant lesion.
Cholesteatoma was also taken as a differential diagnosis. However, computed
tomography (CT) scan showed gross expansion of mastoid air cells with no lesion
inside it. The walls of mastoid were markedly thinned out, making the diagnosis
as pneumocele. In spite of a large swelling, conservative treatment was adopted
in view of no symptoms and was advised follow-up regularly to detect any possible
complications. CONCLUSION: Our case was interesting in that rare mastoid
pneumoceles can be totally asymptomatic and can be large enough to raise concern
for a malignant lesion. Literature shows that such mastoid pneumocele are
symptomatic and require active intervention. Our asymptomatic mastoid pneumocele
is a rare instance requiring no surgical procedure and was followed-up. Overall,
such lesions should be treated as normal variants of physiological mastoid.
PMID- 25140286
TI - Complete resolution of steroid-resistant organizing pneumonia associated with
myelodysplastic syndrome following allogeneic hematopoietic cell transplantation.
AB - Pulmonary complications in patients with hematological malignancies are often
caused by infection but are sometimes associated with an underlying disease such
as organizing pneumonia (OP). Here, we report a case of life-threatening steroid
resistant OP associated with myelodysplastic syndrome (MDS) and successfully
performed allogeneic hematopoietic cell transplantation (HSCT). A 33-year-old
female with refractory anemia with excess blasts-1 that had progressed from
refractory anemia with ringed sideroblasts and concomitant Sweet's syndrome was
admitted. Multiple pulmonary infiltrates were revealed on a chest computed
tomography scan, which progressively worsened even after chemotherapy and
corticosteroid therapy. No evidence of infection was observed in bronchoalveolar
lavage fluid. A histological examination of a transbronchial lung biopsy specimen
showed lymphocyte invasion with fibrosis, indicating that the pulmonary
infiltrates were OP associated with MDS. Before transplantation, she suffered
from respiratory failure and required oxygen supplementation. She developed
idiopathic pneumonitis syndrome on day 61 that responded well to corticosteroid
therapy, and the OP pulmonary infiltrates improved gradually after HSCT, She was
discharged on day 104 and is well without recurrence of OP or MDS 2 years after
HSCT.
PMID- 25140288
TI - Design of static synchronous series compensator based damping controller
employing invasive weed optimization algorithm.
AB - This paper proposes designing of Static Synchronous Series Compensator (SSSC)
based damping controller to enhance the stability of a Single Machine Infinite
Bus (SMIB) system by means of Invasive Weed Optimization (IWO) technique.
Conventional PI controller is used as the SSSC damping controller which takes
rotor speed deviation as the input. The damping controller parameters are tuned
based on time integral of absolute error based cost function using IWO.
Performance of IWO based controller is compared to that of Particle Swarm
Optimization (PSO) based controller. Time domain based simulation results are
presented and performance of the controllers under different loading conditions
and fault scenarios is studied in order to illustrate the effectiveness of the
IWO based design approach.
PMID- 25140287
TI - Development of a novel cellular model of Alzheimer's disease utilizing
neurosphere cultures derived from B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J embryonic mouse
brain.
AB - Increased production, oligomerization and aggregation of amyloid-beta (Abeta)
peptides are hallmark pathologies of Alzheimer's disease (AD). Expressing
familial AD mutations (amyloid precursor protein and/or presenilins mutations),
the Abeta-pathologies of AD has been recapitulated in animal models of AD. Very
few primary cell culture-based models of AD are available and they exhibit very
weak Abeta-pathologies compared to what is seen in AD patients and animal models
of AD. CNS stem/progenitor cells are present in both embryonic and adult brains.
They can be isolated, grown as neurospheres and differentiated into neurons,
astrocytes and oligodendrocytes. It is not yet known whether CNS stem/progenitor
cells can support the production of Abeta peptides in culture. In this report, we
have established Abeta-pathologies such as production, secretion, oligomerization
and aggregation of Abeta peptides utilizing neurosphere cultures to create a new
cellular model of AD. These cultures were developed from E15 embryonic brains of
transgenic mice carrying the Swedish mutations in humanized mouse APP cDNA and
the exon-9 deleted human presenilin 1 cDNA both regulated by mouse prion protein
gene (Prnp) promoter. Results demonstrated the expression of transgene
transcripts, APPswe protein and its processed products only in transgene positive
neurosphere cultures. These cultures generate and secrete both Abeta40 and
Abeta42 peptides into culture medium at levels comparable to the Abeta load in
the brain of AD patients and animal models of AD, and produce pathogenic
oligomers of Abeta peptides. The Abeta42/Abeta40 ratio in the medium of transgene
positive neurosphere cultures is higher than any known cellular models of AD.
Conformation dependent immunocytochemistry demonstrated the possible presence of
intracellular and extracellular aggregation of Abeta peptides in neurosphere
cultures, which are also seen in AD brain and animal models of AD. Collectively,
our neurosphere cultures provide robust Abeta-pathologies of AD better than
existing cellular model of Alzheimer's disease.
PMID- 25140289
TI - Third degree formic acid chemical burn in the treatment of a hand wart: a case
report and review of the literature.
AB - OBJECTIVE: Cutaneous warts are very common and a large variety of topical
treatments and drugs can be employed to cure these skin injuries that can arise
on any part of the body. But are these products really safe? METHOD: We performed
a case description and PubMed literature review using key words "wart," "chemical
burn," and "formic acid." All articles in English and French were selected.
RESULTS: This is the first report of a chemical burn by formic acid in the
treatment of warts. Numerous topical treatments for cutaneous warts are available
with many new drugs appearing every year. However, only a few treatments have
proven their effectiveness, such as salicylic acid or cryotherapy with liquid
nitrogen that are commonly used. Moreover, most cutaneous warts will resolve
spontaneously without any treatment and several products, including topical acids
and cryotherapy devices, presented adverse effects such as chemical burns or
frostbites so demonstrating that even frequently used treatments can be harmful.
CONCLUSION: Topical treatments used for wart removal are not without risk even if
some products are sold without prescription. For self-treatment products, we
recommend enhanced warning by the pharmacist about the risks involved.
PMID- 25140290
TI - Medication in nursing homes in Alsace: a preferential list of drugs obtained by
consensus.
AB - ABSTRACT: In order to improve patient care, OMEDIT (Observatory of drugs, medical
devices and therapeutic innovation) Alsace, conducted a study to develop a
Preferential list of Drugs adapted to the Elderly (PDE list) in nursing homes.
The study conducted from December 2011 to June 2012 was organized in 4 phases: 1)
creation of a preliminary list of drugs from those currently used in nursing
homes in Alsace, 2) application of a two-round Delphi process to evaluate the
preliminary list involving mobilization of experts from different backgrounds
(geriatricians, general practitioners, pharmacists ...), 3) identification of
molecules considered in literature as potentially inappropriate, 4) generation of
a final PDE list, including information concerning proper use of drugs for
prescription and administration. 53 experts participated in the study. In the
first round, 338 drugs were on the preliminary list, 246 were considered as
appropriate by experts and 28 as inappropriate. 64 drugs without consensus were
submitted to a second round. 32 of them were considered as inappropriate and 32
others remained on the list with no consensus. These last 32 were evaluated by
OMEDIT and 3 were considered as appropriate drugs for the elderly. Totally, 252
drugs constitute the final PDE list from our study. The PDE list constitutes a
new guide for optimization of both prescription and administration of drugs in
nursing homes and could help reduce misuses and poly-medication, which are
constant preoccupations to avoid adverse drug reactions in elderly. KEY POINTS: ?
The study was carried out with the aim to create a Preferential list of Drugs
adapted to the Elderly (PDE list) in nursing homes using a modified Delphi
method. ? The PDE list constitutes a new guideline to harmonize practices in
nursing homes and to help physicians and nurses to achieve best possible care
management.
PMID- 25140291
TI - Pneumococcal-meningitis associated acute disseminated encephalomyelitis (ADEM) -
case report of effective early immunotherapy.
AB - INTRODUCTION: Unvaccinated patients with history of splenectomy are prone to
fulminant courses of Streptococcus pneumoniae-associated bacterial meningitis.
Besides direct brain damage those patients may additionally suffer from
parainfectious syndromes, notably vasculitis and acute disseminated
encephalomyelitis (ADEM). Differentiation and treatment of these immunological
reactions is challenging. METHODS: Case report. RESULTS: A 61 year-old woman with
history of splenectomy without vaccination for S. pneumoniae presented with
progressive headache and meningism. CSF-analysis revealed pleocytosis with
microbiological evidence for pneumococcal meningitis. After unsuspicious initial
cranial CT imaging and initiation of appropriate antibiotic therapy, MRI two days
later showed widespread FLAIR- and T2-hyperintense white matter lesions that
further progressed upon follow-up MRI and that fulfilled imaging criteria of
ADEM. Meanwhile the patient deteriorated and required mechanical ventilation.
Cranial angiography showed no signs of vasculitis or vasospasms. Screening for
autoimmune diseases remained negative, however oligoclonal bands turned positive.
Brain biopsy mainly revealed perivascular CD4+ T-cells and demyelinated areas.
Despite ongoing acute meningitis, a 10-day corticosteroid-pulse was initiated
followed by steroid-tapering. Within 4 weeks, clinical and MRI findings
ameliorated. In an one-year follow-up visit, the patient significantly recovered,
MRI lesions were markedly reduced and no further relapses occurred. CONCLUSION:
Acute pneumococcal meningitis in unvaccinated splenectomized patients may be
complicated by a monophasic course of parainfectious ADEM that can be controlled
with high-dose corticosteroids. Parainfectious vasculitis or cerebritis are
important differential diagnoses and exact differentiation of these entities is
important to initiate early appropriate immunotherapy.
PMID- 25140292
TI - The influence of race/ethnicity and place of service on breast reconstruction for
Medicare beneficiaries with mastectomy.
AB - Racial disparities in breast reconstruction for breast cancer are documented.
Place of service has contributed to disparities in cancer care; but the
interaction of race/ethnicity and place of service has not been explicitly
examined. We examined whether place of service modified the effect of
race/ethnicity on receipt of reconstruction. We included women with a mastectomy
for incident breast cancer in SEER-Medicare from 2005-2009. Using Medicare
claims, we determined breast reconstruction within 6 months. Facility
characteristics included: rural/urban location, teaching status, NCI Cancer
Center designation, cooperative oncology group membership, Disproportionate Share
Hospital (DSH) status, and breast surgery volume. Using multivariable logistic
regression, we analyzed reconstruction in relation to minority status and
facility characteristics. Of the 17,958 women, 14.2% were racial/ethnic women of
color and a total of 9.3% had reconstruction. Caucasians disproportionately
received care at non-teaching hospitals (53% v. 42%) and did not at
Disproportionate Share Hospitals (77% v. 86%). Women of color had 55% lower odds
of reconstruction than Caucasians (OR = 0.45; 95% CI 0.37-0.55). Those in lower
median income areas had lower odds of receiving reconstruction, regardless of
race/ethnicity. Odds of reconstruction reduced at rural, non-teaching and
cooperative oncology group hospitals, and lower surgery volume facilities.
Facility effects on odds of reconstruction were similar in analyses stratified by
race/ethnicity status. Race/ethnicity and facility characteristics have
independent effects on utilization of breast reconstruction, with no significant
interaction. This suggests that, regardless of a woman's race/ethnicity, the
place of service influences the likelihood of reconstruction.
PMID- 25140293
TI - Synergistic antitumor effects of S-1 with eribulin in vitro and in vivo for
triple-negative breast cancer cell lines.
AB - Triple-negative breast cancer (TNBC) is associated with a higher incidence of
recurrence and distant metastasis and a poor prognosis, whereas effective
treatment strategies remain to be established. Finding an effective treatment for
TNBC has become imperative. We examined the effect of the combination of S-1 (or
5-FU in an in vitro study) and eribulin in TNBC cell lines. The in vitro effect
of the combination was examined in four TNBC cell lines (MDA-MB-231, MDA-MB-468,
BT-549 and MX-1) using a combination index and isobolograms. In addition, we
assessed the effect of the combination in an MDA-MB-231 tumor xenograft model. A
synergistic effect was observed in three TNBC cell lines (MDA-MB-231, MDA-MB-468,
and MX-1), and in an in vivo study, the combination of S-1 and eribulin resulted
in significantly higher antitumor effects compared with S-1 or eribulin alone. 5
FU induced epithelial-mesenchymal transition (EMT) change in the TNCB cell line,
as supported by the decreased expression of epithelial marker and the increased
expression of mesenchymal markers. Meanwhile, TGF-beta induced EMT changes in a
TNBC cell line and decreased the sensitivity to 5-FU. This result suggests that 5
FU-induced EMT changes reduce the sensitivity to 5-FU. In contrast, eribulin
induced a mesenchymal-epithelial transition (MET) in a TNBC cell line. The EMT
phenotype induced by 5-FU was also canceled by eribulin. We demonstrate that the
combination of S-1 (5-FU) and eribulin exerts a synergistic effect for TNBC cell
lines through MET-induction by eribulin. Therefore, this combination therapy may
be a potential treatment option for TNBC.
PMID- 25140294
TI - Comparison of generalist predators in winter-flooded and conventionally managed
rice paddies and identification of their limiting factors.
AB - Winter-flooding of rice paddies without the application of agricultural chemicals
is attracting attention as a new agricultural method for enhancing the habitat
conditions of wintering waterfowl in rice paddy ecosystems throughout Japan and
east Asia. Conditions in these paddies are expected to result in restoration of
not only the winter habitats of waterfowl but also those of other taxonomic
groups during the rice growing season. In this study, we tested whether the
diversity of summer spiders--ubiquitous predators in rice paddies--was higher in
the winter-flooded paddies than in the conventional ones by conducting field
measurements in 31 winter-flooded and 7 conventional paddies. Limiting factors of
spiders in the winter-flooded paddies were then examined. Results revealed that
both the density and species richness of spiders were significantly higher in the
winter-flooded paddies than in the conventional ones both before and after the
insecticide application against pecky rice bug Stenotus rubrovittatus
(Matsumura)(Hemiptera: Miridae) to conventional paddies. In addition, spider
density and species richness in the winter-flooded paddies correlated with the
availability of two prey groups--chironomids and other nematocera. These findings
suggest that in the winter-flooded paddies the diversity of generalist predators
is higher than in the conventional ones during the rice-growing season and that
the combination of management at both the landscape and field level is likely
more effective for increasing spider abundance in winter-flooded paddies.
PMID- 25140295
TI - Trimodality therapy for bladder preservation in the elderly population with
invasive bladder cancer.
AB - Bladder cancer is considered as primarily a disease of the elderly, typically
aged in their 70s or 80s and often with associated medical comorbidities.
Unfortunately, fewer elderly patients receive radical treatment for muscle
invasive bladder cancer (MIBC) that their younger counterparts. Over the last
decades, several studies have shown that the use of trimodality therapy
consisting of transurethral bladder resection followed by concomitant
chemotherapy and radiation therapy results in comparable outcomes to radical
cystectomy, considered the gold standard for this disease. In this review, we
revised the literature on bladder-preservation treatments using the trimodality
approach in the elderly population with MIBC.
PMID- 25140296
TI - Use of an interactive, faith-based kiosk by congregants of four predominantly,
african-american churches in a metropolitan area.
AB - Chronic diseases are prevalent in ethnic communities. Churches represent a potent
resource for targeted health promotion. A faith-based kiosk was developed as an
informational tool and placed in four predominantly (>80%) African-American
churches. Congregants were surveyed to describe kiosk-use, kiosk-user
characteristics, health status, and self-reported behavior changes attributed to
the kiosk. We analyzed 1,573 questionnaires. Mean age of respondents was 46.4
years and >70% were women. "Older" congregations (mean age >=46.1 years) had more
reports of diabetes (p = 0.002) and heart diseases (p = 0.01) than younger
churches (mean age <=44.1), whereas asthma was more prevalent in the latter (p <
0.001). Prevalence of obesity (40%) was similar across churches (p = 0.570).
Kiosk-use was reported by 420 (26.7%) respondents. Compared to non-users, kiosk
users were >40 years (p < 0.001), and reported >two health conditions, adjusted
Odds Ratio (95% Confidence Interval) = 1.43 (1.0-2.0), p = 0.05. Male kiosk-users
preferred to select disease-specific content, aOR = 1.87 (1.10-3.17), p = 0.02,
while females tended to select information about supportive community resources,
aOR = 0.49 (0.23-1.04), p = 0.062. Knowledge of kiosk-user characteristics and
the "health status" of a congregation, provide an opportunity for targeted,
church-based health promotion.
PMID- 25140297
TI - Self-Medication Practices among a Sample of Latino Migrant Workers in South
Florida.
AB - INTRODUCTION: Although the literature on self-medication among Latino migrant
workers (LMWs) is sparse, a few existing studies indicate that this practice is
common in this community. The purpose of this paper is to estimate health status,
access to health care, and patterns of self-medication practices of a cohort of
LMWs in South Florida. METHODS: A stratified network-based sample was utilized to
recruit 278 LMWs in the Homestead area. After screening for eligibility,
participants were administered a structured questionnaire that collected data on
their health status, access to health care services, and self-medication
practices. A convenience sample of 24 LMWs, who participated in the parent study
were invited back to participate in 3 focus groups to look more in depth into
self-medication practices in the LMW community. RESULTS: Study findings indicate
that LMWs are affected by a vast array of health problems yet lack access to
health care services. Participants already engaged in self-medication practices
in the countries of origin and, upon their arrival in the US, these practices
continue and, in many cases, increase. CONCLUSION: Long-held traditions and lack
of access to the formal health care system in the US contribute to the high
prevalence of self-medication among LMWs. Self-medication practices such as the
use of prescription medications without a prescription and lay injection are high
risk practices that can have harmful consequences. Prevention interventions that
address self-medication in the LMW community are likely to be most effective if
they are culturally adapted to the community and facilitate access to health care
services.
PMID- 25140298
TI - Principals, Agents, and the Intersection between Scientists and Policy-Makers:
Reflections on the H5N1 Controversy.
PMID- 25140299
TI - Dual-use research as a wicked problem.
PMID- 25140300
TI - Absolute quantitation of post-translational modifications.
PMID- 25140301
TI - Compositional Constraint Is the Key Force in Shaping Codon Usage Bias in
Hemagglutinin Gene in H1N1 Subtype of Influenza A Virus.
AB - It is vital to unravel the codon usage bias in order to gain insights into the
evolutionary forces dictating the viral evolution process. Influenza A virus has
attracted attention of many investigators over the years due to high mutation
rate and being cross-specific shift operational in the viral genome. Several
authors have reported that the codon usage bias is low in influenza A viruses,
citing mutational pressure as the decisive force shaping up the codon usage in
these viruses. In this study, complete coding sequences of hemagglutinin genes
for H1N1 subtype of influenza A virus have been explored for the possible codon
usage bias acting upon these genes. The results indicate overall low bias with
peaking ENC values. The GC content is found to be substantially low as against AT
content in the silent codon sites. Significant correlations were observed in
between the compositional parameters versus AT3, implying the possible role of
the latter in shaping codon usage profile in the viral hemagglutinin. The data
showed conspicuously that the sequences were A redundant with most codons
preferring nucleotide A over others in the third synonymous codon site. The
results indicated the pivotal role of compositional pressure affecting codon
usage in this virus.
PMID- 25140303
TI - delta-Tocotrienol oxazine derivative antagonizes mammary tumor cell compensatory
response to CoCl2-induced hypoxia.
AB - In response to low oxygen supply, cancer cells elevate production of HIF-1alpha,
a hypoxia-inducible transcription factor that subsequently acts to stimulate
blood vessel formation and promote survival. Studies were conducted to determine
the role of delta-tocotrienol and a semisynthetic delta-tocotrienol oxazine
derivative, compound 44, on +SA mammary tumor cell hypoxic response. Treatment
with 150 uM CoCl2 induced a hypoxic response in +SA mammary tumor cells as
evidenced by a large increase in HIF-1alpha levels, and combined treatment with
compound 44 attenuated this response. CoCl2-induced hypoxia was also associated
with a large increase in Akt/mTOR signaling, activation of downstream targets
p70S6K and eIF-4E1, and a significant increase in VEGF production, and combined
treatment with compound 44 blocked this response. Additional in vivo studies
showed that intralesional treatment with compound 44 in BALB/c mice bearing +SA
mammary tumors significantly decreased the levels of HIF-1alpha, and this effect
was associated with a corresponding decrease in Akt/mTOR signaling and activation
of downstream targets p70S6 kinase and eIF-4E1. These findings demonstrate that
treatment with the delta-tocotrienol oxazine derivative, compound 44,
significantly attenuates +SA mammary tumor cell compensatory responses to hypoxia
and suggests that this compound may provide benefit in the treatment of rapidly
growing solid breast tumors.
PMID- 25140304
TI - Apocynin, a low molecular oral treatment for neurodegenerative disease.
AB - Accumulating evidence suggests that inflammatory mediators secreted by activated
resident or infiltrated innate immune cells have a significant impact on the
pathogenesis of neurodegenerative diseases. This may imply that patients affected
by a neurodegenerative disease may benefit from treatment with selective
inhibitors of innate immune activity. Here we review the therapeutic potential of
apocynin, an essentially nontoxic phenolic compound isolated from the medicinal
plant Jatropha multifida. Apocynin is a selective inhibitor of the phagocyte
NADPH oxidase Nox2 that can be applied orally and is remarkably effective at low
dose.
PMID- 25140302
TI - The motile breast cancer phenotype roles of proteoglycans/glycosaminoglycans.
AB - The consecutive stages of cancer growth and dissemination are obligatorily
perpetrated through specific interactions of the tumor cells with their
microenvironment. Importantly, cell-associated and tumor microenvironment
glycosaminoglycans (GAGs)/proteoglycan (PG) content and distribution are markedly
altered during tumor pathogenesis and progression. GAGs and PGs perform multiple
functions in specific stages of the metastatic cascade due to their defined
structure and ability to interact with both ligands and receptors regulating
cancer pathogenesis. Thus, GAGs/PGs may modulate downstream signaling of key
cellular mediators including insulin growth factor receptor (IGFR), epidermal
growth factor receptor (EGFR), estrogen receptors (ERs), or Wnt members. In the
present review we will focus on breast cancer motility in correlation with their
GAG/PG content and critically discuss mechanisms involved. Furthermore, new
approaches involving GAGs/PGs as potential prognostic/diagnostic markers or as
therapeutic agents for cancer-related pathologies are being proposed.
PMID- 25140305
TI - The antileukemia activity of natural product HQ17(3) is possibly associated with
downregulation of miR-17-92 cluster.
AB - The compound 10'(Z),13'(E),15'(E)-heptadecatrienylhydroquinone [HQ17(3)] was
purified from the sap of the lacquer tree Rhus succedanea. HQ17(3) has cytotoxic
effect on cancer cells and can inhibit topoisomerase (topo) IIalpha activity. We
treated various cancer cells with different doses of HQ17(3) and found that
leukemia cells were most sensitive to HQ17(3). After analysis of microRNA (miRNA)
profiling, we found that treatment with HQ17(3) caused downregulation of miR-17
92 cluster in some leukemia cells. These changes partially restored the normal
levels from leukemia-specific miRNA expression signature. Messenger RNAs of tumor
suppressor proteins, such as pRB, PTEN, and Dicer, are targets of miR-17-92
cluster. Their protein levels were increased after the treatment. c-Myc is a
regulatory protein for miR-17-92 gene. Similar to topo IIalpha, we found that c
Myc decreased its activity after the HQ17(3) treatment, which may explain the
downregulation of miR-17-92 cluster. Combined with 5-fluorouracil, NaAsO2, or ABT
737, HQ17(3) elicited additive inhibitory effects on leukemia cells. In
conclusion, the high sensitivity of leukemia cells to HQ17(3) may be associated
with the reduction of topo IIalpha and c-Myc activities, as well as with the
downregulation of the miR-17-92 cluster expression.
PMID- 25140307
TI - Angiotensin I-converting enzyme inhibitor derived from cross-linked oyster
protein.
AB - Following cross-linking by microbial transglutaminase, modified oyster proteins
were hydrolyzed to improve inhibitory activity against angiotensin-converting
enzyme (ACE) inhibitory activity with the use of a single protease, or a
combination of six proteases. The oyster hydrolysate with the lowest 50% ACE
inhibitory concentration (IC50) of 0.40 mg/mL was obtained by two-step hydrolysis
of the cross-linked oyster protein using Protamex and Neutrase. Five ACE
inhibitory peptides were purified from the oyster hydrolysate using a multistep
chromatographic procedure comprised of ion-exchange, size exclusion, and reversed
phase liquid chromatography. Their sequences were identified as TAY, VK, KY, FYN,
and YA, using automated Edman degradation and mass spectrometry. These peptides
were synthesized, and their IC50 values were measured to be 16.7, 29.0, 51.5,
68.2, and 93.9 MUM, respectively. Toxicity of the peptides on the HepG2 cell line
was not detected. The oyster hydrolysate also significantly decreased the
systolic blood pressure of spontaneously hypertensive rats (SHR). The
antihypertensive effect of the oyster hydrolysate on SHR was rapid and long
lasting, compared to commercially obtained sardine hydrolysate. These results
suggest that the oyster hydrolysate could be a source of effective nutraceuticals
against hypertension.
PMID- 25140306
TI - The nonglycemic actions of dipeptidyl peptidase-4 inhibitors.
AB - A cell surface serine protease, dipeptidyl peptidase 4 (DPP-4), cleaves dipeptide
from peptides containing proline or alanine in the N-terminal penultimate
position. Two important incretin hormones, glucagon-like peptide-1 (GLP-1) and
glucose-dependent insulinotropic peptide (GIP), enhance meal-stimulated insulin
secretion from pancreatic beta-cells, but are inactivated by DPP-4. Diabetes and
hyperglycemia increase the DPP-4 protein level and enzymatic activity in blood
and tissues. In addition, multiple other functions of DPP-4 suggest that DPP-4
inhibitor, a new class of antidiabetic agents, may have pleiotropic effects.
Studies have shown that DPP-4 itself is involved in the inflammatory signaling
pathway, the stimulation of vascular smooth cell proliferation, and the
stimulation of oxidative stress in various cells. DPP-4 inhibitor ameliorates
these pathophysiologic processes and has been shown to have cardiovascular
protective effects in both in vitro and in vivo experiments. However, in recent
randomized clinical trials, DPP-4 inhibitor therapy in high risk patients with
type 2 diabetes did not show cardiovascular protective effects. Some concerns on
the actions of DPP-4 inhibitor include sympathetic activation and neuropeptide Y
mediated vascular responses. Further studies are required to fully characterize
the cardiovascular effects of DPP-4 inhibitor.
PMID- 25140309
TI - Implementation of incident learning in the safety and quality management of
radiotherapy: the primary experience in a new established program with advanced
technology.
AB - OBJECTIVE: To explore the implementation of incident learning for quality
management of radiotherapy in a new established radiotherapy program. MATERIALS
AND METHODS: With reference to the consensus recommendations by American
Association of Physicist in Medicine, an incident learning system was
specifically established for reporting, investigating, and learning of individual
incidents. The incidents that occurred in external beam radiotherapy from
February, 2012, to February, 2014, were reported. RESULTS: A total of 28 near
misses and 5 incidents were reported. Among them, 5 originated in imaging for
planning, 25 in planning, and 1 in plan transfer, commissioning, and delivery,
respectively. One near miss/incident was classified as wrong patient, 7 wrong
sites, 6 wrong laterality, and 5 wrong dose. Five reported incidents were all
classified as grade 1/2 of dosimetric severity, 1 as grade 0, and the other 4 as
grade 1 of medical severity. For the causes/contributory factors, negligence,
policy not followed, and inadequate training contributed to 19, 15, and 12 near
misses/incidents, respectively. The average incident rate per 100 patients
treated was 0.4. CONCLUSION: Effective implementation of incident learning can
reduce the occurrence of near misses/incidents and enhance the culture of safety.
PMID- 25140308
TI - Progress and prospects in human genetic research into age-related hearing
impairment.
AB - Age-related hearing impairment (ARHI) is a complex, multifactorial disorder that
is attributable to confounding intrinsic and extrinsic factors. The degree of
impairment shows substantial variation between individuals, as is also observed
in the senescence of other functions. This individual variation would seem to
refute the stereotypical view that hearing deterioration with age is inevitable
and may indicate that there is ample scope for preventive intervention. Genetic
predisposition could account for a sizable proportion of interindividual
variation. Over the past decade or so, tremendous progress has been made through
research into the genetics of various forms of hearing impairment, including ARHI
and our knowledge of the complex mechanisms of auditory function has increased
substantially. Here, we give an overview of recent investigations aimed at
identifying the genetic risk factors involved in ARHI and of what we currently
know about its pathophysiology. This review is divided into the following
sections: (i) genes causing monogenic hearing impairment with phenotypic
similarities to ARHI; (ii) genes involved in oxidative stress, biologic stress
responses, and mitochondrial dysfunction; and (iii) candidate genes for
senescence, other geriatric diseases, and neurodegeneration. Progress and
prospects in genetic research are discussed.
PMID- 25140310
TI - Testing for the endogenous nature between women's empowerment and antenatal
health care utilization: evidence from a cross-sectional study in Egypt.
AB - Women's relative lack of decision-making power and their unequal access to
employment, finances, education, basic health care, and other resources are
considered to be the root causes of their ill-health and that of their children.
The main purpose of this paper is to examine the interactive relation between
women's empowerment and the use of maternal health care. Two model specifications
are tested. One assumes no correlation between empowerment and antenatal care
while the second specification allows for correlation. Both the univariate and
the recursive bivariate probit models are tested. The data used in this study is
EDHS 2008. Factor Analysis Technique is also used to construct some of the
explanatory variables such as the availability and quality of health services
indicators. The findings show that women's empowerment and receiving regular
antenatal care are simultaneously determined and the recursive bivariate probit
is a better approximation to the relationship between them. Women's empowerment
has significant and positive impact on receiving regular antenatal care. The
availability and quality of health services do significantly increase the
likelihood of receiving regular antenatal care.
PMID- 25140311
TI - Treatment of bilateral varicocele and other scrotal comorbidities using a single
scrotal access: our experience on 34 patients.
AB - INTRODUCTION: Varicocele is the main cause of infertility in male and the most
correctable cause of it too. In this study, we present our experience on 34
patients affected by bilateral varicocele and other scrotal comorbidities treated
underwent surgery with a scrotal access. MATERIALS AND METHODS: 34 patients were
enrolled with clinical palpable and infraclinical (ultrasonic doppler scanning)
bilateral varicocele and other comorbidities like right hydrocele, left
hydrocele, bilateral hydrocele, and epididymal cyst. They all underwent scrotal
bilateral varicocelectomy under local anesthesia. RESULTS AND DISCUSSION: At 6
months, no other complications were reported. No case of testicular atrophy was
observed. None had recurrence of varicocele. All scrotal comorbidities were
treated as well. CONCLUSION: Scrotal access with local anesthesia is a safe and
useful technique to treat patients with bilateral varicocele and other scrotal
comorbidities.
PMID- 25140312
TI - Effect of prenatal polycyclic aromatic hydrocarbons exposure on birth outcomes:
the Polish mother and child cohort study.
AB - The aim of this study was to assess the impact of PAH exposure on various
anthropometric measures of birth outcomes. The study population consisted of 210
nonsmoking pregnant women. Urine samples collected between 20th and 24th week of
pregnancy were used for analysis of the following PAH metabolites: 1-, 2-, 3-, 4
, and 9-hydroxyphenanthrene (1-, 2-, 3-, 4-, and 9-OH-PHE), 1-hydroxypyrene (1-OH
PYR), 1,6 + 1,8-dihydroxypyrene (DI-OH-PYR), phenanthrene trans-1,2-dihydrodiol
(PHE-1,2-diol), and phenanthrene trans-9,10-dihydrodiol (PHE-9,10-diol) by gas
chromatography-mass spectrometry. Environmental tobacco smoke exposure (ETS) was
assessed by cotinine level in saliva using a stable isotope dilution LC-ESI-MS/MS
method. The mean PAH metabolite concentrations were in the range of 0.15 ug/g
creatinine for 9-OH-PHE to 5.9 ug/g creatinine for PHE-9,10-diol. It was shown
that none of the individual PAH exposure markers demonstrate a statistically
significant influence on birth outcomes. Interestingly a statistically
significant association was found between the sum of OH-PHE along with cotinine
level and the cephalization index after adjusting for potential confounders (P =
0.04). This study provides evidence that combined exposure of pregnant women to
common environmental pollutants such as PAH and ETS might adversely affect fetal
development. Thus, reduction of human exposure to these mixtures of hazardous
compounds would in particular result in substantial health benefits for newborns.
PMID- 25140313
TI - On the coupling of two models of the human immune response to an antigen.
AB - The development of mathematical models of the immune response allows a better
understanding of the multifaceted mechanisms of the defense system. The main
purpose of this work is to present a scheme for coupling distinct models of
different scales and aspects of the immune system. As an example, we propose a
new model where the local tissue inflammation processes are simulated with
partial differential equations (PDEs) whereas a system of ordinary differential
equations (ODEs) is used as a model for the systemic response. The simulation of
distinct scenarios allows the analysis of the dynamics of various immune cells in
the presence of an antigen. Preliminary results of this approach with a
sensitivity analysis of the coupled model are shown but further validation is
still required.
PMID- 25140314
TI - Speech understanding with a new implant technology: a comparative study with a
new nonskin penetrating Baha system.
AB - OBJECTIVE: To compare hearing and speech understanding between a new, nonskin
penetrating Baha system (Baha Attract) to the current Baha system using a skin
penetrating abutment. METHODS: Hearing and speech understanding were measured in
16 experienced Baha users. The transmission path via the abutment was compared to
a simulated Baha Attract transmission path by attaching the implantable magnet to
the abutment and then by adding a sample of artificial skin and the external
parts of the Baha Attract system. Four different measurements were performed:
bone conduction thresholds directly through the sound processor (BC Direct),
aided sound field thresholds, aided speech understanding in quiet, and aided
speech understanding in noise. RESULTS: The simulated Baha Attract transmission
path introduced an attenuation starting from approximately 5 dB at 1000 Hz,
increasing to 20-25 dB above 6000 Hz. However, aided sound field threshold shows
smaller differences and aided speech understanding in quiet and in noise does not
differ significantly between the two transmission paths. CONCLUSION: The Baha
Attract system transmission path introduces predominately high frequency
attenuation. This attenuation can be partially compensated by adequate fitting of
the speech processor. No significant decrease in speech understanding in either
quiet or in noise was found.
PMID- 25140316
TI - Intracochlear fluid pressure changes related to the insertional speed of a CI
electrode.
AB - INTRODUCTION: To preserve residual hearing the atraumaticity of the cochlea
electrode insertion has become a focus of cochlear implant research. In addition
to other factors, the speed of insertion is thought to be a contributing factor
in the concept of atraumatic implantation. The aim of our study was to observe
intracochlear fluid pressure changes due to different insertional speeds of an
implant electrode in a cochlear model. MATERIALS AND METHODS: The experiments
were performed using an artificial cochlear model. A linear actuator was mounted
on an Advanced Bionics IJ insertional tool. The intracochlear fluid pressure was
recorded through a pressure sensor which was placed in the helicotrema area.
Defined insertions were randomly performed with speeds of 0.1 mm/sec, 0.25
mm/sec, 0.5 mm/sec, 1 mm/sec, and 2 mm/sec. RESULTS: A direct correlation between
speed and pressure was observed. Mean maximum values of intracochlear fluid
pressure varied between 0.41 mm Hg and 1.27 mm Hg. Conclusion. We provide the
first results of fluid pressure changes due to insertional speeds of CI
electrodes in a cochlear model. A relationship between the insertional speed and
intracochlear fluid pressure was observed. Further experiments are needed to
apply these results to the in vivo situation.
PMID- 25140317
TI - Mesenchymal stem cell-induced doxorubicin resistance in triple negative breast
cancer.
AB - Triple negative breast cancer (TNBC) is an aggressive histological subtype with
limited treatment options and a worse clinical outcome compared with other breast
cancer subtypes. Doxorubicin is considered to be one of the most effective agents
in the treatment of TNBC. Unfortunately, resistance to this agent is common. In
some drug-resistant cells, drug efflux is mediated by adenosine triphosphate
dependent membrane transporter termed adenosine triphosphate-binding cassette
(ABC) transporter, which can drive the substrates across membranes against
concentration gradient. In the tumor microenvironment, upon interaction with
mesenchymal stem cells (MSCs), tumor cells exhibit altered biological functions
of certain gene clusters, hence increasing stemness of tumor cells, migration
ability, angiogenesis, and drug resistance. In our present study, we investigated
the mechanism of TNBC drug resistance induced by adipose-derived MSCs. Upon
exposure of TNBC to MSC-secreted conditioned medium (CM), noticeable drug
resistance against doxorubicin with markedly increased BCRP protein expression
was observed. Intracellular doxorubicin accumulation of TNBC was also decreased
by MSC-secreted CM. Furthermore, we found that doxorubicin resistance of TNBC was
mediated by IL-8 presented in the MSC-secreted CM. These findings may enrich the
list of potential targets for overcoming drug resistance induced by MSCs in TNBC
patients.
PMID- 25140318
TI - An efficient parallel algorithm for multiple sequence similarities calculation
using a low complexity method.
AB - With the advance of genomic researches, the number of sequences involved in
comparative methods has grown immensely. Among them, there are methods for
similarities calculation, which are used by many bioinformatics applications. Due
the huge amount of data, the union of low complexity methods with the use of
parallel computing is becoming desirable. The k-mers counting is a very efficient
method with good biological results. In this work, the development of a parallel
algorithm for multiple sequence similarities calculation using the k-mers
counting method is proposed. Tests show that the algorithm presents a very good
scalability and a nearly linear speedup. For 14 nodes was obtained 12x speedup.
This algorithm can be used in the parallelization of some multiple sequence
alignment tools, such as MAFFT and MUSCLE.
PMID- 25140319
TI - Informative gene selection and direct classification of tumor based on Chi-square
test of pairwise gene interactions.
AB - In efforts to discover disease mechanisms and improve clinical diagnosis of
tumors, it is useful to mine profiles for informative genes with definite
biological meanings and to build robust classifiers with high precision. In this
study, we developed a new method for tumor-gene selection, the Chi-square test
based integrated rank gene and direct classifier (chi(2)-IRG-DC). First, we
obtained the weighted integrated rank of gene importance from chi-square tests of
single and pairwise gene interactions. Then, we sequentially introduced the
ranked genes and removed redundant genes by using leave-one-out cross-validation
of the chi-square test-based Direct Classifier (chi(2)-DC) within the training
set to obtain informative genes. Finally, we determined the accuracy of
independent test data by utilizing the genes obtained above with chi(2)-DC.
Furthermore, we analyzed the robustness of chi(2)-IRG-DC by comparing the
generalization performance of different models, the efficiency of different
feature-selection methods, and the accuracy of different classifiers. An
independent test of ten multiclass tumor gene-expression datasets showed that
chi(2)-IRG-DC could efficiently control overfitting and had higher generalization
performance. The informative genes selected by chi(2)-IRG-DC could dramatically
improve the independent test precision of other classifiers; meanwhile, the
informative genes selected by other feature selection methods also had good
performance in chi(2)-DC.
PMID- 25140315
TI - Autophagy in alcohol-induced multiorgan injury: mechanisms and potential
therapeutic targets.
AB - Autophagy is a genetically programmed, evolutionarily conserved intracellular
degradation pathway involved in the trafficking of long-lived proteins and
cellular organelles to the lysosome for degradation to maintain cellular
homeostasis. Alcohol consumption leads to injury in various tissues and organs
including liver, pancreas, heart, brain, and muscle. Emerging evidence suggests
that autophagy is involved in alcohol-induced tissue injury. Autophagy serves as
a cellular protective mechanism against alcohol-induced tissue injury in most
tissues but could be detrimental in heart and muscle. This review summarizes
current knowledge about the role of autophagy in alcohol-induced injury in
different tissues/organs and its potential molecular mechanisms as well as
possible therapeutic targets based on modulation of autophagy.
PMID- 25140320
TI - Ablative therapy for esophageal dysplasia and early malignancy: focus on RFA.
AB - Ablative therapies have been utilized with increasing frequency for the treatment
of Barrett's esophagus with and without dysplasia. Multiple modalities are
available for topical ablation of the esophagus, but radiofrequency ablation
(RFA) remains the most commonly used. There have been significant advances in
technique since the introduction of RFA. The aim of this paper is to review the
indications, techniques, outcomes, and most common complications following
esophageal ablation with RFA.
PMID- 25140321
TI - Screening of cognitive function and hearing impairment in older adults: a
preliminary study.
AB - BACKGROUND: Previous research has found that hearing loss is associated with
poorer cognitive function. The question is that when a hearing impairment is
being compensated for by appropriately fitted monaural hearing aids, special
precautions are still needed when screening cognitive function in older adults.
OBJECTIVE: This research examined cognitive function in elderly hearing aid users
who used monaural hearing aids and whether the presence of a hearing impairment
should be accounted for when screening cognitive function in these individuals.
METHODS: Auditory thresholds, sentence reception thresholds, and self-reported
outcomes with hearing aids were measured in 34 older hearing aid users to ensure
hearing aids were appropriately fitted. Mini-Mental State Examination (MMSE)
results obtained in these participants were then compared to normative data
obtained in a general older population exhibiting similar demographic
characteristics. Stepwise multiple regression analyses were used to examine the
effects of demographic and auditory variables on MMSE scores. CONCLUSIONS:
Results showed that, even with appropriately fitted hearing aids, cognitive
decline was significant. Besides the factors commonly measured in the literature,
we believed that auditory deprivation was not being fully compensated for by
hearing aids. Most importantly, screening of cognitive function should take into
account the effects of hearing impairment, even when hearing devices have been
appropriately fitted.
PMID- 25140323
TI - Cytoskeleton modifications and autophagy induction in TCam-2 seminoma cells
exposed to simulated microgravity.
AB - The study of how mechanical forces may influence cell behavior via cytoskeleton
remodeling is a relevant challenge of nowadays that may allow us to define the
relationship between mechanics and biochemistry and to address the larger problem
of biological complexity. An increasing amount of literature data reported that
microgravity condition alters cell architecture as a consequence of cytoskeleton
structure modifications. Herein, we are reporting the morphological,
cytoskeletal, and behavioral modifications due to the exposition of a seminoma
cell line (TCam-2) to simulated microgravity. Even if no differences in cell
proliferation and apoptosis were observed after 24 hours of exposure to simulated
microgravity, scanning electron microscopy (SEM) analysis revealed that the
change of gravity vector significantly affects TCam-2 cell surface morphological
appearance. Consistent with this observation, we found that microtubule
orientation is altered by microgravity. Moreover, the confocal analysis of actin
microfilaments revealed an increase in the cell width induced by the low
gravitational force. Microtubules and microfilaments have been related to
autophagy modulation and, interestingly, we found a significant autophagic
induction in TCam-2 cells exposed to simulated microgravity. This observation is
of relevant interest because it shows, for the first time, TCam-2 cell autophagy
as a biological response induced by a mechanical stimulus instead of a
biochemical one.
PMID- 25140324
TI - Role of CT perfusion in monitoring and prediction of response to therapy of head
and neck squamous cell carcinoma.
AB - This review aims to summarize the technique and clinical applications of CT
perfusion (CTp) of head and neck cancer. The most common pathologic type (90%) of
head and neck cancer is squamous cell carcinoma (HNSCC): its diagnostic workup
relies on CT and MRI, as they provide an accurate staging for the disease by
determining tumour volume, assessing its extension, and detecting of lymph node
metastases. Compared with conventional CT and MRI, CTp allows for obtaining
measures of tumour vascular physiology and functional behaviour, and it has been
demonstrated to be a feasible and useful tool in predicting local outcomes in
patients undergoing radiation therapy and chemotherapy and may help monitor both
treatments.
PMID- 25140322
TI - Alpha-melanocyte stimulating hormone: an emerging anti-inflammatory antimicrobial
peptide.
AB - The alpha-melanocyte stimulating hormone (alpha-MSH) is a neuropeptide belonging
to the melanocortin family. It is well known for its anti-inflammatory and
antipyretic effects and shares several characteristics with antimicrobial
peptides (AMPs). There have been some recent reports about the direct
antimicrobial activity of alpha-MSH against various microbes belonging to both
fungal and bacterial pathogens. Similar to alpha-MSH's anti-inflammatory
properties, its C-terminal residues also exhibit antimicrobial activity parallel
to that of the entire peptide. This review is focused on the current findings
regarding the direct antimicrobial potential and immunomodulatory mechanism of
alpha-MSH and its C-terminal fragments, with particular emphasis on the prospects
of alpha-MSH based peptides as a strong anti-infective agent.
PMID- 25140326
TI - Innovations in pancreatic surgery.
PMID- 25140325
TI - Prevention and restoration of hearing loss associated with the use of cisplatin.
AB - BACKGROUND: Cisplatin is a well known platinum-based chemotherapeutic agent used
for the treatment of various malignant tumours. A frequent side effect of
cisplatin therapy is ototoxicity. Unfortunately, currently there are no available
treatments. MATERIAL AND METHODS: Experimental, clinical studies and reviews
published between 2004 and 2014 in the English medical literature concerning
ototoxicity were selected using Medline, PubMed, and Google Scholar databases.
Inclusion criteria were cisplatin-induced ototoxicity and therapy aimed at
preventing or curing this disorder. Molecular mechanisms and clinical,
audiological, and histological markers of cisplatin-induced ototoxicity are
described. Moreover, experimental and clinical strategies for prevention or
treatment of hearing loss were also reviewed. RESULTS AND DISCUSSION:
Experimental studies demonstrate a wide range of otoprotective molecules and
strategies efficient against cisplatin-induced hearing loss. However, only
dexamethasone proved a slight otoprotective effect in a clinical study.
CONCLUSION: Further research must be completed to bring future therapeutic
options into clinical setting.
PMID- 25140328
TI - Modeling and optimization of multiple unmanned aerial vehicles system
architecture alternatives.
AB - Unmanned aerial vehicle (UAV) systems have already been used in civilian
activities, although very limitedly. Confronted different types of tasks, multi
UAVs usually need to be coordinated. This can be extracted as a multi UAVs system
architecture problem. Based on the general system architecture problem, a
specific description of the multi UAVs system architecture problem is presented.
Then the corresponding optimization problem and an efficient genetic algorithm
with a refined crossover operator (GA-RX) is proposed to accomplish the
architecting process iteratively in the rest of this paper. The availability and
effectiveness of overall method is validated using 2 simulations based on 2
different scenarios.
PMID- 25140327
TI - Airborne biogenic particles in the snow of the cities of the Russian Far East as
potential allergic compounds.
AB - This paper presents an analysis of airborne biogenic particles (1 mkm-1 mm) found
in the snow in several cities of the Russian Far East during 2010-2013. The most
common was vegetational terraneous detritus (fragments of tree and grass leaves)
followed by animal hair, small insects and their fragments, microorganisms of
aeroplankton, and equivocal biological garbage. Specific components were found in
samples from locations close to bodies of water such as fragments of algae and
mollusc shells and, marine invertebrates (needles of sea urchins and shell debris
of arthropods). In most locations across the Far East (Vladivostok, Khabarovsk,
Blagoveshchensk, and Ussuriysk), the content of biogenic particles collected in
the winter did not exceed 10% of the total particulate matter, with the exception
of Birobidzhan and the nature reserve Bastak, where it made up to 20%. Most of
all biogenic compounds should be allergic: hair, fragments of tree and grass
leaves, insects, and microorganisms.
PMID- 25140329
TI - The effects of rape residue mulching on net global warming potential and
greenhouse gas intensity from no-tillage paddy fields.
AB - A field experiment was conducted to provide a complete greenhouse gas (GHG)
accounting for global warming potential (GWP), net GWP, and greenhouse gas
intensity (GHGI) from no-tillage (NT) paddy fields with different amounts of
oilseed rape residue mulch (0, 3000, 4000, and 6000 kg dry matter (DM) ha(-1))
during a rice-growing season after 3 years of oilseed rape-rice cultivation.
Residue mulching treatments showed significantly more organic carbon (C) density
for the 0-20 cm soil layer at harvesting than no residue treatment. During a rice
growing season, residue mulching treatments sequestered significantly more
organic C from 687 kg C ha(-1) season(-1) to 1654 kg C ha(-1) season(-1) than no
residue treatment. Residue mulching significantly increased emissions of CO2 and
N2O but decreased CH4 emissions. Residue mulching treatments significantly
increased GWP by 9-30% but significantly decreased net GWP by 33-71% and GHGI by
35-72% relative to no residue treatment. These results suggest that agricultural
economic viability and GHG mitigation can be achieved simultaneously by residue
mulching on NT paddy fields in central China.
PMID- 25140330
TI - A new graph-based molecular descriptor using the canonical representation of the
molecule.
AB - Molecular similarity is a pervasive concept in drug design. The basic idea
underlying molecular similarity is the similar property principle, which states
that structurally similar molecules will exhibit similar physicochemical and
biological properties. In this paper, a new graph-based molecular descriptor
(GBMD) is introduced. The GBMD is a new method of obtaining a rough description
of 2D molecular structure in textual form based on the canonical representations
of the molecule outline shape and it allows rigorous structure specification
using small and natural grammars. Simulated virtual screening experiments with
the MDDR database show clearly the superiority of the graph-based descriptor
compared to many standard descriptors (ALOGP, MACCS, EPFP4, CDKFP, PCFP, and
SMILE) using the Tanimoto coefficient (TAN) and the basic local alignment search
tool (BLAST) when searches were carried.
PMID- 25140331
TI - A novel deployment method for communication-intensive applications in service
clouds.
AB - The service platforms are migrating to clouds for reasonably solving long
construction periods, low resource utilizations, and isolated constructions of
service platforms. However, when the migration is conducted in service clouds,
there is a little focus of deploying communication-intensive applications in
previous deployment methods. To address this problem, this paper proposed the
combination of the online deployment and the offline deployment for deploying
communication-intensive applications in service clouds. Firstly, the system
architecture was designed for implementing the communication-aware deployment
method for communication-intensive applications in service clouds. Secondly, in
the online-deployment algorithm and the offline-deployment algorithm, service
instances were deployed in an optimal cloud node based on the communication
overhead which is determined by the communication traffic between services, as
well as the communication performance between cloud nodes. Finally, the
experimental results demonstrated that the proposed methods deployed
communication-intensive applications effectively with lower latency and lower
load compared with existing algorithms.
PMID- 25140332
TI - A review of subsequence time series clustering.
AB - Clustering of subsequence time series remains an open issue in time series
clustering. Subsequence time series clustering is used in different fields, such
as e-commerce, outlier detection, speech recognition, biological systems, DNA
recognition, and text mining. One of the useful fields in the domain of
subsequence time series clustering is pattern recognition. To improve this field,
a sequence of time series data is used. This paper reviews some definitions and
backgrounds related to subsequence time series clustering. The categorization of
the literature reviews is divided into three groups: preproof, interproof, and
postproof period. Moreover, various state-of-the-art approaches in performing
subsequence time series clustering are discussed under each of the following
categories. The strengths and weaknesses of the employed methods are evaluated as
potential issues for future studies.
PMID- 25140333
TI - An improved multidimensional MPA procedure for bidirectional earthquake
excitations.
AB - Presently, the modal pushover analysis procedure is extended to multidimensional
analysis of structures subjected to multidimensional earthquake excitations. an
improved multidimensional modal pushover analysis (IMMPA) method is presented in
the paper in order to estimate the response demands of structures subjected to
bidirectional earthquake excitations, in which the unidirectional earthquake
excitation applied on equivalent SDOF system is replaced by the direct
superposition of two components earthquake excitations, and independent analysis
in each direction is not required and the application of simplified superposition
formulas is avoided. The strength reduction factor spectra based on superposition
of earthquake excitations are discussed and compared with the traditional
strength reduction factor spectra. The step-by-step procedure is proposed to
estimate seismic demands of structures. Two examples are implemented to verify
the accuracy of the method, and the results of the examples show that (1) the
IMMPA method can be used to estimate the responses of structure subjected to
bidirectional earthquake excitations. (2) Along with increase of peak of
earthquake acceleration, structural response deviation estimated with the IMMPA
method may also increase. (3) Along with increase of the number of total floors
of structures, structural response deviation estimated with the IMMPA method may
also increase.
PMID- 25140334
TI - Nonlinear secret image sharing scheme.
AB - Over the past decade, most of secret image sharing schemes have been proposed by
using Shamir's technique. It is based on a linear combination polynomial
arithmetic. Although Shamir's technique based secret image sharing schemes are
efficient and scalable for various environments, there exists a security threat
such as Tompa-Woll attack. Renvall and Ding proposed a new secret sharing
technique based on nonlinear combination polynomial arithmetic in order to solve
this threat. It is hard to apply to the secret image sharing. In this paper, we
propose a (t, n)-threshold nonlinear secret image sharing scheme with
steganography concept. In order to achieve a suitable and secure secret image
sharing scheme, we adapt a modified LSB embedding technique with XOR Boolean
algebra operation, define a new variable m, and change a range of prime p in
sharing procedure. In order to evaluate efficiency and security of proposed
scheme, we use the embedding capacity and PSNR. As a result of it, average value
of PSNR and embedding capacity are 44.78 (dB) and 1.74t?log2 m? bit-per-pixel
(bpp), respectively.
PMID- 25140336
TI - Compressive strength, chloride permeability, and freeze-thaw resistance of MWNT
concretes under different chemical treatments.
AB - This study investigated compressive strength, chloride penetration, and freeze
thaw resistance of multiwalled carbon nanotube (MWNT) concrete. More than 100
cylindrical specimens were used to assess test variables during sensitivity
observations, including water-cement ratios (0.75, 0.5, and 0.4) and exposure to
chemical agents (including gum arabic, propanol, ethanol, sodium polyacrylate,
methylcellulose, sodium dodecyl sulfate, and silane). To determine the adequate
sonication time for MWNT dispersal in water, the compressive strengths of MWNT
concrete cylinders were measured after sonication times ranging from 2 to 24
minutes. The results demonstrated that the addition of MWNT can increase the
compressive strength of concrete by up to 108%. However, without chemical
treatment, MWNT concretes tend to have poor freeze-thaw resistance. Among the
different chemical treatments, MWNT concrete treated with sodium polyacrylate has
the best compressive strength, chloride resistance, and freeze-thaw durability.
PMID- 25140335
TI - HPLC-fingerprints and antioxidant constituents of Phyla nodiflora.
AB - Phyla nodiflora is a creeping perennial herb, widely distributed in the most
tropical and subtropical regions. It has been used as a folk medicine, herbal
beverage, or folk cosmetic. For these usages, the development of a chemical
quality control method of this plant is necessary. In the present study, ten
compounds, namely, 3,7,4',5'-tetrahydroxy-3'-methoxyflavone (1), nodifloretin
(2), 4'-hydroxywogonin (3), onopordin (4), cirsiliol (5), 5,7,8,4'-tetrahydroxy
3'-methoxyflavone (6), eupafolin (7), hispidulin (8), larycitrin (9), and beta
sitosterol were isolated from the methanolic extract of the aerial part of P.
nodiflora (PNM) and their structures were identified by 1D-NMR comparing their
spectra with the literature. The antioxidant activities of these compounds were
evaluated by free radical scavenging activity and tyrosinase inhibitory effect in
cell-free systems. Compounds 4, 5, and 7 showed strong antioxidant activity. To
control the quality of P. nodiflora, a simple and reliable method of high
performance liquid chromatography combined with ultraviolet detector (HPLC-UV)
was established for both the fingerprint analysis and the quantitative
determination of two selected active compounds, onopordin (4) and eupafolin (7).
Statistical analysis of the obtained data demonstrated that our method achieved
the desired linearity, precision, and accuracy. The results indicated that the
developed method can be used as a quality evaluation method for PNM.
PMID- 25140338
TI - Hesitant triangular fuzzy information aggregation operators based on Bonferroni
means and their application to multiple attribute decision making.
AB - We investigate the multiple attribute decision-making (MADM) problems with
hesitant triangular fuzzy information. Firstly, definition and some operational
laws of hesitant triangular fuzzy elements are introduced. Then, we develop some
hesitant triangular fuzzy aggregation operators based on Bonferroni means and
discuss their basic properties. Some existing operators can be viewed as their
special cases. Next, we apply the proposed operators to deal with multiple
attribute decision-making problems under hesitant triangular fuzzy environment.
Finally, an illustrative example is given to show the developed method and
demonstrate its practicality and effectiveness.
PMID- 25140337
TI - Tunneling and suture of thoracic epidural catheters decrease the incidence of
catheter dislodgement.
AB - BACKGROUND: Dislocation of epidural catheters (EC) is associated with early
termination of regional analgesia and rare complications like epidural bleeding.
We tested the hypothesis that maximum effort in fixation by tunneling and suture
decreases the incidence of catheter dislocation. METHODS: Patients scheduled for
major surgery (n = 121) were prospectively randomized in 2 groups. Thoracic EC
were subcutaneously tunneled and sutured (tunneled) or fixed with adhesive tape
(taped). The difference of EC length at skin surface level immediately after
insertion and before removal was determined and the absolute values were
averaged. Postoperative pain was evaluated by numeric rating scale twice daily
and EC tips were screened microbiologically after removal. RESULTS: Both groups
did not differ with respect to treatment duration (tunneled: 109 hours +/- 46,
taped: 97 +/- 37) and postoperative pain scores. Tunneling significantly reduced
average extent (tunneled: 3 mm +/- 7, taped: 10 +/- 18) and incidence of
clinically relevant EC dislocation (>20 mm, tunneled: 1/60, taped: 9/61).
Bacterial contamination showed a tendency to be lower in patients with tunneled
catheters (8/59, taped: 14/54, P = 0.08). CONCLUSION: Thorough fixation of EC by
tunneling and suturing decreases the incidence and extent of dislocation and
potentially even that of bacterial contamination.
PMID- 25140339
TI - MAC protocol for ad hoc networks using a genetic algorithm.
AB - The problem of obtaining the transmission rate in an ad hoc network consists in
adjusting the power of each node to ensure the signal to interference ratio (SIR)
and the energy required to transmit from one node to another is obtained at the
same time. Therefore, an optimal transmission rate for each node in a medium
access control (MAC) protocol based on CSMA-CDMA (carrier sense multiple access
code division multiple access) for ad hoc networks can be obtained using
evolutionary optimization. This work proposes a genetic algorithm for the
transmission rate election considering a perfect power control, and our
proposition achieves improvement of 10% compared with the scheme that handles the
handshaking phase to adjust the transmission rate. Furthermore, this paper
proposes a genetic algorithm that solves the problem of power combining,
interference, data rate, and energy ensuring the signal to interference ratio in
an ad hoc network. The result of the proposed genetic algorithm has a better
performance (15%) compared to the CSMA-CDMA protocol without optimizing.
Therefore, we show by simulation the effectiveness of the proposed protocol in
terms of the throughput.
PMID- 25140340
TI - Performance analysis of single-frequency MPPSK integrated system for ranging
applications.
AB - The dual-frequency MPPSK-MODEM is a flexible platform. When ranging accuracy
request is low or platform is particularly limited by power, the platform would
perform both data transmission and range measurement with single-frequency modes.
In this paper, the ranging resolution of MPPSK pulse waveforms with the match
filter and impacting filter processing are discussed, respectively. Also, the
parameter selection of MPPSK modulator for ranging is considered. In particular,
requirements that allow for employing such special parameter values for range
measurements with high accuracy and high range are investigated. Moreover, high
repetition frequency (HRF) biphase code MPPSK pulse train base on m sequence is
presented, and the ranging accuracy of the proposed signal with the match filter
processing is deduced. In addition to theoretical considerations, the paper
presents system simulations and measurement results of single-frequency MPPSK
integrated systems, demonstrating the high-performance of ranging applications.
PMID- 25140342
TI - Integrated system of structural health monitoring and intelligent management for
a cable-stayed bridge.
AB - It is essential to construct structural health monitoring systems for large
important bridges. Zhijiang Bridge is a cable-stayed bridge that was built
recently over the Hangzhou Qiantang River (the largest river in Zhejiang
Province). The length of Zhijiang Bridge is 478 m, which comprises an arched twin
tower space and a twin-cable plane structure. As an example, the present study
describes the integrated system of structural health monitoring and intelligent
management for Zhijiang Bridge, which comprises an information acquisition
system, data management system, evaluation and decision-making system, and
application service system. The monitoring components include the working
environment of the bridge and various factors that affect bridge safety, such as
the stress and strain of the main bridge structure, vibration, cable force,
temperature, and wind speed. In addition, the integrated system includes a
forecasting and decision-making module for real-time online evaluation, which
provides warnings and makes decisions based on the monitoring information. From
this, the monitoring information, evaluation results, maintenance decisions, and
warning information can be input simultaneously into the bridge monitoring center
and traffic emergency center to share the monitoring data, thereby facilitating
evaluations and decision making using the system.
PMID- 25140341
TI - Extract of Antrodia camphorata exerts neuroprotection against embolic stroke in
rats without causing the risk of hemorrhagic incidence.
AB - In this study, the neuroprotective effect of an extract of Antrodia camphorata
(A. camphorata), a fungus commonly used in Chinese folk medicine for treatment of
viral hepatitis and cancer, alone or in combination with aspirin was investigated
in a rat embolic stroke model. An ischemic stroke was induced in rats by a
selective occlusion of the middle cerebral artery (MCA) with whole blood clots
and then orally treated with A. camphorata (0.25 and 0.75 g/kg/day) alone and
combined with aspirin (5 mg/kg/day). Sixty days later, the brains were removed,
sectioned, and stained with triphenyltetrazolium chloride and analysed by a
commercial image processing software program. Brain infarct volume,
neurobehavioral score, cerebral blood perfusion, and subarachnoid and
intracerebral hemorrhage incidence were perceived. In addition, potential
bleeding side effect of the combinative therapy was assessed by measuring
hemoglobin (Hb) content during intracerebral hemorrhage and gastric bleeding,
prothrombin time (PT), and occlusion time (OT) after oral administration.
Posttreatment with high dose A. camphorata significantly reduced infarct volume
and improved neurobehavioral score (P < 0.05). Since A. camphorata alone or with
aspirin did not alter the Hb level, this treatment is safe and does not cause
hemorrhagic incident. Remarkably, the combination of A. camphorata and aspirin
did not show a significant effect on the bleeding time, PT and OT increase
suggesting that A. camphorata may have the neuroprotective effect without the
prolongation of bleeding time or coagulation time. From these observations, we
suggest that combinative therapy of A. camphorata and aspirin might offer
enhanced neuroprotective efficacies without increasing side effects.
PMID- 25140343
TI - Application of empirical mode decomposition with local linear quantile regression
in financial time series forecasting.
AB - This paper mainly forecasts the daily closing price of stock markets. We propose
a two-stage technique that combines the empirical mode decomposition (EMD) with
nonparametric methods of local linear quantile (LLQ). We use the proposed
technique, EMD-LLQ, to forecast two stock index time series. Detailed experiments
are implemented for the proposed method, in which EMD-LPQ, EMD, and Holt-Winter
methods are compared. The proposed EMD-LPQ model is determined to be superior to
the EMD and Holt-Winter methods in predicting the stock closing prices.
PMID- 25140345
TI - Displacement back analysis for a high slope of the Dagangshan Hydroelectric Power
Station based on BP neural network and particle swarm optimization.
AB - The right bank high slope of the Dagangshan Hydroelectric Power Station is
located in complicated geological conditions with deep fractures and unloading
cracks. How to obtain the mechanical parameters and then evaluate the safety of
the slope are the key problems. This paper presented a displacement back analysis
for the slope using an artificial neural network model (ANN) and particle swarm
optimization model (PSO). A numerical model was established to simulate the
displacement increment results, acquiring training data for the artificial neural
network model. The backpropagation ANN model was used to establish a mapping
function between the mechanical parameters and the monitoring displacements. The
PSO model was applied to initialize the weights and thresholds of the
backpropagation (BP) network model and determine suitable values of the
mechanical parameters. Then the elastic moduli of the rock masses were obtained
according to the monitoring displacement data at different excavation stages, and
the BP neural network model was proved to be valid by comparing the measured
displacements, the displacements predicted by the BP neural network model, and
the numerical simulation using the back-analyzed parameters. The proposed model
is useful for rock mechanical parameters determination and instability
investigation of rock slopes.
PMID- 25140344
TI - Management of mango hopper, Idioscopus clypealis, using chemical insecticides and
Neem oil.
AB - An experiment was conducted in Field Laboratory, Department of Entomology at
Bangladesh Agricultural University, Mymensingh, during 2013 to manage the mango
hopper, Idioscopus clypealis L, using three chemical insecticides, Imidacloprid
(0.3%), Endosulfan (0.5%), and Cypermethrin (0.4%), and natural Neem oil (3%)
with three replications of each. All the treatments were significantly effective
in managing mango hopper in comparison to the control. Imidacloprid showed the
highest efficacy in percentage of reduction of hopper population (92.50 +/- 9.02)
at 72 hours after treatment in case of 2nd spray. It also showed the highest
overall percentage of reduction (88.59 +/- 8.64) of hopper population and less
toxicity to natural enemies including green ant, spider, and lacewing of mango
hopper. In case of biopesticide, azadirachtin based Neem oil was found effective
against mango hopper as 48.35, 60.15, and 56.54% reduction after 24, 72, and 168
hours of spraying, respectively, which was comparable with Cypermethrin as there
was no statistically significant difference after 168 hours of spray. Natural
enemies were also higher after 1st and 2nd spray in case of Neem oil.
PMID- 25140346
TI - CUDT: a CUDA based decision tree algorithm.
AB - Decision tree is one of the famous classification methods in data mining. Many
researches have been proposed, which were focusing on improving the performance
of decision tree. However, those algorithms are developed and run on traditional
distributed systems. Obviously the latency could not be improved while processing
huge data generated by ubiquitous sensing node in the era without new technology
help. In order to improve data processing latency in huge data mining, in this
paper, we design and implement a new parallelized decision tree algorithm on a
CUDA (compute unified device architecture), which is a GPGPU solution provided by
NVIDIA. In the proposed system, CPU is responsible for flow control while the GPU
is responsible for computation. We have conducted many experiments to evaluate
system performance of CUDT and made a comparison with traditional CPU version.
The results show that CUDT is 5 ~ 55 times faster than Weka-j48 and is 18 times
speedup than SPRINT for large data set.
PMID- 25140347
TI - Characterization of the complete nuclear ribosomal DNA sequences of
Paramphistomum cervi.
AB - Sequences of the complete nuclear ribosomal DNA (rDNA) gene from five individual
Paramphistomum cervi were determined for the first time. The five complete rDNA
sequences, which included the 18S rDNA, the internal transcribed spacer 1 (ITS1),
the 5.8S rDNA, the internal transcribed spacer 2 (ITS2), the 28S rDNA, and the
intergenic spacer (IGS) regions, had a length range of 8,493-10,221 bp. The
lengths of the investigated 18S, ITS1, 5.8S, ITS2, and 28S rDNA sequences, which
were 1,994 bp, 1,293 bp, 157 bp, 286 bp, and 4,186 bp, respectively, did not
vary. However, the IGS rDNA sequences had a length range of 577-2,305 bp. The
5.8S and ITS-2 rDNA sequences had 100% identity among the five investigated
samples, while the identities among the IGS had a range of 53.7-99.8%. A
comparative analysis revealed that different types and numbers of repeats were
found within each ITS1 and IGS region, which may be related to the length
polymorphism of IGS. The phylogenetic position of P. cervi in Paramphistomatidae
was analyzed based on the 18S rDNA sequences. These results will aid in studying
the intra- and interspecific variation of the Paramphistomatidae and the
systematics and phylogenetics of Digenea.
PMID- 25140348
TI - Effects of salt-drought stress on growth and physiobiochemical characteristics of
Tamarix chinensis seedlings.
AB - The present study was designed to clarify the effects of salinity and water
intercross stresses on the growth and physiobiochemical characteristics of
Tamarix chinensis seedlings by pots culture under the artificial simulated
conditions. The growth, activities of SOD, POD, and contents of MDA and osmotic
adjusting substances of three years old seedlings of T. chinensis were studied
under different salt-drought intercross stress. Results showed that the influence
of salt stress on growth was greater than drought stress, the oxidation
resistance of SOD and POD weakened gradually with salt and drought stresses
intensified, and the content of MDA was higher under severe drought and mild and
moderate salt stresses. The proline contents increased with the stress
intensified but only significantly higher than control under the intercross
stresses of severe salt-severe drought. It implied that T. chinensis could
improve its stress resistance by adjusted self-growth and physiobiochemical
characteristics, and the intercross compatibility of T. chinensis to salt and
drought stresses can enhance the salt resistance under appropriate drought
stress, but the dominant factors influencing the physiological biochemical
characteristics of T. chinensis were various with the changing of salt-drought
intercross stresses gradients.
PMID- 25140349
TI - Distribution, microfabric, and geochemical characteristics of siliceous rocks in
central orogenic belt, China: implications for a hydrothermal sedimentation
model.
AB - Marine siliceous rocks are widely distributed in the central orogenic belt (COB)
of China and have a close connection to the geological evolution and
metallogenesis. They display periodic distributions from Mesoproterozoic to
Jurassic with positive peaks in the Mesoproterozoic, Cambrian--Ordovician, and
Carboniferous--Permian and their deposition is enhanced by the tensional
geological settings. The compressional regimes during the Jinning, Caledonian,
Hercynian, Indosinian, and Yanshanian orogenies resulted in sudden descent in
their distribution. The siliceous rocks of the Bafangshan-Erlihe ore deposit
include authigenic quartz, syn-depositional metal sulphides, and scattered
carbonate minerals. Their SiO2 content (71.08-95.30%), Ba (42.45-503.0 ppm), and
SigmaREE (3.28-19.75 ppm) suggest a hydrothermal sedimentation origin. As
evidenced by the Al/(Al + Fe + Mn), Sc/Th, (La/Yb) N, and (La/Ce) N ratios and
deltaCe values, the studied siliceous rocks were deposited in a marginal sea
basin of a limited ocean. We suggest that the Bafangshan-Erlihe area experienced
high- and low-temperature stages of hydrothermal activities. The hydrothermal
sediments of the former stage include metal sulphides and silica, while the
latter was mainly composed of silica. Despite the hydrothermal sedimentation of
the siliceous rocks, minor terrigenous input, magmatism, and biological activity
partly contributed to geochemical features deviating from the typical
hydrothermal characteristics.
PMID- 25140350
TI - Reinforcement learning for routing in cognitive radio ad hoc networks.
AB - Cognitive radio (CR) enables unlicensed users (or secondary users, SUs) to sense
for and exploit underutilized licensed spectrum owned by the licensed users (or
primary users, PUs). Reinforcement learning (RL) is an artificial intelligence
approach that enables a node to observe, learn, and make appropriate decisions on
action selection in order to maximize network performance. Routing enables a
source node to search for a least-cost route to its destination node. While there
have been increasing efforts to enhance the traditional RL approach for routing
in wireless networks, this research area remains largely unexplored in the domain
of routing in CR networks. This paper applies RL in routing and investigates the
effects of various features of RL (i.e., reward function, exploitation, and
exploration, as well as learning rate) through simulation. New approaches and
recommendations are proposed to enhance the features in order to improve the
network performance brought about by RL to routing. Simulation results show that
the RL parameters of the reward function, exploitation, and exploration, as well
as learning rate, must be well regulated, and the new approaches proposed in this
paper improves SUs' network performance without significantly jeopardizing PUs'
network performance, specifically SUs' interference to PUs.
PMID- 25140351
TI - Counteracting the inhibitory effect of proteins towards lung surfactant
substitutes: a fluorocarbon gas helps displace albumin at the air/water
interface.
AB - Perfluorohexane gas lowers the kinetic barrier that opposes the displacement of
albumin by dipalmitoylphosphatidylcholine at the air/water interface submitted to
sinusoidal oscillations at frequencies in the range of those encountered in
respiration.
PMID- 25140352
TI - Colorimetric and fluorescent determination of sulfide and sulfite with kinetic
discrimination.
AB - Two fluorescent probes, m-PSP and p-PSP , for sulfite and/or sulfide were
constructed by connecting a pyridinium ion to a coumarin fluorophore through an
alpha,beta-unsaturated ketone. The presence of the pyridinium salt promoted the
nucleophilic addition of sulfite and sulfide to the alpha,beta-unsaturated
ketone, which could be visualized by dramatic changes in the solution's color and
fluorescence intensity. Both probes exhibit good selectivity (the selectivity
coefficients toward major interferences are less than 0.07) and high sensitivity
for sulfite and sulfide over biothiols and other potential analytes. The
detection limits of m-PSP for the analysis of sulfite and sulfide are calculated
to 8.5 * 10(-7) M and 2.7 * 10(-7) M, respectively. Living cell imaging results
indicate that both probes can be applied in biological systems.
PMID- 25140353
TI - High-yield photolytic generation of brominated single-walled carbon nanotubes and
their application for gas sensing.
AB - We present a facile and efficient photobromination technique for the covalent
sidewall functionalization of SWNT using N-bromosuccinamide as the bromine
source. The modified bromine functionalized SWNTs are used as active agents in a
resistance measuring electrode system for sensing and discrimination of analyte
vapors.
PMID- 25140354
TI - GdF3 as a promising phosphopeptide affinity probe and dephospho-labelling medium:
experiments and theoretical explanation.
AB - Bone-like GdF3 was synthesized and applied for phosphopeptide enrichment for the
first time. As a new kind of efficient phosphopeptide affinity probe, GdF3
exhibits high efficiency in the mediation of the dephosphorylation reaction. In
addition, DFT calculations were introduced to theoretically explain the unique
property of GdF3 compared to GdPO4, which is promising and can be potentially
significant in protein phosphorylation research.
PMID- 25140355
TI - Lanthanoid beta-triketonates: a new class of highly efficient NIR emitters for
bright NIR-OLEDs.
AB - The reaction of hydrated YbCl3 with potassium tribenzoylmethanide yields a new
bimetallic tetranuclear Yb(3+)/K(+) assembly. This species not only possesses the
longest excited state lifetime and quantum yield reported for the Yb(3+)
diketonate family but is also suitable to be incorporated in NIR-OLEDs, whose
performance outclasses any other reported lanthanoid-based device with NIR
emission.
PMID- 25140356
TI - Reformation of organic dicarboxylate electrode materials for rechargeable
batteries by molecular self-assembly.
AB - We have found that the specific capacity of a Li-intercalated metal-organic
framework (iMOF) electrode material, 2,6-naphthalene dicarboxylate dilithium, can
be increased by narrowing the distance between naphthalene layers via ordering.
The increase in specific capacity can be attributed to formation of more
efficient electron and ion pathways in the framework.
PMID- 25140357
TI - Morphological effect of gold nanoparticles on the adsorption of bovine serum
albumin.
AB - Various properties of gold nanoparticles (GNPs) are found to play crucial roles
in their biological activity. Among them, the morphology and surface chemistry
are extremely important. This is because of differences in surface energies of
various crystal facets arising from a large fraction of edges, corners and
vertices. In the present work, we provide a comparative study on the adsorption
and binding affinities of bovine serum albumin (BSA) onto triangular gold
nanoplates (TGNP) and gold nanorods (GNR). The results were compared with similar
size of both CTAB and citrate stabilized spherical GNPs. Our data suggested
stronger binding of BSA on citrate stabilized spherical GNPs whereas TGNP shows
the weakest binding among all the GNPs. A blue shift of approximately 20 nm in
tryptophan fluorescence was observed for all CTAB stabilized GNPs, indicating the
local dielectric changes surrounding the tryptophan residue. Loss of the
secondary structure was also observed for all CTAB stabilized GNPs. No spectral
shift was observed for citrate stabilized spherical GNPs though maximum quenching
of fluorescence and minimum structural loss was observed. With the help of
molecular simulation recently developed by our group, a binding model is proposed
to explain all the above experimental results.
PMID- 25140358
TI - Anomalous high adsorption energy of H2O on fluorinated graphenes: a first
principles study.
AB - Polytetrafluoroethylene (PTFE) has been well-known for the surface
superhydrophobicity, while its two-dimensional stable analogues, CF and C4F,
possess distinct surface wettability. The CF inherits the hydrophobicity from
PTFE since the van der Waals interaction is mitigated by the high
electronegativity of fluorine. Surprisingly, a high adsorption energy (~550 meV
per molecule) of water has been unveiled on C4F via density functional theory
studies, implying anomalous superhydrophilicity of C4F. The abrupt transition
from hydrophobicity of CF to superhydrophilicity of C4F can be reconciled with
the difference in their molecular orbitals. The high adsorption energy of C4F is
mainly attributed to the Coulomb attraction among the non-bonding interactions,
as proposed by our theoretical model. Since the surface chemical inertness of CF
inhibits it from being widely adopted in device fabrication, the present finding
suggests that C4F can be a promising candidate in graphene-based electronic
devices.
PMID- 25140359
TI - Tip-enhanced Raman spectroscopic measurement of stress change in the local domain
of epitaxial graphene on the carbon face of 4H-SiC(000-1).
AB - We develop a bulk silver tip for tip-enhanced Raman scattering (TERS) and obtain
TERS spectra of epitaxial graphene on the carbon face of 4H-SiC(000-1) with a
high signal-to-noise ratio. Thanks to the high quality of TERS spectra we firstly
find that the G band in the TERS spectra exhibits position-by-position variations
in both lower wavenumber shifts and spectral broadening. The analysis of the
variations reveals that the shifts and broadenings have a linear correlation
between each other, indicating that the variations are induced by the position
dependent local stress on graphene based on a uniaxial strain model.
PMID- 25140360
TI - Electronic stability and electron transport properties of atomic wires anchored
on the MoS2 monolayer.
AB - The stability, electronic structure, and electron transport properties of
metallic monoatomic wires anchored on the MoS2 monolayer are investigated within
the density functional theory. The anchoring of the atomic wires on the
semiconducting monolayer significantly modifies its electronic properties; the
metallic characteristics of the assembled monolayers appear in the density of
states and band structure of the system. We find that Cu, Ag and Au wires induce
the so-called n-type doping effect, whereas Pt wires induce a p-type doping
effect in the monolayer. The distinctly different behavior of Pt-MoS2 compared to
the rest of the metallic wires is reflected in the calculated current-voltage
characteristics of the assembled monolayers with a highly asymmetric behavior of
the out-of-the-plane tunneling current with respect to the polarity of the
external bias. The results of the present study are likely to extend the
functionality of the MoS2 monolayer as a candidate material for the novel
applications in the areas of catalysis and optoelectronic devices.
PMID- 25140361
TI - Agarose gel investigation of quantum dots conjugated with short ssDNA.
AB - Herein, we investigate the migration distance of quantum-dot-functionalized
complexes in electrophoresis. The quantitative study of these moving particles in
an electrophoretic environment is modeled using an extended Smoluchowski
equation. An extended Smoluchowski equation is proposed to addressed the D(m) to
Ln(N) plot slope variation issue present in previous work and agreement between
experiment and theory is found. The procedures underlying this work then
discusses the potential of using agarose electrophoresis as a mean of monitoring
the composition of nano-complexes consisting of quantum dots functionalized with
differing numbers of DNA molecules.
PMID- 25140362
TI - Cluster algebras.
PMID- 25140363
TI - Reducing complications from obstructive sleep apnoea.
PMID- 25140366
TI - Japan: in the wake of the 2011 tsunami.
PMID- 25140365
TI - Third-generation EGFR-TKIs-a new hope for NSCLC.
PMID- 25140364
TI - 2014 American Thoracic Society International Conference.
PMID- 25140367
TI - AstraZeneca Pharmaceuticals launches in Zambia.
PMID- 25140369
TI - Sports cardiology: preventing sudden cardiac death.
PMID- 25140370
TI - Visual working memory. Models of response times.
PMID- 25140371
TI - Spatiotemporal context. How past perception influences current perception.
PMID- 25140372
TI - Attention and reward. The power of reward to rewire attention.
PMID- 25140373
TI - Color vision. The "geopolitics" of basic color terms.
PMID- 25140374
TI - Timing. Autocracy versus democracy in a string quartet.
PMID- 25140375
TI - Artistic skill and object perception. Drawing skill: neither the eye nor the
hand, but something in between.
PMID- 25140376
TI - Authors' reply.
PMID- 25140377
TI - Reply to the 'Comment on comparison of powder dustiness methods' by Douglas
Evans, Leonid Turkevich, Cynthia Roettgers, and Gregory Deye (Ann. Occup. Hyg.,
2014, Vol. 58, No. 4, 524-8).
PMID- 25140378
TI - Reply to the letters to the editor submitted by T. L. Ogden and K.T. Du Clos, and
by R. Foster regarding the paper 'SWeRF-a method for estimating the relevant fine
particle fraction in bulk materials for classification and labelling purposes'.
AB - The authors respond to the points raised in the Letters to the Editor raised by
Ogden and Du Clos and by Foster. Ad 1: The debate of the classification of
respirable cyrstalline silica is outside the scope of the technical paper. Ad 2:
A standard for the determination of SWeRF is under development, in which indeed
the provision is made that for a correct determination all quartz within the fine
fraction needs to be liberated. Ad 3: Dustiness tests provide useful information
for occupational hygienists, but are not suitable for fulfilling classification
and labelling requirements. Ad 4: Pipette effects are not discussed in the paper
because the difference between calculating the SWeRF from the particle size
distribution and the SWeRF from sedimentation is very small.
PMID- 25140380
TI - Supermarket smarts. Diner-style breakfast foods.
PMID- 25140379
TI - Aging and DNA damage in humans: a meta-analysis study.
AB - Age-related DNA damage is regarded as one of the possible explanations of aging.
Although a generalized idea about the accumulation of DNA damage with age exists,
results found in the literature are inconsistent. To better understand the
question of age-related DNA damage in humans and to identify possible moderator
variables, a metaanalysis was conducted. Electronic databases and bibliographies
for studies published since 2004 were searched. Summary odds ratios (ORs) and 95%
confidence intervals (CIs) for age-related DNA damage were calculated in a random
effects model. A total of 76 correlations from 36 studies with 4676 participants
were included. Based on our analysis, a correlation between age and DNA damage
was found (r=0.230, p=0.000; 95% confidence interval=0.111-0.342). The test for
heterogeneity of variance indicates that the study's results are significantly
high (Q (75)=1754.831, p=0.000). Moderator variables such as smoking habits,
technique used, and the tissue/sample analyzed, are shown to influence age
related DNA damage (p=0.026; p=0.000; p=0.000, respectively). Nevertheless, sex
did not show any influence on this relation (p=0.114). In conclusion, this meta
analysis showed an association between age and DNA damage in humans. It was also
found that smoking habits, the technique used, and tissue/sample analyzed, are
important moderator variables in age-related DNA damage.
PMID- 25140381
TI - Most profitable U.S. health insurance companies. Ranked by 2013 profit margin.
PMID- 25140382
TI - Largest not-for-profit hospital systems. Ranked by total revenue for 2013.
PMID- 25140383
TI - Conductance control in VO2 nanowires by surface doping with gold nanoparticles.
AB - The material properties of semiconductor nanowires are greatly affected by
electrical, optical, and chemical processes occurring at their surfaces because
of the very large surface-to-volume ratio. Precise control over doping as well as
the surface charge properties has been demonstrated in thin films and nanowires
for fundamental physics and application-oriented research. However, surface
doping behavior is expected to differ markedly from bulk doping in conventional
semiconductor materials. Here, we show that placing gold nanoparticles, in
controlled manner, on the surface of an insulating vanadium dioxide nanowire
introduces local charge carriers in the nanowire, and one could, in principle,
completely and continuously alter the material properties of the nanowire and
obtain any intermediate level of conductivity. The current in the nanowire
increased by nearly 3 times when gold nanoparticles of 10(11) cm(-2) order of
density were controllably placed on the nanowire surface. A strong quadratic
space-charge limited (SCL) transport behavior was also observed from the
conductance curve suggesting the formation of two-dimensional (2D) electron-gas
like confined layer in the nanowire with adsorbed Au NPs. In addition to
stimulating scientific interest, such unusual surface doping phenomena may lead
to new applications of vanadium dioxide-based electronic, optical, and chemical
sensing nanodevices.
PMID- 25140384
TI - Weakly anti-inflammatory limonoids from the seeds of Xylocarpus rumphii.
AB - Seven new limonoids, namely, xylorumphiins E-J (1-2 and 4-7) and 2
hydroxyxylorumphiin F (3), along with three known derivatives (8-10), were
isolated from the seeds of Xylocarpus rumphii. 2-Hydroxyxylorumphiin F (3) and
xylorumphiin I (6) displayed moderate inhibitory activity against nitric oxide
production from lipopolysaccharide-activated macrophages with IC50 values of 24.5
and 31.3 MUM, respectively.
PMID- 25140385
TI - 13C NMR metabolomics: applications at natural abundance.
AB - (13)C NMR has many advantages for a metabolomics study, including a large
spectral dispersion, narrow singlets at natural abundance, and a direct measure
of the backbone structures of metabolites. However, it has not had widespread use
because of its relatively low sensitivity compounded by low natural abundance.
Here we demonstrate the utility of high-quality (13)C NMR spectra obtained using
a custom (13)C-optimized probe on metabolomic mixtures. A workflow was developed
to use statistical correlations between replicate 1D (13)C and (1)H spectra,
leading to composite spin systems that can be used to search publicly available
databases for compound identification. This was developed using synthetic
mixtures and then applied to two biological samples, Drosophila melanogaster
extracts and mouse serum. Using the synthetic mixtures we were able to obtain
useful (13)C-(13)C statistical correlations from metabolites with as little as 60
nmol of material. The lower limit of (13)C NMR detection under our experimental
conditions is approximately 40 nmol, slightly lower than the requirement for
statistical analysis. The (13)C and (1)H data together led to 15 matches in the
database compared to just 7 using (1)H alone, and the (13)C correlated peak lists
had far fewer false positives than the (1)H generated lists. In addition, the
(13)C 1D data provided improved metabolite identification and separation of
biologically distinct groups using multivariate statistical analysis in the D.
melanogaster extracts and mouse serum.
PMID- 25140387
TI - Mixtures as a fungicide resistance management tactic.
AB - We have reviewed the experimental and modeling evidence on the use of mixtures of
fungicides of differing modes of action as a resistance management tactic. The
evidence supports the following conclusions. 1. Adding a mixing partner to a
fungicide that is at-risk of resistance (without lowering the dose of the at-risk
fungicide) reduces the rate of selection for fungicide resistance. This holds for
the use of mixing partner fungicides that have either multi-site or single-site
modes of action. The resulting predicted increase in the effective life of the at
risk fungicide can be large enough to be of practical relevance. The more
effective the mixing partner (due to inherent activity and/or dose), the larger
the reduction in selection and the larger the increase in effective life of the
at-risk fungicide. 2. Adding a mixing partner while lowering the dose of the at
risk fungicide reduces the selection for fungicide resistance, without
compromising effective disease control. The very few studies existing suggest
that the reduction in selection is more sensitive to lowering the dose of the at
risk fungicide than to increasing the dose of the mixing partner. 3. Although
there are very few studies, the existing evidence suggests that mixing two at
risk fungicides is also a useful resistance management tactic. The aspects that
have received too little attention to draw generic conclusions about the
effectiveness of fungicide mixtures as resistance management strategies are as
follows: (i) the relative effect of the dose of the two mixing partners on
selection for fungicide resistance, (ii) the effect of mixing on the effective
life of a fungicide (the time from introduction of the fungicide mode of action
to the time point where the fungicide can no longer maintain effective disease
control), (iii) polygenically determined resistance, (iv) mixtures of two at-risk
fungicides, (v) the emergence phase of resistance evolution and the effects of
mixtures during this phase, and (vi) monocyclic diseases and nonfoliar diseases.
The lack of studies on these aspects of mixture use of fungicides should be a
warning against overinterpreting the findings in this review.
PMID- 25140386
TI - Targeting of plasminogen activator inhibitor 1 improves fibrinolytic therapy for
tetracycline-induced pleural injury in rabbits.
AB - Endogenous active plasminogen activator inhibitor 1 (PAI-1) was targeted in vivo
with monoclonal antibodies (mAbs) that redirect its reaction with proteinases to
the substrate branch. mAbs were used as an adjunct to prourokinase (single-chain
[sc] urokinase [uPA]) intrapleural fibrinolytic therapy (IPFT) of tetracycline
induced pleural injury in rabbits. Outcomes of scuPA IPFT (0.25 or 0.0625 mg/kg)
with 0.5 mg/kg of mouse IgG or mAbs (MA-33H1F7 and MA-8H9D4) were assessed at 24
hours. Pleural fluid (PF) was collected at 0, 10, 20, and 40 minutes and 24 hours
after IPFT and analyzed for plasminogen activating (PA), uPA, fibrinolytic
activities, levels of total plasmin/plasminogen, alpha-macroglobulin (alphaM),
mAbs/IgG antigens, free active uPA, and alphaM/uPA complexes. Anti-PAI-1 mAbs,
but not mouse IgG, delivered with an eightfold reduction in the minimal effective
dose of scuPA (from 0.5 to 0.0625 mg/kg), improved the outcome of IPFT (P <
0.05). mAbs and IgG were detectable in PFs at 24 hours. Compared with identical
doses of scuPA alone or with IgG, treatment with scuPA and anti-PAI-1 mAbs
generated higher PF uPA amidolytic and PA activities, faster formation of
alphaM/uPA complexes, and slower uPA inactivation. However, PAI-1 targeting did
not significantly affect intrapleural fibrinolytic activity or levels of total
plasmin/plasminogen and alphaM antigens. Targeting PAI-1 did not induce bleeding,
and rendered otherwise ineffective doses of scuPA able to improve outcomes in
tetracycline-induced pleural injury. PAI-1-neutralizing mAbs improved IPFT by
increasing the durability of intrapleural PA activity. These results suggest a
novel, well-tolerated IPFT strategy that is tractable for clinical development.
PMID- 25140388
TI - Potential effects of diurnal temperature oscillations on potato late blight with
special reference to climate change.
AB - Global climate change will have effects on diurnal temperature oscillations as
well as on average temperatures. Studies on potato late blight (Phytophthora
infestans) development have not considered daily temperature oscillations. We
hypothesize that growth and development rates of P. infestans would be less
influenced by change in average temperature as the magnitude of fluctuations in
daily temperatures increases. We investigated the effects of seven constant (10,
12, 15, 17, 20, 23, and 27 degrees C) and diurnally oscillating (+/-5 and +/-10
degrees C) temperatures around the same means on number of lesions, incubation
period, latent period, radial lesion growth rate, and sporulation intensity on
detached potato leaves inoculated with two P. infestans isolates from clonal
lineages US-8 and US-23. A four-parameter thermodynamic model was used to
describe relationships between temperature and disease development measurements.
Incubation and latency progression accelerated with increasing oscillations at
low mean temperatures but slowed down with increasing oscillations at high mean
temperatures (P < 0.005), as hypothesized. Infection efficiency, lesion growth
rate, and sporulation increased under small temperature oscillations compared
with constant temperatures but decreased when temperature oscillations were
large. Thus, diurnal amplitude in temperature should be considered in models of
potato late blight, particularly when predicting effects of global climate change
on disease development.
PMID- 25140389
TI - Nanoscopic poly-DNA-cleaver for breast cancer regression with induced oxidative
damage.
AB - A novel strategy for efficient "nanodelivery" of DNA-cleaving molecules for
breast cancer regression is presented here. The synthetic methodology can be
tweaked for controlled delivery and better bioavailability of effective doses of
these DNA-cleaving agents through a defined self-assembled polymeric
nanoarchitecture. In vitro studies in ER+ and ER- breast cancer human cell lines
confirmed an efficient "nano"-delivery of DNA-cleaving molecules and indicated
their capability to mediate oxidative damage to nucleobases and/or to the 2
deoxyribose moiety. Prepared E-poly-DNA-cleaver and C-poly-DNA-cleaver were found
to be interacting with plasmid DNA pBR322 (pDNA) and active to cause oxidative
cleavage of pDNA in the presence of ascorbic acid and H2O2. They were found to be
significantly active as DNA cleaving agents in vitro and showed highly improved
cancer regression in MCF-7 and MD-MB231 cancer cells compared to small molecule
DNA cleaver. Surface conjugated nanoparticles were found to be more effective
than noncovalent encapsulation and the small molecule agent, whereas in all the
cases RCM was significantly inactive toward DNA cleavage. Blood contact
complement activation properties were evaluated to gauge their likelihood to
promote acute toxicity following systemic administration. The complement
activation analyses together with the blood smear study confirm the feasibility
of using these poly-DNA-cleavers without risk of induced immune response.
PMID- 25140390
TI - Irradiation with X-rays phase-advances the molecular clockwork in liver, adrenal
gland and pancreas.
AB - The circadian clock of man and mammals shows a hierarchic organization. The
master clock, located in the suprachiasmatic nuclei (SCN), controls peripheral
oscillators distributed throughout the body. Rhythm generation depends on
molecular clockworks based on transcriptional/translational interaction of clock
genes. Numerous studies have shown that the clockwork in peripheral oscillators
is capable to maintain circadian rhythms for several cycles in vitro, i.e. in the
absence of signals from the SCN. The aim of the present study is to analyze the
effects of irradiation with X-rays on the clockwork of liver, adrenal and
pancreas. To this end organotypic slice cultures of liver (OLSC) and organotypic
explant cultures of adrenal glands (OAEC) and pancreas (OPEC) were prepared from
transgenic mPer2(luc) mice which express luciferase under the control of the
promoter of an important clock gene, Per2, and allow to study the dynamics of the
molecular clockwork by bioluminometry. The preparations were cultured in a
membrane-based liquid-air interface culturing system and irradiated with X-rays
at doses of 10 Gy and 50 Gy or left untreated. Bioluminometric real-time
recordings show a stable oscillation of all OLSC, OAEC and OPEC for up to 12 days
in vitro. Oscillations persist after irradiation with X-rays. However, a dose of
50 Gy caused a phase advance in the rhythm of the OLSC by 5 h, in the OPEC by 7 h
and in the OAEC by 6 h. Our study shows that X-rays affect the molecular
clockwork in liver, pancreas and adrenal leading to phase advances. Our results
confirm and extend previous studies showing a phase-advancing effect of X-rays at
the level of the whole animal and single cells.
PMID- 25140391
TI - The mouse liver displays daily rhythms in the metabolism of phospholipids and in
the activity of lipid synthesizing enzymes.
AB - The circadian system involves central and peripheral oscillators regulating
temporally biochemical processes including lipid metabolism; their disruption
leads to severe metabolic diseases (obesity, diabetes, etc). Here, we
investigated the temporal regulation of glycerophospholipid (GPL) synthesis in
mouse liver, a well-known peripheral oscillator. Mice were synchronized to a
12:12 h light-dark (LD) cycle and then released to constant darkness with food ad
libitum. Livers collected at different times exhibited a daily rhythmicity in
some individual GPL content with highest levels during the subjective day. The
activity of GPL-synthesizing/remodeling enzymes: phosphatidate phosphohydrolase 1
(PAP-1/lipin) and lysophospholipid acyltransferases (LPLATs) also displayed
significant variations, with higher levels during the subjective day and at dusk.
We evaluated the temporal regulation of expression and activity of
phosphatidylcholine (PC) synthesizing enzymes. PC is mainly synthesized through
the Kennedy pathway with Choline Kinase (ChoK) as a key regulatory enzyme or
through the phosphatidylethanolamine (PE) N-methyltransferase (PEMT) pathway. The
PC/PE content ratio exhibited a daily variation with lowest levels at night,
while ChoKalpha and PEMT mRNA expression displayed maximal levels at nocturnal
phases. Our results demonstrate that mouse liver GPL metabolism oscillates
rhythmically with a precise temporal control in the expression and/or activity of
specific enzymes.
PMID- 25140392
TI - Levels of neopterin and C-reactive protein in pregnant women with fetal growth
restriction.
AB - The aim of this study was to evaluate whether pregnant women with fetal growth
restriction (FGR) have higher plasma neopterin and C-reactive protein (CRP)
concentrations compared with those with uncomplicated pregnancy. A total of 34
pregnant women with FGR and 62 patients with uncomplicated pregnancy were
included. Neopterin and CRP levels were measured at the time of diagnosis. The
primary outcome of this study was to compare the neopterin and CRP levels in
pregnant women with FGR and those with uncomplicated pregnancies. The secondary
outcome of our study was to evaluate the correlation between fetal birth weight
and maternal neopterin levels. The serum neopterin levels were significantly
elevated in pregnant women with FGR (22.71 +/- 7.70 vs 19.15 +/- 8.32). However,
CRP was not elevated in pregnant women with FGR (7.47 +/- 7.59 vs 5.29 +/- 3.58).
These findings support the hypothesis that pregnancy with FGR is associated with
a marked increase in macrophage activation and the natural immune system.
PMID- 25140394
TI - SOX3 deletion in mouse and human is associated with persistence of the
craniopharyngeal canal.
AB - CONTEXT: SOX3 is an early developmental transcription factor involved in
pituitary development. In humans, over- and underdosage of SOX3 is associated
with X-linked hypopituitarism with variable phenotypes ranging from isolated GH
deficiency (GHD) to panhypopituitarism, with or without mental retardation and,
in most cases, with reported pituitary imaging, an ectopic/undescended posterior
pituitary. PATIENT: We present a young patient with hemophilia B and
developmental delay who had a 2.31-Mb deletion on Xq27 including SOX3, F9, and
eight other contiguous genes. He developed GH and gonadotropin deficiency, whilst
his thyroid function was in the low normal range. Magnetic resonance imaging
revealed a eutopic posterior pituitary and the unusual finding of a persistent
craniopharyngeal canal that has not previously been described in patients with
congenital hypopituitarism. OBJECTIVE AND METHODS: To establish whether loss of
SOX3 can account for the human phenotype, we examined in detail the hypothalamo
pituitary region of neonatal Sox3 null mice. RESULTS: Consistent with the
patient's phenotype, Sox3 null mice exhibit a ventral extension of the anterior
pituitary that penetrates, and generates a mass beneath, the sphenoid bone. This
suggests that the defect results from abnormal induction of Rathke's pouch,
leading to a persistent connection between Rathke's pouch and the oral ectoderm.
CONCLUSIONS: Our observations expand the spectrum of phenotypes observed in
association with altered SOX3 dosage and may affect the approach to genetic
screening. Screening for SOX3 should be advised not only for hypopituitary
patients with an ectopic posterior pituitary, but also for those with a
structurally normal pituitary and additional findings, including clefts and a
persistent craniopharyngeal canal, with or without mental retardation.
PMID- 25140395
TI - Factors associated with bone mineral density and risk of fall in Korean adults
with type 2 diabetes mellitus aged 50 years and older.
AB - CONTEXT: Osteoporotic fractures in subjects with diabetes mellitus (DM) carry
higher mortality and morbidity. Because bone strength and minor trauma, such as a
falls, are considered to be significant factors contributing to osteoporotic
fractures, it is important to elucidate the associated factors with these.
OBJECTIVE: This study was performed to investigate the factors associated with
bone mineral density (BMD) and falls in noninstitutionalized subjects with DM
aged 50 years or older. DESIGN, SETTING, AND PATIENTS: We used the database from
the 2010 Fifth Korea National Health and Nutrition Examination Survey. Subjects
with DM aged 50 years or older were selected and included in the data analyses.
Associated factors with BMD of the femoral neck and lumbar spine and those with
falls were analyzed using multiple linear regression and binary logistic
regression analyses, respectively. RESULTS: Three hundred sixty-two subjects [209
males; 153 females; average age, 66.0 y (SD 8.2 y)] were included. Among the male
subjects, the total body muscle mass (P < .001), daily calcium intake (P = .001),
ALP levels (P = .007), and body mass index (P = .027) were significantly
associated with femoral neck BMD, whereas body mass index (P = .001) and ALP
levels (P = .040) were associated with lumbar spine BMD. Among the female
subjects, age (P < .001), daily calcium intake (P = .011) and total body muscle
mass (P = .023) were found to be significantly associated factors with femoral
neck BMD, whereas age (P < .001) and body mass index (P = .012) and daily calcium
intake (P = .040) were those with lumbar spine BMD. Osteoarthritis (P = .024) and
total body muscle mass (P = .028) were found to be significantly associated with
the risk of falls. CONCLUSIONS: Total body muscle mass was the most prominent
factor predicting femoral neck BMD and risk of falls in community-dwelling
elderly subjects with DM. Further investigation is required to determine their
role in preventing osteoporotic fractures in diabetic subjects.
PMID- 25140396
TI - Dose-dependent effects of rosuvastatin on the plasma sphingolipidome and
phospholipidome in the metabolic syndrome.
AB - CONTEXT: Statins are effective cholesterol-lowering agents that reduce
cardiovascular disease risk but also have pleiotropic effects that may extend to
other lipid classes. OBJECTIVE: The purpose of this article was to investigate,
in a post hoc analysis, the dose-dependent effects of rosuvastatin on plasma
sphingolipids and phospholipids in men with the metabolic syndrome. METHODS:
Subjects (n = 12) were studied in a randomized, double-blind, triple-crossover
trial of a 5-week treatment period with placebo or rosuvastatin (10 or 40 mg/day)
with 2-week washouts between treatments. Plasma sphingolipid profiling was
determined by liquid chromatography electrospray ionization-tandem mass
spectrometry. RESULTS: Rosuvastatin at 10 mg/d (R10) and 40 mg/d (R40)
significantly (all P < .001 unless stated otherwise) lowered plasma cholesterol (
34% and -42% [% change with R10 and with R40, respectively]), low-density
lipoprotein cholesterol (-49% and -57%) and triglyceride (-24%, P =.03 and -42%)
concentrations. Compared with placebo, R10 and R40 significantly decreased the
plasma levels of total sphingolipids including those of ceramide (-33% and -37%),
sphingomyelin (-27% and -31%), monohexosylceramide (-40% and -47%),
dihexosylceramide (-31% and -34%), and trihexosylceramide (-29% and -31%), and
GM3 gangliosides (-29% and -26%), lysophosphatidylcholine (-32% and -37%),
alkylphosphatidylcholine (-19% and -19%), phosphatidylcholine (-17% and -19%),
alkenylphosphatidylcholine (plasmalogen) (-20% and -22%),
alkylphosphatidylethanolamine (-20%, P =.008 and -24%, P =.02),
alkenylphosphatidylethanolamine (plasmalogen) (-24%, P =.003 and -23%, P =.007),
phosphatidylglycerol (-24%, P =.07, -31%, P =.046), and phosphatidylinositol (
34% and -40%). No significant changes were found with phosphatidylethanolamine
and phosphatidylserine. Significant dose effects were found with the majority of
the plasma sphingolipids, whereas only phosphatidylcholine,
lysophosphatidylcholine, alkylphosphatidylcholine, alkenylphosphatidylcholine
(plasmalogen), and phosphatidylinositol had significant dose effects. Similar
changes were found with plasma sphingolipids when results were normalized to the
total phosphatidylcholine concentration. CONCLUSIONS: Rosuvastatin dose
dependently lowers plasma sphingolipids and phospholipids, independent of low
density lipoprotein lowering, in men with the metabolic syndrome.
PMID- 25140393
TI - mRNA-binding protein TIA-1 reduces cytokine expression in human endometrial
stromal cells and is down-regulated in ectopic endometrium.
AB - BACKGROUND: Cytokines and growth factors play important roles in endometrial
function and the pathogenesis of endometriosis. mRNAs encoding cytokines and
growth factors undergo rapid turnover; primarily mediated by adenosine- and
uridine-rich elements (AREs) located in their 3'-untranslated regions. T-cell
intracellular antigen (TIA-1), an mRNA-binding protein, binds to AREs in target
transcripts, leading to decreased gene expression. OBJECTIVE: The purpose of this
article was to determine whether TIA-1 plays a role in the regulation of
endometrial cytokine and growth factor expression during the normal menstrual
cycle and whether TIA-1 expression is altered in women with endometriosis.
METHODS: Eutopic endometrial tissue obtained from women without endometriosis (n
= 30) and eutopic and ectopic endometrial tissues from women with endometriosis
(n = 17) were immunostained for TIA-1. Staining intensities were evaluated by
histological scores (HSCOREs). The regulation of endometrial TIA-1 expression by
immune factors and steroid hormones was studied by treating primary cultured
human endometrial stromal cells (HESCs) with vehicle, lipopolysaccharide, TNF
alpha, IL-6, estradiol, or progesterone, followed by protein blot analyses. HESCs
were engineered to over- or underexpress TIA-1 to test whether TIA-1 regulates IL
6 or TNF-alpha expression in these cells. RESULTS: We found that TIA-1 is
expressed in endometrial stromal and glandular cells throughout the menstrual
cycle and that this expression is significantly higher in the perimenstrual
phase. In women with endometriosis, TIA-1 expression in eutopic and ectopic
endometrium was reduced compared with TIA-1 expression in eutopic endometrium of
unaffected control women. Lipopolysaccharide and TNF-alpha increased TIA-1
expression in HESCs in vitro, whereas IL-6 or steroid hormones had no effect. In
HESCs, down-regulation of TIA-1 resulted in elevated IL-6 and TNF-alpha
expression, whereas TIA-1 overexpression resulted in decreased IL-6 and TNF-alpha
expression. CONCLUSIONS: Endometrial TIA-1 is regulated throughout the menstrual
cycle, TIA-1 modulates the expression of immune factors in endometrial cells, and
downregulation of TIA-1 may contribute to the pathogenesis of endometriosis.
PMID- 25140397
TI - Plasma parathyroid hormone is associated with vascular dementia and cerebral
hyperintensities in two community-based cohorts.
AB - CONTEXT: In diseases with increased PTH such as hyperparathyroidism and chronic
renal failure, dementia is common. Little is known of PTH and dementia in the
community. OBJECTIVE: We sought to investigate relations between PTH, clinical
dementia and cerebral micro-vascular disease. SETTING AND DESIGN: The Uppsala
Longitudinal Study Of Adult Men (ULSAM) was prospective, baseline, 1991-1995;
followup, 15.8 years. The Prospective Investigation Of The Vasculature In Uppsala
Seniors (PIVUS) was cross-sectional, baseline, 2001. Both settings were community
based. PARTICIPANTS AND MAIN OUTCOME MEASURE: In the ULSAM study of 998 men (age
71) the association between PTH and dementia was investigated. In the PIVUS study
of 406 men and women (age 70) the relation between PTH and magnetic resonance
imaging signs of cerebral small vascular disease was investigated. RESULTS:
During followup, 56 individuals were diagnosed with vascular, 91 with
Alzheimer's, and 59 with other dementias. In Cox-regression analyses, higher PTH
was associated with vascular dementia (hazard ratio per 1 SD increase of PTH,
1.41; P < .01), but not with other dementias. The top tertile of PTH accounted
for 18.5% of the population-attributable risk for vascular dementia, exceeding
all other risk factors. In linear regression analysis in PIVUS, PTH was
associated with increasing white matter hyperintensities (WMHI), reflecting
increasing burden of cerebral small vessel disease (1 SD PTH increase, 0.31
higher category of WMHI; P = .016). All models were adjusted for vascular risk
factors and mineral metabolism. CONCLUSIONS: In two community-based samples, PTH
predicted clinically diagnosed vascular dementia as well as neuroimaging indices
of cerebral small vessel disease. Our data suggest a role for PTH in the
development of vascular dementia.
PMID- 25140398
TI - Approach to the patient: transgender youth: endocrine considerations.
AB - Compelling studies have demonstrated that "gender identity"--a person's inner
sense of self as male, female, or occasionally a category other than male or
female--is not simply a psychosocial construct, but likely reflects a complex
interplay of biological, environmental, and cultural factors. An increasing
number of preadolescents and adolescents, identifying as "transgender" (a
transient or persistent identification with a gender different from their "natal
gender"--ie, the gender that is assumed based on the physical sex characteristics
present at birth), are seeking medical services to enable the development of
physical characteristics consistent with their affirmed gender. Such services,
including the use of agents to block endogenous puberty at Tanner stage 2 and
subsequent use of cross-sex hormones, are based on longitudinal studies
demonstrating that those individuals who were first identified as gender
dysphoric in early or middle childhood and who still meet the mental health
criteria for being transgender at early puberty are likely to be transgender as
adults. Furthermore, onset of puberty in transgender youth is often accompanied
by increased "gender dysphoria"--clinically significant distress related to the
incongruence between one's affirmed gender and one's "assigned (or natal)
gender." Studies have shown that such distress may be ameliorated by a "gender
affirming" model of care. Although endocrinologists are familiar with concerns
surrounding gender identity in patients with disorders of sex development, many
providers are unfamiliar with the approach to the evaluation and management of
transgender youth without a disorder of sex development. The goals of this
article are to review studies that shed light on the biological underpinnings of
gender identity, the epidemiology and natural history of transgenderism, current
clinical practice guidelines for transgender youth, and limitations and
challenges to optimal care. Prospective cohort studies focused on long-term
safety and efficacy are needed to optimize medical and mental health care for
transgender youth.
PMID- 25140399
TI - TGF-beta1 downregulates StAR expression and decreases progesterone production
through Smad3 and ERK1/2 signaling pathways in human granulosa cells.
AB - CONTEXT: Regulation of progesterone production in granulosa cells is important
for normal reproductive functions. Steroidogenic acute regulatory protein (StAR)
is recognized as the key regulatory protein involved in the rate-limiting step of
steroidogenesis. TGF-beta1 protein is detected in human follicular fluid, and TGF
beta1 and its receptors are expressed in human granulosa cells. However, the
functional role of TGF-beta1 in the regulation of StAR expression and
progesterone production in human granulosa cells remains unknown. OBJECTIVE: Our
objective was to investigate the effects of TGF-beta1 on StAR expression and
progesterone production in human granulosa cells. DESIGN AND SETTING: SVOG cells
are human granulosa cells that were obtained from women undergoing in vitro
fertilization and immortalized with SV40 large T antigen. SVOG cells were used to
investigate the effects of TGF-beta1 on StAR expression and progesterone
production at an academic research center. MAIN OUTCOME MEASURES: Levels of mRNA
and protein were examined by RT-qPCR and western blotting, respectively. The
accumulation levels of progesterone were measured by enzyme-linked immunosorbent
assay (ELISA). RESULTS: TGF-beta1 treatment downregulated StAR expression and
decreased progesterone production. The suppressive effects of TGF-beta1 on StAR
expression and progesterone production were abolished by the inhibition of TGF
beta type I receptor. In addition, treatment with TGF-beta1 activated the Smad2/3
and ERK1/2 signaling pathways. The inhibition of the Smad3 and ERK1/2 signaling
pathways attenuated the TGF-beta1-induced downregulation of StAR expression and
progesterone production. CONCLUSION: TGF-beta1 downregulated StAR expression and
decreased progesterone production by activating the Smad3 and ERK1/2 signaling
pathways in human granulosa cells.
PMID- 25140400
TI - Elimination of pain and improvement of exercise capacity in Camurati-Engelmann
disease with losartan.
AB - BACKGROUND: Camurati-Engelmann disease (CED) is a rare disorder, with
approximately 250 described cases in the literature. Treatment options are
limited and have been suboptimal so far. PATIENT AND METHODS: A prepubertal girl
aged 9 years was diagnosed with CED. Treatment with losartan was initiated at a
daily dose of 0.75 mg/kg. Over a period of 12 weeks, the dose was gradually
increased to 1.0 mg/kg/d. The patient was reviewed in clinic regularly and
underwent thorough clinical assessments 9, 17, and 38 months after treatment
initiation. RESULTS: The patient experienced marked clinical improvements with
losartan. In particular, losartan treatment led to the complete elimination of
the previously severe and incapacitating pain, with an increased ability to walk
and perform physical activities. There was also a considerable improvement in
body composition with increased lean and adipose tissue. Notably, the improvement
in fat deposition had not been previously observed with other treatments in CED.
Hematology, liver, and renal function tests were within normal ranges at
presentation and remained so over the course of treatment. CONCLUSIONS: In light
of our findings, losartan may be a useful option in CED management.
PMID- 25140402
TI - Less myostatin and more lean mass in large-born infants from nondiabetic mothers.
AB - CONTEXT AND OBJECTIVE: Sexagenarians born large are at lower risk for type 2
diabetes than those born small, a key feature of their body composition being a
higher muscle mass, which explains their higher body mass index and also their
lower fat-to-lean-mass ratio. Myogenesis is completed in early infancy under the
inhibitory control of myostatin. We tested whether large-born infants from
nondiabetic mothers develop an early surplus of lean mass while having a lower
myostatinemia. Design, Methods, Study Participants, and Main Outcomes: In a
longitudinal study (0-4 mo), we compared the body composition and endocrine
markers (fasting glucose, insulin, IGF-1, high molecular weight adiponectin) of
breast-fed appropriate- vs large-for-gestational-age infants (n = 125) from
nondiabetic mothers. Circulating myostatin concentrations were assayed after
collection of the above-mentioned data. SETTING: The study was conducted at the
University Hospital for Women and Children. INTERVENTION: There were no
interventions. RESULTS: Between 0-4 months, large-for-gestational-age infants
switched from an adipose to a lean body composition (due to a nearly 20% excess
of lean mass) and to an insulin-sensitive and hyperadiponectinemic state while
having low IGF-1 concentrations and the lowest myostatinemia hitherto reported in
the human (all between P <= .01 and P <= .0001). CONCLUSION: Large-born infants
from nondiabetic mothers were found to combine a low myostatinemia with an excess
of lean mass. The fetal-neonatal control of myostatinemia deserves further
attention because it could become a target of interventions that aim at reducing
the risk for diabetes in later life by augmenting myogenesis in early life.
PMID- 25140401
TI - Functional analysis of novel genetic variation in the thyroid hormone activating
type 2 deiodinase.
AB - CONTEXT: Thyroid hormones (TH) are important for normal brain development and
abnormal TH regulation in the brain results in neurocognitive impairments. The
type 2 deiodinase (D2) is important for local TH control in the brain by
generating the active hormone T3 from its precursor T4. Dysfunction of D2 likely
results in a neurocognitive phenotype. No mutations in D2 have been reported yet.
OBJECTIVE: The objective of the study was to identify D2 mutations in patients
with intellectual disability and to test their functional consequences. DESIGN,
SETTING, AND PATIENTS: The patients were selected from the multicenter Thyroid
Origin of Psychomotor Retardation study, which is a cohort of 946 subjects with
unexplained intellectual disability. Based on characteristic serum TH values, the
coding region of the DIO2 gene was sequenced in 387 patients. Functional
consequences were assessed by in vitro D2 assays or intact cell metabolism
studies using cells transfected with wild-type or mutant D2. RESULTS: Sequence
analysis revealed two heterozygous mutations: c.11T>A (p.L4H) in three subjects
and c.305C>T (p.T102I) in one subject. Sequence analysis of family members
revealed several carriers, but no segregation was observed with thyroid
parameters or neurocognitive phenotype. Extensive tests with different in vitro
D2 assays did not show differences between wild-type and mutant D2. CONCLUSION:
This study describes the identification and functional consequences of novel
genetic variation in TH activating enzyme D2. Family studies and functional tests
suggest that these variants do not underlie the neurocognitive impairment.
Altogether our data provide evidence of the existence of rare but apparently
harmless genetic variants of D2.
PMID- 25140403
TI - Loss of sex difference in high-density lipoprotein cholesterol in diabetic women
during acute stress.
AB - CONTEXT: The gender gap in high-density lipoprotein cholesterol (HDL-C) is well
documented in health and also maintained in diverse chronic conditions, including
menopause and diabetes. The mechanism for this difference in HDL-C and its
regulation is not well understood. We evaluated whether this gender gap is
maintained during acute stress. SETTING AND DESIGN: Diabetic patients with
metabolic decompensation (n=179) were studied in the fasting state within 24
hours of admission to hospital, and again at outpatient follow-up. Fasting lipids
and measures of glycemic control were evaluated on both occasions. The population
was predominately minority, 78% Hispanic or African American. RESULTS: During
admission, fasting lipid concentrations were not different in women (W) (n = 88)
and men (M) (n = 91); serum total cholesterol (total-C), triglycerides (TG), low
density lipoprotein cholesterol (LDL-C), and HDL-C were similar. Glycemic control
was also similar; hemoglobin A1c (A1C) and serum glucose at presentation to
hospital were not different in men and women. Compared with a subset of patients
with pre-admission data (W, 35; M, 24), a decline of HDL-C was observed, greater
in women (P = .005). At outpatient follow-up after admission, median duration
approximately 4 months in each group (P = .39), changes in TG, LDL-C, and total-C
from baseline admission were not different in men and women. In contrast, whereas
HDL-C increased in both groups, the increase (median [interquartile range]) was
significantly greater in women, 11 (4, 23) vs 6 (-1, 15) mg/dL (P < .003). This
larger increase restored the gender gap in fasting HDL-C, 48 (39, 61) and 41 (36,
49) mg/dL in women and men at follow-up (P < .002). A1C improved similarly in
each group. CONCLUSIONS: The sex difference in HDL-C levels is lost at time of
admission to hospital in patients with diabetes, and returns when acute stress
has resolved. These results raise the possibility that recurrent episodes of
acute stress may lead to cumulative loss of the HDL-C advantage in women.
PMID- 25140404
TI - Central hypoadrenalism.
AB - CONTEXT: Central hypoadrenalism is a frequent complication of pituitary and
hypothalamic pathology and is associated with increased morbidity and mortality.
Optimal exogenous glucocorticoid use is dependent on the use of appropriate
diagnostic tests and careful assessment of the clinical response to
glucocorticoid replacement therapy. EVIDENCE ACQUISITION: A PubMed search for the
terms central hypoadrenalism, ACTH deficiency, glucocorticoid suppression, and
glucocorticoid replacement was conducted; the papers identified and the
references listed were used to build a reference list. EVIDENCE SYNTHESIS: The
published literature was assessed to present a summary of the available evidence
with regard to etiology, diagnosis, and treatment of central hypoadrenalism.
CONCLUSIONS: A functional hypothalamic pituitary adrenal axis is essential for
normal health and life expectancy; its complexity presents challenges to the
clinician in the identification of patients and in the maintenance of such
patients in a glucocorticoid-sufficient state. The most common cause of central
hypoadrenalism remains exogenous glucocorticoid use. Further research in this
field should be directed toward disease prevention by minimizing glucocorticoid
exposure and toward the identification of a biomarker for glucocorticoid
sufficiency that will aid clinicians in optimizing treatment.
PMID- 25140405
TI - Choroidal tuberculoma showing paradoxical worsening in a patient with miliary TB.
AB - Tuberculosis (TB) remains an important public health problem worldwide. Ocular
involvement in patients with systemic TB has traditionally been considered
uncommon. Diagnosing ocular TB is challenging and often delayed, especially in
the absence of pulmonary signs or symptoms typical of TB. Here we describe a case
of paradoxical reaction after antituberculosis therapy in an immunocompetent
patient with ocular TB.
PMID- 25140406
TI - Differentiated availability of geochemical mercury pools controls methylmercury
levels in estuarine sediment and biota.
AB - Neurotoxic methylmercury (MeHg) formed from inorganic divalent mercury (Hg(II))
accumulates in aquatic biota and remains at high levels worldwide. It is poorly
understood to what extent different geochemical Hg pools contribute to these
levels. Here we report quantitative data on MeHg formation and bioaccumulation,
in mesocosm water-sediment model ecosystems, using five Hg(II) and MeHg isotope
tracers simulating recent Hg inputs to the water phase and Hg stored in sediment
as bound to natural organic matter or as metacinnabar. Calculations for an
estuarine ecosystem suggest that the chemical speciation of Hg(II) solid/adsorbed
phases control the sediment Hg pool's contribution to MeHg, but that input of
MeHg from terrestrial and atmospheric sources bioaccumulates to a substantially
greater extent than MeHg formed in situ in sediment. Our findings emphasize the
importance of MeHg loadings from catchment runoff to MeHg content in estuarine
biota and we suggest that this contribution has been underestimated.
PMID- 25140408
TI - Chronic alcohol administration causes expression of calprotectin and RAGE
altering the distribution of zinc ions in mouse testis.
AB - Several studies reported that chronic alcohol consumption alters the intestinal
mucosa barrier, and subsequent entrance of endotoxins into the bloodstream. In
many tissues endotoxin exposure causes the expression of calprotectin (CP) and
the receptor for advanced glycation -end products (RAGE). In this study we
investigated whether chronic alcohol administration causes expression of CP and
RAGE in mouse testis. The distribution of free and loosely bound Zn(2+) (FLB
Zn(2+)) in the testicular tissues was also evaluated. Alcohol-induced testicular
damage was documented by measuring testosterone blood levels and by light and
electron microscope studies. Twenty mice were treated daily for three weeks with
3.0 g/kg of a 25% solution of alcohol. Ten mice were treated in the same period
of time with a solution of maltose dextrins, isocaloric to alcohol. Twenty
untreated mice were used as controls. Alcohol treated mice showed diffuse
expression of CP and RAGE in the interstitial cells. RAGE was found also in the
basal compartment of the seminiferous tubules. Depletion of FLB-Zn(2+) was
observed in the adluminal compartment of the seminiferous tubules. Expression of
CP and RAGE was not found in control mice and maltose dextrin treated mice. Our
results indicated novel mechanisms by which alcohol acts in testis. Indeed, CP
and RAGE may cause the generation of oxidants and inflammatory mediators, with
negative impact on testicular functions. Depletion of FLB-Zn(2+) may contribute
to the dysregulation of spermatogenesis.
PMID- 25140407
TI - Patient Navigation in a Colorectal Cancer Screening Program.
AB - CONTEXT: Colorectal cancer (CRC) is the second leading cause of cancer death
among cancers affecting both men and women in the United States. The Centers for
Disease Control and Prevention's Colorectal Cancer Control Program (CRCCP)
supports both direct clinical screening services (screening provision) and
activities to promote screening at the population level (screening promotion).
OBJECTIVE: The purpose of this study was to characterize patient navigation (PN)
programs for screening provision and promotion for the first 1 to 2 years of
program funding. PARTICIPANTS: We conducted a cross-sectional survey of the 29
CRCCP grantees (25 states and 4 tribal organizations) and 14 in-depth interviews
to assess program implementation. MAIN OUTCOME MEASURES: The survey and interview
guide collected information on CRC screening provision and promotion activities
and PN, including the structure of the PN program, characteristics of the
navigators, funding mechanism, and navigators' activities. RESULTS: Twenty-four
of 28 CRCCP grantees of the survey used PN for screening provision whereas 18
grantees used navigation for screening promotion. Navigators were often trained
in nursing or public health. Navigation activities were similar for both
screening provision and promotion, and common tasks included assessing and
responding to patient barriers to screening, providing patient education, and
scheduling appointments. For screening provision, activities centered on making
reminder calls, educating patients on bowel preparation for colonoscopies, and
tracking patients for completion of the tests. Navigation may influence screening
quality by improving patients' bowel preparation for colonoscopies. CONCLUSIONS:
Our study provides insights into PN across a federally funded CRC program.
Results suggest that PN activities may be instrumental in recruiting people into
cancer screening and ensuring completed screening and follow-up.
PMID- 25140409
TI - The effect of melatonin on procarbazine induced testicular toxicity on rats.
AB - Procarbazine (P) is an effective chemotherapeutic drug especially used in
lymphoma treatment; however testicular toxicity is a limiting factor. Various
ways of treatment were tried to preserve testicular function including hormonal
treatment, antioxidant treatment, and sperm cryopreservation but resulted with
low rates of satisfaction. Procarbazine is a well known agent causing sterility
even in the first doses of chemotherapy. Antioxidants such as N acetylcysteine
and ascorbate have been used for protective purposes and were very successful.
Melatonin (M) is another powerful antioxidant and we aimed to use M for the
protection of P induced testicular toxicity in this study. Procarbazine was given
peroral by gavage once a week at a dose of 62.5 mg/kg/week for 4 weeks (total
dose: 250 mg/kg) (P group) and in procarbazine + melatonin (PM) group, 10 mg/kg
melatonin was intraperitoneally administered daily for five days a week for 4
weeks (total 20 days). The experiment ended at day 90. In the P and PM groups the
testicle width, length, and weight, sperm A and sperm AB properties (Sperm A:
sperms straight line progressive, Sperm B: sperms straight slow progressive,
Sperm AB: Sperm A + Sperm B), spermatogonia, Sertoli cells, seminiferous tubule,
and germinative layer thickness were lowered as compared with the control group.
However, there were no significant differences between the P and PM groups in
regard to these parameters. Melatonin preserved Sertoli cell and spermatogonia
function. The testosterone and follicle-stimulating hormone (FSH) levels were
also preserved. Melatonin significantly decreased malondialdehyde (MDA) levels
and preserved the antioxidant enzyme levels such as glutathione peroxidase (GPx)
and nitrite nitrate (NO2-/NO3-). Melatonin may protect testicular functions in P
treated patients and is open to consideration during chemotherapy since it
appears to be without any side effects.
PMID- 25140410
TI - Reversible modulation of orbital occupations via an interface-induced polar state
in metallic manganites.
AB - The breaking of orbital degeneracy on a transition metal cation and the resulting
unequal electronic occupations of these orbitals provide a powerful lever over
electron density and spin ordering in metal oxides. Here, we use ab initio
calculations to show that reversibly modulating the orbital populations on Mn
atoms can be achieved at ferroelectric/manganite interfaces by the presence of
ferroelectric polarization on the nanoscale. The change in orbital occupation can
be as large as 10%, greatly exceeding that of bulk manganites. This reversible
orbital splitting is in large part controlled by the propagation of ferroelectric
polar displacements into the interfacial region, a structural motif absent in the
bulk and unique to the interface. We use epitaxial thin film growth and scanning
transmission electron microscopy to verify this key interfacial polar distortion
and discuss the potential of reversible control of orbital polarization via
nanoscale ferroelectrics.
PMID- 25140411
TI - Two-center noninteger-n overlap, Coulomb, and kinetic energy integrals by
numerical contour integration.
AB - Numerical contour integration accurately evaluates two-center overlap, Coulomb,
and kinetic energy integrals involving noninteger-n Slater-type orbitals.
PMID- 25140412
TI - Frozen in beta.
PMID- 25140413
TI - Work and tension: new evidence that adherent cells of the same area do the same
work independent of stiffness and focal adhesions.
PMID- 25140414
TI - All that jazz coming out of my ears.
PMID- 25140415
TI - Evaluation of fluorophores to label SNAP-tag fused proteins for multicolor single
molecule tracking microscopy in live cells.
AB - Single-molecule tracking has become a widely used technique for studying protein
dynamics and their organization in the complex environment of the cell. In
particular, the spatiotemporal distribution of membrane receptors is an active
field of study due to its putative role in the regulation of signal transduction.
The SNAP-tag is an intrinsically monovalent and highly specific genetic tag for
attaching a fluorescent label to a protein of interest. Little information is
currently available on the choice of optimal fluorescent dyes for single-molecule
microscopy utilizing the SNAP-tag labeling system. We surveyed 6 green and 16 red
excitable dyes for their suitability in single-molecule microscopy of SNAP-tag
fusion proteins in live cells. We determined the nonspecific binding levels and
photostability of these dye conjugates when bound to a SNAP-tag fused membrane
protein in live cells. We found that only a limited subset of the dyes tested is
suitable for single-molecule tracking microscopy. The results show that a careful
choice of the dye to conjugate to the SNAP-substrate to label SNAP-tag fusion
proteins is very important, as many dyes suffer from either rapid photobleaching
or high nonspecific staining. These characteristics appear to be unpredictable,
which motivated the need to perform the systematic survey presented here. We have
developed a protocol for evaluating the best dyes, and for the conditions that we
evaluated, we find that Dy 549 and CF 640 are the best choices tested for single
molecule tracking. Using an optimal dye pair, we also demonstrate the possibility
of dual-color single-molecule imaging of SNAP-tag fusion proteins. This survey
provides an overview of the photophysical and imaging properties of a range of
SNAP-tag fluorescent substrates, enabling the selection of optimal dyes and
conditions for single-molecule imaging of SNAP-tagged fusion proteins in
eukaryotic cell lines.
PMID- 25140416
TI - An active oscillator model describes the statistics of spontaneous otoacoustic
emissions.
AB - Even in the absence of external stimulation, the cochleas of most humans emit
very faint sounds below the threshold of hearing, sounds that are known as
spontaneous otoacoustic emissions. They are a signature of the active
amplification mechanism in the cochlea. Emissions occur at frequencies that are
unique for an individual and change little over time. The statistics of a
population of ears exhibit characteristic features such as a preferred relative
frequency distance between emissions (interemission intervals). We propose a
simplified cochlea model comprising an array of active nonlinear oscillators
coupled both hydrodynamically and viscoelastically. The oscillators are subject
to a weak spatial disorder that lends individuality to the simulated cochlea. Our
model captures basic statistical features of the emissions: distributions of 1),
emission frequencies; 2), number of emissions per ear; and 3), interemission
intervals. In addition, the model reproduces systematic changes of the
interemission intervals with frequency. We show that the mechanism for the
preferred interemission interval in our model is the occurrence of synchronized
clusters of oscillators.
PMID- 25140417
TI - Geometry regulates traction stresses in adherent cells.
AB - Cells generate mechanical stresses via the action of myosin motors on the actin
cytoskeleton. Although the molecular origin of force generation is well
understood, we currently lack an understanding of the regulation of force
transmission at cellular length scales. Here, using 3T3 fibroblasts, we
experimentally decouple the effects of substrate stiffness, focal adhesion
density, and cell morphology to show that the total amount of work a cell does
against the substrate to which it is adhered is regulated by the cell spread area
alone. Surprisingly, the number of focal adhesions and the substrate stiffness
have little effect on regulating the work done on the substrate by the cell. For
a given spread area, the local curvature along the cell edge regulates the
distribution and magnitude of traction stresses to maintain a constant strain
energy. A physical model of the adherent cell as a contractile gel under a
uniform boundary tension and mechanically coupled to an elastic substrate
quantitatively captures the spatial distribution and magnitude of traction
stresses. With a single choice of parameters, this model accurately predicts the
cell's mechanical output over a wide range of cell geometries.
PMID- 25140418
TI - Single-molecule tracking of inositol trisphosphate receptors reveals different
motilities and distributions.
AB - Puffs are local Ca(2+) signals that arise by Ca(2+) liberation from the
endoplasmic reticulum through the concerted opening of tightly clustered inositol
trisphosphate receptors/channels (IP3Rs). The locations of puff sites observed by
Ca(2+) imaging remain static over several minutes, whereas fluorescence recovery
after photobleaching (FRAP) experiments employing overexpression of fluorescently
tagged IP3Rs have shown that the majority of IP3Rs are freely motile. To address
this discrepancy, we applied single-molecule imaging to locate and track type 1
IP3Rs tagged with a photoswitchable fluorescent protein and expressed in COS-7
cells. We found that ~ 70% of the IP3R1 molecules were freely motile, undergoing
random walk motility with an apparent diffusion coefficient of ~ 0.095 MUm s(-1),
whereas the remaining molecules were essentially immotile. A fraction of the
immotile IP3Rs were organized in clusters, with dimensions (a few hundred
nanometers across) comparable to those previously estimated for the IP3R clusters
underlying functional puff sites. No short-term (seconds) changes in overall
motility or in clustering of immotile IP3Rs were apparent following activation of
IP3/Ca(2+) signaling. We conclude that stable clusters of small numbers of
immotile IP3Rs may underlie local Ca(2+) release sites, whereas the more numerous
motile IP3Rs appear to be functionally silent.
PMID- 25140419
TI - Quantitation of malaria parasite-erythrocyte cell-cell interactions using optical
tweezers.
AB - Erythrocyte invasion by Plasmodium falciparum merozoites is an essential step for
parasite survival and hence the pathogenesis of malaria. Invasion has been
studied intensively, but our cellular understanding has been limited by the fact
that it occurs very rapidly: invasion is generally complete within 1 min, and
shortly thereafter the merozoites, at least in in vitro culture, lose their
invasive capacity. The rapid nature of the process, and hence the narrow time
window in which measurements can be taken, have limited the tools available to
quantitate invasion. Here we employ optical tweezers to study individual invasion
events for what we believe is the first time, showing that newly released P.
falciparum merozoites, delivered via optical tweezers to a target erythrocyte,
retain their ability to invade. Even spent merozoites, which had lost the ability
to invade, retain the ability to adhere to erythrocytes, and furthermore can
still induce transient local membrane deformations in the erythrocyte membrane.
We use this technology to measure the strength of the adhesive force between
merozoites and erythrocytes, and to probe the cellular mode of action of known
invasion inhibitory treatments. These data add to our understanding of the
erythrocyte-merozoite interactions that occur during invasion, and demonstrate
the power of optical tweezers technologies in unraveling the blood-stage biology
of malaria.
PMID- 25140420
TI - Mechanical detection of a long-range actin network emanating from a biomimetic
cortex.
AB - Actin is ubiquitous globular protein that polymerizes into filaments and forms
networks that participate in the force generation of eukaryotic cells. Such
forces are used for cell motility, cytokinesis, and tissue remodeling. Among
those actin networks, we focus on the actin cortex, a dense branched network
beneath the plasma membrane that is of particular importance for the mechanical
properties of the cell. Here we reproduce the cellular cortex by activating actin
filament growth on a solid surface. We unveil the existence of a sparse actin
network that emanates from the surface and extends over a distance that is at
least 10 times larger than the cortex itself. We call this sparse actin network
the "actin cloud" and characterize its mechanical properties with optical
tweezers. We show, both experimentally and theoretically, that the actin cloud is
mechanically relevant and that it should be taken into account because it can
sustain forces as high as several picoNewtons (pN). In particular, it is known
that in plant cells, actin networks similar to the actin cloud have a role in
positioning the nucleus; in large oocytes, they play a role in driving chromosome
movement. Recent evidence shows that such networks even prevent granule
condensation in large cells.
PMID- 25140421
TI - Actin-myosin spatial patterns from a simplified isotropic viscoelastic model.
AB - F-actin networks are involved in cell mechanical processes ranging from motility
to endocytosis. The mesoscale architecture of assemblies of individual F-actin
polymers that gives rise to micrometer-scale rheological properties is poorly
understood, despite numerous in vivo and vitro studies. In vitro networks have
been shown to organize into spatial patterns when spatially confined, including
dense spherical shells inside spherical emulsion droplets. Here we develop a
simplified model of an isotropic, compressible, viscoelastic material continually
assembling and disassembling. We demonstrate that spherical shells emerge
naturally when the strain relaxation rate (corresponding to internal network
reorganization) is slower than the disassembly rate (corresponding to F-actin
depolymerization). These patterns are consistent with recent experiments,
including a collapse of shells to a central high-density focus of F-actin when
either assembly or disassembly is reduced with drugs. Our results demonstrate how
complex spatio-temporal patterns can emerge without spatially distributed force
generation, polar alignment of F-actin polymers, or spatially nonuniform
regulation of F-actin by upstream biochemical networks.
PMID- 25140422
TI - Osmotic pressure in a bacterial swarm.
AB - Using Escherichia coli as a model organism, we studied how water is recruited by
a bacterial swarm. A previous analysis of trajectories of small air bubbles
revealed a stream of fluid flowing in a clockwise direction ahead of the swarm. A
companion study suggested that water moves out of the agar into the swarm in a
narrow region centered ~ 30 MUm from the leading edge of the swarm and then back
into the agar (at a smaller rate) in a region centered ~ 120 MUm back from the
leading edge. Presumably, these flows are driven by changes in osmolarity. Here,
we utilized green/red fluorescent liposomes as reporters of osmolarity to verify
this hypothesis. The stream of fluid that flows in front of the swarm contains
osmolytes. Two distinct regions are observed inside the swarm near its leading
edge: an outer high-osmolarity band (~ 30 mOsm higher than the agar baseline) and
an inner low-osmolarity band (isotonic or slightly hypotonic to the agar
baseline). This profile supports the fluid-flow model derived from the drift of
air bubbles and provides new (to our knowledge) insights into water maintenance
in bacterial swarms. High osmotic pressure at the leading edge of the swarm
extracts water from the underlying agar and promotes motility. The osmolyte is of
high molecular weight and probably is lipopolysaccharide.
PMID- 25140424
TI - Orientational ordering of carotenoids in myelin membranes resolved by polarized
Raman microspectroscopy.
AB - We study orientational ordering of membrane compounds in the myelinated nerve
fiber by means of polarized Raman microspectroscopy. The theory of orientational
distribution functions was adapted to live-cell measurements. The obtained
orientational distribution functions of carotenoids and lipid acyl chain clearly
indicated a predominantly radial-like orientation in membranes of the myelin. Two
dimensional Raman images, made under optimal polarization of incident laser beam,
corroborated the proposed carotenoid orientation within the bilayer. Experimental
data suggested the tilted orientation of both carotenoid polyenic and lipid acyl
chains. The values of maximum tilt angles were similar, with possible implication
of carotenoid-induced ordering effect on lipid acyl chains, and hence change of
myelin membrane properties. This study stages carotenoids of the nerve as
possible mediators of excitation and leverages underlying activity-dependent
membrane reordering.
PMID- 25140423
TI - Interplay of packing and flip-flop in local bilayer deformation. How
phosphatidylglycerol could rescue mitochondrial function in a cardiolipin
deficient yeast mutant.
AB - In a previous work, we have shown that a spatially localized transmembrane pH
gradient, produced by acid micro-injection near the external side of cardiolipin
containing giant unilamellar vesicles, leads to the formation of tubules that
retract after the dissipation of this gradient. These tubules have morphologies
similar to mitochondrial cristae. The tubulation effect is attributable to direct
phospholipid packing modification in the outer leaflet, that is promoted by
protonation of cardiolipin headgroups. In this study, we compare the case of
cardiolipin-containing giant unilamellar vesicles with that of giant unilamellar
vesicles that contain phosphatidylglycerol (PG). Local acidification also
promotes formation of tubules in the latter. However, compared with cardiolipin
containing giant unilamellar vesicles the tubules are longer, exhibit a visible
pearling, and have a much longer lifetime after acid micro-injection is stopped.
We attribute these differences to an additional mechanism that increases
monolayer surface imbalance, namely inward PG flip-flop promoted by the local
transmembrane pH gradient. Simulations using a fully nonlinear membrane model as
well as geometrical calculations are in agreement with this hypothesis.
Interestingly, among yeast mutants deficient in cardiolipin biosynthesis, only
the crd1-null mutant, which accumulates phosphatidylglycerol, displays
significant mitochondrial activity. Our work provides a possible explanation of
such a property and further emphasizes the salient role of specific lipids in
mitochondrial function.
PMID- 25140425
TI - Membrane interactions of phylloseptin-1, -2, and -3 peptides by oriented solid
state NMR spectroscopy.
AB - Phylloseptin-1, -2, and -3 are three members of the family of linear cationic
antimicrobial peptides found in tree frogs. The highly homologous peptides
encompass 19 amino acids, and only differ in the amino acid composition and
charge at the six most carboxy-terminal residues. Here, we investigated how such
subtle changes are reflected in their membrane interactions and how these can be
correlated to their biological activities. To this end, the three peptides were
labeled with stable isotopes, reconstituted into oriented phospholipid bilayers,
and their detailed topology determined by a combined approach using (2)H and
(15)N solid-state NMR spectroscopy. Although phylloseptin-2 and -3 adopt perfect
in-plane alignments, the tilt angle of phylloseptin-1 deviates by 8 degrees
probably to assure a more water exposed localization of the lysine-17 side chain.
Furthermore, different azimuthal angles are observed, positioning the amphipathic
helices of all three peptides with the charged residues well exposed to the water
phase. Interestingly, our studies also reveal that two orientation-dependent (2)H
quadrupolar splittings from methyl-deuterated alanines and one (15)N amide
chemical shift are sufficient to unambiguously determine the topology of
phylloseptin-1, where quadrupolar splittings close to the maximum impose the most
stringent angular restraints. As a result of these studies, a strategy is
proposed where the topology of a peptide structure can be determined accurately
from the labeling with (15)N and (2)H isotopes of only a few amino acid residues.
PMID- 25140426
TI - Influenza A matrix protein M1 multimerizes upon binding to lipid membranes.
AB - The matrix protein M1 plays a pivotal role in the budding of influenza virus from
the plasma membrane (PM) of infected cells. This protein interacts with viral
genetic material and envelope proteins while binding to the inner leaflet of the
PM. Its oligomerization is therefore closely connected to the assembly of viral
components and the formation of new virions. Of interest, the molecular details
of M1 interaction with lipids and other viral proteins are far from being
understood, and it remains to be determined whether the multimerization of M1 is
affected by its binding to the PM and interaction with its components. To clarify
the connection between M1 oligomerization and binding to lipid membranes, we
applied a combination of several quantitative microscopy approaches. First, we
used number and brightness (N&B) microscopy to characterize protein
multimerization upon interaction with the PM of living cells. Second, we used
controlled biophysical models of the PM (i.e., supported bilayers) to delve into
the details of M1-lipid and M1-M1 interactions by employing a combination of
raster image correlation spectroscopy (RICS), fluorescence correlation
spectroscopy (FCS), and atomic force microscopy (AFM). Our results show that M1
oligomer formation is strongly enhanced by membrane binding and does not
necessarily require the presence of other viral proteins. Furthermore, we propose
a specific model to explain M1 binding to the lipid bilayer and the formation of
multimers.
PMID- 25140427
TI - Temperature and electrolyte optimization of the alpha-hemolysin latch sensing
zone for detection of base modification in double-stranded DNA.
AB - The latch region of the wild-type protein pore alpha-hemolysin (alpha-HL)
constitutes a sensing zone for individual abasic sites (and furan analogs) in
double-stranded DNA (dsDNA). The presence of an abasic site or furan within a DNA
duplex, electrophoretically captured in the alpha-HL vestibule and positioned at
the latch region, can be detected based on the current blockage prior to duplex
unzipping. We investigated variations in blockage current as a function of
temperature (12-35 degrees C) and KCl concentration (0.15-1.0 M) to understand
the origin of the current signature and to optimize conditions for identifying
the base modification. In 1 M KCl solution, substitution of a furan for a
cytosine base in the latch region results in an ~ 8 kJ mol(-1) decrease in the
activation energy for ion transport through the protein pore. This corresponds to
a readily measured ~ 2 pA increase in current at room temperature. Optimal
resolution for detecting the presence of a furan in the latch region is achieved
at lower KCl concentrations, where the noise in the measured blockage current is
significantly lower. The noise associated with the blockage current also depends
on the stability of the duplex (as measured from the melting temperature), where
a greater noise in the measured blockage current is observed for less stable
duplexes.
PMID- 25140428
TI - Azobenzene photoisomerization-induced destabilization of B-DNA.
AB - Molecular photoswitches provide a promising way for selective regulation of
nanoscaled biological systems. It has been shown that conformational changes of
azobenzene, one of the widely used photoswitches, can be used to reversibly
control DNA duplex formation. Here, we investigate the conformational response of
DNA upon azobenzene binding and isomerization, using a threoninol linker that has
been experimentally investigated recently. To this end, nonequilibrium molecular
dynamics simulations are carried out using a switching potential describing the
photoinduced isomerization. Attachment of azobenzene leads to a distortion of the
DNA helical conformation that is similar for the trans and cis forms. However,
the trans form is stabilized by favorable stacking interactions whereas the cis
form is found to remain flipped out of the basepair-stacked position. Multiple
azobenzene attachment augments the distortion in DNA helical conformation. The
distorted DNA retains nativelike pairing of bases at ambient temperatures, but
shows weaker basepairing compared to native DNA at an elevated temperature.
PMID- 25140429
TI - Insights into the structure and dynamics of measles virus nucleocapsids by 1H
detected solid-state NMR.
AB - (1)H-detected solid-state nuclear magnetic resonance (NMR) experiments are
recorded on both intact and trypsin-cleaved sedimented measles virus (MeV)
nucleocapsids under ultra-fast magic-angle spinning. High-resolution (1)H,(15)N
fingerprints allow probing the degree of molecular order and flexibility of
individual capsid proteins, providing an exciting atomic-scale complement to
electro microscopy (EM) studies of the same systems.
PMID- 25140430
TI - Complex pathways in folding of protein G explored by simulation and experiment.
AB - The B1 domain of protein G has been a classic model system of folding for
decades, the subject of numerous experimental and computational studies. Most of
the experimental work has focused on whether the protein folds via an
intermediate, but the evidence is mostly limited to relatively slow kinetic
observations with a few structural probes. In this work we observe folding on the
submillisecond timescale with microfluidic mixers using a variety of probes
including tryptophan fluorescence, circular dichroism, and photochemical
oxidation. We find that each probe yields different kinetics and compare these
observations with a Markov State Model constructed from large-scale molecular
dynamics simulations and find a complex network of states that yield different
kinetics for different observables. We conclude that there are many folding
pathways before the final folding step and that these paths do not have large
free energy barriers.
PMID- 25140431
TI - Characterization of protein flexibility using small-angle x-ray scattering and
amplified collective motion simulations.
AB - Large-scale flexibility within a multidomain protein often plays an important
role in its biological function. Despite its inherent low resolution, small-angle
x-ray scattering (SAXS) is well suited to investigate protein flexibility and
determine, with the help of computational modeling, what kinds of protein
conformations would coexist in solution. In this article, we develop a tool that
combines SAXS data with a previously developed sampling technique called
amplified collective motions (ACM) to elucidate structures of highly dynamic
multidomain proteins in solution. We demonstrate the use of this tool in two
proteins, bacteriophage T4 lysozyme and tandem WW domains of the formin-binding
protein 21. The ACM simulations can sample the conformational space of proteins
much more extensively than standard molecular dynamics (MD) simulations.
Therefore, conformations generated by ACM are significantly better at reproducing
the SAXS data than are those from MD simulations.
PMID- 25140432
TI - Molecular basis of the mechanical hierarchy in myomesin dimers for sarcomere
integrity.
AB - Myomesin is one of the most important structural molecules constructing the M
band in the force-generating unit of striated muscle, and a critical structural
maintainer of the sarcomere. Using molecular dynamics simulations, we here
dissect the mechanical properties of the structurally known building blocks of
myomesin, namely alpha-helices, immunoglobulin (Ig) domains, and the dimer
interface at myomesin's 13th Ig domain, covering the mechanically important C
terminal part of the molecule. We find the interdomain alpha-helices to be
stabilized by the hydrophobic interface formed between the N-terminal half of
these helices and adjacent Ig domains, and, interestingly, to show a rapid
unfolding and refolding equilibrium especially under low axial forces up to ~ 15
pN. These results support and yield atomic details for the notion of recent
atomic-force microscopy experiments, namely, that the unique helices inserted
between Ig domains in myomesin function as elastomers and force buffers. Our
results also explain how the C-terminal dimer of two myomesin molecules is
mechanically outperforming the helices and Ig domains in myomesin and elsewhere,
explaining former experimental findings. This study provides a fresh view onto
how myomesin integrates elastic helices, rigid immunoglobulin domains, and an
extraordinarily resistant dimer into a molecular structure, to feature a
mechanical hierarchy that represents a firm and yet extensible molecular anchor
to guard the stability of the sarcomere.
PMID- 25140433
TI - Dynamical phase transitions reveal amyloid-like states on protein folding
landscapes.
AB - Developing an understanding of protein misfolding processes presents a crucial
challenge for unlocking the mysteries of human disease. In this article, we
present our observations of beta-sheet-rich misfolded states on a number of
protein dynamical landscapes investigated through molecular dynamics simulation
and Markov state models. We employ a nonequilibrium statistical mechanical theory
to identify the glassy states in a protein's dynamics, and we discuss the
nonnative, beta-sheet-rich states that play a distinct role in the slowest
dynamics within seven protein folding systems. We highlight the fundamental
similarity between these states and the amyloid structures responsible for many
neurodegenerative diseases, and we discuss potential consequences for mechanisms
of protein aggregation and intermolecular amyloid formation.
PMID- 25140434
TI - Functional dynamics of hexameric helicase probed by hydrogen exchange and
simulation.
AB - The biological function of large macromolecular assemblies depends on their
structure and their dynamics over a broad range of timescales; for this reason,
it is a significant challenge to investigate these assemblies using conventional
experimental techniques. One of the most promising experimental techniques is
hydrogen-deuterium exchange detected by mass spectrometry. Here, we describe to
our knowledge a new computational method for quantitative interpretation of
deuterium exchange kinetics and apply it to a hexameric viral helicase P4 that
unwinds and translocates RNA into a virus capsid at the expense of ATP
hydrolysis. Room-temperature dynamics probed by a hundred nanoseconds of all-atom
molecular dynamics simulations is sufficient to predict the exchange kinetics of
most sequence fragments and provide a residue-level interpretation of the low
resolution experimental results. The strategy presented here is also a valuable
tool to validate experimental data, e.g., assignments, and to probe mechanisms
that cannot be observed by x-ray crystallography, or that occur over timescales
longer than those that can be realistically simulated, such as the opening of the
hexameric ring.
PMID- 25140436
TI - Passive mechanical forces control cell-shape change during Drosophila ventral
furrow formation.
AB - During Drosophila gastrulation, the ventral mesodermal cells constrict their
apices, undergo a series of coordinated cell-shape changes to form a ventral
furrow (VF) and are subsequently internalized. Although it has been well
documented that apical constriction is necessary for VF formation, the mechanism
by which apical constriction transmits forces throughout the bulk tissue of the
cell remains poorly understood. In this work, we develop a computational vertex
model to investigate the role of the passive mechanical properties of the
cellular blastoderm during gastrulation. We introduce to our knowledge novel data
that confirm that the volume of apically constricting cells is conserved
throughout the entire course of invagination. We show that maintenance of this
constant volume is sufficient to generate invagination as a passive response to
apical constriction when it is combined with region-specific elasticities in the
membranes surrounding individual cells. We find that the specific sequence of
cell-shape changes during VF formation is critically controlled by the stiffness
of the lateral and basal membrane surfaces. In particular, our model demonstrates
that a transition in basal rigidity is sufficient to drive VF formation along the
same sequence of cell-shape change that we observed in the actual embryo, with no
active force generation required other than apical constriction.
PMID- 25140435
TI - Induction of peptide bond dipoles drives cooperative helix formation in the
(AAQAA)3 peptide.
AB - Cooperativity is a central feature in the formation of secondary structures in
proteins. However, the driving forces behind this cooperativity are poorly
understood. The present work shows that the cooperativity of helix formation in
the acetyl-(AAQAA)3-NH2 peptide is significantly enhanced using an empirical
force field that explicitly includes the treatment of electronic polarizability.
Polarizable simulations yield helical content consistent with experimental
measurements and indicate that the dependence of helical content on temperature
is improved over additive models, though further sampling is required to fully
validate this conclusion. Cooperativity is indicated by the peptide sampling
either the coiled state or long helices with relatively low populations of short
helices. The cooperativity is shown to be associated with enhanced dipole moments
of the peptide backbone upon helix formation. These results indicate the
polarizable force field to more accurately model peptide-folding cooperativity
based on its physically realistic treatment of electronic polarizability.
PMID- 25140437
TI - RNA-based regulation: dynamics and response to perturbations of competing RNAs.
AB - The observation that, through a titration mechanism, microRNAs (miRNAs) can act
as mediators of effective interactions among their common targets (competing
endogenous RNAs or ceRNAs) has brought forward the idea (i.e., the ceRNA
hypothesis) that RNAs can regulate each other in extended cross-talk networks.
Such an ability might play a major role in posttranscriptional regulation to
shape a cell's protein repertoire. Recent work focusing on the emergent
properties of the cross-talk networks has emphasized the high flexibility and
selectivity that may be achieved at stationarity. On the other hand, dynamical
aspects, possibly crucial on the relevant timescales, are far less clear. We have
carried out a dynamical study of the ceRNA hypothesis on a model of
posttranscriptional regulation. Sensitivity analysis shows that ceRNA cross-talk
is dynamically extended, i.e., it may take place on timescales shorter than those
required to achieve stationarity even in cases where no cross-talk occurs in the
steady state, and is possibly amplified. In addition, in the case of large,
transfection-like perturbations, the system may develop a strongly nonlinear,
threshold response. Finally, we show that the ceRNA effect provides a very
efficient way for a cell to achieve fast positive shifts in the level of a ceRNA
when necessary. These results indicate that competition for miRNAs may indeed
provide an elementary mechanism to achieve system-level regulatory effects on the
transcriptome over physiologically relevant timescales.
PMID- 25140438
TI - The interrelations among stochastic pacing, stability, and memory in the heart.
AB - Low pacing variability in the heart has been clinically reported as a risk factor
for lethal cardiac arrhythmias and arrhythmic death. In ia previous simulation
study, we demonstrated that stochastic pacing sustains an antiarrhythmic effect
by moderating the slope of the action potential duration (APD) restitution curve,
by reducing the propensity of APD alternans, converting discordant to concordant
alternans, and ultimately preventing wavebreaks. However, the dynamic mechanisms
relating pacing stochasticity to tissue stability are not yet known. In this
work, we develop a mathematical framework to describe the APD signal using an
autoregressive stochastic model, and we establish the interrelations between
stochastic pacing, cardiac memory, and cardiac stability, as manifested by the
degree of APD alternans. Employing stability analysis tools, we show that
increased stochasticity in the ventricular tissue activation sequence works to
lower the maximal absolute eigenvalues of the stochastic model, thereby
contributing to increased stability. We also show that the memory coefficients of
the autoregressive model are modulated by pacing stochasticity in a nonlinear,
biphasic way, so that for exceedingly high levels of pacing stochasticity, the
antiarrhythmic effect is hampered by increasing APD variance. This work may
contribute to establishment of an optimal antiarrhythmic pacing protocol in a
future study.
PMID- 25140439
TI - Evaluating complex interventions: perspectives and issues for health behaviour
change interventions.
AB - OBJECTIVE: Health behaviour change interventions (HBCIs), used in health
education, health promotion, patient education and psychotherapy areas, are
considered complex interventions. The objective of this article is to discuss the
value and limitations of using randomised clinical trials (RCTs) to asses HBCIs.
METHODS: A scoping review of the literature was conducted to identify the main
challenges of using RCTs for evaluating HBCIs. The issues were illustrated by
case studies selected from research conducted by our multidisciplinary team.
RESULTS: In complex interventions, effects are produced not only by the
intervention, but are strongly linked to context. Issues relating to
transferability of results are therefore critical, and require adjustments to the
RCT model. Sampling bias, biases related to the experimental conditions and
biases due to the absence of double-blindness were examined and illustrated by
case studies. CONCLUSION: The results underline the importance of a
multidisciplinary approach. They call for adapted or alternative evaluation
models that overcome the limitations of RCTs.
PMID- 25140440
TI - Lattice model for silica polymerization: Monte Carlo simulations of the
transition between gel and nanoparticle phases.
AB - We present Monte Carlo simulations of a lattice model describing silica
polymerization with an emphasis on the transition between gel states and
nanoparticle states as the pH and silica concentration are varied. The pH in the
system is controlled by the addition of a structure-directing agent (SDA) of the
type SDA(+)(OH(-)). The silica units are represented by corner-sharing tetrahedra
on a body-centered cubic lattice and the SDA(+) species by single sites with near
neighbor repulsions. We focus on two systems: one with a low silica concentration
with composition comparable to that of the clear solution silicalite-1 zeolite
synthesis and a high silica concentration system that leads to gel states. In the
dilute system, clusters have a core-shell structure, with the core predominantly
comprised of silica with some SDA(+) cations, surrounded by a shell of only
SDA(+) cations. Moreover, the average cluster size gradually decreases from 2 to
1.6 nm with increasing pH. The concentrated system forms a gel that remains
stable to increasing pH up to about 9.2. At pH values in the range of 9.2-10, the
gel transforms to nanoparticles of size around 1.0 nm, surprisingly smaller than
those in the dilute system. We also study the evolution of the Q(n) distribution
(a measure of the silica network structure) for both systems and obtain good
agreement with (29)Si NMR data available for the concentrated system.
PMID- 25140441
TI - Guillain-Barre syndrome associated with Japanese encephalitis virus infection in
China.
AB - Abstract Guillain-Barre syndrome (GBS) is preceded by an infection in about two
thirds of patients. However, the infectious organism is often not identified. GBS
secondary to Japanese encephalitis virus (JEV) infection has been reported only
in India. Herein, we report a case of GBS preceded by JEV infection in China. A
23-year-old male had generalized weakness, numbness in the extremities, and
bilateral facial nerve paralysis. One week prior, he had a high fever with
headache, and several days later, he developed facial diplegia and sensory
disturbances. Physical examination revealed facial diplegia and a weak gag
reflex, quadriparesis more pronounced distally, generalized hyporeflexia, and no
Babinski sign. JEV IgM and hepatitis B surface antibody (HbsAb) tests were
positive. Other tests for hepatitis B infection were negative. Nerve
electrophysiology suggested an acute demyelinating sensorimotor
polyradiculoneuropathy. His cerebrospinal fluid was clear, the leukocyte count
was 5 * 10(6)/L (normal range: 0-5 * 10(6)/L), protein 0.62 g/L (normal range:
0.15-0.45 g/L), and JEV IgM was weakly positive. He was diagnosed with GBS
associated with a recent JEV infection. Intravenous (IV) immunoglobulins combined
with IV methylprednisone was administered for 5 days, and at the 3-month follow
up, a complete neurological recovery was noted. GBS may be associated with JEV
infection. GBS exhibits a good response to intravenous immunoglobulin or plasma
exchange and has a good prognosis making prompt diagnosis important.
PMID- 25140442
TI - Structural study of the apatite Nd8Sr2Si6O26 by Laue neutron diffraction and
single-crystal Raman spectroscopy.
AB - A single-crystal structure determination of Nd8Sr2Si6O26 apatite, a prototype
intermediate-temperature electrolyte for solid oxide fuel cells grown by the
floating-zone method, was completed using the combination of Laue neutron
diffraction and Raman spectroscopy. While neutron diffraction was in good
agreement with P63/m symmetry, the possibility of P63 could not be convincingly
excluded. This ambiguity was removed by the collection of orientation-dependent
Raman spectra that could only be consistent with P63/m. The composition of
Nd8Sr2Si6O26 was independently verified by powder X-ray diffraction in
combination with electron probe microanalysis, with the latter confirming a
homogeneous distribution of Sr and the absence of chemical zonation commonly
observed in apatites. This comprehensive crystallochemical description of
Nd8Sr2Si6O26 provides a baseline to quantify the efficacy of cation vacancies,
oxygen superstoichiometry, and symmetry modification for promoting oxygen-ion
mobility.
PMID- 25140443
TI - DddD is a CoA-transferase/lyase producing dimethyl sulfide in the marine
environment.
AB - Dimethyl sulfide (DMS) is produced in oceans in vast amounts (>10(7) tons/year)
and mediates a wide range of processes from regulating marine life forms to cloud
formation. Nonetheless, none of the enzymes that produce DMS from
dimethylsulfoniopropionate (DMSP) has been adequately characterized. We describe
the expression and purification of DddD from the marine bacterium Marinomonas sp.
MWYL1 and its biochemical characterization. We identified DMSP and acetyl
coenzyme A to be DddD's native substrates and Asp602 as the active site residue
mediating the CoA-transferase prior to lyase activity. These findings shed light
on the biochemical utilization of DMSP in the marine environment.
PMID- 25140444
TI - The use of a mobile assistant learning system for health education based on
project-based learning.
AB - With the development of mobile devices and wireless technology, mobile technology
has gradually infiltrated nursing practice courses to facilitate instruction.
Mobile devices save manpower and reduce errors while enhancing nursing students'
professional knowledge and skills. To achieve teaching objectives and address the
drawbacks of traditional education, this study presents a mobile assistant
learning system to help nursing students prepare health education materials. The
proposed system is based on a project-based learning strategy to assist nursing
students with internalizing professional knowledge and developing critical
thinking skills. Experimental results show that the proposed mobile system and
project-based learning strategy can promote learning effectiveness and
efficiency. Most nursing students and nursing educators showed positive attitudes
toward this mobile learning system and looked forward to using it again in
related courses in the future.
PMID- 25140445
TI - Creation of a virtual triage exercise: an interprofessional communication
strategy.
AB - Virtual reality simulation as a teaching method is gaining increased acceptance
and presence in institutions of higher learning. This study presents an
innovative strategy using the interdisciplinary development of a nonimmersive
virtual reality simulation to facilitate interprofessional communication. The
purpose of this pilot project was to describe nursing students' attitudes related
to interprofessional communication following the collaborative development of a
disaster triage virtual reality simulation. Collaboration between and among
professionals is integral in enhancing patient outcomes. In addition, ineffective
communication is linked to detrimental patient outcomes, especially during times
of high stress. Poor communication has been identified as the root cause of the
majority of negative sentinel events occurring in hospitals. The simulation
development teaching model proved useful in fostering interprofessional
communication and mastering course content. Mean scores on the KidSIM Attitudes
Towards Teamwork in Training Undergoing Designed Educational Simulation survey
demonstrated that nursing students, after simulation experience,had agreement to
strong agreement inall areas surveyed including interprofessional education,
communication, roles and responsibilities of team members, and situational
awareness. The findings indicate that students value interprofessional teamwork
and the opportunity to work with other disciplines.
PMID- 25140446
TI - Cucurbitane glycosides derived from mogroside IIE: structure-taste relationships,
antioxidant activity, and acute toxicity.
AB - Mogroside IIE is a bitter triterpenoid saponin which is the main component of
unripe Luo Han Guo fruit and a precursor of the commercially available sweetener
mogroside V. In this study, we developed an enzymatic glycosyl transfer method,
by which bitter mogroside IIE could be converted into a sweet triterpenoid
saponin mixture. The reactant concentration, temperature, pH and buffer system
were studied. New saponins with the alpha-glucose group were isolated from the
resulting mixtures, and the structures of three components of the extract were
determined. The structure-taste relationships of these derivatives were also
studied together with those of the natural mogrosides. The number and
stereoconfiguration of glucose groups present in the mogroside molecules were
found to be the main factor to determine the sweet or bitter taste of a compound.
The antioxidant and food safety properties were initially evaluated by their
radical scavenging ability and via 7 day mice survival tests, respectively. The
results showed that the sweet triterpenoid saponin mixture has the same favorable
physiological and safety characteristics as the natural mogrosides.
PMID- 25140447
TI - Oligo-carrageenan kappa-induced reducing redox status and activation of TRR/TRX
system increase the level of indole-3-acetic acid, gibberellin A3 and trans
zeatin in Eucalyptus globulus trees.
AB - Eucalyptus globulus trees treated with oligo-carrageenan (OC) kappa showed an
increase in NADPH, ascorbate and glutathione levels and activation of the
thioredoxin reductase (TRR)/thioredoxin (TRX) system which enhance
photosynthesis, basal metabolism and growth. In order to analyze whether the
reducing redox status and the activation of thioredoxin reductase
(TRR)/thioredoxin (TRX) increased the level of growth-promoting hormones, trees
were treated with water (control), with OC kappa, or with inhibitors of ascorbate
synthesis, lycorine, glutathione synthesis, buthionine sulfoximine (BSO), NADPH
synthesis, CHS-828, and thioredoxin reductase activity, auranofine, and with OC
kappa, and cultivated for four additional months. Eucalyptus trees treated with
OC kappa showed an increase in the levels of the auxin indole 3-acetic acid
(IAA), gibberellin A3 (GA3) and the cytokinin trans-zeatin (t-Z) as well as a
decrease in the level of the brassinosteroid epi-brassinolide (EB). In addition,
treatment with lycorine, BSO, CHS-828 and auranofine inhibited the increase in
IAA, GA3 and t-Z as well as the decrease in EB levels. Thus, the reducing redox
status and the activation of TRR/TRX system induced by OC kappa increased the
levels of IAA, GA3 and t-Z levels determining, at least in part, the stimulation
of growth in Eucalyptus trees.
PMID- 25140448
TI - Identification of two novel alpha1-AR agonists using a high-throughput screening
model.
AB - alpha1-Adrenoceptors (ARs; 1A, 1B, and 1D) have been determined to perform
different prominent functions in the physiological responses of the sympathetic
nervous system. A high-throughput screening assay (HTS) was set up to detect
alpha1-AR subtype-selective agonists by a dual-luciferase reporter assay in
HEK293 cells. Using the HTS assay, two novel compounds, CHE3 and CHK3, were
discovered as alpha1-ARs agonists in alpha1-ARs expressed in HEK293 cells. These
compounds also showed moderate/weak anti-proliferative activities against tested
cancer cell lines. The HTS assay proposed in this study represents a potential
method for discovering more alpha1-AR subtype-selective ligands.
PMID- 25140449
TI - Magnetite nanostructures as novel strategies for anti-infectious therapy.
AB - This review highlights the current situation of antimicrobial resistance and the
use of magnetic nanoparticles (MNPs) in developing novel routes for fighting
infectious diseases. The most important two directions developed recently are:
(i) improved delivery of antimicrobial compounds based on a drastic decrease of
the minimal inhibition concentration (MIC) of the drug used independently; and
(ii) inhibition of microbial attachment and biofilm development on coated medical
surfaces. These new directions represent promising alternatives in the
development of new strategies to eradicate and prevent microbial infections that
involve resistant and biofilm-embedded bacteria. Recent promising applications of
MNPs, as the development of delivery nanocarriers and improved nanovehicles for
the therapy of different diseases are discussed, together with the mechanisms of
microbial inhibition.
PMID- 25140450
TI - Effect of redox modulating NRF2 activators on chronic kidney disease.
AB - Chronic kidney disease (CKD) is featured by a progressive decline of kidney
function and is mainly caused by chronic diseases such as diabetes mellitus and
hypertension. CKD is a complex disease due to cardiovascular complications and
high morbidity; however, there is no single treatment to improve kidney function
in CKD patients. Since biological markers representing oxidative stress are
significantly elevated in CKD patients, oxidative stress is receiving attention
as a contributing factor to CKD pathology. Nuclear factor erythroid-2 related
factor 2 (NRF2) is a predominant transcription factor that regulates the
expression of a wide array of genes encoding antioxidant proteins, thiol
molecules and their generating enzymes, detoxifying enzymes, and stress response
proteins, all of which can counteract inflammatory and oxidative damages. There
is considerable experimental evidence suggesting that NRF2 signaling plays a
protective role in renal injuries that are caused by various pathologic
conditions. In addition, impaired NRF2 activity and consequent target gene
repression have been observed in CKD animals. Therefore, a pharmacological
intervention activating NRF2 signaling can be beneficial in protecting against
kidney dysfunction in CKD. This review article provides an overview of the role
of NRF2 in experimental CKD models and describes current findings on the
renoprotective effects of naturally occurring NRF2 activators, including
sulforaphane, resveratrol, curcumin, and cinnamic aldehyde. These experimental
results, coupled with recent clinical experiences with a synthetic triterpenoid,
bardoxolone methyl, have brought a light of hope for ameliorating CKD progression
by preventing oxidative stress and maintaining cellular redox homeostasis.
PMID- 25140451
TI - Effects of drying methods on physicochemical and immunomodulatory properties of
polysaccharide-protein complexes from litchi pulp.
AB - Dried litchi pulp has been used in traditional remedies in China for many years
to treat various diseases, and the therapeutic activity has been, at least
partly, attributed to the presence of bioactive polysaccharides. Polysaccharide
protein complexes from vacuum freeze-(VF), vacuum microwave-(VM) and heat pump
(HP) dried litchi pulp, which were coded as LP-VF, LP-VM and LP-HP, were
comparatively studied on the physicochemical and immunomodulatory properties. LP
HP had a predominance of galactose, while glucose was the major sugar component
in LP-VF and LP-VM. Compared with LP-VF and LP-VM, LP-HP contained more aspartate
and glutamic in binding protein. LP-HP also exhibited a stronger stimulatory
effect on splenocyte proliferation at 200 MUg/mL and triggered higher NO, TNF
alpha and IL-6 secretion from RAW264.7 macrophages. Different drying methods
caused the difference in physicochemical properties of polysaccharide-protein
complexes from dried litchi pulp, which resulted in significantly different
immunomodulatory activity. HP drying appears to be the best method for preparing
litchi pulp to improve its immunomodulatory properties.
PMID- 25140455
TI - Development and characterization of a resistance spot welding aerosol generator
and inhalation exposure system.
AB - Limited information exists regarding the health risks associated with inhaling
aerosols that are generated during resistance spot welding of metals treated with
adhesives. Toxicology studies evaluating spot welding aerosols are non-existent.
A resistance spot welding aerosol generator and inhalation exposure system was
developed. The system was designed by directing strips of sheet metal that were
treated with an adhesive to two electrodes of a spot welder. Spot welds were made
at a specified distance from each other by a computer-controlled welding gun in a
fume collection chamber. Different target aerosol concentrations were maintained
within the exposure chamber during a 4-h exposure period. In addition, the
exposure system was run in two modes, spark and no spark, which resulted in
different chemical profiles and particle size distributions. Complex aerosols
were produced that contained both metal particulates and volatile organic
compounds (VOCs). Size distribution of the particles was multi-modal. The
majority of particles were chain-like agglomerates of ultrafine primary
particles. The submicron mode of agglomerated particles accounted for the largest
portion of particles in terms of particle number. Metal expulsion during spot
welding caused the formation of larger, more spherical particles (spatter). These
spatter particles appeared in the micron size mode and accounted for the greatest
amount of particles in terms of mass. With this system, it is possible to examine
potential mechanisms by which spot welding aerosols can affect health, as well as
assess which component of the aerosol may be responsible for adverse health
outcomes.
PMID- 25140454
TI - Effects of acute inhalation of aerosols generated during resistance spot welding
with mild-steel on pulmonary, vascular and immune responses in rats.
AB - Spot welding is used in the automotive and aircraft industries, where high-speed,
repetitive welding is needed to join thin sections of metal. Epoxy adhesives are
applied as sealers to the metal seams. Pulmonary function abnormalities and
airway irritation have been reported in spot welders, but no animal toxicology
studies exist. Therefore, the goal of this study was to investigate vascular,
immune and lung toxicity measures after exposure to these metal fumes in an
animal model. Male Sprague-Dawley rats were exposed by inhalation to 25 mg/m3 to
either mild-steel spot welding aerosols with sparking (high metal, HM) or without
sparking (low metal, LM) for 4 h/d for 3, 8 and 13 d. Shams were exposed to
filtered air. Bronchoalveolar lavage (BAL), lung gene expression and ex vivo BAL
cell challenge were performed to assess lung toxicity. Lung resistance (R(L)) was
evaluated before and after challenge with inhaled methacholine (MCh). Functional
assessment of the vascular endothelium in isolated rat tail arteries and
leukocyte differentiation in the spleen and lymph nodes via flow cytometry was
also done. Immediately after exposure, baseline R(L) was significantly elevated
in the LM spot welding aerosols, but returned to control level by 24 h
postexposure. Airway reactivity to MCh was unaffected. Lung inflammation and
cytotoxicity were mild and transient. Lung epithelial permeability was
significantly increased after 3 and 8 d, but not after 13 d of exposure to the HM
aerosol. HM aerosols also caused vascular endothelial dysfunction and increased
CD4+, CD8+ and B cells in the spleen. Only LM aerosols caused increased IL-6 and
MCP-1 levels compared with sham after ex vivo LPS stimulation in BAL macrophages.
Acute inhalation of mild-steel spot welding fumes at occupationally relevant
concentrations may act as an irritant as evidenced by the increased R(L) and
result in endothelial dysfunction, but otherwise had minor effects on the lung.
PMID- 25140456
TI - Sodium/Lithium storage behavior of antimony hollow nanospheres for rechargeable
batteries.
AB - Sodium-ion batteries (SIBs) have come up as an alternative to lithium-ion
batteries (LIBs) for large-scale applications because of abundant Na storage in
the earth's crust. Antimony (Sb) hollow nanospheres (HNSs) obtained by galvanic
replacement were first applied as anode materials for sodium-ion batteries and
exhibited superior electrochemical performances with high reversible capacity of
622.2 mAh g(-1) at a current density of 50 mA g(-1) after 50 cycles, close to the
theoretical capacity (660 mAh g(-1)); even at high current density of 1600 mA g(
1), the reversible capacities can also reach 315 mAh g(-1). The benefits of this
unique structure can also be extended to LIBs, resulting in reversible capacity
of 627.3 mAh g(-1) at a current density of 100 mAh g(-1) after 50 cycles, and at
high current density of 1600 mA g(-1), the reversible capacity is 435.6 mAhg(-1).
Thus, these benefits from the Sb HNSs are able to provide a robust architecture
for SIBs and LIBs anodes.
PMID- 25140457
TI - Antiparasitic efficacy of Gracillin and Zingibernsis newsaponin from Costus
speciosus (Koen ex. Retz) Sm. against Ichthyophthirius multifiliis.
AB - The present study aims to evaluate the antiparasitic activity of active
components from Costus speciosus against Ichthyophthirius multifiliis. Bioassay
guided fractionation was employed to identify active compounds from C. speciosus
yielding 2 bioactive compounds: Gracillin and Zingibernsis newsaponin. In-vitro
assays revealed that Gracillin and Zingibernsis newsaponin could be 100%
effective against I. multifiliis at concentrations of 0.8 and 4.5 mg L(-1), with
median effective concentration (EC50) values of 0.53 and 3.2 mg L(-1),
respectively. All protomonts and encysted tomonts were killed when the
concentrations of Gracillin and Zingibernsis newsaponin were 1.0 and 5.0 mg L(
1). In-vivo experiments demonstrated that fish treated with Gracillin and
Zingibernsis newsaponin at concentrations of 1.0 and 5.0 mg L(-1) carried
significantly fewer parasites than the control (P<0.05). Mortality of fish did
not occur in the treatment group (Zingibernsis newsaponin at 5.0 mg L(-1)) during
the trial, although 100% of untreated fish died. Acute toxicities (LD50) of
Gracillin and Zingibernsis newsaponin for grass carp were 1.64 and 20.7 mg L(-1),
respectively. These results provided evidence that the 2 compounds can be
selected as lead compounds for the development of new drugs against I.
multifiliis.
PMID- 25140459
TI - Synthesis and structures of mononuclear 3,4-bis(trifluoromethyl)pyrrolyl
complexes of Rh(I) and Ni(II).
AB - New mononuclear complexes of the 3,4-bis(trifluoromethyl)pyrrolyl ligand (3,4
(CF3)2-Pyr(-)) with Rh(I) and Ni(II) are reported. Reaction of 3,4-(CF3)2-PyrNa
with [Rh(COD)Cl]2 produces [Rh(PMe3)3(3,4-(CF3)2-Pyr)] (1) while reaction of 3,4
(CF3)2-PyrH with [Ni(PMe3)2Me2] (2) or [Ni(PMe3)2Ph2] (4) gives [trans
Ni(PMe3)2(3,4-(CF3)2-Pyr)(CH3)] (3) or [trans-Ni(PMe3)2(C6H5)(3,4-(CF3)2-Pyr)]
(5) respectively. Complexes 1, 3 and 5 have been characterized spectroscopically
and all five compounds have been structurally characterized by single crystal X
ray diffraction studies.
PMID- 25140460
TI - Horizontal right axillary minithoracotomy: aesthetic and effective option for
atrial and ventricular septal defect repair in infants and toddlers.
AB - INTRODUCTION: Congenital heart defects treatment shows progressive reduction in
morbidity and mortality, however, the scar, resulting from ventricular (VSD) and
atrial septal defect (ASD) repair, may cause discomfort. Right axillary
minithoracotomy approach, by avoiding the breast growth region, is an option for
correction of these defects that may provide better aesthetic results at low
cost. Since October 2011, we have been using this technique for repairing VSD and
ASD defects as well as associated defects. OBJECTIVES: To evaluate the efficacy
of this method in children undergoing correction of VSD and ASD, to compare
perioperative clinical outcomes with those repaired by median sternotomy, and to
evaluate the aesthetic result. METHODS: Perioperative clinical data of 25
patients submitted to axillary thoracotomy were compared with data from a paired
group of 25 patients with similar heart defects repaired by median sternotomy,
from October 2011 to August 2012. RESULTS: Axillary approach was possible even in
infants. There was no mortality and the main perioperative variables were similar
in both groups, except for lower use of blood products in the axillary group
(6/25) vs. control (13/25), with statistical difference (P =0.04). The VSD size
varied from 7 to 15 mm in axillary group. Cannulation of the aorta and vena cavae
was performed through the main incision, whose size ranged from 3 to 5 cm in the
axillary group, with excellent aesthetic results. CONCLUSION: The axillary
thoracotomy was effective, allowing for a heart defect repair similar to the
median sternotomy, with more satisfactory aesthetic results and reduced blood
transfusion, and it can be safely used in infants.
PMID- 25140461
TI - Impact of type of procedure and surgeon on EuroSCORE operative risk validation.
AB - OBJECTIVE: EuroSCORE has been used in cardiac surgery operative risk assessment,
despite important variables were not included. The objective of this study was to
validate EuroSCORE on mortality prediction in a Brazilian cardiovascular surgery
center, defining the influence of type of procedure and surgical team. METHODS:
Between January 2006 and June 2011, 2320 consecutive adult patients were studied.
According to additive EuroSCORE, patients were divided into low risk (score<2),
medium risk (3 - 5), high risk (6 - 11) and very high risk (>12). The relation
between observed mortality (O) and expected mortality (E) according to logistic
EuroSCORE was calculated for each of the groups, types of procedures and surgeons
with > 150 operations, and analyzed by logistic regression. RESULTS: EuroSCORE
correlated to the observed mortality (O/E=0.94; P<0.0001; area under the curve
0.78). However, it overestimated the mortality in very high risk patients
(O/E=0.74; P=0.001). EuroSCORE tended to overestimate isolated myocardial
revascularization mortality (O/E=0.81; P=0.0001) and valve surgery mortality
(O/E=0.89; P=0.007) and it tended to underestimate combined procedures mortality
(O/E=1.09; P<0.0001). EuroSCORE overestimated surgeon A mortality (O/E=0.46;
P<0.0001) and underestimated surgeon B mortality (O/E=1.3; P<0.0001), in every
risk category. CONCLUSION: In the present population, EuroSCORE overestimates
mortality in very high risk patients, being influenced by type of procedure and
surgical team. The most appropriate surgical team may minimize risks imposed by
preoperative profiles.
PMID- 25140462
TI - Predictors of stroke in patients undergoing cardiac surgery.
AB - OBJECTIVE: To determine the risk factors related to the development of stroke in
patients undergoing cardiac surgery. METHODS: A historical cohort study. We
included 4626 patients aged > 18 years who underwent coronary artery bypass
surgery, heart valve replacement surgery alone or heart valve surgery combined
with coronary artery bypass grafting between January 1996 and December 2011. The
relationship between risk predictors and stroke was assessed by logistic
regression model with a significance level of 0.05. RESULTS: The incidence of
stroke was 3% in the overall sample. After logistic regression, the following
risk predictors for stroke were found: age 50-65 years (OR=2.11 - 95% CI 1.05
4.23 - P=0.036) and age >66 years (OR=3.22 - 95% CI 1.6-6.47 - P=0.001), urgent
and emergency surgery (OR=2.03 - 95% CI 1.20-3.45 - P=0.008), aortic valve
disease (OR=2.32 - 95% CI 1.18-4.56 - P=0.014), history of atrial fibrillation
(OR=1.88 - 95% CI 1.05-3.34 - P=0.032), peripheral artery disease (OR=1.81 - 95%
CI 1.13-2.92 - P=0.014), history of cerebrovascular disease (OR=3.42 - 95% CI
2.19-5.35 - P<0.001) and cardiopulmonary bypass time > 110 minutes (OR=1.71 - 95%
CI 1.16-2.53 - P=0.007). Mortality was 31.9% in the stroke group and 8.5% in the
control group (OR=5.06 - 95% CI 3.5-7.33 - P<0.001). CONCLUSION: The study
identified the following risk predictors for stroke after cardiac surgery: age,
urgent and emergency surgery, aortic valve disease, history of atrial
fibrillation, peripheral artery disease, history of cerebrovascular disease and
cardiopulmonary bypass time > 110 minutes.
PMID- 25140464
TI - Comparison of fractal dimension and Shannon entropy in myocytes from rats treated
with histidine-tryptophan-glutamate and histidine-tryptophan cetoglutarate.
AB - INTRODUCTION: Solutions that cause elective cardiac arrest are constantly
evolving, but the ideal compound has not yet been found. The authors compare a
new cardioplegic solution with histidine-tryptophan-glutamate (Group 2) and other
one with histidine-tryptophan-cetoglutarate (Group 1) in a model of isolated rat
heart. OBJECTIVE: To quantify the fractal dimension and Shannon entropy in rat
myocytes subjected to cardioplegia solution using histidine-tryptophan with
glutamate in an experimental model, considering the caspase markers, IL-8 and KI
67. METHODS: Twenty male Wistar rats were anesthetized and heparinized. The chest
was opened, the heart was withdrawn and 40 ml/kg of cardioplegia (with histidine
tryptophan-cetoglutarate or histidine-tryptophan-glutamate solution) was infused.
The hearts were kept for 2 hours at 4oC in the same solution, and thereafter
placed in the Langendorff apparatus for 30 min with Ringer-Locke solution.
Analyzes were performed for immunohistochemical caspase, IL-8 and KI-67. RESULTS:
The fractal dimension and Shannon entropy were not different between groups
histidine-tryptophan-glutamate and histidine-tryptophan-acetoglutarate.
CONCLUSION: The amount of information measured by Shannon entropy and the
distribution thereof (given by fractal dimension) of the slices treated with
histidine-tryptophan-cetoglutarate and histidine-tryptophan-glutamate were not
different, showing that the histidine-tryptophan-glutamate solution is as good as
histidine-tryptophan-acetoglutarate to preserve myocytes in isolated rat heart.
PMID- 25140465
TI - Pain and cardiorespiratory responses of children during physiotherapy after heart
surgery.
AB - OBJECTIVE: The aim of the present study was to determine the occurrence of pain
and changes in blood pressure, heart rate, respiratory rate, and arterial oxygen
saturation associated with physiotherapy in children undergoing cardiac surgery.
METHODS: Eighteen extubated children were assessed for the presence of pain using
the face, legs, activity, cry, consolability scale, and blood pressure, heart
rate, respiratory rate and arterial oxygen saturation were simultaneously
recorded. The physiological parameters were measured at the following time
periods: immediately before physiotherapy, five and 10 minutes after the
beginning of physiotherapy, and five minutes after its end. Pain was assessed
immediately before physiotherapy, ten minutes after the beginning of
physiotherapy and five minutes after its end. Pain and physiological changes were
assessed by the Friedman test and the correlation between the physiological
parameters and the pain scores was assessed by the Spearman test. RESULTS: Pain
increased during physiotherapy and decreased significantly after it compared to
pre-physiotherapy scores. Systolic blood pressure and heart rate increased
significantly after 10 minutes of the beginning of physiotherapy. Arterial oxygen
saturation tended to decrease during physiotherapy and to increase after it,
although without significance. The correlation between pain scores and the
physiological variables was significant only for systolic blood pressure and
heart rate ten minutes after the beginning of physiotherapy. CONCLUSION:
Manipulation after the beginning of physiotherapy seems to be accompanied by
significant pain and by important associated cardiovascular changes. Apparent
analgesia and improved respiratory function were observed after respiratory
physiotherapy.
PMID- 25140463
TI - Analysis of transit time flow of the right internal thoracic artery anastomosed
to the left anterior descending artery compared to the left internal thoracic
artery.
AB - INTRODUCTION: We evaluated with transit time flow the performance of the right
and left thoracic arteries when used as a graft for the left anterior descending
artery. METHODS: Fifty patients undergoing surgery for myocardial
revascularization without cardiopulmonary bypass were divided into two groups. In
group A patients received graft of right internal mammary artery to the anterior
interventricular branch. In group B patients received graft of left internal
mammary artery to the same branch. At the end of the operation the flow was
assessed by measuring transit time. RESULTS: In group A, mean age was 60.6 +/-
9.49 years. The average height and weight of the group was 80.4 +/- 10.32 kg and
169.2 +/- 6.86 cm. The average number of grafts per patient in this group was
3.28 +/- 1.49. The mean flow and distal resistance obtained in right internal
thoracic artery was 42.1 +/- 23.4 ml/min and 2.8 +/- 0.9 respectively. In group
B, the mean age was 59.8 +/- 9.7 years. The average height and weight of this
group was 77.7 +/- 14.22 kg and 166.0 +/- 8.2 cm. The average number of grafts
per patient in this group was 3.08 +/- 0.82. The mean flow and distal resistance
observed in this group was 34.2 +/- 19.1 ml/min and 2.0 +/- 0.7. There were no
deaths in this series. CONCLUSION: Right internal mammary artery presented a
similar behavior to left internal mammary artery when anastomosed to the anterior
interventricular branch of the left coronary artery. There was no statistical
difference between the measured flow obtained between both arteries.
PMID- 25140466
TI - Impact of hospital infections on patients outcomes undergoing cardiac surgery at
Santa Casa de Misericordia de Marilia.
AB - OBJECTIVE: This study aimed to determine the incidence of nosocomial infections,
the risk factors and the impact of these infections on mortality among patients
undergoing to cardiac surgery. METHODS: Retrospective cohort study of 2060
consecutive patients from 2006 to 2012 at the Santa Casa de Misericordia de
Marilia. RESULTS: 351 nosocomial infections were diagnosed (17%), 227 non
surgical infections and 124 surgical wound infections. Major infections were
mediastinitis (2.0%), urinary tract infection (2.8%), pneumonia (2.3%), and
bloodstream infection (1.7%). The in-hospital mortality was 6.4%. Independent
variables associated with non-surgical infections were age > 60 years (OR 1.59,
95% CI 1.09 to 2.31), ICU stay > 2 days (OR 5, 49, 95% CI 2.98 to 10, 09),
mechanical ventilation > 2 days (OR11, 93, 95% CI 6.1 to 23.08), use of urinary
catheter > 3 days (OR 4.85 95% CI 2.95 -7.99). Non-surgical nosocomial infections
were more frequent in patients with surgical wound infection (32.3% versus 7.2%,
OR 6.1, 95% CI 4.03 to 9.24). Independent variables associated with mortality
were age greater than 60 years (OR 2.0; 95% CI 1.4 t o3.0), use of vasoactive
drugs (OR 3.4, 95% CI 1.9 to 6, 0), insulin use (OR 1.8; 95% CI 1.2 to 2.8),
surgical reintervention (OR 4.4; 95% CI 2.1 to 9.0) pneumonia (OR 4.3; 95% CI 2.1
to 8.9) and bloodstream infection (OR = 4.7, 95% CI 2.0 to 11.2). CONCLUSION: Non
surgical hospital infections are common in patients undergoing cardiac surgery;
they increase the chance of surgical wound infection and mortality.
PMID- 25140468
TI - High postoperative serum levels of surfactant type B as novel prognostic markers
for congenital heart surgery.
AB - OBJECTIVE: Congenital heart diseases are observed in 5 to 8 of every 1000 live
births. The presence of a valuable biomarker during the surgical periods may aid
the clinician in a more accurate prognosis during treatment. METHODS: For this
reason, surfactant protein B plasma levels may help to evaluate patients with
cardiac problems diminishing the alveolocapillary membrane stability. In this
study, plasma levels of this biomarker were measured in the preoperative and
postoperative periods. This study was conducted to detect the differences between
pulmonary hypertensive and normotensive patients. The differences before and
after cardiopulmonary bypass were examined. RESULTS: The differences in
cardiopulmonary bypass time, cross-clamp time , inotropic support dose, and
duration of intensive care of patients with and without pulmonary hypertensive
were found to be statistically significant (P<0.05). The results revealed that
this pathophysiological state was related to other variables that were studied.
We believe that the differences in preoperative and postoperative SPB levels
could be attributed to alveolocapillary membrane damage and alveolar surfactant
dysfunction. We found that this pathophysiological condition was significantly
associated with postoperative parameters. CONCLUSION: The findings of the current
study showed that surfactant protein B was present in the blood of patients with
a congenital heart disease during the preoperative period. Long by-pass times may
exert damage to the alveolocapillary membrane in patients with pulmonary
hypertension and preoperative heart failure, and it is recommended to keep the
option of surfactant therapy in mind during the postoperative course at the
intensive care unit before preparing the patients for extubation.
PMID- 25140467
TI - Management of multivessel coronary disease after primary angioplasty: staged
reintervention versus optimized clinical treatment and two-year follow-up.
AB - OBJECTIVE: In the clinical scenario of ST-segment elevation acute myocardial
infarction, several patients with multivessel coronary atherosclerotic disease
are discharged without a defined strategy to monitor the residual atherosclerotic
lesions. The clinical endpoints evaluated were cardiovascular death, symptoms of
angina pectoris, rehospitalization for a new acute coronary syndrome, and the
necessity of reintervention during the two-year follow-up. METHODS: This
observational, prospective, and historical study included multivessel coronary
atherosclerotic disease patients who were admitted to a tertiary care university
hospital with ST-segment elevation acute myocardial infarction and underwent
primary percutaneous coronary intervention with stent implantation only at the
culprit lesion site; these patients were monitored in the outpatient clinic
according to two treatments: the Clinical Group - CG (optimized pharmacological
therapy associated with counseling for a healthy diet and cardiac rehabilitation)
or the Intervention Group - IG (new staged percutaneous coronary intervention or
surgical coronary artery bypass graft surgery combined with the previously
prescribed treatment). RESULTS: Of 143 patients consecutively admitted with ST
segment elevation acute myocardial infarction, 57 were eligible for the study
(CG=44 and IG=13). Regarding the clinical endpoints, the cardiovascular death
rate did not differ between the CG and IG. The symptom of angina pectoris and the
rehospitalization rate for a new episode of acute coronary syndrome were
accentuated in the CG (P=0.020 and P=0.049, respectively) mainly in individuals
with evidence of ischemia evidenced by myocardial scintigraphy (P<0.001 and
P=0.001, respectively) which culminated in an even greater need for
reintervention (P=0.001) in this subgroup of patients. CONCLUSION: The staged
intervention was demonstrated to be safe and able to reduce angina pectoris and
rehospitalization for a new episode of acute coronary syndrome. In addition, it
decreases the likelihood of unplanned reinterventions of patients without
ischemia evidenced by myocardial scintigraphy.
PMID- 25140469
TI - Comparative analysis of the patency of the internal thoracic artery in the CABG
of left anterior descending artery: 6-month postoperative coronary CT angiography
evaluation.
AB - OBJECTIVE: To assess the patency of the pedicled right internal thoracic artery
with an anteroaortic course and compare it to the patency of the left internal
thoracic artery , in anastomosis to the left anterior descending artery in
coronary artery bypass grafting by using coronary CT angiography at 6 months
postoperatively. METHODS: Between December 2008 and December 2011, 100 patients
were selected to undergo a prospective coronary artery bypass grafting procedure
without cardiopulmonary bypass. The patients were randomly divided by a computer
generated list into Group-1 (G-1) and Group-2 (G-2), comprising 50 patients each,
the technique used was known at the beginning of the surgery. In G-1, coronary
artery bypass grafting was performed using the left internal thoracic artery for
the left anterior descending and the free right internal thoracic artery for the
circumflex, and in G-2, coronary artery bypass grafting was performed using the
right internal thoracic artery pedicled to the left anterior descending and the
left internal thoracic artery pedicled to the circumflex territory. RESULTS: The
groups were similar with regard to the preoperative clinical data. A male
predominance of 75.6% and 88% was observed in G-1 and G-2, respectively. Five
patients migrated from G-1 to G-2 because of atheromatous disease in the
ascending aorta. The average number of distal anastomoses was 3.48 (SD=0.72) in G
1 and 3.20 (SD=0.76) in G-2. Coronary CT angiography in 96 re-evaluated patients
showed that all ITAs, right or left, used in situ for the left anterior
descending were patent. There were no deaths in either group. CONCLUSION:
Coronary artery bypass grafting surgery involving anastomosis of the anteroaortic
right internal thoracic artery to the left anterior descending artery has an
outcome similar to that obtained using the left internal thoracic artery for the
same coronary site.
PMID- 25140471
TI - Morphologic expression of the left coronary artery in pigs. An approach in
relation to human heart.
AB - INTRODUCTION: In spite of its importance as an experimental model, the
information on the left coronary artery in pigs is sparse. OBJECTIVE: To
determine the morphologic features of the left coronary artery in pigs. METHODS:
We evaluated 158 pig hearts. The left coronary artery was perfused with synthetic
resin after their ostia had been catheterized. Diameters and courses of the
vascular beds were measured with an electronic caliper (Mitutoyo(r)). RESULTS:
The diameter of left coronary artery was 6.98 +/- 1.56 mm and its length was 3.51
+/- 0.99 mm. It was found to end up by bifurcating itself into the anterior
interventricular artery and the circumflex artery in 79% of the cases, and by
trifurcating in 21% of the cases, with the presence of the diagonal artery. The
anterior interventricular artery ended up at the apex in 79.7% of the cases, and
the circumflex artery at the posterior aspect of the left ventricle in 64% of the
case, this artery never reached the posterior interventricular sulcus. An
anastomosis between the terminal branches of the anterior interventricular artery
and the posterior interventricular artery was found in 7.6% of the specimens. The
antero-superior branch of the anterior interventricular artery occurred in 89.9%
of the hearts. A left marginal branch was observed in 87.9% of the cases with a
diameter of 2.25 +/- 0.55 mm. CONCLUSION: Compared with humans, pigs have shorter
left coronary artery trunks and branches; even the circumflex artery never
reaches the posterior interventricular sulcus. Our findings are useful for the
design of experimental hemodynamic and procedural models.
PMID- 25140470
TI - Myocardial regeneration after implantation of porcine small intestinal submucosa
in the left ventricle.
AB - INTRODUCTION: Most cardiomyocytes do not regenerate after myocardial infarction.
Porcine small intestinal submucosa has been shown to be effective in tissue
repair. OBJECTIVE: To evaluate myocardial tissue regeneration and functional
effects of SIS implantation in pigs after left ventriculotomy. METHODS: Fifteen
pigs were assigned to two groups: porcine small intestinal submucosa (SIS) (N=10)
and control (N=5). The SIS group underwent a mini sternotomy, left ventriculotomy
and placement of a SIS patch. The control group underwent a sham procedure.
Echocardiography was performed before and 60 days after the surgical procedure.
Histological analysis was performed with hematoxylin-eosin stain and markers for
actin 1A4, anti sarcomeric actin, connexin43 and factor VIII. RESULTS: Weight
gain was similar in both groups. Echocardiography analysis revealed no difference
between groups regarding end diastolic and systolic diameters and left
ventricular ejection fraction, both pre (P=0.118, P=0.313, P=0.944) and post
procedure (P=0.333, P=0.522, P=0.628). Both groups showed an increase in end
diastolic (P<0,001 for both) and systolic diameter 60 days after surgery
(P=0.005, SIS group and P=0.004, control group). New cardiomyocytes, blood
vessels and inflammatory reactions were histologically identified in the SIS
group. CONCLUSION: SIS implantation in pigs after left ventriculotomy was
associated with angiomuscular regeneration and no damage in cardiac function.
PMID- 25140472
TI - Preoperative therapy restores ventilatory parameters and reduces length of stay
in patients undergoing myocardial revascularization.
AB - INTRODUCTION: The frequency of surgical procedures has increased steadily in
recent decades, including the myocardial revascularization. OBJECTIVES: To
demonstrate the importance of physiotherapy in the preoperative period of cardiac
surgery in relation to the reduction of hospital stay, changes in lung volumes
and respiratory muscle strength. METHODS: We conducted a prospective study with
patients undergoing myocardial revascularization, the Hospital das Clinicas da
Universidade Estadual Paulista (UNESP)/Botucatu - SP. We evaluated 70 patients of
both genders, aged between 40 and 75 years, subdivided into two groups: group I -
35 patients of both genders, who received a written protocol guidance, breathing
exercises and respiratory muscle training in the preoperative period and group II
- 35 patients of both genders, who received only orientation of the ward on the
day of surgery. This study was approved by the Ethics Committee of UNESP /
Botucatu - SP. RESULTS: Maximal inspiratory pressure in third postoperative day
and fifth postoperative day and significant difference between groups, being
better for the intervention group. Expiratory pressure was significant in fifth
postoperative day in the intervention group compared to controls. The difference
of length of hospital stay in the postoperative was found between the groups with
shorter hospital stay in the group receiving preoperative therapy. CONCLUSION:
Physical therapy plays an important role in the preoperative period, so that
individuals in the intervention group more readily restored the parameters
evaluated before surgery, in addition, there was a decrease in the time of the
postoperative hospital stay. Thus, it is thought the cost-effectiveness of a
program of preoperative physiotherapy.
PMID- 25140474
TI - Left subclavian artery stenting: an option for the treatment of the coronary
subclavian steal syndrome.
AB - INTRODUCTION: The subclavian steal syndrome is characterized by the vertebral
artery flow inversion, due to a stenotic lesion in the origin of the subclavian
artery. The Coronary-subclavian Steal Syndrome is a variation of the Subclavian
Steal Syndrome and is characterized by inversion of flow in the Internal Thracic
artery that has been used as conduct in a myocardial revascularization. Its
diagnosis must be suspected in patients with difference in pulse and arterial
pressure in the upper limbs, that present with angina pectoris and that have done
a myocardial revascularization. Its treatment must be a surgical bypass or a
transluminal angioplasty. OBJECTIVE: The objective is to show the left subclavian
artery stenting as a safe and effective method to treat the coronary-subclavian
steal syndrome. METHODS: Historical prospective, non-randomized trial, through
revision of the hospital records of the patients treated with the stenting of the
left subclavian artery, from January 2006 to September 2012. RESULTS: In the
mentioned period, 4.291 miocardial revascularizations were performed with the use
of the left mammary artery, and 16 patients were identified to have the Coronary
subclavian steal syndrome. All of them were submitted to endovascular treatment.
The success rate was 100%; two patients experienced minor complications; none of
them presented with major complications. Eleven of the 16 patients had
ultrassonographic documentation of patent stent for at least one year; two
patients lost follow up and other two died. CONCLUSION: The stenting of the left
subclavian artery is a good option for the treatment of the Coronary-subclavian
Steal Syndrome, with high level of technical and clinical success.
PMID- 25140473
TI - Improvement in cardioplegic perfusion technique in single aortic clamping -
initial results.
AB - INTRODUCTION: The most common method used for myocardial protection is
administering cardioplegic solution in the coronary circulation. Nevertheless,
protection may be achieved by intermittent perfusion of the coronary system with
patient's own blood. The intermittent perfusion may be performed by multiple
sequences of clamping and opening of the aortic clamp or due single clamping and
accessory cannulation of the aortic root as in the improved technique proposed in
this study, reperfusion without the need for multiple clamping of the aorta.
OBJECTIVE: To evaluate the clinical outcome and the occurrence of neurological
events in in-hospital patients submitted to myocardial revascularization surgery
with the "improved technique" of intermittent perfusion of the aortic root with
single clamping. METHODS: This is a prospective, cross-sectional, observational
study that describes a myocardial management technique that consists of
intermittent perfusion of the aortic root with single clamping in which 50
patients (mean age 58.5 +/- 7.19 years old) have been submitted to the myocardial
revasculrization surgery under the proposed technique. Clinical and laboratory
variables, pre- and post-surgery, have been assessed. RESULTS: The mean peak
level of post-surgery CKMB was 51.64 +/- 27.10 U/L in the second post-surgery and
of troponin I was 3.35 +/- 4.39 ng/ml in the fourth post-surgery, within normal
limits. No deaths have occurred and one patient presented mild neurological
disorder. Hemodynamic monitoring has not indicated any changes. CONCLUSION: The
myocardial revascularization surgery by perfusion with the improved technique
with intermittent aortic root with single clamping proved to be safe, enabling
satisfactory clinical results.
PMID- 25140475
TI - Evolution of weight and height of children with congenital heart disease
undergoing surgical treatment.
AB - OBJECTIVE: To evaluate the height and weight development of children with
congenital heart disease undergoing surgery with the goal of determining when
they reach the threshold of normal development and whether there are differences
between patients with developmental pattern below the level of normality
preoperatively (z-score<-2 for the analyzed parameter) in comparison to the total
group of cardiac patients. METHODS: We prospectively followed up 27 children
undergoing operation into five time periods: preoperatively and at four
subsequent outpatient appointments: 1st month, 3rd month, 6th month and 12th
month after hospital discharge. The anthropometric parameters used were median z
score (MZ), weight (WAZ), height (HAZ), subscapular skinfold (SSFAZ), upper arm
circumference (UAC) and triceps skinfold (TSFAZ). The evolution assessment of the
parameters was performed by analysis of variance and comparison with the general
normal population from unpaired t test, both in the total group of cardiac
patients, and in subgroups with preoperative parameters below the normal level
(Zm<-2). RESULTS: In the total group there was no significant evolution of MZ of
all parameters. WAZ was statistically lower than the normal population until the
1st month of follow-up (P=0.028); HAZ only preoperatively (P=0.044), SSFAZ in the
first month (P=0.015) and at 12th month (P=0.038), UAC and TSFAZ were always
statistically equal to the general population. In patients whose development was
below the level of normality, there were important variation of WAZ (P=0.002),
HAZ (P=0.001) and UAC (P=0.031) after the operation, and the WAZ was lower than
the normal population until the 3rd month (P=0.015); HAZ and UAC, until the first
month (P=0.024 and P=0.039 respectively), SSFAZ, up to the 12th month (P=0.005),
the TSFAZ only preoperatively (P=0.011). CONCLUSION: The operation promoted the
return to normalcy for those with heart disease in general within up to three
months, but for the group of patients below normal developmental pattern of the
return occurred within 12 months.
PMID- 25140476
TI - The calcium paradox - what should we have to fear?
AB - The calcium paradox was first mentioned in 1966 by Zimmerman et al. Thereafter
gained great interest from the scientific community due to the fact of the
absence of calcium ions in heart muscle cells produce damage similar to ischemia
reperfusion. Although not all known mechanisms involved in cellular injury in the
calcium paradox intercellular connection maintained only by nexus seems to have a
key role in cellular fragmentation. The addition of small concentrations of
calcium, calcium channel blockers, and hyponatraemia hypothermia are important to
prevent any cellular damage during reperfusion solutions with physiological
concentration of calcium.
PMID- 25140477
TI - Cardiac risk stratification in cardiac rehabilitation programs: a review of
protocols.
AB - OBJECTIVE: Gather and describe general characteristics of different protocols of
risk stratification for cardiac patients undergoing exercise. METHODS: We
conducted searches in LILACS, IBECS, MEDLINE, Cochrane Library, and SciELO
electronic databases, using the following descriptors: Cardiovascular Disease,
Rehabilitation Centers, Practice Guideline, Exercise and Risk Stratification in
the past 20 years. RESULTS: Were selected eight studies addressing methods of
risk stratification in patients undergoing exercise. CONCLUSION: None of the
methods described could cover every situation the patient can be subjected to;
however, they are essential to exercise prescription.
PMID- 25140478
TI - Vacuum-assisted drainage in cardiopulmonary bypass: advantages and disadvantages.
AB - Systematic review of vacuum assisted drainage in cardiopulmonary bypass,
demonstrating its advantages and disadvantages, by case reports and evidence
about its effects on microcirculation. We conducted a systematic search on the
period 1997-2012, in the databases PubMed, Medline, Lilacs and SciELO. Of the 70
selected articles, 26 were included in the review. Although the vacuum assisted
drainage has significant potential for complications and requires appropriate
technology and professionalism, prevailed in literature reviewed the concept that
vacuum assisted drainage contributed in reducing the rate of transfusions,
hemodilutions, better operative field, no significant increase in hemolysis,
reduced complications surgical, use of lower prime and of smaller diameter
cannulas.
PMID- 25140479
TI - Biocompatibility of Ricinus communis polymer with addition of calcium carbonate
compared to titanium. Experimental study in guinea pigs.
AB - OBJECTIVE: The aim of the present investigation was to determine whether the
difference in inflammatory tissue reaction between the Riccinus communis (castor)
polymer with calcium carbonate and the titanium implant is statistically
significant. METHODS: Thirty-two Cavia porcellus were allocated into four groups
of eight animals each. We implanted the two types of materials in the
retroperitoneal space of all the animals. They were euthanized at 7, 20, 30 and
40 days after surgery, and an histological study of the samples was conducted.
RESULTS: All implants showed characteristics of chronic inflammation regardless
of the material and timepoint of evaluation. There was no statistically
significant difference between Pm+CaCO3 and Ti with regard to the presence of
granulation tissue, tissue congestion, histiocytes, lymphocytes, neutrophils,
giant cells, and fibrosis (P> 0.05). CONCLUSION: The castor oil polymer plus
calcium carbonate implant was not statistically different from the titanium
implant regarding inflammatory tissue reaction.
PMID- 25140480
TI - The use of virtual resources in preoperative preparation of infrarenal aneurysms:
exploring the OsiriX's potential.
AB - INTRODUCTION: In the past few years, the increase of endovascular surgeons'
interest on tomography image edition through softwares is marked specially when
it concerns to its use on preoperatory study for endovascular aneurysm repair. It
is presumed that the bigger the number of informations extracted from the
tomography exam and its three-dimensional reconstruction, the smaller is the need
of patient's exposure to contrast, as well as the its exposure and the surgical
team to radiation. Concepts of image manipulation on the OsiriX software with
volume reconstruction of tridimensional tomographic scans of virtual fluoroscopy
were used. METHODS: Through manipulation of multi-slice tomography images under
three-dimensional reconstruction on software, it was able to modify values of the
exam's dose-irradiated distribution. These volume reconstruction presets were
saved as Virtual Fluoroscopy, reproducible upon any OsiriX platform. It was able
to construct a biplanar image appearing to the patient's operatory fluoroscopy.
When compared to the intraoperatory angiography, the images were alike.
DISCUSSION: Dose-irradiated distribution data manipulation allowed to visualize
as opaque bone surfaces and transparent low-dose radiation's areas (viscerae).
Thus, under previously marked renal arteries, it was possible to predict it's
anatomical positioning related to visualization under real fluoroscopy.
Foretelling the better positioning of the C-arm through this technique enables to
obtain images with the minimum influence of parallax effect. It is believed that
it supports to assess the renal arteries topographic positioning on a bi
dimensional intraoperatory image. The need of frequent angiographies to localize
the renal arteries is reduced, decreasing the exposure to contrast on vulnerable
patients.
PMID- 25140481
TI - Intracardiac embolization of inferior vena cava filter associated with right
atrium perforation and cardiac tamponade.
AB - Insertion of inferior vena cava filters has been well established in literature,
reducing occurrence of pulmonary embolism after an episode of deep venous
thrombosis in patients with contraindication to anticoagulation. There are a
small number of complications related to procedure and embolization is rare. In
this context, we described a case of intracardiac embolization associated with
cardiac tamponade.
PMID- 25140482
TI - Comment on "depression after CABG: a prospective study.".
PMID- 25140484
TI - Condemnation to plagiarism.
PMID- 25140485
TI - Brazilian Registry of Cardiovascular Surgery in Adults. From design to reality.
PMID- 25140486
TI - Increasing isolated right heart chambers in second trimester ultrasound: always a
warning sign?
PMID- 25140487
TI - Associations between birth weight, preeclampsia and cognitive functions in middle
aged adults.
AB - Both reductions in birth weight and preeclampsia (PE) have been associated with
decrements in scores on tests of intelligence in children and adolescents. We
examined whether these decrements persist into middle adulthood and expand into
other domains of cognitive functioning. Using data from the Early Determinants of
Adult Health project and from the ancillary project, Fetal Antecedents of Major
Depression and Cardiovascular Disease, we selected term same-sex sibling sets or
singletons from these sets, from the New England Family Study (NEFS) and the
Child Health and Development Studies (CHDS), discordant on either fetal growth or
PE, to test the hypotheses that prenatal exposure to inflammation was associated
with decrements in attention, learning and executive function 40 years later.
Exposure was defined as a continuous measure of percentile birth weight for
gestational age, reduced fetal growth (<20th percentile of birth weight for
gestational age) or maternal PE. Given that the sample was comprised, in part, of
sibling sets, the analyses were performed using mixed models to account for the
inter-sibling correlations. Analyses were performed separately by study site
(i.e. NEFS and CHDS). We found few statistically significant associations
(suggesting a possible type II error) consistent with previous literature,
suggesting that the associations with low birth weight do not persist into
midlife. We discuss the possible reasons for the lack of associations, which
include the possible mediating effects of the postnatal environment.
PMID- 25140489
TI - The energy release rate of a pressurized crack in soft elastic materials: effects
of surface tension and large deformation.
AB - In this paper we present a theoretical study on how surface tension affects
fracture of soft solids. In classical fracture theory, the resistance to fracture
is partly attributed to the energy required to create new surfaces. Thus, the
energy released to the crack tip must overcome the surface energy in order to
propagate a crack. In soft materials, however, surface tension can cause
significant deformation and can reduce the energy release rate for crack
propagation by resisting the stretch of crack surfaces. We quantify this effect
by studying the inflation of a penny-shaped crack in an infinite elastic body
with applied pressure. To avoid numerical difficulty caused by singular fields
near the crack tip, we derived an expression for the energy release rate which
depends on the applied pressure, the surface tension, the inflated crack volume
and the deformed crack area. This expression is evaluated using a newly developed
finite element method with surface tension elements. Our calculation shows that,
when the elasto-capillary number omega = sigma/Ea is sufficiently large, where
sigma is the isotropic surface tension, E is the small strain Young's modulus and
a is the initial crack radius, both the energy release rate and the crack opening
displacement of an incompressible neo-Hookean solid are significantly reduced by
surface tension. For a sufficiently high elasto-capillary number, the energy
release rate can be negative for applied pressure less than a critical amount,
suggesting that surface tension can cause crack healing in soft elastic
materials.
PMID- 25140488
TI - Effect of maternal coffee, smoking and drinking behavior on adult son's semen
quality: prospective evidence from the Child Health and Development Studies.
AB - Fetal exposure to caffeine is associated with adverse pregnancy outcomes. Animal
and human studies suggest that caffeine may have effects on the developing
reproductive system. Here we report on mothers' smoking, coffee and alcohol use,
recorded during pregnancy, and semen quality in sons in the age group of 38-47
years. Subjects were a subset of the Child Health and Development Studies, a
pregnancy cohort enrolled between 1959 and 1967 in the Kaiser Foundation Health
Plan near Oakland, California. In 2005, adult sons participated in a follow-up
study (n = 338) and semen samples were donated by 196 participants. Samples were
analyzed for sperm concentration, motility and morphology according to the
National Cooperative Reproductive Medicine Network (Fertile Male Study) Protocol.
Mean sperm concentration was reduced by approximately 16 million sperms for sons
with high prenatal exposure (5 cups of maternal coffee use per day) compared with
unexposed sons (P-value for decreasing trend = 0.09), which translates to a
proportionate reduction of 25%. Mean percent motile sperm decreased by
approximately 7 points (P-value = 0.04), a proportionate decline of 13%, and mean
percent sperm with normal morphology decreased by approximately 2 points (P-value
= 0.01), a proportionate decline of 25%. Maternal cigarette and alcohol use were
not associated with son's semen quality. Adjusting for son's contemporary coffee,
alcohol and cigarette use did not explain the maternal associations. Findings for
son's coffee intake and father's prenatal coffee, cigarette and alcohol use were
non-significant and inconclusive. These results contribute to the evidence that
maternal coffee use during pregnancy may impair the reproductive development of
the male fetus.
PMID- 25140490
TI - To assemble or fold?
AB - This communication reports an elegant structure formation by an amide
functionalized donor (D)-acceptor (A) dyad by stepwise folding and assembly. It
adopts a folded conformation by intra-chain CT-interaction that subsequently
dimerizes by inter-molecular H-bonding to produce a folded dimer (FD) with a DAAD
stacking sequence. Incompatibility of the aromatic stacked face with MCH triggers
macroscopic assembly by solvophobically driven edge-to-edge stacking of the FD
with concomitant growth in the orthogonal direction by D-D pi-stacking leading to
the formation of a reverse-vesicle.
PMID- 25140493
TI - Prenatal diagnosis of Loeys-Dietz syndrome.
PMID- 25140492
TI - Gas-phase synthesis and reactivity of Cu(+)-benzyne complexes.
AB - Cu(+)-benzyne complexes bearing bidentate nitrogen ligands were synthesized in
the gas phase for the first time using electrospray ionization mass spectrometry.
The addition reactivity of copper-stabilized benzyne with amines was studied in
the ion trap analyzer. The structures of products were identified by comparing
their MS(n) data with authentic compounds obtained from another generation route.
PMID- 25140494
TI - First experience with three-dimensional speckle tracking (3D wall motion
tracking) in fetal echocardiography.
AB - OBJECTIVES: Fetal cardiac function can be quantified by different methods. This
is the first approach of real three-dimensional(3 D)-based speckle tracking
echocardiography in the fetus to assess different cardiac strain parameters.
METHODS: We present preliminary results of fetal global myocardial strain
analyses. For fetal echocardiography a Toshiba Artida system was used. Based on
an apical or basal four-chamber view of the fetal heart, raw data volumes with a
high temporal resolution were acquired and digitally stored. RESULTS: 8
individual healthy fetuses with an echocardiogram performed between 21 and 37
weeks of gestation were included. The mean temporal resolution was 31.2 +/- 4.3
volumes per second (vps). Basic parameters such as longitudinal and
circumferential strain as well as advanced 3 D myocardial motion patterns such as
area strain, rotation, twist and torsion were assessed. CONCLUSION: Currently the
assessment of fetal myocardial deformation parameters by 3 D speckle tracking
seems to be technically feasible only in individual cases. In the future further
development of this technique is necessary to improve its application in fetal
echocardiography.
PMID- 25140495
TI - A Comparison of the Diagnostic Accuracy and Reliability of Subjective Grading and
Computer-Aided Assessment of Intranodal Vascularity in Differentiating Metastatic
and Reactive Cervical Lymphadenopathy.
AB - PURPOSE: Ultrasound is a well-established imaging modality in the assessment of
malignant cervical lymphadenopathy. With the use of Doppler ultrasound,
intranodal vascularity can be evaluated. However, the major limitation of
ultrasound is operator dependency. Therefore, this study aimed to evaluate and
compare the diagnostic accuracy and reliability of the subjective grading and
computer-aided approach in assessing intranodal vascularity for the
differentiation of benign and malignant lymph nodes. MATERIALS AND METHODS: The
present study retrospectively assessed 99 power Doppler ultrasound images of
cervical lymph nodes and evaluated the degree of intranodal vascularity using
qualitative subjective grading (QSG) and quantitative computer-aided (QCA)
methods. The diagnostic accuracy of the two methods in distinguishing metastatic
and reactive nodes and their inter- and intra-rater reliability in assessing
intranodal vascularity were evaluated and compared. RESULTS: The results showed
that the QCA method was more accurate than the QSG method with a significantly
higher sensitivity (67.8 % and 61.9 %, respectively, p < 0.05) and specificity
(73.3 % and 57.3 %, respectively, p < 0.05). Using the intranodal vascularity
index as determined by the QCA approach, the optimum cut-off to differentiate
metastatic and reactive cervical lymph nodes was 32 %. The QCA method showed
higher inter- and intra-rater reliability than the QSG method. CONCLUSION: In the
assessment of the degree of intranodal vascularity, the QCA method was more
accurate and reliable than the QSG method in distinguishing metastatic and
reactive lymph nodes.
PMID- 25140496
TI - Contrast-enhanced ultrasound and real-time elastography for the diagnosis of
benign Leydig cell tumors of the testis - a single center report on 13 cases.
AB - PURPOSE: To describe sonomorphological features in testicular Leydig cell tumors
(LCTs) with a special focus on contrast-enhanced ultrasonography (CEUS) and real
time elastography (RTE). PATIENTS AND METHODS: In a series of 186 patients with
testicular surgery for neoplastic disease, 13 benign LCTs (in 12 patients) were
histopathologically diagnosed. Preoperatively, all patients had been examined
with a standardized protocol (high-resolution grayscale and color-coded
ultrasonography, CEUS). 5 patients underwent RTE. In CEUS, the filling time of
the lesion was compared to that of 14 size-matched germ cell tumors (GCT).
RESULTS: 10/13 LCTs had a size of < 10 mm, and a sharply demarcated hypoechoic
appearance was typical (10/13). Color-coded ultrasonography detected signals in 8
lesions, while CEUS showed clear hypervascularization in all. LCTs had a
significantly shorter filling time than GCTs (p < 0.0005), with 9/13 LCTs being
completely filled within 4 s. In RTE, all 5 examined lesions were clearly
"harder" than the surrounding testicular tissue. CONCLUSION: Contrary to some
earlier reports, we could demonstrate marked hypervascularization in LCTs. This
feature clearly allows for the differentiation of a small LCT from focal scars.
However, it may only be visible on CEUS. In CEUS, LCT is suggested by the
findings of a short filling time or by a circumferential vessel with a rapid
centripetal filling, combined with a "harder" appearance in RTE. These features
along with the findings of a small and peripherally situated hypoechoic tumor
would justify an operative strategy with frozen section examination and possibly
organ sparing surgery instead of orchiectomy.
PMID- 25140497
TI - Normal values for transbulbar sonography and magnetic resonance imaging of the
optic nerve sheath diameter (ONSD) in children and adolescents.
AB - PURPOSE: To establish normal values of the optic nerve sheath diameter (ONSD) in
children and adolescents for transbulbar sonography and magnetic resonance
imaging. MATERIALS AND METHODS: In 99 children and adolescents (age: 5.6 - 18.6
years, mean: 12 years) without neurologic or ophthalmologic disease, measurements
of the ONSD with transbulbar sonography were performed. For comparison 59
children and adolescents (age: 5.1 - 17.4 years, mean 12.3 years) with a normal
MR examination of the brain had measurements of the ONSD on a T2-weighted thin
section sequence of the orbit. Besides establishing modality-related normal
values, age dependency, accuracy and reproducibility of measurements were
assessed. RESULTS: Overall the mean ONSD was 5.75 +/- 0.52 mm for transbulbar
sonography and 5.69 +/- 0.31 mm for MRI. There was no statistical significance
between the 95 % percentiles and age for both transbulbar sonography (p = 0.332)
and MRI (p = 0.336). As a parameter for the reproducibility of measurements, the
repeatability coefficient (RC) was between 0.34 mm and 0.46 mm. The concordance
correlation coefficient (CCC) values revealed a high agreement between readers
both for transbulbar sonography (0.868) and MRI (0.796). CONCLUSION: Normal
values for ONSD in children and adolescents found in this study are significantly
higher than assumed. The values found for transbulbar sonography are confirmed by
comparable results for MR measurements. A precise sonographic measurement
technique and the consideration of normal values found hereby are essential for
correct interpretation of ONSD measurements in children and adolescents.
PMID- 25140498
TI - Noninvasive Prenatal Diagnosis of Hypohidrotic Ectodermal Dysplasia by Tooth Germ
Sonography.
AB - PURPOSE: Hypohidrotic ectodermal dysplasia, a potentially life-threatening
heritable disorder, may be recognized already in utero by characteristic features
such as oligodontia and mandibular hypoplasia. As therapeutic options and
prognosis depend on the time point of diagnosis, early recognition was attempted
during routine prenatal ultrasound examinations. SUBJECTS AND METHODS: Fetuses of
nine pregnant women (one triplet and eight singleton pregnancies) with family
histories of hypohidrotic ectodermal dysplasia were investigated by sonography
between the 20th and 24th week of gestation. RESULTS: In 4 male and 2 female
fetuses reduced amounts of tooth germs were detected, whereas 5 fetal subjects
showed the normal amount. Three-dimensional ultrasound evaluation revealed
mandibular hypoplasia in 5 of the 6 fetuses with oligodontia. Molecular genetic
analysis and/or clinical findings after birth confirmed the prenatal sonographic
diagnosis in each subject. CONCLUSION: In subjects with a family history of
hypohidrotic ectodermal dysplasia, the diagnosis of this rare condition can be
established noninvasively by sonography in the second trimester of pregnancy.
Early recognition of the disorder may help to prevent dangerous hyperthermic
episodes in infancy and may allow timely therapeutic interventions.
PMID- 25140499
TI - The scientific literature on Limnoperna fortunei (Dunker 1857) from 1982 to 2012.
AB - Limnoperna fortunei (golden mussel) is a freshwater bivalve native to Southeast
Asia, but is becoming an invasive species in several aquatic ecosystems in the
world. In this study, a scientometric analysis was performed to identify the
patterns, trends and gaps of knowledge for this invasive species. A survey of the
published literature was conducted using the database of the Thomson Institute
for Scientific Information (ISI). A total of 107 papers were surveyed that were
published between 1982 and 2012 in 60 journals. The number of papers on L.
fortunei over the years has increased, especially within the last eight years of
the study period. Argentina, Brazil, and Japan are the countries that contributed
the most papers to the literature on invasive bivalve. The majority of papers
were field-observational studies. Among some important gaps that need to be
addressed are the relatively small number and/or lack of studies conducted in the
native countries and in countries invaded by L. fortunei, the lack of
internationally collaborative publications in these countries, as well as a low
number of internationally collaborative studies.
PMID- 25140500
TI - Growth and intestinal morphology of juvenile pacu Piaractus mesopotamicus
(Holmberg 1887) fed dietary prebiotics (mannanoligosaccharides - MOS).
AB - Intensification of aquaculture production systems exposes fish to numerous
stressors, which may negatively affect their growth and limit profitability of
aquaculture systems. This study determined effects of increasing levels of
dietary mannanoligosaccharides on growth and intestine morphology of pacu. Fish
(44.04 g) were randomly distributed into 32 tanks (500 L; 10 fishes per tank) and
fed during 63 days with a commercial diet supplemented with 0.0; 0.2; 0.4; 0.6;
0.8; 1.0; 1.5 and 2.0% dietary mannanoligosaccharides. Growth parameters did not
differ (P>0.05) between fish fed control diet and mannanoligosaccharide
supplemented diets. Intestinal villi perimeter was performed in fish fed control
diet, 0.4 and 1.5% dietary mannanoligosaccharides and also showed no differences
(P>0.05) between treatments. Dietary supplementation of mannanoligosaccharides
unclear did not have effects on pacu. Studies on the characterization of
intestinal microbiota together with experiment that reproduce commercial fish
production systems rearing conditions are necessary to determine the effective
use of this dietary supplement for the species.
PMID- 25140501
TI - Magnetic Parkia pendula seed gum as matrix for Concanavalin A lectin
immobilization and its application in affinity purification.
AB - The present work aimed to magnetize Parkia pendula seeds gum and use it as a
matrix for Concanavalin A covalent immobilization. This composite was applied in
affinity purification of glycoconjugates. Parkia pendula seeds were hydrated and
the gum provenient from the supernatant was precipitated and washed with ethanol
and dried. The gum was magnetized in co-precipitation using solutions of Fe+2 and
Fe+3. Matrix activation was accomplished with NaIO4. Magnetized Parkia pendula
seeds gum with covalently immobilized Concanavalin A was used as an affinity
matrix for the recognition of bovine serum fetuin glycoprotein. Fetuin elution
was carried out with a solution of glucose (300mM) and evaluated through SDS
PAGE. The efficiency of lectin immobilization and fetuin purification were 63%
and 14%, respectively. These results indicate that the composite produced is a
promising magnetic polysaccharide matrix for lectins immobilization. Thus, such
system can be applied for affinity purification allowing an easy recovery by
magnetic field.
PMID- 25140502
TI - First ediacaran fauna occurrence in northeastern Brazil (jaibaras basin,
?ediacaran-cambrian): preliminary results and regional correlation.
AB - This study reports the first known occurrence of the Ediacaran fauna in
northeastern Brazil (at Pacuja Municipality, northwestern state of Ceara) and
presents preliminary interpretations of its significance. Regional correlation
indicates that the fossils originated in the Jaibaras Basin and that they may
represent a new geological system. The depositional environment can be attributed
to a fluviomarine system. Nine Ediacaran species can be identified, including
members of pandemic groups (e.g., Charniodiscus arboreus Glaessner, 1959;
?Charniodiscus concentricus Ford, 1958; Cyclomedusa davidi Sprigg, 1947;
Ediacaria flindersi Sprigg, 1947; and Medusinites asteroides Sprigg, 1949) and
endemic groups (e.g., Kimberella quadrata Glaessner & Wade, 1966;
Palaeophragmodictya reticulata Gehling & Rigby, 1996; Parvancorina minchami
Glaessner, 1958; and Pectinifrons abyssalis Bamforth, Narbonne, Anderson, 2008).
Three ichnogenera are also present: Arenicolites Salter, 1857; Palaeophycus Hall,
1987; and Planolites Nicholson, 1873. The relative age of the deposits is between
?Ediacaran and Cambrian, and the fauna resembles the White Sea Assemblage. The
bioturbation presents typical unbranched Ediacaran ichnogenera with little depth
in the substrate. This previously unknown occurrence of the Ediacaran fauna
reinforces the importance of the state of Ceara to Brazilian and global
palaeontology.
PMID- 25140503
TI - Thyroid gland development in Rachycentron canadum during early life stages.
AB - The aim of this study was to describe the ontogeny of thyroid follicles in cobia
Rachycentron canadum. Larvae were sampled daily (n=15 - 20) from hatching until
15 dah (days after hatching). Following, larvae were sampled every two days by 28
dah; a new sample was taken at 53 dah. The samples were dehydrated, embedded in
Paraplast, and sections of 3 um were dewaxed, rehydrated and stained with HE and
PAS. A single follicle was already present 1 dah and three follicles were found 8
dah. The number of follicles increased up to 19 on 53 dah. The diameter of
follicles and follicular cell height were lower 1 dah (6.83 +/- 1.00 and 4.6 +/-
0.01 um), but increased from 8 dah (24.03 +/- 0.46 um e 6.43 +/- 0.46 um). From 8
dah, the presence of reabsorption vesicles was observed in the colloid and from
the 19 dah some follicles did not present colloid. The early thyroid follicle
appearance in cobia larvae as well as the high quantity of follicles without
colloid and/or with vesicles even after the metamorphosis, might be the
explanation of the fast growth of the cobia.
PMID- 25140504
TI - Probiotics protect the intestinal wall of morphological changes caused by
malnutrition.
AB - This study sought to morphometrically analyze the jejunal wall of protein
malnourished rats administered a probiotic supplement. The sample consisted of
recently weaned Wistar rats (Rattus norvegicus) distributed among four groups:
animals given a commercial diet (G1, n = 4); animals given the same ration as G1
plus a probiotic supplement (G2, n = 4); animals given a 4% protein diet (G3, n =
4); and animals given the same ration as G3 plus a probiotic supplement (G4, n =
4). After 12 weeks, part of the jejunum was harvested and subjected to routine
histological processing. Transverse sections with a thickness of 3 um were
stained with HE, and histochemical techniques were used to assay for
glycoconjugates, including staining with periodic acid-Schiff (PAS) + diastase,
Alcian Blue (AB) solution at pH 2.5, and Alcian Blue solution at pH 1.0.
Morphometric analysis of the bowel wall showed that the probiotic culture used in
this study induced hypertrophy of several layers of the jejunal wall in well
nourished animals and reduced the bowel wall atrophy usually observed in protein
malnourished animals. Neither malnutrition nor the use of probiotics altered the
relationship between the number of goblet cells and the number of enterocytes.
PMID- 25140505
TI - Re-induction of desiccation tolerance after germination of Cedrela fissilis Vell.
seeds.
AB - This work aimed to characterize the re-induction of desiccation tolerance (DT) in
germinated seeds, using polyethylene glycol (PEG 8000). Cell changes were
investigated through cytological assays (cell viability and transmission
electronic microscopy) as well as DNA integrity during loss and re-establishment
of DT. The loss of DT was characterized by drying germinated seeds with different
radicle lengths (1, 2, 3, 4 and 5 mm) in silica gel, decreasing the moisture
content to ten percentage points intervals, followed by pre-humidification (100%
RH / 24 h) and rehydration. To re-induce DT, germinated seeds were treated for 72
h with PEG (-2.04 MPa) and PEG (-2.04 MPa) + ABA (100 uM) before dehydration.
Germinated seeds did not tolerate desiccation to 10% moisture content,
irrespectively of the radicle length. However, when incubated in PEG, those with
1 and 2 mm long radicle attained 71% and 29% survival, respectively. The PEG+ABA
treatment was efficient to re-establish DT in seeds with 1 mm long radicles (100%
survival). The ultrastructural assays of the cells of germinated seeds with 2 and
5 mm length confirmed the obtained physiological results. Germinated seeds of C.
fissilis constitute a useful tool for desiccation tolerance investigations.
PMID- 25140506
TI - CD56 antibody: old-fashioned or still trendy in endocrine lung tumors.
AB - BACKGROUND: In 2010, the World Health Organization published a new classification
of the endocrine tumors based on the mitotic rate and index. Concerning lung
endocrine tumors, the classification of 2004 remains acceptable and widely
approved. We noticed in many publications that the most used antibodies in these
tumors are chromogranin and synaptophysin. This finding let us wonder about the
diagnostic utility of the CD56 antibody which is widely used in our department.
MATERIAL AND METHODS: Sixty-nine endocrine lung cancers were diagnosed over a 12
month period in our Department of Pathology. Immunohistochemical technique using
the three antibodies: chromogranin, synaptophysin, and CD56 was performed. The
sensitivity of the three antibodies was performed using the ratio: true negative
cases/true negative cases + false positive cases. The specificity wasn't
performed because the antibodies were used only in endocrine tumors. The
comparison of the different percentages of expression of the three antibodies was
made by the SPSS software 22.0. RESULTS: The sensitivity of the chromogranin,
synpatophysin, and CD56 accounted for 69%, 77%, and 98%, respectively. The mean
percentage of immunoreactive cells with CD56 was 70% towards 15% and 20% with
chromogranin and synaptophysin antibodies, respectively. The comparison of the
percentages of expression showed a significant statistical difference between the
expression of CD56 versus synaptophysin and CD56 versus chromogranin with
P<0.001. CONCLUSION: CD56 antibody seems to be of diagnostic value in endocrine
lung tumors with the highest sensitivity. This fact highlights the necessity of
using it as a first-line neuroendocrine marker in association to chromogranin
which is considered as the most specific endocrine antibody.
PMID- 25140507
TI - Perioperative regional anesthesia fellowships: a blueprint for success.
PMID- 25140508
TI - Cervical paravertebral block for elbow and wrist surgery: the jury verdict may be
neither easy nor popular.
PMID- 25140509
TI - Evaluation of a task-specific checklist and global rating scale for ultrasound
guided regional anesthesia.
AB - Checklists and global rating scales (GRSs) are used for assessment of anesthesia
procedural skills. The purpose of this study was to evaluate the reliability and
validity of a recently proposed assessment tool comprising a checklist and GRS
specific for ultrasound-guided regional anesthesia. METHODS: In this prospective,
fully crossed study, we videotaped 30 single-target nerve block procedures
performed by anesthesia trainees. Following pilot assessment and observer
training, videos were assessed in random order by 6 blinded, expert observers.
Interrater reliability was evaluated with intraclass correlation coefficients
(ICCs) based on a 2-way random-effects model that took into account both
agreement and correlation between observer results. Construct validity and
feasibility were also evaluated. RESULTS: The ICC between assessors' total scores
was 0.44 (95% confidence interval, 0.27-0.62). All 6 observers scored
"experienced trainees" higher than "inexperienced trainees" (median total score
76.7 vs 54.2, P = 0.01), supporting the test's construct validity. The median
time to assess the videos was 4 minutes 29 seconds. CONCLUSIONS: This is the
first study to evaluate the reliability and validity of a combined checklist and
GRS for ultrasound-guided regional anesthesia using multiple observers and taking
into account both absolute agreement and correlation in determining the ICC of
0.44 for interrater reliability. There was evidence to support construct
validity.
PMID- 25140510
TI - Accuracy and consistency of modern elastomeric pumps.
AB - Continuous peripheral nerve blockade has become a popular method of achieving
postoperative analgesia for many surgical procedures. The safety and reliability
of infusion pumps are dependent on their flow rate accuracy and consistency.
Knowledge of pump rate profiles can help physicians determine which infusion pump
is best suited for their clinical applications and specific patient population.
Several studies have investigated the accuracy of portable infusion pumps. Using
methodology similar to that used by Ilfeld et al, we investigated the accuracy
and consistency of several current elastomeric pumps.
PMID- 25140511
TI - Pourfour du petit syndrome after supraclavicular catheter discontinuation.
PMID- 25140512
TI - Improving transversus abdominis plane block safety.
PMID- 25140513
TI - "Wrong side" sticker/dressing to help reduce wrong-sided nerve blocks.
PMID- 25140514
TI - Redefining the adductor canal block.
PMID- 25140515
TI - Generation and characterization of the first immortalized alpaca cell line
suitable for diagnostic and immunization studies.
AB - Raising of alpacas as exotic livestock for wool and meat production and as
companion animals is growing in importance in the United States, Europe and
Australia. Furthermore the alpaca, as well as the rest of the camelids, possesses
the peculiarity of producing single-chain antibodies from which nanobodies can be
generated. Nanobodies, due to their structural simplicity and reduced size, are
very versatile in terms of manipulation and bio-therapeutic exploitation. In fact
the biotech companies involved in nanobody production and application continue to
grow in number and size. Hence, the development of reagents and tools to assist
in the further growth of this new scientific and entrepreneurial reality is
becoming a necessity. These are needed mainly to address alpaca disease diagnosis
and prophylaxis, and to develop alpaca immunization strategies for nanobody
generation. For instance an immortalized alpaca cell line would be extremely
valuable. In the present work the first stabilized alpaca cell line from alpaca
skin stromal cells (ASSCs) was generated and characterized. This cell line was
shown to be suitable for replication of viruses bovine herpesvirus-1, bovine
viral diarrhea virus and caprine herpesvirus-1 and the endocellular parasite
Neospora caninum. Moreover ASSCs were easy to transfect and transduce by several
methods. These two latter characteristics are extremely useful when recombinant
antigens need to be produced in a host homologous system. This work could be
considered as a starting point for the expansion of the biotechnologies linked to
alpaca farming and industry.
PMID- 25140517
TI - The gait disorder in downbeat nystagmus syndrome.
AB - BACKGROUND: Downbeat nystagmus (DBN) is a common form of acquired fixation
nystagmus with key symptoms of oscillopsia and gait disturbance. Gait disturbance
could be a result of impaired visual feedback due to the involuntary ocular
oscillations. Alternatively, a malfunction of cerebellar locomotor control might
be involved, since DBN is considered a vestibulocerebellar disorder. METHODS:
Investigation of walking in 50 DBN patients (age 72 +/- 11 years, 23 females) and
50 healthy controls (HS) (age 70 +/- 11 years, 23 females) using a pressure
sensitive carpet (GAITRite). The patient cohort comprised subjects with only
ocular motor signs (DBN) and subjects with an additional limb ataxia (DBNCA).
Gait investigation comprised different walking speeds and walking with eyes
closed. RESULTS: In DBN, gait velocity was reduced (p<0.001) with a reduced
stride length (p<0.001), increased base of support (p<0.050), and increased
double support (p<0.001). Walking with eyes closed led to significant gait
changes in both HS and DBN. These changes were more pronounced in DBN patients
(p<0.001). Speed-dependency of gait variability revealed significant differences
between the subgroups of DBN and DBNCA (p<0.050). CONCLUSIONS: (I) Impaired
visual control caused by involuntary ocular oscillations cannot sufficiently
explain the gait disorder. (II) The gait of patients with DBN is impaired in a
speed dependent manner. (III) Analysis of gait variability allows distinguishing
DBN from DBNCA: Patients with pure DBN show a speed dependency of gait
variability similar to that of patients with afferent vestibular deficits. In
DBNCA, gait variability resembles the pattern found in cerebellar ataxia.
PMID- 25140518
TI - Microglial AGE-albumin is critical in promoting alcohol-induced neurodegeneration
in rats and humans.
AB - Alcohol is a neurotoxic agent, since long-term heavy ingestion of alcohol can
cause various neural diseases including fetal alcohol syndrome, cerebellar
degeneracy and alcoholic dementia. However, the molecular mechanisms of alcohol
induced neurotoxicity are still poorly understood despite numerous studies. Thus,
we hypothesized that activated microglial cells with elevated AGE-albumin levels
play an important role in promoting alcohol-induced neurodegeneration. Our
results revealed that microglial activation and neuronal damage were found in the
hippocampus and entorhinal cortex following alcohol treatment in a rat model.
Increased AGE-albumin synthesis and secretion were also observed in activated
microglial cells after alcohol exposure. The expressed levels of receptor for AGE
(RAGE)-positive neurons and RAGE-dependent neuronal death were markedly elevated
by AGE-albumin through the mitogen activated protein kinase pathway. Treatment
with soluble RAGE or AGE inhibitors significantly diminished neuronal damage in
the animal model. Furthermore, the levels of activated microglial cells, AGE
albumin and neuronal loss were significantly elevated in human brains from
alcoholic indivisuals compared to normal controls. Taken together, our data
suggest that increased AGE-albumin from activated microglial cells induces
neuronal death, and that efficient regulation of its synthesis and secretion is a
therapeutic target for preventing alcohol-induced neurodegeneration.
PMID- 25140519
TI - Asante Calcium Green and Asante Calcium Red--novel calcium indicators for two
photon fluorescence lifetime imaging.
AB - For a comprehensive understanding of cellular processes and potential
dysfunctions therein, an analysis of the ubiquitous intracellular second
messenger calcium is of particular interest. This study examined the suitability
of the novel Ca2+-sensitive fluorescent dyes Asante Calcium Red (ACR) and Asante
Calcium Green (ACG) for two-photon (2P)-excited time-resolved fluorescence
measurements. Both dyes displayed sufficient 2P fluorescence excitation in a
range of 720-900 nm. In vitro, ACR and ACG exhibited a biexponential fluorescence
decay behavior and the two decay time components in the ns-range could be
attributed to the Ca(2+)-free and Ca(2+)-bound dye species. The amplitude
weighted average fluorescence decay time changed in a Ca(2+)-dependent way,
unraveling in vitro dissociation constants K(D) of 114 nM and 15 nM for ACR and
ACG, respectively. In the presence of bovine serum albumin, the absorption and
steady-state fluorescence behavior of ACR was altered and its biexponential
fluorescence decay showed about 5-times longer decay time components indicating
dye-protein interactions. Since no ester derivative of ACG was commercially
available, only ACR was evaluated for 2P-excited fluorescence lifetime imaging
microscopy (2P-FLIM) in living cells of American cockroach salivary glands. In
living cells, ACR also exhibited a biexponential fluorescence decay with clearly
resolvable short (0.56 ns) and long (2.44 ns) decay time components attributable
to the Ca(2+)-free and Ca(2+)-bound ACR species. From the amplitude-weighted
average fluorescence decay times, an in situ K(D) of 180 nM was determined. Thus,
quantitative [Ca(2+)]i recordings were realized, unraveling a reversible dopamine
induced [Ca(2+)]i elevation from 21 nM to 590 nM in salivary duct cells. It was
concluded that ACR is a promising new Ca(2+) indicator dye for 2P-FLIM recordings
applicable in diverse biological systems.
PMID- 25140520
TI - Metagenomic survey for viruses in Western Arctic caribou, Alaska, through
iterative assembly of taxonomic units.
AB - Pathogen surveillance in animals does not provide a sufficient level of vigilance
because it is generally confined to surveillance of pathogens with known economic
impact in domestic animals and practically nonexistent in wildlife species. As
most (re-)emerging viral infections originate from animal sources, it is
important to obtain insight into viral pathogens present in the wildlife
reservoir from a public health perspective. When monitoring living, free-ranging
wildlife for viruses, sample collection can be challenging and availability of
nucleic acids isolated from samples is often limited. The development of viral
metagenomics platforms allows a more comprehensive inventory of viruses present
in wildlife. We report a metagenomic viral survey of the Western Arctic herd of
barren ground caribou (Rangifer tarandus granti) in Alaska, USA. The presence of
mammalian viruses in eye and nose swabs of 39 free-ranging caribou was
investigated by random amplification combined with a metagenomic analysis
approach that applied exhaustive iterative assembly of sequencing results to
define taxonomic units of each metagenome. Through homology search methods we
identified the presence of several mammalian viruses, including different
papillomaviruses, a novel parvovirus, polyomavirus, and a virus that potentially
represents a member of a novel genus in the family Coronaviridae.
PMID- 25140521
TI - Associations between longer habitual day napping and non-alcoholic fatty liver
disease in an elderly Chinese population.
AB - CONTEXT: Both longer habitual day napping and Non-Alcoholic Fatty Liver Disease
(NAFLD) are associated with diabetes and inflammation, but the association
between day napping and NAFLD remains unexplored. OBJECTIVE: To investigate the
association between the duration of habitual day napping and NAFLD in an elderly
Chinese population and to gain insight into the role of inflammatory cytokines in
this association. DESIGN AND SETTING: We conducted a series of cross-sectional
studies of the community population in Chongqing, China, from 2011 to 2012.
PARTICIPANTS: Among 6998 participants aged 40 to 75 years, 6438 eligible
participants were included in the first study and analyzed to observe the
association between day napping duration and NAFLD. In a separate study, 80 non
nappers and 90 nappers were selected to identify the role of inflammatory
cytokines in this association. Logistic regression models were used to examine
the odds ratios (ORs) of day nap duration with NAFLD. RESULTS: Day nappers had a
significantly higher prevalence of NAFLD (P<0.001). Longer day napping duration
was associated in a dose-dependent manner with NAFLD (P trend <0.001). After
adjustment for potential confounders, the ORs were 1.67 (95% CI 1.13-2.46) for
those reporting 0.5-1 h and 1.49 (95% CI 1.01-2.19) for those reporting >1 h of
day napping compared with individuals who did not take day naps (all P<0.05).
Longer-duration day nappers had higher levels of IL-6 and progranulin (PGRN) but
lower levels of Secreted frizzled-related protein-5 (SFRP5, all P trend <0.001).
After adjusting for IL-6, PGRN, and SFRP5, the association between day napping
duration and NAFLD disappeared (all P>0.05). CONCLUSION: Longer day napping
duration is associated with a higher prevalence of NAFLD, and inflammatory
cytokines may be an essential link between day napping and NAFLD.
PMID- 25140522
TI - Development of on-chip multi-imaging flow cytometry for identification of imaging
biomarkers of clustered circulating tumor cells.
AB - An on-chip multi-imaging flow cytometry system has been developed to obtain
morphometric parameters of cell clusters such as cell number, perimeter, total
cross-sectional area, number of nuclei and size of clusters as "imaging
biomarkers", with simultaneous acquisition and analysis of both bright-field (BF)
and fluorescent (FL) images at 200 frames per second (fps); by using this system,
we examined the effectiveness of using imaging biomarkers for the identification
of clustered circulating tumor cells (CTCs). Sample blood of rats in which a
prostate cancer cell line (MAT-LyLu) had been pre-implanted was applied to a
microchannel on a disposable microchip after staining the nuclei using
fluorescent dye for their visualization, and the acquired images were measured
and compared with those of healthy rats. In terms of the results, clustered cells
having (1) cell area larger than 200 um2 and (2) nucleus area larger than 90 um2
were specifically observed in cancer cell-implanted blood, but were not observed
in healthy rats. In addition, (3) clusters having more than 3 nuclei were
specific for cancer-implanted blood and (4) a ratio between the actual perimeter
and the perimeter calculated from the obtained area, which reflects a shape
distorted from ideal roundness, of less than 0.90 was specific for all clusters
having more than 3 nuclei and was also specific for cancer-implanted blood. The
collected clusters larger than 300 um2 were examined by quantitative gene copy
number assay, and were identified as being CTCs. These results indicate the
usefulness of the imaging biomarkers for characterizing clusters, and all of the
four examined imaging biomarkers-cluster area, nuclei area, nuclei number, and
ratio of perimeter-can identify clustered CTCs in blood with the same level of
preciseness using multi-imaging cytometry.
PMID- 25140524
TI - Is rumination after bereavement linked with loss avoidance? Evidence from eye
tracking.
AB - Rumination is a risk factor in adjustment to bereavement. It is associated with
and predicts psychopathology after loss. Yet, the function of rumination in
bereavement remains unclear. In the past, researchers often assumed rumination to
be a maladaptive confrontation process. However, based on cognitive avoidance
theories of worry in generalised anxiety disorder (GAD) and rumination after post
traumatic stress disorder (PTSD), others have suggested that rumination may serve
to avoid painful aspects of the loss, thereby contributing to complicated grief.
To examine if rumination is linked with loss avoidance, an eye-tracking study was
conducted with 54 bereaved individuals (27 high and 27 low ruminators). On 24
trials, participants looked for 10 seconds at a picture of the deceased and a
picture of a stranger, randomly combined with negative, neutral or loss-related
words. High ruminators were expected to show initial vigilance followed by
subsequent disengagement for loss stimuli (i.e., picture deceased with a loss
word) in the first 1500 ms. Additionally, we expected high ruminators to avoid
these loss stimuli and to show attentional preference for non-loss-related
negative stimuli (i.e., picture stranger with a negative word) on longer exposure
durations (1500-10000 ms). Contrary to expectations, we found no evidence for an
effect of rumination on vigilance and disengagement of loss stimuli in the first
1500 ms. However, in the 1500-10000 ms interval, high ruminators showed shorter
gaze times for loss stimuli and longer gaze times for negative (and neutral) non
loss-related stimuli, even when controlling for depression and complicated grief
symptom levels. Effects of rumination on average fixation times mirrored these
findings. This suggests that rumination and loss avoidance are closely
associated. A potential clinical implication is that rumination and grief
complications after bereavement may be reduced through the use of exposure and
acceptance-based therapeutic techniques.
PMID- 25140523
TI - Does mortality vary between Asian subgroups in New Zealand: an application of
hierarchical Bayesian modelling.
AB - The aim of this paper was to see whether all-cause and cause-specific mortality
rates vary between Asian ethnic subgroups, and whether overseas born Asian
subgroup mortality rate ratios varied by nativity and duration of residence. We
used hierarchical Bayesian methods to allow for sparse data in the analysis of
linked census-mortality data for 25-75 year old New Zealanders. We found directly
standardised posterior all-cause and cardiovascular mortality rates were highest
for the Indian ethnic group, significantly so when compared with those of Chinese
ethnicity. In contrast, cancer mortality rates were lowest for ethnic Indians.
Asian overseas born subgroups have about 70% of the mortality rate of their New
Zealand born Asian counterparts, a result that showed little variation by Asian
subgroup or cause of death. Within the overseas born population, all-cause
mortality rates for migrants living 0-9 years in New Zealand were about 60% of
the mortality rate of those living more than 25 years in New Zealand regardless
of ethnicity. The corresponding figure for cardiovascular mortality rates was
50%. However, while Chinese cancer mortality rates increased with duration of
residence, Indian and Other Asian cancer mortality rates did not. Future research
on the mechanisms of worsening of health with increased time spent in the host
country is required to improve the understanding of the process, and would assist
the policy-makers and health planners.
PMID- 25140525
TI - Thermal, chemical and pH induced unfolding of turmeric root lectin: modes of
denaturation.
AB - Curcuma longa rhizome lectin, of non-seed origin having antifungal, antibacterial
and alpha-glucosidase inhibitory activities, forms a homodimer with high thermal
stability as well as acid tolerance. Size exclusion chromatography and dynamic
light scattering show it to be a dimer at pH 7, but it converts to a monomer near
pH 2. Circular dichroism spectra and fluorescence emission maxima are virtually
indistinguishable from pH 7 to 2, indicating secondary and tertiary structures
remain the same in dimer and monomer within experimental error. The tryptophan
environment as probed by acrylamide quenching data yielded very similar data at
pH 2 and pH 7, implying very similar folding for monomer and dimer. Differential
scanning calorimetry shows a transition at 350.3 K for dimer and at 327.0 K for
monomer. Thermal unfolding and chemical unfolding induced by guanidinium chloride
for dimer are both reversible and can be described by two-state models. The
temperatures and the denaturant concentrations at which one-half of the protein
molecules are unfolded, are protein concentration-dependent for dimer but protein
concentration-independent for monomer. The free energy of unfolding at 298 K was
found to be 5.23 Kcal mol-1 and 14.90 Kcal mol-1 for the monomer and dimer
respectively. The value of change in excess heat capacity upon protein
denaturation (DeltaCp) is 3.42 Kcal mol-1 K-1 for dimer. The small DeltaCp for
unfolding of CLA reflects a buried hydrophobic core in the folded dimeric
protein. These unfolding experiments, temperature dependent circular dichroism
and dynamic light scattering for the dimer at pH 7 indicate its higher stability
than for the monomer at pH 2. This difference in stability of dimeric and
monomeric forms highlights the contribution of inter-subunit interactions in the
former.
PMID- 25140528
TI - Integrating basic science without integrating basic scientists: reconsidering the
place of individual teachers in curriculum reform.
AB - The call for integration of the basic and clinical sciences plays prominently in
recent conversations about curricular change in medical education; however,
history shows that, like other concepts related to curricular reform, integration
has been continually revisited, leading to incremental change but no meaningful
transformation. To redress this cycle of "change without difference," the medical
education community must reexamine the approach that dominates medical education
reform efforts and explore alternative perspectives that may help to resolve the
cyclical "problem" of recommending but not effecting integration. To provide a
different perspective on implementing integration, the authors of this
Perspective look to the domain of educational change as an approach to examining
the transitions that occur within complex and evolving environments. This area of
literature both acknowledges the multiple levels involved in change and
emphasizes the need not only to address systemic structure but also to prioritize
individuals during times of transition. The struggle to implement curricular
integration in medical education may stem from the fact that reform efforts
appear to focus largely on transformation at the level of curricular structure as
opposed to considering what learning needs to occur at each level of change and
highlighting the individual as the educational change literature suggests. To
bring appropriate attention to the place of individual educators, especially
basic scientists, the medical education community should explore how the mandate
to integrate clinically relevant material may impact these faculty and the
teaching of their domains.
PMID- 25140527
TI - Transforming growth factor-beta1 signaling represses testicular steroidogenesis
through cross-talk with orphan nuclear receptor Nur77.
AB - Transforming growth factor- beta1 (TGF-beta1) has been reported to inhibit
luteinizing hormone (LH) mediated-steroidogenesis in testicular Leydig cells.
However, the mechanism by which TGF-beta1 controls the steroidogenesis in Leydig
cells is not well understood. Here, we investigated the possibility that TGF
beta1 represses steroidogenesis through cross-talk with the orphan nuclear
receptor Nur77. Nur77, which is induced by LH/cAMP signaling, is one of major
transcription factors that regulate the expression of steroidogenic genes in
Leydig cells. TGF-beta1 signaling inhibited cAMP-induced testosterone production
and the expression of steroidogenic genes such as P450c17, StAR and 3beta-HSD in
mouse Leydig cells. Further, TGF-beta1/ALK5 signaling repressed cAMP-induced and
Nur77-activated promoter activity of steroidogenic genes. In addition, TGF
beta1/ALK5-activated Smad3 repressed Nur77 transactivation of steroidogenic gene
promoters by interfering with Nur77 binding to DNA. In primary Leydig cells
isolated from Tgfbr2flox/flox Cyp17iCre mice, TGF-beta1-mediated repression of
cAMP-induced steroidogenic gene expression was significantly less than that in
primary Leydig cells from Tgfbr2flox/flox mice. Taken together, these results
suggest that TGF-beta1/ALK5/Smad3 signaling represses the expression of
steroidogenic genes via the suppression of Nur77 transactivation in testicular
Leydig cells. These findings may provide a molecular mechanism involved in the
TGF-beta1-mediated repression of testicular steroidogenesis.
PMID- 25140529
TI - A quantitative linguistic analysis of National Institutes of Health R01
application critiques from investigators at one institution.
AB - PURPOSE: Career advancement in academic medicine often hinges on the ability to
garner research funds. The National Institutes of Health's (NIH's) R01 award is
the "gold standard" of an independent research program. Studies show
inconsistencies in R01 reviewers' scoring and in award outcomes for certain
applicant groups. Consistent with the NIH recommendation to examine potential
bias in R01 peer review, the authors performed a text analysis of R01 reviewers'
critiques. METHOD: The authors collected 454 critiques (262 from 91 unfunded and
192 from 67 funded applications) from 67 of 76 (88%) R01 investigators at the
University of Wisconsin-Madison with initially unfunded applications subsequently
funded between December 2007 and May 2009. To analyze critiques, the authors
developed positive and negative grant application evaluation word categories and
selected five existing categories relevant to grant review. They analyzed results
with linear mixed-effects models for differences due to applicant and application
characteristics. RESULTS: Critiques of funded applications contained more
positive descriptors and superlatives and fewer negative evaluation words than
critiques of unfunded applications. Experienced investigators' critiques
contained more references to competence. Critiques showed differences due to
applicant sex despite similar application scores or funding outcomes: more praise
for applications from female investigators, greater reference to
competence/ability for funded applications from female experienced investigators,
and more negative evaluation words for applications from male investigators (all
P<.05). CONCLUSIONS: Results suggest that text analysis is a promising tool for
assessing consistency in R01 reviewers' judgments, and gender stereotypes may
operate in R01 review.
PMID- 25140530
TI - Refocusing medical education reform: beyond the how.
AB - Integration of the basic and clinical sciences has been at the heart of medical
education reform efforts for nearly a century. Neither the rate nor magnitude of
actual progress suggests that reform is anywhere near completion, which presents
a challenge to educators to seek ways to overcome significant obstacles to
change. Robin Hopkins and colleagues, authors of the Perspective in this issue of
Academic Medicine that has prompted this invited Commentary, are among those
proposing interesting and useful answers to why integration has not been better
achieved. This Commentary affirms the importance of finding better ways to
accomplish curricular reform, while contending that real curricular reform must
move well beyond the integration of basic and clinical sciences. Drawing from the
2014 report of the Robert Wood Johnson Foundation's Commission to Build a
Healthier America, the authors cite evidence of significant disparities and
growing health challenges facing Americans today. They discuss three key
recommendations from the report: attending to early childhood experiences,
providing healthy choices within communities, and, particularly, rethinking the
education of health professionals. Next, the authors detail the implications of
these recommendations for medical education, stressing both the urgency and
importance of moving to adopt these as directions for real reform that will
address today's health care challenges.
PMID- 25140531
TI - Educating the educators: a key to curricular integration.
AB - According to Hopkins and colleagues, integration of basic science and clinical
practice in the medical curriculum has been "incremental" at best, rather than
transformative, in part because of a lack of focus on the individuals central to
the integration--basic science educators. These authors maintain that those who
lead change in education should not only address the systemic structure but also
understand the meaning of integration for individual basic scientists at
different levels of change. Their view has merit, and this Commentary author
suggests three concrete steps that institutions should undertake to engage basic
scientists who are interested in becoming "educationally literate" and assuming
leadership roles in curriculum integration: (1) Offer opportunities to help
interested basic science teaching faculty gain the necessary expertise to become
skilled educators; (2) establish institutional programs and structures that
foster a community of medical educators across departments and schools; and (3)
align institutional priorities and incentives to promote, rather than hinder,
integration in medical education. In essence, curricular integration cannot
succeed if the participants do not understand the "language of education."
Furthermore, faculty who opt for an education-focused career path should be
brought together from across departments, centers, and schools to create a
community of educators within the academic health center. Finally, institutional
leaders should place high value and proper incentives in terms of recognition and
opportunities for faculty advancement to ensure that those opting to gain
additional training as skilled educators will drive innovation and help move
curricular reform from incremental change to transformation.
PMID- 25140532
TI - An efficient approach for differentiating Alzheimer's disease from normal elderly
based on multicenter MRI using gray-level invariant features.
AB - Machine learning techniques, along with imaging markers extracted from structural
magnetic resonance images, have been shown to increase the accuracy to
differentiate patients with Alzheimer's disease (AD) from normal elderly
controls. Several forms of anatomical features, such as cortical volume, shape,
and thickness, have demonstrated discriminative capability. These approaches rely
on accurate non-linear image transformation, which could invite several nuisance
factors, such as dependency on transformation parameters and the degree of
anatomical abnormality, and an unpredictable influence of residual registration
errors. In this study, we tested a simple method to extract disease-related
anatomical features, which is suitable for initial stratification of the
heterogeneous patient populations often encountered in clinical data. The method
employed gray-level invariant features, which were extracted from linearly
transformed images, to characterize AD-specific anatomical features. The
intensity information from a disease-specific spatial masking, which was linearly
registered to each patient, was used to capture the anatomical features. We
implemented a two-step feature selection for anatomic recognition. First, a
statistic-based feature selection was implemented to extract AD-related
anatomical features while excluding non-significant features. Then, seven
knowledge-based ROIs were used to capture the local discriminative powers of
selected voxels within areas that were sensitive to AD or mild cognitive
impairment (MCI). The discriminative capability of the proposed feature was
measured by its performance in differentiating AD or MCI from normal elderly
controls (NC) using a support vector machine. The statistic-based feature
selection, together with the knowledge-based masks, provided a promising solution
for capturing anatomical features of the brain efficiently. For the analysis of
clinical populations, which are inherently heterogeneous, this approach could
stratify the large amount of data rapidly and could be combined with more
detailed subsequent analyses based on non-linear transformation.
PMID- 25140534
TI - Cationic poly(amidoamine) dendrimers induced cyto-protective autophagy in
hepatocellular carcinoma cells.
AB - Poly(amidoamine) (PAMAM) dendrimers are proposed as one of the most promising
nanomaterials for biomedical applications because of their unique tree-like
structure, monodispersity and tunable properties. In this study, we found that
PAMAM dendrimers could induce the formation of autophagosomes and the conversion
of microtubule-associated protein 1 light chain 3 (LC3) in hepatocellular
carcinoma HepG2 cells, while the inhibition of the Akt/mTOR and activation of the
Erk 1/2 signaling pathways were involved in autophagy-induced by PAMAM
dendrimers. We also investigated the suppression of autophagy with the obviously
enhanced cytotoxicity of PAMAM dendrimers. Moreover, the blockage of a reactive
oxygen species (ROS) could enhance the growth inhibition and apoptosis of
hepatocellular carcinoma cells, induced by PAMAM dendrimers through reducing
autophagic effects. Taken together, these findings explored the role and
mechanism of autophagy induced by PAMAM dendrimers in HepG2 cells, provided new
insight into the effect of autophagy on drug delivery nanomaterials and tumor
cells and contributed to the use of a drug delivery vehicle for hepatocellular
carcinoma treatment.
PMID- 25140535
TI - Oral delivery mediated RNA interference of a carboxylesterase gene results in
reduced resistance to organophosphorus insecticides in the cotton Aphid, Aphis
gossypii Glover.
AB - BACKGROUND: RNA interference (RNAi) is an effective tool to examine the function
of individual genes. Carboxylesterases (CarE, EC 3.1.1.1) are known to play
significant roles in the metabolism of xenobiotic compounds in many insect
species. Previous studies in our laboratory found that CarE expression was up
regulated in Aphis gossypii (Glover) (Hemiptera: Aphididae) adults of both
omethoate and malathion resistant strains, indicating the potential involvement
of CarE in organophosphorus (OP) insecticide resistance. Functional analysis
(RNAi) is therefore warranted to investigate the role of CarE in A. gossypii to
OPs resistance. RESULT: CarE expression in omethoate resistant individuals of
Aphis gossypii was dramatically suppressed following ingestion of dsRNA-CarE. The
highest knockdown efficiency (33%) was observed at 72 h after feeding when dsRNA
CarE concentration was 100 ng/uL. The CarE activities from the CarE knockdown
aphids were consistent with the correspondingly significant reduction in CarE
expression. The CarE activity in the individuals of control aphids was
concentrated in the range of 650-900 mOD/per/min, while in the individuals of
dsRNA-CarE-fed aphids, the CarE activity was concentrated in the range of 500-800
mOD/per/min. In vitro inhibition experiments also demonstrated that total CarE
activity in the CarE knockdown aphids decreased significantly as compared to
control aphids. Bioassay results of aphids fed dsRNA-CarE indicated that
suppression of CarE expression increased susceptibility to omethoate in
individuals of the resistant aphid strains. CONCLUSION: The results of this study
not only suggest that ingestion of dsRNA through artificial diet could be
exploited for functional genomic studies in cotton aphids, but also indicate that
CarE can be considered as a major target of organophosphorus insecticide (OPs)
resistance in A. gossypii. Further, our results suggest that the CarE would be a
propitious target for OPs resistant aphid control, and insect-resistant
transgenic plants may be obtained through plant RNAi-mediated silencing of insect
CarE expression.
PMID- 25140536
TI - The influence of pressure on the intrinsic dissolution rate of amorphous
indomethacin.
AB - New drug candidates increasingly tend to be poorly water soluble. One approach to
increase their solubility is to convert the crystalline form of a drug into the
amorphous form. Intrinsic dissolution testing is an efficient standard method to
determine the intrinsic dissolution rate (IDR) of a drug and to test the
potential dissolution advantage of the amorphous form. However, neither the
United States Pharmacopeia (USP) nor the European Pharmacopeia (Ph.Eur) state
specific limitations for the compression pressure in order to obtain compacts for
the IDR determination. In this study, the influence of different compression
pressures on the IDR was determined from powder compacts of amorphous (ball
milling) indomethacin (IND), a glass solution of IND and poly(vinylpyrrolidone)
(PVP) and crystalline IND. Solid state properties were analyzed with X-ray powder
diffraction (XRPD) and the final compacts were visually observed to study the
effects of compaction pressure on their surface properties. It was found that
there is no significant correlation between IDR and compression pressure for
crystalline IND and IND-PVP. This was in line with the observation of similar
surface properties of the compacts. However, compression pressure had an impact
on the IDR of pure amorphous IND compacts. Above a critical compression pressure,
amorphous particles sintered to form a single compact with dissolution properties
similar to quench-cooled disc and crystalline IND compacts. In such a case, the
apparent dissolution advantage of the amorphous form might be underestimated. It
is thus suggested that for a reasonable interpretation of the IDR, surface
properties of the different analyzed samples should be investigated and for
amorphous samples the IDR should be measured also as a function of the
compression pressure used to prepare the solid sample for IDR testing.
PMID- 25140533
TI - Quantifying the role of adverse events in the mortality difference between first
and second-generation antipsychotics in older adults: systematic review and meta
synthesis.
AB - BACKGROUND: Observational studies have reported higher mortality among older
adults treated with first-generation antipsychotics (FGAs) versus second
generation antipsychotics (SGAs). A few studies examined risk for medical events,
including stroke, ventricular arrhythmia, venous thromboembolism, myocardial
infarction, pneumonia, and hip fracture. OBJECTIVES: 1) Review robust
epidemiologic evidence comparing mortality and medical event risk between FGAs
and SGAs in older adults; 2) Quantify how much these medical events explain the
observed mortality difference between FGAs and SGAs. DATA SOURCES: Pubmed and
Science Citation Index. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND
INTERVENTIONS: Studies of antipsychotic users that: 1) evaluated mortality or
medical events specified above; 2) restricted to populations with a mean age of
65 years or older 3) compared FGAs to SGAs, or both to a non-user group; (4)
employed a "new user" design; (5) adjusted for confounders assessed prior to
antipsychotic initiation; (6) and did not require survival after antipsychotic
initiation. A separate search was performed for mortality estimates associated
with the specified medical events. STUDY APPRAISAL AND SYNTHESIS METHODS: For
each medical event, we used a non-parametric model to estimate lower and upper
bounds for the proportion of the mortality difference-comparing FGAs to SGAs
mediated by their difference in risk for the medical event. RESULTS: We provide a
brief, updated summary of the included studies and the biological plausibility of
these mechanisms. Of the 1122 unique citations retrieved, we reviewed 20
observational cohort studies that reported 28 associations. We identified hip
fracture, stroke, myocardial infarction, and ventricular arrhythmias as potential
intermediaries on the causal pathway from antipsychotic type to death. However,
these events did not appear to explain the entire mortality difference.
CONCLUSIONS: The current literature suggests that hip fracture, stroke,
myocardial infarction, and ventricular arrhythmias partially explain the
mortality difference between SGAs and FGAs.
PMID- 25140537
TI - "Push-Through" Rod Passage Technique for the Improvement of Lumbar Lordosis and
Sagittal Balance in Minimally Invasive Adult Degenerative Scoliosis Surgery.
AB - OF BACKGROUND DATA: Traditional open surgical techniques for correction of adult
degenerative scoliosis (ADS) are often associated with increased blood loss,
postoperative pain, and complications. Minimally invasive (MIS) techniques have
been utilized to address these issues; however, concerns regarding improving
certain alignment parameters have been raised. OBJECTIVE: A new "push-through"
technique for MIS correction of ADS has been developed wherein a rod is bent
before its placement into the screw heads and then contoured further to yield
improved correction of radiographic parameters. METHODS AND STUDY DESIGN:
Preoperative and postoperative radiographic measurements of 3 patients who
underwent MIS correction of scoliosis using the "push-through" technique were
compared with 22 prior patients who had received traditional MIS correction. All
patients received staged correction of scoliosis. The first stage involved
insertion of lateral lumbar interbodies. Standing x-rays were then evaluated for
overall global balance. The second stage involved appropriate MIS facetectomies,
facet fusions, posterior transforaminal interbodies at lower lumbar segments, and
finally the placement of rods.TECHNIQUE OVERVIEW:: (1) A long rod composed of
titanium is bent with a mild lordosis and passed through the extensions of the
screw heads cephalad to caudad. (2) The rod is passed fully through the incision
so it extrudes from the caudal end of the construct. At this point, further
lordosis is bent into the rods. (3) The rod is then pulled back into the
appropriate position. (4) The unnecessary cephalad rod is then cut to appropriate
length with a circular saw. (5) Rod reducers are then sequentially lowered and
tightened to achieve the desired correction. RESULTS: Mean age for all patients
was 66.02 years. Preoperative coronal Cobb, sagittal vertical axis (SVA), and
pelvic incidence (PI) were similar in all patients, whereas lumbar lordosis (LL)
was smaller (15.27 vs. 29.85 degrees, P=0.00389) and pelvic tilt (PT) was larger
(37.00 vs. 27.00 degrees, P=0.00011) in "push-through" patients. Postoperatively,
"pushthrough" patients experienced greater correction of LL (21.93 vs. 3.70
degrees, P=0.00001), PI-LL (-18.57 vs. -0.26 degrees, P=0.00471), PT (-7.67 vs.
0.40 degrees, P=0.00341), SVA (-40.67 mm vs. 0.95 mm, P=0.05846), and coronal
Cobb (-20.23 vs. -18.76 degrees, P=0.75). CONCLUSIONS: This new method of
contouring a rod enables improved LL. This technique is easy to perform and can
be a valuable tool in treating ADS using MIS techniques.
PMID- 25140538
TI - Bioreactor droplets from liposome-stabilized all-aqueous emulsions.
AB - Artificial bioreactors are desirable for in vitro biochemical studies and as
protocells. A key challenge is maintaining a favourable internal environment
while allowing substrate entry and product departure. We show that semipermeable,
size-controlled bioreactors with aqueous, macromolecularly crowded interiors can
be assembled by liposome stabilization of an all-aqueous emulsion. Dextran-rich
aqueous droplets are dispersed in a continuous polyethylene glycol (PEG)-rich
aqueous phase, with coalescence inhibited by adsorbed ~130-nm diameter liposomes.
Fluorescence recovery after photobleaching and dynamic light scattering data
indicate that the liposomes, which are PEGylated and negatively charged, remain
intact at the interface for extended time. Inter-droplet repulsion provides
electrostatic stabilization of the emulsion, with droplet coalescence prevented
even for submonolayer interfacial coatings. RNA and DNA can enter and exit
aqueous droplets by diffusion, with final concentrations dictated by
partitioning. The capacity to serve as microscale bioreactors is established by
demonstrating a ribozyme cleavage reaction within the liposome-coated droplets.
PMID- 25140539
TI - Detection of a right carotid focus of 18F-FDG predicted an ischemic stroke.
AB - A 60-year-old woman was referred into our department for staging of an
endometrial carcinoma. In addition to peritoneal and nodes metastases, F-FDG
PET/CT showed a calcified plaque of the right carotid with focal uptake. One
month later, the patient presented left hemiparesis, suggesting a right
hemisphere stroke. MRI confirmed frontal infarction in the anterior cerebral
artery territory. F-FDG is suggested to be a valuable tool to detect vessel wall
inflammation; detection of focal arterial uptake on PET/CT suggests unstable
plaque and requires urgent patient's management to prevent vascular events in a
population already weakened by both disease and therapy.
PMID- 25140540
TI - CyberKnife radiosurgery planning of a secreting pituitary adenoma performed with
68Ga DOTATATE PET and MRI.
AB - The images of a patient with acromegaly, who previously underwent operation for
pituitary adenoma, were obtained. The MRI scan showed a mass in the right
cavernous sinus, with biochemical test results positive for the presence of a
hormonally active adenoma. The patient was scheduled for CyberKnife radiotherapy.
Radiotherapy planning was carried out using MRI and PET/CT scan with somatostatin
analog 68Ga DOTATATE. The latter showed radiopharmaceutical uptake on the
adenomatous residual mass. Contours were drawn on MRI and PET images and were
summed up to devise the radiotherapy plan. The patient was treated with a total
dose of 24 Gy.
PMID- 25140541
TI - 18F-FDG PET/CT in anti-LGI1 encephalitis: initial and follow-up findings.
AB - Anti-LGI1 encephalitis is a subgroup of autoimmune encephalitis, characterized by
memory impairments, seizures, and behavioral problems. The diagnosis can be made
by clinical manifestation with a help of serum autoantibody test. There was lack
of imaging studies to evaluate and monitor the disease activity by anatomical and
functional information. Here, we report serial F-FDG PET/CT findings in a patient
with anti-LGI1 encephalitis. Intense F-FDG uptake was initially noted in
bilateral limbic system at active disease status, and then decreased and
eventually normalized according to the clinical improvement after treatment. F
FDG PET/CT can be used to evaluate treatment response of encephalitis.
PMID- 25140543
TI - 18F-FDG PET/CT demonstrating primary bone lymphoma of the extremities mimicking
an inflammatory peripheral arthropathy.
AB - A 66-year-old woman presents with progressive bilateral swelling of her fingers,
elbows, and toes. Initially thought to represent an inflammatory peripheral
arthropathy, the patient underwent rheumatology review, but subsequent tissue
biopsy confirmed diffuse large B-cell lymphoma. Results of bone marrow biopsy and
staging CT were negative. F-FDG PET/CT demonstrates FDG-avid bony and adjacent
soft tissue disease limited to the extremities with an excellent metabolic
response to primary chemotherapy. This is a rare case of primary bone lymphoma
limited to the extremities mimicking an inflammatory peripheral arthropathy.
PMID- 25140542
TI - CT, MRI, and 18F-FDG PET/CT in a patient with nested stromal epithelial tumor of
the liver.
AB - An 11-year-old girl presented with abnormal weight gain and was found to have
hepatomegaly. MRI of the abdomen revealed a 20-cm hepatic mass. F-FDG PET/CT
showed a large hypermetabolic calcified hepatic mass and couple of mildly
hypermetabolic pulmonary nodules with associated intrathoracic lymphadenopathy.
Liver biopsy was consistent with nested stromal epithelial tumor of the liver, a
rare nonhepatocytic, nonbiliary primary neoplasm of the liver associated with
variable calcification and ossification.
PMID- 25140544
TI - Accidental cannulation of a femoral central venous catheter into the iliolumbar
vein: incidental detection by bone scintigraphy.
AB - Central venous catheterization at the femoral site is associated with higher
complication rates of infections and thrombosis than at the jugular or subclavian
sites. However, the procedure of insertion at the femoral site is considered
safer. We present a unique but dangerous positioning of a left femoral central
venous catheter into the iliolumbar vein. We were aware of this accidental
cannulation by chance when our patient underwent bone scintigraphy. Although a
few cases were reported about accidental cannulation into the ascending lumbar
vein, this is the first case where a femoral central venous catheter was
misplaced into the iliolumbar vein.
PMID- 25140545
TI - Metastatic undifferentiated spindle cell sarcoma of the thyroid gland evaluated
by 18F-FDG PET/CT.
AB - We describe a rare case of metastatic undifferentiated spindle cell sarcoma
(USCS) of the thyroid gland evaluated by 18F-FDG PET/CT. A 63-year-old male
patient with histological diagnosis of USCS of the thyroid gland underwent 18F
FDG PET/CT for staging. PET/CT revealed increased radiopharmaceutical uptake
corresponding to a thyroid mass and mild 18F-FDG uptake in a 7-mm lung nodule,
which was diagnosed as USCS metastasis. Based on these findings, the patient was
referred to surgery and chemotherapy, but he died 6 months later for disease
progression.
PMID- 25140546
TI - FDG PET/CT in evaluation of unusual cutaneous manifestations of breast cancer.
AB - Cutaneous metastases of primary internal malignancies are rare, with an incidence
of 0.7% to 10.4%. Cutaneous manifestations due to breast cancer are the most
common metastases dermatologists observe, with a prevalence of 2.4% and an
incidence of 23.9%. Presence of cutaneous metastases is usually a late event in
disease progression, indicating grave prognosis. Recognition of cutaneous breast
cancer metastases significantly alters therapeutic plans, especially when the
disease was thought to be successfully cured. F-FDG PET CT imaging can detect
cutaneous metastasis and sites of distant metastases and monitor response to
therapy. We report 3 patients with cutaneous-predominant breast carcinoma seen by
FDG PET/CT.
PMID- 25140547
TI - 18F-FDG PET/CT in a case of parasite infection mimicking lung and breast
malignancy.
AB - A 51-year-old woman with dyspnea on exertion, fever, pleural effusion, and
pericardial thickening underwent F-FDG PET/CT, which revealed focal
hypermetabolic lesions in the right lung and left breast. The histopathology of
the lesions was compatible with infiltration of inflammatory cells. Blood
eosinophil counts were elevated, and enzyme-linked immunoassays were positive for
antibodies to several parasites. After antiparasite medication, blood eosinophil
counts were normalized, and PET/CT demonstrated complete disappearance of
abnormal FDG accumulation in the lung and breast.
PMID- 25140548
TI - Focal increased 18F FP-CIT uptake in a recent ischemic lesion in the frontal
lobe.
AB - A 65-year-old male patient was referred for rapid functional decline over 1 month
with dysphagia and dysarthria. Past history disclosed left side weakness for 5
years. F FP-CIT PET/CT was performed to evaluate the possibility of pseudobulbar
palsy. Images showed a defect in the right posterior putamen that was consistent
with an old cerebral infarction lesion. Unexpectedly, an oval area of intense F
FP-CIT uptake was found in the left frontal lobe. MRI and F-FDG PET/CT indicated
the lesion to be caused by recent cerebral ischemia.
PMID- 25140549
TI - Detecting interval metastases and response assessment using 18F-FDG PET/CT after
neoadjuvant chemoradiotherapy for esophageal cancer.
AB - AIM: The aim of this study is to evaluate the potential of FDG PET/CT for the
detection of interval distant metastases after neoadjuvant chemoradiotherapy
(CRT) and the prediction of the pathologic response to CRT in esophageal cancer
patients. PATIENTS AND METHODS: In this retrospective study, all esophageal
cancer patients for whom CRT followed by surgery was planned between January 2008
and April 2013 and in whom an FDG PET/CT was performed before and after CRT were
included. For the response analyses, both FDG PET/CT scans had to be made on a
similar scanner. Metabolic response of the primary tumor was assessed using the
SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). These
parameters were correlated with the pathologic response using the tumor
regression grade (TRG) scale according to Mandard et al (Cancer. 1994;73:2680
2686). RESULTS: In 6 (8%) of 76 consecutively treated patients, new distant
metastases were detected on FDG PET/CT after neoadjuvant CRT; these patients
therefore did not undergo operation. Forty-eight (63%) of 76 patients were
eligible for response analysis. The relative change in SUVmax, MTV, and TLG was
significantly different between patients with a major (TRG, 1-2) and a minor
response (TRG, 3-5) but not between patients with and without a pathologic
complete response. The area under the curve of the receiver operating
characteristic for predicting a major response was 0.70 (95% confidence interval,
0.65-0.92) for a relative decrease in SUVmax, compared with 0.73 (95% confidence
interval, 0.58-0.88) both for MTV and TLG. A relative decrease in SUVmax of 60%
or more had the highest positive predictive value (75%). CONCLUSIONS: Futile
surgery was prevented in 8% of our esophageal cancer patients because interval
metastases were detected on an FDG PET/CT after neoadjuvant CRT. The accuracy for
predicting a complete or major pathologic response was limited and does not
support the use of FDG PET/CT for refraining from surgical treatment.
PMID- 25140550
TI - 18F-FDG PET/CT finding of bilateral primary breast mucosa-associated lymphoid
tissue lymphoma.
AB - Primary breast lymphoma is an extremely rare disease. Primary breast mucosa
associated lymphoid tissue (MALT) lymphoma is even rarer, and bilateral
involvement is exceptional. We report on the F-FDG PET/CT findings in a patient
with primary bilateral breast MALT lymphoma. F-FDG PET/CT showed hypermetabolic
masses in both breasts. The patient was confirmed with bilateral primary breast
MALT lymphoma after total mastectomy. Despite its rarity, primary breast MALT
lymphoma should be considered in patients with hypermetabolic masses in the
breast. If primary breast MALT lymphoma is suspected, F-FDG PET/CT is a useful
tool for initial staging in patients.
PMID- 25140551
TI - Radioiodine uptake in an ovarian mature teratoma detected with SPECT/CT.
AB - A 28-year-old woman underwent a near-total thyroidectomy for papillary carcinoma.
Before radioiodine therapy, the serum thyroid-stimulating hormone level was 50
MUIU/mL, the thyroglobulin level was 1 MUg/L, and the antithyroglobulin was
negative. She received 100 mCi of I for ablation of residual thyroid tissue.
After therapy, I whole-body scan demonstrated focal uptake in the right pelvic
area, which localized to the right ovary on SPECT/CT fusion images. The ovarian
cyst was resected, and histopathological examination revealed a mature teratoma
without thyroid tissue component. At 6-month follow-up, the whole-body
radioiodine scan was normal, and serum thyroglobulin was undetectable.
PMID- 25140552
TI - Whole-body 18F-fluorocholine (FCH) PET/CT and MRI of the spine for monitoring
patients with castration-resistant prostate cancer metastatic to bone: a pilot
study.
AB - INTRODUCTION: Several treatments are proposed for castration-resistant prostate
cancer (CRPC) at the metastatic stage. Monitoring of response using serum
prostate-specific antigen (PSA) levels (sPSA) can be insufficient at this stage.
Imaging has been proposed, in particular, nuclear medicine functional imaging and
MRI, since response of predominant bone metastases is hardly evaluable on CT. Our
aim was to evaluate in patients with CRPC with bone metastases, before and after
various treatment lines, the evolution of sPSA, whole-body 18F-fluorocholine
(FCH) PET/CT and spine MRI (sMRI) that has been proposed for detection of
imminent malignant spinal cord compression. PATIENTS AND METHODS: We
retrospectively gathered a pilot series of 10 patients with CRPC metastatic to
bone who had 47 PSA assays, FCH PET/CT, and spine-MRI (sMRI) performed
concomitantly as routine examinations, before the beginning and at the end of 37
therapeutic intervals (TIs). Blinded reading of FCH PET/CT and sMRI was performed
to evaluate visually whether or not the disease has been progressing (new
lesions, greater size, or greater uptake intensity of known lesions) between the
initial and the final examination of each TI. RESULTS: Visual interpretations
limited to spine FCH (sFCH) PET/CT and sMRI were in accordance for 34 TIs (92%):
14 progressions and 20 nonprogressions. In 2 cases, sFCH did not detect lesions
visible on sMRI: one epiduritis and one 6-mm lesion. In 1 case, MRI missed a
lesion in the sacrum that was detected on sFCH. When whole-body FCH (wbFCH)
PET/CT was taken into account, the agreement with sMRI was limited to 29 TIs
(78%). The 8 discrepant cases were all wbFCH positive and sMRI negative, that is,
a significantly higher frequency of positivity for wbFCH (P < 0.008). Serum PSA
levels increased by more than 25% during 21 TIs, whereas no progression was
visible in 8 TIs on sMRI and in 2 TIs on wbFCH. In 5 TIs, sPSA decreased by more
than 50%, and progression was never detected on imaging. CONCLUSION: In detecting
progression in patients with CRPC metastatic to bone, results of spine imaging
with sMRI and sFCH PET/CT were highly correlated, whereas wbFCH PET/CT showed
significantly more progression statues comparing to sMRI alone related to the
exploration of other parts of the skeleton and of soft tissue.
PMID- 25140553
TI - Clear cell adenocarcinoma of the urethra: 18F-FDG PET/CT imaging.
AB - Clear cell adenocarcinoma of the urethra is a rare and aggressive tumor of female
gender preponderance. This neoplasm, the origin of which is still widely debated,
has been reported with CT and MRI in case reports and small series. To the
previously published conventional cross-sectional imaging description, the
authors add the PET/CT features of this uncommon urologic neoplasm at its
advanced stage in a 60-year-old patient complaining of urinary retention.
PMID- 25140554
TI - A gluten-free vegan meal for gastric emptying scintigraphy: establishment of
reference values and its utilization in the evaluation of diabetic gastroparesis.
AB - PURPOSE: The aim of this study was to describe the preparation of radiolabeled
idli (savory cake) meal for use as an alternate to the egg white sandwich (EWS)
meal in gastric emptying scintigraphy (GES). Furthermore, the aim of this study
was to establish normal emptying rates for this meal and present our experience
in using it in the evaluation of diabetic gastroparesis. PATIENTS AND METHODS:
The meal was prepared using a universally available packaged mix labeled with 1
mCi 99mTc sulfur colloid, and the stability of labeling was tested up to 4 hours
in simulated gastric fluid. One hundred thirteen healthy volunteers (aged 20-78
years; 54 women, 59 men) underwent GES study using the idli meal. Gastric
retention at one-half, 1, 2, and 4 hours after ingestion of the meal was
estimated, and the normal limits were set using the fifth and 95th percentile
values at each period. Having established its normal emptying rates, the idli
meal was further used to evaluate 70 patients suspected with diabetic
gastroparesis. RESULTS: The idli meal, with a calorific value ~282 kcal, has a
relatively higher fat content (8% of total mass) than EWS. More than 96% of 99mTc
sulfur colloid remained bound to the meal after 4 hours suspension in simulated
gastric fluid. Gastric retention greater than 30% and greater than 6% at 2 hours
and 4 hours, respectively, indicated delayed gastric emptying, whereas retention
less than 30% at 1 hour suggested rapid emptying. Among patients suspected with
diabetic gastroparesis, delayed gastric emptying was identified in 76%, and rapid
emptying was seen in 4.2%. CONCLUSIONS: Radiolabeled idli meal is a good
alternative to EWS meal for routine GES, especially among patients with specific
dietary restrictions.
PMID- 25140555
TI - Assessing tumor hypoxia in head and neck cancer by PET with 62Cu-diacetyl-bis(N4
methylthiosemicarbazone).
AB - PURPOSE: The aim of this study was to investigate the potential of PET imaging
with a hypoxia-selective tracer 62Cu-diacetyl-bis(N4-methylthiosemicarbazone)
(62Cu-ATSM) for evaluating the prognosis of patients with head and neck cancer
(HNC). METHODS: Twenty-five patients with HNC including stage II to IV underwent
both 62Cu-ATSM and 18F-FDG PET before the initiation of treatment. Volumes of
interest were placed on the tumor and sternocleidomastoid muscles to obtain
SUVmax and to calculate the tumor-to-muscle activity ratio (TMR). The PET results
were correlated with clinical follow-up, and the receiver operating
characteristic analysis was used to determine the optimal cutoff values.
Progression-free survival (PFS) and cause-specific survival (CSS) were
statistically analyzed. RESULTS: Patients were followed up for periods ranging
from 4 to 32 months. Twelve patients died from local recurrence or metastasis of
a primary cancer, and 2 had recurrence of the 13 remaining patients. Mean (SD)
periods of PFS and CSS were 15.5 (12.5) and 18.6 (11.0) months, respectively.
Optimal cutoff values for each PET index were as follows: SUVs of 62Cu-ATSM
(SUVATSM) and FDG were 3.6 and 7.9; TMRs of ATSM (TMRATSM) and FDG were 3.2 and
5.6. When the cutoff for TMRATSM was set at 3.2, patients with a greater TMRATSM
had significantly worse PFS (P = 0.014) and CSS (P = 0.031). Two-year PFS and CSS
rates were 73% and 80% for patients with a lower TMRATSM (<=3.2); however, they
were 20% and 33% for those with hypoxic tumors (TMRATSM, >3.2), respectively. F
FDG-related indices did not show any significant difference in either PFS or CSS.
CONCLUSIONS: Pretreatment 62Cu-ATSM PET is useful for predicting the prognosis of
patients with HNC.
PMID- 25140556
TI - Nodular fasciitis mimicking soft tissue metastasis on 18F-FDG PET/CT during
surveillance.
AB - Nodular fasciitis (NF) is a common benign soft tissue tumor. However, F-FDG
PET/CT findings of NF are limited. Two cases of NF are described that mimic soft
tissue metastasis on F-FDG PET/CT during surveillance. F-FDG PET/CT is well
documented in the surveillance of malignancy and increasing worldwide. There are
growing chances of encountering FDG-avid nonmalignant soft tissue lesion. Nodular
fasciitis could be considered as possible diagnosis on F-FDG PET/CT if a solitary
well- circumscribed ovoid hypermetabolic soft tissue lesion is located in a
muscle, intermuscular space, or adjacent tendon, especially in patients with a
clinically low probability of tumor recurrence or metastasis.
PMID- 25140557
TI - Detection of osseous metastasis by 18F-NaF/18F-FDG PET/CT versus CT alone.
AB - PURPOSE: Sodium fluoride PET (18F-NaF) has recently reemerged as a valuable
method for detection of osseous metastasis, with recent work highlighting the
potential of coadministered 18F-NaF and 18F-FDG PET/CT in a single combined
imaging examination. We further examined the potential of such combined
examinations by comparing dual tracer 18F-NaF18/F-FDG PET/CT with CT alone for
detection of osseous metastasis. PATIENTS AND METHODS: Seventy-five participants
with biopsy-proven malignancy were consecutively enrolled from a single center
and underwent combined 18F-NaF/18F-FDG PET/CT and diagnostic CT scans. PET/CT as
well as CT only images were reviewed in blinded fashion and compared with the
results of clinical, imaging, or histological follow-up as a truth standard.
RESULTS: Sensitivity of the combined 18F-NaF/18F-FDG PET/CT was higher than that
of CT alone (97.4% vs 66.7%). CT and 18F-NaF/18F-FDG PET/CT were concordant in
73% of studies. Of 20 discordant cases, 18F-NaF/18F-FDG PET/CT was correct in 19
(95%). Three cases were interpreted concordantly but incorrectly, and all 3 were
false positives. A single case of osseous metastasis was detected by CT alone,
but not by 18F-NaF/18F-FDG PET/CT. CONCLUSIONS: Combined 18F-NaF/18F-FDG PET/CT
outperforms CT alone and is highly sensitive and specific for detection of
osseous metastases. The concordantly interpreted false-positive cases demonstrate
the difficulty of distinguishing degenerative from malignant disease, whereas the
single case of metastasis seen on CT but not PET highlights the need for careful
review of CT images in multimodality studies.
PMID- 25140558
TI - 131I abnormal uptake by the thyroid bed from Zuckerkandl tubercle diagnosis by
131I SPECT/CT.
AB - After thyroid remnant ablation following total thyroidectomy for thyroid cancer,
131I SPECT/CT revealed 131I uptake, regarded as thyroid bed uptake on planar
images, in the anterior cervical region. On SPECT/CT, the 131I uptake focus
appeared at the esophagus, suggesting esophageal invasion. No esophageal invasion
had been recognized intraoperatively, and no residual uptake was detected by 131I
scintigraphy evaluating therapeutic effects 3 months after ablation. Preoperative
CT revealed a retrotracheal space portion extending from the normal thyroid with
the same density, suggesting Zuckerkandl tubercle. Abnormal uptake on SPECT/CT
was deemed Zuckerkandl tubercle-derived thyroid bed uptake.
PMID- 25140559
TI - Sister Mary Joseph Nodules on 99mTc HYNIC-TOC scintigraphy in patients with
neuroendocrine tumors.
AB - A Sister Mary Joseph nodule represents an umbilical metastasis, which is more
commonly caused by a primary malignancy in gastrointestinal tract or from
reproductive system. We report Sister Mary Joseph nodules caused by
neuroendocrine tumor and revealed on Tc HYNIC-TOC scintigraphy.
PMID- 25140560
TI - Role of semiquantitative assessment of regional binding potential in 123I-FP-CIT
SPECT for the differentiation of frontotemporal dementia, dementia with Lewy
bodies, and Alzheimer's dementia.
AB - INTRODUCTION: I-FP-CIT SPECT is increasingly used to differentiate between
Alzheimer's dementia (AD) and dementia with Lewy bodies (DLB). The role of I-FP
CIT SPECT in frontotemporal dementia (FTD) is rather unclear, albeit
nigrostriatal involvement may occur. The aim of this study was to evaluate its
role in the differentiation of FTD, DLB, and AD. METHODS: We analyzed 34 patients
with clinical diagnosis of FTD (n = 13), DLB (n = 12), and AD (n = 9) undergoing
combined F-FDG PET and I-FP-CIT SPECT. We performed a semiquantitative region of
interest-based analysis to determine the binding potential values in caudate
nucleus, putamen, and whole striatum including the caudate/putamen binding
potential ratio and asymmetry indices. The receiver operating characteristic
analyses and multinomial logistic regression were conducted to assess
discrimination accuracy. RESULTS: The putaminal binding potential separated DLB
from AD with high accuracy (area under the receiver operating characteristic
curve [AUC], 0.94). It also discriminated FTD from DLB with high accuracy (AUC,
0.92), whereas differentiation between FTD and AD was less accurate (AUC, 0.74).
The binding potential ratio also provided high accuracy for differentiation of
FTD and DLB (AUC, 0.91). Combination of these 2 parameters yielded slightly
higher results for differentiation of FTD and DLB (AUC, 0.97). In a group
including all patients, accuracy remained very high for DLB (AUC, 0.95), whereas
values for FTD (AUC, 0.81) and AD (AUC, 0.80) were lower. CONCLUSIONS:
Semiquantitative assessment of striatal dopamine transporter availability can
differentiate between FTD and DLB as well as DLB and AD with high accuracy,
whereas discrimination between AD and FTD is limited.
PMID- 25140561
TI - Quantitative measurement of blood flow volume in the major intracranial arteries
by using 123i-iodoamphetamine SPECT.
AB - PURPOSE: The aim of this study was to establish the novel automatic method to
quantify blood flow volumes of the major intracranial arteries by using SPECT.
METHODS: We created the vascular templates to cover the territory supplied by the
major intracranial arteries. Each blood flow volume was calculated as the
regional cerebral blood flow on SPECT using this template * volume size of the
template. In this study, we evaluated the volume flows in 22 cerebral hemispheres
with normal perfusion and 28 hemispheres with severe stenosis in the internal
cerebral artery (ICA) or middle cerebral artery (MCA) and that at acetazolamide
test in 16 normal hemispheres and 20 hemispheres with stenosis. RESULTS: The mean
blood flow volumes of the ICA and MCA in the normal hemispheres increased to more
than 40% after acetazolamide test (161-228 mL/min for ICA and 111-157 mL/min for
MCA), although those in the hemispheres with stenosis increased to less than 35%
(158-192 mL/min for ICA and 107-127 mL/min for MCA). The receiver operating
characteristic analyses revealed that the simple difference between the blood
flow volume at acetazolamide test and that at rest using the new MCA template was
superior to detecting reduction of cerebrovascular reactivity (CVR), compared
with the conventional percent CVR using the original template. CONCLUSIONS: Blood
flow volumes of the intracranial arteries had been able to be quantified
automatically on SPECT, and difference of CVR was available for predicting the
blood demand-supply balance.
PMID- 25140562
TI - Clinical benefit of 11C methionine PET imaging as a planning modality for
radiosurgery of previously irradiated recurrent brain metastases.
AB - OBJECT: Stereotactic radiosurgery with gamma knife (GK-SRS) generally improves
the focal control of brain metastases. Yet in cases of focal recurrence at a
previous radiation site, MRI is often imperfect in differentiating between active
tumor and radiation injury. We have examined whether the use of C methionine
(MET) with PET will facilitate this differentiation and improve the outcome of GK
SRS for focally recurrent brain metastases after prior treatment. METHODS: Eighty
eight patients underwent GK-SRS for postirradiation recurrent brain metastases.
Thirty-four patients received radiation in areas manifesting high MET uptake (PET
group) in a dose-planning procedure using MET-PET/MRI fusion images. Fifty-four
patients referred from other institutes received radiation based on dose planning
information obtained from MRI (MRI group). RESULTS: Sex, age, and the ratio of
breast cancer differed significantly between the MRI and PET groups. The total
irradiation volume was significantly smaller in the PET group, and the minimal
irradiation dose was significantly higher. In a multivariable statistical
analysis, the use of MET-PET (P = 0.02) was independently associated with
prolonged overall survival after treatment, Karnofsky performance status (P =
0.002), the number of lesions (P = 0.03), and patient's sex (P = 0.02). The
median survival time was significantly longer in the PET group (18.1 months) than
in the MRI group (8.6 months) (P = 0.01). CONCLUSION: 11C methionine-PET/MRI
fusion images for dose planning lengthened survival in patients undergoing GK-SRS
for focally recurrent brain metastases.
PMID- 25140563
TI - PET response criteria for solid tumors predict survival at three months after
intra-arterial resin-based 90Yttrium radioembolization therapy for unresectable
intrahepatic cholangiocarcinoma.
AB - PURPOSE: PET Response Criteria for Solid Tumors (PERCIST) were assessed and
correlated with survival analysis after resin-based 90Yttrium (90Y)
radioembolization therapy for intrahepatic cholangiocarcinoma (ICC). PATIENTS AND
METHODS: Target and overall PERCIST and Response Criteria for Solid Tumors
(RECIST) treatment responses were assessed in consecutive patients treated with Y
radioembolization for ICC refractory to standard chemotherapy. Significant
measurable tumor was defined as 1 cm or greater in diameter and SUVpeak of 2.5 or
greater in targeted and nontargeted lesions. The PERCIST defines complete
response as resolution of 18F-FDG uptake within measurable lesions, and partial
response as 30% reduction in 18F-FDG peak standardized uptake value in measurable
lesions. Objective response included partial response and complete response.
Survival analysis by Kaplan-Meier and log-rank proportional models was performed
using SPSS software version 20.0 (IBM, Armonk, NY), and significance was set at P
< 0.05. RESULTS: Median overall survival (OS) of 9 consecutive patients (56%
women; mean age, 58 years) from 90Y therapy was 21.7 months. At 3 months, PERCIST
objective response rate of target lesions was 77.7%, and target objective
response on PERCIST correlated significantly to prolonged OS (P = 0.022). Overall
objective PERCIST response at 3 months had significant correlation with OS (P =
0.011). Probability of death was significantly higher in overall nonresponders by
PERCIST (hazard ratio, 12.3). No objective response was seen with RECIST.
CONCLUSIONS: In patients with unresectable ICC refractory to standard
chemotherapy, PERCIST at 3 months for assessment of imaging response after 90Y
radioembolization therapy predict OS.
PMID- 25140564
TI - Stratified radiotracer activity in a floppy neobladder on both 18F-FDG PET/CT and
99mTc-MDP bone scan.
AB - 18F-FDG and 99mTc-MDP are excreted through the renal system. For the most part,
radiotracers are uniformly distributed in the bladder; however, their
distribution can exhibit unique patterns in certain situations. We present a case
of stratified urine activity in a floppy neobladder on nuclear medicine imaging
performed just after CT and MRI contrast studies, respectively.
PMID- 25140565
TI - 11C-PiB PET/CT in nasopharyngeal amyloidosis associated with multiple myeloma.
AB - We present an unusual case of nasopharyngeal amyloidosis associated with multiple
myeloma. A 63-year-old woman presented with 2 months' history of epistaxis and
dentalgia 3 years after being diagnosed with multiple myeloma. CT and C
Pittsburgh compound B (PiB) PET images demonstrated that the intense C-PiB uptake
corresponded to the nasal, paranasal, and palatal area matching the CT mass
lesion. Histopathologic examination confirmed amyloidosis.
PMID- 25140566
TI - Vesicocolic fistula detected by (99m)Tc-MAG3 renogram.
AB - A 55-year-old man presented with 60-lb weight loss in 6 months. An abdominal CT
demonstrated a large mass in the pelvis arising from the sigmoid colon and
invading the urinary bladder. His elevated serum creatinine (1.25 mg/dL)
triggered a request for a Tc-MAG3. Tc-MAG3 renogram demonstrated communication of
the urinary bladder with the descending colon but no evidence of obstruction to
drainage from the kidneys to the bladder. A retrograde cystogram confirmed a
vesicocolic fistula. After multiple rounds of chemotherapy, the patient died 7
months later.
PMID- 25140567
TI - [Until when will Brazil be known as the country of cesarean section?].
PMID- 25140568
TI - [Premature rupture of the membranes before the 35th week: perinatal outcomes].
AB - PURPOSE: To describe the perinatal outcomes after preterm premature rupture of
membranes. METHODS: A retrospective cohort study was carried out at Instituto de
Medicina Integral Prof. Fernando Figueira - IMIP from January 2008 to December
2012. A total of 124 preterm premature rupture of membranes singleton
pregnancies, with gestational age <35, were included in the study. Pregnant women
carrying fetuses with malformations, hypertensive syndromes, diabetes, or
diagnosis of infections at admission were excluded. The pregnant women were
hospitalized for conservative treatment with corticosteroids, antibiotics and
tocolysis with nifedipine if necessary. The results are reported as frequency
distributions and measures of central tendency and dispersion. RESULTS: Seventeen
patients (13.7%) had a gestational age of less than 24 weeks. Mean maternal age
was 25.7 years, mean gestational age at the diagnosis of preterm premature
rupture of membranes was 29 weeks, mean amniotic fluid index was 3.5 cm, and mean
latency period was 10.5 days. Most patients went into spontaneous labor by the
30th week of pregnancy, and the rate of vaginal delivery was 88.2%.
Chorioamnionitis was the most frequent maternal complication (34.7%). Neonatal
sepsis was observed in 12% of patients, and the perinatal mortality rate was
21.5% for the group at or beyond the 24th week of gestation and 76.5% for the
group with less than 24 weeks of gestational age. CONCLUSIONS: A low maternal
mortality rate was observed in preterm premature rupture of membranes; however,
high rates of complications and perinatal death were observed, suggesting that
other conduct protocols should be studied.
PMID- 25140569
TI - [Neonatal mortality and avoidable causes in the micro regions of Sao Paulo
state].
AB - PURPOSE: To identify spatial patterns of neonatal mortality distribution in the
micro regions of Sao Paulo State and verify the role of avoidable causes in the
composition of this health indicator. METHODS: This ecological exploratory study
used neonatal mortality information obtained from Information System and
Information Technology Department of the Brazilian National Healthcare System
(DATASUS) in the period between the years 2007 and 2011. The digital set of micro
regions of Sao Paulo State was obtained from Instituto Brasileiro de Geografia e
Estatistica (IBGE). Moran Indexes were calculated for the neonatal mortality
total rate and rate from avoidable causes; thematic maps were constructed with
these rates, as well as the difference between them; and the Box Map was built.
RESULTS: The overall neonatal mortality rate was 8.42/1,000 live births and
neonatal mortality rate from avoidable causes of 6.19/1,000 live births. Moran
coefficients (I) for these rates were significant (p-value<0.05) - for the total
rate of neonatal mortality I=0.11 and for mortality from preventable causes
I=0.19 -, and neonatal deaths were concentrated in southwest region and the Vale
do Paraiba. If preventable causes were abolished, there would be a significant
reduction in the average rate of overall neonatal mortality, from 8.42 to 2.23
deaths/1,000 live births, representing a decline of 73%. CONCLUSION: This study
demonstrated that neonatal mortality rate would be close to the rates of
developed countries if avoidable causes were abolished.
PMID- 25140570
TI - Relationship between anxiety and overactive bladder syndrome in older women.
AB - PURPOSE: The objective of this study was to investigate the relationship between
overactive bladder syndrome and anxiety in older women. METHODS: Of the 198 older
women who were invited, 29 were excluded and 166 were then divided into two
groups according to the Advanced Questionnaire of Overactive Bladder (OAB-V8):
one group with overactive bladder symptoms (OAB-V8>=8) and the other without the
symptoms of an overactive bladder (OAB-V8<8). The purpose was to conduct a
frequency analysis and to investigate the relation of the social demographic data
and anxiety in the two groups. The Beck Anxiety Inventory (BAI) was used to
evaluate the level of anxiety. The Kolmogorov-Smirnov test was used to determine
the distribution of the data. The differences between the two groups for the
continuous variables were analyzed by the Mann-Whitney U test, the differences
for the categorical variables were analyzed by the Chi-Square test and the
association between the continuous variables was analyzed by the Spearman
Correlation test. The tests were two-tailed with a confidence level of 5%.
RESULTS: Overall, the frequency of an overactive bladder was present in 117
(70.5%) of the participants. The body mass index (BMI) of the group with
overactive bladder symptoms was significantly higher than the BMI of those
without these symptoms (p=0.001). A higher prevalence of mild, moderate and
severe anxiety was observed among older women with overactive bladder symptoms.
In addition, the overactive bladder symptoms group presented a positive low
correlation with anxiety symptoms (r=0.345) and with BMI (r=0.281). There was a
small correlation between BMI and anxiety symptoms (r=0.164). CONCLUSIONS:
Overactive bladder syndrome was prevalent among older women and the existence of
these symptoms was linked to the presence of mild, moderate and/or severe anxiety
symptoms.
PMID- 25140571
TI - [Cross-cultural adaptation of the Pregnancy and Weight Gain Attitude Scale].
AB - PURPOSE: To present the cross-cultural adaptation to Brazilian Portuguese
language of the Pregnancy and Weight Gain Attitude Scale. METHODS: This scale was
developed in order to verify whether attitude toward thinness affects weight gain
during pregnancy and contains statements that express different attitudes of
pregnant women regarding their own weight gain. The procedures were: translation,
back translation, comprehension evaluation, preparation of a final version,
application of the scale to 180 pregnant women (mean age=29.6, gestational
age=25.7 weeks) and psychometric analysis. RESULTS: Satisfactory equivalence
between the versions and satisfactory internal consistency (Cronbach's alpha 0.7)
were detected. The exploratory factor analysis suggested four subscales with
51.4% total variance explained. CONCLUSION: The scale proved to be valid and can
be used in studies with pregnant women in Brazil to assess attitudes toward
weight gain and to detect and prevent dysfunctional behaviors during pregnancy.
PMID- 25140572
TI - [Changes in the extracellular matrix due to diabetes and their impact on urinary
continence].
AB - The prevalence of urinary incontinence in diabetic pregnant women is
significantly high two years after cesarean section. Incontinence can be the most
common consequence of hyperglycemia compared to other complications. Thus,
identifying the risk factors for the development of urinary incontinence in
diabetes is the major aim in the prevention of this very common condition. Recent
surveys have shown that not only muscle but also the urethral extracellular
matrix play an important role in the mechanism of urinary continence.
Translational work on rats by our research group showed that diabetes during
pregnancy damages the extracellular matrix and urethral striated muscle, a fact
that may explain the high prevalence of urinary incontinence and pelvic floor
dysfunction in women with gestational diabetes mellitus. Diabetes affects the
expression, organization and change in extracellular matrix components in
different organs, and tissue remodeling and fibrosis appear to be a direct
consequence of it. Therefore, understanding the impact of modifiable risk
factors, such as diabetes, which involves using preventive strategies, can reduce
the rates of urinary incontinence and the health care costs, and improve the
quality of life of women, especially during pregnancy and postpartum.
PMID- 25140573
TI - Allelic variants at codon 146 in the PRNP gene show significant differences in
the risk for natural scrapie in Cypriot goats.
AB - Previous studies have shown the association between the polymorphisms serine (S)
or aspartic acid (D) at codon 146 of the PRNP gene and resistance to scrapie. All
goats aged >12 months (a total of 1075 animals) from four herds with the highest
prevalence of scrapie in the country were culled and tested, of which 234 (21.7%)
were positive by either the rapid test or immunohistochemistry (IHC) for any of
the tissues tested. The odds of scrapie infection occurring in NN146 goats was
101 [95% credible interval (CrI) 19-2938] times higher than for non-NN146 or
unknown genotypes. IHC applied to lymphoreticular tissue produced the highest
sensitivity (94%, 95% CrI 90-97). The presence of putatively resistant non-NN146
alleles in the Cypriot goat population, severely affected by scrapie, provides a
potential tool to reduce/eradicate scrapie provided that coordinated nationwide
breeding programmes are implemented and maintained over time.
PMID- 25140576
TI - Influence of interfacial rheology on drainage from curved surfaces.
AB - Thin lubrication flows accompanying drainage from curved surfaces surround us
(e.g., the drainage of the tear film on our eyes). These draining aqueous layers
are normally covered with surface-active molecules that render the free surface
viscoelastic. The non-Newtonian character of these surfaces fundamentally alters
the dynamics of drainage. We show that increased film stability during drainage
can occur as a consequence of enhanced surface rheology. Increasing the
surfactant layer viscosity decreases the rate of drainage; however, this
retarding influence is most pronounced when the insoluble surfactant layer has
significant elasticity. We also present a simple theoretical model that offers
qualitative support to our experimental findings.
PMID- 25140577
TI - Clinical significance of 2 h plasma concentrations of first-line anti
tuberculosis drugs: a prospective observational study.
AB - OBJECTIVES: To study 2 h plasma concentrations of the first-line tuberculosis
drugs isoniazid, rifampicin, ethambutol and pyrazinamide in a cohort of patients
with tuberculosis in Denmark and to determine the relationship between the
concentrations and the clinical outcome. METHODS: After 6-207 days of treatment
(median 34 days) 2 h blood samples were collected from 32 patients with active
tuberculosis and from three patients receiving prophylactic treatment. Plasma
concentrations were determined using LC-MS/MS. Normal ranges were obtained from
the literature. Clinical charts were reviewed for baseline characteristics and
clinical status at 2, 4 and 6 months after the initiation of treatment. At a 1
year follow-up, therapy failure was defined as death or a relapse of
tuberculosis. RESULTS: Plasma concentrations below the normal ranges were
frequently observed: isoniazid in 71%, rifampicin in 58%, ethambutol in 46%,
pyrazinamide in 10% and both isoniazid and rifampicin in 45% of the patients. The
plasma concentrations of isoniazid correlated inversely with the C-reactive
protein level at the time of sampling (P = 0.001). During 1 year of follow-up,
therapy failure occurred in five patients. Therapy failure occurred more
frequently when the concentrations of isoniazid and rifampicin were both below
the normal ranges (P = 0.013) and even more frequently when they were below the
median 2 h drug concentrations obtained in the study (P = 0.005). CONCLUSIONS: At
2 h, plasma concentrations of isoniazid and rifampicin below the normal ranges
were frequently observed. The inverse correlation between the plasma
concentrations of isoniazid and C-reactive protein indicate a suboptimal
treatment effect at standard dosing regimens. Dichotomization based on median 2 h
drug concentrations was more predictive of outcome than dichotomization based on
normal ranges.
PMID- 25140578
TI - Molecular surveillance and prevalence of carbapenem-resistant Enterobacteriaceae
in Northern Taiwan.
PMID- 25140579
TI - Molecular basis of non-mutational derepression of ramA in Klebsiella pneumoniae.
AB - OBJECTIVES: The ram locus, consisting of the romA-ramA genes, is repressed by the
tetracycline-type regulator RamR, where regulation is abolished due to loss-of
function mutations within the protein or ligand interactions. The aim of this
study was to determine whether the phenothiazines (chlorpromazine and
thioridazine) directly interact with RamR to derepress ramA expression. METHODS:
Quantitative real-time PCR analyses were performed to determine expression levels
of the romA-ramA genes after exposure to the phenothiazines. Electrophoretic
mobility shift assays (EMSAs) and in vitro transcription experiments were
performed to show direct binding to and repression by RamR. Direct binding of the
RamR protein to the phenothiazines was measured by fluorescence spectroscopy
experiments and molecular docking models were generated using the RamR crystal
structure. RESULTS: Exposure to either chlorpromazine or thioridazine resulted in
the up-regulation of the romA-ramA genes. EMSAs and in vitro transcription
experiments demonstrated that both agents reduce/abolish binding and enhance
transcription of the target PI promoter upstream of the ramR-romA genes in
Klebsiella pneumoniae compared with RamR alone. Fluorescence spectroscopy
measurements demonstrated that RamR directly binds both chlorpromazine and
thioridazine with micromolar affinity. Molecular docking analyses using the RamR
crystal structure demonstrated that the phenothiazines interact with RamR protein
through contacts described for other ligands, in addition to forming unique
strong polar interactions at positions D152 and K63. CONCLUSIONS: These data
demonstrate that phenothiazines can modulate loci linked to the microbe-drug
response where RamR is an intracellular target for the phenothiazines, thus
resulting in a transient non-mutational derepression of ramA concentrations.
PMID- 25140580
TI - Premenstrual syndrome in Turkish medical students and their quality of life.
AB - This study aimed to analyse the frequency and symptoms of premenstrual syndrome
(PMS) and its effect on quality of life in medical students. Sociodemographic
data, a symptom calendar for the following consecutive two menstrual periods and
SF-36 quality of life questionnaire were collected. A total of 228 students
joined the survey. The average age of the students was 20.77 +/- 1.90. The
frequency of PMS was 91.8%. The most frequent symptoms were abdominal bloating
(89.5%), irritability (88.3%) and breast tenderness (82.6%). Quality of life
scores ranged from 17.00 to 97.00 and were lowest in the severe PMS group.
Alcohol consumption, stress events and fat rich diets increased the severity of
PMS. Family history significantly affected the severity of PMS and quality of
life scores. Premenstrual syndrome was found to be a frequent entity among
medical students and seemed to affect quality of life in a moderate way.
PMID- 25140581
TI - The interprofessional clinical experience: interprofessional education in the
nursing home.
AB - The interprofessional clinical experience (ICE) was designed to introduce
trainees to the roles of different healthcare professionals, provide an
opportunity to participate in an interprofessional team, and familiarize trainees
with caring for older adults in the nursing home setting. Healthcare trainees
from seven professions (dentistry, medicine, nursing, nutrition, occupational
therapy, optometry and social work) participated in ICE. This program consisted
of individual patient interviews followed by a team meeting to develop a
comprehensive care plan. To evaluate the impact of ICE on attitudinal change, the
UCLA Geriatric Attitudes Scale and a post-experience assessment were used. The
post-experience assessment evaluated the trainees' perception of potential team
members' roles and attitudes about interprofessional team care of the older
adult. Attitudes toward interprofessional teamwork and the older adult were
generally positive. ICE is a novel program that allows trainees across healthcare
professions to experience interprofessional teamwork in the nursing home setting.
PMID- 25140583
TI - Herpes Simplex Keratitis in Rheumatoid Arthritis Patients.
AB - PURPOSE: To describe a series of 5 patients with herpes simplex virus keratitis
(HSK) and rheumatoid arthritis (RA) under immunosuppressive treatment. METHODS:
Retrospective study. Detailed data were obtained regarding symptoms and signs at
the initial evaluation, treatment, microbiological diagnostic tests, evolution,
and outcomes. RESULTS: Five patients with HSK and RA were identified. Bilateral
involvement occurred in 2 patients (40%). Epithelial keratitis was diagnosed in 5
eyes. Three eyes showed severe melting with eye perforation. Gram-positive
bacterial co-infections were common in the group with stromal keratitis. We did
not find differences in the evolution of the disease based on anti-rheumatoid
treatment. CONCLUSIONS: The characteristics of HSK in patients with RA differed
from HSK in immunocompetent patients. The stromal keratitis cases were very
aggressive and difficult to manage, with perforation and gram-positive bacterial
co-infection as frequently associated conditions. Prophylactic therapy at
standard doses was unsuccessful to avoid recurrences.
PMID- 25140582
TI - Reemergence of hedgehog mediates epithelial-mesenchymal crosstalk in pulmonary
fibrosis.
AB - Hedgehog signaling plays important roles in cell development and differentiation.
In this study, the ability of Sonic Hedgehog (SHH) to induce myofibroblast
differentiation was analyzed in isolated human lung fibroblasts, and its in vivo
significance was evaluated in rodent bleomycin-induced pulmonary fibrosis. The
results showed that SHH could induce myofibroblast differentiation in human lung
fibroblasts in a Smo- and Gli1-dependent manner. Gel shift analysis, chromatin
immunoprecipitation assay, and site-directed mutagenesis revealed that a Gli1
binding consensus in the alpha-SMA gene promoter was important for mediating SHH
induced myofibroblast differentiation. Analysis of Hedgehog reemergence in vivo
revealed that of all three Hedgehog isoforms, only SHH was significantly induced
in bleomycin-injured lung along with Gli1. The induction of SHH was only noted in
epithelial cells, and its expression was undetectable in lung fibroblasts or
macrophages. transforming growth factor (TGF)-beta induced SHH significantly in
cultured alveolar epithelial cells, whereas SHH induced TGF-beta in lung
fibroblasts. Pulmonary fibrosis and alpha-smooth muscle actin (alpha-SMA)
expression were significantly reduced in mice that were Smo deficient only in
type I collagen-expressing cells. Thus, the reemergence of SHH in epithelial
cells could result in induction of myofibroblast differentiation in a Smo
dependent manner and subsequent Gli1 activation of the alpha-SMA promoter.
PMID- 25140584
TI - The effect of prasugrel on ADP-stimulated markers of platelet activation in
patients with sickle cell disease.
AB - Platelets of patients with sickle cell disease (SCD) show evidence of mild
activation in the non-crisis steady state and greater activation during vaso
occlusive crises (VOC). Prasugrel, a potent inhibitor of ADP-mediated platelet
activation and aggregation, may be useful in attenuating VOC. We compared
platelet responses to ADP stimulation in patients with SCD and healthy subjects
before and after treatment with prasugrel. In a phase 1 study, platelet biomarker
levels were assessed in 12 adult patients with SCD and 13 healthy subjects before
and after 12 +/- 2 days of 5.0 or 7.5 mg/day prasugrel. The following were
determined in whole blood samples stimulated with 20 uM ADP: (i) percentages of
monocytes and neutrophils with adherent platelets (cell-platelet aggregates);
(ii) the relative number (mass) of platelets associated with each monocyte and
neutrophil as reported by CD61 mean fluorescence intensity (MFI) of the monocyte
platelet and neutrophil-platelet aggregates; (iii) the percentages of platelets
positive for surface expression of CD40 ligand (CD40L), P-selectin (CD62p) and
activated glycoprotein IIb-IIIa (GPIIb-IIIa); and (iv) the percentages of
platelets and monocyte-platelet aggregates positive for surface tissue factor
(TF) expression. At baseline, there were no significant differences between
cohorts in the percentages of platelets expressing activation biomarkers.
Following 12 days of prasugrel administration, the percentages of platelets
expressing activation biomarkers following ADP stimulation were reduced in both
cohorts, and there were no significant differences between groups. Both patients
with SCD and healthy subjects had significant reductions in the monocyte-platelet
and neutrophil-platelet aggregate MFI and the percentage of platelets expressing
P-selectin and activated GPIIb-IIIa (all p < 0.05). Healthy subjects also had
significant reductions in monocyte-platelet aggregate percentages (p = 0.004),
neutrophil-platelet aggregate percentages (p = 0.011) and the percentage of CD40L
positive platelets (p = 0.044) that were not observed in patients with SCD.
Prasugrel administration to SCD patients attenuates ex vivo ADP-stimulated
platelet activation as measured by the percentage of platelets positive for P
selectin and GPIIb-IIIa, thus reducing the proportion of platelets that may
participate in aggregates. Furthermore, prasugrel decreases ex vivo ADP
stimulated platelet aggregation with monocytes and neutrophils as measured by the
monocyte-platelet and neutrophil-platelet aggregate MFI. This implies that in the
presence of prasugrel, fewer platelets adhere to monocytes and neutrophils, which
may result in reducing cell-platelet aggregate size. Therefore, reduced platelet
reactivity and decreased size of leukocyte-platelet aggregates suggest additional
mechanisms by which prasugrel may provide benefit to patients with SCD and
support further investigation of possible therapeutic benefits of prasugrel in
this population.
PMID- 25140585
TI - Add-on deep transcranial magnetic stimulation (dTMS) in patients with dysthymic
disorder comorbid with alcohol use disorder: a comparison with standard
treatment.
AB - OBJECTIVES: Dorsolateral prefrontal cortex (DLPFC) is dysfunctional in mood and
substance use disorders. We predicted higher efficacy for add-on bilateral
prefrontal high-frequency deep transcranial magnetic stimulation (dTMS), compared
with standard drug treatment (SDT) in patients with dysthymic disorder
(DD)/alcohol use disorder (AUD) comorbidity. METHODS: We carried-out a 6-month
open-label study involving 20 abstinent patients with DSM-IV-TR AUD comorbid with
previously developed DD. Ten patients received SDT for AUD with add-on bilateral
dTMS (dTMS-AO) over the DLPFC, while another 10 received SDT alone. We rated
alcohol craving with the Obsessive Compulsive Drinking Scale (OCDS), depression
with the Hamilton Depression Rating Scale (HDRS), clinical status with the
Clinical Global Impressions scale (CGI), and global functioning with the Global
Assessment of Functioning (GAF). RESULTS: At the end of the 20-session dTMS
period (or an equivalent period in the SDT group), craving scores and depressive
symptoms in the dTMS-AO group dropped significantly more than in the SDT group (P
< 0.001 and P < 0.02, respectively). CONCLUSIONS: High frequency bilateral DLPFC
dTMS with left preference was well tolerated and found to be effective as add-on
in AUD. The potential of dTMS for reducing craving in substance use disorder
patients deserves to be further investigated.
PMID- 25140586
TI - Impact of lifetime psychiatric diagnosis on long-term retention and survival of
former opiate addicts in methadone maintenance treatment.
AB - OBJECTIVES: To characterize lifetime psychiatric diagnosis groups among methadone
maintenance treatment (MMT) patients and associations of diagnosis to long-term
(up to 20 years) retention and survival either during treatment or post
discontinuation. METHODS: A total of 758 patients with available psychiatric
diagnosis (98% of those ever admitted between June 1993 and June 2012) were
followed-up until June 2013. Lifetime psychiatric diagnosis was assessed
according to DSM-IV-TR (Axis I, II, I & II, or none). Observed urine samples at 1
and 13 months were positive for drugs if at least one was positive. Survival data
were based on the Israel National Population Registry. Survival and retention in
MMT were compared (Kaplan Meier) between groups. RESULTS: The Axis II
(personality disorders) group had the worst mean long-term retention (5.8 years,
95% Confidence Interval (CI) 5.0-6.5) compared with the Axis I, Axis I & II or no
psychiatric diagnosis groups (9.6 years, 95% CI 8.8-10.4) (P < 0.0005). Mean
survival since admission (16.4 years, 95% CI 15.9-16.9) was similar for all
groups. Axis II patients included more males, more drug injectors, were younger
at initial opiate use and more likely left treatment before 1 year. CONCLUSIONS:
Personality and coping mechanisms (Axis II) could be significant obstacles to the
success of MMT, warranting special interventions to overcome them.
PMID- 25140588
TI - Isolation and characterization of mesenchymal progenitors derived from the bone
marrow of goats native from northeastern Brazil.
AB - PURPOSE: To characterize bone marrow progenitors cells grown in vitro, using
native goats from northeastern Brazil as animal model. METHODS: Ten northeastern
Brazil native goats of both genders were used from the Piaui Federal University
Agricultural Science Center's (UFPI) - Goat Farming Sector. Bone marrow aspirates
where taken from the tibial ridge and seeded on culture plates for isolation,
expansion and Flow Cytometry (expression markers - Oct-3/4, PCNA, Ck-Pan,
Vimentina, Nanog). RESULTS: Progenitor cells showed colonies characterized by the
presence of cell pellets with fibroblastoid morphology. Cell confluence was taken
after 14 days culture and the non-adherent mononuclear cell progressive
reduction. After the first passage, 94.36% cell viability was observed, starting
from 4.6 x 106 cell/mL initially seeded. Cells that went through flow cytometry
showed positive expression for Oct-3/4, PCNA, Ck-Pan, Vimentina, and Nanog.
CONCLUSIONS: Bone marrow progenitor isolated of native goats from northeastern
Brazil showed expression markers also seen in embryonic stem cells (Oct-3/4,
Nanog), markers of cell proliferation (PCNA) and markers for mesenchymal cells
(Vimentina and Ck-pan), which associated to morphological and culture growth
features, suggest the existence of a mesenchymal stem cell (MSC) population in
the goat bone marrow stromal cells studied.
PMID- 25140587
TI - Effect of a brief seated massage on nursing student attitudes toward touch for
comfort care.
AB - BACKGROUND: While massage has been removed from nursing curricula, studies have
reported massage as safe and effective for stress reduction, relaxation, pain
relief, fatigue, and quality of life. OBJECTIVE: To compare the efficacy of two
intensities of touch administered during two seated massages on the attitudes of
nursing students toward touch for their self-care and patient care. PARTICIPANTS:
Nursing students who volunteered gave institutional review board-approved written
informed consent to undergo massage by a licensed massage therapist.
SETTINGS/LOCATION: A private room adjacent to the nursing lab in a school of
nursing. INTERVENTION: Brief seated massages of differing intensities. Each
participant received low-intensity and high-intensity touch in a two-block,
randomized order, within-subjects design. Linear mixed models nested within
subject and random intercept analyses were used to test hypotheses in this two
treatment, two-sequence, two-period crossover design. OUTCOME MEASURES: Health
questionnaires/visual analogue scales pertaining to physical/affective/and
attitudinal status were completed before and after each massage. RESULTS: Twenty
nine participants (93% female, 83% single) completed the study. Before massage,
the optimal intensity of touch anticipated for self-comfort was 6.6 (0=no
pressure;10=most intense pressure imaginable). The mean touch intensities were
6.7 for high-intensity massage and 0.5 for low-intensity (p<0.001). The overall
percentage differences (feeling better or worse) following massage were as
follows: low intensity, 37.5% better; high intensity, 62.7% better (p<0.001).
Significantly more improvement was reported for energy, pain, stress, and feeling
physically uptight after high-intensity compared with low-intensity (p<0.03).
Participants were more likely to both receive touch for self-care and provide
touch for patient care after experiencing high- versus low-intensity massage
(p<0.01). CONCLUSIONS: High-intensity seated massage was more efficacious than
low-intensity massage and positively influenced nursing student attitudes toward
the inclusion of massage in self-care/patient care. The role of touch for self
care/patient care in the nursing curricula merits reconsideration.
PMID- 25140589
TI - Light-emitting diode effects on combined decellularization of tracheae. A novel
approach to obtain biological scaffolds.
AB - PURPOSE: To obtain a decellularized tracheal scaffold associating traditional
approaches with the novel light-emitting diode (LED) proposal. METHODS: This
study was performed with New Zealand adult rabbits weighing 3.0 - 4.0 kg.
Different protocols (22) were used combining physical (agitation and LED
irradiation), chemical (SDS and Triton X-100 detergents), and enzymatic methods
(DNase and RNase). RESULTS: Generally, the cells surrounding soft tissues were
successfully removed, but none protocol removed cells from the tracheal
cartilage. However, longer protocols were more effective. The cost-benefits
relation of the enzymatic processes was not favorable. It was possible to find
out that the cartilaginous tissue submitted to the irradiation with LED 630nm and
475 nm showed an increased number of gaps without cells, but several cells were
observed to be still present. CONCLUSION: The light-emitting diode is a promising
tool for decellularization of soft tissues.
PMID- 25140590
TI - The establishment and evaluation of rabbit model for peripherally inserted
central catheter.
AB - PURPOSE: To establish a model to simulate the clinical specific process of
peripherally inserted central catheter (PICC) on rabbits, and detect how long the
catheter can be indwelled. METHODS: Seventeen healthy New Zealand white rabbits
were inserted the PICC according to the clinical specific procedure. With the
principle of random, the rabbits were divided into four groups (14d, 21d, 28d,
35d). Each group contains four rabbits, and Group 1 was served as blank control
group. When finishing the experiment, we took the blood vessels which was
inserted the catheter and observed the changes of vascular endothelium using the
Hematoxylin-Eosin (HE) staining. RESULTS: 90% animals were succeeded in inserting
PICC. Early signs of endovascular inflammation were predominantly neutrophils,
then mainly monocytes, visible fibrous tissue hyperplasia of the vessel wall,
vascular endothelial proliferation and granuloma formation. And after that the
irreversible changes in the blood vessels could be observed, especially five
weeks after catheterization. CONCLUSIONS: We have succeeded in establishing the
rabbit model for peripherally inserted central catheter, and provided a new way
for nursing teaching and training. Since the irreversible changes of the vascular
endothelium, it is recommended that the time of indwelling is not more than five
weeks on animal.
PMID- 25140591
TI - Effects of traction on the spermatic cord of rats.
AB - PURPOSE: To determine whether tension in the spermatic cord of rats causes
lesions in the testis, epididymis or vas deferens. METHODS: Forty Wistar rats
were randomly allocated into four groups. A traction force of 1.6 Newton (N) in
group I and 1 N in group II was applied to the right spermatic cord. Group III
was the sham, and group IV served as the control. RESULTS: Testicular lesions
occurred on the right side in 66.7% of the rats and on the left side in 46.1% of
the rats. The testes showed a decreased number of Sertoli cells, necrosis and a
decreased number of germ cells in the seminiferous tubules. Anatomopathological
changes in the vas deferens were not identified. There was no decrease in the
thickness of the muscle wall of the vas deferens. In the right epididymis, 71.8%
of the animals showed a reduction and 5% showed an absence of intraluminal sperm.
In the left epididymis, 37.5% of the rats showed a reduction. The volume and the
final testicular weight of the right side in group IV was different from those in
the other groups. CONCLUSIONS: Anatomopathological lesions were found in the
testis and epididymis.
PMID- 25140592
TI - Analysis of the histology of the scar bladder and biochemical parameters of rats
with a solitary kidney undergoing immunosuppression with tacrolimus.
AB - PURPOSE: To evaluate bladder histology in healing and biochemical analysis of
rats with single kidney in ischemia/reperfusion, treated with tacrolimus.
METHODS: Fifty rats randomized into five groups. Three rats died in surgery, 47
rats divided in groups: Control (non-operated, n=10), Sham (operated without
drugs, n=8), T1 (operated + tacrolimus 1mg/kg, n=10), T2 (operated + tacrolimus
0.1 mg/kg, n=10), T3 (operated + tacrolimus 10mg/kg, n=9). The surgery was:
laparotomy, right nephrectomy, left kidney ischemia/reperfusion, cystotomy
followed by bladder suture. After that, rats were submited to gavage daily
(Control and Sham with saline solution. T1, T2, T3 with tacrolimus in doses
already mentioned). On the 14th day, after death induction, cystectomy was
performed and bladder was histologicaly analysed. The serum urea, creatinine and
tacrolimus were analysed too. RESULTS: There was difference in serum tacrolimus
in T3 compared to the other groups (p<0.05). There was higher doses of creatinine
in T3 group and higher urea in groups with tacrolimus. There were significant
differences among all histologic variables comparing groups with and without
tacrolimus (p<0.05). CONCLUSION: Tacrolimus associated with ischemia/reperfusion
is nephrotoxic, suppresses inflammation and seems to delay the healing bladder.
PMID- 25140593
TI - Effect of allopurinol on the kidney function, histology and injury biomarker
(NGAL, IL 18) levels in uninephrectomised rats subjected to ischaemia-reperfusion
injury.
AB - PURPOSE: To investigate whether allopurinol exerts a protective effect on kidneys
by measuring new kidney injury biomarkers (NGALp, NGALu, KIM 1 and IL 18) and
analysing the renal function and histology in uninephrectomised rats subjected to
ischaemia-reperfusion injury. METHODS: Thirty two Wistar rats were randomly
allocated to four groups: Sham (S): laparotomy; Control (C): laparotomy and
ischaemia-reperfusion in the left kidney; Control Allopurinol (CA): laparotomy
and allopurinol at a dose of 100mg.kg 1.d 1; and Allopurinol (A): laparotomy
ischaemia-reperfusion in the left kidney and allopurinol at a dose of 100mg.kg
1.d 1. The NGALp, NGALu, KIM 1, IL 18 and creatinine levels and the kidney
histology were analysed. The significance level was established as p<0.05.
RESULTS: Creatinine level increased in all the groups, with A ~ C > S ~ CA. The
NGALp, NGALu and IL 18 levels exhibited similar behaviour in all the groups. KIM
1 was higher in group A than C and showed intermediate values in groups S and CA.
Severity of injury in the left kidney was greater in groups C and A compared to S
and CA. CONCLUSION: Allopurinol did not exert protective or damaging effects on
the kidneys of rats subjected to ischaemia-reperfusion injury.
PMID- 25140594
TI - Effect of vitamin K1 supplementation on left colon healing in rats with
extrahepatic biliary obstruction.
AB - PURPOSE: To evaluate the effects of vitamin K1 on wound healing in the left colon
of rats with experimental biliary obstruction. METHODS: Sixteen male rats,
divided into four groups of four animals each (L, M, LK, and MK), underwent
colostomy followed by bowel suture in the left colon. Seven days before, animals
in the L and LK groups had undergone common bile duct ligation. The animals in
groups MK and LK received vitamin K1 supplementation. On day 7 after bowel
suture, repeat laparotomy was performed for evaluation of colonic healing by
burst pressure measurement and collection of samples for histopathological
analysis. Changes in body weight were evaluated in the four groups. RESULTS:
Weight loss was lower in animals supplemented with vitamin K. No significant
differences were observed in burst pressure among the four groups (p>0.05).
Histological analysis showed more hemorrhage and congestion in the biliary
obstruction groups. Supplemented animals exhibited increased collagen formation
and less edema and abscess formation. CONCLUSION: Vitamin K supplementation
attenuated weight loss and improved colonic wound healing in rats.
PMID- 25140595
TI - Copaiba oil effect under different pathways in mice subjected to sepsis.
AB - PURPOSE: To evaluate the effects of copaiba oil administered by different routes
on survival of mices subjected to cecal ligation and puncture. METHODS: Thirty
two mice were distributed into four study groups (N=8): Sham group: normal
standard animals; CONTROL GROUP: submitted a cecal ligation and puncture (CLP);
Gavage group: submitted a CLP, and treat with copaiba oil by gavage; and
Subcutaneous group: submitted a CLP, and treat with copaiba oil by subcutaneous
injection. After the death of the histological analysis were performed. The
Kaplan-Meier curves of surviving time were realized. RESULTS: All animals that
received copaiba, regardless of the route used, survived longer when compared to
the control group (p<0.0001), whereas the survival time ranged from 20 hours for
the control group up to 32 hours for the animals of gavage group and 52 for
subcutaneous group. The animals that received gavage copaiba lived about and
about 20 hours unless the subcutaneous group (p=0.0042). There was no statistical
difference when compared the intensity of inflammatory response (p>0.05)
CONCLUSION: Prophylactic subcutaneous administration of copaiba in mice subjected
to severe sepsis by cecal ligation and puncture, resulted in a survival time
higher than non-use or use of this oil by gavage.
PMID- 25140596
TI - Face transplantation in rats. Reproducibility of the experimental model in
Brazil.
AB - PURPOSE: To investigate the reproducibility of the experimental model of face
allotransplantation in rats in Brazil. METHODS: Eighteen rats were operated, nine
nine donors recipients. Animals underwent transplantation of the left hemiface,
with periorbital and scalp. Transplants were made from donor Wistar rats to
recipients Lewis rats. Flaps were based on the common carotid artery and the
external jugular vein of the donor animal and the anastomosis in the recipient
area was performed in common carotid artery (end-to-side) and in external jugular
vein (end-to-end). RESULTS: Of the nine recipient animals operated, six survived
and three progressed to death in the first days after surgery (survival rate =
67%). The mean time of the procedure was 252 minutes and the mean time of flap
ischemia was 95 minutes. The five surviving animals were sacrificed at 14 days,
in good general condition and without signs of tissue rejection. CONCLUSIONS: The
experimental model of face allotransplantation in rats is reproducible in our
midst. Duration of surgery, time of flap ischemia, animal survival rate and
complications observed were similar to those described in the literature.
PMID- 25140597
TI - Nutraceutical preconditioning with arginine and oil mixes. Effects on
inflammatory mediators, oxidative stress and lipid profile in patients undergoing
radical prostatectomy.
AB - PURPOSE: To investigate whether there is any effect resulting from
preconditioning with nutraceutical supplementation containing arginine and oil
mixes with high omega9:omega6 ratio and low omega6:omega3 ratio containing EPA
and DHA, ALA fatty acids on inflammatory mediators, antioxidant and lipid profile
modulation in surgical trauma. METHODS: Twenty-six men scheduled for radical
prostatectomy were randomized into three groups and treated as follows: Group 1
(skim milk, 0% fat), Group 2 (supplement with omega6:omega3 ratio of 8:1 and
arginine) and Group 3 (supplement with high omega9:omega6 ratio of 3.2:1 and low
omega6:omega3 ratio of 1.4:1 and arginine). Patients received skin milk or
supplements twice a day (200 ml) during five days prior to surgery. Peripheral
venous blood samples were collected at three different timepoints: five days
before surgery (PRE), before anesthesia induction (IND) and on the 2nd
postoperative day (POS). Parameters analyzed included inflammatory cytokines (IL
1beta, IL-6, IL-8 and TNF-alpha), antioxidants (catalase), lipid profile and heat
shock protein (HSP-27). RESULTS: There were no significant differences between
groups on inflammatory mediators and antioxidant parameters. However, lipid
profile values (Cholesterol, LDL, Triglycerides, VLDL), were significantly
different. CONCLUSION: Preconditioning with arginine and oil mixes containing
high omega9:omega6 ratio and low omega6:omega3 ratio, has no effects on
inflammatory mediators and oxidative stress in patients undergoing radical
prostatectomy. Reduction of cholesterol, triglycerides, LDL and VLDL profiles may
be related to the trauma effect.
PMID- 25140598
TI - Zero prevalence of vancomycin-resistant enterococci among Swedish preschool
children.
AB - OBJECTIVES: Enterococci are a natural part of the bacterial flora of humans,
animals, and insects and are frequently found in the community. Vancomycin
resistant enterococci (VRE) have emerged as a growing problem, associated with
high morbidity and mortality. The aim of this study was to investigate the
prevalence of VRE among healthy Swedish preschool children and ascertain whether
they constitute a reservoir for the bacteria. METHODS: In total, 313 individual
diapers were collected from preschools in Uppsala, Sweden. Fecal samples were
screened by analyzing the color change in a broth followed by polymerase chain
reaction for vanA and vanB genes, which are associated with vancomycin
resistance. RESULTS: Neither vanA nor vanB genes could be detected from the
samples. CONCLUSIONS: Preschool children in Uppsala do not constitute a reservoir
for VRE. The zero prevalence is consistent with the overall decline in VRE
prevalence in Sweden during the last years.
PMID- 25140600
TI - Modelling and control of cholera on networks with a common water source.
AB - A mathematical model is formulated for the transmission and spread of cholera in
a heterogeneous host population that consists of several patches of homogeneous
host populations sharing a common water source. The basic reproduction number R0
is derived and shown to determine whether or not cholera dies out. Explicit
formulas are derived for target/type reproduction numbers that measure the
control strategies required to eradicate cholera from all patches.
PMID- 25140599
TI - Deferoxamine but not dexrazoxane alleviates liver injury induced by endotoxemia
in rats.
AB - The purpose of the present study was to compare the activity of two different
clinically available iron chelators on the development of acute liver injury
after administration of the bacterial endotoxin (lipopolysaccharide [LPS]) in
rats. Lipopolysaccharide was administered either alone or after pretreatment with
dexrazoxane (DEX) or deferoxamine (DFO). Control groups received only saline or
its combination with either chelator. After 8 h, untreated LPS rats developed
liver injury, with signs of inflammation and oxidative stress. Lipopolysaccharide
reduced plasma iron concentrations in association with increased production of
hepcidin and the reduced liver expression of ferroportin. Administration of
chelating agents to LPS animals showed distinct effects. Although both drugs were
able to reduce liver iron content, together with corresponding changes in
hepcidin and ferroportin expressions, only DFO showed a protective effect against
liver injury despite relatively small liver concentrations. In sharp contrast,
DEX failed to improve any hallmark of liver injury and even worsened the GSH/GSSG
ratio, the indicator of oxidative stress in the tissue. High-performance liquid
chromatography-mass spectrometry analysis showed marked liver accumulation of
iron-chelating metabolite of DEX (ADR-925), whereas the parent compound was
undetectable. Further downregulation of transporters involved in bile formation
was observed after DFO in the LPS group as well as in healthy animals. Neither
chelator imposed significant liver injury in healthy animals. In conclusion, we
demonstrated marked differences in the modulation of endotoxemic liver impairment
between two iron chelators, implicating that particular qualities of chelating
agents may be of crucial importance.
PMID- 25140601
TI - Validation of a French (Quebec) version of the Tinnitus Handicap Inventory.
AB - OBJECTIVE: To assess the psychometric properties of the Quebec French translation
of the Tinnitus Handicap Inventory (THI-FQ). DESIGN: The original version of the
THI was translated into French by two different people, and then revised before
being administered to 221 study participants. A subgroup of 75 participants also
completed the French versions of the Beck Depression Inventory II (BDI-II) and
the Tinnitus Reaction Questionnaire (TRQ). STUDY SAMPLE: The study participants
used French as their home language, had completed an otolaryngology (ENT)
assessment, and had sought help with disabling tinnitus. RESULTS: No differences
were found according to gender, age, or degree of hearing loss. The THI-FQ was
very stable over a period of approximately 32 days. Internal consistency was 0.93
for the total score. Convergent validity with the TRQ was 0.81 (p < 0.001) while
construct validity, as obtained with the BDI-II, was 0.74 (p < 0.001). As in
other studies, the factor analysis did not confirm the structure proposed by
Newman et al in the original study (1996). CONCLUSIONS: The THI-FQ presents very
good reliability and validity, comparable to translations in other languages and
the original version.
PMID- 25140602
TI - Investigation of a matrix sentence test in noise: reproducibility and
discrimination function in cochlear implant patients.
AB - OBJECTIVE: The aim of this study was to describe common properties
(reproducibility, discrimination function, and its steepness) of matrix tests
used for cochlear implant (CI) users and to obtain data for the German-language
version matrix test, the Oldenburg sentence test (OLSA), presented in noise.
DESIGN: The speech reception thresholds (SRT) in noise were measured by means of
an adaptive test procedure, and by measurement at various signal-to-noise ratios
to determine the course of the entire discrimination function per subject. STUDY
SAMPLE: The measurements were performed on 38 CI users fitted with a Cochlear(TM)
Freedom((r)) or a Cochlear(TM) Nucleus((r)) 5 CI system. RESULTS: The test-retest
reproducibility showed a significant dependence on the SRT in noise. For the
better performers, the test-retest difference was found to be smaller, while for
the poorer performers the difference increased. For the better performers, the
slope of the discrimination function at SRT (s50) was comparable to that for
individuals with normal hearing, while for the poorer performers the s50 tended
to be significantly reduced. CONCLUSIONS: As the CI users differed significantly
in their SRT and their s50, a unified discrimination function for CI users must
not be used. Further tailoring of the procedure may be required, especially for
poorer CI performers.
PMID- 25140603
TI - Reply from Theelen-van den Hoek, et al.
PMID- 25140604
TI - Effectiveness of questionnaires for screening hearing of school-age children: a
comprehensive literature review.
AB - OBJECTIVE: The purpose of this study was to review the literature on the
effectiveness of parent or teacher-completed questionnaires as a tool to screen
school-aged children for permanent hearing loss. DESIGN: A rapid evidence
assessment was completed to provide a summary of information published between
1980 and 2013 in English or Spanish. To identify relevant publications, a
database search was conducted using nine databases. STUDY SAMPLE: Seven studies
were identified for inclusion in the review. RESULTS: Authors of three of the
studies recommended use of the questionnaire as a method for screening hearing in
school-aged children, and authors of four of the studies did not recommend use of
the questionnaire. However, only one of the seven studies provided good evidence
that questionnaires are an effective way of identifying hearing loss among
children. CONCLUSIONS: There is insufficient evidence that parent or teacher
completed questionnaire screening can be reliably used to identify children in
need of further hearing assessment. It is clear that more research is needed
before concluding that questionnaires are an effective and low-cost tool for use
to screen children for permanent hearing loss.
PMID- 25140605
TI - Rationally designed, nontoxic, nonamyloidogenic analogues of human islet amyloid
polypeptide with improved solubility.
AB - Human islet amyloid polypeptide (hIAPP or amylin) is a polypeptide hormone
produced in the pancreatic beta-cells that plays a role in glycemic control.
hIAPP is deficient in type 1 and type 2 diabetes and is a promising adjunct to
insulin therapy. However, hIAPP rapidly forms amyloid, and its strong tendency to
aggregate limits its usefulness. The process of hIAPP amyloid formation is toxic
to cultured beta-cells and islets, and islet amyloid formation in vivo has been
linked to beta-cell death and islet graft failure. An analogue of hIAPP with a
weakened tendency to aggregate, denoted pramlintide (PM), has been approved for
clinical applications, but suffers from poor solubility, particularly at
physiological pH, and its unfavorable solubility profile prevents coformulation
with insulin. We describe a strategy for rationally designing analogues of hIAPP
with improved properties; key proline mutations are combined with substitutions
that increase the net charge of the molecule. An H18R/G24P/I26P triple mutant and
an H18R/A25P/S28P/S29P quadruple mutant are significantly more soluble at neutral
pH than hIAPP or PM. They are nonamyloidogenic and are not toxic to rat INS beta
cells. The approach is not limited to these examples; additional analogues can be
designed using this strategy. To illustrate this point, we show that an
S20R/G24P/I26P triple mutant and an H18R/I26P double mutant are nonamyloidogenic
and significantly more soluble than human IAPP or PM. These analogues and second
generation derivatives are potential candidates for the coformulation of IAPP
with insulin and other polypeptides.
PMID- 25140606
TI - Total syntheses of multicaulins via oxidative photocyclization of stilbenes.
AB - The Wittig reaction of 3-isopropyl-4-methoxybenzaldehyde and 2,3
dimethylbenzylphosphonium bromide afforded the corresponding stilbene mixture 16.
Oxidative photocyclization of stilbene 16 with iodine facilitated the first total
synthesis of 7-isopropyl-6-methoxy-1,2-dimethylphenanthrene, multicaulin (1). The
O-demethylation of 1 with BBr3 afforded the 7-isopropyl-1,2-dimethylphenanthren-6
ol, O-demethylmulticaulin (2).
PMID- 25140609
TI - Quantum yields and reaction times of photochromic diarylethenes: nonadiabatic ab
initio molecular dynamics for normal- and inverse-type.
AB - Photochromism is a light-induced molecular process that is likely to find its way
into future optoelectronic devices. In further optimization of photochromic
materials, light-induced conversion efficiencies as well as reaction times can
usually only be determined once a new molecule was synthesized. Here we use
nonadiabatic ab initio molecular dynamics to study the electrocyclic reaction of
diarylethenes, comparing normal- and inverse-type systems. Our study highlights
that reaction quantum yields can be successfully predicted in accord with
experimental findings. In particular, we find that inverse-type diarylethenes
show a significantly higher reaction quantum yield and cycloreversion on times
typically as short as 100 fs.
PMID- 25140607
TI - Stochastic kinetics on networks: when slow is fast.
AB - Most chemical and biological processes can be viewed as reaction networks in
which different pathways often compete kinetically for transformation of
substrates into products. An enzymatic process is an example of such phenomena
when biological catalysts create new routes for chemical reactions to proceed. It
is typically assumed that the general process of product formation is governed by
the pathway with the fastest kinetics at all time scales. In contrast to the
expectation, here we show theoretically that at time scales sufficiently short,
reactions are predominantly determined by the shortest pathway (in the number of
intermediate states), regardless of the average turnover time associated with
each pathway. This universal phenomenon is demonstrated by an explicit
calculation for a system with two competing reversible (or irreversible)
pathways. The time scales that characterize this regime and its relevance for
single-molecule experimental studies are also discussed.
PMID- 25140610
TI - A Cu(II) complex of an imidazolium-based ionic liquid: synthesis, X-ray structure
and application in the selective electrochemical sensing of guanine.
AB - An imidazolium-based ionic liquid containing a carboxylic acid group was
synthesized and complexed with Cu(II). The resulting complex R1 was fully
characterized using various techniques, including IR spectroscopy and X-ray
crystallography. Binding studies of the complex R1 were performed with anions and
biomolecules using cyclic voltammetry, which showed no change in its voltammogram
upon the addition of various anions and most biomolecules. However, a shift in
the reduction peak from +0.20 to -0.15 was observed upon the addition of guanine.
This selective determination of guanine by R1 was extended by using R1 as an
electrochemical sensor for guanine in various voltammetric techniques, including
cyclic voltammetry, LSV and DPV. The proposed sensor showed excellent
reproducibility and high selectivity and sensitivity towards guanine, with a
linear range of 0-20 MUM and a detection limit of 45 nM.
PMID- 25140611
TI - Transparent metallic fractal electrodes for semiconductor devices.
AB - Nanostructured metallic films have the potential to replace metal oxide films as
transparent electrodes in optoelectronic devices. An ideal transparent electrode
should possess a high, broadband, and polarization-independent transmittance.
Conventional metallic gratings and grids with wavelength-scale periodicities,
however, do not have all of these qualities. Furthermore, the transmission
properties of a nanostructured electrode need to be assessed in the actual
dielectric environment provided by a device, where a high-index semiconductor
layer can reflect a substantial fraction of the incident light. Here we propose
nanostructured aluminum electrodes with space-filling fractal geometries as
alternatives to gratings and grids and experimentally demonstrate their superior
optoelectronic performance through integration with Si photodetectors. As shown
by polarization and spectrally resolved photocurrent measurements, devices with
fractal electrodes exhibit both a broadband transmission and a flat polarization
response that outperforms both square grids and linear gratings. Finally, we show
the benefits of adding a thin silicon nitride film to the nanostructured
electrodes to further reduce reflection.
PMID- 25140613
TI - Molybdenum phosphide: a new highly efficient catalyst for the electrochemical
hydrogen evolution reaction.
AB - Molybdenum phosphide was adopted as a new electrocatalyst for the hydrogen
evolution reaction for the first time, exhibiting an excellent electrocatalytic
activity with a small Tafel slope of 60 mV dec(-1), which is amongst the most
active, acid-stable, earth abundant HER electrocatalysts reported to date.
PMID- 25140614
TI - Facile surface functionalization of hydrophobic magnetic nanoparticles.
AB - Nonpolar phase synthesized hydrophobic nanocrystals show attractive properties
and have demonstrated prominent potential in biomedical applications. However,
the preparation of biocompatible nanocrystals is made difficult by the presence
of hydrophobic surfactant stabilizer on their surfaces. To address this
limitation, we have developed a facile, high efficiency, single-phase and low
cost method to convert hydrophobic magnetic nanoparticles (MNPs) to an aqueous
phase using tetrahydrofuran, NaOH and 3,4-dihydroxyhydrocinnamic acid without any
complicated organic synthesis. The as-transferred hydrophilic MNPs are water
soluble over a wide pH range (pH = 3-12), and the solubility is pH-controllable.
Furthermore, the as-transferred MNPs with carboxylate can be readily adapted with
further surface functionalization, varying from small molecule dyes to
oligonucleotides and enzymes. Finally, the strategy developed here can easily be
extended to other types of hydrophobic nanoparticles to facilitate biomedical
applications of nanomaterials.
PMID- 25140615
TI - High-resolution Fourier transform ion cyclotron resonance mass spectrometry with
increased throughput for biomolecular analysis.
AB - A multielectrode ion cyclotron resonance (ICR) cell, herein referred to as the
"4X cell", for signal detection at the quadruple frequency multiple was
implemented and characterized on a commercial 10 T Fourier transform ICR mass
spectrometer (FT-ICR MS). Notably, with the 4X cell operating at a 10 T magnetic
field we achieved a 4-fold increase in MS acquisition rate per unit of resolving
power for signal detection periods typically employed in FTMS, viz., shorter than
6 s. Effectively, the obtained resolution performance represents the limit of the
standard measurement principle with dipolar signal detection and FT signal
processing at an equivalent magnetic field of 40 T. In other words, the achieved
resolving powers are 4 times higher than those provided by 10 T FT-ICR MS with a
standard ICR cell. For example, resolving powers of 170,000 and 70,000 were
obtained in magnitude-mode Fourier spectra of 768 and 192 ms apodized transient
signals acquired for a singly charged fluorinated phosphazine (m/z 1422) and a 19
fold charged myoglobin (MW 16.9 kDa), respectively. In peptide analysis, the
baseline-resolved isotopic fine structures were obtained with as short as 768 ms
transients. In intact protein analysis, the average resolving power of 340,000
across the baseline-resolved (13)C isotopic pattern of multiply charged ions of
bovine serum albumin was obtained with 1.5 s transients. The dynamic range and
the mass measurement accuracy of the 4X cell were found to be comparable to the
ones obtained for the standard ICR cell on the same mass spectrometer. Overall,
the reported results validate the advantages of signal detection at frequency
multiples for increased throughput in FT-ICR MS, essential for numerous
applications with time constraints, including proteomics.
PMID- 25140617
TI - New approach for the step by step control of magnetic nanostructure
functionalization.
AB - This paper describes the synthesis, functionalization, and multitechnique
analysis of magnetic nanoparticles. The synthetic method involves the covering of
a magnetite nucleus by a silica layer and the further functionalization with
different fluorophores via a cross-linker molecule. All synthetic intermediates
were analyzed by fluorescence spectroscopy and AC magnetic susceptibility. For
one of the considered molecules, a further investigation with STEM, EDXS, and DLS
has been conducted in order to validate the proposed magnetic results. The
comparison between the two techniques is used to ensure a complete
characterization of the product confirming the success of the synthesis. By
comparing the magnetic and the fluorescence measurements, we also demonstrate the
effectiveness of AC susceptibility as a robust and versatile technique to follow
the synthesis of complex magnetic nanostructures regardless of the nature of the
functionalization.
PMID- 25140618
TI - Tremendous effect of the morphology of birnessite-type manganese oxide
nanostructures on catalytic activity.
AB - The octahedral layered birnessite-type manganese oxide (OL-1) with the
morphologies of nanoflowers, nanowires, and nanosheets were prepared and
characterized with X-ray diffraction (XRD), scanning electron microscopy (SEM),
transmission electron microscopy (TEM), thermogravimetric/differential scanning
calorimetry (TG/DSC), Brunnauer-Emmett-Teller (BET), inductively coupled plasma
(ICP), and X-ray photoelectron spectroscopy (XPS). The OL-1 nanoflowers possess
the highest concentration of oxygen vacancies or Mn(3+), followed by the OL-1
nanowires and nanosheets. The result of catalytic tests shows that the OL-1
nanoflowers exhibit a tremendous enhancement in the catalytic activity for
benzene oxidation as compared to the OL-1 nanowires and nanosheets. Compared to
the OL-1 nanosheets, the OL-1 nanoflowers demonstrate an enormous decrease
(DeltaT(50) = 274 degrees C; DeltaT(90) > 248 degrees C) in reaction
temperatures T50 and T90 (corresponding to 50 and 90% benzene conversion,
respectively) for benzene oxidation. The origin of the tremendous effect of
morphology on the catalytic activity for the nanostructured OL-1 catalysts is
experimentally and theoretically studied via CO temperature-programmed reduction
(CO-TPR) and density functional theory (DFT) calculation. The tremendous
catalytic enhancement of the OL-1 nanoflowers compared to the OL-1 nanowires and
nanosheets is attributed to their highest surface area as well as their highest
lattice oxygen reactivity due to their higher concentration of oxygen vacancies
or Mn(3+), thus tremendously improving the catalytic activity for the benzene
oxidation.
PMID- 25140619
TI - High photosensitivity few-layered MoSe2 back-gated field-effect phototransistors.
AB - In this paper, we report on the fabrication and optoelectronic properties of high
sensitive phototransistors based on few-layered MoSe2 back-gated field-effect
transistors, with a mobility of 19.7 cm2 V-1 s-1 at room temperature. We obtained
an ultrahigh photoresponsivity of 97.1 AW-1 and an external quantum efficiency
(EQE) of 22 666% using 532 nm laser excitation at room temperature. The
photoresponsivity was improved near the threshold gate voltage; however, the
selection of the silicon dioxide as a gate oxide represents a limiting factor in
the ultimate performance. Thanks to their high photoresponsivity and external
quantum efficiency, the few-layered MoSe2-based devices are promising for
photoelectronic applications.
PMID- 25140621
TI - Guiding post-treatment decisions in rectal cancer: mrTRG is a practical place to
start.
PMID- 25140620
TI - Genomewide association studies for 50 agronomic traits in peanut using the
'reference set' comprising 300 genotypes from 48 countries of the semi-arid
tropics of the world.
AB - Peanut is an important and nutritious agricultural commodity and a livelihood of
many small-holder farmers in the semi-arid tropics (SAT) of world which are
facing serious production threats. Integration of genomics tools with on-going
genetic improvement approaches is expected to facilitate accelerated development
of improved cultivars. Therefore, high-resolution genotyping and multiple season
phenotyping data for 50 important agronomic, disease and quality traits were
generated on the 'reference set' of peanut. This study reports comprehensive
analyses of allelic diversity, population structure, linkage disequilibrium (LD)
decay and marker-trait association (MTA) in peanut. Distinctness of all the
genotypes can be established by using either an unique allele detected by a
single SSR or a combination of unique alleles by two or more than two SSR
markers. As expected, DArT features (2.0 alleles/locus, 0.125 PIC) showed lower
allele frequency and polymorphic information content (PIC) than SSRs (22.21
alleles /locus, 0.715 PIC). Both marker types clearly differentiated the
genotypes of diploids from tetraploids. Multi-allelic SSRs identified three sub
groups (K = 3) while the LD simulation trend line based on squared-allele
frequency correlations (r2) predicted LD decay of 15-20 cM in peanut genome.
Detailed analysis identified a total of 524 highly significant MTAs (p value >
2.1 * 10-6) with wide phenotypic variance (PV) range (5.81-90.09%) for 36 traits.
These MTAs after validation may be deployed in improving biotic resistance, oil/
seed/ nutritional quality, drought tolerance related traits, and yield/ yield
components.
PMID- 25140622
TI - Small steps that lead to a giant leap for prostate cancer patients.
PMID- 25140623
TI - Pelvic MRI for guiding treatment decisions in rectal cancer.
AB - Fluoropyrimidine-based chemoradiation (CRT) is used routinely for locally
advanced rectal cancer to shrink the tumor preoperatively, improve lateral
surgical clearance at total mesorectal excision, prevent local recurrence, and
preserve organ function. In Northern Europe, short-course preoperative
radiotherapy (SCPRT) is preferred to achieve locoregional control. However, with
recent improvements in the quality of surgery, in magnetic resonance imaging
(MRI), and in pathologic reporting, we question whether "routine" CRT or SCPRT
should be offered indiscriminately for all patients.MRI is considered the optimal
modality for locoregional staging and evaluation of the potential for an involved
circumferential resection margin. MRI also provides detailed anatomic information
for surgical planning, and may identify poor prognostic features, which influence
the way in which the pathologist processes specimens. MRI can predict the
likelihood of good/poor tumor response to neoadjuvant CRT and can categorize
responders/nonresponders following treatment.Using MRI to define the risk of both
local recurrence and metastatic spread allows clinicians to determine which
patients might benefit from or safely avoid neoadjuvant treatment. We have
arrived at these views after comparing data from published observational studies,
results from randomized trials, and outcome analyses of the Norwegian National
Cancer Registry.
PMID- 25140624
TI - MRI-based treatment decision making for rectal cancer.
PMID- 25140625
TI - Squamous cell carcinoma recurring to the great auricular nerve.
PMID- 25140626
TI - Expanding androgen- and androgen receptor signaling-directed therapies for
castration-resistant prostate cancer.
AB - The treatment landscape of castration-resistant prostate cancer (CRPC) has been
dramatically changed over the past years with the approval of several new drugs
for clinical use. These include androgen axis-targeted therapy and novel drugs
with different mechanisms of action, including immunotherapy (sipuleucel-T),
radiopharmaceuticals (radium-223), and chemotherapy (cabazitaxel). Based on the
growing knowledge that the main driver for patients progressing on standard
androgen deprivation therapy is persistent activation of the androgen receptor
(AR) signaling axis, new drugs were developed and demonstrated significant
efficacy in recent clinical trials, leading to the approval of abiraterone and
enzalutamide in several countries. In this article, we review the most recent
advances in AR-directed therapies for CRPC, promising new agents under
development, cross-resistance, and mechanisms of resistance for the new
generation AR-targeted agents.
PMID- 25140627
TI - Targeting the androgen receptor signaling axis to reduce testosterone levels in
prostate cancer: how low should we go?
PMID- 25140628
TI - The urology perspective on expanding androgen-targeted treatments for men with
castration-resistant prostate cancer.
PMID- 25140629
TI - ACR Appropriateness Criteria(r) nonsurgical treatment for locally advanced non
small-cell lung cancer: good performance status/definitive intent.
AB - Concurrent chemotherapy/radiotherapy has been considered the standard treatment
for patients with a good performance status and inoperable stage III non-small
cell lung cancer (NSCLC). Three-dimensional chemoradiation therapy and intensity
modulated radiation therapy have been reported to reduce toxicity and allow a
dose escalation to 70 Gy and beyond. However, the Radiation Therapy Oncology
Group 0617 trial recently showed that dose escalation from 60 Gy to 74 Gy with
concurrent chemotherapy in stage III NSCLC was associated with higher toxicity
and worse survival. A "one size fits all" treatment approach may need to be
changed and adapted to each patient's particular disease and unique
biologic/anatomic features, as well as the most appropriate radiotherapy
modalities for that patient. The American College of Radiology Appropriateness
Criteria are evidence-based guidelines for specific clinical conditions that are
reviewed every 3 years by a multidisciplinary expert panel. The guideline
development and review include an extensive analysis of current medical
literature from peer-reviewed journals and the application, by the panel, of a
well-established consensus methodology (modified Delphi technique) to rate the
appropriateness of imaging and treatment procedures. In instances in which
evidence is lacking or not definitive, expert opinion may be used as the basis
for recommending imaging or treatment.
PMID- 25140632
TI - An ultrasonic contactless sensor for breathing monitoring.
AB - The monitoring of human breathing activity during a long period has multiple
fundamental applications in medicine. In breathing sleep disorders such as apnea,
the diagnosis is based on events during which the person stops breathing for
several periods during sleep. In polysomnography, the standard for sleep
disordered breathing analysis, chest movement and airflow are used to monitor the
respiratory activity. However, this method has serious drawbacks. Indeed, as the
subject should sleep overnight in a laboratory and because of sensors being in
direct contact with him, artifacts modifying sleep quality are often observed.
This work investigates an analysis of the viability of an ultrasonic device to
quantify the breathing activity, without contact and without any perception by
the subject. Based on a low power ultrasonic active source and transducer, the
device measures the frequency shift produced by the velocity difference between
the exhaled air flow and the ambient environment, i.e., the Doppler effect. After
acquisition and digitization, a specific signal processing is applied to separate
the effects of breath from those due to subject movements from the Doppler
signal. The distance between the source and the sensor, about 50 cm, and the use
of ultrasound frequency well above audible frequencies, 40 kHz, allow monitoring
the breathing activity without any perception by the subject, and therefore
without any modification of the sleep quality which is very important for sleep
disorders diagnostic applications. This work is patented (patent pending 2013-7
31 number FR.13/57569).
PMID- 25140631
TI - Intra-and-inter species biomass prediction in a plantation forest: testing the
utility of high spatial resolution spaceborne multispectral RapidEye sensor and
advanced machine learning algorithms.
AB - The quantification of aboveground biomass using remote sensing is critical for
better understanding the role of forests in carbon sequestration and for informed
sustainable management. Although remote sensing techniques have been proven
useful in assessing forest biomass in general, more is required to investigate
their capabilities in predicting intra-and-inter species biomass which are mainly
characterised by non-linear relationships. In this study, we tested two machine
learning algorithms, Stochastic Gradient Boosting (SGB) and Random Forest (RF)
regression trees to predict intra-and-inter species biomass using high resolution
RapidEye reflectance bands as well as the derived vegetation indices in a
commercial plantation. The results showed that the SGB algorithm yielded the best
performance for intra-and-inter species biomass prediction; using all the
predictor variables as well as based on the most important selected variables.
For example using the most important variables the algorithm produced an R2 of
0.80 and RMSE of 16.93 t.ha-1 for E. grandis; R2 of 0.79, RMSE of 17.27 t.ha-1
for P. taeda and R2 of 0.61, RMSE of 43.39 t.ha-1 for the combined species data
sets. Comparatively, RF yielded plausible results only for E. dunii (R2 of 0.79;
RMSE of 7.18 t.ha-1). We demonstrated that although the two statistical methods
were able to predict biomass accurately, RF produced weaker results as compared
to SGB when applied to combined species dataset. The result underscores the
relevance of stochastic models in predicting biomass drawn from different species
and genera using the new generation high resolution RapidEye sensor with
strategically positioned bands.
PMID- 25140630
TI - Expression of autophagy-related proteins according to androgen receptor and HER-2
status in estrogen receptor-negative breast cancer.
AB - PURPOSE: The purpose of this study was to investigate the expression of autophagy
related proteins in relation to androgen receptor (AR) status in estrogen
receptor (ER)-negative breast cancers. METHODS: We extracted 334 ER-negative
breast cancer samples to construct tissue microarrays (TMAs), which were
immunohistochemically stained for autophagy-related proteins (beclin-1, LC3A,
LC3B, p62) and for AR and HER-2. RESULTS: There were 127 AR-positive cases and
207 AR-negative cases, and 140 HER-2-positive cases and 194 HER-2 negative cases.
The AR-negative group was associated with tumoral LC3A expression (P<0.001),
while the AR-positive group was associated with tumoral BNIP3 expression
(P<0.001). Tumoral LC3A was most highly expressed in the AR-negative and HER-2
negative group, while stromal LC3A showed the highest expression in the AR
negative and HER-2-positive group. Tumoral BNIP3 and stromal BNIP3 were highest
in the AR-positive and HER-2-negative group. In the AR-positive and HER-2
negative group, stromal p62 positivity was an independent factor that was
statistically significant in its association with shorter disease-free survival
(DFS) (Hazard ratio: 10.21, 95% CI: 1.130-92.31, P = 0.039). Shorter DFS was
associated with tumoral LC3A positivity (Hazard ratio: 10.28, 95% CI: 2.068
51.19, P = 0.004) in the AR-negative and HER-2-positive group. CONCLUSION: In ER
negative breast cancers, AR status was associated with expression of different
types of autophagy-related proteins. Tumoral LC3A was most highly expressed in AR
negative breast cancers, while tumor BNIP3 was highest in AR-positive breast
cancers.
PMID- 25140633
TI - Directional navigation improves opportunistic communication for emergencies.
AB - We present a novel direction based shortest path search algorithm to guide
evacuees during an emergency. It uses opportunistic communications (oppcomms)
with low-cost wearable mobile nodes that can exchange packets at close range of a
few to some tens of meters without help of an infrastructure. The algorithm seeks
the shortest path to exits which are safest with regard to a hazard, and is
integrated into an autonomous Emergency Support System (ESS) to guide evacuees in
a built environment. The algorithm proposed that ESSs are evaluated with the DBES
(Distributed Building Evacuation Simulator) by simulating a shopping centre where
fire is spreading. The results show that the directional path finding algorithm
can offer significant improvements for the evacuees.
PMID- 25140634
TI - Rapid, single-molecule assays in nano/micro-fluidic chips with arrays of closely
spaced parallel channels fabricated by femtosecond laser machining.
AB - Cost-effective pharmaceutical drug discovery depends on increasing assay
throughput while reducing reagent needs. To this end, we are developing an
ultrasensitive, fluorescence-based platform that incorporates a nano/micro
fluidic chip with an array of closely spaced channels for parallelized optical
readout of single-molecule assays. Here we describe the use of direct femtosecond
laser machining to fabricate several hundred closely spaced channels on the
surfaces of fused silica substrates. The channels are sealed by bonding to a
microscope cover slip spin-coated with a thin film of poly(dimethylsiloxane).
Single-molecule detection experiments are conducted using a custom-built, wide
field microscope. The array of channels is epi-illuminated by a line-generating
red diode laser, resulting in a line focus just a few microns thick across a 500
micron field of view. A dilute aqueous solution of fluorescently labeled
biomolecules is loaded into the device and fluorescence is detected with an
electron-multiplying CCD camera, allowing acquisition rates up to 7 kHz for each
microchannel. Matched digital filtering based on experimental parameters is used
to perform an initial, rapid assessment of detected fluorescence. More detailed
analysis is obtained through fluorescence correlation spectroscopy. Simulated
fluorescence data is shown to agree well with experimental values.
PMID- 25140635
TI - A Kalman filter-based short baseline RTK algorithm for single-frequency
combination of GPS and BDS.
AB - The emerging Global Navigation Satellite Systems (GNSS) including the BeiDou
Navigation Satellite System (BDS) offer more visible satellites for positioning
users. To employ those new satellites in a real-time kinematic (RTK) algorithm to
enhance positioning precision and availability, a data processing model for the
dual constellation of GPS and BDS is proposed and analyzed. A Kalman filter-based
algorithm is developed to estimate the float ambiguities for short baseline
scenarios. The entire work process of the high-precision algorithm based on the
proposed model is deeply investigated in detail. The model is validated with real
GPS and BDS data recorded from one zero and two short baseline experiments.
Results show that the proposed algorithm can generate fixed baseline output with
the same precision level as that of either a single GPS or BDS RTK algorithm. The
significantly improved fixed rate and time to first fix of the proposed method
demonstrates a better availability and effectiveness on processing multi-GNSSs.
PMID- 25140636
TI - Estimation of spatial-temporal gait parameters using a low-cost ultrasonic motion
analysis system.
AB - In this paper, a low-cost motion analysis system using a wireless ultrasonic
sensor network is proposed and investigated. A methodology has been developed to
extract spatial-temporal gait parameters including stride length, stride
duration, stride velocity, stride cadence, and stride symmetry from 3D foot
displacements estimated by the combination of spherical positioning technique and
unscented Kalman filter. The performance of this system is validated against a
camera-based system in the laboratory with 10 healthy volunteers. Numerical
results show the feasibility of the proposed system with average error of 2.7%
for all the estimated gait parameters. The influence of walking speed on the
measurement accuracy of proposed system is also evaluated. Statistical analysis
demonstrates its capability of being used as a gait assessment tool for some
medical applications.
PMID- 25140637
TI - Pyridylenevinylene based Cu(2+)-specific, injectable metallo(hydro)gel:
thixotropy and nanoscale metal-organic particles.
AB - A Cu(2+)-selective metallo(hydro)gelation of a p-pyridyl ended oligo
phenylenevinylene system is reported over its respective meta- and ortho
regioisomers. The metallogel formed via the self-assembly of the nanoscale-metal
organic particles is injectable and also shows multi-stimuli responsiveness,
including thixotropy.
PMID- 25140638
TI - Experience of nurses caring for child with hematopoietic stem cell
transplantation in general pediatric ward: a descriptive phenomenological
approach.
AB - BACKGROUND: Most studies on hematopoietic stem cell transplantation (HSCT) have
focused on patients, survivors, or their family members, such as siblings and
parents. Little attention has been paid to nurses caring for HSCT pediatric
patients and in particular in a Taiwanese context. OBJECTIVE: The objective of
this study was to explore nurses' lived experience caring for HSCT children in
isolation within a general pediatric ward. METHOD: A Husserlian phenomenological
approach informed the exploration of the meaning and essence of the nurses'
caring experience. Data were collected using semistructured interviews. RESULTS:
Twelve nurses were interviewed. Analysis of interviews yielded 3 main themes:
being worried about ruining transplantation success, feeling loss of control in
handling suffering, and reflecting upon the value of HSCT. CONCLUSIONS: Nurses
felt the stress of caring for HSCT children because of the heavy workload and the
pressure of responsibility. Witnessing the suffering of patients/families was
particularly stressful. However, nurses were helped to overcome this stress by
looking at the value and meaning of HSCT. IMPLICATIONS FOR PRACTICE: Nurses need
practical support from nursing leaders in terms of carefully organizing patient
care, controlling the nurse-to-patient ratio, and offering a safe work
environment by providing systematic formal training on HSCT and receiving proper
supervision. Understanding and learning are gained from nurses who are able to
seek meaning from HSCT through appreciating every caregiving effort and through
valuing how their nursing role contributes to the quality of patients' care.
PMID- 25140640
TI - Psychometric properties of a Chinese version of the Colorectal Cancer Perceptions
Scale in a sample of older Chinese people.
AB - BACKGROUND: Older adults are more susceptible to colorectal cancer (CRC).
Psychosocial constructs in the Health Belief Model are targets for interventional
studies. No tool to measure these beliefs of older Chinese people has been
validated. OBJECTIVE: The present study aimed to examine the preliminary
psychometric properties of the Chinese version of the Colorectal Cancer
Perceptions Scale (CRCPS). METHODS: The CRCPS was translated to Chinese language,
validated by an expert panel, and tested. Interviewer-administered surveys were
carried out with a convenience sample of 219 community-dwelling Chinese adults 60
years or older and were included in the analysis. RESULTS: Six factors were
retained, with items on susceptibility and benefits remaining as designed,
whereas those on severity formed 2 factors, labeled severity-fear and severity
life impact, and those on barriers again formed 2 factors, labeled psychological
barriers and knowledge barriers. Cronbach's alpha values ranged from .74 to .88,
and test-retest reliability correlations ranged from .38 for psychological
barriers to .69 for knowledge barriers. Respondents who had undergone CRC
screening had significantly lower mean scores on severity-fear, severity-life
impact, psychological barriers, and knowledge barriers compared with those who
had not. CONCLUSIONS: The results provide preliminary support for the reliability
and validity of the Chinese version of the CRCPS. Further psychometric testing is
recommended. IMPLICATIONS FOR PRACTICE: The survey provides a useful tool to
assess CRC health beliefs, which interventions should address to improve
screening rates among older Chinese adults.
PMID- 25140639
TI - Physician and nurse beliefs of phase 1 trials in pediatric oncology.
AB - BACKGROUND: In order to improve the survival of children with cancer, novel
therapies must be identified. Promising agents are tested in phase 1 trials in
order to identify appropriate dosing and describe toxicity in children. The
identification and referral of candidate patients for phase 1 trials rely heavily
on medical providers who must balance their own perceptions of phase 1 trials
with the desires and willingness of the patient and his/her family. OBJECTIVE:
The goal of the present study was to evaluate and compare physician and nurse
perceptions regarding the beliefs, expectations, and perceived benefits of phase
1 clinical trials. METHODS: A survey consisting of 21 questions was sent to 419
physicians and nurses practicing pediatric oncology at 30 different institutions.
With the exception of 10 demographic questions, items were either rank ordered or
rated on 5-point Likert scales. RESULTS: Ninety-four physicians and 122 nurses
completed the online survey. Physicians and nurses differed in their knowledge of
the goals and medical effects of phase 1 clinical trials. CONCLUSIONS: Physicians
and nurses hold positive beliefs regarding phase 1 clinical trials and support
their role in the treatment of children with cancer. Education is necessary to
increase nurses' knowledge of the goals and outcomes. IMPLICATIONS FOR PRACTICE:
These findings suggest that continued education of nurses as well as physicians
about the goals, execution, and monitoring of phase 1 therapy would be
worthwhile.
PMID- 25140642
TI - [The hazing and the ethical responsibility of the future doctors].
PMID- 25140643
TI - [Value of tissue biomarkers and pet-ct in the prognosis of head and neck cancer:
review of diagnostic and therapeutic paradigm].
PMID- 25140641
TI - Enhancement of biological reactions on cell surfaces via macromolecular crowding.
AB - The reaction of macromolecules such as enzymes and antibodies with cell surfaces
is often an inefficient process, requiring large amounts of expensive reagent.
Here we report a general method based on macromolecular crowding with a range of
neutral polymers to enhance such reactions, using red blood cells (RBCs) as a
model system. Rates of conversion of type A and B red blood cells to universal O
type by removal of antigenic carbohydrates with selective glycosidases are
increased up to 400-fold in the presence of crowders. Similar enhancements are
seen for antibody binding. We further explore the factors underlying these
enhancements using confocal microscopy and fluorescent recovery after bleaching
(FRAP) techniques with various fluorescent protein fusion partners. Increased
cell-surface concentration due to volume exclusion, along with two-dimensionally
confined diffusion of enzymes close to the cell surface, appear to be the major
contributing factors.
PMID- 25140645
TI - Impact of bariatric surgery on depression and anxiety symptons, bulimic behaviors
and quality of life.
AB - OBJECTIVE: To assess psychiatric symptoms, substance use, quality of life and
eating behavior of patients undergoing bariatric surgery before and after the
procedure. METHODS: We conducted a prospective longitudinal study of 32 women
undergoing bariatric surgery. To obtain data, the patients answered specific,
self-administered questionnaires. RESULTS: We observed a reduction in depressive
and anxious symptoms and also in bulimic behavior, as well as an improved quality
of life in the physical, psychological and environmental domains. There was also
a decrease in use of antidepressants and appetite suppressants, but the surgery
was not a cessation factor in smoking and / or alcoholism. CONCLUSION: a decrease
in psychiatric symptoms was observed after bariatric surgery, as well as the
reduction in the use of psychoactive substances. In addition, there was an
improvement in quality of life after surgical treatment of obesity.
PMID- 25140644
TI - The cost of excessive postoperative use of antimicrobials: the context of a
public hospital.
AB - OBJECTIVE: To evaluate the improper use of antimicrobials during the
postoperative period and its economic impact. METHODS: We conducted a prospective
cohort study by collecting data from medical records of 237 patients operated on
between 01/11/08 and 31/12/08. RESULTS: from the 237 patients with the
information collected, 217 (91.56%) received antimicrobials. During the
postoperative period, 125 (57.7%) patients received more than two antimicrobials.
On average, 1.7 +/- 0.6 antimicrobials were prescribed to patients, the most
commonly prescribed antibiotic being cephalothin, in 41.5% (154) of cases. The
direct cost of antimicrobial therapy accounted for 63.78% of all drug therapy,
this large percentage being attributed in part to the extended antimicrobial
prophylaxis. In the case of clean operations, where there was a mean duration of
5.2 days of antibiotics, antimicrobials represented 44.3% of the total therapy
cost. CONCLUSION: The data illustrate the impact of overuse of antimicrobials,
with questionable indications, creating situations that compromise patient safety
and increasing costs in the assessed hospital.
PMID- 25140646
TI - Implementation of a perioperative management protocol for patients undergoing
orthopedic surgery.
AB - OBJECTIVE: To evaluate the initial results after the implementation of
perioperative protocol in patients over 60 years of age undergoing surgical
treatment for femur fractures. METHODS: We conducted a prospective study of
patients older than 60 years who were hospitalized with femur fracture. They were
operated under spinal anesthesia and analgesia by lumbar plexus blockade. Data
evaluation was performed before arrival in the operating room during surgery, in
the post-anesthesia recovery room and in the ward the next morning of the
operation. RESULTS: 105 patients underwent various types of surgical corrections
of the femur. The hospital stay ranged from three to 86 days. Fasting ranged from
9h15min to 19h30mn. Hypotension occurred in 5.7%. The duration of motor blockade
ranged from 1h45min to 5h30imn. Maltodextrin feeding ranged from 50min to 3h45min
and the time spent in the post-anesthetic care unit ranged from 50 minutes to 4
hours. Onset of oral intake in the ward ranged from 4hto 8h15min. The duration of
anesthesia ranged from 14 to 33 hours. No patient required a urinary catheter,
nor was transferred to the ICU. All patients were able to be discharged on the
first postoperative day. CONCLUSION: The use of a protocol to accelerate the
postoperative period may reduce the fasting time, length of hospital stay and
provide faster i discharge n elderly patients with femur fractures.
PMID- 25140647
TI - Association between peripheral arterial disease and C-reactive protein in the
Japanese-Brazilian population.
AB - OBJECTIVE: To evaluate the relationship between peripheral arterial disease and
elevated levels of C-reactive protein in the Japanese-Brazilian population of
high cardiovascular risk. METHODS: We conducted a cross-sectional study derived
from a population-based study on the prevalence of diabetes and associated
diseases in the Japanese-Brazilian population. One thousand, three hundred and
thirty individuals aged e" 30 underwent clinical and laboratory examination,
including measurement of ultrasensitive C-reactive protein. The diagnosis of
peripheral arterial disease was performed by calculating the ankle-brachial
index. We considered with peripheral arterial disease patients who had ankle
brachial index d" 0.9. After applying the exclusion criteria, 1,038 subjects
completed the study. RESULTS: The mean age of the population was 56.8 years; 46%
were male. The prevalence of peripheral arterial disease was 21%, with no
difference between genders. Data analysis showed no association between
peripheral arterial disease and ultrasensitive C-reactive protein. Patients with
ankle-brachial index d" 0.70 showed higher values of ultrasensitive C-reactive
protein and worse cardiometabolic profile. We found a positive independent
association of peripheral arterial disease with hypertension and smoking.
CONCLUSION: The association between low levels of ankle-brachial index and
elevated levels of ultrasensitive C-reactive protein may suggest a relationship
of gravity, aiding in the mapping of high-risk patients.
PMID- 25140648
TI - Haematological and biochemical characteristics of the splenic effluent blood in
schistosomal patients undergoing splenectomy.
AB - OBJECTIVE: To assess hematological and biochemical features of splenic effluent
blood and their influence on the rise of hematological values after splenectomy.
METHODS: we studied 20 patients undergoing surgical treatment for schistosomatic
portal hypertension. We collected blood samples for CBC, coagulation, bilirubin
and albumin in the splenic vein (perioperative) and peripheral blood (immediately
pre and postoperative periods). RESULTS: the splenic blood showed higher values
of red blood cells, hemoglobin, hematocrit, platelet count, total leukocytes,
neutrophils, lymphocytes, monocytes, eosinophils and basophils, as well as
reduction of laboratory coagulation parameters in relation to peripheral blood
collected preoperatively. In the postoperative peripheral blood there was an
increase in the overall leukocytes and in their neutrophil component, and
decreased levels of basophils, eosinophils and lymphocytes. The other
postoperative variables of complete blood count and coagulation tests were not
different compared with the splenic blood. The albumin values were lower
postoperatively when compared to preoperative and splenic blood. There were
higher values of direct bilirubin in the postoperative period when compared with
the preoperative and splenic blood. Postoperative indirect bilirubin was lower
compared to its value in the splenic blood. CONCLUSION: hematological and
biochemical values of splenic effluent blood are higher than those found in
peripheral blood in the presence of schistosomal splenomegaly. However, the
splenic blood effluent is not sufficient to raise the blood levels found after
splenectomy.
PMID- 25140649
TI - Standardization of pulmonary ventilation technique using volume-controlled
ventilators in rats with congenital diaphragmatic hernia.
AB - OBJECTIVE: To standardize a technique for ventilating rat fetuses with Congenital
Diaphragmatic Hernia (CDH) using a volume-controlled ventilator. METHODS:
Pregnant rats were divided into the following groups: a) control (C); b) exposed
to nitrofen with CDH (CDH); and c) exposed to nitrofen without CDH (N-). Fetuses
of the three groups were randomly divided into the subgroups ventilated (V) and
non-ventilated (N-V). Fetuses were collected on day 21.5 of gestation, weighed
and ventilated for 30 minutes using a volume-controlled ventilator. Then the
lungs were collected for histological study. We evaluated: body weight (BW),
total lung weight (TLW), left lung weight (LLW), ratios TLW / BW and LLW / BW,
morphological histology of the airways and causes of failures of ventilation.
RESULTS: BW, TLW, LLW, TLW / BW and LLW / BW were higher in C compared with N- (p
<0.05) and CDH (p <0.05), but no differences were found between the subgroups V
and N-V (p> 0.05). The morphology of the pulmonary airways showed hypoplasia in
groups N- and CDH, with no difference between V and N-V (p <0.05). The C and N-
groups could be successfully ventilated using a tidal volume of 75 il, but the
failure of ventilation in the CDH group decreased only when ventilated with 50
il. CONCLUSION: Volume ventilation is possible in rats with CDH for a short
period and does not alter fetal or lung morphology.
PMID- 25140650
TI - Modified method for bronchial suture by Ramirez Gama compared to separate
stitches suture: experimental study.
AB - OBJECTIVE: To experimentally compare two classic techniques described for manual
suture of the bronchial stump. METHODS: We used organs of pigs, with isolated
trachea and lungs, preserved by refrigeration. We dissected 30 bronchi, which
were divided into three groups of ten bronchi each, of 3mm, 5mm, and 7mm,
respectively. In each, we performed the suture with simple, separated,
extramucosal stitches in five other bronchi, and the technique proposed by
Ramirez and modified by Santos et al in the other five. Once the sutures were
finished, the anastomoses were tested using compressed air ventilation, applying
an endotracheal pressure of 20mmHg. RESULTS: the Ramirez Gama suture was more
effective in the bronchi of 3, 5 and 7 mm, and there was no air leak even after
subjecting them to a tracheal pressure of 20mmHg. The simple interrupted sutures
were less effective, with extravasation in six of the 15 tested bronchi,
especially in the angles of the sutures. These figures were not significant (p =
0.08). CONCLUSION: manual sutures of the bronchial stumps were more effective
when the modified Ramirez Gama suture was used in the caliber bronchi arms when
tested with increased endotracheal pressure.
PMID- 25140652
TI - Comparison between electrocautery and fibrin selant after hepatectomy in rats.
AB - OBJECTIVE: To compare between electrocautery and fibrin sealant hemostasis in
rats after partial hepatectomy. METHODS: we used 24 Wistar rats, which were
submitted to 30% hepatic resection, divided into two groups of 12 animals each:
Group Electrocautery and Group Tachosil(r). These animals were evaluated after
three and 14 days. We assessed the presence of complications, laboratory tests
and histological exam of the recovered liver. RESULTS: the presence of abscess
was more prevalent in the electrocautery group. The observed adhesions were more
pronounced in the electrocautery group, both in frequency and in intensity, after
three and 14 days. There were no deaths in either group. As for laboratory
analysis, after three days the hematocrit was lower in the TachoSil(r) Group. The
elevation of AST and ALT were more pronounced in the electrocautery group (p =
0.002 and p = 0.004) in three days. Histological analysis of specimens collected
on the third day after surgery showed similar results in both groups for the
presence of polymorphonuclear cells, whereas mononuclear was more evident in the
TachoSil(r) group. We also observed that angiogenesis, although present in both
groups, was more pronounced in the TachoSil(r) group (p = 0.030). However, on the
14th day angiogenesis was more pronounced in the electrocautery group, but
without statistical significance. CONCLUSION: hemostasis achieved by the groups
was similar; however, the use of electrocautery was associated with infections,
adhesions at higher grades and elevated liver enzymes.
PMID- 25140651
TI - Effect of the celexoxib in microscopic changes of the esophageal mucosal of rats
induced by esofagojejunostomy.
AB - OBJECTIVE: To evaluate the protective effect of celecoxib in the esophageal
mucosa in rats undergoing esofagojejunostomy. METHODS: Sixty male Wistar rats
from the vivarium of the University of Health Sciences of Alagoas were used for
the experiment. The animals were divided into four groups: Group I, 15 rats
undergoing esofagojejunostomy with the use of celecoxib postoperatively; Group
II, 15 rats undergoing esofagojejunostomy without the use of celecoxib; Group
III, 15 rats undergoing celiotomy with bowel manipulation; and Group IV, 15 rats
without surgery and using celecoxib. The observation period was 90 days. After
the death of the animals, the distal segment of the esophagus was resected and
sent for microscopic analysis. RESULTS: esofagojejunostomy caused macroscopic and
microscopic esophagitis. Esophagitis was equal in both groups I and II. In groups
III and IV esophageal lesions were not developed. CONCLUSIONS: celecoxib had
neither protective nor inducing effect on esophagitis, but had a protective
effect on dysplasia of the animals of group I.
PMID- 25140654
TI - Surgical treatment of cleft lip.
AB - We performed a systematic review of the literature on the surgical treatment of
cleft lip, emphasizing the prevalence, complications associated with the
treatment and the points of disagreement between authors. We conducted a
literature cross-sectional search that analyzed publications in books, articles
and on the databases SciELO - Scientific Electronic Library Online, PubMed, of
the National Center for Biotechnology Information. We conclude that: 1) the
severity of the cleft will indicate the technique presenting more advantages; 2)
the different approaches indicate that there is no consensus on the optimal
technique; and 3) the surgeon experience contributes to choosing the best option.
PMID- 25140653
TI - Sirolimus influence on hepatectomy-induced liver regeneration in rats.
AB - OBJECTIVE: To evaluate the influence of sirolimus on liver regeneration triggered
by resection of 70% of the liver of adult rats. METHODS: we used 40 Wistar rats
randomly divided into two groups (study and control), each group was divided into
two equal subgroups according to the day of death (24 hours and seven days).
Sirolimus was administered at a dose of 1mg/kg in the study group and the control
group was given 1 ml of saline. The solutions were administered daily since three
days before hepatectomy till the rats death to removal of the regenerated liver,
conducted in 24 hours or 7 days after hepatectomy. Liver regeneration was
measured by the KWON formula, by the number of mitotic figures (hematoxylin-eosin
staining) and by the immunohistochemical markers PCNA and Ki-67. RESULTS: there
was a statistically significant difference between the 24h and the 7d groups.
When comparing the study and control groups in the same period, there was a
statistically significant variation only for Ki-67, in which there were increased
numbers of hepatocytes in cell multiplication in the 7d study group compared with
the 7d control group (p = 0.04). CONCLUSION: there was no negative influence of
sirolimus in liver regeneration and there was a positive partial effect at
immunohistochemistry with Ki-67.
PMID- 25140655
TI - Four-arm single docking full robotic surgery for low rectal cancer: technique
standardization.
AB - The authors present the four-arm single docking full robotic surgery to treat low
rectal cancer. The eight main operative steps are: 1- patient positioning; 2-
trocars set-up and robot docking; 3- sigmoid colon, left colon and splenic
flexure mobilization (lateral-to-medial approach); 4-Inferior mesenteric artery
and vein ligation (medial-to-lateral approach); 5- total mesorectum excision and
preservation of hypogastric and pelvic autonomic nerves (sacral dissection,
lateral dissection, pelvic dissection); 6- division of the rectum using an endo
roticulator stapler for the laparoscopic performance of a double-stapled coloanal
anastomosis (type I tumor); 7- intersphincteric resection, extraction of the
specimen through the anus and lateral-to-end hand sewn coloanal anastomosis (type
II tumor); 8- cylindric abdominoperineal resection, with transabdominal section
of the levator muscles (type IV tumor). The techniques employed were safe and
have presented low rates of complication and no mortality.
PMID- 25140656
TI - [Is professional recognition in plastic surgery related to activity in research].
AB - OBJECTIVE: To evaluate the relation of medical research, with the participation
of prominent plastic surgeon in Congress. METHODS: We reviewed the scientific
programs of the last 3 Brazilian Congress of Surgery, were selected 21 Brazilian
plastic surgeons invited to serve as panelists or speakers in roundtable sessions
in the last 3 congresses (Group 1). We randomly selected and paired by other
members (associates) of the Brazilian Society of Plastic Surgery, with no
participation in congress as speaker (Group 2). We conducted a search for
articles published in journals indexed in Medline, Lilacs and SciELO for all
doctors selected during the entire academic career and the last 5 years from
March 2007 until March 2012. We assessed the research activity through the simple
counting of the number of publications in indexed journals for each professional.
The number of publications groups was compared. RESULTS: articles produced
throughout career: Group 1- 639 articles (average of 30.42 items each). Group 2-
79 articles (mean 3.95 articles each). Difference between medias: p <0.001.
CONCLUSION: The results demonstrate that the Brazilian Society of Plastic Surgery
seeking professionals with a greater number of publications and journals of
higher impact. This approach encourages new members to pursue a higher
qualification, and give security to congressmen, they can rely on the existence
of a technical criterion in the choice of speakers.
PMID- 25140657
TI - Is there a role for pyloric exclusion after severe duodenal trauma?
AB - Duodenal trauma is an infrequent injury, but linked to high morbidity and
mortality. Surgical management of duodenal injuries is dictated by: patient's
hemodynamic status, injury severity, time of diagnosis, and presence of
concomitant injuries. Even though most cases can be treated with primary repair,
some experts advocate adjuvant procedures. Pyloric exclusion (PE) has emerged as
an ancillary method to protect suture repair in more complex injuries. However,
the effectiveness of this procedure is debatable. The "Evidence Based
Telemedicine - Trauma & Acute Care Surgery" (EBT-TACS) Journal Club performed a
critical appraisal of the literature and selected three relevant publications on
the indications for PE in duodenal trauma. The first study retrospectively
compared 14 cases of duodenal injuries greater than grade II treated by PE, with
15 cases repaired primarily, all of which penetrating. Results showed that PE did
not improve outcome. The second study, also retrospective, compared primary
repair (34 cases) with PE (16 cases) in blunt and penetrating grade > II duodenal
injuries. The authors concluded that PE was not necessary in all cases. The third
was a literature review on the management of challenging duodenal traumas. The
author of that study concluded that PE is indicated for anastomotic leak
management after gastrojejunostomies. In conclusion, the choice of the surgical
procedure to treat duodenal injuries should be individualized. Moreover, there is
insufficient high quality scientific evidence to support the abandonment of PE in
severe duodenal injuries with extensive tissue loss.
PMID- 25140659
TI - Multinucleate cell angiohistiocytoma: clinicopathological correlation of 142
cases with insights into etiology and pathogenesis.
AB - INTRODUCTION: Multinucleate cell angiohistiocytoma (MCAH) is a peculiar
dermatopathological entity described as asymptomatic grouped red-to-violaceous
papules, developing over weeks to months without spontaneous regression. The
histopathological findings comprise bizarre basophilic multinucleated cells (MC),
small vessel inflammation, mild dermal fibrosis, and a sparse lymphohistiocytic
infiltrate. AIMS AND METHODS: This study aimed to collate and analyze the
clinical, histological, and immunohistochemical characteristics of all reported
cases of MCAH from the international literature, and the presence or absence of
concurrent chronic inflammatory or neoplastic phenomena to investigate any
potential clinicopathological correlations, which may hint at the underlying
pathophysiology of this condition. A systematic review of the literature was
undertaken with information collected by a predeveloped pro forma. New case
reports were also sourced from patient records at the Skin and Cancer Foundation
Australia Database. RESULTS: A total of 142 cases of MCAH were collated,
including 8 new case reports. The average age of onset was 50.1 years, with 79%
of all individuals being female. The most commonly affected areas were the hands
(30%) and face (29%). Univariate analysis revealed a positive association between
lesion size and MC staining for CD68 (R = 0.488; P = 0.004), and an inverse
relationship between size and endothelial staining for CD34 (R = -0.530; P =
0.012). Multiple lesions were significantly associated with an inverse
relationship to MC staining of CD68 (R = -0.519; P = 0.002). Moderate
correlations were seen between specific sites of vascularity and sites in which
MCs were identified (R = 0.734-0.741; P < 0.001), and dermal fibrosis was
associated with an increased number of MCs (R = 0.522; P = 0.002) and decreased
multinucleate cell immunohistochemical staining (R = -0.655; P = 0.003). An
association was found between patients with chronic inflammatory conditions and
endothelial staining for CD68 (R = 0.671; P = 0.012), and an inverse relationship
with MC staining for factor XIIIa (-0.481; P < 0.001). No statistically
significant relationships between neoplasia and MCAH were found. DISCUSSION AND
CONCLUSIONS: From the data examined, we hypothesize that although this condition
may be inflammatory and vascular in initial origin, fibrosis and atrophy play a
vital role in the pathogenesis, particularly regarding the progression to
multiple lesions. A detailed hypothesis is described that may be amenable to more
detailed investigations. Limitations in this study include the heterogeneity of
results analyzed across case reports; however, our conclusions match those
developed through the analysis of our case series. These hypotheses and proposals
provide an experimental basis for further research into the pathogenesis and
mechanisms underlying MCAH.
PMID- 25140660
TI - A unique case of a cutaneous lesion resembling mammary analog secretory
carcinoma: a case report and review of the literature.
AB - Mammary analog secretory carcinoma (MASC) is a rare type of salivary gland tumor
named for its morphological and genetic similarity to secretory carcinoma of the
breast. These tumors are most often found in the parotid gland but have been
described in several other mucosal locations of the head and neck. In this case
report, a cutaneous lesion most closely resembling MASC was found in a neck mass
of a 64-year-old male patient without evidence of a primary salivary gland or
oral tumor. The lesion was excised, and the patient remains disease free to date.
This case depicts a rare tumor in the skin most closely mimicking MASC and brings
additional awareness to dermatopathologists of this tumor.
PMID- 25140658
TI - Retrieval intention modulates the effects of directed forgetting instructions on
recollection.
AB - The neurocognitive basis of memory retrieval is often examined by investigating
brain potential old/new effects, which are differences in brain activity between
successfully remembered repeated stimuli and correctly rejected new stimuli in a
recognition test. In this study, we combined analyses of old/new effects for
words with an item-method directed-forgetting manipulation in order to isolate
differences between the retrieval processes elicited by words that participants
were initially instructed to commit to memory and those that participants were
initially instructed to forget. We compared old/new effects elicited by to-be
forgotten (TBF) words with those elicited by to-be-remembered (TBR) words in both
an explicit-memory test (a recognition test) and an implicit-memory test (a
lexical-decision test). Behavioral results showed clear directed forgetting
effects in the recognition test, but not in the lexical decision test. Mirroring
the behavioral findings, analyses of brain potentials showed evidence of directed
forgetting only in the recognition test. In this test, potentials from 450-650 ms
(P600 old/new effects) were more positive for TBR relative to TBF words. By
contrast, P600 effects evident during the lexical-decision test did not differ in
magnitude between TBR and TBF items. When taken in the context of prior studies
that have linked similar parietal old/new effects to the recollection of episodic
information, these data suggest that directed-forgetting effects manifest
primarily in greater episodic retrieval by TBR than TBF items, and that retrieval
intention may be important for these directed-forgetting effects to occur.
PMID- 25140661
TI - Multiple distinct T-cell clones in folliculotropic mycosis fungoides.
AB - Multiple distinct T-cell clones have been demonstrated in a subset of mycosis
fungoides (MF), but have so far not been documented in folliculotropic MF, a
clinical and histological variant of MF. We analyzed T-cell receptor (TCR) gene
rearrangements in 8 patients with folliculotropic MF with multiple biopsies
(range, 2-5) taken during the course of disease. Two patients had disease stage
IA-IIA, 5 stage IIB-IVA, whereas data were not available for 1 patient. TCR beta
and gamma gene rearrangements were analyzed according to the BIOMED-2 PCR
protocol. Multiple clonal TCR gene rearrangements indicating more than 1 T-cell
clone were found in 5 patients. Although the number of patients is small, the
finding of multiple distinct T-cell clones in 5 out of 8 patients suggests that
chronic T-cell stimulation contributes to the development of folliculotropic MF.
PMID- 25140662
TI - Granuloma Annulare Mimicking Sarcoidosis: Report of Patient With Localized
Granuloma Annulare Whose Skin Lesions Show 3 Clinical Morphologies and 2
Histology Patterns.
AB - Granuloma annulare, a benign dermatosis of undetermined etiology, typically
presents in a localized or generalized form. It has 3 distinctive histologic
patterns: an infiltrative (interstitial) pattern, a palisading granuloma pattern,
and an epithelioid nodule (sarcoidal granuloma) pattern. A man whose granuloma
annulare skin lesions mimicked sarcoidosis is described. His localized granuloma
annulare presented with a total of 3 lesions that each had a distinctive clinical
morphology: an annular lesion of individual papules, a dermal nodule, and a
linear arrangement of 3 papules. Two of his lesions showed a palisading granuloma
histology pattern of granuloma annulare; however, the linear papules on his
posterior neck lesion demonstrated noncaseating granulomas consistent with either
the epithelioid nodule histology pattern of granuloma annulare or sarcoidal
granuloma compatible with sarcoidosis. A comprehensive evaluation excluded the
diagnosis of systemic sarcoidosis. Using the PubMed database, an extensive
literature search was performed on granuloma annulare, epithelioid nodule,
sarcoidal granuloma, and sarcoidosis. The histology patterns of granuloma
annulare-emphasizing the history and differentiating features of the epithelioid
nodule pattern from cutaneous sarcoidosis-were reviewed. The epithelioid nodule
(sarcoidal granuloma) histology pattern of granuloma annulare is uncommon and may
mimic the histology changes observed in sarcoidosis skin lesions; the absence of
asteroid or other giant cell inclusions and an increase in mucin deposition
between the collagen bundles favor the diagnosis of granuloma annulare. In
addition, the epithelioid nodule pattern of granuloma annulare can rarely also
show other histologic patterns of granuloma annulare in the same biopsy specimen
or concurrently present with other clinical lesions of granuloma annulare that
demonstrate a palisading granuloma, or possibly an infiltrative, histology
pattern. However, the presence of an isolated skin lesion demonstrating sarcoidal
granulomas--even when concurrently appearing with other lesions of granuloma
annulare showing either an infiltrative or a palisading granuloma histologic
pattern--may prompt the clinician to evaluate and exclude the possibility of
systemic sarcoidosis.
PMID- 25140663
TI - Solitary Fibrous Tumor With Myxoid Stromal Change.
AB - We report the case of a 46-year-old Korean woman who presented with a 5-month
history of a hyperkeratotic plaque on the left palm. On examination, the plaque
showed an annular pattern with an umbilicated central nodule and a peripheral
palisading induration, which had a verrucous surface. After surgical resection,
histopathologic analysis revealed that the tumor was composed of haphazardly
arranged spindle cells and displayed a predominantly myxoid appearance in the
stroma. The tumor cells were positive for CD34 and bcl-2, but negative for smooth
muscle actin and S-100. The clinical manifestation and histopathologic findings
were most consistent with a diagnosis of solitary fibrous tumor with myxoid
stromal change. There was no evidence of recurrence or metastasis during the 8
month follow-up period. This case highlights the importance of an accurate
diagnosis of solitary fibrous tumors, which may have extensive myxoid stromal
change, hence mimicking other myxoid-type spindle cell tumors.
PMID- 25140664
TI - Congenital melanocytic nevus: two clinicopathological forms.
AB - Congenital melanocytic nevus (CMN) is a hamartomatous disease for which many
attempts at classification have been proposed. This disease is relevant not only
because of its functional and esthetic implications but also because it is a well
documented precursor to malignant melanoma. We performed a clinical and
pathological prospective study of 200 cases of CMN and were able to identify 2
different forms of CMN, each one with biological, clinical, and histopathological
features and criteria that are consistent and repeatable. We propose to name them
types I and II. Type I CMN is the most common, usually, if not always, a single
lesion, it consists of a plaque that involves only 1 anatomic region and does not
go beyond it; type I CNM grows in proportion to the growth of the child, melanoma
rarely develops from it, and when it does it usually arises at the dermoepidermal
junction. Its histopathology shows cords, strands, nests, and single units of
melanocytes spreading between collagen bundles only in the dermis and frequently
the epidermis too, but without trespassing to the hypodermis, that is, it is
superficial. Type II CMN is always made up of many lesions, one of them being
very large and surrounded by many lesions; histopathologically, it involves not
only the skin but also deeper structures, sometimes bone and central nervous
system; therefore, it is deep; when melanoma develops, it does in the dermal
component and usually from the largest plaque. This type of CMN is the one that
develops neurocutaneous melanocytosis. This system is not only easy and logical
but it also has biologic advantages and the clinical-pathological correlation and
criteria are repeatable by clinicians and pathologists.
PMID- 25140666
TI - Cutaneous Pleomorphic Rhabdomyosarcoma Occurring on Sun-Damaged Skin: A Case
Report.
AB - Rhabdomyosarcoma (RMS) is a malignant soft tissue tumor with skeletal muscle
differentiation that can rarely present as a primary cutaneous tumor. There are 3
main subtypes of RMS: embryonal, alveolar, and pleomorphic. Primary cutaneous
pleomorphic RMS is extremely rare, there being only 9 reported cases in the
literature, 2 of which are radiation induced. We present a case of primary
pleomorphic RMS occurring on the sun-damaged skin of the face of an 89-year-old
woman. The tumor was diagnosed by histology, immunohistochemistry, and electron
microscopy. The patient was treated by surgery and adjuvant radiotherapy. The
tumor recurred rapidly after surgical excision. She died 2 months after the
diagnosis from complications of treatment, local symptoms of tumor, and
concurrent illnesses. Primary cutaneous pleomorphic RMS is a rare tumor of adults
and pursues an aggressive clinical course.
PMID- 25140665
TI - Diffuse Reactive Angioendotheliomatosis Secondary to the Administration of
Trabectedin and Pegfilgrastim.
AB - Diffuse dermal angiomatosis is a rare benign condition considered a variant of
reactive angioendotheliomatosis, usually related to vascular disease such as
arteriovenous fistula or severe peripheral vascular disease. The most frequent
clinical manifestations range from a solitary erythematous patch to an indurated
plaque that may ulcerate. A clinical case of a 60-year-old woman who developed
generalized livedoid lesions 2 days after the administration of intravenous
trabectedin and subcutaneous pegfilgrastim for a recidivant myxoid liposarcoma
has been reported. A biopsy of the skin lesions showed a pronounced proliferation
of vessels in the upper dermis that was diagnosed as diffuse dermal angiomatosis.
PMID- 25140667
TI - Langerhans Cell Hyperplasia From Molluscum Contagiosum.
AB - Langerhans cell histiocytosis (LCH) carries a prognosis, which ranges from benign
to potentially fatal. There is currently little framework to decipher metrics,
which predict the benign versus aggressive nature of LCH. We wanted to determine
whether molluscum contagiosum virus (MCV) DNA could be isolated from a cutaneous
lesion, demonstrating Langerhans cell hyperplasia resembling LCH in a patient
with both. Polymerase chain reaction on biopsy-proven MCV and the hyperplastic
lesion has been performed. Two specific regions within the MCV genome were
detected from both biopsies. The authors report our findings and suggest that
some MCV can produce histological lesions resembling LCH, similar to the
literature on scabies mimicking LCH. Efforts to find a reactive "driver" in LCH
may significantly inform the clinical scenario.
PMID- 25140668
TI - Rapid assessment of the coenzyme Q10 redox state using ultrahigh performance
liquid chromatography tandem mass spectrometry.
AB - An improved method for accurate and rapid assessment of the coenzyme Q10 (CoQ10)
redox state using ultrahigh performance liquid chromatography tandem mass
spectrometry was described, with particular attention given to the instability of
the reduced form of CoQ10 during sample preparation, chromatographic separation
and mass spectrometric detection. As highly lipophilic compounds in complex
biological matrices, both reduced and oxidized forms of CoQ10 were extracted
simultaneously from the tissue samples by methanol which is superior to ethanol
and isopropanol. After centrifugation, the supernatants were immediately
separated on a C18 column with isocratic elution using methanol containing 2 mM
ammonium acetate as a non-aqueous mobile phase, and detected by positive
electrospray ionization tandem mass spectrometry in multiple reaction monitoring
(MRM) mode. Ammonium acetate as an additive in methanol provided enhanced mass
spectrometric responses for both forms of CoQ10, primarily due to stable
formation of adduct ions [M + NH4](+), which served as precursor ions in positive
ionization MRM transitions. The assay showed a linear range of 8.6-8585 ng mL(-1)
for CoQ10H2 and 8.6-4292 ng mL(-1) for CoQ10. The limits of detection (LODs) were
7.0 and 1.0 ng mL(-1) and limits of quantification (LOQs) were 15.0 and 5.0 ng
mL(-1) for CoQ10H2 and CoQ10, respectively. This rapid extractive and analytical
method could avoid artificial auto-oxidation of the reduced form of CoQ10,
enabling the native redox state assessment. This reliable method was also
successfully applied for the measurement of the CoQ10 redox state in liver
tissues of mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin, revealing the
down-regulated mitochondrial electron transport chain.
PMID- 25140669
TI - Anterior tooth alignment: A comparison of orthodontic retention regimens 5 years
posttreatment.
AB - OBJECTIVE: To assess orthodontic treatment outcome at debonding and at 3 and 5
years after orthodontic treatment and to investigate the influence of different
retention protocols on anterior tooth alignment. MATERIALS AND METHODS: Using the
Peer Assessment Rating (PAR) Index, 169 patients (74 boys, 95 girls) were
analyzed at four stages: pretreatment (T0), posttreatment (T1), 3 years
posttreatment (T3), and 5 years posttreatment (T5). The PAR anterior component
scores (ACSs) were compared between groups with different retention protocols. In
the maxilla, protocols were removable retainer until T3 (MAX1), removable and
fixed retainer until T3 (MAX2), and removable retainer until T3 and fixed
retainer until T5 (MAX3). In the mandible, protocols were no retainer (MAND1),
fixed 3-3 retainer until T3 (MAND2), and fixed 3-3 retainer until T5 (MAND3).
RESULTS: Mean weighted improvement in PAR score was 88.3% at T1, 86.4% at T3, and
82.1% at T5. The ACS for the maxilla showed no significant differences between
the retention protocols at any time point. In the mandible, the group without
retention showed a gradual but not significant deterioration in ACS throughout
the posttreatment period. At T5 there was a significant difference in ACS between
the group that had the retainer removed at T3 and the group that kept the
retainer. CONCLUSION: The 5-year treatment outcome, as measured by the PAR Index,
was good. Stability of the maxillary anterior alignment 5 years posttreatment did
not appear to be influenced by choice of retention protocol. Mandibular anterior
alignment was significantly better for the group using a fixed retainer compared
with the group where the retainer was removed 3 years posttreatment.
PMID- 25140670
TI - Immunohistochemical expression of CD44 standard and E-cadherin in atypical
leiomyoma and leiomyosarcoma of the uterus.
AB - A family of cell adhesion molecules have been associated with tumorigenesis and
tumour cell invasion. Cadherins and CD44 isoforms are transmembrane
glycoproteins. Uterine smooth muscle tumours range from leiomyomas to
leiomyosarcomas. However, separating malignant from benign can be difficult in a
subset of smooth muscle tumours. Cell adhesion molecules expression may have
diagnostic utility in the distinction of leiomyosarcoma from atypical leiomyoma.
The aim of this study was to evaluate the diagnostic tool role of CD44 standard
and E-cadherin in atypical leiomyoma and leiomyosarcoma. Paraffin blocks of 35
atypical leiomyoma and 22 leiomyosarcoma were analysed immunohistochemically for
the expression CD44 standard and E-cadherin protein. Expression of CD44 standard
was positive in all cases, while E-cadherin was negative. In this study, CD44 and
E-cadherin were not useful for diagnostic tool to differentiate atypical
leiomyoma from leiomyosarcoma.
PMID- 25140671
TI - Base-promoted dehydrogenative coupling of benzene derivatives with amides or
ethers.
AB - Benzene derivatives are introduced into the dehydrogenative coupling via
homolytic aromatic substitution (HAS) as arenes that couple with amides/ethers.
NaOt-Bu is used as a critical promoter of HAS in combination with t-BuOOt-Bu as
an oxidant.
PMID- 25140672
TI - Risk factors of repeated infectious disease incidence among substance-dependent
girls and boys court-referred to treatment.
AB - BACKGROUND: A small portion of Americans account for a disproportionate amount of
the incidences of sexually transmitted infection observed over a short period of
time. Studies with adults have begun to characterize this population, yet there
is very little data on adolescent sexually transmitted infection repeaters
(STIR). This study explores characteristics associated with STIR among 102 girls
and 93 boys (aged 14-18) court-referred for residential treatment. METHODS:
Background characteristics, substance use disorders, risky and interpersonal
behaviors, and history of sexually transmitted infections were collected at
intake using valid and reliable instruments. A negative binomial logistic
regression was performed to determine the background, risky behaviors, and social
patterns associated with adolescent STIR. RESULTS: Approximately two out of three
adolescents (62%) did not use contraception the last time they had sex, and 15%
had at least one sexually transmitted infection recorded in their medical chart.
Sexually transmitted infection repeaters entered treatment with higher rates of
cocaine abuse (13%) than youth without multiple infections (3%, p < 0.05).
History of sexual abuse, having sex with a person who said no, higher
exhibitionism, and social estrangement increased the odds of adolescent STIR.
Main effects of exhibitionism and social estrangement on increased odds of STIR
were more pronounced for sexually abused adolescents. CONCLUSIONS: The findings
suggest a need for incorporating HIV education during residential treatment to
improve health outcomes and intervention strategies that further connectedness
for youth and victims of sexual abuse.
PMID- 25140673
TI - Associations between eating occasion characteristics and age, gender, presence of
children and BMI among U.S. adults.
AB - OBJECTIVE: To describe how frequency and characteristics of traditional meal and
non-meal occasions vary by age, gender, presence of children, and body mass index
(BMI). DESIGN: A cross-sectional survey was administered to a national
demographically balanced sample of adults via an online market research panel.
SETTING: Online survey. SUBJECTS: Survey respondents were in the 18- to 80-year
old age range and had consumed any food or beverage at home or away from home the
previous day. The sample included 2702 adults reporting on 6689 eating/drinking
occasions. Most (80.3%) had no children at home; 43.5% were male and about two
thirds were overweight/obese. MEASURES OF OUTCOME: Eating occasion
characteristics and goals by age, gender, presence of children, and BMI. RESULTS:
Older respondents were more likely to report planning traditional meal occasions
and report on a breakfast occasion than younger respondents. Two prominent
reasons that triggered consumption occasions were habit and hunger/thirst with
one dominant benefit of satisfying hunger or thirst. Habit and nutrition played a
larger role as a goal for eating occasions for older compared to younger
respondents. When children were present in the household, respondents had a goal
of connecting with "family, friends, or colleagues" at dinner compared to those
without children. Few gender differences were noted; however, women more often
reported goals of satisfying hunger/thirst and taste at lunch than men. BMI
levels were related to a range of triggers, goals, and behaviors but not as
prominently as the relationships observed with age. Those with BMI >= 30 were
less health conscious regarding dinner and breakfast consumption compared to
those with a lower BMI. CONCLUSIONS: Among demographic variables, age differences
were noted in relation to eating occasion characteristics more often than other
demographic characteristics or BMI. Understanding these differences can be
beneficial in tailoring promotion of healthful intake at specific eating
occasions for particular subgroups.
PMID- 25140677
TI - Presenting the case for the medical humanities.
PMID- 25140676
TI - Curing and caring competences in the skills training of physiotherapy students.
AB - This article explores the significance of curing and caring competences in
physiotherapy education, as well as how curing and caring competences intersect
within the professional training of physiotherapy students. The empirical data
include participant observations and interviews with students attending skills
training in the first year of a bachelor's degree program in Norway. Curing and
caring are conceptualized as gender-coded competences. That is, curing and caring
are viewed as historical and cultural constructions of masculinities and
femininities within the physiotherapy profession, as well as performative
actions. The findings illuminate the complexity of curing and caring competences
in the skills training of physiotherapy students. Curing and caring are both
binary and intertwined competences; however, whereas binary competences are
mostly concerned with contextual frames, intertwined competences are mostly
concerned with performative aspects. The findings also point to how female and
male students attend to curing and caring competences in similar ways; thus, the
possibilities of transcending traditional gender norms turn out to be significant
in this context. The findings suggest that, although curing somehow remains
hegemonic to caring, the future generation of physiotherapists seemingly will be
able to use their skills for both caring and curing.
PMID- 25140679
TI - A night at the museum--helping residents "see" their patients.
PMID- 25140678
TI - Fostering student engagement in medical humanities courses.
PMID- 25140675
TI - Transcriptomic analysis of tail regeneration in the lizard Anolis carolinensis
reveals activation of conserved vertebrate developmental and repair mechanisms.
AB - Lizards, which are amniote vertebrates like humans, are able to lose and
regenerate a functional tail. Understanding the molecular basis of this process
would advance regenerative approaches in amniotes, including humans. We have
carried out the first transcriptomic analysis of tail regeneration in a lizard,
the green anole Anolis carolinensis, which revealed 326 differentially expressed
genes activating multiple developmental and repair mechanisms. Specifically,
genes involved in wound response, hormonal regulation, musculoskeletal
development, and the Wnt and MAPK/FGF pathways were differentially expressed
along the regenerating tail axis. Furthermore, we identified 2 microRNA precursor
families, 22 unclassified non-coding RNAs, and 3 novel protein-coding genes
significantly enriched in the regenerating tail. However, high levels of
progenitor/stem cell markers were not observed in any region of the regenerating
tail. Furthermore, we observed multiple tissue-type specific clusters of
proliferating cells along the regenerating tail, not localized to the tail tip.
These findings predict a different mechanism of regeneration in the lizard than
the blastema model described in the salamander and the zebrafish, which are
anamniote vertebrates. Thus, lizard tail regrowth involves the activation of
conserved developmental and wound response pathways, which are potential targets
for regenerative medical therapies.
PMID- 25140680
TI - Do future bench researchers need humanities courses in medical school?
PMID- 25140681
TI - Applied medical humanities: addressing vexing deficits, promoting enduring
skills.
PMID- 25140682
TI - FlexMed: a nontraditional admissions program at Icahn School of Medicine at Mount
Sinai.
PMID- 25140683
TI - Creating a space for the arts and humanities at the University of Colorado
Anschutz Medical Campus.
PMID- 25140684
TI - The ethical force of stories: narrative ethics and beyond.
PMID- 25140685
TI - Use of art making in treating older patients with dementia.
PMID- 25140686
TI - Expanding humanities training beyond medical school.
PMID- 25140687
TI - A complete medical education includes the arts and humanities.
PMID- 25140688
TI - Medical ethics and the media: the value of a story.
PMID- 25140689
TI - Music and medicine: harnessing discipline and creativity.
PMID- 25140690
TI - Tangles: an illness narrative in graphic form.
PMID- 25140691
TI - "The best of doctors go to hell": how an ancient talmudic aphorism can inform the
study and practice of medicine.
PMID- 25140692
TI - Intranasal delivery of influenza rNP adjuvanted with c-di-AMP induces strong
humoral and cellular immune responses and provides protection against virus
challenge.
AB - There is a critical need for new influenza vaccines able to protect against
constantly emerging divergent virus strains. This will be sustained by the
induction of vigorous cellular responses and humoral immunity capable of acting
at the portal of entry of this pathogen. In this study we evaluate the protective
efficacy of intranasal vaccination with recombinant influenza nucleoprotein (rNP)
co-administrated with bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di
AMP) as adjuvant. Immunization of BALB/c mice with two doses of the formulation
stimulates high titers of NP-specific IgG in serum and secretory IgA at mucosal
sites. This formulation also promotes a strong Th1 response characterized by high
secretion of INF-gamma and IL-2. The immune response elicited promotes efficient
protection against virus challenge. These results suggest that c-di-AMP is a
potent mucosal adjuvant which may significantly contribute towards the
development of innovative mucosal vaccines against influenza.
PMID- 25140694
TI - Molecular epidemiology and antimicrobial susceptibility profiles of methicillin
resistant Staphylococcus aureus blood culture isolates: results of the Quebec
Provincial Surveillance Programme.
AB - The objectives of this study were to characterize methicillin-resistant
Staphylococcus aureus (MRSA) blood culture isolates and to determine their
relative importance in both nosocomial and community-acquired infections. A total
of 535 MRSA blood culture isolates were analysed. In vitro susceptibility to 14
agents was determined. The genes nuc, mecA and coding for PVL toxin were
identified by PCR. All isolates were characterized by PFGE or spa typing to
assess their genomic relationships. Most MRSA isolates were retrieved from
nosocomial bloodstream infections (474, 89%) and were of the CMRSA2 genotype.
Healthcare-associated (HA)-MRSA bloodstream infections were associated with older
age (70-89 years, P = 0.002) and most often secondary to central line infections
(P = 0.005). Among MRSA strains associated with community-acquired (CA)-MRSA,
28.8% were isolated in intravenous drug users. CA-MRSA genotypes were more
frequently found in young adults (20-39 years, P < 0.0001) with skin/soft tissue
as the primary sources of infection (P = 0.006). CMRSA10 genotype was the
predominant CA-MRSA strain. All MRSA isolates were susceptible to doxycycline,
tigecycline, trimethoprim/sulfamethoxazole and vancomycin. Both the presence of
the genes coding for PVL toxin (89.8%) and susceptibility to clindamycin (86.5%)
were predictive of CA-MRSA genotypes. Whereas in the USA, HA-MRSA have been
replaced by USA300 (CMRSA10) clone as the predominant MRSA strain type in
positive blood cultures from hospitalized patients, this phenomenon has not been
observed in the province of Quebec.
PMID- 25140695
TI - Synergistic effect of viral load and alcohol consumption on the risk of
persistent high-risk human papillomavirus infection.
AB - PURPOSE: This prospective study aimed to examine the combined effect of viral
load and alcohol consumption on the risk of persistent high-risk (HR) human
papillomavirus (HPV) infection. METHODS: Among women undergoing health screening
between 2002 and 2011 at the National Cancer Center, 284 and 122 women with HR
HPV infection and cytological findings of low-grade squamous intraepithelial or
lower-grade lesions were followed up for 1 and 2 years, respectively.
Multivariate logistic regression analysis was performed, and the relative excess
risk due to interaction (RERI) and synergy index (S) were calculated. RESULTS:
Among drinkers, the risks of 1-year (odds ratio [OR] 4.09, 95% confidence
interval [CI] 2.05-8.18) and 2-year persistence (OR 8.08, CI 2.36-27.6) were
significantly higher for high HPV loads than for low HPV loads; this association
was not seen for non-drinkers. The risks for 1-year (OR 4.14, CI 1.89-9.05) and 2
year persistence (OR 6.61, CI 2.09-20.9) were significantly higher in subjects
with a high HPV load who were also drinkers than in those who were non-drinkers.
A high HPV load together with a longer drinking duration or higher alcohol
consumption was associated with increased risks of 1-year (OR 3.07, CI 1.40-6.75
or OR 2.05, CI 0.87-4.83) and 2-year persistence (OR 6.40, CI 1.72-23.8 or OR
4.14, CI 1.18-14.6). The synergistic effect of alcohol consumption and HR-HPV
load was stronger on the risk of 2-year persistence (RERI = 3.26, S = 2.38) than
on the risk of 1-year persistence (RERI = 1.21, S = 1.63). CONCLUSIONS: The
synergistic effect of HR-HPV load and alcohol consumption was associated with the
risk of HR-HPV persistence and was stronger for longer-term HR-HPV infection.
Limiting alcohol consumption might be an important measure to prevent the
development of cervical cancer in women with a high HR-HPV load.
PMID- 25140698
TI - Why the product labeling for low-dose vaginal estrogen should be changed.
PMID- 25140697
TI - Extent of mangrove nursery habitats determines the geographic distribution of a
coral reef fish in a South-Pacific archipelago.
AB - Understanding the drivers of species' geographic distribution has fundamental
implications for the management of biodiversity. For coral reef fishes, mangroves
have long been recognized as important nursery habitats sustaining biodiversity
in the Western Atlantic but there is still debate about their role in the Indo
Pacific. Here, we combined LA-ICP-MS otolith microchemistry, underwater visual
censuses (UVC) and mangrove cartography to estimate the importance of mangroves
for the Indo-Pacific coral reef fish Lutjanus fulviflamma in the archipelago of
New Caledonia. Otolith elemental compositions allowed high discrimination of
mangroves and reefs with 83.8% and 98.7% correct classification, respectively.
Reefs were characterized by higher concentrations of Rb and Sr and mangroves by
higher concentrations of Ba, Cr, Mn and Sn. All adult L. fulviflamma collected on
reefs presented a mangrove signature during their juvenile stage with 85%
inhabiting mangrove for their entire juvenile life (about 1 year). The analysis
of 2942 UVC revealed that the species was absent from isolated islands of the New
Caledonian archipelago where mangroves were absent. Furthermore, strong positive
correlations existed between the abundance of L. fulviflamma and the area of
mangrove (r = 0.84 for occurrence, 0.93 for density and 0.89 for biomass). These
results indicate that mangrove forest is an obligatory juvenile habitat for L.
fulviflamma in New Caledonia and emphasize the potential importance of mangroves
for Indo-Pacific coral reef fishes.
PMID- 25140696
TI - Similar prevalence of low-abundance drug-resistant variants in treatment-naive
patients with genotype 1a and 1b hepatitis C virus infections as determined by
ultradeep pyrosequencing.
AB - BACKGROUND AND OBJECTIVES: Hepatitis C virus (HCV) variants that confer
resistance to direct-acting-antiviral agents (DAA) have been detected by standard
sequencing technology in genotype (G) 1 viruses from DAA-naive patients. It has
recently been shown that virological response rates are higher and breakthrough
rates are lower in G1b infected patients than in G1a infected patients treated
with certain classes of HCV DAAs. It is not known whether this corresponds to a
difference in the composition of G1a and G1b HCV quasispecies in regards to the
proportion of naturally occurring DAA-resistant variants before treatment.
METHODS: We used ultradeep pyrosequencing to determine the prevalence of low
abundance (<25% of the sequence reads) DAA-resistant variants in 191 NS3 and 116
NS5B isolates from 208 DAA-naive G1-infected patients. RESULTS: A total of 3.5
million high-quality reads of >= 200 nucleotides were generated. The median
coverage depth was 4150x and 4470x per NS3 and NS5B amplicon, respectively. Both
G1a and G1b populations showed Shannon entropy distributions, with no difference
between G1a and G1b in NS3 or NS5B region at the nucleotide level. A higher
number of substitutions that confer resistance to protease inhibitors were
observed in G1a isolates (mainly at amino acid 80 of the NS3 region). The
prevalence of amino acid substitutions that confer resistance to NS5B non
nucleoside inhibitors was similar in G1a and G1b isolates. The NS5B S282T
variant, which confers resistance to the polymerase inhibitors mericitabine and
sofosbuvir, was not detected in any sample. CONCLUSION: The quasispecies genetic
diversity and prevalence of DAA-resistant variants was similar in G1a and G1b
isolates and in both NS3 and NS5B regions, suggesting that this is not a
determinant for the higher level of DAA resistance observed across G1a HCV
infected patients upon treatment.
PMID- 25140701
TI - Identification and characterization of phenol hydroxylase from phenol-degrading
Candida tropicalis strain JH8.
AB - The gene phhY encoding phenol hydroxylase from Candida tropicalis JH8 was cloned,
sequenced, and expressed in Escherichia coli. The gene phhY contained an open
reading frame of 2130 bp encoding a polypeptide of 709 amino acid residues. From
its sequence analysis, it is a member of a family of flavin-containing aromatic
hydroxylases and shares 41% amino acid identity with phenol hydroxylase from
Trichosporon cutaneum. The recombinant phenol hydroxylase exists as a
homotetramer structure with a native molecular mass of 320 kDa. Recombinant
phenol hydroxylase was insensitive to pH treatment; its optimum pH was at 7.6.
The optimum temperature for the enzyme was 30 degrees C, and its activity was
rapidly lost at temperatures above 60 degrees C. Under the optimal conditions
with phenol as substrate, the K(m) and V(max) of recombinant phenol hydroxylase
were 0.21 mmol.L(-1) and 0.077 MUmol.L(-1).min(-1), respectively. This is the
first paper presenting the cloning and expression in E. coli of the phenol
hydroxylase gene from C. tropicalis and the characterization of the recombinant
phenol hydroxylase.
PMID- 25140702
TI - Trends in Patterns of Posterior Uveitis and Panuveitis in a Tertiary Institution
in Singapore.
AB - PURPOSE: The study aims to analyze the trends of posterior uveitis and panuveitis
patients seen by a tertiary eye center in Singapore between 2004 and 2012.
METHODS: We conducted a retrospective analysis of 363 consecutive new cases of
posterior uveitis and panuveitis. The cases were segregated into idiopathic,
infectious, or noninfectious. RESULTS: We found statistically significant
differences between etiologies and ethnicity (p = 0.014). We noticed a
statistically significant downward trend (Spearman's rho (rho) = -0.812, p =
0.008) for dengue uveitis, and an upward trend for the idiopathic category
(Spearman's rho (rho) = 0.753, p = 0.019). CONCLUSIONS: We observed differences
between etiologies and ethnicity, pointing toward potential susceptibility
variations. There was an upward trend of idiopathic causes, possibly due to
better control of systemic and infectious etiologies. The dengue uveitis
incidence correlates well with our national statistics. The downward trend of
dengue uveitis could be due to the introduction of Singapore's dengue
surveillance in 2005, emphasizing the importance of controlling the disease.
PMID- 25140699
TI - Morning surge of ventricular arrhythmias in a new arrhythmogenic canine model of
chronic heart failure is associated with attenuation of time-of-day dependence of
heart rate and autonomic adaptation, and reduced cardiac chaos.
AB - Patients with chronic heart failure (CHF) exhibit a morning surge in ventricular
arrhythmias, but the underlying cause remains unknown. The aim of this study was
to determine if heart rate dynamics, autonomic input (assessed by heart rate
variability (HRV)) and nonlinear dynamics as well as their abnormal time-of-day
dependent oscillations in a newly developed arrhythmogenic canine heart failure
model are associated with a morning surge in ventricular arrhythmias. CHF was
induced in dogs by aortic insufficiency & aortic constriction, and assessed by
echocardiography. Holter monitoring was performed to study time-of-day-dependent
variation in ventricular arrhythmias (PVCs, VT), traditional HRV measures, and
nonlinear dynamics (including detrended fluctuations analysis alpha1 and alpha2
(DFAalpha1 & DFAalpha2), correlation dimension (CD), and Shannon entropy (SE)) at
baseline, as well as 240 days (240 d) and 720 days (720 d) following CHF
induction. LV fractional shortening was decreased at both 240 d and 720 d. Both
PVCs and VT increased with CHF duration and showed a morning rise (2.5-fold & 1.8
fold increase at 6 AM-noon vs midnight-6 AM) during CHF. The morning rise in HR
at baseline was significantly attenuated by 52% with development of CHF (at both
240 d & 720 d). Morning rise in the ratio of low frequency to high frequency
(LF/HF) HRV at baseline was markedly attenuated with CHF. DFAalpha1, DFAalpha2,
CD and SE all decreased with CHF by 31, 17, 34 and 7%, respectively. Time-of-day
dependent variations in LF/HF, CD, DFA alpha1 and SE, observed at baseline, were
lost during CHF. Thus in this new arrhythmogenic canine CHF model, attenuated
morning HR rise, blunted autonomic oscillation, decreased cardiac chaos and
complexity of heart rate, as well as aberrant time-of-day-dependent variations in
many of these parameters were associated with a morning surge of ventricular
arrhythmias.
PMID- 25140703
TI - Triaxial transarterial embolization for lower gastrointestinal bleeding: a
retrospective case series.
AB - OBJECTIVE: Superselective transcatheter arterial embolization (TAE) is important
for lower gastrointestinal (GI) bleeding. A new 1.9-Fr. no-taper microcatheter
has recently become available and can be inserted into a 2.7-Fr. microcatheter.
We assessed the applicability of this new triple co-axial (triaxial) system to
TAE for lower GI bleeding. MATERIAL AND METHODS: Five patients with lower GI
bleeding underwent TAE with the triaxial system. The approach was via the femoral
artery with a 4-Fr. sheath in all cases. The 4-Fr. catheter and triaxial system
were inserted into the artery in which extravasation had occurred. Coil
embolization was performed with 0.010-inch coils. We evaluated technical success
rate, clinical success rate and complications. RESULTS: All five cases of
bleeding occurred at the ascending colon, and were caused by diverticulosis in
four cases, and an injury to the artery during polypectomy in one case. The 1.9
Fr. no-taper microcatheter could be inserted into the site of extravasation, the
vasa recta, in all procedures and TAE was performed successfully. The
disappearance of extravasation was confirmed in all cases following TAE. No
patients exhibited any signs of recurrent bleeding or complication. CONCLUSION:
The triaxial system appears to be effective and useful in superselective TAE for
lower GI bleeding.
PMID- 25140704
TI - CRISPR/Cas9-mediated gene knock-down in post-mitotic neurons.
AB - The prokaryotic adaptive immune system CRISPR/Cas9 has recently been adapted for
genome editing in eukaryotic cells. This technique allows for sequence-specific
induction of double-strand breaks in genomic DNA of individual cells, effectively
resulting in knock-out of targeted genes. It thus promises to be an ideal
candidate for application in neuroscience where constitutive genetic
modifications are frequently either lethal or ineffective due to adaptive changes
of the brain. Here we use CRISPR/Cas9 to knock-out Grin1, the gene encoding the
obligatory NMDA receptor subunit protein GluN1, in a sparse population of mouse
pyramidal neurons. Within this genetically mosaic tissue, manipulated cells lack
synaptic current mediated by NMDA-type glutamate receptors consistent with
complete knock-out of the targeted gene. Our results show the first proof-of
principle demonstration of CRISPR/Cas9-mediated knock-down in neurons in vivo,
where it can be a useful tool to study the function of specific proteins in
neuronal circuits.
PMID- 25140706
TI - Belatacept-based immunosuppression in a chagasic adult recipient of en bloc
pediatric kidneys.
PMID- 25140705
TI - The neural bases of directed and spontaneous mental state attributions to group
agents.
AB - In daily life, perceivers often need to predict and interpret the behavior of
group agents, such as corporations and governments. Although research has
investigated how perceivers reason about individual members of particular groups,
less is known about how perceivers reason about group agents themselves. The
present studies investigate how perceivers understand group agents by
investigating the extent to which understanding the 'mind' of the group as a
whole shares important properties and processes with understanding the minds of
individuals. Experiment 1 demonstrates that perceivers are sometimes willing to
attribute a mental state to a group as a whole even when they are not willing to
attribute that mental state to any of the individual members of the group,
suggesting that perceivers can reason about the beliefs and desires of group
agents over and above those of their individual members. Experiment 2
demonstrates that the degree of activation in brain regions associated with
attributing mental states to individuals--i.e., brain regions associated with
mentalizing or theory-of-mind, including the medial prefrontal cortex (MPFC),
temporo-parietal junction (TPJ), and precuneus--does not distinguish individual
from group targets, either when reading statements about those targets' mental
states (directed) or when attributing mental states implicitly in order to
predict their behavior (spontaneous). Together, these results help to illuminate
the processes that support understanding group agents themselves.
PMID- 25140707
TI - Benevolent characteristics promote cooperative behaviour among humans.
AB - Cooperation is fundamental to the evolution of human society. We regularly
observe cooperative behaviour in everyday life and in controlled experiments with
anonymous people, even though standard economic models predict that they should
deviate from the collective interest and act so as to maximise their own
individual payoff. However, there is typically heterogeneity across subjects:
some may cooperate, while others may not. Since individual factors promoting
cooperation could be used by institutions to indirectly prime cooperation, this
heterogeneity raises the important question of who these cooperators are. We have
conducted a series of experiments to study whether benevolence, defined as a
unilateral act of paying a cost to increase the welfare of someone else beyond
one's own, is related to cooperation in a subsequent one-shot anonymous
Prisoner's dilemma. Contrary to the predictions of the widely used inequity
aversion models, we find that benevolence does exist and a large majority of
people behave this way. We also find benevolence to be correlated with
cooperative behaviour. Finally, we show a causal link between benevolence and
cooperation: priming people to think positively about benevolent behaviour makes
them significantly more cooperative than priming them to think malevolently. Thus
benevolent people exist and cooperate more.
PMID- 25140710
TI - Relationship between periodontal disease and obesity: the role of life-course
events.
AB - Periodontal disease is ranked among the 10 most prevalent chronic diseases
worldwide, and is considered a major public health problem. Its etiology has been
associated with local and general conditions that could interfere in the host
immune response. Obesity, like periodontal disease, has emerged as a prevalent
chronic disease in high-, low- and medium-income countries, recognized as risk
factor for cardiovascular disease and cancer. A relationship between periodontal
health and obesity may exist, but the mechanism that would explain this
association remains unclear. Life-course epidemiology could be a useful
instrument to investigate a casual association between early exposures and later
outcomes, being appropriate for understanding the establishment of chronic
conditions. This approach comprehends different theories, considering the time,
the duration and the intensity of early exposition, and its impact on the
development of chronic diseases in later life. Thus, the aim of this study is to
hypothesize the different life-course epidemiology theories to explain the
possible association between periodontal health and nutritional status in
adulthood.
PMID- 25140709
TI - Prevalence and trends in obesity among China's children and adolescents, 1985
2010.
AB - OBJECTIVES: We examined the prevalence of and trends in obesity among children
and adolescents in China (1985-2010). METHODS: We used data from the 1985, 1991,
1995, 2000, 2005, and 2010 Chinese National Surveys on Students' Constitution and
Health (CNSSCH). The CNSSCH is a national survey of physical fitness and health
status in Chinese students that uses multistage stratified sampling of 31
provinces and municipalities. A subject was considered obese or overweight if
weight-for-height exceeded the 20% or 10% of standard weight-for-height. The
standard weight-for-height was the 80th percentile for sex- and age-specific
growth charts. RESULTS: The age-adjusted prevalence of obesity and of overweight
and obesity combined was 8.1% (95% CI, 8.0-8.3%) and 19.2% (95% CI, 19.1-19.4%)
among children and adolescents 7-18 years in age. Obesity was more likely to be
present among children or adolescents who were male (RR, 1.93; 95% CI, 1.90
1.97), urban (RR, 1.99; 95% CI, 1.95-2.02), or 10-12 years (RR, 1.43; 95% CI,
1.40-1.46). Trend analyses of the 25-year period revealed a significant
increasing trend in males (RR, 1.59; 95% CI, 1.58-1.60) and in females (RR, 1.49;
95% CI, 1.48-1.50). The rate of increase in obese or overweight prevalence was
highest in boys from rural areas (9% annual increase). CONCLUSIONS: During 1985
2010, there was a significant and continuous increase in the prevalence of
obesity in children and adolescents. Obesity is epidemic in China, but may be
reduced with evidence-based interventions (e.g., school intervention programs).
PMID- 25140711
TI - Effects of nonsurgical periodontal treatment on the alveolar bone density.
AB - The aim of this study was to evaluate the effects of nonsurgical periodontal
treatment on alveolar bone density (ABD) and bone height (BH) using direct
digital radiography. Nineteen patients (mean age: 36 +/- 7.3 years) with
generalized chronic periodontitis were examined at baseline, 90 (90 AT) and 180
(180 AT) days after nonsurgical periodontal therapy. Radiographs were taken from
two sites with specific characteristics: 39 sites with probing pocket depth (PPD)
<= 3 mm and clinical attachment level (CAL) <= 1 mm (shallow sites); and 62 sites
with PPD >= 5 mm and CAL >= 3 mm (deep sites). The ABD was assessed considering
the bone regions of interest at the alveolar bone crest (ROI I) and at the
medullar bone (ROI II). The BH was assessed considering the distance from the
alveolar bone crest to the cementoenamel junction. Mann-Whitney test was used for
the overall demographic data, Wilcoxon test was used to compare the baseline, 90
AT and 180 AT data as well as to compare the groups and subgroups within the same
evaluation period. The significance level was set at 5%. The deep sites showed a
significant increase of ABD in ROI I at 90 AT (p<0.007) and at 180 AT (p<0.005).
ABD decrease was seen in ROI II at 180 AT (p<0.04) while BH reduced only in
shallow sites at 90 AT. In conclusion, an increase in ABD was observed in deep
sites of patients with generalized chronic periodontitis. However, no significant
change in alveolar BH was observed in these sites.
PMID- 25140712
TI - Effects of titanium surfaces on the developmental profile of
monocytes/macrophages.
AB - Due to the critical role of monocytes/macrophages (Mphi) in bone healing, this
study evaluated the effects of bio-anodized, acid-etched, and machined titanium
surfaces (Ti) on Mphi behavior. Cells were separated from whole human blood from
10 patients, plated on Ti or polystyrene (control) surfaces, and cultured for 72
h. At 24, 48 and 72 h, cell viability, levels of IL1beta, IL10, TNFalpha,
TGFbeta1 inflammatory mediators, and nitric oxide (NO) release were analyzed by
mitochondrial colorimetric assay (MTT assay) and immunoenzymatic assays,
respectively. Real-time PCR was used to verify the expression of TNFalpha and
IL10 at 72 h. The data were subjected to a Kruskal-Wallis analysis. IL1beta,
TNFalpha and TGFbeta1 release were not significantly different between the Ti
surfaces (p>0.05). The presence of NO and IL10 was not detected in the samples.
Cell viability did not differ between the samples cultivated on Ti and those
cultivated on control surfaces, except at 24 h (p=0.0033). With respect to the
mediators evaluated, the surface characteristics did not induce a typical Th1 or
Th2 cytokine profile, although the cell morphology and topography were influenced
by the Ti surface during the initial period.
PMID- 25140713
TI - Biocompatibility of a calcium hydroxide-propolis experimental paste in rat
subcutaneous tissue.
AB - Intracanal medications are fundamental for disinfection of the root canal system
and participate in periapical repair, so their biocompatibility is of utmost
importance to avoid tissue damage. This study evaluated the biocompatibility of a
experimental paste of calcium hydroxide and propolis in the subcutaneous tissue
of rats. The study was conducted on 15 male Wistar rats. Two incisions were made
on the dorsal region of each animal for introduction of 4 tubes: one tube was
empty; one contained zinc oxide-eugenol cement, and the two other tubes were
filled with experimental paste. After 7, 14 and 30 days, the animals were
euthanized and the specimens were subjected to histotechnical preparation. The
hematoxylin and eosin-stained histological sections were analyzed by light
microscopy. Scores were established according to the inflammatory process and
statistically compared by the Tukey test (alpha = 5%). The analysis of
histological sections showed non-significant or mild inflammatory reaction in the
connective tissue in contact with the empty tubes in all study periods while the
contact of subcutaneous tissue with zinc oxide-eugenol elicited moderate or
severe inflammation similarly without significant difference among the study
periods. The connective tissue was moderately inflamed at 7 days when contacting
the experimental paste, but the inflammatory process was non-significant or mild
at 14 and 30 days. The experimental paste was biocompatible with the tissues
after 14 days of subcutaneous implantation.
PMID- 25140714
TI - Detection of organochlorine compounds formed during the contact of sodium
hypochlorite with dentin and dental pulp.
AB - This study used gas chromatography-mass spectrometry (GC-MS) to detect the
products formed during the contact of sodium hypochlorite (NaOCl) with bovine
pulp and dentin. For analysis of the products formed in the volatile phase, 11 mg
of bovine pulp tissue were placed in contact with 0.5%, 2.5% and 5.25% NaOCl
until complete tissue dissolution occurred. The solid phase microextraction
(SPME) fiber was exposed inside the container through the cover membrane and
immediately injected into the GC-MS system. 30 mg of the of dentin were kept in
contact with NaOCl, and then the SPME fiber was exposed inside the container
through the cover membrane for adsorption of the products and injected into the
GC-MS system. The same protocol was used for the aqueous phase. For analysis of
the volatile compounds, the final solution was extracted using pure ethyl ether.
The suspended particulate phase of the mixture was aspirated, and ether was
separated from the aqueous phase of the solution. The ether containing the
products that resulted from the chemical interaction of dentin and pulp with the
NaOCl was filtered and then injected into the GC-MS system for analysis of the
aqueous phase. The aqueous and volatile phases of both dentin and pulp showed the
formation of chloroform, hexachloroethane, dichloromethylbenzene and
benzaldehyde. In conclusion, organochlorine compounds are generated during the
contact of dentin and pulp with NaOCl at concentrations of 0.5%, 2.5% and 5.25%.
PMID- 25140715
TI - Influence of sealer placement technique on the quality of root canal filling by
lateral compaction or single cone.
AB - The aim of this study was to evaluate the influence of the sealer placement
technique on the quality of root canal filling using Lateral Compaction (LC) or
Single Cone (SC). In order to do that, 60 mesial roots of mandibular first molars
were prepared and divided into 2 groups (n=30), according to the filling
technique: LC and SC. Each group was subdivided into 3 subgroups (n=10),
according to the different sealer placement methods: A: Master gutta-percha (GP)
cone; B: Lentulo spiral; C: File. The roots were sectioned at 2, 4 and 6 mm from
the apex and photographed with the aid of a digital microscope. Then, areas of
GP, endodontic sealer and voids were measured, and these data were subjected to
statistical analysis. LC technique showed no statistically difference (p>0.05) in
the percentage of GP area, sealer and voids between the subgroups at any of the
three levels. After use of SC, higher percentages of sealer area were found at
all levels (p<0.01) when the sealer was placed with a file. At 2 mm, higher
percentage of void areas (p<0.05) was observed when the cone was used, lower
percentage with K-file and the lowest percentage with Lentulo. At 4 mm, cone
showed higher percentage of void areas (p<0.05). At 6 mm, there were no
significant differences (p>0.05) between the three methods. Considering these
results, using an instrument for sealer placement was important in the SC
technique to reduce voids. Regarding LC, the sealer placement techniques provided
similar results.
PMID- 25140716
TI - Periapical status and prevalence of endodontic treatment in institutionalized
elderly.
AB - The aim of this study was to determine the prevalence and frequency of apical
periodontitis and root fillings in 450 institutionalized Brazilian elderly. The
teeth with apical periodontitis were assessed using the Periapical Index (PAI)
score. A total of 942 teeth were evaluated in 98 subjects (57 females and 41
males) with mean age of 74 years. The observed frequency of total edentulous
subjects was high (76%) in this population. A total of 126 teeth showed root
fillings, of these only 46 (36.5%) were scored as having adequate quality. Apical
periodontitis was found in 114 teeth (12.1%) in 42 (42.9%) subjects. 80 (70.2%)
inadequate root-filled teeth showed apical periodontitis. There was a significant
correlation between the presence of periapical pathology and inadequate root
filled teeth. Inadequate root-filled teeth were associated with an increased
prevalence of apical periodontitis in these subjects. This fact may result in
increased endodontic retreatment needs for this population.
PMID- 25140717
TI - Canal preparation and filling techniques do not influence the fracture resistance
of extensively damaged teeth.
AB - The purpose of this study was to assess the fracture resistance of extensively
damaged teeth after two root canal preparation techniques (hand and rotary files)
and after two filling techniques (active and passive compaction). Sixty-eight
maxillary canines roots with an apical diameter equal to that of a #25 K-file
were embedded in acrylic resin and the periodontal ligament was simulated by
using a polyether impression material. The roots were randomly distributed into
four groups (n=17): hand preparation and active compaction (HA), hand preparation
and passive compaction (HP), rotary preparation and active compaction (RA), and
rotary preparation and passive compaction (RP). All roots were restored with
glass fiber post and metallic crown. The specimens were mechanically cycled
(500,000 cycles, 45 degrees , 37 degrees C, 133 N, 2 Hz) and then subjected to
a fracture resistanhe fracture resistance values ranged between 621.15 N (HP) and
785.71 N (HA). However, the Kruskal-Wallis test did not reveal differences in the
fracture ce test. A single blinded examiner analyzed the external root surface
and classified the failure pattern as favorable or unfavorable. Tresistance
values among the four groups (p =0.247). Under the tested conditions, root canal
preparation and filling techniques had no influence on the fracture resistance of
extensively damaged teeth restored with fiber post and metallic crown.
PMID- 25140718
TI - In vitro tensile strength of luting cements on metallic substrate.
AB - The aim of this study was to determine the tensile strength of crowns cemented on
metallic substrate with four different types of luting agents. Twenty human
maxillary molars with similar diameters were selected and prepared to receive
metallic core castings (Cu-Al). After cementation and preparation the cores were
measured and the area of crown's portion was calculated. The teeth were divided
into four groups based on the luting agent used to cement the crowns: zinc
phosphate cement; glass ionomer cement; resin cement Rely X; and resin cement
Panavia F. The teeth with the crowns cemented were subjected to thermocycling and
later to the tensile strength test using universal testing machine with a load
cell of 200 kgf and a crosshead speed of 0.5 mm/min. The load required to
dislodge the crowns was recorded and converted to MPa/mm(2). Data were subjected
to Kruskal-Wallis analysis with a significance level of 1%. Panavia F showed
significantly higher retention in core casts (3.067 MPa/mm(2)), when compared
with the other cements. Rely X showed a mean retention value of 1.877 MPa/mm(2)
and the zinc phosphate cement with 1.155 MPa/mm(2). Glass ionomer cement (0.884
MPa/mm(2)) exhibited the lowest tensile strength value. Crowns cemented with
Panavia F on cast metallic posts and cores presented higher tensile strength. The
glass ionomer cement showed the lowest tensile strength among all the cements
studied.
PMID- 25140719
TI - Addition of silver nanoparticles to composite resin: effect on physical and
bactericidal properties in vitro.
AB - The objectives of this study were to evaluate physical properties and
antibacterial activity of a light-activated composite modified with silver
nanoparticles. Discs were produced with unmodified resin (control group - CG) and
modified resin with silver nanoparticles at two concentrations, 0.3% wt (MR03)
and 0.6% wt (MR06). Streptococcus mutans and Lactobacillus acidophilus biofilms
were induced in vitro by incubation of discs in a 20% sucrose medium, followed by
sonication and counting of viable cells after 1, 4 and 7 days (n=9). The
arithmetic roughness of all three groups was evaluated by atomic force microscopy
(n=9). Compression assay was conducted in all groups to measure the compressive
strength at failure and elasticity modulus (n=5). Data were subjected to ANOVA
and Tukey's tests (alpha=0.05%). At all three time points the number of viable
cells was statistically lower for MR03 and MR06 compared with CG, for both
specimens. MR03 and MR06 showed no significant differences. Microscopic analysis
demonstrated no significant differences for roughness among the three groups
(p>0.05). The MR03 was stronger to compression than CG, and MR06 was
statistically lower than CG and MR03. It was concluded that the MR03 were less
conducive to biofilm growth, without compromising the strength in compression and
surface roughness.
PMID- 25140720
TI - Assessment of tooth structure using an alternative electrical bioimpedance
spectroscopy method.
AB - In the past few years bioimpedance has been used in many applications in
dentistry, such as estimating the length of root canals and the physical
properties of enamel. Despite the significant number of studies using
bioimpedance to investigate the dental structure, many of them use only the real
component of bioimpedance, i.e., the resistance, disregarding the information
provided by the imaginary one, i.e., the reactance. Moreover, in different
studies that investigate both parts of bioimpedance, the data are obtained by
using single frequency or multifrequency methods based on sinusoidal sweep. The
aim of this study was to investigate the use of an alternative bioimpedance
spectroscopy (BIS) method based on step response in the assessment of tooth
structure. To test the feasibility of the studied method we performed in vitro
experiments that considered the successive removal of enamel layers of 22 healthy
teeth, the accomplishment of the BIS method, and the estimate of bioimpedance
parameter that were associated with the changes in the tooth structure. To deal
with the variability of bioimpedance parameters a dental health index (DHI) is
proposed. The findings include the behavior of bioimpedance parameters of intact
teeth, as well as those associated with the successive removal of the enamel
layer, and indicate that DHI is sensitive enough to detect changes of the enamel
layer. The results point to the feasibility of the studied BIS method in
evaluating tooth structure and that it might be used to assess dental health.
PMID- 25140721
TI - Characterization of dentifrices containing desensitizing agents, triclosan or
whitening agents: EDX and SEM analysis.
AB - Dentifrices with different compositions are available on the market, but there is
limited information about their properties. The aim of this in vitro study was to
evaluate the physicochemical characteristics of 12 dentifrices divided into three
categories, as containing desensitizing agents, Triclosan or whitening agents.
Desiccation loss/residue analysis: 5 g of dentifrice was weighed five times for
each group. pH analysis: 5 g of dentifrice were diluted in three parts of
distilled water and analyzed using a digital potentiometer. Scanning electron
microscopy (SEM): analysis of ashes, shape and size of the particles. Energy
dispersive x-ray spectroscopy (EDX): identification of the abrasive elements.
Data were analyzed using ANOVA, Bonferroni post hoc test (alpha=0.05).
Desiccation loss: 38.21% to 65.83%. Dentifrices containing Triclosan and
desensitizing agents showed statistically significant differences among them
(p<0.05). Whitening dentifrices showed statistically significant differences
between Close-Up Whitening and Sensodyne Branqueador (44.72%, 65.83%,
respectively). Most dentifrices presented neutral or basic pH. Different shape
and size particles were observed in the SEM analysis. Abrasive elements were
identified in the EDX. These results demonstrate that the evaluated dentifrices
had different properties and their composition influences directly their
characteristics, thus resulting in a more or less abrasive action on tooth
surface. Knowing the characteristics of the dentifrices is important to indicate
the ideal product for each case.
PMID- 25140722
TI - Insoluble NaF in Duraphat(r) may prolong fluoride reactivity of varnish retained
on dental surfaces.
AB - There is no consensus about the clinical recommendation of the time that
Duraphat(r) varnish should be maintained on enamel surfaces without suffering
mechanical disturbance by the patient. Considering the importance of calcium
fluoride (CaF2)-like reservoirs on the anticaries effect of professional fluoride
application, an in vitro study was designed to test the reactivity of Duraphat(r)
varnish with enamel forming these reservoirs as a function of time. Since most
fluoride in Duraphat(r) varnish is insoluble to react and form products on
enamel, the relative contribution of the varnish soluble and insoluble fluoride
fractions to the reactivity was also evaluated. For this, whole-varnish,
containing soluble and insoluble fluoride (total fluoride concentration of 23699
+/- 384 ug F/g), or centrifuged varnish, containing only soluble fluoride
(fluoride concentration of 258 +/- 97 ug F/g), were applied in a standardized
manner on enamel slabs (n=8/varnish group/time), which were immersed in
continuously renewed artificial saliva for up to 36 h. CaF2-like reservoirs
formed on enamel by varnish application were extracted using 1 M KOH and fluoride
concentration was measured with ion specific electrode. The results were
expressed as ug F/cm(2) of enamel area. Whole varnish formed significantly higher
fluoride concentration on enamel than centrifuged varnish, reaching maximum
concentration at 24 h (22.0 +/- 4.5 ug F/cm(2)). Centrifuged varnish reached
maximum concentration at 6 h (3.20 +/- 0.81 ug F/cm(2)). In conclusion, a longer
varnish retention time than the usually recommended could improve the anticaries
effect of Duraphat(r) varnish, allowing that NaF particles, initially insoluble
in the varnish matrix, prolong the reactivity with enamel.
PMID- 25140723
TI - Antimicrobial activity and synergism of lactoferrin and lysozyme against
cariogenic microorganisms.
AB - The present study evaluated the antimicrobial in vitro effects of the salivary
proteins lactoferrin and lysozyme on microorganisms involved in the carious
process, obtaining their minimum inhibitory concentration (MIC) and minimum
bactericidal concentration (MBC). Streptococcus mutans (ATCC 25175) and
Lactobacillus casei (ATCC 7469) were submitted to broth macrodilution of lysozyme
at 80 mg/mL and lactoferrin at 200 mg/mL. The tubes were read in a
spectrophotometer after they had been incubated at 37 degrees C for 18 h, in a
carbon dioxide chamber, in order to read the MIC. A new subculture was carried on
agar plates to obtain the MBC. The agar diffusion method was also tested, using
BHI agar with 100 uL of the standardized microbial inocula. Filter-paper disks
soaked in 10 uL of the solutions lactoferrin (200 ug/mL) and lysozyme (80 ug/mL)
were placed on the agar surface. Inhibition halos were not observed on the
plates, showing the absence of the antimicrobial effects of these proteins in
this method. The bactericidal and bacteriostatic effects of lysozyme on L. casei
were 50.3 mg/mL and 43.1 mg/mL respectively. The bactericidal and bacteriostatic
effects on S. mutans were 68.5 mg/mL and 58.7 mg/mL. Lactoferrin did not induce
any inhibitory effects on any microorganism, even in the concentration of 200
mg/mL. There was not a synergic antimicrobial effect of proteins, when they were
tested together, even in the concentration of 42.8 mg/mL of lysozyme and 114
mg/mL of lactoferrin (the highest values evaluated). S. mutans and L. casei were
only inhibited by lysozyme, not affected by lactoferrin and by the synergic use
of both proteins.
PMID- 25140724
TI - Anteroposterior and vertical changes in skeletal class II patients treated with
modified Thurow appliance.
AB - The aim of this study was to evaluate the post-treatment anteroposterior and
vertical alterations in skeletal Class II malocclusion with different maxillary
patterns in patients treated with modified Thurow appliance. Forty-five patients
(22 girls and 23 boys) with skeletal Class II and angle SN.GoGn <= 35 and
different maxillary patterns (n = 15), as follows: retrusive (SNA<80 degrees ),
normal (SNA = 80 degrees - 84 degrees ) or protrusive (SNA>84 degrees ) maxilla;
mean age 9 years at pre-treatment (T1) and 9 years and 10 months at post
treatment (T2), were treated with modified Thurow cervical traction appliance,
with expander screw and extraoral face bow with 10 degrees to 20 degrees fold
in relation to the intraoral arch. Force of 500 gf was applied and use for 12 to
14 h/day, with fortnightly adjustments. Analysis of variance ANOVA followed by
post-hoc Tukey and Kruskal-Wallis test, followed by Mann-Whitney were used (alpha
= 5%). In changes obtained from stage T1 to T2, no statistically significant
differences were found among the groups Protrusive, normal and retrusive maxilla
for the variables SNB, SN.GoGn, 1.NA, overjet, overbite and Class II discrepancy
(right and left) (p>0.05). Angular measurements SNA and ANB in the protrusive
maxilla group were significantly greater than in the normal and retrusive maxilla
groups (p<0.01). However, in the normal maxilla group these values did not differ
significantly from those of the retrusive maxilla group (p>0.05). Within the
limits of this study, it may be concluded that the modified Thurow cervical
traction appliance was efficient for the correction of skeletal Class II
irrespective of the maxillary pattern. The mandible had no significant rotation
during treatment.
PMID- 25140726
TI - F, Ca co-doped TiO2 nanocrystals with enhanced photocatalytic activity.
AB - F, Ca co-doped TiO2 was synthesized by a facile one-step hydrothermal method.
After doping with F, electrons can be simultaneously excited from valence band to
the F doping energy level. The smaller crystal size caused by doping with Ca can
exhibit more powerful redox ability and the efficient separation of
photogenerated hole-electron pairs. Therefore, F, Ca co-doped TiO2 exhibited
enhanced photocatalytic activity.
PMID- 25140725
TI - Germ cell nuclear factor regulates gametogenesis in developing gonads.
AB - Expression of germ cell nuclear factor (GCNF; Nr6a1), an orphan member of the
nuclear receptor gene family of transcription factors, during gastrulation and
neurulation is critical for normal embryogenesis in mice. Gcnf represses the
expression of the POU-domain transcription factor Oct4 (Pou5f1) during mouse post
implantation development. Although Gcnf expression is not critical for the
embryonic segregation of the germ cell lineage, we found that sexually dimorphic
expression of Gcnf in germ cells correlates with the expression of pluripotency
associated genes, such as Oct4, Sox2, and Nanog, as well as the early meiotic
marker gene Stra8. To elucidate the role of Gcnf during mouse germ cell
differentiation, we generated an ex vivo Gcnf-knockdown model in combination with
a regulated CreLox mutation of Gcnf. Lack of Gcnf impairs normal spermatogenesis
and oogenesis in vivo, as well as the derivation of germ cells from embryonic
stem cells (ESCs) in vitro. Inactivation of the Gcnf gene in vivo leads to loss
of repression of Oct4 expression in both male and female gonads.
PMID- 25140728
TI - Asymmetric domino reaction of cyclic N-sulfonylimines and simple aldehydes with
trans-perhydroindolic acid as an organocatalyst.
AB - An asymmetric domino reaction was developed utilizing readily available cyclic N
sulfonylimines and simple aldehydes to construct biologically important and
synthetically challenging piperidine derivatives consisting of three contiguous
stereocenters. trans-Perhydroindolic acid proved to be an efficient
organocatalyst in this reaction (up to 89% yield, 80:20 dr, and 99% ee). The
absolute configuration of the catalytic product was determined by X-ray
crystallography studies. The product could be conveniently converted to
synthetically useful intermediates, such as (3R,4S)-4-ethyl-3-methyl-6
phenylpiperidinyridin-2-one (8), via a simple transformation.
PMID- 25140729
TI - Assessing the combinatorial potential of the RiPP cyanobactin tru pathway.
AB - Ribosomally produced natural products, the RiPPs, exhibit features that are
potentially useful in the creation of large chemical libraries using simple
mutagenesis. RiPPs are encoded on ribosomal precursor peptides, but they are
extensively posttranslationally modified, endowing them with properties that are
useful in drug discovery and biotechnology. In order to determine which mutations
are acceptable, strategies are required to determine sequence selectivity
independently of the context of flanking amino acids. Here, we examined the
absolute sequence selectivity of the trunkamide cyanobactin pathway, tru. A
series of random double and quadruple simultaneous mutants were synthesized and
produced in Escherichia coli. Out of a total of 763 mutated amino acids examined
in 325 unique sequences, 323 amino acids were successfully incorporated in 159
sequences, leading to >300 new compounds. Rules for tru sequence selectivity were
determined, which will be useful for the design and synthesis of combinatorial
biosynthetic libraries. The results are also interpreted in comparison to the
known natural products of tru and pat cyanobactin pathways.
PMID- 25140731
TI - Properties of lignin, cellulose, and hemicelluloses isolated from olive cake and
olive stones: binding of water, oil, bile acids, and glucose.
AB - A process based on a steam explosion pretreatment and alkali solution post
treatment was applied to fractionate olive stones (whole and fragmented, without
seeds) and olive cake into their main constitutive polymers of cellulose (C),
hemicelluloses (H), and lignin (L) under optimal conditions for each fraction
according to earlier works. The chemical characterization (chromatographic method
and UV and IR spectroscopy) and the functional properties (water- and oil-holding
capacities, bile acid binding, and glucose retardation index) of each fraction
were analyzed. The in vitro studies showed a substantial bile acid binding
activity in the fraction containing lignin from olive stones (L) and the alkaline
extractable fraction from olive cake (Lp). Lignin bound significantly more bile
acid than any other fraction and an amount similar to that bound by
cholestyramine (a cholesterol-lowering, bile acid-binding drug), especially when
cholic acid (CA) was tested. These results highlight the health-promoting
potential of lignin from olive stones and olive cake extracted from olive
byproducts.
PMID- 25140732
TI - Plasmonic imaging of electrochemical oxidation of single nanoparticles.
AB - Measuring electrochemical activities of nanomaterials is critical for creating
novel catalysts, for developing ultrasensitive sensors, and for understanding
fundamental nanoelectrochemistry. However, traditional electrochemical methods
measure a large number of nanoparticles, which wash out the properties of
individual nanoparticles. We report here a study of transient electrochemical
oxidation of single Ag nanoparticles during collision with an electrode and
voltammetry of single nanoparticles immobilized on the electrode using a
plasmonic-based electrochemical current microscopy. This technique images both
electrochemical reaction and size of the same individual nanoparticle, enabling
quantitative examination of size-dependent electrochemical activities at single
nanoparticle level. The imaging capability further allows detection of the
reaction kinetics of each individual nanoparticle and analysis of the average
behaviors of multiple nanoparticles. The average kinetics and size dependence can
be accurately described by the Tafel equation, but there is a large variability
between different nanoparticles, which underscores the importance of single
nanoparticle analysis.
PMID- 25140733
TI - Carba-closo-dodecaborate anions with two functional groups: [1-R-12-HC=C-closo-1
CB11H10]- (R = CN, NC, CO2H, C(O)NH2, NHC(O)H).
AB - Disubstituted carba-closo-dodecaborate anions with one functional group bonded to
the cluster carbon atom and one ethynyl group bonded to the antipodal boron atom
were synthesized from easily accessible {closo-1-CB11} clusters. [Et4N][1-NC-12
HC=C-closo-1-CB11H10] ([Et4N]4b) was prepared starting from Cs[12-Et3SiC=C-closo
1-CB11H11] (Cs1c) via salts of the anions [1-HO(O)C-12-HC=C-closo-1-CB11H10](-)
(2b) and [1-H2N(O)C-12-HC=C-closo-1-CB11H10](-) (3b). In a similar reaction
sequence [Et4N][1-CN-12-HC=C-closo-1-CB11H10] ([Et4N]7b) was obtained from Cs[1
H2N-12-HC=C-closo-1-CB11H10] (Cs5b) by formamidation to yield [Et4N][1-H(O)CHN-12
HC=C-closo-1-CB11H10] ([Et4N]6b) and successive dehydration. In addition, the
synthesis of the isonitrile [Et4N][1-CN-closo-1-CB11H11] ([Et4N]7a) is presented.
The {closo-1-CB11} derivatives were characterized by multinuclear NMR as well as
vibrational spectroscopy, mass spectrometry, and elemental analysis. The crystal
structures of [Et4N][1-HO(O)C-12-HC=C-closo-1-CB11H10] ([Et4N]2b), [Et4N][1
H2N(O)C-12-HC=C-closo-1-CB11H10] ([Et4N]3b), [Et4N][1-NC-12-HC=C-closo-1-CB11H10]
([Et4N]4b), [Et4N][1-H(O)CHN-12-HC=C-closo-1-CB11H10] ([Et4N]6b), [Et4N][1-CN-12
HC=C-closo-1-CB11H10] ([Et4N]7b), and K[1-H(O)CHN-closo-1-CB11H11] ([Et4N]6a)
were determined. The transmission of electronic effects through the carba-closo
dodecaboron cage was studied based on (13)C NMR spectroscopic data, by results
derived from density functional theory calculations, and by a comparison to the
data of related benzene and bicyclo[2.2.2]octane derivatives.
PMID- 25140734
TI - Enhancement of open-circuit voltage and the fill factor in CdTe nanocrystal solar
cells by using interface materials.
AB - Interface states influence the operation of nanocrystal (NC) solar cell carrier
transport, recombination and energetic mechanisms. In a typical CdTe NC solar
cell with a normal structure of a ITO/p-CdTe NCs/n-acceptor (or without)/Al
configuration, the contact between the ITO and CdTe is a non-ohm contact due to a
different work function (for an ITO, the value is ~4.7 eV, while for CdTe NCs,
the value is ~5.3 eV), which results in an energetic barrier at the ITO/CdTe
interface and decreases the performance of the NC solar cells. This work
investigates how interface materials (including Au, MoO(x) and C60) affect the
performance of NC solar cells. It is found that devices with interface materials
have shown higher V(oc) than those without interface materials. For the case in
which we used Au as an interface, we obtained a high open-circuit voltage of 0.65
V, coupled with a high fill factor (62%); this resulted in a higher energy
conversion efficiency (ECE) of 5.3%, which showed a 30% increase in the ECE
compared with those without the interlayer. The capacitance measurements indicate
that the increased V(oc) in the case in which Au was used as the interface is
likely due to good ohm contact between the Au's and the CdTe NCs' thin film,
which decreases the energetic barrier at the ITO/CdTe interface.
PMID- 25140735
TI - Multifunctional cyclotriphosphazene/hexagonal boron nitride hybrids and their
flame retarding bismaleimide resins with high thermal conductivity and thermal
stability.
AB - A novel hybridized multifunctional filler (CPBN), cyclotriphosphazene/hexagonal
boron nitride (hBN) hybrid, was synthesized by chemically coating hBN with
hexachlorocyclotriphosphazene and p-phenylenediamine, its structure was
systemically characterized. Besides, CPBN was used to develop new flame retarding
bismaleimide/o,o'-diallylbisphenol A (BD) resins with simultaneously high thermal
conductivity and thermal stability. The nature of CPBN has a strong influence on
the flame behavior of the composites. With the addition of only 5 wt % CPBN to BD
resin, the thermal conductivity increases 2 times; meanwhile the flame retardancy
of BD resin is remarkably increased, reflected by the increased limited oxygen
index, much longer time to ignition, significantly reduced heat release rate. The
thermogravimetric kinetics, structures of chars and pyrolysis gases, and cone
calorimeter tests were investigated to reveal the unique flame retarding
mechanism of CPBN/BD composites. CPBN provides multieffects on improving the
flame retardancy, especially in forming a protective char layer, which means a
more thermally stable and condensed barrier for heat and mass transfer, and thus
protecting the resin from further combustion.
PMID- 25140736
TI - Identification of genetic variants associated with alternative splicing using
sQTLseekeR.
AB - Identification of genetic variants affecting splicing in RNA sequencing
population studies is still in its infancy. Splicing phenotype is more complex
than gene expression and ought to be treated as a multivariate phenotype to be
recapitulated completely. Here we represent the splicing pattern of a gene as the
distribution of the relative abundances of a gene's alternative transcript
isoforms. We develop a statistical framework that uses a distance-based approach
to compute the variability of splicing ratios across observations, and a non
parametric analogue to multivariate analysis of variance. We implement this
approach in the R package sQTLseekeR and use it to analyze RNA-Seq data from the
Geuvadis project in 465 individuals. We identify hundreds of single nucleotide
polymorphisms (SNPs) as splicing QTLs (sQTLs), including some falling in genome
wide association study SNPs. By developing the appropriate metrics, we show that
sQTLseekeR compares favorably with existing methods that rely on univariate
approaches, predicting variants that behave as expected from mutations affecting
splicing.
PMID- 25140739
TI - Classical and non-classical redox reactions of Pd(II) complexes containing redox
active ligands.
AB - Reactivity studies of a Pd(II)-verdazyl complex reveal novel ligand-centred
reduction processes which trigger pseudo-reductive elimination at Pd. Reaction of
the complex with water induces a ligand-centred redox disproportionation. The
reduced verdazyl ligands can also be reversibly protonated.
PMID- 25140738
TI - Large sample area and size are needed for forest soil seed bank studies to ensure
low discrepancy with standing vegetation.
AB - A large number of small-sized samples invariably shows that woody species are
absent from forest soil seed banks, leading to a large discrepancy with the
seedling bank on the forest floor. We ask: 1) Does this conventional sampling
strategy limit the detection of seeds of woody species? 2) Are large sample areas
and sample sizes needed for higher recovery of seeds of woody species? We
collected 100 samples that were 10 cm (length) * 10 cm (width) * 10 cm (depth),
referred to as larger number of small-sized samples (LNSS) in a 1 ha forest plot,
and placed them to germinate in a greenhouse, and collected 30 samples that were
1 m * 1 m * 10 cm, referred to as small number of large-sized samples (SNLS) and
placed them (10 each) in a nearby secondary forest, shrub land and grass land.
Only 15.7% of woody plant species of the forest stand were detected by the 100
LNSS, contrasting with 22.9%, 37.3% and 20.5% woody plant species being detected
by SNLS in the secondary forest, shrub land and grassland, respectively. The
increased number of species vs. sampled areas confirmed power-law relationships
for forest stand, the LNSS and SNLS at all three recipient sites. Our results,
although based on one forest, indicate that conventional LNSS did not yield a
high percentage of detection for woody species, but SNLS strategy yielded a
higher percentage of detection for woody species in the seed bank if samples were
exposed to a better field germination environment. A 4 m2 minimum sample area
derived from power equations is larger than the sampled area in most studies in
the literature. Increased sample size also is needed to obtain an increased
sample area if the number of samples is to remain relatively low.
PMID- 25140737
TI - The cellular bromodomain protein Brd4 has multiple functions in E2-mediated
papillomavirus transcription activation.
AB - The cellular bromodomain protein Brd4 functions in multiple processes of the
papillomavirus life cycle, including viral replication, genome maintenance, and
gene transcription through its interaction with the viral protein, E2. However,
the mechanisms by which E2 and Brd4 activate viral transcription are still not
completely understood. In this study, we show that recruitment of positive
transcription elongation factor b (P-TEFb), a functional interaction partner of
Brd4 in transcription activation, is important for E2's transcription activation
activity. Furthermore, chromatin immunoprecipitation (ChIP) analyses demonstrate
that P-TEFb is recruited to the actual papillomavirus episomes. We also show that
E2's interaction with cellular chromatin through Brd4 correlates with its
papillomavirus transcription activation function since JQ1(+), a bromodomain
inhibitor that efficiently dissociates E2-Brd4 complexes from chromatin, potently
reduces papillomavirus transcription. Our study identifies a specific function of
Brd4 in papillomavirus gene transcription and highlights the potential use of
bromodomain inhibitors as a method to disrupt the human papillomavirus (HPV) life
cycle.
PMID- 25140740
TI - Hydrocarbons emitted by waggle-dancing honey bees increase forager recruitment by
stimulating dancing.
AB - Hydrocarbons emitted by waggle-dancing honey bees are known to reactivate
experienced foragers to visit known food sources. This study investigates whether
these hydrocarbons also increase waggle-dance recruitment by observing
recruitment and dancing behavior when the dance compounds are introduced into the
hive. If the hydrocarbons emitted by waggle-dancing bees affect the recruitment
of foragers to a food source, then the number of recruits arriving at a food
source should be greater after introduction of dance compounds versus a pure
solvent control. This prediction was supported by the results of experiments in
which recruits were captured at a feeder following introduction of dance
compounds into a hive. This study also tested two nonexclusive behavioral
mechanism(s) by which the compounds might stimulate recruitment; 1) increased
recruitment could occur by means of increasing the recruitment effectiveness of
each dance and/or 2) increased recruitment could occur by increasing the
intensity of waggle-dancing. These hypotheses were tested by examining video
records of the dancing and recruitment behavior of individually marked bees
following dance-compound introduction. Comparisons of numbers of dance followers
and numbers of recruits per dance and waggle run showed no significant
differences between dance-compound and solvent-control introduction, thus
providing no support for the first hypothesis. Comparison of the number of waggle
dance bouts and the number of waggle runs revealed significantly more dancing
during morning dance-compound introduction than morning solvent-control
introduction, supporting the second hypothesis. These results suggest that the
waggle-dance hydrocarbons play an important role in honey bee foraging
recruitment by stimulating foragers to perform waggle dances following periods of
inactivity.
PMID- 25140742
TI - Critical-care pain observation tool in critically ill patients.
PMID- 25140741
TI - A culture of respect: champions and models.
PMID- 25140743
TI - Move to improve: progressive mobility in the intensive care unit.
AB - Bed rest has detrimental consequences, and therefore in the ICU, progressive
early mobility should be the goal for every patient expected to survive. This
article examines the consequences of immobility, barriers experienced when
attempting to increase patients' mobility, and ways in which dedicated mobility
teams can overcome these barriers.
PMID- 25140744
TI - Where do you want to give report?
AB - Traditionally, nurses have met in a conference room to give each other end-of
shift report. Many hospitals are now moving to bedside report. Which does the
research support as best practice? What are the ethical and practical issues of
each? This article answers those questions.
PMID- 25140745
TI - Model for heart failure education.
AB - Heart failure (HF) is the heart's inability to meet the body's need for blood and
oxygen. According to the American Heart Association 2013 update, approximately
5.1 million people are diagnosed with HF in the United States in 2006. Heart
failure is the most common diagnosis for hospitalization. In the United States,
the HF direct and indirect costs are estimated to be US $39.2 billion in 2010. To
address this issue, nursing educators designed innovative teaching frameworks on
HF management both in academia and in clinical settings. The model was based on 2
resources: the American Association of Heart Failure Nurses (2012) national
nursing certification and the award-winning Pierce County Responsive Care
Coordination Program. The HF educational program is divided into 4 modules. The
initial modules offer foundational levels of Bloom's Taxonomy then progress to
incorporate higher-levels of learning when modules 3 and 4 are reached. The
applicability of the key components within each module allows formatting to
enhance learning in all areas of nursing, from the emergency department to
intensive care units to the medical-surgical step-down units. Also applicable
would be to provide specific aspects of the modules to nurses who care for HF
patients in skilled nursing facility, rehabilitation centers, and in the home
health care setting.
PMID- 25140746
TI - Cardiac comorbidities and sexual activity predict sexual self-perception and
adjustment.
AB - BACKGROUND: Changes in sexual satisfaction and sexual activity are often reported
by cardiac patients, although factors influencing sexual adjustment are not well
established. Knowledge of risk and protective factors can guide nurses in
addressing physical and psychological needs of patients. OBJECTIVES: We examined
predictors of sexual self-perception and adjustment in a cross section of cardiac
patients. METHODS: A nonexperimental, descriptive survey design was used to
examine overall sexual self-perception and adjustment, sexual anxiety, sexual
depression, sexual satisfaction, sexual self-efficacy, sexual activity, selected
demographic factors, and 20 cardiac and noncardiac comorbidities using a mailed
survey with a broad sampling of cardiac patients (n = 128). Data were analyzed
with descriptive statistics, t tests, and regression analysis. RESULTS: Fewer
cardiac conditions and being sexually active were significant predictors of
sexual self-perception and adjustment. Participants with hypertension reported
more sexual depression; those with myocardial infarction had higher scores for
both sexual anxiety and depression, and greater sexual anxiety occurred for those
with peripheral artery leg bypass. DISCUSSION: Positive sexual self-perception
and adjustment are linked to sexual activity and fewer cardiac problems. This
finding can be used to inform decisions about initiating sexual counseling.
PMID- 25140748
TI - Incivility among intensive care nurses: the effects of an educational
intervention.
AB - BACKGROUND: Incivility is a significant problem in nurse satisfaction and nurse
retention and can be detrimental to a patient's outcome; therefore, it would be
beneficial to educate nurses on ways to improve incivility in clinical practice.
OBJECTIVES: To determine if a nursing education program, utilizing case studies
and discussion of the nurses' experiences would increase awareness of incivility
and impact the number of perceived incidences by (1) assessing nurses' experience
of incivility along with discerning the perceived source of the incivility and
(2) educating the nurses, thus determining if the in-service education decreases
the incidence of incivility in the adult intensive care unit. METHODS: This is a
quantitative pilot study that utilized a 1-group preintervention and
postintervention test design. The intervention was a 60-minute educational
program. Twenty-one nurses completed the survey that assesses prevalence of
incivility by specific sources, such as nurses, physicians, supervisors, general
(other hospital employees), and patients before and after participation in the
education intervention. Descriptive statistics of the 5 dimensions of civility
and a total dimension score of civility were used. RESULTS: A total of 21 nurses
completed all parts of this study. The postintervention score had a higher mean
than the preintervention score in each of the dimensions. Higher scores indicate
incivility; thus, lower scores indicate civility. Therefore, more instances of
incivility were identified after intervention to increase awareness of
incivility. In addition, nurses perceived greater amounts of incivility from
patients and families, whereas the direct supervisor (team leaders) showed the
greatest amount of civility. A hierarchical regression revealed that race had the
largest negative impact, followed by nurses practicing for more than 5 years,
part-time status, and younger age, respectively. DISCUSSION: The outcomes in this
pilot study contradict much of the research on incivility in nursing, which
previously found that supervisors are more uncivil toward their staff nurses than
the rest of the staff. The results of the current study found that incivility
perceptions were higher in the postintervention survey; these findings suggest
that the education was effective, thus creating more awareness of incivility.
This could be a positive cultural turning point in nursing as it decreases
incivility, which in turn will help to decrease medical errors, attrition rates,
and the financial burden on hospitals.
PMID- 25140751
TI - Design, synthesis and biological characterization of thiazolidin-4-one
derivatives as promising inhibitors of Toxoplasma gondii.
AB - We designed and synthesized a large number of novel thiazolidin-4-one derivatives
for the evaluation of their anti-Toxoplasma gondii activity. This scaffold was
functionalized at the N1-hydrazine portion with aliphatic, cycloaliphatic and
(hetero)aromatic moieties. Then, a benzyl pendant was introduced at the lactamic
NH of the core nucleus to evaluate the influence of this chemical modification on
biological activity. The compounds were subjected to several in vitro assays to
assess their anti-parasitic efficacy, cytotoxicity on fibroblasts, inhibition of
tachyzoite invasion/attachment and replication after treatment. Results showed
that fourteen of these thiazole-based compounds compare favorably to control
compound trimethoprim in terms of parasite growth inhibition.
PMID- 25140752
TI - Discovery of Troger's base analogues as selective inhibitors against human breast
cancer cell line: design, synthesis and cytotoxic evaluation.
AB - A library of structurally diverse Troger's base analogues has been constructed
via unusual amination of methylene bridge employing Vilsmeier-Haack conditions as
well as by the incorporation of five and six membered heterocycles on the
aromatic core of Troger's base framework. The constructed structurally diverse
frameworks were evaluated for their cytotoxic activities against a panel of three
human cancer lines A549 (lung adenocarcinoma), MDAMB-231 (breast) and SK-N-SH
(neuroblastoma). From the activity profile obtained, a redesign of Troger's base
analogues led to the construction of more potent molecular entities. The study
led to development of a series of compounds with MDAMB-231 cell line specific
cytotoxicity. Of the 30 compounds synthesized and evaluated, 7 compounds were
found to possess cytotoxicity that is equivalent or better than standard drug
doxorubicin against MDAMB-231 cell line while only one compound was found to be
active against SK-N-SH cell line.
PMID- 25140753
TI - Hierarchical self-assembly of 'hard-soft' Janus particles into colloidal
molecules and larger supracolloidal structures.
AB - Here we report the self-assembly of 'hard-soft' micron-sized Janus particles into
clusters in aqueous media. The assembly process is induced by the desorption of a
polymeric stabiliser from the particles, that is polyvinylpyrrolidone (PVP). Upon
contact through collision and coalescence of the soft polymeric lobes, the newly
formed clusters adopt a minimized surface area to volume ratio, thereby forming
distinct microscopic supracolloidal analogues of simple molecular valance shell
electron pair repulsion (VSEPR) space-fill structures. To explain this behaviour,
the colloidal stability of our particle suspensions were studied with and without
an adsorbed steric surfactant. Simulations of expected cluster morphology,
compared with those from cryo-SEM analysis support the mechanism of assembly
driven by surface area minimization in the case of soft-soft interactions.
Altering the soft lobe size with respect to the hard lobe indicates a moderate
effect on number of primary particles per cluster. Additionally, higher order
structures of clusters containing a number of primary particles exceeding what is
possible for a 'solid' core cluster are observed. As such, we also investigated
the formation of suprastructures using a high number of 'hard-soft' Janus
particles and verified their effective Pickering stabilization of air bubbles.
PMID- 25140755
TI - Patient safety still lagging: advocates call for national patient safety
monitoring board.
PMID- 25140754
TI - The role of arginase and rho kinase in cardioprotection from remote ischemic
perconditioning in non-diabetic and diabetic rat in vivo.
AB - BACKGROUND: Pharmacological inhibition of arginase and remote ischemic
perconditioning (RIPerc) are known to protect the heart against
ischemia/reperfusion (IR) injury. PURPOSE: The objective of this study was to
investigate whether (1) peroxynitrite-mediated RhoA/Rho associated kinase (ROCK)
signaling pathway contributes to arginase upregulation following myocardial IR;
(2) the inhibition of this pathway is involved as a cardioprotective mechanism of
remote ischemic perconditioning and (3) the influence of diabetes on these
mechanisms. METHODS: Anesthetized rats were subjected to 30 min left coronary
artery ligation followed by 2 h reperfusion and included in two protocols. In
protocol 1 rats were randomized to 1) control IR, 2) RIPerc induced by bilateral
femoral artery occlusion for 15 min during myocardial ischemia, 3) RIPerc and
administration of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L
NMMA), 4) administration of the ROCK inhibitor hydroxyfasudil or 5) the
peroxynitrite decomposition catalyst FeTPPS. In protocol 2 non-diabetic and type
1 diabetic rats were randomosed to IR or RIPerc as described above. RESULTS:
Infarct size was significantly reduced in rats treated with FeTPPS,
hydroxyfasudil and RIPerc compared to controls (P<0.001). FeTPPS attenuated both
ROCK and arginase activity (P<0.001 vs. control). Similarly, RIPerc reduced
arginase and ROCK activity, peroxynitrite formation and enhanced phospho-eNOS
expression (P<0.05 vs. control). The cardioprotective effect of RIPerc was
abolished by L-NMMA. The protective effect of RIPerc and its associated changes
in arginase and ROCK activity were abolished in diabetes. CONCLUSION: Arginase is
activated by peroxynitrite/ROCK signaling cascade in myocardial IR. RIPerc
protects against IR injury via a mechanism involving inhibition of this pathway
and enhanced eNOS activation. The beneficial effect and associated molecular
changes of RIPerc is abolished in type 1 diabetes.
PMID- 25140756
TI - Near-infrared Raman spectroscopy for assessing biochemical changes of cervical
tissue associated with precarcinogenic transformation.
AB - Raman spectroscopy measures the inelastically scattered light from tissue that is
capable of identifying native tissue biochemical constituents and their changes
associated with disease transformation. This study aims to characterize the Raman
spectroscopic properties of cervical tissue associated with the multi-stage
progression of cervical precarcinogenic sequence. A rapid-acquisition fiber-optic
near-infrared (NIR) Raman diagnostic system was employed for tissue Raman
spectral measurements at 785 nm excitation. A total of 68 Raman spectra (23
benign, 29 low-grade squamous intraepithelial lesions (LSIL) and 16 high grade
squamous intraepithelial lesions (HSIL)) were measured from 25 cervical tissue
biopsy specimens, as confirmed by colposcopy-histopathology. The semi
quantitative biochemical modeling based on the major biochemicals (i.e., DNA,
proteins (histone, collagen), lipid (triolein) and carbohydrates (glycogen)) in
cervical tissue uncovers the stepwise accumulation of biomolecular changes
associated with progressive cervical precarcinogenesis. Multi-class partial least
squares-discriminant analysis (PLS-DA) together with leave-one tissue site-out,
cross-validation yielded the diagnostic sensitivities of 95.7%, 82.8% and 81.3%;
specificities of 100.0%, 92.3% and 88.5%,for discrimination among benign, LSIL
and HSIL cervical tissues, respectively. This work suggests that the Raman
spectral biomarkers have identified the potential to be used for monitoring the
multi-stage cervical precarcinogenesis, forming the foundation of applying NIR
Raman spectroscopy for the early diagnosis of cervical precancer in vivo at the
molecular level.
PMID- 25140757
TI - Endometriosis associated with relapsing ascites and pleural effusions.
PMID- 25140758
TI - Effect of Ganoderma applanatum mycelium extract on the inhibition of adipogenesis
in 3T3-L1 adipocytes.
AB - Ganoderma applanatum (GA) and related fungal species have been used for over 2000
years in China to prevent and treat various human diseases. However, there is no
critical research evaluating the functionality of GA grown using submerged
culture technology. This study aimed to evaluate the effects of submerged culture
GA mycelium (GAM) and its active components (protocatechualdehyde [PCA]) on
preadipocyte differentiation of 3T3-L1 cells. Mouse-derived preadipocyte 3T3-L1
cells were treated with differentiation inducers in the presence or absence of
GAM extracts. We determined triglyceride accumulations, glycerol-3-phosphate
dehydrogenase (GPDH) activities, and differentiation makers. PCA, the active
component of GAM extract, was also used to treat 3T3-L1 cells. The MTT assay
showed that the GAM extract (0.01-1 mg/mL) was not toxic to 3T3-L1 preadipocyte.
Treatment of cells with GAM extracts and its active components significantly
decreased the GPDH activity and lipid accumulation, a marker of adipogenesis, in
a dose-dependent manner. Western blot analysis results showed that the protein
expression levels of peroxisome proliferator-activated receptor gamma
(PPARgamma), CCAAT/enhancer-binding protein alpha (C/EBPalpha), and sterol
regulatory element-binding protein 1 (SREBP1) were inhibited by the GAM extract.
In addition, adipogenic-specific genes such as perilipin, fatty acid synthase
(FAS), fatty acid transport protein 1 (FATP1), and fatty acid-binding protein 4
(FABP4) decreased in a dose-dependent manner. Quantitative high-performance
liquid chromatography analysis showed that the GAM extract contained 1.14 mg/g
PCA. GAM extracts suppressed differentiation of 3T3-L1 preadipocytes, in part,
through altered regulation of PPARgamma, C/EBPalpha, and SREBP1. These results
suggest that GAM extracts and PCA may suppress adipogenesis by inhibiting
differentiation of preadipocytes.
PMID- 25140761
TI - Anti-inflammatory effects of ethanolic extract from Sargassum horneri (Turner) C.
Agardh on lipopolysaccharide-stimulated macrophage activation via NF-kappaB
pathway regulation.
AB - Inflammation is major symptom of the innate immune response by infection of
microbes. Macrophages, one of immune response related cells, play a role in
inflammatory response. Recent studies reported that various natural products can
regulate the activation of immune cells such as macrophage. Sargassum horneri
(Turner) C. Agardh is one of brown algae. Recently, various seaweeds including
brown algae have antioxidant and anti-inflammatory effects. However, anti
inflammatory effects of Sargassum horneri (Turner) C. Agardh are still unknown.
In this study, we investigated anti-inflammatory effects of ethanolic extract of
Sargassum horneri (Turner) C. Agardh (ESH) on RAW 264.7 murine macrophage cell
line. The ESH was extracted from dried Sargassum horneri (Turner) C. Agardh with
70% ethanol and then lyophilized at -40 degrees C. ESH was not cytotoxic to RAW
264.7, and nitric oxide (NO) production induced by LPS-stimulated macrophage
activation was significantly decreased by the addition of 200 MUg/mL of ESH.
Moreover, ESH treatment reduced mRNA level of cytokines, including IL-1beta, and
pro-inflammatory genes such as iNOS and COX-2 in LPS-stimulated macrophage
activation in a dose-dependent manner. ESH was found to elicit anti-inflammatory
effects by inhibiting ERK, p-p38 and NF-kappaB phosphorylation. In addition, ESH
inhibited the release of IL-1beta in LPS-stimulated macrophages. These results
suggest that ESH elicits anti-inflammatory effects on LPS-stimulated macrophage
activation via the inhibition of ERK, p-p38, NF-kappaB, and pro-inflammatory gene
expression.
PMID- 25140759
TI - Psychometric assessment of the craving to tan questionnaire.
AB - BACKGROUND: Researchers and clinicians suggest that excessive tanning may be a
behavioral addiction. Given the significance of craving in substance use, craving
may be a useful construct to assess in those who tan. OBJECTIVE: We designed this
study to assess the psychometric properties of an alcohol craving measure adapted
to measure past-week craving to tan. METHODS: Undergraduate students (n = 421)
who reported past-month tanning completed a battery of questionnaires that
assessed demographics, tanning-related characteristics, and psychopathology, in
addition to the Craving to Tan Questionnaire (CTQ). RESULTS: Analyses provided
support for a single factor CTQ with good internal consistency, construct
validity and convergent validity. CTQ scores were significantly higher among
problematic versus non-problematic and dependent versus non-dependent tanners.
CTQ scores were also associated with several tanning-related characteristics,
such money spent on tanning in a typical month, frequency of tanning, and
frequency of tanning-related problems. Additional analyses found that past-week
craving to tan was significantly associated with greater obsessive compulsive and
body dysmorphic symptoms. CONCLUSIONS: It may be useful in clinical settings to
identify those experiencing problems with tanning and in research to further
clarify the conceptualization of addiction-like tanning. However, the CTQ needs
further evaluation.
PMID- 25140762
TI - Impact of 5-h phase advance on sleep architecture and physical performance in
athletes.
AB - Travel across time zones causes jet lag and is accompanied by deleterious effects
on sleep and performance in athletes. These poor performances have been evaluated
in field studies but not in laboratory conditions. The purpose of this study was
to evaluate, in athletes, the impact of 5-h phase advance on the architecture of
sleep and physical performances (Wingate test). In a sleep laboratory, 16 male
athletes (age: 22.2 +/- 1.7 years, height: 178.3 +/- 5.6 cm, body mass: 73.6 +/-
7.9 kg) spent 1 night in baseline condition and 2 nights, 1 week apart, in phase
shift condition recorded by electroencephalography to calculate sleep
architecture variables. For these last 2 nights, the clock was advanced by 5 h.
Core body temperature rhythm was assessed continuously. The first night with
phase advance decreased total sleep time, sleep efficiency, sleep onset latency,
stage 2 of nonrapid eye movement (N2), and rapid eye movement (REM) sleep
compared with baseline condition, whereas the second night decreased N2 and
increased slow-wave sleep and REM, thus improving the quality of sleep. After
phase advance, mean power improved, which resulted in higher lactatemia.
Acrophase and bathyphase of temperature occurred earlier and amplitude decreased
in phase advance but the period was not modified. These results suggest that a
simulated phase shift contributed to the changes in sleep architecture, but did
not significantly impair physical performances in relation with early phase
adjustment of temperature to the new local time.
PMID- 25140764
TI - Structural insights of JAK2 inhibitors: pharmacophore modeling and ligand-based
3D-QSAR studies of pyrido-indole derivatives.
AB - In this study we have performed pharmacophore modeling and built a 3D QSAR model
for pyrido-indole derivatives as Janus Kinase 2 inhibitors. An efficient
pharmacophore has been identified from a data set of 51 molecules and the
identified pharmacophore hypothesis consisted of one hydrogen bond acceptor, two
hydrogen bond donors and three aromatic rings, i.e. ADDRRR. A powerful 3D-QSAR
model has also been constructed by employing Partial Least Square regression
analysis with a regression coefficient of 0.97 (R(2)) and Q(2) of 0.95, and
Pearson-R of 0.98.
PMID- 25140765
TI - A Noncausal Relation Between Casual Sex in Adolescence and Early Adult Depression
and Suicidal Ideation: A Longitudinal Discordant Twin Study.
AB - Research on relations between casual sex and mental health is inconclusive; while
some studies indicate casual sex may lead to more negative mental health (e.g.,
depression), other studies report no such relationship. Using a genetically
informed approach, this study examined whether earlier casual sex (i.e., ever
engaging in casual sex and number of casual sex partners) in adolescence has a
causal influence on later mental health in young adulthood (i.e., depressive
symptoms and suicidal ideation), as well as the reverse relationship (adolescent
negative mental health on young adult casual sex) by exploiting the quasi
experimental nature of discordant-twin models. Multilevel models that measured
within-twin and between-twin pair effects of adolescent casual sex were
estimated, using 714 twins (357 twin pairs) from the sibling subsample of the
National Longitudinal Study of Adolescent Health (Add Health). Results indicated
that there was no causal relationship between casual sex in adolescence and
higher levels of depressive symptoms or suicidal ideation in young adulthood, and
these effects did not differ by gender. There were also no causal relations
between adolescent depressive symptoms or suicidal ideation and casual sexual
experience in young adulthood. Implications for ways to increase scientific rigor
by using different methods (e.g., genetically informed analyses) are discussed.
PMID- 25140763
TI - Influence of HMB supplementation and resistance training on cytokine responses to
resistance exercise.
AB - PURPOSE: The purpose of this study was to determine the effects of a
multinutritional supplement including amino acids, beta-hydroxy-beta
methylbutyrate (HMB), and carbohydrates on cytokine responses to resistance
exercise and training. METHODS: Seventeen healthy, college-aged men were randomly
assigned to a Muscle ArmorTM (MA; Abbott Nutrition, Columbus, OH) or placebo
supplement group and 12 weeks of resistance training. An acute resistance
exercise protocol was administered at 0, 6, and 12 weeks of training. Venous
blood samples at pre-, immediately post-, and 30-minutes postexercise were
analyzed via bead multiplex immunoassay for 17 cytokines. RESULTS: After 12 weeks
of training, the MA group exhibited decreased interferon-gamma (IFN-gamma) and
interleukin (IL)-10. IL-1beta differed by group at various times. Granulocyte
colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating
factor (GM-CSF), IL-6, IL-7, IL-8, IL-12p70, IL-13, IL-17, monocyte
chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1 beta
(MIP-1beta) changed over the 12-week training period but did not differ by group.
CONCLUSIONS: Twelve weeks of resistance training alters the cytokine response to
acute resistance exercise, and supplementation with HMB and amino acids appears
to further augment this result.
PMID- 25140766
TI - [Risk factors for invasive pulmonary fungal infection in children].
AB - OBJECTIVE: To analyze the risk factors for invasive pulmonary fungal infection
(IPFI) and to provide a theoretical basis for the early prevention and treatment
of IPFI. METHODS: A retrospective case-control study was conducted on the
clinical data of children hospitalized in the pediatric intensive care unit
between January 2012 and March 2013. These children consisted of 48 patients with
a clinical diagnosis of IPFI (IPFI group) and 106 pneumonia patients without a
clinical diagnosis of IPFI (non-IPFI group). The clinical date of the two groups
were compared and analyzed. The main risk factors for the development of IPIF
were identified by unconditional multivariate logistic regression analysis.
RESULTS: Compared with the non-IPIF group, the IPIF group had significantly lower
mean age and serum albumin level (P<0.01), significantly longer mean length of
hospital stay, duration of antibiotic use, and duration of corticosteroid use
(P<0.01), and significantly higher rates of malnutrition, invasive mechanical
ventilation, indwelling catheter use, oropharyngeal fungal infection, and
diarrhea (P<0.05). Multivariate logistic regression analysis showed that invasive
mechanical ventilation, diarrhea, long duration of corticosteroid use, long
duration of antibiotic use, young age, and low serum albumin level were
independent risk factors for the development of IPFI. CONCLUSIONS: For the
infants with suspected IPFI for whom pathogenic examination is difficult to
perform, IPFI should be considered in cases of invasive mechanical ventilation,
diarrhea, long-time uses of broad-spectrum antibiotics and corticosteroids and
hypoalbuminemia, and empirical antifungal therapy should be performed as soon as
possible.
PMID- 25140767
TI - [Risk factors for pleural lung disease in children with juvenile idiopathic
arthritis].
AB - OBJECTIVE: To investigate the risk factors for pleural lung disease (PLD) in
children with juvenile idiopathic arthritis (JIA) and to provide a basis for the
early diagnosis and timely treatment of this disease. METHODS: A total of 360
children with a confirmed diagnosis of JIA were enrolled, and their clinical data
were retrospectively analyzed. All patients underwent a chest X-ray. The patients
with PLD were assigned to PLD group, while those without PLD were assigned to non
PLD group. The clinical, imaging, and laboratory results of JIA patients with PLD
were analyzed. RESULTS: Among the 360 JIA patients, 43 (11.9%) had PLD, and 9
(21%) of them had respiratory symptoms. Chest X-ray findings mainly included
interstitial pneumonitis (53.5%) and pleurisy and/or pleural effusion (38.1%). In
the 43 cases of JIA-PLD, 4 (9.3%) had normal chest X-ray findings but abnormal
chest CT findings. The incidence of PLD was relatively high in patients aged
under 3 years and those aged 12 years or above. Children with systemic JIA had a
relatively high incidence of PLD. Compared with the non-PLD group, the PLD group
had a significantly higher incidence of anemia, elevated white blood cell (WBC)
count and IgG levels in peripheral blood, and positive rheumatoid factors or
antinuclear antibodies (P<0.05). CONCLUSIONS: Among children with JIA, PLD is
mostly seen in patients with systemic JIA or aged <3 years or >= 12 years,
especially those with anemia, elevated WBC count and IgG levels, and positive
rheumatoid factors or antinuclear antibodies. For JIA patients with PLD,
interstitial pneumonitis is usually seen on chest X-ray or CT, but respiratory
symptoms are rarely observed. Routine use of high-resolution chest CT is
recommended for early diagnosis and timely treatment of PLD in children with JIA.
PMID- 25140768
TI - [Pathogenic analysis of ventilator-associated pneumonia in the pediatric
intensive care unit in high-altitude areas].
AB - OBJECTIVE: To investigate the pathogens of ventilator-associated pneumonia (VAP)
and their drug resistance in the pediatric intensive care unit (PICU) in high
altitude areas and to provide a clinical basis for the prevention and treatment
of VAP. METHODS: A total of 94 children with VAP hospitalized in the PICU in high
altitude areas between June 2011 and June 2013 were recruited. Their lower
respiratory tract secretions were collected for bacterial culture and drug
sensitivity test. RESULTS: Of the 94 children with VAP, 22 (23%) had a single
bacterial infection, and 72 (77%) had mixed infections, mostly with Klebsiella
pneumoniae and Acinetobacter baumannii (17 cases, 27%). Of the 178 isolated
strains of pathogens, 139 (78%) were Gram-negative bacteria (G- bacteria), mainly
including Klebsiella pneumoniae, Stenotrophomonas maltophilia, Acinetobacter
baumannii, and Pseudomonas aeruginosa, 26 (15%) were Gram-positive bacteria (G+
bacteria), mainly including Staphylococcus aureus, and 13 (7%) were fungi, mainly
including Candida albicans. Most G- bacteria had a high drug resistance.
Pseudomonas aeruginosa was extensively drug-resistant. Acinetobacter baumannii
was only highly sensitive to cefoperazone/sulbactam and imipenem. Multidrug
resistance (methicillin resistance) was found in G+ bacteria, for which
vancomycin was effective. CONCLUSIONS: The pathogens of VAP in high-altitude
areas are mostly G- bacteria, which may cause mixed infections and develop drug
resistance. This provides guidance for the rational use of antimicrobial drugs
and the development of key prevention and control measures for VAP.
PMID- 25140769
TI - [Values of a combination of multiple less invasive or non-invasive examinations
in the diagnosis of pediatric sputum-negative pulmonary tuberculosis].
AB - OBJECTIVE: To study the values of a combination of multiple less invasive or non
invasive examinations including chest computed tomography (CT) scan, purified
protein derivative (PPD) test, erythrocyte sedimentation rate (ESR) test, and C
reactive protein (CRP) test in the diagnosis of pediatric sputum-negative
pulmonary tuberculosis (TB). METHODS: A retrospective analysis was performed on
the clinical data of 269 children with confirmed pulmonary TB. Clinical symptoms
and test results were analyzed and compared between the sputum-negative group
(161 patients) and the sputum-positive group (108 patients). RESULTS: The sputum
negative group had atypical clinical symptoms, with fewer typical or relatively
specific imaging features compared with the sputum-positive group. The positive
rates of PPD, ESR, and CRP tests for the sputum-negative group were 39.1%, 44.1%,
and 56.5%, respectively, versus 55.6%, 79.6%, and 59.3% for the sputum-positive
group. There were significant differences in the positive rates of PPD and ESR
tests between the two groups (P<0.05). More than 80% of the patients in each
group were diagnosed with pulmonary TB according to three or four less invasive
or non-invasive tests, without significant difference in the positive rate
between the two groups (P>0.05). Forty-six patients in the sputum-negative group
underwent bronchoscopy, and morphological changes with a diagnostic value and/or
etiological and pathological evidence were observed in 40 (87.0%) of them.
CONCLUSIONS: The diagnosis rate of pediatric sputum-negative pulmonary TB can be
increased by combining tests including chest CT scan, PPD test, ESR test, and CRP
test. Bronchoscopy is a reliable method for the auxiliary diagnosis of pediatric
sputum-negative pulmonary TB if the combining tests cannot provide compelling
evidence.
PMID- 25140770
TI - [Application of asthma predictive index-based group therapy in wheezing children
under 5 years of age].
AB - OBJECTIVE: To study the application value of asthma predictive index (API)-based
group therapy in wheezing children under 5 years of age. METHODS: A total of 239
wheezing children under 5 years of age were divided into API-positive (n=126) and
API-negative groups (n=113). Each group was randomly assigned to inhaled
corticosteroids (ICS) subgroup and montelukast sodium (leukotriene receptor
antagonist, LTRA) subgroup. The ICS and LTRA subgroups received the same drug
therapy at the same dosage within the first four weeks of treatment. In the
stable period of disease, the ICS subgroup only received aerosol inhalation of
budesonide suspension, while the LTRA group was orally given montelukast sodium
only. Asthma symptom scores were assessed and recorded at different time points.
RESULTS: In the first four weeks of treatment, ICS and LTRA were effective both
in the API-positive and API-negative groups; the two groups showed significant
improvements in asthma symptom scores, and the asthma symptom score showed no
significant difference between the ICS and LTRA subgroups of each group. After 24
weeks of treatment, the two therapies were still effective; in the API-positive
group, the LTRA subgroup had a better treatment outcome than the ICS subgroup,
but there was no significant difference in treatment outcome between the LTRA and
ICS subgroups of the API-negative group. CONCLUSIONS: For wheezing children under
5 years of age, therapeutic strategies can be chosen based on API in the stable
period of disease, so as to better control wheezing.
PMID- 25140771
TI - [Clinical application of tidal breathing lung function test in 1-4 years old
children with wheezing diseases].
AB - OBJECTIVE: To study the clinical significance of tidal breathing lung function
test in 1-4 years old children with wheezing diseases. METHODS: A total of 141 1
4 years old children with wheezing diseases were enrolled as the observed groups
(41 cases of asthma, 54 cases of asthmatic bronchitis, and 46 cases of
bronchopneumonia). Thirty children without respiratory diseases were enrolled as
the control group. All the recruits underwent tidal breathing lung function test.
The observed groups underwent bronchial dilation test, and tidal breathing flow
volume (TBFV) parameters were evaluated before and after bronchial dilation test.
RESULTS: The observed groups showed obstructive ventilatory disorder (65%)
according to the TBFV loop, and their ratio of time to peak tidal expiratory flow
(TPTEF) to total expiratory time (TE) and ratio of volume to peak expiratory flow
(VPEF) to total expiratory volume (VE) were significantly lower than in the
control group (P<0.05). The asthma subgroup had significantly improved TPTEF/TE
and VPEF/VE after bronchial dilation test (P<0.05). Taking an improvement rate of
>= 15% either for TPTEF/TE or for VPEF/VE as an indicator of positive bronchial
dilation test, the bronchial dilation test had a sensitivity of 47% and a
specificity of 84% in diagnosing asthma in 1-4 years old children. The positive
rate was 28% among the children in the asthma subgroup with an TPTEF/TE ratio of
>= 23% before bronchial dilation test, versus 65% in those with an TPTEF/TE ratio
of <23%. CONCLUSIONS: Obstructive ventilatory disorder is the main impairment of
tidal breathing lung function in 1-4 years old children with wheezing diseases.
Tidal breathing bronchial dilation test can reflect a reversal of airway
obstruction to a certain extent. The sensitivity of bronchial dilation test for
the diagnosis of asthma is not satisfactory in 1-4 years old children with
wheezing diseases, but this test has a relatively high diagnostic value in
children with severe airway obstruction.
PMID- 25140773
TI - [Expression of TGF-beta1 and PAI-1 in premature infants with bronchopulmonary
dysplasia].
AB - OBJECTIVE: To study the expression of transforming growth factor-beta1 (TGF
beta1) and plasminogen activator inhibitor-1 (PAI-1) and its significance in
premature infants with bronchopulmonary dysplasia (BPD). METHODS: A retrospective
analysis was performed on the clinical data of 96 very low birth weight infants
(gestational age of <= 32 weeks) who survived for more than 28 days and were
admitted to the Neonatal Intensive Care Unit between January 2010 and December
2012. These subjects were divided into BPD group (n=21) and non-BPD group (n=75).
The expression of TGF-beta1 and PAI-1 in blood was measured by ELISA. RESULTS:
The levels of TGF-beta1 and PAI-1 in the BPD group increased gradually from the
7th day to the 14th day and then to the 21st day after birth, and were
significantly higher than in the non-BPD group at all time points (P<0.01). The
TGF-beta1 and PAI-1 levels in the non-BPD group on the 7th, 14th, and 21st days
after birth were not significantly different from each other (P>0.05).
CONCLUSIONS: The expression of TGF-beta1 and PAI-1 in blood is elevated in
premature infants with BPD, which may be associated with the development of BPD.
PMID- 25140772
TI - [Efficacy of inhaled nitric oxide in premature infants with hypoxic respiratory
failure].
AB - OBJECTIVE: To investigate the safety and efficacy of low-concentration inhaled
nitric oxide (NO) in the treatment of hypoxic respiratory failure (HRF) among
premature infants. METHODS: Sixty premature infants (gestational age <= 34 weeks)
with HRF were randomized into NO and control groups between 2012 and 2013, with
30 cases in each group. Both groups received nasal continuous positive airway
pressure (nCPAP) or mechanical ventilation. NO inhalation was continued for at
least 7 days or until weaning in the NO group. The general conditions, blood gas
results, complications, and clinical outcomes of the two groups were analyzed.
RESULTS: The NO group showed significantly more improvement in blood gas results
than the control group after 12 hours of treatment (P<0.05). After that, the
change in oxygenation status over time showed no significant difference between
the two groups (P>0.05). There were no significant differences in total time of
assisted ventilation and duration of oxygen therapy between the two groups
(P>0.05). The incidence of bronchopulmonary dysplasia (BPD), patent ductus
arteriosus, necrotizing enterocolitis, retinopathy of prematurity, and
pneumothorax in infants showed no significant differences between the NO and
control groups (P>0.05), but the incidence of IVH and mortality were
significantly lower in the NO group than in the control group (7% vs 17%, P<0.05;
3% vs 13%, P<0.05). CONCLUSIONS: NO inhalation may improve oxygenation status and
reduce the mortality in premature infants with HRF, but it cannot reduce the
incidence of BPD and the total time of mechanical ventilation or nCPAP and
duration of oxygen therapy. NO therapy may have a brain-protective effect for
premature infants with HRF and does not increase clinical complications.
PMID- 25140774
TI - [Effects of enteral nutrition starting time on digestive function and growth rate
in very low birth weight infants].
AB - OBJECTIVE: To study the appropriate time of starting enteral nutrition and
observe the effects of different enteral nutrition starting times on the
digestive function, growth rate, and nosocomial infection rate in very low birth
weight infants (VLBWI). METHODS: All the VLBWI admitted to the neonatal intensive
care unit between February and December, 2012 were selected. Depending on
different times of starting enteral nutrition, these infants were divided into
three groups: <= 3 days (n=116), 4-6 days (n=36), and >= 7 days (n=26). The
effects of different enteral nutrition starting times on digestive function,
growth rate and nosocomial infection rate were analyzed. RESULTS: The <= 3 days
group had significantly higher milk intake than the other two groups at one week
after birth; the <= 3 days and 4-6 days group had significantly higher milk
intake than the >= 7 days group at two and three weeks after birth. The growth
rate showed no significant differences between the three groups. The <= 3 days
group had a significantly shorter time of central venous catheterization than the
other two groups, and the >= 7 days group had a significantly longer time to full
enteral feeding than the other two groups. The nosocomial infection rate of the
<= 3 days group (13.8%) was significantly lower than that of the >= 7 days group
(46.2%). CONCLUSIONS: For VLBWI, the time of starting enteral nutrition has no
impact on growth rate, but starting enteral nutrition early can promote the
development of gastrointestinal function, increase milk intake, shorten the time
to full enteral feeding, reduce the time of central venous catheterization, and
significantly reduce nosocomial infection rate.
PMID- 25140775
TI - [A co-word analysis of current research on neonatal jaundice].
AB - OBJECTIVE: To investigate the research on neonatal jaundice in recent years by co
word analysis and to summarize the hot spots and trend of research in this field
in China. METHODS: The CNKI was searched with "neonate" and "jaundice" as the key
words to identify the papers published from January 2009 to July 2013 that were
in accordance with strict inclusion and exclusion criteria. To reveal the
relationship between different high-frequency key words, Microsoft Office Excel
2013 was used for statistical analysis of key words, and Ucinet 6.0 and Netdraw
were used for co-occurrence analysis. RESULTS: A total of 2 054 papers were
included, and 44 high-frequency key words were extracted. The current hotspots of
research on neonatal jaundice in China were displayed, and the relationship
between different high-frequency key words was presented. CONCLUSIONS: There has
been in-depth research on clinical manifestations and diagnosis of neonatal
jaundice in China, but further research is needed to investigate the etiology,
mechanism, and treatment of neonatal jaundice.
PMID- 25140777
TI - [Efficacy of levetiracetam combined with short-term clonazepam in treatment of
electrical status epilepticus during sleep in children with benign childhood
epilepsy with centrotemporal spikes].
AB - OBJECTIVE: To study the efficacy of levetiracetam (LEV) combined with short-term
clonazepam (CZP) in the treatment of electrical status epilepticus during sleep
(ESES) in children with benign childhood epilepsy with centrotemporal spikes
(BECCT). METHODS: Fifteen children (9 boys and 6 girls) diagnosed with BECCT with
ESES, who had continuous spike-and-wave accounting for over 85% of the non-rapid
eye movement sleep as monitored by 24-hours ambulatory EEG or 3-hours video EEG,
were enrolled. The clinical manifestations and EEG characteristics of patients
were retrospectively analyzed. These children received two months of CZP
treatment in addition to oral LEV [20-40 mg/(kg.d)]. All patients were followed
up for 6-18 months. RESULTS: The 15 children were orally given LEV in the early
stage, but showed no improvement when reexamined by EEG or had seizures during
treatment. Then, they received LEV in combination with short-term CZP. Re
examinations at 1 and 6 months after treatment showed that 14 cases had
significantly reduced discharge (only little discharge in the Rolandic area) or
no discharge, as well as completely controlled seizure; one case had recurrent
ESES and two epileptic seizures during follow-up. The recurrent case received the
combination therapy again, and re-examinations 1 and 6 months later revealed
normal EEG; no seizure occurred in the 8 months of follow-up. CONCLUSIONS: LEV
combined with short-term CZP is effective and has few side effects in treating
ESES syndrome among children with BECCT.
PMID- 25140776
TI - [Clinical analysis of 10 cases of pediatric Crohn's disease].
AB - OBJECTIVE: To study the clinical features and treatment of pediatric Crohn's
disease (CD). METHODS: Clinical data of 10 children with active CD diagnosed
between 2005 and 2013 were retrospectively reviewed. RESULTS: Abdominal pain,
diarrhea, and bloody stools were the most common symptoms in these patients,
usually accompanied by different degrees of growth retardation and nutritional
disorders. Fever was the main extraintestinal manifestation. Enteroscopy showed
discontinuous and segmental mucosal hyperaemia and erosion, cobblestone
appearance and mucosal ulceration. Abdominal ultrasound revealed uneven and
segmental thickening of the intestinal wall. The pathological esamination showed
many lymphocytes, eosinophils and plasma cells infiltrating into the lamina
propria and partial atrophy of mucosal gland. C-reactive protein (CRP) level was
significantly lower in the remission stage than in the acute stage and the
recurrence stage (P<0.05). The erythrocyte sedimentation rate (ESR) was
significantly lower in the remission stage than in the recurrence stage (P<0.05).
Among mild cases identified by the pediatric Crohn's disease activity index
(PCDAI) in the early stage of disease, the induced remission rate and maintained
remission rate were 100% and 67%, respectively, with oral 5-aminosalicylic acid
(5-ASA) and adrenocortical hormone. Among moderate and severe cases identified by
the PCDAI, the partial remission rate was 100% with 5-ASA and adrenocortical
hormone, but the maintained remission rate was not so good and the recurrence
rate of disease was high. CONCLUSIONS: Pediatric CD has no specific clinical
manifestations and laboratory test results. ESR and CRP can be used as the
markers for evaluating the disease progression. 5-ASA has certain efficacy in
inducing and maintaining remission of pediatric CD. There is a certain
correlation between treatment outcome and the PCDAI score in the early stage of
disease.
PMID- 25140778
TI - [Clinical value of cranial MRI in the diagnosis and treatment of central nervous
system candidiasis].
AB - OBJECTIVE: To study the clinical value of cranial magnetic resonance imaging
(MRI) in the diagnosis and treatment of central nervous system candidiasis
(CNSC), which has no specific clinical manifestations and has no rapid and
specific diagnostic tools. METHODS: A retrospective analysis was performed on the
clinical data of 10 children who were diagnosed with CNSC in Beijing Children's
Hospital Affiliated to Capital Medical University between 2009 and 2013. RESULTS:
Nine of the 10 children underwent cranial MRI within 8 days after admission, and
5 of the 9 children underwent contrast-enhanced MRI at the same time. Eight of
the 9 children showed the features of meningoencephalitis, and 6 cases were
accompanied by varying degrees of brain atrophy; one case showed hydrocephalus
and cerebral abscess, and another case showed leukoencephalopathy. Six cases were
found to have the features of cerebral vasculitis after infection in the first
MRI after admission, including cerebral infarction (2 cases), venous sinus
thrombosis (3 cases), and Moyamoya disease (1 case). Infectious granulomatous
lesions were confirmed by contrast-enhanced MRI in 3 cases. Given the clinical
manifestations, 8 of the 9 cases were diagnosed as suspected CNSC after MRI, and
7 of these cases received antifungal therapy before the pathogen test results
were returned. The lesions on MRI were improved in 6 cases after 3-4 weeks of
antifungal treatment. All the 10 children were diagnosed with CNSC by positive
cerebrospinal fluid culture results. CONCLUSIONS: Cranial MRI, especially
contrast-enhanced MRI, is of great significance for the diagnosis and treatment
of CNSC. To confirm the guidance of MRI in the diagnosis and treatment of CNSC,
further case-control studies are needed.
PMID- 25140779
TI - [Association of folate metabolism genes MTRR and MTHFR with complex congenital
abnormalities among Chinese population in Shanxi Province, China].
AB - OBJECTIVE: To explore the association of polymorphisms in folate metabolism
genes, methionine synthase reductase (MTRR) gene and 5,10
methylenetetrahydrofolate reductase (MTHFR) gene, with complex congenital
abnormalities and to further investigate its association with complex congenital
abnormalities derived from three germ layers. METHODS: A total of 250 cases of
birth defects (with complex congenital abnormalities including congenital heart
disease, neural tube defects, and craniofacial anomalies) in Shanxi Province,
China were included in the study. MTRR single nucleotide polymorphism (SNP)
(rs1801394) and MTHFR SNP (rs1801133) were genotyped by the SNaPshot method, and
the genotyping results were compared with those of controls (n=420). RESULTS:
SNPs rs1801394 and rs1801133 were associated with multiple birth defects. For the
recessive model, individuals with GG genotype at rs1801394 and CC genotype at
rs1801133 had a relatively low risk of developing birth defects, so the two
genotypes were protective factors against birth defects. The homozygous recessive
genotype at rs1801133, which served as a protective factor, was associated with
ectoderm- or endoderm-derived complex congenital abnormalities, while the
homozygous recessive genotype at rs1801394, which served as a protective factor,
was associated with ectoderm-, mesoderm- or endoderm-derived complex congenital
abnormalities. CONCLUSIONS: Among the Chinese population in Shanxi Province, the
SNPs in folate metabolism genes (MTRR and MTHFR) are associated with complex
congenital abnormalities and related to ectoderm, mesoderm or endoderm
development.
PMID- 25140780
TI - [Analysis of single nucleotide polymorphisms at IL-6-174 and TNF-beta NcoI in
Chinese Han children in Guangzhou, China].
AB - OBJECTIVE: To investigate the single nucleotide polymorphisms (SNPs) at
interleukin 6 (IL-6)-174 and TNF-beta NcoI in Chinese Han children in Guangzhou,
China and to provide basic information for study on the association between IL-6
174 and TNF-beta NcoI polymorphisms and systemic inflammatory response syndrome
(SIRS). METHODS: Allele-specific polymerase chain reaction and polymerase chain
reaction-restriction fragment length polymorphism were used to determine the SNPs
at IL-6-174 and TNF-beta NcoI in 481 children selected from the Han population in
Guangzhou in 2012. Genotype analysis and comparison with other populations were
made with reference to relevant literature. RESULTS: Chinese Han children in
Guangzhou had only GG genotype at IL-6-174, and the SNP at this locus was rare or
not seen in the Han population in Guangzhou. At TNF-beta NcoI, the frequencies of
TNF-beta 1*1, TNF-beta 1*2, and TNF-beta 2*2 genotypes were 24.7%, 49.7%, and
25.6%, respectively. The sample distribution was in accordance with Hardy
Weinberg equilibrium. The TNF-beta 1 allele frequency was significantly higher in
Guangzhou Han population than in European and American white population (P<0.05).
CONCLUSIONS: TNF-beta NcoI SNP is prevalent in the Han population in Guangzhou,
and the distribution of alleles is significantly different from that in the white
population. The sample from an Hardy-Weinberg equilibrium population can be
further used for study on the association between TNF-beta NcoI SNP and SIRS in
Chinese Han children in Guangzhou. IL-6-174 SNP is rare or not seen in the Han
population in Guangzhou, so SNP at this locus cannot be selected for disease
association analysis.
PMID- 25140782
TI - [Clinical analysis of pediatric infectious atelectasis].
PMID- 25140781
TI - [Effect of UCP2-siRNA on inflammatory response of cardiomyocytes induced by
septic serum].
AB - OBJECTIVE: To study the effect of uncoupling protein 2 (UCP2)-siRNA on the
inflammatory response of rat cardiomyocytes (H9C2) induced by septic serum and to
investigate the possible role of UCP2 in the development of septic
cardiomyopathy. METHODS: Serum samples were separately collected from normal rats
and septic rats. Cultured rat cardiac cells (H9C2) were randomly divided into
blank control, normal serum, 10% septic serum, UCP2-siRNA+10% septic serum and
negative siRNA+10% septic serum groups. Stimulation with 10% septic serum was
performed for 12 hours in relevant groups. The mRNA expression of tumor necrosis
factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) was measured by RT
PCR. The expression of phosphorylated p38 mitogen-activated protein kinase (p-p38
MAPK) and nuclear factor-kappa B (NF-kappaB) was measured by Western blot.
RESULTS: The expression levels of p-p38 and NF-kappaB in the UCP2-siRNA+10%
septic serum group were significantly higher than in the 10% septic serum group
(P<0.05). The UCP2-siRNA+10% septic serum group had a significantly higher TNF
alpha mRNA expression than the 10% septic serum group (P<0.01), but IL-1beta mRNA
expression showed no significant difference between the two groups. CONCLUSIONS:
UCP2 plays a regulatory role in the activation of p38 MAPK and NF-kappaB and the
expression of downstream inflammatory mediators in H9C2 cells stimulated with
septic serum.
PMID- 25140783
TI - [Effectiveness of external propranolol gel for treatment of superficial infantile
hemangioma].
PMID- 25140784
TI - [A case report of Phelan-McDermid syndrome].
PMID- 25140785
TI - [Corpus callosum damage detected by MRI in a boy with herpes simplex
encephalitis].
PMID- 25140786
TI - [Cutaneous myiasis in a young child].
PMID- 25140787
TI - [MonoMAC syndrome].
AB - MonoMAC syndrome is a newly discovered immune deficiency syndrome caused by GATA
2 mutation, which is an autosomal dominant genetic disease. MonoMAC syndrome has
typical immune cell abnormalities, with severe infection and is prone to develop
into a hematological disease. Therapeutics for this disease mainly relies on
symptomatic treatment and hematopoietic stem cell transplantation. In this paper,
the research advances in clinical manifestations, laboratory tests, pathogenesis,
diagnosis and treatment of MonoMAC syndrome are reviewed.
PMID- 25140788
TI - Removal of the iodinated X-ray contrast medium diatrizoate by anaerobic
transformation.
AB - The iodinated X-ray contrast medium diatrizoate is known to be very persistent in
current wastewater treatment as well as in environmental compartments. In this
study, the potential of anaerobic processes in soils, sediments, and during
wastewater treatment to remove and transform diatrizoate was investigated. In
anaerobic batch experiments with soil and sediment seven biologically formed
transformation products (TPs) as well as the corresponding transformation pathway
were identified. The TPs resulted from successive deiodinations and
deacetylations. The final TP 3,5-diaminobenzoic acid (DABA) was stable under
anaerobic conditions. However, DABA was further transformed under air atmosphere,
indicating the potential for the mineralization of diatrizoate by combining
anaerobic and aerobic conditions. With the development of a methodology using
complementary liquid chromatography-electrospray ionization-tandem mass
spectrometry and liquid chromatography-inductively coupled plasma-mass
spectrometry techniques, all identified TPs were quantified and the mass balance
could be closed without having authentic standards for four of the TPs available.
The detection and quantification of diatrizoate TPs in groundwater, in technical
wetlands with anaerobic zones, and in a pilot wastewater treatment plant
established for anaerobic treatment highlights the transferability and up-scaling
of the results attained by laboratory experiments to environmental conditions.
PMID- 25140789
TI - Attitudes to aging in midlife are related to health conditions and mood.
AB - BACKGROUND: Health is an important aspect of individuals' lives as they age. The
aim of this study was to examine the relationship of sociodemographic factors,
diagnosed chronic health conditions, and current depression with attitudes to
aging in midlife. METHODS: A cross-sectional baseline analysis was conducted on
the first 300 participants from the Canterbury Health, Ageing and Life Course
study in New Zealand, a stratified randomized community longitudinal study of
adults recruited between 49 and 51 years. Attitudes were measured using the
Attitudes to Aging Questionnaire (AAQ) and analyzed with a range of prevalent
diagnosed chronic conditions, current depression, and sociodemographic variables.
RESULTS: Individuals perceived their physical aging more negatively after a
diagnosis of hypertension, arthritis or asthma. Diagnosed lifetime depression and
anxiety, and current depression, showed strong relationships with attitudes to
aging across domains. After controlling for sociodemographic factors and current
depression, individuals with diagnosed hypertension, arthritis, asthma, lifetime
depression or anxiety continued to report significantly more negative attitudes
to aging. Current depression showed the strongest associations with attitudes to
aging and mediated relationships of health on attitudes to aging. CONCLUSIONS:
Physical and mental health are related to attitudes to aging. Most chronic
conditions examined are significantly associated with attitudes toward aging in
the physical change domain. Diagnosed lifetime depression and anxiety, and
current depression, are negatively related across attitudinal domains.
Individuals can feel positive about aging while experiencing poorer health, but
this is more difficult in the presence of low mood.
PMID- 25140791
TI - Fungal siderophore metabolism with a focus on Aspergillus fumigatus.
AB - Siderophores are chelators synthesized by microbes to sequester iron. This
article summarizes the knowledge on the fungal siderophore metabolism with a
focus on Aspergillus fumigatus. In recent years, A. fumigatus became a role model
for fungal biosynthesis, uptake and degradation of siderophores as well as
regulation of siderophore-mediated iron handling and the elucidation of
siderophore functions. Siderophore functions comprise uptake, intracellular
transport and storage of iron. This proved to be crucial not only for adaptation
to iron starvation conditions but also for germination, asexual and sexual
propagation, antioxidative defense, mutual interaction, microbial competition as
well as virulence in plant and animal hosts. Recent studies also indicate the
high potential of siderophores and its biosynthetic pathway to improve diagnosis
and therapy of fungal infections.
PMID- 25140792
TI - Are pharmaceuticals with evolutionary conserved molecular drug targets more
potent to cause toxic effects in non-target organisms?
AB - The ubiquitous use of pharmaceuticals has resulted in a continuous discharge into
wastewater and pharmaceuticals and their metabolites are found in the
environment. Due to their design towards specific drug targets, pharmaceuticals
may be therapeutically active already at low environmental concentrations.
Several human drug targets are evolutionary conserved in aquatic organisms,
raising concerns about effects of these pharmaceuticals in non-target organisms.
In this study, we hypothesized that the toxicity of a pharmaceutical towards a
non-target invertebrate depends on the presence of the human drug target
orthologs in this species. This was tested by assessing toxicity of
pharmaceuticals with (miconazole and promethazine) and without (levonorgestrel)
identified drug target orthologs in the cladoceran Daphnia magna. The toxicity
was evaluated using general toxicity endpoints at individual (immobility,
reproduction and development), biochemical (RNA and DNA content) and molecular
(gene expression) levels. The results provide evidence for higher toxicity of
miconazole and promethazine, i.e. the drugs with identified drug target
orthologs. At the individual level, miconazole had the lowest effect
concentrations for immobility and reproduction (0.3 and 0.022 mg L-1,
respectively) followed by promethazine (1.6 and 0.18 mg L-1, respectively). At
the biochemical level, individual RNA content was affected by miconazole and
promethazine already at 0.0023 and 0.059 mg L-1, respectively. At the molecular
level, gene expression for cuticle protein was significantly suppressed by
exposure to both miconazole and promethazine; moreover, daphnids exposed to
miconazole had significantly lower vitellogenin expression. Levonorgestrel did
not have any effects on any endpoints in the concentrations tested. These results
highlight the importance of considering drug target conservation in environmental
risk assessments of pharmaceuticals.
PMID- 25140794
TI - Souroubea sympetala (Marcgraviaceae): a medicinal plant that exerts anxiolysis
through interaction with the GABAA benzodiazepine receptor.
AB - The mode of action of the anxiolytic medicinal plant Souroubea sympetala was
investigated to test the hypothesis that extracts and the active principle act at
the pharmacologically important GABAA-benzodiazepine (GABAA-BZD) receptor. Leaf
extracts prepared by ethyl acetate extraction or supercritical extraction,
previously determined to have 5.54 mg/g and 6.78 mg/g of the active principle,
betulinic acid, respectively, reduced behavioural parameters associated with
anxiety in a rat model. When animals were pretreated with the GABAA-BZD receptor
antagonist flumazenil, followed by the plant extracts, or a more soluble
derivative of the active principle, the methyl ester of betulinic acid (MeBA),
flumazenil eliminated the anxiety-reducing effect of plant extracts and MeBA,
demonstrating that S. sympetala acts via an agonist action on the GABAA-BZD
receptor. An in vitro GABAA-BZD competitive receptor binding assay also
demonstrated that S. sympetala extracts have an affinity for the GABAA-BZD
receptor, with an EC50 value of 123 MUg/mL (EtOAc leaf extract) and 154 MUg/mL
(supercritical CO2 extract). These experiments indicate that S. sympetala acts at
the GABAA-BZD receptor to elicit anxiolysis.
PMID- 25140793
TI - Proteomics analysis of amyloid and nonamyloid prion disease phenotypes reveals
both common and divergent mechanisms of neuropathogenesis.
AB - Prion diseases are a heterogeneous group of neurodegenerative disorders affecting
various mammals including humans. Prion diseases are characterized by a
misfolding of the host-encoded prion protein (PrP(C)) into a pathological isoform
termed PrP(Sc). In wild-type mice, PrP(C) is attached to the plasma membrane by a
glycosylphosphatidylinositol (GPI) anchor and PrP(Sc) typically accumulates in
diffuse nonamyloid deposits with gray matter spongiosis. By contrast, when mice
lacking the GPI anchor are infected with the same prion inoculum, PrP(Sc)
accumulates in dense perivascular amyloid plaques with little or no gray matter
spongiosis. In order to evaluate whether different host biochemical pathways were
implicated in these two phenotypically distinct prion disease models, we utilized
a proteomics approach. In both models, infected mice displayed evidence of a
neuroinflammatory response and complement activation. Proteins involved in cell
death and calcium homeostasis were also identified in both phenotypes. However,
mitochondrial pathways of apoptosis were implicated only in the nonamyloid form,
whereas metal binding and synaptic vesicle transport were more disrupted in the
amyloid phenotype. Thus, following infection with a single prion strain, PrP(C)
anchoring to the plasma membrane correlated not only with the type of PrP(Sc)
deposition but also with unique biochemical pathways associated with
pathogenesis.
PMID- 25140795
TI - Macular Changes Correlate with the Degree of Acute Anterior Uveitis in Patients
with Spondyloarthropathy.
AB - PURPOSE: To evaluate the correlation between anterior chamber inflammation and
the central foveal thickness of the retina in a homogenous uveitic group
(seronegative spondyloarthropathy (subgroup: ankylosing spondylitis)) of patients
with the first acute anterior unilateral uveitic attack. METHODS: Central foveal
thickness (FT) and perifoveal retinal thickness were recorded by optical
coherence tomography (Optovue RTVue-100), and the difference between the two eyes
was calculated. Statistical analysis was performed by Mathworks Matlab software.
Anterior chamber inflammation was measured by laser flare photometry (Kowa FM
600). RESULTS: A statistically significant (p < .05) increase was found in
retinal thickness in all OCT subfields in acute anterior uveitic eyes compared to
healthy fellow eyes. There was a linear correlation between the degree of
inflammation (laser flare photometry values) and central foveal thickness (r =
.900, p < .001). CONCLUSIONS: We could demonstrate close correlation between
macular thickness and inflammation in anterior uveitic patients with
spondyloarthropathy.
PMID- 25140796
TI - Functional roles of the dimer-interface residues in human ornithine
decarboxylase.
AB - Ornithine decarboxylase (ODC) catalyzes the decarboxylation of ornithine to
putrescine and is the rate-limiting enzyme in the polyamine biosynthesis pathway.
ODC is a dimeric enzyme, and the active sites of this enzyme reside at the dimer
interface. Once the enzyme dissociates, the enzyme activity is lost. In this
paper, we investigated the roles of amino acid residues at the dimer interface
regarding the dimerization, protein stability and/or enzyme activity of ODC. A
multiple sequence alignment of ODC and its homologous protein antizyme inhibitor
revealed that 5 of 9 residues (residues 165, 277, 331, 332 and 389) are
divergent, whereas 4 (134, 169, 294 and 322) are conserved. Analytical
ultracentrifugation analysis suggested that some dimer-interface amino acid
residues contribute to formation of the dimer of ODC and that this dimerization
results from the cooperativity of these interface residues. The quaternary
structure of the sextuple mutant Y331S/Y389D/R277S/D332E/V322D/D134A was changed
to a monomer rather than a dimer, and the Kd value of the mutant was 52.8 uM,
which is over 500-fold greater than that of the wild-type ODC (ODC_WT). In
addition, most interface mutants showed low but detectable or negligible enzyme
activity. Therefore, the protein stability of these interface mutants was
measured by differential scanning calorimetry. These results indicate that these
dimer-interface residues are important for dimer formation and, as a consequence,
are critical for enzyme catalysis.
PMID- 25140798
TI - A comparative study on in vitro osteogenic priming potential of electron spun
scaffold PLLA/HA/Col, PLLA/HA, and PLLA/Col for tissue engineering application.
AB - A comparative study on the in vitro osteogenic potential of electrospun poly-L
lactide/hydroxyapatite/collagen (PLLA/HA/Col, PLLA/HA, and PLLA/Col) scaffolds
was conducted. The morphology, chemical composition, and surface roughness of the
fibrous scaffolds were examined. Furthermore, cell attachment, distribution,
morphology, mineralization, extracellular matrix protein localization, and gene
expression of human mesenchymal stromal cells (hMSCs) differentiated on the
fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA were also analyzed. The
electrospun scaffolds with a diameter of 200-950 nm demonstrated well-formed
interconnected fibrous network structure, which supported the growth of hMSCs.
When compared with PLLA/H%A and PLLA/Col scaffolds, PLLA/Col/HA scaffolds
presented a higher density of viable cells and significant upregulation of genes
associated with osteogenic lineage, which were achieved without the use of
specific medium or growth factors. These results were supported by the elevated
levels of calcium, osteocalcin, and mineralization (P<0.05) observed at different
time points (0, 7, 14, and 21 days). Furthermore, electron microscopic
observations and fibronectin localization revealed that PLLA/Col/HA scaffolds
exhibited superior osteoinductivity, when compared with PLLA/Col or PLLA/HA
scaffolds. These findings indicated that the fibrous structure and synergistic
action of Col and nano-HA with high-molecular-weight PLLA played a vital role in
inducing osteogenic differentiation of hMSCs. The data obtained in this study
demonstrated that the developed fibrous PLLA/Col/HA biocomposite scaffold may be
supportive for stem cell based therapies for bone repair, when compared with the
other two scaffolds.
PMID- 25140799
TI - miR-203 suppresses the proliferation and migration and promotes the apoptosis of
lung cancer cells by targeting SRC.
AB - SRC, also known as proto-oncogene c-Src, is a non-receptor tyrosine kinase that
plays an important role in cancer progression by promoting survival,
angiogenesis, proliferation, and invasion pathways. In this study, we found that
SRC protein levels were consistently upregulated in lung cancer tissues, but that
SRC mRNA levels varied randomly, suggesting that a post-transcriptional mechanism
was involved in SRC regulation. Because microRNAs (miRNAs) are powerful post
transcriptional regulators of gene expression, we used bioinformatic analyses to
search for miRNAs that potentially target SRC. We identified specific targeting
sites for miR-203 in the 3'-untranslated region (3'-UTR) of SRC. We then
experimentally validated miR-203 as a direct regulator of SRC using cell
transfection and luciferase assays and showed that miR-203 inhibited SRC
expression and consequently triggered suppression of the SRC/Ras/ERK pathway.
Finally, we demonstrated that the repression of SRC by miR-203 suppressed the
proliferation and migration and promoted the apoptosis of lung cancer cells. In
summary, this study provides the first clues regarding the role of miR-203 as a
tumor suppressor in lung cancer cells through the inhibition of SRC translation.
PMID- 25140800
TI - Photodynamic therapy using systemic administration of 5-aminolevulinic acid and a
410-nm wavelength light-emitting diode for methicillin-resistant Staphylococcus
aureus-infected ulcers in mice.
AB - Bacterial resistance to antibiotics has become a worldwide problem. One potential
alternative for bacterial control is photodynamic therapy. 5-aminolevulinic acid
is a natural precursor of the photosensitizer protoporphyrin IX. Relatively
little is known about the antibacterial efficacy of photodynamic therapy using
the systemic administration of 5-aminolevulinic acid; a few reports have shown
that 5-aminolevulinic acid exerts photodynamic effects on methicillin-resistant
Staphylococcus aureus (MRSA) in vitro. In this study, we evaluated the
effectiveness of photodynamic therapy using 5-aminolevulinic acid and a 410-nm
wavelength light-emitting diode in vitro and in vivo for the treatment of MRSA.
We found that 5-aminolevulinic acid photodynamic therapy with the light-emitting
diode had an in-vitro bactericidal effect on MRSA. In vivo, protoporphyrin IX
successfully accumulated in MRSA on ulcer surfaces after intraperitoneal
administration of 5-aminolevulinic acid to mice. Furthermore, 5-aminolevulinic
acid photodynamic therapy accelerated wound healing and decreased bacterial
counts on ulcer surfaces; in contrast, vancomycin treatment did not accelerate
wound healing. Our findings indicate that 5-aminolevulinic acid photodynamic
therapy may be a new treatment option for MRSA-infected wounds.
PMID- 25140801
TI - Retention of habitat complexity minimizes disassembly of reef fish communities
following disturbance: a large-scale natural experiment.
AB - High biodiversity ecosystems are commonly associated with complex habitats. Coral
reefs are highly diverse ecosystems, but are under increasing pressure from
numerous stressors, many of which reduce live coral cover and habitat complexity
with concomitant effects on other organisms such as reef fishes. While previous
studies have highlighted the importance of habitat complexity in structuring reef
fish communities, they employed gradient or meta-analyses which lacked a
controlled experimental design over broad spatial scales to explicitly separate
the influence of live coral cover from overall habitat complexity. Here a natural
experiment using a long term (20 year), spatially extensive (~ 115,000 kms(2))
dataset from the Great Barrier Reef revealed the fundamental importance of
overall habitat complexity for reef fishes. Reductions of both live coral cover
and habitat complexity had substantial impacts on fish communities compared to
relatively minor impacts after major reductions in coral cover but not habitat
complexity. Where habitat complexity was substantially reduced, species
abundances broadly declined and a far greater number of fish species were locally
extirpated, including economically important fishes. This resulted in decreased
species richness and a loss of diversity within functional groups. Our results
suggest that the retention of habitat complexity following disturbances can
ameliorate the impacts of coral declines on reef fishes, so preserving their
capacity to perform important functional roles essential to reef resilience.
These results add to a growing body of evidence about the importance of habitat
complexity for reef fishes, and represent the first large-scale examination of
this question on the Great Barrier Reef.
PMID- 25140802
TI - Reducing Igf-1r levels leads to paradoxical and sexually dimorphic effects in HD
mice.
AB - Many of the neurodegenerative diseases that afflict people in later life are
associated with the formation of protein aggregates. These so-called
"proteinopathies" include Alzheimer's disease (AD) and Huntington's disease (HD).
The insulin/insulin-like growth factor signalling (IIS) pathway has been proposed
to modulate such diseases in model organisms, as well as the general ageing
process. In this pathway, insulin-like growth factor binds to insulin-like growth
factor receptors, such as the insulin-like growth factor 1 receptor (IGF-1R).
Heterozygous deletion of Igf-1r has been shown to lead to increased lifespan in
mice. Reducing the activity of this pathway had benefits in a HD C. elegans
model, and some of these may be attributed to the expected inhibition of mTOR
activity resulting in an increase in autophagy, which would enhance mutant
huntingtin clearance. Thus, we tested if heterozygous deletion of Igf-1r would
lead to benefits in HD related phenotypes in the mouse. Surprisingly, reducing
Igf-1r levels led to some beneficial effects in HD females, but also led to some
detrimental effects in HD males. Interestingly, Igf-1r deficiency had no
discernible effects on downstream mTOR signalling in HD mice. These results do
not support a broad beneficial effect of diminishing the IIS pathway in HD
pathology in a mammalian system.
PMID- 25140805
TI - High-throughput screening system to identify small molecules that induce
internalization and degradation of HER2.
AB - Overexpression of growth factor receptors in cancers, e.g., human epidermal
growth factor receptor 2 (HER2) in ovarian and breast cancers, is associated with
aggressiveness. A possible strategy to treat cancers that overexpress those
receptors is blockade of receptor signaling by inducing receptor internalization
and degradation. In this study, we developed a cell-based high-throughput
screening (HTS) system to identify small molecules that induce HER2
internalization by employing our recently developed acidic-pH-activatable probe
in combination with protein labeling technology. Our HTS system enabled facile
and reliable quantification of HER2 internalization with a Z' factor of 0.66 and
a signal-to-noise ratio of 44.6. As proof of concept, we used the system to
screen a ~155,000 small-molecule library and identified three hits that induced
HER2 internalization and degradation via at least two distinct mechanisms. This
HTS platform should be adaptable to other disease-related receptors in addition
to HER2.
PMID- 25140804
TI - In vivo efficacy of a synthetic coumarin derivative in a murine model of
aspergillosis.
AB - Despite advances in therapeutic modalities, aspergillosis remains a leading cause
of mortality. This has necessitated the identification of effective and safe
antifungal molecules. In the present study, in vivo safety and antifungal
efficacy of a coumarin derivative, N, N, N-Triethyl-11-(4-methyl-2-oxo-2H
benzopyran-7-yloxy)-11-oxoundecan-1-aminium bromide (SCD-1), was investigated.
The maximum tolerable dose of compound was determined according to OECD 423
guidelines. The compound could be assigned to category IV of the Globally
Harmonized System and its LD50 cut-off was found to be 2000 mg/kg body weight.
The survival increased in Aspergillus fumigatus-infected mice treated with a dose
of 200 mg/kg, orally or 100 mg/kg body weight, intraperitoneally, of SCD-1 in
comparison to infected-untreated animals. The SCD-1 treatment resulted in
significant reduction in colony counts in vital organs of the animals. Its
protective effect was also observed on day 14 as there was marked reduction in
fungal colonies. The treatment with SCD-1 also reduced the levels of serum
biochemical parameters with respect to infected-untreated animals. It could be
concluded that SCD-1 is a quite safe antifungal compound, which conferred dose
dependent protection against experimental aspergillosis. Therefore, SCD-1 holds
potential for developing new formulations for aspergillosis.
PMID- 25140803
TI - Cellular membrane accommodation to thermal oscillations in the coral Seriatopora
caliendrum.
AB - In the present study, the membrane lipid composition of corals from a region with
tidally induced upwelling was investigated. The coral community is subject to
strong temperature oscillations yet flourishes as a result of adaptation.
Glycerophosphocholine profiling of the dominant pocilloporid coral, Seriatopora
caliendrum, was performed using a validated method. The coral inhabiting the
upwelling region shows a definite shift in the ratio of lipid molecular species,
covering several subclasses. Mainly, the coral possesses a higher percentage of
saturated, monounsaturated and polyunsaturated plasmanylcholines and a lower
percentage of polyunsaturated phosphatidylcholines. Higher levels of lyso
plasmanylcholines containing saturated or monounsaturated fatty acid chains were
also revealed in coral tissue at the distal portion of the branch. Based on the
physicochemical properties of these lipids, we proposed mechanisms for handling
cellular membrane perturbations, such as tension, induced by thermal oscillation
to determine how coral cells are able to spontaneously maintain their
physiological functions, in both molecular and physical terms. Interestingly, the
biochemical and biophysical properties of these lipids also have beneficial
effects on the resistance, maintenance, and growth of the corals. The results of
this study suggest that lipid metabolic adjustment is a major factor in the
adaption of S. caliendrum in upwelling regions.
PMID- 25140806
TI - The perioperative management of patients undergoing combined heart-liver
transplantation.
AB - BACKGROUND: Combined heart-liver transplantation (CHLT) is an uncommonly
performed procedure for patients with coexisting cardiac and liver disease.
METHODS: A retrospective review was performed of patients undergoing CHLT at our
institution from 1999 to 2013. Information related to preoperative organ
function, intraoperative management, surgical approach, transfusions,
postoperative findings, and 30-day mortality was reviewed. RESULTS: Twenty-seven
CHLT were performed, with 4 of the 27 including simultaneous kidney
transplantation. Familial amyloidosis was the indication for 21 CHLTs (78%), and
12 of these explanted livers were used for domino transplantations. Nineteen
patients (70%) were receiving inotropic infusions at the time of organ
availability. Median preoperative model for end-stage liver disease score was 12.
Liver transplantation immediately preceded cardiac transplantation in 2 of the 27
cases because of the presence of high titer donor-specific antibodies and the
potential of the liver to lead to a reduction in the antibody titer. Venovenous
bypass was used in 14 operations (52%) which were performed with the caval
interposition approach to liver transplantation, cardiopulmonary bypass during
liver transplantation in two cases (7%), and no bypass in 11 operations (41%)
performed with caval sparing (piggyback) surgical technique. Postoperatively,
median duration of mechanical ventilation, intensive care unit stay, and hospital
stay until discharge were 1 day, 5.5 days, and 15 days, respectively.
Transfusions in the first 48 hr after CHLT were not substantial in most patients.
One patient died within 30 days of CHLT. CONCLUSION: Combined heart-liver
transplantation is a life-saving operation that is performed with relatively low
mortality and can be successfully performed in select patients with congenital or
acquired cardiac disease.
PMID- 25140807
TI - Diet and human mobility from the lapita to the early historic period on Uripiv
island, Northeast Malakula, Vanuatu.
AB - Vanuatu was first settled ca. 3000 years ago by populations associated with the
Lapita culture. Models of diet, subsistence practices, and human interaction for
the Lapita and subsequent occupation periods have been developed mainly using the
available archaeological and paleoenvironmental data. We test these models using
stable (carbon, nitrogen, and sulfur) and radiogenic (strontium) isotopes to
assess the diet and childhood residency of past communities that lived on the
small (<1 km2) island of Uripiv, located off the northeast coast of Malakula,
Vanuatu. The burials are from the initial Lapita occupation of the island (ca.
2800-2600 BP), the subsequent later Lapita (LL, ca. 2600-2500 BP) and post-Lapita
(PL, ca. 2500-2000 BP) occupations, in addition to a late prehistoric/historic
(LPH, ca. 300-150 BP) occupation period. The human stable isotope results
indicate a progressively more terrestrial diet over time, which supports the
archaeological model of an intensification of horticultural and arboricultural
systems as local resources were depleted, populations grew, and cultural
situations changed. Pig diets were similar and included marine foods during the
Lapita and PL periods but were highly terrestrial during the LPH period. This
dietary pattern indicates that there was little variation in animal husbandry
methods during the first 800 years of prehistory; however, there was a subsequent
change as animal diets became more controlled in the LPH period. After comparison
with the local bioavailable 87Sr/86Sr baseline, all of the Lapita and LPH
individuals appeared to be 'local', but three of the PL individuals were
identified as "non-local." We suggest that these "non-locals" moved to the island
after infancy or childhood from one of the larger islands, supporting the model
of a high level of regional interaction during the post-Lapita period.
PMID- 25140809
TI - Urbanisation at multiple scales is associated with larger size and higher
fecundity of an orb-weaving spider.
AB - Urbanisation modifies landscapes at multiple scales, impacting the local climate
and changing the extent and quality of natural habitats. These habitat
modifications significantly alter species distributions and can result in
increased abundance of select species which are able to exploit novel ecosystems.
We examined the effect of urbanisation at local and landscape scales on the body
size, lipid reserves and ovary weight of Nephila plumipes, an orb weaving spider
commonly found in both urban and natural landscapes. Habitat variables at
landscape, local and microhabitat scales were integrated to create a series of
indexes that quantified the degree of urbanisation at each site. Spider size was
negatively associated with vegetation cover at a landscape scale, and positively
associated with hard surfaces and anthropogenic disturbance on a local and
microhabitat scale. Ovary weight increased in higher socioeconomic areas and was
positively associated with hard surfaces and leaf litter at a local scale. The
larger size and increased reproductive capacity of N.plumipes in urban areas show
that some species benefit from the habitat changes associated with urbanisation.
Our results also highlight the importance of incorporating environmental
variables from multiple scales when quantifying species responses to landscape
modification.
PMID- 25140810
TI - Synthesis of the erythrina alkaloid erysotramidine.
AB - A concise synthesis of erysotramidine (an alkaloid belonging to the erythrina
family) was achieved starting with an inexpensive phenol and amine derivative.
The synthesis is based on oxidative phenol dearomatizations mediated by a
hypervalent iodine reagent and includes a novel route to a key indolinone moiety.
PMID- 25140811
TI - Vascular O-GlcNAcylation augments reactivity to constrictor stimuli by prolonging
phosphorylated levels of the myosin light chain.
AB - O-GlcNAcylation is a modification that alters the function of numerous proteins.
We hypothesized that augmented O-GlcNAcylation levels enhance myosin light chain
kinase (MLCK) and reduce myosin light chain phosphatase (MLCP) activity, leading
to increased vascular contractile responsiveness. The vascular responses were
measured by isometric force displacement. Thoracic aorta and vascular smooth
muscle cells (VSMCs) from rats were incubated with vehicle or with PugNAc, which
increases O-GlcNAcylation. In addition, we determined whether proteins that play
an important role in the regulation of MLCK and MLCP activity are directly
affected by O-GlcNAcylation. PugNAc enhanced phenylephrine (PE) responses in rat
aortas (maximal effect, 14.2 +/- 2 vs 7.9 +/- 1 mN for vehicle, n=7). Treatment
with an MLCP inhibitor (calyculin A) augmented vascular responses to PE (13.4 +/-
2 mN) and abolished the differences in PE-response between the groups. The effect
of PugNAc was not observed when vessels were preincubated with ML-9, an MLCK
inhibitor (7.3 +/- 2 vs 7.5 +/- 2 mN for vehicle, n=5). Furthermore, our data
showed that differences in the PE-induced contractile response between the groups
were abolished by the activator of AMP-activated protein kinase (AICAR; 6.1 +/- 2
vs 7.4 +/- 2 mN for vehicle, n=5). PugNAc increased phosphorylation of myosin
phosphatase target subunit 1 (MYPT-1) and protein kinase C-potentiated inhibitor
protein of 17 kDa (CPI-17), which are involved in RhoA/Rho-kinase-mediated
inhibition of myosin phosphatase activity. PugNAc incubation produced a time
dependent increase in vascular phosphorylation of myosin light chain and
decreased phosphorylation levels of AMP-activated protein kinase, which decreased
the affinity of MLCK for Ca(2+)/calmodulin. Our data suggest that proteins that
play an important role in the regulation of MLCK and MLCP activity are directly
affected by O-GlcNAcylation, favoring vascular contraction.
PMID- 25140813
TI - Effects of bromopride on expression of metalloproteinases and interleukins in
left colonic anastomoses: an experimental study.
AB - Anastomotic dehiscence is the most severe complication of colorectal surgery.
Metalloproteinases (MMPs) and interleukins (ILs) can be used to analyze the
healing process of anastomosis. To evaluate the effects of bromopride on MMP and
cytokine gene expression in left colonic anastomoses in rats with or without
induced abdominal sepsis, 80 rats were divided into two groups for euthanasia on
the third or seventh postoperative day (POD). They were then divided into
subgroups of 20 rats for sepsis induction or not, and then into subgroups of 10
rats for administration of bromopride or saline. Left colonic anastomosis was
performed and abdominal sepsis was induced by cecal ligation and puncture. A
colonic segment containing the anastomosis was removed for analysis of gene
expression of MMP-1alpha, MMP-8, MMP-13, IL-beta, IL-6, IL-10, tumor necrosis
factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma). On the third POD,
bromopride was associated with increased MMP-1alpha, MMP-13, IL-6, IFN-gamma, and
IL-10 gene expression. On the seventh POD, all MMP transcripts became negatively
modulated and all IL transcripts became positively modulated. In the presence of
sepsis, bromopride administration increased MMP-8 and IFN-gamma gene expression
and decreased MMP-1, TNF-alpha, IL-6, and IL-10 gene expression on the third POD.
On the seventh POD, we observed increased expression of MMP-13 and all cytokines,
except for TNF-alpha. In conclusion, bromopride interferes with MMP and IL gene
expression during anastomotic healing. Further studies are needed to correlate
these changes with the healing process.
PMID- 25140812
TI - Pharmacological characterization of the relaxant effect induced by adrenomedullin
in rat cavernosal smooth muscle.
AB - The aim of the present study was to determine the mechanisms underlying the
relaxant effect of adrenomedullin (AM) in rat cavernosal smooth muscle (CSM) and
the expression of AM system components in this tissue. Functional assays using
standard muscle bath procedures were performed in CSM isolated from male Wistar
rats. Protein and mRNA levels of pre-pro-AM, calcitonin receptor-like receptor
(CRLR), and Subtypes 1, 2 and 3 of the receptor activity-modifying protein (RAMP)
family were assessed by Western immunoblotting and quantitative real-time
polymerase chain reaction, respectively. Nitrate and 6-keto-prostaglandin
F(1alpha) (6-keto-PGF(1alpha); a stable product of prostacyclin) levels were
determined using commercially available kits. Protein and mRNA of AM, CRLR, and
RAMP 1, -2, and -3 were detected in rat CSM. Immunohistochemical assays
demonstrated that AM and CRLR were expressed in rat CSM. AM relaxed CSM strips in
a concentration-dependent manner. AM(22-52), a selective antagonist for AM
receptors, reduced the relaxation induced by AM. Conversely, CGRP(8-37), a
selective antagonist for calcitonin gene-related peptide receptors, did not
affect AM-induced relaxation. Preincubation of CSM strips with N(G)-nitro-L
arginine-methyl-ester (L-NAME, nitric oxide synthase inhibitor), 1H
(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, quanylyl cyclase inhibitor), Rp-8
Br-PET-cGMPS (cGMP-dependent protein kinase inhibitor), SC560 [5-(4-chlorophenyl)
1-(4-methoxyphenyl)-3-trifluoromethyl pyrazole, selective cyclooxygenase-1
inhibitor], and 4-aminopyridine (voltage-dependent K(+) channel blocker) reduced
AM-induced relaxation. On the other hand, 7-nitroindazole (selective neuronal
nitric oxide synthase inhibitor), wortmannin (phosphatidylinositol 3-kinase
inhibitor), H89 (protein kinase A inhibitor), SQ22536 [9-(tetrahydro-2-furanyl)
9H-purin-6-amine, adenylate cyclase inhibitor], glibenclamide (selective blocker
of ATP-sensitive K(+) channels), and apamin (Ca(2+)-activated channel blocker)
did not affect AM-induced relaxation. AM increased nitrate levels and 6-keto
PGF1alpha in rat CSM. The major new contribution of this research is that it
demonstrated expression of AM and its receptor in rat CSM. Moreover, we provided
evidence that AM-induced relaxation in this tissue is mediated by AM receptors by
a mechanism that involves the nitric oxide-cGMP pathway, a vasodilator
prostanoid, and the opening of voltage-dependent K(+) channels.
PMID- 25140814
TI - Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic
encephalopathy.
AB - The aim of this study was to analyze the association of different clinical
contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A
total of 110 children with hypoxic-ischemic encephalopathy and 128 control
children were selected for this study. Association of gender, gestational age,
birth weight, Apgar score, cranial ultrasonography, and magnetic resonance
imaging findings with genotypic data of six haplotype-tagging single nucleotide
polymorphisms and the most commonly investigated rs1800779 and rs2070744
polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and
rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy.
Children with the TGT haplotype were infants below 32 weeks of gestation and they
had the most severe brain damage. Increased incidence of the TT genotype of the
NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy
patients with medium and severe brain damage. The probability of brain damage was
twice as high in children with the TT genotype than in children with the TG
genotype of the same polymorphism. Furthermore, the T allele of the same
polymorphism was twice as frequent in children with lower Apgar scores. This
study strongly suggests associations of NOS3 gene polymorphism with intensity of
brain damage and severity of the clinical picture in affected children.
PMID- 25140815
TI - Effects of immobilization and remobilization on the ankle joint in Wistar rats.
AB - A sprained ankle is a common musculoskeletal sports injury and it is often
treated by immobilization of the joint. Despite the beneficial effects of this
therapeutic measure, the high prevalence of residual symptoms affects the quality
of life, and remobilization of the joint can reverse this situation. The aim of
this study was to analyze the effects of immobilization and remobilization on the
ankle joint of Wistar rats. Eighteen male rats had their right hindlimb
immobilized for 15 days, and were divided into the following groups: G1,
immobilized; G2, remobilized freely for 14 days; and G3, remobilized by swimming
and jumping in water for 14 days, performed on alternate days, with progression
of time and a series of exercises. The contralateral limb was the control. After
the experimental period, the ankle joints were processed for microscopic
analysis. Histomorphometry did not show any significant differences between the
control and immobilized/remobilized groups and members, in terms of number of
chondrocytes and thickness of the articular cartilage of the tibia and talus.
Morphological analysis of animals from G1 showed significant degenerative lesions
in the talus, such as exposure of the subchondral bone, flocculation, and cracks
between the anterior and mid-regions of the articular cartilage and the synovial
membrane. Remobilization by therapeutic exercise in water led to recovery in the
articular cartilage and synovial membrane of the ankle joint when compared with
free remobilization, and it was shown to be an effective therapeutic measure in
the recovery of the ankle joint.
PMID- 25140816
TI - A forced running wheel system with a microcontroller that provides high-intensity
exercise training in an animal ischemic stroke model.
AB - We developed a forced non-electric-shock running wheel (FNESRW) system that
provides rats with high-intensity exercise training using automatic exercise
training patterns that are controlled by a microcontroller. The proposed system
successfully makes a breakthrough in the traditional motorized running wheel to
allow rats to perform high-intensity training and to enable comparisons with the
treadmill at the same exercise intensity without any electric shock. A polyvinyl
chloride runway with a rough rubber surface was coated on the periphery of the
wheel so as to permit automatic acceleration training, and which allowed the rats
to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke
model was used to validate the proposed system. FNESRW, treadmill, control, and
sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of
endurance running training. After 3 weeks, the experiments of middle cerebral
artery occlusion, the modified neurological severity score (mNSS), an inclined
plane test, and triphenyltetrazolium chloride were performed to evaluate the
effectiveness of the proposed platform. The proposed platform showed that
enhancement of motor function, mNSS, and infarct volumes was significantly
stronger in the FNESRW group than the control group (P<0.05) and similar to the
treadmill group. The experimental data demonstrated that the proposed platform
can be applied to test the benefit of exercise-preconditioning-induced
neuroprotection using the animal stroke model. Additional advantages of the
FNESRW system include stand-alone capability, independence of subjective human
adjustment, and ease of use.
PMID- 25140817
TI - Dynamic expression of desmin, alpha-SMA and TGF-beta1 during hepatic fibrogenesis
induced by selective bile duct ligation in young rats.
AB - We previously described a selective bile duct ligation model to elucidate the
process of hepatic fibrogenesis in children with biliary atresia or intrahepatic
biliary stenosis. Using this model, we identified changes in the expression of
alpha smooth muscle actin (alpha-SMA) both in the obstructed parenchyma and in
the hepatic parenchyma adjacent to the obstruction. However, the expression
profiles of desmin and TGF-beta1, molecules known to be involved in hepatic
fibrogenesis, were unchanged when analyzed by semiquantitative polymerase chain
reaction (RT-PCR). Thus, the molecular mechanisms involved in the modulation of
liver fibrosis in this experimental model are not fully understood. This study
aimed to evaluate the molecular changes in an experimental model of selective
bile duct ligation and to compare the gene expression changes observed in RT-PCR
and in real-time quantitative PCR (qRT-PCR). Twenty-eight Wistar rats of both
sexes and weaning age (21-23 days old) were used. The rats were separated into
groups that were assessed 7 or 60 days after selective biliary duct ligation. The
expression of desmin, alpha-SMA and TGF-beta1 was examined in tissue from hepatic
parenchyma with biliary obstruction (BO) and in hepatic parenchyma without
biliary obstruction (WBO), using RT-PCR and qRT-PCR. The results obtained in this
study using these two methods were significantly different. The BO parenchyma had
a more severe fibrogenic reaction, with increased alpha-SMA and TGF-beta1
expression after 7 days. The WBO parenchyma presented a later, fibrotic response,
with increased desmin expression 7 days after surgery and increased alpha-SMA 60
days after surgery. The qRT-PCR technique was more sensitive to expression
changes than the semiquantitative method.
PMID- 25140820
TI - Phosphine complexes of aluminium(III) halides - preparation and structural and
spectroscopic systematics.
AB - Six-coordinate pseudo-octahedral complexes trans-[AlX2(L-L)2][AlX4] (X = Cl, Br
or I; L-L = o-C6H4(PMe2)2, Me2P(CH2)2PMe2) are produced from reaction of AlX3
with the diphosphine in CH2Cl2 (X = Cl) or toluene (X = Br or I) solution. Four
coordinate dimers [Cl3Al(MU-L'-L')AlCl3] (L'-L' = Me2P(CH2)2PMe2,
Cy2P(CH2)2PCy2), and the tetrahedral cation [AlCl2{o-C6H4(PPh2)2}][AlCl4] were
also obtained. Both four- and five-coordinate complexes [AlX3(PMe3)] and
[AlX3(PMe3)2] could be isolated with PMe3 depending upon the ratio of reagents
used. These extremely moisture sensitive complexes have been characterised by
microanalysis, IR and multinuclear NMR ((1)H, (31)P{(1)H} and (27)Al)
spectroscopy. X-ray crystal structures are reported for [AlCl2{o
C6H4(PMe2)2}2][AlCl4], [AlCl2{Me2P(CH2)2PMe2}2][AlCl4], [Cl3Al{MU
Me2P(CH2)2PMe2}AlCl3], [Cl3Al{MU-Cy2P(CH2)2PCy2}AlCl3], [AlCl3(PMe3)],
[AlCl3(PMe3)2], and for the six-coordinate cation complex [AlCl2{o
C6H4(PPh2)2}2][AlCl4], although a bulk sample of the last could not be isolated.
Tertiary arsines (AsPh3 or AsEt3) form only 1 : 1 complexes even with excess
arsine present. The unstable [AlCl2{o-C6H4(AsMe2)2}][AlCl4] is also described,
and shown to decompose rapidly in CH2Cl2 solution to form the diquaternised
diarsine cation [o-C6H4(AsMe2)2(CH2)][AlCl4]2, which was fully characterised.
Comparisons are drawn with the corresponding gallium(iii) systems (Cheng et al.,
Inorg. Chem., 2007, 46, 7215-7223) and with AlX3 complexes of Group 16 ligands
(George et al., Dalton Trans., 2014, 43, 3637-3648), and it is concluded that the
differences between the Al and Ga systems reflect the higher Lewis acidity of
aluminium(iii) towards soft donor ligands.
PMID- 25140819
TI - A continuous-flow C. elegans sorting system with integrated optical fiber
detection and laminar flow switching.
AB - We present a high-throughput continuous-flow C. elegans sorting device that works
based on integrated optical fiber detection and laminar flow switching. Two types
of genetically engineered nematodes are allowed to flow into the device and their
genotypes are detected based on their fluorescence, without the need for
immobilization, by integrated optical fibers. A novel dynamic fluidic switch
sorts the nematodes to desired outlets. By changing input pressures of the
control inlets, the laminar flow path is altered to steer the nematodes to
appropriate outlets. Compared to previously reported microfluidic C. elegans
sorting devices, sorting in this system is conducted in a continuous flow
environment without any immobilization technique or need for multilayer
mechanical valves to open and close the outlets. The continuous flow sorter not
only increases the throughput but also avoids any kind of invasive or possibly
damaging mechanical or chemical stimulus. We have characterized both the
detection and the switching accuracy of the sorting device at different flow
rates, and efficiencies approaching 100% can be achieved with a high throughput
of about one nematode per second. To confirm that there was no significant damage
to C. elegans following sorting, we recovered the sorted worms, finding no deaths
and no differences in behavior and propagation compared to control.
PMID- 25140818
TI - Synthesis of isocoumarins with different substituted patterns via Passerini-aldol
sequence.
AB - An efficient combination between the Passerini three-component reaction and aldol
condensation has been developed for the synthesis of bicyclic isocoumarins with
different substituted patterns via solvent-dependent domino pathways. These two
operationally friendly methods simultaneously install C-O and C-C bonds in a one
pot manner, allowing the utilization of low-cost and readily accessible 2
formylbenzoic acid, isocyanides, and arylglyoxals. Mechanisms of formation of
different substituted isocoumarin derivatives are also proposed.
PMID- 25140821
TI - Function and evolution of two forms of SecDF homologs in Streptomyces coelicolor.
AB - The general secretion (Sec) pathway plays a prominent role in bacterial protein
export, and the accessory component SecDF has been shown to improve
transportation efficiency. Inspection of Streptomyces coelicolor genome reveals
the unexpected presence of two different forms of secDF homologous genes: one in
fused form (secDF) and the other in separated form (secD and secF). However, the
functional role of two SecDF homologs in S. coelicolor has not yet been
determined. Transcriptional analysis of secDF homologs reveals that these genes
are constitutively expressed. However, the transcript levels of secD and secF are
much higher than that of secDF in S. coelicolor. Deletion of secDF or/and
secD/secF in S. coelicolor did result in reduced secretion efficiency of Xylanase
A and Amylase C, suggesting that they may have redundant functions for Sec
dependent translocation pathway. Moreover, our results also indicate that
SecD/SecF plays a more prominent role than SecDF in protein translocation.
Evolutionary analysis suggests that the fused and separated SecDF homologs in
Streptomyces may have disparate evolutionary ancestries. SecD/SecF may be
originated from vertical transmission of existing components from ancestor of
Streptomyces species. However, SecDF may be derived from bacterial ancestors
through horizontal gene transfer. Alternately, it is also plausible that SecDF
may have arisen through additional gene duplication and fusion events. The
acquisition of a second copy may confer a selective benefit to Streptomyces by
enhancing protein transport capacity. Taken together, our results provide new
insights into the potential biological function and evolutionary aspects of the
prokaryotic SecDF complex.
PMID- 25140822
TI - Nonlinear pedagogy: an effective approach to cater for individual differences in
learning a sports skill.
AB - Learning a sports skill is a complex process in which practitioners are
challenged to cater for individual differences. The main purpose of this study
was to explore the effectiveness of a Nonlinear Pedagogy approach for learning a
sports skill. Twenty-four 10-year-old females participated in a 4-week
intervention involving either a Nonlinear Pedagogy (i.e.,manipulation of task
constraints including equipment and rules) or a Linear Pedagogy (i.e.,
prescriptive, repetitive drills) approach to learn a tennis forehand stroke.
Performance accuracy scores, movement criterion scores and kinematic data were
measured during pre-intervention, post-intervention and retention tests. While
both groups showed improvements in performance accuracy scores over time, the
Nonlinear Pedagogy group displayed a greater number of movement clusters at post
test indicating the presence of degeneracy (i.e., many ways to achieve the same
outcome). The results suggest that degeneracy is effective for learning a sports
skill facilitated by a Nonlinear Pedagogy approach. These findings challenge the
common misconception that there must be only one ideal movement solution for a
task and thus have implications for coaches and educators when designing
instructions for skill acquisition.
PMID- 25140824
TI - Seeking small molecules for singlet fission: a heteroatom substitution strategy.
AB - We design theoretically small molecule candidates for singlet fission
chromophores, aiming to achieve a balance between sufficient diradical character
and kinetic persistence. We develop a perturbation strategy based on the
captodative effect to introduce diradical character into small pi-systems.
Specifically, this can be accomplished by replacing pairs of not necessarily
adjacent C atoms with isoelectronic and isosteric pairs of B and N atoms. Three
rules of thumb emerge from our studies to aid further design: (i) Lewis
structures provide insight into likely diradical character; (ii) formal radical
centers of the diradical must be well-separated; (iii) stabilization of radical
centers by a donor (N) and an acceptor (B) is essential. Following the rules, we
propose candidate molecules. Employing reliable multireference calculations for
excited states, we identify three likely candidate molecules for SF chromophores.
These include a benzene, a napthalene, and an azulene, where four C atoms are
replaced by a pair of B and a pair of N atoms.
PMID- 25140823
TI - HLA-B27 and human beta2-microglobulin affect the gut microbiota of transgenic
rats.
AB - The HLA-B27 gene is a major risk factor for clinical diseases including
ankylosing spondylitis, acute anterior uveitis, reactive arthritis, and psoriatic
arthritis, but its mechanism of risk enhancement is not completely understood.
The gut microbiome has recently been shown to influence several HLA-linked
diseases. However, the role of HLA-B27 in shaping the gut microbiome has not been
previously investigated. In this study, we characterize the differences in the
gut microbiota mediated by the presence of the HLA-B27 gene. We identified
differences in the cecal microbiota of Lewis rats transgenic for HLA-B27 and
human beta2-microglobulin (hbeta2m), compared with wild-type Lewis rats, using
biome representational in situ karyotyping (BRISK) and 16S rRNA gene sequencing.
16S sequencing revealed significant differences between transgenic animals and
wild type animals by principal coordinates analysis. Further analysis of the data
set revealed an increase in Prevotella spp. and a decrease in Rikenellaceae
relative abundance in the transgenic animals compared to the wild type animals.
By BRISK analysis, species-specific differences included an increase in
Bacteroides vulgatus abundance in HLA-B27/hbeta2m and hbeta2m compared to wild
type rats. The finding that HLA-B27 is associated with altered cecal microbiota
has not been shown before and can potentially provide a better understanding of
the clinical diseases associated with this gene.
PMID- 25140827
TI - The influence of a Te-depleted surface on the thermoelectric transport properties
of Bi2Te3 nanowires.
AB - We report on thermoelectric transport measurements along the basal plane of
several individual, single-crystalline Bi2Te3 nanowires (NWs) with different
cross-sectional areas, grown by a vapor-liquid-solid method. Lithographically
defined microdevices allowed us to determine the Seebeck coefficient S,
electrical conductivity sigma, and thermal conductivity kappa of individual NWs.
The NWs studied show near intrinsic transport properties with low electrical
conductivities of around sigma = (3.2 +/- 0.9) * 104 Omega-1 m-1 at room
temperature. We observe a transition of the Seebeck coefficient from positive to
negative values (S = +133 MUVK-1 to S = -87 MUVK-1) with increasing surface-to
volume ratio at room temperature, which can be explained by the presence of an
approximately 5 nm thick Te-depleted layer at the surface of the NWs. The thermal
conductivities of our NWs are in the range of kappa = (1.4 +/- 0.4) Wm-1 K-1 at
room temperature, which is lower than literature values for bulk Bi2Te3. We
attribute this suppression in thermal conductivity to enhanced scattering of
phonons at the surface of the NWs. Despite their reduced thermal conductivities,
the NWs investigated only show a moderate figure of merit between 0.02 and 0.18
due to their near intrinsic transport properties.
PMID- 25140825
TI - Targeted capture and heterologous expression of the Pseudoalteromonas
alterochromide gene cluster in Escherichia coli represents a promising natural
product exploratory platform.
AB - Marine pseudoalteromonads represent a very promising source of biologically
important natural product molecules. To access and exploit the full chemical
capacity of these cosmopolitan Gram-(-) bacteria, we sought to apply universal
synthetic biology tools to capture, refactor, and express biosynthetic gene
clusters for the production of complex organic compounds in reliable host
organisms. Here, we report a platform for the capture of proteobacterial gene
clusters using a transformation-associated recombination (TAR) strategy coupled
with direct pathway manipulation and expression in Escherichia coli. The ~34 kb
pathway for production of alterochromide lipopeptides by Pseudoalteromonas
piscicida JCM 20779 was captured and heterologously expressed in E. coli
utilizing native and E. coli-based T7 promoter sequences. Our approach enabled
both facile production of the alterochromides and in vivo interrogation of gene
function associated with alterochromide's unusual brominated lipid side chain.
This platform represents a simple but effective strategy for the discovery and
biosynthetic characterization of natural products from marine proteobacteria.
PMID- 25140828
TI - Structure, phase transition, and controllable thermal expansion behaviors of Sc(2
x)Fe(x)Mo3O12.
AB - The crystal structures, phase transition, and thermal expansion behaviors of
solid solutions of Sc(2-x)Fe(x)Mo3O12 (0 <= x <= 2) have been examined using X
ray diffraction (XRD), neutron powder diffraction (NPD), and differential
scanning calorimetry (DSC). At room temperature, samples crystallize in a single
orthorhombic structure for the compositions of x < 0.6 and monoclinic for x >=
0.6, respectively. DSC results indicate that the phase transition temperature
from monoclinic to orthorhombic structure is enhanced by increasing the Fe(3+)
content. High-temperature XRD and NPD results show that Sc(1.3)Fe(0.7)Mo3O12
exhibits near zero thermal expansion, and the volumetric coefficients of thermal
expansion derived from XRD and NPD are 0.28 * 10(-6) degrees C(-1) (250-800
degrees C) and 0.65 * 10(-6) degrees C(-1) (227-427 degrees C), respectively.
NPD results of Sc2Mo3O12 (x = 0) and Sc(1.3)Fe(0.7)Mo3O12 (x = 0.7) indicate that
Fe substitution for Sc induces reduction of the mean Sc(Fe)-Mo nonbond distance
and the different thermal variations of Sc(Fe)-O5-Mo2 and Sc(Fe)-O3-Mo2 bond
angles. The correlation between the displacements of oxygen atoms and the
variation of unit cell parameters was investigated in detail for Sc2Mo3O12.
PMID- 25140830
TI - Symptomatic spinal leptomeningeal metastasis from intracranial glioblastoma
multiforme.
PMID- 25140831
TI - Destabilization effect of transition metal fluorides on sodium borohydride.
AB - The effect of transition metal fluorides on the decomposition of NaBH4 has been
investigated for NaBH4 ball milled with TiF3, MnF3 or FeF3. The compounds were
examined by thermal programmed desorption with residual gas analysis, thermo
gravimetric analysis and volumetric measurements using a Sieverts-type apparatus.
The phase formation process during thermal decomposition was studied by in situ
synchrotron radiation powder X-ray diffraction on the as-milled powders. NaBF4
was among the products in all mechano-chemical reactions. (11)B-NMR spectra
analysis gave NaBF4 : NaBH4 ratios of 1 : 150 for Na-Ti, 1 : 40 for Na-Mn, and 1
: 10 for Na-Fe. Pure NaBH4 possessed a hydrogen release onset temperature of 430
degrees C. The hydrogen release in the NaBH4-MnF3 system began as low as 130
degrees C. FeF3 decreased the onset temperature to 161 degrees C and TiF3 to 200
degrees C. TiF3 reacted completely with NaBH4 below 320 degrees C. All the
examined systems have negligible emissions of diborane species. H-sorption
studies performed at selected temperatures above 300 degrees C exhibited
relatively fast desorption kinetics. Partial hydrogen re-absorption was observed
for the Na-Mn and Na-Fe samples.
PMID- 25140832
TI - Silver-catalysed direct amination of unactivated C-H bonds of functionalized
molecules.
AB - Carbon-nitrogen bond formation from inert C-H bonds is an ideal organic
transformation and a highly desirable method for the synthesis of N-containing
molecules due to its high efficiency and atom economy. In this report, we develop
a general reaction to achieve an unprecedented selective intramolecular amination
of unactivated C-H bond in the absence of complex directing groups.
Functionalized heterocyclic products are built up from readily available linear
amines through simple and reliable silver catalysis, representing a new silver
based C-H functionalization. This method displays preference for primary sp(3) C
H bonds and exhibits distinct chemo- and regioselectivity compared to existing
methods of direct amination (Hofmann-Loffler-Freytag reaction and nitrene
insertion). The study highlights the manipulation of unfunctionalized groups in
organic molecules to furnish complex structural units in the natural and
bioactive molecules.
PMID- 25140833
TI - c-CBL E3 ubiquitin ligase is overexpressed in cutaneous T-cell lymphoma: its
inhibition promotes activation-induced cell death.
AB - Mycosis fungoides and Sezary syndrome are two major forms of cutaneous T-cell
lymphoma (CTCL) characterized by resistance to apoptosis. A central pathway for T
cell apoptosis is activation-induced cell death, which is triggered through the T
cell receptor (TCR). This results in upregulation of FAS ligand (FASL) and
subsequent apoptosis through the FAS death receptor pathway. It has been known
for more than a decade that TCR signaling is defective in CTCL; however, the
underlying mechanism has not been apparent. In this report, we show that the E3
ubiquitin ligase, c-CBL, is overexpressed in CTCL and that its knockdown
overcomes defective TCR signaling, resulting in phosphorylation of PLC-g1,
calcium influx, ROS generation, upregulation of FASL, and extrinsic pathway
apoptosis in CTCL cells expressing adequate FAS. In CTCL cells with suboptimal
FAS expression, FAS can be upregulated epigenetically by derepression of the FAS
promoter using methotrexate, which we showed previously has activity as a DNA
methylation inhibitor. Using these combined strategies, FAS-low as well as FAS
high CTCL cells can be killed effectively.
PMID- 25140834
TI - Prussian blue-Au nanocomposites actuated hemin/G-quadruplexes catalysis for
amplified detection of DNA, Hg2+ and adenosine triphosphate.
AB - In this paper, horseradish peroxidase-mimicking DNAzyme (HRP-DNAzyme) and
Prussian blue (PB)-gold (Au) nanocomposites were designed as versatile
electrochemical sensing platforms for the amplified detection of DNA, Hg(2+) and
adenosine triphosphate (ATP). By the conjugation of the target probe with the
capture probe, a conformational change resulted in the formation of HRP-DNAzyme
on the PB-Au modified electrode. The redox of HRP-DNAzyme (red) was efficiently
carried out in the presence of H2O2, in which PB acted as a mediator stimulating
the biocatalytic functions of HRP-DNAzyme and actuated a catalytic cycle bringing
an amplified signal. Specific recognition of the target DNA, Hg(2+) and ATP
allowed selective amperometric detection of the target molecule. The detection
limits of DNA, Hg(2+) and ATP were 50 nM, 30 pM and 3 nM, respectively. The
highlight of this work is that the catalytic cycle between PB-Au nanocomposites
and HRP-DNAzyme was adequately utilized in the amplification platform for
versatile sensing. The novel electrocatalytic biosensor involving only one-step
incubation exhibited a wide linear range, low detection limit, and satisfactory
selectivity and operational stability. The proposed approach provided an ease-of
use and universal reporting system with a simple design and easy operations.
PMID- 25140835
TI - A Nile Red/BODIPY-based bimodal probe sensitive to changes in the micropolarity
and microviscosity of the endoplasmic reticulum.
AB - We herein report a fluorescent bimodal probe (1) capable of determining ER
viscosity and polarity changes using FLIM and fluorescence ratiometry,
respectively; during ER stress caused by tunicamycin, the viscosity was increased
from ca. 129.5 to 182.0 cP and the polarity of the ER (dielectric constant,
epsilon) enhanced from 18.5 to 21.1.
PMID- 25140836
TI - Effect of drainage on postoperative pain after laparoscopic ovarian cystectomy.
AB - The aim of this prospective study was to investigate the effect of drainage on
postoperative shoulder and abdominal pain after uncomplicated laparoscopic
ovarian cystectomy (LOC). Allocation to drain or not to drain was non-randomised.
There were 55 patients with drainage and 56 patients without drainage.
Postoperative shoulder and abdominal pain was assessed using a 10-point visual
analogue scale. Postoperative hospital stay in the drainage group was longer than
the non-drainage group (p = 0.040). Postoperative shoulder pain scores at 6 h and
24 h were similar between the drainage and non-drainage groups (p = 0.376 and p =
0.847, respectively). Postoperative abdominal pain was higher in the drainage
group at 6 h (p = 0.009), but was similar at 24 h (p = 0.097) between the groups.
These data suggest that for LOC, drainage may not be useful to prevent
postoperative shoulder pain and also increases postoperative abdominal pain and
length of hospital stay.
PMID- 25140838
TI - Synthesis of Au-decorated V2O5@ZnO heteronanostructures and enhanced plasmonic
photocatalytic activity.
AB - A ternary plasmonic photocatalyst consisting of Au-decorated V2O5@ZnO
heteronanorods was successfully fabricated by an innovative four-step process:
thermal evaporation of ZnO powders, CVD of intermediate on ZnO, solution
deposition of Au NPs, and final thermal oxidization. SEM, TEM, EDX, XPS, and XRD
analyses revealed that the interior cores and exterior shells of the as-prepared
heteronanorods were single-crystal wurtzite-type ZnO and polycrystalline
orthorhombic V2O5, respectively, with a large quantity of Au NPs inlaid in the
V2O5 shell. The optical properties of the ternary photocatalyst were investigated
in detail and compared with those of bare ZnO and V2O5@ZnO. UV-vis absorption
spectra of ZnO, V2O5@ZnO, and Au-decorated V2O5@ZnO showed gradually enhanced
absorption in the visible region. In addition, gradually decreased emission
intensity was also observed in the photoluminescence (PL) spectra, revealing
enhanced charge separation efficiency. Because of these excellent qualities, the
photocatalytic behavior of the ternary photocatalyst was studied in the
photodegradation of methylene blue under UV-vis irradiation, which showed an
enhanced photodegradation rate nearly 7 times higher than that of bare ZnO and
nearly 3 times higher than that of V2O5@ZnO, mainly owing to the enlarged light
absorption region, the effective electron-hole separation at the V2O5-ZnO and
V2O5-Au interfaces, and strong localization of plasmonic near-field effects.
PMID- 25140837
TI - The parametric g-formula for time-to-event data: intuition and a worked example.
AB - BACKGROUND: The parametric g-formula can be used to estimate the effect of a
policy, intervention, or treatment. Unlike standard regression approaches, the
parametric g-formula can be used to adjust for time-varying confounders that are
affected by prior exposures. To date, there are few published examples in which
the method has been applied. METHODS: We provide a simple introduction to the
parametric g-formula and illustrate its application in an analysis of a small
cohort study of bone marrow transplant patients in which the effect of treatment
on mortality is subject to time-varying confounding. RESULTS: Standard regression
adjustment yields a biased estimate of the effect of treatment on mortality
relative to the estimate obtained by the g-formula. CONCLUSIONS: The g-formula
allows estimation of a relevant parameter for public health officials: the change
in the hazard of mortality under a hypothetical intervention, such as reduction
of exposure to a harmful agent or introduction of a beneficial new treatment. We
present a simple approach to implement the parametric g-formula that is
sufficiently general to allow easy adaptation to many settings of public health
relevance.
PMID- 25140839
TI - Genipin cross-linked nanocomposite films for the immobilization of antimicrobial
agent.
AB - Cellulose nanocrystal (CNC) reinforced chitosan based antimicrobial films were
prepared by immobilizing nisin on the surface of the films. Nanocomposite films
containing 18.65 MUg/cm(2) of nisin reduced the count of L. monocytogenes by 6.73
log CFU/g, compared to the control meat samples (8.54 log CFU/g) during storage
at 4 degrees C in a Ready-To-Eat (RTE) meat system. Film formulations containing
9.33 MUg/cm(2) of nisin increased the lag phase of L. monocytogenes on meat by
more than 21 days, whereas formulations with 18.65 MUg/cm(2) completely inhibited
the growth of L. monocytogenes during storage. Genipin was used to cross-link and
protect the activity of nisin during storage. Nanocomposite films cross-linked
with 0.05% w/v genipin exhibited the highest bioactivity (10.89 MUg/cm(2)) during
the storage experiment, as compared to that of the un-cross-linked films (7.23
MUg/cm(2)). Genipin cross-linked films were able to reduce the growth rate of L.
monocytogenes on ham samples by 21% as compared to the un-cross-linked films.
Spectroscopic analysis confirmed the formation of genipin-nisin-chitosan
heterocyclic cross-linked network. Genipin cross-linked films also improved the
swelling, water solubility, and mechanical properties of the nanocomposite films.
PMID- 25140840
TI - Stress and resilience in military mortuary workers: care of the dead from
battlefield to home.
AB - The death of a military service member in war provokes feelings of distress and
pride in mortuary workers who process the remains. To further understand their
reactions, the authors interviewed 34 military and civilian personnel to learn
more about their work stresses and rewards. They review stresses of anticipation,
exposure, and experience in handling the dead and explore the personal,
supervisory, and leadership strategies to reduce negative effects and promote
personal growth. These results can be applied to many other situations requiring
planning, implementing, and supervising mortuary operations involving mass death.
PMID- 25140842
TI - Reconstructing fungal natural product biosynthetic pathways.
AB - Large scale fungal genome sequencing has revealed a multitude of potential
natural product biosynthetic pathways that remain uncharted. Here we describe
some of the methods that have been used to explore them via heterologous gene
expression. We focus on filamentous fungal hosts and discuss the technological
challenges and successes behind the reconstruction of fungal natural product
pathways. Optimised, efficient heterologous expression of reconstructed
biosynthetic pathways promises progress in the discovery of novel compounds that
could be utilised by the pharmaceutical and agrochemical industries.
PMID- 25140844
TI - Managing corneal abrasions in primary care.
AB - Corneal abrasion is a common eye injury that occurs in all age-groups. A focused
history and physical exam can identify patients with corneal abrasions and
improve intervention time. Minor corneal abrasions usually heal within 48 hours
without complications or eye damage.
PMID- 25140843
TI - Does prenatal exposure to vitamin D-fortified margarine and milk alter birth
weight? A societal experiment.
AB - The present study examined whether exposure to vitamin D from fortified margarine
and milk during prenatal life influenced mean birth weight and the risk of high
or low birth weight. The study was based on the Danish vitamin D fortification
programme, which was a societal intervention with mandatory fortification of
margarine during 1961-1985 and voluntary fortification of low-fat milk between
1972 and 1976. The influence of prenatal vitamin D exposure on birth weight was
investigated among 51 883 Danish children, by comparing birth weight among
individuals born during 2 years before or after the initiation and termination of
vitamin D fortification programmes. In total, four sets of analyses were
performed. Information on birth weight was available in the Copenhagen School
Health Record Register for all school children in Copenhagen. The mean birth
weight was lower among the exposed than non-exposed children during all study
periods (milk initiation - 20.3 (95 % CI - 39.2, - 1.4) g; milk termination -
25.9 (95 % CI - 46.0, - 5.7) g; margarine termination - 45.7 (95 % CI - 66.6, -
24.8) g), except during the period around the initiation of margarine
fortification, where exposed children were heavier than non-exposed children
(margarine initiation 27.4 (95 % CI 10.8, 44.0) g). No differences in the odds of
high (>4000 g) or low ( < 2500 g) birth weight were observed between the children
exposed and non-exposed to vitamin D fortification prenatally. Prenatal exposure
to vitamin D from fortified margarine and milk altered birth weight, but the
effect was small and inconsistent, reaching the conclusion that vitamin D
fortification seems to be clinically irrelevant in relation to fetal growth.
PMID- 25140845
TI - Simeprevir for hepatitis C virus.
PMID- 25140846
TI - Essential tremor versus Parkinson disease: Make the right diagnosis.
PMID- 25140847
TI - Infective endocarditis: Beyond TEE.
PMID- 25140848
TI - Advocacy can overcome acts of derision.
PMID- 25140851
TI - Connecting with chronically ill patients to improve treatment adherence.
AB - This study presents an integrative review of the literature assessing the
relationships among a patient's style in coping with a long-term health
condition, the patient-practitioner therapeutic alliance, and treatment adherence
among chronically ill adults. Evidence-based recommendations to improve nurse
practitioner-patient therapeutic alliance and treatment adherence are suggested.
PMID- 25140852
TI - Preexposure prophylaxis: An emerging clinical approach to preventing HIV in high
risk adults.
AB - The HIV antiretroviral drug emtricitabine/tenofovir disoproxil fumarate (Truvada)
was recently approved as preexposure prophylaxis (PrEP) therapy for adults at
high risk for sexually acquired HIV infection. This article reviews the data
supporting the efficacy of PrEP, and provides other relevant data regarding the
implementation of PrEP.
PMID- 25140854
TI - Phytomonitoring of chlorinated ethenes in trees: a four-year study of seasonal
chemodynamics in planta.
AB - Long-term monitoring (LTM) of groundwater remedial projects is costly and time
consuming, particularly when using phytoremediation, a long-term remedial
approach. The use of trees as sensors of groundwater contamination (i.e.,
phytoscreening) has been widely described, although the use of trees to provide
long-term monitoring of such plumes (phytomonitoring) has been more limited due
to unexplained variability of contaminant concentrations in trees. To assess this
variability, we developed an in planta sampling method to obtain high-frequency
measurements of chlorinated ethenes in oak (Quercus rubra) and baldcypress
(Taxodium distichum) trees growing above a contaminated plume during a 4-year
trial. The data set revealed that contaminant concentrations increased rapidly
with transpiration in the spring and decreased in the fall, resulting in
perchloroethene (PCE) and trichloroethene (TCE) sapwood concentrations an order
of magnitude higher in late summer as compared to winter. Heartwood PCE and TCE
concentrations were more buffered against seasonal effects. Rainfall events
caused negligible dilution of contaminant concentrations in trees after
precipitation events. Modeling evapotranspiration potential from meteorological
data and comparing the modeled uptake and transport with the 4 years of high
frequency data provides a foundation to advance the implementation of
phytomonitoring and improved understanding of plant contaminant interactions.
PMID- 25140856
TI - Ebola virus disease in West Africa--no early end to the outbreak.
PMID- 25140855
TI - The international Ebola emergency.
PMID- 25140857
TI - Studying "secret serums"--toward safe, effective Ebola treatments.
PMID- 25140858
TI - Ebola 2014--new challenges, new global response and responsibility.
PMID- 25140859
TI - Women more vulnerable than men when facing risk for treatment-induced
infertility: a qualitative study of young adults newly diagnosed with cancer.
AB - BACKGROUND: Being diagnosed with cancer constitutes not only an immediate threat
to health, but cancer treatments may also have a negative impact on fertility.
Retrospective studies show that many survivors regret not having received
fertility-related information and being offered fertility preservation at time of
diagnosis. This qualitative study investigates newly diagnosed cancer patients'
experiences of fertility-related communication and how they reason about the risk
of future infertility. MATERIAL AND METHODS: Informants were recruited at three
cancer wards at a university hospital. Eleven women and 10 men newly diagnosed
with cancer participated in individual semi-structured interviews focusing on
three domains: experiences of fertility-related communication, decision-making
concerning fertility preservation, and thoughts and feelings about the risk of
possible infertility. Data was analyzed through qualitative content analysis.
RESULTS: The analysis resulted in three sub-themes, 'Getting to know', 'Reacting
to the risk' and 'Handling uncertainty', and one main theme 'Women more
vulnerable when facing risk for infertility', indicating that women reported more
negative experiences related to patient-provider communication regarding
fertility-related aspects of cancer treatment, as well as negative emotional
reactions to the risk of infertility and challenges related to handling
uncertainty regarding future fertility. The informants described distress when
receiving treatment with possible impact on fertility and used different
strategies to handle the risk for infertility, such as relying on fertility
preservation or thinking of alternative ways to achieve parenthood. The negative
experiences reported by the female informants may be related to the fact that
none of the women, but almost all men, had received information about and used
fertility preservation. CONCLUSIONS: Women newly diagnosed with cancer seem to be
especially vulnerable when facing risk for treatment-induced infertility. Lack of
shared decision-making concerning future fertility may cause distress and it is
therefore necessary to improve the fertility-related communication targeted to
female cancer patients.
PMID- 25140860
TI - Outcomes of stereotactic radiotherapy for cranial and extracranial metastatic
renal cell carcinoma: a systematic review.
AB - BACKGROUND: Stereotactic radiotherapy is a non-invasive, ablative technique which
may be particularly effective in treating metastatic renal cell carcinoma (RCC).
The study objective was to analyse outcomes and toxicity of stereotactic
radiotherapy in metastatic RCC. MATERIAL AND METHODS: Following the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a
systematic review of Medline was performed in March 2013. Exclusion criteria
included mixed histology studies and case series. Local control, overall survival
and toxicities were analysed. RESULTS: From 148 publications identified, 16 and
10 publications for cranial and extracranial metastatic RCC met inclusion
criteria, respectively. There were 810 intracranial patients and 2433 targets.
The weighted local control was 92%. Overall survival ranged from 6.7 to 25.6
months. Significant Grade 3-4 toxicity ranged from 0% to 6%. The weighted rate of
treatment-related mortality was 0.6%, all secondary to intratumoral haemorrhage.
There were 389 extracranial patients and 730 targets. The weighted local control
was 89%. Median overall survival ranged from 11.7 to 22 months. Grade 3-4
toxicity ranged from 0% to 4%. Treatment-related mortality was 0.5%. CONCLUSION:
Stereotactic radiotherapy is associated with excellent local control and low
rates of toxicity for intracranial and extracranial metastatic RCC. Future
randomised studies are required to confirm the additional benefit of Stereotactic
Ablative Body Radiotherapy (SABR) above standard conservative or palliative
approaches.
PMID- 25140861
TI - Nordic guidelines 2014 for diagnosis and treatment of gastroenteropancreatic
neuroendocrine neoplasms.
AB - BACKGROUND: The diagnostic work-up and treatment of patients with neuroendocrine
neoplasms (NENs) has undergone major recent advances and new methods are
currently introduced into the clinic. An update of the WHO classification has
resulted in a new nomenclature dividing NENs into neuroendocrine tumours (NETs)
including G1 (Ki67 index <= 2%) and G2 (Ki67 index 3-20%) tumours and
neuroendocrine carcinomas (NECs) with Ki67 index > 20%, G3. Aim. These Nordic
guidelines summarise the Nordic Neuroendocrine Tumour Group's current view on how
to diagnose and treat NEN-patients and are meant to be useful in the daily
practice for clinicians handling these patients.
PMID- 25140862
TI - Fatigue in male lymphoma survivors differs between diagnostic groups and is
associated with latent hypothyroidism.
AB - BACKGROUND: Few studies have explored fatigue in different groups of lymphoma
survivors and the association with hormonal dysfunctions. The aims were to
analyze associations between fatigue and thyroid and gonadal function in male
lymphoma survivors. In addition, the impact of chronic fatigue on work situation
and daily functioning were explored. PATIENTS AND METHODS: This cross-sectional
study included male lymphoma survivors diagnosed in 1980-2002, aged <= 50 years
at diagnosis and > 18 years at survey in 2007. The participants (n = 233, median
age at survey: 48 years, median observation time: 15 years) completed
questionnaires assessing levels of fatigue, chronic fatigue (duration >= 6
months), mental distress, daily functioning and work situation. Levels of thyroid
and gonadal hormones were assessed. The participants were grouped according to
diagnosis: Hodgkin lymphoma (HL, n = 131), aggressive/very aggressive non-Hodgkin
lymphoma (NHL) (n = 67) and indolent NHL (n = 35). Thyroid hormones were
categorized as normal (n = 174) or latent hypothyroidism (elevated thyroid
stimulating hormone, n = 59). Gonadal hormones were categorized as normal (n =
111), elevated follicle stimulating hormone only (n = 45), primary (n = 35) or
secondary hypogonadism (n = 42). Uni- and multivariate regression analyses were
performed. A p value < 0.05 indicated the level of significance. RESULTS: The
survivors of HL and aggressive/very aggressive NHL had similar fatigue levels and
similar prevalence of chronic fatigue (HL: 31%, aggressive/very aggressive; NHL:
27%). Survivors of indolent NHL had lower fatigue levels and prevalence of
chronic fatigue (11%). Latent hypothyroidism was associated with increased
fatigue levels (p = 0.042). Gonadal function was not associated with levels of
fatigue or chronic fatigue. Mental distress was associated with increasing
fatigue levels and chronic fatigue (p < 0.001). We found negative associations
between chronic fatigue, daily functioning and work status. CONCLUSIONS: Fatigued
lymphoma survivors should be investigated for thyroid function. The negative
impact of chronic fatigue on daily functioning and work status emphasizes the
importance of maintaining the effort in understanding the mechanisms behind
fatigue.
PMID- 25140863
TI - Comparison of bilateral and unilateral contractions between swimmers and
nonathletes during leg press and hand grip exercises.
AB - The bilateral limb deficit (BLD) is defined as the reduction in force production
during bilateral compared with summed unilateral contractions of homologous
muscles. The underlying mechanism for the BLD has been elusive to determine. The
purpose of this study was to examine the presence of the BLD during maximal
isometric leg press and handgrip exercises in female swimmers (n = 9, mean age =
20.1 +/- 1.3 years) and nonathletes (n = 9, mean age = 21.7 +/- 1.3 years) to
gain further insight into this phenomenon. Force and electromyography (EMG)
measures were collected from participants under bilateral and unilateral
conditions for handgrip and leg press exercises. Bilateral limb ratios (BLR) were
calculated for swimmers (BLRS) and nonathletes (BLRNA). A deficit was found for
swimmers and nonathletes in leg force (BLRS = 79.84% +/- 13.09% and BLRNA =
81.44% +/- 19.23%) and leg EMG (BLRS = 88.45% +/- 15.41% and BLRNA = 94.66% +/-
13.62%); however, no BLD was seen in hand force (BLRS = 98.30% +/- 11.21% and
BLRNA = 95.91% +/- 11.04%) and hand EMG (BLRS = 102.42% +/- 11.20% and BLRNA =
103.30% +/- 16.50%). Furthermore, no significant differences were found between
groups for leg force, leg EMG, hand force, and hand EMG. In conclusion, a BLD was
detected for both groups during bilateral isometric leg press. This suggests that
while the BLD may be affected by neural influences, there may other factors
involved such as postural stability requirements to perform the exercise.
PMID- 25140864
TI - TGFbeta: A player on multiple fronts in the tumor microenvironment.
AB - The physiological functions of transforming growth factor (TGF)-beta in cell
signaling include regulation of developmental processes and cell growth. Tumor
cells very often display altered regulation of the TGFbeta signaling pathway,
either by defects in TGFbeta itself or in downstream components of the pathway.
TGFbeta can play a dual role in tumorigenesis, i.e. it can be either tumor
suppressive or tumor-promoting. TGFbeta suppresses the growth of tumor cells;
however, in advanced tumors, it is associated with induction of progression,
resulting in poor prognosis for patients. The TGFbeta negative regulation of
cytotoxic cell function, together with the promotion of T-regulatory cell
maturation, impairs anti-tumor responses. Recent studies have elucidated new
roles for TGFbeta signaling in the tumor microenvironment. Abrogation of proper
signaling induces epithelial-to-mesenchymal transition with pro-metastatic
functions, resulting in cancer progression. Thus, TGFbeta signaling in the tumor
microenvironment plays an important role in tumor initiation, progression, and
metastasis by its capacity to regulate cross-talk between tumor cells and other
components of the local environment.
PMID- 25140865
TI - Ligand structures of synthetic deoxa-pyranosylamines with raucaffricine and
strictosidine glucosidases provide structural insights into their binding and
inhibitory behaviours.
AB - Insight into the structure and inhibition mechanism of O-beta-d-glucosidases by
deoxa-pyranosylamine type inhibitors is provided by X-ray analysis of complexes
between raucaffricine and strictosidine glucosidases and N-(cyclohexylmethyl)-, N
(cyclohexyl)- and N-(bromobenzyl)-beta-d-gluco-1,5-deoxa-pyranosylamine. All
inhibitors anchored exclusively in the catalytic active site by competition with
appropriate enzyme substrates. Thus facilitated prospective elucidation of the
binding networks with residues located at <3.9 A distance will enable the
development of potent inhibitors suitable for the production of valuable alkaloid
glucosides, raucaffricine and strictosidine, by means of synthesis in Rauvolfia
serpentina cell suspension cultures.
PMID- 25140866
TI - Impact of acute guanfacine administration on stress and cue reactivity in cocaine
dependent individuals.
AB - BACKGROUND: Stress and drug-paired cues increase drug craving and noradrenergic
activity in cocaine-dependent individuals. Thus, medications that attenuate
noradrenergic activity may be effective therapeutic treatment options for cocaine
dependent individuals. OBJECTIVES: To examine the impact of acute administration
of the alpha2 adrenergic receptor agonist guanfacine on responses to multiple
risk factors for relapse in cocaine-dependent individuals. METHODS: In a double
blind, placebo-controlled study, cocaine-dependent individuals (n = 84), were
randomized to receive either 2 mg guanfacine (n = 50) or placebo (n = 34). Within
each treatment arm, subjects were randomized to either a stress (guanfacine n =
26; placebo n = 15) or a no-stress (guanfacine n = 24; placebo n = 19) group.
Participants in the stress group performed the Trier Social Stress Test. Subjects
in each group were exposed to a neutral cue and then to cocaine-related cues.
Plasma cortisol and subjective responses were compared between the four groups.
RESULTS: The no-stress guanfacine group reported greater craving in response to
cocaine cues as compared to the neutral cue (p < 0.001). The guanfacine stress
group reported greater subjective stress at the neutral cue than at baseline (p =
0.032). The cocaine cue increased subjective stress in the guanfacine (p < 0.001)
no-stress group. There were no effects of guanfacine on cortisol levels in either
the stress or no stress groups (all p > 0.70). CONCLUSION: This study found no
effects of a single 2 mg dose of guanfacine on reactivity to stress and cues
alone or on the interaction of stress and drug cues. In cocaine-dependent
individuals an acute 2 mg dose of guanfacine may not be an effective therapeutic
treatment strategy.
PMID- 25140867
TI - The potential role of anticoagulant therapy for the secondary prevention of
ischemic events post-acute coronary syndrome.
AB - Abstract The use of dual antiplatelet therapy has led to a substantial reduction
in ischemic events post-acute coronary syndrome (ACS). Despite this, recurrent
event rates remain high. Recent research has combined antiplatelet with
anticoagulant therapy to reduce recurrent event rates further. Compared with
standard medical therapy, rivaroxaban demonstrated improved efficacy outcomes and
significantly reduced mortality after an ACS. Although clear benefits of novel
oral anticoagulants post-ACS have been proven, concerns regarding bleeding are
still a barrier to widespread use. This review explores key trials of dual
antiplatelet therapy and examines the latest research in anticoagulation aiming
to optimize clinical outcomes post-ACS.
PMID- 25140868
TI - Non-occupational post-exposure prophylaxis for HIV: 10-year retrospective
analysis in Seattle, Washington.
AB - Despite treatment guidelines in place since 2005, non-occupational post-exposure
HIV prophylaxis (nPEP) remains an underutilized prevention strategy. We conducted
a retrospective chart review of patients presenting to a publicly-funded HIV
clinic in Seattle, Washington for nPEP between 2000 and 2010 (N = 360). nPEP
prescriptions were provided for 324 (90%) patients; 83% of prescription decisions
were appropriate according to Centers for Disease Control and Prevention
guidelines, but only 31% (N = 111/360) of patients were considered "high risk."
In order to use limited resources most efficiently, public health agencies should
target messaging for this high-cost intervention to individuals with high-risk
HIV exposures.
PMID- 25140869
TI - Dental auxiliaries for dental care traditionally provided by dentists.
AB - BACKGROUND: Poor or inequitable access to oral health care is commonly reported
in high-, middle- and low-income countries. Although the severity of these
problems varies, a lack of supply of dentists and their uneven distribution are
important factors. Delegating care to dental auxiliaries could ease this problem,
extend services to where they are unavailable and liberate time for dentists to
do more complex work. Before such an approach can be advocated, it is important
to know the relative effectiveness of dental auxiliaries and dentists.
OBJECTIVES: To assess the effectiveness, costs and cost effectiveness of dental
auxiliaries in providing care traditionally provided by dentists. SEARCH METHODS:
We searched the following electronic databases from their inception dates up to
November 2013: the Cochrane Effective Practice and Organisation of Care (EPOC)
Group's Specialised Register; Cochrane Oral Health Group's Specialised Register;
the Cochrane Central Register of Controlled Trials (Issue 11, 2013); MEDLINE;
EMBASE; CINAHL; Cochrane Database of Systematic Reviews; Database of Abstracts of
Reviews of Effectiveness; five other databases and two trial registries. We also
undertook a grey literature search and searched the reference list of included
studies and contacted authors of relevant papers. SELECTION CRITERIA: We included
randomised controlled trials (RCTs), non-randomised controlled clinical trials
(NRCTs), interrupted time series (ITSs) and controlled before and after studies
(CBAs) evaluating the effectiveness of dental auxiliaries compared with dentists
in undertaking clinical tasks traditionally performed by a dentist. DATA
COLLECTION AND ANALYSIS: Three review authors independently applied eligibility
criteria, extracted data and assessed the risk of bias of each included study and
two review authors assessed the quality of the evidence from the included
studies, according to The Cochrane Collaboration's procedures. Since meta
analysis was not possible, we gave a narrative description of the results. MAIN
RESULTS: We identified five studies (one cluster RCT, three RCTs and one NRCT),
evaluating the effectiveness of dental auxiliaries compared with dentists in
providing dental care traditionally provided by dentists, eligible for inclusion
in this review. The included studies, which involved 13 dental auxiliaries, six
dentists, and more than 1156 participants, evaluated two clinical
tasks/techniques: placement of preventive resin fissure sealants and the
atraumatic restorative technique (ART). Two studies were conducted in the US, and
one each in Canada, Gambia and Singapore.Of the four studies evaluating
effectiveness in placing preventive resin fissure sealants, three found no
evidence of a difference in retention rates of those placed by dental auxiliaries
and dentists over a range of follow-up periods (six to 24 months). One study
found that fissure sealants placed by a dental auxiliary had lower retention
rates than one placed by a dentist after 48 months (9.0% with auxiliary versus
29.1% with dentist). The same study reported that the net reduction after 48
months in the number teeth exhibiting caries (dental decay) was lower for teeth
treated by the dental auxiliary than the dentist (3 with auxiliary versus 60 with
dentist, P value < 0.001).One study showed no evidence of a difference in dental
decay after treatment with fissure sealants between groups. The one study
comparing the effectiveness of dental auxiliaries and dentists in performing ART
reported no difference in survival rates of the restorations (fillings) after 12
months.All studies were at high risk of bias and the overall quality of the
evidence was very low, as assessed using the GRADE approach. In addition, four of
the included studies were more than 20 years old; the materials used and the
techniques assessed were out of date. We found no eligible studies comparing the
effectiveness of dental auxiliaries and dentists in the diagnosis of oral
diseases and conditions, in delivering oral health education and other aspects of
health promotion, or studies assessing participants' perspectives including the
acceptability of care received. None of the included studies reported adverse
effects. In addition, we found no studies comparing the costs and cost
effectiveness of dental auxiliaries and dentists, their impact on access and
equity of access to care that met the pre-specified inclusion criteria. AUTHORS'
CONCLUSIONS: We only identified five studies for inclusion in this review, all of
which were at high risk of bias and four were published more than 20 years ago,
highlighting the paucity of high-quality evaluations of the relative
effectiveness, cost-effectiveness and safety of dental auxiliaries compared with
dentists in performing clinical tasks. No firm conclusions could be drawn from
the present review about the relative effectiveness of dental auxiliaries and
dentists.
PMID- 25140870
TI - Emotions under discussion: gender, status and communication in online
collaboration.
AB - BACKGROUND: Despite the undisputed role of emotions in teamwork, not much is
known about the make-up of emotions in online collaboration. Publicly available
repositories of collaboration data, such as Wikipedia editor discussions, now
enable the large-scale study of affect and dialogue in peer production. METHODS:
We investigate the established Wikipedia community and focus on how emotion and
dialogue differ depending on the status, gender, and the communication network of
the [Formula: see text] editors who have written at least 100 comments on the
English Wikipedia's article talk pages. Emotions are quantified using a word
based approach comparing the results of two predefined lexicon-based methods:
LIWC and SentiStrength. PRINCIPAL FINDINGS: We find that administrators maintain
a rather neutral, impersonal tone, while regular editors are more emotional and
relationship-oriented, that is, they use language to form and maintain
connections to other editors. A persistent gender difference is that female
contributors communicate in a manner that promotes social affiliation and
emotional connection more than male editors, irrespective of their status in the
community. Female regular editors are the most relationship-oriented, whereas
male administrators are the least relationship-focused. Finally, emotional and
linguistic homophily is prevalent: editors tend to interact with other editors
having similar emotional styles (e.g., editors expressing more anger connect more
with one another). CONCLUSIONS/SIGNIFICANCE: Emotional expression and linguistic
style in online collaboration differ substantially depending on the contributors'
gender and status, and on the communication network. This should be taken into
account when analyzing collaborative success, and may prove insightful to
communities facing gender gap and stagnation in contributor acquisition and
participation levels.
PMID- 25140871
TI - Synthetic antibodies with a human framework that protect mice from lethal Sudan
ebolavirus challenge.
AB - The ebolaviruses cause severe and rapidly progressing hemorrhagic fever. There
are five ebolavirus species; although much is known about Zaire ebolavirus (EBOV)
and its neutralization by antibodies, little is known about Sudan ebolavirus
(SUDV), which is emerging with increasing frequency. Here we describe monoclonal
antibodies containing a human framework that potently inhibit infection by SUDV
and protect mice from lethal challenge. The murine antibody 16F6, which binds the
SUDV envelope glycoprotein (GP), served as the starting point for design.
Sequence and structural alignment revealed similarities between 16F6 and YADS1, a
synthetic antibody with a humanized scaffold. A focused phage library was
constructed and screened to impart 16F6-like recognition properties onto the
YADS1 scaffold. A panel of 17 antibodies were characterized and found to have a
range of neutralization potentials against a pseudotype virus infection model.
Neutralization correlated with GP binding as determined by ELISA. Two of these
clones, E10 and F4, potently inhibited authentic SUDV and conferred protection
and memory immunity in mice from lethal SUDV challenge. E10 and F4 were further
shown to bind to the same epitope on GP as 16F6 with comparable affinities. These
antibodies represent strong immunotherapeutic candidates for treatment of SUDV
infection.
PMID- 25140873
TI - The first ant-termite syninclusion in amber with CT-scan analysis of taphonomy.
AB - We describe here a co-occurrence (i.e. a syninclusion) of ants and termites in a
piece of Mexican amber (Totolapa deposit, Chiapas), whose importance is two-fold.
First, this finding suggests at least a middle Miocene antiquity for the modern,
though poorly documented, relationship between Azteca ants and Nasutitermes
termites. Second, the presence of a Neivamyrmex army ant documents an in situ
raiding behaviour of the same age and within the same community, confirmed by the
fact that the army ant is holding one of the termite worker between its mandibles
and by the presence of a termite with bitten abdomen. In addition, we present how
CT-scan imaging can be an efficient tool to describe the topology of resin flows
within amber pieces, and to point out the different states of preservation of the
embedded insects. This can help achieving a better understanding of taphonomical
processes, and tests ethological and ecological hypotheses in such complex
syninclusions.
PMID- 25140872
TI - Identity and specificity of Rhizoctonia-like fungi from different populations of
Liparis japonica (Orchidaceae) in Northeast China.
AB - Mycorrhizal association is known to be important to orchid species, and a
complete understanding of the fungi that form mycorrhizas is required for orchid
ecology and conservation. Liparis japonica (Orchidaceae) is a widespread
terrestrial photosynthetic orchid in Northeast China. Previously, we found the
genetic diversity of this species has been reduced recent years due to habitat
destruction and fragmentation, but little was known about the relationship
between this orchid species and the mycorrhizal fungi. The Rhizoctonia-like fungi
are the commonly accepted mycorrhizal fungi associated with orchids. In this
study, the distribution, diversity and specificity of culturable Rhizoctonia-like
fungi associated with L. japonica species were investigated from seven
populations in Northeast China. Among the 201 endophytic fungal isolates
obtained, 86 Rhizoctonia-like fungi were identified based on morphological
characters and molecular methods, and the ITS sequences and phylogenetic analysis
revealed that all these Rhizoctonia-like fungi fell in the same main clade and
were closely related to those of Tulasnella calospora species group. These
findings indicated the high mycorrhizal specificity existed in L. japonica
species regardless of habitats at least in Northeast China. Our results also
supported the wide distribution of this fungal partner, and implied that the
decline of L. japonica in Northeast China did not result from high mycorrhizal
specificity. Using culture-dependent technology, these mycorrhizal fungal
isolates might be important sources for the further utilizing in orchids
conservation.
PMID- 25140874
TI - Functional connectivity in the first year of life in infants at risk for autism
spectrum disorder: an EEG study.
AB - In the field of autism research, recent work has been devoted to studying both
behavioral and neural markers that may aide in early identification of autism
spectrum disorder (ASD). These studies have often tested infants who have a
significant family history of autism spectrum disorder, given the increased
prevalence observed among such infants. In the present study we tested infants at
high- and low-risk for ASD (based on having an older sibling diagnosed with the
disorder or not) at 6- and 12-months-of-age. We computed intrahemispheric linear
coherence between anterior and posterior sites as a measure of neural functional
connectivity derived from electroencephalography while the infants were listening
to speech sounds. We found that by 12-months-of-age infants at risk for ASD
showed reduced functional connectivity compared to low risk infants. Moreover, by
12-months-of-age infants later diagnosed with ASD showed reduced functional
connectivity, compared to both infants at low risk for the disorder and infants
at high risk who were not later diagnosed with ASD. Significant differences in
functional connectivity were also found between low-risk infants and high-risk
infants who did not go onto develop ASD. These results demonstrate that reduced
functional connectivity appears to be related to genetic vulnerability for ASD.
Moreover, they provide further evidence that ASD is broadly characterized by
differences in neural integration that emerge during the first year of life.
PMID- 25140875
TI - A biological micro actuator: graded and closed-loop control of insect leg motion
by electrical stimulation of muscles.
AB - In this study, a biological microactuator was demonstrated by closed-loop motion
control of the front leg of an insect (Mecynorrhina torquata, beetle) via
electrical stimulation of the leg muscles. The three antagonistic pairs of muscle
groups in the front leg enabled the actuator to have three degrees of freedom:
protraction/retraction, levation/depression, and extension/flexion. We observed
that the threshold amplitude (voltage) required to elicit leg motions was
approximately 1.0 V; thus, we fixed the stimulation amplitude at 1.5 V to ensure
a muscle response. The leg motions were finely graded by alternation of the
stimulation frequencies: higher stimulation frequencies elicited larger leg
angular displacement. A closed-loop control system was then developed, where the
stimulation frequency was the manipulated variable for leg-muscle stimulation
(output from the final control element to the leg muscle) and the angular
displacement of the leg motion was the system response. This closed-loop control
system, with an optimized proportional gain and update time, regulated the leg to
set at predetermined angular positions. The average electrical stimulation power
consumption per muscle group was 148 uW. These findings related to and
demonstrations of the leg motion control offer promise for the future development
of a reliable, low-power, biological legged machine (i.e., an insect-machine
hybrid legged robot).
PMID- 25140876
TI - The effects of fluctuations in the nutrient supply on the expression of five
members of the AGL17 clade of MADS-box genes in rice.
AB - The ANR1 MADS-box gene in Arabidopsis is a key gene involved in regulating
lateral root development in response to the external nitrate supply. There are
five ANR1-like genes in Oryza sativa, OsMADS23, OsMADS25, OsMADS27, OsMADS57 and
OsMADS61, all of which belong to the AGL17 clade. Here we have investigated the
responsiveness of these genes to fluctuations in nitrogen (N), phosphorus (P) and
sulfur (S) mineral nutrient supply. The MADS-box genes have been shown to have a
range of responses to the nutrient supply. The expression of OsMADS61 was
transiently induced by N deprivation but was not affected by re-supply with
various N sources. The expression of OsMADS25 and OsMADS27 was induced by re
supplying with NO3(-) and NH4NO3, but downregulated by NH4(+). The expression of
OsMADS57 was significantly downregulated by N starvation and upregulated by 3 h
NO3(-) re-supply. OsMADS23 was the only gene that showed no response to either N
starvation nor NO3(-) re-supply. OsMADS57 was the only gene not regulated by P
fluctuation whereas the expression of OsMADS23, OsMADS25 and OsMADS27 was
downregulated by P starvation and P re-supply. In contrast, all five ANR1-related
genes were significantly upregulated by S starvation. Our results also indicated
that there were interactions among nitrate, sulphate and phosphate transporters
in rice.
PMID- 25140877
TI - Enhancing TB case detection: experience in offering upfront Xpert MTB/RIF testing
to pediatric presumptive TB and DR TB cases for early rapid diagnosis of drug
sensitive and drug resistant TB.
AB - BACKGROUND: Diagnosis of pulmonary tuberculosis (PTB) in children is challenging
due to difficulties in obtaining good quality sputum specimens as well as the
paucibacillary nature of disease. Globally a large proportion of pediatric
tuberculosis (TB) cases are diagnosed based only on clinical findings. Xpert
MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution
in addressing these challenges. This study presents the results from pediatric
groups taking part in a large demonstration study wherein Xpert MTB/RIF testing
replaced smear microscopy for all presumptive PTB cases in public health
facilities across India. METHODS: The study covered a population of 8.8 million
across 18 programmatic sub-district level tuberculosis units (TU), with one Xpert
MTB/RIF platform established at each study TU. Pediatric presumptive PTB cases
(both TB and Drug Resistant TB (DR-TB)) accessing any public health facilities in
study area were prospectively enrolled and tested on Xpert MTB/RIF following a
standardized diagnostic algorithm. RESULTS: 4,600 pediatric presumptive pulmonary
TB cases were enrolled. 590 (12.8%, CI 11.8-13.8) pediatric PTB were diagnosed.
Overall 10.4% (CI 9.5-11.2) of presumptive PTB cases had positive results by
Xpert MTB/RIF, compared with 4.8% (CI 4.2-5.4) who had smear-positive results.
Upfront Xpert MTB/RIF testing of presumptive PTB and presumptive DR-TB cases
resulted in diagnosis of 79 and 12 rifampicin resistance cases, respectively.
Positive predictive value (PPV) for rifampicin resistance detection was high
(98%, CI 90.1-99.9), with no statistically significant variation with respect to
past history of treatment. CONCLUSION: Upfront access to Xpert MTB/RIF testing in
pediatric presumptive PTB cases was associated with a two-fold increase in
bacteriologically-confirmed PTB, and increased detection of rifampicin-resistant
TB cases under routine operational conditions across India. These results suggest
that routine Xpert MTB/RIF testing is a promising solution to present-day
challenges in the diagnosis of PTB in pediatric patients.
PMID- 25140878
TI - Elevated heart rate triggers action potential alternans and sudden death.
translational study of a homozygous KCNH2 mutation.
AB - BACKGROUND: Long QT syndrome (LQTS) leads to arrhythmic events and increased risk
for sudden cardiac death (SCD). Homozygous KCNH2 mutations underlying LQTS-2 have
previously been termed "human HERG knockout" and typically express severe
phenotypes. We studied genotype-phenotype correlations of an LQTS type 2 mutation
identified in the homozygous index patient from a consanguineous Turkish family
after his brother died suddenly during febrile illness. METHODS AND RESULTS:
Clinical work-up, DNA sequencing, mutagenesis, cell culture, patch-clamp, in
silico mathematical modelling, protein biochemistry, confocal microscopy were
performed. Genetic analysis revealed a homozygous C-terminal KCNH2 mutation
(p.R835Q) in the index patient (QTc ~506 ms with notched T waves). Parents were I
degrees cousins - both heterozygous for the mutation and clinically unremarkable
(QTc ~447 ms, father and ~396 ms, mother). Heterologous expression of KCNH2-R835Q
showed mildly reduced current amplitudes. Biophysical properties of ionic
currents were also only nominally changed with slight acceleration of
deactivation and more negative V50 in R835Q-currents. Protein biochemistry and
confocal microscopy revealed similar expression patterns and trafficking of WT
and R835Q, even at elevated temperature. In silico analysis demonstrated mildly
prolonged ventricular action potential duration (APD) compared to WT at a cycle
length of 1000 ms. At a cycle length of 350 ms M-cell APD remained stable in WT,
but displayed APD alternans in R835Q. CONCLUSION: Kv11.1 channels affected by the
C-terminal R835Q mutation display mildly modified biophysical properties, but
leads to M-cell APD alternans with elevated heart rate and could precipitate SCD
under specific clinical circumstances associated with high heart rates.
PMID- 25140880
TI - A microfluidic linear node array for the study of protein-ligand interactions.
AB - We have developed a microfluidic device for the continuous separation of small
molecules from a protein mixture and demonstrated its practical use in the study
of protein-ligand binding, a crucial aspect in drug discovery. Our results
demonstrated dose-dependent binding between bovine serum albumin (BSA) and its
small-molecule site marker, Eosin Y (EY), and found that the binding reached a
plateau when the BSA : EY ratio was above 1, which agreed with the eosin binding
capacity of BSA reported in literature. By streamline control using a combination
of two fundamental building blocks (R and L nodes) with a microdevice operated at
a high flow rate (up to 1300 MUL h(-1)), a solution barrier was created to
"filter" off protein/protein-ligand complexes such that the small unbound
molecules were isolated and quantified easily. The percentage decrease of small
molecules with increasing protein concentration indicated the presence of binding
events. Several fluorophores with different molecular weights were used to test
the performance of the microfluidic "filter", which was tunable by 1) the total
flow rate, and/or 2) the flow distribution ratio between the two device inlets;
both were easily controllable by changing the syringe pump settings. Since the
microdevice was operated at a relatively high flow rate, aliquots were easily
recovered from the device outlets to facilitate off-chip detection. This
microfluidic design is a novel and promising tool for preliminary drug screening.
PMID- 25140881
TI - Unprecedented catalytic activity of Fe(NO3)3.9H2O: regioselective synthesis of 2
nitroimidazopyridines via oxidative amination.
AB - A unique iron-catalyzed oxidative diamination of nitroalkene with 2-aminopyridine
for the synthesis of 2-nitro-3-arylimidazo[1,2-a]pyridines with complete
regioselectivity has been achieved under mild and aerobic reaction conditions.
This is the first method for the synthesis of 2-nitroimidazo[1,2-a]pyridines.
These scaffolds were also synthesized directly from styrenes.
PMID- 25140882
TI - Biogeographic distribution patterns and their correlates in the diverse frog
fauna of the Atlantic Forest hotspot.
AB - Anurans are a highly diverse group in the Atlantic Forest hotspot (AF), yet
distribution patterns and species richness gradients are not randomly distributed
throughout the biome. Thus, we explore how anuran species are distributed in this
complex and biodiverse hotspot, and hypothesize that this group can be
distinguished by different cohesive regions. We used range maps of 497 species to
obtain a presence/absence data grid, resolved to 50*50 km grain size, which was
submitted to k-means clustering with v-fold cross-validation to determine the
biogeographic regions. We also explored the extent to which current environmental
variables, topography, and floristic structure of the AF are expected to identify
the cluster patterns recognized by the k-means clustering. The biogeographic
patterns found for amphibians are broadly congruent with ecoregions identified in
the AF, but their edges, and sometimes the whole extent of some clusters, present
much less resolved pattern compared to previous classification. We also
identified that climate, topography, and vegetation structure of the AF explained
a high percentage of variance of the cluster patterns identified, but the
magnitude of the regression coefficients shifted regarding their importance in
explaining the variance for each cluster. Specifically, we propose that the
anuran fauna of the AF can be split into four biogeographic regions: a) less
diverse and widely-ranged species that predominantly occur in the inland
semideciduous forests; b) northern small-ranged species that presumably evolved
within the Pleistocene forest refugia; c) highly diverse and small-ranged species
from the southeastern Brazilian mountain chain and its adjacent semideciduous
forest; and d) southern species from the Araucaria forest. Finally, the high
congruence among the cluster patterns and previous eco-regions identified for the
AF suggests that preserving the underlying habitat structure helps to preserve
the historical and ecological signals that underlie the geographic distribution
of AF anurans.
PMID- 25140883
TI - Histogram flow mapping with optical coherence tomography for in vivo skin
angiography of hereditary hemorrhagic telangiectasia.
AB - Speckle statistics of flowing scatterers have been well documented in the
literature. Speckle variance optical coherence tomography exploits the large
variance values of intensity changes in time caused mainly by the random
backscattering of light resulting from translational activity of red blood cells
to map out the microvascular networks. A method to map out the microvasculature
malformation of skin based on the time-domain histograms of individual pixels is
presented with results obtained from both normal skin and skin containing
vascular malformation. Results demonstrated that this method can potentially map
out deeper blood vessels and enhance the visualization of microvasculature in low
signal regions, while being resistant against motion (e.g., patient tremor or
internal reflex movements). The overall results are manifested as more uniform en
face projection maps of microvessels. Potential applications include clinical
imaging of skin vascular abnormalities and wide-field skin angiography for the
study of complex vascular networks.
PMID- 25140884
TI - Multiphoton fluorescence lifetime imaging microscopy reveals free-to-bound NADH
ratio changes associated with metabolic inhibition.
AB - Measurement of endogenous free and bound NAD(P)H relative concentrations in
living cells isa useful method for monitoring aspects of cellular metabolism,
because the NADH/NAD+ reduction-oxidation pair is crucial for electron transfer
through the mitochondrial electron transport chain. Variations of free and bound
NAD(P)H ratio are also implicated in cellular bioenergetic and biosynthetic
metabolic changes accompanying cancer. This study uses two-photon fluorescence
lifetime imaging microscopy (FLIM) to investigate metabolic changes in MCF10A
premalignant breast cancer cells treated with a range of glycolysis inhibitors:
namely, 2 deoxy-D-glucose, oxythiamine, lonidamine, and 4-(chloromethyl) benzoyl
chloride, as well as the mitochondrial membrane uncoupling agent carbonyl cyanide
m-chlorophenylhydrazone. Through systematic analysis of FLIM data from control
and treated cancer cells, we observed that all glycolytic inhibitors apart from
lonidamine had a slightly decreased metabolic rate and that the presence of serum
in the culture medium generally marginally protected cells from the effect of
inhibitors. Direct production of glycolytic L-lactate was also measured in both
treated and control cells. The combination of these two techniques gave valuable
insights into cell metabolism and indicated that FLIM was more sensitive than
traditional biochemical methods, as it directly measured metabolic changes within
cells as compared to quantification of lactate secreted by metabolically active
cells.
PMID- 25140885
TI - Identification of kidney tumor tissue by infrared spectroscopy of extracellular
matrix.
AB - Fourier transform infrared (FT-IR) spectroscopy was applied to characterize the
extracellular matrix (ECM) of kidney tumor tissue and normal kidney tissue.
Freshly resected tissue samples from 31 patients were pressed on a CaF2
substrate. FT-IR spectra obtained from ECM of tumor tissue exhibit stronger
absorption bands in the spectral region from 1000 to 1200 cm-1 and around 1750 cm
1 than those obtained from normal tissue. It is likely that the spectra of ECM of
kidney tumor tissue with large increases in the intensities of these bands
represent a higher concentration of fatty acids and glycerol. Amide I and amide
II bands are stronger in the spectra of ECM from normal tissue, indicating a
higher level of proteins. Our results suggest that FT-IR spectroscopy of the ECM
is an innovative emerging technology for real-time intraoperative tumor
diagnosis, which may improve margin clearance in renal cancer surgery.
PMID- 25140886
TI - Suzuki-Miyaura cross-coupling reactions of unprotected haloimidazoles.
AB - An efficient protocol for the palladium-catalyzed Suzuki-Miyaura cross-coupling
reaction of unprotected haloimidazoles is reported. The relatively mild reaction
conditions allow for ready access to a wide array of functionalized imidazole
derivatives in good to excellent yields. The synthetic utility of this method is
demonstrated by the total synthesis of nortopsentin D.
PMID- 25140887
TI - Unexpected metal ion-assisted transformations leading to unexplored bridging
ligands in Ni(II) coordination chemistry: the case of PO3F(2-) group.
AB - The initial 'accidental', metal ion-assisted hydrolysis of PF6(-) to PO3F(2-) has
been evolved in a systematic investigation of the bridging affinity of the latter
group in Ni(II)/oximate chemistry; mono-, di- and trinuclear complexes have been
prepared and confirmed both the rich reactivity of PO3F(2-) and its potential for
further use as bridging ligand in high-nuclearity 3d-metal cluster chemistry.
PMID- 25140888
TI - MicroRNAs as Mediators of the Ageing Process.
AB - Human ageing is a complex and integrated gradual deterioration of cellular
processes. There are nine major hallmarks of ageing, that include changes in DNA
repair and DNA damage response, telomere shortening, changes in control over the
expression and regulation of genes brought about by epigenetic and mRNA
processing changes, loss of protein homeostasis, altered nutrient signaling,
mitochondrial dysfunction, stem cell exhaustion, premature cellular senescence
and altered intracellular communication. Like practically all other cellular
processes, genes associated in features of ageing are regulated by miRNAs. In
this review, I will outline each of the features of ageing, together with
examples of specific miRNAs that have been demonstrated to be involved in each
one. This will demonstrate the interconnected nature of the regulation of
transcripts involved in human ageing, and the role of miRNAs in this process.
Definition of the factors involved in degeneration of organismal, tissue and
cellular homeostasis may provide biomarkers for healthy ageing and increase
understanding of the processes that underpin the ageing process itself.
PMID- 25140890
TI - Dynamic behavior of DNA cages anchored on spherically supported lipid bilayers.
AB - We report the anchoring of 3D-DNA-cholesterol labeled cages on spherically
supported lipid bilayer membranes (SSLBM) formed on silica beads, and their
addressability through strand displacement reactions, controlled membrane
orientation and templated dimerization. The bilayer-anchored cages can load three
different DNA-fluorophores by hybridization to their "top" face (furthest from
bilayer) and unload each of them selectively upon addition of a specific input
displacement strand. We introduce a method to control strand displacement from
their less accessible "bottom" face (closest to the bilayer), by adding
cholesterol-substituted displacing strands that insert into the bilayer
themselves in order to access the toehold region. The orientation of DNA cages
within the bilayer is tunable by positioning multiple cholesterol anchoring units
on the opposing two faces of the cage, thereby controlling their accessibility to
proteins and enzymes. A population of two distinct DNA cages anchored to the
SSLBMs exhibited significant membrane fluidity and have been directed into dimer
assemblies on bilayer via input of a complementary linking strand. Displacement
experiments performed on these anchored dimers indicate that removal of only one
prism's anchoring cholesterol strand was not sufficient to release the dimers
from the bilayer; however, removal of both cholesterol anchors from the dimerized
prisms via two displacement strands cleanly released the dimers from the bilayer.
This methodology allows for the anchoring of DNA cages on supported lipid
bilayers, the control of their orientation and accessibility within the bilayer,
and the programmable dimerization and selective removal of any of their
components. The facile coupling of DNA to other functional materials makes this
an attractive method for developing stimuli-responsive protein or nanoparticle
arrays, drug releasing biomedical device surfaces and self-healing materials for
light harvesting applications, using a highly modular, DNA-economic scaffold.
PMID- 25140891
TI - Partial hydrogenation of a tetranuclear titanium nitrido complex with ammonia
borane.
AB - The treatment of [{Ti(eta(5)-C5Me5)}4(MU3-N)4] with NH3BH3 leads to the
paramagnetic imidonitrido complex [{Ti(eta(5)-C5Me5)}4(MU3-N)3(MU3-NH)], which
can also be obtained by stepwise proton and electron transfer with HOTf and
[K(C5Me5)].
PMID- 25140889
TI - 4-1BBL enhances CD8+ T cell responses induced by vectored vaccines in mice but
fails to improve immunogenicity in rhesus macaques.
AB - T cells play a central role in the immune response to many of the world's major
infectious diseases. In this study we investigated the tumour necrosis factor
receptor superfamily costimulatory molecule, 4-1BBL (CD137L, TNFSF9), for its
ability to increase T cell immunogenicity induced by a variety of recombinant
vectored vaccines. To efficiently test this hypothesis, we assessed a number of
promoters and developed a stable bi-cistronic vector expressing both the antigen
and adjuvant. Co-expression of 4-1BBL, together with our model antigen TIP, was
shown to increase the frequency of murine antigen-specific IFN-gamma secreting
CD8(+) T cells in three vector platforms examined. Enhancement of the response
was not limited by co-expression with the antigen, as an increase in CD8(+)
immunogenicity was also observed by co-administration of two vectors each
expressing only the antigen or adjuvant. However, when this regimen was tested in
non-human primates using a clinical malaria vaccine candidate, no adjuvant effect
of 4-1BBL was observed limiting its potential use as a single adjuvant for
translation into a clinical vaccine.
PMID- 25140892
TI - Exonuclease III-assisted cascade signal amplification strategy for label-free and
ultrasensitive chemiluminescence detection of DNA.
AB - Detection of ultralow concentrations of specific nucleic acid sequences is a
central challenge in the early diagnosis of genetic diseases and biodefense
applications. Herein, we report a simple and homogeneous chemiluminescence (CL)
method for ultrasensitive DNA detection. It is based on the exonuclease III (Exo
III)-assisted cascade signal amplification and the catalytic effect of G
quadruplex-hemin DNAzyme on the luminol-H2O2 CL system. A quadruplex-forming DNA
probe hybridizes a hairpin DNA probe to construct a duplex DNA probe as
recognition element. Upon sensing of target DNA, the recognition of target DNA
and the duplex DNA probe triggers the Exo III cleavage process, accompanied by
releasing target DNA and generating a new secondary target DNA fragment. The
released target DNA and the secondary target DNA are recycled. Simultaneously,
numerous quadruplex-forming sequences are liberated and bind hemin to yield G
quadruplex-hemin DNAzyme, which subsequently catalyze the luminol-H2O2 reaction
to produce strong CL emission. This method exhibited a high sensitivity toward
target DNA with a detection limit of 8 fM, which was about 100 times lower than
that of the reported DNAzyme-based colorimetric system for DNA detection with Exo
III-assisted cascade signal amplification. This method provides a simple,
isothermal, and low-cost approach for sensitive detection of DNA and holds a
great potential for early diagnosis in gene-related diseases.
PMID- 25140893
TI - Uterine leiomyomas with bizarre nuclei: a clinicopathologic study of 59 cases.
AB - Leiomyoma with bizarre nuclei (LM-BN) is an uncommon tumor with histologic
features (mononucleated or multinucleated bizarre cells that may have a diffuse
distribution, prominent nucleoli, and karyorrhectic nuclei that may mimic
atypical mitoses) that often causes confusion with leiomyosarcoma. Fifty-nine LM
BNs were collected from our consultation files over the years 2000 to 2011.
Features recorded included patient age, therapy, tumor size, border, gross
appearance, density and distribution of BN, mitotic count, karyorrhectic nuclei,
prominent nucleoli, cells with conspicuous dense eosinophilic cytoplasm (rhabdoid
like), vascular changes and type of vasculature, and presence of necrosis and its
nature. Follow-up information was obtained for all patients. Patients ranged in
age from 25 to 75 (average 45) years (11 patients between 25 and 35 y, 20 between
36 and 45 y, 22 between 46 and 55 y, and 6 between 56 and 75 y). Forty-two
underwent hysterectomy and 17 myomectomy. For 51 tumors gross findings were
known. Forty (78%) had a solid white and whorled cut surface and 11 (22%) a
yellow appearance. Five (10%) neoplasms showed prominent cystic degeneration, and
hemorrhage and/or necrosis was seen in 9 (18%). Forty-five LM-BNs had a pushing
margin with the surrounding myometrium, whereas 1 showed irregular borders.
Margins could not be ascertained in the slides available in 13 cases. Twenty
eight (48%), 19 (32%), and 12 (20%) LM-BN showed low, intermediate, and high BN
density. Eighteen (30%) tumors showed diffuse, 26 (44%) showed multifocal, and 15
(26%) had focal BN distribution. Mitotic counts ranged from 0 to 7/10 high-power
fields (HPF) (average 1 to 2/10 HPF). Thirty-seven (63%) had <2/10 HPF, 19 (32%)
had 2 to 5 mitoses/10 HPF, and in 3 tumors (5%) mitotic counts were 6, 7, and
7/10 HPF (2 with focal and 1 with diffuse BN). All but 4 LM-BNs showed
karyorrhectic nuclei, striking in 12 neoplasms, mimicking atypical mitoses.
Nineteen (32%) LMs had prominent eosinophilic nucleoli surrounded by a clear
halo. Ischemic necrosis was detected in 21 (36%) LM-BN. Rhabdoid-like cells were
noted in 24 (41%) tumors. All patients had no evidence of recurrence, ranging
from 1 to 13 years (overall average 6 y; in patients with myomectomy 6.3 y with a
range of 2.6 to 11 y). Our results corroborate that LM-BN is associated with a
favorable outcome even in those patients only treated by myomectomy and
highlights that a conservative approach can be undertaken in these patients, as
many of them are of reproductive age. Because of the favorable outcome, the term
LM-BN is preferable to alternative terminology including "atypical leiomyoma."
PMID- 25140894
TI - Assessment of tumor regression of esophageal adenocarcinomas after neoadjuvant
chemotherapy: comparison of 2 commonly used scoring approaches.
AB - Histopathologic determination of tumor regression provides important prognostic
information for locally advanced gastroesophageal carcinomas after neoadjuvant
treatment. Regression grading systems mostly refer to the amount of therapy
induced fibrosis in relation to residual tumor or the estimated percentage of
residual tumor in relation to the former tumor site. Although these methods are
generally accepted, currently there is no common standard for reporting tumor
regression in gastroesophageal cancers. We compared the application of these 2
major principles for assessment of tumor regression: hematoxylin and eosin
stained slides from 89 resection specimens of esophageal adenocarcinomas
following neoadjuvant chemotherapy were independently reviewed by 3 pathologists
from different institutions. Tumor regression was determined by the 5-tiered
Mandard system (fibrosis/tumor relation) and the 4-tiered Becker system (residual
tumor in %). Interobserver agreement for the Becker system showed better weighted
kappa values compared with the Mandard system (0.78 vs. 0.62). Evaluation of the
whole embedded tumor site showed improved results (Becker: 0.83; Mandard: 0.73)
as compared with only 1 representative slide (Becker: 0.68; Mandard: 0.71).
Modification into simplified 3-tiered systems showed comparable interobserver
agreement but better prognostic stratification for both systems (log rank Becker:
P=0.015; Mandard P=0.03), with independent prognostic impact for overall survival
(modified Becker: P=0.011, hazard ratio=3.07; modified Mandard: P=0.023, hazard
ratio=2.72). In conclusion, both systems provide substantial to excellent
interobserver agreement for estimation of tumor regression after neoadjuvant
chemotherapy in esophageal adenocarcinomas. A simple 3-tiered system with the
estimation of residual tumor in % (complete regression/1% to 50% residual
tumor/>50% residual tumor) maintains the highest reproducibility and prognostic
value.
PMID- 25140895
TI - Metastatic renal cell carcinoma to the urinary bladder: a report of 11 cases.
AB - Metastatic renal cell carcinoma (RCC) to the urinary bladder is rarely seen.
Herein, we report the histologic subtypes, immunohistochemical characteristics,
and prognosis of 11 patients with metastatic RCC to the urinary bladder. The mean
age at the time of diagnosis of metastatic RCC to the bladder was 66 years
(range, 58 to 79 y). There were 9 male and 2 female patients. Four patients
presented with hematuria, 2 with urinary retention/obstruction, and 1 with
bladder calculi. Four patients were asymptomatic and presented for surveillance
cystoscopy, wherein they were found to have bladder masses. Nine patients had
prior histories of RCC. The remaining 2 patients presented with metastatic clear
cell RCC to the bladder and were subsequently found to have renal masses. The
average time between nephrectomy and metastasis to the bladder was 20.7 months
(range, 0 to 87 mo). Of the 10 patients with radical/partial nephrectomy, 7 cases
were clear cell (2 with sarcomatoid features), 2 papillary, and 1 chromophobe
with histologic fidelity between the primary and metastasis. Of cases with
available data, the primaries' ISUP nucleolar grades were 2 (n=2), 3 (n=4), and 4
for the 2 cases with sarcomatoid features. In 8 cases, the bladder RCC undermined
overlying urothelium with extensive urothelial denudation, and in 3 cases the RCC
was free floating without attachment to the urothelium. The 1 chromophobe RCC
metastasized with pagetoid spread to a preexisting urothelial papilloma. PAX8
immunohistochemistry was used to confirm the diagnosis in 2 cases. Three patients
have no evidence of disease (7, 9, and 13 mo). Two are alive with disease after
chemotherapy (30, 37 mo). Six patients are dead of disease with multiorgan
metastases; 4 are dead after therapy (5, 8, 25, 28 mo), and two died without
radiation or chemotherapy at 10 and 71 months. Metastatic RCC to the urinary
bladder is uncommon, with most cases clear cell RCC. In some cases, evidence
supports "drop metastases" as the mechanism of spread and patients have
relatively long survival. However, in other cases spread to the bladder is in the
setting of metastases to other sites, and these patients tended to die relatively
shortly after their bladder metastases.
PMID- 25140896
TI - Chemical vapor deposition of twisted bilayer and few-layer MoSe2 over SiO(x)
substrates.
AB - The chemical vapor deposition of monolayer and few-layer transition metal
dichalcogenides is a rapidly developing area of materials science due to the
exciting electrical, optical, thermal and mechanical properties of transition
metal dichalcogenides in their layered form. These properties make these
innovative materials potentially relevant to wide-ranging commercial
applications. One of these promising materials is MoSe2; however, just recently,
a few research groups have been able to demonstrate its synthesis via chemical
vapor deposition. Moreover, only oriented few-layer MoSe2 has been exhibited by
synthetically formed material using chemical vapor deposition thus far. Here, we
confirm twisted-layer MoSe2 can also form during chemical vapor deposition.
Twisted-layer transition metal dichalcogenides alter their properties as compared
to their oriented counterparts. Therefore, twisted-layer structures are of
interest because they can tune their properties.
PMID- 25140897
TI - Magnetically stabilized Fe8(MU4-S)6S8 clusters in Ba6Fe25S27.
AB - We have prepared Ba6Fe25S27, and studied its magnetic properties and electronic
structure. Single crystal diffraction revealed a cubic phase (Pm3[combining
macron]m) with a = 10.2057(9) A and Z = 1. Within the large cubic cell,
tetrahedrally coordinated Fe atoms arrange into octonuclear Fe8(MU4-S)6(S8)
clusters, which can be described as a cube of Fe atoms with six face-capping and
eight terminal S atoms. SQUID magnetometry measurements reveal an
antiferromagnetic transition at 25 K and anomalous high-temperature dependence of
magnetic susceptibility that is non-Curie like-two magnetic signatures which
mimic behavior seen in the parent phases of Fe-based superconductors. Using a
combined DFT and molecular orbital based approach, we provide an interpretation
of the bonding and stability within Ba6M25S27 (M = Fe, Co, Ni) and related M9S8
phases. Through a sigma-bonding molecular orbital model of the transition metal
coordination environments, we illustrate how the local stability can be enhanced
through addition of Ba. In addition, we perform spin-polarized DFT calculations
on Ba6Fe25S27 to determine the effect of adopting an antiferromagnetic spin state
on its electronic structure. By studying the magnetic properties from an
empirical and computational perspective, we hope to elucidate what aspects of the
magnetic structure are significant to bonding.
PMID- 25140898
TI - Diversity of biological effects induced by longwave UVA rays (UVA1) in
reconstructed skin.
AB - Despite their preponderance amongst the ultraviolet (UV) range received on Earth,
the biological impacts of longwave UVA1 rays (340-400 nm) upon human skin have
not been investigated so thoroughly. Nevertheless, recent studies have proven
their harmful effects and involvement in carcinogenesis and immunosuppression. In
this work, an in vitro reconstructed human skin model was used for exploring the
effects of UVA1 at molecular, cellular and tissue levels. A biological impact of
UVA1 throughout the whole reconstructed skin structure could be evidenced, from
morphology to gene expression analysis. UVA1 induced immediate injuries such as
generation of reactive oxygen species and thymine dimers DNA damage, accumulating
preferentially in dermal fibroblasts and basal keratinocytes, followed by
significant cellular alterations, such as fibroblast apoptosis and lipid
peroxidation. The full genome transcriptomic study showed a clear UVA1 molecular
signature with the modulation of expression of 461 and 480 genes in epidermal
keratinocytes and dermal fibroblasts, respectively (fold change> = 1.5 and
adjusted p value<0.001). Functional enrichment analysis using GO, KEGG pathways
and bibliographic analysis revealed a real stress with up-regulation of genes
encoding heat shock proteins or involved in oxidative stress response. UVA1 also
affected a wide panel of pathways and functions including cancer, proliferation,
apoptosis and development, extracellular matrix and metabolism of lipids and
glucose. Strikingly, one quarter of modulated genes was related to innate
immunity: genes involved in inflammation were strongly up-regulated while genes
involved in antiviral defense were severely down-regulated. These transcriptomic
data were confirmed in dose-response and time course experiments using
quantitative PCR and protein quantification. Links between the evidenced UVA1
induced impacts and clinical consequences of UVA1 exposure such as photo-aging,
photo-immunosuppression and cancer are discussed. These early molecular events
support the contribution of UVA1 to long term harmful consequences of UV exposure
and underline the need of an adequate UVA1 photoprotection.
PMID- 25140899
TI - Deciphering the glycolipid code of Alzheimer's and Parkinson's amyloid proteins
allowed the creation of a universal ganglioside-binding peptide.
AB - A broad range of microbial and amyloid proteins interact with cell surface
glycolipids which behave as infectivity and/or toxicity cofactors in human
pathologies. Here we have deciphered the biochemical code that determines the
glycolipid-binding specificity of two major amyloid proteins, Alzheimer's beta
amyloid peptide (Abeta) and Parkinson's disease associated protein alpha
synuclein. We showed that both proteins interact with selected glycolipids
through a common loop-shaped motif exhibiting little sequence homology. This 12
residue domain corresponded to fragments 34-45 of alpha-synuclein and 5-16 of
Abeta. By modulating the amino acid sequence of alpha-synuclein at only two
positions in which we introduced a pair of histidine residues found in Abeta, we
created a chimeric alpha-synuclein/Abeta peptide with extended ganglioside
binding properties. This chimeric peptide retained the property of alpha
synuclein to recognize GM3, and acquired the capacity to recognize GM1 (an Abeta
inherited characteristic). Free histidine (but not tryptophan or asparagine) and
Zn2+ (but not Na+) prevented this interaction, confirming the key role of His-13
and His-14 in ganglioside binding. Molecular dynamics studies suggested that the
chimeric peptide recognized cholesterol-constrained conformers of GM1, including
typical chalice-shaped dimers, that are representative of the condensed
cholesterol-ganglioside complexes found in lipid raft domains of the plasma
membrane of neural cells. Correspondingly, the peptide had a particular affinity
for raft-like membranes containing both GM1 and cholesterol. The chimeric peptide
also interacted with several other gangliosides, including major brain
gangliosides (GM4, GD1a, GD1b, and GT1b) but not with neutral glycolipids such as
GlcCer, LacCer or asialo-GM1. It could inhibit the binding of Abeta1-42 onto
neural SH-SY5Y cells and did not induce toxicity in these cells. In conclusion,
deciphering the glycolipid code of amyloid proteins allowed us to create a
universal ganglioside-binding peptide of only 12-residues with potential
therapeutic applications in infectious and neurodegenerative diseases that
involve cell surface gangliosides as receptors.
PMID- 25140900
TI - Rose Bengal acetate photodynamic therapy (RBAc-PDT) induces exposure and release
of Damage-Associated Molecular Patterns (DAMPs) in human HeLa cells.
AB - The new concept of Immunogenic Cell Death (ICD), associated with Damage
Associated Molecular Patterns (DAMPs) exposure and/or release, is recently
becoming very appealing in cancer treatment. In this context, PhotoDynamic
Therapy (PDT) can give rise to ICD and to immune response upon dead cells
removal. The list of PhotoSensitizers (PSs) able to induce ICD is still short and
includes Photofrin, Hypericin, Foscan and 5-ALA. The goal of the present work was
to investigate if Rose Bengal Acetate (RBAc), a powerful PS able to trigger
apoptosis and autophagy, enables photosensitized HeLa cells to expose and/or
release pivotal DAMPs, i.e. ATP, HSP70, HSP90, HMGB1, and calreticulin (CRT),
that characterize ICD. We found that apoptotic HeLa cells after RBAc-PDT exposed
and released, early after the treatment, high amount of ATP, HSP70, HSP90 and
CRT; the latter was distributed on the cell surface as uneven patches and co
exposed with ERp57. Conversely, autophagic HeLa cells after RBAc-PDT exposed and
released HSP70, HSP90 but not CRT and ATP. Exposure and release of HSP70 and
HSP90 were always higher on apoptotic than on autophagic cells. HMGB1 was
released concomitantly to secondary necrosis (24 h after RBAc-PDT). Phagocytosis
assay suggests that CRT is involved in removal of RBAc-PDT generated apoptotic
HeLa cells. Altogether, our data suggest that RBAc has all the prerequisites
(i.e. exposure and/or release of ATP, CRT, HSP70 and HSP90), that must be
verified in future vaccination experiments, to be considered a good PS candidate
to ignite ICD. We also showed tha CRT is involved in the clearance of RBAc
photokilled HeLa cells. Interestingly, RBAc-PDT is the first cancer PDT protocol
able to induce the translocation of HSP90 and plasma membrane co-exposure of CRT
with ERp57.
PMID- 25140901
TI - Determination and pharmacokinetic studies of arecoline in dog plasma by liquid
chromatography-tandem mass spectrometry.
AB - A rapid and sensitive high-performance liquid chromatography-tandem mass
spectrometry (LC-MS/MS) method was developed and validated for the determination
of arecoline concentration in dog plasma. Plasma sample was prepared by protein
precipitation using n-hexane (containing 1% isoamyl alcohol) with beta-pinene as
an internal standard. Chromatographic separation was achieved on an Agilent C18
column (4.6*75mm, 3.5MUm) using methanol: 5mM ammonium acetate as the mobile
phase with isocratic elution. Mass detection was carried out using positive
electrospray ionization in multiple reaction monitoring mode. The calibration
curve for arecoline was linear over a concentration range of 2-500ng/mL. The
intra-day and inter-day accuracy and precision were within the acceptable limits
of +/-10% at all concentrations. In summary, the LC-MS/MS method described herein
was fully validated and successfully applied to the pharmacokinetic study of
arecoline hydrobromide tablets in dogs after oral administration.
PMID- 25140902
TI - Influenza A virus protein PB1-F2 translocates into mitochondria via Tom40
channels and impairs innate immunity.
AB - Mitochondria contribute to cellular innate immunity against RNA viruses.
Mitochondrial-mediated innate immunity is regulated by signalling molecules that
are recruited to the mitochondrial membrane, and depends on the mitochondrial
inner membrane potential (Deltapsim). Here we examine the physiological relevance
of Deltapsim and the mitochondrial-associating influenza A viral protein PB1-F2
in innate immunity. When expressed in host cells, PB1-F2 completely translocates
into the mitochondrial inner membrane space via Tom40 channels, and its
accumulation accelerates mitochondrial fragmentation due to reduced Deltapsim. By
contrast, PB1-F2 variants lacking a C-terminal polypeptide, which is frequently
found in low pathogenic subtypes, do not affect mitochondrial function. PB1-F2
mediated attenuation of Deltapsim suppresses the RIG-I signalling pathway and
activation of NLRP3 inflammasomes. PB1-F2 translocation into mitochondria
strongly correlates with impaired cellular innate immunity, making this
translocation event a potential therapeutic target.
PMID- 25140903
TI - Stromal luteoma of the ovary: A rare ovarian pathology.
PMID- 25140904
TI - Use of multiple data sources and individual case investigation to refine
surveillance-based estimates of the HIV care continuum.
AB - OBJECTIVES: To assess the HIV care continuum among HIV-infected persons residing
in Seattle and King County, WA, at the end of 2011 and compare estimates of viral
suppression derived from different population-based data sources. METHODS: We
derived estimates for the HIV care continuum using a combination of HIV case and
laboratory surveillance data supplemented with individual investigation of cases
that seemed to be unlinked to or not retained in HIV care, a jurisdiction-wide
population-based retrospective chart review, and local data from the CDC's
Medical Monitoring Project and National HIV Behavioral Surveillance. RESULTS:
Adjusting for in- and out-migration of persons diagnosed with HIV, laboratory
surveillance data supplemented with individual case investigation suggest that
67% of persons diagnosed with HIV and 57% of all HIV-infected persons living in
King County at the end of 2011 were virally suppressed (plasma HIV RNA <200
copies/mL). The viral suppression estimates we derived from a population-based
chart review and adjusted local Medical Monitoring Project data were similar to
the surveillance-derived estimate and identical to each other (59% viral
suppression among all HIV-infected persons). CONCLUSIONS: The level of viral
suppression in King County is more than twice the national estimate and exceeds
estimates of control for other major chronic diseases in the United States. Our
findings suggest that national care continuum estimates may be substantially too
pessimistic and highlight the need to improve HIV surveillance data.
PMID- 25140905
TI - Low-level Viremia early in HIV infection.
AB - HIV RNA levels are usually high early in HIV infection. In the HPTN 061 study,
men were tested for HIV infection every 6 months; 6 (21.4%) of 28 men who
acquired HIV infection during the study had low or undetectable HIV RNA at the
time of HIV diagnosis. Antiretroviral drugs were not detected at the time of HIV
diagnosis. False-negative HIV test results were obtained for 2 men using multiple
assays. Antiretroviral drug resistance mutations were detected in HIV from 1 man.
Additional studies are needed to identify factors associated with low HIV RNA
levels during early HIV infection.
PMID- 25140906
TI - Impact of adherence and anthropometric characteristics on nevirapine
pharmacokinetics and exposure among HIV-infected Kenyan children.
AB - BACKGROUND: There are insufficient data on pediatric antiretroviral therapy (ART)
pharmacokinetics (PK), particularly for children in low- and middle-income
countries. METHODS: We conducted a prospective nevirapine (NVP) PK study among
HIV-infected Kenyan children aged 3-13 years initiating an NVP-based ART regimen.
NVP dose timing was measured through medication event monitors. Participants
underwent 2 inpatient assessments: 1 at 4-8 weeks after ART initiation and 1 at 3
4 months after ART initiation. Allometric scaling of oral clearance
(CL)/bioavailability (F) and volume of distribution (Vd)/F values were computed.
Nonlinear mixed-effects modeling using the first-order conditional estimation
with interaction method was performed with covariates. The impact of adherence on
time below minimum effective concentration was assessed in the final PK model
using medication event monitors data and model-estimated individual parameters.
RESULTS: Among 21 children enrolled, mean age was 5.4 years and 57% were female.
CL/F was 1.67 L/h and Vd/F was 3.8 L for a median child weighing 15 kg.
Participants' age had a significant impact on CL/F (P < 0.05), with an estimated
decrease in CL of 6.2% for each 1-year increase in age. Total body water
percentage was significantly associated with Vd/F (P < 0.001). No children had
>10% of time below minimum effective concentration when the PK model assumed
perfect adherence compared with 10 children when adherence data were used.
CONCLUSIONS: Age and body composition were significantly associated with
children's NVP PK parameters. ART adherence significantly impacted drug exposure
over time, revealing subtherapeutic windows that may lead to viral resistance.
PMID- 25140907
TI - Oligonucleotide ligation assay detects HIV drug resistance associated with
virologic failure among antiretroviral-naive adults in Kenya.
AB - BACKGROUND: Transmitted drug resistance (TDR) is increasing in some areas of
Africa. Detection of TDR may predict virologic failure of first-line
nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral
therapy (ART). We evaluated the utility of a relatively inexpensive
oligonucleotide ligation assay (OLA) to detect clinically relevant TDR at the
time of ART initiation. METHODS: Pre-ART plasmas from ART-naive Kenyans
initiating an NNRTI-based fixed-dose combination ART in a randomized adherence
trial conducted in 2006 were retrospectively analyzed by OLA for mutations
conferring resistance to NNRTI (K103N, Y181C, and G190A) and lamivudine (M184V).
Post-ART plasmas were analyzed for virologic failure (>=1000 copies/mL) at 6
month intervals over 18-month follow-up. Pre-ART plasmas of those with virologic
failure were evaluated for drug resistance by consensus and 454-pyrosequencing.
RESULTS: Among 386 participants, TDR was detected by OLA in 3.89% (95% confidence
interval: 2.19 to 6.33) and was associated with a 10-fold higher rate of
virologic failure (hazard ratio: 10.39; 95% confidence interval: 3.23 to 32.41; P
< 0.001) compared with those without TDR. OLA detected 24 TDR mutations (K103N: n
= 13; Y181C: n = 5; G190A: n = 3; M184V: n = 3) in 15 subjects (NNRTI: n = 15;
3TC: n = 3). Among 51 participants who developed virologic failure, consensus
sequencing did not detect additional TDR mutations conferring high-level
resistance, and pyrosequencing only detected additional mutations at frequencies
<2%. Mutant frequencies <2% at ART initiation were significantly less likely to
be found at the time of virologic failure compared with frequencies >=2% (22% vs.
63%; P < 0.001). CONCLUSIONS: Detection of TDR by a point mutation assay may
prevent the use of suboptimal ART.
PMID- 25140908
TI - Effects of an education and home-based pedometer walking program on ischemic
heart disease risk factors in people infected with HIV: a randomized trial.
AB - OBJECTIVE: People infected with the human immunodeficiency virus are at an
increased risk of developing ischemic heart disease (IHD); however, the effects
of an education and home-based pedometer walking program on risk factors of IHD
are not known. METHODS: We conducted a 12-month randomized study of an education
and home-based pedometer walking program in 84 human immunodeficiency virus
infected individuals with risk factors of IHD. RESULTS: Pedometer step count of
the control and intervention groups improved significantly (P = 0.03 for both
groups) at 6 months but was not significant at 12 months (P = 0.33 and 0.21,
respectively). Significant between-group effects were observed in 6-minute walk
test distance (P = 0.01), waist to hip ratio (P = 0.00), glucose (P = 0.00), and
high-density lipoprotein (P = 0.01) over the 12-month period. The program did not
result in change in high-sensitivity C-reactive protein as it was associated with
perceived stress (r = 0.23; P = 0.03), weight (r = 0.28; P = 0.01), body mass
index (r = 0.35; P < 0.00), waist (r = 0.28; P = 0.01) and hip circumference (r =
0.28; P = 0.01). Multivariate generalized estimation equation analysis
demonstrated an inverse association between interaction and perceived stress
(logB = -0.01; 95% confidence interval: -0.02 to -0.01; P <0.00) and body mass
index (logB = -0.02; 95% confidence interval: -0.03 to -0.002; P = 0.02) at group
level. CONCLUSION: An education and home-based pedometer walking program improves
physical activity levels, and beneficial changes in other IHD risk factors were
noted.
PMID- 25140909
TI - GSK1265744 pharmacokinetics in plasma and tissue after single-dose long-acting
injectable administration in healthy subjects.
AB - BACKGROUND: GSK1265744 (744) is an HIV-1 integrase inhibitor in clinical
development as a long-acting (LA) injectable formulation. This study evaluated
plasma and tissue pharmacokinetics after single-dose administration of 744 LA
administered by intramuscular (IM) or subcutaneous injections. METHODS: This was
a phase I, open-label, 9-cohort, parallel study of 744 in healthy subjects. 744
was administered as a 200 mg/mL nanosuspension at doses of 100-800 mg IM and 100
400 mg subcutaneous. RESULTS: Eight (6 active and 2 placebo) male and female
subjects participated in each of the first 7 cohorts. All 8 subjects, 4 males and
4 females, received active 744 LA in cohorts 8 and 9 and underwent rectal and
cervicovaginal tissue sampling, respectively. Plasma pharmacokinetic sampling was
performed for a minimum of 12 weeks or until 744 concentrations were <=0.1
MUg/mL. Rectal and cervicovaginal tissue biopsies were performed at weeks 2 and 8
(cohort 8) and weeks 4 and 12 (cohort 9). 744 LA was generally safe and well
tolerated after single injections. A majority of subjects reported injection site
reactions, all graded as mild in intensity. Plasma concentration-time profiles
were prolonged with measureable concentrations up to 52 weeks after dosing. 744
LA 800 mg IM achieved mean concentrations above protein adjusted-IC90 for
approximately 16 weeks. Rectal and cervicovaginal tissue concentrations ranged
from <8% to 28% of corresponding plasma concentrations. CONCLUSIONS: These data
suggest 744 LA injection has potential application as a monthly or less frequent
HIV treatment or prevention agent.
PMID- 25140911
TI - TNF receptors: signaling pathways and contribution to renal dysfunction.
AB - Tumor necrosis factor (TNF), initially reported to induce tumor cell apoptosis
and cachexia, is now considered a central mediator of a broad range of biological
activities from cell proliferation, cell death and differentiation to induction
of inflammation and immune modulation. TNF exerts its biological responses via
interaction with two cell surface receptors: TNFR1 and TNFR2. (TNFRs). These
receptors trigger shared and distinct signaling pathways upon TNF binding, which
in turn result in cellular outputs that may promote tissue injury on one hand but
may also induce protective, beneficial responses. Yet the role of TNF and its
receptors specifically in renal disease is still not well understood. This review
describes the expression of the TNFRs, the signaling pathways induced by them and
the biological responses of TNF and its receptors in various animal models of
renal diseases, and discusses the current outcomes from use of TNF biologics and
TNF biomarkers in renal disorders.
PMID- 25140913
TI - Endothelin-1, but not angiotensin II, induces afferent arteriolar myosin
diphosphorylation as a potential contributor to prolonged vasoconstriction.
AB - Bolus administration of endothelin-1 elicits long-lasting renal afferent
arteriolar vasoconstriction, in contrast to transient constriction induced by
angiotensin II. Vasoconstriction is generally evoked by myosin regulatory light
chain (LC20) phosphorylation at Ser19 by myosin light chain kinase (MLCK), which
is enhanced by Rho-associated kinase (ROCK)-mediated inhibition of myosin light
chain phosphatase (MLCP). LC20 can be diphosphorylated at Ser19 and Thr18,
resulting in reduced rates of dephosphorylation and relaxation. Here we tested
whether LC20 diphosphorylation contributes to sustained endothelin-1 but not
transient angiotensin II-induced vasoconstriction. Endothelin-1 treatment of
isolated arterioles elicited a concentration- and time-dependent increase in LC20
diphosphorylation at Thr18 and Ser19. Inhibition of MLCK or ROCK reduced
endothelin-1-evoked LC20 mono- and diphosphorylation. Pretreatment with an ETB
but not an ETA receptor antagonist abolished LC20 diphosphorylation, and an ETB
receptor agonist induced LC20 diphosphorylation. In contrast, angiotensin II
caused phosphorylation exclusively at Ser19. Thus, endothelin-1 and angiotensin
II induce afferent arteriolar constriction via LC20 phosphorylation at Ser19 due
to calcium activation of MLCK and ROCK-mediated inhibition of MLCP. Endothelin-1,
but not angiotensin II, induces phosphorylation of LC20 at Thr18. This could
contribute to the prolonged vasoconstrictor response to endothelin-1.
PMID- 25140912
TI - A systematic review and meta-analysis indicates underreporting of renal
dysfunction following endovascular aneurysm repair.
AB - Deterioration in renal function has been described after endovascular repair of
abdominal aortic aneurysms (EVRs). The etiology is multifactorial and represents
an important therapeutic target. A need exists to quantitatively summarize
incidence and severity of renal dysfunction after EVR to allow better-informed
attempts to preserve renal function and improve life expectancy. Here a
systematic search was performed using Medline and Embase for renal function after
EVR applying PRISMA statements. Univariate and multivariate random-effects meta
analyses were performed to estimate pooled postoperative changes in serum
creatinine and creatinine clearance at four time points after EVR. Clinically
relevant deterioration in renal function was also estimated at 1 year or more
after EVR. Pooled probability of clinically relevant deterioration in renal
function at 1 year or more was 18% (95% confidence interval of 14-23%, I2 of
82.5%). Serum creatinine increased after EVR by 0.05 mg/dl at 30 days/1 month,
0.09 mg/dl at 1 month to 1 year, and 0.11 mg/dl at 1 year or more (all
significant). Creatinine clearance decreased after EVR by 5.65 ml/min at 1 month
1 year and by 6.58 ml/min at 1 year or more (both significant). Thus, renal
dysfunction after EVR is common and merits attention.
PMID- 25140914
TI - Single functionalized graphene oxide reconstitutes kinesin mediated intracellular
cargo transport and delivers multiple cytoskeleton proteins and therapeutic
molecules into the cell.
AB - Here, we report a covalently functionalized graphene oxide with Tris-(nitrilo
Tris-acetic acid) (TGO), which can reconstitute kinesin mediated intracellular
cargo transport, and deliver multiple proteins and therapeutic antimitotic
dodecapeptide peptides into the cancer cell.
PMID- 25140915
TI - Storable N-phenylcarbamate palladacycles for rapid functionalization of an alkyne
encoded protein.
AB - Here we report the synthesis of storable N-phenylcarbamate palladacycles that
showed robust reactivity in the cross-coupling reaction with an alkyne-encoded
protein with a second-order rate constant approaching 19 770 +/- 930 M(-1) s(-1).
PMID- 25140916
TI - Synthesis of magnetically separable Ag3PO4/TiO2/Fe3O4 heterostructure with
enhanced photocatalytic performance under visible light for photoinactivation of
bacteria.
AB - Silver orthophosphate (Ag3PO4) is a low-band-gap photocatalyst that has received
considerable research interest in recent years. In this work, the magnetic
Ag3PO4/TiO2/Fe3O4 heterostructured nanocomposite was synthesized. The
nanocomposite was found to exhibit markedly enhanced photocatalytic activity,
cycling stability, and long-term durability in the photodegradation of acid
orange 7 (AO7) under visible light. Moreover, the antibacterial film prepared
from Ag3PO4/TiO2/Fe3O4 nanocomposite presented excellent bactericidal activity
and recyclability toward Escherichia coli (E. coli) cells under visible-light
irradiation. In addition to the intrinsic cytotoxicity of silver ions, the
elevated bactericidal efficiency of Ag3PO4/TiO2/Fe3O4 can be largely attributed
to its highly enhanced photocatalytic activity. The photogenerated hydroxyl
radicals and superoxide ions on the formed Ag/Ag3PO4/TiO2 interfaces cause
considerable morphological changes in the microorganism's cells and lead to the
death of the bacteria.
PMID- 25140917
TI - Large-scale synthesis of TiO2 microspheres with hierarchical nanostructure for
highly efficient photodriven reduction of CO2 to CH4.
AB - In this study, a simple and reproducible synthesis strategy was employed to
fabricate TiO2 microspheres with hierarchical nanostructure. The microspheres are
macroscopic in the bulk particle size (several hundreds to more than 1000 MUm),
but they are actually composed of P25 nanoparticles as the building units.
Although it is simple in the assembly of P25 nanoparticles, the structure of the
as-prepared TiO2 microspheres becomes unique because a hierarchical porosity
composed of macropores, larger mesopores (ca. 12.4 nm), and smaller mesopores
(ca. 2.3 nm) has been developed. The interconnected macropores and larger
mesopores can be utilized as fast paths for mass transport. In addition, this
hierarchical nanostructure may also contribute to some extent to the enhanced
photocatalytic activity due to increased multilight reflection/scattering.
Compared with the state-of-the-art photocatalyst, commercial Degussa P25 TiO2,
the as-prepared TiO2 microsphere catalyst has demonstrated significant
enhancement in photodriven conversion of CO2 into the end product CH4. Further
enhancement in photodriven conversion of CO2 into CH4 can be easily achieved by
the incorporation of metals such as Pt. The preliminary experiments with Pt
loading reveal that there is still much potential for considerable improvement in
TiO2 microsphere based photocatalysts. Most interestingly and significantly, the
synthesis strategy is simple and large quantity of TiO2 microspheres (i.e.,
several hundred grams) can be easily prepared at one time in the lab, which makes
large-scale industrial synthesis of TiO2 microspheres feasible and less
expensive.
PMID- 25140919
TI - The Grief and Meaning Reconstruction Inventory (GMRI): Initial Validation of a
New Measure.
AB - Although increasing numbers of grief theorists, researchers, and therapists have
begun to focus on the quest for meaning in lives disrupted by loss, no convenient
and psychometrically validated measure of meanings made specifically in
bereavement has been available to guide their efforts. To construct such a
measure, the authors began with a systematic content analysis of sense-making,
benefit finding, and identity reconstruction themes gleaned from the narrative
responses of a sample of 162 adults who were diverse in their age, ethnicity,
relationship to the decedent, cause of death, and severity of their grief
response. These were then formulated into a set of 65 candidate items in a Likert
scale format representing the level of the respondent's endorsement of the item
in the past week. Subsequent administration to a second sample of 300 bereaved
respondents permitted factor analysis of this pilot version of the Grief and
Meaning Reconstruction Inventory (GMRI), and reduced the items to 29, which
loaded on 5 distinct factors, labeled Continuing Bonds, Personal Growth, Sense of
Peace, Emptiness and Meaninglessness, and Valuing Life. Both the overall GMRI and
its constituent factors showed good internal consistency and strong convergent
validity in the form of negative correlations with established measures of
bereavement-related negative emotions, symptoms of complicated grief, and more
general psychological distress and mental health symptomatology, and positive
correlations with grief related personal growth. The authors close by noting
several specific research and clinical applications of the measure, which could
play a useful role in testing and refining contemporary models of meaning made in
the wake of loss.
PMID- 25140920
TI - Driving forces for the self-assembly of graphene oxide on organic monolayers.
AB - Graphene oxide (GO) flakes were self-assembled from solution on surfaces of self
assembled monolayers (SAMs), varying in the chemical structure of their head
groups. The coverage density of GO relates to strength of attractive interaction,
which is largest for Coulomb interaction provided by positively charged SAM head
groups and negatively charged GO. A rough surface enhances the coverage density
but with the same trend in driving force dependency. The self-assembly approach
was used to fabricate field-effect transistors with reduced GO (rGO) as active
layer. The SAMs as attractive layer for self-assembly remain almost unaffected by
the reduction from GO to rGO and serve as ultra-thin gate dielectrics in devices,
which operate at low voltages of maximum 3 V and exhibit a shift of the Dirac
voltage related to the dipole moment of the SAMs.
PMID- 25140921
TI - Maternal distress in early life predicts the waist-to-hip ratio in
schoolchildren.
AB - We report on life course stress determinants of overweight in children, using
data from the longitudinal follow-up of the nested case-control arm of the SAGE
(study of asthma genes and the environment) birth cohort in Manitoba, Canada.
Waist and hip measurements were obtained during a clinic visit at age 9-11 years.
Multiple linear regression was conducted to determine the relationship between
the waist-to-hip ratio and maternal smoking during pregnancy, postpartum maternal
distress and stress reactivity in children (cortisol, cortisol-DHEA
[dihydroepiandrostrenone] ratio quartiles) following a clinic stressor at age 8
10 years. We found waist-to-hip risk at age 9-11 years to be elevated among boys
and girls whose mothers had experienced distress in the postnatal period. This
association varied by gender and asthma status. In healthy girls, postpartum
distress increased waist-to-hip ratio by a factor of 0.034 (P < 0.01),
independent of the child's stage of puberty and adrenarche, cortisol-DHEA ratio
and duration of exclusive breastfeeding. Among girls with asthma, maternal
smoking during pregnancy was associated with an increased waist-to-hip ratio, if
the mother also experienced distress in the postpartum period (0.072, P = 0.038).
Among asthmatic boys, an association between maternal distress and waist-to-hip
ratio was evident at the highest cortisol-DHEA ratios. Stress-induced changes to
leptin and infant over-eating pathways were proposed to explain the postnatal
maternal distress effects. Drawing on the theories of evolutionary biology, our
findings underscore the significance of postnatal stress in disrupting
hypothalamic-pituitary-adrenal axis function in infants and increasing risk for
child overweight.
PMID- 25140922
TI - Pregnancy and neonatal outcomes following hyperemesis gravidarum.
AB - Undernutrition during pregnancy is associated with detrimental pregnancy and
neonatal outcomes, which can have long-term implications for the infant.
Hyperemesis gravidarum may severely limit nutritional intake. The aim of this
study was to investigate the effect of hyperemesis on pregnancy and neonatal
outcome, particularly gestation length and infant size at birth. Seventy-five
prospectively recruited women admitted to a tertiary level hospital in Auckland,
with hyperemesis gravidarum between March 2003 and October 2005, were compared to
142 controls matched for age, parity, ethnicity and expected date of delivery.
Data were obtained from electronic records and analysed by Student's t-test,
chi2, Wilcoxon, Fisher's exact tests and linear regression. Length of gestation,
birth weight and crown-heel length were not different between participants and
controls. Infants born to women with hyperemesis gravidarum had smaller head
circumferences (Z-score mean (s.d.) 0.02 (0.16) v. 0.43 (0.11), P = 0.04 in all
infants and -0.02 (1.24) v. 0.48 (1.29), P = 0.01 in-term infants). This study
found hyperemesis gravidarum to be associated with smaller head circumferences in
offspring. Given the reported associations between smaller head circumference at
birth and lower cognitive ability and higher risk of cardiovascular disease in
later life, further study is necessary to confirm these results and to determine
whether there are any long-term implications for the offspring.
PMID- 25140923
TI - Cord blood immune biomarkers in small for gestational age births.
AB - Fetal growth restriction is a risk factor for development of adulthood diseases,
but the biological mechanism of this association remains unknown. Limited
biomarkers have been studied in settings of preterm birth and maternal
inflammation, but the relationship between a wide range of immune biomarkers and
fetal growth has not been studied. The hypothesis of this study was that fetal
growth restriction is associated with altered immune biomarker levels. We
examined the relationship between small for gestational age (SGA) status and 27
umbilical cord blood immune biomarkers. This study was part of a large-scale
cohort study of preterm birth and low birth weight conducted at Boston Medical
Center, an inner city, predominantly minority patient population. Growth status
was determined based on birth weight standardized to an internal reference. There
were 74 SGA births and 319 appropriate for age (AGA) births with complete
clinical and biomarker data. Adjusting for covariates and using AGA as reference,
SGA births had lower levels of log IL-1beta (ng/l; beta -0.38, 95% CI -0.57,
0.19, P < 0.01), log BDNF (beta -0.29, 95% CI -0.55, -0.03, P < 0.05) and log NT
3 (beta -0.46, 95% CI -0.77, -0.15, P < 0.01). No associations were found between
other biomarkers and SGA. In conclusion, three biomarkers were selectively
associated with SGA status. Our results provide information that could be used to
guide additional studied aimed at determining mechanisms that contribute to fetal
growth.
PMID- 25140924
TI - Pre- and postnatal determinants of childhood body size: cohort and sibling
analyses.
AB - Growing evidence suggests obesity may have its roots in early life but it is
still uncertain whether prenatal factors operate primarily though altering early
infant growth. It is also still unclear if rapid growth during selected time
periods is more important than other time periods in predicting future body size.
Using prospectively collected data on 20,523 participants born from 1959 to 1966
(10,327 boys; 10,196 girls) of the Collaborative Perinatal Project, we
investigated the associations between pre- and postnatal factors and childhood
body size at age 7 years and compared these associations across linear, logistic
and quantile regression models. Maternal body mass index (BMI), maternal
pregnancy weight gain, birth weight and postnatal weight change for three time
periods (birth to 4 months; 4-12 months; 1-4 years) were all positively and
independently associated with BMI at age 7 years. Rapid growth during each time
period had a similar association BMI at age 7 years. For example, a 10-percentile
increase in weight increased the probability of being overweight at age 7 years
by approximately two-fold regardless of time period (OR = 1.8-2.2 for boys and
girls). Using same-sex siblings (n = 571 boy sets; n = 651 girl sets) from the
same cohort, we observed that siblings with higher BMI at age 7 years than their
same-sex siblings were more likely to have higher maternal pregnancy weight gain,
higher maternal pre-pregnancy BMI, higher birth weight and increased rate of
weight gain during the three time periods. These consistent findings both from
the overall cohort and the sibling analyses suggest that there are multiple,
rather than specific critical periods of influence shaping childhood body size.
PMID- 25140925
TI - Perinatal programming of murine immune responses by polyunsaturated fatty acids.
AB - Linoleic acid and alpha-linolenic acid are essential fatty acids (eFAs) and have
to be acquired from the diet. eFAs are the precursors for long-chain
polyunsaturated fatty acids (lcPUFAs), which are important immune-modulating
compounds. lcPUFAs can be converted into eicosanoids and other mediators. They
affect membrane structure and fluidity and can alter gene expression. There has
been a marked change in dietary fatty acid intake over the last several decades.
Since eFAs are acquired from the diet and immune development occurs mainly
perinatally, the maternal diet may influence fetal and neonatal eFA levels, and
thereby lcPUFA status, and thus immune development and function. To study whether
early exposure to eFAs can program immune function, mice were fed diets varying
in the ratio of omega-3 to omega-6-eFAs during pregnancy and/or lactation. After
weaning, pups received a Western-style diet. At 11 weeks of age, the effects of
maternal diet on the offspring's allergic and vaccination responses were examined
using the T-helper 2 driven ovalbumin-induced allergy model and the T-helper 1
driven influenza-vaccination model, respectively. Offspring of dams fed a high
alpha-linolenic acid diet during lactation showed an enhanced vaccination
response. As diets with either low or high omega-3/omega-6-eFA ratio attenuated
the T-helper 2 allergic response, the high alpha-linolenic acid diet fed during
lactation had the most pronounced effect. These results indicate that there is a
programming effect of maternal diet on the offspring's immune response and that
in mice the window of greatest susceptibility to maternal dietary intervention is
the lactation/suckling period.
PMID- 25140926
TI - Maternal malnutrition and placental insufficiency induce global downregulation of
gene expression in fetal kidneys.
AB - Malnutrition during pregnancy causes intrauterine growth restriction and long
term changes in the offspring's physiology and metabolism. To explore molecular
mechanisms by which the intrauterine environment conveys programming in fetal
kidneys, an organ known to undergo substantial changes in many animal models of
late gestational undernutrition, we used a microswine model of maternal protein
restriction (MPR) in which sows were exposed to isocaloric low protein (LP) diet
during late gestation/early lactation to encompass the bulk of nephrogenesis. To
define general v. model-specific effects, we also used a sheep model of placental
insufficiency. In kidneys from near-term fetal and neonatal microswine LP
offspring, per cell levels of total RNA, poly(A)+ mRNA and transcripts of several
randomly chosen housekeeping genes were significantly reduced compared to
controls. Microarray analysis revealed only a few MPR-resistant genes that escape
such downregulation. The ratio of histone modifications H3K4m3/H3K9m3
(active/silenced) was reduced at promoters of downregulated but not MPR-resistant
genes suggesting that transcriptional suppression is the point of control. In
juvenile offspring, on a normal diet from weaning, cellular RNA levels and
histone mark patterns were recovered to near control levels, indicating that
global repression of transcription is dependent on ongoing MPR. Importantly,
cellular RNA content was also reduced in ovine fetal kidneys during placental
insufficiency. These studies show that global repression of transcription may be
a universal consequence of a poor intrauterine environment that contributes to
fetal restriction.
PMID- 25140927
TI - Attitudes towards microbicide use for bacterial vaginosis in pregnancy.
AB - Background Bacterial vaginosis (BV) is the most common reproductive tract
infection (RTI) and is a significant risk factor for preterm birth. Microbicides
could be an option for the prevention and treatment of BV in pregnancy, and
understanding use of the product will be crucial. The present study explored
attitudes of women in the third trimester of pregnancy regarding topical
microbicide use for the prevention and treatment of BV. METHODS: Twenty-six women
in their third trimester were interviewed regarding their knowledge and beliefs
about RTIs during pregnancy and attitudes concerning the use of topical
microbicides for prevention and treatment of BV. RESULTS: Participants had a mean
age of 24.9 years, were largely under-represented minorities and the majority had
had past pregnancies. Participants had knowledge and experience with RTIs but not
BV. They were open to the use of microbicides for prevention or treatment of BV,
but believed that women requiring treatment would be more motivated. Rationales
for acceptability were most commonly related to the baby's health. Practical
issues that may interfere with use were often, but not always, related to
pregnancy. There was a range of attitudes about partner involvement in decision
making and the practicalities of product use. CONCLUSION: Pregnant women are
knowledgeable about RTIs but not necessarily BV. The women in this study found
microbicide use acceptable, particularly for treatment. To improve acceptability
and use, education would be needed about BV and possible complications, how to
overcome practical problems and the value of involving partners in the decision.
PMID- 25140928
TI - Discussion of the influence of CO and CH4 in CO2 transport, injection, and
storage for CCS technology.
AB - This paper discusses the influence of the noncondensable impurities CO and CH4 on
Carbon Capture and Storage (CCS) technology. We calculated and drew conclusions
about the impact of both impurities in the CO2 on selected transport, injection,
and storage parameters (pipeline pressure drop, storage capacity, etc.), whose
analysis is necessary for the safe construction and operation of CO2 pipelines
and for the secure long-term geological storage of anthropogenic CO2. To
calculate these parameters, it is necessary to acquire data on the volumetric
properties and the vapor-liquid equilibrium of the fluid being subjected to CCS.
In addition to literature data, we used new experimental data, which are
presented here and were obtained for five mixtures of CO2+CO with compositions
characteristic of the typical emissions of the E.U. and the U.S.A. Temperatures
and pressures are based on relevant CO2 pipeline and geological storage site
values. From our experimental results, Peng-Robinson, PC-SAFT, and GERG Equations
of State for were validated CO2+CO under the conditions of CCS. We conclude that
the concentration of both impurities strongly affects the studied parameters,
with CO being the most influential and problematic. The overall result of these
negative effects is an increase in the difficulties, risks, and overall costs of
CCS.
PMID- 25140929
TI - Novel G3/DT adjuvant promotes the induction of protective T cells responses after
vaccination with a seasonal trivalent inactivated split-virion influenza vaccine.
AB - Vaccines used against seasonal influenza are poorly effective against influenza A
viruses of novel subtypes that may have pandemic potential. Furthermore,
pre(pandemic) influenza vaccines are poorly immunogenic, which can be overcome by
the use of adjuvants. A limited number of adjuvants has been approved for use in
humans, however there is a need for alternative safe and effective adjuvants that
can enhance the immunogenicity of influenza vaccines and that promote the
induction of broad-protective T cell responses. Here we evaluated a novel
nanoparticle, G3, as an adjuvant for a seasonal trivalent inactivated influenza
vaccine in a mouse model. The G3 adjuvant was formulated with or without steviol
glycosides (DT, for diterpenoid). The use of both formulations enhanced the virus
specific antibody response to all three vaccine strains considerably. The
adjuvants were well tolerated without any signs of discomfort. To assess the
protective potential of the vaccine-induced immune responses, an antigenically
distinct influenza virus strain, A/Puerto Rico/8/34 (A/PR/8/34), was used for
challenge infection. The vaccine-induced antibodies did not cross-react with
strain A/PR/8/34 in HI and VN assays. However, mice immunized with the G3/DT
adjuvanted vaccine were partially protected against A/PR/8/34 infection, which
correlated with the induction of anamnestic virus-specific CD8(+) T cell
responses that were not observed with the use of G3 without DT. Both formulations
induced maturation of human dendritic cells and promoted antigen presentation to
a similar extent. In conclusion, G3/DT is a promising adjuvant formulation that
not only potentiates the antibody response induced by influenza vaccines, but
also induces T cell immunity which could afford broader protection against
antigenically distinct influenza viruses.
PMID- 25140930
TI - Humoral responses to independent vaccinations are correlated in healthy boosted
adults.
AB - BACKGROUND: Roughly half of U.S. adults do not receive recommended booster
vaccinations, but protective antibody levels are rarely measured in adults.
Demographic factors, vaccination history, and responses to other vaccinations
could help identify at-risk individuals. We sought to characterize rates of
seroconversion and determine associations of humoral responses to multiple
vaccinations in healthy adults. METHODS: Humoral responses toward measles, mumps,
tetanus toxoid, pertussis, hepatitis B surface antigen, and anthrax protective
antigen were measured by ELISA in post-immunization samples from 1465 healthy
U.S. military members. We examined the effects of demographic and clinical
factors on immunization responses, as well as assessed correlations between
vaccination responses. RESULTS: Subsets of boosted adults did not have
seroprotective levels of antibodies toward measles (10.4%), mumps (9.4%),
pertussis (4.7%), hepatitis B (8.6%) or protective antigen (14.4%) detected. Half
lives of antibody responses were generally long (>30 years). Measles and mumps
antibody levels were correlated (r=0.31, p<0.001), but not associated with select
demographic features or vaccination history. Measles and mumps antibody levels
also correlated with tetanus antibody response (r=0.11, p<0.001). CONCLUSIONS:
Vaccination responses are predominantly robust and vaccine specific. However, a
small but significant portion of the vaccinated adult population may not have
quantitative seroprotective antibody to common vaccine-preventable infections.
PMID- 25140931
TI - Bilateral high- and low-frequency rTMS in acute stroke patients with hemiparesis:
a comparative study with unilateral high-frequency rTMS.
AB - BACKGROUND: High- and low-frequency repetitive transcranial magnetic stimulation
(HF-rTMS and LF-rTMS) has been shown to be beneficial for upper limb hemiparesis
in patients with acute stroke. However, no study has examined the usefulness of
bilateral application of HF- and LF-rTMS (BL-rTMS). METHODS: Fifty-eight
hemiparetic patients with acute stroke were randomly assigned into two groups: HF
rTMS group and BL-rTMS group. All patients were scheduled to receive five
sessions of either HF-rTMS over the lesional hemisphere or BL-rTMS over both
hemispheres for 5 days. Motor function of the affected upper limb was evaluated
using the Brunnstrom Recovery Stage (BRS) for upper-limb and hand-fingers, grip
strength and tapping frequency, before the first session and after the last
session of rTMS. RESULTS: Improvement of BRS for the upper limb and hand/finger
was significantly greater in the BL-rTMS group than the HF-rTMS group (p < 0.01).
Improvement in grip strength and tapping frequency was also greater in the BL
rTMS group, although the differences were not statistically significant.
CONCLUSIONS: The proposed BL-rTMS is safe and feasible and showed a greater
improvement of BRS of the affected upper limb compared to HF-rTMS. This novel
rTMS approach may be a useful intervention for hemiparetic patients with acute
stroke.
PMID- 25140932
TI - Physician-assisted suicide: a matter of choice.
PMID- 25140934
TI - Finding the courage to seek care.
PMID- 25140935
TI - ID badges: what's really in a name?
PMID- 25140936
TI - A tale of two hospital systems: preparing new graduates for clinical practice.
PMID- 25140937
TI - Introducing nursing informatics.
PMID- 25140938
TI - Spotlight on nurse researcher Kimberly Stephens.
PMID- 25140942
TI - Patient education. Angina.
PMID- 25140943
TI - Learning self-advocacy.
PMID- 25140944
TI - How clinical nurse leaders can improve rural healthcare.
PMID- 25140945
TI - Intracolonic administration of vancomycin for Clostridium difficile infection.
PMID- 25140946
TI - Professional perspectives on planned home births.
PMID- 25140947
TI - Make carbohydrate counting add up.
PMID- 25140949
TI - Fighting bed alarm fatigue in orthopedic units.
PMID- 25140950
TI - Ebola virus disease: an emerging threat.
PMID- 25140952
TI - FDA approval of bedaquiline--the benefit-risk balance for drug-resistant
tuberculosis.
PMID- 25140953
TI - Did hospital engagement networks actually improve care?
PMID- 25140954
TI - The impact and evolution of Medicare Part D.
PMID- 25140955
TI - The challenges of challenge experiments.
PMID- 25140956
TI - Controlled trial of transfusions for silent cerebral infarcts in sickle cell
anemia.
AB - BACKGROUND: Silent cerebral infarcts are the most common neurologic injury in
children with sickle cell anemia and are associated with the recurrence of an
infarct (stroke or silent cerebral infarct). We tested the hypothesis that the
incidence of the recurrence of an infarct would be lower among children who
underwent regular blood-transfusion therapy than among those who received
standard care. METHODS: In this randomized, single-blind clinical trial, we
randomly assigned children with sickle cell anemia to receive regular blood
transfusions (transfusion group) or standard care (observation group).
Participants were between 5 and 15 years of age, with no history of stroke and
with one or more silent cerebral infarcts on magnetic resonance imaging and a
neurologic examination showing no abnormalities corresponding to these lesions.
The primary end point was the recurrence of an infarct, defined as a stroke or a
new or enlarged silent cerebral infarct. RESULTS: A total of 196 children (mean
age, 10 years) were randomly assigned to the observation or transfusion group and
were followed for a median of 3 years. In the transfusion group, 6 of 99 children
(6%) had an end-point event (1 had a stroke, and 5 had new or enlarged silent
cerebral infarcts). In the observation group, 14 of 97 children (14%) had an end
point event (7 had strokes, and 7 had new or enlarged silent cerebral infarcts).
The incidence of the primary end point in the transfusion and observation groups
was 2.0 and 4.8 events, respectively, per 100 years at risk, corresponding to an
incidence rate ratio of 0.41 (95% confidence interval, 0.12 to 0.99; P=0.04).
CONCLUSIONS: Regular blood-transfusion therapy significantly reduced the
incidence of the recurrence of cerebral infarct in children with sickle cell
anemia. (Funded by the National Institute of Neurological Disorders and Stroke
and others; Silent Cerebral Infarct Multi-Center Clinical Trial
ClinicalTrials.gov number, NCT00072761, and Current Controlled Trials number,
ISRCTN52713285.).
PMID- 25140957
TI - Oral GS-5806 activity in a respiratory syncytial virus challenge study.
AB - BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of infant
hospitalizations and is increasingly recognized as a cause of considerable
morbidity and mortality. No accepted antiviral treatment exists. METHODS: We
conducted a double-blind, placebo-controlled study of GS-5806, an oral RSV-entry
inhibitor, in healthy adults who received a clinical challenge strain of RSV
intranasally. Participants were monitored for 12 days. At the time of a positive
test for RSV infection or 5 days after inoculation, whichever occurred first,
participants were randomly assigned to receive GS-5806 or placebo in one of seven
sequential cohorts. Cohorts 1 to 4 received a first dose of 50 mg of GS-5806 and
then 25 mg daily for the next 4 days, cohort 5 received a first dose of 50 mg and
then 25 mg daily for the next 2 days, cohort 6 received one 100-mg dose, and
cohort 7 received a first dose of 10 mg and then 5 mg daily for the next 4 days.
Dose selection for cohorts 5, 6, and 7 occurred after an interim analysis of data
for cohorts 1 to 4. The primary end point was the area under the curve (AUC) for
the viral load, which was assessed after administration of the first dose through
the 12th day after inoculation. Secondary end points were mucus weight and
symptom scores. RESULTS: Among the 54 participants in cohorts 1 to 4 who were
infected with RSV, active treatment was associated with a lower viral load
(adjusted mean, 250.7 vs. 757.7 log10 plaque-forming-unit equivalents [PFUe] *
hours per milliliter; P<0.001), lower total mucus weight (mean, 6.9 g vs. 15.1 g;
P=0.03), and a lower AUC for the change from baseline in symptom scores (adjusted
mean, -20.2 vs. 204.9 * hours; P=0.005). The results were similar in cohorts 5,
6, and 7. Adverse events, including low neutrophil counts and increased levels of
alanine aminotransferase, were more common among participants receiving GS-5806.
CONCLUSIONS: Treatment with GS-5806 reduced the viral load and the severity of
clinical disease in a challenge study of healthy adults. (Funded by Gilead
Sciences; ClinicalTrials.gov number, NCT01756482.).
PMID- 25140958
TI - Multidrug-resistant tuberculosis and culture conversion with bedaquiline.
AB - BACKGROUND: Bedaquiline (Sirturo, TMC207), a diarylquinoline that inhibits
mycobacterial ATP synthase, has been associated with accelerated sputum-culture
conversion in patients with multidrug-resistant tuberculosis, when added to a
preferred background regimen for 8 weeks. METHODS: In this phase 2b trial, we
randomly assigned 160 patients with newly diagnosed, smear-positive, multidrug
resistant tuberculosis to receive either 400 mg of bedaquiline once daily for 2
weeks, followed by 200 mg three times a week for 22 weeks, or placebo, both in
combination with a preferred background regimen. The primary efficacy end point
was the time to sputum-culture conversion in liquid broth. Patients were followed
for 120 weeks from baseline. RESULTS: Bedaquiline reduced the median time to
culture conversion, as compared with placebo, from 125 days to 83 days (hazard
ratio in the bedaquiline group, 2.44; 95% confidence interval, 1.57 to 3.80;
P<0.001 by Cox regression analysis) and increased the rate of culture conversion
at 24 weeks (79% vs. 58%, P=0.008) and at 120 weeks (62% vs. 44%, P=0.04). On the
basis of World Health Organization outcome definitions for multidrug-resistant
tuberculosis, cure rates at 120 weeks were 58% in the bedaquiline group and 32%
in the placebo group (P=0.003). The overall incidence of adverse events was
similar in the two groups. There were 10 deaths in the bedaquiline group and 2 in
the placebo group, with no causal pattern evident. CONCLUSIONS: The addition of
bedaquiline to a preferred background regimen for 24 weeks resulted in faster
culture conversion and significantly more culture conversions at 120 weeks, as
compared with placebo. There were more deaths in the bedaquiline group than in
the placebo group. (Funded by Janssen Pharmaceuticals; TMC207-C208
ClinicalTrials.gov number, NCT00449644.).
PMID- 25140959
TI - Somatic mutations in cerebral cortical malformations.
AB - BACKGROUND: Although there is increasing recognition of the role of somatic
mutations in genetic disorders, the prevalence of somatic mutations in
neurodevelopmental disease and the optimal techniques to detect somatic mosaicism
have not been systematically evaluated. METHODS: Using a customized panel of
known and candidate genes associated with brain malformations, we applied
targeted high-coverage sequencing (depth, >=200*) to leukocyte-derived DNA
samples from 158 persons with brain malformations, including the double-cortex
syndrome (subcortical band heterotopia, 30 persons), polymicrogyria with
megalencephaly (20), periventricular nodular heterotopia (61), and pachygyria
(47). We validated candidate mutations with the use of Sanger sequencing and, for
variants present at unequal read depths, subcloning followed by colony
sequencing. RESULTS: Validated, causal mutations were found in 27 persons (17%;
range, 10 to 30% for each phenotype). Mutations were somatic in 8 of the 27
(30%), predominantly in persons with the double-cortex syndrome (in whom we found
mutations in DCX and LIS1), persons with periventricular nodular heterotopia
(FLNA), and persons with pachygyria (TUBB2B). Of the somatic mutations we
detected, 5 (63%) were undetectable with the use of traditional Sanger sequencing
but were validated through subcloning and subsequent sequencing of the subcloned
DNA. We found potentially causal mutations in the candidate genes DYNC1H1, KIF5C,
and other kinesin genes in persons with pachygyria. CONCLUSIONS: Targeted
sequencing was found to be useful for detecting somatic mutations in patients
with brain malformations. High-coverage sequencing panels provide an important
complement to whole-exome and whole-genome sequencing in the evaluation of
somatic mutations in neuropsychiatric disease. (Funded by the National Institute
of Neurological Disorders and Stroke and others.).
PMID- 25140960
TI - Aortic-valve stenosis--from patients at risk to severe valve obstruction.
PMID- 25140961
TI - Cancer of unknown primary site.
PMID- 25140962
TI - Images in clinical medicine. Intraoral presentation of antrochoanal polyp.
PMID- 25140963
TI - Case records of the Massachusetts General Hospital. Case 26-2014. A 21-month-old
boy with lethargy, respiratory distress, and abdominal distention.
PMID- 25140964
TI - More blood for sickle cell anemia?
PMID- 25140965
TI - Progress in the prevention and treatment of RSV infection.
PMID- 25140966
TI - Molecular basis of giant cells in tuberous sclerosis complex.
PMID- 25140967
TI - Treatments for idiopathic pulmonary fibrosis.
PMID- 25140968
TI - Treatments for idiopathic pulmonary fibrosis.
PMID- 25140969
TI - Treatments for idiopathic pulmonary fibrosis.
PMID- 25140970
TI - Treatments for idiopathic pulmonary fibrosis.
PMID- 25140971
TI - Treatments for idiopathic pulmonary fibrosis.
PMID- 25140972
TI - The metabolic syndrome and DYRK1B.
PMID- 25140973
TI - The metabolic syndrome and DYRK1B.
PMID- 25140974
TI - The metabolic syndrome and DYRK1B.
PMID- 25140975
TI - The metabolic syndrome and DYRK1B.
PMID- 25140976
TI - Images in clinical medicine. Posterior mediastinal mass.
PMID- 25140977
TI - Interactive medical case. A man with fever, cough, and rash.
PMID- 25140978
TI - Prevalence and characterization of antimicrobial-resistant Escherichia coli
isolated from conventional and organic vegetables.
AB - To compare the characteristics and to identify the epidemiological relationships
of Escherichia coli isolated from organic and conventional vegetables, the
antimicrobial resistance and genetic properties of E. coli were investigated from
2010 to 2011. E. coli was isolated from 1 of 111 (0.9%) organic vegetables and
from 20 of 225 (8.9%) conventional vegetables. The majority of strains were
isolated from the surrounding farming environment (n=27/150 vs. 49/97 in organic
vs. conventional samples). The majority of the vegetable strains were isolated
from the surrounding farming environments. E. coli isolated from organic
vegetables showed very low antimicrobial resistance rates except for cephalothin,
ranging from 0% to 17.9%, while the resistance rates to cephalothin (71%) were
extremely high in both groups. E. coli isolates expressed various resistance
genes, which most commonly included blaTEM, tet(A), strA, strB, and qnrS.
However, none of the isolates harbored tet(D), tet(E), tet(K), tet(L), tet(M), or
qnrA. The transferability of tet gene, tet(A), and tet(B) was identified in
tetracycline-resistant E. coli, and the genetic relationship was confirmed in a
few cases from different sources. With regard to the lower antimicrobial
resistance found in organic produce, this production mode seems able to
considerably reduce the selection of antimicrobial-resistant bacteria on
vegetables.
PMID- 25140979
TI - Spontaneous abortion and functional polymorphism (Val16Ala) in the manganese SOD
gene.
AB - Spontaneous abortion is the most common complication of early pregnancy. Genetic
factors have been hypothesised to play a role in spontaneous abortion. Since it
is possible that the balance of oxidants and antioxidants can be affected by
different genetic variants, gene polymorphisms have been proposed as a
susceptibility factor that increases the chance of miscarriage. Manganese
superoxide dismutase is an important antioxidant enzyme encoded by manganese
superoxide dismutase (MnSOD) gene. The aim of this experiment was to assess
whether Val16Ala polymorphism of MnSOD gene is associated with miscarriage in
northern Iran. Polymerase chain reaction-restriction fragment length polymorphism
(PCR-RFLP) was used for genotyping. Statistical analyses were conducted using the
chi(2)-test. The genetic distributions did not differ significantly between cases
and controls, however slightly more Val/Val genotypes were found among the
patients compared with control subjects (p = 0.059). No correlation was observed
between susceptibility to abortion and MnSOD Val16Ala polymorphism. Larger
population-based studies are needed for clarifying the relationship between
abortion and MnSOD genotypes.
PMID- 25140980
TI - Motivational interviewing for alcohol misuse in young adults.
AB - BACKGROUND: Globally, harmful use of alcohol results in approximately 2.5 million
deaths each year. About 9% of these deaths are young people between the ages of
15 and 29 years (WHO 2011), mainly resulting from motor vehicle accidents,
homicides, suicides and drownings. Hazardous drinking levels for men (consuming
over 40 g/day alcohol on average, that is 5 units) double the risk of liver
disease, raised blood pressure, some cancers and violent death (because some
people who have this average alcohol consumption drink heavily on some days). For
women, over 24 g/day average alcohol consumption (3 units) increases the risk for
developing liver disease and breast cancer. Motivational interviewing (MI) is a
popular technique for addressing excessive drinking in young adults but its
effectiveness has not previously been examined in a Cochrane review. OBJECTIVES:
The specific objectives were:(1) to summarise current evidence about the effects
of MI intended to address alcohol and alcohol-related problems in young adults,
compared with no intervention or a different intervention, on alcohol consumption
and other substantive outcome measures;(2) to investigate whether the effects of
MI are modified by the length of the intervention. SEARCH METHODS: Relevant
evidence was identified from (1) Cochrane Central Register of Controlled Trials
(CENTRAL) (October 2013), (2) MEDLINE (January 1966 to October 2013), (3) EMBASE
(January 1988 to October 2013), and (4) PsycINFO (1985 to October 2013).
References of topic-related systematic reviews and the included studies were
handsearched. SELECTION CRITERIA: Randomised controlled trials and cluster
randomised controlled trials of young people up to the age of 25 years in college
and non-college settings comparing MIs with no intervention or a different
intervention for prevention of alcohol misuse and alcohol-related problems were
included. DATA COLLECTION AND ANALYSIS: We used the standard methodological
procedures expected by The Cochrane Collaboration. MAIN RESULTS: A total of 66
randomised trials (17,901 participants) were included four of which were cluster
randomised. Studies with longer-term follow-up (four plus months) were of more
interest when considering the sustainability of intervention effects.At four or
more months follow-up, effects were found for the quantity of alcohol consumed
(standardised mean difference (SMD) -0.14; 95% confidence interval (CI) -0.20 to
0.08 or a reduction from 13.7 drinks/week to 12.2 drinks/week), moderate quality
of evidence; frequency of alcohol consumption (SMD -0.11; 95% CI -0.19 to -0.03
or a reduction in the number of days/week alcohol was consumed from 2.74 days to
2.57 days), moderate quality of evidence; and peak blood alcohol concentration
(BAC) (SMD -0.14; 95% CI -0.23 to -0.05 or a decrease in peak BAC from 0.144% to
0.129%), moderate quality of evidence. A marginal effect was found for alcohol
problems (SMD -0.08; 95% CI -0.15 to 0.00 or a reduction in an alcohol problems
scale score from 8.91 to 8.18), low quality of evidence. No effects were found
for binge drinking (SMD -0.05; 95% CI -0.12 to 0.01), moderate quality of
evidence; or average BAC (SMD -0.08; 95% CI -0.22 to 0.06), moderate quality of
evidence. We also considered other outcomes and at four or more months follow-up
we found no effects on drink-driving (SMD -0.11; 95% CI -0.31 to 0.09), moderate
quality of evidence; or other alcohol-related risky behaviour (SMD -0.14; 95% CI
0.30 to 0.02), moderate quality of evidence.Further analyses showed that the type
of control comparison (assessment only versus alternative intervention) did not
predict the outcome in a clear or straightforward way; and there was no
consistent relationship between the duration of the MI intervention (in minutes)
and effect size. AUTHORS' CONCLUSIONS: The results of this review indicate that
there are no substantive, meaningful benefits of MI interventions for the
prevention of alcohol misuse. Although some significant effects were found, we
interpret the effect sizes as being too small, given the measurement scales used
in the studies included in the review, to be of relevance to policy or practice.
Moreover, the statistically significant effects are not consistent for all misuse
measures, heterogeneity was a problem in some analyses and bias cannot be
discounted as a potential cause of these findings.
PMID- 25140981
TI - An empirical study of alcohol consumption by patients considering HCV treatment.
AB - BACKGROUND: Alcohol accelerates the course of hepatitis C (HCV) infection and
liver damage. Little is known about recency of alcohol use among patients with
HCV. OBJECTIVES: Alcohol consumption recency was compared among HCV patients with
and without alcohol use disorders and current and lifetime alcohol use histories.
METHODS: Patients considering antiviral treatment for HCV (n = 309) recruited
from university-affiliated and VA liver and infectious disease clinics were
assessed for lifetime and current-year psychiatric disorders and alcohol-use
patterns. Full diagnostic interviews, self-report surveys, medical record review,
and urine screening for recent alcohol and drug use were conducted. RESULTS: 60%
used alcohol in the last year. Besides alcohol history, those who stopped using
alcohol in the past year differed from those with no lifetime use only in gender
(60% vs. 22%); however, patients no longer using alcohol in the last year were
less likely than those still using to have a current drug use disorder (16% vs.
3%) or last-month drug use (52% vs. 30%), and had fewer current risky behaviors
(1.3 vs. 0.6). Among patients with last-year alcohol use, those with past alcohol
use disorders differed from those without only by higher prevalence of drug use
disorder (84% vs. 47%) and drug use after HCV diagnosis (67% vs. 43%).
CONCLUSIONS: Patients who had stopped using alcohol for at least a year were much
like those who never used alcohol in regard to other drug use, psychiatric
history, smoking, and risky behaviors. These findings indicate that HCV patients
with at least a year of abstinence from alcohol, including those with a history
of alcohol use disorder, should be considered HCV treatment candidates.
PMID- 25140982
TI - Orthopedic surgery in ancient Egypt.
AB - BACKGROUND: Ancient Egypt might be considered the cradle of medicine. The modern
literature is, however, sometimes rather too enthusiastic regarding the
procedures that are attributed an Egyptian origin. I briefly present and analyze
the claims regarding orthopedic surgery in Egypt, what was actually done by the
Egyptians, and what may have been incorrectly ascribed to them. METHODS: I
reviewed the original sources and also the modern literature regarding surgery in
ancient Egypt, concentrating especially on orthopedic surgery. RESULTS: As is
well known, both literary sources and the archaeological/osteological material
bear witness to treatment of various fractures. The Egyptian painting, often
claimed to depict the reduction of a dislocated shoulder according to Kocher's
method, is, however, open to interpretation. Therapeutic amputations are never
depicted or mentioned in the literary sources, while the specimens suggested to
demonstrate such amputations are not convincing. INTERPRETATION: The ancient
Egyptians certainly treated fractures of various kinds, and with varying degrees
of success. Concerning the reductions of dislocated joints and therapeutic
amputations, there is no clear evidence for the existence of such procedures. It
would, however, be surprising if dislocations were not treated, even though they
have not left traces in the surviving sources. Concerning amputations, the
general level of Egyptian surgery makes it unlikely that limb amputations were
done, even if they may possibly have been performed under extraordinary
circumstances.
PMID- 25140983
TI - Osteoarthritis treatment using autologous conditioned serum after placebo.
AB - BACKGROUND AND PURPOSE: Autologous conditioned serum (ACS) is a disease-modifying
drug for treatment of knee osteoarthritis, and modest superiority over placebo
was reported in an earlier randomized controlled trial (RCT). We hypothesized
that when given the opportunity, placebo-treated patients from that RCT would now
opt for ACS treatment, which would result in a greater clinical improvement than
placebo. METHODS: Of 74 patients treated with placebo in the previous trial, 20
opted for ACS treatment. Patients who did not choose further treatment were
interviewed about their reasons. Clinical improvement of the 20 ACS-treated
patients was measured using knee-specific clinical scores, as was "response
shift" at 3 and 12 months. RESULTS: In the 20 patients who did opt for ACS, the
visual analog scale (VAS) score for pain improved; but after 12 months, clinical
results were similar to those after placebo treatment. Response shift measurement
demonstrated that the 20 patients had adapted to their disabilities during
treatment. INTERPRETATION: Placebo-treated patients from an earlier trial were
reluctant to undergo ACS treatment, in part due to the laborious nature of the
therapy. In a subset of patients who opted for treatment, ACS treatment after
placebo did not result in greater clinical improvement than placebo treatment
only. However, due to the limited power of the current study and possible
selection bias, definite advice on using or refraining from ACS cannot be given.
PMID- 25140984
TI - Computer-assisted surgery in orthopedic oncology.
AB - BACKGROUND AND PURPOSE: In orthopedic oncology, computer-assisted surgery (CAS)
can be considered an alternative to fluoroscopy and direct measurement for
orientation, planning, and margin control. However, only small case series
reporting specific applications have been published. We therefore describe
possible applications of CAS and report preliminary results in 130 procedures.
PATIENTS AND METHODS: We conducted a retrospective cohort study of all
oncological CAS procedures in a single institution from November 2006 to March
2013. Mean follow-up time was 32 months. We categorized and analyzed 130
procedures for clinical parameters. The categories were image-based intralesional
treatment, image-based resection, image-based resection and reconstruction, and
imageless resection and reconstruction. RESULTS: Application to intralesional
treatment showed 1 inadequate curettage and 1 (other) recurrence in 63 cases.
Image-based resections in 42 cases showed 40 R0 margins; 16 in 17 pelvic
resections. Image-based reconstruction facilitated graft creation with a mean
reconstruction accuracy of 0.9 mm in one case. Imageless CAS was helpful in
resection planning and length- and joint line reconstruction for tumor
prostheses. INTERPRETATION: CAS is a promising new development. Preliminary
results show a high number of R0 resections and low short-term recurrence rates
for curettage.
PMID- 25140985
TI - Metallosis and elevated serum levels of tantalum following failed revision hip
arthroplasty--a case report.
PMID- 25140986
TI - Wear of a sequentially annealed polyethylene acetabular liner.
AB - BACKGROUND AND PURPOSE: We previously reported on a randomized controlled trial
(RCT) that examined the effect of adding tobramycin to bone cement after femoral
stem migration. The present study examined femoral head penetration into both
conventional and highly crosslinked polyethylene acetabular liners in the same
group of RCT patients, with a minimum of 5 years of postoperative follow-up.
PATIENTS AND METHODS: Linear penetration of the femoral head into an X3 (Stryker)
crosslinked polyethylene (XLPE) liner was measured in 18 patients (19 hips) using
radiostereometric analysis (RSA). Femoral head penetration was also measured in 6
patients (6 hips) with a conventional polyethylene liner (CPE), which served as a
control group. RESULTS: The median proximal femoral head penetration in the XLPE
group after 5.5 years was 0.025 mm with a steady-state penetration rate of 0.001
mm/year between year 1 and year 5. The CPE liner showed a median proximal head
penetration of 0.274 mm after 7.2 years, at a rate of 0.037 mm/year.
INTERPRETATION: The Trident X3 sequentially annealed XLPE liner shows excellent
in vivo wear resistance compared to non-crosslinked CPE liners at medium-term
implantation. The rate of linear head penetration in the XLPE liners after > 5
years of follow-up was 0.001 mm/year, which is in close agreement with the
results of previous studies.
PMID- 25140987
TI - Sequence of the Essex-Lopresti lesion--a high-speed video documentation and
kinematic analysis.
PMID- 25140988
TI - A biochemical study of the distribution of collagen and its crosslinks in knee
ligaments and the patellar tendon.
AB - PURPOSE: The purpose of this study was to investigate biochemical differences in
collagen crosslinks from different locations within the ligaments and a tendon of
the human knee. MATERIALS AND METHODS: The anterior cruciate ligament (ACL),
posterior cruciate ligament (PCL), medial collateral ligament (MCL), lateral
collateral ligament (LCL), and patellar tendon (PT) were obtained from 24
cadavers (13 men and 11 women) whose average age at the time of death was 84.8
years. Ligaments and PT samples were obtained from the femoral and tibial
insertions and the midsubstance. Hydroxyproline (Hyp) and collagen crosslinks,
including pyridinoline (Pyr) and pentosidine (Pen), were compared among the
different sites. RESULTS: The midsubstance Hyp concentration was greater than at
the femoral and tibial insertions in the ACL (p = 0.00124 and 0.000255,
respectively) and PCL (p = 0.00036 and 0.042, respectively). The Pyr:collagen
ratio did not differ among sites in any of the ligaments or PT. The Pen:collagen
ratio at the midsubstance was greater than at the femoral and tibial insertions
in the ACL (p = 0.00022 and 0.00025, respectively) and LCL (p = 0.000081 and
0.000021, respectively) and was greater at the femoral insertion in the MCL (p =
0.00010). CONCLUSIONS: The mature collagen crosslink Pyr was not different in
distribution in knee ligaments and the PT. Pen increased at the midsubstance
ligaments and the PT. As increased Pen may represent ligament degeneration, this
may indicate that degeneration may progress more rapidly at the midsubstance than
at the insertion sites of a ligament.
PMID- 25140989
TI - Biomaterial-mesenchymal stem cell constructs for immunomodulation in composite
tissue engineering.
AB - Cell-based treatments are being developed as a novel approach for the treatment
of many diseases in an effort to repair injured tissues and regenerate lost
tissues. Interest in the potential use of multipotent progenitor or stem cells
has grown significantly in recent years, specifically the use of mesenchymal stem
cells (MSCs), for tissue engineering in combination with extracellular matrix
based scaffolds. An area that warrants further attention is the local or systemic
host responses toward the implanted cell-biomaterial constructs. Such
immunological responses could play a major role in determining the clinical
efficacy of the therapeutic device or biomaterials used. MSCs, due to their
unique immunomodulatory properties, hold great promise in tissue engineering as
they not only directly participate in tissue repair and regeneration but also
modulate the host foreign body response toward the engineered constructs. The
purpose of this review was to summarize the current state of knowledge and
applications of MSC-biomaterial constructs as a potential immunoregulatory tool
in tissue engineering. Better understanding of the interactions between
biomaterials and cells could translate to the development of clinically relevant
and novel cell-based therapeutics for tissue reconstruction and regenerative
medicine.
PMID- 25140990
TI - Boron dipyrromethene as a fluorescent caging group for single-photon uncaging
with long-wavelength visible light.
AB - Caged compounds are useful tools for precise spatiotemporal modulation of cell
functions, but in most cases uncaging requires ultraviolet (UV) light, which is
cytotoxic and has limited tissue penetration. Therefore, caged compounds that can
be activated by longer-wavelength light are required. Here we describe a novel
photoelimination reaction of 4-aryloxy boron dipyrromethene (BODIPY) derivatives
and show that BODIPY can function as a caging group for phenol groups. We
developed a novel BODIPY-caged histamine compound, which is photoactivatable with
blue-green visible light to stimulate cultured HeLa cells in a spatiotemporally
well-controlled manner. This caging strategy is expected to be widely applicable
to develop tools for probing various cellular functions.
PMID- 25140991
TI - Tandem ring-closing metathesis/transfer hydrogenation: practical chemoselective
hydrogenation of alkenes.
AB - An operationally simple chemoselective transfer hydrogenation of alkenes using
ruthenium metathesis catalysts is presented. Of great practicality, the transfer
hydrogenation reagents can be added directly to a metathesis reaction and effect
hydrogenation of the product alkene in a single pot at ambient temperature
without the need to seal the vessel to prevent hydrogen gas escape. The reduction
is applicable to a range of alkenes and can be performed in the presence of aryl
halides and benzyl groups, a notable weakness of Pd-catalyzed hydrogenations.
Scope and mechanistic considerations are presented.
PMID- 25140992
TI - Profile hidden Markov models for the detection of viruses within metagenomic
sequence data.
AB - Rapid, sensitive, and specific virus detection is an important component of
clinical diagnostics. Massively parallel sequencing enables new diagnostic
opportunities that complement traditional serological and PCR based techniques.
While massively parallel sequencing promises the benefits of being more
comprehensive and less biased than traditional approaches, it presents new
analytical challenges, especially with respect to detection of pathogen sequences
in metagenomic contexts. To a first approximation, the initial detection of
viruses can be achieved simply through alignment of sequence reads or assembled
contigs to a reference database of pathogen genomes with tools such as BLAST.
However, recognition of highly divergent viral sequences is problematic, and may
be further complicated by the inherently high mutation rates of some viral types,
especially RNA viruses. In these cases, increased sensitivity may be achieved by
leveraging position-specific information during the alignment process. Here, we
constructed HMMER3-compatible profile hidden Markov models (profile HMMs) from
all the virally annotated proteins in RefSeq in an automated fashion using a
custom-built bioinformatic pipeline. We then tested the ability of these viral
profile HMMs ("vFams") to accurately classify sequences as viral or non-viral.
Cross-validation experiments with full-length gene sequences showed that the
vFams were able to recall 91% of left-out viral test sequences without
erroneously classifying any non-viral sequences into viral protein clusters.
Thorough reanalysis of previously published metagenomic datasets with a set of
the best-performing vFams showed that they were more sensitive than BLAST for
detecting sequences originating from more distant relatives of known viruses. To
facilitate the use of the vFams for rapid detection of remote viral homologs in
metagenomic data, we provide two sets of vFams, comprising more than 4,000 vFams
each, in the HMMER3 format. We also provide the software necessary to build
custom profile HMMs or update the vFams as more viruses are discovered
(http://derisilab.ucsf.edu/software/vFam).
PMID- 25140993
TI - Iodoaromatization reactions of enyne-dioxinones: syntheses of 4H-1,3-benzodioxin
4-ones, masked pentasubstituted arenes.
AB - Sequential reaction of a keto-dioxinone with dimethylformamide dimethyl acetal
and a range of magnesium acetylides gave the corresponding enyne-dioxinones as
mixtures of E and Z isomers (E > Z). Subsequent reaction with iodine monochloride
resulted in cycloaromatization, presumably via an iodovinyl cation, giving a
range of 4H-1,3-benzodioxin-4-ones.
PMID- 25140994
TI - Thyroid function and metabolic risk factors in obese youth. Changes during follow
up: a preventive mechanism?
AB - OBJECTIVES: High TSH levels often observed in overweight subjects are associated
with metabolic risk. Thyroid hormones which are involved in fat and carbohydrates
metabolism are more rarely studied; their blood levels were measured to more
precisely explain the relationships between thyroid function and obesity, in
healthy overweight youth. This correlation was studied at baseline and during
follow-up of some patients. MATERIALS/METHODS: Data collected were BMI and BMI z
score, thyroid hormones (TSH, fT4, fT3), fasting blood glucose, HOMA-IR, lipids
(triglycerides, HDL and LDL cholesterol), transaminase activity, fibrinogen,
leptin, IGF-I; body composition (biphotonic absorptiometry). Data collected in a
sample of the group after 6-18 months of medical intervention could also be
studied. RESULTS: At baseline, 13% of the 528 obese subjects (55% girls; 11.3+/
2.4 years, range 4.1-17.9; BMI z score: 5.4+/-2.4) had TSH>4mUI/l; fT3 levels
were associated with age and transaminase activity; using multivariate regression
analysis, with z-score and age as covariates, fT4 showed correlations with TSH,
insulin, HOMA IR, blood lipids, and fibrinogen. No correlations were found with
leptin, iodine excretion, IGF-I.In 79 patients followed for 52+/-15 wk (45%
girls; age range 8-18.3 years), univariate regression showed a positive
correlation between changes in TSH and HOMA-IR, and between changes in fT4 and
HDL. Multivariate regression analysis with z score as covariate showed that
baseline TSH was associated with negative changes in HOMA-IR. CONCLUSIONS:
Increased TSH may be predictive of a decrease in insulin resistance, it should be
measured with thyroid hormones; fT4 was associated with a low metabolic risk.
Changes in thyroid function could protect against the occurrence of obesity
associated metabolic diseases.
PMID- 25140995
TI - A 6-year follow-up of a randomized prospective trial comparing methimazole
treatment with or without exogenous L-thyroxine in Chinese patients with Graves'
disease.
AB - OBJECTIVE: Antithyroid drug therapy is one of the main medical treatments for
Graves' disease. There have been conflicting reports as to whether the addition
of exogenous L-thyroxine improves remission rates more than antithyroid drugs
alone. This randomized, controlled and prospective clinical trial was undertaken
to investigate the long-term outcome of methimazole treatment with or without
exogenous L-thyroxine in Chinese patients. METHODS: 145 patients with Graves'
disease were randomly divided into 3 groups and all patients initially received
30 mg of methimazole daily for at least 1 month and then followed the titration
regimen with or without L-thyroxine: group 1 (30 mg->20 mg->15 mg->10 mg->5 mg);
group 2 (30 mg->20 mg->15 mg->10 mg+L-thyroxine->5 mg+L-thyroxine); group 3 (30
mg->20 mg->15 mg->10 mg+L-thyroxine->5 mg+L-thyroxine->2.5 mg+L-thyroxine). The
drug therapy was discontinued after 5 months of the final dose. RESULTS: 16 out
of 46 patients in group 1 (34.8%), 12 out of 47 in group 2 (25.5%) and 16 out of
52 in group 3 (30.8%) had a recurrence of Graves' disease within 6-year follow-up
after drug withdrawal. Survival Analysis showed no significant differences in the
remission rates between any 2 groups, despite the remission rates in group 2 and
3 were slightly higher than that in group 1. CONCLUSIONS: The addition of L
thyroxine to methimazole treatment in patients with Graves' disease neither
improves nor prevents the remission or recurrence of Graves' disease in China.
PMID- 25140996
TI - Serum concentration of VEGF and PDGF-AA in patients with active thyroid
orbitopathy before and after immunosuppressive therapy.
AB - INTRODUCTION: Thyroid orbitopathy (TO) is the most frequent extrathyroid
manifestation of Graves' disease. The aim of this study was to evaluate the serum
concentration of Vascular Endothelial Growth Factor (VEGF), Plated-Derived Growth
Factor-AA (PDGF-AA) in the blood of patients with active OT before and after
immunosuppressive therapy. PATIENTS AND METHODS: The study was performed in group
of 39 patients with clinically active TO (Group A) in euthyroid (n=18, Group A I)
and hyperthyroid (n=21, Group A II) stage of Graves' disease in moderate or
severe stage of TO. Control group consist of 20 healthy age-matched control
subjects. Concentration of studied proangiogenic factors in serum samples were
measured by an enzyme linked immunosorbent assay (ELISA) before (group A) and
after (group A1) intensive pulse methylprednisolone treatment and one month after
the end of additional oral methylprednisolone treatment (Group A2). RESULTS: We
have found significant increased serum levels of VEGF in patients with TO (reg
ardless to treatment) when compared with control group (542.4+/-328.1 pg/ml vs.
94.6+/-55.3 pg/ml, p=0.0002) and increased serum levels of -PDGF-AA in patients
before treatment (3 173.6+/-1 480.3 pg/ml) in comparison with controls (1 768.9+/
520.0 pg/ml) and patients after intensive pulse methyloprednisolone treatment (2
325.9+/-1 456.8 pg/ml). One month after the end of additional oral
methylprednisolone treatment (Group A2) concentration of PDGF-AA still decreased
and were was not significant difference with value in control group (1 853.1+/
795.4 vs. 1 769.9+/-520.0 pg/ml, p=0.99). Serum concentration of VEGF was still
significantly higher compared with control. We have not observed difference in
serum concentration of studied proangiogenic factors between patients in
euthyroid or hyperthyroid stage of Graves' disease. CONCLUSIONS: RESULTS of the
present study confirm the fact that angiogenesis could play a role in
pathogenesis of thyroid orbitopathy.
PMID- 25140997
TI - The GLP-1 analogue liraglutide protects cardiomyocytes from high glucose-induced
apoptosis by activating the Epac-1/Akt pathway.
AB - BACKGROUND: Cardiomyocyte apoptosis is closely related to cardiac dysfunction in
diabetic patients. Although GLP-1 analogs are used as anti-diabetic drugs, their
effects on cardiomyocytes remain unclear. The aim of this study was to assess the
effects of the GLP-1 analog liraglutide on high glucose-induced cardiomyocyte
apoptosis. METHODS: Wistar rats were divided into normal (N), diabetes mellitus
(DM), and liraglutide (LIR) groups. H9c2 cardiomyocytes were divided into normal
(NG) and high glucose (HG) groups, 4 liraglutide groups (Lir1-4), 3 Epac-1
agonist intervention groups (CPT1-3), and 2 Epac-1 shRNA transfection groups
(sh21 and sh22). Apoptosis was measured using TUNEL assays, and the apoptotic
indices were calculated. Intracellular ROS levels were measured using a DCFH-DA
probe. Epac-1, Akt, and P-Akt (Ser473) expression were measured by
immunoblotting. RESULTS: The apoptotic index and intracellular ROS levels were
higher in the HG than NG group (P<0.01). Liraglutide decreased both parameters in
a dose- and time-dependent manner. Liraglutide increased the expression of Epac-1
in the myocardium of diabetic rats and H9c2 cells (P<0.05), and increased Akt
phosphorylation in the myocardium of diabetic rats (P<0.05). Liraglutide
treatment also increased the P-Akt (Ser473)/Akt ratio (P<0.05). An Epac-1 agonist
increased Epac-1 expression (P<0.05) and the P-Akt (Ser473)/Akt ratio (P<0.05) in
a dose-dependent manner, and subsequently decreased apoptosis and intracellular
ROS. Conversely, Epac-1shRNA knocked-down Epac-1 expression (P<0.01) and
decreased the P-Akt (Ser473)/Akt ratio (P<0.05), but had no effect on apoptosis
and intracellular ROS levels. CONCLUSIONS: Liraglutide protects cardiomyocytes
from high glucose-induced apoptosis by activating the Epac-1/Akt pathway.
PMID- 25140998
TI - Chimpanzees and humans mimic pupil-size of conspecifics.
AB - Group-living typically provides benefits to individual group members but also
confers costs. To avoid incredulity and betrayal and allow trust and cooperation,
individuals must understand the intentions and emotions of their group members.
Humans attend to other's eyes and from gaze and pupil-size cues, infer
information about the state of mind of the observed. In humans, pupil-size tends
to mimic that of the observed. Here we tested whether pupil-mimicry exists in our
closest relative, the chimpanzee (P. troglodytes). We conjectured that if pupil
mimicry has adaptive value, e.g. to promote swift communication of inner states
and facilitate shared understanding and coordination, pupil-mimicry should emerge
within but not across species. Pupillometry data was collected from human and
chimpanzee subjects while they observed images of the eyes of both species with
dilating/constricting pupils. Both species showed enhanced pupil-mimicry with
members of their own species, with effects being strongest in humans and
chimpanzee mothers. Pupil-mimicry may be deeply-rooted, but probably gained
importance from the point in human evolution where the morphology of our eyes
became more prominent. Humans' white sclera surrounding the iris, and the fine
muscles around their eyes facilitate non-verbal communication via eye signals.
PMID- 25140999
TI - An early warning system based on syndromic surveillance to detect potential
health emergencies among migrants: results of a two-year experience in Italy.
AB - Profound geopolitical changes have impacted the southern and eastern
Mediterranean since 2010 and defined a context of instability that is still
affecting several countries today. Insecurity combined with the reduction of
border controls has led to major population movements in the region and to
migration surges from affected countries to southern Europe, especially to Italy.
To respond to the humanitarian emergency triggered by this migration surge, Italy
implemented a syndromic surveillance system in order to rapidly detect potential
public health emergencies in immigrant reception centres. This system was
discontinued after two years. This paper presents the results of this experience
detailing its strengths and weaknesses in order to document the applicability and
usefulness of syndromic surveillance in this specific context.
PMID- 25141000
TI - Human leptospirosis trends: northeast Thailand, 2001-2012.
AB - The objective of this study was to determine the changing trend of leptospirosis
over time in Thailand using two prospective hospital-based studies conducted
amongst adult patients with acute undifferentiated fever (AUFI) admitted to
Maharat Nakhon Ratchasima Hospital, Nakhon Ratchasima Province, Thailand between
July 2001 to December 2002 and between July 2011 to December 2012. During the
first period, leptospirosis (98 patients, 40%) and scrub typhus (59 patients,
24.1%) were the two major causes of AUFI. In the second period, scrub typhus (137
patients, 28.3%) was found to be more common than leptospirosis (61 patients,
12.7%). Amongst patients with leptospirosis, the proportion of male patients and
the median age were similar. Leptospira interrogans serogroup Autumnalis was the
major infecting serogroup in both study periods. The case fatality rate of
leptospirosis was significantly higher in 2011-2012 as compared with the case
fatality rate in 2001-2002 (19.7% vs. 6.3%, p < 0.001). In summary, we found that
number of leptospirosis cases had decreased over time. This trend is similar to
reportable data for leptospirosis complied from passive surveillance by the
Ministry of Public Health, Thailand. However, the case fatality rate of severe
leptospirosis has increased. Severe lung hemorrhage associated with leptospirosis
remained the major cause of death.
PMID- 25141001
TI - HIV risky sexual behaviors and HIV infection among immigrants: a cross-sectional
study in Lisbon, Portugal.
AB - This study aimed to examine risky sexual behavior, its associated factors and HIV
infection among immigrants. A participatory cross-sectional survey was conducted
with 1187 immigrants at the National Immigrant Support Centre, in Lisbon (52.2%
female; 34.0% Africans, 33.8% Brazilians, 32.2% Eastern Europeans). About 38% of
participants reported >= 2 sexual partners in the previous year, 16.2% both
regular and occasional sexual partners (last 12 months), 33.1% inconsistent
condom use with occasional partners, and 64% no condom use in the last sexual
intercourse. Unprotected sex in the last sexual intercourse was more likely among
women, Africans, those older, with elementary education, those married and those
who didn't receive free condoms in the previous year. No condom use was less
likely among those having only occasional sexual partners and both regular and
occasional sexual partners. One third of participants had never been tested for
HIV. Those never tested reported more frequently inconsistent condom use than
those ever tested. Overall, 2.0% reported being HIV positive (2.5% of men; 4.4%
of Africans); 4.3% admitted having a STI in previous year. HIV-positive
immigrants reported high-risk sexual behaviors. Tailored interventions to promote
awareness of HIV serostatus among immigrants as well as culturally adapted risk
reduction strategies should be strengthened.
PMID- 25141002
TI - Histological lesions, cell cycle arrest, apoptosis and T cell subsets changes of
spleen in chicken fed aflatoxin-contaminated corn.
AB - The purpose of this study was to evaluate the effects of corn naturally
contaminated with aflatoxin B1 and aflatoxin B2 on pathological lesions,
apoptosis, cell cycle phases and T lymphocyte subsets of spleen, and to provide
an experimental basis for understanding the mechanism of aflatoxin-induced
immunosuppression. A total of 900 COBB500 male broilers were randomly allocated
into five groups with six replicates per group and 30 birds per replicate. The
experiment lasted for 6 weeks and the five dietary treatments consisted of
control, 25% contaminated corn, 50% contaminated corn, 75% contaminated corn and
100% contaminated corn groups. The histopathological spleen lesions from the
contaminated corn groups was characterized as congestion of red pulp, increased
necrotic cells and vacuoles in the splenic corpuscle and periarterial lymphatic
sheath. The contaminated corn intake significantly increased relative weight of
spleen, percentages of apoptotic splenocytes, induced cell cycle arrest of
splenocytes, increased the percentages of CD3+CD8+ T cells and decreased the
ratios of CD3+CD4+ to CD3+CD8+. The results suggest that AFB-induced
immunosuppression maybe closely related to the lesions of spleen.
PMID- 25141003
TI - Influence of surfactant and lipid type on the physicochemical properties and
biocompatibility of solid lipid nanoparticles.
AB - Nine types of solid lipid nanoparticle (SLN) formulations were produced using
tripalmitin (TPM), glyceryl monostearate (GM) or stearic acid (SA), stabilized
with lecithin S75 and polysorbate 80. Formulations were prepared presenting PI
values within 0.25 to 0.30, and the physicochemical properties, stability upon
storage and biocompatibility were evaluated. The average particle size ranged
from 116 to 306 nm, with a negative surface charge around -11 mV. SLN presented
good stability up to 60 days. The SLN manufactured using SA could not be measured
by DLS due to the reflective feature of this formulation. However, TEM images
revealed that SA nanoparticles presented square/rod shapes with an approximate
size of 100 nm. Regarding biocompatibility aspects, SA nanoparticles showed
toxicity in fibroblasts, causing cell death, and produced high hemolytic rates,
indicating toxicity to red blood cells. This finding might be related to lipid
type, as well as, the shape of the nanoparticles. No morphological alterations
and hemolytic effects were observed in cells incubated with SLN containing TPM
and GM. The SLN containing TPM and GM showed long-term stability, suggesting good
shelf-life. The results indicate high toxicity of SLN prepared with SA, and
strongly suggest that the components of the formulation should be analyzed in
combination rather than separately to avoid misinterpretation of the results.
PMID- 25141005
TI - Insertions or deletions (Indels) in the rrn 16S-23S rRNA gene internal
transcribed spacer region (ITS) compromise the typing and identification of
strains within the Acinetobacter calcoaceticus-baumannii (Acb) complex and
closely related members.
AB - To determine whether ITS sequences in the rrn operon are suitable for identifying
individual Acinetobacter Acb complex members, we analysed length and sequence
differences between multiple ITS copies within the genomes of individual strains.
Length differences in ITS reported previously between A. nosocomialis BCRC15417T
(615 bp) and other strains (607 bp) can be explained by presence of an insertion
(indel 13i/1) in the longer ITS variant. The same Indel 13i/1 was also found in
ITS sequences of ten strains of A. calcoaceticus, all 639 bp long, and the 628 bp
ITS of Acinetobacter strain BENAB127. Four additional indels (13i/2-13i/5) were
detected in Acinetobacter strain c/t13TU 10090 ITS length variants (608, 609,
620, 621 and 630 bp). These ITS variants appear to have resulted from horizontal
gene transfer involving other Acinetobacter species or in some cases unrelated
bacteria. Although some ITS copies in strain c/t13TU 10090 are of the same length
(620 bp) as those in Acinetobacter strains b/n1&3, A. pittii (10 strains), A.
calcoaceticus and A. oleivorans (not currently acknowledged as an Acb member),
their individual ITS sequences differ. Thus ITS length by itself can not by
itself be used to identify Acb complex strains. A shared indel in ITS copies in
two separate Acinetobacter species compromises the specificity of ITS targeted
probes, as shown with the Aun-3 probe designed to target the ITS in A. pitti. The
presence of indel 13i/5 in the ITS of Acinetobacter strain c/t13TU means it too
responded positively to this probe. Thus, neither ITS sequencing nor the
currently available ITS targeted probes can distinguish reliably between Acb
member species.
PMID- 25141004
TI - A novel zebrafish model to provide mechanistic insights into the inflammatory
events in carrageenan-induced abdominal edema.
AB - A suitable small animal model may help in the screening and evaluation of new
drugs, especially those from natural products, which can be administered at lower
dosages, fulfilling an urgent worldwide need. In this study, we explore whether
zebrafish could be a model organism for carrageenan-induced abdominal edema. The
research results showed that intraperitoneal (i.p.) administration of 1.5% lambda
carrageenan in a volume of 20 uL significantly increased abdominal edema in adult
zebrafish. Levels of the proinflammatory proteins tumor necrosis factor-alpha
(TNF-alpha) and inducible nitric oxide synthase (iNOS) were increased in
carrageenan-injected adult zebrafish during the development of abdominal edema.
An associated enhancement was also observed in the leukocyte marker,
myeloperoxidase (MPO). To support these results, we further observed that i.p.
methylprednisolone (MP; 1 ug), a positive control, significantly inhibited
carrageenan-induced inflammation 24 h after carrageenan administration.
Furthermore, i.p. pretreatment with either an anti-TNF-alpha antibody (1?5
dilution in a volume of 20 uL) or the iNOS-selective inhibitor aminoguanidine
(AG; 1 ug) inhibited carrageenan-induced abdominal edema in adult zebrafish. This
new animal model is uncomplicated, easy to develop, and involves a
straightforward inducement of inflammatory edema for the evaluation of small
volumes of drugs or test compounds.
PMID- 25141006
TI - A robust and adaptable high throughput screening method to study host-microbiota
interactions in the human intestine.
AB - The intestinal microbiota has many beneficial roles for its host. However, the
precise mechanisms developed by the microbiota to influence the host intestinal
cell responses are only partially known. The complexity of the ecosystem and our
inability to culture most of these micro-organisms have led to the development of
molecular approaches such as functional metagenomics, i.e. the heterologous
expression of a metagenome in order to identify functions. This elegant strategy
coupled to high throughput screening allowed to identify novel enzymes from
different ecosystems where culture methods have not yet been adapted to isolate
the candidate microorganisms. We have proposed to use this functional metagenomic
approach in order to model the microbiota's interaction with the host by
combining this heterologous expression with intestinal reporter cell lines. The
addition of the cellular component to this functional metagenomic approach
introduced a second important source of variability resulting in a novel
challenge for high throughput screening. First attempts of high throughput
screening with various reporter cell-lines showed a high distribution of the
response and consequent difficulties to reproduce the response, impairing an easy
and clear identification of confirmed hits. In this study, we developed a robust
and reproducible methodology to combine these two biological systems for high
throughput application. We optimized experimental setups and completed them by
appropriate statistical analysis tools allowing the use this innovative approach
in a high throughput manner and on a broad range of reporter assays. We herewith
present a methodology allowing a high throughput screening combining two
biological systems. Therefore ideal conditions for homogeneity, sensitivity and
reproducibility of both metagenomic clones as well as reporter cell lines have
been identified and validated. We believe that this innovative method will allow
the identification of new bioactive microbial molecules and, subsequently, will
promote understanding of host-microbiota interactions.
PMID- 25141007
TI - Ant-plant interaction in a tropical savanna: may the network structure vary over
time and influence on the outcomes of associations?
AB - Plant-animal interactions occur in a community context of dynamic and complex
ecological interactive networks. The understanding of who interacts with whom is
a basic information, but the outcomes of interactions among associates are
fundamental to draw valid conclusions about the functional structure of the
network. Ecological networks studies in general gave little importance to know
the true outcomes of interactions and how they may change over time. We evaluate
the dynamic of an interaction network between ants and plants with extrafloral
nectaries, by verifying the temporal variation in structure and outcomes of
mutualism for the plant community (leaf herbivory). To reach this goal, we used
two tools: bipartite network analysis and experimental manipulation. The networks
exhibited the same general pattern as other mutualistic networks: nestedness,
asymmetry and low specialization and this pattern was maintained over time, but
with internal changes (species degree, connectance and ant abundance). These
changes influenced the protection effectiveness of plants by ants, which varied
over time. Our study shows that interaction networks between ants and plants are
dynamic over time, and that these alterations affect the outcomes of mutualisms.
In addition, our study proposes that the set of single systems that shape
ecological networks can be manipulated for a greater understanding of the entire
system.
PMID- 25141008
TI - A pilot study of serum microRNAs panel as potential biomarkers for diagnosis of
nonalcoholic fatty liver disease.
AB - BACKGROUND: The invasive nature of liver biopsy makes the histopathological
diagnosis of non-alcoholic fatty liver disease (NAFLD) difficult and its
diagnostic performance unsatisfactory. The present study aimed to identify a
serum microRNA (miRNA) expression profile that could serve as a novel diagnostic
biomarker for NAFLD. METHODS: Serum miRNA expression was investigated using three
cohorts comprising 465 participants (healthy controls and NAFLD patients)
recruited between August 2010 and June 2013. miRNA expression was initially
screened by Illumina sequencing using serum samples pooled from 20 patients and
20 controls. Quantitative reverse transcriptase polymerase chain reaction assay
was then used to evaluate the expression of selected miRNAs. A logistic
regression model was constructed using a training cohort (n = 242) and validated
using another cohort (n = 183). The area under the receiver operating
characteristic curve (AUC) was used to evaluate diagnostic accuracy. RESULTS: We
identified an miRNA panel (hsa-miR-122-5p, hsa-miR-1290, hsa-miR-27b-3p, and hsa
miR-192-5p) with a high diagnostic accuracy for NAFLD. The satisfactory
diagnostic performance of the miRNA panel remained regardless of the NAFLD
activity score (NAS) status. There was significant difference between the AUC
values of the miRNA panel and those of ALT (AUC = 0.786, 95% CI = 0.717-0.855; P
= 0.142) and FIB-4 (AUC = 0.795, 95% CI = 0.730-0.860; sensitivity = 69.9%,
specificity = 83.7%. CONCLUSION: We identified a serum microRNA panel with
considerable clinical value in NAFLD diagnosis. The results indicate that the
miRNA panel is a more sensitive and specific biomarker for NAFLD than ALT and FIB
4.
PMID- 25141009
TI - IL-17A induces Pendrin expression and chloride-bicarbonate exchange in human
bronchial epithelial cells.
AB - The epithelium plays an active role in the response to inhaled pathogens in part
by responding to signals from the immune system. Epithelial responses may include
changes in chemokine expression, increased mucin production and antimicrobial
peptide secretion, and changes in ion transport. We previously demonstrated that
interleukin-17A (IL-17A), which is critical for lung host defense against
extracellular bacteria, significantly raised airway surface pH in vitro, a
finding that is common to a number of inflammatory diseases. Using microarray
analysis of normal human bronchial epithelial (HBE) cells treated with IL-17A, we
identified the electroneutral chloride-bicarbonate exchanger Pendrin (SLC26A4) as
a potential mediator of this effect. These data were verified by real-time,
quantitative PCR that demonstrated a time-dependent increase in Pendrin mRNA
expression in HBE cells treated with IL-17A up to 48 h. Using immunoblotting and
immunofluorescence, we confirmed that Pendrin protein expression is increased in
IL-17 treated HBE cells and that it is primarily localized to the mucosal surface
of the cells. Functional studies using live-cell fluorescence to measure
intracellular pH demonstrated that IL-17A induced chloride-bicarbonate exchange
in HBE cells that was not present in the absence of IL-17A. Furthermore, HBE
cells treated with short interfering RNA against Pendrin showed substantially
reduced chloride-bicarbonate exchange. These data suggest that Pendrin is part of
IL-17A-dependent epithelial changes and that Pendrin may therefore be a
therapeutic target in IL-17A-dependent lung disease.
PMID- 25141011
TI - A systematic review on the development of asthma and allergic diseases in
relation to international immigration: the leading role of the environment
confirmed.
AB - BACKGROUND: The prevalence of asthma and allergic diseases is rising worldwide.
Evidence on potential causal pathways of asthma and allergies is growing, but
findings have been contradictory, particularly on the interplay between allergic
diseases and understudied social determinants of health like migration status.
This review aimed at providing evidence for the associat